PMID- 28427173
TI  - Circumvent the uncertainty in the applications of transcriptional signatures to
      tumor tissues sampled from different tumor sites.
AB  - The expression measurements of thousands of genes are correlated with the
      proportions of tumor epithelial cell (PTEC) in clinical samples. Thus, for a
      tumor diagnostic or prognostic signature based on a summarization of expression
      levels of the signature genes, the risk score for a patient may dependent on the
      tumor tissues sampled from different tumor sites with diverse PTEC for the same
      patient. Here, we proposed that the within-samples relative expression orderings
      (REOs) based gene pairs signatures should be insensitive to PTEC variations.
      Firstly, by analysis of paired tumor epithelial cell and stromal cell
      microdissected samples from 27 cancer patients, we showed that above 80% of gene
      pairs had consistent REOs between the two cells, indicating these REOs would be
      independent of PTEC in cancer tissues. Then, by simulating tumor tissues with
      different PTEC using each of the 27 paired samples, we showed that about 90% REOs
      of gene pairs in tumor epithelial cells were maintained in tumor samples even
      when PTEC decreased to 30%. Especially, the REOs of gene pairs with larger
      expression differences in tumor epithelial cells tend to be more robust against
      PTEC variations. Finally, as a case study, we developed a gene pair signature
      which could robustly distinguish colorectal cancer tissues with various PTEC from
      normal tissues. We concluded that the REOs-based signatures were robust against
      PTEC variations.

PMID- 28427172
TI  - The amelioration of cartilage degeneration by photo-crosslinked GelHA hydrogel
      and crizotinib encapsulated chitosan microspheres.
AB  - The present study aimed to investigate the synergistic therapeutic effect of
      decreaseing cartilage angiogenesis via exposure to crizotinib encapsulated by
      chitosan microspheres and photo-crosslinked hydrogel, with the goal of evaluating
      crizotinib as a treatment for osteoarthritis. First, we developed and evaluated
      the characteristics of hydrogels and chitosan microspheres. Next, we measured the
      effect of crizotinib on the cartilage degeneration induced by interleukin-1beta
      in chondrocytes. Crizotinib ameliorated the pathological changes induced by
      interleukin-1beta via its anti-angiogenesis function. In addition, we surgically
      induced osteoarthritis in mice, which were then injected intra-articularly with
      crizotinib-loaded biomaterials. Cartilage matrix degradation, expression of
      vascular endothelial growth factor and extracellular signal-regulated kinases 1/2
      were evaluated after surgery. Treatment with the combination of crizotinib-loaded
      biomaterials retarded the progression of surgically induced osteoarthritis.
      Crizotinib ameliorated cartilage matrix degradation by promoting anti
      angiogenesis and impeding extracellular signal-regulated kinases 1/2 signaling
      pathway. Our results demonstrate that the combination of photo-crosslinked
      hydrogel and crizotinib-loaded chitosan microspheres might represent a promising
      strategy for osteoarthritis treatment.

PMID- 28427176
TI  - Metronomic regimen as an effective treatment for aggressive T-LGL leukemia with
      central nervous system infiltration: clinical experience and review of
      literature.
AB  - A 71-year-old man was diagnosed with T-Large granular lymphocytic (LGL) leukemia,
      which usually represents a relatively indolent clinical course. While the
      clinical manifestation of this patient we report herein was aggressive with
      lasting fever, splenomegaly and hemophagocytic lymphohistiocytosis (HLH). T-cell
      immunophenotype was CD3+CD4-CD8-CD5-CD7-TCRalphabeta+. After comprehensive
      evaluation, an adjusted chemotherapy regimen CEOP (cyclophosphamide, vincristine,
      etoposide, prednisone) with etoposide, a potential effective regimen for HLH was
      administrated to the patient. Although he received intensive regimen, the patient
      showed drug resistance and disease progression with central nervous system (CNS)
      involvement during treatment and showed only transiently response to intrathecal
      methotrexate, cytarabine and dexamethasone. Therefore, considering the refractory
      elderly patient with fragile physical condition, metronomic regimen T-PEPC (oral
      administration of thalidomide, prednisone, cyclophosphamide, etoposide and
      methyhydrazine) was recommended, which refers to the frequent even daily
      administration of cytotoxic drugs at comparatively low doses with minimal or
      prolonged drug-free breaks. The patient responded well to this treatment and
      remained symptom-free for 8-month follow-up. To our knowledge, this is the first
      case of reporting this unique immunophenotype of dual CD4-/CD8- with aggressive
      clinical course and CNS involvement that successfully treated with metronomic
      regimen, suggesting that low dose metronomic regimen could be a better option for
      elderly patient with aggressive T-LGL leukemia.

PMID- 28427178
TI  - Prognostic value of FOXM1 in solid tumors: a systematic review and meta-analysis.
AB  - Accumulated studies have provided controversial evidences of the association
      between Forkhead Box M1 (FOXM1) expression and survival of human solid tumors. To
      address this inconsistency, we performed a meta-analysis with 23 studies
      identified from PubMed and Medline. We found elevated FOXM1-protein expression
      was significantly associated with worse 3-year overall survival (OS) (OR = 3.30,
      95% CI = 2.56 to 4.25, P < 0.00001) 5-year OS (OR =3.35, 95% CI = 2.64 to 4.26, P
      < 0.00001) and 10-year OS (OR = 5.24, 95% CI = 2.61 to 10.52, P < 0.00001) of
      human solid tumors. Similar results were observed when disease free survival
      (DFS) were analyzed. Subgroup analysis showed that FOXM1 overexpression was
      associated with poor prognosis of colorectal cancer, gastric cancer, hepatic
      cancer, lung cancer and ovarian cancer. High expression level of FOXM1 was also
      associated with advanced tumor stage. In conclusion, elevated FOXM1 expression is
      associated with poor survival in most solid tumors. FOXM1 is a potential
      biomarker for prognosis prediction and a promising therapeutic target in human
      solid tumors.

PMID- 28427179
TI  - Comprehensive mapping of the effects of azacitidine on DNA methylation,
      repressive/permissive histone marks and gene expression in primary cells from
      patients with MDS and MDS-related disease.
AB  - Azacitidine (Aza) is first-line treatment for patients with high-risk
      myelodysplastic syndromes (MDS), although its precise mechanism of action is
      unknown. We performed the first study to globally evaluate the epigenetic effects
      of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq),
      DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3
      (ChIP seq). Aza induced a general increase in gene expression with 924
      significantly upregulated genes but this increase showed no correlation with
      changes in DNA methylation or H3K18ac, and only a weak association with changes
      in H3K9me3. Interestingly, we observed activation of transcripts containing 15
      endogenous retroviruses (ERVs) confirming previous cell line studies. DNA
      methylation decreased moderately in 99% of all genes, with a median beta-value
      reduction of 0.018; the most pronounced effects seen in heterochromatin. Aza
      induced hypomethylation correlated significantly with change in H3K9me3. The
      pattern of H3K18ac and H3K9me3 displayed large differences between patients and
      healthy controls without any consistent pattern induced by Aza. We conclude that
      the marked induction of gene expression only partly could be explained by
      epigenetic changes, and propose that activation of ERVs may contribute to the
      clinical effects of Aza in MDS.

PMID- 28427180
TI  - MMP-11 promoted the oral cancer migration and Fak/Src activation.
AB  - Matrix metalloproteinase-11 (MMP-11) has been observed in most invasive human
      carcinomas. The current study investigated the association between the
      clinicopathological characteristics and MMP-11 expression in oral squamous cell
      carcinoma (OSCC) patients. Immunohistochemistry (IHC) staining was performed to
      assess MMP-11 expression in 279 patients with OSCC. In addition, the metastatic
      effects of the MMP-11 overexpression on the OSCC cells were also investigated. We
      found that MMP-11 expression was present in 118/279 (42.3%) cases and expression
      of MMP-11 was associated with higher incidence of lymph node metastasis and worse
      grade of tumor differentiation. Importantly, OSCC patients with strong expression
      of MMP-11 had a significantly lower survival rate (p=0.010). Furthermore, MMP-11
      overexpression in OSCC cells increased in vitro cell migration. Mechanistically,
      MMP-11 increased the cell motility of OSCC cells through focal adhesion
      kinase/Src kinase (FAK/Src) pathway. In conclusion, our results revealed that the
      MMP-11 expression in OSCC samples can predict the progression, especially lymph
      node metastasis, and the survival of OSCC patients in Taiwan.

PMID- 28427181
TI  - Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK.
AB  - Anti-VEGF therapy has been proven to be effective in the treatment of
      pathological angiogenesis. However, therapy resistance often occurs, leading to
      development of alternative approaches. The present study examines if AMPK
      negatively regulates ALK1-mediated signaling events and associated angiogenesis.
      Thus, we treated human umbilical vein endothelial cells with metformin as well as
      other pharmacological AMPK activators and showed that activation of AMPK
      inhibited Smad1/5 phosphorylation and tube formation induced by BMP9. This event
      was mimicked by expression of the active mutant of AMPKalpha1 and prevented by
      the dominant negative AMPKalpha1. Metformin inhibition of BMP9 signaling is
      possibly mediated by upregulation of Smurf1, leading to degradation of ALK1.
      Furthermore, metformin suppressed BMP9-induced angiogenesis in mouse matrigel
      plug. In addition, laser photocoagulation was employed to evaluate the effect of
      metformin. The data revealed that metformin significantly reduced choroidal
      neovascularization to a level comparable to LDN212854, an ALK1 specific
      inhibitor. In conjunction, metformin diminished expression of ALK1 in endothelium
      of the lesion area. Collectively, our study for the first time demonstrates that
      AMPK inhibits ALK1 and associated angiogenesis/neovascularization. This may offer
      us a new avenue for the treatment of related diseases using clinically used
      pharmacological AMPK activators like metformin in combination with other
      strategies to enhance the treatment efficacy or in the case of anti-VEGF
      resistance.

PMID- 28427182
TI  - Identification of DBCCR1 as a suppressor in the development of lung cancer that
      is associated with increased DNA methyltransferase 1.
AB  - Accumulating evidence has pointed to a role of the CpG island hypermethylation in
      the regulation of cancer-related genes in tumor progression. However, the
      biological impacts in cancer pathogenesis associated with down-regulation of such
      gene targets remains elusive. Here we focused on a potential target of
      hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene
      encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is
      significantly lower in the lung cancer tissues compared with adjacent non-tumor
      tissues of patients. Importantly, the decreased DBCCR1 was found correlated with
      more advanced stages of cancer, and with a significantly shorter survival of
      patients. Genetic silencing DBCCR1 in human lung cancer cell line A549 resulted
      in an enhanced proliferation, migration, and invasion capacity. Conversely,
      restoring DBCCR1 expression blocked the growth and inhibited the ability of
      cancer cell in migration and invasion. Interestingly, DBCCR1 attenuates the
      expression of DNMT1 (DNA methyltransferase 1), suggesting a reciprocal regulation
      between genetic silencing of cancer suppressor genes and activating DNA
      methylation. Our data thus implicates DBCCR1 downregulation as a potential module
      in the pathogenesis of lung cancer through DNA methylation.

PMID- 28427184
TI  - KPNB1-mediated nuclear import is required for motility and inflammatory
      transcription factor activity in cervical cancer cells.
AB  - Karyopherin beta1 is a nuclear import protein involved in the transport of
      proteins containing a nuclear localisation sequence. Elevated Karyopherin beta1
      expression has been reported in cancer and transformed cells and is essential for
      cancer cell proliferation and survival. Transcription factors such as NFA B and
      AP-1 contain a nuclear localisation sequence and initiate the expression of
      multiple factors associated with inflammation and cancer cell biology. Our study
      investigated the effect of inhibiting nuclear import via Karyopherin beta1 on
      cancer cell motility and inflammatory signaling using siRNA and the novel small
      molecule, Inhibitor of Nuclear Import-43, INI-43. Inhibition of Karyopherin beta1
      led to reduced migration and invasion of cervical cancer cells. Karyopherin beta1
      is essential for the translocation of NFA B into the nucleus as nuclear import
      inhibition caused its cytoplasmic retention and decreased transcriptional
      activity. A similar decrease was seen in AP-1 transcriptional activity upon
      Karyopherin beta1 inhibition. Consequently reduced interleukin-6, interleukin-1
      beta, tumour necrosis factor alpha and granulocyte macrophage colony stimulating
      factor expression, target genes of NFkB and AP-1, was observed. Migration studies
      inhibiting individual transcription factors suggested that INI-43 may affect a
      combination of signaling events. Our study provides further evidence that
      inhibiting KPNB1 has anti-cancer effects and shows promise as a chemotherapeutic
      target.

PMID- 28427185
TI  - Transcriptional landscape of human cancers.
AB  - The homogeneity and heterogeneity in somatic mutations, copy number alterations
      and methylation across different cancer types have been extensively explored.
      However, the related exploration based on transcriptome data is lacking. In this
      study we explored gene expression profiles across 33 human cancer types using The
      Cancer Genome Atlas (TCGA) data. We identified consistently upregulated genes
      (such as E2F1, EZH2, FOXM1, MYBL2, PLK1, TTK, AURKA/B and BUB1) and consistently
      downregulated genes (such as SCARA5, MYOM1, NKAPL, PEG3, USP2, SLC5A7 and
      HMGCLL1) across various cancers. The dysregulation of these genes is likely to be
      associated with poor clinical outcomes in cancer. The dysregulated pathways
      commonly in cancers include cell cycle, DNA replication, repair, and
      recombination, Notch signaling, p53 signaling, Wnt signaling, TGFbeta signaling,
      immune response etc. We also identified genes consistently upregulated or
      downregulated in highly-advanced cancers compared to lowly-advanced cancers. The
      highly (low) expressed genes in highly-advanced cancers are likely to have higher
      (lower) expression levels in cancers than in normal tissue, indicating that
      common gene expression perturbations drive cancer initiation and cancer
      progression. In addition, we identified a substantial number of genes exclusively
      dysregulated in a single cancer type or inconsistently dysregulated in different
      cancer types, demonstrating the intertumor heterogeneity. More importantly, we
      found a number of genes commonly dysregulated in various cancers such as PLP1,
      MYOM1, NKAPL and USP2 which were investigated in few cancer related studies, and
      thus represent our novel findings. Our study provides comprehensive portraits of
      transcriptional landscape of human cancers.

PMID- 28427186
TI  - MicroRNA-494 promotes apoptosis and extracellular matrix degradation in
      degenerative human nucleus pulposus cells.
AB  - PURPOSE: This study investigated the expression and function of the microRNA-494
      in intervertebral disc degeneration (IDD). RESULTS: MicroRNA-494 expression was
      upregulated during IDD progression; its overexpression increased the expression
      of ECM catabolic factors such as matrix metalloproteinase and A disintegrin and
      metalloproteinase with thrombospondin motif in NP cells while decreasing that of
      anabolic genes such as type II collagen and aggrecan; it also induced the
      apoptosis of NP cells, as determined by flow cytometry. These effects were
      reversed by microRNA-494 inhibitor treatment. SOX9 was identified as a target of
      negative regulation by microRNA-494. Promoter hypomethylation and NF-kappaB
      activation were associated with microRNA-494 upregulation in IDD. MATERIALS AND
      METHODS: MicroRNA-494 expression in degenerative nucleus pulposus (NP) tissue was
      assessed by quantitative real-time PCR. The effect of microRNA-494 on
      extracellular matrix (ECM) metabolism and NP cell apoptosis was evaluated by
      transfection of microRNA-494 mimic or inhibitor. The regulation of SRY-related
      high mobility group box (SOX)9 expression by microRNA-494 was assessed with the
      luciferase reporter assay, and the methylation status of the microRNA-494
      promoter was evaluated by methylation-specific PCR and bisulfite sequencing PCR.
      The role of activated nuclear factor (NF)-kappaB in the regulation of microRNA
      494 expression was evaluated using specific inhibitors. CONCLUSIONS: MicroRNA-494
      promotes ECM degradation and apoptosis of degenerative human NP cells by directly
      targeting SOX9.

PMID- 28427187
TI  - RITA displays anti-tumor activity in medulloblastomas independent of TP53 status.
AB  - Current therapy of medulloblastoma, the most common malignant brain tumor of
      childhood, achieves 40-70% survival. Secondary chemotherapy resistance
      contributes to treatment failure, where TP53 pathway dysfunction plays a key
      role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53
      functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2
      binding may have therapeutic potential. We show here that RITA decreased
      viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53
      functional status. The decrease in cell viability was accompanied in 3 of the 4
      medulloblastoma cell lines by accumulation of TP53 protein in the cells and
      increased CDKN1A expression. RITA treatment in mouse models inhibited
      medulloblastoma xenograft tumor growth. These data demonstrate that RITA
      treatment reduces medulloblastoma cell viability in both in vitro and in vivo
      models, and acts independently of cellular TP53 status, identifying RITA as a
      potential therapeutic agent to treat medulloblastoma.

PMID- 28427188
TI  - Consumption of fruits and vegetables and risk of renal cell carcinoma: a meta
      analysis of observational studies.
AB  - BACKGROUND: There have been inconsistent results about the association between
      consumption of fruits and vegetables and renal cell carcinoma (RCC) risk. We
      conducted a meta-analysis of the published observational studies to explore this
      association. RESULTS: Nineteen observational studies (4 cohort, 1 pooled and 14
      case-control studies), involving 10,215 subjects with RCC were part of this meta
      analysis. The SRR for the highest vs. the lowest intake of vegetables was 0.73
      (95% CI: 0.63-0.85; Pheterogeneity = 0.004, I2 = 53.5%), whereas for fruits it
      was 0.86 (95% CI: 0.75-0.98; Pheterogeneity = 0.012, I2 = 47.4%). Linear dose
      response analysis also showed similar results, e.g., for per 1 serving/day
      increment of vegetables, the SRR was 0.90 (95% CI: 0.84-0.96) and for fruits it
      was 0.97 (95% CI: 0.93-1.01). Nonlinear association was only observed for
      vegetables (Pnonlinearity = 0.001), but not for fruits (Pnonlinearity = 0.221).
      MATERIALS AND METHODS: Eligible studies up to August 31, 2016 were identified and
      retrieved by searching MEDLINE and EMBASE databases along with manual review of
      the reference list from the retrieved studies. Quality of included studies was
      evaluated using Newcastle-Ottawa Quality Assessment Scale (NOS). Random-effects
      model was used to calculate summary relative risk (SRR) and corresponding 95%
      confidence interval (CI). CONCLUSIONS: This meta-analysis indicated a protective
      effect of consumption of vegetables and fruits on RCC risk. Further studies are
      warranted with prospective designs that use validated questionnaires and control
      for important confounders.

PMID- 28427189
TI  - Identifying biomarkers of papillary renal cell carcinoma associated with
      pathological stage by weighted gene co-expression network analysis.
AB  - Although papillary renal cell carcinoma (PRCC) accounts for 10%-15% of renal cell
      carcinoma (RCC), no predictive molecular biomarker is currently applicable to
      guiding disease stage of PRCC patients. The mRNASeq data of PRCC and adjacent
      normal tissue in The Cancer Genome Atlas was analyzed to identify 1148
      differentially expressed genes, on which weighted gene co-expression network
      analysis was performed. Then 11 co-expressed gene modules were identified. The
      highest association was found between blue module and pathological stage (r =
      0.45) by Pearson's correlation analysis. Functional enrichment analysis revealed
      that biological processes of blue module focused on nuclear division, cell cycle
      phase, and spindle (all P < 1e-10). All 40 hub genes in blue module can
      distinguish localized (pathological stage I, II) from non-localized (pathological
      stage III, IV) PRCC (P < 0.01). A good molecular biomarker for pathological stage
      of RCC must be a prognostic gene in clinical practice. Survival analysis was
      performed to reversely validate if hub genes were associated with pathological
      stage. Survival analysis unveiled that all hub genes were associated with patient
      prognosis (P < 0.01).The validation cohort GSE2748 verified that 30 hub genes can
      differentiate localized from non-localized PRCC (P < 0.01), and 18 hub genes are
      prognosis-associated (P < 0.01).ROC curve indicated that the 17 hub genes
      exhibited excellent diagnostic efficiency for localized and non-localized PRCC
      (AUC > 0.7). These hub genes may serve as a biomarker and help to distinguish
      different pathological stages for PRCC patients.

PMID- 28427190
TI  - Pygopus2 inhibits the efficacy of paclitaxel-induced apoptosis and induces
      multidrug resistance in human glioma cells.
AB  - Anti-microtubule drugs, such as paclitaxel (PTX), are extensively used for the
      treatment of numerous cancers. However, growing evidence has shown that PTX
      resistance, either intrinsic or acquired, frequently occurs in patients and
      results in the failure of treatment, contributing to the high cancer mortality
      rate. Therefore, it is necessary to identify the genes or pathways involved in
      anti-microtubule drug resistance for future successful treatment of cancers.
      Pygopus2 (Pygo2), which contains a Zn-coordinated plant homeodomain (PHD) finger
      domain, is critical for beta-catenin-dependent transcriptional switches in normal
      and malignant tissues and is over-expressed in various cancers, including human
      brain glioma. In this study, we report that over-expression of Pygo2 inhibited
      the efficacy of PTX and contributed to cell multidrug resistance in two different
      ways. First, over-expression of Pygo2 inhibited the PTX-induced phosphorylation
      of B-cell lymphoma 2 (Bcl-2), suppressing the proteolytic cleavage of procaspase
      8/9 and further inhibiting the activation of caspase-3, which also inhibits the
      activation of the JNK/SAPK pathway, ultimately inhibiting cell apoptosis. Second,
      over-expression of Pygo2 facilitated the expression of P-glycoprotein, which acts
      as a drug efflux pump, by promoting the transcription of Multi-drug resistance 1
      (MDR1) at the MDR1 promoter loci, resulting in acceleration of the efflux of PTX.

PMID- 28427191
TI  - Down-regulation of long non-coding RNA RP11-708H21.4 is associated with poor
      prognosis for colorectal cancer and promotes tumorigenesis through regulating
      AKT/mTOR pathway.
AB  - Long non-coding RNAs (lncRNAs) serve critical roles in cancer development and
      progression. Herein, through next generation RNA sequencing and experimental
      validations, we determined the expression status of RP11-708H21.4 in colorectal
      cancer (CRC) and explored its clinical significance and biological functions in
      CRC. Differentially expressed lncRNAs from CRC samples and corresponding normal
      mucosa tissues was screened through RNA sequencing, and RP11-708H21.4 was
      selected for further experimental validation. The expression levels of RP11
      708H21.4 in CRC tissues and cell lines were determined using qRT-PCR. Also, the
      relationship between the clinicopathological features and RP11-708H21.4
      expression was analyzed. Cell viability was examined by CCK-8 and colony assays;
      cell migration and invasion were detected by transwell assays; cell cycle and
      cell apoptosis were analyzed by flow cytometry. The chemosensitivity of CRC cells
      to 5-Fluorouracil (5-FU) was also determined using CCK-8 assay. CRC xenograft
      tumor models were established to determine the biological functions of RP11
      708H21.4 in vivo. Levels of cell cycle-related proteins and AKT/mTOR pathway
      related proteins were detected by western blot assay. RP11-708H21.4 expression
      was aberrantly decreased in CRC, and its expression was closely associated with
      aggressive clinicopathologic features and unfavorable prognosis of CRC patients.
      Overexpressed RP11-708H21.4 suppresses CRC cell proliferation through inducing G1
      arrest. Moreover, up-regulation of RP11-708H21.4 inhibits cell migration and
      invasion, causes cell apoptosis, and enhances 5-FU sensitivity of CRC cells.
      Finally, increased RP11-708H21.4 expression blocked AKT/mTOR pathway, and
      repressed in vivo CRC xenograft tumor growth. The results indicated that RP11
      708H21.4 might have potential roles as a biomarker and a therapeutic target for
      CRC.

PMID- 28427192
TI  - DNA methylation directly downregulates human cathelicidin antimicrobial peptide
      gene (CAMP) promoter activity.
AB  - LL-37, the active product of human cathelicidin antimicrobial peptide (CAMP) has
      a broad spectrum of antibacterial activity. LL-37 also has important
      physiological functions in immune regulation, angiogenesis and in modulating
      apoptosis. The roles of LL-37 in oral squamous cell carcinoma (OSCC) are still
      not clear. The correlation between DNA methylation and human CAMP expression is
      also unknown. Here human CAMP/LL-37 expression was assessed by
      immunohistochemistry in normal and OSCC tissues. The results indicated that low
      expression of CAMP/LL-37 correlated with histological differentiation and lymph
      node metastasis and also promoted tumor progression. A cell-specific methylation
      pattern in the promoter region of human CAMP was detected. Treatment with 5-aza
      2'-deoxycytidine, a DNA demethylation reagent can increase human CAMP expression
      in epithelial cancer cells. The reporter assay showed that unmethylated human
      CAMP promoter activity was significantly higher than methylated promoter
      activity. Taken together, these results suggested that human CAMP/LL-37 might act
      as a tumor-suppressor in OSCC and DNA methylation might play roles during
      carcinogenesis via directly downregulating human CAMP promoter activity.

PMID- 28427193
TI  - Targeting high Aurora kinases expression as an innovative therapy for
      hepatocellular carcinoma.
AB  - The Aurora kinases A and B control tumorigenesis by inhibiting apoptosis and
      promoting proliferation and metastasis, however, it remains unknown whether
      Aurora A and B overexpressed concomitantly and its clinical significance in
      hepatocellular carcinoma (HCC). Here, we obsearved Aurora A and B tended to
      overexpress parallelly on protein level (r = 0.8679, P < 0.0001) and their co
      overexpression (Aurora AHBH), associated with the worst prognosis, was an
      independent predictor for the survival. Importantly, with the lower IC50 and
      stronger anti-tumor effect than selective inhibitors, SNS-314, the pan-inhibitor
      of Aurora kinases, which induced YAP (Yes-associated protein) reduction and
      resulted in P21 accumulation, significantly promoted the polyploidy (> 4N)
      formation and apoptosis in HCC. High YAP expression (YAPH) was associated with
      Aurora AHBH, and appeared to be an independent predictor for survival, but P21
      not. Moreover, silencing YAP also induced P21 accumulation, and knockdown P21,
      which enhanced YAP accumulation and weakened the SNS-314-induced YAP reduction,
      impaired SNS-314-induced apoptosis. Therefore, P21 enhanced the apoptotic effect
      of SNS-314 in HCC. Taken together, our findings indicated Aurora kinases/YAP/P21
      was an oncogenic signaling axis in HCC, and revealed targeting Aurora AHBH
      induced apoptosis by YAP suppression. Our results also provided a solid evidence
      for SNS-314 as a potential targeted therapy, and a proof-of-concept evidence for
      a possible combined therapy of SNS-314 plus Hippo pathway inhibitors on HCC.

PMID- 28427194
TI  - Alternative RNA splicing of the MEAF6 gene facilitates neuroendocrine prostate
      cancer progression.
AB  - Although potent androgen receptor pathway inhibitors (ARPI) improve overall
      survival of metastatic prostate cancer patients, treatment-induced neuroendocrine
      prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is
      becoming a more common clinical issue. Improved understanding of the molecular
      biology of t-NEPC is essential for the development of new effective management
      approaches for t-NEPC. In this study, we identify a splice variant of the
      MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in
      both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung
      cancers. We show that MEAF6-1 splicing is stimulated by neuronal RNA splicing
      factor SRRM4. Rather than inducing neuroendocrine trans-differentiation of cells
      in prostate adenocarcinoma, MEAF6-1 upregulation stimulates cell proliferation,
      anchorage-independent cell growth, invasion and xenograft tumor growth. Gene
      microarray identifies that these MEAF6-1 actions are in part mediated by the ID1
      and ID3 genes. These findings suggest that the MEAF6-1 variant does not induce
      neuroendocrine differentiation of prostate cancer cells, but rather facilitates t
      NEPC progression by increasing the proliferation rate of cells that have acquired
      neuroendocrine phenotypes.

PMID- 28427195
TI  - Screening effective differential expression genes for hepatic carcinoma with
      metastasis in the peripheral blood mononuclear cells by RNA-seq.
AB  - Tumor metastasis is a multistep process involving a number of genetic alterations
      so that the genetic diagnosis is got increasingly attentions today. The aim of
      this study was to use RNA-seq to screen the effective differential expression
      genes in the peripheral blood mononuclear cells for the hepatic carcinoma with
      metastasis. The results showed that hepatic carcinoma samples gathered according
      to different metastasis. CCL3, CCL3L1, JUN, IL8, and IL1B were identified in
      inflammation mediated by chemokine and cytokine signaling pathway (P00031) in the
      hepatic carcinoma samples with metastasis, and subsequently confirmed by
      quantitative real-time polymerase chain reaction. In conclusions, CCL3, CCL3L1,
      JUN, IL8, and IL1B have the potential to be considered as candidates for future
      molecular diagnosis of the hepatic carcinoma with metastasis. This work may
      provide us with new visions into the metastasis process and potential efficient
      clinical diagnosis in the future.

PMID- 28427196
TI  - Breast cancer subtypes predict the preferential site of distant metastases: a
      SEER based study.
AB  - BACKGROUND AND AIMS: This study aimed to access possible relationships between
      breast cancer subtypes and sites of distant metastasis in breast cancer. RESULTS:
      A total of 243,896 patients, including 226,451 cases in control groups were
      identified. Bone metastasis was found in 8848 cases, compared with 1,000 brain
      metastasis cases, 3434 liver metastasis cases and 4167 lung metastasis cases.
      Patients with all subtypes were most prone to bone metastases, the incidence of
      bone metastasis in HR+/HER2+ subtype was up to 5.1 %. Further, HR-/HER2+ subtype
      patients had a higher probability of brain (OR = 1.978) metastasis compared to
      HR+/HER2- subtype patients. In addition, liver metastasis was more frequently
      observed in the HER2 positive subtypes compared with HER2 negative subtypes.
      Patients with TN primarily presented lung metastasis, but it made no difference
      in the probability of lung metastases of all subtypes. MATERIALS AND METHODS:
      Using the 2010-2013 Surveillance, Epidemiology, and End Results Program(SEER)
      data, a retrospective, population-based cohort study to investigate tumor
      subtypes-specific differences in the sites of distant metastasis. Metastatic
      patterns information was provided for bone, brain, liver and lung. The breast
      cancer was classified into four subtypes: hormone receptor (HR) +/ human
      epidermal growth factor receptor 2 (HER2) -, HR+/HER2+, HR-/HER2+ and triple
      negative (TN). CONCLUSIONS: The pathological subtypes of breast cancer are
      clearly different in metastatic behavior with regard to the sites of distant
      metastasis, emphasizing that this knowledge may help to determine the appropriate
      strategy for follow-up and guide personalized medicine.

PMID- 28427197
TI  - ROR1 expression as a biomarker for predicting prognosis in patients with
      colorectal cancer.
AB  - There is a lack of reliable prognosis biomarker in the current treatment of
      colorectal cancer. The receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is
      overexpressed and associated with poor prognosis in certain tumors. This study
      aimed to explore the prognostic significance of ROR1 in colorectal cancer.
      Western blot analysis and immunohistochemistry showed that the expression of ROR1
      in colorectal cancer was significantly higher than that in the adjacent normal
      tissues. ROR1 expression was positively associated with the clinical stage and
      lymph-node metastasis (p < 0.01). Kaplan-Meier survival analysis revealed that
      patients with higher ROR1 expression had a significantly shorter overall survival
      (p < 0.01). Multivariate Cox regression analysis confirmed that ROR1 is an
      independent prognostic marker in colorectal cancer (p = 0.002, HR = 2.08, 95% CI:
      1.314-3.292). Thus, our study demonstrated that ROR1 expression is correlated
      with malignant attributes and may serve as a novel prognostic marker and
      therapeutic target for colorectal cancer.

PMID- 28427198
TI  - Hypoxia activates placental growth factor expression in lymphatic endothelial
      cells.
AB  - Placental growth factor (PlGF), a proangiogenic member of vascular endothelial
      growth family, is active during pathological conditions like cancer, metastasis
      formation and hind limb ischemia and in wound healing. Endothelial cells express
      PlGF and hypoxia positively modulates in vitro its expression. To verify whether
      hypoxia modulates PlGF expression in different cellular contexts and in vivo, we
      first analyzed five human and five mouse cancer cell lines showing that in eight
      of them hypoxia positively modulates PlGF. Next, we analyzed xenograft colorectal
      cancer tumors showing that human cancer cells were able to express PlGF in
      hypoxic area of the tumor. Surprisingly, we did not visualize mouse PlGF in CD31
      positive tumor vessels, but in low CD31 positive vessels, a characteristic of
      lymphatic vessels. We found that hypoxia effectively activates PlGF expression in
      lymphatic endothelial cells as well as in LYVE1 positive tumor vessels. We also
      investigated two additional mouse angiogenic models, hind limb ischemia and wound
      healing, and we confirmed that lymphatic vessels of both ischemic muscles and
      skin express PlGF. These results show for the first time that hypoxia activates
      PlGF expression in lymphatic endothelial cells, which have to be considered an
      additional source for PlGF production in pathological contexts.

PMID- 28427199
TI  - Combinatorial treatment with polyI:C and anti-IL6 enhances apoptosis and
      suppresses metastasis of lung cancer cells.
AB  - Activation of TLR3 stimulates cancer cell apoptosis and triggers secretion of
      inflammatory cytokines. PolyI:C, a TLR3 agonist, activates immune cells and
      regresses metastatic lung cancer in vivo. Although polyI:C reportedly kills lung
      carcinomas, the mechanism remains elusive. Here, we demonstrated that polyI:C
      suppressed the proliferation and survival of metastatic (NCI-H358 and NCI-H292)
      and non-metastatic (A549) lung cancer cells. Notably, A549, NCI-H292 and NCI-H358
      which are inducible by polyI:C, expressed low-to-medium level of TLR3 protein,
      and were susceptible to polyI:C treatment. By contrast, NCI-H1299, which
      endogenously expresses high level of TLR3 protein, was insensitive to polyI:C. We
      showed that polyI:C stimulated pro-inflammatory cytokines associated with
      survival and metastasis in a cell type-specific manner. While A549 and NCI-H292
      released high levels of IL6, IL8 and GRO, the NCI-H358 cells endogenously
      secretes abundant levels of these cytokines, and was not further induced by
      polyI:C. Thus, NCI-H358 was resistant to the inhibition of cytokine-dependent
      metastasis. NCI-H1299, which was unresponsive to polyI:C, did not produce any of
      the pro-inflammatory cytokines. Treatment of A549 with a combination of polyI:C
      and anti-IL6 antibody significantly decreased IL6 production, and enhanced
      polyI:C-mediated killing and suppression of oncogenicity and metastasis. While
      polyI:C stimulated the phosphorylation of STAT3 and JAK2, blockade of these
      proteins enhanced polyI:C-mediated suppression of survival and metastasis. Taken
      together, polyI:C alone provoked apoptosis of lung cancer cells that express low
      to-medium levels of functional TLR3 protein. The combinatorial treatment with
      polyI:C and anti-IL6 enhanced polyI:C-mediated anticancer activities through
      IL6/JAK2/STAT3 signalling, and apoptosis via TLR3-mediated caspase 3/8 pathway.

PMID- 28427201
TI  - Wnt5a / planar cell polarity signaling pathway in urothelial carcinoma, a
      potential prognostic biomarker.
AB  - Bladder cancer is the fourth most common cancer in men and the most common
      malignancy of the urinary tract. Bladder cancers detected at an early stage have
      a very high five-year survival rate, but when detected after local metastasis the
      rate is only about 50%. Our group recently reported a positive correlation
      between the expression of Wnt5a, a member of the Wnt proteins family, and
      histopathological grade and stage of urothelial carcinoma (UC). The objective of
      this study was to analyze UC cases reported in Athens, Ohio and investigate the
      major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC
      human tissue samples and UC cell lines.Formalin fixed and paraffin embedded
      transurethral resection tissues were immunostained for Wnt5a, Ror-2, CTHRC1 and E
      cadherin. In addition, in vitro studies using UC cell lines were investigated for
      Wnt5a/PCP signaling and epithelial mesenchymal transition (EMT) gene expression.
      The IHC results showed a correlation between the expression of Wnt5a, Ror2 and
      CTHRC1 with high histological grade of the tumor, while E-cadherin showed an
      opposite trend of expression. Real time RT-PCR results showed that RNA expression
      of the Wnt5a/ PCP pathway genes vary in low and high grade UC cell lines and that
      the high grade cell lines exhibited signs of EMT.These findings support that
      Wnt5a-Ror2 signaling plays a role in UC, support the potential use of Wnt5a as a
      prognostic marker and provide evidence that Wnt5a signaling may be used as an
      effective molecular target for novel therapeutic tools.

PMID- 28427200
TI  - IDH1 R132H mutation regulates glioma chemosensitivity through Nrf2 pathway.
AB  - PURPOSE: Numerous studies have reported that glioma patients with isocitrate
      dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment.
      However, the mechanism of IDH1 mutations on the chemosensitivity of glioma
      remains unclear. In this study, we investigated the role and the potential
      mechanism of Nrf2 in IDH1 R132H-mediated drug resistance. METHODS: Wild type IDH1
      (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells
      and U251 cells overexpressing IDH1 were generated. Phenotypic differences between
      IDH1-WT and IDH1 R132H overexpressing cells were evaluated using MTT, cell colony
      formation assay, scratch test assay and flow cytometry. Expression of IDH1 and
      its associated targets, nuclear factor-erythroid 2-related factor 2 (Nrf2),
      NAD(P)H quinine oxidoreductase 1 (NQO1), multidrug resistant protein 1 (MRP1) and
      p53 were analyzed. RESULTS: The IDH1 R132H overexpressing cells were more
      sensitive to temozolomide than WT and the control, and Nrf2 was significantly
      decreased in IDH1 R132H overexpressing cells. We found that knocking down Nrf2
      could decrease resistance to temozolomide. The nuclear translocation of Nrf2 in
      IDH1 R132H overexpressing cells was lower than the WT and the control groups
      after temozolomide treatment. When compared with WT cells, NQO1 expression was
      reduced in IDH1 R132H cells, especially after temozolomide treatment. P53 was
      involved in the resistance mechanism of temozolomide mediated by Nrf2 and NQO1.
      CONCLUSIONS: Nrf2 played an important role in IDH1 R132H-mediated drug
      resistance. The present study provides new insight for glioma chemotherapy with
      temozolomide.

PMID- 28427202
TI  - Clinical implications of genomic profiles in metastatic breast cancer with a
      focus on TP53 and PIK3CA, the most frequently mutated genes.
AB  - Breast cancer (BC) has been genetically profiled through large-scale genome
      analyses. However, the role and clinical implications of genetic alterations in
      metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome
      sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of
      another 29 MBCs. We evaluated somatic mutations from WES and targeted sequencing
      and assessed gene expression and performed pathway analysis from RNA-Seq. In this
      analysis, PIK3CA was the most commonly mutated gene in estrogen receptor (ER)
      positive BC, while in ER-negative BC, TP53 was the most commonly mutated gene (p
      = 0.018 and p < 0.001, respectively). TP53 stopgain/loss and frameshift mutation
      was related to low expression of TP53 in contrast nonsynonymous mutation was
      related to high expression. The impact of TP53 mutation on clinical outcome
      varied with regard to ER status. In ER-positive BCs, wild type TP53 had a better
      prognosis than mutated TP53 (median overall survival (OS) (wild type vs.
      mutated): 88.5 +/- 54.4 vs. 32.6 +/- 10.7 (months), p = 0.002). In contrast,
      mutated TP53 had a protective effect in ER-negative BCs (median OS: 0.10 vs. 32.6
      +/- 8.2, p = 0.026). However, PIK3CA mutation did not affect patient survival. In
      gene expression analysis, CALM1, a potential regulator of AKT, was highly
      expressed in PIK3CA-mutated BCs. In conclusion, mutation of TP53 was associated
      with expression status and affect clinical outcome according to ER status in MBC.
      Although mutation of PIK3CA was not related to survival in this study, mutation
      of PIK3CA altered the expression of other genes and pathways including CALM1 and
      may be a potential predictive marker of PI3K inhibitor effectiveness.

PMID- 28427203
TI  - Regional structural impairments outside lesions are associated with verbal short
      term memory deficits in chronic subcortical stroke.
AB  - BACKGROUND AND PURPOSE: We aimed to explore the neural mechanisms of verbal short
      term memory (VSTM) impairment in subcortical stroke by evaluating the
      contributions of lesion and remote grey matter volume (GMV) reduction. RESULTS:
      There was no significant correlation between lesions and VSTM. In stroke patients
      with left lesions, GMV reductions in the right middle frontal gyrus and in the
      left inferior frontal gyrus were positively correlated with VSTM impairment. In
      patients with right lesions, GMV reduction in the right dorsal posterior
      cingulate cortex was positively correlated with VSTM impairment. MATERIALS AND
      METHODS: Ninety-seven patients with chronic subcortical ischemic stroke and
      seventy-nine healthy controls underwent VSTM and structural MRI examinations.
      Voxel-based lesion symptom mapping was used to identify correlations between
      lesions and VSTM. Voxel-wise comparisons were used to identify brain regions with
      significant GMV reduction in patients with left and right lesions. These regions
      were used in correlation analyses between GMV and VSTM in each patient subgroup.
      CONCLUSIONS: These findings suggest that VSTM impairment in subcortical stroke is
      associated with secondary regional structural damage in non-lesion regions,
      rather than with the lesion itself. Moreover, different neural substrates may
      underlie VSTM impairment in stroke patients with left and right lesions.

PMID- 28427205
TI  - MNS16A tandem repeat minisatellite of human telomerase gene: functional studies
      in colorectal, lung and prostate cancer.
AB  - MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the
      promoter region of an antisense transcript of the human telomerase reverse
      transcriptase gene. MNS16A promoter activity depends on the variable number of
      tandem repeats (VNTR) presenting varying numbers of transcription factor binding
      sites for GATA binding protein 1. Although MNS16A has been investigated in
      multiple cancer epidemiology studies with incongruent findings, functional data
      of only two VNTRs (VNTR-243 and VNTR-302) were available thus far, linking the
      shorter VNTR to higher promoter activity.For the first time, we investigated
      promoter activity of all six VNTRs of MNS16A in cell lines of colorectal, lung
      and prostate cancer using Luciferase reporter assay. In all investigated cell
      lines shorter VNTRs showed higher promoter activity. While this anticipated
      indirect linear relationship was affirmed for colorectal cancer SW480 (P =
      0.006), a piecewise linear regression model provided significantly better model
      fit in lung cancer A-427 (P = 6.9 * 10-9) and prostate cancer LNCaP (P = 0.039).
      In silico search for transcription factor binding sites in MNS16A core repeat
      element suggested a higher degree of complexity involving X-box binding protein
      1, general transcription factor II-I, and glucocorticoid receptor alpha in
      addition to GATA binding protein 1.Further functional studies in additional
      cancers are requested to extend our knowledge of MNS16A functionality uncovering
      potential cancer type-specific differences. Risk alleles may vary in different
      malignancies and their determination in vitro could be relevant for
      interpretation of genotype data.

PMID- 28427204
TI  - An extensive molecular cytogenetic characterization in high-risk chronic
      lymphocytic leukemia identifies karyotype aberrations and TP53 disruption as
      predictors of outcome and chemorefractoriness.
AB  - We investigated whether karyotype analysis and mutational screening by next
      generation sequencing could predict outcome in 101 newly diagnosed chronic
      lymphocytic leukemia patients with high-risk features, as defined by the presence
      of unmutated IGHV gene and/or 11q22/17p13 deletion by FISH and/or TP53 mutations.
      Cytogenetic analysis showed favorable findings (normal karyotype and isolated
      13q14 deletion) in 30 patients, unfavorable (complex karyotype and/or 17p13/11q22
      deletion) in 34 cases and intermediate (all other abnormalities) in 36 cases. A
      complex karyotype was present in 21 patients. Mutations were detected in 56 cases
      and were associated with unmutated IGHV status (p = 0.040) and complex karyotype
      (p = 0.047). TP53 disruption (i.e. TP53 mutations and/or 17p13 deletion by FISH)
      correlated with the presence of >= 2 mutations (p = 0.001) and a complex
      karyotype (p = 0.012). By multivariate analysis, an advanced Binet stage (p <
      0.001) and an unfavorable karyotype (p = 0.001) predicted a shorter time to first
      treatment. TP53 disruption (p = 0.019) and the unfavorable karyotype (p = 0.028)
      predicted a worse overall survival. A shorter time to chemorefractoriness was
      associated with TP53 disruption (p = 0.001) and unfavorable karyotype (p =
      0.025). Patients with both unfavorable karyotype and TP53 disruption presented a
      dismal outcome (median overall survival and time to chemorefractoriness of 28.7
      and 15.0 months, respectively). In conclusion, karyotype analysis refines risk
      stratification in high-risk CLL patients and could identify a subset of patients
      with highly unfavorable outcome requiring alternative treatments.

PMID- 28427206
TI  - miR-146a and miR-146b promote proliferation, migration and invasion of follicular
      thyroid carcinoma via inhibition of ST8SIA4.
AB  - Follicular thyroid carcinoma (FTC) is a more aggressive form of thyroid cancer
      than the common papillary type. Alpha-2,8-sialyltransferase (ST8SIA) family
      members are expressed in various cancers and may be associated with FTC
      progression. In this study, we measured ST8SIA family expression in two FTC cell
      lines with different invasive potentials (FTC-133 and FTC-238) and Nthy-ori 3-1
      cell lines, as well as FTC and normal thyroid tissues. ST8SIA4 was downregulated
      in the highly invasive FTC-238 cells and FTC tissues. Additionally, ST8SIA4
      inhibited proliferation, migration and invasion of FTC both in vitro and in vivo.
      miR-146a and miR-146b were previously shown to be upregulated in thyroid
      carcinoma, and bioinformatics analyses indicated that miR-146a and miR-146b
      inhibit ST8SIA4. We found that miR-146a and miR-146b were significantly
      upregulated in FTC and promoted tumour progression. Furthermore, ST8SIA4
      restoration decreased the invasiveness of miR-146a/b-overexpressing FTC-133
      cells, and ST8SIA4 suppression reversed the effects of miR-146a/b inhibition in
      FTC-238 cells. We showed that miR-146a/b activated the PI3K-AKT-mTOR signalling
      pathway at least partially via suppression of ST8SIA4. Thus, our results
      demonstrate that miR-146a and miR-146b promote proliferation, migration and
      invasion of FTC via inhibition of ST8SIA4.

PMID- 28427207
TI  - miR-205 inhibits cell growth by targeting AKT-mTOR signaling in progesterone
      resistant endometrial cancer Ishikawa cells.
AB  - PURPOSE: miR-205 is significantly up-regulated in endometrioid adenocarcinoma. In
      this study, the significant anticancer effect of a miR-205 inhibitor was
      investigated in both endometrial carcinoma and progesterone-resistant endometrial
      carcinoma cells. RESULTS: Compared with Ishikawa endometrial cancer cells, miR
      205 was expressed at higher levels in a progesterone-resistant (PR) sub-cell
      line. Inhibition of miR-205 suppressed the growth of cancer cells in a dose- and
      time-dependent manner. Moreover, the miR-205 inhibitor induced a marked increase
      in the percentage of Ishikawa-PR cells in G2/M phases and a decrease in the
      percentage of cells in G0/G1 and S phases. In addition, miR-205 inhibitor-treated
      tumor cells exhibited increased apoptosis. Moreover, miR-205 was found to
      negatively regulate PTEN expression and lead to autophagy and activation of the
      AKT/mTOR pathway in PR cells, and PTEN protein levels significantly decreased
      with development of progesterone resistance in endometrial cancer cells. Western
      blot assay showed up-regulated autophagy, as indicated by expression of LC3
      II/LC3-I and beclin1, in Ishikawa cells; in particular, autophagy was markedly
      induced in PR cells treated with the miR-205 inhibitor. MATERIALS AND METHODS: We
      measured and analyzed cell growth curves with and without miR-205 inhibition with
      the MTT assay, miR-205 expression by qRT-PCR, cell cycle and apoptosis using
      annexin V/propidium iodide staining and flow cytometry, and autophagy, apoptosis,
      and AKT-mTOR signaling by western blotting. CONCLUSIONS: Inhibition of miR-205,
      which targets the AKT-mTOR pathway, in endometrial cancer cells provides a
      potential, new treatment for PR endometrial carcinoma.

PMID- 28427208
TI  - Identification of differentially expressed lncRNAs involved in transient
      regeneration of the neonatal C57BL/6J mouse heart by next-generation high
      throughput RNA sequencing.
AB  - Previous studies have shown that mammalian cardiac tissue has a regenerative
      capacity. Remarkably, neonatal mice can regenerate their cardiac tissue for up to
      6 days after birth, but this capacity is lost by day 7. In this study, we aimed
      to explore the expression pattern of long noncoding RNA (lncRNA) during this
      period and examine the mechanisms underlying this process. We found that 685
      lncRNAs and 1833 mRNAs were differentially expressed at P1 and P7 by the next
      generation high-throughput RNA sequencing. The coding genes associated with
      differentially expressed lncRNAs were mainly involved in metabolic processes and
      cell proliferation, and also were potentially associated with several key
      regeneration signalling pathways, including PI3K-Akt, MAPK, Hippo and Wnt. In
      addition, we identified some correlated targets of highly-dysregulated lncRNAs
      such as Igfbp3, Trnp1, Itgb6, and Pim3 by the coding-noncoding gene co-expression
      network. These data may offer a reference resource for further investigation
      about the mechanisms by which lncRNAs regulate cardiac regeneration.

PMID- 28427209
TI  - HIF1alpha regulates single differentiated glioma cell dedifferentiation to stem
      like cell phenotypes with high tumorigenic potential under hypoxia.
AB  - The standard treatment for Glioblastoma multiforme (GBM) is surgical resection
      and subsequent radiotherapy and chemotherapy. Surgical resection of GBM is
      typically restricted because of its invasive growth, which results in residual
      tumor cells including glioma stem cells (GSCs) and differentiated cells.
      Recurrence has been previously thought to occur as a result of these GSCs, and
      hypoxic microenvironment maintains the GSCs stemness also plays an important
      role. Summarizing traditional studies and we find many researchers ignored the
      influence of hypoxia on differentiated cells. We hypothesized that the residual
      differentiated cells may be dedifferentiated to GSC-like cells under hypoxia and
      play a crucial role in the rapid, high-frequency recurrence of GBM. Therefore,
      isolated CD133-CD15-NESTIN- cells were prepared as single-cell culture and
      treated with hypoxia. More than 95% of the surviving single differentiated CD133
      CD15-NESTIN- cell dedifferentiated into tumorigenic CD133+CD15+NESTIN+ GSCs, and
      this process was regulated by hypoxia inducible factor-1alpha. Moreover, the
      serum also played an important role in this dedifferentiation. These findings
      challenge the traditional glioma cell heterogeneity model, cell division model
      and glioma malignancy development model. Our study also highlights the mechanism
      of GBM recurrence and the importance of anti-hypoxia therapy. In addition to
      GSCs, residual differentiated tumor cells also substantially contribute to
      treatment resistance and the rapid, high recurrence of GBM.

PMID- 28427210
TI  - Dependence of p53-deficient cells on the DHX9 DExH-box helicase.
AB  - DHX9 is a DExH-box helicase family member with key regulatory roles in a broad
      range of cellular processes. It participates at multiple levels of gene
      regulation, including DNA replication, transcription, translation, RNA transport,
      and microRNA processing. It has been implicated in tumorigenesis and recent
      evidence suggests that it may be a promising chemotherapeutic target. Previous
      studies have determined that DHX9 suppression elicits an apoptotic or senescence
      response by activating p53 signaling. Here, we show that DHX9 inhibition can also
      have deleterious effects in cells lacking functional p53. Loss of DHX9 led to
      increased cell death in p53-deficient mouse lymphomas and HCT116 human colon
      cancer cells, and G0/G1 cell cycle arrest in p53-deficient mouse embryonic
      fibroblasts. Analysis of mRNA levels for p53 transcriptional targets showed that
      a subset of p53 targets in the p53-null lymphomas and HCT116 cells were activated
      despite the absence of functional p53. This implies an alternative pathway of
      DHX9-mediated activation of cell death and cell cycle arrest in p53-deficient
      cells and supports the feasibility of targeting DHX9 in p53-deficient tumors.

PMID- 28427211
TI  - Association of BRM promoter polymorphisms and esophageal adenocarcinoma outcome.
AB  - PURPOSE: Brahma (BRM) is a critical catalytic subunit of the SWI/SNF chromatin
      remodeling complex; expression of BRM is commonly lost in various cancer types.
      BRM promoter polymorphisms (BRM-741; BRM-1321) are associated with loss of BRM
      expression, and with cancer risk/survival. We evaluated these two polymorphisms
      in the overall survival (OS) of esophageal adenocarcinoma (EAC) patients.
      RESULTS: Of 270 patients, 37% were stage IV. Minor allele frequencies were 47
      49%; 15% were double-homozygotes. When compared to the wild-type genotype, the
      homozygous variant of BRM-741 carried an adjusted OS hazard ratio (aHR) of 1.64
      (95% CI:1.1-2.4); for BRM-1321, the aHR was 2.09 (95% CI:1.4-3.0). Compared to
      the double wild-type, carrying homozygous variants of both promoter polymorphisms
      (double-homozygote) yielded an aHR of 2.21 (95% CI:1.4-3.6).
      Directions/magnitudes of associations were similar in subsets by age, gender,
      smoking status, use of platinum agents, and disease stage, and for progression
      free survival. MATERIALS AND METHODS: In a cohort of EAC patients of all stages
      (84% male; median age of 64 years), two BRM polymorphisms were genotyped. Cox
      proportional hazards models, adjusted for known prognostic variables, estimated
      the association of polymorphisms with OS. CONCLUSIONS: BRM polymorphisms were
      associated with OS in EAC in this study. Validation studies are warranted.

PMID- 28427212
TI  - High Myc expression and transcription activity underlies intra-tumoral
      heterogeneity in triple-negative breast cancer.
AB  - We have previously identified a novel intra-tumoral dichotomy in triple-negative
      breast cancer (TNBC) based on the differential responsiveness to a reporter
      containing the Sox2 regulatory region-2 (SRR2), with reporter responsive (RR)
      cells being more stem-like than reporter unresponsive (RU) cells. Using
      bioinformatics, we profiled the protein-DNA binding motifs of SRR2 and identified
      Myc as one of the potential transcription factors driving SRR2 activity. In
      support of its role, Myc was found to be highly expressed in RR cells as compared
      to RU cells. Enforced expression of MYC in RU cells resulted in a significant
      increase in SRR2 activity, Myc-DNA binding, proportion of cellsexpressing
      CD44+/CD24-, chemoresistance and mammosphere formation. Knockdown of Myc using
      siRNA in RR cells led to the opposite effects. We also found evidence that the
      relatively high ERK activation in RR cells contributes to their high expression
      of Myc and stem-like features. Using confocal microscopy and patient samples, we
      found a co-localization between Myc and CD44 in the same cell population. Lastly,
      a high proportion of Myc-positive cells in tumors significantly correlated with a
      short patient survival. In conclusion, inhibition of the MAPK/ERK/Myc axis may be
      an effective approach in eliminating stem-like cells in TNBC.

PMID- 28427213
TI  - Clinical benefit of continuing crizotinib therapy after initial disease
      progression in Chinese patients with advanced ALK-rearranged non-small-cell lung
      cancer.
AB  - PURPOSE: Although most patients with ALK-positive non-small-cell lung cancer
      (NSCLC) who benefit from treatment with crizotinib ultimately develop progressive
      disease (PD), continuing crizotinb beyond the initial PD (CBPD) in these patients
      may be beneficial. In this study, we investigated whether Chinese patients with
      advanced ALK-positive NSCLC benefit from CBPD, and whether any factors are
      predictive of a longer post-initial progression-free survival time (PFS2).
      MATERIALS AND METHODS: Data on 33 patients with ALK-positive NSCLC who achieved
      disease control with crizotinib were analyzed retrospectively. The impact of
      continued crizotinib therapy on the patients' PFS2 time was assessed after
      adjusting for potential confounding factors. RESULTS: With initial crizotinib
      therapy, the objective response rate (ORR) and median PFS time (PFS1) in the 33
      patients were 63.6% and 8.6 months, respectively. With continued crizotinib
      therapy after documentation of PD, the median PFS2 for all 33 patients was 16
      weeks, and in those with CNS progression but systemic disease control it was 30
      weeks. Patients who received local therapy after disease progression had a
      significantly longer PFS2 compared with those who did not (P = 0.039).
      Multivariable Cox regression analysis showed that the PFS1 with initial
      crizotinib treatment and local therapy were independent predictors of PFS2.
      DISCUSSION: This study provides further evidence of the benefit of continuing
      crizotinib therapy in Chinese patients with progressive ALK-positive NSCLC.
      Patients with a longer PFS1 and those who received local brain therapy would have
      a longer period of continuing crizotinib.

PMID- 28427216
TI  - The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the
      survival benefit and severe late toxicities of re-irradiation with intensity
      modulated radiotherapy.
AB  - BACKGROUND: Effective treatments for patients with advanced locally recurrent
      nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine
      the potential benefits from re-irradiation by intensity-modulated radiotherapy
      (IMRT) on survival and the effects of severe late toxicities. METHODS: A
      retrospective study was conducted in 245 patients diagnosed with locally
      recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data
      was colletedand factors associated with survival and severe late toxicities were
      analyzed. RESULTS: The 5-year local-regional failure-free survival, distant
      failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%,
      respectively. The presence of severe late complications, recurrent T4 disease and
      gross tumor volume >30 cm3 were associated with poor survival. The incidences of
      mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were
      22.0%, 14.6%, 27.0% and 14.6% respectively. CONCLUSIONS: Re-irradiation with IMRT
      is an effective choice in patients with locally recurrent T3-T4 NPC. However, the
      survival benefits can be partly offset by severe late complications and optimum
      treatments in these patients remain a challenge.

PMID- 28427222
TI  - Prognostic role of matrix metalloproteinases in bladder carcinoma: a systematic
      review and meta-analysis.
AB  - Recent studies have shown that matrix metalloproteinases (MMPs) might be a
      biomarker for predicting outcomes of bladder cancer. However, the prognostic
      value of overexpression of MMPs in bladder cancer is debatable and the studies
      are inconsistent. Therefore, this meta-analysis was performed to clarify the
      specific association and prognostic value of overexpression of MMPs in bladder
      carcinoma. Relevant studies were identified by searching PubMed, EMBASE, and the
      Web of Science. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs)
      for disease-specific survival (DSS), overall survival (OS), disease/recurrence
      free survival (DFS/RFS), and progression/metastasis-free survival (PFS/MFS) were
      analyzed to determine the prognostic value of MMPs. In total, eighteen applicable
      studies were included in this meta-analysis. We found that high expression of
      MMPs significantly correlated with a poor DSS and OS (HR=1.66; 95% CI = 1.38-2.01
      and HR= 1.67; 95%CI= 1.26-2.22). MMPs also predicted tumor progression and
      metastasis with a pooled HR of 3.03 (95% CI 1.98-4.64). However, high MMPs
      expression had no pivotal impact on DFS/RFS (HR= 1.21; 95% CI= 0.96-1.53). With
      the purpose of better understanding the prognostic role of MMPs in patients wirh
      bladder carcinoma, we carried out this systematic review and meta-analysis.

PMID- 28427223
TI  - Isoform expression patterns of EPHA10 protein mediate breast cancer progression
      by regulating the E-Cadherin and beta-catenin complex.
AB  - Overexpression of EPHA10 protein was reported in concomitance with clinical
      severity of breast cancer. In this study, we annotate overexpression of EPHA10
      protein with changes of isoform expression as EphA10s (EPHA10 isoform 2) and
      EphA10 (EPHA10 isoform 3). In the process of malignant transformation, secretory
      protein EphA10s is in low expression, and pseudo-kinase EphA10 is overexpressed
      and cytoplasmically enriched. Down-regulated EphA10s blunts stabilization of
      membrane-associate beta-catenin via the interaction with ephrin A5. Cytoplasmic
      EphA10 maintains phosphorylation of E-cadherin. Restoring isoform expression
      pattern by up-regulated EphA10s and down-regulated cytoplasmic EphA10 inhibits
      cell invasion and lymph node metastasis by strengthening the stability of the
      complex of E-cadherin and beta-catenin in membrane. Taken together, we defined
      the novel interaction via expression patterns of EphA10s and EphA10 that promote
      malignant transformation of breast cancer, and demonstrated the potential benefit
      in clinical usage.

PMID- 28427225
TI  - Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient
      tumour cells with hyperthermia.
AB  - BACKGROUND: Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA
      single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA
      double strand breaks, which are generally repaired by homologous recombination
      (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally
      sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be
      temporarily inhibited by hyperthermia, thereby inducing synthetic lethal
      conditions in every tumor type. Since cisplatin is successfully used combined
      with hyperthermia (thermochemotherapy), we investigated the effectiveness of
      combining PARP1-i with thermochemotherapy. RESULTS: The in vitro data demonstrate
      a decreased in cell survival after addition of PARP1-i to thermochemotherapy,
      which can be explained by increased DNA damage induction and less DSB repair.
      These in vitro findings are in line with in vivo model, in which a decreased
      tumor growth is observed upon addition of PARP1-i. MATERIALS AND METHODS:
      Survival of three HR-proficient cell lines after cisplatin, hyperthermia and/or
      PARP1-i was studied. Cell cycle analyses, quantification of gamma-H2AX foci and
      apoptotic assays were performed to understand these survival data. The effects of
      treatments were further evaluated by monitoring tumor responses in an in vivo rat
      model. CONCLUSIONS: Our results in HR-proficient cell lines suggest that PARP1-i
      combined with thermochemotherapy can be a promising clinical approach for all
      tumors independent of HR status.

PMID- 28427224
TI  - Ponatinib promotes a G1 cell-cycle arrest of merlin/NF2-deficient human schwann
      cells.
AB  - Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals
      to multiple benign tumors of the central and peripheral nervous systems,
      including vestibular schwannomas. Currently, there are no FDA approved drug
      therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor
      gene leads to activation of multiple mitogenic signaling cascades, including
      platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The
      goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC
      inhibitor, reduced proliferation and/or survival of merlin-deficient human
      Schwann cells (HSC). Merlin-deficient HSC had higher levels of phosphorylated
      PDGFRalpha/beta, and SRC than merlin-expressing HSC. A similar phosphorylation
      pattern was observed in phospho-protein arrays of human vestibular schwannoma
      samples compared to normal HSC. Ponatinib reduced merlin-deficient HSC viability
      in a dose-dependent manner by decreasing phosphorylation of PDGFRalpha/beta, AKT,
      p70S6K, MEK1/2, ERK1/2 and STAT3. These changes were associated with decreased
      cyclin D1 and increased p27Kip1levels, leading to a G1 cell-cycle arrest as
      assessed by Western blotting and flow cytometry. Ponatinib did not modulate ABL,
      SRC, focal adhesion kinase (FAK), or paxillin phosphorylation levels. These
      results suggest that ponatinib is a potential therapeutic agent for NF2
      associated schwannomas and warrants further in vivo investigation.

PMID- 28427226
TI  - MicroRNA-152 regulates immune response via targeting B7-H1 in gastric carcinoma.
AB  - MiR-152 has been reported may be involved in carcinogenesis in gastric cancer.
      However, its role has not been comprehensively investigated in gastric cancer. We
      found miR-152 in human gastric cancer tissues were significantly lower than that
      in matched adjacent normal tissues. Meanwhile, lower miR-152 was also found in
      gastric cancer cell lines. The stage, tumor size and lymph node metastasis rate
      were significant higher in low-miR-152 group in clinical patients. Furthermore,
      there was a marked correlation between the levels of miR-152 and B7-H1 mRNA in
      gastric cancer tissues. Mechanistically, miR-152 directly bind to B7-H1 3'
      untranslated region in gastric cancer cell and inhibited B7-H1 expression.
      Functional study demonstrated that elevation of miR-152 enhanced T cells
      proliferation and effector cytokines production via inhibiting B7-H1/PD-1
      pathway. In conclusion, our work identified a novel mechanism by which immune
      response is increased by expression of miR-152 via targeting B7-H1. MiR-152 may
      be a potential therapeutic approach for gastric cancer.

PMID- 28427228
TI  - miR-29a regulated ER-positive breast cancer cell growth and invasion and is
      involved in the insulin signaling pathway.
AB  - Increasing amounts of evidence show that insulin can activate different insulin
      signaling pathways to promote breast cancer growth and invasion. miR-29a plays
      crucial roles in decreasing glucose-stimulated insulin secretion, as well as in
      regulating breast cancer cell proliferation and EMT. However, the mechanism
      responsible for the regulatory effects of miR-29a on breast cancer growth and
      invasion and the relationship between these effects and insulin signaling remains
      unclear. Herein, we showed that human insulin increased miR-29a expression in ER
      positive breast cancer cells and that miR-29a facilitated the ability of insulin
      to promote breast cancer cell proliferation and migration. We found that miR-29a
      induced cell proliferation and metastasis acceleration occurred primarily through
      ERK phosphorylation. The IGF-1R is the upstream target gene of miR-29a, while
      CDC42 and p85alpha are the downstream target genes of miR-29a. These results have
      provided us with information regarding the molecular mechanisms by which
      hyperinsulinemia promotes breast cancer occurrence and development and thus leads
      to a poor prognosis in breast cancer patients and indicate that miR-29a plays an
      important role in breast cancer development and invasion.

PMID- 28427227
TI  - High-dose ascorbate and arsenic trioxide selectively kill acute myeloid leukemia
      and acute promyelocytic leukemia blasts in vitro.
AB  - The use of high-dose ascorbate (ASC) for the treatment of human cancer has been
      attempted several decades ago and has been recently revived by several in vitro
      and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC,
      alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia
      (AML) and acute promyelocytic leukemia (APL). Leukemic cell lines and primary
      blasts from AML and APL patients were treated with graded concentrations of ASC,
      alone or in association with standard concentration (1 MUM) of ATO. The ASC/ATO
      combination killed myeloid blasts, including leukemic CD34+ cells, while sparing
      CD34+ progenitors obtained from normal cord blood and bone marrow. Actually,
      approximately one-third (11/36) of primary AML cases were highly sensitive to the
      ASC/ATO combination. The mechanism of cell killing appeared to be related to
      increased oxidative stress and overproduction of ROS in a non-quantitative
      fashion, which resulted in induction of apoptosis. These effects were reverted by
      the addition of the antioxidant N-Acetyl-Cysteine (NAC). In the APL NB4 model,
      ASC induced direct degradation of the PML and PML/RARA proteins via caspase
      activation, while the transcriptional repressor DAXX was recruited in re
      constituted PML nuclear bodies. Our findings encourage the design of pilot
      studies to explore the potential clinical benefit of ASC alone or in combination
      with ATO in advanced AML and APL.

PMID- 28427229
TI  - NADPH accumulation is responsible for apoptosis in breast cancer cells induced by
      fatty acid synthase inhibition.
AB  - Fatty acid synthase (FAS), as a key enzyme involved in de novo lipogenesis, is
      highly expressed in many cancers. FAS inhibition induces cell death in vivo and
      in vitro, rendering FAS as an attractive target for cancer therapy, but the
      defined mechanism is still not well understood. Herein, we confirmed that FAS was
      highly expressed in breast cancers and FAS inhibition by its inhibitors or
      knockdown induced apoptosis in breast cancer cells. Our results showed that a
      significantly high level of reactive oxygen species was induced but not
      responsible for apoptosis in breast cancer cells by FAS inhibition. Instead,
      NADPH accumulation resulting from FAS inhibition was found to stimulate NADPH
      oxidase to generate reactive oxygen species and highly associated with apoptosis
      induction. Suppression of NADPH oxidase almost totally blocked reactive oxygen
      species generation while significantly potentiated the in vitro and in vivo
      killing of breast cancers by FAS inhibition. Taken together, these data suggest
      that FAS plays a critical role in maintaining cellular redox homeostasis and its
      inhibition leads to NADPH accumulation-mediated apoptosis. Our finding may
      provide new insights into cancer metabolism and aid in designing effective
      anticancer treatments.

PMID- 28427230
TI  - Deguelin inhibits non-small cell lung cancer via down-regulating Hexokinases II
      mediated glycolysis.
AB  - Hexokinases II (HK2) is a hub in the regulation of cancer cell glycolysis. Here
      we reported deguelin, a natural compound which has been studied in various tumor
      types, has a profound anti-tumor effect on human non-small cell lung cancer
      (NSCLC) via directly down-regulating of glycolysis. In NSCLC cell lines and
      primary NSCLC tissue, we found HK2 is overexpressed. Deguelin treatment markedly
      inhibited anchorage-dependent and independent growth of NSCLC cell lines. We
      revealed that deguelin exposure impaired glucose metabolism by inhibiting Akt
      mediated Hexokinase II expression, overexpression of constitutively activated
      Akt1 substantially rescued deguelin-induced glycolysis suppression. Moreover,
      deguelin suppressed HK2 presence on mitochondrial outer membrane and induced
      apoptosis. The in vivo data indicated that deguelin prominently restrained tumor
      development in a xenograft mouse model. Thus, deguelin appears to be a promising
      new therapeutic agent for lung cancer and may be considered for further studies
      in other animal models and in clinical trials.

PMID- 28427231
TI  - Histopathologic tumor invasion of superior mesenteric vein/ portal vein is a poor
      prognostic indicator in patients with pancreatic ductal adenocarcinoma: results
      from a systematic review and meta-analysis.
AB  - BACKGROUND: The impact of histopathologic tumor invasion of the superior
      mesenteric vein (SMV)/portal vein (PV) on prognosis in patients with pancreatic
      ductal adenocarcinoma (PDAC) after pancreatectomy remains controversial. A meta
      analysis was performed to assess this issue. RESULTS: Eighteen observational
      studies comprising 5242 patients were eligible, of whom 2199 (41.9%) patients
      received SMV/PV resection. Histopathologic tumor invasion was detected in 1218
      (58.1%) of the 2096 resected SMV/PV specimens. SMV/PV invasion was associated
      with higher rates of poor tumor differentiation (P = 0.002), lymph node
      metastasis (P < 0.001), perineural invasion (P < 0.001), positive resection
      margins (P = 0.004), and postoperative tumor recurrence (P < 0.001). SMV/PV
      invasion showed a significantly negative effect on survival in total patients who
      underwent pancreatectomy with and without SMV/PV resection (hazard ratio [HR]:
      1.21, 95% confidence interval [CI]: 1.08-1.35; P = 0.001) and in patients who
      underwent pancreatectomy with SMV/PV resection (HR: 1.88, 95% CI, 1.48-2.39; P <
      0.001). MATERIALS AND METHODS: A systematic literature search was performed to
      identify articles published from January 2000 to August 2016. Data were pooled
      for meta-analysis using Review Manager 5.3. CONCLUSIONS: Histopathologic tumor
      invasion of the SMV/PV is associated with more aggressive biologic behavior and
      could be used as an indicator of poor prognosis after PDAC resection.

PMID- 28427232
TI  - Embryonic signature distinguishes pediatric and adult rhabdoid tumors from other
      SMARCB1-deficient cancers.
AB  - Extra-cranial rhabdoid tumors (RT) are highly aggressive malignancies of infancy,
      characterized by undifferentiated histological features and loss of SMARCB1
      expression. The diagnosis is all the more challenging that other poorly
      differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas
      (ES), renal medullary carcinomas (RMC) or undifferentiated chordomas (UC).
      Moreover, late cases occurring in adults are now increasingly reported, raising
      the question of differential diagnoses and emphasizing nosological issues. To
      address this issue, we have analyzed the expression profiles of a training set of
      32 SMARCB1-deficient tumors (SDT), with ascertained diagnosis of RT (n = 16, all
      < 5 years of age), ES (n = 8, all > 10 years of age), UC (n = 3) and RMC (n = 5).
      As compared with other SDT, RT are characterized by an embryonic signature, and
      up-regulation of key-actors of de novo DNA methylation processes. Using this
      signature, we then analysed the expression profiling of 37 SDT to infer the
      appropriate diagnosis. Thirteen adult onset tumors showed strong similarity with
      pediatric RT, in spite of older age; by exome sequencing, these tumors also
      showed genomic features indistinguishable from pediatric RT. In contrary, 8
      tumors were reclassified within carcinoma, ES or UC categories, while the
      remaining could not be related to any of those entities. Our results demonstrate
      that embryonic signature is shared by all RT, whatever the age at diagnosis; they
      also illustrate that many adult-onset SDT of ambiguous histological diagnosis are
      clearly different from RT. Finally, our study paves the way for the routine use
      of expression-based signatures to give accurate diagnosis of SDT.

PMID- 28427234
TI  - Diversity of the association of serum levels and genetic variants of MHC class I
      polypeptide-related chain A with liver fibrosis in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Genetic variants of MHC class I polypeptide-related chain A
      (MICA) at rs2596542 have been associated with hepatocellular carcinoma. The
      linkage between serum MICA (sMICA) and liver fibrosis in chronic hepatitis C is
      elusive. RESULTS: Linear regression analysis revealed that sMICA were
      independently correlated to alpha-fetoprotein (beta: 0.149; 95% confidence
      interval [CI]: 0.001, 0.003; P = 0.007)and MICA rs2596542 GG genotype (beta:
      0.209; 95% CI: 0.153, 0.483; P < 0.001). While patients were stratified by MICA
      genetic variants, advanced fibrosis was the only factor independently correlated
      to sMICA among A allele carriers (beta: 0.234; 95% CI: 0.107, 0.543; P = 0.004)
      but not among non-A allele carriers. Logistic regression analysis revealed that
      factors associated with advanced liver fibrosis was sMICA (OR/CI: 2.996/1.428
      6.287, P = 0.004) and platelet counts (OR/CI: 0.988/0.982-0.994, P < 0.001) in
      MICA rs2596542 A allele carriers. sMICA > 50 pg/mL provided a positive predictive
      value of 72 % in predicting advanced liver fibrosis (F3-4) and of 90% in
      significant fibrosis (> F2) in MICA rs2596542 A allele carriers. MATERIALS AND
      METHODS: Serum level and single nucleotide polymorphism at rs2596542 of MICA were
      tested for the association with liver fibrosis in 319 biopsy proven chronic
      hepatitis C patients. CONCLUSIONS: Levels of sMICA were highly correlated to
      liver disease severity in chronic hepatitis C patients who carried the MICA
      rs738409 A allele. Patients possessing the genetic predisposition had a higher
      likelihood of progressed liver fibrosis if they expressed higher sMICA levels.

PMID- 28427233
TI  - Assessment of the interlaboratory variability and robustness of JAK2V617F
      mutation assays: A study involving a consortium of 19 Italian laboratories.
AB  - To date, a plenty of techniques for the detection of JAK2V617F is used over
      different laboratories, with substantial differences in specificity and
      sensitivity. Therefore, to provide reliable and comparable results, the
      standardization of molecular techniques is mandatory.A network of 19 centers was
      established to 1) evaluate the inter- and intra-laboratory variability in
      JAK2V617F quantification, 2) identify the most robust assay for the
      standardization of the molecular test and 3) allow consistent interpretation of
      individual patient analysis results. The study was conceived in 3 different
      rounds, in which all centers had to blindly test DNA samples with different
      JAK2V617F allele burden (AB) using both quantitative and qualitative assays.The
      positivity of samples with an AB < 1% was not detected by qualitative assays.
      Conversely, laboratories performing the quantitative approach were able to
      determine the expected JAK2V617F AB. Quantitative results were reliable across
      all mutation loads with moderate variability at low AB (0.1 and 1%; CV = 0.46 and
      0.77, respectively). Remarkably, all laboratories clearly distinguished between
      the 0.1 and 1% mutated samples.In conclusion, a qualitative approach is not
      sensitive enough to detect the JAK2V617F mutation, especially at low AB. On the
      contrary, the ipsogen JAK2 MutaQuant CE-IVD kit resulted in a high, efficient and
      sensitive quantification detection of all mutation loads. This study sets the
      basis for the standardization of molecular techniques for JAK2V617F
      determination, which will require the employment of approved operating procedures
      and the use of certificated standards, such as the recent WHO 1st International
      Reference Panel for Genomic JAK2V617F.

PMID- 28427235
TI  - Catan-ionic hybrid lipidic nano-carriers for enhanced bioavailability and anti
      tumor efficacy of chemodrugs.
AB  - To date there has not been any report on catan-ionic hybrid lipidic nano
      carriers, let alone a report on applying them to deliver insoluble anti-tumor
      drugs. Catan-ionic hybrid lipidic nano-carriers containing curcumin (CUR-C-HLN)
      inherit the merits of catan-ionic systems, hybrid lipidic systems and nano
      structured carriers (the second-generation substitute of solid lipidic nano
      systems). Catan-ionic surfactants increased microvesicle stabilization by
      producing unordered isometric clusters, enhanced absorptive amount as an
      inhibitor of enzyme and protein, improved tumor accumulation by cellular
      endocytosis and membranous fusion; hybrid lipids helped to obtain high drug
      content and low leakage by forming a less-organized matrix arrangement. CUR-C-HLN
      favorably changed absorptive and pharmacokinetic properties after oral and/or
      intravenous administrations; improved cell growth inhibition, apoptotic inducing
      and anti-invasion effects; enhanced antitumor efficiency and reduced cancerous
      growth. Catan-ionic hybrid lipidic nano-carriers provide an alternative good
      choice for effective delivery of anticancerous chemodrugs.

PMID- 28427236
TI  - Combined effects of glutathione S-transferase M1 and T1 polymorphisms on risk of
      lung cancer: Evidence from a meta-analysis.
AB  - Many studies have reported an association between the glutathione S-transferase
      M1 null and T1 null polymorphisms and lung cancer risk. However, the combined
      effects of GSTM1 null and GSTT1 null polymorphisms have not been reported
      previously. We, therefore, performed a meta-analysis to investigate the combined
      effects. 40 publications with 44 case-control studies were selected in the meta
      analysis, including 13,706 cases and 13,093 controls. Significant association was
      observed between the combined effects of GSTM1 and GSTT1 polymorphisms and lung
      cancer risk when all the eligible studies were pooled into the meta-analysis.
      When we performed subgroup analysis, significantly increased lung cancer risk was
      observed in Caucasians (- - vs. + + : OR = 1.23, 95% CI: 1.07 to 1.41), Asians (-
      - vs.- +: OR = 1.24, 95% CI: 1.10 to 1.41; recessive model: OR = 1.45, 95% CI:
      1.19 to 1.77; dominant model: OR = 1.53, 95% CI: 1.24 to 1.90), Indians (- - vs.
      + + : OR = 2.53, 95% CI: 1.61 to 3.98; recessive model: OR = 1.69, 95% CI: 1.07
      to 2.67; dominant model: OR = 2.11, 95% CI: 1.36 to 3.28), hospital-based
      studies, and population-based studies. In summary, this meta-analysis indicates
      that the combined effects of the GSTM1 and GSTT1 polymorphisms are associated
      with increased lung cancer risk in Asians, Caucasians, and Indians.

PMID- 28427237
TI  - Oxidative DNA double strand breaks and autophagy in the antitumor effect of
      sterically hindered platinum(II) complexes in NSCLCs.
AB  - A series of novel platinum(II) complexes with (1R,2R)-N1,N2-diisobutyl-1,2
      diaminocyclohexane as a carrier ligand, while N1,N2-diisobutyl moiety serving as
      steric hindrance were designed, synthesized and characterized. The in vitro
      biological assays demonstrated that complex 3 had increased cytotoxicity against
      lung cancer cells, especially non-small-cell lung cancer (NSCLC) compared to its
      mono-substituted complex 3a, indicating that the sterically hindered alkyl
      moieties have significant influences on its antitumor property. However, the
      mechanism still remains unclear. The further studies revealed that complex 3
      could induce ROS overproduction, severe DNA double strands breaks and inhibit the
      activation of DNA damage repair proteins within nucleus, leading to cell-cycle
      arrest and cell death. Moreover, complex 3 could induce autophagy via the
      accumulation of autophagic vacuoles and alterations of autophagic protein
      expression. Interestingly, the ROS scavengers, N-acetyl-cysteine (NAC) could
      reverse complex 3-induced DNA double strands breaks and autophagic responses more
      significantly compared to complex 3a. The results demonstrated that the ROS
      generation plays an important role in the DNA double strands breaks and
      autophagic responses in the antitumor effect of complex 3 with N1,N2-diisobutyl
      moiety. Our study offered a novel therapeutic strategy and put new insights into
      the anticancer research of the complexes with N1,N2-diisobutyl moiety served as
      steric hindrance.

PMID- 28427238
TI  - Clinical features and treatment outcome of non-small cell lung cancer (NSCLC)
      patients with uncommon or complex epidermal growth factor receptor (EGFR)
      mutations.
AB  - INTRODUCTION: Tyrosine-kinase inhibitors (TKIs) represent the best treatment for
      advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon
      21 epidermal growth factor receptor mutation (EGFRm). This is an observational
      study investigating epidemiology, clinical features and treatment outcome of
      NSCLC cases harbouring rare/complex EGFRm. RESULTS: Among 764 non-squamous NSCLC
      cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients
      receiving first-line TKIs (N = 17) achieved median Progression Free Survival
      (PFS) and Overall Survival (OS) of 53 (IC 95%, 2-105) and 84 (CI 95%, 27-141)
      weeks respectively, without significant covariate impact. Response Rate and
      Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19
      mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20
      mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs
      were globally well tolerated. MATERIALS AND METHODS: A retrospective review of
      advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center
      between 2010 and 2015 was performed. Additional molecular pathways disregulation
      was explored in selected cases, through MassARRAY analysis. CONCLUSIONS: Peculiar
      clinical features and lower TKIs sensitivity of uncommon/complex compared with
      common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome,
      while the optimal treatment of exon 18 and 20 mutations should be further
      clarified.

PMID- 28427239
TI  - Foxo3a-dependent Bim transcription protects mice from a high fat diet via
      inhibition of activation of the NLRP3 inflammasome by facilitating autophagy flux
      in Kupffer cells.
AB  - BACKGROUND: The role of Foxo3a in the regulation of autophagy flux and activation
      of the NLRP3 inflammasome in KCs suffering from HFD conditions is unknown.
      RESULTS: Up-regulation of Foxo3a restored autophagy flux and dampened the
      activation of the NLRP3 inflammasome in KCs stimulated with PA and LPS. In
      contrast, down-regulation of Foxo3a increased blockage of autophagy flux and
      promoted NLRP3 inflammasome activation. Additionally, mRNA levels of Bim were
      significantly changed with the alteration of Foxo3a in KCs under PA and LPS
      stimulation among foxo3a targeted genes. Overexpression of Bim restored autophagy
      influx and attenuated NLRP3 inflammasome pathway activation. In addition,
      autophagy formation was restored, and activation of NLRP3 inflammasome was
      inhibited in KCs isolated from mice treated with Iturin A and fed with a HFD.
      MATERIALS AND METHODS: Autophagy flux in KCs and activation levels of NLRP3
      inflammasome were evaluated after altering the expression of Foxo3a in KCs before
      stimulation with PA and LPS. Additionally, various target genes of Foxo3a were
      measured in KCs pretreated with an agonist (Iturin A) or inhibitor (SC97) of
      Foxo3a after KCs stimulation with PA and LPS in order to hunt for targets of
      Foxo3a. Activation levels of NLRP3 inflammasome in isolated KCs, as well as
      autophagy flux, were measured after mice were treated with Iturin A and fed with
      a HFD for 16 weeks. CONCLUSIONS: Foxo3a restores autophagy flux and attenuates
      the activation of the NLRP3 inflammasome by promoting the transcription of Bim,
      suggesting a potential therapeutic target in NAFLD and other obesity-related
      diseases.

PMID- 28427241
TI  - EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and
      endoplasmic reticulum stress.
AB  - Diabetic nephropathy (DN) is a progressive kidney disease due to glomerular
      capillary damage in diabetic patients. Endoplasmic reticulum (ER) stress caused
      by reactive oxygen species (ROS) is associated with DN progression. Epidermal
      growth factor receptor (EGFR) mediates oxidative stress and damage of
      cardiomyocytes in diabetic mice. Here we demonstrated that AG1478, a specific
      inhibitor of EGFR, blocked EGFR and AKT phosphorylation in diabetic mice.
      Oxidative stress and ER stress markers were eliminated after AG1478
      administration. AG1478 decreased pro-fibrotic genes TGF-beta and collagen IV.
      Furthermore, we found that high glucose (HG) induced oxidative stress and ER
      stress, and subsequently increased ATF4 and CHOP. These changes were eliminated
      by either AG1478 or ROS scavenger N-acetyl-L-cysteine (NAC) administration. These
      results were confirmed by knock-down approaches in renal mesangial SV40 cells.
      However, AG1478, not NAC, reversed HG induced EGFR and AKT phosphorylation. These
      results suggest that EGFR/AKT/ROS/ER stress signaling plays an essential role in
      DN development and inhibiting EGFR may serve as a potential therapeutic strategy
      in diabetic kidney diseases.

PMID- 28427240
TI  - UBE2T knockdown inhibits gastric cancer progression.
AB  - Ubiquitin-conjugating enzymes (E2 enzymes) such as UBE2T target proteins for
      degradation via the proteasome. Here, we examined the effects of UBE2T on the
      progression of gastric cancer. UBE2T was highly expressed in gastric tumors and
      gastric cancer cells. siRNA-mediated suppression of UBE2T inhibited gastric
      cancer cell proliferation and colony formation by promoting cell cycle arrest at
      G2/M phase and increasing apoptosis. Suppression of UBE2T also attenuated the
      invasive and metastatic abilities of gastric cancer cells by altering expression
      of epithelial-mesenchymal transition (EMT)-related factors. A xenograft model in
      which nude mice were injected with UBE2T knockdown human gastric cancer cells
      confirmed that suppression of UBE2T also decreased tumor formation and growth in
      vivo. Expression levels of CCND1, Phospho-GSK3B, WNT family members, and MYC were
      all affected by UBE2T knockdown. These results suggest that UBE2T plays a
      critical role in gastric cancer, and that it may serve as a useful prognostic
      biomarker and therapeutic target in gastric cancer patients.

PMID- 28427242
TI  - Epidermal growth factor receptor variant III in head and neck squamous cell
      carcinoma is not relevant for targeted therapy and irradiation.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) is an important regulator
      of cell growth and survival, and is highly variable in tumor cells. The most
      prevalent variation of the EGFR extracellular domain is the EGFR variant III
      (EGFRvIII). Some studies imply that EGFRvIII may be responsible for the poor
      response to the monoclonal EGFR-antibody Cetuximab, used therapeutically in head
      and neck squamous cell carcinoma (HNSCC). Due to inconsistent data in the
      literature regarding EGFRvIII prevalence and clinical relevance in HNSCC,
      especially its predictive value, we examined EGFRvIII-transfected cell lines and
      patient tissue samples. RESULTS: In contrast to other recent publications, we
      were able to demonstrate EGFRvIII expression in HNSCC. However, we noted that the
      different detection methods yielded inconsistent results. Furthermore, our
      EGFRvIII transfected and EGFR wild type cell lines exhibited similar
      characteristics and response rates in the performed in vitro experiments.
      MATERIALS AND METHODS: We conducted various inhibition and combined irradiation
      experiments using three EGFRvIII-transfected cell lines. Moreover, a patient
      cohort of 149 cases consisting of formalin fixed and paraffin embedded (FFPE) and
      fresh-frozen specimens was assayed via reverse transcriptase PCR (rtPCR) with gel
      electrophoresis and sequencing for EGFRvIII prevalence. In the rtPCR assays, we
      used five previously published EGFRvIII primers and EGFRvIII-positive
      glioblastoma tissue as a positive control. In addition, immunohistochemical
      staining was conducted. CONCLUSIONS: EGFRvIII can be detected in HNSCC patient
      samples. Nevertheless, the low prevalence and similar response rates to targeted
      drugs and irradiation in vitro cast doubt regarding the clinical relevance of
      EGFRvIII in HNSCC.

PMID- 28427243
TI  - USP22 drives colorectal cancer invasion and metastasis via epithelial-mesenchymal
      transition by activating AP4.
AB  - Ubiquitin specific peptidase 22 (USP22), a putative cancer stem cell marker, is
      overexpressed in liver metastases of colorectal cancer (CRC). However, the
      mechanism by which USP22 promotes CRC metastasis remains largely unknown. Here,
      we report that USP22 and AP4 are simultaneously overexpressed during TGF-beta1
      induced CRC cell epithelial-mesenchymal transition (EMT). USP22 up-regulation
      enhances CRC cell migration and invasion and EMT-related marker and AP4
      expression, but these effects are partly blocked by AP4 knockdown. In addition,
      USP22 binds to the promoter region of AP4 to activate its transcription. In vivo,
      elevated USP22 expression promotes CRC cell metastasis to the lungs in nude mice,
      as evidenced by the fact that CRC metastatic nodules stain deeply positive for
      USP22 and AP4. In human CRC tissues, the genes encoding USP22 and AP4 are
      overexpressed in metastatic liver lesions compared with primary cancer tissues,
      and their overexpression is significantly associated with poor CRC patient
      survival. These findings indicate that USP22 and AP4 may serve as prognostic
      markers for predicting the risk of developing distant metastases in CRC.

PMID- 28427245
TI  - The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC)
      on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation.
AB  - BACKGROUND: The voltage-dependent anion channels (VDAC) play an essential role in
      the cross talk between mitochondria and the rest of the cell. Their implication
      in cell life and cell death has been studied extensively in recent years. In this
      work we studied the impact of mitochondrial membrane (VDACs) on cell survival and
      response to X-ionizing radiation (IR) of human lymphoblastoid K562 cells.
      METHODS: The inhibition of VDACs was achieved by 4,4'-diisothiocyanostilbene-2,2'
      disulfonic acid (DIDS) inhibitor and in vitro experiments including clonogenity
      assay, UV-visible spectrophotometry, comet assay and FACS analysis were
      implemented. RESULTS: Inhibition of VDAC led to augmentation of IR-induced
      apoptosis and ROS production. Additionally, DIDS affected repair of IR-induced
      DNA strand breaks and was in line with both induction of apoptosis and caspase
      activity. The IR-induced NO production was potently reduced by inhibition of
      VDAC. CONCLUSION: Our results suggest that VDAC control cellular response to
      ionizing radiation through modulation of the ROS- and NO-dependent signaling
      pathways. Inhibition of VDAC with DIDS induced apoptosis in irradiated K562
      lymphoblastoid cells points at DIDS, as a promising agent to enhance the
      effectiveness of radiotherapy.

PMID- 28427244
TI  - Whole-genome expression analyses of type 2 diabetes in human skin reveal altered
      immune function and burden of infection.
AB  - Skin disorders are among most common complications associated with type 2
      diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk
      of infections and other T2DM-related skin disorders, their molecular mechanisms
      are largely unknown. This study aims to identify dysregulated genes and gene
      networks that are associated with T2DM in human skin. We compared the expression
      profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and
      race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx)
      database. RNA-Sequencing data indicates that diabetic skin is characterized by
      increased expression of genes that are related to immune responses (CCL20, CXCL9,
      CXCL10, CXCL11, CXCL13, and CCL18), JAK/STAT signaling pathway (JAK3, STAT1, and
      STAT2), tumor necrosis factor superfamily (TNFSF10 and TNFSF15), and infectious
      disease pathways (OAS1, OAS2, OAS3, and IFIH1). Genes in cell adhesion molecules
      pathway (NCAM1 and L1CAM) and collagen family (PCOLCE2 and COL9A3) are
      downregulated, suggesting structural changes in the skin of T2DM. For the first
      time, to the best of our knowledge, this pioneer analytic study reports
      comprehensive unbiased gene expression changes and dysregulated pathways in the
      non-diseased skin of T2DM patients. This comprehensive understanding derived from
      whole-genome expression profiles could advance our knowledge in determining
      molecular targets for the prevention and treatment of T2DM-associated skin
      disorders.

PMID- 28427246
TI  - Nanotechnology and Diabetic Wound Healing: A Review
AB  - Background and Objective: The incidence of diabetes has been on the rise and the
      rate of rise since the turn of this century has been phenomenal. One of the
      various battling issues faced by diabetics all over the globe is the management
      of diabetic wounds. Currently, there are several management strategies to deal
      with the treatment of diabetic wounds. The conventional methods have several
      limitations. One of the major limitations is the rate and progression of healing
      of a diabetic wound when adopting a conventional diabetic wound management
      therapy. Lately, several nano techniques and nano products have emerged in the
      market that offer promising results for such patients. The treatment outcomes are
      achieved more efficiently with such nanomedical products. Methods: This review
      attempts to consider the currently available nanotechnological applications in
      the management of diabetic wounds. We take a deeper look into the available
      nanotherapeutic agents and the different nanocarriers that could be used in the
      management of diabetic wound healing. Lately, researchers around the globe have
      started providing evidences on the effective use of such nanoparticles in various
      fields of Medicine extending from genetics to various other branches of medicine.
      This also includes the management of diabetic wounds. Conclusion: This paper
      discusses the challenges faced with these nanotherapies and nanoparticles with
      regard to the treatment of diabetic wounds.

PMID- 28427247
TI  - Molecular Testing of Lung Cancers.
AB  - Targeted therapies guided by molecular diagnostics have become a standard
      treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and
      anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best
      predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors,
      respectively. Besides EGFR and ALK, the list of druggable genetic alterations has
      been growing, including ROS1 rearrangements, RET rearrangements, and MET
      alterations. In this situation, pathologists should carefully manage clinical
      samples for molecular testing and should do their best to quickly and accurately
      identify patients who will benefit from precision therapeutics. Here, we grouped
      molecular biomarkers of lung cancers into three categories-mutations, gene
      rearrangements, and amplifications-and propose expanded guidelines on molecular
      testing of lung cancers.

PMID- 28427248
TI  - Caloric Restriction-Induced Extension of Chronological Lifespan Requires Intact
      Respiration in Budding Yeast.
AB  - Caloric restriction (CR) has been shown to extend lifespan and prevent cellular
      senescence in various species ranging from yeast to humans. Many effects of CR
      may contribute to extend lifespan. Specifically, CR prevents oxidative damage
      from reactive oxygen species (ROS) by enhancing mitochondrial function. In this
      study, we characterized 33 single electron transport chain (ETC) gene-deletion
      strains to identify CR-induced chronological lifespan (CLS) extension mechanisms.
      Interestingly, defects in 17 of these 33 ETC gene-deleted strains showed loss of
      both respiratory function and CR-induced CLS extension. On the contrary, the
      other 16 respiration-capable mutants showed increased CLS upon CR along with
      increased mitochondrial membrane potential (MMP) and intracellular adenosine
      triphosphate (ATP) levels, with decreased mitochondrial superoxide generation. We
      measured the same parameters in the 17 non-respiratory mutants upon CR. CR
      simultaneously increased MMP and mitochondrial superoxide generation without
      altering intracellular ATP levels. In conclusion, respiration is essential for
      CLS extension by CR and is important for balancing MMP, ROS, and ATP levels.

PMID- 28427249
TI  - Crystal Structure of the Regulatory Domain of AphB from Vibrio vulnificus, a
      Virulence Gene Regulator.
AB  - The transcriptional activator AphB has been implicated in acid resistance and
      pathogenesis in the food borne pathogens Vibrio vulnificus and Vibrio cholerae.
      To date, the full-length AphB crystal structure of V. cholerae has been
      determined and characterized by a tetrameric assembly of AphB consisting of a DNA
      binding domain and a regulatory domain (RD). Although acidic pH and low oxygen
      tension might be involved in the activation of AphB, it remains unknown which
      ligand or stimulus activates AphB at the molecular level. In this study, we
      determine the crystal structure of the AphB RD from V. vulnificus under aerobic
      conditions without modification at the conserved cysteine residue of the RD, even
      in the presence of the oxidizing agent cumene hydroperoxide. A cysteine to serine
      amino acid residue mutant RD protein further confirmed that the cysteine residue
      is not involved in sensing oxidative stress in vitro. Interestingly, an
      unidentified small molecule was observed in the inter-subdomain cavity in the RD
      when the crystal was incubated with cumene hydroperoxide molecules, suggesting a
      new ligand-binding site. In addition, we confirmed the role of AphB in acid
      tolerance by observing an aphB-dependent increase in cadC transcript level when
      V. vulnificus was exposed to acidic pH. Our study contributes to the
      understanding of the AphB molecular mechanism in the process of recognizing the
      host environment.

PMID- 28427250
TI  - [Escherichia coli pyomyositis among haematological patients, a pathology on
      increase].

PMID- 28427251
TI  - [Neuroborreliosis, 10-year experience in a tertiary hospital in northern Spain].

PMID- 28427252
TI  - Long non-coding RNA BRAF activated non-coding RNA as a potential novel molecular
      biomarker for metastasis and prognosis in various cancers.

PMID- 28427253
TI  - Meta-analysis of the correlation between the rs17401966 polymorphism in kinesin
      family member 1B and susceptibility to hepatitis B virus related hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: The association between the kinesin family member 1B (KIF1B)
      gene polymorphism and the risk of hepatitis B virus-related hepatocellular
      carcinoma (HCC) has been investigated in many peer-reviewed studies. However,
      scholars have failed to replicate these results in validation tests. The purpose
      of the present study was to explore whether the KIF1B rs17401966 polymorphism was
      associated with susceptibility to HCC. METHODS: The results of case-controlled
      studies on the correlation between the KIF1B rs17401966 polymorphism and HCC
      susceptibility were collected using Google Scholar and the EMBASE, PubMed and
      CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total
      of 12 cohorts were included in this study. RESULTS: The 12 cohorts were
      integrated, and the results showed that the rs17401966 polymorphism reduced the
      risk for HCC under the allele, heterozygous, homozygous, and dominant models but
      not under the additive or recessive models. Moreover, the merged results showed
      strong heterogeneity, and the cumulative meta-analysis results were unreliable. A
      genetic differentiation analysis of the 12 cohorts found different degrees of
      genetic differentiation between the 5 cohorts in Zhang et al.'s study and the
      cohorts in the other studies. We further divided the 12 study cohorts into 2
      subgroups based on fixation index value; however, the results of that analysis
      were inconsistent. CONCLUSIONS: The results of this meta-analysis were not able
      to verify the association between the KIF1B rs1740199 polymorphism and HCC risk.
      Therefore, a well-designed, large-scale, multicenter validation study is needed
      to confirm the relationship.

PMID- 28427254
TI  - Supplementing Rhodobacter sphaeroides in the diet of lactating Holstein cows may
      naturally produce coenzyme Q10-enriched milk.
AB  - OBJECTIVE: To examine the effects of Rhodobacter sphaeroides (R. sphaeroides)
      supplementation as a direct-fed microbial (DFM) on rumen fermentation in dairy
      cows and on coenzyme Q10 (CoQ10) transition into milk, an in vitro rumen
      simulation batch culture and an in vivo dairy cow experiment were conducted.
      METHODS: The characteristics of in vitro ruminal fermentation were investigated
      using rumen fluids from six cannulated Holstein dairy cows at 2 h post-afternoon
      feeding. A control treatment was included in the experiments based on a typified
      total mixed ration (TMR) for lactating dairy cows, which was identical to the one
      used in the in vivo study, plus R. sphaeroides at 0.1%, 0.3%, and 0.5% TMR dry
      matter. The in vivo study employed six ruminally cannulated lactating Holstein
      cows randomly allotted to either the control TMR (C-TMR) treatment or to a diet
      supplemented with a 0.5% R. sphaeroides culture (S-TMR, dry matter basis) ad
      libitum. The presence of R. sphaeroides was verified using denaturing gradient
      gel electrophoresis (DGGE) applied to the bacterial samples obtained from the in
      vivo study. The concentration of CoQ10 in milk and in the supernatant from the in
      vitro study was determined using high performance liquid chromatography. RESULTS:
      The results of the in vitro batch culture and DGGE showed that the concentration
      of CoQ10 significantly increased after 2 h of R. sphaeroides supplementation
      above 0.1%. When supplemented to the diet of lactating cows at the level of 0.5%,
      R. sphaeroides did not present any adverse effect on dry matter intake and milk
      yield. However, the concentration of CoQ10 in milk dramatically increased, with
      treated cows producing 70.9% more CoQ10 than control cows. CONCLUSION: The CoQ10
      concentration in milk increased via the use of a novel DFM, and R. sphaeroides
      might be used for producing value-added milk and dairy products in the future.

PMID- 28427255
TI  - Oligosaccharides are a key factor in prediction of amino acid digestibility in
      soybean meal of different origins when fed to growing pigs.
AB  - OBJECTIVE: The objective of this experiment was to determine apparent ileal
      digestibility (AID) and standardized ileal digestibility (SID) of crude protein
      (CP) and amino acid (AA) in 15 sources of soybean meal (SBM) produced from
      soybeans from different countries and subsequently to establish equations for
      predicting the AID and SID in SBM based on their chemical composition. METHODS:
      Eighteen barrows (57.9+/-6.1 kg) fitted with a simple T-cannula were allotted
      into three 6*6 Latin square designs. Each period comprised a 6-d adaption period
      followed by a 2-d collection of ileal digesta. The 15 test diets included SBM as
      a sole source of AA in the diet. Another nitrogen-free diet was used to measure
      basal endogenous losses of CP and AA. Chromic oxide (0.3%) was used as an inert
      marker in each diet. RESULTS: The AID of lysine in SBM from China and USA tended
      to be greater than in SBM from Brazil (p<0.10). The SID of valine and proline in
      SBM from China was greater than in SBM from Brazil (p<0.05). The SID of lysine,
      threonine, cysteine and glycine in SBM from China tended to be greater than in
      SBM from Brazil (p<0.10). From a stepwise regression analysis, a series of AID
      and SID prediction equations were generated. The best fit equations for lysine in
      SBM were: AID lysine = 1.16 sucrose-1.81 raffinose+82.10 (R2 = 0.69, p<0.01) and
      SID lysine = 1.14 sucrose-1.93 raffinose-0.99 ether extract (EE)+85.26 (R2 =
      0.77, p<0.01). CONCLUSION: It was concluded that under the conditions of this
      experiment, the oligosaccharides (such as sucrose and raffinose) can be used to
      predict the AID and SID of AA in SBM with reasonable accuracy.

PMID- 28427256
TI  - Effect of superdosing phytase on productive performance and egg quality in laying
      hens.
AB  - OBJECTIVE: An experiment was conducted to determine the effect of superdosing
      phytase on productive performance and egg quality in laying hens. METHODS: A
      total of 200 42-wk-old Hy-Line Brown laying hens were allotted into 1 of 5
      dietary treatments with 5 replicates consisting of 8 hens per replicate. The
      positive control (PC) and negative control diets (NC) were prepared based on the
      recommended P levels in layer diets. Supplemental phytase was added to the
      negative control diet at 10,000 (SD10), 20,000 (SD20), or 30,000 (SD30) fytase
      units (FTU)/kg. Productive performance was summarized for 6 weeks from 42 weeks
      to 47 weeks of age. Egg quality was assessed from 4 eggs per replicate randomly
      collected at the conclusion of the experiment. RESULTS: The SD20 treatment had
      greater (p<0.05) hen-day egg production than PC, NC, and SD10 treatment groups.
      There was no difference in hen-day egg production between SD20 and SD30 treatment
      groups. However, SD30 treatment had greater (p<0.05) hen-day egg production than
      PC treatment, but showed no difference in hen-day egg production as compared to
      NC and SD10 treatment groups. However, egg weight, egg mass, feed intake, and
      feed conversion ratio were not affected by dietary treatments. Egg quality
      including eggshell strength, eggshell color, egg yolk color, and haugh unit was
      not influenced by dietary treatments. CONCLUSION: Superdosing level of 20,000
      FTU/kg phytase in diets has a positive effect on egg production rate, but no
      beneficial effect on egg quality in laying hens.

PMID- 28427257
TI  - Effect of dietary calcium concentrations in low non-phytate phosphorus diets
      containing phytase on growth performance, bone mineralization, litter quality,
      and footpad dermatitis incidence in growing broiler chickens.
AB  - OBJECTIVE: An experiment was conducted to investigate the effect of dietary Ca
      concentrations in low non-phytate phosphorus (NPP) diets containing phytase on
      growth performance, bone mineralization, litter quality, and footpad dermatitis
      (FPD) incidence in growing broiler chickens. METHODS: A total of 1,800 21-day-old
      Ross 308 growing broiler chickens were allotted to 1 of 6 dietary treatments with
      6 replicated cages. Six diets were formulated to provide increasing Ca
      concentrations of 4.0, 5.0, 6.0, 7.0, 8.0, or 9.0 g/kg in diets. The
      concentrations of NPP in all diets were maintained at 3.0 g/kg, and phytase was
      supplemented to all diets at the level of 1,000 fytase units (FTU)/kg. At the end
      of the 14-d feeding trial, birds were euthanized for tibia sampling, and litter
      samples were collected from 3 areas in the cage. The FPD incidence was measured
      based on a 6-point scoring system. RESULTS: Dietary Ca concentrations had no
      effect on growth performance of growing broiler chickens. However, a tendency
      (linear, p = 0.05) for decreased feed efficiency was observed as dietary Ca
      concentrations were increased. The concentrations of Ca and P in the tibia of
      broiler chickens increased (linear and quadratic, p<0.01) with increasing Ca
      concentrations in low NPP diets containing phytase. Litter pH, moisture, and N
      contents were not affected by increasing Ca concentrations in low NPP diets
      containing phytase. However, a tendency (quadratic, p = 0.10) for increased FPD
      incidence with increasing dietary Ca concentrations was observed. CONCLUSION:
      Dietary Ca concentrations from 4.0 to 9.0 g/kg in low NPP diets containing
      phytase have little effects on growth performance of growing broiler chickens.
      However, Ca and P concentrations in the tibia are decreased if dietary Ca
      concentrations are less than 5.0 g/kg. The FPD incidence for growing broiler
      chickens may be decreased if less than 9.0 g/kg of Ca is included in diets.

PMID- 28427258
TI  - Application of random regression models for genetic analysis of 305-d milk yield
      over different lactations of Iranian Holsteins.
AB  - OBJECTIVE: During the last decade, genetic evaluation of dairy cows using
      longitudinal data (test day milk yield or 305- day milk yield) using random
      regression method has been officially adopted in several countries. The
      objectives of this study were to estimate covariance functions for genetic and
      permanent environmental effects and to obtain genetic parameters of 305-day milk
      yield over seven parities. METHODS: Data including 60,279 total 305-day milk
      yield of 17,309 Iranian Holstein dairy cows in 7 parities calved between 20 to
      140 months between 2004 and 2011. Residual variances were modeled by homogeneous
      and step functions with 7 and 10 classes. RESULTS: The results showed that a
      third order polynomial for additive genetic and permanent environmental effects
      plus a step function with 10 classes for the residual variance was the most
      adequate and parsimonious model to describe the covariance structure of the data.
      Heritability estimates obtained by this model varied from 0.17 to 0.28. The
      performance of this model was better than repeatability model. Moreover, 10
      classes of residual variance produce the more accurate result than 7 classes or
      homogeneous residual effect. CONCLUSION: A quadratic Legendre polynomial for
      additive genetic and permanent environmental effects with 10 step function
      residual classes are sufficient to produce a parsimonious model that explained
      the change in 305-day milk yield over consecutive parities of Iranian Holstein
      cows.

PMID- 28427259
TI  - Copper-Catalyzed Diaryl Ether Formation from (Hetero)aryl Halides at Low
      Catalytic Loadings.
AB  - Diaryl formation is achieved by coupling phenols and (hetero)aryl halides under
      the catalysis of CuI/N,N'-bis(2-phenylphenyl) oxalamide (BPPO) or CuI/N-(2
      phenylphenyl)-N'-benzyl oxalamide (PPBO) at 90  degrees C using DMF or MeCN as
      the solvent. Only 0.2-2 mol % CuI and ligand are required for complete
      conversion, which represents the lowest catalytic loadings for a general
      Cu/ligand-catalyzed diaryl ether formation.

PMID- 28427260
TI  - Real-Time Fluorescence Detection in Aqueous Systems by Combined and Enhanced
      Photonic and Surface Effects in Patterned Hollow Sphere Colloidal Photonic
      Crystals.
AB  - Hollow sphere colloidal photonic crystals (HSCPCs) exhibit the ability to
      maintain a high refractive index contrast after infiltration of water, leading to
      extremely high-quality photonic band gap effects, even in an aqueous
      (physiological) environment. Superhydrophilic pinning centers in a
      superhydrophobic environment can be used to strongly confine and concentrate
      water-soluble analytes. We report a strategy to realize real-time ultrasensitive
      fluorescence detection in patterned HSCPCs based on strongly enhanced
      fluorescence due to the photonic band-edge effect combined with wettability
      differentiation in the superhydrophobic/superhydrophilic pattern. The orthogonal
      nature of the two strategies allows for a multiplicative effect, resulting in an
      increase of two orders of magnitude in fluorescence.

PMID- 28427261
TI  - Hot Hole Photoelectrochemistry on Au@SiO2@Au Nanoparticles.
AB  - There is currently a worldwide need to develop efficient photocatalytic materials
      that can reduce the high-energy cost of common industrial chemical processes. One
      possible solution focuses on metallic nanoparticles (NPs) that can act as
      efficient absorbers of light due to their surface plasmon resonance. Recent work
      indicates that small NPs, when photoexcited, may allow for efficient electron or
      hole transfer necessary for photocatalysis. Here we investigate the mechanisms
      behind hot hole carrier dynamics by studying the photodriven oxidation of citrate
      ions on Au@SiO2@Au core-shell NPs. We find that charge transfer to adsorbed
      molecules is most efficient at higher photon energies but still present with
      lower plasmon energy. On the basis of these experimental results, we develop a
      simple theoretical model for the probability of hot carrier-adsorbate
      interactions across the NP surface. These results provide a foundation for
      understanding charge transfer in plasmonic photocatalytic materials, which could
      allow for further design and optimization of photocatalytic processes.

PMID- 28427262
TI  - Melting Proteins: Evidence for Multiple Stable Structures upon Thermal
      Denaturation of Native Ubiquitin from Ion Mobility Spectrometry-Mass Spectrometry
      Measurements.
AB  - Ion mobility and mass spectrometry techniques are coupled with a temperature
      controlled electrospray ionization source to follow the structural transitions of
      ubiquitin in aqueous solution (pH = 3) at elevated solution temperatures (T = 26
      96  degrees C). Changes in the charge state distribution are consistent with a
      two-state, cooperative unfolding transition having a melting temperature of Tm =
      71 +/- 2  degrees C, in agreement with prior measurements [ Wintrode , P. L. ;
      Makhatadze , G. I. ; Privalov , P. L. Proteins , 1994 , 18 , 246 - 253 ].
      However, analysis of ion mobility distributions reveals the two-state transition
      is a composite of transitions involving at least nine unique species: three
      native or native-like structures; two that appear to be equilibrium intermediates
      (i.e., populations of new conformers that form at elevated temperatures but
      subsequently disappear at higher temperatures); and four products observed at
      high temperatures, including the well-characterized ubiquitin A state, and two
      solution species that are differentiated based on a cis- or trans-configured
      Glu18-Pro19 peptide bond. These nine states vary in abundances by factors as
      large as ~103 over the range of solution temperatures. Although experimental
      melting transitions are conceived as a loss of well-defined structure leading to
      a random distribution of unstructured, denatured forms, the results provide
      evidence for new conformers having at least some well-defined structural elements
      are stabilized as temperature is increased.

PMID- 28427263
TI  - Laser-Induced Functionalization of Organo/Carbon Interfaces for Selective
      Adsorption of Au Nanoparticles in Microsized Domains.
AB  - Laser microprocessing of highly oriented pyrolytic graphite (HOPG) in conjunction
      with chemical functionalization routines is used to fabricate functional
      microsized domains. Infrared and Auger electron spectroscopy, contact angle
      measurements, and electron microscopy are used for characterization of laser
      fabricated structures. HOPG samples are coated with alkylsiloxane monolayers.
      Laser-induced bromination of coated HOPG samples in gaseous bromine is carried
      out using a microfocused laser beam at a wavelength of 514 nm and 1/e2 laser spot
      diameter of about 2 MUm. Subsequent azidation and amination results in functional
      domains with sizes in the range of 1.2 to 40 MUm and more. At low laser powers
      and irradiation times fully functionalized circular-shaped structures are formed.
      At high laser powers and irradiation times laser processing results in
      decomposition of the organic monolayer and substrate in the center of the
      structures yielding donut-shaped structures. After laser processing and chemical
      transformation Au nanoparticles are selectively adsorbed onto the functional
      domains. This provides an opportunity to build up functional nanoparticle
      microarrays on carbon-based materials, e.g., for applications in sensing and
      electrocatalysis.

PMID- 28427269
TI  - Spatially selective binding of green fluorescent protein on designed organosilane
      nanopatterns prepared with particle lithography.
AB  - A practical approach for preparing protein nanopatterns has been to design
      surface templates of nanopatterns of alkanethiols or organosilanes that will
      selectively bind and localize the placement of biomolecules. Particle lithography
      provides a way to prepare millions of protein nanopatterns with a few basic
      steps. For our nanopatterning strategy, organosilanes with methoxy and sulfhydryl
      groups were chosen as a surface template. Green fluorescent protein (GFP) was
      selected as a model for patterning. Areas of 2-[methoxy (polyethyleneoxy)6
      9propyl]trichlorosilane (MPT-silane) are effective as a matrix for resisting the
      attachment of proteins, whereas nanopatterns with sulfur groups provide reactive
      sites for binding linker groups to connect proteins. A protocol with particle
      lithography was designed to make a surface template of nanopatterns of (3
      mercaptopropyl)trimethoxysilane (MPTMS) surrounded by a methoxy terminated
      matrix. The sulfhydryl groups of the MPTMS nanopatterns were activated with a
      sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate linker. The
      activated regions of MPTMS furnished sites for binding GFP. Samples were
      characterized with atomic force microscopy after successive steps of the
      patterning protocol to evaluate the selectivity of protein binding. Direct views
      of the protein bound selectively to designated sites of MPTMS are presented, as
      evidence of robust and reproducible patterning. Nanoscale patterns of proteins
      can be used for surfaces of biochips and biosensors, and also for immunochemistry
      test platforms.

PMID- 28427270
TI  - Skin irritation testing of antimicrobial conjugated electrolytes.
AB  - Each year, the United States spends about $20 billion to treat people who have
      been infected with antibiotic resistant bacteria. Even so, the development of new
      antibiotics has slowed considerably since the mid-20th century. As a result,
      researchers are looking into developing synthetic compounds and materials with
      antimicrobial activities such as those made by the Schanze and Whitten groups
      [ACS Appl. Mater. Interfaces 3, 2820 (2011)]. Previously, they have demonstrated
      that poly(phenylene ethynylene) (PPE) based electrolytes and oligomeric end-only
      phenylene ethynylene (EO-OPE) based electrolytes possess strong biocidal
      activity. However, before the PPE and OPE can be used with humans, skin
      irritation tests are required to ensure their safety. In this work, in vitro skin
      assays are used to predict in vivo irritation. Tissues were conditioned for 24 h,
      exposed to test substances for 1 h, and then tested for viability using
      colorimetric and cytokine assays. Concentrations up to 50 MUg/ml were tested.
      Viability assays and cytokine (IL-1alpha) assays demonstrated that the two
      polymers, three symmetric oligomers, and three "end only" oligomers were
      nonirritants. In addition, electrospun mats consisting of several promising
      compounds, including poly(caprolactone), were evaluated. Therefore, all test
      substances are conservatively classified as nonirritants after a 1 h exposure
      time period.

PMID- 28427271
TI  - The value of pre- and post-neoadjuvant chemotherapy F-18 FDG PET/CT scans in
      breast cancer: comparison with MRI.
AB  - Background Accurate assessment of neoadjuvant chemotherapy (NAC) response with
      positron emission tomography/computed tomography (PET/CT) or magnetic resonance
      imaging (MRI) may provide appropriate operation guidelines for individual breast
      cancer patients. Purpose To compare the values of PET/CT and MRI for response
      evaluation following NAC in breast cancer patients. Material and Methods Thirty
      three consecutive patients who underwent NAC were included. PET/CT and MRI were
      performed before and one to four weeks after NAC. With response evaluation of
      PET/CT and MRI, patients with complete/partial responses on imaging studies were
      considered to be responders, and those showing stable/progressive disease non
      responders. Peak standardized uptake value corrected for lean body mass (SULpeak)
      and metabolic tumor volume (MTV) were measured from PET/CT, and unidimensional
      diameter (1D) and tumor volume (TV) from MRI. Reduction rates for each parameter
      were calculated (Delta%SULpeak, Delta%MTV, Delta%1D, and Delta%TV). The
      pathological response for NAC as reference was evaluated after surgical resection
      of the remaining tumor in the breast. Results We identified 17 pathological
      responders and 16 non-responders. PET/CT had lower specificity and accuracy, but
      higher sensitivity than MRI, although no significant difference was found between
      PET/CT and MRI. Following NAC, there were significant differences between
      pathological responders and non-responders in SULpeak ( P < 0.001), MTV ( P <
      0.001), 1D ( P = 0.0003), TV ( P = 0.038), Delta%SULpeak ( P = 0.001), Delta%MTV
      ( P < 0.001), Delta%1D ( P < 0.001), and Delta%TV ( P = 0.001). Conclusion PET/CT
      showed lower specificity and accuracy than MRI in evaluating responses to NAC,
      but both PET/CT and MRI parameters may have predictive value in distinguishing
      therapeutic responders and non-responders following NAC.

PMID- 28427272
TI  - Biological technologies for the remediation of co-contaminated soil.
AB  - Compound contamination in soil, caused by unreasonable waste disposal, has
      attracted increasing attention on a global scale, particularly since multiple
      heavy metals and/or organic pollutants are entering natural ecosystem through
      human activities, causing an enormous threat. The remediation of co-contaminated
      soil is more complicated and difficult than that of single contamination, due to
      the disparate remediation pathways utilized for different types of pollutants.
      Several modern remediation technologies have been developed for the treatment of
      co-contaminated soil. Biological remediation technologies, as the eco-friendly
      methods, have received widespread concern due to soil improvement besides
      remediation. This review summarizes the application of biological technologies,
      which contains microbial technologies (function microbial remediation and
      composting or compost addition), biochar, phytoremediation technologies, genetic
      engineering technologies and biochemical technologies, for the remediation of co
      contaminated soil with heavy metals and organic pollutants. Mechanisms of these
      technologies and their remediation efficiencies are also reviewed. Based on this
      study, this review also identifies the future research required in this field.

PMID- 28427273
TI  - Association of Exclusive Breastfeeding Duration With Systemic Inflammation
      Markers in Adolescents: A Cross-Sectional Study.
AB  - BACKGROUND: Breastfeeding duration has been associated with less low-grade
      inflammation in healthy adolescents, but there is scarce information regarding
      obese subjects. This study aimed to evaluate whether exclusive breastfeeding is
      related to serum concentrations of inflammatory markers in a population of
      Spanish adolescents. METHOD: A cross-sectional study was performed on 1,001
      adolescents (13.2 +/- 1.2 years) randomly recruited from schools in southeast
      Spain. Data on breastfeeding duration were collected via a parental
      questionnaire. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)
      were determined by enzyme-linked immunosorbent assay. C-reactive protein (CRP)
      was determined by solid-phase chemiluminescent immunometric assay. RESULTS:
      Nonadjusted and adjusted multivariate correlation analyses confirmed a strong
      association ( p < .001, 95% confidence interval) between the three markers of
      inflammation and exclusive breastfeeding duration. No significant differences
      were observed for IL-6, TNF-alpha, and CRP serum concentrations among normal
      weight, overweight, and obese adolescents, except for IL-6 between normal weight
      and obese subjects. Likewise, no significant association was found between these
      markers of inflammation and body mass index (BMI) z-score. CONCLUSIONS: We found
      a possible association between inflammatory markers and exclusive breastfeeding
      duration in adolescents, regardless of their BMI. This finding suggests that
      increased body weight or obesity might not mediate the association between
      breastfeeding and inflammation. These results contribute to the understanding of
      the relationship between breastfeeding and inflammatory markers in adolescents.

PMID- 28427274
TI  - First principle-based models in plant suspension cell cultures: a review.
AB  - In this work, the development and application of published models for describing
      the behavior of plant cell cultures is reviewed. The structure of each type of
      model is analyzed and the new tendencies for the modeling of biotechnological
      processes that can be applied in plant cell cultures are presented. This review
      is a tool for clarifying the main features that characterize each type of model
      in the field of plant cell cultures and can be used as a support on the selection
      of the more suitable model type, taking into account the purpose of specific
      research.

PMID- 28427275
TI  - Chronic subdural haematomas in the elderly - is the jury out?

PMID- 28427276
TI  - Stereoselective total synthesis of (-)-(6S,2'R)-cryptocaryalactone.
AB  - We described a novel stereoselective total synthesis of (-)-(6S,2'R)
      cryptocaryalactone, a natural product containing syn/anti-6,8-diol/5,6-dihydro-2H
      pyran-2-one unit. The approach, which characterised a highly diastereoselective
      chelation-controlled Mukaiyama aldol reaction of a benzyl-protected aldehyde and
      a Yamaguchi lactonisation of a delta-hydroxy-trans-alpha,beta-unsaturated
      carboxylic acid, is an alternative synthetic strategy towards
      cryptocaryalactones.

PMID- 28427277
TI  - Biological activity and LC-MS/MS profiling of extracts from the Australian
      medicinal plant Acacia ligulata (Fabaceae).
AB  - Acacia ligulata A.Cunn. ex Benth. (Fabaceae: Mimosoideae) is a native Australian
      plant used traditionally by Australian Aboriginal groups. This study was
      undertaken to investigate the bioactivity of A. ligulata extracts and to evaluate
      their chemical composition. Potential antibacterial, cytotoxic and enzyme
      inhibitory effects relevant to traditional medicinal and food uses of the species
      were examined and LC-MS/MS was performed to investigate the chemical composition.
      Antibacterial activity was observed for bark and leaf extracts with an MIC for
      the bark extract of 62.5 MUg/mL against Streptococcus pyogenes. Pod extracts
      showed cytotoxic effects against cancer cells, with the highest activity against
      melanoma SK-MEL28 cells with IC50 values between 40.8 and 80.6 MUg/mL. Further,
      the leaf and pod extracts also inhibited alpha-amylase EC-3.2.1.1 and alpha
      glucosidase EC-3.2.1.20 with IC50 values between 9.7-34.8 and 12.6-64.3 MUg/mL,
      respectively. The LC-MS/MS profiling indicated that several different saponins
      were present in the active extracts.

PMID- 28427278
TI  - Open-access publishing, a double-edged blade.

PMID- 28427279
TI  - Does headache research need more or less journals: Cephalalgia and Open Access.

PMID- 28427280
TI  - Progress in terpene synthesis strategies through engineering of Saccharomyces
      cerevisiae.
AB  - Terpenes are natural products with a remarkable diversity in their chemical
      structures and they hold a significant market share commercially owing to their
      distinct applications. These potential molecules are usually derived from
      terrestrial plants, marine and microbial sources. In vitro production of terpenes
      using plant tissue culture and plant metabolic engineering, although receiving
      some success, the complexity in downstream processing because of the interference
      of phenolics and product commercialization due to regulations that are
      significant concerns. Industrial workhorses' viz., Escherichia coli and
      Saccharomyces cerevisiae have become microorganisms to produce non-native
      terpenes in order to address critical issues such as demand-supply imbalance,
      sustainability and commercial viability. S. cerevisiae enjoys several advantages
      for synthesizing non-native terpenes with the most significant being the
      compatibility for expressing cytochrome P450 enzymes from plant origin. Moreover,
      achievement of high titers such as 40 g/l of amorphadiene, a sesquiterpene,
      boosts commercial interest and encourages the researchers to envisage both
      molecular and process strategies for developing yeast cell factories to produce
      these compounds. This review contains a brief consideration of existing
      strategies to engineer S. cerevisiae toward the synthesis of terpene molecules.
      Some of the common targets for synthesis of terpenes in S. cerevisiae are as
      follows: overexpression of tHMG1, ERG20, upc2-1 in case of all classes of
      terpenes; repression of ERG9 by replacement of the native promoter with a
      repressive methionine promoter in case of mono-, di- and sesquiterpenes;
      overexpression of BTS1 in case of di- and tetraterpenes. Site-directed
      mutagenesis such as Upc2p (G888A) in case of all classes of terpenes, ERG20p
      (K197G) in case of monoterpenes, HMG2p (K6R) in case of mono-, di- and
      sesquiterpenes could be some generic targets. Efforts are made to consolidate
      various studies (including patents) on this subject to understand the
      similarities, to identify novel strategies and to contemplate potential
      possibilities to build a robust yeast cell factory for terpene or terpenoid
      production. Emphasis is not restricted to metabolic engineering strategies
      pertaining to sterol and mevalonate pathway, but also other holistic approaches
      for elsewhere exploitation in the S. cerevisiae genome are discussed. This review
      also focuses on process considerations and challenges during the mass production
      of these potential compounds from the engineered strain for commercial
      exploitation.

PMID- 28427281
TI  - The Servier oncology pipeline in 2017.
AB  - Cancer is a complex, multifactorial disease that for years has been the focus of
      intensive research efforts to explore both the molecular and biological
      mechanisms involved and the development of novel agents to target these pathways.
      Servier is an independent French pharmaceutical company with a focus on oncology.
      Currently, Servier's commercial portfolio includes agents used to treat non
      Hodgkin's lymphoma and metastatic colorectal cancer; Servier's oncology pipeline
      involves agents for the treatment of both solid and hematological tumors. The
      main areas of future research focus on the development of therapeutics targeting
      apoptosis or the active immune components involved in tumour
      development/maintenance. Servier intends to continue its focus on cutting-edge
      oncology innovation by collaborating with both industry and academia, and
      maintaining its strong patient-centered approach.

PMID- 28427282
TI  - Biofouling in photobioreactors for marine microalgae.
AB  - The economic and/or energetic feasibility of processes based on using microalgae
      biomass requires an efficient cultivation system. In photobioreactors (PBRs), the
      adhesion of microalgae to the transparent PBR surfaces leads to biofouling and
      reduces the solar radiation penetrating the PBR. Light reduction within the PBR
      decreases biomass productivity and, therefore, the photosynthetic efficiency of
      the cultivation system. Additionally, PBR biofouling leads to a series of further
      undesirable events including changes in cell pigmentation, culture degradation,
      and contamination by invasive microorganisms; all of which can result in the
      cultivation process having to be stopped. Designing PBR surfaces with proper
      materials, functional groups or surface coatings, to prevent microalgal adhesion
      is essential for solving the biofouling problem. Such a significant advance in
      microalgal biotechnology would enable extended operational periods at high
      productivity and reduce maintenance costs. In this paper, we review the few
      systematic studies performed so far and applied the existing thermodynamic and
      colloidal theories for microbial biofouling formation in order to understand
      microalgal adhesion on PBR surfaces and the microalgae-microalgae cell
      interactions. Their relationship to the physicochemical properties of the solid
      PBR surface, the microalgae cell surfaces, and the ionic strength of the culture
      medium is discussed. The suitability and the applicability of such theories are
      reviewed. To this end, an example of biofouling formation on a commercial glass
      surface is presented for the marine microalgae Nannochloropsis gaditana. It
      highlights the adhesion dynamics and the inaccuracies of the process and the need
      for further refinement of previous theories so as to apply them to flowing
      systems, such as is the case for PBRs used to culture microalgae.

PMID- 28427283
TI  - Break induced replication in eukaryotes: mechanisms, functions, and consequences.
AB  - Break-induced replication (BIR) is an important pathway specializing in repair of
      one-ended double-strand DNA breaks (DSBs). This type of DSB break typically
      arises at collapsed replication forks or at eroded telomeres. BIR initiates by
      invasion of a broken DNA end into a homologous template followed by initiation of
      DNA synthesis that can proceed for hundreds of kilobases. This synthesis is
      drastically different from S-phase replication in that instead of a replication
      fork, BIR proceeds via a migrating bubble and is associated with conservative
      inheritance of newly synthesized DNA. This unusual mode of DNA replication is
      responsible for frequent genetic instabilities associated with BIR, including
      hyper-mutagenesis, which can lead to the formation of mutation clusters,
      extensive loss of heterozygosity, chromosomal translocations, copy-number
      variations and complex genomic rearrangements. In addition to budding yeast
      experimental systems that were initially employed to investigate eukaryotic BIR,
      recent studies in different organisms including humans, have provided multiple
      examples of BIR initiated within different cellular contexts, including collapsed
      replication fork and telomere maintenance in the absence of telomerase. In
      addition, significant progress has been made towards understanding microhomology
      mediated BIR (MMBIR) that can promote complex chromosomal rearrangements,
      including those associated with cancer and those leading to a number of
      neurological disorders in humans.

PMID- 28427284
TI  - Delivering tertiary centre specialty care to ALS patients via telemedicine: a
      retrospective cohort analysis.
AB  - OBJECTIVE: This study was undertaken to determine if ALS patients evaluated via
      telemedicine received the same quality of care as patients evaluated by
      traditional face-to-face encounters. METHODS: A retrospective cohort study design
      was used. Participants were patients diagnosed with ALS that received
      multidisciplinary care at the tertiary Cleveland VA ALS Centre between 1 March
      2008- and 31 anuary 2015. Participants were not randomised, but chose
      telemedicine based on preference, disability level or distance from the clinic.
      Telemedicine in this study consisted of a video conferencing platform enabling
      remote rather than face-to-face encounters with participants. RESULTS: There was
      no significant association between receiving quality ALS care and the mode of
      care. There was a trend for telemedicine patients to utilise home health care
      less often than those that received clinic care (AOR 0.50; 95% CI 0.16-1.59).
      There was no significant difference in survival time between the two groups (log
      rank test chi2 = 3.62, df = 1, p = 0.05). Patients receiving telemedicine had a
      higher probability of remaining stable or having <30% decrease in ALSFRS-R over
      time (log-rank test chi2 = 4.46, df = 1, p = 0.03). There was a significantly
      lower risk of disease progression for patients receiving telemedicine (HR = 0.39,
      95% CI = 0.16-0.93). CONCLUSIONS: Patients managed by telemedicine received the
      same quality of care and had similar outcomes to those patients seen via
      traditional face-to-face encounters. Telemedicine is an effective platform for
      delivering high quality tertiary ALS care.

PMID- 28427286
TI  - Incomes and Outcomes: Social Security Disability Benefits in First-Episode
      Psychosis.
AB  - OBJECTIVE: Social Security Administration (SSA) disability benefits are an
      important source of income for people with psychoses and confer eligibility for
      health insurance. The authors examined the impact of coordinated specialty care
      on receipt of such benefits in first-episode psychosis, along with the correlates
      and consequences of receiving them. METHOD: The Recovery After an Initial
      Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study, a 34-site
      cluster-randomized trial, compared NAVIGATE, a coordinated specialty care
      program, to usual community care over 2 years. Receipt of SSA benefits and
      clinical outcomes were assessed at program entry and every 6 months for 2 years.
      Piecewise regression analysis was used to identify relative change in outcome
      trajectories after receipt of disability benefits. RESULTS: Among 399 RAISE-ETP
      participants, 36 (9%) were receiving SSA disability benefits at baseline; of the
      remainder, 124 (34.1%) obtained benefits during the 2-year study period. The
      NAVIGATE intervention improved quality of life, symptoms, and employment but did
      not significantly reduce the likelihood of receiving SSA disability benefits.
      Obtaining benefits was predicted by more severe psychotic symptoms and greater
      dysfunction and was followed by increased total income but fewer days of
      employment, reduced motivation (e.g., sense of purpose, greater anhedonia), and
      fewer days of intoxication. CONCLUSIONS: A 2-year coordinated specialty care
      intervention did not reduce receipt of SSA disability benefits. There were some
      advantages for those who obtained SSA disability benefits over the 2-year
      treatment period, but there were also some unintended adverse consequences.
      Providing income supports without impeding recovery remains an important policy
      challenge.

PMID- 28427287
TI  - Downstream protein separation by surfactant precipitation: a review.
AB  - In a conventional protein downstream processing (DSP) scheme, chromatography is
      the single most expensive step. Despite being highly effective, it often has a
      low process throughput due to its semibatch nature, sometimes with
      nonreproducible results and relatively complex process development. Hence, more
      work is required to develop alternative purification methods that are more cost
      effective, but exhibiting nearly comparable performance. In recent years,
      surfactant precipitation has been heralded as a promising new method for primary
      protein recovery that meets these criteria and is a simple and cost-effective
      method that purifies and concentrates. The method requires the direct addition of
      a surfactant to a complex solution (e.g. a fermentation broth) containing the
      protein of interest, where the final surfactant concentration is maintained below
      its critical micelle concentration (CMC) in order to allow for electrostatic and
      hydrophobic interactions between the surfactant and the target protein. An
      insoluble (hydrophobic) protein-surfactant complex is formed and backextraction
      of the target protein from the precipitate into a new aqueous phase is then
      carried out using either solvent extraction, or addition of a counter-ionic
      surfactant. Importantly, as highlighted by past researchers, the recovered
      proteins maintain their activity and structural integrity, as determined by
      circular dichroism (CD). In this review, various aspects of surfactant
      precipitation with respect to its general methodology and process mechanism,
      system parameters influencing performance, protein recovery, process selectivity
      and process advantages will be highlighted. Moreover, comparisons will be made to
      reverse micellar extraction, and the current drawbacks/challenges of surfactant
      precipitation will also be discussed. Finally, promising directions of future
      work with this separation technique will be highlighted.

PMID- 28427285
TI  - Premenstrual Dysphoric Disorder Symptoms Following Ovarian Suppression: Triggered
      by Change in Ovarian Steroid Levels But Not Continuous Stable Levels.
AB  - OBJECTIVE: Premenstrual dysphoric disorder (PMDD) symptoms are eliminated by
      ovarian suppression and stimulated by administration of ovarian steroids, yet
      they appear with ovarian steroid levels indistinguishable from those in women
      without PMDD. Thus, symptoms could be precipitated either by an acute change in
      ovarian steroid levels or by stable levels above a critical threshold playing a
      permissive role in expression of an underlying infradian affective "pacemaker."
      The authors attempted to determine which condition triggers PMDD symptoms.
      METHOD: The study included 22 women with PMDD, ages 30 to 50 years. Twelve women
      who experienced symptom remission after 2-3 months of GnRH agonist-induced
      ovarian suppression (leuprolide) then received 1 month of single-blind
      (participant only) placebo and then 3 months of continuous combined
      estradiol/progesterone. Primary outcome measures were the Rating for Premenstrual
      Tension observer and self-ratings completed every 2 weeks during clinic visits.
      Multivariate repeated-measure ANOVA for mixed models was employed. RESULTS: Both
      self- and observer-rated scores on the Rating for Premenstrual Tension were
      significantly increased (more symptomatic) during the first month of combined
      estradiol/progesterone compared with the last month of leuprolide alone, the
      placebo month, and the second and third months of estradiol/progesterone. There
      were no significant differences in symptom severity between the last month of
      leuprolide alone, placebo month, or second and third months of
      estradiol/progesterone. Finally, the Rating for Premenstrual Tension scores in
      the second and third estradiol/progesterone months did not significantly differ.
      CONCLUSIONS: The findings demonstrate that the change in estradiol/progesterone
      levels from low to high, and not the steady-state level, was associated with
      onset of PMDD symptoms. Therapeutic efforts to modulate the change in steroid
      levels proximate to ovulation merit further study.

PMID- 28427288
TI  - Cigarette smokers develop altered erythrocyte membrane composition: an
      investigation unmasking the role of membrane bound integral protein GLUT 1.
AB  - Erythrocytes in cigarette smokers are prone to oxidative damage. Here, we sought
      to elucidate the facts behind modifications and possible defense system developed
      in erythrocyte of cigarette smokers. We observed significant increase in
      stomatocytes and spherocytes, and osmotic fragility of erythrocyte, along with
      reduced level of protein thiol and increased fluorescence anisotropy in isolated
      membrane. Denaturing gel electrophoresis indicated alterations in band 3, band
      4.2 and band 4.5. Among those, Glut 1 (i.e. band 4.5), which transports glucose
      (insulin independent) and dehydroascorbate (DHA), was selectively chosen for its
      long history in reducing reactive oxygen species (ROS). The increased Glut 1
      level in smokers was confirmed by immunoblotting and immunocytochemistry.
      Furthermore, smokers showed significantly higher glucose uptake in whole blood.
      The intracellular (Ic) ROS (as indicated by 2',7'-dichlorofluorescin) was
      significantly higher in smokers as evidenced by flow cytometric assay. Glucose
      and DHA alone or together significantly reduced IcROS at higher rate in smokers.
      However, in presence of Glut 1 specific blocker, phloretin, neither glucose nor
      DHA could reduce IcROS in both non-smokers and smokers. This confirms that Glut 1
      by transporting glucose or DHA attenuates IcROS. Therefore, we conclude that
      erythrocytes, although altered morphologically, also develop a defense system by
      upregulating Glut 1 to combat with enhanced Ic oxidative insult in cigarette
      smokers.

PMID- 28427289
TI  - Biomarkers for diagnosis of neonatal sepsis: a literature review.
AB  - Sepsis is an important cause of mortality and morbidity in neonatal populations.
      There has been constant search of an ideal sepsis biomarker that have high
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV), so that both the diagnosis and exclusion of neonatal sepsis can be
      made at the earliest possible and appropriate antibiotics can be started to
      neonate. Ideal sepsis biomarker will help in guiding us when not to start
      antibiotics in case of suspect sepsis and total duration of antibiotics course in
      case of proven sepsis. There are numerous sepsis biomarkers that have been
      evaluated for early detection of neonatal sepsis but till date there is no single
      ideal biomarker that fulfills all essential criteria's for being an ideal
      biomarker. The most commonly used biomarkers are C-reactive protein (CRP) and
      procalcitonin (PCT), but both have shown varied sensitivity, specificity, PPV and
      NPV in different studies. We conducted literature search for various neonatal
      sepsis biomarkers and this review article will cover briefly all the markers with
      current available evidence.

PMID- 28427290
TI  - A Real-Time Method for Decoding the Neural Drive to Muscles Using Single-Channel
      Intra-Muscular EMG Recordings.
AB  - The neural command from motor neurons to muscles - sometimes referred to as the
      neural drive to muscle - can be identified by decomposition of electromyographic
      (EMG) signals. This approach can be used for inferring the voluntary commands in
      neural interfaces in patients with limb amputations. This paper proposes for the
      first time an innovative method for fully automatic and real-time intramuscular
      EMG (iEMG) decomposition. The method is based on online single-pass density-based
      clustering and adaptive classification of bivariate features, using the concept
      of potential measure. No attempt was made to resolve superimposed motor unit
      action potentials. The proposed algorithm was validated on sets of simulated and
      experimental iEMG signals. Signals were recorded from the biceps femoris long
      head, vastus medialis and lateralis and tibialis anterior muscles during low-to
      moderate isometric constant-force and linearly-varying force contractions. The
      average number of missed, duplicated and erroneous clusters for the examined
      signals was [Formula: see text], [Formula: see text], and [Formula: see text],
      respectively. The average decomposition accuracy (defined similar to signal
      detection theory but without using True Negatives in the denominator) and
      coefficient of determination (variance accounted for) for the cumulative
      discharge rate estimation were [Formula: see text], and [Formula: see text],
      respectively. The time cost for processing each 200[Formula: see text]ms iEMG
      interval was [Formula: see text] (21-97)[Formula: see text]ms. However,
      computational time generally increases over time as a function of frames/signal
      epochs. Meanwhile, the incremental accuracy defined as the accuracy of real-time
      analysis of each signal epoch, was [Formula: see text]% for epochs recorded after
      initial one second. The proposed algorithm is thus a promising new tool for
      neural decoding in the next-generation of prosthetic control.

PMID- 28427291
TI  - Antioxidant therapy for management of oxidative stress induced hypertension.
AB  - Hypertension is considered as the most common risk factor for cardiovascular
      diseases, also is regarded as a leading cause of the mortality and morbidity
      worldwide. The mechanisms underlying the pathological process of hypertension are
      not completely explained. However, there is growing evidence that increased
      oxidative stress plays an important role in the pathophysiology of hypertension.
      Several preclinical studies and clinical trials have indicated that antioxidant
      therapy is important for management of hypertension, using antioxidants compounds
      such as alpha tocopherol (Vit E) and ascorbic acid (Vit C), polyphenols with
      others and some antihypertensive drugs that are now in clinical use (e.g. ACEIs,
      ARBs, novel B-blockers, dihydropyridine CCBs) which have antioxidative
      pleiotropic effects. The purpose of this review is to highlight the importance of
      antioxidant therapy for management of oxidative stress induced hypertension.
      Furthermore, we review the current knowledge in the oxidative stress and its
      significance in hypertension.

PMID- 28427292
TI  - Chemical analyses and in vitro and in vivo toxicity of fruit methanol extract of
      Sechium edule var. nigrum spinosum.
AB  - CONTEXT: Sechium edule (Jacq.) Sw. (Cucurbitaceae) is used in ethnomedicine, but
      the diversity of the varietal groups of this species has not often been
      considered. This is important because we previously reported that different
      variety of species exhibit different activities across different tumor cell
      lines. OBJECTIVE: This study investigates the chemical composition and biological
      activities of extracts obtained from S. edule var. nigrum spinosum. MATERIALS AND
      METHODS: The leukemia P388 cell line and mononuclear bone marrow cells (MNCBMs)
      were treated with the extract at a concentration ranging from 40 to 2370 MUg/mL
      for cytotoxicity and viability assays. CD-1 mice were treated with 8-5000 mg/kg
      extract and monitored every hour for the first 24 h and subsequently for seven
      days for signs of toxicity (LD50). In addition, the chromatographic profile of
      the extract was determined by HPLC. RESULTS: The extract inhibits the
      proliferation of both P388 cells and MNCBMs, with IC50 values of 927 and 1911
      MUg/mL, respectively, but reduced the viability and induced the apoptosis of only
      leukemia cells. The LD50 was higher than 5000 mg/kg, and this concentration did
      not alter the blood chemistry or cell count but doubled the mitotic index in the
      bone marrow. The HPLC showed the presence of cucurbitacins, phloridzin,
      naringenin, phloretin, apigenin, and gallic, chlorogenic, vanillic, p
      hydroxybenzoic, caffeic, and p-coumaric acids. DISCUSSION AND CONCLUSION: Sechium
      edule var. nigrum spinosum contains bioactive compounds that explain the
      antiproliferative and nutraceutical activities, and its lack of physiological
      side effects constitutes an added value to a widely consumed vegetable.

PMID- 28427293
TI  - Beneficial effects of tyrosol on altered glycoprotein components in
      streptozotocin-induced diabetic rats.
AB  - CONTEXT: Olive oil is the major source of tyrosol which is a natural phenolic
      antioxidant. Olive oil constitutes a major component of the Mediterranean diet
      that is linked to a reduced incidence of chronic diseases. OBJECTIVE: This study
      evaluates the effects of tyrosol on altered glycoprotein components in
      streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Diabetes mellitus
      was induced in male Wistar rats by streptozotocin (40 mg/kg body weight). These
      rats were administered tyrosol (20 mg/kg body weight) and glibenclamide (600
      MUg/kg body weight) orally daily for 45 days. Plasma glucose, plasma insulin,
      glycoprotein components such as hexose, hexosamine, sialic acid and fucose in the
      plasma, liver and kidney, and histopathogy of tissues were analyzed. RESULTS:
      Diabetic rats revealed significant (p < 0.05) increase in the levels of glucose,
      hexose, hexosamine, sialic acid and fucose (277.17, 152.45, 100.43, 79.69 and
      49.29 mg/dL) in the plasma; decrease in the levels of palsma insulin (6.12
      MUU/mL) and sialic acid (4.36 and 5.03 mg/g) in the liver and kidney; significant
      (p < 0.05) increase in hexose (49.33 and 46.82 mg/g), hexosamine (22.68 and 33.20
      mg/g) and fucose (31.63 and 32.44 mg/g) in the liver and kidney. Further,
      periodic acid-Schiff staining of tissues revealed positive-stain accumulation in
      diabetic rats. Tyrosol treatment showed significant (p < 0.05) effects on all the
      biochemical parameters and histopathology studied in streptozotocin- nduced
      diabetic rats. Also, the in vitro study revealed the antioxidant effect of
      tyrosol. DISCUSSION AND CONCLUSIONS: Thus, tyrosol protects streptozotocin
      induced diabetic rats from the altered glycoprotein components. Further, this
      study can be extrapolated to humans.

PMID- 28427294
TI  - Increased phagocytic NADPH oxidase activity associates with coronary artery
      calcification in asymptomatic men.
AB  - Vascular calcification is a common feature in atherosclerosis and associates with
      cardiovascular events. Oxidative stress may be involved in the pathogenesis of
      vascular calcification. Previous studies have shown that the phagocytic NADPH
      oxidase is associated with atherosclerosis. The objective of the present study
      was to investigate the association between phagocytic NADPH oxidase-mediated
      superoxide production and coronary artery calcium (CAC). NADPH oxidase-mediated
      superoxide production was determined by chemiluminescence and CAC by computed
      tomography in 159 asymptomatic men free of overt clinical atherosclerosis.
      Multivariate linear regression analyses were used to assess the relationship
      between CAC and NADPH oxidase-mediated superoxide production. Compared with
      individuals in the lowest score of CAC (= 0 Agatston units), those in the upper
      score (>400 Agatston units) showed higher superoxide production (p < 0.05). In
      correlation analysis, superoxide production positively (p < 0.01) correlated with
      CAC, which in multivariate analysis remained significant after adjusting for age,
      HDL-cholesterol, triglycerides, body mass index, smoking, arterial hypertension
      and diabetes mellitus. In conclusion, in a population of men without clinically
      overt atherosclerotic disease, increased NADPH oxidase-mediated superoxide
      production associated with enhanced CAC. Albeit descriptive, these findings
      suggest a potential involvement of phagocytic NADPH oxidase-mediated oxidative
      stress in CAC.

PMID- 28427295
TI  - Development of visuo-haptic transfer for object recognition in typical preschool
      and school-aged children.
AB  - Object recognition is a long and complex adaptive process and its full maturation
      requires combination of many different sensory experiences as well as cognitive
      abilities to manipulate previous experiences in order to develop new percepts and
      subsequently to learn from the environment. It is well recognized that the
      transfer of visual and haptic information facilitates object recognition in
      adults, but less is known about development of this ability. In this study, we
      explored the developmental course of object recognition capacity in children
      using unimodal visual information, unimodal haptic information, and visuo-haptic
      information transfer in children from 4 years to 10 years and 11 months of age.
      Participants were tested through a clinical protocol, involving visual
      exploration of black-and-white photographs of common objects, haptic exploration
      of real objects, and visuo-haptic transfer of these two types of information.
      Results show an age-dependent development of object recognition abilities for
      visual, haptic, and visuo-haptic modalities. A significant effect of time on
      development of unimodal and crossmodal recognition skills was found. Moreover,
      our data suggest that multisensory processes for common object recognition are
      active at 4 years of age. They facilitate recognition of common objects, and,
      although not fully mature, are significant in adaptive behavior from the first
      years of age. The study of typical development of visuo-haptic processes in
      childhood is a starting point for future studies regarding object recognition in
      impaired populations.

PMID- 28427296
TI  - Predictors of response to therapy with omalizumab in patients with severe
      allergic asthma - a real life study.
AB  - OBJECTIVES: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE
      antibody, used for the treatment of severe refractory allergic asthma. However,
      not all patients with IgE levels within the limits of administration, respond to
      treatment. The aim of the present study, was to determine clinical and
      inflammatory characteristics that could predict response to omalizumab. METHODS:
      We studied retrospectively patients treated with omalizumab as per GINA
      guidelines in one asthma tertiary referral center. Demographic and functional
      characteristics, level of asthma control, fractional exhaled nitric oxide, blood
      and eosinophils and IgE level, induced sputum cell count, eosinophil cationic
      protein and Interleukin-13 in sputum supernatant were recorded. All measurements
      were performed before starting treatment with omalizumab. Response to treatment
      was evaluated according to the physician's global evaluation of treatment
      effectiveness. Patients were characterized as early responders when improvement
      was achieved within 16 weeks and as late responders when improvement was achieved
      between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks
      of therapy were considered as non-responders. RESULTS: Forty-one patients treated
      with omalizumab were included in the study. 28 (68.3%) patients were
      characterized as responders while 13 patients (31.7%) were considered as non
      responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were
      late responders. Responders were characterized by lower baseline FEV1 and
      FEV1/FVC and higher IL-13 levels in induced sputum supernatant compared to non
      responders. Late responders had higher serum IgE levels, shorter disease duration
      and higher number of blood eosinophils. Finally, using ROC curve analysis, the
      best predictors of response to omalizumab were FEV1 (AUC = 0.718) and IL-13 in
      sputum supernatant (AUC = 0.709). CONCLUSION: Lower baseline FEV1 and higher IL
      13 levels in induced sputum supernatant were predictors of response to
      omalizumab. Patients with higher baseline serum IgE levels, shorter disease
      duration and higher blood eosinophils may experience a late response and might
      benefit from a more prolonged treatment before being characterized as non
      responders.

PMID- 28427297
TI  - The effect of moisture content within multilayer protective clothing on
      protection from radiation and steam.
AB  - The moisture from skin sweat and atmospheric water affects the thermal protective
      performance provided by multilayer protective clothing. Four levels of moisture
      content were selected to evaluate the impact of moisture on thermal protection
      under dry (thermal radiation) and wet (thermal radiation and low-pressure steam)
      heat exposure. Also, the role of moisture and its relationship with exposure time
      were analyzed based on skin heat flux and Henriques integral value. The addition
      of moisture to a fabric system was found to result in differences in second
      degree and third-degree skin burn times. When moisture is added to a fabric
      system, it both acts as a thermal conductor to present a negative effect and
      provides a positive effect owing to thermal storage of water and evaporative heat
      loss. The positive or negative effects of moisture are mainly dependent on the
      thermal exposure time, the moisture content and the presence of hot steam.

PMID- 28427298
TI  - Recent advances in pediatric gastrointestinal endoscopy: an overview.
AB  - INTRODUCTION: Pediatric gastrointestinal endoscopy has become a fundamental
      component of health care for infants and children. New imaging technologies and
      creative extraluminal applications have brought exciting and clinically important
      benefits to pediatric gastrointestinal endoscopy. Areas covered: The impact of
      different new technologies in pediatric endoscopy and focused on improvements in
      mucosa visualization and the application of new noninvasive tools and procedures
      to avoid biopsies or surgery are reviewed. Expert commentary: Enhancement in
      mucosal visualization and reduction of anesthesia and biopsies are the main goals
      that guide the endoscopy development in pediatrics. The advent of newer imaging
      modalities has allowed clinicians to characterize and evaluate subtle mucosal
      lesions better, while advancements in current endoscopes have created the
      opportunity to monitor chronic conditions noninvasively. Continued expansion of
      these modalities seems certain, with increased utilization in pediatric
      gastroenterology.

PMID- 28427299
TI  - Effects of low-frequency repetitive transcranial magnetic stimulation on upper
      extremity motor recovery and functional outcomes in chronic stroke patients: A
      randomized controlled trial.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) was suggested as
      a preconditioning method that would increase brain plasticity and that it would
      be optimal to combine rTMS with intensive rehabilitation. OBJECTIVE: To assess
      the efficacy of inhibitory rTMS on upper extremity motor recovery and functional
      outcomes in chronic ischemic stroke patients. METHODS: In this randomized
      controlled trial, experimental group received low-frequency (LF) rTMS to the
      primary motor cortex of the unaffected side + physical therapy (PT), and control
      group received PT. RESULTS: No statistically significant difference was found in
      baseline demographical and clinical characteristics of the subjects including
      stroke severity or severity of paralysis prior to intervention. There were
      statistically significant improvements in all clinical outcome measures except
      for the Brunnstrom Recovery Stages. Fugl-Meyer Assessment, Box and Block test,
      motor and total scores of Functional Independence Measurement (FIM), and
      Functional Ambulation Scale (FAS) scores were significantly increased in both
      groups, however, these changes were significantly greater in the rTMS group
      except for FAS score. FIM cognitive scores and standardized mini-mental test
      scores were significantly increased and distal and hand Modified Ashworth Scale
      scores were significantly decreased only in the rTMS group (p < .05).
      CONCLUSIONS: LF-rTMS can safely facilitate upper extremity motor recovery in
      patients with chronic ischemic stroke. TMS seems to be a promising treatment for
      motor, functional, and cognitive deficits in chronic stroke. Further studies with
      a larger number of patients with longer follow-up periods are needed to establish
      its effectiveness in stroke rehabilitation.

PMID- 28427300
TI  - Object decision test (BORB): normative data for the adult Quebec population and
      performance in Alzheimer's disease and the semantic variant of primary
      progressive aphasia.
AB  - Object decision (OD) test is one subtest of the Birmingham Object Recognition
      Battery (BORB). It is useful for differential diagnosis among several
      neurodegenerative diseases. However, normative data provided with this battery
      count on very few subjects and do not control for the effect of age, which limits
      interpretability. The purpose of Study 1 was to provide normative data for the OD
      test of the BORB (version A-hard). The objectives of Study 2 were to establish
      the diagnostic validity of this task and predictive validity of the normative
      data in the case of the semantic variant of primary progressive aphasia (svPPA)
      and Alzheimer's disease (AD).Based on multiple linear regressions, equations to
      calculate Z-scores corrected for age were provided for 130 participants aged from
      47 to 89 years. Performance of 20 healthy participants was compared to that of 14
      individuals with svPPA and 18 with AD. After controlling for confounders,
      participants with svPPA had a lower total score than controls and AD
      participants. AD participants had a poorer performance than controls only when
      chimeric objects were considered. Among those with a deficit on the total score
      of the test, 94% (17/18, including 12 with svPPA) were correctly identified as
      having a pathological condition (svPPA or AD). This test could help refine
      differential diagnosis between svPPA and AD patients, especially before the
      deficits of episodic memory show up.

PMID- 28427301
TI  - Corneal endothelial changes in long-term cannabinoid users.
AB  - PURPOSE: The aim of this study was at evaluating the effects of long-term
      cannabis use on the corneal endothelial cells with the specular microscopy.
      METHODS: The study enrolled 28 eyes of 28 patients diagnosed with cannabinoid use
      disorder. The cannabinoid group was selected among patients who had been using
      the substance for three days or more per week over the past one year. Thirty-two
      eyes of 32 age- and sex-matched healthy individuals enrolled as control group in
      the study. Corneal endothelial cell density (CD), coefficient of variation (CV)
      and hexagonal cell ratio (HEX) values were analyzed by specular microscopy.
      RESULTS: The mean CD was 2900 +/- 211 cells/mm2 in the cannabinoid group and 3097
      +/- 214 cells/mm2 in the control group (p < 0.01). There was a significant
      decrease in cannabinoid group. The mean CV was 29 +/- 7 and 27 +/- 4 in the
      cannabinoid and control groups, respectively (p > 0.05). No significant
      difference was present between the cannabinoid and the control groups in terms of
      mean CV value. The mean HEX was 52 +/- 5% in the cannabinoid group and 53 +/- 10%
      in the control group (p > 0.05). There was not a significant difference between
      the cannabinoid and the control groups in terms of mean HEX value. CONCLUSION: A
      significant decrease in CD was found in cannabinoid users compared the control
      group.

PMID- 28427302
TI  - Increasing Influenza Immunization Rates Among Retail Employees: An Evidence-Based
      Approach.
AB  - Influenza has a significant impact on the health of Americans and the U.S.
      economy. Annual influenza immunization can decrease the burden of influenza
      related illnesses for both employees and employers. This project evaluated a
      nurse practitioner-led intervention to increase influenza immunization rates
      among retail employees from August through December of the 2015-2016 influenza
      season. The sample included employees from retail locations with on-site
      convenience care clinics staffed by nurse practitioners. This quality improvement
      project used a pre-post implementation evaluation design and compared influenza
      immunization rates of employees, before and after an intervention, at one
      worksite, and influenza immunization rates of employees, who did not receive the
      same intervention, at a comparison site. The intervention site employees were
      immunized at a higher rate than employees at the comparison site. Interventions,
      including health care professional-led education, program promotion, on-site
      access to and no-cost immunizations, choice of immunization delivery, and
      incentives, should be considered to increase immunization rates among employees.

PMID- 28427303
TI  - Values based practice: a framework for thinking with.
AB  - Values are those principles that govern behaviours, and values-based practice has
      been described as a theory and skills base for effective healthcare decision
      making where different (and hence potentially conflicting) values are in play.
      The emphasis is on good process rather than pre-set right outcomes, aiming to
      achieve balanced decision-making. In this article we will consider the utility of
      this model by looking at leadership development, a current area of much interest
      and investment in healthcare. Copeland points out that 'values based leadership
      behaviors are styles with a moral, authentic and ethical dimension', important
      qualities in healthcare decision-making.

PMID- 28427304
TI  - Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A
      Diabetes Educator/Expert Prescriber Team Approach.
AB  - Purpose The purpose of this article is to provide recommendations to the diabetes
      educator/expert prescriber team for the use of human regular U-500 insulin (U
      500R) in patients with severely insulin-resistant type 2 diabetes, including its
      initiation and titration, by utilizing dosing charts and teaching materials
      translated from a recent U-500R clinical trial. Conclusions Clinically relevant
      recommendations and teaching materials for the optimal use and management of U
      500R in clinical practice are provided based on the efficacy and safety results
      of and lessons learned from the U-500R clinical trial by Hood et al, current
      standards of practice, and the authors' clinical expertise. This trial was the
      first robustly powered, randomized, titration-to-target trial to compare twice
      daily and three-times-daily U-500R dosing regimens. Modifications were made to
      the initiation and titration dosing algorithms used in this trial to simplify
      dosing strategies for the clinical setting and align with current glycemic
      targets recommended by the American Diabetes Association. Leveraging the
      expertise, resources, and patient interactions of the diabetes educator who can
      provide diabetes self-management education and support in collaboration with the
      multidisciplinary diabetes team is strongly recommended to ensure patients
      treated with U-500R receive the timely and comprehensive care required to safely
      and effectively use this highly concentrated insulin.

PMID- 28427305
TI  - Neuromechanical adaptations during a robotic powered exoskeleton assisted walking
      session.
AB  - OBJECTIVE: To evaluate gait parameters and neuromuscular profiles of exoskeleton
      assisted walking under Max Assist condition during a single-session for; (i) able
      bodied (AB) individuals walking assisted with (EXO) and without (non-EXO) a
      powered exoskeleton, (ii) non-ambulatory SCI individuals walking assisted with a
      powered exoskeleton. DESIGN: Single-session. SETTING: Motion analysis laboratory.
      PARTICIPANTS: Four AB individuals and four individuals with SCI. INTERVENTIONS:
      Powered lower extremity exoskeleton. OUTCOME MEASURES: Temporal-spatial
      parameters, kinematics, walking velocity and electromyography data. RESULTS: AB
      individuals in exoskeleton showed greater stance time and a significant reduction
      in walking velocity (P < 0.05) compared to non-EXO walking. Interestingly, when
      the AB individuals voluntarily assisted the exoskeleton movements, they walked
      with an increased velocity and lowered stance time to resemble that of slow
      walking. For SCI individuals, mean percent stance time was higher and walking
      velocity was lower compared to all AB walking conditions (P < 0.05). There was
      muscle activation in several lower limb muscles for SCI group. For AB
      individuals, there were similarities among EXO and non-EXO walking conditions
      however there were differences in several lower limb EMGs for phasing of muscle
      activation. CONCLUSION: The data suggests that our AB individuals experienced
      reduction in walking velocity and muscle activation amplitudes while walking in
      the exoskeleton and moreover with voluntary control there is a greater temporal
      spatial response of the lower limbs. Also, there are neuromuscular phasic
      adaptions for both AB and SCI groups while walking in the exoskeleton that are
      inconsistent to non-EXO gait muscle activation.

PMID- 28427306
TI  - Prefrontal tDCS and sertraline in obsessive compulsive disorder: a case report
      and review of the literature.
AB  - Obsessive-compulsive (OC) disorder is a disabling disorder resulting in
      tremendous individual and social burden. It has a large overlap with depression
      and anxiety disorders and shows treatment resistance in a relevant proportion of
      patients. Since a couple of years, different noninvasive brain stimulation
      methods have been investigated to improve OC symptoms. The application of
      transcranial direct current stimulation (tDCS) has shown inconsistent results
      which can probably be attributed to a lack in randomized controlled trials with
      adequate sample size. Anodal stimulation of pre-supplementary motor areas has
      shown promising results, and there is also sparse data on orbitofrontal and
      prefrontal stimulation. Here, we provide the first report on a patient with
      treatment-refractory OC disorder treated with sertraline and an enhanced
      prefrontal tDCS protocol (twice per day, 10 days) with a classic left
      anodal/right cathodal montage, experiencing a 22% reduction of OC symptoms as
      well as reduction in depression (-10%) and anxiety symptoms (-21%). Due to
      multifactorial origin of OC disorder and the variety of brain circuits involved,
      there are probably multiple approaches for brain stimulation regarding site,
      polarity, and frequency to be assessed in future studies.

PMID- 28427307
TI  - Molecular dynamics, thermodynamic, and mutational binding studies for tumor
      specific LyP-1 in complex with p32.
AB  - Recent studies in tumor homing peptides have shown the specificity of LyP-1
      (CGNKRTRGC) to tumor lymphatics. In this present work, we evaluated the possible
      interactions between cyclic LyP-1 and its receptor, p32, with molecular dynamics
      and docking studies in order to lead the design of novel LyP-1 derivatives, which
      could bind to p32 more effectively and perform enhanced antitumor effect. The
      total binding enthalpy energies have been obtained by MM-PBSA thermodynamic
      computations and the favorability of p32.LyP-1 complex in water has been shown by
      explicit water MD computations. The last 30 ns of molecular dynamics trajectory
      have shown the strong interaction of LyP-1 with the inner surface chains of p32,
      especially with chains B and C. ALA-SCAN mutagenesis studies have indicated the
      considerable influence of Asn3, Lys4, Arg5, and Arg7 amino acid residues on the
      specific binding of LyP-1. Within the knowledge of the critical role of p32
      receptor in cancer cell metabolism, this study can lead to further developments
      in anticancer therapy by targeting p32 with LyP-1 derivatives as active targeting
      moiety. This data can also be applied for the development of new drug delivery
      systems in which LyP-1 can be used for its targeting and anticancer properties.

PMID- 28427308
TI  - Larger Stimuli Require Longer Processing Time for Perception.
AB  - The time it takes for a stimulus to reach awareness is often assessed by
      measuring reaction times (RTs) or by a temporal order judgement (TOJ) task in
      which perceived timing is compared against a reference stimulus. Dissociations of
      RT and TOJ have been reported earlier in which increases in stimulus intensity
      such as luminance intensity results in a decrease of RT, whereas perceived
      perceptual latency in a TOJ task is affected to a lesser degree. Here, we report
      that a simple manipulation of stimulus size has stronger effects on perceptual
      latency measured by TOJ than on motor latency measured by RT tasks. When
      participants were asked to respond to the appearance of a simple stimulus such as
      a luminance blob, the perceptual latency measured against a standard reference
      stimulus was up to 40 ms longer for a larger stimulus. In other words, the
      smaller stimulus was perceived to occur earlier than the larger one. RT on the
      other hand was hardly affected by size. The TOJ results were further replicated
      in a simultaneity judgement task, suggesting that the effects of size are not due
      to TOJ-specific response biases but more likely reflect an effect on perceived
      timing.

PMID- 28427312
TI  - Special Issue on 'Computational Modelling in Medicine': Guest editor
      introduction.

PMID- 28427311
TI  - Feasibility and Acceptability of a Clinic-based Mediterranean-style Diet
      Intervention to Reduce Cardiovascular Risk for Hispanic Americans With Type 2
      Diabetes.
AB  - Purpose The purpose of the study was to modify a previously tested Spanish
      language version of a Mediterranean (Med)-style dietary intervention so that the
      dietary recommendations align with the cultural and social needs of Hispanic
      Americans (HAs) with type 2 diabetes (T2D) and evaluate the modified
      intervention's feasibility and acceptability. Methods In phase I (formative),
      semi-structured interviews and focus groups were used to refine the intervention
      content and format for delivery to HAs with T2D receiving care at a large primary
      care practice. In phase II (clinical pilot), the 2-month intervention that
      promoted a Med-style dietary pattern was given to all participants via 2 face-to
      face counseling sessions and 2 telephone counseling sessions. Major outcomes were
      engagement with study activities and intervention acceptability; dietary behavior
      change at 2 months using the PREDIMED Med-diet score (range, 0-14, higher
      indicating better dietary pattern) is also reported. Results From clinic records,
      we identified 86 potentially eligible participants and enrolled 21. Baseline
      characteristics were: mean age = 52 years, 12 (57%) female, 15 (71%) from Mexico,
      mean years in the US = 19, low acculturation scores for all, and mean BMI = 33.7
      kg/m2. Engagement and acceptability were high, with 19 (90%) completing all
      intervention visits and follow-up measures, all of whom would recommend the
      program to others. Mean Med-diet score improved from 5.7 to 7.9 (difference =
      2.3; 95% CI, 1.0-3.5; P = .001). Conclusions Intervention engagement and
      acceptability were high, and there was improvement in self-reported dietary
      behaviors. This type of intervention should be evaluated in randomized trials
      enrolling HAs with diabetes.

PMID- 28427313
TI  - Sensitivity of a juvenile subject-specific musculoskeletal model of the ankle
      joint to the variability of operator-dependent input.
AB  - Subject-specific musculoskeletal modelling is especially useful in the study of
      juvenile and pathological subjects. However, such methodologies typically require
      a human operator to identify key landmarks from medical imaging data and are thus
      affected by unavoidable variability in the parameters defined and subsequent
      model predictions. The aim of this study was to thus quantify the inter- and
      intra-operator repeatability of a subject-specific modelling methodology
      developed for the analysis of subjects with juvenile idiopathic arthritis. Three
      operators each created subject-specific musculoskeletal foot and ankle models via
      palpation of bony landmarks, adjustment of geometrical muscle points and
      definition of joint coordinate systems. These models were then fused to a generic
      Arnold lower limb model for each of three modelled patients. The repeatability of
      each modelling operation was found to be comparable to those previously reported
      for the modelling of healthy, adult subjects. However, the inter-operator
      repeatability of muscle point definition was significantly greater than intra
      operator repeatability ( p < 0.05) and predicted ankle joint contact forces
      ranged by up to 24% and 10% of the peak force for the inter- and intra-operator
      analyses, respectively. Similarly, the maximum inter- and intra-operator
      variations in muscle force output were 64% and 23% of peak force, respectively.
      Our results suggest that subject-specific modelling is operator dependent at the
      foot and ankle, with the definition of muscle geometry the most significant
      source of output uncertainty. The development of automated procedures to prevent
      the misplacement of crucial muscle points should therefore be considered a
      particular priority for those developing subject-specific models.

PMID- 28427314
TI  - Capturing complexity in pulmonary system modelling.
AB  - Respiratory disease is a significant problem worldwide, and it is a problem with
      increasing prevalence. Pathology in the upper airways and lung is very difficult
      to diagnose and treat, as response to disease is often heterogeneous across
      patients. Computational models have long been used to help understand respiratory
      function, and these models have evolved alongside increases in the resolution of
      medical imaging and increased capability of functional imaging, advances in
      biological knowledge, mathematical techniques and computational power. The
      benefits of increasingly complex and realistic geometric and biophysical models
      of the respiratory system are that they are able to capture heterogeneity in
      patient response to disease and predict emergent function across spatial scales
      from the delicate alveolar structures to the whole organ level. However, with
      increasing complexity, models become harder to solve and in some cases harder to
      validate, which can reduce their impact clinically. Here, we review the evolution
      of complexity in computational models of the respiratory system, including
      successes in translation of models into the clinical arena. We also highlight
      major challenges in modelling the respiratory system, while making use of the
      evolving functional data that are available for model parameterisation and
      testing.

PMID- 28427315
TI  - Computational modeling of long-term effects of prophylactic vertebroplasty on
      bone adaptation.
AB  - Cement augmentation in vertebrae (vertebroplasty) is usually used to restore
      mechanical strength after spinal fracture but could also be used as a
      prophylactic treatment. So far, the mechanical competence has been determined
      immediately post-treatment, without considering long-term effects of bone
      adaptation. In this work, we investigated such long-term effects of
      vertebroplasty on the stiffness of the augmented bone by means of computational
      simulation of bone adaptation. Using micro-finite element analysis, we determined
      sites of increased mechanical stress (stress raisers) and stress shielding and,
      based on the simulations, regions with increased or decreased bone loss due to
      augmentation. Cement volumes connecting the end plates led to increased stress
      shielding and bone loss. The increased stiffness due to the augmentation,
      however, remained constant over the simulation time of 30 years. If the
      intervention was performed at an earlier time point, it did lead to more bone
      loss, but again, it did not affect long-term stability as this loss was
      compensated by bone gains in other areas. In particular, around the augmentation
      cement, bone structures were preserved, suggesting a long-term integration of the
      cement in the augmented bone. We conclude that, from a biomechanical perspective,
      the impact of vertebroplasty on the bone at the microstructural level is less
      detrimental than previously thought.

PMID- 28427316
TI  - A multiscale modelling approach to understand atherosclerosis formation: A
      patient-specific case study in the aortic bifurcation.
AB  - Atherogenesis, the formation of plaques in the wall of blood vessels, starts as a
      result of lipid accumulation (low-density lipoprotein cholesterol) in the vessel
      wall. Such accumulation is related to the site of endothelial
      mechanotransduction, the endothelial response to mechanical stimuli and
      haemodynamics, which determines biochemical processes regulating the vessel wall
      permeability. This interaction between biomechanical and biochemical phenomena is
      complex, spanning different biological scales and is patient-specific, requiring
      tools able to capture such mathematical and biological complexity in a unified
      framework. Mathematical models offer an elegant and efficient way of doing this,
      by taking into account multifactorial and multiscale processes and mechanisms, in
      order to capture the fundamentals of plaque formation in individual patients. In
      this study, a mathematical model to understand plaque and calcification locations
      is presented: this model provides a strong interpretability and physical meaning
      through a multiscale, complex index or metric (the penetration site of low
      density lipoprotein cholesterol, expressed as volumetric flux). Computed
      tomography scans of the aortic bifurcation and iliac arteries are analysed and
      compared with the results of the multifactorial model. The results indicate that
      the model shows potential to predict the majority of the plaque locations, also
      not predicting regions where plaques are absent. The promising results from this
      case study provide a proof of concept that can be applied to a larger patient
      population.

PMID- 28427317
TI  - Nonlinear homogenisation of trabecular bone: Effect of solid phase constitutive
      model.
AB  - Micro-finite element models have been extensively employed to evaluate the
      elastic properties of trabecular bone and, to a limited extent, its yield
      behaviour. The macroscopic stiffness tensor and yield surface are of special
      interest since they are essential in the prediction of bone strength and
      stability of implants at the whole bone level. While macroscopic elastic
      properties are now well understood, yield and post-yield properties are not. The
      aim of this study is to shed some light on what the effect of the solid phase
      yield criterion is on the macroscopic yield of trabecular bone for samples with
      different microstructure. Three samples with very different density were
      subjected to a large set of apparent load cases (which is important since
      physiological loading is complex and can have multiple components in stress or
      strain space) with two different solid phase yield criteria: Drucker-Prager and
      eccentric-ellipsoid. The study found that these two criteria led to small
      differences in the macroscopic yield strains for most load cases except for those
      that were compression-dominated; in these load cases, the yield strains for the
      Drucker-Prager criterion were significantly higher. Higher density samples
      resulted in higher differences between the two criteria. This work provides a
      comprehensive assessment of the effect of two different solid phase yield
      criteria on the macroscopic yield strains of trabecular bone, for a wide range of
      load cases, and for samples with different morphology.

PMID- 28427318
TI  - Load application for the contact mechanics analysis and wear prediction of total
      knee replacement.
AB  - Tibiofemoral contact forces in total knee replacement have been measured at the
      medial and lateral sites respectively using an instrumented prosthesis, and
      predicted from musculoskeletal multibody dynamics models with a reasonable
      accuracy. However, it is uncommon that the medial and lateral forces are applied
      separately to replace a total axial load according to the ISO standard in the
      majority of current finite element analyses. In this study, we quantified the
      different effects of applying the medial and lateral loads separately versus the
      traditional total axial load application on contact mechanics and wear prediction
      of a patient-specific knee prosthesis. The load application position played an
      important role under the medial-lateral load application. The loading set which
      produced the closest load distribution to the multibody dynamics model was used
      to predict the contact mechanics and wear for the prosthesis and compared with
      the total axial load application. The medial-lateral load distribution using the
      present method was found to be closer to the multibody dynamics prediction than
      the traditional total axial load application, and the maximum contact pressure
      and contact area were consistent with the corresponding load variation. The
      predicted total volumetric wear rate and area were similar between the two load
      applications. However, the split of the predicted wear volumes on the medial and
      the lateral sides was different. The lateral volumetric wear rate was 31.46%
      smaller than the medial from the traditional load application prediction, while
      from the medial-lateral load application, the lateral side was only 11.8% smaller
      than the medial. The medial-lateral load application could provide a new and more
      accurate method of load application for patient-specific preclinical contact
      mechanics and wear prediction of knee implants.

PMID- 28427319
TI  - Mechanobiological modelling of tendons: Review and future opportunities.
AB  - Tendons are adapted to carry large, repeated loads and are clinically important
      for the maintenance of musculoskeletal health in an increasing, actively ageing
      population, as well as in elite athletes. Tendons are known to adapt to
      mechanical loading. Also, their healing and disease processes are highly
      sensitive to mechanical load. Computational modelling approaches developed to
      capture this mechanobiological adaptation in tendons and other tissues have
      successfully addressed many important scientific and clinical issues. The aim of
      this review is to identify techniques and approaches that could be further
      developed to address tendon-related problems. Biomechanical models are identified
      that capture the multi-level aspects of tendon mechanics. Continuum whole tendon
      models, both phenomenological and microstructurally motivated, are important to
      estimate forces during locomotion activities. Fibril-level microstructural models
      are documented that can use these estimated forces to detail local mechanical
      parameters relevant to cell mechanotransduction. Cell-level models able to
      predict the response to such parameters are also described. A selection of
      updatable mechanobiological models is presented. These use mechanical signals,
      often continuum tissue level, along with rules for tissue change and have been
      applied successfully in many tissues to predict in vivo and in vitro outcomes.
      Signals may include scalars derived from the stress or strain tensors, or in
      poroelasticity also fluid velocity, while adaptation may be represented by
      changes to elastic modulus, permeability, fibril density or orientation. So far,
      only simple analytical approaches have been applied to tendon mechanobiology.
      With the development of sophisticated computational mechanobiological models in
      parallel with reporting more quantitative data from in vivo or clinical
      mechanobiological studies, for example, appropriate imaging, biochemical and
      histological data, this field offers huge potential for future development
      towards clinical applications.

PMID- 28427320
TI  - The role of inelastic deformations in the mechanical response of endovascular
      shape memory alloy devices.
AB  - Nickel-titanium alloys are commonly adopted for producing cardiovascular
      minimally invasive devices such as self-expandable stents, aortic valves and
      stent-grafts. These devices are subjected to cyclic loads (due to blood
      pulsatility, leg or heart movements), that can induce fatigue fracture, and may
      also be subjected to very large deformations (due to crimping procedure, a
      tortuous physiological path or overloads), that can induce material yield.
      Recently, the authors developed a new constitutive model that considers inelastic
      strains due to not-completed reverse phase transformation (not all the stress
      induced martensite turns back to austenite) or/and plasticity and their
      accumulation during cyclic loads. In this article, the model is implemented in
      the finite element code ABAQUS/Standard and it is used to investigate the effects
      of inelastic strain accumulation on endovascular nickel-titanium devices. In
      particular, the behavior of a transcatheter aortic valve is studied considering
      the following steps: (1) crimping, (2) expansion in a tube resembling a
      durability test chamber and (3) cyclic loads due to pressure variation applied on
      the inner surface of the tube. The analyses are performed twice, activating and
      not activating that part of the new model which describes the development of
      irreversible strain. From the results, it is interesting to note that plasticity
      has a very significant effect on the local material response, inducing stress
      modification from compression to tension. However, permanent deformations are
      concentrated in few zones of the stent frame and their presence does not affect
      the global behavior of the device that maintains its capability of recovering the
      original shape. In conclusion, this work suggests that at least for
      cardiovascular devices where the crimping is high (local strain may reach values
      of 8%-9%), taking into account inelastic effects due to plasticity and not
      completed reverse phase transformation can be important, and hence using a
      suitable constitutive model is recommended.

PMID- 28427321
TI  - In silico assessment of biomedical products: The conundrum of rare but not so
      rare events in two case studies.
AB  - In silico clinical trials, defined as "The use of individualized computer
      simulation in the development or regulatory evaluation of a medicinal product,
      medical device, or medical intervention," have been proposed as a possible
      strategy to reduce the regulatory costs of innovation and the time to market for
      biomedical products. We review some of the the literature on this topic, focusing
      in particular on those applications where the current practice is recognized as
      inadequate, as for example, the detection of unexpected severe adverse events too
      rare to be detected in a clinical trial, but still likely enough to be of
      concern. We then describe with more details two case studies, two successful
      applications of in silico clinical trial approaches, one relative to the
      University of Virginia/Padova simulator that the Food and Drug Administration has
      accepted as possible replacement for animal testing in the preclinical assessment
      of artificial pancreas technologies, and the second, an investigation of the
      probability of cardiac lead fracture, where a Bayesian network was used to
      combine in vivo and in silico observations, suggesting a whole new strategy of in
      silico-augmented clinical trials, to be used to increase the numerosity where
      recruitment is impossible, or to explore patients' phenotypes that are unlikely
      to appear in the trial cohort, but are still frequent enough to be of concern.

PMID- 28427322
TI  - Dental pulp pluripotent-like stem cells (DPPSC), a new stem cell population with
      chromosomal stability and osteogenic capacity for biomaterials evaluation.
AB  - BACKGROUND: Biomaterials are widely used to regenerate or substitute bone tissue.
      In order to evaluate their potential use for clinical applications, these need to
      be tested and evaluated in vitro with cell culture models. Frequently,
      immortalized osteoblastic cell lines are used in these studies. However, their
      uncontrolled proliferation rate, phenotypic changes or aberrations in mitotic
      processes limits their use in long-term investigations. Recently, we described a
      new pluripotent-like subpopulation of dental pulp stem cells derived from the
      third molars (DPPSC) that shows genetic stability and shares some pluripotent
      characteristics with embryonic stem cells. In this study we aim to describe the
      use of DPPSC to test biomaterials, since we believe that the biomaterial cues
      will be more critical in order to enhance the differentiation of pluripotent stem
      cells. METHODS: The capacity of DPPSC to differentiate into osteogenic lineage
      was compared with human sarcoma osteogenic cell line (SAOS-2). Collagen and
      titanium were used to assess the cell behavior in commonly used biomaterials. The
      analyses were performed by flow cytometry, alkaline phosphatase and
      mineralization stains, RT-PCR, immunohistochemistry, scanning electron
      microscopy, Western blot and enzymatic activity. Moreover, the genetic stability
      was evaluated and compared before and after differentiation by short-comparative
      genomic hybridization (sCGH). RESULTS: DPPSC showed excellent differentiation
      into osteogenic lineages expressing bone-related markers similar to SAOS-2. When
      cells were cultured on biomaterials, DPPSC showed higher initial adhesion levels.
      Nevertheless, their osteogenic differentiation showed similar trend among both
      cell types. Interestingly, only DPPSC maintained a normal chromosomal dosage
      before and after differentiation on 2D monolayer and on biomaterials.
      CONCLUSIONS: Taken together, these results promote the use of DPPSC as a new
      pluripotent-like cell model to evaluate the biocompatibility and the
      differentiation capacity of biomaterials used in bone regeneration.

PMID- 28427323
TI  - Detection of QTL for traits related to adaptation to sub-optimal climatic
      conditions in chickens.
AB  - BACKGROUND: Growth traits can be used as indicators of adaptation to sub-optimal
      conditions. The current study aimed at identifying quantitative trait loci (QTL)
      that control performance under variable temperature conditions in chickens.
      METHODS: An F2 population was produced by crossing the Taiwan Country chicken L2
      line (selected for body weight, comb area, and egg production) with an
      experimental line of Rhode Island Red layer R- (selected for low residual feed
      consumption). A total of 844 animals were genotyped with the 60 K Illumina single
      nucleotide polymorphism (SNP) chip. Whole-genome interval linkage mapping and a
      genome-wide association study (GWAS) were performed for body weight at 0, 4, 8,
      12, and 16 weeks of age, shank length at 8 weeks of age, size of comb area at 16
      weeks of age, and antibody response to sheep red blood cells at 11 weeks of age
      (7 and 14 days after primary immunization). Relevant genes were identified based
      on functional annotation of candidate genes and potentially relevant SNPs were
      detected by comparing whole-genome sequences of several birds between the
      parental lines. RESULTS: Whole-genome QTL analysis revealed 47 QTL and 714
      effects associated with 178 SNPs were identified by GWAS with 5% Bonferroni
      genome-wide significance. Little overlap was observed between the QTL and GWAS
      results, with only two chromosomal regions detected by both approaches, i.e. one
      on GGA24 (GGA for Gallus gallus chromosome) for BW04 and one on GGAZ for six
      growth-related traits. Based on whole-genome sequence, differences between the
      parental lines based on several birds were screened in the genome-wide QTL
      regions and in a region detected by both methods, resulting in the identification
      of 106 putative candidate genes with a total of 15,443 SNPs, of which 41 were
      missense and 1698 were not described in the dbSNP archive. CONCLUSIONS: The QTL
      detected in this study for growth and morphological traits likely influence
      adaptation of chickens to sub-tropical climate. Using whole-genome sequence data,
      we identified candidate SNPs for further confirmation of QTL in the F2 design. A
      strong QTL effect found on GGAZ underlines the importance of sex-linked
      inheritance for growth traits in chickens.

PMID- 28427324
TI  - Genomic prediction from observed and imputed high-density ovine genotypes.
AB  - BACKGROUND: Genomic prediction using high-density (HD) marker genotypes is
      expected to lead to higher prediction accuracy, particularly for more
      heterogeneous multi-breed and crossbred populations such as those in sheep and
      beef cattle, due to providing stronger linkage disequilibrium between single
      nucleotide polymorphisms and quantitative trait loci controlling a trait. The
      objective of this study was to evaluate a possible improvement in genomic
      prediction accuracy of production traits in Australian sheep breeds based on HD
      genotypes (600k, both observed and imputed) compared to prediction based on 50k
      marker genotypes. In particular, we compared improvement in prediction accuracy
      of animals that are more distantly related to the reference population and across
      sheep breeds. METHODS: Genomic best linear unbiased prediction (GBLUP) and a
      Bayesian approach (BayesR) were used as prediction methods using whole or subsets
      of a large multi-breed/crossbred sheep reference set. Empirical prediction
      accuracy was evaluated for purebred Merino, Border Leicester, Poll Dorset and
      White Suffolk sire breeds according to the Pearson correlation coefficient
      between genomic estimated breeding values and breeding values estimated based on
      a progeny test in a separate dataset. RESULTS: Results showed a small absolute
      improvement (0.0 to 8.0% and on average 2.2% across all traits) in prediction
      accuracy of purebred animals from HD genotypes when prediction was based on the
      whole dataset. Greater improvement in prediction accuracy (1.0 to 12.0% and on
      average 5.2%) was observed for animals that were genetically lowly related to the
      reference set while it ranged from 0.0 to 5.0% for across-breed prediction. On
      average, no significant advantage was observed with BayesR compared to GBLUP.

PMID- 28427325
TI  - Global analysis of protein lysine succinylation profiles in common wheat.
AB  - BACKGROUND: Protein lysine succinylation is an important post-translational
      modification and plays a critical regulatory role in almost every aspects of cell
      metabolism in both eukaryotes and prokaryotes. Common wheat is one of the major
      global cereal crops. However, to date, little is known about the functions of
      lysine succinylation in this plant. Here, we performed a global analysis of
      lysine succinylation in wheat and examined its overlap with lysine acetylation.
      RESULTS: In total, 330 lysine succinylated modification sites were identified in
      173 proteins. Bioinformatics analysis showed that the modified proteins are
      distributed in multiple subcellular compartments and are involved in a wide
      variety of biological processes such as photosynthesis and the Calvin-Benson
      cycle, suggesting an important role for lysine succinylation in these processes.
      Five putative succinylation motifs were identified. A protein interaction network
      analysis revealed that diverse interactions are modulated by protein
      succinylation. Moreover, 21 succinyl-lysine sites were found to be acetylated at
      the same position, and 33 proteins were modified by both acetylation and
      succinylation, suggesting an extensive overlap between succinylation and
      acetylation in common wheat. Comparative analysis indicated that lysine
      succinylation is conserved between common wheat and Brachypodium distachyon.
      CONCLUSIONS: These results suggest that lysine succinylation is involved in
      diverse biological processes, especially in photosynthesis and carbon fixation.
      This systematic analysis represents the first global analysis of lysine
      succinylation in common wheat and provides an important resource for exploring
      the physiological role of lysine succinylation in this cereal crop and likely in
      all plants.

PMID- 28427326
TI  - No evidence for strong cytonuclear conflict over sex allocation in a
      simultaneously hermaphroditic flatworm.
AB  - BACKGROUND: Cytoplasmic sex allocation distorters, which arise from cytonuclear
      conflict over the optimal investment into male versus female reproductive
      function, are some of the best-researched examples for genomic conflict. Among
      hermaphrodites, many such distorters have been found in plants, while, to our
      knowledge, none have been clearly documented in animals. METHODS: Here we provide
      a quantitative test for cytonuclear conflict over sex allocation in the
      simultaneously hermaphroditic flatworm Macrostomum lignano. We used a
      quantitative genetic breeding design, employing pair-wise crosses of 2 * 15
      independent inbred lines, to partition the phenotypic variance in several traits
      (including sex allocation) into its nuclear and cytoplasmic components. RESULTS:
      Although the nuclear genetic background had a significant effect on all traits
      analyzed, we found significant cytoplasmic genetic variation only for ovary size,
      there explaining just 4.1% of the variance. A subsequent statistical power
      analysis showed that the experimental design had considerable power to detect
      cytonuclear interactions. CONCLUSION: We conclude that there were no strong
      effects of cytonuclear conflict in the studied populations, possibly because the
      usually compact mitochondrial genomes in animals have a lower evolvability than
      the large mitochondrial genomes in plants or because the sampled populations
      currently do not harbor variation at putative distorter and/or the restorer loci.

PMID- 28427327
TI  - Analysis of transcriptome data reveals multifactor constraint on codon usage in
      Taenia multiceps.
AB  - BACKGROUND: Codon usage bias (CUB) is an important evolutionary feature in
      genomes that has been widely observed in many organisms. However, the synonymous
      codon usage pattern in the genome of T. multiceps remains to be clarified. In
      this study, we analyzed the codon usage of T. multiceps based on the
      transcriptome data to reveal the constraint factors and to gain an improved
      understanding of the mechanisms that shape synonymous CUB. RESULTS: Analysis of a
      total of 8,620 annotated mRNA sequences from T. multiceps indicated only a weak
      codon bias, with mean GC and GC3 content values of 49.29% and 51.43%,
      respectively. Our analysis indicated that nucleotide composition, mutational
      pressure, natural selection, gene expression level, amino acids with grand
      average of hydropathicity (GRAVY) and aromaticity (Aromo) and the effective
      selection of amino-acids all contributed to the codon usage in T. multiceps.
      Among these factors, natural selection was implicated as the major factor
      affecting the codon usage variation in T. multiceps. The codon usage of ribosome
      genes was affected mainly by mutations, while the essential genes were affected
      mainly by selection. In addition, 21codons were identified as "optimal codons".
      Overall, the optimal codons were GC-rich (GC:AU, 41:22), and ended with G or C
      (except CGU). Furthermore, different degrees of variation in codon usage were
      found between T. multiceps and Escherichia coli, yeast, Homo sapiens. However,
      little difference was found between T. multiceps and Taenia pisiformis.
      CONCLUSIONS: In this study, the codon usage pattern of T. multiceps was analyzed
      systematically and factors affected CUB were also identified. This is the first
      study of codon biology in T. multiceps. Understanding the codon usage pattern in
      T. multiceps can be helpful for the discovery of new genes, molecular genetic
      engineering and evolutionary studies.

PMID- 28427328
TI  - Erratum to: The nasopharyngeal microbiota of beef cattle before and after
      transport to a feedlot.

PMID- 28427329
TI  - Cross-disorder comparative analysis of comorbid conditions reveals novel autism
      candidate genes.
AB  - BACKGROUND: Numerous studies have highlighted the elevated degree of comorbidity
      associated with autism spectrum disorder (ASD). These comorbid conditions may add
      further impairments to individuals with autism and are substantially more
      prevalent compared to neurotypical populations. These high rates of comorbidity
      are not surprising taking into account the overlap of symptoms that ASD shares
      with other pathologies. From a research perspective, this suggests common
      molecular mechanisms involved in these conditions. Therefore, identifying crucial
      genes in the overlap between ASD and these comorbid disorders may help unravel
      the common biological processes involved and, ultimately, shed some light in the
      understanding of autism etiology. RESULTS: In this work, we used a two-fold
      systems biology approach specially focused on biological processes and gene
      networks to conduct a comparative analysis of autism with 31 frequently comorbid
      disorders in order to define a multi-disorder subcomponent of ASD and predict new
      genes of potential relevance to ASD etiology. We validated our predictions by
      determining the significance of our candidate genes in high throughput
      transcriptome expression profiling studies. Using prior knowledge of disease
      related biological processes and the interaction networks of the disorders
      related to autism, we identified a set of 19 genes not previously linked to ASD
      that were significantly differentially regulated in individuals with autism. In
      addition, these genes were of potential etiologic relevance to autism, given
      their enriched roles in neurological processes crucial for optimal brain
      development and function, learning and memory, cognition and social behavior.
      CONCLUSIONS: Taken together, our approach represents a novel perspective of
      autism from the point of view of related comorbid disorders and proposes a model
      by which prior knowledge of interaction networks may enlighten and focus the
      genome-wide search for autism candidate genes to better define the genetic
      heterogeneity of ASD.

PMID- 28427330
TI  - Pan genome and CRISPR analyses of the bacterial fish pathogen Moritella viscosa.
AB  - BACKGROUND: Winter-ulcer Moritella viscosa infections continue to be a
      significant burden in Atlantic salmon (Salmo salar L.) farming. M. viscosa
      comprises two main clusters that differ in genetic variation and phenotypes
      including virulence. Horizontal gene transfer through acquisition and loss of
      mobile genetic elements (MGEs) is a major driving force of bacterial
      diversification. To gain insight into genomic traits that could affect sublineage
      evolution within this bacterium we examined the genome sequences of twelve M.
      viscosa strains. Matches between M. viscosa clustered, regularly interspaced,
      short palindromic, repeats and associated cas genes (CRISPR-Cas) were analysed to
      correlate CRISPR-Cas with adaptive immunity against MGEs. RESULTS: The
      comparative genomic analysis of M. viscosa isolates from across the North
      Atlantic region and from different fish species support delineation of M. viscosa
      into four phylogenetic lineages. The results showed that M. viscosa carries two
      distinct variants of the CRISPR-Cas subtype I-F systems and that CRISPR features
      follow the phylogenetic lineages. A subset of the spacer content match prophage
      and plasmid genes dispersed among the M. viscosa strains. Further analysis
      revealed that prophage and plasmid-like element distribution were reflected in
      the content of the CRISPR-spacer profiles. CONCLUSIONS: Our data suggests that
      CRISPR-Cas mediated interactions with MGEs impact genome properties among M.
      viscosa, and that patterns in spacer and MGE distributions are linked to strain
      relationships.

PMID- 28427331
TI  - Erratum to: More Comprehensive Forensic Genetic Marker Analyses for Accurate
      Human Remains Identification Using Massively Parallel DNA Sequencing.

PMID- 28427332
TI  - Interrater and test-retest reliability and validity of the Norwegian version of
      the BESTest and mini-BESTest in people with increased risk of falling.
AB  - BACKGROUND: The Balance Evaluation Systems Test (BESTest) was developed to assess
      underlying systems for balance control in order to be able to individually tailor
      rehabilitation interventions to people with balance disorders. A short form, the
      Mini-BESTest, was developed as a screening test. The study aimed to assess
      interrater and test-retest reliability of the Norwegian version of the BESTest
      and the Mini-BESTest in community-dwelling people with increased risk of falling
      and to assess concurrent validity with the Fall Efficacy Scale-International (FES
      I), and it was an observational study with a cross-sectional design. METHODS:
      Forty-two persons with increased risk of falling (elderly over 65 years of age,
      persons with a history of stroke or Multiple Sclerosis) were assessed twice by
      two raters. Relative reliability was analysed with Intraclass Correlation
      Coefficient (ICC), and absolute reliability with standard error of measurement
      (SEM) and smallest detectable change (SDC). Concurrent validity was assessed
      against the FES-I using Spearman's rho. RESULTS: The BESTest showed very good
      interrater reliability (ICC = 0.98, SEM = 1.79, SDC95 = 5.0) and test-retest
      reliability (rater A/rater B = ICC = 0.89/0.89, SEM = 3.9/4.3, SDC95 =
      10.8/11.8). The Mini-BESTest also showed very good interrater reliability (ICC =
      0.95, SEM = 1.19, SDC95 = 3.3) and test-retest reliability (rater A/rater B = ICC
      = 0.85/0.84, SEM = 1.8/1.9, SDC95 = 4.9/5.2). The correlations were moderate
      between the FES-I and both the BESTest and the Mini-BESTest (Spearman's rho -0.51
      and-0.50, p < 0.01). CONCLUSION: The BESTest and its short form, the Mini
      BESTest, showed very good interrater and test-retest reliability when assessed in
      a heterogeneous sample of people with increased risk of falling. The concurrent
      validity measured against the FES-I showed moderate correlation. The results are
      comparable with earlier studies and indicate that the Norwegian versions can be
      used in daily clinic and in research.

PMID- 28427333
TI  - The experiences of physiotherapists treating people with dementia who fracture
      their hip.
AB  - BACKGROUND: It is estimated that people with dementia are approximately three
      times more likely to fracture their hip than sex and age matched controls. A
      report by the Chartered Society of Physiotherapy found that this population have
      poor access to rehabilitation as inpatients and in the community. A recent
      scoping review found a paucity of research in this area, indeed there has been no
      qualitative research undertaken with physiotherapists. In order to address this
      evidence gap, the aim of this current study was to explore the experiences of
      physiotherapists treating this population. METHODS: Semi-structured interviews
      with physiotherapists were undertaken in order to gain an in-depth understanding
      of how they manage this population. Physiotherapists were recruited from all over
      the UK and a purposive sampling strategy was employed. Thematic analysis was
      utilised. RESULTS: A total of 12 physiotherapists were interviewed, at which
      stage data saturation was reached as no new themes were emerging. The
      participants had a broad range of experience both in physical and mental health
      settings. Analysis identified three separate themes: challenges, "thinking
      outside the box" and realising potential. Physiotherapists felt significant
      pressures and challenges regarding many aspects of the management of this
      population. Mainly this was the result of pressures placed on them by guidelines
      and targets that may not be achievable or appropriate for those with dementia.
      The challenges and importance of risk taking was also highlighted for this
      population with an appreciation that standard treatment techniques may need
      adapting. "Rehabilitation potential" was highlighted as an important
      consideration, but challenging to determine. CONCLUSION: Interventions for the
      management of people with dementia and hip fracture need to consider that a
      traditional biomedical physiotherapy approach may not be the most appropriate
      approach to use with this population. However physiotherapists reported feeling
      pressurised to conform to a biomedical approach.

PMID- 28427334
TI  - The impact of the mode of survey administration on estimates of daily smoking for
      mobile phone only users.
AB  - BACKGROUND: Over the past decade, there have been substantial changes in landline
      and mobile phone ownership, with a substantial increase in the proportion of
      mobile-only households. Estimates of daily smoking rates for the mobile phone
      only (MPO) population have been found to be substantially higher than the rest of
      the population and telephone surveys that use a dual sampling frame (landline and
      mobile phones) are now considered best practice. Smoking is seen as an
      undesirable behaviour; measuring such behaviours using an interviewer may lead to
      lower estimates when using telephone based surveys compared to self-administered
      approaches. This study aims to assess whether higher daily smoking estimates
      observed for the mobile phone only population can be explained by administrative
      features of surveys, after accounting for differences in the phone ownership
      population groups. METHODS: Data on New South Wales (NSW) residents aged 18 years
      or older from the NSW Population Health Survey (PHS), a telephone survey, and the
      National Drug Strategy Household Survey (NDSHS), a self-administered survey, were
      combined, with weights adjusted to match the 2013 population. Design-adjusted
      prevalence estimates and odds ratios were calculated using survey analysis
      procedures available in SAS 9.4. RESULTS: Both the PHS and NDSHS gave the same
      estimates for daily smoking (12%) and similar estimates for MPO users (20% and
      18% respectively). Pooled data showed that daily smoking was 19% for MPO users,
      compared to 10% for dual phone owners, and 12% for landline phone only users.
      Prevalence estimates for MPO users across both surveys were consistently higher
      than other phone ownership groups. Differences in estimates for the MPO
      population compared to other phone ownership groups persisted even after
      adjustment for the mode of collection and demographic factors. CONCLUSIONS: Daily
      smoking rates were consistently higher for the mobile phone only population and
      this was not driven by the mode of survey collection. This supports the assertion
      that the use of a dual sampling frame addresses coverage issues that would
      otherwise be present in telephone surveys that only made use of a landline
      sampling frame.

PMID- 28427335
TI  - Cholesterol esterification in plasma as a biomarker for liver function and
      prediction of mortality.
AB  - BACKGROUND: Advanced stages of liver cirrhosis lead to a dramatically increased
      mortality. For valid identification of these patients suitable biomarkers are
      essential. The most important biomarkers for liver function are bilirubin and
      prothrombin time expressed as International Normalized Ratio (INR). However, the
      influence of several anticoagulants on the prothrombin time limits its diagnostic
      value. Aim of this study was the evaluation of cholesterol esterification (CE)
      fraction (esterified cholesterol vs. total cholesterol) as an alternative
      biomarker for liver synthesis and mortality prediction. Under physiological
      conditions the CE fraction in blood is closely regulated by lecithin-cholesterol
      acyltransferase (LCAT) which is produced in the liver. METHODS: One hundred forty
      two patients with liver disease clinically considered for orthotopic liver
      transplant for different indications were enrolled in the study. One patient was
      excluded because of the intake of a direct oral factor Xa inhibitor which has a
      strong impact on prothrombin time. RESULTS: Results of CE fraction were in good
      agreement with INR (R2 = 0.73; p < 0.001). In patients who died or survived
      within three months mean CE fraction was 56% vs. 74% (p < 0.001) and mean INR was
      2.0 vs. 1.3 (p < 0.001), respectively. The predictive value of CE fraction for
      three-month mortality risk was higher compared to INR (p = 0.04). Results for one
      year mortality were comparable. CONCLUSIONS: The cholesterol esterification
      fraction is a valid biomarker for liver synthesis and allows reliable prediction
      of mortality. In contrast to INR, it is independent of anticoagulation and other
      analytical limitations of coagulation tests.

PMID- 28427336
TI  - Protocol for the home hazards removal program (HARP) study: a pragmatic,
      randomized clinical trial and implementation study.
AB  - BACKGROUND: Falls remain the leading cause of injury, long-term disability,
      premature institutionalization, and injury-related mortality in the older adult
      population. Home modifications, when delivered by occupational therapists, can
      reduce falls among high-risk community-dwelling older adults by 39%. However,
      home-modification implementation is not standard practice in the United States.
      The goal of the Home Hazard Removal Program (HARP) study is to implement an
      evidence-based home modification intervention for older adults designed to reduce
      the incidence of falls through an aging services network. METHODS: We will
      conduct a hybrid effectiveness/implementation trial of 300 older adults at risk
      for a fall who are randomized and followed for 12 months. Participants who are
      randomized to treatment will receive the home modification intervention provided
      by an occupational therapist in addition to usual care, defined as continued
      services from the area agency on aging. We will compare the effectiveness of the
      program and usual care using survival analysis with the time to the first fall
      over 12 months as the primary outcome of interest. Secondary outcomes include
      daily activity performance, fall self-efficacy, and health-related quality of
      life. Fidelity, dose, adherence, safety, cost, and health care utilization will
      also be examined in the implementation component of this study. DISCUSSION: This
      intervention targets an underserved, difficult to reach population of older
      adults. The tailored approach of the study intervention is a strength in
      improving adherence, as each recommendation is individualized to be acceptable to
      the participant. The effectiveness/implementation design of the study allows for
      rapid dissemination of results and implementation of the intervention in a United
      States social services agency. TRIAL REGISTRATION: Clinicaltrials.gov identifier:
      NCT02392013 . Retrospectively registered on March 5, 2015.

PMID- 28427338
TI  - 'Working is out of the question': a qualitative text analysis of medical
      certificates of disability.
AB  - BACKGROUND: Medical certificates influence the distribution of economic benefits
      in welfare states; however, the qualitative aspects of these texts remain largely
      unexplored. The present study is the first systematic investigation done of these
      texts. Our aim was to investigate how GPs select and mediate information about
      their patients' health and how they support their conclusions about illness,
      functioning and fitness for work in medical certificates. METHODS: We performed a
      textual analysis of thirty-three medical certificates produced by general
      practitioners (GP) in Norway at the request of the Norwegian Labour and Welfare
      Administration (NAV).The certificates were subjected to critical reading using
      the combined analytic methods of narratology and linguistics. RESULTS: Some of
      the medical information was unclear, ambiguous, and possibly misleading.
      Evaluations of functioning related to illness were scarce or absent, regardless
      of diagnosis, and, hence, the basis of working incapacity was unclear. Voices in
      the text frequently conflated, obscuring the source of speaker. In some
      documents, the expert's subtle use of language implied doubts about the
      claimant's credibility, but explicit advocacy also occurred. GPs show little
      insight into their patients' working lives, but rather than express uncertainty
      and incompetence, they may resort to making too absolute and too general
      statements about patients' working capacity, and fail to report thorough
      assessments. CONCLUSIONS: A number of the texts in our material may not function
      as sufficient or reliable sources for making decisions regarding social benefits.
      Certificates as these may be deficient for several reasons, and textual
      incompetence may be one of them. Physicians in Norway receive no systematic
      training in professional writing. High-quality medical certificates, we believe,
      might be economical in the long term: it might increase the efficiency with which
      NAV processes cases and save costs by eliminating the need for unnecessary and
      expensive specialist reports. Moreover, correct and coherent medical certificates
      can strengthen legal protection for claimants. Eventually, reducing advocacy in
      these documents may contribute to a fairer evaluation of whether claimants are
      eligible for disability benefits or not. Therefore, we believe that professional
      writing skills should be validated as an important part of medical practice and
      should be integrated in medical schools and in further education as a discipline
      in its own right, preferably involving humanities professors.

PMID- 28427337
TI  - Treatment-seeking behaviour in low- and middle-income countries estimated using a
      Bayesian model.
AB  - BACKGROUND: Seeking treatment in formal healthcare for uncomplicated infections
      is vital to combating disease in low- and middle-income countries (LMICs).
      Healthcare treatment-seeking behaviour varies within and between communities and
      is modified by socio-economic, demographic, and physical factors. As a result, it
      remains a challenge to quantify healthcare treatment-seeking behaviour using a
      metric that is comparable across communities. Here, we present an application for
      transforming individual categorical responses (actions related to fever) to a
      continuous probabilistic estimate of fever treatment for one country in Sub
      Saharan Africa (SSA). METHODS: Using nationally representative household survey
      data from the 2013 Demographic and Health Survey (DHS) in Namibia, individual
      level responses (n = 1138) were linked to theoretical estimates of travel time to
      the nearest public or private health facility. Bayesian Item Response Theory
      (IRT) models were fitted via Markov Chain Monte Carlo (MCMC) simulation to
      estimate parameters related to fever treatment and estimate probability of
      treatment for children under five years. Different models were implemented to
      evaluate computational needs and the effect of including predictor variables such
      as rurality. The mean treatment rates were then estimated at regional level.
      RESULTS: Modelling results suggested probability of fever treatment was highest
      in regions with relatively high incidence of malaria historically. The minimum
      predicted threshold probability of seeking treatment was 0.3 (model 1: 0.340; 95%
      CI 0.155-0.597), suggesting that even in populations at large distances from
      facilities, there was still a 30% chance of an individual seeking treatment for
      fever. The agreement between correctly predicted probability of treatment at
      individual level based on a subset of data (n = 247) was high (AUC = 0.978), with
      a sensitivity of 96.7% and a specificity of 75.3%. CONCLUSION: We have shown how
      individual responses in national surveys can be transformed to probabilistic
      measures comparable at population level. Our analysis of household survey data on
      fever suggested a 30% baseline threshold for fever treatment in Namibia. However,
      this threshold level is likely to vary by country or endemicity. Although our
      focus was on fever treatment, the methodology outlined can be extended to
      multiple health seeking behaviours captured in routine national survey data and
      to other infectious diseases.

PMID- 28427339
TI  - Cardiovascular disease risk among Chinese antiretroviral-naive adults with
      advanced HIV disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) is an important cause of mortality among
      HIV-infected patients, however little is known about the burden of CVD among this
      population in Asia. We sought to quantify prevalence of CVD risk factors, 10-year
      CVD risk, and patterns of CVD risk factor treatment in a group of individuals
      with HIV in China. METHODS: We retrospectively analyzed baseline data from
      treatment-naive HIV-infected adults enrolled in two multicenter clinical trials
      in China. Data regarding CVD risk factors such as smoking, hypertension,
      diabetes, dyslipidemia and obesity were assessed. The Framingham Risk Score (FRS)
      and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk scores were
      calculated to estimate 10-year CVD risk. The American College of
      Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease
      (ASCVD) Risk Score was used to identify individuals meeting criteria for lipid
      lowering therapy. RESULTS: In total, 973 patients were included in the analysis.
      Mean age was 36.0 +/- 10.2 years and 74.2% were men. The most common CVD risk
      factors were dyslipidemia (51.7%) and smoking (23.7%). Prevalence of
      hypertension, diabetes and obesity were 8.4%, 4.6% and 1.0%, respectively. Over
      65% of patients had at least one CVD risk factor. The prevalence of 10-year risk
      of CVD >=10% was 4.5% based upon FRS and was 3.3% based upon D:A:D risk score.
      Few patients with dyslipidemia, hypertension or diabetes were on treatment.
      CONCLUSIONS: CVD risk factors are common but under-treated among Chinese
      treatment-naive individuals with HIV. Future interventions should focus on
      training HIV providers to appropriately recognize and manage CVD risk factors
      during routine clinical assessments.

PMID- 28427340
TI  - Does the association between adherence to statin medications and mortality depend
      on measurement approach? A retrospective cohort study.
AB  - BACKGROUND: The aim of this study was to examine the relationship between
      mortality and statin adherence using two different approaches to adherence
      measurement (summary versus repeated-measures). METHODS: A retrospective cohort
      study was conducted using administrative data from Saskatchewan, Canada between
      1994 and 2008. Eligible individuals received a prescription for a statin
      following hospitalization for acute coronary syndrome (ACS). Adherence was
      measured using proportion of days covered (PDC) expressed either as: 1) a fixed
      summary measure, or 2) as a repeatedly measured covariate. Multivariable Cox
      proportional hazards models were used to estimate the association between
      adherence and mortality. RESULTS: Among 9,051 individuals, optimal adherence
      (>=80%) modeled with a fixed summary measure was not associated with mortality
      benefits (adjusted HR 0.97, 95% CI 0.86 to 1.09, p = 0.60). In contrast, repeated
      measures approach resulted in a significant 25% reduction in the risk of death
      (adjusted HR 0.75, 95% CI 0.67 to 0.85, p < 0.01). CONCLUSIONS: Unlike the
      summary measure, the repeated measures approach produces a significant reduction
      of all-cause mortality with optimal adherence. This effect may be a result of the
      repeated measures approach being more sensitive, or more prone to survival bias.
      Our findings clearly demonstrate the need to undertake (and report) multiple
      approaches when assessing the benefits of medication adherence.

PMID- 28427341
TI  - Reactive oxygen species mediate tapetal programmed cell death in tobacco and
      tomato.
AB  - BACKGROUND: Hybrid vigor is highly valued in the agricultural industry. Male
      sterility is an important trait for crop breeding. Pollen development is under
      strict control of both gametophytic and sporophytic factors, and defects in this
      process can result in male sterility. Both in the dicot Arabidopsis and in the
      moncot rice, proper timing of programmed cell death (PCD) in the tapetum ensures
      pollen development. Dynamic ROS levels have been reported to control tapetal PCD,
      and thus pollen development, in Arabidopsis and rice. However, it was unclear
      whether it is evolutionarily conserved, as only those two distantly related
      species were studied. RESULTS: Here, we performed histological analyses of anther
      development of two economically important dicot species, tobacco and tomato. We
      identified the same ROS amplitude during anther development in these two species
      and found that dynamic ROS levels correlate with the initiation and progression
      of tapetal PCD. We further showed that manipulating ROS levels during anther
      development severely impaired pollen development, resulting in partial male
      sterility. Finally, real-time quantitative PCR showed that several tobacco and
      tomato RBOHs, encoding NADPH oxidases, are preferentially expressed in anthers.
      CONCLUSION: This study demonstrated evolutionarily conserved ROS amplitude during
      anther development by examining two commercially important crop species in the
      Solanaceae. Manipulating ROS amplitude through genetic interference of RBOHs
      therefore may provide a practical way to generate male sterile plants.

PMID- 28427342
TI  - Intermittent parathyroid hormone (PTH) promotes cementogenesis and alleviates the
      catabolic effects of mechanical strain in cementoblasts.
AB  - BACKGROUND: External root resorption, commonly starting from cementum, is a
      severe side effect of orthodontic treatment. In this pathological process and
      repairing course followed, cementoblasts play a significant role. Previous
      studies implicated that parathyroid hormone (PTH) could act on committed
      osteoblast precursors to promote differentiation, and inhibit apoptosis. But
      little was known about the role of PTH in cementoblasts. The purpose of this
      study was to investigate the effects of intermittent PTH on cementoblasts and its
      influence after mechanical strain treatment. RESULTS: Higher levels of
      cementogenesis- and differentiation-related biomarkers (bone sialoprotein (BSP),
      osteocalcin (OCN), Collagen type I (COL1) and Osterix (Osx)) were shown in 1-3
      cycles of intermittent PTH treated groups than the control group. Additionally,
      intermittent PTH increased alkaline phosphatase (ALP) activity and mineralized
      nodules formation, as measured by ALP staining, quantitative ALP assay, Alizarin
      red S staining and quantitative calcium assay. The morphology of OCCM-30 cells
      changed after mechanical strain exertion. Expression of BSP, ALP, OCN,
      osteopontin (OPN) and Osx was restrained after 18 h mechanical strain.
      Furthermore, intermittent PTH significantly increased the expression of
      cementogenesis- and differentiation-related biomarkers in mechanical strain
      treated OCCM-30 cells. CONCLUSIONS: Taken together, these data suggested that
      intermittent PTH promoted cementum formation through activating cementogenesis-
      and differentiation-related biomarkers, and attenuated the catabolic effects of
      mechanical strain in immortalized cementoblasts OCCM-30.

PMID- 28427343
TI  - Loss of pericyte smoothened activity in mice with genetic deficiency of leptin.
AB  - BACKGROUND: Obesity is associated with multiple diseases, but it is unclear how
      obesity promotes progressive tissue damage. Recovery from injury requires repair,
      an energy-expensive process that is coupled to energy availability at the
      cellular level. The satiety factor, leptin, is a key component of the sensor that
      matches cellular energy utilization to available energy supplies. Leptin
      deficiency signals energy depletion, whereas activating the Hedgehog pathway
      drives energy-consuming activities. Tissue repair is impaired in mice that are
      obese due to genetic leptin deficiency. Tissue repair is also blocked and obesity
      enhanced by inhibiting Hedgehog activity. We evaluated the hypothesis that loss
      of leptin silences Hedgehog signaling in pericytes, multipotent leptin-target
      cells that regulate a variety of responses that are often defective in obesity,
      including tissue repair and adipocyte differentiation. RESULTS: We found that
      pericytes from liver and white adipose tissue require leptin to maintain
      expression of the Hedgehog co-receptor, Smoothened, which controls the activities
      of Hedgehog-regulated Gli transcription factors that orchestrate gene expression
      programs that dictate pericyte fate. Smoothened suppression prevents liver
      pericytes from being reprogrammed into myofibroblasts, but stimulates adipose
      derived pericytes to become white adipocytes. Progressive Hedgehog pathway decay
      promotes senescence in leptin-deficient liver pericytes, which, in turn, generate
      paracrine signals that cause neighboring hepatocytes to become fatty and less
      proliferative, enhancing vulnerability to liver damage. CONCLUSIONS: Leptin
      responsive pericytes evaluate energy availability to inform tissue construction
      by modulating Hedgehog pathway activity and thus, are at the root of progressive
      obesity-related tissue pathology. Leptin deficiency inhibits Hedgehog signaling
      in pericytes to trigger a pericytopathy that promotes both adiposity and obesity
      related tissue damage.

PMID- 28427344
TI  - Genome-wide identification of genes probably relevant to the adaptation of
      schizothoracins (Teleostei: Cypriniformes) to the uplift of the Qinghai-Tibet
      Plateau.
AB  - BACKGROUND: Molecular adaptation to the severe environments present during the
      uplift of the Qinghai-Tibet Plateau has attracted the attention of researchers.
      The divergence of the three specialization groups of schizothoracins (Primitive,
      Specialized and Highly Specialized) may correspond to the three phases of plateau
      uplift. Based on the transcripts of representative species of the three
      specialized groups and an outgroup, genes in schizothoracins that may have played
      important roles during the adaptation to new environments were investigated.
      RESULTS: The contigs of Gymnodiptychus dybowskii and Schizothorax pseudaksaiensis
      were compared with those of Gymnocypris przewalskii ganzihonensis and the
      outgroup Sinocyclocheilus angustiporus, and 5,894 ortholog groups with an
      alignment length longer than 90 nt after deleting gaps were retained.
      Evolutionary analyses indicated that the average evolutionary rate of the branch
      leading to the Specialized group was faster than that of the branch leading to
      the Highly Specialized group. Moreover, the numbers of gene categories in which
      more than half of the genes evolved faster than the average values of the genome
      were 117 and 15 along the branches leading to the Specialized and Highly
      Specialized groups, respectively. A total of 40, 36, and 55 genes were likely
      subject to positive selection along the branches leading to the Primitive,
      Specialized and Highly Specialized groups, respectively, and many of these genes
      are likely relevant to adaptation to the cold temperatures, low oxygen
      concentrations, and strong ultraviolet radiation that result from elevation.
      CONCLUSIONS: By selecting representative species of the three groups of
      schizothoracins and applying next-generation sequencing technology, several
      candidate genes corresponding to adaptation to the three phases of plateau uplift
      were identified. Some of the genes identified in this report that were likely
      subject to positive selection are good candidates for subsequent evolutionary and
      functional analyses of adaptation to high altitude.

PMID- 28427345
TI  - Variation in GP decisions on antihypertensive treatment in oldest-old and frail
      individuals across 29 countries.
AB  - BACKGROUND: In oldest-old patients (>80), few trials showed efficacy of treating
      hypertension and they included mostly the healthiest elderly. The resulting lack
      of knowledge has led to inconsistent guidelines, mainly based on systolic blood
      pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high
      prevalence in oldest-old. This may lead to variation how General Practitioners
      (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs
      in oldest-olds across countries and to identify the role of frailty in that
      decision. METHODS: Using a survey, we compared treatment decisions in cases of
      oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start
      antihypertensive treatment in each case. In 2016, we invited GPs in Europe,
      Brazil, Israel, and New Zealand. We compared the percentage of cases that would
      be treated per countries. A logistic mixed-effects model was used to derive odds
      ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD,
      and GP characteristics (sex, location and prevalence of oldest-old per GP office,
      and years of experience). The mixed-effects model was used to account for the
      multiple assessments per GP. RESULTS: The 29 countries yielded 2543 participating
      GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of
      oldest-old in their offices, 38% and had >20 years of experience. Across
      countries, considerable variation was found in the decision to start
      antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29
      (83%) countries, frailty was associated with GPs' decision not to start treatment
      even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48
      0.59; ORs per country 0.11-1.78). CONCLUSIONS: Across countries, we found
      considerable variation in starting antihypertensive medication in oldest-old. The
      frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive
      treatment. Future hypertension trials should also include frail patients to
      acquire evidence on the efficacy of antihypertensive treatment in oldest-old
      patients with frailty, with the aim to get evidence-based data for clinical
      decision-making.

PMID- 28427346
TI  - Karyotypic evolution of the Medicago complex: sativa-caerulea-falcata inferred
      from comparative cytogenetic analysis.
AB  - BACKGROUND: Polyploidy plays an important role in the adaptation and speciation
      of plants. The alteration of karyotype is a significant event during polyploidy
      formation. The Medicago sativa complex includes both diploid (2n = 2* = 16) and
      tetraploid (2n = 2* = 32) subspecies. The tetraploid M. ssp. sativa was regarded
      as having a simple autopolyploid origin from diploid ssp. caerulea, whereas the
      autopolyploid origin of tetraploid ssp. falcata from diploid form ssp. falcata is
      still in doubt. In this study, detailed comparative cytogenetic analysis between
      diploid to tetraploid species, as well as genomic affinity across different
      species in the M. sativa complex, were conducted based on comparative mapping of
      11 repeated DNA sequences and two rDNA sequences by a fluorescence in situ
      hybridization (FISH) technique. RESULTS: FISH patterns of the repeats in diploid
      subspecies caerulea were highly similar to those in tetraploid subspecies sativa.
      Distinctly different FISH patterns were first observed in diploid ssp. falcata,
      with only centromeric hybridizations using centromeric and multiple region
      repeats and a few subtelomeric hybridizations using subtelomeric repeats.
      Tetraploid subspecies falcata was unexpectedly found to possess a highly variable
      karyotype, which agreed with neither diploid ssp. falcata nor ssp. sativa.
      Reconstruction of chromosome-doubling process of diploid ssp. caerulea showed
      that chromosome changes have occurred during polyploidization process.
      CONCLUSIONS: The comparative cytogenetic results provide reliable evidence that
      diploid subspecies caerulea is the direct progenitor of tetraploid subspecies
      sativa. And autotetraploid ssp. sativa has been suggested to undergo a partial
      diploidization by the progressive accumulation of chromosome structural
      rearrangements during evolution. However, the tetraploid subspecies falcata is
      far from a simple autopolyploid from diploid subspecies falcata although no
      obvious morphological change was observed between these two subspecies.

PMID- 28427347
TI  - Comparative transcriptomics of mountain pine beetle pheromone-biosynthetic
      tissues and functional analysis of CYP6DE3.
AB  - BACKGROUND: The mountain pine beetle (MPB, Dendroctonus ponderosae Hopkins) is a
      highly destructive pest of pine forests in western North America. During flight
      to a new host tree and initiation of feeding, mountain pine beetles release
      aggregation pheromones. The biosynthetic pathways of these pheromones are sex
      specific and localized in the midgut and fat body, but the enzymes involved have
      not all been identified or characterized. RESULTS: We used a comparative RNA-Seq
      analysis between fed and unfed male and female MPB midguts and fat bodies to
      identify candidate genes involved in pheromone biosynthesis. The 13,407
      potentially unique transcripts showed clear separation based on feeding state and
      gender. Gene co-expression network construction and examination using petal
      identified gene groups that were tightly connected. This, as well as other co
      expression and gene ontology analyses, identified all four known pheromone
      biosynthetic genes, confirmed the tentative identification of four others from a
      previous study, and suggested nine novel candidates. One cytochrome P450
      monooxygenase, CYP6DE3, identified as a possible exo-brevicomin-biosynthetic
      enzyme in this study, was functionally characterized and likely is involved in
      resin detoxification rather than pheromone biosynthesis. CONCLUSIONS: Our
      analysis supported previously characterized pheromone-biosynthetic genes involved
      in exo-brevicomin and frontalin biosynthesis and identified a number of candidate
      cytochrome P450 monooxygenases and a putative cyclase for further studies.
      Functional analyses of CYP6DE3 suggest its role in resin detoxification and
      underscore the limitation of using high-throughput data to tentatively identify
      candidate genes. Further functional analyses of candidate genes found in this
      study should lead to the full characterization of MPB pheromone biosynthetic
      pathways and the identification of molecular targets for possible pest management
      strategies.

PMID- 28427348
TI  - Comparative genomics and evolution of the amylase-binding proteins of oral
      streptococci.
AB  - BACKGROUND: Successful commensal bacteria have evolved to maintain colonization
      in challenging environments. The oral viridans streptococci are pioneer
      colonizers of dental plaque biofilm. Some of these bacteria have adapted to life
      in the oral cavity by binding salivary alpha-amylase, which hydrolyzes dietary
      starch, thus providing a source of nutrition. Oral streptococcal species bind
      alpha-amylase by expressing a variety of amylase-binding proteins (ABPs). Here we
      determine the genotypic basis of amylase binding where proteins of diverse size
      and function share a common phenotype. RESULTS: ABPs were detected in culture
      supernatants of 27 of 59 strains representing 13 oral Streptococcus species
      screened using the amylase-ligand binding assay. N-terminal sequences from ABPs
      of diverse size were obtained from 18 strains representing six oral streptococcal
      species. Genome sequencing and BLAST searches using N-terminal sequences, protein
      size, and key words identified the gene associated with each ABP. Among the
      sequenced ABPs, 14 matched amylase-binding protein A (AbpA), 6 matched amylase
      binding protein B (AbpB), and 11 unique ABPs were identified as peptidoglycan
      binding, glutamine ABC-type transporter, hypothetical, or choline-binding
      proteins. Alignment and phylogenetic analyses performed to ascertain evolutionary
      relationships revealed that ABPs cluster into at least six distinct, unrelated
      families (AbpA, AbpB, and four novel ABPs) with no phylogenetic evidence that one
      group evolved from another, and no single ancestral gene found within each group.
      AbpA-like sequences can be divided into five subgroups based on the N-terminal
      sequences. Comparative genomics focusing on the abpA gene locus provides evidence
      of horizontal gene transfer. CONCLUSION: The acquisition of an ABP by oral
      streptococci provides an interesting example of adaptive evolution.

PMID- 28427349
TI  - Genome-wide survey of miRNAs and their evolutionary history in the ascidian,
      Halocynthia roretzi.
AB  - BACKGROUND: miRNAs play essential roles in the modulation of cellular functions
      via degradation and/or translation attenuation of target mRNAs. They have been
      surveyed in a single ascidian genus, Ciona. Recently, an annotated draft genome
      sequence for a distantly related ascidian, Halocynthia roretzi, has become
      available, but miRNAs in H. roretzi have not been previously studied. RESULTS: We
      report the prediction of 319 candidate H. roretzi miRNAs, obtained through three
      complementary methods. Experimental validation suggests that more than half of
      these candidate miRNAs are expressed during embryogenesis. The majority of
      predicted H. roretzi miRNAs appear specific to ascidians or tunicates, and only
      32 candidates, belonging to 25 families, are widely conserved across metazoans.
      CONCLUSION: Our study presents a comprehensive identification of candidate H.
      roretzi miRNAs. This resource will facilitate the study of the mechanisms for
      miRNA-controlled gene regulatory networks during ascidian development. Further,
      our analysis suggests that the majority of Halocynthia miRNAs are specific to
      ascidian or tunicates, with only a small number of widely conserved miRNAs. This
      result is consistent with the general notion that animal miRNAs are less
      conserved between taxa than plant ones.

PMID- 28427350
TI  - Evaluation of a modified version of the Posttraumatic Growth Inventory-Short
      Form.
AB  - BACKGROUND: Posttraumatic growth is the positive change resulting from traumatic
      experiences and is typically assessed with retrospective measures like the
      Posttraumatic Growth Inventory (PTGI). The PTGI was designed to include reference
      to a specific traumatic event, making it difficult to implement, without change,
      in prospective survey studies. Thus, a modified Posttraumatic Growth Inventory
      Short Form (PTGI-SF) was included in a large prospective study of current and
      former U.S. military personnel. The current study provides preliminary
      psychometric data for this modified measure and its ability to assess
      psychological well-being at a single time point. METHODS: The study population (N
      = 135,843) was randomly and equally split into exploratory and confirmatory
      samples that were proportionately balanced on trauma criterion. Exploratory
      factor analysis and confirmatory factor analysis (CFA) were performed to assess
      the psychometric validity of the modified measure. The final model was also
      assessed in a subset of the confirmatory sample with a history of trauma using
      CFA. RESULTS: Results supported a single-factor model with two additional
      correlations between items assessing spirituality and items assessing
      compassion/appreciation for others. This model also fits among the subset with a
      history of trauma. The resulting measure was strongly associated with social
      support and personal mastery. CONCLUSIONS: The modified PTGI-SF in this study
      captures psychological well-being in cross-sectional assessments, in addition to
      being able to measure posttraumatic growth with multiple assessments. Results
      indicate that the modified measure is represented by a single factor, but that
      items assessing spirituality and compassion/appreciation for others may be used
      alone to better capture these constructs.

PMID- 28427351
TI  - Proteinuria and baseline renal function predict mortality and renal outcomes
      after sirolimus therapy in liver transplantation recipients.
AB  - BACKGROUND: Chronic kidney disease is a significant complication after liver
      transplantation (LT), but the role of pre-existing renal insufficiency and
      proteinuria remains unclear among LT recipients receiving sirolimus. METHODS: We
      assessed the effects of proteinuria and baseline renal function on long-term
      renal and survival outcomes among 576 LT recipients who received SRL in a medical
      center between 2005 and 2014. Renal outcomes were the incidences of >50%
      reduction in their baseline estimated glomerular filtration rate and end stage
      kidney disease requiring renal replacement therapy. Proteinuria was identified
      using morning dipstick results (>=30 mg/dL) at baseline and within the first year
      after the initiation of SRL therapy. A Kaplan-Meier analysis was performed to
      estimate time to event. Factors associated with the outcomes were determined
      using the Cox proportional hazards model with a significance level set at P
      <0.05. RESULTS: During the study period, renal function deteriorated in 135
      (25.3%) patients and 68 (11.8%) patients died. Persistent and new onset
      proteinuria contributed to a high rate of mortality and the deterioration of
      renal function (both log-rank tests, P <0.0001). After adjustments, new onset
      proteinuria within the first year after the initiation of SRL therapy increased
      the risk of deteriorating renal function, regardless of baseline estimated
      glomerular filtration rate. Moreover, pre-existing (hazard ratio = 1.91; P
      <0.001) and new onset diabetes (hazard ratio = 2.34; P <0.0001) were
      significantly associated with new onset proteinuria among SRL users. CONCLUSIONS:
      These findings support the effective monitoring and early management of the
      predictable risks for proteinuria among new SRL users in order to delay the
      progression of renal disease.

PMID- 28427352
TI  - Point of sampling detection of Zika virus within a multiplexed kit capable of
      detecting dengue and chikungunya.
AB  - BACKGROUND: Zika, dengue, and chikungunya are three mosquito-borne viruses having
      overlapping transmission vectors. They cause diseases having similar symptoms in
      human patients, but requiring different immediate management steps. Therefore,
      rapid (< one hour) discrimination of these three viruses in patient samples and
      trapped mosquitoes is needed. The need for speed precludes any assay that
      requires complex up-front sample preparation, such as extraction of nucleic acids
      from the sample. Also precluded in robust point-of-sampling assays is downstream
      release of the amplicon mixture, as this risks contamination of future samples
      that will give false positives. METHODS: Procedures are reported that directly
      test urine and plasma (for patient diagnostics) or crushed mosquito carcasses
      (for environmental surveillance). Carcasses are captured on paper samples
      carrying quaternary ammonium groups (Q-paper), which may be directly introduced
      into the assay. To avoid the time and instrumentation requirements of PCR, the
      procedure uses loop-mediated isothermal amplification (LAMP). Downstream
      detection is done in sealed tubes, with dTTP-dUTP mixtures in the LAMP with a
      thermolabile uracil DNA glycosylase (UDG); this offers a second mechanism to
      prevent forward contamination. Reverse transcription LAMP (RT-LAMP) reagents are
      distributed dry without requiring a continuous chain of refrigeration. RESULTS:
      The tests detect viral RNA in unprocessed urine and other biological samples,
      distinguishing Zika, chikungunya, and dengue in urine and in mosquitoes infected
      with live Zika and chikungunya viruses. The limits of detection (LODs) are ~0.71
      pfu equivalent viral RNAs for Zika, ~1.22 pfu equivalent viral RNAs for dengue,
      and ~38 copies of chikungunya viral RNA. A handheld, battery-powered device with
      an orange filter was constructed to visualize the output. Preliminary data showed
      that this architecture, working with pre-prepared tubes holding lyophilized
      reagent/enzyme mixtures and shipped without a chain of refrigeration, also worked
      with human plasma samples to detect chikungunya and dengue in Pune, India.
      CONCLUSIONS: A kit, complete with a visualization device, is now available for
      point-of-sampling detection of Zika, chikungunya, and dengue. The assay output is
      read in ca. 30 min by visualizing (human eye) three-color coded fluorescence
      signals. Assay in dried format allows it to be run in low-resource environments.

PMID- 28427353
TI  - Assessing the impact of natural policy experiments on socioeconomic inequalities
      in health: how to apply commonly used quantitative analytical methods?
AB  - BACKGROUND: The scientific evidence-base for policies to tackle health
      inequalities is limited. Natural policy experiments (NPE) have drawn increasing
      attention as a means to evaluating the effects of policies on health. Several
      analytical methods can be used to evaluate the outcomes of NPEs in terms of
      average population health, but it is unclear whether they can also be used to
      assess the outcomes of NPEs in terms of health inequalities. The aim of this
      study therefore was to assess whether, and to demonstrate how, a number of
      commonly used analytical methods for the evaluation of NPEs can be applied to
      quantify the effect of policies on health inequalities. METHODS: We identified
      seven quantitative analytical methods for the evaluation of NPEs: regression
      adjustment, propensity score matching, difference-in-differences analysis, fixed
      effects analysis, instrumental variable analysis, regression discontinuity and
      interrupted time-series. We assessed whether these methods can be used to
      quantify the effect of policies on the magnitude of health inequalities either by
      conducting a stratified analysis or by including an interaction term, and
      illustrated both approaches in a fictitious numerical example. RESULTS: All seven
      methods can be used to quantify the equity impact of policies on absolute and
      relative inequalities in health by conducting an analysis stratified by
      socioeconomic position, and all but one (propensity score matching) can be used
      to quantify equity impacts by inclusion of an interaction term between
      socioeconomic position and policy exposure. CONCLUSION: Methods commonly used in
      economics and econometrics for the evaluation of NPEs can also be applied to
      assess the equity impact of policies, and our illustrations provide guidance on
      how to do this appropriately. The low external validity of results from
      instrumental variable analysis and regression discontinuity makes these methods
      less desirable for assessing policy effects on population-level health
      inequalities. Increased use of the methods in social epidemiology will help to
      build an evidence base to support policy making in the area of health
      inequalities.

PMID- 28427354
TI  - Unique case report of a chromomycosis and Listeria in soft tissue and cerebellar
      abscesses after kidney transplantation.
AB  - BACKGROUND: Chromomycosis is a rare mycotic infection encountered in tropical and
      subtropical regions. The disease presents as a slowly-evolving nodule that can
      become infected with bacteria. Here, we describe a unique association of
      abscesses caused by a chromomycosis and Listeria monocytogenes in a kidney
      transplant recipient, and didactically expose how the appropriate diagnosis was
      reached. CASE PRESENTATION: A 49-year old male originating from the Caribbean
      presented a scalp lesion which was surgically removed in his hometown where it
      was misdiagnosed as a sporotrichosis on histology, 3 years after he received a
      kidney transplant. He received no additional treatment and the scalp lesion
      healed. One year later, an abscess of each thigh due to both F. pedrosoi and L.
      monocytogenes was diagnosed in our institution. A contemporary asymptomatic
      cerebellar abscess was also found by systematic MRI. An association of
      amoxicillin and posaconazole allowed a complete cure of the patient without
      recurring to surgery. Histological slides from the scalp lesion were re-examined
      in our institution and we retrospectively concluded to a first localisation of
      the chromomycosis. We discuss the possible pathophysiology of this very unusual
      association. CONCLUSION: In this case of disseminated listeriosis and
      chromomycosis, complete cure of the patients could be reached with oral anti
      infectious treatment only.

PMID- 28427355
TI  - Identifying and characterizing hepatitis C virus hotspots in Massachusetts: a
      spatial epidemiological approach.
AB  - BACKGROUND: Hepatitis C virus (HCV) infections have increased during the past
      decade but little is known about geographic clustering patterns. METHODS: We used
      a unique analytical approach, combining geographic information systems (GIS),
      spatial epidemiology, and statistical modeling to identify and characterize HCV
      hotspots, statistically significant clusters of census tracts with elevated HCV
      counts and rates. We compiled sociodemographic and HCV surveillance data (n =
      99,780 cases) for Massachusetts census tracts (n = 1464) from 2002 to 2013. We
      used a five-step spatial epidemiological approach, calculating incremental
      spatial autocorrelations and Getis-Ord Gi* statistics to identify clusters. We
      conducted logistic regression analyses to determine factors associated with the
      HCV hotspots. RESULTS: We identified nine HCV clusters, with the largest in
      Boston, New Bedford/Fall River, Worcester, and Springfield (p < 0.05). In
      multivariable analyses, we found that HCV hotspots were independently and
      positively associated with the percent of the population that was Hispanic
      (adjusted odds ratio [AOR]: 1.07; 95% confidence interval [CI]: 1.04, 1.09) and
      the percent of households receiving food stamps (AOR: 1.83; 95% CI: 1.22, 2.74).
      HCV hotspots were independently and negatively associated with the percent of the
      population that were high school graduates or higher (AOR: 0.91; 95% CI: 0.89,
      0.93) and the percent of the population in the "other" race/ethnicity category
      (AOR: 0.88; 95% CI: 0.85, 0.91). CONCLUSION: We identified locations where HCV
      clusters were a concern, and where enhanced HCV prevention, treatment, and care
      can help combat the HCV epidemic in Massachusetts. GIS, spatial epidemiological
      and statistical analyses provided a rigorous approach to identify hotspot
      clusters of disease, which can inform public health policy and intervention
      targeting. Further studies that incorporate spatiotemporal cluster analyses,
      Bayesian spatial and geostatistical models, spatially weighted regression
      analyses, and assessment of associations between HCV clustering and the built
      environment are needed to expand upon our combined spatial epidemiological and
      statistical methods.

PMID- 28427356
TI  - Postural effects on intraocular pressure and ocular perfusion pressure in
      patients with non-arteritic anterior ischemic optic neuropathy.
AB  - BACKGROUND: To investigate postural effects on intraocular pressure (IOP) and
      ocular perfusion pressure (OPP) in patients with non-arteritic ischemic optic
      neuropathy (NAION). METHODS: IOP and blood pressure (BP) were measured in 20
      patients with unilateral NAION 10 min after changing to each of the following
      positions sequentially: sitting, supine, right lateral decubitus position (LDP),
      supine, left LDP, and supine. IOP was measured using a rebound tonometer and OPP
      was calculated using formulas based on mean BP. The dependent LDP (DLDP) was
      defined as the position when the eye of interest (affected or unaffected eye) was
      placed on the dependent side in the LDP. RESULTS: IOPs were significantly higher
      (P = 0.020) and OPPs were significantly lower (P = 0.041) in the affected eye
      compare with the unaffected eye, with the affected eye in DLDP. Compared with the
      mean IOP of the unaffected eyes, the mean IOP of the affected eyes increased
      significantly (+2.9 +/- 4.4 versus +0.7 +/- 3.1 mmHg, respectively; P = 0.003)
      and the mean OPP decreased significantly (-6.7 +/- 9.4 versus -4.9 +/- 8.0 mmHg,
      respectively; P = 0.022) after changing positions from supine to DLDP. In
      addition, changing position from supine to DLDP showed significantly larger
      absolute changes in IOP (4.13 +/- 3.19 mmHg versus 2.51 +/- 1.92 mmHg,
      respectively; P = 0.004) and OPP (9.86 +/- 5.69 mmHg versus 7.50 +/- 5.49 mmHg,
      respectively; P = 0.009) in the affected eye compared with the unaffected eye. In
      the affected eye, there was a significant positive correlation between absolute
      change in IOP and OPP when changing position from supine to DLDP (Rho = 0.512, P
      = 0.021). CONCLUSIONS: A postural change from supine to DLDP caused significant
      fluctuations in IOP and OPP of the affected eye, and may significantly increase
      IOP and decrease OPP. Posture-induced IOP changes may be a predisposing factor
      for NAION development.

PMID- 28427358
TI  - Cortical laminar necrosis in dengue encephalitis-a case report.
AB  - BACKGROUND: Dengue encephalitis is a rare neurological manifestation of dengue
      fever. Its clinical presentation is similar to other viral encephalitides and
      encephalopathy. No single specific finding on magnetic resonance imaging of
      dengue encephalitis has yet been documented. They are highly variable and
      atypical. CASE PRESENTATION: A 15-year boy presented with fever, the headache and
      altered sensorium of 12-day duration. On neurological examination, his Glasgow
      Coma Scale score was 10 (E3M4V3). There was no focal neurological deficit.
      Laboratory evaluation revealed leukopenia and marked thrombocytopenia. Dengue
      virus IgM antibody was positive both in serum and cerebrospinal fluid. Magnetic
      resonance imaging of the brain revealed signal changes in bilateral
      parietooccipital and left frontal regions (left hemisphere more involved than the
      right hemisphere). There was gyriform enhancement bilateral parietooccipital
      regions consistent with cortical laminar necrosis. Bilaterally diffuse
      subcortical white matter was also involved and subtle T2 hyperintensity involving
      both basal ganglia was noted. Gradient echo sequence revealed presence of
      hemorrhage in the subcortical white matter. Patient was treated conservatively
      and received platelet transfusion. Patient became fully conscious after 7 days.
      CONCLUSION: In a patient with highly suggestive dengue e?ephalitis, we describe
      an unusual magnetic resonance imaging finding. This report is possibly the first
      instance of cortical laminar necrosis in such a setting.

PMID- 28427357
TI  - Haplotype of non-synonymous mutations within IL-23R is associated with
      susceptibility to severe malaria anemia in a P. falciparum holoendemic
      transmission area of Kenya.
AB  - BACKGROUND: Improved understanding of the molecular mechanisms involved in
      pediatric severe malarial anemia (SMA) pathogenesis is a crucial step in the
      design of novel therapeutics. Identification of host genetic susceptibility
      factors in immune regulatory genes offers an important tool for deciphering
      malaria pathogenesis. The IL-23/IL-17 immune pathway is important for both
      immunity and erythropoiesis via its effects through IL-23 receptors (IL-23R).
      However, the impact of IL-23R variants on SMA has not been fully elucidated.
      METHODS: Since variation within the coding region of IL-23R may influence the
      pathogenesis of SMA, the association between IL-23R rs1884444 (G/T), rs7530511
      (C/T), and SMA (Hb < 6.0 g/dL) was examined in children (n = 369, aged 6-36
      months) with P. falciparum malaria in a holoendemic P. falciparum transmission
      area. RESULTS: Logistic regression analysis, controlling for confounding factor
      of anemia, revealed that individual genotypes of IL-23R rs1884444 (G/T) [GT; OR =
      1.34, 95% CI = 0.78-2.31, P = 0.304 and TT; OR = 2.02, 95% CI = 0.53-7.74, P =
      0.286] and IL-23R rs7530511 (C/T) [CT; OR = 2.6, 95% CI = 0.59-11.86, P = 0.202
      and TT; OR = 1.66, 95% CI = 0.84-3.27, P = 0.142] were not associated with
      susceptibility to SMA. However, carriage of IL-23R rs1884444T/rs7530511T (TT)
      haplotype, consisting of both mutant alleles, was associated with increased
      susceptibility to SMA (OR = 1.12, 95% CI = 1.07-4.19, P = 0.030). CONCLUSION:
      Results presented here demonstrate that a haplotype of non-synonymous IL-23R
      variants increase susceptibility to SMA in children of a holoendemic P.
      falciparum transmission area.

PMID- 28427359
TI  - Neo-Marxian social class inequalities in self-rated health among the employed in
      South Korea: the role of material, behavioral, psychosocial, and workplace
      environmental factors.
AB  - BACKGROUND: The aim of this study was to examine the pattern of social inequality
      in self-rated health among the employed using the Wright's social class location
      indicator, and to assess the roles of material, behavioral, psychosocial, and
      workplace environmental factors as mediating factors in explaining the social
      class inequality in self-rated health in South Korea. METHODS: This study used
      data from the 4th Korea National Health and Nutrition Examination Survey from
      2007 to 2009. Study subjects included the employed population of 4392 men and
      3309 women aged 19-64 years. Subjects were classified into twelve social class
      positions based on the Wright's social class map. The health outcome was self
      rated health. Material, psychosocial, behavioral, and workplace environmental
      factors were considered as potential mediators in explaining social class health
      inequality. We calculated prevalence ratios of poor self-rated health according
      to social class, adjusted for age and mediating factors using Poisson regression
      models. RESULTS: Nonskilled workers and petty bourgeoisie reported worse self
      rated health than other social classes among men. The age-adjusted prevalence of
      petty bourgeoisie and nonskilled workers were about four-fold greater than that
      of managers. Expert supervisors in the contradictory class location had a greater
      prevalence of poor self-rated health than experts in men. In women, the
      prevalence of poor self-rated health was greater in most social classes than
      their male counterparts, while the differences among social classes within women
      were not statistically significant. Workplace environmental factors explained the
      social class inequality by from 24 to 31% in nonskilled and skilled workers and
      nonskilled supervisors, respectively, and material factors showed an explanatory
      ability of about 8% for both nonskilled workers and petty bourgeoisie in men.
      CONCLUSIONS: We showed the inequality in self-rated health according to the
      Wright's social class in an industrialized Asian country. Policy efforts to
      improve workplace environments in nonskilled and skilled workers and nonskilled
      supervisors would have a moderate effect on reducing the magnitude of social
      class inequality in self-rated health. Furthermore, the means to improve power
      relations in the workplace should be devised to further reduce the social class
      inequalities in health.

PMID- 28427360
TI  - Association of novel polymorphisms in TMEM39A gene with systemic lupus
      erythematosus in a Chinese Han population.
AB  - BACKGROUND: This study aimed to assess the association between 14 single
      nucleotide polymorphisms (SNPs) in six genes (IRF8, TMEM39A, IKZF3, ORMDL3,
      GSDMB, and ZPBP2) and systemic lupus erythematosus (SLE) in a Chinese Han
      population sample. METHODS: We carried out a case-control study of 415 patients
      with SLE and 470 healthy controls without autoimmune disease or cancer. DNA for
      genetic analysis was isolated from the blood of all subjects using standard
      phenol-chloroform method. TagSNPs were identified using genotype data from the
      panel (Han Chinese in Beijing) of the HapMap Project and were selected using the
      Haploview program. Genotyping assay was conducted using the Sequenom MassARRAY
      iPLEX Gold platform. The frequencies of the alleles and genotypes were calculated
      and analyzed. Association studies and haplotype analysis were also performed.
      RESULTS: The genotypic frequencies of rs12493175 and rs13062955 were
      significantly different between the SLE patients and the healthy controls.
      Compared with the common homozygous genotype, the CT and CT + TT genotypes in
      rs12493175 and the AC and AC + AA genotypes in rs13062955 was observed to
      significantly reduce the risk of SLE. The haplotype analysis of TMEM39A
      polymorphisms showed that the CGTA haplotype frequency was significantly low in
      the SLE patients. CONCLUSION: Our findings identified three novel associations in
      SNPs located in the TMEM39A gene associated with SLE susceptibility in a Chinese
      Han population.

PMID- 28427361
TI  - Lifestyle-related factors that explain disaster-induced changes in socioeconomic
      status and poor subjective health: a cross-sectional study from the Fukushima
      health management survey.
AB  - BACKGROUND: Socioeconomic status (SES) and lifestyle-related factors are
      determinants of subjective health. However, changes in SES are inevitable in
      times of natural disaster, while lifestyle-related factors remain modifiable. The
      aim of this study was to use a cross-sectional approach to examine lifestyle
      related factors that may attenuate the negative impact of disaster-induced
      changes in SES on poor subjective health. METHODS: We analyzed 33,350 men and
      women aged 20-64 years who were living in evacuation zones due to the radiation
      accident in Fukushima, Japan. Disaster-induced changes in SES were defined by
      living arrangements and working conditions. Using Poisson regression analysis
      adjusted for confounders (model 1) and lifestyle-related factors as intermediate
      variables (model 2), we compared the prevalence ratios (PRs) of poor subjective
      health of participants who did not undergo disaster-induced changes in SES (did
      not become unemployed, income did not decrease, and living in relative's home/own
      home) with that of participants who did undergo disaster-induced changes in SES
      (became unemployed, decreased income, or lived in an evacuation shelter,
      temporary housing, or rental housing/apartment). We calculated the percentage of
      excess risks explained by lifestyle-related factors as follows: ((PRmodel 1 -
      PRmodel 2)/(PRmodel 1-1)) * 100. RESULTS: Disaster-induced changes in SES were
      significantly associated with poor subjective health. The PRs (95% CIs) among
      participants who underwent disaster-induced changes in SES were 2.02 (1.81-2.24)
      for men and 1.80 (1.65-1.97) for women. After adjusting for lifestyle-related
      factors, we found that the PRs in men and women were remarkably attenuated,
      decreasing to 1.56 (1.40-1.73) and 1.43 (1.31-1.55), respectively. Controlling
      for lifestyle-related factors resulted in PR attenuation by 45.1% (men) and 46.3%
      (women). Satisfaction of sleep and participation in recreation and community
      activity particularly contributed to this attenuation. CONCLUSIONS: While
      disaster-induced changes in SES are unavoidable, lifestyle-related factors have
      the potential to attenuate the impact of these changes on poor subjective health.

PMID- 28427362
TI  - Efficacy of budesonide/formoterol maintenance and reliever therapy compared with
      higher-dose budesonide as step-up from low-dose inhaled corticosteroid treatment.
AB  - BACKGROUND: Asthma management may involve a step up in treatment when symptoms
      are not well controlled. We examined whether budesonide/formoterol maintenance
      and reliever therapy (MRT) is as effective as higher, fixed-dose budesonide plus
      as-needed terbutaline in patients requiring step-up from Step 2 treatment (low
      dose inhaled corticosteroids), stratified by baseline reliever use. METHODS: A
      post-hoc analysis utilized data from three clinical trials of 6-12 months'
      duration. Patients aged >=12 years with symptomatic asthma uncontrolled despite
      Step 2 treatment were included. Severe exacerbation rate, lung function and
      reliever use were analysed, stratified by baseline reliever use (<1, 1-2 and >2
      occasions/day). RESULTS: Overall, 1239 patients were included. Reductions in
      severe exacerbation rate with budesonide/formoterol MRT versus fixed-dose
      budesonide were similar across baseline reliever use levels, and were
      statistically significant in patients using 1-2 (42%, p = 0.01) and >2 (39%, p =
      0.02) reliever occasions/day, but not <1 reliever occasion/day (35%, p = 0.11).
      Both treatments significantly increased mean FEV1 from baseline; improvements
      were significantly greater for budesonide/formoterol MRT in all reliever use
      groups. Reductions in reliever use from baseline were significantly greater with
      budesonide/formoterol MRT versus fixed-dose budesonide in patients using 1-2 and
      >2 reliever occasions/day (-0.33 and -0.74 occasions/day, respectively).
      CONCLUSIONS: Treatment benefit with budesonide/formoterol MRT versus higher,
      fixed-dose budesonide plus short-acting beta2-agonist was found in Step 2
      patients with relatively low reliever use, supporting the proposal that
      budesonide/formoterol MRT may be useful when asthma is uncontrolled with low-dose
      inhaled corticosteroid.

PMID- 28427363
TI  - A spatio-temporal analysis of suicide in El Salvador.
AB  - BACKGROUND: In 2012, international statistics showed El Salvador's suicide rate
      as 40th in the world and the highest in Latin America. Over the last 15 years,
      national statistics show the suicide death rate declining as opposed to an
      increasing rate of homicide. Though completed suicide is an important social and
      health issue, little is known about its prevalence, incidence, etiology and
      spatio-temporal behavior. The primary objective of this study was to examine
      completed suicide and homicide using the stream analogy to lethal violence within
      a spatio-temporal framework. METHODS: A Bayesian model was applied to examine the
      spatio-temporal evolution of the tendency of completed suicide over homicide in
      El Salvador. Data on numbers of suicides and homicides at the municipal level
      were obtained from the Instituto de Medicina Legal (IML) and population counts,
      from the Direccion General de Estadistica y Censos (DIGESTYC), for the period of
      2002 to 2012. Data on migration were derived from the 2007 Population Census, and
      inequality data were obtained from a study by Damianovic, Valenzuela and Vera.
      RESULTS: The data reveal a stable standardized rate of total lethal violence
      (completed suicide plus homicide) across municipalities over time; a decline in
      suicide; and a standardized suicide rate decreasing with income inequality but
      increasing with social isolation. Municipalities clustered in terms of both total
      lethal violence and suicide standardized rates. CONCLUSIONS: Spatial effects for
      suicide were stronger among municipalities located in the north-east and center
      south sides of the country. New clusters of municipalities with large suicide
      standardized rates were detected in the north-west, south-west and center-south
      regions, all of which are part of time-stable clusters of homicide. Prevention
      efforts to reduce income inequality and mitigate the negative effects of weak
      relational systems should focus upon municipalities forming time-persistent
      clusters with a large rate of death by suicide. In municipalities that are part
      of newly-formed suicide clusters and also are located in areas with a large rate
      of homicide, interrupting the expansion of spatial concentrations of suicide over
      time may require the implementation of both public health and public safety
      interventions.

PMID- 28427364
TI  - National Alcohol Survey of households in Trinidad and Tobago (NASHTT): Alcohol
      use in households.
AB  - BACKGROUND: To determine the patterns of alcohol use among households in Trinidad
      and Tobago (T&T) and to estimate the association between alcohol use and negative
      psychological, social, or physical events experienced by the household. METHODS:
      A convenience sample of 1837 households across T&T. We identified bivariate
      correlates of alcohol use, and heavy episodic drinking using chi-square and t
      test analyses and used multivariable logistic regression to estimate adjusted
      associations between household alcohol use and experiences within the past 12
      months adjusted for sociodemographic covariates. RESULTS: One thousand five
      hundred two households had complete data for all variables (82% response rate).
      Nearly two thirds (64%) of households included alcohol users; 57% of household
      that consumed alcohol also reported heavy episodic drinking. Households that
      reported alcohol consumption were significantly more likely to report illnesses
      within the households, relationship problems, and behavioral and antisocial
      problems with children. Among households where a member was employed, those who
      consumed alcohol were nearly twice as likely (OR = 1.98; 95% confidence interval
      (CI) 1.03, 3.82) to have a household member call in sick to work and 2.9 times as
      likely (OR = 2.9; CI 1.19, 7.04) to have a household member suffer work related
      problems compared with households who reported not consuming alcohol.
      CONCLUSIONS: Approximately two thirds of households in T&T reported using
      alcohol. These households were more likely to report psychological, physical, and
      social problems. These findings would support efforts to enforce current
      policies, laws, and regulations as well as new strategies to reduce the impact of
      harmful alcohol consumption on households in T&T.

PMID- 28427365
TI  - Association between Fcgamma receptor IIA, IIIA and IIIB genetic polymorphisms and
      susceptibility to severe malaria anemia in children in western Kenya.
AB  - BACKGROUND: Naturally-acquired immunity to Plasmodium falciparum malaria develops
      after several episodes of infection. Fc gamma receptors (FcgammaRs) bind to
      immunoglobulin G (IgG) antibodies and mediate phagocytosis of opsonized microbes,
      thereby, linking humoral and cellular immunity. FcgammaR polymorphisms influence
      binding affinity to IgGs and consequently, can influence clinical malaria
      outcomes. Specifically, variations in FcgammaRIIA -131Arg/His, FcgammaRIIIA
      176F/V and FcgammaRIIIB-NA1/NA2 modulate immune responses through altered binding
      preferences to IgGs and immune complexes. Differential binding, in turn, changes
      ability of immune cells to respond to infection through production of
      inflammatory mediators during P. falciparum infection. METHODS: We determined the
      association between haplotypes of FcgammaRIIA-131Arg/His, FcgammaRIIIA-176F/V and
      FcgammaRIIIB-NA1/NA2 variants and severe malarial anemia (SMA; hemoglobin < 6.0
      g/dL, any density parasitemia) in children (n = 274; aged 6-36 months) presenting
      for their first hospital visit with P. falciparum malaria in a holoendemic
      transmission region of western Kenya. FcgammaRIIA-131Arg/His and FcgammaRIIIA
      176F/V genotypes were determined using TaqMan(r) SNP genotyping, while
      FcgammaRIIIBNA1/NA2 genotypes were determined using restriction fragment length
      polymorphism. Hematological and parasitological indices were measured in all
      study participants. RESULTS: Carriage of FcgammaRIIA-131Arg/FcgammaRIIIA
      176F/FcgammaRIIIBNA2 haplotype was associated with susceptibility to SMA (OR =
      1.70; 95% CI; 1.02-2.93; P = 0.036), while the FcgammaRIIA-131His/ FcgammaRIIIA
      176F/ FcgammaRIIIB NA1 haplotype was marginally associated with enhanced
      susceptibility to SMA (OR: 1.80, 95% CI; 0.98-3.30, P = 0.057) and higher levels
      of parasitemia (P = 0.009). Individual genotypes of FcgammaRIIA-131Arg/His,
      FcgammaRIIIA-176F/V and FcgammaRIIIB-NA1/NA2 were not associated with
      susceptibility to SMA. CONCLUSION: The study revealed that haplotypes of
      FcgammaRs are important in conditioning susceptibility to SMA in immune-naive
      children from P. falciparum holoendemic region of western Kenya.

PMID- 28427366
TI  - Network analysis of global tobacco control collaboration: data from the World
      Conference on Tobacco or Health (WCTOH).
AB  - BACKGROUND: The World Conference on Tobacco or Health (WCTOH) is held every three
      years to foster communication and collaboration on global tobacco control. Very
      little is known about the nature of interactions between WCTOH attendees and
      their linkages to tobacco control organizations, so knowing this information
      could help improve tobacco control efforts. METHODS: At the 2015 WCTOH, we
      implemented an online survey to assess barriers to global tobacco control
      activities, which information sources they use for tobacco control information,
      and with whom they interact regarding tobacco control. RESULTS: A total of 169
      respondents completed the survey, with responses from all six World Health
      Organization (WHO) regions. Respondents worked in all areas of tobacco control;
      the most common were research (29.2%) and patient care/treatment (23.3%). The top
      barriers faced regarding tobacco control activities were: funding is weak
      (56.8%), government commitment (45.0%), tobacco industry interference (43.8%),
      and lack of coordination (34.3%). The network analysis identified Framework
      Convention Alliance (FCA) and Society for Research on Nicotine and Tobacco (SRNT)
      as the two most prominent groups that people belonged to and where they went to
      exchange information and best practices. Important regional and country specific
      groups also appear to be growing, such as the African Tobacco Control Alliance
      (ATCA) and the Argentinian Association of Tabacology (ASAT). DISCUSSION: Mapping
      and better understanding the global tobacco control network is important for
      informing knowledge exchange and best practices, particularly as increasing
      attention is being focused on global tobacco control efforts in low- and middle
      income countries in particular. CONCLUSIONS: The present study demonstrates that
      even a subsample of the WCTOH shows considerable collaboration. The full WCTOH
      network should be mapped in order to foster greater collaboration that has the
      the potential to improve global tobacco control efforts.

PMID- 28427367
TI  - Determinants of delayed care seeking for TB suggestive symptoms in Seru district,
      Oromiya region, Ethiopia: a community based unmatched case-control study.
AB  - BACKGROUND: Early tuberculosis (TB) case finding and adequate chemotherapy are
      essential for interrupting disease transmission and preventing complications due
      to delayed care seeking. This study was undertaken in order to provide insights
      into the magnitude and determinants of patient delay. METHODS: The study was
      conducted in rural Seru district, employing a population based unmatched case
      control study design. The WHO standardized TB screening tool was used to identify
      presumptive TB cases among the district population ages > 15 years. Presumptive
      TB cases who sought care in a health facility more than 14 days after the onset
      of symptoms were considered cases while those who sought care within the first 14
      days were classified as controls. A structured interview questionnaire was used
      to capture socio demographic characteristics and health care service utilization
      related data from the study participants. A multiple binary logistic regression
      model was used to identify any factor associated with patient care seeking delay.
      RESULT: A total of 9,782 individuals were screened, of which 980 (10%, 95% CI;
      9.4-10.5%) presumptive TB cases were identified. From these cases 358 (76%, 95%
      CI; 75.6%-76.4%) sought care within the first 14 days of the onset of symptoms
      with a median patient delay of 15 days, IQR (5-30 days). The most common TB
      suggestive symptom mentioned by the participants was night sweat 754 (76.4%)
      while the least common was a history of contact with a confirmed TB case in the
      past one year 207 (21.1%). Individuals in the 45-54 age range had lower odds of
      delay (AOR 0.31, 95%CI 0.15, 0.61) as compared to those 15-24 years old. First TB
      treatment episode (AOR16.2, 95% CI 9.94, 26.26) and limited access to either
      traditional or modern modes of transportation (AOR 2.62, 95% CI 1.25, 5.49) were
      independently associated with patient care delay. CONCLUSION: Increasing
      community awareness about the risks of delayed care seeking and the importance of
      accessing health services close to the community can help decrease patient care
      delay.

PMID- 28427368
TI  - Complications of miliary tuberculosis: low mortality and predictive biomarkers
      from a UK cohort.
AB  - BACKGROUND: Untreated, miliary tuberculosis (TB) has a mortality approaching
      100%. As it is uncommon there is little specific data to guide its management. We
      report detailed data from a UK cohort of patients with miliary tuberculosis and
      the associations and predictive ability of admission blood tests with clinical
      outcomes. METHODS: Routinely collected demographic, clinical, blood, imaging,
      histopathological and microbiological data were assessed for all patients with
      miliary TB identified from the London TB register from 2008 to 2012 from
      Northwest London Hospitals NHS Trust. Multivariable logistic regression was used
      to assess factors independently associated with the need for critical care
      intervention. Receiver operator characteristics (ROC) were calculated to assess
      the discriminatory ability of admission blood tests to predict clinical outcomes.
      RESULTS: Fifty-two patients were identified with miliary tuberculosis, of whom
      29% had confirmed central nervous system (CNS) involvement. Magnetic resonance
      imaging (MRI) was more sensitive than computed tomography (CT) or lumbar puncture
      for detecting CNS disease. Severe complications were frequent, with 15% requiring
      critical care intervention with mechanical ventilation. This was independently
      associated with admission hyponatraemia and elevated alanine aminotransferase
      (ALT). Having an admission sodium >=125 mmol/L and an ALT <180 IU/L had 82%
      sensitivity and 100% specificity for predicting a favourable outcome with an area
      under the ROC curve (AUC) of 0.91. Despite the frequency of severe complications,
      one-year mortality was low at 2%. CONCLUSIONS: Although severe complications of
      miliary tuberculosis were frequent, mortality was low with timely access to
      critical care intervention, anti-tuberculous therapy and possibly corticosteroid
      use. Clinical outcomes could accurately be predicted using routinely collected
      biochemistry data.

PMID- 28427369
TI  - Suicidal ideation and its correlates among high school students in Iran: a cross
      sectional study.
AB  - BACKGROUND: Globally, the second leading cause of death among adolescents is
      suicide and in middle-income countries adolescents' suicidal ideation is a
      neglected public health area. The present study was conducted to determine the
      prevalence and correlates of suicidal ideation among 15-17-year-old high school
      students in Iran. METHODS: Self-administered, Global School-based Student Health
      Survey (GSHS) questionnaires were distributed to a representative sample (N
      =1517) of high-school students aged 15-17 in the city of Tabriz. Multivariate
      logistic regression was used to assess the association between relevant
      independent variables (e.g. gender) and the dependent outcome variable (suicidal
      ideation in the past 12 months). RESULTS: Overall, 62 (4.1%, 95% CI= 3.1, 5.2) of
      1,517 students had thoughts of suicide. Three hundred and thirteen (20.6%, 95%
      CI= 18.6, 22.7) students reported being bullied in the previous 30 days. In
      addition, 134 (8.8%, 95% CI= 7.5, 10.3) students reported having been sexually
      abused. Being worried that they could not eat or did not feel hungry (Adjusted
      Odds Ratio (AOR) = 4.15; 95% Cl [1.71, 10.07]; current cigarette smoking (AOR =
      3.00; 95% CI [1.69, 5.30]; thinking about using alcohol or other drugs (AOR =
      4.28; 95% CI [2.41, 7.59]; and being sexually abused (AOR = 2.63; 95% CI [1.32,
      5.24]) were all factors positively associated with suicidal ideation. CONCLUSION:
      The prevalence of suicidal ideation was lower in our school students than in
      earlier studies. Interventions that address the issue of current cigarette
      smoking, worries, thinking about using alcohol or other drugs and sexual abuse
      should be given more priority by the public health authorities.

PMID- 28427370
TI  - Child sex tourism - prevalence of and risk factors for its use in a German
      community sample.
AB  - BACKGROUND: To investigate the prevalence of child sex tourism (CST) in a large
      German community sample, and to compare those who made use of CST with other
      child sexual abusers regarding established characteristics and risk factors for
      child sexual abuse. METHODS: Adult German men were recruited through a German
      market research panel and questioned by means of an anonymous online survey.
      Group assignment was accomplished based on information on previous sexual
      contacts with children and previous use of CST. Characteristics and risk factors
      were compared between the groups using t- and Chi-square tests. Binary logistic
      regression analysis was performed to predict CST. Data collection was conducted
      in 2013, data analysis in January 2015. RESULTS: Out of 8718 men, 36 (0.4%)
      reported CST use. The CST group differed from the nonCST group (n = 96; 1.1%)
      with regard to pedophilic sexual and antisocial behaviors as well as own
      experiences of sexual abuse. Social difficulties, pedophilic sexual interests,
      and hypersexuality were not distinct features in the CST group. Own experiences
      of sexual abuse, child prostitution use, and previous conviction for a violent
      offense predicted CST in a logistic regression model. CONCLUSIONS: This study is
      a first step to gain insight into the prevalence and characteristics of men using
      CST. Findings could help to augment prevention strategies against commercial
      forms of sexual abuse in developed as well as in developing countries by
      fostering the knowledge about the characteristics of perpetrators.

PMID- 28427371
TI  - Inside the nation's largest mental health institution: a prevalence study in a
      state prison system.
AB  - BACKGROUND: The United States has the highest incarceration rate in the world
      which has created a public health crisis. Correctional facilities have become a
      front line for mental health care. Public health research in this setting could
      inform criminal justice reform. We determined prevalence rates for mental
      illnesses and related comorbidities among all inmates in a state prison system.
      METHODS: Cross-sectional study using the Iowa Corrections Offender Network which
      contains health records of all inmates in Iowa. The point prevalence of both ICD
      9 and DSM-IV codes for mental illnesses, timing of diagnosis and interval between
      incarceration and mental illness diagnosis were determined. RESULTS: The average
      inmate (N = 8574) age was 36.7 +/- 12.4 years; 17% were >=50 years. The majority
      of inmates were men (91%) and white (65%).Obesity was prevalent in 38% of
      inmates, and 51% had a history of smoking. Almost half of inmates were diagnosed
      with a mental illness (48%), of whom, 29% had a serious mental illness (41% of
      all females and 27% of all males), and 26% had a history of a substance use
      disorder. Females had higher odds of having both a mental illness and substance
      use disorder. Almost all mental illness diagnoses were first made during
      incarceration (99%). The mean interval to diagnosis of depression, anxiety, PTSD
      and personality disorders were 26, 24, 21 and 29 months respectively. Almost 90%
      of mental illnesses were recognized by the 6th year of incarceration. The mean
      interval from incarceration to first diagnosis (recognition) of a substance abuse
      history was 11 months. CONCLUSIONS: There is a substantial burden of mental
      illness among inmates. Racial, age and gender disparities in mental health care
      are coupled with a general delay in diagnosis and treatment. A large part of
      understanding the mental health problem in this country starts at prisons.

PMID- 28427372
TI  - Protocol for evaluation of the continuum of primary care in the case of a
      miscarriage in the emergency room: a mixed-method study.
AB  - BACKGROUND: In Quebec (Canada), nearly 20,000 pregnancies end in miscarriage, and
      the majority of the miscarriages are dealt with in an emergency unit. Although
      there are studies documenting the effects of this type of grief on mental health,
      men's experiences are much less discussed than those of women. Similarly, no
      study has evaluated best practices in terms of service continuity, from emergency
      care to community resources. The aim of this study is to better understand the
      relationships that exist between the organization of emergency room and primary
      care health services for women presenting with miscarriage, on the one hand, and
      the positions and experiences of women and men within these services, on the
      other. METHODS: The general objective of this mixed-method study can be broken
      down into three methodological sections. Focus 1. Institutional discourses and
      practices. This section is structured as a multiple case study of the mandates of
      five participant institutions. The study will involve (a) a documentary analysis;
      (b) a quantitative survey (N: 200) and (c) group interviews (N: 75) with
      caregivers and emergency unit managers. Focus 2. Women's and men's experiences of
      miscarriages and the institutional response. This section includes (a) a survey
      (N: 232) and (b) individual interviews (N: 80) designed to identify best
      practices in emergency involving women and their partners in each area. Focus 3.
      This section will integrate the information furnished by the first two sections
      in order to create an ethnographic overview of the situation. DISCUSSION: This
      innovative project will provide answers to critical questions on how to improve
      the effectiveness and quality of interdisciplinary and multisectoral
      interventions to promote the mental health and psychosocial well-being of couples
      having experienced a miscarriage. It will have a material effect on the
      organization of emergency services and of the primary care pathway for women
      experiencing a miscarriage and for their partners. TRIAL REGISTRATION: Not
      applicable. This study involves a retrospective view of usual health care
      interventions. This study is not a clinical trial that prospectively assigns
      human participants or groups of humans to one or more health-related
      interventions to evaluate the effects on health outcomes.

PMID- 28427373
TI  - A protocol for a cluster-randomized controlled trial of a self-help psycho
      education programme to reduce diagnosis delay in women with breast cancer
      symptoms in Indonesia.
AB  - BACKGROUND: Breast cancer (BC) is the most frequent cancer occurring in women
      across the world. Its mortality rate in low-middle income countries (LMICs) is
      higher than in high-income countries (HICs), and in Indonesia BC is the leading
      cause of cancer deaths among women. Delay in breast cancer diagnosis negatively
      impacts cancer prognosis. Only about 30% of patients who come to the hospital to
      check on their breast abnormalities, continue thorough examination to biopsy to
      get a diagnosis based on the results of anatomical pathology. Many Indonesian
      women with breast cancer were already in an advanced stage when starting
      treatment. Therefore, delay in diagnosis is a serious problem that needs to be
      addressed. The present study will investigate whether our newly developed self
      help psycho-educational programme, "PERANTARA", for women with breast cancer
      symptoms is effective to reduce patient diagnosis delay in Indonesia. METHODS: A
      cluster-randomized controlled trial will be conducted in 106 patients in four
      hospitals in Bandung, West Java, Indonesia. Data will be collected at baseline
      (pre-assessment), 7 days after the intervention (post-assessment), and at 3
      months (follow-up assessments). The primary outcome is delay in diagnosis and
      treatment. Secondary outcomes are breast cancer knowledge, anxiety and
      depression, and quality of life. Exploratively, adherence with treatment will be
      measured too. Data will be analysed by hierarchical linear modelling (HLM) to
      assess differential change over time. DISCUSSION: If proven effective, PERANTARA
      will be evaluated and implemented in a diversity of settings for local cares
      (such as in POSYANDU, PUSKESMAS) that provide health education/psycho-education
      for women with breast symptoms. TRIAL REGISTRATION: ISRCTN12570738 . Date:
      November 19th, 2016.

PMID- 28427374
TI  - Prenatal determinants of physical activity and cardiorespiratory fitness in
      adolescence - Northern Finland Birth Cohort 1986 study.
AB  - BACKGROUND: Lower levels of physical activity and cardiorespiratory fitness are
      key risk factors of chronic adult diseases. Physical activity and
      cardiorespiratory fitness are predicted by birth weight, but the underlying
      parental and pregnancy-related factors remain largely unknown. We examined how
      prenatal determinants are associated with physical activity and cardiorespiratory
      fitness in adolescence. METHODS: Of the 16-year-old members of the population
      based Northern Finland Birth Cohort 1986 (NFBC 1986), 6682 singletons with no
      major physical disability reported their amount of physical activity outside
      school hours, and 4706 completed a submaximal cycle ergometer test assessing
      cardiorespiratory fitness. Physical activity was expressed as metabolic
      equivalent hours per week (METh/week) and cardiorespiratory fitness as peak
      oxygen uptake (ml.kg-1.min-1). Prenatal determinants included birth weight,
      length of gestation, mother's and father's body mass index (BMI), maternal
      gestational diabetes mellitus (GDM), and maternal hypertension and smoking during
      pregnancy. Data were analyzed by multiple linear regression. RESULTS: A higher
      birth weight and longer length of gestation predicted lower levels of physical
      activity and cardiorespiratory fitness at 16 years, although the association
      between length of gestation and physical activity was inverse U-shaped. Mother's
      or father's overweight or obesity before pregnancy were associated with lower
      levels of their offspring's physical activity and fitness in adolescence.
      Adjusting for maternal pregnancy disorders and the adolescent's own BMI
      attenuated the associations with the mother's but not the father's
      overweight/obesity. Furthermore, maternal GDM predicted lower cardiorespiratory
      fitness. CONCLUSIONS: A high birth weight and parental overweight/obesity are
      associated with lower levels of both physical activity and cardiorespiratory
      fitness in adolescence, while maternal GDM and longer length of gestation are
      associated with lower cardiorespiratory fitness. Both long and short lengths of
      gestation predict low physical activity.

PMID- 28427375
TI  - Relation between metabolic syndrome and body compositions among Chinese
      adolescents and adults from a large-scale population survey.
AB  - BACKGROUND: Few nationally representative surveys regarding body composition and
      metabolic syndrome (MetS) have been done in a large-scale representative Chinese
      population to explore the prediction of body composition indicators for MetS. The
      objective of this study was to examine the relation of body composition and MetS
      and to determine the optimal cut-off values of body composition indicators that
      predict MetS in a large representative Chinese sample based on multiple provinces
      and ethnicities, covering a broad age range from 10 to 80 years old. METHODS: The
      subjects came from a large-scale population survey on Chinese physiological
      constants and health conditions conducted in six provinces. 32,036 subjects
      completed all blood biochemical testing and body composition measure. Subjects
      meeting at least 3 of the following 5 criteria qualify as having MetS: elevated
      blood pressure, lower high density lipoprotein cholesterol level, higher
      triglyceride level, higher fasting glucose level and abdominal obesity. RESULTS:
      The total prevalence rate of MetS for males (9.29%) was lower than for females
      (11.58%). The prevalence rates were 12.03% for male adults and 15.57% for female
      adults respectively. The risk of MetS increased 44.6% (OR = 1.446, 95%CI: 1.414
      1.521) for males and 53.4% (OR = 1.534, 95%CI: 1.472-1.598) for females with each
      5% increase of percentage of body fat. The risk of MetS increased two-fold (OR =
      2.020, 95%CI: 1.920-2.125 for males; OR = 2.047, 95%CI: 1.954-2.144 for females
      respectively) with each 5% increase of waist-hip ratio. The risk of MetS
      increased three-fold (OR = 2.915, 95%CI: 2.742-3.099 for males; OR = 2.950,
      95%CI: 2.784-3.127 for females respectively) with each 5% increase of Waist-to
      Height Ratio (WHtR). Areas under the receiver operating curve (AUC) of most body
      composition indicators were larger than 0.70 and the sensitivities and the
      specificities of most cut-off values were larger than 0.65. AUCs of WHR and WHtR
      were the largest. The optimal cut-off values of WHtR were 0.51 for males and 0.53
      for females. CONCLUSION: MetS has become a serious public health challenge in
      China. Body composition variables were closely related to MetS and they were
      reliable indicators in the screening of the presence of MetS.

PMID- 28427376
TI  - Gender differences in walking (for leisure, transport and in total) across adult
      life: a systematic review.
AB  - BACKGROUND: The aim of this systematic review was to examine gender differences
      in walking for leisure, transport and in total in adults living in high-income
      countries, and to assess whether gender differences in walking practices change
      across the life-course. METHODS: A systematic literature search was conducted of
      publications dated 1995 to 2015. Papers providing quantitative data on
      participation in walking of both men and women aged at least 18 years in a high
      income country were screened for the quality of the data on gender differences in
      walking. Data were extracted and results were synthesised using forest plots and
      narrative summary. RESULTS: Thirty-six studies were included in the review: 18
      reported on walking for leisure, 16 on walking for transport (in total, or for
      particular purposes), and 14 on total walking. Most (33) studies provided data
      comparing the proportion of men and women who walked (at all or for a minimum
      duration) over a defined period, usually one week. There was consistent evidence
      that more women than men walk for leisure, although effect sizes were small.
      However, this effect varies by age: more younger women than younger men walk for
      leisure, but the gender difference diminishes with age and appears to reverse in
      the oldest age groups. Taking all ages together, there was no consistent gender
      difference in walking for transport or in total walking, although the small
      number of studies reporting on walking to undertake errands suggested that more
      women than men walk for this purpose. CONCLUSIONS: While there is little evidence
      that levels of total walking consistently vary by gender, our findings suggest
      that there are consistent gender differences in participation in walking for some
      purposes, including for leisure, and that there are gender differences in the
      impact of age on walking. We conclude that more research is needed to improve our
      understanding of how walking fits into the lives of women and men across the life
      course, especially in relation to gender differences in the impact of aging on
      walking. PROSPERO REGISTRATION: PROSPERO registration number: CRD42015025961 .

PMID- 28427377
TI  - A comprehensive overview of urogenital, anorectal and oropharyngeal Neisseria
      gonorrhoeae testing and diagnoses among different STI care providers: a cross
      sectional study.
AB  - BACKGROUND: Gonorrhoea, caused by Neisseria gonorrhoeae (NG), can cause
      reproductive morbidity, is increasingly becoming resistant to antibiotics and is
      frequently asymptomatic, which shows the essential role of NG test practice. In
      this study we wanted to compare NG diagnostic testing procedures between
      different STI care providers serving a defined geographic Dutch region (280,000
      inhabitants). METHODS: Data on laboratory testing and diagnosis of urogenital and
      extragenital (i.e. anorectal and oropharyngeal) NG were retrieved from general
      practitioners (GPs), an STI clinic, and gynaecologists (2006-2010). Per provider,
      we assessed their contribution regarding the total number of tests performed and
      type of populations tested, the proportion of NG positives re-tested (3-12 months
      after treatment) and test-of-cure (TOC, within 3 months post treatment). RESULTS:
      Overall, 17,702 NG tests (48.7% STI clinic, 38.2% GPs, 13.1% gynaecologists) were
      performed during 15,458 patient visits. From this total number of tests, 2257
      (12.7%) were extragenital, of which 99.4% were performed by the STI clinic. Men
      were mostly tested at the STI clinic (71%) and women by their GP (43%). NG
      positivity per visit was 1.6%; GP 1.9% (n = 111), STI clinic 1.7% (n = 131) and
      gynaecology 0.2% (n = 5). NG positivity was associated with Chlamydia trachomatis
      positivity (OR: 2.06, 95% confidence interval: 1.46-2.92). Per anatomical
      location, the proportion of NG positives re-tested were: urogenital 20.3% (n =
      36), anorectal 43.6% (n = 17) and oropharyngeal 57.1% (n = 20). NG positivity
      among re-tests was 16.9%. Proportions of NG positives with TOC by anatomical
      location were: urogenital 10.2% (n = 18), anorectal 17.9% (n = 7) and
      oropharyngeal 17.1% (n = 6). CONCLUSIONS: To achieve best practice in relation to
      NG testing, we recommend that: 1) GPs test at extragenital sites, especially men
      who have sex with men (MSM), 2) all care providers consider re-testing 3 to 12
      months after NG diagnosis and 3) TOC is performed following oropharyngeal NG
      diagnosis in settings which provide services to higher-risk men and women (such
      as STI clinics).

PMID- 28427378
TI  - Assessment of cardiac function in children with congenital adrenal hyperplasia: a
      case control study in Cameroon.
AB  - BACKGROUND: High level of androgens found in congenital adrenal hyperplasia (CAH)
      seems to have a deleterious effect on heart function. We therefore evaluate
      cardiac function of children with CAH in comparison with a healthy group.
      METHODS: We carried out a case-control study in the single endocrinology unit of
      the Mother and Child Center of Chantal Biya's Foundation. Cases were matched for
      age and genotypic sex to 2 healthy controls. We analyzed the ejection fraction
      (LVEF), fractional shortening and left ventricular mass; output and cardiac
      index; E and A waves velocities, E/A ratio and the mitral deceleration time and
      diameter of the left atrium; tricuspid annular plane systolic excursion and
      pulmonary artery systolic pressure were also measured. RESULTS: We included 19
      patients with a median age of 6.26 +/- 3.75 years and 38 controls stackable
      distribution. The left ventricular mass of cases was greater than that of
      controls. A case of reversible cardiomyopathy on hormone replacement therapy was
      found. For the cases, the average ejection fraction was 71.95 +/- 7.88%; the
      average fractional shortening was 40.67 +/- 7.02%. All these values were higher
      than those of controls, although the difference was not statistically
      significant. Diastolic left ventricular function was more impaired among the
      cases. Right ventricular function was similar in both groups. These abnormalities
      were highly correlated to the late age at diagnosis and duration of treatment.
      CONCLUSION: This study shows an altered cardiac function in CAH compared to
      healthy control and highlights importance of an early diagnosis of cases, a tight
      control of androgens levels and a regular monitoring of cardiac function.

PMID- 28427379
TI  - Novel mutation identified in severe early-onset tumor necrosis factor receptor
      associated periodic syndrome: a case report.
AB  - BACKGROUND: Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
      is the second most common heritable autoinflammatory disease, typically
      presenting in pre-school aged children with fever episodes lasting 1-3 weeks.
      Systemic symptoms can include rash, myalgia, ocular inflammation, and serositis.
      CASE PRESENTATION: Here we report an unusual presentation of TRAPS in a 7 month
      old girl who presented with only persistent fever. She was initially diagnosed
      with incomplete Kawasaki Disease and received IVIG and infliximab; however, her
      fevers quickly recurred. Subsequent testing revealed a urinary tract infection,
      but she did not improve despite appropriate therapy. As fever continued, she
      developed significant abdominal distension with imaging concerning for
      appendicitis, followed by hyperthermia and hemodynamic instability. Given her
      protracted clinical course and maternal history of a poorly defined inflammatory
      condition, an autoinflammatory disease was considered. Therapy with anakinra was
      initiated, resulting in rapid resolution of fever and normalization of
      inflammatory markers. She was found to have a previously unreported mutation,
      Thr90Pro, in the TNFRSF1A gene associated with TRAPS. This novel mutation was
      also confirmed in the patient's mother and maternal uncle. CONCLUSIONS: This
      report reviews a severe case of TRAPS in infancy associated with a novel
      mutation, Thr90Pro, in the TNFRSF1A gene, and emphasizes that autoinflammatory
      disease should be considered in the differential of infants with fever of unknown
      origin.

PMID- 28427380
TI  - The Stepping Stones and Creating Futures intervention to prevent intimate partner
      violence and HIV-risk behaviours in Durban, South Africa: study protocol for a
      cluster randomized control trial, and baseline characteristics.
AB  - BACKGROUND: Preventing intimate partner violence (IPV) remains a global public
      health challenge. Studies suggest urban informal settlements have particularly
      high levels of IPV and HIV-prevalence and these settlements are rapidly growing.
      The current evidence base of effective approaches to preventing IPV recognizes
      the potential of combining economic strengthening and gender transformative
      interventions. However, few of these interventions have been done in urban
      informal settlements, and almost none have included men as direct recipients of
      these interventions. METHODS: Stepping Stones and Creating Futures intervention
      is a participatory gender transformative and livelihoods strengthening
      intervention. It is being evaluated through a cluster randomized control trial
      amongst young women and men (18-30) living in urban informal settlements in
      eThekwini Municipality, South Africa. The evaluation includes a qualitative
      process evaluation and cost-effectiveness analysis. A comparison of baseline
      characteristics of participants is also included. DISCUSSION: This is one of the
      first large trials to prevent IPV and HIV-vulnerability amongst young women and
      men in urban informal settlements. Given the mixed methods evaluation, the
      results of this trial have the ability to develop a stronger understanding of
      what works to prevent violence against women and the processes of change in
      interventions. TRIAL REGISTRATION: NCT03022370 . Registered 13 January 2017,
      retrospectively registered.

PMID- 28427381
TI  - Penicillin treatment for patients with Community-Acquired Pneumonia in Denmark: a
      retrospective cohort study.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a severe infection, with high
      mortality. Antibiotic strategies for CAP differ across Europe. The objective of
      the study was to describe the epidemiology of CAP in Denmark and evaluate the
      prognosis of patients empirically treated with penicillin-G/V monotherapy.
      METHODS: Retrospective cohort study including hospitalized patients with x-ray
      confirmed CAP. We calculated the population-based incidence, reviewed types of
      empiric antibiotics and duration of antibiotic treatment. We evaluated the
      association between mortality and treatment with empiric penicillin-G/V using
      logistic regression analysis. RESULTS: We included 1320 patients. The incidence
      of hospitalized CAP was 3.1/1000 inhabitants. Median age was 71 years (IQR; 58
      81) and in-hospital mortality was 8%. Median duration of antibiotic treatment was
      10 days (IQR; 8-12). In total 45% were treated with penicillin-G/V as empiric
      monotherapy and they did not have a higher mortality compared to patients treated
      with broader-spectrum antibiotics (OR 0.92, CI 95% 0.55-1.53). CONCLUSION: The
      duration of treatment exceeded recommendations in European guidelines. Empiric
      monotherapy with penicillin-G/V was commonly used and not associated with
      increased mortality in patients with mild to moderate pneumonia. Our results are
      in agreement with current conservative antibiotic strategy as outlined in the
      Danish guidelines.

PMID- 28427382
TI  - Splenectomy before adult liver transplantation: a retrospective study.
AB  - BACKGROUND: A considerable number of patients with portal hypertension (PHT) have
      to undergo splenectomy because they do not meet the requirements for liver
      transplantation (LT) or cannot find a suitable liver donor. However, it is not
      known whether pre-transplantation splenectomy may create occult difficulties for
      patients who require LT in future. METHODS: We analyzed 1059 consecutive patients
      who underwent adult liver transplantation (ADLT). Patients with pre
      transplantation splenectomy Sp(+) and without splenectomy Sp(-) were compared
      using a propensity score analysis to create the best match between groups.
      RESULTS: There were no differences between patients in group Sp(+) and group Sp(
      ) with respect to the main post-operative infections (12.20% vs. 15.85%, P =
      0.455), and the incidence of major complications (6.10% vs. 10.98%, P = 0.264).
      The post-operative platelet count was significantly higher in group Sp(+) (P =
      0.041), while group Sp(-) had a higher rate of post-operative thrombocytopenia
      (91.46% vs. 74.39%, P = 0.006) and early allograft dysfunction (EAD) (23.20% vs.
      10.98%, P = 0.038). The 5-year overall survival rates were similar in groups Sp(
      ) and Sp(+) (69.7% vs. 67.6%, P = 0.701). CONCLUSIONS: Compared with Sp(-), the
      risk of infection and post-operative complications in group Sp(+) was not
      increased, while group Sp(-) had a higher rate of post-operative EAD. Moreover,
      pre-transplantation splenectomy is very effective for the prevention of
      thrombocytopenia after LT. Pre-transplantation splenectomy is recommended in
      cases with risky PHT patients without appropriate source of liver for LT.

PMID- 28427384
TI  - Imbalanced target prediction with pattern discovery on clinical data
      repositories.
AB  - BACKGROUND: Clinical data repositories (CDR) have great potential to improve
      outcome prediction and risk modeling. However, most clinical studies require
      careful study design, dedicated data collection efforts, and sophisticated
      modeling techniques before a hypothesis can be tested. We aim to bridge this gap,
      so that clinical domain users can perform first-hand prediction on existing
      repository data without complicated handling, and obtain insightful patterns of
      imbalanced targets for a formal study before it is conducted. We specifically
      target for interpretability for domain users where the model can be conveniently
      explained and applied in clinical practice. METHODS: We propose an interpretable
      pattern model which is noise (missing) tolerant for practice data. To address the
      challenge of imbalanced targets of interest in clinical research, e.g., deaths
      less than a few percent, the geometric mean of sensitivity and specificity (G
      mean) optimization criterion is employed, with which a simple but effective
      heuristic algorithm is developed. RESULTS: We compared pattern discovery to
      clinically interpretable methods on two retrospective clinical datasets. They
      contain 14.9% deaths in 1 year in the thoracic dataset and 9.1% deaths in the
      cardiac dataset, respectively. In spite of the imbalance challenge shown on other
      methods, pattern discovery consistently shows competitive cross-validated
      prediction performance. Compared to logistic regression, Naive Bayes, and
      decision tree, pattern discovery achieves statistically significant (p-values <
      0.01, Wilcoxon signed rank test) favorable averaged testing G-means and F1-scores
      (harmonic mean of precision and sensitivity). Without requiring sophisticated
      technical processing of data and tweaking, the prediction performance of pattern
      discovery is consistently comparable to the best achievable performance.
      CONCLUSIONS: Pattern discovery has demonstrated to be robust and valuable for
      target prediction on existing clinical data repositories with imbalance and
      noise. The prediction results and interpretable patterns can provide insights in
      an agile and inexpensive way for the potential formal studies.

PMID- 28427383
TI  - Is ischemia the only factor predicting cardiovascular outcomes in all diabetes
      mellitus patients?
AB  - Diabetes mellitus (DM) is associated with an excess in cardiovascular morbidity
      and mortality, and is characterized by increased rates of coronary artery
      disease. Furthermore, once atherosclerosis is established, this is associated
      with an increased extent, complexity and a more rapid progression than seen in
      non-DM patients. Ischemia is the single most important predictor of future hard
      cardiac events and ischemia correction remains the cornerstone of current
      revascularization strategies. However recent data suggests that, in DM patients,
      coronary atherosclerosis despite the absence of ischemia, detected by either
      invasive or non-invasive methods, may not be associated with the same low risk of
      future cardiac events as seen in non-DM patients. This review seeks to examine
      the current evidence supporting an ischemia driven revascularization strategy,
      and to challenge the notion that ischemia is the only clinically relevant factor
      in the prediction of cardiovascular outcomes in all-comer DM patients.
      Specifically, we examine whether in DM patients certain characteristics beyond
      ischemia, such as microvascular disease, coronary atherosclerosis burden,
      progression and plaque composition, may need to be considered for a more refined
      risk stratification in these high-risk patients.

PMID- 28427385
TI  - Differences between native and prosthetic knees in terms of cross-sectional
      morphology of the femoral trochlea: a study based on three-dimensional models and
      virtual total knee arthroplasty.
AB  - BACKGROUND: The cross-sectional morphology of the prosthetic knee is crucial to
      understanding patellar motion and quadriceps strength after total knee
      arthroplasty. However, few comparative evaluations of the cross-sectional
      morphology of the femoral trochlea have been performed in the native knee and
      currently available femoral implants, and the relationship between the trochlear
      anatomy of prosthetic components and post-operative patellofemoral complications
      remains unclear. We aimed to investigate the differences in cross-sectional
      morphology of the femoral trochlea between native knees and prosthetic femoral
      components. METHODS: Virtual total knee arthroplasty was performed, whereby four
      different femoral components (medial-pivot, Triathlon, NRG and NexGen) were
      virtually superimposed onto three-dimensional models of 42 healthy femurs. The
      following morphological parameters were measured in three cross-sections (0, 45
      and 90 degrees ) of the femoral trochlea: sulcus height, lateral tilt angle,
      medial tilt angle and sulcus angle. Only statistically significant differences
      are described further (p < 0.05). RESULTS: In the 0 degrees  cross-section,
      sulcus height was smaller in the native knee than in the Triathlon, NRG and
      NexGen components; all prosthetic components had smaller lateral tilt angles and
      larger medial tilt angles. In the 45 degrees  cross-section, sulcus height was
      larger in the native knee than in the medial-pivot, Triathlon and NexGen
      components; both lateral and medial tilt angles were smaller in the prosthetic
      components. In the 90 degrees  cross-section, sulcus height was smaller in the
      native knee than in the medial-pivot component; all prosthetic components had a
      larger lateral tilt angle and smaller medial tilt angle. In all cross-sections,
      the sulcus angle was smaller in the native knee. CONCLUSIONS: The discrepancy
      between native and prosthetic trochlear geometries suggests altered knee
      mechanics after total knee arthroplasty, but further cadaveric, computational or
      fluoroscopic investigations are necessary to clarify the implications of this
      observation. Our findings can be used to optimize biomechanical guidelines for
      total knee arthroplasty (patellar resurfacing or non-resurfacing) in Chinese
      individuals so as to decrease the risk of patellar lateral dislocation, to
      maintain stability and to optimize extensor kinematics.

PMID- 28427386
TI  - Heterogeneous distributional responses to climate warming: evidence from rodents
      along a subtropical elevational gradient.
AB  - BACKGROUND: Understanding whether species' elevational range is shifting in
      response to directional changes in climate and whether there is a predictable
      pattern in that response is one of the major challenges in ecology. However, so
      far very little is known about the distributional responses of subtropical
      species to climate change, especially for small mammals. In this study, we
      examined the elevational range shifts at three range points (upper and lower
      range limits and abundance-weighted range centre) of rodents over a 30-year
      period (1986 to 2014-2015), in a subtropical forest of Southwest China. We also
      examined the influences of four ecological traits (body mass, habitat breadth,
      diet and daily activity pattern) on the upslope shifts in species' abundance
      weighted range centres. RESULTS: Despite the warming trend between 1986 and 2015,
      the 11 rodent species in analysis displayed heterogeneous dynamics at each of the
      three range points. Species which have larger body sizes and narrower habitat
      breadths, show both diurnal and nocturnal activities and more specialized dietary
      requirements, are more likely to exhibit upslope shifts in abundance-weighted
      range centres. CONCLUSIONS: Species' distributional responses can be
      heterogeneous even though there are directional changes in climate. Our study
      indicates that climate-induced alleviation of competition and lag in response may
      potentially drive species' range shift, which may not conform to the expectation
      from climate change. Difference in traits can lead to different range dynamics.
      Our study also illustrates the merit of multi-faceted assessment in studying
      elevational range shifts.

PMID- 28427387
TI  - Serum MicroRNA profile in patients with colon adenomas or cancer.
AB  - BACKGROUND: Colon cancer, one of the most common causes of cancer-related deaths,
      arises from adenomatous polyps. In these years, circulating microRNAs (miRNAs)
      have attracted increasing attention as novel biomarkers for colon cancers. The
      dysregulated circulating miRNAs in patients with colon adenomas has not been well
      understood. METHODS: Here, we aimed to identify miRNA profile in the serum of
      patients with colon adenomas or colon cancer by using microarray. Then we
      validated eight differentially expressed miRNAs (DEMs) by qRT-PCR and predicted
      their targets. RESULTS: We identified 26 DEMs from Adenomas versus Normal
      comparison (11 up-regulations and 15 down-regulations), 72 DEMs from Cancer
      versus Normal comparison (19 up-regulations and 53 down-regulations) and 17 DEMs
      from Cancer versus Adenomas comparison (4 up-regulations and 13 down
      regulations). Moreover, three DEMs identified from Cancer versus Normal
      comparison were included in the list of DEMs identified from Cancer versus
      Adenomas comparison, and may be specific diagnostic biomarkers for colon cancer.
      Five down-regulated miRNAs identified from Cancer versus Normal comparison were
      included in the list of DEMs identified from Adenomas versus Normal comparison,
      and may be important for the development of colon polyps and cancer. CONCLUSIONS:
      We discovered 8 circulating miRNAs associated with colon adenomas and colon
      cancer, and these miRNAs may potentially serve as noninvasive screening
      biomarkers for colon cancer. Our study is useful for expanding our understanding
      in the development of colon adenomas and colon cancer, and thus provide novel
      insights into colon cancer pathogenesis and prevention.

PMID- 28427388
TI  - Movement cognition and narration of the emotions treatment versus standard speech
      therapy in the treatment of children with borderline intellectual functioning: a
      randomized controlled trial.
AB  - BACKGROUND: Borderline intellectual functioning (BIF) is defined as a "health
      meta-condition... characterized by various cognitive dysfunctions associated with
      an intellectual quotient (IQ) between 71 and 85 which determines a deficit in the
      individual's functioning both in the restriction of activities and in the
      limitation of social participation". It can be caused by many factors, including
      a disadvantaged background and prematurity. BIF affects 7-12% of primary school
      children that show academic difficulties due to poor executive functioning. In
      many children with BIF, language, movement and social abilities are also
      affected, making it difficult to take part in daily activities. Dropping out of
      school and psychological afflictions such as anxiety and depression are common in
      children with BIF. This study investigates whether an intensive rehabilitation
      program that involves all of the areas affected in children with BIF (Movement,
      Cognition and Narration of emotions, MCNT) is more effective than Standard Speech
      Therapy (SST). METHODS: This is a multicenter interventional single blind
      randomized controlled study. Children aged between 6 to 11 years who attend a
      mainstream primary school and have multiple learning difficulties, behavioral
      problems and an IQ ranging between 85 to 70 have been enrolled. Participants are
      randomly allocated to one of three groups. The first group receives individual
      treatment with SST for 45 min, twice a week for 9 months. The second group
      receives the experimental treatment MCNT for 3 h per day, 5 days/ week for 9
      months and children work in small groups. The third group consists of children on
      a waiting list for the SST for nine months. DISCUSSION: BIF is a very frequent
      condition with no ad hoc treatment. Over the long term, there is a high risk to
      develop psychiatric disorders in adulthood. Due to its high social impact, we
      consider it very important to intervene during childhood so as to intercept the
      remarkable plasticity of the developing brain. TRIAL REGISTRATION: "Study Let
      them grow: A new intensive and multimodal Treatment for children with borderline
      intellectual functioning based on Movement, Cognition and Narration of emotions",
      retrospectively registered in ISRCTN Register with ISRCTN81710297 at 2017-01-09.

PMID- 28427389
TI  - Defining micro-epidemiology for malaria elimination: systematic review and meta
      analysis.
AB  - BACKGROUND: Malaria risk can vary markedly between households in the same
      village, or between villages, but the determinants of this "micro
      epidemiological" variation in malaria risk remain poorly understood. This study
      aimed to identify factors that explain fine-scale variation in malaria risk
      across settings and improve definitions and methods for malaria micro
      epidemiology. METHODS: A systematic review of studies that examined risk factors
      for variation in malaria infection between individuals, households, clusters,
      hotspots, or villages in any malaria-endemic setting was conducted. Four
      databases were searched for studies published up until 6th October 2015. Crude
      and adjusted effect estimates for risk factors for malaria infection were
      combined in random effects meta-analyses. Bias was assessed using the Newcastle
      Ottawa Quality Assessment Scale. RESULTS: From 743 retrieved records, 51 studies
      were selected, representing populations comprising over 160,000 individuals in 21
      countries, in high- and low-endemicity settings. Sixty-five risk factors were
      identified and meta-analyses were conducted for 11 risk factors. Most studies
      focused on environmental factors, especially increasing distance from a breeding
      site (OR 0.89, 95% CI 0.86-0.92, 10 studies). Individual bed net use was
      protective (OR 0.63, 95% CI 0.52-0.77, 12 studies), but not household bed net
      ownership. Increasing household size (OR 1.08, 95% CI 1.01-1.15, 4 studies) and
      household crowding (OR 1.79, 95% CI 1.48-2.16, 4 studies) were associated with
      malaria infection. Health seeking behaviour, medical history and genetic traits
      were less frequently studied. Only six studies examined whether individual-level
      risk factors explained differences in malaria risk at village or hotspot level,
      and five studies reported different risk factors at different levels of analysis.
      The risk of bias varied from low to high in individual studies. Insufficient
      reporting and comparability of measurements limited the number of meta-analyses
      conducted. CONCLUSIONS: Several variables associated with individual-level
      malaria infection were identified, but there was limited evidence that these
      factors explain variation in malaria risk at village or hotspot level. Social,
      population and other factors may confound estimates of environmental risk
      factors, yet these variables are not included in many studies. A structured
      framework of malaria risk factors is proposed to improve study design and quality
      of evidence in future micro-epidemiological studies.

PMID- 28427391
TI  - Fish with red fluorescent eyes forage more efficiently under dim, blue-green
      light conditions.
AB  - BACKGROUND: Natural red fluorescence is particularly conspicuous in the eyes of
      some small, benthic, predatory fishes. Fluorescence also increases in relative
      efficiency with increasing depth, which has generated speculation about its
      possible function as a "light organ" to detect cryptic organisms under bluish
      light. Here we investigate whether foraging success is improved under ambient
      conditions that make red fluorescence stand out more, using the triplefin
      Tripterygion delaisi as a model system. We repeatedly presented 10 copepods to
      individual fish (n = 40) kept under a narrow blue-green spectrum and compared
      their performance with that under a broad spectrum with the same overall
      brightness. The experiment was repeated for two levels of brightness, a shaded
      one representing 0.4% of the light present at the surface and a heavily shaded
      one with about 0.01% of the surface brightness. RESULTS: Fish were 7% more
      successful at catching copepods under the narrow, fluorescence-friendly spectrum
      than under the broad spectrum. However, this effect was significant under the
      heavily shaded light treatment only. CONCLUSIONS: This outcome corroborates
      previous predictions that fluorescence may be an adaptation to blue-green,
      heavily shaded environments, which coincides with the opportunistic biology of
      this species that lives in the transition zone between exposed and heavily shaded
      microhabitats.

PMID- 28427390
TI  - Advanced glycation end-products decreases expression of endothelial nitric oxide
      synthase through oxidative stress in human coronary artery endothelial cells.
AB  - BACKGROUND: Advanced glycation end-products (AGEs) are elevated under diabetic
      conditions and associated with insulin resistance, endothelial dysfunction and
      vascular inflammation in humans. It has been demonstrated that AGEs evoke
      oxidative and inflammatory reactions in endothelial cells through the interaction
      with a receptor for AGEs (RAGE). Here, we aimed to identify the cellular
      mechanisms by which AGEs exacerbate the endothelial dysfunction in human coronary
      artery endothelial cells (HCAECs). METHODS: 30 type 2 diabetic patients with or
      without coronary artery atherosclerosis were recruited for this study. Plasma
      levels of AGE peptides (AGE-p) were analyzed using flow injection assay.
      Endothelial function was tested by brachial artery flow-mediated vasodilatation
      (FMD). Further investigations were performed to determine the effects and
      mechanisms of AGEs on endothelial dysfunction in HCAECs. RESULTS: AGE-p was
      inversely associated with FMD in diabetic patients with coronary artery
      atherosclerosis in our study. After treated with AGEs, HCAECs showed significant
      reductions of eNOS mRNA and protein levels including eNOS and phospho-eNOS
      Ser1177, eNOS mRNA stability, eNOS enzyme activity, and cellular nitric oxide
      (NO) levels, whereas superoxide anion production was significantly increased. In
      addition, AGEs significantly decreased mitochondrial membrane potential, ATP
      content and catalase and superoxyde dismutase (SOD) activities, whereas it
      increased NADPH oxidase activity. Treatment of the cells with antioxidants SeMet,
      SOD mimetic MnTBAP and mitochondrial inhibitor thenoyltrifluoroacetone (TTFA)
      effectively blocked these effects induced by AGEs. AGEs also increased
      phosphorylation of the mitogen-activated protein kinases p38 and ERK1/2, whereas
      the specific inhibitors of p38, ERK1/2, and TTFA effectively blocked AGEs-induced
      reactive oxygen species production and eNOS downregulation. CONCLUSIONS: AGEs
      cause endothelial dysfunction by a mechanism associated with decreased eNOS
      expression and increased oxidative stress in HCAECs through activation of p38 and
      ERK1/2.

PMID- 28427392
TI  - Percutaneous intervention versus coronary artery bypass graft surgery in left
      main coronary artery stenosis: a systematic review and meta-analysis.
AB  - BACKGROUND: The optimal revascularization technique in patients with left main
      coronary artery disease (CAD) remains controversial. We aimed to compare the long
      term performance of percutaneous coronary intervention (PCI) versus coronary
      artery bypass graft (CABG) surgery in treatment of left main CAD. METHODS:
      PubMed, EMBASE, and the Cochrane Library were searched until November 16, 2016.
      RESULTS: Six randomized controlled trials and 22 matched observational studies
      including 22,487 patients and 90,167 patient-years of follow-up were included.
      PCI was associated with an overall higher risk for the major adverse cardiac and
      cerebrovascular events (hazard ratio (HR), 1.42; 95% confidence interval (CI),
      1.14-1.77), mainly driven by higher rates of myocardial infarction (HR, 1.69; 95%
      CI, 1.22-2.34) and revascularization (HR, 2.80; 95% CI, 1.86-4.22). The overall
      risks for all-cause death (HR, 1.05; 95% CI, 0.93-1.20), cardiac death (HR, 1.05;
      95% CI, 0.69-1.59), stroke (HR, 0.64; 95% CI, 0.33-1.24), and the composite
      safety endpoint of death, myocardial infarction, or stroke (HR, 1.06; 95% CI,
      0.97-1.16) were similar between PCI and CABG. Stratified analysis based on stent
      types showed that the increased risk for myocardial infarction associated with
      PCI was only evident in patients with bare-metal stents or early-generation drug
      eluting stents (DES), but not newer-generation DES. Stratified analyses based on
      study designs showed largely similar findings with the overall analyses, except
      for a significantly higher incidence of myocardial infarction in adjusted studies
      (HR, 2.01; 95% CI, 1.64-2.45) but a trend toward higher incidence in randomized
      trials (HR, 1.39; 95% CI, 0.85-2.27) associated with PCI. CONCLUSIONS: Compared
      with CABG, PCI with newer-generation DES might be a safe alternative
      revascularization strategy for treatment of left main CAD, but is associated with
      more repeat revascularization.

PMID- 28427393
TI  - Correlation between intervertebral disc degeneration, paraspinal muscle atrophy,
      and lumbar facet joints degeneration in patients with lumbar disc herniation.
AB  - BACKGROUND: To assess the correlation between lumbar disc degeneration (LDD),
      multifidus muscle atrophy (LMA), and facet joints degeneration in patients with
      L4-L5 lumbar disc herniation (LDH). METHODS: Sixty patients with L4-L5 LDH
      diagnosed by a 1.5 T MRI scanner were enrolled in the study group and another 60
      patients with non-specific back pain were enrolled in the control group. LDD,
      LMA, and facet joints degeneration were examined and analyzed independently by
      two independent orthopedic surgeons using T2-weighted images. Wilcoxon test was
      used for analyzing the difference of LDD and facet joints degeneration between L3
      L4 and L5-S1 and difference of LMA between the herniated and control groups.
      Correlation analysis of the three degeneration grades at the same level was
      determined by Spearman rank correlation test. RESULTS: In the herniated group,
      most LMA at L3-L4 level was grade 1 (42, 70.0%); grade 2 (33, 55.0%) at L4-L5
      level; and grade 3 (27, 45.0%) at L5-S1 level. LMA and LDD grading were
      significantly different between L3-L4 and L5-S1 levels (P < 0.05). In the
      herniation group, the Spearman value for LDD and LMA grading were 0.352 (P <
      0.01) at L3-L4 and 0.036 (P > 0.05) at the L5-S1 level. The differences in LMA
      between the herniated and control groups at the three levels were significant (P
      < 0.05). CONCLUSIONS: Disc degeneration and multifidus muscles atrophy were
      positively correlated at the L3-L4 disc level. A lumbar extension muscle
      strengthening program could be helpful in preventing muscle atrophy and lumbar
      spinal degeneration.

PMID- 28427394
TI  - Erratum to: Obesity and type 2 diabetes have additive effects on left ventricular
      remodelling in normotensive patients-a cross sectional study.

PMID- 28427395
TI  - Protein antigen of bird-related hypersensitivity pneumonitis in pigeon serum and
      dropping.
AB  - BACKGROUND: Avian antigen is a common cause of hypersensitivity pneumonitis (HP).
      Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits
      a hypersensitivity reaction in patients with bird-related hypersensitivity
      pneumonitis (BRHP), but the antigenic components in these materials have yet to
      be fully elucidated. METHOD: Pigeon serum, pigeon intestine homogenates, and PDE
      were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with
      summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers. Among
      the protein spots found in both pigeon serum and PDE, those that reacted with
      sera from BRHP patients were identified by mass spectrometry. Immunoassays using
      recombinant protein were performed to confirm the antigenicity of the identified
      protein. Cytokine production by peripheral blood mononuclear cells (PBMCs)
      stimulated with recombinant protein was also assessed. RESULTS: Immunoglobulin
      lambda-like polypeptide-1 (IGLL-1) was identified from all spots on 2-DE
      immunoblots of both pigeon serum and PDE. The BRHP patients exhibited higher
      levels of serum IgG antibody against the recombinant IGLL-1 (rIGLL-1) compared to
      the control subjects, as well as a stronger PBMCs proliferative response to rIGLL
      1. Cytokine production by PBMCs from BRHP patients after rIGLL-1 exposure
      indicated that the protein could induce Th1 prone immune responses: an increase
      in TNF-alpha and an absence of elevated IL-10 production. CONCLUSIONS: Pigeon
      IGLL-1 was identified as the BRHP antigen present in both pigeon serum and PDE.

PMID- 28427396
TI  - DEMDATA: The Austrian-Czech institutional long term care project - design and
      protocol of a two-centre cross sectional study.
AB  - BACKGROUND: The organization of long-term care is one of the main challenges of
      public health and health policies in Europe and worldwide, especially in terms of
      care concepts for people with dementia. In Austria and the Czech Republic the
      majority of elderly institutionalized persons with dementia are cared for in
      nursing homes. It is however unclear, how many persons living in nursing homes in
      Austria and in the Czech Republic are suffering from cognitive impairment and
      dementia. In addition, basic information on the nutritional status, the status of
      mobility and the medication prescription patterns are often missing. To
      facilitate new effective and evidenced based care concepts, basic epidemiological
      data are in urgent need. Thus, DEMDATA was initiated to provide important basic
      data on persons living in nursing homes in Austria and the Czech Republic for
      future care planning. METHODS: DEMDATA is a multicentre mixed methods cross
      sectional study. Stratified and randomly drawn nursing homes in Austria and the
      Czech Republic are surveyed. The study protocol used in both study centres
      assesses four different domains: a) Resident, b) Care team, c) Relative and d)
      Environmental Factors. Resident's data include among others health status,
      cognition, dementia, mobility, nutrition, behavioural symptoms, pain intensity
      and quality of life. A minimum of 500 residents per country are included into the
      study (N = 1000 residents). The care team is asked about the use of the person
      centred care and their burden. The relatives are asked about the number of visits
      and proxy-rate the quality of life of their family member. All staff employed in
      the nursing homes, all residents and relatives can voluntary take part in the
      study. The environmental factors include among others the organisational category
      of the nursing home, number of residents, number of rooms, social activities and
      the care concept. The project started in March 2016 and will be concluded in
      February 2018. DISCUSSION: DEMDATA will provide important epidemiological data on
      four different nursing home domains in Austria and the Czech Republic, with a
      focus on the prevalence of dementia in this population. Thereby supplying
      decision and policy makers with important foundation for future care planning.

PMID- 28427397
TI  - HVC1 ameliorates hyperlipidemia and inflammation in LDLR-/- mice.
AB  - BACKGROUND: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis),
      Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of
      Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although
      the components are known to be effective in various conditions such as
      inflammation, hypertension, and hypercholesterolemia, there are no reports of the
      molecular mechanism of its hypolipidemic effects. METHODS: We investigated the
      hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR
      /-) mice fed a high-cholesterol diet for 13 weeks. Mice were randomized in to 6
      groups: ND (normal diet) group, HCD (high-cholesterol diet) group, and treatment
      groups fed HCD and treated with simvastatin (10 mg/kg, p.o.) or HVC1 (10, 50, or
      250 mg/kg, p.o.). RESULTS: HVC1 regulated the levels of total cholesterol,
      triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density
      lipoprotein (HDL) cholesterol in mouse serum. In addition, it regulated the
      transcription level of the peroxisome proliferator-activated receptors (PPARs),
      sterol regulatory element-binding proteins (SREBP)-2, 3-hydroxy-3-methylglutaryl
      (HMG)-CoA reductase, lipoprotein lipase (LPL), apolipoprotein B (apo B), liver X
      receptor (LXR), and inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha).
      Furthermore, HVC1 activated 5' adenosine monophosphate-activated protein kinase
      (AMPK). CONCLUSION: Our results suggest that HVC1 might be effective in
      preventing high-cholesterol diet-induced hyperlipidemia by regulating the genes
      involved in cholesterol and lipid metabolism, and inflammatory responses.

PMID- 28427398
TI  - Euphorbia dracunculoides L. abrogates carbon tetrachloride induced liver and DNA
      damage in rats.
AB  - BACKGROUND: Evaluation of Euphorbia dracunculoides of family Euphorbiaceae during
      previous studies had established the in vitro antioxidant and in vivo anti
      inflammatory activities. The plant is used by the local communities of Pakistan
      for various disorders including rheumatism and edema. In this investigation we
      have evaluated the hepatoprotective effects against CCl4 induced toxicity in rat.
      METHODS: Dry powder of the aerial parts of E. dracunculoides was extracted with
      95% methanol to get the extract (EDME). To investigate the hepatoprotective
      effects of EDME the Sprague-Dawley male rats were divided in to 8 groups with 6
      rats in each. Group I and II were the normal and vehicle treated while the Groups
      III-VI were injected intraperitoneally with 1 ml of CCl4 (30% in olive oil). Rats
      of Group IV were orally administered with silymarin (50 mg/kg) while the Group V
      and VI with 200 mg/kg and 400 mg/kg of EDME, respectively. Animals of Group VII
      (200 mg/kg) and VIII (400 mg/kg) were treated with EDME alone. The treatments
      were given thrice a week for 4 weeks. Effects of EDME were evaluated for the
      protective effects against oxidative stress and genotoxicity induced with CCl4 in
      liver of rat. RESULTS: Analysis of serum indicated significant (p < 0.05) rise in
      the level of aspartate transaminase (AST), alanine transaminase (ALT), alkaline
      phosphatase (ALP) and globulin whereas decrease was recorded for the total
      protein and albumin in CCl4 treated rats. In liver tissues the activity level of
      catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S
      transferase (GST), glutathione (GSH) was decreased while the level of lipid
      peroxides; thiobarbituric acid reactant substances (TBARS), nitrite and hydrogen
      peroxide increased in CCl4 treated rats as compared to the control group.
      Histopathological injuries and DNA damages were recorded in liver of rat with
      CCl4 treatment. However, co-administration of EDME, dose dependently, ameliorated
      the CCl4-induced hepatic toxicity in these parameters. CONCLUSIONS: These results
      suggested that the phyto-constituents of EDME were able to ameliorate the
      oxidative stress induced with CCl4 and can be a useful therapeutic agent for
      oxidative stress related disorders.

PMID- 28427399
TI  - Erratum to: Successes and failures: what did we learn from recent first-line
      treatment immunotherapy trials in non-small cell lung cancer?

PMID- 28427400
TI  - Monitoring mandibular movements to detect Cheyne-Stokes Breathing.
AB  - BACKGROUND: The patterns of mandibular movements (MM) during sleep can be used to
      identify increased respiratory effort periodic large-amplitude MM (LPM), and
      cortical arousals associated with "sharp" large-amplitude MM (SPM). We
      hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic
      abnormal MM patterns. The present study aims to evaluate prospectively the
      concordance between CSB detected by periodic MM and polysomnography (PSG) as gold
      standard. The present study aims to evaluate prospectively the concordance
      between CSB detected by periodic MM and polysomnography (PSG) as gold-standard.
      METHODS: In 573 consecutive patients attending an in-laboratory PSG for suspected
      sleep disordered breathing (SDB), MM signals were acquired using magnetometry and
      scored manually while blinded from the PSG signal. Data analysis aimed to verify
      the concordance between the CSB identified by PSG and the presence of LPM or SPM.
      The data were randomly divided into training and validation sets (985 5-min
      segments/set) and concordance was evaluated using 2 classification models.
      RESULTS: In PSG, 22 patients (mean age +/- SD: 65.9 +/- 15.0 with a sex ratio M/F
      of 17/5) had CSB (mean central apnea hourly indice +/- SD: 17.5 +/- 6.2) from a
      total of 573 patients with suspected SDB. When tested on independent subset, the
      classification of CSB based on LPM and SPM is highly accurate (Balanced-accuracy
      = 0.922, sensitivity = 0.922, specificity = 0.921 and error-rate = 0.078).
      Logistic models based odds-ratios for CSB in presence of SPM or LPM were 172.43
      (95% CI: 88.23-365.04; p < 0.001) and 186.79 (95% CI: 100.48-379.93; p < 0.001),
      respectively. CONCLUSION: CSB in patients with sleep disordered breathing could
      be accurately identified by a simple magnetometer device recording mandibular
      movements.

PMID- 28427401
TI  - Ki-67 protein expression and tumor associated inflammatory cells (macrophages and
      mast cells) in canine colorectal carcinoma.
AB  - BACKGROUND: Ki67 index, tumor associated macrophages (TAMs) and mast cells (MCs)
      are associated with malignancies in animal and human neoplasms including
      colorectal carcinomas (CRC). This has not been assessed in canine CRC. Given
      similar genetic abnormalities between human and canine CRC, we assessed Ki-67 and
      mitotic indices, TAMs and MC count (MCC) in canine CRC (n = 17). TAMs and MCC
      were compared with those in adenomas (n = 13) and control (n = 9). RESULTS: Ki-67
      index in CRC (17.13 +/- 11.50) was strongly correlated (r = 0.98, p < 0.05) with
      mitotic index (3.52 +/- 1.80). MCC was higher (p < 0.05) in CRC (6.30 +/- 3.98)
      than in adenomas (0.78 +/- 0.77) and control (0.35 +/- 0.33). The results suggest
      that Ki-67 index and MCC are associated with malignancy in canine CRC. Higher
      average TAMs were counted in adenomas (21.30 +/- 20.70) and in CRC (11.00 +/-
      9.82) than in the control (7.69 +/- 7.26), although the differences were not
      significant (p > 0.05). CONCLUSION: Ki-67 index, TAMs and MCC in canine CRC were
      recorded for the first time in this study. Ki-67 index and MCC are associated
      with malignancy in canine CRC. Quantitative assessment of MCs and Ki-67 coupled
      with mitotic index and other clinical parameters may help in evaluating
      malignancy in canine CRC. TAMs likely play a role in the development of canine
      colorectal tumors. Further studies to determine the clinical significance of
      these parameters for prognostic, chemo-preventive and chemotherapeutic purposes
      in canine colorectal tumors are recommended.

PMID- 28427402
TI  - Fluorescence cholangiography during laparoscopic cholecystectomy in a patient
      with situs inversus totalis: a case report and literature review.
AB  - BACKGROUND: Situs inversus totalis is a rare autosomal disorder in which the
      patient's affected visceral organs are a perfect mirror image of their normal
      positions. Surgery in these patients is technically challenging. Minimally
      invasive surgery such as laparoscopic cholecystectomy is the standard treatment
      for symptomatic cholelithiasis, but it can be difficult to perform. Laparoscopic
      cholecystectomy in patients with situs inversus totalis may be even more
      technically challenging. Fluorescence cholangiography is a new innovation in the
      field of navigation surgery. This procedure is safe and easy to perform, its
      findings are easy to interpret, and it does not require a learning curve or
      radiographs. It can be used in real time during surgery to identify extrahepatic
      biliary structures. CASE PRESENTATION: We herein report a case of situs inversus
      totalis in a Thai patient with a history of biliary pancreatitis. He underwent
      laparoscopic cholecystectomy with intraoperative fluorescence cholangiography.
      The operation was successfully completed without complications. To the best of
      our knowledge, this is the first case report of the use of fluorescence
      cholangiography during laparoscopic cholecystectomy in a patient with situs
      inversus. CONCLUSION: Fluorescence cholangiographyis a new navigational surgical
      technique with which to identify extrahepatic biliary structures. It can be used
      as an adjunct technique during laparoscopic cholecystectomy to avoid biliary
      tract injury in difficult cases.

PMID- 28427403
TI  - Preoperative carbohydrate load and intraoperatively infused omega-3
      polyunsaturated fatty acids positively impact nosocomial morbidity after coronary
      artery bypass grafting: a double-blind controlled randomized trial.
AB  - BACKGROUND: A strategy of limited preoperative fasting, with carbohydrate (CHO)
      loading and intraoperative infusion of omega-3 polyunsaturated fatty acids (omega
      3 PUFA), has seldom been tried in cardiovascular surgery. Brief fasting, followed
      by CHO intake 2 h before anesthesia, may improve recovery from CABG procedures
      and lower perioperative vasoactive drug requirements. Infusion of omega-3 PUFA
      may reduce occurrences of postoperative atrial fibrillation (POAF) and shorten
      hospital stays. The aim of this study was to assess morbidity (especially POAF)
      in ICU patients after coronary artery bypass grafting (CABG)/cardiopulmonary
      bypass (CPB) in combination, if preoperative fasts are curtailed in favor of CHO
      loading, and omega-3 PUFA are infused intraoperatively. METHODS: Fifty-seven
      patients undergoing CABG were randomly assigned to receive 12.5% maltodextrin
      (200 ml, 2 h before anesthesia), without infusing omega-3 PUFA (CHO, n = 14);
      water (200 ml, 2 h before anesthesia), without infusing omega-3 PUFA (controls, n
      = 14); 12.5% maltodextrin (200 ml, 2 h before anesthesia) plus intraoperative
      omega-3 PUFA (0.2 mcg/kg) (CHO + W3, n = 15); or water (200 ml, 2 h before
      anesthesia) plus intraoperative omega-3 PUFA (0.2 mcg/kg) (W3, n = 14).
      Perioperative clinical variables and mortality were analyzed, examining the
      incidence of POAF, as well as the need for inotropic vasoactive drugs during
      surgery and in ICU. RESULTS: Two deaths occurred (3.5%), but there were no
      instances of bronchoaspiration and mediastinitis. Neither ICU stays nor total
      postoperative stays differed by group (P > 0.05). Patients given preoperative CHO
      loads (CHO and CHO + W3 groups) experienced fewer instances of hospital infection
      (RR = 0.29, 95%CI 0.09-0.94; P = 0.023) and were less reliant on vasoactive
      amines during surgery (RR = 0.60, 95% CI 0.38-0.94; P = 0.020). Similarly, the
      number of patients requiring vasoactive drugs while recovering in ICU differed
      significantly by group (P = 0.008), showing benefits in patients given CHO loads.
      The overall incidence of POAF was 29.8% (17/57), differing significantly by group
      (P = 0.009). Groups given omega-3 PUFA (W3 and CHO + W3 groups) experienced
      significantly fewer instances of POAF (RR = 4.83, 95% CI 1.56-15.02; P = 0.001).
      CONCLUSION: Preoperative curtailment of fasting was safe in this cohort. When
      implemented in conjunction with CHO loading and infusion of omega-3 PUFA during
      surgery, expedited recovery from CABG with CPB was observed. TRIAL REGISTRATION:
      NCT: 03017001.

PMID- 28427404
TI  - Retraction Note: Evaluation of low-cost custom made VAC therapy compared with
      conventional wound dressings in the treatment of non-healing lower limb ulcers in
      lower socio-economic group patients of Kashmir valley.

PMID- 28427405
TI  - Ceiling effect in EMR system assimilation: a multiple case study in primary care
      family practices.
AB  - BACKGROUND: There has been indisputable growth in adoption of electronic medical
      record (EMR) systems in the recent years. However, physicians' progress in using
      these systems has stagnated when measured with maturity scales. While this so
      called ceiling effect has been observed and its consequences described in
      previous studies, there is a paucity of research on the elements that could
      explain such an outcome. We first suggest that in the context of EMR systems we
      are in presence of a "tiered ceiling effect" and then we show why such phenomenon
      occurs. METHODS: We conducted in-depth case studies in three primary care medical
      practices in Canada where physicians had been using EMR systems for 3 years or
      more. A total of 37 semi-structured interviews were conducted with key
      informants: family physicians (about half of the interviews), nurses,
      secretaries, and administrative managers. Additional information was obtained
      through notes taken during observations of users interacting with their EMR
      systems and consultation of relevant documents at each site. We used abductive
      reasoning to infer explanations of the observed phenomenon by going back and
      forth between the case data and conceptual insights. RESULTS: Our analysis shows
      that a ceiling effect has taken place in the three clinics. We identified a set
      of conditions preventing the users from overcoming the ceiling. In adopting an
      EMR system, all three clinics essentially sought improved operational efficiency.
      This had an influence on the criteria used to assess the systems available on the
      market and eventually led to the adoption of a system that met the specified
      criteria without being optimal. Later, training sessions focussed on basic
      functionalities that minimally disturbed physicians' habits while helping their
      medical practices become more efficient. Satisfied with the outcome of their
      system use, physicians were likely to ignore more advanced EMR system
      functionalities. This was because their knowledge about EMR systems came almost
      exclusively from a single source of information: their EMR system vendors. This
      knowledge took the form of interpretations of what the innovation was (know
      what), with little consideration of the rationales for innovation adoption (know
      why) or hands-on strategies for adopting, implementing and assimilating the
      innovation in the organization (know-how). CONCLUSIONS: This paper provides a
      holistic view of the technological innovation process in primary care and
      contends that limited learning, satisficing behaviours and organizational inertia
      are important factors leading to the ceiling effect frequently experienced in the
      EMR system assimilation phase.

PMID- 28427406
TI  - Latent membrane protein 1 (LMP1) expression in Hodgkin lymphoma and its
      correlation with clinical and histologic parameters.
AB  - BACKGROUND: Hodgkin lymphoma is one of the most prevalent lymphoproliferative
      disorders in Pakistan; however, no risk factors for this disease have yet to be
      established in our population. Epstein-Barr virus (EBV) is a well-known risk
      factor for Hodgkin lymphoma in endemic regions of the world; however, frequency
      of its association in our population has not been widely studied. Latent membrane
      protein 1 (LMP1) expression by immunohistochemistry (IHC) is a surrogate marker
      of EBV in Hodgkin lymphoma. Therefore, we aimed to evaluate the frequency of
      expression of LMP1 in cases of Hodgkin lymphoma at our institute and its
      correlation with other clinical and histologic parameters. METHODS: The study
      included 66 cases of Hodgkin lymphoma diagnosed at Liaquat National Hospital over
      a duration of 2 years from January 2014 to December 2015. The slides and blocks
      of all cases were retrieved, and representative blocks were selected for LMP1 by
      IHC. LMP1 expression of >10% of cells was considered as positive expression and
      correlated with histologic subtypes and clinical parameters like age, gender, and
      site of involvement. RESULTS: The mean age of patients was 35.11 (+20.22). LMP1
      expression was found in 68.1% (45/66) of cases of Hodgkin lymphoma. Mean age of
      the patients with LMP1 expression was 32.04 (+21.02). LMP1 expression was found
      in 40% cases of lymphocyte-rich, 66.7% of lymphocyte-depleted, 73.9% of mixed
      cellularity, 66.7% of nodular sclerosis, and 73.7% of classic Hodgkin lymphoma,
      NOS. No significant correlation of LMP1 expression with any clinical or
      histological parameter could be established in our studied patient population.
      CONCLUSIONS: A high frequency of expression of LMP1 is seen in cases of Hodgkin
      lymphoma at our setup comparable to endemic regions of the world; therefore,
      preventive and treatment protocols should be designed accordingly.

PMID- 28427407
TI  - Constructive eHealth evaluation: lessons from evaluation of EHR development in 4
      Danish hospitals.
AB  - BACKGROUND: Information and communication sources in the healthcare sector are
      replaced with new eHealth technologies. This has led to problems arising from the
      lack of awareness of the importance of end-user involvement in eHealth
      development and of the difficulties caused by using traditional summative
      evaluation methods. The Constructive eHealth evaluation method (CeHEM) provides a
      solution to these problems by offering an evaluation framework for supporting and
      facilitating end-user involvement during all phases of eHealth development. The
      aim of this paper is to support this process by sharing experiences of the
      eHealth evaluation method used in the introduction of electronic health records
      (EHR) in the North Denmark Region of Denmark. It is the first time the fully
      developed method and the experiences on using the CeHEM in all five phases of a
      full lifecycle framework is presented. METHODS: A case study evaluation of the
      EHR development process in the North Denmark Region was conducted from 2004 to
      2010. The population consisted of clinicians, IT professionals, administrators,
      and vendors. The study involved 4 hospitals in the region. Data were collected
      using questionnaires, observations, interviews, and insight gathered from
      relevant documents. RESULTS: The evaluation showed a need for a) Early
      involvement of clinicians, b) The best possible representation of clinicians, and
      c) Workload reduction for those involved. The consequences of not providing this
      were a lack of ownership of decisions and negative attitudes towards the clinical
      benefits related to these decisions. Further, the result disclosed that by
      following the above recommendations, and by providing feedback to the 4 actor
      groups, the physicians' involvement was improved. As a result they took ownership
      of decisions and gained a positive attitude to the clinical benefits.
      CONCLUSIONS: The CeHEM has proven successful in formative evaluation of EHR
      development and can point at important issues that need to be taken care of by
      management. The method provides a framework that takes care of feedback and
      learning during eHealth development. It can thus support successful eHealth
      development in a broader context while building on a well-known success factor:
      end-user involvement in eHealth development.

PMID- 28427408
TI  - Time-averaged simulated microgravity (taSMG) inhibits proliferation of lymphoma
      cells, L-540 and HDLM-2, using a 3D clinostat.
AB  - BACKGROUND: Gravity is omnipresent on Earth; however, humans in space, such as
      astronauts at the International Space Station, experience microgravity. Long-term
      exposure to microgravity is considered to elicit physiological changes, such as
      muscle atrophy, in the human body. In addition, certain types of cancer cells
      demonstrate inhibited proliferation under condition of time-averaged simulated
      microgravity (taSMG). However, the response of human Hodgkin's lymphoma cancer
      cells to reduced gravity, and the associated physiological changes in these
      cells, have not been elucidated. METHODS: In this study, the proliferation of
      human Hodgkin's lymphoma cancer cells (L-540 and HDLM-2) under taSMG condition
      (<10-3 G, 1 G is defined as 9.8 m/s2) was studied using a 3D clinostat. Normal
      human dermal fibroblast (HDF) was proliferated in the same condition as a control
      group. For the development of 3D clinostat, two motors were used to actuate the
      frames. Electrical wires for power supply and communication were connected via
      slip ring. For symmetrical path of gravitational vector, optimal angular
      velocities of the motors were found using simulation results. Under the condition
      of taSMG implemented by the 3D clinostat, proliferation of the cells was observed
      for 3 days. RESULTS: The results indicated that proliferation of these cancer
      cells was significantly (p < 0.0005) inhibited under taSMG, whereas proliferation
      of normal HDF cells was not affected. CONCLUSIONS: Findings in this study could
      be significantly valuable in developing novel strategies for selective killing of
      cancer cells such as lymphoma.

PMID- 28427409
TI  - Efficacies of DHA-PPQ and AS/SP in patients with uncomplicated Plasmodium
      falciparum malaria in an area of an unstable seasonal transmission in Sudan.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT), together with other
      control measures, have reduced the burden of falciparum malaria in sub-Saharan
      countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction
      in mortality due to falciparum malaria. However, emergence of resistance to the
      first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created
      new challenges to the control of malaria in Sudan. A search for an alternative
      drug of choice for treating uncomplicated malaria has become inevitable. The
      objective of this study was to evaluate the therapeutic efficacies of
      dihydroartemisinin/piperaquine (DHA-PPQ) and AS/SP in an area of unstable
      transmission in Blue Nile State, Sudan in 2015-16. METHODS: A total of 148
      patients with uncomplicated malaria were recruited in the study from November
      2015 to end of January 2016. Seventy-five patients received DHA-PPQ while 73
      received AS/SP. Patients were monitored for clinical and parasitological outcomes
      following the standard WHO protocol for a period of 42 days for DHA-PPQ and 28
      days for AS/SP; nested PCR (nPCR) was performed to confirm parasite re-appearance
      from day 7 onwards. RESULTS: Fifty-five patients completed the DHA-PPQ arm
      protocol with success cure rate of 98.2% (95% CI 90.3-100%) and one late clinical
      failure 1.8% (95% CI 0.0-9.7%). The AS/SP showed adequate clinical and
      parasitological response (ACPR) of 83.6% (95% CI 71.9-91.8%), early treatment
      failure was 1.6% (95% CI 0.0-8.8%) and late parasitological failure (LPF) was
      14.8% (95% CI 7-26.2%). The respective PCR uncorrected LPF was 20%. CONCLUSION:
      DHA-PPQ is an efficacious ACT and candidate for replacement of first-line
      treatment in Sudan while AS/SP showed high treatment failure rate and must be
      replaced.

PMID- 28427410
TI  - Long-term follow-up after stereotactic radiosurgery of intracanalicular acoustic
      neurinoma.
AB  - BACKGROUND: The management of solely intracanalicular acoustic neurinoma (iAN)
      includes observation, microsurgical resection and radiation therapy. Treatment
      goals are long-term tumor control, hearing preservation and concurrently low side
      effects. Stereotactic radiosurgery (SRS) has evolved as an alternative first-line
      treatment for small AN. Here we report about the long-term follow-up of a unique
      cohort of patients with iAN after LINAC or Cyberknife(r) based SRS. METHODS: In
      this single center retrospective analysis, we included all patients with iAN who
      underwent single session LINAC or Cyberknife(r) based SRS between 1993 and 2015,
      and who had a minimum follow-up period of six weeks. Patient data were analyzed
      in terms of radiological and clinical tumor control (no further treatment
      necessary), subjective preservation of serviceable hearing, objective change in
      pure tone averages (PTA), and adverse events rated by the Common Terminology
      Criteria for Adverse Events (CTCAE; v4.03). RESULTS: Forty-nine patients (f/m =
      21/28, median age 54 +/- 12, range 20-77 years) were identified. Mean tumor
      volumes were 0.24 +/- 0.12 cm3 (range, 0.1-0.68 cm3), the mean marginal dose was
      12.6 +/- 0.6 Gy (range, 11.0-14.0 Gy) and the prescription isodose was 75 +/-
      7.4% (range, 47-86%). Mean follow-up time was 65 months (range, 4-239 months).
      Radiological tumor control was 100% during further follow-up. 17 (35%) out of 49
      patients had lost serviceable hearing prior to SRS. Those with preserved
      serviceable hearing remained stable in 78% (n = 25/32) at the last follow-up
      (LFU). The median PTA (n = 16) increased from 25.6 dB prior to SRS to 43.8 dB at
      LFU. Mild adverse events were observed temporarily in two patients (4%): one with
      CTCAE grade 1 facial nerve disorder after 3 months, resolving three months later,
      and one with CTCAE grade 2 facial muscle weakness resolving after 12 months.
      Three patients described permanent mild symptoms CTCAE grade 1 without limiting
      daily life (facial weakness n = 1, vertigo n = 2). CONCLUSION: SRS for iAN shows
      long-term reliable tumor control with a high rate of hearing preservation without
      considerable permanent side effects, and can be proposed as a safe and effective
      treatment alternative to microsurgical resection.

PMID- 28427411
TI  - Tendon-motion tracking in an ultrasound image sequence using optical-flow-based
      block matching.
AB  - BACKGROUND: Tendon motion, which is commonly observed using ultrasound imaging,
      is one of the most important features used in tendinopathy diagnosis. However,
      speckle noise and out-of-plane issues make the tracking process difficult. Manual
      tracking is usually time consuming and often yields inconsistent results between
      users. METHODS: To automatically track tendon motion in ultrasound images, we
      developed a new method that combines the advantages of optical flow and multi
      kernel block matching. For every pair of adjacent image frames, the optical flow
      is computed and used to estimate the accumulated displacement. The proposed
      method selects the frame interval adaptively based on this displacement. Multi
      kernel block matching is then computed on the two selected frames, and, to reduce
      tracking errors, the detailed displacements of the frames in between are
      interpolated based on the optical flow results. RESULTS: In the experiments,
      cadaver data were used to evaluate the tracking results. The mean absolute error
      was less than 0.05 mm. The proposed method also tracked the motion of tendons in
      vivo, which provides useful information for clinical diagnosis. CONCLUSION: The
      proposed method provides a new index for adaptively determining the frame
      interval. Compared with other methods, the proposed method yields tracking
      results that are significantly more accurate.

PMID- 28427412
TI  - Lack of interleukin-13 receptor alpha1 delays the loss of dopaminergic neurons
      during chronic stress.
AB  - BACKGROUND: The majority of Parkinson's disease (PD) cases are sporadic and
      idiopathic suggesting that this neurodegenerative disorder is the result of both
      environmental and genetic factors. Stress and neuroinflammation are among the
      factors being investigated for their possible contributions to PD. Experiments in
      rodents showed that severe chronic stress can reduce the number of dopaminergic
      neurons in the substantia nigra pars compacta (SNc); the same cells that are lost
      in PD. These actions are at least in part mediated by increased oxidative stress.
      Here, we tested the hypothesis that the interleukin-13 receptor alpha 1 (IL
      13Ralpha1), a cytokine receptor whose activation increases the vulnerability of
      dopaminergic neurons to oxidative damage, participates in the stress-dependent
      damage of these neurons. METHODS: Mice were subject to daily sessions of 8 h
      (acute) stress for 16 weeks (5 days a week), a procedure previously showed to
      induce loss of dopaminergic neurons in the SNc. The source and the kinetics of
      interleukin-13 (IL-13), the endogenous ligand of IL-13Ralpha1, were evaluated 0,
      1, 3, 6, and 8 h and at 16 weeks of stress. Identification of IL-13 producing
      cell-type was performed by immunofluorescent and by in situ hybridization
      experiments. Markers of oxidative stress, microglia activation, and the number of
      dopaminergic neurons in IL-13Ralpha1 knock-out animals (Il13ra1 Y/ - ) and their
      wild-type littermates (Il13ra1 Y/+ ) were evaluated at 16 weeks of stress and at
      20 weeks, following a 4 week non-stressed period and compared to non-stressed
      mice. RESULTS: IL-13 was expressed in microglial cells within the SN and in a
      fraction of the tyrosine hydroxylase-positive neurons in the SNc. IL-13 levels
      were elevated during daily stress and peaked at 6 h. 16 weeks of chronic
      restraint stress significantly reduced the number of SNc dopaminergic neurons in
      Il13ra1 Y/+ mice. Neuronal loss at 16 weeks was significantly lower in Il13ra1 Y/
      mice. However, the loss of dopaminergic neurons measured at 20 weeks, after 4
      weeks of non-stress following the 16 weeks of stress, was similar in Il13ra1 Y/+
      and Il13ra1 Y/- mice. CONCLUSIONS: IL-13, a cytokine previously demonstrated to
      increase the susceptibility of SNc dopaminergic neurons to oxidative stress, is
      elevated in the SN by restraint stress. Lack of IL-13Ralpha1 did not prevent nor
      halted but delayed neuronal loss in the mouse model of chronic restraint stress.
      IL-13/IL-13Ralpha1 may represent a target to reduce the rate of DA neuronal loss
      that can occur during severe chronic restraint stress.

PMID- 28427413
TI  - Adiponectin levels in the serum and cerebrospinal fluid of amyotrophic lateral
      sclerosis patients: possible influence on neuroinflammation?
AB  - BACKGROUND: Adiponectin (APN) is a key player in energy homeostasis strictly
      associated with cerebrovascular and neurodegenerative diseases. Since APN also
      belongs to anti-inflammatory-acting adipokines and may influence both
      neuroinflammation and neurodegenerative processes, we decided to study the APN
      levels in amyotrophic lateral sclerosis (ALS) and other neurodegenerative
      diseases. METHODS: We assessed APN levels by ELISA immunoassay in both the serum
      and cerebrospinal fluid of a cohort of familial and sporadic ALS patients,
      characterized by normal body mass index and absence of dysautonomic symptoms. The
      screening of serum APN levels was also performed in patients affected by other
      neurological disorders, including fronto-temporal dementia (FTD) patients. Means
      were compared using the non-parametric Wilcoxon test, and Pearson's or Spearman's
      rho was used to assess correlations between variables. RESULTS: In the whole ALS
      group, serum APN levels were not different when compared to the age- and sex
      matched control group (CTR), but a gender-specific analysis enlightened a
      significant opposite APN trend between ALS males, characterized by lower values
      (ALS 9.8 +/- 5.2 vs. CTR 15 +/- 9.7 MUg/ml), and ALS females, showing higher
      amounts (ALS 26.5 +/- 11.6 vs. CTR 14.6 +/- 5.2 MUg/ml). This sex-linked
      difference was significantly enhanced in familial ALS cases (p <= 0.01). The APN
      levels in ALS cerebrospinal fluids were unrelated to serum values and not linked
      to sex and/or familiarity of the disease. Finally, the screening of serum APN
      levels in patients affected by other neurological disorders revealed the highest
      serum values in FTD patients. CONCLUSIONS: Opposite serum APN levels are gender
      related in ALS and altered in several neurological disorders, with the highest
      values in FTD, which shares with ALS several overlapping and neuropathological
      features. Further investigations are needed to clarify the possible involvement
      of APN in neuroinflammation and neurodegeneration. Possible involvement of APN in
      neuroinflammatory neurodegenerative diseases.

PMID- 28427414
TI  - Observational study of Interleukin-21 (IL-21) does not distinguish Kawasaki
      disease from other causes of fever in children.
AB  - BACKGROUND: Kawasaki disease (KD) is a febrile childhood vasculitis of unknown
      etiology. The diagnosis is highly concerning as over a quarter of children who
      fail to receive timely treatment with intravenous immunoglobulin (IVIG) will
      develop coronary aneurysms. Diagnosis relies on proper symptomatology and is
      supported by non-specific markers of inflammation. Previous studies have
      identified elevated plasma levels of interleukin-21 (IL-21) as a sensitive and
      specific biomarker in KD. The aim of this study is to assess the validity of IL
      21 as a diagnostic biomarker for KD in febrile children in North America.
      METHODS: Plasma samples were collected from children who presented to an urban
      Emergency Department in North America. IL-21 levels were measured using
      commercial ELISA kits in 12 KD versus 60 controls subjects. RESULTS: Our study
      shows that IL-21 levels were non-specifically elevated across all febrile
      children, irrespective of KD diagnosis. Length of fever prior to sample
      collection does not correlate with IL-21 levels. Other inflammatory markers and
      laboratory values were also compared to IL-21 and show no significant
      correlation. CONCLUSIONS: Since IL-21 is elevated non-specifically in this
      cohort, our data supports that IL-21 is not an appropriate biomarker for
      diagnosis of KD in North American pediatric populations.

PMID- 28427415
TI  - Insecticide resistance patterns in Uganda and the effect of indoor residual
      spraying with bendiocarb on kdr L1014S frequencies in Anopheles gambiae s.s.
AB  - BACKGROUND: Resistance of malaria vectors to pyrethroid insecticides has been
      attributed to selection pressure from long-lasting insecticidal nets (LLINs),
      indoor residual spraying (IRS), and the use of chemicals in agriculture. The use
      of different classes of insecticides in combination or by rotation has been
      recommended for resistance management. The aim of this study was to understand
      the role of IRS with a carbamate insecticide in management of pyrethroid
      resistance. METHODS: Anopheles mosquitoes were collected from multiple sites in
      nine districts of Uganda (up to five sites per district). Three districts had
      been sprayed with bendiocarb. Phenotypic resistance was determined using standard
      susceptibility tests. Molecular assays were used to determine the frequency of
      resistance mutations. The kdr L1014S homozygote frequency in Anopheles gambiae
      s.s. was used as the outcome measure to test the effects of various factors using
      a logistic regression model. Bendiocarb coverage, annual rainfall, altitude,
      mosquito collection method, LLIN use, LLINs distributed in the previous 5 years,
      household use of agricultural pesticides, and malaria prevalence in children 2-9
      years old were entered as explanatory variables. RESULTS: Tests with pyrethroid
      insecticides showed resistance and suspected resistance levels in all districts
      except Apac (a sprayed district). Bendiocarb resistance was not detected in
      sprayed sites, but was confirmed in one unsprayed site (Soroti). Anopheles
      gambiae s.s. collected from areas sprayed with bendiocarb had significantly less
      kdr homozygosity than those collected from unsprayed areas. Mosquitoes collected
      indoors as adults had significantly higher frequency of kdr homozygotes than
      mosquitoes collected as larvae, possibly indicating selective sampling of
      resistant adults, presumably due to exposure to insecticides inside houses that
      would disproportionately affect susceptible mosquitoes. The effect of LLIN use on
      kdr homozygosity was significantly modified by annual rainfall. In areas
      receiving high rainfall, LLIN use was associated with increased kdr homozygosity
      and this association weakened as rainfall decreased, indicating more frequency of
      exposure to pyrethroids in relatively wet areas with high vector density.
      CONCLUSION: This study suggests that using a carbamate insecticide for IRS in
      areas with high levels of pyrethroid resistance may reduce kdr frequencies in An.
      gambiae s.s.

PMID- 28427416
TI  - Shoulder ultrasonography performed by orthopedic surgeons increases efficiency in
      diagnosis of rotator cuff tears.
AB  - BACKGROUND: Rotator cuff tears are very common and their incidence increases with
      age. Shoulder ultrasonography has recently gained popularity in detecting rotator
      cuff tears because of its efficiency, cost-effectiveness, time-saving, and real
      time nature of the procedure. Well-trained orthopedic surgeons may utilize
      shoulder ultrasonography to diagnose rotator cuff tears. The wait time of
      patients planned to have shoulder MRI (magnetic resonance imaging) to rule in
      rotator cuff tears may decrease after orthopedic surgeon start doing shoulder
      ultrasonography as a screening tool for that. Patients with rotator cuff tears
      may be detected earlier by ultrasonography and have expedited surgical repair.
      The efficacy in determination of rotator cuff tears will also increase. METHODS:
      Patients were retrospectively reviewed from January 2007 to December 2012. They
      were divided into 2 groups: Ultrasound (-) group and the Ultrasound (+) group.
      Age, gender, wait time from outpatient department (OPD) visit to MRI exam, MRI
      exam to operation (OP), and OPD visit to OP, patient number for MRI exam, and
      number of patients who finally had rotator cuff repair within two groups were
      compared. RESULTS: The wait time of OPD visit to OP and MRI to OP in patients who
      received shoulder ultrasonography was significantly less than that in patients
      did not receive shoulder ultrasonography screening. Only 23.8% of the patients
      with a suspected rotator cuff injury undergone arthroscopic rotator cuff repair
      before ultrasonography was applied as a screening tool. The percentage increased
      to 53.6% after orthopedic surgeon started using ultrasonography as a screening
      tool for rotator cuff tears. CONCLUSIONS: Office-based shoulder ultrasound
      examination can reduce the wait time for a shoulder MRI. The efficacy of
      determination of rotator cuff tears will also increase after the introduction of
      shoulder ultrasonography.

PMID- 28427417
TI  - Novel trigenic CACNA1C/DES/MYPN mutations in a family of hypertrophic
      cardiomyopathy with early repolarization and short QT syndrome.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) patients with early repolarization
      (ER) pattern are at higher risk of ventricular arrhythmia, yet the genetic
      background of this situation has not been well investigated. Here we report novel
      trigenic mutations detected in a Chinese family of obstructive HCM with ER and
      short QT syndrome (SQTS). METHODS: Proband and family members underwent detailed
      medical assessments. DNAs were extracted from peripheral blood leukocytes for
      genetic screening with next generation method. The functional characterization of
      the mutation was conducted in TSA201 cells with patch-clamp experiment. RESULTS:
      The proband was a 52-year-old male who had a ER pattern ECG in inferioral-lateral
      leads with atrioventricular block and QTc of 356 ms. He also suffered from severe
      left ventricular hypertrophy and dysfunction. Targeted sequencing revealed
      trigenic mutations: c.700G>A/p.E234K in DES, c.2966G>A/p.R989H in MYPN, and
      c.5918G>C/p.R1973P in CACNA1C. All mutations were also detected in his daughter
      with ER and mild myocardium hypertrophy. The CACNA1C-R1973P mutation caused
      significant reduction (68.4%) of ICa compared to CACNA1C-WT (n = 14 and 14, P <
      0.05). The computer modeling showed that all 3 mutations were highly disease
      causing. The proband received the CRT-D (cardiac resynchronizing therapy)
      implantation, which lowered the left ventricular outflow tract gradient (LVOTG,
      124 mmHg pre vs. 27 mmHg post) and restored the LV function (LVEF 40% pre vs. 63%
      post). CONCLUSIONS: The study reveals a novel CACNA1C mutation underlying the
      unique ER pattern ECGs with SQTS. It also shows the rare trigenic mutations are
      the pathogenic substrates for the complicated clinical manifestation in HCM
      patients.

PMID- 28427418
TI  - Immunity as a predictor of anti-malarial treatment failure: a systematic review.
AB  - BACKGROUND: Naturally acquired immunity can reduce parasitaemia and potentially
      influence anti-malarial treatment outcomes; however, evidence for this in the
      current literature provides conflicted results. The available evidence was
      synthesized to determine and quantify the association between host immunity and
      anti-malarial treatment failure. METHODS: Four databases were searched to
      identify studies investigating malaria antibody levels in patients receiving anti
      malarial treatment for symptomatic malaria with treatment failure recorded
      according to the World Health Organization classification. Odds ratios or hazard
      ratios were extracted or calculated to quantify the association between malarial
      antibody levels and treatment failure, and findings from different studies were
      visualized using forest plots. RESULTS: Eight studies, including patients with
      falciparum malaria treated with mono- and combination therapy of artemisinin
      derivatives, sulfadoxine, pyrimethamine and chloroquine, were identified.
      Reported and calculated effect estimates varied greatly between studies, even
      those assessing the same antigens and treatments. An association between blood
      stage IgG responses and treatment efficacy was observed. The greatest magnitudes
      of effect were observed for artemisinin [OR/HR (95% CI) range 0.02 (0.00, 0.45)
      1.08 (0.57, 2.06)] and chloroquine [0.24 (0.04, 1.37)-0.32 (0.05, 1.96)]
      treatments, and larger magnitudes of effect were observed for variant surface
      antigen responses [0.02 (0.00, 0.45)-1.92 (0.94, 3.91)] when compared with
      merozoite specific responses [0.24 (0.04, 1.37)-2.83 (1.13, 7.09)]. CONCLUSIONS:
      Naturally acquired malarial immunity is associated with reduced anti-malarial
      treatment failure in malaria endemic populations. Anti-malarial IgG effects
      treatment outcome differently for different anti-malarial drugs and antigen
      targets, and had the greatest impact during treatment with the current first-line
      treatments, the artemisinins. This has implications for the assessment of the
      therapeutic efficacy of anti-malarials, particularly in the context of emerging
      artemisinin resistance.

PMID- 28427419
TI  - TNF-alpha promotes extracellular vesicle release in mouse astrocytes through
      glutaminase.
AB  - BACKGROUND: Extracellular vesicles (EVs) are membrane-contained vesicles shed
      from cells. EVs contain proteins, lipids, and nucleotides, all of which play
      important roles in intercellular communication. The release of EVs is known to
      increase during neuroinflammation. Glutaminase, a mitochondrial enzyme that
      converts glutamine to glutamate, has been implicated in the biogenesis of EVs. We
      have previously demonstrated that TNF-alpha promotes glutaminase expression in
      neurons. However, the expression and the functionality of glutaminase in
      astrocytes during neuroinflammation remain unknown. We posit that TNF-alpha can
      promote the release of EVs in astrocytes through upregulation of glutaminase
      expression. RESULTS: Release of EVs, which was demonstrated by electron
      microscopy, nanoparticle tracking analysis (NTA), and Western Blot, increased in
      mouse astrocytes when treated with TNF-alpha. Furthermore, TNF-alpha treatment
      significantly upregulated protein levels of glutaminase and increased the
      production of glutamate, suggesting that glutaminase activity is increased after
      TNF-alpha treatment. Interestingly, pretreatment with a glutaminase inhibitor
      blocked TNF-alpha-mediated generation of reactive oxygen species in astrocytes,
      which indicates that glutaminase activity contributes to stress in astrocytes
      during neuroinflammation. TNF-alpha-mediated increased release of EVs can be
      blocked by either the glutaminase inhibitor, antioxidant N-acetyl-L-cysteine, or
      genetic knockout of glutaminase, suggesting that glutaminase plays an important
      role in astrocyte EV release during neuroinflammation. CONCLUSIONS: These
      findings suggest that glutaminase is an important metabolic factor controlling EV
      release from astrocytes during neuroinflammation.

PMID- 28427420
TI  - Comparative study of single-center patients with thyroid metastases from
      colorectal cancer and previously reported cases in the literature.
AB  - BACKGROUND: Thyroid metastases from colorectal cancer (CRC) are rare, both in
      clinical practice and in the literature; hence, their diagnosis, appropriate
      treatment, and prognostic factors require further investigations. METHODS: A
      retrospective analysis was performed for four cases of thyroid metastases from
      CRC, treated in our center between January 2005 and December 2015, and the
      relevant literature was searched using PubMed, resulting in the identification of
      17 patients with detailed information available. The clinical data and follow-up
      information of our patients and the previously reported cases were collected and
      compared. RESULTS: The median age of the 21 patients was 59 years (44.5 and 66
      years for our patients and the previously reported cases, respectively). Fifteen
      (71.4%) primary tumors were distributed throughout the distal colon or rectum
      (75% [3/4] in our center and 70.5% [12/17] in the previously reported cases).
      According to our analysis, we found that 81.0% of patients (17/21) showed
      concomitant lung metastasis. Among them, all four patients in our center showed
      lung metastasis, and 75% (3/4) developed thyroid metastases after the lung
      metastasis. In the previously reported cases, the corresponding proportions were
      76.5 and 76.5% (13/17) of patients, respectively. The median time after primary
      tumor diagnosis to thyroid metastasis development was 28 months (26 months in our
      center and 35 months in the previously reported cases). One patient with advanced
      CRC in our center died 5 months after the thyroid metastasis was identified,
      while the remaining three patients are currently alive (longest follow-up time,
      27 months). The median survival time after thyroid metastasis during 3 years of
      follow-up of the previously reported 17 patients was 12 months. There was no
      difference in the overall survival between patients treated non-surgically (8/21)
      and patients undergoing thyroidectomy alone or thyroidectomy with adjuvant
      therapy (13/21) (p = 0.388). In addition, we found that the overall survival of
      the patients whose other metastases were treated with radical treatment was
      superior to that in those treated with palliative treatment (p = 0.022).
      CONCLUSIONS: Thyroid metastases from CRC are rare in clinical practice and are a
      manifestation of advanced CRC. The prognosis of patients with thyroid metastases
      from CRC is related to various factors, including the grade of malignancy of the
      primary lesion, the presence of other metastases, and whether the metastases are
      timely diagnosed and a radical treatment strategy is employed.

PMID- 28427422
TI  - Differences in muscle activity and temporal step parameters between Lokomat
      guided walking and treadmill walking in post-stroke hemiparetic patients and
      healthy walkers.
AB  - BACKGROUND: The Lokomat is a robotic exoskeleton that can be used to train gait
      function in hemiparetic stroke. To purposefully employ the Lokomat for training,
      it is important to understand (1) how Lokomat guided walking affects muscle
      activity following stroke and how these effects differ between patients and
      healthy walkers, (2) how abnormalities in the muscle activity of patients are
      modulated through Lokomat guided gait, and (3) how temporal step characteristics
      of patients were modulated during Lokomat guided walking. METHODS: Ten
      hemiparetic stroke patients (>3 months post-stroke) and ten healthy age-matched
      controls walked on the treadmill and in the Lokomat (guidance force 50%, no
      bodyweight support) at matched speeds (0.56 m/s). Electromyography was used to
      record the activity of Gluteus Medius, Biceps Femoris, Vastus Lateralis, Medial
      Gastrocnemius and Tibialis Anterior, bilaterally in patients and of the dominant
      leg in healthy walkers. Pressure sensors placed in the footwear were used to
      determine relative durations of the first double support and the single support
      phases. RESULTS: Overall, Lokomat guided walking was associated with a general
      lowering of muscle activity compared to treadmill walking, in patients as well as
      healthy walkers. The nature of these effects differed between groups for specific
      muscles, in that reductions in patients were larger if muscles were overly active
      during treadmill walking (unaffected Biceps Femoris and Gluteus Medius, affected
      Biceps Femoris and Vastus Lateralis), and smaller if activity was already
      abnormally low (affected Medial Gastrocnemius). Also, Lokomat guided walking was
      associated with a decrease in asymmetry in the relative duration of the single
      support phase. CONCLUSIONS: In stroke patients, Lokomat guided walking results in
      a general reduction of muscle activity, that affects epochs of overactivity and
      epochs of reduced activity in a similar fashion. These findings should be taken
      into account when considering the clinical potential of the Lokomat training
      environment in stroke, and may inform further developments in the design of
      robotic gait trainers.

PMID- 28427421
TI  - Cerebrospinal fluid (CSF) biomarkers of iron status are associated with CSF viral
      load, antiretroviral therapy, and demographic factors in HIV-infected adults.
AB  - BACKGROUND: HIV-associated neurocognitive disorder (HAND) remains common, despite
      antiretroviral therapy (ART). HIV dysregulates iron metabolism, but cerebrospinal
      fluid (CSF) levels of iron and iron-transport proteins in HIV-infected (HIV+)
      persons are largely unknown. The objectives of this study were to characterize
      CSF iron-related biomarkers in HIV+ adults and explore their relationships to
      known predictors of HAND. METHODS: We quantified total iron, transferrin and
      heavy-chain (H)-ferritin by immunoassay in CSF sampled by lumbar puncture in 403
      HIV+ participants in a multi-center, observational study and evaluated biomarker
      associations with demographic and HIV-related correlates of HAND [e.g., age, sex,
      self-reported race/ethnicity, ART, and detectable plasma virus and CSF viral load
      (VL)] by multivariable regression. In a subset (N = 110) with existing CSF: serum
      albumin (QAlb) measurements, QAlb and comorbidity severity were also included as
      covariates to account for variability in the blood-CSF-barrier. RESULTS: Among
      403 individuals (median age 43 years, 19% women, 56% non-Whites, median nadir
      CD4+ T cell count 180 cells/uL, 46% with undetectable plasma virus), men had 25%
      higher CSF transferrin (median 18.1 vs. 14.5 ug/mL), and 71% higher H-ferritin
      (median 2.9 vs. 1.7 ng/mL) than women (both p-values <=0.01). CSF iron was 41%
      higher in self-reported Hispanics and 27% higher in (non-Hispanic) Whites than in
      (non-Hispanic) Blacks (median 5.2 and 4.7 ug/dL in Hispanics and Whites,
      respectively, vs. 3.7 ug/dL in Blacks, both p <= 0.01); these findings persisted
      after adjustment for age, sex, and HIV-specific factors. Median H-ferritin was
      25% higher (p < 0.05), and transferrin 14% higher (p = 0.06), in Whites than
      Blacks. Transferrin and H-ferritin were 33 and 50% higher, respectively, in older
      (age > 50 years) than in younger persons (age <= 35 years; both p < 0.01), but
      these findings lost statistical significance in subset analyses that adjusted for
      QAlb and comorbidity. After these additional adjustments, associations were
      observed for CSF iron and transferrin with race/ethnicity as well as CSF VL, for
      transferrin with sex and ART, and for H-ferritin with plasma virus detectability
      and significant comorbidity (all p < 0.05). CONCLUSIONS: CSF iron biomarkers are
      associated with demographic factors, ART, and CSF VL in HIV+ adults. Future
      studies should investigate a role for CNS iron dysregulation, to which an altered
      blood-CSF barrier may contribute, in HAND.

PMID- 28427423
TI  - Analysis of inequality in maternal and child health outcomes and mortality from
      2000 to 2013 in China.
AB  - BACKGROUND: Inequality in maternal and child health seriously hinders the overall
      improvement of health, which is a concern in both the United Nations Sustainable
      Development Goals (SDGs) and Healthy China 2030. However, research on the
      equality of maternal and child health is scarce. This study longitudinally
      assessed the equality trends in China's maternal and child health outcomes from
      2000 to 2013 based on place of residence and gender to improve the fairness of
      domestic maternal and child health. METHODS: Data on China's maternal and child
      health monitoring reports were collected from 2000 to 2013. Horizontal and
      vertical monitoring were performed on the following maternal and child health
      outcome indicators: incidence of birth defects (IBD), maternal mortality rate
      (MMR), under 5 mortality rate (U5MR) and neonatal mortality rate (NMR). The newly
      developed HD*Calc software by the World Health Organization (WHO) was employed as
      a tool for the health inequality assessment. The between group variance (BGV) and
      the Theil index (T) were used to measure disparity between different population
      groups, and the Slope index was used to analyse the BGV and T trends. RESULTS:
      The disparity in the MMR, U5MR and NMR for the different places of residence
      (urban and rural) improved over time. The BGV (Slope BGV = -32.24) and T (Slope T
      = -7.87) of MMR declined the fastest. The gender differences in the U5MR (Slope
      BGV = -0.06, Slope T = -0.21) and the NMR (Slope BGV = -0.01, Slope T = 0.23)
      were relatively stable, but the IBD disparity still showed an upward trend in
      both the place of residence and gender strata. A decline in urban-rural
      differences in the cause of maternal death was found for obstetric bleeding
      (Slope BGV = -14.61, Slope T = -20.84). Improvements were seen in the urban-rural
      disparity in premature birth and being underweight (PBU) in children under 5
      years of age. Although diarrhoea and pneumonia decreased in the U5MR, no obvious
      gender-based trend in the causes of death was observed. CONCLUSION: We found
      improvement in the disparity of maternal and child health outcomes in China.
      However, the improvements still do not meet the requirements proposed by the
      Healthy China 2030 strategy, particularly regarding the rise in the IBD levels
      and the decline in equality. This study suggests starting with maternal and child
      health services and focusing on the disparity in the causes of death in both the
      place of residence and gender strata. Placing an emphasis on health services may
      encourage the recovery of the premarital check and measures such as prenatal and
      postnatal examinations to improve equality.

PMID- 28427424
TI  - Microglial depletion alters the brain neuroimmune response to acute binge ethanol
      withdrawal.
AB  - BACKGROUND: Recent studies have implicated microglia-the resident immune cells of
      the brain-in the pathophysiology of alcoholism. Indeed, post-mortem alcoholic
      brains show increased microglial markers and increased immune gene expression;
      however, the effects of ethanol on microglial functioning and how this impacts
      the brain remain unclear. In this present study, we investigate the effects of
      acute binge ethanol on microglia and how microglial depletion changes the brain
      neuroimmune response to acute binge ethanol withdrawal. METHODS: C57BL/6J mice
      were treated intragastrically with acute binge ethanol for time course and dose
      response studies. Cultured mouse BV2 microglia-like cells were treated with
      ethanol in vitro for time course studies. Mice were also administered the colony
      stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia from
      the brain. These mice were subsequently treated with acute binge ethanol and
      sacrificed during withdrawal. Brain and BV2 mRNA were isolated and assessed using
      RT-PCR to examine expression of microglial and neuroimmune genes. RESULTS: Acute
      binge ethanol biphasically changed microglial (e.g., Iba1, CD68) gene expression,
      with initial decreases during intoxication and subsequent increases during
      withdrawal. Acute ethanol withdrawal dose dependently increased neuroimmune gene
      (e.g., TNFalpha, Ccl2, IL-1ra, IL-4) expression beginning at high doses. BV2
      cells showed biphasic changes in pro-inflammatory (e.g., TNFalpha, Ccl2) gene
      expression following ethanol treatment in vitro. Administration of PLX5622
      depleted microglia from the brains of mice. Although some neuroimmune genes were
      reduced by microglial depletion, many others were unchanged. Microglial depletion
      blunted pro-inflammatory (e.g., TNFalpha, Ccl2) gene expression and enhanced anti
      inflammatory (e.g., IL-1ra, IL-4) gene expression during acute binge ethanol
      withdrawal. CONCLUSIONS: These studies find acute binge ethanol withdrawal
      increases microglial and neuroimmune gene expression. Ethanol exposure also
      increases microglial pro-inflammatory gene expression in vitro. Furthermore,
      microglial depletion decreases expression of microglia-specific genes but has
      little effect on expression of many other neuroimmune signaling genes. Microglial
      depletion blunted the acute binge ethanol withdrawal induction of pro
      inflammatory genes and enhanced induction of anti-inflammatory genes. These
      findings indicate microglia impact the brain response to acute binge ethanol
      withdrawal.

PMID- 28427425
TI  - Impact of lymphocyte differential count > 15% in BALF on the mortality of
      patients with acute exacerbation of chronic fibrosing idiopathic interstitial
      pneumonia.
AB  - BACKGROUND: Chronic fibrosing idiopathic interstitial pneumonia (CFIIP) has a
      potential risk of acute exacerbation (AE). However, the usefulness of cellular
      analysis of bronchoalveolar lavage fluid (BALF) has never been evaluated. This
      study aimed to evaluate the impact of the lymphocyte differential count > 15% in
      BALF on the mortality of patients with AE of CFIIP. METHODS: We retrospectively
      analysed 37 patients with AE of CFIIP who underwent BAL on admission. Patients
      were divided into two groups: one group consisting of those with a lymphocyte
      differential count > 15% and the other consisting of those with a lymphocyte
      differential count <= 15%. We compared the 90-day mortality between the two
      groups as the primary outcome, using the two-tailed log-rank test. RESULTS: The
      median follow-up duration was 6.9 months. Twenty-four patients had a lymphocyte
      differential count > 15%. The 90-day mortality was significantly higher in the
      group with a lymphocyte differential count <= 15% than in the group with a
      lymphocyte differential count > 15% (long rank test, p = 0.003). In the
      multivariate analysis a lymphocyte differential count > 15% was shown to be an
      independent favourable prognostic factor for 90-day mortality (HR: 0.125; 95% CI:
      0.0247-0.589; p = 0.009). CONCLUSIONS: A lymphocyte differential count > 15% in
      BALF may be associated with favourable outcomes in patients with AE of CFIIP.

PMID- 28427426
TI  - The development and validation of an instrument to measure the quality of health
      research reports in the lay media.
AB  - BACKGROUND: The media serves as an important link between medical research, as
      reported in scholarly sources, and the public and has the potential to act as a
      powerful tool to improve public health. However, concerns about the reliability
      of health research reports have been raised. Tools to monitor the quality of
      health research reporting in the media are needed to identify areas of weakness
      in health research reporting and to subsequently work towards the efficient use
      of the lay media as a public health tool through which the public's health
      behaviors can be improved. METHODS: We developed the Quality Index for health
      related Media Reports (QIMR) as a tool to monitor the quality of health research
      reports in the lay media. The tool was developed according to themes generated
      from interviews with health journalists and researchers. Item and domain
      characteristics and scale reliability were assessed. The scale was correlated
      with a global quality assessment score and media report word count to provide
      evidence towards its construct validity. RESULTS: The items and domains of the
      QIMR demonstrated acceptable validity and reliability. Items from the 'validity'
      domain were negatively skewed, suggesting possible floor effect. These items were
      not eliminated due to acceptable content and face validity. QIMR total scores
      produced a strong correlation with raters' global assessment and a moderate
      correlation with media report word count, providing evidence towards the
      construct validity of the instrument. CONCLUSIONS: The results of this
      investigation indicate that QIMR can adequately measure the quality of health
      research reports, with acceptable reliability and validity.

PMID- 28427427
TI  - Association between the ossific nucleus and osteonecrosis in treating
      developmental dysplasia of the Hip: updated meta-analysis.
AB  - BACKGROUND: A meta-analysis concluded that there was no effect of the femoral
      head ossification and the incidence of osteonecrosis in the treatment of
      developmental dysplasia of the hip (DDH), unless only osteonecrosis grades II-IV
      were considered. The meta-analysis, limited due to the small number of studies
      available at that time, identified a need for an update as further research
      emerges. We observed a trend in recent years towards delaying treatment of DDH in
      the absence of an ossified nucleus. Numerous new publications on this topic
      encouraged us to update the 2009 meta-analysis. METHODS: We performed a
      systematic review of the literature from 1967 to 2016 and included studies that
      reported on the treatment of DDH, the ossific nucleus and osteonecrosis. Two
      independent reviewers evaluated all articles. We performed a meta-analysis with
      the main outcome defined as the development of osteonecrosis of the femoral head
      at least two years after closed or open reduction. RESULTS: Of four prospective
      and ten retrospective studies included in the systematic review, 11 studies
      (1,021 hips) met the inclusion criteria for the meta-analysis. There was no
      significant effect of the ossific nucleus on the development of all grades of
      osteonecrosis (relative risk, 0.88; 95% confidence interval, 0.56-1.41) or
      osteonecrosis grades II-IV (0.67; 0.41-1.08). In closed reductions, the ossific
      nucleus halved the risk for developing osteonecrosis grades II-IV (0.50; 0.26
      0.94). CONCLUSIONS: Based on current evidence there does not appear to be a
      protective effect of the ossific nucleus on the development of osteonecrosis. In
      contrast to the previous meta-analysis, this update demonstrates that this
      remains the case irrespective of the grade of osteonecrosis considered relevant.
      This updated meta-analysis is based on twice as many studies with a higher
      quality of evidence.

PMID- 28427428
TI  - Quality issues with malaria rapid diagnostic test accessories and buffer
      packaging: findings from a 5-country private sector project in Africa.
AB  - BACKGROUND: Use of antigen-detecting malaria rapid diagnostic tests (RDTs) has
      increased exponentially over the last decade. WHO's Global Malaria Programme,
      FIND, and other collaborators have established a quality assurance scheme to
      guide product selection, lot verification, transport, storage, and training
      procedures. Recent concerns over the quality of buffer packaging and test
      accessories suggest a need to include these items in product assessments. This
      paper describes quality problems with buffer and accessories encountered in a
      project promoting private sector RDT use in five African countries and suggests
      steps to avoid or more rapidly identify and resolve such problems. METHODS:
      Private provider complaints about RDT buffer vials and kit accessories were
      collected during supervisory visits, and a standard assessment process was
      developed. Using 100 tests drawn from six different lots produced by two
      manufacturers, lab technicians visually assessed alcohol swab packaging, blood
      transfer device (BTD) usability, and buffer appearance, then calculated mean
      blood volume from 10 BTD transfers and mean buffer volume from 10 individual
      buffer vials. WHO guided complaint reporting and follow-up with manufacturers.
      RESULTS: Supervisory visits confirmed user reports of dry alcohol swabs, poorly
      functioning BTDs, and non-uniform volumes of buffer. Lot testing revealed further
      evidence of quality problems, leading one manufacturer to replace buffer vials
      and accessories for 40,000 RDTs. In December 2014, WHO issued an Information
      Notice for Users regarding variable buffer volumes in single-use vials and
      recommended against procurement of these products until defects were addressed.
      DISCUSSION: Though not necessarily comprehensive or generalizable, the findings
      presented here highlight the need for extending quality assessment to all malaria
      RDT test kit contents. Defects such as those described in this paper could reduce
      test accuracy and increase probability of invalid, false positive, or false
      negative results. Such deficiencies could undermine provider confidence in RDTs,
      prompting a return to presumptive treatment or reliance on poor quality
      microscopy. In partial response to this experience, WHO, FIND, and other project
      partners have developed guidance on documenting, troubleshooting, reporting, and
      resolving such problems when they occur.

PMID- 28427429
TI  - Vitamin D receptor, Retinoid X receptor and peroxisome proliferator-activated
      receptor gamma are overexpressed in BRCA1 mutated breast cancer and predict
      prognosis.
AB  - BACKGROUND: BRCA1 mutated breast cancers are commonly diagnosed as negative for
      classical hormone receptors i.e. estrogen receptor, progesterone receptor and/or
      Her2. Due to these common targets being absent the application of anti-endocrine
      therapies is rather limited and a certain focus has been set on discovering
      alternative target molecules. We recently highlighted thyroid hormone receptors
      (TRs) to predict prognosis in breast cancer patients that had been diagnosed a
      BRCA1 germline mutation. Vitamin D Receptor (VDR), Retinoid X Receptor (RXR) and
      Peroxisome Proliferator-activated Receptor gamma (PPARgamma) are known to
      interact with TRs by forming functional heterodimers. Whether VDR, RXR or
      PPARgamma are expressed in BRCA1 mutated breast cancer or may even be present in
      case of triple negativity is not known. Hence the current study aimed to
      investigate VDR, RXR and PPARgamma in BRCA1 mut breast cancer and to test whether
      any of the three may be associated with clinico-pathological criteria including
      overall survival. METHODS: This study analyzed VDR, RXR and PPARgamma by
      immunohistochemistry in BRCA1 associated (n = 38) and sporadic breast cancer (n =
      79). Receptors were quantified by applying an established scoring system (IR
      score) and were tested for association with clinico-pathological variables.
      RESULTS: VDR, RXR and PPARgamma were detected in over 90% of triple negative
      BRCA1 mut breast cancer and were significantly (VDR: p < 0.001, RXR: p = 0.010,
      PPARgamma: p < 0.001) overexpressed in BRCA1 mutated as compared to sporadic
      cancer cases. VDR and RXR positivity predicted prolonged overall survival only in
      BRCA1 mutated cases while such association was not observed in sporadic breast
      cancer. CONCLUSIONS: In conclusion, this is the first study to describe VDR, RXR
      and PPARgamma in BRCA1 mutated breast cancer. Based on the data presented here
      these receptors may be hypothesized to potentially evolve as interesting markers
      or even targets in hereditary breast cancer. However, independent studies are
      indispensable thus to confirm this hypothesis.

PMID- 28427430
TI  - Profile and professional expectations of medical students from 11 Latin American
      countries: the Red-LIRHUS project.
AB  - BACKGROUND: Latin America is undergoing a human resource crisis in health care in
      terms of labor shortage, misdistribution and poor orientation to primary care.
      Workforce data are needed to inform the planning of long-term strategies to
      address this problem. This study aimed to evaluate the academic and motivational
      profile, as well as the professional expectations, of Latin American medical
      students. RESULTS: We conducted an observational, cross-sectional, multi-country
      study evaluating medical students from 11 Spanish-speaking countries in 2011
      2012. Motivations to study medicine, migration intentions, intent to enter
      postgraduate programs, and perceptions regarding primary care were evaluated via
      a self-administered questionnaire. Outcomes were measured with pilot-tested
      questions and previously validated scales. A total of 11,072 valid surveys from
      63 medical schools were gathered and analyzed. CONCLUSIONS: This study describes
      the profile and expectations of the future workforce being trained in Latin
      America. The obtained information will be useful for governments and universities
      in planning strategies to improve their current state of affairs regarding human
      resources for health care professions.

PMID- 28427432
TI  - Anti-human platelet antigen (HPA)-1a antibodies may affect trophoblast functions
      crucial for placental development: a laboratory study using an in vitro model.
AB  - BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding
      disorder caused by maternal antibodies against paternal human platelet antigens
      (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the
      majority of FNAIT cases. We have previously shown that high levels of maternal
      anti-HPA-1a antibodies are associated with clinically significant reduced birth
      weight in newborn boys. Chronic inflammatory placental lesions are associated
      with increased risk of reduced birth weight and have previously been reported in
      connection with FNAIT pregnancies. The HPA-1a epitope is located on integrin
      beta3 that is associated with integrin alphaIIb (the fibrinogen receptor) on
      platelets and megakaryocytes. Integrin beta3 is also associated with integrin
      alphaV forming the alphaVbeta3 integrin heterodimer, the vitronectin receptor,
      which is expressed on various cell types, including trophoblast cells. It is
      therefore thinkable that maternal anti-HPA-1a antibodies present during early
      pregnancy may affect placenta function through binding to the HPA-1a antigen
      epitope on invasive throphoblasts. The aim of the study was to examine whether
      interaction of a human anti-HPA-1a monoclonal antibody (mAb) with HPA-1a on
      trophoblast cells affect adhesion, migration and invasion of extravillous
      trophoblast cells. METHODS: An in vitro model with human anti-HPA-1a mAb, clone
      26.4, and the first trimester extravillous trophoblast cell line HTR8/SVneo was
      employed. The xCELLigence system was utilized to assess the possible effect of
      anti-HPA-1a mAb on adhesion and migration of HTR8/SVneo cells. Specially designed
      chambers precoated with Matrigel were used to assess the effect on the invasive
      capacity of cells. RESULTS: We found that human anti-HPA-1a mAb 26.4 partially
      inhibits adhesion and migratory capacity of HTR8/SVneo cells. CONCLUSIONS: Our
      findings suggest that anti-HPA-1a antibodies may affect trophoblast functions
      crucial for normal placental development. Future studies including primary
      throphoblast cells and polyclonal anti-HPA-1a antibodies are needed to confirm
      these results.

PMID- 28427431
TI  - From inflammation to gastric cancer - the importance of Hedgehog/GLI signaling in
      Helicobacter pylori-induced chronic inflammatory and neoplastic diseases.
AB  - Infections with the human pathogen Helicobacter pylori (H. pylori) are closely
      associated with the development of inflammatory disorders and neoplastic
      transformation of the gastric epithelium. Drastic changes in the micromilieu
      involve a complex network of H. pylori-regulated signal transduction pathways
      leading to the release of proinflammatory cytokines, gut hormones and a wide
      range of signaling molecules. Besides controlling embryonic development, the
      Hedgehog/GLI signaling pathway also plays important roles in epithelial
      proliferation, differentiation, and regeneration of the gastric physiology, but
      also in the induction and progression of inflammation and neoplastic
      transformation in H. pylori infections. Here, we summarize recent findings of H.
      pylori-associated Hedgehog/GLI signaling in gastric homeostasis, malignant
      development and the modulation of the gastric tumor microenvironment.

PMID- 28427433
TI  - Prevalence of subclinical mastitis in Finnish dairy cows: changes during recent
      decades and impact of cow and herd factors.
AB  - BACKGROUND: The dairy industry has undergone substantial structural changes as
      intensive farming has developed during recent decades. Mastitis continues to be
      the most common production disease of dairy cows. Nationwide surveys of mastitis
      prevalence are useful in monitoring udder health of dairy herds and to study the
      impact of structural changes on the dairy industry. This survey on bovine
      subclinical mastitis was the first based on cow composite milk somatic cell count
      (SCC) data from the Finnish national health monitoring and milk recording
      database. A cow with composite milk SCC >=200,000 cells/ml in at least one of the
      four test milkings during the year was considered to have subclinical mastitis
      and a cow with composite milk SCC >=200,000 cells/ml in three or in all four test
      milkings during the year to have chronic subclinical mastitis. The aim of the
      study was to determine the prevalence of subclinical mastitis and chronic
      subclinical mastitis in Finland in 1991, 2001 and 2010 and to investigate cow and
      herd factors associated with elevated SCC. RESULTS: Prevalence of subclinical
      mastitis in Finland decreased over recent decades from 22.3% (1991) and 20.1%
      (2001) to 19.0% (2010). Prevalence of chronic subclinical mastitis was 20.4% in
      1991, 15.5% in 2001 and 16.1% in 2010. The most significant cow and herd factors
      associated with subclinical mastitis or high milk SCC were increasing parity,
      Holstein breed, free-stalls with an automatic milking system and organic
      production. Milk SCC were highest from July to September. Main factors associated
      with chronic mastitis were increasing parity and Holstein breed. CONCLUSIONS:
      Prevalence of subclinical mastitis in Finland decreased over recent decades, the
      greatest change taking place during the first decade of the study. Prevalence of
      chronic subclinical mastitis significantly decreased from 1991. The most
      significant factors associated with both types of mastitis were increasing parity
      and Holstein breed, and for subclinical mastitis also free-stalls with automatic
      milking. National surveys on mastitis prevalence should be carried out at regular
      intervals to monitor udder health of dairy cows and to study the impact of the
      ongoing structural changes in the dairy industry to enable interventions related
      to udder health to be made when needed.

PMID- 28427434
TI  - Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell
      ratio and upregulates death receptors in metastatic melanoma patients.
AB  - BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for
      immunotherapy such as checkpoint blockade antibodies. Still, most patients with
      late stage disease do not respond, and the side effects can be severe.
      Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising
      alternative. Herein, we demonstrate immune profiling data from melanoma patients
      treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS:
      Peripheral blood mononuclear cells and plasma were collected from malignant
      melanoma patients (n = 15) enrolled in a phase I/IIa study investigating
      intratumoral delivery of AdCD40L with or without low dose cyclophosphamide. Cells
      were analyzed by flow cytometry while plasma samples were analyzed by a multi
      array proteomics. RESULTS: All patients had an increased Teffector/Tregulatory
      cell ratio post therapy. Simultaneously, the death receptors TNFR1 and TRAIL-R2
      were significantly up-regulated post treatment. Stem cell factor (SCF), E
      selectin, and CD6 correlated to enhanced overall survival while a high level of
      granulocytic myeloid-derived suppressor cells (gMDSCs), IL8, IL10, TGFb1, CCL4,
      PlGF and Fl3t ligand was highest in patients with short survival. CONCLUSIONS:
      AdCD40L intratumoral injection induced desirable systemic immune effects that
      correlated to prolonged survival. Further studies using CD40 stimulation in
      malignant melanoma are warranted. Trial registration The 002:CD40L trial "Phase
      I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors"
      (clinicalTrials.gov identifier: NCT01455259) was registered at September 2011.

PMID- 28427435
TI  - Prohibitin: targeting peptide coupled to ovarian cancer, luteinization and TGF
      beta pathways.
AB  - BACKGROUND: Ovarian epithelial tumor (OET) is a silent disease of late diagnosis
      and poor prognosis. Currently treatment options are limited and patient response
      to treatment is difficult to predict so there is a serious need to delineate the
      real pathogenesis to predict tumour prognosis. Prohibitin (PHB) is an
      evolutionarily protein that regulates the cell cycle. TGF-beta has been shown to
      be a positive and negative regulator of cellular proliferation and
      differentiation. The present study provides an overview on the role played by
      PHB1, TGF-beta and LH in ovarian cancer. METHODS: The study was conducted on 60
      patients with ovarian tumors (benign, borderline and malignant) and 20 healthy
      volunteers. LH and TGF-beta serum levels were measured by ELISA. Expression of
      prohibitin and LHR-mRNA were assessed by IHC and TaqMan(r) real time gene
      expression assay, respectively. RESULTS: Serum levels of LH and TGF-beta were
      significantly decreased among borderline and malignant groups. There was
      significant over-expression of LHRmRNA in malignant group. Prohibitin expression
      was significantly increased in malignant ovarian tissue. Strong negative
      correlations were found between LHR mRNA expression and serum LH levels, and
      between IHC score of prohibitin and serum levels of LH among patients with
      borderline ovarian tumors. CONCLUSION: Steady decline of LH and TGF-B serum
      levels, from benign cystadenoma to borderline tumor to carcinoma, suggests their
      inhibitory role against OET cell growth. Increased PHB1 expression in OET
      suggests its proliferative activity that can be regulated by luteinisation and/or
      TGF-beta. Furthermore increased LHR mRNA tissue expression can provide hope for
      using LH in treatment of some types of ovarian cancers.

PMID- 28427437
TI  - Efficacy and user acceptability of transfluthrin-treated sisal and hessian
      decorations for protecting against mosquito bites in outdoor bars.
AB  - BACKGROUND: A number of mosquito vectors bite and rest outdoors, which
      contributes to sustained residual malaria transmission in endemic areas. Spatial
      repellents are thought to create a protective "bubble" within which mosquito
      bites are reduced and may be ideal for outdoor use. This study builds on previous
      studies that proved efficacy of transfluthrin-treated hessian strips against
      outdoor biting mosquitoes. The goal of this study was to modify strips into
      practical, attractive and acceptable transfluthrin treated sisal and hessian
      emanators that confer protection against potential infectious bites before people
      use bed nets especially in the early evening and outdoors. This study was
      conducted in Kilombero Valley, Ulanga District, south-eastern Tanzania. RESULTS:
      The protective efficacy of hand-crafted transfluthrin-treated sisal decorative
      baskets and hessian wall decorations against early evening outdoor biting malaria
      vectors was measured by human landing catches (HLC) in outdoor bars during peak
      outdoor mosquito biting activity (19:00 to 23:00 h). Treated baskets and wall
      decorations reduced bites of Anopheles arabiensis mosquitoes by 89% (Relative
      Rate, RR = 0.11, 95% confidence interval, CI: 0.09-0.15, P < 0.001) and 86% (RR =
      0.14, 95% CI: 0.11-0.18, P < 0.001), respectively. In addition, they
      significantly reduced exposure to outdoor bites of Culex spp. by 66% (RR = 0.34,
      95% CI: 0.22-0.52, P < 0.001) and 56% (RR = 0.44, 95% CI: 0.29-0.66, P < 0.001),
      respectively. CONCLUSION: Locally hand-crafted transfluthrin-treated sisal
      decorative baskets and hessian wall decorations are readily acceptable and confer
      protection against outdoor biting malaria vectors in the early evening and
      outdoors: when people are resting on the verandas, porches or in outdoor social
      places such as bars and restaurants. Additional research can help support the use
      of such items as complementary interventions to expand protection to communities
      currently experiencing outdoor transmission of mosquito-borne pathogens.

PMID- 28427436
TI  - A 3D in vitro model of the human breast duct: a method to unravel myoepithelial
      luminal interactions in the progression of breast cancer.
AB  - BACKGROUND: 3D modelling fulfils a critical role in research, allowing for
      complex cell behaviour and interactions to be studied in physiomimetic
      conditions. With tissue banks becoming established for a number of cancers,
      researchers now have access to primary patient cells, providing the perfect
      building blocks to recreate and interrogate intricate cellular systems in the
      laboratory. The ducts of the human breast are composed of an inner layer of
      luminal cells supported by an outer layer of myoepithelial cells. In early-stage
      ductal carcinoma in situ, cancerous luminal cells are confined to the ductal
      space by an intact myoepithelial layer. Understanding the relationship between
      myoepithelial and luminal cells in the development of cancer is critical for the
      development of new therapies and prognostic markers. This requires the generation
      of new models that allows for the manipulation of these two cell types in a
      physiological setting. METHODS: Using access to the Breast Cancer Now Tissue
      Bank, we isolated pure populations of myoepithelial and luminal cells from human
      reduction mammoplasty specimens and placed them into 2D culture. These cells were
      infected with lentiviral particles encoding either fluorescent proteins, to
      facilitate cell tracking, or an inducible human epidermal growth factor receptor
      2 (HER2) expression construct. Myoepithelial and luminal cells were then
      recombined in collagen gels, and the resulting cellular structures were analysed
      by confocal microscopy. RESULT S: Myoepithelial and luminal cells isolated from
      reduction mammoplasty specimens can be grown separately in 2D culture and retain
      their differentiated state. When recombined in collagen gels, these cells reform
      into physiologically reflective bilayer structures. Inducible expression of HER2
      in the luminal compartment, once the bilayer has formed, leads to robust luminal
      filling, recapitulating ductal carcinoma in situ, and can be blocked with anti
      HER2 therapies. CONCLUSIONS: This model allows for the interaction between
      myoepithelial and luminal cells to be investigated in an in-vitro environment and
      paves the way to study early events in breast cancer development with the
      potential to act as a powerful drug discovery platform.

PMID- 28427438
TI  - Canine beta-defensin-1 (CBD1) gene as a possible marker for Leishmania infantum
      infection in dogs.
AB  - BACKGROUND: Canine leishmaniasis caused by Leishmania infantum is a parasitic
      disease of great veterinary significance. Some dogs infected by L. infantum may
      mount a strong cellular immune response and clear the infection, while others may
      respond with exaggerated antibody production against the parasite and develop an
      overt disease, which may be fatal, if left untreated. The initial factors
      triggering the polarization of the immune response towards a predominantly T
      helper 1 or T-helper 2 cytokines, as well as the markers of resistance and
      susceptibility to L. infantum infection and disease development in dogs, are not
      fully understood. Herein, we assessed the association between single nucleotide
      polymorphisms (SNPs) in the canine beta-defensin-1 (CBD1) gene and the infection
      by L. infantum in two dog populations from Brazil (Sobral in Ceara State and Sao
      Raimundo Nonato in Piaui State) and one dog population from Italy. RESULTS: A
      total of 387 dogs were assessed for L. infantum by real time PCR and 34.6% of
      them were positive. In CBD1 gene sequences from these positive dogs, nine
      polymorphic sites were detected, but only SNPs 3, 4, 7 and 8 were associated with
      L. infantum, in dogs from southern Italy. No association was found with dogs from
      Brazil. CONCLUSION: This study sets the basis for further studies on the
      usefulness of CBD1 as a marker of L. infantum infection susceptibility in dogs.

PMID- 28427439
TI  - Prevalence and prognostic implications of psychological distress in patients with
      gastric cancer.
AB  - BACKGROUND: The aim of this study was to investigate the prevalence and
      prognostic significance of psychological distress in gastric cancer patients.
      METHODS: The study population included 229 gastric cancer patients visiting
      Yonsei Cancer Center between November 2009 and March 2011. The distress was
      measured by available tools including the Modified Distress Thermometer (MDT),
      Hospital Anxiety and Depression Scale (HADS), and Center for Epidemiologic
      Studies-Depression Scale (CES-D). Patients with psychological distress were
      defined as those who scored above the cut-off values in both the MDT and either
      one of the HADS or CES-D. RESULTS: The median age of patients was 56 (range, 20
      to 86) and 97 (42.4%) patients were with stage IV disease status at enrollment.
      The overall prevalence of psychological distress was 33.6% (95% CI: 27.5-39.8%)
      in 229 gastric cancer patients. In multiple logistic regression analysis, lower
      education level (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.11-5.17, P
      = 0.026) and higher disease stage (OR 2.72; 95% CI 1.47-5.03, P = 0.001) were
      associated with psychological distress. In stage I-III disease, patients with
      psychological distress had worse disease-free survival (DFS) (5-year DFS rate:
      60% vs 76%, P = 0.49) compared with those without psychological distress. In
      stage IV disease (n = 97), patients with psychological distress showed poorer
      overall survival than those without psychological distress (median OS (Overall
      Survival): 12.2 vs. 13.8 months, P = 0.019). CONCLUSION: Psychological distress
      is common in patients with all stages of gastric cancer and is associated with
      worse outcomes.

PMID- 28427440
TI  - Hypoglycemia identified by a continuous glucose monitoring system in a second
      trimester pregnant woman with insulinoma: a case report.
AB  - BACKGROUND: Insulinoma associated with pregnancy is a very rare condition and can
      be difficult to diagnose. Here, we present an interesting case of insulinoma
      occurring during pregnancy with special attention paid to the use of a continuous
      glucose monitoring system to detect hypoglycemia. CASE PRESENTATION: A 36-year
      old white woman in the second trimester of pregnancy presented with recurrent
      episodes of hypoglycemia associated with neuroglycopenic symptoms. The use of a
      continuous glucose monitoring system confirmed hypoglycemia. Serum insulin, C
      peptide, and proinsulin values confirmed endogenous hyperinsulinism. A tumor mass
      was localized at the tail of her pancreas by endoscopic ultrasound and confirmed
      by magnetic resonance imaging. Surgery performed at 21 weeks of gestation by
      distal pancreatectomy confirmed the presence of a 15 mm diameter endocrine tumor
      at the tail of her pancreas and led to a cure. CONCLUSIONS: Hypoglycemia during
      pregnancy could be due to insulinoma. Use of a continuous glucose monitoring
      system could help to detect hypoglycemia in these patients.

PMID- 28427441
TI  - Physical activity among children: objective measurements using Fitbit One(r) and
      ActiGraph.
AB  - BACKGROUND: Self-quantification of health parameters is becoming more popular;
      thus, the validity of the devices requires assessments. The aim of this study was
      to evaluate the validity of Fitbit One step counts (Fitbit Inc., San Francisco,
      CA, USA) against Actigraph wActisleep-BT step counts (ActiGraph, LLC, Pensacola,
      FL, USA) for measuring habitual physical activity among children. DESIGN: The
      study was implemented as a cross-sectional experimental design in which
      participants carried two waist-worn activity monitors for five consecutive days.
      METHODS: The participants were chosen with a purposive sampling from three fourth
      grade classes (9-10 year olds) in two comprehensive schools. Altogether, there
      were 34 participants in the study. From these, eight participants were excluded
      from the analysis due to erroneous data. Primary outcome measures for step counts
      were Fitbit One and Actigraph wActisleep-BT. The supporting outcome measures were
      based on activity diaries and initial information sheets. Classical Bland-Altman
      plots were used for reporting the results. RESULTS: The average per-participant
      daily difference between the step counts from the two devices was 1937. The range
      was [116, 5052]. Fitbit One gave higher step counts for all but the least active
      participant. According to a Bland-Altman plot, the hourly step counts had a
      relative large mean bias across participants (161 step counts). The differences
      were partially explained by activity intensity: higher intensity denoted higher
      differences, and light intensity denoted lower differences. CONCLUSIONS: Fitbit
      One step counts are comparable to Actigraph step counts in a sample of 9-10-year
      old children engaged in habitual physical activity in sedentary and light
      physical activity intensities. However, in moderate-to-vigorous physical
      activity, Fitbit One gives higher step counts when compared to Actigraph.

PMID- 28427442
TI  - Effect of acupuncture in prevention and treatment of chemotherapy-induced nausea
      and vomiting in patients with advanced cancer: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is one of the most
      common and distressing side effects in patients with cancer. The introduction and
      development of antiemetic drugs have significantly improved the ability of
      clinicians to control CINV, but it is not easy to translate to practical
      application, owing to financial issues, provider-related barriers, and patient
      factors. Nondrug therapies are needed to alleviate the symptoms of CINV.
      Acupuncture is an appropriate adjunctive treatment for CINV, but additional
      evidence is needed. METHODS/DESIGN: This study is a multicenter, randomized, sham
      controlled prospective clinical trial. A total of 136 participants will be
      randomly allocated into the intervention group (verum acupuncture) or the control
      group (sham acupuncture) in a 1:1 ratio. All treatment will be given for 5 days.
      Participants in both groups will receive acupuncture sessions twice on the first
      day of chemotherapy and once consecutively on the following 4 days. Each session
      takes approximately 30 minutes. The primary outcome measure will be the Common
      Terminology Criteria for Adverse Events to assess CINV. The secondary outcome
      measures will be the Eastern Cooperative Oncology Group score, Simplified
      Nutritional Appetite Questionnaire, and Hospital Anxiety and Depression scale.
      Safety will be assessed at each visit. DISCUSSION: The results of this trial will
      provide clinical evidence for the effect and safety of acupuncture for CINV.
      TRIAL REGISTRATIONS: ISRCTN Registry identifier: ISRCTN13287728 ). Registered on
      28 February 2015. ClinicalTrials.gov identifier: NCT02369107 . Registered on 17
      February 2015.

PMID- 28427443
TI  - Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting
      hexokinase 2.
AB  - BACKGROUND: Hexokinase (HK) is the rate-limiting enzyme in the first reaction of
      glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor
      which expresses at higher level compared with normal cells. HK2 plays a pivotal
      role in tumor initiation and maintenance, which provides a new target for cancer
      therapy. METHODS: Structure-based virtual ligand screening was used in hit
      identification from ZINC Drug Database. Microscale thermophoresis assay was
      performed to evaluate the binding affinity. Enzyme inhibition, cytotoxicity,
      apoptosis, intracellular ATP level, mitochondrial membrane potential (MMP),
      glucose uptake and lactate production experiments were undertaken in SW480 cells
      to identify Benz as a HK2 inhibitor. Western blot was used to test protein
      expression. SW480 cells xenograft mouse models were used for in vivo study. Nano
      particles of Benz were prepared to improve the antitumor efficacy and tumor
      targeting of Benz. HPLC was used to measure the concentration of free Benz in
      tumor tissues. RESULTS: Benserazide (Benz), was identified as a selective HK2
      inhibitor, could specifically bind to HK2 and significantly inhibit HK2 enzymatic
      activity in vitro. In addition, Benz reduced glucose uptake, lactate production
      and intracellular ATP level, and could cause cell apoptosis and an increased loss
      of MMP as well. In vivo study indicated that intraperitoneal (ip) injection of
      Benz at 300 and 600 mg/Kg suppressed cancer growth in tumor-bearing mice and no
      toxicity shown. To further improve the antitumor efficacy and tumor targeting of
      Benz, nano-particles of Benz was prepared. Liposomal Benz at 100 and 200 mg/Kg
      performed potent inhibitory effects on tumor-bearing mice, showing reduced dose
      and better efficacy. CONCLUSIONS: Our study provides a new direction for the
      development of Benz and its analogues as novel antitumor agents for cancer
      therapy.

PMID- 28427444
TI  - Interventions to reduce wait times for primary care appointments: a systematic
      review.
AB  - BACKGROUND: Accessibility and availability are important characteristics of
      efficient and effective primary healthcare systems. Currently, timely access to a
      family physician is a concern in Canada. Adverse outcomes are associated with
      longer wait times for primary care appointments and often leave individuals to
      rely on urgent care. When wait times for appointments are too long patients may
      experience worse health outcomes and are often left to use emergency department
      resources. The primary objective of our study was to systematically review the
      literature to identify interventions designed to reduce wait times for primary
      care appointments. Secondary objectives were to assess patient satisfaction and
      reduction of no-show rates. METHODS: We searched multiple databases, including:
      Medline via Ovid SP (1947 to present), Embase (from 1980 to present), PsychINFO
      (from 1806 to present), Cochrane Central Register of Controlled Trials (CENTRAL;
      all dates), Cumulative Index to Nursing and Allied Health (CINAHL; 1937 to
      present), and Pubmed (all dates) to identify studies that reported outcomes
      associated with interventions designed to reduce wait times for primary care
      appointments. Two independent reviewers assessed all identified studies for
      inclusion using pre-defined inclusion/exclusion criteria and a multi-level
      screening approach. Our study methods were guided by the Cochrane Handbook for
      Systematic Reviews of Interventions. RESULTS: Our search identified 3,960
      articles that were eligible for inclusion, eleven of which satisfied all
      inclusion/exclusion criteria. Data abstraction of included studies revealed that
      open access scheduling is the most commonly used intervention to reduce wait
      times for primary care appointments. Additionally, included studies demonstrated
      that dedicated telephone calls for follow-up consultation, presence of nurse
      practitioners on staff, nurse and general practitioner triage, and email
      consultations were effective at reducing wait times. CONCLUSIONS: To our
      knowledge, this is the first study to systematically review and identify
      interventions designed to reduce wait times for primary care appointments. Our
      findings suggest that open access scheduling and other patient-centred
      interventions may reduce wait times for primary care appointments. Our review may
      inform policy makers and family healthcare providers about interventions that are
      effective in offering timely access to primary healthcare.

PMID- 28427445
TI  - Parasites, pathogens and commensals in the "low-impact" non-native amphipod host
      Gammarus roeselii.
AB  - BACKGROUND: Whilst vastly understudied, pathogens of non-native species (NNS) are
      increasingly recognised as important threats to native wildlife. This study
      builds upon recent recommendations for improved screening for pathogens in NNS by
      focusing on populations of Gammarus roeselii in Chojna, north-western Poland. At
      this location, and in other parts of continental Europe, G. roeselii is
      considered a well-established and relatively 'low-impact' invader, with little
      understanding about its underlying pathogen profile and even less on potential
      spill-over of these pathogens to native species. RESULTS: Using a combination of
      histological, ultrastructural and phylogenetic approaches, we define a pathogen
      profile for non-native populations of G. roeselii in Poland. This profile
      comprised acanthocephalans (Polymorphus minutus Goese, 1782 and Pomphorhynchus
      sp.), digenean trematodes, commensal rotifers, commensal and parasitic ciliated
      protists, gregarines, microsporidia, a putative rickettsia-like organism,
      filamentous bacteria and two viral pathogens, the majority of which are
      previously unknown to science. To demonstrate potential for such pathogenic risks
      to be characterised from a taxonomic perspective, one of the pathogens, a novel
      microsporidian, is described based upon its pathology, developmental cycle and
      SSU rRNA gene phylogeny. The novel microsporidian Cucumispora roeselii n. sp.
      displayed closest morphological and phylogenetic similarity to two previously
      described taxa, Cucumispora dikerogammari (Ovcharenko & Kurandina, 1987), and
      Cucumispora ornata Bojko, Dunn, Stebbing, Ross, Kerr & Stentiford, 2015.
      CONCLUSIONS: In addition to our discovery extending the host range for the genus
      Cucumispora Ovcharenko, Bacela, Wilkinson, Ironside, Rigaud & Wattier, 2010
      outside of the amphipod host genus Dikerogammarus Stebbing, we reveal significant
      potential for the co-transfer of (previously unknown) pathogens alongside this
      host when invading novel locations. This study highlights the importance of pre
      invasion screening of low-impact NNS and, provides a means to document and
      potentially mitigate the additional risks posed by previously unknown pathogens.

PMID- 28427447
TI  - Benchmarking insecticide resistance intensity bioassays for Anopheles malaria
      vector species against resistance phenotypes of known epidemiological
      significance.
AB  - BACKGROUND: Insecticide use via indoor residual spraying (IRS) or treated nets is
      the primary method for controlling malaria vector populations. The incidence of
      insecticide resistance in vector populations is burgeoning globally making
      resistance management key to the design of effective malaria control and
      elimination strategies. Vector populations can be assessed for insecticide
      resistance using a binary (susceptible or resistant) classification based on the
      use of the standard WHO insecticide susceptibility assay for adult anopheline
      mosquitoes. However, the recent scaling up of vector control activities has
      necessitated a revision of the WHO bioassay protocol to include the production of
      information that not only diagnoses resistance but also gives information on the
      intensity of expression of resistance phenotypes detected. This revised protocol
      is expected to inform on the range of resistance phenotypes in a target vector
      population using discriminating/diagnostic insecticide concentrations (DC) as
      well as their potential operational significance using 5* DC and 10* DC assays.
      The aim of this project was to use the revised protocol to assess the intensity
      of pyrethroid resistance in a range of insecticide resistant Anopheles strains
      with known resistance mechanisms and for which there is evidence of operational
      significance in the field setting from which these colonies were derived.
      METHODS: Diagnostic concentration (DC) bioassays followed by 5* DC and 10* DC
      assays using the pyrethroid insecticides permethrin and deltamethrin were
      conducted according to the standard WHO bioassay method against pyrethroid
      resistant laboratory strains of Anopheles funestus, An. arabiensis and An.
      gambiae. RESULTS: Low to moderate resistance intensities were recorded for the
      An. arabiensis and An. gambiae strains while moderate to high intensities were
      recorded for the An. funestus strains. CONCLUSIONS: It is evident that resistance
      intensity assays can add predictive value to the decision making process in
      vector control settings, although more so in an IRS setting and especially when
      bench-marked against resistance phenotypes of known operational significance.

PMID- 28427446
TI  - Respiratory chain complex III deficiency due to mutated BCS1L: a novel phenotype
      with encephalomyopathy, partially phenocopied in a Bcs1l mutant mouse model.
AB  - BACKGROUND: Mitochondrial diseases due to defective respiratory chain complex III
      (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is
      completed by the insertion of the Rieske iron-sulfur protein, a process for which
      BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most
      common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising
      from mutations in this gene is wide. RESULTS: A case of CIII deficiency was
      investigated in depth to assess respiratory chain function and assembly, and
      brain, skeletal muscle and liver histology. Exome sequencing was performed to
      search for the causative mutation(s). The patient's platelets and muscle
      mitochondria showed respiration defects and defective assembly of CIII was
      detected in fibroblast mitochondria. The patient was compound heterozygous for
      two novel mutations in BCS1L, c.306A > T and c.399delA. In the cerebral cortex a
      specific pattern of astrogliosis and widespread loss of microglia was observed.
      Further analysis showed loss of Kupffer cells in the liver. These changes were
      not found in infants suffering from GRACILE syndrome, the most severe BCS1L
      related disorder causing early postnatal mortality, but were partially
      corroborated in a knock-in mouse model of BCS1L deficiency. CONCLUSIONS: We
      describe two novel compound heterozygous mutations in BCS1L causing CIII
      deficiency. The pathogenicity of one of the mutations was unexpected and points
      to the importance of combining next generation sequencing with a biochemical
      approach when investigating these patients. We further show novel manifestations
      in brain, skeletal muscle and liver, including abnormality in specialized
      resident macrophages (microglia and Kupffer cells). These novel phenotypes
      forward our understanding of CIII deficiencies caused by BCS1L mutations.

PMID- 28427448
TI  - Capture-recapture methodology to study rare conditions using surveillance data
      for fragile X syndrome and muscular dystrophy.
AB  - BACKGROUND: Rare conditions can be catastrophic for families and the implications
      for public health can be substantial. Our study compared basic surveillance
      through active medical record review with a linked administrative data file to
      assess the number of cases of two rare conditions, fragile X syndrome (FXS) and
      muscular dystrophy (MD) in a population. METHODS: Two methods of data collection
      were used to collect information from five counties comprising two standard
      metropolitan statistical areas of South Carolina. The passive system relied
      mostly on health claims data using ICD-9 CM diagnostic codes. The active system
      relied on a nurse abstracting records from a list of all licensed physicians with
      specialties in neurology, orthopedics, and genetics. RESULTS: There were 141 FXS
      cases and 348 MD cases that met the case definitions using active surveillance.
      Additional cases were found for both conditions but they were determined to not
      be true cases. After linking the actively collected MD and FXS cases to passive
      datasets, we found that the estimated total numbers of cases were similar to
      using capture-recapture analysis; the positive predictive values for cases
      identified in the passive system were 56.6% for MD and 75.7% for FXS.
      CONCLUSIONS: Applying capture-recapture methods to passively collected
      surveillance data for rare health conditions produced an estimate of the number
      of true cases that was similar to that obtained through active data collection.

PMID- 28427449
TI  - Urolithiasis analysis in a multiethnic population at a tertiary hospital in
      Nairobi, Kenya.
AB  - BACKGROUND: Urolithiasis is a global problem whose incidence is reported to be on
      the rise across the world. Previously, urolithiasis was reported as being rare
      among the indigenous African population but recent data suggest otherwise. This
      study reviewed the demographic and clinical characteristics of patients with
      urolithiasis seen at the Aga Khan University hospital Nairobi (AKUHN) as well as
      the chemical composition of the stones and the modalities of therapy used.
      METHODS: This was a retrospective study which utilized patients' clinical and
      laboratory records from 2013 to 2014. Sixty-seven symptomatic patients with
      confirmed urolithiasis formed the study. This study aimed to describe the
      clinical characteristics of patients, modalities of treatment as well as the
      chemical composition of renal stones from patients diagnosed and managed for
      urolithiasis during a duration spanning 17 months. Wet chemistry was utilized for
      analyzing the chemical composition of the urinary calculi. Data on age, sex,
      symptoms, radiological investigations done, location of the calculi, chemical
      composition of calculi and therapeutic procedures instituted were extracted and
      analyzed. RESULTS: Ages ranged from 3 to 87 years with a median of 42; males were
      the majority (79%) and the commonest presenting symptoms were flank pain (91%)
      and dysuria (19%). The majority of the stones were located in the ureters (46%)
      and at the pelvi-ureteric junction (25%). A statistically significant difference
      in frequency of lodgment at the pelvi-ureteric site between males and females was
      noted. However, the number of female patients in this study was small and studies
      with larger numbers of female participants are required to confirm this
      observation. All stones contained calcium and oxalate, often as the only
      constituents (72%). In the remainder of the stones, other constituents such
      bicarbonate, ammonium, phosphorous, magnesium, uric acid and cystine occurred in
      varying combinations with calcium oxalate. Laser lithotripsy was the most
      performed therapeutic procedure (77.6%). CONCLUSIONS: Males formed the majority
      of patient with urolithiasis. Overall, most of the calculi were located in the
      ureters except in women where the pelviureteric location was commoner. Stones
      containing calcium oxalate only were predominant across the age groups and in
      both sexes. Lithotripsy was the commonest mode of management.

PMID- 28427450
TI  - Presence of susceptible wild strains of Anopheles gambiae in a large industrial
      palm farm located in Aboisso, South-Eastern of Cote d'Ivoire.
AB  - BACKGROUND: The effectiveness of malaria control programmes through
      implementation of vector control activities is challenged by the emergence of
      insecticide resistance. In the South-Eastern region of Cote d'Ivoire, where palm
      oil plantations remain the predominant agricultural crop, the susceptibility of
      wild Anopheles gambiae sensu lato species is still unknown and thus requires a
      particular attention. The current study was carried out to address the gap by in
      depth characterization of susceptibility level of An. gambiae mosquitoes from
      Ehania-V1 to WHO-recommended doses of six insecticides belonging to available
      classes and also to screen a subset for target site mutations and possible
      inhibition of P450 enzymes. RESULTS: Overall results showed variable resistance
      profile across WHO-recommended insecticides tested. Mortalities ranged from 8.3%
      (the lowest mortality was recorded with DDT) to 98% (the highest mortality was
      recorded with fenitrothion). Importantly, mortality to deltamethrin, an important
      pyrethroid used in public health for impregnation of mosquito nets was close to
      98%, precluding a possible susceptibility to this insecticide, albeit further
      investigations are required. Pre-exposure of An. gambiae s.l. to PBO did not show
      any significant variation across insecticides (p = 0.002), although a partial
      increase was detected for alphacypermethrin and bendiocarb, suggesting a low of
      activity of cytochrome P450 enzymes (p = 0.277). High frequency of kdr L1014F was
      recorded in both Anopheles coluzzii (91%) and in An. gambiae (96%), associated
      with ace-1 R G119S mutation at low frequency (<20%). CONCLUSION: The high
      mortality rate to deltamethrin, organophosphate and the non-detection of P450
      activity in resistance observed in Ehania-V1 appears as a positive outcome for
      further control strategies as metabolic-based P450 resistance remains major
      challenge to manage. These results should help the National Malaria Control
      Programme when designing strategies for vector control in palm oil areas of Cote
      d'Ivoire.

PMID- 28427451
TI  - Household level spatio-temporal analysis of Plasmodium falciparum and Plasmodium
      vivax malaria in Ethiopia.
AB  - BACKGROUND: The global decline of malaria burden and goals for elimination has
      led to an increased interest in the fine-scale epidemiology of malaria. Micro
      geographic heterogeneity of malaria infection could have implications for
      designing targeted small-area interventions. METHODS: Two-year longitudinal
      cohort study data were used to explore the spatial and spatio-temporal
      distribution of malaria episodes in 2040 children aged < 10 years in 16 villages
      near the Gilgel-Gibe hydropower dam in Southwest Ethiopia. All selected
      households (HHs) were geo-referenced, and children were followed up through
      weekly house-to-house visits for two consecutive years to identify febrile
      episodes of P. falciparum and P. vivax infections. After confirming the spatial
      dependence of malaria episodes with Ripley's K function, SatScanTM was used to
      identify purely spatial and space-time clusters (hotspots) of annual malaria
      incidence for 2 years follow-up: year 1 (July 2008-June 2009) and year 2 (July
      2009-June 2010). RESULTS: In total, 685 P. falciparum episodes (in 492 HHs) and
      385 P. vivax episodes (in 290 HHs) were identified, representing respectively
      incidence rates of 14.6 (95% CI: 13.4-15.6) and 8.2 (95% CI: 7.3-9.1) per 1000
      child-months at risk. In year 1, the most likely (128 HHs with 63 episodes, RR =
      2.1) and secondary (15 HHs with 12 episodes, RR = 5.31) clusters of P. vivax
      incidence were found respectively in southern and north-western villages; while
      in year 2, the most likely cluster was located only in north-western villages (85
      HHs with 16 episodes, RR = 4.4). Instead, most likely spatial clusters of P.
      falciparum incidence were consistently located in villages south of the dam in
      both years: year 1 (167 HHs with 81 episodes, RR = 1.8) and year 2 (133 HHs with
      67 episodes, RR = 2.2). Space-time clusters in southern villages for P. vivax
      were found in August-November 2008 in year 1 and between November 2009 and
      February 2010 in year 2; while for P. falciparum, they were found in September
      November 2008 in year 1 and October-November 2009 in year 2. CONCLUSION: Hotspots
      of P. falciparum incidence in children were more stable at the geographical level
      and over time compared to those of P. vivax incidence during the study period.

PMID- 28427452
TI  - Modeling environmental risk factors of autism in mice induces IBD-related gut
      microbial dysbiosis and hyperserotonemia.
AB  - Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that
      are sharply increasing in prevalence worldwide. Intriguingly, ASD is often
      accompanied by an array of systemic aberrations including (1) increased
      serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory
      bowel disease (IBD), albeit the underlying cause for such comorbidities remains
      uncertain. Also, accumulating number of studies report that the gut microbial
      composition is significantly altered in children with ASD or patients with IBD.
      Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced
      mouse models of ASD, we found a distinct pattern of microbial dysbiosis that
      highly recapitulated those reported in clinical cases of ASD and IBD. Moreover,
      we report that such microbial dysbiosis led to notable perturbations in microbial
      metabolic pathways that are known to negatively affect the host, especially with
      regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of
      serotonin is significantly increased in both poly I:C and VPA mice, and that it
      correlates with increases of a bacterial genus and a metabolic pathway that are
      implicated in stimulation of host serotonin production. Our results using animal
      model identify prenatal environmental risk factors of autism as possible
      causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a
      multifaceted role of gut microbiota in the systemic pathogenesis of ASD and
      hyperserotonemia.

PMID- 28427453
TI  - The Italian Society for Pediatric Nephrology (SINePe) consensus document on the
      management of nephrotic syndrome in children: Part I - Diagnosis and treatment of
      the first episode and the first relapse.
AB  - This consensus document is aimed at providing an updated, multidisciplinary
      overview on the diagnosis and treatment of pediatric nephrotic syndrome (NS) at
      first presentation. It is the first consensus document of its kind to be produced
      by all the pediatric nephrology centres in Italy, in line with what is already
      present in other countries such as France, Germany and the USA. It is based on
      the current knowledge surrounding the symptomatic and steroid treatment of NS,
      with a view to providing the basis for a separate consensus document on the
      treatment of relapses. NS is one of the most common pediatric glomerular
      diseases, with an incidence of around 2-7 cases per 100000 children per year.
      Corticosteroids are the mainstay of treatment, but the optimal therapeutic
      regimen for managing childhood idiopathic NS is still under debate. In Italy,
      shared treatment guidelines were lacking and, consequently, the choice of steroid
      regimen was based on the clinical expertise of each individual unit. On the basis
      of the 2015 Cochrane systematic review, KDIGO Guidelines and more recent data
      from the literature, this working group, with the contribution of all the
      pediatric nephrology centres in Italy and on the behalf of the Italian Society of
      Pediatric Nephrology, has produced a shared steroid protocol that will be useful
      for National Health System hospitals and pediatricians. Investigations at initial
      presentation and the principal causes of NS to be screened are suggested. In the
      early phase of the disease, symptomatic treatment is also important as many
      severe complications can occur which are either directly related to the
      pathophysiology of the underlying NS or to the steroid treatment itself. To date,
      very few studies have been published on the prophylaxis and treatment of these
      early complications, while recommendations are either lacking or conflicting.
      This consensus provides indications for the prevention, early recognition and
      treatment of these complications (management of edema and hypovolemia, therapy
      and prophylaxis of infections and thromboembolic events). Finally,
      recommendations about the clinical definition of steroid resistance and its
      initial diagnostic management, as well as indications for renal biopsy are
      provided.

PMID- 28427455
TI  - Comparison of methods for detecting asymptomatic malaria infections in the China
      Myanmar border area.
AB  - BACKGROUND: Sensitive methods for detecting asymptomatic malaria infections are
      essential for identifying potential transmission reservoirs and obtaining an
      accurate assessment of malaria epidemiology in low-endemicity areas aiming to
      eliminate malaria. PCR techniques to detect parasite nucleic acids (DNA or RNA)
      are among the most commonly used molecular methods. However, most of these
      methods are of low throughput and cannot be used for large-scale molecular
      epidemiological studies. A recently developed capture and ligation probe-PCR
      (CLIP-PCR) is claimed to have the sensitivity of molecular techniques and the
      high throughput capacity needed for screening purposes. This study aimed to
      compare several molecular methods for detecting asymptomatic and submicroscopic
      Plasmodium infections in healthy residents of a malaria-hypoendemic region in
      Southeast Asia, where malaria elimination is in sight. METHOD: This study
      compared three molecular detection methods side-by-side, namely nested PCR
      targeting the rRNA genes, nested RT-PCR to detect parasite rRNA, and CLIP-PCR to
      detect parasite rRNA in 1005 healthy individuals in northeastern Myanmar. For
      nested PCR and RT-PCR, parasite DNA and total RNA were extracted from ~100 uL of
      blood, whereas RNA used for CLIP-PCR was from a 3 mm disk of dried blood filter
      paper. The sensitivity and specificity of these methods were compared with those
      of conventional light microscopy. In addition, RT-PCR and quantitative RT-PCR
      (qRT-PCR) targeting the Pvs25 gene in Plasmodium vivax were used to assess
      gametocyte prevalence in the samples. RESULTS: Light microscopy detected
      Plasmodium infections in only 1.19% of the residents harbouring the parasites.
      CLIP-PCR had slightly better performance and detected Plasmodium infections in
      1.89% of the population. Further improvement was achieved by nested PCR to detect
      parasite DNA, which detected P. vivax and Plasmodium falciparum infections in
      2.39% of the residents. The nested RT-PCR targeting rRNA, however, detected as
      many as 187 (18.61%) individuals having Plasmodium infections with P. vivax being
      the predominant species (176 P. vivax, 5 P. falciparum and 6 P. falciparum/P.
      vivax mixed infections). Of the 210 Plasmodium-positive samples detected by all
      molecular methods, 115 were Pvs25-positive by qRT-PCR, indicating that a large
      proportion of asymptomatic individuals were gametocyte carriers. CONCLUSION:
      Nested RT-PCR based on the detection of asexual-stage parasite rRNA was the most
      sensitive, with a more than sixfold higher sensitivity than the other two
      molecular methods of parasite detection. CLIP-PCR has an increased throughput,
      but its sensitivity in this study was much lower than those of other molecular
      methods, which may be partially due to the smaller amount of RNA input used.

PMID- 28427456
TI  - A multicenter randomized controlled trial of surgery alone or surgery with atrial
      natriuretic peptide in lung cancer surgery: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Postoperative cancer recurrence is a major problem following curative
      surgery. In a previous retrospective study of lung cancer surgery, we reported
      that administration of atrial natriuretic peptide (ANP) during the perioperative
      period reduced postoperative recurrence. We demonstrated that ANP inhibited the
      adhesion of cancer cells to vascular endothelium as a vasoprotective action. The
      objective of this study is to evaluate the effects of ANP on the incidence of
      postoperative cancer recurrence in lung cancer surgery. METHODS/DESIGN: The
      present study is a multicenter, randomized trial with two parallel groups of
      patients with lung cancer comparing surgery alone and surgery with ANP
      administration for 3 days during the perioperative period. A total of 500
      patients will be enrolled from 10 Japanese institutions. The primary endpoint is
      2-year relapse-free survival (RFS). The secondary endpoints are 2-year cancer
      specific RFS, 5-year RFS, overall survival, the incidence of postoperative
      complications, and the completion rate of ANP treatment. DISCUSSION: The
      principal question addressed in this trial is whether ANP with its vasoprotective
      action can reduce cancer recurrence following lung cancer surgery. TRIAL
      REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000018480 .
      Registered on 31 July 2015.

PMID- 28427457
TI  - Integrative modelling of TIR domain-containing adaptor molecule inducing
      interferon-beta (TRIF) provides insights into its autoinhibited state.
AB  - BACKGROUND: TRIF is a key protein in antiviral innate immunity, operating
      downstream of TLRs. TRIF activation leads to the production of interferon-beta
      and pro-inflammatory cytokines. There is evidence from experiments to suggest
      that the N-terminal domain of TRIF binds to its TIR domain to avoid constitutive
      activation. However, no structure of a complex between the N-terminal domain and
      the TIR domain exists till date. The disordered nature of the region connecting
      the N-terminal domain and the TIR domain compounds the issue of elucidating the
      mechanism of autoinhibition of TRIF. In this study, we have employed an
      integrative approach consisting of mutual information analysis, docking,
      molecular dynamics simulations and residue network analysis, in combination with
      existing experimental data to provide a glimpse of TRIF in its autoinhibited
      state. RESULTS: Our extensive docking approach reveals that the N-terminal domain
      binds to the BB loop-B helix region of the TIR domain, consistent with
      experimental observations. Long length molecular dynamics simulations of 1
      microsecond performed on the docked model highlights residues participating in
      hydrogen bonding and hydrophobic interactions at the interface. A pair of
      residues present in the vicinity of the interface is also predicted by mutual
      information analysis, to co-evolve. Residues mediating long-range interactions
      within the TIR domain of TRIF were identified using residue network analysis.
      CONCLUSIONS: Based on the results of the modelling and residue network analysis,
      we propose that the N-terminal domain binds to the BB loop region of the TIR
      domain, thereby preventing its homodimersation. The binding of TRIF to TLR3 or
      TRAM could induce a slight conformational change, causing the interactions
      between the N-terminal domain and TIR domain to disrupt, thereby exposing the BB
      loop and rendering it amenable for higher-order oligomerisation. REVIEWERS: This
      article was reviewed by Michael Gromiha, Srikrishna Subramaniam and Peter Bond
      (nominated by Chandra Verma).

PMID- 28427454
TI  - Cryptosporidium and Giardia in Africa: current and future challenges.
AB  - Cryptosporidium and Giardia are important causes of diarrhoeal illness. Adequate
      knowledge of the molecular diversity and geographical distribution of these
      parasites and the environmental and climatic variables that influence their
      prevalence is important for effective control of infection in at-risk
      populations, yet relatively little is known about the epidemiology of these
      parasites in Africa. Cryptosporidium is associated with moderate to severe
      diarrhoea and increased mortality in African countries and both parasites
      negatively affect child growth and development. Malnutrition and HIV status are
      also important contributors to the prevalence of Cryptosporidium and Giardia in
      African countries. Molecular typing of both parasites in humans, domestic animals
      and wildlife to date indicates a complex picture of both anthroponotic, zoonotic
      and spill-back transmission cycles that requires further investigation. For
      Cryptosporidium, the only available drug (nitazoxanide) is ineffective in HIV and
      malnourished individuals and therefore more effective drugs are a high priority.
      Several classes of drugs with good efficacy exist for Giardia, but dosing
      regimens are suboptimal and emerging resistance threatens clinical utility.
      Climate change and population growth are also predicted to increase both
      malnutrition and the prevalence of these parasites in water sources. Dedicated
      and co-ordinated commitments from African governments involving "One Health"
      initiatives with multidisciplinary teams of veterinarians, medical workers,
      relevant government authorities, and public health specialists working together
      are essential to control and prevent the burden of disease caused by these
      parasites.

PMID- 28427458
TI  - Whole-exome sequencing identifies novel candidate predisposition genes for
      familial polycythemia vera.
AB  - BACKGROUND: Polycythemia vera (PV), characterized by massive production of
      erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a
      somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe), leading to
      constitutive activation of JAK-STAT signaling pathway. Familial clustering is
      also observed occasionally, but high-penetrance predisposition genes to PV have
      remained unidentified. RESULTS: We studied the predisposition to PV by exome
      sequencing (three cases) in a Finnish PV family with four patients. The 12 shared
      variants (maximum allowed minor allele frequency <0.001 in Finnish population in
      ExAC database) predicted damaging in silico and absent in an additional control
      set of over 500 Finns were further validated by Sanger sequencing in a fourth
      affected family member. Three novel predisposition candidate variants were
      identified: c.1254C > G (p.Phe418Leu) in ZXDC, c.1931C > G (p.Pro644Arg) in ATN1,
      and c.701G > A (p.Arg234Gln) in LRRC3. We also observed a rare, predicted benign
      germline variant c.2912C > G (p.Ala971Gly) in BCORL1 in all four patients.
      Somatic mutations in BCORL1 have been reported in myeloid malignancies. We
      further screened the variants in eight PV patients in six other Finnish families,
      but no other carriers were found. CONCLUSIONS: Exome sequencing provides a
      powerful tool for the identification of novel variants, and understanding the
      familial predisposition of diseases. This is the first report on Finnish familial
      PV cases, and we identified three novel candidate variants that may predispose to
      the disease.

PMID- 28427460
TI  - Significance of spatial organization of chromosomes in the progression of acute
      myeloid leukemia.

PMID- 28427459
TI  - Subjective perceived impact of Tai Chi training on physical and mental health
      among community older adults at risk for ischemic stroke: a qualitative study.
AB  - BACKGROUND: Evidence from quantitative studies suggest that Tai Chi produces a
      variety of health-related benefits, but few qualitative studies have investigated
      how older adults perceive the benefit of Tai Chi. The objective of the current
      study was to qualitatively evaluate the perceived benefits of Tai Chi practice
      among community older population. METHODS: This study was conducted with
      participants from a trial examining the effects of a 12-week Tai Chi training on
      ischemic stroke risk in community older adults (n = 170). A total of 20
      participants were randomly selected from a convenience sample of participants who
      had completed 12-week Tai Chi training (n = 68) were interviewed regarding their
      perceived benefit on physical and mental health and whether Tai Chi exercise was
      suitable for the elderly. RESULTS: All participants agreed that Tai Chi training
      could relax their body and make them comfortable. Most of them thought Tai Chi
      training could promote physical health, including relieving pain, enhancing
      digestion, strengthening immunity, enhancing energy and improving sleep quality,
      enhancing their mental and emotional state (e.g. improving mood and reducing
      anxiety, improving concentration and promoting interpersonal relationship). Most
      of participants also agreed that Tai Chi exercise was appropriate for community
      older people. Three primary themes emerged from content analysis: Improving
      physical health; Enhancing mental and emotional state; Conforming with the
      request of the elderly. CONCLUSION: The findings indicate that regular Tai Chi
      exercise may have positive benefits in terms of improved physical health and
      mental state among community elderly population, and may be useful and feasible
      body-mind exercise to community elderly population for its positive effects and
      advantages. TRIAL REGISTRATION: ChiCTR ChiCTR-TRC-13003601 . Registered 23 July
      2014.

PMID- 28427461
TI  - Inhibitory activities of selected Sudanese medicinal plants on Porphyromonas
      gingivalis and matrix metalloproteinase-9 and isolation of bioactive compounds
      from Combretum hartmannianum (Schweinf) bark.
AB  - BACKGROUND: Periodontal diseases are one of the major health problems and among
      the most important preventable global infectious diseases. Porphyromonas
      gingivalis is an anaerobic Gram-negative bacterium which has been strongly
      implicated in the etiology of periodontitis. Additionally, matrix
      metalloproteinases-9 (MMP-9) is an important factor contributing to periodontal
      tissue destruction by a variety of mechanisms. The purpose of this study was to
      evaluate the selected Sudanese medicinal plants against P. gingivalis bacteria
      and their inhibitory activities on MMP-9. METHODS: Sixty two methanolic and 50%
      ethanolic extracts from 24 plants species were tested for antibacterial activity
      against P. gingivalis using microplate dilution assay method to determine the
      minimum inhibitory concentration (MIC). The inhibitory activity of seven methanol
      extracts selected from the 62 extracts against MMP-9 was determined by
      Colorimetric Drug Discovery Kit. In search of bioactive lead compounds, Combretum
      hartmannianum bark which was found to be within the most active plant extracts
      was subjected to various chromatographic (medium pressure liquid chromatography,
      column chromatography on a Sephadex LH-20, preparative high performance liquid
      chromatography) and spectroscopic methods (liquid chromatography-mass
      spectrometry, Nuclear Magnetic Resonance (NMR)) to isolate and characterize
      flavogalonic acid dilactone and terchebulin as bioactive compounds. RESULTS:
      About 80% of the crude extracts provided a MIC value <=4 mg/ml against bacteria.
      The extracts which revealed the highest potency were: methanolic extracts of
      Terminalia laxiflora (wood; MIC = 0.25 mg/ml) followed by Acacia totrtilis
      (bark), Ambrosia maritima (aerial part), Argemone mexicana (seed), C.
      hartmannianum (bark), Terminalia brownii (wood) and 50% ethanolic extract of T.
      brownii (bark) with MIC values of 0.5 mg/ml. T. laxiflora (wood) and C.
      hartmannianum (bark) which belong to combretaceae family showed an inhibitory
      activity over 50% at the concentration of 10 MUg/ml against MMP-9. Additionally,
      MMP-9 was significantly inhibited by terchebulin with IC50 value of 6.7 MUM.
      CONCLUSIONS: To the best of our knowledge, flavogalonic acid dilactone and
      terchebulin were isolated from C. hartmannianium bark for the first time in this
      study. Because of terchebulin and some crude extracts acting on P. gingivalis
      bacteria and MMP-9 enzyme that would make them promising natural preference for
      preventing and treating periodontal diseases.

PMID- 28427462
TI  - Within-person associations of young adolescents' physical activity across five
      primary locations: is there evidence of cross-location compensation?
AB  - BACKGROUND: Youth are active in multiple locations, but it is unknown whether
      more physical activity in one location is associated with less in other
      locations. This cross-sectional study examines whether on days with more physical
      activity in a given location, relative to their typical activity in that
      location, youth had less activity in other locations (i.e., within-person
      associations/compensation). METHODS: Participants were 528 adolescents, ages 12
      to 16 (M = 14.12, SD = 1.44, 50% boys, 70% White non-Hispanic). Accelerometer and
      Global Positioning System devices were used to measure the proportion of time
      spent in moderate-to-vigorous physical activity (MVPA) in five locations: home,
      home neighborhood, school, school neighborhood, and other locations. Mixed
      effects regression was used to examine within-person associations of MVPA across
      locations and moderators of these associations. RESULTS: Two of ten within
      participant associations tested indicated small amounts of compensation, and one
      association indicated generalization across locations. Higher at-school MVPA
      (relative to the participant's average) was related to less at-home MVPA and
      other-location MVPA (Bs = -0.06 min/day). Higher home-neighborhood MVPA (relative
      to the participant's average) was related to more at-home MVPA (B = 0.07
      min/day). Some models showed that compensation was more likely (or generalization
      less likely) in boys and non-whites or Hispanic youth. CONCLUSIONS: Consistent
      evidence of compensation across locations was not observed. A small amount of
      compensation was observed for school physical activity, suggesting that
      adolescents partially compensated for high amounts of school activity by being
      less active in other locations. Conversely, home-neighborhood physical activity
      appeared to carry over into the home, indicating a generalization effect. Overall
      these findings suggest that increasing physical activity in one location is
      unlikely to result in meaningful decreases in other locations. Supporting
      physical activity across multiple locations is critical to increasing overall
      physical activity in youth.

PMID- 28427463
TI  - Combination of sofosbuvir, pegylated-interferon and ribavirin for treatment of
      hepatitis C virus genotype 1 infection: a systematic review and meta-analysis.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is an important cause of chronic
      liver disease which has been affected 3% of world's population. Some studies have
      shown that adding Sofosbuvir (SOF), an HCV polymerase inhibitor to the
      conventional therapy of Pegylated-interferon (PegIFN) plus Ribavirin (RBV) can
      increase the rate of sustained virologic response (SVR) among HCV-infected
      patients. This study was conducted to determine the effect of combination therapy
      with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection using
      systematic review with meta-analysis. METHODS: In this study, electronic
      databases including PubMed, Scopus, Science Direct, and Web of Science were
      comprehensively searched using appropriate strategies containing all related
      keywords of "hepatitis C", "PegIFN", "RBV" and "SOF". Studies assessed the
      efficacy of combination therapy with PegIFN and RBV plus SOF for chronic
      hepatitis C genotype 1 infection were included in the meta-analysis. RESULTS:
      After screening of 757 records, we included five articles with total sample size
      of 411 to the meta-analysis. Based on the fixed-effect model (chi 2 = 5.29, P =
      0.26 and I2 = 24.4%), pooled SVR rate for treatment regimen of PegIFN and RBV
      plus SOF was calculated as 88.54% (95% CI = 85.77%-91.32%). CONCLUSIONS:
      Combination therapy with PegIFN and RBV plus SOF results in high treatment
      response in patients with HCV genotype 1 infection.

PMID- 28427464
TI  - Accuracy of low-density lipoprotein cholesterol estimation at very low levels.
AB  - BACKGROUND: As the approach to low-density lipoprotein cholesterol (LDL-C)
      lowering becomes increasingly intensive, accurate assessment of LDL-C at very low
      levels warrants closer attention in individualized clinical efficacy and safety
      evaluation. We aimed to assess the accuracy of LDL-C estimation at very low
      levels by the Friedewald equation, the de facto clinical standard, and compare
      its accuracy with a novel, big data-derived LDL-C estimate. METHODS: In 191,333
      individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of
      Friedewald and novel LDL-C values in relation to direct measurements by Vertical
      Auto Profile ultracentrifugation. We examined differences (estimate minus
      ultracentrifugation) and classification according to levels initiating additional
      safety precautions per clinical practice guidelines. RESULTS: Friedewald values
      were less than ultracentrifugation measurement, with a median difference (25th to
      75th percentile) of -2.4 (-7.4 to 0.6) at 50-69 mg/dL, -7.0 (-16.2 to -1.2) at 25
      39 mg/dL, and -29.0 (-37.4 to -19.6) at < 15 mg/dL. The respective values by
      novel estimation were -0.1 (-1.5 to 1.3), -1.1 (-2.5 to 0.3), and -2.7 (-4.9 to
      0.0) mg/dL. Among those with Friedewald LDL-C < 15, 15 to < 25, and 25 to < 40
      mg/dL, the classification was discordantly low in 94.9%, 82.6%, and 59.9% of
      individuals as compared with 48.3%, 42.4%, and 22.4% by novel estimation.
      CONCLUSIONS: Estimation of even lower LDL-C values (by Friedewald and novel
      methods) is even more inaccurate. More often than not, a Friedewald value < 40
      mg/dL is underestimated, which translates into unnecessary safety alarms that
      could be reduced in half by estimation using our novel method.

PMID- 28427465
TI  - The use of evidence in English local public health decision-making: a systematic
      scoping review.
AB  - BACKGROUND: Public health decision-making structures in England have transformed
      since the implementation of reforms in 2013, with responsibility for public
      health services and planning having shifted from the "health" boundary to local
      authority (LA; local government) control. This transformation may have
      interrupted flows of research evidence use in decision-making and introduced a
      new political element to public health decision-making. For generators of
      research evidence, understanding and responding to this new landscape and
      decision-makers' evidence needs is essential. METHODS: We conducted a systematic
      scoping review of the literature, drawing upon four databases and undertaking
      manual searching and citation tracking. Included studies were English-based,
      published in 2010 onwards, and were focused on public health decision-making,
      including the utilisation or underutilisation of research evidence use, in local
      (regional or sub-regional) areas. All studies presented empirical findings
      collected through primary research methods or through the reanalysis of existing
      primary data. RESULTS: From a total of 903 records, 23 papers from 21 studies
      were deemed to be eligible and were included for further data extraction. Three
      clear trends in evidence use were identified: (i) the primacy of local evidence,
      (ii) the important role of local experts in providing evidence and knowledge, and
      (iii) the high value placed on local evaluation evidence despite the varying
      methodological rigour. Barriers to the use of research evidence included issues
      around access and availability of applicable research evidence, and indications
      that the use of evidence could be perceived as a bureaucratic process. Two new
      factors resulting from reforms to public health structures were identified that
      potentially changed existing patterns of research evidence use and decision
      making requirements: (i) greater emphasis among public health practitioners on
      the perceived uniqueness of LA areas and structures following devolution of
      public health into LAs and (ii) challenges introduced in responding to higher
      levels of local political accountability. CONCLUSIONS: There is a need to better
      understand and respond to the evidence needs of decision-makers working in public
      health and to work more collaboratively in developing solutions to the
      underutilisation of research evidence in decision-making.

PMID- 28427466
TI  - Determinants of orphan drugs prices in France: a regression analysis.
AB  - BACKGROUND: The introduction of the orphan drug legislation led to the increase
      in the number of available orphan drugs, but the access to them is often limited
      due to the high price. Social preferences regarding funding orphan drugs as well
      as the criteria taken into consideration while setting the price remain unclear.
      The study aimed at identifying the determinant of orphan drug prices in France
      using a regression analysis. METHODS: All drugs with a valid orphan designation
      at the moment of launch for which the price was available in France were included
      in the analysis. The selection of covariates was based on a literature review and
      included drug characteristics (Anatomical Therapeutic Chemical (ATC) class,
      treatment line, age of target population), diseases characteristics (severity,
      prevalence, availability of alternative therapeutic options), health technology
      assessment (HTA) details (actual benefit (AB) and improvement in actual benefit
      (IAB) scores, delay between the HTA and commercialisation), and study
      characteristics (type of study, comparator, type of endpoint). The main data
      sources were European public assessment reports, HTA reports, summaries of
      opinion on orphan designation of the European Medicines Agency, and the French
      insurance database of drugs and tariffs. A generalized regression model was
      developed to test the association between the annual treatment cost and selected
      covariates. RESULTS: A total of 68 drugs were included. The mean annual treatment
      cost was ?96,518. In the univariate analysis, the ATC class (p = 0.01),
      availability of alternative treatment options (p = 0.02) and the prevalence (p =
      0.02) showed a significant correlation with the annual cost. The multivariate
      analysis demonstrated significant association between the annual cost and
      availability of alternative treatment options, ATC class, IAB score, type of
      comparator in the pivotal clinical trial, as well as commercialisation date and
      delay between the HTA and commercialisation. CONCLUSION: The orphan drug pricing
      is a multivariate phenomenon. The complex association between drug prices and the
      studied attributes and shows that payers integrate multiple variables in decision
      making when setting orphan drug prices. The interpretation of the study results
      is limited by the small sample size and the complex data structure.

PMID- 28427467
TI  - Coenzyme Q10 prevents oxidative stress and fibrosis in isoprenaline induced
      cardiac remodeling in aged rats.
AB  - BACKGROUND: The objective of the present study aimed to investigate the effect of
      CoQ10 treatment on isoprenaline (ISO)-induced cardiac remodeling in rats.
      METHODS: Rats were divided into three groups namely Control group, ISO treated
      group and CoQ10 + ISO treated group, each consisting of 6 rats. The cardiac
      specific CK-MB, AST, ALT activity and other oxidative stress parameters were
      estimated in heart and kidneys. Additionally histological examination was also
      performed to visualize the inflammatory cells infiltration and fibrosis in both
      tissues. RESULTS: Administration of ISO resulted in an increase in the heart-to
      body weight (HW/BW) ratio and an also increased the serum CK-MB, AST and ALT
      enzyme activity. Serum levels of lipid peroxidation products, and oxidative
      stress markers showed significant increase in ISO-treated rats. Histopathological
      examination of heart tissue revealed focal areas of endocardium degeneration,
      mononuclear cells infiltration, fibrous tissue deposition, and increased
      thickness of the myocardium of left ventricle. Similar degeneration was also
      found in kidneys. Treatment with CoQ10 (100 mg/kg) significantly improved the
      oxidative stresses in ISO treated rats. Moreover, CoQ10 treatment prevented
      inflammatory cells infiltration and reduced fibrosis in ISO administered rats.
      CONCLUSION: In conclusion, our study provides evidence that CoQ10 may prevent the
      development of cardiac remodeling, and fibrosis in ISO administered rats.

PMID- 28427468
TI  - Learning from biomedical linked data to suggest valid pharmacogenes.
AB  - BACKGROUND: A standard task in pharmacogenomics research is identifying genes
      that may be involved in drug response variability, i.e., pharmacogenes. Because
      genomic experiments tended to generate many false positives, computational
      approaches based on the use of background knowledge have been proposed. Until
      now, only molecular networks or the biomedical literature were used, whereas many
      other resources are available. METHOD: We propose here to consume a diverse and
      larger set of resources using linked data related either to genes, drugs or
      diseases. One of the advantages of linked data is that they are built on a
      standard framework that facilitates the joint use of various sources, and thus
      facilitates considering features of various origins. We propose a selection and
      linkage of data sources relevant to pharmacogenomics, including for example
      DisGeNET and Clinvar. We use machine learning to identify and prioritize
      pharmacogenes that are the most probably valid, considering the selected linked
      data. This identification relies on the classification of gene-drug pairs as
      either pharmacogenomically associated or not and was experimented with two
      machine learning methods -random forest and graph kernel-, which results are
      compared in this article. RESULTS: We assembled a set of linked data relative to
      pharmacogenomics, of 2,610,793 triples, coming from six distinct resources.
      Learning from these data, random forest enables identifying valid pharmacogenes
      with a F-measure of 0.73, on a 10 folds cross-validation, whereas graph kernel
      achieves a F-measure of 0.81. A list of top candidates proposed by both
      approaches is provided and their obtention is discussed.

PMID- 28427469
TI  - Graves' orbitopathy as a rare disease in Europe: a European Group on Graves'
      Orbitopathy (EUGOGO) position statement.
AB  - BACKGROUND: Graves' orbitopathy (GO) is an autoimmune condition, which is
      associated with poor clinical outcomes including impaired quality of life and
      socio-economic status. Current evidence suggests that the incidence of GO in
      Europe may be declining, however data on the prevalence of this disease are
      sparse. Several clinical variants of GO exist, including euthyroid GO, recently
      listed as a rare disease in Europe (ORPHA466682). The objective was to estimate
      the prevalence of GO and its clinical variants in Europe, based on available
      literature, and to consider whether they may potentially qualify as rare. Recent
      published data on the incidence of GO and Graves' hyperthyroidism in Europe were
      used to estimate the prevalence of GO. The position statement was developed by a
      series of reviews of drafts and electronic discussions by members of the European
      Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000
      persons. The prevalence of other clinical variants is also low: hypothyroid GO
      0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with
      acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50
      1.50/10,000. CONCLUSION: GO has a prevalence that is clearly above the threshold
      for rarity in Europe. However, each of its clinical variants have a low
      prevalence and could potentially qualify for being considered as a rare
      condition, providing that future research establishes that they have a distinct
      pathophysiology. EUGOGO considers this area of academic activity a priority.

PMID- 28427470
TI  - Pulmonary hypertension in lymphangioleiomyomatosis: prevalence, severity and the
      role of carbon monoxide diffusion capacity as a screening method.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is included within group 5 of the
      current PH classification (unclear multifactorial mechanisms). However, data
      regarding the occurrence of PH in LAM are scarce. The aims of the study were to
      describe the prevalence and characteristics of PH in a large cohort of LAM
      patients with different levels of severity, and to evaluate the role of
      echocardiography and carbon monoxide diffusion capacity (DLCO) as screening
      methods for PH in LAM. METHODS: One hundred five LAM patients underwent
      transthoracic echocardiography, pulmonary function tests (PFTs) and 6-min walk
      test (6MWT). Patients with a suspicion of PH on echocardiography, defined by the
      presence of estimated systolic pulmonary artery pressure (PAP) over 35 mmHg or
      PFT showing DLco below 40% of the predicted value, underwent right heart
      catheterisation to confirm the diagnosis of PH. RESULTS: Eight patients (7.6%)
      had PH confirmed on right heart catheterisation, six patients (5.7%) had a pre
      capillary pattern and two patients (1.9%) had a post-capillary profile. Only one
      patient (1%) had mean PAP over 35 mmHg. Patients with PH had lower FEV1 and DLCO
      in PFTs and greater oxygen desaturation and dyspnea intensity during 6MWT
      compared with those without PH. In 63% of the patients with confirmed PH, the
      right heart catheterisation was performed based only on DLCO result. CONCLUSIONS:
      The prevalence of PH is low in LAM patients. Pulmonary hypertension in LAM is
      typically mild and significantly associated with pulmonary parenchymal
      involvement. Carbon monoxide diffusion capacity significantly improved the
      identification of PH in LAM patients.

PMID- 28427471
TI  - Quality of life and healthcare service utilization among methadone maintenance
      patients in a mountainous area of Northern Vietnam.
AB  - BACKGROUND: The expansion of methadone maintenance treatment in mountainous areas
      in still limited and little is known about its health impacts on drug users. This
      study aimed to examine health-related quality of life (HRQOL) and health care
      access among patients engaging in methadone maintenance treatment (MMT) in Tuyen
      Quang, a mountainous province in Vietnam. METHODS: We conducted a cross-sectional
      survey with 241 patients conveniently recruited in two MMT clinics (Son Duong and
      Tuyen Quang). EuroQol-5 Dimensions - 5 levels (EQ-5D-5 L) and Visual analogue
      scale (VAS) were employed to measure HRQOL. Multivariate logistic and tobit
      regressions were used to determine the factors associated with HRQOL and health
      care utilization. RESULTS: The overall mean score of the EQ-5D index and EQ-VAS
      were 0.88 (SD = 0.20) and 81.8% (SD = 15.27%), respectively. Only 8.7% utilized
      inpatient services, and 14.9% used outpatient services. Being more highly
      educated, suffering acute diseases, and using health service within the last 12
      months were associated with a decreased EQ-5D index. Individuals who were
      multiple substance abusers and those who recently had inpatient care were more
      likely to have a lower VAS. Older respondents, those taking their medications at
      the more impoverished clinic, substance abusers, and individuals who were
      struggling with anxiety/depression or their usual daily activities were more
      likely to use both inpatient and outpatient care. CONCLUSIONS: In summary, we
      observed good HRQOL, but high prevalence of anxiety/depression and low rates of
      service utilization among MMT patients in Tuyen Quang province. To improve the
      outcomes of MMT services in mountainous areas, it is necessary to introduce
      personalized and integrative services models with counseling and interventions on
      multiple substance use.

PMID- 28427472
TI  - Optimising conservative management of chronic low back pain: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Lower back pain is a global health issue affecting approximately 80%
      of people at some stage in their life. The current literature suggests that any
      exercise is beneficial for reducing back pain. However, as pain is a subjective
      evaluation and physical deficits are evident in low back pain, using it as the
      sole outcome measure to evaluate superiority of an exercise protocol for low back
      pain treatment is insufficient. The overarching goal of the current clinical
      trial is to implement two common, conservative intervention approaches and
      examine their impact on deficits in chronic low back pain. METHODS/DESIGN: Forty
      participants, 25-45 years old with chronic (>3 months), non-specific low back
      pain will be recruited. Participants will be randomised to receive either motor
      control and manual therapy (n = 20) or general strength and conditioning (n = 20)
      exercise treatments for 6 months. The motor control/manual therapy group will
      receive twelve 30-min sessions, ten in the first 3 months (one or two per week)
      and two in the last 3 months. The general exercise group will attend two 1-hour
      sessions weekly for 3 months, and one or two a week for the following 3 months.
      Primary outcome measures are average lumbar spine intervertebral disc T2
      relaxation time and changes in thickness of the transversus abdominis muscle on a
      leg lift using magnetic resonance imaging (MRI). Secondary outcomes include
      muscle size and fat content, vertebral body fat content, intervertebral disc
      morphology and water diffusion measured by MRI, body composition using dual
      energy X-ray absorptiometry, physical function through functional tests, changes
      in corticospinal excitability and cortical motor representation of the spinal
      muscles using transcranial magnetic stimulation and self-reported measure of pain
      symptoms, health and disability. Outcome measures will be conducted at baseline,
      at the 3-month follow-up and at 6 months at the end of intervention. Pain,
      depressive symptomology and emotions will be captured fortnightly by
      questionnaires. DISCUSSION: Chronic low back pain is ranked the highest disabling
      disorder in Australia. The findings of this study will inform clinical practice
      guidelines to assist with decision-making approaches where outcomes beyond pain
      are sought for adults with chronic low back pain. TRIAL REGISTRATION: Australian
      New Zealand Clinical Trials Registry, ACTRN12615001270505 . Registered on 20
      November 2015.

PMID- 28427474
TI  - Assessment of surgical antimicrobial prophylaxis in Orthopaedics and Traumatology
      Surgical Unit of a Tertiary Care Teaching Hospital in Addis Ababa.
AB  - BACKGROUND: Prophylactic antimicrobials have a starring role in prevention of
      surgical site infection. This study assesses the practice of surgical
      antimicrobial prophylaxis (SAP) and development of surgical site infection (SSI)
      based on patient chart review in patients who underwent surgery in the
      Orthopaedics and Traumatology Surgical Unit of Tikur Anbesa Specialized Hospital
      (TASH). RESULTS: Majority of the patients 144 (72%) were males. 108 (54%) of the
      surgical wounds were clean and 63 (31%) were clean contaminated. 160 (80%)
      patients received preoperative prophylaxis, of these 153 (96%) received
      postoperative prophylaxis as well. 34 (17%) patients did not receive preoperative
      antimicrobial prophylaxis, while 6 (3%) patients had no record about preoperative
      antimicrobial prophylaxis. Among those who received preoperative antimicrobial
      prophylaxis the time of administration was not recorded in 87 (54%) of the
      patient charts and 36 (23%) patients had preoperative antimicrobial prophylaxis
      greater than 2 h prior to incision. Among the 188 (94%) patients that received
      postoperative antimicrobial prophylaxis; the duration of administration was more
      than 72 h in 114 (61%) patients, while only 8 (4%) received for less than 24 h
      after surgery. Ceftriaxone 309 (70%) was the most prescribed agent for
      prophylaxis. 32 (16%) patients developed surgical site of infection. Using odds
      ratio age equal to or above 50, clean contaminated and contaminated surgical
      wounds were not statistically associated with increased risk of SSI. CONCLUSION:
      Most patients who underwent surgery received prophylactic antimicrobials;
      nevertheless, the practice was not aligned with standard guidelines'
      recommendations and patients developed surgical site infections.

PMID- 28427473
TI  - Intestinal Behcet and Crohn's disease: two sides of the same coin.
AB  - Behcet's disease (BD) and Crohn's disease (CD) are chronic immune-mediated,
      inflammatory disorders affecting many different systems (joints, skin, eyes,
      gastrointestinal and biliary tracts). Both disorders have fluctuating courses and
      when gastrointestinal symptoms are prevalent, differential diagnosis can be
      difficult. BD involves the gastrointestinal tract in 10-15% of cases with
      localized lesions in the ileocecal region. The clinical picture is heterogeneous
      with various clusters of disease expression. CD is a chronic inflammatory
      disorder, which can affect any part of the intestinal tract, as well as extra
      intestinal tissue. Factors that contribute towards the pathogenesis of both
      disease include the host's genetic profile, and immune system, and environmental
      factors such as the gut microbiota. The aim of this manuscript is to provide a
      narrative review of clinical features of BD and CD, highlighting the importance
      of differential diagnosis and therapeutic approach, especially in the presence of
      gastrointestinal involvement. A comprehensive search of published literature
      using the Pubmed ( http://www.ncbi.nlm.nih.gov/pubmed/ ) database was carried out
      to identify all articles published in English from 1999 to October 2016, using 4
      key terms: "Behcet Disease", "Intestinal Behcet's Disease", "Crohn's Disease"
      and" Inflammatory Bowel Disease".

PMID- 28427475
TI  - Protocol: a systematic review of studies developing and/or evaluating search
      strategies to identify prognosis studies.
AB  - BACKGROUND: Prognosis research is on the rise, its importance recognised because
      chronic health conditions and diseases are increasingly common and costly.
      Prognosis systematic reviews are needed to collate and synthesise these research
      findings, especially to help inform effective clinical decision-making and
      healthcare policy. A detailed, comprehensive search strategy is central to any
      systematic review. However, within prognosis research, this is challenging due to
      poor reporting and inconsistent use of available indexing terms in electronic
      databases. Whilst many published search filters exist for finding clinical
      trials, this is not the case for prognosis studies. This systematic review aims
      to identify and compare existing methodological filters developed and evaluated
      to identify prognosis studies of any of the three main types: overall prognosis,
      prognostic factors, and prognostic [risk prediction] models. METHODS: Primary
      studies reporting the development and/or evaluation of methodological search
      filters to retrieve any type of prognosis study will be included in this
      systematic review. Multiple electronic bibliographic databases will be searched,
      grey literature will be sought from relevant organisations and websites, experts
      will be contacted, and citation tracking of key papers and reference list
      checking of all included papers will be undertaken. Titles will be screened by
      one person, and abstracts and full articles will be reviewed for inclusion
      independently by two reviewers. Data extraction and quality assessment will also
      be undertaken independently by two reviewers with disagreements resolved by
      discussion or by a third reviewer if necessary. Filters' characteristics and
      performance metrics reported in the included studies will be extracted and
      tabulated. To enable comparisons, filters will be grouped according to database,
      platform, type of prognosis study, and type of filter for which it was intended.
      DISCUSSION: This systematic review will identify all existing validated prognosis
      search filters and synthesise evidence about their applicability and performance.
      These findings will identify if current filters provide a proficient means of
      searching electronic bibliographic databases or if further prognosis filters are
      needed and can feasibly be developed for systematic searches of prognosis
      studies.

PMID- 28427476
TI  - Regeneration of full-thickness skin defects by differentiated adipose-derived
      stem cells into fibroblast-like cells by fibroblast-conditioned medium.
AB  - BACKGROUND: Fibroblasts are ubiquitous cells in the human body and are absolutely
      necessary for wound healing such as for injured skin. This role of fibroblasts
      was the reason why we aimed to differentiate human adipose-derived stem cells
      (hADSCs) into fibroblasts and to test their wound healing potency. Recent reports
      on hADSC-derived conditioned medium have indicated stimulation of collagen
      synthesis as well as migration of dermal fibroblasts in wound sites with these
      cells. Similarly, human fibroblast-derived conditioned medium (F-CM) was reported
      to contain a variety of factors known to be important for growth of skin.
      However, it remains unknown whether and how F-CM can stimulate hADSCs to secrete
      type I collagen. METHODS: In this study, we obtained F-CM from the culture of
      human skin fibroblast HS27 cells in DMEM media. For an in-vivo wound healing
      assay using cell transplantation, balb/c nude mice with full-thickness skin wound
      were used. RESULTS: Our data showed that levels of type I pro-collagen secreted
      by hADSCs cultured in F-CM increased significantly compared with hADSCs kept in
      normal medium for 72 h. In addition, from a Sircol collagen assay, the amount of
      collagen in F-CM-treated hADSC conditioned media (72 h) was markedly higher than
      both the normal medium-treated hADSC conditioned media (72 h) and the F-CM (24
      h). We aimed to confirm that hADSCs in F-CM would differentiate into fibroblast
      cells in order to stimulate wound healing in a skin defect model. To investigate
      whether F-CM induced hADSCs into fibroblast-like cells, we performed FACS
      analysis and verified that both F-CM-treated hADSCs and HS27 cells contained
      similar expression patterns for CD13, CD54, and CD105, whereas normal medium
      treated hADSCs were significantly different. mRNA level  analysis for Nanog,
      Oct4A, and Sox2 as undifferentiation markers and vimentin, HSP47, and desmin as
      matured fibroblast markers supported the characterization that hADSCs in F-CM
      were highly differentiated into fibroblast-like cells. To discover the mechanism
      of type I pro-collagen expression in hADSCs in F-CM, we observed that phospho
      smad 2/3 levels were increased in the TGF-beta/Smad signaling pathway. For in
      vivo analysis, we injected various cell types into balb/c nude mouse skin
      carrying a 10-mm punch wound, and observed a significantly positive wound healing
      effect in this full-thickness excision model with F-CM-treated hADSCs rather than
      with untreated hADSCs or the PBS injected group. CONCLUSIONS: We differentiated F
      CM-treated hADSCs into fibroblast-like cells and demonstrated their efficiency in
      wound healing in a skin wound model.

PMID- 28427477
TI  - Plasma chitotriosidase activity versus CCL18 level for assessing type I Gaucher
      disease severity: protocol for a systematic review with meta-analysis of
      individual participant data.
AB  - BACKGROUND: Gaucher disease (GD) is an autosomal recessive lysosomal storage
      disorder caused by deficiency in acid beta-glucosidase. GD exhibits a wide
      clinical spectrum of disease severity with an unpredictable natural course.
      Plasma chitotriosidase activity and CC chemokine ligand 18 (CCL18) have been
      exchangeably used for monitoring GD activity and response to enzyme replacement
      therapy in conjunction with clinical assessment. Yet, a large-scale head-to-head
      comparison of these two biomarkers is currently lacking. We propose a
      collaborative systematic review with meta-analysis of individual participant data
      (IPD) to compare the accuracy of plasma chitotriosidase activity and CCL18 in
      assessing type I (i.e., non-neuropathic) GD severity. METHODS: Eligible studies
      include cross-sectional, cohort, and randomized controlled studies recording both
      plasma chitotriosidase activity and CCL18 level at baseline and/or at follow-up
      in consecutive children or adult patients with type I GD. Pre-specified surrogate
      outcomes reflecting GD activity include liver and spleen volume, hemoglobin
      concentration, platelet count, and symptomatic bone events with imaging
      confirmation. Primary studies will be identified by searching Medline (1995
      onwards), EMBASE (1995 onwards), and Cochrane Central Register of Controlled
      Trials (CENTRAL). Electronic search will be complemented by contacting research
      groups in order to identify unpublished relevant studies. Where possible, IPD
      will be extracted from published articles. Corresponding authors will be invited
      to collaborate by supplying IPD. The methodological quality of retrieved studies
      will be appraised for each study outcome, using a checklist adapted from the
      Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcome
      will be a composite of liver volume >1.25 multiple of normal (MN), spleen volume
      >5 MN, hemoglobin concentration <11 g/dL, or platelet count <100 * 109/L. Effect
      size estimates for biomarker comparative accuracy in predicting outcomes will be
      reported as differences in areas under receiver operating characteristic curves
      along with 95% confidence intervals. Effect size estimates will be reported as
      (weighted) mean differences along with 95% confidence intervals for each
      biomarker according to outcomes. IPD meta-analysis will be conducted with both
      one- and two-stage approaches. DISCUSSION: Valid and precise accuracy estimates
      will be derived for CCL18 relative to plasma chitotriosidase activity in
      discriminating patients according to GD severity. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO 2015 CRD42015027243.

PMID- 28427479
TI  - Mainstreaming gender and promoting intersectionality in Papua New Guinea's health
      policy: a triangulated analysis applying data-mining and content analytic
      techniques.
AB  - BACKGROUND: Gender mainstreaming is an approach to policy and planning that
      emphasizes equality between the sexes. It is the stated policy for gender equity
      in Papua New Guinea's (PNG) health sector, as well as all other sectors, and is
      enshrined in the policies of its biggest aid givers. However, there is criticism
      that gender mainstreaming's application has too often been technocratic and
      lacking in conceptual clarity not only in PNG but elsewhere. In the health sector
      this is further exacerbated by a traditional bio-medical approach, which is often
      paternalistic and insufficiently patient- and family-centered. METHODS: This
      study analyses the policy attitudes toward gender in PNG's health sector using
      both data-mining and a traditional, summative content analysis. RESULTS: Our
      results show that gender is rarely mentioned. When it is, it is most often
      mentioned in relation to programs such as maternity and childcare for women, and
      elsewhere is applied technocratically. CONCLUSION: For PNG to promote greater
      levels of equity, the focus should first be on conceptualizing gender in a way
      that is meaningful for Papuans, taking into account the diversity of experiences
      and setting. Second, there should be greater focus on activists and civil society
      groups as the stakeholders most likely to make a difference in gender equity.

PMID- 28427478
TI  - Morphological and molecular characteristics of Malayfilaria sofiani Uni, Mat Udin
      & Takaoka n. g., n. sp. (Nematoda: Filarioidea) from the common treeshrew Tupaia
      glis Diard & Duvaucel (Mammalia: Scandentia) in Peninsular Malaysia.
AB  - BACKGROUND: The filarial nematodes Wuchereria bancrofti (Cobbold, 1877), Brugia
      malayi (Brug, 1927) and B. timori Partono, Purnomo, Dennis, Atmosoedjono,
      Oemijati & Cross, 1977 cause lymphatic diseases in humans in the tropics, while
      B. pahangi (Buckley & Edeson, 1956) infects carnivores and causes zoonotic
      diseases in humans in Malaysia. Wuchereria bancrofti, W. kalimantani Palmieri,
      Pulnomo, Dennis & Marwoto, 1980 and six out of ten Brugia spp. have been
      described from Australia, Southeast Asia, Sri Lanka and India. However, the
      origin and evolution of the species in the Wuchereria-Brugia clade remain
      unclear. While investigating the diversity of filarial parasites in Malaysia, we
      discovered an undescribed species in the common treeshrew Tupaia glis Diard &
      Duvaucel (Mammalia: Scandentia). METHODS: We examined 81 common treeshrews from
      14 areas in nine states and the Federal Territory of Peninsular Malaysia for
      filarial parasites. Once any filariae that were found had been isolated, we
      examined their morphological characteristics and determined the partial sequences
      of their mitochondrial cytochrome c oxidase subunit 1 (cox1) and 12S rRNA genes.
      Polymerase chain reaction (PCR) products of the internal transcribed spacer 1
      (ITS1) region were then cloned into the pGEM-T vector, and the recombinant
      plasmids were used as templates for sequencing. RESULTS: Malayfilaria sofiani
      Uni, Mat Udin & Takaoka, n. g., n. sp. is described based on the morphological
      characteristics of adults and microfilariae found in common treeshrews from Jeram
      Pasu, Kelantan, Malaysia. The Kimura 2-parameter distance between the cox1 gene
      sequences of the new species and W. bancrofti was 11.8%. Based on the three gene
      sequences, the new species forms a monophyletic clade with W. bancrofti and
      Brugia spp. The adult parasites were found in tissues surrounding the lymph nodes
      of the neck of common treeshrews. CONCLUSIONS: The newly described species
      appears most closely related to Wuchereria spp. and Brugia spp., but differs from
      these in several morphological characteristics. Molecular analyses based on the
      cox1 and 12S rRNA genes and the ITS1 region indicated that this species differs
      from both W. bancrofti and Brugia spp. at the genus level. We thus propose a new
      genus, Malayfilaria, along with the new species M. sofiani.

PMID- 28427480
TI  - Lessons from a large trauma center: impact of blunt chest trauma in polytrauma
      patients-still a relevant problem?
AB  - BACKGROUND: Thoracic trauma is the third most common cause of death after
      abdominal injury and head trauma in polytrauma patients. The purpose of this
      study was to investigate epidemiological data, treatment and outcome of
      polytrauma patients with blunt chest trauma in order to help improve management,
      prevent complications and decrease polytrauma patients' mortality. METHODS: In
      this retrospective study we included all polytrauma patients with blunt chest
      trauma admitted to our tertiary care center emergency department for a 2-year
      period, from June 2012 until May 2014. Data collection included details of
      treatment and outcome. Patients with chest trauma and Injury Severity Score (ISS)
      >=18 and Abbreviated Injury Scale (AIS) >2 in more than one body region were
      included. RESULTS: A total of 110 polytrauma patients with blunt chest injury
      were evaluated. 82 of them were males and median age was 48.5 years. Car
      accidents, falls from a height and motorbike accidents were the most common
      causes (>75%) for blunt chest trauma. Rib fractures, pneumothorax and pulmonary
      contusion were the most common chest injuries. Most patients (64.5%) sustained a
      serious chest injury (AISthorax 3), 19.1% a severe chest injury (AISthorax 4) and
      15.5% a moderate chest injury (AISthorax 2). 90% of patients with blunt chest
      trauma were treated conservatively. Chest tube insertion was indicated in 54.5%
      of patients. The need for chest tube was significantly higher among the AISthorax
      4 group in comparison to the AIS groups 3 and 2 (p < 0.001). Also, admission to
      the ICU was directly related to the severity of the AISthorax (p < 0.001). The
      severity of chest trauma did not correlate with ICU length of stay, intubation
      days, complications or mortality. CONCLUSION: Although 84.5% of patients suffered
      from serious or even severe chest injury, neither in the conservative nor in the
      surgically treated group a significant impact of injury severity on ICU stay,
      intubation days, complications or mortality was observed. AISthorax was only
      related to the rate of chest tube insertions and ICU admission. Management with
      early chest tube insertion when necessary, pain control and chest physiotherapy
      resulted in good outcome in the majority of patients.

PMID- 28427481
TI  - Triage and the Lost Art of Decoding Vital Signs: Restoring Physiologically Based
      Triage Skills in Complex Humanitarian Emergencies.
AB  - Triage management remains a major challenge, especially in resource-poor settings
      such as war, complex humanitarian emergencies, and public health emergencies in
      developing countries. In triage it is often the disruption of physiology, not
      anatomy, that is critical, supporting triage methodology based on clinician
      assessed physiological parameters as well as anatomy and mechanism of injury. In
      recent times, too many clinicians from developed countries have deployed to
      humanitarian emergencies without the physical exam skills needed to assess
      patients without the benefit of remotely fed electronic monitoring, laboratory,
      and imaging studies. In triage, inclusion of the once-widely accepted and
      collectively taught "art of decoding vital signs" with attention to their
      character and meaning may provide clues to a patient's physiological state,
      improving triage sensitivity. Attention to decoding vital signs is not a triage
      methodology of its own or a scoring system, but rather a skill set that supports
      existing triage methodologies. With unique triage management challenges being
      raised by an ever-changing variety of humanitarian crises, these once useful
      skill sets need to be revisited, understood, taught, and utilized by triage
      planners, triage officers, and teams as a necessary adjunct to physiologically
      based triage decision-making. (Disaster Med Public Health Preparedness.
      2018;12:76-85).

PMID- 28427483
TI  - Do No Harm: Moving Beyond Weight Loss to Emphasize Physical Activity at Every
      Size.

PMID- 28427482
TI  - A genetic variant brain-derived neurotrophic factor (BDNF) polymorphism interacts
      with hostile parenting to predict error-related brain activity and thereby risk
      for internalizing disorders in children.
AB  - The error-related negativity (ERN) is a negative deflection in the event-related
      potential occurring when individuals make mistakes, and is increased in children
      with internalizing psychopathology. We recently found that harsh parenting
      predicts a larger ERN in children, and recent work has suggested that variation
      in the brain-derived neurotrophic factor (BDNF) gene may moderate the impact of
      early life adversity. Parents and children completed measures of parenting when
      children were 3 years old (N = 201); 3 years later, the ERN was measured and
      diagnostic interviews as well as dimensional symptom measures were completed. We
      found that harsh parenting predicted an increased ERN only among children with a
      methionine allele of the BDNF genotype, and evidence of moderated mediation: the
      ERN mediated the relationship between parenting and internalizing diagnoses and
      dimensional symptoms only if children had a methionine allele. We tested this
      model with externalizing disorders, and found that harsh parenting predicted
      externalizing outcomes, but the ERN did not mediate this association. These
      findings suggest that harsh parenting predicts both externalizing and
      internalizing outcomes in children; however, this occurs through different
      pathways that uniquely implicate error-related brain activity in the development
      of internalizing disorders.

PMID- 28427484
TI  - Racial and Ethnic Subgroup Disparities in Hypertension Prevalence, New York City
      Health and Nutrition Examination Survey, 2013-2014.
AB  - INTRODUCTION: Racial/ethnic minority adults have higher rates of hypertension
      than non-Hispanic white adults. We examined the prevalence of hypertension among
      Hispanic and Asian subgroups in New York City. METHODS: Data from the 2013-2014
      New York City Health and Nutrition Examination Survey were used to assess
      hypertension prevalence among adults (aged >=20) in New York City (n = 1,476).
      Hypertension was measured (systolic blood pressure >=140 mm Hg or diastolic blood
      pressure >=90 mm Hg or self-reported hypertension and use of blood pressure
      medication). Participants self-reported race/ethnicity and country of origin.
      Multivariable logistic regression models assessed differences in prevalence by
      race/ethnicity and sociodemographic and health-related characteristics. RESULTS:
      Overall hypertension prevalence among adults in New York City was 33.9% (43.5%
      for non-Hispanic blacks, 38.0% for Asians, 33.0% for Hispanics, and 27.5% for non
      Hispanic whites). Among Hispanic adults, prevalence was 39.4% for Dominican,
      34.2% for Puerto Rican, and 27.5% for Central/South American adults. Among Asian
      adults, prevalence was 43.0% for South Asian and 39.9% for East/Southeast Asian
      adults. Adjusting for age, sex, education, and body mass index, 2 major
      racial/ethnic minority groups had higher odds of hypertension than non-Hispanic
      whites: non-Hispanic black (AOR [adjusted odds ratio], 2.6; 95% confidence
      interval [CI], 1.7-3.9) and Asian (AOR, 2.0; 95% CI, 1.2-3.4) adults. Two
      subgroups had greater odds of hypertension than the non-Hispanic white group:
      East/Southeast Asian adults (AOR, 2.8; 95% CI, 1.6-4.9) and Dominican adults
      (AOR, 1.9; 95% CI, 1.1-3.5). CONCLUSION: Racial/ethnic minority subgroups vary in
      hypertension prevalence, suggesting the need for targeted interventions.

PMID- 28427485
TI  - Gender-specific Association of Sleep Duration with Body Mass Index, Waist
      Circumference, and Body Fat in Chinese Adults.
AB  - OBJECTIVE: To examine the association between habitual sleep duration and obesity
      among Chinese adults. METHODS: The association of sleep duration and obesity was
      investigated among 7,094 community-dwelling Chinese adults. Sleep duration was
      self-reported. In this study, obesity was defined as follows: body mass index
      (BMI) ? 28 kg/m2, waist circumference (WC) ? 85 cm in men and ? 80 cm in women,
      and percent body fat (%BF) ? 25 in men and ? 35 in women. Logistic and quantile
      regressions were employed to examine relationships of interest. RESULTS: Overall,
      6.42% of the participants reported short sleep durations (< 6 h/d) while 14.71%
      reported long (? 9 h/d) sleep durations. Long sleepers (? 9 h/d) represented a
      greater frequency of women with obesity [odds ratio (OR): 1.30; 95% confidence
      interval (CI), 1.02-1.67] and high body fat (1.43, 1.04-1.96) than those who
      slept 7-8 h/d. An association between long sleep times and higher BMI estimations
      was found across the 10th-75th percentile of the BMI distribution. Among men,
      long sleepers (? 9 h/d) presented lower risks of developing abdominal obesity
      compared with individuals who slept 7-8 h/d (OR = 0.79, 95% CI: 0.44-0.99).
      CONCLUSION: Our study suggests that long sleep durations are associated with
      general obesity in Chinese women but reduced waist circumferences in men.
      Confirmatory studies are needed to determine the heterogeneous association of
      sleep time and obesity by gender.

PMID- 28427486
TI  - Serum Gamma-glutamyl Transferase Levels Predict Functional Outcomes after
      Aneurysmal Subarachnoid Hemorrhage.
AB  - OBJECTIVE: We aim to explore the potential association between serum gamma
      glutamyl transferase levels and functional outcome after aneurysmal subarachnoid
      hemorrhage in a Chinese population. METHODS: A total of 386 aneurysmal
      subarachnoid hemorrhage patients were included in the study from September 2007
      to February 2015. Baseline serum gamma-glutamyl transferase levels and 6-month
      follow-up functional outcomes were determined. A poor outcome was defined as a
      modified ranking scale score of ? 3. The multivariable logistic model was used to
      analyze the relationship between serum gamma-glutamyl transferase and clinical
      outcomes after aneurysmal subarachnoid hemorrhage. RESULTS: The adjusted poor
      outcome rates of patients with gamma-glutamyl transferase levels of < 30 U/L, 30
      50 U/L and ? 50 U/L were 16.7%, 19.6%, and 34.4%, respectively (P < 0.01). The
      age-sex and multivariable adjusted odds ratios (95% confidence intervals) of poor
      prognosis comparing the top group (? 50 U/L) with the lowest group (< 30 U/L)
      were 5.76 (2.74-12.13), 6.64 (2.05-21.52), and 6.36 (1.92-21.02). A significant
      linear trend existed between gamma-glutamyl transferase level and aneurysmal
      subarachnoid hemorrhage prognosis. This association was also observed among
      nondrinkers. CONCLUSION: Patients with higher gamma-glutamyl transferase levels
      were more likely to have a poor prognosis. Serum gamma-glutamyl transferase can
      be considered to be an independent predictor of functional outcomes after
      aneurysmal subarachnoid hemorrhage.

PMID- 28427487
TI  - The Predictive Value of Baseline HBsAg Level and Early Response for HBsAg Loss in
      Patients with HBeAg-positive Chronic Hepatitis B during Pegylated Interferon
      Alpha-2a Treatment.
AB  - OBJECTIVE: To explore the predictive value of baseline HBsAg level and early
      response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B
      during pegylated interferon alpha-2a treatment. METHODS: A total of 121 patients
      with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled;
      all patients were treated with PEG-IFNalpha-2a 180 MUg/week. Serum HBV DNA and
      serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined
      before and every 3 months during treatment. RESULTS: The median treatment time
      for HBsAg loss was 84 weeks (7-273 weeks), and 74.38% (90 cases) of the patients
      needed extended treatment (> 48 weeks). The correlation between baseline HBsAg
      levels and the treatment time of HBsAg loss was significant (B = 14.465, t =
      2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg
      at 24 weeks significantly correlated with the treatment time of HBsAg loss (B =
      29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005). CONCLUSION:
      Baseline HBsAg levels and extended therapy are critical steps toward HBsAg loss.
      Baseline HBsAg levels together with early response determined the treatment time
      of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during
      pegylated interferon alpha-2a treatment.

PMID- 28427488
TI  - Nr2e1 Downregulation Is Involved in Excess Retinoic Acid-induced Developmental
      Abnormality in the Mouse Brain.
AB  - OBJECTIVE: This study aimed to investigate the expression pattern and function of
      Nuclear receptor subfamily 2 group E member 1 (Nr2e1) in retinoic acid (RA)
      induced brain abnormality. METHODS: The mouse model of brain abnormality was
      established by administering 28 mg/kg RA, and neural stem cells (NSCs) were
      isolated from the mouse embryo and cultured in vitro. Nr2e1 expression was
      detected by whole mount in situ hybridization, RT-PCR, and Western blotting.
      Nr2e1 function was determined by transducing Nr2e1 shRNA into NSCs, and the
      effect on the sonic hedgehog (Shh) signaling pathway was assessed in the cells.
      In addition, the regulation of Nr2e1 expression by RA was also determined in
      vitro. RESULTS: Nr2e1 expression was significantly downregulated in the brain and
      NSCs of RA-treated mouse embryos, and knockdown of Nr2e1 affected the
      proliferation of NSCs in vitro. In addition, a similar expression pattern of
      Nr2e1 and RA receptor (RAR) alpha was observed after treatment of NSCs with
      different concentrations of RA. CONCLUSION: Our study demonstrated that Nr2e1
      could be regulated by RA, which would aid a better understanding of the mechanism
      underlying RA-induced brain abnormality.

PMID- 28427489
TI  - Effects of Structural Changes in Subchondral Bone on Articular Cartilage in a
      Beagle Dog Model.
AB  - OBJECTIVE: Using MR T2-mapping and histopathologic score for articular cartilage
      to evaluate the effect of structural changes in subchondral bone on articular
      cartilage. METHODS: Twenty-four male Beagle dogs were randomly divided into a
      subchondral bone defect group (n = 12) and a bone cement group (n = 12). Models
      of subchondral bone defectin the medial tibial plateau and subchondral bone
      filled with bone cement were constructed. In all dogs, the left knee joint was
      used as the experimental sideand the right knee as the sham side. The T2 value
      for articular cartilage at the medial tibial plateau was measured at
      postoperative weeks 4, 8, 16, and 24. The articular cartilage specimens were
      stained with hematoxylin and eosin, and evaluated using the Mankin score.
      RESULTS: There was a statistically significant difference (P < 0.05) in Mankin
      score between the bone defect group and the cement group at postoperative weeks
      16 and 24. There was a statistically significant difference in the T2 values
      between the bone defect group and its sham group (P < 0.05) from week 8, and
      between the cement group and its sham group (P < 0.05) from week 16. There was
      significant difference in T2 values between the two experimental groups at
      postoperative week 24 (P < 0.01). The T2 value for articular cartilage was
      positively correlated with the Mankin score (rho = 0.758, P < 0.01). CONCLUSION:
      Structural changes in subchondral bone can lead to degeneration of the adjacent
      articular cartilage. Defects in subchondral bone cause more severe degeneration
      of cartilage than subchondral bone filled with cement. The T2 value for articular
      cartilage increases with the extent of degeneration. MR T2-mapping images and the
      T2 value for articular cartilage can indicate earlycartilage degeneration.

PMID- 28427490
TI  - Is the Mortality Trend of Ischemic Heart Disease by the GBD2013 Study in China
      Real?
AB  - To determine the reason for the different mortality trends of ischemic heart
      disease (IHD) for China between Global Burden of Disease (GBD) 2010 and GBD2013,
      and to improve garbage code (GC) redistribution. All data were obtained from the
      disease surveillance points system, and two proportions for assigning chronic
      pulmonary heart disease (PHD) as GC to IHD were from GBD2010 and GBD2013, which
      were different for years before 2004. By using the GBD2013 approach, the age
      standard mortality rate (ASMR) increased by 100.21% in 1991, 44.81% in 1996, and
      42.47% in 2000 in comparison with the GBD2010 approach. The different methods of
      chronic PHD redistribution impacted the trend of IHD mortality, which elevated it
      in the earlier 1990s by using the GBD2013 approach. Thus, improving the
      redistribution of GC as a key step in mortality statistics is important.

PMID- 28427491
TI  - Identification of a Newly Isolated Getah Virus in the China-Laos Border, China.
AB  - In this study, we isolated a virus strain (YN12031) from specimens of Armigeres
      subalbatus collected in the China-Laos border. BHK-21 cells infected with YN12031
      exhibited an evident cytopathic effect (CPE) 32 h post-infection. The virus
      particles were spherical, 70 nm in diameter, and enveloped; they also featured
      surface fibers. Molecular genetic analysis revealed that YN12031 was closely
      related to alpha viruses such as Chikungunya virus and Sindbis virus, and located
      in the same clade as MM2021, the prototype of Getahvirus (GETV) isolated in
      Malaysia in 1955. Phylogenetic analysis of the E2 and capsid genes further
      revealed that YN12031 was located in the same clade as the Russian isolate
      LEIV/16275/Mag. Analysis of the homology of nucleotides and amino acids in the
      coding area and E2 gene demonstrated that the YN12031 isolated from the China
      Laos border (tropical region) was related closest to the LEIV/16275/Mag isolate
      obtained in Russia (North frigid zone area) among other isolates studied. These
      results suggest that GETV can adapt to different geographical environments to
      propagate and evolve. Thus, strengthening the detection and monitoring of GETV
      and its related diseases is very crucial.

PMID- 28427492
TI  - Maternal Lead Exposure Induces Down-regulation of Hippocampal Insulin-degrading
      Enzyme and Nerve Growth Factor Expression in Mouse Pups.
AB  - Lead exposure is a known potential risk factor for neurodegenerative diseases
      such as Alzheimer's disease (AD). Exposure to lead during the critical phase of
      brain development has been linked with mental retardation and hypophrenia in
      later life. This study was aimed to investigate the effects of lead exposure of
      pregnant mice on the expressions of insulin-degrading enzyme (IDE) and nerve
      growth factor (NGF) in the hippocampus of their offspring. Blood samples were
      collected from the tail vein, and after anesthetizing the pups, the brain was
      excised on postnatal day 21. Lead concentrations were determined by graphite
      furnace atomic absorption spectrophotometry, and the expressions of IDE and NGF
      were determined by immunohistochemistry and Western blotting. Results showed that
      the reduction in IDE and NGF expression in the hippocampus of pups might be
      associated with impairment of learning and memory and dementia induced by
      maternal lead exposure during pregnancy and lactation.

PMID- 28427493
TI  - Hair Mercury Levels and Their Relationship with Seafood Consumption among
      Preschool Children in Shanghai.
AB  - Mercury is a global pollutant. Children are vulnerable to environmental
      toxicants. Seafood consumption is a major source of methylmercury exposure. In
      order to ascertain children's mercury exposure levels and study their
      relationship with seafood consumption, we conducted a cross-sectional study among
      preschool children in Shanghai. According to our data, the geometric mean of the
      mercury levels in children's hair was 191.9 (95% CI: 181.8, 202.4) MUg/kg. These
      results indicate that high income may be a predictor of elevated mercury levels
      in children's hair. Intake of marine fish, especially tuna and pomfret, was
      documented in our study and found to increase the risk of high mercury levels.
      Frequency of fish consumption was positively related with hair mercury levels.
      Our study is the first to provide baseline data for hair mercury concentration
      among preschool children in Shanghai.

PMID- 28427494
TI  - Characterization and Expression Analysis of Peroxiredoxin Genes in NNK-induced
      V79 Cells.
AB  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent and prevalent
      nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to
      study alterations in peroxiredoxin (Prx) expression induced by NNK during
      carcinogenesis. Characterization of Prx genes from hamster was performed using
      bioinformatics. V79 cells were induced with different concentrations of NNK (0.1
      0.4 mg/mL), and the expression levels of six Prx genes (Prx1-Prx6) were measured
      by qRT-PCR 24 h following NNK treatment. Prx gene expression was induced by NNK
      stress, and the highest transcription levels were induced by over 20.42-fold
      relative to that of the control. NNK induced alterations in Prx expression over
      the course of lung cancer, which means Prxs may play important roles in ROS
      detoxification under NNK stress and their functions are complementary.

PMID- 28427495
TI  - Sexual Dysfunction among Chinese Nurses: Prevalence and Predictors.
AB  - This study aimed to estimate the prevalence of and identify the factors
      influencing female sexual dysfunction (FSD) among Chinese nurses. A cross
      sectional survey was conducted from March 2013 to May 2014 among 6 hospitals in
      Suzhou, China. In total, 2,030 married female nurses were included in the
      analysis. Data on the sociodemographic, lifestyle, and self-reported health
      status of the participants were collected, and the participants were asked to
      complete the Chinese version of the 19-item Female Sexual Function Index (FSFI)
      questionnaire. In total, 1,035 (50.99%) participants were found to have FSD.
      Logistic regression analysis showed that increasing age and higher body mass
      index, lower salary, and poor/very poor self-reported health status were risk
      factors for FSD; however, regular social activity and physical exercise were
      protective factors for FSD. The findings of this study suggest that further
      interventional studies are warranted to study the sexual health among Chinese
      nurses in detail.

PMID- 28427496
TI  - Mortality risk factors in intensive care unit patients with acute kidney injury
      requiring renal replacement therapy: a retrospective cohort study?.
AB  - BACKGROUND: Mortality of critically-ill patients with acute kidney injury (AKI)
      requiring renal replacement therapy (RRT) in an intensive-care setting continues
      to remain high. There is still uncertainty as to which factors should guide
      clinical judgement. METHODS: A cohort of 155 patients admitted to an intensive
      care unit and necessitating RRT due to AKI were retrospectively analyzed.
      Demographic and clinical parameters at the time of RRT initiation were retrieved.
      Multi- and univariate analyses were performed to determine the impact of
      different risk factors on mortality. RESULTS: The most common causes of AKI were
      sepsis (39.3%) and cardiac events (32%). The majority of patients were treated by
      continuous (67.3%), the others by intermittent RRT. After 30 days, 51.0% of
      patients survived. Nonsurvivors were older (73 vs. 69 years), had a higher
      APACHEE II score (30.1 +/- 5.6 vs. 26.5 +/- 7.1), and were more likely to be
      vasopressor dependent, mechanically ventilated, or treated by continuous RRT.
      Multivariate analysis revealed that higher age, higher APACHEE II score, and
      lower serum creatinine at baseline were independent predictors for mortality,
      whereas histories of diabetes mellitus, arterial hypertension, coronary heart
      disease, or stroke were not. CONCLUSION: Critically-ill patients with AKI
      requiring RRT continue to have a high mortality. Age and APACHE II score showed
      an impact on mortality whereas traditional cardiovascular risk factors did not.
      Higher BUN and creatinine levels do not have a negative impact on mortality. Our
      findings support the current practice that RRT initiation should primarily be
      guided by clinical decision.?.

PMID- 28427497
TI  - Mirtazapine-induced steatosis?.
AB  - Mirtazapine is a commonly used drug indicated for the treatment of severe
      depression. It works as a presynaptic alpha<sub>2</sub>-adrenoreceptor antagonist
      that increases central noradrenergic and serotonergic neurotransmission, and it
      is metabolized by the p450 cytochrome oxidase system. There is evidence within
      the literature to suggest a link between antidepressants and increased liver
      enzymes, although case reports demonstrating a link between mirtazapine
      specifically and steatosis are sparse. Here, we present a case of mirtazapine
      induced steatosis in a 48-year-old office worker. She presented with painless
      jaundice of 2 days duration and generalized lethargy and peripheral edema present
      for 3 weeks beforehand. Extensive investigations were undertaken to identify the
      cause of her jaundice but no biochemical, blood-borne, or anatomical cause could
      be found. Mirtazapine was subsequently stopped, and her liver function, both
      clinically and biochemically, improved rapidly. She made a full recovery after
      discontinuation of her mirtazapine.?.

PMID- 28427499
TI  - Coexistent venous angioma and focal cortical dysplasia.

PMID- 28427498
TI  - Plasma and saliva concentrations of abacavir, tenofovir, darunavir, and
      raltegravir in HIV-1-infected patients?.
AB  - OBJECTIVE: We studied the relationships between plasma and saliva concentrations
      of antiretroviral drugs to explore whether saliva can be used for therapeutic
      drug monitoring (TDM). METHODS: Abacavir (ABC), tenofovir (TFV), darunavir (DRV),
      and raltegravir (RAL) in plasma and saliva from 30 HIV-1-infected patients were
      quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Mean
      saliva-to-plasma concentration ratios were 0.623 (ABC), 0.024 (TFV), 0.065 (DRV),
      and 0.0135 (RAL), which agree with the plasma protein binding rates except TFV.
      Significant correlations were evident between saliva and plasma concentrations of
      ABC, DRV, and RAL. CONCLUSIONS: This study suggests that plasma concentrations of
      ABC, DRV, and RAL can be estimated from their saliva concentrations and that the
      saliva concentration of some antiretroviral drugs reflects the unbound drug
      concentration in plasma.?.

PMID- 28427500
TI  - Specificity protein 1: Its role in colorectal cancer progression and metastasis.
AB  - Specificity protein 1 (Sp1) is a widely expressed transcription factor that plays
      an important role in the promotion of oncogenes required for tumor survival,
      progression and metastasis. Sp1 is highly expressed in several cancers including
      colorectal cancer (CRC) and is related to poor prognosis. Therefore, targeting
      Sp1 is a rational for CRC therapy. In this review, we will recapitulate the
      current understanding of Sp1 signaling, its molecular mechanisms, and its
      potential involvement in CRC growth, progression and metastasis. We will also
      discuss the current therapeutic drugs for CRC and their mechanism of action via
      Sp1.

PMID- 28427501
TI  - The cancer stem cell phenotype as a determinant factor of the heterotypic nature
      of breast tumors.
AB  - Gathering evidence supports the existence of a population of cells with stem-like
      characteristics, named cancer stem cells (CSC), which is involved not only in
      tumor recurrence but also in tumorigenicity, metastization and drug resistance.
      Several markers have been used to identify putative CSC sub-populations in
      different cancers. Notwithstanding, it has been acknowledged that breast CSC may
      originate from non-stem cancer cells (non-SCC), interconverting through an
      epithelial-to-mesenchymal transition-mediated process, and presenting several
      deregulated canonical and developmental signaling pathways. These support the
      heterogeneity that, directly or indirectly, influences fundamental biological
      features supporting breast tumor development. Accordingly, CSC have increasingly
      become highly relevant cellular targets. In this review, we will address the
      stemness concept in cancer, setting the perspective on CSC and their origin, by
      exploring their relation and regulation within the tumor microenvironment, in the
      context of emerging therapeutic targets. Within this framework, we will discuss
      nucleolin, a protein that has been associated with angiogenesis and, more
      recently, with the stemness phenotype, becoming a common denominator between CSC
      and non-SCC for multicellular targeting.

PMID- 28427502
TI  - Radiosurgery for intracranial meningiomas: A systematic review and meta-analysis.
AB  - BACKGROUND: Radiosurgery(RS), both in single and multiple sessions, have been
      performed for intracranial meningiomas. Different aspects are still controversial
      on this field. The aim of this systematic review is to summarize the current
      literature on long-term efficacy and safety of RS for meningiomas. METHODS:
      Online databases were searched for studies published until April 2015. The
      primary outcomes were disease control and progression-free-survival(PFS). The
      secondary outcomes were symptom control and radiation-induced toxicity. RESULTS:
      The estimate of disease control rate ranged from 87.0% to 100.0% at 5 years and
      from 67.0% to 100.0% at 10 years. The PFS rate ranged 78.0%-98.9% and 53.1%-97.2%
      at 5 and 10 years, respectively. The overall symptom control was 92.3%, the
      overall toxicity was 8.1%. CONCLUSIONS: RS can be considered a safe and effective
      treatment. Efforts are needed in standardizing the definition of local and
      symptom control and toxicity in order to properly compare different treatment
      schedules.

PMID- 28427503
TI  - Oesophageal cancer: Which treatment is the easiest to swallow? A review of
      combined modality treatments for resectable carcinomas.
AB  - Oesophageal cancer is a relatively uncommon malignancy, but with poor prognosis.
      Despite several treatment options that are available, the 5-year survival rates
      rarely exceed 40%. This review discusses the main challenges of oesophageal
      cancer, the available treatment options, and the most effective treatment in
      terms of overall survival. The outcomes of clinical trials show that neo-adjuvant
      chemo-radiotherapy using cisplatin and 5-fluorouracil followed by oesophagectomy
      results in the greatest survival. However, the optimal chemotherapy and
      radiotherapy schedule remains unclear. There is no satisfactory treatment to
      date, particularly for patients with co-morbidities or advanced tumours.

PMID- 28427504
TI  - Follow-up program in head and neck cancer.
AB  - Follow-up program in head and neck cancer (HNC) is an important issue in patients
      management. It represents the major dilemma in daily practice clinic. Many
      guidelines have been published in order to better define the best clinical
      protocol, but a consensus has not been attained yet. We constructed a follow-up
      program based on specific primary subsite, to standardize patients surveillance
      after treatment of HNC.

PMID- 28427505
TI  - Toxicity of iron overload and iron overload reduction in the setting of
      hematopoietic stem cell transplantation for hematologic malignancies.
AB  - Iron is an essential element for key cellular metabolic processes. However,
      transfusional iron overload (IOL) may result in significant cellular toxicity.
      IOL occurs in transfusion dependent hematologic malignancies (HM), may lead to
      pathological clinical outcomes, and IOL reduction may improve outcomes. In
      hematopoietic stem cell transplantation (SCT) for HM, IOL may have clinical
      importance; endpoints examined regarding an impact of IOL and IOL reduction
      include transplant-related mortality, organ function, infection, relapse risk,
      and survival. Here we review the clinical consequences of IOL and effects of IOL
      reduction before, during and following SCT for HM. IOL pathophysiology is
      discussed as well as available tests for IOL quantification including transfusion
      history, serum ferritin level, transferrin saturation, hepcidin, labile plasma
      iron and other parameters of iron-catalyzed oxygen free radicals, and organ IOL
      by imaging. Data-based recommendations for IOL measurement, monitoring and
      reduction before, during and following SCT for HM are made.

PMID- 28427506
TI  - Recent advances in genitourinary tumors: A review focused on biology and systemic
      treatment.
AB  - Updated information published up to 2016 regarding major advances in renal
      cancer, bladder cancer, and prostate cancer is here presented. Based on an ever
      better understanding of the genetic and molecular alterations that govern the
      initial pathogenic mechanisms of tumor oncogenesis, an improvement in the
      characterization and treatment of urologic tumors has been achieved in the past
      year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the
      MET pathway are characteristics of type 1 papillary renal cell carcinomas, and
      activation of NRF2-ARE pathway is associated with the biologically distinct type
      2. While sunitinib and pazopanib continue to be the standard first-line treatment
      in metastatic renal cell carcinoma of clear cell histology, nivolumab and
      cabozantinib are now the agents of choice in the second-line setting. In relation
      to urothelial bladder carcinoma, new potential molecular targets such as FGFR3,
      PI3K/AKT, RTK/RAS, CDKN2A, ARIDIA, ERBB2 have been identified. Response to
      adjuvant cisplatin-based chemotherapy appears to be related to basal, luminal,
      and p53-like intrinsic subtypes. A phase II study with eribulin and a maintenance
      phase II trial with vinflunine have shown promising results. Similarly, the use
      of the check point inhibitors in advanced disease is likely to revolutionize the
      management of patients who have progressed after cisplatin-based chemotherapy. In
      prostate cancer, seven mutually exclusive molecular subtypes have been identified
      by the TCGA project. Chemotherapy has been consolidated as a key treatment for
      castration-sensitive metastatic prostate cancer, and abiraterone, enzalutamide,
      cabazitaxel, and radium-223 remain standard therapeutic options for men with
      metastatic castration-resistant prostate cancer. All this progress will
      undoubtedly contribute to the development of new treatments and therapeutic
      strategies that will improve the survival and quality of life of our patients.

PMID- 28427507
TI  - Is still there a place for orteronel in management of prostate cancer? Data from
      a literature based meta-analysis of randomized trials.
AB  - Orteronel (TAK-700) is an oral, non-steroidal 17,20-lyase inhibitor with higher
      specificity for 17,20 lyase over 17 hydroxylase. The first phase III studies
      showed an advantage with orteronel compared with placebo in terms of progression
      free survival and response of PSA. Unfortunately orteronel did not significantly
      prolong the overall survival. In order to assess the efficacy of orteronel in
      prostate cancer, we evaluated all available data on orteronel in the management
      of prostate cancer. A total of 2716 patients were evaluated from 3 randomized
      trials. We showed orteronel improved the progression free survival, time to PSA
      progression and PSA response compared with the placebo. In conclusion, given the
      limitations a literature rather than on individual patients' data meta-analysis,
      our data show a clinical efficacy of orteronel in prostate cancer, therefore we
      deem that orteronel may be investigated in combination with the other approved
      agents for CRPC or be tested in prior setting of disease such as the hormone
      sensitive prostate cancer.

PMID- 28427508
TI  - Review of current evidence available for guiding optimal Enoxaparin prophylactic
      dosing strategies in obese patients-Actual Weight-based vs Fixed.
AB  - BACKGROUND: The current debate over the optimal Enoxaparin prophylactic dosing
      strategies in obese patients centre around whether it should be based on the
      actual weight of the patient (i.e. weight-based), or at an artificially fixed
      amount, as it is the case in Australia (40mg daily). The vast majority of the
      evidence available today is laboratory-based, measuring serum Antifactor-Xa
      activities as a marker for physiological response. AIM: The aim of the parent
      study is to compare the clinical outcomes for obese patients who received fixed
      doses of enoxaparin compared to those who received weight-based doses within the
      licensed dosage recommendations. This review was conducted to examine whether a
      gap in knowledge exists in relation to dosing obese patients with enoxaparin as
      VTE prophylaxis after hospital admission to aid in development of the parent
      study concept. METHOD: Databases such as Medline, EBSCOhost, ProQuest were
      interrogated using combinations of words such as "enoxaparin", AND "dosing
      strategy", AND "obese/obesity" AND "prophylaxis". Only eleven out of 14 primary
      studies which were considered to be sufficiently similar in methodology and
      anticipated outcomes were reviewed and analysed. RESULTS: Pooled data from the
      eleven studies suggested that weight-based or higher-than-fixed dosing had a
      36.2% higher success rate than fixed dosing, and was more likely to achieve the
      desired serum Anti-Xa activity levels (52.2% and 16% respectively). The rate of
      failure to achieve this is significantly lower in the weight-based groups (13.3%)
      than in fixed-dose groups (18.5%). These eleven studies reviewed included 601
      patients in total. CONCLUSION: There is insufficient evidence to support or
      negate the current enoxaparin health outcomes in obese and very obese patients
      due to the lack of post-discharge follow-up from hospitals. Further research is
      required to compare long-term outcomes after fixed and weight-based dosing of
      enoxaparin. The optimal dose of enoxaparin per kilogram of body weight for
      prophylaxis remains to be determined.

PMID- 28427509
TI  - Efficacy and safety of bortezomib, thalidomide, and lenalidomide in multiple
      myeloma: An overview of systematic reviews with meta-analyses.
AB  - This overview summarizes evidence for the efficacy and safety of bortezomib,
      thalidomide, and lenalidomide in patients with multiple myeloma. We searched the
      Medline, Scopus, and LILACS databases through August 2016, including systematic
      reviews with meta-analyses of randomized controlled trials assessing the efficacy
      and/or safety of bortezomib, thalidomide, or lenalidomide in patients with
      multiple myeloma. Two authors performed study selection, data extraction, and
      quality assessment using AMSTAR and GRADE instruments. Twenty-nine studies
      satisfied the inclusion criteria. All three drugs significantly improved overall
      response and progression-free survival; however, only bortezomib showed
      significantly greater overall survival compared with the control arm (induction
      therapy, continuous therapy, or at any phase of treatment). The main concerns on
      adverse events were thrombosis/embolism events, peripheral neuropathy, and second
      primary malignancies. The most common problems detected in systematic reviews
      were non-registration of the study protocol and conflicts of interest not clearly
      acknowledged. Future research should adhere to quality assessment tools so that
      best evidence can be used in decision-making. Protocol PROSPERO registration
      number: CRD42016036062.

PMID- 28427510
TI  - Central nervous system gliomas.
AB  - Evidence-based practical guidelines on diagnosis, prognosis, and treatment on the
      most frequent adult brain tumours are delineated. In Europe, 27,000 new cases of
      malignant glial tumours and 1000 new cases of malignant ependymal tumours are
      diagnosed every year. The most common glial tumours are glioblastoma multiforme
      and anaplastic glioma, comprising more than 50% and 10%, respectively, of the
      total gliomas. Prognosis of gliomas is generally poor. Environmental and genetic
      factors have been correlated with an increased risk of developing brain tumours.
      Surgical resection represents the first treatment option for all histotypes. Role
      and timing of radiotherapy and chemotherapy as well as treatment for
      recurrent/progressive disease should be based on age, performance status,
      histopathological diagnosis, molecular markers, and previous therapy. Impaired
      neurocognitive and neuropsychological function is common in long-term survivors,
      regardless of the histology and grade of the tumour and should be taken into
      account in treatment planning.

PMID- 28427511
TI  - Role of hypoxia-inducible factors (HIF) in the maintenance of stemness and
      malignancy of colorectal cancer.
AB  - Hypoxia is a condition of insufficient tissue oxygenation, which is observed
      during normal development as well as tumorigenesis and its response at the
      cellular level is primarily mediated through hypoxia inducible factors (HIFs).
      HIFs have a significant role in the maintenance of stemness in both stem cells as
      well as in cancer stem cells (CSC) by acting as transcription factors. The CSCs
      are proposed to be the driving force of colon tumorigenesis and malignancy. These
      HIFs play a significant role in a wide range of diseases including colon cancer.
      HIF's signaling functions with stemness, and maintaining Wnt/beta-catenin
      signaling pathways. Due to HIFs functional significance in stemness maintenance
      in malignancy, targeting HIFs might provide a new approach for development of new
      therapy for colon cancer. In this review, we will be briefing on the colon and
      its stem cells, various molecular signaling pathways involved in stemness
      preservation, and the role hypoxia and its HIFs in the maintenance of stemness in
      colon stem cells and colon cancer stem cells.

PMID- 28427512
TI  - Impact of hyperglycemia on the efficacy of chemotherapy-A systematic review of
      preclinical studies.
AB  - BACKGROUND: Antineoplastic agents can provoke hyperglycemia in cancer patients
      with and without diabetes mellitus. We systematically reviewed the impact of
      hyperglycemia on the efficacy of chemotherapy. METHODS: MEDLINE was searched for
      preclinical intervention studies which compared chemotherapy response in
      hyperglycemic and euglycemic conditions. RESULTS: Thirteen preclinical studies,
      including 23 cell lines and 2 animal experiments were identified. In 14 cell
      lines and 2 animal studies, chemotherapy response was lower in a hyperglycemic
      (>15mmol/L) compared to a euglycemic environment (5mmol/L). The response was
      similar in 4 cell lines. In the remaining 5 cell lines, the hyperglycemic
      environment potentiated chemotherapy efficacy. CONCLUSION: Hyperglycemia
      attenuated the antiproliferative effect of chemotherapy in preclinical
      experiments, but the results are inconsistent. Whether hyperglycemia influences
      efficacy of chemotherapy in patients needs to be explored.

PMID- 28427513
TI  - Polymerase proofreading domain mutations: New opportunities for immunotherapy in
      hypermutated colorectal cancer beyond MMR deficiency.
AB  - Immune checkpoint inhibition is a new therapeutic strategy that has shown
      promising efficacy in many cancer types. Significant activity associated with
      mismatch repair (MMR) deficiency has been observed in hypermutated,
      microsatellite unstable (MSI) metastatic colorectal cancer (CRC). Beyond
      deficient-MMR tumors, somatic or germline DNA polymerase D1 (POLD1) or DNA
      polymerase E (POLE) alterations cause a hypermutated phenotype in CRC. This
      recently identified and rare subgroup of proficient-MMR tumors may also benefit
      from immunotherapy. In this review, we provide a comprehensive overview of recent
      data on CRC tumors harboring POLD1 or POLE mutations, with a focus on their
      molecular, histological, and clinical features. We also examine the evidence
      supporting the development of immune checkpoint inhibitors in this specific
      subgroup of CRC patients.

PMID- 28427514
TI  - Triplet versus doublet combination regimens for the treatment of relapsed or
      refractory multiple myeloma: A meta-analysis of phase III randomized controlled
      trials.
AB  - During the past decades, several prospective trials had been conducted to assess
      the efficacy and toxicities of triplet versus doublet combination regimens for
      the treatment of relapsed or refractory multiple myeloma (RRMM), but the results
      were controversial. We thus performed a systematic literature search to identify
      relevant trials. Summary hazard ratios (HRs), relative risks (RRs), and 95%
      confidence intervals (95%CIs) were calculated. A total of 3197 RRMM patients were
      included for analysis. The pooled results demonstrated that triplet combination
      therapies significantly improve OS (HR 0.83, 95%CI: 0.71-0.94, p=0.004) and PFS
      (HR 0.68, 95%CI: 0.62-0.74, p<0.001). The pooled RRs of ORR, very good partial
      response (VGPR) and complete response (CR) with triplets vs. doublets were 1.19
      (95%CI: 1.10-1.27), 1.44 (95%CI: 1.18-1.77), and 1.76 (95%CI: 1.04-2.97),
      respectively, indicating that the RRs of achieving deeper responses were higher
      with triplets, though the RRs of overall>=grade 3 adverse events (RR 1.11,
      p=0.001) and >=grade 3 thrombocytopenia (RR 1.64, p=0.009) was higher with
      triplets. In conclusion, our meta-analysis demonstrated that triplet regimens
      result in improved OS, PFS, ORR, VGPR, and CR when compared to doublets, though
      the risk of grade 3 and 4 adverse events were higher with triplets.

PMID- 28427515
TI  - FGFR a promising druggable target in cancer: Molecular biology and new drugs.
AB  - INTRODUCTION: The Fibroblast Growth Factor Receptor (FGFR) family consists of
      Tyrosine Kinase Receptors (TKR) involved in several biological functions.
      Recently, alterations of FGFR have been reported to be important for progression
      and development of several cancers. In this setting, different studies are trying
      to evaluate the efficacy of different therapies targeting FGFR. AREAS COVERED:
      This review summarizes the current status of treatments targeting FGFR, focusing
      on the trials that are evaluating the FGFR profile as inclusion criteria: Multi
      Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR
      Monoclonal Antibodies. EXPERT OPINION: Most of the TKR share intracellular
      signaling pathways; therefore, cancer cells tend to overcome the inhibition of
      one tyrosine kinase receptor by activating another. The future of TKI (Tyrosine
      Kinase Inhibitor) therapy will potentially come from multi-targeted TKIs that
      target different TKR simultaneously. It is crucial to understand the interaction
      of the FGF-FGFR axis with other known driver TKRs. Based on this, it is possible
      to develop therapeutic strategies targeting multiple connected TKRs at once. One
      correct step in this direction is the reassessment of multi target inhibitors
      considering the FGFR status of the tumor. Another opportunity arises from
      assessing the use of FGFR TKI on patients harboring FGFR alterations.

PMID- 28427516
TI  - Prognostic and predictive biomarkers in neuroendocrine tumours.
AB  - Neuroendocrine tumours are extremely heterogeneous malignancies. Despite marked
      heterogeneity in clinical course and prognosis, few biomarkers exist to help
      predict prognosis and guide treatment. Many tumour-based biomarkers (Ki-67,
      mitotic count, genetic/epigenetic changes and microRNAs) exist, but only Ki-67
      and mitotic count have strong evidence to support their routine use. Blood-based
      markers are easily repeatable, but currently established biomarkers (chromogranin
      A and urinary 5-HIAA) are difficult to measure accurately in practice. Structural
      imaging is used routinely via the TNM system. Functional imaging such as 68Ga
      based and FDG PET may become valuable biomarkers with their increasing
      availability, aided by ongoing quantitative research. Multiple nomograms have
      been proposed to integrate the above factors, but most have not been
      prospectively validated and are difficult to use in practice. Further research
      should aim to establish robust new biomarkers and integrate existing ones to help
      optimise NET treatment.

PMID- 28427517
TI  - Interim 18FDG PET/CT during radiochemotherapy in the management of pelvic
      malignancies: A systematic review.
AB  - 18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT) is widely applied in oncology for
      disease staging, assessment of therapy response, relapse diagnosis, follow-up and
      target volume delineation. In particular, it can detect early response during
      chemoradiotherapy (interim) because functional modifications usually precede
      morphological ones. This ability is crucial to the radiation oncologist for the
      management of patients, to avoid persisting with ineffective therapy - often
      leading toxicity - and to shift to potentially more effective alternatives.
      Interim 18F FDG-PET imaging in rectal and cervical cancer, the main malignancies
      of the pelvic district, has been applied and a broad literature is available,
      although some results are discordant. This systematic review summarizes the
      application of 18F FDG-PET/CT during the chemoradiotherapy of locally advanced
      pelvic malignancies in order to clarify its capability to predict response and
      prognosis and its potential role to tailor therapy, which seems to be validated
      in rectal cancer, whilst less conclusive in cervical cancer.

PMID- 28427518
TI  - Controversies in clinicopathological characteristics and treatment strategies of
      male breast cancer: A review of the literature.
AB  - Male breast cancer (MaBC) is a rare disease, accounting for less than 1% of
      malignancies in men. For this reason, literature data on its clinicopathological
      characteristics are very heterogeneous and treatment strategies have mostly been
      extrapolated from the female counterpart. However, immunohistochemical
      peculiarities of MaBC have recently emerged, defining it as a distinct entity
      from female breast cancer (FBC), thus requiring a tailored clinical approach.
      MaBC appears to be more often hormone receptor positive than FBC, while data on
      HER2 status still remain inconclusive, indicating a possible higher incidence of
      HER2 alterations. Treatment strategies for MaBC have evolved and less invasive
      local treatments such as lumpectomy and sentinel lymph node biopsy have become
      part of everyday clinical practice, while there are still controversies on the
      indication of radiotherapy, especially after mastectomy. Similarly, differences
      between male and female hormonal status have raised some concerns in the use of
      aromatase inhibitors in male patients and the choice of best endocrine therapy is
      still controversial.

PMID- 28427519
TI  - A comprehensive review of immunotherapies in prostate cancer.
AB  - Prostate cancer is the second most common malignant neoplasm in men worldwide and
      the fifth cause of cancer-related death. Although multiple new agents have been
      approved for metastatic castration resistant prostate cancer over the last
      decade, it is still an incurable disease. New strategies to improve cancer
      control are needed and agents targeting the immune system have shown encouraging
      results in many tumor types. Despite being attractive for immunotherapies due to
      the expression of various tumor associated antigens, the microenvironment in
      prostate cancer is relatively immunosuppressive and may be responsible for the
      failures of various agents targeting the immune system in this disease. To date,
      sipuleucel-T is the only immunotherapy that has shown significant clinical
      efficacy in this setting, although the high cost and potential trial flaws have
      precluded its widespread incorporation into clinical practice. Issues with
      patient selection and trial design may have contributed to the multiple failures
      of immunotherapy in prostate cancer and provides an opportunity to tailor future
      studies to evaluate these agents more accurately. We have reviewed all the
      completed immune therapy trials in prostate cancer and highlight important
      considerations for the next generation of clinical trials.

PMID- 28427520
TI  - Lymphoblastic lymphoma.
AB  - Lymphoblastic lymphoma (LBL) is a neoplasm of immature B cells committed to the B
      (B-LBL) or T-cell lineage (T-LBL) that accounts for approximately 2% of all
      lymphomas. Although histological features are usually sufficient to distinguish
      lymphoblastic from mature B- or T-cell neoplasms, of greater importance for
      diagnosis is the characterization of immunophenotype by flow cytometry. LBL
      occurs more commonly in children than in adults, mostly in males. A bone marrow
      involvement <25% (or 20% according to WHO) formally distinguishes LBL from ALL.
      The prognosis of LBL has dramatically improved with the use of intensive ALL-type
      chemotherapy regimens, which includes intensive intrathecal chemotherapy
      prophylaxis and consolidation with mediastinal irradiation. Patients with adverse
      prognostic features assessed by postinduction CT/positron emission tomography
      scans (PET) and minimal residual disease analysis (MRD) should be considered for
      high-dose chemotherapy and stem cell transplantation. Further therapeutic
      progresses are expected from the introduction of new drugs and targeting agents.

PMID- 28427521
TI  - Management of metastatic castration-resistant prostate cancer: A focus on radium
      223: Opinions and suggestions from an expert multidisciplinary panel.
AB  - Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets
      bone metastases with alpha particles, is approved for the treatment of men with
      metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone
      metastases. In patients with mCRPC, treatment with radium-223 has been associated
      with survival benefit, regardless of prior docetaxel use, and also has a positive
      impact on symptomatic skeletal events and quality of life. Radium-223 is best
      suited for patients with symptomatic mCRPC and bone-predominant disease and no
      visceral metastases, and may lead to better outcomes when given early in the
      course of the disease. An expert multidisciplinary panel convened in Milan, Italy
      to review the current best-evidence literature on radium-223 and to convey their
      personal expertise with the use of radium-223 and identify possible strategies
      for best practice. This article summarizes the best available evidence for the
      use of radium-223, discusses the essential role of the multidisciplinary team in
      delivering effective treatment for mCRPC, clarifies pre- and post-treatment
      evaluation and monitoring, and outlines future scenarios for radium-223 in the
      treatment of men with MCRPC.

PMID- 28427522
TI  - The role of anti-PD-1 and anti-PD-L1 agents in the treatment of diffuse large B
      cell lymphoma: The future is now.
AB  - Immune checkpoints inhibitors have been incorporated into standard treatment
      protocols for advanced solid tumors. The aim of T-cell-based immune therapy in
      cancer has been to generate durable clinical benefits for patients, paired with
      enhanced side effect profiles. The beneficial antitumoral activity of programmed
      death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has been thoroughly
      demonstrated in certain metastatic malignancies (e.g. melanoma, non-small cell
      lung cancer, renal cell carcinoma); however, the therapeutic role in lymphoid
      cancers is complex. Nonetheless, the striking clinical activity seen in early
      clinical trials of various subtypes of relapsed lymphoma have paved the way for
      these exciting innovative therapeutic alternatives in these tumors. In this
      article we assess the literature on the role of the PD-1/PD-L1 pathway in Diffuse
      Large B-cell lymphoma (DLBCL), and describe future strategies involving these new
      anticancer agents in this lymphoid neoplasm.

PMID- 28427523
TI  - Combination of immune checkpoint inhibitors and radiotherapy: Review of the
      literature.
AB  - Literature experiences in cancer treatment usually deal with either targeting the
      tumour cell or the immune system, which often fail to reach the curative purposes
      in many solid tumours. On the other hand, one mechanism of radiation-induced
      tumour control is the activation of the adaptive immune system by tumour antigen
      release following radiotherapy. So, combining radiation therapy with immune
      checkpoint blockade treatment at the same time may represent a way to stimulate
      the adaptive immune system, with further amplification of immune responses
      reached through systemic immune checkpoint blockade. Until now, only few studies
      deal with the association of immune checkpoint blockade treatment and
      radiotherapy. In this review, we evaluate this association, highlighting this
      possibility as a new strategy to improve outcome in cancer patients.

PMID- 28427525
TI  - Precision medicine for early breast cancer radiotherapy: Opening up new horizons?
AB  - So far most efforts put forth to test the value of predictive and prognostic
      tools in the field of breast radiotherapy remained globally disappointing, or at
      least below the convincing levels reached for systemic therapy. Nevertheless the
      addition of predictive tools to the clinical armament tends to prevail over the
      use of the sole prognostic factors, also in radiotherapy. A number of predictive
      assays, clinically validated or not, have recently elicited significant
      associations between molecular profiles and tumor biological aggressiveness
      and/or radiosensitivity levels. Will it take a long time for these radiation
      specific assays to provide added value to the - already crowded - constellation
      of predictive tools in the breast cancer? On the one hand, optimizing
      radiotherapy through the integration of precision medicine into the breast cancer
      management still remains a challenging issue. On the other hand, recent advances
      in predictive assays aimed at distinguishing patients with a more radioresistant
      tumor that necessitates radiation dose escalation or a switch to therapeutic
      approaches other than radiotherapy, plea in favor of an increasing role, in a
      near future, for radiation-specific molecular signatures. Streamlining predictive
      assays platforms via concerted actions should imperatively be given high
      priority, also in terms of health economics.

PMID- 28427526
TI  - Potential application and prevalence of the CD30 (Ki-1) antigen among solid
      tumors: A focus review of the literature.
AB  - BACKGROUND: CD30 (Ki-1) is a cell membrane protein derived from the tumor
      necrosis factor (TNF) receptor family. The CD30 antigen has been associated
      primarily with Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma
      (sALCL). Brentuximab vedotin (BV) is an antibody-drug conjugate targeting the
      CD30 antigen. FDA approval for BV includes relapsed and refractory HL and sALCL.
      The CD30 antigen also has been identified in many solid tumors, predominantly of
      germ cell origins and early clinical data is promising. OBJECTIVE: Perform a
      focus literature review evaluating the prevalence of the CD30 antigen among
      nonlymphomatous tumors with a potential correlate for CD30 targeted therapy.
      ELIGIBILITY CRITERIA: Inclusion criteria: all retrospective reviews and case
      reports citing CD30 positivity or negativity in non-lymphomatous malignancies in
      which data were presented based on location. EXCLUSION CRITERIA: studies with
      hematopoetic malignancies, cutaneous malignancies, non-human populations, and non
      english publications. INCLUDED STUDIES: A total of 119 articles met these
      criteria and are summarized in this manuscript. CONCLUSION: The CD30 antigen has
      shown variable prevalence among non-hematopoetic tumors, most notably among germ
      cell tumors and mesothelioma. With additional, preclinical and properly powered
      clinical studies, CD30 targeted therapy such as that of BV, alone or in
      combination with other agents may prove to be a strong candidate in the treatment
      of various CD30+ malignancies.

PMID- 28427524
TI  - Kallistatin suppresses cancer development by multi-factorial actions.
AB  - Kallistatin was first identified in human plasma as a tissue kallikrein-binding
      protein and a serine proteinase inhibitor. Kallistatin via its two structural
      elements regulates differential signaling cascades, and thus a wide spectrum of
      biological functions. Kallistatin's active site is essential for: inhibiting
      tissue kallikrein's activity; stimulating endothelial nitric oxide synthase and
      sirtuin 1 expression and activation; and modulating the synthesis of the
      microRNAs, miR-34a, miR-21 and miR-203. Kallistatin's heparin-binding site is
      crucial for antagonizing the signaling pathways of vascular endothelial growth
      factor, tumor necrosis factor-alpha, Wnt, transforming growth factor-beta and
      epidermal growth factor. Circulating kallistatin levels are markedly reduced in
      patients with prostate and colon cancer. Kallistatin administration attenuates
      angiogenesis, inflammation, tumor growth and invasion in animal models and
      cultured cells. Therefore, tumor progression may be substantially suppressed by
      kallistatin's pleiotropic activities. In this review, we will discuss the role
      and mechanisms of kallistatin in the regulation of cancer development.

PMID- 28427527
TI  - Venous thromboembolism in radiation therapy cancer patients: Findings from the
      RIETE registry.
AB  - BACKGROUND: Cancer patients are at high risk of venous thromboembolism,
      particularly during cancer treatment. Conversely to chemotherapy, data on the
      epidemiology and clinical features of venous thromboembolism during radiation
      therapy are scarce. There is lack of evidence on the influence of radiation
      therapy (RT) on outcome in cancer patients with acute venous thromboembolism
      (VTE). METHODS: We used the RIETE (Registro Informatizado de Enfermedad
      ThromboEmbolica) database to assess the clinical characteristics and outcome of
      prospectively-collected consecutive patients with cancer-associated thrombosis
      occurred during the course of radiation therapy for cancer. Death, venous
      thromboembolism recurrences and major bleeding rates during long-term follow-up
      according to cancer site and treatment were compared RESULTS: 9284 Patients with
      active cancer and VTE were enrolled in RIETE: 4605 with pulmonary embolism (PE)
      and 4679 with deep vein thrombosis (DVT). In all, 1202 (13%) were receiving RT.
      This last sub-population had a higher rate of PE recurrences and a similar rate
      of DVT recurrences or major bleeding than those not receiving RT. Patients on RT
      had a higher rate of cerebral bleeding. CONCLUSIONS: In this cohort of cancer
      patients with VTE, a significant proportion of them received RT before VTE, the
      latter experienced a higher risk of cerebral bleeding.

PMID- 28427528
TI  - Mechanisms of chemotherapy-induced ovarian damage in breast cancer patients.
AB  - Fertility preservation in breast cancer patients is an increasingly relevant
      topic. In the present paper we review available data on the mechanism of ovarian
      damage caused by anticancer agents currently used for the treatment of breast
      cancer. We also describe current methods to preserve fertility including oocytes
      or ovarian tissue freezing and administration of LH-RHa during chemotherapy. The
      aim of the paper is to provide clinical oncologists with an adequate knowledge of
      the subject to enable them to give a correct counselling to young women that must
      receive chemotherapy and want to increase their possibilities of maintaining
      fertility.

PMID- 28427529
TI  - Primary central nervous system lymphoma.
AB  - Primary CNS lymphomas (PCNSL) represent a subgroup of malignancies with specific
      characteristics, aggressive course, and unsatisfactory outcome in contrast with
      other lymphomas comparable for tumour burden and/or histological type. Despite a
      high chemo- and radiosensitivity, remissions are frequently shortlasting, mainly
      because the blood brain-barrier limits the access of many drugs to the CNS.
      Moreover, survivor patients are at high risk of developing severe treatment
      related toxicity, mainly disabling neurotoxicity, raising the question of how to
      balance therapy intensification with side-effects control. Although the prognosis
      remains poor, it has significantly improved over the past two decades as a result
      of better treatment strategies with a curative aim. Surgery has no impact on
      survival, and is reserved to diagnosis by stereotactic biopsy. Actual front-line
      therapy consists of high-dose methotrexate-based poly-chemotherapy. The optimal
      drugs combination has not yet been identified even if there is a suggestion for a
      synergistic role for the adjunction of cytarabine, thiotepa, and rituximab.
      Radiotherapy retains an important role as salvage therapy in refractory/relapsing
      patients, while its use is more debated in the setting of response consolidation
      in patients who achieve a complete remission after induction chemotherapy. High
      dose chemotherapy supported by autologous stem-cell transplantation is
      increasingly used as an effective method aimed to control microscopic disease,
      and the pros and contras of this approach are outlined.

PMID- 28427530
TI  - Phenolic Compounds and Its Bioavailability: In Vitro Bioactive Compounds or
      Health Promoters?
AB  - Botanical preparations present a widespread and secular history of use. In fact,
      natural matrices possess a rich pool of phytochemicals, with promising biological
      effects. Among them, phenolic compounds have revealed to confer very important
      attributes to improve the well-being and longevity of worldwide population.
      Numerous in vitro studies have been carried out evaluating the wide spectrum of
      bioactivities of phenolic compounds, including its health effects, but through in
      vivo experiments some of these previous results cannot be properly confirmed, and
      considerable variations are observed. Pharmacokinetic parameters, including the
      assessment of bioavailability and bioefficacy of phenolic compounds, still
      continue to be largely investigated and considered a great hot topic among the
      food science and technology researchers. Thus, based on these crucial aspects,
      this chapter aims to provide an extensive approach about the question of the
      bioavailability of phenolic compounds, describing its biosynthetic routes and
      related mechanisms of action; to focus on the current facts and existing
      controversies, highlighting the importance of in vivo studies and the impact of
      phenolic compounds on the quality of life and longevity.

PMID- 28427531
TI  - Improvement of Soybean Products Through the Response Mechanism Analysis Using
      Proteomic Technique.
AB  - Soybean is rich in protein/vegetable oil and contains several phytochemicals such
      as isoflavones and phenolic compounds. Because of the predominated nutritional
      values, soybean is considered as traditional health benefit food. Soybean is a
      widely cultivated crop; however, its growth and yield are markedly affected by
      adverse environmental conditions. Proteomic techniques make it feasible to map
      protein profiles both during soybean growth and under unfavorable conditions. The
      stress-responsive mechanisms during soybean growth have been uncovered with the
      help of proteomic studies. In this review, the history of soybean as food and the
      morphology/physiology of soybean are described. The utilization of proteomics
      during soybean germination and development is summarized. In addition, the stress
      responsive mechanisms explored using proteomic techniques are reviewed in
      soybean.

PMID- 28427532
TI  - Nanotechnology for Food Packaging and Food Quality Assessment.
AB  - Nanotechnology has paved the way to innovative food packaging materials and
      analytical methods to provide the consumers with healthier food and to reduce the
      ecological footprint of the whole food chain. Combining antimicrobial and
      antifouling properties, thermal and mechanical protection, oxygen and moisture
      barrier, as well as to verify the actual quality of food, e.g., sensors to detect
      spoilage, bacterial growth, and to monitor incorrect storage conditions, or
      anticounterfeiting devices in food packages may extend the products shelf life
      and ensure higher quality of foods. Also the ecological footprint of food chain
      can be reduced by developing new completely recyclable and/or biodegradable
      packages from natural and eco-friendly resources. The contribution of
      nanotechnologies to these goals is reviewed in this chapter, together with a
      description of portable devices ("lab-on-chip," sensors, nanobalances, etc.)
      which can be used to assess the quality of food and an overview of regulations in
      force on food contact materials.

PMID- 28427533
TI  - Influence of High Hydrostatic Pressure Technology on Wine Chemical and Sensorial
      Characteristics: Potentialities and Drawbacks.
AB  - During last years, scientific research on high hydrostatic pressure (HHP) as a
      nonthermal processing technology for preservation or aging of wine has increased
      substantially. HHP between 200 and 500MPa is able to inactivate bacteria and
      yeasts in red and white wines, suggesting that it may be used for wine
      preservation. However, these treatments have been shown to promote changes on
      sensorial and physicochemical characteristics in both red and white wines, not
      immediately in the first month, but along storage. The changes are observed in
      wine color, aroma, and taste due mainly to reactions of phenolic compounds,
      sugars, and proteins. These reactions have been associated with those observed
      during wine aging, leading to aged-like wine characteristics perceived by
      sensorial analysis. This chapter will present the influence of HHP technology on
      wine chemical and sensorial characteristics, criticaly discussing its
      potentialities and drawbacks. The appropriate use of HHP, based on the scientific
      knowledge of the reactions occuring in wine promoted by HHP, will allow to
      exploit this technology for wine production achieving distinct characteristics to
      address particular market and consumer demands.

PMID- 28427534
TI  - Methodologies for the Characterization of the Quality of Dairy Products.
AB  - The growing interest of consumers in food quality and safety issues has
      contributed to the increasing demand for sensitive and rapid analytical
      technologies. Physicochemical, textural, sensory, etc., methods have been used to
      evaluate the quality and authenticity of milk and dairy products. Despite the
      importance of these standard methods, they are expensive and time consuming.
      Recently, spectroscopic methods have shown great potential due to speed of
      analysis, minimal sample preparation, high repeatability, low cost, and, most of
      all, the fact that these techniques are noninvasive and nondestructive and,
      therefore, could be applied to any on-line monitoring system. This chapter gave
      examples of the application of the most commonly traditional methods for the
      determination of the quality of milk and dairy products. A special focus is
      devoted to the use of infrared and fluorescence spectroscopies for the evaluation
      of the quality of dairy products.

PMID- 28427535
TI  - Pathogens of Food Animals: Sources, Characteristics, Human Risk, and Methods of
      Detection.
AB  - Pathogens associated with food production (livestock) animals come in many forms
      causing a multitude of disease for humans. For the purpose of this review, these
      infectious agents can be divided into three broad categories: those that are
      associated with bacterial disease, those that are associated with viruses, and
      those that are parasitic in nature. The goal of this chapter is to provide the
      reader with an overview of the most common pathogens that cause disease in humans
      through exposure via the food chain and the consequence of this exposure as well
      as risk and detection methods. We have also included a collection of unusual
      pathogens that although rare have still caused disease, and their recognition is
      warranted in light of emerging and reemerging diseases. These provide the reader
      an understanding of where the next big outbreak could occur. The influence of the
      global economy, the movement of people, and food makes understanding production
      animal-associated disease paramount to being able to address new diseases as they
      arise.

PMID- 28427536
TI  - Health Risks of Food Oxidation.
AB  - The impact of dietary habits on our health is indisputable. Consumer's concern on
      aging and age-related diseases challenges scientists to underline the potential
      role of food on the extension and guarantee of lifespan and healthspan. While
      some dietary components and habits are generally regarded as beneficial for our
      health, some others are being found to exert potential toxic effects and hence,
      contribute to the onset of particular health disorders. Among the latter, lipid
      and protein oxidation products formed during food production, storage,
      processing, and culinary preparation have been recently identified as potentially
      harmful to humans. Upon intake, food components are further degraded and oxidized
      during the subsequent digestion phases and the pool of compounds formed in the
      lumen is in close contact with the lamina propria of the intestines. Some of
      these oxidation products have been found to promote inflammatory conditions in
      the gut (i.e., bowel diseases) and are also reasonably linked to the onset of
      carcinogenic processes. Upon intestinal uptake, some species are distributed by
      the bloodstream causing an increase in oxidative stress markers and impairment of
      certain physiological processes through alteration of specific gene expression
      pathways. This chapter summarizes the most recent discoveries on this topic with
      particular stress on challenges that we face in the near future: understanding
      the molecular basis of disease, the suitability of using living animals vs in
      vitro model systems and the necessity of using massive genomic techniques and
      versatile mass spectrometric technology.

PMID- 28427537
TI  - Metabolomics, Nutrition, and Potential Biomarkers of Food Quality, Intake, and
      Health Status.
AB  - Diet, dietary patterns, and other environmental factors such as exposure to
      toxins are playing an important role in the prevention/development of many
      diseases, like obesity, type 2 diabetes, and consequently on the health status of
      individuals. A major challenge nowadays is to identify novel biomarkers to detect
      as early as possible metabolic dysfunction and to predict evolution of health
      status in order to refine nutritional advices to specific population groups.
      Omics technologies such as genomics, transcriptomics, proteomics, and
      metabolomics coupled with statistical and bioinformatics tools have already shown
      great potential in this research field even if so far only few biomarkers have
      been validated. For the past two decades, important analytical techniques have
      been developed to detect as many metabolites as possible in human biofluids such
      as urine, blood, and saliva. In the field of food science and nutrition, many
      studies have been carried out for food authenticity, quality, and safety, as well
      as for food processing. Furthermore, metabolomic investigations have been carried
      out to discover new early biomarkers of metabolic dysfunction and predictive
      biomarkers of developing pathologies (obesity, metabolic syndrome, type-2
      diabetes, etc.). Great emphasis is also placed in the development of
      methodologies to identify and validate biomarkers of nutrients exposure.

PMID- 28427538
TI  - Preface.

PMID- 28427539
TI  - The role of serum amyloid A staining of granulomatous tissues for the diagnosis
      of sarcoidosis.
AB  - BACKGROUND: Previous studies demonstrated that SAA staining of sarcoidosis
      granulomas was qualitatively and quantitatively different from other
      granulomatous diseases. These data suggest that positive SAA staining of
      granulomatous tissue may have adequate specificity to establish a diagnosis of
      sarcoidosis. Our objective was to determine the diagnostic specificity of SAA
      staining for sarcoidosis relative to other granulomatous disorders. METHODS:
      Pathological specimens demonstrating granulomatous inflammation were
      retrospectively identified at one institution, plus 4 specimens were obtained
      from New York City firefighters with biopsy-confirmed World Trade Center
      "sarcoidosis-like" pulmonary disease. Specimens were analyzed if specific
      diagnoses related to the granulomatous inflammation were confirmed through
      medical record review. SAA staining was performed using previously developed
      methods. Two pathologists, blinded to each other and the diagnoses, determined if
      the stained material was SAA positive or negative. Discordant results were
      adjudicated by the two pathologists. MEASUREMENTS AND MAIN RESULTS: 106 specimens
      were analyzed from 100 patients, with 36 biopsies (34%) from sarcoidosis tissues
      and 70 (66%) from other granulomatous disorders. The Cohen Kappa correlation
      between the two pathologists for SAA staining positivity was excellent (0.85,
      0.73-0.98). The overall specificity of SAA staining for the diagnosis of
      sarcoidosis was 84% (59/70). The sensitivity was 44% (16/36). CONCLUSIONS:
      Although SAA staining of various granulomatous tissues was fairly specific for
      the diagnosis of sarcoidosis, the specificity was inadequate for SAA staining to
      be used as a diagnostic test for sarcoidosis in isolation. These data suggest
      that SAA production may not be a universal mechanism in the development of
      sarcoidosis.

PMID- 28427540
TI  - High resolution computed tomography pattern of usual interstitial pneumonia in
      rheumatoid arthritis-associated interstitial lung disease: Relationship to
      survival.
AB  - PURPOSE: Interstitial lung disease is a common extra-articular manifestation of
      rheumatoid arthritis (RA-ILD) and is associated with significant morbidity and
      mortality. However, limited data exist regarding predictors of mortality. We
      sought to examine the prognostic value of the high-resolution computed tomography
      (HRCT) patterns in patients with RA-ILD. MATERIALS AND METHODS: RA-ILD patients
      with HRCT patterns of usual interstitial pneumonia (UIP) or nonspecific
      interstitial pneumonia (NSIP) were identified among a longitudinal cohort of
      individuals evaluated at National Jewish Health. A total of 158 subjects were
      included in the study. For each subject, the earliest available HRCT was reviewed
      independently by two expert thoracic radiologists blinded to clinical data. HRCT
      patterns were classified as demonstrating definite UIP, possible UIP, or NSIP.
      Kaplan-Meier curves were generated and survival was compared among the three
      patterns using a log rank test for trend. RESULTS: One hundred subjects (63%) had
      HRCT findings classified as definite UIP, 23 (15%) as possible UIP and 35 (22%)
      as NSIP. No difference in survival was seen between subjects with definite UIP
      versus those with possible UIP. The combined group of subjects with either
      definite- or possible UIP had significantly worse survival than those with NSIP
      (log-rank p = 0.03). CONCLUSIONS: In patients with RA-ILD, patients with either
      definite UIP or possible UIP have equally poor survival when compared to those
      with an NSIP pattern.

PMID- 28427541
TI  - Long-term safety and efficacy of glycopyrrolate/formoterol metered dose inhaler
      using novel Co-SuspensionTM Delivery Technology in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: The long-term safety and efficacy of a novel Co-SuspensionTM Delivery
      Technology glycopyrrolate (GP)/formoterol fumarate (FF) 18/9.6 MUg fixed-dose
      combination metered dose inhaler (GFF MDI) were investigated in a 28-week safety
      extension study (PINNACLE-3, NCT01970878) of two randomized controlled Phase III
      trials (PINNACLE-1 and -2; NCT01854645 and NCT01854658) in subjects with moderate
      to-very severe chronic obstructive pulmonary disease (COPD). METHODS: Subjects
      completing 24 weeks' treatment with GFF MDI, GP MDI, FF MDI (all twice-daily) or
      open-label tiotropium 18 MUg (once-daily) in PINNACLE-1 or -2 were randomly
      selected to continue treatment for 28 weeks. The target enrollment for PINNACLE-3
      was 850 subjects. Safety and efficacy were evaluated over 52 weeks. RESULTS: Of
      3274 subjects randomized to active treatment in PINNACLE-1 or -2, 892 entered
      PINNACLE-3. Incidences of adverse events, serious adverse events and major
      adverse cardiovascular events were similar across treatment groups with no
      unexpected safety findings. For change from baseline in morning pre-dose trough
      forced expiratory volume in 1 s (FEV1), treatment differences for GFF MDI versus
      GP MDI, FF MDI and open-label tiotropium over 52 weeks were 57, 65 and 25 mL,
      respectively (p <= 0.0117). Average daily rescue medication use was significantly
      reduced for GFF MDI versus GP MDI and open-label tiotropium (p <= 0.0002).
      Statistically significant improvements were observed with GFF MDI versus
      monocomponents in Self-Administered Computerized Transition Dyspnea Index focal
      score, and in St George's Respiratory Questionnaire total score versus GP MDI.
      CONCLUSIONS: Results confirmed the long-term safety and tolerability of GFF MDI
      18/9.6 MUg twice-daily in subjects with moderate-to-very severe COPD.
      Improvements in efficacy endpoints were also sustained over 52 weeks.

PMID- 28427542
TI  - Recurrent respiratory papillomatosis: A state-of-the-art review.
AB  - Recurrent respiratory papillomatosis (RRP) is a benign disease of the upper aero
      digestive tract caused by human papillomavirus (HPV) infection, which affects
      children and young adults. The aim of this review is to describe the main
      etiological, epidemiological, clinical, diagnostic, and treatment aspects of RRP.
      Most infections in children occur at birth, during passage through the birth
      canals of contaminated mothers. In adults, HPV is transmitted sexually.
      Papillomas usually appear as exophytic nodules, primarily in the larynx, but
      occasionally involving the nasopharynx, tracheobronchial tree, and pulmonary
      parenchyma. The disease course is unpredictable, ranging from spontaneous
      remission to aggressive persistent or recurrent disease. Although it occurs
      rarely, RRP has the potential for malignant transformation to squamous cell
      carcinoma. Clinically, RRP usually presents with nonspecific symptoms of airway
      involvement, including chronic cough, hoarseness, wheezing, voice change,
      stridor, and chronic dyspnea. Helical computed tomography (CT) is highly accurate
      for the identification and characterization of focal or diffuse airway narrowing
      caused by nodular vegetant lesions. The typical CT pattern of lung papillomatosis
      consists of numerous multilobulated nodular lesions of various sizes, frequently
      cavitated, scattered throughout the lungs. Bronchoscopy is the most reliable
      method for the diagnosis of RRP; it enables direct visualization of lesions in
      the central airways and collection of biopsy samples for histopathological
      diagnosis, and is also useful for therapeutic planning. The definitive diagnosis
      of RRP is based on histopathological analysis. Currently, no definitive curative
      treatment for RRP is available; despite the availability of adjunctive
      treatments, surgery remains the mainstay of treatment.

PMID- 28427543
TI  - Changes in physical activity and sedentary behaviour following pulmonary
      rehabilitation in patients with COPD.
AB  - A more profound investigation about the responses in activity levels following
      pulmonary rehabilitation (PR) in patients with COPD is needed. We aimed to
      describe groups of patients with COPD according to patterns of change in physical
      activity and sedentary behaviour following PR. 90 patients with COPD (60% male;
      mean age 67 +/- 8; median FEV1 47 (32-62) %pred) completed a comprehensive PR
      programme. A triaxial accelerometer was used to assess the time in sedentary
      behaviour, light activities and moderate-to-vigorous physical activity (MVPA).
      Additionally, exercise capacity, quality of life, and symptoms of anxiety and
      depression were assessed before and after PR. Six groups with different patterns
      of change in physical activity and sedentary behaviour were identified. The two
      most prevalent patterns were represented by good responders (increase in physical
      activity and reduction in sedentary behaviour, 34%) and poor responders (decrease
      in physical activity and increase in sedentary behaviour, 30%). Good responders
      had greater improvements in six-minute walk distance (6MWD) and symptoms of
      depression than poor responders (P < 0.05 for all). Strong correlation was found
      between changes in sedentary behaviour and changes in light activities (rs = 
      0.89; P < 0.0001). Changes in 6MWD correlated fairly with changes in sedentary
      behaviour (rs = -0.26), light activities (rs = 0.25), and MVPA (rs = 0.24); P <
      0.05 for all. Different patterns of change in activity levels following PR can be
      found in patients with COPD. Focusing on light physical activities might be a
      potential strategy to make patients less sedentary, but for this to be achieved
      prior (or at least parallel) improvements in functional capacity seem to be
      necessary.

PMID- 28427544
TI  - What's the secret behind the benefits of whole-body vibration training in
      patients with COPD? A randomized, controlled trial.
AB  - BACKGROUND: Several studies have shown that whole-body vibration training (WBVT)
      improves exercise capacity in patients with severe COPD. The aim of this study
      was to investigate the determinants of improved exercise capacity following WBVT.
      METHODS: Seventy-four COPD patients (FEV1: 34 +/- 9%predicted) were recruited
      during a 3-week inpatient pulmonary rehabilitation (PR) program. Conventional
      endurance and strength exercises were supplemented with self-paced dynamic squat
      training sessions (4bouts*2min, 3times/wk). Patients were randomly allocated to
      either a WBVT-group performing squat training on a side-alternating vibration
      platform (Galileo) at a high intensity (24-26 Hz) or a control group performing
      squat training without WBVT. RESULTS: Patients in the WBVT group significantly
      improved postural balance in several domains compared to the control-group (i.e.
      tandem stance: WBVT +20% (95%CI 14 to 26) vs. control -10% (95%CI 6 to 15), p <
      0.001; one-leg stance: WBVT +11% (95%CI 4 to 19) vs. control -8% (95%CI -19 to
      3), p = 0.009). Six-minute walk distance and muscle power but not muscle strength
      were also significantly improved compared to control group. CONCLUSIONS:
      Implementation of WBVT improves postural balance performance and muscle power
      output. The neuromuscular adaptation related to improved balance performance may
      be an important mechanism of the improvement in exercise capacity after WBVT
      especially in COPD patients with impaired balance performance and low exercise
      capacity.

PMID- 28427545
TI  - Corrigendum to "Efficacy and safety comparison: Fluticasone furoate and
      fluticasone propionate, after step down from fluticasone furoate/vilanterol in
      Japanese patients with well-controlled asthma, a randomized trial" [Respir. Med.
      120 (November 2016) 78-86].

PMID- 28427546
TI  - Is the bronchodilator test an useful tool to measure asthma control?
AB  - INTRODUCTION: Asthma control includes the control of symptoms and future risk. We
      sought to evaluate the usefulness of the degree of spirometric reversibility of
      the forced expiratory volume in one second (FEV1) as the target parameter of
      control. METHODOLOGY: Patients with bronchial asthma were followed up for one
      year. The clinical, functional, inflammatory and control parameters of the asthma
      were collected. The area under the curve (AUC) was estimated to establish the
      cutoff point of the post-bronchodilator FEV1 reversibility in relation to non
      control asthma. In the univariate analysis, the differences between groups were
      studied based on the degree of estimated reversibility. Factors with a
      significance <0.1 were included in the multivariate analysis by binary logistic
      regression. RESULTS: A total of 407 patients with a mean age of 38.1 +/- 16.7
      years were included. When the patients were grouped into controlled and non
      controlled groups, compared with post-bronchodilator FEV1 reversibility, the
      cutoff point obtained for the non-controlled group was >=10% (sensitivity: 65.8%,
      specificity: 48.4%, positive predictive value: 69.5%, and AUC: 0.619 [0.533
      0.700], p < 0.01). In the year-long follow-up of this group (post-bronchodilator
      FEV1 >=10), an increased use of relief medication was observed, along with a
      significantly progressive drop in post-bronchodilator FEV1 and post
      bronchodilator FEV1/FVC (forced expiratory volume in one second/forced vital
      capacity). CONCLUSIONS: Spirometric reversibility can be useful in assessing
      control in asthmatic patients and can predict future risk parameters. The cutoff
      point related to the non-control of asthma found in our work was >=10%.

PMID- 28427547
TI  - Qualitative evaluation of the St George's Respiratory Questionnaire in patients
      with severe asthma.
AB  - PURPOSE: Content validity is the extent to which a patient-reported outcome
      measure evaluates the concepts most relevant to a patient's condition and
      treatment. The St George's Respiratory Questionnaire (SGRQ) has been validated in
      a range of respiratory conditions. This study evaluated the content validity of
      the SGRQ in patients with severe asthma. METHODS: A qualitative study, guided by
      a protocol, which included concept elicitation and cognitive debriefing of the
      SGRQ, was conducted in patients aged >=18 years with history of severe asthma and
      blood eosinophil counts of >=150/MUL (past month) or >=300/MUL (past 12 months).
      Patients were recruited until saturation for concept elicitation was achieved
      (i.e. no additional concepts identified). Concepts identified by the patients
      were then mapped to the SGRQ. RESULTS: 18 patient interviews provided concept
      saturation. Concept elicitation confirmed that the SGRQ includes the commonly
      reported asthma symptoms and their impact on daily life. In total, 89-100% of
      patients routinely experienced cough, nighttime awakenings, shortness of breath,
      chest tightness, sleep difficulty, phlegm/mucus, and wheezing. Patients reported
      asthma impacting daily and physical activities, mood and sleep. Cognitive
      interviewing confirmed that patients understood the instructions, items and
      response options in the SGRQ. Nearly half of the concepts in the SGRQ were
      endorsed by >=12 patients; of the 17 items with scoring weights >=85, 11 were
      mentioned by >=12 patients. CONCLUSIONS: This study demonstrates that the SGRQ is
      a relevant, comprehensive and content-valid instrument to assess health status in
      patients with severe asthma.

PMID- 28427548
TI  - Autosomal dominant gain of function STAT1 mutation and severe bronchiectasis.
AB  - BACKGROUND: In a substantial number of patients with non-cystic fibrosis (CF)
      bronchiectasis an etiology cannot be found. Various complex immunodeficiency
      syndromes account for a significant portion of these patients but the mechanism
      elucidating the predisposition for suppurative lung disease often remains
      unknown. OBJECTIVE: To investigate the cause and mechanism predisposing a patient
      to severe bronchiectasis. METHODS: A patient presenting with severe non-CF
      bronchiectasis was investigated. Whole exome analysis (WES) was performed and
      complemented by extensive immunophenotyping. RESULTS: The genetic analysis
      revealed an autosomal dominant gain-of-function mutation (AD- GOF) in the signal
      transducer and activator of transcription 1 (STAT1) in the patient. STAT1
      phosphorylation studies showed increased phosphorylation of STAT1 after
      stimulation with interferon gamma (IFN-gamma). Immunophenotyping showed normal
      counts of CD4 and CD8 T cells, B and NK cells, but a reduction of all memory B
      cells especially class switched memory B cells. Minor changes in the CD8 T cell
      subpopulations were seen. CONCLUSIONS: Early use of WES in the investigation of
      non-CF bronchiectasis was highly advantageous. The degree of impairment in class
      switched memory B cells may predispose patients with AD- GOF mutations in STAT1
      to suppurative sinopulmonary disease.

PMID- 28427549
TI  - Lung diseases associated with hydrocarbon exposure.
AB  - The human race has been exposed to the potential toxicity of hydrocarbons,
      whether by the inhaled or ingested route, for thousands of years and the
      consequent inflammatory reaction in the lungs depends on the degree of exposure,
      volatility and viscosity of the particular hydrocarbon in question. Heating,
      lighting, transportation, industry and nature all provide the potential for both
      inhalation and/or ingestion of hydrocarbons. Some forms, such as those related to
      petroleum products, e.g. diesel exhaust particles (DEP) and polycyclic aromatic
      hydrocarbons (PAH) have been shown to cause both malignant and non-malignant
      respiratory diseases. Accidental ingestion represents another significant
      exposure risk and we now have increasing evidence that pollutant particles may
      adsorb allergens to their surface and potentially enhance the allergic response.
      It seems unlikely that this potential will significantly decrease in the near
      future and depending on individual socio-economic circumstances, work environment
      and habitation, the risks of significant lung disease will vary. This review
      outlines the domestic, outdoor, occupational and natural sources of hydrocarbon
      exposure and considers the evidence relating to radiological and pathological
      lung changes in both animals and man. The acute effects of hydrocarbon toxicity
      are well recognised but the effects of longer term, lower exposure, and the
      mechanisms of their toxicity, require further research.

PMID- 28427550
TI  - Home-made spacer as an auxiliary device in administration of beclomethasone via
      pressurized metered dose inhaler for asthma control. A randomized controlled
      pragmatic trial.
AB  - BACKGROUND: Holding chambers or spacers can enhance the efficacy of pressurized
      metered dose inhalers (pMDI) in delivering inhaled medications, as they reduce
      the need for hand-breath coordination and improve lower airways deposition.
      Nevertheless, their cost can be high for patients in low-income countries.
      OBJECTIVE: To compare asthma control achieved with beclomethasone-dipropionate
      administered through a hydrofluoroalkane-driven pMDI (BDp-pMDI) coupled to a home
      made spacer (HmS) or to a valved commercial spacer (VCS) as auxiliary devices.
      METHODS: Sixty-three patients with poorly controlled asthma that had a BDp-pMDI
      prescription were randomized to use the inhaler coupled to a HmS made of 500 ml
      plastic bottles (Group HmS, n = 32) or to a VCS (Group VCS, n = 31) for 60 days.
      All were given training sessions. Asthma control was assessed through the Asthma
      Control Test (ACT) and forced expiratory volume in the first second (FEV1), both
      measured before, and 30 and 60 days after treatment began. RESULTS: Both groups
      showed significant improvement in ACT scores after 30 and 60 days compared to
      baseline values (an increase of 7 and 7.8 points for the HmS group and 5.9 and
      7.0 points for the VCS group, respectively, p < 0.001). There was no
      statistically significant difference in ACT scores between groups at any
      observation time (P = 0.261). FEV1 showed the same behavior. CONCLUSIONS: A
      similar level of asthma control was achieved with beclomethasone-dipropionate
      administered through a pMDI whether the inhaler was coupled to the HmS or VCS.
      These results are significant for asthma control planning strategies in low
      income communities. (Trial Register Number: RBR-5x4dc9).

PMID- 28427551
TI  - Cardiopulmonary exercise factors predict survival in patients with advanced
      interstitial lung disease referred for lung transplantation.
AB  - BACKGROUND: The purpose of this work was to determine if parameters assessed
      during Cardiopulmonary Exercise Testing (CPET) while using supplemental oxygen
      can independently predict one-year transplant-free survival in patients with
      Interstitial Lung Disease (ILD) referred for lung transplant evaluation. METHODS:
      We performed a chart review of patients with ILD who completed CPET with 30% FiO2
      and gathered spirometry, pulmonary hemodynamic, six-minute walk, and CPET data.
      The primary end-point was death or lung transplantation within one-year of CPET.
      RESULTS: The final data set included 192 patients. 79 patients died/underwent
      transplant, 113 survived transplant-free. Multivariable Cox regression revealed
      peak workload % predicted, nadir CPET SpO2, and FVC% predicted as independent
      predictors of one-year transplant-free survival. Of the independent predictors of
      survival, receiver operating characteristics analysis revealed peak workload
      %predicted cutoff of 35% to be highly discriminatory, more so than nadir CPET
      SpO2 or FVC % predicted in identifying patients at risk for one-year mortality or
      transplant (peak workload % predicted < 35% HR = 4.71, 95% CI = 2.64-8.38 and
      area under the curve (AUC) = 0.740, nadir CPET SpO2 < 86% HR = 2.27, 95%CI = 1.41
      3.68, AUC = 0.645, FVC %predicted <45% HR = 1.82, 95% CI = 1.15-2.87, AUC =
      0.624). CONCLUSION: Peak workload % predicted, nadir CPET SpO2, and FVC%
      predicted in ILD patients referred for lung transplant evaluation are
      independently predictive of one-year mortality or need for transplant.

PMID- 28427552
TI  - Integrating the microbiota of the respiratory tract with the unified airway
      model.
AB  - The unified airway model has developed from indications that the upper and lower
      respiratory tracts share key elements of pathogenesis. These shared traits likely
      extend to similar niche characteristics that support bacterial communities, and
      as such, we suspect that similar microbes exist on upper and lower respiratory
      tract epithelium. Over the past decade and a half there have been significant
      improvements in microbiological identification and analysis due to the
      development of new molecular technologies, including next-generation sequencing.
      In this review, we provide an overview of the modern collection and sequencing
      methods involved in respiratory microbiota research, and outline the specific
      microbial communities that have been found to be associated with the healthy and
      diseased human respiratory tract. Demonstration of a remarkable similarity
      between the upper and lower respiratory tract in terms of microbiological
      presence adds further corroboration to the existence of a unified airway.

PMID- 28427553
TI  - Familial pulmonary fibrosis: Clinical and radiological characteristics and
      progression analysis in different high resolution-CT patterns.
AB  - BACKGROUND: Familial pulmonary fibrosis (FPF) is defined as an idiopathic diffuse
      parenchymal lung disease affecting two or more members of the same primary
      biological family. The aim of the present study was to contribute to the
      clinical, functional and radiological characterisation of FPF with particular
      regards to disease progression and survival. METHODS: Baseline clinical,
      functional and radiological data of a FPF population (n = 46 patients) were
      retrospectively collected and analysed according to the 2011 IPF guidelines HRCT
      classification. A PFT follow-up after 1-year and survival analysis was conducted
      among to different HRCT patterns. RESULTS: 22 female and 24 male patients (age at
      diagnosis 58.5 +/- 9.7 years-old), belonging to 30 families, were included in
      this study. Radiological analysis demonstrated the presence of a UIP pattern at
      HRCT in 54.3% of patients, Poss-UIP in 21.8% and Incon-UIP in 23.9%. Incon-UIP
      patients were younger and more frequently female. Pulmonary function tests showed
      a restrictive ventilatory defect in patients with UIP and Incon-UIP patterns,
      while Poss-UIP patients had normal volumes with only a mild reduction of DLCO.
      BAL composition revealed increased lymphocytes percentage in Incon-UIP patients.
      Respiratory functional 1-year follow-up showed a significant worsening in UIP
      patients only. HRCT pattern progression was only demonstrated from Poss-UIP to
      UIP (18% of patients). Median survival was not statistically different among the
      3 HRCT groups, although Poss-UIP patients presented a better outcome.
      CONCLUSIONS: FPF has been confirmed to be a complex condition with poor
      prognosis. The present study firstly analysed functional and radiological follow
      up data of patients with FPF, showing that it may manifests with several HRCT
      patterns with different rates of progression, in which Possible UIP and UIP could
      be considered phases of the same disease and Inconsistent UIP patients may
      represent a different clinical and radiological condition.

PMID- 28427554
TI  - Clinical and hemodynamic improvements after adding ambrisentan to background
      PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a
      suboptimal therapeutic response (ATHENA-1).
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a condition which may lead to
      right ventricular failure and premature death. While recent data supports the
      initial combination of ambrisentan (a selective ERA) and tadalafil (a PDE5i) in
      functional class II or III patients, there is no published data describing the
      safety and efficacy of ambrisentan when added to patients currently receiving a
      PDE5i and exhibiting a suboptimal response. The ATHENA-1 study describes the
      safety and efficacy of the addition of ambrisentan in this patient population.
      METHODS: PAH patients with a suboptimal response to current PDE5i monotherapy
      were assigned ambrisentan in an open-label fashion and evaluated for up to 48
      weeks. Cardiopulmonary hemodynamics (change in PVR as primary endpoint) were
      evaluated at week 24 and functional parameters and biomarkers were measured
      through week 48. Time to clinical worsening (TTCW) and survival are also
      described. RESULTS: Thirty-three subjects were included in the analysis. At week
      24, statistically significant improvements in PVR (-32%), mPAP (-11%), and CI
      (+25%) were observed. Hemodynamic improvements at week 24 were further supported
      by improvements in the secondary endpoints: 6-min walk distance (+18 m), NT
      proBNP (-31%), and maintenance or improvement in WHO FC in 97% of patients.
      Adverse events were consistent with known effects of ambrisentan. CONCLUSION: The
      hemodynamic, functional, and biomarker improvements observed in the ATHENA-1
      study suggests that the sequential addition of ambrisentan to patients not having
      a satisfactory response to established PDE5i monotherapy is a reasonable option.

PMID- 28427555
TI  - Impact of cavity and infiltration on pulmonary function and health-related
      quality of life in pulmonary Mycobacterium avium complex disease: A 3-dimensional
      computed tomographic analysis.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary Mycobacterium avium complex (pMAC) disease
      manifests as various types of lesions, such as infiltrates, nodules, cavities,
      and bronchiectasis. However, the important determinants for clinical parameters
      in lung involvement are poorly understood. The objective of this study was to
      obtain quantitative parameters by 3-dimensional CT, and investigate the
      relationship between these parameters and the pulmonary function tests (PFTs) and
      health-related quality of life. MATERIAL AND METHODS: Quantitative analysis using
      CT was performed in 67 pMAC patients. The relationship between new quantitative
      parameters for evaluating lung involvement using 3-dimensional CT and PFTs or St
      George's Respiratory Questionnaire (SGRQ) was evaluated. RESULTS: The ratio of
      infiltration to total lung volume showed significant correlation with the PFT
      results, especially the percent-predicted forced vital capacity (%FVC; rho = 
      0.52), residual volume (rho = -0.51), and total lung capacity (rho = -0.59). The
      cavity volume was strongly correlated with the %FVC (rho = -0.78) in the cavity
      group, while the ratio of infiltration to total lung volume was strongly
      correlated with the %FVC (rho = -0.53) in the non-cavity group. The ratio of
      infiltration to total lung volume was significantly correlated with all SGRQ
      parameters (rho = 0.41-0.52) in the non-cavity group. CONCLUSIONS: Infiltration
      was an important parameter for the PFTs and SGRQ in pMAC patients according to
      the 3-dimensional CT analysis. Moreover, cavity volume was an important parameter
      of the PFTs in the cavity group. Therefore, infiltration and cavity volume are
      key features for the management of pMAC disease.

PMID- 28427556
TI  - Pirfenidone for acute exacerbation of idiopathic pulmonary fibrosis: A
      retrospective study.
AB  - BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a
      rapid and ultimately fatal condition, and no effective treatment has been
      established. Pirfenidone has antifibrotic effects in IPF; however, its efficacy
      for AE-IPF is unclear. OBJECTIVES: To evaluate the efficacy of pirfenidone for AE
      IPF. METHODS: We retrospectively reviewed the medical records of 135 IPF patients
      treated during the period from April 2008 to April 2015 and identified and
      extracted 47 AE-IPF patients (42 men, 5 women; mean age, 73.5 years). The
      clinical features and outcomes of the 20 patients treated with pirfenidone were
      compared with those of the 27 patients treated without pirfenidone. We then
      excluded the 25 patients who did not receive recombinant human soluble
      thrombomodulin (rhTM) and analyzed data from the remaining 22 patients (20 men, 2
      women; mean age, 73.7 years). Clinical features and outcomes were compared
      between the 10 patients treated with pirfenidone and the 12 patients who did not
      receive pirfenidone. RESULTS: There were no significant differences between the
      two groups in baseline characteristics, except for pirfenidone use before onset.
      Three-month survival was significantly better in patients treated with
      pirfenidone than in the control group (55% vs 34%, p = 0.042). In univariate
      analysis, nonuse of pirfenidone was a potential risk factor for death at 3 months
      (hazard ratio, 6.993; p = 0.043) in patients treated with rhTM. CONCLUSION: A
      regimen of pirfenidone combined with corticosteroids and rhTM may improve
      survival in patients with AE-IPF.

PMID- 28427557
TI  - Oxidative Stress: Love and Hate History in Central Nervous System.
AB  - Molecular oxygen is essential for aerobic organisms in order to synthesize large
      amounts of energy during the process of oxidative phosphorylation and it is
      harnessed in the form of adenosine triphosphate, the chemical energy of the cell.
      Oxygen is toxic for anaerobic organisms but it is also less obvious that oxygen
      is poisonous to aerobic organisms at higher concentrations of oxygen. For
      instance, oxygen toxicity is a condition resulting from the harmful effects of
      breathing molecular oxygen at increased partial pressures. Reactive oxygen
      species (ROS) are chemically reactive molecules containing oxygen that are formed
      as a natural byproduct of the normal metabolism of oxygen and have important
      roles in cell signaling and homeostasis. However, in pathological conditions ROS
      levels can increase dramatically. This may result in significant damage to cell
      structures. Living organisms have been adapted to the ROS in two ways: they can
      mitigate the unwanted effects through removal by the antioxidant systems and can
      advantageously use them as messengers in cell signaling and regulation of body
      functions. Some other physiological functions of ROS include the regulation of
      vascular tone, detection, and adaptation to hypoxia. In this review, we describe
      the mechanisms of oxidative damage and its relationship with the most highly
      studied neurodegenerative diseases.

PMID- 28427558
TI  - A Computational Approach to Identify the Biophysical and Structural Aspects of
      Methylenetetrahydrofolate Reductase (MTHFR) Mutations (A222V, E429A, and R594Q)
      Leading to Schizophrenia.
AB  - The association between depression and methylenetetrahydrofolate reductase
      (MTHFR) has been continually demonstrated in clinical studies, yet there are
      sparse resources available to build a relationship between the mutations
      associated with MTHFR and depression. The common mutations found to be associated
      with schizophrenia and MTHFR are A222V, E429A, and R594Q. Although abundant
      research on structural and functional effects caused by A222V mutation is
      available, very less amount of studies have been done on the other two mutants
      (E429A and R594Q). Hence in this study, a comparative analysis was carried out
      between the most common A222V mutation, a prevalent E429A mutation, and a less
      prevalent and less deleterious R594Q mutation. To predict structural
      rearrangements upon mutation, we proposed a computational pipeline using in
      silico prediction tools, molecular docking, and molecular dynamics simulation
      analysis. Since the association of flavin adenine dinucleotide (FAD) is important
      for the functioning of the protein, binding analysis between protein and the
      coenzyme was performed. This would enable us to understand the interference level
      of each mutation over FAD-binding activity. Consequently, we found that two
      mutations (A222V and E429A) showed lesser binding activity and structural
      deviations when compared to the native molecule and mutant R594Q. Comparatively,
      higher structural changes were observed with A222V mutant complex in comparison
      to other mutant complexes. Computational studies like this could render better
      insights into the structural changes in the protein and their relationship with
      the disease condition.

PMID- 28427559
TI  - Stress-Induced NLRP3 Inflammasome in Human Diseases.
AB  - Stress is a complex event that induces disturbances to physiological and
      psychological homeostasis, and it may have a detrimental impact on certain brain
      and physiological functions. In the last years, a dual role of the stress effect
      has been studied in order to elucidate the molecular mechanism by which can
      induce physiological symptoms after psychological stress exposition and vice
      versa. In this sense, inflammation has been proposed as an important starring.
      And in the same line, the inflammasome complex has emerged to give responses
      because of its role of stress sensor. The implication of the same complex, NLRP3
      inflammasome, in different diseases such as cardiovascular, neurodegenerative,
      psychiatric, and metabolic diseases opens a door to develop new therapeutic
      perspectives.

PMID- 28427560
TI  - Stress-Adaptive Response in Ovarian Cancer Drug Resistance: Role of TRAP1 in
      Oxidative Metabolism-Driven Inflammation.
AB  - Metabolic reprogramming is one of the most frequent stress-adaptive response of
      cancer cells to survive environmental changes and meet increasing nutrient
      requirements during their growth. These modifications involve cellular
      bioenergetics and cross talk with surrounding microenvironment, in a dynamic
      network that connect different molecular processes, such as energy production,
      inflammatory response, and drug resistance. Even though the Warburg effect has
      long been considered the main metabolic feature of cancer cells, recent reports
      identify mitochondrial oxidative metabolism as a driving force for tumor growth
      in an increasing number of cellular contexts. In recent years, oxidative
      phosphorylation has been linked to a remodeling of inflammatory response due to
      autocrine or paracrine secretion of interleukines that, in turn, induces a
      regulation of gene expression involving, among others, molecules responsible for
      the onset of drug resistance. This process is especially relevant in ovarian
      cancer, characterized by low survival, high frequency of disease relapse and
      chemoresistance. Recently, the molecular chaperone TRAP1 (tumor necrosis factor
      associated protein 1) has been identified as a key junction molecule in these
      processes in ovarian cancer: in fact, TRAP1 mediates a metabolic switch toward
      oxidative phosphorylation that, in turn, triggers cytokines secretion, with
      consequent gene expression remodeling, finally leading to cisplatin resistance
      and epithelial-to-mesenchymal transition in ovarian cancer models. This review
      summarizes how metabolism, chemoresistance, inflammation, and epithelial-to
      mesenchymal transition are strictly interconnected, and how TRAP1 stays at the
      crossroads of these processes, thus shedding new lights on molecular networks at
      the basis of ovarian cancer.

PMID- 28427561
TI  - Molecular Targets of Ascochlorin and Its Derivatives for Cancer Therapy.
AB  - Cancer is an extremely complex disease comprising of a multitude of
      characteristic hallmarks that continue to evolve with time. At the genomic level,
      random mutations leading to deregulation of diverse oncogenic signal transduction
      cascades and polymorphisms coupled with environmental as well as life style
      related factors are major causative agent contributing to chemoresistance and the
      failure of conventional therapies as well as molecular targeted agents. Hence,
      there is an urgent need to identify novel alternative therapies based on
      alternative medicines to combat this dreaded disease. Ascochlorin (ASC), an
      isoprenoid antibiotic isolated initially from the fermented broth of Ascochyta
      viciae, and its synthetic derivatives have recently demonstrated substantial
      antineoplastic effects in a variety of tumor cell lines and mouse models. The
      major focus of this review article is to briefly analyze the chemopreventive as
      well as therapeutic properties of ASC and its derivatives and to identify the
      multiple molecular targets modulated by this novel class of anticancer agent.

PMID- 28427562
TI  - Cardiokines as Modulators of Stress-Induced Cardiac Disorders.
AB  - Almost 30 years ago, the protein, atrial natriuretic peptide, was identified as a
      heart-secreted hormone that provides a peripheral signal from the myocardium that
      communicates to the rest of the organism to modify blood pressure and volume
      under conditions of heart failure. Since then, additional peripheral factors
      secreted by the heart, termed cardiokines, have been identified and shown to
      coordinate this interorgan cross talk. In addition to this interorgan
      communication, cardiokines also act in an autocrine/paracrine manner to play a
      role in intercellular communication within the myocardium. This review focuses on
      the roles of newly emerging cardiokines that are mainly increased in stress
      induced cardiac diseases. The potential of these cardiokines as clinical
      biomarkers for diagnosis and prognosis of cardiac disorders is also discussed.

PMID- 28427563
TI  - Neuroinflammation in Alzheimer's Disease: The Preventive and Therapeutic
      Potential of Polyphenolic Nutraceuticals.
AB  - Brain inflammation, characterized by increased microglia and astrocyte
      activation, increases during aging and is a key feature of neurodegenerative
      diseases, such as Alzheimer's disease (AD). In AD, neuronal death and synaptic
      impairment, induced by amyloid-beta (Abeta) peptide, are at least in part
      mediated by microglia and astrocyte activation. Glial activation results in the
      sustained production of proinflammatory cytokines and reactive oxygen species,
      giving rise to a chronic inflammatory process. Astrocytes are the most abundant
      glial cells in the central nervous system and are involved in the
      neuroinflammation. Astrocytes can be activated by numerous factors, including
      free saturated fatty acids, pathogens, lipopolysaccharide, and oxidative stress.
      Activation of astrocytes produces inflammatory cytokines and the enzyme
      cyclooxygenase-2, enhancing the production of Abeta. Furthermore, the role of the
      receptor for advanced glycation end products/nuclear factor-kappaB (NF-kappaB)
      axis in neuroinflammation is in line with the nonenzymatic glycosylation theory
      of aging, suggesting a central role of the advanced glycation end products in the
      age-related cognitive and a possible role of nutraceuticals in the prevention of
      neuroinflammation and AD. However, modulation of P-glycoprotein, rather than
      antioxidant and anti-inflammatory effects, could be the major mechanism of
      polyphenolic compounds, including flavonoids. Curcumin, resvertrol, piperine, and
      other polyphenols have been explored as novel therapeutic and preventive agents
      for AD. The aim of this review is to critically analyze and discuss the
      mechanisms involved in neuroinflammation and the possible role of nutraceuticals
      in the prevention and therapy of AD by targeting neuroinflammation.

PMID- 28427565
TI  - Analyzing the Effect of V66M Mutation in BDNF in Causing Mood Disorders: A
      Computational Approach.
AB  - Mental disorders or mood disorders are prevalent globally irrespective of region,
      race, and ethnic groups. Of the types of mood disorders, major depressive
      disorder (MDD) and bipolar disorder (BPD) are the most prevalent forms of
      psychiatric condition. A number of preclinical studies emphasize the essential
      role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood
      disorders. Additionally, BDNF is the most common growth factor in the central
      nervous system along with their essential role during the neural development and
      the synaptic elasticity. A malfunctioning of this protein is associated with many
      types of mood disorders. The variant methionine replaces valine at 66th position
      is strongly related to BPD, and an individual with a homozygous condition of this
      allele is at a greater risk of developing MDD. There are very sparse reports
      suggesting the structural changes of the protein occurring upon the mutation.
      Consequently, in this study, we applied a computational pipeline to understand
      the effects caused by the mutation on the protein's structure and function. With
      the use of in silico tools and computational macroscopic methods, we identified a
      decrease in the alpha-helix nature, and an overall increase in the random coils
      that could have probably resulted in deformation of the protein.

PMID- 28427566
TI  - Preface.

PMID- 28427567
TI  - Benthic Dinoflagellate Integrator (BEDI): A new method for the quantification of
      Benthic Harmful Algal Blooms.
AB  - Despite the potential negative human health, ecological and economic impact, the
      ecology of harmful benthic dinoflagellate blooms remains largely unknown. This is
      probably due to the complex interactions among biotic and abiotic drivers that
      influence blooms, but also to the difficulty in quantifying cell abundance in a
      comparable way over large spatial and temporal scales. One of the recognized
      priorities for bHABs (benthic Harmful Algal Blooms) assessment is developing and
      standardizing methods that can provide comparable data. In this context, the
      Benthic Dinoflagellates Integrator (BEDI), a new non-destructive quantification
      method for benthic dinoflagellate abundances, has been developed and tested
      within the present study. The rationale behind the BEDI standard assessment
      method is that mechanical resuspension of cells enables the quantification of
      abundances as cells per unit of seabed surface area (i.e. cellsmm-2) or as
      Potentially Resuspended cells per unit of volume (PRcellsml-1), by integrating
      both cells in the biofilm and those in the surrounding water. Estimations of
      Ostreopsis performed with BEDI method are independent of the substratum (i.e.
      macroalgal species) or the dominant ecosystem (i.e. algal forests or turfs,
      seagrass beds, coral reefs) and potentially allow the comparison of benthic
      dinoflagellate blooms over broad temporal and spatial scales. The first
      application of the BEDI method, presented in this study, gave encouraging
      results: the characterization of blooms of Ostreopsis cf. ovata at three sites in
      the NW Mediterranean Sea is consistent with results derived from the other
      commonly applied methods. Quantification of the ratio between abundances of cells
      in the biofilm and in the surrounding water was calculated for the first time per
      unit of seabed surface area, demonstrating that the highest abundances of cells
      (the stock), and therefore the associated risk for human health, are in the
      biofilm. For risk assessment purposes, conversion values for commonly used
      monitoring alert thresholds of Mediterranean Ostreopsis blooms are provided.

PMID- 28427568
TI  - Inter and intra-specific growth and domoic acid production in relation to
      nutrient ratios and concentrations in Pseudo-nitzschia: phosphate an important
      factor.
AB  - The factors responsible for inducing the synthesis of toxins and responses from
      toxic phytoplankton blooms remain unclear. In this study we compare the influence
      of genotypic (at both the intra and interspecific levels) and environmental
      factors (nutrient concentration and ratio) on growth (in terms of cell densities)
      and domoic acid (DA) production in three Pseudo-nitzschia species: P. australis,
      P.pungens and P.fradulenta. A strong phosphate effect was detected. More
      precisely, a low initial concentration in phosphate, even at high initial
      nitrogen and silicate concentrations, induced the highest DA concentrations and
      the lowest cell densities in all strains/species studied. In contrast, a low
      initial concentration of nitrogen and silicate combined, with a higher phosphate
      concentration resulted in low cell densities, but without high DA production.
      Inter-species effects were also observed in DA production, where P. australis
      represented the most toxigenic species of all. Intra-specific variations were
      only moderate, except for a recently isolated P. australis strain, suggesting the
      influence of time since isolation on the physiology and DA production of Pseudo
      nitzschia species. Overall, the lack of strong interaction between environmental
      and genotypic factors showed that the various genotypes investigated did not
      extensively diverge in their ability to respond (in terms of DA production and
      cell densities) to contrasting nutrient supply.

PMID- 28427564
TI  - Inflammation in Epileptic Encephalopathies.
AB  - West syndrome (WS) is an infantile epileptic encephalopathy that manifests with
      infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor
      neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic
      pathologies (~60%), genetic (12%-15%), or of unknown origin. The current
      treatment options include hormonal treatment (adrenocorticotropic hormone and
      high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while
      ketogenic diet can be given as add-on treatment in refractory IS. There is a need
      to identify new therapeutic targets and more effective treatments for WS.
      Theories about the role of inflammatory pathways in the pathogenesis and
      treatment of WS have emerged, being supported by both clinical and preclinical
      data from animal models of WS. Ongoing advances in genetics have revealed
      numerous genes involved in the pathogenesis of WS, including genes directly or
      indirectly involved in inflammation. Inflammatory pathways also interact with
      other signaling pathways implicated in WS, such as the neuroendocrine pathway.
      Furthermore, seizures may also activate proinflammatory pathways raising the
      possibility that inflammation can be a consequence of seizures and epileptogenic
      processes. With this targeted review, we plan to discuss the evidence pro and
      against the following key questions. Does activation of inflammatory pathways in
      the brain cause epilepsy in WS and does it contribute to the associated
      comorbidities and progression? Can activation of certain inflammatory pathways be
      a compensatory or protective event? Are there interactions between inflammation
      and the neuroendocrine system that contribute to the pathogenesis of WS? Does
      activation of brain inflammatory signaling pathways contribute to the transition
      of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored
      targets for future therapy development for WS targeting inflammation?

PMID- 28427569
TI  - Chronic low-level exposure to the common seafood toxin domoic acid causes
      cognitive deficits in mice.
AB  - The consumption of one meal of seafood containing domoic acid (DA) at levels high
      enough to induce seizures can cause gross histopathological lesions in
      hippocampal regions of the brain and permanent memory loss in humans and marine
      mammals. Seafood regulatory limits have been set at 20mgDA/kg shellfish to
      protect human consumers from symptomatic acute exposure, but the effects of
      repetitive low-level asymptomatic exposure remain a critical knowledge gap.
      Recreational and Tribal-subsistence shellfish harvesters are known to regularly
      consume low levels of DA. The aim of this study was to determine if chronic low
      level DA exposure, at doses below those that cause overt signs of neurotoxicity,
      has quantifiable impacts on cognitive function. To this end, female C57BL/6NJ
      mice were exposed to asymptomatic doses of DA (~0.75mg/kg) or vehicle once a week
      for several months. Spatial learning and memory were tested in a radial water
      maze paradigm at one, six and 25 weeks of exposure, after a nine-week recovery
      period following cessation of exposure, and at three old age time points (18, 24
      and 28 months old). Mice from select time points were also tested for activity
      levels in a novel cage environment using a photobeam activity system. Chronic low
      level DA exposure caused significant spatial learning impairment and
      hyperactivity after 25 weeks of exposure in the absence of visible
      histopathological lesions in hippocampal regions of the brain. These cognitive
      effects were reversible after a nine-week recovery period with no toxin exposure
      and recovery was sustained into old age. These findings identify a new potential
      health risk of chronic low-level exposure in a mammalian model. Unlike the
      permanent cognitive impacts of acute exposure, the chronic low-level effects
      observed in this study were reversible suggesting that these deficits could
      potentially be managed through cessation of exposure if they also occur in human
      seafood consumers.

PMID- 28427570
TI  - High resolution mass spectrometry-based screening reveals lipophilic toxins in
      multiple trophic levels from the North Sea.
AB  - Lipophilic marine biotoxins, which are mainly produced by small dinoflagellates,
      are increasingly detected in coastal waters across the globe. As these producers
      are consumed by zooplankton and shellfish, the toxins are introduced,
      bioaccumulated and possibly biomagnified throughout marine food chains. Recent
      research has demonstrated that ultra-high performance liquid chromatography
      coupled to high-resolution mass spectrometry (UHPLC-HRMS) is an excellent tool to
      detect marine toxins in algae and seafood. In this study, UHPLC-HRMS was used to
      screen lipophilic marine biotoxins in organisms from different trophic levels of
      the Belgian coastal zone ecosystem. A total of 20 tentatively identified
      lipophilic compounds was detected. Hereby, the trophic transfer of lipophilic
      marine biotoxins to the upper trophic level was considered to be rather limited.
      Furthermore, 36% of the compounds was clearly transferred between different
      organisms. A significant biotransformation of compounds from the okadaic acid and
      spirolide toxin groups was observed (64%), mainly in filter feeders. Through a
      multi-targeted approach, this study showed that marine organisms in the Belgian
      coastal zone are exposed to a multi-toxin mixture. Further research on both
      single compound and interactive toxic effects of the frequently detected
      lipophilic marine toxin ester metabolites throughout the food chain is therefore
      needed. As a future perspective, confirmatory identification of potential toxins
      by studying their fragmentation spectra (using new tools such as hybrid
      quadrupole Q-ExactiveTM Orbitrap-MS) is designated.

PMID- 28427571
TI  - Targeted deep sequencing reveals high diversity and variable dominance of bloom
      forming cyanobacteria in eutrophic lakes.
AB  - Cyanobacterial blooms in eutrophic lakes are severe environmental problems
      worldwide. To characterize the spatiotemporal heterogeneity of cyanobacterial
      blooms, a high-throughput method is necessary for the specific detection of
      cyanobacteria. In this study, the cyanobacterial composition of three eutrophic
      waters in China (Taihu Lake, Dongqian Lake, and Dongzhen Reservoir) was
      determined by pyrosequencing the cpcBA intergenic spacer (cpcBA-IGS) of
      cyanobacteria. A total of 2585 OTUs were obtained from the normalized cpcBA-IGS
      sequence dataset at a distance of 0.05. The 238 most abundant OTUs contained 92%
      of the total sequences and were classified into six cyanobacterial groups. The
      water samples of Taihu Lake were dominated by Microcystis, mixed Nostocales
      species, Synechococcus, and unclassified cyanobacteria. Besides, all the samples
      from Taihu Lake were clustered together in the dendrogram based on shared
      abundant OTUs. The cyanobacterial diversity in Dongqian Lake was dramatically
      decreased after sediment dredging and Synechococcus became exclusively dominant
      in this lake. The genus Synechococcus was also dominant in the surface water of
      Dongzhen Reservoir, while phylogenetically diverse cyanobacteria coexisted at a
      depth of 10m in this reservoir. In summary, targeted deep sequencing based on
      cpcBA-IGS revealed a large diversity of bloom-forming cyanobacteria in eutrophic
      lakes and spatiotemporal changes in the composition of cyanobacterial
      communities. The genus Microcystis was the most abundant bloom-forming
      cyanobacteria in eutrophic lakes, while Synechococcus could be exclusively
      dominant under appropriate environmental conditions.

PMID- 28427572
TI  - A search for mixotrophy and mucus trap production in Alexandrium spp. and the
      dynamics of mucus trap formation in Alexandrium pseudogonyaulax.
AB  - Recently, a hitherto unknown feeding strategy, the toxic mucus trap, was
      discovered in the dinoflagellate Alexandrium pseudogonyaulax. In this study, over
      40 strains of 8 different Alexandrium species (A. ostenfeldii, A. tamarense, A.
      catenella, A. taylorii, A. margalefii, A. hiranoi, A. insuetum and A.
      pseudogonyaulax) were screened for their ability to ingest prey and/or to form
      mucus traps. The mucus trap feeding strategy, where a mucus trap is towed by the
      longitudinal flagellum remains unique to A. pseudogonyaulax. In additional
      experiments, details of the trap were examined and quantified, such as speed and
      frequency of trap formation as well as what happens to the trap after the A.
      pseudogonyaulax cell detaches from it. The percentage of A. pseudogonyaulax cells
      producing a mucus trap and the number of prey cells caught increased with
      increasing prey concentration, whereas the physical size of the traps was
      independent of prey concentration. In one strain given an excess of prey, within
      1h over 90% of individual A. pseudogonyaulax cells had formed a trap, each
      containing an average of 45 prey cells. Individual A. pseudogonyaulax cells
      steadily produced traps and up to 5 traps were produced by a single A.
      pseudogonyaulax cell after only 24h. The attachment of an A. pseudogonyaulax cell
      to the trap only ceased during, and just following, cell division. Prey cells
      were, to some extent, capable of escaping from the mucus trap, but the trap
      remained sticky and continued catching prey for up to 48h after the trap had been
      abandoned by the A. pseudogonyaulax cell. These results reveal that the effects
      of the mucus trap extend far beyond the removal of prey through ingestion, and
      the potential impact of this strategy on surrounding cells is high.

PMID- 28427573
TI  - Spatial and temporal variations reveal the response of zooplankton to
      cyanobacteria.
AB  - The effects of cyanobacteria on zooplankton abundance, structure and diversity
      were investigated, based on a systematic study on spatial and temporal variations
      of cyanobacteria and zooplankton in Lake Taihu from 1998 to 2007. It was found
      that similar increasing trends of cyanobacteria/phytoplankton ratios were
      accompanied by different trends in biomass, composition and biodiversity of
      zooplankton in different regions of the lake; the cladocerans benefitted from the
      increase in cyanobacteria; however, rotifers and protozoans were negatively
      affected by cyanobacteria. The biomass-based biodiversity of phytoplankton and
      zooplankton was negatively affected by cyanobacteria as well, and the adverse
      effects were in proportion to the cyanobacteria/phytoplankton ratio. These
      results indicated interestingly that higher amounts of cyanobacteria do not
      necessarily reduce zooplankton biomass, as the biomass of larger zooplankton such
      as cladocerans was positively related to cyanobacteria. The findings are
      essential to understand the complex ecological effects of cyanobacteria blooms in
      lakes.

PMID- 28427574
TI  - Acute Noncardiovascular Illness in the Cardiac Intensive Care Unit.
AB  - BACKGROUND: Fifty years after the inception of the cardiac intensive care unit
      (CICU), noncardiovascular illnesses have become more prevalent and may contribute
      to morbidity and mortality. OBJECTIVES: The authors performed multivariate
      statistical analyses to determine the association of acute noncardiovascular
      illnesses with outcomes, including length of stay (LOS), mortality, and hospital
      readmission. METHODS: We studied 1,042 admissions between October 12, 2013 and
      November 28, 2014 to the CICU at the University of Virginia Health System, a
      tertiary-care academic medical center. Through systematic inspection of
      individual charts, we identified primary and secondary diagnoses, vital sign
      measurements, length of stay (LOS), hospital readmissions, and mortality.
      RESULTS: The most common primary diagnosis was acute coronary syndrome (25%),
      which consisted of both non-ST-segment elevation acute coronary syndrome (14%)
      and ST-segment elevation myocardial infarction (11%). Sepsis was the most
      frequent noncardiovascular primary diagnosis (5%), but it only occurred in 16% of
      all admissions. Acute kidney injury and acute respiratory failure each occurred
      in 30% of admissions. One-half of all admissions (n = 524; 50%) were marked by
      acute respiratory failure, acute kidney injury, or sepsis. Median LOS in the CICU
      and the hospital were 2 days (interquartile range [IQR]: 1 to 5 days) and 6 days
      (IQR: 3 to 11 days). Mortality was 7% in the CICU and 12% in the hospital. Of the
      920 patients who survived to hospital discharge, 171 (19%) were readmitted within
      30 days. Sepsis, acute kidney injury, and acute respiratory failure were
      associated with mortality. Acute kidney injury, acute respiratory failure, and
      new-onset subclinical atrial fibrillation, which occurred in 8% of admissions,
      were all associated with CICU LOS. CONCLUSIONS: Many patients in the modern CICU
      have acute noncardiovascular illnesses that are associated with mortality and
      increased LOS.

PMID- 28427575
TI  - The Evolving Medical Complexity of the Modern Cardiac Intensive Care Unit.

PMID- 28427577
TI  - Bleeding and Mortality With Dual Antiplatelet Therapy: The Rashomon Effect.

PMID- 28427576
TI  - Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy
      After Coronary Stenting.
AB  - BACKGROUND: Although some randomized controlled trials (RCTs) and meta-analyses
      have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated
      with increased mortality, the mechanistic underpinnings of this association
      remain unclear. OBJECTIVES: The aim of this study was to analyze the associations
      among bleeding, mortality, and DAPT duration after drug-eluting stent
      implantation in a meta-analysis of RCTs. METHODS: RCTs comparing different DAPT
      durations after drug-eluting stent placement were sought through the MEDLINE,
      Embase, and Cochrane databases and the proceedings of international meetings.
      Deaths were considered possibly bleeding related if occurring within 1 year of
      the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary
      analysis was performed in a modified intention-to-treat population in which
      events occurring when all patients were on DAPT were excluded. RESULTS:
      Individual patient data were obtained for 6 RCTs, and aggregate data were
      available for 12 RCTs. Patients with bleeding had significantly higher rates of
      mortality compared with those without, and in a time-adjusted multivariate
      analysis, bleeding was an independent predictor of mortality occurring within 1
      year of the bleeding episode (hazard ratio: 6.93; 95% confidence interval: 4.53
      to 10.60; p < 0.0001). Shorter DAPT was associated with lower rates of all-cause
      death compared with longer DAPT (hazard ratio: 0.85; 95% confidence interval:
      0.73 to 1.00; p = 0.05), which was driven by lower rates of bleeding-related
      deaths with shorter DAPT compared with prolonged DAPT (hazard ratio: 0.65; 95%
      confidence interval: 0.43 to 0.99; p = 0.04). Mortality unrelated to bleeding was
      comparable between the 2 groups. Similar results were apparent in the modified
      intention-to-treat population. CONCLUSIONS: Bleeding was strongly associated with
      the occurrence of mortality within 1 year after the bleeding event. Shorter
      compared with longer DAPT was associated with lower risk for bleeding-related
      death, a finding that may underlie the lower all-cause mortality with shorter
      DAPT in the RCTs of different DAPT durations after DES.

PMID- 28427578
TI  - Implantable Cardioverter-Defibrillators With Versus Without Resynchronization
      Therapy in Patients With a QRS Duration >180 ms.
AB  - BACKGROUND: More than 20% of Medicare beneficiaries receiving cardiac
      resynchronization therapy defibrillators (CRT-D) have a very wide (>=180 ms) QRS
      complex duration (QRSD). Outcomes of CRT-D in these patients are not well
      established because they have been underrepresented in clinical trials.
      OBJECTIVES: This study examined outcomes in patients with CRT-D in a very wide
      QRSD with left bundle branch block (LBBB) versus those without LBBB. METHODS:
      Medicare patients from the Implantable Cardioverter Defibrillator Registry
      (January 1, 2005, through April 30, 2006) with a CRT-D and confirmed Class I or
      IIa indications for CRT-D were matched to implantable cardioverter-defibrillator
      (ICD) patients without CRT despite having Class I or IIa indications for CRT.
      Mortality and heart failure hospitalizations longer than 4 years with CRT-D
      versus standard ICDs based on a QRSD and morphology were analyzed. RESULTS: We
      analyzed 24,960 patients. Among those with LBBB, patients with a QRSD >=180 ms
      had a greater adjusted survival benefit with CRT-D versus standard ICD (hazard
      ration [HR] for death: 0.65; 95% confidence interval [CI]: 0.59 to 0.72) compared
      with those having a QRSD 120 to 149 ms (HR: 0.85; 95% CI: 0.80 to 0.92) and 150
      to 179 ms (HR: 0.87; 95% CI: 0.81 to 0.93). CRT-D versus ICD was associated with
      an improvement in survival in those with LBBB and a QRSD >=180 ms (adjusted HR
      for death: 0.78; 95% CI: 0.68 to 0.91), but not in those with LBBB and a QRSD 150
      to 179 ms (adjusted HR for death: 1.06; 95% CI: 0.95 to 1.19). CONCLUSIONS:
      Improvements in both survival and heart failure hospitalizations with CRT-D were
      greatest in patients with a QRSD >=180 ms with or without LBBB, whereas patients
      with a QRSD 150 to 179 ms without LBBB had no improvement in survival with CRT-D,
      and those with a QRSD 150 to 179 ms and LBBB had only a modest improvement.

PMID- 28427579
TI  - Very Wide QRS Complex (>=180 ms) and CRT Efficacy.

PMID- 28427581
TI  - CABG Versus PCI for Complex Coronary Disease: Time to Close the Books.

PMID- 28427580
TI  - Quality of Life After Surgery or DES in Patients With 3-Vessel or Left Main
      Disease.
AB  - BACKGROUND: In the SYNTAX (Synergy Between Percutaneous Coronary Intervention
      With Taxus and Cardiac Surgery) trial, patients with 3-vessel or left main
      coronary artery disease (CAD) had improved long-term outcomes with coronary
      artery bypass graft (CABG) surgery compared with percutaneous coronary
      intervention (PCI) with drug-eluting stents (DES), improvements driven mainly by
      differences in myocardial infarction and repeat revascularization. OBJECTIVES:
      This study compared the long-term quality-of-life benefits of DES-PCI versus CABG
      for patients with 3-vessel or left main CAD. METHODS: Between 2005 and 2007, the
      SYNTAX trial randomized 1,800 patients with 3-vessel or left main CAD to either
      CABG or DES-PCI. Health status was assessed at baseline and at 1, 6, 12, 36, and
      60 months by using the Seattle Angina Questionnaire (SAQ) and the 36-Item Short
      Form Health Survey. RESULTS: At 5-year follow-up, CABG was superior to DES-PCI on
      several SAQ domains including angina frequency and physical function, as well as
      the role physical and role emotional scales of the 36-Item Short Form Health
      Survey. Subgroup analysis demonstrated a significant interaction between
      angiographic complexity (as assessed by the SYNTAX score) and angina relief (mean
      difference in the SAQ angina frequency score for CABG vs. PCI of -0.9, 3.3, and
      3.9 points for low, intermediate, and high SYNTAX score patients, respectively; p
      = 0.048 for interaction). CONCLUSIONS: Among patients with 3-vessel or left main
      CAD, both CABG and DES-PCI were associated with substantial and sustained quality
      of-life benefits over 5 years of follow-up. In general, CABG resulted in greater
      angina relief, although the absolute treatment benefit was small. Angina relief
      at 5 years was enhanced with CABG among patients with high SYNTAX scores, a
      finding reinforcing the recommendation that CABG should be strongly preferred for
      such patients. (Synergy Between Percutaneous Coronary Intervention With Taxus and
      Cardiac Surgery [SYNTAX]; NCT00114972).

PMID- 28427584
TI  - Impact of Aortic Valve Calcification and Sex on Hemodynamic Progression and
      Clinical Outcomes in AS.

PMID- 28427585
TI  - Ticagrelor Versus Clopidogrel on Myocardial Infarct Size in Patients Undergoing
      Primary Percutaneous Coronary Intervention.

PMID- 28427586
TI  - The Complex miRNAs-p53 Signaling Network in Cardiovascular Disease.

PMID- 28427582
TI  - Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in
      Surgical Prosthesis: An Expert Statement.
AB  - The VARC (Valve Academic Research Consortium) for transcatheter aortic valve
      replacement set the standard for selecting appropriate clinical endpoints
      reflecting safety and effectiveness of transcatheter devices, and defining single
      and composite clinical endpoints for clinical trials. No such standardization
      exists for circumferentially sutured surgical valve paravalvular leak (PVL)
      closure. This document seeks to provide core principles, appropriate clinical
      endpoints, and endpoint definitions to be used in clinical trials of PVL closure
      devices. The PVL Academic Research Consortium met to review evidence and make
      recommendations for assessment of disease severity, data collection, and updated
      endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in
      concordance with VARC recommendations. Unresolved issues in the field are
      outlined. The current PVL Academic Research Consortium provides recommendations
      for assessment of disease severity, data collection, and endpoint definitions.
      Future research in the field is warranted.

PMID- 28427587
TI  - Reply: The Complex miRNAs-p53 Signaling Network in Cardiovascular Disease.

PMID- 28427583
TI  - Improving Atrial Fibrillation Therapy: Is There a Gene for That?
AB  - Atrial fibrillation (AF) is an all-too-common and often challenging reality of
      clinical care. AF leads to significant morbidity and mortality; however,
      currently available treatments for AF have modest efficacy and high recurrence
      rates. In recent years, genetic therapy approaches have been explored in
      preclinical models of AF, and offer potential as a treatment modality with
      targeted delivery, tissue specificity, and therapy tailored to address mechanisms
      underlying the arrhythmia. However, many challenges remain before gene therapy
      can advance to a clinically relevant AF treatment. In this review, we summarize
      the available published data on gene therapy and discuss the challenges,
      opportunities, and limitations of this approach.

PMID- 28427588
TI  - Deep Learning With Unsupervised Feature in Echocardiographic Imaging.

PMID- 28427589
TI  - Reply: Deep Learning With Unsupervised Feature in Echocardiographic Imaging.

PMID- 28427590
TI  - Correction.

PMID- 28427591
TI  - Correction.

PMID- 28427592
TI  - Pathologic Active mTOR Mutation in Brain Malformation with Intractable Epilepsy
      Leads to Cell-Autonomous Migration Delay.
AB  - The activation of phosphatidylinositol 3-kinase-AKTs-mammalian target of
      rapamycin cell signaling pathway leads to cell overgrowth and abnormal migration
      and results in various types of cortical malformations, such as
      hemimegalencephaly (HME), focal cortical dysplasia, and tuberous sclerosis
      complex. However, the pathomechanism underlying abnormal cell migration remains
      unknown. With the use of fetal mouse brain, we performed causative gene analysis
      of the resected brain tissues from a patient with HME and investigated the
      pathogenesis. We obtained a novel somatic mutation of the MTOR gene, having
      approximately 11% and 7% mutation frequency in the resected brain tissues.
      Moreover, we revealed that the MTOR mutation resulted in hyperphosphorylation of
      its downstream molecules, S6 and 4E-binding protein 1, and delayed cell migration
      on the radial glial fiber and did not affect other cells. We suspect cell
      autonomous migration arrest on the radial glial foot by the active MTOR mutation
      and offer potential explanations for why this may lead to cortical malformations
      such as HME.

PMID- 28427593
TI  - Economic Outcomes of Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting
      Stents in Patients Undergoing Percutaneous Coronary Intervention: 1-Year Results
      From the ABSORB III Trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the economic impact of the
      Absorb bioresorbable vascular scaffold compared with the Xience everolimus
      eluting stent in patients undergoing percutaneous coronary intervention.
      BACKGROUND: The ABSORB III trial (Everolimus-Eluting Bioresorbable Scaffolds for
      Coronary Artery Disease) demonstrated that the Absorb scaffold was noninferior to
      the Xience stent with respect to target lesion failure at 1 year. Whether health
      care costs differ between the Absorb scaffold and the Xience stent is unknown.
      METHODS: We performed a prospective health economic study alongside the ABSORB
      III trial, in which patients undergoing percutaneous coronary intervention for
      stable or unstable angina were randomized to receive the Absorb scaffold (n =
      1,322) or Xience stent (n = 686). Resource use data were collected through 1 year
      of follow-up. Costs were assessed using resource-based accounting (for
      procedures), MedPAR data (for other index hospitalization costs), and Medicare
      reimbursements (for follow-up costs and physician fees). RESULTS: Initial
      procedural costs were higher with the Absorb scaffold than the Xience stent
      ($6,316 +/- 1,892 vs. $6,103 +/- 1,895; p = 0.02), driven mainly by greater
      balloon catheter use and the higher cost of the scaffold in the Absorb group.
      Nonetheless, index hospitalization costs ($15,035 +/- 2,992 for Absorb vs.
      $14,903 +/- 3,449 for Xience; p = 0.37) and total 1-year costs ($17,848 +/- 6,110
      for Absorb vs. $17,498 +/- 7,411 for Xience; p = 0.29) were similar between the 2
      groups. CONCLUSIONS: Although initial procedural costs were higher with the
      Absorb scaffold, there were no differences in total 1-year health care costs
      between the 2 cohorts. Longer term follow-up is needed to determine whether
      meaningful cost savings emerge after scaffold resorption. (A Clinical Evaluation
      of AbsorbTM BVS, the Everolimus-Eluting Bioresorbable Vascular Scaffold in the
      Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT01751906).

PMID- 28427594
TI  - The Bioresorbable Drug-Eluting Coronary Stent: The Price Is Right?

PMID- 28427596
TI  - Bioresorbable Vascular Scaffolds: A Step Closer to the Dream?

PMID- 28427595
TI  - Vasomotor Response to Nitroglycerine Over 5 Years Follow-Up After Everolimus
      Eluting Bioresorbable Scaffold Implantation.
AB  - OBJECTIVES: This study investigated the vasomotor response to nitroglycerine
      (NTG) up to 5 years after ABSORB implantation. BACKGROUND: There are no data
      regarding long-term vasomotor response after everolimus-eluting bioresorbable
      vascular scaffold ABSORB implantation. METHODS: We performed quantitative
      coronary angiography of the scaffolded and proximal and distal adjacent segments
      of patients from ABSORB Cohort B study before and after 200 MUg of intracoronary
      NTG at 2, 3, and 5 years of follow-up. The mean changes of maximal and mean lumen
      diameters in the scaffolded and adjacent segments were calculated. RESULTS: The
      mean in-scaffold lumen diameter change in response to NTG showed a trend to
      increase over time with absolute values of 0.03 +/- 0.09 mm, 0.05 +/- 0.12 mm,
      and 0.07 +/- 0.08 mm at 2, 3, and 5 years, respectively (p = 0.40). The maximal
      in-scaffold lumen diameter change significantly increased with values of 0.03 +/-
      0.14 mm, 0.06 +/- 0.16 mm, and 0.11 +/- 0.1 mm at 2, 3, and 5 years, respectively
      (p = 0.03). The normalized mean lumen diameter change after NTG in the scaffold
      relative to the adjacent segments was 51.9 +/- 54.8% at 5 years of follow-up (p =
      0.60). CONCLUSIONS: Although there was a numerical increase of the vasomotor
      response to NTG after ABSORB implantation measured by quantitative coronary
      angiography with mean lumen diameter, the change was not statistically
      significant. However, the maximal lumen diameter changes increased over time from
      2 to 5 years and attained statistical significance. The vasomotor response to NTG
      after ABSORB implantation moderately trended to increase, which is consistent
      with the progressive degradation and bioresorption of the scaffold, but the
      degree of vasomotor response remained lower in comparison with adjacent segments.

PMID- 28427599
TI  - Toward Precision in Balloon-Expandable TAVR: Oversizing Tight Versus Just Right.

PMID- 28427597
TI  - Intentional Percutaneous Laceration of the Anterior Mitral Leaflet to Prevent
      Outflow Obstruction During Transcatheter Mitral Valve Replacement: First-in-Human
      Experience.
AB  - OBJECTIVES: This study sought to use a new catheter technique to split the
      anterior mitral valve leaflet (AML) and prevent iatrogenic left ventricular
      outflow tract (LVOT) obstruction immediately before transcatheter mitral valve
      replacement (TMVR). BACKGROUND: LVOT obstruction is a life-threatening
      complication of TMVR, caused by septal displacement of the AML. METHODS: The
      procedure was used in patients with severe mitral valve disease and prohibitive
      surgical risk. Patients either had prior surgical mitral valve ring (n = 3) or
      band annuloplasty (n = 1) or mitral annular calcification with stenosis (n = 1).
      Iatrogenic LVOT obstruction or transcatheter heart valve dysfunction was
      predicted in all based on echocardiography and computed tomography. Transfemoral
      coronary guiding catheters directed an electrified guidewire across the center
      and base of the AML toward a snare in the left atrium. The externalized guidewire
      loop was then electrified to lacerate the AML along the centerline from base to
      tip, sparing chordae, immediately before transseptal TMVR. RESULTS: Five patients
      with prohibitive risk of LVOT obstruction or transcatheter heart valve
      dysfunction from TMVR successfully underwent LAMPOON, with longitudinal splitting
      of the A2 scallop of the AML, before valve implantation. Multiplane computed
      tomography modeling predicted hemodynamic collapse from TMVR assuming an intact
      AML. However, critical LVOT gradients were not seen following LAMPOON and TMVR.
      Doppler blood flow was seen across transcatheter heart valve struts that
      encroached the LVOT, because the AML was split. Transcatheter heart valve
      function was unimpeded. CONCLUSIONS: This novel catheter technique, which
      resembles surgical chord-sparing AML resection, may enable TMVR in patients with
      prohibitive risk of LVOT obstruction or transcatheter heart valve dysfunction.

PMID- 28427601
TI  - Blurred Lines: Assessing the Stent as Provocateur in Carotid Intervention.

PMID- 28427598
TI  - Computed Tomography-Based Oversizing Degrees and Incidence of Paravalvular
      Regurgitation of a New Generation Transcatheter Heart Valve.
AB  - OBJECTIVES: The aim of the study was to investigate the influence of the extent
      of computed tomography (CT)-based area and perimeter oversizing on the incidence
      and severity of paravalvular aortic regurgitation (PAR) for the Edwards SAPIEN 3
      (Edwards Lifesciences, Irvine, California) device, using CT data and
      echocardiographic outcome data of the PARTNER II (Placement of AoRTic
      TraNscathetER Valves Trial II) SAPIEN 3 intermediate-risk cohort. BACKGROUND:
      Transcatheter heart valve (THV) sizing algorithms are device specific, requiring
      refinements for new valve designs. METHODS: A total of 835 intermediate-risk
      patients with severe, symptomatic aortic stenosis enrolled in a multicenter,
      nonrandomized registry at 57 sites in the United States and Canada with available
      systolic CT data and echocardiographic follow-up were included in this analysis.
      THV size selection was primarily CT guided based on annular area. Area-based and
      perimeter-based oversizing was calculated using systolic annular CT dimensions
      and nominal dimensions of the implanted THV size. PAR was assessed at 30 days
      according to a 5-class scheme. RESULTS: Mean oversizing by area was 7.7 +/- 9.4%
      and mean oversizing by perimeter was 1.7 +/- 4.4%. An inverse proportional
      relationship between degree of oversizing and frequency and severity of PAR was
      observed for both area and perimeter oversizing. Perimeter and area oversizing
      confer similar predictive capacity in regard to the occurrence of PAR after THV
      implantation (area under the curve: 0.78 [95% confidence interval: 0.70 to 0.85]
      vs. area under the curve: 0.78 [95% confidence interval: 0.72 to 0.85]; p <
      0.0001). No aortic root ruptures were observed. CONCLUSIONS: For the SAPIEN 3
      THV, the frequency and extent of PAR is inversely related to the degree of
      oversizing with acceptable rates of PAR being achieved at lower degrees of
      oversizing. Perimeter and area oversizing confer similar predictive capacity in
      regard to the occurrence of PAR after implantation of the SAPIEN 3 THV.
      Therefore, the SAPIEN 3 THV may offer the opportunity to reduce the risk of
      annular rupture associated with more significant degrees of oversizing in
      borderline annular anatomy. (The PARTNER II Trial: Placement of AoRTic
      TraNscathetER Valves [PARTNER II]; NCT01314313).

PMID- 28427600
TI  - Carotid Artery Stenting: Investigation of Plaque Protrusion Incidence and
      Prognosis.
AB  - OBJECTIVES: This study sought to clarify the incidence and prognosis of PP in
      carotid artery stenting (CAS). BACKGROUND: Projections thought to be plaque may
      be observed inside the stent on angiography or intravascular ultrasound (IVUS)
      during CAS. Known as plaque protrusion (PP), the incidence and prognosis of this
      complication are unclear. METHODS: A total of 354 consecutive carotid
      atherosclerotic stenoses in 328 patients (285 men, 43 women; age range 51 to 97
      years [mean age 73.6 years]; 158 symptomatic cases; stenosis rate, 50% to 99%
      [mean 81.0%]) who underwent CAS under IVUS between October 2007 and March 2016
      were retrospectively analyzed. PP was defined as plaque seen inside the stent
      lumen on both digital subtraction angiography and IVUS. The incidence and
      prognosis (rate of stroke within 30 post-operative days) of PP and the rate of
      ischemic lesions on the treated side on diffusion-weighted imaging performed
      within 48 post-operative hours within the PP group were investigated. RESULTS: PP
      was observed in 9 cases (2.6%). Ischemic stroke occurred in 6 of 9 PP cases
      (66.7%; 1 major, 5 minor). Ischemic lesions were observed on diffusion-weighted
      imaging in 8 of 9 cases (88.9%). PP was strongly associated with perioperative
      ischemic stroke. A significant increase in PP susceptibility was observed with
      open-cell stent use and unstable plaque. CONCLUSIONS: The incidence of PP in CAS
      was 2.6%, with a high risk of ischemic complications if PP was observed. The
      present findings indicate the necessity of appropriate device selection to avoid
      PP.

PMID- 28427602
TI  - Methodological Issues and Their Impact on Conclusions.

PMID- 28427603
TI  - Ventricular Unloading in Porcine Models.

PMID- 28427604
TI  - Reply: Weil's Response.

PMID- 28427605
TI  - Impella Retrieval: Redux.

PMID- 28427606
TI  - Angiographic Follow-Up in Patients With Coronary Artery Disease: Is There a
      Window to Be Definitively Closed?

PMID- 28427607
TI  - Reply: Angiographic Follow-Up in Patients With Coronary Artery Disease: Is There
      a Window to Be Definitively Closed?

PMID- 28427608
TI  - Advise and Consent.

PMID- 28427609
TI  - Special section on psychological aspects of cancer: Patient and clinician
      perspectives.

PMID- 28427610
TI  - The trauma chain of survival - Each link is equally important (but some links are
      more equal than others).

PMID- 28427611
TI  - Experimental study on the influence of low-frequency and low-intensity ultrasound
      on the permeability of the Mycobacterium smegmatis cytoderm and potentiation with
      levofloxacin.
AB  - Tuberculosis is an infectious disease caused by the bacterium M. tuberculosis.
      The aim of this study was to investigate the bactericidal effect and underlying
      mechanisms of low-frequency and low-intensity ultrasound combined with
      levofloxacin treatment against M. smegmatis (a surrogate of M. tuberculosis). As
      part of this study, M. smegmatis was continuously irradiated with low frequency
      ultrasound (42kHz) using several different doses whereby both intensity (0.138,
      0.190 and 0.329W/cm2) and exposure time (5, 15 and 20min) were varied. Flow
      cytometric analyses revealed that the permeability of M. smegmatis increased
      following ultrasound exposure. The survival rate, structure and morphology of
      bacteria in the lower-dose (ISATA=0.138W/cm2 for 5min) ultrasound group displayed
      no significant differences upon comparison with the untreated group. However, the
      survival rate of bacteria was significantly reduced and the bacterial structure
      was damaged in the higher-dose (ISATA=0.329W/cm2 for 20min) ultrasound group.
      Ultrasound irradiation (0.138W/cm2) was subsequently applied to M. smegmatis in
      combination with levofloxacin treatment for 5min. The results demonstrated that
      the bactericidal effect of ultrasonic irradiation combined with levofloxacin is
      higher compared to ultrasound alone or levofloxacin alone.

PMID- 28427612
TI  - Study of ultrasonic cavitation during extraction of the peanut oil at varying
      frequencies.
AB  - The ultrasonic extraction of oils is a typical physical processing technology.
      The extraction process was monitored from the standpoint of the oil quality and
      efficiency of oil extraction. In this study, the ultrasonic cavitation fields
      were measured by polyvinylidene fluoride (PVDF) sensor. Waveform of ultrasonic
      cavitation fields was gained and analyzed. The extraction yield and oxidation
      properties were compared. The relationship between the fields and cavitation
      oxidation was established. Numerical calculation of oscillation cycle was done
      for the cavitation bubbles. Results showed that the resonance frequency, fr, of
      the oil extraction was 40kHz. At fr, the voltage amplitude was the highest; the
      time was the shortest as reaching the amplitude of the waveform. Accordingly, the
      cavitation effect worked most rapidly, resulting in the strongest cavitation
      intensity. The extraction yield and oxidation properties were closely related to
      the cavitation effect. It controlled the cavitation oxidation effectively from
      the viewpoint of chemical and physical aspects.

PMID- 28427613
TI  - Disinfection effect of a continuous-flow ultrasound/ultraviolet baffled reactor
      at a pilot scale.
AB  - An ultrasound/ultraviolet (US/UV) baffled reactor was developed to fill the gap
      in ultraviolet (UV) disinfection associated with disinfection efficiency.
      According to the previously selected operational condition, a continuous-flow
      US/UV baffled reactor was continuously operated in a wastewater treatment plant
      at a pilot scale for nearly three months, and the disinfection influent and
      effluent were analyzed, including fecal coliforms, Escherichia coli, and fecal
      streptococci. The US/UV baffled reactor could guarantee a high effluent
      disinfection performance in terms of fecal coliforms removal even with the
      fluctuation of the secondary effluent. All the disinfected effluents satisfied
      the requirement of the "Pollutants Discharge Standard of Municipal Wastewater
      Treatment Plant in China" (fecal coliforms below 1000CFU/L for class 1A), and 87%
      of the tested fecal coliforms concentration in the disinfected effluent was below
      100CFU/L, nearly eliminating all fecal coliforms. Further analysis of the E. coli
      and fecal streptococci showed the broad disinfection ability and high
      disinfection efficiency of the US/UV baffled reactor. The flexibility of the
      specific energy consumption for the disinfection system depends on the water
      quality.

PMID- 28427614
TI  - Production of graphene quantum dots by ultrasound-assisted exfoliation in
      supercritical CO2/H2O medium.
AB  - In this research, three kinds of graphene quantum dots (GQDs)-pristine graphene
      quantum dots (PGQDs), expanded graphene quantum dots (EGQDs) and graphene oxide
      quantum dots (GOQDs)-were produced from natural graphite, expanded graphite, and
      oxide graphite respectively in an ultrasound-assisted supercritical CO2
      (scCO2)/H2O system. The effects of aqueous solution content ratio, system
      pressure, and ultrasonic power on the yields of different kinds of GQDs were
      investigated. According to these experiment results, the combination of the
      intense knocking force generated from high-pressure acoustic cavitation in a
      scCO2/H2O system and the superior penetration ability of scCO2 was considered to
      be the key to the successful exfoliation of such tiny pieces from bulk graphite.
      An interesting result was found that, contrary to common experience, the yield of
      PGQDs from natural graphite was much higher than that of GOQDs from graphite
      oxide. Based on the experimental analysis, the larger interlayer resistance of
      natural graphite, which hindered the insertion of scCO2 molecules, and the
      hydrophobic property of natural graphite surface, which made the planar more
      susceptible to the attack of ultrasonic collapsing bubbles, were deduced to be
      the two main reasons for this result. The differences in characteristics among
      the three kinds of GQDs were also studied and compared in this research. In our
      opinion, this low-cost and time-saving method may provide an alternative green
      route for the production of various kinds of GQDs, especially PGQDs.

PMID- 28427615
TI  - Utilization of ultrasonic irradiation as a green and effective strategy to
      prepare poly(N-vinyl-2-pyrrolidone)/modified nano-copper (II) oxide
      nanocomposites.
AB  - The present paper describes the result of investigations into preparation of
      novel nanocomposites (NCs) based on poly(N-vinyl-2-pyrrolidone) (PVP) as a
      biocompatible polymer and modified copper (II) oxide nanoparticles (NPs) as a
      nano-filler. To achieve optimum NCs properties, different ratios of modified
      copper (II) oxide NPs (3, 5, and 7wt%) were used to fabricate PVP NCs and also
      the ultrasonic irradiation was utilized to perform these processes as a fast and
      effective method. Subsequently, the structure of the obtained nanohybrids was
      characterized by various techniques. The suitable incorporation between PVP
      matrix and modified CuO NPs can be seen from the FT-IR spectra. The obtained NCs
      indicated an efficient thermal improvement in comparison to the pristine polymer.
      Also, the uniform dispersion of modified CuO NPs in the PVP matrix was detected
      by FE-SEM and EDX. According to UV absorption spectra, it is clear that these NCs
      can be used in UV protecting applications.

PMID- 28427616
TI  - Intensification of biodiesel production using dual-frequency counter-current
      pulsed ultrasound.
AB  - Biodiesel production from soybean oil deodorizer distillate intensified by dual
      frequency counter-current pulsed ultrasound and the kinetics were studied.
      Results indicated that the biodiesel conversions enhanced by single-frequency
      were lower than those enhanced by dual-frequency. For dual-frequency, the
      biodiesel conversion of SMM was higher than those of SQM. The biodiesel
      conversion of the combination of 20/28kHz is the highest. The effects of 20/28kHz
      SMM on biodiesel production were studied and optimal conditions were: methanol to
      triglyceride molar ratio 8:1, catalyst content 1.8%, the water content in
      feedstock should be less than 0.4%, the acid value of feedstock should be less
      than 2mgKOH.g-1, the biodiesel conversion could reach 96.3%. The kinetics of SMM
      and SSPU were studied and results showed that the transesterification reaction
      was pseudo-second order and the energy activation obtained by SMM and SSPU were
      18.122kJ.mol-1 and 26.034kJ.mol-1, respectively. These results showed that
      transesterification reaction intensified by SMM is easier to take place than
      SSPU.

PMID- 28427617
TI  - Effects of ultrasound on microbial growth and enzyme activity.
AB  - Nowadays, ultrasound is widely used in many aspects. In the last few years, many
      papers have concentrated on the applications of ultrasound in engineering,
      chemistry, medicine, physics and biology, but few in biological effects such as
      the acceleration effects on proliferation of microbial cells, the inactivation
      effects on microorganisms and the influences on the activities of enzyme. Thus,
      the objective of this review is to investigate the biological effects of
      ultrasound on these aspects.

PMID- 28427618
TI  - Effects of high intensity unltrasound on structural and physicochemical
      properties of myosin from silver carp.
AB  - Myosin from silver carp was sonicated with varying power output (100, 150, 200
      and 250W) for 3, 6, 9, and 12min. The changes in the structure and
      physicochemical properties of myosin were evaluated by dynamic light scattering,
      SDS-PAGE and some physicochemical indexes. The ultrasound treatments induced a
      significant conversion of myosin aggregates to smaller ones with a more uniform
      distribution, and obvious enhancement in solubility. The structure of myosin was
      also notably changed by sonication, with a decrease in Ca2+-ATPase activity and
      SH content, and an increase in surface hydrophobicity. Furthermore, SH groups
      were oxidized, leading to a decrease in reactive SH and total SH contents. SDS
      PAGE analysis revealed that ultrasound could induce the degradation of myosin
      heavy chain and change the protein fraction of myosin. Collectively, the
      ultrasonic treatment of 100W for 3min showed slight influence on the SH content,
      S0-ANS, and electrophoretic patterns, and the extent of changes in myosin
      structure and physicochemical properties tended to increase with ultrasonic power
      and time. The integrated data indicate that ultrasonic treatment can facilitate
      the improvement of the solubility and dispersion of myosin, but the choice of a
      suitable ultrasonic condition to avoid oxidation and degradation of myosin is
      very important.

PMID- 28427619
TI  - Application of sonochemical technique for sustainable surface modification of
      polyester fibers resulting in durable nano-sonofinishing.
AB  - In this study firstly we aimed at introducing the effects of ultrasound and
      sonochemistry in surface modification of polyester fibers. For this purpose,
      surface modification of polyester fibers was achieved by ultrasound, and contact
      angle and water spreading time measurements were used to confirm the treatment
      efficiency. Hydroxylation of terephthalate was occurred by hydroxyl radicals
      formed during water sonolysis, forming functional groups on polyester surface, as
      confirmed by XPS analysis, improving the wettability. Creation of hydroxyl groups
      under sono surface modification was further assessed by dyeing the samples with
      reactive dye. Secondly, we investigated the durable nano-sono-finishing of
      polyester fibers by nano TiO2 particles under ultrasonic bath. Washing durability
      of the sono-synthesized TiO2 nanoparticles was evaluated confirming the effective
      role of sonochemical technique in polyester surface modification. Thirdly, the
      self-cleaning activity of sono-synthesized nano TiO2 treated samples toward
      degradation of Methylene Blue stain was superior to coating of fabric with
      commercial nano TiO2 using identical procedure.

PMID- 28427620
TI  - Effect of ultrasonic frequency on size distributions of nanosized mist generated
      by ultrasonic atomization.
AB  - Ultrasonic atomization is used to produce fine liquid mists with diameter ranges
      below 100nm. We investigated the effect of the frequency on the size distribution
      of ultrasonic mist. A bimodal distribution was obtained for the mist generated by
      ultrasonic atomization with a wide-range particle spectrometer. The peak diameter
      decreased with increasing frequency, and the number concentration of the mist
      increased in the smaller range. We determined the relation between the size
      distribution of the mist and the ultrasonic frequency, and we proposed a
      generation mechanism for the ultrasonic nanosized mist based on the amount of
      water vapor around the liquid column. Increasing the power intensity and density
      by changing the surface diameter of the ultrasonic oscillator affected the number
      concentration and size distribution of the nanosized mist. Using this technique,
      the diameter of the mist can be controlled by changing the frequency of the
      ultrasonic transducer.

PMID- 28427621
TI  - Engineering design and prototype development of a full scale ultrasound system
      for virgin olive oil by means of numerical and experimental analysis.
AB  - The aim of the virgin olive oil extraction process is mainly to obtain the best
      quality oil from fruits, by only applying mechanical actions while guaranteeing
      the highest overall efficiency. Currently, the mechanical methods used to extract
      virgin oils from olives are basically of two types: the discontinuous system
      (obsolete) and the continuous one. Anyway the system defined as "continuous" is
      composed of several steps which are not all completely continuous, due to the
      presence of the malaxer, a device that works in batch. The aim of the paper was
      to design, realize and test the first full scale sono-exchanger for the virgin
      olive oil industry, to be placed immediately after the crusher and before the
      malaxer. The innovative device is mainly composed of a triple concentric pipe
      heat exchanger combined with three ultrasound probes. This mechanical solution
      allows both the cell walls (which release the oil droplets) along with the minor
      compounds to be destroyed more effectively and the heat exchange between the
      olive paste and the process water to be accelerated. This strategy represents the
      first step towards the transformation of the malaxing step from a batch operation
      into a real continuous process, thus improving the working capacity of the
      industrial plants. Considering the heterogeneity of the olive paste, which is
      composed of different tissues, the design of the sono-exchanger required a
      thorough fluid dynamic analysis. The thermal effects of the sono-exchanger were
      monitored by measuring the temperature of the product at the inlet and the outlet
      of the device; in addition, the measurement of the pigments concentration in the
      product allowed monitoring the mechanical effects of the sono-exchanger. The
      effects of the innovative process were also evaluated in terms of extra virgin
      olive oil yields and quality, evaluating the main legal parameters, the
      polyphenol and tocopherol content. Moreover, the activity of the polyphenol
      oxidase enzyme in the olive paste was measured.

PMID- 28427622
TI  - Efficient removal of crystal violet and methylene blue from wastewater by
      ultrasound nanoparticles Cu-MOF in comparison with mechanosynthesis method.
AB  - The present investigation reports the synthesis of CuBTC (BTC=1,3,5
      benzenetricarboxylate) metal-organic frameworks (MOFs) under solid-state
      conditions and ultrasound irradiation. Herein, we study uptake and release
      properties of crystal violet (CV) and methylene blue (MB) from ultrasound nano
      CuBTC MOF in comparison with mechanosynthesis method (bulk structure). The
      ultrasound-assisted methods give a decrease in the surface area as calculated
      from the reduced nitrogen adsorption capability. In comparison, the uptake of
      guest molecules on ultrasound nano-CuBTC is remarkable and clearly exceeds that
      of bulk structure in the aqueous solution of guests. In bulk compound the channel
      length is increased so that the amount of adsorption is decreased a little. The
      small guest enters and leaves the cavity rapidly, whereas larger guests enter
      slowly due to their size relative to the size of the gaps in the capsule. As a
      result, the uptake and release of MB from CuBTC is faster than that of CV.

PMID- 28427623
TI  - Degradation of reactive blue 13 using hydrodynamic cavitation: Effect of
      geometrical parameters and different oxidizing additives.
AB  - Decolorization of reactive blue 13 (RB13), a sulphonated azo dye, was
      investigated using hydrodynamic cavitation (HC). The aim of research article is
      to check the influence of geometrical parameters (total flow area, the ratio of
      throat perimeter to its cross-sectional area, throat shape and size, etc.) and
      configuration of the cavitating devices on decolorization of RB13 in aqueous
      solution. For this purpose, eight cavitating devices i.e. Circular and slit
      venturi, and six orifice plates having different flow area and perimeter were
      used in the present work. Initially, the effects of various operating parameters
      such as solution pH, initial dye concentration, operating inlet pressure and
      cavitation number on the decolorization of RB13 have been investigated, and the
      optimum operating conditions were found. Kinetic analysis revealed that the
      decolorization and mineralization of RB13 using HC followed first order reaction
      kinetics. Almost 47% decolorization of RB13 was achieved using only HC with slit
      venturi as a cavitating device at an optimum inlet pressure of 0.4MPa and pH of
      the solution as 2.0. It has been found that in case of orifice plates, higher
      decolorization rate of 4*10-3min-1 was achieved using orifice plate 2 (OP2) which
      is having higher flow area and perimeter (alpha=2.28). The effect of process
      intensifying agents (hydrogen peroxide and ferrous sulphate) and different
      gaseous additives (oxygen and ozone) on the extent of decolorization of RB13 were
      also examined. Almost 66% decolorization of RB13 was achieved using HC combined
      with 2Lmin-1 of oxygen and in combination with ferrous sulphate (1:3). Nearly 91%
      decolorization was achieved using HC combined with H2O2 at an optimum molar ratio
      (dye:H2O2) of 1:20 while almost complete decolorization was observed in 15min
      using a combination of HC and ozone at 3gh-1 ozone feed rate. Maximum 72% TOC was
      removed using HC coupled with 3gh-1 ozone feed rate.

PMID- 28427624
TI  - Ultrasound-assisted biodiesel production by a novel composite of Fe(III)-based
      MOF and phosphotangestic acid as efficient and reusable catalyst.
AB  - In this work, esterification of oleic acid by various alcohols is achieved with
      high yields under ultrasonic irradiation. This reaction performed with a novel
      heterogeneous catalyst that fabricated by heteropoly acid and Fe(III)-based MOF,
      namely MIL-53 (Fe). Syntheses of MIL-53 and encapsulation process carry out by
      ultrasound irradiation at ambient temperature and atmospheric pressure. The
      prepared composite was characterized by various techniques such as XRD, FT-IR,
      SEM, BET and ICP that demonstrate excellent catalytic activities, while being
      highly convenient to synthesize. The obtained results revealed that ultrasound
      irradiation could be used for the appropriate and rapid biodiesel production.

PMID- 28427625
TI  - Ultrasonic-assistant fabrication of cocoon-like Ag/AgFeO2 nanocatalyst with
      excellent plasmon enhanced visible-light photocatalytic activity.
AB  - The AgFeO2 delafossite was reported as a potential photocatalyst as well as its
      intense recombination rate of photogeneration charge carriers. In this work, we
      utilized plasmon modification method to enhance the photocatalytic activity of
      AgFeO2. Silkworm cocoon like Ag/AgFeO2 nanocatalyst was synthesized by an
      ultrasonic enhanced reduction method. XRD, HRTEM and XPS results demonstrated the
      well dispersed Ag0 on the surface of AgFeO2. Under visible light irradiation,
      20mg/L of ARG solution was completely degraded by 0.25g/L of Ag/AgFeO2
      photocatalyst with pseudo-first-order rate of 0.040min-1. The inducement of the
      prominently enhanced photocatalytic activity of Ag/AgFeO2 was deeply analyzed.
      Significant decreased intensity of photoluminescence (PL) spectra suggested the
      superior separation of photo-induced electrons and holes of Ag/AgFeO2 as compared
      to that of AgFeO2. The free h+ was confirmed as the dominant active species for
      the pollutant degradation. Ultimately, the photodegradation mechanism was
      proposed and discussed.

PMID- 28427627
TI  - Hydrothermal-precipitation preparation of CdS@(Er3+:Y3Al5O12/ZrO2) coated
      composite and sonocatalytic degradation of caffeine.
AB  - Here, we reported a novel method to dispose caffeine by means of ultrasound
      irradiation combinated with CdS@(Er3+:Y3Al5O12/ZrO2) coated composite as
      sonocatalyst. The CdS@(Er3+:Y3Al5O12/ZrO2) was synthesized via hydrothermal
      precipitation method and then characterized by X-ray diffractometer (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM),
      energy dispersive X-ray analysis (EDX) and UV-vis diffuse reflectance spectra
      (DRS). After that, the sonocatalytic degradation of caffeine in aqueous solution
      was conducted adopting CdS@(Er3+:Y3Al5O12/ZrO2) and CdS@ZrO2 coated composites as
      sonocatalysts. In addition, some influencing factors such as CdS and ZrO2 molar
      proportion, caffeine concentration, ultrasonic irradiation time, sonocatalyst
      dosage and addition of several inorganic oxidants on sonocatalytic degradation of
      caffeine were investigated by using UV-vis spectra and gas chromatograph. The
      experimental results showed that the presence of Er3+:Y3Al5O12 could effectively
      improve the sonocatalytic degradation activity of CdS@ZrO2. To a certain extent
      some inorganic oxidants can also enhance sonocatalytic degradation of caffeine in
      the presence of CdS@(Er3+:Y3Al5O12/ZrO2). The best sonocatalytic degradation
      ratio (94.00%) of caffeine could be obtained when the conditions of 5.00mg/L
      caffeine, 1.00g/L prepared CdS@(Er3+:Y3Al5O12/ZrO2), 10.00mmol/LK2S2O8, 180min
      ultrasonic irradiation (40kHz frequency and 50W output power), 100mL total volume
      and 25-28 degrees C temperature were adopted. It seems that the method of
      sonocatalytic degradation caused by CdS@(Er3+:Y3Al5O12/ZrO2)
      displayspotentialadvantages in disposing caffeine.

PMID- 28427626
TI  - Manothermosonication as a useful tool for lipid extraction from oleaginous
      microorganisms.
AB  - Manothermonication is a recognized and efficient method used for sterilization in
      food preservation. The synergistic effect of sonication combined with pressure
      and temperature allows enhancing the cavitation activity. Never employed for
      extraction, this study is about the transposition of this process as a tool of
      extraction. In this study, Rhodosporidium toruloides yeast was submitted to
      extraction by four modes of sonication, with a temperature ranged from 20 to 55
      degrees C and a pressure between 1 to 2bars. The lipids extraction yields were
      compared to the conventional maceration. Microbial oils obtained from both
      processes were analyzed and quantified by HPTLC (High Performance Thin-Layer
      Chromatography) and GC-FID (Gas Chromatography with flame ionization detector)
      after transesterification of lipids. Manothermosonication (30min, 2bars, 55
      degrees C) permits to enhance of approximately 20% the extraction yield of lipids
      to compared to conventional maceration. The fatty acid profiles of each
      pretreatment and extraction by US, MS, TS and MTS do not affect the fatty acid
      profiles of yeast (majority of oleic acid (C18:1n9), linoleic acid (C18:2n6) and
      palmitic acid (C16:0)). Manothermosonication technique shows a great potential
      for lipid extraction from oleaginous microorganisms.

PMID- 28427628
TI  - Ultrasonic energy enhanced the efficiency of advance extraction methodology for
      enrichment of trace level of copper in serum samples of patients having
      neurological disorders.
AB  - An innovative dual dispersive ionic liquid based on ultrasound assisted
      microextraction (UDIL-MUE), for the enrichment of trace levels of copper ion
      (Cu2+), in serum (blood) of patients suffering from different neurological
      disorders. The enriched metal ions were subjected to flame atomic absorption
      spectrometry (FAAS). In the UDIL-MUE method, the extraction solvent, ionic
      liquid, 1-butyl-3-methylimidazolium hexafluorophosphate [C4mim][PF6], was
      dispersed into the aqueous samples using an ultrasonic bath. The(PAN) 1-(2
      pyridylazo)-2-naphthol was used as ligand for the complexation of Cu ion in IL
      (as extracting solvent). The various variables such as sonication time, pH,
      concentration of complexing agent, time and rate of centrifugation, IL volume
      that affect the extraction process were optimized. The enhancement factor (EF)
      and detection limit (LOD) was found under favorable condition was 31 and 0.36MUgL
      1, respectively. Reliability of the proposed method was checked by relative
      standard deviation (%RSD), which was found to be <5%. The accuracy of developed
      procedure was assured by using certified reference material (CRM) of blood serum.
      The developed procedure was applied successfully to the analysis of concentration
      of Cu ion in blood serum of different neurological disorders subjects and
      referents of same age group. It was observed that the levels of Cu ion was two
      folds higher in serum samples of neurological disorders patients as related to
      normal referents of same age group.

PMID- 28427629
TI  - Development of a novel folate-modified nanobubbles with improved targeting
      ability to tumor cells.
AB  - Conjugation of folate (FOL) to nanobubbles could enhance the selective targeting
      to tumors expressing high levels of folate receptor (FR). To further improve the
      selective targeting ability of FOL-modified nanobubbles, a novel FOL-targeted
      nanobubble ((FOL)2-NB) with increasing FOL content (accomplished by linking two
      FOL molecules per DSPE-PEG2000 chain) was synthesized, through the methods of
      mechanical shaking and low-speed centrifugation based on lipid-stabilized
      perfluoropropane. The bubble size and distribution range were measured by dynamic
      light scattering (DLS). Enhanced imaging ability was evaluated using a custom
      made agarose mold with a clinical US imaging system at mechanical indices of up
      to 0.12 at a center frequency of 9.0MHz. Targeted ability was also carried out in
      human breast cancer MCF-7 cells, which over-express the FR, by fluorescence
      activated cell sorting (FACS) and fluorescence microscopy, respectively. (FOL)2
      NB with a particle size of 286.87+/-22.96nm were successfully prepared, and they
      exhibited superior contrast imaging effect. FACS and fluorescence microscopy
      studies showed greater cellular targeting ability in the group of (FOL)2-NB than
      in their control group of Non-targeted-NB (no FOL targeted nanobubbles) and FOL
      NB (one FOL molecule per DSPE-PEG2000 chain). These results suggest that a new
      type of stronger targeted nanobubble was successfully prepared by increasing the
      FOL content per DSPE-PEG2000 chain. This novel (FOL)2-NBs are potentially useful
      for ultrasound molecular imaging and treatment of FR-positive tumors and are
      worthy for further investigation.

PMID- 28427630
TI  - Porosity and dye adsorption enhancement by ultrasonic synthesized Cd(II) based
      metal-organic framework.
AB  - A Cd(II) based metal-organic framework, TMU-7, was synthesized by incorporation
      of V-shaped flexible dicarboxylate ligand and the N-donor pillar ligand using
      sonochemical method while morphology and size of particles were investigated and
      characterized by scanning electron microscopy and X-ray powder diffraction.
      Moreover, N2 adsorption was applied to examine the effect of synthesis method on
      porosity. Also TMU-7 was evaluated for its Congo red adsorption.

PMID- 28427631
TI  - Combined effect of ultrasound, heat, and pressure on Escherichia coli O157:H7,
      polyphenol oxidase activity, and anthocyanins in blueberry (Vaccinium corymbosum)
      juice.
AB  - The objective of this study was to evaluate the effect of different treatments
      heat treatment (HT), sonication (SC), thermosonication (TS), manosonication (MS),
      manothermal (MT), and manothermosonication (MTS) on Escherichia coli O157:H7,
      polyphenol oxidase (PPO), and anthocyanin content in blueberry juice. First,
      samples were treated at different temperatures (30, 40, 50, 60, 70, and 80
      degrees C) and power intensities (280, 420, 560, and 700W) for 10min.
      Subsequently, samples were treated using combinations of power intensity and mild
      temperature for 10min. For further study, samples were treated using HT (80
      degrees C), TS (40 degrees C, 560W), MT (350MPa, 40 degrees C), MS (560W,
      5min/350MPa), or MTS (560W, 5min, 40 degrees C/350MPa, 40 degrees C) for 5, 10,
      15, 20min for each treatment, and the results compared between treatments. HT
      significantly reduced PPO activation (2.05% residual activity after only 5min),
      and resulted in a 2.00-log reduction in E. coli O157:H7 and an 85.25% retention
      of anthocyanin. Escherichia coli O157:H7 was slightly inactivated by TS after
      5min (0.17-log reduction), while residual PPO activity was 23.36% and anthocyanin
      retention was 98.48%. However, Escherichia coli O157:H7 was rapidly inactivated
      by MTS (5.85-log reduction) after 5min, while anthocyanin retention was 97.49%
      and residual PPO activity dropped to 10.91%. The destruction of E. coli cells as
      a result of these treatments were confirmed using SEM and TEM. Therefore, a
      combination of sonication, high pressure, and mild heat allows the safety of
      blueberry juice to be maintained without compromising the retention of desirable
      antioxidant compounds.

PMID- 28427632
TI  - Ultrasonic treatment of CoFe2O4@B2O3-SiO2 as a new hybrid magnetic composite
      nanostructure and catalytic application in the synthesis of
      dihydroquinazolinones.
AB  - New hybrid magnetic composite nanostructure are prepared via ultrasonic treatment
      by glass-ceramic method, characterized by field-emission scanning electron
      microscopy (FE-SEM), X-ray diffraction (XRD), vibrating sample magnetometer
      (VSM), energy-dispersive X-ray (EDX), element distribution image (EDX mapping),
      thermal gravimetric analysis (TGA)/differential thermal analysis (DTA) and N2
      adsorption-desorption by Brunauer-Emmett-Teller (BET) analyses. Then, the
      catalytic activity of the prepared CoFe2O4@B2O3-SiO2 nanoparticles was tested in
      the synthesis of 2-substituted-3-(phenylamino)-dihydroquinazolin-4(1H)-ones in
      deep eutectic solvent (DES) based on choline chloride as an eco-friendly and
      recyclable media. This novel protocol offers several advantages such as high
      yields (70-93%), short reaction times (10-20min), environmentally-friendly
      reaction media, easily isolation of the products, simple preparation and
      recoverability of the nanocatalysts (at least 5 times), recyclability of the
      solvents from the reaction mixture without use of hazardous volatile organic
      solvent. The catalyst was readily recycled by the use of an external magnetic
      field and could be reused several times without significant loss of activity or
      mass. The saturation magnetization of CoFe2O4@B2O3-SiO2 nanoparticles was
      8.97emug-1. Their average size distribution was about 12.5nm. DES was a mixture
      of choline chloride and urea that was recovered from the filtrate by evaporating
      the water under vacuum.

PMID- 28427633
TI  - An efficient approach for the extraction of orientin and vitexin from Trollius
      chinensis flowers using ultrasonic circulating technique.
AB  - Ultrasonic circulating extraction (UCE) approach was developed for effective
      extraction of orientin and vitexin from the flowers of Trollius chinensis
      successfully. In this study, some parameters potentially influencing the yields
      of orientin and vitexin were systematically investigated and optimized by
      Plackett-Burman and Box-Behnken design, and the optimum operational conditions
      obtained were 60% ethanol volume fraction, 1000r/min stirring speed, 30 degrees C
      temperature, 28min ultrasonic irradiation time, 10mL/g liquid-solid ratio and
      738W ultrasonic irradiation power. Satisfactory yields of orientin (6.05+/
      0.19mg/g) and vitexin (0.96+/-0.03mg/g) were obtained in a relatively shorter
      extraction time under the derived optimum conditions, compared to other
      ultrasonic extraction methods and heat extraction methods. The mechanism of UCE
      procedure was discussed in detail, to illustrate the advantage of UCE in the
      extraction process. In addition, no degradation of orientin and vitexin and high
      reproducibility of the developed UCE method were observed under the optimum
      conditions. The proposed UCE technique with high-capacity and circulation
      function is a rapid and efficient sample extraction technique, and performs
      promising in large-scale sample preparation.

PMID- 28427634
TI  - Enhanced porosity and permeability of three-dimensional alginate scaffolds via
      acoustic microstreaming induced by low-intensity pulsed ultrasound.
AB  - The shear stress resulting from the microstreaming induced by low-intensity
      pulsed ultrasound (LIPUS) has been often used to improve the permeability of cell
      membrane or porous engineering scaffolds. In the present study, three-dimensional
      (3-D) scaffold culture systems were constituted to simulate the in vivo
      microenvironment, providing benefits for cell growth. In order to investigate the
      mechanism underlying the enhanced porosity and permeability of the 3-D alginate
      scaffolds by using LIPUS with varied acoustic intensities, two quantitative
      imaging techniques (i.e. scanning electron microscopy, and laser con-focal
      imaging) were used to evaluate the porosity and permeability of the 3-D alginate
      scaffolds. The results suggested that the porosity and permeability of the
      scaffolds were enhanced by the microbubble-induced microstreaming, and increased
      with the increasing LIPUS driving intensity. Furthermore, the cell proliferation
      assessments verified that HeLa cell grew better in the treated 3-D alginate
      scaffolds, since the LIPUS exposures can improve the scaffold porosity and
      permeability, leading to better cell growth space and nutrition supply.

PMID- 28427635
TI  - Sonochemical synthesis of two new zinc(II) 1,10-phenanthroline coordination
      supramolecular compounds: New precursors to produce nano-sized zinc(II) oxide.
AB  - Nanoparticles of two zinc(II) coordination supramolecule compounds (CSCs),
      [Zn(L)Cl2] (1) and [Zn(L)Br2] (2) L=1,10-phen=1,10-phenanthroline ligand, have
      been synthesized by use of a sonochemical process and characterized by scanning
      electron microscopy (SEM), X-ray powder diffraction (XRPD), Fourier transform
      infrared (FTIR) spectroscopy and elemental analyses. The single crystal X-ray
      data of compounds 1 and 2 imply that the Zn+2 ions are four coordinated.
      Topological analysis shows that the compound 1 and 2 are new topology for net:
      1,3M4-1. Nanoparticles of zinc(II) oxide have been prepared by calcination of two
      different zinc(II) CPs at 500 degrees C that were characterized by scanning
      electron microscopy (SEM), X-ray powder diffraction (XRD) and IR spectroscopy.

PMID- 28427636
TI  - Ultrasound-assisted synthesis of nano-structured Zinc(II)-based metal-organic
      frameworks as precursors for the synthesis of ZnO nano-structures.
AB  - A 3D, porous Zn(II)-based metal-organic framework {[Zn2(oba)2(4-bpmn)].(DMF)1.5}n
      (TMU-21), (4-bpmn=N,N'-Bis-pyridin-4-ylmethylene-naphtalene-1,5-diamine,
      H2oba=4,4'-oxybis(benzoic acid)) with nano-rods morphology under ultrasonic
      irradiation at ambient temperature and atmospheric pressure was prepared and
      characterized by scanning electron microscopy. Sonication time and concentration
      of initial reagents effects on the size and morphology of nano-structured MOFs
      were studied. Also {[Zn2(oba)2(4-bpmn)] (TMU-21) and {[Zn2(oba)2(4-bpmb)] (TMU
      6), 4-bpmb=N,N'-(1,4-phenylene)bis(1-(pyridin-4-yl)methanimine) were easily
      prepared by mechanochemical synthesis. Nanostructures of Zinc(II) oxide were
      obtained by calcination of these compounds and their de-solvated analogue as
      activated MOFs, at 550 degrees C under air atmosphere. As a result of that,
      different Nanostructures of Zinc(II) oxide were obtained. The ZnO nanoparticles
      were characterized by powder X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and FT-IR spectroscopy.

PMID- 28427637
TI  - Ultrasound-assisted degradation of organic dyes over magnetic CoFe2O4@ZnS core
      shell nanocomposite.
AB  - Magnetic CoFe2O4@ZnS core-shell nanocomposite was successfully synthesized via
      one-step hydrothermal decomposition of zinc(II) diethanoldithiocarbamate complex
      over CoFe2O4 nanoparticles at low temperature of 200 degrees C. The obtained
      nanocomposite was characterized by X-ray diffraction, Fourier-transform infrared
      spectroscopy, UV-Vis spectroscopy, field emission scanning electron microscopy,
      energy-dispersive X-ray spectroscopy, magnetic measurements, and Brunauere
      Emmette-Teller. The results confirmed the formation of CoFe2O4@ZnS nanocomposite
      with the average crystallite size of 18nm. The band gap of 3.4eV was obtained
      using UV-vis absorption of CoFe2O4@ZnS nanocomposite, which made it a suitable
      candidate for sono-/photo catalytic processes. This nanocomposite was applied as
      a novel sonocatalyst for the degradation of organic pollutants under ultrasound
      irradiation. The results showed complete degradation of methylene blue (MB)
      (25mg/L) within 70min in the presence of CoFe2O4@ZnS nanocomposite and H2O2
      (4mM). The trapping experiments indicated that OH radicals are the main active
      species in dye degradation. In addition, sonocatalytic activity of the
      CoFe2O4@ZnS nanocomposite was higher than those of pure ZnS and CoFe2O4, showing
      that the combining ZnS with magnetic CoFe2O4 could be an excellent choice to
      improve its sonocatalytic activity. The nanocomposite could be magnetically
      separated and reused without any observable change in its structure and
      performance even after five consecutive runs.

PMID- 28427639
TI  - Synergistic degradation of antibiotic norfloxacin in a novel heterogeneous
      sonochemical Fe0/tetraphosphate Fenton-like system.
AB  - In this study, synergistic degradation of antibiotic norfloxacin (NOR) was
      obtained in a novel sonochemical ultrasound/zero-valent iron/tetraphosphate
      system (US/ZVI/TPP). Compared to three common organic ligands (EDTA, EDDS, and
      DTPA), TPP could perform more excellently in activation of O2 to produce reactive
      oxidative species (ROS) and lead to efficient Fenton-like oxidative degradation
      of NOR in the sonochemical in situ chemical oxidation (ISCO) system. An optimized
      initial condition was obtained as 10mg/L NOR, 0.3mM TPP, 1g/L ZVI and initial pH
      7, and the US/ZVI/TPP system would effectively degrade NOR with relative low
      dosage of ZVI and ligand as well as broad pH work range 3-9. It was found that
      three ROS (OH, O2- and H2O2) instead of OH only would participate in the NOR
      degradation, while the in situ generation of H2O2 during the series of Fe-TPP
      reactions should be more critical. Fourteen organic intermediates and four
      inorganic products were detected during the NOR decomposition, suggesting that
      two main degradation pathways would occur under OH oxidation via cleavage of the
      piperazine ring and defluorination of the benzene ring, respectively. Finally, an
      integrated reaction mechanism in the US/ZVI/TPP system was proposed including
      solid-liquid interfacial iron corrosion as well as bulk homogenous oxygen
      activation and Fenton reactions, wherein US would play mechanically and
      chemically promotional roles. Besides, triple-repeated treatments suggested the
      relative long-term re-usage of ZVI particles and low effluent dissolved iron
      (<0.6mg/L).

PMID- 28427638
TI  - A new approach of probe sonication assisted ionic liquid conversion of glucose,
      cellulose and biomass into 5-hydroxymethylfurfural.
AB  - 5-Hydroxymethylfurfural (HMF) has been identified as a promising biomass-derived
      platform chemical. In this study, one pot production of HMF was studied in ionic
      liquid (IL) under probe sonication technique. Compared with the conventional
      heating technique, the use of probe ultrasonic irradiation reduced the reaction
      time from hours to minutes. Glucose, cellulose and local bamboo, treated with
      ultrasonic, produced HMF in the yields of 43%, 31% and 13% respectively, within
      less than 10min. The influence of various parameters such as acoustic power,
      reaction time, catalysts and glucose loading were studied. About 40% HMF yield at
      glucose conversion above 90% could be obtained with 2% of catalyst in 3min.
      Negligible amount of soluble by-product was detected, and humin formation could
      be controlled by adjusting the different process parameters. Upon extraction of
      HMF, the mixture of ionic liquid and catalyst could be reused and exhibited no
      significant reduction of HMF yield over five successive runs. The purity of
      regenerated [C4C1im]Cl and HMF was confirmed by NMR spectroscopy, indicating
      neither changes in the chemical structure nor presence of any major contaminants
      during the conversion under ultrasonic treatment. 13C NMR suggests that
      [C4C1im]Cl/CrCl3 catalyses mutarotation of alpha-glucopyranose to beta
      glucopyranose leading to isomerization and finally conversion to HMF. The
      experimental results demonstrate that the use of probe sonication technique for
      conversion to HMF provides a positive process benefit.

PMID- 28427640
TI  - Comparative evaluation of maceration and ultrasonic-assisted extraction of
      phenolic compounds from fresh olives.
AB  - Ultrasonic-assisted extraction (UAE) and maceration extraction (ME) were
      optimized using response surface methodology (RSM) for total phenolic compounds
      (TPC) from fresh olives. The main phenolic compounds and antioxidant activity of
      TPC were also investigated. The optimized result for UAE was 22mL/g of liquid
      solid ratio, 47 degrees C of extraction temperature and 30min of extraction time,
      7.01mg/g of yielding, and for ME was 24mL/g of liquid-solid ratio, 50 degrees C
      of extraction temperature and 4.7h of extraction time, 5.18mg/g of yielding. The
      HPLC analysis revealed that the extracts by UAE and ME possessed 14 main phenolic
      compounds, and UAE exhibited more amounts of all phenols than ME. The most
      abundant phenolic compounds in olive extracts were hydroxytyrosol, oleuropein and
      rutin. Both extracts showed excellent antioxidant activity in a dose-dependent
      manner. Taken together, UAE could effectively increase the yield of phenolic
      compounds from olives. In addition these phenolic compounds could be used as a
      potential source of natural antioxidants.

PMID- 28427641
TI  - Facile sonochemical synthesis of tellurium and tellurium dioxide nanoparticles:
      Reducing Te(IV) to Te via ultrasonic irradiation in methanol.
AB  - In this study, tellurium (Te) nanostructures were synthesized via a facile
      sonochemical method by reducing TeCl4 to Te under ultrasonic irradiation in
      methanol. Moreover, by carrying out the reaction in an alkaline environment TeO2
      nanoparticles were produced. According to our knowledge, it is the first time
      that without secondary reducing agent Te4+ are reduced to Te. Also, the effects
      of ultrasonic power, irradiation time, solvent, and surfactant on the morphology
      and particle size of Te nanostructures were investigated. The obtained products
      were characterized by XRD, SEM, EDS, FT-IR and DRS.

PMID- 28427642
TI  - Improvement of sonochemical degradation of Brilliant blue R in water using
      periodate ions: Implication of iodine radicals in the oxidation process.
AB  - In this paper, the effect of periodate (IO4-) on the ultrasonic degradation at
      300kHz of Brilliant Blue R (BBR), an organic dye pollutant, was investigated. The
      experiments were realized in the absence and presence of periodate for various
      operating conditions including initial solution pH (2-8) and delivered ultrasonic
      power (20-80W). It was found that periodate greatly enhanced the sonochemical
      degradation of BBR. The degradation rate increased significantly with increasing
      IO4- concentration up to 10mM and decreased afterward. With 10mM of periodate,
      the degradation rate was 2.4-fold higher than that with ultrasound alone. The
      chemical probes experiments showed that periodate activation into free radicals
      (IO3, IO4 and OH) takes place by sonolysis and iodine radicals contribute
      significantly in the oxidation process. It was found that the periodate-enhanced
      effect was strongly experimental parameters dependent. The advantageous effect of
      periodate increased significantly with decreasing power and the best enhancing
      effect was obtained for the lowest power. Correspondingly, the periodate-enhanced
      effect increased with pH increase in the range 2-8 and it was more remarkable at
      near alkaline condition (pH 8). A reaction scheme for periodate sonolysis was
      proposed, for the first time, discussed and then used for interpreting the
      obtained results.

PMID- 28427643
TI  - Improving the enzymolysis efficiency of potato protein by simultaneous dual
      frequency energy-gathered ultrasound pretreatment: Thermodynamics and kinetics.
AB  - The thermodynamics and kinetics of traditional and simultaneous dual frequency
      energy-gathered ultrasound (SDFU) assisted enzymolysis of potato protein were
      investigated to get the knowledge of the mechanisms on the SDFU's promoting
      efficiency during enzymolysis. The concentration of potato protein hydrolysate
      and parameters of thermodynamic and kinetic during traditional and SDFU assisted
      enzymolysis were determined. The results showed that potato protein hydrolysate
      concentration of SDFU assisted enzymolysis was higher than traditional
      enzymolysis at the hydrolysis time of 60min (p<0.05) whereas not significantly
      different at 120min (p>0.05). In some cases, SDFU assisted enzymolysis took less
      hydrolysis time than traditional enzymolysis when the similar conversion rates of
      potato protein were obtained. The thermodynamic papameters including the energy
      of activation (Ea), enthalpy of activation (?H), entropy of activation (?S) were
      reduced by ultrasound pretreatment while Gibbs free energy of activation (?G)
      increased little (1.6%). Also, kinetic papameters including Michaelis constant
      (KM) and catalytic rate constant (kcat) decreased by ultrasound pretreatment. On
      the contrary, reaction rate constants (k) of SDFU assisted enzymolysis were
      higher than that of traditional enzymolysis (p<0.05). It was indicated that the
      efficiency of SDFU assisted enzymolysis was higher than traditional enzymolysis
      in a limited time. The higher efficiency of SDFU assisted enzymolysis was related
      with the decrease of Ea and KM by lowering the energy barrier between ground and
      active state and increasing affinity between substrate and enzyme.

PMID- 28427644
TI  - Optimization of ultrasonication period for better dispersion and stability of
      TiO2-water nanofluid.
AB  - Nanofluids are promising in many fields, including engineering and medicine.
      Stability deterioration may be a critical constraint for potential applications
      of nanofluids. Proper ultrasonication can improve the stability, and possibility
      of the safe use of nanofluids in different applications. In this study, stability
      properties of TiO2-H2O nanofluid for varying ultrasonication durations were
      tested. The nanofluids were prepared through two-step method; and electron
      microscopies, with particle size distribution and zeta potential analyses were
      conducted for the evaluation of their stability. Results showed the positive
      impact of ultrasonication on nanofluid dispersion properties up to some extent.
      Ultrasonication longer than 150min resulted in re-agglomeration of nanoparticles.
      Therefore, ultrasonication for 150min was the optimum period yielding highest
      stability. A regression analysis was also done in order to relate the average
      cluster size and ultrasonication time to zeta potential. It can be concluded that
      performing analytical imaging and colloidal property evaluation during and after
      the sample preparation leads to reliable insights.

PMID- 28427646
TI  - Investigate the ultrasound energy assisted adsorption mechanism of nickel(II)
      ions onto modified magnetic cobalt ferrite nanoparticles: Multivariate
      optimization.
AB  - In present study, magnetic cobalt ferrite nanoparticles modified with (E)-N-(2
      nitrobenzylidene)-2-(2-(2-nitrophenyl)imidazolidine-1-yl) ethaneamine (CoFe2O4
      NPs-NBNPIEA) was synthesized and applied as novel adsorbent for ultrasound energy
      assisted adsorption of nickel(II) ions (Ni2+) from aqueous solution. The prepared
      adsorbent characterized by Fourier transforms infrared spectroscopy (FT-IR),
      transmission electron microscope (TEM), vibrating sample magnetometer (VSM) and X
      ray diffraction (XRD). The dependency of adsorption percentage to variables such
      as pH, initial Ni2+ ions concentration, adsorbent mass and ultrasound time were
      studied with response surface methodology (RSM) by considering the desirable
      functions. The quadratic model between the dependent and independent variables
      was built. The proposed method showed good agreement between the experimental
      data and predictive value, and it has been successfully employed to adsorption of
      Ni2+ ions from aqueous solution. Subsequently, the experimental equilibrium data
      at different concentration of Ni2+ ions and 10mg amount of adsorbent mass was
      fitted to conventional isotherm models like Langmuir, Freundlich, Tempkin,
      Dubinin-Radushkevich and it was revealed that the Langmuir is best model for
      explanation of behavior of experimental data. In addition, conventional kinetic
      models such as pseudo-first and second-order, Elovich and intraparticle diffusion
      were applied and it was seen that pseudo-second-order equation is suitable to fit
      the experimental data.

PMID- 28427645
TI  - Ultrasound-assisted extraction of Achyrocline satureioides prevents contrast
      induced nephropathy in mice.
AB  - Achyrocline satureioides or Macela, has been largely used in traditional folk
      medicine in Brazil as an anti-inflammatory agent and to treat various digestive
      disorders. The aim of the present study was to evaluate the preventive action of
      the extracts of A. satureioides obtained by maceration and ultrasound-assisted
      extraction, quercetin and N-acetylcysteine against contrast-induced nephropathy
      in mice. The antioxidant activity, cytotoxicity and inhibition of nitric oxide
      (NO) production in macrophages were evaluated. Also, chemical analyses of
      phenolic compounds, total flavonoids, and quercetin by LC-MS/MS present in
      various extracts of A. satureioides were performed. Thirty six mice were divided
      into six groups: control group (C), Contrast-Induced Nephropathy group (CIN),
      Group N-acetylcysteine 200mg/kg (NAC); Group quercetin 10mg/kg (Q), Group Macela
      10mg/kg (M10), and Group Macela 50mg/kg (M50). The serum levels of urea and
      creatinine, advanced oxidation protein products (AOPP) and renal ultrastructure
      were evaluated by electron microscopy scanning. Ultrasound-assisted extraction
      improved the quality of extract (with 100% ethanol), since did not show toxicity
      to fibroblasts, and showed potent antioxidant activity and a high content of
      phenolic compounds, flavonoids, and quercetin, in addition to being able to
      reduce the production of NO in dose-dependent effect in macrophages. Results
      showed that animals treated with Macela extracts maintained normal levels of
      urea, creatinine, and AOPP, while preserving ultrastructure of the renal cells.
      The obtained results were more promising than NAC and Q groups in protecting
      against renal failure caused by CIN, showing that the plant can be a promising
      drug for preventing this disease.

PMID- 28427647
TI  - Ascorbic acid stability in fruit juices during thermosonication.
AB  - Thermosonication is an emerging technology useful for inactivating microorganisms
      and enzymes in fruit juices. However, the effect of the ultrasound processing on
      the ascorbic acid content is not clear and the results reported in the literature
      are contradictory. In this work, the impact of sonication and thermosonication on
      the ascorbic acid content was first evaluated in model systems. Degassed model
      solutions at four different pH values (3-6) were processed with or without
      sonication for 60min at two different conditions of temperature (25 and 55
      degrees C). In all cases, the ascorbic acid was stable under the treatment. After
      that, two commercial deaerated fruit juices were processed with and without US at
      55 degrees C. The ascorbic acid was also retained in these juices after the
      ultrasound processing under the most severe conditions studied. In conclusion,
      previous degassing/deaerating of fruit juices is recommended to prevent ascorbic
      acid degradation when thermosonication is applied.

PMID- 28427648
TI  - Sonochemical synthesis, characterization, and effects of temperature, power
      ultrasound and reaction time on the morphological properties of two new
      nanostructured mercury(II) coordination supramolecule compounds.
AB  - Two new mercury(II) coordination supramolecular compounds (CSCs) (1D and 0D),
      [Hg(L)(I)2]n (1) and [Hg2(L')2(SCN)2].2H2O (2) (L=2-amino-4-methylpyridine and
      L'=2,6-pyridinedicarboxlic acid), have been synthesized under different
      experimental conditions. Micrometric crystals (bulk) or nano-sized materials have
      been obtained depending on using the branch tube method or sonochemical
      irradiation. All materials have been characterized by field emission scanning
      electron microscope (FESEM), scanning electron microscopy (SEM), powder X-ray
      diffraction (PXRD) and FT-IR spectroscopy. Single crystal X-ray analyses on
      compounds 1 and 2 show that Hg2+ ions are 4-coordinated and 5-coordinated,
      respectively. Topological analysis shows that the compound 1 and 2 have 2C1, sql
      net. The thermal stability of compounds 1 and 2 in bulk and nano-size has been
      studied by thermal gravimetric (TG), differential thermal analyses (DTA) for 1
      and differential scanning calorimetry (DSC) for 2, respectively. Also, by
      changing counter ions were obtained various structures 1 and 2 (1D and 0D,
      respectively). The role of different parameters like power of ultrasound
      irradiation, reaction time and temperature on the growth and morphology of the
      nano-structures are studied. Results suggest that increasing power ultrasound
      irradiation and temperature together with reducing reaction time and
      concentration of initial reagents leads to a decrease in particle size.

PMID- 28427649
TI  - Hydrodynamic cavitation in combination with the ozone, hydrogen peroxide and the
      UV-based advanced oxidation processes for the removal of natural organic matter
      from drinking water.
AB  - Natural organic matter in drinking water is causing concern especially due to the
      formation of disinfection by-products (DBPs) by chlorine, as these are proven to
      have adverse health effects on consumers. In this research, humic acid was used
      as a source of dissolved organic carbon (DOC) in drinking water (up to 3mgL-1).
      The efficiency of DOC removal was studied by applying O3, H2O2/O3, H2O2/UV and
      O3/UV advanced oxidation processes (AOPs) alone and combined with hybrid
      hydrodynamic cavitation (HC), generated by an orifice plate, as this technology
      recently shows promising potential for the treatment of water, containing
      recalcitrant organic substances. It was observed that the combined treatment by
      HC could significantly affect the performance of the applied AOPs, with as little
      as 3-9 passes through the cavitation generators. For O3 and H2O2 dosages up to 2
      and 4mgL-1, respectively, and UV dosage up to 300mJcm-2, HC enhanced DOC removal
      by 5-15% in all combinations, except for O3/UV AOPs. Overall, the potential
      benefits of HC for DOC removal were emphasized for low ratio between applied
      oxidants to DOC and high UV absorbance of the sample. Investigated DBPs formation
      potentials require special attention for H2O2/UV AOPs and combinations with HC.

PMID- 28427650
TI  - Effect of ultrasound on the interaction between (-)-epicatechin gallate and
      bovine serum albumin in a model wine.
AB  - Ultrasound is considered as a potential novel technique for improving the quality
      of some wines. In this paper, a model wine firstly was constructed with the
      standards of (-)-epicatechin gallate (ECG) and bovine serum albumin (BSA) as
      target compounds. Then, the experiments were conducted to investigate the effect
      of ultrasonic irradiation on the binding properties between ECG and BSA including
      quenching mechanism, binding parameters, binding forces, energy transfer distance
      and conformational changes determined by spectral analysis. The results indicate
      that ultrasound definitely has some regular effects on the binding interaction of
      BSA and ECG, and can induced the conformation variation of BSA in the simulated
      wine, which may suggest that the ultrasound might be employed to modify the wine
      organoleptic property by regulating the interaction between phenolic compounds
      and proteins from the autolysis of yeasts, since they are similar to the
      standards of ECG and BSA, respectively.

PMID- 28427651
TI  - Ultrasonic synthesis of two nanostructured cadmium(II) coordination
      supramolecular polymers: Solvent influence, luminescence and photocatalytic
      properties.
AB  - Two nanoparticles of cadmium(II) coordination polymers (CPs) formulated as
      [Cd(L)(DCTP)]n (1) and [Cd(L)2(DCTP).2H2O]n (2) (L=1,2-bis(2-methylbenzimidazol-1
      ylmethyl)benzene, H2DCTP=2,5-dichloroterephthalic acid) were prepared by the
      sonochemical approach in different solvents and characterized by elemental
      analysis, IR spectra, scanning electron microscopy (SEM), and powder X-ray
      diffraction. Structural determination reveals that CP 1 displays a 2D four
      connected sql net layer, Whilst CP 2 exhibits a 1D "V"-like chain structure.
      Luminescence properties, thermal behavior, and photocatalytic activities of the
      nanoparticles of CPs 1 and 2 on the degradation of methylene blue were
      investigated. The photocatalytic mechanism is carried out by introducing t-butyl
      alcohol (TBA) as a widely used OH scavenger. Furthermore, the influence of
      solvents, reaction time, and ultrasound irradiation temperature on the morphology
      and size of the nanostructure CPs 1 and 2 were investigated. The results
      indicated that an increase of time and ultrasound irradiation temperature
      decreased the nanostructured size.

PMID- 28427652
TI  - Ultrasonic modification of starch - Impact on granules porosity.
AB  - Rice, corn, wheat, and potato starch granules suspended in water or ethanol were
      treated with ultrasounds at frequency of 20kHz and power 170W for 30min. Porosity
      of starch was investigated in terms of specific surface area (SBET), average pore
      size and pore size distribution using low-temperature nitrogen adsorption method.
      The significant increase of SBET was noted for all the studied starches sonicated
      in water and for potato starch modified in ethanol. Ultrasonic treatment
      influenced the average diameter of mesopores (2nm<width<50nm) differently. The
      significant increase of this parameter was noted for wheat and rice starches
      suspended in ethanol and for potato starch granules suspended in water, but in
      the case of corn starch, the obtained value was slightly lower after sonication
      in water. Modification of starch with ultrasounds resulted in the formation of
      new pores in the studied range of diameter.

PMID- 28427653
TI  - Thermolysis synthesis of pure phase NiO from novel sonochemical synthesized
      Ni(II) nano metal-organic supramolecular architecture.
AB  - Nano-structures of a new supramolecular coordination compound of divalent nickel
      with the pyrazol (pzH) containing the terminal azide anions, [Ni(pzH)2(N3)2] (1),
      with discrete molecular architecture (DMA) in solid state was synthesized via
      sonochemical method. The new nanostructure was characterized by scanning electron
      microscopy, X-ray powder diffraction, IR, and elemental analysis. Compound 1 was
      structurally characterized by single crystal X-ray diffraction and the single
      crystal X-ray data shows that the coordination number of Ni (II) ions is six,
      (NiN6), with four N-donor atoms from neutral "pzH" ligands and two N-donors from
      two terminal azide anions. The supramolecular features in these complexes are
      guided and controlled by weak directional intermolecular interactions. The
      structure of the title complex was optimized by density functional theory
      calculations. Calculated structural parameters and IR spectra for the title
      complex are consistent with the crystal structure. The NiO nanoparticles were
      obtained by thermolysis of 1 at 180 degrees C with oleic acid as a surfactant.

PMID- 28427654
TI  - Effect of high-intensity ultrasound on the technofunctional properties and
      structure of jackfruit (Artocarpus heterophyllus) seed protein isolate.
AB  - The influence of high-intensity ultrasound (HIU) on the technofunctional
      properties and structure of jackfruit seed protein isolate (JSPI) was
      investigated. Protein solutions (10%, w/v) were sonicated for 15min at 20kHz to
      the following levels of power output: 200, 400, and 600W (pulse duration: on
      time, 5s; off-time 1s). Compared with untreated JSPI, HIU at 200W and 400W
      improved the oil holding capacity (OHC) and emulsifying capacity (EC), but the
      emulsifying activity (EA) and emulsion stability (ES) increased at 400W and 600W.
      The foaming capacity (FC) increased after all HIU treatments, as opposed to the
      water holding capacity (WHC), least gelation concentration (LGC), and foaming
      stability (FS), which all decreased except at pH 4 for FS. Tricine sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (Tricine-SDS-PAGE) showed changes in
      the molecular weight of protein fractions after HIU treatment. Scanning electron
      microscopy (SEM) demonstrated that HIU disrupted the microstructure of JSPI,
      exhibiting larger aggregates. Surface hydrophobicity and protein solubility of
      the JSPI dispersions were enhanced after ultrasonication, which increased the
      destruction of internal hydrophobic interactions of protein molecules and
      accelerated the molecular motion of proteins to cause protein aggregation. These
      changes in the technofunctional and structural properties of JSPI could meet the
      complex needs of manufactured food products.

PMID- 28427655
TI  - Effect of ultrasound and enzymatic pre-treatment on yield and properties of
      banana juice.
AB  - Effect of ultrasound and enzymatic pre-treatments with cellulase and pectinase on
      yield and properties of banana juice were investigated. A two-level full
      factorial design was employed. The factors selected were ultrasonication time (0
      and 30min), cellulase concentration (0 and 0.2%) and pectinase concentration (0
      and 0.2%). The responses studied were yield, viscosity, clarity, total soluble
      solids (TSS) and pH. It was observed that pectinase was more effective in
      increasing the yield of juice compared to cellulase. Ultrasonic pre-treatment
      alone did not significantly increase the yield of juice. When ultrasound was
      combined with pre-treatment with both the enzymes maximum yield of 89.40% was
      obtained compared to 47.30% in the control. The viscosity of the juice decreased
      with addition of enzymes and with application of ultrasound. The clarity of the
      juice was not affected by cellulase treatment, but improved with pectinase
      treatment. Ultrasonication alone was found to be more effective than pectinase or
      cellulase treatment in improving the clarity of the juice. The TSS increased with
      enzymatic treatment, ultrasonication and their combination. pH was not affected
      by treatment type, but was found to be lower for the treated juices. Significant
      correlations were observed between the various responses.

PMID- 28427656
TI  - Ultrasonically assisted removal of Congo Red, Phloxine B and Fast green FCF in
      ternary mixture using novel nanocomposite following their simultaneous analysis
      by derivative spectrophotometry.
AB  - In this study dependency of simultaneous adsorption of Congo Red (CR), Phloxine B
      (BP) and Fast green FCF (FG) onto CuS/ZnS nanocomposites loaded on activated
      carbon (CuS/ZnS-NCs-AC) to pH, adsorbent mass, sonication time and initial dyes
      concentration were modeled and optimized, while CuS/ZnS-NCs-AC was identified by
      XRD, FESEM and EDS analysis. CR, PB and FG concentration determination were
      undertaken by first and second order derivative spectrophotometry in ternary
      mixture. According to central composite design (CCD) based on desirability
      function (DF), the best experimental conditions was set as pH 6.0, 0.02g CuS/ZnS
      NCs-AC, 5min sonication time, 15mgL-1 for PB and 10mgL-1 for other dyes.
      Conduction of experiments to above conditions lead to highest dyes removal
      efficiency of 99.72, 98.8 and 98.17 for CR, PB and FG, respectively. The
      adsorption data efficiently fitted by Langmuir isotherm model, while the order of
      maximum adsorption capacity (Qmax) for PB (128.21mgg-1)>CR (88.57mgg-1)>FG
      (73.40mgg-1) is related to their different structure and charges. Kinetics of
      process was efficiently explained according to pseudo-second-order kinetic in
      cooperation of Weber and Morris based on intraparticle diffusion.

PMID- 28427657
TI  - Tube reactors as a novel ultrasonication system for trouble-free treatment of
      sludges.
AB  - The performance of a novel low-maintenance tube reactor for ultrasonic treatment
      of sludge has been evaluated. The effects of sonication on the release of soluble
      chemical oxygen demand (sCOD) and anaerobic digestibility of raw and digested
      sewage sludge as well as agricultural sludge were studied. Results suggest that
      solubilization and digestibility is dependent on both type of sludge and the
      energy input. Digested and raw sludge showed high degree of solubilization,
      however, methane production was only increased for digested sludge. Agricultural
      sludge was not significantly affected by ultrasonic treatment neither concerning
      sCOD release nor methane production. The configuration of the ultrasonic system
      (serial vs. parallel operation) did not show a significant difference in both
      sCOD release and methane production. However, parallel operation tends to perform
      better for digested sludge, while serial operation tends to perform better for
      raw sludge. The strongest effect was observed for the treatment of digested
      sludge by increasing the methane production by more than 60%, although with a
      very intensive energy input of more than 5,000kJ per kg total solids. Hence, tube
      reactors seem to be an attractive alternative to sonotrode-based systems
      achieving similar performance at low maintenance with great potential especially
      for digested sludge.

PMID- 28427658
TI  - Influence of ultrasound-assisted extraction on the pyrolysis characteristics and
      kinetic parameters of eucalyptus.
AB  - In this study, the influence of ultrasound-assisted extraction on eucalyptus
      samples with special focus on pyrolysis characteristics and kinetic parameters
      was explored. Ultrasound and Soxhlet extraction were used to pretreat samples
      respectively, then samples were assayed by component analysis, TG-FTIR, and
      kinetic analysis. Ultrasound-assisted extraction did change the physiochemical
      characteristics of eucalyptus samples, particularly in regards to the quantity of
      extractives obtained. In TG and DTG curves, ultrasound-extracted samples
      reflected lower residual weight ratio (17.77%) and higher maximum weight loss
      rate (-22.92%/min), and were accompanied by a slight shift in the weight loss
      rate peak to lower temperature (366 degrees C). The volatiles produced during
      pyrolysis and the discrepancies of product distribution between experimental and
      controlled groups were explored based on TG-FTIR spectra. According to kinetic
      analysis results, ultrasound-treated samples showed higher activation energy at
      the primary portion of thermal degradation with an average of 206.09kJ/mol.

PMID- 28427659
TI  - Synergistic extraction of gold from the refractory gold ore via ultrasound and
      chlorination-oxidation.
AB  - A synergistic extraction method for gold from the refractory gold ores via
      ultrasound and chlorination-oxidation was developed. The effects of solid-liquid
      ratio, extraction time, ultrasound power, NaClO concentration and NaOH
      concentration on the extraction rate of gold from the refractory gold ore were
      investigated. The optimum conditions were as follows: NaClO concentration of
      1.5mol/L, NaOH concentration of 1.5mol/L, solid-liquid ratio of 5, ultrasound
      power of 200W and ultrasound time of 2h. Under the optimal conditions, 68.55% of
      gold was extracted. However, only 45.8% of gold was extracted after 6h without
      the ultrasound-assisted extraction. XRD and SEM were used to analyze the
      influence of ultrasound on the mineral properties and strengthening mechanism.
      The results showed that the interface layer was peeled, new surface was exposed,
      reaction resistance was reduced, the liquid-solid reaction was promoted and
      reaction speed was greatly improved under ultrasound. According to the results of
      range and variance analysis, the optimum leaching experiment with orthogonal
      design was almost identical with the optimum experiment of single factor. Among
      them, the ultrasound power was the most significant factors affecting leaching
      rate of gold. Compared with other extraction method, the synergistic extraction
      process decomposed completely sulfide and improved significantly the extraction
      rate of gold.

PMID- 28427660
TI  - Ultrasound processed nanoemulsion: A comparative approach between resveratrol and
      resveratrol cyclodextrin inclusion complex to study its binding interactions,
      antioxidant activity and UV light stability.
AB  - Resveratrol is a naturally occurring therapeutic molecule used for treatment of
      diseases caused by oxidative stress. This investigation elucidates the advantages
      of fabrication of size controlled resveratrol inclusion complex. This has been
      done by encapsulating resveratrol-cyclodextrin inclusion complex in a
      phospholipid stabilized nanoemulsion formulated by ultrasonication emulsification
      method. The prepared nanoemulsion has been compared with resveratrol encapsulated
      nanoemulsion system. The morphology of the resveratrol nanoemulsion and inclusion
      complex nanoemulsion have been observed using transmission electron microscopy
      with average size 20.41+/-3.41 and 24.48+/-5.70nm respectively. The nanoemulsion
      showed good loading and release efficiency. The radical diminishing potential of
      resveratrol and its inclusion complex has been compared in nanoemulsion. The
      effect of UV irradiation (365nm) on resveratrol in different solvent systems
      (ethanol, water and nanoemulsion) indicated that nanoemulsion prevents
      degradation of resveratrol. Efforts have also been made to explore the
      interactions between bovine serum albumin and resveratrol in nanoemulsion.

PMID- 28427661
TI  - Sono-dispersion of TiO2 nanoparticles over clinoptilolite used in photocatalytic
      hydrogen production: Effect of ultrasound irradiation during conventional
      synthesis methods.
AB  - Hydrogen evolution via water splitting was investigated over the sonochemically
      synthesized TiO2-clinoptilolite photocomposites. To this aim, a series of
      photocatalysts containing 10wt% titania were prepared by impregnation and solid
      state dispersion (SSD) methods in the presence and absence of ultrasound
      irradiation. The samples were characterized by XRD, FESEM, EDX, BET, FTIR, PL and
      UV-vis techniques and tested for the water splitting. The characterization
      results indicated that ultrasound irradiation endowed the photocatalysts with
      uniform morphology, higher surface area and more homogenous dispersion. In
      addition, the analyses also exhibited less population of particle aggregates, a
      strong titania-support interaction and lower electron-hole pairs recombination
      rate. These features were more prominent when ultrasound was employed during SSD
      method. The TiO2/Clinoptilolite photocatalyst prepared by the ultrasound assisted
      SSD method (TiO2/CLT(US)), had more uniform active sites dispersion, high
      separation efficiency of electron-hole pairs and as a consequence, high surface
      density of active sites. The highest photocatalytic activity, 569.88 [Formula:
      see text] , was obtained for the TiO2/CLT(US) sample which was about 8 times more
      than that of P-25 as a reference sample. Furthermore, the TiO2/CLT(US)
      photocomposite as optimal photocatalyst showed sufficient reusability, making it
      a good choice for photocatalytic water splitting applications.

PMID- 28427662
TI  - Ultrasonic assisted synthesis of a tetrazine functionalized MOF and its
      application in colorimetric detection of phenylhydrazine.
AB  - TMU-34(-2H), [Zn(OBA)(DPT)0.5].DMF, has been sonochemically synthesized by
      applying H2OBA, (4,4'-oxybis(benzoic acid)), as the dicarboxylate linker, and
      DPT, (3,6-di(pyridin-4-yl)-1,2,4,5-tetrazine), as pillar spacer. Sonication time,
      concentration of initial reagents, sonication power and molar ratio of pyridine
      as modulator has been optimized to synthesize nano powder of TMU-34(-2H)
      including uniform plate morphology. Nano TMU-34(-2H), can detect phenylhydrazine
      (PH) by color changing from pink to deep purple. As a comparison, nano and
      crystal samples of TMU-34(-2H) were treated to detect PH. Experiments show that
      nano TMU-34(-2H) has better detection limit and response time.

PMID- 28427663
TI  - Fast sono assisted ferrofluid mediated silver super - Adsorption over magnesium
      ferrite-copper sulfide chalcogenide with the aid of multivariate optimization.
AB  - This research focuses on the development of a fast ultrasonic assisted ferrofluid
      mediated methodology to obtain the optimum conditions for silver adsorption from
      aqueous solutions. For this purpose magnesium ferrite-copper sulfide chalcogenide
      was synthesized and employed as an efficient nanosorbent. The sorbent was
      characterized with energy-dispersive X-ray spectroscopy (EDX), field emission
      scanning electron microscopy (FE-SEM), X-ray powder diffraction (XRD) and
      vibrational sample magnetometry (VSM) techniques. For obtaining the optimal
      operating conditions of silver adsorption, response surface methodology (RSM) was
      used. Tests were performed by Box-Behnken design (BBD). The value of optimum
      conditions for silver adsorption include pH=2.5, adsorbent dosage=10.0mg,
      sonicating time=1min and ionic strength=2.2%. According optimum conditions,
      percentage of removal should be 99.34%. With replication of similar experiment
      (n=6) average percentage of 100+/-0.95% was obtained for Ag+ adsorption which
      shows good agreement between predicted and experimental results. Silver ion
      adsorption follow Langmuir model with maximum sorption capacity of 2113mgg-1.
      Ultrasonic power helped to prepare ferrofluid and demonstrated that had an
      important role in better dispersing of it in solution and efficient adsorption of
      analyte.

PMID- 28427664
TI  - Ultrasonic irradiation of low intensity with a mode of sweeping frequency
      enhances the membrane permeability and cell growth rate of Candida tropicalis.
AB  - Here we report the enhancement of both cellular permeability and cell growth rate
      of Candida tropicalis after treatment with the ultrasonic irradiation of low
      intensity using a mode of sweeping frequency (UILS) generated by a self-developed
      ultrasonic device in our lab. After the ultrasonic treatment, remarkable biomass
      enhancement of the yeast was observed; the hyphae became significantly longer;
      the seeped cellular protein and nucleic acid from the yeast increased and the
      cellular Ca2+ content became lower. Illumina transcriptome sequencing showed that
      the ultrasonic treatment affected the expression of genes involved in diverse
      cellular components, biological processes and molecular functions. RT-PCR and
      Western blotting further confirmed the up-/down-regulation of genes in the
      ultrasound-treated yeasts. The optimal conditions of the ultrasonic treatment for
      the maximum biomass addition were determined as follows: the yeast was treated
      for 1h at the mid logarithmic phase, the frequency was 28+/-2kHz and the power
      density was 120W/L. Under these conditions, the Candida tropicalis biomass
      increased by 142.5% compared with the untreated yeast.

PMID- 28427665
TI  - Combined ultrasonic and gamma-irradiation to prepare TiO2@PET-g-PAAc fabric
      composite for self-cleaning application.
AB  - The grafting of polyacrylic acid (PAAc) onto the fabric of
      Poly(ethyleneterephthalate) (PET) was loaded with TiO2 by a mixture sonication of
      TiO2 dispersed in AAc dissolved in acetone solvent. Ultrasonic irradiation was
      utilized as a tool for a good dispersion of TiO2 onto the PET fabric. The grafted
      PET fabrics with acrylic acid AAc monomer were successfully obtained using gamma
      ray induced graft polymerization, the degree of grafting PET-g-PAAc fiber was
      105%. The chemical compositions and crystal structure of grafted TiO2@PET-g-PAAc
      fabrics were characterized by ATR-FTIR and XRD. It was found that loading of PET
      fiber with in TiO2 particles showing the formation of anatase and rutile as
      performed by XRD. The thermal property of TiO2@PET-g-PAAc was investigated by
      differential thermal analysis (DTA). The obtained result indicated the thermal
      property of the grafted TiO2@PET-g-PAAc was increased. Image of scanning electron
      microscope (SEM) indicated the good adherent and good distribution of PAAc and
      TiO2 with PET fabric. The self-cleaning property of TiO2@PET-g-PAAc has been
      evaluated by using three kinds of dyes as models.

PMID- 28427666
TI  - The development of recent high-power ultrasonic transducers for Near-well
      ultrasonic processing technology.
AB  - With the reduction of crude oil throughout the world, enhance oil recovery
      technology has become a major oil research topics, which can greatly increase the
      recovery ratio of the crude oil before the dawning of renewable energy era. Near
      well ultrasonic processing technology, as one new method, has attracted more
      attention for Enhanced Oil Recovery due to its low cost, good applicability and
      no environmental pollution in recent rears. There are two important relevant
      aspects about Near-well ultrasonic processing technology: (a) how to enhance the
      oil flow through the rocks into the pumping pool and (b) how to reduce the oil
      viscosity so that it can be easier to pump. Therefore, how to design a high-power
      ultrasonic equipment with excellent performance is crucial for Near-well
      ultrasonic processing technology. In this paper, recent new high-power ultrasonic
      transducers for Near-well ultrasonic processing technology are summarized. Each
      field application of them are also given. The purpose of this paper is to provide
      reference for the further development of Near-well ultrasonic processing
      technology. With the reduction of crude oil throughout the world, enhance oil
      recovery technology has become a major oil research topics, which can greatly
      increase the recovery ratio of the crude oil before the dawning of renewable
      energy era. Near-well ultrasonic processing technology, as one new method, has
      attracted more attention for Enhanced Oil Recovery due to its low cost, good
      applicability and no environmental pollution in recent rears. There are two
      important relevant aspects about Near-well ultrasonic processing technology: (a)
      how to enhance the oil flow through the rocks into the pumping pool and (b) how
      to reduce the oil viscosity so that it can be easier to pump. Therefore, how to
      design a high-power ultrasonic equipment with excellent performance is crucial
      for Near-well ultrasonic processing technology. In this paper, recent new high
      power ultrasonic transducers for Near-well ultrasonic processing technology are
      summarized. Each field application of them are also given. The purpose of this
      paper is to provide reference for the further development of Near-well ultrasonic
      processing technology.

PMID- 28427667
TI  - Membrane cleaning with ultrasonically driven bubbles.
AB  - A laboratory filtration plant for drinking water treatment is constructed to
      study the conditions for purely mechanical in situ cleaning of fouled polymeric
      membranes by the application of ultrasound. The filtration is done by suction of
      water with defined constant contamination through a membrane module, a stack of
      five pairs of flat-sheet ultrafiltration membranes. The short cleaning cycle to
      remove the cake layer from the membranes includes backwashing, the application of
      ultrasound and air flushing. A special geometry for sound irradiation of the
      membranes parallel to their surfaces is chosen. Two frequencies, 35kHz and
      130kHz, and different driving powers are tested for their cleaning effectiveness.
      No cleaning is found for 35kHz, whereas good cleaning results are obtained for
      130kHz, with an optimum cleaning effectiveness at moderate driving powers.
      Acoustic and optic measurements in space and time as well as analytical
      considerations and numerical calculations reveal the reasons and confirm the
      experimental results. The sound field is measured in high resolution and bubble
      structures are high-speed imaged on their nucleation sites as well as during
      their cleaning work at the membrane surface. The microscopic inspection of the
      membrane surface after cleaning shows distinct cleaning types in the cake layer
      that are related to specific bubble behaviour on the membrane. The membrane
      integrity and permeate quality are checked on-line by particle counting and
      turbidity measurement of the permeate. No signs of membrane damage or
      irreversible membrane degradation in permeability are detected and an excellent
      water permeate quality is retained.

PMID- 28427668
TI  - Synthesis of hydroxyapatite nanorods for application in water defluoridation and
      optimization of process variables: Advantage of ultrasonication with
      precipitation method over conventional method.
AB  - This research work presents the synthesis of hydroxyapatite (Hap) nanorods for
      defluoridation of drinking water by using both conventional (CM) and
      ultrasonication with precipitation (USPM) methods. Calcium nitrate was reacted
      with potassium phosphate in presence of ammonia for controlled pH to synthesize
      Hap nanorods, which was characterized using FTIR, XRD, SEM, TG-DTA, and TEM/EDS
      for determining its phase composition, structural and thermal decomposition
      behavior. When USPM method was used for synthesis, the yield of the Hap nanorods
      was improved from 83.24+/-1.0% to 90.2+/-1.0%, and complete phase transformation
      occurred with formation of elongated Hap nanorods. Effects of process parameters
      such as solution pH, contact time and adsorbent dose were studied through
      response surface methodology (RSM). A simple quadratic model was developed using
      Central Composite Design (CCD) and optimum parameters for fluoride adsorption
      process were determined to be pH 7, contact time 3h and adsorbent dose 7g/L for
      maximum removal capacity. Fluoride removal efficiency was predicted to be 93.64%
      which was very close to the experimental value obtained at 92.86% using
      ultrasonically prepared Hap. Fluoride adsorption isotherms fitted the Freundlich
      isotherm with an adsorption capacity of 1.49mg/g, while the kinetic studies
      revealed that the process followed pseudo-second order model. The treated water
      quality parameters such as residual fluoride, calcium leached, total hardness and
      alkalinity was investigated, and it was observed that all these parameters were
      within the permissible limits as per WHO and BIS standards.

PMID- 28427669
TI  - Rapid Ag/Sn/Ag transient liquid phase bonding for high-temperature power devices
      packaging by the assistance of ultrasound.
AB  - Rapid transient liquid phase (TLP) bonding process on Ag/Sn/Ag system is achieved
      in air by the assistance of ultrasonic, which has great potential to be applied
      to high-temperature power devices packaging. In this study, the influence of
      ultrasonic effect on the morphology and growth kinetics of Ag3Sn grains, and the
      joint microstructure, mechanical property and thermal reliability were
      systematically investigated. Experimental results indicated that the rapid
      consumption of the "dynamic" transient liquid phase was attributed to the
      accelerated dissolution of Ag substrate and the extrusion of liquid Sn, which
      were entirely induced by the complex sonochemical effects on the liquid/solid
      intermetallic compounds (IMCs) interface. An elongated scallop-like morphology of
      Ag3Sn grains was developed during Ag/Sn interfacial reaction with ultrasonic,
      accompanied by widening of grooves between neighbored grains. This phenomenon is
      called as a strengthening thermal grooving, in which the grooves at grain
      boundaries provide stable molten channels for Ag atoms diffusion from the
      substrate. Consequently, the improved elemental diffusion was evaluated through
      the growth kinetics of Ag3Sn IMCs, with conservative estimation of 6-16.5 times
      faster than the traditional TLP process. In addition, both excellent mechanical
      property and thermal reliability of the Ag-Sn intermetallic joint were
      experimentally verified by shear test and high-temperature storage test,
      respectively.

PMID- 28427670
TI  - Estimation of the distribution of low-intensity ultrasound mechanical index as a
      parameter affecting the proliferation of spermatogonia stem cells in vitro.
AB  - Considering the use of physical and mechanical stimulation, such as low-intensity
      ultrasound for proliferation and differentiation of stem cells, it is essential
      to understand the physical and acoustical mechanisms of acoustic waves in vitro.
      Mechanical index is used for quantifying acoustic cavitation and the relationship
      between acoustic pressure and the frequency. In this study, modeling of the
      mechanical index was applied to provide treatment protocol and to understand the
      effective physical processes on reproducibility of stem cells. Due to low
      intensity of ultrasound, Rayleigh integral model has been used for acoustic
      pressure computation. The acoustic pressure and mechanical index equations are
      modeled and solved to estimate optimal mechanical index for 28, 40, 150kHz and
      1MHz frequencies. This model are solved in different intensities and distances
      from transducer in cylindrical coordinates. Based on the results of the
      mechanical index, regions with threshold mechanical index of 0.7 were identified
      for extracting of radiation arrangement to cell medium. Acoustic pressure
      distribution along the axial and radial was extracted. In order to validate the
      results of the modeling, the acoustic pressure in the water and near field depth
      was measured by a piston hydrophone. Results of modeling and experiments show
      that the model is consistent well to experimental results with 0.91 and 0.90
      correlation of coefficient (p<0.05) for 1MHz and 40kHz. Low-intensity ultrasound
      with 0.40 mechanical index is more effective on enhancing the proliferation rate
      of the spermatogonia stem cells during the seven days of culture. In contrast,
      higher mechanical index has a harmful effect on the spermatogonial stem cells.
      Thus, considering cavitation threshold of different materials is necessary to
      find effective mechanical index ranges on proliferation for the used frequencies.
      This acoustic propagation model and ultrasound mechanical index assessments can
      be used with acceptable accuracy, for the extraction special arrangement of
      acoustic exposure used in biological conditions in vitro. This model provides
      proper treatment planning in vitro and in vivo by estimating the cavitation
      phenomenon.

PMID- 28427672
TI  - Current status and future perspectives of sonodynamic therapy in glioma
      treatment.
AB  - Malignant glioma is one of the most challenging central nervous system diseases
      to treat, and has high rates of recurrence and mortality. The current therapies
      include surgery, radiation therapy, and chemotherapy, although these approaches
      often failed to control tumor progression or improve patient survival.
      Sonodynamic therapy is a developing cancer treatment that uses ultrasound
      combined with a sonosensitizer to synergistically kill tumor cells, and has
      provided impressive results in both in vitro and in vivo studies. The ultrasound
      waves can penetrate deep tissues and reversibly open the blood-brain barrier to
      enhance drug delivery to the brain. Thus, sonodynamic therapy has a promising
      potential in glioma treatment. In this review, we summarize the studies that have
      confirmed the pre-clinical efficacy of sonodynamic therapy for glioma treatment,
      and discuss the future directions for this emerging treatment.

PMID- 28427671
TI  - Ultrasound-assisted rapid extraction and kinetic modelling of influential
      factors: Extraction of camptothecin from Nothapodytes nimmoniana plant.
AB  - Ultrasound-assisted extraction (UAE) of commercially important natural product
      camptothecin (CPT) from Nothapodytes nimmoniana plant has been investigated. The
      influences of process factors such as electric acoustic intensity, solid to
      liquid ratio, duty cycle, temperature and particle size on the maximum extraction
      yield and kinetic mechanisms of the entire extraction process have been
      investigated. The kinetics results showed that increasing the intensity, duty
      cycle, solid to liquid ratio and decreasing the particle size lead to substantial
      increase in extraction yields compared to classical stirring extraction.
      Different kinetic models were applied to fit the experimental data. The second
      order rate model appears to be the best. The extraction rate constant, initial
      extraction rate and the equilibrium concentration for all experimental conditions
      have been calculated. SEM analysis of spent plant material clearly showed hollow
      openings on cell structure, which could be directly correlated to explosive
      disruption by the action of ultrasound waves. Overall 1.7-fold increase in
      extraction yields of CPT (0.32% w/w) and decrease in time from 6h to 18min was
      observed over the stirring method.

PMID- 28427673
TI  - Sonocatalytic rapid degradation of Congo red dye from aqueous solution using
      magnetic Fe0/polyaniline nanofibers.
AB  - Nano-sized magnetic Fe0/polyaniline (Fe0/PANI) nanofibers were used as an
      effective material for sonocatalytic degradation of organic anionic Congo red
      (CR) dye. Fe0/PANI, was synthesized via reductive deposition of nano-Fe0 onto the
      PANI nanofibers at room temperature. Prepared catalyst was characterized using HR
      TEM, FE-SEM, XRD, FTIR instruments. The efficacy of catalyst in removing CR was
      assessed colorimetrically using UV-visible spectroscopy under different
      experimental conditions such as % of Fe0 loading into the composite material,
      solution pH, initial concentration of dye, catalyst dosage, temperature and
      ultrasonic power. The optimum conditions for sonocatalytic degradation of CR were
      obtained at catalyst concentrations=500mg.L-1, concentration of CR=200ppm,
      solution pH=neutral (7.0), temperature=30 degrees C, % of Fe0 loading=30% and
      500W ultrasonic power. The experimental results showed that ultrasonic process
      could remove 98% of Congo red within 30min with higher Qmax value (Qmax=446.4 at
      25 degrees C). The rate of degradation of CR dye was much faster in this
      ultrasonic technique rather than conventional adsorption process. The degradation
      efficiency declined with the addition of common inorganic salts (NaCl, Na2CO3,
      Na2SO4 and Na3PO4). The rate of degradation suppressed more with increasing salt
      concentration. Kinetic and isotherm studies indicated that the degradation of CR
      provides pseudo-second order rate kinetic and Langmuir isotherm model compared to
      all other models tested. The excellent high degradation capacity of Fe0/PANI
      under ultrasonic irradiation can be explained on the basis of the formation of
      active hydroxyl radicals (OH) and subsequently a series of free radical
      reactions.

PMID- 28427674
TI  - Sonochemical synthesis and characterization of new nanostructures cobalt(II)
      metal-organic complexes derived from the azo-coupling reaction of 4-amino benzoic
      acid with anthranilic acid, salicylaldehyde and 2-naphtol.
AB  - Nanostructures of three new cobalt(II) complexes, (CoL1).0.5DMF.1.5MeOH (1),
      [H2L1=5-(4-Carboxy phenyl azo) anthranilic acid], (Co(L2)2).1.5MeOH (2), [HL2=5
      (4-Carboxy phenyl azo) salicylaldehyde] and (Co(L3)2).0.5DMF.0.5MeOH (3), [HL3=1
      (4-Carboxy phenyl azo) 2-naphtol], have been synthesized by the reaction of H2L1,
      HL2 and HL3 with Co(OAc)2.4H2O through sonochemical process. Calcination of the
      nano-sized compounds 1-3 yield Co3O4 nanoparticles at 450 degrees C under air
      atmosphere. These nanostructures were characterized by X-ray powder diffraction
      (XRD) and Scanning Electron Microscopy (SEM). Thermal stability of compounds 1-3
      was studied by thermogravimetric (TG) and differential thermal analyses (DTA).

PMID- 28427675
TI  - Use of PVA/alpha-MnO2-stearic acid nanocomposite films prepared by sonochemical
      method as a potential sorbent for adsorption of Cd (II) ion from aqueous
      solution.
AB  - Alpha manganese dioxide (alpha-MnO2) nanorods have been covalently functionalized
      with stearic acid by solvothermal method. The alpha-MnO2-stearic acid nanorods
      were characterized by Fourier transform infrared spectroscopy, X-ray diffraction,
      field emission scanning electron microscopy and transmission electron microscopy.
      The amount of stearic acid grafted onto alpha-MnO2 surface was determined about
      41wt% by thermogravimetric analysis. The alpha-MnO2-stearic acid nanorods was
      used as nanofiller for the preparation of poly(vinyl alcohol) (PVA)
      nanocomposites (NCs). The NCs with 1, 3, and 5wt% of nanofiller were prepared
      through ultrasound assisted technique as an economical, fast, eco-friendly, and
      effective method. The PVA/alpha-MnO2-stearic acid NCs were characterized by
      different techniques. The results showed that with increasing the alpha-MnO2
      stearic acid content, the thermal stability and tensile properties were improved.
      Besides, the NC 5wt% was used as adsorbent for sorption of Cd (II) ion. The
      adsorption efficiency of NC 5wt% in different initial concentrations of Cd (II)
      ion (20-100mgL-1) was 58-95%. All the isotherm data were well fitted by both
      Langmuir and Freundlich equations. The adsorption kinetics study demonstrated
      that pseudo-second-order model was the best fit with the experimental data. The
      results indicated that prepared NCs are promising adsorbents for the removal of
      Cd (II) ion from the aqueous solution.

PMID- 28427676
TI  - Ultrasonic-assisted reactive-extraction is a fast and easy method for biodiesel
      production from Jatropha curcas oilseeds.
AB  - The alkyl ester of vegetable oil represents as an alternative fuel for diesel
      engines which is to reduce the cost of biodiesel by increasing the efficiency of
      biodiesel production by single step reaction i.e. production of biodiesel by
      combing extraction of oil from oilseed and reaction of extract with alcohol by
      using ultrasonication. This process is called ultrasonic reactive-extraction. It
      consists of the investigation of the optimum conditions i.e. seed size >1-<2,
      molar ratio oilseed to methanol 1:100, catalyst concentration 1.5wt% of oilseed,
      reaction time 20min and ultrasonic amplitude 50%, cycle 0.3s gives the maximum
      conversion.

PMID- 28427677
TI  - Ultrasonic hot powder compaction of Ti-6Al-4V.
AB  - Power ultrasonic has been recently employed in a wide variety of manufacturing
      processes among which ultrasonic assisted powder compaction is a promising powder
      materials processing technique with significant industrial applications. The
      products manufactured by the powder metallurgy commonly consist of residual
      porosities, material impurities, structural non-homogeneities and residual
      stress. In this paper, it is aimed to apply power ultrasonic to the hot
      consolidation process of Ti-6Al-4V titanium alloy powder in order to improve
      mechanical properties. To do this, the effects of ultrasonic power and process
      temperature and pressure were considered and then deeply studied through a series
      of experiments. It was shown that the addition of ultrasonic vibration leads to a
      significant improvement in the consolidation performance and the mechanical
      strength of the fabricated specimens.

PMID- 28427678
TI  - Application and mechanism of ultrasonic static mixer in heavy oil viscosity
      reduction.
AB  - In the present study, heavy oil viscosity reduction in Daqing oil field was
      investigated by using an ultrasonic static mixer. The influence of the ultrasonic
      power on the viscosity reduction rate was investigated and the optimal
      technological conditions were determined for the ultrasonic treatment. The
      mechanism for ultrasonic viscosity reduction was analyzed. The flow
      characteristics of heavy oil in the mixer under the effect of cavitation were
      investigated using numerical modeling, and energy consumptions were calculated
      during the ultrasonic treatment and vis-breaking processes. The experimental
      results indicated that the ultrasonic power made the largest impact on the
      viscosity reduction rate, followed by the reaction time and temperature. The
      highest viscosity reduction rate was 57.34%. Vacuole was migrated from the axis
      to the wall along the fluid, accelerating the two-phase transmission and
      enhancing the radial flow of the fluid, which significantly improved the
      ultrasonic viscosity reduction. Compared to the vis-breaking process, the energy
      consumption of ultrasonic treatment process was 43.03% lower when dealing with
      the same quality heavy oil. The optimal process conditions were found to be as
      follows: ultrasonic power of 1.8kW, reaction time of 45min and reaction
      temperature of 360 degrees C. The dissociation of the molecules of heavy oil
      after ultrasonication has been checked. After being kept at room temperature
      12days, some light components were produced by the cavitation cracking, so the
      viscosity of the residual oil could not return to that of the original residual
      oil, which meant that the "cage effect" was not reformed.

PMID- 28427679
TI  - Sonochemical synthesis and characterization of microrod to nanoparticle of new
      mixed-ligand zinc(II) fumarate metal-organic polymer.
AB  - Micro and nano-structures of a new mixed-ligand Zn(II) fumarate metal-organic
      polymer, {[Zn(tptz)(fum)].DMF}n (1), (tptz=2,4,6-tris(2-pyridyl)-s-triazine,
      fum=fumarate, DMF=N,N-dimethylforamide), were synthesized by sonochemical method.
      These new micro and nano-structures were characterized by scanning electron
      microscopy (SEM), X-ray diffraction (XRD), IR spectroscopy and elemental
      analyses. Compound 1 was structurally characterized by single-crystal X-ray
      diffraction and consists of the primary unit of [Zn(tptz)(fum)]. Self assembly
      between the units of [Zn(tptz)(fum)] from Zn-O bonds results in the formation of
      a one-dimensional zinc(II) coordination polymer. The ZnII-ion in compound 1 has
      ZnO2N3 coordination sphere with a trigonal bipyramidal molecular geometry.
      Compound 1 was synthesized by ultrasound irradiation under different
      concentrations and times. The microrods structure of compound 1 with increasing
      of concentration and ultrasound radiation time were synthesized as nanoparticles
      structure successfully. So ultrasound radiation change morphology from microrods
      to nanoparticles.

PMID- 28427680
TI  - Numerical modelling of ultrasonic waves in a bubbly Newtonian liquid using a high
      order acoustic cavitation model.
AB  - To address difficulties in treating large volumes of liquid metal with
      ultrasound, a fundamental study of acoustic cavitation in liquid aluminium,
      expressed in an experimentally validated numerical model, is presented in this
      paper. To improve the understanding of the cavitation process, a non-linear
      acoustic model is validated against reference water pressure measurements from
      acoustic waves produced by an immersed horn. A high-order method is used to
      discretize the wave equation in both space and time. These discretized equations
      are coupled to the Rayleigh-Plesset equation using two different time scales to
      couple the bubble and flow scales, resulting in a stable, fast, and reasonably
      accurate method for the prediction of acoustic pressures in cavitating liquids.
      This method is then applied to the context of treatment of liquid aluminium,
      where it predicts that the most intense cavitation activity is localised below
      the vibrating horn and estimates the acoustic decay below the sonotrode with
      reasonable qualitative agreement with experimental data.

PMID- 28427681
TI  - Sonochemical assisted synthesis of RGO/ZnO nanowire arrays for
      photoelectrochemical water splitting.
AB  - This article presented the synthesis of a hybrid nanoarchitecture material
      composed of reduced graphene oxide (RGO) multiple sheets and ZnO nanowire arrays
      (NWAs) formed on an arbitrary ZnO coated fluorine doped tin oxide (FTO)
      substrates via pulse sonication and hydrothermal approach. The NWAs have high
      aspect-ratio, high density, apt positioning and well-ordered formation. FESEM
      images demonstrated that RGO layers have been effectively intercalated between
      and on the accessible surfaces of the ZnO NWAs. The diameter of ZnO nanowires is
      80-150nm and length about 1-2MUm. Raman spectrum of hybrid material exhibited
      characteristic D and suppressed G peaks for graphene and E2 mode at 437cm-1 for
      ZnO NWAs. UV-visible spectrum indicated slight red shift towards visible range
      after formation of RGO/ZnO NWAs heterostructure. The Photoelectrochemical results
      indicated higher current densities for RGO/ZnO NWAs heterostructure due to water
      oxidation reaction at the working electrode compared to pristine ZnO NWAs.

PMID- 28427682
TI  - Effects and mechanism of diclofenac degradation in aqueous solution by US/Zn0.
AB  - A system of ultrasound radiation coupled with Zn0 was applied to degrade
      diclofenac. The effects of initial pH, dosage of Zn0 and ultrasound density were
      investigated. To further explore the mechanism of the microcosmic reaction, the
      fresh and used Zn0 powders were characterized by SEM, XRD and XPS. Radical
      scavengers were used to determine the oxidation performance of strong oxidizing
      free radicals on diclofenac, including hydroxyl radicals and superoxide radicals.
      The results showed that the optimum removal of diclofenac reached to over 85% at
      pH of 2.0 in 15min, with Zn0 dosage of 0.1g/L and ultrasound density of 0.6W/cm3.
      TOC removal of 72.6% in 15min and dechlorination efficiency of diclofenac reached
      70% in 30min. Characterization results showed that a ZnO membrane was generated
      on the surface of Zn particles after use. According to the mass spectrometry
      results, several possible pathways of diclofenac degradation were proposed, and
      most diclofenac was turned into micro-molecules or CO2 finally. The synergistic
      effect of US/Zn0 in the reactions led to a proposed degradation mechanism in
      which zinc could directly attack the target contaminant diclofenac because of its
      good reducibility with the auxiliary functions of ultrasonic irradiation,
      mechanical shearing and free radical oxidation.

PMID- 28427684
TI  - Rapid and high-capacity ultrasonic assisted adsorption of ternary toxic anionic
      dyes onto MOF-5-activated carbon: Artificial neural networks, partial least
      squares, desirability function and isotherm and kinetic study.
AB  - The present paper focused on the ultrasonic assisted simultaneous removal of fast
      green (FG), eosin Y (EY) and quinine yellow (QY) from aqueous media following
      using MOF-5 as a metal organic framework and activated carbon hybrid (AC-MOF-5).
      The structure and morphology of AC-MOF-5 was identified by SEM, FTIR and XRD
      analysis. The interactive and main effects of variables such as pH, initial dyes
      concentration (mgL-1), adsorbent dosage (mg) and sonication time (min) on removal
      percentage were studied by central composite design (CCD), subsequent
      desirability function (DF) permit to achieved real variable experimental
      condition. Optimized values were found 7.06, 5.68, 7.59 and 5.04mgL-1, 0.02g and
      2.55min for pH, FG, EY and QY concentration, adsorbent dosage and sonication
      time, respectively. Under this conditions removal percentage were obtained 98.1%,
      98.1% and 91.91% for FG, EY and QY, respectively. Two models, namely partial
      least squares (PLS) and multi-layer artificial neural network (ANN) model were
      used for building up to construct an empirical model to predict the dyes under
      study removal behavior. The obtained results show that ANN and PLS model is a
      powerful tool for prediction of under-study dyes adsorption by AC-MOF-5. The
      evaluation and estimation of equilibrium data from traditional isotherm models
      display that the Langmuir model indicated the best fit to the equilibrium data
      with maximum adsorption capacity of 21.230, 20.242 and 18.621mgg-1, for FG, EY
      and QY, respectively, while the adsorption rate efficiently follows the pseudo
      second-order model.

PMID- 28427685
TI  - Fe3O4/hydroxyapatite/graphene quantum dots as a novel nano-sorbent for
      preconcentration of copper residue in Thai food ingredients: Optimization of
      ultrasound-assisted magnetic solid phase extraction.
AB  - Fe3O4/hydroxyapatite/graphene quantum dots (Fe3O4/HAP/GQDs) nanocomposite was
      synthesized and used as a novel magnetic adsorbent. This nanocomposite was
      characterized using scanning electron microscopy, transmission electron
      microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, energy
      dispersive X-ray spectroscopy, and magnetization property. The Fe3O4/HAP/GQDs was
      applied to pre-concentrate copper residues in Thai food ingredients (so-called
      "Tom Yum Kung") prior to determination by inductively coupled plasma-atomic
      emission spectrometry. Based on ultrasound-assisted extraction optimization,
      various parameters affecting the magnetic solid-phase extraction, such as
      solution pH, amount of magnetic nanoparticles, adsorption and desorption time,
      and type of elution solvent and its concentration were evaluated. Under optimal
      conditions, the linear range was 0.05-1500ngmL-1 (R2>0.999), limit of detection
      was 0.58ngmL-1, and limit of quantification was 1.94ngmL-1. The precision,
      expressed as the relative standard deviation of the calibration curve slope
      (n=5), for intra-day and inter-day analyses was 0.87% and 4.47%, respectively.
      The recovery study of Cu for real samples was ranged between 83.5% and 104.8%.
      This approach gave the enrichment factor of 39.2, which guarantees trace analysis
      of Cu residues. Therefore, Fe3O4/HAP/GQDs can be a potential and suitable
      candidate for the pre-concentration and separation of Cu from food samples. It
      can easily be reused after treatment with deionized water.

PMID- 28427686
TI  - Ultrasound assisted acid catalyzed lactose hydrolysis: Understanding into effect
      of operating parameters and scale up studies.
AB  - The current work deals with the value addition of lactose by transforming into
      hydrolyzed lactose syrup containing glucose and galactose in major proportion
      using the novel approach of ultrasound assisted acid catalyzed lactose
      hydrolysis. The hydrolysis of lactose was performed in ultrasonic bath (33kHz) at
      50% duty cycle at different temperatures as 65 degrees C and 70 degrees C and two
      different hydrochloric acid (HCl) concentrations as 2.5N and 3N. It was observed
      that acid concentration, temperature and ultrasonic treatment were the major
      factors in deciding the time required to achieve ~90% hydrolysis. The ultrasonic
      assisted approach resulted in reduction in the reaction time and the extent of
      intensification was established to be dependent on the temperature, acid
      concentration and time of ultrasonic exposure. It was observed that the maximum
      process intensification obtained by introduction of ultrasound in the lactose
      hydrolysis process performed at 70 degrees C and 3N HCl was reduction in the
      required time for ~90% hydrolysis from 4h (without the presence of ultrasound) to
      3h. The scale-up study was also performed using an ultrasonic bath with
      longitudinal horn (36kHz as operating frequency) at 50% duty cycle, optimized
      temperature of 70 degrees C and acid concentration of 3N. It was observed that
      the reaction was faster in the presence of ultrasound and stirring by axial
      impeller at rpm of 225+/-25. The time required to complete ~90% of hydrolysis
      remained almost the same as observed for small scale study on ultrasonic bath
      (33kHz) at 50% duty cycle. The use of recovered lactose from whey samples instead
      of pure lactose did not result in any significant changes in the progress of
      hydrolysis, confirming the efficacy of the selected approach. Overall, the work
      has presented a novel ultrasound assisted approach for intensified lactose
      hydrolysis.

PMID- 28427687
TI  - Improved adsorption performance of nanostructured composite by ultrasonic wave:
      Optimization through response surface methodology, isotherm and kinetic studies.
AB  - In this work, ultrasound-assisted adsorption of an anionic dye, sunset yellow
      (SY) and cationic dyes, malachite green (MG), methylene blue (MB) and their
      ternary dye solutions onto Cu@ Mn-ZnS-NPs-AC from water aqueous was optimized by
      response surface methodology (RSM) using the central composite design (CCD). The
      adsorbent was characterized using Field emission scanning electron microscopy
      (FESEM), X-ray diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDX) and
      EDX mapping images. The effects of various parameters such as pH, sonication
      time, adsorbent mass and initial concentrations of SY, MG and MB were examined. A
      total 33 experiments were conducted to establish a quadratic model. Cu@ Mn-ZnS
      NPs-AC has the maximum adsorption efficiency (>99.5%) when the pH, sonication
      time, adsorbent mass and initial concentrations of SY, MG and MB were optimally
      set as 6.0, 5min, 0.02g, 9, 12 and 12mgL-1, respectively. Sonication time has a
      statistically significant effect on the selected responses. Langmuir isotherm
      model was found to be best fitted to adsorption and adsorption capacities were
      67.5mgg-1 for SY, 74.6mgg-1 for MG and 72.9mgg-1 for MB. Four kinetic models
      (pseudo-first order, pseudo-second order, Weber-Morris intraparticle diffusion
      rate and Elovich) were tested to correlate the experimental data and the sorption
      was fitted well with the pseudo-second order kinetic model.

PMID- 28427688
TI  - Pruritus may be a common symptom related to neuromyelitis optica spectrum
      disorders.
AB  - BACKGROUND: To evaluate pruritus in patients with neuromyelitis optica spectrum
      disorders (NMOSD) and to characterize the relationship between pruritus and
      lesions of NMOSD. METHODS: 61 patients with NMOSD were included in the study and
      their medical records were reviewed for pruritus, neurological symptoms and
      magnetic resonance imaging (MRI) images. We focused on the patients' history of
      pruritus, especially the severity, duration, region, and the relationship of
      pruritus with other symptoms of NMOSD. RESULTS: Of the 61 patients with NMOSD, 59
      had longitudinally extensive transverse myelitis (LETM). 38 of these patients
      (64.4%) reported pruritus during the course of their illness, with 16 patients
      reporting pruritus as the initial symptoms followed by limb weakness. In 35 of 38
      patients (92.1%), pruritus was located within the dermatomes innervated by the
      spinal nerves from the involved spinal cord. CONCLUSION: Our results show that
      pruritus is a common symptom of NMOSD and relates to the lesions in the spinal
      cord. Pruritus may indicate a new episode of myelitis in patients with NMOSD.

PMID- 28427689
TI  - Demographic and clinical profile of Multiple Sclerosis in Kashmir: A short
      report.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune and inflammatory
      disease of the central nervous system (CNS). There have been only few
      population/hospital based studies on MS in India, and at the same time there is
      no data on its profile in Kashmir. METHODS: A total of 41 MS patients diagnosed
      on the basis of 2010 Revised Mc Donald criteria were enrolled in this study from
      Kashmir region of India. Clinical, demographic, radiological and biochemical
      parameters were analyzed for most of the patients. RESULTS: Male to female ratio
      was found to be 1:3.1 with mean age at the time of analysis 32.26+/-7.54 (range
      18-48) years. The mean disease duration was found to be 3.2+/-3.6 years. The most
      common course was relapsing-remitting (RR) present in 87.80% of cases followed by
      secondary progressive (SP) in 9.76% and primary progressive (PP) in 2.44%.
      Numbness, weakness of limbs, prickling and tingling sensations, muscle stiffness,
      and visual disturbances were most common manifestations. Condition of bilateral
      internuclear ophthalmoplegia (INO) and vertigo was rarely observed. Oligoclonal
      bands (OCB) were present in cerebrospinal fluid (CSF) of majority of the
      patients. Symptomatic and steroidal treatment mode was given to majority of the
      patients (92.68%) and only 7.32% patients were given disease modifying drug.
      CONCLUSION: This is the first preliminary report on MS profile in Kashmir. The
      high prevalence of female patients and RR course of MS, low prevalence of
      progressive cases, predominance of OCB positive cases, insignificant family
      history in all cases, predominance of cases with low socio-economic status, and
      high rate of less educated and unemployed cases are the most important findings.
      By and large MS pattern in Kashmir was found to be relatively similar to West and
      rest of the Asia. Larger comprehensive studies are mandatory to completely
      understand MS pattern in Kashmir. There is utmost requirement to maintain a local
      MS registry in Kashmir so as to get an idea about the actual number of persons
      suffering from the disease and compare the data with other regions of India.

PMID- 28427690
TI  - Factors associated with adherence to disease modifying therapy in multiple
      sclerosis: An observational survey from a referral center in Lithuania.
AB  - AIM OF THE STUDY: To investigate adherence to disease modifying therapy (DMT) in
      Lithuanian population of multiple sclerosis patients and factors associated to
      it. METHODS: Patients receiving one of the following DMT's: Interferon beta 1a
      (Rebif) 44 micrograms three times a week subdermally (s/c) or Interferon beta 1a
      (Avonex) 30 micrograms weekly intramuscularly (i/m), or Interferon beta 1b
      (Betaferon, Extavia) 250 micrograms once in two days s/c, or Glatiramer acetate
      (Copaxone) 20mg daily s/c, were presented with a questionnaire inquiring their
      demographic and clinical characteristics and adherence to treatment profile, as
      well as HAD scale and SF-36 questionnaire. Those who missed at least one dose of
      DMT during last three months were considered non-adherent. RESULTS: In total, 207
      patients were enrolled, 73 (35.3%) of them were non adherent during last three
      months. More patients with university education (p=0.004, chi2 =8.466 high
      school/vocational vs. university) as well as consuming >4 units/year of alcohol
      were non-adherent during last three months (p=0.005). Average score for anxiety
      (6.69+/-4.03 vs. 6.92+/-4.24) and depression (4.74+/-3.9 vs. 4.7+/-3.83) in HAD
      scale did not differ significantly between adherent and non-adherent groups. We
      did not find any significant difference in quality of life scores (SF-36 v.2)
      between the groups. No significant difference of adherence was found then
      comparing patients often suffering from drug side effects with those who
      experience rare or no side effects. In logistic regression model, patients
      consuming more than 4 alcohol units per year and patients with university
      education were more likely to miss at least one dose during last three months:
      2.121 (95% CI: 1.143-3.937, p=0.017) and 2.409 (95% CI: 1.260-4.642, p=0.008)
      times accordingly. Patients with better quality of life scores were slightly less
      likely to be non adherent (OR 0.997 (95% CI: 0.994-0.999), p=0.0017).
      CONCLUSIONS: One third of patients were non-adherent during last three months.
      Worse adherence rates were associated with higher education and higher alcohol
      consumption. Education, alcohol consumption and quality of life scores were found
      to be significant factors for predicting non-adherence. We found no associations
      between adherence and anxiety, depression, or drugs side effects.

PMID- 28427691
TI  - Spastic paretic hemifacial contracture as a presenting feature of multiple
      sclerosis.
AB  - BACKGROUND: Spastic paretic hemifacial contracture (SPHC) is characterized by
      sustained unilateral contraction of the facial muscles associated with mild
      ipsilateral facial paresis. Rarely described in the context of multiple sclerosis
      (MS), it has never been reported as presenting symptom of MS. CASE REPORTS: Two
      patients developed SPHC within the context of a clinically isolated syndrome
      suggestive of MS. EMG revealed continuous resting activity of irregularly firing
      motor unit potentials, associated with impaired recruitment upon voluntary
      contraction. SPHC remitted fully in both patients. CONCLUSIONS: SPHC, a rare but
      distinct clinical and EMG entity, can occasionally be the presenting feature of
      MS.

PMID- 28427692
TI  - Treatment-resistant neuromyelitis optica spectrum disorders associated with
      Toxocara canis infection: A case report.
AB  - A 53-year-old woman was admitted to the department of neurology in Tenri Hospital
      because of progressive thoracic myelitis a month after she had eaten uncooked
      bovine liver. A previous episode of right optic neuritis and a positive test for
      serum anti-aquaporin-4 antibodies indicated a diagnosis of neuromyelitis optica
      spectrum disorders. Although the patient initially recovered with the reduction
      of anti-aquaporin-4 antibodies during treatment with intravenous
      methylprednisolone infusion and plasma exchange, her neurological symptoms
      deteriorated soon after the completion of plasma exchange. Western blotting
      analysis detected anti-Toxocara canis antibodies in the serum; thus, the patient
      underwent oral albendazole treatment. This resulted in the alleviation of her
      symptoms. We therefore consider that rigorous investigation should be encouraged
      to detect rare pathogens including parasites in cases of treatment-resistant
      neuromyelitis optica spectrum disorders.

PMID- 28427693
TI  - A case of CD30+ ALK1- anaplastic large cell lymphoma resembling acute
      disseminated encephalomyelitis.
AB  - Central nervous system involvement is an uncommon complication of systemic non
      Hodgkin lymphomas. The majority of these cases concern B-cell lymphomas. We
      report a case of systemic T-cell anaplastic large cell lymphoma CD30+ ALK- with
      CNS involvement at the time of diagnosis and unusual MRI characteristics
      resembling acute disseminated encephalomyelitis.

PMID- 28427694
TI  - Gait pattern in patients with different multiple sclerosis phenotypes.
AB  - BACKGROUND: Gait pattern is frequently impaired in multiple sclerosis (MS),
      however gait characteristics in patients with different MS phenotypes have not
      been fully elucidated. METHODS: We analyzed spatio-temporal gait pattern
      characteristics in patients with relapsing-remitting (RR, n=52) and primary
      progressive (PP, n=18) MS in comparison with age-matched healthy controls (HC,
      n=40). All subjects performed a standardized simple walking task, a dual motor-
      motor task, a dual motor-mental task, and a triple combined motor-mental task at
      a GAITRite electronic walkway of 5.5m active area. We measured: cycle time (CT),
      stride length (SL), swing time (ST), double support time (DST), gait velocity
      (GV) and calculated symmetry index (SI) for CT, SL and ST. RESULTS: With each
      task performed, CT and DST in the total MS group were significantly longer while
      SL was significantly shorter and GV significantly lower than in HC. ST was
      similar in the total MS patient group and HC. In both MS patients and HC, CT and
      DST increased and SL and GV decreased over repeated assessments. Dual and triple
      tasks while walking influenced walking performance in both MS patients and HC.
      Although patients with PPMS differed significantly from those with RRMS in the
      majority of gait parameters, the subgroup analysis in patients matched for age
      and disability (Expanded Disability Status Scale Score -EDSS, 3.0-5.0) showed
      similar gait performance in RRMS and PPMS patients having the same level of
      disability, except for CT and ST- symmetry parameters that were more impaired in
      the PPMS group. The EDSS score correlated significantly with CT, DST, SL and GV,
      but no significant correlation was found with ST except at the triple combined
      motor-mental task. CONCLUSION: A disturbed gait pattern in MS patients with
      different MS phenotypes depends on disability and reflects a cognitive-motor
      interference.

PMID- 28427695
TI  - Paraneoplastic acute disseminated encephalomyelitis associated with multiple
      myeloma.
AB  - We describe a man recently diagnosed with multiple myeloma who presented with
      progressive spastic paraparesis, encephalopathy and multifocal MRI lesions with
      haemorrhage. Brain histopathology was consistent with acute disseminated
      encephalomyelitis (ADEM) with no new clinicoradiological findings on follow-up.
      This case emphasises the growing paraneoplastic spectrum, including non-classical
      but treatable disorders such as ADEM.

PMID- 28427696
TI  - Genetic burden of MS risk variants distinguish patients from healthy individuals
      but are not associated with disease activity.
AB  - Weighted genetic risk score (wGRS) was analysed for association with disease
      activity in more than 500 MS patients before and during interferon-beta
      treatment. The wGRS was higher in MS patients than in healthy controls when
      analysing eight HLA - and 109 non-HLA MS risk gene variants. No significant
      associations were observed between number of relapses prior to or during
      treatment with interferon-beta, both with and without HLA risk alleles included
      in the wGRS. In conclusion, among Danes the wGRS was higher in MS patients than
      controls but was not associated with the overall disease activity or response to
      treatment with interferon-beta.

PMID- 28427698
TI  - Novel functional polymorphism in IGF-1 gene associated with multiple sclerosis: A
      new insight to MS.
AB  - BACKGROUND: Interactions between several genes and environment may play a role in
      susceptibility to multiple sclerosis (MS). The IGF-1 plays a key role in
      proliferation, maintenance and survival of nerve cells. Therefore, we
      hypothesized that IGF-1 may be a target for prediction and control MS. We aimed
      to analysis IGF-1 gene promoter sequence, to investigate the effect of the single
      nucleotide variants on IGF-1 expression and its association with MS. METHODS: We
      enrolled 339 MS patients and 431 healthy controls. A specific region in IGF-1
      gene promoter was investigated by SSCP analysis. All samples were genotyped by
      SSP-PCR. In-vitro and in-vivo IGF-1 production was measured by ELISA assay. IGF-1
      expression in PBMCs was measured using real-time PCR. RESULTS: We identified a T
      to C single nucleotide substitution at position -1089 and a C to T at position 
      383 from transcription start site in the IGF-1 gene promoter. There was a
      significant association between MS and genotypes IGF-1(-383) C/T (p=0.001) and
      IGF-1(-383) C/C (p<0.001). There was also a significant association between IGF
      1(-383) allele C and MS (p=0.001). In-vitro and in-vivo IGF-1 level showed that
      IGF-1 production in samples with genotype IGF-1(-383) C/C significantly was less
      than T/T (p=0.004) but not T/C (p=0.220). CONCLUSION: According to IGF-1 roles in
      CNS and our results, this study suggests that low IGF-1 level may be associated
      with susceptibility to MS.

PMID- 28427697
TI  - Health-care disparities stemming from sexual orientation of Italian patients with
      Multiple Sclerosis: A cross-sectional web-based study.
AB  - Lesbian, gay, bisexual and transgender (LGBT) patients might experience unique
      difficulties and barriers to treatment of chronic diseases related to their
      sexual orientation. Thus, we investigated concerns experienced by LGBT patients
      with multiple sclerosis (MS). We conducted a web-based survey using a multi
      choice questionnaire published in an Italian social-network
      (www.smsocialnetwork.com) for MS patients. The survey investigated: socio
      demographic factors, lifestyle habits, MS-related health status and LGBT specific
      issues (e.g. friendliness to their sexual orientation and eventual homophobic
      behaviors in the MS Center). Among MS patients willing to use psychological
      services, LGBT patients were associated with a smaller number of psychological
      consultations, compared to heterosexuals (Coeff.=-0.449; p<0.001; 95%CI=-0.682 to
      -0.217). LGBT patients were more likely to change MS Center, compared to
      heterosexuals (OR=2.064; p=0.046; 95%CI=1.011-4.212). The number of MS Center
      changes was associated with MS Center friendliness (p=0.037; rho=-0.229) and with
      the occurrence of homophobic behaviors (p=0.036; rho=0.234). LGBT MS patients
      more frequently changed MS Center and had a reduced use of psychological
      services, compared to heterosexuals. The attitude towards LGBT MS patients might
      affect resource utilizations and LGBTs health status.

PMID- 28427699
TI  - People with MS are less physically active than healthy controls but as active as
      those with other chronic diseases: An updated meta-analysis.
AB  - BACKGROUND: There has been remarkable growth in research examining physical
      activity behavior (any bodily movement produced by skeletal muscle contraction
      that results in energy expenditure) among people living with multiple sclerosis
      (MS) over the past decade. The current meta-analysis quantified physical activity
      participation levels in persons with MS compared with non-diseased and other
      clinical populations. METHODS: We searched PUBMED, PsycINFO and Web of Science
      using the keywords physical activity, exercise, and physical fitness in
      conjunction with MS. We conducted a quantitative synthesis of the difference in
      physical activity participation levels among persons with MS compared with non
      diseased populations and other clinical populations and then examined moderators
      that might explain variation in the overall effect size (ES). RESULTS: 21 studies
      were included involving 5303 persons with MS and yielded a mean ES of -0.57 (95%
      CI=-0.76, 60.37). The weighted mean ES was heterogeneous (Q=443.811, df=31,
      p<0.001). The magnitude of the mean ES increased when comparing the MS population
      with non-diseased populations, but decreased when comparing MS with clinical
      populations. CONCLUSION: The cumulative evidence reinforces that persons with MS
      are less physically active than non-diseased, but not clinical populations, and
      this observation supports the need for new efforts on promoting physical activity
      across the MS community.

PMID- 28427700
TI  - Effects of functional electrical stimulation on gait in people with multiple
      sclerosis - A systematic review.
AB  - BACKGROUND: Functional electrical stimulation (FES) is commonly used to
      ameliorate gait deficits in patients with multiple sclerosis (PwMS). This review
      critically evaluates the literature describing the orthotic and therapeutic
      effects of FES on gait in PwMS. METHODS: The PubMed, CINAHL, and ProQuest
      databases were searched. Included were studies that evaluated therapeutic and/or
      orthotic effects of FES in PwMS with at least one outcome measure related to
      gait. Methodology was assessed using the Downs and Black checklist. RESULTS:
      Twelve relevant studies were reviewed. Their methodological quality ranged from
      14 to 21 of 28. Eleven studies reported the effects of peroneal stimulation. Most
      found a significant orthotic effect (measured during stimulation), mainly on
      walking speed. Only three assessed the therapeutic effect (carry-over), which was
      not significant. CONCLUSIONS: The evidence presented in this review suggests that
      FES has a positive orthotic effect on walking in PwMS. Yet, more robust trials
      are needed to substantiate this finding. Therapeutic efficacy of FES was not
      demonstrated, and almost all studies tested a single channel peroneal stimulator.
      Future studies involving FES technological innovations with advanced clinical
      approaches might contribute to a carry-over effect from FES and increase the
      percentage of PwMS who benefit from this technology.

PMID- 28427701
TI  - Multiple sclerosis showing elevation of adenosine deaminase levels in the
      cerebrospinal fluid.
AB  - An 80-year-old man developed dysarthria, quadriplegia, sensory disturbance and
      ataxia in all limbs. Brain and spinal magnetic resonance imaging (MRI) revealed
      multiple enhanced lesions. Cerebrospinal fluid (CSF) levels of adenosine
      deaminase (ADA) remarkably elevated. Tuberculosis DNA was not detected, and
      tuberculosis was not cultured either in the CSF. Brain biopsy revealed the
      inflammatory demyelinating lesions. With the diagnosis of multiple sclerosis,
      corticosteroid therapy resulted in rapid improvement of his symptoms and MRI
      abnormalities. CSF levels of ADA also decreased. Multiple sclerosis should be
      included in differential diagnosis of disorders with ADA elevation in the CSF.

PMID- 28427702
TI  - Long-term clinical and radiologic follow-up of Schilder's disease.
AB  - BACKGROUND: Schilder's disease is a rare, subacute, or chronic demyelinating
      disorder that mainly affects children and generally shows a monophasic course.
      CASE: Here, we present three boys diagnosed with Schilder's disease, age at onset
      10-14 years, and followed up for 4-8 years. All of them presented with headache,
      two with encephalopathy and vomiting, and one with diplopia and vertigo. Cranial
      magnetic resonance imaging (MRI) showed two large demyelinating lesions,
      asymmetric in two patients and symmetric in the other. They were treated with
      steroid therapy. There were no radiologic relapses after discontinuation of
      corticosteroid therapy in all patients, but clinical attack without objective
      clinical findings was observed in one patient. Mild memory deficits and decline
      in school performance were the only neurologic sequelae in two patients. Cranial
      MRI findings showed significant shrinkage, but persistent T2-weighted
      hyperintensity of white matter lesions and loss of ring contrast enhancement at
      the end of the steroid therapy. There were no differences between the radiologic
      findings at the end of the steroid therapy and subsequent follow-ups. CONCLUSION:
      Although Schilder's disease is considered to be a variant of MS, it behaves more
      like ADEM with its monophasic course, and low recurrence rates. Radiologic
      features include shrinkage of mass lesions after steroid therapy, but sequel
      lesions remain same at the subacute and chronic stage.

PMID- 28427703
TI  - Multiple sclerosis among Afghan immigrants in Isfahan, Iran.
AB  - BACKGROUND: Multiple sclerosis is a central nervous system demyelinating disease
      with unknown etiology. However, it is believed to be a multifactorial disease
      resulting from an interaction of genetic and environmental factors. Immigrant
      studies have been performed to provide a better view of the pattern of this
      interaction. We aimed to report the prevalence of MS Afghan immigrants of
      Isfahan, a population who share the same environment as Isfahan residents but
      with different genetic backgrounds. PATIENTS AND METHODS: Medical documents of
      4536 patients registered by Isfahan Multiple Sclerosis Society (IMSS), the only
      MS registry in the province of Isfahan, were reviewed for Afghan patients and the
      demographic and clinical characteristics. The information on the current
      population of Afghans residing in the province was gathered through Bureau for
      Aliens and Foreign Immigrants Affairs (BAFIA). RESULTS: Six Afghan cases were
      identified among 4536 patients registered by IMSS. Current population of Afghans
      in the province was 123,578 people (65,041 male and 58,537 female). One of the
      cases was male and the other five were females with a female/male ratio of 5:1.
      Sex-adjusted prevalence for males and females was 1.53 and 8.54 per 100,000,
      respectively. The overall crude prevalence for Afghan population of Isfahan is
      4.85 per 100,000. CONCLUSION: This study shows a lower prevalence of MS among
      Afghan residents of Isfahan compared to the overall prevalence of the province.
      Our result could be implying a stronger bond between genetic factors and
      developing MS, rather than the environmental factors.

PMID- 28427704
TI  - Comparison of brain and spinal cord magnetic resonance imaging features in
      neuromyelitis optica spectrum disorders patients with or without aquaporin-4
      antibody.
AB  - BACKGROUND: The spinal cord and brain measurements are rarely investigated in
      neuromyelitis optica (NMO) patients with and without antibodies to aquaporin-4
      (AQP4), directly compared to multiple sclerosis (MS) patients. OBJECTIVES: To
      investigate magnetic resonance imaging (MRI) features of both brain and spinal
      cord in NMO patients with and without antibodies to AQP4, compared with MS
      patients and healthy controls (HC). METHODS: We recruited 55 NMO including 30
      AQP4 (+) and 25 AQP4 (-), 25 MS and 25 HC. Brain and spinal cord MRIs were
      obtained for each participant. Brain lesions (BL), whole brain and deep grey
      matter volumes (DGMV), white matter diffusion metrics and spinal cord lesions
      were measured and compared among groups. RESULTS: The incidence of BL was lower
      in the AQP4 (+) group than in the AQP4 (-) and MS groups (p<0.05). In the AQP4
      (+) group, there was a lower incidence of infratentorial lesions (ITL) and higher
      spinal cord lesions length than in the MS group (p<0.05). The thalamic and
      hippocampal volumes were smaller in the AQP4 (-) group and MS group than in the
      HC group (p<0.05). CONCLUSIONS: The NMO patients with AQP4 (-) showed higher
      prevalence of BL, ITL, and similar spinal cord lesion length, compared to AQP4
      (+), and demonstrated deep grey matter atrophy, suggesting an intermediate
      phenotype between that of typical MS and NMO.

PMID- 28427705
TI  - Presence of central veins and susceptibility weighted imaging for evaluating
      lesions in multiple sclerosis and leukoaraiosis.
AB  - PURPOSE: The process of demyelination in multiple sclerosis (MS) is reflected in
      lesions of the central nervous system (CNS), which are found in an abundance of
      different diseases and are frequently radiographically indistinguishable. Our aim
      was to determine whether the perivenous distribution of MS lesions identified on
      susceptibility weighted images (SWI) could be used as a specific radiographic
      sign for MS, and also to determine whether the visibility of the central vein
      (CV) is affected by the activity of MS lesions. METHODS: We retrospectively
      examined 34 subjects with MS and 19 subjects with ischemic lesions, which
      underwent a 3T MRI investigation. According to FLAIR and T2-weighted sequences
      the lesions were categorized regarding location. The presence of CVs was
      determined on SWI. Gadolinium enhanced T1-weighted sequence was included for the
      evaluation of MS lesion activity. RESULTS: A total load of 601 MS and 204
      ischemic lesions was identified. We found significantly more lesions with CVs in
      the group with ischemic lesions compared to the group with MS lesions (p<0.001).
      Similarly, significantly more supratentorial peripheral ischemic lesions had CVs
      (p=0.011), whereas in supratentorial periventricular and intratentorial lesions
      we found no significant difference between the two groups (p=0.377 and p=0.615).
      Comparing the active and inactive MS lesions regarding CVs, we found no
      significant difference between the groups (p=0,472). CONCLUSIONS: We can conclude
      that the presence of a CV is not a specific radiographic sign for MS. CVs can
      also be identified in lesions caused by various other diseases.

PMID- 28427707
TI  - Incidence of multiple sclerosis in the Republic of Ireland: A prospective
      population-based study.
AB  - BACKGROUND: Multiple sclerosis (MS) incidence and prevalence is increasing
      worldwide, with a disproportionally higher rate in women. Recent studies have
      questioned the presence of a latitudinal gradient in Europe. Ireland is a high
      prevalence country for MS with a previously reported North-South gradient making
      it ideal to further explore this concept. OBJECTIVES: In this study we
      prospectively determined the incidence rate of newly diagnosed MS in Ireland over
      a 12-month period and demonstrated the presence of a North-South gradient.
      METHODS: A national prospective population-based observational study was
      performed to ascertain all new cases of MS diagnosed from 1st March 2014 - 28th
      February 2015 in the Ireland. Within the main study there was a smaller nested
      cohort study to explore clinical outcomes with a view to future prospective
      follow-up of this cohort. Sources of case ascertainment included neurologists, MS
      nurse specialists and MS support services. The Irish census 2011 was used to
      obtain population statistics and the incidence rate was age-standardized to a
      European Standardised Population (ESP 2011). The North-South gradient was
      assessed, by comparing incidence rates between northern and southern counties.
      RESULTS: 292 patients fulfilled the inclusion criteria equating to an age
      standardised incidence rate (A-SIR) of 6/100,000 (95% CI: 5.3-6.6); for women the
      rate was 8.7/100,000 (95% CI: 7.7-9.6) and for men 3.3/100,000 (95% CI: 3.0-3.7).
      The female to male sex ratio was 2.7:1. Mean age at diagnosis amongst the RRMS
      group was 37 years (SD: 9.6) and 55 years (SD: 7.7) in the PPMS group; there were
      no gender differences associated with age of diagnosis. Onset was progressive in
      10% of cases. A significant difference was seen in incidence rates between the
      northern region (A-SIR: 9.6*105, CI: 6.9-12.3) and the southern region (A-SIR:
      5.1*105, CI: 3.8-6.3) (Z-score =3.34, p<0.05). Amongst the nested cohort (n=113)
      mean age at symptom onset in the RRMS group (n=106) was 34 years (SD: 8.7) and 50
      years (SD: 11.8) in the PPMS group (n=7). The female to male sex ratio was 3.5:1.
      Eighty percent had started or were due to start disease modifying therapy at time
      of review and 77% were taking supplemental vitamin D. Using the hospital
      depression and anxiety scale (HADS) mild to severe depressive symptoms were
      reported in 34% with no prior history of depression. Seventy-five percent were in
      full or part-time employment with 8% not working due to disability arising from
      their MS. CONCLUSIONS: This is the first study to prospectively assess the
      incidence rate of MS in Ireland and shows that Ireland has a high incidence rate,
      comparable with the rest of the British Isles, with a persistent North-South
      gradient. The age of onset of relapsing remitting multiple sclerosis appears to
      be increasing over the last 20 years. It will be of interest to re-assess this
      population over time to see if increasing incidence rates, as well as improved
      survival, are driving the reported increases in MS prevalence.

PMID- 28427706
TI  - Neuromyelitis optica spectrum disorder related tonic spasms responsive to
      lacosamide.
AB  - Paroxysmal tonic spasms [PTS] are common in patients with neuromyelitis optica
      spectrum disorder (NMOSD).1 2 In patients with demyelinating disease, PTS can
      significantly reduce the quality of life, limit activities of daily living and
      the rehabilitative process following an acute relapse 3. As in patients with
      multiple sclerosis (MS), paroxysmal tonic spasms in NMOSD usually respond well to
      treatment with carbamazepine.2 However, the optimal treatment in patients where
      carbamazepine is contraindicated or poorly tolerated is unclear. We describe a
      patient with NMOSD with severe paroxysmal tonic spasms who did not tolerate
      carbamazepine but was successfully treated with lacosamide (Vimpat).

PMID- 28427708
TI  - Increased incidence and prevalence of psoriasis in multiple sclerosis.
AB  - BACKGROUND: Psoriasis and multiple sclerosis (MS) share some risk factors, and
      fumarates are effective disease-modifying therapies for both psoriasis and MS,
      suggesting a common pathogenesis. However, findings regarding the occurrence of
      psoriasis in the MS population are inconsistent. OBJECTIVES: We aimed to estimate
      the incidence and prevalence of psoriasis in the MS population versus a matched
      cohort from the general population. METHODS: We used population-based
      administrative data from the Canadian province of Manitoba to identify 4911
      persons with MS and 23,274 age-, sex- and geographically-matched controls aged 20
      years and older. We developed case definitions for psoriasis using ICD-9/10 codes
      and prescription claims. These case definitions were compared to self-reported
      psoriasis diagnoses. The preferred definition was applied to estimate the
      incidence and prevalence of psoriasis over the period 1998-2008. We used
      multivariable Cox regression to estimate the risk of psoriasis in the MS
      population at the individual level, adjusting for sex, age at the index date,
      socioeconomic status and physician visits. RESULTS: In 2008, the crude incidence
      of psoriasis per 100,000 person-years was 466.7 (95%CI: 266.8-758.0) in the MS
      population, and 221.3 in the matched population (95%CI: 158.1-301.4). The crude
      prevalence of psoriasis per 100,000 persons was 4666.1 (95%CI: 3985.2-5429.9) in
      the MS population, and 3313.5 (95%CI: 3057.4-3585.3) in the matched population.
      The incidence and prevalence of psoriasis rose slightly over time. After
      adjusting for sex, age at the index date, socioeconomic status and physician
      visits, the risk of incident psoriasis was 54% higher in the MS population (HR
      1.54; 95%CI: 1.07-2.24). CONCLUSION: Psoriasis incidence and prevalence are
      higher in the MS population than in the matched population.

PMID- 28427709
TI  - Upper limb impairment is associated with use of assistive devices and
      unemployment in multiple sclerosis.
AB  - BACKGROUND: Individuals with multiple sclerosis (MS) frequently suffer from
      impaired sensory function, reduced strength and tremor in the upper limbs, which
      may interfere with upper limb function. However, upper limb impairment in MS is
      under-recognized and understudied. We aimed to evaluate the prevalence of upper
      limb impairment in a large sample of persons with MS; the association between
      upper limb function and employment status in MS; and the frequency of use of
      assistive devices aimed at addressing upper limb impairments. METHODS: We
      surveyed participants in the North American Research Committee on Multiple
      Sclerosis (NARCOMS) Registry regarding upper limb function using the ABILHAND
      questionnaire, and asked about use of assistive devices intended to improve the
      performance on upper limb activities. We evaluated the association between
      ABILHAND scores and current employment status using multivariable logistic
      regression analysis, and the association between ABILHAND scores and the use of
      an assistive device. RESULTS: Of 7463 eligible respondents, 5846 (78.3%) were
      female and mean (SD) age of 57.4 (10.2) years. The median (IQR) score on the
      ABILHAND was 45 (39-46). Higher levels of disability, as measured by the PDDS,
      correlated moderately with lower (worse) scores on the ABILHAND (r=-0.50; 95%CI: 
      0.48, -0.52). Over half of participants reported that they possessed an assistive
      device to aid upper limb function (3914, 56.0%). Older age, female sex, greater
      ambulatory disability, higher levels of fatigue, sensory impairment, spasticity
      and cognitive impairment, and visiting an occupational therapist were
      independently associated with increased odds of using an assistive device. After
      accounting for disability, perceived cognitive impairment, and fatigue, impaired
      upper limb function was associated with decreased odds of being employed (OR/1
      point rise in ABILHAND 0.97; 95%CI: 0.96, 0.98). CONCLUSIONS: Upper limb
      impairment is common in older MS patients, and adversely affects the ability to
      perform many common daily activities.

PMID- 28427710
TI  - Clinical outcomes and predictive factors related to good outcomes in plasma
      exchange in severe attack of NMOSD and long extensive transverse myelitis: Case
      series and review of the literature.
AB  - OBJECTIVE: To investigate the predictive factors associated with good outcomes of
      plasma exchange in severe attacks through neuromyelitis optica spectrum disorder
      (NMOSD) and long extensive transverse myelitis (LETM). In addition, to review the
      literature of predictive factors associated with the good outcomes of plasma
      exchange in central nervous system inflammatory demyelinating diseases (CNS
      IDDs). METHODS: Retrospective study in 27 episodes of severe acute attacks
      myelitis and optic neuritis in 24 patients, including 20 patients with NMOSD
      seropositive, 1 patient with NMOSD seronegative and 3 patients with LETM. Plasma
      exchange was performed, reflecting poor responses to high-dose intravenous
      methylprednisolone (IVMP) therapy. The outcomes of the present study were the
      functional outcome improvements at 6 months after plasma exchange. The predictive
      factors of good outcomes after plasma exchange were determined in this cohort,
      and additional factors reported in the literature were reviewed. RESULTS: Plasma
      exchange was performed in 16 spinal cord attacks and 11 attacks of optic
      neuritis. Twenty patients were female (83%). The median age of the patients at
      the time of plasma exchange was 41 years old. The median disease duration was 0.6
      years. The AQP4-IgG status was positive in 20 patients (83%). Plasma exchange
      following IVMP therapy led to a significant improvement in 81% of the cases after
      6 months of follow up. A baseline Expanded Disability Status Scale (EDSS) score
      <=6 before the attack was associated with significant improvement at 6 months
      (p=0.02, OR 58.33, 95%CI 1.92-1770). In addition, we reviewed the evidence for
      factors associated with good outcomes of plasma exchange in CNS IDDs, classified
      according to pre-plasma exchange, post-plasma exchange, and radiological
      features. CONCLUSION: Plasma exchange following IVMP therapy is effective as a
      treatment for patients experiencing a severe attack of NMOSD or LETM. The factors
      associated with good outcomes after plasma exchange in CNS IDDs are reviewed in
      the literature. We classified 3 different aspects, including pre-plasma exchange
      factors, based on minimal disability at baseline, preserved reflexes, early
      initiation, and short disease duration; post plasma exchange factors, including
      early improvement or lower disability at last follow up; and radiographic
      factors, for which the presence of active gadolinium lesions and the absence of
      spinal cord atrophy seem to be good outcomes for plasmapheresis.

PMID- 28427711
TI  - Maternal and perinatal characteristics of infants who, later in life, developed
      multiple sclerosis: Record-linkage study.
AB  - BACKGROUND: Pre-natal and early life factors may have a role in multiple
      sclerosis (MS) pathogenesis in some people. However, the reporting of any
      influence of maternal and perinatal factors on MS risk has been limited. We aimed
      to study maternal and perinatal characteristics of babies who went on to develop
      MS. METHODS: Data were analysed from the historical Oxford Record Linkage Study
      dataset 1970-1989, which incorporated a specialised maternity dataset with record
      linkage between mother and baby, covering a population of 850,000. Each maternal
      admission record, and records of her baby, were linked to any prior or subsequent
      recorded day-case or inpatient hospital admission episodes 1963-2011. The file of
      the offspring was searched for a subsequent record of MS, and the maternal and
      perinatal characteristics of the offspring with a record of MS were compared with
      those with no record of MS. RESULTS: There was a record of MS for 75 of the
      offspring, of whom 60 were female. MS was significantly more common in children
      of mothers who smoked (OR=2.1 (95%CI 1.0-4.7). There was a tendency towards an
      elevated risk of MS in children of mothers of lower social classes (social class
      4+5 OR=1.9 (0.9-3.9)). There were no significant associations between MS in the
      offspring and mothers' marital status, maternal weight, parity, pre-eclampsia,
      blood group, or babies' birth weight, birth weight for gestational age, mode of
      delivery, or presentation at delivery. CONCLUSIONS: This study does not support
      an important role for most studied maternal and perinatal factors in influencing
      MS risk. The possible exceptions, speculatively because numbers of subjects with
      MS were small, were maternal smoking, and pre-term birth. Future work, using
      datasets that would yield bigger numbers of cases of MS, should explore
      interactions between perinatal factors that are unlikely to be acting
      independently.

PMID- 28427712
TI  - Editors' Welcome.

PMID- 28427713
TI  - On the efficiency of instruction-based rule encoding.
AB  - Instructions have long been considered a highly efficient route to knowledge
      acquisition especially compared to trial-and-error learning. We aimed at
      substantiating this claim by identifying boundary conditions for such an
      efficiency gain, including the influence of active learning intention, repeated
      instructions, and working memory load and span. Our experimental design allowed
      us to not only assess how well the instructed stimulus-response (S-R) rules were
      implemented later on, but also to directly measure prior instruction encoding
      processes. This revealed that instruction encoding was boosted by an active
      learning intention which in turn entailed better subsequent rule implementation.
      As should be expected, instruction-based learning took fewer trials than trial
      and-error learning to reach a similar performance level. But more importantly,
      even when performance was measured relative to the identical number of preceding
      correct implementation trials, this efficiency gain persisted both in accuracy
      and in speed. This suggests that the naturally greater number of failed attempts
      in the initial phase of trial-and-error learning also negatively impacted
      learning in subsequent trials due to the persistence of erroneous memory traces
      established beforehand. A single instruction trial was sufficient to establish
      the advantage over trial-and-error learning but repeated instructions were
      better. Strategic factors and inter-individual differences in WM span - the
      latter exclusively affecting trial-and-error learning presumably due to the
      considerably more demanding working memory operations - could reduce or even
      abolish this advantage, but only in error rates. The same was not true for
      response time gains suggesting generally more efficient task automatization in
      instruction-based learning.

PMID- 28427714
TI  - [The GLITRAD (Adult Brainstem Gliomas) network: A national multidisciplinary
      group dedicated to brainstem gliomas in adults].

PMID- 28427715
TI  - Multiplexed Dynamic Imaging of Genomic Loci by Combined CRISPR Imaging and DNA
      Sequential FISH.
AB  - Visualization of chromosome dynamics allows the investigation of spatiotemporal
      chromatin organization and its role in gene regulation and other cellular
      processes. However, current approaches to label multiple genomic loci in live
      cells have a fundamental limitation in the number of loci that can be labeled and
      uniquely identified. Here we describe an approach we call "track first and
      identify later" for multiplexed visualization of chromosome dynamics by combining
      two techniques: CRISPR imaging and DNA sequential fluorescence in situ
      hybridization. Our approach first labels and tracks chromosomal loci in live
      cells with the CRISPR-Cas9 system, then barcodes those loci by DNA sequential
      fluorescence in situ hybridization in fixed cells and resolves their identities.
      We demonstrate our approach by tracking telomere dynamics, identifying 12 unique
      subtelomeric regions with variable detection efficiencies, and tracking back the
      telomere dynamics of respective chromosomes in mouse embryonic stem cells.

PMID- 28427716
TI  - Xenopus egg extract: A powerful tool to study genome maintenance mechanisms.
AB  - DNA repair pathways are crucial to maintain the integrity of our genome and
      prevent genetic diseases such as cancer. There are many different types of DNA
      damage and specific DNA repair mechanisms have evolved to deal with these
      lesions. In addition to these repair pathways there is an extensive signaling
      network that regulates processes important for repair, such as cell cycle control
      and transcription. Despite extensive research, DNA damage repair and signaling
      are not fully understood. In vitro systems such as the Xenopus egg extract
      system, have played, and still play, an important role in deciphering the
      molecular details of these processes. Xenopus laevis egg extracts contain all
      factors required to efficiently perform DNA repair outside a cell, using
      mechanisms conserved in humans. These extracts have been used to study several
      genome maintenance pathways, including mismatch repair, non-homologous end
      joining, ICL repair, DNA damage checkpoint activation, and replication fork
      stability. Here we describe how the Xenopus egg extract system, in combination
      with specifically designed DNA templates, contributed to our detailed
      understanding of these pathways.

PMID- 28427717
TI  - Factors affecting mortality in older trauma patients - A systematic review and
      meta-analysis.

PMID- 28427718
TI  - Improved linear quadratic and proportional control system for improved liquid
      level system regulation in a coke fractionation tower.
AB  - A new linear quadratic regulation (LQ) control plus a proportional (P) control
      system is proposed for the level regulation in an industrial coke fractionation
      tower. The process is first stabilized using a P controller and then a subsequent
      LQ controller is designed for the P control system. The P control system is
      modeled as a generalized first order plus dead time (FOPDT) process using step
      response test and the LQ-P controller is designed through a new state space
      structure. Performance in terms of regulatory and servo issues were investigated.
      Simulation results showed that the proposed method is more robust and improves
      performance than traditional model predictive control.

PMID- 28427719
TI  - Improved finite-control-set model predictive control for active front-end
      rectifiers with simplified computational approach and on-line parameter
      identification.
AB  - In this paper, an improved finite-control-set model predictive control method is
      proposed for active front-end rectifiers where the computational effort and
      parameter mismatch problems are taken into account simultaneously. Specifically,
      a desired voltage vector which only requires one exploration is directly selected
      by using a single cost function, and the process of selection of the desired
      voltage vector is optimized by using a sector distribution method. Meanwhile, a
      model reference adaptive system-based online parameter identification approach is
      presented to alleviate the parameter mismatch problem. The advantages of the
      proposed method summarized as follows: First, the proposed algorithm reduces the
      eight possible voltage vectors to one. The exhaustive exploration can be avoided
      while the control performance is not deteriorated. Second, the proposed
      controller can mitigate performance degradation caused by the model parameter
      mismatch. Simulation results under various parameters operating conditions are
      presented to demonstrate the efficacy of the proposed method.

PMID- 28427720
TI  - Income inequality in the United States and its potential effect on oral health.
AB  - BACKGROUND: The authors explored the relationship between income inequality and
      self-reported oral health and oral health-related quality of life. METHODS: The
      authors used an online survey to gather data about US adults' perceptions of
      their overall oral health and how oral health affected their quality of life. The
      authors categorized respondents as coming from areas of low, medium, or high
      income inequality on the basis of a county-level Gini coefficient. RESULTS:
      Results of chi2 tests and an analysis of variance indicated that there was a
      significant association between income inequality and oral health as measured by
      using the overall condition of the mouth and teeth, life satisfaction, and
      frequency of experiencing functional and social problems related to oral health.
      Generally, adults from areas of lower income inequality reported better oral
      health and oral health-related quality of life. CONCLUSIONS: Income inequality
      has the potential to affect both functional and social dimensions of oral health,
      possibly through a psychosocial pathway. Future research is necessary to
      determine whether any causal link exists. PRACTICAL IMPLICATIONS: Our findings
      may inform oral health policy. Long-term policies designed to improve the oral
      health of Americans could work best when supported by policies designed to reduce
      levels of income inequality, and thereby, may reduce oral health inequalities.
      Further research is needed to examine the effectiveness of such policies.

PMID- 28427721
TI  - Infants' use of movement synchrony to infer social affiliation in others.
AB  - Infants socially engage with others and observe others' social interactions from
      early in life. One characteristic found to be important for signaling and
      establishing affiliative social relationships is physical coordination and
      synchronization of movements. This study investigated whether synchrony in
      others' movements signals affiliation to 12- and 15-month-old infants. The
      infants were shown a scene in which two characters moved either synchronously or
      non-synchronously with a third character in the center. Next, the center
      character made an affiliation declaration and subsequently approached and cuddled
      one of the two characters. Using measures of gaze, we gauged infants' inferences
      about whom the center character would affiliate with before the cuddling took
      place. We found that 15-month-olds, but not 12-month-olds, inferred that the
      center character would affiliate with the previously synchronous character,
      suggesting that they can make inferences about others' affiliation based on
      movement synchrony. The findings are discussed in terms of their relevance to the
      infants' personal preferences and the potential importance of first-person
      experience in the development of social cognition.

PMID- 28427722
TI  - Biomechanical investigation of post-operative C5 palsy due to ossification of the
      posterior longitudinal ligament in different types of cervical spinal alignment.
AB  - Post-operative C5palsies are among the most common complications seen after
      cervical surgery for ossification of the posterior longitudinal ligament (OPLL).
      Although C5 palsy is a well-known complication of cervical spine surgery, its
      pathogenesis is poorly understood and depends on many other factors. In this
      study, a finite element model of the cervical spine and spinal cord-nerve roots
      complex structures was developed. The changes in stress in the cord and nerve
      roots, posterior shift of the spinal cord, and displacement and elongation of the
      nerve roots after laminectomy for cervical OPLL were analyzed for three different
      cervical sagittal alignments (lordosis, straight, and kyphosis). The results
      suggest that high stress concentrated on the nerve roots after laminectomy could
      be the main cause of C5 palsy because ossification of ligaments increases spinal
      cord shifting and root displacement. The type of sagittal alignment had no
      influence on changes in cord stress after laminectomy, although cases of kyphosis
      with a high degree of occupying ratio resulted in greater increases in nerve root
      stress after laminectomy. Therefore, kyphosis with a high OPLL occupying ratio
      could be a risk factor for poor surgical outcomes or post-operative complications
      and should be carefully considered for surgical treatment.

PMID- 28427723
TI  - Health related quality of life in renal transplantation: 2 years of longitudinal
      follow-up.
AB  - BACKGROUND AND OBJECTIVE: Health related quality of life (HRQoL) is recognized as
      an outcome measure in kidney transplantation. In this study was assessed changes
      on HRQoL and kidney-specific symptoms, also was evaluated the effect of socio
      demographic and clinical parameters on patient's perceived HRQoL. PATIENTS AND
      METHOD: A longitudinal study was done, at 5 time-points over 2 years after
      transplantation. To evaluate HRQoL the Kidney Disease Quality of Life
      Questionnaire Short Form was administrated, and Hospital Anxiety and Depression
      Scale was used to assess psychological distress. RESULTS: At 6-months after
      transplantation, patients had similar HRQoL scores compared to the general
      population. The improvement on effects of kidney disease domain could be
      considered as large (eta2=0.29), and medium on burden of kidney disease domain
      (eta2=0.12), work status domain (eta2=0.12), and sexual function domain
      (eta2=0.13). Psychological distress, depressive symptoms, haemoglobin, and serum
      creatinine had significant influence on patient's perceived HRQoL over 2 years
      after transplantation. CONCLUSIONS: An improvement of HRQoL was observed on
      general and specific-targeted symptoms over 2 years after renal transplantation.

PMID- 28427724
TI  - Disease-related malnutrition: A transversal improvement area.

PMID- 28427725
TI  - Association of Mild Leg Length Discrepancy and Degenerative Changes in the Hip
      Joint and Lumbar Spine.
AB  - OBJECTIVE: The purpose of this study was to evaluate the correlation between mild
      leg length discrepancy (LLD) and degenerative joint disease (DJD) or
      osteoarthritis. METHODS: We evaluated standard postural lumbopelvic radiographs
      from 255 adults (121 women and 134 men) who had presented with spinal pain for
      chiropractic care. Symmetry of femoral head diameters was used to exclude
      magnification errors. Pearson's partial correlation was used to control for age
      and derive effect sizes for LLD on DJD in the hip and lower lumbar motion
      segments. Krippendorff's alpha was used for intraobserver and interobserver
      reliability. RESULTS: A strong correlation was found between LLD and hip DJD in
      men (r = 0.532) and women (r = 0.246). We also found a strong correlation between
      LLD and DJD at the L5-S1 motion segment in men (r = 0.395) and women (r = 0.246).
      At the L4-5 spinal level this correlation was much attenuated in men (r = 0.229)
      and women (r = 0.166). CONCLUSIONS: These findings suggest an association between
      LLD and hip and lumbar DJD. Cause-effect relationships between mild LLD and DJD
      deserve to be properly evaluated in future longitudinal cohort studies.

PMID- 28427726
TI  - A 20-Year-Old Woman With Severe Opioid Toxicity.

PMID- 28427727
TI  - Implementation of Human Trafficking Education and Treatment Algorithm in the
      Emergency Department.
AB  - PROBLEM: Health care professionals have not been successful in recognizing or
      rescuing victims of human trafficking. The purpose of this project was to
      implement a screening system and treatment algorithm in the emergency department
      to improve the identification and rescue of victims of human trafficking. The
      lack of recognition by health care professionals is related to inadequate
      education and training tools and confusion with other forms of violence such as
      trauma and sexual assault. METHODS: A multidisciplinary team was formed to assess
      the evidence related to human trafficking and make recommendations for practice.
      After receiving education, staff completed a survey about knowledge gained from
      the training. An algorithm for identification and treatment of sex trafficking
      victims was implemented and included a 2-pronged identification approach: (1)
      medical red flags created by a risk-assessment tool embedded in the electronic
      health record and (2) a silent notification process. Outcome measures were the
      number of victims who were identified either by the medical red flags or by
      silent notification and were offered and accepted intervention. RESULTS: Survey
      results indicated that 75% of participants reported that the education improved
      their competence level. The results demonstrated that an education and treatment
      algorithm may be an effective strategy to improve recognition. One patient was
      identified as an actual victim of human trafficking; the remaining patients
      reported other forms of abuse. IMPLICATIONS FOR PRACTICE: Education and a
      treatment algorithm were effective strategies to improve recognition and rescue
      of human trafficking victims and increase identification of other forms of abuse.

PMID- 28427728
TI  - With a little help from my child: A dyad approach to immigrant mothers' and
      adolescents' socio-cultural adaptation.
AB  - Intergenerational adjustment theories suggest that immigrant adolescents may be
      particularly influential in their families, as they take on family obligations
      and serve as language brokers. Empirical research in this regard is, however,
      scarce. One aim of this study was to test whether adolescents' linguistic
      competence in German adds to the explanation of maternal socio-cultural
      adaptation difficulties in Germany. Another aim was to investigate whether the
      association between adolescents' linguistic competence and maternal socio
      cultural adaptation difficulties differs depending on adolescents' involvement in
      family obligations. The sample comprised 185 ethnic German immigrant mother
      adolescent dyads from the former Soviet Union (15.7 years old; 60% female).
      Results of Actor-Partner Interdependence Models, which were developed for dyad
      data analysis, indicated that mothers of adolescents with a good command of
      German indeed report fewer socio-cultural adaptation difficulties. The
      transmission effect from adolescent to mother was particularly pronounced when
      the adolescent was heavily involved in family obligations.

PMID- 28427729
TI  - Rickettsia conorii: Unusual cause of diarrhoea.

PMID- 28427730
TI  - Subvesical duct injury resolved by percutaneous drainage.

PMID- 28427731
TI  - Social identity and support for counteracting tobacco company marketing that
      targets vulnerable populations.
AB  - RATIONALE: Tobacco companies use advertising to target vulnerable populations,
      including youth, racial/ethnic minorities, and sexual minorities. OBJECTIVE: We
      sought to examine how personal identity affects support for population-specific
      anti-smoking advertisements that could serve as countermeasures to industry
      marketing practices. METHODS: In 2014-2015, we surveyed probability phone samples
      of adults and adolescents (n = 6,139) and an online convenience sample of adults
      (n = 4,137) in the United States. We experimentally varied the description of
      tobacco industry marketing practices (no description, general, or specific to a
      target group). The four prevention target groups were teens; African Americans;
      Latinos; and gays, lesbians, and bisexuals (GLBs). Participants were either
      members or non-members of their prevention target group. RESULTS: Support was
      highest for anti-smoking advertisements targeting teens, moderate for Latinos and
      African Americans, and lowest for GLBs. In-group members expressed higher support
      than out-group members when anti-smoking advertisements targeted African
      Americans, Latinos, and GLBs (all p < 0.05). However, when teens were the target
      prevention group, in-group members expressed lower support than out-group members
      (p < 0.05). The description of industry marketing practices did not have an
      effect. Results were similar across the phone and online studies. CONCLUSIONS:
      Our findings suggest that the public strongly supports advertisements to prevent
      smoking among teens, but support for similar efforts among other vulnerable
      populations is comparatively low. Anti-smoking campaigns for vulnerable
      populations may benefit from a greater understanding of the role of social
      identity in shaping public support for such campaigns.

PMID- 28427732
TI  - Endogenous bacterial endophthalmitis. A report of 2cases.
AB  - CLINICAL CASES: The cases are presented on 2patients with bacterial endogenous
      endophthalmitis. The first one was caused by Streptococcus bovis, developed after
      colonoscopy, which had a poor outcome and resulted in evisceration. The second
      case was caused by a methicillin resistant Staphylococcus aureus from an
      arthrodesis complicated with a para-spinal abscess. It had an excellent visual
      outcome. DISCUSSION: Bacterial endogenous endophthalmitis is a rare, but serious
      ocular disease that occurs when bacteria reach the eye via the bloodstream. It
      requires a very early diagnosis based on the clinical symptoms and patient
      history. A suitable and specific treatment with intravenous and intravitreal
      antibiotics may prevent a bad visual prognosis in some cases.

PMID- 28427733
TI  - Condyloma-like lesions in a young woman: Not always synonym of genital warts.

PMID- 28427734
TI  - Comparison of Outcomes and Prognosis of Patients With Versus Without Newly
      Diagnosed Diabetes Mellitus After Primary Percutaneous Coronary Intervention for
      ST-Elevation Myocardial Infarction (the HORIZONS-AMI Study).
AB  - A history of diabetes mellitus (DM) is an independent predictor for adverse
      events in patients with acute ST-segment elevation myocardial infarction (STEMI)
      undergoing primary percutaneous coronary intervention. Outcomes of patients with
      STEMI and newly diagnosed DM (NDM) are less well described. We used the
      Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial
      Infarction (HORIZONS-AMI) trial database to identify the outcomes at 30 days and
      3 years according to no, known, and NDM in patients with STEMI. In HORIZONS-AMI,
      3,602 patients with STEMI were randomized to bivalirudin versus heparin and a
      glycoprotein IIb/IIIa inhibitor, and eligible patients were randomized again to a
      paclitaxel-eluting stent or a bare-metal stent. DM was defined as a history of
      hyperglycemia managed by insulin, oral hypoglycemic agents, or diet. NDM was
      defined as the absence of previous diagnosis or treatment for DM at baseline and
      its addition at discharge. DM was present in 593/3,599 patients (16.5%), and NDM
      was diagnosed in 130 cases (3.6%). Compared with nondiabetics, those with DM and
      NDM had higher 3-year rates of death (11.4% and 12.0% vs 5.6%, respectively, p
      <0.0001) and major adverse cardiac events (29.6% and 30.2% vs 19.9%,
      respectively, p <0.0001). There were no significant differences in adverse events
      between new and known diabetic patients. DM and NDM were independent predictors
      of 3-year mortality and 3-year major adverse cardiac events. In conclusion,
      patients with NDM have a similarly poor prognosis after primary percutaneous
      coronary intervention in STEMI as those with previously established DM.

PMID- 28427735
TI  - Comparison of Frequency and Characteristics of Patients With Atrial Fibrillation
      Having Ablation With Versus Without Coronary Narrowing (>=50%) by Angiography.
AB  - Atrial fibrillation (AF) shares background comorbidities with coronary artery
      disease (CAD), including hypertension and diabetes mellitus. The aim of the study
      is to evaluate the prevalence, risk factors, and prognostic significance of CAD
      among patients who underwent catheter ablation for AF. In 544 consecutive
      registered patients who underwent catheter ablation for AF (CHADS2 score 1.2 +/-
      1.1, paroxysmal AF 57%), quantitative coronary angiography was used to detect
      CAD, defined as luminal narrowing of >=50% in diameter. Univariate and multiple
      logistic regression analyses were applied to evaluate the risk factors of CAD.
      Subsequent clinical events up to 1 year were obtained in all the patients. CAD
      was found in 70 patients (13%). The factors associated with the presence of CAD
      in AF patients who underwent catheter ablation were similar to traditional
      coronary risk factors such as hypertension and diabetes mellitus. AF patients
      with CAD had a higher CHADS2 score than those without CAD (1.5 +/- 1.1 vs 1.1 +/-
      1.0, p = 0.009). Hence, a CHADS2 score >=1 may be an alternative risk factor to
      predict CAD. Previous coronary revascularization (14% with CAD vs 6% without CAD)
      and paroxysmal AF (69% vs 55%) were also associated with CAD. During follow-up,
      patients with CAD experienced acute coronary syndrome (n = 2) and coronary
      revascularization (n = 18); no such events were recorded in those without CAD. In
      addition to traditional risk factors, CHADS2 score, previous revascularization,
      and paroxysmal AF may be new risk factors for CAD in AF patients.

PMID- 28427736
TI  - Interactions Between Reciprocal ST-Segment Downsloping During ST-Elevated
      Myocardial Infarction and Global Cardiac Perfusion and Functional Abnormalities.
AB  - Reciprocal ST-segment downsloping on electrocardiogram is a frequent finding
      during ST-elevated myocardial infarction (STEMI), but its etiology is still
      disputed. We sought to evaluate the relation between reciprocal ST-segment
      downsloping during STEMI and major cardiac perfusion and functional parameters.
      One hundred eighty-five patients with STEMI underwent emergency coronary
      angiography. The presence of reciprocal ST-segment downsloping was assessed. At
      coronary angiography, the corrected TIMI frame count (cTFC) was computed both on
      culprit and remote vessels and the occurrence of "no/slow reflow" phenomenon
      after percutaneous coronary intervention (PCI) identified. The left ventricular
      wall motion score index ratio (discharge/admission values) at echocardiography
      and the slope of high-sensitivity troponin elimination were computed as measures
      of effective myocardial reperfusion. Reciprocal ST-segment downsloping was
      revealed in 91 patients (49%). They presented higher cTFC values on remote
      vessels than patients without reciprocal electrocardiographic abnormalities (44
      +/- 18 vs 37 +/- 15 cineframes * second-1, p = 0.004). The presence of remote ST
      segment downsloping was also associated with a higher prevalence of "no/slow
      reflow" phenomenon (59% vs 40%, p = 0.013) as well as more abnormal values of
      wall motion score index ratio (p = 0.042) and high-sensitivity troponin slope (p
      = 0.012). At multivariate analyses, a higher cTFC on remote vessels predicted the
      occurrence of reciprocal ST-segment changes (p = 0.018) and the development of
      "no/slow reflow" phenomenon after PCI (p = 0.005). In conclusion, the presence of
      reciprocal ST-segment downsloping during STEMI clusters with significant
      perfusion and cardiac functional abnormalities, predicting the development of "no
      reflow" phenomenon after PCI.

PMID- 28427737
TI  - Common Hip Arthroplasty Problems-Useful Alternative Solutions From "Across the
      Pond".

PMID- 28427738
TI  - Assessment of a combined dry anaerobic digestion and post-composting treatment
      facility for source-separated organic household waste, using material and
      substance flow analysis and life cycle inventory.
AB  - The fate of total solids, volatile solids, total organic carbon, fossil carbon,
      biogenic carbon and 17 substances (As, Ca, CaCO3, Cd, Cl, Cr, Cu, H, Hg, K, Mg,
      N, Ni, O, P, Pb, S, Zn) in a combined dry anaerobic digestion and post-composting
      facility were assessed. Mass balances showed good results with low uncertainties
      for non-volatile substances, while balances for nitrogen, carbon, volatile solids
      and total organic carbon showed larger but reasonable uncertainties, due to
      volatilisation and emissions into the air. Material and substance flow analyses
      were performed in order to obtain transfer coefficients for a combined dry
      anaerobic digestion and post-composting facility. All metals passed through the
      facility and ended up in compost or residues, but all concentrations of metals in
      the compost complied with legislation. About 23% of the carbon content of the
      organic waste was transferred to the biogas, 24% to the compost, 13% to residues
      and 40% into the atmosphere. For nitrogen, 69% was transferred to the compost,
      10% volatilised to the biofilter, 11% directly into the atmosphere and 10% to
      residues. Finally, a full life cycle inventory was conducted for the combined dry
      anaerobic digestion and post-composting facility, including waste received, fuel
      consumption, energy use, gaseous emissions, products, energy production and
      chemical composition of the compost produced.

PMID- 28427739
TI  - Boosting biogas production from sewage sludge by adding small amount of agro
      industrial by-products and food waste residues.
AB  - In Greece, in many cities, wastewater treatment plants (WWTPs) operate their own
      anaerobic digestion (AD) facility in order to treat sewage sludge rather than
      achieve optimum biogas production. Nowadays, there is a growing interest
      regarding the addition of other co-substrates in these existing facilities in
      order to increase gas yield from the biomass. This practice may be possible by
      adding small amount of co-substrates which will not affect significantly in the
      designed hydraulic retention time. Nonetheless, the lack of experimental data
      regarding this option is a serious obstacle. In this study, the effect of co
      digestion sewage sludge, with small amount of agro-industrial by-products and
      food wastes is examined in lab-scale experiments. Specifically, co-digestion of
      SS and food waste (FW), grape residues (GR), crude glycerol (CG), cheese whey
      (CW) and sheep manure (SM), in a small ratio of 5-10% (v/v) was investigated. The
      effect of agro-industrial by-products and food waste residues on biogas
      production was investigated using one 1L and three 3L lab-scale reactors under
      mesophilic conditions at a 24-day hydraulic retention time. The biogas production
      rate reached 223, 259, 406, 572, 682 and 1751 mlbiogas/lreactor/d for 100% SS, 5%
      SM & 95% SS, 10% CW & 90% SS, 5% FW & 95% SS, 5% FW & 5% CG & 90% SS and 5% CG &
      95% SS respectively. Depending on the co-digestion material, the average removal
      of total chemical oxygen demand (TCOD) ranged between 20% (5% SM & 95% SS) and
      76% (5% FW & 5% CG & 90% SS). Reduction in the volatile solids ranged between 26%
      (5% SM & 95% SS) and 62% (5% FW & 5% CG & 90% SS) for organic loading rates
      between 0.8kgVSm-3d-1 and 2.0kgVSm-3d-1. Moreover, co-digestion improved biogas
      production from 14% (5% SM & 95% SS) to 674% (5% CG & 95% SS). This work suggests
      that WWTPs in Greece can increase biogas production by adding other wastes to the
      sewage sludge without affecting the operation of existing digesters and without
      requiring additional facilities.

PMID- 28427740
TI  - A Study of the Incidence and Management of Admissions for Cancer-related Symptoms
      in a District General Hospital: the Potential Role of an Acute Oncology Service.
AB  - AIMS: The non-specialist management of cancer patients is becoming increasingly
      complex. Acute oncology services (AOS), aiming to provide rapid access to
      specialist advice, have been shown to improve patient experience and reduce
      length of inpatient stay. The present study aimed to inform service provision in
      a district general hospital (DGH) by investigating cancer patients, not on active
      anti-cancer treatment, where the disease itself precipitated admission. This is a
      vulnerable group who are potentially disenfranchised of focused oncological input
      due to having less robust care pathways established to date. MATERIALS AND
      METHODS: A record was available of all cancer patients, not on active anti-cancer
      treatment, admitted to a Scottish DGH over a 3 month period. All but five of
      these patient records were retrospectively reviewed. RESULTS: The study group
      (n=63) comprised 31 males and 32 females; median age was 70 years (range 30-90).
      The most common reasons for admission were pain (33%), breathlessness (29%) and
      nausea/vomiting (27%). Symptoms/signs were experienced a median of 4.0 days
      (range 0.1-35.0) before admission. The median length of stay was 6 days (range 0
      39). Ten, 27 and 46% of patients were referred to a cancer nurse specialist,
      oncologist and palliative care team, respectively. Seventy-six per cent died
      within 6 months of admission. CONCLUSIONS: About one patient/day was admitted
      with cancer complications, many of whom will have contacted primary care in the
      week preceding admission. An AOS, integrating primary and secondary care, would
      benefit cancer patients by (i) optimising community care, potentially reducing
      hospital admissions and (ii) increasing inpatient specialist input to reduce
      length of inpatient stay. Implementation of an AOS would probably have a
      significant impact on both cancer patients at an individual level and service
      provision at a regional and national level.

PMID- 28427742
TI  - Investigating the biodiversity of ciliates in the 'Age of Integration'.
AB  - Biology is now turning toward a more integrative approach to research,
      distinguished by projects that depend on collaboration across hierarchical levels
      of organization or across disciplines. This trend is prompted by the need to
      solve complex, large-scale problems and includes disciplines that could be
      defined as integrative biodiversity. Integrative biodiversity of protists,
      including that of ciliates, is still partially in its infancy. This is the result
      of a shortage of historical data resources such as curated museum collections.
      Major areas of integrative biodiversity of ciliates that have begun to emerge can
      be categorized as integrative systematics, phenotypic plasticity, and integrative
      ecology. Integrative systematics of ciliates is characterized by inclusion of
      diverse sources of data in treatment of taxonomy of species and phylogenetic
      investigations. Integrative research in phenotypic plasticity combines
      investigation of functional roles of individual species of ciliates with genetic
      and genomic data. Finally, integrative ecology focuses on genetic identity of
      species in communities of ciliates and their collective functional roles in
      ecosystems. A review of current efforts toward integrative research into
      biodiversity of ciliates reveals a single, overarching concern-rapid progress
      will be achieved only by implementing a comprehensive strategy supported by one
      or more groups of active researchers.

PMID- 28427741
TI  - Management of biliary anastomotic strictures after liver transplantation.
AB  - Biliary strictures constitute 40% to 60% of the biliary complications after liver
      transplantation. They are more common after living donor related liver
      transplantation (LDLT) than orthotopic liver transplantation (OLT). Balloon
      dilation followed by multiple plastic stent insertion leads to a mean resolution
      rate of 84% in the treatment of ASs after OLT. Endoscopic treatment of ASs after
      LDLT is more difficult because of the small size of the ASs, their multiple
      number and peripheral location. Balloon dilation followed by multiple plastic
      stent insertion had a mean resolution rate of 53%. Percutaneous transhepatic
      biliary drainage was required in 16% to 44% of the patients. Refractory cases
      with complete biliary obstruction and severe stenosis, in whom the stricture
      could not be traversed with a guidewire, can be treated by magnetic compression
      anastomosis as a rescue therapy, if the anatomy of the bile ducts is suitable. In
      this review, we will focus on the endoscopic treatment of ASs, with special
      emphasis to refractory cases.

PMID- 28427743
TI  - Microbubble detection and ultrasound-guided vacuum-assisted biopsy of axillary
      lymph nodes in patients with breast cancer.
AB  - AIMS: To assess the feasibility of undertaking microbubble-guided vacuum-assisted
      biopsy (VAB) of the sentinel lymph node (SLN) and determine its sensitivity in
      detecting metastases. Patient experience and the impact of VAB on subsequent
      axillary surgery were also evaluated. MATERIALS AND METHODS: Patients with a
      normal axillary ultrasound or benign core biopsy planned for surgical SLN biopsy
      were recruited. Part 1 of the study was used to establish the technique of
      ultrasound microbubble contrast to detect the SLN. In Part 2 microbubble
      detection of the SLN was followed by 13 G VAB. All patients subsequently had
      surgical histological correlation. RESULTS: One hundred and thirty-nine patients
      were recruited: 36 to Part 1 and 103 to Part 2. Of the 100 patients in Part 2
      included for analysis, 82 (82%) underwent successful biopsy. Sensitivity for
      detecting metastases was 58.8% (95% confidence interval: 32.9%, 81.6%). The
      procedure was generally well tolerated; however, VAB interfered adversely with
      subsequent surgical SLN biopsy with surgeons reporting moderate or severe
      interference in 48% of patients and an additional 8.3% with complete failure of
      SLNB. CONCLUSION: It is possible to perform VAB of microbubble-detected SLNs.
      Although the sensitivity for detecting metastases was reasonable, the adverse
      effect on subsequent surgery was significant.

PMID- 28427744
TI  - Lung sounds research expands the horizon on chest auscultation.

PMID- 28427745
TI  - How to approach the acute respiratory distress syndrome: Prevention, plan, and
      prudence.
AB  - The acute respiratory distress syndrome (ARDS) is typically manifested by
      refractory hypoxemia with high mortality. A correct diagnosis is the first step
      to achieve better outcomes. An early intervention to manage modifiable risk
      factors of ARDS development and the avoidance of aggravating factors that
      increase disease severity and progression should be carefully addressed. A
      management plan is necessary at an early stage of ARDS to determine the level of
      intensive care. It should be carefully decided which therapeutic measures should
      be performed depending on the patient's underlying clinical condition. The
      clinician's considerate prudence is required in decisions of when to apply
      intensive measures for an ARDS treatment. Mechanical ventilator support should be
      carefully used depending on the patient's severity and pathological phase.
      Decreasing inappropriate alveolar strain through a low tidal volume under optimal
      positive end-expiratory pressure is key for ventilator support in ARDS. The
      extracorporeal membrane oxygenation applied in the experienced centers seems to
      improve the survival of patients with severe ARDS. A constellation of physical
      and psychological problems can develop or persist for up to 5 years in patients
      with ARDS. Therefore, an early mobilization with rehabilitation, even during an
      intensive care unit stay, should be seriously considered whenever feasible.
      Lastly, prevention of aspiration, stress ulcers, deep vein thrombosis, catheter
      related infection, overhydration, and heavy sedation is essential to achieve
      better outcomes in ARDS.

PMID- 28427746
TI  - Appendectomy, tonsillectomy, and risk for sarcoidosis - A hospital-based case
      control study in Japan.
AB  - BACKGROUND: The role of surgery in the onset of sarcoidosis is unclear. We
      investigated whether surgery is an internal environmental factor for sarcoidosis
      onset within the Japanese population. METHODS: We enrolled 222 patients diagnosed
      with sarcoidosis (78 men, 144 women) who were admitted to our department between
      1984 and 2012. We also enrolled 529 control subjects (251 men, 278 women), who
      were matched for sex, age at admission, and year of admission. Surgical history,
      family history, and smoking status were evaluated. RESULTS: Multivariate analysis
      correlated history of appendectomy (OR, 1.55; 95% CI, 1.05-2.29) and
      tonsillectomy (OR, 2.79; 95% CI, 0.91-8.56) with the occurrence of sarcoidosis;
      other surgical procedures had no correlation. In women, appendectomy had a
      stronger association with sarcoidosis (OR, 1.69; 95% CI, 1.05-2.73), as opposed
      to that in men (OR, 1.39; 95% CI, 0.68-2.85). This association was greater in
      women aged >=45 years than in those aged <45 years. There was a stronger
      correlation between tonsillectomy and sarcoidosis in women (OR, 3.30; 95% CI,
      0.88-12.39), than in men (OR, 1.26; 95% CI, 0.10-16.52). ORs for sarcoidosis were
      5.55 (95% CI, 2.02-15.27) and 0.97 (95% CI, 0.52-1.84) in women aged >=45 years
      with a history of appendectomy at <20 years and >=20 years, respectively, with
      the former being statistically significant. CONCLUSIONS: Appendix and tonsil
      removal was associated with sarcoidosis onset, suggesting their potential
      protective role against sarcoidosis development. Further studies are needed to
      minimize possible confounding factors.

PMID- 28427747
TI  - Percutaneous endoscopic gastrostomy for aspiration pneumonia: A 10-year single
      center experience.
AB  - BACKGROUND: The significance of percutaneous endoscopic gastrostomy (PEG) in
      patients with aspiration pneumonia is unknown. The purpose of this study was to
      evaluate the clinical characteristics and outcomes of aspiration pneumonia
      patients who underwent PEG. METHODS: A retrospective cohort study of consecutive
      patients hospitalized with pneumonia who underwent PEG from 2005 to 2014.
      RESULTS: Of 2281 cases of pneumonia, 92 patients with aspiration pneumonia
      underwent PEG during their hospital stay. The rate of PEG insertion significantly
      decreased after 2011, when Japanese therapeutic guidelines for pneumonia in the
      elderly were published (5.9% vs. 1.6% before and after guideline publication,
      respectively; p<0.01). The study population was male dominant (63%), with a mean
      age of 80.7 years. They had several risk factors for aspiration pneumonia, such
      as dementia (63.0%), cerebrovascular disorders (37.0%), and neurologic diseases
      (28.3%). Survival after PEG was 88.0% at day 30, 84.3% at 3 months, 73.8% at 6
      months, and 61.1% at 1 year with a median survival of 751 days. Pneumonia was the
      most common cause of death during the follow-up period (22 of 51 patients,
      43.1%). Cox proportional hazard model showed that independent predictors of
      mortality were older age, male gender, comorbidity of heart failure, and lower
      serum albumin values before PEG. CONCLUSIONS: The rate of PEG placement is
      decreasing after the Japanese guidelines were published in 2011. While the
      overall median survival was approximately 2 years, the most common cause of death
      was pneumonia and mortality was associated with some significant factors.

PMID- 28427748
TI  - Post-bronchoscopy pneumonia in patients suffering from lung cancer: Development
      and validation of a risk prediction score.
AB  - BACKGROUND: The incidence, risk factors, and consequences of pneumonia after
      flexible bronchoscopy in patients with lung cancer have not been studied in
      detail. METHODS: We retrospectively analyzed the data from 237 patients with lung
      cancer who underwent diagnostic bronchoscopy between April 2012 and July 2013
      (derivation sample) and 241 patients diagnosed between August 2013 and July 2014
      (validation sample) in a tertiary referral hospital in Japan. A score predictive
      of post-bronchoscopy pneumonia was developed in the derivation sample and tested
      in the validation sample. RESULTS: Pneumonia developed after bronchoscopy in 6.3%
      and 4.1% of patients in the derivation and validation samples, respectively.
      Patients who developed post-bronchoscopy pneumonia needed to change or cancel
      their planned cancer therapy more frequently than those without pneumonia (56%
      vs. 6%, p<0.001). Age >=70 years, current smoking, and central location of the
      tumor were independent predictors of pneumonia, which we added to develop our
      predictive score. The incidence of pneumonia associated with scores=0, 1, and >=2
      was 0, 3.7, and 13.4% respectively in the derivation sample (p=0.003), and 0,
      2.9, and 9.7% respectively in the validation sample (p=0.016). CONCLUSIONS: The
      incidence of post-bronchoscopy pneumonia in patients with lung cancer was not
      rare and associated with adverse effects on the clinical course. A simple 3-point
      predictive score identified patients with lung cancer at high risk of post
      bronchoscopy pneumonia prior to the procedure.

PMID- 28427749
TI  - A clinical method for detecting bronchial reversibility using a breath sound
      spectrum analysis in infants.
AB  - BACKGROUND: Using a breath sound analyzer, we investigated clinical parameters
      for detecting bronchial reversibility in infants. METHODS: A total of 59 infants
      (4-39 months, mean age 7.8 months) were included. In Study 1, the intra- and
      inter-observer variability was measured in 23 of 59 infants. Breath sound
      parameters, the frequency at 99% of the maximum frequency (F99), frequency at
      25%, 50%, and 75% of the power spectrum (Q25, Q50, and Q75), and highest
      frequency of inspiratory breath sounds (HFI), and parameters obtained using the
      ratio of parameters, i.e. spectrum curve indices, the ratio of the third and
      fourth area to total area (A3/AT and B4/AT, respectively) and ratio of power and
      frequency at F75 and F50 (RPF75 and RPF50), were calculated. In Study 2, the
      relationship between parameters of breath sounds and age and stature were
      studied. In Study 3, breath sounds were studied before and after beta2 agonist
      inhalation. RESULTS: In Study 1, the data showed statistical intra- and inter
      observer reliability in A3/AT (p=0.042 and 0.034, respectively) and RPF50
      (p=0.001 and 0.001, respectively). In Study 2, there were no significant
      relationships between age, height, weight, and BMI. In Study 3, A3/AT and RPF50
      significantly changed after beta2 agonist inhalation (p=0.001 and p<0.001,
      respectively). CONCLUSIONS: Breath sound analysis can be performed in infants, as
      in older children, and the spectrum curve indices are not significantly affected
      by age-related factors. These sound parameters may play a role in the assessment
      of bronchial reversibility in infants.

PMID- 28427750
TI  - Consensus statements for medical practice: Biological agents and lung disease
      [Abridged English translation by the Japanese Respiratory Society].

PMID- 28427751
TI  - Corrigendum to "A retrospective cohort study of outcome in systemic sclerosis
      associated interstitial lung disease" [Respir. Investig. 54 (2016) 445-453].

PMID- 28427752
TI  - Spontaneously Arising Tumours and Tumour-like Lesions of the Cervix and Uterus in
      83 Pet Guinea Pigs (Cavia porcellus).
AB  - Tumours and tumour-like lesions are rare findings in the genital system of guinea
      pigs. The aim of the present study was to characterize nodular lesions in the
      cervix and uterus of guinea pigs submitted for histopathological diagnosis.
      Samples from 83 pet animals were investigated. Cases included 64 surgically
      excised masses including complete uteri (n = 37), parts from uteri containing
      masses (n = 8), complete masses (n = 12) or samples from masses (n = 7) and 19
      complete necropsy examinations. In 55 of the cases, only solitary changes were
      observed; in 28 cases two or more lesions were diagnosed. Histopathological
      diagnoses included polyps in the vagina, cervix or uterus (n = 8), hyperplastic
      lesions of the endocervix (n = 10) and seven adenomas and two adenocarcinomas of
      the endocervix. Endometrial alterations included single small glandular cysts (n
      = 3), nodular glandular-cystic hyperplasia (n = 8), adenoma (n = 20) and
      adenocarcinoma (n = 3). Four placentas, 10 focal decidualizations and six
      deciduomas were found. Furthermore, 18 leiomyomas and nine leiomyosarcomas were
      diagnosed. Uterine malignant mixed Mullerian tumours were observed in seven
      cases. Overall, benign lesions outnumbered malignant tumours in the female
      genital tract of pet guinea pigs. Therefore, surgical excision or
      ovariohysterectomy should be recommended as therapy.

PMID- 28427754
TI  - Millennsials to the rescue?

PMID- 28427753
TI  - Prognostic markers in oropharyngeal squamous cell carcinoma: focus on CD70 and
      tumour infiltrating lymphocytes.
AB  - We evaluated the expression of CD70 as biomarker for prognosis in patients with
      oropharyngeal squamous cell carcinoma (OSCC). We also examined the prognostic
      value of tumour infiltrating lymphocytes (TILs) in our study cohort. Formalin
      fixed, paraffin embedded tissue originating from the oropharynx of 78 patients
      was immunohistochemically stained for CD70, CD3, CD8 and FoxP3. Expression of
      CD70, CD3, CD8, FoxP3 and HPV status was correlated with clinicopathological
      characteristics. Overall survival (OS) was determined by a log-rank (Mantel-Cox)
      test whereas the Cox proportional hazard model was used for multivariate
      analysis. CD70 expression demonstrated no influence on OS. Tumours heavily
      infiltrated by TILs were linked with better outcome, for the total number of TILs
      as well as for the CD3+ and CD8+ T cell count. A Cox proportional hazard model
      proved that solely CD8+ infiltrating T cells exhibit a positive effect on OS
      (HR=0.30, 95% confidence interval 0.13-0.72). Our results demonstrate that CD8+
      TILs constitute an independent prognosticator in patients diagnosed with OSCC.
      Further validation of the prognostic value of CD8+ TILs in OSCC is warranted and
      could provide us with a better insight into the immunological status of these
      malignancies.

PMID- 28427755
TI  - Do Maternity Care Coordination Services Encourage Use of Behavioral Health
      Treatment among Pregnant Women on Medicaid?
AB  - OBJECTIVE: Maternity care coordination (MCC) may provide an opportunity to
      enhance access to behavioral health treatment services. However, this
      relationship has not been examined extensively in the empirical literature. This
      study examines the effect of MCC on use of behavioral health services among
      perinatal women. METHODS: Medicaid claims data from October 2008 to September
      2010 were analyzed using linear fixed effects models to investigate the effects
      of receipt of MCC services on mental health and substance use-related service use
      among Medicaid-eligible pregnant and postpartum women in North Carolina (n =
      7,406). RESULTS: Receipt of MCC is associated with a 20% relative increase in the
      contemporaneous use of any mental health treatment (within-person change in
      probability of any mental health visit 0.5% [95% CI, 0.1%-1.0%], or an increase
      from 8.3% to 8.8%); MCC in the prior month is associated with a 34% relative
      increase in the number of mental health visits among women who receive MCC
      (within-person change in the number of visits received 1.7% [95 CI, 0.2%-3.3%],
      or from 0.44 to 0.46 mental health visits). No relationship was observed between
      MCC and Medicaid-funded substance use-related treatment services. CONCLUSIONS:
      MCC may be an effective way to quickly address perinatal mental health needs and
      engage low-income women in mental health care. However, currently there may be a
      lost opportunity within MCC to increase access to substance use-related
      treatment. Future studies should examine how MCC improves access to mental health
      care such that the program's ability can be strengthened to identify women with
      substance use-related disorders and transition them into available care.

PMID- 28427756
TI  - Human tissue Kallikreins: Blood levels and response to radiotherapy in
      intermediate risk prostate cancer.
AB  - OBJECTIVES: Kallikreins are serine proteases over expressed in many malignancies.
      In this study, we measure changes in serum kallikrein (KLKs) levels during
      intensity-modulated radiotherapy (IMRT) in prostate cancer patients, and find
      potential correlations between serum kallikrein level and normal tissues toxicity
      during radiation. METHODS: Forty-nine patients with prostate cancer were
      recruited as follows: group 1, definitive standard fractionation IMRT (78Gy in 39
      fractions, n=15); group 2, definitive hypofractionated IMRT (60Gy in 20
      fractions, n=15); and group 3, IMRT postprostatectomy (66Gy in 33 fractions,
      n=19). Patients treated with definitive radiation therapy were intermediate risk.
      Blood samples were collected at baseline and quarterly during IMRT and at each
      follow-up visit. Acute toxicity was graded weekly during radiotherapy using CTC
      AE v4.0 criteria. Multiplexed immunoassays were used to quantify total, free, and
      intact Prostate Specific Antigen (PSA), as well as Kallikreins 2, 4, 6, and 11.
      RESULTS: The serum kallikreins, PSA (total, free and intact), KLK2, 6, and 11
      change significantly after definitive radiotherapy. KLK2 and intact PSA decrease
      as fast as two weeks after initiation of radiation, while the first significant
      decrease in total and free PSA is noted only at the completion of radiation. KLK6
      and KLK11 surge temporarily during radiation therapy and decrease below baseline
      levels at 8weeks and 12months, respectively after completion of radiation. KLK4
      levels did not change with radiation. There was no correlation between GU or GI
      toxicities and serum kallikreins. CONCLUSIONS: PSA, KLK2, 6, and 11, change
      significantly after definitive prostate radiotherapy, though KLK2 and PSA
      decrease by the end of the radiation course while KLK6 and KLK11 decrease
      significantly starting at 2 and 12months, respectively, after radiation. There
      was no correlation between GU or GI toxicities and serum kallikreins.

PMID- 28427757
TI  - Involved-field irradiation concurrently combined with nedaplatin/5-fluorouracil
      for inoperable esophageal cancer on basis of 18FDG-PET scans: A long follow-up
      results of phase II study.

PMID- 28427758
TI  - [Dural venous sinuses thrombosis; an unexpected diagnosis].

PMID- 28427759
TI  - Polymorphisms in CYP2C8 and CYP3A5 genes in the Nigerian population.
AB  - Polymorphisms in CYP2C8 and CYP3A5 genes have implications for responses elicited
      by the ingestion of some xenobiotics, the metabolism of which are mediated by
      these enzymes. CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A5*6 and CYP3A5*7 are a few
      functionally-relevant variants of these genes which this study provides data for,
      in the Nigerian population. Blood samples were processed for genomic DNA from 178
      unrelated subjects spread across Nigerian ethnicities and screened for these
      polymorphism through the Sequenom iPLEX MassARRAY platform. Results obtained were
      further validated with Sanger sequencing of a few samples and thereafter, the
      genotype data were statistically processed. All alleles were in Hardy-Weinberg
      equilibrium and CYP2C8*2 occurred at a frequency (95% CI) of 0.194 (0.154,
      0.239), while CYP3A5*3, CYP3A5*6 and CYP3A5*7 were found at frequencies (95% CI)
      of 0.160 (0.124, 0.202), 0.096 (0.067, 0.131) and 0.126 (0.094, 0.166),
      respectively. However, CYP2C8*3 was not detected in the population. The study
      observed a 60% prevalence of carriers of at least a CYP3A5 polymorphism in the
      population, suggesting the probable existence of huge variability in CYP3A5
      activity which may prove significant in the administration of drugs with narrow
      therapeutic windows and whose metabolism is largely mediated by CYP3A5.

PMID- 28427760
TI  - Lateral lymph node recurrence after total thyroidectomy and central neck
      dissection in patients with papillary thyroid cancer without clinical evidence of
      lateral neck metastasis: Comment on data sparsity.

PMID- 28427761
TI  - Multidisciplinary management of head and neck cancer: First expert consensus
      using Delphi methodology from the Spanish Society for Head and Neck Cancer (part
      1).
AB  - Head and neck cancer is one of the most frequent malignances worldwide. Despite
      the site-specific multimodality therapy, up to half of the patients will develop
      recurrence. Treatment selection based on a multidisciplinary tumor board
      represents the cornerstone of head and neck cancer, as it is essential for
      achieving the best results, not only in terms of outcome, but also in terms of
      organ-function preservation and quality of life. Evidence-based international and
      national clinical practice guidelines for head and neck cancer not always provide
      answers in terms of decision-making that specialists must deal with in their
      daily practice. This is the first Expert Consensus on the Multidisciplinary
      Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the
      Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It
      offers several specific recommendations based on the available evidence and the
      expertise of our specialists to facilitate decision-making of all health-care
      specialists involved.

PMID- 28427762
TI  - Multidisciplinary management of head and neck cancer: First expert consensus
      using Delphi methodology from the Spanish Society for Head and Neck Cancer (part
      2).
AB  - Head and neck cancer is one of the most frequent malignances worldwide. Despite
      the site-specific multimodality therapy, up to half of the patients will develop
      recurrence. Treatment selection based on a multidisciplinary tumor board
      represents the cornerstone of head and neck cancer, as it is essential for
      achieving the best results, not only in terms of outcome, but also in terms of
      organ-function preservation and quality of life. Evidence-based international and
      national clinical practice guidelines for head and neck cancer not always provide
      answers in terms of decision-making that specialists have to deal with in their
      daily practice. This is the first Expert Consensus on the Multidisciplinary
      Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the
      Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It
      offers a number of specific recommendations based on the available evidence and
      the expertise of our specialists to facilitate decision-making of all health-care
      specialists involved.

PMID- 28427763
TI  - Exploring patient experiences and perspectives of a heart failure
      telerehabilitation program: A mixed methods approach.
AB  - OBJECTIVES: To describe patient experiences and perspectives of a group-based
      heart failure (HF) telerehabilitation program delivered to the homes via online
      video-conferencing. BACKGROUND: Limited information currently exists on patient
      experiences of telerehabilitation for HF. Patient feedback and end-user
      perspectives provide important information regarding the acceptability of this
      new delivery model which may have a substantial impact on future uptake. METHODS:
      We used mixed-methods design with purposive sampling of patients with HF. We used
      self-report surveys and semi-structured interviews to measure patient experiences
      and perspectives following a 12-week telerehabilitation program. The
      telerehabilitation program encompassed group-based exercise and education, and
      were delivered in real-time via videoconferencing. Interviews were transcribed
      and coded, with thematic analysis undertaken. RESULTS: Seventeen participants
      with HF (mean age [SD] of 69 [12] years and 88% males) were recruited.
      Participants reported high visual clarity and ease of use for the monitoring
      equipment. Major themes included motivating and inhibiting influences related to
      telerehabilitation and improvement suggestions. Participants liked the health
      benefits, access to care and social support. Participants highlighted a need for
      improved audio clarity and connectivity as well computer training for those with
      limited computer experience. The majority of participants preferred a combined
      face-to-face and online delivery model. CONCLUSION: Participants in this study
      reported high visual clarity and ease-of-use, but provided suggestions for
      further improvements in group-based video telerehabilitation for HF.

PMID- 28427764
TI  - Role of endoscopy in primary sclerosing cholangitis: European Society of
      Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the
      Liver (EASL) Clinical Guideline.
AB  - This guideline is an official statement of the European Society of
      Gastrointestinal Endoscopy (ESGE) and of the European Association for the Study
      of the Liver (EASL) on the role of endoscopy in primary sclerosing cholangitis.
      The Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      system was adopted to define the strength of recommendations and the quality of
      evidence. Main recommendations.

PMID- 28427765
TI  - EASL Clinical Practice Guidelines: The diagnosis and management of patients with
      primary biliary cholangitis.
AB  - Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune
      cholestatic liver disease, which when untreated will culminate in end-stage
      biliary cirrhosis. Diagnosis is usually based on the presence of serum liver
      tests indicative of a cholestatic hepatitis in association with circulating
      antimitochondrial antibodies. Patient presentation and course can be diverse and
      risk stratification is important to ensure all patients receive a personalised
      approach to their care. The goals of treatment and management are the prevention
      of end-stage liver disease, and the amelioration of associated symptoms.
      Pharmacologic approaches in practice, to reduce the impact of the progressive
      nature of disease, currently include licensed therapies (ursodeoxycholic acid and
      obeticholic acid) and off-label therapies (fibric acid derivatives, budesonide).
      These clinical practice guidelines summarise the evidence for the importance of a
      structured, life-long and individualised, approach to the care of patients with
      PBC, providing a framework to help clinicians diagnose and effectively manage
      patients.

PMID- 28427766
TI  - Evaluation of a Model of Integrated Care for Patients With Chronic Medical and
      Psychiatric Illness.
AB  - BACKGROUND: Chronic illnesses are prevalent in general medical and psychiatric
      practices, causing significant disease burden to care givers and providers.
      Systems of care that treat individuals with mental illness are often separate
      from general medical systems of care. OBJECTIVE: This study sought to compare the
      quality of life, satisfaction with care, and utilization of care in patients with
      comorbid chronic medical and mental illnesses. METHODS: A total of 64
      participants from an integrated medicine and psychiatry clinic (med/psych), were
      compared with 52 patients from separate internal medicine and psychiatry clinics
      (within the same institution) for quality of life, satisfaction with care, and
      utilization of care. RESULT: Patients receiving integrated care reported being
      more satisfied with care compared with patients treated separately. There were no
      differences in quality of life between the groups. A nonsignificant trend toward
      fewer emergency room visits and fewer hospital stays for the integrated care
      group compared with the separate care group was observed. CONCLUSION: This study
      demonstrated that integrated care for psychiatric and medical disorders improved
      the patients' experience of care and therefore may have positively affected the
      outcome of care. Further work is needed to compare medical and psychiatric
      comorbidities and costs of care and quality measures in these 2 groups.

PMID- 28427767
TI  - beta-arrestins negatively control human adrenomedullin type 1-receptor
      internalization.
AB  - Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful
      variety of protective effects against multiorgan damage through the AM type 1
      receptor (AM1 receptor), which consists of the calcitonin receptor-like receptor
      (CLR) and receptor activity-modifying protein 2 (RAMP2). Two beta-arrestin (beta
      arr) isoforms, beta-arr-1 and beta-arr-2, play a central role in the agonist
      induced internalization of many receptors for receptor resensitization. Notably,
      beta-arr-biased agonists are now being tested in phase II clinical trials,
      targeting acute pain and acute heart failure. Here, we examined the effects of
      beta-arr-1 and beta-arr-2 on human AM1 receptor internalization. We constructed a
      V5-tagged chimera in which the cytoplasmic C-terminal tail (C-tail) of CLR was
      replaced with that of the beta2-adrenergic receptor (beta2-AR), and it was
      transiently transfected into HEK-293 cells that stably expressed RAMP2. The cell
      surface expression and internalization of the wild-type or chimeric receptor were
      quantified by flow cytometric analysis. The [125I]AM binding and the AM-induced
      cAMP production of these receptors were also determined. Surprisingly, the
      coexpression of beta-arr-1 or -2 resulted in significant decreases in AM1
      receptor internalization without affecting AM binding and signaling prior to
      receptor internalization. Dominant-negative (DN) beta-arr-1 or -2 also
      significantly decreased AM-induced AM1 receptor internalization. In contrast, the
      AM-induced internalization of the chimeric AM1 receptor was markedly augmented by
      the cotransfection of beta-arr-1 or -2 and significantly reduced by the
      coexpression of DN-beta-arr-1 or -2. These results were consistent with those
      seen for beta2-AR. Thus, both beta-arrs negatively control AM1 receptor
      internalization, which depends on the C-tail of CLR.

PMID- 28427768
TI  - Syndrome of transient headache and neurological deficits with cerebrospinal fluid
      lymphocytosis (HaNDL) in a patient with confusional symptoms, diffuse EEG
      abnormalities, and bilateral vasospasm in transcranial Doppler ultrasound: A case
      report and literature review.
AB  - INTRODUCTION: HaNDL syndrome (transient headache and neurological deficits with
      cerebrospinal fluid lymphocytosis) is characterised by one or more episodes of
      headache and transient neurological deficits associated with cerebrospinal fluid
      lymphocytosis. To date, few cases of HaNDL manifesting with confusional symptoms
      have been described. Likewise, very few patients with HaNDL and confusional
      symptoms have been evaluated with transcranial Doppler ultrasound (TCD). TCD data
      from patients with focal involvement reveal changes consistent with vasomotor
      alterations. DEVELOPMENT: We present the case of a 42-year-old man who
      experienced headache and confusional symptoms and displayed pleocytosis, diffuse
      slow activity on EEG, increased blood flow velocity in both middle cerebral
      arteries on TCD, and single-photon emission computed tomography (SPECT) findings
      suggestive of diffuse involvement, especially in the left hemisphere.
      CONCLUSIONS: To our knowledge, this is the first description of a patient with
      HaNDL, confusional symptoms, diffuse slow activity on EEG, and increased blood
      flow velocity in TCD. Our findings suggest a relationship between cerebral
      vasomotor changes and the pathophysiology of HaNDL. TCD may be a useful tool for
      early diagnosis of HaNDL.

PMID- 28427769
TI  - Usefulness of susceptibility-weighted imaging in subacute cerebral fat embolism.

PMID- 28427770
TI  - Intraneural ganglion cyst of the external popliteal sciatic nerve: A possible
      cause of foot drop.

PMID- 28427771
TI  - Locating the site of cerebrospinal fluid leak in a patient with low cerebrospinal
      fluid pressure.

PMID- 28427772
TI  - Seasonal variations of aromatase and estrogen receptors expression in the testis
      of free-ranging sand rats.
AB  - An increasing number of studies revealed the importance of estrogen in male
      reproduction. However, most research was conducted in laboratory rodents
      subjected to standardized environmental conditions. Therefore, seasonal
      regulations of estrogen pathways remain poorly understood under natural
      conditions. Using immunohistochemistry, the expression of several molecules
      involved in the functioning of testis (i.e. 17-beta estradiol [E2], P450
      aromatase, estrogen receptors ESR1, ESR2, and GPER1 [also known as GPR30]) were
      investigated in free-ranging fat sand rats, Psammomys obesus, during the breeding
      and resting seasons. Leydig cells showed a strong immunoreactivity for aromatase
      in the testis sampled during the breeding season only; however, E2, ESR1, ESR2
      and GPER1 were present during both seasons. Sertoli cells showed a positive
      signal for E2 and ESR2 during the breeding season; though, all molecules, except
      GPER1, were present during the resting season. Spermatogonia were reactive for
      E2, ESR2 and GPER1 during the breeding season and for ESR1 and GPER1 during the
      resting season. During both seasons, spermatocytes-I presented a moderate
      reactivity for E2, ESR1, ESR2 and a strong reactivity for GPER1; aromatase was
      detected during the resting season only. Spermatids and spermatozoa were present
      exclusively during breeding season and were reactive for all molecules; except
      round spermatids that were negative for aromatase. The functioning of the testis
      depends on finely tuned stimulation and inhibition systems. Our results suggest
      that differential expression of aromatase, ESR1, ESR2, and GPER1 across cells
      types is involved in the seasonal activation/inactivation cycle of
      spermatogenesis in a free-ranging species.

PMID- 28427773
TI  - Bioturbation transports secondary microplastics to deeper layers in soft marine
      sediments of the northern Baltic Sea.
AB  - Microplastics (MPs) are observed to be present on the seafloor ranging from
      coastal areas to deep seas. Because bioturbation alters the distribution of
      natural particles on inhabited soft bottoms, a mesocosm experiment with common
      benthic invertebrates was conducted to study their effect on the distribution of
      secondary MPs (different-sized pieces of fishing line<1mm). During the study
      period of three weeks, the benthic community increased MP concentration in the
      depth of 1.7-5.1cm in the sediment. The experiment revealed a clear vertical
      gradient in MP distribution with their abundance being highest in the uppermost
      parts of the sediment and decreasing with depth. The Baltic clam Macoma balthica
      was the only study animal that ingested MPs. This study highlights the need to
      further examine the vertical distribution of MPs in natural sediments to reliably
      assess their abundance on the seafloor as well as their potential impacts on
      benthic communities.

PMID- 28427774
TI  - Phosphorus effects on radial oxygen loss, root porosity and iron plaque in two
      mangrove seedlings under cadmium stress.
AB  - Phosphorus is an indispensable element for plants, but its role in alleviating
      the cadmium toxicity of mangrove seedlings is poorly documented. In this study,
      mangrove seedlings were grown in hydroponics and exposed to various Cd and P
      treatments. Data suggested that the inhibitory effect of Cd on the rate of radial
      oxygen loss and root porosity was alleviated by P. A. marina had a higher rate of
      ROL and POR, indicating that it had a stronger adaptability to anaerobic
      environment. K. obovata induced a higher Fe concentration in iron plaque under co
      application of Cd and P, which may relate to higher biomass. Furthermore, P
      increased Cd concentration in iron plaque, implying that iron plaque can be an
      obstacle to prevent Cd entering into the plant, but most Cd was still distributed
      in its roots. These findings highlight a novel mechanism of Cd detoxification
      with P addition in mangrove seedlings.

PMID- 28427775
TI  - Nonoperative management of atypical endometrial hyperplasia and grade 1
      endometrial cancer with the levonorgestrel intrauterine device in medically ill
      post-menopausal women.
AB  - OBJECTIVE: To assess the endometrial response rates to treatment with the
      levonorgestrel intrauterine device in post-menopausal women with atypical
      hyperplasia/endometrial intraepithelial neoplasia and grade 1 endometrioid
      (AH/EC) endometrial carcinoma who are not surgical candidates. METHODS: Chart
      review was undertaken of patients with AH/EC who underwent levonorgestrel
      intrauterine device insertion by a gynecologic oncologist within two academic
      health systems between 2002 and 2013. When available, tissue blocks were
      evaluated with immunohistochemical staining for progesterone receptor expression.
      RESULTS: A total of 41 patients received treatment for AH/EC with the
      levonorgestrel intrauterine device. Follow up sufficient to assess response
      occurred in 36 women (88%). Complete response was documented in 18 of 36 women
      (50%), no response in 8 patients (22%), partial response in 3 women (8%) and
      progression of disease in 7 patients (19%). Four of 18 patients with complete
      response (22%) later experienced relapse of hyperplasia or cancer. Four patients
      (10%) died during the study period: none had evidence of metastatic disease and 1
      of the 4 woman died of perioperative complications following hysterectomy for
      stage I disease. Patients responding to treatment had significantly lower
      progesterone receptor expression on post-treatment biopsies. CONCLUSIONS:
      Intrauterine levonorgestrel is a viable treatment option for post-menopausal
      women with AH/EC who are poor candidates for standard surgical management. The
      response rate in this series is similar to published reports in premenopausal
      patients and includes cases of disease recurrence following conversion to benign
      endometrium.

PMID- 28427777
TI  - Extrapontine Myelinolysis in a Child with Salt Intoxication.

PMID- 28427776
TI  - Autoantibody biomarkers for the detection of serous ovarian cancer.
AB  - : Objective The purpose of this study was to identify a panel of novel serum
      tumor antigen-associated autoantibody (TAAb) biomarkers for the diagnosis of high
      grade serous ovarian cancer. METHODS: To detect TAAb we probed high-density
      programmable protein microarrays (NAPPA) containing 10,247 antigens with sera
      from patients with serous ovarian cancer (n=30 cases/30 healthy controls) and
      measured bound IgG. We identified 735 promising tumor antigens and evaluated
      these with an independent set of serous ovarian cancer sera (n=30 cases/30 benign
      disease controls/30 healthy controls). Thirty-nine potential tumor autoantigens
      were identified and evaluated using an orthogonal programmable ELISA platform
      against a total of 153 sera samples (n=63 cases/30 benign disease controls/60
      healthy controls). Sensitivities at 95% specificity were calculated and a
      classifier for the detection of high-grade serous ovarian cancer was constructed.
      RESULTS: We identified 11-TAAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11,
      TRIM39, UHMK1, KSR1, and NXF3) that distinguished high-grade serous ovarian
      cancer cases from healthy controls with a combined 45% sensitivity at 98%
      specificity. CONCLUSION: These are potential circulating biomarkers for the
      detection of serous ovarian cancer, and warrant confirmation in larger clinical
      cohorts.

PMID- 28427778
TI  - Factors Associated with Delayed Presentation and Misdiagnosis of Testicular
      Torsion: A Case-Control Study.
AB  - We identified factors associated with delay in presentation and misdiagnosis of
      testicular torsion. Compared with acute cases, delayed presentations were more
      likely to report isolated abdominal pain, developmental disorders, and history of
      recent genital trauma. Failure to perform a genitourinary examination or scrotal
      imaging was associated with misdiagnosis.

PMID- 28427779
TI  - Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding
      manifestations: Analysis of 8 clinical studies with selected patient groups on
      omega-3-enriched medical nutrition.
AB  - BACKGROUND & AIMS: The increased consumption of fish oil enriched-products
      exposes a wide diversity of people, including elderly and those with impaired
      health to relatively high amounts of n-3 long-chain polyunsaturated fatty acids
      (n-3 LC-PUFAs). There is an ongoing debate around the possible adverse effects of
      n-3 LC-PUFAs on bleeding risk, particularly relevant in people with a medical
      history of cardiovascular events or using antithrombotic drugs. METHODS: This
      analysis of 8 clinical intervention studies conducted with enteral medical
      nutrition products containing fish oil as a source of n-3 LC-PUFAs addresses the
      occurrence of bleeding-related adverse events and effects on key coagulation
      parameters (Prothrombin Time [PT], (activated) and Partial Thromboplastin Time
      [(a)PTT]). RESULTS: In all the patients considered (over 600 subjects treated
      with the active product in total), with moderate to severe disease, with or
      without concomitant use of antithrombotic agents, at home or in an Intensive Care
      Unit (ICU), no evidence of increased risk of bleeding with use of n-3 LC-PUFAs
      was observed. Furthermore there were no statistically significant changes from
      baseline in measured coagulation parameters. CONCLUSION: These findings further
      support the safe consumption of n-3 LC-PUFAs, even at short-term doses up to 10
      g/day of eicosapentaenoic acid + docosahexaenoic acid (EPA + DHA) or consumed for
      up to 52 weeks above 1.5 g/day, in selected vulnerable and sensitive populations
      such as subjects with gastrointestinal cancer or patients in an ICU. We found no
      evidence to support any concern raised with regards to the application of n-3 LC
      PUFAs and the potentially increased risk for the occurrence of adverse bleeding
      manifestations in these selected patient populations consuming fish oil enriched
      medical nutrition.

PMID- 28427780
TI  - TNM 8th edition: Sentinel Lymph Node Biopsy in stage T1b melanoma.

PMID- 28427781
TI  - Smoking increases the likelihood of Helicobacter pylori treatment failure.
AB  - BACKGROUND AND AIMS: Data regarding the impact of smoking on the success of
      Helicobacter pylori (H. pylori) eradication are conflicting, partially due to the
      fact that sociodemographic status is associated with both smoking and H. pylori
      treatment success. We aimed to assess the effect of smoking on H. pylori
      eradication rates after controlling for sociodemographic confounders. METHODS:
      Included were subjects aged 15 years or older, with a first time positive C13
      urea breath test (C13-UBT) between 2007 to 2014, who underwent a second C13-UBT
      after receiving clarithromycin-based triple therapy. Data regarding age, gender,
      socioeconomic status (SES), smoking (current smokers or "never smoked"), and drug
      use were extracted from the Clalit health maintenance organization database.
      RESULTS: Out of 120,914 subjects with a positive first time C13-UBT, 50,836
      (42.0%) underwent a second C13-UBT test. After excluding former smokers, 48,130
      remained who were eligible for analysis. The mean age was 44.3+/-18.2years, 69.2%
      were females, 87.8% were Jewish and 12.2% Arabs, 25.5% were current smokers. The
      overall eradication failure rates were 33.3%: 34.8% in current smokers and 32.8%
      in subjects who never smoked. In a multivariate analysis, eradication failure was
      positively associated with current smoking (Odds Ratio {OR} 1.15, 95% CI 1.10
      1.20, p<0.001), female gender (OR 1.20, 95% CI 1.14-1.25, p<0.001) and a low
      socioeconomic status (OR 1.24, 95% CI 1.17-1.31, p<0.001). CONCLUSIONS: After
      controlling for socio-demographic confounders, smoking was found to significantly
      increase the likelihood of unsuccessful first-line treatment for H. pylori
      infection.

PMID- 28427782
TI  - Prospective study of a non-restrictive decision rule for acute aortic syndrome.
AB  - OBJECTIVES: To determine the impact of a non-restrictive clinical decision rule
      on CT utilization for Emergency Department patients suspected of having an acute
      aortic syndrome (AAS). METHODS: We prospectively assessed the performance of a
      previously described, collaboratively designed, non-restrictive clinical decision
      rule for AAS. Emergency Department patients with suspected AAS were stratified
      into low and high-risk groups based on decision rule results, from July 2013
      August 2014. Patients with acute trauma, prior AAS or aortic surgery were
      excluded. CT dose reduction protocols were concurrently implemented as a quality
      improvement measure. Bivariate analysis was performed to compare the prospective
      cohort with the historical derivation cohort for CT utilization rates, results of
      CT, AAS incidence and radiation exposure. The performance of the clinical
      decision rule was evaluated. RESULTS: Compared with the historic cohort, the
      study cohort demonstrated a lower CT utilization rate [0.344% (427/124,093)
      versus 0.477% (1465/306,961), (p<0.001)], a trend toward higher CT diagnostic
      yield [4.4% (19/427) versus 2.7% (40/1465), (p=0.08)]. AAS incidence was similar
      [0.015% (19/124,093) versus 0.013% (40/306,961), (p=0.57)]. The mean effective
      radiation dose was markedly lower [12+/-5.5mSv versus 43+/-20mSv, (p<0.0001)].
      The clinical decision rule correctly stratified only 56% (10/18) of patients with
      AAS as high-risk. CONCLUSIONS: A non-restrictive, collaboratively designed,
      clinical decision rule for Emergency Department patients with suspected AAS
      performed poorly in risk-stratifying patients for AAS. However, its
      implementation was associated with a significant and safe decrease in CT
      utilization.

PMID- 28427783
TI  - A trade-off relationship between chest compression depth and chest wall recoil
      during cardiopulmonary resuscitation.

PMID- 28427784
TI  - Prehospital removal improves neurological outcomes in elderly patient with
      foreign body airway obstruction.
AB  - OBJECTIVE: In Japan, the number of patients with foreign body airway obstruction
      by food is rapidly increasing with the increase in the population of the elderly
      and a leading cause of unexpected death. This study aimed to determine the
      factors that influence prognosis of these patients. METHODS: This is a
      retrospective single institutional study. A total of 155 patients were included.
      We collected the variables from the medical records and analyzed them to
      determine the factors associated with patient outcome. Patient outcomes were
      evaluated using cerebral performance categories (CPCs) when patients were
      discharged or transferred to other hospitals. A favorable outcome was defined as
      CPC 1 or 2, and an unfavorable outcome was defined as CPC 3, 4, or 5. RESULTS: A
      higher proportion of patients with favorable outcomes than unfavorable outcomes
      had a witness present at the accident scene (68.8% vs. 44.7%, P=0.0154). Patients
      whose foreign body were removed by a bystander at the accident scene had a
      significantly high rate of favorable outcome than those whose foreign body were
      removed by emergency medical technicians or emergency physician at the scene
      (73.7% vs. 31.8%, P<0.0075) and at the hospital after transfer (73.7% vs. 9.6%,
      P<0.0001). CONCLUSIONS: The presence of a witness to the aspiration and removal
      of the airway obstruction of patients by bystanders at the accident scene
      improves outcomes in patients with foreign body airway obstruction. When airway
      obstruction occurs, bystanders should remove foreign bodies immediately.

PMID- 28427785
TI  - Seeking the Molecular Truth in Bladder Cancer: Biology=Genome*(Transcriptome)2.

PMID- 28427786
TI  - Reply to Philipp Dahm, Vikram Narayan, and Jae Hung Jung's Letter to the Editor
      re: Richard J. Sylvester, Steven E. Canfield, Thomas B.L. Lam, et al. Conflict of
      Evidence: Resolving Discrepancies When Findings from Randomized Controlled Trials
      and Meta-analyses Disagree. Eur Urol 2017;71:811-9.

PMID- 28427787
TI  - Comparing knowledge and self-reported hand hygiene practices with direct
      observation among Iranian hospital nurses.
AB  - We compared knowledge and self-reported hand hygiene practices with direct
      observations among Shiraz Nemazee Hospital nurses. Overall hand hygiene
      compliance was low (39.6%). Use and appreciation for alcohol-based handrubs were
      suboptimal. Some reluctance was due to religious concerns. Most nurses self
      reported performing proper hand hygiene more than 75% of the time, whereas direct
      observation indicated much lower levels of compliance. It appears that additional
      training and improved monitoring are needed.

PMID- 28427788
TI  - Treating complex pancreatic injuries. Trauma and pancreatic surgeons working
      together is the modern management paradigm.

PMID- 28427789
TI  - For a pre-operative assessment of the colon vascular supply.

PMID- 28427791
TI  - In Reply to 'International Normalized Ratio Control in Patients With Atrial
      Fibrillation and CKD'.

PMID- 28427792
TI  - International Normalized Ratio Control in Patients With Atrial Fibrillation and
      CKD.

PMID- 28427790
TI  - Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of
      Exercise to Prevent and Treat Physical Impairments in CKD.
AB  - Patients with chronic kidney disease experience substantial loss of muscle mass,
      weakness, and poor physical performance. As kidney disease progresses, skeletal
      muscle dysfunction forms a common pathway for mobility limitation, loss of
      functional independence, and vulnerability to disease complications. Screening
      for those at high risk for mobility disability by self-reported and objective
      measures of function is an essential first step in developing an
      interdisciplinary approach to treatment that includes rehabilitative therapies
      and counseling on physical activity. Exercise has beneficial effects on systemic
      inflammation, muscle, and physical performance in chronic kidney disease. Kidney
      health providers need to identify patient and care delivery barriers to exercise
      in order to effectively counsel patients on physical activity. A thorough medical
      evaluation and assessment of baseline function using self-reported and objective
      function assessment is essential to guide an effective individualized exercise
      prescription to prevent function decline in persons with kidney disease. This
      review focuses on the impact of kidney disease on skeletal muscle dysfunction in
      the context of the disablement process and reviews screening and treatment
      strategies that kidney health professionals can use in clinical practice to
      prevent functional decline and disability.

PMID- 28427793
TI  - Contribution of health care factors to the burden of skin disease in the United
      States.
AB  - The American Academy of Dermatology has developed an up-to-date national Burden
      of Skin Disease Report on the impact of skin disease on patients and on the US
      population. In this second of 3 manuscripts, data are presented on specific
      health care dimensions that contribute to the overall burden of skin disease.
      Through the use of data derived from medical claims in 2013 for 24 skin disease
      categories, these results indicate that skin disease health care is delivered
      most frequently to the aging US population, who are afflicted with more skin
      diseases than other age groups. Furthermore, the overall cost of skin disease is
      highest within the commercially insured population, and skin disease treatment
      primarily occurs in the outpatient setting. Dermatologists provided approximately
      30% of office visit care and performed nearly 50% of cutaneous surgeries. These
      findings serve as a critical foundation for future discussions on the clinical
      importance of skin disease and the value of dermatologic care across the
      population.

PMID- 28427796
TI  - Molecular methods for septicemia diagnosis.
AB  - Septicemia remains a major cause of hospital mortality. Blood culture remains the
      best approach to identify the etiological microorganisms when a bloodstream
      infection is suspected but it takes long time because it relies on bacterial or
      fungal growth. The introduction in clinical microbiology laboratories of the
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      technology, DNA hybridization, microarrays or rapid PCR-based test significantly
      reduce the time to results. Tests for direct detection in whole blood samples are
      highly desirable because of their potential to identify bloodstream pathogens
      without waiting for blood cultures to become positive. Nonetheless, limitations
      of current molecular diagnostic methods are substantial. This article reviews
      these new molecular approaches (LightCycler SeptiFast, Magicplex sepsis real
      time, Septitest, VYOO, PCR/ESI-MS analysis, T2Candida).

PMID- 28427794
TI  - Occurrence of a novel class 1 integron harboring qnrVC4 in Salmonella Rissen.
AB  - We described qnrVC4 in S. Rissen 166ANSS50, a swine isolate, which was detected
      in the study on quinolone resistance mechanisms of nontyphoidal Salmonella in
      Thailand. The isolate was found to harbor a 17-kb non-conjugative plasmid
      carrying qnrVC4 within 8.91kb of a novel In4-like class 1 integron (In805). It
      contained the multi-drug resistance gene cassettes of qnrVC4-qacH4-aacA4-cmlA7
      blaOXA-10-aadA1-dfrA14 and unusual 3'-CS of mobC-IS6100. This 1014-bp qnrVC4
      cassette included with promoter (PqnrVC4: -35 TTGAGA and -10 TAGTCT) showed high
      homology with qnrVC4 in superintegron of V. cholerae O1 El Tor. The qnrVC4
      recombinant plasmid resulted in 4-, 8-, and 16-fold increase in the MICs of
      nalidixic acid (2-8MUg/mL), ciprofloxacin (0.015-0.125MUg/mL), and norfloxacin
      (0.03-0.5MUg/mL), respectively. In addition, the backbone plasmid revealed a
      novel replicon belonging to the MOBQ1 group from the broad-host-range mobilisable
      IncQ1 plasmid RFS1010 based on relaxase sequences. This is the first known report
      of qnrVC in Salmonella enterica. The qnrVC4 gene was co-transferred with other
      resistance genes via a novel plasmid-borne In805. This allowed the spread of this
      resistance gene to Enterobacteriaceae.

PMID- 28427795
TI  - Reappraisal to the study of 4E-BP1 as an mTOR substrate - A normative critique.
AB  - mTOR-4E-BP1 axis is regarded as the best oncogenic circuitry impinging on
      translational control whereby mTORC1 dictates post-translational regulation of 4E
      BP1. This review provides new insights into the molecular network of signalling
      pathways highlighting the recent explosion of studies in respect to the deviant
      behaviour of 4E-BP1 towards mTORC1. Despite the striking conservation of mTOR
      nexus, the eccentric phosphorylation dynamics of 4E-BP1 negate the apparent
      linear architecture of mTORC1 attesting the importance of other kinases that may
      evoke cross-talks with the conventional frame, most of which are enlisted in the
      manuscript. We also throw light on the tenuous role of rapamycin in 4E-BP1
      regulation, which further necessitates the evaluation of 4E-BP1 to envisage the
      underlying molecular mechanisms in the discovery of novel drugs of 4E-BP1 for new
      treatment strategies. Finally, the review brings forward comprehensive studies
      delineating the redundancy of 4E-BP isoforms in regulating translational control.

PMID- 28427797
TI  - Spectrum of Alpha-1 Antitripsin Deficiency Mutations Detected in Tenerife.

PMID- 28427798
TI  - Reduced post-tonsillectomy bleeding rates through a refined technique.

PMID- 28427799
TI  - Assessing cumulative acute toxicity of chemoradiotherapy in head and neck cancer
      with or without induction chemotherapy.
AB  - BACKGROUND: To compare cumulative acute toxicity in head and neck cancer patients
      treated with concurrent chemoradiotherapy alone (CCRT) versus induction
      chemotherapy (IC) followed by CCRT (I/CCRT). METHODS: 77 patients underwent
      definitive CCRT (30 I/CCRT and 47 CCRT). Toxicity was graded using the Common
      Terminology Criteria for Adverse Events version 4.0. Using the TAME adverse event
      reporting system, short-term toxicity (T) scores were generated for IC (TIC),
      CCRT (TCCRT), total treatment duration (TRx), post-treatment period (TPT) and an
      overall score (Toverall) from treatment start to post treatment period. RESULTS:
      Acute toxicity other than dysphagia, odynophagia, or dermatitis was reported in
      90.0% and 66.0% of I/CCRT and CCRT patients, respectively (P=0.02). Compared to
      CCRT group, I/CCRT patients reported greater mean TRx (TRx: 2.11 vs. 2.87,
      P=0.01) and Toverall (Toverall: 2.60 vs. 3.70, P=0.003). CONCLUSION: I/CCRT
      patients reported more cumulative acute toxicity during treatment compared to
      CCRT patients using the TAME reporting system.

PMID- 28427800
TI  - The effect of OptuneTM Tumor Treating Fields transducer arrays on skin radiation
      dose during radiotherapy.
AB  - A Phase 3 clinical study demonstrated that the addition of 200kHz Tumor Treating
      Fields (TTF) to temozolomide in the post-radiation (RT) phase of therapy in newly
      diagnosed glioblastoma increases progression free and overall survival (resulting
      in FDA and European Union approval). Preclinical studies have demonstrated the
      ability of TTF to act as a radiosensitizer, suggesting concurrent TTF and RT may
      have clinical utility. The removal and replacement of TTF transducer arrays from
      the scalps of patients on a daily basis, i.e., just before and after RT
      treatments, would be extremely cumbersome. Based on these considerations, phantom
      studies of the effect of Optune (TM) transducer arrays on radiation dose
      distribution were performed to evaluate the feasibility of leaving arrays in
      place during RT. Film measurements were performed using Gafchromic EBT3 film and
      an Epson 11000XL scanner. Film calibration was done based on the ratio of the red
      to blue color channel data. A Siemens Oncor linear accelerator operating at 6MV,
      10cm*10cm field size, and 100cm source-to-film distance was used for all
      measurements. For each exposure, two films were stacked, providing planes of
      measurement that were ~0.1 and 0.4mm in depth. Data accrued demonstrated that
      radiation attenuation should not be a clinically significant issue. However, TTF
      transducer arrays were found to cause both a radiation bolus effect, as well as
      an increased exit dose effect. These studies predict increased skin toxicity,
      which merits significant caution for further clinical development of this
      combination.

PMID- 28427801
TI  - [Multimodality imaging in the cardiac catheterization laboratory].
AB  - Cardiac catheterization has greatly contributed to the progress made in the
      management of congenital heart diseases (CHD). Initially used in diagnosis, it
      allowed the understanding of heart diseases, their anatomy and hemodynamics.
      Gradually, the development of interventional cardiology has played a major role
      in the management of these malformations (Patent ductus arteriosus [PDA] and
      atrial septal defect [ASD] closure, pulmonary dilatation, percutaneous pulmonary
      valve implantation...). The development of such technology was made possible
      through the concomitant development of imaging techniques: fluoroscopy,
      ultrasound, MRI and CT. Imaging should provide an accurate view of the lesions,
      the surrounding cardiac structures, as well as medical devices and catheters
      used. Here we address the field of fusion images. The principle of image fusion
      is based on the association by superposition of several imaging techniques: real
      time fluoroscopy and slice imaging performed offline, or ultrasound imaging
      performed simultaneously. The goal is to improve the overall view of the organ,
      its surrounding structures and as the consequence to help the interventional
      cardiologist.

PMID- 28427802
TI  - Deprescription at hospital discharge: Outcomes of a deprescription promoting
      campaign.

PMID- 28427803
TI  - Serum cartilage oligomeric matrix protein levels as a novel non-invasive
      biomarker for liver fibrosis in patients with chronic viral hepatitis? It is too
      early.

PMID- 28427804
TI  - X-ChEXIT in screening for occult cancer in patients with a deep vein thrombosis.

PMID- 28427805
TI  - Confounding, causality, and confusion: the role of intermediate variables in
      interpreting observational studies in obstetrics.
AB  - Prospective and retrospective cohorts and case-control studies are some of the
      most important study designs in epidemiology because, under certain assumptions,
      they can mimic a randomized trial when done well. These assumptions include, but
      are not limited to, properly accounting for 2 important sources of bias:
      confounding and selection bias. While not adjusting the causal association for an
      intermediate variable will yield an unbiased estimate of the exposure-outcome's
      total causal effect, it is often that obstetricians will want to adjust for an
      intermediate variable to assess if the intermediate is the underlying driver of
      the association. Such a practice must be weighed in light of the underlying
      research question and whether such an adjustment is necessary should be carefully
      considered. Gestational age is, by far, the most commonly encountered variable in
      obstetrics that is often mislabeled as a confounder when, in fact, it may be an
      intermediate. If, indeed, gestational age is an intermediate but if mistakenly
      labeled as a confounding variable and consequently adjusted in an analysis, the
      conclusions can be unexpected. The implications of this overadjustment of an
      intermediate as though it were a confounder can render an otherwise persuasive
      study downright meaningless. This commentary provides an exposition of
      confounding bias, collider stratification, and selection biases, with
      applications in obstetrics and perinatal epidemiology.

PMID- 28427806
TI  - Decreased synovial fluid ghrelin levels are linked with disease severity in
      primary knee osteoarthritis patients and are increased following laser therapy.
AB  - BACKGROUND: Ghrelin has been proved to inhibit inflammation and promote cartilage
      growth. So far, its role in patients with primary knee osteoarthritis has not
      been investigated. OBJECTIVE: The current study was performed to explore the
      serum and synovial ghrelin levels as well as the relationship between ghrelin
      levels and disease severity in primary knee OA patients. METHODS: 52 primary knee
      OA patients were recruited in the study. 52 sex and age-matched patients visiting
      our hospital for regular body check were selected as controls. The serum and
      synovial fluid ghrelin levels were examined by enzyme linked immunosorbent assay
      (ELISA) before treatment, one week and four weeks after laser therapy,
      respectively. The inflammation markers IL-6 and TNF-alpha were also investigated.
      The radiographic progression was assessed by Kellgren-Lawrence (K-L) grade scale
      and the symptomatic severity was evaluated by visual analog scale (VAS), Lequesne
      index and Lysholm scores. The Receiver Operating Characteristic (ROC) analysis
      curve was conducted to test the diagnostic value of ghrelin, IL-6 and TNF-alpha
      for radiographic progression. RESULTS: No significant difference of serum ghrelin
      levels was found between knee OA patients and healthy controls. Synovial fluid
      ghrelin concentrations were significantly negatively correlated with K-L grading
      (r=-0.591, P<0.001).Attenuated synovial fluid ghrelin levels were also related to
      clinical severity determined by Lequesne index (r=-0.308, P=0.025),VAS scores (r=
      0.591, P<0.001) and Lysholm scores (r=0.381, P=0.005).In addition, ghrelin levels
      were also negatively associated with TNF-alpha (r=-0.424, P=0.002) and IL-6
      concentrations (r=-0.428, P=0.002). ROC curve analysis demonstrated that ghrelin
      exhibited more diagnostic value than IL-6 and TNF-alpha for assessing
      radiographic progression in medium-late stage. CONCLUSIONS: Decreased synovial
      fluid ghrelin levels are related to disease severity in patients with primary
      osteoarthritis and are increased following laser therapy. Local application of
      ghrelin may serve as an adjunctive therapy for knee OA.

PMID- 28427807
TI  - Targeted Next Generation Sequencing in patients with Myotonia Congenita.
AB  - INTRODUCTION: Myotonia Congenita (MC) is a nondystrophic skeletal muscle disease
      characterized by muscle stiffness, weakness, delayed skeletal relaxation and
      hypertrophic muscle. The disease can be inherited as dominant or recessive. More
      than 130 mutations in CLCN1 gene have been identified. MATERIALS AND METHODS: We
      analyzed the entire coding region and exon-intron boundaries of the CLCN1 gene in
      40 MC patients. Samples already Sanger-sequenced were successively evaluated by
      Next Generation Sequencing (NGS), on Ion Torrent PGM. Moreover, additional 15
      patients were sequenced directly by NGS. RESULTS: NGS allowed us to identify all
      CLCN1 mutations except those located within exon 3, demonstrating a 96% of
      sensitivity. Due to primer design, one SNP (exactly rs7794560) also failed to be
      detected. Our results enlarge the spectrum of CLCN1 mutations and showed a novel
      approach for molecular analysis of MC.

PMID- 28427808
TI  - Rapid, microwave-accelerated synthesis and anti-osteoporosis activities
      evaluation of Morusin scaffolds and Morusignin L scaffolds.
AB  - Described herein is a facile and efficient methodology toward the synthesis of
      Morusin scaffolds and Morusignin L scaffolds 4-9 and 12via a novel three-step
      approach (Michael addition or prenylation, cyclization and cyclization) and use a
      rapid, microwave-accelerated cyclization as the key step. Furthermore, their
      biological activities have been preliminarily demonstrated by in vitro evaluation
      for anti-osteoporosis activity. These Morusin, Morusignin L and newly synthesized
      compounds 5b, 6a, 8e, 8f greatly exhibited the highest potency, especially at the
      10-5mol/L (P<0.01), and had good in vitro anti-osteoporosis activities using the
      commercially available standard drug Ipriflavone as a positive control. The
      mechanisms associated with anti-osteoporosis effects of these compounds may be
      through the inhibition of TRAP enzyme activity and bone resorption in
      osteoclasts, and promotion effect of osteoblast proliferation in vitro. The
      results indicated that Morusin scaffolds and Morusignin L scaffolds may be useful
      leads for further anti-osteoporosis activity screenings.

PMID- 28427809
TI  - Picrasidine G decreases viability of MDA-MB 468 EGFR-overexpressing triple
      negative breast cancer cells through inhibition of EGFR/STAT3 signaling pathway.
AB  - Targeted therapy is unavailable for treating patients with triple-negative breast
      cancer (TNBC), which accounts for approximately 15% of all breast cancers.
      Overexpression of epidermal growth factor receptor (EGFR) is observed in
      approximately 30-60% of TNBCs. Therefore, developing novel strategies for
      inhibiting EGFR signaling is required. In the present study, a natural compound
      library was screened to identify molecules that target TNBCs that overexpress
      EGFR. Picrasidine G (PG), a naturally occurring dimeric alkaloid produced by
      Picrasma quassioides, decreased the viability of the MDA-MB 468 cell line
      (TNBCEGFR+) compared with other breast cancer cell lines. PG treatment increased
      markers of apoptosis, including chromatin condensation, sub-G1 population,
      cleavage of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP). PG
      inhibited the phosphorylation of signal transducer and activator of transcription
      3 (STAT3) and inhibited transcription of the STAT3-target gene encoding survivin.
      Further, PG inhibited EGF-induced STAT3 phosphorylation but not interleukin-6 (IL
      6)-induced STAT3 phosphorylation. These results suggest that PG may contribute to
      the development of targeted therapy of patients with EGFR-overexpressing TNBC.

PMID- 28427810
TI  - Synthesis of novel 5,6-dehydrokawain analogs as osteogenic inducers and their
      action mechanisms.
AB  - An imbalance between bone resorption by osteoclasts and bone formation by
      osteoblasts can cause bone loss and bone-related disease. In a previous search
      for natural products that increase osteogenic activity, we found that 5,6
      dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this
      study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our
      structure-activity relationships revealed that alkylation of para or meta
      position of aromatic ring of 1 promote osteogenic activity. Among the potential
      analogs we synthesized, (E)-6-(4-Ethylstyryl)-4-methoxy-2H-pyran-2-one (14) and
      (E)-6-(4-Butylstyryl)-4-methoxy-2H-pyran-2-one (21) both significantly up
      regulated Runx2 and Osterix mRNA expression at 10uM. These osteogenic activities
      could be mediated by bone morphogenetic protein (BMP) and activation of p38 MAPK
      signaling pathways. Compounds 14 and 21 also inhibited RANKL-induced osteoclast
      differentiation of RAW264 cells. These results indicated that novel 5,6
      dehydrokawain analogs not only increase osteogenic activity but also inhibit
      osteoclast differentiation, and could be potential lead compounds for the
      development of anti-osteoporosis agents.

PMID- 28427811
TI  - New derivatives of ursolic acid through the biotransformation by Bacillus
      megaterium CGMCC 1.1741 as inhibitors on nitric oxide production.
AB  - Microbial transformation of ursolic acid (1) by Bacillus megaterium CGMCC 1.1741
      was investigated and yielded five metabolites identified as 3-oxo-urs-12-en-28
      oic acid (2); 1beta,11alpha-dihydroxy-3-oxo-urs-12-en-28-oic acid (3); 1beta
      hydroxy-3-oxo-urs-12-en-28, 13-lactoe (4); 1beta,3beta, 11alpha-trihydroxyurs-12
      en-28-oic acid (5) and 1beta,11alpha-dihydroxy-3-oxo-urs-12-en-28-O-beta-d
      glucopyranoside (6). Metabolites 3, 4, 5 and 6 were new natural products. Their
      nitric oxide (NO) production inhibitory activity was assessed in
      lipopolysaccharide (LPS) - stimulated RAW 264.7 cells. Compounds 3 and 4
      exhibited significant activities with the IC50 values of 1.243 and 1.711MUM,
      respectively. A primary structure-activity relationship was also discussed.

PMID- 28427812
TI  - Synthesis and evaluation of 4,6-disubstituted pyrimidines as CNS penetrant pan
      muscarinic antagonists with a novel chemotype.
AB  - This letter describes the synthesis and structure activity relationship (SAR)
      studies of structurally novel M4 antagonists, based on a 4,6-disubstituted core,
      identified from a high-throughput screening campaign. A multi-dimensional
      optimization effort enhanced potency at both human and rat M4 (IC50s<300nM), with
      no substantial species differences noted. Moreover, CNS penetration proved
      attractive for this series (brain:plasma Kp,uu=0.87), while other DMPK attributes
      were addressed in the course of the optimization effort, providing low in vivo
      clearance in rat (CLp=5.37mL/min/kg). Surprisingly, this series displayed pan
      muscarinic antagonist activity across M1-5, despite the absence of the
      prototypical basic or quaternary amine moiety, thus offering a new chemotype from
      which to develop a next generation of pan-muscarinic antagonist agents.

PMID- 28427813
TI  - Novel pyrazoles and pyrazolo[1,2-a]pyridazines as selective COX-2 inhibitors;
      Ultrasound-assisted synthesis, biological evaluation, and DFT calculations.
AB  - COX-2 is an inducible enzyme mediating inflammatory responses. Selective
      targeting of COX-2 is useful for developing anti-inflammatory agents devoid of
      ulcerogenic activity. Herein, we report the design and synthesis of a series of
      pyrazoles and pyrazolo[1,2-a]pyridazines with selective COX-2 inhibitory activity
      and in vivo anti-inflammatory effect. Both series were accessed through acid
      catalyzed ultrasound-assisted reactions. The most active compounds in this study
      are two novel molecules, 11 and 16, showing promising selectivity and decent IC50
      of 16.2 and 20.1nM, respectively. These compounds were also docked into the
      crystal structure of COX-2 enzyme (PDB ID: 3LN1) to understand their mode of
      binding. Finally, Mulliken charges and electrostatic surface potential were
      calculated for both compound 11 and celecoxib using DFT method to get insights
      into the molecular determinants of activity of this compound. These results could
      lead to the development of novel COX-2 inhibitors with improved selectivity.

PMID- 28427815
TI  - The Swedish radiological environmental protection regulations applied in a review
      of a license application for a geological repository for spent nuclear fuel.
AB  - For the first time, a system for specific consideration of radiological
      environmental protection has been applied in a major license application in
      Sweden. In 2011 the Swedish Nuclear Fuel & Waste Management Co. (SKB) submitted a
      license application for construction of a geological repository for spent nuclear
      fuel at the Forsmark site. The license application is supported by a post-closure
      safety assessment, which in accordance with regulatory requirements includes an
      assessment of environmental consequences. SKB's environmental risk assessment
      uses the freely available ERICA Tool. Environmental media activity concentrations
      needed as input to the tool are calculated by means of complex biosphere
      modelling based on site-specific information gathered from site investigations,
      as well as from supporting modelling studies and projections of future biosphere
      conditions in response to climate change and land rise due to glacial rebound.
      SKB's application is currently being reviewed by the Swedish Radiation Safety
      Authority (SSM). In addition to a traditional document review with an aim to
      determine whether SKB's models are relevant, correctly implemented and adequately
      parametrized, SSM has performed independent modelling in order to gain confidence
      in the robustness of SKB's assessment. Thus, SSM has used alternative stylized
      reference biosphere models to calculate environmental activity concentrations for
      use in subsequent exposure calculations. Secondly, an alternative dose model
      (RESRAD-BIOTA) is used to calculate doses to biota that are compared with SKB's
      calculations with the ERICA tool. SSM's experience from this review is that
      existing tools for environmental dose assessment are possible to use in order to
      show compliance with Swedish legislation. However, care is needed when site
      representative species are assessed with the aim to contrast them to generic
      reference organism. The alternative modelling of environmental concentrations
      resulted in much lower concentrations compared to SKB's results. However, SSM
      judges that SKB's in this part conservative approach is relevant for a screening
      assessment. SSM also concludes that there are big differences in dose rates
      calculated to different organisms depending on which tool that is used, although
      not systematically higher for either of them. Finally, independent regulatory
      modelling has proven valuable for SSM's review in gaining understanding and
      confidence in SKB's assessment presented in the license application.

PMID- 28427814
TI  - Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing
      substituted 2-oxopiperazines as P1'-P2' ligands.
AB  - We report the design and synthesis of a series of BACE1 inhibitors incorporating
      mono- and bicyclic 6-substituted 2-oxopiperazines as novel P1' and P2' ligands
      and isophthalamide derivative as P2-P3 ligands. Among mono-substituted 2
      oxopiperazines, inhibitor 5a with N-benzyl-2-oxopiperazine and isophthalamide
      showed potent BACE1 inhibitory activity (Ki=2nM). Inhibitor 5g, with N-benzyl-2
      oxopiperazine and substituted indole-derived P2-ligand showed a reduction in
      potency. The X-ray crystal structure of 5g-bound BACE1 was determined and used to
      design a set of disubstituted 2-oxopiperazines and bicyclic derivatives that were
      subsequently investigated. Inhibitor 6j with an oxazolidinone derivative showed a
      BACE1 inhibitory activity of 23nM and cellular EC50 of 80nM.

PMID- 28427816
TI  - Effect of torrefaction on yield and quality of pyrolytic products of arecanut
      husk: An agro-processing wastes.
AB  - In the present study, arecanut husk, an agro-processing waste of areca plam
      industry highly prevalent in the north-eastern region of India, was investigated
      for its suitability as a prospective bioenergy feedstock for thermo-chemical
      conversion. Pretreatment of areca husk using torrefaction was performed in a
      fixed bed reactor with varying reaction temperature (200, 225, 250 and 275
      degrees C). The torrefied areca husk was subsequently pyrolyzed from temperature
      range of 300-600 degrees C with heating rate of 40 degrees C/min to obtain biooil
      and biochar. The torrefied areca husk, pyrolysis products were characterized by
      using different techniques. The energy and mass yield of torrefied biomass were
      found to be decreased with an increase in the torrefaction temperature. Further,
      biochar were found to be effective in removal of As (V) from aqueous solutions
      but efficiency of removal was better in case of torrefied biochar. Chemical
      composition of bio-oil is also influenced by torrefaction process.

PMID- 28427817
TI  - Reducing discrepancies between 3D and 2D simulations due to cell packing density.
AB  - Modelling all three spatial dimensions is often much more computationally
      expensive than modelling a two-dimensional simplification of the same system.
      Researchers comparing these approaches in individual-based models of microbial
      biofilms report quantitative, but not qualitative, differences between 2D and 3D
      simulations. We show that a large part of the discrepancy is due to the different
      space packing densities of circles versus spheres, and demonstrate methods to
      compensate for this: the internal density of individuals or the distances between
      them can be scaled. This result is likely to be useful in similar models, such as
      smoothed particle hydrodynamics.

PMID- 28427818
TI  - A necessary condition for dispersal driven growth of populations with discrete
      patch dynamics.
AB  - We revisit the question of when can dispersal-induced coupling between discrete
      sink populations cause overall population growth? Such a phenomenon is called
      dispersal driven growth and provides a simple explanation of how dispersal can
      allow populations to persist across discrete, spatially heterogeneous,
      environments even when individual patches are adverse or unfavourable. For two
      classes of mathematical models, one linear and one non-linear, we provide
      necessary conditions for dispersal driven growth in terms of the non-existence of
      a common linear Lyapunov function, which we describe. Our approach draws heavily
      upon the underlying positive dynamical systems structure. Our results apply to
      both discrete- and continuous-time models. The theory is illustrated with
      examples and both biological and mathematical conclusions are drawn.

PMID- 28427819
TI  - Size-dependent axial instability of microtubules surrounded by cytoplasm of a
      living cell based on nonlocal strain gradient elasticity theory.
AB  - Microtubules including tubulin heterodimers arranging in a parallel shape of
      cylindrical hollow plays an important role in the mechanical stiffness of a
      living cell. In the present study, the nonlocal strain gradient theory of
      elasticity including simultaneously the both nonlocality and strain gradient size
      dependency is put to use within the framework of a refined orthotropic shell
      theory with hyperbolic distribution of shear deformation to analyze the size
      dependent buckling and postbuckling characteristics of microtubules embedded in
      cytoplasm under axial compressive load. The non-classical governing differential
      equations are deduced via boundary layer theory of shell buckling incorporating
      the nonlinear prebuckling deformation and microtubule-cytoplasm interaction in
      the living cell environment. Finally, with the aid of a two-stepped perturbation
      solution methodology, the explicit analytical expressions for nonlocal strain
      gradient stability paths of axially loaded microtubules are achieved. It is
      illustrated that by taking the nonlocal size effect into consideration, the
      critical buckling load of microtubule and its maximum deflection associated with
      the minimum postbuckling load decreases, while the strain gradient size
      dependency causes to increase them.

PMID- 28427820
TI  - The ovariectomized mouse simulates the pathophysiology of postmenopausal female
      pattern hair loss.

PMID- 28427821
TI  - A case of recessive dystrophic epidermolysis bullosa with a novel
      c.6885_6898del14 mutation in the COL7A1 gene.

PMID- 28427822
TI  - Reassessment of the clinical significance of portal-superior mesenteric vein
      invasion in borderline resectable pancreatic cancer.
AB  - OBJECTIVE: The principal objective of this study is to clarify the prognostic
      significance of borderline resectable pancreatic cancer (BRPC). The second
      objective is to evaluate the prognostic impact of the depth of pathological
      venous invasion. METHODS: The study included 122 pancreatic cancer patients who
      underwent curative surgery. All computed tomography scans of the patients were
      retrospectively interpreted and classified according to the NCCN guidelines,
      version 1.2016, as resectable (-) or borderline resectable (+) in each arterial
      (BR-A) and venous (BR-PV) involvement. RESULTS: The overall survival (OS) rate
      was significantly higher in BR-A(-) patients (n = 94) than in BR-A(+) patients (n
      = 28) (P = 0.001), whereas there was no difference between BR-PV(-) (n = 101) and
      BR-PV(+) patients (n = 21) (P = 0.257). In a multivariate analysis, the
      independent predictors of OS included BR-A(+) (P = 0.002), lymph node metastasis
      (P = 0.008), pathological venous invasion (P = 0.003), and adjuvant chemotherapy
      (P = 0.001). Of 39 patients who underwent venous resection, no significant
      difference was observed between BR-PV(-) (n = 20) and BR-PV(+) patients (n = 19)
      in resection rate, lymph node metastasis, the presence of extrapancreatic nerve
      invasion, recurrence rate, frequency of initial recurrence at a liver or local
      site, and OS. Pathological venous invasion was significantly deeper in BR-PV(+)
      patients. However, the depth of invasion was not associated with OS. CONCLUSION:
      The definition of venous involvement in the current guidelines predicted the
      depth of pathological venous invasion but not OS in BRPC patients. Further
      prospective, randomized studies are needed to establish treatment strategies for
      BRPC patients with isolated venous involvement.

PMID- 28427823
TI  - Journey of hybrid procedures in peripheral vascular diseases.

PMID- 28427824
TI  - Association between monocyte chemoattractant protein-1 -2518 A/G gene
      polymorphism and the outcome of the nonsurgical periodontal treatment.
AB  - BACKGROUND/PURPOSE: Elevated monocyte chemoattractant protein-1 (MCP-1) is
      related to severe periodontal destruction. Furthermore, MCP-1 -2518 A/G gene
      polymorphism affects MCP-1 after inflammatory stimuli. This study analyzed the
      association between MCP-1 -2518 gene polymorphism and the outcome of nonsurgical
      periodontal treatment. METHODS: Forty periodontal patients were recruited and MCP
      1 -2518 A/G gene polymorphisms were analyzed using polymerase chain reaction
      restriction fragment length polymorphism assay. The clinical periodontal
      parameters, including probing depth (PD), clinical attachment level (CAL),
      gingival index (GI), bleeding index (BI) and plaque index (PI), were recorded
      before and six weeks after nonsurgical periodontal therapy. Patients were divided
      into chronic periodontitis (CP) or aggressive periodontitis (AP). Multiple linear
      regression analysis was performed to investigate certain predictors of the
      therapy outcome. RESULTS: The frequency of MCP-1 -2518 genotype-positive
      (carrying allele G) was 42.5%. Poor treatment outcome in PD, GI and BI
      improvement could be predicted with MCP-1 -2518 A/G genotype and aggressive
      periodontitis status as the predictor variables. In contrast, MCP-1 -2518 A/A
      genotype and aggressive periodontitis status could predict better treatment
      response in PD and BI improvement. However, MCP-1 -2518 genotype did not affect
      the treatment outcome in patients with chronic periodontitis. CONCLUSION: MCP-1 
      2518 A/G genotype might be useful in predicting less favorable nonsurgical
      treatment outcome in patients with aggressive periodontitis. However, MCP-1 -2518
      gene polymorphism may not play a role in patients with chronic periodontitis.
      This study suggests that MCP-1 -2518 genotype may influence the outcome of
      nonsurgical periodontal treatment in aggressive periodontitis patients.

PMID- 28427825
TI  - Molecular mechanisms of the yeast adaptive response and tolerance to stresses
      encountered during ethanol fermentation.
AB  - During ethanol fermentation, yeast cells encounter various stresses including
      sugar substrates-induced high osmolarity, increased ethanol concentration, oxygen
      metabolism-derived reactive oxygen species (ROS), and elevated temperature. To
      cope with these fermentation-associated stresses, appropriate adaptive responses
      are required to prevent stress-induced cellular dysfunctions and to acquire
      stress tolerances. This review will focus on the cellular effects of these
      stresses, molecular basis of the adaptive response to each stress, and the
      cellular mechanisms contributing to stress tolerance. Since a single stress can
      cause diverse effects, including specific and non-specific effects, both specific
      and general stress responses are needed for achieving comprehensive protection.
      For instance, the high-osmolarity glycerol (HOG) pathway and the Yap1/Skn7
      mediated pathways are specifically involved in responses to osmotic and oxidative
      stresses, respectively. On the other hand, due to the common effect of these
      stresses on disturbing protein structures, the upregulation of heat shock
      proteins (HSPs) and trehalose is induced upon exposures to all of these stresses.
      A better understanding of molecular mechanisms underlying yeast tolerance to
      these fermentation-associated stresses is essential for improvement of yeast
      stress tolerance by genetic engineering approaches.

PMID- 28427826
TI  - Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase
      III Randomized Controlled Clinical Trials.
AB  - OBJECTIVE: Suvorexant is an orexin receptor antagonist approved for treating
      insomnia at doses of 10-20 mg. Previously reported phase III results showed that
      suvorexant was effective and well-tolerated in a combined-age population (elderly
      and nonelderly adults). The present analysis evaluated the clinical profile of
      suvorexant specifically in the elderly. METHODS: Prespecified subgroup analyses
      of pooled 3-month data from two (efficacy) and three (safety) randomized, double
      blind, placebo-controlled, parallel-group trials. In each trial, elderly (>=65
      years) patients with insomnia were randomized to suvorexant 30 mg, suvorexant 15
      mg, and placebo. By design, fewer patients were randomized to 15 mg. Patient
      reported and polysomnographic (subset of patients) sleep maintenance and onset
      endpoints were measured. RESULTS: Suvorexant 30 mg (N = 319) was effective
      compared with placebo (N = 318) on patient-reported and polysomnographic sleep
      maintenance, and onset endpoints at Night 1 (polysomnographic endpoints)/Week 1
      (patient-reported endpoints), Month 1, and Month 3. Suvorexant 15 mg (N = 202
      treated) was also effective across these measures, although the onset effect was
      less evident at later time points. The percentages of patients discontinuing
      because of adverse events over 3 months were 6.4% for 30 mg (N = 627 treated),
      3.5% for 15 mg (N = 202 treated), and 5.5% for placebo (N = 469 treated).
      Somnolence was the most common adverse event (8.8% for 30 mg, 5.4% for 15 mg,
      3.2% for placebo). CONCLUSION: Suvorexant generally improved sleep maintenance
      and onset over 3 months of nightly treatment and was well-tolerated in elderly
      patients with insomnia (clinicaltrials.gov; NCT01097616, NCT01097629,
      NCT01021813).

PMID- 28427827
TI  - Antiviral screen identifies EV71 inhibitors and reveals camptothecin-target, DNA
      topoisomerase 1 as a novel EV71 host factor.
AB  - Enterovirus 71 (EV71) is one of the causative agents of hand, foot and mouth
      disease (HFMD) associated with severe neurological disease. EV71's pathogenesis
      remains poorly understood and the lack of approved antiviral has led to its
      emergence as a clinically important neurotropic virus. The goals of this study
      were to: (i) identify novel anti-EV71 compounds that may serve as lead molecules
      for therapeutics; and (ii) investigate their targets in downstream studies. We
      screened a 502-compound library of highly purified natural products for anti-EV71
      activities in a cell-based immunofluorescence assay that were then confirmed in
      viral plaque reduction assays. Along with known antivirals, novel inhibitors of
      EV71 were also identified. We selected camptothecin for downstream studies and
      found that it is a limited spectrum enterovirus inhibitor that inhibits
      coxsackievirus A16 but not ECHOvirus 7. Camptothecin, a DNA topoisomerase 1
      (TOP1) inhibitor, inhibits both viral RNA replication and translation based on
      luciferase replicon studies. Depletion of TOP1 using siRNA was then able to
      rescue EV71 infection from camptothecin inhibition. Interestingly, EV71 viral RNA
      replication and translation were also in TOP1 depleted cells. We found that
      nuclear TOP1 was relocalized to cytoplasmic replication vesicles during EV71
      infection and localized with viral 3CD using confocal microscopy and proximity
      ligation assays. Our findings reveal camptothecin to be a limited spectrum
      antiviral against enteroviruses that functions in a TOP1-dependent but
      cytotoxicity-independent manner. TOP1 is in turn needed for maximal EV71 viral
      RNA replication and viral protein synthesis.

PMID- 28427828
TI  - A combined Clostridium perfringens/Trueperella pyogenes inactivated vaccine
      induces complete immunoprotection in a mouse model.
AB  - Clostridium perfringens (C. perfringens) and Trueperella pyogenes (T. pyogenes)
      are two bacterial pathogens frequently associated with wound infections and
      following lethal complications in livestock. However, prudent use of
      antimicrobial agents is highly required given the emergence of multidrug
      resistant strains of both bacteria and need for food safety. In the current
      study, a combined vaccine, composed of inactivated C. perfringens and T.
      pyogenes, was prepared. The amount of formaldehyde being used to inactivate two
      bacteria was optimized to retain the immunogenicity of antigens. Three adjuvants
      were tested for their potency in improving specific immune responses against the
      candidate antigens. Then inactivated combined C. perfringens/T. pyogenes vaccine
      was prepared using inactive cultures of two organisms. The ratio of inactive
      cultures of two organisms for preparation of combined vaccine was optimized to
      gain effective protective immunity against the two pathogens. Results revealed
      that combined C. perfringens/T. pyogenes inactive vaccine can elicit high level
      of exotoxins and cell-associated antigen-specific antibodies and induce complete
      protection against C. perfringens and T. pyogenes infections in mice. The
      combined vaccine could be used as an alternative of antibiotics for prevention of
      C. perfringens and T. pyogenes infections in animals.

PMID- 28427829
TI  - Systematic review and meta-analysis of hepatic resection versus transarterial
      chemoembolization for solitary large hepatocellular carcinoma.
AB  - BACKGROUND: Surgical techniques and pre-operative patient evaluation have
      improved since the initial development of the Barcelona clinic liver cancer
      staging system. The optimal treatment for solitary hepatocellular carcinoma >=5
      cm remains unclear. The aim of this study was to review the long-term survival
      outcomes of hepatic resection versus transarterial chemoembolisation (TACE) for
      solitary large tumours. METHODS: EMBASE, MEDLINE, Pubmed and the Cochrane
      database were searched for studies comparing resection with TACE for solitary HCC
      >=5 cm. The primary outcome was overall survival at 1, 3 and 5 years. RESULTS:
      The meta-analysis combined the results of four cohort studies including 861
      patients where 452 underwent hepatic resection and 409 were treated with TACE to
      an absence of viable tumour. The pooled HR for 3 year OS rate calculated using
      the random effects model was 0.60 (95% CI 0.46-0.79, p < 0.001; I2 = 54%, P =
      0.087). The pooled HR for 5 year OS rate calculated using the random effects
      model was 0.59 (95% CI 0.43-0.81, p = 0.001; I2 = 80%, P = 0.002). CONCLUSION:
      Hepatic resection has been shown to result in greater survivability and time to
      disease progression than TACE for solitary HCC >=5 cm. Where a patient is fit for
      surgery, has adequate liver function and a favourable tumour, resection should be
      considered.

PMID- 28427830
TI  - Liver transplantation for hereditary hemorrhagic telangiectasia: a systematic
      review.
AB  - AIM: To evaluate the indications, timing and results of liver transplantation in
      patients affected by hereditary hemorrhagic telangiectasia (HHT), by undertaking
      a systematic review of the current literature. METHODS: Electronic
      bibliographical databases were searched on MEDLINE and Pubmed according to the
      PRISMA criteria. A total of 58 articles were initially found, 11 have been
      excluded because of single center series later included in the European Liver
      transplant Registry (ELTR), already reported in this study. Thirty-eight articles
      have been excluded because they did not report specifically new cases of liver
      transplantation for hereditary hemorrhagic telangiectasia. Finally 9 articles
      were included in the analysis. RESULTS: A total of 56 patients who underwent
      liver transplantation for HHT are present in the English literature. One
      additional patient is presented in this article, for a total of 57 patients
      worldwide. To date, the most consistent published series is the one of the ELTR,
      including patients from 15 liver transplantation centers in the period 1985-2003
      with a mean follow-up of 69 months. Ten-year patient and graft survival is 82.5%
      CONCLUSION: Liver transplantation should be considered as a radical but
      definitive treatment option in patients affected by HHT with liver or cardiac
      involvement not responsive to medical treatment.

PMID- 28427831
TI  - Prevalence of abdominal obesity among Chinese adults in 2011.
AB  - BACKGROUND: The prevalence of abdominal obesity is increasing dramatically
      worldwide. This study aimed to estimate the current prevalence of abdominal
      obesity from the 2011 China Health and Nutrition Survey (CHNS) and compare the
      data with other countries. METHODS: Waist circumference (WC) of 12,326 Chinese
      adults (aged 20 years or older) from the 2011 CHNS were analyzed by age group and
      region. Abdominal obesity was defined as a WC >=90 cm for men and WC >=80 cm for
      women based on World Health Organization (WHO) recommendations for Asians.
      RESULTS: In 2011, the age-adjusted mean WC was 85.9 cm (95% confidence interval
      [CI], 85.6-86.2 cm) for men and 80.7 cm (95% CI, 80.4-80.9 cm) for women. Based
      on the WHO recommendations, the age-adjusted prevalence of abdominal obesity was
      44.0% (95% CI, 43.1%-44.8%) overall, 35.3% (95% CI, 34.1%-36.6%) in men, and
      51.7% (95% CI, 50.5%-52.9%) in women. Moreover, the age-adjusted prevalence was
      44.0% (95% CI, 42.7%-45.2%) in rural populations, 42.5% (95% CI, 40.7%-44.2%) in
      urban populations, and 45.2% (95% CI, 43.5%-46.9%) in megacity populations. The
      prevalence in China (35.3% for men and 51.7% for women) was lower than in Japan
      (50.8% for men) and the United States (43.5% for men and 64.7% for women).
      Similar results were observed when applying the criteria suggested by the Working
      Group on Obesity in China. CONCLUSIONS: In 2011, the age-adjusted prevalence of
      abdominal obesity in China was 35.3% in men and 51.7% in women.

PMID- 28427832
TI  - [When a cardiac valvular affectation can guide to the diagnosis of a malignant
      tumor?]

PMID- 28427833
TI  - A European research network to improve diagnosis, treatment and care for patients
      with persistent somatic symptoms: Work report of the EURONET-SOMA conference
      series.

PMID- 28427834
TI  - Doped silica fibre thermoluminescence measurements of radiation dose in the use
      of 223Ra.
AB  - Using tailor-made sub-mm dimension doped-silica fibres, thermoluminescent
      dosimetric studies have been performed for alpha-emitting sources of 223RaCl2
      (the basis of the Bayer Healthcare product Xofigo(r)). The use of 223RaCl2 in the
      palliative treatment of bone metastases resulting from late-stage castration
      resistant prostate cancer focuses on its favourable uptake in metabolically
      active bone metastases. Such treatment benefits from the high linear energy
      transfer (LET) and associated short path length (<100um) of the alpha-particles
      emitted by 223Ra and its decay progeny. In seeking to provide for in vitro
      dosimetry of the alpha-particles originating from the 223Ra decay series,
      investigation has been made of the TL yield of various forms of Ge-doped SiO2
      fibres, including photonic crystal fibre (PCF) collapsed, PCF uncollapsed, flat
      and single-mode fibres. Irradiations of the fibres were performed at the UK
      National Physical Laboratory (NPL). Notable features are the considerable
      sensitivity of the dosimeters and an effective atomic number Zeff approaching
      that of bone, the glass fibres offering the added advantage of being able to be
      placed directly into liquid. The outcome of present research is expected to
      inform development of doped fibre dosimeters of versatile utility, including for
      applications as detailed herein.

PMID- 28427835
TI  - Maxillofacial growth and speech outcome after one-stage or two-stage palatoplasty
      in unilateral cleft lip and palate. A systematic review.
AB  - BACKGROUND: The number of surgical procedures to repair a cleft palate may play a
      role in the outcome for maxillofacial growth and speech. The aim of this
      systematic review was to investigate the relationship between the number of
      surgical procedures performed to repair the cleft palate and maxillofacial
      growth, speech and fistula formation in non-syndromic patients with unilateral
      cleft lip and palate. MATERIAL AND METHODS: An electronic search was performed in
      PubMed/old MEDLINE, the Cochrane Library, EMBASE, Scopus and CINAHL databases for
      publications between 1960 and December 2015. Publications before 1950-journals of
      plastic and maxillofacial surgery-were hand searched. Additional hand searches
      were performed on studies mentioned in the reference lists of relevant articles.
      Search terms included unilateral, cleft lip and/or palate and palatoplasty. Two
      reviewers assessed eligibility for inclusion, extracted data, applied quality
      indicators and graded level of evidence. RESULTS: Twenty-six studies met the
      inclusion criteria. All were retrospective and non-randomized comparisons of one-
      and two-stage palatoplasty. The methodological quality of most of the studies was
      graded moderate to low. The outcomes concerned the comparison of one- and two
      stage palatoplasty with respect to growth of the mandible, maxilla and cranial
      base, and speech and fistula formation. CONCLUSIONS: Due to the lack of high
      quality studies there is no conclusive evidence of a relationship between one- or
      two-stage palatoplasty and facial growth, speech and fistula formation in
      patients with unilateral cleft lip and palate.

PMID- 28427836
TI  - Adherence to continuous positive airway pressure in adults with an intellectual
      disability.
AB  - STUDY OBJECTIVES: This retrospective study evaluated the feasibility of
      continuous positive airway pressure (CPAP) therapy in adults with intellectual
      disabilities (ID). METHODS: CPAP therapy of 24 obstructive sleep apnea syndrome
      (OSA) patients with ID were compared to age- and sex-matched adults with normal
      cognitive functioning. All ID patients received an intensive in-hospital training
      protocol to stimulate adherence. Good adherence was defined as a use of >70% of
      the nights and >4 h/night. Influencing factors were assessed. RESULTS: Baseline
      apnea-hypopnea index (AHI) was significantly higher in ID patients compared to
      controls (median 34/h (range 6-101) versus 17/h (range 5-50), p = 0.013). The
      required average duration of in-hospital training was four nights (range 1-8
      days). At six weeks, 60% of the ID patients showed good adherence and 65% at six
      months, compared to 71% and 50% respectively in the control group. Mean CPAP use
      per night was equal in both groups both at six weeks (5 h in both groups) and six
      months (ID 6:30 h vs control 5 h (p = 0.18)). CPAP adherence correlated with
      baseline AHI in the control patients, but not in ID patients. There was no
      correlation between CPAP adherence and the level of ID or the degree of support
      at home. CONCLUSIONS: Using an intensive training protocol it is very well
      feasible to apply CPAP therapy in OSA patients with any degree of ID. CPAP
      adherence in ID patients was comparable to the control patients in this study as
      well as to previously published adherence numbers.

PMID- 28427837
TI  - In vitro fatigue tests and in silico finite element analysis of dental implants
      with different fixture/abutment joint types using computer-aided design models.
AB  - PURPOSE: The aim of this study was to evaluate fatigue resistance of dental
      fixtures with two different fixture-abutment connections by in vitro fatigue
      testing and in silico three-dimensional finite element analysis (3D FEA) using
      original computer-aided design (CAD) models. METHODS: Dental implant fixtures
      with external connection (EX) or internal connection (IN) abutments were
      fabricated from original CAD models using grade IV titanium and step-stress
      accelerated life testing was performed. Fatigue cycles and loads were assessed by
      Weibull analysis, and fatigue cracking was observed by micro-computed tomography
      and a stereomicroscope with high dynamic range software. Using the same CAD
      models, displacement vectors of implant components were also analyzed by 3D FEA.
      Angles of the fractured line occurring at fixture platforms in vitro and of
      displacement vectors corresponding to the fractured line in silico were compared
      by two-way ANOVA. RESULTS: Fatigue testing showed significantly greater
      reliability for IN than EX (p<0.001). Fatigue crack initiation was primarily
      observed at implant fixture platforms. FEA demonstrated that crack lines of both
      implant systems in vitro were observed in the same direction as displacement
      vectors of the implant fixtures in silico. CONCLUSIONS: In silico displacement
      vectors in the implant fixture are insightful for geometric development of dental
      implants to reduce complex interactions leading to fatigue failure.

PMID- 28427838
TI  - Stratification strategy for evaluating the influence of diabetes complication
      severity index on the risk of hospitalization: a record linkage data in Western
      Australia.
AB  - OBJECTIVE: This study aimed to develop a risk stratification strategy for
      evaluating the relationship between complications of diabetes and the risk of
      diabetic-related hospitalization to accurately classify diabetes severity.
      METHODS: The study used administrative health records for 40,624 individuals with
      diabetes aged >=18years in Western Australian. The adapted Diabetes Complication
      Severity Index (DCSI), socio-demographic and clinical characteristics were used
      in random effects negative binomial and threshold effect models to determine the
      optimal stratification strategy for diabetes severity based on the homogeneity of
      the risk of hospitalization in response to variation of the DCSI. RESULTS: The
      optimal stratification of people with diabetes was specified by four sub
      populations. The first sub-population was no complications with an inverse
      association with the risk of hospitalizations (coefficient-0.247, SE 0.03).
      Further three sub-populations with DCSI at one (coefficient 0.289, SE 0.01), two
      (coefficient 0.339, SE 0.01) and three or more (coefficient 0.381, SE 0.01) were
      used to accurately describe the impact of DCSI on the risk of hospitalization.
      CONCLUSION: A stratification into four subpopulations based on the homogeneous
      impact of diabetes DCSI on the risk of hospitalization may be more suitable for
      evaluating health care interventions and planning health care provision.

PMID- 28427839
TI  - The prevalence of metabolic syndrome among older adults in Ecuador: Results of
      the SABE survey.
AB  - AIMS: To describe the prevalence of metabolic syndrome among older adults in
      Ecuador. A secondary objective was to examine the relationship between metabolic
      syndrome and its components and insulin resistance among non-diabetic
      participants. MATERIALS AND METHODS: The National Survey of Health, Wellbeing,
      and Aging survey was used to examine the prevalence of metabolic syndrome
      according to demographic, behavioral, and health characteristics of the
      participants. Logistic regression models adjusted for covariates were used to
      examine the independent association of metabolic syndrome and its components and
      insulin resistance in non-diabetic older adults. RESULTS: Of 2298 participants
      with a mean age of 71.6 (SD 8.1) years, the prevalence of metabolic syndrome was
      66.0% (95% CI, 62.6%, 69.3%) in women and 47.1% (95% CI, 43.2%, 50.9) in men.
      However, even higher prevalence rates were seen among literate individuals,
      residents from urban areas of the coastal and Andes Mountains region, obese
      subjects, those diagnosed with diabetes, and participants with>=2 comorbidities.
      Overall, abdominal obesity followed by elevated blood pressure were the metabolic
      syndrome components more prevalent and associated with insulin resistance among
      older Ecuadorians. Moreover, after adjustment for covariates, older adults
      defined as having metabolic syndrome had a 3-fold higher odds of having insulin
      resistance as compared with those without. CONCLUSIONS: The prevalence of
      metabolic syndrome is high among older adults in Ecuador. The present findings
      may assist public health authorities to implement programs of lifestyle and
      behavioral modification targeting older adults at increased risk for this cardio
      metabolic disorder.

PMID- 28427840
TI  - AAV-ID: A Rapid and Robust Assay for Batch-to-Batch Consistency Evaluation of AAV
      Preparations.
AB  - Adeno-associated virus (AAV) vectors are promising clinical candidates for
      therapeutic gene transfer, and a number of AAV-based drugs may emerge on the
      market over the coming years. To insure the consistency in efficacy and safety of
      any drug vial that reaches the patient, regulatory agencies require extensive
      characterization of the final product. Identity is a key characteristic of a
      therapeutic product, as it ensures its proper labeling and batch-to-batch
      consistency. Currently, there is no facile, fast, and robust characterization
      assay enabling to probe the identity of AAV products at the protein level. Here,
      we investigated whether the thermostability of AAV particles could inform us on
      the composition of vector preparations. AAV-ID, an assay based on differential
      scanning fluorimetry (DSF), was evaluated in two AAV research laboratories for
      specificity, sensitivity, and reproducibility, for six different serotypes (AAV1,
      2, 5, 6.2, 8, and 9), using 67 randomly selected AAV preparations. In addition to
      enabling discrimination of AAV serotypes based on their melting temperatures, the
      obtained fluorescent fingerprints also provided information on sample
      homogeneity, particle concentration, and buffer composition. Our data support the
      use of AAV-ID as a reproducible, fast, and low-cost method to ensure batch-to
      batch consistency in manufacturing facilities and academic laboratories.

PMID- 28427841
TI  - Localized shape abnormalities in the thalamus and pallidum are associated with
      secondarily generalized seizures in mesial temporal lobe epilepsy.
AB  - Mesial temporal lobe epilepsy (mTLE) is a common type of drug-resistant epilepsy
      and secondarily generalized tonic-clonic seizures (sGTCS) have devastating
      consequences for patients' safety and quality of life. To probe the mechanism
      underlying the genesis of sGTCS, we investigated the structural differences
      between patients with and without sGTCS in a cohort of mTLE with radiologically
      defined unilateral hippocampal sclerosis. We performed voxel-based morphometric
      analysis of cortex and vertex-wise shape analysis of subcortical structures (the
      basal ganglia and thalamus) on MRI of 39 patients (21 with and 18 without sGTCS).
      Comparisons were initially made between sGTCS and non-sGTCS groups, and
      subsequently made between uncontrolled-sGTCS and controlled-sGTCS subgroups.
      Regional atrophy of the ipsilateral ventral pallidum (cluster size=450 voxels,
      corrected p=0.047, Max voxel coordinate=107, 120, 65), medial thalamus (cluster
      size=1128 voxels, corrected p=0.049, Max voxel coordinate=107, 93, 67), middle
      frontal gyrus (cluster size=60 voxels, corrected p<0.05, Max voxel coordinate=
      30, 49.5, 6), and contralateral posterior cingulate cortex (cluster size=130
      voxels, corrected p<0.05, Max voxel coordinate=16.5, -57, 27) was found in the
      sGTCS group relative to the non-sGTCS group. Furthermore, the uncontrolled-sGTCS
      subgroup showed more pronounced atrophy of the ipsilateral medial thalamus
      (cluster size=1240 voxels, corrected p=0.014, Max voxel coordinate=107, 93, 67)
      than the controlled-sGTCS subgroup. These findings indicate a central role of
      thalamus and pallidum in the pathophysiology of sGTCS in mTLE.

PMID- 28427843
TI  - Relative importance of different exposure routes of heavy metals for humans
      living near a municipal solid waste incinerator.
AB  - The potential health effects of toxic chemicals (e.g. heavy metals) emitted by
      municipal solid waste incinerators (MSWIs) are of great concern to local
      residents, however there have been few studies on the contributions of different
      exposure pathways and their subsequent effects on the body burden of residents
      living near MSWIs. In this study, multiple exposure routes of heavy metals
      including Pb, Cr, Cd and Mn were assessed by investigating the metals in foods
      (such as vegetables, crops, meats and fruits etc.), drinking water, ambient air
      and soil collected surrounding an MSWI in Shenzhen, south China. Vegetable
      ingestion played the most important role in the total average daily dose of Pb
      and Cr, and cereals were the key exposure routes for Mn and Cd. Compound-specific
      contaminations were observed in the investigated areas, with Pb and Cr present in
      the surrounding environment, having accumulated to relatively high levels in the
      local vegetables, and the intake of contaminated vegetable foods greatly
      influencing the body burden of Pb and Cr. Consistently, significantly high blood
      concentrations of Pb and Cr were detected in the local residents compared to a
      referenced population, and a lack of significant differences was found for Cd and
      Mn. The results possibly suggested that emission of MSWI influenced the external
      exposure doses of the major pathways of Pb and Cr in this study, and resulted in
      the different body burden of metals in humans living near a MSWI. MSWI-local food
      humans is an important exposure pathway for residents living near MSWI, and thus
      should not be neglected in developing future strategies and policies to prevent
      the high risks suffered by residents living near MSWIs.

PMID- 28427842
TI  - Predominance of international clone 2 OXA-23-producing-Acinetobacter baumannii
      clinical isolates in Greece, 2015: results of a nationwide study.
AB  - In a previous nationwide study in Greece, OXA-58 was the sole carbapenemase
      present among carbapenem-resistant Acinetobacter baumannii (CRAB) isolated
      between 2000 and 2009. In this study, the antibiotic resistances, carbapenemase
      gene content and clonal relatedness of 194 single-patient CRAB clinical isolates
      collected randomly during 2015 from 11 tertiary hospitals located throughout
      Greece were investigated. Antimicrobial susceptibility was determined using
      commercial and dilution methods. PCR assays for carbapenemase genes were
      performed. Clonality was tested by a scheme based on two multiplex PCRs and
      single-locus blaOXA-51-like sequence-based typing. Furthermore, Pasteur's
      multilocus sequence typing (MLST) scheme and pulsed-field gel electrophoresis
      (PFGE) were applied to 31 selected representative isolates. The most active
      antibiotics were trimethoprim/sulfamethoxazole (SXT) (34.6% of isolates
      susceptible), minocycline (71.6%), colistin (72.7%) and tigecycline (MIC50/90
      values, 1/2 mg/L). The blaOXA-23-like gene was identified in 188 isolates
      (96.9%), blaOXA-23-like together with blaOXA-58-like in 3 isolates (1.5%), blaOXA
      58-like in 2 isolates (1.0%) and blaOXA-40-like in 1 isolate (0.5%). ISAba1 was
      found upstream of the blaOXA-23-like gene in all isolates. International clone
      (IC) 2 comprised 157 isolates (80.9%), IC1 comprised 36 isolates (18.6%) and ST78
      comprised 1 isolate (0.5%). All IC2 and IC1 isolates tested by MLST were ST2 and
      ST1, respectively. Seven PFGE types were detected. IC2 isolates were resistant to
      more antibiotics than IC1, except for SXT. This nationwide study showed that CRAB
      isolates in Greek hospitals currently produce almost uniformly the OXA-23
      carbapenemase and belong mainly to IC2 and, to a lesser extent, IC1. Of
      particular concern, colistin susceptibility is recently severely reduced.

PMID- 28427844
TI  - Cost effectiveness of influenza vaccination in patients with acute coronary
      syndrome in Korea.
AB  - BACKGROUND: Influenza can cause cardiovascular abnormalities by inappropriately
      activating the coagulation cascade. Therefore, influenza vaccination is important
      because it decreases the risk of hospitalization for and mortality associated
      with heart disease. In particular, it reduces the occurrence of major adverse
      cardiovascular events (MACEs) in acute coronary syndrome (ACS) patients. Our
      study aimed to estimate the disease burden of MACEs and its related direct and
      indirect costs in ACS patients. METHODS: We estimated the direct and indirect
      cost of MACEs in ACS patients using a probabilistic model and the Health
      Insurance Review and Assessment (HIRA)-National Patient Sample (NPS) database.
      The effect of the influenza vaccination on the rate of MACE in ACS patients was
      determined using a previous systematic review and meta-analysis. RESULTS: Our
      study included 682,258 ACS patients obtained from the 2013 NPS database.
      According to our model, influenza vaccination would prevent 16,514 MACE-related
      hospitalizations and 2764 premature deaths in Korea per year. The overall
      reduction in costs would be $86.2 million per year from a societal perspective.
      Based on the results of sensitivity analysis, most of the estimated values were
      in the dominant area. CONCLUSIONS: Our findings show that influenza vaccination
      in ACS patients is highly cost effective in terms of lowering the cost of
      hospitalization and premature death due to MACE. Therefore, influenza vaccination
      is recommended as a means of relieving the clinical and socioeconomic burdens
      associated with ACS.

PMID- 28427845
TI  - Development of a micro-neutralization assay for ebolaviruses using a replication
      competent vesicular stomatitis hybrid virus and a quantitative PCR readout.
AB  - Development of vaccines against highly pathogenic viruses that could also be used
      as agents of bioterrorism is both a public health issue and a national security
      priority. Methods that can quantify neutralizing antibodies will likely be
      crucial in demonstrating vaccine effectiveness, as most licensed viral vaccines
      are effective due to their capacity to elicit neutralizing antibodies. Assays to
      determine whether antibodies are neutralizing traditionally involve infectious
      virus, and the assay most commonly used is the plaque-reduction neutralization
      test (PRNT). However, when the virus is highly pathogenic, this assay must be
      done under the appropriate level of containment; for tier one select agents, such
      as Ebola virus (EBOV), it is performed under Biological Safety Level 4 (BSL-4)
      conditions. Developing high-throughput neutralization assays for these viruses
      that can be done in standard BSL-2 laboratories should facilitate vaccine
      development. Our approach is to use a replication-competent hybrid virus whose
      genome carries the envelope gene from the pathogenic virus on the genetic
      backbone of a non-pathogenic virus, such as vesicular stomatitis virus (VSV). We
      have generated hybrid VSVs carrying the envelope genes for several species of
      ebolavirus. The readout for infectivity is a one-step reverse transcriptase
      quantitative PCR (RT-qPCR), an approach that we have used for other viruses that
      allows robustness and adaptability to automation. Using this method, we have
      shown that neutralization can be assessed within 6-16h after infection.
      Importantly, the titers obtained in our assay with two characterized antibodies
      were in agreement with titers obtained in other assays. Finally, although in this
      paper we describe the VSV platform to quantify neutralizing antibodies to
      ebolaviruses, the platform should be directly applicable to any virus whose
      envelope is compatible with VSV biology.

PMID- 28427846
TI  - Vaccines are different: A systematic review of budget impact analyses of
      vaccines.
AB  - INTRODUCTION: Several countries require manufacturers to present a budget impact
      analysis (BIA), together with a cost-effectiveness analysis, to support national
      funding requests. However, guidelines for conducting BIA of vaccines are scarce.
      OBJECTIVES: To analyze the methodological approaches used in published budget
      impact analysis (BIA) of vaccines, discussing specific methodological issues
      related to vaccines. MATERIAL AND METHODS: This systematic review of the
      literature on BIA of vaccines was carried out in accordance with the Centre for
      Reviews and Dissemination - CRD guidelines. We searched multiple databases:
      MedLine, Embase, Biblioteca Virtual de Saude (BVS), Cochrane Library, DARE
      Database, NHS Economic Evaluation Database (NHS EED), HTA Database (via Centre
      for Reviews and Dissemination - CRD), and grey literature. Two researchers,
      working independently, selected the studies and extracted the data. The
      methodology quality of individual studies was assessed using the ISPOR 2012
      Budget Impact Analysis Good Practice II Task Force. A qualitative narrative
      synthesis was conducted. RESULTS: Twenty-two studies were reviewed. The most
      frequently evaluated vaccines were pneumococcal (41%), influenza (23%) and
      rotavirus (18%). The target population was stated in 21 studies (95%) and the
      perspective was clear in 20 (91%). Only 36% reported the calculations used to
      complete the BIA, 27% informed the total and disaggregated costs for each time
      period, and 9% showed the change in resource use for each time period. More than
      half of the studies (55%, n=12) reported less than 50% of the items recommended
      in the checklist. CONCLUSIONS: The production of BIA of vaccines has increased
      from 2009. The report of the methodological steps was unsatisfactory, making it
      difficult to assess the validity of the results presented. Vaccines specific
      issues should be discussed in international guidelines for BIA of vaccines, to
      improve the quality of the studies.

PMID- 28427847
TI  - Tetanus vaccines: WHO position paper, February 2017 - Recommendations.
AB  - This article presents the World Health Organization's (WHO) recommendations on
      the use of tetanus toxoid (TT) vaccines excerpted from the WHO position paper on
      tetanus vaccines - February 2017, published in the Weekly Epidemiological Record
      [1]. This position paper replaces the May 2006 WHO position paper on tetanus
      vaccines (Tetanus vaccines: WHO position paper, 2006). The position paper
      summarizes the recent developments in the field of tetanus prevention and
      provides revised guidance on the optimal timing of recommended tetanus vaccine
      booster doses. Footnotes to this paper provide a number of core references
      including references to grading tables that assess the quality of the scientific
      evidence, and to the evidence-to-recommendation table. In accordance with its
      mandate to provide guidance to Member States on health policy matters, WHO issues
      a series of regularly updated position papers on vaccines and combinations of
      vaccines against diseases that have an international public health impact. These
      papers are concerned primarily with the use of vaccines in large-scale
      immunization programmes; they summarize essential background information on
      diseases and vaccines, and conclude with WHO's current position on the use of
      vaccines in the global context. Recommendations on the use of TT-containing
      vaccines (TTCVs) were discussed by SAGE in October 2016; evidence presented at
      the meeting can be accessed at:
      http://www.who.int/immunization/sage/meetings/2016/october/presentations_backgrou
      d_docs/en/.

PMID- 28427848
TI  - Early outcomes and periprocedural complications of transarterial embolization of
      brain arteriovenous malformations with Onyx(r).
AB  - BACKGROUND: Brain arteriovenous malformation (BAVM) is a rare pathology diagnosed
      mostly in young adults. However, due to its hemorrhagic complications, it
      constitutes an important clinical problem. Treatment modalities available include
      endovascular, surgery and radiosurgery. The aim of the study was to assess the
      efficacy and safety of endovascular treatment of BAVM with Onyx(r) by reporting
      one-center experience. MATERIAL AND METHODS: Between 2006 and 2013, 54 patients
      with BAVM were embolized with Onyx. The group consisted of 24 males and 30
      females, aged 10 to 65 years (mean 42.6+/-15.4). Clinical manifestations of BAVMs
      were: hemorrhage in 27 (50.0%), headaches in 12 (22.2%), seizures in 7 (13.0%)
      and focal neurologic deficits in 2 (3.7%) patients. Six (11.1%) patients were
      asymptomatic. A majority of BAVMs were of II and III grade in Spetzler-Martin
      scale (19 and 22 cases respectively). RESULTS: A total number of 108 endovascular
      procedures were performed (mean 2.00+/-0.98 sessions/patient). Complete
      obliteration of malformation was achieved in 25 (46.3%) patients, mostly with
      grade II and III BAVMs. In 29 (53.7%) patients, embolization led to a decrease in
      size of BAVM that made it feasible for other treatment modality. Morbidity and
      mortality rates were 5.6% and 1.8% respectively. The rate of hemorrhagic
      complications was 9.3%. CONCLUSION: Embolization of BAVM with Onyx(r) is an
      effective and safe method of treatment. However, regarding type and consequences
      of complications, the technique needs further improvement.

PMID- 28427849
TI  - Sarcopenia, cachexia, and muscle performance in heart failure: Review update
      2016.
AB  - Cachexia in the context of heart failure (HF) has been termed cardiac cachexia,
      and represents a progressive involuntary weight loss. Cachexia is mainly the
      result of an imbalance in the homeostasis of muscle protein synthesis and
      degradation due to a lower activity of protein synthesis pathways and an over
      activation of protein degradation. In addition, muscle wasting leads to of
      impaired functional capacity, even after adjusting for clinical relevant
      variables in patients with HF. However, there is no sufficient therapeutic
      strategy in muscle wasting in HF patients and very few studies in animal models.
      Exercise training represents a promising intervention that can prevent or even
      reverse the process of muscle wasting, and worsening the muscle function and
      performance in HF with muscle wasting and cachexia. The pathological mechanisms
      and effective therapeutic approach of cardiac cachexia remain uncertain, because
      of the difficulty to establish animal cardiac cachexia models, thus novel animal
      models are warranted. Furthermore, the use of improved animal models will lead to
      a better understanding of the pathways that modulate muscle wasting and
      therapeutics of muscle wasting of cardiac cachexia.

PMID- 28427850
TI  - Five-year changes in cardiac structure and function in patients with rheumatoid
      arthritis compared with the general population.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) have increased risk of heart
      failure with preserved ejection fraction. The development and progression of left
      ventricular dysfunction before onset of clinical heart failure are unknown. The
      objective of this study was to evaluate longitudinal changes in cardiac structure
      and function of patients with RA compared with persons in the general population.
      METHODS: A prospective longitudinal study of a population-based cohort of 160
      patients with RA and a population-based cohort of 1391 persons without RA (non-RA
      cohort) was performed. Each participant underwent 2-dimensional, pulsed-wave
      tissue Doppler echocardiography at baseline and after 4 to 5years of follow-up.
      Age- and sex-adjusted linear regression models were used to test for differences
      between the RA and non-RA cohorts in annualized rates of change for
      echocardiographic parameters. RESULTS: Mitral A velocity increased more rapidly
      among the patients with RA than the non-RA cohort (age- and sex-adjusted
      parameter estimate, 0.030; P<0.001). Correspondingly, the mean mitral inflow E/A
      ratio decreased faster in the RA cohort than the non-RA cohort (adjusted
      parameter estimate, -0.096; P<0.001). The left atrial volume index increased at a
      higher rate in the RA cohort than the non-RA cohort (adjusted parameter estimate,
      0.150; P<0.001). CONCLUSIONS: This pattern of echocardiographic findings confirms
      previous cross-sectional studies and indicates that subclinical changes in
      diastolic function occur more rapidly over 5years in RA patients than in the
      general population. Further research into the mechanisms of myocardial disease in
      these patients and the relationship with disease activity and treatment is
      warranted.

PMID- 28427851
TI  - Circulating ceruloplasmin, ceruloplasmin-associated genes, and the incidence of
      atrial fibrillation in the atherosclerosis risk in communities study.
AB  - BACKGROUND: Ceruloplasmin (CP) may promote structural changes in the atrium
      making it more arrhythmogenic. We assessed the associations between CP, CP
      associated genetic variants, and incident atrial fibrillation (AF) in the
      Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: We studied
      10,059 men and women without prevalent AF aged 53 to 75years in 1996-1998 and
      followed through 2012. Circulating CP was measured in stored blood samples
      obtained in 1996-1998. Polymorphisms rs11708215 and rs13072552, previously
      associated with CP concentrations, were measured in 10,059 and 8829 participants
      respectively. AF was ascertained from study electrocardiograms, hospital
      discharge codes, and death certificates. Multivariable Cox models were run to
      study the association between circulating CP, CP-associated polymorphisms, and
      the incidence of AF. Over 10.5years of mean follow-up, 1357 cases of AF were
      identified. After adjusting for traditional risk factors and biomarkers, higher
      levels of circulating CP were associated with incident AF (hazard ratio [HR]
      1.33, 95% confidence interval [CI] 1.11, 1.61 comparing top to bottom quartiles).
      Both rs11708215 and rs13072552 were significantly associated with CP levels.
      Presence of the CP-increasing alleles in rs11708215 and rs13072552, however, were
      significantly associated with lower risk of AF in whites (HR 0.84, 95%CI 0.76,
      0.94, p=0.002 and HR 0.83; 95%CI 0.69, 0.99, p=0.043 respectively per CP
      increasing allele in the final adjusted model) but not in African Americans.
      CONCLUSIONS: Even though higher CP concentrations were associated with increased
      AF risk, genetic variants associated with higher CP decreased the risk of AF in
      whites. Our results suggest that circulating CP levels may not be causally
      related to risk of incident AF.

PMID- 28427852
TI  - Circumferential pulmonary vein isolation with second-generation multipolar
      catheter in patients with paroxysmal or persistent atrial fibrillation:
      Procedural and one-year follow-up results.
AB  - BACKGROUND: There is a lack of procedural and follow-up data on pulmonary vein
      isolation (PVI) with the second-generation pulmonary vein ablation catheter(r)
      (PVAC Gold) in patients with atrial fibrillation (AF). This study provides data
      on PVI procedures and 1-year follow-up results with PVAC Gold in patients with AF
      treated in clinical practice. METHODS AND RESULTS: Three hundred and eighty four
      patients with documented symptomatic paroxysmal (n=198) or persistent (n=186) AF
      were included in a non-randomized prospectively designed database. Patients were
      enrolled consecutively at 2 high-volume centers. Procedural as well as 1year
      follow-up data were systematically analyzed. Average procedure times+/-standard
      deviations were 94+/-23min and 97+/-23min, respectively, in patients with
      paroxysmal and persistent AF. Average fluoroscopy times were 14.7+/-5.4min and
      15.2+/-5.6min and total application times 18.1+/-5.0min and 18.8+/-5.2min,
      respectively, in the 2 patient cohorts. At 12months, 70.7% (70/99) and 61.9%
      (70/113) of patients with paroxysmal and persistent AF, respectively, were free
      from AF. Four early complications occurred. In the group with persistent AF, 1
      posterior cerebral infarction occurred 2days after the procedure during
      initiation of anticoagulation. There was no phrenic nerve palsy or esophageal
      injury associated with the procedures. No thromboembolic events were recorded
      during follow-up. CONCLUSIONS: In patients with paroxysmal or persistent AF,
      second generation multi-electrode-phased radiofrequency ablation delivers
      favorable mid-term PVI success rates with few procedure-related or follow-up
      complications.

PMID- 28427853
TI  - Treatment of critical hypercalcemia using pamidronate in acute megakaryoblastic
      leukemia in an 18-month-old girl.

PMID- 28427854
TI  - Geospatial analysis of unmet pediatric surgical need in Uganda.
AB  - BACKGROUND: In low- and middle-income countries (LMICs), an estimated 85% of
      children do not have access to surgical care. The objective of the current study
      was to determine the geographic distribution of surgical conditions among
      children throughout Uganda. METHODS: Using the Surgeons OverSeas Assessment of
      Surgical Need (SOSAS) survey, we enumerated 2176 children in 2315 households
      throughout Uganda. At the district level, we determined the spatial
      autocorrelation of surgical need with geographic access to surgical centers
      variable. FINDINGS: The highest average distance to a surgical center was found
      in the northern region at 14.97km (95% CI: 11.29km-16.89km). Younger children
      less than five years old had a higher prevalence of unmet surgical need in all
      four regions than their older counterparts. The spatial regression model showed
      that distance to surgical center and care availability were the main spatial
      predictors of unmet surgical need. INTERPRETATION: We found differences in unmet
      surgical need by region and age group of the children, which could serve as
      priority areas for focused interventions to alleviate the burden. Future studies
      could be conducted in the northern regions to develop targeted interventions
      aimed at increasing pediatric surgical care in the areas of most need. LEVEL OF
      EVIDENCE: Level III.

PMID- 28427855
TI  - Outcome of medical management of intraabdominal abscesses in children with Crohn
      disease.
AB  - INTRODUCTION: Crohn disease (CD) is a chronic inflammatory condition of the
      gastrointestinal tract that is complicated by fistulas, strictures, and
      intraabdominal abscesses (IAA) in 10%-30% of patients. To avoid surgical
      resection of the bowel, medical therapy with antibiotics (Ab) with or without
      percutaneous drainage (PD) is first undertaken. Our objectives are to examine the
      outcome of IAA in CD patients treated with antibiotics alone vs antibiotics and
      PD, and to identify risk factors for medical therapy failure. METHODS: Charts for
      patient with CD who were diagnosed between 2004 and 2016 at the Women and
      Children's Hospital of Buffalo were retrospectively reviewed. We compared the two
      modalities of medical therapy (Ab + PD vs Ab alone) in terms of abscess
      resolution and the need for surgical intervention. RESULTS: Twenty-nine patients,
      ages ranging from 12 to 18years, mean 15.5+/-2.5, 48% Male with IAA were
      identified. Overall, 69% of abscesses failed medical therapy including 87% of the
      drained abscesses and 50% of nondrained abscesses, p=0.04. The abscesses that
      failed medical therapy were more likely to have been drained (P=0.03) as they
      were larger in size (P = 0.03), patients were more likely to have a known CD on
      immunosuppression (P=0.016), and more likely to have an associated upper GI
      disease (P=0.002), when compared to those that were successful with medical
      therapy alone. CONCLUSION: Our results show that the majority of our patients
      required surgical intervention for abscess treatment and resolution of associated
      findings despite drainage. Risk factors include big drainable abscesses,
      developing IAA while on immunosuppression, and a more extensive disease with
      associated fistulae and strictures. Small undrainable abscesses are likely to
      resolve with antibiotics alone, therefore early detection and treatment are
      essential. TYPE OF STUDY: Level 2, retrospective study.

PMID- 28427856
TI  - Frizzled 3 acts upstream of Alcam during embryonic eye development.
AB  - Formation of a functional eye during vertebrate embryogenesis requires different
      processes such as cell differentiation, cell migration, cell-cell interactions as
      well as intracellular signalling processes. It was previously shown that the non
      canonical Wnt receptor Frizzled 3 (Fzd3) is required for proper eye formation,
      however, the underlying mechanism is poorly understood. Here we demonstrate that
      loss of Fzd3 induces severe malformations of the developing eye and that this
      defect is phenocopied by loss of the activated leukocyte cell adhesion molecule
      (Alcam). Promoter analysis revealed the presence of a Fzd3 responsive element
      within the alcam promoter, which is responsible for alcam expression during
      anterior neural development. In-depth analysis identified the jun N-terminal
      protein kinase 1 (JNK1) and the transcription factor paired box 2 (Pax2) to be
      important for the activation of alcam expression. Altogether our study reveals
      that alcam is activated through non-canonical Wnt signalling during embryonic eye
      development in Xenopus laevis and shows that this pathway plays a similar role in
      different tissues.

PMID- 28427857
TI  - Vitrified-warmed single-embryo transfers may be associated with increased
      maternal complications compared with fresh single-embryo transfers.
AB  - Cryopreservation of embryos allows single-embryo transfer and storage of
      supernumerary embryos, maximizing cumulative pregnancy rates. The purpose of this
      retrospective cohort study was to compare pregnancy outcome in singletons born
      after fresh or vitrified-warmed single blastocyst transfer (SBT). Singleton live
      births resulting from SBT of fresh or vitrified-warmed embryos were compared.
      Primary outcomes were perinatal outcomes including small for gestational age
      (SGA), low birthweight, preterm deliveries (PTD), large for gestational age (LGA)
      and congenital malformations. Maternal complications included pre-eclampsia,
      placenta previa, placental abruption, gestational diabetes mellitus (GDM) and
      chorioamnionitis. Adjustment for confounding factors was performed. Of 1886 fresh
      SBTs and 1200 vitrified-warmed SBTs during the study period, vitrified-warmed
      SBTs compared with fresh SBTs resulted in significantly lower clinical pregnancy
      rate (P < 0.0001). Live birth and miscarriage rates calculated only for pregnancy
      with known outcome revealed lower live birth rates and higher miscarriage rates
      for the vitrified-warmed group. Perinatal complications were calculated for
      clinical pregnancies with known outcomes (12.9% catchment failure was excluded
      from analysis). The vitrified-warmed group showed a trend toward higher rates of
      pre-eclampsia, GDM, Caesarean delivery and LGA neonates. Rates of PTD and SGA
      were comparable. In conclusion, vitrified-warmed SBT might be associated with
      increased feto-maternal complications.

PMID- 28427858
TI  - Mice with conditional NeuroD1 knockout display reduced aberrant hippocampal
      neurogenesis but no change in epileptic seizures.
AB  - Adult neurogenesis is significantly increased in the hippocampus of rodent models
      of temporal lobe epilepsy (TLE). These adult-generated neurons have recently been
      shown to play a contributing role in the development of spontaneous recurrent
      seizures (SRS). In order to eventually target pro-epileptic adult neurogenesis in
      the clinical setting, it will be important to identify molecular players involved
      in the control of aberrant neurogenesis after seizures. Here, we focused on
      NeuroD1 (ND1), a member of the bHLH family of transcription factors previously
      shown to play an essential role in the differentiation and maturation of adult
      generated neurons in the hippocampus. Wild-type mice treated with pilocarpine to
      induce status epilepticus (SE) showed a significant up-regulation of NeuroD1+
      immature neuroblasts located in both the granule cell layer (GCL), and
      ectopically localized to the hilar region of the hippocampus. As expected,
      conditional knockout (cKO) of NeuroD1 in Nestin-expressing stem/progenitors and
      their progeny led to a reduction in the number of NeuroD1+ adult-generated
      neurons after pilocarpine treatment compared to WT littermates. Surprisingly,
      there was no change in SRS in NeuroD1 cKO mice, suggesting that NeuroD1 cKO fails
      to reduce aberrant neurogenesis below the threshold needed to impact SRS.
      Consistent with this conclusion, the total number of adult-generated neurons in
      the pilocarpine model, especially the total number of Prox1+ hilar ectopic
      granule cells were unchanged after NeuroD1 cKO, suggesting strategies to reduce
      SRS will need to achieve a greater removal of aberrant adult-generated neurons.

PMID- 28427860
TI  - Differential mTOR pathway profiles in bladder cancer cell line subtypes to
      predict sensitivity to mTOR inhibition.
AB  - BACKGROUND: Molecular classification of bladder cancer has been increasingly
      proposed as a potential tool to predict clinical outcomes and responses to
      chemotherapy. Here we focused on mechanistic target of rapamycin (mTOR)
      inhibition as a chemotherapeutic strategy and characterized the expression
      profile of mTOR signaling targets in representative bladder cancer cell lines
      from basal, luminal, and either basal/luminal ("non-type") molecular subtypes.
      MATERIALS AND METHODS: Protein and mRNA expression of mTOR signaling components
      from representative luminal (RT4 and RT112), basal (SCaBER and 5637), and nontype
      (T24 and J82) bladder cancer cell line subtypes were determined by Western blot
      and database mining analysis of the Cancer Cell Line Encyclopedia. Cell viability
      following treatment with either, Torin-2 or KU-0063794, 2 dual mTOR complex 1/2
      inhibitors, was determined by MTT assay. Immunoblot analysis of cells treated
      with Torin-2 or KU-0063794 was performed to determine the effects of mTOR
      inhibition on expression and phosphorylation status of mTOR signaling components,
      Akt, 4E-BP1, and ribosomal protein S6. RESULTS: Molecular subtypes of bladder
      cancer cell lines each exhibited a distinct pattern of expression of mTOR
      associated genes and baseline phosphorylation level of Akt and 4E-BP1. Cells with
      low levels of Akt Ser-473 phosphorylation were more resistant to the cytotoxic
      effects of mTOR inhibition with Torin-2, but not KU-0063794. Exposure to Torin-2
      and KU-0063794 both potently and rapidly inhibited phosphorylation of Akt Ser-473
      and Thr-308, and 4E-BP1 T37/46 in cell lines that included basal and nontype
      subtypes. CONCLUSIONS: Differential gene expression and protein activity
      associated with mTOR signaling is observed among bladder cancer cell lines
      stratified into basal, luminal, and nontype subtypes. Urothelial carcinomas
      characterized by high baseline Akt Ser-473 phosphorylation may be best suited for
      targeted mTOR therapies.

PMID- 28427859
TI  - The role of c-Met in prognosis and clinicopathology of renal cell carcinoma:
      Results from a single-centre study and systematic review.
AB  - BACKGROUND AND OBJECTIVES: The c-Met proto-oncogene pathway plays an important
      role in the progression of various cancers. However, the effect of the c-Met
      pathway on renal cell carcinoma (RCC) remains controversial. We decided to
      clarify the role of c-Met in prognosis and clinicopathology of RCC. METHODS: A
      total of 10 pairs of tumour and adjacent tissues were obtained from patients with
      primary RCC between 2013 and 2014 and tissue microarrays to assess c-Met
      expression in tumour tissues from 90 patients with RCC by Western blot and
      immunohistochemical staining. We also presented a meta-analysis to explore the
      correlation between c-Met and pathological grade and stage of RCC. The two-tailed
      Pearson's chi2 and Fischer exact tests were used to compare categorical
      variables. Multivariate analysis was performed using the multivariate Cox
      proportional hazards model. RESULTS: C-Met protein levels were increased in 8 of
      10 RCC tissue samples compared with their adjacent normal tissue and c-Met
      expression levels were positively associated with a high nuclear grade (P =
      0.008) and pT stage (P = 0.002). Multivariate analysis showed that a high
      expression of c-Met was an independent predictor of disease-specific survival (P
      = 0.017). A meta-analysis found that increased c-Met expression in RCC tissues
      was closely correlated with high tumour grade (P<0.001) and high pT stage (P =
      0.001). Most importantly, c-Met expression was significantly correlated with
      disease-specific survival (P<0.001). CONCLUSIONS: Because c-Met is strongly
      associated with pathological grade, stage and disease-specific survival, c-Met
      levels may have potential to predict patient prognosis and to guide clinical
      diagnosis and treatment.

PMID- 28427861
TI  - Divergent Function of Programmed Death-Ligand 1 in Donor Tissue versus Recipient
      Immune System in a Murine Model of Bronchiolitis Obliterans.
AB  - Costimulatory molecules, such as the programmed death ligand (PD-L1), might exert
      differential effects on T-cell function, depending on the clinical setting and/or
      immunological environment. Given the impact of T cells on bronchiolitis
      obliterans (BO) in lung transplantation, we used an established tracheal
      transplant model inducing BO-like lesions to investigate the impact of PD-L1 on
      alloimmune responses and histopathological outcome in BO. In contrast to other
      transplant models in which PD-L1 generally shows protective functions, we
      demonstrated that PD-L1 has divergent effects depending on its location in donor
      versus recipient tissue. Although PD-L1 deficiency in donor tissue worsened
      histopathological outcome, and increased systemic inflammatory response,
      recipient PD-L1 deficiency induced opposite effects. Mechanistic studies revealed
      PD-L1-deficient recipients were hyporesponsive toward alloantigen, despite
      increased numbers of CD8+ effector T cells. The function of PD-L1 on T cells
      after unspecific stimulation was dependent on both cell type and strength of
      stimulation. This novel function of recipient PD-L1 may result from the high
      degree of T-cell activation within the highly immunogenic milieu of the
      transplanted tissue. In this model, both decreased T-cell alloimmune responses
      and the reduction of BO in PD-L1-deficient recipients suggest a potential
      therapeutic role of selectively blocking PD-L1 in the recipient. Further
      investigation is warranted to determine the impact of this finding embedded in
      the complex pathophysiological context of BO.

PMID- 28427862
TI  - Molecular evolution of pancreatic ribonuclease gene (RNase1) in Rodentia.

PMID- 28427864
TI  - Medically-managed Patients With NonST-segment Elevation Acute Coronary Syndromes:
      An Ill-defined Entity.

PMID- 28427865
TI  - Dynamics and energetics of cyanobacterial photosystem I:ferredoxin complexes in
      different redox states.
AB  - Fast turnover of ferredoxin/Fd reduction by photosystem-I/PSI requires that it
      dissociates rapidly after it has been reduced by PSI:Fd intracomplex electron
      transfer. The rate constants of Fd dissociation from PSI have been determined by
      flash-absorption spectroscopy with different combinations of cyanobacterial PSIs
      and Fds, and different redox states of Fd and of the terminal PSI acceptor
      (FAFB). Newly obtained values were derived firstly from the fact that the
      dissociation constant between PSI and redox-inactive gallium-substituted Fd
      increases upon (FAFB) reduction and secondly from the characterization and
      elucidation of a kinetic phase following intracomplex Fd reduction to binding of
      oxidized Fd to PSI, a process which is rate-limited by the foregoing dissociation
      of reduced Fd from PSI. By reference to the complex with oxidized partners,
      dissociation rate constants were found to increase moderately with (FAFB) single
      reduction and by about one order of magnitude after electron transfer from (FAFB)
      to Fd, therefore favoring turnover of Fd reduction by PSI. With
      Thermosynechococcus elongatus partners, values of 270, 730 and >10000s-1 were
      thus determined for (FAFB)Fdoxidized, (FAFB)-Fdoxidized and (FAFB)Fdreduced,
      respectively. Moreover, assuming a conservative upper limit for the association
      rate constant between reduced Fd and PSI, a significant negative shift of the Fd
      midpoint potential upon binding to PSI has been calculated (< -60mV for
      Thermosynechococcus elongatus). From the present state of knowledge, the question
      is still open whether this redox shift is compatible with a large (>10)
      equilibrium constant for intracomplex reduction of Fd from (FAFB)-.

PMID- 28427866
TI  - Effect of amyloid-Beta (25-35) in hyperglycemic and hyperinsulinemic rats,
      effects on phosphorylation and O-GlcNAcylation of tau protein.
AB  - Aggregation of the amyloid beta (Abeta) peptide and hyperphosphorylation of tau
      protein, which are markers of Alzheimer's disease (AD), have been reported also
      in diabetes mellitus (DM). One regulator of tau phosphorylation is O
      GlcNAcylation, whereas for hyperphosphorylation it could be GSK3beta, which is
      activated in hyperglycemic conditions. With this in mind, both O-GlcNAcylation
      and phosphorylation of tau protein were evaluated in the brain of rats with
      streptozotocin (STZ)-induced hyperglycemia and hyperinsulinemia and treated with
      the Abeta25-35 peptide in the hippocampal region CA1. Weight, glycated
      hemoglobin, glucose, and insulin were determined. Male Wistar rats were divided
      in groups (N=20): a) control, b) treated only with the Abeta25-35 peptide, c)
      treated with Abeta25-35 and STZ, and d) treated only with STZ. Results showed
      statistically significant differences in the mean weight, glucose levels, insulin
      concentration, and HbA1c percentage, between C- and D-treated groups and not STZ
      treated A and B (P<0.05). Interestingly, our results showed diminution of O
      GlcNAcylation and increase in P-tau-Ser-396 in the hippocampal area of the
      Abeta25-35- and STZ-treated groups; moreover, enhanced expression of GSK3beta was
      observed in this last group. Our results suggest that hyperinsulinemia-Abeta25-35
      hyperglycemia is relevant for the down regulation of O-GlcNAcylation and up
      regulation of the glycogen synthase kinase-3 beta (GSK3beta), favoring Abeta25-35
      induced neurotoxicity in the brain of rats.

PMID- 28427867
TI  - Outcomes from anomalous origin of the left coronary artery from the pulmonary
      artery repair: Long-term complications in relation to residual myocardial
      abnormalities.
AB  - BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary
      artery (ALCAPA) is a rare congenital coronary artery irregularity. This study
      aimed to clarify the long-term postoperative outcomes in ALCAPA patients, and to
      compare the infantile and adult types. METHODS: We retrospectively analyzed the
      clinical data from 33 patients with ALCAPA who underwent surgical repairs after
      1980. The patients were grouped based on whether presentation occurred before
      (infantile type: n=14) or after (adult type: n=19) 1 year of age. RESULTS: The
      mean follow-up duration was 16 years. Preoperatively, the infantile type had
      greater impairment of the left ventricle ejection fraction (LVEF) (45+/-15%)
      compared with the adult type (59+/-10%) (p<0.01). Coronary revascularization
      significantly improved the postoperative LVEF (67+/-5%) (p<0.01) in the patients
      with the infantile type. The postoperative LVEF did not change in the adult type.
      The mitral regurgitation (MR) severity improved postoperatively, but the between
      group difference was not significant. Postoperatively, none of the patients with
      the infantile type and 37% of the patients with the adult type had left
      ventricular asynergy (p=0.01), and both groups showed postoperative perfusion
      defects (79% vs 95%, p=0.29). Compared with the infantile type, the adult type
      had a significant prognostic value for composite cardiovascular events that
      comprised cardiac death, arrhythmias, MR deterioration, and hospitalization as a
      consequence of heart failure (p=0.04). CONCLUSIONS: Most patients showed
      favorable clinical outcomes postoperatively, but myocardial damage remained long
      after surgery and cardiovascular events occurred postoperatively. Hence,
      meticulous long-term follow-up is warranted.

PMID- 28427863
TI  - ROS in Cancer: The Burning Question.
AB  - An unanswered question in human health is whether antioxidation prevents or
      promotes cancer. Antioxidation has historically been viewed as chemopreventive,
      but emerging evidence suggests that antioxidants may be supportive of neoplasia.
      We posit this contention to be rooted in the fact that ROS do not operate as one
      single biochemical entity, but as diverse secondary messengers in cancer cells.
      This cautions against therapeutic strategies to increase ROS at a global level.
      To leverage redox alterations towards the development of effective therapies
      necessitates the application of biophysical and biochemical approaches to define
      redox dynamics and to functionally elucidate specific oxidative modifications in
      cancer versus normal cells. An improved understanding of the sophisticated
      workings of redox biology is imperative to defeating cancer.

PMID- 28427868
TI  - Potential palliative care quality indicators in heart disease patients: A review
      of the literature.
AB  - In spite of the increasing interest in palliative care for heart disease, data on
      the detailed methods of palliative care and its efficacy specifically in heart
      disease are still lacking. A structured PubMed literature review revealed no
      quality indicators of palliative care in heart disease. Therefore, we performed a
      narrative overview of the potential quality indicators in heart disease by
      reviewing previous literature concerning quality indicators in cancer patients.
      We summarize seven potential categories of quality indicators in heart disease:
      (1) presence and availability of a palliative care unit, palliative care team,
      and outpatient palliative care; (2) human resources such as number of skilled
      staff; (3) infrastructure; (4) presence and frequency of documentation or family
      survey; (5) patient-reported outcome measure (PROM) data and disease-specific
      patient quality of life such as The Kansas City Cardiomyopathy Questionnaire
      (KCCQ); (6) questionnaires and interviews about the quality of palliative care
      after death, including bereaved family surveys; and (7) admission-related
      outcomes such as place of death and intensive care unit length of stay. Although
      detailed measurements of palliative care quality have not been validated in heart
      disease, many indicators developed in cancer patients might also be applicable to
      heart disease. This new categorization might be useful to determine quality
      indicators in heart disease patients.

PMID- 28427869
TI  - Ischemic preconditioning with a ketogenic diet improves brain ischemic tolerance
      through increased extracellular adenosine levels and hypoxia-inducible factors.
AB  - Ischemic tolerance reduces brain damage and neurological dysfunction after brain
      ischemia. A ketogenic diet (KD) has disease-modifying effects in several
      neurodegenerative disorders. In this study, we fed mice with a KD for three weeks
      and performed reversible middle cerebral artery occlusion (MCAO) in the animals.
      KD-fed mice had a significantly reduced infarct volume, increased regional
      cerebral blood flow (rCBF) and extracellular adenosine levels in both the
      ischemic and the reperfusion phases. In vitro and in vivo experiments revealed
      that the KD-induced neuroprotection was mediated through the adenosine A1
      receptor. The KD increased Akt and ERK1/2 phosphorylation via A1R activation.
      Besides, the KD also upregulated robustly HIF-1alpha/HIF-2alpha and HIF regulated
      genes, such as VEGF and EPO. A three-week preconditioning period with a KD
      improved ischemic tolerance in mice with MCAO. The underlying mechanisms might
      include elevated extracellular adenosine levels, and increased Akt and ERK1/2
      phosphorylation via A1 adenosine receptor activation, together with upregulated
      HIFs and HIF-regulated genes.

PMID- 28427870
TI  - All-Endoscopic Brachial Plexus Complete Neurolysis for Idiopathic Neurogenic
      Thoracic Outlet Syndrome: A Prospective Case Series.
AB  - PURPOSE: To describe an all-endoscopic technique for infra- and supraclavicular
      brachial plexus (BP) neurolysis and to assess its functional outcomes for
      patients suffering from nonspecific neurogenic thoracic outlet syndrome (NTOS).
      METHODS: Between January 2010 and January 2013, 36 patients presenting an
      idiopathic nonspecific NTOS benefited from an endoscopic decompression in our
      institution. The inclusion criteria were a typical clinical NTOS and failure of a
      6-month well-conducted nonsurgical treatment. Preoperative findings about other
      shoulder conditions and complementary procedures were exclusion criteria.
      Interscalene, costoclavicular, and retropectoralis minor spaces were released
      endoscopically. The primary endpoint was the Disability of the Arm, Shoulder and
      Hand (DASH) score improvement 6 months after the surgery. Postoperative criteria
      such as pain relief, paresthesia, upper limb weakness, and provocative tests were
      also assessed. RESULTS: Of 36 patients, 10 were excluded and 5 were lost during
      follow-up. The data of the 21 remaining patients were analyzed after 6 months.
      Pre- and postoperative mean DASH scores were, respectively, 70 (range 36-98) and
      34 (range 2-91). The average improvement was 36 (range -20 to 80), with P =
      .0002. Pain and paresthesia were relieved in 80% to 90% of the cases. No
      complication was reported. CONCLUSIONS: Although requiring arthroscopic skills
      and expert knowledge of the anatomy, our technique seems to be safe and
      reproducible, and it provides significant functional improvements in the selected
      patients with nonspecific NTOS, with an average postoperative DASH score
      improvement of 36%. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 28427871
TI  - Arthroscopic-Assisted Coracoclavicular Ligament Reconstruction for Acute
      Acromioclavicular Dislocation Using 2 Clavicular and 1 Coracoid Cortical Fixation
      Buttons With Suture Tapes.
AB  - PURPOSE: To introduce an arthroscopically assisted coracoclavicular (CC) fixation
      technique using a cortical fixation button device and to evaluate the clinical
      and radiologic outcomes in patients with acute acromioclavicular (AC) dislocation
      who were treated with the technique. METHODS: Twenty-one consecutive patients
      with grade III and V acute AC dislocation who underwent arthroscopically assisted
      CC ligament reconstruction using a cortical fixation button device were
      prospectively enrolled. Our fixation technique involved using a cortical fixation
      button device consisting of 1 coracoid button and 2 clavicular buttons connected
      with 2 suture tapes to reconstruct the conoid and trapezoid ligaments,
      respectively. Clinical outcomes were evaluated and CC distance and horizontal
      displacement of the AC joint were measured. RESULTS: The mean follow-up period
      was 27.2 months (range, 24-32 months). The average CC distance of the injured
      shoulder was 17.2 +/- 5.2 mm preoperatively, which represented an increase of
      103% +/- 42% compared with the uninjured shoulder. The CC distance was
      significantly reduced to 8.5 +/- 1.5 mm after surgery (P < .001). At the final
      follow-up, the CC distance was maintained in 20 patients (95%) without loss of
      reduction. No significant radiologic difference was found in horizontal
      displacement of the AC joint immediately after the operation and at the final
      follow-up (P = .422). The average American Shoulder and Elbow Surgeons and
      Constant scores were 95.7 +/- 3.6 and 95.4 +/- 3.4, respectively. There were 3
      complications, including 1 reduction loss, 1 coracoid process fracture, and 1 CC
      interval ossification. CONCLUSIONS: Satisfactory clinical and radiologic outcomes
      were obtained simultaneously by arthroscopically assisted CC reconstruction using
      cortical fixation buttons. This reconstruction technique provided sufficient
      stability of the AC joint by using 2 clavicular holes to reconstruct the conoid
      and trapezoid ligaments separately. Therefore, arthroscopically assisted CC
      ligament reconstruction using a cortical fixation button device for management of
      acute AC dislocation is considered a viable treatment option for restoring
      stability to the AC joint. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 28427872
TI  - Abduction Brace Versus Antirotation Sling After Arthroscopic Cuff Repair: The
      Effects on Pain and Function.
AB  - PURPOSE: To study the effects on pain as the main outcome parameter and on
      function and cuff integrity as the secondary outcome parameters after
      arthroscopic rotator cuff repair in the short term comparing the abduction brace
      with an antirotation sling for postoperative shoulder immobilization. METHODS:
      Eligible patients were between the ages of 18 and 75 years who were diagnosed
      with a traumatic or degenerative tear of the supraspinatus and/or infraspinatus
      tendon, confirmed by magnetic resonance imaging, for which an arthroscopic
      footprint repair was indicated and performed. Patients were randomly allocated to
      the antirotation sling or abduction brace group. Postoperative pain and use of
      analgesics were accurately registered up to 3 months after surgery using a
      patient diary. Follow-up examinations including the Constant-Murley score,
      Western Ontario Rotator Cuff index, and glenohumeral range of motion were
      scheduled 6 weeks, 3 and 6 months, and 1 year after surgery. RESULTS: The average
      level of pain measured directly postoperation up to 1 year after surgery was not
      significant different between groups. Postoperatively, function scores and
      glenohumeral range of motion improved significantly for both groups; however, no
      differences were observed between groups. No retears were observed on
      ultrasonograph 3 months after surgery. CONCLUSIONS: In the short term, the level
      of pain, function, and quality of life were not significantly different between
      the use of an abduction brace and that of an antirotation sling after
      arthroscopic rotator cuff repair. Based on these findings, the abduction brace
      used in this study does not seem to be the solution for decreasing the pain
      experienced in the first postoperative weeks after arthroscopic rotator cuff
      repair, and both are recommendable. LEVEL OF EVIDENCE: Level I, randomized
      controlled trial.

PMID- 28427873
TI  - Risk Factors for Hospital Admission After Anterior Cruciate Ligament
      Reconstruction.
AB  - PURPOSE: To determine patient and surgical risk factors for admission after
      anterior cruciate ligament reconstruction (ACLR) using the American College of
      Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.
      METHODS: All instances of ACLR from 2005 to 2014 from the ACS NSQIP prospective
      database were analyzed. Both univariate analysis and binary logistic regression
      were performed to determine which patient demographics and medical comorbidities
      were associated with admission after surgery. RESULTS: Of the 9,146 patients
      undergoing ACLR, 1,197 (13.1%) required admission. Univariate analysis found that
      the following variables were associated with the need for admission: decreased
      age, Hispanic ethnicity, higher American Society of Anesthesiologists class,
      higher Charlson Comorbidity Index, use of an epidural anesthesia, longer
      operative times, prior operation within 30 days, dyspnea, smoking, diabetes,
      chronic obstructive pulmonary disease, previous cardiac surgery, hypertension,
      previous revascularization procedure, and a known bleeding disorder. Independent
      predictors of admission on multivariate analysis included Hispanic ethnicity
      (odds ratio [OR] 8.9), use of epidural anesthesia (OR 6.3), known bleeding
      disorder (OR 4.02), increased body mass index (OR 1.03), longer operation time
      (OR 1.012), and younger age (OR 1.008). CONCLUSIONS: Our study identifies
      Hispanic ethnicity, use of epidural anesthesia, and history of bleeding disorder
      as major independent risk factors for admission after ACLR. LEVEL OF EVIDENCE:
      Level III, retrospective comparative study.

PMID- 28427874
TI  - Factors That Increase the Risk of Infection After Elbow Arthroscopy: Analysis of
      Patient Demographics, Medical Comorbidities, and Steroid Injections in 2,704
      Medicare Patients.
AB  - PURPOSE: To use a national database to determine (1) the incidence of joint
      infection after elbow arthroscopy, (2) identify independent patient-related risk
      factors for infection, and (3) determine the influence of concomitant intra
      articular corticosteroid injection on infection risk. METHODS: The 100% Medicare
      Standard Analytic Files were queried to identify patients who underwent elbow
      arthroscopy from 2005 to 2012. Postoperative elbow infections occurring within 6
      months of surgery were identified using both International Classification of
      Diseases, 9th Revision codes for postoperative infection and Current Procedural
      Terminology codes for the surgical treatment of a postoperative infection.
      Patients were excluded if their initial arthroscopic procedure was performed for
      infection. A multivariate binomial logistic regression analysis was then used to
      evaluate patient-related risk factors for postoperative infection. RESULTS: Of
      the 2,704 elbow arthroscopy cases identified, 42 (1.55%) developed a
      postoperative infection. The annual incidence of infections did not increase
      significantly over the course of the study (P = .374). A number of patient
      demographics and medical comorbidities significantly increased the risk of
      infection. The most notable factors included age >= 65 years (odds ratio [OR]
      2.38, P = .006), body mass index > 40 (OR 1.97, P = .024), tobacco usage (OR
      1.80, P = .046), alcohol usage (OR 4.01, P < .001), diabetes mellitus (OR 2.10, P
      = .015), inflammatory arthritis (OR 2.81, P < .001), hypercoagulable disorder (OR
      2.51, P = .015), and intra-articular corticosteroid injection at the time of
      arthroscopy (OR 2.79, P = .006). CONCLUSIONS: The annual number of elbow
      arthroscopies performed in the United States has increased steadily; however, the
      postoperative infection rate remained consistently low at 1.55%. There are a
      number of patient-specific risk factors that increase this risk with OR ranging
      from 1.97 to 4.01. Similarly, patients who receive an intra-articular
      corticosteroid injection at the time of surgery are nearly 3 times (OR 2.79) more
      likely to develop a postoperative infection. LEVEL OF EVIDENCE: Level III, case
      control study.

PMID- 28427875
TI  - EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus
      infection.
AB  - Hepatitis B virus (HBV) infection remains a global public health problem with
      changing epidemiology due to several factors including vaccination policies and
      migration. This Clinical Practice Guideline presents updated recommendations for
      the optimal management of HBV infection. Chronic HBV infection can be classified
      into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive
      chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative
      chronic hepatitis and (V) HBsAg-negative phase. All patients with chronic HBV
      infection are at increased risk of progression to cirrhosis and hepatocellular
      carcinoma (HCC), depending on host and viral factors. The main goal of therapy is
      to improve survival and quality of life by preventing disease progression, and
      consequently HCC development. The induction of long-term suppression of HBV
      replication represents the main endpoint of current treatment strategies, while
      HBsAg loss is an optimal endpoint. The typical indication for treatment requires
      HBV DNA >2,000IU/ml, elevated ALT and/or at least moderate histological lesions,
      while all cirrhotic patients with detectable HBV DNA should be treated.
      Additional indications include the prevention of mother to child transmission in
      pregnant women with high viremia and prevention of HBV reactivation in patients
      requiring immunosuppression or chemotherapy. The long-term administration of a
      potent nucleos(t)ide analogue with high barrier to resistance, i.e., entecavir,
      tenofovir disoproxil or tenofovir alafenamide, represents the treatment of
      choice. Pegylated interferon-alfa treatment can also be considered in mild to
      moderate chronic hepatitis B patients. Combination therapies are not generally
      recommended. All patients should be monitored for risk of disease progression and
      HCC. Treated patients should be monitored for therapy response and adherence. HCC
      remains the major concern for treated chronic hepatitis B patients. Several
      subgroups of patients with HBV infection require specific focus. Future treatment
      strategies to achieve 'cure' of disease and new biomarkers are discussed.

PMID- 28427876
TI  - Polar N-terminal Residues Conserved in Type 2 Secretion Pseudopilins Determine
      Subunit Targeting and Membrane Extraction Steps during Fibre Assembly.
AB  - Bacterial type 2 secretion systems (T2SS), type 4 pili, and archaeal flagella
      assemble fibres from initially membrane-embedded pseudopilin and pilin subunits.
      Fibre subunits are made as precursors with positively charged N-terminal anchors,
      whose cleavage via the prepilin peptidase, essential for pilin membrane
      extraction and assembly, is followed by N-methylation of the mature (pseudo)pilin
      N terminus. The conserved Glu residue at position 5 (E5) of mature (pseudo)pilins
      is essential for assembly. Unlike T4 pilins, where E5 residue substitutions also
      abolish N-methylation, the E5A variant of T2SS pseudopilin PulG remains N
      methylated but is affected in interaction with the T2SS component PulM. Here,
      biochemical and functional analyses showed that the PulM interaction defect only
      partly accounts for the PulGE5A assembly defect. First, PulGT2A variant, equally
      defective in PulM interaction, remained partially functional. Furthermore,
      pseudopilus assembly defect of pulG(E5A) mutant was stronger than that of the
      pulM deletion mutant. To understand the dominant effect of E5A mutation, we used
      molecular dynamics simulations of PulGE5A, methylated PulGWT (MePulGWT), and
      MePulGE5A variant in a model membrane. These simulations pointed to a key role
      for an intramolecular interaction between the pseudopilin N-terminal amine and E5
      to limit polar interactions with membrane phospholipids. N-methylation of the N
      terminal amine further limited its interactions with phospholipid head-groups to
      facilitate pseudopilin membrane escape. By binding to polar residues in the
      conserved N-terminal region of PulG, we propose that PulM acts as chaperone to
      promote pseudopilin recruitment and coordinate its membrane extraction with
      subsequent steps of the fibre assembly process.

PMID- 28427877
TI  - Editorial overview: Neurobiology of learning and plasticity 2017.

PMID- 28427878
TI  - Localized degradation of foreign DNA strands in cells: Only excising the first
      nucleotide of 5' region.
AB  - Intracellular delivery of foreign DNA probes sharply increases the efficiency of
      various biodetection protocols. Spherical nucleic acid (SNA) conjugate is a new
      type of probe that consists of a dense oligonucleotide shell attached typically
      to a gold nanoparticle core. They are widely used as novel labels for in vitro
      biodetection and intracellular assay. However, the degradation of foreign DNA
      still remains a challenge that can cause significant signal leakage (false
      positive signal). Hence, the site and behavior of intracellular degradation need
      to be investigated. Herein, we discover a localized degradation behavior that
      only excises the first nucleotide of 5' terminal from a DNA strand, whereas the
      residual portion of this strand is unbroken in MCF-7 cell. This novel degradation
      action totally differs from previous opinion that foreign DNA strand would be
      digested into tiny fragments or even individual nucleotides in cellular
      environment. On the basis of these findings, we propose a simple and effective
      way to avoid degradation-caused false positive that one can bypass the degradable
      site and choose a secure region to label fluorophore along the DNA stand, when
      using DNA probes for intracellular biodetection.

PMID- 28427880
TI  - Evaluation of Effective Microorganisms on home scale organic waste composting.
AB  - Home composting can be an effective way to reduce the volume of municipal solid
      waste. The aim of this study is to evaluate the effect of Effective
      MicroorganismTM (EM) for the home scale co-composting of food waste, rice bran
      and dried leaves. A general consensus is lacking regarding the efficiency of
      inoculation composting. Home scale composting was carried out with and without EM
      (control) to identify the roles of EM. The composting parameters for both trials
      showed a similar trend of changes during the decomposition. As assayed by Fourier
      Transform Infrared Spectroscopy (FTIR), the functional group of humic acid was
      initially dominated by aliphatic structure but was dominated by the aromatic in
      the final compost. The EM compost has a sharper peak of aromatic CC bond
      presenting a better degree of humification. Compost with EM achieved a slightly
      higher temperature at the early stage, with foul odour suppressed, enhanced
      humification process and a greater fat reduction (73%). No significant difference
      was found for the final composts inoculated with and without EM. The properties
      included pH (~7), electric conductivity (~2), carbon-to-nitrogen ratio (C: N <
      14), colour (dark brown), odour (earthy smell), germination index (>100%), humic
      acid content (4.5-4.8%) and pathogen content (no Salmonella, <1000 Most Probable
      Number/g E. coli). All samples were well matured within 2 months. The potassium
      and phosphate contents in both cases were similar however the EM compost has a
      higher nitrogen content (+1.5%). The overall results suggested the positive
      effect provided by EM notably in odour control and humification.

PMID- 28427879
TI  - Food protein-induced enterocolitis syndrome in Australia: A population-based
      study, 2012-2014.
AB  - BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE
      mediated gastrointestinal allergic disorder. Large population-based FPIES studies
      are lacking. OBJECTIVE: We sought to determine the incidence and clinical
      characteristics of FPIES in Australian infants. METHODS: An Australia-wide survey
      (2012-2014) was undertaken through the Australian Paediatric Surveillance Unit,
      with monthly notification of new cases of acute FPIES in infants aged less than
      24 months by 1400 participating pediatricians. RESULTS: Two hundred thirty
      infants with FPIES were identified. The incidence of FPIES in Australian infants
      (<24 months) was 15.4/100,000/y. Median age of first episode, diagnosis, and
      notification were 5, 7, and 10 months, respectively. There was no sex
      predilection. Seven percent of infants had siblings with a history of FPIES, and
      5% reacted during exclusive breast-feeding. Sixty-eight had a single food trigger
      (20% had 2 and 12% had >=3 food triggers). The most common FPIES triggers were
      rice (45%), cow's milk (33%), and egg (12%). Fifty-one percent of infants reacted
      on their first known exposure. Infants with FPIES to multiple versus single food
      groups were younger at the initial episode (4.6 vs 5.8 months [mean], P = .001)
      and more frequently had FPIES to fruits, vegetables, or both (66% vs 21%, P <
      .0001). Infants exclusively breast-fed for more than 4 months had a trend toward
      lower rates of FPIES to multiple food groups (23% vs 36%, P = .06). Sixty-four
      percent of infants with FPIES to multiple foods, which included cow's milk, had
      coassociated FPIES to solid foods. Forty-two percent of infants with FPIES to
      fish reacted to other food groups. CONCLUSIONS: FPIES is not rare, with an
      estimated incidence of 15.4/100,000/y. Rice is the most common food trigger in
      Australia. Factors associated with FPIES to multiple foods included early-onset
      disease and FPIES to fruits, vegetables, or both.

PMID- 28427881
TI  - Association of time from arrest to percutaneous coronary intervention with
      survival outcomes after out-of-hospital cardiac arrest.
AB  - BACKGROUND: Timely post-resuscitation coronary reperfusion therapy is
      recommended; however, the timing of immediate coronary reperfusion for out-of
      hospital cardiac arrest (OHCA) has not been established. We studied the effect of
      the time interval from arrest to percutaneous coronary intervention (PCI) on
      resuscitated OHCA patients. METHODS: All witnessed OHCA patients with a presumed
      cardiac etiology received successful PCI at hospitals between 2013 and 2015,
      excluding cases with unknown information regarding the time from arrest to PCI
      and survival outcomes. The main exposure of interest was the time interval from
      arrest to ballooning or stent placement in coronary arteries, and cases were
      categorized into five groups of 0-90, 90-120, 120-150, and 150-180min and 3-6h.
      The endpoint was survival with good neurological recovery. Multivariable logistic
      regression analysis was performed, adjusting for patient-community, prehospital,
      and hospital factors. RESULTS: A total of 765 patients (24.1% received PCI within
      90min; 31.0% in 90-120min; 17.8% in 120-150min; 12.3% in 150-180min; 14.9% in 3
      6h after arrest) were included. Good neurological recovery was more frequent in
      the early PCI groups than the delayed PCI group (63.6%, 55.3%, 47.8%, 33.0%, and
      42.1%, respectively). The adjusted OR (95% CI) for good neurological recovery
      compared with the most early PCI group was 0.86 (0.53-1.39) in the PCI group
      between 90 and 120min; 0.76 (0.45-1.31) in the PCI group between 120 and 150min;
      0.42 (0.22-0.79) in the PCI group between 150 and 180min; and 0.53 (0.30-0.93) in
      PCI group after 3h. CONCLUSIONS: Among resuscitated OHCA patients with a presumed
      cardiac etiology and successful PCI, patients who received a delayed coronary
      intervention after 150min from arrest were less likely to have neurologically
      intact survival compared to those who received an early intervention.

PMID- 28427882
TI  - Effects of bystander CPR following out-of-hospital cardiac arrest on hospital
      costs and long-term survival.
AB  - BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is associated with a
      greater likelihood of survival to hospital discharge after out-of-hospital
      cardiac arrest (OHCA). However the long-term survival benefits in relationship to
      cost have not been well-studied. We evaluated bystander CPR, hospital-based
      costs, and long-term survival following OHCA in order to assess the potential
      cost-effectiveness of bystander CPR. PATIENTS AND METHODS: We conducted a
      retrospective cohort study of consecutive EMS-treated OHCA patients >=12years who
      arrested prior to EMS arrival and outside a nursing facility between 2001 and
      2010 in greater King County, WA. Utstein-style information was obtained from the
      EMS registry, including 5-year survival. Costs from the OHCA hospitalization were
      obtained from the Washington State Comprehensive Hospital Abstract Reporting
      System. Cost effectiveness was based on hospital costs divided by quality
      adjusted life years (QALYs) for a 5-year follow-up window. RESULTS: Of the 4448
      eligible patients, 18.5% (n=824) were discharged alive from hospital and 12.1%
      (n=539) were alive at 5 years. Five-year survival was higher in patients who
      received bystander CPR (14.3% vs. 8.7%, p<0.001) translating to an average 0.09
      QALYs associated with bystander CPR. The average (SD) total cost of the initial
      acute care hospitalization was USD 19,961 (40,498) for all admitted patients and
      USD 75,175 (52,276) for patients alive at year 5. The incremental cost
      effectiveness ratio associated with bystander CPR was USD 48,044 per QALY.
      CONCLUSION: Based on this population-based investigation, bystander CPR was
      positively associated with long-term survival and appears cost-effective.

PMID- 28427883
TI  - Born not breathing: A randomised trial comparing two self-inflating bag-masks
      during newborn resuscitation in Tanzania.
AB  - AIMS: Effective ventilation is crucial to save non-breathing newborns. We
      compared standard equipment for newborn resuscitation to a new Upright bag, in an
      area with high neonatal mortality. METHODS: Newborns requiring resuscitation at
      Haydom Lutheran Hospital, Tanzania, were ventilated with 230ml standard or 320ml
      Upright bag-mask by weekly non-blinded block randomisation. A Laerdal Newborn
      Resuscitation Monitor collected ventilation data through a flow sensor between
      mask and bag and heart rate with electrocardiography electrodes. Primary outcome
      was expiratory tidal volume per birth weight. RESULTS: Of 6110 babies born, 136
      randomised to standard bag-mask and 192 to Upright, both groups had similar birth
      weight, gestational age, Apgar scores, gender, and mode of delivery. Compared to
      standard bag-mask, Upright gave higher median expiratory tidal volume (8.6ml/kg
      (IQR: 3.5-13.8) vs. 10.0ml/kg (IQR: 4.3-16.8) difference ratio 1.29, 95%CI 1.05,
      1.58, p=0.014)), increased mean airway and peak inspiratory pressures, and higher
      early expired CO2 (median at 20s 4.2% vs. 3.2%, p=0.0099). Clinical outcome 30min
      post-delivery was normal in 44% with standard versus 57% with Upright (p=0.016),
      but similar at 24h. CONCLUSION AND RELEVANCE: Upright provided higher expired
      tidal volume, MAP, PIP and early ECO2 than the standard bag. Clinical outcome
      differed at 30min, but not at 24h. Larger volume of Upright than standard bag can
      be an important factor. The results are relevant for low- and high-income
      settings as ventilatory and heart rate parameters during resuscitation of
      newborns are rarely reported. Trial registered at www.ClinicalTrials.gov,
      NCT01869582.

PMID- 28427884
TI  - Pleural effusion in AA amyloidosis - A rare involvement of a rare disease.

PMID- 28427885
TI  - Prognostic Scoring System to Risk Stratify Parathyroid Carcinoma.
AB  - BACKGROUND: Parathyroid carcinoma is a rare endocrine malignancy that lacks an
      established system for risk categorization. This study evaluated a prognostic
      scoring system for recurrence-free survival (RFS) of patients with parathyroid
      carcinoma. STUDY DESIGN: Patients diagnosed and confirmed to have parathyroid
      carcinoma and who were treated between 1980 and 2016 at The University of Texas
      MD Anderson Cancer Center were studied retrospectively. Univariate and
      multivariate Cox proportional hazards regression analyses of RFS were conducted.
      A prognostic scoring system was created based on multivariate analysis. RESULTS:
      Sixty-eight patients were evaluated. After a median follow-up of 4.6 years, 26
      patients experienced a recurrence. The Kaplan-Meier RFS rates were 85% at 1 year
      (95% CI 77% to 95%), 67% at 2 years (95% CI 55% to 81%), and 51% at 10 years (95%
      CI 36% to 72%) after initial operation. Multivariate analysis demonstrated that
      age older than 65 years, serum calcium level >15 mg/dL, and vascular invasion
      were negatively correlated with RFS rate. Combining these adverse variables into
      a prognostic scoring system, we stratified patients into 3 risk groups: low (0
      variable; 2-year RFS rate, 93%), moderate (1 variable; 2-year RFS rate, 72%), and
      high (2 variables; 2-year RFS rate, 27%) (p = 0.001 [log-rank test]; concordance
      index, 0.70; 95% CI 0.47 to 0.92). CONCLUSIONS: A prognostic scoring system using
      vascular invasion, age, and serum calcium level at initial parathyroidectomy can
      be used to predict RFS. This categorization might be helpful for clinical
      decisions relative to the timing and use of adjuvant therapy. Comprehensive
      validation using multiple cohorts will be needed to confirm applicability.

PMID- 28427886
TI  - Identification of Excipients for Stabilizing Fiberless Adenovirus as
      Biopharmaceuticals.
AB  - Reducing the promiscuous tropism of native adenovirus by using fiberless
      adenovirus is advantageous toward its use as a gene therapy vector or vaccine
      component. The removal of the fiber protein on native adenovirus abrogates
      several undesirable interactions; however, this approach decreases the particle's
      physical stability. To create stable fiberless adenovirus for pharmaceutical use,
      the effects of temperature and pH on the particle's stability profile must be
      addressed. Our results indicate that the stability of fiberless adenovirus is
      increased when it is stored in mildly acidic conditions around pH 6. The
      stability of fiberless adenovirus can be further enhanced by using excipients.
      Excipient screening results indicate that the nonionic surfactant Pluronic F-68
      and the amino acid glycine are potential stabilizers because of their ability to
      increase the thermal transition temperature of the virus particle and promote
      retention of biological activity after exposure to prolonged thermal stress. Our
      data indicate that the instability of fiberless adenovirus can be ameliorated by
      storing the virus in the appropriate environment, and it should be possible to
      further optimize the virus so that it can be used as a biopharmaceutical.

PMID- 28427887
TI  - The detection of antigenic determinants of Acinetobacter baumannii.
AB  - BACKGROUND: Acinetobacter baumannii continues to pose a threat to burdened
      patients in ICUs all around the world. Lately, infection control techniques are
      not sufficient to curb A. baumannii's progression and chemotherapeutics are
      losing their potency against it. Thus, immunization became a key player in
      providing an ideal solution to the dilemma. None of the vaccines under
      investigation have reached the market and the search for a tailored vaccine
      remains a challenge. The notion of unravelling the bacterial antigens to design a
      novel epitope-based vaccine proved its merits. METHODS: In this work, the
      propitious polysaccharide and protein antigenic determinants of A. baumannii were
      mapped by mimicking the infection. The immune response was evaluated by western
      blot, ELISA, and cellular proliferation assay techniques. RESULTS: The screening
      showed that OMPs induced the most eminent sustained IgG response. In addition,
      OMP gave the highest cellular proliferation and a fold increase in ELISA that
      reached up to 10-fold by week 6. Whilst, the LPS gave a rapid IgM response, that
      reached 5-fold and the response was visible from week 1 in the western blot. The
      OMPs had a more pronounced effect in eliciting a cellular immune response.
      CONCLUSION: The results elaborated the valuable role of using pure OMPs and
      detoxified LPS together; as a major cornerstone in designing an ideal vaccine
      against A. baumannii.

PMID- 28427888
TI  - Dopamine elevates intracellular zinc concentration in cultured rat embryonic
      cortical neurons through the cAMP-nitric oxide signaling cascade.
AB  - Zinc ion (Zn2+), the second most abundant transition metal after iron in the
      body, is essential for neuronal activity and also induces toxicity if the
      concentration is abnormally high. Our previous results show that exposure of
      cultured cortical neurons to dopamine elevates intracellular Zn2+ concentrations
      ([Zn2+]i) and induces autophagosome formation but the mechanism is not clear. In
      this study, we characterized the signaling pathway responsible for the dopamine
      induced elevation of [Zn2+]i and the effect of [Zn2+]i in modulating the
      autophagy in cultured rat embryonic cortical neurons. N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine (TPEN), a membrane-permeable Zn2+ chelator, could
      rescue the cell death and suppress the autophagosome puncta number induced by
      dopamine. Dopamine treatment increased the lipidation level of the endogenous
      microtubule-associated protein 1A/1B-light chain 3 (LC3 II), an autophagosome
      marker. TPEN added 1h before, but not after, dopamine treatment suppressed the
      dopamine-induced elevation of LC3 II level. Inhibitors of the dopamine D1-like
      receptor, protein kinase A (PKA), and NOS suppressed the dopamine-induced
      elevation of [Zn2+]i. PKA activators and NO generators directly increased [Zn2+]i
      in cultured neurons. Through cell fractionation, proteins with m.w. values
      between 5 and 10kD were found to release Zn2+ following NO stimulation. In
      addition, TPEN pretreatment and an inhibitor against PKA could suppress the LC3
      II level increased by NO and dopamine, respectively. Therefore, our results
      demonstrate that dopamine-induced elevation of [Zn2+]i is mediated by the D1-like
      receptor-PKA-NO pathway and is important in modulating the cell death and
      autophagy.

PMID- 28427889
TI  - Lost in translation: Cultural divides in communication skills teaching identified
      in the ICCH 2016 student symposium.
AB  - OBJECTIVE: To provide a platform for learners' voices at an international
      conference on communication in healthcare. METHODS: A group of medical students
      were invited to explore their experiences with communication skills learning at a
      symposium at the 2016 International Conference on Communication in Healthcare in
      Heidelberg, DE. RESULTS: Students from the US, Denmark, Germany, and Russia
      discussed their experiences with communication skills curriculum at their
      institutions. We identified divides that have challenged our ability to develop
      and maintain strong communication skills: 1) valuation of communication skills
      vs. other topics, 2) curricular theory vs. practice, 3) evaluation vs. feedback,
      4) preclinical vs. clinical learning, and 5) the medical student vs. practicing
      clinician role. CONCLUSION: The points of transition we identified on the road of
      communication skills teaching highlight opportunities to strengthen the
      educational experience for students. Without an effort to address these divides,
      however, our communication skills may be lost in translation. PRACTICE
      IMPLICATIONS: Students value communication skills teaching during their medical
      education and there are opportunities to translate this to countries that
      currently lack robust curricula and to the real-life post-graduate setting.
      Support is necessary from students, teachers, and administrators, and focus on
      translation of skills during role transitions is needed.

PMID- 28427891
TI  - Local-global processing bias is not a unitary individual difference in visual
      processing.
AB  - A large body of research reports individual differences in local and global
      visual processing in relation to expertise, culture and psychopathology. However,
      recent research has suggested that various different measures of local-global
      processing are not strongly associated with one another, calling its construct
      validity into question. The current study sought to further explore the validity
      of local-global processing biases in perception by developing three tasks based
      on two existing paradigms: the Embedded Figures Test (EFT) and the Navon
      hierarchical letters task. The newly developed tasks aimed to control for
      stimulus and response factors that may have impacted upon the reliability of
      previous research. They were administered to a large sample of undergraduate
      students (N>100). The results of two new versions of the EFT indicated that
      disembedding performance is influenced by the structure of the embedding context.
      In addition, global precedence and interference in the Navon task remained
      present even when local attentional approaches to global hierarchical stimuli
      were restricted. Inter-task correlations within the EFT were high but low between
      the EFT and the Navon task, lending support to the notion that local-global
      processing is not a monolithic construct, but representative of a number of
      distinct perceptual abilities and biases. Future research may use these task
      distinctions to pinpoint more precisely which aspects of perceptual processing
      characterise specific (clinical) participant populations.

PMID- 28427890
TI  - Attentive pointing in natural scenes correlates with other measures of attention.
AB  - Finger pointing is a natural human behavior frequently used to draw attention to
      specific parts of sensory input. Since this pointing behavior is likely preceded
      and/or accompanied by the deployment of attention by the pointing person, we
      hypothesize that pointing can be used as a natural means of providing self
      reports of attention and, in the case of visual input, visual salience. We here
      introduce a new method for assessing attentional choice by asking subjects to
      point to and tap the first place they look at on an image appearing on an
      electronic tablet screen. Our findings show that the tap data are well-correlated
      with other measures of attention, including eye fixations and selections of
      interesting image points, as well as with predictions of a saliency map model. We
      also develop an analysis method for comparing attentional maps (including
      fixations, reported points of interest, finger pointing, and computed salience)
      that takes into account the error in estimating those maps from a finite number
      of data points. This analysis strengthens our original findings by showing that
      the measured correlation between attentional maps drawn from identical underlying
      processes is systematically underestimated. The underestimation is strongest when
      the number of samples is small but it is always present. Our analysis method is
      not limited to data from attentional paradigms but, instead, it is broadly
      applicable to measures of similarity made between counts of multinomial data or
      probability distributions.

PMID- 28427892
TI  - Contour adaptation reduces the spreading of edge induced colors.
AB  - Brief exposure to flickering achromatic outlines of an area causes a reduction in
      the brightness contrast of the surface inside the area. This contour adaptation
      to achromatic contours does not reduce surface contrast when the surface is
      chromatic (the saturation or colorimetric purity of the surface is maintained).
      In addition to reducing the brightness of physical luminance contrast, contour
      adaptation also reduces (or even reverses) the illusory brightness contrast seen
      in the Craik-O'Brien-Cornsweet illusion, in which two physically identical grey
      areas appear different brightness because of a sharp luminance edge separating
      them. Chromatic color spreading illusions also occur with chromatic inducing
      edges, and an unanswered question is whether contour adaptation can reduce the
      perceived contrast of illusory color spreading from edges, even though it cannot
      reduce the perceived contrast of physical surface color. The current studies use
      a color spreading illusion known as the watercolor effect in order to test
      whether illusory color spreading is affected by contour adaptation. The general
      findings of physical achromatic contrast being reduced and chromatic contrast
      being robust to contour adaptation were replicated. However, both illusory
      brightness and color were reduced by contour adaptation, even when the illusion
      edges only differed in chromatic contrast with each other and the background.
      Additional studies adapting to chromatic contours showed opposite effects on
      illusory color contrast than achromatic adaptation.

PMID- 28427893
TI  - Study of acetylcholinesterase activity and apoptosis in SH-SY5Y cells and mice
      exposed to ethanol.
AB  - Ethanol is one of the most commonly abused psychotropic substances with
      deleterious effects on the central nervous system. Ethanol exposure during
      development results in the loss of neurons in brain regions and when exposed to
      ethanol cultured cells undergo apoptosis. To date no information is available on
      whether abnormally high AChE activity is characteristic of apoptosis in animals
      exposed to ethanol. The aims of the present study were to determine whether
      induction of AChE activity is associated with ethanol-induced apoptosis and to
      explore the mechanism of enhanced AChE activity induced by ethanol. For this
      purpose, in vitro and in vivo experiments were performed. AChE activity was
      quantified by spectrophotometry and apoptosis by flow cytometer in SH-SY5Y cells
      exposed to ethanol. The results showed that cells treated with 500mM ethanol for
      24h had a 9-fold increase in apoptotic cells and a 6-fold increase in AChE
      activity compared with controls. Mice exposed acutely to 200MUl of 20% ethanol
      daily on days 1-4 had elevated AChE activity in plasma on days 3-7. On day 4,
      plasma AChE activity was 2.4-fold higher than pretreatment activity. More
      apoptotic cells were found in the brains of treated mice compared to controls.
      Cells in brain sections that were positive in the TUNEL assay stained for AChE
      activity. In conclusion, AChE activity and apoptosis were induced in SH-SY5Y
      cells and mice treated with ethanol, which may indicate that increased AChE may
      related to apoptosis induced by ethanol. Unusually high AChE activity may be an
      effect marker of exposure to ethanol. The relationship between AChE and apoptosis
      might represent a novel mechanism of ethanol-associated neuronal injury.

PMID- 28427894
TI  - In vivo evaluation of central cholinergic circuits in Parkinson's disease using
      transcranial magnetic stimulation.

PMID- 28427895
TI  - Changing cortical inhibition in the course of amyotrophic lateral sclerosis.

PMID- 28427896
TI  - Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter
      pylori infection.
AB  - Toll like receptors (TLRs) are an essential subset of pathogen recognition
      receptors (PRRs) which identify the microbial components and contribute in the
      regulation of innate and adaptive immune responses against the infectious agents.
      The TLRs, especially TLR2, TLR4, TLR5 and TLR9, participate in the induction of
      immune response against H. pylori. TLR2 is expressed on a number of immune and
      non-immune cells and recognizes a vast broad of microbial components due to its
      potential to form heterodimers with other TLRs, including TLR1, TLR6 and TLR10. A
      number of H. pylori-related molecules may contribute to TLR2-dependent responses,
      including HP-LPS, HP-HSP60 and HP-NAP. TLR2 plays a pivotal role in regulation of
      immune response to H. pylori through activation of NF-kappaB and induction of
      cytokine expression in epithelial cells, monocytes/macrophages, dendritic cells,
      neutrophils and B cells. The TLR2-related immune response that is induced by H.
      pylori-derived components may play an important role regarding the outcome of the
      infection toward bacterial elimination, persistence or pathological reactions.
      The immunomodulatory and immunoregulatory roles of TLR2 during H. pylori
      infection were considered in this review. TLR2 could be considered as an
      interesting therapeutic target for treatment of H. pylori-related diseases.

PMID- 28427897
TI  - Boosters and barriers for direct cardiac reprogramming.
AB  - Heart disease is currently the most significant cause of morbidity and mortality
      worldwide, which accounts for approximately 33% of all deaths. Recently, a
      promising and alchemy-like strategy has been developed called direct cardiac
      reprogramming, which directly converts somatic cells such as fibroblasts to
      cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs.
      The first in vitro cardiac reprogramming study, mediated by cardiac transcription
      factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an
      adequate number of fully reprogrammed, functional iCMs. As a result, numerous
      combinations of cardiac TFs exist for direct cardiac reprogramming of mouse and
      human fibroblasts. However, the efficiency of direct cardiac reprogramming
      remains low. Recently, a number of cellular and molecular mechanisms have been
      identified to increase the efficiency of direct cardiac reprogramming and the
      quality of iCMs. For example, microgrooved substrate, cardiogenic growth factors
      [VEGF, FGF, BMP4 and Activin A], and an appropriate stoichiometry of TFs boost
      the direct cardiac reprogramming. On the other hand, serum, TGFbeta signaling,
      activators of epithelial to mesenchymal transition, and some epigenetic factors
      (Bmi1 and Ezh2) are barriers for direct cardiac reprogramming. Manipulating these
      mechanisms by the application of boosters and removing barriers can increase the
      efficiency of direct cardiac reprogramming and possibly make iCMs reliable for
      cell-based therapy or other potential applications. In this review, we summarize
      the latest trends in cardiac TF- or miRNA-based direct cardiac reprogramming and
      comprehensively discuses all molecular and cellular boosters and barriers
      affecting direct cardiac reprogramming.

PMID- 28427898
TI  - Pharmacist impact on pediatric vaccination errors and missed opportunities in the
      setting of clinical decision support.
AB  - OBJECTIVE: To determine pharmacist impact on vaccination errors and missed
      opportunities in the pediatric primary care setting with the presence of clinical
      decision support (CDS) by comparing a clinic with a pharmacist and CDS to a
      clinic with CDS alone. DESIGN: A retrospective chart review of patients'
      electronic medical records compared vaccination errors and missed opportunities
      between 2 pediatric primary care clinics. SETTING: Two urban, pediatric primary
      care clinics were selected for the study. PARTICIPANTS: Encounters were included
      in the analysis for children presenting for any visit over a 3-month period.
      INTERVENTION: The intervention clinic had a full-time clinical pharmacist and
      CDS. The comparison clinic had CDS alone. MAIN OUTCOME MEASURES: Vaccination
      errors were defined as follows: doses administered before minimum recommended
      age, doses administered before minimum recommended dosing interval, unnecessary
      doses, and invalid doses for a combination of these reasons. Missed opportunities
      were defined as vaccine doses due at the date of encounter but not administered,
      without documented reason for vaccination delay or refusal by provider or
      patient. The likelihood of missing an opportunity was also assessed for patient
      age, visit type, and provider type. RESULTS: One thousand and twenty patient
      encounters were randomly selected and reviewed. The vaccination error rate was
      0.4% in the comparison group and 0% in the intervention group (P = 0.4995). The
      number of encounters with a missed opportunity was significantly higher in the
      comparison group compared with the intervention group (51 vs. 30 encounters with
      missed opportunities; P = 0.015; adjusted odds ratio, 2.14 [95% CI 1.3-35]).
      CONCLUSION: Although the use of CDS results in a low rate of vaccination errors,
      technology cannot be solely relied on for vaccination recommendations in the
      pediatric population because of the rigidity of CDS configuration. Pharmacists
      continue to play a vital role to ensure that children are appropriately
      vaccinated in the primary care setting.

PMID- 28427899
TI  - Energy and information flows in biological systems: Bioenergy transduction of V1
      ATPase rotary motor and dynamics of thermodynamic entropy in information flows.
AB  - We classify research fields in biology with respect to flows of materials,
      energy, and information. We investigate energy transducing mechanisms in biology,
      using as a representative the typical molecular rotary motor V1-ATPase from a
      bacterium Enterococcus hirae. The structures of several intermediates of the
      rotary motor are described and the molecular mechanism of the motor converting
      chemical energy into mechanical energy is discussed. Comments and considerations
      on the information flows in biology, especially on the thermodynamic entropy in
      quantum physical and biological systems, are presented in section 3 in a
      biologist friendly manner.

PMID- 28427900
TI  - Molecular cloning and characterization of kiss1 in Brandt's voles (Lasiopodomys
      brandtii).
AB  - Kisspeptin, encoded by kiss1, has been regarded as a major modulator of mammalian
      puberty and fertility due to its stimulation on GnRH. Brandt's vole is one of the
      main pest species on the Inner Mongolian steppes for its striking reproductive
      capacity and kiss1 is a key candidate gene related to reproductive regulatory
      cascades. In this study, kiss1 cDNA was cloned from the hypothalamus of Brandt's
      voles and kiss1 mRNA levels were investigated in different tissues, and at
      different developmental stages, using high-throughput real-time PCR. The full
      length kiss1 cDNA was 682bp, containing an ORF of 405bp, encoding 134 amino acids
      with a conserved kisspeptin-10 region. Kiss1 mRNA was specifically expressed in
      ovary, testicle, small intestine, kidney, liver and hypothalamus tissues, and was
      undetectable in other tissues, including pituitary, heart, adrenal gland, bladder
      and uterus. Sexual organs of both male and female voles enter a period of rapid
      development in the postnatal 4weeks and reach or approach sexual maturity by
      8weeks after birth. Kiss1 mRNA levels in the hypothalamus did not show a
      significant difference between week 2 and week 4, indicating kiss1 mRNA levels
      may not be related to the rapid growth of the sexual organs in early
      developmental stages. Kiss1 transcripts significantly increased in both sexes
      8weeks after birth, and then were maintained at high levels in adults, indicating
      its possible role in the onset of puberty and maintaining of reproductive
      activity. These results are helpful to further the study of kiss1 function in
      reproductive regulation of Brandt's voles.

PMID- 28427901
TI  - The 20kDa and 22kDa forms of human growth hormone (hGH) exhibit different
      intracellular signalling profiles and properties.
AB  - Human Growth Hormone (hGH) includes two main variants. The first is 22kDa GH (22K
      GH), which is predominant in the blood circulation. The second most abundant
      variant is 20K-GH, which makes up 5-10% of the blood circulation. Both bind and
      activate the same receptor, called the human growth hormone receptor (GHR).
      However, the reason why 22K-GH and 20K-GH exhibit similar, but not identical
      physiological activities remains poorly understood. In this article, the
      intracellular signalling profiles between these two hormones were examined.
      Western blot analyses were performed in 3T3-F442A and CHO cells transfected with
      GHR (CHO-GHR). The results revealed that both 22K-GH and 20K-GH can activate
      Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1, 3
      and 5 (STATs 1/3/5). Both induced tyrosine phosphorylation of JAK2 and STAT/1/3/5
      in a time-dependent and dose-dependent manner. However, there were significant
      differences in the intracellular signalling properties between 22K-GH and 20K-GH.
      In particular, the kinetics of signalling shown by 22K-GH and 20K-GH is
      different. In addition, we found that the 20K-GH-induced tyrosine phosphorylation
      of signalling proteins was weaker than that of 22K-GH. Together, these
      observations indicate that the levels and kinetics of phosphorylation mediated by
      the main signalling proteins triggered by 22K-GH or 20K-GH were not exactly the
      same. This may provide a possible explanation for the different biological
      activities exhibited by 22K-GH and 20K-GH.

PMID- 28427902
TI  - Effects of different green light intensities on the growth performance and
      endocrine properties of barfin flounder Verasper moseri.
AB  - We previously reported that the somatic growth of barfin flounder, Verasper
      moseri, was effectively stimulated by the green light compared to the blue and
      red lights. Herein, we report the effects of different green light intensities on
      the growth and endocrine system of the fish. Fish were reared in a dark room with
      light from a light-emitting diode (LED) at a peak wavelength of 518nm under
      controlled photoperiod (10.5:13.5h, light:dark cycle; 06:00-16:30, light) with
      three levels of photon flux density (PFD)-2 (low), 7 (medium), or 21 (high)
      MUmol.m-2.s-1 at the water surface. The average water temperature was 10.2
      degrees C, and the fish were fed until satiety. The fish reared under high PFD of
      green light showed the highest specific growth rates, followed by the medium PFD
      group. Under high PFD, the fish showed the highest amount of melanin
      concentrating hormone mRNA in their brains and insulin in plasma, while the
      lowest amount of growth hormone was observed in their pituitary glands. These
      results suggest that the green light stimulated the growth of barfin flounders in
      a light intensity-dependent manner in association with their central and
      peripheral endocrine systems. However, when the fish were reared in an ordinary
      room where they received both ambient and green LED lights, the fish under LED
      and ambient light grew faster than those under ambient light only (control).
      Moreover, no difference was observed in the specific growth rate of the fish
      reared under the three different green LED light intensities, suggesting that the
      growth was equally stimulated by the green light within a certain range of
      intensities under ambient light.

PMID- 28427903
TI  - Atrial fibrillation is associated with hypermethylation in human left atrium, and
      treatment with decitabine reduces atrial tachyarrhythmias in spontaneously
      hypertensive rats.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular
      mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia
      remains difficult to treat. To identify specific molecular actors involved in AF,
      we have performed a transcriptomic analysis on left atrium (LA) from patients
      with valvular heart disease with or without AF. We showed that 1627 genes had
      altered basal expression level in LA tissue of AF patients compared with the
      control group. The significantly enriched gene ontology biological process
      "anatomical structure morphogenesis" contained the highest number of genes in
      line with changes in structure that occur when the human heart remodels following
      AF development (ie, LA dilatation and interstitial fibrosis). We then focused the
      study on Pitx2 (paired-like homeodomain 2), being the most altered transcription
      factor in LA from AF patients and from which compelling evidence have indicated
      that its reduced expression can be considered as a marker for the disease. In
      addition, its expression was inversely correlated with LA size. We demonstrated
      that AF is associated with Pitx2 promoter hypermethylation both in humans and
      arrhythmic aging spontaneously hypertensive rats. Chronic administration of a DNA
      methylation inhibitor (ie, 5-Aza-2'-deoxycitidine) improved ECG arrhythmic
      profiles and superoxide dismutase activities and reduced fibrosis in the left
      ventricle of spontaneously hypertensive rats. Taken together, these data support
      the notion that AF is associated with epigenetic changes in LA and provide a
      proof-of-concept that hypomethylating agents have to be considered in the
      treatment of atrial arrhythmias.

PMID- 28427905
TI  - Abdominal Aortic Aneurysm Screening Practices: Impact of the 2014 U.S. Preventive
      Services Task Force Recommendations.
AB  - PURPOSE: To assess changes in abdominal aortic aneurysm (AAA) ultrasound
      screening associated with the release of revised U.S. Preventive Services Task
      Force (USPSTF) recommendations on June 24, 2014. METHODS: All AAA screening
      ultrasound examinations performed in the Massachusetts General Hospital radiology
      department in the 15 months before and after the new guidelines were
      retrospectively reviewed to assess changes in examination volume and
      appropriateness, demographics, aneurysm detection rate and size at diagnosis,
      frequency and type of incidental findings, and radiologist recommendations.
      Examinations were considered "definitely appropriate" if meeting USPSTF grade "B"
      evidence and "possibly appropriate" if meeting grade "C" or "I" evidence, based
      on available guidelines. Means were compared with the t test. RESULTS: A total of
      831 examinations were reviewed, 417 (50.2%) performed before and 414 (49.8%)
      after the new guidelines, with overall mean (SD) subject age 67.9 (6.8) years,
      89.2% male. Appropriate examinations increased from 289 of 417 (69.3%) to 313 of
      414 (75.6%) after the new guidelines (P = .04), mostly due to definitely
      appropriate examinations (253/417 [60.7%] versus 286/414 [69.1%], P = .01).
      Aneurysm detection rates increased from 23 of 417 (5.5%) to 39 of 414 (9.4%), P =
      .03. Mean (SD) aneurysm size (cm) at diagnosis decreased from 3.8 (0.7) to 3.3
      (0.6), P = .01. Examination volume, demographics, and rates of incidentals and
      recommendations remained similar. Incidentals arose in 15.4% of all examinations,
      often iliac artery aneurysms or renal masses. Recommendations were made in 5.1%,
      mostly for cross-sectional imaging. CONCLUSIONS: The revised USPSTF guidelines
      have been associated with increased AAA screening appropriateness and aneurysm
      detection in our practice, with smaller aneurysm size at diagnosis.

PMID- 28427904
TI  - Leishmania donovani tyrosyl-tRNA synthetase structure in complex with a tyrosyl
      adenylate analog and comparisons with human and protozoan counterparts.
AB  - The crystal structure of Leishmania donovani tyrosyl-tRNA synthetase (LdTyrRS) in
      complex with a nanobody and the tyrosyl adenylate analog TyrSA was determined at
      2.75 A resolution. Nanobodies are the variable domains of camelid heavy chain
      only antibodies. The nanobody makes numerous crystal contacts and in addition
      reduces the flexibility of a loop of LdTyrRS. TyrSA is engaged in many
      interactions with active site residues occupying the tyrosine and adenine binding
      pockets. The LdTyrRS polypeptide chain consists of two pseudo-monomers, each
      consisting of two domains. Comparing the two independent chains in the asymmetric
      unit reveals that the two pseudo-monomers of LdTyrRS can bend with respect to
      each other essentially as rigid bodies. This flexibility might be useful in the
      positioning of tRNA for catalysis since both pseudo-monomers in the LdTyrRS chain
      are needed for charging tRNATyr. An "extra pocket" (EP) appears to be present
      near the adenine binding region of LdTyrRS. Since this pocket is absent in the
      two human homologous enzymes, the EP provides interesting opportunities for
      obtaining selective drugs for treating infections caused by L. donovani, a
      unicellular parasite causing visceral leishmaniasis, or kala azar, which claims
      20,000 to 30,000 deaths per year. Sequence and structural comparisons indicate
      that the EP is a characteristic which also occurs in the active site of several
      other important pathogenic protozoa. Therefore, the structure of LdTyrRS could
      inspire the design of compounds useful for treating several different parasitic
      diseases.

PMID- 28427906
TI  - Factors Influencing the Gender Breakdown of Academic Radiology Residency
      Programs.
AB  - PURPOSE: To determine the gender distribution of radiology residency programs and
      identify associations with radiology departmental factors. METHODS: The residency
      programs affiliated with the top 50 research medical school from US News and
      World Report were identified. The gender of all radiology residency graduates
      from each program from 2011 to 2015 were collected. Radiology departmental
      factors were collected: gender of chairperson, gender of program director, gender
      of faculty, geographic location, and city population of the residency program.
      The median percentage of female radiology faculty and residents were calculated
      and classified as above or below the median. Comparisons were made between
      residency programs and departmental factors via a Pearson chi2 univariate test or
      logistic regression. RESULTS: There were 618 (27.9%) female and 1,598 (72.1%)
      male residents in our study, with a median female representation of 26.4% in each
      program. Programs with a female residency program director were significantly
      more likely to have an above-median percentage of female residents versus a male
      program director (68.4% versus 38.7%, P = .04). Programs in the Northeast (70.6%)
      and West (70.0%) had higher above-median female representation than the South
      (10.0%) and Midwest (38.5%, P < .01). There was no association with city
      population size (P = .40), gender of faculty (P = .40), residency size (P = .91),
      or faculty size (P = .15). CONCLUSION: Radiology residency programs with a female
      residency program director and those in the Northeast or West have a greater
      concentration of female residents. Residency programs that aim to increase female
      representation should investigate modifiable factors that can improve their
      recruitment practices.

PMID- 28427907
TI  - Analysis of the Completeness and Clarity of Free-Form Radiology Dictations for
      the Reporting of Pulmonary Embolism.

PMID- 28427908
TI  - Transforming the Health Care Experience: Doctors, Nurses, Patients, and Beyond.

PMID- 28427909
TI  - Improving the Interventional Radiology Patient Experience: Effect of a Phone
      Communication System Revision.

PMID- 28427910
TI  - Stochasticity of gene expression as a motor of epigenetics in bacteria: from
      individual to collective behaviors.
AB  - Measuring gene expression at the single cell and single molecule level has
      recently made possible the quantitative measurement of stochasticity of gene
      expression. This enables identification of the probable sources and roles of
      noise. Gene expression noise can result in bacterial population heterogeneity,
      offering specific advantages for fitness and survival in various environments.
      This trait is therefore selected during the evolution of the species, and is
      consequently regulated by a specific genetic network architecture. Examples exist
      in stress-response mechanisms, as well as in infection and pathogenicity
      strategies, pointing to advantages for multicellularity of bacterial populations.

PMID- 28427912
TI  - Hepataprotective effects of ginsenoside Rg1 - A review.
AB  - BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng has been used as efficient
      tonic and for the treatment of various diseases including hepatic disorders.
      Ginseng saponins, also known as ginsenosides, are principal constituents and have
      been treated to be responsible for disparate ginseng health benefits. The current
      review mainly focuses on ginsenoside Rg1, a compound isolated from traditional
      Chinese herbal medicine Panax ginseng Meyer. AIMS: To summary the
      hepataprotective effects and related mechanisms of ginsenoside Rg1, we conclude
      this review by combining the literature and our own researches. METHODS: As
      evidenced, we organized the pharmacological function of ginsenoside Rg1 by
      searching the pubmed. It has been deeply studied and summarized in the field of
      neurobiology, however, in this paper we described the pharmacological function of
      Rg1 in liver related to antioxidative stress and anti-inflammation. R&D:
      Individual ginsenoside could be used since it shows a wide array of beneficial
      functions in the regulation and disorders of acute and chronic hepatotoxicity,
      hepatitis, hepatic fibrosis and cirrhosis in various pathways and different
      mechanisms. Of note, the antioxidant hepatic protection of ginsenoside Rg1 is
      mainly through the induction of Keap1-Nrf2-ARE signaling pathway. CONCLUSION: The
      multi-target actions of Rg1 substantiates it as a promising drug candidate for
      the treatment of hepatic impairment in different factors induced liver diseases.

PMID- 28427911
TI  - Safety parameter considerations of anodal transcranial Direct Current Stimulation
      in rats.
AB  - A commonly referenced transcranial Direct Current Stimulation (tDCS) safety
      threshold derives from tDCS lesion studies in the rat and relies on electrode
      current density (and related electrode charge density) to support clinical
      guidelines. Concerns about the role of polarity (e.g. anodal tDCS), sub-lesion
      threshold injury (e.g. neuroinflammatory processes), and role of electrode
      montage across rodent and human studies support further investigation into animal
      models of tDCS safety. Thirty-two anesthetized rats received anodal tDCS between
      0 and 5mA for 60min through one of three epicranial electrode montages. Tissue
      damage was evaluated using hemotoxylin and eosin (H&E) staining, Iba-1
      immunohistochemistry, and computational brain current density modeling. Brain
      lesion occurred after anodal tDCS at and above 0.5mA using a 25.0mm2 electrode
      (electrode current density: 20.0A/m2). Lesion initially occurred using smaller
      10.6mm2 or 5.3mm2 electrodes at 0.25mA (23.5A/m2) and 0.5mA (94.2A/m2),
      respectively. Histological damage was correlated with computational brain current
      density predictions. Changes in microglial phenotype occurred in higher
      stimulation groups. Lesions were observed using anodal tDCS at an electrode
      current density of 20.0A/m2, which is below the previously reported safety
      threshold of 142.9A/m2 using cathodal tDCS. The lesion area is not simply
      predicted by electrode current density (and so not by charge density as duration
      was fixed); rather computational modeling suggests average brain current density
      as a better predictor for anodal tDCS. Nonetheless, under the assumption that
      rodent epicranial stimulation is a hypersensitive model, an electrode current
      density of 20.0A/m2 represents a conservative threshold for clinical tDCS, which
      typically uses an electrode current density of 2A/m2 when electrodes are placed
      on the skin (resulting in a lower brain current density).

PMID- 28427914
TI  - [Determinants of caregiver burden. Study of gender differences].

PMID- 28427913
TI  - Predicting the stone composition of children preoperatively by Hounsfield unit
      detection on non-contrast computed tomography.
AB  - INTRODUCTION: Many studies have been performed on adult patients to reveal the
      relationship between Hounsfield unit (HU) value and composition of stone, but
      none have focused on childhood. OBJECTIVE: We aimed to predict stone composition
      by HU properties in pre-intervention non-contrast computed tomography (NCCT) in
      children. This could help to orient patients towards more successful
      interventions. MATERIALS AND METHODS: Data of 94 children, whose pre-intervention
      NCCT and post-interventional stone analysis were available were included. Stones
      were grouped into three groups: calcium oxalate (CaOx), cystine, and struvite.
      Besides spot urine PH value, core HU, periphery HU, and Hounsfield density (HUD)
      values were measured and groups were compared statistically. RESULTS: The mean
      age of patients was 7 +/- 4 (2-17) years and the female/male ratio was 51/43. The
      mean stone size was 11.7 +/- 5 (4-24) mm. There were 50, 38, and 6 patients in
      the CaOx, cystine, and struvite groups, respectively. The median values for core
      HU, periphery HU, and mean HU in the CaOx group were significantly higher than
      the corresponding median values in the cystine and struvite groups. Significant
      median HUD difference was seen only between the CaOx and cystine groups. No
      difference was seen between the cystine and struvite groups in terms of HU
      parameters. To distinguish these groups, mean spot urine PH values were compared
      and were found to be higher in the struvite group than the cystine group (Table).
      DISCUSSION: The retrospective nature and small number of patients in some groups
      are limitations of this study, which also does not include all stone
      compositions. Our cystine stone rate was higher than childhood stone composition
      distribution in the literature. This is because our center is a reference center
      in a region with high recurrence rates of cystine stones. In fact, high numbers
      of cystine stones helped us to compare them with calcium stones more accurately
      and became an advantage for this study. CONCLUSIONS: NCCT at diagnosis can
      provide some information for determination of stone composition. While CaOx
      stones can be discriminated from cystine and struvite stones using HU parameters,
      a simple spot urine pH assessment must be added to distinguish cystine stones
      from struvite stones.

PMID- 28427915
TI  - [Multimorbidity in general practice and the Ariadne principles. A person-centred
      approach].
AB  - Multimorbidity, defined as the coexistence of two or more chronic conditions in
      one same individual, has negative consequences for people suffering from it and
      it poses a real challenge for health systems. In primary care, where most of
      these patients are attended, the clinical management of multimorbidity can be a
      complex task due, among others, to the high volume of clinical information that
      needs to be handled, the scarce scientific evidence available to approach
      multimorbidity, and the need for coordination among multiple health providers to
      guarantee continuity of care. Moreover, the adequate implementation of the care
      plan in these patients requires a process of shared decision making between
      patient and physician. One of the available tools to support this process, which
      is specifically directed to patients with multimorbidity in primary care, is
      described in the present article: the Ariadne principles.

PMID- 28427916
TI  - [Actinic keratosis: New concept and therapeutic update].
AB  - Actinic keratosis (AK) is a common reason for consultation in both Primary Care
      and Specialised Care. It is the third or fourth most common reason for
      consultation in dermatology, accounting for up to 5-6% of patients attended. It
      has also been observed that its prevalence has been increasing in the last
      10years, compared to other dermatoses. This is also expected to continue to
      increase due to longer life expectancy, and by the changes in sun exposure habits
      since the middle of the last century. The aim of this article is to update the
      concepts of AK, cancerisation field and to present the currently available
      therapeutic tools.

PMID- 28427917
TI  - Application of the isoniazid assay in dried blood spots using the ultra
      performance liquid chromatography-tandem mass spectrometry.
AB  - OBJECTIVES: Therapeutic drug monitoring (TDM) of anti-tuberculosis (TB) drugs is
      important for proper treatment of TB. Dried blood spots (DBSs) are widely used
      for TDM because of their several advantages. Rifampicin and pyrazinamide assays
      with DBSs have already been developed. However, isoniazid (INH) assay for
      capillary DBSs have not been reported because of INH instability. We developed an
      ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      method for measuring INH concentrations in venous and capillary DBSs. METHODS:
      Each DBS was analyzed on an UPLC system. INH and internal standard (IS)
      concentrations were determined by multiple-reaction monitoring in positive ion
      mode. Analytical performances, including precision, linearity, and comparison of
      different types of specimens were determined. Further, the stability of INH in
      venous DBSs was tested. RESULTS: INH and IS were clearly separated in the UPLC
      MS/MS system without matrix effect. Within-run precision and between-day
      precision were 2.68-8.02% and 2.54-5.45%, respectively. INH concentrations in
      venous DBS showed proportional bias compared with those in plasma (Slope: 0.8704)
      with good correlation. INH concentration in capillary DBS was slightly but not
      significantly higher than that in venous DBS. CONCLUSIONS: The findings of our
      study show that the analytical performance of this novel method for capillary and
      venous DBSs was clinically acceptable for the TDM of INH.

PMID- 28427918
TI  - Endocan is a stable circulating molecule in ICU patients.
AB  - BACKGROUND: Endocan is a lung endothelial cell secreted proteoglycan, possessing
      multiple physiological roles and potential therapeutic and diagnostic utility as
      biomarker in pneumonia and acute respiratory distress syndrome. Endocan synthesis
      and secretion can be induced by proinflammatory cytokines such as TNF-alpha, but
      can also be subject of proteolytic degradation causing preanalytical variation.
      METHODS: We investigated the stability of endocan in conventional serum, plasma,
      anticoagulated whole blood, as well as whole blood and plasma stabilized with
      protease inhibitors. RESULTS: Among the recipient tubes for blood collection,
      those with EDTA gave minimal interference. No dilution effect was observed on
      recovery tests from 1:2 to 1:16 (v:v). The recovery test in 10 plasma EDTA
      samples from healthy subjects or septic patients indicated a median recovery of
      104.5% [104%-107.5%], and 97% [88.5%; 102.5%], respectively. Patient's plasma
      endocan remains stable when stored at room temperature till 72h, or following 3
      freeze thaw cycles. Finally, no interference was observed with hemolytic, icteric
      or turbidic plasma samples. CONCLUSION: These results are consistent with the
      view that endocan measured in ICU patients is intact, stable, and accurate. Then,
      the low endocan level observed in ICU patients who developed ARDS is likely to be
      reliable.

PMID- 28427919
TI  - Introduction to the 2016 SSIB special issue.

PMID- 28427920
TI  - Genome improvement of the acarbose producer Actinoplanes sp. SE50/110 and
      annotation refinement based on RNA-seq analysis.
AB  - Actinoplanes sp. SE50/110 is the natural producer of acarbose, which is used in
      the treatment of diabetes mellitus type II. However, until now the
      transcriptional organization and regulation of the acarbose biosynthesis are only
      understood rudimentarily. The genome sequence of Actinoplanes sp. SE50/110 was
      known before, but was resequenced in this study to remove assembly artifacts and
      incorrect base callings. The annotation of the genome was refined in a multi-step
      approach, including modern bioinformatic pipelines, transcriptome and proteome
      data. A whole transcriptome RNA-seq library as well as an RNA-seq library
      enriched for primary 5'-ends were used for the detection of transcription start
      sites, to correct tRNA predictions, to identify novel transcripts like small RNAs
      and to improve the annotation through the correction of falsely annotated
      translation start sites. The transcriptome data sets were also applied to
      identify 31 cis-regulatory RNA structures, such as riboswitches or RNA
      thermometers as well as three leaderless transcribed short peptides found in
      putative attenuators upstream of genes for amino acid biosynthesis. The
      transcriptional organization of the acarbose biosynthetic gene cluster was
      elucidated in detail and fourteen novel biosynthetic gene clusters were
      suggested. The accurate genome sequence and precise annotation of the
      Actinoplanes sp. SE50/110 genome will be the foundation for future genetic
      engineering and systems biology studies.

PMID- 28427921
TI  - Enhancement of ethyl (S)-4-chloro-3-hydroxybutanoate production at high substrate
      concentration by in situ resin adsorption.
AB  - Asymmetric reduction of ethyl 4-chloro-3-oxobutyrate (COBE) by carbonyl
      reductases presents an efficient way to produce Ethyl (S)-4-chloro-3
      hydroxybutanoate ((S)-CHBE), an important chiral intermediate for the synthesis
      of hydroxymethylglutaryl-CoA reductase inhibitors such as Lipitor(r). In this
      study, an NADPH-dependent carbonyl reductase (SrCR) from Synechocystis sp. was
      characterized to demonstrate a broad substrate spectrum, and the highest activity
      (53.1U/mg protein) with COBE. To regenerate the cofactor NADPH, Bacillus subtilis
      glucose dehydrogenase was successfully coexpressed with SrCR. Owing to the
      product inhibition, no more than 400mM of COBE could be completely reduced to (S)
      CHBE using the recombinant Escherichia coli/pET-SrCR-GDH. The macroporous
      adsorption resin HZ 814 was applied to adsorb (S)-CHBE in situ to alleviate the
      product inhibitio. Consequently, 3000mM (494g/L) of COBE was bioconverted within
      8h, resulting in a (S)-CHBE yield of 98.2%, with 99.4% ee and total turnover
      number of 15,000, revealed great industrial potential of (S)-CHBE production.

PMID- 28427922
TI  - [Sudden-onset bullous pemphigoid in a 12-year-old child].
AB  - Bullous pemphigoid (BP) is an acquired autoimmune disease that mainly affects the
      elderly. It is very rare in children. We report a sudden polymorphic case of BP
      in a 12-year-old child.

PMID- 28427923
TI  - [Acute leukemia revealed by bone magnetic resonance imaging: Two pediatric case
      reports].
AB  - Bone and joint pain are common causes of pediatric consultation for a variety of
      etiologies. The causes are mostly traumatic or infectious or have an inflammatory
      origin. Acute leukemia (AL) can sometimes begin with osteoarticular signs and
      radiological investigations such as magnetic resonance imaging (MRI) can help
      guide the diagnosis. We report on two cases of pediatric AL revealed by
      osteoarticular signs, with MRI helpful in the diagnostic procedure. In these
      children, the first signs were recurrent joint pain, with no blood count
      anomalies. There was a delay between the onset of arthralgia and diagnosis due to
      atypical presentation of the disease. MRI guided the investigations to the
      diagnosis of AL. The persistence of pain or inflammation must lead to considering
      a bone MRI and a complete blood count must be repeated in case of persistent
      inflammatory bone pain to avoid a missed diagnosis of blood disease.

PMID- 28427924
TI  - Long-Term Deterioration of Perceived Health and Functioning in Adults With
      Cerebral Palsy.
AB  - OBJECTIVE: To describe longitudinal change in perceived health, presence of
      health issues, and functional level in adults with cerebral palsy (CP). DESIGN:
      Prospective cohort study. SETTING: Participants' daily environment. PARTICIPANTS:
      Adults (N=49) with CP (age range, 35-45y; 27 [55%] men; 36 [75%] spastic)
      formerly known in pediatric rehabilitation care participated. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Postal questionnaires were completed by the
      adults or their proxies (n=9). Health outcomes included perceived health (adapted
      from the 36-Item Short Form Health Survey) and presence of health issues such as
      pain, severe fatigue (dichotomized), and functional level (Barthel Index; walking
      performance). RESULTS: Over a 10-year period, the percentage of adults with CP
      worrying about their health increased (29%-54%; P=.008) and those indicating that
      health problems limit their activities increased (19%-45%; P=.002). In the same
      period, most adults continued to report good general health (93%-86%; P=.148).
      Presence of some health issues increased over time, such as pain; severe fatigue
      was a common health issue at follow-up (32%). Over a 14-year period, mobility and
      self-care deteriorated (Barthel Index, 17.1+/-4.8 to 16.3+/-5.6; P=.007). Walking
      performance, specifically indoors, declined (83%-71%; P=.010). CONCLUSIONS:
      Adults with CP experienced deterioration in health outcomes in the long term.
      Most notably, perceived health and functional level decreased. Pain and severe
      fatigue were the most common health issues in adult CP. More research is required
      to explore the mechanisms at work in the process of aging in persons with CP.
      Systematic follow-up of adults with CP appears necessary to timely detect and
      intervene in health problems and functional decline.

PMID- 28427926
TI  - Effects of Home-Based Supportive Care on Improvements in Physical Function and
      Depressive Symptoms in Patients With Stroke: A Meta-Analysis.
AB  - OBJECTIVE: To examine the effects of home-based supportive care on improvements
      in physical function and depressive symptoms in home-dwelling patients after
      stroke. DATA SOURCES: Seven electronic databases (eg, MEDLINE, PubMed, CINAL,
      EMBASE, the Cochrane Central Register of Controlled Trials, ProQuest, and Google
      Scholar) and 4 Chinese databases (eg, WANFANG MED ONLINE, Chinese Electronic
      Periodical Services, China Academic Journals Full-text Database, and National
      Central Library) were fully searched for all relevant articles up to June 25,
      2016. STUDY SELECTION: Randomized controlled trials examining the effects of home
      based supportive care on physical function and depressive symptoms in home
      dwelling patients after stroke were included. Finally, 16 articles in Chinese
      (n=4) and English (n=12) met the inclusion criteria. DATA EXTRACTION: Data on
      patient characteristics, study characteristics, intervention details, and outcome
      were extracted. Two reviewers independently extracted data and assessed
      methodological quality using the Cochrane risk of bias tool. DATA SYNTHESIS: Home
      based supportive care had a small size effect on physical function (Hedges'
      g=.17; 95% confidence interval, .09-.26) and a moderate size effect on depressive
      symptoms (Hedges' g=-.44; 95% confidence interval, -.83 to -.05) in home-dwelling
      patients after stroke. The moderator analysis revealed that some components of
      study participants and intervention programs improved the effects on physical
      function and depressive symptoms; however, no significant moderators were further
      identified to have superiorly improved physical function and depressive symptoms.
      CONCLUSIONS: Regular performance of home-based supportive interventions should be
      considered for inclusion as routine care for managing and improving physical
      function and depressive symptoms in home-dwelling patients after stroke. The
      present findings provide further evidence with which to design appropriate
      supportive interventions for home-dwelling stroke survivors.

PMID- 28427927
TI  - Development and Preliminary Psychometrics of the Exercise Therapy Burden
      Questionnaire for Patients With Chronic Conditions.
AB  - OBJECTIVE: To develop and validate a self-reporting questionnaire assessing the
      burden of exercise therapy for patients with chronic conditions. DESIGN:
      Measurement properties of an instrument. SETTING: Outpatient clinics and tertiary
      care hospital. PARTICIPANTS: Patients (N=201) with at least 1 chronic condition
      and performing exercise therapy. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The dimensional structure of the questionnaire was assessed by
      principal component analysis. Construct validity of the instrument was assessed
      by exploring convergent validity with the Treatment Burden Questionnaire (TBQ)
      and divergent validity with pain, self-efficacy, treatment satisfaction, and
      health state. Reliability was assessed with the Cronbach alpha coefficient, a
      test-retest method using the intraclass correlation coefficient (ICC), and Bland
      Altman plotting. RESULTS: A preliminary list of items was developed from
      semistructured interviews with 28 patients and reviewed by 2 expert physicians.
      Items obtained were reduced. Then a sample of 163 patients was used to measure
      the psychometrics of the Exercise Therapy Burden Questionnaire (ETBQ), consisting
      of 10 items. Principal component analysis extracted 1 dimension. The Cronbach
      alpha was .86 (.82-.89). Test-retest reliability (n=24 patients) was good with an
      ICC of .93 (.85-.97), and Bland-Altman analysis did not reveal a systematic
      trend. The ETBQ showed expected convergent validity with the TBQ (rho=.52) and
      expected divergent validity with pain (rho=.37), self-efficacy (rho=-.34),
      treatment satisfaction (rho=-.49), and perceived health state (rho=-.28).
      CONCLUSIONS: The ETBQ is the first questionnaire assessing exercise therapy
      burden in patients with chronic conditions. Its psychometric properties are
      promising.

PMID- 28427925
TI  - Effect of Home- and Community-Based Physical Activity Interventions on Physical
      Function Among Cancer Survivors: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To examine the effect of home- and community-based physical activity
      interventions on physical functioning among cancer survivors based on the most
      prevalent physical function measures, randomized trials were reviewed. DATA
      SOURCES: Five electronic databases-Medline Ovid, PubMed, CINAHL, Web of Science,
      and PsycINFO-were searched from inception to March 2016 for relevant articles.
      STUDY SELECTION: Search terms included community-based interventions, physical
      functioning, and cancer survivors. A reference librarian trained in systematic
      reviews conducted the final search. DATA EXTRACTION: Four reviewers evaluated
      eligibility and 2 reviewers evaluated methodological quality. Data were
      abstracted from studies that used the most prevalent physical function
      measurement tools-Medical Outcomes Study 36-Item Short-Form Health Survey, Late
      Life Function and Disability Instrument, European Organisation for the Research
      and Treatment of Cancer Quality-of-Life Questionnaire, and 6-minute walk test.
      Random- or fixed-effects models were conducted to obtain overall effect size per
      physical function measure. DATA SYNTHESIS: Fourteen studies met inclusion
      criteria and were used to compute standardized mean differences using the inverse
      variance statistical method. The median sample size was 83 participants. Most of
      the studies (n=7) were conducted among breast cancer survivors. The interventions
      produced short-term positive effects on physical functioning, with overall effect
      sizes ranging from small (.17; 95% confidence interval [CI], .07-.27) to medium
      (.45; 95% CI, .23-.67). Community-based interventions that met in groups and used
      behavioral change strategies produced the largest effect sizes. CONCLUSIONS: Home
      and community-based physical activity interventions may be a potential tool to
      combat functional deterioration among aging cancer survivors. More studies are
      needed among other cancer types using clinically relevant objective functional
      measures (eg, gait speed) to accelerate translation into the community and
      clinical practice.

PMID- 28427928
TI  - Objective Versus Subjective Measures of Executive Functions: Predictors of
      Participation and Quality of Life in Parkinson Disease?
AB  - OBJECTIVES: To determine whether objective (neuropsychological tests) and
      subjective measures (questionnaires) of executive functions (EFs) are associated
      in patients with Parkinson disease (PD), and to determine to what extent level of
      participation and quality of life (QoL) of patients with PD can be predicted by
      these measures of EFs. DESIGN: Correlational research design (case-control and
      prediction design). SETTING: Departments of neuropsychology of 3 medical centers.
      PARTICIPANTS: A sample (N=136) of patients with PD (n=42) and their relatives,
      and controls without PD (n=94). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: A test battery measuring EFs. In addition, patients, their relatives,
      and controls completed the Dysexecutive Questionnaire, Brock Adaptive Functioning
      Questionnaire, and Barkley Deficits in Executive Functioning Scale - time
      management questionnaires measuring complaints about EFs. Participation and QoL
      were measured with the Impact on Participation and Autonomy scale and the
      Parkinson's Disease Questionnaire-39, respectively. RESULTS: Patients with PD
      showed impairments in EFs on objective tests and reported significantly more
      complaints about EFs than did controls without PD. No associations were found
      between patients' performances on objective and subjective measures of EFs.
      However, both objective and subjective measures predicted patients' level of
      participation. In addition, subjective measures of EFs predicted QoL in patients
      with PD. CONCLUSIONS: These findings show that objective and subjective measures
      of EFs are not interchangeable and that both approaches predict level of
      participation and QoL in patients with PD. However, within this context, sex
      needs to be taken into account.

PMID- 28427929
TI  - Corrigendum to "Long-term cariprazine treatment for the prevention of relapse in
      patients with schizophrenia: A randomized, double-blind, placebo-controlled
      trial" [Schizophr. Res. 176 (2016) 264-271].

PMID- 28427930
TI  - The relative prevalence of schizophrenia among cannabis and cocaine users
      attending addiction services.
AB  - BACKGROUND: Cannabis and cocaine are the most common illicit drugs for which
      people are treated in addiction services in Latin America. Much research has
      suggested that the use of cannabis increases the risk of schizophrenia; there is
      less evidence concerning cocaine. The aim of the present study was to establish
      the relative prevalence of schizophrenia in people treated for cannabis use and
      cocaine use disorders in Chile. METHODS: A sample of 22,615 people treated for
      illicit drug use disorders was obtained from a national registry of addiction
      service users in Chile. Clinical diagnoses were established at admission to
      substance use treatment programs or at any point during the period of treatment.
      Prevalence rates of schizophrenia and related disorders, and affective disorders
      were calculated for the groups of people with cocaine use disorders, and cannabis
      use disorders. Odds ratios (OR) for schizophrenia and for affective disorders
      were calculated for cannabis users using the group of people treated for cocaine
      use disorders as reference category. RESULTS: The prevalence of schizophrenia and
      related disorders was 1.1% in those with cocaine use disorders, but 5.2% in those
      with cannabis use disorders (OR 4.9; p<0.01). The prevalence of affective
      disorders was 9.3% in cocaine use disorders, and 13.2% in cannabis use disorders
      (OR 1.5; p<0.01). CONCLUSIONS: The prevalence of schizophrenia and to a lesser
      extent affective disorders is higher among people with cannabis use disorder than
      cocaine use disorder among those attending addiction services.

PMID- 28427931
TI  - Issues affecting reliable and valid assessment of early life stressors in
      psychosis.

PMID- 28427932
TI  - Reciprocal changes in noradrenaline and GABA levels in discrete brain regions
      upon rapid eye movement sleep deprivation in rats.
AB  - Rapid eye movement sleep (REMS) plays important role in maintenance of normal
      brain functions. Neurons containing various neurotransmitters in different brain
      regions interact to regulate this complex phenomenon in health and diseases. The
      number of neuronal projections, their firing rates and neurotransmitter levels
      vary in different brain regions under various conditions leading to normal or
      altered patho-physio-behavioral states. In this study using high performance
      liquid chromatography (HPLC) we quantified noradrenaline (NA) and gamma-amino
      butyric acid (GABA) levels in locus coeruleus (LC), dorsal raphe (DR), pedunculo
      pontine tegmentum (PPT), frontal lobe (FL), cortex and hippocampus (Hippo) in
      control and after 96 h REMS deprivation (REMSD) rats. Normal free moving control
      (FMC) rats were taken as standard cage controls. To rule out non-specific effects
      large platform control (LPC) and post-REMSD recovery (REC) were carried out. The
      levels of NA and GABA in discrete brain regions upon REMSD were statistically
      compared with all the controls. Upon REMSD, although NA levels significantly
      increased and the GABA levels decreased in the LC, PPT and cortex, in Hippo their
      levels showed opposite responses. Only NA levels increased in FL, while only GABA
      levels were decreased in the DR after REMSD. Most of the altered neurotransmitter
      levels returned to normal levels in REC rats. The findings help understanding the
      neurochemical basis of REMSD and its associated effects.

PMID- 28427933
TI  - High molecular weight genomic DNA mini-prep for filamentous fungi.
AB  - Purification of high quality genomic DNA (gDNA) from filamentous fungi suitable
      for whole genome sequencing has previously involved many steps. Here, we report a
      simple and easy-to-follow mini-preparation protocol for high molecular weight
      (~20kb) gDNA from filamentous fungi including Aspergillus and Eurotium. This
      comprehensive protocol includes graphic step-by-step instructions for
      inoculation, homogenization, and purification of gDNA. The most critical step is
      a thorough 3-5min homogenization of the freeze-dried mycelium using a motorized
      hand-held homogenizer with a mini spatula inserted. Approximately 20mg of the
      fine mycelial powder is then subjected to a modified procedure for the DNeasy
      Plant Mini Kit (Qiagen). This Qiagen spin column protocol avoids precipitation,
      dryness, and resuspension of gDNA, which can cause shearing and loss of gDNA.
      Final gDNA yields from ~20mg of fine mycelial powder are 8 to 20MUg with a
      consistent 260/280nm absorbance ratio of ~1.9. All 30 gDNA samples we purified
      using our method were of high molecular weight (~20kb). Whole genome sequencing
      of these DNA samples resulted in 160-260 X coverage with 2*150 reads using
      NextSeq 500. These gDNAs are also of a suitable quality for Southern blotting and
      PCR-based amplification of various genes in filamentous fungi.

PMID- 28427935
TI  - The multi-faceted dynamics of HIV-1 transmission in Northern Alberta: A combined
      analysis of virus genetic and public health data.
AB  - Molecular epidemiology has become a key tool for tracking infectious disease
      epidemics. Here, the spread of the most prevalent HIV-1 subtypes in Northern
      Alberta, Canada, was characterized with a Bayesian phylogenetic approach using
      1146 HIV-1 pol sequences collected between 2007 and 2013 for routine clinical
      management purposes. Available patient metadata were qualitatively interpreted
      and correlated with onwards transmission using Fisher exact tests and logistic
      regression. Most infections were from subtypes A (n=36), B (n=815) and C (n=211).
      Africa is the dominant origin location for subtypes A and C while the subtype B
      epidemic was seeded from the USA and Middle America and, from the early 1990s
      onwards, mostly by interprovincial spread. Subtypes A (77.8%) and C (74.0%) were
      usually heterosexually transmitted and circulate predominantly among Blacks
      (61.1% and 85% respectively). Subtype B was mostly found among Caucasians (48.6%)
      and First Nations (36.8%), and its modes of transmission were stratified by
      ethnic origin. Compared to subtypes A (5.6%) and C (3.8-10.0%), a larger portion
      of subtype B patients were found within putative provincial transmission networks
      (20.3-29.5%), and this almost doubled when focusing on nationwide transmission
      clusters (37.9-57.5%). No clear association between cluster membership and
      particular patient characteristics was found. This study reveals complex and
      multi-faceted transmission dynamics of the HIV-1 epidemic in this otherwise low
      HIV prevalence population in Northern Alberta, Canada. These findings can aid
      public health planning.

PMID- 28427934
TI  - Cognitive subtypes of probable Alzheimer's disease robustly identified in four
      cohorts.
AB  - INTRODUCTION: Patients with Alzheimer's disease (AD) show heterogeneity in
      profile of cognitive impairment. We aimed to identify cognitive subtypes in four
      large AD cohorts using a data-driven clustering approach. METHODS: We included
      probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496),
      Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence
      Network (n = 521), and University of California, San Francisco (n = 589).
      Neuropsychological data were clustered using nonnegative matrix factorization. We
      explored clinical and neurobiological characteristics of identified clusters.
      RESULTS: In each cohort, a two-clusters solution best fitted the data (cophenetic
      correlation >0.9): one cluster was memory-impaired and the other relatively
      memory spared. Pooled analyses showed that the memory-spared clusters (29%-52% of
      patients) were younger, more often apolipoprotein E (APOE) E4 negative, and had
      more severe posterior atrophy compared with the memory-impaired clusters (all P <
      .05). CONCLUSIONS: We could identify two robust cognitive clusters in four
      independent large cohorts with distinct clinical characteristics.

PMID- 28427936
TI  - Molecular dissection of Caenorhabditis elegans ATP-binding cassette transporter
      protein HAF-4 to investigate its subcellular localization and dimerization.
AB  - Caenorhabditis elegans HAF-4 and HAF-9 are half-type ATP-binding cassette (ABC)
      transporter proteins, which are highly homologous to the human peptide
      transporter protein, transporter associated with antigen processing-like (TAPL,
      ABCB9). TAPL forms homodimers and localizes to lysosomes, whereas HAF-4 and HAF-9
      form heterodimers and localize to intestine-specific non-acidified organelles.
      Both TAPL and HAF-4/HAF-9 are predicted to have four amino-terminal transmembrane
      helices [transmembrane domain 0 (TMD0)] additional to the six transmembrane
      helices that form the canonical core domain of ABC transporters with a cytosolic
      ABC region. TAPL requires its amino-terminal domain for localization to
      lysosomes; however, molecular mechanisms underlying HAF-4 and HAF-9 localization
      to their target organelles had not been elucidated. Here, we demonstrate that the
      mechanisms underlying HAF-4 localization differ from those underlying TAPL
      localization. Using transgenic C. elegans expressing mutant HAF-4 proteins
      labeled with green fluorescent protein, we reveal that the TMD0 of HAF-4 was not
      sufficient for proper localization of the protein. The mutant HAF-4, which lacked
      TMD0, localized to intracellular organelles similarly to the wild-type protein
      and functioned normally in the biogenesis of its localizing organelles,
      indicating that the TMD0 of HAF-4 is dispensable for both its localization and
      function.

PMID- 28427937
TI  - Reactivity of anti-HNK-1 antibodies to branched O-mannose glycans associated with
      demyelination.
AB  - Human natural killer-1 (HNK-1) epitope, a highly-expressed glycan in the nervous
      system, is critical for normal synaptic plasticity and spatial learning. HNK-1
      epitope modifies N-glycans on several neural glycoproteins, and also modifies O
      mannosyl glycans. A branching enzyme for O-mannosyl glycans (GnT-IX, Core M2
      synthase) exhibits brain-specific expression, and the product core M2 glycans are
      also limited to the brain. In a previous study, we showed that cuprizone-induced
      demyelination increased HNK-1-capped core M2 glycan expression, while GnT-IX
      deficiency ameliorated demyelination, suggesting that these glycans could be
      useful diagnostic markers for demyelination status and act as therapeutic
      targets. Nevertheless, a lack of appropriate detection tools hampered further
      analysis of HNK-1-capped O-mannosyl glycans. In the present study, we
      chemoenzymatically synthesized HNK-1-capped core M2 glycans for antibody
      production, and confirmed that the resulting immune sera reacted with HNK-1
      capped core M2 glycans. We then examined several HNK-1-related antibodies,
      including the Cat-315 antibody, for reactions with HNK-1-capped core M2 glycans.
      Finally, we confirmed the increased HNK-1 epitope expression in demyelinated
      brains of cuprizone-fed mice.

PMID- 28427938
TI  - Ganoderma lucidum (Reishi) suppresses proliferation and migration of breast
      cancer cells via inhibiting Wnt/beta-catenin signaling.
AB  - The medical mushroom Ganoderma lucidum (Reishi), a traditional Chinese medicine,
      has exhibited a promising anti-cancer effect. However, the molecular mechanism of
      its action on cancer cells remains unclear. Aberrant activation of Wnt/beta
      catenin signaling pathway is the cause of many types of cancer, including breast
      cancer. Here we investigated the effect of Reishi on Wnt/beta-catenin signaling
      pathway and elucidated the molecular mechanism of its function in inhibiting
      breast cancer cells. We found that Reishi blocked Wnt/beta-catenin signaling
      through inhibiting the phosphorylation of Wnt co-receptor LRP6. In human (MDA-MB
      231) and mouse (4T1) breast cancer cell lines, Reishi significantly decreased the
      phosphorylation of LRP6 and suppressed Wnt3a-activated Wnt target gene Axin2
      expression. Administration of Reishi inhibited Wnt-induced hyper-proliferation of
      breast cancer cells and MDA-MB-231 cell migration. Our results provide evidence
      that Reishi suppresses breast cancer cell growth and migration through inhibiting
      Wnt/beta-catenin signaling, indicating that Reishi may be a potential natural
      inhibitor for breast cancer.

PMID- 28427939
TI  - NRAGE induces beta-catenin/Arm O-GlcNAcylation and negatively regulates Wnt
      signaling.
AB  - The Wnt pathway is crucial for animal development, as well as tumor formation.
      Understanding the regulation of Wnt signaling will help to elucidate the
      mechanism of the cell cycle, cell differentiation and tumorigenesis. It is
      generally accepted that in response to Wnt signals, beta-catenin accumulates in
      the cytoplasm and is imported into the nucleus where it recruits LEF/TCF
      transcription factors to activate the expression of target genes. In this study,
      we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein,
      markedly suppresses the expression of genes activated by the Wnt pathway.
      Consistent with this finding, loss of function of NRAGE by RNA interference
      (RNAi) activates the Wnt pathway. Moreover, NRAGE suppresses the induction of
      axis duplication by microinjected beta-catenin in Xenopus embryos. To our
      surprise, NRAGE induces nuclear localization of beta-catenin and increases its
      DNA binding ability. Further studies reveal that NRAGE leads to the modification
      of beta-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and
      failure of the association between beta-catenin/Arm and pygopus(pygo) protein,
      which is required for transcriptional activation of Wnt target genes. Therefore,
      our findings suggest a novel mechanism for regulating Wnt signaling.

PMID- 28427940
TI  - Characterization of the rax1 gene encoding a putative regulator of G protein
      signaling in Aspergillus fumigatus.
AB  - The filamentous fungus Aspergillus fumigatus is the major cause of life
      threatening invasive aspergillosis, and its small hydrophobic asexual spores
      (conidia) are the major infection agent. To better understand biology of A.
      fumigatus, we have characterized the rax1 gene encoding a putative regulator of G
      protein signaling (RGS). The deletion (Delta) of rax1 results in restricted
      colony growth and highly reduced number of conidia in A. fumigatus. Transcript
      levels of the three central activators of asexual development abaA, brlA, and
      wetA are significantly reduced in the Deltarax1 mutant. However, the Deltarax1
      conidia, but not vegetative cells, are specifically resistant against H2O2
      stress. The Deltarax1 conidia accumulate higher mRNA levels of sakA encoding a
      key MAP kinase for stress response. Moreover, the Deltarax1 conidia contain over
      five-fold amount of trehalose, an osmolyte and protein/membrane protectant.
      Transmission electron microscopy analyses indicate that the Deltarax1 conidia
      have the thicker melanized-outermost cell wall layer compared to those of wild
      type. In summary, Rax1 positively controls growth and development, and modulates
      intracellular trehalose amount, cell wall melanin levels in conidia, and spore
      resistance to H2O2.

PMID- 28427941
TI  - Elongation affinity, activation barrier, and stability of Abeta42
      oligomers/fibrils in physiological saline.
AB  - Amyloid-beta (Abeta) peptides, Abeta40 and the more neurotoxic Abeta42, have been
      the subject of many research efforts for Alzheimer's disease. In two recent
      independent investigations, the atomistic structure of Abeta42 fibril has been
      clearly established in the S-shaped conformation consisting of three beta-sheets
      stabilized by salt bridges formed between the Lys28 sidechain and the C-terminus
      of Ala42. This structure distinctively differs from the long-known structure of
      Abeta40 in the beta-hairpin shaped conformation consisting of two beta-sheets.
      Recent in silico investigations based on all-atom models have reached closer
      agreement with the in vitro measurements of Abeta40 thermodynamics. In this
      study, we present an in silico investigation of Abeta42 thermodynamics. Using the
      established force field parameters in seven sets of all-atom simulations, we
      examined the stability of small Abeta42 oligomers in physiological saline. We
      computed the elongation affinity of the S-shaped Abeta42 fibril, reaching
      agreement with the experimental data. We also estimated the Arrhenius activation
      barrier along the elongation pathway (from the disordered conformation of a free
      Abeta42 peptide to its S-shaped conformation on a fibril) that amounts to about
      16 kcal/mol, which is consistent with the experimental data. Based on these
      quantitative agreements, we conclude that aggregation of Abeta42 peptides into
      fibrils is thermodynamically slow without precipitation by extrinsic factors such
      as heparan sulfate proteoglycan and highlight the possibility to prevent Abeta42
      aggregation by eliminating some precipitation factors or by increasing
      competitive agents to capture and transport free Abeta42 peptides from the
      cerebrospinal fluid.

PMID- 28427942
TI  - Inhibitory effects of ethyl pyruvate on platelet aggregation and
      phosphatidylserine exposure.
AB  - Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies
      demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti
      coagulant effects. Inflammation and coagulation are closely interacted with
      platelet activation. However, it is unclear whether EP has anti-platelet effects.
      Therefore, we investigated the anti-platelet effect of EP in this study in vitro.
      We found that EP inhibited agonists induced platelets aggregation, ATP release
      and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited
      agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L
      expression. The underlying mechanism of action may involve the inhibition of
      platelet PI3K/Akt and Protein Kinase C (PKC) signaling pathways. Additionally, EP
      dose dependently inhibited platelet PS exposure induced by high concentration
      thrombin. Lactate dehydrogenase (LDH) activity assay and mice platelet count
      implied that EP may have no toxic effect on platelets. Therefore, we are the
      first to report that EP has potent anti-platelet activity and attenuates platelet
      PS exposure in vitro, suggesting that the inhibitory effects of EP on platelets
      may also play important roles in improvement of inflammation and coagulation
      disorder in related animal models.

PMID- 28427943
TI  - High density lipoprotein from coronary artery disease patients caused abnormal
      expression of long non-coding RNAs in vascular endothelial cells.
AB  - Increased evidence has showed that normal high density lipoprotein (HDL) could
      convert to dysfunctional HDL in diseases states including coronary artery disease
      (CAD), which regulated vascular endothelial cell function differently. Long non
      coding RNAs (lncRNAs) play an extensive role in various important biological
      processes including endothelial cell function. However, whether lncRNAs are
      involved in the regulation of HDL metabolism and HDL-induced changes of vascular
      endothelial function remains unclear. Cultured human umbilical vein endothelial
      cells (HUVECs) were treated with HDL from healthy subjects and patients with CAD
      and hypercholesterolemia for 24 h, then the cells were collected for lncRNA-Seq
      and the expressions of lncRNAs, genes and mRNAs were identified. The
      bioinformatic analysis was used to evaluate the relationship among lncRNAs,
      encoding genes and miRNAs. HDL from healthy subjects and patients with CAD and
      hypercholesterolemia leaded to different expressions of lncRNAs, genes and mRNAs,
      and further analysis suggested that the differentially expressed lncRNAs played
      an important role in the regulation of vascular endothelial function. Thus, HDL
      from patients with CAD and hypercholesterolemia could cause abnormal expression
      of lncRNAs in vascular endothelial cells to affect vascular function.

PMID- 28427944
TI  - Creating a Global Acute Care Surgery Fellowship to Meet International Need.
AB  - INTRODUCTION: Existing Acute Care Surgery (ACS) fellowships are positioned to
      develop well-trained surgeons with specific skills to facilitate improvements in
      care delivery in Global ACS. Many resident and fellowship programs offer clinical
      electives that expose trainees to operative experiences, exposing trainees to the
      needs in resource-challenged settings. However, most lack a focus on long-term
      development and research designed to enhance the country's local skills,
      capability, and capacity. The Global Acute Care Surgery (Global ACS) fellowship
      produces a surgeon who focuses on capacity building and systems development
      across the world. METHODS: At Vanderbilt University, the current American
      Association for the Surgery of Trauma-Acute Care Surgery (AAST-ACS) fellowship
      was adapted to create an academic Global Acute Care Surgery (Global ACS)
      fellowship. This fellowship specifically enhances fellowship trainee's skills in
      needs assessment and performing research to facilitate the development and
      implementation of trauma and acute care surgery systems in low- and middle income
      countries. This research will foster context-appropriate data, collected and
      based in low- and middle-income countries, to guide practice and policy. RESULTS
      AND CONCLUSION: Two fellows have completed the Global ACS fellowship at
      Vanderbilt University. The fellowship requirements, clinical skills, project
      development and overall goals are outlined within the article. Challenges,
      funding, and mentorship must also be addressed to develop a comprehensive
      fellowship. A sample two-year timeline is provided to complete the fellowship
      track and meet the defined goals. A structured global acute care surgery
      fellowship enables fellows to reduce the surgical burden of disease and
      contribute to surgical systems development at both local and international levels
      by creating meaningful research and developing sustainable change in LMIC
      countries.

PMID- 28427945
TI  - Accessories to SIV Control: T Cell Vaccination Shows Potential.

PMID- 28427946
TI  - Is an Early Age at Illness Onset in Schizophrenia Associated With Increased
      Genetic Susceptibility? Analysis of Data From the Nationwide Danish Twin
      Register.
AB  - BACKGROUND: Early age at illness onset has been viewed as an important liability
      marker for schizophrenia, which may be associated with an increased genetic
      vulnerability. A twin approach can be valuable, because it allows for the
      investigation of specific illness markers in individuals with a shared genetic
      background. METHODS: We linked nationwide registers to identify a cohort of twin
      pairs born in Denmark from 1951 to 2000 (N=31,524 pairs), where one or both twins
      had a diagnosis in the schizophrenia spectrum. We defined two groups consisting
      of; N=788 twin pairs (affected with schizophrenia spectrum) and a subsample of
      N=448 (affected with schizophrenia). Survival analysis was applied to investigate
      the effect of age at illness onset. FINDINGS: We found that early age at illness
      onset compared to later onset in the first diagnosed twin can be considered a
      major risk factor for developing schizophrenia in the second twin. Additionally,
      we found that the stronger genetic component in MZ twins compared to DZ twins is
      manifested in the proximity of assigned diagnosis within pairs. DISCUSSION: Early
      onset schizophrenia could be linked to a more severe genetic predisposition,
      indicating that age might be perceived as a clinical marker for genetic
      vulnerability for the illness.

PMID- 28427947
TI  - 4th Microbiome R&D and Business Collaboration Forum, and Probiotics Congress,
      April 3-4, 2017, Amsterdam, The Netherlands.

PMID- 28427948
TI  - Comprehensive Characterization of Humoral Correlates of Human Immunodeficiency
      Virus 1 Superinfection Acquisition in High-risk Kenyan Women.
AB  - HIV-1 superinfection, in which an infected individual acquires a second HIV-1
      infection from a different partner, is one of the only settings in which HIV
      acquisition occurs in the context of a pre-existing immune response to natural
      HIV infection. There is evidence that initial infection provides some protection
      from superinfection, particularly after 6months of initial infection, when
      development of broad immunity occurs. Comparison of the immune response of
      superinfected individuals at the time of superinfection acquisition to that of
      individuals who remain singly infected despite continued exposure can shed light
      on immune correlates of HIV acquisition to inform prophylactic vaccine design. We
      evaluated a panel of humoral immune responses in the largest published group of
      superinfected individuals (n=21), compared to a set of 3:1 matched singly
      infected controls from the same cohort. The immune functions studied included
      plasma neutralization, plasma and cervical antibody-dependent cellular
      cytotoxicity, and plasma IgG and IgA binding to a panel of 18 envelope antigens,
      including correlates of HIV acquisition in the RV144 vaccine trial, IgG binding
      to V1V2 and IgA binding to gp140. Association between each immune function and
      HIV superinfection was evaluated using conditional logistic regression. No
      significant associations were detected between any of the immune functions and
      superinfection acquisition. This study constitutes the most comprehensive and
      detailed characterization of multiple immune correlates of superinfection to
      date. The results suggest that immune responses not commonly measured in current
      HIV studies may be important in protection from HIV infection, and these or a
      more robust humoral response than that seen in naturally infected women may be
      needed for a protective vaccine.

PMID- 28427949
TI  - Parasitism finds many solutions to the same problems in red algae
      (Florideophyceae, Rhodophyta).
AB  - Parasitic red algae evolve from a common ancestor with their hosts, parasitizing
      cousins using familiar cellular mechanisms. They have independently evolved over
      one hundred times within the exclusively multicellular red algal class
      Florideophyceae. Reduced morphology, a lack of pigmentation, and direct cell-cell
      connections with their hosts are markers of red algal parasitism. With so many
      potential evolutionary pathways, red algal parasite diversity offers a unique
      test case to understand the earliest stages of this lifestyle transition.
      Molecular and morphological investigations led to the categorization of these
      parasites based on their relationship to their host. "Adelphoparasites" are
      phylogenetically close to their hosts, often infecting a sister species, whereas
      "alloparasites" are more distantly related to their hosts. The differentiation of
      these parasites, based on their phylogenetic relationship to their host, has
      resulted in a simplified classification of these parasites that may not reflect
      the many evolutionary pathways they take to arrive at a similar endpoint.
      Accordingly, many parasites fall into a gray area between adelphoparasite and
      alloparasite definitions, challenging the established features we use to classify
      them. Molecular phylogenetic research has been essential in identifying gaps in
      knowledge, but microscopy needs to be reincorporated in order to address red
      algal parasite developmental variation to establish a new paradigm. The joint
      utilization of molecular and microscopic methods will be critical in identifying
      the genomic and physiological traits of both nascent and well-established
      parasites.

PMID- 28427950
TI  - Response to a letter to the editor.

PMID- 28427951
TI  - Uncovering the immune responses of Apis mellifera ligustica larval gut to
      Ascosphaera apis infection utilizing transcriptome sequencing.
AB  - Honeybees are susceptible to a variety of diseases, including chalkbrood, which
      is capable of causing huge losses of both the number of bees and colony
      productivity. This research is designed to characterize the transcriptome
      profiles of Ascosphaera apis-treated and un-treated larval guts of Apis mellifera
      ligustica in an attempt to unravel the molecular mechanism underlying the immune
      responses of western honeybee larval guts to mycosis. In this study, 24, 296 and
      2157 genes were observed to be differentially expressed in A. apis-treated Apis
      mellifera (4-, 5- and 6-day-old) compared with un-treated larval guts. Moreover,
      the expression patterns of differentially expressed genes (DEGs) were examined
      via trend analysis, and subsequently, gene ontology analysis and KEGG pathway
      enrichment analysis were conducted for DEGs involved in up- and down-regulated
      profiles. Immunity-related pathways were selected for further analysis, and our
      results demonstrated that a total of 13 and 50 DEGs were annotated in the humoral
      immune-related and cellular immune-related pathways, respectively. Additionally,
      we observed that many DEGs up-regulated in treated guts were part of cellular
      immune pathways, such as the lysosome, ubiquitin mediated proteolysis, and insect
      hormone biosynthesis pathways and were induced by A. apis invasion. However, more
      down-regulated DEGs were restrained. Surprisingly, a majority of DEGs within the
      Toll-like receptor signaling pathway, and the MAPK signaling pathway were up
      regulated in treated guts, while all but two genes involved in the NF-kappaB
      signaling pathway were down-regulated, which suggested that most genes involved
      in humoral immune-related pathways were activated in response to the invasive
      fungal pathogen. This study's findings provide valuable information regarding the
      investigation of the molecular mechanism of immunity defenses of A. m. ligustica
      larval guts to infection with A. apis. Furthermore, these studies lay the
      groundwork for future researches on key genes controlling the susceptibility of
      A. m. ligustica larvae to chalkbrood.

PMID- 28427952
TI  - Anti-bullying Policies and Disparities in Bullying: A State-Level Analysis.
AB  - INTRODUCTION: Recent research suggests that anti-bullying laws may be effective
      in reducing risk of bullying victimization among youth, but no research has
      determined whether these laws are also effective in reducing disparities in
      bullying. The aim of this paper was to evaluate the effectiveness of anti
      bullying legislation in reducing disparities in sex- and weight-based bullying
      and cyberbullying victimization. METHODS: Data on anti-bullying legislation were
      obtained from the U.S. Department of Education, which commissioned a systematic
      review of 16 key components of state laws in 2011. States were also categorized
      based on whether their legislation enumerated protected groups and, if so, which
      groups were enumerated. These policy variables from 28 states were linked to
      individual-level data on bullying and cyberbullying victimization from students
      in 9th through 12th grade participating in the 2011 Youth Risk Behavior
      Surveillance System study (N=79,577). Analyses were conducted in 2016. RESULTS:
      There was an absence of any kind of moderating effect of anti-bullying
      legislation on weight-based disparities in bullying and cyberbullying
      victimization. Only state laws with high compliance to Department of Education
      enumeration guidelines were associated with lower sex-based disparities in
      bullying victimization. CONCLUSIONS: Anti-bullying policies were not associated
      with lower weight-based disparities in bullying and cyberbullying victimization
      among youth, and only one form of policies (high compliance to Department of
      Education enumeration guidelines) was associated with lower sex-based disparities
      in bullying victimization. Results therefore suggest that anti-bullying
      legislation requires further refinement to protect youth who are vulnerable to
      bullying victimization.

PMID- 28427953
TI  - Booster Seat Effectiveness Among Older Children: Evidence From Washington State.
AB  - INTRODUCTION: The American Academy of Pediatrics has recommended that children as
      old as 12 years use a booster seat when riding in motor vehicles, yet little is
      known about booster seat effectiveness when used by older children. This study
      estimated the association between booster use and injuries among children aged 8
      12 years who were involved in motor vehicle crashes. METHODS: Researchers
      analyzed data on all motor vehicle crashes involving children aged 8-12 years
      reported to the Washington State Department of Transportation from 2002 to 2015.
      Data were collected in 2015 and analyzed in 2016. Children who were in a booster
      seat were compared with children restrained by a seat belt alone. Logistic
      regression was used to adjust for potential confounders. RESULTS: In unadjusted
      models, booster use was associated with a 29% reduction in the odds of
      experiencing any injury versus riding in a seat belt alone (OR=0.709, 95%
      CI=0.675, 0.745). In models adjusted for potential confounders, booster use was
      associated with a 19% reduction in the odds of any injury relative to riding in a
      seat belt alone (OR=0.814, 95% CI=0.749, 0.884). The risk of experiencing an
      incapacitating/fatal injury was not associated with booster use. CONCLUSIONS:
      Children aged 8-12 years involved in a motor vehicle crash are less likely to be
      injured if in a booster than if restrained by a seat belt alone. Because only 10%
      of U.S. children aged 8-12 years use booster seats, policies encouraging their
      use could lead to fewer injuries.

PMID- 28427954
TI  - Colorectal Cancer Screening Initiation After Age 50 Years in an Organized
      Program.
AB  - INTRODUCTION: Recent studies report racial disparities among individuals in
      organized colorectal cancer (CRC) programs; however, there is a paucity of
      information on CRC screening utilization by race/ethnicity among newly age
      eligible adults in such programs. METHODS: This was a retrospective cohort study
      among Kaiser Permanente Northern California enrollees who turned age 50 years
      between 2007 and 2012 (N=138,799) and were served by a systemwide outreach and
      facilitated in-reach screening program based primarily on mailed fecal
      immunochemical tests to screening-eligible people. Kaplan-Meier and Cox model
      analyses were used to estimate differences in receipt of CRC screening in 2015
      2016. RESULTS: Cumulative probabilities of CRC screening within 1 and 2 years of
      subjects' 50th birthday were 51% and 73%, respectively. Relative to non-Hispanic
      whites, the likelihood of completing any CRC screening was similar in blacks
      (hazard ratio, 0.98; 95% CI=0.96, 1.00); 5% lower in Hispanics (hazard ratio,
      0.95; 95% CI=0.93, 0.96); and 13% higher in Asians (hazard ratio, 1.13; 95%
      CI=1.11, 1.15) in adjusted analyses. Fecal immunochemical testing was the most
      common screening modality, representing 86% of all screening initiations. Blacks
      and Hispanics had lower receipt of fecal immunochemical testing in adjusted
      analyses. CONCLUSIONS: CRC screening uptake was high among newly screening
      eligible adults in an organized CRC screening program, but Hispanics were less
      likely to initiate screening near age 50 years than non-Hispanic whites,
      suggesting that cultural and other individual-level barriers not addressed within
      the program likely contribute. Future studies examining the influences of
      culturally appropriate and targeted efforts for screening initiation are needed.

PMID- 28427955
TI  - Preventing Alcohol and Tobacco Exposed Pregnancies: CHOICES Plus in Primary Care.
AB  - INTRODUCTION: Alcohol and tobacco use are common among U.S. women, yet if used
      during pregnancy these substances present significant preventable risks to
      prenatal and perinatal health. Because use of alcohol and tobacco often continue
      into the first trimester and beyond, especially among women with unintended
      pregnancies, effective evidence-based approaches are needed to decrease these
      risk behaviors. This study was designed to test the efficacy of CHOICES Plus, a
      preconception intervention for reducing the risk of alcohol- and tobacco-exposed
      pregnancies (AEPs and TEPs). STUDY DESIGN: RCT with two intervention groups:
      CHOICES Plus (n=131) versus Brief Advice (n=130). Data collected April 2011 to
      October 2013. Data analysis finalized February 2016. SETTING/PARTICIPANTS:
      Settings were 12 primary care clinics in a large Texas public healthcare system.
      Participants were women who were non-sterile, non-pregnant, aged 18-44 years,
      drinking more than three drinks per day or more than seven drinks per week,
      sexually active, and not using effective contraception (N=261). Forty-five
      percent were smokers. INTERVENTION: Interventions were two CHOICES Plus sessions
      and a contraceptive visit or Brief Advice and referral to community resources.
      MAIN OUTCOME MEASURES: Primary outcomes were reduced risk of AEP and TEP through
      9-month follow-up. RESULTS: In intention-to-treat analyses across 9 months, the
      CHOICES Plus group was more likely than the Brief Advice group to reduce risk of
      AEP with an incidence rate ratio of 0.620 (95% CI=0.511, 0.757) and absolute risk
      reduction of -0.233 (95% CI=-0.239, -0.226). CHOICES Plus group members at risk
      for both exposures were more likely to reduce TEP risk (incidence rate ratio,
      0.597; 95% CI=0.424, 0.840 and absolute risk reduction, -0.233; 95% CI=-0.019, 
      0.521). CONCLUSIONS: CHOICES Plus significantly reduced AEP and TEP risk.
      Addressing these commonly co-occurring risk factors in a single preconception
      program proved both feasible and efficacious in a low-income primary care
      population. Intervening with women before they become pregnant could shift the
      focus in clinical practice from treatment of substance-exposed pregnancies to
      prevention of a costly public health concern. TRIAL REGISTRATION: This study is
      registered at clinicaltrials.gov NCT01032772.

PMID- 28427956
TI  - Curcumin/poly(2-methyl-2-oxazoline-b-tetrahydrofuran-b-2-methyl-2-oxazoline)
      formulation: An improved penetration and biological effect of curcumin in F508del
      CFTR cell lines.
AB  - Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize
      hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl
      2-oxazoline (MeOx) and tetrahydrofuran (THF) (MeOx6-THF19-MeOx6) (TBCP2) can
      solubilize curcumin (Cur) a very hydrophobic molecule exhibiting multiple
      therapeutic effects but whose insolubility and low stability in water is a major
      drawback for clinical applications. Here, we provide evidences by flow cytometry
      and confocal microscopy that Cur penetration in normal and DeltaF508-CFTR human
      airway epithelial cell lines is facilitated by TBCP2. When used on DeltaF508-CFTR
      cell lines, the Cur/TBCP2 formulation promotes the restoration of the expression
      of the CFTR protein in the plasma membrane. Furthermore, patch-clamp and MQAE
      fluorescence experiments show that this effect is associated with a correction of
      a Cl- selective current at the membrane surface of F508del-CFTR cells. The
      results show the great potential of the neutral amphiphilic triblock copolymer
      MeOx6-THF19-MeOx6 as carrier for curcumin in a Cystic Fibrosis context. We
      anticipate that other MeOxn-THFm-MeOxn copolymers could have similar behaviours
      for other highly insoluble therapeutic drugs or cosmetic active ingredients.

PMID- 28427957
TI  - PCR-based identification of Trypanosoma lewisi and Trypanosoma musculi using
      maxicircle kinetoplast DNA.
AB  - Trypanosoma lewisi, transmitted by rat fleas, is a widespread pathogen specific
      to rats with records of human infection cases. Its closely related species with
      global distribution, Trypanosoma musculi, is transmitted between mice by
      ingestion of infected fleas. These trypanosomes are of similar morphology, making
      it difficult to distinguish them by microscopy. In this study, we have developed
      a rapid, sensitive and reliable PCR method for the diagnosis of T. lewisi and T.
      musculi. The T. lewisi-specific amplicons were not produced by other Trypanosoma,
      such as T. musculi, T. brucei complex or T. cruzi, neither by an outgroup of
      Leishmania amazonensis. The detection limits of the three pairs of T. lewisi
      specific primers were 50ng, 1ng and 10ng of total DNA, respectively. The primers
      designed for T. musculi primers showed specifically that amplicon strictly in T.
      musculi and their detection limits were 10ng and 1ng of total DNA. To simplify
      the detection process, we managed to apply our method directly on tail blood
      samples without complicated DNA purification. In conclusion, PCR with our primers
      could be a highly sensitive, specific protocol to detect and distinguish T.
      lewisi and T. musculi from other trypanosomes.

PMID- 28427958
TI  - Micro-anatomical changes in major blood vessel caused by dengue virus (serotype
      2) infection.
AB  - Dengue virus (DENV) has emerged as a major economic concern in developing
      countries, with 2.5 billion people believed to be at risk. Vascular endothelial
      cells (ECs) lining the circulatory system from heart to end vessels perform
      crucial functions in the human body, by aiding gas exchange in lungs, gaseous,
      nutritional and its waste exchange in all tissues, including the blood brain
      barrier, filtration of fluid in the glomeruli, neutrophil recruitment, hormone
      trafficking, as well as maintenance of blood vessel tone and hemostasis. These
      functions can be deregulated during DENV infection. In this study, BALB/c mice
      infected with DENV serotype 2 were analyzed histologically for changes in major
      blood vessels in response to DENV infection. In the uninfected mouse model, blood
      vessels showed normal architecture with intact endothelial monolayer, tunica
      media, and tunica adventitia. In the infected mouse model, DENV distorted the
      endothelium lining and disturbed the smooth muscle, elastic laminae and their
      supporting tissues causing vascular structural disarrangement. This may explain
      the severe pathological illness in DENV-infected individuals. The overall DENV
      induced damages on the endothelial and it's supporting tissues and the
      dysregulated immune reactions initiated by the host were discussed.

PMID- 28427959
TI  - Beneficial effects of Heparin and l Arginine on dermonecrosis effect induced by
      Vipera lebetina venom: Involvement of NO in skin regeneration.
AB  - It is well known that snake venoms such as Viperidae caused severe local effects
      such as hemorrhage, myonecrosis and dermonecrosis which can lead to permanent
      tissue loss or the disability. The aim of this study is to evaluate the skin
      regeneration using heparin and l-arginine as well as the dermonecrotic effects
      induced by Vipera lebetina venom (VLV). To better understand the toxic effects
      induced by VLV and to prevent or treat these effects, we evaluate the local
      effects and the skin regeneration with or without drugs. The evaluation of NO as
      a marker of angiogenesis was also undertaken to understand its involvement in
      tissue wound healing and skin regeneration after envenomation. Obtained results
      showed that this venom is able to induce severe necrosis characterized by
      hemorrhage, hair follicles' destruction, glandular structure and increased of the
      thickness (acanthosis) in the epidermo-dermic junction. Inflammatory cells were
      also observed in the dermis. Pretreatment with heparin or L arginine seemed to
      decrease the induced dermonecrotic after one and two weeks improving the skin
      regeneration. The high level of NO could be involved in this regeneration, since
      it participates in the skin homeostatic functions' regulation and the maintenance
      of the skin protective barrier integrity against microorgansims. Nitric oxide
      plays also a key role in wound healing; it acts as a potent mitogenic stimulus to
      keratinocytes during skin repair and enhances the hair follicles and sebaceous
      gland structure that appeared after two weeks of treatment. Thus, these drugs
      could be used in therapeutic approach for dermonecrotic skin repair.

PMID- 28427960
TI  - Construct and expression of recombinant domains I/II of dengue virus- 2 and its
      efficacy to evaluate immune response in endemic area: Possible use in prognosis.
AB  - The envelope (E) protein from DENV, contain three functional and structural
      domains (DI, DII and DIII). Some studies suggest that neutralizing antibodies
      during natural DENV infection are predominantly against DI and DII, in contrast,
      low proportion of the antibodies were against DIII. Thus it is necessary to
      establish the proportion of human antibodies against DENV E protein that bind to
      DI and DII during the normal course of infection; as an indicator of the quality
      of the antibody response and to further design new vaccine candidates for DENV.
      The aim of this study was to express recombinant proteins harboring a 240
      aminoacid fragment of the E protein from DI and DII of DENV serotypes 2 and 3 in
      a eukaryotic S2 system. Further, we evaluate the antibodies against these
      antigens in samples from patients in acute phase of DF or DHF and compare it with
      the response of samples from healthy individuals from the same endemic areas and
      samples from healthy individuals from a non-endemic area (EA and NEA,
      respectively). These results suggest that the presence of antibodies against
      rEDI/DII might be used to identify patients at risk for severe disease.

PMID- 28427961
TI  - Evidence for enzootic circulation of Rift Valley fever virus among livestock in
      Cameroon.
AB  - Rift Valley fever virus (RVFV) is an arthropod-borne pathogen, causing serious
      epidemics in Africa and the Arabian Peninsula. In Cameroon serological data
      indicate the presence of RVFV, but active circulation of RVFV, causing clinical
      infections has not been proven yet. For this purpose we carried out a serological
      and molecular study on a total of 1953 randomly selected serum samples of small
      ruminants and cattle, which were collected in years 2013 and 2014 in Cameroon. In
      a first step, sera were screened serologically using a variety of assay formats
      to reveal RVFV specific antibodies. At the second stage, seropositive specimen
      were assessed for acute RVFV infections via IgM-specific ELISA and quantitative
      real-time RT-PCR. Our data show a significant difference in the antibody
      prevalence in cattle (13.5% [95% confidence interval: 11.4-15.7]) and small
      ruminants (3.4% [95% confidence interval: 2.3-4.7]), with indications for annual
      fluctuations and significant regional differences of seropositivity. One small
      ruminant and three bovines were eventually found to be positive in IgM ELISA and
      indications for viremia were found in one bovine by RVFV genome detection using
      quantitative real-time RT-PCR. The results of this study therefore corroborate
      the presence of acute RVFV-infection and its circulation in Cameroon.

PMID- 28427962
TI  - First report of a Rickettsia asembonensis related infecting fleas in Brazil.
AB  - The present study was performed in a non-endemic area for spotted fever (SF) in
      Imperatriz microregion, state of Maranhao, Brazil. Blood samples and
      ectoparasites were collected from 300 dogs of the Imperatriz microregion. Canine
      serum samples were tested individually by indirect immunofluorescence assay
      (IFA), using five Rickettsia isolates from Brazil. Antibodies reactive to at
      least one of the five species of Rickettsia were detected in 1.6% of the dogs
      (5/300). These sera were considered reactive to Rickettsia rickettsii and
      Rickettsia amblyommatis or very closely related species. The ticks (Acari:
      Ixodidae), identified as Rhipicephalus sanguineus sensu lato (Latreille), and the
      fleas, identified as Ctenocephalides felis, were tested by polymerase chain
      reaction (PCR) for detection of rickettsial DNA. More than 78% (83/106) of the C.
      felis fleas were found to be infected with Rickettsia species using gltA as
      rickettsial PCR targets, whereas no evidence of Rickettsia spp. was found in R.
      sanguineus s. l. Genetic analysis based on genes gltA, htrA and ompB showed that
      the detected strain, is most closely related to Rickettsia asembonensis (formerly
      Candidatus Rickettsia asemboensis). The present study is the first report of a R.
      asembonensis related infecting C. felis fleas in Brazil.

PMID- 28427963
TI  - Molecular investigation of piroplasma infection in white yaks (Bos grunniens) in
      Gansu province, China.
AB  - Piroplasmosis, including theileriosis and babesiosis, is a tick-borne
      haemoprotozoan disease responsible for huge economic losses to livestock
      industry. In China, the biology of piroplasms infective to cattle was well
      understood on the basis of pathogen isolations and molecular epidemiological
      surveys in the past few decades. But very limited information about the infection
      status of piroplasms in white yak (Bos grunniens), a semi-wild and endemic breed,
      has been recorded, so far. A total of 350 blood samples was collected from white
      yaks in 11 towns of Tianzhu Tibetan Autonomous County of Gansu province, China,
      during April to July 2015. The samples were tested using species-specific
      polymerase chain reaction (PCR) for Babesia bovis, B. bigemina, Theileria
      annulata, T. orientalis and T. sinensis. Positive samples were further sequenced
      and confirmed via sequence alignment. The results showed a high prevalence of
      piroplasms in the white yaks, 38.3%(134/350). Four Babesia/Theileria species were
      detected. The prevalences were 8.3% (B. bigemina), 7.7% (T. annulata), 9.7% (T.
      orientalis) and 26.0% (T. sinensis).No B. bovis-positive samples were detected.
      The single infections of B. bigemina, T. annulata, T. orientalis and T. sinensis
      were 2.3%, 2.6%, 5.1% and 16.9%, respectively. 11.4%(40/350) of these animals
      presented co-infections with 2 or 3 parasite species, in which 80.0% of co
      infection had T. sinensis infection and no co-infections with 4 parasite species
      was detected. This is the first report to investigate the Babesia/Theileria
      infection in white yaks using molecular diagnostic method, for detection of B.
      bigemina, T. annulata, T. sergenti and T. sinensis. The findings also offer novel
      insights into the role of white yaks in Babesia/Theileria epidemiology and
      valuable information for the control and management of piroplasmosis in white
      yaks.

PMID- 28427964
TI  - Scanning electron microscopic studies on antenna of Hemipyrellia ligurriens
      (Wiedemann, 1830) (Diptera: Calliphoridae)-A blow fly species of forensic
      importance.
AB  - Blow flies (Diptera: Calliphoridae) are one of the foremost organisms amongst
      forensic insects to colonize corpses shortly after death, thus are of immense
      importance in the domain of forensic entomology. The blow fly Hemipyrellia
      ligurriens (Wiedemann, 1830) (Diptera: Calliphoridae) is considered as a
      forensically important fly species globally and is also known for its medical and
      veterinary importance. In the present study, we report for the first time
      scanning electron microscopic studies on the morphology of sensilla of antenna of
      adult male and female of H. ligurriens is with profound importance in better
      understanding of the insect morphology from forensic entomological perspective,
      and also could aid in proper identification of the species from other calliphorid
      flies. The structural peculiarities observed in the (i) antenna of H. ligurriens
      with three segments- scape, pedicel and flagellum with dorso-laterally placed
      arista (ii) densely covered microtrichia and most abundant trichoid sensilla
      identified on the antenna (iii) observation of only one type of sensilla, chaetic
      sensilla (ChI) on the scape (iv) two types of chaetic sensilla (ChI and ChII) and
      styloconic sensilla on the pedicel (v) the flagellum with three types of sensilla
      trichoid, basiconic and coeloconic sensilla (vi) Basiconic sensilla with
      multiporous surfaces with characteristic olfactory function. Moderate sexual
      dimorphism in the width of the flagellum, the females with wider flagella than
      the males, bear significance to the fact that they bear more multi-porous
      sensilla than the males, thus suffice their need to detect oviposition sites.
      Significant difference was observed in the length and width of coeloconic
      sensilla between the two sexes, the females showed bigger coeloconic sensilla,
      suggesting their function in oviposition site detection and successful
      colonization in corpses.

PMID- 28427965
TI  - T1/ST2 deficient mice display protection against Leishmania infantum experimental
      infection.
AB  - T1/ST2 is a surface marker selectively expressed on type 2 helper (TH2) effector
      cells. As Leishmania infection in susceptible BALB/c mice have ascribed to a
      polarized TH2 response, this study aim to investigate the T1/ST2 (the receptor
      for IL-33), as a typical TH2 marker in the postulation that a shift towards a
      beneficial TH1 response would occur in the absence of ST2. For this, ST2 knockout
      (ST2-/-) and WT BALB/c mice were experimentally infected in the retro-orbital
      sinus with L. infantum. We showed that ST2-/- animals displayed better control of
      parasite burden in both spleen and liver tissues at different time points of
      chronic phases, and reduced spleenomegaly and hepatomegaly compared with the wild
      type (WT) mice. This was associated with increased in the IFN-gamma levels and
      expression by CD4+ and CD8+ lymphocytes. The inflammatory response encompasses
      transaminases (AST and ALT) releases and NO productions were remarkably lower in
      ST2-/- mice compared with WT. These data suggest that, ST2-/-) exert protection
      against L. infantum infection and probably shift the immune response toward TH1
      induction.

PMID- 28427966
TI  - IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) complicated by severe
      thrombocytopenia and thrombosis can pose significant treatment challenges. Use of
      alternative anticoagulants in this setting may increase bleeding risks,
      especially in patients who have a protracted disease course. Additional therapies
      are lacking in this severely affected patient population. METHODS: We describe
      three patients with HIT who had severe thromboembolism and prolonged
      thrombocytopenia refractory to standard treatment but who achieved an immediate
      and sustained response to IVIg therapy. The mechanism of action of IVIg was
      evaluated in these patients and in five additional patients with severe HIT. The
      impact of a common polymorphism (H/R 131) in the platelet IgG receptor
      FcgammaRIIa on IVIg-mediated inhibition of platelet activation was also examined.
      RESULTS: At levels attained in vivo, IVIg inhibits HIT antibody-mediated platelet
      activation. The constant domain of IgG (Fc) but not the antigen-binding portion
      (Fab) is required for this effect. Consistent with this finding, IVIg had no
      effect on HIT antibody binding in a solid-phase HIT immunoassay (platelet factor
      4 enzyme-linked immunoassay). The H/R131 polymorphism in FcgammaRIIa influences
      the susceptibility of platelets to IVIg treatment, with the HH131 genotype being
      most susceptible to IVIg-mediated inhibition of antibody-induced activation.
      However, at high doses of IVIg, activation of platelets of all FcgammaRIIa
      genotypes was significantly inhibited. All three patients did well on long-term
      anticoagulation therapy with direct oral anticoagulants. CONCLUSIONS: These
      studies suggest that IVIg treatment should be considered in patients with HIT who
      have severe disease that is refractory to standard therapies.

PMID- 28427968
TI  - The Global Burden of Atrial Fibrillation and Stroke: A Systematic Review of the
      Clinical Epidemiology of Atrial Fibrillation in Asia.
AB  - BACKGROUND: Our previous review reported great variability in the incidence and
      prevalence of atrial fibrillation (AF) in non-Western cohorts, especially from
      Asian countries; in recent years, epidemiologic studies on AF have been
      increasingly reported from Asia. METHODS: The goal of this updated systematic
      review was to present the current knowledge base of AF epidemiology in Asian
      countries since our previous review. We also explored AF incidence and the risk
      of stroke in AF by using a meta-analysis, with I2 testing the heterogeneity.
      Third, "real-world" antithrombotic drug use for ischemic stroke (IS) prevention
      associated with AF was studied. RESULTS: A total of 58 articles from eight
      countries in Asia were included in the analysis. The summary annual incidence of
      AF was 5.38 (95% CI, 4.53-6.24; I2 = 99.5%; n = 10) per 1,000 person-years, and
      the IS annual risk in AF was 3.0% (1.60%-4.95%; I2 = 99.8%; n = 8) when meta
      analysis was performed on hospital- and community-based studies. Hospital- and
      community-based AF prevalence ranged from 0.37% to 3.56% and 2.8% to 15.8%,
      respectively. IS prevalence in AF ranged from 1.9% to 6.0% and 0.36% to 28.3% in
      community- and hospital-based studies. Warfarin use in Chinese subjects is
      relatively low (1.0%-4.1%) compared with Japanese subjects (49.1%-70.0%) in
      community-based studies. The rate of warfarin use was < 50% in hospital-based
      studies. CONCLUSIONS: The incidence and prevalence of AF have increased in recent
      years, although great variability still exists in Asian countries. Variability in
      annual IS risk in patients with AF was apparent between hospital- and community
      based studies. However, the rate of warfarin use was < 50% in hospital studies
      from Asian countries.

PMID- 28427967
TI  - Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.
AB  - Pulmonary disease remains a primary source of morbidity and mortality in persons
      living with HIV (PLWH), although the advent of potent combination antiretroviral
      therapy has resulted in a shift from predominantly infectious to noninfectious
      pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension,
      and lung cancer even in the era of combination antiretroviral therapy. The
      underlying mechanisms of this are incompletely understood, but recent research in
      both human and animal models suggests that oxidative stress, expression of matrix
      metalloproteinases, and genetic instability may result in lung damage, which
      predisposes PLWH to these conditions. Some of the factors that drive these
      processes include tobacco and other substance use, direct HIV infection and
      expression of specific HIV proteins, inflammation, and shifts in the microbiome
      toward pathogenic and opportunistic organisms. Further studies are needed to
      understand the relative importance of these factors to the development of lung
      disease in PLWH.

PMID- 28427969
TI  - Hyperbaric Oxygen Therapy Is Associated With Lower Short- and Long-Term Mortality
      in Patients With Carbon Monoxide Poisoning.
AB  - BACKGROUND: To date, there has been no consensus about the effect of hyperbaric
      oxygen therapy (HBOT) on the mortality of patients with carbon monoxide poisoning
      (COP). This retrospective nationwide population-based cohort study from Taiwan
      was conducted to clarify this issue. METHODS: Using the Nationwide Poisoning
      Database, we identified 25,737 patients with COP diagnosed between 1999 and 2012,
      including 7,278 patients who received HBOT and 18,459 patients who did not. The
      mortality risks of the two cohorts were compared, including overall mortality,
      and stratified analyses by age, sex, underlying comorbidities, monthly income,
      suicide attempt, drug poisoning, acute respiratory failure, and follow-up until
      2013 were conducted. We also tried to identify independent mortality predictors
      and evaluated their effects. RESULTS: Patients who received HBOT had a lower
      mortality rate compared with patients who did not (adjusted hazard ratio [AHR],
      0.74; 95% CI, 0.67-0.81) after adjusting for age, sex, underlying comorbidities,
      monthly income, and concomitant conditions, especially in patients younger than
      20 years (AHR, 0.45; 95% CI, 0.26-0.80) and those with acute respiratory failure
      (AHR, 0.43; 95% CI, 0.35-0.53). The lower mortality rate was noted for a period
      of 4 years after treatment of the COP. Patients who received two or more sessions
      of HBOT had a lower mortality rate than did those who received HBOT only once.
      Older age, male sex, low monthly income, diabetes, malignancy, stroke,
      alcoholism, mental disorders, suicide attempts, and acute respiratory failure
      were also independent mortality predictors. CONCLUSIONS: HBOT was associated with
      a lower mortality rate in patients with COP, especially in those who were younger
      than 20 years and those with acute respiratory failure. The results provide
      important references for decision-making in the treatment of COP.

PMID- 28427970
TI  - Structured Evaluation of Glioma Patients by an Occupational Therapist-Is Our
      Clinical Examination Enough?
AB  - BACKGROUND: Preservation of neurologic function is mandatory when offering a
      surgical intervention to patients with low-grade gliomas (LGGs), given that the
      goal of any treatment is the patient's return to their normal everyday life.
      OBJECTIVE: To determine whether a structured evaluation by an occupational
      therapist can reveal deficits that might be overseen in routine clinical
      examination of patients with a surgically treated LGG. METHODS: A total of 20
      patients with radiographically suspected LGG were examined in a standardized
      fashion at 3 stages: preoperatively, postoperatively, and 3 months thereafter.
      Results were analyzed descriptively. RESULTS: A total of 19 patients (95%) showed
      no postoperative motor deficit; one suffered from akinesia due to supplementary
      motor area involvement and demonstrated a transient deficit with manifestation on
      the first postoperative day. Patients with eloquent LGGs, involving speech (n =
      6, 30%), exhibited different transient speech disturbances according to the
      location of the lesion. Structured testing revealed a postoperative worsening of
      movement mirroring (upper extremity) and finger discrimination (sensory) in 5 of
      20 patients (25%). Force meter evaluation of the upper extremity was decreased
      significantly postoperatively for the affected hemisphere, even though motor
      deficits were absent in most patients. The action research arm test detected
      deterioration in more than one half of the patients postoperatively. Patients
      recovered from these deficits within the first 3 months. CONCLUSIONS: Routine
      clinical examination and neuropsychological evaluation fail to detect mild
      deficits in sensory function, reactivity, and apraxia, which may have a serious
      impact on patients' ability to return to their normal lives and work.

PMID- 28427971
TI  - Extent of Resection in Glioma-A Review of the Cutting Edge.
AB  - Modern glioma surgery has evolved from the principal belief that safe, maximal
      tumor resection improves symptom management, quality of life, progression-free
      survival, and overall survival in both low-grade and high-grade glioma. However,
      in the absence of level I data, the overwhelming support for this idea is derived
      largely from retrospective series. As a result, the influence of increasing
      extent of resection and reducing tumor burden on the efficacy of postoperative
      chemotherapy and radiotherapy, and survival, remains inadequately defined. This
      situation is particularly true because gliomas represent a widely heterogeneous
      group of tumors with varying behaviors and prognoses rooted in their complex
      molecular profile. The neurosurgical community has made a large effort to define
      the clinical benefits of maximizing tumor resection, with particular attention
      paid to the ever-evolving understanding of glioma molecular heterogeneity.
      Important new technologies have been developed concurrently to mitigate
      neurologic risks related to the pursuit of maximizing extent of resection. These
      advances reflect the modern goal of glioma surgery to find the optimal balance
      between tumor removal and neurologic compromise. We review the current literature
      supporting safe, maximal resection for gliomas.

PMID- 28427972
TI  - Endovascular Treatment of Complex Distal Posterior Cerebral Artery Aneurysms with
      the Pipeline Embolization Device.
AB  - OBJECTIVE: To assess the safety and efficacy of the Pipeline Embolization Device
      (PED) for endovascular treatment of complex, distal posterior cerebral artery
      (PCA) aneurysms. METHODS: We conducted a retrospective review of patients who
      underwent endovascular treatment of complex PCA aneurysms with PED from November
      2012 to December 2015. A total of 4 patients were identified and treated. Twelve
      month angiographic and clinical follow-up was available for all patients.
      RESULTS: Mean aneurysm size (largest diameter) was 10.0 mm, and all aneurysms
      originated at the P2 segment or beyond. Technical success was achieved in all
      patients. All patients were treated with a single PED; adjunctive intrasaccular
      coil was also placed in one patient. All patients achieved a favorable
      postprocedural outcome (modified Rankin Scale score = 0) with no new neurologic
      deficits. No patients experienced neurologic complications or perforator
      infarction, and presenting symptoms resolved in all patients. Follow-up cerebral
      angiography at 12 months in 3 patients showed complete occlusion (Raymond-Roy
      Occlusion Classification class 1) and minimal residual aneurysm filling (Raymond
      Roy Occlusion Classification class 2) in 1 patient. A small degree of focal
      stenosis was present in 2 patients within the PED at 12-month follow-up that was
      associated with mild decrease in flow within the distal PCA branches.
      CONCLUSIONS: PED use provides a practical and viable treatment option for
      complex, distal PCA aneurysms. Based on our limited institutional experience, PED
      use for treatment of complex, distal PCA aneurysms in select patients appears
      safe and effective.

PMID- 28427973
TI  - Ultra-High Field Template-Assisted Target Selection for Deep Brain Stimulation
      Surgery.
AB  - BACKGROUND: Template and atlas guidance are fundamental aspects of stereotactic
      neurosurgery. The recent availability of ultra-high field (7 Tesla) magnetic
      resonance imaging has enabled in vivo visualization at the submillimeter scale.
      In this Doing More with Less article, we describe our experiences with
      integrating ultra-high field template data into the clinical workflow to assist
      with target selection in deep brain stimulation (DBS) surgical planning. METHODS:
      The creation of a high-resolution 7T template is described, generated from group
      data acquired at our center. A computational workflow was developed for spatially
      aligning the 7T template with standard clinical data and furthermore, integrating
      the derived imaging volumes into the surgical planning workstation. RESULTS: We
      demonstrate that our methodology can be effective for assisting with target
      selection in 2 cases: unilateral internal pallidum DBS for painful dystonia and
      bilateral subthalamic nucleus DBS for Parkinson's disease. CONCLUSIONS: In this
      article, we have described a workflow for the integration of high-resolution in
      vivo ultra-high field templates into the surgical navigation system as a means to
      assist with DBS planning. The method does not require any additional cost or time
      to the patient. Future work will include prospectively evaluating different
      templates and their impact on target selection.

PMID- 28427974
TI  - Factors Predicting Spontaneous Thrombosis of Aggressive Cranial Dural
      Arteriovenous Fistulas.
AB  - BACKGROUND: Dural arteriovenous fistula (DAVF) with cortical venous drainage is
      known to be aggressive in clinical course and is usually managed promptly.
      Spontaneous resolution of DAVF is a rare phenomenon and usually occurs in benign
      fistulas. Spontaneous thrombosis of aggressive DAVF is an extremely rare
      occurrence. The present study aimed to identify the incidence and factors
      determining spontaneous resolution of aggressive DAVF. METHODS: All patients
      presenting to our institution with suspected DAVF during the study period (July
      2013 to December 2015) were prospectively enrolled into a database. Different
      clinical, demographic, and angiographic factors were compared between the control
      cohort who showed spontaneous resolution and the interventional cohort who
      underwent endovascular intervention for definite cure. The potential determinants
      reported in the literature were also included in this detailed analysis. RESULTS:
      Thirty-two patients were included in the final analysis. Five patients (15.7%)
      showed spontaneous resolution in the follow-up period while awaiting definitive
      treatment. Univariate analysis showed 3 variables (DAVF architecture, thrombosis
      of draining vein, and transit time) to be statistically significant (P < 0.05).
      However, multivariate logistic regression analysis showed that only sparse
      fistulous network was significantly associated with acceptable outcome of
      spontaneous disappearance of DAVF. CONCLUSIONS: Spontaneous thrombosis of
      aggressive DAVF is a known phenomenon in the natural evolution of cerebral dural
      arteriovenous malformation. DAVF architecture could categorize this particular
      subset of DAVF, which had an overall good prognosis. Further observations in
      large multi-institutional cohorts are needed to validate this finding and to
      ascertain other factors precipitating this outcome.

PMID- 28427975
TI  - Surgical Management of Vertex Epidural Hematoma: Technical Case Report and
      Literature Review.
AB  - BACKGROUND: Vertex epidural hematoma (VEH) is an uncommon presentation of extra
      axial hematomas. It can represent a surgical dilemma regarding when and how to
      operate, particularly considering the potential implication of the superior
      sagittal sinus (SSS). OBJECTIVE: Here, we illustrate the surgical technique for
      VEH as well as a review of the existing literature. METHODS: A 60-year-old man
      sustained a ground-level fall resulting in complete diastasis of the sagittal
      suture with underlying large VEH causing significant mass effect on the SSS and
      bihemispheric convexities. Twenty-four hours later, the patient deteriorated,
      with decreased level of alertness and worsening asymmetric paresis on his lower
      extremities. He subsequently underwent surgical evacuation of the hematoma,
      decompression of the SSS, and fracture repair. A modified bicoronal approach,
      with bilateral parasagittal craniotomies, was performed. A central island of bone
      was left intact to spare the diastatic fracture from the craniotomies. This was
      done to ensure a stable anchor point for tacking-up the underlying displaced dura
      and SSS. The central bone prevents extensive bleeding from the diastatic fracture
      and eliminates the risk of further blood reaccumulation and tearing of a possible
      injured sinus during bone flap elevation. RESULTS: The technique performed
      allowed us to evacuate completely the hematoma while preserving the SSS and
      repairing the sagittal suture to avoid further bleeding. Complete neurologic
      recovery of the patient occurred after VEH evacuation. CONCLUSIONS: Because of
      its rare nature, VEH represents a surgical challenge. Because neurosurgeons
      encounter this condition relatively infrequently, literature regarding the
      medical and surgical management of this entity is warranted.

PMID- 28427976
TI  - Posterior Multilevel Instrumentation of the Lower Cervical Spine: Is Bridging the
      Cervicothoracic Junction Necessary?
AB  - BACKGROUND: Multisegmental cervical instrumentations ending at the
      cervicothoracic junction may lead to significant adjacent segment degeneration.
      The purpose of this study was to compare the extent of sequential pathologies in
      the lower adjacent segment between patient groups with a primarily cervical
      instrumentation ending at C7 versus an instrumentation including the
      cervicothoracic junction ending at T1 or T2. METHODS: A retrospective analysis of
      98 consecutive patients with multisegmental posterior cervical fusion surgery
      ending either at C7 or at T1 or T2 was performed. Radiographic parameters of
      degeneration at the adjacent segment below the instrumentation were determined
      postoperatively and at follow-up (FU), and the need for secondary interventions
      was documented. RESULTS: A total of 74 patients had a FU of at least 6 months
      (C7: n = 58, age 63 +/- 11 years, FU 36 +/- 26 months; T1/T2: n = 16, age 65 +/-
      13 years, FU 37 +/- 21 months). There were no significant differences between the
      C7 and T1/T2 groups with regard to the change in kyphosis angle (P = 0.162), disc
      height (P = 0.204), or disc degeneration according to the Mimura grading system
      (P = 0.718). Secondary interventions due to adjacent segmental pathology or
      implant failure were necessary in 18 of 58 (31%) of the C7 cases and in 1 of 16
      (6.3%) of the T1/T2 cases (P = 0.038). CONCLUSIONS: Patients with multisegmental
      posterior cervical fusions ending at C7 showed a greater rate of clinically
      symptomatic pathologies at the adjacent level below the instrumentation. On the
      basis of our data and with its limitations in mind, one may consider to bridge
      the cervicothoracic junction and to end the instrumentation at T1 or T2 in those
      cases.

PMID- 28427977
TI  - Decompressive Craniectomy in Spontaneous Intracerebral Hemorrhage: A Case-Control
      Study.
AB  - BACKGROUND: Decompressive craniectomy is performed to relieve intracranial
      pressure as an emergency procedure. There is no large study to systematically
      evaluate the benefit of decompressive craniectomy versus best medical therapy.
      This study evaluates the survival and long-term functional outcomes of
      decompressive craniectomy for spontaneous intracranial hemorrhage. METHODS: A
      total of 54 eligible patients with spontaneous supratentorial hemorrhage (median
      age, 55 years; interquartile range, 47-64 years) who underwent decompressive
      craniectomy were retrospectively matched to 72 patients managed with best medical
      treatment (median age, 58 years; interquartile range, 32-74 years). Glasgow
      Outcome Scale (GOS) scores were dichotomized into favorable and unfavorable
      outcomes. Survival and functional outcomes were analyzed at discharge, 3, 6, and
      12 months. RESULTS: Survival in the craniectomy group was significantly higher
      compared with the medical treatment group at 30 days, 6, and 12 months (76%, 70%,
      and 70% vs. 60%, 57%, and 52% respectively; all P <= 0.05). There was no
      difference in functional outcomes at discharge, 3, 6, or 12 months after
      hemorrhage (all P > 0.05). Decompressive craniectomy was associated with longer
      hospital stay (median of 30 days vs. 7 days in the control group; P < 0.001).
      Hospital adverse events were more frequent in the craniectomy group than in the
      control group (76% vs. 33%; P < 0.001), the commonest adverse events being
      pneumonia and urinary tract infections. CONCLUSIONS: We showed that decompressive
      craniectomy significantly improved survival compared with medical treatment with
      lasting benefits. This improvement came at a cost of increased length of hospital
      stay and related adverse events. There was no improvement in functional outcome.

PMID- 28427979
TI  - A New Type of Spinal Epidural Arteriovenous Fistulas Causes Spinal Epidural
      Hemorrhage: An Analysis of Five Cases and Natural History Consideration.
AB  - BACKGROUND: Spinal epidural arteriovenous fistulas (SEDAVFs) are peculiar and
      poorly understood lesions with a poorly understood natural history. They usually
      are subclassified into 2 types according to their drainage components. This study
      aimed to describe a new type of SEDAVFs that is featured with a unique drainage
      pattern and present our natural history hypothesis of SEDAVFs. METHODS: Five
      SEDAVF cases of the new type were reviewed retrospectively from a high case
      volume spinal vascular malformation database. The clinical manifestations,
      neuroradiologic findings, angioarchitecture, treatment strategies, and clinical
      outcomes were assessed. RESULTS: All patients presented with spontaneous spinal
      epidural hematoma, and 2 of them exhibited rebleeding. The median age at the
      initial episode was 20 years. Spinal digital subtraction angiography revealed
      slow-flow epidural fistulas drained by spinal epidural venous plexus without
      intradural drainage or engorged venous pouches in all 5 patients. Three patients
      underwent microsurgical treatment. The outcomes of all of the patients were
      favorable. CONCLUSIONS: Our study reported a special type of hemorrhagic SEDAVF
      without an intradural drainage component or epidural mass effect. The key
      diagnostic clue was early opacification of spinal epidural venous plexus on
      spinal angiogram. We believe SEDAVFs may form at an early age and gradually
      develop with time. Different types of SEDAVFs may represent different developing
      stages of one disease, and our type may represent the early stage of SEDAVFs.

PMID- 28427978
TI  - Prevalence of Ponticulus Posticus on Lateral Cephalometric Radiographs, its
      Association with Cervicogenic Headache and a Review of Literature.
AB  - OBJECTIVES: The aim of this study was to calculate the prevalence of ponticulus
      posticus (a small bony bridge on the dorsal aspect of the atlas on lateral
      digital cephalometric radiographs) and classify it into a complete ring or an
      incomplete ring. The study also investigated its association with the presence or
      absence of cervicogenic headache in the examined population; a literature review
      of ponticulus posticus is also presented. METHODS: The presence and types of
      ponticuli posticus were investigated on 500 digital lateral cephalograms and the
      same patients were questioned for a history of cervicogenic headache. RESULTS: In
      500 patients, 79 ponticulus posticus (34 complete and 45 incomplete) were
      identified on the lateral cephalograms; therefore, the prevalence was 15.8%. The
      distribution of the type of ponticulus posticus was 13.1% in males and 17.9% in
      females in the studied sample. The overall prevalence of cervicogenic headache
      was 6% in the studied sample with a significant association between cervicogenic
      headache and type of ponticulus posticus. CONCLUSIONS: The study shows that
      ponticulus posticus is not a rare finding and its association with unexplainable
      headache, neck pain, and other symptoms as well as its importance and
      implications during management of cervical spine surgical procedures, especially
      those requiring lateral mass screw placements in the atlas, imply that
      radiologists and dentists in general should closely inspect the vertebral region
      on a lateral cephalogram.

PMID- 28427980
TI  - Comparative Study Between Cobalt Chrome and Titanium Alloy Rods for Multilevel
      Spinal Fusion: Proximal Junctional Kyphosis More Frequently Occurred in Patients
      Having Cobalt Chrome Rods.
AB  - BACKGROUND: The use of titanium alloy (Ti) rods is frequently associated with rod
      fracture after spinal fixation. To address this issue, cobalt chrome (CoCr) rods,
      which are advantageous because of their greater strength and resistance to
      fatigue relative to Ti rods, have been introduced. The purpose of the present
      study was to compare radiographic outcomes after the use of Ti versus CoCr rods
      in a matched cohort of patients undergoing posterior spinal fusion for treatment
      of spinal instability. METHODS: We retrospectively reviewed data from patients
      who had undergone spinal fusion involving more than 3 levels at a single
      institution between 2004 and 2015. Patients were matched for age, diagnosis, 3
      column osteotomy, levels fused, and T score. Fifty patients with Ti rods were
      identified and appropriately matched to 50 consecutive patients with CoCr rods.
      RESULTS: The distributions of age at surgery, sex, diagnosis, 3-column osteotomy,
      levels fused, number of patients with previous surgical procedures, and T score
      did not significantly differ between the 2 groups. However, there were
      significant differences in length of follow-up (CoCr, 25.0 vs. Ti, 28.5 months; P
      < 0.001), fusion rate (CoCr, 45 [90%] vs. Ti, 33 [66%]; P = 0.004), occurrence of
      rod breakage (CoCr, 0 vs. T, 8 [16%]; P = 0.006), and junctional kyphosis (CoCr,
      24 [46%] vs. Ti, 9 [18%]; P = 0.003). CONCLUSIONS: Our findings indicate that the
      use of CoCr rods is effective in ensuring stability of the posterior spinal
      construct and accomplishment of spinal fusion. Furthermore, our results indicate
      that junctional kyphosis may occur more frequently in CoCr systems than in Ti
      systems.

PMID- 28427981
TI  - Ultrastructure of Pericystic or Intracystic Blood Vessels in Epidermoid Cysts-A
      Transmission Electron Microscopy Study: Laboratory Investigation.
AB  - OBJECTIVES: Recently, we reported a tendency toward spontaneous hemorrhage in
      both the preoperative and postoperative periods in patients with intracranial
      epidermoid cyst (EC). According to our experience, this tendency for spontaneous
      hemorrhage was partly caused by the pathologic blood vessels adjacent to the EC.
      This study was designed to testify this hypothesis. METHODS: Twenty-three
      removable pericystic or intracystic blood vessels from 17 patients with EC were
      collected during surgery and were then examined by transmission electron
      microscopy. The microvascular structure in gliomas was chosen as the control.
      RESULTS: Under electron microscopy, variant pathologic changes of vessels were
      found in all patients with EC. In the tunicae intima, we found vacuolization,
      apoptosis, necrosis, and intralumenal protrusion of endothelial cells, as well as
      swollen basement and highly flexed and discontinued elastic plate. In the tunicae
      media, vacuolization and swollen mitochondria were found in muscular cells. In
      the tunicae adventitia, extravascular erythrocytes, edema or apoptosis of
      pericytes, collagen predominance, and inflammatory cell infiltration and
      destruction were found. Neuron denature and necrosis were found in the peripheral
      brain tissue. In the microvascular structure of 5 glioma specimens, we found
      enlargement and hyperplasia of endothelial cells, swollen basement membrane,
      swollen pericytes, and astrocytic hyperplasia and neuron denature in adjacent
      brain tissues. CONCLUSIONS: Our findings provide strong evidence for the
      hypothesis that intracystic or pericystic vascular degeneration or destruction
      accounts for the spontaneous hemorrhage tendency before and after surgical
      resection of ECs.

PMID- 28427982
TI  - Preoperative Evaluation of Sellar and Parasellar Macrolesions by
      [18F]Fluorodeoxyglucose Positron Emission Tomography.
AB  - OBJECTIVE: Various diseases can occur in the sellar and suprasellar regions. The
      potential of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) for
      the preoperative evaluation of sellar and parasellar lesions was investigated.
      METHODS: A total of 49 patients aged 8-82 years with sellar and parasellar
      macroscopic lesions (>=10 mm) underwent FDG PET. Twenty-two patients had
      pituitary adenomas, including 14 nonfunctioning and 8 growth hormone-secreting
      adenomas. Eleven patients had craniopharyngiomas, including 5 adamantinomatous
      and 6 squamous-papillary types. Eight patients had chordoma, 4 had meningioma,
      and 4 had a Rathke cleft cyst. The maximum standardized uptake value (SUVmax),
      and the ratio of the SUVmax in the tumor to the mean standardized uptake value in
      the normal cortex (T/N ratio) or in the normal white matter (T/W ratio) were
      calculated. The relationships between SUVmax, T/N ratio, and T/W ratio, and
      lesion disease were evaluated. RESULTS: Uptakes of FDG, including SUVmax, T/N
      ratio, and T/W ratio, were lower in chordoma and Rathke cleft cyst compared with
      pituitary adenoma. SUVmax, T/N ratio, and T/W ratio of nonfunctioning adenoma
      were significantly higher than those of growth hormone-secreting adenoma. SUVmax,
      T/N ratio, and T/W ratio of squamous-papillary type were significantly higher
      than those of the adamantinomatous type of craniopharyngioma. CONCLUSIONS: FDG
      PET is useful for the preoperative diagnosis of sellar and parasellar
      macrolesions. High uptake in nonfunctioning pituitary adenoma, and low uptake in
      chordoma are significant. The difference in FDG uptake dependent on the
      histologic subtype may be related to the specific genetics of the
      craniopharyngioma subtype.

PMID- 28427983
TI  - Effect of Headache on the Pathologic Findings of Unruptured Cerebral Saccular
      Aneurysms.
AB  - BACKGROUND: Some patients with aneurysm exhibit warning headaches without minor
      bleeding, and this could be caused by stretching of the aneurysm wall. Recently,
      our pathologic study observed subintimal fibrin deposition in a majority of the
      ruptured aneurysms. However, these findings also were observed in some unruptured
      aneurysms. In this report, 2 unruptured aneurysms exhibited subintimal fibrin,
      and interestingly, one of the patients experienced severe headache within 1 month
      before neuroimaging. OBJECTIVE: We performed pathologic analysis of unruptured
      aneurysms and collected their various clinical variables, including severe
      headache, to clarify the clinical characteristics of "dangerous" unruptured
      aneurysms. METHODS: This study included unruptured saccular aneurysm samples (n =
      17) that were resected after clipping. We compared the differences in clinical
      variables, including warning headache, between aneurysms with and without fibrin
      deposition. RESULTS: Fibrin deposition was present in the subintimal layer in 4
      patients and in the periouter membrane in 4 patients. Three of the 4 former
      patients experienced warning headaches, and one presented aneurysm growth. Of the
      latter 4 patients, one exhibited aneurysm growth, whereas the others presented
      with relatively large aneurysms. In the remaining 9 aneurysms without fibrin
      deposition, monocyte infiltration was observed in one, all aneurysms were small,
      and no patients experienced warning headaches or aneurysm growth. CONCLUSIONS:
      Subintimal fibrin deposition is observed frequently in patients with aneurysm
      with warning headaches. These pathologic findings are clinically inspiring and
      may suggest that these aneurysms exhibit rapid stretching by newly formed
      aneurysms, which can result in rupture at an early stage.

PMID- 28427984
TI  - Effect of Baseline Characteristics on the Outcome of Stent Retriever-Based
      Thrombectomy in Acute Basilar Artery Occlusions: A Single-Center Experience and
      Pooled Data Analysis.
AB  - OBJECTIVES: To explore the association of baseline characteristics and the
      outcome of patients with acute basilar artery occlusion (BAO) after stent
      retriever-based thrombectomy (SRT). METHODS: Clinical and imaging information of
      consecutive SRT-treated patients with BAO from a comprehensive stroke center and
      up-to-date literature were reviewed respectively. The impact of baseline
      variables toward favorable outcome was evaluated using subgroup analysis and odds
      ratio (OR) extracted from published data together with single-center records
      using pooled analysis. RESULTS: Nineteen cases from our center and 15 published
      studies involving 487 cases were included. Estimated pooled favorable outcome
      rate was 0.3746 (95% confidence interval [CI], 0.3165-0.4327), mortality was
      0.2950 (95% CI, 0.2390-0.3510). Pooled estimates showed that successful
      reperfusion (modified thrombolysis in cerebral ischemia scale 2b or 3) gained by
      SRT alone was 0.7317 (95% CI, 0.6532-0.8102) and final successful reperfusion
      rate with or without additional reperfusion procedures was 0.8834 (95% CI, 0.8279
      0.9390). Univariate analysis indicated that patients with successful reperfusion
      (OR, 2.05; P = 0.05), distal segment occlusion (OR, 2.03; P = 0.03), and
      cardioembolus origin (OR, 2.13; P = 0.01) were more likely to have favorable
      outcome (modified Rankin Scale score <=2 at 3 months). Study series that applied
      intra-arterial thrombolysis, angioplasty, or stenting as rescuing therapy had
      higher successful reperfusion rate but they did not show a higher rate of
      favorable outcome. CONCLUSIONS: SRT with or without additional treatment appeared
      to be effective for the treatment of BAO. Successful reperfusion, distal segment
      occlusion, and cardiac embolism were associated with favorable outcome. The
      overall benefit of lesions requiring additional reperfusion therapy was unclear.

PMID- 28427985
TI  - Ureter Injury as a Complication of Oblique Lumbar Interbody Fusion.
AB  - BACKGROUND: Oblique lumbar interbody fusion is a commonly used surgical method of
      achieving lumbar interbody fusion. There have been some reports about
      complications of oblique lumbar interbody fusion at the L2-L3 level. However, to
      our knowledge, there have been no reports about ureter injury during oblique
      lumbar interbody fusion. We report a case of ureter injury during oblique lumbar
      interbody fusion to share our experience. CASE DESCRIPTION: A 78-year-old male
      patient presented with a history of lower back pain and neurogenic intermittent
      claudication. He was diagnosed with spinal stenosis at L2-L3, L4-L5 level and
      spondylolisthesis at L4-L5 level. Symptoms were not improved after several months
      of medical treatments. Then, oblique lumbar interbody fusion was performed at L2
      L3, L4-L5 level. During the surgery, anesthesiologist noticed hematuria. A
      retrourethrogram was performed immediately by urologist, and ureter injury was
      found. Ureteroureterostomy and double-J catheter insertion were performed. The
      patient was discharged 2 weeks after surgery without urologic or neurologic
      complications. At 2 months after surgery, an intravenous pyelogram was performed,
      which showed an intact ureter. CONCLUSIONS: Our study shows that a low threshold
      of suspicion of ureter injury and careful manipulation of retroperitoneal fat can
      be helpful to prevent ureter injury during oblique lumbar interbody fusion at the
      upper level.

PMID- 28427986
TI  - Prognostic Implications of Extent of Resection in Glioblastoma: Analysis from a
      Large Database.
AB  - OBJECTIVE: To analyze the predictors for and clinical impact of gross total
      resection (GTR) in patients with glioblastoma (GBM). METHODS AND MATERIALS: The
      National Cancer Database was queried for patients with GBM diagnosed from 2004 to
      2013 with known survival and extent of resection. Patients were grouped based on
      extent of resection into biopsy alone, subtotal resection (STR), and GTR.
      Univariable analyses and multivariable analyses (MVAs) were performed to
      investigate factors associated with the likelihood of GTR and overall survival
      (OS) after diagnosis. RESULTS: A total of 27,865 patients met inclusion criteria.
      Factors associated with increased odds of GTR on MVA included later year of
      diagnosis, younger age, higher performance status, nonright-sided tumors,
      multifocal tumors, and O6-methylguanine-methyltransferase gene promoter non
      hypermethylated tumors (each P < 0.020). Factors associated with improved OS on
      MVA included younger patient age, female sex, race, lower comorbidity score,
      higher performance score, smaller tumor size, unifocality, O6-methylguanine
      methyltransferase hypermethylation, radiotherapy, chemotherapy, and facility
      volume (each P < 0.005). After we adjusted for each of these factors, compared
      with biopsy alone, GTR was associated with improved OS (hazard ratio 0.768, P <
      0.001), whereas STR (grouped together) was not (hazard ratio 0.995, P = 0.930).
      CONCLUSIONS: Although a prospective randomized trial on this topic is unlikely to
      be completed, this large retrospective analysis provides evidence to support the
      recommendation of GTR in patients with GBM. This study does not support a
      survival benefit of STR over biopsy alone (when grouped into these 2 groups),
      although there may be a subset of patients with near total resection who would
      benefit.

PMID- 28427987
TI  - Trajectory Planning and Guided Punctures with Isocentric Navigation in
      Posterolateral Endoscopic Lumbar Discectomy.
AB  - BACKGROUND: Posterolateral endoscopic trasforaminal discectomy (PELD) requires an
      ideal percutaneous puncture to place the working channel for endoscopic
      discectomy. The conventional blinded puncture relies on the surgeon's experience
      and repeated fluoroscopy, which may increase radiation exposure. This study aimed
      to introduce isocentric navigation to plan trajectory and guide punctures in
      PELD. METHODS: Technical note and clinical outcomes of patients undergoing PELD
      with isocentric navigation were recorded in this report. RESULTS: Four patients
      (3 female, 1 male) were included in this study. Age ranged from 21 to 67 years,
      and the body mass index ranged from 18.71 to 23.15 kg/m2. All of the included
      patients received just one puncture, and the radiation exposure time ranged from
      15 to 40 seconds. The operation time ranged from 58 to 75 minutes, and no
      significant complications were observed. All patients reported significant pain
      relief and improved surgical outcomes, as assessed by the Oswestry Disability
      Index and Macnab criteria. CONCLUSIONS: Isocentric navigation is feasible in
      planning the trajectory and guiding the punctures in PELD and could be considered
      as a potential practical tool to facilitate surgery.

PMID- 28427988
TI  - Obesity, Bariatric Surgery, and Vitamin D.
AB  - The high prevalence of obesity is a worldwide problem associated with multiple
      comorbidities, including cardiovascular diseases. Vitamin D deficiency with
      secondary hyperparathyroidism is common in obese individuals and can be
      aggravated after bariatric surgery. Moreover, there is no consensus on the
      optimal supplementation dose of vitamin D in postbariatric surgical patients. We
      present new data on the variability of 25(OH)D response to supplementation in
      postmenopausal obese women. It is important to recognize and treat vitamin D
      deficiency before bariatric surgery to avoid postoperative complications, such as
      metabolic bone disease with associated high fracture risk. The objective of this
      article is to discuss the bone metabolism consequences of vitamin D deficiency
      after bariatric surgery.

PMID- 28427990
TI  - Neuropeptide Y not involved in cutaneous vascular control in young human females
      taking oral contraceptive hormones.
AB  - We previously reported that the cutaneous vasodilator response to local warming
      in males required noradrenaline (NA) and neuropeptide-Y (NPY). Animal work has
      shown no role for NPY in female vascular control. We investigated the
      contribution of NA and NPY in human female cutaneous vascular control. Nine
      female and nine male participants volunteered. To elucidate whether synthetic
      oestrogen and progesterone altered cutaneous vascular responses, females were
      tested in high-hormone (HH) and low-hormone (LH) phases of oral contraceptive
      pill (OCP). Skin blood flow was assessed by laser-Doppler flowmetry and expressed
      as cutaneous vascular conductance (CVC). Treatments were: control, combined
      yohimbine and propranolol (YP), BIBP-3226, and bretylium tosylate (BT). YP and BT
      increased basal CVC (p<0.05) relative to control sites in both HH and LH phases;
      though, BIBP-3226 had no effect in either phase (both p>0.05). Males basal CVC
      was increased at all treated sites compared to control sites (all p<0.05). YP and
      BT treated sites were higher in HH compared to LH (p<0.05). YP and BT treatment
      reduced the local warming-induced vasodilatation compared to control sites
      (p>0.05) in both HH and LH phases; whereas, BIBP-3226 treatment had no effect
      (p>0.05). In males, the vasodilatation achieved at all treated sites was reduced
      compared to the untreated control site (p<0.05). Data indicate that NA, not NPY,
      regulates basal skin blood flow and contributes to the vasodilator response to
      local warming in young females; however, both NA and NPY play a role in both
      basal and heat-induced cutaneous responses in males.

PMID- 28427989
TI  - Egocentric and allocentric visuospatial working memory in premotor Huntington's
      disease: A double dissociation with caudate and hippocampal volumes.
AB  - Our brains represent spatial information in egocentric (self-based) or
      allocentric (landmark-based) coordinates. Rodent studies have demonstrated a
      critical role for the caudate in egocentric navigation and the hippocampus in
      allocentric navigation. We administered tests of egocentric and allocentric
      working memory to individuals with premotor Huntington's disease (pmHD), which is
      associated with early caudate nucleus atrophy, and controls. Each test had 80
      trials during which subjects were asked to remember 2 locations over 1-sec
      delays. The only difference between these otherwise identical tests was that
      locations could only be coded in self-based or landmark-based coordinates. We
      applied a multiatlas-based segmentation algorithm and computed point-wise
      Jacobian determinants to measure regional variations in caudate and hippocampal
      volumes from 3T MRI. As predicted, the pmHD patients were significantly more
      impaired on egocentric working memory. Only egocentric accuracy correlated with
      caudate volumes, specifically the dorsolateral caudate head, right more than
      left, a region that receives dense efferents from dorsolateral prefrontal cortex.
      In contrast, only allocentric accuracy correlated with hippocampal volumes,
      specifically intermediate and posterior regions that connect strongly with
      parahippocampal and posterior parietal cortices. These results indicate that the
      distinction between egocentric and allocentric navigation applies to working
      memory. The dorsolateral caudate is important for egocentric working memory,
      which can explain the disproportionate impairment in pmHD. Allocentric working
      memory, in contrast, relies on the hippocampus and is relatively spared in pmHD.

PMID- 28427991
TI  - Impact of the pneumococcal conjugate vaccine on serotype distribution of adult
      non-invasive Streptococcus pneumoniae isolates in Tokai region, Japan, 2008-2016.
AB  - The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in
      February 2010 markedly reduced the burden of invasive pneumococcal disease and
      changed serotype distribution in Japan. In November 2013, PCV7 was replaced by
      the 13-valent pneumococcal conjugate vaccine (PCV13). We investigated the
      serotype distribution and susceptibility trends of non-invasive Streptococcus
      pneumoniae isolates collected from adult patients. A total of 504 pneumococcal
      isolates were collected during 4 periods between 2008 and 2016 (Period 1; between
      June 2008 and April 2009, Period 2; between September 2010 and March 2011, Period
      3; between October 2011 and March 2012, Period 4; between August 2015 and January
      2016). The coverage of PCV7 and PCV13 significantly decreased from 38.6% and
      60.5% in Period 1 to 6.6% and 31.1% in Period 4. This change was mainly due to a
      large decrease in the frequency of serotype 19F, 6B, and 14. Serotype 3 was the
      most frequently isolated, and gradually increased. Additionally, non-PCV13
      serotypes 11A, 33F, and 35B significantly increased. Most of the PCV7 serotypes
      19F, 23F, 6B, and 14 had mutations of penicillin-binding protein genes and
      macrolide resistance genes, and these serotypes showed low susceptibilities to
      cefdinir and clarithromycin. On the other hand, a significant change in
      susceptibility to various antimicrobial agents was not observed throughout the
      study period, except for decreased susceptibility to carbapenems. Continuous
      surveillance studies of pneumococcal serotype changes and drug susceptibility are
      necessary in future.

PMID- 28427992
TI  - Invasive Haemophilus influenzae infections in children in Kamikawa subprefecture,
      Hokkaido, Japan, 2006-2015: The effectiveness of H. influenzae type b vaccine.
AB  - We evaluated 24 children with invasive Haemophilus influenzae infections between
      2006 and 2015 in Kamikawa subprefecture of Hokkaido, Japan. The most frequent
      disease was pneumonia in 12 cases (50.0%), followed by meningitis in 7 (29.2%)
      and bacteremia in 5 (20.8%). Patients ranged in age from 3 months to 12 years of
      age. Seventeen (70.8%) of the total were less than 2 years old. The incidence
      rate of H. influenzae infection varied from 15.1 to 36.3 per 100,000 population
      in the Kamikawa area during the period from 2006 through 2011. The corresponding
      rate decreased to 10.4 per 100,000 population in 2012, and there were no cases
      after 2013. Meningitis occurred in 1-2 patients annually from 2006 to 2011,
      showing an incidence rate of 4-10 per 100,000 population per year, while no cases
      were reported during or after 2012. No patients with invasive H. influenzae
      infection died, but sequelae were seen at discharge in 1 patient with meningitis,
      that had hydrocephalus and developmental delay. In Japan, introduction of the H.
      influenzae type b (Hib) vaccine was in November 2008. Initially, this vaccination
      was voluntary, resulting in a low vaccination rate. According to the national
      policy, and the self-pay burden for vaccination was decreased in December 2010,
      and the vaccination rate increased markedly to over 90%. This report provides a
      meaningful demonstration that introduction of the Hib vaccine markedly reduced
      invasive H. influenzae infections, exerting a beneficial effect in Japan, as it
      has in the world.

PMID- 28427993
TI  - Washout and non-washout solutions of a system describing microbial fermentation
      process under the influence of growth inhibitions and maximal concentration of
      yeast cells.
AB  - An unstructured model for the growth of yeast cell on glucose due to growth
      inhibitions by substrate, products, and cell density is discussed. The proposed
      model describes the dynamical behavior of fermentation system that shows multiple
      steady states for a certain regime of operating parameters such as inlet glucose
      and dilution rate. Two types of steady state solutions are found, namely washout
      and non-washout solutions. Furthermore, different numerical impositions to the
      two parameters put in evidence three results regarding non-washout solution: a
      unique locally stable non-washout solution, a unique locally stable non-washout
      solution towards which other nearby solutions exhibit damped oscillations, and
      multiple non-washout solutions where one is locally stable while the other is
      unstable. It is also found an optimal inlet glucose which produces the highest
      cell and ethanol concentration.

PMID- 28427994
TI  - Global dynamics in a stoichiometric food chain model with two limiting nutrients.
AB  - Ecological stoichiometry studies the balance of energy and multiple chemical
      elements in ecological interactions to establish how the nutrient content affect
      food-web dynamics and nutrient cycling in ecosystems. In this study, we formulate
      a food chain with two limiting nutrients in the form of a stoichiometric
      population model. A comprehensive global analysis of the rich dynamics of the
      targeted model is explored both analytically and numerically. Chaotic dynamic is
      observed in this simple stoichiometric food chain model and is compared with
      traditional model without stoichiometry. The detailed comparison reveals that
      stoichiometry can reduce the parameter space for chaotic dynamics. Our findings
      also show that decreasing producer production efficiency may have only a small
      effect on the consumer growth but a more profound impact on the top predator
      growth.

PMID- 28427996
TI  - No evidence that environmental enrichment during rearing protects against cocaine
      behavioral effects but as an intervention reduces an already established cocaine
      conditioned place preference.
AB  - OBJECTIVES: Environmental enrichment (EE) produces differential effects on
      psychostimulant-related behaviors. Therefore, we investigated whether the timing
      of EE exposure - during rearing and before cocaine exposure versus in adulthood
      and after cocaine exposure might be a determining factor. METHODS: In Experiment
      1, rats reared with EE or not (non-EE) were conditioned with cocaine (5, 10 or
      20mg/kg) in one compartment of a CPP apparatus and saline in the other, and later
      tested for cocaine CPP. In Experiment 2, locomotor activity in response to
      repeated injections of saline or cocaine was measured in rats raised with EE or
      non-EE. In Experiment 3 we measured the effects of EE or non-EE during rearing on
      food-based conditioned approach learning. In Experiment 4, rats were exposed to
      cocaine CPP conditioning then underwent 60days of EE or non-EE treatment after
      which they were tested for cocaine CPP. RESULTS: Our results show that rearing in
      EE did not reduce cocaine CPP or cocaine-induced locomotor activity (Experiments
      1 and 2) but significantly facilitated conditioned approach learning (Experiment
      3). On the other hand, EE treatment introduced after cocaine conditioning
      significantly reduced the expression of cocaine CPP (Experiment 4). CONCLUSIONS:
      These findings suggest that EE does not protect against cocaine's rewarding and
      stimulant effects but can reduce already established cocaine effects, suggesting
      that EE might be an effective treatment for cocaine addiction-related behaviors.

PMID- 28427995
TI  - Conditioned taste avoidance, conditioned place preference and hyperthermia
      induced by the second generation 'bath salt' alpha-pyrrolidinopentiophenone
      (alpha-PVP).
AB  - BACKGROUND: alpha-Pyrrolidinopentiophenone (alpha-PVP) has been reported to be
      rewarding in a variety of pre-clinical models. Given that a number of drugs of
      abuse have both rewarding and aversive effects, the balance of which influences
      addiction potential, the present study examined the aversive properties of alpha
      PVP by assessing its ability to induce taste avoidance. This assessment was made
      in a combined taste avoidance/place conditioning design that also allowed an
      evaluation of the relationship between alpha-PVP's aversive and rewarding
      effects. METHODS: Male Sprague-Dawley rats were exposed to a novel saccharin
      solution, injected with one of four doses of alpha-PVP (0, 0.3, 1.0 and 3.0mg/kg)
      (IP) and placed on one side of a place conditioning apparatus. The next day, they
      were injected with vehicle, given access to water and placed on the other side.
      Following four conditioning cycles, saccharin avoidance and place preferences
      were then assessed. The effects of alpha-PVP on body temperature were also
      examined. RESULTS: alpha-PVP induced dose-dependent taste avoidance as well as
      significant increases in time spent on the drug-paired side (although this effect
      was not dependent on dose). alpha-PVP also induced dose- and time-dependent
      hyperthermia. CONCLUSIONS: alpha-PVP induced significant taste avoidance whose
      strength relative to the psychostimulants methylenedioxypyrovalerone (MDPV) and
      cocaine paralleled their relative binding to the dopamine transporter. Similar to
      other drugs of abuse, alpha-PVP has both aversive and rewarding effects. It will
      be important to assess how various experiential and subject variables impact
      these effects and their balance to predict abuse liability.

PMID- 28427997
TI  - Distinct sequences and post-translational modifications in cardiac atrial and
      ventricular myosin light chains revealed by top-down mass spectrometry.
AB  - Myosin is the principal component of the thick filaments that, through
      interactions with the actin thin filaments, mediates force production during
      muscle contraction. Myosin is a hexamer, consisting of two heavy chains, each
      associated with an essential (ELC) and a regulatory (RLC) light chain, which bind
      the lever-arm of the heavy chain and play important modulatory roles in striated
      muscle contraction. Nevertheless, a comprehensive assessment of the sequences of
      the ELC and RLC isoforms, as well as their post-translational modifications, in
      the heart remains lacking. Herein, utilizing top-down high-resolution mass
      spectrometry (MS), we have comprehensively characterized the sequences and N
      terminal modifications of the atrial and ventricular isoforms of the myosin light
      chains from human and swine hearts, as well as the sites of phosphorylation in
      the swine proteins. In addition to the correction of disparities in the database
      sequences of the swine proteins, we show for the first time that, whereas the
      ventricular isoforms of the ELC and RLC are methylated at their N-termini, which
      is consistent with previous studies, the atrial isoforms of the ELC and RLC from
      both human and swine are Nalpha-methylated and Nalpha-acetylated, respectively.
      Furthermore, top-down MS with electron capture dissociation enabled localization
      of the sites of phosphorylation in swine RLC isoforms from the ventricles and
      atria to Ser14 and Ser22, respectively. Collectively, these results provide new
      insights into the sequences and modifications of myosin light chain isoforms in
      the human and swine hearts, which will pave the way for a better understanding of
      their functional roles in cardiac physiology and pathophysiology.

PMID- 28427999
TI  - SERPINB1 ameliorates acute lung injury in liver transplantation through ERK1/2
      mediated STAT3-dependent HO-1 induction.
AB  - BACKGROUND: Postoperative acute lung injury (ALI) is a severe complication after
      liver transplantation, which severely affects postoperative patients' survival.
      The underlying mechanism is largely unknown and effective treatment limited. We
      explored the role of serpin protease inhibitor B1 (SERPINB1), a potent inhibitor
      of neutrophil serine proteases, in ALI in liver transplantation and its interplay
      with signal transducer and activator of transcription 3 (STAT3) and heme
      oxygenase-1 (HO-1). METHODS: Sprague-Dawley rats underwent orthotopic autologous
      liver transplantation (OALT) were treated with recombinant SB1 (rSB1) in the
      absence or presence of STAT3 specific inhibitor, WP1066. Then SB1-siRNA was used
      to knockdown endogenous SERPINB1. Also, alveolar epithelial cells RLE-6TN and
      BEAS-2B were exposed to TNF-alpha without or with SERPINB1 and the roles of STAT3
      and HO-1 were examined by respective gene knockdown. Finally, rats were treated
      with ERK1/2 inhibitor U0126, p38 MAPK inhibitor SB20358, or JNK inhibitor
      SP600125 after rSB1 pretreatment and then subjected to OALT. RESULTS: OALT
      resulted in increased pulmonary inflammation and oxidative stress, accompanied by
      severe lung injury that was coincident with increased pulmonary SERPINB1, HO-1,
      and STAT3. SERPINB1 gene knockdown increased post-OALT lung injury and pulmonary
      inflammation. rSB1 administration dose-dependently reduced post-OALT lung injury
      and decreased pulmonary inflammation and oxidative stress with concomitant
      enhanced HO-1 and STAT3 protein expression. These protective effects of SERPINB1
      were abolished by STAT3 inhibition. Similarly, in RLE-6TN cells and BEAS-2B
      cells, TNF-alpha induced cell injury and increased HO-1 and STAT3. SERPINB1
      further increased HO-1 and STAT3 protein expression and attenuated TNF-alpha
      induced cellular oxidative stress, apoptotic cells, and mitochondria damage,
      which were cancelled by STAT3 or HO-1 gene knockdown. Furthermore, these SERPINB1
      mediated STAT3/HO-1 activation and pulmonary protective effects were abolished by
      inhibition of ERK1/2 but not p38 MAPK or JNK. CONCLUSIONS: SERPINB1 decreased
      inflammation, ameliorated oxidative stress in the lung, and attenuated ALI in
      rats with OALT by activating HO-1 and it does so through STAT3 and it does so by
      activating ERK1/2.

PMID- 28427998
TI  - Nitric oxide-regulated proteolysis of human CYP2B6 via the ubiquitin-proteasome
      system.
AB  - We showed previously that rat cytochrome P450 CYP2B1 undergoes NO-dependent
      proteasomal degradation in response to inflammatory stimuli, and that the related
      human enzyme CYP2B6 is also down-regulated by NO in primary human hepatocytes. To
      investigate the mechanism of CYP2B6 down-regulation, we made several cell lines
      (HeLa and HuH7 cells) in which native CYP2B6 or CYP2B6 with a C-terminal V5 tag
      (CYP2B6V5) are expressed from a lentiviral vector with a cytomegalovirus
      promoter. Native CYP2B6 protein was rapidly down-regulated in HeLa cells within
      3h of treatment with the NO donor (Z)-1-[2-(2-Aminoethyl)-N-(2
      ammonioethyl)amino]diazen-1-ium-1,2-diolate, while its mRNA level was not down
      regulated. Treatment of the cells with the NO donor (Z)-1-[N-(3-aminopropyl)-N-(3
      ammoniopropyl)amino]diazen-1-ium-1,2-diolate also resulted in rapid down
      regulation of CYP2B6 activity, measured as the formation of 7-hydroxy-4
      trifluoromethylcoumarin, as well as 2B6 protein in the CYP2B6 HeLa cell line.
      CYP2B6V5 was also down-regulated by NO donors in HuH7 cells. Down-regulation was
      observed in the presence of cycloheximide, demonstrating that this occurs via a
      post-translational mechanism. We generated a HeLa cell line expressing both
      CYP2B6V5 and human nitric oxide synthase 2 (NOS2), the latter under positive
      control by tetracycline. The cellular NO produced by doxycycline treatment also
      effectively down-regulated CYP2B6 protein, which was blocked by the co-treatment
      with the NOS2 competitive inhibitor L-NG-nitroarginine methyl ester (L-NAME). We
      next investigated the proteolytic enzymes responsible for NO-dependent CYP2B6
      degradation. Neither calpain inhibitors (N-Acetyl-L-leucyl-L-leucyl-L
      norleucinal, carbobenzoxy-valinyl-phenylalaninal), nor lysosomal protease
      inhibitors (3-methyladenine and chloroquine) inhibited the NO dependent CYP2B6V5
      down-regulation. The proteasome inhibitors MG132 and bortezomib attenuated, but
      did not completely block the NO-induced down-regulation in the HuH7 cell line.
      However, when cells were co-treated with NO donor and proteasome inhibitors, high
      molecular mass species could be detected on native CYP2B6 as well as CYP2B6V5
      Western blots. Further investigation demonstrated that CYP2B6 protein was
      polyubiquitinated and this was dramatically enhanced by co-treatment with NO
      donor and bortezomib. Taken together, our data demonstrate that CYP2B6 is down
      regulated in an NO-dependent manner via ubiquitination and proteasomal
      degradation.

PMID- 28428000
TI  - Selected oxidative stress biomarkers in antenatal diagnosis as 11-14 gestational
      weeks.
AB  - The primary objective in modern obstetrics and prenatal diagnosis is to predict
      risks of congenital abnormalities. The aim of the research was to assess the
      correlation between selected oxidative stress biomarkers with the risk of foetal
      chromosomal aberration evaluated at the first trimester screening. A series of
      studies show that balanced free radical activity and oxidative homeostasis are
      essential for proper bodily growth and function. Reactive oxygen species (ROS)
      may be one of the factors associated with disruption of cell cycle and tissue
      development, thus leading to developmental abnormalities. That's why it's so
      important to examine connection between level of oxidative stress and congenital
      abnormalities. Using ultrasonography examinations between 11-13+6d gestational
      weeks combined with serum levels of pregnancy associated plasma protein A and
      human chorionic gonadotropin and spectrophotometric analysis of oxidative stress
      markers such as glutathione (GSH), S-transferase, S-nitrosothiols (RSNO), trolox
      equivalent antioxidant capacity (TEAC), protein and nitrites we tried to find
      correlation between birth defects and oxidative stress status. In conclusion, our
      analysis suggests that elevated maternal serum levels of protein, S-transferase
      and TEAC as well as decreased maternal serum levels of GSH and protein correlated
      with the risk of chromosomal aberrations and congenital developmental defects in
      a foetus.

PMID- 28428001
TI  - Cholesterol and related sterols autoxidation.
AB  - Cholesterol is a unique lipid molecule providing the building block for
      membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol
      involves several enzymes acting on the sterol nucleus or the isooctyl tail. In
      the recent years, research interest has been focused on oxysterols, cholesterol
      derivatives generated by the addition of oxygen to the cholesterol backbone.
      Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of
      cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is
      initiated by free radical species, such as those arising from the
      superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs
      stoichiometrically by non-radical highly reactive oxygen species such as singlet
      oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive
      species has raised considerable interest for mechanistic studies and for the
      potential biological activity of oxysterols, as well as for the use of oxysterols
      as biomarkers for the non-invasive study of oxidative stress in vivo.

PMID- 28428002
TI  - Performance during competition and competition outcome in relation to
      testosterone and cortisol among women.
AB  - A contribution to a special issue on Hormones and Human Competition. This study
      investigated the relation between competition, testosterone (T), and cortisol (C)
      in women. One hundred and twenty female participants competed against a male
      confederate in a computerized laboratory task. The task was preprogrammed so that
      half the women won and half of the women lost the competition. T and C
      concentrations were measured in saliva samples collected at four time points
      before and after the competition. Accuracy and reaction time during the
      competition were recorded. T and C increased directly after the competition,
      though not significantly for C, and then decreased over time regardless of the
      competition outcome. Regression analyses demonstrated that baseline T was
      significantly and positively associated with competition accuracy, though only in
      individuals who were low in C. Individuals who were high in C showed no relation
      between T and accuracy. This relation was further qualified by competition
      outcome. Losers of the competition showed a significant positive relation between
      baseline T levels and competition accuracy, though only if they were low in C. No
      relation was found between T and accuracy in losers who were high in C. Winners
      of the competition showed no relation between T and accuracy, regardless of
      whether C levels were high or low. These results are in line with the dual
      hormone hypothesis, whereby the effects of T on status-seeking behaviors are
      dependent on C levels for individuals whose status is threatened.

PMID- 28428003
TI  - Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the
      Erk1/2 MAPK and STAT3 pathways.
AB  - Cigarette smoke (CS) is a major risk factor for the development of chronic
      obstructive pulmonary disease (COPD). Our previous studies have indicated that
      Rac1 is involved in lipopolysaccharide-induced pulmonary injury and CS-mediated
      epithelial-mesenchymal transition. However, the contribution of Rac1 activity to
      CS-induced lung inflammation remains not fully clear. In this study, we
      investigated the regulation of Rac1 in CS-induced pulmonary inflammation. Mice or
      16HBE cells were exposed to CS or cigarette smoke extract (CSE) to induce acute
      inflammation. The lungs of mice exposed to CS showed an increase in the release
      of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC), as well as an
      accumulation of inflammatory cells, indicating high Rac1 activity. The exposure
      of 16HBE cells to CSE resulted in elevated Rac1 levels, as well as increased
      release of IL-6 and interleukin-8 (IL-8). Selective inhibition of Rac1
      ameliorated the release of IL-6 and KC as well as inflammation in the lungs of CS
      exposed mice. Histological assessment showed that treatment with a Rac1
      inhibitor, NSC23766, led to a decrease in CD68 and CD11b positive cells and the
      infiltration of neutrophils and macrophages into the alveolar spaces. Selective
      inhibition or knockdown of Rac1 decreased IL-6 and IL-8 release in 16HBE cells
      induced by CSE, which correlated with CSE-induced Rac1-regulated Erk1/2 mitogen
      activated protein kinase (MAPK) and signal transducer and activator of
      transcription-3 (STAT3) signaling. Our data suggest an important role for Rac1 in
      the pathological alterations associated with CS-mediated inflammation. Rac1 may
      be a promising therapeutic target for the treatment of CS-induced pulmonary
      inflammation.

PMID- 28428004
TI  - Long noncoding RNA AWPPH promotes hepatocellular carcinoma progression through
      YBX1 and serves as a prognostic biomarker.
AB  - Long noncoding RNAs (lncRNAs) have been shown to play important roles in various
      cancers. However, the clinical significances and biological roles of lncRNAs in
      hepatocellular carcinoma (HCC) remain largely unknown. In this study, using
      online-available data sets and quantitative real-time PCR, we identified a novel
      lncRNA termed lncRNA-AWPPH, which is highly expressed in HCC tissues. Its
      upregulation is correlated with encapsulation incomplete, microvascular invasion,
      advanced TNM stage and BCLC stage. Cox proportional hazards regression analysis
      revealed that high lncRNA-AWPPH expression is an independent prognostic factor
      for poor recurrence-free and overall survival. Functional experiments showed that
      overexpression of lncRNA-AWPPH promotes HCC cell proliferation and migration in
      vitro, and tumor growth and metastasis in vivo. Conversely, depletion of lncRNA
      AWPPH has opposite effects on HCC. Mechanistically, lncRNA-AWPPH interacts with
      YBX1, promotes YBX1-mediated activation of SNAIL1 translation, and upregulates
      SNAIL1 expression. Furthermore, lncRNA-AWPPH promotes YBX1-mediated activation of
      PIK3CA transcription, upregulates PIK3CA expression, and activates PI3K/AKT
      pathway. Depletion of YBX1 abolishes the effects of lncRNA-AWPPH on SNAIL1 and
      PIK3CA, and also the biological roles of lncRNA-AWPPH on HCC cells. In
      conclusion, this study identifies a novel lncRNA termed lncRNA-AWPPH which is
      highly expressed in HCC, indicates poor prognosis of HCC patients, and promotes
      HCC cell proliferation, migration, and in vivo tumor growth and metastasis via a
      novel regulatory mechanism of interacting with YBX1.

PMID- 28428005
TI  - Older age impacts on survival outcome in patients receiving curative surgery for
      solid cancer.
AB  - BACKGROUND: Given the global increase in aging populations and cancer incidence,
      understanding the influence of age on postoperative outcome after cancer surgery
      is imperative. This study aimed to evaluate the impact of age on survival outcome
      in solid cancer patients receiving curative surgery. METHODS: A total of 37,288
      patients receiving curative surgeries for solid cancers between 2007 and 2012 at
      four affiliated Chang Gung Memorial Hospital were included in the study. All
      patients were categorized into age groups by decades for survival analysis.
      RESULTS: The percentages of patient populations aged <40 years, 40-49 years, 50
      59 years, 60-69 years, 70-79 years, and >=80 years were 9.7%, 17.7%, 27.8%,
      22.1%, 16.9%, and 5.7%, respectively. The median follow-up period was 38.9 months
      (range, 22.8-60.4 months) and the overall, cancer-specific, and noncancer
      specific mortality rates were 26.0%, 17.6%, and 8.5%, respectively. The overall
      mortality rate of patients in different age groups were 18.5%, 21.1%, 22.0%,
      25.3%, 35.3%, and 49.0%, respectively. Compared to patients aged <40 years, more
      significant decrease in long-term survival were observed in aging patients.
      Multivariate analysis showed higher postoperative short-term mortality rates in
      patients older than 70 years, and the adjusted odds ratio of mortality risk
      ranged from 1.47 to 1.74 and 2.26 to 3.03 in patients aged 70-79 years and >=80
      years, respectively, compared to those aged <40 years. CONCLUSION: Aging was a
      negative prognostic factor of survival outcome in solid cancer patients receiving
      curative surgery. After adjustment of other clinicopathologic factors, the
      influence of age on survival outcome was less apparent in the elderly.

PMID- 28428006
TI  - The relation between the location and the perforation rate of lung hydatid cysts
      in children.
AB  - BACKGROUND/OBJECTIVE: The pressure, size, and central or peripheral location of
      lung hydatid cysts are the most studied topics among the factors affecting
      perforation. The aim of this study is to investigate the relation between the
      location and the perforation rate of lung hydatid cysts in children. METHODS: 197
      patients under the age of 16 years, who were operated between January 2000 and
      December 2016 due to pulmonary hydatid cysts, were evaluated retrospectively.
      Patients who had giant hydatid cysts (n = 27), bilateral hydatid cysts (n = 24),
      and more than one cyst in one lung (n = 12) were excluded to create a more
      homogeneous group to enable investigation of the relation between the location
      and the perforation rates of hydatid cysts. Finally, 134 patients who had only
      one hydatid cyst were classified into two groups: Group 1 with perforated cysts
      and Group 2 with intact hydatid cysts. RESULTS: 70.9% of the patients were male.
      In total, 134 cysts were detected and 41% were perforated. The highest
      perforation rates were detected in the right middle lobe (70%) and the lingula
      (66.7%). There was a statistically significant difference between the location of
      the cysts and the perforation rates (p = 0.018). Also hydatid cysts located in
      the right middle lobe and the lingula had higher postoperative complication rates
      than hydatid cysts located in the upper and lower lobes (p = 0.018). CONCLUSION:
      We recommend surgical treatment as soon as possible in children with hydatid
      cysts located in the right middle lobe and lingula to prevent the risk of
      perforation.

PMID- 28428007
TI  - Identification and characterization of two RNA silencing suppressors encoded by
      ophioviruses.
AB  - Citrus psorosis virus and Mirafiori lettuce big-vein virus are two members of the
      genus Ophiovirus, family Ophioviridae. So far, how these viruses can interfere in
      the antiviral RNA silencing pathway is not known. In this study, using a local
      GFP silencing assay on Nicotiana benthamiana, the 24K-25K and the movement
      protein (MP) of both viruses were identified as RNA silencing suppressor
      proteins. Upon their co-expression with GFP in N. benthamiana 16c plants, the
      proteins also showed to suppress systemic RNA (GFP) silencing. The MPCPsV and
      24KCPsV proteins bind long (114 nucleotides) but not short-interfering (21 nt)
      dsRNA, and upon transgenic expression, plants showed developmental abnormalities
      that coincided with an altered miRNA accumulation pattern. Furthermore, both
      proteins were able to suppress miRNA-induced silencing of a GFP-sensor construct
      and the co-expression of MPCPsV and 24KCPsV exhibited a stronger effect,
      suggesting they act at different stages of the RNAi pathway.

PMID- 28428008
TI  - Force development and intracellular Ca2+ in intact cardiac muscles from gravin
      mutant mice.
AB  - Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A
      (PKA), beta2-adrenergic receptor (beta2-AR), protein phosphatase 2B and protein
      kinase C. Gravin facilitates beta2-AR-dependent signal transduction through PKA
      to modulate cardiac excitation-contraction coupling and its removal positively
      affects cardiac contraction. Trabeculae from the right ventricles of gravin
      mutant (gravin-t/t) mice were employed for force determination. Simultaneously,
      corresponding intracellular Ca2+ transient ([Ca2+]i) were measured. Twitch force
      (Tf)-interval relationship, [Ca2+]i-interval relationship, and the rate of decay
      of post-extrasysolic potentiation (Rf) were also obtained. Western blot analysis
      were performed to correlate sarcomeric protein expression with alterations in
      calcium cycling between the WT and gravin-t/t hearts. Gravin-t/t muscles had
      similar developed force compared to WT muscles despite having lower [Ca2+]i at
      any given external Ca2+ concentration ([Ca2+]o). The time to peak force and peak
      [Ca2+]i were slower and the time to 75% relaxation was significantly prolonged in
      gravin-t/t muscles. Both Tf-interval and [Ca2+]i-interval relations were
      depressed in gravin-t/t muscles. Rf, however, did not change. Furthermore,
      Western blot analysis revealed decreased ryanodine receptor (RyR2)
      phosphorylation in gravin-t/t hearts. Gravin-t/t cardiac muscle exhibits
      increased force development in responsiveness to Ca2+. The Ca2+ cycling across
      the SR appears to be unaltered in gravin-t/t muscle. Our study suggests that
      gravin is an important component of cardiac contraction regulation via increasing
      myofilament sensitivity to calcium. Further elucidation of the mechanism can
      provide insights to role of gravin if any in the pathophysiology of impaired
      contractility.

PMID- 28428009
TI  - Effect of methylparaben in Artemia franciscana.
AB  - In this study, the toxicity of methylparaben (MeP) an emerging contaminant, was
      analysed in the sexual species Artemia franciscana, due to its presence in
      coastal areas and marine saltworks in the Mediterranean region. The acute
      toxicity (24h-LC50) of MeP in nauplii was tested and its chronic effect (9days)
      evaluated by measuring survival and growth under two sublethal concentrations
      (0.0085 and 0.017mg/L). Also, the effect on several key enzymes involved in:
      antioxidant defences (catalase (CAT) and gluthathion-S-transferase (GST)), neural
      activity (cholinesterase (ChE)) and xenobiotic biotransformation
      (carboxylesterase (CbE), was assessed after 48h under sublethal exposure. The
      results of acute exposure indicate that MeP is harmful to A. franciscana (24h
      LC50=36.7mg/L). MeP causes a decrease in CAT activity after 48h exposure to both
      concentration tested, that points out at the oxidative stress effect of MeP in A.
      franciscana. However, no significant effect on ChE, CbE and GST activities was
      found. In addition, MeP does not affect survival and growth in chronic exposure
      at the sublethal concentrations tested. The results of this study indicate that
      MeP is not a threat for A. franciscana under the experimental conditions used.
      Additional studies should be done considering long-term exposure and reproduction
      studies to analyse the potential risk of MeP as emerging contaminant in marine
      and hypersaline environments.

PMID- 28428010
TI  - A strategy of faster movements used by elderly humans to lift objects of
      increasing weight in ecological context.
AB  - It is not known whether, during the course of aging, changes occur in the motor
      strategies used by the CNS for lifting objects of different weights. Here, we
      analyzed the kinematics of object-lifting in two different healthy groups (young
      and elderly people) plus one well-known deafferented patient (GL). The task was
      to reach and lift onto a shelf an opaque cylindrical object with changing weight.
      The movements of the hand and object were recorded with electromagnetic sensors.
      In an ecological context (i.e. no instruction was given about movement speed), we
      found that younger participants, elderly people and GL did not all move at the
      same speed and that, surprisingly, elder people are faster. We also observed that
      the lifting trajectories were constant for both the elderly and the deafferented
      patient while younger participants raised their hand higher when the object
      weighed more. It appears that, depending on age and on available proprioceptive
      information, the CNS uses different strategies of lifting. We suggest that elder
      people tend to optimize their feedforward control in order to compensate for less
      functional afferent feedback, perhaps to optimize movement time and energy
      expenditure at the expense of high precision. In the case of complete loss of
      proprioceptive input, however, compensation follows a different strategy as
      suggested by GL's behavior who moved more slowly compared to both our younger and
      older participants.

PMID- 28428011
TI  - CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis.
AB  - BACKGROUND: The role of the macrophages in cystic fibrosis (CF) lung disease has
      been poorly studied. We hypothesized that alternatively activated M2 macrophages
      are abnormal in CF lung disease. METHODS: Blood samples were collected from
      adults (n=13) children (n=27) with CF on admission for acute pulmonary
      exacerbation and when clinically stable. Monocytes were differentiated into
      macrophages and polarized into classical (M1) and alternatively-activated (M2)
      phenotypes, function determined ex-vivo and compared with healthy controls.
      RESULTS: In the absence of functional cystic fibrosis trans-membrane conductance
      regulator (CFTR), either naturally in patients with CF or induced with CFTR
      inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to
      polarize into M2s associated with a post-transcriptional failure to produce and
      express IL-13Ralpha1 on the macrophage surface Polarization to the M1 phenotype
      was unaffected. CONCLUSIONS: CFTR-dependent imbalance of macrophage phenotypes
      and functions could contribute to the exaggerated inflammatory response seen in
      CF lung disease.

PMID- 28428012
TI  - [Retrospective study of children referred from paediatric intensive care to
      palliative care: Why and for what].
AB  - INTRODUCTION: The creation of paediatric palliative care units (PPCU) could
      optimise the management of children with palliative focus after admission to a
      paediatric intensive care unit (PICU). This study describes the clinical and
      epidemiological characteristics of children referred from PICU to the PPCU of the
      Autonomous Community of Madrid (CAM). The overall treatment, relapses, re
      admissions, and deaths, if occurred, are described. PATIENTS AND METHOD: A
      retrospective review was performed using the medical records from children
      transferred from the CAM paediatric intensive care units to the paediatric
      palliative care unit (1 March 2008-31 January 2015). RESULTS: A total of 41
      patients were included (26 male/15 female) with a median age of 33 months (range
      1-228). In the follow by the PPCU follow-up, the main approaches were respiratory
      (invasive ventilation with tracheostomy tube 8/41), nutritional (gastrostomy in
      20/41), and pharmacological (anti-epileptics in 29/41 and 34/41 on antibiotic
      treatment). Hospital re-admission was required by 11/41 patients, with no re
      admissions to PICU. Of the 13/41 patients who died, 9/13 was at home, with all of
      them accompanied by the primary caregivers and family, and only 1/9 with the
      presence of the home team. CONCLUSIONS: The palliative approach at home is
      feasible in children, and the integration of PPCU could optimise the
      comprehensive care of previously critically ill children. It is necessary to
      achieve an optimal domiciliary care should be achieved, and not just because of
      patient death. More observational, multicentre and prospective studies are needed
      to confirm these findings.

PMID- 28428013
TI  - [The monophasic pattern in oral glucose tolerance test as a predictive risk
      factor of type 2 diabetes in obese paediatric patients].
AB  - INTRODUCTION: The onset of obesity at young ages is strongly associated with the
      early development of type 2diabetes (T2D). The shape of the curves of glucose and
      insulin curves during an oral glucose tolerance test (OGTT) could predict the
      risk of developing T2D. OBJECTIVE: To analyse the morphology of the OGTT and
      determine T2D risk factors in a mainly Caucasian population of children and
      adolescents. METHODS: Observational retrospective study including 588 patients
      (309 males, 279 females) with a mean age of 11.1+/-2years, and of whom 90.3% were
      Caucasian. Risk factors for T2D were compared in patients with a monophasic or
      biphasic pattern during the performance of an OGTT, as well as anthropometric and
      biochemical variables, insulin resistance, and beta-cell function. RESULTS: The
      shape of the glucose curve was monophasic in 50.2% of patients (50.8% male),
      biphasic in 48.5% (47.6% males), and indeterminate in 1.3%. The monophasic
      pattern showed lower insulin-sensitivity and worse beta-cell function. Patients
      with a biphasic pattern had a higher BMI, waist circumference, and blood
      pressure, although the results were not significant. Latin-American patients had
      significantly lower serum glucose levels with higher insulin levels during the
      OGTT. CONCLUSIONS: The pattern of response to an OGTT reflects different
      metabolic phenotypes. Paediatric patients with a biphasic pattern have lower risk
      profiling for T2D. The performing of an OGTT could be useful to implement early
      intervention strategies in children and adolescents with obesity, in order to
      prevent the development of pre-diabetes or T2D.

PMID- 28428014
TI  - Concussion induces focal and widespread neuromorphological changes.
AB  - Concussion induces transient, and oftentimes chronic, lingering impairment to
      mental functioning, which must be driven by some underlying neurobiological
      perturbation - however, the physical changes related to sequelae are difficult to
      detect. Previous imaging studies on concussion have focused on alterations to
      cortical anatomy, but few have examined the cerebrum, subcortex, and cerebellum.
      Here, we present an analysis of these structures in a single cohort (all males,
      21 patients, 22 controls) using MRI and diagnosed with a single-concussive
      episode in the acute and sub-acute stages of injury. Structural images were
      segmented into 78 cortical brain regions and 81,924 vertices using the CIVET
      algorithm. Subcortical volumetric analyses of the cerebellum, thalamus, globus
      pallidus, caudate and putamen were conducted following segmentation. Participants
      with concussion were found to have reduced white and grey matter volume, total
      cortical volume, as well as cortical thinning, primarily in left frontal areas.
      No differences were observed in the cerebellum or subcortical structures. In
      conclusion, just a single concussive episode induces measurable changes in brain
      structure manifesting as diffuse and local patterns of altered neuromorphometry.

PMID- 28428015
TI  - Plasma neurofilament light chain levels in Alzheimer's disease.
AB  - Plasma neurofilament light (NFL) levels may be a marker of neuronal injury. We
      examined whether plasma NFL might be a potential biomarker for the prodromal and
      dementia stages of AD. Participants included 193 cognitively normal (CN), 198
      amnestic mild cognitive impairment (aMCI) and 187 Alzheimer's disease (AD)
      individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI).
      Plasma NFL levels were examined by the Single Molecule array (Simoa) technique.
      Our results showed significantly increased plasma NFL levels in both AD
      (50.9pg/ml) and aMCI (43.0pg/ml) groups compared to CN (34.7pg/ml) group (both
      p<0.001), but with substantial overlap between the groups. Plasma NFL levels in
      AD group was also markedly increased, compared with aMCI group (p<0.001). Plasma
      NFL levels were positively associated with age (r=0.355, p<0.001) and negatively
      with global cognition (r=-0.355, p<0.001) in all subjects. Our results suggest
      that plasma NFL levels may not be a useful biomarker for the diagnosis of
      prodromal and dementia stages of AD.

PMID- 28428016
TI  - The role of low level laser therapy on neuropathic pain relief and interleukin-6
      expression following spinal cord injury: An experimental study.
AB  - INTRODUCTION: The effect of Low Level Laser Therapy (LLLT) as a non-invasive
      treatment of spinal cord injury (SCI) is still under investigation. Therefore,
      the present study aimed to evaluate the effectiveness of LLLT on neuropathic pain
      and interleukin-6 (IL-6) expression following SCI in male rats. METHODS: 46 adult
      male rats were divided into 5 groups of control, SCI, treatment with
      methylprednisolone sodium succinate (MPSS), 1-week LLLT and 2-week LLLT. Animals
      underwent behavioral evaluations for motor behavior, level of allodynia and
      hyperalgesia every week. At the end, spinal cord was extracted and IL-6 level was
      assessed by ELISA method. RESULTS: Treatment with MPSS and 2-week LLLT had led to
      motor function recovery (df: 24, 145; F=223.5; p <0.001). SCI did not affect
      mechanical (df: 24, 145; F=0.5; p=0.09), and cold allodynia (df: 24, 145; F=0.3;
      p=0.17) but significantly increased mechanical (df: 24, 145; F=21.4; p<0.001) and
      heat hyperalgesia (df: 24, 145; F=16.1; p<0.001). Treatment with MPSS and 1 and 2
      weeks LLLT improved mechanical hyperalgesia (p<0.05) and heat hyperalgesia
      (p<0.01). The increased level of IL-6 following SCI was also compensated by
      administration of MPSS or LLLT (df: 4, 10; F=8.74; p=0.003). CONCLUSION: Findings
      show that long periods of LLLT have better effects in improving the complication
      of SCI. In summation, since LLLT does not cause the side effects of MPSS, long
      term use of LLLT may be a proper alternative for MPSS in decreasing post SCI side
      effects.

PMID- 28428017
TI  - Outcomes and toxicity following high-dose radiation therapy in 15 fractions for
      non-small cell lung cancer.
AB  - PURPOSE: Accelerated hypofractionated radiation therapy (AHRT) is increasingly
      used for select lung cancer patients. We evaluated clinical outcomes and
      predictors of pulmonary/esophageal toxicity in patients treated with >=52.5 Gy in
      15 fractions. METHODS AND MATERIALS: We evaluated 229 patients treated with
      radiation therapy doses >=52.5 Gy in 15 fractions for non-small cell lung cancer
      from January 2009 through January 2016. Toxicity was scored using Common
      Terminology Criteria for Adverse Events, v4.0. Univariate and multivariate
      logistic regression was used to identify predictors of toxicity. Overall
      survival, progression-free survival, and local control were estimated using the
      Kaplan-Meier method. Predictors of clinical outcome were modeled using Cox
      proportional hazards regression. RESULTS: Median follow-up was 7 months. Forty
      two patients (19%) developed grade >=2 pneumonitis, and 9 (4%) developed grade
      >=3 esophagitis. In multivariate analysis, age >75 years (odds ratio [OR], 2.56;
      95% confidence interval [CI], 1.24-5.25; P = .01) and percentage of lung volume
      receiving doses of >10 Gy higher than 32% were associated with grade >=2
      pneumonitis (OR, 2.79; 95% CI, 1.39-5.79; P = .005). On univariate analysis,
      esophagus mean dose >=17 Gy (OR, 10.14; 95% CI, 1.82-189.8; P = .006), gross
      tumor volume size >=71 cm3 (P = .002), and planning target volume size >=409 cm3
      (P = .02) were associated with development of grade >=3 esophagitis. In patients
      with stage II/III disease (n = 73), median local control was not reached, median
      overall survival was 14 months, and median progression-free survival was 6
      months. CONCLUSIONS: AHRT in 15 fractions can be safe and effective.
      Consideration for using AHRT with immunotherapy and sequential chemotherapy for
      improved out-of-radiation field and distant control is warranted.

PMID- 28428018
TI  - Visual analytics dashboard to explore the relationship of unscheduled treatment
      interruptions and variations in airway management for children undergoing
      external beam radiation therapy.

PMID- 28428019
TI  - Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of
      an ASTRO Evidence-Based Clinical Practice Guideline.
AB  - PURPOSE: To present evidence-based guidelines for the treatment of oropharyngeal
      squamous cell carcinoma (OPSCC) with definitive or adjuvant radiation therapy
      (RT). METHODS AND MATERIALS: The American Society for Radiation Oncology convened
      the OPSCC Guideline Panel to perform a systematic literature review investigating
      the following key questions: (1) When is it appropriate to add systemic therapy
      to definitive RT in the treatment of OPSCC? (2) When is it appropriate to deliver
      postoperative RT with and without systemic therapy following primary surgery for
      OPSCC? (3) When is it appropriate to use induction chemotherapy in the treatment
      of OPSCC? (4) What are the appropriate dose, fractionation, and volume regimens
      with and without systemic therapy in the treatment of OPSCC? RESULTS: Patients
      with stage IV and stage T3 N0-1 OPSCC treated with definitive RT should receive
      concurrent high-dose intermittent cisplatin. Patients receiving adjuvant RT
      following surgical resection for positive surgical margins or extracapsular
      extension should be treated with concurrent high-dose intermittent cisplatin, and
      individuals with these risk factors who are intolerant of cisplatin should not
      routinely receive adjuvant concurrent systemic therapy. Induction chemotherapy
      should not be routinely delivered to patients with OPSCC. For patients with stage
      IV and stage T3 N0-1 OPSCC ineligible for concurrent chemoradiation therapy,
      altered fractionation RT should be used. CONCLUSION: The successful management of
      OPSCC requires the collaboration of radiation, medical, and surgical oncologists.
      When high-level data are absent for clinical decision-making, treatment
      recommendations should incorporate patient values and preferences to arrive at
      the optimal therapeutic approach.

PMID- 28428020
TI  - Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.
AB  - In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS #
      87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26
      weeks. A 4-week recovery period was added to observe delayed or reversible
      toxicity. Measurements included body weight, food consumption, clinical
      observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry,
      hematology, organ weight, gross necropsy, and histopathological examination.
      Except for transient diarrhea or vomiting, no treatment-related adverse effects
      were noted. In the mid-dose groups, transitional diarrhea was observed in the
      initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were
      observed episodically over the duration of treatment. However, they disappeared
      after XOS was withdrawn in the recovery period. Although there was a tendency
      toward less weight gain in the high-dose group animal group, this is typical in
      animals and humans fed non-digestible carbohydrates. This chronic toxicity study
      demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500
      mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54
      for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g
      XOS in human adults weighing 60-80 kg.

PMID- 28428021
TI  - A pilot study of mechanical chest compression with the LifeLine ARM device during
      simulated cardiopulmonary resuscitation: Reply.

PMID- 28428022
TI  - Cloning and identification of a novel steroid 11alpha-hydroxylase gene from
      Absidia coerulea.
AB  - Steroid 11-hydroxylation by filamentous fungi is a major route for industrial
      scale production of key intermediates in the synthesis of steroid drugs. Although
      it is well established that enzymes involved in fungal hydroxylation of steroids
      are cytochrome P450s (CYP), few fungal steroid hydroxylase genes have been
      identified. In this study, we identified a novel 11alpha-hydroxylase gene
      CYP5311B1 from Absidia coerulea AS3.65 by a combination of transcriptome
      sequencing, real-time qRT-PCR and heterologous expression in Pichia pastoris. The
      full-length open reading frame (ORF) of CYP5311B1 is predicted to encode a CYP
      protein of 527 amino acids whose expression in Pichia cells was confirmed by
      western blot. In addition, the major hydroxylation product was characterized by
      HPLC and 2D NMR. CYP5311B1 was highly induced by steroid substrate at the
      transcriptional level. The cloning and identification of an 11alpha-hydroxylase
      gene from A. coerulea should aid in a better understanding of the structural
      basis underlying regio- and stereoselectivity, and substrate specificity of
      fungal steroid 11alpha-hydroxylases, thus facilitating the engineering of more
      efficient steroid hydroxylases for industrial applications.

PMID- 28428023
TI  - CYP450s analysis across spiny lobster metamorphosis identifies a long sought
      missing link in crustacean development.
AB  - Cytochrome P450s (CYP450s) are a rapidly evolving family of enzymes, making it
      difficult to identify bona fide orthologs with notable lineage-specific
      exceptions. In ecdysozoans, a small number of the most conserved orthologs
      include enzymes which metabolize ecdysteroids. Ecdysone pathway components were
      recently shown in a decapod crustacean but with a notable absence of shade, which
      is important for converting ecdysone to its active form, 20-hydroxyecdysone
      (20HE), suggesting that another CYP450 performs a similar function in
      crustaceans. A CYPome temporal expression analysis throughout metamorphosis
      performed in this research highlights several un-annotated CYP450s displaying
      differential expression and provides information into expression patterns of
      annotated CYP450s. Using the expression patterns in the Eastern spiny lobster
      Sagmariasus verreauxi, followed by 3D modelling and finally activity assays in
      vitro, we were able to conclude that a group of CYP450s, conserved across decapod
      crustaceans, function as the insect shade. To emphasize the fact that these genes
      share the function with shade but are phylogenetically distinct, we name this
      enzyme system Shed.

PMID- 28428024
TI  - Risk factors for severe hypoglycemia in people with insulin-treated diabetes: Are
      we sure we took into account all variables involved?

PMID- 28428025
TI  - Adipokines as atherothrombotic risk factors in obese subjects: Associations with
      haemostatic markers and common carotid wall thickness.
AB  - BACKGROUND AND AIMS: Some crucial associations between obesity-related altered
      adipokine levels and the main factors of atherosclerotic, atherothrombotic
      processes are not fully known. We analysed the relationships of classic
      adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha
      (TNF-alpha), interleukin 6 (IL-6) with the markers of platelet activation,
      including mean platelet volume (MPV), platelet surface/soluble P-selectin,
      platelet-derived microparticles (PMPs), the parameters of coagulation
      abnormalities and common carotid intima-media thickness (IMT) in obese patients
      with or without atherosclerotic comorbidities in comparison to age- and sex
      matched controls. METHODS AND RESULTS: We enrolled 154 obese individuals,
      including 98 suffering from atherosclerotic concomitant conditions, 56 free of
      atherosclerotic comorbidities and 62 healthy controls. Plasma levels of leptin,
      resistin, adiponectin, TNF-alpha, IL-6, soluble P-selectin, and plasminogen
      activator inhibitor-1 antigen (PAI-1 ag) were analysed by ELISA. Platelet surface
      P-selectin and PMPs were measured by flow cytometry. IMT was detected by
      ultrasonography. Adipokines were closely associated with markers of platelet
      hyperactivity, hypercoagulability, hypofibrinolysis and IMT. Significant
      independent associations were found between leptin and platelet count (p <
      0.0001), MPV (p = 0.019), PMPs (p < 0.0001), fibrinogen (p = 0.001), factor VIII
      (FVIII) activity (p = 0.035); adiponectin and PAI-1 ag (p = 0.035); resistin and
      soluble P-selectin (p = 0.002); TNF-alpha and PAI-1 ag (p < 0.0001); and IL-6 and
      fibrinogen (p = 0.011). Finally, leptin (p = 0.0005), adiponectin (p = 0.019), IL
      6 (p = 0.001), MPV (p = 0.0003), PMP (p = 0.008), and FVIII activity (p = 0.043)
      were independent predictors of IMT. CONCLUSION: Overall, we suggest that in obese
      subjects altered adipokine levels play a key role in common carotid
      atherosclerosis both directly and through haemostatic parameters.

PMID- 28428026
TI  - Dietary cyanidin 3-glucoside from purple corn ameliorates doxorubicin-induced
      cardiotoxicity in mice.
AB  - BACKGROUND AND AIMS: Anthracyclines are effective anticancer drugs that have
      improved prognosis of hundred thousand cancer patients worldwide and are
      currently the most common chemotherapeutic agents used for the treatment of
      blood, breast, ovarian and lung cancers. However, their use is limited because of
      a cumulative dose-dependent and irreversible cardiotoxicity that can cause
      progressive cardiomyopathy and congestive heart failure. Aim of the present study
      was to determine the cardioprotective activity of a dietary source of cyanidin 3
      glucoside (C3G), such as purple corn, against doxorubicin (DOX)-induced
      cardiotoxicity in mice. METHODS AND RESULTS: In vitro studies on murine HL-1
      cardiomyocytes showed that pretreatment with both pure C3G and purple corn
      extract improved survival upon DOX treatment. However, C3G and purple corn
      extract did not affect the cytotoxic effect of DOX on human cancer cell lines. We
      then validated in vivo the protective role of a C3G-enriched diet against DOX
      induced cardiotoxicity by comparing the effect of dietary consumption of corn
      isogenic lines with high levels of anthocyanins (purple corn - Red diet - RD) or
      without anthocyanins (yellow corn - Yellow diet - YD) incorporated in standard
      rodent diets. Results showed that mice fed RD survived longer than mice fed YD
      upon injection of a toxic amount of DOX. In addition, ultrastructural analysis of
      hearts from mice fed RD showed reduced histopathological alterations. CONCLUSION:
      Dietary intake of C3G from purple corn protects mice against DOX-induced
      cardiotoxicity.

PMID- 28428028
TI  - Correlation between serum uric acid levels and residual platelet reactivity in
      patients undergoing PCI.

PMID- 28428027
TI  - Fructose intervention for 12 weeks does not impair glycemic control or incretin
      hormone responses during oral glucose or mixed meal tests in obese men.
AB  - BACKGROUND AND AIMS: Incretin hormones glucagon-like peptide (GLP)-1 and glucose
      dependent insulinotropic polypeptide (GIP) are affected early on in the
      pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies
      consistently link high fructose consumption to insulin resistance but whether
      fructose consumption impairs the incretin response remains unknown. METHODS AND
      RESULTS: As many as 66 obese (BMI 26-40 kg/m2) male subjects consumed fructose
      sweetened beverages containing 75 g fructose/day for 12 weeks while continuing
      their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral
      glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a
      mixed meal test before and after fructose intervention. Fructose intervention did
      not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses
      during OGTT and fat-rich meal were unchanged. Postprandial TG response increased
      significantly, p = 0.004, and we observed small but significant increases in
      weight and liver fat content, but not in visceral or subcutaneous fat depots.
      However, even the subgroups who gained weight or liver fat during fructose
      intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A
      minor increase in GIP response during OGTT occurred in subjects who gained liver
      fat (p = 0.049). CONCLUSION: In obese males with features of metabolic syndrome,
      12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or
      GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal.
      Therefore, fructose intake, even accompanied with mild weight gain, increases in
      liver fat and worsening of postprandial TG profile, does not impair glucose
      tolerance or gut incretin response to oral glucose or mixed meal challenge.

PMID- 28428029
TI  - Relationship between high white blood cell count and insulin resistance (HOMA-IR)
      in Korean children and adolescents: Korean National Health and Nutrition
      Examination Survey 2008-2010.
AB  - BACKGROUND AND AIMS: Increasing evidence has indicated that insulin resistance is
      associated with inflammation. However, few studies have investigated the
      association between white blood cell (WBC) count and insulin resistance, as
      measured by a homeostasis model assessment of insulin resistance (HOMA-IR) in a
      general pediatric population. This study aimed to examine the association between
      WBC count and insulin resistance as measured by HOMA-IR in a nationally
      representative sample of children and adolescents. METHODS AND RESULTS: In total,
      2761 participants (1479 boys and 1282 girls) aged 10-18 years were selected from
      the 2008-2010 Korean National Health and Nutrition Examination Survey. Insulin
      resistance was defined as a HOMA-IR value greater than the 90th percentile. The
      odds ratios and 95% confidence intervals for insulin resistance were determined
      using multiple logistic regression analysis. The mean values of most
      cardiometabolic variables tended to increase proportionally with WBC count
      quartiles. The prevalence of insulin resistance significantly increased in
      accordance with WBC count quartiles in both boys and girls. Compared to
      individuals in the lowest WBC count quartile, the odds ratio for insulin
      resistance for individuals in the highest quartile was 2.84 in boys and 3.20 in
      girls, after adjusting for age, systolic blood pressure, body mass index, and
      waist circumference. CONCLUSION: A higher WBC count was positively associated
      with an increased risk of insulin resistance in Korean children and adolescents.
      This study suggests that WBC count could facilitate the identification of
      children and adolescents with insulin resistance.

PMID- 28428030
TI  - Complement inhibition with eculizumab for thrombotic microangiopathy rescues a
      living-donor kidney transplant in a patient with antiphospholipid antibody
      syndrome.
AB  - Antiphospholipid antibody syndrome (APS) is an enigmatic heterogeneous disorder
      despite several revelations in its pathobiology. Renal transplantation in
      patients with APS has been notoriously difficult due to the high risk of
      development of thrombotic microangiopathy (TMA), which is often refractory to
      conventional treatment modalities such as aggressive anticoagulation and
      plasmapheresis. We describe a case of a 58-year-old male with secondary APS
      undergoing living unrelated renal transplantation for end-stage renal disease
      from lupus nephritis. Shortly after transplantation, he developed graft
      dysfunction from APS related TMA that was refractory to systemic anticoagulation
      and plasmapheresis. After becoming hemodialysis dependent, the patient was
      started on eculizumab, a humanized monoclonal antibody against complement factor
      5, as salvage therapy. We show that this intervention successfully rescued his
      renal allograft and that the patient has remained dialysis free for over 20
      months. Our experience adds to the limited body of literature suggesting the role
      of complement inhibition in facilitating renal transplantation in patients with
      APS spectrum of disorders, thus adding a new tool to the therapeutic
      armamentarium for this difficult disease. The optimal treatment schedule and long
      term safety data for eculizumab in complement mediated TMA is still unclear. The
      search for an optimal biomarker to help guide treatment duration is an area of
      active research.

PMID- 28428031
TI  - The effect of hypoxia preconditioning on the neural and stemness genes expression
      profiling in human umbilical cord blood mesenchymal stem cells.
AB  - In recent years, human umbilical cord blood-derived mesenchymal stem cell (hUB
      MSCs) has been regarded as an alternative source for stem cell therapy. In this
      study, we evaluated the effect of hypoxia preconditioning (HPC) on the expression
      of Nt-3, GFAP, Nestin, Oct-4 and Nanog genes and proliferative capacity of hUB
      MSCs in comparison with normoxic conditions. HPC+Hypoxia protocol includes
      cultured hUB-MSCs for 15min at 2.5% O2 and after that reoxygenation for 30min at
      21% O2 (HPC), and then hypoxia preconditioned hUB-MSCs subjected to 2.5% O2 for
      72h (Hypoxia). Conclusively, the results showed that hypoxic preconditioning is
      an effective strategy for enhancing proliferation capacity of hUB-MSCs, and also
      can trigger expression of some of the neural genes. In addition, the concept of
      involvement of oxygen tension in the expression of some of the neural genes of
      hUB-MSCs would be a good sign of enhanced neural differentiation potential in
      vitro.

PMID- 28428032
TI  - Does semi-automatic bone-fragment segmentation improve the reproducibility of the
      Letournel acetabular fracture classification?
AB  - BACKGROUND: The Letournel classification of acetabular fracture shows poor
      reproducibility in inexperienced observers, despite the introduction of 3D
      imaging. We therefore developed a method of semi-automatic segmentation based on
      CT data. The present prospective study aimed to assess: (1) whether semi
      automatic bone-fragment segmentation increased the rate of correct
      classification; (2) if so, in which fracture types; and (3) feasibility using the
      open-source itksnap 3.0 software package without incurring extra cost for users.
      HYPOTHESIS: Semi-automatic segmentation of acetabular fractures significantly
      increases the rate of correct classification by orthopedic surgery residents.
      METHODS: Twelve orthopedic surgery residents classified 23 acetabular fractures.
      Six used conventional 3D reconstructions provided by the center's radiology
      department (conventional group) and 6 others used reconstructions obtained by
      semi-automatic segmentation using the open-source itksnap 3.0 software package
      (segmentation group). Bone fragments were identified by specific colors. Correct
      classification rates were compared between groups on Chi2 test. Assessment was
      repeated 2 weeks later, to determine intra-observer reproducibility. RESULTS:
      Correct classification rates were significantly higher in the "segmentation"
      group: 114/138 (83%) versus 71/138 (52%); P<0.0001. The difference was greater
      for simple (36/36 (100%) versus 17/36 (47%); P<0.0001) than complex fractures
      (79/102 (77%) versus 54/102 (53%); P=0.0004). Mean segmentation time per fracture
      was 27+/-3min [range, 21-35min]. The segmentation group showed excellent intra
      observer correlation coefficients, overall (ICC=0.88), and for simple (ICC=0.92)
      and complex fractures (ICC=0.84). CONCLUSION: Semi-automatic segmentation,
      identifying the various bone fragments, was effective in increasing the rate of
      correct acetabular fracture classification on the Letournel system by orthopedic
      surgery residents. It may be considered for routine use in education and
      training. LEVEL OF EVIDENCE: III: prospective case-control study of a diagnostic
      procedure.

PMID- 28428033
TI  - A critical analysis of limb symmetry indices of hop tests in athletes after
      anterior cruciate ligament reconstruction: A case control study.
AB  - BACKGROUND: Hop tests are frequently used to determine return to sports (RTS)
      after anterior cruciate ligament reconstruction (ACLR). Given that bilateral
      deficits are present after ACLR, this may result in a falsely high limb symmetry
      index (LSI), since LSI is calculated as a ratio between the values of the limbs.
      HYPOTHESIS: Athletes after ACLR would achieve LSI>90% for the hop test. Secondly,
      athletes after ACLR demonstrate decreased jump distance on the single hop for
      distance (SLH) and triple leg hop for distance (TLH) and decreased number of hops
      for the side hop (SH) for both involved and uninvolved limbs compared to
      normative data of sex, age and type of sports matched healthy athletes. MATERIALS
      AND METHODS: Fifty-two patients (38 males mean age 23.9+/-3.5years; 14 females
      mean age 21.7+/-3.5 years) who had undergone an ACLR participated in this study.
      Patients performed the 3 hop tests at a mean time of 7 months after ACLR. Hop
      distance, number of side hops and LSI were compared with normative data of 188
      healthy athletes. RESULTS: The differences between the involved limb and the
      uninvolved limb were significant in all hop tests (SLH P=0.003, TLH P=0.003, SH
      P=0.018). For females, only significant between limb differences were found in
      the SLH (P=0.049). For both the SLH and the TLH, significant differences were
      found between the involved limb and the normative data (males; SLH P<0.001, TLH
      P<0.001; females; SLH P<0.001, TLH P=0.006) and between the uninvolved limb and
      the normative data for both males and females (males; SLH P<0.001, TLH P<0.001;
      females; SLH P=0.003, TLH P=0.038). For the SH, only significant differences were
      found between the involved limb and the normative values in males (P=0.033).
      CONCLUSION: Athletes who have undergone an ACLR demonstrate bilateral deficits on
      hop tests in comparison to age and sex matched normative data of healthy
      controls. Using the LSI may underestimate performance deficits and should
      therefore be analyzed with caution when used as a criterion for RTS after ACLR.
      LEVEL OF EVIDENCE: III, case control study.

PMID- 28428034
TI  - Near-anatomical correction using a CT-guided technique of a forearm malunion in a
      15-year-old girl: A case report including surgical technique.
AB  - BACKGROUND: In this case report, we describe a left-arm both-bone forearm
      fracture in a 15-year-old girl who fell off a swing. Conservative treatment with
      an above-elbow cast failed, resulting in a malunion with functional impairment.
      The pro- and supination were 90/0/10, respectively. The patient complained of
      difficulties performing daily activities. For this pediatric case, a corrective
      osteotomy was proposed using a CT-guided technique aiming for maximum anatomical
      and functional outcome. It was the first time this technique was used in our
      hospital. METHODS: A corrective osteotomy of the patient's left arm was performed
      using 3D printed templates to guide the osteotomy orientation. These templates
      were produced using specialized software in which CT images of her malunited left
      forearm were overlaid with the mirrored images of her healthy right forearm.
      RESULTS: The postoperative CT-scan showed a near-anatomical reduction with close
      to 1 degrees  correction in all three planes, as compared to the preoperative
      planning. Three months after surgery, the patient had regained full function of
      her left forearm. CONCLUSION: Although this was the first time this technique was
      used in our hospital, it resulted in excellent anatomical and functional outcomes
      making it a safe, reliable and precise treatment option that may be useful for
      even more complex corrections. LEVEL OF EVIDENCE: Level V.

PMID- 28428035
TI  - Evaluation of the external fixator TrueLok Hexapod System for tibial deformity
      correction in children.
AB  - BACKGROUND: Tibial deformities are common in paediatric orthopaedic practice.
      Correcting multiplanar tibial deformities associated with lower limb length
      discrepancy can be challenging. Hexapod external fixation with gradual correction
      has been proven effective in this situation. OBJECTIVE: To assess clinical and
      radiological outcomes of gradual tibial deformity correction using the external
      fixator TL-HEXTM (Orthofix) in children. HYPOTHESIS: TL-HEXTM is effective in
      correcting tibial deformities in children. PATIENTS AND METHODS: This multicentre
      retrospective study collected data from the medical files of 26 patients with 31
      tibial deformities treated by gradual correction using TL-HEXTM. The tibial
      deformities were due to congenital defects in 11 (35%) cases, Blount's disease in
      9 (29%) cases, pseudo-achondroplasia in 4 (13%) cases, and other causes in 7
      (23%) cases. Mean age at surgery was 11.9 years. In each patient, antero
      posterior long leg radiographs obtained pre-operatively and at last follow-up
      were used to measure parameters including the mechanical axis deviation (MAD),
      medial proximal tibia angle (MPTA), and leg length discrepancy (LLD). RESULTS:
      The mean healing index was 39.3 days/cm (range, 32-58 days/cm). The overall
      complication rate was 61%, with 11 unplanned visits. Superficial pin tract
      infection was the most common complication. Significant decreases between the pre
      operative and post-operative assessments occurred in mean MAD (from 32.1mm to
      10.2mm, P<0.001) and mean LLD (from 36.8mm to 9.1mm, P<0.001). Patients who
      underwent proximal tibial osteotomy had a significant improvement in MPTA, from
      80.6 degrees  to 88.5 degrees  (P=0.006). DISCUSSION: This is the first clinical
      study specifically designed to assess outcomes of TL-HEXTM limb lengthening and
      deformity correction. MAD, MPTA, and LLD were significantly improved at last
      follow-up. MAD was greater than 10mm at last follow-up in only 11patients. The
      complication rate was similar to those reported with other external fixators. TL
      HEXTM is effective in the management of tibial deformities in children. LEVEL OF
      EVIDENCE: IV (retrospective study).

PMID- 28428036
TI  - Giant cell tumor of tendon sheath: Open surgery or arthroscopic synovectomy? A
      systematic review of the literature.
AB  - PURPOSE: Giant cell tumor of tendon sheath (GCTTS), formerly known as pigmented
      villonodular synovitis (PVNS), is a benign, locally aggressive, proliferative
      disorder of the synovium involving a joint, bursa, or tendon sheath. Treatment of
      GCTTS involves early surgical resection to limit articular destruction and the
      risk of recurrence. Synovectomy remains the treatment of choice for GCTTS, but
      without clear consensus to make an open or arthroscopic synovectomy and no
      certainty on the responsibility of surgery in the evolution towards the
      degenerative osteoarthritis. The aim of this study was to evaluate the long-term
      clinical outcomes and the rate of recurrence of open or arthroscopic excision of
      GCTTS of the four most frequently involved joints: the shoulder, hip, knee and
      ankle. METHODS: We performed a systematic review of literature in September 2015.
      The keywords were "villonodular synovitis" AND "surgical treatment". The two
      authors analyzed 413 articles, according to title and abstract. Forty articles
      were selected, read entirely and references were analyzed. RESULTS: Thirty-three
      articles were selected. CONCLUSION: Our review of literature showed that
      arthroscopic excision is effective for localized type of GCTTS for all four
      joints. In diffuse type GCTTS, the efficacy of arthroscopic synovectomy has only
      been shown for the knee joint. In the other joints, early diagnosis can improve
      clinical outcomes, but we cannot certify that surgical treatment avoids
      osteoarthritis degradation. STUDY DESIGN: Review of literature, level of evidence
      IV.

PMID- 28428037
TI  - Non-operative treatment of displaced distal radius fractures leads to acceptable
      functional outcomes, however at the expense of 40% subsequent surgeries.
AB  - BACKGROUND: Although secondary displacement following closed reduction and
      plaster immobilisation is high, several guidelines still recommend non-operative
      treatment for displaced distal radius fractures with an adequate closed
      reduction. PURPOSE: The purpose of this study was to evaluate functional
      outcomes, measured with the Disability of the Arm, Shoulder and Hand (DASH)
      questionnaire, in non-operative treated patients with displaced distal radius
      fractures and an adequate closed reduction confirmed on radiograph. MATERIALS AND
      METHODS: From a retrospective database, we reviewed non-operative treated adult
      patients with an unilateral displaced distal radius fracture and adequate closed
      reduction confirmed on radiograph. The primary outcome was the DASH score at
      12months. DASH scores were prospectively collected pre-trauma and at three, six
      and 12months. Secondary outcome was the number of subsequent surgeries due to
      secondary displacement or a symptomatic malunion, and their possible predictors.
      Additionally, the difference in DASH scores between patients who were treated due
      to secondary displacement and asymptomatic malunion was compared. RESULTS: One
      hundred and sixteen patients were included. The median age was 62 years and 79%
      was female. Fractures were classified according to the AO/OTA classification as
      follows: AO/OTA type A (49%), AO/OTA type B (3%), AO/OTA type C (48%). After
      12months the median DASH score was 15. Forty-six (40%) patients underwent
      subsequent surgery due to a secondary displacement or symptomatic malunion. No
      significant differences in DASH scores between patients who were treated non
      operatively and patients who received subsequent surgery were found. Younger
      patients were more likely to undergo subsequent surgery. Patients with a
      symptomatic malunion had significant higher DASH scores compared to patients with
      secondary displacement. DISCUSSION: Non-operative treatment of displaced distal
      radius fractures after adequate closed reduction confirmed on radiograph leads to
      acceptable functional outcomes after 12months, however, at the expense of 40%
      subsequent surgeries. LEVEL OF EVIDENCE: Level IV, retrospective cohort study.

PMID- 28428038
TI  - Non-invasive tracking of hydrogel degradation using upconversion nanoparticles.
AB  - : Tracking the distribution and degradation of hydrogels in vivo is important for
      various applications including tissue engineering and drug delivery. Among
      various imaging modalities, fluorescence imaging has attracted intensive
      attention due to their high sensitivity, low cost and easy operation.
      Particularly, upconversion nanoparticles (UCNPs) that emit visible lights upon
      near-infrared (NIR) light excitation as tracking probes are promising in
      deciphering the fate of hydrogels after transplantation. Herein, we reported a
      facile and non-invasive in vivo hydrogel tracking method using UCNPs, where the
      degradation of hydrogels was determined using the decrease in fluorescence
      intensity from the UCNPs encapsulated in the hydrogels. We found that the change
      in the fluorescence intensity from the UCNPs was well consistent with that of the
      fluorescein isothiocyanate (FITC) covalently conjugated to hydrogels and also
      with the weight change of the hydrogels, suggesting the accuracy of the UCNPs in
      tracking the degradation of hydrogels. Furthermore, the in vivo fluorescence
      signals were only observed from the UCNPs instead of FITC after implantation for
      7days due to the deep tissue penetration of UCNPs, demonstrating the capability
      of UCNPs in longitudinal, consecutive and non-invasive monitoring the in vivo
      degradation of hydrogels without causing any damage to the major organs (heart,
      lung, liver and kidney) of model rats. This study thus paves the way for
      monitoring the in vivo behaviors of biomimetic materials via deep tissue imaging
      with great clinical translation potentials. STATEMENT OF SIGNIFICANCE: Long-term
      noninvasive in vivo tracking of the distribution and degradation of biodegradable
      hydrogels using fluorescent probes is important in tissue regeneration and drug
      delivery. Unlike the widely used fluorescent dyes and quantum dots (QDs) that
      suffer from photobleaching and undesired toxicity, upconversion nanoparticles
      (UCNPs) with high stability, deep tissue penetration as tracking probes are
      promising in deciphering the fate of hydrogels after transplantation. Herein, we
      reported a noninvasive in vivo hydrogel tracking method using UCNPs and found
      that the fluorescence intensity change from the UCNPs was well consistent with
      the weight change of the hydrogels, suggesting the accuracy of UCNPs in tracking
      hydrogel degradation. This study provides inspirations on developing advanced NIR
      light regulated probes with great clinical translation potentials.

PMID- 28428039
TI  - Antimicrobial mechanism of epigallocatechin gallate and gallocatechin gallate:
      They target 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the key enzyme of
      the MEP terpenoid biosynthetic pathway.
AB  - The catechins EGCG and GCG show a variety of pharmacological activities,
      especially an antibacterial capacity, but their modes of antimicrobial action
      have not been fully elucidated. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase
      (DXR), the first key enzyme in the MEP pathway for terpenoid biosynthesis, is a
      recently validated antimicrobial target. In order to disclose the antibacterial
      mechanism of EGCG and GCG, the DXR inhibitory activity of them was investigated
      in this study. The data show that EGCG and GCG both could specifically suppress
      the activity of DXR, with EGCG exhibiting relatively low effect against DXR (IC50
      about 210 MUM) and GCG displaying strong activity (IC50 27.5 MUM). In addition,
      studies on inhibition kinetics of the catechins against DXR demonstrate that they
      are competitive inhibitors of DXR against DXP and uncompetitive inhibitors with
      respect to NADPH. Meanwhile, the possible interactions between DXR and the
      catechine, esyth onlols were simulated via docking experiments.

PMID- 28428040
TI  - Design, synthesis, and docking studies of quinazoline analogues bearing aryl
      semicarbazone scaffolds as potent EGFR inhibitors.
AB  - Two series of quinazoline derivatives bearing aryl semicarbazone scaffolds (9a-o
      and 10a-o) were designed, synthesized and evaluated for the IC50 values against
      four cancer cell lines (A549, HepG2, MCF-7 and PC-3). The selected compound 9o
      was further evaluated for the inhibitory activity against EGFR kinases. Four of
      the compounds showed excellent cytotoxicity activity and selectivity with the
      IC50 values in single-digit MUM to nanomole range. Two of them are equal to more
      active than positive control afatinib against one or more cell lines. The most
      promising compound 9o showed the best activity against A549, HepG2, MCF-7 and PC
      3 cancer cell lines and EGFR kinase, with the IC50 values of 1.32+/-0.38MUM,
      0.07+/-0.01MUM, 0.91+/-0.29MUM and 4.89+/-0.69MUM, which were equal to more
      active than afatinib (1.40+/-0.83MUM, 1.33+/-1.28MUM, 2.63+/-1.06MUM and 3.96+/
      0.59MUM), respectively. Activity of the most promising compound 9o (IC50 56nM)
      against EGFR kinase was slightly lower to the positive compound afatinib (IC50
      1.6nM) but more active than reference staurosporine (IC50 238nM). The result of
      flow cytometry, with the dose of compound 9o increasing, which indicated the
      compound 9o could induce remarkable apoptosis of A549 and cells in a dose
      dependent manner. Structure-activity relationships (SARs) and docking studies
      indicated that replacement of the cinnamamide group by aryl semicarbazone
      scaffolds slightly decreased the anti-tumor activity. The results suggested that
      hydroxy substitution at C-4 had a significant impact on the activity and
      replacement of the tetrahydrofuran group by methyl moiety was not beneficial for
      the activity.

PMID- 28428041
TI  - Structure of a Myeloid cell leukemia-1 (Mcl-1) inhibitor bound to drug site 3 of
      Human Serum Albumin.
AB  - Amplification of the gene encoding Myeloid cell leukemia-1 (Mcl-1) is one of the
      most common genetic aberrations in human cancer and is associated with high tumor
      grade and poor survival. Recently, we reported on the discovery of high affinity
      Mcl-1 inhibitors that elicit mechanism-based cell activity. These inhibitors are
      lipophilic and contain an acidic functionality which is a common chemical profile
      for compounds that bind to albumin in plasma. Indeed, these Mcl-1 inhibitors
      exhibited reduced in vitro cell activity in the presence of serum. Here we
      describe the structure of a lead Mcl-1 inhibitor when bound to Human Serum
      Albumin (HSA). Unlike many acidic lipophilic compounds that bind to drug site 1
      or 2, we found that this Mcl-1 inhibitor binds predominantly to drug site 3. Site
      3 of HSA may be able to accommodate larger, more rigid compounds that do not fit
      into the smaller drug site 1 or 2. Structural studies of molecules that bind to
      this third site may provide insight into how some higher molecular weight
      compounds bind to albumin and could be used to aid in the design of compounds
      with reduced albumin binding.

PMID- 28428042
TI  - Synthesis and biological evaluation of selective tubulin inhibitors as anti
      trypanosomal agents.
AB  - African trypanosomiasis is still a threat to human health due to the severe side
      effects of current drugs. We identified selective tubulin inhibitors that showed
      the promise to the treatment of this disease, which was based on the tubulin
      protein structural difference between mammalian and trypanosome cells. Further
      lead optimization was performed in the current study to improve the efficiency of
      the drug candidates. We used Trypanosoma brucei brucei cells as the parasite
      model, and human normal kidney cells and mouse macrophage cells as the host model
      to evaluate the compounds. One new analog showed great potency with an IC50 of
      70nM to inhibit the growth of trypanosome cells and did not affect the viability
      of mammalian cells. Western blot analyses reveal that the compound decreased
      tubulin polymerization in T. brucei cells. A detailed structure activity
      relationship (SAR) was summarized that will be used to guide future lead
      optimization.

PMID- 28428043
TI  - Effects of bone marrow on the microenvironment of the human pancreatic islet: A
      Protein Profile Approach.
AB  - Stem cells are a new therapeutic modality that may support the viability and
      function of human organs and tissue. Our previous studies have revealed that
      human allogeneic bone marrow (BM) sustains pancreatic beta cell function and
      survival. This paper examines whether BM creates a microenvironment that supports
      human pancreatic islets in vitro by evaluating 107 proteins in culture media from
      BM, islet, and islet/bone marrow (IB) with mass spectrometry. Proteins were
      considered up- or down-regulated if p-values < 0.05 and fold change was greater
      than 2 fold I VS. IB. In addition, proteins identified that were uniquely found
      in islets co-cultured with bone marrow, but not in islets or bone marrow. A 95%
      protein probability was used as a threshold. Twenty three proteins were
      upregulated, and sixteen proteins were downregulated. The function of each
      protein is listed based on the protein database, which include structural
      proteins (9 upregulated, 4 downregulated); anti-protease and anti-endopeptidase
      enzymes (8 upregulated); cation binding proteins (6 up-regulated). Six proteins
      were uniquely identified in islet co-cultured with bone marrow. Three are anti
      proteases or anti-endopeptidases, and 1 is a structural protein. These findings
      suggest that BM, by changing culture media proteins, may be one of mechanisms to
      maintain human islet function and survival.

PMID- 28428044
TI  - Transcriptional co-activator YAP regulates cAMP signaling in Sertoli cells.
AB  - FSH mediated cyclic AMP (cAMP) signaling is crucial for function of testicular
      Sertoli cells (Sc) during puberty. Yes-kinase Associated Protein (YAP), a
      transcriptional co-activator, regulates cell proliferation and differentiation.
      However, its role in testicular function is not known. In present study, we have
      identified YAP as an important regulator of cAMP signaling in Sc, in-vitro.
      Verteporfin, a YAP-inhibitor, down regulated the expression of cAMP responsive
      genes necessary for spermatogenesis in Sc. Action of forskolin, which acts via
      cAMP, was also antagonized by verteporfin, limiting expression of these genes.
      Assessment of cAMP-responsive-element-binding-protein (CREB) phosphorylation
      revealed that verteporfin augmented the phosphorylation of CREB at Ser133
      residue. This effect of verteporfin on CREB phosphorylation was attenuated by H
      89, the PKA inhibitor. This clearly suggested involvement of PKA in verteporfin
      mediated CREB phosphorylation. We provided evidence for the first time that YAP
      modulates cAMP signaling in Sc which may be critical for testicular function.

PMID- 28428046
TI  - Cryoprotectants: A review of the actions and applications of cryoprotective
      solutes that modulate cell recovery from ultra-low temperatures.
AB  - Cryopreservation has become a central technology in many areas of clinical
      medicine, biotechnology, and species conservation within both plant and animal
      biology. Cryoprotective agents (CPAs) invariably play key roles in allowing cells
      to be processed for storage at deep cryogenic temperatures and to be recovered
      with high levels of appropriate functionality. As such, these CPA solutes possess
      a wide range of metabolic and biophysical effects that are both necessary for
      their modes of action, and potentially complicating for cell biological function.
      Early successes with cryopreservation were achieved by empirical methodology for
      choosing and applying CPAs. In recent decades, it has been possible to assemble
      objective information about CPA modes of action and to optimize their application
      to living systems, but there still remain significant gaps in our understanding.
      This review sets out the current status on the biological and chemical knowledge
      surrounding CPAs, and the conflicting effects of protection versus toxicity
      resulting from the use of these solutes, which are often required in molar
      concentrations, far exceeding levels found in normal metabolism. The biophysical
      properties of CPAs that allow them to facilitate different approaches to
      cryogenic storage, including vitrification, are highlighted. The topics are
      discussed with reference to the historical background of applying CPAs, and the
      relevance of cryoprotective solutes in natural freeze tolerant organisms.
      Improved cryopreservation success will be an essential step in many future areas
      such as regenerative medicine, seed banking, or stem cell technology. To achieve
      this, we will need to further improve our understanding of cryobiology, where
      better and safer CPAs will be key requirements.

PMID- 28428045
TI  - Sco2 deficient mice develop increased adiposity and insulin resistance.
AB  - Cytochrome c oxidase (COX) is an essential transmembrane protein complex (Complex
      IV) in the mitochondrial respiratory electron chain. Mutations in genes
      responsible for the assembly of COX are associated with Leigh syndrome,
      cardiomyopathy, spinal muscular atrophy and other fatal metabolic disorders in
      humans. Previous studies have shown that mice lacking the COX assembly protein
      Surf1 (Surf1-/- mice) paradoxically show a number of beneficial metabolic
      phenotypes including increased insulin sensitivity, upregulation of mitochondrial
      biogenesis, induction of stress response pathways and increased lifespan. To
      determine whether these effects are specific to the Surf1 mutation or a more
      general effect of reduced COX activity, we asked whether a different mutation
      causing reduced COX activity would have similar molecular and physiologic
      changes. Sco2 knock-in/knock-out (KI/KO) mice in which one allele of the Sco2
      gene that encodes a copper chaperone required for COX activity is deleted and the
      second allele is mutated, have previously been shown to be viable despite a 30
      60% reduction in COX activity. In contrast to the Surf1-/- mice, we show that
      Sco2 KI/KO mice have increased fat mass, associated with reduced beta-oxidation
      and increased adipogenesis markers, reduced insulin receptor beta (IR-beta levels
      in adipose tissue, reduced muscle glucose transporter 4 (Glut4) levels and a
      impaired response to the insulin tolerance test consistent with insulin
      resistance. COX activity and protein are reduced approximately 50% in adipose
      tissue from the Sco2 KI/KO mice. Consistent with the increase in adipose tissue
      mass, the Sco2 KI/KO mice also show increased hepatosteatosis, elevated serum and
      liver triglyceride and increased serum cholesterol levels compared to wild-type
      controls. In contrast to the Surf1-/- mice, which show increased mitochondrial
      number, upregulation of the mitochondrial unfolded protein response (UPRMT)
      pathway and no significant change in mitochondrial respiration in several
      tissues, Sco2 KI/KO mice do not upregulate the UPRMT, and tissue oxygen
      consumption and levels of several proteins involved in mitochondrial function are
      reduced in adipose tissue compared to wild type mice. Thus, the metabolic effects
      of the Sco2 and Surf1-/- mutations are opposite, despite comparable changes in
      COX activity, illuminating the complex impact of mitochondrial dysfunction on
      physiology and pointing to an important role for complex IV in regulating
      metabolism.

PMID- 28428047
TI  - Diffusion MRI of the human brain at ultra-high field (UHF): A review.
AB  - The continued drive towards MRI scanners operating at increasingly higher main
      magnetic fields is primarily motivated by the maxim that more teslas mean more
      signal and lead to better images. This promise of increased signal, which cannot
      easily be achieved in other ways, encourages efforts to overcome the inextricable
      technical challenges which accompany this endeavor. Unlike for many applications,
      however, diffusion imaging is not currently able to directly reap these potential
      signal gains - at the time of writing it seems fair to say that, for matched
      gradient and RF hardware, the majority of diffusion images acquired at 7T, while
      comparable in quality to those achievable at 3T, do not demonstrate a clear
      advantage over what can be obtained at lower field. This does not mean that
      diffusion imaging at UHF is not a worthwhile pursuit - but more a reflection of
      the fact that the associated challenges are manifold - and converting the
      potential of higher field strengths into 'better' diffusion imaging is by no
      means a straightforward task. This article attempts to summarize the specific
      reasons that make diffusion imaging at UHF more complicated than one might
      expect, and to highlight the range of developments that have already been made
      which have enabled diffusion images of excellent quality to be acquired at 7T.

PMID- 28428048
TI  - Multi-center machine learning in imaging psychiatry: A meta-model approach.
AB  - One of the biggest problems in automated diagnosis of psychiatric disorders from
      medical images is the lack of sufficiently large samples for training. Sample
      size is especially important in the case of highly heterogeneous disorders such
      as schizophrenia, where machine learning models built on relatively low numbers
      of subjects may suffer from poor generalizability. Via multicenter studies and
      consortium initiatives researchers have tried to solve this problem by combining
      data sets from multiple sites. The necessary sharing of (raw) data is, however,
      often hindered by legal and ethical issues. Moreover, in the case of very large
      samples, the computational complexity might become too large. The solution to
      this problem could be distributed learning. In this paper we investigated the
      possibility to create a meta-model by combining support vector machines (SVM)
      classifiers trained on the local datasets, without the need for sharing medical
      images or any other personal data. Validation was done in a 4-center setup
      comprising of 480 first-episode schizophrenia patients and healthy controls in
      total. We built SVM models to separate patients from controls based on three
      different kinds of imaging features derived from structural MRI scans, and
      compared models built on the joint multicenter data to the meta-models. The
      results showed that the combined meta-model had high similarity to the model
      built on all data pooled together and comparable classification performance on
      all three imaging features. Both similarity and performance was superior to that
      of the local models. We conclude that combining models is thus a viable
      alternative that facilitates data sharing and creating bigger and more
      informative models.

PMID- 28428049
TI  - Stem Cells for Retinal Disease: A Perspective on the Promise and Perils.
AB  - PURPOSE: To summarize key concepts, as well as early safety and efficacy signals
      from clinical trials, for stem/progenitor cell-based interventions for retinal
      disease. DESIGN: Interpretive essay. METHODS: Review and synthesis of selected
      recent reports of stem/progenitor cell-based approaches for retinal disease, with
      interpretation and perspective. RESULTS: Stem/progenitor cell-based interventions
      represent a novel class of potential therapies for retinal diseases, such as age
      related macular degeneration and inherited retinal dystrophies, aoong others.
      Sources include pluripotent stem cells and fetal and postnatal tissues. Two
      mechanisms of "rescue" have been proposed: regenerative or trophic. Although
      pluripotent and fetal sourced-cell types have been tested in preclinical animal
      models of retinal disease, many postnatal stem/progenitor cell populations
      currently in trial do not have preclinical safety or efficacy data. Some early
      phase trials of cell therapies suggest acceptable safety profiles. Other reports,
      involving some types of autologous, nonocular cell sources, have been linked to
      severe, blinding complications. Larger trials will be needed to determine short
      term and long-term safety and efficacy of these cell-based interventions.
      CONCLUSIONS: Stem/progenitor cell-based interventions have the potential to
      address blinding retinal diseases that affect hundreds of millions worldwide. Yet
      no Food and Drug Administration-approved stem cell therapies for retinal disease
      exist. Although some early-phase trial data are promising, reports of blinding
      complications from cell interventions remain troubling. It is paramount to apply
      a strong level of scientific rigor toward a well-planned, step-wise sequence of
      preclinical and clinical studies, to determine whether this class of potential
      therapies will be safe and effective for individuals with retinal diseases.

PMID- 28428050
TI  - Socioeconomic Disparity in Global Burden of Cataract: An Analysis for 2013 With
      Time Trends Since 1990.
AB  - PURPOSE: To assess socioeconomic disparity in global burden of cataract, by using
      disability-adjusted life years (DALYs). DESIGN: International, comparative burden
      of-disease study. METHODS: Published data on national age-standardized DALY rates
      caused by cataract and human development index (HDI) between 1990 and 2013 were
      obtained. The association between age-standardized DALY rates and HDI in 2013 was
      analyzed. The health-related Gini coefficients and the concentration indexes were
      calculated to explore the trends in between-country inequality in cataract burden
      from 1990 to 2013. RESULTS: Multiple comparison revealed that lower-HDI countries
      had higher age-standardized DALY rates caused by cataract. Age-standardized DALY
      rates were inversely associated with HDI (beta = -0.522, P < .01). From 1990 to
      2013, global age-standardized DALY rates showed a trend of decline, whereas the
      Gini coefficients increased from 0.409 to 0.439. The concentration indexes
      indicated that socioeconomic-associated inequality declined in the 1990s and
      subsequently increased since 2000, with values of -0.259 in 1990, -0.244 in 2000,
      and -0.273 in 2013. CONCLUSIONS: Global health progress in cataract was
      accompanied by widening inequality, with cataract burden being more concentrated
      in countries with lower socioeconomic status. The findings highlight the need to
      provide more cataract services for developing countries, to combat global vision
      loss caused by cataract.

PMID- 28428051
TI  - Cell-penetrating peptide CGKRK mediates efficient and widespread targeting of
      bladder mucosa following focal injury.
AB  - The bladder presents an attractive target for topical drug delivery. The barrier
      function of the bladder mucosa (urothelium) presents a penetration challenge for
      small molecules and nanoparticles. We found that focal mechanical injury of the
      urothelium greatly enhances the binding and penetration of intravesically
      administered cell-penetrating peptide CGKRK (Cys-Gly-Lys-Arg-Lys). Notably, the
      CGKRK bound to the entire urothelium, and the peptide was able to penetrate into
      the muscular layer. This phenomenon was not dependent on intravesical bleeding
      and was not caused by an inflammatory response. CGKRK also efficiently penetrated
      the urothelium after disruption of the mucosa with ethanol, suggesting that loss
      of barrier function is a prerequisite for widespread binding and penetration. We
      further demonstrate that the ability of CGKRK to efficiently bind and penetrate
      the urothelium can be applied toward mucosal targeting of CGKRK-conjugated
      nanogels to enable efficient and widespread delivery of a model payload
      (rhodamine) to the bladder mucosa.

PMID- 28428052
TI  - Opening eyes to nanomedicine: Where we are, challenges and expectations on
      nanotherapy for diabetic retinopathy.
AB  - People affected with ocular diseases will significantly increase over the next
      decades, and, consequently, a substantial increase in health costs is expected.
      Diabetic retinopathy is the most common chronic complication of diabetes. The
      treatment of eye diseases affecting the posterior segment, such as diabetic
      retinopathy, is quite challenging due to the anatomy, physiology and biochemistry
      of the eye. Therefore, the development of new therapeutics for posterior eye
      diseases has been a major focus of pharmaceutical research in the area of vision
      sciences. Several nanosystems already offer efficient solutions for
      ophthalmological conditions, targeting internal eye tissues, as the retina, and
      many novel products are expected to appear hereafter. This review provides an
      insight on nanoparticle-based solutions for therapies directed to posterior
      segment of the eye diseases, particularly diabetic retinopathy, the present
      scenario, and the demands and expectations for the future.

PMID- 28428053
TI  - Discrimination between ulcerative colitis and Crohn's disease using phage display
      identified peptides and virus-mimicking synthetic nanoparticles.

PMID- 28428054
TI  - Modified nanoparticle mediated IL-12 immunogene therapy for colon cancer.
AB  - For the past few years, immunotherapy has recently shown considerable clinical
      benefit in CRC therapy, and the application of immunologic therapies in cancer
      treatments continues to increase perennially. Interleukin-12, an ideal candidate
      for tumor immunotherapy, could activate both innate and adaptive immunities. In
      this study, we developed a novel gene delivery system with a self-assembly method
      by MPEG-PLA and DOTAP(DMP) with zeta-potential value of 38.5mV and size of
      37.5nm. The supernatant of lymphocytes treated with supernatant from Ct26
      transfected pIL12 with DMP could inhibit Ct26 cells growth ex vivo. Treatment of
      tumor-bearing mice with DMP-pIL12 complex has significantly inhibited tumor
      growth at both the subcutaneous and peritoneal model in vivo by inhibiting
      angiogenesis, promoting apoptosis and reducing proliferation. The IL-12 plasmid
      and DMP complex may be used to treat the colorectal cancer in clinical as a new
      drug.

PMID- 28428056
TI  - Recent development of synthetic nonviral systems for sustained gene delivery.
AB  - Sustained gene delivery is of particular importance today because it circumvents
      the need for repeated therapeutic administration and provides spatial and
      temporal control of the release profile. Better understanding of the genetic
      basis of diseases and advances in gene therapy have propelled significant
      research on biocompatible gene carriers for therapeutic purposes. Varied
      biodegradable polymer-based architectures have been used to create new
      compositions with unique properties suitable for sustained gene delivery. This
      review presents the most recent advances in various polymeric systems: hydrogels,
      microspheres, nanospheres and scaffolds, having complex architectures to
      encapsulate and deliver functional genes. Through the recombination of different
      existing polymer systems, the multicomplex systems can be further endowed with
      new properties for better-targeted biomedical applications.

PMID- 28428057
TI  - Natural killer cells differentiated in vitro from cord blood CD34+ cells are more
      advantageous for use as an immunotherapy than peripheral blood and cord blood
      natural killer cells.
AB  - BACKGROUND AIMS: Natural killer (NK) cells have the potential to become a
      successful immunotherapy as they can target malignant cells without being direct
      effectors of graft-versus-host disease. Our group has previously shown that large
      numbers of functional NK cells can be differentiated in vitro from umbilical cord
      blood (CB) CD34+ cells. To produce a clinically relevant and effective
      immunotherapy, we hypothesized that it is essential that the NK cells are able to
      proliferate and persist in vivo while maintaining an optimal activation status
      and killing capacity. METHODS: We evaluated the proliferation capacity, telomere
      length and terminal differentiation markers expressed by NK cells differentiated
      in vitro. We also determined how their cytotoxicity compared with peripheral
      blood (PB) NK cells and CBNK cells when targeting patient acute myeloid leukemia
      (AML) blasts and solid tumor cell lines. RESULTS: We found that the
      differentiated NK cells could respond to interleukin-2 and proliferate in vitro.
      Telomere length was significantly increased, whereas CD57 expression was
      significantly reduced compared with PBNK cells. The cytotoxicity of the
      differentiated NK cells was equivalent to that of the PBNK and CBNK cell
      controls, and priming consistently led to higher levels of killing of patient
      leukemic blasts and solid tumor cell lines in vitro. Interestingly, this
      activation step was not required to observe killing of patient AML blasts in
      vivo. CONCLUSION: We are able to generate NK cells from CBCD34+ cells in high
      numbers, allowing for multiple infusions of highly cytotoxic NK cells that have
      potential to further proliferate in vivo, making them a desirable product for
      application as an immunotherapy in the clinic.

PMID- 28428058
TI  - The Pseudomonas aeruginosa lectin LecA triggers host cell signalling by
      glycosphingolipid-dependent phosphorylation of the adaptor protein CrkII.
AB  - The human pathogen Pseudomonas aeruginosa induces phosphorylation of the adaptor
      protein CrkII by activating the non-receptor tyrosine kinase Abl to promote its
      uptake into host cells. So far, specific factors of P. aeruginosa, which induce
      Abl/CrkII signalling, are entirely unknown. In this research, we employed human
      lung epithelial cells H1299, Chinese hamster ovary cells and P. aeruginosa wild
      type strain PAO1 to study the invasion process of P. aeruginosa into host cells
      by using microbiological, biochemical and cell biological approaches such as
      Western Blot, immunofluorescence microscopy and flow cytometry. Here, we
      demonstrate that the host glycosphingolipid globotriaosylceramide, also termed
      Gb3, represents a signalling receptor for the P. aeruginosa lectin LecA to induce
      CrkII phosphorylation at tyrosine 221. Alterations in Gb3 expression and LecA
      function correlate with CrkII phosphorylation. Interestingly, phosphorylation of
      CrkIIY221 occurs independently of Abl kinase. We further show that Src family
      kinases transduce the signal induced by LecA binding to Gb3, leading to CrkY221
      phosphorylation. In summary, we identified LecA as a bacterial factor, which
      utilizes a so far unrecognized mechanism for phospho-CrkIIY221 induction by
      binding to the host glycosphingolipid receptor Gb3. The LecA/Gb3 interaction
      highlights the potential of glycolipids to mediate signalling processes across
      the plasma membrane and should be further elucidated to gain deeper insights into
      this non-canonical mechanism of activating host cell processes.

PMID- 28428059
TI  - The decreased growth performance and impaired immune function and structural
      integrity by dietary iron deficiency or excess are associated with TOR, NF
      kappaB, p38MAPK, Nrf2 and MLCK signaling in head kidney, spleen and skin of grass
      carp (Ctenopharyngodon idella).
AB  - This study was conducted to investigate the effects of dietary iron on the
      growth, and immune function and structural integrity in head kidney, spleen and
      skin as well as the underlying signaling of young grass carp (Ctenopharyngodon
      idella). Total 630 grass carp (242.32 +/- 0.58 g) were fed diets containing
      graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37
      mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was
      added with ferrous sulfate) diet for 60 days. Then, a challenge test was
      conducted by infection of Aeromonas hydrophila for 14 days. The results firstly
      showed that compared with optimal iron level, iron deficiency decreased lysozyme
      (LZ) and acid phosphatase (ACP) activities, complement 3 (C3), C4 and
      immunoglobulin M (IgM) contents and down-regulated the mRNA levels of
      antibacterial peptides, anti-inflammatory cytokines, inhibitor of kappaBalpha
      (IkappaBalpha), target of rapamycin (TOR) and ribosomal protein S6 kinase 1
      (S6K1), whereas up-regulated the mRNA levels of pro-inflammatory cytokines,
      nuclear factor kappa B (NF-kappaB) p65, IkappaB kinases beta (IKKbeta) and eIF4E
      binding protein (4E-BP) in head kidney and spleen of young grass carp (P < 0.05),
      indicating that iron deficiency impaired immune function in head kidney and
      spleen of fish. Secondly, iron deficiency down-regulated the mRNA levels of B
      cell lymphoma-2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), and inhibitor of
      apoptosis protein (IAP), and decreased activities and mRNA levels of antioxidant
      enzymes, down-regulated the mRNA levels of NF-E2-related factor 2 (Nrf2) and
      tight junction complexes, and up-regulated mRNA levels of cysteinyl aspartic acid
      protease (caspase) -2, -3, -7, -8, -9, apoptotic protease activating factor-1
      (Apaf-1), Bcl-2 associated X protein (Bax), Fas ligand (FasL), p38 mitogen
      activated protein kinase (p38MAPK), Kelch-like ECH-associating protein (Keap) 1a,
      Keap1b, claudin-12 and myosin light chain kinase (MLCK), and increased
      malondialdehyde (MDA), protein carbonyl (PC) and reactive oxygen species (ROS)
      contents in head kidney and spleen of young grass carp (P < 0.05), indicating
      that iron deficiency impaired structural integrity in head kidney and spleen of
      fish. Thirdly, iron deficiency increased skin hemorrhage and lesion morbidity,
      and impaired immune function and structural integrity in skin of fish. Fourthly,
      iron excess decreased growth and impaired the immune function and structural
      integrity in head kidney, spleen and skin of fish. Besides, in young grass carp,
      based on PWG and ability against skin hemorrhage and lesion, the efficacy of
      ferrous fumarate relative to ferrous sulfate was 140.32% and 126.48%,
      respectively, and the iron requirements based on PWG, ability against skin
      hemorrhage and lesion, ACP activities and MDA contents in head kidney and spleen
      were estimated to be 75.65, 87.03, 79.74, 78.93, 83.17 and 82.14 mg/kg diet
      (based on ferrous fumarate), respectively.

PMID- 28428060
TI  - Effects of chronic ammonia exposure on ammonia metabolism and excretion in marine
      medaka Oryzias melastigma.
AB  - Ammonia is highly toxic to aquatic organisms, but whether ammonia excretion or
      ammonia metabolism to less toxic compounds is the major strategy for
      detoxification in marine fish against chronic ammonia exposure is unclear to
      date. In this study, we investigated the metabolism and excretion of ammonia in
      marine medaka Oryzias melastigma during chronic ammonia exposure. The fish were
      exposed to 0, 0.1, 0.3, 0.6, and 1.1 mmol l-1 NH4Cl spiked seawater for 8 weeks.
      Exposure of 0.3-1.1 mmol l-1 NH4Cl had deleterious effects on the fish, including
      significant reductions in growth, feed intake, and total protein content.
      However, the fish could take strategies to detoxify ammonia. The tissue ammonia
      (TAmm) in the 0.3-1.1 mmol l-1 NH4Cl treatments was significantly higher than
      those in the 0 and 0.1 mmol l-1 NH4Cl treatments after 2 weeks of exposure, but
      it recovered with prolonged exposure time, ultimately reaching the control level
      after 8 weeks. The amino acid catabolic rate decreased to reduce the gross
      ammonia production with the increasing ambient ammonia concentration. The
      concentrations of most metabolites remained constant in the 0-0.6 mmol l-1 NH4Cl
      treatments, whereas 5 amino acids and 3 energy metabolism-related metabolites
      decreased in the 1.1 mmol l-1 NH4Cl treatment. JAmm steadily increased in ambient
      ammonia from 0 to 0.6 mmol l-1 and slightly decreased when the ambient ammonia
      concentration increased to 1.1 mmol l-1. Overall, marine medaka cope with
      sublethal ammonia environment by regulating the tissue TAmm via reducing the
      ammonia production and increasing ammonia excretion.

PMID- 28428055
TI  - Sex differences in cardiovascular disease - Impact on care and outcomes.

PMID- 28428061
TI  - Identification and characterization of an interleukin-16-like gene from pacific
      white shrimp Litopenaeus vannamei.
AB  - Interleukins are a group of cytokines that play essential roles in immune
      regulation. Almost all interleukin genes are only found in vertebrates. In this
      study, an interleukin-16-like gene (LvIL-16L) was identified from Pacific white
      shrimp, Litopenaeus vannamei. LvIL-16L was predicted to encode a precursor (pro
      LvIL-16L) with 1378 amino acids, sharing similarities with predicted pro-IL-16
      like proteins from insects. The C-terminus of pro-LvIL-16L protein contained two
      PDZ domains homologous to the mature IL-16 cytokine of vertebrates. In tissues,
      LvIL-16L could be processed into a ~36 kDa mature peptide through a caspase-3
      cleavage site, which was verified by in vitro site mutation analysis and in vivo
      RNA interference (RNAi) experiments. The LvIL-16L mRNA could be detected in all
      the analyzed tissues and the expression of LvIL-16L was significantly up
      regulated after immune stimulation. Using RNAi strategy, the role of LvIL-16L in
      immune responses was initially investigated. Interestingly, knockdown of LvIL-16L
      could significantly increase the mortality of the Vibro parahaemolyticus infected
      shrimps but reduce that of the WSSV infected shrimps, suggesting that LvIL-16L
      could have opposite effects on the antiviral and antibacterial immune responses
      in shrimp. To our knowledge, this is the first study of an IL-16-like gene in
      invertebrates, which could help to elucidate interleukin evolution and regulatory
      mechanisms of shrimp immune responses.

PMID- 28428062
TI  - A nomogram to predict prognosis after surgery in early stage non-small cell lung
      cancer in elderly patients.
AB  - BACKGROUND: The aim of this study was to identify risk factors affecting overall
      survival (OS) of elderly patients with early stage NSCLC, and develop a nomogram
      for prognostic prediction of these patients using data from the Surveillance,
      Epidemiology, and End Results (SEER) database. METHODS: Data from the SEER
      database of patients aged >= 65 years with early (T1N0M0) NSCLC diagnosed between
      2004 and 2013 were examined. The prognostic effect of each variable on survival
      was evaluated using the Kaplan-Meier method and the Cox proportional hazards
      regression model. A nomogram was formulated to predict the 3- and 5-year OS rates
      of elderly patients with early stage NSCLC. RESULTS: Finally, a total of 20,782
      patients were included in this research. Cox regression analysis showed that sex,
      age, pathological type, diameter, differentiation, and surgery type were
      independent risk factors. A nomogram was formulated based on the results of
      multivariate analysis (all p < 0.001) and validated using an internal bootstrap
      resampling approach, which showed that the nomogram exhibited a sufficient level
      of discrimination according to the C-index (0.638, 95% CI = 0.629-0.647).
      CONCLUSIONS: The nomogram developed in this study demonstrated its discrimination
      capability to predict the 3- and 5-year OS rates of elderly patients with early
      stage NSCLC based on individual characteristics.

PMID- 28428063
TI  - Percutaneous endoscopical transforaminal approach versus PLF to treat the single
      level adjacent segment disease after PLF/PLIF: 1-2 years follow-up.
AB  - BACKGROUND: Adjacent segment disease (ASD) is a common complication after lumbar
      decompression and fusion surgery. Traditional revision-surgery, including
      posterior lumbar decompression and posterolateral fusion (PLF) or interbody
      fusion (PLIF) is traumatic. The percutaneous endoscopic transforaminal procedure
      (PE-TF) has been widely used in patients with lumbar disc disease. However, there
      are no reports about using PE-TF procedure to treat ASD in the current
      literature. OBJECTIVE: To compare the clinical outcomes between PE-TF and PLF for
      single-level ASD after PLF or PLIF. STUDY DESIGN: A retrospective study. SETTING:
      Department of Spine Surgery. METHODS: There were 64 patients diagnosed with
      single-level ASD and accepted revision surgery. 33 patients accepted PE-TF (Group
      A) and 31 underwent PLF (Group B). Oswestry Disability Index (ODI) and Japanese
      Orthopedic Association (JOA) scores were used to evaluate clinical outcomes.
      Complications, length of skin incision, hospitalization time and blood loss were
      investigated according to patient records. RESULTS: All symptoms had improved at
      the final follow-up. The improvement rate was 82.75% in group A and 86.28% in
      group B. The satisfactory clinical outcomes were similar in both groups with no
      recurrence in all cases. PE-TF procedure had significant advantages in the
      following items: traumatization, cosmetology, hospitalization time and blood
      loss. CONCLUSIONS: Clinical outcomes of using PE-TF procedure to treat single
      level ASD were similar to those of PLF approach, but PE-TF was less invasive and
      could shorten hospitalization time.

PMID- 28428064
TI  - Decreased transport time to the surgical intensive care unit.
AB  - INTRODUCTION: Extended stay in the emergency department (ED) is associated with
      worse outcomes in critically ill trauma patients. We conducted a human factors
      analysis to better understand impediments for patient flow when a surgical ICU
      (SICU bed is available in order to reduce ED LOS. METHODS: This is a
      retrospective review of all trauma patients admitted to a protected SICU through
      the ED during 2011 and 2014. In 2010, a 24-hour protected SICU bed protocol was
      implemented to make a bed readily available. During 2013 human factors analysis
      helped to describe flow disruptions; related interventions were introduced to
      facilitate rapid transport from the ED to SICU. The interventions required the
      following prior to CT scanning: immediate ICU bed orders placed by the ED
      physician and ED to ICU personnel communication. Direct transport from the CT
      scanner to the ICU was mandated. Data including patient demographics, injury
      severity, ED LOS, ICU LOS, and hospital LOS was collected and compared between
      2011 (PRE) and 2014 (POST). RESULTS: A total of 305 trauma patients admitted from
      the ED to the SICU were analyzed; 174 patients in 2011 (PRE) and 131 in 2014
      (POST). Average age was 46 years and patients had a mean admission GCS and injury
      severity score (ISS) of 12.3 and 15.9, respectively. The cohorts were similar in
      age, mechanism of injury, initial vital signs, and injury severity. After
      implementing the human factors interventions, decreases were noted in the mean ED
      LOS (2.4 v. 3.0 hours, p=0.005) and ICU LOS (4.0 v. 4.8 days, p=0.023). No
      differences in hospital LOS or mortality were observed. CONCLUSIONS: While an
      open SICU bed protocol may facilitate rapid transport of trauma patients from the
      ED to the ICU, additional human factors interventions emphasizing improved
      communication and coordination can further reduce time spent in the ED. LEVEL OF
      EVIDENCE: Level IV, Economic/Decision.

PMID- 28428065
TI  - In vivo studies investigating biodistribution of nanoparticle-encapsulated
      rhodamine B delivered via dissolving microneedles.
AB  - Nanoparticles (NPs) have undergone extensive investigation as drug delivery and
      targeting vehicles. NP delivery is often via the parenteral route, reliant on
      administration using hypodermic needles, which can be associated with patient
      compliance issues and safety concerns. In the recent past, the intradermal
      delivery of NPs, via novel dissolving microneedle (MN) arrays has garnered
      interest in the pharmaceutical community. However, published studies using this
      combinatorial approach have been limited, in that they have focussed on the use
      of in vitro and ex vivo models only. The current study was designed to answer the
      fundamental question of how such NPs are distributed in an in vivo murine model,
      following MN-mediated delivery. Rhodamine B (RhB) was employed as a model tracer
      dye to facilitate study of biodistribution. Following MN application, RhB was
      detected in the livers, kidneys, spleens and superficial parotid lymph nodes of
      the mice. Uptake into the lymphatics was of particular note, as it points towards
      the potential for utilisation of a minimally-invasive MN delivery strategy in
      controlled targeting of active drug substances and vaccines to the lymphatics.
      The use of such a delivery system could, following further development, have far
      reaching benefits in enhancement of immunomodulatory and anti-cancer therapies.
      As a consequence, further investigation of MN/NP combinatorial delivery
      strategies is warranted.

PMID- 28428066
TI  - Effects of gold nanoparticle-based vaccine size on lymph node delivery and
      cytotoxic T-lymphocyte responses.
AB  - Although it has been shown that the size of nanoparticle-based vaccines is a key
      determining factor for the induction of immune responses, few studies have
      provided detailed analyses of thresholds or critical sizes of nanoparticle
      vaccines. Here we report effects of the size of gold nanoparticle (GNP)-based
      vaccines on their efficiency of delivery to lymph nodes (LNs) and induction of
      CD8+ T-cell responses. We further propose a threshold size of GNPs for use as an
      effective vaccine. To examine the effects of GNP size, we synthesized GNPs with
      diameters of 7, 14 and 28nm, and then conjugated them with recombinant ovalbumin
      (OVA) as a model antigen. The resulting OVA-GNPs had hydrodynamic diameter (HD)
      of ~10, 22, and 33nm for 7, 14 and 28nm GNPs, respectively and exhibited a size
      dependent increase in cellular uptake by dendritic cells (DCs) and subsequent T
      cell cross-priming and activation. Upon injection into a mouse footpad, both 22-
      and 33-nm OVA-GNPs showed much higher delivery efficiency to draining LNs than
      did 10-nm OVA-GNPs. An ex vivo restimulation assay using OVA as an antigen
      revealed that frequencies of OVA-specific CD8+ T cells were higher in mice
      immunized with 22- and 33-nm OVA-GNPs than in those immunized with 10-nm OVA
      GNPs; moreover, these cells were shown to be poly-functional. In a tumor
      prevention study, 22-nm OVA-GNPs showed greater antitumor efficacy, and higher
      infiltration of CD8+ T-cells and greater tumor cell apoptosis and cell death than
      10-nm OVA-GNPs. Taken together, our results suggest that the size threshold for
      induction of potent cellular responses and T-cell poly-functionality by GNPs lies
      between 10nm and 22nm, and highlight the importance of nanoparticle size as a
      critical parameter in designing and developing nanoparticle-based vaccines.

PMID- 28428067
TI  - Targeting and synergistic action of an antifungal peptide in an antibiotic drug
      delivery system.
AB  - Amphotericin B (AmB) has been widely used against fungal infections throughout
      almost the entire body, including the skin, nails, oral cavity, respiratory
      tract, and urinary tract. However, the development of AmB-loaded nanoparticles
      demands a novel technique that reduces its toxicity and other associated
      problems. Here, we developed a pH-responsive and redox-sensitive polymer-based
      AmB-delivery carrier system. In particular, this system was functionalized by
      conjugation with the antifungal peptide histatin 5, which acts both as a
      targeting ligand and a synergistic antifungal molecule against Candida albicans,
      a major systemic fungal pathogen of humans. Our results in vitro and in vivo
      suggest that this drug-delivery system may serve as a novel tool to facilitate
      the use of antimicrobial peptides as targeting ligands to pathogenic microbes,
      which would open new avenues of investigation in the field of drug delivery.

PMID- 28428069
TI  - Assessment of non-derivatized beta-N-methylamino-l-alanine (BMAA) neurotoxin in
      free form in urine of patients with nonspecific neurological symptoms.
AB  - The beta-N-methylamino-l-alanine (BMAA) is a non-proteinogenic amino acid
      discussed to be produced by cyanobacteria forming harmful blooms. Since BMAA is
      suspected etiological agent in neurodegenerative diseases, there is a need to
      study and validate whether and in what concentrations can BMAA be present in
      human tissues. The aim of the present study was to validate analytical and
      extraction procedures for quantification of non-derivatized BMAA in the urine
      using liquid chromatography and commercial ELISA Kit. The study was focused on
      BMAA in different forms - dissolved, protein associated and total. The validated
      protocol included SPE followed by HILIC MS/MS for analyses of non-derivatized
      free form of BMAA with a limit of quantification 20 ng/mL. The methods for other
      BMAA forms (i.e. protein-associated and total) were also assessed but high matrix
      interferences did not allow their implementation. The method was used for
      analyses of free BMAA in 23 urine samples from healthy volunteers and psychiatric
      patients suffering from nonspecific neurological symptoms. Traces of BMAA were
      suspectedly detected in a single urine sample but they were not unequivocally
      proved according to all conservative analytical criteria. BMAA was also not
      confirmed in a repeatedly collected sample from the same person. The evaluated
      commercial BMAA ELISA Kit (Abraxis) was not suitable for determination of BMAA in
      extracted urine samples because of systematically highly false positive results.
      In agreement with recent findings, analyses of BMAA appear to methodologically
      challenging, and further research on BMAA in human tissues (or its precursors
      with potency to form BMAA under natural conditions or - eventually - during
      sample processing) is needed to clarify its potential ethiological role in
      neurodegenerative diseases.

PMID- 28428071
TI  - Development of novel in silico model for developmental toxicity assessment by
      using naive Bayes classifier method.
AB  - Toxicological testing associated with developmental toxicity endpoints are very
      expensive, time consuming and labor intensive. Thus, developing alternative
      approaches for developmental toxicity testing is an important and urgent task in
      the drug development filed. In this investigation, the naive Bayes classifier was
      applied to develop a novel prediction model for developmental toxicity. The
      established prediction model was evaluated by the internal 5-fold cross
      validation and external test set. The overall prediction results for the internal
      5-fold cross validation of the training set and external test set were 96.6% and
      82.8%, respectively. In addition, four simple descriptors and some representative
      substructures of developmental toxicants were identified. Thus, we hope the
      established in silico prediction model could be used as alternative method for
      toxicological assessment. And these obtained molecular information could afford a
      deeper understanding on the developmental toxicants, and provide guidance for
      medicinal chemists working in drug discovery and lead optimization.

PMID- 28428068
TI  - Comparative analysis of gene expression profiles for several migrating cell types
      identifies cell migration regulators.
AB  - Cell migration is an instrumental process that ensures cells are properly
      positioned to support the specification of distinct tissue types during
      development. To provide insight, we used fluorescence activated cell sorting
      (FACS) to isolate two migrating cell types from the Drosophila embryo: caudal
      visceral mesoderm (CVM) cells, precursors of longitudinal muscles of the gut, and
      hemocytes (HCs), the Drosophila equivalent of blood cells. ~350 genes were
      identified from each of the sorted samples using RNA-seq, and in situ
      hybridization was used to confirm expression within each cell type or,
      alternatively, within other interacting, co-sorted cell types. To start, the two
      gene expression profiling datasets were compared to identify cell migration
      regulators that are potentially generally-acting. 73 genes were present in both
      CVM cell and HC gene expression profiles, including the transcription factor zinc
      finger homeodomain-1 (zfh1). Comparisons with gene expression profiles of
      Drosophila border cells that migrate during oogenesis had a more limited overlap,
      with only the genes neyo (neo) and singed (sn) found to be expressed in border
      cells as well as CVM cells and HCs, respectively. Neo encodes a protein with Zona
      pellucida domain linked to cell polarity, while sn encodes an actin binding
      protein. Tissue specific RNAi expression coupled with live in vivo imaging was
      used to confirm cell-autonomous roles for zfh1 and neo in supporting CVM cell
      migration, whereas previous studies had demonstrated a role for Sn in supporting
      HC migration. In addition, comparisons were made to migrating cells from
      vertebrates. Seven genes were found expressed by chick neural crest cells, CVM
      cells, and HCs including extracellular matrix (ECM) proteins and proteases. In
      summary, we show that genes shared in common between CVM cells, HCs, and other
      migrating cell types can help identify regulators of cell migration. Our analyses
      show that neo in addition to zfh1 and sn studied previously impact cell
      migration. This study also suggests that modification of the extracellular milieu
      may be a fundamental requirement for cells that undergo cell streaming migratory
      behaviors.

PMID- 28428070
TI  - NO production and potassium channels activation induced by Crotalus durissus
      cascavella underlie mesenteric artery relaxation.
AB  - Animal toxins are natural resources for pharmacological studies. The venom of
      Crotalus durissus cascavella (C.d. cascavella) may be a source in the bio
      prospecting of new anti-hypertensive agents. The aim of this study was to
      investigate vascular effects of the venom of C.d. cascavella in normotensive
      rats. Studies were performed using isolated mesenteric artery segments and aortic
      endothelial cells. The cumulative administration of the venom of C.d. cascavella
      (0.001-30 MUg/mL) on phenylephrine (Phe; 10 MUM) pre-contracted rings induced a
      concentration-dependent vasorelaxation in the presence of vascular endothelium
      (Emax = 47.9 +/- 5.0% n = 8), and its effect was almost abolished in the absence
      of endothelium (Emax = 5.8+/- 2.4% n = 5 (***p < 0.001)). Tissue viability was
      maintained as there was no difference in the contractile capacity of rings before
      and after the administration of venom. The vasorelaxant effect of the venom was
      also abolished when arteries were pre-contracted with potassium chloride (KCl; 80
      mM) (Emax = 6.4+/- 0.9% n = 5, ***p < 0.001). When assessing the participation of
      endothelium-derived relaxing factors, it was noted that non-selective COX
      inhibition with indomethacin (10 MUM) caused a significant reduction in the
      vasorelaxant effect of C.d. cascavella (*p < 0.05). When investigating the
      participation of NO released by endothelium, there was a significant reduction of
      the vasorelaxant effect of venom in rings treated with L-NAME (100 MUM; Emax =
      17.5+/- 2.2% n = 6; **p < 0.01). Similar results were noted in the presence of
      ODQ (10 MUM), an inhibitor of soluble guanylyl cyclase (Emax = 11.2+/- 3.5%, n =
      6) and PTIO (100 MUM), a stable radical scavenger for nitric oxide (Emax =
      10.77+/- 3.6%, n = 6). Moreover, the venom induced the release of NO by isolated
      aortic endothelial cells through amperometric studies. When assessing the
      participation of K+ channels on the vasodilatory response of the venom, tyrode
      solution with 20 mM of KCl caused a significant reduction in the relaxation
      response (p < 0.001) (Emax = 21.3 +/- 8%, n = 7), as did inhibitor of delayed
      rectifier K+ channels (4-amynopiridine 1 mM; Emax = 9.5 +/- 1.3, %, n = 5, ***p <
      0.001), and vasorelaxation was almost abolished in the presence of Iberiotoxin
      (IbTx 100 nM). Therefore, these results suggest that the venom of C.d. cascavella
      induces vasorelaxation in superior mesenteric artery rings of normotensive rats
      in an endothelium-dependent manner. Specifically, the venom stimulates the
      generation of endothelium-derived relaxing factors, especially NO, and activates
      vascular smooth muscle hyperpolarization through K+ channels. These data
      illustrate that C.d. cascavella is a source of bioactive molecules and therefore
      has therapeutic potential in the treatment of cardiovascular diseases such as
      hypertension.

PMID- 28428072
TI  - Membrane lipid alterations in the metabolic syndrome and the role of dietary
      oils.
AB  - The metabolic syndrome is a cluster of pathological conditions, including
      hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels
      that is of great concern worldwide, as individuals with metabolic syndrome have
      an increased risk of type-2 diabetes and cardiovascular disease. Insulin
      resistance, the key feature of the metabolic syndrome, might be at the same time
      cause and consequence of impaired lipid composition in plasma membranes of
      insulin-sensitive tissues like liver, muscle and adipose tissue. Diet
      intervention has been proposed as a powerful tool to prevent the development of
      the metabolic syndrome, since healthy diets have been shown to have a protective
      role against the components of the metabolic syndrome. Particularly, dietary
      fatty acids are capable of modulating the deleterious effects of these
      conditions, among other mechanisms, by modifications of the lipid composition of
      the membranes in insulin-sensitive tissues. However, there is still scarce data
      based of high-level evidence on the effects of dietary oils on the effects of the
      metabolic syndrome and its components. This review summarizes the current
      knowledge on the effects of dietary oils on improving alterations of the
      components of the metabolic syndrome. It also examines their influence in the
      modulation of plasma membrane lipid composition and in the functionality of
      membrane proteins involved in insulin activity, like the insulin receptor, GLUT
      4, CD36/FAT and ABCA-1, and their effect in the metabolism of glucose, fatty
      acids and cholesterol, and, in turn, the key features of the metabolic syndrome.
      This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs
      Targeting Biomembranes edited by Pablo V. Escriba.

PMID- 28428073
TI  - Isosteviol prevents the prolongation of action potential in hypertrophied
      cardiomyoctyes by regulating transient outward potassium and L-type calcium
      channels.
AB  - Cardiac hypertrophy is a thickening of the heart muscle that is associated with
      cardiovascular diseases such as hypertension and myocardial infarction. It occurs
      initially as an adaptive process against increased workloads and often leads to
      sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is
      attributed to hypertrophy-induced destabilization of cardiac electrical activity,
      especially the prolongation of the action potential. The reduced activity of Ito
      is demonstrated to be responsible for the ionic mechanism of prolonged action
      potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of
      stevioside, plays a protective role in a variety of stress-induced cardiac
      diseases. Here we report effects of STV on rat ISO-induced hypertrophic
      cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by
      decreasing cell area of hypertrophied cardiomyocytes. STV application prevented
      the prolongation of action potential which was prominent in hypertrophied cells.
      The decrease and increase of current densities for Ito and ICaL observed in
      hypertrophied myocytes were both prevented by STV application. In addition, the
      results of qRT-PCR suggested that the changes of electrophysiological activity of
      Ito and ICaL are correlated to the alterations of the mRNA transcription level.

PMID- 28428074
TI  - Melittin inhibits tumor growth and decreases resistance to gemcitabine by
      downregulating cholesterol pathway gene CLU in pancreatic ductal adenocarcinoma.
AB  - Melittin is a Chinese traditional medicine for treating chronic inflammation,
      immunological diseases and cancers, however, the efficacy of melittin and its
      mechanism for treating pancreatic ductal adenocarcinoma (PDAC) are still unknown.
      Here we investigated the anti-cancer activity of melittin and its regulated
      mechanism(s) in the PDAC models. Melittin was found to suppress tumor growth by
      promoting cell apoptosis and cell-cycle arrest. Interestingly, the microarray
      analyses demonstrated that melittin significantly regulated cholesterol
      biosynthesis pathway during treatment. For instance, the cholesterol pathway gene
      clusterin (CLU) was highly downregulated by melittin which also enhanced
      gemcitabine sensitivity in PDAC cells by inhibiting CLU expression. In contrast,
      overexpression of CLU significantly diminished melittin mediated tumor
      suppression and gemcitabine sensitization, suggesting that CLU is the target of
      melittin. Furthermore, in the xenograft mouse model, the combination therapy of
      melittin and gemcitabine is more efficacious for inhibiting PDAC tumor growth
      than either single regimen. Taken together, our study has indicated that melittin
      is capable of suppressing tumor growth and promoting gemcitabine sensitivity in
      PDAC by downregulating cholesterol pathway.

PMID- 28428076
TI  - Myricetin suppresses invasion and promotes cell death in human placental
      choriocarcinoma cells through induction of oxidative stress.
AB  - Myricetin is a bioactive compound found in a variety of vegetables and fruits,
      and its anti-cancer effects are well known. In this study, we confirmed that
      myricetin reduced proliferation of two choriocarcinoma cell lines (JAR and JEG-3)
      and also promoted apoptosis and regulated cell cycle progression in a dose
      dependent manner in JAR and JEG-3 cells. In addition, we found that invasive and
      pro-angiogenic properties of malignant JAR and JEG-3 trophoblast cells were
      attenuated by myricetin treatment via MAPK and PI3K/AKT signaling pathways. In
      addition, we found that ROS production, lipid peroxidation, glutathione
      depletion, and loss of mitochondrial membrane potentials were enhanced in JAR and
      JEG-3 cells treated with myricetin. Moreover, myricetin augmented cytosolic Ca2+
      release from the endoplasmic reticulum associated with modulation of ER stress in
      JAR and JEG-3 cells. Our results also revealed that myricetin had synergistic
      antiproliferative effects with current chemotherapeutics, etoposide and
      cisplatin, on choriocarcinoma cells. Collectively, results of the present study
      provide strong evidence for the potential of myricetin to be an effective
      therapeutic for the prevention of human placental choriocarcinomas.

PMID- 28428077
TI  - Molecular bases of the crosstalk between bone and muscle.
AB  - Exercise is an evolutionary conserved survival function that nowadays has
      beneficial health effects. The increased metabolic activity of contracting
      skeletal muscle affects the biology of many organs involved in regulating muscle
      functions. The discovery of hormones and cytokines secreted by bone and skeletal
      muscle during exercise, has recently added experimental credence to the notion
      that a crosstalk exists between these organs. Bone through the hormone
      osteocalcin, promotes exercise capacity in the mouse. After binding to a G
      coupled protein receptor, Gprc6a, osteocalcin increases nutrients uptake and
      catabolism in myofibers during exercise. The catabolic aspect of osteocalcin
      distinguishes it from insulin signaling. In addition, osteocalcin regulates the
      endocrine function of skeletal muscle because it enhances the expression of
      interleukin-6 (IL-6). IL-6 is produced and secreted by contracting skeletal
      muscle and exerts autocrine, paracrine and systemic effects. One of the systemic
      functions of IL-6 is to drive the generation of bioactive osteocalcin.
      Altogether, these studies have revealed a feed-forward loop between bone and
      skeletal muscle that are necessary and sufficient for optimum exercise capacity.
      This endocrine regulation of exercise biology, suggest novel and adapted
      strategies for the prevention or treatment of age related muscle loss.

PMID- 28428075
TI  - Immunotherapy of hepatocellular carcinoma using chimeric antigen receptors and
      bispecific antibodies.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide with
      an overall survival rate of less than 15% in developed countries. Despite
      attempts at new therapeutic strategies, the majority of patients succumb to this
      cancer. Buttressed by the highly successful clinical impact in melanoma,
      immunotherapy is gaining momentum as the next treatment modality for many human
      cancers. Chimeric antigen receptors (CAR) contain the antigen binding moieties of
      a monoclonal antibody and the co-stimulatory and signaling domains associated
      with effector receptor signaling. Bispecific antibodies (BsAb) combine the
      binding specificities of two different monoclonal antibodies, one activating a
      receptor on a killer effector cell, while the other engaging a tumor-associated
      antigen to initiate tumor cytotoxicity. In this review, we survey the HCC targets
      for which CARs and bispecific antibodies have been generated. The pros and cons
      of these targets for T-cell and Natural Killer cell based immunotherapy will be
      discussed.

PMID- 28428078
TI  - Kinetic reconstruction reveals time-dependent effects of romosozumab on bone
      formation and osteoblast function in vertebral cancellous and cortical bone in
      cynomolgus monkeys.
AB  - Romosozumab, a humanized monoclonal sclerostin antibody under development for the
      treatment of osteoporosis, has a unique mechanism of action on bone-increasing
      bone formation and decreasing bone resorption. The effects on bone formation are
      transient, eliciting a rapid increase in bone formation that attenuates with
      continued treatment. Although bone formation attenuates, bone mineral density
      (BMD) continues to increase. To explore potential tissue-level mechanisms that
      could contribute to a progressive increase in spine BMD, we used kinetic
      reconstruction techniques to examine the effects of romosozumab on modeling and
      remodeling units in vertebral cancellous bone from adult cynomolgus monkeys
      administered romosozumab for 10 and 28weeks. The 10-week study duration captured
      a period of high modeling-based bone formation, and the 28-week study duration
      followed the self-regulation or attenuation of bone formation in cancellous bone
      that occurs with long-term treatment. Sequential fluorochrome labels applied for
      the kinetic reconstruction were also used to evaluate treatment effects on
      osteoblast function as early as 3weeks, and on bone formation and bone accrual in
      the vertebral cortex over 28weeks. Kinetic reconstruction of remodeling and
      modeling formation sites in vertebral cancellous bone revealed that romosozumab
      effected significant transient increases in mineral apposition rate in remodeling
      sites at week 3 that was not sustained with continued treatment. However,
      romosozumab treatment caused sustained improvement in fractional labeling of
      osteoid, an index of osteoblast efficiency, at remodeling formative sites at both
      weeks 10 and 28 that was the major contributor to significant increases in final
      wall thickness (W.Th) of remodeling packets. Remodeling W.Th matched the final
      W.Th of modeling packets at week 10. At both weeks 10 and 28, romosozumab
      significantly decreased eroded surface (ES/BS). At week 28, romosozumab also
      significantly reduced resorption period (Rs.P) and final resorption depth
      (Rs.De). The reduced final Rs.De combined with the increased W.Th resulted in a
      significant increase in bone balance (BB) at the level of the remodeling unit.
      Assessment of bone formation on the vertebral periosteal and endocortical
      surfaces following 28weeks of treatment revealed that romosozumab significantly
      increased bone formation on these surfaces, which had attenuated by week 28,
      resulting in significant increases in new periosteal and endocortical bone by
      week 28. These data suggest that multiple factors potentially contribute to the
      increase in spine BMD with romosozumab treatment. In the early period of
      treatment, increased modeling-based bone formation, increased W.Th at remodeling
      sites, a decrease in remodeling space secondary to decreased ES/BS in vertebral
      cancellous bone, and increased periosteal and endocortical bone formation in the
      vertebral cortex contribute to the early increase in spine BMD. Following the
      self-regulation of bone formation when modeling-based bone formation has
      attenuated, a decrease in remodeling space secondary to reduced ES/BS and a
      positive BB secondary to decreased final Rs.De and increased W.Th contribute to
      the progressive increase in spine BMD with long-term treatment.

PMID- 28428079
TI  - Mineralization-inhibiting effects of transglutaminase-crosslinked polymeric
      osteopontin.
AB  - Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N
      linked Glycoproteins) of mineral-binding matrix proteins found in bones and
      teeth. OPN is a well-known inhibitor of matrix mineralization, and enzymatic
      modification of OPN can affect this inhibitory function. In bone, OPN exists both
      as a monomer and as a high-molecular-weight polymer - the latter is formed by
      transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to
      create homotypic protein assemblies. OPN can be covalently crosslinked by
      transglutaminase 2 (TG2) and Factor XIII-A. Polymeric OPN has increased binding
      to collagen and promotes osteoblast adhesion, but despite these initial
      observations, its role in mineralization is not clear. In this study, we
      investigated the effect of polymerized OPN on mineralization using a
      hydroxyapatite crystal growth assay and mineralizing MC3T3-E1 osteoblast
      cultures. In the cultures, endogenous polymeric OPN was detected after
      mineralization occurred. In cell-free conditions, TG2 was used to crosslink
      bovine OPN into its polymeric form, and atomic force microscopy and dynamic light
      scattering revealed variably-sized, large branched aggregates ranging across
      hundreds of nanometers. These OPN polymers inhibited the growth of hydroxyapatite
      crystals in solution at concentrations similar to monomeric OPN, although the
      crosslinking slightly reduced its inhibitory potency. When added to MC3T3-E1
      osteoblast cultures, this exogenous polymeric OPN essentially did not inhibit
      mineralization when given during the later mineralization stages of culture;
      however, cultures treated early and then continuously with polymeric OPN
      throughout both the matrix assembly and mineral deposition stages showed reduced
      mineralization. Immunoblotting of protein extracts from these continuously
      treated cultures revealed exogenous OPN polymers incorporated into mature matrix
      that had not yet mineralized. These results suggest that in bone, the increased
      size and branched structure of crosslinked inhibitory polymeric OPN near the
      mineralization front could hinder it from accessing focal mineralization sites in
      the dense collagen-rich matrix, suggesting that OPN-crosslinking into polymers
      may represent a way to fine-tune the inhibitory potency of OPN on bone
      mineralization.

PMID- 28428080
TI  - The effect of preoperative lumbar epidural corticosteroid injection on
      postoperative infection rate in patients undergoing single-level lumbar
      decompression.
AB  - BACKGROUND CONTEXT: Lumbar epidural corticosteroid injections (LECIs) are
      frequently used in the treatment of lumbar intervertebral disc herniation with
      radiculopathy and lumbar spinal stenosis. Although widely used, their effect on
      the outcomes and complications of subsequent surgery is unclear. Postoperative
      infection can be a morbid complication following spine surgery, and recent
      literature has suggested that the risk may be increased in patients undergoing
      lumbar spinal surgery who had previously received LECIs. PURPOSE: The purpose of
      this study is to define the overall postoperative infection rate in patients
      undergoing lumbar spine decompression surgery in the Military Health System (MHS)
      patient population and examine the effects of LECIs on postoperative infection
      rates. STUDY DESIGN/SETTING: This is a retrospective case control database study
      (Level III study). PATIENT SAMPLE: The sample comprised all patients in the MHS
      who had a LECI before single-level lumbar decompression surgery from 2009 to
      2014. OUTCOME MEASURES: Postoperative infection within 90 days of surgery was
      used as the primary outcome measure for this study. Postoperative infection was
      identified using the International Classification of Diseases, 9th revision (ICD
      9) diagnosis codes for postoperative infection. METHODS: The Military Health
      System Data Repository (MDR) database was searched for all patients who underwent
      single-level lumbar spine decompression surgery from 2009 to 2014 using Current
      Procedural Terminology (CPT) codes. Current Procedural Terminology codes were
      used to identify the subset of patients who received preoperative LECIs. For
      patients receiving an injection, cohorts were established based on the timing of
      the preoperative injection: <30 days, 30-90 days, 91-180 days, 181-365 days, and
      >365 days. An age-based cohort, composed of patients 65 years of age and older,
      was also analyzed. A subgroup analysis of patients receiving more than one
      preoperative injection was performed. Postoperative infection within 90 days of
      surgery was identified using ICD-9 codes, and infection rates for all groups were
      calculated and compared with the control group who did not receive preoperative
      LECIs. No external funding was received for this study. RESULTS: We identified
      6,535 patients (847 preoperative LECI and 5,688 control) for analysis. The
      overall infection rate for patients undergoing single-level lumbar decompression
      surgery in the MHS was 0.81%. The rate ranged from 0% to 1.57% in the injection
      groups, with an overall infection rate in the injection group of 1.18% versus
      0.76% in the control group. Despite an increased odds ratio of 1.57 following
      injection, no statistically significant differences were found between the
      control group and any injection group based on timing of injection, patient age,
      or number of preoperative injections. CONCLUSIONS: The results of this study
      suggest that within the MHS, preoperative LECIs do not significantly increase the
      risk of postoperative infection after single-level lumbar decompression. If a
      difference does exist, it is likely small.

PMID- 28428081
TI  - Intraoperative image guidance compared with free-hand methods in adolescent
      idiopathic scoliosis posterior spinal surgery: a systematic review on screw
      related complications and breach rates.
AB  - BACKGROUND CONTEXT: Severe adolescent idiopathic scoliosis (AIS) is a three
      dimensional spinal deformity requiring surgery to stop curve progression.
      Posterior spinal instrumentation and fusion with pedicle screws is the standard
      surgery for AIS curve correction. Vascular and neurologic complications related
      to screw malpositioning are concerns in surgeries for AIS. Breach rates are
      reported at 15.7%, implant-related complications at 1.1%, and neurologic deficit
      at 0.8%. Free-hand screw insertion remains the prevailing method of screw
      placement, whereas image guidance has been suggested to improve placement
      accuracy. PURPOSE: This study aimed to systematically review the screw-related
      complication and breach rates from posterior spinal instrumentation and fusion
      with pedicle screws for patients with AIS when using free-hand methods for screw
      insertion compared with image guidance methods. STUDY DESIGN: This is a
      systematic review of prognosis, comparing image guidance with no image guidance
      in surgery. PATIENT SAMPLE: One randomized controlled trial and multiple
      prospective cohort studies that reported complication or breach rates in
      posterior spinal instrumentation and fusion with pedicle screws for AIS. OUTCOME
      MEASURES: Number of complications and breaches reported in databases or recorded
      from postoperative imaging. METHODS: Databases searched included MEDLINE, Embase,
      CINAHL, CENTRAL, and Web of Science. Studies of Level 3 evidence or greater as
      defined by the Centre for Evidence-Based Medicine were included. Articles were
      screened to focus on patients with AIS undergoing posterior fusion with pedicle
      screws or hybrid systems. Two independent reviewers screened abstracts, full
      texts, and extracted data. The Quality in Prognostic Studies (QUIPS) appraisal
      tool was used to determine studyrisk of bias (ROB). Level of evidence summary
      statements were formulated based on consistency and quality of reporting.
      RESULTS: Seventy-nine cohort studies were identified, including four comparing
      computed tomography (CT) guidance with free-hand methods head-to-head, eight on
      image guidance, and 671. on free-hand methods alone. Moderate evidence from
      individual head-to-head studies show CT guidance has lower breach rates than free
      hand methods. No complications were found in these studies. From individual
      cohort studies, moderate evidence shows CT guidance has lower point estimates of
      breach rates than free-hand methods at 7.9% compared with 9.7%-17.1%. Screw
      related complication rates are conflicting at 0% in CT navigation compared with
      0%-1.7% in 13 low- and moderate-quality studies. CONCLUSIONS: Although point
      estimates on breach rates are decreased with CT navigation compared with free
      hand methods, complication rates remain conflicting between the two methods.
      Current evidence is limited by small sample sizes, lack of comparison groups, and
      poorly predefined complications. Randomized controlled trials with larger samples
      with standardized definitions and recording of predefined breach and complication
      occurrences are recommended.

PMID- 28428082
TI  - Calcitonin receptor increases invasion of prostate cancer cells by recruiting
      zonula occludens-1 and promoting PKA-mediated TJ disassembly.
AB  - Almost all primary prostate cancers (PCs) and PC cell lines express calcitonin
      (CT) and/or its receptor (CTR), and their co-expression positively correlates
      with their invasiveness. Activation of the CT-CTR axis in non-invasive LNCaP
      cells induces an invasive phenotype. In contrast, silencing of CT/CTR expression
      in highly metastatic PC-3M cells markedly reduces their tumorigenicity and
      abolishes their ability to form distant metastases in nude mice. Our recent
      studies suggest that CTR interacts with zonula occludens 1 (ZO-1) through PDZ
      interaction to destabilize tight junctions and increase invasion of PC cells. Our
      results show that CTR activates AKAP2-anchored cAMP-dependent protein kinase A,
      which then phosphorylates tight junction proteins ZO-1 and claudin 3. Moreover,
      PKA-mediated phosphorylation of tight unction proteins required CTR-ZO-1
      interaction, suggesting that the interaction may bring CTR-activated PKA in close
      proximity of tight junction proteins. Furthermore, inhibition of PKA activity
      attenuated CT-induced loss of TJ functionality and invasion, suggesting that the
      phosphorylation of TJ proteins is responsible for TJ disassembly. Finally, we
      show that the prevention of CTR-ZO-1 interaction abolishes CT-induced invasion,
      and can serve as a novel therapeutic tool to treat aggressive prostate cancers.
      In brief, the present study identifies the significance of CTR-ZO-1 interaction
      in progression of prostate cancer to its metastatic form.

PMID- 28428084
TI  - Metabolomics of fescue toxicosis in grazing beef steers.
AB  - Fescue toxicosis (FT) results from consumption of tall fescue (Lolium
      arundinaceum) infected with an endophyte (Epichloe coenophiala) that produces
      ergot alkaloids (EA), which are considered key etiological agents of FT.
      Decreased weight gains, hormonal imbalance, circulating cholesterol disruption,
      and decreased volatile fatty acid absorption suggest toxic (E+) fescue-induced
      metabolic perturbations. Employing untargeted high-resolution metabolomics (HRM)
      to analyze E+ grazing-induced plasma and urine metabolome changes, fescue-naive
      Angus steers were placed on E+ or non-toxic (Max-Q) fescue pastures and plasma
      and urine were sampled before, 1, 2, 14, and 28 days after pasture assignment.
      Plasma and urine catecholamines and urinary EA concentrations were also measured.
      In E+ steers, urinary EA appeared early and peaked at 14 days. 13,090 urinary and
      20,908 plasma HRM features were detected; the most significant effects were
      observed earlier (2 days) in the urine and later (>=14 days) in the plasma.
      Alongside EA metabolite detection, tryptophan and lipid metabolism disruption
      were among the main consequences of E+ consumption. The E+ grazing-associated
      metabolic pathways and signatures described herein may accelerate development of
      novel early FT detection and treatment strategies.

PMID- 28428083
TI  - The roles of subcellularly located EGFR in autophagy.
AB  - The epidermal growth factor receptor (EGFR) is a well-studied receptor-tyrosine
      kinase that serves vital roles in regulation of organ development and cancer
      progression. EGFR not only exists on the plasma membrane, but also widely
      expressed in the nucleus, endosomes, and mitochondria. Most recently, several
      lines of evidences indicated that autophagy is regulated by EGFR in kinase-active
      and -independent manners. In this review, we summarized recent advances in our
      understanding of the functions of different subcellularly located EGFR on
      autophagy. Specifically, plasma membrane- and cytoplasm-located EGFR (pcEGFR)
      acts as a tyrosine kinase to regulate autophagy via the PI3K/AKT1/mTOR,
      RAS/MAPK1/3, and STAT3 signaling pathways. The kinase-independent function of
      pcEGFR inhibits autophagy by maintaining SLC5A1-regulated intracellular glucose
      level. Endosome-located EGFR phosphorylates and inhibits Beclin1 to suppress
      autophagy, while kinase-independent endosome-located EGFR releases Beclin1 from
      the Rubicon-Beclin1 complex to increase autophagy. Additionally, the nuclear EGFR
      activates PRKDC/PNPase/MYC signaling to inhibit autophagy. Although the role of
      mitochondria-located EGFR in autophagy is largely unexplored, the production of
      ATP and reactive oxygen species mediated by mitochondrial dynamics is most likely
      to influence autophagy.

PMID- 28428085
TI  - Galloylation of polyphenols alters their biological activity.
AB  - Polyphenols form one of the largest groups of natural compounds and possess a
      wide range of biological properties. These activities can be influenced by the
      galloyl moiety within their structures. A multitude of galloylated polyphenolic
      compounds occurs in nature, but galloylated phenols are also produced
      synthetically to influence their biological properties. This review provides a
      comprehensive summary of current knowledge about natural (galloylated catechins,
      theaflavins and proanthocyanidins, penta-O-galloyl-beta-d-glucose, gallotannins,
      ellagitannins, ellagic acid and flavonols) and semisynthetic gallates with a
      focus on their biological activity and toxicity issues. The effects of tea
      catechins (epicatechin, epigallocatechin, epicatechin gallate, and
      epigallocatechin gallate) and semisynthetic galloyl esters of the flavonolignans
      silybin and 2,3-dehydrosilybin from the milk thistle (Silybum marianum) on
      angiogenesis were used as examples of the structure-activity relationship (SAR)
      study.

PMID- 28428086
TI  - Evaluation of garlic oil in nano-emulsified form: Optimization and its efficacy
      in high-fat diet induced dyslipidemia in Wistar rats.
AB  - Garlic oil nanoemulsion was formulated using ultrasonic emulsification and the
      optimized garlic oil nanoemulsion ratio (1:2) of oil: surfactant showed
      spherical, with tiny droplet size 24.9 +/- 1.11 nm. It was observed that the
      prepared nanoemulsion has the zeta potential of -42.63 +/- 1.58 mV and a low
      polydispersity index of 0.2 +/- 0.09 with excellent stability. The formulation
      was subjected to in vivo acute and sub-acute toxicity. In acute toxicity study,
      single oral administration of 18.63 ml of garlic oil nanoemulsion/kg resulted in
      immediate mortality. However, garlic oil nanoemulsion (0.46 ml/kg) and tween 80
      (0.5 ml/kg) administered rats did not exhibit any toxicity and showed no changes
      in hematological and histological parameters. Further, both preventive and
      curative studies of garlic oil nanoemulsion were evaluated in high-fat diet fed
      dyslipidemic Wistar rats. Garlic oil nanoemulsion administered groups showed a
      significant effect in reducing the levels of lipid profiles (p < 0.001) compared
      to atorvastatin and garlic oil. Evaluation of lipid deposits in hepatic tissues
      was analyzed by Oil Red O staining, which revealed that garlic oil nanoemulsion
      administered rats markedly reduced the fat depots. Our findings suggest that
      garlic oil nano-emulsified form reduced toxicity and improved efficacy in
      preventing and treating dyslipidemia.

PMID- 28428087
TI  - Searching for new sources of innovative products for the food industry within
      halophyte aromatic plants: In vitro antioxidant activity and phenolic and mineral
      contents of infusions and decoctions of Crithmum maritimum L.
AB  - Aromatic halophyte plants are an outstanding source of bioactive compounds and
      natural products with potential use in the food industry. This work reports the
      in vitro antioxidant activity, toxicity, polyphenolic profile and mineral
      contents of infusions and decoctions from stems, leaves and flowers of Crithmum
      maritimum L., an aromatic and edible maritime halophyte (sea fennel). Aspalathus
      linearis (Burm.f.) Dahlg. (rooibos) herbal tea was used as a reference. Sea
      fennel's tisanes, particularly from leaves, were rich in phenolic compounds and
      five of them (p-hydroxybenzoic and ferulic acids, epicatechin, pyrocatechol and 4
      hydroxybenzaldehyde) were here described in C. maritimum for the first time.
      Chlorogenic acid was the dominant phenolic determined. Na was the most abundant
      mineral in all tisanes followed by Ca and Mg in leaves' tisanes and K in flowers.
      Sea fennel's samples had a similar antioxidant activity than those from A.
      linearis, and had no significant toxicity towards four different mammalian cell
      lines. Altogether, our results suggest that sea fennel can be a source of
      products and/or molecules for the food industry with antioxidant properties and
      minerals in the form, for example, of innovative health-promoting herbal
      beverages.

PMID- 28428088
TI  - Modulatory effect of curcumin against genotoxicity and oxidative stress induced
      by cisplatin and methotrexate in male mice.
AB  - The use of dietary antioxidants to modulate the toxic side effects induced by the
      anticancer drugs used in chemotherapy is currently eliciting considerable
      interest. This study was undertaken to investigate the possible protective role
      of the antioxidant curcumin (CMN) against genotoxicity, cytotoxicity and
      oxidative stress induced by cisplatin and methotrexate. Male mice were
      administered CMN orally in the dosages of 60, 90, and 120 mg/kg for three
      consecutive days before a single intraperitoneal injection of either cisplatin
      (6.5 mg/kg) or methotrexate (10 mg/kg). Animals were sacrificed 24 h after
      treatment with the used anticancer drugs. The protective role of CMN against the
      genotoxic and cytotoxic effects of the tested anticancer drugs was evaluated by
      using micronucleus and comet assay. The oxidative stress induced by the two
      anticancer drugs was assessed by determining malondialdehyde and reduced
      glutathione levels in kidney tissues. The results indicated that CMN pretreatment
      at the tested doses reduced the incidence of micronuclei and DNA damage induced
      by cisplatin and methotrexate. Moreover, malondialdhyde level was significantly
      decreased while glutathione level was significantly increased in CMN pretreated
      groups compared with cisplatin- and methotrexate-treated groups. This protective
      effect of CMN could be attributed to its ability to scavenge reactive oxygen
      species.

PMID- 28428089
TI  - Enhanced anti-rheumatic activity of methotrexate-entrapped ultradeformable
      liposomal gel in adjuvant-induced arthritis rat model.
AB  - The aim of this study is to investigate in vivo anti-rheumatic activity of
      methotrexate-entrapped ultradeformable liposomal gel (MTX-UDLs-gel) in adjuvant
      induced arthritis rat model. Methotrexate-entrapped ultradeformable liposomes
      (MTX-UDLs) with the optimal phosphatidylcholine to Tween 80 ratio (7:3, w/w) were
      incorporated into 1% Carbopol gel. MTX-UDLs-gel was characterized in terms of
      appearance, clarity, homogeneity, pH and drug content. The permeation of MTX-UDLs
      gel across rat skin was investigated using Franz diffusion cell. In vivo anti
      rheumatic activity of MTX-UDLs-gel was assessed in terms of edema volume, paw
      edema and leukocyte infiltration scores, histopathological analysis and
      inflammatory cytokines level in complete Freund's adjuvant (CFA)-induced
      arthritis rat model. MTX-UDLs-gel showed good homogeneity and clarity, neutral pH
      and about 99.5% drug content. The cumulative amount of MTX permeated for 24h from
      MTX-UDLs-gel (164.6MUg) was 1.5 and 2.15 times higher than that of MTX-CLs-gel
      (113.3MUg) and MTX-plain-gel (76.6MUg), respectively. MTX-UDLs-gel significantly
      alleviated the severity of inflammation by reducing edema volume, histological
      scores and accumulation of neutrophils and improving tissue architecture in CFA
      induced arthritis rat model. MTX-UDLs-gel effectively suppressed the expression
      of pro-inflammatory cytokines, TNF-alpha and IL-1beta, in paw tissues. In
      conclusion, the developed MTX-UDLs-gel has a great potential for effective
      delivery of MTX into the inflamed joints in rheumatoid arthritis.

PMID- 28428090
TI  - Preparation and characterization of lipid nanoparticle/pDNA complexes for STAT3
      downregulation and overcoming chemotherapy resistance in lung cancer cells.
AB  - Developments in the field of molecular oncology have revealed that resistance to
      chemotherapeutics is acqured through several mechanisms including overexpression
      of common oncogenic proteins. Signal Transducer and Activator of Transcription 3
      (STAT3) is one of these oncogenes that is overexpressed in many cancer types. RNA
      interference (RNAi) is proven powerful tool for downregulating STAT3, allowing re
      sensitization of resistant cancer cells. However, delivery of RNA interference
      mediating molecules for STAT3 downregulation in lung cancer cells is limited to a
      small number of studies most of which employ commercially available transfection
      kits. The aim of this study was to develop and evaluate cationic solid lipid
      nanoparticles for delivery of RNAi-mediating plasmid DNA in order to down
      regulate STAT3 in cisplatin resistant lung cancer cells. We focused on obtaining
      cSLN:plasmid DNA complexes with size below or equal to 100nm, and a positive zeta
      potential. Two successful candidate cSLN:plasmid DNA complexes (K2 and K3) were
      selected for in vitro tests and cell culture studies. These formulations have
      particle sizes of 98 and 93nm, and zeta potential values of 10.5 and 8.9mV,
      respectively. Plasmid DNA in these complexes was protected against DNaseI and
      serum-mediated degradation. Substantial part of DNA retained its supercoiled and
      circular conformation. TEM images showed nearly spherical complex structure. Both
      formulations reduced STAT3 expression by approx. 5-fold in cisplatin resistant
      Calu1 cell line and increased the sensitivity of cells to cisplatin.

PMID- 28428091
TI  - Characterization of the Effects of L-4-Chlorokynurenine on Nociception in
      Rodents.
AB  - : Upon systemic administration in rats, the prodrug L-4-chlorokynurenine (4-Cl
      KYN; AV-101; VistaGen Therapeutics, Inc, South San Francisco, CA) is rapidly
      absorbed, actively transported across the blood-brain barrier, and converted in
      astrocytes to 7-chlorokynurenic acid (7-Cl-KYNA), a potent and specific
      antagonist of the glycine B coagonist site of the N-methyl-D-aspartate (NMDA)
      receptor. We examined the effects of 4-Cl-KYN in several rat models of
      hyperalgesia and allodynia and determined the concentrations of 4-Cl-KYN and
      newly produced 7-Cl-KYNA in serum, brain, and spinal cord. Adult male rats were
      given 4-Cl-KYN (56, 167, 500 mg/kg), the NMDA receptor antagonist MK-801 (.1, .3,
      1.0 mg/kg), or gabapentin (33, 100, 300 mg/kg) intraperitoneally, and were then
      examined on rotarod, intraplantar formalin-evoked flinching, thermal escape in
      the normal and carrageenan-inflamed paw, and allodynia after sciatic nerve
      ligation. Our conclusions show that after systemic delivery, the highest 2 doses
      (167 and 500 mg/kg) of 4-Cl-KYN yielded brain concentrations of 7-Cl-KYNA
      exceeding its half maximal inhibitory concentration (IC50) at the glycine B site
      and resulted in dose-dependent antihyperalgesia in the 4 models of facilitated
      processing associated with tissue inflammation and nerve injury. On the basis of
      the relative dose requirements for analgesic actions and side effect profiles
      from these experiments, 4-Cl-KYN is predicted to have antihyperalgesic efficacy
      and a therapeutic ratio equal to gabapentin and superior to MK-801. PERSPECTIVE:
      These studies show that systemic administration of the prodrug 4-Cl-KYN produces
      high central nervous system levels of 7-Cl-KYNA, a potent and highly selective
      antagonist of the NMDA receptor. Compared with other drugs tested, 4-Cl-KYN has
      robust antinociceptive effects with a better side effect profile, highlighting
      its potential for treating hyperpathic pain states.

PMID- 28428092
TI  - Validation of the Pain Resilience Scale in a Chronic Pain Sample.
AB  - : Psychosocial factors that protect against negative outcomes for individuals
      with chronic pain have received increased attention in recent years. Pain
      resilience, or the ability to maintain behavioral engagement and regulate
      emotions as well as cognitions despite prolonged or intense pain, is one such
      factor. A measure of pain-specific resilience, the Pain Resilience Scale, was
      previously identified as a better predictor of acute pain tolerance than general
      resilience. The present study sought to validate this measure in a chronic pain
      sample, while also furthering understanding of the role of pain resilience
      compared with other protective factors. Participants with chronic pain completed
      online questionnaires to assess factors related to positive pain outcomes, pain
      vulnerability, pain intensity, and quality of life. A confirmatory factor
      analysis confirmed the 2-factor structure of the Pain Resilience Scale previously
      observed among respondents without chronic pain, although one item from each
      subscale was dropped in the final version. For this chronic pain sample,
      structural equation modeling showed that pain resilience contributes unique
      variance to a model including pain acceptance and pain self-efficacy in
      predicting quality of life and pain intensity. Further, pain resilience was a
      better fit in this model than general resilience, strengthening the argument for
      assessing pain resilience over general resilience. PERSPECTIVE: A modified
      version of the Pain Resilience Scale retained the original factor structure when
      tested in a chronic pain sample. Construct validity was supported by expected
      relationships with pain-related protective and vulnerability measures. Further, a
      model including positive pain constructs showed that pain resilience accounts for
      unique variability when predicting quality of life and pain intensity.

PMID- 28428093
TI  - Migraine Prevention Using Different Frequencies of Transcutaneous Occipital Nerve
      Stimulation: A Randomized Controlled Trial.
AB  - : This study's objective was to evaluate the efficacy and tolerability of
      transcutaneous occipital nerve stimulation (tONS) in patients with migraine, and
      to explore whether different tONS frequencies influenced treatment effectiveness.
      This was a randomized, controlled trial of tONS for prevention of migraine.
      Patients were randomized to 1 of 5 therapeutic groups before treatment for 1
      month. Groups A through C received tONS at different frequencies (2 Hz, 100 Hz,
      and 2/100 Hz), group D underwent sham tONS intervention, and group E received
      topiramate orally. The primary outcomes were the 50% responder rate and headache
      characteristics. A total of 110 patients completed the study. The 50% responder
      rate was significantly greater in the groups undergoing active tONS and
      topiramate, compared with sham-treated group. A significant reduction in headache
      intensity was noted in each test group compared with the sham group; the groups
      undergoing tONS at different frequencies did not differ significantly. From
      baseline to the 1-month treatment period, the tONS group with 100 Hz and
      topiramate group exhibited significant decreases in headache duration. We
      conclude that tONS therapy is a new promising approach for migraine prevention.
      It has infrequent and mild adverse events and may be effective among patients who
      prefer nonpharmacological treatment. PERSPECTIVE: This article introduces a
      randomized, controlled trial to illustrate tONS as a new approach for prevention
      of migraine. It shows tONS is well tolerated and could be considered as a
      promising treatment for patients who prefer to nonpharmacological therapy.

PMID- 28428095
TI  - Sjogren's syndrome: Clinical aspects.
AB  - Sjogren's syndrome (SS) is the 2nd most common chronic autoimmune rheumatic
      disease and associated with a high burden of illness. Morbidity arises not only
      from untreated xerostomia and keratoconjunctivitis sicca but also from extra
      glandular manifestations including the development of non-Hodgkin's B cell
      lymphomas. Proper diagnosis of SS requires objective evidence of dry eyes and/or
      objective evidence of dry mouth as well as proof of autoimmunity. The recent
      development of new international classification criteria and clinical practice
      guidelines for SS should not only enhance the existing standards of care but also
      facilitate further studies to improve future diagnosis and outcomes.

PMID- 28428094
TI  - CXCR6 gene characterization in two ethnically distinct South African populations
      and association with viraemic disease control in HIV-1-infected black South
      African individuals.
AB  - CXCR6 genetic variation was described for HIV-1-uninfected black (n=41) and
      Caucasian (n=40) South Africans. We also investigated the CXCR6 rs2234358 and
      rs2234355 single nucleotide polymorphisms in HIV-1 disease control in 124 HIV-1
      infected drug-naive black individuals [elite controllers (n=11), viraemic
      controllers (VCs, n=30), high viral load long-term nonprogressors (HVL LTNPs,
      n=11) and progressors (n=72)] compared to healthy controls (HCs; n=232). The
      rs2234358-T allele was underrepresented in VCs (40.0%) compared to HCs (59%,
      P=0.006), HVL LTNPs (72.7%, P=0.012) and progressors (59%, P=0.014). The
      rs2234358-TT genotype was underrepresented in VCs (7%) compared to progressors
      (32%; OR=6.57, P=0.006) and HCs (35%; OR=7.18, P=0.001, Pbonferroni=0.034). The
      rs2234355-GA genotype was overrepresented in VCs (80%) compared to HCs (50.4%;
      OR=0.25, P=0.003) and progressors (29.17%; OR=0.10, P=3.8*10-5,
      Pbonferroni=0.001). The combination of rs2234355-GA in the absence of rs2234358
      TT was overrepresented in VCs (80%) compared to HCs (32.6%, OR=0.12, P=1*10-6,
      Pbonferroni=3.4*10-5) and to progressors (16.7%; OR=0.05, P<1*10-8,
      Pbonferroni<1*10-7).

PMID- 28428096
TI  - Developing the PedsValue Modules-A National Pediatric High Value Care Curriculum.

PMID- 28428097
TI  - Care Coordination and Comprehensive Electronic Health Records are Associated With
      Increased Transition Planning Activities.
AB  - OBJECTIVE: Youth with special health care needs (YSHCN) require assistance from
      their pediatricians to transition to adult care. There are few data on what
      transition resources pediatricians have. In this article we discuss whether care
      coordination and/or comprehensive electronic health record (CEHR) implementation
      are associated with improved transition processes. METHODS: Using the American
      Academy of Pediatrics Periodic Survey #79, we report whether practices generated
      written transition plans, assisted in finding adult providers, and discussed
      confidentiality issues. Descriptive statistics and a logistic regression model
      were done to evaluate whether CEHR, care coordination, or practice and physician
      characteristics were associated with improved transition planning. RESULTS:
      Transition planning support in practices is low. Pediatricians with any care
      coordinator report more written transition plans for YSHCN (23% vs 6%; P < .001),
      assistance identifying adult providers (59% vs 39%; P < .001), and discussing
      confidentiality issues (50% vs 33%; P < .001). Pediatricians with a CEHR compared
      with those without are more likely to report written transition plans for YSHCN
      (24% vs 12%; P < .05) and discussing confidentiality issues (51% vs 39%; P <
      .05). In the logistic regression model, having care coordination (adjusted odds
      ratio, 11.1; 95% confidence interval, 5.9-21.3) and CEHR (adjusted odds ratio,
      2.6; 95% confidence interval, 1.5-5.0) were independently associated with higher
      odds of having a written transition plan. CONCLUSIONS: Only 1 in 5 pediatricians
      have a transition coordinator in their practice and just 15% have a CEHR, even as
      these resources are associated with improved transition processes for YSHCN.
      Policy decisions should be made to help practices with supports, such as care
      coordination and electronic health record implementation, to improve transitions
      to adulthood.

PMID- 28428098
TI  - Breast Cancer Risk Assessment and Screening in Transgender Patients.

PMID- 28428099
TI  - Nipple-Sparing Mastectomy and Its Application on BRCA Gene Mutation Carrier.
AB  - In breast cancer 1 (BRCA) gene mutation carriers, mastectomy is still the
      mainstay of treatment for breast cancers due to the increased risk of local
      recurrence. It is performed as a therapeutic, as well as prophylactic procedure.
      However, mastectomy with removal of nipple areolar complex (NAC) is associated
      with adverse cosmetic outcome. NAC sparing mastectomy (NSM), which results in
      better cosmetic outcome, has been performed in non-BRCA mutation carriers. While
      studies have shown that NSM is a oncologically safe in sporadic breast cancers,
      its application in BRCA mutation carriers is still controversial. Here we review
      the existing evidence of NSM and its application in BRCA mutation carriers.

PMID- 28428100
TI  - An overview of the safety pharmacology career of Dr. C.R. Hassler.
AB  - Each year the Safety Pharmacology Society (SPS) recognizes an investigator who
      has had a marked impact upon the discipline. The 2016 recipient of the SPS
      Distinguished Service Award (DSA) was Dr. Craig R. Hassler. Dr. Hassler is one of
      the founding members of the SPS and has been actively engaged in physiological
      research for over 46years. Dr. Hassler delivered a talk entitled "My 43Years at
      Battelle Memorial Institute" to meeting attendees. In this article an overview is
      provided of the illustrious career of Dr. Hassler along with an account of the
      numerous animal models that were developed at Battelle under his guidance over
      the years.

PMID- 28428101
TI  - All Wired Up: Migration of Endovascular Coils to the Common Bile Duct.

PMID- 28428102
TI  - Metastatic Breast Cancer Presenting as Esophageal Stricture.

PMID- 28428103
TI  - Characteristics and clinical implications of reactive germinal centers in the
      bone marrow.
AB  - Reactive germinal centers (GCs) in the bone marrow (BM) have been described in
      patients with autoimmune disorders, infections, malignancies, and following
      certain drug therapies, or as an isolated finding without obvious underlying
      disease. In this study, we describe the clinical conditions in which reactive GCs
      occur in BM samples, and their topography and accompanying laboratory and
      ancillary findings in the setting of a cancer center. We identified 32 BM
      specimens with reactive GCs with an estimated frequency less than 0.02% over a 12
      year period. Fifteen (46.9%) BM specimens had concurrent hematolymphoid
      neoplasms: most often a variety of small B-cell lymphomas, but also
      myelodysplastic syndromes. One (3.1%) case was involved by metastatic melanoma.
      Isolated reactive GCs were observed in 16 (50%) patients. Most BM specimens (n =
      25; 78.1%) showed only one reactive GC with a size ranging from 20 to 500 MUm,
      and most GCs (29/32) were nonparatrabecular. GCs were positive for CD10 and BCL6,
      and were negative for BCL2. CD3 and CD5 demonstrated T cells surrounding the GC
      and CD21, and CD23 highlighted follicular dendritic cells. Reactive GCs are
      uncommon and can be seen in association with hematolymphoid and other types of
      neoplasms or as an isolated finding. Reactive GCs are usually located in a
      nonparatrabecular distribution. A panel of immunohistochemical stains is useful
      to confirm the nonneoplastic nature of these GCs to avoid misdiagnosis as
      lymphoma or as histologic evidence of transformation in a patient with small B
      cell lymphoma in the bone marrow.

PMID- 28428104
TI  - Tumor budding in intestinal-type gastric adenocarcinoma is associated with nodal
      metastasis and recurrence.
AB  - Gastric adenocarcinoma (GAC) is a common cause of cancer-related death worldwide.
      GAC can be classified as intestinal or diffuse. Intestinal-type cancers are
      common and reported to have a better prognosis compared to diffuse cancers.
      Studies have shown the presence and amount of tumor budding in intestinal
      carcinomas of the colon and esophagus to predict nodal metastasis and recurrence.
      Our aim is to determine if tumor budding in intestinal-type GAC correlates with
      prognostic features. One hundred four patients treated with primary surgical
      excision between 1999 and 2013 were identified. Histologic type (intestinal,
      diffuse, or mixed), tumor grade, T-stage, and lymph node status were evaluated.
      Tumor bud scores were assigned to all intestinal-type cancers using methods
      previously described for colorectal adenocarcinoma. Scores of <1 were designated
      as low and >=1 as high. Tumor characteristics were as follows: 52 intestinal
      (50%), 36 diffuse (35%), and 16 mixed (15%). Of the 52 cases with intestinal
      histology, 4 were well (8%), 28 were moderately (54%), and 20 were poorly
      differentiated (38%). Thirty-three (63%) of the intestinal tumors had high tumor
      bud scores. Cases with high scores were associated with higher T-stage, N-stage,
      and grade (P<.001, P<.001, and P=.002). These also had a higher likelihood of
      recurrence (P=.007). In our cohort, high tumor bud scores in intestinal-type GAC
      have higher T-stage, N-stage, grade, and likelihood of recurrence. Assessment of
      tumor budding may guide clinical management in a subset of patients.

PMID- 28428105
TI  - Microcarcinoid arising in patients with long-standing ulcerative colitis:
      histological analysis.
AB  - Some case reports of neuroendocrine tumors and neuroendocrine carcinoma
      associated with ulcerative colitis (UC) have been published. Most neuroendocrine
      tumor cases are small lesions corresponding to microcarcinoids (MCs). However,
      published case reports have presented findings of MCs as single-case reports.
      Thus, the frequency of MCs is still unclear. In this study, we described the
      clinical and morphological features of 14 cases of UC-associated MCs and
      estimated the frequency of MCs. Consecutive patients with UC who underwent
      complete removal of the large intestine were assessed, and 135 patients were
      selected. Of the 135 cases, 14 cases (10.4%) in which MC lesions were observed
      histologically were classified as the MC group, and the remaining 121 cases were
      classified as the control group. Seven cases in the MC group (50%) exhibited
      colitic cancer. No cases in either group had distinct carcinoid tumors. All MC
      lesions were located in the rectum, and the sizes ranged from 0.1 to 5.5 mm.
      Eight cases (57%) had multiple MC lesions. The frequency of MCs in UC was
      estimated to be 10.4%. Most cases of MC were quite unlikely to develop into
      clinically distinct carcinoid tumors. Thus, when MC lesions remain microscopic,
      they may not represent true neoplasms, which require immediate surgical
      resection. Because MC often arose in cases with UC complicated by dysplasia or
      cancer, patients with UC whose rectal biopsies reveal MC may be at high risk of
      colitic cancer.

PMID- 28428106
TI  - GATA3 immunohistochemistry in urothelial carcinoma of the upper urinary tract as
      a urothelial marker and a prognosticator.
AB  - Immunohistochemistry of a transcription factor, GATA3, has been widely used as a
      promising urothelial marker in diagnostic surgical pathology practice. However,
      the expression status of GATA3 in upper urinary tract urothelial carcinomas
      (UUTUCs) and its prognostic significance have not been fully investigated. We
      immunohistochemically stained for GATA3 in 99 UUTUC samples and paired
      nonneoplastic urothelial tissues. GATA3 was positive in 51 (51.5%; 32 [32.3%]
      weak, 11 [11.1%] moderate, 8 [8.1%] strong) of 99 UUTUCs, which was significantly
      lower than in benign urothelium (79 [96.3%] of 82; 33 [40.2%] weak, 35 [42.7%]
      moderate, 11 [13.4%] strong; P<.001). However, there were no statistically
      significant associations between GATA3 expression and tumor grade, pT stage,
      lymph node involvement, or distant metastasis. Meanwhile, the rate of GATA3
      positivity was significantly higher (P=.004) in ureteral tumors (66.0%) than in
      renal pelvic tumors (35.6%). Kaplan-Meier and log-rank tests revealed that GATA3
      negativity was significantly associated with lower recurrence-free survival
      (P=.037 for all cases, P=.026 for muscle-invasive tumors) and cancer-specific
      survival (P=.007 for all cases, P=.012 for muscle-invasive tumors, P=.035 for
      cases with adjuvant chemotherapy) rates. Multivariate analysis further identified
      strong correlations of GATA3 expression with tumor progression (all cases: hazard
      ratio [HR], 0.479 [95% confidence interval {CI},0.229-1.003; P=.051]; muscle
      invasive tumors: HR, 0.387 [95% CI, 0.166-0.903; P=.028) or cancer-specific
      mortality (all cases: HR, 0.354 [95% CI, 0.135-0.925; P=.034]; muscle-invasive
      tumors: HR, 0.402 [95% CI, 0.149-1.086; P=.072]). Thus, compared with
      nonneoplastic urothelium, a significant decrease in the expression of GATA3 in
      UUTUC was seen. Moreover, loss of GATA3 expression was found to be an independent
      predictor of poor patient outcomes. Of note was that only roughly half of high
      grade and/or muscle-invasive UUTUCs were immunoreactive for GATA3.

PMID- 28428107
TI  - Clinicopathological factors associated with survival in patients with breast
      cancer brain metastasis.
AB  - Brain metastasis from breast cancer generally represents a catastrophic event yet
      demonstrates substantial biological heterogeneity. There have been limited
      studies solely focusing on the prognosis of patients with such metastasis. In
      this study, we carried out a comprehensive analysis in 108 consecutive patients
      with breast cancer brain metastases between 1997 and 2012 to further define
      clinicopathological factors associated with early onset of brain metastasis and
      survival outcomes after development of them. We found that lobular carcinoma,
      higher clinical stages at diagnosis, and lack of coexisting bone metastasis were
      significantly associated with a worse brain relapse-free survival when compared
      with brain-only metastasis. High histologic grade, triple-negative breast cancer,
      and absence of visceral involvement were unfavorable prognostic factors after
      brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and
      lack of coexisting bone involvement indicated a worse overall survival. Thus, the
      previously established prognostic factors in early stage or advanced breast
      cancers may not entirely apply to patients with brain metastases. Furthermore,
      the prognostic significance of the clinicopathological factors differed before
      and after a patient develops brain metastasis. This knowledge might help in
      establishing an algorithm to further stratify patients with breast cancer into
      prognostically significant categories for optimal prevention, screening, and
      treatment of their brain metastasis.

PMID- 28428108
TI  - The gene copy number of c-MET has a significant impact on progression-free
      survival in Korean patients with ovarian carcinoma.
AB  - The aim of this study was to compare the protein overexpression and gene copy
      number (GCN) of c-MET in ovarian carcinoma and to assess their prognostic roles
      in Korean women. MET protein expression and GCN status were determined using
      immunohistochemistry (IHC) and silver in situ hybridization, respectively, in 105
      ovarian carcinomas comprising 63 serous, 12 mucinous, 20 clear cell, and 10
      endometrioid carcinomas. All cases had been treated and followed up at a single
      institute in Seoul, Korea. MET protein overexpression was observed in 35 of 105
      (33.3%) ovarian carcinomas, with IHC 2+ in 27 and IHC 3+ in 8. The overexpression
      rates of serous, mucinous, clear cell, and endometrioid carcinomas were 14.3%,
      83.3%, 65.0%, and 30.0%, respectively. MET protein overexpression was significant
      in mucinous carcinoma (P < .001) and was correlated with better progression-free
      survival (PFS) (P = .028). High polysomy (HP) of chromosome 7 and gene
      amplification (GA) were found in 10 (9.5%) and 2 (1.9%) of the 105 ovarian
      carcinomas, respectively. Eleven of 12 cases were high-grade serous carcinomas.
      The remaining case was clear cell carcinoma. HP and GA were associated with a
      poor PFS (P = .001). There was no significant correlation between a high level of
      protein expression and increased GCN of MET (r = -0.127, P = .197). In Korean
      women, HP and GA of MET were significantly correlated with a poor PFS. MET GCN
      may serve as a biomarker for poor prognosis in patients with ovarian carcinoma.

PMID- 28428109
TI  - Why does acute primary angle closure happen? Potential risk factors for acute
      primary angle closure.
AB  - Acute primary angle closure is an ocular emergency and requires immediate
      management to avoid blindness. Narrow anterior chamber angle, advanced age,
      female gender, and Asian ethnic background are considered risk factors for acute
      primary angle closure. The predictive power of these factors is, however,
      relatively poor, and many questions remain unanswered because acute primary angle
      closure eventually develops in only a relatively small proportion of anatomically
      predisposed eyes. We summarize the potential roles of various factors in the
      pathogenesis of acute primary angle closure.

PMID- 28428110
TI  - Does Peak Urine Flow Rate Predict the Development of Incident Lower Urinary Tract
      Symptoms in Men with Mild to No Current Symptoms? Results from REDUCE.
AB  - PURPOSE: We determined whether decreased peak urine flow is associated with
      future incident lower urinary tract symptoms in men with mild to no lower urinary
      tract symptoms. MATERIALS AND METHODS: Our population consisted of 3,140 men from
      the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial with mild
      to no lower urinary tract symptoms, defined as I-PSS (International Prostate
      Symptom Score) less than 8. REDUCE was a randomized trial of dutasteride vs
      placebo for prostate cancer prevention in men with elevated prostate specific
      antigen and negative biopsy. I-PSS measures were obtained every 6 months
      throughout the 4-year study. The association between peak urine flow rate and
      progression to incident lower urinary tract symptoms, defined as the first of
      medical treatment, surgery or sustained and clinically significant lower urinary
      tract symptoms, was tested by multivariable Cox models, adjusting for various
      baseline characteristics and treatment arm. RESULTS: On multivariable analysis as
      a continuous variable, decreased peak urine flow rate was significantly
      associated with an increased risk of incident lower urinary tract symptoms (p =
      0.002). Results were similar in the dutasteride and placebo arms. On univariable
      analysis when peak flow was categorized as 15 or greater, 10 to 14.9 and less
      than 10 ml per second, flow rates of 10 to 14.9 and less than 10 ml per second
      were associated with a significantly increased risk of incident lower urinary
      tract symptoms (HR 1.39, p = 0.011 and 1.67, p <0.001, respectively). Results
      were similar on multivariable analysis, although in the 10 to 14.9 ml per second
      group findings were no longer statistically significant (HR 1.26, p = 0.071).
      CONCLUSIONS: In men with mild to no lower urinary tract symptoms a decreased peak
      urine flow rate is independently associated with incident lower urinary tract
      symptoms. If confirmed, these men should be followed closer for incident lower
      urinary tract symptoms.

PMID- 28428111
TI  - Reproductive healthcare experiences of women with cerebral palsy.
AB  - BACKGROUND: Little is known about pregnancy rates in women with disabilities in
      general and even less is known about women with child-onset disabilities such as
      cerebral palsy (CP). HYPOTHESIS: We hypothesized that discussions about pregnancy
      with healthcare providers and pregnancy rates for woman with CP would be related
      to their functional levels. METHODS: Survey methodology was used to gather
      information about demographics, function, whether women were asked about their
      desire for children, pregnancy outcomes, and services offered during pregnancy
      and postpartum. RESULTS: Of the 375 women with CP who participated in the survey,
      76 (20%) reported 149 pregnancies resulting in 100 live births. Using Chi square
      statistics, mobility, manual dexterity, and communication function were
      significantly higher in women who were queried about or who experienced
      pregnancy. More than half of the women experienced a loss of mobility during
      pregnancy but few received referrals for physical or occupational therapy. Few
      reported screening for postpartum depression. A higher rate of Cesarean sections
      (50.4%), preterm births (12.1%), low birth weight infants (15.7%), and very low
      birth weight infants (7.1%) was reported by women with CP compared to national
      statistics. CONCLUSIONS: Pregnancy rates and discussions were related to
      functional levels. As 20% of women with CP surveyed experienced pregnancy, there
      is a need to increase awareness, education, support, and advocacy for achievement
      of optimal reproductive health. More research is needed to identify factors
      contributing to maternal and infant health in women with CP.

PMID- 28428112
TI  - Experiences and unmet needs of women with physical disabilities for pain relief
      during labor and delivery.
AB  - BACKGROUND: Childbirth is widely acknowledged as one of the most painful
      experiences most women will undergo in their lifetimes. Alleviating labor and
      delivery pain for women with physical disabilities can involve an additional
      level of complexity beyond that experienced by most women, but little research
      has explored their experiences. OBJECTIVE: The purpose of this study was to
      explore the experiences of women with physical disabilities with respect to pain
      relief during labor and delivery with the goal of informing their care. METHODS:
      Data were collected using semi-structured interviews with twenty-five women with
      physical disabilities from across the United States. RESULTS: Women expressed
      specific preferences for the method of pain relief. Some confronted systemic
      barriers in exploring their options for pain relief, while others were given a
      choice. At times, anesthesiologists lacked knowledge and experience in caring for
      women with disabilities. Conversely, some women described how the administration
      of anesthesia was meticulously planned and attributed their positive labor and
      delivery experiences to this careful planning. CONCLUSIONS: Advanced,
      individualized planning and evaluation of their options for pain relief was most
      satisfying to women and enabled them to make an informed choice. This approach is
      consistent with the recommendations of clinicians who have successfully provided
      pain relief during labor to women with complex physical disabilities. Clinicians
      who have successfully delivered babies of women with these and similar
      disabilities emphasize the importance of a team approach where the
      anesthesiologist and other specialists are involved early on in a woman's care.

PMID- 28428113
TI  - Impact of enjoyment on physical activity and health among children with
      disabilities in schools.
AB  - BACKGROUND: Enjoyment in school-based physical activity (PA) programs, such as
      recess or physical education may be important for promoting children's health,
      but there is a lack of evidence explaining how enjoyment affects health in
      children with disabilities. HYPOTHESES: Enjoyment in school-based PA programs
      will positively influence general health through participating in more daily PA,
      and this relationship will vary between younger and older children with
      disabilities. METHODS: We conducted secondary analysis of data from the 2012
      National Youth Fitness Survey. The sample included 241 children with disabilities
      (age 5-15 years; 129 boys and 112 girls) identified using three criteria: (a)
      having an impairment, health problem and mobility limitations; (b) needing
      special equipment; or (c) receiving special education services. Variables
      extracted were the number of days per week participating for at least 60 min in
      PA a day; general perceived health; enjoyment in school recess (for ages 5-11 y)
      or physical education (for ages 12-15 y). Mediation analysis was conducted to
      test the research hypotheses. RESULTS: Daily PA participation significantly
      mediated the relationship between enjoyment in physical education/recess and
      general health. Children who enjoyed physical education or recess more
      participated in PA, and those who spent more days being physical active were
      healthier than their counterparts. However, this mediating relationship, when
      divided by age groups, was shown for only older group (ages 12-15 y) that
      received physical education. CONCLUSIONS: Physical educators should provide
      enjoyable PA opportunities during physical education classes for students with
      disabilities for promoting their health.

PMID- 28428114
TI  - Epigenetics: The third pillar of nitric oxide signaling.
AB  - Nitric oxide (NO), the endogenously produced free radical signaling molecule, is
      generally thought to function via its interactions with heme-containing proteins,
      such as soluble guanylyl cyclase (sGC), or by the formation of protein adducts
      containing nitrogen oxide functional groups (such as S-nitrosothiols, 3
      nitrotyrosine, and dinitrosyliron complexes). These two types of interactions
      result in a multitude of down-stream effects that regulate numerous functions in
      physiology and disease. Of the numerous purported NO signaling mechanisms,
      epigenetic regulation has gained considerable interest in recent years. There is
      now abundant experimental evidence to establish NO as an endogenous epigenetic
      regulator of gene expression and cell phenotype. Nitric oxide has been shown to
      influence key aspects of epigenetic regulation that include histone
      posttranslational modifications, DNA methylation, and microRNA levels. Studies
      across disease states have observed NO-mediated regulation of epigenetic protein
      expression and enzymatic activity resulting in remodeling of the epigenetic
      landscape to ultimately influence gene expression. In addition to the well
      established pathways of NO signaling, epigenetic mechanisms may provide much
      needed explanations for poorly understood context-specific effects of NO. These
      findings provide more insight into the molecular mechanisms of NO signaling and
      increase our ability to dissect its functional role(s) in specific micro
      environments in health and disease. This review will summarize the current state
      of NO signaling via epigenetic mechanisms (the "third pillar" of NO signaling).

PMID- 28428115
TI  - p300 and C/EBPbeta-regulated IKKbeta expression are involved in thrombin-induced
      IL-8/CXCL8 expression in human lung epithelial cells.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are common chronic lung
      inflammatory diseases. Thrombin and interleukin (IL)-8/C-X-C chemokine ligand 8
      (CXCL8) play critical roles in lung inflammation. Our previous study showed that
      c-Src-dependent IkappaB kinase (IKK)/IkappaBalpha/nuclear factor (NF)-kappaB and
      mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal
      regulated kinase (ERK)/ribosomal S6 protein kinase (RSK)-dependent CAAT/enhancer
      binding protein beta (C/EBPbeta) activation are involved in thrombin-induced IL
      8/CXCL8 expression in human lung epithelial cells. In this study, we aimed to
      investigate the roles of p300 and C/EBPbeta-reliant IKKbeta expression in
      thrombin-induced IL-8/CXCL8 expression. Thrombin-induced increases in IL-8/CXCL8
      luciferase activity and IL-8/CXCL8 release were inhibited by p300 small
      interfering (siRNA). Thrombin-caused histone H3 acetylation was attenuated by
      p300 siRNA. Stimulation of cells with thrombin for 12h resulted in increases in
      IKKbeta expression and phosphorylation in human lung epithelial cells. However,
      thrombin did not affect p65 expression. Moreover, 12h of thrombin stimulation
      produced increases in IKKbeta expression and phosphorylation, and IkappaBalpha
      phosphorylation, which were inhibited by C/EBPbeta siRNA. Finally, treatment of
      cells with thrombin caused increases in p300 and C/EBPbeta complex formation, p65
      and C/EBPbeta complex formation, and recruitment of p300, p65, and C/EBPbeta to
      the IL-8/CXCL8 promoter. These results imply that p300-dependent histone H3
      acetylation and C/EBPbeta-regulated IKKbeta expression contribute to thrombin
      induced IL-8/CXCL8 expression in human lung epithelial cells. Results of this
      study will help clarify C/EBPbeta signaling pathways involved in thrombin-induced
      IL-8/CXCL8 expression in human lung epithelial cells.

PMID- 28428116
TI  - Cycloastragenol improves hepatic steatosis by activating farnesoid X receptor
      signalling.
AB  - Non-alcoholic fatty liver disease (NAFLD) has become a global health problem.
      However, there is no approved therapy for NAFLD. Farnesoid X receptor (FXR) is a
      potential drug target for treatment of NAFLD. In an attempt to screen FXR
      agonists, we found that cycloastragenol (CAG), a natural occurring compound in
      Astragali Radix, stimulated FXR transcription activity. In animal studies, we
      demonstrated that CAG treatment resulted in obvious reduction of high-fat diet
      induced lipid accumulation in liver accompanied by lowered blood glucose, serum
      triglyceride levels and hepatic bile acid pool size. The stimulation of FXR
      signalling by CAG treatment in DIO mice was confirmed via gene expression and
      western blot analysis. Molecular docking data further supported the interaction
      of CAG and FXR. In addition, CAG alleviated hepatic steatosis in methionine and
      choline deficient L-amino acid diet (MCD) induced non-alcoholic steatohepatitis
      (NASH) mice. Our data suggest that CAG ameliorates NAFLD via the enhancement of
      FXR signalling.

PMID- 28428117
TI  - Cellular non-linear network model of microbial fuel cell.
AB  - A cellular non-linear network (CNN) is a uniform regular array of locally
      connected continuous-state machines, or nodes, which update their states
      simultaneously in discrete time. A microbial fuel cell (MFC) is an electro
      chemical reactor using the metabolism of bacteria to drive an electrical current.
      In a CNN model of the MFC, each node takes a vector of states which represent
      geometrical characteristics of the cell, like the electrodes or impermeable
      borders, and quantify measurable properties like bacterial population, charges
      produced and hydrogen ion concentrations. The model allows the study of integral
      reaction of the MFC, including temporal outputs, to spatial disturbances of the
      bacterial population and supply of nutrients. The model can also be used to
      evaluate inhomogeneous configurations of bacterial populations attached on the
      electrode biofilms.

PMID- 28428118
TI  - On plant roots logical gates.
AB  - Theoretical constructs of logical gates implemented with plant roots are
      morphological computing asynchronous devices. Values of Boolean variables are
      represented by plant roots. A presence of a plant root at a given site symbolises
      the logical True, an absence the logical False. Logical functions are calculated
      via interaction between roots. Two types of two-inputs-two-outputs gates are
      proposed: a gate <x, y>-><xy, x+y> where root apexes are guided by gravity and a
      gate <x,y>-><x-y,x> where root apexes are guided by humidity. We propose a design
      of binary half-adder based on the gates.

PMID- 28428119
TI  - Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: A
      systematic review.
AB  - BACKGROUND: Immunotherapy initiated early after first presentation of relapsing
      remitting multiple sclerosis is associated with improved long-term outcomes. One
      can therefore speculate that early initiation of highly effective
      immunotherapies, with an average efficacy that is superior to the typical first
      line therapies, could further improve relapse and disability outcomes. However,
      the most common treatment strategy is to commence first-line therapies, followed
      by treatment escalation in patients who continue to experience on-treatment
      disease activity. While this monitoring approach is logical, the current lack of
      effective regenerative or remyelinating therapies behoves us to consider high
      efficacy treatment strategies from disease onset (including induction therapy) in
      order to prevent irreversible disability. OBJECTIVE: In this systematic review,
      we evaluate the effect of high-efficacy immunotherapies at different stages of
      MS. METHODS: A systematic review of literature reporting outcomes of treatment
      with fingolimod, natalizumab or alemtuzumab at different stages of MS was carried
      out. RESULTS AND CONCLUSIONS: Twelve publications reporting relevant information
      were included in the systematic review. The literature suggests that treatment
      with high-efficacy immunotherapies is more potent in suppressing relapse activity
      when initiated early vs. with a delay after the MS diagnosis. The evidence
      reported for disability and MRI outcomes is inconclusive.

PMID- 28428120
TI  - Pathogenesis of immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T
      cell response, notably supported by splenic T follicular helper cells, that
      stimulates the proliferation and differentiation of autoreactive B cells. The
      antiplatelet autoantibodies they produce facilitate platelet phagocytosis by
      macrophages, essentially in the spleen. Macrophages contribute to the
      perpetuation of the auto-immune response as the main antigen-presenting cell
      during ITP. CD8+ T cells also participate to thrombocytopenia by increasing
      platelet apoptosis. Besides this peripheral platelet destruction, inappropriate
      bone marrow production also exacerbates thrombocytopenia, due to an immune
      response against megakaryocytes. Moreover, the level of circulating
      thrombopoietin, the main growth factor of megakaryocytes, is low during ITP. In
      this review, the major mechanisms leading to thrombocytopenia, the role of the
      different immune cells and the different targets of treatments are described.

PMID- 28428122
TI  - Challenges in the management of Chagas disease in Latin-American migrants in
      Europe.
AB  - Chagas disease is endemic in Latin America. Due to migration the infection has
      crossed borders and it is estimated that 68,000-120,000 people with Chagas
      disease are currently living in Europe and 30% of them may develop visceral
      involvement. However, up to 90% of Chagas disease cases in Europe remain
      undiagnosed. The challenges which have to be overcome in Chagas disease in non
      endemic countries are focused on related downing barriers to health care access,
      and related to screening, diagnostic tools and therapeutic management. The aim of
      this review is to highlight how healthcare management for Latin American migrants
      with Chagas disease in Europe may be improved. Medical literature was searched
      using PubMed. No limits were placed with respect to the language or date of
      publication although most of the articles selected were articles published in the
      last five years. Chosen search terms were "Chagas disease" AND ("migrants" OR
      "screening" OR "transmission" OR "treatment"; OR "knowledge" OR "non-endemic
      countries"); migrants AND ("Public health" OR "Health Service Accessibility" OR
      "Delivery of Health care"); and "Congenital Chagas disease". Healthcare
      management of migrant populations with Chagas disease in Europe has to be
      improved: -Surveillance programmes are needed to measure the burden of the
      disease; -screening programmes are needed; -administrative and cultural barriers
      in the access to health care for migrants should be reduced; -education
      programmes on Chagas disease should be performed -research on new diagnostic
      tools and therapeutic options are required. This review highlights the needs of
      profound changes in the health care of Latin American migrants with Chagas
      disease in Europe.

PMID- 28428121
TI  - The blood brain barrier and neuropsychiatric lupus: new perspectives in light of
      advances in understanding the neuroimmune interface.
AB  - Experts have previously postulated a linkage between lupus associated vascular
      pathology and abnormal brain barriers in the immunopathogenesis of
      neuropsychiatric lupus. Nevertheless, there are some discrepancies between the
      experimental evidence, or its interpretation, and the working hypotheses
      prevalent in this field; specifically, that a primary contributor to
      neuropsychiatric disease in lupus is permeabilization of the blood brain barrier.
      In this commonly held view, any contribution of the other known brain barriers,
      including the blood-cerebrospinal fluid and meningeal barriers, is mostly
      excluded from the discussion. In this review we will shed light on some of the
      blood brain barrier hypotheses and try to trace their roots. In addition, we will
      suggest new research directions to allow for confirmation of alternative
      interpretations of the experimental evidence linking the pathology of intra
      cerebral vasculature to the pathogenesis of neuropsychiatric lupus.

PMID- 28428123
TI  - Transvaginal ultrasound-guided embryo transfer in IVF.
AB  - OBJECTIVES: To determine whether transvaginal ultrasound-guided embryo transfer
      is a technique that can be used routinely, whether it improves IVF outcomes and
      whether it makes difficult transfers easier and more successful. MATERIAL AND
      METHOD: Non-randomized retrospective study conducted between 2012 and 2016 in the
      fertility center of the Diaconesses-Croix St-Simon hospital group. The outcomes
      of 3910 transfers, performed by 5 senior operators, under transabdominal
      ultrasound guidance are compared with those of 800 transfers, performed by 1
      senior operator under transvaginal ultrasound guidance. The criteria studied are
      the feasibility of the technique and the percentage of pregnancies per transfer
      in the two populations described, as well as in the difficult and very difficult
      transfer populations. RESULTS: All the transfers were feasible under transvaginal
      ultrasound guidance without the use of forceps or additional instruments. The
      percentage of pregnancies per transfer is significantly increased, when the
      transfer is performed under transvaginal ultrasound guidance compared with that
      performed under transabdominal ultrasound guidance, in the general population
      (38%, n=800 vs 30%, n=3910; P 0.0004) and in the reference population
      characterized by age <38 years and >6 oocytes collected per puncture (45%, n=490
      vs 36%, n=1968; P 0.002). The percentage of pregnancies per transfer (P/T) is not
      significantly different in the populations of easy transfers (n 695, 38% P/T),
      difficult transfers (n 58, 46% P/T; P=ns) and very difficult transfers (n 47, 34%
      P/T; P=ns). CONCLUSIONS: Embryo transfer is a key stage in IVF, in which the
      quality of performance determines the outcome. In this study, transvaginal
      ultrasound guidance of the transfer, which is the reference procedure in
      gynaecological imaging, significantly increases the percentage of pregnancies per
      transfer, both in the general population and in the reference population,
      compared with transfers performed under transabdominal ultrasound guidance.
      Transvaginal ultrasound facilitates the performance of difficult transfers and in
      particular achieves outcomes in these situations that are not significantly
      different from those of easy transfers. Visual monitoring of transcervical
      passage, which is rendered more precise and less traumatic and precision of
      embryo deposition are the factors that probably account for the improvement in
      outcomes.

PMID- 28428124
TI  - Induced labour at term and breech presentation: Experience of a level IIB French
      maternity.
AB  - : Data from the literature on induction of labour in breech presentation are rare
      and no conclusions can be drawn for this procedure. OBJECTIVES: To evaluate
      obstetrical and neonatal prognosis following induced labour in breech deliveries
      at term (37 to 42 weeks of gestation). METHODS: We conducted a single-centre
      retrospective case-control study in a level IIB maternity unit from 1st January
      2012 to 31st December 2015. The inclusion criteria were a singleton pregnancy and
      a breech presentation. RESULTS: A total of 235 patients were included, 178 in the
      spontaneous labour group (group A), 57 in the induced labour group (whatever the
      procedure used: oxytocin or prostaglandin) (group B). There was no significant
      difference concerning the vaginal delivery rate between group A and group B
      (88.2% versus 91.2%). Both groups were also similar for transfers to neonatal
      units (10.7% versus 15.8%), pH<7.0 (1.1% versus 1.8%) and 5-minute Apgar<4 (1.1%
      versus 1.7%). There were no neonatal deaths or transfers to neonatal intensive
      care units. CONCLUSION: Induced labour in breech presentation is feasible with a
      vaginal delivery rate similar to that in spontaneous labour and the same neonatal
      outcomes. This therapeutic option must be considered in trained obstetrical teams
      when vaginal delivery in breech presentations is not contraindicated.

PMID- 28428125
TI  - Ovarian metastasis of a malignant melanoma: A case report.
AB  - Malignant melanoma represents 3% of cancers at the woman. The metastatic
      gynecological localization are rare and ovary is an exceptional site. Prognosis
      of metastatic ovary malignant melanoma is pejorative (5% 5 years survival). We
      report a case observed in a 65-year-old patient, who developed 2 melanomas of the
      left leg and presented a right ovarian tumor during a supervision
      tomodensitometric 7 years after diagnostic initial. The immunohistochemical
      assays after annexectomy confirmed the diagnostic of ovarian metastasis. To evoke
      an ovarian metastasis localization of a malignant melanoma in front of the
      increasing incidence is a decisive for prognosis.

PMID- 28428126
TI  - Interactions of tetracyclines with ovalbumin, the main allergen protein from egg
      white: Spectroscopic and electrophoretic studies.
AB  - The interactions of tetracycline (TC), oxytetracycline (OTC) and
      chlortetracycline (CTC) with ovalbumin (OVA), the main allergen protein of egg
      white, were investigated by molecular spectroscopy and electrophoresis at three
      pH conditions (1.5, 4.6 and 7.4). Molecular and synchronous fluorescence, UV-vis
      spectroscopy, electrophoresis and 1H NMR were used to study the interaction
      process. Tetracyclines interact with ovalbumin fluorescence by a static quenching
      mechanism with non-fluorescent complex formation changing the native protein
      structure. The binding constant (Kb) ranged from 2.11*104 to 58.4*104Lmol-1, and
      corresponding thermodynamic parameters were measured at different temperatures
      and pH values. The binding process was spontaneous (DeltaG<0), and the magnitude
      of the interaction increased in the following order: TC<CTC<OTC. Hydrogen,
      electrostatic, and Van der Waals forces played a major role in stabilizing the
      complex. The distances between the donor (protein) and receptors (TC, OTC and
      CTC) were determined by FRET and varied of 2.95-3.52nm. Fe(III) and Zn(II) ions
      increase the affinities of TC and CTC for OVA, while OTC did not suffer a
      significant influence by the competitor metallic species evaluated.

PMID- 28428127
TI  - Potassium and sodium ions enhance the activity and thermostability of 1,4-alpha
      glucan branching enzyme from Geobacillus thermoglucosidasius in the presence of
      glycerol.
AB  - Metal ions are essential for the performance of metal-dependent proteins and are
      known to be important for thermophilic proteins containing a large number of
      charged residues. The performance of thermophilic proteins may be influenced by
      metal ions through electrostatic interactions between the metal ions and charged
      residues. In this study, we investigated the effects of metal ions and glycerol
      on the activity and stability of the thermophilic 1,4-alpha-glucan branching
      enzyme (abbreviated GBE; EC 2.4.1.18) from G. thermoglucosidasius STB02. The
      results indicate that K+ or Na+ enhance the performance of GBE, and that the
      addition of glycerol further increases the thermostability of GBE. The effects of
      K+ or Na+ with glycerol on the structure of GBE were further investigated using
      intrinsic fluorescence spectra and far-UV circular dichroism spectra. The results
      show that more secondary structural elements are preserved by the addition of K+
      or Na+ in the presence of glycerol. The improved maintenance of GBE structural
      elements after incubation may arise from electrostatic interactions introduced by
      the added salt, and glycerol provides a hydrophobic environment that strengthens
      these electrostatic contacts. This provides a useful perspective for
      understanding the strategy of thermophilic adaptation used by proteins with
      plenty of charged residues.

PMID- 28428128
TI  - Novel combination of zero-valent Cu and Ag nanoparticles @ cellulose acetate
      nanocomposite for the reduction of 4-nitro phenol.
AB  - A very simple and low-cost procedure has been adopted to synthesize efficient
      copper (Cu), silver (Ag) and copper-silver (Cu-Ag) mixed nanoparticles on the
      surface of pure cellulose acetate (CA) and cellulose acetate-copper oxide
      nanocomposite (CA-CuO). All nanoparticles loaded onto CA and CA-CuO presented
      excellent catalytic ability, but Cu-Ag nanoparticles loaded onto CA-CuO (Cu0
      Ag0/CA-CuO) exhibited outstanding catalytic efficiency to convert 4-nitrophenol
      (4-NP) into 4-aminophenol (4-AP) in the presence of NaBH4. Additionally, the Cu0
      Ag0/CA-CuO can be easily recovered by removing the sheet from the reaction media,
      and can be recycled several times, maintaining high catalytic ability for four
      cycles.

PMID- 28428129
TI  - Three phase partitioning, a scalable method for the purification and recovery of
      cucumisin, a milk-clotting enzyme, from the juice of Cucumis melo var.
      reticulatus.
AB  - Cucumisin [EC 3.4.21.25] was first purified from Cucumis melo var. reticulatus
      juice by three-phase partitioning (TPP). Optimum purification parameters of the
      TPP system were determined as 60% ammonium sulfate saturation with 1.0:1.25 ratio
      of crude extract: t-butanol at pH and temperature of 8.0 and 20 degrees C,
      respectively. Cucumisin was purified with 4.61 purification fold and 156%
      activity recovery. The molecular weight of the recovered cucumisin was determined
      as 68.4kDa and its isoelectric point is 8.7. Optimum pH and temperature of
      cucumisin were pH 9.0 and 60-70 degrees C, respectively. The protease was very
      stable at 20-70 degrees C and a pH range of 2.0-12.0. Km and Vmax constants were
      2.24+/-0.22mgmL-1 and 1048+/-25MU Mmin-1, respectively. The enzyme was stable
      against numerous metal ions and its activity was highly enhanced by Ca2+, Mg2+,
      and Mn+2. Cucumisin activity was 2.35-folds increased in the presence of 5mM of
      CaCl2. It was inactivated by Co2+, Cd2+, Zn2+ and Fe2+ and dramatically by PMSF.
      Cucumisin milk-clotting activity was highly stable when stored under freezing (
      20 degrees C) compared at 4 degrees C and 25 degrees C. Finally, TPP revealed to
      be a useful strategy to concentrate and purify cucumisin for its use as a milk
      clotting enzyme for cheese-making.

PMID- 28428131
TI  - Human Dermal Fibroblast Subpopulations Display Distinct Gene Signatures Related
      to Cell Behaviors and Matrisome.

PMID- 28428130
TI  - Development and Validation of an Algorithm to Accurately Identify Atopic Eczema
      Patients in Primary Care Electronic Health Records from the UK.
AB  - Electronic health records hold great promise for clinical and epidemiologic
      research. Undertaking atopic eczema (AE) research using such data is challenging
      because of its episodic and heterogeneous nature. We sought to develop and
      validate a diagnostic algorithm that identifies AE cases based on codes used for
      electronic records used in the UK Health Improvement Network. We found that at
      least one of five diagnosis codes plus two treatment codes for any skin-directed
      therapy were likely to accurately identify patients with AE. To validate this
      algorithm, a questionnaire was sent to the physicians of 200 randomly selected
      children and adults. The primary outcome, positive predictive value for a
      physician-confirmed diagnosis of AE, was 86% (95% confidence interval = 80-91).
      Additional criteria increased the PPV up to 95% but would miss up to 89% of
      individuals with physician-confirmed AE. The first and last entered diagnosis
      codes for individuals showed good agreement with the physician-confirmed age at
      onset and last disease activity; the mean difference was 0.8 years (95%
      confidence interval = -0.3 to 1.9) and -1.3 years (95% confidence interval = -2.5
      to -0.1), respectively. A combination of diagnostic and prescription codes can be
      used to reliably estimate the diagnosis and duration of AE from The Health
      Improvement Network primary care electronic health records in the UK.

PMID- 28428132
TI  - Novel properties of Hippophae rhamnoides L. twig and leaf extracts - anti
      virulence action and synergy with antifungals studied in vitro on Candida spp.
      model.
AB  - Original, chemically characterized Sea buckthorn (SBT) twig and leaf extracts
      were in vitro studied in terms of anti-Candida activity. Minimum inhibitory
      concentrations (MICs) of the extracts against C. albicans ATCC 10231 ranged: 250
      MUg/ml (twig), 31.5 MUg/ml (leaf), and against C. glabrata G1 (clinical isolate) 
      15.6 MUg/ml (twig), 3.9 MUg/ml (leaf). Next the extracts have been used at their
      subMIC. Both extracts significantly enhanced activity of fluconazole (FLC) and
      caspofungin (CAS) against C. albicans and increased their efficacy against C.
      glabrata, measured by an agar dilution assay combined with the E-test. The
      extracts inhibited C. albicans morphogenesis such as germ tube and hyphae
      formation as well as invasion to the "Spider" Agar. Antiadhesive and anti-biofilm
      activities of the extracts were evaluated by Alamar Blue reduction assay. It
      showed not significant reduction in the degree of cell adhesion (by 10-15%) but
      noticeable decrease of biofilm formation (by 80% in the case of SBT-twig
      extract). In conclusion, this study provided the evidence that SBT extracts, used
      at non-cytotoxic concentrations for the fibroblasts (IC50 from 664.8 MUg/ml to
      1060.4 MUg/ml), targeted some of Candida spp. virulence factors essential for the
      establishment of the infection. SBT twigs, previously regarded as waste material,
      were shown to be also a valuable source of the substances with promising
      antimicrobial activity.

PMID- 28428133
TI  - Epidemiological study of common diseases and their risk factors in camels in
      South Punjab, Pakistan.
AB  - Bacteriological study of mastitis along with common blood protozoan diseases were
      studied in dromedary camels in Cholistan, Dera Ismail Khan and Rahim Yar Khan
      districts in South Punjab, Pakistan. For this purpose 300 camels were sampled
      randomly at different common grazing and watering point. For study of blood
      parasites clinically suspected and apparently healthy camels, 150 each, were
      sampled. An overall prevalence of 15%and 5% was recorded for trypanosomiasis and
      Anaplasmosis respectively. Trypanosoma evansi was identified with 280 bp product
      on polymerase chain reaction test. There was significant (P < 0.05) decline in
      the values of total erythrocyte counts, hemoglobin concentration, packed cell
      volume, serum total proteins and albumin while erythrocyte sedimentation rate was
      increased in infected camels as compared to healthy ones. Aspartate
      aminotransferase, alanine aminotransferase, gamma glutamyltransferase and
      alkaline phosphatase were also significantly increased in blood protozoan the
      infected animals. Milk samples for bacteriology were collected from healthy
      lactating camels (n = 100). Information about different risk factors were
      gathered on designed performa. Subclinical mastitis on surf field test was
      recorded in 42% camels while 2% cases of clinical mastitis were recorded.
      Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae,
      Bacillus cereus and. Corynebacterium kutscheri were isolated with characteristic
      beta and alpha hemolysis patterns. Chi-square analysis showed significant
      difference as p < 0.05 among various species of bacteria (chi2 = 21.649, P-Value
      = 0.0001, df = 3). Antibiogram showed Gentamicin, Norfloxacin, Oxytetracycline as
      most effective therapy for mastitis in camel.

PMID- 28428134
TI  - Use of physiological biomarkers in diagnosis along with field trials of different
      trypanisidal drugs in camels of Cholistan desert.
AB  - The point prevalence of trypanosomiasis with different physiological biomarkers
      along with evaluation of the most responsive trypanosidal drug against
      trypanosomiasis under field conditions was studied. For this purpose a total of
      300 free range camels were selected at different grazing and watering point in
      Cholistan desert. The study population of camels included 150 clinically
      suspected camels for trypanosomiasis and 150 healthy camels with normal
      temperature, pulse and respiration. For therapeutic trials 36 positively
      diagnosed animals were randomly divided into three experimental groups for
      therapeutic trials. Group A was treated with Imidocarb dipropionate (ID) @ 1.2 mg
      kg-1 body weight; Group B was treated with Diaminazine aceturate (DA) @ 3.5 mg kg
      1 body weight and Group C was treated with Isometamidium chloride hypochloride
      (IC) @ 0.75 mg kg-1 body weight of camels. Data on risk factors of age,sex,
      ectoparasites, housing was also collected. Results revealed an overall 15% point
      prevalence of trypanosomiasis. There was significant (P < 0.05) decline in the
      values of physiological biomarkers of total erythrocyte counts, hemoglobin
      concentration, packed cell volume, serum total proteins and albumin while
      erythrocyte sedimentation rate was increased in infected camels as compared to
      healthy ones. Different hepatic enzymes including aspartate aminotransferase,
      alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase were
      also significantly increased in the infected animals. Therapeutic trials
      indicated that Isometamidium chloride hypochloride (IC) was more effective than
      Imidocarb dipropionate (ID) and Diaminazine aceturate (DA). It is concluded that
      haemato-biochemical parameters were important physiological biomarkers and IC was
      the most responsive therapeutic agent against trypanosomiasis in camels in field
      conditions. The risk factors analysis showed older camels (>5 years) showed
      highest infection while infection was found to be lowest in less than 1 year age
      group.

PMID- 28428135
TI  - The immunotoxicological pattern of subchronic and chronic benzene exposure in
      rats.
AB  - Exposure to benzene and its inevitable metabolites can result in deleterious
      effects on human health, including lymphocytopenia, hematotoxicity and cancer.
      However, the duration of exposure might alter the effects including immune
      consequences. The aim of this study was to determine whether benzene could
      modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A,
      in rats, at different exposure durations. 386 Wistar rats were assigned into
      control and treatment groups which were subdivided into groups for 45, 90 and
      135days for 0,6mL/kg of drinking water mixed benzene treatment. The percentage of
      CD3+, CD4+, CD8+ spleen lymphocytes was defined using the flow cytometer.
      Interleukin (IL)-4, IL-6, IL-10 and interferon-gamma, in supernatants of
      splenocyte cultures stimulated with Concanavalin A, were assessed by enzyme
      linked immunosorbent assay (ELISA) technique. The decrease in the total
      lymphocyte and T cell counts were associated with increased benzene exposure
      duration. Th2-type cytokine, IL-4 significantly increased, whereas IL-6, CD4+T
      cells, CD4+/CD8+ ratio and CD3+ T cells decreased. Despite the positive
      correlation between benzene toxicity and indicated increased immune responses, 45
      day exposure to benzene appeared to be the most sensitive time point for
      evaluating benzene cytotoxicity.

PMID- 28428136
TI  - Hesperetin derivative-14 alleviates inflammation by activating PPAR-gamma in mice
      with CCl4-induced acute liver injury and LPS-treated RAW264.7 cells.
AB  - Hesperetin is a flavanone glycoside compound naturally occurring in the fruit
      peel of Citrusaurantium L. (Rutaceae). Previous studies revealed that hesperetin
      possesses various pharmacological effects, including anti-inflammation, anti
      tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD
      14) is a derivative of hesperetin improved in water solubility and
      bioavailability. In this study, we indicated that HD-14 (2MUM) significantly
      attenuated inflammation in LPS-treated RAW264.7 cells, besides, HD-14 (100mg/kg)
      exhibited hepato-protective effects and anti-inflammatory effects on C57BL/6J
      mice with CCl4-induced acute liver injury. In addition, it was demonstrated that
      HD-14 dramatically up-regulated the expression of PPAR-gamma in vivo and in
      vitro. Interestingly, over-expression of PPAR-gamma had anti-inflammatory effects
      on the expressions of TNF-alpha, IL-6, and IL-1beta, whereas, knockdown of PPAR
      gamma with small interfering RNA had pro-inflammatory effects in LPS-treated
      RAW264.7 cells. Thus, our findings demonstrated that HD-14 alleviated
      inflammation by activating PPAR-gamma expression at least in part. Further
      studies founded that HD-14 remarkably inhibited the expression of p-JAK1 and p
      STAT1 through up-regulating PPAR-gamma. Together, these results suggested that HD
      14 served as an activator of PPAR-gamma and the JAK1/STAT1 signaling pathway may
      be involved in the progress of inflammation. Collectively, HD-14 may be utilized
      as a potential anti-inflammation monomeric compound in the treatment of acute
      liver injury.

PMID- 28428137
TI  - JWA antagonizes paraquat-induced neurotoxicity via activation of Nrf2.
AB  - Paraquat (PQ), a widely used environmental toxin in agriculture, contributes to
      the onset and progression of Parkinson's disease (PD) by damaging neurons. The
      JWA gene, also known as ARL6IP5, exerts a protective effect on degenerating
      dopamine (DA) neurons. However, the roles of JWA in PQ-induced neuronal damage
      are still unknown. In our study, two neuronal cell lines (HT-22 and SH-SY5Y) and
      neuron-specific JWA knockout (JWA-nKO) and age-matched wild-type (JWA-nWT) mice
      were subjected to PQ treatment. The results indicate that PQ administration
      triggers the upregulation of JWA. Elevated expression of JWA rescues the
      accumulation of reactive oxygen species (ROS) while increasing glutathione (GSH)
      and glutathione peroxidase (GPx) levels under PQ exposure. Further investigations
      revealed that the protective effect of JWA mostly involves regulation of the
      MEK/PI3K-Nrf2 axis. Our results suggest that JWA may be a novel target for the
      prevention and treatment of PQ-induced PD.

PMID- 28428138
TI  - Pregnane X receptor regulates the AhR/Cyp1A1 pathway and protects liver cells
      from benzo-[alpha]-pyrene-induced DNA damage.
AB  - Pregnane X receptor (PXR) plays an important role in protecting cells from
      mutagenic DNA damages induced by endogenous and exogenous toxicants. This
      protective function is often attributed to the PXR-regulated metabolic
      detoxification. Here we report a novel potential mechanism that PXR reduces benzo
      [alpha]-pyrene(BaP)-induced DNA damage through inhibiting the transcriptional
      activity of aryl hydrocarbon receptor (AhR) which plays a pivotal role in the
      bioactivation of BaP. We have utilized three well-characterized cell lines, i.e.
      Hepa1c1c7, AhR +/+; Bpr lacks AhR obligatory partner ARNT; Tao, lacks AhR, to
      analyze pivotal role of AhR/ARNT complex in mediating the BaP-induced DNA damages
      using comet assay (single-cell gel electrophoresis). We found that PXR activation
      could significantly inhibit BaP-induced DNA damage in the HepG2 cells as well as
      mouse hepatocytes. Using PXR-null and wild type mouse hepatocytes we showed that
      PXR activation by pregnenolone 16alpha-carbonitrile (PCN) significantly inhibited
      BaP-induced DNA damage and this protective effect was abolished in PXR-null
      hepatocytes. Mechanistically, PXR activation inhibited expression of AhR-target
      genes for CYP1A1, CYP1B1 and CYP1A2 that are required for BaP biotransformation
      in cultured liver cells, or in the livers of C57BL/6J mice. Using an AhR
      responsive reporter assay as well as chromatin immunoprecipitation assay we found
      that PXR activation transcriptionally represses AhR-regulated gene expression.
      Furthermore, we found that PXR directly bound AhR at its DNA-binding domain, and
      this association may play a role in preventing of the AhR from binding to its
      target genes as shown in the ChIP assay. Taken together, our study has revealed a
      novel mechanism by which PXR protects liver cells from BaP-induced DNA damage
      through inhibiting the BaP biotransformation.

PMID- 28428139
TI  - Reporting of Bayesian analysis in epidemiologic research should become more
      transparent.
AB  - OBJECTIVES: The objective of this systematic review is to investigate the use of
      Bayesian data analysis in epidemiology in the past decade and particularly to
      evaluate the quality of research papers reporting the results of these analyses.
      STUDY DESIGN AND SETTING: Complete volumes of five major epidemiological journals
      in the period 2005-2015 were searched via PubMed. In addition, we performed an
      extensive within-manuscript search using a specialized Java application. Details
      of reporting on Bayesian statistics were examined in the original research papers
      with primary Bayesian data analyses. RESULTS: The number of studies in which
      Bayesian techniques were used for primary data analysis remains constant over the
      years. Though many authors presented thorough descriptions of the analyses they
      performed and the results they obtained, several reports presented incomplete
      method sections and even some incomplete result sections. Especially, information
      on the process of prior elicitation, specification, and evaluation was often
      lacking. CONCLUSION: Though available guidance papers concerned with reporting of
      Bayesian analyses emphasize the importance of transparent prior specification,
      the results obtained in this systematic review show that these guidance papers
      are often not used. Additional efforts should be made to increase the awareness
      of the existence and importance of these checklists to overcome the controversy
      with respect to the use of Bayesian techniques. The reporting quality in
      epidemiological literature could be improved by updating existing guidelines on
      the reporting of frequentist analyses to address issues that are important for
      Bayesian data analyses.

PMID- 28428140
TI  - Automated annotation and classification of BI-RADS assessment from radiology
      reports.
AB  - The Breast Imaging Reporting and Data System (BI-RADS) was developed to reduce
      variation in the descriptions of findings. Manual analysis of breast radiology
      report data is challenging but is necessary for clinical and healthcare quality
      assurance activities. The objective of this study is to develop a natural
      language processing (NLP) system for automated BI-RADS categories extraction from
      breast radiology reports. We evaluated an existing rule-based NLP algorithm, and
      then we developed and evaluated our own method using a supervised machine
      learning approach. We divided the BI-RADS category extraction task into two
      specific tasks: (1) annotation of all BI-RADS category values within a report,
      (2) classification of the laterality of each BI-RADS category value. We used one
      algorithm for task 1 and evaluated three algorithms for task 2. Across all
      evaluations and model training, we used a total of 2159 radiology reports from 18
      hospitals, from 2003 to 2015. Performance with the existing rule-based algorithm
      was not satisfactory. Conditional random fields showed a high performance for
      task 1 with an F-1 measure of 0.95. Rules from partial decision trees (PART)
      algorithm showed the best performance across classes for task 2 with a weighted F
      1 measure of 0.91 for BIRADS 0-6, and 0.93 for BIRADS 3-5. Classification
      performance by class showed that performance improved for all classes from Naive
      Bayes to Support Vector Machine (SVM), and also from SVM to PART. Our system is
      able to annotate and classify all BI-RADS mentions present in a single radiology
      report and can serve as the foundation for future studies that will leverage
      automated BI-RADS annotation, to provide feedback to radiologists as part of a
      learning health system loop.

PMID- 28428141
TI  - Temporal impact of the vascular wilt pathogen Verticillium dahliae on tomato root
      proteome.
AB  - : The soil-borne fungus Verticillium dahliae is the causal agent of wilting
      disease and affects a wide range of plant species worldwide. Here, we report on
      the time-resolved analysis of the tomato root proteome in response to fungal
      colonization. Tomato (Solanum lycopersicum cv. Hildares) was inoculated with V.
      dahliae at the two-leaf stage and roots were harvested at 7, 14 and 21 days post
      inoculation (dpi). In order to identify proteins related to the fungal spread at
      the different time points, a subsequent proteome analysis by two-dimensional
      differential gel electrophoresis (2D-DIGE) was conducted on samples from three
      independent experiments. Hierarchical clustering and k-means clustering of
      identified proteins distinguished early and late responses to fungal
      colonization. The results underline that plant defense and adaptation responses
      are timely coordinated. Proteins involved in oxidative stress were down-regulated
      at 7 dpi but induced 21 dpi indicating versatile reactive oxygen species
      signaling interacting with salicylic acid defence signaling at that stage of
      infection. Drought-stress proteins were induced at 21 dpi, reflecting the
      beginning of wilting symptoms. Notably, two proteins involved in energy
      generating pathways were induced throughout all sampling dates and may reflect
      the increase in metabolic activity to maintain root growth and, concurrently,
      activate defense responses. BIOLOGICAL SIGNIFICANCE: Mounting of defense
      responses requires a substantial flux of carbon and nitrogen from primary to
      secondary metabolites. In-depth understanding of these key metabolic pathways
      required for growth and defense responses, especially at proteome level, will
      allow the development of breeding strategies for crops where Verticillium
      tolerance is absent. Our data show early and late responses of tomato root
      proteins towards pathogen infection and identify primary metabolism enzymes
      affected by V. dahliae. Those proteins represent candidates for plant
      improvement.

PMID- 28428142
TI  - Increased Rate of Adenoma Detection Associates With Reduced Risk of Colorectal
      Cancer and Death.
AB  - BACKGROUND & AIMS: The quality of endoscopists' colonoscopy performance is
      measured by adenoma detection rate (ADR). Although ADR is associated inversely
      with interval colorectal cancer and colorectal cancer death, the effects of an
      increasing ADR have not been shown. We investigated whether increasing ADRs from
      individual endoscopists is associated with reduced risks of interval colorectal
      cancer and subsequent death. METHODS: We performed a prospective cohort study of
      individuals who underwent a screening colonoscopy within the National Colorectal
      Cancer Screening Program in Poland, from January 1, 2004, through December 31,
      2008. We collected data from 146,860 colonoscopies performed by 294 endoscopists,
      with each endoscopist having participated at least twice in annual editions of
      primary colonoscopy screening. We used annual feedback and quality benchmark
      indicators to improve colonoscopy performance. We used ADR quintiles in the whole
      data set to categorize the annual ADRs for each endoscopist. An increased ADR was
      defined as an increase by at least 1 quintile category, or the maintenance of the
      highest category in subsequent screening years. Multivariate frailty models were
      used to evaluate the effects of increased ADR on the risk of interval colorectal
      cancer and death. RESULTS: Throughout the enrollment period, 219 endoscopists
      (74.5%) increased their annual ADR category. During 895,916 person-years of
      follow-up evaluation through the National Cancer Registry, we identified 168
      interval colorectal cancers and 44 interval cancer deaths. An increased ADR was
      associated with an adjusted hazard ratio for interval colorectal cancer of 0.63
      (95% confidence interval [CI], 0.45-0.88; P = .006), and for cancer death of 0.50
      (95% CI, 0.27-0.95; P = .035). Compared with no increase in ADR, reaching or
      maintaining the highest quintile ADR category (such as an ADR > 24.56%) decreased
      the adjusted hazard ratios for interval colorectal cancer to 0.27 (95% CI, 0.12
      0.63; P = .003), and 0.18 (95% CI, 0.06-0.56; P = .003), respectively.
      CONCLUSIONS: In a prospective study of individuals who underwent screening
      colonoscopy within a National Colorectal Cancer Screening Program, we associated
      increased ADR with a reduced risk of interval colorectal cancer and death.

PMID- 28428143
TI  - High-Quality Diets Associate With Reduced Risk of Colorectal Cancer: Analyses of
      Diet Quality Indexes in the Multiethnic Cohort.
AB  - BACKGROUND & AIMS: Healthy eating patterns assessed by diet quality indexes
      (DQIs) have been related to lower risk of colorectal cancer-mostly among whites.
      We investigated the associations between 4 DQI scores (the Healthy Eating Index
      2010 [HEI-2010], the Alternative Healthy Eating Index 2010 [AHEI-2010], the
      alternate Mediterranean diet score [aMED], and the Dietary Approaches to Stop
      Hypertension score) and colorectal cancer risk in the Multiethnic Cohort.
      METHODS: We analyzed data from 190,949 African American, Native Hawaiian,
      Japanese American, Latino, and white individuals, 45 to 75 years old, who entered
      the Multiethnic Cohort study from 1993 through 1996. During an average 16 years
      of follow-up, 4770 invasive colorectal cancer cases were identified. RESULTS:
      Scores from all 4 DQIs associated inversely with colorectal cancer risk; higher
      scores associated with decreasing colorectal cancer risk (all P's for trend <=
      .003). Associations were not significant for AHEI-2010 and aMED scores in women
      after adjustment for covariates: for the highest vs lowest quintiles, the hazard
      ratio for the HEI-2010 score in men was 0.69 (95% confidence interval [CI], 0.59
      0.80) and in women was 0.82 (95% CI, 0.70-0.96); for the AHEI-2010 score the
      hazard ratio in men was 0.75 (95% CI, 0.65-0.85) and in women was 0.90 (95% CI,
      0.78-1.04); for the aMED score the hazard ratio in men was 0.84 (95% CI, 0.73
      0.97) and in women was 0.96 (95% CI, 0.82-1.13); for the Dietary Approaches to
      Stop Hypertension score the hazard ratio in men was 0.75 (95% CI, 0.66-0.86) and
      in women was 0.86 (95% CI, 0.75-1.00). Associations were limited to the left
      colon and rectum for all indexes. The inverse associations were less strong in
      African American individuals than in the other 4 racial/ethnic groups.
      CONCLUSIONS: Based on an analysis of data from the Multiethnic Cohort Study, high
      quality diets are associated with a lower risk of colorectal cancer in most
      racial/ethnic subgroups.

PMID- 28428144
TI  - Association of Aflatoxin and Gallbladder Cancer.
AB  - BACKGROUND & AIMS: Aflatoxin, which causes hepatocellular carcinoma, may also
      cause gallbladder cancer. We investigated whether patients with gallbladder
      cancer have higher exposure to aflatoxin than patients with gallstones. METHODS:
      We measured aflatoxin B1 (AFB1)-lysine adducts in plasma samples from the
      Shanghai Biliary Tract Cancer case-control study, conducted from 1997 through
      2001. We calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) and the population-attributable fraction for 209 patients with
      gallbladder cancer and gallstones vs 250 patients with gallstones without cancer
      (controls). In 54 patients with gallbladder cancer, tumor tissue was examined for
      the R249S mutation in TP53, associated with aflatoxin exposure, through targeted
      sequencing. RESULTS: The AFB1-lysine adduct was detected in 67 (32%) of 209
      patients with gallbladder cancer and 37 (15%) of the 250 controls (chi2 P <
      .0001), almost threefold more patients with gallbladder cancer than controls (OR,
      2.71; 95% CI, 1.70-4.33). Among participants with detectable levels of AFB1
      lysine, the median level of AFB1-lysine was 5.4 pg/mg in those with gallbladder
      cancer, compared with 1.2 pg/mg in controls. For patients in the fourth quartile
      of AFB1-lysine level vs the first quartile, the OR for gallbladder cancer was
      7.61 (95% CI, 2.01-28.84). None of the 54 gallbladder tumors sequenced were found
      to have the R249S mutation in TP53. The population-attributable fraction for
      cancer related to aflatoxin was 20% (95% CI, 15%-25%). CONCLUSIONS: In a case
      control study of patients with gallbladder cancer and gallstones vs patients with
      gallstones without cancer, we associated exposure to aflatoxin (based on plasma
      level of AFB1-lysine) with gallbladder cancer. Gallbladder cancer does not appear
      associate with the R249S mutation in TP53. If aflatoxin is a cause of gallbladder
      cancer, it may have accounted for up to 20% of the gallbladder cancers in
      Shanghai, China, during the study period, and could account for an even higher
      proportion in high-risk areas. If our findings are verified, reducing aflatoxin
      exposure might reduce the incidence of gallbladder cancer.

PMID- 28428145
TI  - Prior treadmill exercise promotes resilience to vicarious trauma in rats.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is a serious psychological
      condition, which can develop both from physically experiencing and also from
      witnessing traumatic events. There is evidence that physical exercise can have a
      positive impact on the symptoms of PTSD. Relevant to this, in our previous pre
      clinical work, beneficial effects of treadmill exercise were reported on PTSD
      like behaviors in a social defeat paradigm, a rat model of direct physical
      trauma. However, the role of exercise on vicariously acquired PTSD-like phenotype
      was not examined. OBJECTIVE: In this study, we utilized a rodent PTSD model,
      which mimics both the physical as well as the witness experience of trauma, and
      examined the impact of moderate treadmill exercise in mitigating vicariously
      acquired PTSD-like behaviors in rats. METHODS: Our PTSD model is a modified
      social defeat paradigm, which involves aggressive encounters between a large Long
      Evans male rat (resident) and a smaller Sprague-Dawley male rat (intruder),
      resulting in intruder social defeat. The cage mate of the intruder is positioned
      to witness intruder defeat. Rats were grouped as control (CON), social defeat
      (SD), exercise (EX), trauma witness (TW), and exercise prior to trauma witness
      (EX-TW). After acclimatization for 7days, the exercised groups were subjected to
      a daily 30-min treadmill exercise regimen for 14days. On day 21, the SD group was
      exposed for 7days of social defeat, while the TW groups witnessed social defeat.
      On days 28-34, behavioral and cognitive tests including short-term (STM) and long
      term (LTM) memory function, anxiety- and depression-like behaviors were
      conducted. RESULTS: TW and SD rats demonstrated the highest levels of anxiety-
      and depression-like behaviors, while EX-TW rats did not exhibit anxiety- and
      depression-like behaviors. TW and SD rats showed no impairments in STM. However,
      TW and SD rats showed impairments in LTM, and exercise rescued LTM impairments in
      EX-TW rats. CONCLUSIONS: This study demonstrates that rats subjected to direct
      experience or witness of social defeat exhibited PTSD-like behaviors, while
      moderate treadmill exercise prevented trauma witness-induced behavioral
      impairments. These studies have important translational value suggesting that
      prior treadmill exercise might provide resilience to stressful stimuli and
      perhaps mitigate the witnessing effects of traumatic events.

PMID- 28428146
TI  - The correlation between mood states and functional connectivity within the
      default mode network can differentiate Internet gaming disorder from healthy
      controls.
AB  - The default-mode network (DMN) has been suggested to support a baseline state of
      brain activity. However, whether connectivity within the DMN is associated with
      mood states remains incompletely understood. The current study examined the
      correlation between mood state and the functional connectivity (FC) among DMN
      regions, and examined if the FC can differentiate Internet gaming disorder (IGD)
      from healthy controls (HC). Resting state data were collected within 108 college
      students (IGD,41; HC,67). Negative correlations were observed between measures
      of: (1) Depression and FCs among ventral DMN regions; (2) Anger and FCs among
      dorsal DMN regions; and, (3) Anger and Depression and FCs of both the ventral and
      dorsal DMN. The results suggest that negative mood states of Depression and Anger
      might reflect poorer, or might impair, FCs among DMN regions. In addition, the FC
      among DMNs could be useful indexes in differencing IGD from HC. Future studies
      should examine the extent to which the findings may extend to clinical
      populations and whether increased connectivity of DMN regions may represent a
      mechanism for reducing negative mood states.

PMID- 28428147
TI  - High genetic diversities between isolates of the fish parasite Cryptocaryon
      irritans (Ciliophora) suggest multiple cryptic species.
AB  - The ciliate protozoan Cryptocaryon irritans parasitizes marine fish and causes
      lethal white spot disease. Sporadic infections as well as large-scale outbreaks
      have been reported globally and the parasite's broad host range poses particular
      threat to the aquaculture and ornamental fish markets. In order to better
      understand C. irritans' population structure, we sequenced and compared
      mitochondrial cox-1, SSU rRNA, and ITS-1 sequences from 8 new isolates of C.
      irritans collected in China, Japan, and Taiwan. We detected two SSU rRNA
      haplotypes, which differ at three positions, separating the isolates into two
      main groups (I and II). Cox-1 sequences also support the division into two
      groups, and the cox-1 divergence between these two groups is unexpectedly high
      (9.28% for 1582 nucleotide positions). The divergence is much greater than that
      detected in Ichthyophthirius multifiliis, the ciliate protozoan causing
      freshwater white spot disease in fish, where intraspecies divergence on cox-1
      sequence is only 1.95%. ITS-1 sequences derived from these eight isolates and
      from all other C. irritans isolates (deposited in the GenBank) not only support
      the two groups, but further suggest the presence of a third group with even
      greater sequence divergence. Finally, a small Ka/Ks ratio estimated from cox-1
      sequences suggests that this gene in C. irritans remains under strong purifying
      selection. Taken together, the C. irritans species may consists of many
      subspecies and/or syngens. Further work is needed to determine if there is
      reproductive isolation between the groups we have defined.

PMID- 28428148
TI  - Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with
      Advanced Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: Tumor biopsies for detecting EGFR mutations in advanced NSCLC are
      invasive, costly, and not always feasible for patients with late-stage disease.
      The clinical utility of the cobas EGFR Mutation Test v2 (Roche Molecular Systems,
      Inc., Pleasanton, CA) with plasma samples from patients with NSCLC at disease
      progression after previous EGFR tyrosine kinase inhibitor therapy was
      investigated to determine eligibility for osimertinib treatment. METHODS: Matched
      tumor tissue and plasma samples from patients screened for the AURA extension and
      AURA2 phase II studies were tested for EGFR mutations by using tissue- and plasma
      based cobas EGFR mutation tests. Plasma test performance was assessed by using
      the cobas tissue test and a next-generation sequencing method (MiSeq [Illumina
      Inc., San Diego, CA]) as references. The objective response rate, measured by
      blinded independent central review, was assessed in patients receiving
      osimertinib with a plasma T790M mutation-positive status. RESULTS: During
      screening, 551 patients provided matched tumor tissue and plasma samples. Pooled
      analysis of the positive and negative percent agreements between the cobas plasma
      and tissue tests for detection of T790M mutation were 61% and 79%, respectively.
      Comparing cobas plasma test with next-generation sequencing demonstrated positive
      and negative percent agreements of 90% or higher. The objective response rate was
      64% (95% confidence interval: 57-70) in T790M mutation-positive patients by both
      cobas tissue and plasma tests (evaluable for response). CONCLUSIONS: The cobas
      plasma test detected the T790M mutation in 61% of tumor tissue T790M mutation
      positive patients. To mitigate the risk of false-negative plasma results,
      patients with a negative plasma result should undergo a tissue test where
      feasible.

PMID- 28428150
TI  - Satiety regulation in children with loss of control eating and attention
      deficit/hyperactivity disorder: A test meal study.
AB  - Children with loss of control (LOC) eating and attention-deficit/hyperactivity
      disorder (ADHD) are at risk for excessive weight gain. However, it is unclear
      whether or not these children show disturbances in hunger and satiety regulation.
      The goal was to examine the food intake and sense of LOC over eating as well as
      LOC eating-related characteristics during test meal in children with LOC eating
      and ADHD. Children aged 8-13 y with LOC eating (n = 33), ADHD (n = 32), and
      matched healthy controls (n = 33), consumed a test meal consisting of their
      chosen lunch food, with the instruction to eat until feeling full. Sense of LOC
      over eating, desire to eat, feelings of hunger, and liking of food were
      repeatedly assessed during test meal. Children with LOC eating and ADHD did not
      show a higher food intake at maximum satiety compared to control children. Sense
      of LOC over eating was significantly higher in children with LOC eating compared
      to children with ADHD and matched controls. Secondary analyses revealed that
      children with LOC eating ate marginally faster than control children. Both
      children with LOC eating and ADHD reported greater desire to eat, feelings of
      hunger, and liking of food during test meal than control children. Even though
      the results did not reveal statistical evidence to support the assumption of a
      disturbed food intake in children with LOC eating and ADHD, LOC eating related
      characteristics were significantly higher in these children compared to the
      control children. Sense of LOC over eating was confirmed as a specific
      characteristic of LOC eating. The examination of behavioral indicators of hunger
      and satiety dysregulation should be complemented with physiological indicators in
      future research.

PMID- 28428149
TI  - Local Control and Toxicity of Adaptive Radiotherapy Using Weekly CT Imaging:
      Results from the LARTIA Trial in Stage III NSCLC.
AB  - INTRODUCTION: Anatomical change of tumor during radiotherapy contributes to
      target missing. However, in the case of tumor shrinkage, adaptation of volume
      could result in an increased incidence of recurrence in the area of target
      reduction. This study aims to investigate the incidence of failure of the
      adaptive approach and, in particular, the risk for local recurrence in the area
      excluded after replanning. METHODS: In this prospective study, patients with
      locally advanced NSCLC treated with concomitant chemoradiation underwent weekly
      chest computed tomography simulation during treatment. In the case of tumor
      shrinkage, a new tumor volume was delineated and a new treatment plan outlined
      (replanning). Toxicity was evaluated with the Radiation Therapy Oncology
      Group/European Organization for Research and Treatment of Cancer scale. Patterns
      of failures were classified as in field (dimensional and/or metabolic progression
      within the replanning planning target volume [PTV]), marginal (recurrence in
      initial the PTV excluded from the replanning PTV), and out of field (recurrence
      outside the initial PTV). RESULTS: Replanning was outlined in 50 patients
      selected from a total of 217 patients subjected to weekly simulation computed
      tomography in our center from 2012 to 2014. With a median follow-up of 20.5
      months, acute grade 3 or higher pulmonary and esophageal toxicity were reported
      in 2% and 4% of cases and late toxicity in 4% and 2%, respectively. Marginal
      relapse was recorded in 6% of patients, and 20% and 4% of patients experienced in
      field and out-of-field local failure, respectively. CONCLUSIONS: The reduced
      toxicity and the documented low rate of marginal failures make the adaptive
      approach a modern option for future randomized studies. The best scenario to
      confirm its application is probably in neoadjuvant chemoradiation trials.

PMID- 28428151
TI  - Impact of front-of-pack nutrition information and label design on children's
      choice of two snack foods: Comparison of warnings and the traffic-light system.
AB  - Research on the relative influence of package features on children's perception
      of food products is still necessary to aid policy design and development. The aim
      of the present work was to evaluate the relative influence of two front-of-pack
      (FOP) nutrition labelling schemes, the traffic light system and Chilean warning
      system, and label design on children's choice of two popular snack foods in
      Uruguay, wafer cookies and orange juice. A total of 442 children in grades 4 to 6
      from 12 primary schools in Montevideo (Uruguay) participated in the study. They
      were asked to complete a choice-conjoint task with wafer cookies and orange juice
      labels, varying in label design and the inclusion of FOP nutrition information.
      Half of the children completed the task with labels featuring the traffic-light
      system (n = 217) and the other half with labels featuring the Chilean warning
      system (n = 225). Children's choices of wafer cookies and juice labels was
      significantly influenced by both label design and FOP nutritional labels. The
      relative impact of FOP nutritional labelling on children's choices was higher for
      the warning system compared to the traffic-light system. Results from the present
      work stress the need to regulate the design of packages and the inclusion of
      nutrient claims, and provide preliminary evidence of the potential of warnings to
      discourage children's choice of unhealthful products.

PMID- 28428152
TI  - Convenience food with environmentally-sustainable attributes: A consumer
      perspective.
AB  - The use of chemicals in agriculture poses risks on both human health and the
      environment. Regulatory measures, both mandatory and voluntary, have been
      introduced to promote a reduction in the use of pesticides. The proliferation of
      such standards is related to the gradual shift of consumer preferences towards
      food with reduced negative health and environmental impacts. Beside consumer
      demand for sustainable food products, convenience food is also assuming an
      increasingly important role in developed countries. Among such products,
      minimally-processed vegetables are showing a growing positive trend, but their
      production has also negative effects on the environment. The goal of this study
      is to investigate the interaction between environmentally-friendly and healthy
      convenience food, and to investigate the determinants behind the purchase of
      healthy convenience food products with environmentally-sustainable attributes,
      focusing on minimally-processed vegetables labelled with voluntary standards
      related to integrated agriculture. To do so, we started from the Theory of
      Planned Behaviour and tested the efficacy of an extended model by considering
      also other variables which were found to affect significantly food choices. Data
      were collected by means of face-to-face interviews with 550 consumers in charge
      of grocery shopping in the metropolitan area of Milan, in northern Italy.
      Structural equation modelling was performed to analyse the relative importance of
      the constructs on consumer behaviour. Results confirm the relations of Ajzen's
      theory and reveal positive relations with consumer food shopping habits, food
      related environmental behaviour, gender, income and knowledge. A negative
      relation with agricultural practices concern also emerges, highlighting that the
      most concerned consumers may prefer other more stringent environmental
      certifications.

PMID- 28428153
TI  - Development of polyol-responsive antibody mimetics for single-step protein
      purification.
AB  - The purification of functional proteins is a critical pre-requisite for many
      experimental assays. Immunoaffinity chromatography, one of the fastest and most
      efficient purification procedures available, is often limited by elution
      conditions that disrupt structure and destroy enzymatic activity. To address this
      limitation, we developed polyol-responsive antibody mimetics, termed nanoCLAMPs,
      based on a 16 kDa carbohydrate binding module domain from Clostridium perfringens
      hyaluronidase. nanoCLAMPs bind targets with nanomolar affinity and high
      selectivity yet release their targets when exposed to a neutral polyol-containing
      buffer, a composition others have shown to preserve quaternary structure and
      enzymatic activity. We screened a phage display library for nanoCLAMPs
      recognizing several target proteins, produced affinity resins with the resulting
      nanoCLAMPs, and successfully purified functional target proteins by single-step
      affinity chromatography and polyol elution. To our knowledge, nanoCLAMPs
      constitute the first antibody mimetics demonstrated to be polyol-responsive.

PMID- 28428154
TI  - Bias in medicine in the context of the film Aligarh.
AB  - In today's world, I feel another sin needs to be added to the list of the seven
      deadly sins, viz the sin of intolerance. We hear this term on the news every
      other day and see society display this attitude more often than not. While the
      movie Aligarh raised myriad social issues, as a medical student, I would like to
      speak of one in particular - the influence of stigma on healthcare.

PMID- 28428155
TI  - Using Persuasive Technology to Increase Physical Activity in People With Chronic
      Obstructive Pulmonary Disease by Encouraging Regular Walking: A Mixed-Methods
      Study Exploring Opinions and Preferences.
AB  - BACKGROUND: People with chronic obstructive pulmonary disease (PwCOPD) often
      experience breathlessness and fatigue, making physical activity challenging.
      Although many persuasive technologies (such as mobile phone apps) have been
      designed to support physical activity among members of the general population,
      current technologies aimed at PwCOPD are underdeveloped and only use a limited
      range of persuasive technology design principles. OBJECTIVE: The aim of this
      study was to explore how acceptable different persuasive technology design
      principles were considered to be in supporting and encouraging physical activity
      among PwCOPD. METHODS: Three prototypes for mobile apps using different
      persuasive technology design principles as defined by the persuasive systems
      design (PSD) model-namely, dialogue support, primary task support, and social
      support-were developed. Opinions of these prototypes were explored through 28
      interviews with PwCOPD, carers, and the health care professionals (HCPs) involved
      in their care and questionnaires completed by 87 PwCOPD. Participants also ranked
      how likely individual techniques (eg, competition) would be to convince them to
      use a technology designed to support physical activity. Data were analyzed using
      framework analysis, Friedman tests, and Wilcoxon signed rank tests and a
      convergent mixed methods design was used to integrate findings. RESULTS: The
      prototypes for mobile apps were received positively by participants. The
      prototype that used a dialogue support approach was identified as the most likely
      to be used or recommended by those interviewed, and was perceived as more
      persuasive than both of the other prototypes (Z=-3.06, P=.002; Z=-5.50, P<.001)
      by those who completed the questionnaire. PwCOPD identified dialogue support and
      primary task support techniques as more likely to convince them to use a
      technology than social support techniques (Z=-5.00, P<.001; Z=-4.92, P<.001,
      respectively). Opinions of social support techniques such as competition and
      collaboration were divided. CONCLUSIONS: Dialogue support and primary task
      support approaches are considered to be both acceptable and likely to be
      persuasive by PwCOPD, carers, and HCPs. In the future, these approaches should be
      considered when designing apps to encourage physical activity by PwCOPD.

PMID- 28428156
TI  - User Interest in Digital Health Technologies to Encourage Physical Activity:
      Results of a Survey in Students and Staff of a German University.
AB  - BACKGROUND: Although the benefits for health of physical activity (PA) are well
      documented, the majority of the population is unable to implement present
      recommendations into daily routine. Mobile health (mHealth) apps could help
      increase the level of PA. However, this is contingent on the interest of
      potential users. OBJECTIVE: The aim of this study was the explorative, nuanced
      determination of the interest in mHealth apps with respect to PA among students
      and staff of a university. METHODS: We conducted a Web-based survey from June to
      July 2015 in which students and employees from the University of Potsdam were
      asked about their activity level, interest in mHealth fitness apps, chronic
      diseases, and sociodemographic parameters. RESULTS: A total of 1217 students
      (67.30%, 819/1217; female; 26.0 years [SD 4.9]) and 485 employees (67.5%,
      327/485; female; 42.7 years [SD 11.7]) participated in the survey. The
      recommendation for PA (3 times per week) was not met by 70.1% (340/485) of
      employees and 52.67% (641/1217) of students. Within these groups, 53.2% (341/641
      students) and 44.2% (150/340 employees)-independent of age, sex, body mass index
      (BMI), and level of education or professional qualification-indicated an interest
      in mHealth fitness apps. CONCLUSIONS: Even in a younger, highly educated
      population, the majority of respondents reported an insufficient level of PA.
      About half of them indicated their interest in training support. This suggests
      that the use of personalized mobile fitness apps may become increasingly
      significant for a positive change of lifestyle.

PMID- 28428157
TI  - Texting and Mobile Phone App Interventions for Improving Adherence to Preventive
      Behavior in Adolescents: A Systematic Review.
AB  - BACKGROUND: Many preventable behaviors contribute to adolescent mortality and
      morbidity. Non-adherence to preventive measures represents a challenge and has
      been associated with worse health outcomes in this population. The widespread use
      of electronic communication technologies by adolescents, particularly the use of
      text messaging (short message service, SMS) and mobile phones, presents new
      opportunities to intervene on risk and preventive risk behavior, but little is
      known about their efficacy. OBJECTIVE: This study aimed to systematically
      evaluate evidence for the efficacy of text messaging and mobile phone app
      interventions to improve adherence to preventive behavior among adolescents and
      describe intervention approaches to inform intervention development. METHODS:
      This review covers literature published between 1995 and 2015. Searches included
      PubMed, Embase, CENTRAL, PsycINFO, CINAHL, INSPEC, Web of Science, Google
      Scholar, and additional databases. The search strategy sought articles on text
      messaging and mobile phone apps combined with adherence or compliance, and
      adolescents and youth. An additional hand search of related themes in the Journal
      of Medical Internet Research was also conducted. Two reviewers independently
      screened titles and abstracts, assessed full-text articles, and extracted data
      from articles that met inclusion criteria. Included studies reflect original
      research-experimental or preexperimental designs with text messaging or mobile
      phone app interventions-targeting adherence to preventive behavior among
      adolescents (12-24 years old). The preferred reporting items of systematic
      reviews and meta-analyses (PRISMA) guidelines were followed for reporting
      results, and findings were critically appraised against the Oxford Centre for
      Evidence-based Medicine criteria. RESULTS: Of 1454 records, 19 met inclusion
      criteria, including text messaging (n=15) and mobile phone apps (n=4). Studies
      targeted clinic attendance, contraceptive use, oral health, physical activity and
      weight management, sun protection, human papillomavirus (HPV) vaccination,
      smoking cessation, and sexual health. Most studies were performed in the United
      States (47%, 9/19), included younger adolescents (63%, 12/19), and had sample
      size <100 (63%, 12/19). Although most studies were randomized controlled trials
      (RCTs; 58%, 11/19), only 5 followed an intent-to-treat analysis. Only 6 of 19
      studies (32%) incorporated a theoretical framework in their design. Most studies
      reported good feasibility with high acceptability and satisfaction. About half of
      the included studies (42%, 8/19) demonstrated significant improvement in
      preventive behavior with moderate standardized mean differences. As early efforts
      in this field to establish feasibility and initial efficacy, most studies were
      low to moderate in quality. Studies varied in sample size and methods of
      preventive behavior adherence or outcome assessment, which prohibited performing
      a meta-analysis. CONCLUSIONS: Despite the promising feasibility and acceptability
      of text messaging and mobile phone apps in improving preventive behavior among
      adolescents, overall findings were modest in terms of efficacy. Further research
      evaluating the efficacy, effectiveness, and cost-effectiveness of these
      intervention approaches in promoting preventive behavior among adolescents is
      needed.

PMID- 28428158
TI  - Mobile Application to Promote Adherence to Oral Chemotherapy and Symptom
      Management: A Protocol for Design and Development.
AB  - BACKGROUND: Oral chemotherapy is increasingly used in place of traditional
      intravenous chemotherapy to treat patients with cancer. While oral chemotherapy
      includes benefits such as ease of administration, convenience, and minimization
      of invasive infusions, patients receive less oversight, support, and symptom
      monitoring from clinicians. Additionally, adherence is a well-documented
      challenge for patients with cancer prescribed oral chemotherapy regimens. With
      the ever-growing presence of smartphones and potential for efficacious behavioral
      intervention technology, we created a mobile health intervention for medication
      and symptom management. OBJECTIVE: The objective of this study was to develop and
      evaluate the usability and acceptability of a smartphone app to support adherence
      to oral chemotherapy and symptom management in patients with cancer. METHODS: We
      used a 5-step development model to create a comprehensive mobile app with
      theoretically informed content. The research and technical development team
      worked together to develop and iteratively test the app. In addition to the
      research team, key stakeholders including patients and family members, oncology
      clinicians, health care representatives, and practice administrators contributed
      to the content refinement of the intervention. Patient and family members also
      participated in alpha and beta testing of the final prototype to assess usability
      and acceptability before we began the randomized controlled trial. RESULTS: We
      incorporated app components based on the stakeholder feedback we received in
      focus groups and alpha and beta testing. App components included medication
      reminders, self-reporting of medication adherence and symptoms, an education
      library including nutritional information, Fitbit integration, social networking
      resources, and individually tailored symptom management feedback. We are
      conducting a randomized controlled trial to determine the effectiveness of the
      app in improving adherence to oral chemotherapy, quality of life, and burden of
      symptoms and side effects. At every stage in this trial, we are engaging
      stakeholders to solicit feedback on our progress and next steps. CONCLUSIONS: To
      our knowledge, we are the first to describe the development of an app designed
      for people taking oral chemotherapy. The app addresses many concerns with oral
      chemotherapy, such as medication adherence and symptom management. Soliciting
      feedback from stakeholders with broad perspectives and expertise ensured that the
      app was acceptable and potentially beneficial for patients, caregivers, and
      clinicians. In our development process, we instantiated 7 of the 8 best practices
      proposed in a recent review of mobile health app development. Our process
      demonstrated the importance of effective communication between research groups
      and technical teams, as well as meticulous planning of technical specifications
      before development begins. Future efforts should consider incorporating other
      proven strategies in software, such as gamification, to bolster the impact of
      mobile health apps. Forthcoming results from our randomized controlled trial will
      provide key data on the effectiveness of this app in improving medication
      adherence and symptom management. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02157519; https://clinicaltrials.gov/ct2/show/NCT02157519 (Archived by WebCite
      at http://www.webcitation.org/6prj3xfKA).

PMID- 28428159
TI  - Development of a Culturally Tailored Text Message Maternal Health Program:
      TextMATCH.
AB  - BACKGROUND: Mobile phones are increasingly being used to deliver health
      information and health services globally. Mobile health (mHealth) interventions
      may be well-suited for minority groups with greater barriers to accessing
      traditional health services. However, little has been written about the process
      of culturally adapting interventions for multiple ethnic and cultural minorities
      within a population. OBJECTIVE: This study describes the process of developing a
      culturally tailored text message-based maternal health program (TextMATCH: Text
      for MATernal and Child Health) for Maori, Pacific, Asian, and South Asian
      families living in New Zealand. We report on engagement and acceptability of the
      TextMATCH program. METHODS: Program data was examined to describe engagement with
      the program 18 months after implementation. Telephone interviews were conducted
      with a sample of participants who consented to provide feedback on acceptability
      and relevance of the program. RESULTS: A total of 1404 participants enrolled in
      TextMATCH over 18 months, with 18.52% (260) actively opting out at some point
      (after 0 to 17 months of messages). It was found that 356 (70.9%) of the 502
      eligible participants actively switched from the initial pregnancy program to the
      baby program after delivery. Phone interviews were conducted with 29 participants
      including 6 who had withdrawn (duration of program from 3 to 16 months). Only 2
      participants reported that the program was not useful, with the remainder rating
      the usefulness of messages positively (average 4.24 out of 5). All participants
      stated that the messages were relevant, culturally appropriate, and easy to
      understand. Most were happy with the specific advice and the language options
      provided. CONCLUSIONS: We have demonstrated the importance of an intensive
      approach to the development of a culturally adapted and tailored mHealth program
      for multiple different cultural minority groups within our population.

PMID- 28428160
TI  - Simulated Conversations With Virtual Humans to Improve Patient-Provider
      Communication and Reduce Unnecessary Prescriptions for Antibiotics: A Repeated
      Measure Pilot Study.
AB  - BACKGROUND: Despite clear evidence that antibiotics do not cure viral infections,
      the problem of unnecessary prescribing of antibiotics in ambulatory care
      persists, and in some cases, prescribing patterns have increased. The overuse of
      antibiotics for treating viral infections has created numerous economic and
      clinical consequences including increased medical costs due to unnecessary
      hospitalizations, antibiotic resistance, disruption of gut bacteria, and obesity.
      Recent research has underscored the importance of collaborative patient-provider
      communication as a means to reduce the high rates of unnecessary prescriptions
      for antibiotics. However, most patients and providers do not feel prepared to
      engage in such challenging conversations. OBJECTIVES: The aim of this pilot study
      was to assess the ability of a brief 15-min simulated role-play conversation with
      virtual humans to serve as a preliminary step to help health care providers and
      patients practice, and learn how to engage in effective conversations about
      antibiotics overuse. METHODS: A total of 69 participants (35 providers and 34
      patients) completed the simulation once in one sitting. A pre-post repeated
      measures design was used to assess changes in patients' and providers' self
      reported communication behaviors, activation, and preparedness, intention, and
      confidence to effectively communicate in the patient-provider encounter. Changes
      in patients' knowledge and beliefs regarding antibiotic use were also evaluated.
      RESULTS: Patients experienced a short-term positive improvement in beliefs about
      appropriate antibiotic use for infection (F1,30=14.10, P=.001). Knowledge scores
      regarding the correct uses of antibiotics improved immediately postsimulation,
      but decreased at the 1-month follow-up (F1,30=31.16, P<.001). There was no change
      in patient activation and shared decision-making (SDM) scores in the total sample
      of patients (P>.10) Patients with lower levels of activation exhibited positive,
      short-term benefits in increased intent and confidence to discuss their needs and
      ask questions in the clinic visit, positive attitudes regarding participation in
      SDM with their provider, and accurate beliefs about the use of antibiotics
      (P<.10). The results also suggest small immediate gains in providers' attitudes
      about SDM (mean change 0.20; F1,33= 8.03, P=.01). CONCLUSIONS: This pilot study
      provided preliminary evidence on the efficacy of the use of simulated
      conversations with virtual humans as a tool to improve patient-provider
      communication (ie, through increasing patient confidence to actively participate
      in the visit and physician attitudes about SDM) for engaging in conversations
      about antibiotic use. Future research should explore if repeated opportunities to
      use the 15-min simulation as well as providing users with several different
      conversations to practice with would result in sustained improvements in
      antibiotics beliefs and knowledge and communication behaviors over time. The
      results of this pilot study offered several opportunities to improve on the
      simulation in order to bolster communication skills and knowledge retention.

PMID- 28428161
TI  - Toward Game-Based Digital Mental Health Interventions: Player Habits and
      Preferences.
AB  - BACKGROUND: Designers of digital interventions for mental health often leverage
      interactions from games because the intrinsic motivation that results from game
      based interventions may increase participation and translate into improved
      treatment efficacy. However, there are outstanding questions about the
      suitability (eg, are desktop or mobile interventions more appropriate?) and
      intervention potential (eg, do people with depression activate enough to play?)
      of games for mental health. OBJECTIVE: In this paper, we aimed to describe the
      presently unknown relationship between gaming activity and indicators of well
      being so that designers make informed choices when designing game-based
      interventions for mental health. METHODS: We gathered validated scales of well
      being (Beck's Depression Inventory [BDI-II], Patient Health Questionnaire [PHQ
      9], trait anxiety [TA], and basic psychological needs satisfaction [BPNS]), play
      importance (control over game behavior: control; gamer identity: identity), and
      play behavior (play frequency, platform preferences, and genre preferences) in a
      Web-based survey (N=491). RESULTS: The majority of our participants played games
      a few times a week (45.3%, 222/490) or daily (34.3%, 168/490). In terms of
      depression, play frequency was associated with PHQ-9 (P=.003); PHQ-9 scores were
      higher for those who played daily than for those who played a few times a week or
      less. Similarly, for BDI-II (P=.01), scores were higher for those who played
      daily than for those who played once a week or less. Genre preferences were not
      associated with PHQ-9 (P=.32) or BDI-II (P=.68); however, platform preference
      (ie, mobile, desktop, or console) was associated with PHQ-9 (P=.04); desktop-only
      players had higher PHQ-9 scores than those who used all platforms. Platform
      preference was not associated with BDI-II (P=.18). In terms of anxiety, TA was
      not associated with frequency (P=.23), platform preference (P=.07), or genre
      preference (P=.99). In terms of needs satisfaction, BPNS was not associated with
      frequency (P=.25) or genre preference (P=.53), but it was associated with
      platform preference (P=.01); desktop-only players had lower needs satisfaction
      than those who used all platforms. As expected, play frequency was associated
      with identity (P<.001) and control (P<.001); those who played more had identified
      more as a gamer and had less control over their gameplay. Genre preference was
      associated with identity (P<.001) and control (P<.001); those who played most
      common genres had higher control over their play and identified most as gamers.
      Platform preference was not associated with control (P=.80), but was with
      identity (P=.001); those who played on all devices identified more as a gamer
      than those who played on mobiles or consoles only. CONCLUSIONS: Our results
      suggest that games are a suitable approach for mental health interventions as
      they are played broadly by people across a range of indicators of mental health.
      We further unpack the platform preferences and genre preferences of players with
      varying levels of well-being.

PMID- 28428162
TI  - The Use of Intervention Mapping to Develop a Tailored Web-Based Intervention,
      Condom-HIM.
AB  - BACKGROUND: Many HIV (human immunodeficiency virus) prevention interventions are
      currently being implemented and evaluated, with little information published on
      their development. A framework highlighting the method of development of an
      intervention can be used by others wanting to replicate interventions or develop
      similar interventions to suit other contexts and settings. It provides
      researchers with a comprehensive development process of the intervention.
      OBJECTIVE: The objective of this paper was to describe how a systematic approach,
      intervention mapping, was used to develop a tailored Web-based intervention to
      increase condom use among HIV-positive men who have sex with men. METHODS: The
      intervention was developed in consultation with a multidisciplinary team composed
      of academic researchers, community members, Web designers, and the target
      population. Intervention mapping involved a systematic process of 6 steps: (1)
      needs assessment; (2) identification of proximal intervention objectives; (3)
      selection of theory-based intervention methods and practical strategies; (4)
      development of intervention components and materials; (5) adoption,
      implementation, and maintenance; and (6) evaluation planning. RESULTS: The
      application of intervention mapping resulted in the development of a tailored Web
      based intervention for HIV-positive men who have sex with men, called Condom-HIM.
      CONCLUSIONS: Using intervention mapping as a systematic process to develop
      interventions is a feasible approach that specifically integrates the use of
      theory and empirical findings. Outlining the process used to develop a particular
      intervention provides clarification on the conceptual use of experimental
      interventions in addition to potentially identifying reasons for intervention
      failures.

PMID- 28428163
TI  - Public Response to Scientific Misconduct: Assessing Changes in Public Sentiment
      Toward the Stimulus-Triggered Acquisition of Pluripotency (STAP) Cell Case via
      Twitter.
AB  - BACKGROUND: In this age of social media, any news-good or bad-has the potential
      to spread in unpredictable ways. Changes in public sentiment have the potential
      to either drive or limit investment in publicly funded activities, such as
      scientific research. As a result, understanding the ways in which reported cases
      of scientific misconduct shape public sentiment is becoming increasingly
      essential-for researchers and institutions, as well as for policy makers and
      funders. In this study, we thus set out to assess and define the patterns
      according to which public sentiment may change in response to reported cases of
      scientific misconduct. This study focuses on the public response to the events
      involved in a recent case of major scientific misconduct that occurred in 2014 in
      Japan-stimulus-triggered acquisition of pluripotency (STAP) cell case.
      OBJECTIVES: The aims of this study were to determine (1) the patterns according
      to which public sentiment changes in response to scientific misconduct; (2)
      whether such measures vary significantly, coincident with major timeline events;
      and (3) whether the changes observed mirror the response patterns reported in the
      literature with respect to other classes of events, such as entertainment news
      and disaster reports. METHODS: The recent STAP cell scandal is used as a test
      case. Changes in the volume and polarity of discussion were assessed using a
      sampling of case-related Twitter data, published between January 28, 2014 and
      March 15, 2015. Rapidminer was used for text processing and the popular bag-of
      words algorithm, SentiWordNet, was used in Rapidminer to calculate sentiment for
      each sample Tweet. Relative volume and sentiment was then assessed overall, month
      to-month, and with respect to individual entities. RESULTS: Despite the
      ostensibly negative subject, average sentiment over the observed period tended to
      be neutral (-0.04); however, a notable downward trend (y=-0.01 x +0.09; R 2=.45)
      was observed month-to-month. Notably polarized tweets accounted for less than one
      third of sampled discussion: 17.49% (1656/9467) negative and 12.59% positive
      (1192/9467). Significant polarization was found in only 4 out of the 15 months
      covered, with significant variation month-to-month (P<.001). Significant
      increases in polarization tended to coincide with increased discussion volume
      surrounding major events (P<.001). CONCLUSIONS: These results suggest that public
      opinion toward scientific research may be subject to the same sensationalist
      dynamics driving public opinion in other, consumer-oriented topics. The patterns
      in public response observed here, with respect to the STAP cell case, were found
      to be consistent with those observed in the literature with respect to other
      classes of news-worthy events on Twitter. Discussion was found to become strongly
      polarized only during times of increased public attention, and such increases
      tended to be driven primarily by negative reporting and reactionary commentary.

PMID- 28428164
TI  - Zika in Twitter: Temporal Variations of Locations, Actors, and Concepts.
AB  - BACKGROUND: The recent Zika outbreak witnessed the disease evolving from a
      regional health concern to a global epidemic. During this process, different
      communities across the globe became involved in Twitter, discussing the disease
      and key issues associated with it. This paper presents a study of this discussion
      in Twitter, at the nexus of location, actors, and concepts. OBJECTIVE: Our
      objective in this study was to demonstrate the significance of 3 types of events:
      location related, actor related, and concept related, for understanding how a
      public health emergency of international concern plays out in social media, and
      Twitter in particular. Accordingly, the study contributes to research efforts
      toward gaining insights on the mechanisms that drive participation,
      contributions, and interaction in this social media platform during a disease
      outbreak. METHODS: We collected 6,249,626 tweets referring to the Zika outbreak
      over a period of 12 weeks early in the outbreak (December 2015 through March
      2016). We analyzed this data corpus in terms of its geographical footprint, the
      actors participating in the discourse, and emerging concepts associated with the
      issue. Data were visualized and evaluated with spatiotemporal and network
      analysis tools to capture the evolution of interest on the topic and to reveal
      connections between locations, actors, and concepts in the form of interaction
      networks. RESULTS: The spatiotemporal analysis of Twitter contributions reflects
      the spread of interest in Zika from its original hotspot in South America to
      North America and then across the globe. The Centers for Disease Control and
      World Health Organization had a prominent presence in social media discussions.
      Tweets about pregnancy and abortion increased as more information about this
      emerging infectious disease was presented to the public and public figures became
      involved in this. CONCLUSIONS: The results of this study show the utility of
      analyzing temporal variations in the analytic triad of locations, actors, and
      concepts. This contributes to advancing our understanding of social media
      discourse during a public health emergency of international concern.

PMID- 28428165
TI  - A Framework for the Study of Complex mHealth Interventions in Diverse Cultural
      Settings.
AB  - BACKGROUND: To facilitate decision-making capacity between options of care under
      real-life service conditions, clinical trials must be pragmatic to evaluate
      mobile health (mHealth) interventions under the variable conditions of health
      care settings with a wide range of participants. The mHealth interventions
      require changes in the behavior of patients and providers, creating considerable
      complexity and ambiguity related to causal chains. Process evaluations of the
      implementation are necessary to shed light on the range of unanticipated effects
      an intervention may have, what the active ingredients in everyday practice are,
      how they exert their effect, and how these may vary among recipients or between
      sites. OBJECTIVE: Building on the CONSORT-EHEALTH (Consolidated Standards of
      Reporting Trials of Electronic and Mobile HEalth Applications and onLine
      TeleHealth) statement and participatory evaluation theory, we present a framework
      for the process evaluations for mHealth interventions in multiple cultural
      settings. We also describe the application of this evaluation framework to the
      implementation of DREAM-GLOBAL (Diagnosing hypertension-Engaging Action and
      Management in Getting Lower BP in Indigenous and LMIC [low- and middle-income
      countries]), a pragmatic randomized controlled trial (RCT), and mHealth
      intervention designed to improve hypertension management in low-resource
      environments. We describe the evaluation questions and the data collection
      processes developed by us. METHODS: Our literature review revealed that there is
      a significant knowledge gap related to the development of a process evaluation
      framework for mHealth interventions. We used community-based participatory
      research (CBPR) methods and formative research data to develop a process
      evaluation framework nested within a pragmatic RCT. RESULTS: Four human
      organizational levels of participants impacted by the mHealth intervention were
      identified that included patients, providers, community and organizations actors,
      and health systems and settings. These four levels represent evaluation domains
      and became the core focus of the evaluation. In addition, primary implementation
      themes to explore in each of the domains were identified as follows: (1) the
      major active components of the intervention, (2) technology of the intervention,
      (3) cultural congruence, (4) task shifting, and (5) unintended consequences.
      Using the four organizational domains and their interaction with primary
      implementation themes, we developed detailed evaluation research questions and
      identified the data or information sources to best answer our questions.
      CONCLUSIONS: Using DREAM-GLOBAL to illustrate our approach, we succeeded in
      developing an uncomplicated process evaluation framework for mHealth
      interventions that provide key information to stakeholders, which can optimize
      implementation of a pragmatic trial as well as inform scale up. The human
      organizational level domains used to focus the primary implementation themes in
      the DREAM-GLOBAL process evaluation framework are sufficiently supported in our
      research, and the literature and can serve as a valuable tool for other mHealth
      process evaluations. TRIAL REGISTRATION: ClinicalTrials.gov NCT02111226;
      https://clinicaltrials.gov/ct2/show/NCT02111226 (Archived by WebCite at
      http://www.webcitation.org/6oxfHXege).

PMID- 28428166
TI  - Vascular Cognitive Impairment in a Memory Clinic Population: Rationale and Design
      of the "Utrecht-Amsterdam Clinical Features and Prognosis in Vascular Cognitive
      Impairment" (TRACE-VCI) Study.
AB  - BACKGROUND: Vascular Cognitive Impairment (VCI) refers to cognitive dysfunction
      due to vascular brain injury, as a single cause or in combination with other,
      often neurodegenerative, etiologies. VCI is a broad construct that captures a
      heterogeneous patient population both in terms of cognitive and noncognitive
      symptoms and in terms of etiology and prognosis. This provides a challenge when
      applying this construct in clinical practice. OBJECTIVE: This paper presents the
      rationale and design of the TRACE-VCI study, which investigates the clinical
      features and prognosis of VCI in a memory clinic setting. METHODS: The TRACE-VCI
      project is an observational, prospective cohort study of 861 consecutive memory
      clinic patients with possible VCI. Between 2009 and 2013, patients were recruited
      through the Amsterdam Dementia Cohort of the VU University Medical Centre (VUMC)
      (N=665) and the outpatient memory clinic and VCI cohort of the University Medical
      Centre Utrecht (UMCU) (N=196). We included all patients attending the clinics
      with magnetic resonance imaging (MRI) evidence of vascular brain injury. Patients
      with a primary etiology other than vascular brain injury or neurodegeneration
      were excluded. Patients underwent an extensive 1-day memory clinic evaluation
      including an interview, physical and neurological examination, assessment of
      biomarkers (including those for Alzheimer-type pathologies), extensive
      neuropsychological testing, and an MRI scan of the brain. For prognostic
      analyses, the composite primary outcome measure was defined as accelerated
      cognitive decline (change of clinical dementia rating >=1 or
      institutionalization) or (recurrent) major vascular events or death over the
      course of 2 years. RESULTS: The mean age at baseline was 67.7 (SD 8.5) years and
      46.3% of patients (399/861) were female. At baseline, the median Clinical
      Dementia Rating was 0.5 (interquartile range [IQR] 0.5-1.0) and the median Mini
      Mental State Examination score was 25 (IQR 22-28). The clinical diagnosis at
      baseline was dementia in 52.4% of patients (451/861), mild cognitive impairment
      in 24.6% (212/861), and no objective cognitive impairment in the remaining 23.0%
      (198/861). CONCLUSIONS: The TRACE-VCI study represents a large cohort of well
      characterized patients with VCI in a memory clinic setting. Data processing and
      collection for follow-up are currently being completed. The TRACE-VCI study will
      provide insight into the clinical features of memory clinic patients that meet
      VCI criteria and establish key prognostic factors for further cognitive decline
      and (recurrent) major vascular events.

PMID- 28428167
TI  - Developing a Patient-Centered mHealth App: A Tool for Adolescents With Type 1
      Diabetes and Their Parents.
AB  - BACKGROUND: Type 1 diabetes (T1D) afflicts approximately 154,000 people under 20
      years of age. Three-quarters of adolescents are not achieving glycosylated
      hemoglobin (HbA1c) targets, which leads to negative health outcomes. Mobile
      health (mHealth), the use of technology in health, has been used successfully to
      improve health in many chronic conditions, including diabetes. OBJECTIVE: The
      purpose of this study was to use patient-centered research methods to inform and
      improve the design and functionality of our T1D app, MyT1DHero, and to provide
      insight for others who are designing a health app for adolescents and parents.
      METHODS: This study included data from focus groups with participants recruited
      from the Juvenile Diabetes Research Foundation (JDRF) southeast Michigan's family
      network. All data collected during the sessions were audio-recorded, transcribed,
      and coded. RESULTS: Four key themes were identified: (1) diabetes is
      unpredictable, (2) negative and frustrated communication, (3) motivations to use
      an app, and (4) feedback specific to our app. CONCLUSIONS: A patient-centered
      approach was used to assist in the development of an app for adolescents with
      T1D. Participants were satisfied with overall app design; customization,
      interactivity, and tangible rewards were identified as being necessary for
      continued use. Participants believed the app would help improve the communication
      between parents and adolescents. Many apps developed in the health context have
      not used a patient-centered design method or have seen vast improvements in
      health. This paper offers suggestions to others seeking to develop apps for
      adolescents and their parents.

PMID- 28428168
TI  - Testing the Feasibility and Usability of a Novel Smartphone-Based Self-Management
      Support System for Dialysis Patients: A Pilot Study.
AB  - BACKGROUND: Diet and fluid restrictions that need continuous self-management are
      among the most difficult aspects of dialysis treatment. Smartphone applications
      may be useful for supporting self-management. OBJECTIVE: Our objective is to
      investigate the feasibility and usability of a novel smartphone-based self
      management support system for dialysis patients. METHODS: We developed the Self
      Management and Recording System for Dialysis (SMART-D), which supports self
      monitoring of three mortality-related factors that can be modified by lifestyle:
      interdialytic weight gain and predialysis serum potassium and phosphorus
      concentrations. Data is displayed graphically, with all data evaluated
      automatically to determine whether they achieve the values suggested by the
      Japanese Society for Dialysis Therapy guidelines. In a pilot study, 9 dialysis
      patients used SMART-D system for 2 weeks. A total of 7 of them completed
      questionnaires rating their assessment of SMART-D's usability and their
      satisfaction with the system. In addition, the Kidney Disease Quality of Life
      scale was compared before and after the study period. RESULTS: All 9 participants
      were able to use SMART-D with no major problems. Completion rates for body
      weight, pre- and postdialysis weight, and serum potassium and phosphorus
      concentrations were, respectively, 89% (SD 23), 95% (SD 7), and 78% (SD 44). Of
      the 7 participants who completed the usability survey, all were motivated by the
      sense of security derived from using the system, and 6 of the 7 (86%) reported
      that using SMART-D helped improve their lifestyle and self-management.
      CONCLUSIONS: Using SMART-D was feasible, and the system was well regarded by
      patients. Further study with larger scale cohorts and longer study and follow-up
      periods is needed to evaluate the effects of SMART-D on clinical outcomes and
      quality of life.

PMID- 28428169
TI  - Assessing the Medication Adherence App Marketplace From the Health Professional
      and Consumer Vantage Points.
AB  - BACKGROUND: Nonadherence produces considerable health consequences and economic
      burden to patients and payers. One approach to improve medication nonadherence
      that has gained interest in recent years is the use of smartphone adherence apps.
      The development of smartphone adherence apps has increased rapidly since 2012;
      however, literature evaluating the clinical app and effectiveness of smartphone
      adherence apps to improve medication adherence is generally lacking. OBJECTIVE:
      The aims of this study were to (1) provide an updated evaluation and comparison
      of medication adherence apps in the marketplace by assessing the features,
      functionality, and health literacy (HL) of the highest-ranking adherence apps and
      (2) indirectly measure the validity of our rating methodology by determining the
      relationship between our app evaluations and Web-based consumer ratings. METHODS:
      Two independent reviewers assessed the features and functionality using a 4
      domain rating tool of all adherence apps identified based on developer claims.
      The same reviewers downloaded and tested the 100 highest-ranking apps including
      an additional domain for assessment of HL. Pearson product correlations were
      estimated between the consumer ratings and our domain and total scores. RESULTS:
      A total of 824 adherence apps were identified; of these, 645 unique apps were
      evaluated after applying exclusion criteria. The median initial score based on
      descriptions was 14 (max of 68; range 0-60). As a result, 100 of the highest
      scoring unique apps underwent user testing. The median overall user-tested score
      was 31.5 (max of 73; range 0-60). The majority of the user tested the adherence
      apps that underwent user testing reported a consumer rating score in their
      respective online marketplace. The mean consumer rating was 3.93 (SD 0.84). The
      total user-tested score was positively correlated with consumer ratings (r=.1969,
      P=.04). CONCLUSIONS: More adherence apps are available in the Web-based
      marketplace, and the quality of these apps varies considerably. Consumer ratings
      are positively but weakly correlated with user-testing scores suggesting that our
      rating tool has some validity but that consumers and clinicians may assess
      adherence app quality differently.

PMID- 28428170
TI  - Who Uses Mobile Phone Health Apps and Does Use Matter? A Secondary Data Analytics
      Approach.
AB  - BACKGROUND: Mobile phone use and the adoption of healthy lifestyle software apps
      ("health apps") are rapidly proliferating. There is limited information on the
      users of health apps in terms of their social demographic and health
      characteristics, intentions to change, and actual health behaviors. OBJECTIVE:
      The objectives of our study were to (1) to describe the sociodemographic
      characteristics associated with health app use in a recent US nationally
      representative sample; (2) to assess the attitudinal and behavioral predictors of
      the use of health apps for health promotion; and (3) to examine the association
      between the use of health-related apps and meeting the recommended guidelines for
      fruit and vegetable intake and physical activity. METHODS: Data on users of
      mobile devices and health apps were analyzed from the National Cancer Institute's
      2015 Health Information National Trends Survey (HINTS), which was designed to
      provide nationally representative estimates for health information in the United
      States and is publicly available on the Internet. We used multivariable logistic
      regression models to assess sociodemographic predictors of mobile device and
      health app use and examine the associations between app use, intentions to change
      behavior, and actual behavioral change for fruit and vegetable consumption,
      physical activity, and weight loss. RESULTS: From the 3677 total HINTS
      respondents, older individuals (45-64 years, odds ratio, OR 0.56, 95% CI 0.47-68;
      65+ years, OR 0.19, 95% CI 0.14-0.24), males (OR 0.80, 95% CI 0.66-0.94), and
      having degree (OR 2.83, 95% CI 2.18-3.70) or less than high school education (OR
      0.43, 95% CI 0.24-0.72) were all significantly associated with a reduced
      likelihood of having adopted health apps. Similarly, both age and education were
      significant variables for predicting whether a person had adopted a mobile
      device, especially if that person was a college graduate (OR 3.30). Individuals
      with apps were significantly more likely to report intentions to improve fruit
      (63.8% with apps vs 58.5% without apps, P=.01) and vegetable (74.9% vs 64.3%,
      P<.01) consumption, physical activity (83.0% vs 65.4%, P<.01), and weight loss
      (83.4% vs 71.8%, P<.01). Individuals with apps were also more likely to meet
      recommendations for physical activity compared with those without a device or
      health apps (56.2% with apps vs 47.8% without apps, P<.01). CONCLUSIONS: The main
      users of health apps were individuals who were younger, had more education,
      reported excellent health, and had a higher income. Although differences persist
      for gender, age, and educational attainment, many individual sociodemographic
      factors are becoming less potent in influencing engagement with mobile devices
      and health app use. App use was associated with intentions to change diet and
      physical activity and meeting physical activity recommendations.

PMID- 28428171
TI  - Treat addictions with evidence, not ideology.

PMID- 28428172
TI  - How are non-numerical prognostic statements interpreted and are they subject to
      positive bias?
AB  - OBJECTIVES: Frank, clear communication with family members of terminally ill or
      incapacitated patients has important implications for well-being, satisfaction
      with care and sound decision-making. However, numerical prognostic statements,
      particularly more negative ones, have been found to be interpreted in a
      positively biased manner. Less precise non-numerical statements, preferred by
      physicians, and particularly statements using threatening terms (dying vs
      surviving) may be even more subject to such biases. METHODS: Participants (N=200)
      read non-numerical prognostic statements framed in terms of dying or surviving
      and indicated their interpretation of likelihood of survival. RESULTS: Even the
      most extreme statements were not interpreted to indicate 100% likelihood of
      surviving or dying, (eg, they will definitely survive, 92.77%). The poorness of
      prognoses was associated with more optimistically biased interpretations but this
      was not, however, affected by the wording of the prognoses in terms of dying
      versus surviving. CONCLUSIONS: The findings illuminate the ways in which commonly
      used non-numeric language may be understood in numeric terms during prognostic
      discussions and provide further evidence of recipients' propensity for positive
      bias.

PMID- 28428173
TI  - Poor prognostication: hidden meanings in word choices.

PMID- 28428174
TI  - Klotho, an antiaging molecule, attenuates oxidant-induced alveolar epithelial
      cell mtDNA damage and apoptosis.
AB  - Alveolar epithelial cell (AEC) apoptosis and inadequate repair resulting from
      "exaggerated" lung aging and mitochondrial dysfunction are critical determinants
      promoting lung fibrosis. alpha-Klotho, which is an antiaging molecule that is
      expressed predominantly in the kidney and secreted in the blood, can protect lung
      epithelial cells against hyperoxia-induced apoptosis. We reasoned that Klotho
      protects AEC exposed to oxidative stress in part by maintaining mitochondrial DNA
      (mtDNA) integrity and mitigating apoptosis. We find that Klotho levels are
      decreased in both serum and alveolar type II (AT2) cells from asbestos-exposed
      mice. We show that oxidative stress reduces AEC Klotho mRNA and protein
      expression, whereas Klotho overexpression is protective while Klotho silencing
      augments AEC mtDNA damage. Compared with wild-type, Klotho heterozygous
      hypomorphic allele (kl/+) mice have increased asbestos-induced lung fibrosis due
      in part to increased AT2 cell mtDNA damage. Notably, we demonstrate that serum
      Klotho levels are reduced in wild-type but not mitochondrial catalase
      overexpressing (MCAT) mice 3 wk following exposure to asbestos and that EUK-134,
      a MnSOD/catalase mimetic, mitigates oxidant-induced reductions in AEC Klotho
      expression. Using pharmacologic and genetic silencing studies, we show that
      Klotho attenuates oxidant-induced AEC mtDNA damage and apoptosis via mechanisms
      dependent on AKT activation arising from upstream fibroblast growth factor
      receptor 1 activation. Our findings suggest that Klotho preserves AEC mtDNA
      integrity in the setting of oxidative stress necessary for preventing apoptosis
      and asbestos-induced lung fibrosis. We reason that strategies aimed at augmenting
      AEC Klotho levels may be an innovative approach for mitigating age-related lung
      diseases.

PMID- 28428175
TI  - Flavored e-cigarette liquids reduce proliferation and viability in the CALU3
      airway epithelial cell line.
AB  - E-cigarettes are generally thought of as a safer smoking alternative to
      traditional cigarettes. However, little is known about the effects of e-cigarette
      liquids (e-liquids) on the lung. Since over 7,000 unique flavors have been
      identified for purchase in the United States, our goal was to conduct a screen
      that would test whether different flavored e-liquids exhibited different toxicant
      profiles. We tested the effects of 13 different flavored e-liquids [with nicotine
      and propylene glycol/vegetable glycerin (PG/VG) serving as controls] on a lung
      epithelial cell line (CALU3). Using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay as an indicator of cell
      proliferation/viability, we demonstrated a dose-dependent decrease of MTT
      metabolism by all flavors tested. However, a group of four flavors consistently
      showed significantly greater toxicity compared with the PG/VG control, indicating
      the potential for some flavors to elicit more harmful effects than others. We
      also tested the aerosolized "vapor" from select e-liquids on cells and found
      similar dose-dependent trends, suggesting that direct e-liquid exposures are a
      justifiable first-pass screening approach for determining relative e-liquid
      toxicity. We then identified individual chemical constituents for all 13 flavors
      using gas chromatography-mass spectrometry. These data revealed that beyond
      nicotine and PG/VG, the 13 flavored e-liquids have diverse chemical constituents.
      Since all of the flavors exhibited some degree of toxicity and a diverse array of
      chemical constituents with little inhalation toxicity available, we conclude that
      flavored e-liquids should be extensively tested on a case-by-case basis to
      determine the potential for toxicity in the lung and elsewhere.

PMID- 28428177
TI  - Coca-Cola's secret influence on medical and science journalists.

PMID- 28428176
TI  - The BMJ Awards 2017: Mental Health.

PMID- 28428180
TI  - Avoid missing a rare condition by colouring your judgment purple.

PMID- 28428179
TI  - ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke
      recovery.
AB  - Angiogenic response is essential for ischemic brain repair. The von Willebrand
      factor (VWF)-cleaving protease disintegrin and metalloprotease with
      thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial
      tube formation in vitro, but there is currently no in vivo evidence supporting a
      function of ADAMTS13 in angiogenesis. Here we show that mice deficient in
      ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion,
      pericyte and smooth muscle cell coverage on microvessels, expression of the tight
      junction and basement membrane proteins, and accelerated blood-brain barrier
      (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct
      cortex at 14 days after stroke. Deficiency of VWF or anti-VWF antibody treatment
      significantly increased microvessels, perfused capillary length, and reversed
      pericyte loss and BBB changes in Adamts13-/- mice. Furthermore, we observed that
      ADAMTS13 deficiency decreased angiopoietin-2 and galectin-3 levels in the
      isolated brain microvessels, whereas VWF deficiency had the opposite effect.
      Correlating with this, overexpression of angiopoietin-2 by adenoviruses treatment
      or administration of recombinant galectin-3 normalized microvascular reductions,
      pericyte loss, and BBB breakdown in Adamts13-/- mice. The vascular changes
      induced by angiopoietin-2 overexpression and recombinant galectin-3 treatment in
      Adamts13-/- mice were abolished by the vascular endothelial growth factor
      receptor-2 antagonist SU1498. Importantly, treating wild-type mice with
      recombinant ADAMTS13 at 7 days after stroke markedly increased neovascularization
      and vascular repair and improved functional recovery at 14 days. Our results
      suggest that ADAMTS13 controls key steps of ischemic vascular remodeling and that
      recombinant ADAMTS13 is a putative therapeutic avenue for promoting stroke
      recovery.

PMID- 28428182
TI  - If your patient doesn't speak the same language as you . . .

PMID- 28428181
TI  - Irish MP calls for key documents on Pandemrix to be handed to lawyers
      representing children with narcolepsy.

PMID- 28428183
TI  - Risk and burden of adverse intrapartum-related outcomes associated with non
      cephalic and multiple birth in rural Nepal: a prospective cohort study.
AB  - OBJECTIVES: Intrapartum-related complications are the second leading cause of
      neonatal death worldwide. We estimate the community-level risk and burden of
      intrapartum-related fetal/neonatal mortality and morbidity associated with non
      cephalic and multiple birth in rural Sarlahi District, Nepal. DESIGN: Community
      based prospective cohort study. SETTING: Rural Sarlahi District, Nepal.
      PARTICIPANTS: Pregnant women residing in the study area. METHODS: We collected
      data on maternal background characteristics, conditions during labour and
      delivery, fetal presentation and multiple birth during home visits. We ran log
      binomial regression models to estimate the associations between non
      cephalic/multiple births and fresh stillbirth, early neonatal mortality and signs
      of neonatal encephalopathy, respectively, and calculated the per cent
      attributable fraction. To better understand the context under which these adverse
      birth outcomes are occurring, we also collected data on maternal awareness of non
      cephalic presentation and multiple gestation prior to delivery. PRIMARY OUTCOME
      MEASURES: Risk of experiencing fresh stillbirth, early neonatal encephalopathy
      and early neonatal mortality associated with non-cephalic and multiple birth,
      respectively. RESULTS: Non-cephalic presentation had a particularly high risk of
      fresh stillbirth (aRR 12.52 (95% CI 7.86 to 19.95), reference: cephalic
      presentation). 20.2% of all fresh stillbirths were associated with non-cephalic
      presentation. For multiple births, there was a fourfold increase in early
      neonatal mortality (aRR: 4.57 (95% CI 1.44 to 14.50), reference: singleton
      births). 3.4% of early neonatal mortality was associated with multiple gestation.
      CONCLUSIONS: Globally and in Nepal, a large percentage of stillbirths and
      neonatal mortality is associated with intrapartum-related complications. Despite
      the low incidence of non-cephalic and multiple birth, a notable proportion of
      adverse intrapartum-related outcomes is associated with these conditions. As the
      proportion of neonatal deaths attributable to intrapartum-related complications
      continues to rise, there is a need to investigate how best to advance diagnostic
      capacity and management of these conditions. TRIAL REGISTRATION NUMBER:
      NCT01177111; pre-results.

PMID- 28428185
TI  - Investments in cancer research awarded to UK institutions and the global burden
      of cancer 2000-2013: a systematic analysis.
AB  - OBJECTIVES: To systematically categorise cancer research investment awarded to
      United Kingdom (UK) institutions in the period 2000-2013 and to estimate research
      investment relative to disease burden as measured by mortality, disability
      adjusted life years (DALYs) and years lived with disability (YLDs). DESIGN:
      Systematic analysis of all open-access data. SETTING AND PARTICIPANTS: Public and
      philanthropic funding to all UK cancer research institutions, 2000-2013. MAIN
      OUTCOME MEASURES: Number and financial value of cancer research investments
      reported in 2013 UK pounds (UKL). Mortality, DALYs and YLDs data were acquired
      from the Global Burden of Disease Study. A compound metric was adapted to
      estimate research investment relative to disease burden as measured by mortality,
      DALYs and YLDs. RESULTS: We identified 4299 funded studies with a total research
      investment of L2.4 billion. The highest fundings by anatomical sites were
      haematological, breast, prostate, colorectal and ovarian cancers. Relative to
      disease burden as determined by a compound metric combining mortality, DALYs and
      YLDs, gender-specific cancers were found to be highest funded-the five sites that
      received the most funding were prostate, ovarian, breast, mesothelioma and
      testicular cancer; the least well-funded sites were liver, thyroid, lung, upper
      gastrointestinal (GI) and bladder. Preclinical science accounted for 66.2% of
      award numbers and 62.2% of all funding. The top five areas of primary research
      focus by funding were pathogenesis, drug therapy, diagnostic, screening and
      monitoring, women's health and immunology. The largest individual funder was the
      Medical Research Council. In combination, the five lowest funded site-specific
      cancers relative to disease burden account for 47.9%, 44.3% and 20.4% of
      worldwide cancer mortality, DALYs and YLDs. CONCLUSIONS: Research funding for
      cancer is not allocated according to relative disease burden. These findings are
      in line with earlier published studies. Funding agencies and industry should
      openly document their research investments to improve better targeting of
      research investment.

PMID- 28428184
TI  - Clinical and cost-effectiveness, safety and acceptability of community
      intravenous antibiotic service models: CIVAS systematic review.
AB  - OBJECTIVE: Evaluate evidence of the efficacy, safety, acceptability and cost
      effectiveness of outpatient parenteral antimicrobial therapy (OPAT) models.
      DESIGN: A systematic review. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane
      Library, National Health Service (NHS) Economic Evaluation Database (EED),
      Research Papers in Economics (RePEc), Tufts Cost-Effectiveness Analysis (CEA)
      Registry, Health Business Elite, Health Information Management Consortium (HMIC),
      Web of Science Proceedings, International Pharmaceutical Abstracts, British
      Society for Antimicrobial Chemotherapy website. Searches were undertaken from
      1993 to 2015. STUDY SELECTION: All studies, except case reports, considering
      adult patients or practitioners involved in the delivery of OPAT were included.
      Studies combining outcomes for adults and children or non-intravenous (IV) and IV
      antibiotic groups were excluded, as were those focused on process of delivery or
      clinical effectiveness of 1 antibiotic over another. Titles/abstracts were
      screened by 1 reviewer (20% verified). 2 authors independently screened studies
      for inclusion. RESULTS: 128 studies involving >60 000 OPAT episodes were
      included. 22 studies (17%) did not indicate the OPAT model used; only 29 involved
      a comparator (23%). There was little difference in duration of OPAT treatment
      compared with inpatient therapy, and overall OPAT appeared to produce superior
      cure/improvement rates. However, when models were considered individually,
      outpatient delivery appeared to be less effective, and self-administration and
      specialist nurse delivery more effective. Drug side effects, deaths and hospital
      readmissions were similar to those for inpatient treatment, but there were more
      line-related complications. Patient satisfaction was high, with advantages seen
      in being able to resume daily activities and having greater freedom and control.
      However, most professionals perceived challenges in providing OPAT. CONCLUSIONS:
      There were no systematic differences related to the impact of OPAT on treatment
      duration or adverse events. However, evidence of its clinical benefit compared
      with traditional inpatient treatment is lacking, primarily due to the dearth of
      good quality comparative studies. There was high patient satisfaction with OPAT
      use but the few studies considering practitioner acceptability highlighted
      organisational and logistic barriers to its delivery.

PMID- 28428186
TI  - Features of alcohol harm reduction advertisements that most motivate reduced
      drinking among adults: an advertisement response study.
AB  - OBJECTIVES: To improve the effectiveness of alcohol harm reduction mass media
      campaigns, this study aimed to (1) identify existing advertisements (ads) with
      greatest potential to motivate reduced alcohol consumption, (2) assess
      consistency across audience subgroups in ad effectiveness and (3) identify ad
      features associated with effectiveness. DESIGN: Cross-sectional online ad
      response study with random assignment to view ads. PARTICIPANTS: 2174 Australian
      adult weekly drinkers recruited from an online panel. PROCEDURE: Participants
      were randomly assigned to view three of 83 English-language alcohol harm
      reduction ads. Each ad was viewed and rated by a mean of 79 participants. OUTCOME
      MEASURE: After viewing each ad, participants reported the extent to which they
      felt motivated to reduce their drinking. Ads were ranked from most to least
      motivating using predicted means adjusted for demographic characteristics and
      alcohol consumption. We compared the characteristics of the top-ranked 15% of ads
      (most motivating) with the middle 70% and bottom 15%. RESULTS: An ad about the
      link between alcohol and cancer ('Spread') was most motivating, whereas an ad
      that encouraged drinking water instead of beer ('Add nothing') was least
      motivating. Top-ranked ads were more likely than other ads to feature a 'why
      change' message and less likely to carry a 'how to change' message; more likely
      to address long-term harms; more likely to be aimed at the general adult drinking
      population and more likely to include drinking guidelines. There was substantial
      overlap in top-ranked ads for younger versus older adults, men versus women and
      high-risk versus low-risk drinker subgroups. CONCLUSIONS: The effectiveness of
      alcohol harm reduction campaigns may be improved by directly communicating
      alcohol's long-term harms to the general adult population of drinkers along with
      drinking guidelines. By doing so, campaigns can also efficiently influence high
      risk drinkers and key demographic subgroups.

PMID- 28428189
TI  - A painful wrist after a fall.

PMID- 28428187
TI  - Zambian Peer Educators for HIV Self-Testing (ZEST) study: rationale and design of
      a cluster randomised trial of HIV self-testing among female sex workers in
      Zambia.
AB  - BACKGROUND: HIV testing and knowledge of status are starting points for HIV
      treatment and prevention interventions. Among female sex workers (FSWs), HIV
      testing and status knowledge remain far from universal. HIV self-testing (HIVST)
      is an alternative to existing testing services for FSWs, but little evidence
      exists how it can be effectively and safely implemented. Here, we describe the
      rationale and design of a cluster randomised trial designed to inform
      implementation and scale-up of HIVST programmes for FSWs in Zambia. METHODS: The
      Zambian Peer Educators for HIV Self-Testing (ZEST) study is a 3-arm cluster
      randomised trial taking place in 3 towns in Zambia. Participants (N=900) are
      eligible if they are women who have exchanged sex for money or goods in the
      previous 1 month, are HIV negative or status unknown, have not tested for HIV in
      the previous 3 months, and are at least 18 years old. Participants are recruited
      by peer educators working in their communities. Participants are randomised to 1
      of 3 arms: (1) direct distribution (in which they receive an HIVST from the peer
      educator directly); (2) fixed distribution (in which they receive a coupon with
      which to collect the HIVST from a drug store or health post) or (3) standard of
      care (referral to existing HIV testing services only, without any offer of
      HIVST). Participants are followed at 1 and 4 months following distribution of the
      first HIVST. The primary end point is HIV testing in the past month measured at
      the 1-month and 4-month visits. ETHICS AND DISSEMINATION: This study was approved
      by the Institutional Review Boards at the Harvard T.H. Chan School of Public
      Health in Boston, USA and ERES Converge in Lusaka, Zambia. The findings of this
      trial will be presented at local, regional and international meetings and
      submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER:
      Pre-results; NCT02827240.

PMID- 28428190
TI  - In Vivo Detection of EGFRvIII in Glioblastoma via Perfusion Magnetic Resonance
      Imaging Signature Consistent with Deep Peritumoral Infiltration: The phi-Index.
AB  - Purpose: The epidermal growth factor receptor variant III (EGFRvIII) mutation has
      been considered a driver mutation and therapeutic target in glioblastoma, the
      most common and aggressive brain cancer. Currently, detecting EGFRvIII requires
      postoperative tissue analyses, which are ex vivo and unable to capture the
      tumor's spatial heterogeneity. Considering the increasing evidence of in vivo
      imaging signatures capturing molecular characteristics of cancer, this study aims
      to detect EGFRvIII in primary glioblastoma noninvasively, using routine
      clinically acquired imaging.Experimental Design: We found peritumoral
      infiltration and vascularization patterns being related to EGFRvIII status. We
      therefore constructed a quantitative within-patient peritumoral heterogeneity
      index (PHI/phi-index), by contrasting perfusion patterns of immediate and distant
      peritumoral edema. Application of phi-index in preoperative perfusion scans of
      independent discovery (n = 64) and validation (n = 78) cohorts, revealed the
      generalizability of this EGFRvIII imaging signature.Results: Analysis in both
      cohorts demonstrated that the obtained signature is highly accurate (89.92%),
      specific (92.35%), and sensitive (83.77%), with significantly distinctive ability
      (P = 4.0033 * 10-10, AUC = 0.8869). Findings indicated a highly infiltrative
      migratory phenotype for EGFRvIII+ tumors, which displayed similar perfusion
      patterns throughout peritumoral edema. Contrarily, EGFRvIII- tumors displayed
      perfusion dynamics consistent with peritumorally confined vascularization,
      suggesting potential benefit from extensive peritumoral
      resection/radiation.Conclusions: This EGFRvIII signature is potentially suitable
      for clinical translation, since obtained from analysis of clinically acquired
      images. Use of within-patient heterogeneity measures, rather than population
      based associations, renders phi-index potentially resistant to inter-scanner
      variations. Overall, our findings enable noninvasive evaluation of EGFRvIII for
      patient selection for targeted therapy, stratification into clinical trials,
      personalized treatment planning, and potentially treatment-response evaluation.
      Clin Cancer Res; 23(16); 4724-34. (c)2017 AACR.

PMID- 28428191
TI  - The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and
      Drug Development: Current Value and Future Applications.
AB  - Treatment of myeloma has benefited from the introduction of more effective and
      better tolerated agents, improvements in supportive care, better understanding of
      disease biology, revision of diagnostic criteria, and new sensitive and specific
      tools for disease prognostication and management. Assessment of minimal residual
      disease (MRD) in response to therapy is one of these tools, as longer progression
      free survival (PFS) is seen consistently among patients who have achieved MRD
      negativity. Current therapies lead to unprecedented frequency and depth of
      response, and next-generation flow and sequencing methods to measure MRD in bone
      marrow are in use and being developed with sensitivities in the range of 10-5 to
      10-6 cells. These technologies may be combined with functional imaging to detect
      MRD outside of bone marrow. Moreover, immune profiling methods are being
      developed to better understand the immune environment in myeloma and response to
      immunomodulatory agents while methods for molecular profiling of myeloma cells
      and circulating DNA in blood are also emerging. With the continued development
      and standardization of these methodologies, MRD has high potential for use in
      gaining new drug approvals in myeloma. The FDA has outlined two pathways by which
      MRD could be qualified as a surrogate endpoint for clinical studies directed at
      obtaining accelerated approval for new myeloma drugs. Most importantly, better
      understanding of MRD should also contribute to better treatment monitoring.
      Potentially, MRD status could be used as a prognostic factor for making treatment
      decisions and for informing timing of therapeutic interventions. Clin Cancer Res;
      23(15); 3980-93. (c)2017 AACR.

PMID- 28428192
TI  - Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in
      Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors.
AB  - Purpose: Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are
      slow-growing tumors, which frequently express somatostatin receptors on their
      cell membranes. These receptors are targets for therapy with Lutetium-177-labeled
      somatostatin analogues. We have treated over 1,200 patients with peptide receptor
      radionuclide therapy (PRRT) with [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE)
      since the year 2000 and present the results on efficacy, survival, and toxicity
      of this therapy.Experimental Design: For safety analysis, 610 patients treated
      with a cumulative dose of at least 100 mCi (3.7 GBq) 177Lu-DOTATATE were
      included. A subgroup of 443 Dutch patients who were treated with a cumulative
      dose of at least 600 mCi (22.2 GBq) 177Lu-DOTATATE before 2013 was further
      analyzed for efficacy and survival.Results: The objective response rate of the
      total group of patients was 39%. Stable disease was reached in 43% of patients.
      Progression-free survival (PFS) and overall survival (OS) for all NET patients
      were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95%
      CI, 55-72 months). Long-term toxicity included acute leukemia in four patients
      (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related
      long-term renal or hepatic failure occurred.Conclusions: PRRT with 177Lu-DOTATATE
      is a favorable therapeutic option in patients with metastatic bronchial and
      gastroenteropancreatic NETs that express somatostatin receptors. PRRT with 177Lu
      DOTATATE is safe with few side-effects and shows good response rates with PFS of
      29 months and OS of 63 months. Clin Cancer Res; 23(16); 4617-24. (c)2017 AACR.

PMID- 28428193
TI  - PD-L1 Expression in Melanoma: A Quantitative Immunohistochemical Antibody
      Comparison.
AB  - Purpose: PD-L1 expression in the pretreatment tumor microenvironment enriches for
      response to anti-PD-1/PD-L1 therapies. The purpose of this study was to
      quantitatively compare the performance of five monoclonal anti-PD-L1 antibodies
      used in recent landmark publications.Experimental Design: PD-L1 IHC was performed
      on 34 formalin-fixed paraffin-embedded archival melanoma samples using the 5H1,
      SP142, 28-8, 22C3, and SP263 clones. The percentage of total cells (including
      melanocytes and immune cells) demonstrating cell surface PD-L1 staining, as well
      as intensity measurements/H-scores, were assessed for each melanoma specimen
      using a computer-assisted platform. Staining properties were compared between
      antibodies.Results: Strong correlations were observed between the percentage of
      PD-L1(+) cells across all clones studied (R2 = 0.81-0.96). When present,
      discordant results were attributable to geographic heterogeneity of the melanoma
      tissue section rather than differences in PD-L1 antibody staining
      characteristics. PD-L1 intensity/H-scores strongly correlated with percentage of
      PD-L1(+) cells (R2 > 0.78, all clones).Conclusions: The 5H1, SP142, 28-8, 22C3,
      and SP263 clones all demonstrated similar performance characteristics when used
      in a standardized IHC assay on melanoma specimens. Reported differences in PD-L1
      IHC assays using these antibodies are thus most likely due to assay
      characteristics beyond the antibody itself. Our findings also argue against the
      inclusion of an intensity/H-score in chromogenic PD-L1 IHC assays. Clin Cancer
      Res; 23(16); 4938-44. (c)2017 AACR.

PMID- 28428197
TI  - Unusual positional effects on flower sex in an andromonoecious tree: Resource
      competition, architectural constraints, or inhibition by the apical flower?
AB  - PREMISE OF THE STUDY: Two, nonmutually exclusive, mechanisms-competition for
      resources and architectural constraints-have been proposed to explain the
      proximal to distal decline in flower size, mass, and/or femaleness in
      indeterminate, elongate inflorescences. Whether these mechanisms also explain
      unusual positional effects such as distal to proximal declines of floral
      performance in determinate inflorescences, is understudied. METHODS: We tested
      the relative influence of these mechanisms in the andromonoecious wild olive
      tree, where hermaphroditic flowers occur mainly on apical and the most proximal
      positions in determinate inflorescences. We experimentally increased the
      availability of resources for the inflorescences by removing half of the
      inflorescences per twig or reduced resource availability by removing leaves. We
      also removed the apical flower to test its inhibitory effect on subapical
      flowers. KEY RESULTS: The apical flower had the highest probability of being
      hermaphroditic. Further down, however, the probability of finding a
      hermaphroditic flower decreased from the base to the tip of the inflorescences.
      An experimental increase of resources increased the probability of finding
      hermaphroditic flowers at each position, and vice versa. Removal of the apical
      flower increased the probability of producing hermaphroditic flowers in proximal
      positions but not in subapical positions. CONCLUSIONS: These results indicate an
      interaction between resource competition and architectural constraints in
      influencing the arrangement of the hermaphroditic and male flowers within the
      inflorescences of the wild olive tree. Subapical flowers did not seem to be
      hormonally suppressed by apical flowers. The study of these unusual positional
      effects is needed for a general understanding about the functional implications
      of inflorescence architecture.

PMID- 28428194
TI  - Detrimental Effects of Centrally Administered Angiotensin II are Enhanced in a
      Mouse Model of Alzheimer Disease Independently of Blood Pressure.
AB  - BACKGROUND: The significance of brain angiotensin II in Alzheimer disease (AD) is
      unclear. METHODS AND RESULTS: To examine the role of brain angiotensin II in AD,
      intracerebroventricular angiotensin II infusion was performed on 5XFAD mice, a
      mouse model of AD, and wild-type mice, and the detrimental effects of brain
      angiotensin II was compared between the 2 strains of mice.
      Intracerebroventricular angiotensin II infusion significantly impaired cognitive
      function in 5XFAD mice but not in wild-type mice. This vulnerability of 5XFAD
      mice to brain angiotensin II was associated with enhancement of hippocampal
      inflammation and oxidative stress and with increased cerebrovascular amyloid beta
      deposition. We also compared the effect of brain angiotensin II on the heart and
      skeletal muscle between the 2 strains because AD is associated with heart failure
      and sarcopenia. We found that cardiac compensatory response of 5XFAD mice to
      brain angiotensin II-induced hypertension was less than that of wild-type mice.
      Brain angiotensin II caused skeletal muscle atrophy and injury in 5XFAD mice more
      than in wild-type mice. CONCLUSIONS: Brain angiotensin II seems to be involved in
      cognitive impairment and brain injury in AD, which is associated with oxidative
      stress, inflammation, and cerebral amyloid angiopathy. Further, brain angiotensin
      II may participate in cardiac disease and sarcopenia observed in AD.

PMID- 28428198
TI  - Correlation, causation, and the evolution of leaf teeth: A reply to Givnish and
      Kriebel.

PMID- 28428195
TI  - Progression of Coronary Artery Calcium and Incident Heart Failure: The Multi
      Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Although the association between coronary artery calcium (CAC) and
      future heart failure (HF) has been shown previously, the value of CAC progression
      in the prediction of HF has not been investigated. In this study, we investigated
      the association of CAC progression with subclinical left ventricular (LV)
      dysfunction and incident HF in the Multi-Ethnic Study of Atherosclerosis. METHODS
      AND RESULTS: The Multi-Ethnic Study of Atherosclerosis is a population-based
      study consisting of 6814 men and women aged 45 to 84, free of overt
      cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We
      included 5644 Multi-Ethnic Study of Atherosclerosis participants who had baseline
      and follow-up cardiac computed tomography and were free of HF and coronary heart
      disease before the second cardiac computed tomography. Mean (+/-SD) age was
      61.7+/-10.2 years and 47.2% were male. The Cox proportional hazard models and
      multivariable linear regression models were deployed to determine the association
      of CAC progression with incident HF and subclinical LV dysfunction, respectively.
      Over a median follow-up of 9.6 (interquartile range: 8.8-10.6) years, 182
      participants developed incident HF. CAC progression of 10 units per year was
      associated with 3% of increased risk of HF independent of overt coronary heart
      disease (P=0.008). In 2818 participants with available cardiac magnetic resonance
      images, CAC progression was associated with increased LV end diastolic volume
      (beta=0.16; P=0.03) and LV end systolic volume (beta=0.12; P=0.006) after
      excluding participants with any coronary heart disease. CONCLUSIONS: CAC
      progression was associated with incident HF and modestly increased LV end
      diastolic volume and LV end systolic volume at follow-up exam independent of
      overt coronary heart disease.

PMID- 28428199
TI  - Experimental insights on Darwin's cross-promotion hypothesis in tristylous purple
      loosestrife (Lythrum salicaria).
AB  - PREMISE OF THE STUDY: Darwin proposed that the reciprocal arrangement of anthers
      and stigmas in heterostylous plants promotes cross-pollination through pollen
      segregation on pollinators' bodies. The floral tube in most heterostylous species
      constrains the feeding posture of pollinators determining the site of contact
      with sex organs located at different heights within a flower. Here, we evaluate
      Darwin's hypothesis in tristylous Lythrum salicaria, a species with a partially
      tubular corolla, and examine the extent to which the location of sex organs
      within a flower influence compatible and incompatible pollination. We predicted
      that the proficiency of cross-pollination would increase for more inserted sex
      organs due to the restrictions imposed by the floral tube on pollinator
      positioning. METHODS: We used experimental trimorphic and monomorphic arrays and
      emasculated flowers to quantify intermorph pollen transfer and capture among all
      sex-organ heights, and estimated the contribution of intraflower self
      pollination, geitonogamous self-pollination, and intramorph outcross pollination
      to total intramorph pollination. KEY RESULTS: As predicted, disassortative
      pollination varied significantly with sex-organ height and was highest for short
      level organs and lowest for long-level organs. In monomorphic arrays, most
      intramorph pollination resulted from outcross pollination followed by intraflower
      and geitonogamous self-pollination. CONCLUSIONS: Our results provide evidence for
      the Darwinian hypothesis. Reciprocal herkogamy promoted varying degrees of
      disassortative pollination with the magnitude strongly influenced by sex-organ
      height within a flower.

PMID- 28428200
TI  - The evolution of aluminum accumulation in ferns and lycophytes.
AB  - PREMISE OF THE STUDY: This paper investigates the occurrence and evolution of
      aluminum (Al) accumulation within ferns and lycophytes, which is characterized by
      Al concentrations above 1000 mg.kg-1 in aboveground plant tissues. We hypothesize
      that this feature is more common in ferns than in angiosperms, and potentially
      correlated with growth form and other chemical elements. METHODS: Aluminum
      concentrations were obtained from novel analyses and literature for a total of
      354 specimens and 307 species. Moreover, a semiquantitative aluminon test was
      applied for a subset of 105 species and validated against exact Al measurements.
      KEY RESULTS: Molecular phylogenetic analyses showed that the major Al
      accumulating groups were primarily found in the Gleicheniales and Cyatheales, and
      largely absent in the Polypodiales. At the species and generic level, Al
      accumulation was typically either absent or present, and mixed results within a
      single species and genus were limited to less than 30% of the species and genera
      tested. Epiphytic ferns had significantly lower Al levels than terrestrial ferns,
      although this finding was not significant after phylogenetic correction. In
      addition, a significant, positive correlation was found between Al and iron,
      while Al was negatively correlated with phosphorus and potassium concentrations.
      CONCLUSIONS: Aluminum accumulation is most common outside of the Polypodiales and
      occurs in 38% of the species studied, indicating that this trait is indeed common
      within subtropical and tropical ferns, a finding that could be in line with their
      role as pioneer species on landslides and soils with high levels of soluble Al.

PMID- 28428201
TI  - Dihydrolipoamide dehydrogenase-Lpd (Rv0462)-specific T cell recall responses are
      higher in healthy household contacts of TB: a novel immunodominant antigen from
      M. tuberculosis.
AB  - The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the
      existing tuberculosis (TB) vaccine, bacillus Calmette-Guerin (BCG), highlights
      the need for novel vaccines to replace or improve BCG. In TB immunology, antigen
      specific cellular immune response is frequently considered indispensable. Latency
      associated antigens are intriguing as targets for TB vaccine development. The
      mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third
      enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium
      tuberculosis to resist host reactive nitrogen intermediates. Multicolor flow
      cytometry analysis of whole-blood cultures showed higher Lpd-specific Th1 recall
      response (IFN-gamma, TNF-alpha, and IL-2; P = 0.0006) and memory CD4+ and CD8+ T
      cells (CCR7+ CD45RA- and CCR7- CD45RA-) in healthy household contacts (HHC) of TB
      (P < 0.0001), which is comparable with or higher than the standard antigens, ESAT
      6 and CFP-10. The frequency of Lpd-specific multifunctional T cells was higher in
      HHC compared with PTB patients. However, there is no significant statistical
      correlation. Regulatory T cell (Treg) analysis of HHCs and active TB patients
      demonstrated very low Lpd-specific CD4+ Tregs relative to ESAT-6 and CFP-10. Our
      study demonstrates that the Lpd antigen induces a strong cellular immune response
      in healthy mycobacteria-infected individuals. In consideration of this population
      having demonstrated immunologic protection against active TB disease development,
      our data are encouraging about the possible use of Lpd as a target for further TB
      subunit vaccine development.

PMID- 28428202
TI  - Precision physiology and rescue of brain ion channel disorders.
AB  - Ion channel genes, originally implicated in inherited excitability disorders of
      muscle and heart, have captured a major role in the molecular diagnosis of
      central nervous system disease. Their arrival is heralded by neurologists
      confounded by a broad phenotypic spectrum of early-onset epilepsy, autism, and
      cognitive impairment with few effective treatments. As detection of rare
      structural variants in channel subunit proteins becomes routine, it is apparent
      that primary sequence alone cannot reliably predict clinical severity or pinpoint
      a therapeutic solution. Future gains in the clinical utility of variants as
      biomarkers integral to clinical decision making and drug discovery depend on our
      ability to unravel complex developmental relationships bridging single ion
      channel structure and human physiology.

PMID- 28428203
TI  - TSLP-activated dendritic cells induce human T follicular helper cell
      differentiation through OX40-ligand.
AB  - T follicular helper cells (Tfh) are important regulators of humoral responses.
      Human Tfh polarization pathways have been thus far associated with Th1 and Th17
      polarization pathways. How human Tfh cells differentiate in Th2-skewed
      environments is unknown. We show that thymic stromal lymphopoietin (TSLP)
      activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4
      T cells. We identified a novel population, distinct from Th2 cells, expressing IL
      21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed
      CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers.
      Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells,
      and this depended on IL-4Ralpha. TSLP-activated DCs stimulated circulating memory
      Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh
      differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results
      delineate a pathway of human Tfh differentiation in Th2 environments.

PMID- 28428204
TI  - Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial
      Injury via TLR2 in Mice: Implications for Superficial Erosion.
AB  - RATIONALE: Superficial erosion currently causes up to a third of acute coronary
      syndromes; yet, we lack understanding of its mechanisms. Thrombi because of
      superficial intimal erosion characteristically complicate matrix-rich atheromata
      in regions of flow perturbation. OBJECTIVE: This study tested in vivo the
      involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like
      receptor 2 ligation in superficial intimal injury, a process implicated in
      superficial erosion. METHODS AND RESULTS: In mouse carotid arteries with
      established intimal lesions tailored to resemble the substrate of human eroded
      plaques, acute flow perturbation promoted downstream endothelial cell activation,
      neutrophil accumulation, endothelial cell death and desquamation, and mural
      thrombosis. Neutrophil loss-of-function limited these findings. Toll-like
      receptor 2 agonism activated luminal endothelial cells, and deficiency of this
      innate immune receptor decreased intimal neutrophil adherence in regions of local
      flow disturbance, reducing endothelial cell injury and local thrombosis (P<0.05).
      CONCLUSIONS: These results implicate flow disturbance, neutrophils, and Toll-like
      receptor 2 signaling as mechanisms that contribute to superficial erosion, a
      cause of acute coronary syndrome of likely growing importance in the statin era.

PMID- 28428205
TI  - Measurable Supratentorial White Matter Volume Changes in Patients with Diffuse
      Intrinsic Pontine Glioma Treated with an Anti-Vascular Endothelial Growth Factor
      Agent, Steroids, and Radiation.
AB  - BACKGROUND AND PURPOSE: Assessing the response to treatment in infiltrative brain
      tumors by using lesion volume-based response criteria is challenging. We
      hypothesized that in such tumors, volume measurements alone may not accurately
      capture changes in actual tumor burden during treatment. We longitudinally
      evaluated volume changes in both normal-appearing supratentorial white matter and
      the brain stem lesions in patients treated for diffuse intrinsic pontine glioma
      to determine to what extent adjuvant systemic therapies may skew the accuracy of
      tumor response assessments based on volumetric analysis. MATERIALS AND METHODS:
      The anatomic MR imaging and diffusion tensor imaging data of 26 patients with
      diffuse intrinsic pontine glioma were retrospectively analyzed. Treatment
      included conformal radiation therapy in conjunction with vandetanib and
      dexamethasone. Volumetric and diffusion data were analyzed with time, and
      differences between time points were evaluated statistically. RESULTS: Normalized
      brain stem lesion volume decreased during combined treatment (slope = -0.222, P <
      .001) and increased shortly after completion of radiation therapy (slope = 0.422,
      P < .001). Supratentorial white matter volume steadily and significantly
      decreased with time (slope = -0.057, P < .001). CONCLUSIONS: Longitudinal changes
      in brain stem lesion volume are robust; less pronounced but measurable changes
      occur in the supratentorial white matter. Volume changes in nonirradiated
      supratentorial white matter during the disease course reflect the effects of
      systemic medication on the water homeostasis of normal parenchyma. Our data
      suggest that adjuvant nontumor-targeted therapies may have a more substantial
      effect on lesion volume changes than previously thought; hence, an apparent
      volume decrease in infiltrative tumors receiving combined therapies may lead to
      overestimation of the actual response and tumor control.

PMID- 28428206
TI  - Current and Emerging Therapies in Multiple Sclerosis: Implications for the
      Radiologist, Part 2-Surveillance for Treatment Complications and Disease
      Progression.
AB  - An understanding of the new generation of MS drugs in conjunction with the key
      role MR imaging plays in the detection of disease progression, opportunistic
      infections, and drug-related adverse effects is of vital importance to the
      neuroradiologist. Part 1 of this review outlined the current treatment options
      available for MS and examined the mechanisms of action of the various
      medications. It also covered specific complications associated with each form of
      therapy. Part 2, in turn deals with the subject of pharmacovigilance and the
      optimal frequency of MRI monitoring for each individual patient, depending on his
      or her unique risk profile. Special attention is given to the diagnosing of
      progressive multifocal leukoencephalopathy in patients treated with natalizumab
      as this is a key area in which neuroradiologists can contribute to improved
      patient outcomes. This article also outlines the aims of treatment and reviews
      the possibility of "no evidence of disease activity" becoming a treatment goal
      with the availability of more effective therapies. Potential future areas and
      technologies including image subtraction, brain volume measurement and advanced
      imaging techniques such as double inversion recovery are also reviewed. It is
      anticipated that such advancements in this rapidly developing field will improve
      the accuracy of monitoring an individual patient's response to treatment.

PMID- 28428207
TI  - MR Imaging Grading System for Skull Base Chordoma.
AB  - BACKGROUND AND PURPOSE: Skull base chordoma has been widely studied in recent
      years, however, imaging characteristics of this tumor have not been well
      elaborated. The purpose of this study was to establish an MR imaging grading
      system for skull base chordoma. MATERIALS AND METHODS: In this study, 156
      patients with skull base chordomas were retrospectively assessed. Tumor-to-pons
      signal intensity ratios were calculated from pretreatment MR images RT1 (ratio of
      tumor to pons signal intensity in T1 FLAIR sequence), RT2 (ratio of tumor to pons
      signal intensity in T2 sequence) and REN (ratio of tumor to pons signal intensity
      in enhanced T1 FLAIR sequence), and significant ratios for overall survival and
      progression-free survival were selected to establish a grading system. Clinical
      variables among different MR imaging grades were then analyzed to evaluate the
      usefulness of the grading system. RESULTS: RT2 (P < .001) and REN (P = .04) were
      identified as significant variables affecting progression-free survival. After
      analysis, the classification criteria were set as follows: MR grade I, RT2 > 2.49
      and REN <= 0.77; MR grade II, RT2 > 2.49 and REN > 0.77, or RT2 <= 2.49 and REN
      <= 0.77; and MR grade III, RT2 <= 2.49 and REN > 0.77. MR grade III tumors had a
      more abundant tumor blood supply than MR grade I tumors (P < .001), and the
      intraoperative blood loss of MR grade III tumors was higher than that of MR grade
      I tumors (P = .002). Additionally, skull base chordoma progression risk increased
      by 2.071 times for every single MR grade increase (P < .001). CONCLUSIONS: A
      higher RT2 value was a negative indicator of tumor progression, whereas a higher
      REN value was a positive risk factor of tumor progression. MR grade III tumors
      showed a more abundant blood supply than MR grade I tumors, and the risk of skull
      base chordoma progression increased with every single MR grade increase.

PMID- 28428208
TI  - Resting-State Seed-Based Analysis: An Alternative to Task-Based Language fMRI and
      Its Laterality Index.
AB  - BACKGROUND AND PURPOSE: Language is a cardinal function that makes human unique.
      Preservation of language function poses a great challenge for surgeons during
      resection. The aim of the study was to assess the efficacy of resting-state fMRI
      in the lateralization of language function in healthy subjects to permit its
      further testing in patients who are unable to perform task-based fMRI. MATERIALS
      AND METHODS: Eighteen healthy right-handed volunteers were prospectively
      evaluated with resting-state fMRI and task-based fMRI to assess language
      networks. The laterality indices of Broca and Wernicke areas were calculated by
      using task-based fMRI via a voxel-value approach. We adopted seed-based resting
      state fMRI connectivity analysis together with parameters such as amplitude of
      low-frequency fluctuation and fractional amplitude of low-frequency fluctuation
      (fALFF). Resting-state fMRI connectivity maps for language networks were obtained
      from Broca and Wernicke areas in both hemispheres. We performed correlation
      analysis between the laterality index and the z scores of functional
      connectivity, amplitude of low-frequency fluctuation, and fALFF. RESULTS: Pearson
      correlation analysis between signals obtained from the z score of fALFF and the
      laterality index yielded a correlation coefficient of 0.849 (P < .05). Regression
      analysis of the fALFF with the laterality index yielded an R2 value of 0.721,
      indicating that 72.1% of the variance in the laterality index of task-based fMRI
      could be predicted from the fALFF of resting-state fMRI. CONCLUSIONS: The present
      study demonstrates that fALFF can be used as an alternative to task-based fMRI
      for assessing language laterality. There was a strong positive correlation
      between the fALFF of the Broca area of resting-state fMRI with the laterality
      index of task-based fMRI. Furthermore, we demonstrated the efficacy of fALFF for
      predicting the laterality of task-based fMRI.

PMID- 28428209
TI  - Myelin Detection Using Rapid Quantitative MR Imaging Correlated to
      Macroscopically Registered Luxol Fast Blue-Stained Brain Specimens.
AB  - BACKGROUND AND PURPOSE: Myelin detection is of great value in monitoring diseases
      such as multiple sclerosis and dementia. However, most MR imaging methods to
      measure myelin are challenging for routine clinical use. Recently, a novel method
      was published, in which the presence of myelin is inferred by using its effect on
      the intra- and extracellular water relaxation rates and proton density,
      observable by rapid quantitative MR imaging. The purpose of this work was to
      validate this method further on the brains of 12 fresh, intact cadavers.
      MATERIALS AND METHODS: The 12 brains were scanned with a quantification sequence
      to determine the longitudinal and transverse relaxation rates and proton density
      as input for the myelin estimations. Subsequently, the brains were excised at
      postmortem examination, and brain slices were stained with Luxol fast blue to
      verify the presence of myelin. The optical density values of photographs of the
      stained brain slices were registered with the MR images and correlated with the
      myelin estimation performed by quantitative MR imaging. RESULTS: A correlation
      was found between the 2 methods with a mean Spearman rho for all subjects of 0.74
      +/- 0.11. Linear regression showed a mean intercept of 1.50% +/- 2.84% and a mean
      slope of 4.37% +/- 1.73%/%. A lower correlation was found for the separate
      longitudinal relaxation rates and proton density (rho = 0.63 +/- 0.12 and -0.73
      +/- 0.09, respectively). For transverse relaxation rates, the rho was very low
      (0.11 +/- 0.28). CONCLUSIONS: The observed correlation supports the validity of
      myelin measurement by using the MR imaging quantification method.

PMID- 28428210
TI  - Proton Chemical Shift Imaging Study of the Combined Antiretroviral Therapy Impact
      on Neurometabolic Parameters in Chronic HIV Infection.
AB  - BACKGROUND AND PURPOSE: The introduction of combination antiretroviral therapy
      has failed to reduce the high prevalence of mild forms of HIV-associated
      neurocognitive disorders. The aim of this study was to test the effect of
      combined antiretroviral therapy on brain metabolite ratios in chronic HIV
      infection by using proton chemical shift imaging. MATERIALS AND METHODS: We
      performed 2D chemical shift imaging in 91 subjects (31 HIV+ patients with chronic
      infection on combination antiretroviral therapy, 19 combination antiretroviral
      therapy-naive HIV+ subjects with chronic infection, and 41 healthy controls),
      covering frontal and parietal subcortical white and cingulate gyrus gray matter,
      analyzing ratios of NAA/Cr and Cho/Cr on long-TE and mIns/Cr on short-TE MR
      spectroscopy. We correlated neurometabolic parameters with immunologic, clinical,
      data and combined antiretroviral therapy efficacy scores. RESULTS: There was a
      significant decrease in NAA/Cr (P < .05) in HIV-positive patients on and without
      combined antiretroviral therapy, compared with healthy controls in all locations.
      There were significant differences in Cho/Cr (P < .05) and mIns/Cr (P < .05)
      ratios between HIV+ patients on and without therapy, compared with healthy
      controls, but these differed in distribution. There were no significant
      differences in brain metabolite ratios between the 2 groups of chronically HIV
      infected patients. The CNS penetration efficacy score showed weak positive
      correlations only with Cho/Cr ratios in some locations. CONCLUSIONS: The impact
      of combined antiretroviral therapy on the process of neuronal loss and
      dysfunction in chronic HIV infection appears to be suboptimal in successful
      peripheral suppression of viral replication. Spectroscopic imaging might be a
      useful tool for monitoring the effects of different combined antiretroviral
      therapy regimens on brain metabolite ratios.

PMID- 28428211
TI  - Imaging Manifestations of Pseudoprogression in Metastatic Melanoma Nodes Injected
      with Talimogene Laherparepvec: Initial Experience.
AB  - Talimogene laherparepvec is an oncolytic virus recently approved for targeted
      treatment of advanced melanoma. Because of an inflammatory reaction, treated
      lesions may increase in size and develop infiltrative margins that can be
      construed as disease progression or extracapsular spread. In this report, we
      describe our initial experience imaging the response of metastatic nodes injected
      with talimogene laherparepvec. Six of 12 nodes (50%) showed growth from baseline
      followed by decreased size, 5 of 12 nodes (42%) showed a downward size trend, and
      1 node showed continued increase in size. Seven of 9 nodes (78%) developed
      infiltrative margins at a median of 79 days, and 6 of 9 (67%) nodes became
      necrotic at a median of 76 days after injection, all showing decreased size at
      final follow-up. An increase in the size of nodes injected with talimogene
      laherparepvec does not necessarily indicate progression. Infiltrative margins are
      also frequently seen and may be confused with extracapsular disease.

PMID- 28428212
TI  - A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White
      Matter to Gray Matter Signal Intensity Ratio.
AB  - BACKGROUND AND PURPOSE: T2*-weighted imaging provides sharp contrast between
      spinal cord GM and WM, allowing their segmentation and cross-sectional area
      measurement. Injured WM demonstrates T2*WI hyperintensity but requires
      normalization for quantitative use. We introduce T2*WI WM/GM signal-intensity
      ratio and compare it against cross-sectional area, the DTI metric fractional
      anisotropy, and magnetization transfer ratio in degenerative cervical myelopathy.
      MATERIALS AND METHODS: Fifty-eight patients with degenerative cervical myelopathy
      and 40 healthy subjects underwent 3T MR imaging, covering C1-C7. Metrics were
      automatically extracted at maximally compressed and uncompressed rostral/caudal
      levels. Normalized metrics were compared with t tests, area under the curve, and
      logistic regression. Relationships with clinical measures were analyzed by using
      Pearson correlation and multiple linear regression. RESULTS: The maximally
      compressed level cross-sectional area demonstrated superior differences (P = 1 *
      10-13), diagnostic accuracy (area under the curve = 0.890), and univariate
      correlation with the modified Japanese Orthopedic Association score (0.66). T2*WI
      WM/GM showed strong differences (rostral: P = 8 * 10-7; maximally compressed
      level: P = 1 * 10-11; caudal: P = 1 * 10-4), correlations (modified Japanese
      Orthopedic Association score; rostral: -0.52; maximally compressed level: -0.59;
      caudal: -0.36), and diagnostic accuracy (rostral: 0.775; maximally compressed
      level: 0.860; caudal: 0.721), outperforming fractional anisotropy and
      magnetization transfer ratio in most comparisons and cross-sectional area at
      rostral/caudal levels. Rostral T2*WI WM/GM showed the strongest correlations with
      focal motor (-0.45) and sensory (-0.49) deficits and was the strongest
      independent predictor of the modified Japanese Orthopedic Association score (P =
      .01) and diagnosis (P = .02) in multivariate models (R2 = 0.59, P = 8 * 10-13;
      area under the curve = 0.954, respectively). CONCLUSIONS: T2*WI WM/GM shows
      promise as a novel biomarker of WM injury. It detects damage in compressed and
      uncompressed regions and contributes substantially to multivariate models for
      diagnosis and correlation with impairment. Our multiparametric approach overcomes
      limitations of individual measures, having the potential to improve diagnostics,
      monitor progression, and predict outcomes.

PMID- 28428213
TI  - Clinically Feasible Microstructural MRI to Quantify Cervical Spinal Cord Tissue
      Injury Using DTI, MT, and T2*-Weighted Imaging: Assessment of Normative Data and
      Reliability.
AB  - BACKGROUND AND PURPOSE: DTI, magnetization transfer, T2*-weighted imaging, and
      cross-sectional area can quantify aspects of spinal cord microstructure. However,
      clinical adoption remains elusive due to complex acquisitions, cumbersome
      analysis, limited reliability, and wide ranges of normal values. We propose a
      simple multiparametric protocol with automated analysis and report normative
      data, analysis of confounding variables, and reliability. MATERIALS AND METHODS:
      Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at
      3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional
      area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal
      intensity ratio were calculated. Relationships between MR imaging metrics and
      age, sex, height, weight, cervical cord length, and rostrocaudal level were
      analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17
      magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac
      triggering was compared in 10 subjects. RESULTS: T2*WI WM/GM showed lower
      intersubject coefficient of variation (3.5%) compared with magnetization transfer
      ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%).
      Linear correction of cross-sectional area with cervical cord length, fractional
      anisotropy with age, and magnetization transfer ratio with age and height led to
      decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively).
      Acceptable reliability was achieved for all metrics/levels (test-retest
      coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with
      fractional anisotropy and magnetization transfer ratio. DTI with and without
      cardiac triggering showed no significant differences for fractional anisotropy
      and test-retest coefficient of variation. CONCLUSIONS: Reliable multiparametric
      assessment of spinal cord microstructure is possible by using clinically suitable
      methods. These results establish normalization procedures and pave the way for
      clinical studies, with the potential for improving diagnostics, objectively
      monitoring disease progression, and predicting outcomes in spinal pathologies.

PMID- 28428214
TI  - Time for an overhaul at the World Medical Association.

PMID- 28428215
TI  - Blocked transcription through KvDMR1 results in absence of methylation and gene
      silencing resembling Beckwith-Wiedemann syndrome.
AB  - The maternally methylated KvDMR1 ICR regulates imprinted expression of a cluster
      of maternally expressed genes on human chromosome 11p15.5. Disruption of
      imprinting leads to Beckwith-Wiedemann syndrome (BWS), an overgrowth and cancer
      predisposition condition. In the majority of individuals with BWS, maternal
      specific methylation at KvDMR1 is absent and genes under its control are
      repressed. We analyzed a mouse model carrying a poly(A) truncation cassette
      inserted to prevent RNA transcripts from elongation through KvDMR1. Maternal
      inheritance of this mutation resulted in absence of DNA methylation at KvDMR1,
      which led to biallelic expression of Kcnq1ot1 and suppression of maternally
      expressed genes. This study provides further evidence that transcription is
      required for establishment of methylation at maternal gametic DMRs. More
      importantly, this mouse model recapitulates the molecular phenotypic
      characteristics of the most common form of BWS, including loss of methylation at
      KvDMR1 and biallelic repression of Cdkn1c, suggesting that deficiency of maternal
      transcription through KvDMR1 may be an underlying cause of some BWS cases.

PMID- 28428216
TI  - Maturation of Platelet Function During Murine Fetal Development In Vivo.
AB  - OBJECTIVE: Platelet function has been intensively studied in the adult organism.
      However, little is known about the function and hemostatic capacity of platelets
      in the developing fetus as suitable in vivo models are lacking. APPROACH AND
      RESULTS: To examine fetal platelet function in vivo, we generated a fetal
      thrombosis model and investigated light/dye-induced thrombus formation by
      intravital microscopy throughout gestation. We observed that significantly less
      and unstable thrombi were formed at embryonic day (E) 13.5 compared with E17.5.
      Flow cytometry revealed significantly lower platelet counts in E13.5 versus E17.5
      fetuses versus adult controls. In addition, fetal platelets demonstrated changed
      activation responses of surface adhesion molecules and reduced P-selectin content
      and mobilization. Interestingly, we also measured reduced levels of the integrin
      activating proteins Kindlin-3, Talin-1, and Rap1 during fetal development.
      Consistently, fetal platelets demonstrated diminished spreading capacity compared
      with adults. Transfusion of adult platelets into the fetal circulation led to
      rapid platelet aggregate formation even in young fetuses. Yet, retrospective data
      analysis of a neonatal cohort demonstrated no correlation of platelet transfusion
      with closure of a persistent ductus arteriosus, a process reported to be platelet
      dependent. CONCLUSIONS: Taken together, we demonstrate an ontogenetic regulation
      of platelet function in vivo with physiologically low platelet numbers and
      hyporeactivity early during fetal development shedding new light on hemostatic
      function during fetal life.

PMID- 28428217
TI  - microRNA-33 Regulates Macrophage Autophagy in Atherosclerosis.
AB  - OBJECTIVE: Defective autophagy in macrophages leads to pathological processes
      that contribute to atherosclerosis, including impaired cholesterol metabolism and
      defective efferocytosis. Autophagy promotes the degradation of cytoplasmic
      components in lysosomes and plays a key role in the catabolism of stored lipids
      to maintain cellular homeostasis. microRNA-33 (miR-33) is a post-transcriptional
      regulator of genes involved in cholesterol homeostasis, yet the complete
      mechanisms by which miR-33 controls lipid metabolism are unknown. We investigated
      whether miR-33 targeting of autophagy contributes to its regulation of
      cholesterol homeostasis and atherogenesis. APPROACH AND RESULTS: Using coherent
      anti-Stokes Raman scattering microscopy, we show that miR-33 drives lipid droplet
      accumulation in macrophages, suggesting decreased lipolysis. Inhibition of
      neutral and lysosomal hydrolysis pathways revealed that miR-33 reduced
      cholesterol mobilization by a lysosomal-dependent mechanism, implicating
      repression of autophagy. Indeed, we show that miR-33 targets key autophagy
      regulators and effectors in macrophages to reduce lipid droplet catabolism, an
      essential process to generate free cholesterol for efflux. Notably, miR-33
      regulation of autophagy lies upstream of its known effects on ABCA1 (ATP-binding
      cassette transporter A1)-dependent cholesterol efflux, as miR-33 inhibitors fail
      to increase efflux upon genetic or chemical inhibition of autophagy. Furthermore,
      we find that miR-33 inhibits apoptotic cell clearance via an autophagy-dependent
      mechanism. Macrophages treated with anti-miR-33 show increased efferocytosis,
      lysosomal biogenesis, and degradation of apoptotic material. Finally, we show
      that treating atherosclerotic Ldlr-/- mice with anti-miR-33 restores defective
      autophagy in macrophage foam cells and plaques and promotes apoptotic cell
      clearance to reduce plaque necrosis. CONCLUSIONS: Collectively, these data
      provide insight into the mechanisms by which miR-33 regulates cellular
      cholesterol homeostasis and atherosclerosis.

PMID- 28428218
TI  - Gain-of-Function Mutation in Filamin A Potentiates Platelet Integrin
      alphaIIbbeta3 Activation.
AB  - OBJECTIVE: Dominant mutations of the X-linked filamin A (FLNA) gene are
      responsible for filaminopathies A, which are rare disorders including brain
      periventricular nodular heterotopia, congenital intestinal pseudo-obstruction,
      cardiac valves or skeleton malformations, and often macrothrombocytopenia.
      APPROACH AND RESULTS: We studied a male patient with periventricular nodular
      heterotopia and congenital intestinal pseudo-obstruction, his unique X-linked
      FLNA allele carrying a stop codon mutation resulting in a 100-amino acid-long
      FLNa C-terminal extension (NP_001447.2: p.Ter2648SerextTer101). Platelet counts
      were normal, with few enlarged platelets. FLNa was detectable in all platelets
      but at 30% of control levels. Surprisingly, all platelet functions were
      significantly upregulated, including platelet aggregation and secretion, as
      induced by ADP, collagen, or von Willebrand factor in the presence of ristocetin,
      as well as thrombus formation in blood flow on a collagen or on a von Willebrand
      factor matrix. Most importantly, patient platelets stimulated with ADP exhibited
      a marked increase in alphaIIbbeta3 integrin activation and a parallel increase in
      talin recruitment to beta3, contrasting with normal Rap1 activation. These
      results are consistent with the mutant FLNa affecting the last step of
      alphaIIbbeta3 activation. Overexpression of mutant FLNa in the HEL megakaryocytic
      cell line correlated with an increase (compared with wild-type FLNa) in PMA
      induced fibrinogen binding to and in talin and kindlin-3 recruitment by
      alphaIIbbeta3. CONCLUSIONS: Altogether, our results are consistent with a less
      binding of mutant FLNa to beta3 and the facilitated recruitment of talin by beta3
      on platelet stimulation, explaining the increased alphaIIbbeta3 activation and
      the ensuing gain-of-platelet functions.

PMID- 28428219
TI  - Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis
      in Rabbits.
AB  - OBJECTIVE: CETP (cholesteryl ester transfer protein) plays an important role in
      lipoprotein metabolism; however, whether inhibition of CETP activity can prevent
      cardiovascular disease remains controversial. APPROACH AND RESULTS: We generated
      CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared
      their susceptibility to cholesterol diet-induced atherosclerosis to that of wild
      type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high
      density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO
      rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents.
      When challenged with a cholesterol-rich diet for 18 weeks, KO rabbits not only
      had higher HDL cholesterol levels but also lower total cholesterol levels than WT
      rabbits. Analysis of plasma lipoproteins revealed that reduced plasma total
      cholesterol in KO rabbits was attributable to decreased apolipoprotein B
      containing particles, while HDLs remained higher than that in WT rabbits. Both
      aortic and coronary atherosclerosis was significantly reduced in KO rabbits
      compared with WT rabbits. Apolipoprotein B-depleted plasma isolated from CETP KO
      rabbits showed significantly higher capacity for cholesterol efflux from
      macrophages than that from WT rabbits. Furthermore, HDLs isolated from CETP KO
      rabbits suppressed tumor necrosis factor-alpha-induced vascular cell adhesion
      molecule 1 and E-selectin expression in cultured endothelial cells. CONCLUSIONS:
      These results provide evidence that genetic ablation of CETP activity protects
      against cholesterol diet-induced atherosclerosis in rabbits.

PMID- 28428220
TI  - CMTM3 (CKLF-Like Marvel Transmembrane Domain 3) Mediates Angiogenesis by
      Regulating Cell Surface Availability of VE-Cadherin in Endothelial Adherens
      Junctions.
AB  - OBJECTIVE: Decrease in VE-cadherin adherens junctions reduces vascular stability,
      whereas disruption of adherens junctions is a requirement for neovessel sprouting
      during angiogenesis. Endocytosis plays a key role in regulating junctional
      strength by altering bioavailability of cell surface proteins, including VE
      cadherin. Identification of new mediators of endothelial endocytosis could
      enhance our understanding of angiogenesis. Here, we assessed the function of
      CMTM3 (CKLF-like MARVEL transmembrane domain 3), which we have previously
      identified as highly expressed in Flk1+ endothelial progenitor cells during
      embryonic development. APPROACH AND RESULTS: Using a 3-dimensional coculture of
      human umbilical vein endothelial cells-GFP (green fluorescent protein) and
      pericytes-RFP (red fluorescent protein), we demonstrated that siRNA-mediated
      CMTM3 silencing in human umbilical vein endothelial cells impairs angiogenesis.
      In vivo CMTM3 inhibition by morpholino injection in developing zebrafish larvae
      confirmed that CMTM3 expression is required for vascular sprouting. CMTM3
      knockdown in human umbilical vein endothelial cells does not affect proliferation
      or migration. Intracellular staining demonstrated that CMTM3 colocalizes with
      early endosome markers EEA1 (early endosome marker 1) and Clathrin+ vesicles and
      with cytosolic VE-cadherin in human umbilical vein endothelial cells. Adenovirus
      mediated CMTM3 overexpression enhances endothelial endocytosis, shown by an
      increase in Clathrin+, EEA1+, Rab11+, Rab5+, and Rab7+ vesicles. CMTM3
      overexpression enhances, whereas CMTM3 knockdown decreases internalization of
      cell surface VE-cadherin in vitro. CMTM3 promotes loss of endothelial barrier
      function in thrombin-induced responses, shown by transendothelial electric
      resistance measurements in vitro. CONCLUSIONS: In this study, we have identified
      a new regulatory function for CMTM3 in angiogenesis. CMTM3 is involved in VE
      cadherin turnover and is a regulator of the cell surface pool of VE-cadherin.
      Therefore, CMTM3 mediates cell-cell adhesion at adherens junctions and
      contributes to the control of vascular sprouting.

PMID- 28428222
TI  - Evidence-Based Medicine these 7 years: time for the editor to go on permanent
      sabbatical.

PMID- 28428221
TI  - Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of
      Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts.
AB  - OBJECTIVE: Interleukin (IL)-1beta represents a key cytokine in the development of
      cardiovascular disease (CVD). IL-1beta is counter-regulated by IL-1 receptor
      antagonist (IL-1RA), an endogenous inhibitor. This study aimed to identify
      population-based studies on circulating IL-1RA and incident CVD in a systematic
      review, estimate the association between IL-1RA and incident CVD in a meta
      analysis, and to test whether the association between IL-1RA and incident CVD is
      explained by other inflammation-related biomarkers in the MONICA/KORA Augsburg
      case-cohort study (Multinational Monitoring of Trends and Determinants in
      Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg).
      APPROACH AND RESULTS: We performed a systematic literature search and identified
      5 cohort studies on IL-1RA and incident CVD in addition to the MONICA/KORA
      Augsburg case-cohort study for a meta-analysis based on a total of 1855 CVD cases
      and 18 745 noncases with follow-up times between 5 and 16 years. The pooled
      standardized hazard ratio (95% confidence interval) for incident CVD was 1.11
      (1.06-1.17) after adjustment for age, sex, anthropometric, metabolic, and
      lifestyle factors (P<0.0001). There was no heterogeneity in effect sizes (I2=0%;
      P=0.88). More detailed analyses in the MONICA/KORA study showed that the excess
      risk for CVD was attenuated by >=10% after additional separate adjustment for
      serum levels of high-sensitivity C-reactive protein, IL-6, myeloperoxidase,
      soluble E-selectin, or soluble intercellular adhesion molecule-1. CONCLUSIONS:
      Serum IL-1RA levels were positively associated with risk of CVD after adjustment
      for multiple confounders in a meta-analysis of 6 population-based cohorts. This
      association may at least partially reflect a response to triggers inducing
      subclinical inflammation, oxidative stress, and endothelial activation.

PMID- 28428223
TI  - Glutamatergic Mechanisms Involved in Bladder Overactivity and Pudendal
      Neuromodulation in Cats.
AB  - The involvement of ionotropic glutamate receptors in bladder overactivity and
      pudendal neuromodulation was determined in alpha-chloralose anesthetized cats by
      intravenously administering MK801 (a NMDA receptor antagonist) or CP465022 (an
      AMPA receptor antagonist). Infusion of 0.5% acetic acid (AA) into the bladder
      produced bladder overactivity. In the first group of 5 cats, bladder capacity was
      significantly (P < 0.05) reduced to 55.3+/-10.0% of saline control by AA
      irritation. Pudendal nerve stimulation (PNS) significantly (P < 0.05) increased
      bladder capacity to 106.8 +/- 15.0% and 106.7 +/- 13.3% of saline control at 2T
      and 4T intensity, respectively. T is threshold intensity for inducing anal
      twitching. MK801 at 0.3 mg/kg prevented the increase in capacity by 2T or 4T PNS.
      In the second group of 5 cats, bladder capacity was significantly (P < 0.05)
      reduced to 49.0 +/- 7.5% of saline control by AA irritation. It was then
      significantly (P < 0.05) increased to 80.8+/-13.5% and 79.0+/-14.0% of saline
      control by 2T and 4T PNS, respectively. CP465022 at 0.03-1 mg/kg prevented the
      increase in capacity by 2T PNS and at 0.3-1 mg/kg prevented the increase in
      capacity by 4T PNS. In both groups, MK801 at 0.3 mg/kg and CP465022 at 1 mg/kg
      significantly (P < 0.05) increased the prestimulation bladder capacity (about 80%
      and 20%, respectively) and reduced the amplitude of bladder contractions (about
      30 and 20 cmH2O, respectively). These results indicate that NMDA and AMPA
      glutamate receptors are important for PNS to inhibit bladder overactivity and
      that tonic activation of these receptors also contributes to the bladder
      overactivity induced by AA irritation.

PMID- 28428224
TI  - Familial Hypercholesterolemia and Type 2 Diabetes in the Old Order Amish.
AB  - Alleles associated with lower levels of LDL cholesterol (LDL-C) have recently
      been associated with an increased risk of type 2 diabetes (T2D), highlighting the
      complex relationship between LDL-C and diabetes. This observation begs the
      question of whether LDL-C-raising alleles are associated with a decreased risk of
      T2D. This issue was recently addressed in a large familial hypercholesterolemia
      (FH) screening study, which reported a lower prevalence of self-reported diabetes
      in FH subjects than in age-matched relatives without FH. To extend this
      observation, we tested the association of FH with diabetes status and glycemia in
      a large Amish population enriched for the FH-associated APOB R3527Q variant that
      included 640 APOB R3527Q carriers and 4,683 noncarriers. Each copy of the R3527Q
      T allele was associated with a 74.9 mg/dL increase in LDL-C. There was little
      difference in T2D prevalence between subjects with (5.2%) and without (4.5%) the
      R3527Q allele (P = 0.23), and there was no association between R3527Q variant and
      impaired fasting glucose, fasting glucose or insulin, or oral glucose tolerance
      test-derived measures. Our data provide no evidence supporting an association
      between the APOB R3527Q variant and T2D or glycemia and highlight the asymmetry
      of the LDL-C-T2D relationship and/or the gene/variant-dependent specificity of
      the LDL-C-T2D association.

PMID- 28428225
TI  - Empagliflozin and Kinetics of Renal Glucose Transport in Healthy Individuals and
      Individuals With Type 2 Diabetes.
AB  - Renal glucose reabsorption was measured with the stepped hyperglycemic clamp in
      15 subjects with type 2 diabetes mellitus (T2DM) and 15 without diabetes after 2
      days and after more chronic (14 days) treatment with empagliflozin. Patients with
      T2DM had significantly greater maximal renal glucose transport (TmG) compared
      with subjects without diabetes at baseline (459 +/- 53 vs. 337 +/- 25 mg/min; P <
      0.05). Empagliflozin treatment for 48 h reduced the TmG in both individuals with
      and without diabetes by 44 +/- 7 and 53 +/- 6%, respectively (both P < 0.001).
      TmG was further reduced by empagliflozin in both groups on day 14 (by 65 +/- 5
      and 75 +/- 3%, respectively). Empagliflozin reduced the plasma glucose
      concentration threshold for glucose spillage in the urine similarly in
      individuals with T2DM and without diabetes to <40 mg/dL, which is well below the
      normal fasting plasma glucose concentration. In summary, sodium-glucose
      transporter-2 inhibition with empagliflozin reduces both TmG and threshold for
      glucose spillage in the urine in patients with T2DM and those without diabetes.

PMID- 28428226
TI  - Rapid Throughput Analysis of GABAA Receptor Subtype Modulators and Blockers Using
      DiSBAC1(3) Membrane Potential Red Dye.
AB  - Fluorometric imaging plate reader membrane potential dye (FMP-Red-Dye) is a
      proprietary tool for basic discovery and high-throughput drug screening for G
      protein-coupled receptors and ion channels. We optimized and validated this
      potentiometric probe to assay functional modulators of heterologous expressed
      GABAA receptor (GABAAR) isoforms (synaptic alpha1beta3gamma2, extrasynaptic
      alpha4beta3delta, and beta3 homopentomers). High-resolution mass spectrometry
      identified FMP-Red-Dye as 5,5'-(1-propen-1-yl-3-ylidene)bis[1,3-dimethyl-2-thio
      barbituric acid]. GABAAR-expressing cells equilibrated with FMP-Red-Dye exhibited
      depolarized equilibrium membrane potentials compared with GABAAR-null cells. The
      channel blockers picrotoxin, fipronil, and tetramethylenedisulfotetramine, and
      the competitive antagonist bicuculline reduced fluorescence near the levels in
      GABAAR-null cells indicating that FMR-Red-Dye, a barbiturate derivative,
      activates GABAAR-mediated outward Cl- current in the absence of GABA. GABA caused
      concentration-dependent increases in fluorescence with rank order of potencies
      among GABAAR isoforms consistent with results from voltage-clamp experiments
      (EC50 values for alpha4beta3delta, alpha1beta3gamma2, and beta3 homopentamers
      were 6 +/- 1, 40 +/- 11, and >18 mM, respectively), whereas GABAAR-null cells
      were unresponsive. Neuroactive steroids (NAS) increased fluorescence of GABAAR
      expressing cells in the absence of GABA and demonstrated positive allosteric
      modulation in the presence of GABA, whereas benzodiazepines only exhibited
      positive allosteric modulator (PAM) activity. Of 20 NAS tested, allopregnanolone,
      (3alpha,5alpha,20E)-3-hydroxy-13,24-cyclo-18-norcholan-20-ene-21-carbonitrile,
      eltanolone, 5beta-pregnan-3alpha,21-diol-20-one, and ganaxolone showed the
      highest potency. The FMP-Red-Dye-based assay described here provides a sensitive
      and quantitative method of assessing the activity of GABAAR agonists,
      antagonists, and PAMs on diverse GABAAR isoforms. The assay has a wide range of
      applications, including screening for antiseizure agents and identifying channel
      blockers of interest to insecticide discovery or biosecurity.

PMID- 28428227
TI  - MECHANISMS IN ENDOCRINOLOGY: The multiple facets of GHRH/GH/IGF-I axis: lessons
      from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene
      mutation.
AB  - Twenty years ago, we described kindred of 105 individuals with isolated GH
      deficiency (IGHD) in Itabaianinha County, in northeast Brazil, carrying a
      homozygous mutation in the GH-releasing hormone receptor gene. These subjects
      exhibit markedly reduced GH responsiveness to stimulatory tests, and anterior
      pituitary hypoplasia. Serum concentrations of IGF-I, IGF binding protein type 3
      and the acid-labile subunit are markedly reduced, with a lesser reduction of IGF
      II. The most striking physical findings of these IGHD individuals are the
      proportionate short stature, doll facies, high-pitched voice and visceral obesity
      with reduced fat-free mass. There is neither microphallus, nor neonatal
      hypoglycemia. Puberty is delayed, menopause anticipated, but fertility is
      preserved in both genders. The reduction in bone sizes is not even, with mean
      standard deviation scores for height of -7.2, total maxillary length of -6.5,
      total facial height of -4.3 and cephalic perimeter of -2.7. In addition, the non
      osseous growth is not uniform, preserving some organs, like pancreas, liver,
      kidney, brain and eyes, and compromising others such as thyroid, heart, uterus
      and spleen. These subjects present higher prevalence of dizziness, mild high
      tones sensorineural hearing loss, reduction of vascular retinal branching points,
      increase of optic disk, genu valgum and increased systolic blood pressure.
      Biochemically, they have high low density lipoprotein cholesterol and C-reactive
      protein levels, but maintain increased insulin sensitivity, and do not show
      premature atherosclerosis. Finally, they have normal immune function, and normal
      longevity. This review details the findings and summarizes 20 years of clinical
      research carried out in this unique population.

PMID- 28428228
TI  - Postictal thoracocervicofacial purpura.

PMID- 28428229
TI  - Withdrawal of invasive ventilation in a patient with motor neurone disease and
      total locked-in syndrome.
AB  - Withdrawing invasive ventilation from a person with motor neurone disease who
      lacks the relevant mental capacity raises ethical issues such as the withdrawal
      of life-sustaining treatment and establishing best interests. There is little
      available information on providing optimal symptom management to these patients
      during the withdrawal process. We describe a man with motor neurone disease who
      also had total locked-in syndrome at the time of ventilation withdrawal, and we
      document the legal, ethical, emotional and symptom control issues encountered in
      supporting him.

PMID- 28428230
TI  - Hypodense artery sign in cerebral fat embolism.

PMID- 28428233
TI  - Efficacy in the margins of NHL with ibrutinib.

PMID- 28428231
TI  - Thresholds for Ambulatory Blood Pressure Among African Americans in the Jackson
      Heart Study.
AB  - BACKGROUND: Ambulatory blood pressure (BP) monitoring is the reference standard
      for out-of-clinic BP measurement. Thresholds for identifying ambulatory
      hypertension (daytime systolic BP [SBP]/diastolic BP [DBP] >=135/85 mm Hg, 24
      hour SBP/DBP >=130/80 mm Hg, and nighttime SBP/DBP >=120/70 mm Hg) have been
      derived from European, Asian, and South American populations. We determined BP
      thresholds for ambulatory hypertension in a US population-based sample of African
      American adults. METHODS: We analyzed data from the Jackson Heart Study, a
      population-based cohort study comprised exclusively of African American adults
      (n=5306). Analyses were restricted to 1016 participants who completed ambulatory
      BP monitoring at baseline in 2000 to 2004. Mean SBP and DBP levels were
      calculated for daytime (10:00 am-8:00 pm), 24-hour (all available readings), and
      nighttime (midnight-6:00 am) periods, separately. Daytime, 24-hour, and nighttime
      BP thresholds for ambulatory hypertension were identified using regression- and
      outcome-derived approaches. The composite of a cardiovascular disease or an all
      cause mortality event was used in the outcome-derived approach. For this latter
      approach, BP thresholds were identified only for SBP because clinic DBP was not
      associated with the outcome. Analyses were stratified by antihypertensive
      medication use. RESULTS: Among participants not taking antihypertensive
      medication, the regression-derived thresholds for daytime, 24-hour, and nighttime
      SBP/DBP corresponding to clinic SBP/DBP of 140/90 mm Hg were 134/85 mm Hg, 130/81
      mm Hg, and 123/73 mm Hg, respectively. The outcome-derived thresholds for
      daytime, 24-hour, and nighttime SBP corresponding to a clinic SBP >=140 mm Hg
      were 138 mm Hg, 134 mm Hg, and 129 mm Hg, respectively. Among participants taking
      antihypertensive medication, the regression-derived thresholds for daytime, 24
      hour, and nighttime SBP/DBP corresponding to clinic SBP/DBP of 140/90 mm Hg were
      135/85 mm Hg, 133/82 mm Hg, and 128/76 mm Hg, respectively. The corresponding
      outcome-derived thresholds for daytime, 24-hour, and nighttime SBP were 140 mm
      Hg, 137 mm Hg, and 133 mm Hg, respectively, among those taking antihypertensive
      medication. CONCLUSIONS: On the basis of the outcome-derived approach for SBP and
      regression-derived approach for DBP, the following definitions for daytime, 24
      hour, and nighttime hypertension corresponding to clinic SBP/DBP >=140/90 mm Hg
      are proposed for African American adults: daytime SBP/DBP >=140/85 mm Hg, 24-hour
      SBP/DBP >=135/80 mm Hg, and nighttime SBP/DBP >=130/75 mm Hg, respectively.

PMID- 28428234
TI  - Multiple myeloma cells sent "PAKing"!

PMID- 28428235
TI  - Anti-CD20-IL-21 fusokine: the tail wags the dog.

PMID- 28428236
TI  - I am SAMD9L: 7q regulator I am.

PMID- 28428237
TI  - Making thrombolysis safer in stroke.

PMID- 28428238
TI  - Complement and clot.

PMID- 28428239
TI  - MDS with isolated del(5q) and internuclear bridging.

PMID- 28428240
TI  - Risk of heart failure following Hodgkin lymphoma.

PMID- 28428241
TI  - WITHDRAWN: Heralds of parallel MS: Data-independent acquisition surpassing
      sequential identification of data dependent acquisition in proteomics.
AB  - This article has been withdrawn by the authors. This article did not comply with
      the editorial guidelines of MCP. Specifically, single peptide based protein
      identifications of 9-19% were included in the analysis and discussed in the
      results and conclusions. We wish to withdraw this article and resubmit a
      clarified, corrected manuscript for review.

PMID- 28428244
TI  - The role of social media around patient experience and engagement.

PMID- 28428242
TI  - Mapping the Synthetic Dosage Lethality Network of CDK1/CDC28.
AB  - Cdk1 (Cdc28 in yeast) is a cyclin-dependent kinase (CDK) essential for cell cycle
      progression and cell division in normal cells. However, CDK activity also
      underpins proliferation of tumor cells, making it a relevant study subject. While
      numerous targets and processes regulated by Cdc28 have been identified, the exact
      functions of Cdc28 are only partially understood. To further explore the
      functions of Cdc28, we systematically overexpressed ~4800 genes in wild-type (WT)
      cells and in cells with artificially reduced Cdc28 activity. This screen
      identified 366 genes that, when overexpressed, specifically compromised cell
      viability under conditions of reduced Cdc28 activity. Consistent with the crucial
      functions of Cdc28 in cell cycle regulation and chromosome metabolism, most of
      these genes have functions in the cell cycle, DNA replication, and transcription.
      However, a substantial number of genes control processes not directly associated
      with the cell cycle, indicating that Cdc28 may also regulate these processes.
      Finally, because the dataset was enriched for direct Cdc28 targets, the results
      from this screen will aid in identifying novel targets and process regulated by
      Cdc28.

PMID- 28428243
TI  - Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular
      Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles
      funestus Across Africa.
AB  - Pyrethroid resistance in malaria vector, An. funestus is increasingly reported
      across Africa, threatening the sustainability of pyrethroid-based control
      interventions, including long lasting insecticidal nets (LLINs). Managing this
      problem requires understanding of the molecular basis of the resistance from
      different regions of the continent, to establish whether it is being driven by a
      single or independent selective events. Here, using a genome-wide transcription
      profiling of pyrethroid resistant populations from southern (Malawi), East
      (Uganda), and West Africa (Benin), we investigated the molecular basis of
      resistance, revealing strong differences between the different African regions.
      The duplicated cytochrome P450 genes (CYP6P9a and CYP6P9b) which were highly
      overexpressed in southern Africa are not the most upregulated in other regions,
      where other genes are more overexpressed, including GSTe2 in West (Benin) and
      CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and
      CYP6P9b in Uganda in contrast to southern Africa further supports the limited
      role of these genes outside southern Africa. However, other genes such as the
      P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here,
      CYP9J11 is functionally characterized and shown to confer resistance to
      pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The
      consistent overexpression of GSTe2 in Benin is coupled with a role of allelic
      variation at this gene as GAL4-UAS transgenic expression in Drosophila flies
      showed that the resistant 119F allele is highly efficient in conferring both DDT
      and permethrin resistance than the L119. The heterogeneity in the molecular basis
      of resistance and cross-resistance to insecticides in An. funestus populations
      throughout sub-Saharan African should be taken into account in designing
      resistance management strategies.

PMID- 28428245
TI  - Thematic analysis of US stakeholder views on the influence of labour nurses' care
      on birth outcomes.
AB  - BACKGROUND: Childbirth is a leading reason for hospital admission in the USA, and
      most labour care is provided by registered nurses under physician or midwife
      supervision in a nurse-managed care model. Yet, there are no validated nurse
      sensitive quality measures for maternity care. We aimed to engage primary
      stakeholders of maternity care in identifying the aspects of nursing care during
      labour and birth they believe influence birth outcomes, and how these aspects of
      care might be measured. METHODS: This qualitative study used 15 focus groups to
      explore perceptions of 73 nurses, 23 new mothers and 9 physicians regarding
      important aspects of care. Transcripts were analysed thematically. Participants
      in the final six focus groups were also asked whether or not they thought each of
      five existing perinatal quality measures were nurse-sensitive. RESULTS: Nurses,
      new mothers and physicians identified nurses' support of and advocacy for women
      as important to birth outcomes. Support and advocacy actions included keeping
      women and their family members informed, being present with women, setting the
      emotional tone, knowing and advocating for women's wishes and avoiding caesarean
      birth. Mothers and nurses took technical aspects of care for granted, whereas
      physicians discussed this more explicitly, noting that nurses were their 'eyes
      and ears' during labour. Participants endorsed caesarean rates and breastfeeding
      rates as likely to be nurse-sensitive. CONCLUSIONS: Stakeholder values support
      inclusion of maternity nursing care quality measures related to emotional support
      and providing information in addition to physical support and clinical aspects of
      care. Care models that ensure labour nurses have sufficient time and resources to
      engage in the supportive relationships that women value might contribute to
      better health outcomes and improved patient experience.

PMID- 28428246
TI  - Key features of an Hsp70 chaperone allosteric landscape revealed by ion-mobility
      native mass spectrometry and double electron-electron resonance.
AB  - Proteins are dynamic entities that populate conformational ensembles, and most
      functions of proteins depend on their dynamic character. Allostery, in
      particular, relies on ligand-modulated shifts in these conformational ensembles.
      Hsp70s are allosteric molecular chaperones with conformational landscapes that
      involve large rearrangements of their two domains (viz. the nucleotide-binding
      domain and substrate-binding domain) in response to adenine nucleotides and
      substrates. However, it remains unclear how the Hsp70 conformational ensemble is
      populated at each point of the allosteric cycle and how ligands control these
      populations. We have mapped the conformational species present under different
      ligand-binding conditions throughout the allosteric cycle of the Escherichia coli
      Hsp70 DnaK by two complementary methods, ion-mobility mass spectrometry and
      double electron-electron resonance. Our results obtained under biologically
      relevant ligand-bound conditions confirm the current picture derived from NMR and
      crystallographic data of domain docking upon ATP binding and undocking in
      response to ADP and substrate. Additionally, we find that the helical lid of DnaK
      is a highly dynamic unit of the structure in all ligand-bound states.
      Importantly, we demonstrate that DnaK populates a partially docked state in the
      presence of ATP and substrate and that this state represents an energy minimum on
      the DnaK allosteric landscape. Because Hsp70s are emerging as potential drug
      targets for many diseases, fully mapping an allosteric landscape of a molecular
      chaperone like DnaK will facilitate the development of small molecules that
      modulate Hsp70 function via allosteric mechanisms.

PMID- 28428247
TI  - Induction of cell death and gain-of-function properties of connexin26 mutants
      predict severity of skin disorders and hearing loss.
AB  - Connexin26 (Cx26) is a gap junction protein that oligomerizes in the cell to form
      hexameric transmembrane channels called connexons. Cell surface connexons dock
      between adjacent cells to allow for gap junctional intercellular communication.
      Numerous autosomal dominant mutations in the Cx26-encoding GJB2 gene lead to many
      skin disorders and sensorineural hearing loss. Although some insights have been
      gained into the pathogenesis of these diseases, it is not fully understood how
      distinct GJB2 mutations result in hearing loss alone or in skin pathologies with
      comorbid hearing loss. Here we investigated five autosomal dominant Cx26 mutants
      (N14K, D50N, N54K, M163V, and S183F) linked to various syndromic or nonsyndromic
      diseases to uncover the molecular mechanisms underpinning these disease links. We
      demonstrated that when gap junction-deficient HeLa cells expressed the N14K and
      D50N mutants, they undergo cell death. The N54K mutant was retained primarily
      within intracellular compartments and displayed dominant or transdominant
      properties on wild-type Cx26 and coexpressed Cx30 and Cx43. The S183F mutant
      formed some gap junction plaques but was largely retained within the cell and
      exhibited only a mild transdominant reduction in gap junction communication when
      co-expressed with Cx30. The M163V mutant, which causes only hearing loss,
      exhibited impaired gap junction function and showed no transdominant
      interactions. These findings suggest that Cx26 mutants that promote cell death or
      exert transdominant effects on other connexins in keratinocytes will lead to skin
      diseases and hearing loss, whereas mutants having reduced channel function but
      exhibiting no aberrant effects on coexpressed connexins cause only hearing loss.
      Moreover, cell death-inducing GJB2 mutations lead to more severe syndromic
      disease.

PMID- 28428248
TI  - New insights into the tetraspanin Tspan5 using novel monoclonal antibodies.
AB  - Tspan5 is a member of a subgroup of tetraspanins referred to as TspanC8. These
      tetraspanins directly interact with the metalloprotease ADAM10, regulate its exit
      from the endoplasmic reticulum and subsequent trafficking, and differentially
      regulate its ability to cleave various substrates and activate Notch signaling.
      The study of Tspan5 has been limited by the lack of good antibodies. This study
      provides new insights into Tspan5 using new monoclonal antibodies (mAbs),
      including two mAbs recognizing both Tspan5 and the highly similar tetraspanin
      Tspan17. Using these mAbs, we show that endogenous Tspan5 associates with ADAM10
      in human cell lines and in mouse tissues where it is the most abundant, such as
      the brain, the lung, the kidney, or the intestine. We also uncover two TspanC8
      specific motifs in the large extracellular domain of Tspan5 that are important
      for ADAM10 interaction and exit from the endoplasmic reticulum. One of the anti
      Tspan5 mAbs does not recognize Tspan5 associated with ADAM10, providing a
      convenient way to measure the fraction of Tspan5 not associated with ADAM10. This
      fraction is minor in the cell lines tested, and it increases upon transfection of
      cells with TspanC8 tetraspanins such as Tspan15 or Tspan33 that inhibit Notch
      signaling. Finally, two antibodies inhibit ligand-induced Notch signaling, and
      this effect is stronger in cells depleted of the TspanC8 tetraspanin Tspan14,
      further indicating that Tspan5 and Tspan14 can compensate for each other in Notch
      signaling.

PMID- 28428250
TI  - Functional roles of globin proteins in hypoxia-tolerant ectothermic vertebrates.
AB  - Globins are heme-containing proteins ubiquitously expressed in vertebrates, where
      they serve a broad range of biological functions, directly or indirectly related
      to the tight control of oxygen levels and its toxic products in vivo. Perhaps the
      most investigated of all proteins, hemoglobin and myoglobin are primarily
      involved in oxygen transport and storage, but also in facilitating arterial
      vasodilation, suppressing mitochondrial respiration, and preventing tissue
      oxidative damage via accessory redox enzymatic activities during hypoxia. By
      contrast, the more recently discovered neuroglobin and cytoglobin do not seem to
      function as reversible oxygen carriers and are instead involved in redox
      activities, although their exact biological roles remain to be clarified. In this
      context, hypoxia-tolerant ectotherms, such as freshwater turtles and members of
      the carp family that survive winter in extreme hypoxia, have proven as excellent
      models to appreciate the diversity of biological functions of globin proteins.
      Unraveling physiological roles of globin proteins in these extreme animals will
      clarify an important part of the adaptive mechanisms for surviving extreme
      fluctuations of oxygen availability that are prohibitive to mammals.

PMID- 28428251
TI  - Loopomics: a new functional approach to life.

PMID- 28428249
TI  - Crystal structure and redox properties of a novel cyanobacterial heme protein
      with a His/Cys heme axial ligation and a Per-Arnt-Sim (PAS)-like domain.
AB  - Photosystem II catalyzes light-induced water oxidation leading to the generation
      of dioxygen indispensable for sustaining aerobic life on Earth. The Photosystem
      II reaction center is composed of D1 and D2 proteins encoded by psbA and psbD
      genes, respectively. In cyanobacteria, different psbA genes are present in the
      genome. The thermophilic cyanobacterium Thermosynechococcus elongatus contains
      three psbA genes: psbA1, psbA2, and psbA3, and a new c-type heme protein,
      Tll0287, was found to be expressed in a strain expressing the psbA2 gene only,
      but the structure and function of Tll0287 are unknown. Here we solved the crystal
      structure of Tll0287 at a 2.0 A resolution. The overall structure of Tll0287 was
      found to be similar to some kinases and sensor proteins with a Per-Arnt-Sim-like
      domain rather than to other c-type cytochromes. The fifth and sixth axial ligands
      for the heme were Cys and His, instead of the His/Met or His/His ligand pairs
      observed for most of the c-type hemes. The redox potential, E1/2, of Tll0287 was 
      255 +/- 20 mV versus normal hydrogen electrode at pH values above 7.5. Below this
      pH value, the E1/2 increased by ~57 mV/pH unit at 15  degrees C, suggesting the
      involvement of a protonatable group with a pKred = 7.2 +/- 0.3. Possible
      functions of Tll0287 as a redox sensor under microaerobic conditions or a
      cytochrome subunit of an H2S-oxidizing system are discussed in view of the
      environmental conditions in which psbA2 is expressed, as well as phylogenetic
      analysis, structural, and sequence homologies.

PMID- 28428252
TI  - Low-frequency blood pressure oscillations and inotrope treatment failure in
      premature infants.
AB  - The underlying mechanism as to why some hypotensive preterm infants do not
      respond to inotropic medications remains unclear. For these infants, we
      hypothesize that impaired vasomotor function is a significant factor and is
      manifested through a decrease in low-frequency blood pressure variability across
      regulatory components of vascular tone. Infants born <=28 wk estimated
      gestational age underwent prospective recording of mean arterial blood pressure
      for 72 h after birth. After error correction, root-mean-square spectral power was
      calculated for each valid 10-min data frame across each of four frequency bands
      (B1, 0.005-0.0095 Hz; B2, 0.0095-0.02 Hz; B3, 0.02-0.06 Hz; and B4, 0.06-0.16)
      corresponding to different components of vasomotion control. Forty infants
      (twenty-nine normotensive control and eleven inotrope-exposed) were included with
      a mean +/- SD estimated gestational age of 25.2 +/- 1.6 wk and birth weight 790
      +/- 211 g. 9.7/11.8 Million (82%) data points were error-free and used for
      analysis. Spectral power across all frequency bands increased with time, although
      the magnitude was 20% less in the inotrope-exposed infants. A statistically
      significant increase in spectral power in response to inotrope initiation was
      noted across all frequency bands. Infants with robust blood pressure response to
      inotropes had a greater increase compared with those who had limited or no blood
      pressure response. In this study, hypotensive infants who require inotropes have
      decreased low-frequency variability at baseline compared with normotensive
      infants, which increases after inotrope initiation. Low-frequency spectral power
      does not change for those with inotrope treatment failure, suggesting
      dysfunctional regulation of vascular tone as a potential mechanism of treatment
      failure.NEW & NOTEWORTHY In this study, we examine patterns of low-frequency
      oscillations in blood pressure variability across regulatory components of
      vascular tone in normotensive and hypotensive infants exposed to inotropic
      medications. We found that hypotensive infants who require inotropes have
      decreased low-frequency variability at baseline, which increases after inotrope
      initiation. Low-frequency spectral power does not change for those with inotrope
      treatment failure, suggesting dysfunctional regulation of vascular tone as a
      potential mechanism of treatment failure.

PMID- 28428253
TI  - Twitchin kinase inhibits muscle activity.
AB  - Muscle sarcomeres contain giant polypeptides composed of multiple immunoglobulin
      and fibronectin domains and one or two protein kinase domains. Although binding
      partners for a number of this family's kinase domains have been identified, the
      catalytic necessity of these kinase domains remains unknown. In addition, various
      members of this kinase family are suspected pseudokinases with no or little
      activity. Here we address catalytic necessity for the first time, using the
      prototypic invertebrate representative twitchin (UNC-22) from Caenorhabditis
      elegans In in vitro experiments, change of a conserved lysine (K) that is
      involved in ATP coordination to alanine (A) resulted in elimination of kinase
      activity without affecting the overall structure of the kinase domain. The same
      mutation, unc-22(sf21), was generated in the endogenous twitchin gene. The unc
      22(sf21) worms have well-organized sarcomeres. However, unc-22(sf21) mutants move
      faster than wild-type worms and, by optogenetic experiments, contract more. Wild
      type nematodes exhibited greater competitive fitness than unc-22(sf21) mutants.
      Thus the catalytic activity of twitchin kinase has a role in vivo, where it
      inhibits muscle activity and is likely maintained by selection.

PMID- 28428254
TI  - A novel physiological role for ARF1 in the formation of bidirectional tubules
      from the Golgi.
AB  - Capitalizing on CRISPR/Cas9 gene-editing techniques and super-resolution
      nanoscopy, we explore the role of the small GTPase ARF1 in mediating transport
      steps at the Golgi. Besides its well-established role in generating COPI
      vesicles, we find that ARF1 is also involved in the formation of long (~3 um),
      thin (~110 nm diameter) tubular carriers. The anterograde and retrograde tubular
      carriers are both largely free of the classical Golgi coat proteins coatomer
      (COPI) and clathrin. Instead, they contain ARF1 along their entire length at a
      density estimated to be in the range of close packing. Experiments using a mutant
      form of ARF1 affecting GTP hydrolysis suggest that ARF1[GTP] is functionally
      required for the tubules to form. Dynamic confocal and stimulated emission
      depletion imaging shows that ARF1-rich tubular compartments fall into two
      distinct classes containing 1) anterograde cargoes and clathrin clusters or 2)
      retrograde cargoes and coatomer clusters.

PMID- 28428255
TI  - Nucleosome-nucleosome interactions via histone tails and linker DNA regulate
      nuclear rigidity.
AB  - Cells, as well as the nuclei inside them, experience significant mechanical
      stress in diverse biological processes, including contraction, migration, and
      adhesion. The structural stability of nuclei must therefore be maintained in
      order to protect genome integrity. Despite extensive knowledge on nuclear
      architecture and components, however, the underlying physical and molecular
      mechanisms remain largely unknown. We address this by subjecting isolated human
      cell nuclei to microneedle-based quantitative micromanipulation with a series of
      biochemical perturbations of the chromatin. We find that the mechanical rigidity
      of nuclei depends on the continuity of the nucleosomal fiber and interactions
      between nucleosomes. Disrupting these chromatin features by varying cation
      concentration, acetylating histone tails, or digesting linker DNA results in loss
      of nuclear rigidity. In contrast, the levels of key chromatin assembly factors,
      including cohesin, condensin II, and CTCF, and a major nuclear envelope protein,
      lamin, are unaffected. Together with in situ evidence using living cells and a
      simple mechanical model, our findings reveal a chromatin-based regulation of the
      nuclear mechanical response and provide insight into the significance of local
      and global chromatin structures, such as those associated with interdigitated or
      melted nucleosomal fibers.

PMID- 28428256
TI  - Regulation of lung endothelial permeability and inflammatory responses by
      prostaglandin A2: role of EP4 receptor.
AB  - The role of prostaglandin A2 (PGA2) in modulation of vascular endothelial
      function is unknown. We investigated effects of PGA2 on pulmonary endothelial
      cell (EC) permeability and inflammatory activation and identified a receptor
      mediating these effects. PGA2 enhanced the EC barrier and protected against
      barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory
      bacterial wall lipopolysaccharide (LPS). Receptor screening using pharmacological
      and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor. EP4
      mediated barrier-protective effects of PGA2 by activating Rap1/Rac1 GTPase and
      protein kinase A targets at cell adhesions and cytoskeleton: VE-cadherin, p120
      catenin, ZO-1, cortactin, and VASP. PGA2 also suppressed LPS-induced inflammatory
      signaling by inhibiting the NFkappaB pathway and expression of EC adhesion
      molecules ICAM1 and VCAM1. These effects were abolished by pharmacological or
      molecular inhibition of EP4. In vivo, PGA2 was protective in two distinct models
      of acute lung injury (ALI): LPS-induced inflammatory injury and two-hit ALI
      caused by suboptimal mechanical ventilation and injection of thrombin receptor
      activating peptide. These protective effects were abolished in mice with
      endothelial-specific EP4 knockout. The results suggest a novel role for the PGA2
      EP4 axis in vascular EC protection that is critical for improvement of
      pathological states associated with increased vascular leakage and inflammation.

PMID- 28428257
TI  - The size-speed-force relationship governs migratory cell response to tumorigenic
      factors.
AB  - Tumor development progresses through a complex path of biomechanical changes
      leading first to cell growth and contraction and then cell deadhesion,
      scattering, and invasion. Tumorigenic factors may act specifically on one of
      these steps or have a wider spectrum of actions, leading to a variety of effects
      and thus sometimes to apparent contradictory outcomes. Here we used
      micropatterned lines of collagen type I/fibronectin on deformable surfaces to
      standardize cell behavior and measure simultaneously cell size, speed of motion
      and magnitude of the associated traction forces at the level of a single cell. We
      analyzed and compared the normal human breast cell line MCF10A in control
      conditions and in response to various tumorigenic factors. In all conditions, a
      wide range of biomechanical properties was identified. Despite this
      heterogeneity, normal and transformed motile cells followed a common trend
      whereby size and contractile forces were negatively correlated with cell speed.
      Some tumorigenic factors, such as activation of ErbB2 or loss of the betasubunit
      of casein kinase 2, shifted the whole population toward a faster speed and lower
      contractility state. Treatment with transforming growth factor beta induced some
      cells to adopt opposing behaviors such as extremely high versus extremely low
      contractility. Thus tumor transformation amplified preexisting population
      heterogeneity and led some cells to exhibit biomechanical properties that were
      more extreme than those observed with normal cells.

PMID- 28428258
TI  - Deletion of inositol-requiring enzyme-1alpha in podocytes disrupts glomerular
      capillary integrity and autophagy.
AB  - Inositol-requiring enzyme-1alpha (IRE1alpha) is an endoplasmic reticulum (ER)
      transmembrane endoribonuclease kinase that plays an essential function in
      extraembryonic tissues during normal development and is activated during ER
      stress. To address the functional role of IRE1alpha in glomerular podocytes, we
      produced podocyte-specific IRE1alpha-deletion mice. In male mice, deletion of
      IRE1alpha in podocytes resulted in albuminuria beginning at 5 mo of age and
      worsening with time. Electron microscopy revealed focal podocyte foot-process
      effacement in 9-mo-old male IRE1alpha-deletion mice, as well as microvillous
      transformation of podocyte plasma membranes. Compared with control, glomerular
      cross-sectional and capillary lumenal areas were greater in deletion mice, and
      there was relative podocyte depletion. Levels of microtubule-associated protein
      1A/1B-light chain 3 (LC3)-II expression and c-Jun N-terminal kinase-1
      phosphorylation were decreased in IRE1alpha-deletion glomeruli, in keeping with
      reduced autophagy. Deletion of IRE1alpha exacerbated glomerular injury in anti
      glomerular basement membrane nephritis. In cell culture, IRE1alpha dominant
      negative mutants reduced the physiological (basal) accumulation of LC3B-II and
      the size of autophagic vacuoles but did not affect ER-associated degradation.
      Thus IRE1alpha is essential for maintaining podocyte and glomerular integrity as
      mice age and in glomerulonephritis. The mechanism is related, at least in part,
      to the maintenance of autophagy in podocytes.

PMID- 28428259
TI  - RABL2 interacts with the intraflagellar transport-B complex and CEP19 and
      participates in ciliary assembly.
AB  - Proteins localized to the basal body and the centrosome play crucial roles in
      ciliary assembly and function. Although RABL2 and CEP19 are conserved in ciliated
      organisms and have been implicated in ciliary/flagellar functions, their roles
      are poorly understood. Here we show that RABL2 interacts with CEP19 and is
      recruited to the mother centriole and basal body in a CEP19-dependent manner and
      that CEP19 is recruited to the centriole probably via its binding to the
      centrosomal protein FGFR1OP. Disruption of the RABL2 gene in Chlamydomonas
      reinhardtii results in the nonflagellated phenotype, suggesting a crucial role of
      RABL2 in ciliary/flagellar assembly. We also show that RABL2 interacts, in its
      GTP-bound state, with the intraflagellar transport (IFT)-B complex via the IFT74
      IFT81 heterodimer and that the interaction is disrupted by a mutation found in
      male infertile mice (Mot mice) with a sperm flagella motility defect.
      Intriguingly, RABL2 binds to CEP19 and the IFT74-IFT81 heterodimer in a mutually
      exclusive manner. Furthermore, exogenous expression of the GDP-locked or Mot-type
      RABL2 mutant in human cells results in mild defects in ciliary assembly. These
      results indicate that RABL2 localized to the basal body plays crucial roles in
      ciliary/flagellar assembly via its interaction with the IFT-B complex.

PMID- 28428261
TI  - EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3
      and the BAF chromatin remodeling complex.
AB  - The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of
      brown adipocyte commitment and terminal differentiation. However, the mechanisms
      by which EBF2 regulates chromatin to activate brown fat-specific genes in
      adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed
      by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and
      regulates the activity of lineage-specific enhancers. Mechanistically, EBF2
      physically interacts with the chromatin remodeler BRG1 and the BAF chromatin
      remodeling complex in brown adipocytes. We identified the histone reader protein
      DPF3 as a brown fat-selective component of the BAF complex that was required for
      brown fat gene programming and mitochondrial function. Loss of DPF3 in brown
      adipocytes reduced chromatin accessibility at EBF2-bound enhancers and led to a
      decrease in basal and catecholamine-stimulated expression of brown fat-selective
      genes. Notably, Dpf3 is a direct transcriptional target of EBF2 in brown
      adipocytes, thereby establishing a regulatory module through which EBF2 activates
      and also recruits DPF3-anchored BAF complexes to chromatin. Together, these
      results reveal a novel mechanism by which EBF2 cooperates with a tissue-specific
      chromatin remodeling complex to activate brown fat identity genes.

PMID- 28428262
TI  - Uncoupling neurogenic gene networks in the Drosophila embryo.
AB  - The EGF signaling pathway specifies neuronal identities in the Drosophila embryo
      by regulating developmental patterning genes such as intermediate neuroblasts
      defective (ind). EGFR is activated in the ventral midline and neurogenic ectoderm
      by the Spitz ligand, which is processed by the Rhomboid protease. CRISPR/Cas9 was
      used to delete defined rhomboid enhancers mediating expression at each site of
      Spitz processing. Surprisingly, the neurogenic ectoderm, not the ventral midline,
      was found to be the dominant source of EGF patterning activity. We suggest that
      Drosophila is undergoing an evolutionary transition in central nervous system
      (CNS)-organizing activity from the ventral midline to the neurogenic ectoderm.

PMID- 28428263
TI  - Different requirements of functional telomeres in neural stem cells and
      terminally differentiated neurons.
AB  - Telomeres have been studied extensively in peripheral tissues, but their
      relevance in the nervous system remains poorly understood. Here, we examine the
      roles of telomeres at distinct stages of murine brain development by using
      lineage-specific genetic ablation of TRF2, an essential component of the
      shelterin complex that protects chromosome ends from the DNA damage response
      machinery. We found that functional telomeres are required for embryonic and
      adult neurogenesis, but their uncapping has surprisingly no detectable
      consequences on terminally differentiated neurons. Conditional knockout of TRF2
      in post-mitotic immature neurons had virtually no detectable effect on circuit
      assembly, neuronal gene expression, and the behavior of adult animals despite
      triggering massive end-to-end chromosome fusions across the brain. These results
      suggest that telomeres are dispensable in terminally differentiated neurons and
      provide mechanistic insight into cognitive abnormalities associated with aberrant
      telomere length in humans.

PMID- 28428264
TI  - CB1 cannabinoid receptor drives oocyte maturation and embryo development via
      PI3K/Akt and MAPK pathways.
AB  - Endocannabinoids have been recognized as mediators of practically all
      reproductive events in mammals. However, little is known about the role of this
      system in oocyte maturation. In a mouse model, we observed that activation of
      cannabinoid receptor 1 (CB1) during in vitro oocyte maturation modulated the
      phosphorylation status of Akt and ERK1/2 and enhanced the subsequent embryo
      production. In the absence of CB1, in vivo oocyte maturation was impaired and
      embryo development delayed. Cannabinoid receptor 2 (CB2) was unable to rescue
      these effects. Finally, we confirmed abnormal oocyte maturation rather than
      impaired embryonic transport through the oviduct in CB1 knockouts. Our data
      suggest that cannabinoid agonists may be useful in vitro maturation supplements.
      For in vitro fertilization patients intolerant to gonadotropins, this could be a
      promising and only option.-Lopez-Cardona, A. P., Perez-Cerezales, S., Fernandez
      Gonzalez, R., Laguna-Barraza, R., Pericuesta, E., Agirregoitia, N., Gutierrez
      Adan, A., Agirregoitia, E. CB1 cannabinoid receptor drives oocyte maturation and
      embryo development via PI3K/Akt and MAPK pathways.

PMID- 28428265
TI  - Inhibition of thyroid hormone receptor locally in the retina is a therapeutic
      strategy for retinal degeneration.
AB  - Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and
      metabolism. Recent studies have implicated TH signaling in cone photoreceptor
      viability. Using mouse models of retinal degeneration, we demonstrated that
      antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to
      suppress cellular tri-iodothyronine (T3) production or increase T3 degradation
      preserves cones. In this work, we investigated the effectiveness of inhibition of
      the TH receptor (TR). Two genes, THRA and THRB, encode TRs; THRB2 has been
      associated with cone viability. Using TR antagonists and Thrb2 deletion, we
      examined the effects of TR inhibition. Systemic and ocular treatment with the TR
      antagonists NH-3 and 1-850 increased cone density by 30-40% in the Rpe65-/- mouse
      model of Leber congenital amaurosis and reduced the number of TUNEL+ cells. Cone
      survival was significantly improved in Rpe65-/- and Cpfl1 (a model of
      achromatopsia with Pde6c defect) mice with Thrb2 deletion. Ventral cone density
      in Cpfl1/Thrb2-/- and Rpe65-/- /Thrb2-/- mice was increased by 1- to 4-fold,
      compared with age-matched controls. Moreover, the expression levels of TR were
      significantly higher in the cone-degeneration retinas, suggesting locally
      elevated TR signaling. This work shows that the effects of antithyroid treatment
      or targeting DIOs were likely mediated by TRs and that suppressing TR protects
      cones. Our findings support the view that inhibition of TR locally in the retina
      is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F.,
      Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding,
      X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a
      therapeutic strategy for retinal degeneration.

PMID- 28428267
TI  - Association of NF-kappaB polymorphisms with clinical outcome of non-medullary
      thyroid carcinoma.
AB  - The NF-kappaB inflammatory pathway plays a major role in cancer development and
      clinical progression. Activation of NF-kappaB signaling is promoted by NFKB1 and
      inhibited by NFKBIA. The present study aimed to determine the relevance of NFKB1
      rs4648068 and NFKBIA rs2233406 genetic variants for non-medullary thyroid cancer
      (NMTC) susceptibility, progression and clinical outcome. This case-control and
      cohort study consists of a Romanian discovery cohort (157 patients and 258
      controls) and a Dutch validation cohort (138 patients and 188 controls). In
      addition, patient cohorts were analyzed further for the association of genetic
      variants with clinical parameters. Functional studies were performed on human
      peripheral blood mononuclear cells. No associations were observed between the
      studied genetic variants and TC susceptibility. Although no statistically
      significant associations with clinical parameters were observed for NFKB1
      rs4648068, the heterozygous genotype of NFKBIA rs2233406 was correlated with
      decreased radioactive iodide sensitivity requiring higher cumulative dosages to
      achieve clinical response. These findings were discovered in the Romanian cohort
      (P < 0.001) and confirmed in the Dutch cohort (P = 0.01). Functional studies
      revealed that this NFKBIA rs2233406 genotype was associated with elevated TLR4
      mediated IL-1beta production. In conclusion, genetic variation in NFKBIA, an
      inhibitor of NF-kappaB signaling, is associated with clinical response to RAI
      therapy and with increased production of the pro-inflammatory cytokine IL-1beta,
      providing a potential mechanism for the observed clinical associations. These
      data suggest that NF-kappaB signaling is involved in NMTC pathogenesis and that
      the inflammatory tumor microenvironment could contribute to RAI resistance.

PMID- 28428266
TI  - KCa1.1 channels regulate beta1-integrin function and cell adhesion in rheumatoid
      arthritis fibroblast-like synoviocytes.
AB  - Large-conductance calcium-activated potassium channel (KCa1.1; BK, Slo1, MaxiK,
      KCNMA1) is the predominant potassium channel expressed at the plasma membrane of
      rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) isolated from the
      synovium of patients with RA. It is a critical regulator of RA-FLS migration and
      invasion and therefore represents an attractive target for the therapy of RA.
      However, the molecular mechanisms by which KCa1.1 regulates RA-FLS invasiveness
      have remained largely unknown. Here, we demonstrate that KCa1.1 regulates RA-FLS
      adhesion through controlling the plasma membrane expression and activation of
      beta1 integrins, but not alpha4, alpha5, or alpha6 integrins. Blocking KCa1.1
      disturbs calcium homeostasis, leading to the sustained phosphorylation of Akt and
      the recruitment of talin to beta1 integrins. Interestingly, the pore-forming
      alpha subunit of KCa1.1 coimmunoprecipitates with beta1 integrins, suggesting
      that this physical association underlies the functional interaction between these
      molecules. Together, these data outline a new signaling mechanism by which KCa1.1
      regulates beta1-integrin function and therefore invasiveness of RA-FLSs.-Tanner,
      M. R., Pennington, M. W., Laragione, T., Gulko, P. S., Beeton, C. KCa1.1 channels
      regulate beta1-integrin function and cell adhesion in rheumatoid arthritis
      fibroblast-like synoviocytes.

PMID- 28428268
TI  - Salvage use of allogeneic hematopoietic stem cell transplantation after reduced
      intensity conditioning from unrelated donors in multiple myeloma. A study by the
      Plasma Cell Disorders subcommittee of the European Group for Blood and Marrow
      Transplant Chronic Malignancies Working Party.

PMID- 28428269
TI  - Low frequency mutations in ribosomal proteins RPL10 and RPL5 in multiple myeloma.

PMID- 28428271
TI  - Master Transcriptional Regulators in Cancer: Discovery via Reverse Engineering
      Approaches and Subsequent Validation.
AB  - Reverse engineering of transcriptional networks using gene expression data
      enables identification of genes that underpin the development and progression of
      different cancers. Methods to this end have been available for over a decade and,
      with a critical mass of transcriptomic data in the oncology arena having been
      reached, they are ever more applicable. Extensive and complex networks can be
      distilled into a small set of key master transcriptional regulators (MTR), genes
      that are very highly connected and have been shown to be involved in processes of
      known importance in disease. Interpreting and validating the results of
      standardized bioinformatic methods is of crucial importance in determining the
      inherent value of MTRs. In this review, we briefly describe how MTRs are
      identified and focus on providing an overview of how MTRs can and have been
      validated for use in clinical decision making in malignant diseases, along with
      serving as tractable therapeutic targets. Cancer Res; 77(9); 2186-90. (c)2017
      AACR.

PMID- 28428270
TI  - Mutations in the adaptor-binding domain and associated linker region of p110delta
      cause Activated PI3K-delta Syndrome 1 (APDS1).

PMID- 28428272
TI  - HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis
      Polyposis and Colorectal Carcinogenesis.
AB  - HuR is an RNA-binding protein implicated in immune homeostasis and various
      cancers, including colorectal cancer. HuR binding to AU-rich elements within the
      3' untranslated region of mRNAs encoding oncogenes, growth factors, and various
      cytokines leads message stability and translation. In this study, we evaluated
      HuR as a small-molecule target for preventing colorectal cancer in high-risk
      groups such as those with familial adenomatosis polyposis (FAP) or inflammatory
      bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased
      in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and
      colorectal cancer, but not in patients with IBD-dysplasia. Intraperitoneal
      injection of the HuR small-molecule inhibitor MS-444 in AOM/DSS mice, a model of
      IBD and inflammatory colon cancer, augmented DSS-induced weight loss and
      increased tumor multiplicity, size, and invasiveness. MS-444 treatment also
      abrogated tumor cell apoptosis and depleted tumor-associated eosinophils,
      accompanied by a decrease in IL18 and eotaxin-1. In contrast, HuR inhibition in
      APCMin mice, a model of FAP and colon cancer, diminished the number of small
      intestinal tumors generated. In this setting, fecal microbiota, evaluated by 16S
      rRNA gene amplicon sequencing, shifted to a state of reduced bacterial diversity,
      with an increased representation of Prevotella, Akkermansia, and Lachnospiraceae
      Taken together, our results indicate that HuR activation is an early event in FAP
      adenoma but is not present in IBD-dysplasia. Furthermore, our results offer a
      preclinical proof of concept for HuR inhibition as an effective means of FAP
      chemoprevention, with caution advised in the setting of IBD. Cancer Res; 77(9);
      2424-38. (c)2017 AACR.

PMID- 28428273
TI  - Assessing Prostate Cancer Aggressiveness with Hyperpolarized Dual-Agent 3D
      Dynamic Imaging of Metabolism and Perfusion.
AB  - New magnetic resonance (MR) molecular imaging techniques offer the potential for
      noninvasive, simultaneous quantification of metabolic and perfusion parameters in
      tumors. This study applied a three-dimensional dynamic dual-agent hyperpolarized
      13C magnetic resonance spectroscopic imaging approach with 13C-pyruvate and 13C
      urea to investigate differences in perfusion and metabolism between low- and high
      grade tumors in the transgenic adenocarcinoma of mouse prostate (TRAMP)
      transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1
      relaxation and RF excitation and modeled to provide quantitative measures of
      pyruvate to lactate flux (kPL ) and urea perfusion (urea AUC) that correlated
      with TRAMP tumor histologic grade. kPL values were relatively higher for high
      grade TRAMP tumors. The increase in kPL flux correlated significantly with higher
      lactate dehydrogenase activity and mRNA expression of Ldha, Mct1, and Mct4 as
      well as with more proliferative disease. There was a significant reduction in
      perfusion in high-grade tumors that associated with increased hypoxia and mRNA
      expression of Hif1alpha and Vegf and increased ktrans , attributed to increased
      blood vessel permeability. In 90% of the high-grade TRAMP tumors, a mismatch in
      perfusion and metabolism measurements was observed, with low perfusion being
      associated with increased kPL This perfusion-metabolism mismatch was also
      associated with metastasis. The molecular imaging approach we developed could be
      translated to investigate these imaging biomarkers for their diagnostic and
      prognostic power in future prostate cancer clinical trials. Cancer Res; 77(12);
      3207-16. (c)2017 AACR.

PMID- 28428274
TI  - EGFR Mediates Responses to Small-Molecule Drugs Targeting Oncogenic Fusion
      Kinases.
AB  - Oncogenic kinase fusions of ALK, ROS1, RET, and NTRK1 act as drivers in human
      lung and other cancers. Residual tumor burden following treatment of ALK or ROS1+
      lung cancer patients with oncogene-targeted therapy ultimately enables the
      emergence of drug-resistant clones, limiting the long-term effectiveness of these
      therapies. To determine the signaling mechanisms underlying incomplete tumor cell
      killing in oncogene-addicted cancer cells, we investigated the role of EGFR
      signaling in drug-naive cancer cells harboring these oncogene fusions. We defined
      three distinct roles for EGFR in the response to oncogene-specific therapies.
      First, EGF-mediated activation of EGFR blunted fusion kinase inhibitor binding
      and restored fusion kinase signaling complexes. Second, fusion kinase inhibition
      shifted adaptor protein binding from the fusion oncoprotein to EGFR. Third, EGFR
      enabled bypass signaling to critical downstream pathways such as MAPK. While
      evidence of EGFR-mediated bypass signaling has been reported after ALK and ROS1
      blockade, our results extended this effect to RET and NTRK1 blockade and
      uncovered the other additional mechanisms in gene fusion-positive lung cancer
      cells, mouse models, and human clinical specimens before the onset of acquired
      drug resistance. Collectively, our findings show how EGFR signaling can provide a
      critical adaptive survival mechanism that allows cancer cells to evade oncogene
      specific inhibitors, providing a rationale to cotarget EGFR to reduce the risks
      of developing drug resistance. Cancer Res; 77(13); 3551-63. (c)2017 AACR.

PMID- 28428275
TI  - Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast
      Carcinomas.
AB  - The epithelial-to-mesenchymal transition (EMT) is a cell biological program that
      confers mesenchymal traits on carcinoma cells and drives their metastatic
      dissemination. It is unclear, however, whether the activation of EMT in carcinoma
      cells can change their susceptibility to immune attack. We demonstrate here that
      mammary tumor cells arising from more epithelial carcinoma cell lines expressed
      high levels of MHC-I, low levels of PD-L1, and contained within their stroma CD8+
      T cells and M1 (antitumor) macrophages. In contrast, tumors arising from more
      mesenchymal carcinoma cell lines exhibiting EMT markers expressed low levels of
      MHC-I, high levels of PD-L1, and contained within their stroma regulatory T
      cells, M2 (protumor) macrophages, and exhausted CD8+ T cells. Moreover, the more
      mesenchymal carcinoma cells within a tumor retained the ability to protect their
      more epithelial counterparts from immune attack. Finally, epithelial tumors were
      more susceptible to elimination by immunotherapy than corresponding mesenchymal
      tumors. Our results identify immune cells and immunomodulatory markers that can
      be potentially targeted to enhance the susceptibility of immunosuppressive tumors
      to various therapeutic regimens. Cancer Res; 77(15); 3982-9. (c)2017 AACR.

PMID- 28428276
TI  - Micellar Delivery of miR-34a Modulator Rubone and Paclitaxel in Resistant
      Prostate Cancer.
AB  - Treatment of prostate cancer with paclitaxel often fails due to the development
      of chemoresistance caused by downregulation of the tumor suppressor gene miR-34a.
      In this study, we demonstrate that codelivery of paclitaxel and 2'-hydroxy
      2,4,4',5,6'-pentamethoxychalcone (termed rubone) drives upregulation of miR-34a
      and chemosensitizes paclitaxel-resistant prostate cancer cells, killing both
      cancer stem-like cells (CSC) and bulk tumor cells. Rubone upregulated miR-34a and
      reversed its downstream target genes in DU145-TXR and PC3-TXR cells. Paclitaxel
      and rubone combination therapy inhibited tumor cell growth, migration, and CSC
      population growth. We synthesized poly(ethylene glycol)-block-poly(2-methyl-2
      carboxyl-propylene carbonate-graft-dodecanol; PEG-PCD) to prepare micelles. The
      drug-loading capacities were 9.70% +/- 0.10% and 5.34% +/- 0.02% for paclitaxel
      and rubone, respectively, controlling a drug release of 60.20% +/- 2.67% and
      60.62% +/- 4.35% release of paclitaxel and rubone at 24 hours. Delivery of miR
      34a and rubone decreased PC3-TXR cell viability with increasing paclitaxel
      concentration. Coincubation with a miR-34a inhibitor diminished the effect of
      rubone. Paclitaxel IC50 in PC3 and PC3-TXR cells was 55.6 and 2,580 nmol/L,
      respectively, but decreased to 49.8 and 93.2 nmol/L when treated in combination
      with rubone, demonstrating a reversal of paclitaxel resistance by rubone.
      Systemic administration of micelles carrying paclitaxel and rubone inhibited
      orthotopic prostate tumor growth in nude mice, compared with monotherapy, by
      reversing the expression of miR-34a, SIRT1, cyclin D1, and E-cadherin. In
      summary, our results showed how rubone acts as an efficient small-molecule
      modulator of miR-34a to reverse chemoresistance and further enhance the
      therapeutic efficacy of paclitaxel in paclitaxel-resistant prostate cancer.
      Cancer Res; 77(12); 3244-54. (c)2017 AACR.

PMID- 28428277
TI  - Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer.
AB  - The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic
      factor in breast cancer, but what drives immune infiltration remains unknown.
      Here we examine if clonal heterogeneity, total mutation load, neoantigen load,
      copy number variations (CNV), gene- or pathway-level somatic mutations, or
      germline polymorphisms (SNP) are associated with immune metagene expression in
      breast cancer subtypes. Thirteen published immune metagenes correlated separately
      with genomic metrics in the three major breast cancer subtypes. We analyzed RNA
      Seq, DNA copy number, mutation and germline SNP data of 627 ER+, 207 HER2+, and
      191 triple-negative (TNBC) cancers from The Cancer Genome Atlas. P-values were
      adjusted for multiple comparisons, and permutation testing was used to assess
      false discovery rates. Increased immune metagene expression associated
      significantly with lower clonal heterogeneity estimated by MATH score in all
      subtypes and with a trend for lower overall mutation, neoantigen, and CNV loads
      in TNBC and HER2+ cancers. In ER+ cancers, mutation load, neoantigen load, and
      CNV load weakly but positively associated with immune infiltration, which reached
      significance for overall mutation load only. No highly recurrent single gene or
      pathway level mutations associated with immune infiltration. High immune gene
      expression and lower clonal heterogeneity in TNBC and HER2+ cancers suggest an
      immune pruning effect and equilibrium between immune surveillance and clonal
      expansion. Thus, immune checkpoint inhibitors may tip the balance in favor of
      immune surveillance in these cancers. Cancer Res; 77(12); 3317-24. (c)2017 AACR.

PMID- 28428278
TI  - Oncogenic Role of SND1 in Development and Progression of Hepatocellular
      Carcinoma.
AB  - SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an
      oncogene in hepatocellular carcinoma (HCC). In this study, we show that
      hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC
      with partial penetrance and exhibit more highly aggressive HCC induced by
      chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase
      in inflammatory markers and spheroid-generating tumor-initiating cells (TIC).
      Mechanistic investigations defined roles for Akt and NF-kappaB signaling pathways
      in promoting TIC formation in Alb/SND1 mice. In human xenograft models of
      subcutaneous or orthotopic HCC, administration of the selective SND1 inhibitor
      3', 5'-deoxythymidine bisphosphate (pdTp), inhibited tumor formation without
      effects on body weight or liver function. Our work establishes an oncogenic role
      for SND1 in promoting TIC formation and highlights pdTp as a highly selective
      SND1 inhibitor as a candidate therapeutic lead to treat advanced HCC. Cancer Res;
      77(12); 3306-16. (c)2017 AACR.

PMID- 28428279
TI  - Interaction between Tumor Cell Surface Receptor RAGE and Proteinase 3 Mediates
      Prostate Cancer Metastasis to Bone.
AB  - Human prostate cancer often metastasizes to bone, but the biological basis for
      such site-specific tropism remains largely unresolved. Recent work led us to
      hypothesize that this tropism may reflect pathogenic interactions between RAGE, a
      cell surface receptor expressed on malignant cells in advanced prostate cancer,
      and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and
      hematopoietic cells within the bone marrow microenvironment. In this study, we
      establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to
      the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in
      vitro, inducing tumor cell motility through a nonproteolytic signal transduction
      cascade involving activation and phosphorylation of ERK1/2 and JNK1. In
      preclinical models of experimental metastasis, ectopic expression of RAGE on
      human prostate cancer cells was sufficient to promote bone marrow homing within a
      short timeframe. Our findings demonstrate how RAGE-PR3 interactions between human
      prostate cancer cells and the bone marrow microenvironment mediate bone
      metastasis during prostate cancer progression, with potential implications for
      prognosis and therapeutic intervention. Cancer Res; 77(12); 3144-50. (c)2017
      AACR.

PMID- 28428280
TI  - Role of CBX4 in the Colorectal Carcinoma Metastasis-Letter.

PMID- 28428281
TI  - Role of CBX4 in the Colorectal Carcinoma Metastasis-Response.

PMID- 28428282
TI  - Whither Radioimmunotherapy: To Be or Not To Be?
AB  - Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive
      results in preclinical experiments and in clinical trials conducted in
      radiosensitive malignancies, particularly B-cell lymphomas. Two "first
      generation," directly radiolabeled anti-CD20 antibodies, 131iodine-tositumomab
      and 90yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but
      have been little utilized because of a variety of medical, financial, and
      logistic obstacles. Newer technologies employing multistep "pretargeting"
      methods, particularly those utilizing bispecific antibodies, have greatly
      enhanced the therapeutic efficacy of radioimmunotherapy and diminished its
      toxicities. The dramatically improved therapeutic index of bispecific antibody
      pretargeting appears to be sufficiently compelling to justify human clinical
      trials and reinvigorate enthusiasm for radioimmunotherapy in the treatment of
      malignancies, particularly lymphomas. Cancer Res; 77(9); 2191-6. (c)2017 AACR.

PMID- 28428283
TI  - Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection.
AB  - Considerable advances in cancer-specific optical imaging have improved the
      precision of tumor resection. In comparison to traditional imaging modalities,
      this technology is unique in its ability to provide real-time feedback to the
      operating surgeon. Given the significant clinical implications of optical
      imaging, there is an urgent need to standardize surgical navigation tools and
      contrast agents to facilitate swift regulatory approval. Because fluorescence
      enhanced surgery requires a combination of both device and drug, each may be
      developed in conjunction, or separately, which are important considerations in
      the approval process. This report is the result of a one-day meeting held on May
      4, 2016 with officials from the National Cancer Institute, the FDA, members of
      the American Society of Image-Guided Surgery, and members of the World Molecular
      Imaging Society, which discussed consensus methods for FDA-directed human testing
      and approval of investigational optical imaging devices as well as contrast
      agents for surgical applications. The goal of this workshop was to discuss FDA
      approval requirements and the expectations for approval of these novel drugs and
      devices, packaged separately or in combination, within the context of optical
      surgical navigation. In addition, the workshop acted to provide clarity to the
      research community on data collection and trial design. Reported here are the
      specific discussion items and recommendations from this critical and timely
      meeting. Cancer Res; 77(9); 2197-206. (c)2017 AACR.

PMID- 28428284
TI  - Acute presentation of autoimmune hepatitis: a multicentre study with detailed
      histological evaluation in a large cohort of patients.
AB  - AIMS: Although liver biopsy is crucial to diagnose and guide treatment decisions,
      a detailed histological analysis of autoimmune hepatitis (AIH) with clinically
      acute presentations has not yet been performed. This study aimed to characterise
      the histological features and explore potential histological hallmarks to
      diagnose the acute presentation of AIH. METHODS: We systematically evaluated
      liver specimens of 87 adult patients with acute presentation of AIH
      retrospectively enrolled from Japanese multicentre facilities. Each histological
      feature was predefined by consensus based on the diagnostic criteria. RESULTS:
      Key findings were that acute presentation of AIH revealed histological features
      of both acute hepatitis and chronic hepatitis accompanying various degrees of
      fibrosis. The prominent features were lobular necrosis/inflammation (97.7%),
      plasma cell infiltration (96.4%), emperipolesis (89.3%), pigmented macrophages
      (84.5%), cobblestone appearance of hepatocytes (82.6%) and perivenular
      necroinflammatory activity, including centrilobular necrosis (81.4%).
      CONCLUSIONS: The acute presentation of AIH represents the entire histological
      spectrum of acute hepatitis and chronic hepatitis with various activity grades
      and fibrosis stages that clinically correspond to acute-onset AIH and acute
      exacerbation of classic AIH, respectively. Although there are no pathognomonic
      features for the pathological diagnosis, the prominent presence of lobular and
      perivenular necroinflammatory activity, pigmented macrophages and cobblestone
      appearance of hepatocytes in addition to the classic AIH features, such as plasma
      cell infiltration and emperipolesis, are useful for the pathological diagnosis of
      the acute presentation of AIH.

PMID- 28428285
TI  - Characterisation of GATA3 expression in invasive breast cancer: differences in
      histological subtypes and immunohistochemically defined molecular subtypes.
AB  - AIMS: GATA-binding protein 3 (GATA3) is a sensitive and relatively specific
      marker in breast and urothelial carcinomas. Its diagnostic utility in primary and
      metastatic breast cancers has been explored and confirmed. However, the
      relationship between GATA3 expression and different breast carcinoma intrinsic
      subtypes has not been specifically defined in the literature despite a few
      reports with a small number of cases. The aim of the current investigation is to
      clarify GATA3 expression among different histological subtypes and surrogate
      molecular breast carcinoma subtypes in a large series of cases. METHODS:
      Immunohistochemical staining of GATA3, GCDFP15 and mammaglobin was performed in a
      cohort of 1637 cases of primary invasive breast carcinoma. The association of
      GATA3 expression with different histological and surrogate intrinsic subtypes was
      assessed and compared with the expression of GCDFP15 and mammaglobin. RESULTS:
      The overall positivity of GATA3 across the various immunohistochemistry-based
      surrogate intrinsic subtypes was 99.51% for luminal A-like, 97.70% for luminal B
      like, 68.50% for HER2 overexpression and 20.16% for triple negative breast
      cancers. GATA3 expression was positively correlated with estrogen receptor (ER)
      positive (luminal subtypes) breast carcinomas. For luminal-like and HER2
      overexpression subtypes, GATA3 was much more sensitive than GCDFP15 and
      mammaglobin. For triple negative tumours, GATA3 was less sensitive than GCDFP15.
      CONCLUSIONS: GATA3 exhibits a relatively high sensitivity for breast carcinomas.
      It is more sensitive than GCDFP15 and mammaglobin in luminal-like and HER2
      overexpression subtypes. GATA3 expression is associated with breast carcinomas of
      luminal subtype and low histological grade.

PMID- 28428286
TI  - A Genetic Analysis of the Caenorhabditis elegans Detoxification Response.
AB  - Oxidative damage contributes to human diseases of aging including diabetes,
      cancer, and cardiovascular disorders. Reactive oxygen species resulting from
      xenobiotic and endogenous metabolites are sensed by a poorly understood process,
      triggering a cascade of regulatory factors and leading to the activation of the
      transcription factor Nrf2 (Nuclear factor-erythroid-related factor 2, SKN-1 in
      Caenorhabditis elegans). Nrf2/SKN-1 activation promotes the induction of the
      phase II detoxification system that serves to limit oxidative stress. We have
      extended a previous C. elegans genetic approach to explore the mechanisms by
      which a phase II enzyme is induced by endogenous and exogenous oxidants. The xrep
      (xenobiotics response pathway) mutants were isolated as defective in their
      ability to properly regulate the induction of a glutathione S-transferase (GST)
      reporter. The xrep-1 gene was previously identified as wdr-23, which encodes a C.
      elegans homolog of the mammalian beta-propeller repeat-containing protein WDR-23
      Here, we identify and confirm the mutations in xrep-2, xrep-3, and xrep-4 The
      xrep-2 gene is alh-6, an ortholog of a human gene mutated in familial
      hyperprolinemia. The xrep-3 mutation is a gain-of-function allele of skn-1 The
      xrep-4 gene is F46F11.6, which encodes a F-box-containing protein. We demonstrate
      that xrep-4 alters the stability of WDR-23 (xrep-1), a key regulator of SKN-1
      (xrep-3). Epistatic relationships among the xrep mutants and their interacting
      partners allow us to propose an ordered genetic pathway by which endogenous and
      exogenous stressors induce the phase II detoxification response.

PMID- 28428288
TI  - Complete Genome Sequence of the Streptococcus gallolyticus subsp. gallolyticus
      Strain DSM 16831.
AB  - Streptococcus gallolyticus subsp. gallolyticus DSM 16831 is an intriguing strain
      because of its low virulent phenotype compared to other isolates. We present here
      the complete genome sequence for this strain isolated from koala feces.

PMID- 28428287
TI  - Smurf Downregulates Echinoid in the Amnioserosa To Regulate Drosophila Dorsal
      Closure.
AB  - Drosophila dorsal closure is a morphogenetic movement that involves flanking
      epidermal cells, assembling actomyosin cables, and migrating dorsally over the
      underlying amnioserosa to seal at the dorsal midline. Echinoid (Ed)-a cell
      adhesion molecule of adherens junctions (AJs)-participates in several
      developmental processes. The disappearance of Ed from the amnioserosa is required
      to define the epidermal leading edge for actomyosin cable assembly and
      coordinated cell migration. However, the mechanism by which Ed is cleared from
      amnioserosa is unknown. Here, we show that Ed is cleared in amnioserosa by both
      transcriptional and post-translational mechanisms. First, Ed mRNA transcription
      was repressed in amnioserosa prior to the onset of dorsal closure. Second, the
      ubiquitin ligase Smurf downregulated pretranslated Ed by binding to the PPXY
      motif of Ed. During dorsal closure, Smurf colocalized with Ed at AJs, and Smurf
      overexpression prematurely degraded Ed in the amnioserosa. Conversely, Ed
      persisted in the amnioserosa of Smurf mutant embryos, which, in turn, affected
      actomyosin cable formation. Together, our results demonstrate that
      transcriptional repression of Ed followed by Smurf-mediated downregulation of
      pretranslated Ed in amnioserosa regulates the establishment of a taut leading
      edge during dorsal closure.

PMID- 28428289
TI  - Draft Genome Sequence of Methylocaldum sp. Strain 14B, an Obligate Hydrogen
      Sulfide-Tolerant Methanotrophic Strain That Can Convert Biogas to Methanol.
AB  - The draft genome sequence of Methylocaldum sp. 14B, an obligate methanotrophic
      strain isolated from solid-state anaerobic digestion systems, is reported here.
      Strain 14B possesses genes for methane oxidation and exhibited tolerance to H2S.

PMID- 28428290
TI  - Draft Genome Sequence of Acinetobacter johnsonii C6, an Environmental Isolate
      Engaging in Interspecific Metabolic Interactions.
AB  - Acinetobacter johnsonii C6 originates from creosote-polluted groundwater and
      performs ecological and evolutionary interactions with Pseudomonas putida in
      biofilms. The draft genome of A. johnsonii C6 is 3.7 Mbp and was shaped by mobile
      genetic elements. It reveals genes facilitating the biodegradation of aromatic
      hydrocarbons and resistance to antimicrobials and metals.

PMID- 28428291
TI  - Complete Genome Sequence of a Novel Satellite Virus Associated with Cassava
      Plants.
AB  - A novel satellite virus of 1,228 bp in length was found in a single cassava
      plant. Bioinformatic analyses show that it has two open reading frames (ORFs) in
      its genome, probably encoding a coat protein of 156 and a putative protein of 90
      amino acids.

PMID- 28428292
TI  - Shigella Draft Genome Sequences: Resources for Food Safety and Public Health.
AB  - Shigella is a major foodborne pathogen that infects humans and nonhuman primates
      and is the major cause of dysentery and reactive arthritis worldwide. This is the
      initial public release of 16 Shigella genome sequences from four species
      sequenced as part of the 100K Pathogen Genome Project.

PMID- 28428293
TI  - Draft Genome Sequence of Bacillus cereus LA2007, a Human-Pathogenic Isolate
      Harboring Anthrax-Like Plasmids.
AB  - We present the genome sequence of Bacillus cereus LA2007, a strain isolated in
      2007 from a fatal pneumonia case in Louisiana. Sequence-based genome analysis
      revealed that LA2007 carries a plasmid highly similar to Bacillus anthracis pXO1,
      including the genes responsible for the production and regulation of anthrax
      toxin.

PMID- 28428294
TI  - Complete and Assembled Genome Sequence of Lactobacillus plantarum RI-113 Isolated
      from Salami.
AB  - We present here the complete genome sequence of Lactobacillus plantarum RI-113, a
      strain isolated from salami, which was determined using single-molecule real-time
      sequencing.

PMID- 28428295
TI  - Multiple Genome Sequences of Heteropolysaccharide-Forming Acetic Acid Bacteria.
AB  - We report here the complete genome sequences of the acetic acid bacteria (AAB)
      Acetobacter aceti TMW 2.1153, A. persici TMW 2.1084, and Neoasaia chiangmaiensis
      NBRC 101099, which secrete biotechnologically relevant heteropolysaccharides
      (HePSs) into their environments. Upon genome sequencing of these AAB strains, the
      corresponding HePS biosynthesis pathways were identified.

PMID- 28428296
TI  - Complete Genome Sequences of Mycobacterium kansasii Strains Isolated from Rhesus
      Macaques.
AB  - Mycobacterium kansasii is a nontuberculous mycobacterium. It causes opportunistic
      infections with pulmonary and extrapulmonary manifestations. We report here the
      complete genome sequences of two M. kansasii strains isolated from rhesus
      macaques. We performed genome comparisons with human and environmental isolates
      of M. kansasii to assess the genomic diversity of this species.

PMID- 28428297
TI  - Complete Genome Sequence of Mycobacterium avium subsp. hominissuis Strain H87
      Isolated from an Indoor Water Sample.
AB  - Mycobacterium avium subsp. hominissuis is an environmentally acquired bacterium
      known to cause pulmonary and soft tissue infections, lymphadenitis, and
      disseminated disease in humans. We report here the complete genome sequence of
      strain H87, isolated from an indoor water sample, as a single circular chromosome
      of 5,626,623 bp with a G+C content of 68.8%.

PMID- 28428298
TI  - Genome Sequence of Staphylococcus saprophyticus DPC5671, a Strain Isolated from
      Cheddar Cheese.
AB  - The draft genome sequence of Staphylococcus saprophyticus DPC5671, isolated from
      cheddar cheese, was determined. S. saprophyticus is a common Gram-positive
      bacterium detected on the surface of smear-ripened cheese and other fermented
      foods.

PMID- 28428299
TI  - Draft Genome Sequence of Tritrichomonas foetus Strain K.
AB  - The protist Tritrichomonas foetus (Excavata, Parabasalia) is a parasite that
      causes bovine and feline trichomonosis. Bovine trichomonosis is a venereal
      disease that leads to abortion and reproductive problems in herds. Feline
      trichomonosis affects domestic cats. Here, we report the genome sequence of the
      T. foetus K strain, isolated in Brazil.

PMID- 28428300
TI  - Draft Genome Sequence of Enterococcus casseliflavus PAVET15 Obtained from the
      Oviduct Infection of the Cattle Tick (Rhipicephalus microplus) in Jiutepec,
      Morelos, Mexico.
AB  - Enterococcus spp. are Gram-positive lactic acid-producing bacteria found in the
      intestinal tracts of animals, like mammals, birds, and arthropods. Enterococcus
      spp. may cause oportunistic infections in vertebrate and invertebrate hosts. We
      report here the draft genome sequence of Enterococcus casseliflavus PAVET15
      containing 3,722,480 bp, with 80 contigs, an N50 of 179,476 bp, and 41.93% G+C
      content.

PMID- 28428301
TI  - Whole-Genome Sequence of Corynebacterium pseudotuberculosis PA04, Isolated from
      the Lymph Node of a Sheep in the Amazon, Brazil.
AB  - This study reports the complete genome sequence of Corynebacterium
      pseudotuberculosis strain PA04, isolated from a sheep in the Amazon, Brazil. This
      bacterium is the etiological agent of caseous lymphadenitis. This genome contains
      2,338,093 bp, 52.2% G+C content, and a total of 2,104 coding sequences (CDSs), 41
      pseudogenes, 12 rRNAs, and 49 tRNAs.

PMID- 28428302
TI  - Draft Genome Sequence of a Multidrug-Resistant Pseudomonas aeruginosa Strain
      Isolated from a Patient with a Urinary Tract Infection in Khartoum, Sudan.
AB  - Pseudomonas aeruginosa infection is difficult to treat due to the presence of
      antibiotic resistance determinants. Here, we report the genome sequence of a
      multidrug-resistant P. aeruginosa strain isolated from a patient with a urinary
      tract infection in 2015.

PMID- 28428303
TI  - Genome Sequence of Microbacterium sp. Strain TPU 3598, a Lumichrome Producer.
AB  - We report here the genome sequence of Microbacterium sp. strain TPU 3598,
      previously described as a producer of lumichrome. The sequenced genome size is
      3,787,270 bp, the average G+C content is 68.39%, and 3,674 protein-coding
      sequences are predicted.

PMID- 28428304
TI  - Complete Genome Sequence of Spiroplasma citri Strain R8-A2T, Causal Agent of
      Stubborn Disease in Citrus Species.
AB  - Spiroplasma citri causes stubborn disease in Citrus spp. and diseases in other
      plants. Here, we report the nucleotide sequence of the 1,599,709-bp circular
      chromosome and two plasmids of S. citri strain R8-A2T This information will
      facilitate analyses to understand spiroplasmal pathogenicity and evolutionary
      adaptations to lifestyles in plants and arthropod hosts.

PMID- 28428305
TI  - Draft Genome Sequence of the Plasmid-Free Lactococcus lactis subsp. lactis Strain
      LMG 19460.
AB  - We report here the draft genome sequence of the plasmid-free Lactococcus lactis
      subsp. lactis strain LMG 19460. This strain has potential application for a cost
      effective production of food-grade plasmid DNA to use in DNA vaccines, produce
      recombinant proteins, and be used as a mucosal delivery vehicle of therapeutic
      molecules.

PMID- 28428306
TI  - Draft Nuclear Genome Sequence of the Liquid Hydrocarbon-Accumulating Green
      Microalga Botryococcus braunii Race B (Showa).
AB  - Botryococcus braunii has long been known as a prodigious producer of liquid
      hydrocarbon oils that can be converted into combustion engine fuels. This draft
      genome for the B race of B. braunii will allow researchers to unravel important
      hydrocarbon biosynthetic pathways and identify possible regulatory networks
      controlling this unusual metabolism.

PMID- 28428307
TI  - Draft Genome Sequences of Three Listeria monocytogenes Isolates from Foods in
      China.
AB  - Listeria monocytogenes is a foodborne pathogen of global concern because of the
      high mortality rate among patients. The draft genome sequences of three L.
      monocytogenes strains isolated from foods are reported here. The availability of
      these genomes should provide useful information on the genomic diversity of L.
      monocytogenes isolated from foods in China.

PMID- 28428308
TI  - Genome Sequence of Canine Adenovirus Type 1 Isolated from a Wolf (Canis lupus) in
      Southern Italy.
AB  - Canine adenovirus type 1 (CAdV-1), a DNA virus of the family Adenoviridae, causes
      infectious canine hepatitis, a highly contagious disease primarily affecting
      canids. In this report, we describe the isolation and whole-genome sequence of a
      CAdV-1 isolate from the liver of a free-ranging wolf (Canis lupus).

PMID- 28428309
TI  - Draft Genome Sequences of Two Highly Erythromycin-Resistant Streptococcus
      gallolyticus subsp. gallolyticus Isolates Containing a Novel Tn916-Like Element,
      Tn6331.
AB  - Recently, we reported the draft genome sequence of Streptococcus gallolyticus
      NTS31106099. It was found to contain a previously unknown putative Tn916-like
      conjugative transposon, Tn6263 Here, we report the draft genome sequences of two
      other clinical isolates, NTS31301958 and NTS31307655. Both of them contain
      another novel element, Tn6331, which is highly similar to Tn6263.

PMID- 28428310
TI  - Complete Genome Sequence of Pseudomonas protegens H78, a Plant Growth-Promoting
      Rhizobacterium.
AB  - The plant growth-promoting rhizobacterium Pseudomonas protegens H78, which was
      isolated from the rhizosphere of oilseed rape in Shanghai, can produce a large
      array of antibiotics with a broad spectrum of activities. Here, we report the
      annotated complete genome sequence of P. protegens H78.

PMID- 28428311
TI  - Complete Genome Characterization of Chinese Porcine Deltacoronavirus Strain
      CHN/Tianjin/2016.
AB  - As we all know, porcine deltacoronavirus was first detected in Hong Kong, China.
      Here, we report the complete genome sequence of the Chinese porcine
      deltacoronavirus strain CHN/Tianjin/2016, which was collected and amplified from
      clinical fecal samples in March of 2016.

PMID- 28428312
TI  - Draft Genome Sequence of a Chromium-Reducing Strain, Pseudomonas fluorescens
      S613, Isolated from a Chromium-Contaminated Aquifer in Los Alamos, New Mexico.
AB  - In this report, a chromium-reducing bacterium, Pseudomonas fluorescens strain
      S613, was isolated from a Cr(VI)-contaminated aquifer at Los Alamos, NM, and
      sequenced. The size of the draft genome sequence is approximately 6.7 Mb.

PMID- 28428313
TI  - Draft Genome Sequences of Two Hydrogenogenic Carboxydotrophic Bacteria,
      Carboxydocella sp. Strains JDF658 and ULO1, Isolated from Two Distinct Volcanic
      Fronts in Japan.
AB  - Hydrogenogenic carboxydotrophs may provide hydrogen as primary energy for the
      microbial community via carbon monoxide oxidation. To investigate the genetics of
      carbon monoxide metabolism, we report here the draft genome sequences of the
      hydrogenogenic carboxydotrophs Carboxydocella sp. strains JDF658 (2.60 Mbp; G+C
      content, 49.2%) and ULO1 (2.70 Mbp; G+C content, 48.8%).

PMID- 28428314
TI  - Complete Genome Sequence of the Original Escherichia coli Isolate, Strain NCTC86.
AB  - Escherichia coli is the most well-studied bacterium and a common colonizer of the
      lower mammalian gastrointestinal tract. We report here the complete genome
      sequence of the original Escherichia coli isolate, strain NCTC86, which was
      described by Theodor Escherich, for whom the genus is named.

PMID- 28428315
TI  - Improved High-Quality Draft Genome Sequence and Annotation of Burkholderia
      contaminans LMG 23361T.
AB  - Burkholderia contaminans LMG 23361 is the type strain of the species isolated
      from the milk of a dairy sheep with mastitis. Some pharmaceutical products
      contain disinfectants such as benzalkonium chloride (BZK) and previously we
      reported that B. contaminans LMG 23361T possesses the ability to inactivate BZK
      with high biodegradation rates. Here, we report an improved high-quality draft
      genome sequence of this strain.

PMID- 28428316
TI  - Genome Sequences of Cluster K Mycobacteriophages DrHayes, Urkel, and
      SamuelLPlaqson.
AB  - Mycobacteriophages DrHayes, Urkel, and SamuelLPlaqson were isolated from soil
      samples in Spokane, WA, using Mycobacterium smegmatis mc2155 grown at room
      temperature. The three genomes differ by only a few nucleotides, are 60,526 bp
      long, have 97 predicted protein-coding genes and one tRNA gene, and are members
      of subcluster K1.

PMID- 28428317
TI  - Complete Nucleotide Sequence of an Isolate of Grapevine Satellite Virus and
      Evidence for the Presence of Multimeric Forms in an Infected Grapevine.
AB  - The complete nucleotide sequence of an isolate of grapevine satellite virus (GV
      Sat) was determined by next-generation sequencing (NGS) and compared with the
      single available complete sequence. The NGS data unexpectedly provided evidence
      for the existence of multimeric forms of GV-Sat, which were experimentally
      confirmed, allowing the redefinition of GV-Sat genomic ends.

PMID- 28428319
TI  - In This Issue of Diabetes Care.

PMID- 28428318
TI  - Bottom-up construction of a superstructure in a porous uranium-organic crystal.
AB  - Bottom-up construction of highly intricate structures from simple building blocks
      remains one of the most difficult challenges in chemistry. We report a
      structurally complex, mesoporous uranium-based metal-organic framework (MOF) made
      from simple starting components. The structure comprises 10 uranium nodes and
      seven tricarboxylate ligands (both crystallographically nonequivalent), resulting
      in a 173.3-angstrom cubic unit cell enclosing 816 uranium nodes and 816 organic
      linkers-the largest unit cell found to date for any nonbiological material. The
      cuboctahedra organize into pentagonal and hexagonal prismatic secondary
      structures, which then form tetrahedral and diamond quaternary topologies with
      unprecedented complexity. This packing results in the formation of colossal
      icosidodecahedral and rectified hexakaidecahedral cavities with internal
      diameters of 5.0 nanometers and 6.2 nanometers, respectively-ultimately giving
      rise to the lowest-density MOF reported to date.

PMID- 28428320
TI  - Modern Sulfonylureas: Dangerous or Wrongly Accused?

PMID- 28428321
TI  - Sulfonylureas and the Risks of Cardiovascular Events and Death: A Methodological
      Meta-Regression Analysis of the Observational Studies.
AB  - Recent randomized trials have compared the newer antidiabetic agents to
      treatments involving sulfonylureas, drugs associated with increased
      cardiovascular risks and mortality in some observational studies with conflicting
      results. We reviewed the methodology of these observational studies by searching
      MEDLINE from inception to December 2015 for all studies of the association
      between sulfonylureas and cardiovascular events or mortality. Each study was
      appraised with respect to the comparator, the outcome, and study design-related
      sources of bias. A meta-regression analysis was used to evaluate heterogeneity. A
      total of 19 studies were identified, of which six had no major design-related
      biases. Sulfonylureas were associated with an increased risk of cardiovascular
      events and mortality in five of these studies (relative risks 1.16-1.55).
      Overall, the 19 studies resulted in 36 relative risks as some studies assessed
      multiple outcomes or comparators. Of the 36 analyses, metformin was the
      comparator in 27 (75%) and death was the outcome in 24 (67%). The relative risk
      was higher by 13% when the comparator was metformin, by 20% when death was the
      outcome, and by 7% when the studies had design-related biases. The lowest
      predicted relative risk was for studies with no major bias, comparator other than
      metformin, and cardiovascular outcome (1.06 [95% CI 0.92-1.23]), whereas the
      highest was for studies with bias, metformin comparator, and mortality outcome
      (1.53 [95% CI 1.43-1.65]). In summary, sulfonylureas were associated with an
      increased risk of cardiovascular events and mortality in the majority of studies
      with no major design-related biases. Among studies with important biases, the
      association varied significantly with respect to the comparator, the outcome, and
      the type of bias. With the introduction of new antidiabetic drugs, the use of
      appropriate design and analytical tools will provide their more accurate
      cardiovascular safety assessment in the real-world setting.

PMID- 28428322
TI  - Glycemic Control During Continuous Subcutaneous Insulin Infusion Versus Multiple
      Daily Insulin Injections in Type 2 Diabetes: Individual Patient Data Meta
      analysis and Meta-regression of Randomized Controlled Trials.
AB  - OBJECTIVE: To compare glycemic control during continuous subcutaneous insulin
      infusion (CSII) and multiple daily insulin injections (MDI) in people with type 2
      diabetes to identify patient characteristics that determine those best treated by
      CSII. RESEARCH DESIGN AND METHODS: Randomized controlled trials were selected
      comparing HbA1c during CSII versus MDI in people with type 2 diabetes. Data
      sources included Cochrane database and Ovid Medline. We explored patient-level
      determinants of final HbA1c level and insulin dose using Bayesian meta-regression
      models of individual patient data and summary effects using two-step meta
      analysis. Hypoglycemia data were unavailable. RESULTS: Five trials were
      identified, with 287 patients randomized to receive MDI and 303 to receive CSII.
      Baseline HbA1c was the best determinant of final HbA1c: HbA1c difference (%) =
      1.575 - (0.216 [95% credible interval 0.371-0.043] * baseline HbA1c) for all
      trials, but with largest effect in the trial with prerandomization optimization
      of control. Baseline insulin dose was best predictor of final insulin dose:
      insulin dose difference (units/kg) = 0.1245 - (0.382 [0.510-0.254] * baseline
      insulin dose). Overall HbA1c difference was -0.40% (-0.86 to 0.05 [-4.4 mmol/mol
      (-9.4 to 0.6)]). Overall insulin dose was reduced by -0.25 units/kg (-0.31 to 
      0.19) (26% reduction on CSII), and by -24.0 units/day (-30.6 to -17.5). Mean
      weight did not differ between treatments (0.08 kg [-0.33 to 0.48]). CONCLUSIONS:
      CSII achieves better glycemic control than MDI in people with poorly controlled
      type 2 diabetes, with ~26% reduction in insulin requirements and no weight
      change. The best effect is in those worst controlled and with the highest insulin
      dose at baseline.

PMID- 28428323
TI  - Insulitis in Autoantibody-Positive Pancreatic Donor With History of Gestational
      Diabetes Mellitus.

PMID- 28428325
TI  - Comment on Chen et al. Risk of Developing Type 2 Diabetes in Adolescents and
      Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study.
      Diabetes Care 2016;39:788-793.

PMID- 28428326
TI  - Response to Comment on Chen et al. Risk of Developing Type 2 Diabetes in
      Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide
      Longitudinal Study. Diabetes Care 2016;39:788-793.

PMID- 28428327
TI  - Comment on O'Brien et al. Hormonal Contraception and Risk of Thromboembolism in
      Women With Diabetes. Diabetes Care 2017;40:233-238.

PMID- 28428328
TI  - Response to Comment on O'Brien et al. Hormonal Contraception and Risk of
      Thromboembolism in Women With Diabetes. Diabetes Care 2017;40:233-238.

PMID- 28428329
TI  - Visualization of RNA structure models within the Integrative Genomics Viewer.
AB  - Analyses of the interrelationships between RNA structure and function are
      increasingly important components of genomic studies. The SHAPE-MaP strategy
      enables accurate RNA structure probing and realistic structure modeling of
      kilobase-length noncoding RNAs and mRNAs. Existing tools for visualizing RNA
      structure models are not suitable for efficient analysis of long, structurally
      heterogeneous RNAs. In addition, structure models are often advantageously
      interpreted in the context of other experimental data and gene annotation
      information, for which few tools currently exist. We have developed a module
      within the widely used and well supported open-source Integrative Genomics Viewer
      (IGV) that allows visualization of SHAPE and other chemical probing data,
      including raw reactivities, data-driven structural entropies, and data
      constrained base-pair secondary structure models, in context with linear genomic
      data tracks. We illustrate the usefulness of visualizing RNA structure in the IGV
      by exploring structure models for a large viral RNA genome, comparing bacterial
      mRNA structure in cells with its structure under cell- and protein-free
      conditions, and comparing a noncoding RNA structure modeled using SHAPE data with
      a base-pairing model inferred through sequence covariation analysis.

PMID- 28428330
TI  - Genomic responses to the socio-sexual environment in male Drosophila melanogaster
      exposed to conspecific rivals.
AB  - Socio-sexual environments have profound effects on fitness. Local sex ratios can
      alter the threat of sexual competition, to which males respond via plasticity in
      reproductive behaviors and ejaculate composition. In Drosophila melanogaster,
      males detect the presence of conspecific, same-sex mating rivals prior to mating
      using multiple, redundant sensory cues. Males that respond to rivals gain
      significant fitness benefits by altering mating duration and ejaculate
      composition. Here we investigated the underlying genome-wide changes involved. We
      used RNA-seq to analyze male transcriptomic responses 2, 26, and 50 h after
      exposure to rivals, a time period that was previously identified as encompassing
      the major facets of male responses to rivals. The results showed a strong early
      activation of multiple sensory genes in the head-thorax (HT), prior to the
      expression of any phenotypic differences. This gene expression response was
      reduced by 26 h, at the time of maximum phenotypic change, and shut off by 50 h.
      In the abdomen (A), fewer genes changed in expression and gene expression
      responses appeared to increase over time. The results also suggested that
      different sets of functionally equivalent genes might be activated in different
      replicates. This could represent a mechanism by which robustness is conferred
      upon highly plastic traits. Overall, our study reveals that mRNA-seq can identify
      subtle genomic signatures characteristic of flexible behavioral phenotypes.

PMID- 28428331
TI  - A Personalized Model of COQ2 Nephropathy Rescued by the Wild-Type COQ2 Allele or
      Dietary Coenzyme Q10 Supplementation.
AB  - Clinical studies have identified patients with nephrotic syndrome caused by
      mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid
      component of the mitochondrial electron transport chain and an important
      antioxidant. However, the cellular mechanisms through which these mutations
      induce podocyte injury remain obscure. Here, we exploited the striking
      similarities between Drosophila nephrocytes and human podocytes to develop a
      Drosophila model of these renal diseases, and performed a systematic in vivo
      analysis assessing the role of CoQ10 pathway genes in renal function. Nephrocyte
      specific silencing of Coq2, Coq6, and Coq8, which are genes involved in the CoQ10
      pathway that have been associated with genetic nephrotic syndrome in humans,
      induced dramatic adverse changes in these cells. In particular, silencing of Coq2
      led to an abnormal localization of slit diaphragms, collapse of lacunar channels,
      and more dysmorphic mitochondria. In addition, Coq2-deficient nephrocytes showed
      elevated levels of autophagy and mitophagy, increased levels of reactive oxygen
      species, and increased sensitivity to oxidative stress. Dietary supplementation
      with CoQ10 at least partially rescued these defects. Furthermore, expressing the
      wild-type human COQ2 gene specifically in nephrocytes rescued the defective
      protein uptake, but expressing the mutant allele derived from a patient with COQ2
      nephropathy did not. We conclude that transgenic Drosophila lines carrying
      mutations in the CoQ10 pathway genes are clinically relevant models with which to
      explore the pathogenesis of podocyte injury and could serve as a new platform to
      test novel therapeutic approaches.

PMID- 28428334
TI  - Four Groups Win CRUK "Grand Challenge".
AB  - Four research teams were each awarded Cancer Research UK's "Grand Challenge"
      prize of up to L20 million, or about $25 million, over 5 years. The winning teams
      bring together scientists and technologists from around the world to tackle some
      of the most pressing unsolved problems in cancer research.

PMID- 28428332
TI  - Education in Nephrology Fellowship: A Survey-Based Needs Assessment.
AB  - Educational needs assessments for nephrology fellowship training are limited.
      This study assessed fellows' perceptions of current educational needs and
      interest in novel modalities that may improve their educational experience and
      quantified educational resources used by programs and fellows. We distributed a
      seven-question electronic survey to all United States-based fellows receiving
      complimentary American Society of Nephrology (ASN) membership at the end of the
      2015-2016 academic year in conjunction with the ASN Nephrology Fellows Survey.
      One third (320 of 863; 37%) of fellows in Accreditation Council for Graduate
      Medical Education-accredited positions responded. Most respondents rated overall
      quality of teaching in fellowship as either "good" (37%) or "excellent" (44%),
      and most (55%) second-year fellows felt "fully prepared" for independent
      practice. Common educational resources used by fellows included UpToDate, Journal
      of the American Society of Nephrology/Clinical Journal of the American Society of
      Nephrology, and Nephrology Self-Assessment Program; others-including ASN's online
      curricula-were used less often. Fellows indicated interest in additional
      instruction in several core topics, including home dialysis modalities,
      ultrasonography, and pathology. Respondents strongly supported interventions to
      improve pathology instruction and increase time for physiology and clinical
      review. In conclusion, current nephrology fellows perceive several gaps in
      training. Innovation in education and training is needed to better prepare future
      nephrologists for the growing challenges of kidney care.

PMID- 28428335
TI  - Corrigendum.

PMID- 28428333
TI  - The MicroRNA-199a/214 Cluster Targets E-Cadherin and Claudin-2 and Promotes High
      Glucose-Induced Peritoneal Fibrosis.
AB  - Serum response factor (SRF) was found to be involved in the phenotypic transition
      and fibrosis of the peritoneal membrane during treatment with peritoneal dialysis
      (PD), but the exact mechanism remains unclear. SRF regulates microRNAs (miRNAs)
      that contain the SRF-binding consensus (CArG) element in the promoter region.
      Therefore, we investigated whether the miR-199a/214 gene cluster, which contains
      a CArG element in its promoter, is directly regulated by SRF. High-glucose (HG)
      treatment significantly unregulated the expression of the miR-199a-5p/214-3p gene
      cluster in human peritoneal mesothelial cells (HPMCs). By chromatin
      immunoprecipitation and reporter assays, we found that SRF binds to the miR-199a
      5p/214-3p gene cluster promoter after HG stimulation. In vitro, in HPMCs,
      silencing of miR-199a-5p or miR-214-3p inhibited the HG-induced phenotypic
      transition and cell migration but enhanced cell adhesion, whereas ectopic
      expression of mimic oligonucleotides had the opposite effects. Both miR-199a-5p
      and miR-214-3p targeted claudin-2 and E-cadherin mRNAs. In a PD rat model,
      treatment with an SRF inhibitor silenced miR-199a-5p and miR-214-3p and
      alleviated HG-PD fluid-induced damage and fibrosis. Overall, this study reveals a
      novel SRF-miR-199a/miR-214-E-cadherin/claudin-2 axis that mediates damage and
      fibrosis in PD.

PMID- 28428336
TI  - Corrigendum.

PMID- 28428337
TI  - Factual text and emotional pictures: overcoming a false dichotomy of cigarette
      warning labels.
AB  - BACKGROUND: In reviewing the first set of pictorial warning labels in the USA,
      the courts equated textual labels with facts and information, and images with
      emotion. This study tested the differences in perceived informativeness and
      emotion between textual and pictorial cigarette warning labels. METHODS: An
      online study with 1838 US adults who were non-smokers (n=764), transitioning
      smokers (quit smoking in the past 2 years or currently trying to quit, n=505) or
      current smokers (n=569). Each participant evaluated 9 out of 81 text and
      pictorial cigarette warning labels. Participants reported to what extent they
      perceived the label as informative and factual and the negative emotions they
      felt while looking at each label. We used linear mixed models to account for the
      nesting of multiple observations within each participant. RESULTS: There were no
      significant differences in perceived informativeness between textual (mean 6.15
      on a 9-point scale) and pictorial labels (6.14, p=0.80, Cohen's d=0.003). Textual
      labels evoked slightly less emotion (4.21 on a 9-point scale) than pictorial
      labels (4.42, p<0.001, Cohen's d=0.08). Perceived informativeness and emotion
      were strongly correlated (Pearson r=0.53, p<0.001). CONCLUSION: Our findings
      contradict courts' conclusions that pictorial messages are emotional and not
      factual. Pictorial labels are rated as informative and factual, textual labels
      evoke emotion, and emotionality and informativeness are strongly correlated.
      These findings serve as evidence for the Food and Drug Administration (FDA) to
      counteract the claim that pictorial warning labels, by definition, are not
      'purely factual and uncontroversial'.

PMID- 28428338
TI  - Strategies to prevent death by suicide: meta-analysis of randomised controlled
      trials.
AB  - BackgroundFew randomised controlled trials (RCTs) have shown decreases in
      suicide.AimsTo identify interventions for preventing suicide.MethodWe searched
      EMBASE and Medline from inception until 31 December 2015. We included RCTs
      comparing prevention strategies with control. We pooled odds ratios (ORs) for
      suicide using the Peto method.ResultsAmong 8647 citations, 72 RCTs and 6 pooled
      analyses met inclusion criteria. Three RCTs (n = 2028) found that the World
      Health Organization (WHO) brief intervention and contact (BIC) was associated
      with significantly lower odds of suicide (OR = 0.20, 95% CI 0.09-0.42). Six RCTs
      (n = 1040) of cognitive-behavioural therapy (CBT) for suicide prevention and six
      RCTs of lithium (n = 619) yielded non-significant findings (OR = 0.34, 95% CI
      0.12-1.03 and OR = 0.23, 95% CI 0.05-1.02, respectively).ConclusionsThe WHO BIC
      is a promising suicide prevention strategy. No other intervention showed a
      statistically significant effect in reducing suicide.

PMID- 28428339
TI  - Association between body size, weight change and depression: systematic review
      and meta-analysis.
AB  - BackgroundThe association between body size, weight change and depression has not
      been systematically summarised, especially for individuals who are
      underweight.AimsTo conduct a systematic review and a meta-analysis to examine the
      association between indices of body size, weight change and depression.MethodA
      total of 183 studies were selected. Fully adjusted hazard ratios (HRs) or odds
      ratios (ORs) were extracted. A total of 76 studies contributed to data synthesis
      with a random-effect model, and subgroup analyses were conducted to evaluate the
      effect of potential moderators.ResultsIn cohort studies, underweight at baseline
      increased the risk of subsequent depression (OR = 1.16, 95% CI 1.08-1.24).
      Overweight (BMI 25-29.9 kg/m2) showed no statistically significant relationship
      with depression overall; however, the subgroup analyses found different results
      according to gender (men: OR = 0.84, 95% CI 0.72-0.97, women: OR = 1.16, 95% CI
      1.07-1.25). In cross-sectional designs, obesity with BMI >40 kg/m2 showed a
      greater pooled odds ratio than obesity with BMI >30 kg/m2ConclusionsBoth
      underweight and obesity increase the risk of depression. The association between
      overweight and depression differs by gender.

PMID- 28428340
TI  - Modeling language shift.

PMID- 28428341
TI  - Ctf4-related protein recruits LHP1-PRC2 to maintain H3K27me3 levels in dividing
      cells in Arabidopsis thaliana.
AB  - Polycomb Repressive Complex (PRC) 2 catalyzes the H3K27me3 modification that
      warrants inheritance of a repressive chromatin structure during cell division,
      thereby assuring stable target gene repression in differentiated cells. It is
      still under investigation how H3K27me3 is passed on from maternal to filial
      strands during DNA replication; however, cell division can reinforce H3K27me3
      coverage at target regions. To identify novel factors involved in the Polycomb
      pathway in plants, we performed a forward genetic screen for enhancers of the
      like heterochromatin protein 1 (lhp1) mutant, which shows relatively mild
      phenotypic alterations compared with other plant PRC mutants. We mapped enhancer
      of lhp1 (eol) 1 to a gene related to yeast Chromosome transmission fidelity 4
      (Ctf4) based on phylogenetic analysis, structural similarities, physical
      interaction with the CMG helicase component SLD5, and an expression pattern
      confined to actively dividing cells. A combination of eol1 with the curly leaf
      (clf) allele, carrying a mutation in the catalytic core of PRC2, strongly
      enhanced the clf phenotype; furthermore, H3K27me3 coverage at target genes was
      strongly reduced in eol1 clf double mutants compared with clf single mutants.
      EOL1 physically interacted with CLF, its partially redundant paralog SWINGER
      (SWN), and LHP1. We propose that EOL1 interacts with LHP1-PRC2 complexes during
      replication and thereby participates in maintaining the H3K27me3 mark at target
      genes.

PMID- 28428342
TI  - Lysibodies are IgG Fc fusions with lysin binding domains targeting Staphylococcus
      aureus wall carbohydrates for effective phagocytosis.
AB  - The cell wall of Gram-positive bacteria contains abundant surface-exposed
      carbohydrate molecules that are highly conserved within and often across species.
      The potential therapeutic usefulness of high-affinity antibodies to cell wall
      carbohydrates is unquestioned, however obtaining such antibodies is challenging
      due to the poor overall immunogenicity of these bacterial targets. Autolysins and
      phage lysins are peptidoglycan hydrolases, enzymes that have evolved over a
      billion years to degrade bacterial cell wall. Such wall hydrolases are modular
      enzymes, composed of discrete domains for high-affinity binding to cell wall
      carbohydrates and cleavage activity. In this study, we demonstrate that binding
      domains from autolysins and lysins can be fused to the Fc region of human IgG,
      creating a fully functional homodimer (or "lysibody") with high-affinity binding
      and specificity for carbohydrate determinants on the bacterial surface.
      Furthermore, we demonstrate that this process is reproducible with three
      different binding domains specific to methicillin-resistant Staphylococcus aureus
      (MRSA). Cell-bound lysibodies induced the fixation of complement on the bacterial
      surface, promoted phagocytosis by macrophages and neutrophils, and protected mice
      from MRSA infection in two model systems. The lysibody approach could be used to
      target a range of difficult-to-treat pathogenic bacteria, given that cell wall
      hydrolases are ubiquitous in nature.

PMID- 28428343
TI  - Mechanisms of autophagy induction by sex steroids in bovine mammary epithelial
      cells.
AB  - In dairy cattle, mammary gland involution serves to remodel the secretory tissue
      and occurs in a period of overlap between mammogenic stimulation caused by the
      next developing pregnancy and tissue regression induced by milk stasis. At this
      time, high concentrations of 17beta-oestradiol (E2) and progesterone (P4) support
      the regeneration of the mammary tissue, as well as enhance autophagy, a cellular
      process induced in response to stressful conditions for energy generation and
      homeostasis maintenance. This study aimed to elucidate the mechanisms of
      autophagy induction by E2 and P4 using an in vitro model of involution based on
      20-fold reduction of FBS content (from 10% to 0.5%) in the culture medium of BME
      UV1 bovine mammary epithelial cells (MECs). Real-time RT-PCR, Western blot and
      EMSA analyses demonstrated that addition of E2 and P4 caused a genomic effect in
      BME-UV1 cells, stimulating the expression of autophagy-related genes (ATGs):
      BECN1, ATG5, LC3B and their corresponding proteins. Furthermore, knockdown of
      oestrogen receptor (ERalpha) and experiments with the use of oestrogen and
      progesterone antagonists (4-hydroxytamoxifen and RU-486, respectively)
      demonstrated that the observed genomic effect is mediated by steroid receptors.
      Finally, both steroids were shown to form complexes with beclin1 and regulate Bcl
      2 phosphorylation, indicating that an indirect, non-genomic effect of E2 and P4
      may also contribute to autophagy induction in bovine MECs.

PMID- 28428344
TI  - Vascular adhesion protein-1 is elevated in primary sclerosing cholangitis, is
      predictive of clinical outcome and facilitates recruitment of gut-tropic
      lymphocytes to liver in a substrate-dependent manner.
AB  - OBJECTIVE: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary
      manifestation of IBD. This clinical association is linked pathologically to the
      recruitment of mucosal T cells to the liver, via vascular adhesion protein (VAP)
      1-dependent enzyme activity. Our aim was to examine the expression, function and
      enzymatic activation of the ectoenzyme VAP-1 in patients with PSC. DESIGN: We
      examined VAP-1 expression in patients with PSC, correlated levels with clinical
      characteristics and determined the functional consequences of enzyme activation
      by specific enzyme substrates on hepatic endothelium. RESULTS: The intrahepatic
      enzyme activity of VAP-1 was elevated in PSC versus immune-mediated disease
      controls and non-diseased liver (p<0.001). The adhesion of gut-tropic
      alpha4beta7+lymphocytes to hepatic endothelial cells in vitro under flow was
      attenuated by 50% following administration of the VAP-1 inhibitor semicarbazide
      (p<0.01). Of a number of natural VAP-1 substrates tested, cysteamine-which can be
      secreted by inflamed colonic epithelium and gut bacteria-was the most efficient
      (yielded the highest enzymatic rate) and efficacious in its ability to induce
      expression of functional mucosal addressin cell adhesion molecule-1 on hepatic
      endothelium. In a prospectively evaluated patient cohort with PSC, elevated serum
      soluble (s)VAP-1 levels predicted poorer transplant-free survival for patients,
      independently (HR: 3.85, p=0.003) and additively (HR: 2.02, p=0.012) of the
      presence of liver cirrhosis. CONCLUSIONS: VAP-1 expression is increased in PSC,
      facilitates adhesion of gut-tropic lymphocytes to liver endothelium in a
      substrate-dependent manner, and elevated levels of its circulating form predict
      clinical outcome in patients.

PMID- 28428345
TI  - Proliferation of primary human hepatocytes and prevention of hepatitis B virus
      reinfection efficiently deplete nuclear cccDNA in vivo.
AB  - OBJECTIVE: The stability of the covalently closed circular DNA (cccDNA) in nuclei
      of non-dividing hepatocytes represents a key determinant of HBV persistence.
      Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover
      can reduce cccDNA loads but knowledge on the proliferative capacity of HBV
      infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in
      dividing PHHs is still lacking. This study aimed to determine the impact of human
      hepatocyte division on cccDNA stability in vivo. METHODS: PHH proliferation was
      triggered by serially transplanting hepatocytes from HBV-infected humanised mice
      into naive recipients. Cell proliferation and virological changes were assessed
      by quantitative PCR, immunofluorescence and RNA in situ hybridisation. Viral
      integrations were analysed by gel separation and deep sequencing. RESULTS: PHH
      proliferation strongly reduced all infection markers, including cccDNA (median
      2.4 log/PHH). Remarkably, cell division appeared to cause cccDNA dilution among
      daughter cells and intrahepatic cccDNA loss. Nevertheless, HBV survived in
      sporadic non-proliferating human hepatocytes, so that virological markers
      rebounded as hepatocyte expansion relented. This was due to reinfection of
      quiescent PHHs since treatment with the entry inhibitor myrcludex-B or nucleoside
      analogues blocked viral spread and intrahepatic cccDNA accumulation. Viral
      integrations were detected both in donors and recipient mice but did not appear
      to contribute to antigen production. CONCLUSIONS: We demonstrate that human
      hepatocyte division even without involvement of cytolytic mechanisms triggers
      substantial cccDNA loss. This process may be fundamental to resolve self-limiting
      acute infection and should be considered in future therapeutic interventions
      along with entry inhibition strategies.

PMID- 28428346
TI  - Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and
      Dementia: A Prospective Cohort Study.
AB  - BACKGROUND AND PURPOSE: Sugar- and artificially-sweetened beverage intake have
      been linked to cardiometabolic risk factors, which increase the risk of
      cerebrovascular disease and dementia. We examined whether sugar- or artificially
      sweetened beverage consumption was associated with the prospective risks of
      incident stroke or dementia in the community-based Framingham Heart Study
      Offspring cohort. METHODS: We studied 2888 participants aged >45 years for
      incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged
      >60 years for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage
      intake was quantified using a food-frequency questionnaire at cohort examinations
      5 (1991-1995), 6 (1995-1998), and 7 (1998-2001). We quantified recent consumption
      at examination 7 and cumulative consumption by averaging across examinations.
      Surveillance for incident events commenced at examination 7 and continued for 10
      years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of
      incident dementia (63 consistent with Alzheimer's disease). RESULTS: After
      adjustments for age, sex, education (for analysis of dementia), caloric intake,
      diet quality, physical activity, and smoking, higher recent and higher cumulative
      intake of artificially sweetened soft drinks were associated with an increased
      risk of ischemic stroke, all-cause dementia, and Alzheimer's disease dementia.
      When comparing daily cumulative intake to 0 per week (reference), the hazard
      ratios were 2.96 (95% confidence interval, 1.26-6.97) for ischemic stroke and
      2.89 (95% confidence interval, 1.18-7.07) for Alzheimer's disease. Sugar
      sweetened beverages were not associated with stroke or dementia. CONCLUSIONS:
      Artificially sweetened soft drink consumption was associated with a higher risk
      of stroke and dementia.

PMID- 28428347
TI  - Sugar-Sweetened and Artificially Sweetened Beverages in Relation to Stroke and
      Dementia: Are Soft Drinks Hard on the Brain?

PMID- 28428348
TI  - Predictors of the Aspiration Component Success of a Direct Aspiration First Pass
      Technique (ADAPT) for the Endovascular Treatment of Stroke Reperfusion Strategy
      in Anterior Circulation Acute Stroke.
AB  - BACKGROUND AND PURPOSE: A direct aspiration first pass technique (ADAPT) has been
      reported to be fast, safe, and effective for the treatment of acute ischemic
      stroke. The aim of this study is to determine the preoperative factors that
      affect success of the aspiration component of the technique in ischemic stroke
      patients with large vessel occlusion in the anterior circulation. METHODS: We
      enrolled all 347 consecutive patients with anterior circulation acute ischemic
      stroke admitted for mechanical thrombectomy at our institution from August 2013
      to October 2015 and treated by ADAPT for the endovascular treatment of stroke.
      Baseline and procedural characteristics, modified thrombolysis in cerebral
      infarction scores, and 3-month modified Rankin Scale were captured and analyzed.
      RESULTS: Among the 347 patients (occlusion sites: middle cerebral artery=200,
      58%; internal carotid artery Siphon=89, 25%; Tandem=58, 17%), aspiration
      component led to successful reperfusion (modified thrombolysis in cerebral
      infarction 2b/3 scores) in 55.6% (193/347 patients), stent retrievers were
      required in 40%, and a total successful final reperfusion rate of 83% (288/347)
      was achieved. Overall, procedural complications occurred in 13.3% of patients
      (48/347). Modified Rankin Scale score of 0 to 2 at 90 days was reported in 45%
      (144/323). Only 2 factors positively influenced the success of the aspiration
      component: an isolated middle cerebral artery occlusion (P<0.001) and a shorter
      time from stroke onset to clot contact (P=0.018). CONCLUSIONS: In this large
      retrospective study, ADAPT was shown to be safe and effective for anterior
      circulation acute ischemic stroke with a final successful reperfusion achieved in
      83%. The site of arterial occlusion and delay of the procedure were predictors
      for reperfusion. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT02523261, NCT02678169, and NCT02466893.

PMID- 28428349
TI  - Toll-Like Receptor 4 Mediates Hemorrhagic Transformation After Delayed Tissue
      Plasminogen Activator Administration in In Situ Thromboembolic Stroke.
AB  - BACKGROUND AND PURPOSE: Hemorrhagic transformation is the main complication of
      revascularization therapies after stroke. Toll-like receptor 4 (TLR4) is
      implicated in cerebral damage and inflammation in stroke. This study was designed
      to determine the role of TLR4 in hemorrhagic transformation development after
      tissue plasminogen activator (tPA) administration. METHODS: Mice expressing
      (TLR4+/+) or lacking functional TLR4 (TLR4-/-) were subjected to middle cerebral
      artery occlusion using an in situ thromboembolic model by thrombin injection into
      the middle cerebral artery, and tPA (10 mg/kg) was administered 20 minutes or 3
      hours after ischemia. Infarct size, hemorrhages, IgG extravasation, matrix
      metalloproteinase 9 expression, and neutrophil infiltration were assessed 24
      hours after ischemia. RESULTS: In TLR4+/+, early reperfusion (tPA at 20 minutes)
      resulted infarct volume, whereas late recanalization (tPA at 3 hours) did not
      modify lesion size and increased the rate of the most severe hemorrhages. In TLR4
      /- mice, both early and late reperfusion did not modify lesion size. Importantly,
      late tPA administration did not result in worse hemorrhages and in an increased
      bleeding area as occurred in TLR4+/+ group. In TLR4-/- animals, late reperfusion
      produced a lesser increase in matrix metalloproteinase 9 expression when compared
      with TLR4+/+ animals. CONCLUSIONS: Our results demonstrate TLR4 involvement in
      hemorrhagic transformation induced by delayed tPA administration, very likely by
      increasing matrix metalloproteinase 9 expression.

PMID- 28428351
TI  - Medical charity will help GPs defy government's immigration crackdown.

PMID- 28428350
TI  - Targeted inactivation of copper transporter Atp7b in hepatocytes causes liver
      steatosis and obesity in mice.
AB  - Copper-transporting ATPase 2 (ATP7B) is essential for mammalian copper
      homeostasis. Mutations in ATP7B result in copper accumulation, especially in the
      liver, and cause Wilson disease (WD). The major role of hepatocytes in WD
      pathology is firmly established. It is less certain whether the excess Cu in
      hepatocytes is solely responsible for development of WD. To address this issue,
      we generated a mouse strain for Cre-mediated deletion of Atp7b and inactivated
      Atp7b selectively in hepatocytes. Atp7bDeltaHep mice accumulate copper in the
      liver, have elevated urinary copper, and lack holoceruloplasmin but show no liver
      disease for up to 30 wk. Liver inflammation is muted and markedly delayed
      compared with the age-matched Atp7b-/- null mice, which show a strong type1
      inflammatory response. Expression of metallothioneins is higher in Atp7bDeltaHep
      livers than in Atp7b-/- mice, suggesting better sequestration of excess copper.
      Characterization of purified cell populations also revealed that nonparenchymal
      cells in Atp7bDeltaHep liver maintain Atp7b expression, have normal copper
      balance, and remain largely quiescent. The lack of inflammation unmasked
      metabolic consequences of copper misbalance in hepatocytes. Atp7bDeltaHep animals
      weigh more than controls and have higher levels of liver triglycerides and 3
      hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. By 45 wk, all animals develop
      liver steatosis on a regular diet. Thus copper misbalance in hepatocytes
      dysregulates lipid metabolism, whereas development of inflammatory response in WD
      may depend on copper status of nonparenchymal cells. The implications of these
      findings for the cell-targeting WD therapies are discussed.NEW & NOTEWORTHY
      Targeted inactivation of copper-transporting ATPase 2 (Atp7b) in hepatocytes
      causes steatosis in the absence of inflammation.

PMID- 28428352
TI  - Thrombin-Mediated Degradation of Human Cardiac Troponin T.
AB  - BACKGROUND: Cardiac troponin T (cTnT) is an acknowledged biomarker of acute
      myocardial infarction (AMI) that is known to be prone to proteolytic degradation
      in serum. Such degradation is usually explained by the action of MU-calpain,
      although there could be other candidates for that role. In the current study, we
      explored the hypothesis that thrombin-mediated cTnT cleavage occurs as a result
      of the serum sample preparation. METHODS: cTnT degradation was studied by using
      immunoblotting and mass spectrometry (MS) analysis. RESULTS: The comparison of
      cTnT isolated from AMI heparin plasma and serum samples showed that cTnT in the
      plasma samples was mainly present as the full-sized molecule (approximately 35
      kDa), while in serum samples it was present as a 29-kDa fragment. The incubation
      of recombinant cTnT, or native ternary cardiac troponin complex with thrombin or
      in normal human serum (NHS), resulted in the formation of a 29-kDa product that
      was similar to that detected in AMI serum samples. No cTnT degradation was
      observed when thrombin or NHS was pretreated with hirudin, a specific inhibitor
      of thrombin, or during incubation of troponin in normal heparin plasma. When the
      products of thrombin-mediated cTnT proteolysis were analyzed by MS, 2 fragments
      consisting of amino acid residues (aar) 2-68 and 69-288 were identified, which
      suggests that thrombin cleaves cTnT between R68 and S69. CONCLUSIONS: The results
      of this study suggest that the 29-kDa fragment of cTnT in AMI serum samples
      mainly appears due to the cleavage by thrombin during serum sample preparation.

PMID- 28428353
TI  - Development of a BNP1-32 Immunoassay That Does Not Cross-React with proBNP.
AB  - BACKGROUND: Plasma B-type natriuretic peptide (BNP) concentration reflects
      cardiac dysfunction and assists in determining the diagnosis and prognosis of
      heart failure (HF). Current BNP assays overestimate circulating bioactive BNP1-32
      concentrations as they also detect less active BNP metabolites and proBNP. A
      specific BNP1-32 assay with negligible cross-reactivity to proBNP and/or BNP
      metabolites may be advantageous. METHODS: We developed a Luminex-based specific
      BNP1-32 immunoassay and compared results obtained from 3 other BNP assays (a
      Luminex-based total-BNP assay, our BNP RIA, and the commercially available Abbott
      Architect BNP assay) in plasma from 42 patients with HF and 22 healthy controls.
      RESULTS: The BNP1-32 assay showed 57% cross-reactivity with BNP2-32, but <=0.1%
      cross-reactivity to BNP3-32, other BNP metabolites, and proBNP; its detection
      limit was 0.35 ng/L; and intra- and interassay CVs were <15%. BNP
      immunoreactivity increased with HF severity (median concentrations being 0.3,
      0.8, 26.2, and 17.3 ng/L in healthy controls and 40.7, 139, 465, and 1778 ng/L in
      HF patients for the BNP1-32, total-BNP, BNP RIA, and Abbott BNP assays
      respectively). The fold increase between HF cases with the New York Heart
      Association (NYHA) class IV was significantly greater with the BNP1-32 assay than
      the Abbott BNP (P = 0.026) and the BNP RIA (P < 0.0001) but not the total-BNP
      assay. CONCLUSIONS: We have developed the first assay that measures BNP1-32 in
      plasma without interference by proBNP. Analysis of larger patient cohorts is now
      required to compare the performance of this assay with current less specific
      assays for the diagnosis or prognosis of HF.

PMID- 28428355
TI  - Plasma Urate, Cancer Incidence, and All-Cause Mortality: A Mendelian
      Randomization Study.
AB  - BACKGROUND: Observationally, high plasma urate is associated with high risk of
      cancer. We used a Mendelian randomization design to test the hypothesis that high
      concentrations of plasma urate are associated with high cancer incidence and all
      cause mortality observationally and genetically. METHODS: We performed
      observational and genetic analyses using plasma urate and the urate solute
      carrier family 2 member 9 (SLC2A9) rs7442295 genotype in 86210 individuals from
      the Copenhagen General Population Study. Cancer and mortality end points were
      from national cancer and death registries. Incidences and risk of cancer and all
      cause mortality were calculated using Cox regression, Fine and Gray competing
      risks regression, and instrumental variable analyses. RESULTS: During a median
      follow-up time of 3.9 years for cancer and 4.9 years for all-cause mortality,
      3243 individuals received a diagnosis of cancer and 3978 died. Observationally,
      50% higher plasma urate was associated with multivariable-adjusted hazard ratios
      of 1.11 (95% CI, 1.05-1.18) for cancer incidence and 1.07 (1.01-1.13) for all
      cause mortality. Each A-allele of the SLC2A9 rs7442295 was associated with 9%
      higher plasma urate and hazard ratios of 1.07 (1.01-1.14) for cancer incidence
      and 1.07 (1.02-1.13) for all-cause mortality. In instrumental variable analyses,
      the odds ratios for a genetically determined 50% higher plasma urate was 1.22
      (1.02-1.47) for cancer incidence and 1.49 (1.13-1.93) for all-cause mortality.
      CONCLUSIONS: High plasma urate was both observationally and genetically
      associated with high cancer incidence and high all-cause mortality, suggesting
      causal relationships.

PMID- 28428354
TI  - Multiplex Tandem Mass Spectrometry Enzymatic Activity Assay for Newborn Screening
      of the Mucopolysaccharidoses and Type 2 Neuronal Ceroid Lipofuscinosis.
AB  - BACKGROUND: We expanded the use of tandem mass spectrometry combined with liquid
      chromatography (LC-MS/MS) for multiplex newborn screening of seven lysosomal
      enzymes in dried blood spots (DBS). The new assays are for enzymes responsible
      for the mucopolysaccharidoses (MPS-I, -II, -IIIB, -IVA, -VI, and -VII) and type 2
      neuronal ceroid lipofuscinosis (LINCL). METHODS: New substrates were prepared and
      characterized for tripeptidyl peptidase 1 (TPP1), alpha-N-acetylglucosaminidase
      (NAGLU), and lysosomal beta-glucuronidase (GUSB). These assays were combined with
      previously developed assays to provide a multiplex LC-MS/MS assay of 7 lysosomal
      storage diseases. Multiple reaction monitoring of ion dissociations for enzyme
      products and deuterium-labeled internal standards was used to quantify the enzyme
      activities. RESULTS: Deidentified DBS samples from 62 nonaffected newborns were
      analyzed to simultaneously determine (run time 2 min per DBS) the activities of
      TPP1, NAGLU, and GUSB, along with those for alpha-iduronidase (IDUA), iduronate-2
      sulfatase (I2S), N-acetylgalactosamine-6-sulfatase (GALNS), and N
      acetylgalactosamine-4-sulfatase (ARSB). The activities measured in the 7-plex
      format showed assay response-to-blank-activity ratios (analytical ranges) of 102
      909 that clearly separated healthy infants from affected children. CONCLUSIONS:
      The new multiplex assay provides a robust comprehensive newborn screening assay
      for the mucopolysaccharidoses. The method has been expanded to include additional
      lysosomal storage diseases.

PMID- 28428357
TI  - A Critical Appraisal of the Recent IFCC Statements on Cardiac Troponin Assays.

PMID- 28428356
TI  - Biological Variation Estimates Obtained from 91 Healthy Study Participants for 9
      Enzymes in Serum.
AB  - BACKGROUND: We sought to develop estimates of biological variation (BV) for 9
      enzymes in blood serum as part of the European Biological Variation Study.
      METHODS: Ninety-one healthy study participants (38 male and 53 female, 21-69
      years old) were phlebotomized in each of 10 consecutive weeks at 6 European
      laboratories. The same preanalytical sample-handling protocol was followed at
      each center before transport to San Raffaele Hospital, Milan, Italy, for
      analysis. Sera were stored at -80  degrees C before analysis in duplicate within
      a single run on an ADVIA 2400 Clinical Chemistry System (Siemens Healthcare)
      following a protocol designed to minimize analytical imprecision. Assay
      traceability was established using frozen sera with target values assigned by
      reference methods. The results were subjected to outlier analysis before CV-ANOVA
      to deliver valid BV estimates. Results for 9 enzymes were subsequently
      partitioned for graphical display allowing visual assessment of the effects of
      country of origin, sex, and age on BV estimates. RESULTS: We found no effect of
      country upon the observed variation, but overall sex-related differences were
      evident for alanine amino transferase (ALT), gamma-glutamyl transferase (GGT),
      and creatine kinase (CK). The following estimates for within-subject BV (CVI) and
      between-subject BV (CVG), respectively, were obtained: ALT: 9.3%, 28.2%;
      aspartate aminotransferase: 9.5%, 20.3%; GGT: 8.9%, 41.7%; alkaline phosphatase :
      5.3%, 24.9%; lactate dehydrogenase: 5.2%, 12.6%; CK: 14.5%, 31.5%; amylase: 6.8%,
      30.4%; pancreatic alpha-amylase: 6.3%, 24.9%; and lipase (LIP): 7.7%, 23.8%.
      CONCLUSIONS: All CVI and some CVG estimates were lower than those reported in the
      online BV 2014 updated database. Analytical performance specifications derived
      from BV can be applied internationally.

PMID- 28428358
TI  - Effect of Repeat Measurements of High-Sensitivity Cardiac Troponin on the Same
      Sample Using the European Society of Cardiology 0-Hour/1-Hour or 2-Hour
      Algorithms for Early Rule-Out and Rule-In for Myocardial Infarction.

PMID- 28428359
TI  - In Reply.

PMID- 28428360
TI  - Cardiac Troponins: Molecules of Many Surprises.

PMID- 28428361
TI  - Single-Tube Dodecaplex PCR Panel of Polymorphic Microsatellite Markers Closely
      Linked to the DMPK CTG Repeat for Preimplantation Genetic Diagnosis of Myotonic
      Dystrophy Type 1.
AB  - BACKGROUND: Preimplantation genetic diagnosis (PGD) of myotonic dystrophy type 1
      (DM1) currently uses conventional PCR to detect nonexpanded dystrophia myotonica
      protein kinase (DMPK) alleles or triplet-primed PCR to detect the CTG-expanded
      alleles, coupled with analysis of linked microsatellite markers to increase
      diagnostic accuracy. We aimed to simplify the process of identification and
      selection of informative linked markers for application to DM1 PGD. METHODS: An
      in silico search was performed to identify all markers within 1-1.5 Mb flanking
      the DMPK gene. Five previously known (D19S559, APOC2, D19S543, D19S112, and
      BV209569) and 7 novel (DM45050, DM45178, DM45209, DM45958, DM46513, DM46892, and
      DM47004.1) markers with potentially high heterozygosity values and polymorphism
      information content were selected and optimized in a single-tube multiplex PCR
      panel. RESULTS: Analysis of 184 DNA samples of Chinese and Caucasian individuals
      (91 from unrelated, anonymized cord blood of Chinese babies born at the National
      University Hospital, Singapore, and 93 Caucasian DNA samples from the Human
      Variation Panel HD100CAU) confirmed the high polymorphism indices of all markers
      (polymorphism information content >0.5), with observed heterozygosity values
      ranging from 0.62-0.93. All individuals were heterozygous for at least 6 markers,
      with 99.5% of individuals heterozygous for at least 2 markers on either side of
      the DMPK CTG repeat. The dodecaplex marker assay was successfully validated on 42
      single cells and 12 whole genome amplified single cells. CONCLUSIONS: The DM1
      multiplex PCR panel is suitable for use in DM1 PGD either as a standalone linkage
      based assay or as a complement to DMPK CTG repeat expansion-mutation detection.

PMID- 28428362
TI  - Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory
      hormones.
AB  - Fatty liver can be diet, endocrine, drug, virus or genetically induced.
      Independent of cause, hepatic lipid accumulation promotes systemic metabolic
      dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR)
      ligands, hepatic non-esterified fatty acids upregulate expression of
      gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting
      hyperglycemia, hyperlipidemia and ketosis. The typical hormonal environment in
      fatty liver disease consists of hyperinsulinemia, hyperglucagonemia,
      hypercortisolemia, growth hormone deficiency and elevated sympathetic tone. These
      endocrine and metabolic changes further encourage hepatic steatosis by regulating
      adipose tissue lipolysis, liver lipid uptake, de novo lipogenesis (DNL), beta
      oxidation, ketogenesis and lipid export. Hepatic lipid accumulation may be
      induced by 4 separate mechanisms: (1) increased hepatic uptake of circulating
      fatty acids, (2) increased hepatic de novo fatty acid synthesis, (3) decreased
      hepatic beta-oxidation and (4) decreased hepatic lipid export. This review will
      discuss the hormonal regulation of each mechanism comparing multiple
      physiological models of hepatic lipid accumulation. Nonalcoholic fatty liver
      disease (NAFLD) is typified by increased hepatic lipid uptake, synthesis,
      oxidation and export. Chronic hepatic lipid signaling through PPARgamma results
      in gene expression changes that allow concurrent activity of DNL and beta
      oxidation. The importance of hepatic steatosis in driving systemic metabolic
      dysfunction is highlighted by the common endocrine and metabolic disturbances
      across many conditions that result in fatty liver. Understanding the mechanisms
      underlying the metabolic dysfunction that develops as a consequence of hepatic
      lipid accumulation is critical to identifying points of intervention in this
      increasingly prevalent disease state.

PMID- 28428363
TI  - PHLPP: a putative cellular target during insulin resistance and type 2 diabetes.
AB  - Progressive research in the past decade converges to the impact of PHLPP in
      regulating the cellular metabolism through PI3K/AKT inhibition. Aberrations in
      PKB/AKT signaling coordinates with impaired insulin secretion and insulin
      resistance, identified during T2D, obesity and cardiovascular disorders which
      brings in the relevance of PHLPPs in the metabolic paradigm. In this review, we
      discuss the impact of PHLPP isoforms in insulin signaling and its associated
      cellular events including mitochondrial dysfunction, DNA damage, autophagy and
      cell death. The article highlights the plausible molecular targets that share the
      role during insulin-resistant states, whose understanding can be extended into
      treatment responses to facilitate targeted drug discovery for T2D and allied
      metabolic syndromes.

PMID- 28428364
TI  - Role of estrogen receptor signaling in skeletal response to leptin in female
      ob/ob mice.
AB  - Leptin, critical in regulation of energy metabolism, is also important for normal
      bone growth, maturation and turnover. Compared to wild type (WT) mice, bone mass
      is lower in leptin-deficient ob/ob mice. Osteopenia in growing ob/ob mice is due
      to decreased bone accrual, and is associated with reduced longitudinal bone
      growth, impaired cancellous bone maturation and increased marrow adipose tissue
      (MAT). However, leptin deficiency also results in gonadal dysfunction, disrupting
      production of gonadal hormones which regulate bone growth and turnover. The
      present study evaluated the role of increased estrogen in mediating the effects
      of leptin on bone in ob/ob mice. Three-month-old female ob/ob mice were
      randomized into one of the 3 groups: (1) ob/ob + vehicle (veh), (2) ob/ob +
      leptin (leptin) or (3) ob/ob + leptin and the potent estrogen receptor antagonist
      ICI 182,780 (leptin + ICI). Age-matched WT mice received vehicle. Leptin (40
      ug/mouse, daily) and ICI (10 ug/mouse, 2*/week) were administered by subcutaneous
      injection for 1 month and bone analyzed by X-ray absorptiometry, microcomputed
      tomography and static and dynamic histomorphometry. Uterine weight did not differ
      between ob/ob mice and ob/ob mice receiving leptin + ICI, indicating that ICI
      successfully blocked the uterine response to leptin-induced increases in estrogen
      levels. Compared to leptin-treated ob/ob mice, ob/ob mice receiving leptin + ICI
      had lower uterine weight; did not differ in weight loss, MAT or bone formation
      rate; and had higher longitudinal bone growth rate and cancellous bone volume
      fraction. We conclude that increased estrogen signaling following leptin
      treatment is dispensable for the positive actions of leptin on bone and may
      attenuate leptin-induced bone growth.

PMID- 28428365
TI  - Interaction and Transport of Methamphetamine and its Primary Metabolites by
      Organic Cation and Multidrug and Toxin Extrusion Transporters.
AB  - Methamphetamine is one of the most abused illicit drugs with roughly 1.2 million
      users in the United States alone. A large portion of methamphetamine and its
      metabolites is eliminated by the kidney with renal clearance larger than
      glomerular filtration clearance. Yet the mechanism of active renal secretion is
      poorly understood. The goals of this study were to characterize the interaction
      of methamphetamine and its major metabolites with organic cation transporters
      (OCTs) and multidrug and toxin extrusion (MATE) transporters and to identify the
      major transporters involved in the disposition of methamphetamine and its major
      metabolites, amphetamine and para-hydroxymethamphetamine (p-OHMA). We used cell
      lines stably expressing relevant transporters to show that methamphetamine and
      its metabolites inhibit human OCTs 1-3 (hOCT1-3) and hMATE1/2-K with the greatest
      potencies against hOCT1 and hOCT2. Methamphetamine and amphetamine are substrates
      of hOCT2, hMATE1, and hMATE2-K, but not hOCT1 and hOCT3. p-OHMA is transported by
      hOCT1-3 and hMATE1, but not hMATE2-K. In contrast, organic anion transporters 1
      and 3 do not interact with or transport these compounds. Methamphetamine and its
      metabolites exhibited complex interactions with hOCT1 and hOCT2, suggesting the
      existence of multiple binding sites. Our studies suggest the involvement of the
      renal OCT2/MATE pathway in tubular secretion of methamphetamine and its major
      metabolites and the potential of drug-drug interactions with substrates or
      inhibitors of the OCTs. This information may be considered when prescribing
      medications to suspected or known abusers of methamphetamine to mitigate the risk
      of increased toxicity or reduced therapeutic efficacy.

PMID- 28428366
TI  - In Vitro Metabolism of Oprozomib, an Oral Proteasome Inhibitor: Role of Epoxide
      Hydrolases and Cytochrome P450s.
AB  - Oprozomib is an oral proteasome inhibitor currently under investigation in
      patients with hematologic malignancies or solid tumors. Oprozomib elicits potent
      pharmacological actions by forming a covalent bond with the active site N
      terminal threonine of the 20S proteasome. Oprozomib has a short half-life across
      preclinical species and in patients due to systemic clearance via metabolism.
      Potential for drug-drug interactions (DDIs) could alter the exposure of this
      potent therapeutic; therefore, a thorough investigation of pathways responsible
      for metabolism is required. In the present study, the major drug-metabolizing
      enzyme responsible for oprozomib metabolism was identified in vitro. A diol of
      oprozomib was found to be the predominant metabolite in human hepatocytes, which
      formed via direct epoxide hydrolysis. Using recombinant epoxide hydrolases (EHs)
      and selective EH inhibitors in liver microsomes, microsomal EH (mEH) but not
      soluble EH (sEH) was found to be responsible for oprozomib diol formation.
      Coincubation with 2-nonylsulfanyl-propionamide, a selective mEH inhibitor,
      resulted in a significant decrease in oprozomib disappearance (>80%) with
      concurrent complete blockage of diol formation in human hepatocytes. On the
      contrary, a selective sEH inhibitor did not affect oprozomib metabolism.
      Pretreatment of hepatocytes with the pan-cytochrome P450 (P450) inhibitor 1
      aminobenzotriazole resulted in a modest reduction (~20%) of oprozomib metabolism.
      These findings indicated that mEH plays a predominant role in oprozomib
      metabolism. Further studies may be warranted to determine whether drugs that are
      mEH inhibitors cause clinically significant DDIs with oprozomib. On the other
      hand, pharmacokinetics of oprozomib is unlikely to be affected by coadministered
      P450 and sEH inhibitors and/or inducers.

PMID- 28428368
TI  - Erratum. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of
      Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on
      Basal Insulin and Metformin: The LixiLan-L Randomized Trial. Diabetes Care
      2016;39:1972-1980.

PMID- 28428367
TI  - COPII-coated membranes function as transport carriers of intracellular
      procollagen I.
AB  - The coat protein complex II (COPII) is essential for the transport of large
      cargo, such as 300-nm procollagen I (PC1) molecules, from the endoplasmic
      reticulum (ER) to the Golgi. Previous work has shown that the CUL3-KLHL12 complex
      increases the size of COPII vesicles at ER exit sites to more than 300 nm in
      diameter and accelerates the secretion of PC1. However, the role of large COPII
      vesicles as PC1 transport carriers was not unambiguously demonstrated. In this
      study, using stochastic optical reconstruction microscopy, correlated light
      electron microscopy, and live-cell imaging, we demonstrate the existence of
      mobile COPII-coated vesicles that completely encapsulate the cargo PC1 and are
      physically separated from ER. We also developed a cell-free COPII vesicle budding
      reaction that reconstitutes the capture of PC1 into large COPII vesicles. This
      process requires COPII proteins and the GTPase activity of the COPII subunit
      SAR1. We conclude that large COPII vesicles are bona fide carriers of PC1.

PMID- 28428371
TI  - News at a glance.

PMID- 28428370
TI  - Why Earth Optimism?

PMID- 28428372
TI  - In familiar decays, a whiff of new physics.

PMID- 28428369
TI  - Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes,
      and progenitors.
AB  - Dendritic cells (DCs) and monocytes play a central role in pathogen sensing,
      phagocytosis, and antigen presentation and consist of multiple specialized
      subtypes. However, their identities and interrelationships are not fully
      understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells,
      we identified six human DCs and four monocyte subtypes in human blood. Our study
      reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but
      potently activates T cells, thus redefining pDCs; a new subdivision within the
      CD1C+ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia
      cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our
      revised taxonomy will enable more accurate functional and developmental analyses
      as well as immune monitoring in health and disease.

PMID- 28428373
TI  - Early animal fossils at risk.

PMID- 28428374
TI  - A moonshot for chemistry.

PMID- 28428375
TI  - A new neglected crop: cannabis.

PMID- 28428376
TI  - Society labels harassment as research misconduct.

PMID- 28428377
TI  - Scientists hope risky winter voyage yields icy rewards.

PMID- 28428378
TI  - Lord of the rings.

PMID- 28428379
TI  - Sam Ting's last tease.

PMID- 28428380
TI  - Facilitating conservation.

PMID- 28428381
TI  - Oxidation at the atomic scale.

PMID- 28428382
TI  - Lasers expose hidden electronic order.

PMID- 28428383
TI  - Biased inheritance protects older bacteria from harm.

PMID- 28428384
TI  - Rewiring metabolism under oxygen deprivation.

PMID- 28428385
TI  - Decoding hormones for a stem cell niche.

PMID- 28428386
TI  - Living by the lessons of the planet.

PMID- 28428388
TI  - Culture clash.

PMID- 28428387
TI  - Putting a value on injuries to natural assets: The BP oil spill.

PMID- 28428389
TI  - Dramatizing Deepwater Horizon.

PMID- 28428390
TI  - Ecosystem Earth.

PMID- 28428391
TI  - The interaction of human population, food production, and biodiversity
      protection.
AB  - Research suggests that the scale of human population and the current pace of its
      growth contribute substantially to the loss of biological diversity. Although
      technological change and unequal consumption inextricably mingle with demographic
      impacts on the environment, the needs of all human beings-especially for food
      imply that projected population growth will undermine protection of the natural
      world. Numerous solutions have been proposed to boost food production while
      protecting biodiversity, but alone these proposals are unlikely to staunch
      biodiversity loss. An important approach to sustaining biodiversity and human
      well-being is through actions that can slow and eventually reverse population
      growth: investing in universal access to reproductive health services and
      contraceptive technologies, advancing women's education, and achieving gender
      equality.

PMID- 28428392
TI  - Ecosystem management as a wicked problem.
AB  - Ecosystems are self-regulating systems that provide societies with food, water,
      timber, and other resources. As demands for resources increase, management
      decisions are replacing self-regulating properties. Counter to previous technical
      approaches that applied simple formulas to estimate sustainable yields of single
      species, current research recognizes the inherent complexity of ecosystems and
      the inability to foresee all consequences of interventions across different
      spatial, temporal, and administrative scales. Ecosystem management is thus more
      realistically seen as a "wicked problem" that has no clear-cut solution.
      Approaches for addressing such problems include multisector decision-making,
      institutions that enable management to span across administrative boundaries,
      adaptive management, markets that incorporate natural capital, and collaborative
      processes to engage diverse stakeholders and address inequalities. Ecosystem
      management must avoid two traps: falsely assuming a tame solution and inaction
      from overwhelming complexity. An incremental approach can help to avoid these
      traps.

PMID- 28428395
TI  - Losing its character.

PMID- 28428393
TI  - Biodiversity losses and conservation responses in the Anthropocene.
AB  - Biodiversity is essential to human well-being, but people have been reducing
      biodiversity throughout human history. Loss of species and degradation of
      ecosystems are likely to further accelerate in the coming years. Our
      understanding of this crisis is now clear, and world leaders have pledged to
      avert it. Nonetheless, global goals to reduce the rate of biodiversity loss have
      mostly not been achieved. However, many examples of conservation success show
      that losses can be halted and even reversed. Building on these lessons to turn
      the tide of biodiversity loss will require bold and innovative action to
      transform historical relationships between human populations and nature.

PMID- 28428394
TI  - Beyond the roots of human inaction: Fostering collective effort toward ecosystem
      conservation.
AB  - The term "environmental problem" exposes a fundamental misconception: Disruptions
      of Earth's ecosystems are at their root a human behavior problem. Psychology is a
      potent tool for understanding the external and internal drivers of human behavior
      that lead to unsustainable living. Psychologists already contribute to individual
      level behavior-change campaigns in the service of sustainability, but attention
      is turning toward understanding and facilitating the role of individuals in
      collective and collaborative actions that will modify the environmentally
      damaging systems in which humans are embedded. Especially crucial in moving
      toward long-term human and environmental well-being are transformational
      individuals who step outside of the norm, embrace ecological principles, and
      inspire collective action. Particularly in developed countries, fostering legions
      of sustainability leaders rests upon a fundamental renewal of humans' connection
      to the natural world.

PMID- 28428396
TI  - Capturing chemokines in chronic wounds.

PMID- 28428397
TI  - Multiple images of a type Ia supernova.

PMID- 28428398
TI  - Low-temperature methane reactions.

PMID- 28428399
TI  - Gut anaerobes protect against pathogen invasion.

PMID- 28428400
TI  - Safe anaerobic metabolism.

PMID- 28428401
TI  - Ancestral legacy effects.

PMID- 28428402
TI  - Micromanaging muscle cell fusion.

PMID- 28428403
TI  - Resident memory responses to cancer.

PMID- 28428404
TI  - What's in a drop of blood?

PMID- 28428405
TI  - Acetylation keeps microtubules strong.

PMID- 28428406
TI  - Double duty for mammary stem cell niche.

PMID- 28428407
TI  - Watching nanomaterials transform in time.

PMID- 28428408
TI  - Drug efflux machinery inherited asymmetrically.

PMID- 28428409
TI  - Humans-an overwhelming force?

PMID- 28428410
TI  - A transcription factor drug for asthma.

PMID- 28428411
TI  - A nonlinear peek into electronic symmetry.

PMID- 28428412
TI  - Facilitating refuges.

PMID- 28428413
TI  - Countering chemo's effects on fertility.

PMID- 28428414
TI  - The physics of social butterflies.

PMID- 28428415
TI  - The eyes have it.

PMID- 28428416
TI  - Disordered proteins make a dynamic switch.

PMID- 28428417
TI  - Setting up a recruiting office.

PMID- 28428418
TI  - Nanostructured high-strength alloys.

PMID- 28428420
TI  - A parity-breaking electronic nematic phase transition in the spin-orbit coupled
      metal Cd2Re2O7.
AB  - Strong electron interactions can drive metallic systems toward a variety of well
      known symmetry-broken phases, but the instabilities of correlated metals with
      strong spin-orbit coupling have only recently begun to be explored. We uncovered
      a multipolar nematic phase of matter in the metallic pyrochlore Cd2Re2O7 using
      spatially resolved second-harmonic optical anisotropy measurements. Like
      previously discovered electronic nematic phases, this multipolar phase
      spontaneously breaks rotational symmetry while preserving translational
      invariance. However, it has the distinguishing property of being odd under
      spatial inversion, which is allowed only in the presence of spin-orbit coupling.
      By examining the critical behavior of the multipolar nematic order parameter, we
      show that it drives the thermal phase transition near 200 kelvin in Cd2Re2O7 and
      induces a parity-breaking lattice distortion as a secondary order.

PMID- 28428419
TI  - iPTF16geu: A multiply imaged, gravitationally lensed type Ia supernova.
AB  - We report the discovery of a multiply imaged, gravitationally lensed type Ia
      supernova, iPTF16geu (SN 2016geu), at redshift z = 0.409. This phenomenon was
      identified because the light from the stellar explosion was magnified more than
      50 times by the curvature of space around matter in an intervening galaxy. We
      used high-spatial-resolution observations to resolve four images of the lensed
      supernova, approximately 0.3 arc seconds from the center of the foreground
      galaxy. The observations probe a physical scale of ~1 kiloparsec, smaller than is
      typical in other studies of extragalactic gravitational lensing. The large
      magnification and symmetric image configuration imply close alignment between the
      lines of sight to the supernova and to the lens. The relative magnifications of
      the four images provide evidence for substructures in the lensing galaxy.

PMID- 28428421
TI  - Low-temperature activation of methane on the IrO2(110) surface.
AB  - Methane undergoes highly facile C-H bond cleavage on the stoichiometric IrO2(110)
      surface. From temperature-programmed reaction spectroscopy experiments, we found
      that methane molecularly adsorbed as a strongly bound sigma complex on IrO2(110)
      and that a large fraction of the adsorbed complexes underwent C-H bond cleavage
      at temperatures as low as 150 kelvin (K). The initial dissociation probability of
      methane on IrO2(110) decreased from 80 to 20% with increasing surface temperature
      from 175 to 300 K. We estimate that the activation energy for methane C-H bond
      cleavage is 9.5 kilojoule per mole (kJ/mol) lower than the binding energy of the
      adsorbed precursor on IrO2(110), and equal to a value of ~28.5 kJ/mol. Low
      temperature activation may avoid unwanted side reactions in the development of
      catalytic processes to selectively convert methane to value-added products.

PMID- 28428422
TI  - Quantitative 3D evolution of colloidal nanoparticle oxidation in solution.
AB  - Real-time tracking of the three-dimensional (3D) evolution of colloidal
      nanoparticles in solution is essential for understanding complex mechanisms
      involved in nanoparticle growth and transformation. We used time-resolved small
      angle and wide-angle x-ray scattering simultaneously to monitor oxidation of
      highly uniform colloidal iron nanoparticles, enabling the reconstruction of
      intermediate 3D morphologies of the nanoparticles with a spatial resolution of ~5
      angstroms. The in situ observations, combined with large-scale reactive molecular
      dynamics simulations, reveal the details of the transformation from solid metal
      nanoparticles to hollow metal oxide nanoshells via a nanoscale Kirkendall process
      for example, coalescence of voids as they grow and reversal of mass diffusion
      direction depending on crystallinity. Our results highlight the complex interplay
      between defect chemistry and defect dynamics in determining nanoparticle
      transformation and formation.

PMID- 28428423
TI  - Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat.
AB  - The African naked mole-rat's (Heterocephalus glaber) social and subterranean
      lifestyle generates a hypoxic niche. Under experimental conditions, naked mole
      rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen
      deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat
      switches to anaerobic metabolism fueled by fructose, which is actively
      accumulated and metabolized to lactate in the brain. Global expression of the
      GLUT5 fructose transporter and high levels of ketohexokinase were identified as
      molecular signatures of fructose metabolism. Fructose-driven glycolytic
      respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis
      via phosphofructokinase, supporting viability. The metabolic rewiring of
      glycolysis can circumvent the normally lethal effects of oxygen deprivation, a
      mechanism that could be harnessed to minimize hypoxic damage in human disease.

PMID- 28428424
TI  - Biased partitioning of the multidrug efflux pump AcrAB-TolC underlies long-lived
      phenotypic heterogeneity.
AB  - The molecular mechanisms underlying phenotypic variation in isogenic bacterial
      populations remain poorly understood. We report that AcrAB-TolC, the main
      multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias
      for old cell poles by a segregation mechanism that is mediated by ternary AcrAB
      TolC complex formation. Mother cells inheriting old poles are phenotypically
      distinct and display increased drug efflux activity relative to daughters.
      Consequently, we find systematic and long-lived growth differences between mother
      and daughter cells in the presence of subinhibitory drug concentrations. A simple
      model for biased partitioning predicts a population structure of long-lived and
      highly heterogeneous phenotypes. This straightforward mechanism of generating
      sustained growth rate differences at subinhibitory antibiotic concentrations has
      implications for understanding the emergence of multidrug resistance in bacteria.

PMID- 28428425
TI  - Neonatal acquisition of Clostridia species protects against colonization by
      bacterial pathogens.
AB  - The high susceptibility of neonates to infections has been assumed to be due to
      immaturity of the immune system, but the mechanism remains unclear. By colonizing
      adult germ-free mice with the cecal contents of neonatal and adult mice, we show
      that the neonatal microbiota is unable to prevent colonization by two bacterial
      pathogens that cause mortality in neonates. The lack of colonization resistance
      occurred when Clostridiales were absent in the neonatal microbiota.
      Administration of Clostridiales, but not Bacteroidales, protected neonatal mice
      from pathogen infection and abrogated intestinal pathology upon pathogen
      challenge. Depletion of Clostridiales also abolished colonization resistance in
      adult mice. The neonatal bacteria enhanced the ability of protective
      Clostridiales to colonize the gut.

PMID- 28428429
TI  - The new tissue culture.

PMID- 28428426
TI  - Transgenerational transmission of environmental information in C. elegans.
AB  - The environment experienced by an animal can sometimes influence gene expression
      for one or a few subsequent generations. Here, we report the observation that a
      temperature-induced change in expression from a Caenorhabditis elegans
      heterochromatic gene array can endure for at least 14 generations. Inheritance is
      primarily in cis with the locus, occurs through both oocytes and sperm, and is
      associated with altered trimethylation of histone H3 lysine 9 (H3K9me3) before
      the onset of zygotic transcription. Expression profiling reveals that temperature
      induced expression from endogenous repressed repeats can also be inherited for
      multiple generations. Long-lasting epigenetic memory of environmental change is
      therefore possible in this animal.

PMID- 28428427
TI  - Microtubules acquire resistance from mechanical breakage through intralumenal
      acetylation.
AB  - Eukaryotic cells rely on long-lived microtubules for intracellular transport and
      as compression-bearing elements. We considered that long-lived microtubules are
      acetylated inside their lumen and that microtubule acetylation may modify
      microtubule mechanics. Here, we found that tubulin acetylation is required for
      the mechanical stabilization of long-lived microtubules in cells. Depletion of
      the tubulin acetyltransferase TAT1 led to a significant increase in the frequency
      of microtubule breakage. Nocodazole-resistant microtubules lost upon removal of
      acetylation were largely restored by either pharmacological or physical removal
      of compressive forces. In in vitro reconstitution experiments, acetylation was
      sufficient to protect microtubules from mechanical breakage. Thus, acetylation
      increases mechanical resilience to ensure the persistence of long-lived
      microtubules.

PMID- 28428430
TI  - Collagen beta (1-O) galactosyltransferase 1 (GLT25D1) is required for the
      secretion of high molecular weight adiponectin and affects lipid accumulation.
AB  - Secretion of high molecular weight (HMW) adiponectin is dependent on post
      translational modification (PTM) of conserved lysines in the collagenous domain.
      The present study aims to characterize the enzymes responsible for the PTM of
      conserved lysines which leads to HMW adiponectin secretion, and to define its
      significance in relation to obesity. Collagen beta (1-O) galactosyltransferase 1
      (GLT25D1) was knocked down in HEK cells modified for the stable expression of
      adiponectin (adiponectin expressing human embryonic kidney cells, Adipo-HEK) as
      well as in Simpson Golabi-Behmel-Syndrome (SGBS) adipocytes. Knockdown of GLT25D1
      caused a significant decrease in HMW adiponectin in Adipo-HEK cells with no
      change in total adiponectin. Knockdown in the SGBS cells caused an increase in
      lipid accumulation yet inhibited adipogenesis. Co-immunoprecipitation with
      adiponectin and mass spectrometry showed that adiponectin formed a protein
      complex with lysyl hydroxylase 3 (LH3) and GLT25D1. Transient overexpression of
      GLT25D1 showed that the intracellular retention of LH3 was dependent on GLT25D1.
      To determine whether changes in GLT25D1 were significant in obesity, mice were
      fed a standard chow or high-fat diet (HFD) for 5 weeks. GLT25D1 was significantly
      decreased in mice fed HFD which coincided with a decrease in HMW adiponectin. We
      conclude that GLT25D1 regulates HMW adiponectin secretion and lipid accumulation,
      consistent with changes in mice after high-fat feeding. These results suggest a
      novel function of GLT25D1 leading to decreased HMW adiponectin secretion in early
      obesity.

PMID- 28428431
TI  - The association between dietary zinc intake and risk of pancreatic cancer: a meta
      analysis.
AB  - Previous reports have suggested a potential association on dietary zinc intake
      with the risk of pancreatic cancer. Since the associations between different
      studies were controversial, we therefore conducted a meta-analysis to reassess
      the relationship between dietary zinc intake and pancreatic cancer risk. A
      comprehensive search from the databases of PubMed, Embase, Web of Science, and
      Medline was performed until January 31, 2017. Relative risk (RR) with 95%
      confidence intervals (CI) derived by using random effect model was used.
      Sensitivity analysis and publication bias were conducted. Our meta-analysis was
      based on seven studies involving 1659 cases, including two prospective cohort
      studies and five case-control studies. The total RR of pancreatic cancer risk for
      the highest versus the lowest categories of dietary zinc intake was 0.798 (0.621
      0.984), with its significant heterogeneity among studies (I2=58.2%, P=0.026). The
      average Newcastle-Ottawa scale (NOS) score was 7.29, suggesting a high quality.
      There was no publication bias in the meta-analysis about dietary zinc intake on
      the risk of pancreatic cancer. Subgroup analyses showed that dietary zinc intake
      could reduce the risk of pancreatic cancer in case-control studies and among
      American populations. In conclusion, we found that highest category of dietary
      zinc intake can significantly reduce the risk of pancreatic cancer, especially
      among American populations.

PMID- 28428433
TI  - Widespread eruption in a patient with atopic dermatitis.

PMID- 28428434
TI  - Post-operative shortness of breath.

PMID- 28428435
TI  - BET 1: A glass half full? Thrombolysis for the treatment of submassive pulmonary
      embolism.
AB  - A short-cut review was carried out to establish whether thrombolysis in addition
      to therapeutic anticoagulation could be of benefit in submassive (intermediate
      risk) pulmonary embolism (PE). 64 directly relevant papers were found using the
      reported search strategy. Of these, three presented the best evidence to answer
      the clinical question. The author, date and country of publication, patient group
      studied, study type, relevant outcomes, results and study weaknesses of these
      best papers are tabulated. It is concluded that there is insufficient evidence to
      support the routine use of adjuvant thrombolytic therapy at any dose for patients
      with submassive PE. Carefully selected patients with a low bleeding risk who
      attribute high importance to functional outcome may stand to benefit.

PMID- 28428437
TI  - BET 2: Striking the right balance: anticoagulation and isolated distal deep vein
      thrombosis.
AB  - A short-cut review was carried out to establish whether treatment of isolated
      distal deep vein thrombosis with therapeutic anticoagulation can reduce adverse
      clinical outcomes. A meta-analysis from 2011 and 11 subsequent directly relevant
      papers were found using the reported search strategy. Of these, 7 in total
      presented the best evidence to answer the clinical question. The author, date and
      country of publication, patient group studied, study type, relevant outcomes,
      results and study weaknesses of these best papers are tabulated. It is concluded
      that patients diagnosed with isolated distal deep vein thrombosis should be
      individually risk assessed and treated according to their risk of thrombotic
      complication, bleeding with anticoagulation and personal preference.

PMID- 28428438
TI  - Global emergency medicine highlights.

PMID- 28428439
TI  - A young woman with fever and low back pain.

PMID- 28428440
TI  - "I've got a lump in my throat".

PMID- 28428441
TI  - Selective Glucocorticoid Receptor Modulators (SGRMs) Delay Castrate-Resistant
      Prostate Cancer Growth.
AB  - Increased glucocorticoid receptor (GR) expression and activity following androgen
      blockade can contribute to castration-resistant prostate cancer (CRPC)
      progression. Therefore, we hypothesized that GR antagonism will have therapeutic
      benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist,
      mifepristone, lacks GR specificity, reducing its therapeutic potential. Here, we
      report that two novel nonsteroidal and highly selective GR modulators (SGRM),
      CORT118335 and CORT108297, have the ability to block GR activity in prostate
      cancer and slow CRPC progression. In contrast to mifepristone, these novel SGRMs
      did not affect androgen receptor (AR) signaling, but potently inhibited GR
      transcriptional activity. Importantly, SGRMs decreased GR-mediated tumor cell
      viability following AR blockade. In vivo, SGRMs significantly inhibited CRPC
      progression in high GR-expressing, but not in low GR-expressing xenograft models.
      Transcriptome analysis following AR blockade and GR activation revealed that
      these SGRMs block GR-mediated proliferative gene expression pathways.
      Furthermore, GR-regulated proliferation-associated genes AKAP12, FKBP5, SGK1,
      CEBPD, and ZBTB16 are inhibited by CORT108297 treatment in vivo Together, these
      data suggest that GR-selective nonsteroidal SGRMs potently inhibit GR activity
      and prostate cancer growth despite AR pathway inhibition, demonstrating the
      therapeutic potential of SGRMs in GR-expressing CRPC. Mol Cancer Ther; 16(8);
      1680-92. (c)2017 AACR.

PMID- 28428442
TI  - Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and
      Follicular Lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are the most
      prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton
      tyrosine kinase (BTK)-mediated B-cell receptor signaling pathway contributes to
      pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some
      efficacy in both indications. To improve ibrutinib efficacy through combination
      therapy, we first investigated differential gene expression in parental and
      ibrutinib-resistant cell lines to better understand the mechanisms of resistance.
      Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased
      sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from
      ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2
      gene expression. We further demonstrated synergistic growth suppression by
      ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and follicular lymphoma
      cell lines. The combination of both drugs also reduced colony formation,
      increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A
      synergistic combination effect was also found in ibrutinib-resistant cells
      generated by either genetic mutation or drug treatment. Together, these findings
      suggest a potential clinical benefit from ibrutinib and ABT-199 combination
      therapy. Mol Cancer Ther; 16(7); 1246-56. (c)2017 AACR.

PMID- 28428443
TI  - Mechanisms of Pinometostat (EPZ-5676) Treatment-Emergent Resistance in MLL
      Rearranged Leukemia.
AB  - DOT1L is a protein methyltransferase involved in the development and maintenance
      of MLL-rearranged (MLL-r) leukemia through its ectopic methylation of histones
      associated with well-characterized leukemic genes. Pinometostat (EPZ-5676), a
      selective inhibitor of DOT1L, is in clinical development in relapsed/refractory
      acute leukemia patients harboring rearrangements of the MLL gene. The observation
      of responses and subsequent relapses in the adult trial treating MLL-r patients
      motivated preclinical investigations into potential mechanisms of pinometostat
      treatment-emergent resistance (TER) in cell lines confirmed to have MLL-r. TER
      was achieved in five MLL-r cell lines, KOPN-8, MOLM-13, MV4-11, NOMO-1, and SEM.
      Two of the cell lines, KOPN-8 and NOMO-1, were thoroughly characterized to
      understand the mechanisms involved in pinometostat resistance. Unlike many other
      targeted therapies, resistance does not appear to be achieved through drug
      induced selection of mutations of the target itself. Instead, we identified both
      drug efflux transporter dependent and independent mechanisms of resistance to
      pinometostat. In KOPN-8 TER cells, increased expression of the drug efflux
      transporter ABCB1 (P-glycoprotein, MDR1) was the primary mechanism of drug
      resistance. In contrast, resistance in NOMO-1 cells occurs through a mechanism
      other than upregulation of a specific efflux pump. RNA-seq analysis performed on
      both parental and resistant KOPN-8 and NOMO-1 cell lines supported two unique
      candidate pathway mechanisms that may explain the pinometostat resistance
      observed in these cell lines. These results are the first demonstration of TER
      models of the DOT1L inhibitor pinometostat and may provide useful tools for
      investigating clinical resistance. Mol Cancer Ther; 16(8); 1669-79. (c)2017 AACR.

PMID- 28428444
TI  - Impact of atrial fibrillation on the clinical course of apical hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) is considered a 'benign'
      form of hypertrophic cardiomyopathy, with limited data on the long-term outcome.
      However, the clinical impact of atrial fibrillation (AF) in ApHCM is largely
      unknown. The hypothesis was that AF is common and has a prognostic implication in
      ApHCM. METHODS: The occurrence of AF and outcome was assessed in 306 consecutive
      patients with ApHCM (68% male, 62+/-11 years). RESULTS: AF occurred in 77
      patients with ApHCM (prevalence, 25.2%; annual incidence, 4.6%/year) and was
      independently predicted by old age and large left atrium (>45 mm). Among 70 AF
      patients indicated with anticoagulation, 53 patients (76%) received warfarin.
      During a follow-up of 5.5+/-2.0 years, the patients with AF had a higher
      incidence of all-cause death, cardiovascular death and strokes (11.7% vs 1.3%,
      6.5% vs 0.9% and 19.5% vs 2.6%, respectively, all p<0.05) than those without AF.
      When adjusted by the age and gender, those with AF still had an increased risk
      for all-cause death (HR 6.58; 95% CI 1.65-26.16, p=0.007) and strokes (HR 5.13;
      95% CI 1.85 to 14.18, p=0.002). AF was detected before the time of stroke in 8
      (53%) out of 15 patients with both AF and stroke. In addition, six out of eight
      patients were on anticoagulation at the time of stroke. The cause of death was a
      stroke in three (33%) out of nine patients with AF. CONCLUSION: In patients with
      ApHCM, AF was common and was associated with a substantial risk for strokes and
      mortality suggesting that AF should be carefully managed in ApHCM.

PMID- 28428445
TI  - Pectinase-treated Panax ginseng protects heat stress-induced testicular damage in
      rats.
AB  - Testicular hyperthermia is well studied to cause impaired spermatogenesis. In the
      present study, the protective effect of enzymatically modified (pectinase
      treated) Panax ginseng (GINST) against intermittent sub-chronic heat stress
      induced testicular damage in rats was investigated. Male Sprague-Dawley rats were
      divided into four groups: normal control (NC), heat-stressed control (HC), heat
      stressed plus GINST-100 mg/kg/day (HG100) and heat-stressed plus GINST-200
      mg/kg/day (HG200) treatment groups. GINST (100 and 200 mg/kg/day) was mixed
      separately with a regular pellet diet and was administered orally for 8 weeks
      starting from 1 week before heat exposure. Parameters such as organ weight, blood
      chemistry, sperm kinetic values, expression of antioxidant enzymes,
      spermatogenesis molecules and sex hormone receptors levels were measured. Data
      revealed that kidney and epididymis weight were significantly (P < 0.05)
      decreased with heat stress and recovered by GINST treatment. Further, the altered
      levels of blood chemistry panels and sperm kinetic values in heat stress-induced
      rats were attenuated when GINST was administered (P < 0.05). Furthermore, the
      expression levels of antioxidant-related enzymes (GSTM5 and GPX4),
      spermatogenesis-related proteins (CREB1 and INHA) and sex hormone receptors
      (androgen receptor, luteinizing hormone receptor and follicle-stimulating hormone
      receptor) were reduced by heat stress; however, GINST treatment effectively
      ameliorated these changes. In conclusion, GINST was effective in reducing heat
      induced damage in various male fertility factors in vivo and has considerable
      potential to be developed as a useful supplement in improving male fertility.

PMID- 28428446
TI  - The finite state projection approach to analyze dynamics of heterogeneous
      populations.
AB  - Population modeling aims to capture and predict the dynamics of cell populations
      in constant or fluctuating environments. At the elementary level, population
      growth proceeds through sequential divisions of individual cells. Due to
      stochastic effects, populations of cells are inherently heterogeneous in
      phenotype, and some phenotypic variables have an effect on division or survival
      rates, as can be seen in partial drug resistance. Therefore, when modeling
      population dynamics where the control of growth and division is phenotype
      dependent, the corresponding model must take account of the underlying cellular
      heterogeneity. The finite state projection (FSP) approach has often been used to
      analyze the statistics of independent cells. Here, we extend the FSP analysis to
      explore the coupling of cell dynamics and biomolecule dynamics within a
      population. This extension allows a general framework with which to model the
      state occupations of a heterogeneous, isogenic population of dividing and
      expiring cells. The method is demonstrated with a simple model of cell-cycle
      progression, which we use to explore possible dynamics of drug resistance
      phenotypes in dividing cells. We use this method to show how stochastic single
      cell behaviors affect population level efficacy of drug treatments, and we
      illustrate how slight modifications to treatment regimens may have dramatic
      effects on drug efficacy.

PMID- 28428447
TI  - Comparison of Mid-Term Graft Patency between On-Pump and Off-Pump Coronary Artery
      Bypass Grafting.
AB  - BACKGROUND: Multiple studies have compared on-pump coronary artery bypass (ONCAB)
      grafting with off-pump coronary artery bypass (OPCAB) grafting, but the optimal
      surgical strategy has yet to be established. Furthermore, there is limited
      evidence regarding mid-term graft patency rates. METHODS: Between April 2001 and
      March 2014, 365 consecutive patients underwent isolated coronary artery bypass
      grafting (CABG; male: 75%; mean age: 69 +/- 10 years). After propensity-score
      matched analysis, we assessed the results of 67 patients in each group (ONCAB:
      group A, OPCAB: group B). The mean follow-up period of graft patency and survival
      rate was 35 +/- 37 months and 54 +/- 47 months, respectively. RESULTS: There were
      no significant differences in baseline characteristics between the two groups.
      There was a trend for an increased number of distal anastomoses in group B as
      compared to group A (group A vs. group B: 3.8 +/- 1.1 vs. 4.1 +/- 1.6, P = 0.17).
      The total graft patency rate was tend to be lower in group A, but not
      statistically significant (group A: 156 months, 45.2%; group B: 96 months, 72.6%;
      P = 0.21). There was no difference for survival and major-adverse-cardiac-and
      cerebrovascular-events (MACCE) free rate (P = 0.42 and 0.76, respectively).
      CONCLUSION: Propensity-score-matched analysis revealed no difference in mid-term
      survival rate, MACCE free rate, graft patency rates, and number of distal
      anastomoses between ONCAB and OPCAB groups.

PMID- 28428448
TI  - Unruptured Cerebral Aneurysms in Elderly Patients.
AB  - The prevalence of unruptured cerebral aneurysms (UCAs) in elderly patients is
      increasing in our aging population. UCA management in elderly patients has some
      difficulties, such as reduced life expectancy, increased comorbidities and
      treatment risks, and poor prognosis in case of rupture. In this review article,
      we summarize the most recent findings on the natural history, therapeutic options
      and treatment results for UCAs exclusively in elderly patients, and describe
      possible medical treatments for patients with UCAs.

PMID- 28428449
TI  - Current Status and Outcomes of Direct Oral Anticoagulant Use in Real-World Atrial
      Fibrillation Patients - Fushimi AF Registry.
AB  - BACKGROUND: The current status and outcomes of direct oral anticoagulant (DOAC)
      use have not been widely evaluated in unselected patients with atrial
      fibrillation (AF) in the real world.Methods and Results:The Fushimi AF Registry
      is a community-based prospective survey of AF patients who visited the
      participating medical institutions (n=80) in Fushimi, Kyoto, Japan. Follow-up
      data with oral anticoagulant (OAC) status were available for 3,731 patients by
      the end of November 2015. We evaluated OAC status and clinical outcomes according
      to OAC status. The number (incidence rate) of stroke/systemic embolism (SE) and
      major bleeding events during the median follow-up of 3.0 years was 224
      (2.3%/year) and 177 (1.8%/year), respectively. After the release of DOAC, the
      prevalence of DOAC use increased gradually and steadily, and that of warfarin,
      DOAC and no OAC was 37%, 26% and 36%, respectively in 2015. On Cox proportional
      hazards modeling incorporating change in OAC status as a time-dependent covariate
      for stroke/SE and major bleeding events, use of DOAC compared with warfarin was
      not associated with stroke/SE events (HR, 0.95; 95% CI: 0.59-1.51, P=0.82) or
      major bleeding events (HR, 0.82; 95% CI: 0.50-1.36, P=0.45). CONCLUSIONS: In real
      world clinical practice, there were no significant differences in stroke/SE
      events or major bleeding events for DOAC compared with warfarin in patients with
      AF.

PMID- 28428452
TI  - MRI of Perfusion: Principles and Clinical Applications.
AB  - The principle and clinical application of measurement of cerebral blood perfusion
      (CBP) using MRI are described. Purposes of measuring CBP using MRI are wide
      ranging. Generally, it is used to diagnose cerebro-vascular disorders or brain
      tumors. There are two types of measuring methods. One is dynamic susceptibility
      contrast (DSC) method using a contrast agent as a tracer. Another is an arterial
      spin labeling (ASL) method using protons in arterial blood as an endogenous
      tracer, instead of bio-exogenous tracer. Basic theory of ASL method was published
      in the 1990s, recently, its clinical application has been spreading rapidly by
      the technological innovations. ASL method is attractive as a way to measure CBP
      because of its non-invasiveness (no radiation-exposure, not need intravenous
      injection or blood sampling), and the imaging time is about 5 minutes, thereby
      the measurement can be repeated. The analysis of DSC method has not been
      standardized, though various valuable parameters are provided. And the
      prerequisite of DSC method is uncertain in vivo. On the other hand, the result of
      ASL is affected by the post labeling delay, and limited to the arterial
      information.

PMID- 28428450
TI  - Independent and Combined Effects of Serum Albumin and C-Reactive Protein on Long
      Term Outcomes of Patients Undergoing Percutaneous Coronary Intervention.
AB  - BACKGROUND: Both inflammation and malnutrition have been reported to be closely
      linked to atherosclerosis, especially in patients with chronic kidney disease
      (CKD). The combined effects of serum albumin and C-reactive protein (CRP) on
      clinical outcomes after percutaneous coronary intervention (PCI) were
      investigated.Methods and Results:A total of 2,164 all-comer patients with
      coronary artery disease who underwent their first PCI and had data available for
      preprocedural serum albumin and hs-CRP levels between 2000 and 2011 were studied.
      Patients were assigned to 4 groups according to their median serum albumin and
      CRP levels (4.1 g/dL and 0.10 mg/dL, respectively). The incidence of major
      adverse cardiac events (MACE), including all-cause death and non-fatal myocardial
      infarction (MI), was evaluated. During a median follow-up period of 7.5 years,
      331 cases of MACE (15.3%), including 270 deaths and 61 non-fatal MIs, occurred.
      Kaplan-Meier curves showed that the rates of MACE differed significantly among
      the groups (log-rank P<0.0001), even stratified by with or without CKD (both log
      rank P<0.0001). After adjustment for established cardiovascular risk factors, low
      serum albumin with high CRP levels was associated with adverse cardiac events
      (hazard ratio 2.55, 95% confidence interval 1.72-3,88, P<0.0001, high albumin/low
      CRP group as reference). CONCLUSIONS: The presence of both low serum albumin and
      high CRP levels conferred a synergistic adverse effect on the risk for long-term
      MACE in patients undergoing PCI.

PMID- 28428451
TI  - The Relation between Serum Endostatin Level and Carotid Atherosclerosis in
      Healthy Residents of Japan: Results from the Kyushu and Okinawa Population Study
      (KOPS).
AB  - AIM: To examine the association between the serum endostatin levels and
      subclinical atherosclerosis independent of traditional risk factors in a healthy
      Japanese population. METHODS: Among 1,057 residents who attended free public
      physical examinations between 2010 and 2011, we evaluated the data of 648 healthy
      residents for whom the serum endostatin level and common carotid intima-media
      thickness (IMT) were successfully measured. RESULTS: The median endostatin level
      was 63.7 ng/mL (interquartile ranges: 49.7-93.2 ng/mL), and the mean carotid IMT
      was 0.68+/-0.12 mm. Residents with above median endostatin had significantly
      higher carotid IMT than did those with below median endostatin (0.71+/-0.14 vs.
      0.65+/-0.09 mm, P<0.001). Multiple linear regression analysis demonstrated that
      increased serum endostatin is significantly associated with carotid IMT (above
      vs. below median endostatin level; beta=0.11, P=0.03), independent of the known
      covariates of age, sex, body mass index, drinking and smoking status, systolic
      blood pressure, diastolic blood pressure, hemoglobin A1c, low density lipoprotein
      cholesterol, estimated glomerular filtration rate, and log-transformed high
      sensitive C-reactive protein. CONCLUSIONS: A higher serum endostatin level
      reflected subclinical atherosclerosis in this Japanese population.

PMID- 28428453
TI  - Quiet Technology of MRI.
AB  - A number of clinical applications for MRI have been developed in accordance with
      the advancement in imaging technology. Recently, medical checkup of brain or
      heart are becoming popular. In this situation, there is a growing need for
      performance improvement of MRI and thus acoustic noise during examinations tends
      to become louder with the use of higher static magnetic field and higher gradient
      performance. Noise reduction measures for MRI are classified into two categories,
      pulse sequence optimization and hardware renovation. For pulse sequence, noise is
      reduced by decreasing the changes of the current applied for gradient coil. Since
      there exist solid-borne sound and airborne sound, for hardware measure, not only
      making gradient coil itself vibration suppressed structure but also controlling
      vibration to prevent propagation of sounds to the other structure is required.
      PianissimoTM mechanism employs both solid-borne sound suppression and airborne
      sound suppression by vacuum-encapsulating the gradient coil, and realizes 33 dB
      noise reduction. PianissimoTM mechanism, in contrast to the noise reduction by
      pulse sequence modification, reduces the acoustic noise produced by scans of all
      kinds and can be readily adapted to the newly developed applications regardless
      of imaging technique.

PMID- 28428454
TI  - Series: Practical Evaluation of Clinical Image Quality (3): Subjective Evaluation
      of Image Quality in Digital Radiography Systems.
AB  - In the environment of picture archiving and communication system (PACS), the
      subjective evaluation of medical image quality is performed using an image
      display monitor. Commonly, PACS and its image viewer can handle digital imaging
      and communications in medicine (DICOM) format image files that are displayed as 8
      bit grayscale images in the monitor. However, the original grayscale of DICOM
      image is between 10-bit to 16-bit depth. Therefore, in order for DICOM images to
      be displayed in the monitor by PACS image viewer, they need to be converted into
      8-bit depth grayscale. This conversion indicates that the original
      characteristics of DICOM images are altered when they are displayed in the
      monitor by PACS image viewer. Moreover, image data interpolation to match the
      image matrix for the resolution of the monitor also alters the characteristics of
      images. For these reasons, it is a must to recognize the influential factors of
      image display settings for the subjective evaluation of medical image quality.

PMID- 28428455
TI  - Diagnostic Reference Levels: DRLs.

PMID- 28428456
TI  - Inaugural Message from the President of the Japan Society of Medical Physics.

PMID- 28428457
TI  - Preface to the Special Issue: MRI in Medical Physics.

PMID- 28428458
TI  - A Proposal for the Absorbed Dose to Water Dosimetry for Flattening Filter-free
      Beams.
AB  - Flattening filter-free (FFF) beams generated by linear accelerators have been
      widely adopted in many hospitals recently for radiation therapy. FFF technology
      can provide higher dose rates so that shortening of the treatment time and less
      intra-fraction motion error are expected.In Japan, the current way of determining
      absorbed dose to water for FFF beams is to follow the Standard Dosimetry 12
      protocol which was developed for flattened beams. Since it has been reported that
      the flattened beams and FFF beams have different beam properties, it is necessary
      to evaluate the usefulness of Standard Dosimetry 12 protocol for FFF beam
      dosimetry.This report reviews physical and dosimetric properties of FFF beams
      especially in terms of the effect on absorbed dose to water dosimetry using an
      ionization chamber. From the review, it became evident that the absorbed dose to
      water is underestimated by volume averaging effect of the ionization chamber. On
      the other hand, the absorbed dose to water is overestimated by using the beam
      quality specifier TPR20,10 to predict the restricted mass collision stopping
      power ratio for FFF beams. Therefore, an alternative method was proposed for
      absorbed dose to water dosimetry of FFF beams based on Standard Dosimetry 12.

PMID- 28428459
TI  - Essentials of Brain MRS: Fundamentals and Clinical Applications.
AB  - 1H-MRS (proton magnetic resonance spectroscopy) is a method for analyzing
      material components using the difference of the frequency (chemical shift) in
      magnetic resonance. 1H-MRS for human body is able to diagnose the clinical
      conditions by non-invasive analysis of materials in organs. However, the
      mechanical limitations and complexity in analyses prevented it from becoming
      popular as MRI (magnetic resonance imaging). Recently, an ideal environment for
      1H-MRS is commonly available such as stronger magnetic field and improved
      software, yet we still lack common knowledges about 1H-MRS which makes whom plans
      to start it difficult. In this article, the principle, tips, clinical
      applications and spectrum evaluations were explained focusing on novice users.

PMID- 28428460
TI  - An Encouragement of Functional MRI.

PMID- 28428461
TI  - Basic Principle and Image Analysis in the Diffusion Tensor Image.
AB  - The magnetic resonance imaging (MRI) is established as the imaging technique that
      is essential to the imaging of the central nervous system disease. Above all, the
      diffusion weighted image (DWI) is known as the tool which can diagnose acute
      ischemic stroke with high accuracy in a short time. DTI, an applied form of DWI,
      was devised as a technique to image the structure of the brain white matter. In
      clinical sites, this technique is used for pathologic elucidation such as the
      intracerebral tissue injury or mental disorder. Additionally, diffusion tensor
      tractography (DTT), which is a technique to build three-dimensional structure of
      the neural fiber tracts, is used for grasping the relations between a brain tumor
      and the fibers tract. Therefore, these techniques may be useful imaging tools in
      the central nerve region.

PMID- 28428462
TI  - Serialization about Practical Evalution of Image Quality in Medical Image.

PMID- 28428463
TI  - Accuracy Verification of Respiratory-gated Radiotherapy that Combines the
      Respiration-Monitoring Device and Respiratory-gated System.
AB  - The purpose of this study is to evaluate the mechanical accuracy of a respiratory
      gated radiation system that combines the Linear Indicator-equipped Abches
      respiration-monitoring device and the Varian Real-time Position Management system
      (LI-RPM system). This combined configuration, implemented for the first time in
      Japan, was compared with the stand-alone Varian RPM system (RPM system). The
      delay times, dose profiles, and output waveforms of the LI-RPM and RPM systems
      were evaluated using a self-produced dynamic phantom. The delay times for the LI
      RPM and RPM systems were both 0.1 s for 4 s and 8 s test periods. The
      corresponding output waveform correlation factors (R2) for the 4 s and 8 s test
      periods were 0.9981 and 0.9975, respectively. No difference was observed in the
      dose profiles of the two systems. Thus, the present results indicate that the
      proposed LI-RPM combined respiratory-gated radiation system has similar
      properties to the RPM system. However, it offers several advantages in terms of
      its versatility, including its alignment assistance capabilities for non-coplanar
      treatments.

PMID- 28428464
TI  - Notes on the Ingenuity of the Monte Carlo Code PHITS.

PMID- 28428465
TI  - Series: Utilization of Differential Equations and Methods for Solving Them in
      Medical Physics (3).
AB  - In this issue, simultaneous differential equations were introduced. These
      differential equations are often used in the field of medical physics. The
      methods for solving them were also introduced, which include Laplace transform
      and matrix methods. Some examples were also introduced, in which Laplace
      transform and matrix methods were applied to solving simultaneous differential
      equations derived from a three-compartment kinetic model for analyzing the
      glucose metabolism in tissues and Bloch equations for describing the behavior of
      the macroscopic magnetization in magnetic resonance imaging.In the next (final)
      issue, partial differential equations and various methods for solving them will
      be introduced together with some examples in medical physics.

PMID- 28428466
TI  - Series: Practical Evaluation of Clinical Image Quality (1):Image Quality
      Verification of Digital Radiography.
AB  - The way of clinical image viewing has changed dramatically by deploying picture
      archiving and communication system (PACS) in clinical practices. This change has
      been caused by the digitization of clinical diagnostic images and based on
      digital imaging and communications in medicine (DICOM) 3.0 standard published in
      1992. In the PACS environment, medical displays such as liquid crystal display
      (LCD) monitors are applying for soft-copy reading. These changes in the way of
      the clinical image viewing caused by the PACS resulted in development of a new
      concept of the clinical image quality. In digital radiography, there are various
      factors that affect the image quality in the PACS environment. In addition, image
      quality can practically be classified into 3 classes; Raw data image class,
      Processed image class, and Display image class. Therefore, we must apply
      appropriate procedure to evaluate the image quality of digital radiography.

PMID- 28428467
TI  - Effects of Mathematical Analysis of Test Injection on the CT Value Estimation of
      the Aorta.
AB  - The circulation time and the mechanical acceleration time (MA time) of an
      automatic injector were simulated using pharmacokinetic analysis. The addition
      method and transfer-function method, which are mathematical techniques used for
      analyzing the test bolus method in multi-detector computed tomography, were used
      to verify the accuracy of estimation of the time-enhancement curve (TEC) of the
      main bolus. The TEC estimated using the addition method, and the TEC of the main
      bolus matched completely only if the MA time of the automatic injector was set to
      0 seconds. Moreover, the estimation accuracy of the TEC deteriorated when the MA
      time was set according to the TEC estimated by the addition method. In contrast,
      the TEC estimated using the transfer-function method, except when the MA time of
      the automatic injector was 0 seconds, had higher accuracy than the TEC estimated
      using the addition method. In this study, the addition method, a number of
      additions of TEC, and MA time of the automatic injector were found to have a
      negative effect on the estimation accuracy of the main bolus. The use of the
      transfer-function method for determining the TEC and the MA time has a positive
      effect on the estimation accuracy of the main bolus.

PMID- 28428468
TI  - Multicenter Investigation of the Effective Dose for Whole-body CT Scanning.
AB  - OBJECTIVE: To study whether the actual radiation exposure is different between
      computed tomography (CT) scanners and medical centers when the same patient is
      scanned, we investigated the actual effective doses for a whole body (Chest
      Pelvis) CT scan in a multicenter study. MATERIALS AND METHODS: Data from subjects
      were collected using 12 CT scanners at six medical centers in Yamagata city.
      Effective-dose data were acquired by scanning the same phantom (ATOM Dosimetry
      Phantoms Model702-B) using 120 kV tube voltage. Effective doses were calculated
      using corrected data from a radiophotoluminescent glass dosimeter (GD-302M). GD
      302M had energy- dependent issues, which needed to be corrected. Also,
      differences in sensitivity based on arrangement within the phantom were
      insignificant. RESULTS: The mean effective energy was 48.6 keV (range, 42.5-55.4
      keV), and the mean effective dose was 16.3 mSv (range, 8.9-26.0 mSv). The mean
      effective dose with a hybrid type iterative reconstruction was 10.7 mSv (range,
      8.9-16.4 mSv), but the mean effective dose without any iterative reconstruction
      was 20.3 mSv (range, 16.2-26.0 mSv). We found an approximate linear correlation
      between dose length product (DLP) on operation consoles and the effective dose.
      CONCLUSION: We suggest that the actual radiation exposure was different at each
      medical center when the same patient is scanned.

PMID- 28428469
TI  - Verification of the Injection Pressure Reduction Effect Using the Novel
      Indwelling Needle for Contrast-enhanced CT.
AB  - PURPOSE: The purpose of this study was to investigate the injection pressure
      reduction effect of the novel indwelling needle (Becton, Dickinson and Company).
      METHOD: We evaluated the period of 651 patients who underwent dynamic computed
      tomography. We compared the maximum injection pressure. The contrast medium was
      administered at 320, 350, and 370 mgI/ml. RESULT: The maximum injection pressure
      of the novel indwelling needle in 22 G was decreased 10% compared with SC5 in all
      contrast media. The maximum injection pressure of BDN in 20 G decreases 8%
      compared with SC5 at 370 mgI/ml, but there was no reduction at 320 mgI/ml and 350
      mgI/ml. CONCLUSION: Our analysis demonstrated that BDN significantly reduced the
      injection pressure especially in 22 G and using high concentration contrast
      medium in 20 G.

PMID- 28428470
TI  - Effects of Valsalva Maneuver by Different Breath-holding Techniques to Detect
      Pulmonary Thromboembolism in a Contrast-enhanced Computed Tomography Examination.
AB  - The purpose of this study is to measure the hemodynamics on the effect of
      Valsalva maneuver aiming at pulmonary thromboembolism (PTE) using 2-dimensional
      (2D) phase contrast imaging of magnetic resonance image (MRI), Philips Ingenia
      3.0-tesla (T). The maximal inspiration reduced the blood flow rate in various
      degrees at all measurement positions, superior vena cava (SVC), inferior vena
      cava (IVC), pulmonary artery (PA), ascending aorta (AA), and descending aorta
      (DA). This result suggests that the contrast effect in the PA might become weak
      during general PA phase to give a substantial influence of Valsalva maneuver in
      the condition after maximum inspiration. A contrast-enhanced computed tomography
      (CT) examination aiming at detection for PTE should be scanned without an advance
      maximum inspiration.

PMID- 28428471
TI  - Motion-frozen Imaging by Gated Myocardial Perfusion Single Photon Emission
      Computed Tomography Using Multi-focus Fan Beam Collimator in Thallium-201 Study.
AB  - PURPOSE: This study aimed to evaluate the statistical noise of motion-frozen (MF)
      image generated by gated myocardial perfusion single photon emission computed
      tomography (SPECT) imaging using IQ . SPECT and to determine the optimal
      acquisition and reconstruction parameters for MF image using IQ . SPECT. METHODS:
      A movement cardiac phantom and static cardiac phantom were used to acquire the MF
      images. The acquisition times used were different in 8 and 16 frames per R-R
      interval, and varying reconstruction parameters (subset and iteration) were used.
      We determined the %CV value, contrast, and normalized mean square error (NMSE) to
      evaluate the image quality. RESULTS: The %CV value for a MF image with IQ . SPECT
      was lower than that for a conventional non-gated myocardial perfusion SPECT (MPS)
      image with low energy high resolution (LEHR). With regard to the acquisition
      parameters, the contrast did not change when the acquisition time was increased
      in 8 and 16 frames per R-R interval. NMSE converged in 56 beats/view in 8 frames
      per R-R interval. With regard to the reconstruction parameters, the contrast and
      the %CV value of the anterior and septal wall converged in update 40. The minimum
      NMSE in subsets 1, 2, and 3 were almost similar. CONCLUSIONS: Uniformity in the
      MF image with IQ . SPECT was higher than that in the conventional image. The
      results of this MF image with IQ . SPECT study suggest that the optimal
      acquisition parameter should be 56 beats/view in 8 frames per R-R interval, and
      the optimal reconstruction parameters should be subset 3 and iteration 14.

PMID- 28428472
TI  - Examination of a Method to Determine the Reference Region for Calculating the
      Specific Binding Ratio in Dopamine Transporter Imaging.
AB  - The specific binding ratio (SBR) was first reported by Tossici-Bolt et al. for
      quantitative indicators for dopamine transporter (DAT) imaging. It is defined as
      the ratio of the specific binding concentration of the striatum to the non
      specific binding concentration of the whole brain other than the striatum. The
      non-specific binding concentration is calculated based on the region of interest
      (ROI), which is set 20 mm inside the outer contour, defined by a threshold
      technique. Tossici-Bolt et al. used a 50% threshold, but sometimes we couldn't
      define the ROI of non-specific binding concentration (reference region) and
      calculate SBR appropriately with a 50% threshold. Therefore, we sought a new
      method for determining the reference region when calculating SBR. We used data
      from 20 patients who had undergone DAT imaging in our hospital, to calculate the
      non-specific binding concentration by the following methods, the threshold to
      define a reference region was fixed at some specific values (the fixing method)
      and reference region was visually optimized by an examiner at every examination
      (the visual optimization method). First, we assessed the reference region of each
      method visually, and afterward, we quantitatively compared SBR calculated based
      on each method. In the visual assessment, the scores of the fixing method at 30%
      and visual optimization method were higher than the scores of the fixing method
      at other values, with or without scatter correction. In the quantitative
      assessment, the SBR obtained by visual optimization of the reference region,
      based on consensus of three radiological technologists, was used as a baseline
      (the standard method). The values of SBR showed good agreement between the
      standard method and both the fixing method at 30% and the visual optimization
      method, with or without scatter correction. Therefore, the fixing method at 30%
      and the visual optimization method were equally suitable for determining the
      reference region.

PMID- 28428473
TI  - Technical Considerations on Scanning and Image Analysis for Amyloid PET in
      Dementia.
AB  - Brain imaging techniques, such as computed tomography (CT), magnetic resonance
      imaging (MRI), single photon emission computed tomography (SPECT), and positron
      emission tomography (PET), can provide essential and objective information for
      the early and differential diagnosis of dementia. Amyloid PET is especially
      useful to evaluate the amyloid-beta pathological process as a biomarker of
      Alzheimer's disease. This article reviews critical points about technical
      considerations on the scanning and image analysis methods for amyloid PET. Each
      amyloid PET agent has its own proper administration instructions and recommended
      uptake time, scan duration, and the method of image display and interpretation.
      In addition, we have introduced general scanning information, including subject
      positioning, reconstruction parameters, and quantitative and statistical image
      analysis. We believe that this article could make amyloid PET a more reliable
      tool in clinical study and practice.

PMID- 28428474
TI  - Evaluation of Absorbed Dose for CBCT in Image-guided Radiation Therapy:
      Comparison of Each Devices and Facilities.
AB  - Recently, intensity-modulated radiation therapy (IMRT) is used worldwide, highly
      accurate verification of the location using image-guided radiation therapy (IGRT)
      has become critical. However, the use of cone-beam computed tomography (CBCT) to
      ascertain the location each time raises concerns about its influence on
      radiotherapy dosage and increased radiation exposure. The purpose of this study
      was to measure the absorbed dose using nine kilovoltage (kV) devices and two
      megavoltage (MV) devices (total 11 devices) at eight facilities, compare the
      absorbed dose among the devices, and assess the characteristics of the respective
      devices to ensure optimal clinical operation. For the measurement of the absorbed
      dose, a farmer-type ionization chamber dosimeter, calibrated using a 60Co and an
      IMRT dose verification phantom manufactured from water-equivalent material RW3,
      was used to measure the absorbed dose at nine points in the phantom for two
      regions, the pelvic and cephalic region. The average absorbed dose of the pelvic
      region was 3.09+/-0.21 cGy in kV-CBCT (OBI), 1.16+/-0.16 cGy in kV-CBCT (XVI),
      5.64+/-1.48 cGy in MV-CBCT (4 MV), and 6.33+/-1.54 cGy in MV-CBCT (6 MV). The
      average absorbed dose of the cephalic region was 0.38+/-0.03 cGy in kV-CBCT
      (OBI), 0.23+/-0.06 cGy in kV-CBCT (XVI), 4.02+/-0.72 cGy in MV-CBCT (4 MV), and
      4.46+/-0.77 cGy in MV-CBCT (6 MV). There was a difference in the absorbed dose at
      the measured points as well as in the dose distribution in the phantom cross
      section. No major difference was observed in the absorbed dose among identical
      devices, but a difference was identified among the devices installed at multiple
      facilities. Therefore, the angle of rotation should be paid attention to when
      CBCT is taken, and the image-taking conditions should be determined. In addition,
      it is important to handle the devices only after ascertaining the absorbed dose
      of each device.

PMID- 28428475
TI  - 10. Surgical Treatment of Hepatocellular Carcinoma.

PMID- 28428476
TI  - Preface.

PMID- 28428477
TI  - 1. Making a Diagnosis of Prostatic Disorders Based on the Recent Imaging
      Procedures.

PMID- 28428478
TI  - The Trend of the IEC & JIS Standards for the Safety of Medical Electrical
      Equipment.

PMID- 28428479
TI  - Role of Articles Written in Japanese or English in Academic Journals.

PMID- 28428480
TI  - Exposure to High Glucose Concentration Decreases Cell Surface ABCA1 and HDL
      Biogenesis in Hepatocytes.
AB  - AIM: To study atherosclerosis risk in diabetes, we investigated ATP-binding
      cassette transporter A1 (ABCA1) expression and high-density lipoprotein (HDL)
      biogenesis in the liver and hepatocytes under hyperglycemic conditions. METHODS
      AND RESULTS: In streptozotocin-induced diabetic mice, plasma HDL decreased while
      ABCA1 protein increased without changing its mRNA in the liver, only in the
      animals that responded to the treatment to show hypoinsulinemia and fasting
      hyperglycemia but not in the poor responders not showing those. To study the
      mechanism for this finding, hepatocytes were isolated from the control and
      diabetic mice, and they showed no difference in expression of ABCA1 protein, its
      mRNA, and HDL biogenesis in 1 g/l d-glucose but showed decreased HDL biogenesis
      in 4.5 g/l d-glucose although ABCA1 protein increased without change in its mRNA.
      Similar findings were confirmed in HepG2 cells with d-glucose but not with l
      glucose. Thus, these cell models reproduced the in vivo findings in
      hyperglycemia. Labeling of cell surface protein revealed that surface ABCA1
      decreased in high concentration of d-glucose in HepG2 cells despite the increase
      of cellular ABCA1 while not with l-glucose. Immunostaining of ABCA1 in HepG2
      cells demonstrated the decrease of surface ABCA1 but increase of intracellular
      ABCA1 with high d-glucose. Clearance of ABCA1 was retarded both in primary
      hepatocytes and HepG2 cells exposed to high d-glucose but not to l-glucose, being
      consistent with the decrease of surface ABCA1. CONCLUSIONS: It is suggested that
      localization of ABCA1 to the cell surface is decreased in hepatocytes in
      hyperglycemic condition to cause decrease of HDL biogenesis.

PMID- 28428481
TI  - Serum Tartrate-resistant Acid Phosphatase-5b Levels are Associated with the
      Severity and Extent of Coronary Atherosclerosis in Patients with Coronary Artery
      Disease.
AB  - AIMS: Tartrate-resistant acid phosphatase (TRACP)-5b and osteoprotegerin (OPG)
      are specific and sensitive markers of bone resorption in patients with rheumatoid
      arthritis (RA) and chronic kidney disease (CKD). The TRACP-5b level is associated
      with the severity of RA and CKD, while the OPG level is associated with the
      severity of coronary atherosclerosis and calcification, and can predict a poor
      outcome in patients with coronary artery disease (CAD). However, the impact of
      TRACP-5b on coronary atherosclerosis in CAD patients remains unclear. METHODS: A
      total of 71 CAD patients (57 men, 14 women; mean age: 69.0+/-9.7 years) and 28
      age- and gender- matched healthy subjects were investigated. The number of
      diseased vessels (a marker of the severity of coronary atherosclerosis) and the
      Gensini score (a marker of the extent of coronary atherosclerosis), as well as
      the OPG and TRACP-5b levels were measured in CAD patients. The TRACP-5b levels
      were classified into quartiles. RESULTS: The TRACP-5b levels were significantly
      higher in CAD patients than in healthy subjects. Patients with higher TRACP-5b
      levels had higher OPG levels and Gensini scores than those with lower TRACP-5b
      levels. Higher TRACP-5b levels were associated with an increased number of
      diseased vessels. A multivariate linear regression analysis showed that the OPG
      level and the number of diseased vessels or the Gensini score were significantly
      and independently associated with the TRACP-5b level. CONCLUSIONS: These data
      indicate that the TRACP-5b level is significantly associated with the OPG level
      and with the severity and extent of coronary atherosclerosis in CAD patients.

PMID- 28428482
TI  - Triglyceride Rich Lipoprotein -LPL-VLDL Receptor and Lp(a)-VLDL Receptor Pathways
      for Macrophage Foam Cell Formation.
AB  - Very low-density lipoprotein (VLDL) receptor is a member of the low-density
      lipoprotein (LDL) receptor family. It binds triglyceride rich lipoprotein (TGRL)
      but not LDL, because it recognizes apolipoprotein (apo)E only but not apoB. The
      VLDL receptor functions as a peripheral lipoprotein receptor in concert with
      lipoprotein lipase (LPL) in heart, muscle, adipose tissue and macrophages. In
      contrast to the LDL receptor, VLDL receptor binds apo E2/2 VLDL and apoE3/3 VLDL
      particles, and its expression is not down-regulated by intracellular
      lipoproteins. It has been reported that both LDL-cholesterol (LDL-C) and
      postprandial triglyceride (chyromicron and VLDL remnants) are risk factors for
      human atherosclerotic cardiovascular disease (ASCVD). True ligands such as
      lipoprotein particles of the VLDL receptor are chyromicron remnant (CMR) and VLDL
      remnant (postprandial hyperlipidemia). Although the oxidized LDL (oxLDL)
      scavenger receptors pathway is considered to be the main mechanism for macrophage
      foam cell formation, it seems that the TGRL-LPL-VLDL receptor pathway is also
      involved. Since Lp(a) is one of the ligands for the VLDL receptor, the Lp(a)-VLDL
      receptor pathway is another potential alternative. The expression of VLDL
      receptor protein in mouse macrophages is modest compared to that in rabbit and
      human macrophages, both in vitro and in vivo. Therefore, we need to elucidate the
      mechanism of human ASCVD not by using the mouse model and scavenger receptors
      pathway but instead using the rabbit model and VLDL receptor pathway,
      respectively.

PMID- 28428483
TI  - A retrospective study of anesthesia for subcutaneous ureteral bypass placement in
      cats: 27 cases.
AB  - The goals of this retrospective clinical case series study were to describe the
      management of anesthesia, and to report perioperative complications in cats
      undergoing subcutaneous ureteral bypass (SUB) placement due to ureteral
      obstruction. Medical records of client-owned cats with ureteral obstruction and
      anesthetized for SUB placement between 2012 and 2015 in a veterinary teaching
      hospital were reviewed. Twenty-seven cases were identified. Duration of
      anesthesia and surgery (mean +/- standard deviation) were 215 +/- 42 min and 148
      +/- 36 min, respectively. Hypothermia was the most common intraoperative
      complication. Hypotension, hypocapnia, hypertension and bradycardia were also
      frequently observed. Out of 22 cats who experienced intraoperative hypotension,
      17 received inotropes and vasopressors. There was a significant decrease in
      creatinine (P=0.008) and total solids (P=0.007) after SUB placement when compared
      with baseline values. Postoperative complications included pain, anorexia,
      nausea, hypertension, and urinary tract-related problems. No death occurred in
      the postoperative period. Successful management of anesthesia for SUB placement
      involves rigorous anesthetic monitoring and immediate treatment of complications.
      Perioperative complications appear to be common. This study could not identify
      risk factors associated with this procedure.

PMID- 28428484
TI  - Individual identification of Eurasian otters (Lutra lutra) in South Korea
      (Sincheon River, Daegu) by microsatellite markers.
AB  - The objective of this study was to determine the number of Eurasian otters (Lutra
      lutra) that occupied the Sincheon River in Daegu, South Korea. Twenty-seven
      spraints collected from February to May 2016 at four sites (Jangam Bridge
      approximately 6.1 km from the Gachang Dam, Docheong Bridge approximately 13.5 km,
      Chimsan Bridge approximately 15.1 km and Nogoek Bridge approximately 18 km) along
      the Sincheon River (approximately 27.06 km) were analyzed using 12 microsatellite
      markers. The analyses resulted in the identification of 16 (59.3%) individual
      Eurasian otters in the Sincheon River based on the 27 spraints. Of the 16
      individual Eurasian otters, seven were male, and nine were female. Groups were
      centered at the Jangam Bridge (3 males and 2 females), Chimsan Bridge (2 males
      and 3 females) and Docheong Bridge (2 males and 4 females). Thus, the 16 Eurasian
      otters formed three genetically related groups in each sampling area. The number
      of alleles per locus varied from three to seven, with a mean value of 5.08
      alleles.

PMID- 28428485
TI  - Pathological lesions in the central nervous system and peripheral tissues of ddY
      mice with street rabies virus (1088 strain).
AB  - Most studies on rabies virus pathogenesis in animal models have employed fixed
      rabies viruses, and the results of those employing street rabies viruses have
      been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus
      (1088 strain) in mice, 106 focus forming units were inoculated into the right
      hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild
      inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the
      right lumbosacral spinal dorsal root ganglia showed chromatolysis. Axonal
      degeneration and inflammatory cells increased with infection progress in the
      spinal dorsal horn and dorsal root ganglia. Right hindlimb paralysis was observed
      from 7 DPI, which progressed to quadriparalysis. However, no pathological changes
      were observed in the ventral horn and root fibers of the spinal cord. Viral
      antigen was first detected in the right hindlimb muscle at 3 DPI, followed by the
      right lumbosacral dorsal root ganglia, dorsal horn of spinal cord, left red
      nuclei, medulla oblongata and cerebral cortex (M1 area) at 5 DPI. These results
      suggested that the 1088 virus ascended the lumbosacral spinal cord via mainly
      afferent fibers at early stage of infection and moved to cerebral cortex (M1
      area) using descending spinal tract. Additionally, we concluded that significant
      pathological changes in mice infected with 1088 strain occur in the sensory tract
      of the spinal cord; this selective susceptibility results in clinical features of
      the disease.

PMID- 28428486
TI  - Antioxidative Protection of Squalene Adjuvant and Rabies Vaccine with Adjuvant.
AB  - The authors verified the possibility of antioxidative protection of squalene
      adjuvant emulsions by the antioxidants alpha-tocopherol and beta-carotene. They
      determined the influence of beta-carotene on the stability and antigenic
      effectiveness of adjuvant emulsion in combination with rabies vaccine. The
      composition of the adjuvant emulsions or vaccines was: 2.5% squalene; 6%
      detergents; 0.5% antioxidant; 91% water phase. The oxidative injury after UV
      irradiation was followed by the detection of the peroxide value of the emulsions.
      The stability of the emulsions was evaluated by the determination of the
      emulsion's particle size. The level of rabies antibodies (RAB) in mice sera until
      day 90 after vaccination, was determined by the rapid fluorescent focus
      inhibition test. In the in vitro system of squalene adjuvant, alpha-tocopherol
      acted as a prooxidant, while beta-carotene effectively reduced the oxidative
      injury. The homogenization of the squalene adjuvant during a prolonged period
      from 8 to 10 min did not change the particle size. The oxidation processes were
      efficiently reduced by beta-carotene during the preparation process and also
      during the 70-d storage. The vaccine with beta-carotene induced a gradual
      increase in the RAB levels with the highest value on day 28. While the
      inactivated rabies vaccine with adjuvant without beta-carotene developed a rapid
      formation of RAB, the application of the vaccine with beta-carotene induced a
      slower but more uniform production of RAB. The level of RAB was significantly
      higher after the application of the vaccine with beta-carotene and reached the
      protective value of 0.5 IU/mL, in contrast to the vaccine without beta-carotene.

PMID- 28428487
TI  - Association Between Serum Vitamin D and All-Cause and Cause-Specific Death in a
      General Japanese Population - The Hisayama Study.
AB  - BACKGROUND: Few studies have investigated the association between serum vitamin D
      levels and mortality in general Asian populations.Methods and Results:We examined
      the association of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels with the
      risk of all-cause and cause-specific death in an average 9.5-year follow-up study
      of 3,292 community-dwelling Japanese subjects aged >=40 years (2002-2012). The
      multivariable-adjusted hazard ratio (HR) for all-cause death increased
      significantly with lower serum 1,25(OH)2D levels (HR 1.54 [95% confidence
      interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd
      quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest
      quartile; P for trend <0.001). A similar association was observed for
      cardiovascular and respiratory infection death (both P for trend <0.01), but not
      for cancer death or death from other causes. In the stratified analysis, the
      association between lower serum 1,25(OH)2D levels and the risk of respiratory
      infection death was stronger in subjects with an estimated glomerular filtration
      rate (eGFR) <60 mL/min/1.73 m2than in those with eGFR >=60 mL/min/1.73 m2; there
      was a significant heterogeneity in the association between eGFR levels (P for
      heterogeneity=0.04). CONCLUSIONS: The findings suggested that a lower serum
      1,25(OH)2D level is a potential risk factor for all-cause death, especially
      cardiovascular and respiratory infection death, in the general Japanese
      population, and that lower serum 1,25(OH)2D levels greatly increase the risk of
      respiratory infection death in subjects with kidney dysfunction.

PMID- 28428488
TI  - Improvement in Exercise Capacity by Exercise Training Associated With Favorable
      Clinical Outcomes in Advanced Heart Failure With High B-Type Natriuretic Peptide
      Level.
AB  - BACKGROUND: The efficacy of exercise training (ET) programs and its relationship
      with long-term clinical outcomes in advanced heart failure (HF) patients with
      high levels of B-type natriuretic peptide (BNP) remain uncertain.Methods and
      Results:We studied 340 consecutive HF patients with ejection fraction (EF) <45%
      who completed a 3-month ET program. Patients with BNP >=200 pg/mL (High-BNP,
      n=170) had more advanced HF characteristics, including lower EF (25.0+/-8.6% vs.
      28.1+/-8.0%, P=0.0008), than those with BNP <200 pg/mL. In the High-BNP patients,
      peak oxygen uptake (VO2) was significantly increased by 8.3+/-16.2% during the ET
      program, and changes in peak VO2inversely correlated with changes in BNP (R=
      0.453, P<0.0001) and changes in ventilatory efficiency (VE/VCO2slope) (R=-0.439,
      P<0.0001). During a median follow-up of 46 months, patients in the upper tertile
      of changes in peak VO2(>=13.0%), compared with those in the lower tertile
      (<1.0%), had lower rates of the composite of all-cause death or HF
      hospitalization (37.9% vs. 54.4%, P=0.036) and all-cause death (8.6% vs. 24.6%,
      P=0.056). In the multivariate analysis, change in peak VO2was a significant
      independent predictor of the composite outcome and all-cause death. CONCLUSIONS:
      Even among advanced HF patients with high BNP level, an ET program significantly
      improved exercise capacity, and a greater improvement in exercise capacity was
      associated with greater decreases in BNP level and VE/VCO2slope and more
      favorable long-term clinical outcomes.

PMID- 28428490
TI  - Machine Learning Leading the Way for Medical Physics: Preface to the Special
      Issue.

PMID- 28428489
TI  - Superior Rhythm Discrimination With the SmartShock Technology Algorithm - Results
      of the Implantable Defibrillator With Enhanced Features and Settings for
      Reduction of Inaccurate Detection (DEFENSE) Trial.
AB  - BACKGROUND: Shocks delivered by implanted anti-tachyarrhythmia devices, even when
      appropriate, lower the quality of life and survival. The new SmartShock
      Technology(r)(SST) discrimination algorithm was developed to prevent the delivery
      of inappropriate shock. This prospective, multicenter, observational study
      compared the rate of inaccurate detection of ventricular tachyarrhythmia using
      the SST vs. a conventional discrimination algorithm.Methods and
      Results:Recipients of implantable cardioverter defibrillators (ICD) or cardiac
      resynchronization therapy defibrillators (CRT-D) equipped with the SST algorithm
      were enrolled and followed up every 6 months. The tachycardia detection rate was
      set at >=150 beats/min with the SST algorithm. The primary endpoint was the time
      to first inaccurate detection of ventricular tachycardia (VT) with conventional
      vs. the SST discrimination algorithm, up to 2 years of follow-up. Between March
      2012 and September 2013, 185 patients (mean age, 64.0+/-14.9 years; men, 74%;
      secondary prevention indication, 49.5%) were enrolled at 14 Japanese medical
      centers. Inaccurate detection was observed in 32 patients (17.6%) with the
      conventional, vs. in 19 patients (10.4%) with the SST algorithm. SST
      significantly lowered the rate of inaccurate detection by dual chamber devices
      (HR, 0.50; 95% CI: 0.263-0.950; P=0.034). CONCLUSIONS: Compared with previous
      algorithms, the SST discrimination algorithm significantly lowered the rate of
      inaccurate detection of VT in recipients of dual-chamber ICD or CRT-D.

PMID- 28428491
TI  - An Introduction to Machine Learning.

PMID- 28428492
TI  - Questionnaire Survey of Japanese Medical Physicists for Working Conditions in
      2014.

PMID- 28428493
TI  - Segmentation, Classification, and High Resolution of Image by Machine Learning.

PMID- 28428494
TI  - Machine Learning for Computer-aided Diagnosis.
AB  - Machine learning algorithms are to analyze any dataset to extract data-driven
      model, prediction rule, or decision rule from the dataset. Various machine
      learning algorithms are now used to develop high-performance medical image
      processing systems such as computer-aided detection (CADe) system which detects
      clinically significant objects from medical images and computer-aided diagnosis
      (CADx) system which quantifies malignancy of manually or automatically detected
      clinical objects. In this paper, we introduce some applications of machine
      learning algorithms to the development of medical image processing system.

PMID- 28428495
TI  - Applications of Machine Learning for Radiation Therapy.
AB  - Radiation therapy has been highly advanced as image guided radiation therapy
      (IGRT) by making advantage of image engineering technologies. Recently, novel
      frameworks based on image engineering technologies as well as machine learning
      technologies have been studied for sophisticating the radiation therapy. In this
      review paper, the author introduces several researches of applications of machine
      learning for radiation therapy. For examples, a method to determine the threshold
      values for standardized uptake value (SUV) for estimation of gross tumor volume
      (GTV) in positron emission tomography (PET) images, an approach to estimate the
      multileaf collimator (MLC) position errors between treatment plans and radiation
      delivery time, and prediction frameworks for esophageal stenosis and radiation
      pneumonitis risk after radiation therapy are described. Finally, the author
      introduces seven issues that one should consider when applying machine learning
      models to radiation therapy.

PMID- 28428496
TI  - Outcome Prediction after Radiotherapy with Medical Big Data.
AB  - Data science is becoming more important in many fields. In medical physics field,
      we are facing huge data every day. Treatment outcomes after radiation therapy are
      determined by complex interactions between clinical, biological, and dosimetrical
      factors. A key concept of recent radiation oncology research is to predict the
      outcome based on medical big data for personalized medicine. Here, some reports,
      which are analyzing medical databases with machine learning techniques, were
      reviewed and feasibility of outcome prediction after radiation therapy was
      discussed. In addition, some strategies for saving manual labors to analyze huge
      data in medical physics were discussed.

PMID- 28428497
TI  - Series: Practical Evaluation of Clinical Image Quality (2): Image Quality
      Measurements for Digital Radiography Systems.
AB  - In recent years, the manuals and data analysis tools to evaluate the basic
      imaging properties of medical imaging systems, such as digital radiography
      system, CT, and MRI, are easily available. For the image quality evaluation of
      digital radiography systems, special measurement system, such as a
      microdensitometer, required for the analysis of analog radiography system, is not
      needed. This enabled anyone to perform the evaluation of digital radiography
      system.On the other hand, to make accurate measurements, obtaining appropriate
      image data is a must. To enable this, appropriate setting of the hardware and the
      software is also required. In addition, we are asked to acquire sufficient
      knowledge to make highly reproducible measurements.

PMID- 28428498
TI  - Medical Applications of the PHITS Code (3): User Assistance Program for Medical
      Physics Computation.
AB  - DICOM2PHITS and PSFC4PHITS are user assistance programs for medical physics PHITS
      applications. DICOM2PHITS is a program to construct the voxel PHITS simulation
      geometry from patient CT DICOM image data by using a conversion table from CT
      number to material composition. PSFC4PHITS is a program to convert the IAEA phase
      space file data to PHITS format to be used as a simulation source of PHITS. Both
      of the programs are useful for users who want to apply PHITS simulation to
      verification of the treatment planning of radiation therapy. We are now
      developing a program to convert dose distribution obtained by PHITS to DICOM RT
      dose format. We also want to develop a program which is able to implement
      treatment information included in other DICOM files (RT-plan and RT-structure) as
      a future plan.

PMID- 28428499
TI  - Series: Utilization of Differential Equations and Methods for Solving Them in
      Medical Physics (4).
AB  - Partial differential equations are often used in the field of medical physics. In
      this (final) issue, the methods for solving the partial differential equations
      were introduced, which include separation of variables, integral transform
      (Fourier and Fourier-sine transforms), Green's function, and series expansion
      methods. Some examples were also introduced, in which the integral transform and
      Green's function methods were applied to solving Pennes' bioheat transfer
      equation and the Fourier series expansion method was applied to Navier-Stokes
      equation for analyzing the wall shear stress in blood vessels.Finally, the author
      hopes that this series will be helpful for people who engage in medical physics.

PMID- 28428500
TI  - Mini-lecture on X-ray Computed Tomography: Methods for Evaluating Radiation Dose.

PMID- 28428501
TI  - Job stress and behavioral characteristics in relation to coronary heart disease
      risk among Japanese police officers.
AB  - This study examined the association between job-related behavioral
      characteristics and the risk of coronary heart diseases (CHD) in Japanese male
      police officers. Compared to office clerks, police officers exhibited greater age
      related increases of the prevalence of CHD risk factors, and a clustering number
      of CHD risk factors was significantly higher in the group of those over 45 yr of
      age. Among the police officers, coronary-prone behavior was more frequent than
      that seen in office clerks. The police officers with coronary-prone behavior
      tended to engage in shift work and to work overtime more; yet they were less
      likely to perceive job stress and to express the relevant physical and
      psychological symptoms than those without coronary-prone behavior. The subjects
      with such behavioral characteristics had a significantly greater number of CHD
      risk factors. In a multiple regression analysis, coronary-prone behavior together
      with age, social support, walking hours per day, and amount of alcohol
      consumption were selected as significant determinants of a cluster of CHD risk
      factors. These results suggest that coronary-prone behavior may contribute to the
      higher prevalence of CHD risk factors in police officers via leading the long
      working hours and the work-related unfavorable lifestyles, such as alcohol
      drinking and physical inactivity.

PMID- 28428502
TI  - White-collar workers' hemodynamic responses during working hours.
AB  - In the present study, two investigations were conducted at a communication
      center, to examine white-collar workers' hemodynamic responses during working
      hours. In investigation I, hemodynamic responses were measured on a working day;
      and in investigation II, cardiovascular responses were verified on both working
      and non-working days. In investigation I, blood pressure, cardiac output, heart
      rate, stroke volume, and total peripheral resistance were measured in 15 workers
      during working hours (from 9:00 am to 18:00 pm) on one working day. Another 40
      workers from the same workplace participated in investigation II, in which blood
      pressure and heart rate were measured between the time workers arose in the
      morning until they went to bed on 5 working days and 2 non-working days. The
      results showed that blood pressure increased and remained at the same level
      during working hours. The underlying hemodynamics of maintaining blood pressure,
      however, changed between the morning and the afternoon on working days. Cardiac
      responses increased in the afternoon, suggesting that cardiac burdens increase in
      the afternoon on working days. The present study suggested that taking underlying
      hemodynamic response into consideration is important for managing the work
      related cardiovascular burden of white-collar workers.

PMID- 28428503
TI  - [Cancer Immunotherapy Utilizing T Cell Receptor Gene Engineering].
AB  - Immune-checkpoint inhibitors have shown their efficacy in the treatment of
      patients with many kinds of progressive/relapsed cancers. However, the efficacy
      remains as 10-40%of the patients in most type of cancers, suggesting that the
      development of new therapy for patients resistant to the therapy is an urgent
      unmet need. Adoptive therapy with tumor-specific T cells is a promising therapy
      that can be effective in patients who are not benefited from the immune
      checkpoint inhibitors. The T cell therapy with genetic engineering in T cell
      receptor(TCR)is expected to be a universal therapy because this therapy can be
      applicable for patients with many kinds of cancers. This review outlines the
      recent clinical development of cancer immunotherapy utilizing TCR-gene engineered
      T cells and discusses the issues that should be improved in the near future for
      the safer and more effective TCR-T cell therapy of the broad range of cancer
      patients.

PMID- 28428504
TI  - [Assessment and Strategy for Nociceptive Pain in Cancer].
AB  - Pain is classified as either nociceptive pain, which results from a nociceptor
      stimulation, or neuropathic pain, which results from a lesion of the neural
      pathway. Clinically, in many cases, pain consists of a single origin but multiple
      origins are also possible. In this paper, we outline an assessment and strategy
      for nociceptive pain in cancer. The onset time, location, feature, strength, and
      etiology were included as categories for the assessment of pain. Furthermore, we
      added a psychosocial assessment to the physical assessment, which ensured
      comprehensive pain evaluation. We performed the investigation according to the
      WHO method for cancer pain relief. According to the effects and adverse effects,
      we chose a non-opioid analgesic and an opioid analgesic as medications. However,
      nonpharmacological therapy, such as radiotherapy and nerve block, is not a
      concern with the WHO analgesic ladder. It is important that a multi-disciplinary
      team, which includes physicians, nurses, physiotherapists, and pharmacists,
      support the patients to manage their pain by themselves through the knowledge of
      the factors affecting their pain and the medication methods for easing it when it
      gets worse. Although we cannot ease pain completely, it is important to define
      the goal of treatment with patients and to examine the strategy for maximum pain
      relief.

PMID- 28428505
TI  - [Neurolysis and Spinal Analgesia in Cancer Pain Management].
AB  - Cancer pain appears as a complex pain and often progressive.WhenWHO pain
      management strategy and/or palliative care failed to relieve their pain, patients
      are given high dose opioids or anonymous adjuvant drugs and have no chance to
      meet specialized pain treatment. This section briefly covers the outline of
      neurolysis and spinal analgesia for these cancer patients with severe pain.
      Purpose of nerve block and neurolysis are to block the incoming signal of pain in
      order to reduce pain, reduce analgesic dose, recover ADL, and finally to be
      discharged from the hospital. However, autonomic nervous system, sensory nerves,
      and motor function could be impaired at the same time. Careful selection of
      candidate should be considered by the pain specialists. Spinal analgesia is
      indicated when, conservative pain treatment failed to reduce pain, wide range or
      multiple pain area, and when contraindicated for neurolysis. Epidural analgesia
      is preferred for in-hospital treatment and intrathecal analgesia for home care
      settings. Many cancer pain patients' life expectancy is not long enough to
      postpone the indication of these invasive techniques. If you seek to maintain
      patients' quality of life(QOL), one should consider these procedures at some
      point, although it may not be indicated.

PMID- 28428506
TI  - [A New Therapeutic Approach for Cancer-Related Breakthrough Pain - Focused on
      Oral Transmucosal Fentanyl].
AB  - In 2013, oral transmucosal fentanyl was first approved in Japan for reducing
      breakthrough pain(BTP). The development of BTP may contribute to less-effective
      analgesia, a reduced satisfaction with analgesia therapy, obstacles in daily
      life, mood disorders, and an increased use of healthcare resources. In most BTP,
      both the duration from BTP onset to its maximum intensity and the overall
      duration of BTP episodes are relatively short. The need for improved rapid pain
      relief for BTP in this setting has led to the development of rapid-onset
      opioids(ROOs), including oral transmucosal fentanyl citrate(OTFC). OTFC is
      characterized by a rapid onset and short duration of action. Therefore, the drug
      is optimally indicated for BTP in patients whose pain cannot be sufficiently
      controlled by the rapid-release preparation, and whose sleepiness due to the
      carry-over effect of analgesic action interferes with daily living. In addition,
      the drug can be used for patients who find it difficult to use oral preparations.
      Furthermore, since fentanyl is the main active ingredient, less severe side
      effects, such as constipation, are expected. OTFC may also be safely used for
      patients with renal dysfunction. Since the drug has many characteristics that
      differ from conventional rapid-release preparations, it is important to become
      familiar with the use of OTFC. In order to address improving the QOL of cancer
      patients, a comprehensive assessment of the patient, including the risk of BTP
      being inadequately controlled by conventional rescue preparations is necessary.

PMID- 28428507
TI  - [Opioid Therapy and Management of Side Effects Associated with Opioids].
AB  - Opioids are very useful medications to reduce suffering of cancer patients such
      as refractory pain and dyspnea. We physicians have to use opioids to have good
      management of pain and suffering associated with cancer including management of
      side effects caused by opioids. Opioids couple opioid receptors and affect
      several pharmacological effects. Other than analgesic effect, opioids have some
      side effects of constipation, nausea and vomiting, respiratory depression. In
      this chapter, I take important side effects of constipation, nausea and vomiting
      and respiratory depression. Next, serotonin syndrome caused by tramadol combined
      with anti-depressants is remarked as assignable syndrome. As advancing in
      chemotherapy for cancer treatment, cancer survivors live longer with opioid
      therapy. We have to pay attention to the side effects and another dysfunction
      caused by long use of opioids. It is important that we physician use opioids
      effectively to keep activity of daily living(ADL) of patients and families as
      team approach.

PMID- 28428508
TI  - [Melanoma and Non-Melanoma Skin Cancers].

PMID- 28428509
TI  - [I. Molecular Carcinogenesis of the Skin - An Update].

PMID- 28428510
TI  - [II. The Latest Treatment Strategy of the Melanoma - The Actual Situation in
      Japan].

PMID- 28428511
TI  - [III. Current Treatment Strategy for Cutaneous Angiosarcoma].

PMID- 28428512
TI  - [Change of Blood Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients
      with Metastatic Colorectal Cancer].
AB  - AIM: The impact of neutrophil-to-lymphocyte ratio(NLR)changes on the outcome of
      chemotherapy for metastatic colorectalcancer (mCRC)was analyzed retrospectively.
      METHODOLOGY: Twenty seven patients with unresectable mCRC were administered
      chemotherapy from January 2005 to December 2014 at the Niitsu Medical Center
      Hospital. The NLR was calculated from complete blood counts obtained prior to the
      administration of chemotherapy and at the best response. We defined the period
      with NLR<=2.5 as the totalintervalof NLR<=2.5. The impact of NLR on
      overallsurvivalwas determined using univariate and multivariate Cox regression
      models. RESULTS: The median overall survival was 26 months in patients with an
      NLR<=5(n= 22), and 11 months in those with an NLR>5(n=5)before
      chemotherapy(p=0.03). The median overall survival was 31 months in patients with
      an NLR<=2.5(n=19), and 11 months in those with an NLR>2.5(n=8)at the best
      response(p< 0.001). The period with an NLR<=2.5 was found to correlate with
      overall survival(p<0.001). The period with an NLR<=2.5 was the only independent,
      statistically significant predictor of better survival in multivariate
      analysis(p=0.001). CONCLUSION: The change of NLR may be a dynamic predictor of
      better survivalin patients with mCRC.

PMID- 28428513
TI  - [Comparison of Preparation Efficiency and Therapeutic Safety between Generic
      Products of Gemcitabine].
AB  - Because generic medicines reduce the financialburden on patients and
      medicalinsurance providers, they have become increasingly popular. However, there
      are only a few reports that have analyzed the efficacy and safety of generic
      medicines, especially in terms of their characteristics and side effects.
      Gemcitabine is an antineoplastic drug that is frequently used with good results
      in the treatment of lung cancer, pancreatic cancer, breast cancer, ovarian
      cancer, and malignant lymphoma. However, its fat solubility is high, and several
      adverse events, such as myelosuppression, are known to develop during its use. We
      investigated the efficacy, characteristics, and the incidence of adverse events
      for the generic versions of gemcitabine. We found differences between the generic
      versions in terms of the characteristics and preparation time; however, the
      incidence of adverse events was not significantly different, suggesting that the
      generic versions could be a reasonable substitute.

PMID- 28428514
TI  - [A Case Report of Disappearance of Gastric Metastasis of Breast Cancer Treated
      with Combination Therapy Consisting of Paclitaxel and Cisplatin].
AB  - A 63-year-old postmenopausal woman was treated with combination therapy
      consisting of paclitaxel(PTX)and cisplatin (CDDP)for gastric metastasis of breast
      cancer; she achieved a complete response as revealed by pathological examination.
      Combination therapy with PTX and CDDP seems to be an optional treatment for
      gastric metastasis of breast cancer.

PMID- 28428515
TI  - [A Case of Rhabdomyolysis Related to SOX Therapy for Liver Metastasis of Gastric
      Cancer].
AB  - We report a case of rhabdomyolysis related to S-1 plus oxaliplatin(SOX)therapy
      for liver metastasis of gastric cancer. A 76- year-old man who had received SOX
      therapy for metastatic gastric cancer was admitted to our hospital for a chief
      complaint of fatigue and weakness. He diagnosed with rhabdomyolysis related to
      SOX therapy because of his symptoms and because his laboratory studies showed
      significant elevation of his serum creatine kinase(CK)level. The symptoms
      disappeared and the CK level normalized following large-volume transfusions.
      Rhabdomyolysis following SOX therapy is a very rare, but severe adverse event.
      This is the first detailed case report of rhabdomyolysis related to SOX therapy.

PMID- 28428516
TI  - [Long-Term Survival of a Gastric Neuroendocrine Carcinoma Patient with Extra
      Regional Lymph Node Metastases].
AB  - A 56-year-old man with advanced gastric tumor in the pyloric antrum had multiple
      lymph node metastases(lymph nodes #5, 6, 8, and 13), as revealed by abdominal
      computed tomography(CT).The patient was diagnosed with coexisting clinical Stage
      III A gastric cancer(cT2[SS], cN2, cM0)with concomitant malignant lymphoma.Distal
      gastrectomy, D2 lymph node dissection, and resection of lymph node #13 were
      performed.Histopathological findings indicated that both the primary tumor and
      lymph node metastases were neuroendocrine carcinomas.Adjuvant chemotherapy with S
      1 was administered; however, follow-up CT after 6 months revealed local
      recurrence around the celiac artery.Therefore , the chemotherapy regimen was
      changed to irinotecan and cisplatin.A clinical complete response was obtained
      after 6 chemotherapy courses and maintained for up to 45 months.The patient is
      alive at 60 months after the operation.

PMID- 28428517
TI  - [A Hematogenous Metastasis from Scirrhous Gastric Cancer to the Uterus].
AB  - A 46-year-old woman was referred to our hospital because of nausea. Endoscopy
      revealed scirrhous gastric cancer, and abdominalcomputed tomography revealed
      peritonealdissemination. She was diagnosed with Stage IV gastric cancer and
      treated with S-1 plus CDDP combination chemotherapy. After 4 courses of
      chemotherapy, the primary tumor and peritoneal dissemination were considered
      clinically stable, but the uterus grew rapidly. She was diagnosed as having
      uterine metastasis based on cervicaland endometrialsmear class V cytology. As the
      chemotherapy was not effective for the uterine lesions, totalhysterectomy and
      bilateralsal pingo-oophorectomy were performed. Histological findings showed a
      poorly differentiated cancer with vascular emboli. Uterine metastases are an
      important consideration in women with scirrhous gastric cancer, and we recommend
      palliative hysterectomy for chemotherapy-resistant metastases if the primary
      tumor and other metastases are controlled.

PMID- 28428518
TI  - [A Case of Malignant Lymphoma of the Jejunum That Developed Stenosis and
      Perforation after a Complete Response to Chemotherapy].
AB  - A 57-year-old woman was admitted owing to epigastric pain.Abdominal computed
      tomography demonstrated a tumor in the origin of the jejunum.After an endoscopic
      biopsy, we diagnosed diffuse large B-cell lymphoma.We treated her with CHOP
      chemotherapy because pancreaticoduodenectomy is highly invasive.After 1 course of
      chemotherapy, the tumor was reduced.However, she developed a jejunal stenosis;
      therefore, we performed laparoscopic gastrojejunostomy.Furthermore, she developed
      perforated peritonitis on the sixth day after the surgery, and therefore, an
      emergency partial jejunum resection was performed.Histopathologically, viable
      lymphoma cells were not found in the resected intestine.She had a complete
      response 10 months after the surgery.Chemotherapy may cause intestinal stenosis
      and perforation requiring surgery; therefore, decisions about surgical procedures
      must be made carefully.

PMID- 28428519
TI  - [Current Status of Thoracic Endovascular Aortic Repair in Our Institution].
AB  - Within 8-year period between 2009 and 2016, we treated 215 patient with a
      strategy of primary thoracic endovascular aortic repair( TEVAR). In-hospital
      mortality was 4.4%( 8 cases). Thirty-two emergency cases was included and we
      treated 23 cases of zone 0 debranching TEVAR with chimney techinique in this
      period. In recent 2-year period between 2015 and 2016, we treated 44 cases of
      TEVAR without type I a endoleaks with 0% mortality(most of the them was zone 2~3
      TEVAR in this period) on the one hand, and the number of open surgery for
      thoracic aorta was 80 on the other. TEVAR was also indicated for emergency and
      high risk cases even if their anatomical conditions were outside of instruction
      for use, and utilized for bridging or staged therapy for open surgery in our
      series. Standardization and refinement of endovascular procedures is considered
      to be important to improvement outcomes, and hybrid therapy or back up of open
      surgery should be collaborated with TEVAR for thoracic aortic aneurysm treatment.

PMID- 28428520
TI  - [Prevention of Spinal Cord Ischemia During Thoracic Endovascular Aortic Repair].
AB  - Spinal cord ischemia(SCI) has been devastating complication of endovascular
      thoracic and thoracoabdominal aortic repair. Spinal cord blood supply arises from
      not only segmental artery, subclavian artery, hypogastric artery and these
      branches, but also perivertebral vasculature and paravertebral muscle and small
      arterial network, and risk factors of SCI were multifactorial. There are several
      adjuncts/strategies which are utilized to minimize the incidence of SCI:
      cerebrospinal fluid drainage, perioperative management of high mean arterial
      pressure, intraoperative evoked potential monitoring, and staged thoracoabdominal
      aortic repair. Recent developments including near-infrared spectroscopy,
      minimally invasive segmental artery coil embolization, and temporary aneurysm sac
      perfusion should be evaluated to prevent SCI.

PMID- 28428521
TI  - [Simple Evaluation of Left Hand Function after Thoracic Endovascular Aortic
      Repair with Obstruction of Left Subclavian Artery].
AB  - We evaluated left hand function with or without obstruction of left subclavian
      artery for 29 cases of thoracic endovascular aortic repair (TEVAR). 18 cases of
      distal true aortic aneurysm were undergone surgery with simple direct closure of
      left subclavian artery (LSCA). The other 11 cases of true arch aneurysm were
      revascularized by axilla-carotid-axilla bypass grafting with TEVAR. Later 26
      cases were evaluated by blood pressure, maximal grasping power, persisting
      duration of 60% maximal grasping power, circumferential length of upper and
      forearms, and simple test for evaluating hand function (STEF). Left hand blood
      pressure was significantly reduced than right side in obstruction group. But left
      hand function was not reduced in any other test. We concluded that no
      relationship between the obstruction of LSCA and the left hand function, and the
      influence of late survival and mobidity.

PMID- 28428522
TI  - [Surgeon-modified Fenestrated Thoracic Endovascular Aortic Repair for the
      Treatment of Aortic Aneurysm].
AB  - Thoracic endovascular aortic repair( TEVAR) for thoracic aortic aneurysm has been
      established as a 1st-line therapy, especially in high-risk cases, with device
      improvements and the appearance of various procedures, but there are still cases
      of anatomical adaptation. On the other hand, several countermeasures have been
      developed, but there are no commercially available devices for fenestrated or
      branched stent grafts in Japan. Moreover, complications such as cerebral
      infarction, organ ischemia and bypass occlusion and infection are pointed out in
      popular debranch TEVAR. However the surgeon-modified fenestrated TEVAR can extend
      the landing zone without open thoracotomy and laparotomy, and can reduce the
      operation time by decreasing debranch branches. And by the use of a commercially
      available device, is an urgent correspondence is possible surgical procedures. We
      report our treatment strategies including experience of 29 cases( Relay Plus:13
      cases, Cook TX2:16 cases) of surgeon-modified fenestrated TEVAR that we
      implemented.

PMID- 28428523
TI  - [Efficacy of Total Debranching Thoracic Endovascular Aortic Repair for the Re
      operation of Aortic Arch Aneurysm].
AB  - Thoracic endovascular aortic repair (TEVAR) combined with all-neck-branch
      reconstruction (total debranching TEVAR)[td TEVAR] is applied to aortic arch
      aneurysms as a minimally invasive procedure to improve treatment results. We
      report the initial and long-term results of td TEVAR for the reoperation of
      aortic arch aneurysm. By September 2016, td TEVAR for reoperation had been
      applied in 5 cases. The reasons for the reoperation were dilation of the arch
      aneurysm after ascending aorta replacement in 4 cases and localized dissection of
      the proximal landing zone after zone 2 TEVAR in 1 case. We reconstructed the neck
      branches under cardiopulmonary bypass (CPB). At that time, we kept in mind to
      perform anastomosis with an artificial graft at just above the sinus of Valsalva
      by using a single aortic clamp. Both the 30-day operative mortality and CPB
      related complication rates were 0%. One patient had paraparesis, and one had left
      upper limb ischemia. Our strategy of td TEVAR provided durable results in the
      patients who underwent reoperation for aortic arch aneurysms.

PMID- 28428524
TI  - [Hybrid Thoracic Endovascular Aortic Repair with Total Debranching of Supra
      aortic Trunks].
AB  - The method of hybrid arch thoracic endovascular aortic repair (TEVAR) to treat
      aneurysm with zone 0 landing has changed according to its invasiveness and
      complications. The real chimney technique allows supra-aortic bypass from
      ascending aorta without side clamp is the current choice of treatment. The
      comprehensive strategy to prevent stroke during hybrid arch TEVAR consisting of
      magnetization-prepared rapid acquisition with gradient-echo for evaluation of the
      atheromatous change and balloon protection of the left subclavian artery has
      contributed for the marked reduction of stroke. Our current strategy of hybrid
      arch TEVAR with zone 0 landing is discussed.

PMID- 28428525
TI  - [Total Arch Replacement Using Manufactured Frozen Elephant Trunk after Acute Type
      A Dissection Repair].
AB  - The purpose of this study is to assess the result of total arch replacement(TAR)
      using manufactured frozen elephant trunk(FET) for chronic aortic dissection after
      initial repair including the effect of aortic remodeling by the FET. Between 2003
      and 2015, we performed 11 TAR using manufactured FET. Initial repairs before were
      9 ascending aortic replacements and 2 Bentall operations. The entry of residual
      dissection was located at arch in 7 and at distal anastomosis site in 4. There
      was no hospital death. The operative complication included 2 surgical site
      infection, 1 interstitial pneumonia and 1 paraplegia with almost full recovery.
      Postoperative computed tomography 2.1 months after operation showed distal end of
      the FET was located at aortic valve level in 7 and at pulmonary bifurcation level
      in 4. There was no entry in thoracic aorta. Thrombosis of descending aorta was
      achieved in 7 patients. Significant midterm aortic remodeling (increased diameter
      of true lumen and decreased diameter of false lumen) was achieved, although the
      total diameter of aorta was increased. TAR using manufactured FET after type-A
      dissection repair promoted entry closure and thrombosis of false lumen. It
      requires long-term observation to judge the effect for aortic remodeling.

PMID- 28428526
TI  - [Strategy of Thoracic Endovascular Aortic Repair for Uncomplicated Type B Aortic
      Dissection in Subacute and Chronic Phase;Interval From Onset and Maximum
      Diameter].
AB  - We classified 59 patients who underwent thoracic endovascular aortic repair for
      uncomplicated type B aortic dissection from April 2008 to April 2016 into 3
      groups based on time from onset and maximum aortic diameter:SA (2weeks to 1 year
      since onset;n=29), C (>1 year since onset;n=17), and D(maximum aneurysm size>=60
      mm;n=13). We used the Kaplan-Meier method tso analyze survival, major adverse
      cardiovascular event and the need for additional treatment. There was no
      significant difference in outcomes between the SA and C groups (p=0.998) or C and
      D groups (p=0.279), but the results in group D tended to be consistently
      inferior. The freedom from aneurysm rupture rate was inferior in this group, with
      a significant difference between groups C and D (p=0.044). The time from onset to
      the procedure and maximum aortic diameter were not significantly associated with
      the longterm outcomes;however, more aortic ruptures occurred in the group with
      maximum aortic diameter>=60 mm. Simultaneous treatment for re-entry closure or
      conventional surgical procedures should be considered for such cases.

PMID- 28428527
TI  - [Treatment Strategy for Complicated Acute Type B Aortic Dissection in the
      Thoracic Endovascular Aortic Repair Era].
AB  - Our treatment strategy for acute type B aortic dissection (ABAD) included
      complicated type is as follows. Indications of thoracic endovascular aortic
      repair (TEVAR) for ABAD are rupture and organ ischemia, and TEVAR has been the
      1st line central repair therapy since January 2009 in our institution. At the
      time of TEVAR for ruptured communicating type ABAD, we usually seal the proximal
      entry tear and cover the existing range of hematoma at descending aorta.
      Procedures for ABAD with malperfusion should be changed according to the
      patient's condition such as branch vessel obstructions either dynamic type or
      static type. We select TEVAR for ABAD with malperfusion in order to prevent late
      aortic events as well as treat the dynamic malperfusion. For complicated ABAD
      patients with poor condition and hemodynamic instability, TEVAR achieving central
      repair rapidly and less-invasively is considered an advantageous procedure. We
      usually pay attention how to use TEVAR and how to combine with other therapies
      for complicated ABAD treatment.

PMID- 28428528
TI  - [Challenge of Treating Thoracoabdominal Aortic Aneurysms with Hybrid Thoracic
      Endovascular Aortic Repair].
AB  - The treatment of thoracoabdominal aortic aneurysms in great vessels is still
      challenging, as the early results of the operation are not very promising
      compared with other aortic operations, and the incidence of spinal cord ischemia
      is relatively high. In Japan, which is becoming a super-aging society, the method
      of performing minimally invasive operations remains a major issue. At our
      facility, we have been performing abdominal debranching thoracic endovascular
      aortic repair (TEVAR) to resolve these issues. Hybrid TEVAR was performed in 51
      cases of aortic aneurysm and chronic dissection of the thoracoabdominal field
      between 2007 and 2015. The standard operative procedure of abdominal debranching
      involves replacing the abdominal aorta with a bifurcated graft and making an
      anastomosis between the left leg of the bifurcated graft and a quadrifurcated
      graft;the visceral arteries are then reconstructed using the quadrifurcated
      graft. Abdominal debranching and TEVAR were performed as a 2-stage procedure.
      Hybrid repair of a thoracoabdominal aortic aneurysm is a good option for elderly,
      high-risk patients because the early and late results are acceptable.

PMID- 28428529
TI  - [Solitary Peripheral Pulmonary Squamous Cell Papilloma;Diagnostic Significance of
      18F-fluorodeoxyglucose Positron Emission Tomography Findings].
AB  - The patient was a 79-year-old woman who had received enucleation of right
      pulmonary papilloma 7 years earlier. She experienced bloody sputum and was
      therefore referred to our hospital. Chest computed tomography revealed a mass
      shadow(21 mm) in the right upper lobe (S2). By bronchoscopy, there was no bulging
      lesion in the visible range. SCC and CEA increased to 6.4 ng/ml and 6.42 ng/ml,
      respectively. Whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG
      PET) showed increased FDG uptake in the region of the right-lung mass shadow
      (maximum standardized uptake value 12.95). Since malignancy could not be ruled
      out, a wedge resection was performed. The post-operative histopathologic
      diagnosis was squamous cell papilloma. Our literature review showed 12 out of 14
      cases with solitary papilloma of the peripheral lung to have increased FDG
      uptake. Ki-67 positive cells were confirmed in the basal layers of the
      epithelium, and active cell proliferation of the papilloma is likely to be a
      cause of increased FDG uptake.

PMID- 28428530
TI  - [Duchenne Muscle Dystrophy Caused Bronchial Obstruction].
AB  - Duchenne muscle dystrophy (DMD), X-linked recessive genetic disorder, causes a
      variety of complications including scoliosis. We report a case of bronchial
      obstruction and hemorrhage caused by scoliosis with DMD. A man in his forties
      having been hospitalized due to DMD since the age of 6, produced bloody sputum. A
      chest X-ray showed atelectasis in his right lower lung. A computed tomography and
      bronchoscopy indicated that scoliosis and thoracic deformity due to muscle
      dystrophy caused compression of a right main bronchus by the vertebra, leading to
      bronchial obstruction and bleeding. We decided to follow closely without therapy
      because the bleeding had stopped as of the bronchoscopy. A high-risk surgery or
      bronchial stenting may be needed if he presents with severe bleeding or
      infection.

PMID- 28428531
TI  - [Effective Anticoagulation Therapy Prior to Surgical Excision of an Aortic Valve
      Papillary Fibroelastoma Diagnosed after a Transient Cerebral Ischemic
      Attack;Report of a Case].
AB  - Cardiac papillary fibroelastoma is reported to be the 2nd most common cardiac
      tumor following myxoma. Owing to the risk of embolism, early surgical excision is
      the treatment of choice. We report a case of effective anticoagulation therapy
      prior to surgical excision of an aortic valve papillary fibroelastoma. A 78-year
      old man was admitted to our hospital because of transient cerebral ischemic
      attack. The symptom was relieved in a short period. Echocardiography revealed a
      tumor at the aortic valve. Cardiac computed tomography revealed a sea-anemone
      like appearance of the tumor. Cardiac papillary fibroelastoma was suspected on
      close examination. The operation was postponed because of gingivitis that
      required draining. During 3 months awaiting the operation, he continued receiving
      anticoagulation therapy, which successfully prevented thromboembolism.
      Administration of anticoagulation therapy may be considered, unless early
      surgical excision can be performed.

PMID- 28428532
TI  - Ceftriaxone-Induced Hemolytic Anemia in a Jehovah's Witness.
AB  - BACKGROUND Drug-induced immune hemolytic anemia (DIIHA) is a rare condition that
      may result from the administration of an antibiotic, most notably the
      cephalosporin class, commonly used in both the adult and pediatric populations. A
      delay in recognition by a provider may lead to continuation of the offending
      agent and possibly result in fatal outcomes. CASE REPORT We report the case of a
      65-year-old woman on ceftriaxone infusions after being diagnosed with acute
      mitral valve endocarditis 3 weeks prior, which presented with severe anemia and
      bilateral transient vision loss. Being a Jehovah's Witness, the patient refused
      blood product transfusions and was managed with alternative therapies. The
      etiology of the symptoms was suspected to be a hemolytic anemia directly related
      to her ceftriaxone infusions. CONCLUSIONS This report demonstrates the importance
      of close vigilance while prescribing drugs known to cause hemolytic anemia.
      Although rare, drug-induced immune hemolytic anemia caused by ceftriaxone may be
      a potentially fatal condition, but with early recognition and withdrawal of the
      offending agent, successful treatment may ensue. Serological tests should be
      utilized to obtain a definitive diagnosis.

PMID- 28428533
TI  - Protective Effect of Tempol Against Hypoxia-Induced Oxidative Stress and
      Apoptosis in H9c2 Cells.
AB  - Background Material and Methods Results Conclusions.

PMID- 28428534
TI  - Expression of Acid-Sensing Ion Channels in Renal Tubular Epithelial Cells and
      Their Role in Patients with Henoch-Schonlein Purpura Nephritis.
AB  - BACKGROUND Acid-sensing ion channels (ASICs) are ligand-gated cation channels
      activated by extracellular protons. However, the role of ASICs in kidney diseases
      remains uncertain. This study investigated ASICs expression in kidney tissues and
      their role in the development of Henoch-Schonlein purpura nephritis (HSPN).
      MATERIAL AND METHODS The expression of ASIC subunits was examined by
      immunochemical techniques in the kidney tissue from HSPN patients. Acid-induced
      ASICs expression in cultured renal tubular epithelial cells was determined by
      quantitative RT-PCR analysis. The expression of K7 and K18 protein in renal
      tubular epithelial cells was used to evaluate acid-induced cell injury. In
      addition, we observed the effect of blocking ASICs on acid-induced cell injury to
      assess the role of ASICs in renal tubular epithelial cell injury. RESULTS The
      results showed that ASIC1, ASIC2, and ASIC3 proteins were obviously expressed in
      renal tubular cells from HSPN patients. ASIC1 expression and 24-h urine protein
      level were higher in the pathological grade ISKD III group than in the ISKD II
      group. ASIC1, ASIC2, and ASIC3 mRNA, and K7 and K18 protein expression in
      cultured renal tubular epithelial cells were increased when exposed to pH 6.5. K7
      and K18 protein expression was closely related to ASIC1 expression, and ASICs
      blockers reduced K7 and K18 protein expression in tubular epithelial cells.
      CONCLUSIONS These findings suggest ASICs are most highly expressed in renal
      tubular cells of HSPN patients, which is closely related to renal tubular injury.
      ASICs might be involved in the development of HSPN.

PMID- 28428535
TI  - In Situ Split Liver Transplantation for 2 Adult Recipients: A Single-Center
      Experience.
AB  - Background Material and Methods Results Conclusions.

PMID- 28428536
TI  - Real-time observation of interfacial ions during electrocrystallization.
AB  - Understanding the electrocrystallization mechanisms of metal cations is of
      importance for many industrial and scientific fields. We have determined the
      transitional structures during underpotential deposition (upd) of various metal
      cations on Au(111) electrode using time-resolved surface X-ray diffraction and
      step-scan IR spectroscopy. At the initial stage of upd, a characteristic
      intensity transient appears in the time-resolved crystal truncation rod depending
      on metal cations. Metal cations with relatively high coordination energies of
      hydration water are deposited in two steps: first, the hydrated metal cations
      approached the surface and are metastably located at the outer Helmholtz plane,
      then they are deposited via the destruction of the hydration shell. However, Tl+
      and Ag+, which have low hydration energy, are rapidly adsorbed on Au(111)
      electrode without any metastable states of dehydration. Therefore, the deposition
      rate is strongly related to the coordination energy of the hydration water. Metal
      cations strongly interacting with the counter coadsorbed anions such as Cu2+ in
      sulfuric acid causes the deposition rate to be slower because of the formation of
      complexes.

PMID- 28428537
TI  - Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune
      Responses in Humanized BLT Mice.
AB  - The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our
      understanding of antiviral adaptive immune responses in the context of a human
      immune system. We have previously shown that HCMV infection of human
      hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results
      in viral latency that can be reactivated following G-CSF treatment. In this
      study, we characterized the functional human adaptive immune responses in HCMV
      latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice. Following
      infection, huBLT mice generate human effector and central memory CD4+ and CD8+ T
      cell responses reactive to peptides corresponding to both IE and pp65 proteins.
      Additionally, both HCMV specific IgM and IgG B-cell responses with the ability to
      neutralize virus were detected. These results indicate that the HCMV huBLT mouse
      model may provide a valuable tool to study viral latency and reactivation as well
      as evaluate HCMV vaccines and immune responses in the context of a functional
      human immune system.

PMID- 28428538
TI  - Hyperuricemia is associated with cardiovascular diseases clustering among very
      elderly women - a community based study in Chengdu, China.
AB  - Cardiovascular epidemiological features among very elderly Chinese are still
      uncertain. This study aimed to describe the distribution of cardiovascular
      diseases and sex difference, and investigate potential risk factors for diseases
      clustering among very elderly Chinese. From May 2013 to May 2015, a total of 1056
      very elderly were sampled in this cross-sectional study. Demographic
      characteristics collection, physical examination and biochemical analysis were
      performed. Totally, 1038 participants (men: 49.8%) with a median age of 83.0
      years (age range: 80.0-100.0 years) were included. In this very elderly group,
      the prevalences of hypertension, diabetes mellitus, renal dysfunction,
      hyperuricemia, obesity, visceral obesity, and hypercholesterolaemia were 76.9%,
      20.0%, 23.3%, 33.0%, 9.4%, 54.5% and 35.8%, respectively. About 17.5% of very
      elderly (men vs. women: 15.1% vs 19.8%, p = 0.007) have >=3 cardiovascular
      diseases clustering. Logistic analysis found that hyperuricemia (odds ratio
      3.850, 95%CI 2.189-6.770) was associated with of cardiovascular diseases
      clustering among very elderly women. Prevalences of prehypertension,
      hyperuricemia, visceral obesity and dyslipidaemia are apparent in very elderly
      women, while diabetes mellitus, renal dysfunction are common in very elderly men.
      Women are more likely to have >=3 cardiovascular diseases. Hyperuricemia is
      associated with cardiovascular diseases clustering among very elderly women.

PMID- 28428539
TI  - Separating decadal global water cycle variability from sea level rise.
AB  - Under a warming climate, amplification of the water cycle and changes in
      precipitation patterns over land are expected to occur, subsequently impacting
      the terrestrial water balance. On global scales, such changes in terrestrial
      water storage (TWS) will be reflected in the water contained in the ocean and can
      manifest as global sea level variations. Naturally occurring climate-driven TWS
      variability can temporarily obscure the long-term trend in sea level rise, in
      addition to modulating the impacts of sea level rise through natural periodic
      undulation in regional and global sea level. The internal variability of the
      global water cycle, therefore, confounds both the detection and attribution of
      sea level rise. Here, we use a suite of observations to quantify and map the
      contribution of TWS variability to sea level variability on decadal timescales.
      In particular, we find that decadal sea level variability centered in the Pacific
      Ocean is closely tied to low frequency variability of TWS in key areas across the
      globe. The unambiguous identification and clean separation of this component of
      variability is the missing step in uncovering the anthropogenic trend in sea
      level and understanding the potential for low-frequency modulation of future TWS
      impacts including flooding and drought.

PMID- 28428540
TI  - Temporal dynamics of saccades explained by a self-paced process.
AB  - Sensory organs are thought to sample the environment rhythmically thereby
      providing periodic perceptual input. Whisking and sniffing are governed by
      oscillators which impose rhythms on the motor-control of sensory acquisition and
      consequently on sensory input. Saccadic eye movements are the main visual
      sampling mechanism in primates, and were suggested to constitute part of such a
      rhythmic exploration system. In this study we characterized saccadic rhythmicity,
      and examined whether it is consistent with autonomous oscillatory generator or
      with self-paced generation. Eye movements were tracked while observers were
      either free-viewing a movie or fixating a static stimulus. We inspected the
      temporal dynamics of exploratory and fixational saccades and quantified their
      first-order and high-order dependencies. Data were analyzed using methods derived
      from spike-train analysis, and tested against mathematical models and
      simulations. The findings show that saccade timings are explained by first-order
      dependencies, specifically by their refractory period. Saccade-timings are
      inconsistent with an autonomous pace-maker but are consistent with a "self-paced"
      generator, where each saccade is a link in a chain of neural processes that
      depend on the outcome of the saccade itself. We propose a mathematical model
      parsimoniously capturing various facets of saccade-timings, and suggest a
      possible neural mechanism producing the observed dynamics.

PMID- 28428541
TI  - Tissue-engineered cornea constructed with compressed collagen and laser
      perforated electrospun mat.
AB  - While Plastic Compressed (PC) collagen technique is often used to fabricate
      bioengineered constructs, PC collagen gels are too weak to be sutured or
      conveniently handled for clinical applications. To overcome this limitation,
      electrospun poly (lactic-co-glycolide) (PLGA) mats, which have excellent
      biocompatibility and mechanical properties, were combined with PC collagen to
      fabricate sandwich-like hybrid constructs. By laser-perforating holes with
      different sizes and spacings in the electrospun mats to regulate the mechanical
      properties and light transmittance of the hybrid constructs, we produced hybrid
      constructs with properties very suitable to apply in corneal tissue engineering.
      The maximum tensile stress of the optimal hybrid construct was 3.42 +/- 0.22 MPa.
      The light transmittance of the hybrid construct after perforation was
      approximately 15-fold higher than before, and light transmittance increased
      gradually with increasing time. After immersing into PBS for 7 days, the
      transmittance of the optimal construct changed from 63 +/- 2.17% to 72 +/- 1.8%
      under 500 nm wavelength. The live/dead staining, cell proliferation assay and
      immunohistochemistry study of human corneal epithelial cells (HCECs) and human
      keratocytes (HKs) cultured on the optimal hybrid construct both demonstrated that
      the cells adhered, proliferated, and maintained their phenotype well on the
      material. In addition, after culturing for 2 weeks, the HCECs could form
      stratified layers. Thus, our designed construct is suitable for the construction
      of engineered corneal tissue.

PMID- 28428542
TI  - Poly-protein G-expressing bacteria enhance the sensitivity of immunoassays.
AB  - The sensitivities of solid-phase immunoassays are limited by the quantity of
      detection antibodies bound to their antigens on the solid phase. Here, we
      developed a poly-protein G-expressing bacterium as an antibody-trapping
      microparticle to enhance the signals of immunoassays by increasing the
      accumulation of detection antibodies on the given antigen. Eight tandemly
      repeated fragment crystallisable (Fc) binding domains of protein G were stably
      expressed on the surface of Escherichia coli BL21 cells (termed BL21/8G). BL21/8G
      cells showed a higher avidity for trapping antibodies on their surface than
      monomeric protein G-expressing BL21 (BL21/1G) cells did. In the sandwich enzyme
      linked immunosorbent assay (ELISA), simply mixing the detection antibody with
      BL21/8G provided a detection limit of 6 pg/mL for human interferon-alpha (IFN
      alpha) and a limit of 30 pg/mL for polyethylene glycol (PEG)-conjugated IFN-alpha
      (Pegasys), which are better than that of the traditional ELISA (30 pg/mL for IFN
      alpha and 100 pg/mL for Pegasys). Moreover, the sensitivity of the Western blot
      for low-abundance Pegasys (0.4 ng/well) was increased by 25 folds upon mixing of
      an anti-PEG antibody with BL21/8G cells. By simply being mixed with a detection
      antibody, the poly-protein G-expressing bacteria can provide a new method to
      sensitively detect low-abundance target molecules in solid-phase immunoassays.

PMID- 28428543
TI  - Microspectrofluorimetry to dissect the permeation of ceftazidime in Gram-negative
      bacteria.
AB  - A main challenge in chemotherapy is to determine the in cellulo parameters
      modulating the drug concentration required for therapeutic action. It is
      absolutely urgent to understand membrane permeation and intracellular
      concentration of antibiotics in clinical isolates: passing the membrane barrier
      to reach the threshold concentration inside the bacterial periplasm or cytoplasm
      is the pivotal step of antibacterial activity. Ceftazidime (CAZ) is a key
      molecule of the combination therapy for treating resistant bacteria. We designed
      and synthesized different fluorescent CAZ derivatives (CAZ*, CAZ**) to dissect
      the early step of translocation-accumulation across bacterial membrane. Their
      activities were determined on E. coli strains and on selected clinical isolates
      overexpressing beta-lactamases. The accumulation of CAZ* and CAZ** were
      determined by microspectrofluorimetry and epifluorimetry. The derivatives were
      properly translocated to the periplasmic space when we permeabilize the outer
      membrane barrier. The periplasmic location of CAZ** was related to a significant
      antibacterial activity and with the outer membrane permeability. This study
      demonstrated the correlation between periplasmic accumulation and antibiotic
      activity. We also validated the method for approaching beta-lactam permeation
      relative to membrane permeability and paved the way for an original matrix for
      determining "Structure Intracellular Accumulation Activity Relationship" for the
      development of new therapeutic candidates.

PMID- 28428544
TI  - Strain softening of nano-scale fuzzy interfaces causes Mullins effect in
      thermoplastic polyurethane.
AB  - The strain-induced softening of thermoplastic polyurethane elastomers (TPUs),
      known as the Mullins effect, arises from their multi-phase structure. We used the
      combination of small- and wide- angle X-ray scattering (SAXS/WAXS) during in situ
      repeated tensile loading to elucidate the relationship between molecular
      architecture, nano-strain, and macro-scale mechanical properties. Insights
      obtained from our analysis highlight the importance of the 'fuzzy interface'
      between the hard and soft regions that governs the structure evolution at
      nanometre length scales and leads to macroscopic stiffness reduction. We propose
      a hierarchical Eshelby inclusion model of phase interaction mediated by the
      'fuzzy interface' that accommodates the nano-strain gradient between hard and
      soft regions and undergoes tension-induced softening, causing the Mullins effect
      that becomes apparent in TPUs even at moderate tensile strains.

PMID- 28428545
TI  - Beclin-1-mediated Autophagy Protects Against Cadmium-activated Apoptosis via the
      Fas/FasL Pathway in Primary Rat Proximal Tubular Cell Culture.
AB  - The Fas/FasL signaling pathway is one of the primary apoptosis pathways, but the
      involvement and regulatory mechanism of this pathway by autophagy remain unclear.
      Here we demonstrated that cadmium (Cd) activated the Fas/FasL apoptosis pathway
      in rat proximal tubular (rPT) cells; this was accompanied by simultaneous
      activation of autophagy resulted in reduced apoptosis. In this model, we induced
      autophagy through RAPA and further demonstrated that autophagy protects against
      activation of Fas/FasL signaling and apoptosis. The antiapoptotic effect of
      autophagy was blocked by 3-MA, an autophagy inhibitor. The interactions between
      Beclin-1 and Fas, FasL, FADD, caspase-8 and BID/tBID were relatively weak, with
      the exception of cleaved caspase-8, indicated that minimal interactions between
      these proteins and Beclin-1 are involved in maintaining the balance of autophagy
      and apoptosis. Beclin-1 precipitated with cleaved caspase-8 in a dose-dependent
      mannter, and the expression was increased by siRNA against Beclin-1. These data
      suggested that Beclin-1-mediated autophagy impairs the expression and function of
      cleaved caspase-8 to protect against Cd-induced activation of apopotosis through
      Fas/FasL signaling pathway.

PMID- 28428546
TI  - Influence of intermixing at the Ta/CoFeB interface on spin Hall angle in
      Ta/CoFeB/MgO heterostructures.
AB  - When a current is passed through a non-magnetic metal with strong spin-orbit
      coupling, an orthogonal spin current is generated. This spin current can be used
      to switch the magnetization of an adjacent ferromagnetic layer or drive its
      magnetization into continuous precession. The interface, which is not necessarily
      sharp, and the crystallographic structure of the nonmagnetic metal can both
      affect the strength of current-induced spin-orbit torques. Here, we investigate
      the effects of interface intermixing and film microstructure on spin-orbit
      torques in perpendicularly magnetized Ta/Co40Fe40B20/MgO trilayers with different
      Ta layer thickness (5 nm, 10 nm, 15 nm), greater than the spin diffusion length.
      Effective spin-orbit torques are determined from harmonic Hall voltage
      measurements performed at temperatures ranging from 20 K to 300 K. We account for
      the temperature dependence of damping-like and field-like torques by including an
      additional contribution from the Ta/CoFeB interface in the spin diffusion model.
      Using this approach, the temperature variations of the spin Hall angle in the Ta
      underlayer and at the Ta/CoFeB interface are determined separately. Our results
      indicate an almost temperature-independent spin Hall angle of [Formula: see text]
      in Ta and a strongly temperature-dependent [Formula: see text] for the intermixed
      Ta/CoFeB interface.

PMID- 28428547
TI  - The tarantula toxin beta/delta-TRTX-Pre1a highlights the importance of the S1-S2
      voltage-sensor region for sodium channel subtype selectivity.
AB  - Voltage-gated sodium (NaV) channels are essential for the transmission of pain
      signals in humans making them prime targets for the development of new
      analgesics. Spider venoms are a rich source of peptide modulators useful to study
      ion channel structure and function. Here we describe beta/delta-TRTX-Pre1a, a 35
      residue tarantula peptide that selectively interacts with neuronal NaV channels
      inhibiting peak current of hNaV1.1, rNaV1.2, hNaV1.6, and hNaV1.7 while
      concurrently inhibiting fast inactivation of hNaV1.1 and rNaV1.3. The DII and DIV
      S3-S4 loops of NaV channel voltage sensors are important for the interaction of
      Pre1a with NaV channels but cannot account for its unique subtype selectivity.
      Through analysis of the binding regions we ascertained that the variability of
      the S1-S2 loops between NaV channels contributes substantially to the selectivity
      profile observed for Pre1a, particularly with regards to fast inactivation. A
      serine residue on the DIV S2 helix was found to be sufficient to explain Pre1a's
      potent and selective inhibitory effect on the fast inactivation process of NaV1.1
      and 1.3. This work highlights that interactions with both S1-S2 and S3-S4 of NaV
      channels may be necessary for functional modulation, and that targeting the
      diverse S1-S2 region within voltage-sensing domains provides an avenue to develop
      subtype selective tools.

PMID- 28428549
TI  - Low-noise time-resolved optical sensing of electromagnetic pulses from petawatt
      laser-matter interactions.
AB  - We report on the development and deployment of an optical diagnostic for single
      shot measurement of the electric-field components of electromagnetic pulses from
      high-intensity laser-matter interactions in a high-noise environment. The electro
      optic Pockels effect in KDP crystals was used to measure transient electric
      fields using a geometry easily modifiable for magnetic field detection via
      Faraday rotation. Using dielectric sensors and an optical fibre-based readout
      ensures minimal field perturbations compared to conductive probes and greatly
      limits unwanted electrical pickup between probe and recording system. The device
      was tested at the Vulcan Petawatt facility with 1020 W cm-2 peak intensities, the
      first time such a diagnostic has been used in this regime. The probe crystals
      were located ~1.25 m from target and did not require direct view of the source
      plasma. The measured signals compare favourably with previously reported studies
      from Vulcan, in terms of the maximum measured intra-crystal field of 10.9 kV/m,
      signal duration and detected frequency content which was found to match the
      interaction chamber's horizontal-plane fundamental harmonics of 76 and 101 MHz.
      Methods for improving the diagnostic for future use are also discussed in detail.
      Orthogonal optical probes offer a low-noise alternative for direct simultaneous
      measurement of each vector field component.

PMID- 28428548
TI  - Antiviral activities of Schizonepeta tenuifolia Briq. against enterovirus 71 in
      vitro and in vivo.
AB  - No effective drug is currently available for treatment of enterovirus 71 (EV71)
      infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal
      constituent of traditional Chinese medicine. We studied whether the aqueous
      extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE
      inhibited replication of EV71, as evident by its ability to diminish plaque
      formation and cytopathic effect induced by EV71, and to inhibit the synthesis of
      viral RNA and protein. Moreover, daily single-dose STE treatment significantly
      improved the survival of EV71-infected mice, and ameliorated the symptoms.
      Mechanistically, STE exerts multiple effects on enteroviral infection. Treatment
      with STE reduced viral attachment and entry; the cleavage of eukaryotic
      translation initiation factor 4 G (eIF4G) by EV71 protease, 2Apro; virus-induced
      reactive oxygen species (ROS) formation; and relocation of heterogeneous nuclear
      ribonucleoprotein A1 (hnRNP A1) from the nucleus to the cytoplasm. It was
      accompanied by a decline in EV71-associated hyperphosphorylation of p38 kinase
      and EPS15. It is plausible that STE may inhibit ROS-induced p38 kinase
      activation, and subsequent hnRNP A1 relocation and EPS15-mediated membrane
      trafficking in infected cells. These findings suggest that STE possesses anti
      EV71 activities, and may serve as health food or candidate antiviral drug for
      protection against EV71.

PMID- 28428550
TI  - Structure-based dynamic arrays in regulatory domains of sodium-calcium exchanger
      (NCX) isoforms.
AB  - Mammalian Na+/Ca2+ exchangers, NCX1 and NCX3, generate splice variants, whereas
      NCX2 does not. The CBD1 and CBD2 domains form a regulatory tandem (CBD12), where
      Ca2+ binding to CBD1 activates and Ca2+ binding to CBD2 (bearing the splicing
      segment) alleviates the Na+-induced inactivation. Here, the NCX2-CBD12, NCX3
      CBD12-B, and NCX3-CBD12-AC proteins were analyzed by small-angle X-ray scattering
      (SAXS) and hydrogen-deuterium exchange mass-spectrometry (HDX-MS) to resolve
      regulatory variances in the NCX2 and NCX3 variants. SAXS revealed the unified
      model, according to which the Ca2+ binding to CBD12 shifts a dynamic equilibrium
      without generating new conformational states, and where more rigid conformational
      states become more populated without any global conformational changes. HDX-MS
      revealed the differential effects of the B and AC exons on the folding stability
      of apo CBD1 in NCX3-CBD12, where the dynamic differences become less noticeable
      in the Ca2+-bound state. Therefore, the apo forms predefine incremental changes
      in backbone dynamics upon Ca2+ binding. These observations may account for slower
      inactivation (caused by slower dissociation of occluded Ca2+ from CBD12) in the
      skeletal vs the brain-expressed NCX2 and NCX3 variants. This may have
      physiological relevance, since NCX must extrude much higher amounts of Ca2+ from
      the skeletal cell than from the neuron.

PMID- 28428551
TI  - Enhanced visible light photocatalytic performance of CdS sensitized TiO2 nanorod
      arrays decorated with Au nanoparticles as electron sinks.
AB  - In this paper, we propose a nanostructure with Au nanoparticles (NPs), as
      electron sinks, located at the most outside layer of CdS sensitized TiO2 nanorod
      arrays (TiO2 NRAs/CdS/Au). By the introduction of Au NPs, TiO2 NRAs/CdS/Au
      performs higher visible light photocatalytic capacity in the degradation of
      unsymmetrical dimethylhydrazine wastewater than TiO2 NRAs/CdS. The optimal
      deposition time for Au NPs is 30 s. The visible light induced degradation ability
      of TiO2 NRAs/CdS/Au (30 s) is 1.4 times that of TiO2 NRAs/CdS. The cycling
      stability of TiO2 NRAs/CdS is greatly enchanced after Au NPs decoration, which
      can maintain 95.86% after three cycles. Photoluminescence spectra and
      photoelectrochemical measurements were carried out to reveal the underlying
      mechanism for the improved visible light photocatalytic capacity of TiO2
      NRAs/CdS/Au. This work demonstrates a promising way for the rational design of
      metal-semiconductor photocatalysts used in decomposition reaction that can
      achieve high photocatalytic efficiency.

PMID- 28428552
TI  - Divergent copies of the large inverted repeat in the chloroplast genomes of
      ulvophycean green algae.
AB  - The chloroplast genomes of many algae and almost all land plants carry two
      identical copies of a large inverted repeat (IR) sequence that can pair for flip
      flop recombination and undergo expansion/contraction. Although the IR has been
      lost multiple times during the evolution of the green algae, the underlying
      mechanisms are still largely unknown. A recent comparison of IR-lacking and IR
      containing chloroplast genomes of chlorophytes from the Ulvophyceae
      (Ulotrichales) suggested that differential elimination of genes from the IR
      copies might lead to IR loss. To gain deeper insights into the evolutionary
      history of the chloroplast genome in the Ulvophyceae, we analyzed the genomes of
      Ignatius tetrasporus and Pseudocharacium americanum (Ignatiales, an order not
      previously sampled), Dangemannia microcystis (Oltmannsiellopsidales),
      Pseudoneochloris marina (Ulvales) and also Chamaetrichon capsulatum and
      Trichosarcina mucosa (Ulotrichales). Our comparison of these six chloroplast
      genomes with those previously reported for nine ulvophyceans revealed unsuspected
      variability. All newly examined genomes feature an IR, but remarkably, the copies
      of the IR present in the Ignatiales, Pseudoneochloris, and Chamaetrichon diverge
      in sequence, with the tRNA genes from the rRNA operon missing in one IR copy. The
      implications of this unprecedented finding for the mechanism of IR loss and flip
      flop recombination are discussed.

PMID- 28428553
TI  - The yeast osmostress response is carbon source dependent.
AB  - Adaptation to altered osmotic conditions is a fundamental property of living
      cells and has been studied in detail in the yeast Saccharomyces cerevisiae. Yeast
      cells accumulate glycerol as compatible solute, controlled at different levels by
      the High Osmolarity Glycerol (HOG) response pathway. Up to now, essentially all
      osmostress studies in yeast have been performed with glucose as carbon and energy
      source, which is metabolised by glycolysis with glycerol as a by-product. Here we
      investigated the response of yeast to osmotic stress when yeast is respiring
      ethanol as carbon and energy source. Remarkably, yeast cells do not accumulate
      glycerol under these conditions and it appears that trehalose may partly take
      over the role as compatible solute. The HOG pathway is activated in very much the
      same way as during growth on glucose and is also required for osmotic adaptation.
      Slower volume recovery was observed in ethanol-grown cells as compared to glucose
      grown cells. Dependence on key regulators as well as the global gene expression
      profile were similar in many ways to those previously observed in glucose-grown
      cells. However, there are indications that cells re-arrange redox-metabolism when
      respiration is hampered under osmostress, a feature that could not be observed in
      glucose-grown cells.

PMID- 28428554
TI  - Network-assisted analysis of GWAS data identifies a functionally-relevant gene
      module for childhood-onset asthma.
AB  - The number of genetic factors associated with asthma remains limited. To identify
      new genes with an undetected individual effect but collectively influencing
      asthma risk, we conducted a network-assisted analysis that integrates outcomes of
      genome-wide association studies (GWAS) and protein-protein interaction networks.
      We used two GWAS datasets, each consisting of the results of a meta-analysis of
      nine childhood-onset asthma GWASs (5,924 and 6,043 subjects, respectively). We
      developed a novel method to compute gene-level P-values (fastCGP), and proposed a
      parallel dense-module search and cross-selection strategy to identify an asthma
      associated gene module. We identified a module of 91 genes with a significant
      joint effect on childhood-onset asthma (P < 10-5). This module contained a core
      subnetwork including genes at known asthma loci and five peripheral subnetworks
      including relevant candidates. Notably, the core genes were connected to APP
      (encoding amyloid beta precursor protein), a major player in Alzheimer's disease
      that is known to have immune and inflammatory components. Functional analysis of
      the module genes revealed four gene clusters involved in innate and adaptive
      immunity, chemotaxis, cell-adhesion and transcription regulation, which are
      biologically meaningful processes that may underlie asthma risk. Our findings
      provide important clues for future research into asthma aetiology.

PMID- 28428555
TI  - Application of high resolution melting assay (HRM) to study temperature-dependent
      intraspecific competition in a pathogenic bacterium.
AB  - Studies on species' responses to climate change have focused largely on the
      direct effect of abiotic factors and in particular temperature, neglecting the
      effects of biotic interactions in determining the outcome of climate change
      projections. Many microbes rely on strong interference competition; hence the
      fitness of many pathogenic bacteria could be a function of both their growth
      properties and intraspecific competition. However, due to technical challenges in
      distinguishing and tracking individual strains, experimental evidence on
      intraspecific competition has been limited so far. Here, we developed a robust
      application of the high-resolution melting (HRM) assay to study head-to-head
      competition between mixed genotype co-cultures of a waterborne bacterial pathogen
      of fish, Flavobacterium columnare, at two different temperatures. We found that
      competition outcome in liquid cultures seemed to be well predicted by growth
      yield of isolated strains, but was mostly inconsistent with interference
      competition results measured in inhibition tests on solid agar, especially as no
      growth inhibition between strain pairs was detected at the higher temperature.
      These results suggest that, for a given temperature, the factors driving
      competition outcome differ between liquid and solid environments.

PMID- 28428556
TI  - Treatment of donor corneal tissue with immunomodulatory cytokines: a novel
      strategy to promote graft survival in high-risk corneal transplantation.
AB  - Antigen-presenting cells (APCs) play an important role in transplant rejection
      and tolerance. In high-risk corneal transplantation, where the graft bed is
      inflamed and vascularized, immature APCs in the donor corneal stroma quickly
      mature and migrate to lymphoid tissues to sensitize host T cells. In this study,
      using a mouse model of corneal transplantation, we investigated whether
      enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft
      survival in corneal allograft recipients with inflamed graft beds. Treatment of
      donor corneas with interleukin-10 (IL-10) and transforming growth factor-beta1
      (TGFbeta1) altered the phenotype and function of tissue-residing APCs.
      Transplantation of these tolAPC-enriched corneas decreased frequencies of
      interferon gamma (IFNgamma)+ effector T cells (Teffs), as well as
      allosensitization in the hosts, diminished graft infiltration of CD45+ and CD4+
      cells, and significantly improved corneal allograft survival compared to saline
      injected controls. These data provide a novel approach for tolAPC-based
      immunotherapy in transplantation by direct cytokine conditioning of the donor
      tissue.

PMID- 28428557
TI  - The prognostic significance of Cdc6 and Cdt1 in breast cancer.
AB  - DNA replication is a critical step in cell proliferation. Overexpression of MCM2
      7 genes correlated with poor prognosis in breast cancer patients. However, the
      roles of Cdc6 and Cdt1, which work with MCMs to regulate DNA replication, in
      breast cancers are largely unknown. In the present study, we have shown that the
      expression levels of Cdc6 and Cdt1 were both significantly correlated with an
      increasing number of MCM2-7 genes overexpression. Both Cdc6 and Cdt1, when
      expressed in a high level, alone or in combination, were significantly associated
      with poorer survival in the breast cancer patient cohort (n = 1441). In line with
      this finding, the expression of Cdc6 and Cdt1 was upregulated in breast cancer
      cells compared to normal breast epithelial cells. Expression of Cdc6 and Cdt1 was
      significantly higher in ER negative breast cancer, and was suppressed when ER
      signalling was inhibited either by tamoxifen in vitro or letrozole in human
      subjects. Importantly, breast cancer patients who responded to letrozole
      expressed significantly lower Cdc6 than those patients who did not respond. Our
      results suggest that Cdc6 is a potential prognostic marker and therapeutic target
      in breast cancer patients.

PMID- 28428558
TI  - A joint analysis of influenza-associated hospitalizations and mortality in Hong
      Kong, 1998-2013.
AB  - Influenza viruses may cause severe human infections leading to hospitalization or
      death. Linear regression models were fitted to population-based data on
      hospitalizations and deaths. Surveillance data on influenza virus activity
      permitted inference on influenza-associated hospitalizations and deaths. The
      ratios of these estimates were used as a potential indicator of severity.
      Influenza was associated with 431 (95% CrI: 358-503) respiratory deaths and
      12,700 (95% CrI: 11,700-13,700) respiratory hospitalizations per year. Majority
      of the excess deaths occurred in persons >=65 y of age. The ratios of deaths to
      hospitalizations in adults >=65 y were significantly higher for influenza A(H1N1)
      and A(H1N1)pdm09 compared to A(H3N2) and B. Substantial disease burden associated
      with influenza viruses were estimated in Hong Kong particularly among children
      and elderly in 1998-2013. Infections with influenza A(H1N1) was suggested to be
      more serious than A(H3N2) in older adults.

PMID- 28428559
TI  - Habitat Variability and Ethnic Diversity in Northern Tibetan Plateau.
AB  - There are 56 officially-recognized ethnic groups in China. However, the distinct
      geographic patterns of various ethnic groups in relation to the physical
      environment in China have rarely been investigated. Based on the geo-referenced
      physical environmental parameters of 455 Han, Tu, Hui, Salar, Mongolian, and
      Tibetan communities in Qinghai, we found that the communities could be
      statistically demarcated by temperature and aridity threshold according to their
      ethnicity, implying that the geographic distribution of each ethnic group is
      mediated by the physical environment. We also observed that the habitat of each
      ethnic group is ecologically compatible with current subsistence strategies.
      Tibetans settle in cold and humid high-altitude regions owing to the cultivation
      of highland barley and the breeding of yak, dzo, Tibetan sheep and Tibetan goat.
      Mongolians survive by animal husbandry in cold and dry grassland areas. Han and
      Tu people settle in the Huangshui River Valley, which offers relatively humid
      climate and flat land for agriculture. Hui and Salar people occupy the Yellow
      River Valley with its relatively arid environment and grassland vegetation
      suitable for animal breeding. Our findings offer a new perspective in explaining
      the geographic patterns and the varieties of ethnic groups in China and
      elsewhere.

PMID- 28428560
TI  - Combination of High-density Microelectrode Array and Patch Clamp Recordings to
      Enable Studies of Multisynaptic Integration.
AB  - We present a novel, all-electric approach to record and to precisely control the
      activity of tens of individual presynaptic neurons. The method allows for
      parallel mapping of the efficacy of multiple synapses and of the resulting
      dynamics of postsynaptic neurons in a cortical culture. For the measurements, we
      combine an extracellular high-density microelectrode array, featuring 11'000
      electrodes for extracellular recording and stimulation, with intracellular patch
      clamp recording. We are able to identify the contributions of individual
      presynaptic neurons - including inhibitory and excitatory synaptic inputs - to
      postsynaptic potentials, which enables us to study dendritic integration. Since
      the electrical stimuli can be controlled at microsecond resolution, our method
      enables to evoke action potentials at tens of presynaptic cells in precisely
      orchestrated sequences of high reliability and minimum jitter. We demonstrate the
      potential of this method by evoking short- and long-term synaptic plasticity
      through manipulation of multiple synaptic inputs to a specific neuron.

PMID- 28428561
TI  - A general framework for predicting delayed responses of ecological communities to
      habitat loss.
AB  - Although biodiversity crisis at different spatial scales has been well
      recognised, the phenomena of extinction debt and immigration credit at a crossing
      scale context are, at best, unclear. Based on two community patterns, regional
      species abundance distribution (SAD) and spatial abundance distribution (SAAD),
      Kitzes and Harte (2015) presented a macroecological framework for predicting post
      disturbance delayed extinction patterns in the entire ecological community. In
      this study, we further expand this basic framework to predict diverse time-lagged
      effects of habitat destruction on local communities. Specifically, our
      generalisation of KH's model could address the questions that could not be
      answered previously: (1) How many species are subjected to delayed extinction in
      a local community when habitat is destructed in other areas? (2) How do rare or
      endemic species contribute to extinction debt or immigration credit of the local
      community? (3) How will species differ between two local areas? From the
      demonstrations using two SAD models (single-parameter lognormal and logseries),
      the predicted patterns of the debt, credit, and change in the fraction of unique
      species can vary, but with consistencies and depending on several factors. The
      general framework deepens the understanding of the theoretical effects of habitat
      loss on community dynamic patterns in local samples.

PMID- 28428562
TI  - Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance
      Anti-tumor Efficacy of Paclitaxel.
AB  - Paclitaxel (PTX), especially albumin-bound PTX in clinical, has displayed
      significant inhibition of tumor growth in patients. But the systemic distribution
      and poor water solubility of PTX often lead to severe side effects, consequently
      limiting the anti-tumor efficacy. In this study, we developed a novel PTX-loaded
      polymeric micelle drug delivery system. These self-assembled polymeric micelles
      from core to outside consisted of poly L-phenylalanine (pPhe), DTSSP linked poly
      L-lysine (pLys), poly ethylene glycol (PEG) and dehydroascorbic acids (DHA). pPhe
      formed the hydrophobic core to encapsulate PTX; DTSSPs on pLys covalently cross
      linked and formed disulfide bond to stabilize PTX from loss in blood circulation;
      PEG improved solubility to lower toxicity of PTX for its high hydrophilicity; DHA
      targeted tumors by specifically recognizing GLUT1 mainly expressed on tumor
      cells. Thus, PTX would be precisely released into tumor cells with high dose of
      glutathione to break disulfide bond. Moreover, these PTX-loaded polymer micelles
      significantly suppressed tumor cell viability, proliferation, and migration in
      vitro, and also greatly inhibited tumor growth and prolonged survival in tumor
      bearing mice without detectable side effects. Therefore, the new drug delivery
      system could reduce severe side effects and enhance anti-tumor efficacy of PTX
      via peripheral stabilization, low toxicity and tumor targeting.

PMID- 28428563
TI  - A sublethal dose of a neonicotinoid insecticide disrupts visual processing and
      collision avoidance behaviour in Locusta migratoria.
AB  - Neonicotinoids are known to affect insect navigation and vision, however the
      mechanisms of these effects are not fully understood. A visual motion sensitive
      neuron in the locust, the Descending Contralateral Movement Detector (DCMD),
      integrates visual information and is involved in eliciting escape behaviours. The
      DCMD receives coded input from the compound eyes and monosynaptically excites
      motorneurons involved in flight and jumping. We show that imidacloprid (IMD)
      impairs neural responses to visual stimuli at sublethal concentrations, and these
      effects are sustained two and twenty-four hours after treatment. Most
      significantly, IMD disrupted bursting, a coding property important for motion
      detection. Specifically, IMD reduced the DCMD peak firing rate within bursts at
      ecologically relevant doses of 10 ng/g (ng IMD per g locust body weight). Effects
      on DCMD firing translate to deficits in collision avoidance behaviours: exposure
      to 10 ng/g IMD attenuates escape manoeuvers while 100 ng/g IMD prevents the
      ability to fly and walk. We show that, at ecologically-relevant doses, IMD causes
      significant and lasting impairment of an important pathway involved with visual
      sensory coding and escape behaviours. These results show, for the first time,
      that a neonicotinoid pesticide directly impairs an important, taxonomically
      conserved, motion-sensitive visual network.

PMID- 28428564
TI  - Nanometre-scale 3D defects in Cr2AlC thin films.
AB  - MAX-phase Cr2AlC containing thin films were synthesized by magnetron sputtering
      in an industrial system. Nanometre-scale 3D defects are observed near the
      boundary between regions of Cr2AlC and of the disordered solid solution
      (CrAl)xCy. Shrinkage of the Cr-Cr interplanar distance and elongation of the Cr
      Al distance in the vicinity of the defects are detected using transmission
      electron microscopy. The here observed deformation surrounding the defects was
      described using density functional theory by comparing the DOS of bulk Cr2AlC
      with the DOS of a strained and unstrained Cr2AlC(0001) surface. From the partial
      density of states analysis, it can be learned that Cr-C bonds are stronger than
      Cr-Al bonds in bulk Cr2AlC. Upon Cr2AlC(0001) surface formation, both bonds are
      weakened. While the Cr-C bonds recover their bulk strength as Cr2AlC(0001) is
      strained, the Cr-Al bonds experience only a partial recovery, still being weaker
      than their bulk counterparts. Hence, the strain induced bond strengthening in
      Cr2AlC(0001) is larger for Cr d - C p bonds than for Cr d - Al p bonds. The here
      observed changes in bonding due to the formation of a strained surface are
      consistent with the experimentally observed elongation of the Cr-Al distance in
      the vicinity of nm-scale 3D defects in Cr2AlC thin films.

PMID- 28428567
TI  - Novel oral anticoagulants and exodontia: the evidence.
AB  - Background Haemostasis is crucial for the success of oral surgical treatment as
      bleeding problems can cause complications both pre- and post-operatively.
      Patients on anticoagulant drugs present a challenge due to their increased risk
      of bleeding.Aims To review the evidence for the management of oral surgery
      patients on novel oral anticoagulant therapy.Methods A literature review was
      conducted in May 2016 of free-text and MESH searches (keywords: apixaban,
      dabigatran, rivaroxaban and dental extractions) in the Cochrane Library, PubMed
      and CINAHL. Trial registers, professional bodies for guidelines and OpenGrey for
      unpublished literature were also searched. Studies were selected for appraisal
      after limits were applied (adult, human and English only studies) and
      inclusion/exclusion criteria imposed.Results Five studies were identified for
      critical appraisal using the CASP tools. These were a combination of systematic
      reviews and case series. Two case series were excluded due to low quality
      evidence. Curtin et al., Davis et al. and Constantinides et al. together with
      guidelines from the Scottish Dental Clinical Effectiveness Programme, have
      highlighted a protocol in managing these patients in a dental surgical
      setting.Conclusion Patients on novel anticoagulant therapy requiring dental
      surgery can be managed appropriately either without discontinuation of therapy or
      a delay in dose. For those patients at higher risks of postoperative bleeding
      complications, it is advised to liaise with the specialist physician.

PMID- 28428568
TI  - Pharmacology: Sea change of indications.

PMID- 28428565
TI  - Small methyltransferase RlmH assembles a composite active site to methylate a
      ribosomal pseudouridine.
AB  - Eubacterial ribosomal large-subunit methyltransferase H (RlmH) methylates 23S
      ribosomal RNA pseudouridine 1915 (Psi1915), which lies near the ribosomal
      decoding center. The smallest member of the SPOUT superfamily of
      methyltransferases, RlmH lacks the RNA recognition domain found in larger
      methyltransferases. The catalytic mechanism of RlmH enzyme is unknown. Here, we
      describe the structures of RlmH bound to S-adenosyl-methionine (SAM) and the
      methyltransferase inhibitor sinefungin. Our structural and biochemical studies
      reveal catalytically essential residues in the dimer-mediated asymmetrical active
      site. One monomer provides the SAM-binding site, whereas the conserved C-terminal
      tail of the second monomer provides residues essential for catalysis. Our
      findings elucidate the mechanism by which a small protein dimer assembles a
      functionally asymmetric architecture.

PMID- 28428570
TI  - Investigation of the erosive potential of sour novelty sweets.
AB  - Background The expansion of the novelty sweets market in the UK has major
      potential public health implications in children and young adults as they may
      cause dental erosion.Objective To investigate the erosive potential of the
      novelty sweets in term of their physiochemical properties and amount of enamel
      loss.Subjects and methods The pH of a variety of novelty sweets was tested in
      vitro using a pH meter and the neutralisable acidity was assessed by titrating
      the sweets against 0.1M NaOH. The viscosity of the novelty sweets was measured
      using a rotational viscometer. The wettability of enamel by each sweet was
      measured using dynamic contact angle analyser. Enamel loss was assessed using
      contact profilometry.Results The pH ranged from 1.8-3.2, the neutralisable
      acidity ranged from 9-201 ml of 0.1 NaOH. The viscosity of the novelty sweets
      that come in liquid form ranged from 2-594 mPa s. The surface enamel erosion
      ranged from 1.95-15.77 MUm and from 2.5-17.6 MUm with and without immersing in
      saliva for 1 hour before immersing in acidic solution respectively. The amount of
      subsurface enamel loss was ranged from 0.75 to 2.3 MUm following ultrasonication
      at 0 min of acidic attack and from 0.23 to 0.85 MUm at 60 minutes of acidic
      attack while immersed in saliva. The contact angle between enamel surface and
      four sweet was less than the angle formed between the orange juice and the enamel
      which caused more wettability of enamel.Conclusion The pH is lower than the
      critical value for enamel erosion (5.5), high neutralisable acidity and high
      sugar content strongly suggest that these sweets may cause significant amount of
      dental erosion clinically. In addition, the degree of wettability of enamel by
      solution is an important factor to consider in determining the enamel loss caused
      by acidic solution. Immediate tooth brushing would cause further enamel loss as a
      result of the mechanical removal of softened enamel. However, it has been
      suggested that postponing brushing after erosive attack should be reconsidered.

PMID- 28428573
TI  - Fitness to practise: A question of reputation.

PMID- 28428574
TI  - The oral health of individuals with dental phobia: a multivariate analysis of the
      Adult Dental Health Survey, 2009.
AB  - Background Adults with dental phobia have been reported to have poorer oral
      health and oral health-related quality of life. The aim of this study is to
      explore the social and demographic correlates of oral health and oral health
      related quality of life (OH-QoL) of people with dental phobia compared to the non
      phobic population in the United Kingdom using the data from Adult Dental Health
      Survey (ADHS, 2009).Method Secondary analysis of data from the ADHS, 2009. A
      series of logistic regression analyses was performed with outcome measures of:
      presence of decayed teeth; presence of missing teeth; pulp exposure ulceration
      fistula abscess (PUFA) score; periodontal health indices (plaque, bleeding and
      loss of attachments); and quality of life (oral health impact profile [OHIP14]
      and oral impacts on daily performance [OIDP]). Predictors included in the models
      were: the presence of dental phobia; age; gender; occupational status; oral
      health-related behaviour; dietary intake of sugars; and perception of their last
      visit.Results People with dental phobia are more likely to have one or more
      decayed (caries) teeth/missing teeth. Furthermore, their self-reported oral
      health-related quality of life (OH-QoL) is poorer. There were no differences in
      PUFA scores or periodontal disease.Conclusion The impact of dental phobia on oral
      health appears to operate largely through the increased likelihood of the
      presence of caries, since there is an increased likelihood of the presence of
      teeth with active caries and missing teeth when other predictors of disease
      experience are controlled in the analysis.

PMID- 28428575
TI  - Emotional relationships between child patients and their mothers during dental
      treatments.
AB  - But did the 'uncooperative child' demonstrate higher sympathetic nervous activity
      because they were bound in the restraining device?

PMID- 28428576
TI  - Crispian Scully.

PMID- 28428578
TI  - Professionalism in spite of it all.

PMID- 28428581
TI  - Charles Tomes lecture addresses the 'trauma of trauma'.

PMID- 28428580
TI  - A review of mouthguards: effectiveness, types, characteristics and indications
      for use.
AB  - Participation in sport carries an increased risk of sustaining dental trauma
      which can be reduced by the use of a mouthguard. Mouthguards work by dissipating
      the force of impact, thus reducing the force which is transferred to the
      dentition. There are different types of mouthguard available which vary in
      design, costs and the level of protection provided. This article aims to review
      the use of mouthguards in sport, the common barriers to their use and also the
      different types of mouthguards and their characteristics.

PMID- 28428582
TI  - Dental research: Collaboration needed.

PMID- 28428585
TI  - OMFS: GA rights.

PMID- 28428586
TI  - A dentist's life: Helping dentists prevent poor posture and back pain.

PMID- 28428588
TI  - Effect of hypnosis during administration of local anesthesia in six- to 16-year
      old children.
AB  - Hypnosis improved the acceptance of local anaesthetic in children.

PMID- 28428590
TI  - Dental patients: Self-diagnosis.

PMID- 28428592
TI  - Antibiotic prophylaxis for infective endocarditis: some rarely addressed issues.
AB  - Although quite consistent indications on antibiotic prophylaxis for infective
      endocarditis (IE) have been reported internationally, several common dental
      practice issues are still not clear: which dental procedures require antibiotic
      prophylaxis? In the case of multiple procedures can the same antibiotic be used?
      How can dentists identify high-risk conditions for IE? Do dentists verify patient
      antibiotic intake? What are the requirements of antibiotic prophylaxis in cases
      of coexistence of diseases which involve host defence impairment? What are the
      modalities of second choice drug administration? And finally, are chlorhexidine
      mouthwashes before dental procedures combined with antibiotics useful or not?
      Uncertainty also persists as far as the real need for prophylaxis is concerned
      and although several sources have suggested that a wide prospective randomised
      controlled study may be the definitive solution, problems exist in performing
      such a study.

PMID- 28428594
TI  - Endorsed effectiveness.

PMID- 28428597
TI  - Outcomes and costs of pre-school and school-based fluoride varnish pilots.
AB  - Objective Fluoride varnish (FV) applications reduce the risk of dental decay in
      research trials. These pilots were conducted to test the feasibility and costs of
      providing FV applications in schools. Changes in dental decay levels were also
      monitored.Methods Data were collected on the proportion of children with dental
      decay, mean number of teeth affected and whether the child had attended for
      dental care. The cost of delivering the intervention was calculated.Results More
      children were reported to be attending for dental care by the end of the pilot
      than at the start. The proportion of children with dental decay and the mean
      number of teeth affected increased, but more children seemed to have received
      treatment. The intervention cost about L88 per child per year, with most of the
      costs due to the intensive efforts needed to recruit and maintain participation
      in the pilots.Conclusions Establishing community FV programmes requires
      significant investment and the long-term benefits in practice are unclear. If
      dental decay levels are to be reduced, there is a need to improve diets,
      alongside fluoride strategies. This may be best achieved by integrating oral
      health improvement programmes into other health programmes, particularly sugar
      reduction strategies.

PMID- 28428598
TI  - Non-surgical management of tooth hypersensitivity.
AB  - It would appear that toothpastes containing arginine and calcium carbonate (for
      example Colgate(r) Sensitive Pro-ReliefTM) are particularly effective at managing
      tooth sensitivity.

PMID- 28428599
TI  - BDJ and MI at Conference.

PMID- 28428602
TI  - British Dental Association (the 'company') (registered in england and wales with
      company number 14161) Annual General Meeting.

PMID- 28428600
TI  - Water fluoridation: There is no evidence.

PMID- 28428604
TI  - In vitro cavity and crown preparations and direct restorations: A comparison of
      performance at the start and end of the FD programme.
AB  - Aim To assess the performance and thereby the progress of the FDs when they
      carried out a number of simulated clinical exercises at the start and at the end
      of their FD year.Methods A standardised simulated clinical restorative dentistry
      training exercise was carried out by a group of 61 recently qualified dental
      graduates undertaking a 12 months' duration foundation training programme in
      England, at both the start and end of the programme. Participants completed a
      Class II cavity preparation and amalgam restoration, a Class IV composite resin
      restoration and two preparations for a porcelain-metal full crown. The completed
      preparations and restorations were independently assessed by an experienced
      consultant in restorative dentistry, using a scoring system based on previously
      validated criteria. The data were subjected to statistical analysis.Results There
      was wide variation in individual performance. Overall, there was a small but not
      statistically significant improvement in performance by the end of the programme.
      A statistically significant improvement was observed for the amalgam preparation
      and restoration, and, overall, for one of the five geographical sub-groups in the
      study. Possible reasons for the variable performance and improvement are
      discussed.Conclusions There was variability in the performance of the FDs. The
      operative performance of FDs at the commencement and end of their FD year
      indicated an overall moderately improved performance over the year and a
      statistically significant improvement in their performance with regard to amalgam
      restoration.

PMID- 28428605
TI  - Orthodontics: Link with obesity.

PMID- 28428608
TI  - Futuristic virtual reality training unveiled.

PMID- 28428609
TI  - Socket preservation.
AB  - Socket preservation maintains bone volume post-extraction in anticipation of an
      implant placement or fixed partial denture pontic site. This procedure helps
      compensate for the resorption of the facial bone wall. Socket preservation should
      be considered when implant placement needs to be delayed for patient or site
      related reasons. The ideal healing time before implant placement is six months.
      Socket preservation can reduce the need for later bone augmentation. By reducing
      bone resorption and accelerating bone formation it increases implant success and
      survival. Biomaterials for socket grafting including autograft, allograft,
      xenograft and alloplast. A bone substitute with a low substitution rate is
      recommended.

PMID- 28428610
TI  - Joy Harrild Award for Young Dentists launched.

PMID- 28428611
TI  - Transcription Factor Antagonism Controls Enteroendocrine Cell Specification from
      Intestinal Stem Cells.
AB  - The balanced maintenance and differentiation of local stem cells is required for
      Homeostatic renewal of tissues. In the Drosophila midgut, the transcription
      factor Escargot (Esg) maintains undifferentiated states in intestinal stem cells,
      whereas the transcription factors Scute (Sc) and Prospero (Pros) promote
      enteroendocrine cell specification. However, the mechanism through which Esg and
      Sc/Pros coordinately regulate stem cell differentiation is unknown. Here, by
      combining chromatin immunoprecipitation analysis with genetic studies, we show
      that both Esg and Sc bind to a common promoter region of pros. Moreover,
      antagonistic activity between Esg and Sc controls the expression status of Pros
      in stem cells, thereby, specifying whether stem cells remain undifferentiated or
      commit to enteroendocrine cell differentiation. Our study therefore reveals
      transcription factor antagonism between Esg and Sc as a novel mechanism that
      underlies fate specification from intestinal stem cells in Drosophila.

PMID- 28428612
TI  - Granzyme K-deficient mice show no evidence of impaired antiviral immunity.
AB  - The biological role of granzyme K, a serine protease of cytotoxic T lymphocytes
      (CTL), is controversial. It has been reported to induce perforin-mediated cell
      death in vitro, but is also reported to be non-cytotoxic and to operate in
      inflammatory processes. To elucidate the biological role of this protease, we
      have deleted the granzyme K gene in mice (mutant allele: Gzmktm1.1Pib;
      MGI:5636646). Gzmk -/- mice are healthy, anatomically normal, fecund and show
      normal hematopoietic development. Gzmk -/- mice readily recover from lymphocytic
      choriomeningitis virus and mouse pox Ectromelia virus infection. Ex vivo, virus
      specific granzyme K-deficient CTL are indistinguishable from those of wild-type
      mice in apoptosis induction of target cells. These data suggest that granzyme K
      does not play an essential role in viral immunity or cytotoxicity. Our granzyme K
      knockout line completes the collection of mouse models for the human granzymes,
      and will further our understanding of their biological roles and relationships.

PMID- 28428614
TI  - Homer1b/c clustering is impaired in Phelan-McDermid Syndrome iPSCs derived
      neurons.

PMID- 28428613
TI  - Differential regulation of PKD isoforms in oxidative stress conditions through
      phosphorylation of a conserved Tyr in the P+1 loop.
AB  - Protein kinases are essential molecules in life and their crucial function
      requires tight regulation. Many kinases are regulated via phosphorylation within
      their activation loop. This loop is embedded in the activation segment, which
      additionally contains the Mg2+ binding loop and a P + 1 loop that is important in
      substrate binding. In this report, we identify Abl-mediated phosphorylation of a
      highly conserved Tyr residue in the P + 1 loop of protein kinase D2 (PKD2) during
      oxidative stress. Remarkably, we observed that the three human PKD isoforms
      display very different degrees of P + 1 loop Tyr phosphorylation and we identify
      one of the molecular determinants for this divergence. This is paralleled by a
      different activation mechanism of PKD1 and PKD2 during oxidative stress. Tyr
      phosphorylation in the P + 1 loop of PKD2 increases turnover for Syntide-2, while
      substrate specificity and the role of PKD2 in NF-kappaB signaling remain
      unaffected. Importantly, Tyr to Phe substitution renders the kinase inactive,
      jeopardizing its use as a non-phosphorylatable mutant. Since large-scale
      proteomics studies identified P + 1 loop Tyr phosphorylation in more than 70
      Ser/Thr kinases in multiple conditions, our results do not only demonstrate
      differential regulation/function of PKD isoforms under oxidative stress, but also
      have implications for kinase regulation in general.

PMID- 28428615
TI  - Metabolic Disease: Protein tyrosine phosphatase inhibitor reverses diabetes.

PMID- 28428616
TI  - Cancer: Belt and braces for BCR-ABL.

PMID- 28428617
TI  - Deterministic Spin-Orbit Torque Induced Magnetization Reversal In Pt/[Co/Ni] n
      /Co/Ta Multilayer Hall Bars.
AB  - Spin-orbit torque (SOT) induced by electric current has attracted extensive
      attention as an efficient method of controlling the magnetization in nanomagnetic
      structures. SOT-induced magnetization reversal is usually achieved with the aid
      of an in-plane bias magnetic field. In this paper, we show that by selecting a
      film stack with weak out-of-plane magnetic anisotropy, field-free SOT-induced
      switching can be achieved in micron sized multilayers. Using direct current,
      deterministic bipolar magnetization reversal is obtained in Pt/[Co/Ni]2/Co/Ta
      structures. Kerr imaging reveals that the SOT-induced magnetization switching
      process is completed via the nucleation of reverse domain and propagation of
      domain wall in the system.

PMID- 28428618
TI  - Pulmonary delivery of triptolide-loaded liposomes decorated with anti-carbonic
      anhydrase IX antibody for lung cancer therapy.
AB  - Antibody-decorated liposomes can facilitate the precise delivery of
      chemotherapeutic drugs to the lung by targeting a recognition factor present on
      the surface of lung tumor cells. Carbonic anhydrase IX (CA IX) is an enzyme
      expressed on the surface of lung cancer cells with a restricted expression in
      normal lungs. Here, we explored the utility of anti-carbonic anhydrase IX (CA IX)
      antibody, conjugated to the surface of triptolide (TPL)-loaded liposomes (CA IX
      TPL-Lips), to promote the therapeutic effects for lung cancer via pulmonary
      administration. It was found that the CA IX-TPL-Lips significantly improved the
      cellular uptake efficiency in both CA IX-positive human non-small cell lung
      cancer cells (A549) and A549 tumor spheroids, resulting in the efficient cell
      killing compared with free TPL and non-targeted TPL-Lips. In vivo, CA IX-Lips via
      pulmonary delivery showed specificity and a sustained release property resided up
      to 96 h in the lung, both of which improved the efficiency of TPL formulations in
      restraining tumor growth and significantly prolonged the lifespan of mice with
      orthotopic lung tumors. The results suggest that CA IX-decorated liposomes can
      potentially be used as an effective therapeutic strategy for lung cancer.

PMID- 28428619
TI  - Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in
      rVSV-EBOV mediated protection.
AB  - Ebola virus (EBOV) poses a significant threat to human health as highlighted by
      the recent epidemic in West Africa. Data from animal studies and a ring
      vaccination clinical trial conducted in Guinea during the recent epidemic
      demonstrated that a recombinant VSV where G protein is replaced with EBOV GP
      (rVSV-EBOV) is safe and highly efficacious. We previously established that
      antibodies are essential for rVSV-EBOV mediated protection against EBOV; however,
      the mechanisms by which this vaccine induces a humoral response and the role of T
      cells in rVSV-EBOV mediated protection remain poorly understood. Since this is
      the only vaccine platform that has completed Phase III clinical studies, it is
      imperative to gain a better understanding of its mechanisms of protection.
      Therefore, we performed a longitudinal gene expression analysis of samples
      collected from controls and T-cell-depleted macaques after rVSV-EBOV vaccination
      and EBOV challenge. We show that rVSV-EBOV vaccination induces gene expression
      changes consistent with anti-viral immunity and B-cell proliferation. We also
      report a previously unappreciated role for CD8+ T-cells in mediating rVSV-EBOV
      protection. Finally, limited viral transcription in surviving animals may boost
      protective responses after EBOV challenge by maintaining transcriptional changes.
      This study presents a novel approach in determining mechanisms of vaccine
      efficacy.

PMID- 28428621
TI  - Osteoarthritis: Metabolic syndrome and risk of knee OA.

PMID- 28428620
TI  - Formal Definitions of Unbounded Evolution and Innovation Reveal Universal
      Mechanisms for Open-Ended Evolution in Dynamical Systems.
AB  - Open-ended evolution (OEE) is relevant to a variety of biological, artificial and
      technological systems, but has been challenging to reproduce in silico. Most
      theoretical efforts focus on key aspects of open-ended evolution as it appears in
      biology. We recast the problem as a more general one in dynamical systems theory,
      providing simple criteria for open-ended evolution based on two hallmark
      features: unbounded evolution and innovation. We define unbounded evolution as
      patterns that are non-repeating within the expected Poincare recurrence time of
      an isolated system, and innovation as trajectories not observed in isolated
      systems. As a case study, we implement novel variants of cellular automata (CA)
      where the update rules are allowed to vary with time in three alternative ways.
      Each is capable of generating conditions for open-ended evolution, but vary in
      their ability to do so. We find that state-dependent dynamics, regarded as a
      hallmark of life, statistically out-performs other candidate mechanisms, and is
      the only mechanism to produce open-ended evolution in a scalable manner,
      essential to the notion of ongoing evolution. This analysis suggests a new
      framework for unifying mechanisms for generating OEE with features distinctive to
      life and its artifacts, with broad applicability to biological and artificial
      systems.

PMID- 28428622
TI  - Inhibition of late sodium current suppresses calcium-related ventricular
      arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel
      expressions.
AB  - Cardiac arrhythmias associated with intracellular calcium inhomeostasis are
      refractory to antiarrhythmic therapy. We hypothesized that late sodium current (I
      Na) contributed to the calcium-related arrhythmias. Monophasic action potential
      duration at 90% completion of repolarization (MAPD90) was significantly increased
      and ventricular arrhythmias were observed in hearts with increased intracellular
      calcium concentration ([Ca2+]i) by using Bay K 8644, and the increase became
      greater in hearts treated with a combination of ATX-II and Bay K 8644 compared to
      Bay K 8644 alone. The prolongations caused by Bay K 8644 and frequent episodes of
      ventricular tachycardias, both in absence and presence of ATX-II, were
      significantly attenuated or abolished by late I Na inhibitors TTX and eleclazine.
      In rabbit ventricular myocytes, Bay K 8644 increased I CaL density, calcium
      transient and myocyte contraction. TTX and eleclazine decreased the amplitude of
      late I Na, the reverse use dependence of MAPD90 at slower heart rate, and
      attenuated the increase of intracellular calcium transient and myocyte
      contraction. TTX diminished the phosphorylation of CaMKII-delta and Nav 1.5 in
      hearts treated with Bay K 8644 and ATX-II. In conclusion, late I Na contributes
      to ventricular arrhythmias and its inhibition is plausible to treat arrhythmias
      in hearts with increased [Ca2+]i.

PMID- 28428623
TI  - Paper strip-embedded graphene quantum dots: a screening device with a smartphone
      readout.
AB  - Simple, inexpensive and rapid sensing systems are very demanded for a myriad of
      uses. Intrinsic properties of emerging paper-based analytical devices have
      demonstrated considerable potential to fulfill such demand. This work reports an
      easy-to-use, low cost, and disposable paper-based sensing device for rapid
      chemical screening with a smartphone readout. The device comprises luminescent
      graphene quantum dots (GQDs) sensing probes embedded into a nitrocellulose matrix
      where the resonance energy transfer phenomenon seems to be the sensing mechanism.
      The GQDs probes were synthesized from citric acid by a pyrolysis procedure,
      further physisorbed and confined into small wax-traced spots on the
      nitrocellulose substrate. The GQDs were excited by an UV LED, this, is powered by
      a smartphone used as both; energy source and imaging capture. The LED was
      contained within a 3D-printed dark chamber that isolates the paper platform from
      external light fluctuations leading to highly reproducible data. The cellulose
      based device was proven as a promising screening tool for phenols and polyphenols
      in environmental and food samples, respectively. It opens up new opportunities
      for simple and fast screening of organic compounds and offers numerous
      possibilities for versatile applications. It can be especially useful in remote
      settings where sophisticated instrumentation is not always available.

PMID- 28428625
TI  - Recovery of Alumina Nanocapacitors after High Voltage Breakdown.
AB  - Breakdown of a dielectric material at high electric fields significantly limits
      the applicability of metal-dielectric-metal capacitors for energy storage
      applications. Here we demonstrate that the insulating properties of atomic-layer
      deposited Al2O3 thin films in Al/Al2O3/Al trilayers can recover after the
      breakdown. The recovery has been observed in samples with the dielectric
      thickness spanning from 4 to 9 nm. This phenomenon holds promise for a new
      generation of capacitors capable of restoring their properties after the
      dielectric breakdown. Also, if employed in capacitor banks, the recovery process
      will ensure that the bank remains operational even if a breakdown occurs.

PMID- 28428624
TI  - Attentional selection predicts rapid automatized naming ability in Chinese
      speaking children with ADHD.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) are reported to
      have a significantly higher risk of showing reading difficulties or disorders.
      Here, we aimed to identify the relationship between electroencephalographic (EEG)
      marker of spatial attention and reading ability in Chinese children with ADHD.
      First, we demonstrated that rapid automatized naming (RAN) is a strong predictor
      of reading ability in Chinese-speaking children. Then, EEG data of 9-to 15-year
      old children with ADHD (n = 38) and typically developing (TD) controls (n = 36)
      were collected while the children performed a classical visual search task.
      Children with ADHD showed slower RAN speed than TD children. For event-related
      potentials (ERPs), children with ADHD showed a reduced target-evoked N2pc
      component, which predicted their poorer RAN performance. However, in TD children
      the early occipital P1 amplitude was negatively correlated with their RAN
      performance. The correlation between decreased N2pc and poor RAN performance in
      children with ADHD suggests that their reading problems may in part be due to
      impaired attentional selection. In contrast, in TD children, development in early
      visual processing co-occurs with improvements in reading ability.

PMID- 28428626
TI  - C1QBP suppresses cell adhesion and metastasis of renal carcinoma cells.
AB  - Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously
      expressed cellular protein and can be upregulated or activated in a variety of
      malignant tumors, including those from thyroid, colon and breast, but its role
      remains unclear in renal cell carcinoma (RCC). In this study, C1QBP knockdown in
      RCC cell influenced expression of multiple genes associated with cell adhesion,
      among which L1 cell adhesion molecule (L1CAM) was significantly higher upon a
      reduction of C1QBP. In turn, cell adhesion and invasion abilities were
      significantly increased with increased metastasis to lung and liver in vivo.
      C1QBP may regulate RCC cell adhesion and invasion through influencing the p
      GSK3/beta-Catenin/L1CAM expression. Over all, our study demonstrated that C1QBP
      could regulate RCC metastasis by regulating the GSK3/beta-Catenin/L1CAM signaling
      pathway.

PMID- 28428627
TI  - Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and
      Facilitate Mycobacterial Survival in Macrophages.
AB  - Chronic administration of glucocorticoids has been shown to render individuals
      highly susceptible to mycobacterial infection and lead to reactivation of latent
      bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial
      defense, especially in macrophages remains largely unknown. Here, we found that
      glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide
      production and autophagy in mycobacteria-challenged macrophages. Meanwhile,
      maturation and acidification of mycobacterial phagosomes were attenuated in
      RAW264.7 cells after glucocorticoids treatment. Consequently, we observed a
      glucocorticoid-induced increase in the survival of intracellular mycobacteria in
      both primary macrophages and cell lines. Glucocorticoids treatment decreased the
      activation of TBK1 kinase, which promotes the maturation of autophagosomes.
      Inhibition of TBK1 also decreased the production of nitric oxide. Furthermore,
      several autophagy-related genes were down-regulated, while activation of the
      Akt/mTOR signaling pathway was increased after glucocorticoids treatment, which
      may account for autophagy inhibition during mycobacterial infection. Restoration
      of autophagy with the agonist rapamycin abolished glucocorticoid-mediated
      enhancement of mycobacterial survival, suggesting that glucocorticoids blocked
      anti-mycobacterial defense via autophagy inhibition. Collectively, this study
      demonstrates that glucocorticoids impair innate antimicrobial autophagy and
      promote mycobacterial survival in macrophages, which is a novel mechanism for
      glucocorticoid-mediated immunosuppression. Our findings may provide important
      clues for tuberculosis prevention.

PMID- 28428628
TI  - Inflammatory and Neuropathic Nociception is Preserved in GPR55 Knockout Mice.
AB  - The G-protein coupled receptor GPR55 has been postulated to serve as a novel
      cannabinoid receptor. A previous report indicated that GPR55 knockout mice fail
      to develop mechanical hyperalgesia, suggesting a pro-nociceptive role for GPR55
      in the control of nociceptive responding. However, GPR55 knockout mice remain
      incompletely characterized in models of pathological pain. Here we provide a
      comprehensive assessment of responses of GPR55 knockout and wild-type mice to
      mechanical and thermal (heat, cold) stimulation in multiple, mechanistically
      distinct models of inflammatory and neuropathic pain. Inflammatory sensitization
      was produced by intraplantar administration of capsaicin, formalin or complete
      Freund's adjuvant. No differences in responding were detected between GPR55
      knockout and wild-type mice in any model of inflammatory nociception assessed.
      Neuropathic pain was induced by partial sciatic nerve ligation (which induces
      hypersensitivity to mechanical, cold and heat stimulation) or by treatment with
      the chemotherapeutic agent paclitaxel (which induces hypersensitivity to
      mechanical and cold stimulation only). No differences were observed between GPR55
      knockout and wild type mice in either development or maintenance of neuropathic
      nociception in either neuropathic pain model. In conclusion, genetic deletion of
      GPR55 did not alter the development of pathological pain in adult mice in any
      chronic pain model evaluated.

PMID- 28428629
TI  - The role of glutamine synthetase isozymes in enhancing nitrogen use efficiency of
      N-efficient winter wheat.
AB  - Glutamine synthetase (GS) isozymes play critical roles in nitrogen (N)
      metabolism. However, the exact relationship between GS and nitrogen use
      efficiency (NUE) remain unclear. We have selected and compared two wheat
      cultivars, YM49 and XN509, which were identified as the N-efficient and N
      inefficient genotypes, respectively. In this study, agronomical, morphological,
      physiological and biochemical approaches were performed. The results showed that
      TaGS1 was high expressed post-anthesis, and TaGS2 was highly expressed pre
      anthesis in N-efficient genotype compared to N-inefficient genotype. GS1 and GS2
      isozymes were also separated by native-PAGE and found that the spatial and
      temporal distribution of GS isozymes, their expression of gene and protein
      subunits in source-sink-flow organs during development periods triggered the pool
      strength and influenced the N flow. According to the physiological role of GS
      isozymes, we illustrated four metabolic regulation points, by which acting
      collaboratively in different organs, accelerating the transport of nutrients to
      the grain. It suggested that the regulation of GS isozymes may promote flow
      strength and enhance NUE by a complex C-N metabolic mechanism. The relative
      activity or amount of GS1 and GS2 isozymes could be a potential marker to predict
      and select wheat genotypes with enhanced NUE.

PMID- 28428630
TI  - Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis
      in rhesus monkeys.
AB  - Autoantibodies against ion channels are the cause of numerous neurologic
      autoimmune disorders. Frequently, such pathogenic autoantibodies have a
      restricted epitope-specificity. In such cases, competing antibody formats devoid
      of pathogenic effector functions (blocker antibodies) have the potential to treat
      disease by displacing autoantibodies from their target. Here, we have used a
      model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys
      (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG
      was induced by passive transfer of pathogenic acetylcholine receptor-specific
      monoclonal antibody IgG1-637. The effect of the blocker antibody (IgG4Deltahinge
      637, the hinge-deleted IgG4 version of IgG1-637) was assessed using decrement
      measurements and single-fiber electromyography. Three daily doses of 1.7 mg/kg
      IgG1-637 (cumulative dose 5 mg/kg) induced impairment of neuromuscular
      transmission, as demonstrated by significantly increased jitter, synaptic
      transmission failures (blockings) and a decrease in the amplitude of the compound
      muscle action potentials during repeated stimulations (decrement), without
      showing overt symptoms of muscle weakness. Treatment with three daily doses of 10
      mg/kg IgG4Deltahinge-637 significantly reduced the IgG1-637-induced increase in
      jitter, blockings and decrement. Together, these results represent proof-of
      principle data for therapy of acetylcholine receptor-myasthenia gravis with a
      monovalent antibody format that blocks binding of pathogenic autoantibodies.

PMID- 28428631
TI  - An overview of the synergy and crosstalk between pentraxins and
      collectins/ficolins: their functional relevance in complement activation.
AB  - The complement system is an innate immune defense machinery comprising components
      that deploy rapid immune responses and provide efficient protection against
      foreign invaders and unwanted host elements. The complement system is activated
      upon recognition of pathogenic microorganisms or altered self-cells by exclusive
      pattern recognition molecules (PRMs), such as collectins, ficolins and
      pentraxins. Recent accumulating evidence shows that the different classes of
      effector PRMs build up a co-operative network and exert synergistic effects on
      complement activation. In this review, we describe our updated view of the
      crosstalk between previously unlinked PRMs in complement activation and the
      potential pathogenic effects during infection and inflammation.

PMID- 28428632
TI  - Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like
      cells leads to bladder hyperactivity in mice.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed
      to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is
      known about their possible role in cystitis-associated bladder dysfunction. The
      present study aimed to determine the functional role of HCN channels in
      regulating bladder function under inflammatory conditions. Sixty female wild-type
      C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to
      experimental and control groups, respectively. Cyclophosphamide (CYP)-induced
      cystitis models were successfully established in these mice. CYP treatment
      significantly enhanced HCN channel protein expression and Ih density and
      significantly altered bladder HCN1 channel regulatory proteins. Carbachol (CCH)
      and forskolin (FSK) exerted significant effects on bladder ICC-LC [Ca2+]i in CYP
      treated wild-type (WT) mice, and HCN1 channel ablation significantly decreased
      the effects of CCH and FSK on bladder ICC-LC [Ca2+]i in both naive and CYP
      treated mice. CYP treatment significantly potentiated the spontaneous
      contractions and CCH (0.001-10 MUM)-induced phasic contractions of detrusor
      strips, and HCN1 channel deletion significantly abated such effects. Finally, we
      demonstrated that the development of CYP-induced bladder overactivity was
      reversed in HCN1-/- mice. Taken together, our results suggest that CYP-induced
      enhancements of HCN1 channel expression and function in bladder ICC-LCs are
      essential for cystitis-associated bladder hyperactivity development, indicating
      that the HCN1 channel may be a novel therapeutic target for managing bladder
      hyperactivity.

PMID- 28428633
TI  - Inhibition of glutathione metabolism attenuates esophageal cancer progression.
AB  - Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with regard to
      mortality and prognosis, and the 5-year survival rate for all patients diagnosed
      with ESCC remains poor. A better understanding of the biological mechanisms of
      ESCC tumorigenesis and progression is of great importance to improve treatment of
      this disease. In this study, we demonstrated that the glutathione metabolism
      pathway is highly enriched in ESCC cells compared with normal esophageal
      epithelial cells in an in vivo mouse model. In addition, treatment with L
      buthionine-sulfoximine (BSO) to deplete glutathione decreased the ESCC tumor
      burden in mice, thus demonstrating the critical role of glutathione metabolism in
      ESCC progression. BSO treatment also led to decreased cell proliferation and
      activation of cell apoptosis in ESCC. Finally, BSO treatment blocked NF-kB
      pathway activation in ESCC. Our study reveals a new pathway that regulates ESCC
      progression and suggests that inhibition of glutathione metabolism may be a
      potential strategy for ESCC treatment.

PMID- 28428635
TI  - Sepsis: Bile acids promote inflammation in cholestasis-associated sepsis.

PMID- 28428636
TI  - Stem cells: Two sides to cancer stem cells in colorectal cancer.

PMID- 28428637
TI  - Surgery: Metabolic surgery: the cutting edge of diabetes care.

PMID- 28428638
TI  - Dynamic Behaviors of Condensing Clusters Based on Rayleigh Scattering Experiment.
AB  - Condensation is a common physical process which widely exists in natural
      phenomena and thermal energy systems. In a condensation process, cluster is
      considered as the important bridge between vapor body and condensates. However,
      limited by the minimum imaging dimension of traditional measurements, early
      experimental studies about initial stages of condensation process are not
      sufficient. This paper provides a powerful optical platform for the study of
      dynamic clusters process. Based on the Rayleigh law, optical experiments were
      firstly introduced to investigate the clusters spatial distribution close to and
      far from condensation surface. The results show that clusters are mainly
      generated in the vicinity of the condensation surface within the thickness of 200
      MUm. When they move away from the condensation surface, clusters progressively
      vanish and they have a life cycle of a fraction of a millisecond. Though
      scattering intensity is proportional to the 6th power of cluster radius r and
      cluster number density N c theoretically, the scattering intensity does not
      increase sharply with the increase of subcooling degree from the experimental
      results, so we can infer that the cluster number density plays a dominate role in
      this process and the effect of cluster radius almost can be ignored.Zhong Lan and
      Di Wang contributed equally to this work.

PMID- 28428634
TI  - Lipid droplets and liver disease: from basic biology to clinical implications.
AB  - Lipid droplets are dynamic organelles that store neutral lipids during times of
      energy excess and serve as an energy reservoir during deprivation. Many prevalent
      metabolic diseases, such as the metabolic syndrome or obesity, often result in
      abnormal lipid accumulation in lipid droplets in the liver, also called hepatic
      steatosis. Obesity-related steatosis, or NAFLD in particular, is a major public
      health concern worldwide and is frequently associated with insulin resistance and
      type 2 diabetes mellitus. Here, we review the latest insights into the biology of
      lipid droplets and their role in maintaining lipid homeostasis in the liver. We
      also offer a perspective of liver diseases that feature lipid accumulation in
      these lipid storage organelles, which include NAFLD and viral hepatitis. Although
      clinical applications of this knowledge are just beginning, we highlight new
      opportunities for identifying molecular targets for treating hepatic steatosis
      and steatohepatitis.

PMID- 28428639
TI  - Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor
      GHS-R.
AB  - Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same
      preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated
      insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin's
      effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R),
      but the physiologically relevant receptor of obestatin remains debatable. Here we
      have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo,
      and tested whether obestatin regulates insulin secretion through GHS-R. We found
      that under hyperglycemic condition, obestatin augments GSIS in rat insulinoma
      cells (INS-1) and in pancreatic islets from ghrelin -/- mice. Surprisingly,
      obestatin-induced GSIS was absent in beta-cells in which GHS-R was suppressed.
      Obestatin-induced insulin secretion was abolished in the circulation of Ghsr -/-
      mice, and in pancreatic islets isolated from Ghsr -/- mice. We also found that
      obestatin-induced GSIS was attenuated in islets isolated from beta-cell-specific
      Ghsr knockout MIP-Cre/ERT;Ghsrf/f mice. Our data collectively demonstrate that
      obestatin is a potent insulin secretagogue under hyperglycemic condition, and
      obestatin's effect on insulin secretion is mediated by GHS-R in pancreatic beta
      cells. Our findings reveal an intriguing insight that obestatin and ghrelin have
      opposing effects on insulin secretion, and both are mediated through ghrelin
      receptor GHS-R.

PMID- 28428640
TI  - Transforming growth factor beta plays an important role in enhancing wound
      healing by topical application of Povidone-iodine.
AB  - Povidone-iodine (PVI) is principally used as an antimicrobial agent. It has been
      found that 0.5% PVI can attenuate congestion, edema and pain induced by pressure
      sores. Thus this study aimed to assess the effects of 0.5% PVI on acute skin
      wounds. Four full-thickness excisional wounds were generated on the dorsal skin
      of male Sprague-Dawley rats with a 10-mm sterile punch. Two wounds were left
      untreated and the other two were dressed with gauze with 0.5% PVI for 1 hour per
      day for the first 5 days after injury. 10-mm full-thickness excisional wounds
      were also generated on the dorsal skin of rats treated with 10 mg/kg SB431542 and
      all wounds were treated with 0.5% PVI for 5 days. PVI treatment enhanced wound
      healing via promotion of expression of alpha SMA and TGF beta, neovascularization
      and re-epithelialization. Interleukin 6 was reduced following PVI treatment.
      Inhibition of TGF beta abolished the effect of PVI treatment on wound closure.
      These data show that topical application of 0.5% PVI could promote acute skin
      wound healing though increased expression of TGF beta leading to enhanced
      formation of granulation tissue, even in the absence of obvious infection.

PMID- 28428641
TI  - ?

PMID- 28428642
TI  - [Technology and prevention in the era of mobile health: applications for cancer
      screening programs].
AB  - The Italian national health system provides screening to detect breast,
      colorecatal and cervical cancers, however, population adherence is not as high as
      expected. Smartphones and their applications (apps) could be used as a tool to
      communicate with the population and to help improve adherence. The aim of this
      study was to analyze the features and functions of smartphone applications aimed
      at secondary prevention of oncological diseases. In February 2016, we reviewed
      online app stores, using specific key-words, to search for available apps for
      cancer screening. We identified 32 apps meeting our inclusion criteria. The most
      frequent types of app are breast cancer (13/32) and cervical cancer (4/32)
      screening apps. We also found apps addressing secondary prevention of cancers for
      which screening is not provided to the Italian population (melanoma, prostate
      cancer and hepatocellular carcinoma). The most common features are: information
      providers (22/32), risk calculators (10/32), reminders for appointments and tests
      (7/32). Only one app has been validated for diagnostic accuracy or utility using
      established international certification (CE Marking). The results show a large
      potential for development and utilization of applications in secondary
      prevention. Despite their potential usefulness, there are also disadvantages such
      as language barriers (only 2 of 32 apps are in Italian), and the digital divide.
      Future efforts should focus on improving education regarding approaches to
      technologies, strengthen national and international regulations and monitoring
      inequalities in access to services.

PMID- 28428643
TI  - [MISSCARE Survey - Italian Version: findings from an Italian validation study].
AB  - BACKGROUND: The Missed Nursing Care (MNC) refers to nursing interventions that
      are not completed, partially completed, or postponed. Despite the relevance of
      MNC, no assessment tools are available in the Italian context, and no data
      regarding the occurrence of this phenomenon has been documented on a large scale
      to date. OBJECTIVES: The study aims were: (1) to validate the Italian version of
      the MISSCARE Survey tool; (2) to measure the prevalence of missed interventions
      and reasons for missed care as perceived by clinical nurses working in Italian
      health care settings. METHODS: After having conducted the forward and backward
      translation, pre-pilot and pilot phases were developed to ensure face and content
      validity as well as semantic and conceptual equivalence of the Italian version
      with the original version. The MISSCARE survey questionnaire was then distributed
      to 1,233 clinical nurses of whom 1,003 completed the questionnaire. Overall, 979
      questionnaires were analysed. The questionnaires were completed from January to
      March 2012, by nurses working in medical and surgical hospital departments in the
      Emilia Romagna region of Italy. Construct validity and internal consistency of
      the instrument were assessed. RESULTS: The face and content validity were
      ascertained by a group of experts. The instrument acceptability was good given
      that 79.4% of respondents replied to all items. Construct validity was
      investigated by an Exploratory Factor Analysis. Four factors explaining 64.18% of
      variance emerged: communication, lack of facilities/supplies, lack of staff, and
      unexpected events. Internal consistency, evaluated with Cronbach a, was 0.94. The
      nursing interventions omitted with greater frequency were, in order: ambulation
      (74.8%), passive mobilization (69.6%) and oral care (51.3%). The three main
      reasons for missed interventions were: an unexpected increase in the number of
      patients (90.5%), increased instability of the clinical condition (86.1%) and
      insufficient human resources (85.5%). CONCLUSIONS: The Italian version of the
      MISSCARE Survey was shown to have good psychometric properties. Therefore, it can
      be used to evaluate the missed nursing care phenomenon in Italy and will allow
      for international comparisons.

PMID- 28428644
TI  - [How to evaluate the application of Clinical Governance tools in the management
      of hospitalized hyperglycemic patients: results of a multicentric study].
AB  - Risk management is a key tool in Clinical Governance. Our project aimed to
      define, share, apply and measure the impact of tools and methodologies for the
      continuous improvement of quality of care, especially in relation to the multi
      disciplinary and integrated management of the hyperglycemic patient in hospital
      settings. A training project, coordinated by a scientific board of experts in
      diabetes and health management and an Expert Meeting with representatives of all
      the participating centers was launched in 2014. The project involved eight
      hospitals through the organization of meetings with five managers and 25
      speakers, including diabetologists, internists, pharmacists and nurses. The
      analysis showed a wide variability in the adoption of tools and processes towards
      a comprehensive and coordinated management of hyperglycemic patients.

PMID- 28428645
TI  - Effect of tailored educational intervention to improve self-care maintenance and
      quality of life in postmenopausal osteoporotic women after a fragility fracture:
      the Guardian Angel&reg; study.
AB  - Osteoporosis has a significant impact on affected patients. Healthcare providers
      should encourage postmenopausal women to improve self-care maintenance behaviors
      and quality of life following a fragility fracture. The aims of this study were
      to a) develop two new instruments for measuring, respectively, self-care
      maintenance and quality of life, in postmenopausal women with osteoporosis; b)
      evaluate the effectiveness of a tailored educational intervention to improve self
      care maintenance and quality of life after a fragility fracture in postmenopausal
      women. For the first aim, a cross-sectional study will be performed; for the
      second aim, a multicenter, quasi-experimental, interventional design will be
      used. A convenience sample of postmenopausal women admitted to 44 hospitals in
      Italy with a diagnosis of bone fragility fracture will be enrolled and surveyed
      at 7, 30, 60 and 180 days after discharge. Trained nurses will conduct the
      educational intervention. The new instruments will allow the measurement of self
      care and quality of life in postmenopausal women following a fragility fracture.
      Through tailored educational interventions, women can be helped to take their
      medications correctly, adopt a healthy lifestyle, reduce the occurrence of bone
      fractures, and have a better quality of life.

PMID- 28428646
TI  - [HPV vaccination: active offer in an Italian region].
AB  - Human Papillomavirus is responsible for 4.8% of cancers, and is the main cause of
      cervical cancer. Cervical cancer can be reduced by mean of secondary prevention
      (PAP-test, HPV-DNA test), while through primary prevention (anti-HPV vaccine) the
      incidence of other HPV-attributable cancers can also be reduced. In Italy, anti
      HPV vaccination is part of the immunization schedule in girls since 2008, and in
      2017 it was extended to boys. However, vaccine coverage is decreasing nationwide.
      This study aims to examine anti-HPV vaccination practices in Health care services
      of Lazio Region, Italy. Questionnaires were sent or administered directly to
      those in charge of vaccinations. Data, collected from 11/12 (92%) Lazio Local
      Health Units and from 116 vaccination centers, show a remarkable diversity in the
      offer: 41% of the centers open only 1-2 days/week, 42% only in the morning, and
      only 7% are open on Saturday. Vaccination is available by reservation only in 62%
      of the centers, while vaccines are not administered to >=18 years subjects in
      33%; 93% of the centers call actively the girls in the target cohort, while 70%
      and 94% recall the patients who had not received the first or the second dose of
      vaccine, respectively. Collaboration with family physicians and/or pediatricians
      was declared by 80% of the centers. Vaccine coverage could probably be improved
      by addressing the highlighted critical issues and applying best practices widely.

PMID- 28428647
TI  - A PARTIALLY LINEAR FRAMEWORK FOR MASSIVE HETEROGENEOUS DATA.
AB  - We consider a partially linear framework for modelling massive heterogeneous
      data. The major goal is to extract common features across all sub-populations
      while exploring heterogeneity of each sub-population. In particular, we propose
      an aggregation type estimator for the commonality parameter that possesses the
      (non-asymptotic) minimax optimal bound and asymptotic distribution as if there
      were no heterogeneity. This oracular result holds when the number of sub
      populations does not grow too fast. A plug-in estimator for the heterogeneity
      parameter is further constructed, and shown to possess the asymptotic
      distribution as if the commonality information were available. We also test the
      heterogeneity among a large number of sub-populations. All the above results
      require to regularize each sub-estimation as though it had the entire sample
      size. Our general theory applies to the divide-and-conquer approach that is often
      used to deal with massive homogeneous data. A technical by-product of this paper
      is the statistical inferences for the general kernel ridge regression. Thorough
      numerical results are also provided to back up our theory.

PMID- 28428648
TI  - Ultrasound of ankles in the diagnosis of complications of chikungunya fever.
AB  - OBJECTIVE: To describe the main ultrasound findings of chikungunya fever in the
      ankle. MATERIALS AND METHODS: This was a cross-sectional observational study
      involving 52 patients referred to the Hospital Universitario Pedro Ernesto and
      presenting with clinical and biochemical evidence of chikungunya fever. The
      examinations were performed by a radiologist with more than 20 years of
      experience in ultrasound. RESULTS: The predominant gender was female (in 88.5%),
      and the mean age was 58.4 years. The majority (61.5%) of the patients came from
      the northern part of the city of Rio de Janeiro, and 46.2% were using
      corticosteroids to treat inflammatory symptoms. The most common alterations
      observed by ultrasound were joint effusion (in 69.2%), tenosynovitis (in 59.6%),
      cellulitis (in 46.2%), Kager's fat pad thickening (in 29.9%), myositis (of the
      soleus or flexor hallucis longus muscle) (in 17.3%), retrocalcaneal bursitis (in
      5.8%), tendon ruptures (in 3.8%), and increased vascular flow on power Doppler
      (in 3.8%). CONCLUSION: Signs of synovitis and tenosynovitis were the main
      ultrasound findings in a predominantly female population with a mean age of 58.4
      years. Further studies are needed in order to define the role of ultrasound in
      the follow-up of such patients.

PMID- 28428649
TI  - Role of magnetic resonance imaging in the planning of breast cancer treatment
      strategies: comparison with conventional imaging techniques.
AB  - OBJECTIVE: To assess the role of magnetic resonance imaging (MRI) in the planning
      of breast cancer treatment strategies. MATERIALS AND METHODS: The study included
      160 women diagnosed with breast cancer, who underwent breast MRI for preoperative
      staging. Using Pearson's correlation coefficient (r), we compared the size of the
      primary tumor, as determined by MRI, by conventional imaging (mammography and
      ultrasound), and in the pathological examination (gold standard). The
      identification of lesions not identified in previous examinations was also
      evaluated, as was its influence on treatment planning. RESULTS: The mean age of
      the patients was 52.2 years (range, 30-81 years), and the most common
      histological type was invasive ductal carcinoma (in 60.6% of the patients). In
      terms of the tumor size determined, MRI correlated better with the pathological
      examination than did mammography (r = 0.872 vs. 0.710) or ultrasound (r = 0.836
      vs. 0.704). MRI identified additional lesions in 53 patients (33.1%), including
      malignant lesions in 20 (12.5%), which led to change in the therapeutic planning
      in 23 patients (14.4%). CONCLUSION: Breast MRI proved to be more accurate than
      conventional imaging in determining the dimensions of the main tumor and was able
      to identify lesions not identified by other methods evaluated, which altered the
      therapeutic planning in a significant proportion of cases.

PMID- 28428650
TI  - Routine mammography: an opportunity for the diagnosis of chronic degenerative
      diseases? A cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to evaluate breast arterial calcification
      (BAC) detected on routine mammography, analyzing its association with chronic
      degenerative disease. MATERIALS AND METHODS: This was a cross-sectional study
      involving women treated at a specialized outpatient clinic for high-risk
      hypertension, diabetes, or chronic kidney disease, as well as volunteers who
      participated in a study to validate a method of screening for occult renal
      disease. A total of 312 patients between 40 and 69 years of age, with no history
      of breast cancer, all of whom had undergone routine mammography in the last two
      years, were included. The mammograms were analyzed by researchers who were
      unaware of the risk factors for BAC in each case. RESULTS: The mean age was 55.9
      +/- 7.4 years, and 64.3% of the patients were white. The mean glomerular
      filtration rate was 41.87 +/- 6.23 mL/min/1.73 m2. Seventy-one patients (22.8%)
      had BAC. We found that BAC was associated with advanced age, hypertension,
      diabetes, chronic kidney disease, and low glomerular filtration rate. In the
      multivariate analysis, advanced age and diabetes continued to be associated with
      BAC. The odds ratio for BAC was higher for all chronic diseases. CONCLUSION: The
      association of BAC with advanced age, hypertension, diabetes, chronic kidney
      disease, and low glomerular filtration rate should call the attention of
      radiologists. Therefore, the presence of BAC should be reported, and patients
      with BAC should be screened for those diseases.

PMID- 28428651
TI  - Utility of the inspiratory phase in high-resolution computed tomography
      evaluations of pediatric patients with bronchiolitis obliterans after allogeneic
      bone marrow transplant: reducing patient radiation exposure.
AB  - OBJECTIVE: To evaluate the utility of the inspiratory phase in high-resolution
      computed tomography (HRCT) of the chest for the diagnosis of post-bone marrow
      transplantation bronchiolitis obliterans. MATERIALS AND METHODS: This was a
      retrospective, observational, cross-sectional study. We selected patients of
      either gender who underwent bone marrow transplantation and chest HRCT between
      March 1, 2002 and December 12, 2014. Ages ranged from 3 months to 20.7 years. We
      included all examinations in which the HRCT was performed appropriately. The
      examinations were read by two radiologists, one with extensive experience in
      pediatric radiology and another in the third year of residency, who determined
      the presence or absence of the following imaging features: air trapping,
      bronchiectasis, alveolar opacities, nodules, and atelectasis. RESULTS: A total of
      222 examinations were evaluated (mean, 5.4 +/- 4.5 examinations per patient). The
      expiratory phase findings were comparable to those obtained in the inspiratory
      phase, except in one patient, in whom a small uncharacteristic nodule was
      identified only in the inspiratory phase. Air trapping was identified in a larger
      number of scans in the expiratory phase than in the inspiratory phase, as was
      atelectasis, although the difference was statistically significant only for air
      trapping. CONCLUSION: In children being evaluated for post-bone marrow
      transplantation bronchiolitis obliterans, the inspiratory phase can be excluded
      from the chest HRCT protocol, thus reducing by half the radiation exposure in
      this population.

PMID- 28428652
TI  - Percutaneous stent placement for the treatment of malignant biliary obstruction:
      nitinol versus elgiloy stents.
AB  - OBJECTIVE: This study aimed to compare two self-expanding stents, a nitinol stent
      and an elgiloy stent, both placed percutaneously, in terms of their efficacy in
      palliating inoperable malignant biliary obstruction. MATERIALS AND METHODS: We
      retrospectively investigated 99 patients with unresectable malignant biliary
      obstruction treated with percutaneous placement of a self-expanding metallic
      stent at our institution between May 2007 and January 2010. Serum bilirubin and
      liver enzyme levels were measured before and 30 days after stenting. For all
      procedures using elgiloy or nitinol stents, stent occlusion and patient survival
      rates were calculated using Kaplan-Meyer analysis. RESULTS: All of the patients
      showed clinical improvement after stent placement, with no difference between the
      two groups. In both groups, the occlusion-free survival rate was 67% at 30 days,
      37% at 90 days, 25% at 180 days, and 10% at 360 days, with no significant
      difference in relation to the type of stent. CONCLUSION: The two stents evaluated
      showed comparable efficacy for the percutaneous treatment of unresectable biliary
      malignancy, with good clinical results.

PMID- 28428653
TI  - Doppler velocimetry of the orbital arteries in patients with sickle cell anemia:
      relationship with biomarkers of hemolysis.
AB  - OBJECTIVE: To investigate orbital vascular resistance by Doppler velocimetry in
      patients with steady-state sickle cell anemia, as well as to characterize its
      relationship with biomarkers of hemolysis. MATERIALS AND METHODS: This was a
      cross-sectional study of two groups: 71 outpatients with sickle cell anemia; and
      32 age- and gendermatched, healthy subjects (control group). All participants
      underwent Doppler velocimetry of the orbital arteries and laboratory tests.
      RESULTS: All biochemical laboratory markers were abnormal in the sickle cell
      anemia patients (p < 0.0001 vs. controls). In the patient group, Doppler
      velocimetry revealed increased flow velocities in the ophthalmic artery and
      reduced flow velocities in the central retinal artery, as well as high values for
      the resistance index (RI) and pulsatility index (PI) in both arteries (p < 0.0001
      vs. controls). Biomarkers of hemolysis were found to correlate significantly with
      the RI and PI indices. In the ophthalmic artery, the reticulocyte count showed a
      moderate direct correlation with RI and with PI. In the central retinal artery,
      hemoglobin showed a strong inverse correlation with RI and with PI. CONCLUSION:
      Orbital vascular resistance, as evaluated by Doppler velocimetry, is elevated in
      patients with steady-state sickle cell anemia and shows a significant correlation
      with biomarkers of hemolysis.

PMID- 28428654
TI  - Computed tomography-guided percutaneous gastrostomy: initial experience at a
      cancer center.
AB  - Gastrostomy is indicated for patients with conditions that do not allow adequate
      oral nutrition. To reduce the morbidity and costs associated with the procedure,
      there is a trend toward the use of percutaneous gastrostomy, guided by endoscopy,
      fluoroscopy, or, most recently, computed tomography. The purpose of this paper
      was to review the computed tomography-guided gastrostomy procedure, as well as
      the indications for its use and the potential complications.

PMID- 28428656
TI  - What radiologists should know about tomographic evaluation of acute
      diverticulitis of the colon.
AB  - Acute diverticulitis of the colon is a common indication for computed tomography,
      and its diagnosis and complications are essential to determining the proper
      treatment and establishing the prognosis. The adaptation of the surgical
      classification for computed tomography has allowed the extent of intestinal
      inflammation to be established, the computed tomography findings correlating with
      the indication for treatment. In addition, computed tomography has proven able to
      distinguish among the main differential diagnoses of diverticulitis. This
      pictorial essay aims to present the computed tomography technique, main
      radiological signs, major complications, and differential diagnoses, as well as
      to review the classification of acute diverticulitis.

PMID- 28428655
TI  - Magnetic resonance imaging of the cirrhotic liver: diagnosis of hepatocellular
      carcinoma and evaluation of response to treatment - Part 2.
AB  - In the second part of this review, we will describe the ancillary imaging
      features of hepatocellular carcinoma (HCC) that can be seen on standard magnetic
      resonance imaging (MRI) protocol, and on novel and emerging protocols such as
      diffusion weighted imaging and utilization of hepatocyte-specific/hepatobiliary
      contrast agent. We will also describe the morphologic sub-types of HCC, and give
      a simplified non-invasive diagnostic algorithm for HCC, followed by a brief
      description of the liver imaging reporting and data system (LI-RADS), and MRI
      assessment of tumor response following locoregional therapy.

PMID- 28428657
TI  - X-ray and computed tomography findings in macrodystrophia lipomatosa of the foot
      with secondary osteoarthritic changes diagnosed in an elderly female: a case
      report.
AB  - Macrodystrophia lipomatosa is a rare entity that is mostly diagnosed in children.
      It has been very rarely reported in adults. Here, we describe the X-ray and
      computed tomography findings in a case of macrodystrophia lipomatosa in an
      elderly female presenting with an enlarged second toe since birth and bony
      outgrowths causing pressure effects and cosmetic problems.

PMID- 28428658
TI  - What radiologists need to know about 3D printing and its main applications in
      musculoskeletal imaging.

PMID- 28428659
TI  - Subcapsular splenic hematoma and spontaneous hemoperitoneum in a cocaine user.

PMID- 28428660
TI  - Intestinal strongyloidiasis: radiological findings that support the diagnosis.

PMID- 28428661
TI  - Diverticular disease of the colon: evolution of the therapeutic approach and the
      role of computed tomography in the evaluation of acute conditions.

PMID- 28428662
TI  - Imaging findings in chikungunya fever.

PMID- 28428663
TI  - Magnetic resonance imaging in the preoperative evaluation of breast cancer
      patients.

PMID- 28428664
TI  - Steps to Improve Journal Quality - Example of "Medical Archives".

PMID- 28428665
TI  - Brain Lesions in Children with Unilateral Spastic Cerebral Palsy.
AB  - INTRODUCTION: Unilateral spastic cerebral palsy (US CP) is the second most common
      subtype of cerebral palsy. AIM: The aim of the study was to analyze neuroimaging
      findings in children with unilateral spastic cerebral palsy. MATERIAL AND
      METHODS: The study was hospital based, which has included 106 patients with US CP
      (boys 72/girls 34, term 82/preterm 24). Neuroimaging findings were classified
      into 5 groups: Brain maldevelopment, predominant white matter injury, predominant
      gray matter injury, non specific findings and normal neuroimaging findings.
      RESULTS: Predominant white matter lesions where the most frequent (48/106,45.28%;
      term 35/preterm 13), without statistically significant difference between term
      and preterm born children (x2=0.4357; p=0.490517). Predominant gray matter
      lesions had 32/106 children, 30.19%; (term 25/preterm 7, without statistically
      significant difference between term and preterm born children (x2=0.902;
      p=0.9862). Brain malformations had 10/106 children, 9.43%, and all of them were
      term born. Other finding had 2/106 children, 1.89%, both of them were term born.
      Normal neuroimaging findings were present in14/106 patients (13.21%). CONCLUSION:
      Neuroimaging may help to understand morphological background of motor impairment
      in children with US CP. Periventricular white matter lesions were the most
      frequent, then gray matter lesions.

PMID- 28428666
TI  - Linear Short-Term Heart Rate Variability Parameters of Subjects Tobacco Cigarette
      Smokers and Subjects Nonsmokers in Preoperative Period.
AB  - BACKGROUND: Variations of heart cycles reflect complex dynamic cardiocirculatory
      regulatory systems in humans. Exposure to tobacco from cigarettes has been shown
      to elicit specific alterations of heart rate variability parameters leading to
      predominance of sympathetic and decreasing parameters of parasympathetic measures
      of cardiac autonomic nervous system tone. AIM: The aim of the trial was assessing
      differences of linear parameters of heart rate variability in subjects with habit
      of consuming of cigarettes tobacco in regard to subjects who are not consumers of
      tobacco. METHODS: Patients of ASA II class with border-line arterial hypertension
      planned for elective abdominal surgery were included in the clinical trial.
      Twenty-two subjects were allocated to group I, with history of smoking twenty or
      more cigarettes per day for five or more years, and twenty-three subjects
      nonsmokers were allocated to group II. Recordings of electrocardiogram were done
      by Holter device and later on short- term heart rate variability (five minutes
      periods) were analyzed. Parameters of time domain analysis (SDNN-standard
      deviation of NN intervals, mean RR interval, mean heart rate) and frequency
      domain measures (low frequency (LF), high frequency (HF), and LF/HF ratio) were
      analyzed. RESULTS: Baseline measures of mean NN intervals and standard deviation
      of normal to normal interval (SDNN) were slightly lower in subjects consumers of
      nicotine by cigarette tobacco smoking in regard to nonsmokers but without
      significant difference (640+-15ms vs 675+-8ms, p<0.1;45,1+-3,4 ms vs 51,4+ 3,7ms,
      p<0.08, respectively). Values of frequency domain measures (LF, HF and LF/HF
      ratio) have shown variations between two groups, but no significant difference
      was found.

PMID- 28428667
TI  - Training as an Effective Tool to Increase the Knowledge About Hand Hygiene
      Actions. An Evaluation Study of Training Effectiveness in Kosovo.
AB  - INTRODUCTION: Hand hygiene (HH) compliance with World Health Organization (WHO)
      guidelines is essential to prevent bacterial transmission and infections acquired
      from hospital settings. AIM: The aim of this study was to evaluate the impact of
      training tool of World Health Organization's (WHOs) Hand Hygiene multi modal
      campaign at all public hospitals and at the University Clinical Center in Kosovo
      (UCCK). METHOD: During February 2016, 691 questionnaires were distributed to
      health care workers. The data collection was conducted through a questionnaire
      distributed before and after training. Measurement of questions was realized
      through a 5 point Likert scale. RESULTS: The gender structure of participants
      turned out to be greater for women (n=571, 85%). The knowledge of health care
      workers differed significantly before and after the training (p<0.001),
      emphasizing that the impact of the training was important to improve the
      knowledge of participants. Thus, the average value of improvement of HCW'
      knowledge was about 41.66 %. CONCLUSION: The findings emphasized the role of the
      training to improve the knowledge of participants about hand hygiene as well as
      prevention from infection.

PMID- 28428668
TI  - Prognostic Parameters of Acute Myeloid Leukaemia at Presentation.
AB  - INTRODUCTION: The treatment response and outcome in acute myeloid leukaemia (AML)
      is heterogeneous. AIM: To analyze the prognostic parameters of AML at
      presentation. METHODS: The total sample of 44 AML patients was analyzed on the
      basis of age <55 and >=55 years, sex, WBC count <50x10/9/l and >=50x10/9/l, the
      Hb concentration <100 g/l and >=100 g/l, PLT count <100x10/9/l and >=100x10/9/l,
      Karnofsky score <60% and >60%, cytogenetics, CD56 expression, morphological type
      and types of treatment (standard and reduced induction chemotherapy, high-dose
      chemotherapy/stem cell transplantation - autologous and HLA matched, related,
      allogeneic, together and separately). RESULTS: The age <55 years, Karnofsky score
      >60% and standard induction chemotherapy statistically correlated with the higher
      complete remission (CR) rates, longer relapse free survival (RFS), lower relapse
      rate (RR), and longer overall survival (OS) (p<0.01). The difference in terms of
      CR and RR between the sexes were not statistically significant (p<0.05), however
      women had statistically lower OS comparing to men (9.71+/-4.54 months vs. 38.03+/
      9.17 months) (p<0.01). WBC count >= 50x10/9/l and the Hb concentration <100 g/l
      statistically correlated with shorter OS (p<0.05), while the WBC count
      >=50x10/9/l statistically correlated with shorter RFS (p<0.05). The PLT count
      <100x10/9/l and >=100x10/9/l was not found as prognostically significant for CR,
      RR, RFS, and OS (p<0.05). In comparison to the standard induction chemotherapy,
      both types of high dose chemotherapy/stem cell transplantation (HDT/SCT) (10/22),
      together and separately, resulted in longer RFS, lower RR, and longer OS
      (p<0.05). The frequency of cytogenetic risk was intermediate 81.6%, unfavorable
      13.2%, and favorable 5.3%, respectively. CD56 + expression statistically
      correlated with the lower PLT count, higher RR, shorter RFS, and shorter OS
      (p<0.05). Statistical analysis of the cytogenetic risk and morphological types of
      AML were not possible due to the small number of patients in stratified groups.
      CONCLUSIONS: Female sex, the WBC count >50x10/9/l, the concentration of Hb <100
      g/l, and CD56 + expression, at presentation of AML, should be considered as
      parameters of adverse risk, especially in latter decisions considering post
      remission treatment with HDT/SCT.

PMID- 28428669
TI  - Risk Factors for Osteoporosis in Postmenopausal Women.
AB  - INTRODUCTION: Scientific studies show that many factors related to lifestyles
      affect the reduction of bone mineral density and osteoporosis in postmenopausal
      women. GOAL: The goal of this study was to determine whether smoking, drinking
      coffee and alcohol in menopausal women contribute to the reduction of bone mass
      and osteoporosis, as well as the impact of physical activity on bone mass.
      MATERIAL AND METHODS: The study was carried out as case study and matched
      controls. The group of cases consisted of 100 females in postmenopausal age, in
      which by the DEXA method was newly diagnosed osteoporosis at the Clinic of
      Endocrinology, Diabetes and Metabolic Diseases, University Medical Center of RS
      during 2015-2016, while the control group consisted of 100 females in a
      postmenopausal age without diagnosed osteoporosis. The groups were matched by age
      (+/-2 years). In order to collect demographic data and information on risk
      factors for osteoporosis and lifestyle of patients was used the questionnaire
      Bone Mineral Density Questionnaire- Female of the Irish Association for
      osteoporosis. RESULTS: Testing the significance of differences in terms of
      smoking showed that the studied groups are statistically significantly different
      in terms of smoking (chi2=24.025, p=0.000). In terms of consumption of coffee, a
      statistically significant difference was found between the group of cases and
      control group (chi2=0.615, p=0.735). When observing the obtained information
      about the consumption of alcohol, we find that this preventable risk factor in
      the present study did not show as significant for osteoporosis in postmenopausal
      women (chi2=4.35, p=0.114). Statistical analysis shows that there are significant
      differences between the group of cases and control group in terms of physical
      activity (chi2=7.30, p=0.026). Analysis of the data of our study by univariate
      logistic regressions showed that smoking (p=0.000) was statistically
      significantly associated with osteoporosis, while physical activity is a
      protective factor for bone mass (p=0.036). Results of multivariate logistic
      regression showed that the independent risk factors for osteoporosis in
      postmenopausal women is smoking (OR=1.665; p=0.006). CONCLUSION: The results of
      our study show that smoking is an independent risk factor for osteoporosis in
      postmenopausal women, and physical activity is a protective factor for bone mass
      retention. Through education and certain preventive measures should be stressed
      the importance of these factors on bone health from the earliest period.

PMID- 28428670
TI  - Thyroid Autoimmunity in Patients with Chronic Urticaria.
AB  - INTRODUCTION: chronic urticaria (CU) is a skin disorder characterized by
      transient, pruritic wheals persisting for longer than 6 weeks. The
      etiopathogenesis of the disease is still unclear, but there is evidence that
      autoimmunity and endocrine dysfunction may be involved. AIM: the aim of this
      study was to determine whether chronic urticaria is statistically associated with
      thyroid autoimmunity. PATIENTS AND METHODS: in a prospective case-control study,
      we compared the frequency of thyroid auto-antibodies (thyroglobulin antibody,
      anti-Tg and thyroid peroxidase antibody, anti-TPO) in 70 patients with chronic
      urticaria and in 70 healthy volunteers. Thyroid auto-antibodies and thyroid
      hormones (thyroxine (T4), triiodthyronine (T3) and thyroid stimulating hormone
      (TSH) were measured in all subjects. RESULTS: thyroid functional abnormalities
      were found in 8 (11.43%) patients. Anti-Tg and anti-TPO were positive in 16 (23%)
      and 21 (30%) patients, respectively. In control group, only one subject (1.42%)
      had abnormalities in thyroid hormonal status, and two subjects (2.86%) had
      positive thyroid auto-antibodies. Compared with the control group, the frequency
      of both anti-Tg and anti-TPO was significantly higher in those with chronic
      urticaria (P < 0.05). CONCLUSION: this study shows a significant association
      between chronic urticaria and thyroid autoimmunity, and that tests to detect
      thyroid auto-antibodies are relevant in patients with chronic urticaria.

PMID- 28428671
TI  - Correlation of Subjective Symptoms in Patients with Benign Prostatic Hyperplasia
      and Erectile Dysfunction.
AB  - INTRODUCTION: Epidemiological studies suggest a link between the symptoms of
      lower urinary tract (LUTS) caused by benign prostatic hyperplasia (BPH) and
      erectile dysfunction (ED). Increasing expected period of life, justify the
      interest of establishing correlations LUTS / BPH and ED in order to find more
      efficient ways of treating these pathologies. GOAL: The objective was to evaluate
      the correlation of symptoms in LUTS/BPH with the degree of ED. PATIENTS AND
      METHODS: The study was conducted as a prospective study which involved males aged
      40-60 yr with present symptoms of LUTS/BPH. All study subjects underwent
      quantification of subjective symptoms through the International Prostate Symptom
      Score-IPSS and International Index of Erectile Dysfunction- IIEF-5. The first
      group of respondents had IPSS 0-8, second group IPSS 9-19 and the third group
      IPSS 20 to 35. RESULTS: The results of ANOVA (F = 112.492, p = 0.000) showed that
      there was a statistically significant difference (p <0.05) between groups in
      degree of erectile function (IIEF). Tahmane test showed that there was a
      statistically significant difference between the first and second group (p =
      0.000 <0.05), the first and third group (p = 0.000 <0.05) and the second and
      third group (p = 0.000 <0.05). Mean degree of ED correlates with IPSS. The
      results of Fisher's exact test (p = 0.000) confirmed that there was a
      statistically significant relationship (p <0.05) between the IPSS score and
      degree of erectile dysfunction (IIEF). CONCLUSION: Elderly patients have a
      significantly higher value of IPSS score compared to younger patients. The degree
      of erectile dysfunction is correlated with symptoms of IPSS score. Severity of
      symptoms of LUTS/BPH and higher IPSS score, worsens the ED. Results of IIEF-5
      score are inversely proportional with symptoms of IPSS score, and increase in
      IPSS score comes to a decline in IIEF score.

PMID- 28428672
TI  - Knowledge, Attitudes and Practices of Mothers in Kosova About Complementary
      Feeding for Infant and Children 6-24 Months.
AB  - AIM: This cross sectional study assessed knowledge, attitudes and practices
      regarding complementary feeding among mothers with children between 6-24 months
      at the national level. METHODS: The sample of 492 mothers with children between 6
      24 months, with a confidence level of 95%, the acceptable margin of 5%, the
      expected prevalence of 50% knowledge and effect of 1.3, were interviewed from all
      regions, in all Kosovo. Data were analyzed using SPSS version 17.0 and presented
      using descriptive and inferential statistics such as Chi-square with significance
      level set at 5%. RESULTS: Overall, 88.4% of respondents had good knowledge of
      complementary feeding, while only 38.4% of mothers had good practices regarding
      time for starting complementary feeding. We found association between maternal
      knowledge and level of education for complementary feeding. CONCLUSION: There is
      a need to further explore the factors responsible to improving practices for
      complementary feeding.

PMID- 28428673
TI  - Migrant General Practitioners' Experiences of Using Interpreters in Health-care:
      a Qualitative Explorative Study.
AB  - BACKGROUND: According to the UNHCR, 250 million people currently live outside
      their country of birth. The growing multicultural population poses a major
      challenge to healthcare professionals who aim to provide individualized, holistic
      care, which respects the individual's autonomy. To ensure basic rights,
      healthcare interventions should be guided by the value of benefiting others;
      individuals should be treated honestly, equally, and impartially. OBJECTIVE: To
      investigate immigrant doctors' experiences of using interpreters in the Swedish
      health-care system. MATERIAL AND METHODS: Twenty-eight doctors, 12 men and 16
      women from Bosnia and Herzegovina, Croatia, Macedonia and Serbia participated in
      four focus group interviews (FGI). The interviews were audio recorded,
      transcribed and analyzed using content analysis method. RESULTS: The best results
      in the present study were achieved in situations where a professional interpreter
      was involved. In some cases, the doctors were forced to use relatives or a
      colleague to interpret, which in many cases proved to be a mistake. The
      consequences of poor interpretation routines included payment by mistake, a
      patient paying an interpreter who refused to interpret, time spent waiting for
      another interpreter, as well as disturbances to the daily work schedule. Finding
      someone who could replace an interpreter who did not show up caused time shortage
      and increased stress. CONCLUSIONS: Improved routines and more effective
      cooperation between interpreting services and health-care centers are needed in
      order to ensure that using professional interpreters guarantees appropriate, high
      quality care. Improvements are needed to provide satisfactory health-care to
      people with limited language skills. In order to achieve this, better education
      of interpreters is needed, especially regarding cultural diversity and medical
      terminology. These improvements present complex challenges, deserving empirical
      and critical reflection in order to improve the work situation for doctors.

PMID- 28428674
TI  - Comparison of Clinical and Radiological Parameters at Knee Osteoarthritis.
AB  - INTRODUCTION: Osteoarthritis (OA) or arthrosis represents an inflammatory disease
      of joints that develops as a result of interaction of mechanical and biological
      parameters. With disease development, degenerative changes on joint cartilage can
      be noticeable that affect and cause pathological changes on other parts of a
      joint resulting in pain and dysfunction of a joint. A. E. Garrod in 1907
      described osteoarthritis as a special clinical entity and separated it from a
      rheumatoid arthritis. OA is characterized with loss of a joint cartilage,
      development of new bone tissue under affected cartilage (subchondral bone) and
      development of osteophytes on joint edge. First sign of a disease is pain after
      period of relaxation that slowly intensifies. MATERIAL AND METHODS: In this
      paper, 40 patients have been analyzed with clinical and radiological signs of OA
      of the knee joint. Radiological classification was done by Ahlback's
      classification. RESULTS: In our study female gender was more affected with
      average age of 63 years. On Ahlback classification, grade II was represented the
      most. Comparison between clinical and radiological signs showed that there was no
      significant difference between established grade of OA. Wide spectrum of visible
      radiological osteoarthritis changes on joints is in correlation with the age of
      examinees.

PMID- 28428675
TI  - Uveitis Associated with Juvenile Idiopathic Arthritis, our Observations.
AB  - INTRODUCTION: Uveitis as extra-articular manifestation of juvenile idiopathic
      arthritis (JIA) is present in 20% of children with the persistent form, in 30%
      with the extended oligoarticular form, while it is present in psoriatic and
      polyarticular rheumatoid factor (RF) negative arthritis in 10% and 14%,
      respectively. AIM: The aim of the study was to evaluate the frequency of uveitis
      and its complications in children with JIA. MATERIAL AND METHODS: A retrospective
      study was conducted with an analysis of the medical records of children with JIA
      who were treated for the last 5 years. The analysis included the following: the
      child's age and sex, age at onset of arthritis, of uveitis, complications, RF
      values and antinuclear antibodies (ANA). RESULTS: The study included 97 children
      with JIA: in 14 (14.4%) uveitis was observed; the most common form of JIA was the
      oligoarticular extended form (6/14), oligoarticular persistent form was observed
      in 5 children, while 3 children with uveitis had polyarticular RF negative JIA.
      The age of arthritis onset was lower in children with uveitis (4.7 vs 8.2 years);
      ANA positivity was more common in children with JIA and uveitis (64% vs 41%).
      Uveitis was the first manifestation of the disease for 2 children; 28.6% of
      children had clinically asymptomatic uveitis, while 42.4% of children developed
      uveitis within 4 years from the JIA onset. 8/14 children developed uveitis
      complications: 3 cases of synechia, 2 band keratopathy, 2 cataracta, 1 glaucoma.
      CONCLUSION: Uveitis as significantly present manifestation of JIA requires to
      timely recognize, treat, monitor children in order to prevent complications.

PMID- 28428676
TI  - Behavioral Problems and Emotional Difficulties at Children and Early Adolescents
      of the Veterans of War with Post-Traumatic Stress Disorder.
AB  - INTRODUCTION: Behavioral problems and emotional difficulties at children of the
      veterans of war with post-traumatic stress disorder (PTSD) have not been
      researched entirely. In our country, which has a lot of persons suffering from
      some psychological traumas, this trauma seems to continue. AIM: The aim of this
      study was to determine the exposure, manifestations of behavioral problems and
      emotional difficulties at children and early adolescents, whose fathers were the
      veterans of war demonstrating post-traumatic stress disorder symptoms.
      RESPONDENTS AND METHODS: The analyzed group comprised 120 school age children (10
      15 years of age), whose parents/fathers were the veterans of war. The children
      were divided into two groups, and each group into the following two age sub
      groups: 10-12 (children) and 13-15 (early adolescents) according to PTSD presence
      at their fathers - veterans of war. PTSD symptoms at fathers, veterans of war,
      were assessed using the Harvard Trauma Questionnaire-Bosnia and Herzegovina
      version and MKB-10 - audit of criteria. To assess the behavioral problems of
      children, the Child Behavior Checklist for parents was used, and to evaluate the
      neuroticism at children Hanes-Scale of neuroticism-extraversion was used while
      the depression level was evaluated using the Depression self-rating scale (DSRS).
      To analyze the obtained results, SPSS 17 program was used. The value p <0. 05 is
      considered significant. RESULTS: Children of fathers, the veterans of war,
      demonstrating the PTSD symptoms show more problems in activity, social and school
      conduct as well as in symptoms of behavioral problems compared to the children
      whose fathers do not demonstrate the PTSD symptoms (p<0. 001). Children of the
      war veterans demonstrating the symptoms of the post-traumatic stress disorder
      show significant difference at neuroticism sub-scales (p<0.001). Negative
      correlation between PTSD and activity, social and school conduct has been
      determined (p <0. 01), while positive correlation was determined between PTSD of
      war veterans with symptoms and neuroticism at children (p <0. 01). Depression
      symptoms are found at 17.5% children, while 28.3% are in the risky group and the
      girls demonstrate higher depression level. CONCLUSION: Children and early
      adolescents of fathers - veterans of war with post-traumatic stress disorder show
      significant differences in competencies, behavior, emotional difficulties and
      neuroticism. Significant correlation was found between psychopathology of parents
      - fathers the veterans of war and their children. Impact of psychological
      conditions of fathers - the veterans of war with post-traumatic stress disorder
      to children is strong and they represent a significant risky group for
      development of mental disorders.

PMID- 28428677
TI  - Hypothyroidism in Pediatric Population - Bosnian and Herzegovinian Situation.
AB  - INTRODUCTION: Thyroid gland diseases in children are in second place by frequency
      among all endocrine disorders. When interpreting the results of the thyroid
      function assessment it should be taken into account the significant differences
      in the concentrations of TSH, thyroid hormones, thyroid binding proteins and
      calcitonin among children of different ages. GOAL: To present the age and sex
      structure of the patients diagnosed with hypothyroidism, evaluate diagnostic
      methods for making diagnosis, evaluation of etiology of hypothyroidism, with
      special review of the therapeutic modality. PATIENTS AND METHODS: The study have
      retrospective character and includes all patients who have the diagnosis of
      hypothyroidism, but at the moment of data collection were aged 0-18 years.
      RESULTS: Distribution of patients on the basis of gender, revealed more
      significant representation of female (65.93%), and without significant difference
      in the presence of the disease in relation to age (p>0.05). Physical examination
      of the struma was not verified in the majority of cases (74; 81.32%, p<0.05)
      suffering from hypothyroidism. Ultrasound review in 22 (50%) cases confirmed the
      struma. Ultrasound findings in most cases 14 (31.81%) demonstrated diffuse struma
      and Hashimoto thyroiditis together. In relation to the etiology of hypothyroidism
      most patients belong to a group where hypothyroidism is associated with other
      diseases and conditions (27; 29.67%), but the least with congenital
      hypothyroidism with 18 (19.78%) cases. The average dose of L-thyroxine in the age
      of 0-1 months was 50 mg, 1 month-10 years 37.5 mcg, and the group of patients
      over 10 years 65 mcg. CONCLUSION: Congenital hypothyroidism has about one-fifth
      of patients. Physical examination revealed in about one fifth of patients the
      struma of the thyroid gland; TSH levels is critical for the diagnosis and
      correction of therapy in pediatric patients with hypothyroidism. Congenital
      hypothyroidism is diagnosed on average at the age of 12 days, which is optimal
      for period for therapeutic response; Substitution treatment is carried out with L
      thyroxine which is relatively reduced in doses from neonatal age onwards.

PMID- 28428678
TI  - Productive Cough in Children and Adolescents - View from Primary Health Care
      System.
AB  - Cough is one of the most common symptoms that doctor faces in working with
      pediatric population, and according to some characteristics of cough, doctors can
      often conclude localization, and sometimes even the nature of the disease that
      causes it. Cough is not only the physiological defense reaction, but a symptom of
      a disease. According to duration it can be acute, chronic and recidivist,
      recurrent and persistent, strong or discreet, caused by changes in body position
      and changes in outside temperature. Pathoanatomically it is divided into lobar,
      lobular, alveolar and interstitial, pathogenetically to bronchogenic and
      hematogenous, as well as in immuno competent and immunocompromised, and
      clinically on the local and inpatient (72 hours after hospital admission).
      Considering the contents, cough can be productive-with secretion from the
      respiratory tract, and unproductive-dry, without secretion. By auscultation
      bronchial breathing, rattle and crepitus can be heard. The primary diagnostics is
      radiological, posterior to anterior (P-A) and lateral footage of the chest.
      Laboratory findings in typical pneumonia, are characterized by leukocytosis,
      neutrophilia and shift of blood image to the left. Sedimentation is accelerated
      and C-reactive protein is elevated. The basic bacteriological diagnosis is sputum
      Gram's stain and culture of sputum. In atypical pneumonia, leukocytes are usually
      in the normal range, and it is necessary to do serological tests (IgM and IgG
      antibodies). The role of doctors in primary health care is auscultation
      differentiation of murmurs with confirmation of doubt if there is pathological
      findings by laboratory tests and treatment, depending on the type of cough.
      Treatment is essentially pharmacological, with irrefutable importance of non
      pharmacological measures.

PMID- 28428679
TI  - Mini Asymmetric Radial Keratotomy and Corneal Cross-linking for the Treatment of
      a Bilateral Stage IV Keratoconus in a 14-year-old Child.
AB  - AIM: To present the case of a 14-year-old boy with bilateral stage IV
      keratoconus, treated with a combined MARK + CXL intervention, without the need
      for a corneal transplantation. RESULTS: The left eye displays considerable
      improvements, with a follow-up of 13.5 years: Kmax is decreased by 5.53 D, Kmed
      is decreased by 1.95 D and thinnest pachymetry is increased by 106 um. The right
      eye shows equally remarkable parameters, with a follow-up of 9.5 years: Kmax is
      decreased by 8.16 D, Kmed is decreased by 0.38 D and thinnest pachymetry is
      increased by 52 um. Keratoconus has been halted and the patient has a binocular
      best corrected visual acuity of -0.079 LogMAR (12/10). CONCLUSION: The MARK + CXL
      combined intervention, known as the "Rome Protocol", was successful in halting a
      bilateral stage IV keratoconus and improving visual acuity in a very young
      patient, with long-term follow-up. Conservative treatments should always be
      privileged when treating very young patients with developed stages of the
      pathology.

PMID- 28428680
TI  - Coexistence of Condylomata Acuminata with Warty Squamous Cell Carcinoma and
      Squamous Cell Carcinoma.
AB  - INTRODUCTION: Condyloma acuminatum has previously been considered to be a benign
      growth with no malignant potential, but a review of the literature supports the
      concept that condylomata acuminata may precede or be associated with invasive
      squamous cell carcinoma (ISCC) or warty squamous cell carcinoma (WSCC). CASE
      REPORT: We present a clinical case of a 58-year old woman with large, slow
      growing, exophytic tumor of external genitalia shaped like a cauliflower with the
      propagation to both legs and behind. We performed multiple biopsies to detect
      potential malignancy but malignancy was not confirmed histologically. The
      presence of HPV (human papilloma virus) low and high risk was discovered.
      Inguinal lymph nodes were enlarged both sides, but cytologic examination
      identified no malignant cells. The patient was initially treated by the loop
      electro surgical excision procedure (LEEP) and podophilin solution on the rest of
      the condylomas. Condyloma acuminatum was confirmed histologically. Later, we
      performed a wide surgical excision of the rest of the condylomas. The new changes
      on the previously treated region were removed using LEEP. WSCC and ISCC were
      confirmed histologically so were radical vulvectomy and inguinal lymphadenectomy
      performed. The patient was advised to remain under close follow-up.

PMID- 28428681
TI  - Frequency of Bacterial Samples from Patients with Chronic Acquired Nasolacrimal
      Duct Obstruction.

PMID- 28428683
TI  - Does pre-school improve cognitive abilities among children with early-life
      stunting? A longitudinal study for Peru.
AB  - Several studies in developing countries have found that children who experience
      growth faltering in the first years of life show lower cognitive abilities than
      their peers. In this study, we use the Young Lives longitudinal dataset in Peru
      to analyze if attending pre-school affects cognitive abilities at age five years,
      and if there is an interaction with HAZ at age one year. Using instrumental
      variables we found, for receptive vocabulary, a positive effect of attending
      Jardines (formal) pre-schools; the effect of attending PRONOEI (community-based)
      pre-schools was not significant. More years attending Jardines was more
      beneficial for children who were better nourished. We suggest working to improve
      the quality of PRONOEIs, and with teachers on targeting children of lower
      nutritional status.

PMID- 28428682
TI  - Neuropathogenesis of Zika Virus Infection : Potential Roles of Antibody-Mediated
      Pathology.
AB  - Zika virus (ZIKV) is an enveloped, positive-sense, single-stranded RNA virus that
      belongs to the genus Flavivirus, family Flaviviridae, which includes many human
      and animal pathogens, such as dengue virus (DENV), West Nile virus, and Japanese
      encephalitis virus. In the original as well as subsequent experimental and
      clinical reports, ZIKV seems to have moderate neurotropism (in animal models) and
      neurovirulence (in human fetuses), but no neuroinvasiveness (in human adults).
      Intrauterine ZIKV infection (viral pathology) has been linked to an increased
      incidence of microcephaly, while increased Guillain-Barre syndrome (GBS)
      following ZIKV infection is likely immune-mediated (immunopathology). Clinically,
      in ZIKV infection, antibodies against other flaviviruses, such as DENV, have been
      detected; these antibodies can cross-react with ZIKV without ZIKV neutralization.
      In theory, such non-neutralizing antibodies are generated at the expense of
      decreased production of neutralizing antibodies ("antigenic sin"), leading to
      poor viral clearance, while the non-neutralizing antibodies can also enhance
      viral replication in Fc receptor (FcR)-bearing cells via antibody-dependent
      enhancement (ADE). Here, we propose three potential roles of the antibody
      mediated pathogenesis of ZIKV infection: 1) cross-reactive antibodies that
      recognize ZIKV and neural antigens cause GBS; 2) ZIKV-antibody complex is
      transported transplacentally via neonatal FcR (FcRn), resulting in fetal
      infection; and 3) ZIKV-antibody complex is taken up at peripheral nerve endings
      and transported to neurons in the central nervous system (CNS), by which the
      virus can enter the CNS without crossing the blood-brain barrier.

PMID- 28428685
TI  - Prospects of Molecular Biotechnology in Diagnostics: Step Towards Precision
      Medicine.

PMID- 28428684
TI  - Innate Immunity of Adipose Tissue in Rodent Models of Local and Systemic
      Staphylococcus aureus Infection.
AB  - Background. The role of adipose tissue in systemic inflammation during bacterial
      infection is unclear. Effects of Staphylococcus aureus infection on adipocytes in
      rodent models of experimental endocarditis and peritonitis, the impact of S.
      aureus infection on gene expression in epididymal and subcutaneous adipose
      tissue, and effects of S. aureus infection on the toll-like receptor-2- (TLR2-)
      cathelicidin pathway in vivo and in vitro were investigated. Material and
      methods. The rat model of catheter-induced S. aureus endocarditis and the mouse
      model of S. aureus-induced peritonitis were used for infection experiments, gene
      expression profiling in adipose tissue, and measurement of cytokines. 3T3-L1
      adipocytes were analyzed for expression of the TLR2-cathelicidin pathway.
      Results. Upon systemic bacterial infection by S. aureus, there is a shift from
      anti- to proinflammatory cytokines in serum and in adipose tissue gene
      expression. The TLR2-cathelicidin pathway is increasingly expressed during
      adipocyte differentiation in vitro and is induced upon stimulation by synthetic
      lipopeptides. Conclusions. Systemic infection by Gram-positive bacteria induces
      proinflammatory transformation of adipose tissue sites distinct from infection
      sites, documented on the levels of gene expression and secreted mediators. The
      TLR2-cathelicidine pathway is expressed and highly inducible in adipocytes in
      vitro. Lipopeptides are important immune-modulators of adipocytes in both gene
      expression and protein secretion.

PMID- 28428686
TI  - Aflatoxins: Implications on Health.
AB  - Environmental occurrence of Aspergillus and other fungal spores are hazardous to
      humans and animals. They cause a broad spectrum of clinical complications.
      Contamination of aflatoxins in agri-food and feed due to A. flavus and A.
      parasiticus result in toxicity in humans and animals. Recent advances in
      aspergillus genomics and aflatoxin management practices are encouraging to tackle
      the challenges posed by important aspergillus species.

PMID- 28428687
TI  - Lysyl Oxidase: Its Diversity in Health and Diseases.
AB  - The mechanical properties of extracellular matrix (ECM) and connective tissues is
      largely dependent on the collagen and elastin structure. Lysyl oxidase (LOX)
      plays a critical role in the formation and repair of the ECM by oxidizing lysine
      residues in elastin and collagen, thereby initiating the formation of covalent
      cross linkages which stabilize these fibrous proteins. Due to its multiple
      functions both extracellularly and intracellularly, lysyl oxidase is involved in
      several processes in the tumorigenic pathway, in many different cancer types and
      stages. Alteration in LOX activity is implicated in many diseases and disorders
      including inflammation and inflammatory diseases, fibrosis of distinct organs and
      fibrotic disorders, cancer promotion and progression. There are only sparse
      reports of mutations or epigenetic alterations in the LOX gene. This review
      provides the recent clinical developments in the molecular mechanisms and
      pathologic process, pointing out LOX as a potential therapeutic target in
      translational medicine.

PMID- 28428688
TI  - Modulation of Angiogenesis, Proliferative Response and Apoptosis by beta
      Sitosterol in Rat Model of Renal Carcinogenesis.
AB  - As expanded understanding of molecular tumor characteristics, which drive renal
      cancer growth and progression gives a promising future for renal carcinoma
      therapy. The objective of the present study was designed to examine the effect of
      beta-sitosterol on a rat model of experimental renal carcinogenesis. Renal
      carcinogenesis was induced in rats treated with N-diethylnitrosamine (DEN; 200
      mg/kg bw single i.p., injection) and ferric nitrilotriacetate (Fe-NTA; 9 mg Fe/kg
      bw i.p., twice a week for 16 weeks). beta-sitosterol pretreatment (20 mg/kg bw in
      0.1 % carboxymethyl cellulose (CMC) p.o., thrice a week for 24 weeks) was started
      2 weeks before the exposure to carcinogens. Expression of angiogenesis marker
      (VEGF), proliferative markers (cyclin D1, PCNA) and apoptotic markers (Bcl-2,
      Bax, caspase-3 and caspase-9) were analyzed to assess the anti-cancer potential
      of beta-sitosterol in renal carcinogenesis model. mRNA and protein expression
      changes were determined by qRT-PCR, Western blotting, ELISA technique and
      immunohistochemistry. Our results showed that oral administration of beta
      sitosterol pretreatment significantly (P < 0.05) reversed the expression of all
      the above mentioned markers and histological features which have been modified by
      renal carcinogen. It is concluded that, the protective effects of beta-sitosterol
      against renal cancer is associated with the induction of apoptosis and the
      inhibition of cellular proliferation.

PMID- 28428689
TI  - Experimental Validation of Antidiabetic Potential of Cayratia trifolia (L.)
      Domin: An Indigenous Medicinal Plant.
AB  - The present study was undertaken to evaluate antidiabetic and antioxidant
      activities of Cayratia trifolia root extract against streptozotocin induced
      diabetes in experimental rats to scientifically validate its use against diabetes
      in some parts of India. Ethanolic extract, showing the highest activity in in
      vitro experiments, was prepared in saline and administered orally to
      streptozotocin induced albino Wistar diabetic rats for 21 days. Biochemical
      parameters liver and muscles glycogen and in vivo antioxidant activity in normal,
      diabetic control, standard (metformin) and treated animals were determined and
      compared. Attempt was made to isolate, purify and characterize one of the major
      secondary metabolites in extract by range of chromatographic and spectroscopic
      techniques. Treatment of streptozotocin induced diabetic rats with ethanolic root
      extract (500 mg/kg) caused significant (P < 0.01) reduction in blood glucose (312
      178 mg/dL), increase in body weight (181-219 g) and serum insulin (1.28-2.26
      IU/dL). It also maintained lipid profile and tests of liver and kidney functions
      within normal range as compared to diabetic control rats and almost at par with
      standard drug metformin. The oxidative stress induced decline in glutathione and
      catalase in liver and kidney tissues showed recovery nearly to normal level as a
      function of treatment. The GC-MS profile of the extract showed relatively high
      concentration of beta-sitosterol which was characterized by different
      spectroscopic and chromatographic techniques. The result scientifically and
      comprehensively validate the reported use of roots of this indigenous plant
      against diabetes. A strong antioxidant activity of the ethanolic root extract
      suitably compliments the antidiabetic effect.

PMID- 28428690
TI  - Implications of ACE (I/D) Gene Variants to the Genetic Susceptibility of Coronary
      Artery Disease in Asian Indians.
AB  - Angiotensin-1-converting enzyme (ACE) gene has established substantial attention
      in the recent years as a candidate gene for hypertension, cardiovascular diseases
      and type 2 diabetes. The aim of the present study was to investigate the
      association of ACE (I/D) polymorphism with coronary artery disease (CAD) in a
      north Indian population. A total of 662 subjects (330 CAD patients and 332
      healthy controls) were examined for association of ACE gene (I/D) polymorphism
      and environmental risk factors. The mean age of the CAD patients and control
      subjects was 60.53 +/- 8.6 years and 56.55 +/- 7.7 years, respectively (p =
      0.000). Anthropometric and demographic data showed BMI values significantly
      higher among CAD patients and control subjects (26.98 +/- 4.9 vs 24.04 +/- 4.7, p
      = 0.000). We observed pronounced central obesity in both CAD patients and
      controls, even at the lowest BMI values (<23 kg/m2). Dyslipidemia was highly
      prevalent in CAD patients compared to control subjects. Genotypic data showed
      significantly higher frequency of DD genotype in CAD patients than that of
      control subjects (40 vs 28.3 %). No significant difference was observed in the
      distribution of ID genotypes between CAD patients and control subjects. Logistic
      regression analysis of data demonstrate that DD genotype was associated with 1.8
      fold increased risk of development of CAD in Asian Indians (OR 1.8; 95 % CI 1.22
      2.66; p = 0.003). The frequency of D allele was significantly higher in CAD
      patients (p = 0.001). No significant difference was observed in the clinical and
      biochemical characteristics of CAD patients and controls when the data was
      stratified according to the genotypes of ACE gene. In conclusion, DD genotype of
      ACE gene may be associated with increased risk of CAD in Asian Indian population.

PMID- 28428691
TI  - Relationship Between Xanthine Oxidase, Ischemia Modified Albumin, Nitric Oxide
      with Antioxidants in Non Pregnants, Pre and Post-delivery of Normal Pregnants and
      Preeclampsia.
AB  - Preeclampsia is a multisystem disorder involves altered homeostasis of oxidants
      antioxidants, inflammatory process and endothelial dysfunction. The present study
      aim was to determine the levels of oxidative stress parameters (malondialdehyde,
      protein carbonyl, ischemia modified albumin and xanthine oxidase), nutrient
      antioxidants (vitamin C and vitamin E), enzyme antioxidants (catalase, superoxide
      dismutase, glutathione peroxidase glutathione reductase), total antioxidant
      status (TAS) and its association with nitric oxide. The study population consists
      of three groups, non pregnants (Group 1, n = 57), normotensive pregnants (Group
      2, n = 57) and Preeclampsia (Group 3, n = 57). Group 2 and 3 were followed after
      delivery within 48 h. In preeclampsia xanthine oxidase, malondialdehyde and uric
      acid levels were significantly increased (p < 0.001), while TAS decreased (p <
      0.05) when compared to normotensive pregnant and non pregnant. Catalase,
      glutathione reductase levels were increased (p < 0.005) and vitamin E, super
      oxide dismutase levels were decreased (p < 0.001) in preeclampsia when compared
      to normal pregnants. Receiver operating characteristics curve analysis showed
      area under curve for xanthine oxidase (0.8), malondialdehyde (0.804), Uric acid
      (0.84), ischemia modified albumin (0.92) and catalase (0.88) which indicated as
      good markers in preeclampsia. Amongst, ischemia modified albumin is a better
      marker of intrauterine hypoxic reperfusion risk with sensitivity 87.7 % and
      specificity 91.2 %. The increased hydrogen peroxide from xanthine oxidase adds to
      oxidative stress and increased catalase activity in preeclampsia represents
      combating action. Increased oxidative stress, decreased TAS and its apparent
      reversible changes evinced within 48 h after delivery in preeclampsia illustrated
      that placental abnormality is the contributing factor in the pathogenesis.

PMID- 28428692
TI  - The Appraisement of Antioxidant and Oxidant Status in Women Undergoing Surgical
      Menopause.
AB  - The present study was undertaken to study the impact of surgical menopause on
      oxidant and antioxidant status in relation to estrogen levels after 3 months of
      surgery. Total 130 women who had undergone total hysterectomy (TH) with or
      without bilateral salpingo-oophorectomy (BSO) were included in this study. The
      oxidant status was assessed by measuring plasma levels of malondialdehyde and
      antioxidant status was assessed by measuring superoxide dismutase, catalase,
      glutathione, glutathione peroxidase, estrogen, and Vitamin A, E and C levels. The
      malondialdehyde level was significantly increased (p < 0.05) in all women who
      underwent TH with or without BSO. Significant increased levels of superoxide
      dismutase were observed in women who underwent TH with BSO. The blood glutathione
      levels were significantly decreased in women after TH only but significantly
      increased in women who had undergone TH with BSO. The levels of estrogen, vitamin
      E and vitamin C were significantly decreased in women who underwent TH with BSO.
      The catalase, GPx and vitamin A did not differ significantly in all groups. The
      result suggests that surgical menopause is associated with oxidative stress which
      reiterates the fact that ovaries retain some function even after menopause.

PMID- 28428693
TI  - The Association Between Small Dense Low Density Lipoprotein and Coronary Artery
      Disease in North Indian Patients.
AB  - Pathogenesis of coronary artery disease (CAD) is multi-factorial and several
      conventional risk factors have been ascribed; LDL-C being one of the important
      risk factor. However Indian population studies with established CAD often show
      LDL levels within normal range in patients with proven CAD. We hypothesized that
      Small dense low density lipoprotein (sdLDL) being more atherogenic might
      correlate more strongly to the occurrence and severity of CAD. The aim of the
      study was to evaluate the association between serum small dense LDL level and
      angiographically documented coronary artery disease. This is a cross sectional
      case control study in which sdLDL were measured in 126 patients with CAD and in
      64 patients without CAD. Total cholesterol, HDL Cholesterol, LDL cholesterol and
      triglycerides were measured by standard methods along with other traditional risk
      factors. Direct quantitative measurement of sdLDL was done by enzymatic analysis.
      Mean sdLDL level was higher in patients with coronary stenosis than patients
      without coronary stenosis (16.3 +/- 6.8 vs. 10.1 +/- 5.7 mg/dL respectively, (p <
      0.001). There was significant correlation between mean sdLDL and severity of CAD
      as assessed by syntax score with mean sdLDL level in low, intermediate and high
      syntax score being 15.0 +/- 5.8, 20.1 +/- 6.7 and 22.7 +/- 7.3 mg/dL respectively
      (p value <0.001). A cut off value of 10.02 mg/dL was associated with presence of
      CAD (95 % CI 0.82-0.93, p < 0.001) using ROC curve. In conclusion Indian patients
      with established CAD have higher sdLDL levels compared to individuals without CAD
      despite having comparable LDL levels.

PMID- 28428694
TI  - A Microarray Immunoassay for Serum Thyrotropin and Thyroglobulin Using Antibodies
      Immobilized on Track-Etched Membranes.
AB  - Serum thyroglobulin (Tg) and thyroid stimulating hormone (TSH) measurements have
      evolved as important analytes for monitoring the prognosis of patients with
      differentiated thyroid cancer, post-thyroidectomy. Individual analyte immunoassay
      is the current practice in clinical pathology, but the simultaneous assay for all
      relevant analytes for a given disease, can reduce assay costs, improve patient
      compliance and give the clinician more information for an unequivocal diagnosis.
      Microarray immunoassay (MI) can achieve this goal and, hence, we have developed
      and validated a immuno-radiometric MI for quantitation of serum TSH and Tg by
      using highly micro-porous polycarbonate (PC) track-etched membranes (TEM) to
      immobilize the monoclonal anti-TSH and polyclonal anti-Tg antibodies in ~1 mm
      diameter spots. Non-competitive immunoassays were performed using mixture of 125I
      labeled monoclonal anti-TSH and anti-Tg antibodies. Phosphorimager was used to
      quantify the bound radioactivity. TSH and Tg were detected with detection limit
      of 0.07 uIU/ml and 0.13 ng/ml respectively, which is lower than the clinically
      required cut-off level. The assay showed: acceptable intra-assay precision within
      20 % and recovery in the range of 76-111.2 %. MI compared well with the
      established immunoradiometric assay (IRMA) with r = 0.98, p < 0.01 (n = 41). No
      cross-reactivity was seen between the immobilized antibodies. Although two
      hormones are addressed in this report, MI using PC TEM and isotopic/non-isotopic
      tracers has the potential for highly automated multiplexed analysis.

PMID- 28428695
TI  - Increased Oxidatively Modified Forms of Albumin in Association with Decreased
      Total Antioxidant Activity in Different Types of Hypertensive Disorders of
      Pregnancy.
AB  - Protein oxidation has been demonstrated in preeclampsia, but this finding has not
      been established in other hypertensive disorders in pregnancy (HDP). The present
      study comparatively evaluated ischemia modified albumin (IMA) and advanced
      oxidation protein products (AOPP) in different HDP and investigated their
      association with total antioxidant activity (AOA) and total thiols. There was a
      significant increase in AOPP and IMA, a significant decrease in AOA, total thiols
      and albumin in every HDP compared to controls. Among HDP groups, eclampsia
      patients showed more significant change in each of the parameter. IMA and AOPP
      were negatively associated with AOA in every HDP and with total thiols only in
      eclampsia. The present study supports the hypothesis of oxidative stress, as
      evidenced by increased protein oxidation, decreased antioxidant status and
      significant negative association between protein oxidation and AOA in every HDP.
      The imbalance of prooxidants and antioxidants was further augmented in eclampsia.

PMID- 28428696
TI  - Gamma Amino Butyric Acid Attenuates Brain Oxidative Damage Associated with
      Insulin Alteration in Streptozotocin-Treated Rats.
AB  - The aim of the current study was to evaluate the role of gamma-amino butyric acid
      (GABA) in insulin disturbance and hyperglycemia associated with brain oxidative
      damage in streptozotocin-treated rats. Streptozotocin (STZ) was administered to
      male albino rats as a single intraperitoneal dose (60 mg/kg body weight). GABA
      (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to
      STZ-treated-rats. Male albino rats Sprague-Dawley (10 +/- 2 weeks old; 120 +/- 10
      g body weight) were divided into 4 groups of 6 rats and treated in parallel. (1)
      Control group: received distilled water, (2) GABA group: received GABA, (3) STZ
      group: STZ-treated rats received distilled water, (4) STZ + GABA group: STZ
      treated rats received GABA. Rats were sacrificed after a fasting period of 12 h
      next last dose of GABA. The results obtained showed that STZ-treatment produced
      hyperglycemia and insulin deficiency (similar to type1 Diabetes). These changes
      were associated with oxidative damage in brain tissue and notified by significant
      decreases of superoxide dismutase and catalase activities in parallel to
      significant increases of malondialdehyde and advanced oxidation protein products
      levels. The histopathology reports also revealed that STZ-treatment produced
      degeneration of pancreatic cells. The administration of GABA to STZ-treated rats
      preserved pancreatic tissue with improved insulin secretion, improved glucose
      level and minimized oxidative stress in brain tissues. It could be concluded that
      GABA might protect the brain from oxidative stress and preserve pancreas tissues
      with adjusting glucose and insulin levels in Diabetic rats and might decrease the
      risk of neurodegenerative disease in diabetes.

PMID- 28428697
TI  - Geraniol Inhibits Endometrial Carcinoma via Downregulating Oncogenes and
      Upregulating Tumour Suppressor Genes.
AB  - Endometrial carcinoma is the fourth most abundant cancer worldwide in women.
      Female Wistar rats were segregated into five groups: group I-control, group II
      MNNG (N-methyl-N'-nitro-N-nitrosoguanidine-150 mg/kg) administered through
      intravaginal detention of cotton absorbent, group III-geraniol (GOH) only, group
      IV-GOH-pretreated (7 days before the start of MNNG administration); and group V
      Co-administration of geraniol with MNNG. In this study, reverse transcriptase-
      PCR of K-ras, MAPK, PI3K, Wnt/beta-catenin genes, TGF-beta and expressions of
      PCNA, PTEN, progesterone receptor and E-cadherin by Western blotting were
      performed from endometrial cancer tissue and control tissues. The mRNA
      expressions of K-ras, MAPK, PI3K, Wnt/beta-catenin and TGF-beta were amplified in
      MNNG induced group. Oral administration of GOH (both pre and co-administration)
      reversed the mRNA expression towards normal. The reversibility is more
      predominant in pretreatment groups (p < 0.05). The expression of PCNA was
      upregulated and downregulation of PTEN, progesterone receptor and E-cadherin was
      noticed in MNNG induced rats. Pre and co-administration of GOH significantly
      reversed the expression pattern of proteins. GOH treatment is more effective in
      pretreatment groups (p < 0.05). These results provide powerful evidences that GOH
      could influence modulation of MAPK pathways and Wnt signalling pathways in the
      prevention of endometrial carcinoma in rats.

PMID- 28428698
TI  - Circadian Periodicity of Circulating Plasma Lipid Peroxides, Uric Acid and
      Ascorbic Acid in Renal Stone Formers.
AB  - Circadian periodicity of plasma lipid peroxides and serum ascorbic acid and uric
      acid levels were studied in one hundred renal stone formers (55 women and 45 men;
      age 20-60 years) and 50 clinically healthy volunteers (21 women and 29 men; age
      21-45 years) with diurnal activity from 06:00 to 22:00 and nocturnal rest. A
      marked circadian variation was demonstrated by population-mean-cosinor for all
      studied variables in stone formers and healthy subjects. By comparison to the
      healthy controls, parameter tests indicate that the stone formers had a higher
      MESOR (+/-SE) of MDA (2.90 +/- 0.03 vs. 2.28 +/- 0.06; F = 94.929, p < 0.001), a
      lower MESOR of serum ascorbic acid (0.722 +/- 0.010 vs. 0.839 +/- 0.10; F =
      32.083, p < 0.001), and a similar MESOR of serum uric acid. Furthermore, the
      patients also differed from the healthy subjects in terms of their circadian
      amplitude and acrophase (tested jointly) of all three variables (p < 0.001). The
      demonstration herein of a circadian rhythm in MDA, serum ascorbic and uric acid
      suggests that these variables could also serve as markers to optimize the timing
      of treatment and to assess the patient's response to treatment for further
      management.

PMID- 28428699
TI  - Putative Role of Cardio Metabolic Risk Among Poorly Controlled Asthmatics in
      South Indian Population.
AB  - Mortality and morbidity attributed to asthma remains to be the biggest nightmare
      worldwide. Hence, the study was aimed to compare the cardio metabolic risk
      factors as assessed by Body mass index (BMI), waist hip ratio (WHR), serum
      triacylglycerol and uric acid in well controlled and poorly controlled asthmatics
      and to correlate these parameters with the severity of asthma. A case control
      study was conducted on 90 subjects who were segregated into well controlled
      asthmatics (n = 30) and poorly controlled asthmatics (n = 30) who were diagnosed
      based on Global initiative for Asthma management guidelines and healthy
      volunteers (n = 30). Centrifuged fasting venous blood samples were used for
      biochemical analysis, pulmonary function test, BMI, and waist hip ratio (WHR)
      were measured. The statistical analysis was done using SPSS version 17. There was
      a significant increase in BMI, WHR, lipid profile, serum uric acid and decrease
      in forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC in
      poorly controlled asthmatics. There was a significant association between FEV1
      and serum uric acid, BMI and Triacylgycerol in poorly controlled asthmatics.
      Poorly controlled asthmatics have greater risk of developing cardiometabolic
      problems. Serum uric acid can be used as one of the severity markers in asthma to
      assess cardio metabolic risk.

PMID- 28428700
TI  - Preparation, Characterization and Cytotoxic Effects of Pegylated Nanoliposomal
      Containing Carboplatin on Ovarian Cancer Cell Lines.
AB  - Carboplatin is a chemotherapeutic agent used against various malignancies such as
      ovarian carcinoma. The aim of this study is to improve the therapeutic efficacy
      of carboplatin using pegylated liposomal nanocarriers. Nanoparticles were
      synthesized using thin film hydration technique and characterized for shape
      morphology, particle size, zeta potential and drug-release properties. In the
      next step, A2780S and A2780CP ovarian cancer cell lines were used to determine
      the efficacy of nanodrug by MTT assay. The particle size and zeta potential of
      nanodrug were measured 244.3 +/- 19.6 nm and -22.9 +/- 1.7 mV, respectively. High
      encapsulation capacity (78.6 +/- 3.7 %) confirmed the efficiency of technique.
      The cytotoxicity results also showed that nanodrug compared to free drug improve
      the efficacy of carboplatin against both A2780S (P < 0.01) and A2780CP (P < 0.05)
      cell lines. In conclusion, the findings of our study suggested pegylated
      liposomal nanocarriers are proper for carboplatin delivery to ovarian cancer cell
      lines A2780S and A2780CP.

PMID- 28428701
TI  - Association of Cholesteryl Ester Transfer Protein (CETP) Gene -629C/A
      Polymorphism with Angiographically Proven Atherosclerosis.
AB  - Association of cholesteryl ester transfer protein (CETP) Gene -629C/A
      Polymorphism with angiographically proven atherosclerosis CETP gene has been
      linked to CAD risk via its role in HDL and LDL metabolism. There is no agreement
      of whether CETP is atherogenic or not. Furthermore, various genotypes of CETP
      gene have been associated with CETP levels and thus with atherosclerosis risk.
      Our aim was to study the association of CETP -629C/A gene polymorphism with CETP
      and HDL levels and their association if any with atherosclerosis. Study
      population consisted of angiographically documented 50 cases with coronary artery
      atherosclerosis and 50 controls negative for atherosclerosis of coronary artery.
      Serum lipid profile was measured on SYNCHRON CX-9 using standard kits. Serum CETP
      levels were measured by ELISA method. CETP -629C/A gene polymorphism was studied
      using PCR-RFLP method. There was no significant difference in lipid profile of
      the two groups. However, serum CETP level was significantly higher (46.44 +/-
      21.75 ng/ml) in cases than controls (37.10 +/- 21.92 ng/ml) with p value =0.035.
      The frequency of -629A allele was higher (0.85) in cases than that of controls
      (0.81). Homozygosity of A allele was more in subjects with atherosclerosis of
      coronary artery. We conclude that CETP is atherogenic and could be used as
      atherogenic risk predictor in angiographically proven atherosclerosis. Also A
      allele of -629C/A polymorphism is more prevalent in cases; indicating its effect
      on expression of CETP gene.

PMID- 28428702
TI  - DRD4 and DAT1 VNTR Genotyping in Children with Attention Deficit Hyperactivity
      Disorder.
AB  - The dopamine receptor-D4 and the dopamine transporter have been investigated for
      their role in attention deficit hyperactivity disorder (ADHD) in children.
      Reports of their genetic association with ADHD have shown mixed results. The aim
      of the study was to evaluate the association of variable number tandem repeats
      (VNTRs) of the DRD4 and DAT1 genes with ADHD in children. A pilot 1:1 case
      control study, with 44 clinically confirmed ADHD cases and 44 age/gender matched
      healthy controls, was conducted at a tertiary care centre in Mumbai. Variable
      number tandem repeats of DRD4 exon 3, DAT1 intron 8 and 3'UTR were genotyped by
      PCR-AGE. Several allele repeats of the genes were observed in the screened
      subjects. Statistical significance was observed for the 10R/10R genotype of the
      DAT1 3'UTR VNTR between cases and controls.

PMID- 28428704
TI  - Lead Poisoning Due to Herbal Medications.
AB  - Lead ranks as one of the most serious environmental poisons all over the world
      amongst toxic heavy metals with no known biological function useful for the human
      body. A case of lead toxicity due to consumption of herbal medicine is being
      discussed. The case presented with gastrointestinal complaints and history of
      intake of herbal medicines for diabetes control for past 8 months. The analysis
      of the powdered herbal medicine procured from ayurveda practitioner was found to
      have high content of lead responsible for the lead toxicity. The patient is under
      regular followup. He has improved symptomatically on chelating therapy and blood
      lead levels have gradually improved. Regular awareness programs should be
      conducted in the population regarding possible exposure through home made herbal
      remedies so that general public can be made aware of the dangerous side effects
      of lead and other heavy metals on health.

PMID- 28428703
TI  - Comparative Study of Two ELISA Kits for Estimation of Antibodies to Hepatitis B
      Virus in Human Normal Immunoglobulin and Specific Immunoglobulin Intended for
      Intravenous or Intramuscular Use.
AB  - Current study is conducted to evaluate method verification of two locally
      available kits manufactured by DSI & BIORAD for quantitative estimation of
      Hepatitis B virus antibodies in human normal immunoglobulin by using
      International standard of National Institute of Biological Standards and Control.
      Four analyst perform five sets of test in duplicate analysing accuracy,
      precision, and limit of detection, sensitivity and specificity. Our results
      suggest that both DSI and BIORAD kits fulfil the validation criteria and are
      sensitive to detect up to 10 mIU concentration precisely and accurately. DSI kit
      is more precise at concentration 100 mIU and economically 4-5 times cheaper in
      local market; on the other hand, BIORAD kits provide larger detection range up to
      1000 mIU.

PMID- 28428705
TI  - Methemoglobinemia: Living with Dormant Devil.
AB  - Methemoglobin is an oxidized form of hemoglobin. NADH methemoglobin reductase
      deficiency or inactivity is the cause of methemoglobin. Excessive production,
      resulting in accumulation, causes methemoglobinemia. It can be congenital or
      acquired. We present a case of dormant congenital methemoglobinemia detected
      accidentally on preoperative assessment, due to low oxygen saturation even at
      F1O2-1.0 associated with central cyanosis. The patient had 27.7 % methemoglobin,
      living his life without any complications. The patient was operated upon
      successfully for tympanoplasty and mastoidectomy under local anesthesia by taking
      proper precautions.

PMID- 28428706
TI  - Gastroesophageal reflux disease and morbid obesity: To sleeve or not to sleeve?
AB  - Laparoscopic sleeve gastrectomy (LSG) has reached wide popularity during the last
      15 years, due to the limited morbidity and mortality rates, and the very good
      weight loss results and effects on comorbid conditions. However, there are
      concerns regarding the effects of LSG on gastroesophageal reflux disease (GERD).
      The interpretation of the current evidence is challenged by the fact that the LSG
      technique is not standardized, and most studies investigate the presence of GERD
      by assessing symptoms and the use of acid reducing medications only. A few
      studies objectively investigated gastroesophageal function and the reflux profile
      by esophageal manometry and 24-h pH monitoring, reporting postoperative
      normalization of esophageal acid exposure in up to 85% of patients with
      preoperative GERD, and occurrence of de novo GERD in about 5% of cases. There is
      increasing evidence showing the key role of the surgical technique on the
      incidence of postoperative GERD. Main technical issues are a relative narrowing
      of the mid portion of the gastric sleeve, a redundant upper part of the sleeve
      (both depending on the angle under which the sleeve is stapled), and the presence
      of a hiatal hernia. Concomitant hiatal hernia repair is recommended. To date,
      either medical therapy with proton pump inhibitors or conversion of LSG to
      laparoscopic Roux-en-Y gastric bypass are the available options for the
      management of GERD after LSG. Recently, new minimally invasive approaches have
      been proposed in patients with GERD and hypotensive LES: the LINX(r) Reflux
      Management System procedure and the Stretta(r) procedure. Large studies are
      needed to assess the safety and long-term efficacy of these new approaches. In
      conclusion, the recent publication of pH monitoring data and the new insights in
      the association between sleeve morphology and GERD control have led to a wider
      acceptance of LSG as bariatric procedure also in obese patients with GERD, as
      recently stated in the 5th International Consensus Conference on sleeve
      gastrectomy.

PMID- 28428707
TI  - Advanced pancreatic ductal adenocarcinoma - Complexities of treatment and
      emerging therapeutic options.
AB  - Pancreatic ductal adenocarcinoma is a devastating disease with a poor prognosis
      regardless of stage. To date the mainstay of therapy for advanced disease has
      been chemotherapy with little incremental improvements in outcome. Despite
      extensive research investigating new treatment options the current practices
      continue to utilise fluorouracil or gemcitabine containing combinations. The need
      for novel therapeutic approaches is mandated by the ongoing poor survival rates
      associated with this disease. One such approach may include manipulation of
      ribosome biogenesis and the nucleolar stress response, which has recently been
      applied to haematological malignancies such as lymphoma and prostate cancer with
      promising results. This review will focus on the current therapeutic options for
      pancreatic ductal adenocarcinoma and the complexities associated with developing
      novel treatments, with a particular emphasis on the role of the nucleolus as a
      treatment strategy.

PMID- 28428708
TI  - Indoleamine 2,3-dioxygenase: As a potential prognostic marker and
      immunotherapeutic target for hepatocellular carcinoma.
AB  - Tumor cells induce an immunosuppressive microenvironment which leads towards
      tumor immune escape. Understanding the intricacy of immunomodulation by tumor
      cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an
      immunosuppressive enzyme which mediates tumor immune escape in various cancers
      including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to
      recruitment of regulatory T-cells into tumor microenvironment and therefore
      inhibit local immune responses and promote metastasis. HCC associated fibroblasts
      stimulate natural killer cells dysfunction through prostaglandin E2 and
      subsequently IDO promotes favorable condition for tumor metastasis. IDO up
      regulation induces immunosuppression and may enhance the risk of hepatitis C
      virus and hepatitis B virus induced HCC. Therefore, IDO inhibitors as adjuvant
      therapeutic agents may have clinical implications in HCC. This review proposes
      future prospects of IDO not only as a therapeutic target but also as a prognostic
      marker for HCC.

PMID- 28428709
TI  - Disruption of the TWEAK/Fn14 pathway prevents 5-fluorouracil-induced diarrhea in
      mice.
AB  - AIM: To clarify the roles of TWEAK and its receptor Fn14 in 5-fluorouracil (5-FU)
      induced diarrhea. METHODS: Diarrhea was induced in wild-type (WT), Fn14 knockout
      (KO), and IL-13 receptor (IL-13R)alpha1 KO BALB/c mice using a single injection
      of 5-FU. Histological analysis, cytokine analysis, and flow cytometry was
      performed on ileal tissues and cells. Murine colon carcinoma-bearing mice were co
      treated with an anti-TWEAK antibody and 5-FU. Embryonic fibroblast response to
      cytokines was also analyzed. RESULTS: 5-FU induced high Fn14 expression in
      epithelial cells. The severity of 5-FU-induced diarrhea was lower in Fn14 KO mice
      compared with WT mice. Administration of anti-TWEAK antibody reduced 5-FU-induced
      diarrhea without affecting the antitumor effects of 5-FU in vivo. 5-FU-induced
      expression of IL-13, IL-17A, TNF-alpha, and IFN-gamma in the ileum was Fn14
      dependent. The severity of 5-FU-induced diarrhea was lower in IL-13Ralpha1 KO
      mice, indicating major role for IL-13 signaling via IL-13Ralpha1 in pathogenesis.
      We found that IL-13Ralpha2, an IL-13 neutralizing/cell protective receptor, was
      strongly induced by IL-33 in vitro and in vivo. IL-13Ralpha2 was upregulated in
      the ileum of 5-FU-treated Fn14 KO mice. Thus, the deletion of Fn14 upregulated IL
      13Ralpha2 expression, which reduced IL-13 expression and activity. CONCLUSION:
      Disruption of the TWEAK/Fn14 pathway affects several interconnected pathways,
      including those associated with IL-13, IL-33, and IL-13Ralpha2, to attenuate 5-FU
      induced intestinal side effects.

PMID- 28428710
TI  - CMA down-regulates p53 expression through degradation of HMGB1 protein to inhibit
      irradiation-triggered apoptosis in hepatocellular carcinoma.
AB  - AIM: To investigate the mechanism of chaperone-mediated autophagy (CMA)-induced
      resistance to irradiation-triggered apoptosis through regulation of the p53
      protein in hepatocellular carcinoma (HCC). METHODS: Firstly, we detected
      expression of lysosome-associated membrane protein 2a (Lamp-2a), which is the key
      protein of CMA, by western blot in HepG2 and SMMC7721 cells after irradiation. We
      further used shRNA Lamp-2a HCC cells to verify the radioresistance induced by
      CMA. Next, we detected the HMGB1 and p53 expression after irradiation by western
      blot, and we further used RNA interference and ethyl pyruvate (EP), as a HMGB1
      inhibitor, to observe changes of p53 expression. Finally, an immunoprecipitation
      assay was conducted to explore the interaction between Lamp-2a and HMGB1, and the
      data were analyzed. RESULTS: We found the expression of Lamp-2a was increased on
      irradiation while apoptosis decreased in HepG2 and SMMC7721 cells. The apoptosis
      was increased markedly in the shRNA Lamp-2a HepG2 and SMMC7721 cells as detected
      by western blot and colony formation assay. Next, we found p53 expression was
      gradually reduced on irradiation but obviously increased in shRNA Lamp-2a cells.
      Furthermore, p53 increased the cell apoptosis on irradiation in Hep3B (p53-/-)
      cells. Finally, p53 levels were regulated by HMGB1 as measured through RNA
      interference and the EP treatment. HMGB1 was able to combine with Lamp-2a as seen
      by immunoprecipitation assay and was degraded via the CMA pathway. The decreased
      HMGB1 inhibited p53 expression induced by irradiation and further reduced the
      apoptosis in HCC cells. CONCLUSION: CMA pathway activation appears to down
      regulate the susceptibility of HCC to irradiation by degrading HMGB1 with further
      impact on p53 expression. These findings have clinical relevance for radiotherapy
      of HCC.

PMID- 28428711
TI  - Cullin 4A is associated with epithelial to mesenchymal transition and poor
      prognosis in perihilar cholangiocarcinoma.
AB  - AIM: To explore the functional role of cullin 4A (CUL4A), a core subunit of E3
      ubiquitin ligase, in perihilar cholangiocarcinoma (PHCC). METHODS: The expression
      of CUL4A in PHCC cell lines was evaluated by Western blot and quantitative
      reverse transcription-polymerase chain reaction. Immunohistochemistry (IHC) was
      adopted to investigate the relationship between CUL4A expression and
      clinicopathological characteristics of PHCC. Univariate analysis and multivariate
      regression analysis were performed to analyze the risk factors related to overall
      survival (OS) and progression-free survival (PFS) of PHCC patients. Wound
      healing, Transwell and Matrigel assays were utilized to explore the function of
      CUL4A in PHCC metastasis. Furthermore, expression of epithelial to mesenchymal
      transition (EMT) markers was verified in cells with CUL4A knockdown or
      overexpression. The relationship between CUL4A expression and E-cadherin
      expression was also analyzed by IHC assay. Finally, the role of ZEB1 in
      regulating CUL4A mediated PHCC was detected by IHC, Western blot, Transwell and
      Matrigel assays. RESULTS: CUL4A overexpression was detected in PHCC cell lines
      and clinical specimens. Clinicopathological analysis revealed a close correlation
      between CUL4A overexpression and tumour differentiation, T, N and TNM stages in
      PHCC. Kaplan-Meier analysis revealed that high CUL4A expression was correlated
      with poor OS and PFS of PHCC patients. Univariate analysis identified the
      following four parameters as risk factors related to OS rate of PHCC: T, N, TNM
      stages and high CUL4A expression; as well as three related to PFS: N stage, TNM
      stage and high CUL4A expression. Further multivariate logistic regression
      analysis identified high CUL4A expression as the only independent prognostic
      factor for PHCC. Moreover, CUL4A silencing in PHCC cell lines dramatically
      inhibited metastasis and the EMT. Conversely, CUL4A overexpression promoted these
      processes. Mechanistically, ZEB1 was discovered to regulate the function of CUL4A
      in promoting the EMT and metastasis. CONCLUSION: CUL4A is an independent
      prognostic factor for PHCC, and it can promote the EMT by regulating ZEB1
      expression. CUL4A may be a potential therapeutic target for PHCC.

PMID- 28428712
TI  - Notch signaling mediated by TGF-beta/Smad pathway in concanavalin A-induced liver
      fibrosis in rats.
AB  - AIM: To explore the exact interaction between Notch and transforming growth
      factor (TGF)-beta signaling in liver fibrosis. METHODS: We established a rat
      model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear
      cells (PBMCs) were isolated from the modeled rats, and cultured with gamma
      secretase inhibitor DAPT and TGF-beta inhibitor for 24 h. The mRNA levels of
      Notch and TGF-beta signaling were detected by quantitative real-time polymerase
      chain reaction. Expression of Notch and TGF-beta proteins was analyzed by western
      blotting. RESULTS: Compared to control rats, Notch and TGF-beta signaling was
      activated in PBMCs of model rats. Administration of DAPT and TGF-beta inhibitor
      suppressed Notch and TGF-beta signal transducer in PBMCs of model rats. DAPT
      reduced mRNA and protein expression of TGF-beta signaling, such as TGF-beta1 and
      Smad3. TGF-beta inhibitor also downregulated Notch1, Hes1 and Hes5, and mRNA and
      protein expression of the Notch signaling pathway. CONCLUSION: Notch and TGF-beta
      signaling play a role in liver fibrosis. TGF-beta signaling upregulates Notch
      signaling, which promotes TGF-beta signaling.

PMID- 28428713
TI  - MicroRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by
      targeting CD44 in gastric cancer.
AB  - AIM: To determine the potential roles of CD4 and microRNA (miR)-145 in gastric
      cancer. METHODS: The levels of CD44 and miR-145 were determined in gastric cancer
      cells. Quantitative real-time polymerase chain reaction was used to measure to
      the level of CD44 mRNA. A luciferase reporter assay and western blotting were
      performed to examine the effect of miR-145 on CD44 expression. Tumor sphere and
      MTT assays were carried out to evaluate the self-renewal and chemo-resistance
      properties of gastric cancer cells. RESULTS: The expression of CD44 was greatly
      increased and miR-145 was decreased in gastric cancer cells that were highly
      enriched in cancer stem cells (CSCs). The results demonstrated that miR-145
      regulated CD44 by targeting directly the CD44 3'-untranslated region (3'-UTR). In
      gastric cancer cells, overexpression of miR-145 repressed the activity of the
      CD44 3'-UTR, and disruption of miR-145/CD44 3'-UTR interactions abrogated the
      silencing effects. In addition, miR-145 inhibition stimulated CD44 3'-UTR
      activity and disruption of miR-145/CD44 3'-UTR interactions abrogated this
      stimulatory effect. Enforced CD44 expression greatly increased tumor sphere
      formation and chemo-resistance in gastric cancer cells. Furthermore, the
      inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with
      miR-145 were significantly abrogated by overexpression of CD44. CONCLUSION: miR
      145 targeting of CD44 plays critical roles in the regulation of tumor growth and
      chemo-resistance in gastric cancer.

PMID- 28428714
TI  - Predictors for difficult cecal insertion in colonoscopy: The impact of obesity
      indices.
AB  - AIM: To identify the factors influencing cecal insertion time (CIT) and to
      evaluate the effect of obesity indices on CIT. METHODS: We retrospectively
      reviewed the data for participants who received both colonoscopy and abdominal
      computed tomography (CT) from February 2008 to May 2008 as part of a
      comprehensive health screening program. Age, gender, obesity indices [body mass
      index (BMI), waist-to-hip circumference ratio (WHR), waist circumference (WC),
      visceral adipose tissue (VAT) volume and subcutaneous adipose tissue (SAT) volume
      on abdominal CT], history of prior abdominal surgery, constipation, experience of
      the colonoscopist, quality of bowel preparation, diverticulosis and time required
      to reach the cecum were analyzed. CIT was categorized as longer than 10 min
      (prolonged CIT) and shorter than or equal to 10 min, and then the factors that
      required a CIT longer than 10 min were examined. RESULTS: A total of 1678
      participants were enrolled. The mean age was 50.42 +/- 9.931 years and 60.3% were
      men. The mean BMI, WHR, WC, VAT volume and SAT volume were 23.92 +/- 2.964 kg/m2,
      0.90 +/- 0.076, 86.95 +/- 8.030 cm, 905.29 +/- 475.220 cm3 and 1707.72 +/-
      576.550 cm3, respectively. The number of patients who underwent abdominal surgery
      was 268 (16.0%). Colonoscopy was performed by an attending physician alone in
      61.9% of cases and with the involvement of a fellow in 38.1% of cases. The median
      CIT was 7 min (range 2-56 min, IQR 5-10 min), and mean CIT was 8.58 +/- 5.291
      min. Being female, BMI, VAT volume and involvement of fellow were significantly
      associated with a prolonged CIT in univariable analysis. In multivariable
      analysis, being female (OR = 1.29, P = 0.047), lower BMI (< 23 kg/m2) (OR = 1.62,
      P = 0.004) or higher BMI (>= 25 kg/m2) (OR = 1.80, P < 0.001), low VAT volume (<
      500 cm3) (OR = 1.50, P = 0.013) and fellow involvement (OR = 1.73, P < 0.001)
      were significant predictors of prolonged CIT. In subgroup analyses for gender,
      lower BMI or higher BMI and fellow involvement were predictors for prolonged CIT
      in both genders. However, low VAT volume was associated with prolonged CIT in
      only women (OR = 1.54, P = 0.034). CONCLUSION: Being female, having a lower or
      higher BMI than the normal range, a low VAT volume, and fellow involvement were
      predictors of a longer CIT.

PMID- 28428715
TI  - Impact of interferon-free antivirus therapy on lipid profiles in patients with
      chronic hepatitis C genotype 1b.
AB  - AIM: To investigate the influence of interferon-free antivirus therapy on lipid
      profiles in chronic hepatitis C virus genotype 1b (HCV1b) infection. METHODS:
      Interferon-free antiviral agents were used to treat 276 patients with chronic
      HCV1b infection, and changes in serum lipids of those who achieved sustained
      virologic response (SVR) were examined. The treatment regimen included 24 wk of
      daclatasvir plus asunaprevir (DCV + ASV) or 12 wk of sofosbuvir plus ledipasvir
      (SOF + LDV). SVR was achieved in 121 (85.8%) of 141 patients treated with DCV +
      ASV and 132 (97.8%) of 135 patients treated with SOF + LDV. In the two patient
      groups (DCV + ASV-SVR and SOF + LDV-SVR), serum total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), and triglycerides were measured at baseline during treatment and at 4
      and 12 wk after treatment. Then, longitudinal changes in lipid profiles were
      analyzed. RESULTS: Serum levels of TC, LDL-C, and HDL-C were significantly
      increased throughout the observation period in both the DCV + ASV-SVR and SOF +
      LDV-SVR groups. During antivirus treatment, the increases in TC and LDL-C were
      significantly greater in the SOF + LDV-SVR group than in the DCV + ASV-SVR group
      (P < 0.001). At 4 and 12 wk after the therapy, serum levels of TC and LDL-C were
      similar between the two groups and were significantly greater than those at
      baseline. Approximately 75%-80% of the increase in TC was derived from an
      increased LDL-C. In multiple regression analysis, the difference in therapy
      protocol (DCA + ASV or SOF + LDV) was an independent predictor that was
      significantly associated with the increase in TC and LDL-C at 4 wk of therapy.
      CONCLUSION: Serum cholesterol significantly increased during SOF + LDV treatment.
      After treatment, HCV elimination was associated with a similar increase in
      cholesterol regardless of the therapy protocol.

PMID- 28428716
TI  - Transition after pediatric liver transplantation - Perceptions of adults,
      adolescents and parents.
AB  - AIM: To develop a locally adapted, patient-focused transition-program, we
      evaluated the perceptions of adult and adolescent patients and parents regarding
      transition-programs and transfer. METHODS: We evaluated these perceptions by
      analyzing the responses of pre-transfer adolescents (n = 57), their parents (n =
      57) and post-transfer adults (n = 138) from a cohort of pediatric-liver
      transplant-patients using a self-designed questionnaire. Furthermore, we compared
      a responder group with a non-responder group as well as the provided answers with
      baseline characteristics and clinical outcomes to exclude selection bias,
      characterize high-risk patients for non-adherence and test for gender
      differences. Included in our study were all pre-transfer liver transplant and
      combined liver-kidney transplant recipients aged 11-19 currently under our care
      and their parents, as well as all post-transfer liver transplant and combined
      liver-kidney transplant recipients aged >= 17 years who had received a liver
      transplant and were treated at our center during childhood. RESULTS: Fifty-seven
      (24 female) pre-transfer patients who received a transplant in the previous 8-186
      mo (mean 93.9 mo, median 92 mo, SD 53.8 mo) and 138 (57 female) post-transfer
      patients who received a transplant in the preceding 2-29 years (mean 15.6 years,
      median 17, SD 6.90) met the inclusion criteria. A total of 67% of pre-transfer
      patients (71% of female; 64% of male; P = 0.78) and their parents replied.
      Additionally, 54% of post-transfer patients (26% of female; 48% of male; P =
      0.01) replied. No differences in clinical outcomes were observed between the
      responder and non-responder groups, and responses did not differ significantly
      based on clinical complication rates, although they did differ based on gender
      and the location of medical follow-up after transfer. Adolescents were generally
      ambivalent toward transition programs. However, adults strongly supported
      transition programs. CONCLUSION: Transition programs need to be developed in
      close collaboration with adolescents. The best clinical practices regarding
      transition should respect local circumstances, gender and the location of post
      transfer medical follow-up.

PMID- 28428717
TI  - Minimally invasive surgery for gastric cancer: A comparison between robotic,
      laparoscopic and open surgery.
AB  - AIM: To investigate the role of minimally invasive surgery for gastric cancer and
      determine surgical, clinical, and oncological outcomes. METHODS: This is a
      propensity score-matched case-control study, comparing three treatment arms:
      robotic gastrectomy (RG), laparoscopic gastrectomy (LG), open gastrectomy (OG).
      Data collection started after sharing a specific study protocol. Data were
      recorded through a tailored and protected web-based system. Primary outcomes:
      harvested lymph nodes, estimated blood loss, hospital stay, complications rate.
      Among the secondary outcomes, there are: operative time, R0 resections, POD of
      mobilization, POD of starting liquid diet and soft solid diet. The analysis
      includes the evaluation of type and grade of postoperative complications.
      Detailed information of anastomotic leakages is also provided. RESULTS: The
      present analysis was carried out of 1026 gastrectomies. To guarantee homogenous
      distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched
      using a propensity score analysis with a caliper = 0.2. The successful matching
      resulted in a total sample of 604 patients (RG = 151; LG = 151; OG = 302). The
      three groups showed no differences in all baseline patients characteristics, type
      of surgery (P = 0.42) and stage of the disease (P = 0.16). Intraoperative blood
      loss was significantly lower in the LG (95.93 +/- 119.22) and RG (117.91 +/-
      68.11) groups compared to the OG (127.26 +/- 79.50, P = 0.002). The mean number
      of retrieved lymph nodes was similar between the RG (27.78 +/- 11.45), LG (24.58
      +/- 13.56) and OG (25.82 +/- 12.07) approach. A benefit in favor of the minimally
      invasive approaches was found in the length of hospital stay (P < 0.0001). A
      similar complications rate was found (P = 0.13). The leakage rate was not
      different (P = 0.78) between groups. CONCLUSION: Laparoscopic and robotic surgery
      can be safely performed and proposed as possible alternative to open surgery. The
      main highlighted benefit is a faster postoperative functional recovery.

PMID- 28428718
TI  - Clinical implication of FDG uptake of bone marrow on PET/CT in gastric cancer
      patients with surgical resection.
AB  - AIM: To determine the relationship between F-18 fluorodeoxyglucose (FDG) uptake
      of bone marrow (BM) on positron emission tomography/computed tomography (PET/CT)
      and clinical factors and to assess the prognostic value of FDG uptake of BM in
      gastric carcinoma. METHODS: We retrospectively enrolled 309 gastric cancer
      patients who underwent staging FDG PET/CT and curative surgical resection. FDG
      uptake of primary tumor was visually classified as positive or negative FDG
      uptake. Mean FDG uptake of BM (BM SUV) and BM-to-liver uptake ratio (BLR) were
      measured. The relationships of BM SUV or BLR with clinical factors were
      evaluated. The prognostic values of BM SUV, BLR, and other clinical factors for
      predicting recurrence-free survival (RFS) and overall survival (OS) were
      assessed. RESULTS: Of 309 patients, 38 patients (12.3%) experienced cancer
      recurrence and 18 patients (5.8%) died. Patients with advanced gastric cancer,
      positive FDG uptake, and recurrence had higher values of BM SUV and BLR than
      those with early gastric cancer, negative FDG uptake, and no recurrence (P <
      0.05). BM SUV and BLR were significantly correlated with hemoglobin level,
      neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (P < 0.05). On
      multivariate analysis, multiple tumors, T stage, lymph node metastasis, tumor
      involvement of resection margin, and BLR were significantly associated with RFS
      (P < 0.05). T stage, lymph node metastasis, hemoglobin level, and BLR were
      significantly associated with OS (P < 0.05). CONCLUSION: BLR on PET/CT was an
      independent prognostic factor for RFS and OS in gastric cancer patients with
      curative surgical resection.

PMID- 28428719
TI  - Safety and efficacy of tenofovir in chronic hepatitis B-related decompensated
      cirrhosis.
AB  - AIM: To evaluate the safety and efficacy of tenofovir disoproxil fumarate (TDF)
      as a first-line therapy in decompensated liver disease. METHODS: We enrolled 174
      chronic hepatitis B-related liver cirrhosis patients treated with 300 mg/d TDF at
      six Korean centers. Of the 174 cirrhosis patients, 57 were assigned to the
      decompensated cirrhosis group and 117 were assigned to the compensated cirrhosis
      group. We followed the patients for 12 mo and evaluated clinical outcomes,
      including biochemical, virological, and serological responses. We also evaluated
      changes in hepatic and renal function and compared the decompensated and
      compensated cirrhosis groups. RESULTS: The 1-year complete virological response
      (CVR) and Hepatitis B e antigen (HBeAg) seroconversion were seen in 70.2% and
      14.2% in the decompensated cirrhosis group, respectively. The rates of HBeAg
      seroconversion/loss and ALT normalization at month 12 were similar in both
      groups. TDF treatment was also effective for decreasing the level of hepatitis B
      virus (HBV) DNA in both groups, but CVR was higher in the compensated group
      (88.9% vs 70.2%, P = 0.005). Tenofovir treatment for 12 mo resulted in improved
      Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores in
      decompensated group (P < 0.001). Of the 57 decompensated patients, 39 (68.4%)
      achieved CTP class A and 27 (49.1%) showed improvement in the CTP score of 2
      points after 12 mo of TDF. The observed rate of confirmed 0.5 mg/dL increases in
      serum levels of creatinine in the decompensated and compensated cirrhosis group
      were 7.0% and 2.5%, respectively (P < 1.000). CONCLUSION: TDF therapy in
      decompensated cirrhosis patients was effective for decreasing HBV DNA levels and
      improving hepatic function with relatively lower CVR than in compensated
      cirrhosis. Thus, physicians should carefully monitor not only renal function but
      also treatment responses when using TDF in decompensated cirrhosis patients.

PMID- 28428720
TI  - Can mean platelet volume play a role in evaluating the severity of acute
      pancreatitis?
AB  - AIM: To investigate serum mean platelet volume (MPV) levels in acute pancreatitis
      (AP) patients and assess whether MPV effectively predicts the disease severity of
      AP. METHODS: We included 117 consecutive patients with AP as the AP group and 34
      consecutive patients with colorectal polyps (before endoscopic treatment) as the
      control group. Complete blood counts, liver function, platelet indices (MPV),
      coagulation parameters, lactate dehydrogenase (LDH) and C-reactive protein (CRP)
      were measured on days 1, 2, 3 and 7 after admission. Receiver operating
      characteristic curves were used to compare the sensitivity and specificity of
      MPV, white blood cell (WBC), LDH and CRP in predicting AP severity. The Modified
      Glasgow Prognostic Score (mGPS) and the 2012 revised Atlanta criteria were used
      to evaluate disease severity in AP. RESULTS: MPV levels were significantly lower
      in the AP group than in the control group on day 1 (P = 0.000), day 2 (P = 0.029)
      and day 3 (P = 0.001) after admission. In addition, MPV values were lower on day
      1 after admission than on day 2 (P = 0.012), day 3 (P = 0.000) and day 7 (P =
      0.002) in all AP patients. Based on the mGPS, 78 patients (66.7%) were diagnosed
      with mild and 39 patients (33.3%) with severe AP. There was no significant
      difference in mean MPV levels between patients diagnosed with mild and severe AP
      based on the mGPS (P = 0.424). According to the 2012 revised Atlanta criteria,
      there were 98 patients (83.8%) without persistent organ failure (OF) [non-severe
      acute pancreatitis (non-SAP) group] and 19 patients (16.2%) with persistent OF
      (SAP group). MPV levels were significantly lower in the SAP group than in the non
      SAP group on day 1 after admission (P = 0.002). On day 1 after admission using a
      cut-off value of 6.65 fL, the overall accuracy of MPV for predicting SAP
      according to the 2012 revised Atlanta criteria (AUC = 0.716) had a sensitivity of
      91.8% and a specificity of 47.4% and was superior to the accuracy of the
      traditional markers WBC (AUC = 0.700) and LDH (AUC = 0.697). CONCLUSION: MPV can
      be used at no additional cost as a useful, non-invasive biomarker that
      distinguishes AP with persistent OF from AP without persistent OF on day 1 of
      hospital admission.

PMID- 28428721
TI  - Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal
      disorders of the esophagus, including eosinophilic esophageal myositis.
AB  - AIM: To define clinical criteria to differentiate eosinophilic gastrointestinal
      disorder (EoGD) in the esophagus. METHODS: Our criteria were defined based on the
      analyses of the clinical presentation of eosinophilic esophagitis (EoE),
      subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal
      myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E
      levels (s-IgE), in combination with histological and polymerase chain reaction
      analyses on esophageal tissue samples. RESULTS: In five patients with EoE,
      endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings
      in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal
      compression only. Using manometry, failed peristalsis was observed in patients
      with EoE and sEoE with some variation, while EoEM was associated with
      hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology
      revealed the following eosinophils per high-power field values. EoE = 41.4 +/-
      7.9 in the epithelium and 2.3 +/- 1.5 in the subepithelium; sEoE = 3 in the
      epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the
      epithelium, 10.7 +/- 11.7 in the subepithelium (conventional biopsy or endoscopic
      mucosal resection) and 46.8 +/- 16.5 in the muscularis propria (peroral
      esophageal muscle biopsy). Presence of dilated epithelial intercellular space and
      downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were
      overexpressed in EoE. CONCLUSION: Based on clinical and histological data, we
      identified criteria, which differentiated between EoE, sEoE and EoEM, and
      reflected a different pathogenesis between these esophageal EoGDs.

PMID- 28428722
TI  - Therapeutic experience of 289 elderly patients with biliary diseases.
AB  - AIM: To present clinical characteristics, diagnosis and treatment strategies in
      elderly patients with biliary diseases. METHODS: A total of 289 elderly patients
      with biliary diseases were enrolled in this study. The clinical data relating to
      these patients were collected in our hospital from June 2013 to May 2016. Patient
      age, disease type, coexisting diseases, laboratory examinations, surgical
      methods, postoperative complications and therapeutic outcomes were analyzed.
      RESULTS: The average age of the 289 patients with biliary diseases was 73.9 +/-
      8.5 years (range, 60-102 years). One hundred and thirty-one patients (45.3%) had
      one of 10 different biliary diseases, such as gallbladder stones, common bile
      duct stones, and cholangiocarcinoma. The remaining patients (54.7%) had two types
      of biliary diseases. One hundred and seventy-nine patients underwent 9 different
      surgical treatments, including pancreaticoduodenectomy, radical resection of
      hilar cholangiocarcinoma and laparoscopic cholecystectomy. Ten postoperative
      complications occurred with an incidence of 39.3% (68/173), and hypopotassemia
      showed the highest incidence (33.8%, 23/68). One hundred and sixteen patients
      underwent non-surgical treatments, including anti-infection, symptomatic and
      supportive treatments. The cure rate was 97.1% (168/173) in the surgical group
      and 87.1% (101/116) in the non-surgical group. The difference between these two
      groups was statistically significant (chi2 = 17.227, P < 0.05). CONCLUSION:
      Active treatment of coexisting diseases, management of indications and surgical
      opportunities, appropriate selection of surgical procedures, improvements in
      perioperative therapy, and timely management of postoperative complications are
      key factors in enhancing therapeutic efficacy in elderly patients with biliary
      diseases.

PMID- 28428724
TI  - Hepatic angiosarcoma with clinical and histological features of Kasabach-Merritt
      syndrome.
AB  - Hepatic angiosarcoma is a mesenchymal tumor originating from liver sinusoidal
      endothelial cells. It is an extremely rare malignant neoplasm accounting for less
      than 1% of primary malignant liver tumors. The deregulated coagulopathy that can
      be seen in hepatic angiosarcoma fulfills the clinical diagnostic criteria of
      disseminated intravascular coagulation. However, the mechanism that governs this
      coagulopathy has been poorly understood. This case report provides histological
      evidence of the consumption of coagulation factors along with trapped platelets
      occurring within the tumor, which is the foundation for the concept of Kasabach
      Merritt syndrome (KMS). KMS is characterized by thrombocytopenia and
      hyperconsumption of coagulation factors within a vascular tumor. However, KMS
      associated with angiosarcoma has not been well recognized. This case report
      describes, for the first time, the histological evidence of KMS that occurred in
      an extremely rare mesenchymal malignant tumor of the liver.

PMID- 28428723
TI  - What is the quantitative risk of gastric cancer in the first-degree relatives of
      patients? A meta-analysis.
AB  - AIM: To quantify the risk of gastric cancer in first-degree relatives of patients
      with the cancer. METHODS: A comprehensive literature search was performed. Case
      control trials comparing the frequency of a positive family history of gastric
      cancer in patients with gastric cancer, vs non-gastric cancer controls were
      retrieved. Studies with missed or non-extractable data, studies in children,
      abstracts, and duplicate publications were excluded. A meta-analysis of pooled
      odd ratios was performed using Review Manager 5.0.25. We performed subgroup
      analysis on Asian studies and a sensitivity analysis based on the quality of the
      studies, type of the outcome, sample size, and whether studies considered only
      first-degree relatives. RESULTS: Thirty-two relevant studies out of 612 potential
      abstracts (n = 80690 individuals) were included. 19.0% of the patients and 10.9%
      of the controls had at least one relative with gastric cancer (P < 0.00001). The
      pooled relative risk for the development of gastric cancer in association with a
      positive family history was 2.35 (95%CI: 1.96-2.81). The Cochran Q test for
      heterogeneity was positive (P < 0.00001, I2 = 92%). After excluding the three
      outlier studies with the highest relative risks, heterogeneity remained
      significant (P < 0.00001, I2 = 90%). The result was not different among Asian
      studies as compared to others and remained robust in several sensitivity
      analyses. In the 26 studies which exclusively analysed the history of gastric
      cancer in first-degree relatives, the relative risk was 2.71 (95%CI: 2.08-3.53; P
      < 0.00001). CONCLUSION: Individuals with a first-degree relative affected with
      gastric cancer have a risk of about 2.5-fold for the development of gastric
      cancer. This could be due to genetic or environmental factors. Screening and
      preventive strategies should be developed for this high-risk population.

PMID- 28428725
TI  - Tumor biopsy and patient enrollment in clinical trials for advanced
      hepatocellular carcinoma.
AB  - Tumor biopsies may help to reliably distinguish hepatocellular carcinoma (HCC)
      from other tumors, mostly cholangiocarcinoma as well as to identify the patient
      populations who most benefit from target-driven HCC treatments, in order to
      improve the success rate of experimental therapies. Clarifying tumor biology may
      also lead to identify biomarkers with prognostic role and/or enabling to predict
      response or resistance to therapies. Recently, clinical trials have more
      efficiently included biomarker endpoints and increasingly collected tumor tissue
      from enrolled patients. Due to their frail status and sometimes fast-progressing
      disease, the performance status of patients with HCC progressing on first-line
      therapy can deteriorate quickly, preventing their enrollment in clinical trials.
      However, the challenge of identifying the proper patient at the proper time can
      be overcome by periodic inter-department meetings involving the key specialists
      taking care of HCC patients, and solid networks between research centers and
      referring institutions. An early planned biopsy would also facilitate timely
      inclusion of patients in biology-driven clinical trials. Ultimately, institution
      of multidisciplinary teams can optimize treatment choice, biopsy timing, and
      quick enrollment of patients in clinical trials, before their performance status
      deteriorates.

PMID- 28428726
TI  - Successful Treatment of Prosthetic Joint Infection due to Vancomycin-resistant
      Enterococci with Tedizolid.
AB  - Few antibiotic options exist for the management of infections due to vancomycin
      resistant enterococci (VRE). We describe a case involving the safe and successful
      use of tedizolid, a new oxazolidinone, to treat VRE prosthetic joint infection.

PMID- 28428727
TI  - Improved methods for evaluating the environmental impact of nanoparticle
      synthesis?.
AB  - With the market for products containing nanoparticles growing, improvements in
      the efficiency of nanoparticle synthesis are poised to have significant positive
      economic and environmental impacts. While many metrics have been designed for
      measuring the efficiency of small molecule synthesis, the use of these metrics
      for evaluating nanoparticle preparation has not been optimized. Here a critical
      evaluation of various green chemistry metrics is provided as they are applied to
      a common set of nanoparticle synthetic methods. The effect of the nanoparticle
      polydispersity on the relative greenness of different synthetic methods is also
      examined. Using metrics modified to account for polydispersity, a case study of
      gold nanoparticle syntheses is provided and three different methods of preparing
      monodisperse gold nanoparticles are compared. Interestingly, not all of the
      metrics provide the same rankings for the synthetic methods. And when
      polydispersity is ignored, the metrics provide a different rank order of the
      methods, highlighting the importance of clearly defining the desired nanoparticle
      size range to avoid underestimating the environmental impact.

PMID- 28428728
TI  - Randomized Face-to-Face vs. Home Exercise Interventions in Pregnant Women with
      Gestational Diabetes.
AB  - OBJECTIVES: Evaluate effects of a theoretically-based, semi-intensive (Face-to
      Face; F2F) exercise intervention and minimum-contact (Home) exercise intervention
      to the standard care (Control) on exercise, its motivational determinants, blood
      glucose levels, and insulin use of pregnant women with gestational diabetes
      mellitus (GDM). DESIGN: Randomized control trial with two intervention arms and
      control (standard care). METHOD: Participants (N=65) were randomized to a Control
      (standard prenatal care/GDM dietary counseling), Home (standard care + phone
      education/support + home exercise), or F2F (standard care + on-site
      education/support + guided exercise with instructor on 2 days/week) group from
      ~20 weeks gestation to delivery. Assessments of exercise and motivational
      determinants were obtained at baseline (20-weeks gestation) and follow-up (32
      weeks gestation). Blood glucose levels (fasting/postprandial mg/dL) and insulin
      use were extrapolated from medical records. RESULTS: At the 32-week follow-up,
      the F2F group had significantly higher exercise min, pedometer steps/day, and
      motivational determinants (attitude, subjective norm, perceived control,
      intention) than controls (p's < .05) and significantly higher exercise min and
      subjective norm than the Home group (p's < .05); these effect sizes were medium
      large (eta2 = .11-.23). There was a medium effect (eta2 = .13) on postprandial
      blood glucose at 36-weeks gestation with the F2F group having lower values than
      controls. Although not significant, the F2F group started insulin later (33 weeks
      gestation) than the Home (27 weeks) and Control (31 weeks) groups. CONCLUSION: A
      theoretically-based, F2F exercise intervention has multiple health benefits and
      may be the necessary approach for promoting exercise motivation and behavior
      among GDM women.

PMID- 28428730
TI  - The Tele.TAnDem intervention: study protocol for a psychotherapeutic intervention
      for family caregivers of people with dementia.
AB  - BACKGROUND: Family caregivers are confronted with high demands creating a need
      for professional support and at the same time hindering its utilization.
      Telephone support allows easier access than face-to-face support because there is
      no need to leave the person with dementia alone or find an alternative carer. It
      is also independent of transport possibilities or mobility. The objectives are to
      evaluate whether telephone-based cognitive-behavioral therapy, which is
      implemented in established care provision structures, improves outcomes compared
      to usual care and whether it is as effective as face-to-face cognitive-behavioral
      therapy. METHODS/DESIGN: If participants live in the area of one of the study
      centers (Jena, Berlin, Munich) and indicate that attendance of a face-to-face
      therapy is possible, they will be assigned to the face-to-face group. The other
      participants will be randomized to receive either telephone-based cognitive
      behavioral therapy or usual care. Data will be collected at baseline, post
      intervention, and at a 6-month follow-up. The primary outcomes will be
      depressiveness, burden of care, health complaints, and problem-solving ability.
      The secondary outcomes will be anxiety, quality of life, violence in caregiving,
      utilization of professional assistance, and cost effectiveness. DISCUSSION: This
      paper describes the evaluation design of our telephone-based cognitive-behavioral
      therapy in a randomized controlled trial. If this intervention proves to be an
      effective tool to improve outcomes, it will be made accessible to the public and
      the use of this support service will be recommended. TRIAL REGISTRATION: German
      Clinical Trials Register DRKS00006355.

PMID- 28428729
TI  - The risk of bias in randomized controlled trials in otorhinolaryngology: hardly
      any improvement since 1950.
AB  - BACKGROUND: Randomized Controlled Trials (RCTs) represent the most valuable study
      design to evaluate the effectiveness of therapeutic interventions. However, flaws
      in design, conduct, analysis, and reporting of RCTs can cause the effect of an
      intervention to be under- or overestimated. These biased RCTs may be included in
      literature reviews. To make the assessment of Risk of Bias (RoB) consistent and
      transparent, Cochrane published a RoB tool, with which RoB is assessed per item
      as "low", "unclear" or "high". Our objective was to provide an overview of RoB
      assessments of RCTs in otorhinolaryngology over time, and to identify items where
      improvement is still warranted. METHODS: We retrieved Cochrane reviews in the
      otorhinolaryngologic research field published in 2012 and 2013. We used all
      judgments per item as assessed by the review authors of the included RCTs. We
      evaluated the association between "low RoB" vs. "unclear and high RoB" and the
      year of publication (time strata: '<1990', '1990-1995', '1996-2000', '2001-2005',
      '2006-2012') per item using binary logistic regression. RESULTS: We extracted the
      RoB assessments from 42 Cochrane reviews that had included 402 RCTs (median
      number of RCTs per review: 7, range 1-40). In total 2,356 items were assessed
      (mean number of assessed items per RCT: 5.9, standard deviation 1.8). On binary
      logistic regression, RCTs published in 2006-2012, compared with those published
      before 1990, were more likely to have a low RoB for two items: random sequence
      generation (odds ratio 6.09 [95% confidence interval: 3.11-11.95]) and allocation
      concealment (3.59 [1.87-6.90]). On all other items, there was no significant
      increase in the proportion of low RoB when comparing RCTs published in 2006-2012
      with RCTs published before 1990. CONCLUSION: Although there were some positive
      developments in the RoB assessments in otorhinolaryngology, a further decrease in
      RoB is still warranted on several items. Currently, biased RCTs are included in
      Cochrane reviews and effects of therapeutic interventions can be under- or
      overestimated, with implications for clinical patient care.

PMID- 28428731
TI  - Governing mobile technology use for continuing professional development in the
      Australian nursing profession.
AB  - BACKGROUND: The rapid growth in the use of mobile technology in Australia has
      outpaced its governance, especially in healthcare settings. Whilst some
      Australian professional bodies and organisations have developed standards and
      guidelines to direct appropriate use of social media and mobile technology, clear
      governance arrangements regarding when, where and how to use mobile technology at
      point of care in nursing are currently lacking. DISCUSSION: This paper analyses
      how the use of mobile technology by nurses at point of care is governed. It
      highlights the existence of a mobile technology paradox: an identified inability
      of nurses to access mobile technology in a context where it is increasingly
      recognised that its use in situ can enhance nursing practice while contributing
      to mobile learning and continuing professional development. While the recent
      release of the Registered Nurse Standards for Practice and accompanying Standard
      for Continuing Professional Development provides some direction regarding
      professional standards to support the use of mobile technology for mobile
      learning, we argue a more inclusive approach is required if emerging technologies
      are to be fully embraced. We describe how an implementation framework,
      underpinned by more detailed standards, guidelines and codes, could enable the
      nursing profession to be leaders in embedding mobile technology in healthcare
      environments nationally and globally. CONCLUSION: The prevalence of mobile
      technology in Australia has outpaced its governance in healthcare environments.
      Its limited availability at point of care is hindering nursing practice, mobile
      learning and continuing professional development. We discuss the emergence of
      mobile technology and impediments for its use by nurses in situ. We analyse the
      professional codes governing nursing, outlining potential reforms to enable
      implementation of mobile technology at point of care by nurses.

PMID- 28428732
TI  - Access to information and counselling - older cancer patients' self-report: a
      cross-sectional survey.
AB  - BACKGROUND: An increasingly older population, improved diagnostics and treatment
      increase the number of older cancer survivors, thus more than 60% of those
      affected by cancer are over the age of 65. Symptom relief and the prevention of
      functional impairment are important tasks for home care nursing, considering that
      patients can live a long time with their cancer disease and related side effects.
      The aim of this study was to investigate the extent to which cancer patients over
      the age of 65 reported access to information and counselling from home care
      nursing services, including those offered by the cancer coordinator. METHODS: A
      cross-sectional survey was used. The survey consisted of 174 cancer patients from
      two regions in Norway living at home (101 women; 66-92 years). The questionnaire
      contained questions of various sequences including information and advices given
      and data on access to and use of home health care services. The questions focused
      on the extent to which home health care services provided the following: 1)
      information about the disease and treatment, 2) information about consequences
      and complications of the cancer disease, 3) nutritional advice and 4) advice on
      physical activity. Demographic, clinical and organizational variables were used.
      SPSS program version 22 was employed to perform descriptive and inferential
      statistics including correlation and logistic regression analysis. For ethical
      reasons, patients who were dying, delirious or with presence of cognitive
      impairment (any kind of dementia) were excluded. RESULTS: The results showed that
      a majority (67-77%) of the respondents reported low levels of information and
      counselling offered. Low levels represents in this study medium, small and very
      small degree (Likert scale). Women, those above 85 years of age and patients with
      a gynecological or hematological cancer diagnosis experienced less access to
      information and counselling. Respondents facing availability of a cancer
      coordinator reported significantly higher access to information about the disease
      and treatment (p = 0.03), nutritional advice (p = 0.04) and advice on physical
      activity (p = 0.04) compared to those who only had contact with a home health
      care nurse or home health care assistant. CONCLUSIONS: The results indicated that
      the availability of a cancer coordinator facilitated personalized information and
      counselling for older cancer patients.

PMID- 28428733
TI  - MicroRNA-338-3p suppresses cell proliferation and induces apoptosis of non-small
      cell lung cancer by targeting sphingosine kinase 2.
AB  - BACKGROUND: Lung cancer is the major cause of cancer-related death worldwide, and
      80% patients of lung cancer are non-small-cell lung cancer (NSCLC) cases.
      MicroRNAs are important gene regulators with critical roles in diverse biological
      processes, including tumorigenesis. Studies indicate that sphingosine kinase 2
      (SphK2) promotes tumor progression in NSCLC, but how this occurs is unclear.
      Thus, we explored the effect of miR-338-3p targeting SphK2 on proliferation and
      apoptosis of NSCLC cells. METHODS: Expression of miR-338-3p and SphK2 in NSCLC
      A549 and H1299 cell lines was measured using qRT-PCR and Western blot. CCK-8 and
      colony formation assays were used to assess the effect of miR-338-3p on NSCLC
      cell line proliferation. Flow cytometry was used to study the effect of miR-338
      3p on NSCLC apoptosis. Luciferase reporter assay and Western blot were used to
      confirm targeting of SphK2 by miR-338-3p. Finally, in vivo tumorigenesis studies
      were used to demonstrate subcutaneous tumor growth. RESULTS: miR-338-3p
      expression in 34 NSCLC clinical samples was downregulated and this was correlated
      with TNM stage. miR-338-3p significantly suppressed proliferation and induced
      apoptosis of NSCLC A549 and H1299 cells in vitro. SphK2 was a direct target of
      miR-338-3p. Overexpression of miR-338-3p significantly inhibited SphK2 expression
      and reduced luciferase reporter activity containing the SphK2 3'-untranslated
      region (3'-UTR) through the first binding site. SphK2 lacking 3'-UTR restored the
      effects of miR-338-3p on cell proliferation inhibition. miR-338-3p significantly
      inhibited tumorigenicity of NSCLC A549 and H1299 cells in a nude mouse xenograft
      model. CONCLUSIONS: Collectively, miR-338-3p inhibited cell proliferation and
      induced apoptosis of NSCLC cells by targeting and down-regulating SphK2, and miR
      338-3p could inhibit NSCLC cells A549 and H1299 growth in vivo, suggesting a
      potential mechanism of NSCLC progression. Therapeutically, miR-338-3p may serve
      as a potential target in the treatment of human lung cancer.

PMID- 28428734
TI  - Defining a staged-based process for economic and financial evaluations of mHealth
      programs.
AB  - Mobile and wireless technology for health (mHealth) has the potential to improve
      health outcomes by addressing critical health systems constraints that impede
      coverage, utilization, and effectiveness of health services. To date, few mHealth
      programs have been implemented at scale and there remains a paucity of evidence
      on their effectiveness and value for money. This paper aims to improve
      understanding among mHealth program managers and key stakeholders of how to
      select methods for economic evaluation (comparative analysis for determining
      value for money) and financial evaluation (determination of the cost of
      implementing an intervention, estimation of costs for sustaining or expanding an
      intervention, and assessment of its affordability). We outline a 6 stage-based
      process for selecting and integrating economic and financial evaluation methods
      into the monitoring and evaluation of mHealth solutions including (1) defining
      the program strategy and linkages with key outcomes, (2) assessment of
      effectiveness, (3) full economic evaluation or partial evaluation, (4) sub-group
      analyses, (5) estimating resource requirements for expansion, (6) affordability
      assessment and identification of models for financial sustainability. While
      application of these stages optimally occurs linearly, finite resources, limited
      technical expertise, and the timing of evaluation initiation may impede this. We
      recommend that analysts prioritize economic and financial evaluation methods
      based on programmatic linkages with health outcomes; alignment with an mHealth
      solution's broader stage of maturity and stage of evaluation; overarching
      monitoring and evaluation activities; stakeholder evidence needs; time point of
      initiation; and available resources for evaluations.

PMID- 28428735
TI  - Multiplicative Multitask Feature Learning.
AB  - We investigate a general framework of multiplicative multitask feature learning
      which decomposes individual task's model parameters into a multiplication of two
      components. One of the components is used across all tasks and the other
      component is task-specific. Several previous methods can be proved to be special
      cases of our framework. We study the theoretical properties of this framework
      when different regularization conditions are applied to the two decomposed
      components. We prove that this framework is mathematically equivalent to the
      widely used multitask feature learning methods that are based on a joint
      regularization of all model parameters, but with a more general form of
      regularizers. Further, an analytical formula is derived for the across-task
      component as related to the task-specific component for all these regularizers,
      leading to a better understanding of the shrinkage effects of different
      regularizers. Study of this framework motivates new multitask learning
      algorithms. We propose two new learning formulations by varying the parameters in
      the proposed framework. An efficient blockwise coordinate descent algorithm is
      developed suitable for solving the entire family of formulations with rigorous
      convergence analysis. Simulation studies have identified the statistical
      properties of data that would be in favor of the new formulations. Extensive
      empirical studies on various classification and regression benchmark data sets
      have revealed the relative advantages of the two new formulations by comparing
      with the state of the art, which provides instructive insights into the feature
      learning problem with multiple tasks.

PMID- 28428736
TI  - Simple sugar supplementation abrogates exercise-induced increase in hepcidin in
      young men.
AB  - BACKGROUND: At present many young people experience too much body iron
      accumulation. The reason of this phenomenon is not clear. There is accumulating
      evidences that not proper diet and lack of exercise could be a main contributing
      factors. This investigation assessed the effects of a diet rich in simple sugars
      (glucose or fructose) on exercise-induced hepcidin which is hormone regulating
      iron metabolism. METHODS: A group of physically active young men completed an
      incremental exercise test before and after a 3-day diet supplemented with
      fructose (4 g/kg BM) or glucose (4 g/kg BM). After a 1-week break, they crossed
      over to the alternate mode for the subsequent 3-days period. Venous blood samples
      were collected before and after 1 h exercise and were analysed for serum
      hepcidin, IL-6, CRP, iron, and ferritin. The physiological response to exercise
      was also determined. RESULTS: The concentration of hepcidin increased 1 h after
      exercise for the baseline test (p < 0.05), whereas no changes in hepcidin were
      observed in men whose diet was supplemented with fructose or glucose. Blood IL-6
      increased significantly after exercise only in subjects supplemented with
      fructose. Changes in hepcidin did not correlate with shifts in serum IL-6.
      CONCLUSIONS: These data suggest that protective effects of exercise on excess
      iron accumulation in human body which is mediated by hepcidin can be abrogated by
      high sugar consumption which is typical for contemporary people.

PMID- 28428737
TI  - Reducing sexual risk behaviors: secondary analyses from a randomized controlled
      trial of a brief web-based alcohol intervention for underage, heavy episodic
      drinking college women.
AB  - BACKGROUND: Alcohol use and sexual risk behaviors (SRBs) are significant problems
      on college campuses. College women are at particularly high risk for negative
      consequences associated with sexually transmitted infections (STIs) and unwanted
      pregnancy. METHODS: The current study (n = 160) examined the effect of a brief,
      web-based alcohol intervention (n = 53) for college women on reducing SRBs
      compared to an assessment only control (n = 107) with a randomized controlled
      trial. Outcome measures included condom use assertiveness and number of vaginal
      sex partners and data were collected at baseline and three-month follow-up.
      RESULTS: Regression analyses revealed that the alcohol intervention was
      associated with higher levels of condom use assertiveness at a three-month follow
      up. Additionally, more alcohol use was associated with less condom use
      assertiveness for those with more significant sexual assault histories.
      CONCLUSIONS: These findings suggest that alcohol interventions may impact college
      women's beliefs but not behavior, and future interventions should more explicitly
      target both alcohol and sexual risk to decrease risky behaviors.

PMID- 28428738
TI  - Improved Localization of Seizure Onset Zones Using Spatiotemporal Constraints and
      Time-Varying Source Connectivity.
AB  - Presurgical evaluation of brain neural activity is commonly carried out in
      refractory epilepsy patients to delineate as accurately as possible the seizure
      onset zone (SOZ) before epilepsy surgery. In practice, any subjective
      interpretation of electroencephalographic (EEG) recordings is hindered mainly
      because of the highly stochastic behavior of the epileptic activity. We propose a
      new method for dynamic source connectivity analysis that aims to accurately
      localize the seizure onset zones by explicitly including temporal, spectral, and
      spatial information of the brain neural activity extracted from EEG recordings.
      In particular, we encode the source nonstationarities in three critical stages of
      processing: Inverse problem solution, estimation of the time courses extracted
      from the regions of interest, and connectivity assessment. With the aim to
      correctly encode all temporal dynamics of the seizure-related neural network, a
      directed functional connectivity measure is employed to quantify the information
      flow variations over the time window of interest. Obtained results on simulated
      and real EEG data confirm that the proposed approach improves the accuracy of SOZ
      localization.

PMID- 28428739
TI  - High Salt Intake Augments Excitability of PVN Neurons in Rats: Role of the
      Endoplasmic Reticulum Ca2+ Store.
AB  - High salt (HS) intake sensitizes central autonomic circuitry leading to
      sympathoexcitation. However, its underlying mechanisms are not fully understood.
      We hypothesized that inhibition of PVN endoplasmic reticulum (ER) Ca2+ store
      function would augment PVN neuronal excitability and sympathetic nerve activity
      (SNA). We further hypothesized that a 2% (NaCl) HS diet for 5 weeks would reduce
      ER Ca2+ store function and increase excitability of PVN neurons with axon
      projections to the rostral ventrolateral medulla (PVN-RVLM) identified by
      retrograde label. PVN microinjection of the ER Ca2+ ATPase inhibitor thapsigargin
      (TG) increased SNA and mean arterial pressure (MAP) in a dose-dependent manner in
      rats with a normal salt (NS) diet (0.4%NaCl). In contrast, sympathoexcitatory
      responses to PVN TG were significantly (p < 0.05) blunted in HS treated rats
      compared to NS treatment. In whole cell current-clamp recordings from PVN-RVLM
      neurons, graded current injections evoked graded increases in spike frequency.
      Maximum discharge was significantly augmented (p < 0.05) by HS diet compared to
      NS group. Bath application of TG (0.5 MUM) increased excitability of PVN-RVLM
      neurons in NS (p < 0.05), yet had no significant effect in HS rats. Our data
      indicate that HS intake augments excitability of PVN-RVLM neurons. Inhibition of
      the ER Ca2+-ATPase and depletion of Ca2+ store likely plays a role in increasing
      PVN neuronal excitability, which may underlie the mechanisms of
      sympathoexcitation in rats with chronic HS intake.

PMID- 28428741
TI  - Assessing Auditory Processing Deficits in Tinnitus and Hearing Impaired Patients
      with the Auditory Behavior Questionnaire.
AB  - Background and Purpose: Auditory processing disorders (APD), tinnitus and hearing
      loss (HL) are typical issues reported by patients in audiologic clinics. These
      auditory impairments can be concomitant or mutually excluding. APD are not
      necessarily accompanied by significant HL, whereas many adults exhibit peripheral
      HL and typical cognitive deficits often associated with APD. Since HL, tinnitus
      and APD affects to several parts of the ascending auditory pathway from the
      periphery to the auditory cortex, there could be some interrelationship between
      them. For instance, tinnitus has been reported to degrade the auditory
      localization capacity. Tinnitus is believed to be triggered by deafferentation of
      normal peripheral input to the central auditory system. This peripheral deficit
      can be accompanied by HL or not, since a type of permanent cochlear damage (thus
      deafferentation) without an elevation of hearing thresholds might persist.
      Therefore, a combined study of APD, tinnitus and HL on the same cohort of
      patients can be audiologically relevant and worthy. Methods: Statistical analysis
      is applied to a cohort of 305 patients attending an audiology clinic in Madrid
      (Spain). This group of patients is first categorized in four subgroups, namely,
      HLTG (with tinnitus and HL), NHLTG (with tinnitus and without HL), HLNTG (with HL
      but no tinnitus), and NHLNTG (neither tinnitus nor HL). The statistical variables
      include Age, Average Auditory Threshold (ATT), for assessing HL, Tinnitus
      Handicap Inventory (THI), for measuring tinnitus, and a new 25-item Auditory
      Behavior Questionnaire (ABQ), for scoring APD. Factor analysis is applied to
      arrange these items into 4 subscales. The internal consistency reliability of
      this ABQ is confirmed by calculating Cronbach's coefficients alpha. The test
      retest reliability is assessed by the intraclass correlation coefficients, ICC.
      Statistical techniques applied to the data set include descriptive analysis of
      variables and Spearman rank correlations (rho) between them. Results: Overall
      reliability of ABQ is confirmed by an alpha value of 0.89 and by an ICC of 0.91.
      Regarding the internal consistency reliability, the four subscales prove a fairly
      good consistency with alpha coefficients above 0.7. Average values of statistical
      variables show significantly lower age of patients with tinnitus and no HL, which
      can provide a cue of noise overexposure of this segment of population. These
      younger patients show also decreased ABQ and similar THI in comparison with
      patients in the other subgroups. A strong correlation (rho = 0.63) was found
      between AAT and Age for the HLNTG subgroup. For the HLTG subgroup, a moderate
      correlation (rho = 0.44) was found between ABQ and THI. Conclusion: The utilized
      questionnaire (ABQ), together with AAT and THI, can help to study comorbid
      hearing impairments in patients regularly attending an audiological clinic.

PMID- 28428742
TI  - A Set-Based Mixed Effect Model for Gene-Environment Interaction and Its
      Application to Neuroimaging Phenotypes.
AB  - Imaging genetics is an emerging field for the investigation of neuro-mechanisms
      linked to genetic variation. Although imaging genetics has recently shown great
      promise in understanding biological mechanisms for brain development and
      psychiatric disorders, studying the link between genetic variants and
      neuroimaging phenotypes remains statistically challenging due to the high
      dimensionality of both genetic and neuroimaging data. This becomes even more
      challenging when studying gene-environment interaction (G*E) on neuroimaging
      phenotypes. In this study, we proposed a set-based mixed effect model for gene
      environment interaction (MixGE) on neuroimaging phenotypes, such as structural
      volumes and tensor-based morphometry (TBM). MixGE incorporates both fixed and
      random effects of G*E to investigate homogeneous and heterogeneous contributions
      of multiple genetic variants and their interaction with environmental risks to
      phenotypes. We discuss the construction of score statistics for the terms
      associated with fixed and random effects of G*E to avoid direct parameter
      estimation in the MixGE model, which would greatly increase computational cost.
      We also describe how the score statistics can be combined into a single
      significance value to increase statistical power. We evaluated MixGE using
      simulated and real Alzheimer's Disease Neuroimaging Initiative (ADNI) data, and
      showed statistical power superior to other burden and variance component methods.
      We then demonstrated the use of MixGE for exploring the voxelwise effect of G*E
      on TBM, made feasible by the computational efficiency of MixGE. Through this, we
      discovered a potential interaction effect of gene ABCA7 and cardiovascular risk
      on local volume change of the right superior parietal cortex, which warrants
      further investigation.

PMID- 28428743
TI  - Editorial: The CB2 Cannabinoid System: A New Strategy in Neurodegenerative
      Disorder and Neuroinflammation.

PMID- 28428740
TI  - Protein Quality Control by Molecular Chaperones in Neurodegeneration.
AB  - Protein homeostasis (proteostasis) requires the timely degradation of misfolded
      proteins and their aggregates by protein quality control (PQC), of which
      molecular chaperones are an essential component. Compared with other cell types,
      PQC in neurons is particularly challenging because they have a unique cellular
      structure with long extensions. Making it worse, neurons are postmitotic, i.e.,
      cannot dilute toxic substances by division, and, thus, are highly sensitive to
      misfolded proteins, especially as they age. Failure in PQC is often associated
      with neurodegenerative diseases, such as Huntington's disease (HD), Alzheimer's
      disease (AD), Parkinson's disease (PD), and prion disease. In fact, many
      neurodegenerative diseases are considered to be protein misfolding disorders. To
      prevent the accumulation of disease-causing aggregates, neurons utilize a
      repertoire of chaperones that recognize misfolded proteins through exposed
      hydrophobic surfaces and assist their refolding. If such an effort fails,
      chaperones can facilitate the degradation of terminally misfolded proteins
      through either the ubiquitin (Ub)-proteasome system (UPS) or the autophagy
      lysosome system (hereafter autophagy). If soluble, the substrates associated with
      chaperones, such as Hsp70, are ubiquitinated by Ub ligases and degraded through
      the proteasome complex. Some misfolded proteins carrying the KFERQ motif are
      recognized by the chaperone Hsc70 and delivered to the lysosomal lumen through a
      process called, chaperone-mediated autophagy (CMA). Aggregation-prone misfolded
      proteins that remain unprocessed are directed to macroautophagy in which cargoes
      are collected by adaptors, such as p62/SQSTM-1/Sequestosome-1, and delivered to
      the autophagosome for lysosomal degradation. The aggregates that have survived
      all these refolding/degradative processes can still be directly dissolved, i.e.,
      disaggregated by chaperones. Studies have shown that molecular chaperones
      alleviate the pathogenic symptoms by neurodegeneration-causing protein
      aggregates. Chaperone-inducing drugs and anti-aggregation drugs are actively
      exploited for beneficial effects on symptoms of disease. Here, we discuss how
      chaperones protect misfolded proteins from aggregation and mediate the
      degradation of terminally misfolded proteins in collaboration with cellular
      degradative machinery. The topics also include therapeutic approaches to improve
      the expression and turnover of molecular chaperones and to develop anti
      aggregation drugs.

PMID- 28428744
TI  - Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor
      Reveals a Key Interaction Important for Channel Gating by Ivermectin.
AB  - The broad-spectrum anthelmintic drug ivermectin (IVM) activates and stabilizes an
      open-channel conformation of invertebrate chloride-selective glutamate receptors
      (GluClRs), thereby causing a continuous inflow of chloride ions and sustained
      membrane hyperpolarization. These effects suppress nervous impulses and vital
      physiological processes in parasitic nematodes. The GluClRs are pentamers.
      Homopentameric receptors assembled from the Caenorhabditis elegans (C. elegans)
      GluClalpha (GLC-1) subunit can inherently respond to IVM but not to glutamate
      (the neurotransmitter). In contrast, heteromeric GluClalpha/beta (GLC-1/GLC-2)
      assemblies respond to both ligands, independently of each other. Glutamate and
      IVM bind at the interface between adjacent subunits, far away from each other;
      glutamate in the extracellular ligand-binding domain, and IVM in the ion-channel
      pore periphery. To understand the importance of putative intersubunit contacts
      located outside the glutamate and IVM binding sites, we introduced mutations at
      intersubunit interfaces, between these two binding-site types. Then, we
      determined the effect of these mutations on the activation of the heteromeric
      mutant receptors by glutamate and IVM. Amongst these mutations, we characterized
      an alpha-subunit point mutation located close to the putative IVM-binding pocket,
      in the extracellular end of the first transmembrane helix (M1). This mutation
      (alphaF276A) moderately reduced the sensitivity of the heteromeric
      GluClalphaF276A/betaWT receptor to glutamate, and slightly decreased the receptor
      subunits' cooperativity in response to glutamate. In contrast, the alphaF276A
      mutation drastically reduced the sensitivity of the receptor to IVM and
      significantly increased the receptor subunits' cooperativity in response to IVM.
      We suggest that this mutation reduces the efficacy of channel gating, and impairs
      the integrity of the IVM-binding pocket, likely by disrupting important
      interactions between the tip of M1 and the M2-M3 loop of an adjacent subunit. We
      hypothesize that this physical contact between M1 and the M2-M3 loop tunes the
      relative orientation of the ion-channel transmembrane helices M1, M2 and M3 to
      optimize pore opening. Interestingly, pre-exposure of the GluClalphaF276A/betaWT
      mutant receptor to subthreshold IVM concentration recovered the receptor
      sensitivity to glutamate. We infer that IVM likely retained its positive
      modulation activity by constraining the transmembrane helices in a preopen
      orientation sensitive to glutamate, with no need for the aforementioned disrupted
      interactions between M1 and the M2-M3 loop.

PMID- 28428747
TI  - Editorial: Memory Processes in Medial Temporal Lobe: Experimental, Theoretical
      and Computational Approaches.

PMID- 28428745
TI  - Decreased Levels of Foldase and Chaperone Proteins Are Associated with an Early
      Onset Amyotrophic Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by a progressive upper and lower motor neuron degeneration. One of
      the peculiar clinical characteristics of ALS is the wide distribution in age of
      onset, which is probably caused by different combinations of intrinsic and
      exogenous factors. We investigated whether these modifying factors are converging
      into common pathogenic pathways leading either to an early or a late disease
      onset. This would imply the identification of phenotypic biomarkers, that can
      distinguish the two populations of ALS patients, and of relevant pathways to
      consider in a therapeutic intervention. Toward this aim a differential proteomic
      analysis was performed in peripheral blood mononuclear cells (PBMC) from a group
      of 16 ALS patients with an age of onset <=55 years and a group of 16 ALS patients
      with an age of onset >=75 years, and matched healthy controls. We identified 43
      differentially expressed proteins in the two groups of patients. Gene ontology
      analysis revealed that there was a significant enrichment in annotations
      associated with protein folding and response to stress. We next validated a
      selected number of proteins belonging to this functional group in 85 patients and
      83 age- and sex-matched healthy controls using immunoassays. The results of the
      validation study confirmed that there was a decreased level of peptidyl-prolyl
      cis-trans isomerase A (also known as cyclophilin A), heat shock protein HSP 90
      alpha, 78 kDa glucose-regulated protein (also known as BiP) and protein deglycase
      DJ-1 in PBMC of ALS patients with an early onset. Similar results were obtained
      in PBMC and spinal cord from two SOD1G93A mouse models with an early and late
      disease onset. This study suggests that a different ability to upregulate
      proteins involved in proteostasis, such as foldase and chaperone proteins, may be
      at the basis of a different susceptibility to ALS, putting forward the
      development of therapeutic approaches aiming at boosting the protein quality
      control system.

PMID- 28428746
TI  - Expression of D-Amino Acid Oxidase (DAO/DAAO) and D-Amino Acid Oxidase Activator
      (DAOA/G72) during Development and Aging in the Human Post-mortem Brain.
AB  - In the brain, D-amino acid oxidase (DAO/DAAO) mainly oxidizes D-serine, a co
      agonist of the N-methyl-D-aspartate (NMDA) receptors. Thus, DAO can regulate the
      function of NMDA receptors via D-serine breakdown. Furthermore, DAO activator
      (DAOA)/G72 has been reported as both DAOA and repressor. The co-expression of DAO
      and DAOA genes and proteins in the human brain is not yet elucidated. The aim of
      this study was to understand the regional and age span distribution of DAO and
      DAOA (mRNA and protein) in a concomitant manner. We determined DAO and DAOA mRNA
      and protein expression across six brain regions in normal human post-mortem brain
      samples (16 weeks of gestation to 91 years) using quantitative real-time reverse
      transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. We
      found higher expression of DAO mRNA in the cerebellum, whereas lower expression
      of DAO protein in the cerebellum compared to the other brain regions studied,
      which suggests post-transcriptional regulation. We detected DAOA protein but not
      DAOA mRNA in all brain regions studied, suggesting a tightly regulated
      expression. To understand this regulation at the transcriptional level, we
      analyzed DNA methylation levels at DAO and DAOA CpG sites in the cerebellum and
      frontal cortex of control human post-mortem brain obtained from Gene Expression
      Omnibus datasets. Indeed, DAO and DAOA CpG sites in the cerebellum were
      significantly more methylated than those in the frontal cortex. While
      investigating lifespan effects, we found that DAO mRNA levels were positively
      correlated with age <2 years in the cerebellum and amygdala. We also detected a
      significant positive correlation (controlled for age) between DAO and DAOA
      protein in all of the brain regions studied except for the frontal cortex. In
      summary, DAO and DAOA expression in the human brain are both age and brain region
      dependent.

PMID- 28428748
TI  - Resting-State Neuroimaging and Neuropsychological Findings in Opioid Use Disorder
      during Abstinence: A Review.
AB  - Dependence to opiates, including illicit heroin and prescription pain killers,
      and treatment of the opioid use disorder (OUD) have been longstanding problems
      over the world. Despite intense efforts to scientific investigation and public
      health care, treatment outcomes have not significantly improved for the past 50
      years. One reason behind the continuing use of heroin worldwide despite such
      efforts is its highly addictive nature. Brain imaging studies over the past two
      decades have made significant contribution to the understanding of the addictive
      properties as to be due in part to biological processes, specifically those in
      the brain structure and function. Moreover, traditional clinical neuropsychology
      studies also contribute to the account in part for the treatment-refractory
      nature of the drug abuse. However, there is a gap between those studies, and the
      rates of relapse are still high. Thus, a multidisciplinary approach is needed to
      understand the fundamental neural mechanism of OUD. How does the brain of an OUD
      patient functionally and cognitively differ from others? This brief review is to
      compare and contrast the current literature on non-invasive resting state
      neuroimaging and clinical neuropsychological studies with the focus on the
      abstinence stage in OUD. The results show as follow: Brain connectivity strength
      in the reward system, dysregulation of circuits associated with emotion and
      stress, enhanced beta and alpha power activity, and high impulsivity are induced
      by OUD.Some recovery signs in cognition are demonstrated in OUD subjects after
      prolonged abstinence, but not in the subjects undergoing methadone
      treatment.Normalization in the composition of brain oscillations especially in
      the temporal region is induced and restored by methadone treatment in roughly 6
      months in mean duration for OUDs having a mean opioid-use history of 10 years. We
      hope that the review provides valuable implications for clinical research and
      practice and paves a new insight into the future path to the identification of
      potential biomarkers and clinical outcome predictors in OUD in the domains of
      brain regions, functions, and behaviors.

PMID- 28428749
TI  - Deep Brain Stimulation Improves the Symptoms and Sensory Signs of Persistent
      Central Neuropathic Pain from Spinal Cord Injury: A Case Report.
AB  - Central neuropathic pain (CNP) is a significant problem after spinal cord injury
      (SCI). Pharmacological and non-pharmacological approaches may reduce the
      severity, but relief is rarely substantial. While deep brain stimulation (DBS)
      has been used to treat various chronic pain types, the technique has rarely been
      used to attenuate CNP after SCI. Here we present the case of a 54-year-old female
      with incomplete paraplegia who had severe CNP in the lower limbs and buttock
      areas since her injury 30 years prior. She was treated with bilateral DBS of the
      midbrain periaqueductal gray (PAG). The effects of this stimulation on CNP
      characteristics, severity and pain-related sensory function were evaluated using
      the International SCI Pain Basic Data Set (ISCIPBDS), Neuropathic Pain Symptom
      Inventory (NPSI), Multidimensional Pain Inventory and Quantitative Sensory
      Testing before and periodically after initiation of DBS. After starting DBS
      treatment, weekly CNP severity ratings rapidly decreased from severe to minimal,
      paralleled by a substantial reduction in size of the painful area, reduced pain
      impact and reversal of pain-related neurological abnormalities, i.e., dynamic
      mechanical and cold allodynia. She discontinued pain medication on study week 24.
      The improvement has been consistent. The present study expands on previous
      findings by providing in-depth assessments of symptoms and signs associated with
      CNP. The results of this study suggest that activation of endogenous pain
      inhibitory systems linked to the PAG can eliminate CNP in some people with SCI.
      More research is needed to better-select appropriate candidates for this type of
      therapy. We discuss the implications of these findings for understanding the
      brainstem's control of chronic pain and for future progress in using analgesic
      DBS in the central gray.

PMID- 28428750
TI  - Applying an Archetype-Based Approach to Electroencephalography/Event-Related
      Potential Experiments in the EEGBase Resource.
AB  - PURPOSE: The purpose of this study is to investigate the feasibility of applying
      openEHR (an archetype-based approach for electronic health records
      representation) to modeling data stored in EEGBase, a portal for experimental
      electroencephalography/event-related potential (EEG/ERP) data management. The
      study evaluates re-usage of existing openEHR archetypes and proposes a set of new
      archetypes together with the openEHR templates covering the domain. The main
      goals of the study are to (i) link existing EEGBase data/metadata and openEHR
      archetype structures and (ii) propose a new openEHR archetype set describing the
      EEG/ERP domain since this set of archetypes currently does not exist in public
      repositories. METHODS: The main methodology is based on the determination of the
      concepts obtained from EEGBase experimental data and metadata that are
      expressible structurally by the openEHR reference model and semantically by
      openEHR archetypes. In addition, templates as the third openEHR resource allow us
      to define constraints over archetypes. Clinical Knowledge Manager (CKM), a public
      openEHR archetype repository, was searched for the archetypes matching the
      determined concepts. According to the search results, the archetypes already
      existing in CKM were applied and the archetypes not existing in the CKM were
      newly developed. openEHR archetypes support linkage to external terminologies. To
      increase semantic interoperability of the new archetypes, binding with the
      existing odML electrophysiological terminology was assured. Further, to increase
      structural interoperability, also other current solutions besides EEGBase were
      considered during the development phase. Finally, a set of templates using the
      selected archetypes was created to meet EEGBase requirements. RESULTS: A set of
      eleven archetypes that encompassed the domain of experimental EEG/ERP
      measurements were identified. Of these, six were reused without changes, one was
      extended, and four were newly created. All archetypes were arranged in the
      templates reflecting the EEGBase metadata structure. A mechanism of odML
      terminology referencing was proposed to assure semantic interoperability of the
      archetypes. The openEHR approach was found to be useful not only for clinical
      purposes but also for experimental data modeling.

PMID- 28428751
TI  - Identification of NF-kappaB as Determinant of Posttraumatic Stress Disorder and
      Its Inhibition by the Chinese Herbal Remedy Free and Easy Wanderer.
AB  - Posttraumatic stress disorder (PTSD) is a mental disorder developing after
      exposure to traumatic events. Although psychotherapy reveals some therapeutic
      effectiveness, clinically sustainable cure is still uncertain. Some Chinese
      herbal formulae are reported to work well clinically against mental diseases in
      Asian countries, but the safety and their mode of action are still unclear. In
      this study, we investigated the mechanisms of Chinese remedy free and easy
      wanderer (FAEW) on PTSD. We used a reverse pharmacology approach combining
      clinical data to search for mechanisms of PTSD with subsequent in vitro
      verification and bioinformatics techniques as follows: (1) by analyzing
      microarray-based transcriptome-wide mRNA expression profiling of PTSD patients;
      (2) by investigating the effect of FAEW and the antidepressant control drug
      fluoxetine on the transcription factor NF-kappaB using reporter cell assays and
      western blotting; (3) by performing molecular docking and literature data mining
      based on phytochemical constituents of FAEW. The results suggest an involvement
      of inflammatory processes mediated through NF-kappaB in the progression of PTSD.
      FAEW was non-cytotoxic in vitro and inhibited NF-kappaB activity and p65 protein
      expression. FAEW's anti-inflammatory compounds, i.e., paeoniflorin,
      isoliquiritin, isoliquiritin apioside and ononin were evaluated for binding to
      IkappaK and p65-RelA in a molecular docking approach. Paeoniflorin, albiflorin,
      baicalin, isoliquiritin and liquiritin have been reported to relieve depression
      in vivo or in clinical trials, which might be the active ingredients for FAEW
      against PTSD.

PMID- 28428752
TI  - Desensitizing Mitochondrial Permeability Transition by ERK-Cyclophilin D Axis
      Contributes to the Neuroprotective Effect of Gallic Acid against Cerebral
      Ischemia/Reperfusion Injury.
AB  - Ischemic stroke is a devastating disease with complex pathophysiology. Much
      evidence confirms that opening of the mitochondrial permeability transition pore
      (MPTP) is related with mitochondrial dysfunction to apoptosis in ischemic stroke,
      thus elucidating its signaling mechanism and screening novel MPTP inhibitor is
      therefore of paramount importance. Our earlier studies identified that gallic
      acid (GA), a naturally occurring plant phenol, endows with effect on inhibition
      of mitochondrial dysfunction, which has significant neuroprotective effect in
      cerebral ischemia/reperfusion injury. However, its molecular mechanisms
      regulating mitochondrial dysfunction remain elusive. Here, we uncover a role of
      GA in protecting mitochondria via MPTP inhibition. In addition to inhibit CypD
      binding to adenine nucleotide translocator, GA potentiates extracellular signal
      regulated kinases (ERK) phosphorylation, leading to a decrease in cyclophilin D
      (CypD) expression, resulting in a desensitization to induction of MPTP, thus
      inhibiting caspase activation and ultimately giving rise to cellular survival.
      Our study firstly identifies ERK-CypD axis is one of the cornerstones of the cell
      death pathways following ischemic stroke, and confirms GA is a novel inhibitor of
      MPTP, which inhibits apoptosis depending on regulating the ERK-CypD axis.

PMID- 28428753
TI  - A Clinical Perspective of Anti-Fibrotic Therapies for Cardiovascular Disease.
AB  - Cardiac fibrosis are central to various cardiovascular diseases. Research on the
      mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in
      recent years. However, while many anti-fibrotic treatments have been studied in
      animal models and seem promising, translation of experimental findings into human
      patients has been rather limited. Thus, several potential new treatments which
      have shown to reduce cardiac fibrosis in animal models have either not been
      tested in humans or proved to be disappointing in clinical trials. A majority of
      clinical studies are of small size or have not been maintained for long enough
      periods. In addition, although some conventional therapies, such as renin
      angiotensin-aldosterone system (RAAS) inhibitors, have been shown to reduce
      cardiac fibrosis in humans, cardiac fibrosis persists in patients with heart
      failure even when treated with these conventional therapies, indicating a need to
      develop novel and effective anti-fibrotic therapies in cardiovascular disease. In
      this review article, we summarize anti-fibrotic therapies for cardiovascular
      disease in humans, discuss the limitations of currently used therapies, along
      with possible reasons for the failure of so many anti-fibrotic drugs at the
      clinical level. We will then explore the future directions of anti-fibrotic
      therapies on cardiovascular disease, and this will include emerging anti
      fibrotics that show promise, such as relaxin. A better understanding of the
      differences between animal models and human pathology, and improved insight into
      carefully designed trials on appropriate end-points and appropriate dosing need
      to be considered to identify more effective anti-fibrotics for treating
      cardiovascular fibrosis in human patients.

PMID- 28428754
TI  - Pu-erh Tea Water Extract Mediates Cell Cycle Arrest and Apoptosis in MDA-MB-231
      Human Breast Cancer Cells.
AB  - Pu-erh tea is believed to have health benefits, the growth inhibition activity of
      Pu-erh tea on breast cancer cell has not been investigated. In this study, we
      examined the activity of Pu-erh tea water extract on apoptosis and cell cycle
      arrest in the human breast adenocarcinoma cell line MDA-MB-231 and clarified its
      underlying mechanism of action. We found that Pu-erh tea extract inhibited cell
      proliferation and induced apoptosis in a dose-dependent manner. We also found
      that Pu-erh tea extract inhibited tumor cell growth within 24 h via accumulation
      of cells in S phase. Further experiments showed that at 24 h, Pu-erh tea extract
      up-regulated the expressions of P-p53 (Ser15), p21 and P-JNK and down-regulated
      the expressions of PCNA, CyclinD1 and CyclinE at the protein level in MDA-MB-231
      cells. In particular, the JNK-specific inhibitor SP600125 restored the induction
      of P-JNK, P-p53 (Ser15), p21, CyclinD1 and CyclinE by Pu-erh tea extract. Our
      results indicate that Pu-erh tea water extract inhibits cell proliferation of MDA
      MB-231 cells through the induction of apoptosis and the stimulation of cell cycle
      arrest, which is mediated via activation of the JNK-related pathway.

PMID- 28428755
TI  - Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in
      scn1a Mutant Zebrafish.
AB  - Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe
      seizures and prominent co-morbidities (e.g., physical, intellectual
      disabilities). More than 85% of the DS patients carry an SCN1A mutation (sodium
      channel, voltage gated, type I alpha subunit). Although numerous anti-epileptic
      drugs have entered the market since 1990, these drugs often fail to adequately
      control seizures in DS patients. Nonetheless, current clinical data shows
      significant seizure reduction in DS patients treated with the serotonergic (5
      hydroxytryptamine, 5-HT) drug fenfluramine (FA). Recent preclinical research
      confirmed the anti-epileptiform activity of FA in homozygous scn1a mutant
      zebrafish larvae that mimic DS well. Here we explored the anti-epileptiform
      mechanisms of FA by investigating whether selective agonists/antagonists of
      specific receptor subtypes were able to counteract the FA-induced inhibition of
      seizures and abnormal brain discharges observed in the scn1a mutants. We show
      that antagonists of 5-HT1D and 5-HT2C receptor subtypes were able to do so (LY
      310762 and SB 242084, respectively), but notably, a 5-HT2A-antagonist
      (ketanserin) was not. In addition, exploring further the mechanism of action of
      FA beyond its serotonergic profile, we found that the anti-epileptiform brain
      activity of FA was significantly abolished when it was administered in
      combination with a sigma1-agonist (PRE 084). Our study therefore provides the
      first evidence of an involvement of the sigma1 receptor in the mechanism of FA.
      We further show that the level of some neurotransmitters [i.e., dopamine and
      noradrenaline (NAD)] in head homogenates was altered after FA treatment, whereas
      gamma-aminobutyric acid (GABA) and glutamate levels were not. Of interest, NAD
      decreasing drugs have been employed successfully in the treatment of neurological
      diseases; including epilepsy and this effect could contribute to the therapeutic
      effect of the compound. In summary, we hypothesize that the anti-epileptiform
      activity of FA not only originates from its 5-HT1D- and 5-HT2C-agonism, but
      likely also from its ability to block sigma1 receptors. These findings will help
      in better understanding the pharmacological profile of compounds that is critical
      for their applicability in the treatment of DS and possibly also other drug
      resistant epilepsies.

PMID- 28428757
TI  - Circadian Rhythm in Kidney Tissue Oxygenation in the Rat.
AB  - Blood pressure, renal hemodynamics, electrolyte, and water excretion all display
      diurnal oscillation. Disturbance of these patterns is associated with
      hypertension and chronic kidney disease. Kidney oxygenation is dependent on
      oxygen delivery and consumption that in turn are determined by renal hemodynamics
      and metabolism. We hypothesized that kidney oxygenation also demonstrates 24-h
      periodicity. Telemetric oxygen-sensitive carbon paste electrodes were implanted
      in Sprague-Dawley rats (250-300 g), either in renal medulla (n = 9) or cortex (n
      = 7). Arterial pressure (MAP) and heart rate (HR) were monitored by telemetry in
      a separate group (n = 8). Data from 5 consecutive days were analyzed for
      rhythmicity by cosinor analysis. Diurnal electrolyte excretion was assessed by
      metabolic cages. During lights-off, oxygen levels increased to 105.3 +/- 2.1% in
      cortex and 105.2 +/- 3.8% in medulla. MAP was 97.3 +/- 1.5 mmHg and HR was 394.0
      +/- 7.9 bpm during lights-off phase and 93.5 +/- 1.3 mmHg and 327.8 +/- 8.9 bpm
      during lights-on. During lights-on, oxygen levels decreased to 94.6 +/- 1.4% in
      cortex and 94.2 +/- 8.5% in medulla. There was significant 24-h periodicity in
      cortex and medulla oxygenation. Potassium excretion (1,737 +/- 779 vs. 895 +/-
      132 MUmol/12 h, P = 0.005) and the distal Na+/K+ exchange (0.72 +/- 0.02 vs. 0.59
      +/- 0.02 P < 0.001) were highest in the lights-off phase, this phase difference
      was not found for sodium excretion (P = 0.4). It seems that oxygen levels in the
      kidneys follow the pattern of oxygen delivery, which is known to be determined by
      renal blood flow and peaks in the active phase (lights-off).

PMID- 28428756
TI  - Neck Circumference Is Associated with Muscle Sympathetic Nerve Activity in
      Overweight and Obese Men but Not Women.
AB  - Background: Neck circumference (NC) is a predictor of cardiometabolic risk. The
      objective of this study was to explore the relationship of NC to muscle
      sympathetic nerve activity (MSNA) within an overweight and obese population.
      Methods: The study design was a retrospective cross-sectional analysis. Un
      medicated persons (72 men, 53 postmenopausal women) aged 56 +/- 1 years (mean +/-
      SEM) with body mass index (BMI) 32.8 +/- 0.4 kg/m2, were studied. NC was measured
      together with traditional anthropometric measures, supine blood pressure, fasting
      blood lipids, insulin, and glucose. Insulin sensitivity was assessed by
      homeostasis model (HOMA-IR) and Matsuda Insulin Sensitivity Index (ISI) derived
      from 75-g oral glucose tolerance test. Resting multiunit MSNA was recorded by
      microneurography in the peroneal nerve and expressed as burst frequency and burst
      incidence. Results: Men within the highest tertile of NC had significantly higher
      fasting and post-glucose plasma insulin levels (insulin AUC0-120), HOMA-IR, non
      esterified fatty acids, MSNA (45 +/- 2 vs. 36 +/- 2 bursts per min; 69 +/- 3 vs.
      58 +/- 3 bursts per 100 hb) and heart rate, and lower Matsuda ISI compared to men
      in the lowest tertile (P all <0.05). In stepwise regression analyses, NC alone
      explained 12%, and together with insulin AUC0-120 it accounted for 22%, of the
      variance in MSNA in men. In women, NC was associated with anthropometric measures
      but not with MSNA or metabolic indices. Conclusions: Among overweight and obese
      men, NC was independently associated with elevated MSNA and hyperinsulinemia, and
      thus may be relevant to cardiometabolic risk prediction. The biological basis of
      gender differences merits further elucidation.

PMID- 28428758
TI  - Modulation of Asymmetric Flux in Heterotypic Gap Junctions by Pore Shape,
      Particle Size and Charge.
AB  - Gap junction channels play a vital role in intercellular communication by
      connecting cytoplasm of adjoined cells through arrays of channel-pores formed at
      the common membrane junction. Their structure and properties vary depending on
      the connexin isoform(s) involved in forming the full gap junction channel. Lack
      of information on the molecular structure of gap junction channels has limited
      the development of computational tools for single channel studies. Currently, we
      rely on cumbersome experimental techniques that have limited capabilities. We
      have earlier reported a simplified Brownian dynamics gap junction pore model and
      demonstrated that variations in pore shape at the single channel level can
      explain some of the differences in permeability of heterotypic channels observed
      in in vitro experiments. Based on this computational model, we designed
      simulations to study the influence of pore shape, particle size and charge in
      homotypic and heterotypic pores. We simulated dye diffusion under whole cell
      voltage clamping. Our simulation studies with pore shape variations revealed a
      pore shape with maximal flux asymmetry in a heterotypic pore. We identified pore
      shape profiles that match the in silico flux asymmetry results to the in vitro
      results of homotypic and heterotypic gap junction formed out of Cx43 and Cx45.
      Our simulation results indicate that the channel's pore-shape established flux
      asymmetry and that flux asymmetry is primarily regulated by the sizes of the
      conical and/or cylindrical mouths at each end of the pore. Within the set range
      of particle size and charge, flux asymmetry was found to be independent of
      particle size and directly proportional to charge magnitude. While particle
      charge was vital to creating flux asymmetry, charge magnitude only scaled the
      observed flux asymmetry. Our studies identified the key factors that help predict
      asymmetry. Finally, we suggest the role of such flux asymmetry in creating
      concentration imbalances of messenger molecules in cardiomyocytes. We also assess
      the potency of fibroblasts in aggravating such imbalances through Cx43-Cx45
      heterotypic channels in fibrotic heart tissue.

PMID- 28428759
TI  - Morphological Regeneration and Functional Recovery of Neuromuscular Junctions
      after Tourniquet-Induced Injuries in Mouse Hindlimb.
AB  - Tourniquet application and its subsequent release cause serious injuries to the
      skeletal muscle, nerve, and neuromuscular junction (NMJ) due to mechanical
      compression and ischemia-reperfusion (IR). Monitoring structural and functional
      repair of the NMJ, nerve, and skeletal muscle after tourniquet-induced injuries
      is beneficial in exploring potential cellular and molecular mechanisms
      responsible for tourniquet-induced injuries, and for establishing effective
      therapeutic interventions. Here, we observed long-term morphological and
      functional changes of the NMJ in a murine model of tourniquet-induced hindlimb
      injuries. Unilateral hindlimbs of C57/BL6 mice were subjected to 3 h of
      tourniquet by placing an orthodontic rubber band, followed by varied periods of
      tourniquet release (1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks). NMJ
      morphology in the gastrocnemius muscle was imaged, and the endplate potential
      (EPP) was recorded to evaluate NMJ function. In NMJs, nicotinic acetylcholine
      receptor (nAChR) clusters normally displayed an intact, pretzel-like shape, and
      all nAChR clusters were innervated (100%) by motor nerve terminals. During 3 h of
      tourniquet application and varied periods of tourniquet release, NMJs in the
      gastrocnemius muscle were characterized by morphological and functional changes.
      At 1 day and 3 days of tourniquet release, nAChR clusters retained normal,
      pretzel-like shapes, whereas motor nerve terminals were completely destroyed and
      no EPPs recorded. From 1 to 6 weeks of tourniquet release, motor nerve terminals
      gradually regenerated, even reaching that seen in sham mice, whereas nAChR
      clusters were gradually fragmented with prolongation of tourniquet release.
      Additionally, the amplitude of EPPs gradually increased with prolongation of
      tourniquet release. However, even at 6 weeks after tourniquet release, the
      amplitude of EPPs did not restore to the level seen in sham mice (13.9 +/- 1.1
      mV, p < 0.05 vs. sham mice, 29.8 +/- 1.0 mV). The data suggest that tourniquet
      application and subsequent release impair the structure and function of NMJs.
      Morphological change in motor nerve terminals is faster than in nAChR clusters in
      NMJs. Slow restoration of fragmented nAChR clusters possibly dampens
      neuromuscular transmission during the long phase following tourniquet release.

PMID- 28428760
TI  - The Variation Tendency of Polyamines Forms and Components of Polyamine Metabolism
      in Zoysiagrass (Zoysia japonica Steud.) to Salt Stress with Exogenous Spermidine
      Application.
AB  - To understand dynamic changes in polyamines (PAs) forms and components of
      polyamine metabolism in zoysiagrass (Zoysia japonica Steud.) response to salt
      stress with exogenous spermidine (Spd) application, two Chinese zoysia cultivars,
      z081 and z057, were exposed to sodium chloride stress for 2, 4, 6, and 8 days.
      The z057 cultivar possesses higher salinity tolerance than the z081 cultivar.
      Salt stress decreased the zoysiagrass fresh weight (FW) and increased free Spd
      and spermine (Spm) levels and soluble and insoluble putrescine (Put), Spd and Spm
      levels in both cultivars. Moreover, salt stress enhanced the activities of
      arginine decarboxylase (ADC), ornithine decarboxylase (ODC), S-adenosylmethionine
      decarboxylase (SAMDC), and diamine oxidase (DAO). Exogenous Spd increased PA
      metabolism and ADC, SAMDC, and DAO activities and decreased free Put levels under
      salt stress conditions in both cultivars. In addition, structural equation
      modeling (SEM) showed that ODC, SAMDC, and DAO contributed to PA metabolism, and
      endogenous Spd levels also contributed to endogenous Spm levels. Free PAs may be
      the primary factor influencing the variation of other PA forms. SEM also
      indicated that ADC and polyamine oxidase (PAO) play a limited role in enhancing
      zoysia salt tolerance via PA metabolism under salt stress.

PMID- 28428761
TI  - Effect of Case Management Interventions for Patients with Substance Use
      Disorders: A Systematic Review.
AB  - BACKGROUND: Substance use disorder (SUD) is an important health problem that
      requires a complex range of care because of the chronic nature of the disorder
      and the multiple psychosocial problems involved. Current outpatient programs
      often have difficulties in delivering and coordinating ongoing care and access to
      different health-care providers. Various case management (CM) models have been
      developed, first for patients in other psychiatric domains and then for patients
      with SUD, in order to improve treatment outcomes. AIM: This paper aims to assess
      the effectiveness of CM for patients with SUD. METHODS: We performed a systematic
      review of CM interventions for patients with SUD by analyzing randomized
      controlled studies published on the subject between 1996 and 2016 found on the
      electronic database PubMed. RESULTS AND CONCLUSION: Fourteen studies were
      included in the analysis. Differences between studies in outcome measures,
      populations included, and intervention characteristics made it difficult to
      compare results. Most of these studies reported improvement in some of the chosen
      outcomes. Treatment adherence mostly improved, but substance use was reported to
      decrease in only a third of the studies. Overall functioning improved in about
      half of the studies. The heterogeneity of the results might be linked to these
      differences between studies. Further research is needed in the field.

PMID- 28428762
TI  - Gendered Pathways: How Mathematics Ability Beliefs Shape Secondary and
      Postsecondary Course and Degree Field Choices.
AB  - Do mathematics ability beliefs explain gender gaps in the physical science,
      engineering, mathematics, and computer science fields (PEMC) and other science
      fields? We leverage U.S. nationally representative longitudinal data to estimate
      gendered differences in girls' and boys' perceptions of mathematics ability with
      the most difficult or challenging material. Our analyses examine the potentially
      interacting effects of gender and these ability beliefs on students' pathways to
      scientific careers. Specifically, we study how beliefs about ability with
      challenging mathematics influence girls' and boys' choices to pursue PEMC
      degrees, evaluating educational milestones over a 6-year period: advanced science
      course completion in secondary school and postsecondary major retention and
      selection. Our findings indicate even at the same levels of observed ability,
      girls' mathematics ability beliefs under challenge are markedly lower than those
      of boys. These beliefs matter over time, potentially tripling girls' chances of
      majoring in PEMC sciences, over and above biological science fields, all else
      being equal. Implications and potential interventions are discussed.

PMID- 28428764
TI  - Employee Age Alters the Effects of Justice on Emotional Exhaustion and
      Organizational Deviance.
AB  - Fairness in the workplace attenuates a host of negative individual and
      organizational outcomes. However, research on the psychology of aging challenges
      the assumption that fairness operates similarly across different age groups. The
      current research explored how older workers, vis-a-vis younger workers, react to
      perceptions of fairness. Integrating socioemotional selectivity theory and the
      multiple needs theory of organizational justice, we generated novel predictions
      regarding the relations between perceptions of workplace justice, emotional
      exhaustion, and employee deviance. Specifically, we hypothesized and found that
      employee age moderates the negative relation between justice facets and deviance
      (Study 1) and emotional exhaustion (Study 2). We also found that emotional
      exhaustion mediates the differential effects of justice on deviance, and that
      this relation depends on employee age (Study 2). Relative to younger workers,
      older workers are more sensitive to informational and interpersonal justice; in
      contrast, relative to older workers, younger workers are more sensitive to
      distributive and procedural justice. The research supports and extends existing
      theory on organizational justice and on the psychology of aging. Moreover, it
      highlights the importance of considering employee age as a focal variable of
      interest in the study of justice processes, and in organizational research more
      generally.

PMID- 28428763
TI  - ADHD, Lifestyles and Comorbidities: A Call for an Holistic Perspective - from
      Medical to Societal Intervening Factors.
AB  - The review examines Attention Deficit Hyperactivity Disorder (ADHD in its Child
      and Adult form) and its various presentations (Hyperactive Impulsive,
      Inattentive, and Combined) with a particular focus on environmental (incl. social
      factors), lifestyles and comorbidities. It is argued that ADHD is best understood
      in a holistic and interactive context and a vast empirical literature is
      presented to illustrate the point: Environmental factors include stress in
      general as well as exposure to toxins (phthalates, bisphenol A). Social factors
      are illustrated by effects of social deprivation and seduction to unhealthy
      lifestyles. Maternal lifestyle during pregnancy is pointed out (particularly her
      exposure to nicotine, alcohol, caffeine, and drugs, even seemingly benign
      medications like acetaminophen), which all tend to be related to ADHD. Family
      environment is discussed with respect to protective effect of (mainly
      authoritative and autocratic) parenting styles. Societal factors include mainly
      economic and political issues: income inequality and poverty (low SES is an ADHD
      risk factor) and a growing moral dilemma between a humanistic effort to globally
      spread the knowledge of ADHD and the medicalization and commercialization of the
      disorder. The second part of the review is devoted to ADHD related lifestyles and
      resulting comorbidities (e.g., food addiction and obesity, substance abuse,
      electronic media dependencies and conduct and personality disorders). Although
      ADHD is a neurodevelopmental disorder, its assessment and treatment are also
      linked to environmental, behavioral and social factors and their interactions.

PMID- 28428765
TI  - Content Analysis of the Construction of Self and Others in Women with Bulimia
      Nervosa.
AB  - The purpose of this study was to explore the content of personal constructs in
      people diagnosed with bulimia nervosa (BN). We expected to find differences in
      the predominant content of the construct systems between women with and without
      BN. We analyzed the constructs elicited using the repertory grid technique from
      120 women aged between 18 to 45 years, divided into two groups: a clinical group
      of women diagnosed with bulimia (n = 62) and a control group of university
      students (n = 58). The constructs were categorized using the Classification
      System for Personal Constructs (CSPC), composed of six themes which are broken
      down into 45 categories. For this study, a new area called "Physical" was
      included, and it consists of three categories. The results indicated that women
      diagnosed with bulimia used significantly more constructs related to the body,
      while the control group used more constructs from the personal area. In addition,
      the congruent constructs from the clinical sample were predominantly moral, or
      related to values and interests, while discrepant constructs were personal and
      physical. The findings provide evidence for the clinical use of the CSPC as an
      instrument for exploring the content of personal meaning systems. Understanding
      the patient's personal constructions about herself and others is useful for
      treatment. Moreover, it is important for clinicians to explore the content of
      constructs related to symptomatic areas, which could be hindering change, and
      focus on them to facilitate improvement.

PMID- 28428766
TI  - Episodic Specificity in Acquiring Thematic Knowledge of Novel Words from
      Descriptive Episodes.
AB  - The current study examined whether thematic relations of the novel words could be
      acquired via descriptive episodes, and if yes, whether it could be generalized to
      thematically related words in a different scenario. In Experiment 1, a lexical
      decision task was used where the novel words served as primes for target words in
      four conditions: (1) corresponding concepts of the novel words, (2) thematically
      related words in the same episodes as that in learning condition, (3)
      thematically related words in different episodes, or (4) unrelated words served
      as targets. Event related potentials elicited by the targets revealed that
      compared to the unrelated words, the corresponding concepts and thematically
      related words in the same episodes elicited smaller N400s with a frontal-central
      distribution, whereas the thematically related words in different episodes
      elicited an enhanced late positive component. Experiment 2 further showed a
      priming effect of the corresponding concepts on the thematically related words in
      the same episodes as well as in a different episode, indicating that the absence
      of a priming effect of the learned novel words on the thematically related words
      in different episode could not be attributed to inappropriate selection of
      thematically related words in the two conditions. These results indicate that
      only the corresponding concepts and the thematically related words in the
      learning episodes were successfully primed, whereas the thematic association
      between the novel words and the thematically related words in different scenarios
      could only be recognized in a late processing stage. Our findings suggest that
      thematic knowledge of novel words is organized via separate scenarios, which are
      represented in a clustered manner in the semantic network.

PMID- 28428767
TI  - Social Cognitive Training Improves Emotional Processing and Reduces Aggressive
      Attitudes in Ex-combatants.
AB  - Emotional processing (EP) is a complex cognitive function necessary to
      successfully adjust to social environments where we need to interpret and respond
      to cues that convey threat or reward signals. Ex-combatants have consistently
      shown atypical EP as well as poor social interactions. Available reintegration
      programs aim to facilitate the re-adaptation of ex-combatants to their
      communities. However, they do not incorporate actions to improve EP and to
      enhance cognitive-emotional regulation. The present study was aimed at evaluating
      the usefulness of an intervention focused on Social Cognitive Training (SCT),
      which was designed to equip ex-combatants enrolled in the Social Reintegration
      Route with EP and social cognition skills. A group of 31 ex-combatants (mean age
      of 37.2, 29 men) from Colombian illegal armed groups were recruited into this
      study. Of these, 16 were invited to take part in a SCT and the other continued
      with the conventional reintegration intervention. Both groups underwent 12
      training sessions in a period 12-14 weeks. They were assessed with a
      comprehensive protocol which included Psychosocial, Behavioral, and Emotion
      Processing instruments. The scores on these instruments prior to and after the
      intervention were compared within and between groups. Both groups were matched at
      baseline. Ex-combatants receiving the SCT experienced significant improvements in
      EP and a reduction in aggressive attitudes, effects not observed in those
      continuing the conventional reintegration intervention. This is the first study
      that achieves such outcomes in such a population using SCT intervention. We
      discuss the implications of such results toward better social reintegration
      strategies.

PMID- 28428768
TI  - The BEST Dataset of Language Proficiency.

PMID- 28428769
TI  - Individualized Repetitive Transcranial Magnetic Stimulation Treatment in Chronic
      Tinnitus?
AB  - BACKGROUND: Prefrontal and temporo-parietal repetitive transcranial magnetic
      stimulation (rTMS) in patients suffering from chronic tinnitus have shown
      significant but only moderate effectiveness with high interindividual variability
      in treatment response. This open-label pilot study was designed to examine the
      general feasibility of an individualized fronto-temporal rTMS protocol and to
      explore what criteria are needed for a more detailed evaluation in randomized
      clinical studies. METHODS: During the first session of a 2-week rTMS protocol, we
      applied different rTMS protocols to the left and right temporo-parietal and
      dorsolateral prefrontal cortex (DLPFC) in 25 tinnitus patients. Short trains of
      1, 5, 10, and 20 Hz and continuous theta burst stimulation were applied, and
      patients were asked for immediate tinnitus reductions after each train. If a
      patient reported such improvements, rTMS treatment was applied over nine sessions
      with a combined protocol consisting of the most effective frontal and the most
      effective temporo-parietal stimulation protocol. Those patients who did not
      improve after the test session were treated with a standard prefrontal plus
      temporo-parietal protocol (20 Hz over left DLPFC + 1 Hz over temporo-parietal
      cortex). RESULTS: Almost half of the patients (12 of 25) reported immediate
      tinnitus reductions during the test session. In this group, the mean pre- to post
      treatment amelioration in the tinnitus questionnaire was higher (medium to high
      effect sizes) in contrast to the patients who did not respond to the test
      session. Treatment outcome remained stable over a follow-up period of 10 weeks.
      DISCUSSION: Individualized rTMS was shown to be feasible and effective in chronic
      tinnitus. The results obtained from this study provide tentative evidence in
      support of an individualized rTMS treatment approach and might provide a basis
      for a "tailored" application of rTMS in tinnitus and other neuropsychiatric
      disorders.

PMID- 28428770
TI  - Prolonged Walking with a Wearable System Providing Intelligent Auditory Input in
      People with Parkinson's Disease.
AB  - Rhythmic auditory cueing is a well-accepted tool for gait rehabilitation in
      Parkinson's disease (PD), which can now be applied in a performance-adapted
      fashion due to technological advance. This study investigated the immediate
      differences on gait during a prolonged, 30 min, walk with performance-adapted
      (intelligent) auditory cueing and verbal feedback provided by a wearable sensor
      based system as alternatives for traditional cueing. Additionally, potential
      effects on self-perceived fatigue were assessed. Twenty-eight people with PD and
      13 age-matched healthy elderly (HE) performed four 30 min walks with a wearable
      cue and feedback system. In randomized order, participants received: (1)
      continuous auditory cueing; (2) intelligent cueing (10 metronome beats triggered
      by a deviating walking rhythm); (3) intelligent feedback (verbal instructions
      triggered by a deviating walking rhythm); and (4) no external input. Fatigue was
      self-scored at rest and after walking during each session. The results showed
      that while HE were able to maintain cadence for 30 min during all conditions,
      cadence in PD significantly declined without input. With continuous cueing and
      intelligent feedback people with PD were able to maintain cadence (p = 0.04),
      although they were more physically fatigued than HE. Furthermore, cadence
      deviated significantly more in people with PD than in HE without input and
      particularly with intelligent feedback (both: p = 0.04). In PD, continuous and
      intelligent cueing induced significantly less deviations of cadence (p = 0.006).
      Altogether, this suggests that intelligent cueing is a suitable alternative for
      the continuous mode during prolonged walking in PD, as it induced similar effects
      on gait without generating levels of fatigue beyond that of HE.

PMID- 28428771
TI  - Corrigendum: Twenty-Year Clinical Progression of Dysferlinopathy in Patients from
      Dagestan.
AB  - [This corrects the article on p. 77 in vol. 8, PMID: 28337173.].

PMID- 28428772
TI  - Molecular Characterization of Staphylococcus aureus Isolated from Bovine Mastitis
      and Close Human Contacts in South African Dairy Herds: Genetic Diversity and
      Inter-Species Host Transmission.
AB  - Staphylococcus aureus is one of the most common etiological agents of contagious
      bovine mastitis worldwide. The purpose of this study was to genetically
      characterize a collection of S. aureus isolates (bovine = 146, human = 12)
      recovered from cases of bovine mastitis and nasal swabs of close human contacts
      in the dairy environment. Isolates were screened for a combination of clinically
      significant antimicrobial and virulence gene markers whilst the molecular
      epidemiology of these isolates and possible inter-species host transmission was
      investigated using a combination of genotyping techniques. None of the isolates
      under evaluation tested positive for methicillin or vancomycin resistance
      encoding genes. Twenty seven percent of the bovine S. aureus isolates tested
      positive for one or more of the pyrogenic toxin superantigen (PTSAg) genes with
      the sec and sell genes predominating. Comparatively, 83% of the human S. aureus
      isolates tested positive for one or more PTSAg genes with a greater variety of
      genes being detected. Genomic DNA macrorestriction followed by pulsed-field gel
      electrophoresis (PFGE) of the bovine isolates generated 58 electrophoretic
      patterns which grouped into 10 pulsotypes at an 80% similarity level. The
      majority of the bovine isolates, 93.2% (136/146), clustered into four major
      pulsotypes. Seven sequence types (ST) were identified among the representative
      bovine S. aureus isolates genotyped, including: ST8 (CC8), ST97 (CC97), ST351
      (CC705), ST352 (CC97), ST508 (CC45), ST2992 (CC97) and a novel sequence type,
      ST3538 (CC97). Based on PFGE analysis, greater genetic diversity was observed
      among the human S. aureus isolates. Bovine and human isolates from three sampling
      sites clustered together and were genotypically indistinguishable. Two of the
      isolates, ST97 and ST352 belong to the common bovine lineage CC97, and their
      isolation from close human contacts suggests zoonotic transfer. In the context of
      this study, the third isolate, ST8 (CC8), is believed to be a human clone which
      has transferred to a dairy cow and has subsequently caused mastitis. The
      detection of indistinguishable S. aureus isolates from bovine and human hosts at
      three of the sampling sites is suggestive of bacterial transmission and supports
      the need for vigilant monitoring of staphylococcal populations at the human
      animal interface.

PMID- 28428773
TI  - Mutation at G103 of MtbFtsZ Altered their Sensitivity to Coumarins.
AB  - Coumarins are natural polyphenol lactones comprising of fused rings of benzene
      and alpha-pyrone. The current study demonstrates the inhibitory effect of
      coumarins with various substitutions on Mycobacterium smegmatis mc2 155. We also
      demonstrate the effect of pomegranate (Punica granatum) extract containing
      ellagic acid, on M. smegmatis as well as their affect on MtbFtsZ (FtsZ from
      Mycobacterium tuberculosis). The ellagic acid extracts from pomegranate peels
      inhibit mycobacteria with a MIC of 25 MUM and 0.3 to 3.5 mg/mL, respectively, but
      failed to inhibit the polymerization of MtbFtsZ. However, the coumarins were
      shown to inhibit the polymerization and GTPase activity of the protein as well as
      have an inhibitory affect on M. smegmatis mc2 155. Docking of the most active
      coumarin (7-Dimethyl-4-methyl coumarin with MIC of 38.7 MUM) to the GTP binding
      site suggests that it interacted with the G103 residue. Based on the docking
      results two mutants of varying activity (G103S and G103A) were constructed to
      elucidate the interaction of MtbFtsZ and coumarins. Mutation of G103 with Serine
      (a bulky group) results in an inactive mutant and substitution with alanine
      produces a variant that retains most of the activity of the wild type. There is a
      disruption of the protofilament formation of the MtbFtsZ upon interaction with
      coumarins as demonstrated by TEM. The coumarins increase the length of
      Mycobacteria five times and MtbFtsZ localization is disturbed. The mutant
      proteins altered the GTPase and polymerization activity of coumarins as compared
      to wild type protein. The results here support that coumarins inhibit
      proliferation of Mycobacteria by targeting the assembly of MtbFtsZ and provide
      the possible binding site of coumarins on MtbFtsZ. This study may aid in the
      design of natural products as anti-mycobacterial agents. The currently reported
      GTP analogs for FtsZ are toxic to the human cell lines; natural coumarins
      targeting the GTP binding site of MtbFtsZ may hold promise as an important drug
      lead for tuberculosis treatment.

PMID- 28428774
TI  - Biochar Addition Increases the Rates of Dissimilatory Iron Reduction and
      Methanogenesis in Ferrihydrite Enrichments.
AB  - Biochar contains quinones and aromatic structures that facilitate extracellular
      electron transfer between microbial cells and insoluble minerals. In this study,
      granulated biochar (1.2-2 mm) and powdered biochar (<0.15 mm) were amended to two
      ferrihydrite (in situ ferrihydrite and ex situ ferrihydrite) enrichments to
      investigate the effect of biochar with different particle sizes on dissimilatory
      iron(III)-reducing bacteria (DIRB) and methanogens. Biochar addition
      significantly stimulated the reduction of both in situ ferrihydrite and ex situ
      ferrihydrite and the production of methane. Powdered biochar amendments increased
      iron reduction compared to granulated biochar amendment in both the in situ
      ferrihydrite and ex situ ferrihydrite enrichments. However, no significant
      difference was observed in methane production between the powdered biochar and
      granulated biochar amendments in the two ferrihydrite enrichments. Analysis of
      16S rRNA gene sequences showed that both DIRB and methanogens were enriched after
      biochar amendments in the in situ ferrihydrite and ex situ ferrihydrite
      enrichments. Taxa belonging to the Geobacteraceae and methanogenic genus
      affiliated to Methanosarcina were detected with significantly higher relative
      abundances in powdered biochar amendments than those in granulated biochar
      amendments in both the ferrihydrite enrichments. X-ray diffraction analysis
      indicated green rust [Fe2(CO3) (OH)] and vivianite [Fe3(PO4)2 8(H2O)] formed in
      the ex situ ferrihydrite and in situ ferrihydrite enrichments without biochar
      addition, respectively. After granulated biochar amendment, the mineral phase
      changed from the green rust to vivianite in the ex situ ferrihydrite enrichment,
      while crystalline vivianite and iron oxide (gamma-Fe2O3) were detected
      simultaneously in the in situ ferrihydrite enrichment. No crystalline iron
      compound was found in the powdered biochar amendments in both ferrihydrite
      enrichments. Overall, our study illustrated that the addition of biochar affected
      iron-reducing and methane-generating microbial communities to some extent.

PMID- 28428775
TI  - Genomics Reveals a Unique Clone of Burkholderia cenocepacia Harboring an Actively
      Excising Novel Genomic Island.
AB  - Burkholderia cenocepacia is a clinically dominant form among the other virulent
      species of Burkholderia cepacia complex (Bcc). In the present study, we sequenced
      and analyzed the genomes of seven nosocomial Bcc isolates, five of which were
      isolated from the bloodstream infections and two isolates were recovered from the
      hospital setting during the surveillance. Genome-based species identification of
      the Bcc isolates using a type strain explicitly identified the species as B.
      cenocepacia. Moreover, single nucleotide polymorphism analysis revealed that the
      six isolates were clonal and phylogenetically distinct from the other B.
      cenocepacia. Comparative genomics distinctly revealed the larger genome size of
      six clonal isolates as well as the presence of a novel 107 kb genomic island
      named as BcenGI15, which encodes putative pathogenicity-associated genes. We have
      shown that the BcenGI15 has an ability to actively excise from the genome and
      forming an extrachromosomal circular form suggesting its mobile nature.
      Surprisingly, a homolog of BcenGI15 was also present in the genome of a clinical
      isolate named Burkholderia pseudomallei strain EY1. This novel genetic element is
      present only in the variants of B. cenocepacia and B. pseudomallei isolates
      suggesting its interspecies existence in the main pathogenic species of the genus
      Burkholderia. In conclusion, the whole genome analysis of the genomically
      distinct B. cenocepacia clinical isolates has advanced our understanding of the
      epidemiology and evolution of this important nosocomial pathogen as well as its
      relatives.

PMID- 28428776
TI  - Mapping and Identification of Antifungal Peptides in the Putative Antifungal
      Protein AfpB from the Filamentous Fungus Penicillium digitatum.
AB  - Antifungal proteins (AFPs) from Ascomycetes are small cysteine-rich proteins that
      are abundantly secreted and show antifungal activity against non-producer fungi.
      A gene coding for a class B AFP (AfpB) was previously identified in the genome of
      the plant pathogen Penicillium digitatum. However, previous attempts to detect
      the AfpB protein were not successful despite the high expression of the
      corresponding afpB gene. In this work, the structure of the putative AfpB was
      modeled. Based on this model, four synthetic cysteine-containing peptides,
      PAF109, PAF112, PAF118, and PAF119, were designed and their antimicrobial
      activity was tested and characterized. PAF109 that corresponds to the gamma-core
      motif present in defensin-like antimicrobial proteins did not show antimicrobial
      activity. On the contrary, PAF112 and PAF118, which are cationic peptides derived
      from two surface-exposed loops in AfpB, showed moderate antifungal activity
      against P. digitatum and other filamentous fungi. It was also confirmed that
      cyclization through a disulfide bridge prevented peptide degradation. PAF116,
      which is a peptide analogous to PAF112 but derived from the Penicillium
      chrysogenum antifungal protein PAF, showed activity against P. digitatum similar
      to PAF112, but was less active than the native PAF protein. The two AfpB-derived
      antifungal peptides PAF112 and PAF118 showed positive synergistic interaction
      when combined against P. digitatum. Furthermore, the synthetic hexapeptide PAF26
      previously described in our laboratory also exhibited synergistic interaction
      with the peptides PAF112, PAF118, and PAF116, as well as with the PAF protein.
      This study is an important contribution to the mapping of antifungal motifs
      within the AfpB and other AFPs, and opens up new strategies for the rational
      design and application of antifungal peptides and proteins.

PMID- 28428777
TI  - Lactobacillus fermentum Postbiotic-induced Autophagy as Potential Approach for
      Treatment of Acetaminophen Hepatotoxicity.
AB  - The aim of this study was to investigate the potential of postbiotics originated
      from Lactobacillus fermentum BGHV110 strain (HV110) to counteract acetaminophen
      (APAP)-induced hepatotoxicity in HepG2 cells. This strain was selected according
      to its autophagy inducing potential, based on previous studies reporting
      protective role of autophagy in APAP caused cellular damage. Cell viability was
      assessed using MTT and LDH assays, while autophagy was monitored by qPCR analysis
      of BECN1, Atg5, p62/SQSTM1, and PINK1 mRNA expression and by Western blot
      analysis of p62/SQSTM1 and lipidated LC3 accumulation. Our results showed that
      detrimental effect of APAP on cell viability was suppressed in the presence of
      HV110 which was linked with increased conversion of LC3 protein and p62/SQSTM1
      protein degradation. Additionally, higher p62/SQSTM1 and PINK1 mRNA transcription
      were noticed in cells co-treated with APAP/HV110, simultaneously. In conclusion,
      this study suggests that HV110 enhances activation of PINK1-dependent autophagy
      in HepG2 cells and its eventual co-supplementation with APAP could be potentially
      used for alleviation of hepatotoxic side effects caused by APAP overdose.

PMID- 28428778
TI  - Evidence for Nitric Oxide Synthase Activity in Staphylococcus xylosus Mediating
      Nitrosoheme Formation.
AB  - Staphylococcus xylosus is used as a starter culture in fermented meat products
      and contributes to color formation by the reduction of nitrate to nitrite.
      Nitrite is a food additive that is chemically turned to nitric oxide (NO) in meat
      but its safety has been questioned. The objective of this study was to determine
      the ability of NO synthase (NOS) of S. xylosus C2a to produce NO. For this
      purpose, a nos deletion mutant (Deltanos) in S. xylosus was constructed and NO
      production was evaluated in a test based on its ability to form nitrosomyoglobin
      and nitrosoheme. Production of NO was abrogated in the Deltanos mutant under
      aerobic conditions and reduced about 35-40% comparing to the wild type C2a under
      limited oxygenation. This mutant was sensitive to oxidative stress. The
      expression of genes encoding catalase was modulated in the mutant with an up
      regulation of katA and a down-regulation of katB and katC. The Deltanos mutant
      displayed high colony pigmentation after prolonged growth on agar medium.
      Finally, the Deltanos mutant showed no growth in minimal medium. Growth was not
      restored in the minimal medium by complementation with nos, but was restored by
      either addition of phenylalanine or complementation with pdt, a gene that encodes
      a prephenate dehydratase involved in phenylalanine biosynthesis and co
      transcribed with nos. Our findings clearly demonstrate NOS-mediated NO production
      in S. xylosus, a meat-associated coagulase-negative Staphylococcus.

PMID- 28428779
TI  - Application of beta-Resorcylic Acid as Potential Antimicrobial Feed Additive to
      Reduce Campylobacter Colonization in Broiler Chickens.
AB  - Campylobacter is one of the major foodborne pathogens that result in severe
      gastroenteritis in humans, primarily through consumption of contaminated poultry
      products. Chickens are the reservoir host of Campylobacter, where the pathogen
      colonizes the ceca, thereby leading to contamination of carcass during slaughter.
      A reduction in cecal colonization by Campylobacter would directly translate into
      reduced product contamination and risk of human infections. With increasing
      consumer demand for antibiotic free chickens, significant research is being
      conducted to discover natural, safe and economical antimicrobials that can
      effectively control Campylobacter colonization in birds. This study investigated
      the efficacy of in-feed supplementation of a phytophenolic compound, beta
      resorcylic acid (BR) for reducing Campylobacter colonization in broiler chickens.
      In two separate, replicate trials, day-old-chicks (Cobb500; n = 10
      birds/treatment) were fed with BR (0, 0.25, 0.5, or 1%) in feed for a period of
      14 days (n = 40/trial). Birds were challenged with a four-strain mixture of
      Campylobacter jejuni (~106 CFU/ml; 250 MUl/bird) on day 7 and cecal samples were
      collected on day 14 for enumerating surviving Campylobacter in cecal contents. In
      addition, the effect of BR on the critical colonization factors of Campylobacter
      (motility, epithelial cell attachment) was studied using phenotypic assay, cell
      culture, and real-time quantitative PCR. Supplementation of BR in poultry feed
      for 14 days at 0.5 and 1% reduced Campylobacter populations in cecal contents by
      ~2.5 and 1.7 Log CFU/g, respectively (P < 0.05). No significant differences in
      feed intake and body weight gain were observed between control and treatment
      birds fed the compound (P > 0.05). Follow up mechanistic analysis revealed that
      sub-inhibitory concentration of BR significantly reduced Campylobacter motility,
      attachment to and invasion of Caco-2 cells. In addition, the expression of C.
      jejuni genes coding for motility (motA, motB, fliA) and attachment (jlpA, ciaB)
      was down-regulated as compared to controls (P < 0.05). These results suggest that
      BR could potentially be used as a feed additive to reduce Campylobacter
      colonization in broilers.

PMID- 28428780
TI  - Genomic and Transcriptomic Insights into Calcium Carbonate Biomineralization by
      Marine Actinobacterium Brevibacterium linens BS258.
AB  - Calcium carbonate (CaCO3) biomineralization has been investigated due to its wide
      range of scientific and technological implications, however, the molecular
      mechanisms of this important geomicrobiological process are largely unknown.
      Here, a urease-positive marine actinobacterium Brevibacterium linens BS258 was
      demonstrated to effectively form CaCO3 precipitates. Surprisingly, this bacterium
      could also dissolve the formed CaCO3 with the increase of the Ca2+ concentration.
      To disclose the mechanisms of biomineralization, the genome of B. linens BS258
      was further completely sequenced. Interestingly, the expression of three carbonic
      anhydrases was significantly up-regulated along with the increase of Ca2+
      concentration and the extent of calcite dissolution. Moreover, transcriptome
      analyses revealed that increasing concentration of Ca2+ induced KEGG pathways
      including quorum sensing (QS) in B. linens BS258. Notably, most up-regulated
      genes related to QS were found to encode peptide/nickel ABC transporters, which
      suggested that nickel uptake and its associated urease stimulation were essential
      to boost CaCO3 biomineralization. Within the genome of B. linens BS258, there are
      both cadmium and lead resistance gene clusters. Therefore, the sequestration
      abilities of Cd2+ and Pb2+ by B. linens BS258 were checked. Consistently, Pb2+
      and Cd2+ could be effectively sequestered with the precipitation of calcite by B.
      linens BS258. To our knowledge, this is the first study investigating the
      microbial CaCO3 biomineralization from both genomic and transcriptomic insights,
      which paves the way to disclose the relationships among bacterial metabolisms and
      the biomineralization.

PMID- 28428781
TI  - Analysis of the Listeria monocytogenes Population Structure among Isolates from
      1931 to 2015 in Australia.
AB  - Listeriosis remains among the most important bacterial illnesses, with a high
      associated mortality rate. Efforts to control listeriosis require detailed
      knowledge of the epidemiology of the disease itself, and its etiological
      bacterium, Listeria monocytogenes. In this study we provide an in-depth analysis
      of the epidemiology of 224 L. monocytogenes isolates from Australian clinical and
      non-clinical sources. Non-human sources included meat, dairy, seafood, fruit, and
      vegetables, along with animal and environmental isolates. Serotyping, Multi-Locus
      Sequence Typing, and analysis of inlA gene sequence were performed. Serogroups
      IIA, IIB, and IVB comprised 94% of all isolates, with IVB over-represented among
      clinical isolates. Serogroup IIA was the most common among dairy and meat
      isolates. Lineage I isolates were most common among clinical isolates, and 52% of
      clinical isolates belonged to ST1. Overall 39 STs were identified in this study,
      with ST1 and ST3 containing the largest numbers of L. monocytogenes isolates.
      These STs comprised 40% of the total isolates (n = 90), and both harbored
      isolates from clinical and non-clinical sources. ST204 was the third most common
      ST. The high prevalence of this group among L. monocytogenes populations has not
      been reported outside Australia. Twenty-seven percent of the STs in this study
      contained exclusively clinical isolates. Analysis of the virulence protein InlA
      among isolates in this study identified a truncated form of the protein among
      isolates from ST121 and ST325. The ST325 group contained a previously unreported
      novel mutation leading to production of a 93 amino acid protein. This study
      provides insights in the population structure of L. monocytogenes isolated in
      Australia, which will contribute to public health knowledge relating to this
      important human pathogen.

PMID- 28428782
TI  - A Recombinant Potato virus Y Infectious Clone Tagged with the Rosea1 Visual
      Marker (PVY-Ros1) Facilitates the Analysis of Viral Infectivity and Allows the
      Production of Large Amounts of Anthocyanins in Plants.
AB  - Potato virus Y (PVY) is a major threat to the cultivation of potato and other
      solanaceous plants. By inserting a cDNA coding for the Antirrhinum majus Rosea1
      transcription factor into a PVY infectious clone, we created a biotechnological
      tool (PVY-Ros1) that allows infection by this relevant plant virus to be tracked
      by the naked eye with no need for complex instrumentation. Rosea1 is an MYB-type
      transcription factor whose expression activates the biosynthesis of anthocyanin
      pigments in a dose-specific and cell-autonomous manner. Our experiments showed
      that the mechanical inoculation of solanaceous plants with PVY-Ros1 induced the
      formation of red infection foci in inoculated tissue and solid dark red
      pigmentation in systemically infected tissue, which allows disease progression to
      be easily monitored. By using silver nanoparticles, a nanomaterial with exciting
      antimicrobial properties, we proved the benefits of PVY-Ros1 to analyze novel
      antiviral treatments in plants. PVY-Ros1 was also helpful for visually monitoring
      the virus transmission process by an aphid vector. Most importantly, the
      anthocyanin analysis of infected tobacco tissues demonstrated that PVY-Ros1 is an
      excellent biotechnological tool for molecular farming because it induces the
      accumulation of larger amounts of anthocyanins, antioxidant compounds of
      nutritional, pharmaceutical and industrial interest, than those that naturally
      accumulate in some fruits and vegetables well known for their high anthocyanin
      content. Hence these results support the notion that the virus-mediated
      expression of regulatory factors and enzymes in plants facilitates easy quick
      plant metabolism engineering.

PMID- 28428783
TI  - Corrigendum: Effects of Short-Term Warming and Altered Precipitation on Soil
      Microbial Communities in Alpine Grassland of the Tibetan Plateau.
AB  - [This corrects the article on p. 1032 in vol. 7, PMID: 27446064.].

PMID- 28428784
TI  - The Roles of Mast Cells in Parasitic Protozoan Infections.
AB  - Protozoan parasites such as Plasmodium spp., Leishmania spp., Trypanosoma spp.,
      and Toxoplasma gondii are major causes of parasitic diseases in both humans and
      animals. The immune system plays a critical role against protozoa, but their
      immune mechanism remains poorly understood. This highlights the need to
      investigate the function of immune cells involved in the process of parasite
      infections and the responses of host immune system to parasite infections. Mast
      cells (MCs) are known to be central players in allergy and anaphylaxis, and it
      has been demonstrated that MCs have crucial roles in host defense against a
      number of different pathogens, including parasites. To date, there are many
      studies that have examined the interaction of helminth-derived antigens and MCs.
      As one of the major effector cells, MCs also play an important role in the immune
      response against some parasitic protozoa, but their role in protozoan infections
      is, however, less well characterized. Herein, we review the current knowledge
      about the roles of MCs and their mediators during infections involving highly
      pathogenic protozoa including Plasmodium spp., Leishmania spp., Trypanosoma spp.,
      and T. gondii. We offer a general review of the data from patients and
      experimental animal models infected with the aforementioned protozoa, which
      correlate MCs and MC-derived mediators with exacerbated inflammation and disease
      progression as well as protection against the parasitic infections in different
      circumstances. This review updates our current understanding of the roles of MCs
      during parasitic protozoan infections, and the participation of MCs in parasitic
      protozoan infections could be of a potential therapeutic target.

PMID- 28428785
TI  - Interferon Gamma Induces Changes in Natural Killer (NK) Cell Ligand Expression
      and Alters NK Cell-Mediated Lysis of Pediatric Cancer Cell Lines.
AB  - Natural killer (NK) cells have therapeutic potential for cancer due to their
      capacity for targeting tumor cells without prior sensitization. Our laboratory
      has developed an NK cell expansion protocol that generates large quantities of NK
      cells for therapeutic infusion that secret 20 times the amount of interferon
      gamma (IFNgamma) than resting NK cells. IFNgamma can upregulate major
      histocompatibility complex (MHC)-class I, an inhibitory ligand for NK cells, but
      can also upregulate intercellular adhesion molecule 1 (ICAM-1) which promotes
      NK:target cell interaction for an efficient lysis. Due to the opposing effects
      reported for IFNgamma on tumor sensitivity to NK cells, we evaluated a panel 22
      tumor cell lines from the pediatric preclinical testing program corresponding to
      different tumor types. We determined the impact of IFNgamma on their expression
      of NK cell activating and inhibitory ligands, death receptors, and adhesion
      molecules using mass cytometry. We also evaluated the effect of IFNgamma on their
      sensitivity to NK cell-mediated lysis. Our results show upregulation of PD-L1,
      ICAM-1, MHC-class I, HLA-DR, CD95/FasR, and CD270/HVEM after IFNgamma treatment,
      this upregulation is variable across different tumor types. We also observed a
      variable impact of IFNgamma in NK cell-mediated lysis. For six of the cancer cell
      lines IFNgamma resulted in increased resistance to NK cells, while for three of
      them it resulted in increased sensitivity. Modeling of the data suggests that the
      effect of IFNgamma on NK cell-mediated tumor lysis is mostly dependent on changes
      in MHC-class I and ICAM-1 expression. For three of the cell lines with increased
      resistance, we observed higher upregulation of MHC-class I than ICAM-1. For the
      cell lines with increased sensitivity after IFNgamma treatment, we observed
      upregulation of ICAM-1 exceeding MHC-class I upregulation. ICAM-1 upregulation
      resulted in increased conjugate formation between the NK cells and tumor cells,
      which can contribute to the increased sensitivity observed. However, the effects
      of MHC-class I and ICAM-1 are not readily predictable. Due to the high IFNgamma
      secretion of NK cell infusion products, a better understanding of the NK ligands
      on tumor cells and how they are affected by IFNgamma is essential to optimize NK
      cell immunotherapy.

PMID- 28428786
TI  - Challenge of Humans with Wild-type Salmonella enterica Serovar Typhi Elicits
      Changes in the Activation and Homing Characteristics of Mucosal-Associated
      Invariant T Cells.
AB  - Gastrointestinal infections by Salmonella enterica serovar Typhi (S. Typhi) are
      rare in industrialized countries. However, they remain a major public health
      problem in the developing world with an estimated 26.9 million new cases annually
      and significant mortality when untreated. Recently, we provided the first direct
      evidence that CD8+ MAIT cells are activated and have the potential to kill cells
      exposed to S. Typhi, and that these responses are dependent on bacterial load.
      However, MAIT cell kinetics and function during bacterial infections in humans
      remain largely unknown. In this study, we characterize the human CD8+ MAIT cell
      immune response to S. Typhi infection in subjects participating in a challenge
      clinical trial who received a low- or high dose of wild-type S. Typhi. We define
      the kinetics of CD8+ MAIT cells as well as their levels of activation,
      proliferation, exhaustion/apoptosis, and homing potential. Regardless of the
      dose, in volunteers resistant to infection (NoTD), the levels of CD8+ MAIT cells
      after S. Typhi challenge fluctuated around their baseline values (day 0). In
      contrast, volunteers susceptible to the development of typhoid disease (TD)
      exhibited a sharp decline in circulating MAIT cells during the development of
      typhoid fever. Interestingly, MAIT cells from low-dose TD volunteers had higher
      levels of CD38 coexpressing CCR9, CCR6, and Ki67 during the development of
      typhoid fever than high-dose TD volunteers. No substantial perturbations on the
      levels of these markers were observed in NoTD volunteers irrespective of the
      dose. In sum, we describe, for the first time, that exposure to an enteric
      bacterium, in this case S. Typhi, results in changes in MAIT cell activation,
      proliferation, and homing characteristics, suggesting that MAIT cells are an
      important component of the human host response to bacterial infection.

PMID- 28428787
TI  - A Possible Role for Idiotype/Anti-idiotype B-T Cell Interactions in Maintaining
      Immune Memory.
AB  - Variable regions of both B-cell receptors (BCRs) and T-cell receptors (TCRs) are
      completely formed in the postnatal period, and, consequently, no innate immune
      tolerance against these structures exists in adulthood. Indeed, antibodies (Abs)
      specific to TCRs have been found in both animals and humans. These facts clearly
      indicate the existence of B cells able to directly interact with T cells through
      binding of BCRs to TCRs without implicating major histocompatibility complex
      molecules. A novel paradigm is proposed in that the immune memory is based on
      idiotype/anti-idiotype interactions occurring between BCRs and TCRs following
      clearance of the antigen that elicited immune responses. It is envisaged that
      direct contact between memory T and B cells could provide co-stimulatory signals
      needed to sustain viability, growth, and differentiation of the interacting
      immune cells. In contrast, plasma cells originating from memory B-cells could
      produce anti-TCR Abs that inhibit direct BCR-to-TCR interactions, thereby
      downregulating the B- to T-cell contact-based immune memory via a negative
      feedback mechanism.

PMID- 28428790
TI  - Nanoparticle Interactions with the Immune System: Clinical Implications for
      Liposome-Based Cancer Chemotherapy.
AB  - The development of stable and long-circulating liposomes provides protection of
      the drug cargo from degradation and increases tumor drug delivery, leading to the
      design of liposome formulations with great potential in cancer therapy. However,
      despite the sound pharmacologic basis, many liposomal as well as other
      nanoparticle-based drug formulations have failed to meet regulatory criteria for
      approval. The question that arises is whether we have missed key liposome-host
      interactions that can account for the gap between the major pharmacologic
      advantages in preclinical studies and the modest impact of the clinical effects
      in humans. We will discuss here the nanoparticle-immune system interactions that
      may undermine the antitumor effect of the nanodrug formulations and contribute to
      this gap. To overcome this challenge and increase clinical translation, new
      preclinical models need to be adopted along with comprehensive
      immunopharmacologic studies and strategies for patient selection in the clinical
      phase.

PMID- 28428789
TI  - IL-10-Producing B Cells Regulate T Helper Cell Immune Responses during 1,3-beta
      Glucan-Induced Lung Inflammation.
AB  - With the rapid development of industry and farm, fungi contamination widely
      exists in occupational environment. Inhalation of fungi-contaminated organic dust
      results in hypersensitivity pneumonitis. 1,3-beta-Glucan is a major cell wall
      component of fungus and is considered as a biomarker of fungi exposure. Current
      studies showed that 1,3-beta-glucan exposure induced lung inflammation, which
      involved uncontrolled T helper (Th) cell immune responses, such as Th1, Th2,
      Th17, and regulatory T cell (Treg). A recently identified IL-10-producing B cells
      (B10) was reported in regulating immune homeostasis. However, its regulatory role
      in hypersensitivity pneumonitis is still subject to debate. In our study, we
      comprehensively investigated the role of B10 and the relationship between B10 and
      Treg in 1,3-beta-glucan-induced lung inflammation. Mice with insufficient B10
      exhibited more inflammatory cells accumulation and severer pathological
      inflammatory changes. Insufficient B10 led to increasing Th1, Th2, and Th17
      responses and restricted Treg function. Depletion of Treg before the onset of
      inflammation could suppress B10. Whereas, Treg depletion only at the late stage
      of inflammation failed to affect B10. Our study demonstrated that insufficient
      B10 aggravated the lung inflammation mediated by dynamic shifts in Th immune
      responses after 1,3-beta-glucan exposure. The regulatory function of B10 on Th
      immune responses might be associated with Treg and IL-10. Treg could only
      interact with B10 at an early stage.

PMID- 28428788
TI  - The Protective Role of Type I Interferons in the Gastrointestinal Tract.
AB  - The immune system of the gastrointestinal (GI) tract manages the significant task
      of recognizing and eliminating pathogens while maintaining tolerance of commensal
      bacteria. Dysregulation of this delicate balance can be detrimental, resulting in
      severe inflammation, intestinal injury, and cancer. Therefore, mechanisms to
      relay important signals regulating cell growth and immune reactivity must be in
      place to support GI homeostasis. Type I interferons (IFN-I) are a family of
      pleiotropic cytokines, which exert a wide range of biological effects including
      promotion of both pro- and anti-inflammatory activities. Using animal models of
      colitis, investigations into the regulation of intestinal epithelium inflammation
      highlight the role of IFN-I signaling during fine modulation of the immune
      system. The intestinal epithelium of the gut guides the immune system to
      differentiate between commensal and pathogenic microbiota, which relies on
      intimate links with the IFN-I signal-transduction pathway. The current paradigm
      depicts an IFN-I-induced antiproliferative state in the intestinal epithelium
      enabling cell differentiation, cell maturation, and proper intestinal barrier
      function, strongly supporting its role in maintaining baseline immune activity
      and clearance of damaged epithelia or pathogens. In this review, we will
      highlight the importance of IFN-I in intestinal homeostasis by discussing its
      function in inflammation, immunity, and cancer.

PMID- 28428791
TI  - Genome-Wide Association Study for Pre-harvest Sprouting Resistance in a Large
      Germplasm Collection of Chinese Wheat Landraces.
AB  - Pre-harvest sprouting (PHS) is mainly caused by the breaking of seed dormancy in
      high rainfall regions, which leads to huge economic losses in wheat. In this
      study, we evaluated 717 Chinese wheat landraces for PHS resistance and carried
      out genome-wide association studies (GWAS) using to 9,740 DArT-seq and 178,803
      SNP markers. Landraces were grown across six environments in China and
      germination testing of harvest-ripe grain was used to calculate the germination
      rate (GR) for each accession at each site. GR was highly correlated across all
      environments. A large number of landraces (194) displayed high levels of PHS
      resistance (i.e., mean GR < 0.20), which included nine white-grained accessions.
      Overall, white-grained accessions displayed a significantly higher mean GR (42.7
      79.6%) compared to red-grained accessions (19.1-56.0%) across the six
      environments. Landraces from mesic growing zones in southern China showed higher
      levels of PHS resistance than those sourced from xeric areas in northern and
      north-western China. Three main quantitative trait loci (QTL) were detected by
      GWAS: one on 5D that appeared to be novel and two co-located with the grain color
      transcription factor Tamyb10 on 3A and 3D. An additional 32 grain color related
      QTL (GCR-QTL) were detected when the set of red-grained landraces were analyzed
      separately. GCR-QTL occurred at high frequencies in the red-grained accessions
      and a strong correlation was observed between the number of GCR-QTL and GR (R2 =
      0.62). These additional factors could be critical for maintaining high levels of
      PHS resistance and represent targets for introgression into white-grained wheat
      cultivars. Further, investigation of the origin of haplotypes associated with the
      three main QTL revealed that favorable haplotypes for PHS resistance were more
      common in accessions from higher rainfall zones in China. Thus, a combination of
      natural and artificial selection likely resulted in landraces incorporating PHS
      resistance in China.

PMID- 28428792
TI  - Identification of Candidate Genes and Biosynthesis Pathways Related to Fertility
      Conversion by Wheat KTM3315A Transcriptome Profiling.
AB  - The Aegilops kotschyi thermo-sensitive cytoplasmic male sterility (K-TCMS) system
      may facilitate hybrid wheat (Triticum aestivum L.) seed multiplication and
      production. The K-TCMS line is completely male sterile during the normal wheat
      growing season, whereas its fertility can be restored in a high-temperature
      environment. To elucidate the molecular mechanisms responsible for male
      sterility/fertility conversion and candidate genes involved with pollen
      development in K-TCMS, we employed RNA-seq to sequence the transcriptomes of
      anthers from K-TCMS line KTM3315A during development under sterile and fertile
      conditions. We identified 16840 differentially expressed genes (DEGs) in
      different stages including15157 known genes (15135 nuclear genes and 22
      plasmagenes) and 1683 novel genes. Bioinformatics analysis identified possible
      metabolic pathways involved with fertility based on KEGG pathway enrichment of
      the DEGs expressed in fertile and sterile plants. We found that most of the genes
      encoding key enzyme in the phenylpropanoid biosynthesis and jasmonate
      biosynthesis pathways were significant upregulated in uninucleate, binuclate or
      trinucleate stage, which both interact with MYB transcription factors, and that
      link between all play essential roles in fertility conversion. The relevant DEGs
      were verified by quantitative RT-PCR. Thus, we suggested that phenylpropanoid
      biosynthesis and jasmonate biosynthesis pathways were involved in fertility
      conversion of K-TCMS wheat. This will provide a new perspective and an effective
      foundation for the research of molecular mechanisms of fertility conversion of
      CMS wheat. Fertility conversion mechanism in thermo-sensitive cytoplasmic male
      sterile/fertile wheat involves the phenylpropanoid biosynthesis pathway,
      jasmonate biosynthesis pathway, and MYB transcription factors.

PMID- 28428793
TI  - Transcriptomics, Targeted Metabolomics and Gene Expression of Blackberry Leaves
      and Fruits Indicate Flavonoid Metabolic Flux from Leaf to Red Fruit.
AB  - Blackberries (Rubus spp.) are among the high added value food products relevant
      for human health due to the increasing evidence of the beneficial effects of
      polyphenols, which are very abundant in these fruits. Interestingly, these
      compounds also play a role on plant physiology, being especially relevant their
      role in plant defense against biotic and abiotic stress. Hence, we hypothesize
      that since blackberry fruits have high amounts of flavonols and anthocyanins,
      leaves would also have high amounts of these compounds, and can be studied as a
      source of active molecules; furthermore, leaf synthesis would support their high
      contents in fruits. To explore this hypothesis, the present study reports a de
      novo transcriptome analysis on field grown blackberry leaves and fruits at the
      same time point, to establish the metabolic relationship of these compounds in
      both organs. Transcripts were aligned against Fragaria vesca genome, and genes
      were identified and annotated in different databases; tissue expression pattern
      showed 20,463 genes common to leaves and fruits, while 6,604 genes were
      significantly overexpressed only in fruits, while another 6,599 genes were
      significantly overexpressed in leaves, among which flavonol-anthocyanin
      transporter genes were present. Bioactives characterization indicated that total
      phenolics in leaves were three-fold, and flavonols were six-fold than in fruits,
      while concentration of anthocyanins was higher in fruits; HPLC-MS analysis
      indicated different composition in leaves and fruits, with cyanidin-3-glucoside
      as the only common compound identified. Next, RT-qPCR of the core genes in the
      flavonol anthocyanin pathway and regulatory MYB genes were carried out.
      Interestingly, genes in the flavonol-anthocyanin pathway and flavonol-transport
      families were overexpressed in leaves, consistent with the higher bioactive
      levels. On the other hand, transcription factors were overexpressed in fruits
      anticipating an active anthocyanin biosynthesis upon ripening. This suggests
      that, in addition to the biosynthesis taking place in the fruits during ripening,
      translocation of flavonols from leaves to fruits contributes to the high amounts
      of bioactives starting to accumulate in fruits.

PMID- 28428794
TI  - Fine Mapping of a Novel defective glume 1 (dg1) Mutant, Which Affects Vegetative
      and Spikelet Development in Rice.
AB  - In cereal crops, vegetative and spikelet development play important roles in
      grain yield and quality, but the genetic mechanisms that control vegetative and
      spikelet development remain poorly understood in rice. Here, we identified a new
      rice mutant, defective glume 1 (dg1) mutant from cultivar Zhonghua11 after ethyl
      methanesulfonate treatment. The dg1 mutant displayed the dwarfism with small,
      rolled leaves, which resulted from smaller cells and more bulliform cells. The
      dg1 mutant also had an enlarged leaf angle and defects in brassinosteroid
      signaling. In the dg1 mutant, both the rudimentary glume and sterile lemma
      (glumes) were transformed into lemma-like organ and acquired the lemma identity.
      Additionally, the dg1 mutant produced slender grains. Further analysis revealed
      that DG1 affects grain size by regulating cell proliferation and expansion. We
      fine mapped the dg1 locus to a 31-kb region that includes eight open reading
      frames. We examined the DNA sequence and expression of these loci, but we were
      not able to identify the DG1 gene. Therefore, more work will be needed for
      cloning and functional analysis of DG1, which would contribute to our
      understanding of the molecular mechanisms behind whole-plant development in rice.

PMID- 28428796
TI  - Expression Profiling Coupled with In-silico Mapping Identifies Candidate Genes
      for Reducing Aflatoxin Accumulation in Maize.
AB  - Aflatoxin, produced by Aspergillus flavus, is hazardous to health of humans and
      livestock. The lack of information about large effect QTL for resistance to
      aflatoxin accumulation is a major obstacle to employ marker-assisted selection
      for maize improvement. The understanding of resistance mechanisms of the host
      plant and the associated genes is necessary for improving resistance to A. flavus
      infection. A suppression subtraction hybridization (SSH) cDNA library was made
      using the developing kernels of Mp715 (resistant inbred) and B73 (susceptible
      inbred) and 480 randomly selected cDNA clones were sequenced to identify
      differentially expressed genes (DEGs) in response to A. flavus infection and map
      these clones onto the corn genome by in-silico mapping. A total of 267 unigenes
      were identified and majority of genes were related to metabolism, stress
      response, and disease resistance. Based on the reverse northern hybridization
      experiment, 26 DEGs were selected for semi-quantitative RT-PCR analysis in seven
      inbreds with variable resistance to aflatoxin accumulation at two time points
      after A. flavus inoculation. Most of these genes were highly expressed in
      resistant inbreds. Quantitative RT-PCR analysis validated upregulation of PR-4,
      DEAD-box RNA helicase, and leucine rich repeat family protein in resistant
      inbreds. Fifty-six unigenes, which were placed on linkage map through in-silico
      mapping, overlapped the QTL regions for resistance to aflatoxin accumulation
      identified in a mapping population derived from the cross between B73 and Mp715.
      Since majority of these mapped genes were related to disease resistance, stress
      response, and metabolism, these should be ideal candidates to investigate host
      pathogen interaction and to reduce aflatoxin accumulation in maize.

PMID- 28428797
TI  - Silicon Regulates Antioxidant Activities of Crop Plants under Abiotic-Induced
      Oxidative Stress: A Review.
AB  - Silicon (Si) is the second most abundant element in soil, where its availability
      to plants can exhilarate to 10% of total dry weight of the plant. Si
      accumulation/transport occurs in the upward direction, and has been identified in
      several crop plants. Si application has been known to ameliorate plant growth and
      development during normal and stressful conditions over past two-decades. During
      abiotic (salinity, drought, thermal, and heavy metal etc) stress, one of the
      immediate responses by plant is the generation of reactive oxygen species (ROS),
      such as singlet oxygen (1O2), superoxide ([Formula: see text]), hydrogen peroxide
      (H2O2), and hydroxyl radicals (OH), which cause severe damage to the cell
      structure, organelles, and functions. To alleviate and repair this damage, plants
      have developed a complex antioxidant system to maintain homeostasis through non
      enzymatic (carotenoids, tocopherols, ascorbate, and glutathione) and enzymatic
      antioxidants [superoxide dismutase (SOD), catalase (CAT), and ascorbate
      peroxidase (APX)]. To this end, the exogenous application of Si has been found to
      induce stress tolerance by regulating the generation of ROS, reducing
      electrolytic leakage, and malondialdehyde (MDA) contents, and immobilizing and
      reducing the uptake of toxic ions like Na, under stressful conditions. However,
      the interaction of Si and plant antioxidant enzyme system remains poorly
      understood, and further in-depth analyses at the transcriptomic level are needed
      to understand the mechanisms responsible for the Si-mediated regulation of stress
      responses.

PMID- 28428798
TI  - Plastic-Film Mulching for Enhanced Water-Use Efficiency and Economic Returns from
      Maize Fields in Semiarid China.
AB  - Film mulch has gradually been popularized to increase water availability to crops
      for improving and stabilizing agricultural production in the semiarid areas of
      Northwest China. To find more sustainable and economic film mulch methods for
      alleviating drought stress in semiarid region, it is necessary to test optimum
      planting methods in same cultivation conditions. A field experiment was conducted
      during 2013 and 2014 to evaluate the effects of different plastic film mulch
      methods on soil water, soil temperature, water use efficiency (WUE), yield and
      revenue. The treatments included: (i) the control, conventional flat planting
      without plastic film mulch (CK); (ii) flat planting with maize rows (60 cm
      spacing) on plastic film mulch (70 cm wide); (iii) furrow planting of maize (60
      cm spacing), separated by consecutive plastic film-mulched ridges (each 50 cm
      wide and 15 cm tall); (iv) furrow planting of maize (60 cm spacing), separated by
      alternating large and small plastic film-mulched ridges (large ridges: 70 cm wide
      and 15 cm tall, small ridges 50 cm wide and 10 cm tall); and (v) furrow-flat
      planting of maize (60 cm spacing) with a large plastic film-mulched ridge (60 cm
      wide and 15 cm tall) alternating with a flat without plastic film-mulched space
      (60 cm wide). Topsoil temperature (5-25 cm) was significantly (p < 0.05) higher
      in field plots with plastic film mulch than the control (CK), and resulted in
      greater soil water storage (0-200 cm) up to 40 days after planting. Maize grain
      yield and WUE were significantly (p < 0.05) higher with the furrow planting
      methods (consecutive film-mulched ridges and alternating film-mulched ridges)
      than the check in both years. Maize yield was, on average, 29% (p < 0.05) greater
      and 28% (p < 0.05) greater with these furrow planting methods, while the average
      WUE increased by 22.8% (p < 0.05) with consecutive film-mulched ridges and 21.1%
      (p < 0.05) with alternating film-mulched ridges. The 2-year average net income
      increased by 1559, 528, and 350 Chinese Yuan (CNY) ha-1 with the consecutive film
      mulched ridges, furrow-flat planting and alternating film-mulched ridges,
      respectively, compared with the control (CK). We conclude that the consecutive
      film-mulched ridge method was the most productive and profitable for maize in
      this semi-arid area with limited and erratic precipitation.

PMID- 28428795
TI  - Non-canonical Translation in Plant RNA Viruses.
AB  - Viral protein synthesis is completely dependent upon the host cell's
      translational machinery. Canonical translation of host mRNAs depends on
      structural elements such as the 5' cap structure and/or the 3' poly(A) tail of
      the mRNAs. Although many viral mRNAs are devoid of one or both of these
      structures, they can still translate efficiently using non-canonical mechanisms.
      Here, we review the tools utilized by positive-sense single-stranded (+ss) RNA
      plant viruses to initiate non-canonical translation, focusing on cis-acting
      sequences present in viral mRNAs. We highlight how these elements may interact
      with host translation factors and speculate on their contribution for achieving
      translational control. We also describe other translation strategies used by
      plant viruses to optimize the usage of the coding capacity of their very compact
      genomes, including leaky scanning initiation, ribosomal frameshifting and stop
      codon readthrough. Finally, future research perspectives on the unusual
      translational strategies of +ssRNA viruses are discussed, including parallelisms
      between viral and host mRNAs mechanisms of translation, particularly for host
      mRNAs which are translated under stress conditions.

PMID- 28428799
TI  - A Novel Cytoplasmic Male Sterility in Brassica napus (inap CMS) with Carpelloid
      Stamens via Protoplast Fusion with Chinese Woad.
AB  - A novel cytoplasmic male sterility (CMS) in Brassica napus (inap CMS) was
      selected from the somatic hybrid with Isatis indigotica (Chinese woad) by
      recurrent backcrossing. The male sterility was caused by the conversion of
      tetradynamous stamens into carpelloid structures with stigmatoid tissues at their
      tips and ovule-like tissues in the margins, and the two shorter stamens into
      filaments without anthers. The feminized development of the stamens resulted in
      the complete lack of pollen grains, which was stable in different years and
      environments. The pistils of inap CMS displayed normal morphology and good seed
      set after pollinated by B. napus. Histological sections showed that the
      developmental alteration of the stamens initiated at the stage of stamen
      primordium differentiation. AFLP analysis of the nuclear genomic composition with
      23 pairs of selective primers detected no woad DNA bands in inap CMS. Twenty out
      of 25 mitochondrial genes originated from I. indigotica, except for cox2-2 which
      was the recombinant between cox2 from woad and cox2-2 from rapeseed. The novel
      cox2-2 was transcribed in flower buds of inap CMS weakly and comparatively with
      the fertile B. napus addition line Me harboring one particular woad chromosome.
      The restorers of other autoplasmic and alloplasmic CMS systems in rapeseed failed
      to restore the fertility of inap CMS and the screening of B. napus wide resources
      found no fertility restoration variety, showing its distinct origin and the
      related mechanism of sterility. The reasons for the mitochondrial rearrangements
      and the breeding of the restorer for the novel CMS system were discussed.

PMID- 28428800
TI  - Effect of Enamel Caries Lesion Baseline Severity on Fluoride Dose-Response.
AB  - This study aimed to investigate the effect of enamel caries lesion baseline
      severity on fluoride dose-response under pH cycling conditions. Early caries
      lesions were created in human enamel specimens at four different severities (8,
      16, 24, and 36 h). Lesions were allocated to treatment groups (0, 83, and 367 ppm
      fluoride as sodium fluoride) based on Vickers surface microhardness (VHN) and pH
      cycled for 5 d. The cycling model comprised 3 * 1 min fluoride treatments
      sandwiched between 2 * 60 min demineralization challenges with specimens stored
      in artificial saliva in between. VHN was measured again and changes versus lesion
      baseline were calculated (DeltaVHN). Data were analyzed using two-way ANOVA (p <
      0.05). Increased demineralization times led to increased surface softening. The
      lesion severity*fluoride concentration interaction was significant (p < 0.001).
      Fluoride dose-response was observed in all groups. Lesions initially
      demineralized for 16 and 8 h showed similar overall rehardening (DeltaVHN) and
      more than 24 and 36 h lesions, which were similar. The 8 h lesions showed the
      greatest fluoride response differential (367 versus 0 ppm F) which diminished
      with increasing lesion baseline severity. The extent of rehardening as a result
      of the 0 ppm F treatment increased with increasing lesion baseline severity,
      whereas it decreased for the fluoride treatments. In conclusion, lesion baseline
      severity impacts the extent of the fluoride dose-response.

PMID- 28428801
TI  - Preconception allergen sensitization can induce B10 cells in offspring: a
      potential main role for maternal IgG.
AB  - BACKGROUND: The mechanisms through which allergies can be inhibited after
      preconception immunization with allergens are not fully understood. We aimed to
      evaluate whether maternal immunization can induce a regulatory B (B10) cell
      population in offspring in concert with allergy inhibition. METHODS: C57BL/6
      females were or were not immunized with OVA and were mated with normal WT males.
      Their offspring were evaluated at 3 days of age or 20 days after neonatal
      immunization. Human peripheral B cells from atopic and non-atopic individuals
      were also evaluated. RESULTS: Preconception OVA immunization induced B10 cells in
      offspring, and IL-10 production appeared to be critical for FcgammaRIIB
      upregulation in offspring B cells. Murine and human IL-10-producing B cells
      responded in vitro to IgG according to the atopic repertoire of the cells.
      CONCLUSIONS: Our results reveal that maternal immunization induces allergen
      specific B10 cells in offspring and a pivotal role for the IgG repertoire in IL
      10 production by murine and human B cells.

PMID- 28428802
TI  - Regulation of Th2 responses by different cell types expressing the interleukin-31
      receptor.
AB  - BACKGROUND: Interleukin-31 (IL-31) is a recently identified cytokine produced by
      Th2 cells that is involved in the development of atopic dermatitis-induced skin
      inflammation and pruritus. Its receptor, IL-31RA, is expressed by a number of
      cell types, including epithelial cells, eosinophils, and activated monocytes and
      macrophages. To date, however, the regulation of Th2 responses by distinct cell
      types and tissues expressing IL-31RA has not been well studied. METHODS: In this
      study, Cry j 2, one of the major allergens of Japanese cedar pollen, was
      administered to IL-31RA-deficient or wild-type (WT) mice via nasal or
      intraperitoneal injection for induction of specific Th2 responses. RESULTS: After
      nasal administration of Cry j 2, IL-31RA-deficient mice showed lower Cry j 2
      specific CD4+ T cell proliferation, Th2 cytokine (IL-5 and IL-13) production, and
      Th2-mediated (IgE, IgG1, and IgG2b) antibody responses than WT mice. In contrast,
      IL-31RA-deficient mice administered Cry j 2 intraperitoneally showed stronger Th2
      immune responses than WT mice. CONCLUSIONS: These results indicate that IL-31R
      signaling positively regulates Th2 responses induced by nasal administration of
      Cry j 2, but negatively regulates these responses when Cry j 2 is administered
      intraperitoneally. Collectively, these data indicate that the induction of
      antigen-specific Th2 immune responses might depend on tissue-specific cell types
      expressing IL-31RA.

PMID- 28428803
TI  - Distribution of Mast Cells and Locations, Depths, and Sizes of the Putative
      Acupoints CV 8 and KI 16.
AB  - The anatomical locations and sizes of acupuncture points (APs) are identified in
      traditional Chinese medicine by using the cun measurement method. More precise
      knowledge of those locations and sizes to submillimeter precision, along with
      their cytological characterizations, would provide significant contributions both
      to scientific investigations and to precise control of the practice of
      acupuncture. Over recent decades, researchers have come to realize that APs in
      the skin of rats and humans have more mast cells (MCs) than neighboring
      nonacupoints. In this work, the distribution of MCs in the ventral skin of mice
      was studied so that it could be used to infer the locations, depths from the
      epidermis, and sizes of three putative APs. The umbilicus was taken as the
      reference point, and a transversal cross section through it was studied. The
      harvested skins from 8-week-old mice were stained with toluidine blue, and the
      MCs were recognized by their red-purple stains and their metachromatic granules.
      The three putative APs, CV 8 and the left and the right KI 16 APs, were
      identified based on their high densities of MCs. These findings also imply that
      acupuncture may stimulate, through MCs, an immune response to allergic
      inflammation.

PMID- 28428804
TI  - Morphogenesis of honeybee hypopharyngeal gland during pupal development.
AB  - BACKGROUND: The hypopharyngeal gland of worker bees contributes to the production
      of the royal jelly fed to queens and larvae. The gland consists of thousands of
      two-cell units that are composed of a secretory cell and a duct cell and that are
      arranged in sets of about 12 around a long collecting duct. RESULTS: By
      fluorescent staining, we have examined the morphogenesis of the hypopharyngeal
      gland during pupal life, from a saccule lined by a pseudostratified epithelium to
      the elaborate organ of adult worker bees. The hypopharyngeal gland develops as
      follows. (1) Cell proliferation occurs during the first day of pupal life in the
      hypopharyngeal gland primordium. (2) Subsequently, the epithelium becomes
      organized into rosette-like units of three cells. Two of these will become the
      secretory cell and the duct cell of the adult secretory units; the third cell
      contributes only temporarily to the development of the secretory units and is
      eliminated by apoptosis in the second half of pupal life. (3) The three-cell
      units of flask-shaped cells undergo complex changes in cell morphology. Thus, by
      mid-pupal stage, the gland is structurally similar to the adult hypopharyngeal
      gland. (4) Concomitantly, the prospective secretory cell attains its
      characteristic subcellular organization by the invagination of a small patch of
      apical membrane domain, its extension to a tube of about 100 MUm in length
      (termed a canaliculus), and the expansion of the tube to a diameter of about 3
      MUm. (6) Finally, the canaliculus-associated F-actin system becomes reorganized
      into rings of bundled actin filaments that are positioned at regular distances
      along the membrane tube. CONCLUSIONS: The morphogenesis of the secretory units in
      the hypopharyngeal gland of the worker bee seems to be based on a developmental
      program that is conserved, with slight modification, among insects for the
      production of dermal glands. Elaboration of the secretory cell as a unicellular
      seamless epithelial tube occurs by invagination of the apical membrane, its
      extension likely by targeted exocytosis and its expansion, and finally the
      reorganisation of the membrane-associated F-actin system. Our work is fundamental
      for future studies of environmental effects on hypopharyngeal gland morphology
      and development.

PMID- 28428805
TI  - Edible dormice (Glis glis) avoid areas with a high density of their preferred
      food plant - the European beech.
AB  - BACKGROUND: Numerous species, especially among rodents, are strongly affected by
      the availability of pulsed resources. The intermittent production of large seed
      crops in northern hemisphere tree species (e.g., beech Fagus spec.,oak Quercus
      spec., pine trees Pinus spec.) are prime examples of these resource pulses. Adult
      edible dormice are highly dependent on high energy seeds to maximize their
      reproductive output. For juvenile dormice the energy rich food is important to
      grow and fatten in a very short time period prior to hibernation. While these
      erratic, often large-scale synchronized mast events provide overabundant seed
      availability, a total lack of seed production can be observed in so-called mast
      failure years. We hypothesized that dormice either switch territories between
      mast and non-mast years, to maximize energy availability or select habitats in
      which alternative food sources are also available (e.g., fleshy fruits, cones).
      To analyze the habitat preferences of edible dormice we performed environmental
      niche factor analyses (ENFA) for 9 years of capture-recapture data. RESULTS: As
      expected, the animals mainly used areas with high canopy closure and vertical
      stratification, probably to avoid predation. Surprisingly, we found that dormice
      avoided areas with high beech tree density, but in contrast preferred areas with
      a relatively high proportion of coniferous trees. Conifer cones and leaves can be
      an alternative food source for edible dormice and are less variable in
      availability. CONCLUSION: Therefore, we conclude that edible dormice try to avoid
      areas with large fluctuations in food availability to be able to survive years
      without mast in their territory.

PMID- 28428806
TI  - Is low total cholesterol levels associated with suicide attempt in depressive
      patients?
AB  - BACKGROUND: Patients with major depressive disorder (MDD) have a high risk of
      suicide. Many pathophysiological factors involved in MDD and suicide such us a
      low cholesterol levels have been associated with MDD and increased vulnerability
      to suicide. In this study, we investigate the relation between lipid parameters
      and suicide risk in patients with MDD. METHODS: Plasma levels of total
      cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and
      low-density lipoprotein cholesterol (LDL-c) were determined in 160 patients
      meeting the DSM-IV-TR criteria for MDD (110 patients without suicidal behavior
      and 52 suicidal attempters) and 151 healthy controls. RESULTS: A significant
      decrease in plasma cholesterol levels was observed in the group of suicidal
      depressive patients compared to those without suicidal behavior (p < 0.001). For
      the other lipid levels (triglycerides, HDL cholesterol, and LDL cholesterol),
      there were no significant differences between suicidal and non-suicidal patients.
      CONCLUSIONS: Our study showed a significant decrease in plasma cholesterol levels
      in suicidal patients. This result support the hypothesis of the association of
      low plasma cholesterol level and suicidal behavior in patients with major
      depressive disorder.

PMID- 28428807
TI  - Effect of breastfeeding versus infant formula on iron status of infants with beta
      thalassemia major.
AB  - BACKGROUND: Thalassemia major or Cooley's anemia is the most severe form of beta
      thalassemia in which the complete lack of beta protein in the hemoglobin causes a
      life-threatening anemia requiring regular blood transfusions and extensive
      ongoing medical care. These extensive, lifelong blood transfusions lead to iron
      overload that must be treated with chelation therapy to prevent early death from
      organ failure. We compared serum iron and ferritin levels amongst infants aged up
      to one year with beta thalassemia major according to their feeding types,
      including exclusively breastfed, exclusively formula fed and combined (both
      breast and formula) fed types. METHODS: Sixty out of 176 screened infants with
      transfusion dependant beta thalassemia major were recruited from the outpatient
      clinic of thalassemia at Zagazig University Hospital in Egypt, between 2007 and
      2014. Patients were classified into three groups (20 patients per group)
      according to type of feeding. Group 1: exclusive breastfeeding, around 6-8 feeds
      per day; group 2: exclusive infant formula feeding, 120-150 ml of formula per
      kilogram of body weight per day divided into 6-8 feeds and group 3: combined
      breastfeeding and formula per day. RESULTS: Serum iron and ferritin levels were
      lower in group 1 compared to groups 2 and 3. The mean serum iron for group 1 was
      73, 87 and 96 ug/dl at 6, 9 and 12 months respectively, while that for group 2
      was 85, 99 and 112 ug/dl at 6, 9 and 12 months respectively and for group 3 was
      78, 92 and 99 ug/dl at 6, 9 and 12 months respectively. The mean serum ferritin
      for group 1 was 283, 327 and 497 ng/ml at 6, 9 and 12 months respectively, while
      that for group 2 was 310, 389 and 591 ng/ml at 6, 9 and 12 months respectively
      and for group 3 was 291, 345 and 515 ng/ml at 6, 9 and 12 months respectively.
      The differences were not statistically significant. CONCLUSIONS: Breastfed
      infants with beta thalassemia major may accumulate less iron than infants fed
      iron fortified formula anticipating later onset of iron overload in the breastfed
      infants. Larger studies are needed to support these findings.

PMID- 28428808
TI  - Reference genes for normalization of qPCR assays in sugarcane plants under water
      deficit.
AB  - BACKGROUND: Sugarcane (Saccharum spp.) is the main raw material for sugar and
      ethanol production. Among the abiotic stress, drought is the main one that
      negatively impact sugarcane yield. Although gene expression analysis through
      quantitative PCR (qPCR) has increased our knowledge about biological processes
      related to drought, gene network that mediates sugarcane responses to water
      deficit remains elusive. In such scenario, validation of reference gene is a
      major requirement for successful analyzes involving qPCR. RESULTS: In this study,
      candidate genes were tested for their suitable as reference genes for qPCR
      analyses in two sugarcane cultivars with varying drought tolerance. Eight
      candidate reference genes were evaluated in leaves sampled in plants subjected to
      water deficit in both field and greenhouse conditions. In addition, five genes
      were evaluated in shoot roots of plants subjected to water deficit by adding
      PEG8000 to the nutrient solution. NormFinder and RefFinder algorithms were used
      to identify the most stable gene(s) among genotypes and under different
      experimental conditions. Both algorithms revealed that in leaf samples, UBQ1 and
      GAPDH genes were more suitable as reference genes, whereas GAPDH was the best
      reference one in shoot roots. CONCLUSION: Reference genes suitable for sugarcane
      under water deficit were identified, which would lead to a more accurate and
      reliable analysis of qPCR. Thus, results obtained in this study may guide future
      research on gene expression in sugarcane under varying water conditions.

PMID- 28428809
TI  - Leucine-rich-repeat-containing variable lymphocyte receptors as modules to target
      plant-expressed proteins.
AB  - BACKGROUND: The ability to target and manipulate protein-based cellular processes
      would accelerate plant research; yet, the technology to specifically and
      selectively target plant-expressed proteins is still in its infancy. Leucine-rich
      repeats (LRRs) are ubiquitously present protein domains involved in mediating
      protein-protein interactions. LRRs confer the binding specificity to the highly
      diverse variable lymphocyte receptor (VLR) antibodies (including VLRA, VLRB and
      VLRC types) that jawless vertebrates make as the functional equivalents of jawed
      vertebrate immunoglobulin-based antibodies. RESULTS: In this study, VLRBs
      targeting an effector protein from a plant pathogen, HopM1, were developed by
      immunizing lampreys and using yeast surface display to select for high-affinity
      VLRBs. HopM1-specific VLRBs (VLRM1) were expressed in planta in the cytosol, the
      trans-Golgi network, and the apoplast. Expression of VLRM1 was higher when the
      protein localized to an oxidizing environment that would favor disulfide bridge
      formation (when VLRM1 was not localized to the cytoplasm), as disulfide bonds are
      necessary for proper VLR folding. VLRM1 specifically interacted in planta with
      HopM1 but not with an unrelated bacterial effector protein while HopM1 failed to
      interact with a non-specific VLRB. CONCLUSIONS: In the future, VLRs may be used
      as flexible modules to bind proteins or carbohydrates of interest in planta, with
      broad possibilities for their use by binding directly to their targets and
      inhibiting their action, or by creating chimeric proteins with new specificities
      in which endogenous LRR domains are replaced by those present in VLRs.

PMID- 28428810
TI  - Recent achievements obtained by chloroplast transformation.
AB  - Chloroplasts play a great role for sustained wellbeing of life on the planet.
      They have the power and raw materials that can be used as sophisticated
      biological factories. They are rich in energy as they have lots of pigment
      protein complexes capable of collecting sunlight, in sugar produced by
      photosynthesis and in minerals imported from the plant cell. Chloroplast genome
      transformation offers multiple advantages over nuclear genome which among others,
      include: integration of the transgene via homologus recombination that enables to
      eliminate gene silencing and position effect, higher level of transgene
      expression resulting into higher accumulations of foreign proteins, and
      significant reduction in environmental dispersion of the transgene due to
      maternal inheritance which helps to minimize the major critic of plant genetic
      engineering. Chloroplast genetic engineering has made fruit full progresses in
      the development of plants resistance to various stresses, phytoremediation of
      toxic metals, and production of vaccine antigens, biopharmaceuticals, biofuels,
      biomaterials and industrial enzymes. Although successful results have been
      achieved, there are still difficulties impeding full potential exploitation and
      expansion of chloroplast transformation technology to economical plants. These
      include, lack of species specific regulatory sequences, problem of selection and
      shoot regeneration, and massive expression of foreign genes resulting in
      phenotypic alterations of transplastomic plants. The aim of this review is to
      critically recapitulate the latest development of chloroplast transformation with
      special focus on the different traits of economic interest.

PMID- 28428811
TI  - Role of intraoperative cholangiography for detecting residual stones after
      biliary pancreatitis: still useful? A retrospective study.
AB  - BACKGROUND: Intraoperative cholangiography (IOC) may detect residual stones in
      the common bile duct (CBD) after acute biliary pancreatitis (ABP). The aim of the
      present study is to analyze the utility of IOC in detecting residual stones in
      patients undergoing cholecystectomy for ABP and if complications are related with
      this procedure. METHODS: Demographic and clinical factors were assessed in
      patients with mild ABP who underwent IOC during laparoscopic cholecystectomy.
      Factors assessed included preoperative size of the CBD on ultrasonography,
      presence of stones in the gallbladder and the CBD, and IOC results. For the
      statistical analysis, chi2 or Fisher's exact tests to compare proportions and the
      nonparametric Mann-Whitney U test for analysis of values with abnormal
      distribution were used. RESULTS: The study included 113 patients, 82 males
      (72.6%) and 31 females (27.4%), of mean age 46.9 +/- 14.7 years (range 18-86
      years). All preoperative laboratory indicators were elevated. The group of the
      patients with stones in the CBD diagnosed by IOC was divided in patients with
      diameters <0.8 mm and with diameters >=0.8 mm of the CBD diagnosed preoperatively
      with ultrasound. The laboratory tests do not demonstrate difference statistically
      significative between these two groups. The group of the patients without stones
      in the CBD diagnosed by IOC was also divided in patients with diameters <0.8 mm
      and with diameters >=0.8 mm of the CBD. Also in these two groups, the statistical
      analysis of the laboratory tests does not demonstrate significative difference.
      Most procedures were performed by specialists (64.6%), and all patients underwent
      IOC. IOC showed stones in 84/113 patients (74.3%). A comparison of patients with
      and without stones at IOC showed similar mean times from hospitalization to
      surgery (5.9 days [range 2-12 days] vs. 6.1 days [range 2-23 days]), from surgery
      until hospital discharge (2.0 days [range 0-4 days] vs. 2.2 days [range 0-11
      days]), and overall length of stay (7.9 days [range 3-19 days] vs. 8.3 days
      [range 3-23 days]) (P > 0.001). CONCLUSIONS: IOC is useful to diagnose residual
      CBD stones, without increasing complications related to the procedure itself.

PMID- 28428812
TI  - Treatment for female patients with eating disorders in the largest medical prison
      in Japan.
AB  - The number of offenders with eating disorders in women's prisons in Japan has
      grown annually over the last 15 years. Women's prisons have experienced
      significant difficulties in the management of patients with eating disorders who
      have body-critical complications arising from low body weight, in addition to
      behavioral problems. Patients in Japan's 185 correctional facilities who display
      high refractoriness or who present a physical risk are transferred to the
      Hachioji medical prison, a national specialty hospital operated by the Ministry
      of Justice. The medical prison must manage any psychosomatic problems necessary
      for the safety of inmates regardless of a patient's wishes. The most common
      conviction resulting in imprisonment of women with eating disorders was
      shoplifting (n = 44; 63%), with the second most common being drug-offenses (n =
      17; 24%). While shoplifting is of concern in relation to eating disorders, a
      causal relationship remains unclear. Most patients in the shoplifting group did
      not have histories of antisocial and/or impulsive behaviors such as drug abuse,
      sexual deviation, self-injury, or other criminal activity. Instead, shoplifting
      appears to be an obsessive-compulsive behavior deeply rooted in the
      psychopathology of severe eating disorder patients. Patients in this group tended
      to have histories of relatively high education and steady employment, although
      most also had histories of prolonged eating disorders and unstable treatment.
      Although adherence to treatment was poor among patients with eating disorders in
      the medical prison, body weight and behavioral problems improved following
      treatment in the special compulsory environment, without severe sequelae or
      patient death. The Ministry of Justice recently established another specialized
      ward for the care for female patients with eating disorders. If greater emphasis
      is placed on early-stage, protective, medical treatment, the number of patients
      with eating disorders in prisons may decrease. Further research is required to
      investigate the relationship between shoplifting and eating disorders.

PMID- 28428813
TI  - Perinatal depression in Nigeria: perspectives of women, family caregivers and
      health care providers.
AB  - BACKGROUND: Perinatal maternal depression is common and undertreated in many sub
      Saharan African countries, including Nigeria. While culture shapes the social
      determinants and expression of depressive symptoms, there is a dearth of research
      investigating these processes in African contexts. METHODS: To address this gap,
      we conducted in-depth interviews with 14 women with perinatal depression, 14 of
      their family caregivers and 11 health providers, using the McGill Illness
      Narrative Interview as part of a larger trial of a stepped-care intervention.
      Interpretation of themes was guided by cultural constructivist and critical
      anthropological perspectives that situate perinatal depression in its complexity
      as a disorder that is embedded in webs of social relations and embodied
      practices. RESULTS: Study respondents used idioms of distress that identified
      perinatal conditions that consist of somatic, affective, cognitive and behavior
      symptoms found in depressive disorders. Respondents viewed mental health problems
      in the perinatal period as tied to sociomoral concerns over gender roles and
      women's position within the household. Conflict between women's effort to be
      assertive to address interpersonal problems, while needing to be seen as non
      aggressive contributed to their distress. Causal explanations for depression
      included husband's lack of care, family problems, "spiritual attack", having a
      female child when a male child was desired, and not resting sufficiently after
      childbirth. Guilt about breaching social norms for women's conduct contributed to
      self blame, and feelings of shame. CONCLUSIONS: Clinical assessment and
      interventions as well as public health prevention strategies for perinatal
      depression in global mental health need to consider local social contexts and
      meanings of depression, which can be explored with narrative-based methods.

PMID- 28428814
TI  - Reliability and validity of the Japanese version of the Community Integration
      Measure for community-dwelling people with schizophrenia.
AB  - BACKGROUND: Community integration is an essential right for people with
      schizophrenia that affects their well-being and quality of life, but no valid
      instrument exists to measure it in Japan. The aim of the present study is to
      develop and evaluate the reliability and validity of the Japanese version of the
      Community Integration Measure (CIM) for people with schizophrenia. METHODS: The
      Japanese version of the CIM was developed as a self-administered questionnaire
      based on the original version of the CIM, which was developed by McColl et al.
      This study of the Japanese CIM had a cross-sectional design. Construct validity
      was determined using a confirmatory factor analysis (CFA) and data from 291
      community-dwelling people with schizophrenia in Japan. Internal consistency was
      calculated using Cronbach's alpha. The Lubben Social Network Scale (LSNS-6), the
      Rosenberg Self-Esteem Scale (RSE) and the UCLA Loneliness Scale, version 3
      (UCLALS) were administered to assess the criterion-related validity of the
      Japanese version of the CIM. RESULTS: The participants were 263 people with
      schizophrenia who provided valid responses. The Cronbach's alpha was 0.87, and
      CFA identified one domain with ten items that demonstrated the following values:
      goodness of fit index = 0.924, adjusted goodness of fit index = 0.881,
      comparative fit index = 0.925, and root mean square error of approximation =
      0.085. The correlation coefficients were 0.43 (p < 0.001) with the LSNS-6, 0.42
      (p < 0.001) with the RSE, and -0.57 (p < 0.001) with the UCLALS. CONCLUSIONS: The
      Japanese version of the CIM demonstrated adequate reliability and validity for
      assessing community integration for people with schizophrenia in Japan.

PMID- 28428815
TI  - Service user and care giver involvement in mental health system strengthening in
      Nepal: a qualitative study on barriers and facilitating factors.
AB  - BACKGROUND: Service user and caregiver involvement has become an increasingly
      common strategy to enhance mental health outcomes, and has been incorporated in
      the mental healthpolicies of many developed nations. However, this practice is
      non-existent or fragmented in low and middle income countries (LMICs). Instances
      of service user and caregiver involvement have been rising slowly in a few LMICs,
      but are rarely described in the literature. Very little is known about the
      context of user and caregiver participation in mental health system strengthening
      processes in a low-income, disaster- and conflict-affected state such as Nepal.
      METHODS: This study explores (a) the extent and experiences of service user and
      caregiver involvement in policy making, service planning, monitoring, and
      research in Nepal; (b) perceived barriers to such involvement; and (c) possible
      strategies to overcome barriers. Key Informant Interviews (n = 24) were conducted
      with service users and caregivers who were either affiliated to a mental health
      organization or receiving menta health care integrated within primary care.
      Purposive sampling was employed. Data collection was carried out in 2014 in
      Chitwan and Kathmandu districts of Nepal. Data analysis was carried out in
      NVivo10 using a framework approach. RESULTS: The involvement of service users
      affiliated to mental health organizations in policy development was reported to
      be 'tokenistic'. Involvement of caregivers was non-existent. Perceived barriers
      to greater involvement included lack of awareness, stigma and discrimination,
      poor economic conditions, the centralized health system, and lack of strong
      leadership and unity among user organizations. Increased focus on reducing public
      as well as self-stigma, improved policy frameworks and initiatives, and
      decentralization of care are some strategies that may facilitate service user and
      caregiver involvement. CONCLUSION: The study highlighted need for user and
      caregiver networks free from competing interests and priorities. Improved policy
      frameworks and decentralization of care may support meaningful service user and
      caregiver involvement.

PMID- 28428816
TI  - Physical health policies and metabolic screening in mental health care systems of
      sub-Saharan African countries: a systematic review.
AB  - BACKGROUND: There is a need for interventions to address the escalating mental
      health burden in sub-Saharan Africa (SSA). Addressing physical health needs
      should have a central role in reducing the burden and facilitating recovery in
      people with severe mental illness (SMI). We systematically investigated (1)
      physical health policies in the current mental health plans, and (2) the routine
      metabolic screening rates for people with SMI in SSA. METHODS: The Mental Health
      Atlas and MiNDbank of the World Health Organization were screened for physical
      health policies in mental health plans. Next, we systematically searched PubMed
      from inception until February 1st, 2017 for relevant studies on metabolic
      screening rates in people with SMI in SSA. RESULTS: The current systematic review
      shows that in 22 screened plans only 6 made reference to a physical health
      component or policy. Only the South-African mental health plan reported about
      routine screening and treatment of physical illness for people with SMI. In 2
      South-African studies (n = 431) routine screening was unacceptably low with less
      than 1% adequately screened for all modifiable metabolic syndrome risk factors.
      CONCLUSIONS: Our review data clearly show that a physical health policy is yet to
      be embraced in mental health care systems of most SSA countries. There is a clear
      need for integrated mental and medical services in SSA. All psychiatric services,
      including poorly developed community-based primary health care settings should
      standardly assess the body mass index and waist circumference at initiation of
      psycho-pharmacotherapy, and afterwards at regular intervals. Optimal monitoring
      should include assessments of fasting glucose, lipids, cholesterol, and blood
      pressure. Mental health care providers in SSA countries need to be informed that
      their roles extend beyond taking care of the mental health of their patients and
      assume responsibility for the physical health of their patients as well. Policy
      makers should be made aware that investment in continued medial education and in
      screening for physical health risks could optimize mental and physical health
      improvements. The increased physical health needs of people with mental illness
      should be integrated into the existing Information, Education and Communication
      public health awareness programs of the World Health Organization.

PMID- 28428817
TI  - Prevalence and correlates of ADHD among adolescents in a Beirut community sample:
      results from the BEI-PSY Study.
AB  - BACKGROUND: This study aims to investigate the prevalence, correlates and
      treatment seeking behavior related to ADHD among adolescents from Lebanon.
      METHODS: Five hundred and ten adolescents were recruited through multistage
      stratified cluster sampling of households in Beirut, and separately interviewed
      along with one parent/legal guardian, using the DAWBA. All adolescents completed
      the PRQ and the SDQ; the parent/legal guardian also completed the SDQ and
      provided basic demographic information, including attitudes towards seeking
      mental health services. RESULTS: 10.20% of the adolescents were diagnosed with
      ADHD. Having ADHD was associated with having academic difficulties and being
      involved in bullying. Adolescents with ADHD also had higher odds of drinking
      alcohol, smoking cigarettes, and having comorbid emotional and conduct disorders
      (compared to those without ADHD). Adolescents with ADHD and their parents
      reported a higher burden of illness and were more likely to consider seeing a
      mental health professional than healthy adolescents and their parents.
      CONCLUSION: ADHD among adolescents in Lebanon warrants closer attention, mainly
      increased awareness in the larger public, and stronger commitment to increase
      treatment resources to the community.

PMID- 28428818
TI  - Does parent-child agreement vary based on presenting problems? Results from a UK
      clinical sample.
AB  - BACKGROUND: Discrepancies are often found between child and parent reports of
      child psychopathology, nevertheless the role of the child's presenting
      difficulties in relation to these is underexplored. This study investigates
      whether parent-child agreement on the conduct and emotional scales of the
      Strengths and Difficulties Questionnaire (SDQ) varied as a result of certain
      child characteristics, including the child's presenting problems to clinical
      services, age and gender. METHODS: The UK-based sample consisted of 16,754
      clinical records of children aged 11-17, the majority of which were female (57%)
      and White (76%). The dataset was provided by the Child Outcomes Research
      Consortium , which collects outcome measures from child services across the UK.
      Clinicians reported the child's presenting difficulties, and parents and children
      completed the SDQ. RESULTS: Using correlation analysis, the main findings
      indicated that agreement varied as a result of the child's difficulties for
      reports of conduct problems, and this seemed to be related to the presence or
      absence of externalising difficulties in the child's presentation. This was not
      the case for reports of emotional difficulties. In addition, agreement was higher
      when reporting problems not consistent with the child's presentation; for
      instance, agreement on conduct problems was greater for children presenting with
      internalising problems. Lastly, the children's age and gender did not seem to
      have an impact on agreement. CONCLUSIONS: These findings demonstrate that certain
      child presenting difficulties, and in particular conduct problems, may be related
      to informant agreement and need to be considered in clinical practice and
      research. Trial Registration This study was observational and as such did not
      require trial registration.

PMID- 28428819
TI  - Lipid production and molecular dynamics simulation for regulation of accD gene in
      cyanobacteria under different N and P regimes.
AB  - BACKGROUND: Microalgae grown under different nutrient deficient conditions
      present a good source of natural lipids with applications for several types of
      biofuels. The expression of acetyl-CoA carboxylase gene can further provide an
      insight to the mechanisms leading to enhanced lipid production under such
      stresses. In this study, two nutrients viz. nitrogen and phosphorus were
      modulated to see its effect on lipid productivity in selected cyanobacteria and
      its correlation with Accase followed by molecular dynamics simulation. RESULTS:
      Selected cyanobacteria viz. Oscillatoria sp. (SP8), Anabaena sp. (SP12), Anabaena
      sp. (SP13), Microcoleus sp. (SP18), and Nostoc sp. (SP20) varied in their ability
      to accumulate lipids which ranged from a lowest of 0.13% in Anabaena sp. (SP13)
      to the maximum of 7.24% in Microcoleus sp. (SP18). Microcoleus sp. (SP18) also
      recorded highest lipid accumulation at both N (6 mM NaNO3) and P (0.20 mM K2HPO4)
      limiting conditions. The overall expression of accD was found to be upregulated
      in both Oscillatoria sp. (SP8) and Microcoleus sp. (SP18) for all nitrogen
      concentrations but was differentially regulated with both positive and negative
      induction under phosphorus stress conditions. Maximum induction was observed in
      Microcoleus sp. (SP18) at 0.20 mM K2HPO4. The obtained 3D structure of SP8
      protein (21.8 kDa) showed six alpha helices, while SP18 protein (16.7 kDa)
      exhibited four alpha helices and four beta sheets. The phi (phi)/psi(psi) angles
      of the amino acid residues observed in Ramachandran plot analysis showed that
      both SP8 and SP18 proteins were highly stable with more than 90% amino acids in
      allowed regions. The molecular dynamics simulation results also indicated the
      stability of ligand-bound protein complexes. CONCLUSION: It has been demonstrated
      that cyanobacterial isolates are affected differently by nutrient limitation
      leading to variation in their lipid productivity. The same has been revealed by
      the behavior of accD gene expression which was regulated more by nutrients
      concentrations rather than the organism. However, the ligand-bound protein
      complexes were stable throughout MD simulations.

PMID- 28428820
TI  - Regional water footprints of potential biofuel production in China.
AB  - BACKGROUND: Development of biofuels is considered as one of the important ways to
      replace conventional fossil energy and mitigate climate change. However, rapid
      increase of biofuel production could cause other environmental concerns in China
      such as water stress. This study is intended to evaluate the life-cycle water
      footprints (WF) of biofuels derived from several potential non-edible feedstocks
      including cassava, sweet sorghum, and Jatropha curcas in China. Different water
      footprint types including blue water, green water, and grey water are considered
      in this study. Based on the estimated WF, water deprivation impact and water
      stress degree on local water environment are further analyzed for different
      regions in China. RESULTS: On the basis of the feedstock resource availability,
      sweet sorghum, cassava, and Jatropha curcas seeds are considered as the likely
      feedstocks for biofuel production in China. The water footprint results show that
      the feedstock growth is the most water footprint intensive process, while the
      biofuel conversion and transportation contribute little to total water
      footprints. Water footprints vary significantly by region with climate and soil
      variations. The life-cycle water footprints of cassava ethanol, sweet sorghum
      ethanol, and Jatropha curcas seeds biodiesel were estimated to be 73.9-222.2,
      115.9-210.4, and 64.7-182.3 L of water per MJ of biofuel, respectively. Grey
      water footprint dominates the life-cycle water footprint for each type of the
      biofuels. Development of biofuels without careful water resource management will
      exert significant impacts on local water resources. The water resource impacts
      vary significantly among regions. For example, based on blue and grey water
      consumption, Gansu province in China will suffer much higher water stress than
      other regions do due to limited available water resources and large amount of
      fertilizer use in that province. In term of blue water, Shandong province is
      shown with the most severe water stress issue, followed by Gansu province, which
      is attributed to the limited water resources in both provinces. CONCLUSIONS: By
      considering feedstock resource distribution, biofuel production potentials, and
      estimated water footprints, this study provides insight into the impact of
      biofuel production on the local water environment in China. Biofuel development
      policies need to be carefully designed for the sustainable development of
      biofuels in China.

PMID- 28428821
TI  - Genome-wide search for candidate genes for yeast robustness improvement against
      formic acid reveals novel susceptibility (Trk1 and positive regulators) and
      resistance (Haa1-regulon) determinants.
AB  - BACKGROUND: Formic acid is an inhibitory compound present in lignocellulosic
      hydrolysates. Understanding the complex molecular mechanisms underlying
      Saccharomyces cerevisiae tolerance to this weak acid at the system level is
      instrumental to guide synthetic pathway engineering for robustness improvement of
      industrial strains envisaging their use in lignocellulosic biorefineries.
      RESULTS: This study was performed to identify, at a genome-wide scale, genes
      whose expression confers protection or susceptibility to formic acid, based on
      the screening of a haploid deletion mutant collection to search for these
      phenotypes in the presence of 60, 70 and 80 mM of this acid, at pH 4.5. This
      chemogenomic analysis allowed the identification of 172 determinants of tolerance
      and 41 determinants of susceptibility to formic acid. Clustering of genes
      required for maximal tolerance to this weak acid, based on their biological
      function, indicates an enrichment of those involved in intracellular trafficking
      and protein synthesis, cell wall and cytoskeleton organization, carbohydrate
      metabolism, lipid, amino acid and vitamin metabolism, response to stress,
      chromatin remodelling, transcription and internal pH homeostasis. Among these
      genes is HAA1 encoding the main transcriptional regulator of yeast transcriptome
      reprograming in response to acetic acid and genes of the Haa1-regulon; all
      demonstrated determinants of acetic acid tolerance. Among the genes that when
      deleted lead to increased tolerance to formic acid, TRK1, encoding the high
      affinity potassium transporter and a determinant of resistance to acetic acid,
      was surprisingly found. Consistently, genes encoding positive regulators of Trk1
      activity were also identified as formic acid susceptibility determinants, while a
      negative regulator confers protection. At a saturating K+ concentration of 20 mM,
      the deletion mutant trk1Delta was found to exhibit a much higher tolerance
      compared with the parental strain. Given that trk1Delta accumulates lower levels
      of radiolabelled formic acid, compared to the parental strain, it is hypothesized
      that Trk1 facilitates formic acid uptake into the yeast cell. CONCLUSIONS: The
      list of genes resulting from this study shows a few marked differences from the
      list of genes conferring protection to acetic acid and provides potentially
      valuable information to guide improvement programmes for the development of more
      robust strains against formic acid.

PMID- 28428822
TI  - In muro deacetylation of xylan affects lignin properties and improves
      saccharification of aspen wood.
AB  - BACKGROUND: Lignocellulose from fast growing hardwood species is a preferred
      source of polysaccharides for advanced biofuels and "green" chemicals. However,
      the extensive acetylation of hardwood xylan hinders lignocellulose
      saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory
      acetic acid concentrations during microbial sugar fermentation. To optimize
      lignocellulose for cost-effective saccharification and biofuel production, an
      acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and
      targeted to cell walls. RESULTS: AnAXE1-expressing plants exhibited reduced xylan
      acetylation and grew normally. Without pretreatment, their lignocellulose yielded
      over 25% more glucose per unit mass of wood (dry weight) than wild-type plants.
      Glucose yields were less improved (+7%) after acid pretreatment, which hydrolyses
      xylan. The results indicate that AnAXE1 expression also reduced the molecular
      weight of xylan, and xylan-lignin complexes and/or lignin co-extracted with
      xylan, increased cellulose crystallinity, altered the lignin composition,
      reducing its syringyl to guaiacyl ratio, and increased lignin solubility in
      dioxane and hot water. Lignin-associated carbohydrates became enriched in xylose
      residues, indicating a higher content of xylo-oligosaccharides. CONCLUSIONS: This
      work revealed several changes in plant cell walls caused by deacetylation of
      xylan. We propose that deacetylated xylan is partially hydrolyzed in the cell
      walls, liberating xylo-oligosaccharides and their associated lignin oligomers
      from the cell wall network. Deacetylating xylan thus not only increases its
      susceptibility to hydrolytic enzymes during saccharification but also changes the
      cell wall architecture, increasing the extractability of lignin and xylan and
      facilitating saccharification.

PMID- 28428823
TI  - Combining manipulation of transcription factors and overexpression of the target
      genes to enhance lignocellulolytic enzyme production in Penicillium oxalicum.
AB  - BACKGROUND: Lignocellulolytic enzymes are the main enzymes to saccharify
      lignocellulose from renewable plant biomass in the bio-based economy. The
      production of these enzymes is transcriptionally regulated by multiple
      transcription factors. We previously engineered Penicillium oxalicum for improved
      cellulase production via manipulation of three genes in the cellulase expression
      regulatory network. However, the potential of combinational engineering of
      multiple regulators and their targets at protein abundance and activity levels
      has not been fully explored. RESULTS: Here, we verified that a point mutation
      XlnRA871V in transcription factor XlnR enhanced the expression of
      lignocellulolytic enzymes, particularly hemicellulases, in P. oxalicum. Then,
      overexpression of XlnRA871V with a constitutive PDE_02864 promoter was combined
      with the overexpression of cellulase transcriptional activator ClrB and deletion
      of carbon catabolite repressor CreA. The resulted strain RE-7 showed 8.9- and
      51.5-fold increased production of cellulase and xylanase relative to the starting
      strain M12, respectively. Further overexpression of two major cellulase genes
      cbh1-2 and eg1 enabled an additional 13.0% improvement of cellulase production.
      In addition, XlnRA871V led to decreased production of beta-glucosidase and
      amylase, which could be attributed to the reduced transcription of corresponding
      enzyme-encoding genes. CONCLUSIONS: The results illustrated that combinational
      manipulation of the involved transcription factors and their target genes was a
      viable strategy for efficient production of lignocellulolytic enzymes in
      filamentous fungi. The striking negative effect of XlnRA871V mutation on amylase
      production was also highlighted.

PMID- 28428824
TI  - Severe mycosis as a rare infection after a corn auger injury of the hand: a case
      report.
AB  - Mucormycosis is a rare but serious infection that can be seen in immunocompetent
      individuals who experience traumatic injury. The authors report a case in a 28
      year-old man who sustained a mangling hand injury in a corn augur accident. After
      initial aggressive debridement ongoing tissue necrosis was seen, and in
      subsequent biopsies invasive mucormycosis was diagnosed. The patient was
      successfully managed with immediate surgical debridement and antifungal
      medication and showed no sign of infection at six-month follow-up.

PMID- 28428826
TI  - The reliability of shear elastic modulus measurement of the ankle plantar flexion
      muscles is higher at dorsiflexed position of the ankle.
AB  - BACKGROUND: Excessive stiffness of lower limb muscles is associated with sports
      injuries. Therefore, the identification of a reliable measurement of the shear
      elastic modulus of various ankle plantar flexion muscles is required to evaluate
      lower leg sports injuries. This study investigated the reliable measurement of
      the shear elastic modulus of the ankle plantar flexion muscles at different ankle
      positions. METHODS: Twenty-three healthy young men (25.3 +/- 3.6 years, 172.9 +/-
      5.0 cm, 67.2 +/- 7.2 kg) participated in this study. The shear elastic moduli of
      the ankle plantar flexion muscles including the lateral gastrocnemius, medial
      gastrocnemius, soleus, peroneus longus, peroneus brevis, flexor hallucis longus,
      flexor digitorum longus and tibialis posterior were measured using ultrasonic
      shear wave elastography at 0, 10 and 20 degrees  dorsiflexion. RESULTS: The
      reliability of the shear elastic modulus measurements for each ankle position was
      assessed. The results showed that the interday reliability of the measurements
      differed between ankle positions and that the reliability of the shear elastic
      modulus measurements at 20 degrees  dorsiflexion was higher than that at 10
      degrees  or 0 degrees . CONCLUSION: Our results suggest that measurements at 20
      degrees  dorsiflexion may provide a more reliable measurement of the shear
      elastic modulus of ankle plantar flexion muscles.

PMID- 28428825
TI  - Comprehensive evaluation of genome-wide 5-hydroxymethylcytosine profiling
      approaches in human DNA.
AB  - BACKGROUND: The discovery that 5-methylcytosine (5mC) can be oxidized to 5
      hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has
      prompted wide interest in the potential role of 5hmC in reshaping the mammalian
      DNA methylation landscape. The gold-standard bisulphite conversion technologies
      to study DNA methylation do not distinguish between 5mC and 5hmC. However, new
      approaches to mapping 5hmC genome-wide have advanced rapidly, although it is
      unclear how the different methods compare in accurately calling 5hmC. In this
      study, we provide a comparative analysis on brain DNA using three 5hmC genome
      wide approaches, namely whole-genome bisulphite/oxidative bisulphite sequencing
      (WG Bis/OxBis-seq), Infinium HumanMethylation450 BeadChip arrays coupled with
      oxidative bisulphite (HM450K Bis/OxBis) and antibody-based immunoprecipitation
      and sequencing of hydroxymethylated DNA (hMeDIP-seq). We also perform loci
      specific TET-assisted bisulphite sequencing (TAB-seq) for validation of candidate
      regions. RESULTS: We show that whole-genome single-base resolution approaches are
      advantaged in providing precise 5hmC values but require high sequencing depth to
      accurately measure 5hmC, as this modification is commonly in low abundance in
      mammalian cells. HM450K arrays coupled with oxidative bisulphite provide a cost
      effective representation of 5hmC distribution, at CpG sites with 5hmC levels
      >~10%. However, 5hmC analysis is restricted to the genomic location of the
      probes, which is an important consideration as 5hmC modification is commonly
      enriched at enhancer elements. Finally, we show that the widely used hMeDIP-seq
      method provides an efficient genome-wide profile of 5hmC and shows high
      correlation with WG Bis/OxBis-seq 5hmC distribution in brain DNA. However, in
      cell line DNA with low levels of 5hmC, hMeDIP-seq-enriched regions are not
      detected by WG Bis/OxBis or HM450K, either suggesting misinterpretation of 5hmC
      calls by hMeDIP or lack of sensitivity of the latter methods. CONCLUSIONS: We
      highlight both the advantages and caveats of three commonly used genome-wide 5hmC
      profiling technologies and show that interpretation of 5hmC data can be
      significantly influenced by the sensitivity of methods used, especially as the
      levels of 5hmC are low and vary in different cell types and different genomic
      locations.

PMID- 28428827
TI  - Fundamental research on the action mechanism of the 800 nm semiconductor laser on
      skin blackheads and coarse pores.
AB  - The aim of the study was to determine the mechanism of action of the 800 nm
      semiconductor laser on skin blackheads and coarse pores. A total of 24 healthy
      purebred short-haired male guinea pigs, weighing 350-400 g, were selected and
      smeared with 0.5 ml coal tar suspension evenly by injector once daily. Treatment
      was continued for 14 days to form an experimental area of 8*3 cm on the back of
      the guinea pigs. The animals were divided into the following groups: Normal
      control group (NC), low-dose laser treatment group (L-LS), high-dose laser
      treatment group (H-LS), and Q-switched Nd:YAG treatment group (QC). Samples were
      extracted 1, 7 and 14 days after surgery and hematoxylin and eosin staining was
      used to identify the following: Epidermis, dermis, sebaceous gland change and
      hair follicle damage; the expression of proliferating cell nuclear antigen (PCNA)
      of sebaceous gland cells using immunohistochemistry; sebaceous gland cell
      apoptosis using TUNEL; and the protein expression of caspase-3, Bax and Bcl-2
      using western blot analysis. With the extension of time, we observed inflammatory
      cell infiltration, an increase in hair follicle distortion and necrosis of the
      surrounding hair follicles. The expression levels of PCNA of the L-LS, H-LS and
      QC groups decreased with time. Regarding the respective time points, the NC group
      was highest, the L-LS and H-LS groups were next highest and the H-LS group was
      lowest. The difference was statistically significant (P<0.05). The apoptotic rate
      of the L-LS, H-LS and QC groups increased with time. With regard to the
      respective time points, the NC group was lowest, the L-LS and QC groups were next
      lowest and the H-LS group was highest. The difference was statistically
      significant (P<0.05). The protein expression of caspase-3, Bax and Bcl-2 of the L
      LS, H-LS and QC groups increased with time. Regarding the respective time points,
      caspase-3 and Bax protein expression of the NC group was lowest, the L-LS and QC
      groups were next lowest and the H-LS group was highest. Bcl-2 protein expression
      of the NC group was highest, protein expression of the NC group was next highest
      and the H-LS group was lowest. The difference was statistically significant
      (P<0.05). In conclusion, the low-dose 800 nm semiconductor laser is an effective
      treatment on skin blackheads and coarse pores, and promotes hair follicle cell
      apoptosis without reducing the expression of PCNA.

PMID- 28428829
TI  - Semivariogram Analysis of Bone Images Implemented on FPGA Architectures.
AB  - Osteoporotic fractures are a major concern for the healthcare of elderly and
      female populations. Early diagnosis of patients with a high risk of osteoporotic
      fractures can be enhanced by introducing second-order statistical analysis of
      bone image data using techniques such as variogram analysis. Such analysis is
      computationally intensive thereby creating an impediment for introduction into
      imaging machines found in common clinical settings. This paper investigates the
      fast implementation of the semivariogram algorithm, which has been proven to be
      effective in modeling bone strength, and should be of interest to readers in the
      areas of computer-aided diagnosis and quantitative image analysis. The
      semivariogram is a statistical measure of the spatial distribution of data, and
      is based on Markov Random Fields (MRFs). Semivariogram analysis is a
      computationally intensive algorithm that has typically seen applications in the
      geosciences and remote sensing areas. Recently, applications in the area of
      medical imaging have been investigated, resulting in the need for efficient real
      time implementation of the algorithm. A semi-variance, gamma(h), is defined as
      the half of the expected squared differences of pixel values between any two data
      locations with a lag distance of h. Due to the need to examine each pair of
      pixels in the image or sub-image being processed, the base algorithm complexity
      for an image window with n pixels is O (n2) Field Programmable Gate Arrays
      (FPGAs) are an attractive solution for such demanding applications due to their
      parallel processing capability. FPGAs also tend to operate at relatively modest
      clock rates measured in a few hundreds of megahertz. This paper presents a
      technique for the fast computation of the semivariogram using two custom FPGA
      architectures. A modular architecture approach is chosen to allow for replication
      of processing units. This allows for high throughput due to concurrent processing
      of pixel pairs. The current implementation is focused on isotropic semivariogram
      computations only. The algorithm is benchmarked using VHDL on a Xilinx XUPV5
      LX110T development Kit, which utilizes the Virtex5 FPGA. Medical image data from
      DXA scans are utilized for the experiments. Implementation results show that a
      significant advantage in computational speed is attained by the architectures
      with respect to implementation on a personal computer with an Intel i7 multi-core
      processor.

PMID- 28428828
TI  - Bioinformatics analysis of key genes and latent pathway interactions based on the
      anaplastic thyroid carcinoma gene expression profile.
AB  - Anaplastic thyroid carcinoma (ATC) is an aggressive malignant disease in older
      adults with a high mortality rate. The present study aimed to examine several key
      genes and pathways, which are associated with ATC. The GSE33630 gene expression
      profile was downloaded from the Gene Expression Omnibus database, which included
      11 ATC and 45 normal thyroid samples. The differentially expressed genes (DEGs)
      in ATC were identified using the Limma package in R. The Gene Ontology functions
      and Kyoto Encyclopedia of Genes and Genomes pathways of the selected DEGs were
      enriched using the Database for Annotation, Visualization and Integrated
      Discovery. A protein-protein interaction (PPI) network of the DEGs was
      constructed to select significant modules. Furthermore, a latent pathway
      interactive network was constructed to select the significant pathways associated
      with ATC. A total of 665 DEGs in the ATC samples were screened, and four
      significant modules were selected from the PPI network. The DEGs in the four
      modules were enriched in several functions and pathways. In addition, 29
      significant pathways associated with ATC were selected, and he Toll-like receptor
      (TLR) signaling pathway, extracellular matrix (ECM)-receptor interaction and
      cytokine-cytokine interaction pathway were identified as important pathways. FBJ
      murine osteosarcoma viral oncogene homolog (FOS), chemokine C-X-C motif ligand 10
      (CXCL10), collagen type V alpha1 (COL5A1) and chemokine (C-C motif) ligand 28
      (CCL28) were the key DEGs involved in these significant pathways. The data
      obtained in the present study revealed that the TLR signaling pathway, ECM
      receptor interaction and cytokine-cytokine receptor interaction pathway, and the
      FOS, CXCL10, COL5A1, COL11A1 and CCL28 genes have different roles in the
      progression of ATC, and these may be used as therapeutic targets for ATC.

PMID- 28428830
TI  - Generalized Alternating Direction Method of Multipliers: New Theoretical Insights
      and Applications.
AB  - Recently, the alternating direction method of multipliers (ADMM) has received
      intensive attention from a broad spectrum of areas. The generalized ADMM (GADMM)
      proposed by Eckstein and Bertsekas is an efficient and simple acceleration scheme
      of ADMM. In this paper, we take a deeper look at the linearized version of GADMM
      where one of its subproblems is approximated by a linearization strategy. This
      linearized version is particularly efficient for a number of applications arising
      from different areas. Theoretically, we show the worst-case ??(1/k) convergence
      rate measured by the iteration complexity (k represents the iteration counter) in
      both the ergodic and a nonergodic senses for the linearized version of GADMM.
      Numerically, we demonstrate the efficiency of this linearized version of GADMM by
      some rather new and core applications in statistical learning. Code packages in
      Matlab for these applications are also developed.

PMID- 28428831
TI  - Cord blood hematopoietic cells from preterm infants display altered DNA
      methylation patterns.
AB  - BACKGROUND: Premature infants are highly vulnerable to infection. This is partly
      attributable to the preterm immune system, which differs from that of the term
      neonate in cell composition and function. Multiple studies have found
      differential DNA methylation (DNAm) between preterm and term infants' cord blood;
      however, interpretation of these studies is limited by the confounding factor of
      blood cell composition. This study evaluates the epigenetic impact of preterm
      birth in isolated hematopoietic cell populations, reducing the concern of cell
      composition differences. METHODS: Genome-wide DNAm was measured using the
      Illumina 450K array in T cells, monocytes, granulocytes, and nucleated red blood
      cells (nRBCs) isolated from cord blood of 5 term and 5 preterm (<31 weeks
      gestational age) newborns. DNAm of hematopoietic cells was compared globally
      across the 450K array and through site-specific linear modeling. RESULTS:
      Nucleated red blood cells (nRBCs) showed the most extensive changes in DNAm, with
      9258 differentially methylated (DM) sites (FDR < 5%, |Deltabeta| > 0.10)
      discovered between preterm and term infants compared to the <1000 prematurity-DM
      sites identified in white blood cell populations. The direction of DNAm change
      with gestational age at these prematurity-DM sites followed known patterns of
      hematopoietic differentiation, suggesting that term hematopoietic cell
      populations are more epigenetically mature than their preterm counterparts.
      Consistent shifts in DNAm between preterm and term cells were observed at 25 CpG
      sites, with many of these sites located in genes involved in growth and
      proliferation, hematopoietic lineage commitment, and the cytoskeleton. DNAm in
      preterm and term hematopoietic cells conformed to previously identified DNAm
      signatures of fetal liver and bone marrow, respectively. CONCLUSIONS: This study
      presents the first genome-wide mapping of epigenetic differences in hematopoietic
      cells across the late gestational period. DNAm differences in hematopoietic cells
      between term and <31 weeks were consistent with the hematopoietic origin of these
      cells during ontogeny, reflecting an important role of DNAm in their regulation.
      Due to the limited sample size and the high coincidence of prematurity and
      multiple births, the relationship between cause of preterm birth and DNAm could
      not be evaluated. These findings highlight gene regulatory mechanisms at both
      cell-specific and systemic levels that may be involved in fetal immune system
      maturation.

PMID- 28428832
TI  - A meta-analysis testing eusocial co-option theories in termite gut physiology and
      symbiosis.
AB  - The termite gut accomplishes key physiologic functions that underlie termite
      symbiosis and sociality. However, potential candidate functions of the host
      symbiont holobiome have not yet been explored across seemingly divergent
      processes such as digestion, immunity, caste differentiation, and xenobiotic
      tolerance. This study took a meta-analysis approach for concurrently studying
      host and symbiont gut metatranscriptome responses of the lower termite
      Reticulitermes flavipes, which has ancestral characteristics and hosts a diverse
      mix of eukaryotic and bacterial symbionts. Thirteen treatments were compared from
      5 categories (dietary, social, hormonal, immunological, and xenobiotic),
      revealing 3 main insights. First, each of the 5 tested colonies had distinct
      magnitudes of transcriptome response, likely as a result of unique symbiont
      profiles, which highlights the uniqueness of individual termite colonies. Second,
      after normalization to standardize colony response magnitudes, unique treatment
      linked metatranscriptome topologies became apparent. Third, despite colony and
      topology differences, 4 co-opted master genes emerged that were universally
      responsive across diverse treatments. These master genes encode host functions
      related to protein translation and symbiont functions related to protein
      degradation and pore formation in microbial cell walls. Three of the 4 master
      genes were from co-evolved protist symbionts, highlighting potentially co-evolved
      roles for gut symbiota in coordinating functional responses of the collective
      host-symbiont holobiome. Lastly, for host genes identified, these results provide
      annotations of recent termite genome sequences. By revealing conserved domain
      genes, as well as apparent roles for gut symbiota in holobiome regulation, this
      study provides new insights into co-opted eusocial genes and symbiont roles in
      termite sociobiology.

PMID- 28428833
TI  - Complete genome sequence of Kosakonia oryzae type strain Ola 51T.
AB  - Strain Ola 51T (=LMG 24251T = CGMCC 1.7012T) is the type strain of the species
      Kosakonia oryzae and was isolated from surface-sterilized roots of the wild rice
      species Oryza latifolia grown in Guangdong, China. Here we summarize the features
      of the strain Ola 51T and describe its complete genome sequence. The genome
      contains one circular chromosome of 5,303,342 nucleotides with 54.01% GC content,
      4773 protein-coding genes, 16 rRNA genes, 76 tRNA genes, 13 ncRNA genes, 48
      pseudo genes, and 1 CRISPR array.

PMID- 28428834
TI  - Genome sequencing and analysis of Ralstonia solanacearum phylotype I strains FJAT
      91, FJAT-452 and FJAT-462 isolated from tomato, eggplant, and chili pepper in
      China.
AB  - Ralstonia solanacearum is an extremely destructive pathogen able to cause disease
      in a wide range of host plants. Here we report the draft genome sequences of the
      strains FJAT-91, FJAT-452 and FJAT-462, isolated from tomato, eggplant, and chili
      pepper, respectively, in China. In addition to the genome annotation, we
      performed a search for type-III secreted effectors in these strains, providing a
      detailed annotation of their presence and distinctive features compared to the
      effector repertoire of the reference phylotype I strain (GMI1000). In this
      analysis, we found that each strain has a unique effector repertoire, encoding
      both strain-specific effector variants and variations shared among all three
      strains. Our study, based on strains isolated from different hosts within the
      same geographical location, provides insight into effector repertoires sufficient
      to cause disease in different hosts, and may contribute to the identification of
      host specificity determinants for R. solanacearum.

PMID- 28428835
TI  - Aqueous Plasma Pharmacy: Preparation Methods, Chemistry, and Therapeutic
      Applications.
AB  - Plasma pharmacy is a subset of the broader field of plasma medicine. Although not
      strictly defined, the term aqueous plasma pharmacy (APP) is used to refer to the
      generation and distribution of reactive plasma-generated species in an aqueous
      solution followed by subsequent administration for therapeutic benefits. APP
      attempts to harness the therapeutic effects of plasma-generated oxidant species
      within aqueous solution in various applications, such as disinfectant solutions,
      cell proliferation related to wound healing, and cancer treatment. The subsequent
      use of plasma-generated solutions in the APP approach facilitates the delivery of
      reactive plasma species to internal locations within the body. Although
      significant efforts in the field of plasma medicine have concentrated on
      employing direct plasma plume exposure to cells or tissues, here we focus
      specifically on plasma discharge in aqueous solution to render the solution
      biologically active for subsequent application. Methods of plasma discharge in
      solution are reviewed, along with aqueous plasma chemistry and the applications
      for APP. The future of the field also is discussed regarding necessary research
      efforts that will enable commercialization for clinical deployment.

PMID- 28428836
TI  - Muscle function and fatigability of trunk flexors in males and females.
AB  - BACKGROUND: Optimal function of the abdominal muscles is necessary for several
      life functions including lifting and carrying tasks. Sex differences in strength
      and fatigability are established for many limb muscles and back extensor muscles,
      but it is unknown if sex differences exist for the abdominal muscles despite
      their functional importance. METHODS: Eighteen females (24.3 +/- 4.8 years) and
      15 males (24.1 +/- 6.6 years) performed (1) isometric trunk flexion maximal
      voluntary contractions (MVCs) in a range of trunk positions to establish a torque
      angle curve and (2) submaximal (50% MVC), intermittent isometric contraction (6 s
      on, 4 s off) until task failure to determine fatigability of the trunk flexor
      muscles. Dual X-ray absorptiometry quantified body fat and lean mass. Physical
      activity levels were quantified with a questionnaire. Torque-angle curves,
      electromyography (EMG), MVC torque, and torque steadiness were compared with
      repeated measures ANOVA with sex as a between-subjects factor. RESULTS: For the
      torque-angle curve, MVC torque was reduced as the trunk angle increased toward
      flexion (p < 0.001). Males had greater MVC torque than females at the extended
      positions (31% difference), with no sex differences in torque in upright sitting
      (p > 0.05). Time-to-task failure for the submaximal fatigability task in upright
      sitting was similar between males and females (12.4 +/- 7 vs 10.5 +/- 6 min).
      Time-to-task failure was positively associated with strength (r = 0.473, p =
      0.005) and self-reported physical activity (r = 0.456, p = 0.030). Lean mass in
      the trunk was positively associated with trunk flexor strength (r = 0.378, p =
      0.011) and self-reported physical activity (r = 0.486, p = 0.007). Finally,
      torque steadiness [coefficient of variation of torque (CV)] during submaximal
      isometric contractions decreased with contraction intensity and was similar for
      males and females across all intensities. CONCLUSIONS: Unlike many limb muscle
      groups, males and females had similar fatigability and torque steadiness of the
      trunk flexor muscles during isometric contractions. Stronger individuals,
      however, exhibited less fatigability. Lower self-reported physical activity was
      associated with greater fatigability of trunk flexor muscles. The relationship
      between strength and fatigability of the trunk flexor muscles and physical
      activity supports the importance of abdominal muscle strengthening to offset
      fatigability in both males and females.

PMID- 28428837
TI  - Large is required for normal astrocyte migration and retinal vasculature
      development.
AB  - BACKGROUND: Persistent fetal vasculature (PFV) is a congenital developmental
      anomaly of the eye that accounts for about 5% of childhood blindness. The
      molecular mechanism of PFV remains unclear. As a glycosyltransferase of alpha
      dystroglycan, LARGE mutations have been found in congenital muscular dystrophy
      patients with brain abnormalities. Spontaneous Large mutant mice displayed
      similar symptoms of human muscle-eye-brain disorders. However, the detailed roles
      of Large in ocular vasculature development still need to be uncovered. RESULTS:
      In this paper, we report that a novel Large mutation generated by the piggyBac
      transposon insertion leads to PFV and abnormal retinal vasculature in mice.
      Glycosylation of alpha-DG, an essential component of the extracellular matrix,
      was significantly impaired in these Large mutants, leading to broken inner
      limiting membrane (ILM). As a guide of the retinal vasculature development, the
      distribution of retinal astrocytes became irregular within the retina, and many
      astrocytes abnormally migrated into the vitreous along with the hyaloid vessels
      in Large mutants. CONCLUSIONS: Large is essential for ILM formation and retinal
      astrocyte migration. The novel Large mutant mouse can serve as a new PFV model to
      further dissect LARGE functions in ocular vasculature development.

PMID- 28428838
TI  - A national strategic plan for reducing the burden of sexually transmitted
      infections in Israel by the year 2025.
AB  - BACKGROUND: There is on ongoing debate in the literature regarding the real
      burden of STIs (sexually transmitted infections) in Western countries and the
      proper strategies needed to estimate and to prevent them. Our purpose is to
      present an evidence-based national strategic plan for STI prevention in Israel
      through assessing the current burden of illness, leading international preventive
      strategies, and practical policymaking experience. METHODS: Epidemiologic and
      health policy data on STIs were analyzed from various sources: a) systematic
      national surveillance data for the years 2002-2014; b) the international
      scientific literature (published between 2002-16; keywords: Sexually Transmitted
      Diseases (STD) (or STI) AND prevention AND intervention AND gonorrhea OR
      chlamydia OR syphilis; c) internal Ministry of Health (MOH) analyses and reports,
      and d) expert opinion. RESULTS: Incidence rates in Israel of Chlamydia
      trachomatis (chlamydia), Neisseria gonorrhea (gonorrhea) and Treponema pallidum
      (syphilis) are lower than in most Western countries. However, rates vary among
      population subgroups: chlamydia, gonorrhea and syphilis are higher in Jews than
      in non-Jews, and this gap has increased for chlamydia over the past decade.
      Primary and secondary syphilis rates have increased among men having sex with men
      (MSM). It is likely that STIs are under-reported and that incidence is even
      rising due to migration. A key recommendation is the establishment of an active
      surveillance system of STIs, utilizing active case finding in high risk
      populations, along with regular contact with STI clinics run by the four national
      health management organizations and by the MoH. As with most European countries,
      the low prevalence of chlamydia and gonorrhea does not justify population-wide
      screening. Conversely, the increasing incidence of syphilis among MSM should lead
      to regular screening among this group. CONCLUSIONS: A national STIs prevention
      strategy for the year 2025 was presented. Although the current burden of illness
      is low relatively to other Western countries, this is thought to reflect a
      certain degree of underreporting. These and other gaps suggest a need for focused
      epidemiologic and health services research to better characterize health risk
      behaviors as well as provider practice patterns. Innovative implementation
      strategies have been described, together with the capacity building components
      needed for developing specific and implementable policy recommendations for the
      year 2025.

PMID- 28428841
TI  - Reproductive traits associated with species turnover of amphibians in Amazonia
      and its Andean slopes.
AB  - Assembly of ecological communities is important for the conservation of
      ecosystems, predicting perturbation impacts, and understanding the origin and
      loss of biodiversity. We tested how amphibian communities are assembled by
      neutral and niche-based mechanisms, such as habitat filtering. Species richness,
      beta-diversities, and reproductive traits of amphibians were evaluated at local
      scale in seven habitats at different elevation and disturbance levels in Wisui
      Biological Station, Morona-Santiago, Ecuador, on the foothills of the Cordillera
      del Kutuku; and at regional scale using 109 localities across evergreen forests
      of Amazonia and its Andean slopes (0-3,900 m a.s.l.). At local scale, species
      composition showed strong differences among habitats, explained mainly by
      turnover. Reproductive modes occurred differently across habitats (e.g.,
      prevalence of direct developers at high elevation, where breeding in ground level
      water disappears). At regional scale, elevation was the most important factor
      explaining the changes in species richness, reproductive trait occurrences, and
      biotic dissimilarities. Species number in all groups decreased with elevation
      except for those with lotic tadpoles and terrestrial reproduction stages.
      Seasonality, annual precipitation, and relative humidity partially explained the
      occurrence of some reproductive traits. Biotic dissimilarities were also mostly
      caused by turnover rather than nestedness and were particularly high in montane
      and foothill sites. Within lowlands, geographic distance explained more
      variability than elevation. Habitat filtering was supported by the different
      occurrence of reproductive traits according to elevation, water availability, and
      breeding microhabitats at both scales, as well as other assembly mechanisms based
      in biotic interactions at local scale. Human-generated land use changes in
      Amazonia and its Andean slopes reduce local amphibian biodiversity by alteration
      of primary forests and loss of their microhabitats and the interaction network
      that maintains their unique amphibian assemblages with different reproductive
      strategies.

PMID- 28428839
TI  - Population genomics meet Lagrangian simulations: Oceanographic patterns and long
      larval duration ensure connectivity among Paracentrotus lividus populations in
      the Adriatic and Ionian seas.
AB  - Connectivity between populations influences both their dynamics and the genetic
      structuring of species. In this study, we explored connectivity patterns of a
      marine species with long-distance dispersal, the edible common sea urchin
      Paracentrotus lividus, focusing mainly on the Adriatic-Ionian basins (Central
      Mediterranean). We applied a multidisciplinary approach integrating population
      genomics, based on 1,122 single nucleotide polymorphisms (SNPs) obtained from 2b
      RAD in 275 samples, with Lagrangian simulations performed with a biophysical
      model of larval dispersal. We detected genetic homogeneity among eight population
      samples collected in the focal Adriatic-Ionian area, whereas weak but significant
      differentiation was found with respect to two samples from the Western
      Mediterranean (France and Tunisia). This result was not affected by the few
      putative outlier loci identified in our dataset. Lagrangian simulations found a
      significant potential for larval exchange among the eight Adriatic-Ionian
      locations, supporting the hypothesis of connectivity of P. lividus populations in
      this area. A peculiar pattern emerged from the comparison of our results with
      those obtained from published P. lividus cytochrome b (cytb) sequences, the
      latter revealing genetic differentiation in the same geographic area despite a
      smaller sample size and a lower power to detect differences. The comparison with
      studies conducted using nuclear markers on other species with similar pelagic
      larval durations in the same Adriatic-Ionian locations indicates species-specific
      differences in genetic connectivity patterns and warns against generalizing
      single-species results to the entire community of rocky shore habitats.

PMID- 28428840
TI  - An Internet-based platform for the estimation of outcrossing potential between
      cultivated and Chilean vascular plants.
AB  - A national-scale study of outcrossing potential within Chilean vascular flora was
      conducted using an upgraded algorithm, which adds parameters such as pollinator
      agents, climate, and geographic conditions. Datasets were organized and linked in
      a Web platform (www.flujogenico.cl), in which the development of a total
      outcrossing potential (TOP) predictor was formulated. The TOP predictor is the
      engine in the Web platform, which models the effect of a type of agricultural
      practice on others (coexistence calculation mode) and on the environment
      (biodiversity calculation mode). The scale for TOP results uses quintiles in
      order to define outcrossing potential between species as "very low," "low,"
      "medium," "high," or "very high." In a coexistence analysis considering 256
      species (207 genera), the 10 highest TOP values were for genera Citrus, Prunus,
      Trifolium, Brassica, Allium, Eucalyptus, Cucurbita, Solanum, Lollium, and Lotus.
      The highest TOP for species in this analysis fell at "high" potential, 4.9% of
      the determined values. In biodiversity mode, seven out of 256 cultivated species
      (2.7%) were native, and 249 (97.3%) corresponded to introduced species. The
      highest TOP was obtained in the genera Senecio, Calceolaria, Viola, Solanum, Poa,
      Alstroemeria, Valeriana, Vicia, Atriplex, and Campanula, showing "high" potential
      in 4.9% of the values. On the other hand, 137 genetically modified species,
      including the commercial and pre-commercial developments, were included and
      represented 100 genera. Among these, 22 genera had relatives (i.e., members of
      the same genus) in the native/introduced group. The genera with the highest
      number of native/introduced relatives ranged from one (Ipomea, Limonium, Carica,
      Potentilla, Lotus, Castanea, and Daucus) to 66 species (Solanum). The highest TOP
      was obtained when the same species were coincident in both groups, such as for
      Carica chilensis, Prosopis tamarugo, and Solanum tuberosum. Results are discussed
      from the perspective of assessing the possible impact of cultivated species on
      Chilean flora biodiversity. The TOP predictor (http://epc.agroinformatica.cl/) is
      useful in the context of environmental risk assessment.

PMID- 28428842
TI  - Incipient ecological speciation between successional varieties of a dominant tree
      involves intrinsic postzygotic isolating barriers.
AB  - Whereas disruptive selection imposed by heterogeneous environments can lead to
      the evolution of extrinsic isolating barriers between diverging populations, the
      evolution of intrinsic postzygotic barriers through divergent selection is less
      certain. Long-lived species such as trees may be especially slow to evolve
      intrinsic isolating barriers. We examined postpollination reproductive isolating
      barriers below the species boundary, in an ephemeral hybrid zone between two
      successional varieties of the landscape-dominant Hawaiian tree, Metrosideros
      polymorpha, on volcanically active Hawai'i Island. These archipelago-wide
      sympatric varieties show the weakest neutral genetic divergence of any taxon pair
      on Hawai'i Island but significant morphological and ecological differentiation
      consistent with adaptation to new and old lava flows. Cross-fertility between
      varieties was high and included heterosis of F1 hybrids at the seed germination
      stage, consistent with a substantial genetic load apparent within varieties
      through low self-fertility and a lack of self-pollen discrimination. However, a
      partial, but significant, barrier was observed in the form of reduced female and
      male fertility of hybrids, especially backcross hybrids, consistent with the
      accumulation of genetic incompatibilities between varieties. These results
      suggest that partial intrinsic postzygotic barriers can arise through disruptive
      selection acting on large, hybridizing populations of a long-lived species.

PMID- 28428843
TI  - RAD sequencing reveals genomewide divergence between independent invasions of the
      European green crab (Carcinus maenas) in the Northwest Atlantic.
AB  - Genomic studies of invasive species can reveal both invasive pathways and
      functional differences underpinning patterns of colonization success. The
      European green crab (Carcinus maenas) was initially introduced to eastern North
      America nearly 200 years ago where it expanded northwards to eastern Nova Scotia.
      A subsequent invasion to Nova Scotia from a northern European source allowed
      further range expansion, providing a unique opportunity to study the invasion
      genomics of a species with multiple invasions. Here, we use restriction-site
      associated DNA sequencing-derived SNPs to explore fine-scale genomewide
      differentiation between these two invasions. We identified 9137 loci from green
      crab sampled from 11 locations along eastern North America and compared spatial
      variation to mitochondrial COI sequence variation used previously to characterize
      these invasions. Overall spatial divergence among invasions was high (pairwise
      FST ~0.001 to 0.15) and spread across many loci, with a mean FST ~0.052 and 52%
      of loci examined characterized by FST values >0.05. The majority of the most
      divergent loci (i.e., outliers, ~1.2%) displayed latitudinal clines in allele
      frequency highlighting extensive genomic divergence among the invasions.
      Discriminant analysis of principal components (both neutral and outlier loci)
      clearly resolved the two invasions spatially and was highly correlated with
      mitochondrial divergence. Our results reveal extensive cryptic intraspecific
      genomic diversity associated with differing patterns of colonization success and
      demonstrates clear utility for genomic approaches to delineating the distribution
      and colonization success of aquatic invasive species.

PMID- 28428844
TI  - Stable isotope analyses-A method to distinguish intensively farmed from wild
      frogs.
AB  - Consumption of frog legs is increasing worldwide, with potentially dramatic
      effects for ecosystems. More and more functioning frog farms are reported to
      exist. However, due to the lack of reliable methods to distinguish farmed from
      wild-caught individuals, the origin of frogs in the international trade is often
      uncertain. Here, we present a new methodological approach to this problem. We
      investigated the isotopic composition of legally traded frog legs from suppliers
      in Vietnam and Indonesia. Muscle and bone tissue samples were examined for
      delta15N, delta13C, and delta18O stable isotope compositions, to elucidate the
      conditions under which the frogs grew up. We used DNA barcoding (16S rRNA) to
      verify species identities. We identified three traded species (Hoplobatrachus
      rugulosus, Fejervarya cancrivora and Limnonectes macrodon); species identities
      were partly deviating from package labeling. Isotopic values of delta15N and
      delta18O showed significant differences between species and country of origin.
      Based on low delta15N composition and generally little variation in stable
      isotope values, our results imply that frogs from Vietnam were indeed farmed. In
      contrast, the frogs from the Indonesian supplier likely grew up under natural
      conditions, indicated by higher delta15N values and stronger variability in the
      stable isotope composition. Our results indicate that stable isotope analyses
      seem to be a useful tool to distinguish between naturally growing and intensively
      farmed frogs. We believe that this method can be used to improve the control in
      the international trade of frog legs, as well as for other biological products,
      thus supporting farming activities and decreasing pressure on wild populations.
      However, we examined different species from different countries and had no access
      to samples of individuals with confirmed origin and living conditions. Therefore,
      we suggest improving this method further with individuals of known origin and
      history, preferably including samples of the respective nutritive bases.

PMID- 28428846
TI  - Long-term and widespread changes in agricultural practices influence ring-necked
      pheasant abundance in California.
AB  - Declines in bird populations in agricultural regions of North America and Europe
      have been attributed to agricultural industrialization, increases in use of
      agrochemical application, and increased predation related to habitat
      modification. Based on count data compiled from Breeding Bird Survey (BBS) from
      1974 to 2012, Christmas Bird Count (CBC) collected from 1914 to 2013, and hunter
      data from Annual Game Take Survey (AGTS) for years 1948-2010, ring-necked
      pheasants (Phasianus colchicus) in California have experienced substantial
      declines in agricultural environments. Using a modeling approach that integrates
      all three forms of survey data into a joint response abundance index, we found
      pheasant abundance was related to the amount of harvested and unharvested crop
      land, types of crops produced, amount of total pesticide applied, minimum
      temperature, precipitation, and numbers of avian competitors and predators.
      Specifically, major changes in agricultural practices over the last three decades
      were associated with declines in pheasant numbers and likely reflected widespread
      loss of habitat. For example, increases in cropland were associated with
      increased pheasant abundance during early years of study but this effect
      decreased through time, such that no association in recent years was evidenced. A
      post hoc analysis revealed that crops beneficial to pheasant abundance (e.g.,
      barley) have declined substantially in recent decades and were replaced by less
      advantageous crops (e.g., nut trees). An additional analysis using a restricted
      data set (1990-2013) indicated recent negative impacts on pheasant numbers
      associated with land use practices were also associated with relatively high
      levels of pesticide application. Our results may provide valuable information for
      management policies aimed at reducing widespread declines in pheasant populations
      in California and may be applicable to other avian species within agricultural
      settings. Furthermore, this general analytical approach is not limited to
      pheasants and could be applied to other taxa for which multiple survey data
      sources exist.

PMID- 28428845
TI  - Global pattern of plant utilization across different organisms: Does plant
      apparency or plant phylogeny matter?
AB  - The present study is the first to consider human and nonhuman consumers together
      to reveal several general patterns of plant utilization. We provide evidence that
      at a global scale, plant apparency and phylogenetic isolation can be important
      predictors of plant utilization and consumer diversity. Using the number of
      species or genera or the distribution area of each plant family as the island
      "area" and the minimum phylogenetic distance to common plant families as the
      island "distance", we fitted presence-area relationships and presence-distance
      relationships with a binomial GLM (generalized linear model) with a logit link.
      The presence-absence of consumers among each plant family strongly depended on
      plant apparency (family size and distribution area); the diversity of consumers
      increased with plant apparency but decreased with phylogenetic isolation. When
      consumers extended their host breadth, unapparent plants became more likely to be
      used. Common uses occurred more often on common plants and their relatives,
      showing higher host phylogenetic clustering than uncommon uses. On the contrary,
      highly specialized uses might be related to the rarity of plant chemicals and
      were therefore very species-specific. In summary, our results provide a global
      illustration of plant-consumer combinations and reveal several general patterns
      of plant utilization across humans, insects and microbes. First, plant apparency
      and plant phylogenetic isolation generally govern plant utilization value, with
      uncommon and isolated plants suffering fewer parasites. Second, extension of the
      breadth of utilized hosts helps explain the presence of consumers on unapparent
      plants. Finally, the phylogenetic clustering structure of host plants is
      different between common uses and uncommon uses. The strength of such consistent
      plant utilization patterns across a diverse set of usage types suggests that the
      persistence and accumulation of consumer diversity and use value for plant
      species are determined by similar ecological and evolutionary processes.

PMID- 28428847
TI  - Lichen acclimation to changing environments: Photobiont switching vs. climate
      specific uniqueness in Psora decipiens.
AB  - Unraveling the complex relationship between lichen fungal and algal partners has
      been crucial in understanding lichen dispersal capacity, evolutionary processes,
      and responses in the face of environmental change. However, lichen symbiosis
      remains enigmatic, including the ability of a single fungal partner to associate
      with various algal partners. Psora decipiens is a characteristic lichen of
      biological soil crusts (BSCs), across semi-arid, temperate, and alpine biomes,
      which are particularly susceptible to habitat loss and climate change. The high
      levels of morphological variation found across the range of Psora decipiens may
      contribute to its ability to withstand environmental change. To investigate Psora
      decipiens acclimation potential, individuals were transplanted between four
      climatically distinct sites across a European latitudinal gradient for 2 years.
      The effect of treatment was investigated through a morphological examination
      using light and SEM microscopy; 26S rDNA and rbcL gene analysis assessed site
      specific relationships and lichen acclimation through photobiont switching.
      Initial analysis revealed that many samples had lost their algal layers. Although
      new growth was often determined, the algae were frequently found to have died
      without evidence of a new photobiont being incorporated into the thallus.
      Mycobiont analysis investigated diversity and determined that new growth was a
      part of the transplant, thus, revealing that four distinct fungal clades, closely
      linked to site, exist. Additionally, P. decipiens was found to associate with the
      green algal genus Myrmecia, with only two genetically distinct clades between the
      four sites. Our investigation has suggested that P. decipiens cannot acclimate to
      the substantial climatic variability across its environmental range.
      Additionally, the different geographical areas are home to genetically distinct
      and unique populations. The variation found within the genotypic and morpho
      physiological traits of P. decipiens appears to have a climatic determinant, but
      this is not always reflected by the algal partner. Although photobiont switching
      occurs on an evolutionary scale, there is little evidence to suggest an active
      environmentally induced response. These results suggest that this species, and
      therefore, other lichen species, and BSC ecosystems themselves may be
      significantly vulnerable to climate change and habitat loss.

PMID- 28428848
TI  - Modeling activity patterns of wildlife using time-series analysis.
AB  - The study of wildlife activity patterns is an effective approach to understanding
      fundamental ecological and evolutionary processes. However, traditional
      statistical approaches used to conduct quantitative analysis have thus far had
      limited success in revealing underlying mechanisms driving activity patterns.
      Here, we combine wavelet analysis, a type of frequency-based time-series
      analysis, with high-resolution activity data from accelerometers embedded in GPS
      collars to explore the effects of internal states (e.g., pregnancy) and external
      factors (e.g., seasonal dynamics of resources and weather) on activity patterns
      of the endangered giant panda (Ailuropoda melanoleuca). Giant pandas exhibited
      higher frequency cycles during the winter when resources (e.g., water and forage)
      were relatively poor, as well as during spring, which includes the giant panda's
      mating season. During the summer and autumn when resources were abundant, pandas
      exhibited a regular activity pattern with activity peaks every 24 hr. A pregnant
      individual showed distinct differences in her activity pattern from other giant
      pandas for several months following parturition. These results indicate that
      animals adjust activity cycles to adapt to seasonal variation of the resources
      and unique physiological periods. Wavelet coherency analysis also verified the
      synchronization of giant panda activity level with air temperature and solar
      radiation at the 24-hr band. Our study also shows that wavelet analysis is an
      effective tool for analyzing high-resolution activity pattern data and its
      relationship to internal and external states, an approach that has the potential
      to inform wildlife conservation and management across species.

PMID- 28428849
TI  - Species distribution models predict temporal but not spatial variation in forest
      growth.
AB  - Bioclimate envelope models have been widely used to illustrate the discrepancy
      between current species distributions and their potential habitat under climate
      change. However, the realism and correct interpretation of such projections has
      been the subject of considerable discussion. Here, we investigate whether climate
      suitability predictions correlate to tree growth, measured in permanent inventory
      plots and inferred from tree-ring records. We use the ensemble classifier
      RandomForest and species occurrence data from ~200,000 inventory plots to build
      species distribution models for four important European forestry species: Norway
      spruce, Scots pine, European beech, and pedunculate oak. We then correlate
      climate-based habitat suitability with volume measurements from ~50-year-old
      stands, available from ~11,000 inventory plots. Secondly, habitat projections
      based on annual historical climate are compared with ring width from ~300 tree
      ring chronologies. Our working hypothesis is that habitat suitability projections
      from species distribution models should to some degree be associated with
      temporal or spatial variation in these growth records. We find that the habitat
      projections are uncorrelated with spatial growth records (inventory plot data),
      but they do predict interannual variation in tree-ring width, with an average
      correlation of .22. Correlation coefficients for individual chronologies range
      from values as high as .82 or as low as -.31. We conclude that tree responses to
      projected climate change are highly site-specific and that local suitability of a
      species for reforestation is difficult to predict. That said, projected increase
      or decrease in climatic suitability may be interpreted as an average expectation
      of increased or reduced growth over larger geographic scales.

PMID- 28428850
TI  - Shortcuts in biodiversity research: What determines the performance of higher
      taxa as surrogates for species?
AB  - Biodiversity research is often impeded by the time and resources required to
      identify species. One possible solution is to use higher taxa to predict species
      richness and community composition. However, previous studies have shown that the
      performance of higher taxa as surrogates for species is highly variable, making
      it difficult to predict whether the method will be reliable for a particular
      objective. Using 8 independent datasets, I tested whether higher taxa accurately
      characterize the responses of beetle and ant communities to environmental
      drivers. For each dataset, ordinations were carried out using species and higher
      taxa, and the two compared using the Procrustes m2 statistic (a scale-independent
      variant of Procrustes sum of squares). I then modelled the relationship between
      five hypothesised explanatory variables and 1) Procrustes m2, and 2) the
      coefficient of determination (R2) for the correlation between richness of species
      and higher taxa. The species to higher taxon ratio, community structure, beta
      diversity, completeness of sampling, and taxon (beetles or ants) were all
      significant predictors of m2, together explaining 88% of the variance. The only
      significant predictor of R2 was the species to higher taxon ratio, which
      explained 45% of the variance. When using higher taxa to predict community
      composition, better performance is expected when the ratio of species to higher
      taxa is low, in communities with high evenness and high species turnover, and
      when there is niche conservation within higher taxa. When using higher taxa to
      predict species richness, effective surrogacy can be expected when the species to
      higher taxon ratio is very low. When it is not, surrogacy performance may be
      strongly influenced by stochastic factors, making predictions of performance
      difficult.

PMID- 28428851
TI  - Screening mitochondrial DNA sequence variation as an alternative method for
      tracking established and outbreak populations of Queensland fruit fly at the
      species southern range limit.
AB  - Understanding the relationship between incursions of insect pests and established
      populations is critical to implementing effective control. Studies of genetic
      variation can provide powerful tools to examine potential invasion pathways and
      longevity of individual pest outbreaks. The major fruit fly pest in eastern
      Australia, Queensland fruit fly Bactrocera tryoni (Froggatt), has been subject to
      significant long-term quarantine and population reduction control measures in the
      major horticulture production areas of southeastern Australia, at the species
      southern range limit. Previous studies have employed microsatellite markers to
      estimate gene flow between populations across this region. In this study, we used
      an independent genetic marker, mitochondrial DNA (mtDNA) sequences, to screen
      genetic variation in established and adjacent outbreak populations in
      southeastern Australia. During the study period, favorable environmental
      conditions resulted in multiple outbreaks, which appeared genetically distinctive
      and relatively geographically localized, implying minimal dispersal between
      simultaneous outbreaks. Populations in established regions were found to occur
      over much larger areas. Screening mtDNA (female) lineages proved to be an
      effective alternative genetic tool to assist in understanding fruit fly
      population dynamics and provide another possible molecular method that could now
      be employed for better understanding of the ecology and evolution of this and
      other pest species.

PMID- 28428852
TI  - Stoichiometric traits of stickleback: Effects of genetic background, rearing
      environment, and ontogeny.
AB  - Phenotypes can both evolve in response to, and affect, ecosystem change, but few
      examples of diverging ecosystem-effect traits have been investigated. Bony armor
      traits of fish are good candidates for this because they evolve rapidly in some
      freshwater fish populations, and bone is phosphorus rich and likely to affect
      nutrient recycling in aquatic ecosystems. Here, we explore how ontogeny, rearing
      environment, and bone allocation among body parts affect the stoichiometric
      phenotype (i.e., stoichiometric composition of bodies and excretion) of
      threespine stickleback. We use two populations from distinct freshwater lineages
      with contrasting lateral plating phenotypes (full vs. low plating) and their
      hybrids, which are mostly fully plated. We found that ontogeny, rearing
      environment, and body condition were the most important predictors of organismal
      stoichiometry. Although elemental composition was similar between both
      populations and their hybrids, we found significant divergence in phosphorus
      allocation among body parts and in phosphorus excretion rates. Overall, body
      armor differences did not explain variation in whole body phosphorus, phosphorus
      allocation, or phosphorus excretion. Evolutionary divergence between these
      lineages in both allocation and excretion is likely to have important direct
      consequences for ecosystems, but may be mediated by evolution of multiple
      morphological or physiological traits beyond plating phenotype.

PMID- 28428853
TI  - Coral reef mesopredators switch prey, shortening food chains, in response to
      habitat degradation.
AB  - Diet specificity is likely to be the key predictor of a predator's vulnerability
      to changing habitat and prey conditions. Understanding the degree to which
      predatory coral reef fishes adjust or maintain prey choice, in response to
      declines in coral cover and changes in prey availability, is critical for
      predicting how they may respond to reef habitat degradation. Here, we use stable
      isotope analyses to characterize the trophic structure of predator-prey
      interactions on coral reefs of the Keppel Island Group on the southern Great
      Barrier Reef, Australia. These reefs, previously typified by exceptionally high
      coral cover, have recently lost much of their coral cover due to coral bleaching
      and frequent inundation by sediment-laden, freshwater flood plumes associated
      with increased rainfall patterns. Long-term monitoring of these reefs
      demonstrates that, as coral cover declined, there has been a decrease in prey
      biomass, and a shift in dominant prey species from pelagic plankton-feeding
      damselfishes to territorial benthic algal-feeding damselfishes, resulting in
      differences in the principal carbon pathways in the food web. Using isotopes, we
      tested whether this changing prey availability could be detected in the diet of a
      mesopredator (coral grouper, Plectropomus maculatus). The delta13C signature in
      grouper tissue in the Keppel Islands shifted from a more pelagic to a more
      benthic signal, demonstrating a change in carbon sources aligning with the change
      in prey availability due to habitat degradation. Grouper with a more benthic
      carbon signature were also feeding at a lower trophic level, indicating a
      shortening in food chains. Further, we found a decline in the coral grouper
      population accompanying a decrease in total available prey biomass. Thus, while
      the ability to adapt diets could ameliorate the short-term impacts of habitat
      degradation on mesopredators, long-term effects may negatively impact
      mesopredator populations and alter the trophic structure of coral reef food webs.

PMID- 28428854
TI  - Not all weeds are created equal: A database approach uncovers differences in the
      sexual system of native and introduced weeds.
AB  - Weedy species provide excellent opportunities to examine the process of
      successful colonization of novel environments. Despite the influence of the
      sexual system on a variety of processes from reproduction to genetic structure,
      how the sexual system of species influences weediness has received only limited
      consideration. We examined the hypothesis that weedy plants have an increased
      likelihood of being self-compatible compared with nonweedy plants; this
      hypothesis is derived from Baker's law, which states that species that can
      reproduce uniparentally are more likely to successfully establish in a new
      habitat where mates are lacking. We combined a database of the weed
      (weedy/nonweedy) and introduction status (introduced/native) of plant species
      found in the USA with a database of plant sexual systems and determined whether
      native and introduced weeds varied in their sexual systems compared with native
      and introduced nonweeds. We found that introduced weeds are overrepresented by
      species with both male and female functions present within a single flower
      (hermaphrodites) whereas weeds native to the USA are overrepresented by species
      with male and female flowers present on a single plant (monoecious species).
      Overall, our results show that Baker's law is supported at the level of the
      sexual system, thus providing further evidence that uniparental reproduction is
      an important component of being either a native or introduced weed.

PMID- 28428855
TI  - Conditions on the Mexican moulting grounds influence feather colour and
      carotenoids in Bullock's orioles (Icterus bullockii).
AB  - Carotenoid-based plumage coloration plays a critical role for both inter- and
      intrasexual communication. Habitat and diet during molt can have important
      consequences for the development of the ornamental signals used in these
      contexts. When molt occurs away from the breeding grounds (e.g., pre-alternate
      molt on the wintering grounds, or stopover molt), discerning the influence of
      habitat and diet can be particularly important, as these effects may result in
      important carryover effects that influence territory acquisition or mate choice
      in subsequent seasons. Several species of songbirds in western North America,
      including the Bullock's oriole (Icterus bullockii), migrate from the breeding
      grounds to undergo a complete prebasic (post-breeding) molt at a stopover site in
      the region affected by the Mexican monsoon climate pattern. This strategy appears
      to have evolved several times independently in response to the harsh, food
      limited late-summer conditions in the arid West, which contrast strongly with the
      high productivity driven by heavy rains that is characteristic of the Mexican
      monsoon region. Within this region, individuals may be able to optimize plumage
      coloration by molting in favourable areas characterized by high resource
      abundance. We used stable isotope analysis (delta13C, delta15N) to ask whether
      the diet and molt habitat/location of Bullock's orioles influenced their
      expression of carotenoid-based plumage coloration as well as plumage carotenoid
      content and composition. Bullock's orioles with lower feather delta15N values
      acquired more colorful plumage (orange-shifted hue) but had feathers with lower
      total carotenoid concentration, lower zeaxanthin concentration, and marginally
      lower canthaxanthin and lutein concentration. Examining factors occurring
      throughout the annual cycle are critical for understanding evolutionary and
      ecological processes. Here, we demonstrate that conditions experienced during a
      stopover molt, occurring hundreds to thousands of kilometers from the breeding
      grounds, influence the production of ornamental plumage coloration, which may
      carryover to influence inter- and intrasexual signaling in subsequent seasons.

PMID- 28428856
TI  - Forage plants of an Arctic-nesting herbivore show larger warming response in
      breeding than wintering grounds, potentially disrupting migration phenology.
AB  - During spring migration, herbivorous waterfowl breeding in the Arctic depend on
      peaks in the supply of nitrogen-rich forage plants, following a "green wave" of
      grass growth along their flyway to fuel migration and reproduction. The effects
      of climate warming on forage plant growth are expected to be larger at the Arctic
      breeding grounds than in temperate wintering grounds, potentially disrupting this
      green wave and causing waterfowl to mistime their arrival on the breeding
      grounds. We studied the potential effect of climate warming on timing of food
      peaks along the migratory flyway of the Russian population of barnacle geese
      using a warming experiment with open-top chambers. We measured the effect of 1.0
      1.7 degrees C experimental warming on forage plant biomass and nitrogen
      concentration at three sites along the migratory flyway (temperate wintering
      site, temperate spring stopover site, and Arctic breeding site) during 2 months
      for two consecutive years. We found that experimental warming increased biomass
      accumulation and sped up the decline in nitrogen concentration of forage plants
      at the Arctic breeding site but not at temperate wintering and stop-over sites.
      Increasing spring temperatures in the Arctic will thus shorten the food peak of
      nitrogen-rich forage at the breeding grounds. Our results further suggest an
      advance of the local food peak in the Arctic under 1-2 degrees C climate warming,
      which will likely cause migrating geese to mistime their arrival at the breeding
      grounds, particularly considering the Arctic warms faster than the temperate
      regions. The combination of a shorter food peak and mistimed arrival is likely to
      decrease goose reproductive success under climate warming by reducing growth and
      survival of goslings after hatching.

PMID- 28428857
TI  - How repeatable is the Environmental Impact Classification of Alien Taxa (EICAT)?
      Comparing independent global impact assessments of amphibians.
AB  - The magnitude of impacts some alien species cause to native environments makes
      them targets for regulation and management. However, which species to target is
      not always clear, and comparisons of a wide variety of impacts are necessary.
      Impact scoring systems can aid management prioritization of alien species. For
      such tools to be objective, they need to be robust to assessor bias. Here, we
      assess the newly proposed Environmental Impact Classification for Alien Taxa
      (EICAT) used for amphibians and test how outcomes differ between assessors. Two
      independent assessments were made by Kraus (Annual Review of Ecology Evolution
      and Systematics, 46, 2015, 75-97) and Kumschick et al. (Neobiota, 33, 2017, 53
      66), including independent literature searches for impact records. Most of the
      differences between these two classifications can be attributed to different
      literature search strategies used with only one-third of the combined number of
      references shared between both studies. For the commonly assessed species, the
      classification of maximum impacts for most species is similar between assessors,
      but there are differences in the more detailed assessments. We clarify one
      specific issue resulting from different interpretations of EICAT, namely the
      practical interpretation and assigning of disease impacts in the absence of
      direct evidence of transmission from alien to native species. The differences
      between assessments outlined here cannot be attributed to features of the scheme.
      Reporting bias should be avoided by assessing all alien species rather than only
      the seemingly high-impacting ones, which also improves the utility of the data
      for management and prioritization for future research. Furthermore, assessments
      of the same taxon by various assessors and a structured review process for
      assessments, as proposed by Hawkins et al. (Diversity and Distributions, 21,
      2015, 1360), can ensure that biases can be avoided and all important literature
      is included.

PMID- 28428859
TI  - Species partitioning in a temperate mountain chain: Segregation by habitat vs.
      interspecific competition.
AB  - Disentangling the relative influence of the environment and biotic interactions
      in determining species coexistence patterns is a major challenge in ecology. The
      zonation occurring along elevation gradients, or at bioclimatic contact zones,
      offers a good opportunity to improve such understanding because the small scale
      at which the partitioning occurs facilitates inference based on experiments and
      ecological modelling. We studied the influence of abiotic gradients, habitat
      types, and interspecific competition in determining the spatial turnover between
      two pipit and two bunting species in NW Spain. We explored two independent lines
      of evidence to draw inference about the relative importance of environment and
      biotic interactions in driving range partitioning along elevation, latitude, and
      longitude. We combined occurrence data with environmental data to develop joint
      species distribution models (JSDM), in order to attribute co-occurrence (or
      exclusion) to shared (or divergent) environmental responses and to interactions
      (attraction or exclusion). In the same region, we tested for interference
      competition by means of playback experiments in the contact zone. The JSDMs
      highlighted different responses for the two species pairs, although we did not
      find direct evidence of interspecific aggressiveness in our playback experiments.
      In pipits, partitioning was explained by divergent climate and habitat
      requirements and also by the negative correlations between species not explained
      by the environment. This significant residual correlation may reflect forms of
      competition others than direct interference, although we could not completely
      exclude the influence of unmeasured environmental predictors. When bunting
      species co-occurred, it was because of shared habitat preferences, and a possible
      limitation to dispersal might cause their partitioning. Our results indicate that
      no single mechanism dominates in driving the distribution of our study species,
      but rather distributions are determined by the combination of many small forces
      including biotic and abiotic determinants of niche, whose relative strengths
      varied among species.

PMID- 28428858
TI  - Genetic diversity and spatial structure of the Rufous-throated Antbird
      (Gymnopithys rufigula), an Amazonian obligate army-ant follower.
AB  - Amazonian understory antbirds are thought to be relatively sedentary and to have
      limited dispersal ability; they avoid crossing forest gaps, and even narrow roads
      through a forest may limit their territories. However, most evidence for
      sedentariness in antbirds comes from field observations and plot-based recapture
      of adult individuals, which do not provide evidence for lack of genetic
      dispersal, as this often occurs through juveniles. In this study, we used
      microsatellite markers and mitochondrial control-region sequences to investigate
      contemporary and infer historical patterns of genetic diversity and structure of
      the Rufous-throated Antbird (Gymnopithys rufigula) within and between two large
      reserves in central Amazonia. Analyses based on microsatellites suggested two
      genetically distinct populations and asymmetrical gene flow between them. Within
      a population, we found a lack of genetic spatial autocorrelation, suggesting that
      genotypes are randomly distributed and that G. rufigula may disperse longer
      distances than expected for antbirds. Analyses based on mitochondrial sequences
      did not recover two clear genetic clusters corresponding to the two reserves and
      indicated the whole population of the Rufous-throated Antbird in the region has
      been expanding over the last 50,000 years. Historical migration rates were low
      and symmetrical between the two reserves, but we found evidence for a recent
      unilateral increase in gene flow. Recent differentiation between individuals of
      the two reserves and a unilateral increase in gene flow suggest that recent urban
      expansion and habitat loss may be driving changes and threatening populations of
      Rufous-throated Antbird in central Amazonia. As ecological traits and behavioral
      characteristics affect patterns of gene flow, comparative studies of other
      species with different behavior and ecological requirements will be necessary to
      better understand patterns of genetic dispersal and effects of urban expansion on
      Amazonian understory antbirds.

PMID- 28428860
TI  - Complex trait relationships between leaves and absorptive roots: Coordination in
      tissue N concentration but divergence in morphology.
AB  - Leaves and absorptive roots (i.e., first-order root) are above- and belowground
      plant organs related to resource acquisition; however, it is controversy over
      whether these two sets of functional traits vary in a coordinated manner. Here,
      we examined the relationships between analogous above- and belowground traits,
      including chemical (tissue C and N concentrations) and morphological traits
      (thickness and diameter, specific leaf area and root length, and tissue density)
      of 154 species sampling from eight subtropical and temperate forests. Our results
      showed that N concentrations of leaves and absorptive roots were positively
      correlated independent of phylogeny and plant growth forms, whereas morphological
      traits between above- and belowground organs varied independently. These results
      indicate that, different from plant economics spectrum theory, there is a complex
      integration of diverse adaptive strategies of plant species to above- and
      belowground environments, with convergent adaptation in nutrient traits but
      divergence in morphological traits across plant organs. Our results offer a new
      perspective for understanding the resource capture strategies of plants in
      adaptation to heterogeneous environments, and stress the importance of
      phylogenetic consideration in the discussion of cross-species trait
      relationships.

PMID- 28428861
TI  - Does the morphological fit between flowers and pollinators affect pollen
      deposition? An experimental test in a buzz-pollinated species with anther
      dimorphism.
AB  - Some pollination systems, such as buzz-pollination, are associated with floral
      morphologies that require a close physical interaction between floral sexual
      organs and insect visitors. In these systems, a pollinator's size relative to the
      flower may be an important feature determining whether the visitor touches both
      male and female sexual organs and thus transfers pollen between plants
      efficiently. To date, few studies have addressed whether in fact the "fit"
      between flower and pollinator influences pollen transfer, particularly among buzz
      pollinated species. Here we use Solanum rostratum, a buzz-pollinated plant with
      dimorphic anthers and mirror-image flowers, to investigate whether the
      morphological fit between the pollinator's body and floral morphology influences
      pollen deposition. We hypothesized that when the size of the pollinator matches
      the separation between the sexual organs in a flower, more pollen should be
      transferred to the stigma than when the visitor is either too small or too big
      relative to the flower. To test this hypothesis, we exposed flowers of S.
      rostratum with varying levels of separation between sexual organs, to bumblebees
      (Bombus terrestris) of different sizes. We recorded the number of visits
      received, pollen deposition, and fruit and seed production. We found higher
      pollen deposition when bees were the same size or bigger than the separation
      between anther and stigma within a flower. We found a similar, but not
      statistically significant pattern for fruit set. In contrast, seed set was more
      likely to occur when the size of the flower exceeded the size of the bee,
      suggesting that other postpollination processes may be important in translating
      pollen receipt to seed set. Our results suggest that the fit between flower and
      pollinator significantly influences pollen deposition in this buzz-pollinated
      species. We speculate that in buzz-pollinated species where floral morphology and
      pollinators interact closely, variation in the visitor's size may determine
      whether it acts mainly as a pollinator or as a pollen thief (i.e., removing
      pollen rewards but contributing little to pollen deposition and fertilization).

PMID- 28428862
TI  - Environmental heterogeneity does not affect levels of phenotypic plasticity in
      natural populations of three Drosophila species.
AB  - Adaptation of natural populations to variable environmental conditions may occur
      by changes in trait means and/or in the levels of plasticity. Theory predicts
      that environmental heterogeneity favors plasticity of adaptive traits. Here we
      investigated the performance in several traits of three sympatric Drosophila
      species freshly collected in two environments that differ in the heterogeneity of
      environmental conditions. Differences in trait means within species were found in
      several traits, indicating that populations differed in their evolutionary
      response to the environmental conditions of their origin. Different species
      showed distinct adaptation with a very different role of plasticity across
      species for coping with environmental changes. However, geographically distinct
      populations of the same species generally displayed the same levels of plasticity
      as induced by fluctuating thermal regimes. This indicates a weak and trait
      specific effect of environmental heterogeneity on plasticity. Furthermore,
      similar levels of plasticity were found in a laboratory-adapted population of
      Drosophila melanogaster with a common geographic origin but adapted to the
      laboratory conditions for more than 100 generations. Thus, this study does not
      confirm theoretical predictions on the degree of adaptive plasticity among
      populations in relation to environmental heterogeneity but shows a very distinct
      role of species-specific plasticity.

PMID- 28428863
TI  - Switching among natal and auxiliary hosts increases vulnerability of Spodoptera
      exigua (Hubner) (Lepidoptera: Noctuidae) to insecticides.
AB  - The role of insecticidal application and host plant resistance in managing
      Spodoptera exigua has been well documented, but the effect of different host
      plants, on which the pest cycles its population in the field, has seldom been
      investigated. Therefore, we have studied the vulnerability of S. exigua against
      commonly used insecticides (cypermethrin, chlorpyrifos, lufenuron, and emamectin
      benzoate) with different mode of actions when it switches its generations from
      natal to auxiliary hosts and vice versa. Different field populations being
      established on different host plants including castor, cauliflower, cotton, okra,
      and spinach were collected and reared in the laboratory before insecticidal
      bioassays. The role of larval diet and host plant switching on their response to
      tolerate applied insecticides was studied using leaf-dip bioassay methods. Host
      switching demonstrated a significant role in altering the vulnerability of S.
      exigua populations to tested insecticides. Spodoptera exigua sourced from castor,
      when switched host to okra and spinach, exhibited 50% higher mortality when
      treated with emamectin benzoate. This trend in mortality was consistent upon
      complete host switch cycle (natal-auxiliary-natal host). However, the highest
      increase (92%) in vulnerability was recorded when the larvae were shifted to
      spinach from cotton. In general, chlorpyrifos and lufenuron had highest
      efficacies in terms of larval mortality. The findings of present studies provide
      insights to a better understanding the behavior of polyphagous pests and the role
      of different host plants in altering the susceptibility of these pests against
      applied insecticides. Ultimately the results warrant that due consideration
      should be given to cropping patterns and time of host switching by pest
      population during planning and executing chemical control.

PMID- 28428864
TI  - Integrating biogeography, threat and evolutionary data to explore extinction
      crisis in the taxonomic group of cycads.
AB  - Will the ongoing extinction crisis cause a severe loss of evolutionary
      information accumulated over millions of years on the tree of life? This question
      has been largely explored, particularly for vertebrates and angiosperms. However,
      no equivalent effort has been devoted to gymnosperms. Here, we address this
      question focusing on cycads, the gymnosperm group exhibiting the highest
      proportion of threatened species in the plant kingdom. We assembled the first
      complete phylogeny of cycads and assessed how species loss under three scenarios
      would impact the cycad tree of life. These scenarios are as follows: (1) All top
      50% of evolutionarily distinct (ED) species are lost; (2) all threatened species
      are lost; and (3) only all threatened species in each IUCN category are lost.
      Finally, we analyzed the biogeographical pattern of cycad diversity hotspots and
      tested for gaps in the current global conservation network. First, we showed that
      threatened species are not significantly clustered on the cycad tree of life.
      Second, we showed that the loss of all vulnerable or endangered species does not
      depart significantly from random loss. In contrast, the loss of all top 50% ED,
      all threatened or all critically endangered species, would result in a greater
      loss of PD (Phylogenetic Diversity) than expected. To inform conservation
      decisions, we defined five hotpots of diversity, and depending on the diversity
      metric used, these hotspots are located in Southern Africa, Australia, Indo
      Pacific, and Mexico and all are found within protected areas. We conclude that
      the phylogenetic diversity accumulated over millions of years in the cycad tree
      of life would not survive the current extinction crisis. As such, prioritizing
      efforts based on ED and concentrating efforts on critically endangered species
      particularly in southern Africa, Australia, Indo-Pacific, and Mexico are required
      to safeguarding the evolutionary diversity in the cycad tree of life.

PMID- 28428865
TI  - Competition and facilitation structure plant communities under nurse tree
      canopies in extremely stressful environments.
AB  - Nurse plant facilitation in stressful environments can produce an environment
      with relatively low stress under its canopy. These nurse plants may produce the
      conditions promoting intense competition between coexisting species under the
      canopy, and canopies may establish stress gradients, where stress increases
      toward the edge of the canopy. Competition and facilitation on these stress
      gradients may control species distributions in the communities under canopies. We
      tested the following predictions: (1) interactions between understory species
      shift from competition to facilitation in habitats experiencing increasing stress
      from the center to the edge of canopy of a nurse plant, and (2) species
      distributions in understory communities are controlled by competitive
      interactions at the center of canopy, and facilitation at the edge of the canopy.
      We tested these predictions using a neighbor removal experiment under nurse trees
      growing in arid environments. Established individuals of each of four of the most
      common herbaceous species in the understory were used in the experiment. Two
      species were more frequent in the center of the canopy, and two species were more
      frequent at the edge of the canopy. Established individuals of each species were
      subjected to neighbor removal or control treatments in both canopy center and
      edge habitats. We found a shift from competitive to facilitative interactions
      from the center to the edge of the canopy. The shift in the effect of neighbors
      on the target species can help to explain species distributions in these
      canopies. Canopy-dominant species only perform well in the presence of neighbors
      in the edge microhabitat. Competition from canopy-dominant species can also limit
      the performance of edge-dominant species in the canopy microhabitat. The shift
      from competition to facilitation under nurse plant canopies can structure the
      understory communities in extremely stressful environments.

PMID- 28428866
TI  - Capture efficiency and trophic adaptations of a specialist and generalist
      predator: A comparison.
AB  - Specialist true predators are expected to exhibit higher capture efficiencies for
      the capture of larger and dangerous prey than generalist predators due to their
      possession of specialized morphological and behavioral adaptations. We used an
      araneophagous spider (Lampona murina) and a generalist spider (Drassodes
      lapidosus) as phylogenetically related model species and investigated their
      realized and fundamental trophic niches and their efficacy with respect to prey
      capture and prey handling. The trophic niche of both species confirmed that
      Lampona had a narrow trophic niche with a predominance of spider prey (including
      conspecifics), while the niche of Drassodes was wide, without any preference. DNA
      analysis of the gut contents of Lampona spiders collected in the field revealed
      that spiders form a significant part of its natural diet. Lampona captured
      significantly larger prey than itself and the prey captured by Drassodes. As
      concerns hunting strategy, Lampona grasped the prey with two pairs of legs
      possessing scopulae, whereas Drassodes immobilized prey with silk. Lampona
      possess forelegs equipped with scopulae and a thicker cuticle similar to other
      nonrelated araneophagous spiders. Lampona fed for a longer time and extracted
      more nutrients than Drassodes. We show that specialized behavioral and
      morphological adaptations altogether increase the hunting efficiency of
      specialists when compared to generalists.

PMID- 28428867
TI  - Adaptative evolution of the Vkorc1 gene in Mus musculus domesticus is influenced
      by the selective pressure of anticoagulant rodenticides.
AB  - Anticoagulant rodenticides are commonly used to control rodent pests worldwide.
      They specifically inhibit the vitamin K epoxide reductase (VKORC1), which is an
      enzyme encoded by the Vkorc1 gene, involved in the recycling of vitamin K.
      Therefore, they prevent blood clotting. Numerous mutations of Vkorc1 gene were
      reported in rodents, and some are involved in the resistant to rodenticides
      phenotype. Two hundred and sixty-six mice tails were received from 65 different
      locations in France. Coding sequences of Vkorc1 gene were sequenced in order to
      detect mutations. Consequences of the observed mutations were evaluated by the
      use of recombinant VKORC1. More than 70% of mice presented Vkorc1 mutations.
      Among these mice, 80% were homozygous. Contrary to brown rats for which only one
      predominant Vkorc1 genotype was found in France, nine missense single mutations
      and four double mutations were observed in house mice. The single mutations lead
      to resistance to first-generation antivitamin K (AVKs) only and are certainly
      associated with the use of these first-generation molecules by nonprofessionals
      for the control of mice populations. The double mutations, probably obtained by
      genetic recombination, lead to in vitro resistance to all AVKs. They must be
      regarded as an adaptive evolution to the current use of second-generation AVKs.
      The intensive use of first-generation anticoagulants probably allowed the
      selection of a high diversity of mutations, which makes possible the genetic
      recombination and consequently provokes the emergence of the more resistant
      mutated Vkorc1 described to date.

PMID- 28428868
TI  - Metapopulation patterns of additive and nonadditive genetic variance in the sea
      bass (Dicentrarchus labrax).
AB  - Describing and explaining the geographic within-species variation in phenotypes
      ("phenogeography") in the sea over a species distribution range is central to our
      understanding of a variety of eco-evolutionary topics. However, phenogeographic
      studies that have a large potential to investigate adaptive variation are
      overcome by phylogeographic studies, still mainly focusing on neutral markers.
      How genotypic and phenotypic data could covary over large geographic scales
      remains poorly understood in marine species. We crossed 75 noninbred sires (five
      origins) and 26 dams (two origins; each side of a hybrid zone) in a factorial
      diallel cross in order to investigate geographic variation for early survival and
      sex ratio in the metapopulation of the European sea bass (Dicentrarchus labrax),
      a highly prized marine fish species. Full-sib families (N = 1,950) were produced
      and reared in a common environment. Parentage assignment of 7,200 individuals was
      performed with seven microsatellite markers. Generalized linear models showed
      significant additive effects for both traits and pleiotropy between traits. A
      significant nonadditive genetic effect was detected. Different expression of
      traits and distinct relative performances were found for reciprocal crosses
      involving populations located on each side of the main hybrid zone located at the
      Almeria-Oran front, illustrating asymmetric reproductive isolation. The poor
      fitness performance observed for the Western Mediterranean population of sea bass
      is discussed as it represents the main source of seed hatchery production, but
      also because it potentially illustrates nonadaptive introgression and
      maladaptation.

PMID- 28428869
TI  - Rapid maximum likelihood ancestral state reconstruction of continuous characters:
      A rerooting-free algorithm.
AB  - Ancestral state reconstruction is a method used to study the evolutionary
      trajectories of quantitative characters on phylogenies. Although efficient
      methods for univariate ancestral state reconstruction under a Brownian motion
      model have been described for at least 25 years, to date no generalization has
      been described to allow more complex evolutionary models, such as multivariate
      trait evolution, non-Brownian models, missing data, and within-species variation.
      Furthermore, even for simple univariate Brownian motion models, most phylogenetic
      comparative R packages compute ancestral states via inefficient tree rerooting
      and full tree traversals at each tree node, making ancestral state reconstruction
      extremely time-consuming for large phylogenies. Here, a computationally efficient
      method for fast maximum likelihood ancestral state reconstruction of continuous
      characters is described. The algorithm has linear complexity relative to the
      number of species and outperforms the fastest existing R implementations by
      several orders of magnitude. The described algorithm is capable of performing
      ancestral state reconstruction on a 1,000,000-species phylogeny in fewer than 2 s
      using a standard laptop, whereas the next fastest R implementation would take
      several days to complete. The method is generalizable to more complex
      evolutionary models, such as phylogenetic regression, within-species variation,
      non-Brownian evolutionary models, and multivariate trait evolution. Because this
      method enables fast repeated computations on phylogenies of virtually any size,
      implementation of the described algorithm can drastically alleviate the
      computational burden of many otherwise prohibitively time-consuming tasks
      requiring reconstruction of ancestral states, such as phylogenetic imputation of
      missing data, bootstrapping procedures, Expectation-Maximization algorithms, and
      Bayesian estimation. The described ancestral state reconstruction algorithm is
      implemented in the Rphylopars functions anc.recon and phylopars.

PMID- 28428870
TI  - Gene expression profiling during the embryo-to-larva transition in the giant red
      sea urchin Mesocentrotus franciscanus.
AB  - In echinoderms, major morphological transitions during early development are
      attributed to different genetic interactions and changes in global expression
      patterns that shape the regulatory program for the specification of embryonic
      territories. In order more thoroughly to understand these biological and
      molecular processes, we examined the transcriptome structure and expression
      profiles during the embryo-to-larva transition of a keystone species, the giant
      red sea urchin Mesocentrotus franciscanus. Using a de novo assembly approach, we
      obtained 176,885 transcripts from which 60,439 (34%) had significant alignments
      to known proteins. From these transcripts, ~80% were functionally annotated
      allowing the identification of ~2,600 functional, structural, and regulatory
      genes involved in developmental process. Analysis of expression profiles between
      gastrula and pluteus stages of M. franciscanus revealed 791 differentially
      expressed genes with 251 GO overrepresented terms. For gastrula, up-regulated GO
      terms were mainly linked to cell differentiation and signal transduction involved
      in cell cycle checkpoints. In the pluteus stage, major GO terms were associated
      with phosphoprotein phosphatase activity, muscle contraction, and olfactory
      behavior, among others. Our evolutionary comparative analysis revealed that
      several of these genes and functional pathways are highly conserved among
      echinoids, holothuroids, and ophiuroids.

PMID- 28428871
TI  - Does wintering north or south of the Sahara correlate with timing and breeding
      performance in black-tailed godwits?
AB  - Migrating long distances requires time and energy, and may interact with an
      individual's performance during breeding. These seasonal interactions in
      migratory animals are best described in populations with disjunct nonbreeding
      distributions. The black-tailed godwit (Limosa limosa limosa), which breeds in
      agricultural grasslands in Western Europe, has such a disjunct nonbreeding
      distribution: The majority spend the nonbreeding season in West Africa, while a
      growing number winters north of the Sahara on the Iberian Peninsula. To test
      whether crossing the Sahara has an effect on breeding season phenology and
      reproductive parameters, we examined differences in the timing of arrival,
      breeding habitat quality, lay date, egg volume, and daily nest survival among
      godwits (154 females and 157 males), individually marked in a breeding area in
      the Netherlands for which wintering destination was known on the basis of
      resightings. We also examined whether individual repeatability in arrival date
      differed between birds wintering north or south of the Sahara. Contrary to
      expectation, godwits wintering south of the Sahara arrived two days earlier and
      initiated their clutch six days earlier than godwits wintering north of the
      Sahara. Arrival date was equally repeatable for both groups, and egg volume
      larger in birds wintering north of the Sahara. Despite these differences, we
      found no association between wintering location and the quality of breeding
      habitat or nest survival. This suggests that the crossing of an important
      ecological barrier and doubling of the migration distance, twice a year, do not
      have clear negative reproductive consequences for some long-distance migrants.

PMID- 28428872
TI  - Are whooping cranes destined for extinction? Climate change imperils recruitment
      and population growth.
AB  - Identifying climatic drivers of an animal population's vital rates and locating
      where they operate steers conservation efforts to optimize species recovery. The
      population growth of endangered whooping cranes (Grus americana) hinges on
      juvenile recruitment. Therefore, we identify climatic drivers (solar activity
      [sunspots] and weather) of whooping crane recruitment throughout the species'
      life cycle (breeding, migration, wintering). Our method uses a repeated cross
      validated absolute shrinkage and selection operator approach to identify drivers
      of recruitment. We model effects of climate change on those drivers to predict
      whooping crane population growth given alternative scenarios of climate change
      and solar activity. Years with fewer sunspots indicated greater recruitment.
      Increased precipitation during autumn migration signified less recruitment. On
      the breeding grounds, fewer days below freezing during winter and more
      precipitation during breeding suggested less recruitment. We predicted whooping
      crane recruitment and population growth may fall below long-term averages during
      all solar cycles when atmospheric CO2 concentration increases, as expected, to
      500 ppm by 2050. Species recovery during a typical solar cycle with 500 ppm may
      require eight times longer than conditions without climate change and the chance
      of population decline increases to 31%. Although this whooping crane population
      is growing and may appear secure, long-term threats imposed by climate change and
      increased solar activity may jeopardize its persistence. Weather on the breeding
      grounds likely affects recruitment through hydrological processes and predation
      risk, whereas precipitation during autumn migration may influence juvenile
      mortality. Mitigating threats or abating climate change should occur within ~30
      years or this wild population of whooping cranes may begin declining.

PMID- 28428873
TI  - A maize landrace that emits defense volatiles in response to herbivore eggs
      possesses a strongly inducible terpene synthase gene.
AB  - Maize (Zea mays) emits volatile terpenes in response to insect feeding and egg
      deposition to defend itself against harmful pests. However, maize cultivars
      differ strongly in their ability to produce the defense signal. To further
      understand the agroecological role and underlying genetic mechanisms for
      variation in terpene emission among maize cultivars, we studied the production of
      an important signaling component (E)-caryophyllene in a South American maize
      landrace Braz1006 possessing stemborer Chilo partellus egg inducible defense
      trait, in comparison with the European maize line Delprim and North American
      inbred line B73. The (E)-caryophyllene production level and transcript abundance
      of TPS23, terpene synthase responsible for (E)-caryophyllene formation, were
      compared between Braz1006, Delprim, and B73 after mimicked herbivory. Braz1006
      TPS23 was heterologously expressed in E. coli, and amino acid sequences were
      determined. Furthermore, electrophysiological and behavioral responses of a key
      parasitic wasp Cotesia sesamiae to C. partellus egg-induced Braz1006 volatiles
      were determined using coupled gas chromatography electroantennography and
      olfactometer bioassay studies. After elicitor treatment, Braz1006 released
      eightfold higher (E)-caryophyllene than Delprim, whereas no (E)-caryophyllene was
      detected in B73. The superior (E)-caryophyllene production by Braz1006 was
      positively correlated with high transcript levels of TPS23 in the landrace
      compared to Delprim. TPS23 alleles from Braz1006 showed dissimilarities at
      different sequence positions with Delprim and B73 and encodes an active enzyme.
      Cotesia sesamiae was attracted to egg-induced volatiles from Braz1006 and
      synthetic (E)-caryophyllene. The variation in (E)-caryophyllene emission between
      Braz1006 and Delprim is positively correlated with induced levels of TPS23
      transcripts. The enhanced TPS23 activity and corresponding (E)-caryophyllene
      production by the maize landrace could be attributed to the differences in amino
      acid sequence with the other maize lines. This study suggested that the same
      analogous genes could have contrasting expression patterns in different maize
      genetic backgrounds. The current findings provide valuable insight not only into
      genetic mechanisms underlying variation in defense signal production but also the
      prospect of introgressing the novel defense traits into elite maize varieties for
      effective and ecologically sound protection of crops against damaging insect
      pests.

PMID- 28428874
TI  - Population assessment using multivariate time-series analysis: A case study of
      rockfishes in Puget Sound.
AB  - Estimating a population's growth rate and year-to-year variance is a key
      component of population viability analysis (PVA). However, standard PVA methods
      require time series of counts obtained using consistent survey methods over many
      years. In addition, it can be difficult to separate observation and process
      variance, which is critical for PVA. Time-series analysis performed with
      multivariate autoregressive state-space (MARSS) models is a flexible statistical
      framework that allows one to address many of these limitations. MARSS models
      allow one to combine surveys with different gears and across different sites for
      estimation of PVA parameters, and to implement replication, which reduces the
      variance-separation problem and maximizes informational input for mean trend
      estimation. Even data that are fragmented with unknown error levels can be
      accommodated. We present a practical case study that illustrates MARSS analysis
      steps: data choice, model set-up, model selection, and parameter estimation. Our
      case study is an analysis of the long-term trends of rockfish in Puget Sound,
      Washington, based on citizen science scuba surveys, a fishery-independent trawl
      survey, and recreational fishery surveys affected by bag-limit reductions. The
      best-supported models indicated that the recreational and trawl surveys tracked
      different, temporally independent assemblages that declined at similar rates (an
      average of -3.8% to -3.9% per year). The scuba survey tracked a separate
      increasing and temporally independent assemblage (an average of 4.1% per year).
      Three rockfishes (bocaccio, canary, and yelloweye) are listed in Puget Sound
      under the US Endangered Species Act (ESA). These species are associated with deep
      water, which the recreational and trawl surveys sample better than the scuba
      survey. All three ESA-listed rockfishes declined as a proportion of recreational
      catch between the 1970s and 2010s, suggesting that they experienced similar or
      more severe reductions in abundance than the 3.8-3.9% per year declines that were
      estimated for rockfish populations sampled by the recreational and trawl surveys.

PMID- 28428875
TI  - Genetic relationships among Eriobotrya species revealed by genome-wide RAD
      sequence data.
AB  - Restriction site-associated DNA sequencing (RAD-seq) was used to illuminate the
      genetic relationships among Eriobotrya species. The raw data were filtered, and
      221 million clean reads were used for further analysis. A total of 1,983,332 SNPs
      were obtained from 23 Eriobotrya species and two relative genera. We obtained
      similar results by neighbor-joining and maximum likelihood phylogenetic trees.
      All Eriobotrya plants grouped together into a big clade, and two out-groups
      clustered together into a single or separate clade. Chinese and Vietnam
      accessions were distributed throughout the dendrogram. There was nonsignificant
      correlation between genotype and geographical distance. However, clustering
      results were correlated with leaf size to some extent. The Eriobotrya species
      could be divided into following three groups based on leaf size and phylogenetic
      analysis: group A and group B comprised of small leaves with <10 cm length except
      E. stipularis (16.76 cm), and group C can be further divided into two subgroups,
      which contained medium-size leaves with a leaf length ranged from 10 to 20 cm and
      a leaf length bigger than 20 cm.

PMID- 28428876
TI  - Staphylococcus aureus infections following knee and hip prosthesis insertion
      procedures.
AB  - BACKGROUND: Staphylococcus aureus is the most common and most important pathogen
      following knee and hip arthroplasty procedures. Understanding the epidemiology of
      invasive S. aureus infections is important to quantify this serious complication.
      METHODS: This nested retrospective cohort analysis included adult patients who
      had undergone insertion of knee or hip prostheses with clean or clean
      contaminated wound class at 11 hospitals between 2003-2006. Invasive S. aureus
      infections, non-superficial incisional surgical site infections (SSIs) and blood
      stream infections (BSIs), were prospectively identified following each procedure.
      Prevalence rates, per 100 procedures, were estimated. RESULTS: 13,719 prosthetic
      knee (62%) and hip (38%) insertion procedures were performed. Of 92 invasive S.
      aureus infections identified, SSIs were more common (80%) than SSI and BSI (10%)
      or BSI alone (10%). The rate of invasive S. aureus infection/100 procedures was
      0.57 [95% CI: 0.43-0.73] for knee insertion and 0.83 [95% CI: 0.61-1.08] for hip
      insertion. More than half (53%) were methicillin-resistant. Median time-to-onset
      of infection was 34 and 26 days for knee and hip insertion, respectively.
      Infection was associated with higher National Healthcare Safety Network risk
      index (p <= 0.0001). CONCLUSIONS: Post-operative invasive S. aureus infections
      were rare, but difficult-to-treat methicillin-resistant infections were
      relatively common. Optimizing preventative efforts may greatly reduce the
      healthcare burden associated with S. aureus infections.

PMID- 28428877
TI  - P. aeruginosa colonization at ICU admission as a risk factor for developing P.
      aeruginosa ICU pneumonia.
AB  - OBJECTIVE: To determine the incidence of P. aeruginosa (PA) ICU pneumonia and its
      independent association with PA colonization at ICU admission. METHODS: This was
      a post-hoc analysis of a prospectively collected cohort study. Adult ICU patients
      with a length of stay of >=48 h were included and assessed for microbiologically
      confirmed PA ICU pneumonia. Multivariate survival analysis was performed,
      including the covariates age, gender, PA colonization at ICU admission, ICU
      admission specialty and mechanical ventilation at ICU admission, while taking
      into account the effect of competing risks. RESULTS: We included 5093 patients,
      2447 (48%) were tested for colonization; of those 226 (9.2%) were PA colonized at
      ICU admission. The incidence of PA ICU pneumonia was 1.34% (n = 68). PA
      colonization was an independent risk factor (subdistribution hazard ratio [SHR]
      8.8; 95% confidence interval [CI] 4.9-15.7), as was mechanical ventilation (SHR
      5.3, 95% CI 2.7-10.6). CONCLUSION: In this study the incidence of P. aeruginosa
      ICU pneumonia was 1.34%. Hazard ratios for PA colonized patients compared to non
      colonized to develop PA ICU pneumonia were 8.8. The high risk associated with P.
      aeruginosa colonization for subsequent infection may offer a target for future
      interventions.

PMID- 28428878
TI  - Immunization dropout rate and data quality among children 12-23 months of age in
      Ghana.
AB  - BACKGROUND: Immunization against diseases is one of the most important public
      health interventions with cost effective means to preventing childhood morbidity,
      mortality and disability. However, a proportion of children particularly in
      Africa are not fully immunized with the recommended vaccines. Thus, many children
      are still susceptible to the Expanded Program on Immunization (EPI) targeted
      diseases. The objective of this study was to determine the immunization dropout
      rate and data quality among children aged 12-23 months in Techiman Municipality,
      Ghana. METHODS: A cross-sectional cluster survey was conducted among 600
      children. Data was collected using semi-structured questionnaire through face-to
      face interviews. Before the main data collection, the tools were pre-tested in
      three different communities in the Municipality. The mothers/caregivers were
      interviewed, extracted information from the child immunization cards and
      observation employed to confirm the presence of Bacillus Calmette-Guerin (BCG)
      scar on each child. Routine immunization data was also extracted from
      immunization registers and annual reports in the Municipality. RESULTS:
      Immunization coverage for each of the fifteen vaccines doses is above 90.0% while
      full childhood immunized status is 89.5%. Immunization dropout rate was 5.6%
      (using BCG and Measles as proxy vaccines). This is lower than the 10.0% cutoff
      point by World Health Organization. However, routine administrative data was
      characterized by some discrepancies (e.g. > 100.0% immunization coverage for each
      of the vaccines) and high dropout rate (BCG - Measles = 31.5%). Binary regression
      was performed to determine predictors of dropout rate. The following were
      statistically significant: married (OR = 0.31; 95% = CI 0.15-0.62; and p =
      0.001), Christianity (OR = 0.27; 95% CI = 0.13-0.91; and p < 0.001), female child
      (OR = 0.50; 95% CI = 0.26-0.91; and p = 0.024) and possession of immunization
      card (OR = 50.3; 95% CI = 14.40-175.92; and p < 0.001) were found to be
      associated with immunization dropout. CONCLUSION: Childhood full immunized status
      (89.5%) and immunization coverages (>90%) are high while dropout rate is lower
      than the recommended cutoff point by WHO. However, immunization data quality
      remains inadequate. Thus, health education and orientation of service providers
      is urgently needed. In addition, immunization registers and data quality are
      issues that require attention.

PMID- 28428879
TI  - A systems biology approach to investigating the influence of exercise and fitness
      on the composition of leukocytes in peripheral blood.
AB  - BACKGROUND: Exercise immunology has become a growing field in the past 20 years,
      with an emphasis on understanding how different forms of exercise affect immune
      function. Mechanistic studies are beginning to shed light on how exercise may
      impair the development of cancer or be used to augment cancer treatment. The
      beneficial effects of exercise on the immune system may be exploited to improve
      patient responses to cancer immunotherapy. METHODS: We investigated the effects
      of acute exercise on the composition of peripheral blood leukocytes over time in
      a male population of varying fitness. Subjects performed a brief maximal
      intensity cycling regimen and a longer less intense cycling regimen at separate
      visits. Leukocytes were measured by multi-parameter flow cytometry of more than
      50 immunophenotypes for each collection sample. RESULTS: We found a differential
      induction of leukocytosis dependent on exercise intensity and duration. Cytotoxic
      natural killer cells demonstrated the greatest increase (average of 5.6 fold)
      immediately post-maximal exercise whereas CD15+ granulocytes demonstrated the
      largest increase at 3 h post-maximal exercise (1.6 fold). The longer, less
      intense endurance exercise resulted in an attenuated leukocytosis. Induction of
      leukocytosis did not differ in our limited study of active (n = 10) and sedentary
      (n = 5) subjects to exercise although we found that in baseline samples,
      sedentary individuals had elevated percentages of CD45RO+ memory CD4+ T cells and
      elevated proportions of CD4+ T cells expressing the negative immune regulator
      programmed death-1 (PD-1). Finally, we identified several leukocytes whose
      presence correlated with obesity related fitness parameters. CONCLUSIONS: Our
      data suggests that leukocytes subsets are differentially mobilized into the
      peripheral blood and dependent on the intensity and duration of exercise. Pre
      existing compositional differences of leukocytes were associated with various
      fitness parameters.

PMID- 28428880
TI  - Long-term complete remission with Ipilimumab in metastatic castrate-resistant
      prostate cancer: case report of two patients.
AB  - BACKGROUND: Prostate cancer is one of the most common cancers in men and the
      fourth leading cause of cancer mortality worldwide. Although major progress has
      been achieved in the last years for patients with metastatic castrate-resistant
      prostate cancer (mCRPC), thanks to next-generation androgen receptor axis
      targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been
      widely approved and used for the treatment of prostate cancer. Two large studies
      with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody
      reported improved progression-free survival, but not statistically improved
      overall survival at the primary analysis (CA184 043 and CA184 095). CASE
      PRESENTATION: Here, we report on two patients who received ipilimumab in these
      trials and are still in long-term complete remission with a follow-up of 64 and
      52 months respectively after the initiation of ipilimumab. Immunohistochemical
      staining for hMLH1, hMSH2, hMSH6 and PMS2 was performed on archival prostate
      biopsy samples from one of the two patients; they exhibited normal protein
      expression. Interestingly for this patient, a high CD3+ and CD8+ T cell
      infiltration was observed on archival prostate biopsies as well as Treg FoxP3+ T
      cells. CONCLUSION: Ipilimumab produces clinical activity in patients with CRPC,
      including very long responders with no detectable residual disease.

PMID- 28428881
TI  - Nano-Pulse Stimulation is a physical modality that can trigger immunogenic tumor
      cell death.
AB  - BACKGROUND: We have been developing a non-thermal, drug-free tumor therapy called
      Nano-Pulse Stimulation (NPS) that delivers ultrashort electric pulses to tumor
      cells which eliminates the tumor and inhibits secondary tumor growth. We
      hypothesized that the mechanism for inhibiting secondary tumor growth involves
      stimulating an adaptive immune response via an immunogenic form of apoptosis,
      commonly known as immunogenic cell death (ICD). ICD is characterized by the
      emission of danger-associated molecular patterns (DAMPs) that serve to recruit
      immune cells to the site of the tumor. Here we present evidence that NPS
      stimulates both caspase 3/7 activation indicative of apoptosis, as well as the
      emission of three critical DAMPs: ecto-calreticulin (CRT), ATP and HMGB1.
      METHODS: After treating three separate cancer cell lines (MCA205, McA-RH7777,
      Jurkat E6-1) with NPS, cells were incubated at 37  degrees C. Cell-culture
      supernatants were collected after three-hours to measure for activated caspases
      3/7 and after 24 h to measure CRT, ATP and HMGB1 levels. We measured the changes
      in caspase-3 activation with Caspase-Glo(r) by Promega, ecto-CRT with anti-CRT
      antibody and flow cytometry, ATP by luciferase light generation and HMGB1 by
      ELISA. RESULTS: The initiation of apoptosis in cultured cells is greatest at 15
      kV/cm and requires 50 A/cm2. Reducing this current inhibits cell death. Activated
      caspase-3 increases 8-fold in Jurkat E6-1 cells and 40% in rat hepatocellular
      carcinoma and mouse fibrosarcoma cells by 3 h post treatment. This increase is
      non-linear and peaks at 15-20 J/mL for all field strengths. 10 and 30 kV/cm
      fields exhibited the lowest response and the 12 and 15 kV/cm fields stimulated
      the largest amount of caspase activation. We measured the three DAMPs 24 h after
      treatment. The expression of cell surface CRT increased in an energy-dependent
      manner in the NPS treated samples. Expression levels reached or exceeded the
      expression levels in the majority of the anthracycline-treated samples at
      energies between 25 and 50 J/mL. Similar to the caspase response at 3 h, secreted
      ATP peaked at 15 J/mL and then rapidly declined at 25 J/mL. HMGB1 release
      increased as treatment energy increased and reached levels comparable to the
      anthracycline-treated groups between 10 and 25 J/mL. CONCLUSION: Nano-Pulse
      Stimulation treatment at specific energies was able to trigger the emission of
      three key DAMPs at levels comparable to Doxorubicin and Mitoxantrone, two known
      inducers of immunogenic cell death (ICD). Therefore NPS is a physical modality
      that can trigger immunogenic cell death in tumor cells.

PMID- 28428882
TI  - Differential phenotypes of memory CD4 and CD8 T cells in the spleen and
      peripheral tissues following immunostimulatory therapy.
AB  - BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or
      murine splenocytes to generate data that is interpreted as representative of
      immune status. Using splenocytes, we have shown memory CD4-T cells that expand
      following systemic immunostimulatory therapies undergo rapid IFNg-mediated
      activation induced cell death (AICD) resulting in a net loss of total CD4-T cells
      which correlates with elevated PD-1 expression. This is in contrast to CD8-T
      cells which expand with minimal PD-1 upregulation and apoptosis. In this study we
      expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and
      distribution in peripheral organs which are more representative of immune
      responses occurring at metastatic sites following immunotherapy. METHODS:
      Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as
      peripheral organs (liver and lungs) in control and immunotherapy treated mice was
      performed to survey the impact of location on memory phenotype and activation
      marker status. Peripheral blood from patients undergoing systemic high dose IL-2
      was also assessed for expression of PD-1 and memory phenotype. RESULTS: Here we
      reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell
      numbers decreased while CD8-T cells expanded at these peripheral sites. In
      contrast to having differential expression of PD-1 as occurs in the spleen, both
      CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver
      and lungs. Further analysis correlated PD-1 expression to CD62Llow (T
      effector/effector memory,TE/EM) expression which are more prevalent in CD4-T
      cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD
      1 expression on TE/EM cells was observed in patients undergoing systemic high
      dose IL-2 therapy. CONCLUSIONS: These data highlight PD-1 expressing and/or TE/EM
      subsets of T cells in circulation as more representative of cells at immune sites
      and underscore the importance of valuation both in lymphoid as well as target
      organs when making determinations about immune status. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01416831. Registered August 12, 2011.

PMID- 28428883
TI  - Response after treatment with pembrolizumab in a patient with myelophthisis due
      to melanoma: the role of checkpoint inhibition in the bone.
AB  - BACKGROUND: Myelophthisis due to melanoma is a rare phenomenon. Treatment
      strategies for patients with this serious complication of malignancy have not
      been well documented, and none have previously reported efficacy of immune
      checkpoint inhibition. Since bone metastases are not measurable lesions per
      standard response criteria, the efficacy of immune checkpoint inhibition in the
      bones is also not well described. CASE PRESENTATION: We describe a patient with
      widespread melanoma metastases involving the bone marrow causing myelophthisis
      and pancytopenia who responded to immune checkpoint inhibition with the anti
      programmed cell death-1 (PD-1) inhibitor pembrolizumab. CONCLUSIONS: This is the
      first report to our knowledge of disease response to immune checkpoint inhibition
      in a patient with myelophthisis. Clinical trials have recently emerged describing
      the efficacy of PD-1 inhibition for disorders regularly involving the bone
      marrow, such as hematologic malignancies, suggesting the importance of better
      understanding the bone marrow as an immunologically active compartment.
      Clinicians should be aware that immune checkpoint inhibition alone may be
      effective in treating malignancy involving the bone marrow, even in cases of
      extensive involvement resulting in pancytopenia due to myelophthisis from a solid
      tumor as our case suggests.

PMID- 28428884
TI  - Phase I clinical trial of combination imatinib and ipilimumab in patients with
      advanced malignancies.
AB  - BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor
      antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4
      blockade and imatinib synergize in mouse models to reduce tumor volume via
      intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined
      with ipilimumab would be tolerable and may synergize in patients with advanced
      cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design)
      was to establish the maximum tolerated dose (MTD) and recommended phase II dose.
      Secondary objectives included evaluation of antitumor activity of the combination
      based on KIT mutation status and the capacity of tumor-associated immune
      biomarkers to predict response. RESULTS: The primary objective to establish the
      maximum tolerated dose (MTD) was achieved, and the recommended phase II doses are
      ipilimumab at 3 mg/kg every 3 weeks and imatinib 400 mg twice daily. Of the 35
      patients treated in the escalation and GIST expansion, none experienced dose
      limiting toxicities. The most common grade 1/2-related adverse events (AEs) were
      fatigue (66%), nausea (57%), anorexia, vomiting (each 31%), edema (29%), and
      anemia, diarrhea, and rash (each 23%). Grade 3 AEs occurred in 6 patients (17%)
      and included fatigue, anemia, fever, rash, and vomiting. There were no grade 4
      AEs. In general, the combination was well tolerated. Among all patients, 2
      responses were seen: 1 partial response (GIST) and 1 partial response (melanoma).
      Stable disease was seen in 6 patients lasting an average of 6 months. The
      melanoma responder was KIT mutated and the GIST responder was wild-type.
      CONCLUSIONS: Our findings suggest that this combination of a targeted agent with
      checkpoint blockade is safe across multiple tumor types. Low activity with no
      clear signal for synergy was observed in escalation or GIST expansion cohorts.
      Assessment of antitumor activity of this combination in the KIT-mutant melanoma
      population is being evaluated. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01738139, registered 28 November 2012.

PMID- 28428885
TI  - The Why, what, and How of the New FACT standards for immune effector cells.
AB  - Novel cellular therapies outside of traditional hematopoietic stem cell
      transplantation or hematopoietic progenitor cell (HPC) therapy are currently
      under evaluation in clinical trials across the United States and around the
      world. Several cellular products, e.g., CD19-directed Chimeric Antigen Receptor
      (CAR) T cells, are poised for FDA approval and thus increased use at a wider
      range of academic centers within the next year, with the likelihood of
      dissemination to standard oncology practice once safety is confirmed. However,
      these therapies entail some unique challenges in terms of logistics of delivery
      and toxicity management. Building on experiences and Standards established for
      HPC programs, the Foundation for the Accreditation of Cellular Therapy (FACT) has
      established new Standards specific to the use of Immune Effector Cells (IEC),
      including gene-modified T cells and natural (NK) cells. These Standards specify
      the clinical and quality infrastructure to facilitate safe administration of
      immune effector cells and formalize subsequent monitoring and reporting of
      patient outcomes to enable continual process improvement. Below we detail why
      these standards came into being, what they entail, and how a clinical team might
      access educational materials and implement these Standards. We propose that these
      Standards will be increasingly useful and relied up on as institutions and
      clinical service lines seek access to these treatment for their patients. FACT
      will begin accrediting programs that meet these new Standards for clinical
      administration of Immune Effector Cells in 2017.

PMID- 28428886
TI  - Vaccination with inhibin-alpha provides effective immunotherapy against
      testicular stromal cell tumors.
AB  - BACKGROUND: Testicular cancer is the most common male neoplasm occurring in men
      between the ages of 20 and 34. Although germ-line testicular tumors respond
      favorably to current standard of care, testicular stromal cell (TSC) tumors
      derived from Sertoli cells or Leydig cells often fail to respond to chemotherapy
      or radiation therapy and have a 5-year overall survival significantly lower than
      the more common and more treatable germ line testicular tumors. METHODS: To
      improve outcomes for TSC cancer, we have developed a therapeutic vaccine
      targeting inhibin-alpha, a protein produced by normal Sertoli and Leydig cells of
      the testes and expressed in the majority of TSC tumors. RESULTS: We found that
      vaccination against recombinant mouse inhibin-alpha provides protection and
      therapy against transplantable I-10 mouse TSC tumors in male BALB/c mice.
      Similarly, we found that vaccination with the immunodominant p215-234 peptide of
      inhibin-alpha (Inalpha 215-234) inhibits the growth of autochthonous TSC tumors
      occurring in male SJL.AMH-SV40Tag transgenic mice. The tumor immunity and
      enhanced overall survival induced by inhibin-alpha vaccination may be passively
      transferred into naive male BALB/c recipients with either CD4+ T cells, B220+ B
      cells, or sera from inhibin-alpha primed mice. CONCLUSIONS: Considering the lack
      of any alternative effective treatment for chemo- and radiation-resistant TSC
      tumors, our results provide for the first time a rational basis for immune
      mediated control of these aggressive and lethal variants of testicular cancer.

PMID- 28428888
TI  - Multimodal imaging findings in an adult case of Swyer-James-MacLeod syndrome.
AB  - Swyer-James-MacLeod syndrome (SJMS) is an uncommon obliterative lung disease that
      is radiologically characterized by hyperlucency of a part of or the entire lung.
      A 33-year-old man presented to our hospital for chest tightness. A chest X-ray
      revealed unilateral hyperlucency of left lower lung, and contrast-enhanced
      computed tomography (CT) of the chest disclosed a hyperlucent left lung without
      vascularity. Three-dimensional CT reconstruction and ventilation-perfusion scan
      findings were concordant with SJMS. We herein report a case of SJMS in a patient
      who showed the characteristic multimodal imaging findings.

PMID- 28428887
TI  - Differential intratumoral distributions of CD8 and CD163 immune cells as
      prognostic biomarkers in breast cancer.
AB  - BACKGROUND: Tumor immune cell infiltrates are essential in hindering cancer
      progression and may complement the TNM classification. CD8+ and CD163+ cells have
      prognostic impact in breast cancer but their spatial heterogeneity has not been
      extensively explored in this type of cancer. Here, their potential as prognostic
      biomarkers was evaluated, depending on their combined densities in the tumor
      center (TC) and the tumor invasive margin (IM). METHODS: CD8+ and CD163+ cells
      were quantified by immunohistochemistry of formalin-fixed, paraffin-embedded
      (FFPE) tumor tissue samples from a cohort totaling 162 patients with
      histologically-confirmed primary invasive non-metastatic ductal breast cancer
      diagnosed between 2000 and 2015. Clinical follow-up (median 6.9 years) was
      available for 97 of these patients. RESULTS: Differential densities of CD8+ and
      CD163+ cells in the combined TC and IM compartments (i.e., high(H)/low(L),
      respectively for CD8+ cells and the reverse L/H combination for CD163+ cells)
      were found to have significant prognostic value for survival, and allowed better
      patient stratification than TNM stage, tumor size, lymph node invasion and
      histological grade. The combined evaluation of CD8+ and CD163+ cell densities
      jointly in TC and IM further improves prediction of clinical outcomes based on
      disease-free and overall survival. Patients having the favorable immune
      signatures had favorable clinical outcomes despite poor clinicopathological
      parameters. CONCLUSIONS: Given the important roles of CD8+ and CD163+ cells in
      regulating opposing immune circuits, adding an assessment of their differential
      densities to the prognostic biomarker armamentarium in breast cancer would be
      valuable. Larger validation studies are necessary to confirm these findings.
      TRIAL REGISTRATIONS: Study code: IRB-ID 6079/448/10-6-13 Date of approval:
      10/06/2013 Retrospective study (2000-2010) First patient prospectively enrolled
      14/2/2014.

PMID- 28428889
TI  - Detection of 1p36 deletion by clinical exome-first diagnostic approach.
AB  - Although chromosome 1p36 deletion syndrome is considered clinically recognizable
      based on characteristic features, the clinical manifestations of patients during
      infancy are often not consistent with those observed later in life. We report a 4
      month-old girl who showed multiple congenital anomalies and developmental delay,
      but no clinical signs of syndromic disease caused by a terminal deletion in
      1p36.32-p36.33 that was first identified by targeted-exome sequencing for
      molecular diagnosis.

PMID- 28428890
TI  - Asthma in the elderly: a double-blind, placebo-controlled study of the effect of
      montelukast.
AB  - BACKGROUND: Little is known about asthma in the elderly as most studies of this
      condition have not included this patient group. It is unclear whether leukotriene
      antagonists benefit older asthmatics. We studied the effect of adding montelukast
      to the asthma treatment of elderly subjects. METHODS: Twenty-five subjects 65
      years old and older with asthma were evaluated at week 0, 1, 5, 9, 13, and 17.
      Each subject received montelukast 10 mg and placebo each for 8 weeks in a cross
      over design. RESULTS: Montelukast for 4 or 8 weeks did not significantly affect
      ACT, daily symptom scores, number of puffs of albuterol, spirometric values,
      peripheral blood eosinophils, or serum IgE vs. baseline or placebo. Similar
      results were obtained when analyzing subgroups of patients with lower ACT, lower
      FEV1, and higher eosinophils. CONCLUSIONS: In this study of elderly asthmatics,
      montelukast had no effect on asthma symptoms, number of puffs of albuterol,
      spirometric values, peripheral blood eosinophils or serum IgE. These results will
      require confirmation in larger patient cohorts and in patients with uncontrolled
      asthmatic symptoms.

PMID- 28428891
TI  - Dietary inclusion effects of phytochemicals as growth promoters in animal
      production.
AB  - Growth promoters have been widely used as a strategy to improve productivity, and
      great benefits have been observed throughout the meat production chain. However,
      the prohibition of growth promoters in several countries, as well as consumer
      rejection, has led industry and the academy to search for alternatives. For
      decades, the inclusion of phytochemicals in animal feed has been proposed as a
      replacement for traditional growth promoters. However, there are many concerns
      about the application of phytochemicals and their impact on the various links in
      the meat production chain (productive performance, carcass and meat quality).
      Therefore, the effects of these feed additives are reviewed in this article,
      along with their potential safety and consumer benefits, to understand the
      current state of their use. In summary, the replacement of traditional growth
      promoters in experiments with broilers yielded benefits in all aspects of the
      meat production chain, such as improvements in productive performance and carcass
      and meat quality. Although the effects in pigs have been similar to those
      observed in broilers, fewer studies have been carried out in pigs, and there is a
      need to define the types of phytochemicals to be used and the appropriate stages
      for adding such compounds. In regard to ruminant diets, few studies have been
      conducted, and their results have been inconclusive. Therefore, it is necessary
      to propose more in vivo studies to determine other strategies for phytochemical
      inclusion in the production phases and to select the appropriate types of
      compounds. It is also necessary to define the variables that will best elucidate
      the mechanism(s) of action that will enable the future replacement of synthetic
      growth promoters with phytochemical feed additives.

PMID- 28428892
TI  - A comparison of earlier and enhanced rehabilitation of mechanically ventilated
      patients in critical care compared to standard care (REHAB): study protocol for a
      single-site randomised controlled feasibility trial.
AB  - BACKGROUND: Mortality from critical illness is improving, but survivors suffer
      from prolonged weakness and psychological and cognitive impairments. Maximising
      the recovery after critical illness has been highlighted as a research priority,
      especially in relation to an ageing population who present with higher rates of
      pre-morbid disability. Small studies have shown that starting rehabilitation
      early within the intensive care unit (ICU) improves short-term outcomes.
      Systematic reviews have highlighted the need for robust multicentre randomised
      controlled trials with longer term follow-up. METHODS: The study design is a
      randomised controlled study to explore the feasibility of providing earlier and
      enhanced rehabilitation to mechanically ventilated patients at high risk of ICU
      acquired weakness within the ICU. The rehabilitation intervention involves a
      structured programme, with progression along a functionally based mobility
      protocol according to set safety criteria. The overall aim of the intervention is
      to commence mobilisation at an earlier time point in the patient's illness and
      increase mobility of the patient through their recovery trajectory. Participants
      will be randomised to enhanced rehabilitation or standard care, with the aim of
      recruiting at least 100 patients over 16 months. The trial design will assess
      recruitment and consent rates from eligible patients, compliance with the
      intervention, and assess a range of possible outcome measures for use in a
      definitive trial, with follow-up continuing for 12 months post hospital
      discharge. DISCUSSION: This study will evaluate the feasibility of providing an
      earlier and enhanced rehabilitation intervention to mechanically ventilated
      patients in critical care. We will identify strengths and weaknesses of the
      proposed protocol and the utility and characteristics of the outcome measures.
      The results from this study will inform the design of a phase III multicentre
      trial of enhanced rehabilitation for critically ill adults. TRIAL REGISTRATION:
      ISRCTN90103222, 13/08/2015; retrospectively registered.

PMID- 28428893
TI  - Characteristics and racial variations of polypoidal choroidal vasculopathy in
      tertiary centers in the United States and United Kingdom.
AB  - PURPOSE: To evaluate the characteristics and racial variations amongst patients
      with polypoidal choroidal vasculopathy (PCV) in the United States and the United
      Kingdom. METHODS: Fundus photos and indocyanine green angiography images were
      evaluated in a multicenter retrospective study to establish the diagnosis of PCV.
      Visual acuity (VA) was recorded in ETDRS letter count. RESULTS: Eighty eyes of 71
      PCV patients (average age of 69.4 +/- 10.4 years) were included in the analysis.
      Of the total 71 subjects, 46 (65%) were women, 33 (46.5%) were Blacks, 16 (22.5%)
      were Whites, 19 (26.8%) were Asians and 3 (4.2%) belonged to other races. The
      Black subgroup had vision gain of 3.5 letters. The White and Asian subgroups had
      vision loss of 13.1 and 3.5 letters, respectively. There was female predominance
      in Blacks (67%), Whites (69%), and Asians (58%). PCV was found to be a bilateral
      disease in 14 patients (20%). There was significant decrease of 7 letters with
      every decade increase in age (p = 0.005). Final VA was worse in males when
      compared to females (p = 0.042), and worse in Whites when compared to Blacks (p =
      0.005). For every 10 letters worse in initial VA upon diagnosis with PCV, the
      final VA was worse by 6 letters (p < 0.001). The location of the polypoidal
      lesion within the macula was associated with significant decrease of 14 letters
      in BCVA (p = 0.02). The length of follow up was significantly associated with
      worse visual outcome (p = 0.012). Final VA had no significant correlation with
      the lens status, or the different treatment modalities. CONCLUSIONS: Based on our
      cohort from tertiary centers in the United States and United Kingdom, PCV is a
      bilateral disease in one-fifth of patients. It features a variable female
      predominance based on ethnicity. Increased age, worse vision upon initial
      presentation, longer follow up and macular location of the polyp were associated
      with worse visual outcome.

PMID- 28428894
TI  - The Protective Role of Hyaluronic Acid in Cr(VI)-Induced Oxidative Damage in
      Corneal Epithelial Cells.
AB  - Cr(VI) exposure could produce kinds of intermediates and reactive oxygen species,
      both of which were related to DNA damage. Hyaluronan (HA) has impressive
      biological functions and was reported to protect corneal epithelial cells against
      oxidative damage induced by ultraviolet B, benzalkonium chloride, and sodium
      lauryl sulfate. So the aim of our study was to investigate HA protection on human
      corneal epithelial (HCE) cells against Cr(VI)-induced toxic effects. The HCE cell
      lines were exposed to different concentrations of K2Cr2O7 (1.875, 3.75, 7.5,
      15.0, and 30 MUM) or a combination of K2Cr2O7 and 0.2% HA and incubated with
      different times (15 min, 30 min, and 60 min). Our data showed that Cr(VI)
      exposure could cause decreased cell viability, increased DNA damage, and ROS
      generation to the HCE cell lines. But incubation of HA increased HCE cell
      survival rates and decreased DNA damage and ROS generation induced by Cr(VI) in a
      dose- and time-dependent manner. We report for the first time that HA can protect
      HCE cells against the toxicity of Cr(VI), indicating that it will be a promising
      therapeutic agent to corneal injuries caused by Cr(VI).

PMID- 28428895
TI  - Suppression of Retinal Neovascularization by Inhibition of Galectin-1 in a Murine
      Model of Oxygen-Induced Retinopathy.
AB  - Galectin-1 (Gal-1) has been proved to be an important factor in the process of
      tumor angiogenesis recently. As a small molecule, OTX008 serves as a selective
      inhibitor of Gal-1. In this study, the role of Gal-1 and the antiangiogenic
      effect of OTX008 on retinal neovascularization (RNV) were investigated using a
      mouse model of oxygen-induced retinopathy. The outcome indicated that Gal-1 was
      overexpressed and closely related to retinal neovessels in OIR. After
      intravitreal injection of OTX008 at P12, the RNV was significantly reduced at
      P17, measuring by cross-sectional H&E staining and whole-mount fluorescence. Our
      results demonstrate the inhibitory function of OTX008 on RNV, which provides a
      promising strategy of treating retinal angiogenic diseases such as retinopathy of
      prematurity and proliferative diabetic retinopathy.

PMID- 28428896
TI  - Successful Treatment of Facial Acne Fulminans: Antimicrobial Agents and Oral
      Prednisolone as Promising Regimes.
AB  - Acne fulminans (AF), also known as acne maligna, is a rare painful ulcerative
      form of acne with an abrupt onset and systemic symptoms. Its incidence appears to
      be decreasing, possibly because of earlier and better treatment of acne. This
      report highlights a case on a necrotizing facial wound due to AF that was
      successfully treated with oral prednisolone and antimicrobial medication.

PMID- 28428897
TI  - Acute Myeloid Leukemia with Basophilic Differentiation Transformed from
      Myelodysplastic Syndrome.
AB  - Myelodysplastic syndrome (MDS) terminally transforms to acute myeloid leukemia
      (AML) or bone marrow failure syndrome, but acute myeloid leukemia with basophilic
      differentiation has been rarely reported. An 81-year-old man was referred to our
      department for further examination of intermittent fever and normocytic anemia
      during immunosuppressive treatment. Chromosomal analysis showed additional
      abnormalities involving chromosome 7. He was diagnosed as having MDS. At the time
      of diagnosis, basophils had not proliferated in the bone marrow. However, his
      anemia and thrombocytopenia rapidly worsened with the appearance of peripheral
      basophilia three months later. He was diagnosed as having AML with basophilic
      differentiation transformed from MDS. At that time, monosomy 7 was detected by
      chromosomal analysis. We found that basophils can be confirmed on the basis of
      the positivity for CD203c and CD294 by flow cytometric analysis. We also found by
      cytogenetic analysis that basophils were derived from myeloblasts. He refused any
      chemotherapy and became transfusion-dependent. He died nine months after the
      transformation. We should keep in mind that MDS could transform to AML with
      basophilic differentiation when peripheral basophilia in addition to myeloblasts
      develops in patients with MDS.

PMID- 28428898
TI  - Severe Acute Hepatitis B in HBV-Vaccinated Partner of a Patient with Multiple
      Myeloma Treated with Cyclophosphamide, Bortezomib, and Dexamethasone and
      Autologous Stem Cell Transplant.
AB  - Hepatitis B reactivation can occur with various forms of immunosuppression.
      Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is
      commonly used for the treatment of multiple myeloma and has not been noted in
      guidelines to be causative in HBV reactivation. Indeed, current guidelines do not
      recommend providing antiviral prophylaxis to patients with prior HBV infection.
      We present a case of HBV reactivation as a result of CYBOR-D and autologous stem
      cell transplant which is complicated by the patient's partner who developed acute
      hepatitis B. Our case highlights the need to review the role of antiviral
      prophylaxis for patients undergoing treatment of multiple myeloma and also the
      role of ensuring immunity for close contacts of these patients who may also be at
      risk.

PMID- 28428899
TI  - Watershed Infarct in Beta-Thalassemia Major Patient.
AB  - Background. The mechanism of stroke in beta-thalassemia was reported previously
      as cardioembolic and hypercoagulable state. However, there is no report of
      watershed infarct in beta-thalassemia anemia. Method. We present an adult beta
      thalassemia major patient with manifest asymptomatic chronic left carotid
      occlusion who suffered watershed infarct. Result. In the presence of asymptomatic
      chronic left internal carotid occlusion, we assumed that severe anemia
      (hemoglobin = 3) at admission leads to watershed infarct. Conclusion. Watershed
      infarct seems to be the cause of stroke in cases of beta-thalassemia major with
      severe anemia. Blood transfusion can be applied in the setting of acute brain
      ischemia in such high risk patients.

PMID- 28428900
TI  - Asymptomatic Severe Vagal and Sympathetic Cardiac Denervation in Holmes-Adie's
      Syndrome.
AB  - A 40-year-old woman was found to have bilateral Adie's pupils and generalized
      muscle stretch areflexia. She did not have orthostatic hypotension but, in an ECG
      strip in the office, she appeared to have an almost fixed heart rate. We thus
      studied the heart rate variability (HRV) and the systolic blood pressure
      variability (SBPV) in supine and standing position and also during rhythmic
      breathing. We found a decreased HRV in the time domain with very low standard
      deviation in supine and standing position and during rhythmic breathing. HRV in
      the frequency domain was low with a decrease in the absolute power of HF and LF
      and a decrease in the sympathovagal balance in supine and standing positions.
      SBPV in the time and frequency domains was found to be normal. This patient with
      Holmes-Adie syndrome had an asymptomatic severe loss of HRV and a preserved SBPV.
      The global decrease in the HRV in the time and frequency domains indicated that
      she had both vagal and sympathetic cardiac denervation, whereas the preserved
      SBPV suggested normal innervation of the blood vessels.

PMID- 28428901
TI  - Microcystic/Reticular Schwannoma of the Frontal Lobe: An Unusual Occurrence.
AB  - Schwannoma is a benign peripheral nerve sheath tumor that typically involves
      cranial nerves of the head and neck region. Intraparenchymal occurrence of this
      tumor is uncommon. Even rarer in this site is the microcystic/reticular pattern
      of schwannoma. This histologic variant, first described in 2008, has a
      predilection for visceral organs. Herein, we report the first case of
      microcystic/reticular schwannoma of the frontal lobe.

PMID- 28428902
TI  - Nonfamilial Juvenile Polyposis Syndrome with Exon 5 Novel Mutation in SMAD 4
      Gene.
AB  - Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary
      disorder, characterized by multiple juvenile polyps in the gastrointestinal tract
      and an increased risk of colorectal cancer. JPS is most frequently caused by
      mutations in the SMAD4 or BMPR1A genes. Herein, we report a child with juvenile
      polyposis syndrome (JPS) with a novel mutation in the SMAD4 gene. An 8-year-old
      boy presented with recurrent rectal bleeding and was found to have multiple
      polyps in the entire colon. The histology of the resected polyps was consistent
      with juvenile polyps. Subsequent genetic screening revealed a novel mutation in
      SMAD4, exon 5 (p.Ser144Stop). To the best of our knowledge, this mutation has not
      been reported before. Offering genotypic diagnosis for patients with JPS is an
      important step for strategic plan of management.

PMID- 28428903
TI  - SLE and Non-Hodgkin's Lymphoma: A Case Series and Review of the Literature.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder
      punctuated by varied multiorgan complications all along the course of its natural
      history. Lymphoma represents a relatively well-recognized malignant phenomenon
      associated with lupus. The cause and effect relationships of lymphoma in SLE have
      been subject to extensive scrutiny with several studies reporting on clinic
      pathologic characteristics and risk factors predicting lymphoma development in
      SLE. However, the pathogenic role of immunosuppressives in SLE-related lymphoma
      still remains unclear, and indices to help guide diagnosis, prognostication,
      therapy, and posttreatment monitoring are yet to be established. In this review,
      we describe 3 SLE patients who developed non-Hodgkin's lymphoma at different time
      points of their disease. Through a careful dissection of the aforementioned
      cases, we intend to apprise readers of the currently available literature
      surrounding risk factors, management, and prognosis in SLE-related lymphoma. We
      will also review and discuss the implications of immunosuppressives in SLE
      related lymphoma and the role of mycophenolate mofetil in SLE-related primary CNS
      lymphoma development.

PMID- 28428905
TI  - Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease
      Patient with Significant Tremor and Comorbid Depression.
AB  - CLINICAL VIGNETTE: A 67-year-old female with advanced Parkinson's disease (PD),
      medically refractory tremor, and a history of significant depression presented
      for evaluation of deep brain stimulation (DBS) candidacy. CLINICAL DILEMMA:
      Traditionally, the subthalamic nucleus (STN) has been preferred over the globus
      pallidus interna (GPi) as a DBS target for PD patients with levodopa-responsive
      fluctuations in rigidity and akinesia, for whom tremor is also a significant
      source of impairment. However, STN stimulation is avoided in patients with a
      significant pre-surgical history of mood disorder. CLINICAL SOLUTION: Bilateral
      DBS of the GPi led to significant short-term improvement in PD motor symptoms,
      including significant tremor reduction. GAP IN KNOWLEDGE: There is insufficient
      evidence to support or refute clinicians' traditional preference for STN
      stimulation in treating refractory PD tremor. Similarly, the available evidence
      for risk of worsening depression and/or suicidality after STN DBS is mixed. Both
      questions require further clarification to guide patient and clinician decision
      making.

PMID- 28428904
TI  - Salvage of Necrotic-Appearing Limb after In Utero Endoscopic Lysis of
      Constriction Bands.
AB  - We report a case of amniotic band syndrome complicated by constriction bands and
      marked distal swelling of both lower extremities. Color Doppler interrogation of
      the right lower extremity revealed complete lack of blood flow below the level of
      the constriction. Upon fetoscopic survey, the right lower extremity beyond the
      constriction band appeared dusky red and discolored with desquamation, consistent
      with a necrotic appearance. The constriction bands were cut in utero using
      endoshears, thereby allowing restoration of blood flow on postoperative day 1.
      The patient was counseled extensively regarding the possibility of limb
      dysfunction or amputation. However, the baby was born with functional lower
      extremities, and at 21 months of age, the child was cruising and jumping on his
      own. This case demonstrates that there is unique plasticity in fetal limb
      recovery after a severe ischemic injury that is not otherwise seen in postnatal
      life. Reperfusion of the necrotic-appearing limb resulted in restoration of
      appearance and function without apparent deleterious effects on the fetus. We
      believe the favorable outcome in this case was likely due to timeliness of the in
      utero lysis of amniotic bands and the plasticity of fetal healing.

PMID- 28428906
TI  - TBC1D24 Mutations in a Sibship with Multifocal Polymyoclonus.
AB  - BACKGROUND: Advances in molecular genetic technologies have improved our
      understanding of genetic causes of rare neurological disorders with features of
      myoclonus. CASE REPORT: A family with two affected siblings, presenting with
      multifocal polymyoclonus and neurodevelopmental delay, was recruited for whole
      exome sequencing following unyielding diagnostic neurometabolic investigations.
      Compound heterozygous mutations in TBC1D24, a gene previously associated with
      various epilepsy phenotypes and hearing loss, were identified in both siblings.
      The mutations included a missense change c.457G>A (p.Glu157Lys), and a novel
      frameshift mutation c.545del (p.Thr182Serfs*6). DISCUSSION: We propose that
      TBC1D24-related diseases should be in the differential diagnosis for children
      with polymyoclonus.

PMID- 28428907
TI  - Palliative Care in Huntington Disease: Personal Reflections and a Review of the
      Literature.
AB  - BACKGROUND: Huntington disease is a fatal, autosomal dominant, neurodegenerative
      disorder manifest by the triad of a movement disorder, behavioral disturbances,
      and dementia. At present, no curative or disease modifying therapies exist for
      the condition and current treatments are symptomatic. Palliative care is an
      approach to care that focuses on symptom relief, patient and caregiver support,
      and end of life care. There is increasing evidence of the benefit of palliative
      care throughout the course of neurodegenerative conditions including Parkinson
      disease and amyotrophic lateral sclerosis. However, beyond its application at the
      end of life, little is known about the role of palliative care in Huntington
      disease. METHODS: In this article, we discuss what is known about palliative care
      in Huntington disease, specifically related to early disease burden, caregiver
      burnout, advance care planning, and end of life care. RESULTS: We provide a
      review of the current literature and discuss our own care practices. DISCUSSION:
      We conclude by discussing questions that remain unanswered and positing ideas for
      future work in the field.

PMID- 28428908
TI  - Metastatic squamous cell carcinoma of colon from esophageal cancer.
AB  - BACKGROUND: Esophageal cancer including squamous cell carcinoma (SCC) and
      adenocarcinoma represents 4% of all cancers in the United States. Patients with
      esophageal cancer frequently present with locally advanced disease, and about 40%
      of patients have evidence of metastatic disease on presentation. Common sites of
      metastasis include liver, lung and bone. Here, we present a rare case of colonic
      metastasis from primary esophageal SCC. CASE PRESENTATION: A 60-year-old
      Caucasian male with a history of 20-pack-year cigarette smoking received surgery
      and adjuvant chemoradiotherapy for locally advanced SCC of larynx. Approximately
      9 months later, he developed dysphagia, and found to have a esophageal SCC in the
      mid-esophagus with regional lymph node involvement. He underwent chemoradiation
      treatment with good response and improved symptoms but declined subsequent
      surgical resection for esophageal cancer. About 1 year after the diagnosis of
      esophageal cancer, he developed blood streaked bowel movement and severe anemia.
      Colonoscopy showed a 3-cm mass in the proximal ascending colon; biopsy showed
      metastatic SCC, consistent with metastasis from esophageal primary. He
      subsequently received palliative radiation to the ascending colon metastatic
      tumor with improvement of anemia, and remained transfusion independent for more
      than 3 months. CONCLUSIONS: Colonic metastasis from esophageal SCC is rare, and
      associated with poor prognosis. There are no definite features in terms of
      location, histological differentiation etc. that contribute to colonic metastasis
      from primary esophageal SCC. The goal of treatment is palliative and data from
      our and other case reports support the use of chemotherapy and radiation for
      symptom improvement and disease control.

PMID- 28428909
TI  - A Biomechanical Perspective on Distal Radioulnar Joint Instability.
AB  - Background The purpose of this article was to review the anatomy, kinematics of
      the distal radioulnar joint (DRUJ), and to discuss definition, classification,
      and diagnosis of DRUJ instability. Methods A biomechanical perspective on
      physical examination of DRUJ ballottement test was documented. Physiological
      dynamic DRUJ translation and differences of the translation following sequential
      ligament sectioning and changes in different forearm and wrist positions were
      demonstrated. The clinical significance of each ligament's contribution to joint
      stability in specific wrist positions was addressed. Conclusion Each ligament
      stabilizing the DRUJ contributed to joint stability depending on the direction
      (palmer or dorsal) and different positions of the wrist and forearm. DRUJ
      ballottement test in each wrist and forearm position may detect tears of specific
      ligament stabilizing the DRUJ.

PMID- 28428910
TI  - Role of the Interosseous Membrane in Preventing Distal Radioulnar Gapping.
AB  - Background Damage to the interosseous membrane (IOM) can alter load transmission
      between the radius and ulna and decrease their axial stability. Less is known
      about the effect of IOM sectioning on the transverse stability between the radius
      and ulna. Purpose The purpose of this study was to quantify the radioulnar
      gapping at the distal radioulnar joint (DRUJ) during forearm rotation when the
      IOM was experimentally sectioned while maintaining the integrity of the distal
      radioulnar ligaments. Methods In 12 fresh-frozen cadaver forearms tested in a
      combined wrist-forearm simulator, the increase in gap between the radius and
      ulna, at the level of the DRUJ, was determined during cyclic forearm rotation
      following IOM sectioning. Results IOM sectioning caused a significant increase in
      dorsal gapping at the DRUJ by 2.1 mm in supination and 0.6 mm in pronation. It
      also caused an increase in palmar gapping by 1.3 mm in supination and 0.5 mm in
      pronation. Conclusion This experiment has shown that the IOM has an important
      role in stabilizing the DRUJ, especially in supination, and that IOM sectioning
      caused greater loads on the palmar and dorsal radioulnar ligaments. Since DRUJ
      instability is primarily treated by fixing the laxity at the dorsal radioulnar
      ligament (DRUL) and palmar radioulnar ligament (PRUL), untreated IOM damage could
      permit additional injury and instability to the radioulnar ligaments or their
      reconstruction. Clinical Relevance Reconstruction of a torn IOM should be
      considered in the presence of persistent DRUJ instability following DRUJ
      reconstruction.

PMID- 28428911
TI  - Early Rehabilitation of Distal Radius Fractures Stabilized by Volar Locking
      Plate: A Prospective Randomized Pilot Study.
AB  - Background Distal radius fractures are very common and an increased incidence of
      50% is estimated by 2030. Therefore, both operative and postsurgical treatment
      remains pertinent. Main aim in treating intra-articular fractures is to restore
      the articular surface by internal fixation and early mobilization (EM).
      Questions/Purposes The purpose of this study was to compare functional results
      between EM immediately after surgery and 5 weeks of immobilization (IM). Patients
      and Methods In a randomized prospective study, 30 patients with an isolated
      distal radius fracture were treated by open reduction and internal fixation using
      a single volar locking plate excluding bone graft. Fifteen patients were
      randomized in the EM group and 15 in the IM group. At 6 weeks, 9 weeks, 3 months,
      6 months, and 1 year postsurgery, range of motion, grip strength and X-rays were
      evaluated. Additionally, Quick Disability of the Arm, Shoulder and Hand
      (QuickDASH) questionnaire, Patient-Rated Wrist Evaluation (PRWE), modified Green
      O'Brien (Mayo) score, and pain according to the Visual Analog Scale score were
      analyzed. Results Patients in the EM group had a significantly better range of
      motion in the sagittal plane, in grip strength up to 6 months, in the frontal
      plane up to 9 weeks, and in forearm rotation up to 6 weeks. Also QuickDASH and
      PRWE scores were better up to 6 weeks postsurgery. The Green O'Brien score
      differed significantly up to 1 year. At 1 year, 93% "excellent" and "good"
      results in the Green O'Brien score with a mean QuickDASH of 5.98 +/- 10.94 and
      PRWE score of 4.27 +/- 9.23 were observed in the EM group. No differences
      regarding loss of reduction, pain, duration of physiotherapy, and sick leave were
      noted. Conclusion EM of surgically treated distal radius fractures (without bone
      graft) is a safe method for postoperative aftercare and leads to an improved
      range of motion and grip strength at 6 months postsurgery compared with an IM of
      5 weeks. Level of Evidence This is a level Ib clinical study.

PMID- 28428912
TI  - Biomechanical Evaluation of Carpal Kinematics during Simulated Wrist Motion.
AB  - Background Flexion and extension of the wrist is achieved primarily at the
      radiocarpal and midcarpal joints. Carpal kinematics have been investigated,
      although there remains no consensus regarding the relative contribution of each
      bone to wrist motion. Purpose To determine the kinematics of the scaphoid,
      lunate, and capitate during unconstrained simulated wrist flexion/extension and
      to examine the effect of motion direction on the contribution of each bone.
      Materials and Methods Seven cadaveric upper extremities were tested in a passive
      wrist simulator with 10N tone loads applied to the wrist flexors/extensors.
      Scaphoid, lunate, and capitate kinematics were captured using optical tracking
      and analyzed with respect to the radius. Results Scaphoid and lunate motion
      correlated linearly with wrist motion (R2 = 0.99, 0.97). In extension, the
      scaphoid and lunate extended 83 +/- 19% and 37 +/- 18% relative to total wrist
      extension (p = 0.03, 0.001), respectively. In flexion, the scaphoid and lunate
      flexed 95 +/- 20% and 70 +/- 12% relative to total wrist flexion (p = 1.0,0.01) ,
      respectively. The lunate rotated 46 +/- 25% less than the capitate and 35 +/- 31%
      less than the scaphoid. The intercarpal motion between the scaphoid and lunate
      was 25 +/- 17% of wrist flexion. Conclusion The scaphoid, lunate, and capitate
      move synergistically throughout planar wrist motion. The scaphoid and lunate
      contributed at a greater degree during flexion, suggesting that the radiocarpal
      joint plays a more critical role in wrist flexion. Clinical Relevance The large
      magnitude of differential rotation between the scaphoid and lunate may be
      responsible for the high incidence of scapholunate ligament injuries. An
      understanding of normal carpal kinematics may assist in positioning carpal bones
      during partial wrist fusions and in developing more durable wrist arthroplasty
      designs.

PMID- 28428913
TI  - Comparison of Magnetic Resonance Imaging and Radiographs for Evaluation of Carpal
      Osteoarthritis.
AB  - Background We sought to evaluate the interobserver and intraobserver reliability
      of radiographs and magnetic resonance imaging (MRI) for grading of osteoarthritis
      in patients with scapholunate advanced collapse (SLAC) and scaphoid nonunion
      advanced collapse (SNAC), and to determine whether MRI is more likely than
      radiographs to detect carpal osteoarthritis. Methods Radiographs and MR studies
      of 46 patients with SLAC and SNAC arthritis were reviewed by two hand surgeons
      and two radiologists and were graded according to severity of osteoarthritis at
      seven carpal joints. Interobserver and intraobserver reliability was assessed
      using a weighted kappa analysis. Odds ratios were calculated to compare the
      likelihood of MRI versus radiographs in the determination of moderate or severe
      osteoarthritis. Results Measures of reliability were higher for MRI than
      radiographs. For radiographic assessment of all patients combined, interobserver
      agreement was moderate and intraobserver agreement was also moderate. For MRI,
      interobserver agreement was substantial and intraobserver agreement was almost
      perfect. In all joints combined for patients with SLAC and SNAC, MRI was 2.42
      times more likely to demonstrate moderate osteoarthritis compared with
      radiographs. In patients with SLAC, MRI was 11.73 times more likely than
      radiographs to show moderate osteoarthritis at the radiolunate joint. In patients
      with SNAC, there was no difference in demonstration of moderate osteoarthritis on
      MRI compared with radiographs. Conclusion Carpal osteoarthritis can be more
      reliably assessed on MRI than radiographs. MRI is more sensitive at demonstrating
      moderate changes of osteoarthritis than radiographs, especially at the
      radiolunate joint in patients with SLAC arthritis. This has implications for
      surgical management of SLAC/SNAC arthritis and preoperative planning. MRI should
      be included in the diagnostic workup and evaluation of patients with SLAC and
      SNAC arthritis. Level of Evidence Diagnostic III.

PMID- 28428914
TI  - Development and Validation of a Disease-Specific Questionnaire for Basal Joint
      Arthritis.
AB  - Background The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire
      is the most commonly used instrument to assess outcomes of basal joint arthritis
      (BJA). However, the DASH is subject to influence by the entire upper extremity.
      Purpose This study aims to develop and validate a disease-specific questionnaire
      for BJA that would be more sensitive to changes in thumb function and pain, and
      correlate better with objective and subjective metrics. Patients and Methods The
      thumb disability examination (TDX) was developed and 80 patients presenting with
      BJA at one of the two hospital-based hand clinics were enrolled in the validation
      study. At enrollment, subjects were given the TDX, DASH, and visual analog pain
      scale with activity (A-VAS) surveys. The strength was assessed. Patients
      receiving corticosteroid injection were seen for follow-up at 6 weeks and those
      who underwent surgery were seen between 3 and 6 months postoperatively. Both the
      groups were given the TDX, DASH, and A-VAS scales at follow-up. Results In total,
      65 subjects were included in the analysis. Average TDX completion time was 134.3
      seconds. The TDX correlated more strongly with A-VAS scores at baseline than the
      DASH, but less strongly with tip-pinch measures. The TDX was more responsive to
      injection and surgical treatments for BJA than the DASH, yielding a larger effect
      size and standardized response mean, and was the only instrument to significantly
      correlate with changes in A-VAS. Conclusion The TDX is a reliable instrument for
      assessing BJA treatment outcomes. It bears less of a burden on patients, is more
      responsive to symptomatic changes, and correlates better with most objective and
      subjective measures than the DASH. Level of Evidence II, diagnostic.

PMID- 28428916
TI  - Extensor Carpi Ulnaris Instability Following Ulnar Shortening Osteotomy.
AB  - Background Ulnar shortening osteotomy (USO) is a well-established procedure for
      the treatment of ulnar impaction syndrome. Although uncommon, the procedure can
      be associated with complications including nonunion, malunion, and hardware
      irritation. Case Description We present a 56-year-old woman who developed
      extensor carpi ulnaris (ECU) tendon instability following an USO. Literature
      Review The etiology of such a complication can be multifactorial. Clinical
      Relevance The recurrence of ulnar pain following an USO should raise the
      suspicion of possible ECU instability within the differential diagnosis.

PMID- 28428915
TI  - Pyrolytic Carbon Arthroplasty versus Suspensionplasty for Trapezial-Metacarpal
      Arthritis.
AB  - Purpose This study aims to compare outcomes after pyrolytic carbon implant
      hemiarthroplasty (PH) versus Thompson suspensionplasty (TS) for trapezial
      metacarpal (TM) arthritis. Patients and Methods There were 87 arthritic TM joints
      in 71 patients treated with PH (n = 47 joints, 37 patients) or TS (n = 40 joints,
      34 patients). Patients had significantly longer follow-up in the TS group (86.9
      months, 25th-75th percentile = 55.6-103.8) versus the PH group (38.4 months, 25th
      75th percentile = 23.2-65.8, p < 0.001). Results PH patients maintained higher
      final grip strength (p = 0.03) and apposition pinch strength (p = 0.01) compared
      with TS patients. Nelson scores were significantly higher among patients
      undergoing PH (mean = 50.4, standard deviation [SD] = 24.5) compared with TS
      (mean = 36.8, SD = 12.5, p < 0.01). There was a significantly higher proportion
      of complications (p < 0.01), reoperations (p < 0.01), and joint revision surgery
      (p < 0.01) in patients undergoing PH compared with TS. Controlling for age and
      sex, there was a 72.8% lower risk of complications (p = 0.02), 87.7% lower risk
      of reoperations (p = 0.01), and 87.2% lower risk of joint revision surgery (p <
      0.01) among patients undergoing TS compared with PH. There was a shorter time to
      first complication (p < 0.01), reoperation (p < 0.02), and joint revision (p <
      0.01) in those undergoing PH compared with TS. Conclusion Both cohorts exhibited
      functional range of motion and pinch and grip strengths postoperatively, and
      those undergoing PH began with and maintained higher grip and pinch strength at
      final follow-up. Those undergoing PH had significantly increased risk of
      complications, reoperations, and joint revision surgery. Most complications in
      patients undergoing PH were related to suspected development of
      scaphotrapezotrapezoidal (STT) arthritis postoperatively. We thus recommend
      careful evaluation of possible STT arthritis when considering PH arthroplasty.
      Level of Evidence Level III.

PMID- 28428917
TI  - Ulnolunate Ligament Avulsion Fracture of the Lunate: A Case Report.
AB  - Traumatic lunate fractures are very rare and those treatments require an
      understanding of anatomical features. We present a case of an ulnolunate ligament
      avulsion fracture of the lunate that was successfully repaired by surgical
      fixation with open reduction and internal fixation. We believe that restoration
      of ulnolunate ligament function is important to prevent further deterioration of
      wrist function after this injury.

PMID- 28428918
TI  - The Safety of the Thenar Portal: An Anatomical Study of the Thumb Carpometacarpal
      Arthroscopy.
AB  - Purpose To define the localization of the distal course of the motor branches of
      median nerve (MBMN) and its arborization and its quantitative relationships to
      the thenar portal of the carpometacarpal (CMC) joint in the hope of evaluating
      the safety of this portal. Method In 16 embalmed cadaveric upper extremities, the
      localization of the course of the MBMN and its arborization were defined. In 14
      fresh-frozen cadaver upper extremities, the CMC arthroscopic portals, 1-U, 1-R,
      and a thenar portal, were established, after which the limbs were dissected.
      Measurements were taken from the portals to the superficial radial nerve, radial
      artery, and the MBMN. Results The distal course of the MBMN and its terminal
      branches were all located in the proximal third of the thenar muscles, where the
      thenar portal was introduced. The mean distances between vital structures and
      each traditional portal (1-R or 1-U) were consistent with the previously
      published studies. Both the superficial and the profound branches of MBMN were
      very close to the thenar portal, and the distance between these two main terminal
      branches and the thenar portal was 1.2 mm (range: 0-6.2; standard deviation [SD]
      = 2) and 2.2 mm (range: 0-7; SD = 2.1), respectively. Five (35.7%) of the 14
      fresh-frozen specimens indicated the superficial branch lay directly over the
      portal. One hand (7.1%) had the profound branch crossed over the thenar portal.
      Four hands (28.5%) indicated both the superficial and profound branches directly
      overlay the thenar portal. The superficial palmar branch of the radial artery was
      found in six hands, and in four of them, it crossed over the thenar portal.
      Conclusion The distal course of the MBMN and its terminal branches were all
      located in the proximal third of the thenar muscles, where the thenar portal was
      introduced. Clinical Relevance The thenar portal could improve the view of the
      CMC joint of the thumb and provide better performance of procedures in this
      joint. We should bear in mind that the arborization of the MBMN was mostly
      located in the proximal third of the thenar muscle, and any operation in this
      area should be performed with great caution.

PMID- 28428919
TI  - Tibial Bone Grafting for Wrist Reconstruction.
AB  - Background Iliac crest bone graft harvesting is routinely performed for upper
      extremity orthopedic procedures despite high complication rates associated with
      sensory nerve injury, hematoma, chronic pain, and fracture. Description of
      Technique Cancellous bone graft is harvested from the proximal tibia using a
      medial approach, minimizing donor site morbidity. Patients and Methods A
      retrospective review was undertaken of 14 patients who underwent cancellous
      proximal tibia bone graft harvesting to augment healing of wrist reconstruction,
      with 2 months minimum follow-up. We report donor limb tourniquet time, time to
      union, visual analog scale (VAS) pain score, and complications. Patients were
      also contacted by phone to administer a retrospective questionnaire and record
      experiences with the harvesting technique. Results Average donor site VAS for the
      immediate postoperative period was 7.4. Average tourniquet time was 28 minutes.
      Average time to union of the recipient site was 45 days. One patient experienced
      delayed union after corrective osteotomy, attributed to osteoporosis. Two
      patients underwent hardware removal from the operative wrist, unrelated to bone
      graft harvesting. One patient with a history of chronic neuropathy and foot drop
      developed dysesthesia and allodynia about the ipsilateral ankle, but was
      asymptomatic at the proximal tibia donor site; ankle symptoms resolved 3 weeks
      postoperatively. No patient reported any residual donor site difficulties 24.2
      months postoperatively. Conclusion In consideration of the minimal complication
      rate, favorable clinical parameters, and excellent patient tolerance, we advocate
      proximal tibia bone graft harvesting as opposed to iliac crest harvesting for
      wrist reconstruction when a moderate amount of autogenous cancellous graft is
      needed. Level of Evidence IV.

PMID- 28428920
TI  - Surgical Strategy and Techniques for Low-Profile Dorsal Plating in Treating
      Dorsally Displaced Unstable Distal Radius Fractures.
AB  - Background The low-profile dorsal locking plating (DLP) technique is useful for
      treating dorsally comminuted intra-articular distal radius fractures; however,
      due to the complications associated with DLP, the technique is not widely used.
      Methods A retrospective review of 24 consecutive cases treated with DLP were
      done. Results All cases were classified into two types by surgical strategy
      according to the fracture pattern. In type 1, there is a volar fracture line
      distal to the watershed line in the dorsally displaced fragment, and this type is
      treated by H-framed DLP. In type 2, the displaced dorsal die-punch fragment is
      associated with a minimally displaced styloid shearing fracture or a transverse
      volar fracture line. We found that the die-punch fragment was reduced by the
      buttress effect of small l-shaped DLP after stabilization of the styloid shearing
      for the volar segment by cannulated screws from radial styloid processes. At 6
      months after surgery, outcomes were good or excellent based on the modified Mayo
      wrist scores with no serious complications except one case. The mean range of
      motion of each type was as follows: the palmar flexion was 50, 65 degrees,
      dorsiflexion was 70, 75 degrees, supination was 85, 85 degrees, and pronation was
      80, 80 degrees; in type 1 and 2, respectively. Conclusion DLP is a useful
      technique for the treatment of selected cases of dorsally displaced, comminuted
      intra-articular fractures of the distal radius with careful soft tissue coverage.

PMID- 28428921
TI  - Distal Scaphoid Resection and Prosthetic Semireplacement Arthroplasty for a
      Scaphoid Nonunion with Degenerative Changes.

PMID- 28428922
TI  - The Cost-Benefit Balance of Statins in Hawai'i: A Moving Target.
AB  - Statins are lipid-lowering medications used for primary and secondary prevention
      of atherosclerotic disease and represent a substantial portion of drug costs in
      the United States. A better understanding of prescribing patterns and drug costs
      should lead to more rational utilization and help constrain health care
      expenditures in the United States. The 2013 Medicare Provider Utilization and
      Payment Data: Part D Prescriber Public Use File for the State of Hawai'i was
      analyzed. The number of prescriptions for statins, total annual cost, and daily
      cost were calculated by prescriber specialty and drug. Potential savings from
      substituting the highest-cost statin with lower-cost statins were calculated.
      Over 421,000 prescriptions for statins were provided to Medicare Part D
      beneficiaries in Hawai'i in 2013, which cost $17.6M. The three most commonly
      prescribed statins were simvastatin (33.4%), atorvastatin (33.4%), and lovastatin
      (13.9%). Although rosuvastatin comprised 5.4% of the total statin prescriptions,
      it represented 30.1% of the total cost of statins due to a higher daily cost
      ($5.53/day) compared to simvastatin ($0.25/day) and atorvastatin ($1.10/day).
      Cardiologists and general practitioners prescribed the highest percentage of
      rosuvastatin (8% each). Hypothetical substitution of rosuvastatin would have
      resulted in substantial annual cost savings (Simvastatin would have saved $1.3M
      for 25% substitution and $5.1M for 100% substitution, while atorvastatin would
      have saved $1.1M for 25% substitution and $4.3M for 100% substitution). Among
      Medicare Part D beneficiaries in Hawai'i, prescribing variation for statins
      between specialties were observed. Substitution of higher-cost with lower-cost
      statins may lead to substantial cost savings.

PMID- 28428923
TI  - The Long Term Outcome of the Management of the Posterior Capsule in Pseudophakic
      Children.
AB  - This is a long term study of the treatment of the posterior lens capsule in the
      management of bilateral cataract extraction and insertion of 42 intraocular
      lenses in 21 children. The purpose of the current study was to compare the long
      term outcome of eyes treated by the two different methods of surgery of the
      posterior lens capsule in bilateral cataract and intraocular lens implantation in
      children. The author performed an independent ocular exam on the children
      selected from a consecutive series at 4 different institutions, followed for a
      minimum of 5 years. The eyes of children in Subgroup A (n=24), had surgery in
      which an intact capsule was left at the time of initial surgery. The eyes of
      patients in Subgroup B (n=18) received a primary central lens capsulectomy and
      limited anterior vitrectomy at the time of the initial surgery. The eyes of
      Subgroup A (mean age 7.7 years) were found to be in children older than those
      eyes in Subgroup B (mean age 3.9 years) (P=.001). The eyes in the two subgroups
      also differed in the necessity of a secondary YAG laser capsulectomy. Twenty one
      of the 24 eyes in Subgroup A had received a secondary YAG laser capsulectomy and
      no eyes of the patients in Subgroup B had required a secondary YAG laser
      capsulectomy at the time of the author's examination (P=.001). A central
      capsulectomy during the initial surgery was more likely to be chosen for surgery
      on eyes of younger children (P=.001).

PMID- 28428924
TI  - A Case Report of Salmonella muenchen Enteritis Causing Rhabdomyolysis and
      Myocarditis in a Previously Healthy 26-Year-Old Man.
AB  - This case report examines an unusual presentation of a non-typhoidal Salmonella
      serovar with limited prevalence in the literature. This is the first case report
      to associate specifically the Salmonella muenchen serovar with rhabdomyolysis and
      myocarditis. This case report reviews the diagnostic criteria for myocarditis and
      explores the diagnostic dilemma of troponin elevation in the setting of
      rhabdomyolysis. It demonstrates that Salmonella muenchen has the ability to
      present in a broad range of individuals with complications extending beyond
      classical gastrointestinal symptoms. This report also concludes that diagnosis of
      the many possible complications from non-typhoidal Salmonella infections can be
      difficult due to patient comorbidities, variability in the severity of the
      illnesses, laboratory test limitations, and imaging limitations. When a patient
      presents with elevated troponins in the setting of rhabdomyolysis a careful
      workup should be done to evaluate for ischemic causes, myocarditis, or false
      elevation secondary to rhabdomyolysis.

PMID- 28428925
TI  - Medical School Hotline: Hawai'i Medical Education Program: An Innovative Method
      to Incorporate American Education Methodologies into the Traditional Japanese
      System.

PMID- 28428927
TI  - Limitations of Personalized Medicine and Gene Assays for Breast Cancer.
AB  - Adjuvant systemic treatments reduce the risk of breast cancer recurrence
      following the local treatment of primary stage I-III breast cancers. For patients
      with hormone-positive breast cancers receiving hormonal therapy, the risk of
      distant recurrence is under 20% and therefore, many patients may potentially be
      spared of chemotherapy. Consequently, several molecular signatures based on gene
      expression were developed to better determine which breast cancer patients would
      benefit from chemotherapy. We present the case of a 62-year-old woman diagnosed
      with an early stage hormone receptor-positive breast cancer that was treated with
      a partial mastectomy. Oncotype DX (Genomic Health, Redwood City, CA) molecular
      testing was performed on the surgical specimen, which reported a recurrence score
      of 0. The patient commenced adjuvant radiotherapy during which she developed
      symptoms suggestive of bone metastasis and was subsequently diagnosed with a
      spinal cord compression that required neurosurgery and radiotherapy. Pathology
      review of the specimen from the spine surgery revealed a metastatic breast
      carcinoma with neuroendocrine differentiation. Molecular assays such as Oncotype
      DX are increasingly used to prognosticate patient outcomes and help determine who
      may avoid chemotherapy. This case report seeks to illustrate that such assays
      should not be used in the presence of rare histological subtypes like
      neuroendocrine breast cancers, which are often under-reported. The current status
      of personalized medicine and gene assays in breast cancer is reviewed and
      potential strategies are suggested to identify these rare cases to better orient
      diagnostic and treatment decisions.

PMID- 28428928
TI  - Origin, Branching, and Communications of the Intercostobrachial Nerve: a Meta
      Analysis with Implications for Mastectomy and Axillary Lymph Node Dissection in
      Breast Cancer.
AB  - The intercostobrachial nerve (ICBN), which usually originates from the lateral
      cutaneous branch of the second intercostal nerve, innervates areas of the axilla,
      lateral chest, and medial arm. It is at risk for injury during operative
      procedures that are often used in the management of breast cancer and such injury
      has been associated with postoperative sensory loss and neuropathic pain,
      decreasing the quality of life. PubMed, Excerpta Medica Database (EMBASE),
      ScienceDirect, Google Scholar, China National Knowledge Infrastructure (CNKI),
      Scientific Electronic Library Online (SciELO), Biosciences Information Service
      (BIOSIS), and Web of Science were searched comprehensively. Data concerning the
      prevalence, branching, origin and communications of the ICBN were extracted and
      pooled into a meta-analysis. A total of 16 studies (1,567 axillas) reported data
      indicating that the ICBN was present in 98.4% of person. It most often (90.6%)
      originated from fibers at the T2 spinal level and commonly coursed in two
      branching patterns: as a single trunk in 47.0% of cases and as a bifurcating
      pattern in 42.2%. In the latter cases, the bifurcation was usually unequal
      (63.4%). Additionally, the ICBN presented with anastomosing communication to the
      brachial plexus in 41.3% of cases. The ICBN is a prevalent and variable structure
      at significant risk for injury during operative procedures of the axilla. In view
      of the postoperative pain and paresthesia experienced by patients following
      injury, surgeons need to exercise caution and aim to preserve the ICBN when
      possible. Ultimately, careful dissection and knowledge of ICBN anatomy could
      allow postoperative complications to be reduced and patient's quality of life
      increased.

PMID- 28428929
TI  - Treatment of Posttubercular Syringomyelia Not Responsive to Antitubercular
      Therapy: Case Report and Review of Literature.
AB  - Posttubercular adhesive arachnoiditis is a rare, late complication of tubercular
      meningitis. Syringomyelia can develop as a consequence of intramedullary cystic
      lesions and cerebrospinal fluid (CSF) flow disturbance around the spinal cord,
      even after successful chemotherapy. We reviewed the literature related to
      posttubercular syringomyelia treatment and suggest a new combined surgical
      approach. A 25-year-old Nigerian male patient presented with legs numbness,
      urinary disturbance, and legs weakness. Spinal magnetic resonance revealed a T5
      T7 syringomyelia, secondary to adhesive spinal arachnoiditis related to a history
      of tuberculous meningitis. Adhesiolysis by direct visualization with a flexible
      endoscope was performed and a handmade S-italic syringe-subdural shunt was placed
      to restore CSF flow. During the postoperative course, the neurological deficits
      improved together with the resolution of the syrinx. Long-term magnetic resonance
      imaging follow-up documented no recurrences or shunt displacements. We suggest
      that, when antitubercular therapy is not effective to resolve postarachnoiditis
      syrinx, arachnolysis with a flexible endoscope together with the placement of an
      S-italic shunt allowed free CSF communication between the syrinx and the
      subarachnoid space. Furthermore, we support that the use of an s-shaped shunt
      could prevent displacement or migration of the device and allows an easier
      revision in case of acute or late complications.

PMID- 28428930
TI  - Kidney disease and obesity paradox.

PMID- 28428931
TI  - The role of renal proximal tubule transport in the regulation of blood pressure.
AB  - The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral
      side of the renal proximal tubule plays a pivotal role in systemic acid-base
      homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal
      tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule
      reabsorbs most of the sodium filtered in the glomerulus, contributing to the
      regulation of plasma volume and blood pressure. NBCe1 and other sodium
      transporters in the proximal tubule are regulated by hormones, such as
      angiotensin II and insulin. Angiotensin II is probably the most important
      stimulator of sodium reabsorption. Proximal tubule AT1A receptor is crucial for
      the systemic pressor effect of angiotensin II. In rodents and rabbits, the effect
      on proximal tubule NBCe1 is biphasic; at low concentration, angiotensin II
      stimulates NBCe1 via PKC/cAMP/ERK, whereas at high concentration, it inhibits
      NBCe1 via NO/cGMP/cGKII. In contrast, in human proximal tubule, angiotensin II
      has a dose-dependent monophasic stimulatory effect via NO/cGMP/ERK. Insulin
      stimulates the proximal tubule sodium transport, which is IRS2-dependent. We
      found that in insulin resistance and overt diabetic nephropathy, stimulatory
      effect of insulin on proximal tubule transport was preserved. Our results suggest
      that the preserved stimulation of the proximal tubule enhances sodium
      reabsorption, contributing to the pathogenesis of hypertension with metabolic
      syndrome. We describe recent findings regarding the role of proximal tubule
      transport in the regulation of blood pressure, focusing on the effects of
      angiotensin II and insulin.

PMID- 28428932
TI  - A prime determinant in selecting dialysis modality: peritoneal dialysis patient
      survival.
AB  - The number of patients with end-stage renal disease (ESRD) has rapidly increased,
      as has the cost of dialysis. Peritoneal dialysis (PD) is an established treatment
      for ESRD patients worldwide; it has a variety of advantages, including autonomy
      and flexibility, as well as economic benefits in many countries compared to
      hemodialysis (HD). However, the long-term survival rate of PD remains poor.
      Although direct comparison of survival rate between the dialysis modalities by
      randomized controlled trials is difficult due to the ethical issues, it has
      always been a crucial point when deciding which dialysis modality should be
      recommended to patients. Recently, in many countries, including the United
      States, Brazil, Spain, Australia, and New Zealand, the survival rate in PD
      patients has significantly improved. PD patient survival in Korea has also
      improved, but Korean PD patients are known to have higher risk of mortality and
      major adverse cardiovascular, cerebrovascular events than HD patients. Herein, we
      further evaluate why Korean PD patients had worse outcomes; we suggest that
      special attention should be paid to patients with diabetes, coronary artery
      disease, or congestive heart failure when they choose PD as the first dialysis
      modality in order to reduce mortality risk.

PMID- 28428933
TI  - Cardiac arrest caused by nafamostat mesilate: Kounis syndrome in the dialysis
      room?

PMID- 28428934
TI  - The authors' reply.

PMID- 28428935
TI  - Genetic Analysis of Mosquito Detection of Humans.
AB  - Mosquitoes detect the presence of humans by integrating chemosensory, thermal,
      and visual cues. Among these, odors are crucial for mosquito host detection.
      Insects have evolved a diverse repertoire of receptors to detect their plant and
      animal hosts. Genetic analysis of these receptors in Drosophila has set the stage
      for similar studies in mosquitoes. The diversity of the cues involved in mosquito
      host-seeking has made designing behavioral control strategies a challenge. The
      sensory receptors that are most important for mosquito detection of humans can
      now be determined using genome editing. Here, we will review our current
      understanding of the salient cues that attract mosquitoes, their receptors, and
      suggest ways forward for novel olfaction-based vector control strategies.

PMID- 28428936
TI  - Multistate Models on Pleural Effusion after Allogeneic Hematopoietic Stem Cell
      Transplantation.
AB  - A multistate model is more complicated than competing risk models and composed of
      finite number of states and transitions between states. Unlike competing risk
      models, this model has the ability to assess the effect of occurrence order of
      time-to-event data. Pleural effusion (PE) is a severe complication that often
      occurs after allogeneic hematopoietic stem cell transplantation (HSCT). Many
      patients develop pleural effusion during the first 100 days after allogeneic HSCT
      and graft-versus-host disease (GVHD) occurs either before or after the
      development of PE, implying that the occurrence order of PE and GVHD (i.e., PE
      after GVHD vs. GVHD after PE) would influence on the incidence, risk factors and
      mortality of pleural effusion. One can use either Cox proportional models or
      competing risk models to evaluate these values, but neither method is able to
      incorporate the occurrence order of incidence into the model. To resolve this
      difficulty, we developed a multistate model describing several possible events
      and event-related dependences and applied to a retrospective study of 606
      patients, including eight covariates.

PMID- 28428938
TI  - Effects of supplementation with antifreeze proteins on the follicular integrity
      of vitrified-warmed mouse ovaries: Comparison of two types of antifreeze proteins
      alone and in combination.
AB  - OBJECTIVE: The aim of this study was to analyze the effect of supplementing
      vitrification and warming solutions with two types of antifreeze proteins (AFPs)
      and the combination thereof on the follicular integrity of vitrified-warmed mouse
      ovaries. METHODS: Ovaries (n=154) were obtained from 5-week-old BDF1 female mice
      (n=77) and vitrified using ethylene glycol and dimethyl sulfoxide with the
      supplementation of 10 mg/mL of Flavobacterium frigoris ice-binding protein
      (FfIBP), 10 mg/mL of type III AFP, or the combination thereof. Ovarian sections
      were examined by light microscopy after hematoxylin and eosin staining, and
      follicular intactness was assessed as a whole and according to the type of
      follicle. Apoptosis within the follicles as a whole was detected by a terminal
      deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay.
      RESULTS: The proportion of overall intact follicles was significantly higher in
      the type III AFP-supplemented group (60.5%) and the combination group (62.9%)
      than in the non-supplemented controls (43.8%, p<0.05 for each). The proportion of
      intact primordial follicles was significantly higher in the FfIBP-supplemented
      (90.0%), type III AFP-supplemented (92.3%), and combination (89.7%) groups than
      in the non-supplemented control group (46.2%, p<0.05 for each). The proportions
      of non-apoptotic follicles were similar across the four groups. CONCLUSION:
      Supplementation of the vitrification and warming solutions with FfIBP, type III
      AFP, or the combination thereof was equally beneficial for the preservation of
      primordial follicles in vitrified mouse ovaries.

PMID- 28428937
TI  - Intravenous immunoglobulin G in women with reproductive failure: The Korean
      Society for Reproductive Immunology practice guidelines.
AB  - The task force of the Korean Society for Reproductive Immunology recommends
      intravenous immunoglobulin G treatment in women with reproductive failure,
      including recurrent pregnancy loss and/or repeated implantation failure, who show
      cellular immune factors such as abnormal natural killer cell levels, natural
      killer cell cytotoxicity, and/or type 1 T helper immunity.

PMID- 28428939
TI  - Effects of sperm insemination on the final meiotic maturation of mouse oocytes
      arrested at metaphase I after in vitro maturation.
AB  - OBJECTIVE: The aims of this study were to investigate whether fertilization could
      induce the resumption of meiosis in mouse oocytes arrested at metaphase I (MI)
      after in vitro maturation (IVM), and to investigate the effect of Ca2+ chelator
      treatment at the time of fertilization on the transition from MI to metaphase II
      (MII). METHODS: MII-stage and arrested MI-stage mouse oocytes after IVM were
      fertilized, and then embryonic development was monitored. Blastocysts from each
      group were transferred into 2.5 days post-coitum pseudo-pregnant ICR mice. MI
      oocytes after IVM were treated with a Ca2+ chelator to investigate the effect of
      Ca2+ oscillations on their maturation. RESULTS: As insemination time increased,
      the number of oocytes in the MI group that reached the MII stage also increased.
      The blastocyst rates and total cell numbers in the MII group were significantly
      higher than in the MI group. No pregnancy occurred in the MI group, but 10
      pregnancies were achieved (10 of 12) in the MII group. The proportion of MI
      oocytes that matured to MII oocytes after fertilization was significantly higher
      in the non-treated group than in the Ca2+ chelator-treated group. CONCLUSION: The
      findings that a higher proportion of MI-arrested oocytes progressed to MII after
      fertilization and that the MI-to-MII transition was blocked by Ca2+ chelator
      treatments before fertilization indicate that the maturation of MI oocytes to MII
      oocytes is associated with intracellular Ca2+ oscillations driven by
      fertilization.

PMID- 28428940
TI  - Factors influencing sperm retrieval following testicular sperm extraction in
      nonobstructive azoospermia patients.
AB  - OBJECTIVE: Azoospermia owing to testicular disorders is the most severe
      manifestation of male infertility. The main concern for patients with
      nonobstructive azoospermia (NOA) is the probability of successful sperm retrieval
      following testicular sperm extraction (TESE). Therefore, the goal of this study
      was to determine predictive factors correlated with sperm retrieval. METHODS: We
      assessed the testicular histopathological patterns, the choice of TESE surgical
      procedure, hormone levels, and chromosomal abnormalities in patients with NOA
      (n=170). The histopathology specimens were analyzed based on the
      histopathological patterns of hypospermatogenesis, maturation arrest, and Sertoli
      cell-only syndrome. RESULTS: The mean rate of sperm retrieval was 48.8%. The rate
      of sperm retrieval was significantly higher in the hypospermatogenesis group than
      in the other groups (p<0.001). There was a positive correlation between micro
      TESE (vs. conventional TESE) and the sperm retrieval rate (odds ratio, 8.077;
      p<0.01). A logistic regression model demonstrated that high levels of follicle
      stimulating hormone (FSH) and small testicular volume were significantly
      associated with lower chances of successful sperm retrieval. CONCLUSION: Some
      parameters, including testicular histopathology patterns, FSH levels, testicular
      volume, and method of TESE surgery, may be able to predict the chances of
      obtaining spermatozoa in patients with NOA. However, despite the efficiency of
      some predictive models, the hope of retrieving any functioning spermatozoa may be
      sufficient to disregard predictive factors of the success of intracytoplasmic
      sperm injection in these patients.

PMID- 28428941
TI  - Cardiovascular risk may be increased in women with unexplained infertility.
AB  - OBJECTIVE: Growing evidence suggests that increased cardiovascular disease (CVD)
      risk is associated with female infertility caused by conditions such as
      polycystic ovarian disease, obesity, thyroid dysfunction, and endometriosis. The
      aim of this study was to evaluate whether any relationship exists between CVD and
      unexplained infertility. METHODS: Sixty-five women with unexplained infertility
      and 65 fertile controls were enrolled in the study. CVD risk markers such as low
      density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol
      (TC), triglycerides (TG), insulin resistance (defined by the homeostasis model
      assessment ratio), and high-sensitivity C-reactive protein (hs-CRP) were
      assessed. RESULTS: TG, TC, LDL, and hs-CRP levels were higher and HDL levels were
      lower in patients with unexplained infertility than in fertile controls (p<0.05
      for all). Positive associations were found between unexplained infertility and
      TG, TC, LDL, and hs-CRP levels, and a negative correlation was found for HDL
      (p<0.05 for all). Multivariate logistic regression analysis showed that TG, HDL,
      and hs-CRP were independent variables associated with unexplained infertility.
      CONCLUSION: Our study showed that women with unexplained infertility had an
      atherogenic lipid profile and elevated hs-CRP levels, suggesting a higher risk of
      developing CVD in the future. Further studies with larger groups are needed to
      investigate the nature of this link.

PMID- 28428942
TI  - Follicular fluid cerebellin and betatrophin regulate the metabolic functions of
      growing follicles in polycystic ovary syndrome.
AB  - OBJECTIVE: The aim of this study was to assess the changes of follicular fluid
      (FF) and serum levels of cerebellin precursor protein 1 (cbln1) and betatrophin
      in patients with polycystic ovary syndrome (PCOS) undergoing in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) with a gonadotropin
      releasing hormone (GnRH) antagonist protocol. METHODS: Twenty infertile women
      with PCOS and 20 control women diagnosed as poor responders undergoing ovarian
      stimulation with a GnRH antagonist were included. Blood samples were obtained
      during ovum pick-up. Follicular fluid from a dominant follicle was collected from
      the subjects. Using enzyme-linked immunosorbent assays, FF and serum levels of
      cbln1 and betatrophin were measured in both groups of participants. Metabolic and
      hormonal parameters were also determined and correlated with each other. RESULTS:
      Both groups of women had similar serum and FF betatrophin levels (55.0+/-8.9
      ng/mL vs. 53.1+/-10.3 ng/mL, p=0.11). The serum and FF betatrophin levels of poor
      responders were found to be similar (49.9+/-5.9 ng/mL vs. 48.9+/-10.7 ng/mL,
      p=0.22). Conversely, the FF cbln1 levels of PCOS women were found to be
      significantly higher than the serum cbln1 levels (589.1+/-147.6 ng/L vs. 531.7+/
      74.3 ng/L, p<0.02). The FF cbln1 levels of control participants without PCOS were
      significantly higher than their serum cbln1 levels (599.3+/-211.5 ng/L vs.
      525.3+/-87.0 ng/L, p=0.01). Positive correlations were detected among body mass
      index, insulin resistance, serum insulin, total testosterone, and betatrophin
      levels in the PCOS group. CONCLUSION: Follicular fluid betatrophin and cbln1
      concentrations may play a pivotal role on follicular growth in PCOS subjects
      undergoing IVF/ICSI with an antagonist protocol.

PMID- 28428943
TI  - Pathogenic variant in NLRP7 (19q13.42) associated with recurrent gestational
      trophoblastic disease: Data from early embryo development observed during in
      vitro fertilization.
AB  - OBJECTIVE: To describe in vitro development of human embryos derived from an
      individual with a homozygous pathogenic variant in NLRP7 (19q13.42) and recurrent
      hydatidiform mole (HM), an autosomal recessive condition thought to occur
      secondary to an oocyte defect. METHODS: A patient with five consecutive HM
      pregnancies was genomically evaluated via next generation sequencing followed by
      controlled ovarian hyperstimulation, in vitro fertilization (IVF) with
      intracytoplasmic sperm injection, embryo culture, and preimplantation genetic
      screening. Findings in NLRP7 were recorded and embryo culture and biopsy data
      were tabulated as a function of parental origin for any identified ploidy error.
      RESULTS: The patient was found to have a pathogenic variant in NLRP7
      (c.2810+2T>G) in a homozygous state. Fifteen oocytes were retrieved and 10
      embryos were available after fertilization via intracytoplasmic sperm injection.
      Developmental arrest was noted for all 10 embryos after 144 hours in culture,
      thus no transfer was possible. These non-viable embryos were evaluated by
      karyomapping and all were diploid biparental; two were euploid and eight had
      various aneuploidies all of maternal origin. CONCLUSION: This is the first report
      of early human embryo development from a patient with any NLRP7 mutation. The
      pathogenic variant identified here resulted in global developmental arrest at or
      before blastocyst stage. Standard IVF should therefore be discouraged for such
      patients, who instead need to consider oocyte (or embryo) donation with IVF as
      preferred clinical methods to treat infertility.

PMID- 28428944
TI  - The status of assisted reproductive technology in Korea in 2012.
AB  - OBJECTIVE: This study was designed to report the status of assisted reproductive
      technology (ART) therapy in South Korea between January 1, 2012 and December 31,
      2012. METHODS: A localized online survey, originally developed by the
      International Committee Monitoring Assisted Reproductive Technologies, was first
      launched and provided to all available ART centers via email in 2015. Fresh
      embryo transfer (FET) cases were categorized as standard in vitro fertilization,
      intracytoplasmic sperm injection (ICSI), or half-ICSI. Thawed embryo transfer
      (TET) and other related procedures, including surgical sperm retrieval, were
      surveyed. RESULTS: Data from 33,956 ovum pick-up procedures were provided by 75
      clinics in 2012. Of the 33,088 cycles in which ovums were retrieved, a complete
      transfer was performed in 90.5% (29,932 cycles). In addition, 10,079 FET cycles
      were confirmed to have resulted in clinical pregnancy, representing a pregnancy
      rate of 30.5% per ovum pick-up and 33.7% per ET. The most common number of
      embryos transferred in FET was 2 (41.6%), followed by 3 (34.0%), and non-elective
      single ETs (10.0%). Of the 10,404 TET cycles in which transfer was completed,
      3,760 clinical pregnancies (36.1%) were confirmed by ultrasonography. CONCLUSION:
      The overall clinical pregnancy rate for FET and TET cycles in 2012 was higher
      than in 2011 (33.7% vs. 33.2% and 36.1% vs. 31.1%, respectively). The most common
      number of embryos transferred in FET cycles was 2, unlike in 2011.

PMID- 28428945
TI  - A successful pregnancy using completely immotile but viable frozen-thawed
      spermatozoa selected by laser.
AB  - The aim of this study was to report a successful pregnancy using completely
      immotile frozen-thawed spermatozoa selected by laser. A single laser shot was
      used to detect the presence of viable immotile spermatozoa in fresh and frozen
      thawed testicular spermatozoa. The viability rate was 55.8% after the laser
      detection, and cryopreservation was carried out immediately. The thawing test was
      performed on the day of oocyte pick-up, and no motile sperm were observed after
      extending the culture for another 4 hours, while a survival rate of 39.8% was
      detected using the laser. In all, five mature oocytes were injected, resulting in
      four cases of normal fertilization (80%) on day 1. Further, two high-quality day
      3 embryos were transferred, which resulted in a singleton pregnancy. Our study
      demonstrates that completely immotile spermatozoa are worth cryopreserving for
      further intracytoplasmic sperm injection, which provides a new insight into male
      fertility preservation in cases of completely immotile spermatozoa.

PMID- 28428946
TI  - Acknowledgment to reviewers for 2016.

PMID- 28428947
TI  - Update on Programmed Death-1 and Programmed Death-Ligand 1 Inhibition in the
      Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer.
AB  - PURPOSE: Non-small-cell lung cancer (NSCLC) has a large worldwide prevalence with
      a high mortality rate. Chemotherapy has offered modest improvements in survival
      over the past two decades. Immune checkpoint modulation with programmed death-1
      (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has shown the promise of
      changing the future landscape of cancer therapy. This update reviews recent
      advances in the treatment of NSCLC with immune checkpoint modulation. METHODS:
      Publications and proceedings were identified from searching PubMed and
      proceedings from the annual meetings of the American Society of Clinical
      Oncology, European Society for Medical Oncology, and European Lung Cancer
      Conference. RESULTS: Atezolizumab, nivolumab, and pembrolizumab increase overall
      survival in second-line treatment of Stage III/IV squamous and non-squamous NSCLC
      when compared to docetaxel. Pembrolizumab increases progression-free survival in
      the first-line treatment of Stage IV NSCLC with 50% PD-L1 expression when
      compared to platinum-based chemotherapy. Combination therapy with chemotherapy
      and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors has shown
      promise in early trials. CONCLUSION: Immune checkpoint modulation produces
      durable responses and overall survival benefits with less toxicity compared to
      conventional chemotherapy. Future investigations are combining PD-1/L1 inhibition
      with chemotherapy, targeted therapy, or other immuno-oncology agents in an effort
      to further improve efficacy.

PMID- 28428948
TI  - Understanding the Entanglement: Neutrophil Extracellular Traps (NETs) in Cystic
      Fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in
      the gene that codes for the CF trans-membrane conductance regulator. These
      mutations result in abnormal secretions viscous airways of the lungs, favoring
      pulmonary infection and inflammation in the middle of neutrophil recruitment.
      Recently it was described that neutrophils can contribute with disease pathology
      by extruding large amounts of nuclear material through a mechanism of cell death
      known as Neutrophil Extracellular Traps (NETs) into the airways of patients with
      CF. Additionally, NETs production can contribute to airway colonization with
      bacteria, since they are the microorganisms most frequently found in these
      patients. In this review, we will discuss the implication of individual or mixed
      bacterial infections that most often colonize the lung of patients with CF, and
      the NETs role on the disease.

PMID- 28428949
TI  - P2X1, P2X4, and P2X7 Receptor Knock Out Mice Expose Differential Outcome of
      Sepsis Induced by alpha-Haemolysin Producing Escherichia coli.
AB  - alpha-haemolysin (HlyA)-producing Escherichia coli commonly inflict severe
      urinary tract infections, including pyelonephritis, which comprises substantial
      risk for sepsis. In vitro, the cytolytic effect of HlyA is mainly mediated by ATP
      release through the HlyA pore and subsequent P2X1/P2X7 receptor activation. This
      amplification of the lytic process is not unique to HlyA but is observed by many
      other pore-forming proteins including complement-induced haemolysis. Since free
      hemoglobin in the blood is known to be associated with a worse outcome in sepsis
      one could speculate that inhibition of P2X receptors would ameliorate the course
      of sepsis. Surprisingly, this study demonstrates that [Formula: see text] and
      [Formula: see text] mice are exceedingly sensitive to sepsis with uropathogenic
      E. coli. These mice have markedly lower survival, higher cytokine levels and
      activated intravascular coagulation. Quite the reverse is seen in [Formula: see
      text] mice, which had markedly lower cytokine levels and less coagulation
      activation compared to controls after exposure to uropathogenic E. coli. The high
      cytokine levels in the [Formula: see text] mouse are unexpected, since P2X7 is
      implicated in caspase-1-dependent IL-1beta production. Here, we demonstrate that
      IL-1beta production during sepsis with uropathogenic E. coli is mediated by
      caspase-8, since caspase-8 and RIPK3 double knock out mice show substantially
      lower cytokine during sepsis and increased survival after injection of TNFalpha.
      These data support that P2X7 and P2X4 receptor activation has a protective effect
      during severe E. coli infection.

PMID- 28428951
TI  - The effect of flour from the rind of the yellow passion fruit on glycemic control
      of people with diabetes mellitus type 2: a randomized clinical trial.
AB  - BACKGROUND: The single or combined use of herbal and dietary products with
      medications has shown benefits in the metabolic modulation of carbohydrates, in
      the restoring of the function of pancreatic beta cells, and in insulin
      resistance. To analyze the effect of the use of flour made from the rind of the
      yellow passion fruit on the glycemic control of people with diabetes mellitus
      type 2. METHODS: An open, prospective, randomized clinical trial was undertaken
      with 54 participants over an eight-week period. The participants from the case
      group were advised to ingest 12 g of the flour, three times daily; before
      breakfast, lunch and dinner. RESULTS: After eight weeks of use of the flour made
      from the rind of the yellow passion fruit, we did not identify significant
      statistical differences in the values for capillary blood glucose (p = 0.562),
      fasting blood glucose (p = 0.268) or glycated hemoglobin (p = 0.229) between the
      study groups. In the case group, we identified an increase (29.6%-37%) of the
      people with normal HbA1c; however, this did not have statistical relevance (p =
      0.274). DISCUSSION: Based in our findings, we believe it is important to extend
      the time of exposure to the intervention and increase the rigor in the monitoring
      of adherence in future studies on this topic. Only in this way will we be able to
      make confident inferences in relation to the use of flour made from the rind of
      theyellow passion fruit as a therapeutic tool for glycemic and/or metabolic
      control in persons with DM 2. CONCLUSIONS: In the sample in question, the use of
      the flour made from the rind of the yellow passion fruit, over an eight-week
      period, did not improve the glycemic control of people with type 2 diabetes.
      Trial registration: U1111.1187.3616. Registered 6 September, retrospectively
      registered, in the Brazilian Clinical Trials Registry.

PMID- 28428950
TI  - Endogenous and Exogenous KdpF Peptide Increases Susceptibility of Mycobacterium
      bovis BCG to Nitrosative Stress and Reduces Intramacrophage Replication.
AB  - Emerging antibiotic resistance in pathogenic bacteria like Mycobacterium sp.,
      poses a threat to human health and therefore calls for the development of novel
      antibacterial strategies. We have recently discovered that bacterial membrane
      peptides, such as KdpF, possess anti-virulence properties when overproduced in
      pathogenic bacterial species. Overproduction of the KdpF peptide in Mycobacterium
      bovis BCG decreased bacterial replication within macrophages, without presenting
      antibacterial activity. We propose that KdpF functions as a regulatory molecule
      and interferes with bacterial virulence, potentially through interaction with the
      PDIM transporter MmpL7. We demonstrate here that KdpF overproduction in M. bovis
      BCG, increased bacterial susceptibility to nitrosative stress and thereby was
      responsible for lower replication rate within macrophages. Moreover, in a
      bacterial two-hybrid system, KdpF was able to interact not only with MmpL7 but
      also with two membrane proteins involved in nitrosative stress detoxification
      (NarI and NarK2), and a membrane protein of unknown function that is highly
      induced upon nitrosative stress (Rv2617c). Interestingly, we showed that the
      exogenous addition of KdpF synthetic peptide could affect the stability of
      proteins that interact with this peptide. Finally, the exogenous KdpF peptide
      presented similar biological effects as the endogenously expressed peptide
      including nitrosative stress susceptibility and reduced intramacrophage
      replication rate for M. bovis BCG. Taken together, our results establish a link
      between high levels of KdpF and nitrosative stress susceptibility to further
      highlight KdpF as a potent molecule with anti-virulence properties.

PMID- 28428952
TI  - Usefulness and capability of three-dimensional, full high-definition movies for
      surgical education.
AB  - BACKGROUND: Because of changing surgical procedures in the fields of oral and
      maxillofacial surgery, new methods for surgical education are needed and could
      include recent advances in digital technology. Many doctors have attempted to use
      digital technology as educational tools for surgical training, and movies have
      played an important role in these attempts. We have been using a 3D full high
      definition (full-HD) camcorder to record movies of intra-oral surgeries. METHOD:
      The subjects were medical students and doctors receiving surgical training who
      did not have actual surgical experience (n = 67). Participants watched an 8-min,
      2D movie of orthognathic surgery and subsequently watched the 3D version. After
      watching the 3D movie, participants were asked to complete a questionnaire.
      RESULT: A lot of participants (84%) felt a 3D movie excellent or good and
      answered that the advantages of a 3D movie were their appearance of solidity or
      realism. Almost all participants (99%) answered that 3D movies were quite useful
      or useful for medical practice. CONCLUSIONS: Three-dimensional full-HD movies
      have the potential to improve the quality of medical education and clinical
      practice in oral and maxillofacial surgery.

PMID- 28428954
TI  - Uncovering the Roles of Septins in Cilia.
AB  - Septins are a family of GTP-binding proteins that associate with cellular
      membranes and the cytoskeleton. Their ability to polymerize into filamentous
      structures permits them to serve as diffusion barriers for membrane proteins and
      as multi-molecular scaffolds that recruit components of signaling pathways. At
      the cellular level, septins contribute to the regulation of numerous processes,
      including cytokinesis, cell polarity, cell migration, and many others. In this
      review, we discuss emerging evidence for roles of mammalian septins in the
      biogenesis and function of flagella and cilia, and how this may impact human
      diseases such as ciliopathies.

PMID- 28428953
TI  - Tetraspanins Function as Regulators of Cellular Signaling.
AB  - Tetraspanins are molecular scaffolds that distribute proteins into highly
      organized microdomains consisting of adhesion, signaling, and adaptor proteins.
      Many reports have identified interactions between tetraspanins and signaling
      molecules, finding unique downstream cellular consequences. In this review, we
      will explore these interactions as well as the specific cellular responses to
      signal activation, focusing on tetraspanin regulation of adhesion-mediated
      (integrins/FAK), receptor-mediated (EGFR, TNF-alpha, c-Met, c-Kit), and
      intracellular signaling (PKC, PI4K, beta-catenin). Additionally, we will
      summarize our current understanding for how tetraspanin post-translational
      modifications (palmitoylation, N-linked glycosylation, and ubiquitination) can
      regulate signal propagation. Many of the studies outlined in this review suggest
      that tetraspanins offer a potential therapeutic target to modulate aberrant
      signal transduction pathways that directly impact a host of cellular behaviors
      and disease states.

PMID- 28428955
TI  - Commentary: A Breathing-Based Meditation Intervention for Patients with Major
      Depressive Disorder Following Inadequate Response to Antidepressants: A
      Randomized Pilot Study.

PMID- 28428958
TI  - Debromoaplysiatoxin as the Causative Agent of Dermatitis in a Dog after Exposure
      to Freshwater in California.
AB  - Contamination of recreational waters with cyanobacterial toxins continues to
      increase and presents a risk to animals and humans. Although cases of acute
      hepato- and neurotoxicoses in dogs following cyanotoxin exposure exist, no
      reports of skin-related reactions in dogs exist. A 5-year-old female spayed 34 kg
      Bracco Italiano was initially presented for rapid onset of severe pruritus and
      urticaria. Marked excoriation and erythema were noted over the chest and neck,
      while urticaria was noted in the inguinal regions and ventral abdomen. Initial
      basic dermatology work-up excluded parasitic, fungal, and bacterial organisms.
      Due to the severity and progression of urticaria, the dog received IV
      dexamethasone and IM diphenhydramine. Improvement of the urticaria and the dog's
      clinical status was noted over the next 45 min. Assessment of the dog's
      environment revealed access to a lake on the property with visible algal bloom.
      Water from the lake was submitted for toxicology testing and revealed the
      presence of debromoaplysiatoxin. Access to the lake was discontinued and follow
      up evaluation over the next few weeks revealed a complete resolution of the skin
      irritation. To the authors' knowledge, this is the first case report of
      debromoaplysiatoxin exposure in a dog after swimming in cyanobacteria
      contaminated water. Veterinarians should recognize the potential harm that
      contaminated waters may cause in terms of dermal, hepatic, and neurological
      conditions. In addition, more prudent oversight of contaminated recreational
      waters is recommended for animals and humans to prevent adverse events and
      intoxications.

PMID- 28428957
TI  - Coordinating Regulation of Gene Expression in Cardiovascular Disease:
      Interactions between Chromatin Modifiers and Transcription Factors.
AB  - Cardiovascular disease is a leading cause of death with increasing economic
      burden. The pathogenesis of cardiovascular diseases is complex, but can arise
      from genetic and/or environmental risk factors. This can lead to dysregulated
      gene expression in numerous cell types including cardiomyocytes, endothelial
      cells, vascular smooth muscle cells, and inflammatory cells. While initial
      studies addressed transcriptional control of gene expression, epigenetics has
      been increasingly appreciated to also play an important role in this process
      through alterations in chromatin structure and gene accessibility. Chromatin
      modifying proteins including enzymes that modulate DNA methylation, histone
      methylation, and histone acetylation can influence gene expression in numerous
      ways. These chromatin modifiers and their marks can promote or prevent
      transcription factor recruitment to regulatory regions of genes through
      modifications to DNA, histones, or the transcription factors themselves. This
      review will focus on the emerging question of how epigenetic modifiers and
      transcription factors interact to coordinately regulate gene expression in
      cardiovascular disease. While most studies have addressed the roles of either
      epigenetic or transcriptional control, our understanding of the integration of
      these processes is only just beginning. Interrogating these interactions is
      challenging, and improved technical approaches will be needed to fully dissect
      the temporal and spatial relationships between transcription factors, chromatin
      modifiers, and gene expression in cardiovascular disease. We summarize the
      current state of the field and provide perspectives on limitations and future
      directions. Through studies of epigenetic and transcriptional interactions, we
      can advance our understanding of the basic mechanisms of cardiovascular disease
      pathogenesis to develop novel therapeutics.

PMID- 28428959
TI  - Copy Number Variations in Candidate Genes and Intergenic Regions Affect Body Mass
      Index and Abdominal Obesity in Mexican Children.
AB  - Introduction. Increase in body weight is a gradual process that usually begins in
      childhood and in adolescence as a result of multiple interactions among
      environmental and genetic factors. This study aimed to analyze the relationship
      between copy number variants (CNVs) in five genes and four intergenic regions
      with obesity in Mexican children. Methods. We studied 1423 children aged 6-12
      years. Anthropometric measurements and blood levels of biochemical parameters
      were obtained. Identification of CNVs was performed by real-time PCR. The effect
      of CNVs on obesity or body composition was assessed using regression models
      adjusted for age, gender, and family history of obesity. Results. Gains in copy
      numbers of LEPR and NEGR1 were associated with decreased body mass index (BMI),
      waist circumference (WC), and risk of abdominal obesity, whereas gain in ARHGEF4
      and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d and losses
      in INS were associated with increased BMI and WC. Conclusion. Our results
      indicate a possible contribution of CNVs in LEPR, NEGR1, ARHGEF4, and CPXCR1 and
      the intergenic regions 12q15c, 15q21.1a, and 22q11.21d to the development of
      obesity, particularly abdominal obesity in Mexican children.

PMID- 28428960
TI  - MicroRNA and Cardiovascular Disease 2016.

PMID- 28428961
TI  - Glucose-Insulin-Potassium Alleviates Intestinal Mucosal Barrier Injuries
      Involving Decreased Expression of Uncoupling Protein 2 and NLR Family-Pyrin
      Domain-Containing 3 Inflammasome in Polymicrobial Sepsis.
AB  - Uncoupling protein 2 (UCP2) may be critical for intestinal barrier function which
      may play a key role in the development of sepsis, and insulin has been reported
      to have anti-inflammatory effects. Male Sprague-Dawley rats were randomly
      allocated into five groups: control group, cecal ligation and puncture (CLP)
      group, sham surgery group, CLP plus glucose-insulin-potassium (GIK) group, and
      CLP plus glucose and potassium (GK) group. Ileum tissues were collected at 24 h
      after surgery. Histological and cytokine analyses, intestinal permeability tests,
      and western blots of intestinal epithelial tight junction component proteins and
      UCP2 were performed. Compared with CLP group, the CLP + GIK group had milder
      histological damage, lower levels of cytokines in the serum and ileum tissue
      samples, and lower UCP2 expression, whereas the CLP + GK group had no such
      effects. Moreover, the CLP + GIK group exhibited decreased epithelial
      permeability of the ileum and increased expression of zonula occludens-1,
      occludin, and claudin-1 in the ileum. The findings demonstrated that the UCP2 and
      NLR family-pyrin domain-containing 3/caspase 1/interleukin 1beta signaling
      pathway may be involved in intestinal barrier injury and that GIK treatment
      decreased intestinal barrier permeability. Thus, GIK may be a useful treatment
      for intestinal barrier injury during sepsis.

PMID- 28428956
TI  - Physiological Functions of the Cellular Prion Protein.
AB  - The prion protein, PrPC, is a small, cell-surface glycoprotein notable primarily
      for its critical role in pathogenesis of the neurodegenerative disorders known as
      prion diseases. A hallmark of prion diseases is the conversion of PrPC into an
      abnormally folded isoform, which provides a template for further pathogenic
      conversion of PrPC, allowing disease to spread from cell to cell and, in some
      circumstances, to transfer to a new host. In addition to the putative
      neurotoxicity caused by the misfolded form(s), loss of normal PrPC function could
      be an integral part of the neurodegenerative processes and, consequently,
      significant research efforts have been directed toward determining the
      physiological functions of PrPC. In this review, we first summarise important
      aspects of the biochemistry of PrPC before moving on to address the current
      understanding of the various proposed functions of the protein, including details
      of the underlying molecular mechanisms potentially involved in these functions.
      Over years of study, PrPC has been associated with a wide array of different
      cellular processes and many interacting partners have been suggested. However,
      recent studies have cast doubt on the previously well-established links between
      PrPC and processes such as stress-protection, copper homeostasis and neuronal
      excitability. Instead, the functions best-supported by the current literature
      include regulation of myelin maintenance and of processes linked to cellular
      differentiation, including proliferation, adhesion, and control of cell
      morphology. Intriguing connections have also been made between PrPC and the
      modulation of circadian rhythm, glucose homeostasis, immune function and cellular
      iron uptake, all of which warrant further investigation.

PMID- 28428962
TI  - A Higher Ovarian Response after Stimulation for IVF Is Related to a Higher Number
      of Euploid Embryos.
AB  - This study has analysed the relationship between ovarian response and the number
      of euploid embryos. This is a post hoc analysis of a subset of data generated
      during a prospective cohort study previously published. Forty-six oocyte donors
      were subjected to ovarian stimulation with 150 IU of rFSH and 75 IU of hp-hMG in
      a GnRH agonist long protocol. Preimplantation genetic screening was performed in
      all viable embryos. We observed a positive relationship between ovarian response
      and the number of euploid embryos. When ovarian response was above the median
      (>=17 oocytes), the mean number of euploid embryos per donor was 5.0 +/- 2.4,
      while when <17 oocytes were obtained the mean number of euploid embryos was 2.7
      +/- 1.4 (p = 0.000). Aneuploidy rate did not increase with ovarian response or
      gonadotropin doses. Also, the number of euploid embryos was inversely related to
      the amount of gonadotropins needed per oocyte obtained (ovarian sensitivity
      index). These results suggest that the number of euploid embryos available for
      embryo transfer increases as the number of oocytes obtained does. Considering the
      total number of euploid embryos seems more relevant than the aneuploidy rate.

PMID- 28428963
TI  - Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation
      Possibly by Akt and Erk1/2 Pathways.
AB  - This study aimed to investigate the effects and mechanisms of quercetin on
      pulmonary arterial endothelial cell (PAEC) transdifferentiation into smooth
      muscle-like cells. TGF-beta1-induced PAEC transdifferentiation models were
      applied to evaluate the pharmacological actions of quercetin. PAEC proliferation
      was detected with CCK8 method and BurdU immunocytochemistry. Meanwhile, the
      identification and transdifferentiation of PAECs were determined by FVIII
      immunofluorescence staining and alpha-SMA protein expression. The related
      mechanism was elucidated based on the levels of Akt and Erk1/2 signal pathways.
      As a result, quercetin effectively inhibited the TGF-beta1-induced proliferation
      and transdifferentiation of the PAECs and activation of Akt/Erk1/2 cascade in the
      cells. In conclusion, quercetin is demonstrated to be effective for pulmonary
      arterial hypertension (PAH) probably by inhibiting endothelial
      transdifferentiation possibly via modulating Akt and Erk1/2 expressions.

PMID- 28428964
TI  - MicroRNAs-Mediated Regulation of Skeletal Muscle GLUT4 Expression and
      Translocation in Insulin Resistance.
AB  - The solute carrier family 2 facilitated glucose transporter member 4 (GLUT4)
      plays a key role in the insulin-induced glucose uptake by muscle and adipose
      tissues. In prediabetes and diabetes, GLUT4 expression/translocation has been
      detected as reduced, participating in mechanisms that impair glycemic control.
      Recently, a class of short endogenous noncoding RNAs named microRNAs (miRNAs) has
      been increasingly described as involved in the posttranscriptional epigenetic
      regulation of gene expression. The present review focuses on miRNAs potentially
      involved in the expression of GLUT4 expression, and proteins related to GLUT4 and
      translocation in skeletal muscle, seeking to correlate them with insulin
      resistance and diabetes. So far, miR-21a-5p, miR-29a-3p, miR-29c-3p, miR-93-5p,
      miR-106b-5p, miR-133a-3p, miR-133b-3p, miR-222-3p, and miR-223-3p have been
      reported to directly and/or indirectly regulate the GLUT4 expression; and their
      expression is altered under diabetes-related conditions. Besides, some miRNAs
      that have been linked to the expression of proteins involved in GLUT4
      translocation machinery in muscle could also impact glucose uptake. That makes
      these miRNAs promising targets for preventive and/or therapeutic approaches,
      which could improve glycemic control, thus deserving future new investigations.

PMID- 28428967
TI  - Keratoconus: is it a Non-inflammatory Disease?

PMID- 28428965
TI  - Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases.
AB  - Inflammation, altered immune cell phenotype, and functions are key features
      shared by diverse chronic diseases, including cardiovascular, neurodegenerative
      diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are
      innate lymphoid cells primarily involved in the immune system response to non
      self-components but their plasticity is largely influenced by the pathological
      microenvironment. Altered NK phenotype and function have been reported in several
      pathological conditions, basically related to impaired or enhanced toxicity. Here
      we reviewed and discussed the role of NKs in selected, different, and "distant"
      chronic diseases, cancer, diabetes, periodontitis, and atherosclerosis, placing
      NK cells as crucial orchestrator of these pathologic conditions.

PMID- 28428966
TI  - Nutrition and metabolism in burn patients.
AB  - Severe burn causes significant metabolic derangements that make nutritional
      support uniquely important and challenging for burned patients. Burn injury
      causes a persistent and prolonged hypermetabolic state and increased catabolism
      that results in increased muscle wasting and cachexia. Metabolic rates of burn
      patients can surpass twice normal, and failure to fulfill these energy
      requirements causes impaired wound healing, organ dysfunction, and susceptibility
      to infection. Adequate assessment and provision of nutritional needs is
      imperative to care for these patients. There is no consensus regarding the
      optimal timing, route, amount, and composition of nutritional support for burn
      patients, but most clinicians advocate for early enteral nutrition with high
      carbohydrate formulas. Nutritional support must be individualized, monitored, and
      adjusted throughout recovery. Further investigation is needed regarding optimal
      nutritional support and accurate nutritional endpoints and goals.

PMID- 28428968
TI  - Allergic Conjunctivitis in Patients with Respiratory Allergic Symptoms; a
      Retrospective Study in Greece.
AB  - Here, we report on the prevalence of allergic conjunctivitis and positive skin
      prick test (SPT) results in relation to respiratory allergic conditions among
      patients with symptoms of allergies at a respiratory outpatient clinic. A
      questionnaire survey of symptoms (i.e., asthma-like, rhinitis, and conjunctivitis
      symptoms) involving 1522 patients was carried out. The responses of 1242 patients
      indicated that they had allergic conjunctivitis, asthma, rhinitis, or a
      combination of these conditions, and 869 of these patients underwent SPTs that
      assessed responses to 40 allergens. Allergic conjunctivitis was found to be very
      common (40%, 497 out of 1242 patients) among those with symptoms of allergies.
      Conjunctivitis was slightly more common among women, while rhinitis was more
      common among men. Patients with both conjunctivitis and rhinitis were more likely
      to undergo SPTs, and they had a higher rate of positive SPTs. The coexistence of
      two or more comorbidities increased the risk of having an immunoglobulin E (IgE)
      mediated allergy (based on the SPT results) compared to having each of the
      conditions alone. In conclusion, allergic conjunctivitis can occur either alone
      or with asthma and/or rhinitis. It is not always accompanied by rhinitis, but the
      coexistence of these conditions was the strongest indicator of IgE-mediated
      allergies.

PMID- 28428970
TI  - Changes in Anterior Segment Parameters Following Pars Plana Vitrectomy Measured
      by Ultrasound Biomicroscopy (UBM).
AB  - Despite being a posterior segment ocular surgery, pars plana vitrectomy (PPV) may
      also affect anterior segment parameters. We aimed to investigate anterior segment
      alterations following PPV using ultrasound biomicroscopy (UBM) to visualize the
      structural anatomy of the eye. In this study, we enrolled phakic patients
      undergoing PPV (as the sole procedure). The anterior chamber depth, crystalline
      lens anterior-posterior (AP) diameter, anterior chamber angle, ciliary body
      dimensions, and integrity of the ciliary zonules and posterior capsule were
      assessed using UBM before and at least 3 months after PPV. Seven eyes from seven
      patients were included in the study. The indications for PPV were rhegmatogenous
      retinal detachment (57%), epiretinal membrane (29%), and macular hole (14%). The
      mean age of the patients was 57.86 +/- 6.56 years, and they were followed up for
      a mean of 131.57 +/- 29.99 days. The crystalline lens AP diameter was the only
      parameter that changed significantly following PPV (p = 0.042). Thus, increases
      in the crystalline lens AP diameter, without significant changes in the anterior
      chamber depth, can be expected after PPV due to the development of nuclear
      sclerotic cataracts.

PMID- 28428969
TI  - Targeted Lung Cancer Treatments and Eye Metastasis.
AB  - Lung cancer remains the leading cause of death due to cancer. We do not have
      effective tools for the early detection of lung cancer, so patients are usually
      diagnosed at an advanced stage. However, novel therapies based on molecular
      pathways (such as those involving the epidermal growth factor receptor,
      anaplastic lymphoma kinase, serine/threonine-protein kinase B-Raf, proto-oncogene
      tyrosine-protein kinase ROS, c-Met proto-oncogene protein, and RET proto-oncogene
      protein) are now commonly used in the treatment of lung cancer. In particular,
      these therapies are considered as first-line treatments for non-small-cell lung
      cancer. This manuscript outlines previous research on these targeted treatments,
      focusing on whether they are effective against eye metastasis.

PMID- 28428971
TI  - Retinal Research in Latin America: How Did We Get Here?
AB  - Among the numerous contributions by the Pan-American Association of Ophthalmology
      (PAAO) to the improvement of ophthalmology in Latin America, it has played an
      invaluable role in the development of the retina and vitreous subspecialty in the
      region. The quality of the research published in Latin America demonstrates the
      development of the retina subspecialty at this region and also the worldwide
      collaboration pioneered by PAAO and the Pan-American Collaborative Retina Study
      Group (PACORES). We would suggest further academic relationship at the regional
      as well as international levels as well as funding research institutes to assist
      retinal researchers in the region since it is generally thought that there is
      frequently a lack of government funding at all levels, from patient education to
      support for health teams to tertiary health care centers.

PMID- 28428972
TI  - Goldmann Applanation Tonometry: Using a Red-Free Filter for Mass Screening.

PMID- 28428973
TI  - Compression of high-density 0.16 pC electron bunches through high field gradients
      for ultrafast single shot electron diffraction: The Compact RF Gun.
AB  - We present an RF gun design for single shot ultrafast electron diffraction
      experiments that can produce sub-100 fs high-charge electron bunches in the 130
      keV energy range. Our simulations show that our proposed half-cell RF cavity is
      capable of producing 137 keV, 27 fs rms (60 fs FWHM), 106 electron bunches with
      an rms spot size of 276 MUm and a transverse coherence length of 2.0 nm. The
      required operation power is 9.2 kW, significantly lower than conventional rf
      cavity designs and a key design feature. This electron source further relies on
      high electric field gradients at the cathode to simultaneously accelerate and
      compress the electron bunch to open up new space-time resolution domains for
      atomically resolved dynamics.

PMID- 28428974
TI  - Perspective: A toolbox for protein structure determination in physiological
      environment through oriented, 2D ordered, site specific immobilization.
AB  - Revealing the structure of complex biological macromolecules, such as proteins,
      is an essential step for understanding the chemical mechanisms that determine the
      diversity of their functions. Synchrotron based X-ray crystallography and cryo
      electron microscopy have made major contributions in determining thousands of
      protein structures even from micro-sized crystals. They suffer from some
      limitations that have not been overcome, such as radiation damage, the natural
      inability to crystallize a number of proteins, and experimental conditions for
      structure determination that are incompatible with the physiological environment.
      Today, the ultra-short and ultra-bright pulses of X-ray free-electron lasers have
      made attainable the dream to determine protein structures before radiation damage
      starts to destroy the samples. However, the signal-to-noise ratio remains a great
      challenge to obtain usable diffraction patterns from a single protein molecule.
      With the perspective to overcome these challenges, we describe here a new
      methodology that has the potential to overcome the signal-to-noise-ratio and
      protein crystallization limits. Using a multidisciplinary approach, we propose to
      create ordered, two dimensional protein arrays with defined orientation attached
      on a self-assembled-monolayer. We develop a literature-based flexible toolbox
      capable of assembling different kinds of proteins on a functionalized surface and
      consider using a graphene cover layer that will allow performing experiments with
      proteins in physiological conditions.

PMID- 28428975
TI  - Parenting in Animals.
AB  - The study of parenting in animals has allowed us to come to a better
      understanding of the neural and physiological mechanisms that underlie mammalian
      parental behavior. The long-term effects of parenting (and parental abuse or
      neglect) on offspring, and the neurobiological changes that underlie those
      changes, have also been best studied in animal models. Our greater experimental
      control and ability to directly manipulate neural and hormonal systems, as well
      as the environment of the subjects, will ensure that animal models remain
      important in the study of parenting; while in the future, the great variety of
      parental caregiving systems displayed by animals should be more thoroughly
      explored. Most importantly, cross-talk between animal and human subjects research
      should be promoted.

PMID- 28428976
TI  - SEM and AFM Studies of Two-Phase Magnetic Alkali Borosilicate Glasses.
AB  - The morphology and composition of four types of two-phase alkali borosilicate
      glasses with magnetic atoms prepared by inductive melting have been studied. The
      results of scanning electron microscopy point to uniform distribution of Na, Si,
      and O atoms in these samples while magnetic iron atoms form ball-shaped
      agglomerates. The magnetic properties of these agglomerates have been confirmed
      by magnetic force microscopy. Atomic force microscopy had shown that in these
      samples two different morphological structures, drop-like and dendrite net, are
      formed. The formation of dendrite-like structure is a necessary condition for
      production of porous magnetic glasses. The obtained results allow us to optimize
      the melting and heat treatment processes leading to production of porous alkali
      borosilicate glasses with magnetic properties. The first results for
      nanocomposite materials on the basis of magnetic glasses containing the embedded
      ferroelectrics KH2PO4 demonstrate the effect of applied magnetic field on the
      ferroelectric phase transition.

PMID- 28428977
TI  - 19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016,
      Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The
      CHARGE consortium.

PMID- 28428978
TI  - 20th Workshop of the International Stroke Genetics Consortium, November 3-4,
      2016, Milan, Italy: 2016.036 ISGC research priorities.
AB  - OBJECTIVE: To develop a research priority list for the International Stroke
      Genetics Consortium (ISGC). BACKGROUND: Previously, stroke progress review groups
      and other activities provided an opportunity for members within the field to
      develop priorities for research. These filtered into larger categories which then
      published the top research priorities of their given field. However, these review
      groups are no longer forming and thus there has been no clear direction on what
      the research priorities and needs for stroke genetics research. DESIGN/METHODS:
      We polled members of the stroke genetics community from around the world
      including collaborations of the major stroke genetics research efforts currently
      under way asking each respondent to provide their top 3 research priorities. Each
      priority was then sorted by the authors into major categories based upon the type
      of suggestion made. The results were presented for commentary and feedback during
      the presentation. RESULTS: Deeper Phenotyping related topics were presented in
      84% of respondent top research priorities. These included topics related to
      ethnic/racial variation, third world countries, deeper evaluation of subtypes of
      stroke. Translational science related topics were present in 40% of respondent
      top research priorities and consisted of translating our current findings into a
      greater understanding of their relationship to stroke and clinical
      pathophysiology. Pooling of our resources through data banking and sample banking
      was a topic in 36% of respondents. Recovery/outcome related topics were suggested
      in 32% of respondents and utilizing novel techniques such as epigenetics, whole
      genome sequencing, proteomics and metabolomics were present in 28% of
      respondents. Other topics were not present in more than 25% of the responses for
      top research priorities. CONCLUSIONS: To summarize, greater sample size and
      research within subtypes and endophenotypes of stroke was the top research
      priority of the ISGC. In addition, translating our existing findings, pooling our
      resources, recovery/outcomes research and utilization of novel techniques were
      among the top research priorities of the ISGC. A working group will be assembled
      to draft the ISGC Research Priorities paper.

PMID- 28428979
TI  - Use of Consumer Wearable Devices to Promote Physical Activity: A Review of Health
      Intervention Studies.
AB  - BACKGROUND: Although many wearable devices for monitoring and tracking physical
      activity are available to consumers, relatively few research studies have been
      conducted to determine their efficacy in promoting health. METHODS: In this
      article, data on the use of consumer wearable devices in promoting healthy
      behaviors are summarized based upon bibliographic searches in PubMed and
      Psychology and Behavioral Sciences Collection with relevant search terms through
      September 2016. RESULTS: A total of 274 articles were identified in the
      bibliographic searches. By screening abstracts or full-text articles, six
      pre/post test trials and seven randomized controlled trials were identified. In
      initial trials, consumer wearable devices have been shown to increase physical
      activity and help users lose weight. However, the number of studies completed to
      date is small and limited by small sample sizes, short study durations, and
      uncertain generalizability of the findings. CONCLUSIONS: Future studies should
      utilize randomized controlled trial research designs, larger sample sizes, and
      longer study periods to better establish the efficacy of wearable devices in
      promoting physical activity. Additional research is needed to determine the
      feasibility and effectiveness of wearable devices in promoting physical activity
      and weight loss in community settings including communities affected by health
      disparities. Studies focusing on children and adolescents are also needed.

PMID- 28428980
TI  - Gram Years: A Method to Standardize and Quantify Lifetime Cannabis Consumption.

PMID- 28428981
TI  - Correction for Gonzalez et al., "Migraines Are Correlated with Higher Levels of
      Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut
      Project Cohort".
AB  - [This corrects the article DOI: 10.1128/mSystems.00105-16.].

PMID- 28428982
TI  - Biomechanical effect of pedicle screw distribution in AIS instrumentation using a
      segmental translation technique: computer modeling and simulation.
AB  - BACKGROUND: Efforts to select the appropriate number of implants in adolescent
      idiopathic scoliosis (AIS) instrumentation are hampered by a lack of
      biomechanical studies. The objective was to biomechanically evaluate screw
      density at different regions in the curve for AIS correction to test the
      hypothesis that alternative screw patterns do not compromise anticipated
      correction in AIS when using a segmental translation technique. METHODS:
      Instrumentation simulations were computationally performed for 10 AIS cases. We
      simulated simultaneous concave and convex segmental translation for a reference
      screw pattern (bilateral polyaxial pedicle screws with dorsal height
      adjustability at every level fused) and four alternative patterns; screws were
      dropped respectively on convex or concave side at alternate levels or at the
      periapical levels (21 to 25% fewer screws). Predicted deformity correction and
      screw forces were compared. RESULTS: Final simulated Cobb angle differences with
      the alternative screw patterns varied between 1 degrees  to 5 degrees  (39
      simulations) and 8 degrees  (1 simulation) compared to the reference maximal
      density screw pattern. Thoracic kyphosis and apical vertebral rotation were
      within 2 degrees  of the reference screw pattern. Screw forces were 76 +/- 43 N,
      96 +/- 58 N, 90 +/- 54 N, 82 +/- 33 N, and 79 +/- 42 N, respectively, for the
      reference screw pattern and screw dropouts at convex alternate levels, concave
      alternate levels, convex periapical levels, and concave periapical levels. Bone
      screw forces for the alternative patterns were higher than the reference pattern
      (p < 0.0003). There was no statistical bone-screw force difference between convex
      and concave alternate dropouts and between convex and concave periapical dropouts
      (p > 0.28). Alternate dropout screw forces were higher than periapical dropouts
      (p < 0.05). CONCLUSIONS: Using a simultaneous segmental translation technique,
      deformity correction can be achieved with 23% fewer screws than maximal density
      screw pattern, but resulted in 25% higher bone-screw forces. Screw dropouts could
      be either on the convex side or on the concave side at alternate levels or at
      periapical levels. Periapical screw dropouts may more likely result in lower bone
      screw force increase than alternate level screw dropouts.

PMID- 28428983
TI  - Rapid inducible protein displacement in Plasmodiumin vivo and in vitro using
      knocksideways technology.
AB  - A deeper understanding of the biology of the Plasmodium parasite is essential in
      order to identify targets for interventions, with the ultimate aim of eliminating
      malaria. Determining the function(s) of essential proteins in Plasmodium has,
      until recently, been hampered by the lack of efficient conditional systems to
      abrogate proteins. We report the adaptation of a conditional technology,
      knocksideways (KS), for use in Plasmodium berghei, which can potentially rapidly
      inactivate proteins of interest through relocalisation. The system is induced
      using rapamycin, which allows for KS both in vitro and in vivo and is effective
      more rapidly than any other reported system. KS utilises pairs of fluorescent
      tags that facilitate live imaging and allows for rapid confirmation of efficient
      protein redistribution on live parasites, allowing for streamlined workflows. We
      demonstrate the characteristics of the system using transgenically expressed
      cytoplasmic GFP and provide proof of principle by inducibly redistributing a
      number of proteins with different native, subcellular locations.  We also
      demonstrate that KS can be applied to both mammalian and insect stages of
      Plasmodium. KS expands the range of (conditional) technologies for genetic
      manipulation of malaria parasites and offers the potential to be further
      developed for medium throughput phenotype screens.

PMID- 28428985
TI  - Strain-capacitance relationship in polymer actuators based on single-walled
      carbon nanotubes and ionic liquid gels.
AB  - We investigate the electromechanical properties of bucky-gel electrochemical
      actuators incorporating various amounts of single-walled carbon nanotubes and an
      ionic liquid electrolyte, 1-butyl-3-methylimidazolium tetrafluoroborate, that are
      able to convert electrochemical energy into mechanical energy. The interplay
      between mechanical and electrochemical effects is studied. The electromechanical
      responses are investigated by means of electrochemical impedance spectroscopy and
      bending displacement measurements. We develop a theoretical model that allows us
      to rationalize the electromechanical properties of the bucky-gel actuators. This
      model takes into account electrochemical stress due to the intercalation (de
      intercalation) process, which generates the strain and bending of the actuators.
      We then analyze the relationship between the strain and the real part of the
      complex capacitance by introducing a strain-capacitance coefficient. This
      coefficient is related to the electrochemical stress and the amount of the ionic
      adsorption (desorption) at the double-layer. From a practical point of view, the
      determination of the strain-capacitance coefficient is helpful for characterizing
      and optimizing the performance of electrochemical actuators.

PMID- 28428984
TI  - A Comparison of Molecular Typing Methods Applied to Enterobacter cloacae complex:
      hsp60 Sequencing, Rep-PCR, and MLST.
AB  - Molecular typing using repetitive sequenced-based PCR (rep-PCR) and hsp60
      sequencing were applied to a collection of diverse Enterobacter cloacae complex
      isolates. To determine the most practical method for reference laboratories, we
      analyzed 71 E. cloacae complex isolates from sporadic and outbreak occurrences
      originating from 4 geographic areas. While rep-PCR was more discriminating, hsp60
      sequencing provided a broader and a more objective geographical tracking method
      similar to multilocus sequence typing (MLST). In addition, we suggest that MLST
      may have higher discriminative power compared to hsp60 sequencing, although rep
      PCR remains the most discriminative method for local outbreak investigations. In
      addition, rep-PCR can be an effective and inexpensive method for local outbreak
      investigation.

PMID- 28428986
TI  - Ruthenium-cobalt dinuclear complexes as photocatalysts for CO2 reduction.
AB  - A series of Ru-Co dinuclear complexes have been synthesized and assayed as
      photocatalysts for the reduction of CO2 to CO in organic solvents. The Ru-Co
      complexes, with tris-diimine coordination at the Co ion, are the best
      supramolecular photocatalysts for CO2 reduction with a non-noble metal catalytic
      center reported so far.

PMID- 28428987
TI  - Microarray profiling and co-expression network analysis of the lncRNAs and mRNAs
      associated with acute leukemia in adults.
AB  - Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common
      types of acute leukemia in adults and cause low survival rate and poor outcome
      after 5 years despite high rates of complete remission (CR) with modern
      chemotherapeutic regimens. To understand the distinct mechanisms in
      leukemogenesis for ALL and AML and to identify markers for diagnosis and
      treatment, lncRNA and mRNA expression profiles of AML and ALL patients and
      healthy controls were generated using microarray analysis. For comparison, the
      differentially expressed mRNA functions were annotated using gene ontology (GO)
      and pathway analysis. The microarray revealed that 1011 lncRNAs and 2656 mRNAs
      differed in AML patients and 6069 lncRNAs and 5338 mRNAs differed in ALL patients
      from those in healthy controls. The GO terms and KEGG pathway annotation data
      revealed that the olfactory receptor activity, G-protein coupled receptor
      activity and olfactory transduction-related genes were significantly associated
      with AML and ALL. Co-expression network analysis indicated that 108 lncRNAs and
      85 mRNAs were included in the co-expression network. This study is the first to
      explore genome-wide lncRNA expression and co-expression with mRNA patterns in AML
      and ALL using microarray technology and could provide basic information for new
      biomarkers or treatment targets to alleviate AML and ALL.

PMID- 28428988
TI  - Polydatin attenuates potassium oxonate-induced hyperuricemia and kidney
      inflammation by inhibiting NF-kappaB/NLRP3 inflammasome activation via the
      AMPK/SIRT1 pathway.
AB  - This study was designed to investigate the effects of polydatin (PLD) on
      potassium oxonate-induced hyperuricemic rats. Hyperuricemic rats were treated
      with potassium oxonate (250 mg kg-1) intragastrically for 7 days, and polydatin
      (25, 50 mg kg-1) or allopurinol (5 mg kg-1) was administered to the rats 1 h
      after the potassium oxonate exposure. Polydatin administration decreased the
      levels of uric acid and creatinine in serum and urine, leading to inhibition of
      pro-inflammatory cytokine production in serum and kidney. Western blot analyses
      illustrated that polydatin down-regulated the translocation of NF-kappaB p65, the
      degradation of IkappaBalpha, and the protein levels of inflammasome components
      (NLRP3, ASC, and caspase-1), which led to reduced IL-1beta secretion. Notably,
      polydatin treatment activated AMP kinase (AMPK) protein and increased SIRT1
      expression. Taken together, polydatin might be a promising agent for gouty
      treatment to inhibit renal NF-kappaB/NLRP3 inflammasome activation via the
      AMPK/SIRT1 pathway.

PMID- 28428989
TI  - Generation and characterization of the blood transcriptome of Macaca thibetana
      and comparative analysis with M. mulatta.
AB  - Transcriptome profiles provide a large transcript sequence data set for genomic
      study, particularly in organisms that have no accurate genome data published. The
      Tibetan macaque (Macaca thibetana) is commonly considered to be an endemic
      species to China and an important animal in biomedical research in the present
      day. In the present study, we report the de novo assembly and characterization of
      the blood transcriptome of the Tibetan macaque from three individuals, and we
      also sequenced the blood transcriptome of the rhesus macaque (Macaca mulatta) for
      comparison. Using RNA-seq technology, 138 million sequencing reads of the M.
      thibetana transcriptome were generated. The assembly included 327 871 transcripts
      with an N50 of 1571 bp. According to the sequence similarity search, 80 317
      (24.5%) transcripts were annotated in the nr protein database. All transcripts
      from M. thibetana and M. mulatta were functionally classified and compared using
      GO and KEGG analyses. The two transcriptomes were different in the GO term of
      nutrient reservoir activity, and in the KEGG subcategories of signaling molecules
      and interaction, infectious diseases, cell growth and death, and immune system.
      The transcriptomes in this study would provide a valuable resource for future
      functional and comparative genomic studies, and even for biological studies of
      this non-human primate.

PMID- 28428990
TI  - Nanoscale adhesion and sliding on biased semiconductors.
AB  - We present experimental and theoretical results on controlling nanoscale sliding
      friction and adhesion by electric fields on model contacts realized by bringing a
      conductive atomic force microscope tip into contact with the surface of a silicon
      oxide/silicon wafer. We find that applying a bias voltage on silicon (or on the
      conductive tip) enables a noticeable control of the sliding forces. Two
      electrostatic interactions are identified as being relevant for the friction
      variation as a function of applied voltage. The first is a short-range
      electrostatic interaction between opposite charges localized at oxide
      silicon/silicon and tip/silicon-oxide interfaces. This attractive interaction
      results from the high capacity of the oxide-semiconductor interface to change its
      charge density in response to a bias voltage. Various regimes of charging
      resulting from silicon electronic bands' alignment and deformation are evidenced.
      We mainly focused here on the strong charge accumulation and inversion domains.
      The second longer-range electrostatic interaction is between the voltage-induced
      bulk and surface charges of both tip and sample. This interaction decreases very
      slowly with the distance between tip and silicon surface, i.e. oxide thickness,
      and can be attractive or repulsive depending on voltage polarity. Our results
      demonstrate the possibility of controlling nanoscale friction/adhesion in
      nanoscale contacts involving semiconductors. These results are relevant for the
      operation of nanoscale devices or for on-surface nanomanipulation of metallic
      nanoparticles. We model the experimental results by adding an electrostatic
      energy contribution to the tip-surface binding energy, which translates into an
      increase or decrease of the normal force and ultimately of the sliding friction.

PMID- 28428991
TI  - A room-temperature phosphorescent polymer film containing a molecular web based
      on one-dimensional chiral stacking of a simple luminophore.
AB  - We propose a new approach for a totally organic, room-temperature phosphorescent
      system with a lifetime on the order of milliseconds, which is achieved by
      promotion of the one-dimensional chiral stacking of a simple, small fluorophore
      in a solution state. The versatility of this system is highlighted by its good
      applicability to the fabrication of a phosphorescent polymer film. This paper
      demonstrates the first example of a room-temperature phosphorescent polymer film
      prepared with our methodology.

PMID- 28428992
TI  - Dynamic shear force microscopy of confined liquids at a gold electrode.
AB  - The confinement of liquids in nanometer-scale gaps can lead to changes in their
      viscous shear properties. For liquids of polar molecules, the charge state of the
      confining surfaces has a significant influence on the structure in the confined
      liquid. Here we report on the implementation of dynamic shear force microscopy in
      an electrochemical cell. Lateral oscillations of the tip of an atomic force
      microscope were magnetically activated at a frequency of about 50 kHz. The
      damping of the lateral tip oscillation was recorded as a function of the tip
      sample distance and of the electrode potential at the surface of a Au(100) single
      crystal electrode. The influence of surface charges on the shear response of the
      nano-confined liquids was demonstrated for the ionic liquid [EMIM][NTf2] and for
      aqueous Na2SO4 solution.

PMID- 28428993
TI  - From nano to microcrystals: effects of different synthetic pathways on the defect
      architecture in heavily Gd-doped ceria.
AB  - The evolution of the defect structure and microstructure of heavily Gd-doped
      ceria (Ce1-MUREMUO2-y, 0.313 <= MU <= 0.438) for different synthetic pathways is
      investigated here to explore the way defects interact with each other in a
      composition range known to effectively hamper the application of the material as
      an electrolyte. Synchrotron radiation powder diffraction is exploited by
      combining conventional Rietveld analysis with the Pair Distribution Function to
      get a multiscale picture of defect structures, and it is combined with Raman
      spectroscopy to assess local scale interactions. Samples were prepared via both
      the sol-gel route and coprecipitation of oxalates by sintering the powders at
      different temperatures to obtain samples with different defect distributions and
      crystallite sizes, investigated using electron microscopy and Whole Powder
      Pattern Modelling from diffraction data. As a general scheme, increasing the
      doping amount transforms the fluorite structure of ceria into C-type Gd2O3. For
      samples annealed at and above 900  degrees C, containing crystals at least ~100
      nm in size, this transformation occurs through a mechanism involving first the
      formation of distorted Gd-rich droplets on the local scale, then the growth of
      extended C-type nanodomains. Nanoparticles, resulting from thermal treatments at
      lower temperature, are less distorted on the local scale and transform abruptly
      upon doping, without forming larger dopant-rich aggregations, from fluorite to
      the C-type. The annealing temperature not only acts on the sintering of the
      crystallites, it is also found to promote a radical change in the microstructure
      as a consequence of the preferential aggregation of oxygen vacancies.

PMID- 28428994
TI  - A facile self-templating synthesis of carbon frameworks with tailored
      hierarchical porosity for enhanced energy storage performance.
AB  - Herein, we present a facile synthesis of hierarchical carbon frameworks with
      microporous skeletons and interconnected meso/macropores by employing
      poly(vinylidene chloride-co-methyl acrylate)-b-polystyrene copolymers as
      precursors. The obtained porosity can be tuned over a broad range via well
      selected block proportions of the precursor, enabling its advantageous
      applications in target-oriented energy storage systems.

PMID- 28428995
TI  - Fluorogen-free aggregation induced NIR emission from gold nanoparticles.
AB  - Controlled diluted aqua regia addition leads to NIR (near infrared) luminescence
      from aggregated gold nanoparticles at 916 nm. This turn-on luminescence has been
      observed for gold nanoparticles, regardless of reductants used in their
      preparation. These aggregated nanoparticles are nontoxic and have been used for
      bioimaging in human liver carcinoma cells.

PMID- 28428996
TI  - Development of emissive aminopentaazaphenalene derivatives employing a design
      strategy for obtaining luminescent conjugated molecules by modulating the
      symmetry of molecular orbitals with substituent effects.
AB  - This communication describes the transformation of a non-emissive heterocycle
      into a luminophore via modulation of molecular orbitals by employing a
      dialkylamine-substituted pentaazaphenalene (A5AP) skeleton. It was presumed that
      the introduction of the amine group changed the symmetry-forbidden HOMO-LUMO (H
      L) transition to an allowed one. According to optical measurements and
      theoretical calculations, the H-L transition was turned into the symmetry-allowed
      one because of the lone pair on the nitrogen atom in the dialkylamine
      substituent. Finally, the A5AP derivatives presented significant emission from
      the H-L transition.

PMID- 28428997
TI  - Identification of Annexin A2 as a target protein for plant alkaloid matrine.
AB  - Matrine is a plant alkaloid and a major active component in the Chinese medical
      herb Sophora flavescens. Matrine has shown potent anti-cancer activities but its
      molecular target(s) and mechanism are still unknown. Using the photo-affinity
      labeling approach, for the first time, Annexin A2 was identified as a direct
      binding target of matrine in cancer cells.

PMID- 28428998
TI  - PbI2 heterogeneous-cap-induced crystallization for an efficient CH3NH3PbI3 layer
      in perovskite solar cells.
AB  - PbI2 heterogeneous-cap-induced crystallization with a face-to-face configuration
      is proposed to obtain efficient CH3NH3PbI3 perovskite films during thermal
      annealing. The films with large-size and dominative (110)-oriented grains can
      effectively boost the photovoltaic performance of the perovskite solar cells.

PMID- 28428999
TI  - Shear-induced reversibility of 2D colloidal suspensions in the presence of
      minimal thermal noise.
AB  - The effects of minimal thermal noise on particle rearrangements in cyclically
      sheared colloidal suspensions are experimentally investigated using particle
      tracking methods. Our experimental model system consists of polystyrene
      microspheres adsorbed at an oil-water interface, in which the particles exhibit
      small but non-negligible Brownian motion. Experiments are performed on bidisperse
      (1.0 and 1.2 MUm in diameter) systems, which form area fractions of 0.20 and 0.32
      at the interface. We first characterize the thermal (Brownian) noise using
      particle diffusivities at quiescent states, and show that under our experimental
      flow conditions both systems (0.20 and 0.32 area fraction) behave as athermal, in
      the sense that the particle diffusion time scale is larger than the flow time
      scale. We then characterize particle rearrangements as a function of strain
      amplitude, and show that small but finite levels of thermal noise affect the
      reversibility dynamics, even in effectively athermal systems. Our data indicate
      that as thermal noise is slightly increased in a cyclically sheared athermal
      system, the fraction of reversible rearrangements is reduced, the reversible
      cycles become unstable, and the rearrangement hysteresis is significantly
      hindered.

PMID- 28429000
TI  - Copper-catalyzed asymmetric alkynylation of cyclic N-sulfonyl ketimines.
AB  - A Cu-catalyzed asymmetric alkynylation of cyclic N-sulfonyl ketimines was
      developed, providing the corresponding chiral alpha-tertiary amines with up to
      98% ee. The method tolerates some variations in cyclic N-sulfonyl ketimine and
      alkyne scope. These products could be used in several transformations, in
      particular, the products of 6-membered cyclic N-sulfonyl ketimines could be
      easily converted to linear chiral alpha-tertiary amines. This asymmetric
      alkynylation provides an efficient, gram-scale, low-cost transition-metal
      catalyzed synthesis of chiral alpha-tetrasubstituted propargylamines.

PMID- 28429001
TI  - Structure-property relationships of cell clusters in biotissues: 2D analysis.
AB  - Gaining insight into the relationships between the self-organized cell structures
      and the properties of biotissues is helpful for revealing the function of
      biomaterials and its designing principle. However, the traditionally used random
      foam model neglects several important details of the frameworks of cell clusters
      resulting in incomplete conclusions. Herein, we use a more complete model, the
      cell adhesion model, to investigate the mechanical and morphological properties
      of the two-dimensional (2D) dry cell foams. Since these 2D structures are formed
      by cell adhesion, the system can reach equilibrium through minimizing free
      energy. Under the equilibrium conditions without volume constraint, shape
      equations for highly symmetrical structures are derived, and the analytical
      results of the corresponding mechanical parameters, such as the Young's modulus,
      bulk modulus and failure strength, are obtained. Moreover, with volume
      constraint, numerical simulation method is applied to study the complex shapes
      and obtain several stable multicellular structures. Symmetry breaking caused by
      the volume change is also observed. Moreover, typical periodic shapes and the
      corresponding phase transformations are also explored. Our study provides a new
      potential method to bridge the microstructure and macro-mechanical parameters of
      biotissues. The results are also useful for understanding the formation mechanism
      of biotissue structures.

PMID- 28429002
TI  - Assembling metallic 1T-MoS2 nanosheets with inorganic-ligand stabilized quantum
      dots for exceptional solar hydrogen evolution.
AB  - Due to their enhanced light harvesting, favored interfacial charge transfer and
      excellent proton reduction activity, hybrid photocatalysts of metallic 1T-MoS2
      nanosheets and inorganic-ligand stabilized CdSe/ZnS QDs obtained via a self
      assembly approach can produce H2 gas with a rate of ~155 +/- 3.5 MUmol h-1 mg-1
      under visible-light irradiation (lambda = 410 nm), the most exceptional
      performance of solar H2 evolution using MoS2 as a cocatalyst known to date.

PMID- 28429003
TI  - Electrochemical plasmonic metamaterials: towards fast electro-tuneable reflecting
      nanoshutters.
AB  - Self-assembling arrays of metallic nanoparticles at liquid|liquid or liquid|solid
      interfaces could deliver new platforms for tuneable optical systems. Such systems
      can switch between very-high and very-low reflectance states upon assembly and
      disassembly of nanoparticles at the interface, respectively. This encourages
      creation of electro-variably reversible mirror/window nanoplasmonic devices.
      However, the response time of these systems is usually limited by the rate-of
      diffusion of the nanoparticles in the liquid, towards the interface and back. A
      large time-constant implies slow switching of the system, challenging the
      practical viability of such a system. Here we introduce a smart alternative to
      overcome this issue. We propose obtaining fast switching via electrically-induced
      rotation of a two-dimensional array of metal nanocuboids tethered to an ITO
      substrate. By applying potential to the ITO electrode the orientation of
      nanocuboids can be altered, which results in conversion of a highly-reflective
      nanoparticle layer into a transparent layer (or vice versa) within sub-second
      timescales. A theoretical method is developed based on the quasi-static effective
      medium approach to analyse the optical response of such arrays, which is verified
      against full-wave simulations. Further theoretical analysis and estimates based
      on the potential energy of the nanoparticles in the two orientations corroborate
      the idea that voltage-controlled switching between the two states of a
      nanoparticle assembly is a viable option.

PMID- 28429004
TI  - Binding site opening by loop C shift and chloride ion-pore interaction in the
      GABAA receptor model.
AB  - GABAA receptors (GABAARs) are crucial in mediating inhibition in the adult
      mammalian brain. Although the kinetics of this receptor has been extensively
      studied, the molecular picture of interactions occurring at various channel
      conformations remains elusive. While electrophysiology combined with mutagenesis
      sheds light on the role of specific residues, ultrastructural studies reveal
      static structures which, in the case of GABAARs, are limited to the beta3
      homomer. To take advantage of the newest crystal structures of cys-loop
      receptors, a homology model of alpha1beta2gamma2 GABAAR in the unbound closed
      state was built using a template of the homomeric glycine receptor in the closed
      state. The template model contained strychnine molecules at the binding sites
      which were removed and molecular dynamics was used to study the system
      relaxation. The modeled GABAAR preserved the closed conformation. Two interfaces
      forming orthosteric binding sites (beta2/alpha1) exhibited opening due to the
      outward shift of loop C. Similar movement, although less pronounced, was observed
      at the alpha1/gamma2 (modulatory) interface. In contrast, interfaces alpha1/beta2
      and gamma2/beta2 remained closed. The former one, due to interactions mediated
      mainly by loops C and F, affected the neighboring beta2/alpha1 interface leading
      to asymmetry between the orthosteric binding sites. Such interactions were not
      observed at the beta2/alpha1 interface preceded by a gamma2 subunit. As expected,
      in the channel pore, the conserved leucine gate and selectivity filter were
      present. However, an additional constriction was found at the top of the pore
      which differed from a typical hydrophobic channel gate as it consisted of charged
      residues. Interestingly, this site showed a capacity to trap chloride ions and to
      undergo conformation transition-like expansion, suggesting an impact on pore
      properties. In conclusion, our homology model faithfully reproduced major
      features of heteromeric GABAARs offering insight into the underlying mechanisms
      of stabilizing the shut conformation and chloride ion interaction with the
      channel pore.

PMID- 28429005
TI  - Carborane-based polymers: a novel class of semiconductors with tunable
      properties.
AB  - Semiconducting boron carbides based on cross-linked carborane (B10C2H12)
      icosahedra, developed several decades ago, are of significant interest in a
      variety of emerging areas, including photocatalysis, spintronics, and especially
      neutron detection. These materials, however, display generally poor charge
      carrier mobility, high defect levels and other properties that pose significant
      drawbacks. A class of nanocomposite carborane-based materials has recently been
      developed, that addresses many of these issues. The films consist of polymerized
      mixtures of carboranes and aromatic species, including benzene, 1,4
      diaminobenzene, pyridine or aniline. In these materials, electronic states
      corresponding to the aromatic moiety appearing near the top of the valence band,
      and states associated with the carborane moiety occupy the bottom of the
      conduction band. Band gap energies are substantially reduced relative to films
      without aromatic content. Transport measurements also indicate that charge
      scattering lifetimes are substantially enhanced in aromatic/carborane films
      compared to corresponding films without aromatic content. This combination of
      superior electron-hole separation, narrower band gaps, and superior charge
      scattering lifetimes, yields markedly enhanced charge collection in neutron
      voltaics studies compared to conventional carborane-derived boron carbides. The
      implications of these enhanced properties for neutron detection and other
      applications are discussed.

PMID- 28429006
TI  - Correction: Ag+-induced photoluminescence enhancement in lanthanide post
      functionalized MOFs and Ag+ sensing.
AB  - Correction for 'Ag+-induced photoluminescence enhancement in lanthanide post
      functionalized MOFs and Ag+ sensing' by Nana Sun et al., Phys. Chem. Chem. Phys.,
      2017, 19, 9174-9180.

PMID- 28429007
TI  - Tuning the electrical conductivity of exfoliated graphite nanosheets nanofluids
      by surface functionalization.
AB  - The electrical conductivity of exfoliated graphite in water nanofluids has been
      experimentally determined, and compared with the same property when the dispersed
      nanosheets have been oxidized. The effect of oxidation on this property is
      different if compared with the case of sintered dry nanosheets. In any case, for
      the sintered raw material the conduction behaves as expected in a metal, while
      for the nanofluid it shows values and trends typical of a weak electrolyte
      solution. The effect of oxidation on the electrical conductivity of exfoliated
      graphite can be explained as being caused by the dissociation in the fluid phase
      of the moieties resulting from the chemical functionalization process. This opens
      the possibility of designing a functionalization process to tune the nanofluid
      electrical conductivity.

PMID- 28429008
TI  - Anticancer effects of novel resveratrol analogues on human ovarian cancer cells.
AB  - Resveratrol, a naturally occurring phytoalexin, has long been known to play an
      important regulatory role in key functions in cell physiology. This
      multifunctional role of resveratrol is explained by its ability to interact with
      several targets of various cell pathways. In the recent past, synthetic chemical
      modifications have been made in an attempt to enhance the biological effects of
      resveratrol, including its anti-cancer properties. In this study, we investigated
      the molecular mechanisms of action of novel trans-restricted analogues of
      resveratrol in which the C-C double bond of the natural derivative has been
      replaced by diaryl-substituted imidazole analogues. In ovarian cancer models, the
      results of in vitro screening revealed that the resveratrol analogues exhibited
      enhanced anti-proliferative properties compared with resveratrol. We found that
      the resveratrol analogues also significantly inhibited Akt and MAPK signalling
      and reduced the migration of IL-6 and EGF-treated cells. Finally, in ascite
      derived cancer cells, we demonstrated that the resveratrol analogues reduced the
      expression of epithelial mesenchymal transition (EMT) markers. Collectively,
      these findings indicate the enhanced anti-cancer properties of the resveratrol
      analogues.

PMID- 28429009
TI  - Aggregation of cyclic polypeptoids bearing zwitterionic end-groups with
      attractive dipole-dipole and solvophobic interactions: a study by small-angle
      neutron scattering and molecular dynamics simulation.
AB  - Aggregation behavior of cyclic polypeptoids bearing zwitterionic end-groups in
      methanol has been studied using a combination of experimental and simulation
      techniques. The data from SANS and cryo-TEM indicate that the solution contains
      small clusters of these cyclic polypeptoids, ranging from a single polypeptoid
      chain to small oligomers, while the linear counterpart shows no cluster
      formation. Atomistic molecular dynamics simulations reveal that the driving force
      for this clustering behavior is due to the interplay between the effective
      repulsion due to the solvation of the dipoles formed by the charged end-groups in
      each polypeptoid chain and the attractive forces due to dipole-dipole
      interactions and the solvophobic effect.

PMID- 28429010
TI  - Going beyond the three-state ensemble model: the electronic chemical potential
      and Fukui function for the general case.
AB  - Making use of the grand canonical ensemble the derivation of the analytical
      equations for the chemical potential and the Fukui function in the general case
      of any number of ground and excited states is presented. The expressions thus
      obtained allow one to establish that the ensemble of three consecutive ground
      states that has been usually used to analyze the effects of temperature in these
      quantities provides a satisfactory description for them at temperatures of
      chemical interest. Nevertheless, some situations must be considered cautiously,
      as for example, when the N + k and N + k + 1 (N is the electron number) ground
      states are (nearly) quasidegenerate or when the first excited state of both the
      anion and the cation (with respect to the reference state) is very low in energy.
      Results for the copper atom (with the ground state of Cu+ as the reference
      state), using some selected ensemble models constituted by several ground and
      excited states, are presented to show that the very low-lying excited states of
      some of the copper species are able to contribute to chemical reactivity at
      relatively low temperatures (~2000 K). A relevant aspect is that due to its
      generality, the present approach provides a new way to study the reactivity of
      the chemical species under extreme conditions.

PMID- 28429011
TI  - Drop transport and positioning on lubricant-impregnated surfaces.
AB  - We demonstrate the transport and positioning of water droplets on macro-patterned
      lubricant-impregnated surfaces. The macro-patterning produces menisci features in
      the impregnating liquid layer which interact with a droplet via a capillary
      mechanism similar to the Cheerios effect. These interactions control the droplet
      motion and positioning on an otherwise completely slippery surface. We present
      experimental results using a V-shape channel geometry as a model system. The
      interaction between deformations on the lubricant layer induced by the droplet
      and the underlying V-shape geometry leads to both local and global equilibrium
      positions for the droplet within the channel. We present a mathematical model to
      quantify the transition from local equilibrium states to the global equilibrium
      state and show that the latter can be described on the basis of a force balance
      along the apparent contact line of the droplet. We highlight possible
      applications where lubricated macro-patterned surfaces can be used to control the
      motion and localisation of droplets.

PMID- 28429012
TI  - Correction: Identifying the optimal anticancer targets from the landscape of a
      cancer-immunity interaction network.
AB  - Correction for 'Identifying the optimal anticancer targets from the landscape of
      a cancer-immunity interaction network' by Chunhe Li et al., Phys. Chem. Chem.
      Phys., 2017, 19, 7642-7651.

PMID- 28429013
TI  - A stochastic model for directional changes of swimming bacteria.
AB  - In this work we introduce a stochastic model to describe directional changes in
      the movement of swimming bacteria. We use the probability density function (PDF)
      of turn angles, measured on tumbling wild-type E. coli, to build a Langevin
      equation for the deflection of the bacterial body swimming in isotropic media. We
      have solved this equation analytically by means of the Green function method and
      shown that three parameters are sufficient to describe the movement: the
      characteristic time, the steady-state solution and the control parameter. We
      conclude that the tumble motion, which is manifested as abrupt turns, is
      primarily caused by the rotational boost generated by the flagellar motor and
      complementarily by the rotational diffusion introduced by noise. We show that in
      the tumble motion the deflection is a non-stationary stochastic process during
      times at which the tumbling occurs. By tuning the control parameter our model is
      able to explain small turns of the bacteria around their centres of mass along
      the run. We show that the deflection during the run is an Ornstein-Uhlenbeck
      process, which for typical run times is stationary. We conclude that, along the
      run, the rotational boosts do not exist and that only the rotational diffusion
      remains. Thus we have a single model to explain the turns of the bacterium during
      the run or tumble movements, through a control parameter that can be tuned
      through a critical value that can explain the transition between the two turn
      behaviours. This model is also able to explain in a very satisfactory way all
      available statistical experimental data, such as PDFs and average values of
      turning angles times, of both run and tumble motions.

PMID- 28429014
TI  - Formation of mono- and binuclear neodymium(iii)-gluconate complexes in aqueous
      solutions in the pH range of 2-8.
AB  - The complex formation between Nd(iii) and d-gluconate (Gluc-) is of relevance in
      modelling the chemical equilibria of radioactive waste repositories. In the
      present work, the formation of NdpGlucqH-r complexes at 25  degrees C and pH = 2
      8 was studied via spectrophotometry, potentiometry, freezing point depression,
      conductometry and NMR spectroscopy. In addition to the four mononuclear complexes
      (pq-r = 110, 120, 130 and 11-2), the formation of two binuclear, so far unknown
      complexes (pq-r = 23-2 and 24-2) was revealed. Between pH = 5.5 and 7, with the
      increasing metal ion and ligand concentrations, the Nd2Gluc3H-2+ species becomes
      progressively predominant. Under the conditions characteristic of waste
      repositories, however, the formation of these complexes can be neglected.
      Regarding the binding sites of Gluc-, C2-OH and C3-OH groups, in addition to the
      carboxylate ion, were identified from 1H and 13C spectroscopic measurements.
      Above pH = 6, the metal-ligand interactions became stronger implying the
      formation of deprotonated complexes involving the C2-OH group, while the
      displacement of the second proton at the C3-OH is also possible. The metal ion
      induced deprotonation of the ligand was confirmed by DFT calculations.

PMID- 28429015
TI  - Asymmetric electroosmotic pumping across porous media sandwiched with perforated
      ion-exchange membranes.
AB  - To have non-zero net flow in AC electroosmotic pumps, the electroosmosis (EO) has
      to be non-linear and asymmetric. This can be achieved due to ionic concentration
      polarization. This is known to occur close to micro-/nano-interfaces provided
      that the sizes of the nanopores are not too large compared to the Debye screening
      length. However, operation of the corresponding EO pumps can be quite sensitive
      to the solution concentration and, thus, unstable in practical applications.
      Concentration polarization of ion-exchange membranes is much more robust.
      However, the hydraulic permeability of the membrane is very low, which makes EO
      flows through them extremely small. This communication shows theoretically how
      this problem can be resolved via making scarce microscopic perforations in an ion
      exchange membrane and putting it in series with an EO-active nano-porous medium.
      The problem of coupled flow, concentration and electrostatic-potential
      distributions is solved numerically by using finite-element methods. This
      analysis reveals that even quite scarce perforations of micron-scale diameters
      are sufficient to observe practically-interesting EO flows in the system. If the
      average distance between the perforations is smaller than the thickness of the EO
      active layer, there is an effective homogenization of the electrolyte
      concentration and hydrostatic pressure in the lateral direction at some distance
      from the interface. The simulations show this distance to be somewhat lower than
      the half-distance between the perforations. On the other hand, when the surface
      fraction of perforations is sufficiently small (below a fraction of a percent)
      this "homogeneous" concentration is considerably reduced (or increased, depending
      on the current direction), which makes the EO strongly non-linear and asymmetric.
      This analysis provides initial guidance for the design of high-productivity and
      inexpensive AC electroosmotic pumps.

PMID- 28429016
TI  - Synergetic effects of K+ and Mg2+ ion intercalation on the electrochemical and
      actuation properties of the two-dimensional Ti3C2 MXene.
AB  - Two-dimensional materials, such as MXenes, are attractive candidates for energy
      storage and electrochemical actuators due to their high volume changes upon ion
      intercalation. Of special interest for boosting energy storage is the
      intercalation of multivalent ions such as Mg2+, which suffers from sluggish
      intercalation and transport kinetics due to its ion size. By combining
      traditional electrochemical characterization techniques with electrochemical
      dilatometry and contact resonance atomic force microscopy, the synergetic effects
      of the pre-intercalation of K+ ions are demonstrated to improve the charge
      storage of multivalent ions, as well as tune the mechanical and actuation
      properties of the Ti3C2 MXene. Our results have important implications for
      quantitatively understanding the charge storage processes in intercalation
      compounds and provide a new path for studying the mechanical evolution of energy
      storage materials.

PMID- 28429017
TI  - Oligonucleotide promoted peptide bond formation using a tRNA mimicking approach.
AB  - TransferRNA's role in protein translation is the prime example of an
      Informational Leaving Group (ILG). A simplified model produced oligophenylalanine
      with a modified uracil as an ILG in the presence of specific oligonucleotides.
      Our preliminary studies contribute to the importance of hybrid species in
      bridging the gap between peptides and nucleic acids.

PMID- 28429018
TI  - Force-induced elastic matrix-mediated interactions in the presence of a rigid
      wall.
AB  - We consider a soft elastic matrix that contains particulate inclusions and is
      bounded by a rigid wall, e.g., the substrate. Such a situation arises in elastic
      composite materials. They may serve as soft actuators when forces are imposed on
      or induced between the embedded particles. We investigate how the presence of the
      rigid wall affects the interactions between the inclusions. First, for no-slip
      boundary conditions, we transfer Blake's derivation of a corresponding Green's
      function from low-Reynolds-number hydrodynamics to the linearly elastic case.
      Then, we list the general expressions to describe the situation for point-like
      particles in the presence of no-slip and free-slip surface conditions. To compare
      the effect of the different surface conditions to each other and to the bulk
      behavior, we address the example situation of pairwise interactions between two
      embedded particles. The axis through both particle centers is either aligned
      parallel or perpendicular to the surface. Our results suggest that walls with
      free-slip surface conditions are preferred when they serve as substrates for soft
      actuators made from elastic composite materials. As we further demonstrate, the
      presence of a rigid wall can qualitatively change the interactions between the
      inclusions. In effect, it can switch attractive interactions into repulsive ones
      (and vice versa). It should be straightforward to observe the effects in future
      experiments and to combine our results, e.g., with the modeling of biological
      cells and tissue on rigid surfaces.

PMID- 28429019
TI  - Facile syntheses of pure uranium halides: UCl4, UBr4 and UI4.
AB  - Herein we describe convenient lab scale syntheses of several uranium(iv) halides
      of high purity by reaction of AlX3 (X = Cl, Br and I) with UO2, which is readily
      available by reduction of uranyl salts like UO2(NO3)2.6H2O. UCl4, UBr4, and UI4
      are obtained in the form of aggregates of large single crystals. Their identities
      and purity were checked by powder X-ray diffraction, IR spectroscopy and
      elemental analysis. The syntheses introduced here avoid the need for pure
      metallic uranium and are based on more readily available starting materials, UO2,
      which does not even have to be pure, and the respective aluminium halide.
      Chemical vapor transport (CVT) is applied in situ for purification of the
      products.

PMID- 28429020
TI  - Catalysis for Fuels: general discussion.

PMID- 28429021
TI  - Preparation and characterization of metastable trigonal layered MSb2O6 phases (M
      = Co, Ni, Cu, Zn, and Mg) and considerations on FeSb2O6.
AB  - MSb2O6 compounds (M = Mg, Co, Ni, Cu, Zn) are known in the tetragonal trirutile
      forms, slightly distorted monoclinically with M = Cu due to the Jahn-Teller
      effect. In this study, using a low-temperature exchange reaction between ilmenite
      type NaSbO3 and molten MSO4-KCl (or MgCl2-KCl) mixtures, these five compositions
      were prepared for the first time as trigonal layered rosiaite (PbSb2O6)-type
      phases. Upon heating, they irreversibly transform to the known phases via
      amorphous intermediates, in contrast to previously studied isostructural MnSb2O6,
      where the stable phase is structurally related to the metastable phase. The same
      method was found to be applicable for preparing stable rosiaite-type CdSb2O6. The
      formula volumes of the new phases show an excellent correlation with the ionic
      radii (except for M = Cu, for which a Jahn-Teller distortion is suspected) and
      are 2-3% larger than those for the known forms although all coordination numbers
      are the same. The crystal structure of CoSb2O6 was refined via the Rietveld
      method: P3[combining macron]1m, a = 5.1318(3) A, and c = 4.5520(3) A. Compounds
      with M = Co and Ni antiferromagnetically order at 11 and 15 K, respectively,
      whereas the copper compound does not show long-range magnetic order down to 1.5
      K. A comparison between the magnetic behavior of the metastable and stable
      polymorphs was carried out. FeSb2O6 could not be prepared because of the 2Fe2+ +
      Sb5+ = 2Fe3+ + Sb3+ redox reaction. This electron transfer produces an additional
      5s2 shell for Sb and results in a volume increase. A comparison of the formula
      volume for the stable mixture FeSbO4 + 0.5Sb2O4 with that extrapolated for
      FeSb2O6 predicted that the trirutile-type FeSb2O6 can be stabilized at high
      pressures.

PMID- 28429022
TI  - Dependence of gold nanoparticle radiosensitization on cell geometry.
AB  - The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated
      both in vitro and in vivo in radiation therapy. The purpose of this study was to
      systematically assess the biological effectiveness of GNPs distributed in the
      extracellular media for realistic cell geometries. TOPAS-nBio simulations were
      used to determine the nanometre-scale radial dose distributions around the GNPs,
      which were subsequently used to predict the radiation dose response of cells
      surrounded by GNPs. MDA-MB-231 human breast cancer cells and F-98 rat glioma
      cells were used as models to assess different cell geometries by changing (1) the
      cell shape, (2) the nucleus location within the cell, (3) the size of GNPs, and
      (4) the photon energy. The results show that the sensitivity enhancement ratio
      (SER) was increased up to a factor of 1.2 when the location of the nucleus is
      close to the cell membrane for elliptical-shaped cells. Heat-maps of damage
      likelihoods show that most of the lethal events occur in the regions of the
      nuclei closest to the membrane, potentially causing highly clustered damage
      patterns. The effect of the GNP size on radiosensitization was limited when the
      GNPs were located outside the cell. The improved modelling of the cell geometry
      was shown to be crucial because the dose enhancement caused by GNPs falls off
      rapidly with distance from the GNPs. We conclude that radiosensitization can be
      achieved for kV photons even without cellular uptake of GNPs when the nucleus is
      shifted towards the cell membrane. Furthermore, damage was found to concentrate
      in a small region of the nucleus in close proximity to the extracellular, GNP
      laden region.

PMID- 28429023
TI  - Probing the role of excited states in ionization of acetylene.
AB  - Ionization of acetylene by linearly-polarized, vacuum ultraviolet (VUV) laser
      pulses is modelled using time-dependent density functional theory. Several laser
      wavelengths are considered including one that produces direct ionization to the
      first excited cationic state while another excites the molecules to a Rydberg
      series incorporating an autoionizing state. We show that for the wavelengths and
      intensities considered, ionization is greatest whenever the molecule is aligned
      along the laser polarization direction. By considering high harmonic generation
      we show that populating excited states can lead to a large enhancement in the
      harmonic yield. Lastly, angularly-resolved photoelectron spectra are calculated
      which show how the energy profile of the emitted electrons significantly changes
      in the presence of these excited states.

PMID- 28429024
TI  - A highly efficient Cu catalyst system for the radical reactions of alpha
      bromocarbonyls.
AB  - In this communication, we established highly efficient Cu-catalyzed ARGET-ATRS
      (atom-transfer radical substitution) of alpha-bromocarbonyls with styrenes to
      produce tert-alkylated styrenes. The maximum TON was up to 12 000. Hunig's base
      was very important to regenerate active CuI. Moreover, a Cu-catalyzed C-C
      cleavage reaction via SH2' and intermolecular C-H cyclization of alpha-bromoimide
      was found.

PMID- 28429025
TI  - Nanoscale controlled Li-insertion reaction induced by scanning electron-beam
      irradiation in a Li4Ti5O12 electrode material for lithium-ion batteries.
AB  - The development of a nanoscale battery reaction in an electrode material
      associated with in situ microscopic observation is significant to an
      understanding of the solid-state mechanism of a battery reaction. With a
      Li4Ti5O12 (LTO) crystal as the negative electrode of a Li-ion battery (LIB), we
      show that a nanoscale-controlled Li-insertion reaction can be produced by
      electron beam irradiation with scanning transmission electron microscopy (STEM).
      A selected area in a Li2O-coated thin LTO crystal was irradiated by the electron
      probe of STEM with a high beam intensity of 2.5 * 107 (electrons per nm2).
      Electron energy-loss spectroscopy (EELS) revealed that significant changes in the
      chemical feature occurred only in the high-dose irradiation area in the LTO
      specimen. The features of Li-K, Ti-L and O-K spectra in that area were completely
      equal to those of a Li7Ti5O12 (Li-LTO) phase, as an electrochemically Li-inserted
      LTO phase, in contrast to usual LTO-like spectra in the region surrounding the
      specimen. For a pristine LTO specimen without Li2O coating, no Li-insertion
      reaction was observed under the same irradiation conditions. The high-dose
      electron beam seems to induce the dissociation of Li2O, providing Li ions and
      electrons, and the rapid and directional growth of a Li-LTO phase along the
      electron beam in the LTO specimen, forming a nanoscale steep interface with the
      surrounding LTO phase. The present phenomenon is a new type of electron beam
      assisted chemical reaction in a solid state, and could have a large impact on the
      science and technology of battery materials.

PMID- 28429026
TI  - N-Difluoromethyl-triazole as a constrained scaffold in peptidomimetics.
AB  - The N-difluoromethyl triazolo-beta-aza-epsilon-amino acid present in the core of
      peptides led to constrained conformations due to CH-F and NH-F interactions.
      Pseudotetrapeptides were obtained in excellent yields directly by click chemistry
      between azidodifluoroacetamides and alkynes, both linked to an amino acid. This
      work demonstrates that the N-difluoromethyltriazole scaffold can induce extended
      structures to beta-strand mimics.

PMID- 28429027
TI  - A metabolomic study on high-risk stroke patients determines low levels of serum
      lysine metabolites: a retrospective cohort study.
AB  - Identifying changes in serum metabolites during cerebral ischemia is an important
      approach for early diagnosis of thrombotic stroke. Herein, we highlight novel
      biomarkers for early diagnosis of patients at high risk of thrombotic stroke
      using high resolution metabolomics (HRM). In this retrospective cohort study,
      serum samples obtained from patients at risk of thrombotic stroke (n  =  62) and
      non-risk individuals (n  =  348) were tested using HRM, coupled with LC-MS/MS, to
      discriminate between metabolic profiles of control and stroke risk patients.
      Multivariate analysis and orthogonal partial least square-discriminant analysis
      (OPLS-DA) were performed to determine the top 5% metabolites within 95% group
      identities, followed by filtering with p-value <0.05 and annotating significant
      metabolites using a Metlin database. Mapping identified features from Kyoto
      Encyclopedia of Genes and Genomes (KEGG) and Mummichog resulted in 341
      significant features based on OPLS-DA with p-value <0.05. Among these 341
      features, nine discriminated the thrombotic stroke risk group from the control
      group: low levels of N6-acetyl-l-lysine, 5-aminopentanoate, cadaverine, 2
      oxoglutarate, nicotinamide, l-valine, S-(2-methylpropionyl)-dihydrolipoamide-E
      and ubiquinone, and elevated levels of homocysteine sulfinic acid. Further
      analysis showed that these metabolite biomarkers are specifically related to
      stroke occurrence, and unrelated to other factors such as diabetes or smoking.
      Lower levels of lysine catabolites in thrombotic stroke risk patients, as
      compared to the control, supports targeting these compounds as novel biomarkers
      for early and non-invasive detection of a thrombotic stroke.

PMID- 28429028
TI  - Experimental separation steps influence the protein content of corona around
      mesoporous silica nanoparticles.
AB  - In order to direct nanocarriers to their targets efficiently, we have to
      understand the interactions occurring at the nano-bio interface between
      nanocarriers and human proteins, which forms the layer called the corona.
      However, experiments aiming to identify and quantify the proteins in the corona,
      especially critical steps in the separation of nanoparticles from biological
      media may affect the corona composition. Here, we used nano-LC MS/MS to compare
      the protein corona contents obtained after using two different separation
      methods. We showed that applying centrifugation versus magnetization to isolate
      nanoparticles surrounded by a corona resulted in protein loss and a reshuffling
      of their respective abundances.

PMID- 28429029
TI  - Derivatization and interlaminar debonding of graphite-iron nanoparticle hybrid
      interfaces using Fenton chemistry.
AB  - The interfacial debonding of graphite lattices using iron (Fe) nanoparticles and
      Fenton's reagent is reported, towards the scalable production of few-layer
      graphene flakes. Acoustic cavitation via a sonochemical route was adapted to
      produce iron and iron oxide nanoparticles in the graphite matrix. The oxygenated
      species were introduced into the graphite lattice using a physical method, and
      then Fenton chemistry was utilized to generate localized hydroxyl radicals at the
      Fe nanoparticle-graphite interfaces for zipping and self-exfoliation of the
      defected graphite lattices. The functional groups were found to have been
      introduced predominately at the periphery of the flake, confirming that the
      lateral dimension of graphene had not been affected, and at the same time, good
      dispersion in organic solvents had been achieved. Defect engineering could be
      modulated at the organic-inorganic hybrid interfaces, in order to control the
      zipping rate and regulate the degree of functionalization and the lateral
      dimensions of the graphene sheet.

PMID- 28429030
TI  - Comment on: Glioblastoma multiforme outcomes of 107 patients treated in two local
      institutions.

PMID- 28429031
TI  - Infectious diseases in Singapore and Asia: persistent challenges in a new era.

PMID- 28429032
TI  - Obstructive sleep apnoea and Type 2 diabetes mellitus: are they connected?
AB  - Obstructive sleep apnoea (OSA), a sleep-related breathing condition, is diagnosed
      based on a patient's apnoea-hypopnea index from a sleep study, and the presence
      or absence of symptoms. Diabetes mellitus (DM) and OSA share a significant common
      risk factor, obesity, with all three conditions contributing to the risk of
      developing cardiovascular diseases. The pathophysiological links between OSA and
      DM are still unclear, but intermittent hypoxia may be an important mechanism.
      More awareness of the possible link between OSA and DM is needed, given their
      increasing prevalence locally and worldwide. Continuous positive airway pressure
      is the standard treatment for OSA, while weight loss through dietary and
      lifestyle modifications is important to holistically manage patients with either
      condition. There is currently insufficient evidence to support the benefits of
      screening every diabetic patient for OSA. However, diabetic patients with
      symptoms suggestive of OSA should be referred to a sleep specialist for further
      evaluation.

PMID- 28429034
TI  - Authors' reply.

PMID- 28429033
TI  - Clinics in diagnostic imaging (176). Acute embolic occlusion of the coeliac
      artery.
AB  - A 52-year-old man, who had a background of chronic heart disease and atrial
      fibrillation, as well as non-compliance with warfarin therapy, presented with a
      two-week history of worsening upper abdominal pain. Computed tomography
      mesenteric angiography showed complete embolic occlusion of the coeliac artery
      with resultant segmental splenic infarction, and thrombus within the left
      ventricle. A decision was made to proceed with catheter-directed thrombolysis.
      Subsequent follow-up angiogram at 12 hours showed successful treatment with
      complete dissolution of the coeliac embolus. The patient's symptoms resolved
      during his hospitalisation and he was subsequently discharged well on long-term
      oral anticoagulation therapy. Isolated acute embolic occlusion of the coeliac
      axis is a rare occurrence that may result in end-organ infarction. Treatment
      options include systemic anti-coagulation, mechanical thrombectomy, catheter
      thrombolysis or open surgery. Catheter-directed thrombolysis therapy is a
      feasible and effective option for treating acute thromboembolic occlusion of the
      coeliac artery.

PMID- 28429035
TI  - Max Theiler (1899-1972): Creator of the yellow fever vaccine.

PMID- 28429037
TI  - Double jeopardy in acute ST-segment elevation myocardial infarction.

PMID- 28429036
TI  - A review of Zika virus infections in pregnancy and implications for antenatal
      care in Singapore.
AB  - Given the consensus that there is a causal relationship between Zika virus (ZIKV)
      infection in pregnancy and congenital Zika syndrome (CZS), clinicians must be
      prepared to manage affected patients despite the numerous gaps in current
      knowledge. The clinical course in pregnancy appears similar to that in non
      pregnant women, although viraemia may be prolonged. ZIKV infection can be
      diagnosed by serum and urine reverse transcription-polymerase chain reaction, but
      commercially available serological tests are currently unreliable in dengue
      endemic regions. Although vertical transmission can occur at any time during
      gestation, first- and second-trimester infections have the highest risk of
      developing central nervous system anomalies. Aberrant fetal growth and pregnancy
      loss may also occur. Serial ultrasonography should be conducted for infected
      cases. Without a vaccine, pregnant women should be advised to minimise mosquito
      bites and reduce sexual transmission risk. Overall, the absolute risk of CZS
      arising amid a ZIKV outbreak appears relatively low.

PMID- 28429038
TI  - [Phosphodiesterase 4 inhibition for treatment of endothelial barrier and
      microcirculation disorders in sepsis].
AB  - Sepsis is commonly associated with loss of microvascular endothelial barrier
      function (capillary leak) and dysfunctional microcirculation, which both promote
      organ failure. The development of a distinct therapy of impaired endothelial
      barrier function and disturbed microcirculation is highly relevant because both
      of these phenomena constitute crucial processes which critically influence the
      prognosis of patients. Numerous in vivo and in vitro trials over the past years
      have fostered a better understanding of the pathophysiology of capillary leak.
      Furthermore, promising data in animal models show that therapeutic modulation of
      endothelial barrier function and microcirculation can be achieved by stabilizing
      endothelial cAMP (cyclic adenosine monophosphate) levels followed by activation
      of Rho-GTPase Rac1, e. g. by phosphodiesterase 4 inhibitors. This review
      summarizes and discusses recent findings of cellular mechanisms and in vivo
      trials.

PMID- 28429039
TI  - [True thymic hyperplasia : Differential diagnosis of thymic mass lesions in
      neonates and children].
AB  - Reactive and neoplastic thymic pathologies are the main considerations in the
      case of masses in the anterior and middle part of the mediastinum, while
      neurogenic tumors are predominant in the posterior mediastinum (which are not
      dealt with here). In neonates and infants, the commonest pathologies in the
      anterior mediastinum comprise germ cell tumors (mainly teratomas), congenital
      thymic cysts and true thymic hyperplasia (TTH). In toddlers, teratomas, yolk sac
      tumors and cysts predominate. In children over 5 years of age, lymphomas are the
      commonest mass lesions whereas thymomas and thymic carcinomas are rare. In
      addition, inflammation-linked hyperplasia in myasthenia gravis and rebound thymic
      hyperplasia after chemotherapy must be considered. Although rare at all ages,
      sarcomas must be considered in the differential diagnosis from birth onwards and
      throughout adolescence. Based on the report of a rare case of recurrent TTH, the
      differential diagnosis of this benign but potentially life-threatening condition
      is discussed.

PMID- 28429040
TI  - Retraction force necessary to expose the mandibular neck in Risdon and high
      cervical anteroparotid transmasseteric approaches: an anatomic comparative study.
AB  - PURPOSE: The purpose of this anatomic study was to compare the retraction force
      necessary to expose the mandibular neck in the Risdon and the high cervical
      anteroparotid transmasseteric (HAT) approaches. METHODS: An anatomic study was
      performed on 18 formalin-embalmed cadavers. We performed a Risdon approach on the
      left side, and an HAT approach on the right side in all the cases. The subjects
      were placed in a normative frame and the force necessary to maintain a
      satisfactory exposure of the condyle was measured with a system of cables,
      pulleys, and mechanical dynamometer. The statistical comparison between the two
      sides was carried out using the Wilcoxon signed-rank test for paired series.
      RESULTS: In all the cases, the region of interest was exposed as in the operating
      room. In the Risdon approach, the mean force was 32 Newtons (4-47). In the HAT
      approach, the mean force was 19 Newtons (4-33). The difference was statistically
      significant (p < 0.001). The age, gender, and duration of conservation had no
      influence on the retraction force. CONCLUSION: In the HAT approach, the
      retraction of the soft tissues was significantly lower than in the Risdon
      approach. This study gave an additional explanation to the remarkable safety of
      the HAT approach. Our results were in favor of the generalization of this
      technique.

PMID- 28429041
TI  - [The benefits of drainage after deep rectal anastomosis].

PMID- 28429042
TI  - [Julius Springer Prize for Surgery 2017 awarded].

PMID- 28429043
TI  - Transsplenic endovascular recanalization and stenting of a completely occluded
      portal vein with jejunal variceal embolization in a pediatric liver transplant
      recipient.
AB  - Portal vein thrombosis occurs in 1.4% of pediatric liver transplant candidates
      and 3.7% of liver transplant recipients. While portal vein recanalization without
      and with portal vein stenting has been described in adult transplant candidates
      and recipients, it has never been described in the pediatric transplant
      population. This report presents a pediatric liver transplant recipient with
      portal hypertension secondary to portal vein thrombosis successfully managed with
      transsplenic access and subsequent portal vein recanalization and stenting.

PMID- 28429044
TI  - 68Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma: a lesion-by-lesion
      comparison with 111In-octreotide SPECT/CT and conventional imaging.
AB  - PURPOSE: The aim of this study was to prospectively compare the detection rate of
      68Ga-DOTATATE PET-CT with 111In-octreotide SPECT-CT and conventional imaging (CI)
      in medullary thyroid carcinoma (MTC) patients with increased calcitonin (Ctn)
      levels but negative CI after thyroidectomy. METHODS: Fifteen patients with raised
      Ctn levels and/or CI evidence of recurrence underwent 68Ga-DOTATATE PET-CT, 111In
      octreotide SPECT-CT and CI. Histopathology, CI and biochemical/clinical/imaging
      follow-up were used as the reference standard. PET/CT, SPECT/CT and CI were
      compared in a lesion-based and organ-based analysis. RESULTS: PET/CT evidenced
      recurrence in 14 of 15 patients. There were 13 true positive (TP), 1 true
      negative (TN), 1 false positive (FP) and no false negative (FN) cases, resulting
      in a sensitivity and accuracy of 100% and 93%. SPECT/CT was positive in 6 of 15
      cases. There were 6 TP, 2 TN, 7 FN and no FP cases, resulting in a sensitivity of
      46% and accuracy of 53%. CI procedures detected tumor lesions in 14 of 15
      patients. There were 13 TP, 1TN, 1 FP and no FN cases with a sensitivity of 100%
      and accuracy of 93%. A significantly higher number of lesions was detected by
      PET/CT (112 lesions, p = 0.005) and CI (109 lesions, p = 0.005) in comparison to
      SPECT/CT (16 lesions). There was no significant difference between PET/CT and CI
      for the total number of detected lesions (p = 0.734). PET/CT detected more
      lesions than SPECT/CT regardless of the organ. PET/CT detected more bone lesions
      but missed some neck nodal metastases evidenced by CI. The number of lesions per
      region demonstrated by PET/CT and CI were similar in the other sites. CONCLUSION:
      68Ga-DOTATATE PET/CT is superior to 111In-octreotide SPECT/CT for the detection
      of recurrent MTC demonstrating a significantly higher number of lesions. 68Ga
      DOTATATE PET/CT showed a superior detection rate compared to CI in demonstrating
      bone metastases.

PMID- 28429045
TI  - Assessment of the alpha angle and mobility of the hip in patients with noncontact
      anterior cruciate ligament injury.
AB  - PURPOSE: To evaluate the alpha angle of the hip in patients with noncontact
      anterior cruciate ligament (ACL) injury and compare it with patients without
      injury. In addition, external and internal rotation of the hip was assessed and
      correlated with the alpha angle. METHODS: The alpha angle of the ipsilateral hip
      was assessed in 41 subjects with non-contact ACL tear and compared with 39
      subjects with no tear. The external and internal rotation of the ipsilateral hip
      was also evaluated. RESULTS: The alpha angle was larger in subjects with
      noncontact ACL injury. The mean was 70.31 degrees  (+/-13.92 degrees ) compared
      with 58.55 degrees  (+/-13.95 degrees ) in the control group (p < 0.001). The
      groups were similar when considering the external, internal, and sum of rotation
      of the ipsilateral hip. There was no correlation between the alpha angle and
      decreased rotational range of motion of the hip in either group (p > 0.05).
      CONCLUSION: Patients with noncontact ACL injury presented a greater alpha angle
      when compared with the group without tear. There was no difference in the
      rotational mobility of the hip between groups, nor was there a correlation
      between the increase in the alpha angle and the decrease in the rotational
      mobility of the hip.

PMID- 28429046
TI  - Western Ontario Shoulder Instability Index: cross-cultural adaptation and
      validation of the Turkish version.
AB  - One way to measure the effectiveness of a specific treatment is to utilize
      measurements designed specifically for the disorder. Western Ontario Shoulder
      Instability Index (WOSI) is a subjective self-report scale indicating the latest
      condition of the patients with shoulder instability. The objective is to study
      the cultural adaptation, validity, and reliability of WOSI in Turkish population
      with shoulder disability. First, WOSI was translated and culturally adapted from
      English into Turkish. Afterward, in order to determine the level of reliability,
      internal consistency and test-retest analyses were conducted. Reliability (test
      retest) analyses were conducted by means of retest 72 h later with a sub-group of
      30 patients. Construct validity of the WOSI was checked through convergent
      validity with Disabilities of Arm, Shoulder and Hand Scale, Rowe Score
      Questionnaire, Oxford Shoulder Instability Questionnaire, and Western Ontario
      Rotator Cuff Index by 60 patients with shoulder instability. The Turkish version
      of the questionnaire displayed high internal consistency (0.77-0.91) with a
      Cronbach's Alpha value of 0.91. As for the test-retest reliability, the ICC value
      was found to be high (95% CI 0.97). Floor and ceiling effects (15%) were observed
      neither in sub-parameters (0-4.9%) nor in total score (0%). WOSI total score was
      found to have a negative good correlation with the Rowe Score (r = -0.57) and a
      very good-excellent correlation with other questionnaires (r = 0.67-0.89). The
      Turkish version of WOSI is a valid and reliable scale for use in studies to
      evaluate the final condition of the patients with shoulder disabilities.

PMID- 28429047
TI  - Therapeutic outcome of CT-guided radiofrequency ablation in patients with osteoid
      osteoma.
AB  - OBJECTIVE: To assess the long-term outcome of computed tomography-guided
      radiofrequency ablation (CT-guided RFA) in patients with suspected osteoid
      osteoma (OO). MATERIALS AND METHODS: Single-center retrospective study. Patients
      with clinical suspicion and imaging diagnosis of osteoid osteoma were treated by
      CT-guided RFA using the same device with either a 7- or 10-mm active tip
      electrode. Specific precautions were applied in case of articular or spinal OO.
      Patients were contacted by phone to evaluate the long-term outcome in terms of
      pain, ability to perform daily activities (including sports), and long-term
      complications. Success was defined as the absence of residual pain and ability to
      perform daily activities normally. RESULTS: From 2008 to 2015, 126 patients were
      treated by CT-guided RFA for OO in our institution. Mean patient age was 26.1
      years (SD = 11, range 1-53); mean delay to diagnosis was 16.9 months (SD = 15.2,
      range 1-120). Among patients who answered the follow-up call (n = 88), the
      overall success rate was 94.3%: 79/88 (89.8%) had primary success of the
      procedure, and 4/88 (4.5%) had a secondary success (repeat-RFA after pain
      recurrence). Mean follow-up time was 34.6 months (SD = 24.7, range 3-90). Few
      complications occurred: two mild reversible peripheral nerve injuries, one
      brachial plexus neuropathy, one broken electrode tip fragment, and one muscular
      hematoma. CONCLUSION: Osteoid osteoma can be effectively and safely treated by CT
      guided RFA using the presented ablation protocol. Beneficial effects of the
      treatment persist at long-term follow-up.

PMID- 28429048
TI  - Myxofibrosarcoma: First report of myxofibrosarcoma of bone arising at a bone
      infarct.
AB  - Approximately 3300 new primary bone tumors will present to American physicians
      this year. This small but important group of malignancies has become more defined
      with developments in pathologic morphology, immunohistochemistry, and molecular
      studies. As tumor types are better partitioned, their specific characteristics
      are more readily observed. In this article we present the first reported case of
      a myxofibrosarcoma of bone developing within a bone infarct. With improved
      delineation of rarer tumor types, it is expected that additional cases of
      myxofibrosarcoma of bone will be recognized, potentially arising from a bone
      infarct. By framing the context, describing the case, and sharing pertinent
      figures, we hope to facilitate this recognition.

PMID- 28429050
TI  - Assessment of Cr, Ni and Pb Pollution in Rural Agricultural Soils of Tonalite
      Trondjhemite Series in Central India.
AB  - Chromium (Cr), nickel (Ni) and lead (Pb) contamination was investigated in wheat
      cultivated rain-fed and irrigated rural agricultural soils (n = 31) of Tonalite
      Trondjhemite Series in Central India. The soil sampling was carried out by using
      stratified random sampling method. The mean concentrations of Cr, Ni and Pb were
      54.8, 38.1 and 68.9 mg/kg, respectively. The average values of enrichment factor
      (EF), geoaccumulation index (I geo ) and contamination factor (CF) followed the
      order as: Pb > Ni > Cr. Distribution patterns of soil parent material and
      weathering processes govern mineral enrichments, irrespective of rainfed or
      irrigated agricultural practices. Principal component analysis (PCA) showed
      strong loading of Cr and Ni (PC1) and Pb and clay (PC3). The strong loading on Cr
      and Ni indicates soils are originating from basic and volcanic rocks in the study
      area. The strong loading of Pb and clay indicates Pb is strongly adsorbed on clay
      minerals and Fe-oxides. The cancer risk (CR) index showed negligible carcinogenic
      risk to the residing population. However, hazard index (HI) values for children
      exceed the safe limit (HI > 1) for Cr and Pb. Spatial distribution of pollution
      load index suggest highest pollution in the northeastern part of the district.
      The study revealed that geogenically enriched soils of the area are suitable for
      agricultural activities under present conditions.

PMID- 28429049
TI  - Dysregulation of haematopoietic stem cell regulatory programs in acute myeloid
      leukaemia.
AB  - Haematopoietic stem cells (HSC) are situated at the apex of the haematopoietic
      differentiation hierarchy, ensuring the life-long supply of mature haematopoietic
      cells and forming a reservoir to replenish the haematopoietic system in case of
      emergency such as acute blood loss. To maintain a balanced production of all
      mature lineages and at the same time secure a stem cell reservoir, intricate
      regulatory programs have evolved to control multi-lineage differentiation and
      self-renewal in haematopoietic stem and progenitor cells (HSPCs). Leukaemogenic
      mutations commonly disrupt these regulatory programs causing a block in
      differentiation with simultaneous enhancement of proliferation. Here, we briefly
      summarize key aspects of HSPC regulatory programs, and then focus on their
      disruption by leukaemogenic fusion genes containing the mixed lineage leukaemia
      (MLL) gene. Using MLL as an example, we explore important questions of wider
      significance that are still under debate, including the importance of cell of
      origin, to what extent leukaemia oncogenes impose specific regulatory programs
      and the relevance of leukaemia stem cells for disease development and prognosis.
      Finally, we suggest that disruption of stem cell regulatory programs is likely to
      play an important role in many other pathologies including ageing-associated
      regenerative failure.

PMID- 28429051
TI  - Induction chemotherapy followed by concurrent chemoradiotherapy vs. concurrent
      chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a
      retrospective cohort study.
AB  - PURPOSE: To evaluate the efficacy and toxicity of induction chemotherapy followed
      by concurrent chemoradiotherapy vs. concurrent chemoradiotherapy for
      locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: We reviewed data
      of locoregionally advanced NPC patients who underwent 2 different treatment
      plans, 1 with induction chemotherapy followed by concurrent chemoradiotherapy (IC
      + CCRT) and the other with only concurrent chemoradiotherapy (CCRT). All patients
      received cisplatin 80 mg/m2 3 weeks one cycle concurrently with intensity
      modulated radiation therapy, and three IC protocols were included for the IC +
      CCRT group. RESULTS: Data of 262 patients treated from May 2011 to November 2014
      were found eligible for our study. With a median follow-up of 29.02 months, no
      significant differences were detected between the two groups on the 2-year
      overall survival or OS rates (96.63 vs. 92.86%, P = 0.169), 2-year distant
      metastasis-free survival or DMFS rates (91.57 vs. 86.90%, P = 0.246) and 3-year
      DMFS rates (90.45 vs. 82.14%, P = 0.093). However, they were statistically
      different on 2-year locoregional failure-free survival or LFFS rates (94.94 vs.
      86.90%, P = 0.020), 3-year OS rates (95.51 vs. 82.14%, P = 0.002) and 3-year LFFS
      rates (93.82 vs. 79.76%, P = 0.001). The most common severe (grade 3-4) adverse
      events we recorded were Nausea/vomiting (36.52 vs. 33.33%), leukopenia (14.04 vs.
      4.76%), thrombocytopenia (3.93 vs. 3.57%) and hepatic toxicity (3.37 vs. 2.38%).
      CONCLUSION: Compared with CCRT, the treatment plan IC + CCRT produced
      significantly encouraging outcomes in locoregionally advanced NPC patients on
      local progression-free survival and 3-year overall survival position, but might
      raise the risk of certain adverse reactions.

PMID- 28429052
TI  - The skeletal impact of the chemotherapeutic agent etoposide.
AB  - : Effects of the chemotherapeutic agent etoposide on the skeleton were determined
      in mice. Numbers of bone marrow cells were reduced and myeloid cells were
      increased. Bone volume was significantly decreased with signs of inhibition of
      bone formation. Etoposide after pre-treatment with zoledronic acid still reduced
      bone but overall bone volume was higher than with etoposide alone. INTRODUCTION:
      Chemotherapeutics target rapidly dividing tumor cells yet also impact
      hematopoietic and immune cells in an off target manner. A wide array of therapies
      have negative side effects on the skeleton rendering patients osteopenic and
      prone to fracture. This study focused on the pro-apoptotic chemotherapeutic agent
      etoposide and its short- and long-term treatment effects in the bone marrow and
      skeleton. METHODS: Six- to 16-week-old mice were treated with etoposide (20-25
      mg/kg) or vehicle control in short-term (daily for 5-9 days) or long-term
      (3*/week for 17 days or 6 weeks) regimens. Bone marrow cell populations and their
      phagocytic/efferocytic functions were analyzed by flow cytometry. Blood cell
      populations were assessed by CBC analysis. Bone volume and area compartments and
      osteoclast numbers were measured by microCT, histomorphometry, and TRAP staining.
      Biomarkers of bone formation (P1NP) and resorption (TRAcP5b) were assayed from
      serum. Gene expression in bone marrow was assessed using qPCR. RESULTS: Flow
      cytometric analysis of the bone marrow revealed short-term etoposide reduced
      overall cell numbers and B220+ cells, with increased marrow apoptotic
      (AnnexinV+PI-) cells, mesenchymal stem-like cells, and CD68+, CD45+, and CD11b+
      monocyte/myeloid cells (as a percent of the total marrow). After 6 weeks, the
      CD68+, Gr1+, CD11b+, and CD45+ cell populations were still relatively increased
      in etoposide-treated bone marrow. Skeletal phenotyping revealed etoposide
      decreased bone volume, trabecular thickness, and cortical bone volume. Gene
      expression in the marrow for the leptin receptor and CXCL12 were reduced with
      short-term etoposide, and an increased ratio of RANKL/OPG mRNA was observed. In
      whole bone, Runx2 and osteocalcin gene expressions were reduced, and in serum,
      P1NP was significantly reduced with etoposide. Treatment with the antiresorptive
      agent zoledronic acid prior to etoposide increased bone volume and improved the
      etoposide-induced decrease in skeletal parameters. CONCLUSIONS: These data
      suggest that etoposide induces apoptosis in the bone marrow and significantly
      reduces parameters of bone formation with rapid reduction in bone volume. Pre
      treatment with an antiresorptive agent results in a preservation of bone mass.
      Preventive approaches to preserving the skeleton should be considered in human
      clinical studies.

PMID- 28429053
TI  - Self-assessment of treatment compliance with antimuscarinic drugs and lower
      urinary tract condition among women with urinary incontinence.
AB  - AIM: Our aim was to determine the efficiency of the Medication Compliance Self
      Report Inventory (MASRI) in self-reporting antimuscarinic drug treatment
      compliance among women with urinary incontinence (UI). MATERIALS AND METHODS: The
      study assessed 347 women aged 18-65 (averaging 49.7) years with more than one
      urinary incontinence (UI) episode per day. Treatment compliance was tested at the
      beginning and at weeks 4, 8, and 12 using the MASRI, the Brief Medication
      Questionnaire (BMQ), and visual pill counts. The MASRI's constructive,
      concurrent, and discriminate validity was studied in comparison with an external
      standard that uses the chi-square and Spearman coefficient. Receiver operating
      characteristic (ROC) analysis was performed to identify optimum MASRI cutoffs
      that would predict noncompliance. Furthermore, the functional condition of the
      lower urinary tract was tested using voiding diaries, uroflowmetry, and
      cystometry. RESULT: The correlation between the percentage of noncompliant women
      according to the MASRI, and individuals with a belief barrier with respect to the
      BMQ screen was r = 0.81 (p <=0.05), r = 0.84 (p <=0.05), and r = 0.79 (p <=0.05).
      The correlation between the percentage of noncompliant women according to the
      MASRI and of women who missed >20% of their doses according to the Regimen Screen
      of the BMQ was r = 0.79, p <=0.05, r = 0.82, p <=0.01, r = 0.77, and p <=0.05 at
      the control points. Finally, the percentage of noncompliant patients who self
      reported correctly according to the MASRI data compared with the BMQ was 95.6%,
      95.7%, and 96.6% at the control points. CONCLUSION: The MASRI entails acceptable
      validity for accurately predicting treatment compliance with antimuscarinic drugs
      among women who have had UI for >3 months.

PMID- 28429054
TI  - Variables affecting maximum urethral closure pressure (MUCP) and abdominal leak
      point pressure (ALPP) measurements.
AB  - INTRODUCTION AND HYPOTHESIS: The relationship between pelvic floor muscles and
      measurements of urethral function is not well studied. It is not known whether
      adjusting for clinical, demographic and urodynamic parameters would improve the
      association between MUCP and ALPP. Our hypothesis was that pelvic floor muscle
      strength (PFMS) influences the relationship between MUCP and ALPP. METHODS: This
      was a retrospective study of women who underwent a complex urodynamic study with
      evaluation of MUCP and ALPP using ICD-9 codes with documentation of PFMS.
      RESULTS: Urodynamic stress incontinence was confirmed in 478 patients, of whom
      323 had MUCP recorded and 263 had both MUCP and ALPP recorded. Women with higher
      PFMS had a higher MUCP. In regression analysis ALPP at 150 mL and MUCP were
      weakly associated (coefficient 0.43, 95% CI 0.08-0.78; p = 0.02), whereas ALPP at
      capacity and MUCP were moderately associated (coefficient 0.60, 95% CI 0.25-0.95;
      p < 0.001). CONCLUSIONS: This study showed that MUCP and ALPP at 150 mL were
      weakly associated and that this improved to a moderate association for ALPP at
      capacity. MUCP increased with increasing PFMS among women with stress urinary
      incontinence and decreased with increasing age. There was no evidence that ALPP
      was associated with PFMS or age. The relationship between MUCP and ALPP was
      unchanged when accounting for covariates of PFMS (age, parity, BMI, prior
      procedure, urethral mobility, bladder capacity, stage of cystocele, or stage of
      uterine or apical prolapse).

PMID- 28429055
TI  - Diagnostic value of fourth-generation iterative reconstruction algorithm with low
      dose CT protocol in assessment of mesorectal fascia invasion in rectal cancer:
      comparison with magnetic resonance.
AB  - PURPOSE: The purpose of the article is to compare the diagnostic performance
      about radiation dose and image quality of low-dose CT with iterative
      reconstruction algorithm (iDose4) and standard-dose CT in the assessment of
      mesorectal fascia (MRF) invasion in rectal cancer patients. MATERIALS AND
      METHODS: Ninety-one patients with biopsy-proven primary rectal adenocarcinoma
      underwent CT staging: 42 underwent low-dose CT, 49 underwent standard CT
      protocol. Low-dose contrast-enhanced MDCT scans were performed on a 256 (ICT,
      Philips) scanner using 120 kV, automated mAs modulation, iDose4 iterative
      reconstruction algorithm. Standard-dose MDCT scans were performed on the same
      scanner with 120 kV, 200-300 mAs. All patients underwent a standard lower abdomen
      MR study (on 1.5T magnet), including multiplanar sequences, considered as
      reference standard. Diagnostic accuracy of MRF assessment was determined on CT
      images for both CT protocols and compared with MRI images. Dose-length product
      (DLP) and CT dose index (CTDI) calculated for both groups were compared and
      statistically analyzed. RESULTS: Low-dose protocol with iDose4 showed high
      diagnostic quality in assessment of MRF with significant reduction (23%; p =
      0.0081) of radiation dose (DLP 2453.47) compared to standard-dose examination
      (DLP 3194.32). CONCLUSIONS: Low-dose protocol combined with iDose4 reconstruction
      algorithm offers high-quality images, obtaining significant radiation dose
      reduction, useful in the evaluation of MRF involvement in rectal cancer patients.

PMID- 28429056
TI  - Prognostic significance of supradiaphragmatic lymph nodes at initial presentation
      in patients with stage III high-grade serous ovarian cancer.
AB  - PURPOSE: To identify the optimal size threshold and to assess the prognostic
      significance of supradiaphragmatic lymph nodes at initial presentation of
      patients with high-grade serous ovarian cancer (HGSC). METHODS: This IRB
      approved, HIPAA-compliant retrospective study included baseline pretreatment
      staging abdominal CTs of 88 women (mean age 62 years, SD 10.4, range 29-85) with
      FIGO stage III HGSC. Patients with stage IV disease were excluded due to worse
      prognosis and management guided by distant metastases. Two fellowship-trained
      radiologists independently reviewed abdominal CTs to record the presence of
      supradiaphragmatic nodes, abdominal lymphadenopathy, peritoneal carcinomatosis,
      and ovarian mass. Progression-free survival (PFS) and overall survival (OS) were
      recorded after median 79 months follow-up (IQR 58-115, range 13-144). The optimal
      short-axis size threshold for supradiaphragmatic lymphadenopathy was determined
      by correlating 3, 4, 5, 6, 7, and 10 mm thresholds with PFS and OS using Log-rank
      test. Prognostic significance of supradiaphragmatic lymphadenopathy was assessed
      using Cox proportional hazards models. RESULTS: There was good interobserver
      agreement for presence (kappa = 0.65, 95%CI 0.51-0.79) and size (ICC = 0.77,
      95%CI 0.66-0.86) of supradiaphragmatic nodes. 5 mm short-axis size threshold was
      associated with significantly shorter PFS (median 14 months, IQR 11-17 vs. 23
      months, IQR 12-59; p = 0.02) and OS (median 44 months, IQR 27-69 vs. 65 months,
      IQR 45-96; p = 0.03). Total 38/88 (43%) patients had supradiaphragmatic
      lymphadenopathy. On Cox proportion hazards analysis, supradiaphragmatic
      lymphadenopathy was significantly associated with shorter PFS (p = 0.02; HR 1.81,
      95%CI 1.11-2.96) and OS (p = 0.008; HR 2.11, 95%CI 1.21-3.65). CONCLUSION: In
      patients with stage III HGSC, supradiaphragmatic lymphadenopathy is associated
      with shorter PFS and OS. Further studies would help determine its implications on
      staging, decision regarding neoadjuvant therapy, and surgical technique.

PMID- 28429057
TI  - Characterisation of three fungal glucuronoyl esterases on glucuronic acid ester
      model compounds.
AB  - The glucuronoyl esterases (GEs) that have been identified so far belong to family
      15 of the carbohydrate esterases in the CAZy classification system and are
      presumed to target ester bonds between lignin alcohols and (4-O-methyl-)D
      glucuronic acid residues of xylan. Few GEs have been cloned, expressed and
      characterised to date. Characterisation has been done on a variety of synthetic
      substrates; however, the number of commercially available substrates is very
      limited. We identified novel putative GEs from a wide taxonomic range of fungi
      and expressed the enzymes originating from Acremonium alcalophilum and Wolfiporia
      cocos as well as the previously described PcGE1 from Phanerochaete chrysosporium.
      All three fungal GEs were active on the commercially available compounds benzyl
      glucuronic acid (BnGlcA), allyl glucuronic acid (allylGlcA) and to a lower degree
      on methyl glucuronic acid (MeGlcA). The enzymes showed pH stability over a wide
      pH range and tolerated 6-h incubations of up to 50  degrees C. Kinetic parameters
      were determined for BnGlcA. This study shows the suitability of the commercially
      available model compounds BnGlcA, MeGlcA and allylGlcA in GE activity screening
      and characterisation experiments. We enriched the spectrum of characterised GEs
      with two new members of a relatively young enzyme family. Due to its
      biotechnological significance, this family deserves to be more extensively
      studied. The presented enzymes are promising candidates as auxiliary enzymes to
      improve saccharification of plant biomass.

PMID- 28429058
TI  - Effects of genome duplication on phenotypes and industrial applications of
      Saccharomyces cerevisiae strains.
AB  - Polyploidy is common in Saccharomyces cerevisiae strains, but the physiological
      and phenotypic effects of ploidy changes have not been fully clarified. Here,
      isogenic diploid, triploid, and tetraploid S. cerevisiae strains were constructed
      from a haploid strain, CEN.PK2-1C. Stress tolerance and ethanol fermentation
      performance of the four euploid strains were compared. Each euploid strain had
      strengths and weaknesses in tolerance to certain stressors, and no single strain
      was tolerant of all stressors. The diploid had higher ethanol production than the
      other strains in normal fermentation medium, while the triploid strain showed the
      fastest fermentation rate in the presence of inhibitors found in lignocellulosic
      hydrolysate. Physiological determination revealed diverse physiological
      attributes, such as trehalose, ergosterol, glutathione, and anti-oxidative
      enzymes among the strains. Our analyses suggest that both ploidy parity and
      number of chromosome sets contribute to changes in physiological status. Using
      qRT-PCR, different expression patterns of genes involved in the regulation of
      cell morphology and the biosynthesis of key physiological attributes among
      strains were determined. Our data provide novel insights into the multiple
      effects of genome duplication on yeast cells and are a useful reference for
      breeding excellent strains used in specific industrial applications.

PMID- 28429059
TI  - A novel method to recover inclusion body protein from recombinant E. coli fed
      batch processes based on phage PhiX174-derived lysis protein E.
AB  - Production of recombinant proteins as inclusion bodies is an important strategy
      in the production of technical enzymes and biopharmaceutical products. So far,
      protein from inclusion bodies has been recovered from the cell factory through
      mechanical or chemical disruption methods, requiring additional cost-intensive
      unit operations. We describe a novel method that is using a bacteriophage-derived
      lysis protein to directly recover inclusion body protein from Escherichia coli
      from high cell density fermentation process: The recombinant inclusion body
      product is expressed by using a mixed feed fed-batch process which allows
      expression tuning via adjusting the specific uptake rate of the inducing
      substrate. Then, bacteriophage PhiX174-derived lysis protein E is expressed to
      induce cell lysis. Inclusion bodies in empty cell envelopes are harvested via
      centrifugation of the fermentation broth. A subsequent solubilization step
      reveals the recombinant protein. The process was investigated by analyzing the
      impact of fermentation conditions on protein E-mediated cell lysis as well as
      cell lysis kinetics. Optimal cell lysis efficiencies of 99% were obtained with
      inclusion body titers of >2.0 g/l at specific growth rates higher 0.12 h-1 and
      inducer uptake rates below 0.125 g/(g * h). Protein E-mediated cell disruption
      showed a first-order kinetics with a kinetic constant of -0.8 +/- 0.3 h-1. This
      alternative inclusion body protein isolation technique was compared to the one
      via high-pressure homogenization. SDS gel analysis showed 10% less protein
      impurities when cells had been disrupted via high-pressure homogenization, than
      when empty cell envelopes including inclusion bodies were investigated. Within
      this contribution, an innovative technology, tuning recombinant protein
      production and substituting cost-intensive mechanical cell disruption, is
      presented. We anticipate that the presented method will simplify and reduce the
      production costs of inclusion body processes to produce technical enzymes and
      biopharmaceutical products.

PMID- 28429060
TI  - Engineered jadomycin analogues with altered sugar moieties revealing JadS as a
      substrate flexible O-glycosyltransferase.
AB  - Glycosyltransferases (GTs)-mediated glycodiversification studies have drawn
      significant attention recently, with the goal of generating bioactive compounds
      with improved pharmacological properties by diversifying the appended sugars. The
      key to achieving glycodiversification is to identify natural and/or engineered
      flexible GTs capable of acting upon a broad range of substrates. Here, we report
      the use of a combinatorial biosynthetic approach to probe the substrate
      flexibility of JadS, the GT in jadomycin biosynthesis, towards different non
      native NDP-sugar substrates, enabling us to identify six jadomycin B analogues
      with different sugar moieties. Further structural engineering by precursor
      directed biosynthesis allowed us to obtain 11 new jadomycin analogues. Our
      results for the first time show that JadS is a flexible O-GT that can utilize
      both L- and D- sugars as donor substrates, and tolerate structural changes at the
      C2, C4 and C6 positions of the sugar moiety. JadS may be further exploited to
      generate novel glycosylated jadomycin molecules in future glycodiversification
      studies.

PMID- 28429061
TI  - Natural Resource Management Schemes as Entry Points for Integrated Landscape
      Approaches: Evidence from Ghana and Burkina Faso.
AB  - In recognition of the failures of sectoral approaches to overcome global
      challenges of biodiversity loss, climate change, food insecurity and poverty,
      scientific discourse on biodiversity conservation and sustainable development is
      shifting towards integrated landscape governance arrangements. Current landscape
      initiatives however very much depend on external actors and funding, raising the
      question of whether, and how, and under what conditions, locally embedded
      resource management schemes can serve as entry points for the implementation of
      integrated landscape approaches. This paper assesses the entry point potential
      for three established natural resource management schemes in West Africa that
      target landscape degradation with involvement of local communities: the Chantier
      d'Amenagement Forestier scheme encompassing forest management sites across
      Burkina Faso and the Modified Taungya System and community wildlife resource
      management initiatives in Ghana. Based on a review of the current literature, we
      analyze the extent to which design principles that define a landscape approach
      apply to these schemes. We found that the CREMA meets most of the desired
      criteria, but that its scale may be too limited to guarantee effective landscape
      governance, hence requiring upscaling. Conversely, the other two initiatives are
      strongly lacking in their design principles on fundamental components regarding
      integrated approaches, continual learning, and capacity building. Monitoring and
      evaluation bodies and participatory learning and negotiation platforms could
      enhance the schemes' alignment with integrated landscape approaches.

PMID- 28429062
TI  - Detection of freshwater cyanotoxins and measurement of masked microcystins in
      tilapia from Southeast Asian aquaculture farms.
AB  - Recently, there has been a rise in freshwater harmful algal blooms (HABs)
      globally, as well as increasing aquaculture practices. HABs can produce
      cyanotoxins, many of which are hepatotoxins. An ultra-performance liquid
      chromatography tandem mass spectrometry method was developed and validated for
      nine cyanotoxins across three classes including six microcystins, nodularin,
      cylindrospermopsin and anatoxin-a. The method was used to analyse free
      cyanotoxin(s) in muscle (n = 34), liver (n = 17) and egg (n = 9) tissue samples
      of 34 fish sourced from aquaculture farms in Southeast Asia. Conjugated
      microcystin was analysed by Lemieux oxidation to ascertain the total amount of
      microcystin present in muscle. Some tilapia accumulated free microcystin-LR in
      the muscle tissue at a mean of 15.45 MUg/kg dry weight (dw), with total
      microcystin levels detected at a mean level of 110.1 MUg/kg dw, indicating that
      the amount of conjugated or masked microcystin present in the fish muscle
      accounted for 85% of the total. Higher levels of cyanotoxin were detected in the
      livers, with approximately 60% of those tested being positive for microcystin-LR
      and microcystin-LF, along with cylindrospermopsin. Two fish from one of the
      aquaculture farms contained cylindrospermopsin in the eggs; the first time this
      has been reported. The estimated daily intake for free and total microcystins in
      fish muscle tissue was 2 and 14 times higher, respectively, than the tolerable
      daily intake value. This survey presents the requirement for further monitoring
      of cyanotoxins, including masked microcystins, in aquaculture farming in these
      regions and beyond, along with the implementation of guidelines to safeguard
      human health. Graphical abstract ?.

PMID- 28429063
TI  - Direct fluorescence anisotropy assay for cocaine using tetramethylrhodamine
      labeled aptamer.
AB  - Development of simple, sensitive, and rapid method for cocaine detection is
      important in medicine and drug abuse monitoring. Taking advantage of fluorescence
      anisotropy and aptamer, this study reports a direct fluorescence anisotropy (FA)
      assay for cocaine by employing an aptamer probe with tetramethylrhodamine (TMR)
      labeled on a specific position. The binding of cocaine and the aptamer causes a
      structure change of the TMR-labeled aptamer, leading to changes of the
      interaction between labeled TMR and adjacent G bases in aptamer sequence, so FA
      of TMR varies with increasing of cocaine. After screening different labeling
      positions of the aptamer, including thymine (T) bases and terminals of the
      aptamer, we obtained a favorable aptamer probe with TMR labeled on the 25th base
      T in the sequence, which exhibited sensitive and significant FA-decreasing
      responses upon cocaine. Under optimized assay conditions, this TMR-labeled
      aptamer allowed for direct FA detection of cocaine as low as 5 MUM. The maximum
      FA change reached about 0.086. This FA method also enabled the detection of
      cocaine spiked in diluted serum and urine samples, showing potential for
      applications. Graphical Abstract The binding of cocaine to the TMR-labeled
      aptamer causes conformation change and alteration of the intramolecular
      interaction between TMR and bases of aptamer, leading to variance of fluorescence
      anisotropy (FA) of TMR, so direct FA analyis of cocaine is achieved.

PMID- 28429064
TI  - Simple and cost-effective liquid chromatography-mass spectrometry method to
      measure dabrafenib quantitatively and six metabolites semi-quantitatively in
      human plasma.
AB  - Dabrafenib is an inhibitor of BRAF V600E used for treating metastatic melanoma
      but a majority of patients experience adverse effects. Methods to measure the
      levels of dabrafenib and major metabolites during treatment are needed to allow
      development of individualized dosing strategies to reduce the burden of such
      adverse events. In this study, an LC-MS/MS method capable of measuring dabrafenib
      quantitatively and six metabolites semi-quantitatively is presented. The method
      is fully validated with regard to dabrafenib in human plasma in the range 5-5000
      ng/mL. The analytes were separated on a C18 column after protein precipitation
      and detected in positive electrospray ionization mode using a Xevo TQ triple
      quadrupole mass spectrometer. As no commercial reference standards are available,
      the calibration curve of dabrafenib was used for semi-quantification of
      dabrafenib metabolites. Compared to earlier methods the presented method
      represents a simpler and more cost-effective approach suitable for clinical
      studies. Graphical abstract Combined multi reaction monitoring transitions of
      dabrafenib and metabolites in a typical case sample.

PMID- 28429065
TI  - Rapid electrochemical quantification of Salmonella Pullorum and Salmonella
      Gallinarum based on glucose oxidase and antibody-modified silica nanoparticles.
AB  - In this article, a facile and sensitive electrochemical method for quantification
      of Salmonella Pullorum and Salmonella Gallinarum (S. Pullorum and S. Gallinarum)
      was established by monitoring glucose consumption with a personal glucose meter
      (PGM). Antibody-functionalized magnetic nanoparticles (IgG-MNPs) were used to
      capture and enrich S. Pullorum and S. Gallinarum, and IgG-MNPs-S. Pullorum and
      IgG-MNPs-S. Gallinarum complexes were magnetically separated from a sample using
      a permanent magnet. The trace tag was prepared by loading polyclonal antibodies
      and high-content glucose oxidase on amino-functionalized silica nanoparticles
      (IgG-SiNPs-GOx). With a sandwich-type immunoassay format, IgG-SiNPs-GOx were
      added into the above mixture solution and conjugated to the complexes, forming
      sandwich composites IgG-MNPs/S. Pullorum and S. Gallinarum/IgG-SiNPs-GOx. The
      above sandwich composites were dispersed in glucose solution. Before and after
      the hydrolysis of glucose, the concentration of glucose was measured using PGM.
      Under optimal conditions, a linear relationship between the decrease of glucose
      concentration and the logarithm of S. Pullorum and S. Gallinarum concentration
      was obtained in the concentration range from 1.27 * 102 to 1.27 * 105 CFU mL-1,
      with a detection limit of 7.2 * 101 CFU mL-1 (S/N = 3). This study provides a
      portable, low-cost, and quantitative analytical method for bacteria detection;
      thus, it has a great potential in the prevention of disease caused by S. Pullorum
      and S. Gallinarum in poultry. Graphical abstract A schematic illustration of the
      fabrication process of IgG-SiNPs-GOD nanomaterials (A) and IgG-MNPs (B) and
      experimental procedure of detection of S. Pullorum and S. Gallinarum using GOD
      functionalized silica nanospheres as trace tags based on PGM (C).

PMID- 28429066
TI  - Atmospheric pressure MALDI for the noninvasive characterization of carbonaceous
      ink from Renaissance documents.
AB  - The analytical methods that are usually applied to determine the compositions of
      inks from ancient manuscripts usually focus on inorganic components, as in the
      case of iron gall ink. In this work, we describe the use of atmospheric
      pressure/matrix-assisted laser desorption ionization-mass spectrometry (AP/MALDI
      MS) as a spatially resolved analytical technique for the study of the organic
      carbonaceous components of inks used in handwritten parts of ancient books for
      the first time. Large polycyclic aromatic hydrocarbons (L-PAH) were identified in
      situ in the ink of XVII century handwritten documents. We prove that it is
      possible to apply MALDI-MS as a suitable microdestructive diagnostic tool for
      analyzing samples in air at atmospheric pressure, thus simplifying investigations
      of the organic components of artistic and archaeological objects. The
      interpretation of the experimental MS results was supported by independent Raman
      spectroscopic investigations. Graphical abstract Atmospheric pressure/MALDI mass
      spectrometry detects in situ polycyclic aromatic hydrocarbons in the carbonaceous
      ink of XVII century manuscripts.

PMID- 28429067
TI  - Neuronal oscillations and synchronicity associated with gamma-hydroxybutyrate
      during resting-state in healthy male volunteers.
AB  - RATIONALE: Gamma-hydroxybutyrate (GHB) is a putative neurotransmitter, a drug of
      abuse, an anesthetic agent, and a treatment for neuropsychiatric disorders. In
      previous electroencephalography (EEG) studies, GHB was shown to induce an
      electrophysiological pattern of "paradoxical EEG-behavioral dissociation"
      characterized by increased delta and theta oscillations usually associated with
      sleep during awake states. However, no detailed source localization of these
      alterations and no connectivity analyses have been performed yet. OBJECTIVES AND
      METHODS: We tested the effects of GHB (20 and 35 mg/kg, p.o.) on current source
      density (CSD), lagged phase synchronization (LPS), and global omega complexity
      (GOC) of neuronal oscillations in a randomized, double-blind, placebo-controlled,
      balanced cross-over study in 19 healthy, male participants using exact low
      resolution electromagnetic tomography (eLORETA) of resting-state high-density EEG
      recordings. RESULTS: Compared to placebo, GHB increased CSD of theta oscillations
      (5-7 Hz) in the posterior cingulate cortex (PCC) and alpha1 (8-10 Hz)
      oscillations in the anterior cingulate cortex. Higher blood plasma values were
      associated with higher LPS values of delta (2-4 Hz) oscillations between the PCC
      and the right inferior parietal lobulus. Additionally, GHB decreased GOC of
      alpha1 oscillations. CONCLUSION: These findings indicate that alterations in
      neuronal oscillations in the PCC mediate the psychotropic effects of GHB. Theta
      oscillations emerging from the PCC in combination with stability of functional
      connectivity within the default mode network might explain the GHB-related
      "paradoxical EEG-behavioral dissociation." Our findings related to GOC suggest a
      reduced number of relatively independent neuronal processes, an effect that has
      also been demonstrated for other anesthetic agents.

PMID- 28429069
TI  - MuPeXI: prediction of neo-epitopes from tumor sequencing data.
AB  - Personalization of immunotherapies such as cancer vaccines and adoptive T cell
      therapy depends on identification of patient-specific neo-epitopes that can be
      specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a
      program to identify tumor-specific peptides and assess their potential to be neo
      epitopes. The program input is a file with somatic mutation calls, a list of HLA
      types, and optionally a gene expression profile. The output is a table with all
      tumor-specific peptides derived from nucleotide substitutions, insertions, and
      deletions, along with comprehensive annotation, including HLA binding and
      similarity to normal peptides. The peptides are sorted according to a priority
      score which is intended to roughly predict immunogenicity. We applied MuPeXI to
      three tumors for which predicted MHC-binding peptides had been screened for T
      cell reactivity, and found that MuPeXI was able to prioritize immunogenic
      peptides with an area under the curve of 0.63. Compared to other available tools,
      MuPeXI provides more information and is easier to use. MuPeXI is available as
      stand-alone software and as a web server at http://www.cbs.dtu.dk/services/MuPeXI
      .

PMID- 28429068
TI  - Nicotine deprivation elevates neural representation of smoking-related cues in
      object-sensitive visual cortex: a proof of concept study.
AB  - OBJECTIVE: In the current study, we use functional magnetic resonance imaging
      (fMRI) and multi-voxel pattern analysis (MVPA) to investigate whether tobacco
      addiction biases basic visual processing in favour of smoking-related images. We
      hypothesize that the neural representation of smoking-related stimuli in the
      lateral occipital complex (LOC) is elevated after a period of nicotine
      deprivation compared to a satiated state, but that this is not the case for
      object categories unrelated to smoking. METHODS: Current smokers (>=10 cigarettes
      a day) underwent two fMRI scanning sessions: one after 10 h of nicotine
      abstinence and the other one after smoking ad libitum. Regional blood oxygenated
      level-dependent (BOLD) response was measured while participants were presented
      with 24 blocks of 8 colour-matched pictures of cigarettes, pencils or chairs. The
      functional data of 10 participants were analysed through a pattern classification
      approach. RESULTS: In bilateral LOC clusters, the classifier was able to
      discriminate between patterns of activity elicited by visually similar smoking
      related (cigarettes) and neutral objects (pencils) above empirically estimated
      chance levels only during deprivation (mean = 61.0%, chance (permutations) =
      50.0%, p = .01) but not during satiation (mean = 53.5%, chance (permutations) =
      49.9%, ns.). For all other stimulus contrasts, there was no difference in
      discriminability between the deprived and satiated conditions. CONCLUSION: The
      discriminability between smoking and non-smoking visual objects was elevated in
      object-selective brain region LOC after a period of nicotine abstinence. This
      indicates that attention bias likely affects basic visual object processing.

PMID- 28429070
TI  - Properties of synchronous spontaneous Ca2+ transients in the mural cells of rat
      rectal arterioles.
AB  - Synchrony of spontaneous Ca2+ transients among venular mural cells (smooth muscle
      cells and pericytes) in visceral organs relies on the intercellular spread of L
      type voltage-dependent Ca2+ channel (LVDCC)-dependent depolarisations. However,
      the mechanisms underlying the synchrony of spontaneous Ca2+ transients between
      arteriolar mural cells are less understood. The spontaneous intracellular Ca2+
      dynamics of arteriolar mural cells in the rat rectal submucosa were visualised by
      Cal-520 Ca2+ imaging to analyse their synchrony. The mural cells in fine
      arterioles that had a rounded cell body with several extended processes developed
      spontaneous 'synchronous' Ca2+ transients arising from Ca2+ released from
      sarcoendoplasmic reticulum Ca2+ stores. Gap junction blockers (3 MUM
      carbenoxolone, 10 MUM 18beta-glycyrrhetinic acid), a Ca2+-activated Cl- channel
      (CaCC) blocker (100 MUM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) or
      lowering extracellular Cl- concentration (from 134.4 to 12.4 mM) disrupted the
      synchrony of Ca2+ transients between arteriolar mural cells. Blockers of T-type
      voltage-dependent Ca2+ channels (TVDCCs, 1 MUM mibefradil or ML218) or LVDCCs (1
      MUM nifedipine) reduced the Ca2+ transient frequency or their area under curve
      (AUC), respectively. However, neither TVDCC nor LVDCC blockers disrupted the
      synchrony of Ca2+ transients among arteriolar mural cells. This is in contrast
      with rectal venules in which nifedipine disrupted the synchrony of spontaneous
      Ca2+ transients. Thus, spontaneous transient depolarisations arising from the
      opening of CaCCs may effectively spread to neighbouring arteriolar mural cells
      via gap junctions to maintain the Ca2+ transient synchrony. Activation of TVDCCs
      appears to accelerate spontaneous Ca2+ transients, while LVDCCs predominantly
      contribute to the duration of Ca2+ transients.

PMID- 28429071
TI  - The surgical management of radiation proctopathy.
AB  - BACKGROUND: There is sparse evidence guiding the optimum surgical management of
      patients with radiation proctopathy (RP). The purpose of this review is to
      analyse all the literature on the surgical management of RP in order to guide
      physicians and surgeons as to when and what surgery should be employed for these
      patients. METHODS: A literature search of PubMed, EMBASE, MEDLINE, Ovid, and
      Cochrane Library using the MeSH terms "radiation proctopathy", "proctitis",
      "surgical management", and related terms as keywords was performed. The review
      included all articles that reported on the surgical management of patients with
      radiation proctopathy. All relevant articles were cross-referenced for further
      articles and any unavailable online were retrieved from hard-copy archive
      libraries. Eighteen studies including one prospective cohort study, fifteen
      retrospective cohort studies, and three small case series are included.
      CONCLUSION: Surgery is indicated for patients with RP for rectal obstruction,
      perforation, fistulae, or a failure of medical measures to control the symptoms
      of RP. Surgery centres mainly on diversion version resection. Diversion alone
      does not remove the damaged tissue leaving the patient at risk of continued
      complications including bleeding, perforation, occlusion, and abscess formation;
      however, major resectional surgery carries higher risks. Morbidity and mortality
      vary 0-44% and 0-11% for diversion only versus 0-100% and 0-14% for resectional
      surgery. There is no universally agreed surgical first-line approach. The data
      supports both resection with defunctioning stoma or diversion only as reasonable
      first-line surgical options for patients requiring surgery for RP.

PMID- 28429072
TI  - Kidney development and perspectives for organ engineering.
AB  - Organ transplantation is currently the best strategy for treating end stage renal
      disease (ESRD) but the numbers of donor kidneys available are not sufficient to
      meet the needs of the ever-increasing ESRD population. Therefore, developments in
      the field of tissue engineering are necessary to provide alternative treatments.
      Decellularization and three-dimensional (3D) bioprinting strategies may serve as
      attractive novel options. Since successful tissue engineering requires an in 
      depth understanding of organ development and regulatory pathways, we discuss
      signaling in renal development and the composition of the renal extracellular
      matrix before presenting progress in the decellularization and 3D bioprinting
      fields.

PMID- 28429073
TI  - Urinary extracellular vesicles. A promising shortcut to novel biomarker
      discoveries.
AB  - Proteomic and genomic techniques have reached full maturity and are providing
      unforeseen details for the comprehensive understanding of disease pathologies at
      a fraction of previous costs. However, for kidney diseases, many gaps in such
      information remain to inhibit major advances in the prevention, treatment and
      diagnostics of these devastating diseases, which have enormous global impact. The
      discovery of ubiquitous extracellular vesicles (EV) in all bodily fluids is
      rapidly increasing the fundamental knowledge of disease mechanisms and the ways
      in which cells communicate with distant locations in processes of cancer spread,
      immunological regulation, barrier functions and general modulation of cellular
      activity. In this review, we describe some of the most prominent research streams
      and findings utilizing urinary extracellular vesicles as highly versatile and
      dynamic tools with their extraordinary protein and small regulatory RNA species.
      While being a highly promising approach, the relatively young field of EV
      research suffers from a lack of adherence to strict standardization and carefully
      scrutinized methods for obtaining fully reproducible results. With the
      appropriate guidelines and standardization achieved, urine is foreseen as forming
      a unique, robust and easy route for determining accurate and personalized disease
      signatures and as providing highly useful early biomarkers of the disease
      pathology of the kidney and beyond.

PMID- 28429074
TI  - Ultrastructure of pheochromocytoma: undescribed morphologic features.
AB  - We examined samples of human pheochromocytoma from 11 patients aged 30-70 years
      including one case of malignant pheochromocytoma with a view to identifying
      previously unreported ultrastructural details.We identified two types of nuclear
      inclusions consisting of irregularly shaped singular or multiple granulofibrillar
      formations with a typical concentric halo, on the one hand, and accumulations of
      egg-shaped structures consisting of granules and microfilaments, on the other. In
      some of the tumor cells, membrane-covered inclusions containing parallel laminar
      elements arranged in a paracrystalline, periodic fashion, or mega-mitrochondriae
      characterized by increased electrodensity of their matrix, and fibrillary
      material in the spaces between the cristae were present. A frequent finding
      consisted of typical ciliary formations, while rough/smooth tubular aggregates of
      different size occurred less frequently. Finally, we were able to demonstrate the
      uptake of norepinephrine by smooth muscle fibers in the periphery of arterial
      vessels as evidenced by linear accumulations of membrane-covered granules
      separating bands of contractile smooth muscle components in the peripheral layers
      of arterial vessels close to norepinephrine producing neoplastic cells.These
      findings represent ultrastructural features that contribute to further
      elucidating the ultrastructural characteristics of the human pheochromocytoma.

PMID- 28429075
TI  - Toward personalized management in bladder cancer: the promise of novel molecular
      taxonomy.
AB  - Empowered by the recent advances in next generation sequencing and bioinformatics
      technology, an unprecedented wave of integrated transcriptomic and genomic
      studies have impacted the field of bladder cancer. These studies not only have
      confirmed previously charted genetic pathways in bladder cancer development but
      also have led to the discovery of numerous additional crucial driver genetic
      alterations. As a result, a novel genomic-based taxonomy is emerging that
      promises to better define clinically relevant intrinsic subtypes of bladder
      cancer. The current review is an update on the above advances and their
      significant implications on the future of bladder cancer patient management.

PMID- 28429076
TI  - [Search for risk genes in schizophrenia].
AB  - BACKGROUND: Schizophrenia is a severe psychiatric disease affecting approximately
      0.5-1% of the general population. The relative contribution of genetic factors
      has been estimated to be 64-81%. OBJECTIVE: This review summarizes recent efforts
      to identify genetic variants associated with schizophrenia. METHODS: Relevant
      linkage and candidate genes as well as genome wide association studies, studies
      on copy number variants and next generation sequencing are presented and
      discussed. RESULTS: The latest and worldwide largest study on the genetics of
      schizophrenia found 128 genome wide significant single nucleotide polymorphisms
      (SNP) and 108 genome wide loci. The most obvious association is with genetic
      variations in the major histocompatibility complex (MHC). Besides polymorphisms,
      structural variants in the form of copy number variants (CNV), such as
      microdeletions and microduplications have a very high impact in a subgroup of
      patients. These CNVs are mainly microdeletions on 1q21.1, 2p16.3, 3q29, 15q13.3
      and 16p11.2 as well as a large deletion on 22q11.21 and a microduplication on
      16p11.2. CONCLUSION: A large new body of evidence on the genetics of
      schizophrenia is expected through next generation sequencing approaches. Future
      studies will particularly address the functional characterization of genetic
      variants.

PMID- 28429077
TI  - [Implementation of the German S3 guidelines on dementia in clinical practice:
      wish or reality?]
AB  - BACKGROUND: Published in 2009, the German S3 guidelines on dementia define a
      milestone in quality improvement of the diagnostics and treatment of dementia. In
      clinical practice patients suffering from dementia are primarily treated by
      physicians in private practice; therefore, this study examined how the guidelines
      are implemented in outpatient clinical settings. Furthermore, it aimed at the
      identification of behavioral determinants that govern the actual diagnostic and
      therapeutic approach in clinical practice. METHODS: Physicians involved in the
      primary care of dementia patients were asked to participate in a nationwide
      internet survey. The questionnaire covered aspects on the diagnostic and
      therapeutic care of dementia patients as recommended by the S3 guidelines.
      Behavioral determinants of the implementation of the guidelines (e. g. treatment
      decisions) were derived from an established psychological prediction model.
      RESULTS: Out of a total of 2755 physicians contacted, the data of 225
      participants could be used in this study. The diagnostic recommendations of the
      S3 guidelines were implemented in satisfactory measures (e.g. combined cognitive
      screening in at least 68%, cerebral neuroimaging in at least 93% and specific
      laboratory diagnostics in at least 27% of cases); however, only two thirds of the
      patients with indications for a guideline-conform therapy were treated in
      accordance with the S3 guidelines. There was a substantial prescription of non
      recommended drugs and a notable long-term use of antipsychotic drugs
      (prescription by at least 14% of non-neurological medical specialists and by 8%
      of neurologists and psychiatrists). When considering the behavioral determinants
      in the implementation of the guidelines, normative assumptions ("my colleagues
      and patients expect me to comply with the guidelines") surprisingly had the
      highest impact, which was then followed by attitudes towards the behavior
      ("utilization of the guidelines improves diagnostics and therapy"). CONCLUSION:
      The German S3 guidelines on dementia were satisfactorily implemented in
      outpatient clinical practice; however, deficits existed in the frequency of the
      pharmaceutical treatment of patients with indications for therapy, the
      prescription of non-recommended drugs and the relatively common use of permanent
      neuroleptic medications. Interestingly, the motivation for implementation of the
      guidelines was not primarily influenced by the physicians' personal convictions
      but mainly stimulated by the expectations of others.

PMID- 28429078
TI  - [Telephone coaching for depression].
AB  - BACKGROUND: Depression is associated with a substantial utilization of resources
      in the German healthcare system. A typical symptom in depression is loss of
      drive, which possibly contributes to non-adherence and increased costs.
      OBJECTIVE: The study is based on routine healthcare data and tested the
      hypothesis that telephone coaching in cases of depression leads to a reduction in
      total healthcare costs. MATERIAL AND METHODS: Based on approximately 80
      covariates and using propensity score matching, a total of 1586 persons who had
      received telephone coaching for depression and covered by a German statutory
      health insurance fund were matched to a comparable cohort of patients with
      depression to whom telephone coaching had not been provided. RESULTS: Within the
      study period of 12 months (3rd quarter 2012-4th quarter 2013) a positive program
      effect was observed for the intervention group by a significant reduction of
      total healthcare costs (2332 ? vs. 2626 ?, p = 0.0015) resulting in total savings
      to the statutory health insurance fund of 415,532 ?. Investment costs amounted to
      256,683.42 ? leading to a return on investment of 1.62 ? (total savings/total
      investment). The coaching program was well accepted by patients. CONCLUSION:
      Telephone coaching for depression was able to significantly reduce total
      healthcare expenditure and the intervention was well accepted by patients.

PMID- 28429079
TI  - The R2R3-MYB TT2b and the bHLH TT8 genes are the major regulators of
      proanthocyanidin biosynthesis in the leaves of Lotus species.
AB  - MAIN CONCLUSION: By exploiting interspecific hybrids and their progeny, we
      identified key regulatory and transporter genes intimately related to
      proanthocyanidin biosynthesis in leaves of Lotus spp. Proanthocyanidins (PAs),
      known as condensed tannins, are polymeric flavonoids enriching forage legumes of
      key nutritional value to prevent bloating in ruminant animals. Unfortunately,
      major forage legumes such as alfalfa and clovers lack PAs in edible tissues.
      Therefore, engineering the PA trait in herbage of forage legumes is paramount to
      improve both ecological and economical sustainability of cattle production
      system. Progresses on the understanding of genetic determinants controlling PA
      biosynthesis and accumulation have been mainly made studying mutants of
      Arabidopsis, Medicago truncatula and Lotus japonicus, model species unable to
      synthesize PAs in the leaves. Here, we exploited interspecific hybrids between
      Lotus corniculatus, with high levels of PAs in the leaves, and Lotus tenuis, with
      no PAs in these organs, and relative F2 progeny, to identify among candidate PA
      regulators and transporters the genes mainly affecting this trait. We found that
      the levels of leaf PAs significantly correlate with the expression of MATE1, the
      putative transporter of glycosylated PA monomers, and, among the candidate
      regulatory genes, with the expression of the MYB genes TT2a, TT2b and MYB14 and
      the bHLH gene TT8. The expression levels of TT2b and TT8 also correlated with
      those of all key structural genes of the PA pathways investigated, MATE1
      included. Our study unveils a different involvement of the three Lotus TT2
      paralogs to the PA trait and highlights differences in the regulation of this
      trait in our Lotus genotypes with respect to model species. This information
      opens new avenues for breeding bloat safe forage legumes.

PMID- 28429080
TI  - Effect of GPR84 deletion on obesity and diabetes development in mice fed long
      chain or medium chain fatty acid rich diets.
AB  - PURPOSE: Although there is good evidence showing that diets rich in medium chain
      fatty acids (MCFAs) have less marked obesogenic and diabetogenic effects than
      diets rich in long chain fatty acids (LCFAs), the role of the pro-inflammatory,
      medium chain fatty acid receptor (GPR84) in the aetiology of obesity and glucose
      intolerance is not well characterised. We set out to determine whether GPR84
      expression influences obesity and glucose intolerance susceptibility in MCFA and
      LCFA rich diet fed mice. METHODS: Wild type (WT) and GPR84 knockout (KO) mice
      were fed a control, MCFA or LCFA diet, and body mass, heart, liver and epididymal
      fat mass was assessed, as well as glucose tolerance and adipocyte size. RESULTS:
      LCFA diets increased body mass and decreased glucose tolerance in both WT and
      GPR84 KO animals while MCFA diets had no effect on these parameters. There were
      no differences in body weight when comparing WT and GPR84 KO mice on the
      respective diets. Glucose tolerance was also similar in WT and GPR84 KO mice
      irrespective of diet. Liver mass was increased following LCFA feeding in WT but
      not GPR84 KO mice. Hepatic triglyceride content was increased in GPR84 KO animals
      fed MCFA, and myocardial triglyceride content was increased in GPR84 KO animals
      fed LCFA. CONCLUSIONS: GPR84 deletion had no effects on body weight or glucose
      tolerance in mice fed either a high MCFA or LCFA diet. GPR84 may influence lipid
      metabolism, as GPR84 KO mice had smaller livers and increased myocardial
      triglyceride accumulation when fed LCFA diets, and increased liver triglyceride
      accumulation in responses to increased dietary MCFAs.

PMID- 28429081
TI  - Cognitive and mood improvements following acute supplementation with purple grape
      juice in healthy young adults.
AB  - PURPOSE: Berry-derived phenolic compounds found in grapes have been associated
      with a number of health benefits, including the augmentation of human brain
      function and cognition. Previous intervention studies of Concord grape juice have
      demonstrated improvement to memory and driving ability following 3- to 4-month
      supplementation in middle-aged and older adults. However, no studies to date have
      demonstrated acute cognitive benefits of grape juice, and investigation of these
      effects in young adults is lacking. METHODS: This randomised, placebo-controlled,
      double-blind, counterbalanced-crossover study, assessed the effects of 230 ml
      purple grape juice or sugar-matched control in 20 healthy young adults.
      Computerised measures of episodic memory, working memory, attention and mood were
      completed at baseline and following a 20-min absorption period. RESULTS: Purple
      grape juice significantly improved reaction time on a composite attention measure
      (p = 0.047) and increased calm ratings (p = 0.046) when compared to placebo.
      Order effects also indicated an enduring positive effect on pre-dose memory
      reaction time (p = 0.018) and post-dose calm ratings (p = 0.019) when purple
      grape was consumed first. CONCLUSIONS: These findings in a small sample of
      healthy young adults suggest that purple grape juice can acutely enhance aspects
      of cognition and mood. No significant effects of juice were observed on memory
      measures, suggesting that these may be less susceptible to manipulation following
      acute supplementation in healthy young adults. Potential mechanisms underlying
      these effects include modulation of cerebral blood flow, glucoregulation and
      inhibition of monoamine oxidase activity, all of which require further
      exploration.

PMID- 28429082
TI  - The effect of a combined thoracic and soft-tissue trauma on blood flow and tissue
      formation in fracture healing in rats.
AB  - INTRODUCTION: Previously, it was found that fracture healing is impaired by blunt
      chest trauma and an additional soft-tissue trauma. The mechanisms leading to this
      disturbance are largely unknown. Here, we investigated the effect of thoracic and
      soft-tissue trauma on blood flow of the injured lower leg and on tissue
      differentiation and callus formation during fracture healing. MATERIALS AND
      METHODS: Male Wistar rats received either a mid-shaft fracture of the tibia alone
      (group A), an additional chest trauma (group B), or additional chest and soft
      tissue traumas (group C). Peripheral blood flow was determined by Laser Doppler
      Flowmetry before and after the injury, and on observation days 1, 3, 7, 14, and
      28. Quantitative histological analysis was performed to assess callus size and
      composition. RESULTS: All groups displayed an initial decrease in blood flow
      during the first 3 days post-trauma. A recovery of the blood flow that even
      exceeded preoperative levels occurred in group A and later and to a lesser degree
      in group B, but not in group C. The amount of callus formation decreased with
      increasing trauma load. More cartilage was formed after 7 days in groups B and C
      than in group A. At later healing time points, callus composition did not differ
      significantly. CONCLUSIONS: An increasing injury burden causes a decreasing blood
      supply capacity and revascularization, and leads to impaired callus formation and
      an increasing delay in bone healing.

PMID- 28429083
TI  - Intravenous treprostinil infusion via a fully implantable pump for pulmonary
      arterial hypertension.
AB  - OBJECTIVES: Parenteral prostanoids infused via external pumps are well
      established pulmonary arterial hypertension (PAH) treatments. However, local side
      effects and systemic infections restrict their use. The purpose of this study was
      to investigate the safety of a fully implantable treprostinil infusion pump
      (LENUS Pro(r)) in patients with PAH. METHODS: Thirty patients with PAH undergoing
      pump implantation (with stable PAH therapy for >=3 weeks pre-implantation) were
      included in this prospective, multicenter, observational study (NCT01979822).
      Primary endpoints were predefined adverse events (AEs) during implantation, in
      hospital and/or during 6-month follow-up. Refill-related AEs were a secondary
      endpoint. RESULTS: Twenty-nine patients completed 6-month follow-up (one
      underwent lung transplantation). During implantation, one pneumothorax (not
      requiring drainage) occurred. Four patients had an in-hospital AE (including one
      catheter revision). During 6-month follow-up, AEs were most frequent at the first
      refill (10); the most common AE was seroma around the pump. No infections
      occurred. One pump required replacement because of a defective septum caused by
      use of a non-approved refill needle (associated with extravasation). Apart from
      the extravasation, no refill-related AEs were recorded. Post hoc efficacy
      analyses showed significant improvements in functional class [number in
      functional class I/II/III/IV: 0/5/21/2 (baseline) versus 3/8/17/0 (6 months); p =
      0.012] and 6-min walk distance (mean +/- standard deviation: 407 +/- 122 m versus
      445 +/- 127 m; n = 17; p = 0.014). CONCLUSIONS: This study supports use of a
      fully implantable treprostinil infusion pump in patients with PAH requiring
      parenteral prostanoids. Refills should be performed by specialized healthcare
      professionals at patients' homes or at experienced centers using approved
      equipment.

PMID- 28429084
TI  - Rs4878104 contributes to Alzheimer's disease risk and regulates DAPK1 gene
      expression.
AB  - In 2006, a candidate gene study reported death-associated protein kinase 1
      (DAPK1) rs4878104 variant to be significantly associated with Alzheimer's disease
      (AD) risk. However, the following studies showed inconsistent association
      results. Here, we conducted an updated analysis to investigate the potential
      association between rs4878104 and AD using a total of 60,751 samples (20,161 AD
      cases and 40,590 controls). In the pooled population, the results based on the
      allele and genotype genetic models show that rs4878104 variant is not
      significantly associated with AD risk. Interestingly, we identified rs4878104
      variant to be significantly associated with AD risk in American population and
      Chinese population in subgroup analysis. Using multiple large-scale expression
      quantitative trait loci datasets, we further found that rs4878104 T allele could
      significantly regulate increased DAPK1 expression in European population. These
      findings suggest that rs4878104 may contribute AD susceptibility by modifying
      DAPK1 expression in European population.

PMID- 28429086
TI  - Comment to: Should we perform elective inguinal hernia repair in the elderly? Wu
      J. J. et al.

PMID- 28429085
TI  - The role of RNA alternative splicing in regulating cancer metabolism.
AB  - Tumor cells alter their metabolism by a wide array of mechanisms to promote
      growth and proliferation. Dysregulated expression and/or somatic mutations of key
      components of the glycolytic pathway/TCA cycle as well as other metabolic
      pathways allow tumor cells to improve their ability to survive harsh conditions
      such as hypoxia and the presence of reactive oxygen species, as well as the
      ability to obtain nutrients to increase lipids, protein, and nucleic acids
      biogenesis. Approximately 95% of the human protein encoding genes undergo
      alternative splicing (AS), a regulated process of gene expression that greatly
      diversifies the proteome by creating multiple proteins from a single gene. In
      recent years, a growing body of evidence suggests that unbalanced AS, the
      formation of certain pro-tumorigenic isoforms and the reduction of anti
      tumorigenic isoforms, is implicated in a variety of cancers. It is becoming
      increasingly clear that cancer-associated AS contributes to increased growth and
      proliferation, partially due to effects on metabolic reprogramming. Here, we
      summarize the known roles of AS in regulating cancer metabolism. We present
      evidence supporting the idea that AS, in many types of cancer, acts as a
      molecular switch that alters metabolism to drive tumorigenesis. We propose that
      the elucidation of misregulated AS and its downstream effects on cancer
      metabolism emphasizes the need for new therapeutic approaches aiming to modulate
      the splicing machinery to selectively target cancer cells.

PMID- 28429087
TI  - The 'AbdoMAN': an artificial abdominal wall simulator for biomechanical studies
      on laparotomy closure techniques.
AB  - PURPOSE: Incisional hernia remains a frequent complication after abdominal
      surgery associated with significant morbidity and high costs. Animal and clinical
      studies have exhibited some limitations. The purpose of this study was to develop
      an artificial human abdominal wall (AW) simulator in order to enable
      investigations on closure modalities. We hypothesized that a physical model of
      the human AW would give new insight into commonly used suture techniques
      representing a substantial complement or alternative to clinical and animal
      studies. METHODS: The 'AbdoMAN' was developed to simulate human AW biomechanics.
      The 'AbdoMAN' capacities include measurement and regulation of intra-abdominal
      pressure (IAP), generation of IAP peaks as a result of muscle contraction and
      measurements of AW strain patterns analyzed with 3D image stereo correlation
      software. Intact synthetic samples were used to test repeatability. A laparotomy
      closure was then performed on five samples to analyze strain patterns. RESULTS:
      The 'AbdoMAN' was capable of simulating physiological conditions. AbdoMAN lateral
      muscles contract at 660 N, leading the IAP to increase up to 74.9 mmHg (range
      65.3-88.3). Two strain criteria were used to assess test repeatability. A test
      with laparotomy closure demonstrated closure testing repeatability. CONCLUSIONS:
      The 'AbdoMAN' reveals as a promising enabling tool for investigating AW surgery
      related biomechanics and could become an alternative to animal and clinical
      studies. 3D image correlation analysis should bring new insights on laparotomy
      closure research. The next step will consist in evaluating different closure
      modalities on synthetic, porcine and human AW.

PMID- 28429088
TI  - An SNP panel for the analysis of paternally inherited alleles in maternal plasma
      using ion Torrent PGM.
AB  - Researchers have sought to develop an effective protocol for paternity analysis
      using cell-free DNA (cfDNA) in maternal plasma. The use of massively parallel
      sequencing (MPS) technology for SNP testing is attractive because of its high
      throughput capacity and resolution to single-base precision. In this study, we
      designed a customized SNP panel for cfDNA sequencing that includes 720 short
      amplicons (< 140 bp) targeting SNPs on the autosome and Y chromosome. The
      systemic performance was evaluated using the Ion Torrent PGM, indicating balanced
      coverage among most of the included loci, except for 78 poorly performing SNPs
      that were observed to have an inconsistent allele balance, lower coverage reads
      or high background signals. Then, the custom panel was used to perform cfDNA
      genotyping in maternal plasma from 20 pregnancies in the first and second
      trimesters (9 to 21 weeks). By establishing an allele fraction cutoff of 2.0%, 53
      to 128 autosomal SNP loci were considered informative for paternal origin.
      Validation results in foetal samples showed that 49.43% to 100% of the real
      paternal alleles were accurately identified, with incorrect alleles encountered
      in 3 cases. The concentration of foetal cfDNA ranged from 4.28% to 10.70%. Our
      results show that this amplicon-based sequencing strategy could be utilized in
      analysing paternally inherited alleles in maternal plasma. However, further
      studies and optimization are required for a more detailed and accurate
      interpretation of the cfDNA sequencing results based on MPS technology.

PMID- 28429089
TI  - The Effectiveness of Prophylactic Modified Neck Dissection for Reducing the
      Development of Lymph Node Recurrence of Papillary Thyroid Carcinoma.
AB  - AIM: The most frequent recurrence site of papillary thyroid carcinoma (PTC) is
      the cervical lymph nodes. The introduction of an electric linear probe for use
      with ultrasonography in 1996 improved preoperative lateral neck evaluations.
      Before 2006, however, our hospital routinely performed prophylactic modified neck
      dissection (p-MND) for N0 or N1a PTCs >1 cm to prevent node recurrence. In 2006,
      we changed our policy and the indications for p-MND to PTCs >3 cm and/or with
      significant extrathyroid extension. Here, we retrospectively compared lymph node
      recurrence-free survival between PTCs with/without p-MND. METHODS: We examined
      the cases of N0 or N1 and M0 PTC patients who underwent initial surgery in 1992
      2012. To compare lymph node recurrence-free survival between patients who did/did
      not undergo p-MND, we divided these patients into three groups (excluding those
      whose surgery was in 2006): the 2045 patients whose surgery was performed in 1992
      1996 (Group 1), the 2989 with surgery between 1997 (post-introduction of
      ultrasound electric linear probes) and 2005 (Group 2), and the 5332 operated on
      in 2007-2012 (Group 3). RESULTS: The p-MND performance rate of Group 3 (9%) was
      much lower than that of Group 1 (80%), but the lymph node recurrence-free
      survival of the former was significantly better, probably due to differences in
      clinical features and neck evaluations by ultrasound between the two groups. Our
      analysis of the patients aged <75 years with 1.1-4-cm PTCs in Groups 2 and 3
      showed that p-MND did not improve lymph node recurrence-free survival. p-MND did
      significantly improve lymph node recurrence-free survival for the extrathyroid
      extension-positive 3.1-4-cm PTCs, but not for the other subsets. CONCLUSIONS:
      Abolishing routine p-MND for PTCs in 2006 did not decrease lymph node recurrence
      free survival, probably due to improved ultrasound preoperative neck evaluations
      and clinical feature changes. Selective p-MND for high-risk cases improved lymph
      node recurrence-free survival.

PMID- 28429090
TI  - Impact of Angiotensin Receptor Blocker Use on Overall Survival Among Patients
      Undergoing Resection for Pancreatic Cancer.
AB  - BACKGROUND: Pancreatic cancer has higher concentrations of angiotensin II
      compared with other cancers. This study sought to assess the effect of
      angiotensin II receptor blockers (ARBs) on survival of patients undergoing
      resection using a large, nationally representative dataset. METHODS: Patients
      undergoing pancreatic cancer resection were identified in the Truven Health
      MarketScan database. Multivariable Cox proportional hazards regression was used
      to assess the effect of ARB use on overall survival. RESULTS: A total of 4299
      patients were identified, among whom 479 (11.1%) filled a prescription for an
      ARB. Mean patient age was 54.5 years (SD = 8.6 years); 2187 (51.1%) were female.
      Exactly 49.4% (n = 2125) of patients had a Charlson comorbidity index >2 at the
      time of surgery (n = 2125, 49.4%) and 59.6% (n = 2563) underwent a
      pancreaticoduodenectomy. Kaplan-Meier estimates of survival at 1, 2, and 4 years
      were 62.8% (95% CI: 61.3-64.2%), 38.2% (95% CI: 36.6-39.8%), and 19.0% (95% CI:
      17.1-21.0%), respectively. On multivariable analysis, ARB use was associated with
      a 24% decreased risk of death over the 5-year period in which patients were under
      observation (HR = 0.76, 95% CI: 0.67-0.87, p < 0.001). CONCLUSIONS: ARB use was
      associated with improved survival in patients undergoing resection of pancreatic
      cancer. Further research is required into the differential effect of ARBs in the
      treatment of pancreatic cancer.

PMID- 28429091
TI  - The Impact of Healthcare Privatization on Access to Surgical Care:
      Cholecystectomy as a Model: Reply.

PMID- 28429092
TI  - Natural History of MEN1 GEP-NET: Single-Center Experience After a Long Follow-Up.
AB  - BACKGROUND: The multiple endocrine neoplasia type 1 syndrome (MEN1) natural
      history is poorly evaluated, and few single-institution experiences about
      hereditary gastroenteropancreatic neuroendocrine tumors (GEP-NET) are reported.
      Our purpose is to analyze the role of GEP-NET in MEN1-related death, as well as
      the behavior of these lesions during follow-up. METHODS: The study population
      consists of 77 patients diagnosed with MEN1 GEP-NET, regularly followed up since
      1990. Extensive clinical data were prospectively recorded. Statistical analysis
      was performed both on the whole population of 77 patients and on two subgroups
      including patients who, during the long lasting study period, underwent GEP-NET
      surgery (50 pts) and who did not (27 pts), respectively. RESULTS: Twenty-five
      males (32.5%) and 52 females (67.5%) were enrolled. Sixty-four patients had MEN1
      family history (83.1%), and genetic mutation was detected in 67 cases (87%). The
      mean age at GEP-NET diagnosis was 41.4 years (SD = 13.6); 16 patients (20.8%) had
      GEP-NET diagnosed before age 30 and 12 cases (15.6%) before 1996. The mean
      interval time between MEN1 diagnosis and GEP-NET detection was 5.7 years (range 
      11/37; SD = 8.1 years). Overall, the mean follow-up time from MEN1 diagnosis was
      15.8 years (SD = 9.7 years) and from GEP-NET diagnosis was 9.6 years (SD = 6.9
      years). Gastrinoma was the most frequent functioning GEP-NET and
      pancreatoduodenectomy the most adopted surgery. GEP-NET progression affected 12
      patients within the non-surgical group, while 18 subjects developed progression
      after surgery. CONCLUSIONS: Our single-center data provide information on
      epidemiologic, clinical and pathological features of GEP-NET in MEN1 making
      possible to clarify their natural history.

PMID- 28429093
TI  - A case of glioblastoma resected immediately after administering bevacizumab:
      consideration on histopathological findings and safety of surgery.
AB  - Surgery after administering bevacizumab should be carefully considered
      particularly because of wound healing concerns. A 27-year-old man presented with
      multiple tumor recurrences after gross total removal of a left temporal
      oligodendroglioma (1p/19q-noncodeleted). Whole brain radiotherapy with
      concomitant temozolomide and bevacizumab was immediately prescribed; however, the
      patient's condition deteriorated because of brain herniation. Three days after
      administering bevacizumab, an emergency tumor removal with external decompression
      and a ventriculo-peritoneal shunt was performed. The surgery and postoperative
      clinical course were uneventful. On histopathological examination, the tumor
      showed findings such as tumor vessel thrombosis, numerous interstitial red blood
      cells, and cells with degraded, fragmented nuclei possibly suggesting apoptosis,
      which could be attributable to bevacizumab. Performing craniotomy shortly after
      administering bevacizumab is not recommended; however, it can still be safely
      performed as long as surgery and wound management is carefully performed. Vessel
      thrombosis might be among the mechanisms of action of bevacizumab.

PMID- 28429095
TI  - Pigeons (Columba livia) show change blindness in a color-change detection task.
AB  - Change blindness is a phenomenon whereby changes to a stimulus are more likely go
      unnoticed under certain circumstances. Pigeons learned a change detection task,
      in which they observed sequential stimulus displays consisting of individual
      colors back-projected onto three response keys. The color of one response key
      changed during each sequence and pecks to the key that displayed the change were
      reinforced. Pigeons showed a change blindness effect, in that change detection
      accuracy was worse when there was an inter-stimulus interval interrupting the
      transition between consecutive stimulus displays. Birds successfully transferred
      to stimulus displays involving novel colors, indicating that pigeons learned a
      general change detection rule. Furthermore, analysis of responses to specific
      color combinations showed that pigeons could detect changes involving both
      spectral and non-spectral colors and that accuracy was better for changes
      involving greater differences in wavelength. These results build upon previous
      investigations of change blindness in both humans and pigeons and suggest that
      change blindness may be a general consequence of selective visual attention
      relevant to multiple species and stimulus dimensions.

PMID- 28429094
TI  - Prospective evaluation of scrotal ultrasound and intratesticular perfusion by
      color-coded duplex sonography (CCDS) in TESE patients with azoospermia.
AB  - PURPOSE: The objective of this study was to assess whether CCDS might improve the
      outcome of testicular sperm retrieval in patients with azoospermia. Furthermore,
      we evaluated potential sonographic alterations of the testis before and after
      trifocal and Micro-TESE. METHODS: 78 patients were enrolled prospectively: 24
      with obstructive azoospermia (OA) and 54 with non-obstructive azoospermia (NOA).
      31 of 54 patients in the NOA group had negative surgical sperm retrieval.
      Testicular volume, hormonal parameters and sonographical findings were compared
      before and after TESE. The spermatogenetic score was determined for all retrieval
      sites. CCDS was performed at the upper, middle and lower segment of the testis.
      Ultrasound parameters and peak systolic velocity (PSV) were measured pre- and
      post-operatively. RESULTS: Testicular volume and epididymal head size were
      significantly increased in OA patients compared to NOA patients. Ultrasound
      parameters were comparable between NOA patients with and without successful sperm
      retrieval. A higher intratesticular PSV was significantly correlated with a
      better spermatogenic score in the corresponding sonographic position. However,
      after adjustment for other clinical confounders, PSV does not show a significant
      influence on the spermatogenic score. Testicular volume decreased significantly
      in all patients post-operatively after 6 weeks (p < 0.001). Finally, the PSV
      significantly increased in all patients 24 h after surgery and nearly returned to
      baseline levels after 6 weeks (p < 0.001). CONCLUSIONS: A higher intratesticular
      PSV may be helpful as a pre-operative diagnostic parameter in mapping for better
      sperm retrieval, but CCDS does not help to predict successful testicular sperm
      retrieval after adjustment for other clinical confounders.

PMID- 28429096
TI  - Differences in problem-solving between canid populations: Do domestication and
      lifetime experience affect persistence?
AB  - Past research has suggested that a variety of factors, phylogenetic and
      ontogenetic, play a role in how canines behave during problem-solving tasks and
      the degree to which the presence of a human influences their problem-solving
      behaviour. While comparisons between socialized wolves and domestic dogs have
      commonly been used to tease apart these predictive factors, in many cases a
      single dog population, often pets, have been used for these comparisons. Less is
      understood about how different populations of dogs may behave when compared with
      wolves, or with each other, during an independent problem-solving task. This
      experiment compared the independent persistence of four populations of canines
      (two groups of pet domestic dogs, a group of free-ranging domestic dogs, and
      human-socialized wolves) on an independent problem-solving task in the presence
      of an on looking human. Results showed that wolves persisted the most at the task
      while free-ranging dogs persisted the least. Free-ranging dogs gazed at the human
      experimenter for the longest durations during the task. While further research is
      needed to understand why these differences exist, this study demonstrates that
      dogs, even those living outside human homes as scavengers, show comparatively low
      levels of persistence when confronted with a solvable task in the presence of a
      human as well as significantly greater duration of human-directed gaze when
      compared with wolves.

PMID- 28429098
TI  - Symptomatic menopausal transition and subsequent bipolar disorder among midlife
      women with major depression: a nationwide longitudinal study.
AB  - Previous studies suggested that menopausal transition played an important role in
      the clinical course of major depression and bipolar disorder. However, the role
      of symptomatic menopausal transition in diagnostic conversion from major
      depression to bipolar disorder was still unknown. Using the Taiwan National
      Health Insurance Research Database, 50,273 midlife women aged between 40 and 60
      years in 2002~2008 with major depression were enrolled in our study and divided
      into two subgroups based on the presence (n = 21,120) or absence (n = 29,153) of
      symptomatic menopausal transition. Subjects who had subsequent bipolar disorder
      during the follow-up were identified. Midlife women with major depression and
      symptomatic menopausal transition had a higher incidence of the diagnostic
      conversion to bipolar disorder (7.3 vs. 6.6%, p = 0.003) than those with major
      depression alone. Cox regression analysis after adjusting for demographic data
      and psychiatric comorbidities further showed that symptomatic menopausal
      transition was associated with an increased risk of developing bipolar disorder
      (HR 1.14, 95% CI 1.07~1.23) among midlife women with major depression.
      Sensitivity test after excluding the 1-year and 3-year observation exhibited the
      consistent findings (HR 1.18, 95% CI 1.09~1.28; HR 1.20, 95% CI 1.08~1.34).
      Midlife women with the dual diagnoses of major depression and symptomatic
      menopausal transition had an increased risk of the diagnostic conversion to
      bipolar disorder compared to those with major depression alone. Further studies
      may be required to investigate the underlying mechanisms among menopausal
      transition and the diagnostic conversion from major depression to bipolar
      disorder.

PMID- 28429099
TI  - Anxiety, depression, and quality of life in mothers of newborns with microcephaly
      and presumed congenital Zika virus infection: a follow-up study during the first
      year after birth.

PMID- 28429097
TI  - Immunomodulatory and therapeutic role of Cinnamomum verum extracts in collagen
      induced arthritic BALB/c mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum verum (CV), also known as 'Dalchini',
      is the dry bark of the Cinnamomum verum (L.) plant, and has been used as a
      traditional Pakistani medicine to alleviate pain and inflammation in patients
      suffering from arthritic rheumatism. It contains alkaloids, triterpenes,
      Cinnamaldehyde and other volatile oils. The aim of the present study was to
      investigate the underlying biological effect of ethyl alcohol (EtOH) and methyl
      alcohol (MeOH) extracts from CV on collagen type-II induced arthritic (CIA) mice.
      MATERIALS AND METHODS: Gas chromatography mass spectrophotometry was used to
      perform fingerprinting identification of the EtOH and MeOH extracts. CIA mice
      model was established by subdermal injections of type-II bovine collagen (CII) on
      the 1st, 8th and 14th day of the experiment. Ethyl alcohol extract and methyl
      alcohol extract (1 mg/KgBW, 2 mg/KgBW and 4 mg/KgBW), was orally administered
      from the 15th day onwards for 2 weeks. Progression of oedema and joint
      inflammation was measured in the paws using a digital Vernier calliper every 3
      days from day 1 till the end of the experiment. The oxidative scavenging ability
      of cinnamaldehyde was evaluated using a DPPH assay. Similarly, the nitrogen free
      radical (NOS) production of isolated lymphocytes was evaluated using Greiss's
      method. The spleen index was calculated and knee joint changes were observed by
      histopathological sectioning. Western blot analysis was performed on peripheral
      blood derived serum for CII, CAPN1, TNFalpha and NFATc3. RESULTS: Extracts were
      shown to be enriched in trans-cinnamaldehyde and its analogues. Extracts showed
      good ameliorative effects (p < 0.05) after day 2 of treatment. A greater
      therapeutic role was observed for the 4 mg/kgBW dosage of the methanolic extract
      (p < 0.01). Swelling in the spleen was greatly reduced along with the generation
      of free radicals by lymphocytes, post treatment. There was also an inhibitory
      role by the extracts on NFATc3 (p < 0.05), TNF-Alpha (p < 0.05), CAII (p < 0.05)
      and mCalpain (p < 0.05) all proteins involved in RA. CONCLUSION: In this study,
      it has been demonstrated that administration of CV has a therapeutic potential on
      CIA. The data suggest that CV could have a potential role in the treatment of RA
      patients.

PMID- 28429100
TI  - Conversion of hormone and HER-2 receptor in metachronous neck metastases from
      breast carcinoma.
AB  - PURPOSE: Metastases are a common event in breast cancer. The expression of
      estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth
      factor receptor 2 (HER-2) is essential for therapy and prognosis, and their
      conversion during disease progression potentially affects the treatment regimen.
      The aim was to analyze the estrogen, progesterone and HER-2 receptor expression
      in primary tumors and metachronous neck metastases from patients with breast
      cancer. METHODS: A retrospective analysis of 27 patients with breast cancer and
      metachronous neck metastasis was performed. Distribution of neck metastasis to
      the neck levels and estrogen, progesterone and HER-2 receptor expression in
      primary tumor and metastasis were examined. RESULTS: The most common localization
      of neck metastasis was level V. ER, PR, and HER-2 in primary tumors were positive
      in 48.1, 51.9, and 26.3% of patients, respectively. A loss of ER and PR in neck
      metastasis was observed in 22.2 and 40.7% of the patients, respectively. HER-2
      change was present in 4 of 19 paired samples (21.0%). CONCLUSIONS: The expression
      of ER, PR and HER-2 in neck metastases can be expected to diverge from the
      expression of these markers in the primary tumor. As such changes can occur
      during disease progression, the evaluation of biomarkers in metastatic sites
      should be mandatory, whenever possible, to ensure that patients are receiving the
      most effective treatment at all times.

PMID- 28429101
TI  - Human circulating and tissue gastric cancer stem cells display distinct
      epithelial-mesenchymal features and behaviors.
AB  - INTRODUCTION: Metastasis is a leading cause of cancer-related-deaths worldwide.
      Recently, cancer stem cells (CSCs) have been believed to be responsible for tumor
      initiation and metastasis, but till now, difference of cellular features and
      behaviors between CSCs from tumor tissues (TCSCs) and circulation (CCSCs) remains
      largely unknown, which hinders the progression of targeted therapies for
      metastasis. METHODS AND RESULTS: Here, we provide the features of circulating
      gastric cancer stem cells (CGCSCs) isolated from human gastric adenocarcinoma.
      The CGCSCs and TGCSCs were culture in a same serum free stem cell culture medium,
      however the morphology are different with each other. EMT-associated markers were
      measured by Immunofluorescence, Western Blotting, and RT-PCR methods, and the
      results indicated that the CGCSCs and TGCSCs carry different epithelial
      mesenchymal features. And then, proliferation and apoptosis assays revealed that
      the CGCSCs exhibited characteristics of higher proliferation and resistance to
      apoptosis in vitro. Soft agar assay and nude mice tumorigenicity assay displayed
      strong tumorigenicity of CGCSCs. Finally, Matrigel invasion assays and in vivo
      experimental metastasis assay were also performed, which demonstrated that CGCSCs
      carry high invasive and metastatic capabilities than TGCSCs. CONCLUSIONS: As
      expected, the CGCSCs indeed showed extremely invasive and metastatic properties.
      They also exhibited distinctive mesenchymal phenotypes, high self-renewal,
      proliferative capabilities, tumor induction and low apoptosis. Interestingly,
      CGCSCs show small cell-size than TGCSCs (tissue gastric cancer stem cells). The
      findings might help us to understand the biological characteristic of CGCSCs
      deeply, and give light to strategies for cancer therapies.

PMID- 28429102
TI  - Improved systemic treatment for early breast cancer improves cure rates, modifies
      metastatic pattern and shortens post-metastatic survival: 35-year results from
      the Munich Cancer Registry.
AB  - PURPOSE: Systemic therapies (ATHs) in early breast cancer have improved the
      survival of breast cancer (BC) patients in recent decades. The magnitude of the
      changes in overall, metastasis-free (MFS) and post-metastatic (PMS) survival and
      in the metastasis (MET) pattern will be described. PATIENT AND METHODS: We
      analysed 60,227 patients with a diagnosis of T-N-M0 BC between 1978 and 2013 and
      11,983 patients with metastases (MET) in the Munich Cancer Registry. Patients
      will be divided into four time periods to identify relationships between BC and
      METs. Survival was estimated using Kaplan-Meier curves, and Cox proportional
      hazards models were used to explore the impact of the BC subtype and MET status
      on survival with the time periods as surrogate markers for ATH evolution.
      RESULTS: During the observation period, 5-year relative survival has improved
      from 80.3 to 93.6% with an adjusted hazard ratio of 0.54 (P < 0.0001). Successful
      implementation of ATH has changed the MET pattern. The percentage of liver and
      CNS METs has more than doubled, the rate of lung METs remains stable, and the
      rate of bone METs has been reduced by approximately 50%. MFS has been prolonged
      with a hazard ratio 0.75 (P < 0.0001), but PMS has declined (hazard ratio 1.36; P
      < 0.0001); however, effects of adjuvant and palliative treatments cannot be
      separated. These results do not contradict improvements in advanced BC and do not
      suggest alterations of MET tumour biology by ATH. CONCLUSIONS: Over the past
      three decades, ATHs have dramatically improved patient survival after BC
      diagnosis-most likely, by eradicating prevalent micro-METs; as a result, the MET
      pattern has changed. Eradicating only a portion of the first METs results in
      delaying the onset of subsequent MET, which leads to an apparently paradoxical
      effect: an extension of the MET-free interval and a reduction in PMS.

PMID- 28429103
TI  - Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome.
AB  - PURPOSE: Patients with 22q11.2 deletion syndrome have a variable decrease in
      immunological parameters, especially regarding T cell counts. The aim of this
      study was to investigate immunological change over time and factors associated
      with immunological recovery among patients with 22q11.2 deletion syndrome.
      METHODS: Patients with 22q11.2 deletion syndrome diagnosed by fluorescence in
      situ hybridization (FISH) were studied. Immunological parameters were evaluated
      every 6 months until patients returned to normal. Infection and vaccination
      histories were recorded and analyzed, and Kaplan-Meier survival curves were
      plotted to describe resolution of immunodeficiency. RESULTS: Forty-nine patients
      with an age range of 4 to 222 months were included. Twenty-five (51%) patients
      were female. In hypocalcemia, the odds ratio for CD4 lymphopenia was 17.03 (95%CI
      1.82-159.23; p value = 0.01). Thirty patients (61.2%) exhibited decreased CD4+ T
      cell numbers, which returned to normal level in 18 (60%) patients. Median age of
      CD4+ T cell resolution was 2.5 years. T cell functions were abnormal in three
      patients. T cell functions returned to normal in all patients at a median age of
      1.1 years. Six patients (13.5%) had abnormal serum immunoglobulin levels, with
      levels improving in four patients at 1.4 years of age. The most common infection
      was pneumonia (69.4%). BCG vaccination was administered in 47 of 49 patients at
      birth. Among 32 patients who had T cell defect, one patient developed BCGitis and
      one developed disseminated BCG. CONCLUSION: Immunodeficiencies identified among
      patients with 22q11.2 deletion syndrome were T cell defect (65.3%) and decreased
      immunoglobulin levels (12.2%). Median age of CD4 resolution was 2.5 years.

PMID- 28429104
TI  - Paecilomyces formosus Infection in an Adult Patient with Undiagnosed Chronic
      Granulomatous Disease.

PMID- 28429105
TI  - Increased expression of uPA, uPAR, and PAI-1 in psoriatic skin and in basal cell
      carcinomas.
AB  - There is substantial evidence implicating the urokinase system in tissue
      remodeling during neo-vascularization, inflammation, tumor invasion, and
      metastasis. Regulated degradation of the extracellular matrix at the leading edge
      of migrating cells, mediated by uPA and uPAR, is required for tissue remodeling,
      invasiveness, and angiogenesis. Psoriasis and basal cell carcinoma (BCC) are the
      most common skin diseases. Pathogenesis of both of them is associated with
      keratinocyte hyperproliferation, inflammatory cell migration, and angiogenesis
      processes in which the plasminogen system (uPA, uPAR, tPA, and PAI-1) plays a
      crucial role. In the present study, the comparative analysis of uPA, uPAR, tPA,
      and PAI-1 expression in the normal skin, in the biopsies of patients with
      psoriasis vulgaris, and BCC was carried out. uPA, uPAR, and PAI-1 expression was
      up-regulated in the epidermis of psoriatic skin and in tumor cells in BCC.
      Increased uPAR expression was detected in the derma of psoriatic lesions and in
      the stroma surrounding tumor cells in BCC. Increased expression of uPA in
      epidermal cells in psoriasis and in tumor cells in BCC suggests an important role
      of the uPA system for aggressively proliferating and invading cells of epidermal
      origin. A possible activation of the stroma, as a result of uPA-uPAR interaction
      between tumor cells and the surrounding stroma, is suggested.

PMID- 28429106
TI  - Occupational exposure to extremely low-frequency magnetic fields and risk for
      central nervous system disease: an update of a Danish cohort study among utility
      workers.
AB  - PURPOSE: Evidence of whether exposure to extremely low-frequency magnetic fields
      (ELF-MF) is related to central nervous system diseases is inconsistent. This
      study updates a previous study of the incidence of such diseases in a large
      cohort of Danish utility workers by almost doubling the period of follow-up.
      METHODS: We investigated the risks for dementia, motor neurone disease, Parkinson
      disease, multiple sclerosis and epilepsy among 32,006 men employed at the 99
      utility companies that supplied Denmark with electricity during the period 1900
      1993. Cases were identified in the Danish National Patient Registry and the
      cohort was followed during 1982-2010. Exposure was estimated from a job-exposure
      matrix based on company records of job title and area of work and cohort members
      were allocated to one of three categories (<0.1, 0.1-0.99 and >=1.0 uT). RESULTS:
      For dementia, multiple sclerosis and epilepsy the incidence rate ratios (IRR)
      were close to unity, but higher for motor neurone disease [IRR 1.24, 95%
      confidence interval (CI) 0.86-1.79] and lower for Parkinson disease (IRR 0.81,
      95% CI 0.67-0.97) among workers exposed to >=0.1 uT compared with the Danish
      population. For the highest level of exposure (>=1.0 uT), IRRs of 1.44, 1.78,
      1.40 and 1.34 were observed for dementia, motor neurone disease, multiple
      sclerosis and epilepsy, respectively. CONCLUSIONS: We observed elevated risks of
      dementia, motor neurone disease, multiple sclerosis and epilepsy and lower risks
      of Parkinson disease in relation to exposure to ELF-MF in a large cohort of
      utility employees.

PMID- 28429107
TI  - Psychosocial factors at work and sleep problems: a longitudinal study of the
      general working population in Norway.
AB  - PURPOSE: A growing number of longitudinal studies report associations between
      adverse psychosocial factors at work and sleep problems. However, the evidence
      regarding the direction of these associations and the effects of changes in
      exposure across time is limited. This study examined the plausibility of normal,
      reverse, and reciprocal associations between ten psychosocial factors at work and
      sleep problems. In addition, we analyzed if reduced exposure across time had the
      anticipated result of reducing the risk of sleep problems. METHODS: Randomly
      drawn from the general working-age population, the cohort comprised respondents
      with an active employee relationship in 2009 and 2013 (N = 5760). Exposures and
      outcome were measured on two occasions separated by 4 years. We computed several
      sex-stratified logistic regression models with adjustments for various plausible
      confounders. RESULTS: We found support for the commonly hypothesized
      unidirectional forward associations between psychosocial factors at work and
      sleep problems among women only. Among men, psychosocial stressors at work and
      sleep problems were reciprocally and reversely related. Nevertheless, reduced
      exposure levels across time pertaining to effort-reward imbalance (OR = 0.36; 95%
      CI = 0.19-0.69) and lack of social support (OR = 0.55; 95% CI = 0.32-0.93) among
      men, and work-family imbalance (OR = 0.26; 95% CI = 0.15-0.46) among women were
      associated with a robust significant lower risk of sleep problems compared to
      those in the stable high exposure groups. CONCLUSIONS: The study results suggest
      that preventive measures targeting effort-reward imbalance and lack of social
      support among men, and work-family imbalance among women, might contribute to
      reduce the risk of troubled sleep among employees.

PMID- 28429108
TI  - Phenetic and phylogenetic relationships among Aceria spp. (Acari: Eriophyoidea)
      inhabiting species within the family Brassicaceae in Serbia.
AB  - We examined morphological and genetic differences among Aceria spp. inhabiting
      six Brassicaceae species in Serbia. Five of them have been already mentioned in
      the literature as original or alternate hosts of Aceria spp. (Berteroa incana
      (L.) DC., Capsella bursa-pastoris (L.) Medik., Cardamine hirsuta L., Lepidium
      draba L. and Sisymbrium orientale L.), whereas Aurinia petraea (Ard.) Schur was
      registered here for the first time as a host for Aceria sp. Results of
      morphometric analyses indicated clear differentiation of Aceria spp. from B.
      incana, L. draba, A. petraea and S. orientale, whereas the other two entities
      were less diverse and clustered together. Molecular analyses indicated that the
      average mean divergence over all sequence pairs was 18.3% (11.8-25.9%) and
      disclosed that the observed mtCOI distances between the six host-associated
      Aceria entities are large enough to represent differences between species. The
      Aceria sp. hosted by B. incana was morphologically and genetically most
      distinctive, whereas discrepancy between phenetic and phylogenetic relationships
      was found in the position of Aceria sp. hosted by L. draba when compared with
      those inhabiting C. hirsuta, S. orientale and C. bursa-pastoris.

PMID- 28429109
TI  - Associations of maximal voluntary isometric hip extension torque with muscle size
      of hamstring and gluteus maximus and intra-abdominal pressure.
AB  - PURPOSE: Muscle size of the hamstring and gluteus maximus (GM) as well as intra
      abdominal pressure (IAP) are considered as factors affecting the torque
      development during hip extension. This study examined the associations of torque
      development during maximal voluntary isometric hip extension with IAP and muscle
      size of the hamstring and GM. METHODS: Anatomical cross-sectional area (ACSA) of
      the hamstring and thickness of GM were determined in 20 healthy young males using
      an ultrasonography apparatus (Experiment 1). Torque and IAP were simultaneously
      measured while subjects performed maximal voluntary isometric hip extension. The
      IAP was measured using a pressure transducer placed in the rectum and determined
      at the time at which the developed torque reached to the maximal. In Experiment
      2, torque and IAP were measured during maximal voluntary isometric hip flexion in
      18 healthy young males. RESULTS: The maximal hip extension torque was
      significantly correlated with the IAP (r = 0.504, P = 0.024), not with the ACSA
      of the hamstring (r = 0.307, P = 0.188) or the thickness of GM (r = 0.405, P =
      0.076). The relationship was still significant even when the ACSA of the
      hamstring and the thickness of GM were adjusted statistically (r = 0.486, P =
      0.041). The maximal hip flexion torque was not significantly correlated with the
      IAP (r = -0.118, P = 0.642). CONCLUSION: The current results suggest that IAP can
      contribute independently of the muscle size of the agonists to maximal voluntary
      hip extension torque.

PMID- 28429110
TI  - Inhibition of the CRF1 receptor influences the activity of antidepressant drugs
      in the forced swim test in rats.
AB  - Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and impairment of
      the central corticotropin-releasing factor (CRF) system are factors in the
      pathogenesis of depression. Though several antagonists of the CRF1 receptor were
      effective in the recognized behavioral tests for antidepressant activity, there
      is still little information on the potential interactions between CRF1 receptor
      inhibitors and conventional antidepressant therapy. The aim of our study was to
      assess the influence of SN003, a CRF1 receptor blocker, on the activity of
      imipramine and fluoxetine in the forced swim test (FST) in rats which presented
      some signs of depression. The experiments were carried out on female Wistar rats
      subjected to 14-day subcutaneous corticosterone (CORT) administration (20
      mg/kg/day). The antidepressant-like effect was determined by the FST and the CRF
      levels in the hypothalamus, amygdala, and peripheral blood were measured by a
      high-sensitivity immunoenzymatic test. SN003 (0.5 mg/kg) potentiated the
      antidepressant-like effect of imipramine (15 mg/kg) and fluoxetine (7.5 mg/kg).
      Moreover, the co-administration of the tested agents abolished CORT-induced
      increase in CRF levels in the examined biological material more profoundly than
      monotherapy. Our present findings give further evidence that the blockage of CRF
      action may be useful in the treatment of mood disorders. The concurrent use of
      well-known antidepressants with CRF1 receptor antagonists could be beneficial in
      terms of safety, since it requires lower doses of the applied agents.

PMID- 28429113
TI  - Response to letter to the editor: "is drug induced sedation endoscopy surgical
      decision making process objective and systematic?"

PMID- 28429111
TI  - Impact of serum albumin levels on long-term outcomes in patients undergoing
      percutaneous coronary intervention.
AB  - Epidemiological studies have demonstrated an association between low serum
      albumin levels and both coronary artery disease (CAD) and mortality. However, the
      long-term clinical impact of low serum albumin level in patients with CAD
      undergoing percutaneous coronary intervention (PCI) has not yet been fully
      investigated. We studied 2860 all-comer patients with CAD who underwent their
      first PCI and had data available for pre-procedural serum albumin between 2000
      and 2011. Patients were assigned to tertiles based on pre-procedural albumin
      levels. We evaluated the incidence of major adverse cardiac events (MACE),
      including all-cause death and nonfatal myocardial infarction. Mean albumin level
      was 4.0 +/- 0.5 g/dL. Lower albumin levels were associated with older age, lower
      body mass index (BMI), and higher prevalences of female sex, ACS and chronic
      kidney disease (CKD). During the median follow-up period of 7.4 years, Kaplan
      Meier curves showed ongoing divergence in rates of MACE among albumin tertiles
      (albumin <3.8 g/dl: 44.3% vs. 3.8-4.1 g/dl: 38.0% vs. >4.1 g/dl: 22.9%; log-rank
      p < 0.0001). After adjusting for established cardiovascular risk factors
      including age, acute coronary syndrome, BMI and CKD, serum albumin levels were
      significantly associated with incidence of MACE (HR 1.74 per 1-g/dl decrease, 95%
      CI 1.34-2.26, p < 0.0001) and all-cause mortality (HR 1.74, 95% CI 1.30-2.33, p =
      0.0002). Pre-PCI low serum albumin level was associated with worse long-term
      outcomes, independent of traditional risk factors. Assessing albumin levels may
      allow risk stratification in patients with CAD undergoing PCI.

PMID- 28429112
TI  - Testicular cancer patients undergoing cisplatin based chemotherapy exhibit
      temporary olfactory threshold scores changes.
AB  - Testicular cancer is the most frequent malignant disease in young males between
      15 and 35 years. Platinum based chemotherapy regimen is the therapy of choice in
      advanced disease. This treatment has also adverse effects caused by the
      cytostatic active substances, such as olfactory dysfunctions. The aim of this
      study was, therefore, to monitor olfactory function of testicular cancer patients
      during and 6 months after chemotherapy. A total of 17 patients (mean age 31.06 +/
      10.26 years), which underwent chemotherapy (mean 2.47 cycles +/- 0.5) were
      enrolled in this study. Odor threshold, discrimination and identification were
      assessed by means of the "Sniffin' Sticks" prior to and on day 42, 90 and 180
      after chemotherapy has been completed. Furthermore, patients' ratings of
      olfactory function and depressive symptoms were evaluated. Threshold scores were
      significantly lower on day 90 (8.0 +/- 2.51) compared to baseline (10.4 +/- 2.20)
      (p = 0.014) and recovered almost completely on day 180 (9.65 +/- 3.26). Odor
      discrimination and identification did not show significant changes during
      therapy. The decrease of the olfactory function during/immediately after
      chemotherapy was underlined by the subjectively perceived impaired olfactory
      function during this time. In addition almost every fourth patient presented with
      a depressed mood at the beginning of chemotherapy. Patients should be informed
      about possible transient olfactory impairment during/immediately after
      chemotherapy.

PMID- 28429114
TI  - Physical and chemical characteristics of the longissimus dorsi from swine reared
      in climate-controlled and uncontrolled environments.
AB  - The aim of this study was to evaluate the effect of ambient temperature on the
      physical and chemical characteristics of the longissimus dorsi muscle by
      comparing the quality of meat from pigs reared in a controlled and in an
      uncontrolled environment, the latter provided with a shallow pool. Twenty
      castrated male pigs of the Topigs line were randomly allotted to two treatments:
      a controlled environment, with constant temperature (22  degrees C) and relative
      humidity (70%); and an uncontrolled environment in a conventional shed for
      rearing pigs equipped with a shallow pool, where pigs were subject to climatic
      variations. Meat from pigs kept in the controlled environment showed a greater
      capacity to retain intracellular water, higher tenderness, and lower cholesterol
      levels than meat from pigs reared in the uncontrolled environment, but displayed
      higher lipid oxidation and a lower concentration of DHA. Treatments had no effect
      on color, pH, chemical composition, or fatty acid profile (except DHA
      concentration). Rearing pigs in sheds equipped with a shallow pool minimizes the
      effects of environmental heat on meat quality, allowing the production of high
      quality meat in warm climate regions without expensive investments. Animals
      reared in an uncontrolled environment equipped with a shallow pool are able to
      produce meat with characteristics within the quality standards and with similar
      quality to that of meat from animals raised in controlled environment.

PMID- 28429115
TI  - Comparison of the tolerability of newly introduced childhood vaccines in the
      Netherlands.
AB  - : In 2011, the 7-valent conjugated pneumococcal vaccine (PCV7) was replaced by
      the 10-valent vaccine (PCV10) and universal hepatitis B vaccination has been
      introduced in the Netherlands. A questionnaire study was conducted to assess the
      tolerability of DTaP-IPV-Hib + PCV7 (PCV7-cohort), DTaP-IPV-Hib + PCV10 (PCV10
      cohort), and DTaP-IPV-Hib-HepB + PCV10 (HepB-cohort). Parents were asked to
      report in questionnaires local reactions and systemic adverse events (AEs) before
      and after vaccination of their infant at 2, 3, 4, and 11 months of age. For 29.0
      and 29.4% infants of the PCV7-cohort, at least one local reaction was reported in
      the week after the first dose of DTaP-IPV (left leg) and PCV-7 vaccination (right
      leg). Significantly more infants from the PCV10-cohort (45.1%, p < 0.001 and
      44.6%, p < 0.001) and HepB-cohort (42.6%, p < 0.001 and 41.9%, p < 0.001)
      reported at least one local reaction. This effect was less pronounced after the
      successive doses. Most of the infants experienced at least one systemic AE, and
      after dose 4, this was higher for infants in the PCV10-cohort (65.9%, p = 0.047)
      and HepB-cohort (70.6%, p = 0.000) compared to the PCV7-cohort (62.3%).
      CONCLUSION: Addition of antigens to a vaccine resulted in a higher
      reactogenicity, but the AEs were in general mild and transient. What is Known: *
      Assessment of adverse events is crucial for achieving the highest safety in
      immunization programs, in order to inform public health actions and maintain
      public confidence in immunization programs. What is New: * Newly introduced
      vaccines DTaP-IPV-Hib-HepB and PCV10 are generally safe and well tolerated in
      infants. * These results are useful for information purposes and for monitoring
      variations in rates of AEs in the general population or in the target group over
      time.

PMID- 28429116
TI  - Dutch national immunization schedule: compliance and associated characteristics
      for the primary series.
AB  - : In the Netherlands, the recommended priming immunization schedule for
      diphtheria, tetanus, pertussis and polio (DTaP-IPV) is at 2, 3 and 4 months of
      age. We evaluated the compliance with the recommended schedule, as well as its
      characteristics. We included all infants born between 2007 and 2012 who received
      minimally one DTaP-IPV vaccination (n = 1,061,578). Infants complied with the
      schedule if they received the first vaccination between 6 and 9 weeks of age, and
      the second and third vaccination 2-6 weeks after the first and second
      vaccination. We examined associations between compliance and several
      characteristics using log-binomial regression. Compliance for the first, second
      and third vaccination was 81.6, 88.3 and 84.2%, respectively. Compliance with the
      total recommended schedule was 64.5%, and increased from 60.1% for 2007 to 68.5%
      for 2012. Compliance was higher for full-term infants (65.9%), infants with
      normal birth weight (66.0%) and when both parents were born in the Netherlands
      (66.8%). CONCLUSION: Delayed vaccination during the primary vaccination schedule
      occurs in one sixth of the Dutch children. Efforts to improve compliance should
      be focused in particular on preterm infants, infants with low birth weight and
      infants whose parents are not born in the Netherlands. What is Known: * A delayed
      start of vaccination leads to a longer period at risk for infectious diseases,
      e.g. pertussis * Delayed vaccination is associated with several factors including
      prematurity, low birth weight, family size, birth order, low socioeconomic status
      and health status of the child What is New: * Compliance with the recommended
      priming immunization schedule for diphtheria, tetanus, pertussis and polio was
      64.5%, and increased from 60.1% for 2007 to 68.5% for 2012 * If the first
      vaccination was delayed, there was a higher chance that the following
      vaccinations were administered 'out-of-schedule' as well, resulting in even a
      higher age at second and third vaccination.

PMID- 28429117
TI  - A comparison of McGrath MAC(r) and standard direct laryngoscopy in simulated
      immobilized cervical spine pediatric intubation: a manikin study.
AB  - : Emergency airway management in children is generally considered to be
      challenging, and endotracheal intubation requires a high level of personal skills
      and experience. Immobilization of the cervical spine is indicated in all patients
      with the risk of any cervical spine injury but significantly aggravates
      endotracheal intubation. The best airway device in this setting has not been
      established yet, although the use of videolaryngoscopes is generally promising.
      Seventy-five moderately experienced paramedics of the Emergency Medical Service
      of Poland performed endotracheal intubations in a pediatric manikin in three
      airway scenarios: (A) normal airway, (B) manual in-line cervical immobilization,
      and (C) cervical immobilization using a Patriot cervical extrication collar and
      using two airway techniques: (1) McGrath videolaryngoscope and (2) Macintosh
      blade in a randomized sequence. First-attempt intubation success rate, time to
      intubation, glottis visualization, and subjective ease of intubation were
      investigated in this study. Intubation of difficult airways, including manual in
      line and cervical collar immobilization, using the McGrath was significantly
      faster, with a higher first-attempt intubation success rate, better glottic
      visualization, and ease of intubation, compared to Macintosh-guided intubation.
      In the normal airway, both airway techniques performed equal. CONCLUSION: Our
      manikin study indicates that the McGrath may be a reasonable first intubation
      technique option for endotracheal intubation in difficult pediatric emergencies.
      Further clinical studies are therefore indicated. What is known : * Airway
      management in pediatrics is challenging and requires a high level of skills and
      experience. Cervical immobilization is indicated in all patients with any risk of
      cervical spine injury, but it significantly aggravates endotracheal intubation in
      these patients. Videolaryngoscopes have been reported to ease intubation and
      provide better airway visualization in the regular clinical setting. What is new:
      * The McGrath is an easy-to-use and clinically often used videolaryngoscope, but
      it has never been investigated in pediatrics with an immobilized cervical spine.
      In the normal airway, the McGrath provided better airway visualization compared
      to Macintosh laryngoscopy. However, better visualization did not lead to
      decreased time to intubation and a higher success rate of the first intubation
      attempt. In difficult airways, the McGrath provided better airway visualization
      and this led to faster intubation, a higher first-attempt intubation success
      rate, and better ease of intubation compared to Macintosh-guided intubation.

PMID- 28429118
TI  - [How frequent are poor prognostic markers in rheumatoid arthritis? : An estimate
      based on three epidemiologic cohorts].
AB  - BACKGROUND: Unfavorable prognostic factors-high disease activity, early erosions,
      and autoantibodies-should be considered when making treatment decisions in
      rheumatoid arthritis (RA). There are little data on the frequency of individual
      poor prognostic factors among RA patients in daily care. METHODS: Disease
      activity (Disease Activity Score, DAS28), erosions, antibodies against
      citrullinated peptides or rheumatoid factor (ACPA/RF+), previous treatment
      failure, inflammation markers, and functional disability (FFbH < 70) were defined
      as prognostic factors. Different treatment decision making situations were
      evaluated in disease-modifying antirheumatic drug (DMARD)-naive patients from the
      early RA CAPEA cohort (n = 1059), and in patients from the biologics register
      RABBIT after failure of one (n = 2217) or more (n = 3280) conventional synthetic
      (cs)DMARDs or one (n = 1134) or more (n = 795) biologic (b)DMARDs. With the
      national database of German arthritis centers (NDB), the frequency of these
      factors was analyzed according to treatment strata (no/1st/2nd/3rd DMARD; n =
      5707). RESULTS: In DMARD-naive patients (CAPEA), 50% presented with DAS28 > 5.1,
      64% were ACPA/RF+, 13% had erosions, and 37% functional disability (FFbH < 70).
      In RABBIT, 63 (1st csDMARD failure) to 81% (>=2 bDMARD failures) were ACPA/RF+,
      29 to 70% had erosions, 33 to 52% DAS28 > 5.1, and 41 to 66% had FFbH < 70,
      respectively. In the NDB, between 47 (DMARD-naive) and 82% (>=2 previous DMARDs)
      were ACPA/RF+, 5 to 11%, had high disease activity under treatment (DAS28 > 5.1),
      and 26 to 50% had functional disability (FFbH < 70), respectively. CONCLUSION:
      With growing numbers of previous DMARD therapies, increasing proportions of
      patients have poor prognostic factors. This underlines the importance of these
      factors for a difficult-to-treat disease course.

PMID- 28429119
TI  - Single-port hysterectomy: robotic versus laparoscopic.
AB  - This study evaluated the feasibility and safety of robotic single port
      hysterectomy and laparoscopic single port hysterectomy, and to compare the
      perioperative parameters of the two systems. Twenty patients underwent robotic
      single port hysterectomy and 25 patients underwent laparoscopic single port
      hysterectomy. All hysterectomies were successfully performed via a single port
      and there were no conversions to conventional multi-port laparoscopy, multi-port
      robotic, open surgery, or vaginal surgery. The median operative time and
      hysterectomy time in robotic and laparoscopic groups were 90 vs. 90 min (P 0.74),
      57.5 vs. 60 min (P 0.17), respectively. The median estimated blood loss was 40 ml
      in the robotic group and 50 ml in the laparoscopic group (P 0.77). No operative
      and post-operative complications were observed in the two groups. The median time
      to discharge from the hospital was one day for both techniques (P 0.17). Robotic
      and laparoscopic single port systems are feasible and safe for hysterectomy
      operation in terms of operative time, conversion to laparotomy or multiport
      laparoscopy/robotic rates, complication rates, and postoperative results in the
      hands of experienced surgeons. The possible benefits of robotic single port
      surgery compared with conventional laparoscopy should be evaluated in further
      randomized controlled studies.

PMID- 28429120
TI  - The influence of pump rotation speed on hemodynamics and myocardial oxygen
      metabolism in left ventricular assist device support with aortic valve
      regurgitation.
AB  - Aortic valve regurgitation (AR) is a serious complication under left ventricular
      assist device (LVAD) support. AR causes LVAD-left ventricular (LV) recirculation,
      which makes it difficult to continue LVAD support. However, the hemodynamics and
      myocardial oxygen metabolism of LVAD support with AR have not been clarified,
      especially, how pump rotation speed influences them. An animal model of LVAD with
      AR was newly developed, and how pump rotation speed influences hemodynamics and
      myocardial oxygen metabolism was examined in acute animal experiments. Five goats
      (55 +/- 9.3 kg) underwent centrifugal type LVAD, EVAHEART implantation. The AR
      model was established by placing a vena cava filter in the aortic valve.
      Hemodynamic values and the myocardial oxygen consumption, delivery, and oxygen
      extraction ratio (O2ER) were evaluated with changing pump rotation speeds with or
      without AR (AR+, AR-). AR+ was defined as Sellers classification 3 or greater. AR
      was successfully induced in five goats. Diastolic aortic pressure was
      significantly lower in AR+ than AR- (p = 0.026). Central venous pressure, mean
      left atrial pressure, and diastolic left ventricular pressure were significantly
      higher in AR+ than AR- (p = 0.010, 0.047, and 0.0083, respectively). Although
      systemic flow did not improve with increasing pump rotation speed, LVAD pump flow
      increased over systemic flow in AR+, which meant increasing pump rotation speed
      increased LVAD-LV recirculation and did not contribute to effective systemic
      circulation. O2ER in AR- decreased with increasing pump rotation speed, but O2ER
      in AR+ was hard to decrease. The O2ER in AR+ correlated positively with the flow
      rate of LVAD-LV recirculation (p = 0.012). AR caused LVAD-LV recirculation that
      interfered with the cardiac assistance of LVAD support and made it ineffective to
      manage with high pump rotation speed.

PMID- 28429121
TI  - Renovascular hypertension: results in adulthood of renal autotransplantation
      performed in children.
AB  - BACKGROUND: This study describes the long-term results of renal
      autotransplantation for renovascular hypertension performed in children who are
      now 21 years of age or older. METHODS: Sixteen children (4 boys, 12 girls) with a
      mean age of 11.2 years at the time of the procedure underwent ex-vivo surgery at
      the university hospital of Saint-Etienne between 1992 and 2008. Acetylsalicylic
      acid was used for antiplatelet therapy in the postoperative period, without
      routine anticoagulation. The mean follow-up period was 15 years. The clinical
      course of these patients was retrospectively reviewed in adulthood and the
      results analyzed. RESULTS: The children were treated with a mean of 2.37 drugs
      per patient, and the mean preoperative blood pressure of the entire patient
      population was 151/89 mmHg. Mean preoperative creatinine clearance was 80
      ml/min/1.73 m2. There was no postoperative death. One patient experienced a
      thrombosis immediately after the surgery, leading to a redo surgery. In this
      patient diuresis was restarted, but without efficient concentration and
      filtration, ultimately leading the patient to have a renal transplant after 1
      year. At the end of the follow-up period, eight of the 16 patients (50%) were
      cured and the others were improved. At the last follow-up the mean blood pressure
      was 127/70 mmHg, and the mean number of drugs per patient was 0.68. The mean
      creatinine clearance at last follow-up was 104.3 ml/min/1.73 m2. Three patients
      had secondary procedures, with two undergoing percutaneous angioplasty (at
      postoperative months 9 and 12, respectively) and one having an hepatorenal bypass
      at postoperative year 4. Primary patency was 12/16 (75%); primary assisted
      patency was 15/16 (94%); secondary patency was 16/16 (100%). CONCLUSION: This
      study shows that renal autotransplantation has good and stable long-term results
      and is an effective conservative strategy for treating renovascular hypertension
      in children, thus avoiding nephrectomy.

PMID- 28429122
TI  - Quantifying Golgi structure using EM: combining volume-SEM and stereology for
      higher throughput.
AB  - Investigating organelles such as the Golgi complex depends increasingly on high
      throughput quantitative morphological analyses from multiple experimental or
      genetic conditions. Light microscopy (LM) has been an effective tool for
      screening but fails to reveal fine details of Golgi structures such as vesicles,
      tubules and cisternae. Electron microscopy (EM) has sufficient resolution but
      traditional transmission EM (TEM) methods are slow and inefficient. Newer volume
      scanning EM (volume-SEM) methods now have the potential to speed up 3D analysis
      by automated sectioning and imaging. However, they produce large arrays of
      sections and/or images, which require labour-intensive 3D reconstruction for
      quantitation on limited cell numbers. Here, we show that the information storage,
      digital waste and workload involved in using volume-SEM can be reduced
      substantially using sampling-based stereology. Using the Golgi as an example, we
      describe how Golgi populations can be sensed quantitatively using single random
      slices and how accurate quantitative structural data on Golgi organelles of
      individual cells can be obtained using only 5-10 sections/images taken from a
      volume-SEM series (thereby sensing population parameters and cell-cell
      variability). The approach will be useful in techniques such as correlative LM
      and EM (CLEM) where small samples of cells are treated and where there may be
      variable responses. For Golgi study, we outline a series of stereological
      estimators that are suited to these analyses and suggest workflows, which have
      the potential to enhance the speed and relevance of data acquisition in volume
      SEM.

PMID- 28429123
TI  - Optical coherence tomography angiography vessel density mapping at various
      retinal layers in healthy and normal tension glaucoma eyes.
AB  - PURPOSE: To investigate peripapillary vessel density at various spatial locations
      and layers in healthy and normal tension glaucoma eyes using optical coherence
      tomography angiography (OCTA). METHODS: A commercial OCTA device (AngioPlex; Carl
      Zeiss Meditec) was used to image microvasculature in a 6 * 6-mm optic disc
      region. Vessel densities of superficial and deep retinal layers were calculated
      using an automatic thresholding algorithm. Vessel density maps were plotted by
      averaging individual angiogram images. The spatial characteristics of vessel
      densities were analyzed at clock-hour sectors and in five 0.7-mm-thick concentric
      circles from a diameter of 2.0 to 5.5 mm. Areas under the receiver operating
      characteristics curves (AUCs) assessed the glaucoma diagnostic ability. RESULTS:
      Vessel density maps of superficial and deep retinal layers were significantly
      reduced at the 7 and 11 o'clock positions in glaucomatous eyes. In superficial
      layer, vessel density significantly decreased as the distance from the optic disc
      margin increased, except in the innermost circle (2.0-2.7-mm). There were
      significant differences in AUCs of superficial vessel density between innermost
      circle and the other outer circles. In the deep layer, the innermost circle
      showed significantly higher vessel density than the outer circles. Vessel density
      at 7 o'clock showed the best diagnostic performance (AUCs, 0.898 and 0.789) both
      in the superficial and deep layers. The innermost circle showed eccentric feature
      compared to the outer circles in terms of spatial characteristics and diagnostic
      ability. CONCLUSIONS: Understanding of the spatial characteristics of
      peripapillary vasculature may be helpful in clinical practice and determining the
      optimal measurement area of vessel density.

PMID- 28429124
TI  - How bumblebees use lateral and ventral optic flow cues for position control in
      environments of different proximity.
AB  - Flying insects frequently navigate through environments of different complexity.
      In this study, buff-tailed bumblebees (Bombus terrestris L.) were trained to fly
      along tunnels of different widths, from 60 to 240 cm. In tunnel widths of 60 and
      120 cm, bumblebees control their lateral position by balancing the magnitude of
      translational optic flow experienced in the lateral visual field of each eye. In
      wider tunnels, bumblebees use translational optic flow cues in the ventral visual
      field to control their lateral position and to steer along straight tracks. Our
      results also suggest that bumblebees prefer to fly over surfaces that provide
      strong ventral optic flow cues, rather than over featureless ones. Together,
      these strategies allow bumblebees to minimize the risk of collision and to
      maintain relatively straight flight paths in a broad range of environments.

PMID- 28429125
TI  - Low plasma homoarginine concentration is associated with high rates of all-cause
      mortality in renal transplant recipients.
AB  - In renal transplant recipients (RTR), we recently found that low urinary
      excretion of homoarginine (hArg) is associated with mortality and graft failure.
      However, it is not known whether such prospective associations also hold true for
      plasma concentrations of hArg. In the present study, we therefore determined
      plasma concentrations of hArg in the same cohort, i.e. in 687 RTR (functioning
      graft >=1 year), and in 140 healthy donors, before and after kidney donation.
      Plasma hArg concentrations were significantly lower in RTR compared to healthy
      controls [1.24 (0.95-1.63) uM vs. 1.58 (1.31-2.03) uM, P < 0.001], and kidney
      donation resulted in a decrease in plasma hArg concentration to 1.41 (1.10-1.81)
      uM (P < 0.001). In RTR, multivariable linear regression analysis revealed BMI
      (beta = 0.124), heart rate (beta = -0.091), pre-emptive transplantation (beta =
      0.078), antidiabetic medication (beta = -0.091), eGFR (beta = 0.272), plasma PTH
      (beta = -0.098), uric acid (beta = 0.137), alkaline phosphatase (beta = -0.100),
      HDL (beta = -0.111), NT-pro-BNP (beta = -0.166), and urinary urea excretion (beta
      = 0.139) as main determinants of plasma hArg (all P < 0.05). In RTR, plasma hArg
      concentration was inversely associated with all-cause [hazard ratio (HR) 0.59
      (95% CI 0.50-0.70), P < 0.001] and cardiovascular mortality [HR 0.50 (0.39-0.66),
      P < 0.001], both expressed per standard deviation change in log-transformed hArg,
      independent of potential confounders. To conclude, our results suggest that the
      kidney is a major hArg production site and an important modulator of hArg
      homeostasis in the renal and cardiovascular systems. Moreover, low plasma hArg is
      independently associated with increased risk of cardiovascular mortality in RTR,
      which corroborates the cardiovascular importance of preserving kidney function
      after transplantation.

PMID- 28429126
TI  - Assessing the Role of Place and Timing Cues in Coding Frequency and Amplitude
      Modulation as a Function of Age.
AB  - Natural sounds can be characterized by their fluctuations in amplitude and
      frequency. Ageing may affect sensitivity to some forms of fluctuations more than
      others. The present study used individual differences across a wide age range (20
      79 years) to test the hypothesis that slow-rate, low-carrier frequency modulation
      (FM) is coded by phase-locked auditory-nerve responses to temporal fine structure
      (TFS), whereas fast-rate FM is coded via rate-place (tonotopic) cues, based on
      amplitude modulation (AM) of the temporal envelope after cochlear filtering.
      Using a low (500 Hz) carrier frequency, diotic FM and AM detection thresholds
      were measured at slow (1 Hz) and fast (20 Hz) rates in 85 listeners. Frequency
      selectivity and TFS coding were assessed using forward masking patterns and
      interaural phase disparity tasks (slow dichotic FM), respectively. Comparable
      interaural level disparity tasks (slow and fast dichotic AM and fast dichotic FM)
      were measured to control for effects of binaural processing not specifically
      related to TFS coding. Thresholds in FM and AM tasks were correlated, even across
      tasks thought to use separate peripheral codes. Age was correlated with slow and
      fast FM thresholds in both diotic and dichotic conditions. The relationship
      between age and AM thresholds was generally not significant. Once accounting for
      AM sensitivity, only diotic slow-rate FM thresholds remained significantly
      correlated with age. Overall, results indicate stronger effects of age on FM than
      AM. However, because of similar effects for both slow and fast FM when not
      accounting for AM sensitivity, the effects cannot be unambiguously ascribed to
      TFS coding.

PMID- 28429127
TI  - Uveitis in Siriraj Hospital: pattern differences between immune-related uveitis
      and infectious uveitis in a university-based tertiary care hospital.
AB  - PURPOSE: To describe a proportion of uveitis and to analyse differences between
      immune-related uveitis and infectious uveitis groups. METHODS: A retrospective
      study of 458 uveitis patients were categorized into immune-related uveitis,
      infectious uveitis, masquerade, and undetermined groups. The pattern of
      inflammation was described. Subgroup analysis was performed to compare pattern
      differences between immune-related uveitis and infectious uveitis groups.
      RESULTS: The most common location of inflammation was the anterior eye segment.
      Vogt-Koyanagi-Harada disease was the most common identifiable cause. From
      multivariate analysis, variables found to be significantly different between
      immune-related uveitis group and infectious uveitis group were age of onset,
      presence of systemic autoimmune diseases, HIV infection, and laterality.
      CONCLUSIONS: Idiopathic anterior uveitis was the most prevalent diagnosis. Vogt
      Koyanagi-Harada disease was the most common identifiable uveitis. Most immune
      related uveitis patients were young and presented with chronic bilateral
      panuveitis, with most patients in the infectious uveitis group presenting with
      chronic unilateral posterior uveitis.

PMID- 28429128
TI  - Endophthalmitis associated with Purpureocillium lilacinum during infliximab
      treatment for surgically induced necrotizing scleritis, successfully treated with
      27-gauge vitrectomy.
AB  - PURPOSE: To report a case of endophthalmitis associated with Purpureocillium
      lilacinum (P. lilacinum) during infliximab treatment for surgically induced
      necrotizing scleritis, successfully treated with 27-gauge vitrectomy. METHODS: A
      single case report. RESULTS: A 71-year-old man who had undergone
      immunosuppressive therapy, including infliximab, for surgically induced
      necrotizing scleritis (SINS) in his left eye complained of visual disturbance and
      eye pain in the eye. He had a past history of surgery for recurrent pterygium:
      pterygium excision, amnion transplantation with mitomycin C and limbal
      transplantation. Visual acuity in the left eye was counting fingers at 30 cm, and
      intraocular pressure was 3.0 mmHg. Slit-lamp examination revealed the presence of
      anterior chamber cells (3+), and a B-mode ultrasound scan showed a vitreous
      opacity. We made a diagnosis of endophthalmitis and performed 27-gauge
      microincision vitrectomy surgery (27GMIVS) with antibiotic perfusion of
      ceftazidime, vancomycin and voriconazole. Intraoperative findings included a
      fungus-like ball-shaped opacity in the vitreous, and a close-to-normal retinal
      appearance. A vitreous body culture identified the presence of P. lilacinum.
      After 2 months of antibacterial and antifungal therapy, inflammation decreased
      and visual acuity recovered to 20/100. CONCLUSIONS: This is the first report of a
      case of endophthalmitis associated with P. lilacinum during infliximab treatment
      for SINS. Scleral thinning due to necrotizing scleritis, especially during
      immunosuppressive therapy, is a risk factor for endophthalmitis. We found that
      27GMIVS was a useful strategy for such a challenging clinical situation.

PMID- 28429129
TI  - Fulminant proliferative diabetic retinopathy in the non-photocoagulated eye
      following acute renal failure.

PMID- 28429130
TI  - Long-term outcome of sacral neuromodulation for chronic refractory constipation.
AB  - PURPOSE: Sacral neuromodulation has been reported as a treatment for severe
      idiopathic constipation. This study aimed to evaluate the long-term effects of
      sacral neuromodulation by following patients who participated in a prospective,
      open-label, multicentre study up to 5 years. METHODS: Patients were followed up
      at 1, 3, 6, 12, 24, 36, 48 and 60 months. Symptoms and quality of life were
      assessed using bowel diary, the Cleveland Clinic constipation score and the Short
      Form-36 quality-of-life scale. RESULTS: Sixty-two patients (7 male, median age 40
      years) underwent test stimulation, and 45 proceeded to permanent implantation.
      Twenty-seven patients exited the study (7 withdrawn consent, 7 loss of efficacy,
      6 site-specific reasons, 4 withdrew other reasons, 2 lost to follow-up, 1 prior
      to follow-up). Eighteen patients (29%) attended 60-month follow-up. In 10
      patients who submitted bowel diary, their improvement of symptoms was sustained:
      the number of defecations per week (4.1 +/- 3.7 vs 8.1 +/- 3.4, mean +/- standard
      deviation, p < 0.001, baseline vs 60 months) and sensation of incomplete emptying
      (0.8 +/- 0.3 vs 0.2 +/- 0.1, p = 0.002). In 14 patients (23%) with Cleveland
      Clinic constipation score, improvement was sustained at 60 months [17.9 +/- 4.4
      (baseline) to 10.4 +/- 4.1, p < 0.001]. Some 103 device-related adverse events
      were reported in 27 (61%). CONCLUSION: Benefit from sacral neuromodulation in the
      long-term was observed in a small minority of patients with intractable
      constipation. The results should be interpreted with caution given the high
      dropout and complication rate during the follow-up period.

PMID- 28429131
TI  - The first comprehensive molecular detection of six honey bee viruses in Iran in
      2015-2016.
AB  - At least 18 viruses have been reported in the honey bee (Apis mellifera L.).
      However, severe diseases in honey bees are mainly caused by six viruses, and
      these are the most important in beekeeping. These viruses include: deformed wing
      virus (DWV), acute bee paralysis virus (ABPV), chronic bee paralysis virus
      (CBPV), sacbrood virus (SBV), kashmir bee virus (KBV), and black queen cell virus
      (BQCV). In this study, we evaluated 89 Iranian honey bee apiaries (during the
      period 2015-2016) suffering from symptoms of depopulation, sudden collapse,
      paralysis, or dark coloring, by employing reverse transcription-PCR. Samples were
      collected from four regions (Mazandaran, Hormozgan, Kurdistan, and Khorasan
      Razavi) of Iran. Of the 89 apiaries examined, 16 (17.97%), three (3.37%), and
      three (3.37%) were infected by DWV, ABPV, and CBPV, respectively. The study
      results for the other viruses (SBV, KBV, and BQCV) were negative. The present
      study evaluated the presence of the six most important honey bee viruses in bee
      colonies with suspected infections, and identified remarkable differences in the
      distribution patterns of the viruses in different geographic regions of Iran.

PMID- 28429132
TI  - Development of a real-time recombinase polymerase amplification assay for rapid
      and sensitive detection of porcine circovirus 2.
AB  - Porcine diseases associated with porcine circovirus 2 (PCV-2) infection have
      resulted in significant economic losses worldwide. A real-time recombinase
      polymerase amplification (RPA) assay was developed to detect PCV-2 using primers
      and an exo probe specific for the ORF2 gene. The reaction process can be
      completed in 20 min at 38  degrees C. The assay only detects PCV-2, as there was
      no cross-reaction with other pathogens important in pigs. Using the PCV-2 genomic
      DNA as template, the analytical sensitivity of the real-time RPA was 103 copies.
      The assay performance was evaluated by testing 38 field samples and compared with
      real-time PCR. The two assays demonstrated a 100% diagnostic agreement, and PCV-2
      DNA was detected in 26 samples. The R2 value of real-time RPA and real-time PCR
      was 0.954 by linear regression analysis. The real-time RPA assay provides an
      alternative tool for rapid, simple, and reliable detection of PCV-2, especially
      in remote and rural areas.

PMID- 28429133
TI  - Predominance of new G9P[8] rotaviruses closely related to Turkish strains in
      Nizhny Novgorod (Russia).
AB  - Genotype G9P[8] rotaviruses are rare in the territory of Russia. They were found
      in Nizhny Novgorod only in 2011-2012 for the first time, when their proportion
      was 25.9%. During the next two seasons, G9P[8] strains were detected in only 1.8%
      of cases. Their proportion substantially increased again in 2014, and they became
      predominant in the city by 2016. Phylogenetic analysis on the basis of gene VP7
      nucleotide sequences showed that this increase was accompanied by the emergence
      of new strains in the population. These isolates were related to Turkish strains,
      but not to Russian ones detected earlier.

PMID- 28429135
TI  - Clinical characteristics of patients with suspected cardiac chest pain and
      angiographically normal coronary arteries in a secondary care hospital.
AB  - BACKGROUND: An important number of patients with suspected cardiac chest pain
      have non-obstructive coronary artery disease. Our purpose was to describe the
      clinical characteristics of patients with normal or near-normal coronary arteries
      in routine cardiological practice in a secondary care hospital. METHODS: In 2013,
      consecutive patients referred for invasive coronary angiography with suspected
      cardiac chest pain were analysed at a single-centre (Westfriesgasthuis, Hoorn,
      the Netherlands). Coronary arteries were defined as normal or near-normal if they
      showed no stenosis or only slight wall irregularities on visual assessment.
      Patients with a final non-cardiac diagnosis for the chest pain were excluded.
      RESULTS: A total of 558 patients were included. Of these, 151 (27%) showed normal
      or near-normal coronary arteries on visual assessment. This group of patients
      were significantly more often female (p < 0.001), younger (p < 0.001) and non
      diabetic (p = 0.002). Forty percent of hospitalised patients who had normal or
      near-normal coronary arteries at coronary angiography showed an elevated
      troponin. CONCLUSION: In routine cardiological practice, around 1 out of 4
      patients with suspected cardiac chest pain undergoing invasive angiography had
      normal or near-normal coronary arteries. We suggest that premenopausal women with
      suspected cardiac chest pain could be considered for non-invasive coronary
      imaging as a first step in clinical practice.

PMID- 28429134
TI  - Systematic review of quality of life and functional outcomes in randomized
      placebo-controlled studies of medications for attention-deficit/hyperactivity
      disorder.
AB  - Children, adolescents and adults with attention-deficit/hyperactivity disorder
      (ADHD) experience functional impairment and poor health-related quality of life
      (HRQoL) in addition to symptoms of inattention/hyperactivity-impulsivity. To
      synthesize qualitatively the published evidence from randomized, double-blind,
      placebo-controlled trials of the effectiveness of pharmacotherapy on functional
      impairment or HRQoL in patients with ADHD, a systematic PubMed searching and
      screening strategy was designed to identify journal articles meeting pre
      specified criteria. Post hoc analyses and meta-analyses were excluded. HRQoL
      outcomes, functional outcomes and the principal ADHD symptom-based outcome were
      extracted from included studies. An effect size of 0.5 versus placebo was used as
      a threshold for potential clinical relevance (unreported effect sizes were
      calculated when possible). Of 291 records screened, 35 articles describing 34
      studies were included. HRQoL/functioning was usually self-rated in adults and
      proxy-rated in children/adolescents. Baseline data indicated substantial HRQoL
      deficits in children/adolescents. Placebo-adjusted effects of medication on ADHD
      symptoms, HRQoL and functioning, respectively, were statistically or nominally
      significant in 18/18, 10/12 and 7/9 studies in children/adolescents and 14/16,
      9/11 and 9/10 studies in adults. Effect sizes were >=0.5 versus placebo for
      symptoms, HRQoL and functioning, respectively, in 14/16, 7/9 and 4/8 studies in
      children/adolescents; and 6/12, 1/6 and 1/8 studies in adults. Effect sizes were
      typically larger for stimulants than for non-stimulants, for symptoms than for
      HRQoL/functioning, and for children/adolescents than for adults. The efficacy of
      ADHD medication extends beyond symptom control and may help reduce the related
      but distinct functional impairments and HRQoL deficits in patients with ADHD.

PMID- 28429136
TI  - Is there an alternative treatment for patients intolerant to antiplatelet therapy
      if percutaneous left atrial appendage closure is considered?
AB  - INTRODUCTION: Left atrial appendage (LAA) closure has become of major interest
      for patients with atrial fibrillation intolerant to oral anticoagulation therapy
      (OAC). Patients with a contraindication to both OAC and antiplatelet therapy are
      not eligible for percutaneous LAA closure. We aimed to find an alternative
      treatment for these specific patients. METHODS: From March 2014 until December
      2015 five patients were referred for percutaneous LAA closure. Alternative
      treatment was necessary due to an absolute contraindication to OAC and
      antiplatelet therapy (n = 4) or after previous failed percutaneous device
      implantation (n = 1). A stand-alone full thoracoscopic closure of the LAA using
      the Atriclip PRO device (AtriCure Inc., Dayton, OH, USA) was performed under
      guidance of transoesophageal echocardiography (TEE). After three months all
      patients underwent a computed tomography scan. Mean follow-up was 7.2 months
      [range 4.5-9.8 months]. RESULTS: All procedures were achieved without the
      occurrence of complications. Complete LAA closure was obtained in all patients
      without any residual flow confirmed by TEE. Postoperative computed tomography
      confirmed persisting adequate clip positioning with complete LAA closure and
      absence of intracardial thrombi. During follow-up no thromboembolic events
      occurred. CONCLUSION: For atrial fibrillation patients with an absolute
      contraindication to OAC and antiplatelet therapy a stand-alone, minimally
      invasive thoracoscopic closure of the LAA is a safe and feasible alternative
      treatment. This might be a solution to avoid serious bleeding complications while
      eliminating the thromboembolic risk originating from the LAA in patients who are
      not eligible for percutaneous LAA closure.

PMID- 28429137
TI  - Women's alcohol consumption and cumulative incidence of live birth following in
      vitro fertilization.
AB  - OBJECTIVE: The objective of this study was to determine the effect of alcohol
      consumption on outcomes among women undergoing in vitro fertilization (IVF).
      DESIGN: This study is a retrospective cohort study. SETTING: This study was
      performed in a private academically affiliated IVF center. PATIENTS: Patients
      included women presenting for their first IVF cycle from July 2004 through
      October 2012. INTERVENTION: Women completed self-administered questionnaires
      before their first IVF cycle, which included report of usual alcohol consumption.
      Women were categorized as non-drinkers, social drinkers, or daily drinkers, as
      well as by the number of drinks consumed per week. Competing risks analysis was
      used to calculate the cumulative incidence of live birth after 6 cycles
      stratified by alcohol consumption. MAIN OUTCOME MEASURES: Main outcome measures
      included spontaneous abortion, clinical pregnancy, and live birth following IVF.
      RESULTS: There were 591 (27.7%) non-drinkers, 1466 (68.7%) social drinkers, and
      77 (3.6%) daily drinkers (total n = 2134). In the first cycle, compared to non
      drinkers, daily drinkers had a twofold increased risk of spontaneous abortion
      (adjusted risk ratio [aRR] 2.2; 95% confidence interval [CI] 1.1-4.5) among all
      cycle starts, and while their risk of live birth was 30% lower (aRR 0.7; 95% CI
      0.4-1.3), the sample size was small, and it was not significantly lower. By the
      end of 6 cycles, social drinkers and daily drinkers did not differ from non
      drinkers in their cumulative incidence of live birth (56.1, 50.6, and 52.1%,
      respectively; both P >= 0.28). CONCLUSION: There was a trend towards lower risk
      of live birth among daily drinkers. Daily drinkers had an increased risk of
      spontaneous abortion in the first cycle, but the number of daily drinkers was
      small.

PMID- 28429138
TI  - Prothrombotic State in Asthma Is Related to Increased Levels of Inflammatory
      Cytokines, IL-6 and TNFalpha, in Peripheral Blood.
AB  - Recently, we have reported that asthma is associated with enhanced plasma
      thrombin formation and impaired fibrinolysis. The mechanisms underlying the
      prothrombotic state in this disease are unknown. Our aim was to investigate
      whether prothrombotic alterations in asthmatics are associated with inflammation.
      We studied 164 adult, white, stable asthmatics and 72 controls matched for age,
      sex, body mass index (BMI), and smoking. Plasma tumor necrosis factor alpha
      (TNFalpha), interleukin (IL)-6, and serum periostin were evaluated using ELISAs,
      and their associations with thrombin generation, fibrinolytic capacity, expressed
      as clot lysis time (CLT), and platelet markers were later analyzed. Asthma was
      characterized by 62% higher plasma IL-6 and 35% higher TNFalpha (both, p <
      0.0001). Inflammatory cytokines were higher in sporadic and persistent asthmatics
      compared to controls, also after adjustment for potential confounders. IL-6 was
      inversely related to the forced expiratory volume in 1 s/vital capacity (FEV1/VC)
      spirometry index after correction for age, sex, and BMI. IL-6 and TNFalpha were
      associated with C-reactive protein in asthmatics (beta = 0.6 [95% CI, 0.54-0.67]
      and beta = 0.33 [95% CI, 0.25-0.41], respectively) and controls (beta = 0.43 [95%
      CI, 0.29-0.57] and beta = 0.33 [95% CI, 0.18-0.48], respectively). In asthma, IL
      6 and TNFalpha positively correlated with the endogenous thrombin potential (beta
      = 0.35 [95% CI, 0.28-0.42] and beta = 0.15 [95% CI, 0.07-0.23], respectively) but
      not with CLT or platelet markers. However, TNFalpha predicted CLT in a multiple
      linear regression model. Periostin was not associated with any hemostatic
      parameters. Enhanced thrombin generation is driven in asthma by a systemic
      inflammatory state mediated by IL-6 and to a lesser extent TNFalpha, however, not
      periostin. TNFalpha might contribute to impaired fibrinolysis.

PMID- 28429139
TI  - Rates of parasitism, but not allocation of egg resources, vary among and within
      hosts of a generalist avian brood parasite.
AB  - Brown-headed cowbirds (Molothrus ater) deposit their eggs into the nests of other
      birds, which then raise the cowbird chick. Female cowbirds thus have limited
      options for impacting their offspring's development via maternal effects compared
      to most other passerines. Cowbirds can impact their offspring's phenotype by
      choosing among potential host nests, and by adjusting egg resources based on host
      characteristics. To examine whether cowbirds exhibit either or both of these
      strategies, we investigated rates of cowbird parasitism and egg investment (egg
      size, yolk-to-albumen ratio, and yolk testosterone and androstenedione) among and
      within host species in a shrubland bird community. We found that the probability
      of being parasitized by cowbirds, controlling for host status as a cowbird egg
      accepter or rejecter and ordinal date, varied significantly among host species,
      indicating an apparent preference for some hosts. Parasitism rates did not differ
      with host size, however, and despite variation in cowbird egg size among host
      species, this variation was not related to host size or cowbird preference. Among
      host species with eggs that are larger than those of the cowbird, cowbirds were
      significantly more likely to parasitize nests with relatively smaller eggs,
      whereas parasitism rates did not vary with relative egg size in host species with
      smaller eggs. There was no evidence for variation in cowbird egg components among
      or within host species. Our data indicate that cowbirds discriminate among host
      nests, but do not appear to adjust the composition of their eggs based on inter-
      or intraspecific host variation.

PMID- 28429141
TI  - Announcements for issue 5, 2017.

PMID- 28429140
TI  - A phase I/II study on stereotactic body radiotherapy with real-time tumor
      tracking using CyberKnife based on the Monte Carlo algorithm for lung tumors.
AB  - BACKGROUND: In this phase I/II study, we assessed the safety and initial efficacy
      of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor
      tracking using CyberKnife based on the Monte Carlo algorithm. METHODS: Study
      subjects had histologically confirmed primary non-small-cell lung cancer staged
      as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the
      incidence of Grade >=3 radiation pneumonitis (RP) within 180 days of the start of
      SBRT. The secondary endpoint was local control and overall survival rates. Five
      patients were initially enrolled at level 1 [50 Gy/4 fractions (Fr)]; during the
      observation period, level 0 (45 Gy/4 Fr) was opened. The dose was escalated to
      the next level when grade >=3 RP was observed in 0 out of 5 or 1 out of 10
      patients. Virtual quality assurance planning was performed for 60 Gy/4 Fr;
      however, dose constraints for the organs at risk did not appear to be within
      acceptable ranges. Therefore, level 2 (55 Gy/4 Fr) was regarded as the upper
      limit. After the recommended dose (RD) was established, 15 additional patients
      were enrolled at the RD. The prescribed dose was normalized at the 95% volume
      border of the planning target volume based on the Monte Carlo algorithm. RESULTS:
      Between September 2011 and September 2015, 40 patients (primary 30; metastasis
      10) were enrolled. Five patients were enrolled at level 0, 15 at level 1, and 20
      at level 2. Only one grade 3 RP was observed at level 1. Two-year local control
      and overall survival rates were 98 and 81%, respectively. CONCLUSION: The RD was
      55 Gy/4 Fr. SBRT with real-time tumor tracking using CyberKnife based on the
      Monte Carlo algorithm was tolerated well and appeared to be effective for
      solitary lung tumors.

PMID- 28429144
TI  - Letter to the Editor concerning "Rod fracture and lengthening intervals in
      traditional growing rods: is there a relationship?" by P. Hosseini et al. Eur
      Spine J (2016). doi:10.1007/s00586-016-4786-8.

PMID- 28429143
TI  - How to treat lumbar disc herniation in pregnancy? A systematic review on current
      standards.
AB  - PURPOSE: In this systematic review, we aim to illustrate the current and safe
      concepts in the assessment, diagnosis and management of herniated lumbar disc
      (HLD) during pregnancy. METHODS: A systematic review and reporting on the
      diagnosis, treatment and clinical results of HLD during pregnancy is performed.
      RESULTS: The MRI represents the first level and safest diagnostic tool for
      pregnant women affected by spinal problems allowing for a noninvasive and
      detailed radiological examination of the spine. The initial management of
      pregnant women affected by HLD is conservative, and primarily aimed to pain
      therapy. Whenever radicular pain and progressive neurological deficits
      unresponsive to medical management occur, surgery should be considered. Few case
      reports regarding the operative management of HLD in pregnant women have been
      published up to date. Laminectomy and/or microdiscectomy represent the classical
      and most commonly used techniques that can be safely performed without affecting
      pregnancy, delivery, or baby's health. Endoscopic discectomy may be an
      alternative. The most adequate timing and surgical position are chosen based on
      to the fetal gestational age and site of the pathology. CONCLUSIONS: Surgical
      treatments during pregnancy impose multiple medical and ethical problems. Timely
      diagnosis by MRI, careful clinical evaluation, and surgical treatment represent
      safe and effective procedures. Ongoing evolution of surgical, anesthesiological
      and obstetrical procedures results in favorable outcomes. However,
      interdisciplinary management and a wide knowledge of pregnancy-related
      pathologies are crucial for the best outcome for both mother and child.

PMID- 28429142
TI  - National Clinical Guidelines for non-surgical treatment of patients with recent
      onset low back pain or lumbar radiculopathy.
AB  - PURPOSE: To summarise recommendations about 20 non-surgical interventions for
      recent onset (<12 weeks) non-specific low back pain (LBP) and lumbar
      radiculopathy (LR) based on two guidelines from the Danish Health Authority.
      METHODS: Two multidisciplinary working groups formulated recommendations based on
      the GRADE approach. RESULTS: Sixteen recommendations were based on evidence, and
      four on consensus. Management of LBP and LR should include information about
      prognosis, warning signs, and advise to remain active. If treatment is needed,
      the guidelines suggest using patient education, different types of supervised
      exercise, and manual therapy. The guidelines recommend against acupuncture,
      routine use of imaging, targeted treatment, extraforaminal glucocorticoid
      injection, paracetamol, NSAIDs, and opioids. CONCLUSION: Recommendations are
      based on low to moderate quality evidence or on consensus, but are well aligned
      with recommendations from international guidelines. The guideline working groups
      recommend that research efforts in relation to all aspects of management of LBP
      and LR be intensified.

PMID- 28429145
TI  - Cataract and early nystagmus due to galactokinase deficiency.

PMID- 28429146
TI  - Clinical validity of biochemical and molecular analysis in diagnosing Leigh
      syndrome: a study of 106 Japanese patients.
AB  - Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and
      early childhood. It is clinically diagnosed by typical manifestations and
      characteristic computed tomography (CT) or magnetic resonance imaging (MRI)
      studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS
      is essential for deeper understanding of the disease, which may lead to the
      development of new therapies and cure. The aim of this study was to evaluate the
      clinical validity of various diagnostic tools in confirming MRC disorder in LS
      and Leigh-like syndrome (LL). The results of enzyme assays, molecular analysis,
      and cellular oxygen consumption rate (OCR) measurements were examined. Of 106
      patients, 41 were biochemically and genetically verified, and 34 had reduced MRC
      activity but no causative mutations. Seven patients with normal MRC complex
      activities had mutations in the MT-ATP6 gene. Five further patients with normal
      activity in MRC were identified with causative mutations. Conversely, 12 out of
      60 enzyme assays performed for genetically verified patients returned normal
      results. No biochemical or genetic background was confirmed for 19 patients. OCR
      was reduced in ten out of 19 patients with negative enzyme assay results.
      Inconsistent enzyme assay results between fibroblast and skeletal muscle biopsy
      samples were observed in 33% of 37 simultaneously analyzed cases. These data
      suggest that highest diagnostic rate is reached using a combined enzymatic and
      genetic approach, analyzing more than one type of biological materials where
      suitable. Microscale oxygraphy detected MRC impairment in 50% cases with no
      defect in MRC complex activities.

PMID- 28429147
TI  - Docetaxel-related fatigue in men with metastatic prostate cancer: a descriptive
      analysis.
AB  - PURPOSE: Fatigue is a prevalent and debilitating side effect of docetaxel
      chemotherapy in metastatic prostate cancer. A better understanding of the
      kinetics and nature of docetaxel-related fatigue may provide a framework for
      intervention. METHODS: This secondary analysis was performed using the MOTIF
      database, from a phase III, randomised, double-blind, placebo-controlled study of
      modafinil (200 mg/day for 15 days) for docetaxel-related fatigue in men with
      metastatic prostate cancer [1]. The pattern of fatigue was analysed using the
      MDASI (MD Anderson Symptom Inventory) score. The impact of modafinil, cumulative
      docetaxel exposure, age and smoking status on fatigue kinetics were explored.
      Fatigue-related symptoms were assessed using the SOMA6 (fatigue and related
      symptoms) subset of the SPHERE (Somatic and Psychological Health Report). Mood
      was tracked using the short form 36 health survey questionnaire (SF-36). RESULTS:
      Across four docetaxel cycles, fatigue scores were higher in the first week and
      decreased over weeks two and three. Whilst men randomised to modafinil had
      reduced fatigue scores, cumulative docetaxel had little impact. Younger men (55
      68 years) had significantly reduced fatigue scores, whereas current and ex
      smokers had higher scores. There was no significant change in mood status or
      haemoglobin across treatment cycles. Men described both 'somnolence' and 'muscle
      fatigue' contributing significantly to their symptom complex. CONCLUSIONS:
      Assessment and management of docetaxel-related fatigue remains an important
      challenge. Given the complex, multifactorial nature of fatigue, identification
      through structured interview and interventions targeted to specific 'at risk'
      groups may be the most beneficial. Understanding the temporal pattern (kinetics)
      and nature of fatigue is critical to guide this process.

PMID- 28429148
TI  - An observational time and motion study of denosumab subcutaneous injection and
      zoledronic acid intravenous infusion in patients with metastatic bone disease:
      results from three European countries.
AB  - PURPOSE: Denosumab (administered via subcutaneous injection) demonstrated
      superior efficacy versus the intravenously administered zoledronic acid in the
      prevention of skeletal-related events in an integrated analysis of three head-to
      head phase III trials in patients with bone metastases secondary to solid tumors.
      To date, no studies have evaluated treatment administration duration endpoints of
      these two agents. METHODS: A multinational, multi-site, observational time and
      motion study conducted in 10 day oncology units (DOUs) across Belgium, Germany,
      and Italy. Observations of process time included task time and active healthcare
      professional (HCP) time for pre-defined tasks. Patient time measurements included
      entering/exiting the DOU, treatment room, and treatment chair or examination
      table. RESULTS: A total of 189 patients were enrolled (82 received zoledronic
      acid and 107 received denosumab) and 238 observations were recorded (104 for
      zoledronic acid and 134 for denosumab). Mean total task time was reduced by 81%
      when denosumab was used versus zoledronic acid (8.4 versus 44.2 min; p < 0.0001;
      pooled analysis across all countries). Pooled estimates for active HCP time were
      12.2 min for zoledronic acid and 6.9 min for denosumab (44% reduction; p <
      0.0001). CONCLUSIONS: In the countries studied, using denosumab compared with
      zoledronic acid reduced total task time and active HCP time. Thus, HCPs have more
      time to dedicate to other patients or care activities. An ability to increase the
      volume of appointments within DOUs could reduce waiting lists in sites operating
      at full capacity and increase overall productivity and efficiency in hospital
      processes.

PMID- 28429149
TI  - A spiking strategy facilitates housekeeping selection for RT-qPCR analysis under
      different biotic stresses in eggplant.
AB  - Endogenous housekeeping genes are traditionally employed to normalize the
      expression of target genes in RT-qPCR studies. Assuming that a perfect
      housekeeping suitable for every condition does not exist, expression stability of
      the chosen reference gene should be evaluated at every new experiment. The
      housekeeping selection process reveals furthermore complicated and time-consuming
      when different conditions have to be compared in the same experimental dataset.
      As an alternative strategy, we spiked an external reference transcript (ERT) into
      all RNA samples of our dataset (eggplant roots subjected to different biotic
      stresses), and used it to normalize the expression levels of native candidate
      housekeeping. ERT expression resulted highly stable across all samples and
      enabled to indicate glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the most
      stable endogenous housekeeping. This result was confirmed by the use of GeNorm,
      Normfinder, and BestKeeper algorithms. This method might be generally applied to
      expedite the selection process of the best reference gene.

PMID- 28429150
TI  - Short Term High Fat Diet Induces Obesity-Enhancing Changes in Mouse Gut
      Microbiota That are Partially Reversed by Cessation of the High Fat Diet.
AB  - The gut microbiota is proposed as a "metabolic organ" involved in energy
      utilization and is associated with obesity. Dietary intervention is one of the
      approaches for obesity management. Changes in dietary components have significant
      impacts on host metabolism and gut microbiota. In the present study, we examined
      the influence of dietary fat intervention on the modification of gut mucosa
      associated microbiota profile along with body weight and metabolic parameter
      changes. Male C57BL/6J mice (6-week old) were fed a low fat diet (10% kcal fat)
      as a control or a high fat diet (HFD 60% kcal fat) for 7 weeks. In another group,
      mice were fed HFD for 5 weeks followed by low fat control diet for 2 weeks (HFD +
      Control). At 7 weeks, body weight gain, blood glucose and hepatic triacylglycerol
      levels of mice fed a HFD were significantly higher than that of the control group
      and the HFD + Control group. There were significant differences in the diversity
      and predicted functional properties of microbiota in the cecum and colon mucosa
      between the control group and the HFD group. HFD feeding reduced the ratio of
      Bacteroidetes to Firmicutes, a microbiota pattern often associated with obesity.
      The HFD + Control diet partially restored the diversity and composition of
      microbiota in the cecum to the pattern observed in mice fed a control diet. These
      results suggest that short-term high fat diet withdrawal can restore metabolic
      changes and prevent excess body weight gain, however, long-term dietary
      intervention may be required to optimize the restoration of gut microbiota in
      mouse.

PMID- 28429151
TI  - Corynebacterium species nasopharyngeal carriage in asymptomatic individuals aged
      >= 65 years in Germany.
AB  - PURPOSE: The prevalence of protective anti-diphtheria toxin antibodies decreases
      with age. Therefore, the elderly might serve as reservoir for potentially
      toxigenic Corynebacterium (C.) species (C. diphtheriae, C. ulcerans, and C.
      pseudotuberculosis). This study aimed to examine the colonization rate of the
      nasopharynx with corynebacteria of individuals aged 65 years and older. METHODS:
      In the period from October 2012 to June 2013, nasal and throat swabs were taken
      from 714 asymptomatic subjects aged 65-106 years (average age 77.2) at three
      regions in Germany and investigated for Corynebacterium species. RESULTS: A total
      of 402 strains of Corynebacterium species were isolated from 388 out of 714
      asymptomatic subjects (carriage rate 54.3%). The carriage rate was significantly
      higher in study participants living in retirement homes (68.4%) compared to those
      living autonomously at home (51.1%). Strains were isolated mostly from the nose
      (99%). Corynebacterium accolens was the most often isolated species (39.8%),
      followed by C. propinquum (24.1%), C. pseudodiphtheriticum (19.4%), and C.
      tuberculostearicum (10.2%). No C. diphtheriae, C. ulcerans, and C.
      pseudotuberculosis strains were isolated. A subsample of 74 subjects was tested
      serologically for anti-diphtheria antibodies. Protective anti-diphtheria toxin
      antibodies were found in 29.7% of the subjects; 70.3% showed no protective
      immunity. CONCLUSIONS: These results suggest that carriage of potentially
      toxigenic corynebacteria is very rare among people aged 65 and older in Germany.
      However, the low prevalence of protective anti-diphtheria toxin antibodies might
      pose a risk for acquiring diphtheria especially for the elderly.

PMID- 28429152
TI  - Effectiveness of Graded Return to Work After Multimodal Rehabilitation in
      Patients with Mental Disorders: A Propensity Score Analysis.
AB  - Purpose Graded return to work (GRTW) is a strategy aimed at bringing people
      gradually back to coping with a full workload after an extended period of sick
      leave. This study aims to determine the effect of GRTW in addition to a
      multimodal rehabilitation on longer-term work participation in people with
      chronic mental disorders (CMDs). Methods Patients filled out questionnaires at
      the start of a multimodal rehabilitation and 15 months later. Balanced groups
      (GRTW, no GRTW) were formed by propensity score matching based on 27 covariates.
      The primary outcome measures were the return to work (RTW) status at follow-up
      and the number of days on sick leave during follow-up. Results From 1062 data
      sets (GRTW 508, no GRTW 554), 381 pairs were matched (age: 47.8 years; 78%
      female; 65% affective disorders, 28% neurotic or somatic disorders). At follow
      up, 88% of the GRTW group had returned to work compared to only 73% of the
      controls (RR = 1.22, 1.13-1.31). The mean sick leave duration during the follow
      up period was 7.0 weeks in the GRTW group compared to 13.4 weeks in the control
      group (p < 0.001). Additional explorative analyses showed that these effects were
      only observed in patients with an unsure or negative subjective RTW prognosis.
      Conclusions Based on this analysis, GRTW in addition to a multimodal
      rehabilitation is effective in enhancing successful work participation in people
      with CMDs. Earlier studies showing larger effects in people with a higher risk of
      a non-RTW were confirmed.

PMID- 28429153
TI  - Relative abundance of heat shock proteins and clusterin transcripts in
      spermatozoa collected from boar routinely utilised in an artificial insemination
      centre: preliminary results.
AB  - It is widely accepted that mature sperm contains RNA. The first hypothesis was
      that sperm RNAs have no functions of their own but are simply residues of
      spermatogenesis reflecting the events that occurred during their formation in the
      testes. More recently new discoveries have essentially expanded these views,
      showing that sperm mRNAs constitute a population of stable full-length
      transcripts, many of which are selectively retained during spermatogenesis and
      delivered to oocytes contributing to early embryo development. It is well known
      that semen quality can be influenced by occasional physical stress, infection,
      and variation in temperature and the definition of new markers for evaluation of
      semen could offer knowledge about the fertility potential of a semen sample. The
      aim of the present study was to evaluate the presence and the relative quantity
      of transcripts and protein of heat shock protein 70 (HSP70), 90 (HSP90) and
      clusterin (CLU) in Percoll-selected spermatozoa collected from seven adult boars
      of proven fertility routinely employed for artificial insemination. Our results
      showed the presence of HSP70, HSP90 and CLU transcripts with different level of
      expression: high for HSPs and low for CLU transcripts. The transcript level of
      both HSPs are similar among selected spermatozoa derived from high quality sperm
      with the exception of one boar that showed a reduced content of HSP70 and HSP90
      mRNA together with a lower semen quality. At protein level, both HSPs were
      detected with similar amount among all seven boars whilst no band was evidenced
      for CLU protein.

PMID- 28429154
TI  - Developing elite Neurospora crassa strains for cellulosic ethanol production
      using fungal breeding.
AB  - The demand for renewable and sustainable energy has generated considerable
      interest in the conversion of cellulosic biomass into liquid fuels such as
      ethanol using a filamentous fungus. While attempts have been made to study
      cellulose metabolism through the use of knock-out mutants, there have been no
      systematic effort to characterize natural variation for cellulose metabolism in
      ecotypes adapted to different habitats. Here, we characterized natural variation
      in saccharification of cellulose and fermentation in 73 ecotypes and 89
      laboratory strains of the model fungus Neurospora crassa. We observed significant
      variation in both traits among natural and laboratory generated populations, with
      some elite strains performing better than the reference strain. In the F1
      population N345, 15% of the population outperformed both parents with the top
      performing strain having 10% improvement in ethanol production. These results
      suggest that natural alleles can be exploited through fungal breeding for
      developing elite industrial strains for bioethanol production.

PMID- 28429155
TI  - A letter from the Founding Editor.

PMID- 28429156
TI  - Crystallization and Preliminary X-Ray Diffraction Analysis of a Mammal Inositol
      1,3,4,5,6-Pentakisphosphate 2-Kinase.
AB  - Inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IP5 2-K) is an enzyme that
      catalyses the formation of phytic acid (IP6) from IP5 and ATP. In mammals, IP6 is
      involved in multiple events such as DNA repair and mRNA edit and it is the
      precursor of inositol pyrophosphates, emerging compounds shown to have an
      essential role in apoptosis. In addition, IP5 2-K have functions in cells
      independently of its catalytic activity, for example in rRNA biogenesis. We
      pursue the structure determination of a mammal IP5 2-K by Protein
      Crystallography. For this purpose, we have designed protocols for recombinant
      expression and purification of Mus musculus IP5 2-K (mIP5 2-K). The recombinant
      protein has been expressed in two different hosts, E. coli and insect cells using
      the LSLt and GST fusion proteins, respectively. Both macromolecule preparations
      yielded crystals of similar quality. Best crystals diffracted to 4.3 A (E. coli
      expression) and 4.0 A (insect cells expression) maximum resolution. Both type of
      crystals belong to space group P212121 with an estimated solvent content
      compatible with the presence of two molecules per asymmetric unit. Gel filtration
      experiments are in agreement with this enzyme being a monomer. Crystallographic
      data analysis is currently undergoing.

PMID- 28429157
TI  - Scenes as Micro-Cultures: Examining Heterogeneity of HIV Risk Behavior Among Gay,
      Bisexual, and Other Men Who Have Sex with Men in Toronto, Canada.
AB  - Using latent class analysis (LCA), we examined patterns of participation in
      multiple scenes, how sexual risk practices vary by scene, and psychosocial
      factors associated with these patterns among 470 gay, bisexual, and other men who
      have sex with men (GBM) recruited from Toronto. We calculated posterior
      probability of being in a class from participation in nine separate scenes. We
      used Entropy, the Bayesian information criterion and the Lo-Mendel-Rubin
      likelihood ratio test to identify the best fit model. Fit indices suggested a
      four-class solution. Half (50%) of the GBM reported no or minimal participation
      in any scene, 28% reported participating in the dance club scene, 16% reported
      participating in the BDSM, bear, and leather scenes, and 6% reported
      participating in circuit, party and play, and sex party scenes. Compared to GBM
      who did not participate in scenes, GBM participating in the BDSM-Bear-Leather
      scene were more likely to be older, white, to report higher sexual self-esteem,
      and to engage in condomless anal sex; Party and Play scene members were more
      likely to be of Asian origin, and to use drugs before and during sex, whereas
      Dance Club scene members were more likely to be younger and to report lower self
      esteem but higher hope. LCA allowed us to identify distinct social niches or
      micro-cultures and factors characterizing these micro-cultures. GBM differ in
      their risk for HIV and STIs according to characteristics associated with
      participation in distinct micro-cultures associated with scenes. Tailored
      interventions may be needed that focus on reducing HIV risk and promoting sexual
      health in specific contexts such as the BDSM-Bear-Leather and Party and Play.

PMID- 28429158
TI  - Food Insecurity, Substance Use, and Sexual Transmission Risk Behavior Among
      People Living with HIV: A Daily Level Analysis.
AB  - People living with HIV in poverty have limited tangible and mental resources
      coupled with competing demands for these resources. Competing demands require
      individuals to make choices that may be beneficial to them in the short term but
      not in the long term. Past research has shown that food insecurity is related to
      sexual risk behaviors among people living with HIV. Individuals who are food
      insecure may sell sex in order to obtain food or lack of food may lead to a
      depletion of mental resources to negotiate safe sex. Substance use may also
      create additional constraints on these already limited resources. The current
      study tested the relation between food insecurity and day-level sexual risk
      behavior and the possible mediating role that alcohol/substance use may play. Men
      and women living with HIV were enrolled in a 28-day prospective study between
      October 2012 and April 2014 in which they completed daily text message surveys
      regarding their sex behaviors and substance/alcohol use in the context of sex. A
      total of 796 participants reported sex on 3894 days. On days in which sex
      occurred, baseline food insecurity was negatively associated with daily condom
      use. There was also a significant effect of substance use in the context of sex
      on the rates of change in condom use over time, and this interaction between
      substance use and time was a partial mediator of the relation between food
      insecurity and condom use. Gender did not moderate this mediation. Situation
      specific alcohol and drug use should be integrated into interventions that target
      food insecurity and HIV prevention.

PMID- 28429159
TI  - A brief history of the discovery of the mitochondrial unfolded protein response
      in mammalian cells.
AB  - Cells have responded to stresses which cause proteins to come out of solution by
      evolving unfolded protein response mechanisms. In eukaryotic cells there are
      several such mechanisms covering the whole cell and sub-celllular organelles.
      This review describes discoveries that describe the unfolded protein response in
      the matrix compartment of mitochondria (mtUPRR) of mammalian cells.

PMID- 28429160
TI  - Neural mechanisms of risky decision making in adolescents reporting frequent
      alcohol and/or marijuana use.
AB  - Because adolescence is a period of heightened exploration of new behaviors, there
      is a natural increase in risk taking including initial use of alcohol and
      marijuana. In order to better understand potential differences in neurocognitive
      functioning among adolescents who use drugs, the current study aimed to identify
      the neural substrates of risky decision making that differ among adolescents who
      are primary users of alcohol or marijuana, primary users of both alcohol and
      marijuana, and controls who report primary use of neither drug. Participants
      completed the Balloon Analogue Risk Task (BART) while undergoing functional
      magnetic resonance imaging. Comparison of brain activation during risky decisions
      versus non-risky decisions across all subjects revealed greater response to risky
      decisions in dorsal anterior cinguate cortex (dACC), anterior insula, ventral
      striatum, and lateral prefrontal cortex. Group comparisons across non-using
      controls, primary marijuana, primary alcohol, and alcohol and marijuana users
      revealed several notable differences in the recruitment of brain regions.
      Adolescents who use both alcohol and marijauna show decreased response during
      risky decision making compared to controls in insula, striatum, and thalamus, and
      reduced differentiation of increasing risk in dACC, insula, striatum, and
      superior parietal lobe compared to controls. These results provide evidence of
      differential engagement of risky decision making circuits among adolescents with
      varying levels of alcohol and marijuana use, and may provide useful targets for
      longitudinal studies that explicitly address causality of these differences.

PMID- 28429161
TI  - On the in vivo function of the mitral heart valve leaflet: insights into tissue
      interstitial cell biomechanical coupling.
AB  - There continues to be a critical need for developing data-informed computational
      modeling techniques that enable systematic evaluations of mitral valve (MV)
      function. This is important for a better understanding of MV organ-level
      biomechanical performance, in vivo functional tissue stresses, and the
      biosynthetic responses of MV interstitial cells (MVICs) in the normal,
      pathophysiological, and surgically repaired states. In the present study, we
      utilized extant ovine MV population-averaged 3D fiducial marker data to quantify
      the MV anterior leaflet (MVAL) deformations in various kinematic states. This
      approach allowed us to make the critical connection between the in vivo
      functional and the in vitro experimental configurations. Moreover, we
      incorporated the in vivo MVAL deformations and pre-strains into an enhanced
      inverse finite element modeling framework (Path 1) to estimate the resulting in
      vivo tissue prestresses [Formula: see text] and the in vivo peak functional
      tissue stresses [Formula: see text]. These in vivo stress estimates were then
      cross-verified with the results obtained from an alternative forward modeling
      method (Path 2), by taking account of the changes in the in vitro and in vivo
      reference configurations. Moreover, by integrating the tissue-level kinematic
      results into a downscale MVIC microenvironment FE model, we were able to
      estimate, for the first time, the in vivo layer-specific MVIC deformations and
      deformation rates of the normal and surgically repaired MVALs. From these
      simulations, we determined that the placement of annuloplasty ring greatly
      reduces the peak MVIC deformation levels in a layer-specific manner. This
      suggests that the associated reductions in MVIC deformation may down-regulate MV
      extracellular matrix maintenance, ultimately leading to reduction in tissue
      mechanical integrity. These simulations provide valuable insight into MV cellular
      mechanobiology in response to organ- and tissue-level alternations induced by MV
      disease or surgical repair. They will also assist in the future development of
      computer simulation tools for guiding MV surgery procedure with enhanced
      durability and improved long-term surgical outcomes.

PMID- 28429162
TI  - Involvement of methylated HBHA expressed from Mycobacterium smegmatis in an IFN
      gamma release assay to aid discrimination between latent infection and active
      tuberculosis in BCG-vaccinated populations.
AB  - IFN-gamma release assays (IGRAs) based on region of difference 1 (RD1) antigens
      have improved diagnosis of Mycobacterium tuberculosis (M. tb) infection. However,
      IGRAs with these antigens cannot discriminate between active tuberculosis (ATB)
      and latent tuberculosis infection (LTBI). M. tb heparin-binding-hemagglutinin
      (HBHA) induces relatively high IFN-gamma responses in LTBI individuals and low
      responses in ATB patients, but purification of the native methylated HBHA from
      cultures of M. tb for immunological tests is complex and time-consuming. To
      overcome these cumbersome procedures, we constructed a recombinant Mycobacterium
      smegmatis strain that over-expressed HBHA under control of a strong furA
      promoter. The methylated activity of purified protein was verified by
      hybridization with anti-methylated Lys antibody, and the methylated HBHA (mHBHA)
      was further evaluated for antigen-specific IFN-gamma responses in BCG-vaccinated
      Chinese population. A total of 138 individuals including 86 active TB (ATB)
      patients, 15 latent TB infection (LTBI) cases, and 37 healthy controls (HC) were
      tested by using an IFN-gamma enzyme-linked immunospot (ELISPOT) assay. The
      results showed that T-cell responses against mHBHA were always lower in ATB
      patients than in LTBI individuals, regardless of the site of infection or the
      results of bacteriological tests. This allowed for a good discrimination between
      these two groups of M. tb-infected individuals, even in the BCG-vaccinated and
      high TB-incidence setting that is China. Additionally, combination of mHBHA and
      RD1 antigens in an IFN-gamma release assay enhanced diagnostic efficacy for
      active TB cases. Taken together, inclusion of the immune response to mHBHA can
      discriminate healthy LTBI cases from ATB patients.

PMID- 28429163
TI  - Antimicrobial susceptibility of bacterial isolates from patients presenting with
      ear, nose and throat (ENT) infections in the German community healthcare setting.
AB  - Empiric initial antibiotic therapy of bacterial infections is based primarily
      upon the susceptibility of the most common causative pathogens. The purpose of
      this study was to provide susceptibility data on six bacterial species known to
      cause ear, nose and throat (ENT) infections. A total of 1066 isolates collected
      during a nationwide laboratory-based surveillance study were analysed. All
      Streptococcus pyogenes isolates were penicillin (PEN)-susceptible, indicating
      that natural penicillins can still be recommended as the first-line treatment for
      group A streptococcal tonsillopharyngitis. Of the S. pneumoniae isolates, 92.9%
      were PEN-susceptible and of the Haemophilus influenzae isolates, 89.7% were
      amoxicillin-susceptible, retaining aminopenicillins as the first-line treatment
      for acute otitis media (AOM) and acute rhinosinusitis (ARS), in case antibiotic
      therapy is considered. In contrast, cefuroxime axetil seems less likely to be
      suitable for the treatment of AOM or ARS, as all Moraxella catarrhalis and >99%
      of the H. influenzae isolates were categorised as intermediate or resistant. The
      susceptibility rates of Pseudomonas aeruginosa were 97-100% for the drugs tested,
      except for the fluoroquinolones (87.6%). Overall, bacterial isolates from
      outpatients presenting with ENT infections showed low frequencies of resistance
      in Germany. However, given the emergence of multidrug resistance to standard
      antibiotics in Escherichia coli and other pathogens, inappropriate use of broad
      spectrum antibiotics for the treatment of ENT infections has to be avoided.

PMID- 28429164
TI  - Detection of gastrointestinal pathogens in oncology patients by highly
      multiplexed molecular panels.
AB  - We compared the frequency of gastrointestinal (GI) pathogen detection in an
      oncology patient population by two multiplexed molecular assays, the Luminex
      xTAG(r) Gastrointestinal Pathogen Panel (GPP, which identifies 14 GI pathogens)
      and the BioFire Gastrointestinal Panel (BFGP, which identifies 22 GI pathogens).
      We additionally reviewed the clinical characteristics of patients tested with
      both panels. A total of 200 prospectively collected and 81 archived stool samples
      were tested by both panels. In the prospective cohort, the GPP and BFGP
      identified a pathogen in 33.5% [95% confidence interval (CI): 27.3-40.35%] and
      39.6% (95% CI: 33.0%-46.6%) of samples, respectively (p = 0.25). The BFGP
      detected significantly more pathogens than the GPP (p = 0.038), with 21.3% of
      samples positive for targets only detected by the BFGP. The concordance between
      the assays was very good at 91.1% (kappa = 0.8, 95% CI: 0.7-0.9) when considering
      only pathogens detected by both assays. The most frequent pathogens detected were
      Clostridium difficile, norovirus, Campylobacter, and Salmonella species. On the
      archived samples, the BFGP was positive in 92.6% of samples but detected more
      pathogens than the GPP (86 vs. 97, p = 0.033), including both targets unique to
      the BFGP and targets common to both panels. A pathogen was more frequently
      detected in patients with hematological malignancies than solid tumors and in
      ambulatory patients compared to hospitalized patients, but these differences were
      not statistically significant. Overall, the detection rates were similar for both
      the GPP and the BFGP, and the latter detected more than one pathogen in
      additional patients. The impact of increased detection of GI pathogens by
      multiplexed panels on the clinical care of oncology patients will require further
      investigation.

PMID- 28429166
TI  - LPS administration increases CD11b+ c-Fms+ CD14+ cell population that possesses
      osteoclast differentiation potential in mice.
AB  - Osteoclasts are multinucleated giant cells that originate from a
      monocyte/macrophage lineage, and are involved in the inflammatory bone
      destruction accompanied by periodontitis. Recent studies have shown that
      osteoclast precursors reside not only in the bone marrow, but also in the
      peripheral blood and spleen, though the precise characteristics of each precursor
      have not been analyzed. We hypothesized that the number of osteoclast precursors
      in those tissues may increase under pathological conditions and contribute to
      osteoclast formation in vivo in a mouse model. To test this hypothesis, we
      attempted to identify cell populations that possess osteoclast differentiation
      potential in the bone marrow, spleen, and blood by analyzing macrophage/monocyte
      related cell surface markers such as CD11b, CD14, and colony-stimulating factor-1
      receptor (c-Fms). In the bone marrow, the CD11b- cell population, but not the
      CD11b+ cell population, differentiated into osteoclasts in the presence of
      receptor activator of nuclear factor-kappaB ligand and macrophage colony
      stimulating factor. On the other hand, in the spleen and blood, CD11b+ cells
      differentiated into osteoclasts. Interestingly, lipopolysaccharide (LPS)
      administration to the mice dramatically increased the proportion of CD11b+ c-Fms+
      CD14+ cells, which differentiated into osteoclasts, in the bone marrow and
      spleen. These results suggest that LPS administration increases the proportion of
      a distinct cell population expressing CD11b+, c-Fms+, and CD14+ in the bone
      marrow and spleen. Thus, these cell populations are considered to contribute to
      the increase in osteoclast number during inflammatory bone destruction such as
      periodontitis.

PMID- 28429165
TI  - The use of rapid test QuikRead go(r) Strep A in bacterial pharyngotonsillitis
      diagnosing and therapeutic decisions.
AB  - Group A Streptococci (GAS) are the main causative agents of bacterial
      pharyngitis, which require antibiotic therapy. Rapid diagnostic tests detecting
      GAS combined with Centor/McIsaac score enable accurate differential diagnosis
      (viral vs. bacterial) and prompt commencement of targeted treatment. The aim of
      this study was to assess the specificity, sensitivity, PPV and NPV of QuikRead
      go(r) Strep A (Orion Diagnostica Oy, Finland) recommended for the detection of
      GAS in pharyngeal swabs. Quick diagnostic test results were compared with
      physical examination findings, Centor/McIsaac score and results of reference
      testing (conventional microbial cultures). The study group of 96 participants
      consisted of 44 women (46%) and 52 men (54%); children aged 3-14 years
      constituted 46% of the patients. S. pyogenes were cultured from 43 of 96
      pharyngeal swabs. Almost half of all positive samples (47%, n = 20) were
      collected from children aged 3 to 14 years. Positive GAS cultures were confirmed
      in 33% of patients with Centor/McIsaac score of 2 points, 48% of patients with
      score of 3, and 50% of patients with score of 4-5. Microbial cultures confirmed
      the positive results of QuikRead go(r) Strep A test in 83% of cases. Test
      specificity and sensitivity were calculated for the entire study group, which
      were 85% and 91%, respectively. The PPV of the test was 83% and its NPV was 92%.
      Using quick tests to detect GAS antigens appears a good alternative to
      conventional microbial diagnosis of strep throat, as it enables making a
      diagnosis and deciding on treatment plan in one appointment.

PMID- 28429167
TI  - Corynebacterium defluvii sp. nov., isolated from Sewage.
AB  - A Gram-positive, aerobic, non-motile, rod-shapeds, catalase-positive, and oxidase
      negative strain, designated Y49T, was isolated from sewage collected from Jilin
      Agricultural University, China. It grew at 20-40 degrees C (optimum at 30 degrees
      C), at pH 6.0-8.0 (optimum at 7.0) and at 0-1.0% sodium chloride (optimum at 0%).
      The major isoprenoid quinone was menaquinone-8 (MK-8) and the polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmethylethanolamine,
      four unidentified lipids, and two unidentified aminolipids. The peptidoglycan was
      meso-diaminopimelic acid. The cell-wall sugars were galactose, arabinose, and
      glucose. The fatty acids were C9:0, C16:0, C16:1 omega9c, C17:1 omega9c, C18:3
      omega6c (6,9,12), C18:1 omega9c, and C18:0. The DNA G+C content was 51.4 mol%.
      Based on the 16S rRNA gene sequence analysis, the nearest phylogenetic neighbors
      of strain Y49T were Corynebacterium efficiens DSM 44549T (97.5%), Corynebacterium
      callunae DSM 20147T (97.2%), Corynebacterium deserti GIMN 1.010T (96.8%),
      Corynebacterium glutamicum ATCC 13032T (96.4%), and other species belonging to
      this genus (92.3-95.4%). The DNA-DNA relatedness value between strain Y49T and C.
      efficiens DSM 44549T, C. callunae DSM 20147T, C. deserti GIMN1.010T, and C.
      glutamicum ATCC 13032T was 25.5+/-2.0%, 21.1+/-1.0%, 16.5+/-0.5%, and 13.5+/
      0.9%, respectively. Based on the phylogenetic analysis, chemotaxonomic data,
      physiological characteristics and DNA-DNA hybridization data, strain Y49T
      represents a novel species of the genus Corynebacterium, for which the name
      Corynebacterium defluvii sp nov. is proposed. The type strain is Y49T (= KCTC
      39731T =CGMCC 1.15506T).

PMID- 28429168
TI  - Bedaquiline susceptibility test for totally drug-resistant tuberculosis
      Mycobacterium tuberculosis.
AB  - This study aimed to provide information that bedaquilline is significantly
      effective for treatment of totally drug resistant (TDR) Mycobacterium
      tuberculosis that shows resistant to all first- and second-line drugs-using an
      innovative disc agarose channel (DAC) system. Time-lapse images of single
      bacterial cells under culture conditions with different concentrations of
      bedaquiline were analysed by image processing software to determine minimum
      inhibitory concentrations (MICs). Bedaquiline inhibited the growth of TDR M.
      tuberculosis strains, with MIC values ranging from 0.125 to 0.5 mg/L. The results
      of the present study demonstrate that bedaquiline, newly approved by the United
      States Food and Drug Administration (FDA), may offer therapeutic solutions for
      TDR-TB.

PMID- 28429169
TI  - Nocardioides suum sp. nov. isolated from the air environment in an indoor pig
      farm.
AB  - A bacterial strain PBT33-2T was isolated from the air environment in an indoor
      pig farm. Phylogenetic analysis based on 16S rRNA gene sequences revealed that
      strain PBT33-2T belonged to the genus Nocardioides in the phylum Actinobacteria,
      and was most closely related to Nocardioides daphnia D287T in a maximum
      likelihood and neighbor-joining phylogenetic trees. Strain PBT33-2T shared 95.3%
      sequence identity with N. daphnia D287T. However, the highest sequence similarity
      was shown with N. sediminis MSL-01T (96.0%). It had less than 96.0% sequence
      identities with other type species of the genus Nocardioides. Strain PBT-33-2T
      grew at 15-45 degrees C (optimum 20-35 degrees C), pH 5.0-11.0 (optimum pH 7.0)
      and 0-4.0% (w/v) NaCl (optimum 0%). The major fatty acid and quinone were iso
      C16:0 and MK-8, and the DNA G+C content of strain PBT33-2T was 69.3 mol%. On the
      basis of poly-phasic results, strain PBT33-2T represents a novel species of the
      genus Nocardioides, for which the name Nocardioides suum sp. nov. is proposed.
      Its type strain is PBT33-2T (=KCTC 39558T =DSM 102833T).

PMID- 28429170
TI  - Comparison of energy balance between two different-sized groups of Japanese
      macaques (Macaca fuscata yakui).
AB  - Quantifying the energy balance is essential for testing socio-ecological models.
      To reveal costs and benefits of group living in Japanese macaques from the
      perspective of feeding competition, Kurihara and Hanya (Am J Primatol 77:986
      1000, 2015) previously compared feeding behavior between two different-sized
      groups of macaques (larger group 30-35 individuals; smaller group 13-15
      individuals) in the coastal forest of Yakushima, Japan. The results suggested
      that the larger group exhibited greater feeding effort because of intragroup
      scramble competition and that the smaller group suffered from higher travel
      costs, possibly owing to intergroup contest competition. However, it remained
      unclear whether the behavioral differences affected their energy budgets. The
      present study examined energetic consequences of the different feeding behaviors
      in the two groups. Using behavioral data from 10 to 13 adult females and
      nutritional composition of food items, we compared ingestion rates,
      energetic/nutritional content of diet, and energy budgets between the two groups.
      Ingestion rates and energetic/nutritional content of diet did not differ between
      the two groups. Despite the higher feeding effort of the larger group, energy
      intake did not differ between the two groups. Energy expenditure did not differ
      between the two groups because higher travel costs were negated by lower feeding
      effort in the smaller group. Consequently, the energy balance did not differ
      between the two groups. We demonstrated that the behavioral measures of feeding
      competition were not translated into their energetic condition; moreover, our
      findings re-emphasize the importance of quantifying behavioral and fitness
      measures for interpreting variation in feeding behavior properly.

PMID- 28429171
TI  - Sleeve Gastrectomy Alters Intestinal Permeability in Diet-Induced Obese Mice.
AB  - BACKGROUND: Increased lipopolysaccharide (LPS) translocation due to altered
      intestinal permeability has been suggested as a mechanism for obesity-associated
      insulin resistance. The goal of this study was to assess the effect of sleeve
      gastrectomy (SG) on intestinal barrier permeability in diet-induced obese mice.
      MATERIALS AND METHODS: Four weeks after surgery, the effects of SG on intestinal
      permeabilities were assessed ex vivo and in vivo in male C57Bl/6J mice fed a high
      fat diet. Gene expression of tight junction proteins and inflammatory cytokines
      was measured in jejunum, colon, liver, and inguinal adipose tissue. Plasma LPS
      was quantified by HPLCMS/MS spectrometry. RESULTS: SG significantly reduced body
      weight and improved glucose homeostasis, as expected. SG decreased paracellular
      (p = 0.01) and transcellular permeability (p = 0.03) in the jejunum; and
      increased mRNA levels of the tight junction proteins Jam A (p = 0.02) and
      occludin (p = 0.01). In contrast in the distal colon, paracellular permeability
      tended to be increased (p = 0.07) while transcellular permeability was
      significantly induced (p = 0.03) after SG. In vivo, the paracellular permeability
      was significantly increased 3 weeks after SG (p = 0.02). Plasma LPS level were
      increased after SG (p = 0.03), as well as mRNA levels of adipose and hepatic
      inflammatory markers (p = 0.02). CONCLUSIONS: SG significantly modifies
      intestinal permeability in a differential manner between the proximal and distal
      intestine. These changes promote LPS translocation in plasma, induce a low-grade
      pro-inflammatory state in adipose tissue and liver, but do not impair the SG
      induced glucose homeostasis improvement.

PMID- 28429172
TI  - A new species of Haematoloechus Looss, 1899 (Digenea: Plagiorchioidea:
      Haematoloechidae), a parasite of Rana psilonota Webb and R. zweifeli Hillis,
      Frost & Webb (Anura: Ranidae) in Mexico.
AB  - During an inventory of the helminths of amphibians in Mexico, specimens of an
      undescribed species of Haematoloechus Looss, 1899 (Digenea: Haematoloechidae)
      were collected from the lungs of frogs of the "tarahumarae" group in western
      Mexico. Haematoloechus longicollum n. sp. differs from other known species of
      Haematoloechus by the combination of the following characters: body elongate and
      slender in the preovarian region and broad and blunt in the postovarian region,
      ovary separated from the ventral sucker more than twice the ovary length, oral
      sucker to pharynx length ratio 1:0.56, oral sucker to ventral sucker length ratio
      1:0.80, presence of extracaecal uterine loops, absence of longitudinal
      extracaecal uterine loops, ovary and testes oval.

PMID- 28429173
TI  - A new approach to local DCO in ankle fracture dislocations: external fixation
      with diaphyseal unicortical screws applied by local anaesthesia.
AB  - PURPOSE: Ankle fracture dislocations represent a great threat for soft tissue
      viability and articular instability. The use of a temporary ankle bridging ExFix
      plays a fundamental role in the local damage control orthopaedics while waiting
      for definitive synthesis. METHODS: For this prospective research, we have
      developed a full application protocol of innovative diaphyseal monocortical
      screws fixator (Unyco-OrthofixTM) exclusively under local anaesthesia. Rigid
      selection criteria allowed us to collect nine patients during a period of almost
      2 years. VAS score was analysed for the feasibility of the procedure, and a
      thorough radiologic evaluation was performed. RESULTS: Results pointed out that
      the calcaneus pin insertion (VAS: 3.44) followed by the local anaesthetics
      injection (VAS: 3.22) was the most painful, without precluding to continue the
      procedure; fracture temporary stability was achieved in all the cases.
      CONCLUSIONS: The procedure of monocortical diaphyseal application in bridging
      external fixation is comparable to the conventional transcalcaneal traction
      maintaining the advantage in terms of speediness, independence from anaesthetists
      and feasibility within few minutes from hospital admittance even in patients
      under anticoagulants therapy, but increasing the stability of the reduction and
      improving the quality of nursing (so-called portable traction).

PMID- 28429175
TI  - Development of a Time-Resolved Fluorescence Immunoassay for the Diagnosis of
      Hepatocellular Carcinoma Based on the Detection of Glypican-3.
AB  - Glypican-3(GPC3), an oncofetal protein, is a potential novel marker for
      hepatocellular carcinoma (HCC). In this study, we attempted to establish a new
      method to detect serum GPC3 using the antibodies identified in our previous
      research, and then evaluated its clinical application for the diagnosis of HCC.
      Herein, a sandwich time-resolved fluorescence immunoassay (TRFIA) for detecting
      serum GPC3 was developed. The detection limit, analytical recovery, specificity
      and precision of the proposed TRFIA assay were satisfactory. A total of 415
      patients were collected and divided into seven groups: hepatocellular carcinoma
      (101), colorectal cancer (67), gastric cancer (44), esophageal cancer (15),
      cirrhosis (55), hepatitis (61), normal liver (72). Using this proposed method,
      the concentration of serum GPC3 in these clinical samples was detected. The
      results demonstrated that the levels of GPC3 in serum from HCC patients were
      significantly higher than that in others. Compared with the results of
      chemiluminescence immunoassay (CLIA), a high consistency (Kappa =0.84) was
      observed. Thus, an effective, sensitive and reliable TRFIA-GPC3 kit for
      diagnosing HCC was successfully developed. It offers a suitable alternative to
      existed methods of determining GPC3 and is expected to be used in clinic in the
      future.

PMID- 28429176
TI  - The log-linear response function of the bounded number-line task is unrelated to
      the psychological representation of quantity.
AB  - The bounded number-line task has been used extensively to assess the numerical
      competence of both children and adults. One consistent finding has been that
      young children display a logarithmic response function, whereas older children
      and adults display a more linear response function. Traditionally, these log
      linear functions have been interpreted as providing a transparent window onto the
      nature of the participants' psychological representations of quantity (termed
      here a direct response strategy). Here we show that the direct response strategy
      produces the log-linear response function regardless of whether the psychological
      representation of quantity is compressive or expansive. Simply put, the log
      linear response function results from task constraints rather than from the
      psychological representation of quantities. We also demonstrate that a
      proportion/subtraction response strategy produces response patterns that almost
      perfectly correlate with the psychological representation of quantity. We
      therefore urge researchers not to interpret the log-linear response pattern in
      terms of numerical representation.

PMID- 28429174
TI  - A Unique Sensitive and Highly Selective Fluorescent Naphthodiaza-Crown
      Macrocyclic Ligand Chemosensor for Hg2+ in Water.
AB  - The noticeable enhancement in fluorescence emission of O2N2-donor naphthodiaza
      crown macrocyclic ligand (L) in the presence of Hg2+ was observed in which the
      fluorescence quantum yield of free ligand L as well as L/Hg2+ complex were found
      to be as 0.29 and 0.49, respectively. The observed ultra-low limit of detection
      (LOD) for Hg2+ by L was determined as low as 1.0 * 10-11 M in water. A 1:1
      stoichiometry was also established for L/Hg2+ together with a binding constant K
      BH = 66,543 by employing fluorescence spectrophotometry. The competition
      experiments on L/Hg2+ demonstrated highly selective detection of Hg2+ in the
      presence of the library cations. A two path mechanism for detection of metal ion
      in terms of coordination of metal ion to L and/or the formation of counter ion
      was proposed by using of 1H NMR and fluorescence spectroscopy. Graphical Abstract
      pH dependence mechanism of interaction between Hg2+ and macrocyclic ligand L.

PMID- 28429177
TI  - Learning from one's own errors and those of others.
AB  - Three experiments investigated the effects of making errors oneself, as compared
      to just hearing the correct answer without error generation, hearing another
      person make an error, or being "on-the-hook," that is, possibly but not
      necessarily being the person who would be "called-on" to give a response. In all
      three experiments, generating either an error of commission or generating the
      correct response, oneself, out loud, compared to being a person who heard
      another's commission errors (or correct responses), was beneficial for later
      recall of the correct answer. Experiment 1 suggested that the decrement in recall
      from self- to other-generation could be partially offset by being "on-the-hook."
      However, this benefit was fragile and did not hold up either at a delay or when
      the presence of the other participants was downplayed. The beneficial effect of
      self-generation, both of correct responses and of errors of commission is
      consistent with reconsolidation theory. That theory holds that retrieval has a
      special status as a memory process that renders the retrieved traces labile. If
      the person was correct, reconsolidating the correct trace results in
      strengthening. If wrong, the malleability of the retrieved trace implied by
      reconsolidation theory makes it open to enhanced modification and correction. If
      the person was not the agent who retrieved, though, such as when someone else
      retrieves information, or when nothing is retrieved as is the case with omission
      errors (which we argue is truly how the term "unsuccessful retrieval" should be
      used), the benefit conferred by the special malleability entailed by the
      postulated reconsolidation process does not obtain.

PMID- 28429178
TI  - Sleep habits, fatigue, and sleepiness in Chiclayo-Peru's bus drivers.
AB  - OBJECTIVE: The objectives of the study are to describe sleep habits, fatigue, and
      sleepiness in Chiclayo's (Peru) bus drivers and explore their relation with
      traffic accidents. MATERIAL AND METHODS: This is a descriptive cross-sectional
      study with a non-probability consecutive sampling. The sample size was 126
      drivers. Sleepiness was evaluated using the Epworth Sleepiness Scale and sleep
      hygiene with validated questionnaires. We used a history of traffic accident or a
      near-traffic accident as an independent variable and applied chi-squared, t, and
      Mann-Whitney U tests to evaluate initial associations, which were later tested
      with a multivariate analysis. RESULTS: The mean age was 47.8 +/- 9, 7 years, all
      were male. Twenty-seven (21%) bus drivers drove 10 or more hours per day; twenty
      seven (21%) drove 5 or more hours without stopping; and eleven (9%) slept less
      than 6 h per day. Ninety-three (74%) drivers had fatigue while driving; thirty
      one (25%) sleepiness; thirty-six (29%) had an accident or near accident; and
      (35%) had nodding while driving. Nodding while driving (PR 2.13, IC 1.26-3.59, p
      < 0.01) and the number of years as a driver (PR 1.03, IC 1.00-1.05, p = 0.02)
      were associated with an accident or near accident. CONCLUSION: Fatigue,
      sleepiness, and a history of accident or near accident were frequent. Having had
      an accident or near accident was significantly associated with nodding while
      driving and the number of years as a driver in Chiclayo's bus drivers.

PMID- 28429179
TI  - Generalization of the Ericksen-Leslie theory.
AB  - We generalize the Ericksen-Leslie theory for the dynamics of nematic liquid
      crystals by including the director-density coupling energy [Formula: see text].
      It corresponds to the cost in energy due to the interaction of spatially varying
      mass density [Formula: see text] and the liquid crystal director [Formula: see
      text]. A striking confirmation of the theory is achieved by confronting it with
      experimental data on acoustical Freedericksz transition.

PMID- 28429180
TI  - Theoretical models for the thermo-gravitational separation process in porous
      media filled by N-component mixtures.
AB  - The aim of this work is to present a theoretical analysis of the separation of an
      N-component mixture. In this study, two analytical models explaining the thermo
      gravitational separation of components in N-component mixtures for vertical
      cavity filled by a porous medium are presented and assessed. The basic state and
      the separation are expressed in terms of the separation ratio, and the Lewis,
      cross-diffusion and Rayleigh numbers. Our computational analysis confirms that,
      for the given values of the mass fractions, thermodiffusion can be measured with
      a thermo-gravitational column, strongly supporting the experimentally determined
      transport coefficients.

PMID- 28429181
TI  - Hydrodynamic instabilities in active cholesteric liquid crystals.
AB  - We describe the basic properties and consequences of introducing active stresses,
      with principal direction along the local director, in cholesteric liquid
      crystals. The helical ground state is found to be linearly unstable to extensile
      stresses, without threshold in the limit of infinite system size, whereas
      contractile stresses are hydrodynamically screened by the cholesteric elasticity
      to give a finite threshold. This is confirmed numerically and the non-linear
      consequences of instability, in both extensile and contractile cases, are
      studied. We also consider the stresses associated to defects in the cholesteric
      pitch ([Formula: see text] lines) and show how the geometry near to the defect
      generates threshold-less flows reminiscent of those for defects in active
      nematics. At large extensile activity [Formula: see text] lines are spontaneously
      created and can form steady-state patterns sustained by constant active flows.

PMID- 28429182
TI  - Synthetic approaches toward stilbenes and their related structures.
AB  - Compounds belonging to the stilbene family have gained remarkable significance in
      pharmaceutical as well as material chemistry. The current review covers the
      various synthetic approaches for the syntheses of stilbene scaffold and related
      structures over last 30 years. In addition, this review also highlights the role
      of stilbene intermediates used in the synthesis of important molecules with
      diverse applications in the field of pharmaceutics and material science.

PMID- 28429183
TI  - Label-free okadaic acid detection using growth of gold nanoparticles in sensor
      gaps as a conductive tag.
AB  - Okadaic acid (OA) is a marine toxin ingested by shellfish. In this work, a
      simple, sensitive and label-free gap-based electrical competitive bioassay has
      been developed for this biotoxin detection. The gap-electrical biosensor is
      constructed by modifying interdigitated microelectrodes with gold nanoparticles
      (AuNPs) and using the self-catalytic growth of AuNPs as conductive bridges. In
      this development, the AuNPs growth is realized in the solution of glucose and
      chloroauric acid, with glucose oxidation used as the catalysis for growth of the
      AuNPs. The catalytic reaction product H2O2 in turn reduces chloroauric acid to
      make the AuNPs grow. The conductance signal amplification is directly determined
      by the growth efficiency of AuNPs and closely related to the catalytic activity
      of AuNPs upon their interaction with OA molecule and OA aptamer. In the absence
      of OA molecule, the OA aptamer can absorb onto the surfaces of AuNPs due to
      electrostatic interaction, and the catalytically active sites of AuNPs are fully
      blocked. Thus the AuNPs growth would not happen. In contrast, the presence of OA
      molecule can hinder the interaction of OA aptamer and AuNPs. Then the AuNPs sites
      are exposed and the catalytic growth induces the conductance signal change. The
      results demonstrated that developed biosensor was able to specifically respond to
      OA ranging from 5 ppb to 80 ppb, providing limit of detection of 1 ppb. The
      strategy is confirmed to be effective for OA detection, which indicates the label
      free OA biosensor has great potential to offer promising alternatives to the
      traditional analytical and immunological methods for OA detection.

PMID- 28429184
TI  - Interactive effects of Salicylic acid and nitric oxide in alleviating zinc
      toxicity of Safflower (Carthamus tinctorius L.).
AB  - The purpose of this study was to assess the possible protective role of exogenous
      salicylic acid (SA), sodium nitroprusside (SNP), a donor of nitric oxide, and
      their combination on 21-day-old safflower (Carthamus tinctorius L.) seedlings
      grown under zinc (Zn) stress. The results revealed that exposure to 500 uM
      ZnSO4.7H2O for 10 days markedly reduced the root and shoot dry weights in Zn
      treated plants, while the application of SA, SNP and specially SA + SNP
      significantly increased the root and shoot dry weights in seedlings subjected to
      Zn stress. Addition of SA, SNP and SA + SNP interestingly reduced root-to-shoot
      translocation of zinc and increased significantly the level of glutathione (GSH)
      and ascorbate (ASC) in leaves of Zn-stressed plants. The Zn-treated plants
      supplemented with SA and SNP revealed an improved activity of ascorbate
      glutathione cycle enzymes and those enzymes which are involved in glyoxalase
      system as compared to the plants treated with Zn only. However, no significant
      relationship was found between SA or SNP supplementation and glutathione S
      transferase activity in Zn-stressed plants. These findings demonstrate that
      exogenous application of SA or SNP could ameliorate the negative effects of Zn on
      safflower plants probably by stimulation of antioxidant defense and glyoxalase
      systems.

PMID- 28429186
TI  - What are colorectal cancer survivors' preferences for dietary advice? A best
      worst discrete choice experiment.
AB  - PURPOSE: Studies on healthy lifestyle interventions in survivors of colorectal
      cancer have been disappointing, demonstrating only modest changes. This study
      aims to quantify people's preferences for different aspects of dietary
      intervention. METHOD: A best-worst discrete choice experiment was designed and
      incorporated into a questionnaire including participants' characteristics and a
      self-assessment of lifestyle. RESULTS: The response rate was 68% and 179
      questionnaires were analysed. When analysing aggregate preferences, the modes of
      information provision selected as the most preferred were "face-to-face"
      (willingness to pay (WTP) L63.97, p <= 0.001) and "telephone" (WTP L62.36, p <
      0.001) discussions whereas group discussions were preferred least (WTP -L118.96,
      p <= 0.001). Scenarios that included hospitals were most preferred (WTP L17.94, p
      = 0.031), and the favoured provider was bowel cancer nurses (WTP L75.11, p <=
      0.001). When investigating preference heterogeneity, three sub-groups were
      identified: Firstly, "technophiles" preferring email (WTP L239.60, p <= 0.001)
      were male, were younger and had fewer risk factors. Secondly, a "one-to-one"
      group had strong preference for interventions over the telephone or at their
      local doctors and were older (WTP L642.13, p <= 0.001). Finally, a "person
      centred" group preferred face-to-face individual or group sessions (WTP L358.79,
      p < 0.001) and had a high risk lifestyle. CONCLUSION: For survivors of colorectal
      cancer, there is not one approach that suits all when it comes to providing
      dietary advice. IMPLICATIONS FOR CANCER SURVIVORS: This is important information
      to consider when planning healthy lifestyle interventions which include dietary
      advice for survivors of colorectal cancer. Aligning services to individuals'
      preferences has the potential to improve patient experience and outcomes by
      increasing uptake of healthy lifestyle advice services and promoting a more
      tailored approach to dietary modifications, acknowledging sub-groups of people
      within the total population of colorectal cancer survivors.

PMID- 28429185
TI  - High-Content Assessment of Cardiac Function Using Heart-on-a-Chip Devices as Drug
      Screening Model.
AB  - Drug discovery and development continues to be a challenge to the pharmaceutical
      industry despite great advances in cell and molecular biology that allow for the
      design of better targeted therapeutics. Many potential drug compounds fail during
      the clinical trial due to inefficacy and toxicity that were not predicted during
      preclinical stages. The fundamental problem lies with the use of traditional drug
      screening models that still largely rely on the use of cell lines or animal cell
      monolayers, which leads to lack of predictive power of human tissue and organ
      response to the drug candidates. More physiologically relevant systems are
      therefore critical in relieving the burden of high failure rates. Emerging
      knowledge and techniques in tissue engineering and microfabrication have enabled
      the development of micro-engineered systems - collectively known as organs-on
      chips - that may lead to a paradigm shift in preclinical drug screening assays.
      In this review we explore the technological advances and challenges in the
      development of heart-on-a-chip models, by addressing current assessment methods
      for drug-induced cardiotoxicity and providing a perspective on the modifications
      that should be implemented to realize the full potential of this system.

PMID- 28429187
TI  - Curcumin reverses the depressive-like behavior and insulin resistance induced by
      chronic mild stress.
AB  - Increasing evidence has demonstrated that patients with depression have a higher
      risk of developing type 2 diabetes. Insulin resistance has been identified as the
      key mechanism linking depression and diabetes. The present study established a
      rat model of depression complicated by insulin resistance using a 12-week
      exposure to chronic mild stress (CMS) and investigated the therapeutic effects of
      curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors,
      and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance
      tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters
      were detected using commercial kits. Real-time quantitative PCR was used to
      examine mRNA expression. CMS rats exhibited reduced sucrose consumption,
      increased serum glucose, insulin, triglyceride (TG), low density lipoprotein
      cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and
      corticosterone levels, as well as impaired insulin sensitivity. Curcumin
      upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein
      kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the
      metabolic abnormalities and depressive-like behaviors mentioned above. Moreover,
      curcumin increased the hepatic glycogen content by inhibiting glycogen synthase
      kinase (GSK)-3beta and prevented gluconeogenesis by inhibiting
      phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase).
      These results suggest that curcumin not only exerted antidepressant-like effects,
      but also reversed the insulin resistance and metabolic abnormalities induced by
      CMS. These data may provide evidence to support the potential use of curcumin
      against depression and/or metabolic disorders.

PMID- 28429188
TI  - 18F-Fluorodeoxyglucose uptake on positron emission tomography/computed tomography
      is associated with metastasis and epithelial-mesenchymal transition in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality
      worldwide. Several studies have investigated the relationship between 18F
      fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography and the
      prognosis of patients with HCC, although the relationship between 18F-FDG uptake
      and expression of EMT-related proteins in these patients remains unclear. We
      retrospectively enrolled 116 patients with HCC treated by curative surgical
      resection and who underwent 18F-FDG positron emission tomography/computed
      tomography (PET/CT) for preoperative staging. The relationship between the tumor
      to-liver standardized uptake value ratio (TLR) and the presence of metastasis was
      determined. By using HCC cell lines with different 18F-FDG uptake, we assessed
      the effect of 18F-FDG uptake on in vitro cell proliferation and migration on the
      inhibition of glucose uptake. Ten (29.4%) of 34 patients with high TLRs had
      extrahepatic metastases, whereas six (7.3%) of 82 patients with low TLRs had
      extrahepatic metastases (p = 0.002). Hepatocellular carcinomas with high TLRs
      showed higher expression of glucose transporter isoform 1 and EMT markers than
      did HCCs with low TLRs. After treatment with a glucose uptake inhibitor, HCC
      cells with high 18F-FDG uptake showed decreased cell proliferation and migration
      and a reversal in the expression of EMT markers. High 18F-FDG uptake on PET/CT is
      associated with frequent extrahepatic metastasis and EMT in patients with HCC.
      Inhibition of glucose uptake reduced cell proliferation, reversed EMT-related
      protein expression, and decreased cellular migration. Glycolytic regulation could
      be a new therapeutic target to reduce tumor growth and metastatic potential in
      HCCs with a high glycolytic phenotype.

PMID- 28429189
TI  - Using Time Perception to Explore Implicit Sensitivity to Emotional Stimuli in
      Autism Spectrum Disorder.
AB  - Establishing whether implicit responses to emotional cues are intact in autism
      spectrum disorder (ASD) is fundamental to ascertaining why their emotional
      understanding is compromised. We used a temporal bisection task to assess for
      responsiveness to face and wildlife images that varied in emotional salience.
      There were no significant differences between an adult ASD and comparison group,
      with both showing implicit overestimation of emotional stimuli. Further, there
      was no correlation between overestimation of emotional stimuli and autistic
      traits in undergraduate students. These data do not suggest a fundamental
      insensitivity to the arousing content of emotional images in ASD, or in
      individuals with a high degree of autistic traits. The findings have implications
      for understanding how emotional stimuli are processed in ASD.

PMID- 28429190
TI  - Study on environmental indices and heat tolerance tests in hair sheep.
AB  - The ability to predict the effects of climatic factors on animals and their
      adaptability is important for livestock production. The aim of the present study
      was to analyze whether existing indices are suitable for evaluating heat stress
      in Santa Ines and Morada Nova sheep, which are locally adapted hair sheep breeds
      from northeastern Brazil, and if the limits used to classify thermal stress are
      suitable for these breeds. Therefore, climatic, physiological, and physical
      parameters, as well as thermographic images, were collected in 26 sheep, 1 1/2
      years old, from two genetic groups (Santa Ines 12 males and 4 females; Morada
      Nov. 7 males and 3 females) for 3 days in both morning (4:00 a.m.) and afternoon
      (2:00 p.m.) with six repetitions, totalizing 156 repetitions. Statistical
      analysis included correlations and broken-line regressions. Iberia and Benezra
      indices were the tolerance tests that best correlated with the assessed
      parameters. High correlations between environmental indices and rectal or skin
      surface temperatures was observed, which indicates that these indices can be used
      for Santa Ines and Morada Nova sheep raised in central Brazil. However, some
      indicative values of thermal discomfort are different from the existing
      classification. Therefore, in order to classify appropriately, the model used
      needs to be carefully studied, because these classifying values can vary
      according to the species and model. Further research is necessary to establish
      indicators of thermal stress for sheep breeds raised in the region.

PMID- 28429191
TI  - Melanogenesis inhibition in mice using a low-fluence 1064-nm Q-switched neodymium
      doped yttrium aluminum garnet laser: a pilot study.
AB  - A low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser,
      or laser toning, has yielded favorable outcomes in various benign pigmented
      disorders. However, the exact mechanism of action of laser toning has not been
      fully elucidated. We sought to determine the inhibitory effect of laser toning on
      melanogenesis and to assess how laser passes influence the outcomes. To produce
      perceptible pigmentation, nine HRM-2 melanin-possessing hairless mice were
      treated with ultraviolet (UV) B radiation on the dorsal skin. This was followed
      by zero, two, four, or six passes of laser toning twice in 2 weeks on each
      designated quadrant. The spectrophotometric values and pigmentation-related
      protein expressions were measured. Pigment changes were found in the mice skin
      using the Fontana-Masson stain for histopathological analysis. Four- and six-pass
      laser toning significantly improved the lightness compared to that in the
      unirradiated control (p < 0.002). The Fontana-Masson stain showed that melanin
      was considerably decreased in laser-irradiated skin. As the number of laser
      passes increased, the expression of tyrosinase decreased (p < 0.008). The
      following parameters also decreased in proportion to the number of laser passes:
      MITF, TRP-1, TRP-2, p-ERK, and p-Akt. In contrast, TGF-beta increased in
      proportion to the number of laser passes. However, the changes in these six
      proteins were not statistically significant. Our study demonstrates that laser
      toning improves skin pigmentation with increased number of passes in a dose
      dependent manner. This effect is mediated by tyrosinase inhibition.

PMID- 28429192
TI  - Photoinactivation effect of eosin methylene blue and chlorophyllin sodium-copper
      against Staphylococcus aureus and Escherichia coli.
AB  - The use of eosin methylene blue according to Giemsa as photosensitizer is
      presented for the first time in this paper. The present study evaluated the
      potential application of chlorophyllin sodium copper salt (CuChlNa) and eosin
      methylene blue according to Giemsa (EMB) as antimicrobial photosensitizers (aPS)
      for photodynamic inactivation (PDI) of Staphylococcus aureus (gram-positive) and
      Escherichia coli (gram-negative) bacteria. The experiments were performed using
      S. aureus stain ATCC 25923 and E. coli ATCC 25922 in which five aPS
      concentrations (0.0, 1.0, 2.5, 5.0, 10.0, and 20.0 MUM for S. aureus and 0.0,
      5.0, 10.0, 20.0, 40.0, and 50.0 MUM for E. coli) were prepared and added in 2 mL
      of a saline solution containing the bacterial inoculum. After aPS incubation, the
      samples were divided into two groups, one kept in the dark and another submitted
      to the illumination. Then, the bacterial inactivation was determined 18 h after
      the incubation at 37  degrees C by counting the colony-forming units (CFU). The
      results revealed that both EMB and CuChlNa can be used as aPS for the
      photoinactivation of S. aureus, while only EMB was able to photoinactivate E.
      coli. Nevertheless, a more complex experimental setup was needed for
      photoinactivation of E. coli. The data showed that EMB and CuChlNa presented
      similar photoinactivation effects on S. aureus, in which bacterial growth was
      completely inhibited at photosensitizer (PS) concentrations over 5 MUM, when
      samples were previously incubated for 30 min and irradiated by a light dose of 30
      J cm-2 as a result of an illumination of 1 h at 8.3 mW cm-2 by using a red light
      at 625 nm with a 1 cm beam diameter and output power of 6.5 mW. In the case of E.
      coli, bacterial growth was completely inhibited only when combining a PS
      incubation period of 120 min with concentrations over 20 MUM.

PMID- 28429193
TI  - Effect of non-coherent infrared light (LED, lambda945 +/- 20 nm) on bone repair
      in diabetic rats-morphometric and spectral analyses.
AB  - Phototherapy using coherent light (lasers) and non-coherent light (light-emitting
      diodes (LEDs)) has been investigated for the purpose of biomodulation in
      biological tissues. Several effects can be expected, including pain moderation,
      biostimulation of cellular tropism, anti-inflammatory effects, regular
      circulatory stimulation, and tissue repair. The aim of this study was to evaluate
      the effect of LED (lambda945 +/- 20 nm, 48 mW) therapy on the regeneration
      process in femoral lesions of rats (Wistar). Seven irradiation sessions were
      held, with a 48-h interval between sessions. The animals were euthanised 14, 21,
      and 28 days after surgery. Bone samples were analysed by histomorphometry, micro
      X-ray fluorescence spectroscopy, scanning electron microscopy, and optical
      densitometry. The results demonstrated the effective positive influence of low
      intensity LED therapy using the near-infrared region on the tissue repair process
      in diabetic animals, especially in the early stages of repair (14 and 21 days
      after surgery). It can be concluded that LED therapy positively influences bone
      formation in the early stages of the bone repair process in non-diabetic and
      diabetic animals, without causing changes in the optical density and volume of
      tissue in the final stages. No influence of LED therapy was observed on the
      percentage of calcium, percentage of phosphorus, Ca/P ratio, or optical mineral
      density in non-diabetic animals. However, increased mineral concentration was
      evident in the diabetic animals treated with the LED during the repair process.

PMID- 28429194
TI  - Photobiomodulation therapy associated with treadmill training in the oxidative
      stress in a collagen-induced arthritis model.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      chronic and systemic inflammation, which leads to the destruction of the
      cartilage and bone and affects tissues in multiple joints. Oxidative stress has
      been implicated with regards to involvement in various disease conditions, such
      as diabetes mellitus and neurodegenerative, respiratory, cardiovascular, and RA
      diseases. In vivo experimental studies using photobiomodulation therapy (PBMT)
      have shown positive effects in reducing lipid peroxidation and in increasing
      antioxidant activity. The regular practice of physical exercise has also been
      reported to be a beneficial treatment capable of reducing oxidative damage. Thus,
      the aim of this study was to analyze the effects of photobiomodulation therapy at
      2- and 4-J doses associated with physical exercise on oxidative stress in an
      experimental model of RA in protein expression involving superoxide dismutase
      (SOD), glutathione peroxidase (GPX), and/or catalase (CAT) on thiobarbituric acid
      reactive substances (TBARS). In this study, 24 male Wistar rats divided into four
      groups were submitted to an RA model (i.e., collagen-induced arthritis, CIA),
      with the first immunization performed at the base of the tail on days 0 and 7
      were included. After 28 days, a third intraarticular dose was administered in
      both knees of the animals. After the last induction, PBMT was started
      immediately, transcutaneously at two points (i.e., the medial and lateral), with
      a total of 15 applications. Treadmill exercise was also started the day after the
      last induction, and lasted for 5 weeks. With respect to results, we obtained the
      decreases in the lipid peroxidation and the increases of the antioxidant
      activities of SOD, GPX and CAT, with physical exercise associated to PBMT in
      doses of 2 and 4 J. In conclusion, physical exercise associated with PBMT
      decreases lipid peroxidation and increases antioxidant activity.

PMID- 28429195
TI  - Computer-Assisted Diagnosis System for Breast Cancer in Computed Tomography Laser
      Mammography (CTLM).
AB  - Computed tomography laser mammography (Eid et al. Egyp J Radiol Nucl Med, 37(1):
      p. 633-643, 1) is a non-invasive imaging modality for breast cancer diagnosis,
      which is time-consuming and challenging for the radiologist to interpret the
      images. Some issues have increased the missed diagnosis of radiologists in visual
      manner assessment in CTLM images, such as technical reasons which are related to
      imaging quality and human error due to the structural complexity in appearance.
      The purpose of this study is to develop a computer-aided diagnosis framework to
      enhance the performance of radiologist in the interpretation of CTLM images. The
      proposed CAD system contains three main stages including segmentation of volume
      of interest (VOI), feature extraction and classification. A 3D Fuzzy segmentation
      technique has been implemented to extract the VOI. The shape and texture of
      angiogenesis in CTLM images are significant characteristics to differentiate
      malignancy or benign lesions. The 3D compactness features and 3D Grey Level Co
      occurrence matrix (GLCM) have been extracted from VOIs. Multilayer perceptron
      neural network (MLPNN) pattern recognition has developed for classification of
      the normal and abnormal lesion in CTLM images. The performance of the proposed
      CAD system has been measured with different metrics including accuracy,
      sensitivity, and specificity and area under receiver operative characteristics
      (AROC), which are 95.2, 92.4, 98.1, and 0.98%, respectively.

PMID- 28429196
TI  - Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes
      and Tumor Cells is Associated with Advanced Tumor Stage in Patients with
      Esophageal Adenocarcinoma.
AB  - BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the
      esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell
      death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells.
      Tumor cells can escape anticancer immune responses by triggering the PD1 pathway.
      Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic
      growth signals. This study aimed to evaluate the potential clinical relevance of
      PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the
      AEG. METHODS: Patients with AEG who underwent esophagectomy from 1992 to 2011
      were included in the study. Expression of PD1was evaluated by
      immunohistochemistry and correlated with long-term overall survival (OS), disease
      free survival (DFS), and various clinicopathologic parameters. RESULTS: Tumor
      biospecimens from 168 patients were analyzed. In the analysis, 81% of the
      patients showed high tumoral frequencies (>5%) of PD1-expressing TILs (TIL-PD1+),
      and 77% of patient tumors harbored high levels (>5%) of PD1+ cancer cells (cancer
      PD1+). Expression of PD1 by TILs and cancer cells correlated significantly (p <
      0.05) with patients' tumor stage and lymph node involvement. Compared with the
      patients who had low tumoral frequencies of PD1+ TILs or cancer cells, the TIL
      PD1+ and cancer-PD1+ patients demonstrated significantly reduced DFS in the
      univariate analysis (5-year DFS: 73.3 vs. 41.9%, log-rank 0.008 and 71.3 vs.
      41.6%, p = 0.008, respectively). Additionally, the cancer-PD1+ patients showed
      significantly decreased OS in the univariate analysis compared with the cancer
      PD1- patients (5-year OS: 68.8 vs. 43.5%; p = 0.047). However, these correlations
      did not reach significance in the multivariate analysis. CONCLUSIONS: The PD1
      receptor is expressed by both TILs and cancer cells in AEG. High expression of
      PD1 is associated with advanced tumor stage and lymph node involvement, but not
      with survival.

PMID- 28429197
TI  - Axillary Micrometastases and Isolated Tumor Cells Are Not an Indication for Post
      mastectomy Radiotherapy in Stage 1 and 2 Breast Cancer.
AB  - BACKGROUND: Randomized trials demonstrate equivalent locoregional control with
      sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for T1
      2 micrometastatic breast cancer, but include few mastectomy patients. Consensus
      is lacking on indications for post-mastectomy radiotherapy (PMRT) in this
      population. Herein, we evaluate locoregional recurrence (LRR) in an unselected,
      modern cohort of T1-2 breast cancer patients with micrometastases or isolated
      tumor cells (ITCs; N0i+/N1mi) having a mastectomy. METHODS: We identified
      patients with T1-2N0i+/N1mi breast cancer treated with mastectomy from January
      2006 to December 2011. Recurrent, bilateral, and neoadjuvant cases were excluded.
      The primary outcome of interest was LRR. RESULTS: Overall, 352 patients [211
      (60%) with ITCs and 141 (40%) with micrometastases] were identified. 162 (46%)
      patients had SLNB alone and one node was positive in 295 (84%) cases; 31 (9%)
      patients had PMRT and 95% had systemic therapy. At a median 6 years of follow-up,
      the overall crude LRR rate was 2.8% (n = 9), with no axillary recurrences, and
      the crude LRR rate was 3.9% among those who had SNB alone. Those with LRR had a
      median age of 55 years, median tumor size of 1.7 cm, and ductal histology; the
      majority were high-grade (89%) and estrogen receptor positive (78%), with one
      positive node (89%). There was no association between LRR and receipt of PMRT (p
      = 0.4), SLNB versus ALND (p = 0.2), or number of positive nodes (p = 0.7) using
      the log-rank test. CONCLUSIONS: LRR was infrequent among T1-2N0i+/N1mi patients
      treated with mastectomy without PMRT, with no axillary failures, suggesting that
      PMRT or nodal radiotherapy are not routinely indicated in this population.

PMID- 28429198
TI  - Managing the perioperative patient on direct oral anticoagulants.
AB  - PURPOSE: Patients are increasingly treated with direct oral anticoagulants
      (DOACs) for the prevention of stroke due to non-valvular atrial fibrillation and
      for the treatment of venous thromboembolism. When these patients present for
      urgent or emergent surgical procedures, they present a challenge to the
      anesthesiologist who must manage perioperative risk due to anticoagulation. The
      purpose of this module is to review the literature surrounding the perioperative
      management of DOACs. Timing, laboratory monitoring, and availability of reversal
      agents are important considerations to optimize patients being treated with DOACs
      who require emergent surgery. PRINCIPAL FINDINGS: Laboratory tests are not
      recommended for routine monitoring of DOACs since they do not correlate well with
      anticoagulant activity. Most widely available laboratory tests lack the
      sensitivity to detect anticoagulant effects at low plasma concentrations.
      However, a normal thrombin time for dabigatran excludes clinically significant
      drug levels. If the risk of bleeding is judged to be high because of a recent
      dose of DOAC, various options are available to mitigate bleeding. When possible,
      surgery should be delayed for at least 12 hr after the last dose of DOAC.
      Activated charcoal may mitigate the anticoagulant effect caused by DOACs if
      administered less than two hours after the drug was ingested. Four-factor
      prothrombin complex concentrates (PCCs) may be useful to reduce life-threatening
      bleeding associated with factor Xa inhibitors. Activated PCCs have been shown to
      reverse abnormal coagulation tests associated with all DOACs, but there is a lack
      of reported evidence of clinical benefit. Idarucizumab is a specific antidote
      that is effective for reversal of anticoagulation due to dabigatran. An antidote
      for rivaroxaban and apixaban (andexanet alfa) as well as a universal antidote for
      all DOACs and heparin (PER977) are in clinical development. CONCLUSION:
      Perioperative management of anticoagulation due to DOACs is a growing concern as
      the number of patients prescribed these medications increases each year. These
      patients can be safely optimized for urgent or emergent surgery by giving
      appropriate consideration to timing, monitoring, and reversal agents.

PMID- 28429199
TI  - Gastric Bypass and Influence on Improvement of NAFLD.
AB  - PURPOSE OF REVIEW: Obesity is recognized as a chronic and recurring disease,
      often accompanied by other weight-related comorbid conditions such as obstructive
      sleep apnea, hypertension, type 2 diabetes, and non-alcoholic fatty liver disease
      (NAFLD). This chapter will seek to focus on the effect of weight loss surgery
      (WLS), in particular Roux-en-Y gastric bypass (RYGB), on NAFLD. RECENT FINDINGS:
      Among several modalities available to treat NAFLD, the one most likely to achieve
      rapid, significant, and sustained improvement of liver disease is WLS. The most
      commonly studied WLS procedure at this time is RYGB, and there is significant
      evidence that this is a safe and effective procedure both for weight loss and to
      bring about improvement of multiple associated comorbid conditions, including
      NAFLD. Further research focusing on non-surgical approaches that might mimic the
      effect of WLS on liver pathology is needed.

PMID- 28429200
TI  - Achalasia: It Is Not All Black and White.
AB  - PURPOSE OF REVIEW: This review aims to shed light on subtleties of achalasia
      diagnosis, including potential pitfalls that may lead to errors. Optimal methods
      for assessment of disease severity and the relationship between achalasia and
      other motility disorders will also be reviewed with an emphasis on recent
      findings from the literature. RECENT FINDINGS: Adjunctive testing with viscous
      substances or larger water volumes should be used routinely as it improves the
      accuracy of achalasia diagnosis. Chronic opiate use can mimic achalasia. The
      timed barium swallow remains the best test for assessments of disease severity
      and prognostication, but the functional lumen-imaging probe, a newer tool which
      measures esophagogastric junction distensibility using impedance planimetry, is
      emerging as a potentially more powerful tool for these purposes. Functional
      esophagogastric junction outflow obstruction is possibly part of the achalasia
      spectrum. By addressing the potential pitfalls described, and through routine and
      standardized use of the diagnostic tools mentioned herein, the accuracy of
      diagnosis, severity assessment, and prognostication of achalasia can be improved.

PMID- 28429201
TI  - How to Approach Lymphocytic Esophagitis.
AB  - PURPOSE OF REVIEW: Lymphocytic esophagitis (LE) is an unusual esophageal
      condition defined by an increased number of lymphocytes in the esophageal
      epithelium. With few published studies of LE available, it is unclear whether LE
      is a truly distinct clinical entity or a histological manifestation of other
      known gastrointestinal disorders. This review summarizes recent studies of
      lymphocytic esophagitis. RECENT FINDINGS: Studies have suggested that LE may be
      related to eosinophilic esophagitis (EoE) or a manifestation of gastroesophageal
      reflux disease (GERD). There is an association between LE and Crohn's disease in
      children, but not in adults. Patients with LE frequently report symptoms of
      dysphagia and GERD. Treatment options for LE are limited and involve symptom
      management similar to treatment of EoE or GERD, including proton pump inhibitors
      (PPI), swallowed topical steroids, and endoscopic dilation. With no formal
      definition and a variety of clinical presentations and endoscopic findings,
      diagnosis and management of symptomatic LE patients is challenging for
      clinicians.

PMID- 28429202
TI  - Small Bowel Motility.
AB  - PURPOSE OF REVIEW: Small bowel motility disorders constitute a relatively small
      but important segment of clinical gastroenterology. Presenting features encompass
      a broad range of symptom manifestations and severity: from chronic functional
      type complaints to life-threatening nutritional impairment. Diagnostic assessment
      of patients with suspected intestinal motility disorders is often hampered by the
      complexity of measuring intestinal contractile activity in humans. In this
      review, we describe and critically comment the main current and forthcoming
      methodologies. RECENT FINDINGS: Beyond conventional small bowel manometry,
      radiological methods, and intestinal transit tests that have been available for
      several decades, now we focus on novel methodologies such as high-resolution
      manometry, magnetic resonance methodology, and endoluminal capsule image
      analysis. Gradual introduction of new approaches to diagnostic investigation of
      patients with suspected intestinal motility disorders should facilitate a less
      invasive and more accurate characterization of disturbed motor function. Enhanced
      understanding of the pathophysiological basis of clinical conditions should allow
      better application of therapeutic approaches that are also highlighted in this
      review.

PMID- 28429203
TI  - Regulating the New: A Consideration of CRISPR and Approaches to Professional
      Standards of Practitioners of Chinese Medicine in Australia and Accessing the
      NDIS.

PMID- 28429204
TI  - Gastroduodenal stenting: is still useful in the treatment of malignant
      obstruction?

PMID- 28429205
TI  - Comparison of digital tomosynthesis and computed tomography for lung nodule
      detection in SOS screening program.
AB  - PURPOSE: To compare the lung nodules' detection of digital tomosynthesis (DTS)
      and computed tomography (CT) in the context of the SOS (Studio OSservazionale)
      prospective screening program for lung cancer detection. MATERIALS AND METHODS:
      One hundred and thirty-two of the 1843 subjects enrolled in the SOS study
      underwent CT because non-calcified nodules with diameters larger than 5 mm and/or
      multiple nodules were present in DTS. Two expert radiologists reviewed the exams
      classifying the nodules based on their radiological appearance and their
      dimension. LUNG-RADS classification was applied to compare receiver operator
      characteristics curve between CT and DTS with respect to final diagnosis. CT was
      used as gold standard. RESULTS: DTS and CT detected 208 and 179 nodules in the
      132 subjects, respectively. Of these 208 nodules, 189 (91%) were solid, partially
      solid, and ground glass opacity. CT confirmed 140/189 (74%) of these nodules but
      found 4 nodules that were not detected by DTS. DTS and CT were concordant in 62%
      of the cases applying the 5-point LUNG-RADS scale. The concordance rose to 86% on
      a suspicious/non-suspicious binary scale. The areas under the curve in receiver
      operator characteristics were 0.89 (95% CI 0.83-0.94) and 0.80 (95% CI 0.72-0.89)
      for CT and DTS, respectively. The mean effective dose was 0.09 +/- 0.04 mSv for
      DTS and 4.90 +/- 1.20 mSv for CT. CONCLUSIONS: The use of a common classification
      for nodule detection in DTS and CT helps in comparing the two technologies. DTS
      detected and correctly classified 74% of the nodules seen by CT but lost 4
      nodules identified by CT. Concordance between DTS and CT rose to 86% of the
      nodules when considering LUNG-RADS on a binary scale.

PMID- 28429206
TI  - Stent insertion for malignant superior vena cava syndrome: effectiveness and long
      term outcome.
AB  - PURPOSE: To determine the clinical effectiveness and long-term outcome of stent
      insertion for malignant superior vena cava (SVC) syndrome. MATERIALS AND METHODS:
      From June 2010 to April 2016, 47 patients with malignant SVC syndrome were
      treated with stent insertion in our center. Data regarding the technical success,
      clinical success, and long-term outcome were collected and analyzed
      retrospectively. RESULTS: SVC stent insertion was successfully performed in all
      patients. A total of 65 stents were used. No procedure-related complication
      occurred in these patients. The mean SVC pressure gradient decreased from 17.8
      mmHg before stent insertion to 7.6 mmHg after stent insertion (P < 0.001).
      Clinical success was 100%. During a mean follow-up period of 6 months (range 10
      days-13 months), 25 patients underwent subsequent anti-cancer treatment. Six
      patients (12.8%) experienced re-obstruction of stent 1 to 189 days (median 76
      days) after stent insertion. All patients died during the follow-up. The median
      stent patency time and survival were 339 and 167 days, respectively. The
      cumulative 3-, 6-, and 12-month stent patency rates were 93.4, 87.4, and 81.2%,
      respectively. The cumulative 3-, 6-, and 12-month survival rates were 83, 38.3,
      and 2.1%, respectively. The independent predictors of prolonging survival after
      stent insertion were lower tumor stage (P = 0.018) and subsequent anti-cancer
      treatment after stent insertion (P = 0.009). CONCLUSION: Stent insertion is a
      simple, safe, and effective method for patients with malignant SVC syndrome.
      Subsequent anti-cancer treatment after stent insertion may increase the survival.

PMID- 28429207
TI  - Organizational and welfare mode of breast centers network: a survey of Sicilian
      radiologists.
AB  - The European Society of Breast Cancer Specialists has created quality indicators
      for breast units to establish the minimum standards of care for patients. In
      Italy, each region differs, indeed, in terms of health care and services
      warranted to patients suffering from breast cancer. Since Sicilian Regional
      Administration today is still disregarding implementation of the provisions
      contained in the proposal of the Ministry of Health entitled "Guidelines on
      Organizational and Health Care Methods of Breast Centers Network" in November
      2015 the Sicilian Regional Group of the Italian Society of Radiology (SIRM)
      decided to carry out a survey to see the position of the Sicilian Healthcare
      System and define the gap to bridge over. Sicilian breast imaging radiologists
      were asked to fill in a questionnaire concerning the type of job relationship
      (public or private sector), qualification (Manager, Department Manager,
      Freelancer) and years of experience on breast imaging. With regard to
      technological requirements, were answered the questions about the number, type,
      age and completeness of accessories of the equipment supplied in the Sicilian
      healthcare facilities. The data showed that over 64% of breast imagers in
      Sicilian centers work in breast units, whereas only 18% are involved in screening
      programs. A majority of radiologists (81%) working in the breast health care
      system is very experienced (more than 10 years of experience in the field). The
      result provided concerning the medical and technical staff demonstrates an uneven
      situation, but overall an inadequate value compared with the required guidelines
      especially in interventional procedures. The aim of this paper is to illustrate
      the method used and the results obtained. These data have to be shared with
      policy makers to enhance quality improvement in Sicilian Breast Center Network.

PMID- 28429208
TI  - Ultra-low-dose periradicular infiltration of the lumbar spine: spot scanning and
      its potential for further dose reduction by replacing helical planning CT.
AB  - PURPOSE: Computed tomography (CT)-guided periradicular infiltration has become an
      accepted procedure for treating radiculopathy-associated low back pain. The
      purpose of this study is to compare spot scanning and segmental helical planning
      CT in terms of dose reduction. MATERIALS AND METHODS: Eighty-five patients
      underwent CT-guided single-site lumbar periradicular therapy. Prior imaging was
      not available for planning. Sixty-three patients were examined with a new
      dedicated spot scanning technique (group I), and twenty-two patients underwent
      conventional segmental planning CT examinations with helical image acquisition
      serving as controls (group II). Examinations were reviewed retrospectively for
      dose-length product (DLP) and number of acquisitions required for intervention.
      Pain reduction accomplished with the intervention was recorded for quality
      assurance. RESULTS: Median DLP was 0.80 mGy cm for spot scanning versus 6.50 mGy
      cm for segmental planning CT. Thus, the contribution of the planning scan to the
      total interventional dose decreased from 73 to 25%. As a result, the total
      interventional dose was reduced significantly from a median DLP of 8.90 mGy cm to
      3.20 mGy cm (-64%). Acquisitions required during the intervention had a median
      DLP of 2.40 mGy cm for group I and 2.35 mGy cm for group II, showing no
      significant difference. Median pain reduction in both groups was two points on
      the numeric rating scale. CONCLUSION: Dedicated spot scanning for planning
      reduced the total median effective dose of the intervention by more than 64%
      without increasing the number of images required during the interventional
      procedure. Significant pain reduction was achieved with both approaches. Spot
      scanning is recommended for dose reduction.

PMID- 28429209
TI  - Analysis of Gut Microbiota in Patients with Parkinson's Disease.
AB  - Gut microbiota of patients with Parkinson's disease and healthy volunteers was
      analyzed by the method of high throughput 16S rRNA sequencing of bacterial
      genomes. In patients with Parkinson's diseases, changes in the content of 9
      genera and 15 species of microorganisms were revealed: reduced content of Dorea,
      Bacteroides, Prevotella, Faecalibacterium, Bacteroides massiliensis, Stoquefichus
      massiliensis, Bacteroides coprocola, Blautia glucerasea, Dorea longicatena,
      Bacteroides dorei, Bacteroides plebeus, Prevotella copri, Coprococcus eutactus,
      and Ruminococcus callidus, and increased content of Christensenella, Catabacter,
      Lactobacillus, Oscillospira, Bifidobacterium, Christensenella minuta, Catabacter
      hongkongensis, Lactobacillus mucosae, Ruminococcus bromii, and Papillibacter
      cinnamivorans. This microbiological pattern of gut microflora can trigger local
      inflammation followed by aggregation of alpha-synuclein and generation of Lewy
      bodies.

PMID- 28429210
TI  - Prenatal Hyperhomocysteinemia Impairs Hypothalamic Regulation of Reproductive
      Cycles in Rat Progeny.
AB  - Effects of prenatal hyperhomocysteinemia on hypothalamic regulation of estrous
      cycles were studied in female rats. In mature rats exposed to prenatal
      hyperhomocysteinemia, changes in the catecholamine content in hypothalamic areas
      responsible for the formation of the preovulatory surge of gonadotropin-releasing
      hormone were revealed: the level of norepinephrine in the medial preoptic area
      decreased and concentration of dopamine in the median eminence with arcuate
      nuclei increased. Administration of melatonin attenuated the observed changes,
      which can be related to neuroprotective effects of this hormone determined by its
      antioxidant properties.

PMID- 28429211
TI  - Influence of Humic Acids Extracted from Peat by Different Methods on Functional
      Activity of Macrophages in Vitro.
AB  - We studied activation of macrophages with humic acids extracted from peat of
      large deposits in the Tomsk region by two extraction methods: by hydroxide or
      sodium pyrophosphate. Humic acid of lowland peat types containing large amounts
      of aromatic carbon, phenolic and alcohol groups, carbohydrate residues and
      ethers, irrespectively of the extraction methods contained LPS admixture that
      probably determines their activating properties. Humic acid of upland peat types
      characterized by high content of carbonyl, carboxyl, and ester groups enhance NO
      production and reduce arginase expression, but these effects were minimized when
      sodium hydroxide was used as an extraction solvent. Pyrophosphate samples of the
      upland peat types were characterized by aromaticity and diversity of functional
      groups and have a significant advantage because of they induce specific endotoxin
      independent stimulating action on antigen presenting cells.

PMID- 28429212
TI  - Experimental Study of a Radiopharmaceutical Agent Based on Modified Fatty Acid
      Labeled with Technetium-99m.
AB  - Using rat model of coronary occlusion, we studied pharmacokinetics and the
      efficiency of a new radiopharmaceutical agent 99mTc-PDA-DTPA intended for
      diagnostics of changes in myocardial metabolism and its analogue 123I-PMPDA.
      99mTc-PDA-DTPA was eliminated mostly by the kidneys and maximal concentration in
      the heart was attained within 60 min after intravenous injection; no accumulation
      in the area of myocardial infarction was observed. The studied substance was
      inferior to its analogue 123I-PMPDA by the quality of scintigraphic visualization
      of the heart.

PMID- 28429213
TI  - Effect of Compound Sbt-828, a New Indole Derivative Exhibiting Antiaggregant
      Activity, on the Prostacyclin-Thromboxane A2 Balance.
AB  - We investigated the effect of a new indole derivative Sbt-828 with antiaggregant
      properties on prostacyclin-generating activity of the vascular wall and
      thromboxane A2 level in platelets of intact rats. The substance under study did
      not affect prostacyclin production by the vascular wall and significantly reduced
      thromboxane A2 level, being superior to the reference drug acetylsalicylic acid
      by 1.6 times, as seen from reduced malonic dialdehyde level in the thrombin
      induced rat platelets.

PMID- 28429214
TI  - Analysis of Synergistic Effects of Antimicrobial Peptide Arenicin-1 and
      Conventional Antibiotics.
AB  - We studied combined effects of antimicrobial peptide arenicin-1 from lugworm
      Arenicola marina and some conventional antibiotics. A number of drug combinations
      with pronounced synergistic effects were revealed. The influence of antibacterial
      activity assessment conditions was determined and the methodology excluding false
      positive test results was developed.

PMID- 28429215
TI  - Effect of Preparation Based on Trametes Pubescens Xylotroph Fungi on Lipid
      Peroxidation in the Blood of Experimental Animals under Conditions of Dark
      Stress.
AB  - Using the model of dark stress caused by animal maintenance at dimmed light we
      showed that Trametin (product obtained during liquid-phase culturing of Trametes
      pubescens xylotroph fungi) effectively prevented oxidative stress under
      conditions of light deprivation. The preparation increased the level of
      unsaturation of lipids, reduced the concentration of primary and end-products of
      LPO, and increases both the integral parameter of the antioxidant defense system
      (total antioxidant activity) and its components (activity of superoxide dismutase
      and reduced glutathione).

PMID- 28429216
TI  - Effect of N- and C-Terminal Modifications on Cytotoxic Properties of
      Antimicrobial Peptide Tachyplesin I.
AB  - We analyze the effects of N-terminal acetylation and C-terminal amidation on the
      cytotoxic properties of beta-hairpin antimicrobial peptide tachyplesin I. MTT
      assay showed that modified tachyplesin I exhibited increased cytotoxicity toward
      both tumor and normal human cells. Hemolytic activity of modified tachyplesin I
      was also higher than that of the initial molecule. In contrast to non-modified
      tachyplesin I, the peptide with C- and N-terminal modifications is resistant to
      proteolytic degradation in fresh human serum. C- and N-terminal modifications
      make tachyplesin I more attractive prototype of anticancer drug due to its more
      potent cytotoxic effect and better pharmacokinetic properties.

PMID- 28429217
TI  - Adrenoceptors in Dopaminergic Regulation of Rat Myocardial Contractility in Rats
      During Ontogeny.
AB  - The effects of different dopamine concentrations on contractility of myocardium
      with blocked alpha- or beta-adrenoceptors were examined in vitro in 21- and 100
      day old rats. In myocardial strips with blocked alpha-adrenoceptors, dopamine (10
      5 M) increased the right atrial contractile force. By contrast, this
      neurotransmitter (10-9-10-5 M) reduced the contractile force of atrial and
      ventricular strips with blocked beta-adrenoceptors.

PMID- 28429218
TI  - Modification of Calcium-Activated Chloride Currents in Cerebellar Purkinje
      Neurons.
AB  - The whole-cell voltage clamp technique was employed to record the total ionic
      currents in rat cerebellar Purkinje neurons. When intrapipette solution contained
      120 mM KCl, replacement of the standard external physiological saline with Na
      free solution resulted in appearance of inward tail current after the end of the
      depolarizing pulse. When intrapipette potassium ions were replaced for cesium
      ones, the tail currents were observed even in the presence of normal Na+
      concentration (140 mM) in the external solution. Tail currents were not observed
      when external solution contained no Cl- and/or Ca2+ ions. Niflumic acid (25-100
      MUM) blocked these currents by 80-100%. Complete replacement of external Na+ for
      Tris ions pronouncedly augmented the amplitude and duration of the tail currents.
      These findings suggest that the tail transients in rat cerebellar Purkinje
      neurons are calcium-activated chloride currents whose amplitude and kinetics
      depend on ionic composition of the extracellular and intracellular solutions.

PMID- 28429219
TI  - Effects of Different Modes of Hypobaric Hypoxia on the Content of Epigenetic
      Factors in the Rat in Neurons of Rat Neocortex.
AB  - We studied the effects of different modes of hypobaric hypoxia on the content of
      epigenetic factors acH3K24, meH3K9, and meDNA modulating conformational
      characteristics of chromatin and gene expression in neurons of associative
      complex of rat parietal neocortex. Severe destructive hypoxia dramatically
      reduced the level of acH3K24 in 3 h after the end of exposure and increased
      meH3K9 and meDNA content. By contrast, 3-fold (but not single) adaptive exposure
      to moderate hypobaric hypoxia that produced a neuroprotective effect enhanced
      neuronal acH3K24 expression and decreased both meH3K9 and meDNA levels. Elevated
      acH3K24 content facilitates, while increased content of meH3K9 hampers binding of
      transcription factors to the target genes. At the same time, increased expression
      of meDNA suppresses transcription. The role of modification of epigenetic
      mechanisms in the regulation of proadaptive genes under the effects of hypoxic
      exposure according to various protocols is discussed.

PMID- 28429220
TI  - Antithrombin Activity of Erythrocyte Microvesicles.
AB  - Coagulation and optical (based on chromogenic substrate) methods were employed to
      examine antithrombin activity of erythrocytes and erythrocyte-derived
      microvesicles isolated days 7, 14, 21, and 28 on erythrocyte storage. The
      erythrocyte-derived microvesicles decelerated fibrin clot formation from
      fibrinogen in the presence of exogenous thrombin both with and without heparin.
      Microvesicles reduced optical density of chromogenic substrate. These data
      suggest that erythrocyte-derived microvesicles display a prominent antithrombin
      activity, which significantly increases during erythrocyte storage.

PMID- 28429221
TI  - Associations of Osteocalcin, Osteoprotegerin, and Calcitonin with Inflammation
      Biomarkers in Atherosclerotic Plaques of Coronary Arteries.
AB  - We studied associations of osteocalcin, osteoprotegerin, and calcitonin with
      markers of inflammation in atherosclerotic plaques in coronary arteries and
      assessed the influence of these biomolecules on calcification of atherosclerotic
      plaques. The initial stage of calcification of atherosclerotic plaques is
      characterized by activation of inflammatory processes, which is seen from
      increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-alpha, and IL
      1beta). Progressive calcification of atherosclerotic plaques is accompanied by
      insignificant accumulation of calcitonin and osteoprotegerin. The exception is
      osteocalcin, its concentration significantly increased during calcification. The
      results suggest that severe vascular calcification can be regarded as non
      specific marker of atherosclerosis. Instability of atherosclerotic plaques is
      associated with higher level of calcification.

PMID- 28429222
TI  - Comparison of the Effects of Mitochondria-Targeted Antioxidant 10-(6'
      Plastoquinonyl)Decyltriphenylphosphonium Bromide (SkQ1) and a Fragment of its
      Molecule Dodecyltriphenylphosphonium on Carrageenan-Induced Acute Inflammation in
      Mouse Model of Subcuteneous Air Pouch.
AB  - The effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)
      decyltriphenylphosphonium bromide (SkQ1) and its fragment
      dodecyltriphenylphosphonium (C12TPP), weak uncouplers of respiration and
      oxidative phosphorylation, was studied using a mouse model of carrageenan-induced
      acute inflammation in the subcutaneous air pouch. In our model, SkQ1 demonstrated
      a strong anti-inflammatory effect that manifested in a decrease in the absolute
      number of inflammatory cells, mainly neutrophils, and their relative number in
      parallel with an increase in macrophages and mast cell content in the
      inflammatory exudate. The concentration of proinflammatory cytokine IL-6 in the
      exudate also tended to decrease. C12TPP produced no significant effect on the
      inflammation process.

PMID- 28429223
TI  - Sex-Related Characteristics of Systemic Hormonal Homeostasis in Rats with Sarcoma
      C-45 Cells Transplanted to the Lung.
AB  - Sex-related systemic status of pituitary and thyroid hormones and cortisol was
      studied in rats on days 7 and 14 after transplantation of sarcoma C-45 cells into
      the lung. Females demonstrated slower development of the tumor process (49.0+/
      10.7 vs. 32.0+/-3.9 days in males). Injection of tumor cells causes similar
      disorders in the levels of ACTH, thyrotropic hormone, and prolactin in males and
      females and opposite disorders in the thyroid and glucocorticoid homeostasis
      associated in males (in contrast to females) with reduction of cortisol level (by
      1.9 times) and increase in the concentrations of total thyroxine forms (by 1.4
      times) and triiodothyronine (by 2.9 times) by day 14. Early sex-related shifts in
      the status of hormone that are a component of the adaptive system attest to their
      possible relationship with different course of the malignant process in male and
      female rats.

PMID- 28429224
TI  - Combined Effects of M1 Muscarinic Acetylcholine Receptor Agonist TBPB and alpha7n
      Acetylcholine Receptor Activator GTS-21 on Mouse Mortality and Blood
      Concentration of Proinflammatory Cytokines in Sepsis.
AB  - Experiments on random-bred albino mice showed that M1 muscarinic acetylcholine
      receptor agonist (TBPB) and alpha7n-acetylcholine receptor agonist (GTS-21)
      significantly reduced mortality of mice with experimental sepsis
      (intraperitoneally administration of E. coli) in 4 and 24 h after modeling by
      reducing blood concentration of proinflammatory cytokines TNF-alpha, IL-1beta,
      and IL-6. Combined treatment with TBPB and GTS-21 determined their additive
      effect.

PMID- 28429225
TI  - Design of Chemical Conjugate for Targeted Therapy of Multiple Sclerosis Based of
      Constant Fragment of Human Antibody Heavy Chain and Peptoid Analog of Autoantigen
      MOG35-55.
AB  - Elimination of B cells producing autoantibodies to neuroantigens is considered as
      beneficial in the treatment of multiple sclerosis. Myelin oligodendrocyte
      glycoprotein (MOG) is a significant autoantigen in multiple sclerosis. It was
      shown that MOG-like peptoid AMogP3 can bind autoantibodies produced by
      pathological lymphocytes. We propose a structure of an innovative drug for
      targeted elimination of the pool of autoreactive B cells responsible for multiple
      sclerosis pathogenesis; this compound is a complex of peptoid AMogP3 with Fc
      fragment of human immunoglobulin. The obtained Fc-PEG-AMogP3 conjugate
      effectively interact with autoreactive antibodies, which attests to their high
      therapeutic potential.

PMID- 28429226
TI  - Screening of Some Dioxaboreninopyridine and Aniline Derivatives for Carcinogenic
      Properties Using a Model Cell-Free System of Regenerating Rat Liver.
AB  - We studied the effects of some aniline and dioxaborininopyridine derivatives on
      the rate of oxidative deamination of putrescine and polyamines in a tissue with
      high mitotic index. These effects were evaluated quantitatively by measuring
      diamine oxidase and polyamine oxidase activities in a model cell-free test system
      of regenerating rat liver tissue. Aniline derivatives exhibited mainly
      antiproliferative effects and promoted oxidative degradation of putrescine,
      spermidine, and spermine. Dioxaborininopyridine derivatives inhibited this
      process, thus exhibiting carcinogenic properties.

PMID- 28429227
TI  - Secretion of Thioredoxin Peroxidase Protein of Cat Liver Fluke Opisthorchis
      felineus during Modeling of Experimental Opisthorchiasis.
AB  - Mechanisms of thioredoxin peroxidase secretion by Opisthorchis felineus were
      studied in vivo and in vitro. Specific antibodies were obtained and used for
      western blotting and immunohistochemical detection in Syrian hamster model of
      opisthorchiasis. Secreted thioredoxin peroxidase protein was accumulated in the
      worm incubation medium under conditions of oxidative stress and in bile duct
      cells of hamsters with chronic opisthorchiasis.

PMID- 28429228
TI  - Magnetic Resonance Imaging of Tumors with the Use of Iron Oxide Magnetic
      Nanoparticles as a Contrast Agent.
AB  - We studied the possibility of using BSA-coated magnetic iron oxide nanoparticles
      for magnetic resonance imaging diagnosis of C6 glioblastoma, 4T1 mammary
      adenocarcinoma, and RS-1 hepatic mucous carcinoma. In all three cases, magnetic
      nanoparticles accumulated in the tumor and its large vessels. Magnetic resonance
      imaging with contrast agent allows visualization of the tumor tissue and its
      vascularization.

PMID- 28429229
TI  - Microcirculatory Bed, Microcirculation, and Smoking-Associated Endothelial
      Dysfunction in Young Adults.
AB  - Computer-assisted video biomicroscopy of bulbar conjunctiva was employed to
      examine the sequelae of endothelial dysfunction manifested by microcirculatory
      bed abnormalities and microcirculation disturbances. The signs of endothelial
      dysfunction provoked by tobacco smoking in young adults disappeared after
      cessation of smoking, which resulted in pronounced widening of arterioles and
      capillaries as well as moderation of intravascular erythrocyte aggregation.

PMID- 28429230
TI  - Influence of Implants Surface Properties on Bone Tissue Formation in the Ectopic
      Osteogenesis Test.
AB  - We studied the influence of the characteristics of oxide porous coatings on
      osteogenesis and integration of new bone tissue and titanium implant surface in
      the ectopic osteogenesis test. Implants with coating with pore size 2-20 MU
      exhibit better osteogenic and osteoconductive characteristics than implants with
      homogenous surface and smooth relief (pore size 0.5-5.0 MU). Physical
      characteristics of the surface of the material along with chemical composition of
      the coating are essential for the formation of bone tissue and its integration
      with the implant.

PMID- 28429231
TI  - A Method for Microencapsulation of Cells and a Device for Its Realization.
AB  - The device for cell encapsulation makes it possible to fabricate microcapsules of
      a preset size with even smooth surface, without defects or adhesion to each
      other, with viable cells inside the capsule. The cells were derived from newborn
      piglet pancreases.

PMID- 28429232
TI  - Detection of Potential Metastatic Prostate Cancer Circulating Biomarkers by
      Comparison of miRNA Profiles in DU145 Cells and Culture Medium.
AB  - We studied the profile of miRNA secreted into culture medium by DU145 prostate
      cancer cells and identified a subset of miRNAs characterized by the absence of
      correlation of their content in the cell and medium, which is likely a result of
      specific secretion. Three of these miRNA, hsa-miR-4417, hsa-miR-3175, and hsa-miR
      6782-5p, exhibit the highest expression and are candidate circulating biomarkers
      for metastatic activity of prostate cancer. Two of these miRNA are coded by
      introns of genes linked with genome stability maintenance and chromatin
      remodeling regulation.

PMID- 28429233
TI  - Role of Methylation in the Regulation of Apoptosis Genes APAF1, DAPK1, and BCL2
      in Breast Cancer.
AB  - Changes in the levels of expression of proapoptotic genes APAF1 and DAPK1 and
      antiapoptotic gene BCL2 were studied by real time PCR in specimens of tumors and
      histologically intact tissue from 28 patients with breast cancer. The expression
      of APAF1 and DAPK1 was below the normal in the majority of tumor samples
      (p<0.05), while the level of BCL2 mRNA more often surpassed the normal (p<0.1).
      Study of the same sample of specimens by methylspecific PCR showed predominance
      of APAF1 and DAPK1 hypermethylation (p<0.05 and p<0.1, respectively) and more
      frequent hypomethylation of BCL2. A significant correlation between changes in
      the levels of expression and methylation (r=0.40-0.49; p<0.05) was detected for
      all three genes (APAF1, DAPK1, and BCL2). The results suggest that methylation
      play an important role in the regulation of these apoptosis system genes in
      breast cancer.

PMID- 28429234
TI  - Neuron-to-Neuron Transfer of FUS in Drosophila Primary Neuronal Culture Is
      Enhanced by ALS-Associated Mutations.
AB  - The DNA- and RNA-binding protein fused in sarcoma (FUS) has been pathologically
      and genetically linked to amyotrophic lateral sclerosis (ALS) or frontotemporal
      lobar degeneration (FTLD). Cytoplasmic FUS-positive inclusions were identified in
      the brain and spinal cord of a subset of patients suffering with ALS/FTLD. An
      increasing number of reports suggest that FUS protein can behave in a prion-like
      manner. However, no neuropathological studies or experimental data were available
      regarding cell-to-cell spread of these pathological protein assemblies. In the
      present report, we investigated the ability of wild-type and mutant forms of FUS
      to transfer between neuronal cells. We combined the use of Drosophila models for
      FUS proteinopathies with that of the primary neuronal cultures to address neuron
      to-neuron transfer of FUS proteins. Using conditional co-culture models and an
      optimized flow cytometry-based methodology, we demonstrated that ALS-mutant forms
      of FUS proteins can transfer between well-differentiated mature Drosophila
      neurons. These new observations support that a propagating mechanism could be
      applicable to FUS, leading to the sequential dissemination of pathological
      proteins over years.

PMID- 28429235
TI  - Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier
      Functions by Memantine.
AB  - Vascular risk factors have been linked to cognitive decline and dementia in the
      elderly. Microvascular inflammation, especially of the endothelium, may
      contribute to the progression of neurodegenerative events in Alzheimer's disease
      (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor
      antagonist, is a licensed drug used for the treatment of moderate to severe AD.
      However, little information is available regarding its anti-inflammatory effects
      on the endothelium. In this study, we investigated the effects of memantine on
      human brain microvascular endothelial dysfunction induced by the pro-inflammatory
      cytokine tumor necrosis factor-alpha (TNF-alpha). Our results show that memantine
      prevents the attachment of monocyte THP-1 cells to human brain microvascular
      endothelial cells (HBMVEs). An in vitro BBB model experiment displayed that
      memantine could rescue TNF-alpha-induced disruption of the in vitro BBB model. In
      addition, memantine also interferes with monocyte transmigration across the BBB
      model. Our results indicate that TNF-alpha significantly increased the expression
      of cell adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, which was
      prevented by pretreatment with memantine. Mechanistically, memantine reversed
      activation of the transcription factor NF-kappaB by preventing the
      phosphorylation and degradation of its inhibitor IkappaBalpha. Our data is the
      first to describe a novel anti-inflammatory mechanism driven by the endothelial
      cell-mediated neuroprotective effects of memantine.

PMID- 28429236
TI  - The course of headache in patients with moderate-to-severe headache due to mild
      traumatic brain injury: a retrospective cross-sectional study.
AB  - BACKGROUND: Little is known about the long-term course of headache in patients
      with moderate-to-severe headache due to traumatic brain injury  (TBI). We
      evaluated the course of headache in patients with moderate-to-severe headache due
      to mild TBI. METHODS: Since September 2009, patients with TBI prospectively rated
      their headache using a numeric rating scale (NRS). From the database containing
      935 patients with TBI between September 2009 and December 2013, 259 patients were
      included according to following criteria: (1) newly onset moderate-to-severe
      headache (NRS >= 4) due to head trauma; (2) age >= 15 years; (3) Glasgow Coma
      Scale >= 13; (4) transient loss of consciousness <= 30 min; and (5) radiographic
      evaluation, such as computed tomography or magnetic resonance image. We evaluated
      initial and follow-up NRS scores to determine the significance of NRS changes and
      identified risk factors for moderate-to-severe headache at 36-month follow-up.
      RESULTS: At 36-month follow-up, 225 patients (86.9%) reported improved headache
      (NRS <= 3) while 34 (13.1%) reported no improvement. The NRS scores were
      significantly decreased within a month (P < 0.001). The follow-up NRS scores at
      12-, 24-, and 36-months were lower than those at one month (P < 0.001). Multiple
      logistic regression analysis showed that post-traumatic seizure (odds ratio,
      2.162; 95% CI, 1.095-6.542; P = 0.041) and traumatic intracranial hemorrhage
      (odds ratio, 2.854; 95% CI, 1.241-10.372; P = 0.024) were independent risk
      factors for moderate-to-severe headache at 36-month follow-up. CONCLUSIONS: The
      course of headache in patients with mild TBI continuously improved until 36-month
      follow-up. However, 13.1% of patients still suffered from moderate-to-severe
      headache at 36-month follow-up, for whom post-traumatic seizure and traumatic
      intracranial hemorrhage might be risk factors.

PMID- 28429237
TI  - Atypical and anaplastic meningioma: outcomes in a population based study.
AB  - Atypical and anaplastic meningiomas (AAM) are aggressive tumors. This study is
      aimed at examining associations between patient and tumor-related factors and
      tumor-related death in patients with AAM. We conducted a population-based cohort
      study utilizing prospectively collected data from the Surveillance, Epidemiology,
      and End Results (SEER) database. Patients with diagnosis of AAM from 1973 to 2012
      in the SEER database were included. Patients lacking clinical information were
      excluded. Multivariate analysis between patient and lesion characteristics, and
      AAM-related death was performed to adjust for confounding factors. We identified
      and included 522 patients in our study. Mean age at diagnosis was 60.8 +/- 15.7
      years. The majority of patients were White(73%), 15.5% Black, and 9.8% Asian.
      Average tumor size was 48.2 +/- 20.3 mm. The tumor was locally confined in 57.1%,
      whereas it had intracranial extension in 29.3%, and extracranial extension in
      8.8% of patients. The vast majority (94.8%) of tumors were supratentorial. Gross
      total resection (GTR) was documented in 65.5% of patients. Age at diagnosis (p =
      0.001), tumor size (p = 0.003), surgery result (GTR vs. subtotal resection, p =
      0.027), and radiation therapy (p = 0.2) were found to be significantly different
      between the comparison groups. In a multivariate proportional competing risk
      regression analysis age (HR 1.03, CI [1.01,1.04], p < 0.001), infratentorial
      location (HR 2.81, CI [1.20, 6.56], p = 0.017), tumor size (HR 1.01, CI
      [1.00,1.02], p = 0.032),and radiation treatment (HR 1.52, CI [1.11, 2.09], p =
      0.01) were significantly associated with tumor-related death. The association of
      age at diagnosis, tumor size, location, and radiotherapy with overall survival in
      patients with AAM is demonstrated. The results provide a context for
      individualized treatment plans in patients with AAM. Additional studies focusing
      on issues such as the use of radiation and chemotherapy will clarify the best
      modality to achieve disease control.

PMID- 28429238
TI  - The growing role of biology in the treatment of glioblastoma: no more one kind of
      disease.

PMID- 28429239
TI  - Development and initial validation of a short three-dimensional inventory of
      character strengths.
AB  - PURPOSE: Character strength is described as a positive and organized pattern of
      emotions, thoughts, and behaviors. It serves as a schema that organizes
      categories of information toward the self, others, and the world, and provides
      the self-aware knowledge that facilitates the pursuit of goals, values, and
      ethical principles. Recent research has suggested that three reliable factors
      emerge from the measures of character strengths: caring, inquisitiveness, and
      self-control. The goal of this paper is to develop a psychometrically sound short
      measure of character strength. METHODS: The questions were addressed in two
      studies using two independent samples: a cross-cultural (i.e., 518 Asians and 556
      Westerners) sample, and a cross-population (i.e., 175 community participants and
      171 inpatients) sample in China. RESULTS: Findings from the exploratory and
      confirmatory factor analysis suggested a cross-cultural three-factor model of
      character strength that could be measured by the Three-dimensional Inventory of
      Character Strengths (TICS). A multigroup confirmatory factor analysis further
      indicated that the number of factors and factor loadings was invariant in the
      medical and community samples. This result indicated that the brief inventory
      could be applied to a medical context. Internal reliability, content validity,
      and predictive validity were good, although the predictive validity of the three
      character strengths for psychological symptoms in the medical sample was more
      modest than that in the community sample. CONCLUSIONS: TICS is expected to be
      used for screening populations at risk, and a tool to aid mental health
      professionals in group-based treatment/intervention planning. It also should be
      noted that this short inventory should be used with caution for individual
      decision making.

PMID- 28429240
TI  - Clinical setting-based smoking cessation programme and the quality of life in
      people living with HIV in Austria and Germany.
AB  - PURPOSE: To report on the global quality of life (QOL) in people living with HIV
      (PLWHIV) and how a smoking cessation intervention influences the changes in QOL.
      METHODS: Participants were asked to fill out a questionnaire during visits to
      their HIV outpatient clinic consisting of sociodemographic information, general
      health data and the WHOQOL HIV-Bref. Exhaled carbon monoxide measurements were
      used to confirm the smoking status, based on which participants classified as
      smokers received a short 5 min structured intervention and were offered
      participation in a full smoking cessation programme consisting of five sessions.
      Follow-up was done 8 months after the baseline. RESULTS: Overall 447 (mean age =
      45.5) participants took part with 221 being classified as smokers. A total of 165
      (74.6%) participants received a short intervention and 63 (29.4%) agreed to
      participate in the full program. At baseline, differences in QoL were observed,
      where smokers had lower QoL in domains of physical (M = 16.1 vs. 15.3, p = 0.009)
      and psychological (M = 15.3 vs. 14.6, p = 0.021) well-being, independency level
      (M = 16.1 vs. 15.2, p = 0.003) and environment (M = 16.5 vs. 16.0, p = 0.036). At
      study end, 27 (12.2%) participants quit smoking; 12 (19.0%) participants of the
      full programme and 15 (14.7%) that received the short intervention. There were no
      significant differences in QoL between those that continued to smoke and quitters
      at follow-up. CONCLUSION: Quality of life results may be used to better
      understand the underlying motivation of PLWHIV who start cessation programs. In
      order to reduce the high prevalence and health burden that smoking causes in
      PLWHIV, it is necessary to introduce effective interventions that can be used in
      the clinical settings.

PMID- 28429242
TI  - Genetics of Dyslipidemia and Ischemic Heart Disease.
AB  - PURPOSE OF REVIEW: Genetic dyslipidemias contribute to the prevalence of ischemic
      heart disease. The field of genetic dyslipidemias and their influence on
      atherosclerotic heart disease is rapidly developing and accumulating increasing
      evidence. The purpose of this review is to describe the current state of
      knowledge in regard to inherited atherogenic dyslipidemias. The disorders of
      familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed.
      Genetic technology has made rapid advancements, leading to new discoveries in
      inherited atherogenic dyslipidemias, which will be explored in this review, as
      well as a description of possible future developments. Increasing attention has
      come upon the genetic disorders of familial hypercholesterolemia and elevated
      lipoprotein(a). RECENT FINDINGS: This review includes new knowledge of these
      disorders including description of these disorders, their method of diagnosis,
      their prevalence, their genetic underpinnings, and their effect on the
      development of cardiovascular disease. In addition, it discusses major advances
      in genetic technology, including the completion of the human genome sequence,
      next-generation sequencing, and genome-wide association studies. Also discussed
      are rare variant studies with specific genetic mechanisms involved in inherited
      dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9
      (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease
      is rapidly growing, which will result in a bright future of novel mechanisms of
      action and new therapeutics.

PMID- 28429241
TI  - Pharmacological Approaches to the Management of Secondary Progressive Multiple
      Sclerosis.
AB  - It is well recognised that the majority of the impact of multiple sclerosis (MS),
      both personal and societal, arises in the progressive phase where disability
      accumulates inexorably. As such, progressive MS (PMS) has been the target of
      pharmacological therapies for many years. However, there are no current licensed
      treatments for PMS. This stands in marked contrast to relapsing remitting MS
      (RRMS) where trials have resulted in numerous licensed therapies. PMS has proven
      to be a more difficult challenge compared to RRMS and this review focuses on
      secondary progressive MS (SPMS), where relapses occur before the onset of
      gradual, irreversible disability, and not primary progressive MS where disability
      accumulation occurs without prior relapses. Although there are similarities
      between the two forms, in both cases pinpointing when PMS starts is difficult in
      a condition in which disability can vary from day to day. There is also an
      overlap between the pathology of relapsing and progressive MS and this has
      contributed to the lack of well-defined outcomes, both surrogates and clinically
      relevant outcomes in PMS. In this review, we used the search term 'randomised
      controlled clinical drug trials in secondary progressive MS' in publications
      since 1988 together with recently completed trials where results were available.
      We found 34 trials involving 21 different molecules, of which 38% were successful
      in reaching their primary outcome. In general, the trials were well designed
      (e.g. double blind) with sample sizes ranging from 35 to 1949 subjects. The
      majority were parallel group, but there were also multi-arm and multidose trials
      as well as the more recent use of adaptive designs. The disability outcome most
      commonly used was the Expanded Disability Status Scale (EDSS) in all phases, but
      also magnetic resonance imaging (MRI)-measured brain atrophy has been utilised as
      a surrogate endpoint in phase II studies. The majority of the treatments tested
      in SPMS over the years were initially successful in RRMS. This has a number of
      implications in terms of targeting SPMS, but principally implies that the optimal
      strategy to target SPMS is to utilise the prodrome of relapses to initiate a
      therapy that will aim to both prevent progression and slow its accumulation. This
      approach is in agreement with the early targeting of MS but requires treatments
      that are both effective and safe if it is to be used before disability is a major
      problem. Recent successes will hopefully result in the first licensed therapy for
      PMS and enable us to test this approach.

PMID- 28429243
TI  - SLCO1B1 polymorphisms and plasma estrone conjugates in postmenopausal women with
      ER+ breast cancer: genome-wide association studies of the estrone pathway.
AB  - BACKGROUND: Estrone (E1), the major circulating estrogen in postmenopausal women,
      promotes estrogen-receptor positive (ER+) breast tumor growth and proliferation.
      Two major reactions contribute to E1 plasma concentrations, aromatase (CYP19A1)
      catalyzed E1 synthesis from androstenedione and steroid sulfatase (STS) catalyzed
      hydrolysis of estrone conjugates (E1Cs). E1Cs have been associated with breast
      cancer risk and may contribute to tumor progression since STS is expressed in
      breast cancer where its activity exceeds that of aromatase. METHODS: We performed
      genome-wide association studies (GWAS) to identify SNPs associated with variation
      in plasma concentrations of E1Cs, E1, and androstenedione in 774 postmenopausal
      women with resected early-stage ER+ breast cancer. Hormone concentrations were
      measured prior to aromatase inhibitor therapy. RESULTS: Multiple SNPs in SLCO1B1,
      a gene encoding a hepatic influx transporter, displayed genome-wide significant
      associations with E1C plasma concentrations and with the E1C/E1 ratio. The top
      SNP for E1C concentrations, rs4149056 (p = 3.74E-11), was a missense variant that
      results in reduced transporter activity. Patients homozygous for the variant
      allele had significantly higher average E1C plasma concentrations than did other
      patients. Furthermore, three other SLCO1B1 SNPs, not in LD with rs4149056, were
      associated with both E1C concentrations and the E1C/E1 ratio and were cis-eQTLs
      for SLCO1B3. GWAS signals of suggestive significance were also observed for E1,
      androstenedione, and the E1/androstenedione ratio. CONCLUSION: These results
      suggest a mechanism for genetic variation in E1C plasma concentrations as well as
      possible SNP biomarkers to identify ER+ breast cancer patients for whom STS
      inhibitors might be of clinical value.

PMID- 28429244
TI  - Fluctuating asymmetry of meristic traits: an isofemale line analysis in an
      invasive drosophilid, Zaprionus indianus.
AB  - Metric (e.g., body size) and meristic (e.g., bristle number) traits are of
      general use in quantitative genetic studies, and the phenotypic variance is
      subdivided into a genetic and a non-genetic environmental component. The non
      genetic variance may have two origins: a common garden effect between individuals
      and a developmental instability within the same individual. Developmental
      instability may be studied by considering the fluctuating asymmetry (FA) between
      the two sides of the body. The isofemale line technique is a convenient method
      for investigating the architecture of natural populations but has been rarely
      implemented for investigating FA. In this paper, we use this experimental design
      for analyzing four meristic traits in eight populations of the cosmopolitan
      Zaprionus indianus. A study of the correlation between left and right side of
      each line revealed that almost 90% of the variability was due to a developmental
      noise, while a much higher correlation among the means of the lines from the same
      population was observed. A slight trend toward a directional asymmetry was
      observed: more thoracic bristles on the left side. Four kinds of indices, scaled
      or non-scaled to the mean were used for comparing the different traits. Unscaled
      values (mean absolute values or standard deviation of each line) revealed a
      linear increase with the means. Interestingly the results of ovariole number were
      included in the same regression. With the scaled indices (mean absolute divided
      by each individual value or stadard deviation devided by the mean), the
      differences among traits were considerably decreased, but still remained
      significant. The mean FA of the various traits were not correlated, suggesting
      that each trait harbors its own developmental stability. The CVs of FA were high
      with a magnitude similar to those of the trait themselves, slightly less than
      10%. Finally, even with the isofemale line design, which is a powerful means for
      unravelling slight genetic variations, we did not to find any clear indication of
      a genetic component of FA under the optimal environmental conditions used in this
      study.

PMID- 28429245
TI  - Assessing Pruritus in Hidradenitis Suppurativa: A Cross-Sectional Study.
AB  - BACKGROUND: Pruritus is still a forgotten aspect of hidradenitis suppurativa (HS)
      and, to date, has never been adequately studied. OBJECTIVE: The aim of this study
      was to determine the prevalence, and explore the characteristics, of pruritus in
      a well-defined cohort of HS patients. SETTING: An academic hospital-based cross
      sectional study in The Netherlands. METHODS: A numerical rating scale (NRS, 0-10)
      was used to determine the prevalence of HS-related itch (NRS score >=3).
      Candidate predictors for pruritus were subsequently determined using logistic
      regression models, and the impact of pruritus was assessed using a modified five
      dimensional (5-D) itch scale. Associated serological and histological markers of
      pruritus were (semi-)quantitatively investigated in a subpopulation. RESULTS: The
      prevalence rate of pruritus in 211 HS patients was 57.3%, with a mean NRS score
      of 6.1 +/- 2.0. Patients with a pruritus NRS score >=3 had more HS-affected body
      sites than patients with a score <3 (p < 0.001). The occurrence of a pruritus NRS
      score >=3 was associated with Hurley III disease (odds ratio [OR] 7.73; p =
      0.003) and pain (OR 1.34; p < 0.001). Pruritus affected sleep and activities of
      daily living (ADL) in the majority of cases, with an associated modified 5-D itch
      score of 13.7 +/- 3.6 (on a scale from 5 to 25) in 52 HS patients. Histological
      examination showed eosinophilic granulocytes were present in 25% (2/8) of the
      perilesional skin and 63% (10/16) of the lesional skin, while a perineural
      infiltrate was found in 25% (2/8) and 69% (11/16) of the perilesional and
      lesional skin, respectively. CONCLUSION: Pruritus is a frequent but underreported
      symptom in patients with HS. Its moderate to severe intensity and significant
      impact on daily activities have great potential to impair patients' quality of
      life.

PMID- 28429246
TI  - Comparison of Efficacy and Safety of Caspofungin Versus Micafungin in Pediatric
      Allogeneic Stem Cell Transplant Recipients: A Retrospective Analysis.
AB  - INTRODUCTION: The high morbidity and mortality associated with invasive fungal
      infections (IFIs) provide the rationale for antifungal prophylaxis in immuno
      compromised pediatric patients undergoing hematopoietic stem cell transplantation
      (HSCT). Caspofungin and micafungin are antifungal agents of interest for
      prophylaxis of IFIs because of their potency against Candida and minimal toxicity
      or interactions with other drugs. Few studies have demonstrated the safety and
      efficacy of such echinocandins as prophylaxis for IFIs in patients undergoing
      HSCT. METHODS: This retrospective cohort study compared caspofungin and
      micafungin for prevention of IFIs in 93 pediatric patients undergoing HSCT for
      oncological or non-oncological disease. The observation began with the first dose
      of antifungal agent and ended 3 months after transplantation. RESULTS: Patients
      in the micafungin group had a higher overall treatment success rate of 87.2
      versus 84.8% in the caspofungin group, but the difference was not significant.
      There were no statistically significant differences in the incidence or type of
      proven/probable IFIs between the 2 groups. The low incidence of death did not
      differ statistically between the groups. Patients in the caspofungin group
      presented more frequently with fever, during and after neutropenia. In both
      groups, we observed an expected worsening of blood chemistry parameters. There
      were no adverse events definitely attributable to the two antifungal agents.
      CONCLUSION: These results demonstrate good efficacy and tolerability for
      caspofungin and micafungin. However, better results with respect to the incidence
      and resolution of fever in the micafungin group may suggest its use in preference
      to that of caspofungin.

PMID- 28429248
TI  - Time in therapeutic range as a marker for thrombotic and bleeding outcomes in
      Fontan patients.
AB  - Fontan patients managed with warfarin are at risk not only for thrombotic events,
      but also for bleeding episodes as a consequence of anticoagulation treatment. The
      aim of this study was to determine whether time spent in patient specified
      therapeutic range (TTR), when managed in a cardiology-based pharmacist managed
      anticoagulation clinic (PMAC), is a useful target metric for monitoring, as well
      as improving outcomes. A single center retrospective review was conducted
      evaluating TTR of all Fontan patients (n = 45) on warfarin managed in our
      outpatient cardiology pharmacist managed anticoagulation clinic (PMAC) during a
      19 month time frame. The primary outcome was time spent within, above, and below
      therapeutic range. Secondary outcomes were thrombotic event (TE) incidence pre-
      and post PMAC enrollment and bleeding event incidence during PMAC management. Of
      the Fontan patients included, 55.6% were male and the median age at latest
      anticoagulation clinic follow-up was 19 years (IQR 13, 29). A composite 52.9
      patient years of warfarin therapy was evaluated during the study time frame. The
      mean TTR for patients was 84.1 +/- 5.2%. The most frequent reasons for non
      therapeutic INRs were diet changes (42.8%), medication non-compliance (13.7%),
      and drug interactions (8.8%). Only one TE occurred during the study time frame.
      The incidence of TE in this population was decreased after PMAC enrollment (1 per
      52.9 patient year versus 1 event per 17.4 patient year; p < 0.0002). Two major
      bleeds that required emergency department visit occurred during this time, none
      were cerebral or gastrointestinal. In Fontan patients anticoagulated with
      warfarin, a greater than 80% TTR can be achieved in a PMAC. Such high time in
      therapeutic range was associated with excellent outcomes, despite the obvious
      complexity of this population.

PMID- 28429247
TI  - A Review of the Novel Application and Potential Adverse Effects of Proton Pump
      Inhibitors.
AB  - Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that
      target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely
      used in the treatment of gastric acid-related diseases including peptic ulcer
      disease, erosive esophagitis and gastroesophageal reflux disease, and so on.
      These drugs present an excellent safety profile and have become one of the most
      commonly prescribed drugs in primary and specialty care. Except for gastric acid
      related diseases, PPIs can also be used in the treatment of Helicobacter pylori
      infection, viral infections, respiratory system diseases, cancer and so on.
      Although PPIs are mainly used short term in patients with peptic ulcer disease,
      nowadays these drugs are increasingly used long term, and frequently for a
      lifetime, for instance in patients with typical or atypical symptoms of
      gastroesophageal reflux disease and in NSAID or aspirin users at risk of
      gastrotoxicity and related complications including hemorrhage, perforation and
      gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse
      effects, such as osteoporotic fracture, renal damage, infection (pneumonia and
      clostridium difficile infection), rhabdomyolysis, nutritional deficiencies
      (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article,
      we will review some novel uses of PPIs in other fields and summarize the
      underlying adverse reactions.

PMID- 28429249
TI  - Are there moral differences between maternal spindle transfer and pronuclear
      transfer?
AB  - This paper examines whether there are moral differences between the mitochondrial
      replacement techniques that have been recently developed in order to help women
      afflicted by mitochondrial DNA diseases to have genetically related children
      absent such conditions: maternal spindle transfer (MST) and pronuclear transfer
      (PNT). Firstly, it examines whether there is a moral difference between MST and
      PNT in terms of the divide between somatic interventions and germline
      interventions. Secondly, it considers whether PNT and MST are morally distinct
      under a therapy/creation optic. Finally, it investigates whether there is a moral
      difference between MST and PNT from a human embryo destruction point of view. I
      conclude, contra recent arguments, that regarding the first two points there is
      no moral differences between PNT and MST; and that regarding the third one MST is
      morally preferable to PNT, but only if we hold a gradualist account of the moral
      value of human embryos where zygotes have slight moral value.

PMID- 28429250
TI  - Exploring geospatial techniques for spatiotemporal change detection in land cover
      dynamics along Soan River, Pakistan.
AB  - Classification of land cover dynamics via satellite imagery has played
      indispensible services in developing effective management strategies for
      evaluation and management of water resources. The present study employed
      geospatial techniques, i.e., integrated GIS and remote sensing for effectual land
      change study. Hybrid classification approach was applied using ERDAS Imagine 11
      to detect changes in land cover dynamics using satellite imagery of Landsat 4, 5
      TM, Landsat 7 ETM, and Landsat 8 OLI for the years of 1992, 2002, and 2015,
      respectively. The study area was classified into four categories, i.e.,
      vegetation, water body, barren, and urban area. Resultant maps, overlay maps, and
      post classification comparison maps were produced using ArcGIS 10.2 indicated
      remarkable shrinkage of water body up to 58.81%, reduction in vegetation area
      53.24%, and increase in urban and barren area to 49.04 and 137.32%, respectively.
      The significant changes in land cover dynamics of Soan River are posing threats
      to its survival. Therefore, proper management, policies, and development of land
      use inventory are needs of the hour for saving Soan River.

PMID- 28429251
TI  - Air-water CO2 and CH4 fluxes along a river-reservoir continuum: Case study in the
      Pengxi River, a tributary of the Yangtze River in the Three Gorges Reservoir,
      China.
AB  - Water surface greenhouse gas (GHG) emissions in freshwater reservoirs are closely
      related to limnological processes in the water column. Affected by both reservoir
      operation and seasonal changes, variations in the hydro-morphological conditions
      in the river-reservoir continuum will create distinctive patterns in water
      surface GHG emissions. A one-year field survey was carried out in the Pengxi
      River-reservoir continuum, a part of the Three Gorges Reservoir (TGR) immediately
      after the TGR reached its maximum water level. The annual average water surface
      CO2 and CH4 emissions at the riverine background sampling sites were 6.23 +/-
      0.93 and 0.025 +/- 0.006 mmol h-1 m-2, respectively. The CO2 emissions were
      higher than those in the downstream reservoirs. The development of phytoplankton
      controlled the downstream decrease in water surface CO2 emissions. The presence
      of thermal stratification in the permanent backwater area supported extensive
      phytoplankton blooms, resulting in a carbon sink during several months of the
      year. The CH4 emissions were mainly impacted by water temperature and dissolved
      organic carbon. The greatest water surface CH4 emission was detected in the
      fluctuating backwater area, likely due to a shallower water column and abundant
      organic matter. The Pengxi River backwater area did not show significant increase
      in water surface GHG emissions reported in tropical reservoirs. In evaluating the
      net GHG emissions by the impoundment of TGR, the net change in the carbon budget
      and the contribution of nitrogen and phosphorus should be taken into
      consideration in this eutrophic river-reservoir continuum.

PMID- 28429252
TI  - Analysis of global gene expression profiles during the flowering initiation
      process of Lilium * formolongi.
AB  - The onset of flowering is critical for the reproductive development of plants.
      Lilium * formolongi is a lily hybrid that flowers within a year after sowing. We
      successfully identified four important stages during vegetative growth and
      flowering initiation of L. * formolongi under long day conditions. The plant
      tissues from the four stages were used in a genome-wide transcriptional analysis
      to investigate stage-specific changes of gene expression in L. * formolongi. In
      total, the sequence reads of the four RNA-sequencing libraries were assembled
      into 52,824 unigenes, of which 37,031 (70.10%) were differentially expressed. The
      global expression dynamics of the differentially expressed genes were predominant
      in flowering induction phase I and the floral differentiation stage, but down
      regulated in flowering induction phase II. Various transcription factor families
      relevant to flowering were elucidated, and the members of the MADS-box, SBP and
      CO-like transcription factor families were the most represented. There were 85
      differentially expressed genes relevant to flowering. CONSTANS-LIKE, FLOWERING
      LOCUS T, TREHALOSE-6-PHOSPHATE SYNTHASE and SQUAMOSA PROMOTER BINDING PROTEIN
      LIKE homologs were discovered and may play significant roles in the flowering
      induction and transition process of L. * formolongi. A putative gene regulatory
      network, including photoperiod, age-dependent and trehalose-6-phosphate flowering
      pathways, was constructed. This is the first expression dataset obtained from a
      transcriptome analysis of photoperiod-mediated flowering pathway in lily, and it
      is valuable for the exploration of the molecular mechanisms of flowering
      initiation and the short vegetative stage of L. * formolongi.

PMID- 28429255
TI  - Acute/subacute Neuro-Behcet's disease.

PMID- 28429253
TI  - Modified Metformin as a More Potent Anticancer Drug: Mitochondrial Inhibition,
      Redox Signaling, Antiproliferative Effects and Future EPR Studies.
AB  - Metformin, one of the most widely prescribed antidiabetic drugs in the world, is
      being repurposed as a potential drug in cancer treatment. Epidemiological studies
      suggest that metformin exerts anticancer effects in diabetic patients with
      pancreatic cancer. However, at typical antidiabetic doses the bioavailability of
      metformin is presumably too low to exert antitumor effects. Thus, more potent
      analogs of metformin are needed in order to increase its anticancer efficacy. To
      this end, a new class of mitochondria-targeted metformin analogs (or mito
      metformins) containing a positively-charged lipophilic triphenylphosphonium group
      was synthesized and tested for their antitumor efficacy in pancreatic cancer
      cells. Results indicate that the lead compound, mito-metformin10, was nearly 1000
      fold more potent than metformin in inhibiting mitochondrial complex I activity,
      inducing reactive oxygen species (superoxide and hydrogen peroxide) that
      stimulate redox signaling mechanisms, including the activation of
      adenosinemonophosphate kinase and inhibition of proliferation of pancreatic
      cancer cells. The potential use of the low-temperature electron paramagnetic
      resonance technique in assessing the role of mitochondrial complexes including
      complex I in tumor regression in response to metformin and mito-metformins in the
      in vivo setting is discussed.

PMID- 28429254
TI  - Biomarkers Predicting Bone Turnover in the Setting of CKD.
AB  - PURPOSE OF THE REVIEW: Impaired bone quality contributes to the increased
      fracture risk in chronic kidney disease patients. Both low and high turnover bone
      disease may compromise bone quality. The question arises whether bone biomarkers
      may be additive or replace bone histormorphometry for diagnosing the extremes of
      bone turnover. RECENT FINDINGS: Studies exploring the performance of established
      and emerging bone biomarkers against histomorphometric assessment of bone
      turnover are limited and overall yield inconclusive results as to their
      diagnostic utility. Bone biomarkers, although promising, currently fail to meet
      the needed diagnostic accuracy to replace bone histomorphometry and thus are not
      yet ready for clinical use. Bone biomarkers have not only several advantages, but
      also important limitations such as high biological variability, retention with
      kidney disease, preanalytical issues, and interassay variability. These important
      issues must be considered when developing and evaluating bone biomarkers. There
      is an urgent need for harmonization and standardization of available assays and
      additional bone biopsy studies.

PMID- 28429256
TI  - Dynamic Modeling of Problem Drinkers Undergoing Behavioral Treatment.
AB  - We use dynamical systems modeling to help understand how selected intra-personal
      factors interact to form mechanisms of behavior change in problem drinkers. Our
      modeling effort illustrates the iterative process of modeling using an
      individual's clinical data. Due to the lack of previous work in modeling behavior
      change in individual patients, we build our preliminary model relying on our
      understandings of the psychological relationships among the variables. This model
      is refined and the psychological understanding is then enhanced through the
      iterative modeling process. Our results suggest that this is a promising
      direction in research in alcohol use disorders as well as other behavioral
      sciences.

PMID- 28429257
TI  - Low-molecular-weight components of the metabolome control the proliferative
      activity in cellular and bacterial cultures.
AB  - The effects of blood metabolites and model cell culture exometabolites found in
      the human and animal blood metabolomes have been assessed. Specifically, the
      influence of carboxylic acids that are structural analogues of amino acids and
      the drug Aktoflor-C have been studied. Methods of organotypic culturing of rat
      tissues and Escherichia coli bacterial culturing have been used. It has been
      found that all the tested compounds either stimulate or inhibit cell
      proliferation in tissue cultures and proliferation in bacterial cultures. The
      metabolites that are present in blood and interstitial fluids can exert
      regulation effects on the tissues of the body and intestinal microbiota.

PMID- 28429258
TI  - Hormonal regulation of NK cell cytotoxic activity.
AB  - The effects of chorionic gonadotropin, estriol (E3), leptin, ghrelin, and
      kisspeptin on the intracellular expression of perforin, granzyme A, and granzyme
      B was studied in separated NK cells. All studied hormones except E3 are could
      modulate the expression of cytotoxic enzymes in NK cells by suppression of the
      expression of the most active proapoptotic agents, resulting in increased
      expression of granzyme A, which is typical of the decidual subpopulation of these
      lymphocytes.

PMID- 28429259
TI  - Early morphological and functional changes in the GABAergic system of hippocampus
      in the rat lithium-pilocarpine model of epilepsy.
AB  - We studied early alterations in the GABAergic system of the rat hippocampus in
      the lithium-pilocarpine model of epilepsy. Twenty-four hours after the
      pilocarpine treatment, a decrease in the number of calretinin-positive
      interneurons was observed in the CA1 field of the hippocampus, whereas the number
      of parvalbumin-positive interneurons remained unchanged. The decreased levels of
      the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and the membrane
      GABA transporter GAT1 were revealed using Western blot analysis. These data
      indicate an altered excitation/inhibition balance in the hippocampus with
      excitation dominance.

PMID- 28429260
TI  - The dietary patterns are a modifying risk factor for breast cancer: An ecological
      study.
AB  - A comparative study of dietary patterns (DPs) with breast cancer (BC) incidence
      in different countries has been performed. It was established that in the
      countries with a high incidence of BC (76 per 100 000 people) the levels of
      consumption of the "nutrients of animal foods," "fruits and beverages," and
      "alcoholic drinks" are 1.5-2 times higher and that of "cereals and vegetables" is
      1.5 times lower than in the countries with a low incidence of BC (35 per 100
      000). In Mediterranean countries, where incidence of BC is 51 per 100 000, the
      levels of consumption of "animal foods" is two times lower than the levels of
      consumption of "cereals and vegetables." A method of assessing the impact of DPs
      on the incidence of BC has been proposed.

PMID- 28429261
TI  - Localization of the dopamine receptors of types 1 and 2 on the bodies of POMC
      expressing neurons of the arcuate nucleus of the hypothalamus in mice and rats.
AB  - Using immunofluorescent techniques, we have demonstrated the presence of two main
      types of dopamine receptors, D1 and D2, on the bodies of neurons of the arcuate
      nucleus of the hypothalamus expressing the precursor of peptides of the
      melanocortin family proopiomelanocortin in C57Bl/6J mice and Wistar rats. These
      data show close functional relationship between the dopamine and melanocortin
      systems of the brain and involvement of dopamine in the control of synthesis and
      secretion of peptides of the melanocortin family.

PMID- 28429262
TI  - Movement of a female polar bear (Ursus maritimus) in the Kara Sea during the
      summer sea-ice break-up.
AB  - The polar bear movement trajectory in relation to onset date of the sea-ice break
      up was studied in the coastal zone of the Taimyr Peninsula, eastern part of the
      Kara Sea, using as an example a female polar bear tagged by a radio collar with
      an Argos satellite transmitter. Analysis of the long-term pattern of ice melting
      and tracking, by means of satellite telemetry, of the female polar bear who
      followed the ice-edge outgoing in the north-eastern direction (in summer 2012)
      suggests that direction of the polar bear movement depends precisely on the
      direction of the sea-ice cover break-up.

PMID- 28429263
TI  - Remote effects of short-term neonatal hyperthermia in Krushinsky-Molodkina rats
      prone to audiogenic seizures strain.
AB  - Using the audiogenic seizure prone Krushinsky-Molodkina rat strain, it was
      demonstrated that short-term (5 min) exposure of 14-day-old pups to an elevated
      temperature (42 degrees C) resulted in a significant decrease in audiogenic
      seizure severity at the age of 1 month. Presumably, this effect is determined by
      the activation of the heat-shock protein system (stress proteins).

PMID- 28429264
TI  - Lymphocytes incubated in the presence of IL-2 lose the capacity for chemotaxis
      but acquire antitumor activity.
AB  - Naive non-activated lymphocytes are capable of releasing the chemoattractant
      complex Tag7-Mts1 and can migrate along the gradient of its concentration. After
      activation of these cells by IL-2, they acquire the abilities to kill tumor cells
      and to release the cytotoxic Tag7-Hsp70 complex, which is accompanied by a loss
      of both the Tag7-Mts1-mediated lymphocyte chemotaxis and the ability to release
      this chemoattractant into the conditioned medium.

PMID- 28429265
TI  - Alternative approach to the treatment of diabetes mellitus.
AB  - The influence of insulin preparations (Actrapid and Ransulin) on the glucose and
      insulin blood level has been studied in patients with diabetes mellitus. It has
      been shown that comparable changes in the measured parameters are achieved in
      most patients with oral doses of Ransulin that are two to three times higher than
      the doses of Actrapid.

PMID- 28429266
TI  - CORR Insights(r): Does Extracellular DNA Production Vary in Staphylococcal
      Biofilms Isolated From Infected Implants versus Controls?

PMID- 28429267
TI  - Using air, soil and vegetation to assess the environmental behaviour of
      siloxanes.
AB  - This study aimed to contribute to the enhancement of the knowledge of levels,
      trends and behaviour of eight siloxanes (four linear and four cyclic) in the
      environment. Adding to the prioritised scrutiny of the incidence in the
      atmosphere through passive samplers (sorbent-impregnated polyurethane foam disks
      SIPs), the sampling of pine needles and soil was also performed, thus closing the
      circle of atmospheric exposure in the areas of study. Two sampling campaigns (one
      in summer and one in winter) were done in a total of eight sampling points in the
      Portuguese territory, which covered a wide range of human presence and land uses
      (urban, industrial, remote and beach areas). By adopting a "green" approach in
      terms of analytical methods, namely reducing the clean-up steps for the passive
      air samples and using the quick, easy, cheap, effective, rugged and safe
      (QuEChERS) technology for soils and pine needles, the results showed total
      concentration of siloxanes between 5 and 70 ng g-1 (dry weight) for soils and
      from 2 to 118 ng g-1 (dry weight (dw)) for pine needles, with no clear seasonal
      trend. For SIPs, the levels varied from 0.6 to 7.8 ng m-3 and were higher in
      summer than in winter in all sites. Overall, the cyclic siloxanes were found in
      much higher concentrations, with D5 and D6 being the most predominant in a great
      majority of cases. Also, the urban and industrial areas had the highest
      incidence, suggesting a strong anthropogenic fingerprint, in line with their main
      uses.

PMID- 28429268
TI  - Mutagenicity assessment of aerosols in emissions from domestic combustion
      processes.
AB  - Domestic biofuel combustion is one of the major sources of regional and local air
      pollution, mainly regarding particulate matter and organic compounds, during
      winter periods. Mutagenic and carcinogenic activity potentials of the ambient
      particulate matter have been associated with the fraction of polycyclic aromatic
      hydrocarbons (PAH) and their oxygenated (OPAH) and nitrogenated (NPAH)
      derivatives. This study aimed at assessing the mutagenicity potential of the
      fraction of this polycyclic aromatic compound in particles (PM10) from domestic
      combustion by using the Ames assays with Salmonella typhimurium TA98 and TA100.
      Seven biofuels, including four types of pellets and three agro-fuels (olive pit,
      almond shell and shell of pine nuts), were tested in an automatic pellet stove,
      and two types of wood (Pinus pinaster, maritime pine, and Eucalyptus globulus,
      eucalypt) were burned in a traditional wood stove. For this latter appliance, two
      combustion phases-Devolatilisation and flaming/smouldering-Were characterised
      separately. A direct-acting mutagenic effect for the devolatilisation phase of
      pine combustion and for both phases of eucalypt combustion was found. Almond
      shell revealed a weak direct-acting mutagenic effect, while one type of pellets,
      made of recycled wastes, and pine (devolatilisation) presented a cytotoxic effect
      towards strain TA100. Compared to themanually fired appliance, the automatic
      pellet stove promoted lower polyaromatic mutagenic emissions. For this device,
      only two of the studied biofuels presented a weak mutagenic or cytotoxic
      potential.

PMID- 28429269
TI  - Alternative carbon dioxide modelling approaches accounting for high residual
      gases in LandGEM.
AB  - High Canadian waste disposal rates necessitate landfill gas monitoring and
      accurate forecasting. CO2 estimates in LandGEM version 3.02 currently rest on the
      assumptions that CO2 is a function of CH4, where the two gases make up nearly
      100% of landfill gas content, leading to overestimated CO2 collection estimates.
      A total of 25 cases (five formulas, five approaches) compared annual CO2
      collection at four western Canadian landfills. Despite common use in literature,
      the 1:1 ratio of CH4 to CO2 was not recommended to forecast landfill gas
      collection in cold climates. The existing modelling approach significantly
      overestimated CO2 production in three of four sites, resulting in the highest
      residual sum of squares. Optimization resulted in the most accurate results for
      all formulas and approaches, which had the greatest reduction in residual sums of
      squares (RSS) over the default approach (60.1 to 97.7%). The 1.4 Ratio approach
      for L o:L o-CO2 yielded the second most accurate results for CO2 flow (mean RSS
      reduction of 50.2% for all sites and subsection models). The annual k-modified
      LandGEM calculated k's via two empirical formulas (based on precipitation) and
      yielded the lowest accuracy in 12 of 20 approaches. Unlike other studies, strong
      relationships between optimized annual k's and precipitation were not observed.

PMID- 28429270
TI  - Degradation of streptomycin in aquatic environment: kinetics, pathway, and
      antibacterial activity analysis.
AB  - Streptomycin used in human and veterinary medicine is released into the
      environment mainly through excretions. As such, its elimination in water should
      be investigated to control pollution. In this study, the degradation of
      streptomycin in water was studied, and the influence of variables, including
      light exposure, solution pH, temperature, ionic strength, dissolved organic
      matter (DOM), and coexisting surfactants, on degradation was investigated.
      Streptomycin degradation was consistent with the first-order model in aquatic
      environments. Its degradation rate under light exposure was 2.6-fold faster than
      that in the dark. Streptomycin was stable under neutral conditions, but it was
      easily decomposed in acidic and basic environments. Streptomycin degradation was
      enhanced by high temperature, and its half-life decreased from 103.4 days at 15 
      degrees C to 30.9 days at 40  degrees C. This process was also accelerated by the
      presence of Ca2+ and slightly improved by the addition of HA. Streptomycin
      degradation was suppressed by high levels of the cationic surfactant cetyltri-
      methylammonium bromide (CTAB), but was promoted by the anionic surfactant sodium
      dodecyl benzene sulfonate (SDBS). The main degradation intermediates/products
      were identified through liquid chromatography-mass spectrometry, and the possible
      degradation pathway was proposed. The antibacterial activity of streptomycin
      solution was also determined during degradation. Results showed that STR
      degradation generated intermediates/products with weaker antibacterial activity
      than the parent compound.

PMID- 28429271
TI  - Bisection method for accurate modeling and simulation of fouling in hollow fiber
      membrane system.
AB  - Accurate description and modeling of fouling on hollow fibers imposes a serious
      challenge to more effective fouling mitigation and performance optimization of
      the membrane system. Although the governing equations for membrane fouling can be
      constructed based on the known theories from membrane filtration and fluid
      dynamics, they are unsolvable analytically due to the complex spatially and
      temporally varying nature of fouling on hollow fibers. The current available
      numerical solutions for the governing equations are either unreliable or
      inconvenient to use because of the uses of unfounded assumptions or cumbersome
      calculation methods. This work presented for the first time a rigorous numerical
      procedure to solve the governing equations for fouling development on hollow
      fibers. A critical step to achieve the goal is the use of bisection method to
      determine the transmembrane pressure at the dead end of the fibers. With this
      procedure, fouling behavior in the hollow fiber membrane system under a given
      condition can be simulated within a second. The model simulations were well
      calibrated and verified with the published experimental data from literature.
      Also presented in the paper were simulations for performances of the hollow fiber
      membrane system under various operation conditions. Graphical abstract ?.

PMID- 28429272
TI  - Electrocatalytic dechlorination of 2,3,5-trichlorophenol on palladium/carbon
      nanotubes-nafion film/titanium mesh electrode.
AB  - Palladium/carbon nanotubes-nafion film-modified titanium mesh electrode (Pd/CNTs
      nafion film/Ti electrode) was prepared and used for catalytic dechlorination of
      2,3,5-trichlorophenol (2,3,5-TCP). The influences of factors, such as Pd2+
      concentration, plating solution pH, and electrodeposition time and current, on
      the preparation of the electrode were studied by cyclic voltammetry (CV) to
      establish the optimal electrode preparation conditions. Additionally, the CV
      results highlighted that the addition of the CNTs-nafion film could enhance the
      electrochemical performance of the electrode. The Pd/CNTs-nafion film/Ti
      electrode was characterized by field emission scanning electron microscopy
      (FESEM), X-ray diffraction (XRD), and inductively coupled plasma-atomic emission
      spectrometry (ICP-AES). The electrode exhibited good stability and high catalytic
      dechlorination capacity on 2,3,5-TCP-100 mg L-1 2,3,5-TCP was completely
      dechlorinated within 100 min at a dechlorination current of 5 mA and an initial
      solution pH of 2.3. High-performance liquid chromatography (HPLC) was used to
      detect the chlorinated phenolic intermediates, and the results revealed that the
      final products were mainly phenol. The kinetics studies revealed that the
      dechlorination of 2,3,5-TCP followed two-stage mixed order kinetics, and a
      possible degradation pathway for 2,3,5-TCP was proposed.

PMID- 28429273
TI  - Assessment of the temporal and spatial distribution of atmospheric PCNs and their
      air-soil exchange using passive air samplers in Shanghai, East China.
AB  - A total of 47 passive air samples and 25 soil samples were collected to study the
      temporal trend, distribution, and air-soil exchange of polychlorinated
      naphthalenes (PCNs) in Shanghai, China. Atmospheric PCNs ranged from 3.44 to 44.1
      pg/m3 (average of 21.9 pg/m3) in summer and 13.6 to 153 pg/m3 (average of 40.0
      pg/m3) in winter. In the soil samples, PCN concentrations were 54.7-1382 pg/g dry
      weight (average of 319 pg/g). Tri-CNs and tetra-CNs were two dominant homolog
      groups in air samples, while di-CNs were also found at comparable proportions to
      tri-CNs and tetra-CNs in soil samples. Most air and soil samples from the
      industrial and urban areas showed higher PCN concentrations than those from
      suburban areas. However, some soil samples in urban centers presented higher PCN
      concentrations than industrial areas. Analysis of PCN sources indicated that both
      industrial thermal process and historical usage of commercial PCN mixtures
      contributed to the PCN burden in most areas. The fugacity fraction results
      indicated a strong tendency of volatilization for lighter PCNs (tri- to hexa-CNs)
      in both seasons, and air-soil deposition for octa-CNs. Moreover, air-soil
      exchange fluxes indicate that soil was an important source of atmospheric PCNs in
      some areas. The results of this study provide information for use in the
      evaluation of the potential impact and human health risk of PCNs around the study
      areas.

PMID- 28429274
TI  - Retromer localizes to autophagosomes during HCV replication.

PMID- 28429275
TI  - TGF-beta1 Neuroprotection via Inhibition of Microglial Activation in a Rat Model
      of Parkinson's Disease.
AB  - Transforming growth factor (TGF)-beta1 is a pleiotropic cytokine with
      immunosuppressive and anti-inflammatory properties. Recently we have shown that
      TGF-beta1 pretreatment in vitro protects against 1-methyl-4-phenylpyridinium
      (MPP+)-induced dopaminergic neuronal loss that characterizes in Parkinson's
      disease (PD). Herein, we aimed to demonstrate that TGF-beta1 administration in
      vivo after MPP+ toxicity has neuroprotection that is achieved by a mediation of
      microglia. A rat model of PD was prepared by injecting MPP+ unilaterally in the
      striatum. At 14 days after MPP+ injection, TGF-beta1 was administrated in the
      right lateral cerebral ventricle. Primary ventral mesencephalic (VM) neurons and
      cerebral cortical microglia were treated by MPP+, respectively, and TGF-beta1 was
      applied to neuronal or microglial cultures at 1 h after MPP+ treatment. As
      expected, MPP+ resulted in decrease in TGF-beta1 production in the substantia
      nigra and in primary VM neurons and microglia. TGF-beta1 intracerebroventricular
      administration alleviated MPP+-induced PD-like changes in pathology, motor
      coordination and behavior. Meanwhile, TGF-beta1 ameliorated MPP+-induced
      microglial activation and inflammatory cytokine production in vivo.
      Interestingly, TGF-beta1 treatment was not able to ameliorate MPP+-induced
      dopaminergic neuronal loss and caspase-3/9 activation in mono-neuron cultures,
      but TGF-beta1 alleviated MPP+-induced microglial activation and inflammatory
      cytokine production in microglia-enriched cultures. This effect of TGF-beta1
      inhibiting microglial inflammatory response was blocked by Smad3 inhibitor SIS3.
      Importantly, neuronal exposure to supernatants of primary microglia that had been
      treated with TGF-beta1 reduced dopaminergic neuronal loss and caspase-3/9
      activation induced by MPP+-treated microglial supernatants. These findings
      establish that TGF-beta1 exerts neuroprotective property in PD by inhibiting
      microglial inflammatory response via Smad3 signaling.

PMID- 28429276
TI  - Enhancing thermal stability of a highly concentrated insulin formulation with
      Pluronic F-127 for long-term use in microfabricated implantable devices.
AB  - Development of highly concentrated formulations of protein and peptide drugs is a
      major challenge due to increased susceptibility to aggregation and precipitation.
      Numerous drug delivery systems including implantable and wearable controlled
      release devices require thermally stable formulations with high concentrations
      due to limited device sizes and long-term use. Herein we report a highly
      concentrated insulin gel formulation (up to 80 mg/mL, corresponding to 2200
      IU/mL), stabilized with a non-ionic amphiphilic triblock copolymer (i.e.,
      Pluronic F-127 (PF-127)). Chemical and physical stability of insulin was found to
      be improved with increasing polymer concentration, as evidenced by reduced
      insulin fibrillation, formation of degradation products, and preserved secondary
      structure as measured by HPLC and circular dichroism spectroscopy, respectively.
      This formulation exhibits excellent insulin stability for up to 30 days in vitro
      under conditions of continuous shear at 37  degrees C, attributable to the
      amphiphilic properties of the copolymer and increased formulation viscosity. The
      mechanism of stabilizing insulin structure by PF-127 was investigated by coarse
      grained molecular dynamics (CG-MD), all-atom MD, and molecular docking
      simulations. The computation results revealed that PF-127 could reduce
      fibrillation of insulin by stabilizing the secondary structure of unfolded
      insulin and forming hydrophobic interaction with native insulin. The gel
      formulations contained in microfabricated membrane-reservoir devices released
      insulin at a constant rate dependent on both membrane porosity and copolymer
      concentration. Subcutaneous implantation of the gel formulation-containing
      devices into diabetic rats resulted in normal blood glucose levels for the
      duration of drug release. These findings suggest that the thermally stable gel
      formulations are suitable for long-term and implantable drug delivery
      applications.

PMID- 28429277
TI  - Primary Ewing Sarcoma / Primitive Neuroectodermal Tumor of the Kidney: A
      Clinicopathologic Study of 23 Cases.
AB  - Primary Ewing sarcoma / primitive neuroectodermal tumor (ES) of the kidney is a
      rare neoplasm with limited clinicopathologic data. We report 23 such cases with
      no history of ES elsewhere in the body. The patients included 13 male and 10
      female, aged 8-70 years (mean, 31 years). The average tumor size was 11.7 cm
      (range, 5-20 cm). Microscopic analysis showed predominantly lobular growth (n =
      14), with focal papillary (n = 3), alveolar (n = 1), and hemangiopericytoma-like
      (n = 1) patterns. Several tumors (n = 11) exhibited robust mitotic activity (>10
      mitoses/10 high-power fields). Necrosis (n = 13) and lymphovascular invasion (n =
      14) were common. Homer Wright rosettes (n = 6) and perivascular pseudorosettes (n
      = 1) were also identified. The tumors invaded the renal sinus or perinephric fat
      (n = 11), renal vein (n = 13), and adrenal gland (n = 2). Molecular and
      fluorescence in situ hybridization analysis showed rearrangement of EWSR1 gene
      (10/10), associated with EWSR1-FLI1 gene fusion (7/10). All patients with follow
      up information (n = 18) had metastasis, commonly in the lungs (n = 12) and bone
      (n = 6). Twelve patients died of disease in a mean of 21 months; 6 patients were
      alive at a mean of 49 months after diagnosis. Primary kidney ES usually present
      at an advanced stage with extrarenal spread and metastasis. Although renal ES
      share histologic, immunohistochemical, and molecular features with their bone and
      soft tissue counterparts, they appear to be more aggressive tumors with poorer
      clinical outcome.

PMID- 28429278
TI  - [Trans-hepatico cystic coledochostomy for the opening hydatid cyst in the biliary
      tract: Indications and outcome evaluation of 25 cases].
AB  - The treatment of hydatid cysts of the liver opened in the bile ducts is sometimes
      difficult and complex. The trans-hepaticocystic coledochostomy (CTHK) is one of
      these processes. We conducted a review of the indications for this surgical
      procedure and its perioperative outcomes through a series of 25 patients and then
      we analyzed predictor factors of complications. During the period's study, 909
      patients with liver hydatid cyst went under the surgery. Ninety two (92, i.e.
      10.1%) of them had an opening in the bile ducts through a large fistula. Twenty
      five (25, i.e. 27%) had a trans-hepaticocystic coledochostomy. The sex ratio was
      0.6. The population was young with an average age of 47 years. The trans
      hepaticocystic coledochostomy was performed because of a thick pericyst
      associated with a nonsutured fistula in 18 cases, a voluminous residual cavity
      with a soft pericyst but the fistula was unexposed in six cases and in a case
      where the pericyst was thick, fistula was exposed. Its suture was associated with
      a high risk of bile duct stenosis. Specific morbidity was 20% due to a length of
      the intraductal coledochostomy under 2 cm (P = 0.016), the absence of an
      epiploplasty (P = 0.004) and the existence of a leak of contrast material outside
      the fistula on the cholangiography (P = 0.005). The trans-hepaticocystic
      coledochostomy is a safe and reliable technique, often indicated when other
      conservative methods are failing. The application of its technical requirements
      and avoidance of mounting errors allow reducing its morbidity.

PMID- 28429279
TI  - Improvement of lipid production by the oleaginous yeast Rhodosporidium toruloides
      through UV mutagenesis.
AB  - Oleaginous yeasts are considered a promising alternative lipid source for
      biodiesel fuel production. In this study, we attempted to improve the lipid
      productivity of the oleaginous yeast Rhodosporidium toruloides through UV
      irradiation mutagenesis and selection based on ethanol and H2O2 tolerance or
      cerulenin, a fatty acid synthetase inhibitor. Glucose consumption, cell growth,
      and lipid production of mutants were evaluated. The transcription level of genes
      involved in lipid production was also evaluated in mutants. The ethanol and H2O2
      tolerant strain 8766 2-31M and the cerulenin resistant strain 8766 3-11C were
      generated by UV mutagenesis. The 8766 2-31M mutant showed a higher lipid
      production rate, and the 8766 3-11C mutant produced a larger amount of lipid and
      had a higher lipid production rate than the wild type strain. Transcriptional
      analysis revealed that, similar to the wild type strain, the ACL1 and GND1 genes
      were expressed at significantly low levels, whereas IDP1 and ME1 were highly
      expressed. In conclusion, lipid productivity in the oleaginous yeast R.
      toruloides was successfully improved via UV mutagenesis and selection. The study
      also identified target genes for improving lipid productivity through gene
      recombination.

PMID- 28429282
TI  - Discriminating Malaria from Dengue Fever and Chikungunya Infection in Children
      Living in Endemic Areas.

PMID- 28429281
TI  - Impact of thyroid disease on testicular function.
AB  - INTRODUCTION: Testis was considered unresponsive to thyroid hormone for a long
      time. However, like in animals, the presence of thyroid hormone receptors in
      different testicular cell types was demonstrated also in humans. Accordingly,
      thyrotoxicosis and hypothyroidism have remarkable effects on testicular function
      and more extensively on fertility. REVIEW: Thyrotoxicosis and hypothyroidism are
      associated with changes affecting the endocrine, sexual, or reproductive
      functions. Particularly, compared with controls, hyperthyroid patients have
      higher serum SHBG and lower free and bioavailable testosterone concentrations, a
      higher rate of astheno-zoospermia, oligo-zoospermia, and terato-zoospermia, and a
      higher prevalence of sexual disturbances, such as premature ejaculation. In
      hypothyroid patients, hormonal changes are in the opposite direction compared
      with hyperthyroid patients. Thyroid hormone regulates a number of functions in
      the testis, such as proliferation and differentiations of non-germ cells,
      steroidogenesis, and sperm motility. Furthermore, thyroid hormone regulates
      testicular redox status. Consequently, thyroid hormone excess or deficiency can
      affect testicular function at different levels. CONCLUSIONS: In view of the high
      prevalence of thyrotoxicosis and hypothyroidism, a considerable part of infertile
      patients may harbor overt or subclinical thyroid disease. Identification and
      management of thyrotoxicosis/hypothyroidism associated infertility needs the
      collaboration of andrologists, endocrinologists, gynecologists, and general
      practitioners.

PMID- 28429280
TI  - Synergistic anti-cancer effects of epigenetic drugs on medulloblastoma cells.
AB  - PURPOSE: Medulloblastomas are aggressive brain malignancies. While considerable
      progress has been made in the treatment of medulloblastoma patients with respect
      to overall survival, these patients are still at risk of developing neurologic
      and cognitive deficits as a result of anti-cancer therapies. It is hypothesized
      that targeted molecular therapies represent a better treatment option for
      medulloblastoma patients. Therefore, the aim of the present study was to test a
      panel of epigenetic drugs for their effect on medulloblastoma cells under mild
      hypoxic conditions that reflect the physiological concentrations of oxygen in the
      brain. METHODS: Protein levels of histone deacetylase 1 (HDAC1) and DNA
      methyltransferase 1 (DNMT1) in medulloblastoma-derived cells (Daoy and D283 Med),
      as well as in developing and differentiated brain cells, were determined and
      compared. Class I and II histone deacetylase inhibitors (HDACi) and a DNMT
      inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), were applied to Daoy and D283 Med
      cells, and their effects were studied using viability, apoptosis and cancer
      sphere assays. RESULTS: We found that in HDAC1 and DNMT1 overexpressing
      medulloblastoma-derived cells, cell death was induced under various epigenetic
      drug conditions tested. At low HDACi concentrations, however, a pro-proliferative
      effect was observed. Parthenolide, a drug that affects cancer stem cells, was
      found to be efficient in inducing cell death in both cell lines tested. In
      contrast, we found that Daoy cells were more resistant to 5-aza-dC than D283 Med
      cells. When suberoylanilide hydroxamic acid (SAHA) and parthenolide were
      individually applied to both cell lines in combination with 5-aza-dC, a
      synergistic effect on cell survival was observed. CONCLUSIONS: Our current
      results suggest that the application of HDACi in combination with drugs that
      target DNMT may represent a promising option for the treatment of
      medulloblastoma.

PMID- 28429283
TI  - Use of Hormones, Tissue Factors and Bioengineering in the Management of
      Hypospadias.
AB  - Hypospadiology is a rapidly evolving field. Progress in the understanding of how
      hormonal therapy affects the growth of the phallus has allowed surgeons to
      optimize the tissues for surgery. But conflicting data from a number of studies
      and a lack of consensus on drugs, their dosing, mode of delivery and timing of
      use means that the creation of protocols is unlikely to happen in the near
      future. Nonetheless, there is a hope and the standardization of scientific
      reporting will make it easier to compare data at the global level. There are
      reports of the increasing incidence of hypospadias and the etiology is thought to
      be multifactorial. Although complex interactions between genetic polymorphisms
      and the environment make it difficult to identify the exact factors responsible
      for hypospadias, the advent of massively parallel gene sequencing, large scale
      epigenetic screens and CRISPR technology will definitely ease the process. The
      knowledge of culprit genes will not only broaden our understanding of embryology
      and growth but will also enable us to predict and/or modify tissue healing.
      Advances in tissue engineering are also expected to provide a plethora of
      biomaterials for urethral reconstruction. The development of this field is
      directly linked with the elucidation of the processes of proliferation and
      vascularization coupled with the cataloguing of the growth factors involved. One
      can safely conclude that the exciting new advances in the field will have far
      reaching consequences on patient care and counselling.

PMID- 28429284
TI  - Foxo1 Attenuates NaF-Induced Apoptosis of LS8 Cells through the JNK and
      Mitochondrial Pathways.
AB  - Fluoride-induced ameloblast apoptosis is a key event in dental fluorosis
      development. Forkhead box o1 (Foxo1) is a transcription factor involved in cell
      apoptosis. The present study aims to investigate the effect of Foxo1 on
      ameloblast apoptosis induced by fluoride in vitro and to explore its possible
      mechanism. Ameloblast-like cells (LS8 cells) were exposed to various
      concentrations of NaF for up to 48 h. Foxo1 activation was modulated using
      lentiviral vectors, and cell apoptosis was measured by flow cytometry. The
      expression levels of Foxo1, c-Jun N-terminal kinase (JNK), and some well-known
      regulators of the mitochondrial pathway of apoptosis (cytoplasmic cytochrome c,
      cleaved caspase-9, cleaved caspase-3, Bcl-2, and Bax) were detected by
      quantitative real-time PCR, western blot, and immunofluorescence assay. The
      results showed significantly decreased expression and increased phosphorylation
      of Foxo1 in NaF-treated LS8 cells. Further investigation revealed that forced
      Foxo1 activation with lentiviral vectors attenuated NaF-induced apoptosis of LS8
      cells, markedly decreasing protein levels of cytoplasmic cytochrome c, cleaved
      caspase-9, and cleaved caspase-3 while increasing the Bcl-2/Bax ratio and JNK
      expression level. These findings suggest that Foxo1 attenuated NaF-induced
      apoptosis of LS8 cells via inhibiting the mitochondrial pathway and activating
      JNK.

PMID- 28429285
TI  - The Organogermanium Compound Ge-132 Interacts with Nucleic Acid Components and
      Inhibits the Catalysis of Adenosine Substrate by Adenosine Deaminase.
AB  - Poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) is a water-soluble
      organogermanium compound that exerts various physiological effects, including
      anti-inflammatory activity and pain relief. In water, Ge-132 is hydrolyzed to 3
      (trihydroxygermyl)propanoic acid (THGP), which in turn is capable of interacting
      with cis-diol compounds through its trihydroxy group, indicating that this
      compound could also interact with diol-containing nucleic acid constituents. In
      this study, we evaluated the ability of THGP to interact with nucleosides or
      nucleotides via nuclear magnetic resonance (NMR) analysis. In addition, we
      evaluated the effect of added THGP on the enzymatic activity of adenosine
      deaminase (ADA) when using adenosine or 2'-deoxyadenosine as a substrate. In
      solution, THGP indeed formed complexes with nucleotides or nucleosides through
      their cis-diol group. Moreover, the ability of THGP to form complexes with
      nucleotides was influenced by the number of phosphate groups present on the
      ribose moiety. Notably, THGP also inhibited the catalysis of adenosine by ADA in
      a concentration-dependent manner. Thus, interactions between THGP and important
      biological nucleic acid constituents might be implicated in the physiological
      effects of Ge-132.

PMID- 28429286
TI  - Effects of Selenium Supplementation on the Diabetic Condition Depend on the
      Baseline Selenium Status in KKAy Mice.
AB  - Oxidative stress in obesity leads to insulin resistance in type 2 diabetes. Some
      selenoproteins possess antioxidant properties, suggesting that selenium (Se) may
      protect against type 2 diabetes; however, evidence from epidemiological studies
      is contradictory. We hypothesized that Se status before supplementation
      (baseline) contributes to the supplementation outcome. This study aimed to
      clarify the influence of baseline Se status on the effect of Se supplementation
      on the diabetic condition. Six-week-old KKAy mice were fed a diet without
      supplemental Se or with 0.1 ppm Se in the form of L-selenomethionine (SeM) for 2
      weeks to create low-Se and sufficient-Se baseline statuses, respectively. For the
      next 4 weeks, low-Se mice were given a SeM (0.5 ppm Se)-supplemented diet, and
      sufficient-Se mice were given either a SeM (0.5 ppm Se)- or sodium selenite (0.5
      ppm Se)-supplemented diet; control groups continued on baseline diets. Serum Se
      concentrations, glutathione peroxidase (GPx) activities, adiponectin levels,
      glucose tolerance, and insulin sensitivity were analyzed. All mice became
      diabetic during the 2-week baseline induction period. At the end of the
      supplementation period, Se-receiving groups demonstrated significantly higher Se
      concentrations and GPx activities than their respective controls. Sufficient-Se
      mice receiving SeM had lower blood glucose levels and better insulin sensitivity
      than control and sodium selenite-receiving mice, whereas low-Se mice receiving
      SeM showed no such improvements compared with their controls. Our results suggest
      that Se supplementation in the form of SeM may help prevent type 2 diabetes
      aggravation in people taking the 55 MUg/day Se recommended dietary allowance.

PMID- 28429287
TI  - Protective Effect of Selenoprotein X Against Oxidative Stress-Induced Cell
      Apoptosis in Human Hepatocyte (LO2) Cells via the p38 Pathway.
AB  - Oxidative stress, as mediated by ROS (reactive oxygen species), is a significant
      factor in initiating the cells damaged by affecting cellular macromolecules and
      impairing their biological functions; SelX, a selenoprotein also known as MsrB1
      belonging to the methionine sulfoxide reductase (Msr) family, is the redox
      repairing enzyme and involved in redox-related functions. In order to more
      precisely analyze the relationship between oxidative stress, cell oxidative
      damage, and SelX, we stably overexpressed porcine Selx full-length cDNA in human
      normal hepatocyte (LO2) cells. Cell viability, cell apoptosis rate, intracellular
      ROS, and the expression levels of mRNA or protein of apoptosis-related genes
      under H2O2-induced oxidative stress were detected. We found that overexpression
      of SelX can prevent the oxidative damage caused by H2O2 and propose that the main
      mechanism underlying the protective effects of SelX is the inhibition of LO2 cell
      apoptosis. The results revealed that overexpressed SelX reduced the H2O2-induced
      intracellular ROS generation, inhibited the H2O2-induced upregulation of Bax and
      downregulation of Bcl-2, and increased the mRNA and protein ratio of Bcl-2/Bax.
      Furthermore, it inhibited H2O2-induced p38 MAPK phosphorylation. Taken together,
      our findings suggested that SelX played important roles in protecting LO2 cells
      against oxidative damage and that its protective effect is partly via the p38
      pathway by acting as a ROS scavenger.

PMID- 28429288
TI  - Zika virus, a novel mosquito-borne congenital virus infection.

PMID- 28429289
TI  - The nature and consequences of cognitive deficits among tobacco smokers with HIV:
      a comparison to tobacco smokers without HIV.
AB  - HIV-infected smokers lose more years of life to tobacco-related disease than HIV.
      Since neurocognitive deficits are common among those with HIV and are associated
      with smoking persistence, these deficits may be a unique barrier to smoking
      cessation among HIV-infected smokers. Documenting unique differences in and
      correlates of cognition among HIV-infected smokers is a critical step towards
      developing a population-specific tobacco cessation treatment. We compared
      neurocognitive function between HIV-infected (n = 103) and HIV-uninfected smokers
      (n = 70), accounting for demographic and smoking-related variables. We also
      evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load,
      depression ratings, quality of life [QoL]) and HAART adherence were associated
      with cognition. Participants completed neurocognitive tasks (N-back and
      Continuous Performance Task [CPT]) measuring working memory, attention, and
      processing speed, and intra-individual variability. Stepwise regression models
      were conducted and validated with resampling techniques. HIV-infected smokers
      performed worse than HIV-uninfected smokers on working memory, processing speed,
      and intra-individual variability (all p < 0.01). ROC analysis for the model
      including cognitive measures demonstrated 85% area under the curve, which
      indicates "good prediction" for distinguishing between HIV-infected and HIV
      uninfected smokers. This was a significant improvement over the model including
      demographic and smoking-related variables only (p = 0.0003). Among HIV-infected
      smokers, neurocognitive performance was negatively associated with QoL and
      depression ratings. Smoking cessation interventions for HIV-infected smokers
      should consider cognitive neurorehabilitation as a potential strategy to decrease
      the likelihood of nicotine relapse and decrease tobacco-related morbidity in this
      population.

PMID- 28429291
TI  - Correlation of carotid blood flow and corrected carotid flow time with invasive
      cardiac output measurements.
AB  - BACKGROUND: Non-invasive measures that can accurately estimate cardiac output may
      help identify volume-responsive patients. This study seeks to compare two non
      invasive measures (corrected carotid flow time and carotid blood flow) and their
      correlations with invasive reference measurements of cardiac output. Consenting
      adult patients (n = 51) at Massachusetts General Hospital cardiac catheterization
      laboratory undergoing right heart catheterization between February and April 2016
      were included. Carotid ultrasound images were obtained concurrently with cardiac
      output measurements, obtained by the thermodilution method in the absence of
      severe tricuspid regurgitation and by the Fick oxygen method otherwise. Corrected
      carotid flow time was calculated as systole time/?cycle time. Carotid blood flow
      was calculated as pi * (carotid diameter)2/4 * velocity time integral * heart
      rate. Measurements were obtained using a single carotid waveform and an average
      of three carotid waveforms for both measures. RESULTS: Single waveform
      measurements of corrected flow time did not correlate with cardiac output (rho =
      0.25, 95% CI -0.03 to 0.49, p = 0.08), but an average of three waveforms
      correlated significantly, although weakly (rho = 0.29, 95% CI 0.02-0.53, p =
      0.046). Carotid blood flow measurements correlated moderately with cardiac output
      regardless of if single waveform or an average of three waveforms were used: rho
      = 0.44, 95% CI 0.18-0.63, p = 0.004, and rho = 0.41, 95% CI 0.16-0.62, p = 0.004,
      respectively. CONCLUSIONS: Carotid blood flow may be a better marker of cardiac
      output and less subject to measurements issues than corrected carotid flow time.

PMID- 28429290
TI  - Association of long-term patterns of depressive symptoms and attention/executive
      function among older men with and without human immunodeficiency virus.
AB  - Older HIV-infected men are at higher risk for both depression and cognitive
      impairments, compared to HIV-uninfected men. We evaluated the association between
      longitudinal patterns of depressive symptoms and attention/executive function in
      HIV-infected and HIV-uninfected men aged 50+ years to understand whether HIV
      infection influenced the long-term effect of depression on attention/executive
      function. Responses to the Center for Epidemiologic Studies-Depression scale and
      attention/executive function tests (Trail Making Test Part B and Symbol Digit
      Modalities Test) were collected semiannually from May 1986 to April 2015 in 1611
      men. Group-based trajectory models, stratified by HIV status, were used to
      identify latent patterns of depressive symptoms and attention/executive function
      across 12 years of follow-up. We identified three depression patterns for HIV
      infected and HIV-uninfected men (rare/never 50.0 vs. 60.6%, periodically
      depressed 29.6 vs. 24.5%, chronic high 20.5 vs.15.0%, respectively) and three
      patterns of attention/executive function for HIV-infected and HIV-uninfected men
      (worst-performing 47.4 vs. 45.1%; average 41.9 vs. 47.0%; best-performing 10.7
      vs. 8.0%, respectively). Multivariable logistic regression models were used to
      assess associations between depression patterns and worst-performing
      attention/executive function. Among HIV-uninfected men, those in the periodically
      depressed and chronic high depressed groups had higher odds of membership in the
      worst-performing attention/executive function group (adjusted odds ratio [AOR] =
      1.45, 95% CI 1.04, 2.03; AOR = 2.25, 95% CI 1.49, 3.39, respectively). Among HIV
      infected men, patterns of depression symptoms were not associated with patterns
      of attention/executive function. Results suggest that HIV-uninfected, but not HIV
      infected, men with chronic high depression are more likely to experience a long
      term pattern of attention/executive dysfunction.

PMID- 28429292
TI  - Preparation of Chloramphenicol/Amino Acid Combinations Exhibiting Enhanced
      Dissolution Rates and Reduced Drug-Induced Oxidative Stress.
AB  - Chloramphenicol is an old antibiotic agent that is re-emerging as a valuable
      alternative for the treatment of multidrug-resistant pathogens. However, it
      exhibits suboptimal biopharmaceutical properties and toxicity profiles. In this
      work, chloramphenicol was combined with essential amino acids (arginine,
      cysteine, glycine, and leucine) with the aim of improving its dissolution rate
      and reduce its toxicity towards leukocytes. The chloramphenicol/amino acid solid
      samples were prepared by freeze-drying method and characterized in the solid
      state by using Fourier transform infrared spectroscopy, powder X-ray diffraction,
      differential scanning calorimetry, scanning electron microscopy, and solid-state
      nuclear magnetic resonance. The dissolution properties, antimicrobial activity,
      reactive oxygen species production, and stability of the different samples were
      studied. The dissolution rate of all combinations was significantly increased in
      comparison to that of the pure active pharmaceutical ingredient. Additionally,
      oxidative stress production in human leukocytes caused by chloramphenicol was
      decreased in the chloramphenicol/amino acid combinations, while the antimicrobial
      activity of the antibiotic was maintained. The CAP:Leu binary combination
      resulted in the most outstanding solid system makes it suitable candidate for the
      development of pharmaceutical formulations of this antimicrobial agent with an
      improved safety profile.

PMID- 28429293
TI  - Topical Delivery of Fenoprofen Calcium via Elastic Nano-vesicular Spanlastics:
      Optimization Using Experimental Design and In Vivo Evaluation.
AB  - The aim of this study was to investigate the potential of surfactant-based
      nanovesicular system (spanlastics) for topical delivery of fenoprofen calcium
      (FPCa) to eliminate its oral gastrointestinal adverse effects. FPCa-loaded
      spanlastics were prepared by thin film hydration (TFH) technique according to a
      full factorial design to investigate the influence of formulation variables on
      the drug entrapment efficiency (%EE), particle size (PS), deformability index
      (DI), and the % drug released after 24 h through the cellulose membrane (Q24h)
      using Design-Expert(r) software. The optimized formula (composed of Span 60 and
      Tween 60 as an edge activator at weight ratio of 8: 2 in presence of Transcutol P
      as a cosolvent in the hydration media) exhibited the highest %EE (49.91 +/-
      2.60%), PS of 536.1 +/- 17.14 nm, DI of 5.07 +/- 0.06 g, and Q24h of 61.11 +/-
      2.70%; it was also characterized for morphology and physical stability. In vitro
      release study of FPCa-loaded spanlastic gel and conventional FPCa gel through a
      synthetic membrane and hairless rat skin were evaluated. The skin permeation
      study revealed that spanlastic gel exhibited both consistent and prolonged
      action. Finally, the % inhibition of carrageenan-induced rat paw edema of
      spanlastic gel was three times higher than the conventional FPCa gel after 24 h.
      In conclusion, spanlastic-based gel could be a great approach for improving
      topical delivery of fenoprofen calcium, providing both prolonged and enhanced
      anti-inflammatory activity in the treatment of arthritis.

PMID- 28429294
TI  - Ocular Cubosome Drug Delivery System for Timolol Maleate: Preparation,
      Characterization, Cytotoxicity, Ex Vivo, and In Vivo Evaluation.
AB  - Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and
      its primary treatment strategy is to lower IOP by medication. Current ocular drug
      delivery in treating glaucoma is confronting a variety of challenges, such as low
      corneal permeability and bioavailability due to the unique anatomical structure
      of the human eye. To tackle these challenges, a cubosome drug delivery system for
      glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM
      cubosomes (liquid crystalline nanoparticles) were prepared using glycerol
      monooleate and poloxamer 407 via high-pressure homogenization. These constructed
      nanoparticles appeared spherical using transmission electron microscopy and had
      an average particle size of 142 nm, zeta potential of -6.27 mV, and over 85%
      encapsulation efficiency. Moreover, using polarized light microscopy and small
      angle X-ray scattering (SAXS), it was shown that the TM cubosomes have cubic
      liquid crystalline D-type (Pn3m) structure, which provides good physicochemical
      stability and high encapsulation efficiency. Ex vivo corneal permeability
      experiments showed that the total amount of TM cubosomes penetrated was higher
      than the commercially available eye drops. In addition, in vivo studies revealed
      that TM cubosomes reduced the IOP in rabbits from 27.8~39.7 to 21.4~32.6 mmHg
      after 1-week administration and had a longer retention time and better lower-IOP
      effect than the commercial TM eye drops. Furthermore, neither cytotoxicity nor
      histological impairment in the rabbit corneas was observed. This study suggests
      that cubosomes are capable of increasing the corneal permeability and
      bioavailability of TM and have great potential for ocular disease treatment.

PMID- 28429295
TI  - Idiopathic benign paroxysmal positional vertigo in the elderly: a long-term
      follow-up study.
AB  - BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is the most common cause
      of peripheral-type vertigo in the elderly. While some studies have investigated
      BPPV among the elderly, no study has focused on the isolated idiopathic BPPV
      (iBPPV) in the elderly. AIMS: To investigate the clinical features and recurrence
      rate in elderly patients diagnosed with iBPPV. METHODS: The authors prospectively
      reviewed the medical records of 627 patients diagnosed with BPPV, and a total of
      370 patients fulfilled the inclusion criteria. The subjects were divided into two
      groups by age (experimental group >=65 years and control group 17-64 years), and
      the gender, numbers of canalith reposition maneuver (CRM) for successful
      treatment, time elapsed from onset of symptoms to clinic visit, the affected
      semicircular canal, and the 1- and 5-year recurrence proportion were analyzed.
      RESULTS: The gender, numbers of CRM for successful treatment, affected
      semicircular canal, and the 1- and 5-year recurrence proportion showed no
      statistically significant difference between two groups (p > 0.05). The only
      exception was the experimental group which took a longer duration from
      manifestation of symptoms to hospital visit than control group (student's t test,
      p = 0.021). DISCUSSION: Several previous studies report that the elderly with
      iBPPV shows more protracted clinical course and much higher recurrence rate than
      younger adult. Unlike those reports, our study showed no significant differences
      about the clinical features and recurrence rate between age groups. CONCLUSION:
      The elderly with iBPPV could be treated as effective as general population.

PMID- 28429296
TI  - Diurnal Changes in Transcript and Metabolite Levels during the Iron Deficiency
      Response of Rice.
AB  - BACKGROUND: Rice (Oryza sativa L.) is highly susceptible to iron (Fe) deficiency
      due to low secretion levels of the mugineic acid (MA) family phytosiderophore
      (PS) 2'-deoxymugineic acid (DMA) into the rhizosphere. The low levels of DMA
      secreted by rice have proved challenging to measure and, therefore, the pattern
      of DMA secretion under Fe deficiency has been less extensively studied relative
      to other graminaceous monocot species that secrete high levels of PS, such as
      barley (Hordeum vulgare L.). RESULTS: Gene expression and metabolite analyses
      were used to characterise diurnal changes occurring during the Fe deficiency
      response of rice. Iron deficiency inducible genes involved in root DMA
      biosynthesis and secretion followed a diurnal pattern with peak induction
      occurring 3-5 h after the onset of light; a result consistent with that of other
      Strategy II plant species such as barley and wheat. Furthermore, triple
      quadrupole mass spectrometry identified 3-5 h after the onset of light as peak
      time of DMA secretion from Fe-deficient rice roots. Metabolite profiling
      identified accumulation of amines associated with metal chelation, metal
      translocation and plant oxidative stress responses occurring with peak induction
      10-12 h after the onset of light. CONCLUSION: The results of this study confirmed
      that rice shares a similar peak time of Fe deficiency associated induction of DMA
      secretion compared to other Strategy II plant species but has less prominent
      daily fluctuations of DMA secretion. It also revealed metabolic changes
      associated with the remediation of Fe deficiency and mitigation of damage from
      resulting stress in rice roots. This study complements previous studies on the
      genetic changes in response to Fe deficiency in rice and constitutes an important
      advance towards our understanding of the molecular mechanisms underlying the rice
      Fe deficiency response.

PMID- 28429298
TI  - Peter John Derrick (1945-2017).

PMID- 28429297
TI  - Identification of QTLs for yield and agronomic traits in rice under stagnant
      flooding conditions.
AB  - BACKGROUND: Stagnant flooding, where water of 25-50 cm remains until harvest
      time, is a major problem in rainfed lowland areas. Most of the Sub1 varieties,
      which can withstand around 2 weeks of complete submergence, perform poorly in
      these conditions. Hence, varieties tolerant of stagnant flooding are essential.
      RESULTS: This paper presents the first study to map QTLs associated with
      tolerance to stagnant flooding, along with a parallel study under normal
      irrigation, using an F7 mapping population consisting of 148 RILs derived from a
      cross of Ciherang-Sub1 and the stagnant-flooding tolerant line IR10F365.
      Phenotypic data was collected for 15 key traits under both environments.
      Additionally, survival rate was measured under stress conditions. Genotyping was
      performed using the Illumina Infinium genotyping platform with a 6 K SNP chip,
      resulting in 469 polymorphic SNPs. Under stress and irrigated conditions, 38 and
      46 QTLs were identified, respectively. Clusters of QTLs were detected in both
      stress and normal conditions, especially on chromosomes 3 and 5. CONCLUSIONS:
      Unique and common QTLs were identified and their physiological consequences are
      discussed. These beneficial QTLs can be used as targets for molecular breeding
      and can be further investigated to understand the underlying molecular mechanisms
      involved in stagnant flooding tolerance in rice.

PMID- 28429299
TI  - Participation of C-H Protons in the Dissociation of a Proton Deficient Dipeptide.
AB  - The dissociation of anionic dipeptides Phe*Gly and GlyPhe*, where Phe* refers to
      sulfonated phenyl alanine, has been investigated by using ion trap mass
      spectrometry. The dipeptides undergo collision-induced dissociation (CID) to give
      the same products, indicating that they rearrange to a common structure before
      dissociation. The rearrangement does not occur with the dipeptide methyl esters.
      The structures of the b2 ions were investigated to determine the effect that
      having a remote, anionic site has on product formation. Comparison with the CID
      spectra for authentic structures shows that the b2 ion obtained from GlyPhe* has
      predominantly a diketopiperazine structure. The CID spectra for the Phe*Gly b2
      ion and the authentic oxazolone are similar, but differences in intensity suggest
      a two-component mixture. Isotopic labeling studies are consistent with the
      formation of two products, with one resulting from loss of a non-mobile proton on
      the Gly alpha-carbon. The results are attributed to the formation of an oxazole
      and oxazolone enol product. Electronic structure calculations predict that the
      enol structure of the Phe*Gly b2 ion is lower in energy than the keto version due
      to intramolecular hydrogen bonding with the sulfonate group. Graphical Abstract
      ?.

PMID- 28429300
TI  - Agroecology and Health: Lessons from Indigenous Populations.
AB  - PURPOSE OF REVIEW: The article aims to systematize and disseminate the main
      contributions of indigenous ancestral wisdom in the agroecological production of
      food, especially in Latin America. For this purpose, it is necessary to ask
      whether such knowledge can be accepted by academia research groups and
      international forums as a valid alternative that could contribute to overcome the
      world's nutritional problems. RECENT FINDINGS: Although no new findings are being
      made, the validity of ancestral knowledge and agroecology is recognized by
      scientific research, and by international forums organized by agencies of the
      United Nations. These recommend that governments should implement them in their
      policies of development, and in the allocation of funds to support these
      initiatives. Agroecology and ancestral knowledge are being adopted by a growing
      number of organizations, indigenous peoples and social groups in various parts of
      the world, as development alternatives that respond to local needs and
      worldviews. Its productive potential is progressively being recognized at an
      international level as a model that contributes to improve the condition of
      people regarding nutritional food.

PMID- 28429301
TI  - Ethical Issues Related to the Promotion of a "100 mSv Threshold Assumption" in
      Japan after the Fukushima Nuclear Accident in 2011: Background and Consequences.
AB  - PURPOSE OF REVIEW: This article describes the debates in Japan regarding the 100
      mSv threshold assumption and ethical issues related to it, and explores the
      background to distorted risk information and absence of risk communication in
      Japan. Then we seek proper risk communication based on scientific evidence.
      RECENT FINDINGS: On March 11, 2011 an accident occurred at the Fukushima Daiichi
      Nuclear Power Plant due to the Great East Japan Earthquake. Since then a number
      of misunderstandings have become common in Japan as a result of public statements
      by the Japanese and local governments that have no basis in medical science or
      are contradictory to medical science. Consequently, not only the population of
      Fukushima Prefecture, but also others, have been subjected to unnecessary
      exposure to radiation, against the As Low As Reasonably Achievable (ALARA)
      principle. The number of cases of thyroid cancer has increased by one or two
      orders of magnitude since the accident in Fukushima. However, the population has
      hardly been given any correct information from the central and local governments,
      medical societies, and media. The center of this problem is a statement on
      radiation-induced cancer (including thyroid cancer) made by the Japanese
      Government and Japanese medical academic societies indicating that "exposure of
      less than 100 mSv gives rise to no excess risk of cancer, and even if there is
      some resulting cancer it will be impossible to detect it" (this will be referred
      to as "the 100 mSv threshold assumption" from now onward). They have been saying
      this since April 2011 and have made no effort to correct it. Many Japanese began
      to notice this but correct information on radiation protection has reached only
      one part of the population. Risk communication should be based on scientific
      evidence, and providing it as information for the public is a key element. In
      Japan, governments and academic societies tried to communicate with the public
      without doing it. Ethical problems after the accident in Fukushima can be
      understood from the consequences of the mistakes in both risk information and
      risk communication in Japan after 2011.

PMID- 28429302
TI  - Ethics Guidelines in Environmental Epidemiology: Their Development and Challenges
      We Face.
AB  - PURPOSE OF REVIEW: This review integrates historical developments and key events
      in bringing ethics into epidemiology in general and into environmental
      epidemiology in particular. The goal is to provide context for and discern among
      the various approaches and motivations that drive the need for ethical conduct in
      support of the public interest. RECENT FINDINGS: The need for ethics guidelines
      in epidemiology is different from developments in other biomedical-related fields
      by virtue of its focus on populations rather than on individuals. The need for
      ethics guidelines in environmental epidemiology as a subspecialty of epidemiology
      stems from the larger scale of its mission than that of epidemiology per se.
      Ethics guidelines in the field of environmental epidemiology have been
      established. They articulate not only the profession's core values and mission,
      but more specifically, they address the environmental epidemiologist's
      obligations to the participants in research, to colleagues, and to employers.
      They are the product of consensus, scholarship, and diligent stewardship over
      several decades. The next challenge is ensuring their value and impact. The
      forces that support professional and institutional success, and the power of
      special interests, are the major threats to achieving the goals of ethical
      conduct and research for the public good. In environmental epidemiology, these
      threats have global implications.

PMID- 28429303
TI  - Natural Evolution of IgE Responses to Mite Allergens and Relationship to
      Progression of Allergic Disease: a Review.
AB  - PURPOSE OF REVIEW: Allergenic molecules of the house dust mite (HDM) are
      crucially important indoor allergens, contributing to allergic rhinitis and
      asthma around the globe. In the past years, recombinant molecules for diagnostics
      opened new pathways to investigate individual sensitization profiles and new
      chances for the prevention and treatment of HDM allergy. This review summarizes
      the latest findings on the evolution of IgE responses towards mite allergens.
      RECENT FINDINGS: Several cross-sectional and longitudinal studies confirmed the
      role of Der p 1 and Der p 2 as major allergenic proteins of the HDM. A newly
      identified player is the major allergen Der p 23. Apart from identifying the
      early sensitization towards this molecule as a risk factor for asthma in school
      age, a recent longitudinal study described sensitization patterns showing that
      the production of IgE usually starts towards a group of initiator proteins and
      may stay monomolecular or expand to an oligo- or even polymolecular stage. This
      phenomenon also correlates to clinical symptoms. A relation between a broad
      sensitization pattern and symptom severity has also been shown cross-sectionally.
      Individual sensitization profiles towards HDM allergens provide important
      information to evaluate a patient's current stage and risk for clinical symptoms.
      This knowledge paves the way for an early and adequate prevention and/or
      treatment.

PMID- 28429304
TI  - New Perspectives on the Diagnosis of Allergy to Anisakis spp.
AB  - PURPOSE OF REVIEW: To compare the prevalence of sensitization in different
      countries based on specific IgE values and to evaluate the use of isolated native
      or recombinant allergens for diagnosis. RECENT FINDINGS: Isolated allergens help
      in the diagnosis of truly sensitized patients avoiding false positives due to
      cross-reactions. Their use is therefore highly recommended, especially when used
      as a combination of several relevant allergens. The use of purified allergens
      allows an accurate diagnosis and this has led to three important findings: (1) in
      addition to the digestive route of sensitization, occupational and non-digestive
      exposure seems to be clinically relevant. (2) The parasite appears as an
      important agent for chronic urticaria. And (3) in endemic countries, the amount
      of highly sensitized subjects in the general population could be as high as 7%.
      Adequate information to asymptomatic patients on fish consumption habits would
      avoid new contacts with parasite allergens and decrease their specific IgE levels
      and consequently the appearance of acute or chronic episodes induced by the
      parasite.

PMID- 28429305
TI  - The Role of Macrolides in Chronic Rhinosinusitis (CRSsNP and CRSwNP).
AB  - PURPOSE OF REVIEW: We assess the literature on the pharmacokinetics, indications,
      important considerations, and effectiveness of long-term, low-dose macrolide
      antibiotics in chronic rhinosinusitis (CRS). RECENT FINDINGS: The key to
      effective implementation of macrolide therapy in CRS is appropriate patient
      selection. Macrolides have demonstrated the most benefit in Th1-mediated non
      eosinophilic CRS when used for durations of at least 3 months. Macrolide
      antibiotics have demonstrated great benefit when used for their anti-inflammatory
      or immunomodulatory properties, which include the blockage of pro-inflammatory
      cytokines, such as interleukin (IL)-8 and tumor necrosis factor-alpha (TNF
      alpha). They have been used in CRS patients not responding to traditional
      corticosteroid-based treatment regimens, but appear to be most effective
      specifically in Th1-mediated non-eosinophilic CRS in long durations and low
      doses. Further research is needed to better identify characteristics known to
      correlate with macrolide response so early directed therapy can be implemented.

PMID- 28429307
TI  - Emerging Approaches to Food Desensitization in Children.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight the recent advances
      in food desensitization in children with food allergy. RECENT FINDINGS: Recent
      advancements in epicutaneous, sublingual, and oral immunotherapy for food allergy
      in the future may offer children with food allergy and their families a viable
      option to reduce risk or severity of anaphylaxis with phase III trials ongoing
      for two of these treatment modalities. Food allergy prevalence in children is
      estimated to be up to 8%. These children are at risk of significant allergic
      reactions and anaphylaxis. Food avoidance and use of antihistamines or
      epinephrine has been the standard of care for these patients. This approach also
      has a significant socioeconomic effects on patients and their families. Recent
      advancements in understanding food allergy have allowed for exploring new methods
      of treatment. There is an increasing interest in oral immunotherapy, epicutaneous
      immunotherapy, or sublingual immunotherapy for food allergy. There have been also
      innovative approaches to immunotherapy by modification of food allergens (to make
      them less allergenic while maintain their immunogenicity) or adding adjunctive
      treatments (probiotics, anti-IgE, etc.) to increase efficacy or safety.

PMID- 28429306
TI  - Mitochondrial Function in Allergic Disease.
AB  - PURPOSE OF THE REVIEW: The connections between allergy, asthma and metabolic
      syndrome are becoming increasingly clear. Recent research suggests a unifying
      mitochondrial link between the diverse phenotypes of these interlinked
      morbidities. The scope of this review is to highlight cellular mechanisms,
      epidemiology and environmental allergens influencing mitochondrial function and
      its importance in allergy and asthma. We briefly also consider the potential of
      mitochondria-targeted therapies in prevention and cure. RECENT FINDINGS: Recent
      research has shown allergy, asthma and metabolic syndrome to be linked to
      mitochondrial dysfunction. Environmental pollutants and allergens are observed to
      cause mitochondrial dysfunction, primarily by inducing oxidative stress and ROS
      production. Malfunctioning mitochondria change the bioenergetics of the cell and
      its metabolic profile to favour systemic inflammation, which drives all three
      types of morbidities. Given the existing experimental evidence, approaches
      targeting mitochondria (e.g. antioxidant therapy and mitochondrial replacement)
      are being conducted in relevant disease models-with some progressing towards
      clinical trials, making mitochondrial function the focus of translational therapy
      research in asthma, allergy and linked metabolic syndrome.

PMID- 28429308
TI  - Chronic Candidiasis in Children.
AB  - PURPOSE OF REVIEW: Healthy children may develop candidal infections as the result
      of exposure to antibiotics or corticosteroids, but chronic candidiasis in
      children after the newborn period is unusual. Chronic mucocutaneous candidiasis
      (CMC) refers to a group of conditions characterized by recurrent or persistent
      infections with Candida species, particularly Candida albicans. CMC is a
      phenotype observed in a spectrum of immunologic disorders, some with
      endocrinologic and autoimmune features. RECENT FINDINGS: CMC can arise secondary
      to inherited or acquired T cell deficiencies, but in children is largely due to
      inborn errors impairing the dectin pathway and IL-17 immunity. We review the
      current understanding of the pathogenesis of chronic mucocutaneous candidiasis
      and discuss the immunologic pathways by which the immune system handles Candida.
      We highlight the historical and recent knowledge of CMC in children, emphasizing
      recent insights into basic science aspects of the dectin pathway, IL-17
      signaling, consequences of AIRE gene defects, and clinical aspects of
      inheritance, and features that distinguish the different syndromes. The clinical
      phenotype of CMC has many underlying genetic causes. Genetic testing is required
      for definitive diagnosis.

PMID- 28429309
TI  - alpha-Ketoadipic Acid and alpha-Aminoadipic Acid Cause Disturbance of
      Glutamatergic Neurotransmission and Induction of Oxidative Stress In Vitro in
      Brain of Adolescent Rats.
AB  - Tissue accumulation of alpha-ketoadipic (KAA) and alpha-aminoadipic (AAA) acids
      is the biochemical hallmark of alpha-ketoadipic aciduria. This inborn error of
      metabolism is currently considered a biochemical phenotype with uncertain
      clinical significance. Considering that KAA and AAA are structurally similar to
      alpha-ketoglutarate and glutamate, respectively, we investigated the in vitro
      effects of these compounds on glutamatergic neurotransmission in the brain of
      adolescent rats. Bioenergetics and redox homeostasis were also investigated
      because they represent fundamental systems for brain development and functioning.
      We first observed that AAA significantly decreased glutamate uptake, whereas
      glutamate dehydrogenase activity was markedly inhibited by KAA in a competitive
      fashion. In addition, AAA and more markedly KAA induced generation of reactive
      oxygen and nitrogen species (increase of 2',7'-dichloroflurescein (DCFH)
      oxidation and nitrite/nitrate levels), lipid peroxidation (increase of
      malondialdehyde concentrations), and protein oxidation (increase of carbonyl
      formation and decrease of sulfhydryl content), besides decreasing the antioxidant
      defenses (reduced glutathione (GSH)) and aconitase activity. Furthermore, KAA
      induced lipid peroxidation and GSH decrease were prevented by the antioxidants
      alpha-tocopherol, melatonin, and resveratrol, suggesting the involvement of
      reactive species in these effects. Noteworthy, the classical inhibitor of NMDA
      glutamate receptors MK-801 was not able to prevent KAA-induced and AAA-induced
      oxidative stress, determined by DCFH oxidation and GSH levels, making unlikely a
      secondary induction of oxidative stress through overstimulation of glutamate
      receptors. In contrast, KAA and AAA did not significantly change brain
      bioenergetic parameters. We speculate that disturbance of glutamatergic
      neurotransmission and redox homeostasis by KAA and AAA may play a role in those
      cases of alpha-ketoadipic aciduria that display neurological symptoms.

PMID- 28429310
TI  - The protective association of endogenous immunoglobulins against sepsis mortality
      is restricted to patients with moderate organ failure.
AB  - BACKGROUND: Pre-evaluation of endogenous immunoglobulin levels is a potential
      strategy to improve the results of intravenous immunoglobulins in sepsis, but
      more work has to be done to identify those patients who could benefit the most
      from this treatment. The objective of this study was to evaluate the impact of
      endogenous immunoglobulins on the mortality risk in sepsis depending on disease
      severity. METHODS: This was a retrospective observational study including 278
      patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming
      from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed
      into two groups depending on their Sequential Organ Failure Assessment score at
      ICU admission (SOFA < 8, n = 122 and SOFA >= 8, n = 156), and the association
      between immunoglobulin levels at ICU admission with mortality was studied in each
      group by Kaplan-Meier and multivariate logistic regression analysis. RESULTS:
      ICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to
      30.1/35.3% in the SOFA >= 8 group. In the group with SOFA < 8, the simultaneous
      presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was
      associated with a reduction in the survival mean time of 6.6 days in the first 28
      days and was a robust predictor of mortality risk either during the acute or
      during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for
      hospital mortality: 7.98). This predictive ability remained in the absence of
      prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality:
      5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent
      predictor of ICU mortality in this group. In contrast, in the SOFA >= 8 group, we
      found no immunoglobulin thresholds associated with neither ICU nor hospital
      mortality. CONCLUSIONS: Endogenous immunoglobulin levels may have a different
      impact on the mortality risk of sepsis patients based on their severity. In
      patients with moderate organ failure, the simultaneous presence of low levels of
      IgG, IgA and IgM was a consistent predictor of both acute and post-acute
      mortalities.

PMID- 28429311
TI  - Improving animal welfare using continuous nalbuphine infusion in a long-term rat
      model of sepsis.
AB  - BACKGROUND: Sepsis research relies on animal models to investigate the mechanisms
      of the dysregulated host response to infection. Animal welfare concerns request
      the use of potent analgesics for the Refinement of existing sepsis models,
      according to the 3Rs principle. Nevertheless, adequate analgesia is often
      missing, partly because the effects of analgesics in this particular condition
      are unknown. We evaluated the use of nalbuphine, an opioid with kappa agonistic
      and mu antagonistic effects, in rats with and without experimental sepsis.
      METHODS: Male Wistar rats were anesthetized with isoflurane and instrumented with
      a venous line for drug administration. Arterial cannulation allowed for blood
      pressure measurements and blood sampling in short-term experiments of non-septic
      animals. Nalbuphine (or placebo) was administered intravenously at a dose of 1
      mg/kg/h. Long-term (48 h) experiments in awake septic animals included repetitive
      clinical scoring with the Rat Grimace Scale and continuous heart rate monitoring
      by telemetry. Sepsis was induced by intraperitoneal injection of faecal slurry.
      Nalbuphine plasma levels were measured by liquid chromatography-high resolution
      mass spectrometry. RESULTS: In anesthetized healthy animals, nalbuphine led to a
      significant reduction of respiratory rate, heart rate, and mean arterial pressure
      during short-term experiments. In awake septic animals, a continuous nalbuphine
      infusion did not affect heart rate but significantly improved the values of the
      Rat Grimace Scale. Nalbuphine plasma concentrations remained stable between 4 and
      24 h of continuous infusion in septic rats. CONCLUSIONS: In anaesthetised rats,
      nalbuphine depresses respiratory rate, heart rate, and blood pressure. In awake
      animals, nalbuphine analgesia improves animal welfare during sepsis.

PMID- 28429312
TI  - SOX11 regulates the pro-apoptosis signal pathway and predicts a favorable
      prognosis of mantle cell lymphoma.
AB  - Sex-determining region Y-box 11 (SOX11) is an important diagnostic marker in
      mantle cell lymphoma (MCL). However, the direct oncogenic mechanisms and
      downstream effector pathways implicated in SOX11-driven transformation remain
      poorly understood. In the present study, we analyzed SOX11 expression in B-NHL,
      and used lentivirus-mediated RNA interference targeting SOX11 to investigate the
      resulting changes in cellular processes and the underlying mechanisms in MCL cell
      lines. We found that patients with higher SOX11 expression have superior overall
      survival (OS) and progression-free survival (PFS) compared to those with lower
      SOX11 expression. SOX11 silencing promotes proliferation and inhibiting apoptosis
      of MCL cell through caspase-9-3-7-PARP signaling, and desensitizes MCL cell to
      bortezomib. Conclusively, our data suggest that SOX11 represents a useful
      prognostic marker in mantle cell lymphoma.

PMID- 28429313
TI  - Gradually shrinking intra-abdominal desmoid tumor derived from the stomach in a
      young boy: a case report.
AB  - BACKGROUND: Intra-abdominal desmoid tumors, particularly those derived from the
      stomach, are rare. Such tumors are associated with a history of familial
      adenomatous polyposis (FAP), trauma, or surgical procedures in general. In
      addition, spontaneous shrinking of an intra-abdominal desmoid tumor is rarer. And
      desmoid tumors most commonly arise during the fourth decade of life. CASE
      PRESENTATION: A 17-year-old boy with lower abdominal pain was diagnosed with a
      gastrointestinal stromal tumor (GIST) or a hematoma at a local hospital. He had
      no history of FAP, trauma, or previous surgery. Abdominal computed tomography
      (CT) was performed for observational purposes three times over a 9-month period.
      The tumor gradually decreased in size over time; however, the tumor did not
      shrink sufficiently to be diagnosed as a hematoma. Because there was a high
      possibility of a GIST from the stomach, he underwent laparotomy. Operative
      findings revealed that the tumor was a hard mass firmly attached to both the
      greater curvature of the stomach and the inferior pole of the spleen.
      Pathologically, the tumor was diagnosed as a desmoid tumor derived from the
      stomach. CONCLUSION: For a young boy without a history of FAP, trauma, or
      surgical procedures, it is difficult to define an intra-abdominal tumor near the
      stomach as a desmoid tumor. In such cases, surgical resection is recommended for
      a definitive diagnosis.

PMID- 28429314
TI  - Evolutionary Origin of Euglena.
AB  - Euglenids (Excavata, Discoba, Euglenozoa, Euglenida) is a group of free-living,
      single-celled flagellates living in the aquatic environments. The uniting and
      unique morphological feature of euglenids is the presence of a cell covering
      called the pellicle. The morphology and organization of the pellicle correlate
      well with the mode of nutrition and cell movement. Euglenids exhibit diverse
      modes of nutrition, including phagotrophy and photosynthesis. Photosynthetic
      species (Euglenophyceae) constitute a single subclade within euglenids. Their
      plastids embedded by three membranes arose as the result of a secondary
      endosymbiosis between phagotrophic eukaryovorous euglenid and the Pyramimonas
      related green alga. Within photosynthetic euglenids three evolutionary lineages
      can be distinguished. The most basal lineage is formed by one mixotrophic
      species, Rapaza viridis. Other photosynthetic euglenids are split into two
      groups: predominantly marine Eutreptiales and freshwater Euglenales. Euglenales
      are divided into two families: Phacaceae, comprising three monophyletic genera
      (Discoplastis, Lepocinclis, Phacus) and Euglenaceae with seven monophyletic
      genera (Euglenaformis, Euglenaria, Colacium, Cryptoglena, Strombomonas,
      Trachelomonas, Monomorphina) and polyphyletic genus Euglena. For 150 years
      researchers have been studying Euglena based solely on morphological features
      what resulted in hundreds of descriptions of new taxa and many artificial intra
      generic classification systems. In spite of the progress towards defining
      Euglena, it still remains polyphyletic and morphologically almost
      undistinguishable from members of the recently described genus Euglenaria;
      members of both genera have cells undergoing metaboly (dynamic changes in cell
      shape), large chloroplasts with pyrenoids and monomorphic paramylon grains. Model
      organisms Euglena gracilis Klebs, the species of choice for addressing
      fundamental questions in eukaryotic biochemistry, cell and molecular biology, is
      a representative of the genus Euglena.

PMID- 28429315
TI  - The Mitochondrion of Euglena gracilis.
AB  - In the presence of oxygen, Euglena gracilis mitochondria function much like
      mammalian mitochondria. Under anaerobiosis, E. gracilis mitochondria perform a
      malonyl-CoA independent synthesis of fatty acids leading to accumulation of wax
      esters, which serve as the sink for electrons stemming from glycolytic ATP
      synthesis and pyruvate oxidation. Some components (enzymes and cofactors) of
      Euglena's anaerobic energy metabolism are found among the anaerobic mitochondria
      of invertebrates, others are found among hydrogenosomes, the H2-producing
      anaerobic mitochondria of protists.

PMID- 28429316
TI  - C2 metabolism in Euglena.
AB  - Euglenoids are able to assimilate fatty acids and alcohols with various carbon
      chain lengths, and ethanol is known to be one of the best carbon sources to
      support the growth of Euglena gracilis. Ethanol is first oxidized to acetate by
      the sequential reactions of alcohol dehydrogenase and acetaldehyde dehydrogenase
      in the mitochondria, and then converted to acetyl coenzyme A (acetyl-CoA). Acetyl
      CoA is metabolized through the glyoxylate cycle which is a modified tricarboxylic
      acid (TCA) cycle in which isocitrate lyase (ICL) and malate synthase (MS)
      function to bypass the two decarboxylation steps of the TCA cycle, enabling the
      net synthesis of carbohydrates from C2 compounds. ICL and MS form a unique
      bifunctional enzyme localized in Euglena mitochondria, not in glyoxysome as in
      other eukaryotes. The unique glyoxylate and glycolate metabolism during
      photorespiration is also discussed in this chapter.

PMID- 28429317
TI  - Biochemistry and Physiology of Reactive Oxygen Species in Euglena.
AB  - Reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are by
      products of various metabolic processes in aerobic organisms including Euglena.
      Chloroplasts and mitochondria are the main sites of ROS generation by
      photosynthesis and respiration, respectively, through the active electron
      transport chain. An efficient antioxidant network is required to maintain
      intracellular ROS pools at optimal conditions for redox homeostasis. A comparison
      with the networks of plants and animals revealed that Euglena has acquired some
      aspects of ROS metabolic process. Euglena lacks catalase and a typical
      selenocysteine containing animal-type glutathione peroxidase for hydrogen
      peroxide scavenging, but contains enzymes involved in ascorbate-glutathione cycle
      solely in the cytosol. Ascorbate peroxidase in Euglena, which plays a central
      role in the ascorbate-glutathione cycle, forms a unique intra-molecular dimer
      structure that is related to the recognition of peroxides. We recently identified
      peroxiredoxin and NADPH-dependent thioredoxin reductase isoforms in cellular
      compartments including chloroplasts and mitochondria, indicating the
      physiological significance of the thioredoxin system in metabolism of ROS.
      Besides glutathione, Euglena contains the unusual thiol compound trypanothione,
      an unusual form of glutathione involving two molecules of glutathione joined by a
      spermidine linker, which has been identified in pathogenic protists such as
      Trypanosomatida and Schizopyrenida. Furthermore, in contrast to plants,
      photosynthesis by Euglena is not susceptible to hydrogen peroxide because of
      resistance of the Calvin cycle enzymes fructose-1,6-bisphosphatse, NADP+
      glyceraldehyde-3-phosphatase, sedoheptulose-1,7-bisphosphatase, and
      phosphoribulokinase to hydrogen peroxide. Consequently, these characteristics of
      Euglena appear to exemplify a strategy for survival and adaptation to various
      environmental conditions during the evolutionary process of euglenoids.

PMID- 28429318
TI  - Biochemistry and Physiology of Vitamins in Euglena.
AB  - Euglena gracilis Z requires vitamins B1 and B12 for growth. It takes up and
      accumulates large amounts of these exogenous vitamins through energy-dependent
      active transport systems. Except for these essential vitamins, E. gracilis Z has
      the ability to synthesize all human vitamins. Euglena synthesizes high levels of
      antioxidant vitamins such as vitamins C and E, and, thus, are used as nutritional
      supplements for humans and domestic animals. Methods to effectively produce
      vitamins in Euglena have been investigated.Previous biochemical studies indicated
      that E. gracilis Z contains several vitamin-related novel synthetic enzymes and
      metabolic pathways which suggests that it is a highly suitable organism for
      elucidating the physiological functions of vitamins in comparative biochemistry
      and biological evolution. E. gracilis Z has an unusual biosynthetic pathway for
      vitamin C, a hybrid of the pathways found in animals and plants. This chapter
      presents up-to-date information on the biochemistry and physiological functions
      of vitamins in this organism.

PMID- 28429319
TI  - Biochemistry and Physiology of Heavy Metal Resistance and Accumulation in
      Euglena.
AB  - Free-living microorganisms may become suitable models for removal of heavy metals
      from polluted water bodies, sediments, and soils by using and enhancing their
      metal accumulating abilities. The available research data indicate that protists
      of the genus Euglena are a highly promising group of microorganisms to be used in
      bio-remediation of heavy metal-polluted aerobic and anaerobic acidic aquatic
      environments. This chapter analyzes the variety of biochemical mechanisms evolved
      in E. gracilis to resist, accumulate and remove heavy metals from the
      environment, being the most relevant those involving (1) adsorption to the
      external cell pellicle; (2) intracellular binding by glutathione and glutathione
      polymers, and their further compartmentalization as heavy metal-complexes into
      chloroplasts and mitochondria; (3) polyphosphate biosynthesis; and (4) secretion
      of organic acids. The available data at the transcriptional, kinetic and
      metabolic levels on these metabolic/cellular processes are herein reviewed and
      analyzed to provide mechanistic basis for developing genetically engineered
      Euglena cells that may have a greater removal and accumulating capacity for
      bioremediation and recycling of heavy metals.

PMID- 28429320
TI  - Euglena gracilis Genome and Transcriptome: Organelles, Nuclear Genome Assembly
      Strategies and Initial Features.
AB  - Euglena gracilis is a major component of the aquatic ecosystem and together with
      closely related species, is ubiquitous worldwide. Euglenoids are an important
      group of protists, possessing a secondarily acquired plastid and are relatives to
      the Kinetoplastidae, which themselves have global impact as disease agents. To
      understand the biology of E. gracilis, as well as to provide further insight into
      the evolution and origins of the Kinetoplastidae, we embarked on sequencing the
      nuclear genome; the plastid and mitochondrial genomes are already in the public
      domain. Earlier studies suggested an extensive nuclear DNA content, with likely a
      high degree of repetitive sequence, together with significant extrachromosomal
      elements. To produce a list of coding sequences we have combined transcriptome
      data from both published and new sources, as well as embarked on de novo
      sequencing using a combination of 454, Illumina paired end libraries and long
      PacBio reads. Preliminary analysis suggests a surprisingly large genome
      approaching 2 Gbp, with a highly fragmented architecture and extensive repeat
      composition. Over 80% of the RNAseq reads from E. gracilis maps to the assembled
      genome sequence, which is comparable with the well assembled genomes of T. brucei
      and T. cruzi. In order to achieve this level of assembly we employed multiple
      informatics pipelines, which are discussed here. Finally, as a preliminary view
      of the genome architecture, we discuss the tubulin and calmodulin genes, which
      highlight potential novel splicing mechanisms.

PMID- 28429321
TI  - Euglena Transcript Processing.
AB  - RNA transcript processing is an important stage in the gene expression pathway of
      all organisms and is subject to various mechanisms of control that influence the
      final levels of gene products. RNA processing involves events such as nuclease
      mediated cleavage, removal of intervening sequences referred to as introns and
      modifications to RNA structure (nucleoside modification and editing). In Euglena,
      RNA transcript processing was initially examined in chloroplasts because of
      historical interest in the secondary endosymbiotic origin of this organelle in
      this organism. More recent efforts to examine mitochondrial genome structure and
      RNA maturation have been stimulated by the discovery of unusual processing
      pathways in other Euglenozoans such as kinetoplastids and diplonemids. Eukaryotes
      containing large genomes are now known to typically contain large collections of
      introns and regulatory RNAs involved in RNA processing events, and Euglena
      gracilis in particular has a relatively large genome for a protist. Studies
      examining the structure of nuclear genes and the mechanisms involved in nuclear
      RNA processing have revealed that indeed Euglena contains large numbers of
      introns in the limited set of genes so far examined and also possesses large
      numbers of specific classes of regulatory and processing RNAs, such as small
      nucleolar RNAs (snoRNAs). Most interestingly, these studies have also revealed
      that Euglena possesses novel processing pathways generating highly fragmented
      cytosolic ribosomal RNAs and subunits and non-conventional intron classes removed
      by unknown splicing mechanisms. This unexpected diversity in RNA processing
      pathways emphasizes the importance of identifying the components involved in
      these processing mechanisms and their evolutionary emergence in Euglena species.

PMID- 28429322
TI  - Photo and Nutritional Regulation of Euglena Organelle Development.
AB  - Euglena can use light and CO2, photosynthesis, as well as a large variety of
      organic molecules as the sole source of carbon and energy for growth. Light
      induces the enzymes, in this case an entire organelle, the chloroplast, that is
      required to use CO2 as the sole source of carbon and energy for growth. Ethanol,
      but not malate, inhibits the photoinduction of chloroplast enzymes and induces
      the synthesis of the glyoxylate cycle enzymes that comprise the unique metabolic
      pathway leading to two carbon, ethanol and acetate, assimilation. In resting,
      carbon starved cells, light mobilizes the degradation of the storage carbohydrate
      paramylum and transiently induces the mitochondrial proteins required for the
      aerobic metabolism of paramylum to provide the carbon and energy required for
      chloroplast development. Other mitochondrial proteins are degraded upon light
      exposure providing the amino acids required for the synthesis of light induced
      proteins. Changes in protein levels are due to increased and decreased rates of
      synthesis rather than changes in degradation rates. Changes in protein synthesis
      rates occur in the absence of a concomitant increase in the levels of mRNAs
      encoding these proteins indicative of photo and metabolic control at the
      translational rather than the transcriptional level. The fraction of mRNA
      encoding a light induced protein such as the light harvesting chlorophyll a/b
      binding protein of photosystem II, (LHCPII) associated with polysomes in the dark
      is similar to the fraction associated with polysomes in the light indicative of
      photoregulation at the level of translational elongation. Ethanol, a carbon
      source whose assimilation requires carbon source specific enzymes, the glyoxylate
      cycle enzymes, represses the synthesis of chloroplast enzymes uniquely required
      to use light and CO2 as the sole source of carbon and energy for growth. The
      catabolite sensitivity of chloroplast development provides a mechanism to
      prioritize carbon source utilization. Euglena uses all of its resources to
      develop the metabolic capacity to utilize carbon sources such as ethanol which
      are rarely in the environment and delays until the rare carbon source is no
      longer available forming the chloroplast which is required to utilize the
      ubiquitous carbon source, light and CO2.

PMID- 28429323
TI  - Protein Targeting to the Plastid of Euglena.
AB  - The lateral transfer of photosynthesis between kingdoms through endosymbiosis is
      among the most spectacular examples of evolutionary innovation. Euglena, which
      acquired a chloroplast indirectly through an endosymbiosis with a green alga,
      represents such an example. As with other endosymbiont-derived plastids from
      eukaryotes, there are additional membranes that surround the organelle, of which
      Euglena has three. Thus, photosynthetic genes that were transferred from the
      endosymbiont to the host nucleus and whose proteins are required in the new
      plastid, are now faced with targeting and plastid import challenges. Early
      immunoelectron microscopy data suggested that the light-harvesting complexes,
      photosynthetic proteins in the thylakoid membrane, are post-translationally
      targeted to the plastid via the Golgi apparatus, an unexpected discovery at the
      time. Proteins targeted to the Euglena plastid have complex, bipartite
      presequences that direct them into the endomembrane system, through the Golgi
      apparatus and ultimately on to the plastid, presumably via transport vesicles.
      From transcriptome sequencing, dozens of plastid-targeted proteins were
      identified, leading to the identification of two different presequence
      structures. Both have an amino terminal signal peptide followed by a transit
      peptide for plastid import, but only one of the two classes of presequences has a
      third domain-the stop transfer sequence. This discovery implied two different
      transport mechanisms; one where the protein was fully inserted into the lumen of
      the ER and another where the protein remains attached to, but effectively
      outside, the endomembrane system. In this review, we will discuss the biochemical
      and bioinformatic evidence for plastid targeting, discuss the evolution of the
      targeting system, and ultimately provide a working model for the targeting and
      import of proteins into the plastid of Euglena.

PMID- 28429324
TI  - Photomovement in Euglena.
AB  - Motile microorganisms such as the green Euglena gracilis use a number of external
      stimuli to orient in their environment. They respond to light with photophobic
      responses, photokinesis and phototaxis, all of which can result in accumulations
      of the organisms in suitable habitats. The light responses operate
      synergistically with gravitaxis, aerotaxis and other responses. Originally the
      microscopically obvious stigma was thought to be the photoreceptor, but later the
      paraxonemal body (PAB, paraflagellar body) has been identified as the light
      responsive organelle, located in the trailing flagellum inside the reservoir. The
      stigma can aid in light direction perception by shading the PAB periodically when
      the cell rotates helically in lateral light, but stigmaless mutants can also
      orient with respect to the light direction, and negative phototaxis does not need
      the presence of the stigma. The PAB is composed of dichroically oriented
      chromoproteins which is reflected in a pronounced polarotaxis in polarized light.
      There was a long debate about the potential photoreceptor molecule in Euglena,
      including carotenoids, flavins and rhodopsins. This discussion was terminated by
      the unambiguous proof that the photoreceptor is a 400 kDa photoactivated adenylyl
      cyclase (PAC) which consists of two alpha- and two beta-subunits each. Each
      subunit possesses two BLUF (Blue Light receptor Using FAD) domains binding FAD,
      which harvest the light energy, and two adenylyl cyclases, which produce cAMP
      from ATP. The cAMP has been found to activate one of the five protein kinase s
      found in Euglena (PK.4). This enzyme in turn is thought to phosphorylate proteins
      inside the flagellum which result in a change in the flagellar beating pattern
      and thus a course correction of the cell. The involvements of PAC and protein
      kinase have been confirmed by RNA interference (RNAi). PAC is responsible for
      step-up photophobic responses as well as positive and negative phototaxis, but
      not for the step-down photophobic response, even though the action spectrum of
      this resembles those for the other two responses. Analysis of several colorless
      Euglena mutants and the closely related Euglena longa (formerly Astasia longa)
      confirms the results. Photokinesis shows a completely different action spectrum.
      Some other Euglena species, such as E. sanguinea and the gliding E. mutabilis,
      have been investigated, again showing totally different action spectra for
      phototaxis and photokinesis as well as step-up and step-down photophobic
      responses.

PMID- 28429325
TI  - Gravitaxis in Euglena.
AB  - Motile microorganisms utilize a number of responses to external stimuli including
      light, temperature, chemicals as well as magnetic and electric fields. Gravity is
      a major clue to select a niche in their environment. Positive gravitaxis leads an
      organism down into the water column and negative gravitaxis brings it to the
      surface. In Euglena the precision of gravitaxis is regulated by an internal
      rhythm entrained by the daily light/dark cycle. This and the cooperation with
      phototaxis bring the cells into an optimal position in the water column. In the
      past a passive orientation based on a buoy mechanism has been proposed for
      Euglena gracilis, but now it has been proven that this flagellate possesses a
      physiological gravireceptor and an active orientation. Numerous experiments in
      space using satellites, rockets and shuttles as well as in parabolic flights have
      been conducted as well as in functional weightlessness (simulated microgravity)
      on ground-based facilities such as clinostats to characterize the gravitaxis of
      Euglena. The threshold for gravity perception was determined and physiological,
      biochemical and molecular components of the signal transduction chain have been
      identified. In contrast to higher plants, some algae and ciliates, Euglena does
      not possess sedimenting statoliths to detect the direction of the gravity vector
      of the Earth. The gravireceptors were found to be mechano-sensitive Ca2+
      conducting ion channels thought to be located at the front end of the cell
      underneath the trailing flagellum. When activated by gravity-induced pressure due
      to sedimentation of the whole cell body, they allow a passive influx of calcium
      along a previously established ion gradient. The entering calcium binds to a
      specific calmodulin (CaM.2) which in turn activates an adenylyl cyclase producing
      cAMP from ATP. This cAMP is believed to activate a specific protein kinase A
      (PK.4), which is postulated to phosphorylate proteins inside the flagellum
      resulting in a bending and thus a course correction and reorientation with
      respect to the direction of the gravity vector. The elements of the signal
      transduction chain have been characterized by inhibitors and by RNAi to prove
      their involvement in gravitaxis.

PMID- 28429326
TI  - Wax Ester Fermentation and Its Application for Biofuel Production.
AB  - In Euglena cells under anaerobic conditions, paramylon, the storage
      polysaccharide, is promptly degraded and converted to wax esters. The wax esters
      synthesized are composed of saturated fatty acids and alcohols with chain lengths
      of 10-18, and the major constituents are myristic acid and myristyl alcohol.
      Since the anaerobic cells gain ATP through the conversion of paramylon to wax
      esters, the phenomenon is named "wax ester fermentation". The wax ester
      fermentation is quite unique in that the end products, i.e. wax esters, have
      relatively high molecular weights, are insoluble in water, and accumulate in the
      cells, in contrast to the common fermentation end products such as lactic acid
      and ethanol.A unique metabolic pathway involved in the wax ester fermentation is
      the mitochondrial fatty acid synthetic system. In this system, fatty acid are
      synthesized by the reversal of beta-oxidation with an exception that trans-2
      enoyl-CoA reductase functions instead of acyl-CoA dehydrogenase. Therefore,
      acetyl-CoA is directly used as a C2 donor in this fatty acid synthesis, and the
      conversion of acetyl-CoA to malonyl-CoA, which requires ATP, is not necessary.
      Consequently, the mitochondrial fatty acid synthetic system makes possible the
      net gain of ATP through the synthesis of wax esters from paramylon. In addition,
      acetyl-CoA is provided in the anaerobic cells from pyruvate by the action of a
      unique enzyme, oxygen sensitive pyruvate:NADP+ oxidoreductase, instead of the
      common pyruvate dehydrogenase multienzyme complex.Wax esters produced by
      anaerobic Euglena are promising biofuels because myristic acid (C14:0) in
      contrast to other algal produced fatty acids, such as palmitic acid (C16:0) and
      stearic acid (C18:0), has a low freezing point making it suitable as a drop-in
      jet fuel. To improve wax ester production, the molecular mechanisms by which wax
      ester fermentation is regulated in response to aerobic and anaerobic conditions
      have been gradually elucidated by identifying individual genes related to the wax
      ester fermentation metabolic pathway and by comprehensive gene/protein expression
      analysis. In addition, expression of the cyanobacterial Calvin cycle fructose-1,6
      bisphosphatase/sedohepturose-1,7-bisphosphatase, in Euglena provided
      photosynthesis resulting in increased paramylon accumulation enhancing wax ester
      production. This chapter will discuss the biochemistry of the wax ester
      fermentation, recent advances in our understanding of the regulation of the wax
      ester fermentation and genetic engineering approaches to increase production of
      wax esters for biofuels.

PMID- 28429327
TI  - Large-Scale Cultivation of Euglena.
AB  - From the middle of the twentieth century, microalgae have been exploited as a
      candidate biomass source of food and other products. One such candidate source is
      the fast-proliferating microalga Euglena gracilis. The commercial cultivation of
      E. gracilis began in 2007, after the success of its outdoor mass cultivation and
      improvement of the harvesting and drying methods suitable for Euglena cells. The
      commercialization of Euglena production is based on the strategy of "5Fs of
      Biomass," which refers to the development and production of commercial products
      including food, fiber, feed, fertilizer, and fuel from biomass." Although room
      for improvement remains in the productivity of Euglena biomass, the product with
      the highest value-food-is already profitable. By enhancing the productivity of
      its biomass, other Euglena products, including fiber, feed, fertilizer, and fuel,
      can be commercialized. Breeding and recombinant DNA technology studies are being
      conducted to accomplish more extensive application of Euglena. In addition, the
      search for a better place for outdoor mass cultivation of Euglena is ongoing.

PMID- 28429328
TI  - Ammonia production from amino acid-based biomass-like sources by engineered
      Escherichia coli.
AB  - The demand for ammonia is expected to increase in the future because of its
      importance in agriculture, industry, and hydrogen transportation. Although the
      Haber-Bosch process is known as an effective way to produce ammonia, the process
      is energy-intensive. Thus, an environmentally friendly ammonia production process
      is desired. In this study, we aimed to produce ammonia from amino acids and amino
      acid-based biomass-like resources by modifying the metabolism of Escherichia
      coli. By engineering metabolic flux to promote ammonia production using the
      overexpression of the ketoisovalerate decarboxylase gene (kivd), derived from
      Lactococcus lactis, ammonia production from amino acids was 351 mg/L (36.6%
      yield). Furthermore, we deleted the glnA gene, responsible for ammonia
      assimilation. Using yeast extract as the sole source of carbon and nitrogen, the
      resultant strain produced 458 mg/L of ammonia (47.8% yield) from an amino acid
      based biomass-like material. The ammonia production yields obtained are the
      highest reported to date. This study suggests that it will be possible to produce
      ammonia from waste biomass in an environmentally friendly process.

PMID- 28429329
TI  - Hydrogen production and microbial kinetics of Clostridium termitidis in mono
      culture and co-culture with Clostridium beijerinckii on cellulose.
AB  - Cellulose utilization by hydrogen producers remains an issue due to the low
      hydrogen yields reported and the pretreatment of cellulose prior to fermentation
      requires complex and expensive steps. Clostridium termitidis is able to breakdown
      cellulose into glucose and produce hydrogen. On the other hand, Clostridium
      beijerinckii is not able to degrade cellulose but is adept at hydrogen production
      from glucose; therefore, it was chosen to potentially enhance hydrogen production
      when co-cultured with C. termitidis on cellulose. In this study, batch
      fermentation tests were conducted to investigate the direct hydrogen production
      enhancement of mesophilic cellulolytic bacteria C. termitidis co-cultured with
      mesophilic hydrogen producer C. beijerinckii on cellulose at 2 g l-1 compared to
      C. termitidis mono-culture. Microbial kinetics parameters were determined by
      modeling in MATLAB. The achieved highest hydrogen yield was 1.92 mol hydrogen mol
      1 hexose equivalentadded in the co-culture compared to 1.45 mol hydrogen mol-1
      hexose equivalentadded in the mono-culture. The maximum hydrogen production rate
      of 26 ml d-1 was achieved in the co-culture. Co-culture exhibited an overall 32 %
      enhancement of hydrogen yield based on hexose equivalent added and 15 % more
      substrate utilization. The main metabolites were acetate, ethanol, lactate, and
      formate in the mono-culture, with also butyrate in the co-culture. Additionally,
      the hydrogen yield of C. beijerinckii only in glucose was 2.54 mol hydrogen mol-1
      hexose equivalent. This study has proved the viability of co-culture of C.
      termitidis with C. beijerinckii for hydrogen production directly from a complex
      substrate like cellulose under mesophilic conditions.

PMID- 28429330
TI  - Growth kinetics, fatty acid composition and metabolic activity changes of
      Crypthecodinium cohnii under different nitrogen source and concentration.
AB  - The effect of varying concentrations of the nitrogen source on the growth
      kinetics, lipid accumulation, lipid and DHA productivity, and fatty acid
      composition of C. cohnii was elucidated. Growth of C. cohnii was in three
      distinct growth stages: cell growth, lipid accumulation and a final lipid
      turnover stage. Most of lipids were accumulated in lipid accumulation stage (48
      120 h) though, slow growth rate was observed during this stage. NaNO3 supported
      significantly higher lipid content (26.9% of DCW), DHA content (0.99 g/L) and DHA
      yield (44.2 mg/g glucose) which were 2.5 to 3.3-folds higher than other N
      sources. The maximum level of C16-C18 content (% TFA) was calculated as 43, 54
      and 43% in lipid accumulation stage under low nitrogen (LN, 0.2 g/L), medium
      nitrogen (MN, 0.8 g/L) and high nitrogen (HN, 1.6 g/L) treatments, respectively.
      Cultures with LN, by down-regulating cell metabolism, trigger onset of lipogenic
      enzymes. Conversely, NAD+/NADP+-dependent isocitrate dehydrogenase (NAD+/NADP+
      ICDH) were less active in LN than HN treatments which resulted in retardation of
      Kreb's Cycle and thereby divert citrate into cytoplasm as substrate for ATP
      citrate lyase (ACL). Thereby, ACL and fatty acid synthase (FAS) were most active
      in lipid accumulation stage at LN treatments. Glucose-6-phosphate dehydrogenase
      (G6PDH) was more active than malic enzyme (ME) in lipid accumulation stage and
      showed higher activities in NaNO3 than other N-sources. This represents that
      G6PDH contributes more NADPH than ME in C. cohnii. However, G6PDH and ME together
      seems to play a dual role in offering NADPH for lipid biosynthesis. This concept
      of ME together with G6PD in offering NADPH for lipogenesis might be novel in this
      alga and needed to be explored.

PMID- 28429331
TI  - The correlation of CD19 + CD24 + CD38 + B cells and other clinicopathological
      variables with the proportion of circulating Tregs in breast cancer patients.
AB  - BACKGROUND: T regulatory cells (Tregs) are known to negatively control immune
      response. The frequency of these cells was inversely correlated with clinical
      outcomes of breast cancer. CD19+CD24hiCD38hi cells also play a critical role in
      inflammation and autoimmune disease. However, their function in tumor immune
      response is less studied. In this study we aimed to determine the role of
      CD19+CD24hiCD38hi cells and some other clinicopathological variables in
      increasing the proportion of Tregs in breast cancer patients. METHODS: We
      selected 47 patients with invasive ductal breast carcinoma and 50 healthy
      controls and obtained their blood samples. RESULTS: The proportion of circulating
      CD4+CD25+Foxp3+ Tregs and CD19+CD24hiCD38hi cells was significantly increased in
      breast cancer patients. We also found that increased proportion of Tregs in
      breast cancer is correlated with HER2 amplification, advanced clinical stages,
      serum TGF-beta1 and increased CD19+CD24hiCD38hi cells in the peripheral blood.
      CONCLUSION: Altogether, our data suggest that as much as Tregs, CD19+CD24hiCD38hi
      B cells could also have a part in the suppression of immune response in breast
      cancer.

PMID- 28429332
TI  - The effect of post-injection 18F-FDG PET scanning time on texture analysis of
      peripheral nerve sheath tumours in neurofibromatosis-1.
AB  - BACKGROUND: Texture features are being increasingly evaluated in 18F
      fluorodeoxyglucose positron emission tomography (18F-FDG PET) as adjunctive
      imaging biomarkers in a number of different cancers. Whilst studies have reported
      repeatability between scans, there have been no studies that have specifically
      investigated the effect that the time of acquisition post-injection of 18F-FDG
      has on texture features. The aim of this study was to investigate if texture
      features change between scans performed at different time points post-injection.
      RESULTS: Fifty-four patients (30 male, 24 female, mean age 35.1 years) with
      neurofibromatosis-1 and suspected malignant transformation of a neurofibroma
      underwent 18F-FDG PET/computed tomography (CT) scans at 101.5 +/- 15.0 and 251.7
      +/- 18.4 min post-injection of 350 MBq 18F-FDG to a standard clinical protocol.
      Following tumour segmentation on both early and late scans, first- (n = 37),
      second- (n = 25) and high-order (n = 31) statistical features, as well as fractal
      texture features (n = 6), were calculated and a comparison was made between the
      early and late scans for each feature. Of the 54 tumours, 30 were benign and 24
      malignant on histological analysis or on clinical follow-up for at least 5 years.
      Overall, 25/37 first-order, 9/25 second-order, 13/31 high-order and 3/6 fractal
      features changed significantly (p < 0.05) between early and late scans. The
      corresponding proportions for the 30 benign tumours alone were 22/37, 7/25, 8/31
      and 2/6 and for the 24 malignant tumours, 11/37, 6/25, 8/31 and 0/6,
      respectively. CONCLUSIONS: Several texture features change with time post
      injection of 18F-FDG. Thus, when comparing texture features in intra- and inter
      patient studies, it is essential that scans are obtained at a consistent time
      post-injection of 18F-FDG.

PMID- 28429333
TI  - Effect of Lactobacillus reuteri (DSM 17938) on methane production in patients
      affected by functional constipation: a retrospective study.
AB  - OBJECTIVE: Constipation is a common symptom affecting up to 30% of the Western
      population and is strongly associated with the presence of intestinal
      methanogens, which may directly inhibit motor activity. Two recent studies
      performed on adult and children affected by chronic constipation showed that the
      supplementation with L. reuteri significantly improved bowel movements. Whether
      its action is related to a decreasing of methane (CH4) production has never been
      tested. We have therefore designed a study aimed at testing this hypothesis.
      PATIENTS AND METHODS: Data of 20 adults (12 females, mean age 36.2 +/- 13.7)
      affected by functional constipation, treated with the probiotic L. reuteri (DSM
      17938) for 4 weeks who performed a H2/CH4 lactulose breath test (LBT) in our
      institution showing a CH4 production higher than 5 ppm were retrospectively
      analyzed from March to June 2015. Data recorded in their stool diary, reporting
      the frequency of defecations and stool consistency were also analysed, as well as
      the result of the LBT performed at the end of the treatment with L. reuteri.
      RESULTS: Four weeks of L. reuteri administration was associated with a
      significant decrease of mean CH4 production determined by LBT (from 20.8 +/- 15
      to 8.9 +/- 8.6; p < 0.0001 CI 95%) and of AUC value (from 5101.5 +/- 3571.13 to
      2128.4 +/- 2110.8; p < 0.0001 CI 95%). Moreover, a total disappearance of CH4
      production (< 5 ppm at LBT) was observed in 11 patients, while, we did not
      observe any significant decrease of H2 production (from 13.2 +/- 8.8 to 11.4 +/-
      7.3, CI 95%, n.s.). CONCLUSIONS: This study highlights for the first time the
      beneficial effect of Lactobacillus reuteri (DSM 17938) on chronic constipation,
      via a significant decrease of CH4 production.

PMID- 28429334
TI  - Thrombolysis of deep vein thrombosis and inhibiting chemotaxis of macrophage by
      MCP-1 blockage.
AB  - OBJECTIVE: Deep vein thrombosis (DVT) is one common vascular complication after
      trauma or surgery. Macrophage plays an important role in recanalization of
      thrombosis and monocyte chemotactic protein 1 (MCP-1) has a potent chemotactic
      role for macrophage. This study investigated the role of MCP-1 and macrophage in
      DVT thrombolysis. MATERIALS AND METHODS: DVT mice model was established for
      evaluating thrombosis grades, and divided into DVT, DVT + MCP-1 recombinant
      protein, and DVT + MCP-1 neutralizing antibody groups. MCP-1 mRNA and protein
      expression, weight/length ratio of thrombosis were tested at 1, 5, 9 and 15 day
      after DVT. F4/80 protein expression in thrombosis on day 9 was measured to
      reflect infiltration of macrophage. RESULTS: DVT model mice had thrombosis grade
      at 2.47 +/- 0.22 whilst no thrombosis occurred in sham group. DVT group had
      gradually increased MCP-1 mRNA and protein expression, which reached the peak at
      day 9, followed by decreased expression. Thrombosis weight/length ratio showed
      decreasing trends. MCP-1 protein injection significantly elevated MCP-1
      expression, decreased thrombosis weight/length ratio, and elevated macrophage
      infiltration. Injection of MCP-1 antibody remarkably decreased MCP-1 expression,
      elevated thrombosis weight/length ratio and macrophage infiltration. CONCLUSIONS:
      MCP-1 up-regulation participates in macrophage chemotaxis and thrombolysis after
      DVT formation. The blockade of MCP-1 weakens its thrombolysis effects.

PMID- 28429335
TI  - Imipenem-resistance in Serratia marcescens is mediated by plasmid expression of
      KPC-2.
AB  - OBJECTIVE: Imipenem is a broad-spectrum carbapenem antibiotic with applications
      against severe bacterial infections. Here, we describe the identification of
      imipenem-resistant Serratia marcescens in our hospital and the role of plasmid
      mediated KPC-2 expression in imipenem resistance. MATERIALS AND METHODS: We used
      the modified Hodge test to detect carbapenemase produced in imipenem-resistant
      strains. RESULTS: His resistance can be transferred to E. coli in co-culture
      tests, which implicates the plasmid in imipenem resistance. PCR amplification
      from the plasmid identified two products consistent with KPC-2 of 583 and 1050 bp
      that were also present in E. coli after co-culture. The restriction pattern for
      both plasmids was identical, supporting the transfer from the S. marcescens
      isolate to E. coli. Finally, gene sequencing confirmed KPC-2 in the plasmid.
      CONCLUSIONS: Due to the presence of KPC-2 in the imipenem-resistant S.
      marcescens, we propose that KPC-2 mediates antibiotic resistance in the S.
      marcescens isolate.

PMID- 28429336
TI  - Effects of a curcumin-based supplementation in asymptomatic subjects with low
      bone density: a preliminary 24-week supplement study.
AB  - OBJECTIVE: Osteopenia is a chronic bone condition characterized by decreased
      calcification, density, or bone mass that, if untreated, can lead to osteoporosis
      and bone fractures. Although its increasing prevalence, nowadays osteopenia is
      not adequately prevented and managed. In this study, we evaluated the efficacy,
      in term of changes in bone density, and safety of an oral formulation based on
      turmeric phytosome (Meriva(r)), in subjects suffering from low bone density.
      PATIENTS AND METHODS: 57 otherwise healthy subjects with low bone density were
      enrolled in this pilot, supplement study. Informed participants freely decided to
      follow either a standard management (SM) to control low bone density (control
      group=28) or SM associated with a curcumin-based oral supplementation (supplement
      group=29). The bone densities of heel, small finger and upper jaw were evaluated
      at inclusion and at different time points during the observational period (4, 12
      and 24 weeks), in all subjects. RESULTS: The bone density of the heel measured by
      the Sahara densitometer remarkably improved in the Meriva(r)-supplemented group,
      with a significant decrease of ultrasounds transmission values at week 12 (
      18.4%) and at week 24 (-21.0%), compared with baseline values. The bone densities
      of small finger and upper jaw also significantly increased during the study in
      supplemented subjects, reaching +7.1% and +4.8%, respectively, at week 24, with
      respect to values at inclusion. Noteworthy, no significant changes of heel, small
      finger and upper jaw densities were observed in the control group. Last, no
      safety and tolerability issues were reported during the observational period.
      CONCLUSIONS: This preliminary study suggests that a curcumin-based
      supplementation in combination with an appropriate lifestyle could be beneficial
      in the prevention and management of osteopenia.

PMID- 28429337
TI  - From acute to chronic pain: tapentadol in the progressive stages of this disease
      entity.
AB  - OBJECTIVE: Chronic pain is now recognized as a neural disease, which results from
      a maladaptive functional and structural transformation process occurring over
      time. In its chronic phase, pain is not just a symptom but also a disease entity.
      Therefore, pain must be properly addressed, as many patients still report
      unsatisfactory pain control despite on-going treatment. The selection of the
      therapy - taking into account the pathophysiological mechanisms of pain - and the
      right timing can result in a successful analgesic outcome. This review will
      present the functional and structural modifications leading to chronification of
      pain, focusing on the role of tapentadol in this setting. MATERIALS AND METHODS:
      For inclusion in this review, research studies were retrieved via a keyword-based
      query of multiple databases (MEDLINE, Embase, Cochrane). The search was last
      updated in November 2016; no limitations were applied. RESULTS: Functional and
      structural abnormalities of the nervous system associated with pain
      chronification have been reported in several conditions, including
      osteoarthritis, chronic back pain, chronic pelvic pain and fibromyalgia. Correct
      identification and treatment of pain in recurrent/progressive stage is crucial to
      prevent chronification and related changes in neural structures. Among analgesic
      drugs, tapentadol, with its dual mechanism of action (opioid agonist and
      noradrenaline reuptake blocker), has recently resulted active in pain control at
      both central and spinal level. CONCLUSIONS: Tapentadol represents a suitable
      candidate for patients at early progressive stage of pain who have developed
      neuroplasticity with modification of pain pathways. The availability of different
      doses of tapentadol may help clinicians to tailor treatment based on the
      individual need of each patient, with the aim to enhance therapeutic
      appropriateness in the treatment of musculoskeletal and neuropathic pain.

PMID- 28429338
TI  - Caffeic acid n-butyl ester-triggered necrosis-like cell death in lung cancer cell
      line A549 is prompted by ROS mediated alterations in mitochondrial membrane
      potential.
AB  - OBJECTIVE: The aim of the present study was to evaluate the anticancer activity
      of caffeic acid n-butyl ester against lung cancer cell line A549 and to
      investigate the underlying mechanism. MATERIALS AND METHODS: IC50 was determined
      by MTT assay. Fluorescent probes DCFH-DA, Indo 1/AM, DiOC6 were used to determine
      ROS, Ca2+, and mitochondrial membrane potential (DeltaPsim). ATP levels were
      determined by using ATP liteTM kit. DNA damage was investigated by DAPI and comet
      assays. Protein expression was investigated by Western blotting. RESULTS: Caffeic
      acid n-butyl ester exhibited lowest IC50 of 25 uM against lung A549 cell line.
      Caffeic acid n-butyl ester reduced the cell viability of A549 cells concentration
      and time-dependently. It also augmented the discharge of ROS and Ca2+ and
      lessened the mitochondrial membrane potential (DeltaPsim) and ATP levels in A549
      cells. Additionally, caffeic acid n-butyl ester also prompted DNA damage in A549
      cell line. Notably, caffeic acid n-butyl ester-stimulated the cytochrome c
      release only and exhibited no effect on the expression of apoptosis-related
      protein levels such as caspase-3, caspase-8, and Apaf-1. DISCUSSION: Caffeic acid
      n-butyl ester exhibited significant anticancer activity against lung cancer cell
      line A549. However, the anticancer activity was not due to apoptosis as no
      significant change was observed in the expression of apoptosis-related proteins.
      The anticancer activity of caffeic acid n-butyl ester may be attributed to
      necrosis-like cell death prompted by ROS-mediated alterations in DeltaPsim.
      CONCLUSIONS: Taken together, we conclude that caffeic acid n-butyl ester-induced
      A549 cells death displayed a cellular pattern characteristic of necrotic cell
      death and not of apoptosis.

PMID- 28429339
TI  - Observational multicentric study on chronic sciatic pain: clinical data from 44
      Italian centers.
AB  - OBJECTIVE: To provide information on the clinical presentation of sciatic
      neuropathy and its management in a real-world setting, and to analyze the effects
      of a multimodal approach based on the association of physical and pharmacological
      therapy. PATIENTS AND METHODS: A multicentric observational prospective study was
      conducted in 44 Italian tertiary centers specialized in Physical Medicine and
      Rehabilitation, Orthopedics, Neurology, Neurosurgery, and Rheumatology. To
      develop a shared management of LPB with sciatica, a dedicated clinical record was
      proposed to collect data about diagnosis, treatment, and outcomes. Pain,
      disability, and quality of life were recorded trough validated questionnaires at
      baseline and after a two-month follow-up. RESULTS: 394 patients (age, mean +/- SD
      55.7 +/- 14.1 years, 57.1% females) with chronic LBP and sciatica were enrolled
      in the study. The characteristics of the selected group showed a certain
      variability in the clinical presentation. At baseline, patients received several
      different therapeutic options among physical, pharmacological and neurotrophic
      treatments. A subgroup of 312 patients was treated with a combination of
      neurotrophic agents containing alpha-lipoic acid (ALA). After a two-month follow
      up, a general improvement in both perceived pain and functional disabilities was
      observed. A significant improvement (p < 0.001) in the Pain Numeric Rating Scale
      (NRS), Roland e Morris Disability Questionnaire (RMDQ) and Brief Pain Inventory
      (BPI) Italian short version was observed. CONCLUSIONS: Sciatic neuropathy is a
      multifaceted condition managed by means of a wide spectrum of therapeutic
      options. The results of this study suggest that a multimodal approach based on
      the association of ALA with physical and pharmacological therapies can be
      beneficial in the treatment of LBP with sciatica.

PMID- 28429340
TI  - Controlled, prospective, observational study on the efficiency and tolerability
      of a combination of potential Nrf2-inducing antioxidants and micronutrients as
      pre-treatment for ICSI in dyspermic patients with previous failure.
AB  - OBJECTIVE: To evaluate the efficiency of pre-treatment in dyspermic males in IVF
      couples with a combination of micronutrients, for the purpose of improving the
      fertilization rate, the implantation rate and the outcome of the pregnancy.
      PATIENTS AND METHODS: This controlled prospective clinical study was performed in
      two medically assisted reproduction centers. 59 males with mild oligo-astheno
      teratospermia (OAT) were admitted to the study. All of them had a history of
      previous in vitro fertilization (IVF) attempts with female partners aged < 40
      diagnosed having tubal or idiopathic infertility. The subjects upon enrolment
      underwent a semen test and afterward were treated with alpha lipoic acid and
      glutathione (Fertiplus SOD(r), Idi-Pharma, Catania, Italy) for 4 weeks (short
      term). The primary endpoints that were evaluated are the following: fertilization
      rate (mean fertilization), implantation rate and pregnancy rate. RESULTS: At the
      end of this study all the males (mean age 39.5 +/- 5.1) reported in not having
      any side effects during the administration of Fertiplus. Their female partners
      (mean age 34.9 +/- 4.5) underwent IVF using the ICSI technique. The number of
      oocytes retrieved and inseminated was not statistically different in comparison
      to previous attempts, but with the same number of oocytes treated, the
      fertilization rate per couple demonstrated statistically significant increase
      (p<0.001). We did not observe a percentage increase in evolutionary embryos, but
      we noticed an improvement in embryo quality per individual couple (p<0.001),
      associated with a net increase in the implantation rate per couple (p<0.001) in
      terms of clinical pregnancy. The estimated miscarriage risk after treatment was
      five times lower (p<0.001). CONCLUSIONS: Short-term treatment with micronutrients
      in dyspermic subjects can improve the reproductive outcome of the IVF procedure.

PMID- 28429341
TI  - HyalOne(r) in the treatment of symptomatic hip OA - data from the ANTIAGE
      register: seven years of observation.
AB  - OBJECTIVE: Several studies on knee osteoarthritis suggest that the intra
      articular administration of hyaluronic acid products may be a relevant option in
      the management of patients with persistent pain. The aim of this study is to
      report the data of efficacy of US-guided HyalOne(r)/Hyalubrix(r) 60 injections in
      a large population of patients with hip osteoarthritis, repeated at least 2 times
      per year for up to seven years. PATIENTS AND METHODS: This is a prospective, post
      marketing, cohort study. Data were collected from the ANTIAGE registry. Values of
      Lequesne index, pain VAS, NSAIDs intake, global medical and patients assessments
      were evaluated every six months from the baseline to the end of the follow-up,
      seven years later. The inclusion criteria were: age >=18 years, symptomatic hip
      osteoarthritis of at least 1-year duration, and up to 84 months of follow-up. All
      the patients received hyaluronic acid injections at least every six months, using
      ultrasound guidance to ensure accurate placement. RESULTS: 1022 patients were
      included in the study. The patients were categorized by age classes, gender, and
      body mass index (BMI). All the groups show a statistically significant reduction
      at all time points compared to baseline values of Lequesne index, pain VAS,
      NSAIDs intake, global medical and patients assessments. There are slight
      differences in the subgroups of overweighted, obese and over 70 years patients.
      CONCLUSIONS: Our study supports the clinical efficacy and safety of
      HyalOne(r)/Hyalubrix(r)60 in patients affected by osteoarthritis. This is the
      first study, reporting on a large cohort of patients in different categories with
      a long follow-up on seven years. The data confirm the proper use of ultrasound
      guided viscosupplementation (VS) as background therapy in the management of hip
      osteoarthritis.

PMID- 28429342
TI  - Assessment of serum endothelin-1 levels in rat appendicitis model and the effects
      of bosentan.
AB  - OBJECTIVE: In this study, the diagnostic value of serum endothelin-1 (ET-1)
      levels and the therapeutic effects of bosentan have been investigated in an
      experimental appendicitis rat model. MATERIALS AND METHODS: Twenty-one male
      Sprague-Dawley rats were chosen for the study. The rats were allocated into three
      groups as follows: Group 1 (control, n = 7), Group 2 (appendicitis, n = 7), and
      Group 3 (bosentan treatment, n = 7). At the 6th hour of the experiment, Groups 1
      and 2 received 2 ml saline, and group 3 received 30 mg/kg bosentan
      intraperitoneally. At the 24th postoperative hour, all rats were sacrificed and
      evaluated histopathologically to score the severity of appendicitis. The plasma
      malondialdehyde, reduced and total glutathione levels, serum, and appendiceal
      tissue ET-1 levels were evaluated. RESULTS: In this study, we found that the ET-1
      levels were significantly increased with appendicitis (p = 0.018). The
      administration of bosentan can statistically significantly both decrease the
      histopathologic injury in the inflamed appendix and increase the serum total
      glutathione levels (p = 0.002). CONCLUSIONS: The increase in plasma ET-1 levels
      may have a diagnostic value of acute appendicitis. We believe that manifestations
      that occur during the acute phase of appendicitis may be reduced with the
      administration of bosentan, which may also help prevent complications.

PMID- 28429343
TI  - Post-prandial effects of hazelnut-enriched high fat meal on LDL oxidative status,
      oxidative and inflammatory gene expression of healthy subjects: a randomized
      trial.
AB  - OBJECTIVE: Postprandial oxidative stress is characterized by an increased
      susceptibility of the organism towards oxidative damage after consumption of a
      meal rich in lipids and/or carbohydrates. Micronutrients modulate the immune
      system and exert a protective action by reducing low-density lipoproteins
      oxidation (ox-LDL) via induction of antioxidant enzymes. SUBJECTS AND METHODS:
      The clinical study was a randomized and cross-over trial, conducted through the
      CONSORT flowchart. We evaluated the gene expression of 103 genes related to
      oxidative stress (HOSp) and human inflammasome pathways (HIp), and ox-LDL level
      at fasting and after 40 g raw "Tonda Gentile delle Langhe" hazelnut consumption,
      in association with a McDonald's(r) Meal (McDM) in 22 healthy human volunteers.
      RESULTS: Ox-LDL levels significantly increased comparing no dietary treatment
      (NDT) vs. McDM, and decreased comparing McDM vs. McDM + H (p<0.05). Percentage of
      significant genes expressed after each dietary treatment were the follows: (A)
      NDT vs. McDM: 3.88% HIp and 17.48% HOSp; (B) NDT vs. McDM + H: 17.48% HIp and
      23.30% HOSp; (C) McDM vs. McDM + H: 17.48% HIp and 33.98% HOSp. CONCLUSIONS:
      Hazelnut consumption reduced post prandial risk factors of atherosclerosis, such
      as ox-LDL, and the expression of inflammation and oxidative stress related genes.
      Chronic studies on larger population are necessary before definitive conclusions.

PMID- 28429344
TI  - Up-regulation of microRNA-367 promotes liver steatosis through repressing TBL1 in
      obese mice.
AB  - OBJECTIVE: Increasing evidence has demonstrated that microRNAs (miRNAs) play a
      critical role in the progression of metabolic disorders, including obesity
      induced non-alcoholic fatty liver disease (NAFLD). In the present study, the
      expression and function of miR-367 were investigated. MATERIALS AND METHODS:
      C57BL/6 male mice aged 8 weeks were fed with a normal diet (ND) or high-fat-diet
      (HFD). The expression levels of miR-367 were analyzed in livers from two groups
      of mice by quantitative real-time PCR. Adenovirus containing miR-367 or negative
      control (NC) were constructed and administrated into C57BL/6 mice by tail vain
      injection. Potential targets of miR-367 were screened by miRWalk software and
      luciferase reporter assays. Mutagenesis analysis and Western blots were used to
      further determine the target of miR-367 in obese mice. RESULTS: We found that the
      expression of hepatic miR-367 was up-regulated in obese mice. In vitro and in
      vivo studies further demonstrated that overexpression of miR-367 mimics promoted
      triglyceride accumulation in cells and lean mice. At the molecular level,
      transducin beta-like 1 (TBL1), a coactivator of nuclear receptor peroxisome
      proliferator-activated receptor (PPAR) alpha, was identified as a direct target
      of miR-367. As a result, miR-367 overexpression resulted in an inhibition of
      fatty acid oxidation, leading to hepatosteatosis. CONCLUSIONS: Our data suggest
      miR-367/TBL1 regulatory pathway might have an important role for in the
      development of NAFLD.

PMID- 28429345
TI  - A peculiar case of diffuse hemangiomatosis of the left hepatic lobe in an
      asymptomatic adult patient: case report and literature review.
AB  - We report a rare case of diffuse hepatic hemangiomatosis (DHH) of the left
      hepatic lobe coexistent with giant hepatic hemangioma and without extra-hepatic
      involvement in an asymptomatic adult patient. Liver hemangiomas are the most
      common benign liver tumors. However, DHH without extra-hepatic involvement has
      rarely been reported in adults. Furthermore, giant hepatic hemangioma coexistent
      with DHH is even uncommon, although an association between hemangiomatosis and
      giant hepatic hemangiomas may be supposed. In this peculiar case, we observed an
      exclusive and widespread involvement of the left hepatic lobe with a sharp
      boundary between normal and altered liver parenchyma running along Cantlie's
      line.

PMID- 28429346
TI  - Dynamic and contrast enhanced CT imaging of lung carcinoma, pulmonary
      tuberculoma, and inflammatory pseudotumor.
AB  - OBJECTIVE: Our main aim was to investigate the effect of dynamic and contrast
      enhanced CT imaging on differential diagnosis of lung carcinoma, pulmonary
      tuberculoma, inflammatory pseudotumor, and coexisting pulmonary tuberculosis and
      lung cancer. PATIENTS AND METHODS: About, 144 patients with pulmonary sarcoidosis
      as the study subjects were chosen which included: 36 patients with lung
      carcinoma, 36 patients with pulmonary tuberculoma, 36 patients with inflammatory
      pseudotumor, 36 patients with coexisting pulmonary tuberculosis and lung cancer.
      CT imaging scan was carried out on all of these 144 patients. RESULTS: CT scan
      value of lung carcinoma was different from other conditions such as pulmonary
      tuberculoma, inflammatory pseudotumor, and coexisting pulmonary tuberculosis and
      lung cancer (p < 0.01). Similarly, the peak of enhancement of lung carcinoma was
      different from others including inflammatory pseudotumor, and coexisting
      pulmonary tuberculosis and lung cancer (p < 0.01). Both, the intensive added
      values and S/A values of lung carcinoma, inflammatory pseudotumor, and coexisting
      pulmonary tuberculosis and lung cancer differed between them (p < 0.01).
      CONCLUSIONS: Helical incremental dynamic CT is helpful in differential diagnoses
      of lung carcinoma, pulmonary tuberculoma, inflammatory pseudotumor, and
      coexisting pulmonary tuberculosis and lung cancer.

PMID- 28429347
TI  - SUMOylation in cardiac disorders - a review.
AB  - SUMOylation regulates diverse cellular processes including transcription, cell
      cycle, protein stability, and apoptosis. A recent research has now revealed the
      role of SUMO1 in cardiac disorders. Studies have evidenced that failing heart
      induces SUMO2/3 conjugation. Moreover, increased SUMO2/3- dependent modification
      has been observed to result in congestive heart disease such as cardiac
      hypertrophy by promoting cardiac cell death. Also, few recent studies have
      confirmed the role of SUMOylation in cardiac protein degradation. On the other
      hand, over-expression of SENP5, SUMO2/3-specific deconjugation enzyme has been
      observed to result in dilated cardiomyopathy or cardiac failure. So, the present
      review article would enlighten the latest updates about SUMOylation and
      associated factors during cardiac disorders.

PMID- 28429348
TI  - Diagnostic value of copeptin in acute myocardial infarction.
AB  - OBJECTIVE: The aim of this study was to investigate the effectiveness of copeptin
      in the early diagnosis of acute myocardial infarction (AMI), and to compare the
      diagnostic efficacy of copeptin with other cardiac markers. PATIENTS AND METHODS:
      A total of 160 cases were enrolled in the study. All were over 18 years of age,
      and consisted of 54 non-ST elevation MI (NSTEMI), 54 ST segment elevation MI
      (STEMI), and 52 healthy subjects (controls). Serum troponin-I, CK-MB mass,
      copeptin and CRP levels were measured in each of the cases, and were compared
      between the three groups for statistical differences. RESULTS: The copeptin
      levels in the STEMI (p < 0.001) and NSTEMI (p = 0.042) groups were found to be
      significantly higher than the control group. Spearman's correlation analysis
      showed a significant positive correlation between the level of copeptin and the
      presence of AMI (r = 0.285, p < 0.001), CK-MB mass (r = 0.246, p = 0.002), and
      troponin-I (r = 0.199, p = 0.012). Sensitivity, specificity, and AUC values of
      the tests, according to ROC analysis performed for the diagnosis of AMI were;
      troponin-I > 0.1 ng/mL (71.0%, 100.0%, and 0.855); CK-MB mass > 3.59 ng/mL
      (77.8%, 92.3%, and 0.911); CRP > 6.37 mg/L (53.7%, 88.5%, and 0.769); and
      copeptin > 2.47 ng/mL (66.7%, 75.0%, and 0.676), respectively (p < 0.001).
      CONCLUSIONS: Cardiac troponin remains the gold standard biomarker for the
      diagnostic evaluation of AMI. Copeptin can be used as a diagnostic marker in
      patients with suspected AMI in combination with other biomarkers, but, copeptin
      alone should not be considered as a single diagnostic marker in patients with
      suspected AMI.

PMID- 28429349
TI  - Association between the severity of newly diagnosed obstructive sleep apnea and
      subclinical carotid atherosclerosis in patients without overt cardiovascular
      disease.
AB  - OBJECTIVE: Obstructive Sleep Apnea (OSA) has been associated with both
      subclinical and accelerated atherosclerosis; however, it still remains unknown
      whether this association is unique or is mediated by the higher burden of co
      existing cardio-metabolic disorders frequently seen in patients with OSA.
      PATIENTS AND METHODS: A total of 40 subjects without clinically diagnosed
      cardiovascular disease (CVD) referred for polysomnography test were included in
      the study. Subjects with apnea/hypopnea index (AHI > 15/h) were classified as
      moderate/severe OSA. Subclinical changes in carotid atherosclerosis were assessed
      using mean carotid intima-media thickness (cIMT) and presence of atheromatic
      plaques on both carotid arteries. The measurement was performed using B-mode
      ultrasonogram. Framingham risk score was used in the approximation of
      cardiovascular risk. RESULTS: The mean age of our cohort was 56.8 years, 70% (n =
      28) of whom were males. Moderate/severe OSA was diagnosed in 21 subjects. Both
      groups were well matched in terms of clinical and demographic characteristics,
      and cardiovascular risk profile, as shown in their respective Framingham risk
      scores (10.4 +/- 6.6 vs. 11.8 +/- 8.8, p = NS). Patients with moderate/severe OSA
      had a higher mean AHI, 3% oxygen desaturation index, and lower minimum nocturnal
      oxygen saturation than controls. No significant differences were detected in
      terms of C-reactive protein levels. The two groups had similar cIMT (0.66 +/-
      0.17 vs. 0.75 +/- 0.20 p = 0.33) and presence of atheromatic plaque (50% vs. 45%,
      p = 1.00). CONCLUSIONS: Our study suggests that among patients with similar
      cardiovascular risk profile and free of overt CVD, the severity of newly
      diagnosed OSA was not correlated with increased inflammation or subclinical
      carotid atherosclerosis.

PMID- 28429350
TI  - The polymorphism of XRCC1 and coronary artery disease risk: a meta-analysis.
AB  - OBJECTIVE: Coronary artery disease (CAD) is a life-threatening disease and is
      caused by various factors, with genetic variation being an important risk factor.
      The association between X-ray repair cross-complementing group 1 (XRCC1)
      polymorphisms and CAD has been extensively studied with conflicting results. We
      performed a meta-analysis to investigate the overall association between XRCC1
      polymorphisms and CAD risk. MATERIALS AND METHODS: We searched PubMed and Embase
      databases until October 19, 2016. The total number and distribution of genotypes,
      genotyping methods, and ethnicity were extracted. Overall and subgroup analyses
      were performed. RESULTS: A total of seven publications involving 1.862 subjects
      and 1.568 controls were included in this meta-analysis. The Arg399Gln and
      Arg194Trp polymorphisms of XRCC1 were analyzed. The results indicated that the
      XRCC1 Arg399Gln homozygous GG genotype showed no association with CAD risk [GG
      vs. GA+AA: odd's ratio (OR) = 0.95, 95% confidence interval (CI) = 0.82-1.11, p =
      0.53] both in the overall and subgroups evaluation. However, the XRCC1 Arg194Trp
      homozygous TT genotype was associated with an increased CAD risk [(TT vs. TC+CC:
      OR =1.52, 95%CI = 1.16-2.00, p=0.003)]. Subgroup analysis based on ethnicity
      showed a significant increase in the association of CAD risk and the Arg194Trp
      gene polymorphism among the Asian population. CONCLUSIONS: This meta-analysis
      suggested that TT genotype in the Arg194Trp polymorphism contributes to the CAD
      susceptibility, particularly in the Asian population.

PMID- 28429351
TI  - TGFbeta1 protects myocardium from apoptosis and oxidative damage after ischemia
      reperfusion.
AB  - OBJECTIVE: Myocardial apoptosis is an important pathologic basis of ischemia
      reperfusion injury (I/R). Transforming growth factor beta1 (TGFbeta1)
      participates in the regulation of oxidative damage and apoptosis. TGFbeta1 is
      upregulated in the repair process of I/R injury. It is speculated that TGFbeta1
      over-expression is involved in the endogenous protective mechanism of I/R injury.
      This study explores the significance of TGFbeta1 in myocardial cell apoptosis
      after I/R. MATERIALS AND METHODS: Rat myocardial I/R injury model was
      established. Left ventricular ejection fraction (LVEF) and Left ventricular
      fractional shortening (LVFS) were detected by ultrasonic cardiogram. TGFbeta1
      expression in the myocardium was tested. H9C2 cells were cultured under ischemic
      hypoxic condition for 6 h, and then were treated by reoxygenation for 6 h to
      simulate I/R model. H9C2 cells were divided into three groups, including
      I/R+pIRES2-Blank, I/R+pIRES2 TGFbeta1, and I/R+pIRES2-TGFbeta1+LY364947. TGFbeta1
      mRNA and protein levels were evaluated. Cell apoptosis and reactive oxygen
      species (ROS) were determined by flow cytometry. RESULTS: LVEF and LVFS
      significantly decreased in I/R group compared with Sham group. TGFbeta1 mRNA and
      protein expressions in myocardium from I/R group up-regulated than the control.
      I/R treatment markedly elevated TGFbeta1 mRNA and protein levels, increased ROS
      content, and enhanced cell apoptosis in H9C2 cells. Over-expression of TGFbeta1
      significantly weakened ROS production and apoptosis in H9C2 cells after I/R.
      TGFbeta receptor inhibitor LY364947 restrained ROS production and apoptosis
      attenuation in H9C2 cells treated by TGFbeta. CONCLUSIONS: TGFbeta1 alleviates
      myocardial cell apoptosis after I/R. Blocking TGFbeta1 attenuates the protective
      effect of TGFbeta1 on I/R injury.

PMID- 28429352
TI  - Difference in resting-state fractional amplitude of low-frequency fluctuation
      between bipolar depression and unipolar depression patients.
AB  - OBJECTIVE: To investigate the difference in fractional amplitude of low-frequency
      fluctuation (fALFF) of localized brain activities in the resting-state between
      bipolar depression and unipolar depression patients and to find biological
      markers that differentiate the two groups of patients. PATIENTS AND METHODS:
      Thirteen patients with bipolar depression, 15 patients with unipolar depression,
      and 16 healthy control subjects that were matched in age and years of education
      were subjected to 3.0 T resting-state functional magnetic resonance scans. The
      values of whole brain fALFF were calculated and statistical analysis was
      performed. RESULTS: The fALFF-values of the right inferior temporal gyrus, left
      cerebellar posterior lobe, right middle temporal gyrus, left inferior frontal
      gyrus/insula, right inferior frontal gyrus/insula, left lingual gyrus and right
      middle temporal gyrus of the three groups showed significant differences (p <
      0.05). Compared with the healthy control (HC) group, the fALFF-values of the
      unipolar depression (UD) patient group significantly increased in the right
      superior temporal gyrus, left insula, left inferior frontal gyrus, right inferior
      frontal gyrus, right supramarginal gyrus and right medial frontal gyrus but
      significantly decreased in the right medial occipital gyrus, left frontal lobe,
      right superior parietal lobule; the fALFF-values of the bipolar depression (BD)
      patient group significantly decreased in the left cerebellum posterior lobe,
      right lingual gyrus, left lingual gyrus, right middle temporal gyrus, left middle
      temporal gyrus, and left superior frontal gyrus and significantly increased in
      the right inferior frontal gyrus and left insula compared to those of the HC
      group; compared with those of the UD group, the fALFF-values of the BD group
      significantly decreased in the left middle occipital gyrus, right middle temporal
      gyrus, left middle frontal gyrus, and left medial frontal gyrus. CONCLUSIONS: The
      brain activities of BD and UD patients in the resting-state exhibit
      abnormalities, which differ between the two groups of patients.

PMID- 28429353
TI  - Roles of the Nrf2/HO-1 pathway in the anti-oxidative stress response to ischemia
      reperfusion brain injury in rats.
AB  - OBJECTIVE: The aim of this study was to investigate the roles of the Nrf2/HO-1
      pathway in the responses to the oxidative stress created by ischemia-reperfusion
      brain injury in rats. MATERIALS AND METHODS: 54 healthy, adult, male SD rats were
      included in the study. Eighteen (18) rats were placed in the sham group. The
      ischemia-reperfusion model was created in the other 36 rats, among which 18
      received injections of Nrf2 agonist before the surgery. The suture method was
      used to create artery occlusions in the right brain of the rats; and reperfusion
      was done after 90-minute ischemia (MCAO); while no suture was inserted in the
      sham group. At 3, 6, 12, 24, 48 and 72 hours after the modeling, their
      neurological functions were evaluated. Also, at different time points, rats were
      decapitated, and their fresh brain tissues were used to detect the infarct volume
      percentages by TTC staining and the brain water contents by the dry-wet weight
      method. The SOD contents in the brain tissue were measured by Xanthine oxidase
      assay. RT-PCR was used to detect the mRNA expression of HO-1 in the brain
      tissues, and western blot method was used to detect the expression level of HO-1
      and Nrf-2. RESULTS: The rats in the sham group had no obvious neurological
      defects; while those in the MCAO group showed significant neurological defects at
      all time points. The MCAO group had higher neurological evaluation scores than
      the sham group. TTC staining showed that infarct in the MCAO group kept
      increasing over time and peaked at 24h. Measurements of SOD found that the sham
      group had the highest SOD among the three groups, and showed no significant
      fluctuation over time. The MCAO group had much lower SOD activities than the sham
      group at all the time points. The higher the level of HO-1mRNA and protein
      expression in the brain tissue of rats in each group, the higher the degree of
      brain injury, but the lower the level of Nrf2 protein expression and the lower
      degree of brain injury. Nrf2 agonist markedly improved all these indicators in
      the rats which underwent the MCAO surgery. CONCLUSIONS: The expression of HO-1
      after ischemia-reperfusion brain injury may contribute to the increased infarct
      volume. Activation of Nrf2 could improve the prognosis of ischemia-reperfusion
      brain injury.

PMID- 28429354
TI  - The role of the hippocampus and the function of calcitonin gene-related peptide
      in the mechanism of traumatic brain injury accelerating fracture-healing.
AB  - OBJECTIVE: This research attempts to identify the part the hippocampus plays in
      accelerated fracture-healing after traumatic brain injury as well as to test
      functions of calcitonin gene-related peptide (CGRP) during this process.
      MATERIALS AND METHODS: Experiments were carried out on Male Sprague-Dawley rats
      that were split into four groups at random: TBI-fracture group, fracture-only
      group, TBI-only group, and control group. In the first week, blood specimen would
      be drawn from rats among the groups except those of the control group at three
      time points (24, 72 and 168 hours) post-damage. These rats would be assessed from
      the neurological perspective based on their grades of performance in a sequence
      of tests 24 hours before and 12 hours after brain injury. Blood samples were also
      taken from the control group 24 hours before the injury, and whole brain tissues
      in the injured groups were harvested at 72 and 168 hours post-injury. We compared
      the serum CGRP concentration, the distribution of CGRP, the CGRP expression, and
      the expression of CGRP in the hippocampus, the expression of CGRP in the
      hippocampus, the expression of CGRP in the hippocampus, and the expression of
      CGRP in the brain by immunohistochemistry, Western blotting, RT- Of CGRP RNA
      expression levels. RESULTS: Neurological examinations suggested that the
      functions of the cerebral cortex, cerebellum, and brain stem showed significant
      differences pre- and post-injury (p < 0.001). ELISA analysis indicated a great
      density of CGRP in TBI-fracture group at different time points. Furthermore, in
      the TBI-fracture group, CGRP in both hippocampus and the whole brain showed a
      noticeable augment in RT-PCR and western blot analysis at 72 and 168 h post
      injury, and only in this group, immunohistochemistry analysis indicated that CGRP
      was present in the hippocampus at 168 hours post-injury. CONCLUSIONS: We observed
      that the hippocampus and CGRP were responsible for quick bone-healing mechanisms.
      We suggest a role for the hippocampus in accelerated fracture healing. CGRP
      expression, as determined by IHC, cannot be observed in other groups, indicating
      that the hippocampus may be the specific component of the brain that responds to
      "big stress".

PMID- 28429355
TI  - Lewy pathological study on alpha-synuclein in gastrointestinal tissues of
      prodromal Parkinson's disease.
AB  - OBJECTIVE: In the gastrointestinal neural system, the emergence of Lewy Body (LB)
      is usually earlier than the clinical diagnosis of Parkinson (PD) motor symptoms.
      Therefore, this study is aimed to explore whether the LB in the gastrointestinal
      tract of prodromal PD patients. PATIENTS AND METHODS: 98 paraffin embedded tissue
      specimens from 57 PD patients were collected in the Second Affiliated Hospital of
      Soochow University archives, as well as 98 tissue specimens of 90 non-PD patients
      undergone surgical resection. The pathological sections were stained by the
      immune-histochemistry method. The positive staining of aggregated a-Synuclein (a
      a-syn) and phosphorylated a-Synuclein (p-a-syn) in gastrointestinal tract were
      counted to analyze the distribution of the expression of a/p-a-syn in the
      prodromal PD patients before diagnosis (0-5 years, 6-10 years, 11-20 years).
      RESULTS: According to results from the immunohistochemical staining of a/p-alpha
      syn, 35 (52.23%) and 30 (44.78%) tissue blocks were positively stained
      respectively in total 67 tissue blocks provided from 39 prodromal PD patients.
      And there were 46 (46.94%) and 25 (25.51%) positive staining in 98 tissue blocks
      from the control group. In 31 tissue blocks collected from 18 PD patients, there
      were 19 (61.29%) and 15 (48.39%) tissue blocks with the a/p-a-syn positive
      staining. Compared with non-PD patients from the control group, the a-a-syn
      positive rate was not significantly increased in the pre- and post-diagnosis PD
      patients (p>0.05). However, p-a-syn of both groups increased significantly
      (p<0.05). Also, the positive expression rate of a/p-a-syn in the 6-10-year group
      was lower than that in the 0-5-year and 11-20-year, and the positive rate of the
      0-5-year group was the highest (p<0.05). CONCLUSIONS: p-a-syn as the main
      component of Lewy body of nervous system in the gastrointestinal track may be
      used as a characteristic predictive marker of PD and the prevention of PD
      disease.

PMID- 28429356
TI  - Thrombolysis in acute stroke without angiographically documented occlusion.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of intra
      arterial thrombolysis (IAT) using urokinase (UK) in acute stroke patients without
      angiographically-documented occlusion, and to define predictors of clinical
      outcome. PATIENTS AND METHODS: We analyzed clinical and radiological data of
      acute ischemic stroke patients whose angiography did not show an arterial
      occlusion within six hours of symptom onset and who were further treated with IAT
      using UK. The primary outcome was a modified Rankin Scale (mRS) score <= 2 at 90
      days' post procedure. RESULTS: In a thrombolysis database of 263 patients, we
      identified 51 patients without angiographically-documented arterial occlusion who
      received IAT with UK within six hours of symptom onset. The median baseline NIH
      stroke scale measurement was 11 (range: 8-20). From symptom onset, the mean time
      to treatment was 4.1 +/- 1.3 h (median: 4.5 h; range: 1.5-6.0 h). Immediate and
      dramatically clinical improvement was seen in 29/51 (56.9%) patients. One patient
      (2.0%) developed a symptomatic intracranial hemorrhage. At three months, 38/51
      (74.5%) patients were independent (mRS <=2), 13/51 (25.5%) patients were
      dependent (mRS > 3), and no patients died. No predictors of clinical outcome were
      identified. CONCLUSIONS: IAT using UK can be a safe and efficacious therapy for
      the treatment of acute ischemic stroke in patients without angiographic
      occlusion. Approximately 75% of these patients had a favorable clinical outcome
      and thrombolysis-related symptomatic hemorrhage was low.

PMID- 28429357
TI  - Inhibition of pulmonary carcinoma proliferation or metastasis of miR-218 via down
      regulating CDCP1 expression.
AB  - OBJECTIVE: Pulmonary carcinoma is one common malignant tumor with a high risk of
      recurrence and metastasis. Non-small cell lung cancer (NSCLC) is the most common
      subtype. As one tumor biomarker, microRNA (miR) has tissue sensitivity and can
      facilitate oncogene or inhibit tumor suppressor gene. MiR-218 has abnormal
      expression and can work as one molecular marker for tumors. However, its
      expression and function mechanism in lung cancer cells have not been fully
      illustrated. MATERIALS AND METHODS: In vitro cultured pulmonary adenoma A549
      cells and normal bronchial epithelial cell line 16HBE were tested for miR-218
      expression. A549 cells were transfected with miR-218 mimic or negative controls,
      followed by real-time PCR quantifying for miR-218. MTT method was used to test
      cell proliferation, whilst Transwell chamber was adopted for measuring cell
      invasion. Dual luciferase reporter gene assay (DLRGA) was used to test target
      relationship between miR-218 and CDCP1. Western blot was used to test CDCP1
      expression. RESULTS: MiR-218 was down-regulated in A549 cells compared to 16HBE
      (p<0.05). Transfection of miR-218 mimic significantly facilitated miR-218
      expression, inhibited tumor proliferation or invasion. As the target gene of miR
      218, CDCP1 expression was suppressed by miR-218 over-expression (p<0.05 compared
      to control group). CONCLUSIONS: MiR-218 inhibits NSCLC proliferation or
      metastasis via down-regulating CDCP1, and can work as one novel molecular target
      for lung cancer diagnosis.

PMID- 28429358
TI  - SLPI promotes the gastric cancer growth and metastasis by regulating the
      expression of P53, Bcl-2 and Caspase-8.
AB  - OBJECTIVE: The incidence of gastric cancer is very high all over the world, but
      the mechanism of the occurrence and development of gastric cancer is unclear.
      Secretory leukocyte protease inhibitor (SLPI) is overexpressed in gastric, lung
      and ovarian cancers, which accelerates the metastasis of cancer cells. In this
      research, we mainly explored the expression level and possible mechanism of SLPI
      in gastric cancer. PATIENTS AND METHODS: The expression and clinical significance
      of SLPI in 68 cases of gastric cancer tissues and adjacent tissues were detected
      by qRT-PCR. Cell Counting Kit-8 (CCK8) assay was used to detect the proliferation
      ability of gastric cancer cell lines. In addition, we used Western blot to
      clarify the relationship between SLPI and metastasis. RESULTS: Compared with the
      adjacent tissues, we found that SLPI was highly expressed in gastric cancer
      tissues. We also found that the expression of SLPI was in significant correlation
      with the survival time, clinical classification and size of the tumor. What's
      more, SLPI could promote the proliferation and metastasis of gastric cancer by
      regulating P53, Bcl-2 and Caspase-8 expression through apoptosis signaling
      pathway. CONCLUSIONS: We concluded that SLPI was closely related with to invasion
      and metastasis of gastric cancer. Perhaps we can hopefully find new targets for
      the treatment of gastric cancer.

PMID- 28429360
TI  - Effects of silencing annexin A5 on proliferation and invasion of human
      cholangiocarcinoma cell line.
AB  - OBJECTIVE: We investigated the expression of annexin A5 (ANXA5) in human
      cholangiocarcinoma (CCA) cell line and its effect on proliferation, migration,
      and apoptosis of human CCA cells. MATERIALS AND METHODS: Expression of ANXA5 was
      detected by fluorescent quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) and western blotting method in 2 human CCA cell lines, QBC939
      and RBE. 3 shRNA plasmids for ANXA5 silencing (ANXA5-sh1, ANXA5-sh2, ANXA5-sh3)
      and 1 negative control plasmid were constructed to infect QBC939 cells. The
      infection efficiency, expression of ANXA5, apoptosis and cell cycle of QBC939
      cell were measured separately. RESULTS: The expression of ANXA5 in QBC939 cell
      was significantly higher than RBE cell. Expressed ANXA5 protein in the QBC939-KD
      cell (QBC939 cell treated by RNAi) was significantly lower than QBC939-BC (QBC939
      cell) and QBC939-NC cells (QBC939 cell treated by scramble plasmid). The ratio of
      G0/1 phase cells and apoptosis rate increased in QBC939-KD cell. The
      proliferation activity and invasion ability decreased in QBC939-KD cell compared
      with QBC939-NC and QBC939-BC cells. CONCLUSIONS: ANXA5 play important role in the
      migration and apoptosis of CCA cells. Inhibiting the expression of ANXA5
      significantly reduce the proliferation, migration and invasion ability of QBC939
      cells, and increase the apoptosis of QBC939 cells.

PMID- 28429359
TI  - The role of angiogenesis inhibitors re-challenge in colorectal cancer previously
      treated with bevacizumab: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The potential usefulness of angiogenesis inhibitors (AIs) re-challenge
      in the treatment of metastatic colorectal cancer (CRC) who previously treated
      with bevacizumab has not been established yet. MATERIALS AND METHODS: We
      identified relevant clinical studies through searching databases up to October
      2016. Prospective clinical trials investigating AIs re-challenge in metastatic
      CRC were included for analysis. The primary endpoint was overall survival with
      secondary endpoint progression-free survival. Estimates of treatment effect from
      individual trials were combined using standard techniques. RESULTS: A total of
      2.686 patients with metastatic CRC who previously received bevacizumab were
      identified for analysis. The meta-analysis results demonstrated that AI re
      challenge significantly improved progression-free survival (hazard ratio: 0.63,
      95% confidence interval: 0.52-0.76, p < 0.001) and overall survival (hazard
      ratio: 0.82, 95% confidence interval: 0.76-0.89, p < 0.001) when compared to non
      AI containing regimens. No publication bias was detected by Begg's and Egger's
      tests for PFS (p = 0.09 and p = 0.32) and OS (p = 0.85 and p = 0.50).
      CONCLUSIONS: Our pooled analysis shows that AIs re-challenge offers an improved
      PFS and OS in the treatment of metastatic CRC patients who relapsed after a first
      line bevacizumab-containing therapy. Further prospective clinical trials are
      still needed to confirm our findings.

PMID- 28429361
TI  - Pathologic character and diagnosis of female primary genital system diffuse large
      B cell lymphoma.
AB  - OBJECTIVE: We investigated the clinicopathological characteristics and
      immunophenotype of female genital system diffuse large B-cell lymphoma (DLBCL) in
      order to improve diagnosis and therapy efficacy. PATIENTS AND METHODS: The
      clinicopathologic features of 13 cases with primary DLBCL of the female genital
      system were studied retrospectively. According to the immunophenotypes, 10 cases
      were classified as germinal center B-cell-like DLBCL and the other 3 as non
      center B-cell-like DLBCL. RESULTS: The immunohistochemistry data showed that
      CD20, PAX-5, and CD79a tested positive, while CD3, CD43 and CD45RO tested
      negative in all 13 cases. In 7 cases EMA was positive, in 9 cases CD10 was
      positive, in 11 cases bcl-6 was positive, and in 9 cases MUM-1 was tested
      positive. In one case, the Ki-67 index was less than 59%, in 3 cases Ki-67 index
      was between 60% to 89% and it was more than 90% in the remaining 9 cases (the
      median was 90%). All 13 patients underwent hysterectomy, while in 10 of them
      hysterectomy was followed by chemotherapy. The survival time was 3 to 20 months.
      CONCLUSIONS: Primary diffuse large B-cell lymphoma of the primary female genital
      system is a rare and highly invasive condition that can be easily misdiagnosed. A
      complete diagnosis is very important because the treatment and prognosis vary in
      different histological types. Moreover, the immunohistochemistry is an useful
      diagnostic method for this type of cancer.

PMID- 28429362
TI  - Wnt11 overexpression promote adipose-derived stem cells differentiating to the
      nucleus pulposus-like phenotype.
AB  - OBJECTIVE: Our present study aimed to evaluate the effects of Wnt11
      overexpression on the adipose-derived stem (ADSCs) cells differentiation to the
      nucleus pulposus (NP) cells and its function in the ADSCs cells growth,
      proliferation and induction of the NP cells markers. MATERIALS AND METHODS: The
      cell growth was detected using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide) (MTT) assay and the cell cycle was assessed by the flow
      cytometry. The cells morphology was evaluated using the transmission electron
      microscopy. The transfection efficiencies of Wnt11 lentivirus were observed under
      fluorescence microscope. Besides, Quantitative Real-time PCR and Western blot
      analysis were applied to detect the relative mRNA and protein levels. RESULTS:
      Wnt11 lentivirus treatment could inhibit the ADSCs cells growth and arrest the
      cell cycle progression at the G0/G1 phase. Besides, the overexpression of Wnt11in
      ADSCs cells could induce the expression of the NP cells markers. Levels of SOX-9,
      aggrecan, and collagen type II were significantly increased in the ADSCs cells
      transfected with the Wnt11 lentivirus, in comparison with the untreated cells or
      the vector controls. CONCLUSIONS: The Wnt11 overexpression may provide some
      experimental evidence for the possible opportunity of the Wnt11 to promote the
      ADSCs cells differentiating to the NP cells. Therefore, the Wnt11 overexpression
      may have a potential utility for the treatment of the intervertebral disc
      degeneration.

PMID- 28429363
TI  - Two unilateral puncturation comparative analyses of multiple-level fresh
      osteoporotic vertebral body compression fractures treated with percutaneous
      vertebroplasty guided by C-arm fluoroscopy or in senile patients.
AB  - OBJECTIVE: To compare the curative effects of two unilateral puncturation
      percutaneous vertebroplasty (PVP) for the pain caused by multiple-level
      osteoporotic vertebral body compression fractures (OVCF) in senile patients.
      PATIENTS AND METHODS: From June 2008 to November 2014, eighty-nine cases
      suffering from fresh multiple-level OVCF were randomly divided into experimental
      group (n=51) and control group (n=38). Patients underwent PVP guided by C-arm
      fluoroscopy in the prone position. We monitored and recorded the visual analgesic
      scale (VAS) at pre-operation and 2 days post-operation, operation time, exposure
      duration, bone cement injection amount and extraosseous cement leakages. RESULTS:
      PVP procedures were successful in both groups without serious complications. The
      VAS scores in both two groups at 2 days post-operation were significantly lower
      than VAS scores at pre-operation (p<0.05). The operation time and exposure
      duration in the observational group were significantly lower than those in the
      control group (p<0.05). However, bone cement injection amount and extraosseous
      cement leakages in the observing group were similar to those in control (p>0.05).
      CONCLUSIONS: The curative effects of two unilateral puncturation PVPs were
      satisfactory. However, puncturation method had lower operation time and lower X
      ray exposure dose. We concluded that puncturation method was a suitable method to
      be considered for clinical application.

PMID- 28429364
TI  - Application of gene detection technique in the antenatal diagnosis of hereditary
      hearing loss.
AB  - OBJECTIVE: Gene chip and gene sequencing techniques were used to detect the main
      pathogenic genes in pregnant women with hereditary hearing loss. PATIENTS AND
      METHODS: From May 2015 to May 2016, 1080 pregnant in Xuzhou Maternal and Child
      Health Hospital were enrolled in this study. Women age range was 18 to 40 years.
      4 genes and 9 mutation sites, including 4 sites (35delG, 176, 235delC and 299) in
      GJB2 gene, 2 sites (2168A>G and IVS-7-2A>G) in SLC26A4 (PDS) gene, 2 sites
      (1494C>T and 1555A>G) in 12s rRNA gene and 1 site (538C>T) in GJB3 gene, were
      detected using the GeeDom(r) 9-item hereditary hearing loss gene detection kit.
      Deafness genes in the husband of the pregnant woman with GJB2 and SLC26A4
      positive gene mutations were verified using Sanger sequencing. Fetuses with the
      same deafness genes as their parents were diagnosed before delivery using
      amniocentesis. RESULTS: 48 patients (4.45 %) were detected positive for
      hereditary hearing loss. Most of them (28 cases) were identified with GJB2 gene
      mutation (1 case with 176 site mutation, 22 cases with 235delC site mutation and
      5 cases with 299 site mutation). We had 15 cases of the SLC26A4 gene mutation (3
      cases of 2168A>G site mutation and 12 cases of IVS-7-2A>G site mutation), 2 cases
      of 538C>T site mutation of GJB3 gene and 3 cases of 1555A>G site mutation of 12s
      rRNA gene. CONCLUSIONS: The gene detection technique has a great health-economic
      significance in screening the main pathogenic genes involved in the hereditary
      hearing loss.

PMID- 28429365
TI  - A randomized clinical trial about presence of pathogenic microflora and risk of
      peri-implantitis: comparison of two different types of implant-abutment
      connections.
AB  - OBJECTIVE: The aim of this in vivo study was to evaluate two different types of
      implant-abutment connections: screwed connection and cemented connection,
      analyzing peri-implant bacteria microflora as well as other clinical parameters.
      PATIENTS AND METHODS: Twenty implants were selected, inserted in 20 patients, 10
      with a screwed implant-abutment connection (Group 1) and 10 with a cemented
      implant-abutment connection (Group 2). The peri-implant microflora was collected,
      after at least 360 days from the prosthetic rehabilitation, using paper points
      inserted in peri-implant sulcus for 30 s. Polymerase chain reaction (PCR) Real
      time analyzed the presence of 9 bacteria periodontal-pathogens and Candida
      albicans. RESULTS: Our findings showed that bacteria colonized all Groups
      analyzed, the average bacterial count was 3.7 E +08 (+/-1.19) in Group 1,
      compared to 2.1 E +08 (+/-0.16) in Group 2; no statistically significant
      differences were observed (p>0.0.5). In Group 1, however, bacterial colonization
      of peri-implant sulci was over the pathogenic threshold for 5 bacteria,
      indicating a high-risk of peri-implantitis. Also in Group 2, results showed a
      microflora composed by all bacteria analyzed but, in this case, bacterial
      colonization of peri-implant sulci was over the pathogenic threshold for only 1
      bacterium, indicating a lower risk of peri-implantitis. Moreover, clinical
      parameters (PPD > 3 mm and m SBI > 0) confirmed a greater risk of peri
      implantitis in Group 1 compared to Group 2 (p<0.05). CONCLUSIONS: We concluded
      that, also after only 360 days, implants with screwed connection showed a higher
      risk of peri-implantitis that implants with cemented connection.

PMID- 28429366
TI  - Analysis of transcriptional activities of angiogenic biomarkers during
      intrauterine complications leading to preterm birth.
AB  - OBJECTIVE: Pre-eclampsia, growth retardation and preterm delivery are the most
      common reasons leading to increased maternal and perinatal mortality. The
      increased expression of hypoxia induced factors, such as HIF-1, triggers the
      overexpression of anti-angiogenic genes. The aim of this study was to determine
      the transcriptional activity of individual pro- and anti-angiogenic markers
      (VEGF, HIF-1, sEng, Flt-1, PlGF-1) in maternal blood samples from patients with
      spontaneous preterm labor, preterm labor in combination with pre-eclampsia and
      fetal growth restriction in comparison with physiologically terminated
      pregnancies. PATIENTS AND METHODS: The transcriptional activity of specific genes
      was detected from the blood of patients using the chromatin immunoprecipitation
      capture method coupled with quantitative real-time PCR. RESULTS: The maximum
      differences in mRNA levels of PlGF-1 and VEGF-A were detected in two groups: the
      group of normal-term birth with complications and the group of preterm labor with
      complications (both significantly lower than the control, p < 0.001). In
      contrast, a marked increase of mRNA levels was found in the same groups of
      patients for the HIF-1, endoglin and Flt-1 genes (p < 0.001). CONCLUSIONS:
      According to our results, we can conclude that increased oxidative stress,
      increasing the expression levels of anti-angiogenic genes and reduction of the
      transcriptional activity of pro-angiogenic genes can provide additional
      information during diagnostics of pathological complications of labor.

PMID- 28429367
TI  - Can Type 1 diabetes progression be halted? Possible role of high dose vitamin D
      and omega 3 fatty acids.
AB  - In Type 1 Diabetes (T1D) in children, close to the onset the requirements of
      insulin are often reduced. This represents a transient recovery of endogenous
      insulin secretion named "honeymoon" because transient and followed by a
      progressive decline in C-peptide secretion. This case report describes the effect
      of administration of high dose vitamin D and Omega-3 fatty acids on T1D
      progression in a 8-year-old child. At today after one year and a half from the
      onset of T1D, the subject shows a near-normal blood glucose with the
      administration of 1.5-2 UI of insulin once a day. Thus this report may be of
      assistance to design additional studies to determine and validate the effect of
      administration of vitamin D and Omega-3 fatty acids on the progression of T1D.

PMID- 28429368
TI  - ARALAR/AGC1 deficiency, a neurodevelopmental disorder with severe impairment of
      neuronal mitochondrial respiration, does not produce a primary increase in brain
      lactate.
AB  - ARALAR/AGC1 (aspartate-glutamate mitochondrial carrier 1) is an important
      component of the NADH malate-aspartate shuttle (MAS). AGC1-deficiency is a rare
      disease causing global cerebral hypomyelination, developmental arrest, hypotonia,
      and epilepsy (OMIM ID #612949); the aralar-KO mouse recapitulates the major
      findings in humans. This study was aimed at understanding the impact of ARALAR
      deficiency in brain lactate levels as a biomarker. We report that lactate was
      equally abundant in wild-type and aralar-KO mouse brain in vivo at postnatal day
      17. We find that lactate production upon mitochondrial blockade depends on up
      regulation of lactate formation in astrocytes rather than in neurons. However,
      ARALAR-deficiency decreased cell respiration in neurons, not astrocytes, which
      maintained unchanged respiration and lactate production. As the primary site of
      ARALAR-deficiency is neuronal, this explains the lack of accumulation of brain
      lactate in ARALAR-deficiency in humans and mice. On the other hand, we find that
      the cytosolic and mitochondrial components of the glycerol phosphate shuttle are
      present in astrocytes with similar activities. This suggests that glycerol
      phosphate shuttle is the main NADH shuttle in astrocytes and explains the absence
      of effects of ARALAR-deficiency in these cells.

PMID- 28429369
TI  - Variation in brain anatomy in frogs and its possible bearing on their locomotor
      ecology.
AB  - Despite the long-standing interest in the evolution of the brain, relatively
      little is known about variation in brain anatomy in frogs. Yet, frogs are
      ecologically diverse and, as such, variation in brain anatomy linked to
      differences in lifestyle or locomotor behavior can be expected. Here we present a
      comparative morphological study focusing on the macro- and micro-anatomy of the
      six regions of the brain and its choroid plexus: the olfactory bulbs, the
      telencephalon, the diencephalon, the mesencephalon, the rhombencephalon, and the
      cerebellum. We also report on the comparative anatomy of the plexus brachialis
      responsible for the innervation of the forelimbs. It is commonly thought that
      amphibians have a simplified brain organization, associated with their supposedly
      limited behavioral complexity and reduced motor skills. We compare frogs with
      different ecologies that also use their limbs in different contexts and for other
      functions. Our results show that brain morphology is more complex and more
      variable than typically assumed. Moreover, variation in brain morphology among
      species appears related to locomotor behavior as suggested by our quantitative
      analyses. Thus we propose that brain morphology may be related to the locomotor
      mode, at least in the frogs included in our analysis.

PMID- 28429370
TI  - The role of charged residues in independent glycine receptor folding domains for
      intermolecular interactions and ion channel function.
AB  - Glycine receptor (GlyR) truncations in the intracellular TM3-4 loop, documented
      in patients suffering from hyperekplexia and in the mouse mutant oscillator, lead
      to non-functionality of GlyRs. The missing part that contains the TM3-4 loop, TM4
      and C-terminal sequences is essential for pentameric receptor arrangements. In
      vitro co-expressions of GlyRalpha1-truncated N-domains and C-domains were able to
      restore ion channel function. An ionic interaction between both domains was
      hypothesized as the underlying mechanism. Here, we analysed the proposed ionic
      interaction between GlyR N- and C-domains using C-terminal constructs with either
      positively or negatively charged N-termini. Charged residues at the N-terminus of
      the C-domain did interfere with receptor surface expression and ion channel
      function. In particular, presence of negatively charged residues at the N
      terminus led to significantly decreased ion channel function. Presence of
      positive charges resulted in reduced maximal currents possibly as a result of
      repulsion of both domains. If the C-domain was tagged by a myc-epitope, low
      maximal current amplitudes were detected. Intrinsic charges of the myc-epitope
      and charged N-terminal ends of the C-domain most probably induce intramolecular
      interactions. These interactions might hinder the close proximity of C-domains
      and N-domains, which is a prerequisite for functional ion channel configurations.
      The remaining basic subdomains close to TM3 and 4 were sufficient for domain
      complementation and functional ion channel formation. Thus, these basic
      subdomains forming alpha-helical elements or an intracellular portal represent
      attractants for incoming negatively charged chloride ions and interact with the
      phospholipids thereby stabilizing the GlyR in a conformation that allows ion
      channel opening.

PMID- 28429371
TI  - Design of a short nonuniform acquisition protocol for quantitative analysis in
      dynamic cardiac SPECT imaging - a retrospective 123 I-MIBG animal study.
AB  - PURPOSE: Our previous works have found that quantitative analysis of 123 I-MIBG
      kinetics in the rat heart with dynamic single-photon emission computed tomography
      (SPECT) offers the potential to quantify the innervation integrity at an early
      stage of left ventricular hypertrophy. However, conventional protocols involving
      a long acquisition time for dynamic imaging reduce the animal survival rate and
      thus make longitudinal analysis difficult. The goal of this work was to develop a
      procedure to reduce the total acquisition time by selecting nonuniform
      acquisition times for projection views while maintaining the accuracy and
      precision of estimated physiologic parameters. METHOD: Taking dynamic cardiac
      imaging with 123 I-MIBG in rats as an example, we generated time activity curves
      (TACs) of regions of interest (ROIs) as ground truths based on a direct four
      dimensional reconstruction of experimental data acquired from a rotating SPECT
      camera, where TACs represented as the coefficients of B-spline basis functions
      were used to estimate compartmental model parameters. By iteratively adjusting
      the knots (i.e., control points) of B-spline basis functions, new TACs were
      created according to two rules: accuracy and precision. The accuracy criterion
      allocates the knots to achieve low relative entropy between the estimated left
      ventricular blood pool TAC and its ground truth so that the estimated input
      function approximates its real value and thus the procedure yields an accurate
      estimate of model parameters. The precision criterion, via the D-optimal method,
      forces the estimated parameters to be as precise as possible, with minimum
      variances. Based on the final knots obtained, a new protocol of 30 min was built
      with a shorter acquisition time that maintained a 5% error in estimating rate
      constants of the compartment model. This was evaluated through digital
      simulations. RESULTS: The simulation results showed that our method was able to
      reduce the acquisition time from 100 to 30 min for the cardiac study of rats with
      123 I-MIBG. Compared to a uniform interval dynamic SPECT protocol (1 s
      acquisition interval, 30 min acquisition time), the newly proposed protocol with
      nonuniform interval achieved comparable (K1 and k2, P = 0.5745 for K1 and P =
      0.0604 for k2) or better (Distribution Volume, DV, P = 0.0004) performance for
      parameter estimates with less storage and shorter computational time. CONCLUSION:
      In this study, a procedure was devised to shorten the acquisition time while
      maintaining the accuracy and precision of estimated physiologic parameters in
      dynamic SPECT imaging. The procedure was designed for 123 I-MIBG cardiac imaging
      in rat studies; however, it has the potential to be extended to other
      applications, including patient studies involving the acquisition of dynamic
      SPECT data.

PMID- 28429372
TI  - Long-term clinical impact of PSA surge in castration-resistant prostate cancer
      patients treated with abiraterone.
AB  - BACKGROUND: Early changes in PSA have been evaluated in association to treatment
      outcome. The aim of this study was to assess PSA surge phenomenon in castration
      resistant prostate cancer (CRPC) patients treated with abiraterone and to
      correlate those variations with long-term treatment outcome. PATIENTS AND
      METHODS: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals,
      monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical
      and molecular parameters were determined at baseline. We considered PSA surge as
      PSA increase within the first 8 weeks from starting abiraterone more than 1% from
      baseline followed by a PSA decline. The log-rank test was applied to compare
      survival between groups of patients according to PSA surge. The impact of PSA
      surge on survival was evaluated by Cox regression analyses. RESULTS: A total of
      330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone
      (281 chemotherapy-treated and 49 chemotherapy-naive). PSA surge was observed in
      20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naive patients. For overall
      patients presenting PSA surge, timing of PSA peak from baseline was 5 +/- 1.8
      weeks and PSA rise from baseline was 21 +/- 18.4%. The overall median follow-up
      was 23 months (range 1-62). No significant differences in progression-free
      survival and overall survival were observed between patients with and without PSA
      surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate
      analyses showed no baseline factors related to PSA surge. CONCLUSION: PSA surge
      occurs in both chemotherapy-treated and chemotherapy-naive patients treated with
      abiraterone resulting, however, in no long-term impact on outcome. Physicians and
      patients should be aware of PSA surge challenge to prevent a premature
      discontinuation of potentially effective therapy with abiraterone. Further larger
      and prospective studies are warranted to investigate this not infrequent
      phenomenon.

PMID- 28429373
TI  - Dietary shifts have consequences for the repertoire of allergens produced by the
      European house dust mite.
AB  - Products manufactured from mass-cultured house dust mites, currently
      commercialized for the diagnosis and immunotherapy of allergy, are heterogeneous
      in terms of allergen composition and thus present concerns to regulatory
      authorities. The most abundant species, Dermatophagoides pteronyssinus
      (Trouessart) (Astigmata: Pyroglyphidae), produces 19 allergenic proteins. Many of
      these are putatively involved in mite digestive physiology and metabolism. This
      study aimed to evaluate the effects of mite-rearing media on allergen production.
      Mites were adapted to feed on culture media supplemented with proteins, lipids,
      carbohydrates or beard shavings, and collected to quantify major allergens (Der p
      1 and 2) by immunodetection, transcription of allergen genes by real-time
      quantitative polymerase chain reaction, and allergen-related enzymatic
      activities. All culture media significantly affected the content of major
      allergens. Modification of macronutrients in the diet produced minor effects on
      the transcription of allergen genes, but significantly altered mite allergen
      related activities. The most remarkable impacts were detected in mites feeding on
      beard shavings and were reflected in reductions in the content of major
      allergens, alterations in the transcription of nine allergen genes, and changes
      in eight allergen-related activities. These results demonstrate the importance of
      culture media to the quality and consistency of mite extracts used for
      pharmaceuticals, and highlight the need to further elucidate allergen production
      by mites in the laboratory and in domestic environments.

PMID- 28429374
TI  - Immune responses to highly conserved influenza A virus matrix 1 peptides.
AB  - Influenza vaccine development is considered to be complicated and challenging.
      Constantly evolving influenza viruses require continuous global monitoring and
      reformulation of the vaccine strains. Peptides that are conserved among different
      strains and subtypes of influenza A virus are strongly considered to be
      attractive targets for development of cross protective influenza vaccines that
      stimulate cellular responses. In this study, three highly conserved (>90%) matrix
      1 peptides that contain multiple T cell epitopes, ILGFVFTLTVPSERGLQRRRF (PM 1),
      LIRHENRMVLASTTAKA (PM 2) and LQAYQKRMGVQMQR (PM 3), were assessed for their
      immunogenic potential in vitro by subjecting peripheral blood mononuclear cells
      from healthy volunteers to repetitive stimulation with these chemically
      synthesised peptides and measuring their IFN-gamma concentrations, proliferation
      by ELISA, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,
      respectively. Seven samples were screened for immunogenicity of PM 1 and PM 2,
      and six for that of PM 3. All six samples had positive responses (IFN-gamma
      secretion) to PM 3 stimulation, as did five and three for PM 2 and PM 1
      respectively. In contrast, seven (PM 1 and PM 2) and four (PM 3) samples showed
      proliferative response as compared with unstimulated cells. The encouraging
      immunogenic response generated by these highly conserved matrix 1 peptides
      indicates they are prospective candidates for development of broadly reactive
      influenza vaccines.

PMID- 28429375
TI  - Patient Characteristics and Outcomes Related to Successful Outpatient Competency
      Restoration.
AB  - Criminal defendants have a fundamental right to a fair and speedy trial. However,
      individuals found incompetent to stand trial are unable to move forward in the
      adjudication process and are often mired in protracted legal proceedings. If
      competency restoration is statutorily permissible and can be conducted in the
      outpatient setting, we propose that it should be considered based on burgeoning
      empirical data. We present data from an outpatient forensic clinic in which
      individuals are conditionally released to receive competency restoration in the
      community. Results indicated that three variables, including being single/never
      married, having comorbid intellectual disability and mental illness, and having
      one's conditional release revoked, were negatively related to successful
      restoration. The final model explained approximately one-third of the variance in
      restorability and correctly classified 75% of cases. Results demonstrate that
      individuals can be safely released to the community and successfully restored to
      competency in the outpatient setting. Utilizing outpatient competency restoration
      would not only reduce strain on inpatient facilities, but would also reduce the
      cost of treatment. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28429376
TI  - Daily crying prevalence and associated factors in older adult persons living in
      nursing homes: findings from a regional study.
AB  - OBJECTIVES: The study aims to evaluate the prevalence of nursing home (NH)
      resident crying and associated factors at the individual and NH levels. DESIGN: A
      regional retrospective study design has been used. PARTICIPANTS AND SETTING: A
      total of 8875 residents, living in 105 NHs, were included. MEASUREMENTS: The
      occurrence of an episode of crying on at least a daily basis in the last month
      was the dependent variable; independent variables were set at individual and at
      the NH levels as reported in the Val.Graf regional database. RESULTS: A total of
      1,443 (16.3%) residents reported daily episodes of crying over the last month.
      Several individual variables were significantly associated with crying; female
      gender (odds ratio [OR] 2.535, 95% confidence interval [CI] 2.069-3.107); sad,
      pained or worried facial expressions (OR 1.885, 95% CI 1.785-2.021); negative
      thoughts (OR 1.650, 95% CI 1.508-1.804); unrealistic fears (OR 1.410, 95% CI
      1.295-1.534); anger with self or others (OR 1.141, 95% CI 1.043-1.248);
      repetitive anxious complaints/concerns (OR 1.136, 95% CI 1.045-1.235); clinical
      instability (OR 1.186, 95% CI 1.018-1.381); pain (OR 1.183, 95% CI 1.058-1.323);
      night restlessness (OR 1.180, 95% CI 1.100-1.267); communication problems (OR
      1.169, 95% CI 1.051-1.300); and cognitive impairment (OR 1.086, 95% CI 1.019
      1.156); all increased the likelihood of crying. Conversely, sociability (OR
      0.866, 95% CI 0.805-0.932) and being involved in social based activities (OR
      0.882, 95% CI 0.811-0.960) were protective against crying. However, the
      previously mentioned variables have explained only 35.9% of variance in daily
      crying. CONCLUSIONS: Around one out of six residents living in NH cries on a
      daily basis, and the reasons are also at the individual level. Residents seem to
      cry for attachment and clinical needs and to express stress and unhappiness; more
      research is needed, aiming at discovering other factors associated with
      resident's daily crying. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28429377
TI  - Olfactory training with older people.
AB  - BACKGROUND/OBJECTIVES: Loss of olfactory function is largely found with aging.
      Such a reduction in olfactory function affects quality of life and enhances
      likelihood of depressive symptoms. Furthermore, it has been shown that reduction
      in olfactory function is associated with cognitive impairment and several
      diseases such as major depression. Because several studies suggest that
      discontinuous exposure to odors may improve general olfactory function, the
      primary aim of this study was to investigate whether such "olfactory training"
      has positive effects on subjective well-being and cognitive function. DESIGN: We
      performed a controlled, unblinded, longitudinal study SETTING: The study took
      place at an outpatients' clinic of a Department of Otorhinolaryngology at a
      Medical University. PARTICIPANTS: A total of 91 participants (age 50 to 84 years)
      completed testing. They were randomly assigned to an olfactory training (OT)
      group (N = 60) and a control group (N = 31). The study included two appointments
      at the Smell and Taste Clinic. MEASUREMENTS: Olfactory and cognitive function as
      well as subjective well-being was tested using standardized tests. INTERVENTION:
      During the 5-month interval between sessions, the OT group completed daily
      olfactory exposure. During the same time, the control group completed daily
      Sudoku problems. RESULTS: Analyses show a significant improvement of olfactory
      function for participants in the OT group and improved verbal function and
      subjective well-being. In addition, results indicated a decrease of depressive
      symptoms. CONCLUSION: Based on the present results, OT may constitute an
      inexpensive, simple way to improve quality of life in older people. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 28429378
TI  - Expanding access to naloxone for family members: The Massachusetts experience.
AB  - INTRODUCTION AND AIMS: The Massachusetts Department of Public Health Overdose
      Education and Naloxone Distribution Program provides overdose education and
      naloxone rescue kits to people at risk for overdose and bystanders, including
      family members. Using Massachusetts Department of Public Health data, the aims
      are to: (i) describe characteristics of family members who receive naloxone; (ii)
      identify where family members obtain naloxone; and (iii) describe characteristics
      of rescues by family members. DESIGN AND METHODS: We conducted a retrospective
      review using program enrollee information collected on a standardised form
      between 2008 and 2015. We calculated descriptive statistics, including
      demographics, current substance use, enrolment location, history of witnessed
      overdoses and rescue attempt characteristics. We conducted a stratified analysis
      comparing family members who used drugs with those who did not. RESULTS: Family
      members were 27% of total program enrollees (n = 10 883/40 801). Family members
      who reported substance use (n = 4679) were 35.6 years (mean), 50.6% female, 76.3%
      non-Hispanic white, 75.6% had witnessed an overdose, and they obtained naloxone
      most frequently at HIV prevention programs. Family members who did not report
      substance use (n = 6148) were 49.2 years (mean), 73.8% female, 87.9% non-Hispanic
      white, 35.3% had witnessed an overdose, and they obtained naloxone most
      frequently at community meetings. Family members were responsible for 20% (n =
      860/4373) of the total rescue attempts. DISCUSSION AND CONCLUSIONS: The
      Massachusetts experience demonstrates that family members can be active
      participants in responding to the overdose epidemic by rescuing family members
      and others. Targeted intervention strategies for families should be included in
      efforts to expand overdose education and naloxone in Massachusetts.

PMID- 28429380
TI  - Research on micro-damage behavior of wool fabrics drying in domestic dryer.
AB  - To evaluate the performance degradation of fabric drying in domestic air-vented
      dryer, the appearance, mechanical, and microscopic properties of the wool fabric
      after different drying cycles were studied. Pilling and dimensional stability
      tests were performed according to established international standards.
      Microscopic studies were carried out by Scanning Electron Microscopy (SEM) and X
      ray (XRD). The results show that pilling is the dominant damage mechanism and
      gradually increased during lower number of drying cycles (0-10 cycles). The
      results of dimensional stability showed that the highest dimensional shrinkage of
      knit wool fabric was first five drying cycles, and then increased at a relatively
      slow rate with the increase in drying cycles. And fabric shrinkage takes place
      mainly in the warp direction. The SEM images of wool fiber showed that the scales
      on the fiber surface were intact in the first 15 drying cycles but start to flake
      after 20 drying cycles. In the drying process, fabrics can suffer several
      fractures such as cut fracture, split fracture, partial fracture and distortion
      and even scale flaking and interior structural distortion of fiber. The damages
      occur quite randomly, but complexity and severity of damages increased with
      increase in drying cycles. XRD analysis showed that drying had little effect on
      fiber crystallinity, indicating that drying only leads to changes in the physical
      properties of wool fabrics instead of changes in the chemical composition of the
      fiber. And found SEM analysis is not only an effective method to characterize the
      change in the surface morphology of the fibers resulting from the drying
      treatments, but also explain the cause of fabric performance degradation such as
      pilling and strength reduction during drying.

PMID- 28429379
TI  - Retrospective evaluation of thoracic computed tomography findings in dogs
      naturally infected by Angiostrongylus vasorum.
AB  - Angiostrongylus vasorum (A. vasorum) is an important emerging disease of canidae.
      Cardiorespiratory signs are common in affected dogs, therefore thoracic imaging
      is critical for diagnosing and monitoring disease. Descriptions of thoracic
      computed tomography (CT) findings in dogs naturally infected with A. vasorum are
      currently lacking. Aims of this multicenter, retrospective study were to describe
      thoracic CT findings in a group of dogs with confirmed disease, determine whether
      any changes were consistent among dogs, and propose standardized terms for
      describing thoracic CT findings. Nine UK-based referral centers' clinical and
      imaging databases were searched for dogs that had a confirmed diagnosis of A.
      vasorum, and had undergone thoracic CT examination. Eighteen dogs, from seven of
      the centers, fulfilled the inclusion criteria. The lung lobes were divided into
      the following three zones and the CT changes described in each: pleural (zone 1),
      subpleural (zone 2), and peribronchovascular (zone 3). The predominent
      abnormality was increased lung attenuation due to poorly defined ground-glass
      opacity or consolidation. There were regions of mosaic attenuation due to
      peripheral bronchiectasis. Nine/18 (50%) dogs showed hyperattenuating nodules of
      varying sizes with ill-defined margins. The distribution always affected zones 1
      and 2 with varied involvement of zone 3; this resulted in clear delineation
      between zones 2 and 3. Tracheobronchial lymphadenomegaly was frequently noted.
      Findings were nonspecific and there was considerable overlap with other pulmonary
      conditions. However, authors recommend that A. vasorum be considered a likely
      differential diagnosis for dogs with a predominantly peripheral distribution of
      lung changes.

PMID- 28429381
TI  - The structural connectome of children with traumatic brain injury.
AB  - This study aimed to investigate the impact of mild to severe pediatric TBI on the
      structural connectome. Children aged 8-14 years with trauma control (TC) injury
      (n = 27) were compared to children with mild TBI and risk factors for complicated
      TBI (mildRF+ , n = 20) or moderate/severe TBI (n = 16) at 2.8 years post-injury.
      Probabilistic tractography on diffusion tensor imaging data was used in
      combination with graph theory to study structural connectivity. Functional
      outcome was measured using neurocognitive tests and parent and teacher
      questionnaires for behavioral functioning. The results revealed no evidence for
      an impact of mildRF+ TBI on the structural connectome. In contrast, the
      moderate/severe TBI group showed longer characteristic path length (P = 0.022, d
      = 0.82) than the TC group. Furthermore, longer characteristic path length was
      related to poorer intelligence and poorer working memory in children with TBI. In
      conclusion, children have abnormal organization of the structural connectome
      after moderate/severe TBI, which may be implicated in neurocognitive dysfunction
      associated with pediatric TBI. These findings should be interpreted in the
      context of our exploratory analyses, which indicate that the definition and
      weighting of connectivity (e.g., streamline density, fractional anisotropy)
      influence the properties of the reconstructed connectome and its sensitivity to
      the impact and outcome of pediatric TBI. Hum Brain Mapp, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28429382
TI  - Direct measurement of clinical mammographic x-ray spectra using a CdTe
      spectrometer.
AB  - PURPOSE: To introduce and evaluate a method developed for the direct measurement
      of mammographic x-ray spectra using a CdTe spectrometer. The assembly of a
      positioning system and the design of a simple and customized alignment device for
      this application is described. METHODS: A positioning system was developed to
      easily and accurately locate the CdTe detector in the x-ray beam. Additionally,
      an alignment device to line up the detector with the central axis of the
      radiation beam was designed. Direct x-ray spectra measurements were performed in
      two different clinical mammography units and the measured x-ray spectra were
      compared with computer-generated spectra. In addition, the spectrometer
      misalignment effect was evaluated by comparing the measured spectra when this
      device is aligned relatively to when it is misaligned. RESULTS: The positioning
      and alignment of the spectrometer have allowed the measurements of direct
      mammographic x-ray spectra in agreement with computer-generated spectra. The most
      accurate x-ray spectral shape, related with the minimal HVL value, and high
      photon fluence for measured spectra was found with the spectrometer aligned
      according to the proposed method. The HVL values derived from both simulated and
      measured x-ray spectra differ at most 1.3 and 4.5% for two mammography devices
      evaluated in this study. CONCLUSION: The experimental method developed in this
      work allows simple positioning and alignment of a spectrometer for x-ray spectra
      measurements given the geometrical constraints and maintenance of the original
      configurations of mammography machines.

PMID- 28429383
TI  - Altered eigenvector centrality is related to local resting-state network
      functional connectivity in patients with longstanding type 1 diabetes mellitus.
AB  - INTRODUCTION: Longstanding type 1 diabetes (T1DM) is associated with
      microangiopathy and poorer cognition. In the brain, T1DM is related to increased
      functional resting-state network (RSN) connectivity in patients without, which
      was decreased in patients with clinically evident microangiopathy. Subcortical
      structure seems affected in both patient groups. How these localized alterations
      affect the hierarchy of the functional network in T1DM is unknown. Eigenvector
      centrality mapping (ECM) and degree centrality are graph theoretical methods that
      allow determining the relative importance (ECM) and connectedness (degree
      centrality) of regions within the whole-brain network hierarchy. METHODS:
      Therefore, ECM and degree centrality of resting-state functional MRI-scans were
      compared between 51 patients with, 53 patients without proliferative retinopathy,
      and 49 controls, and associated with RSN connectivity, subcortical gray matter
      volume, and cognition. RESULTS: In all patients versus controls, ECM and degree
      centrality were lower in the bilateral thalamus and the dorsal striatum, with
      lowest values in patients without proliferative retinopathy (PFWE  < 0.05).
      Increased ECM in this group versus patients with proliferative retinopathy was
      seen in the bilateral lateral occipital cortex, and in the right cuneus and
      occipital fusiform gyrus versus controls (PFWE  < 0.05). In all patients, ECM and
      degree centrality were related to altered visual, sensorimotor, and auditory and
      language RSN connectivity (PFWE  < 0.05), but not to subcortical gray matter
      volume or cognition (PFDR  > 0.05). CONCLUSION: The findings suggested
      reorganization of the hierarchy of the cortical connectivity network in patients
      without proliferative retinopathy, which is lost with disease progression.
      Centrality seems sensitive to capture early T1DM-related functional connectivity
      alterations, but not disease progression. Hum Brain Mapp, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28429384
TI  - Enantioselective Silver and Amine Co-catalyzed Desymmetrizing Cycloisomerization
      of Alkyne-Linked Cyclohexanones.
AB  - A silver(I) and amine co-catalyzed desymmetrization of 4-propargylamino
      cyclohexanones for the direct enantioselective synthesis of 2
      azabicyclo[3.3.1]nonanes is described. Exploiting reactivity arising from dual
      activation of the pendant terminal alkyne by silver(I) and the ketone moiety
      through transient enamine formation, this synthetically relevant transformation
      is easy to perform, efficient and broad in scope. High enantioselectivity (up to
      96 % ee) was achieved by exploiting a significant matching effect between the
      chirality of a cinchona alkaloid-derived aminophosphine ligand for the silver(I)
      salt and the 2-bis(aryl)methylpyrrolidine catalyst which was rationalized by DFT
      calculations. This allowed for the preparation of both enantiomers of the
      bicyclic product with near-identical stereocontrol.

PMID- 28429385
TI  - Risk Factors Proximate to Suicide and Suicide Risk Assessment in the Context of
      Denied Suicide Ideation.
AB  - Health care providers have significant opportunities to identify individuals at
      near-term risk for suicide, but lack empirical data on near-term risk factors.
      This study aimed to identify dynamic, state-related risk factors observed by
      clinical practitioners within the last 30 days of life of 157 patients who died
      by suicide and to compare these near-term risk factors among patients who denied
      versus responded positively to having suicide ideation (SI) when last asked by a
      clinical practitioner prior to their death. Risk factors charted for the majority
      of all decedents were a history of prior suicide ideation and/or suicide attempt,
      current anxiety/agitation and sleep problems, current interpersonal problems or
      job/financial strain, current comorbid diagnoses, current social
      isolation/withdrawal, and a family history of mental disorder. Two-thirds of
      patients denied having SI when last asked and one-half of these patients were
      dead by suicide within 2 days. Decedents who denied having SI were quite similar
      in charted diagnoses, symptoms, behaviors, and environmental circumstances to
      decedents who responded affirmatively to having SI. Reliance on verbalized or
      reported SI as a gateway to a suicide risk assessment is questioned and the need
      for better understanding near-term risk for suicide, particularly in the absence
      of stated SI, is highlighted.

PMID- 28429386
TI  - Relationship between desired weight and eating disorder pathology in youth.
AB  - OBJECTIVE: Individuals with eating disorders (ED), particularly anorexia nervosa
      (AN), and bulimia nervosa (BN), often wish to reduce their body weight in pursuit
      of a thin ideal, but no study has examined the relation between desired weight
      and ED pathology in a clinical population of youth. Given the potential impact of
      desired weight on normalization of eating patterns and weight restoration, we
      examined the relation between desired weight and ED pathology in youth with AN or
      BN. METHODS: Participants were 340 youth presenting to an outpatient ED clinical
      research program. Height and weight were measured, and youth completed the Eating
      Disorder Examination. Desired weight was operationalized as "desired weight
      percentage" (calculated as a percentage of expected body weight [EBW]) and
      "weight difference percentage" (actual weight minus desired weight, divided by
      actual weight and multiplied by 100). RESULTS: Youth with AN desired to be a
      lower percentage of their EBW than youth with BN (p < .001). However, youth with
      AN, on average, wanted to gain 5.28% of their body weight and youth with BN
      wanted to lose 13.60% (p < .001). Desired weight percentage and weight difference
      percentage were associated with greater ED psychopathology, controlling for ED
      diagnosis, age, and sex (ps < .001). DISCUSSION: Desired weight is associated
      with elevated ED psychopathology. Weight goals may shift as individuals progress
      through treatment; if they do not, then desired weight may be an important
      indicator of a lack of psychological progress.

PMID- 28429388
TI  - Layered Double Hydroxide Nanosheets with Multiple Vacancies Obtained by Dry
      Exfoliation as Highly Efficient Oxygen Evolution Electrocatalysts.
AB  - Layered double hydroxides (LDHs) with two-dimensional lamellar structures show
      excellent electrocatalytic properties. However, the catalytic activity of LDHs
      needs to be further improved as the large lateral size and thickness of the bulk
      material limit the number of exposed active sites. However, the development of
      efficient strategies to exfoliate bulk LDHs into stable monolayer LDH nanosheets
      with more exposed active sites is very challenging. On the other hand, the
      intrinsic activity of monolayer LDH nanosheets can be tuned by surface
      engineering. Herein, we have exfoliated bulk CoFe LDHs into ultrathin LDH
      nanosheets through Ar plasma etching, which also resulted in the formation of
      multiple vacancies (including O, Co, and Fe vacancies) in the ultrathin 2D
      nanosheets. Owing to their ultrathin 2D structure, the LDH nanosheets expose a
      greater number of active sites, and the multiple vacancies significantly improve
      the intrinsic activity in the oxygen evolution reaction (OER).

PMID- 28429387
TI  - The association between GGCX, miR-133 genetic polymorphisms and warfarin stable
      dosage in Han Chinese patients with mechanical heart valve replacement.
AB  - WHAT IS KNOWN AND OBJECTIVE: Warfarin is a widely used anticoagulant with a
      narrow therapeutic index. Polymorphisms in the VKORC1, CYP2C9 and CYP4F2 genes
      have been verified to correlate with warfarin stable dosage (WSD). Whether any
      other genes or variants affect the dosage is unknown. The aim of our study was to
      investigate the relationship between GGCX, miR-133 variants and the WSD in Han
      Chinese patients with mechanical heart valve replacement (MHVR). METHODS: A total
      of 231 patients were enrolled in the study. Blood samples were collected for
      genotyping. The average WSD among subjects with different GGCX or miR-133
      genotypes was compared. Regression analyses were performed to test for any
      association of genetic polymorphisms with WSD. RESULTS AND DISCUSSION: The
      warfarin dosage in patients with the GGCX rs699664 TT and rs12714145 TT genotypes
      was 3.77+/-0.93 (95% CI: 3.35-4.19) mg/d and 3.70+/-1.00 (95% CI: 3.32-4.09)
      mg/d, respectively. The GGCX rs699664 and rs12714145 genotypes were significantly
      associated with WSD (P<.05). But they were ruled out in the multivariate
      regression analysis. There were no significant differences in the average
      warfarin stable dosage between subjects with MIR133B rs142410335 wild-type and
      variant genotypes (P>.05). WHAT IS NEW AND CONCLUSION: The genotypes of GGCX
      rs699644 and rs12714145 were significantly associated with WSD (P<.05), but their
      contributions were not significant after accounting for other factors. MIR133B
      rs142410335 makes no significant contributions to warfarin stable dosage in Han
      Chinese patients with MHVR neither in univariate regression nor in multivariate
      regression analyses.

PMID- 28429389
TI  - Evaluation of real-time data obtained from gravimetric preparation of
      antineoplastic agents shows medication errors with possible critical therapeutic
      impact: Results of a large-scale, multicentre, multinational, retrospective
      study.
AB  - WHAT IS KNOWN AND OBJECTIVE: Medication errors are a significant cause of
      morbidity and mortality especially with antineoplastic drugs, owing to their
      narrow therapeutic index. Gravimetric workflow software systems have the
      potential to reduce volumetric errors during intravenous antineoplastic drug
      preparation which may occur when verification is reliant on visual inspection.
      Our aim was to detect medication errors with possible critical therapeutic impact
      as determined by the rate of prevented medication errors in chemotherapy
      compounding after implementation of gravimetric measurement. DESIGN: A large
      scale, retrospective analysis of data was carried out, related to medication
      errors identified during preparation of antineoplastic drugs in 10 pharmacy
      services ("centres") in five European countries following the introduction of an
      intravenous workflow software gravimetric system. Errors were defined as errors
      in dose volumes outside tolerance levels, identified during weighing stages of
      preparation of chemotherapy solutions which would not otherwise have been
      detected by conventional visual inspection. KEY RESULTS: The gravimetric system
      detected that 7.89% of the 759 060 doses of antineoplastic drugs prepared at
      participating centres between July 2011 and October 2015 had error levels outside
      the accepted tolerance range set by individual centres, and prevented these doses
      from reaching patients. The proportion of antineoplastic preparations with
      deviations >10% ranged from 0.49% to 5.04% across sites, with a mean of 2.25%.
      The proportion of preparations with deviations >20% ranged from 0.21% to 1.27%
      across sites, with a mean of 0.71%. There was considerable variation in error
      levels for different antineoplastic agents. WHAT IS NEW AND CONCLUSION:
      Introduction of a gravimetric preparation system for antineoplastic agents
      detected and prevented dosing errors which would not have been recognized with
      traditional methods and could have resulted in toxicity or suboptimal therapeutic
      outcomes for patients undergoing anticancer treatment.

PMID- 28429390
TI  - Microporous Polyamide Membranes for Molecular Sieving of Nitrogen from Volatile
      Organic Compounds.
AB  - Microporous polymer membranes continue to receive tremendous attention for energy
      efficient gas separation processes owing to their high separation performances. A
      new network microporous polyamide membrane with good molecular-sieving
      performance for the separation of N2 from a volatile organic compound (VOC)
      mixture is described. Triple-substituted triptycene was used as the main monomer
      to form a fisherman's net-shaped polymer, which readily forms a composite
      membrane by solution casting. This membrane exhibited outstanding separation
      performance and good stability for the molecular-sieving separation of N2 over
      VOCs such as cyclohexane. The rejection rate of the membrane reached 99.2 % with
      2098 Barrer N2 permeability at 24  degrees C under 4 kPa. This approach promotes
      development of microporous membranes for separation of condensable gases.

PMID- 28429391
TI  - Technical Note: Direct measurement of continuous TMR data with a 1D tank and
      automated couch movements.
AB  - PURPOSE: Real-time dynamic control of the linear accelerator, couch, and imaging
      parameters during radiation delivery was investigated as a novel technique for
      acquiring tissue maximum ratio (TMR) data. METHODS: TrueBeam Developer Mode
      (Varian Medical Systems, Palo Alto, CA, USA) was used to control the linear
      accelerator using the Extensible Markup Language (XML). A single XML file was
      used to dynamically manipulate the machine, couch, and imaging parameters during
      radiation delivery. A TG-51 compliant 1D water tank was placed on the treatment
      couch, and used to position a detector at isocenter at a depth of 24.5 cm. A
      depth scan was performed towards the water surface. Via XML control, the
      treatment couch vertical position was simultaneously lowered at the same rate,
      maintaining the detector position at isocenter, allowing for the collection of
      TMR data. To ensure the detector remained at isocenter during the delivery, the
      in-room camera was used to monitor the detector. Continuous kV fluoroscopic
      images during 10 test runs further confirmed this result. TMR data at multiple
      Source to Detector Distances (SDD) and scan speeds were acquired to investigate
      their impact on the TMR data. Percentage depth dose (PDD) scans (for conversion
      to TMR) along with traditional discrete TMR data were acquired as a standard for
      comparison. RESULTS: More than 99.8% of the measured points had a gamma value
      (1%/1 mm) < 1 when compared with discrete or PDD converted TMR data. Fluoroscopic
      images showed that the concurrent couch and tank movements resulted in SDD errors
      < 1 mm. TMRs acquired at SDDs of 99, 100, and 101 cm showed differences less than
      0.004. CONCLUSION: TrueBeam Developer Mode was used to collect continuous TMR
      data with the same accuracy as traditionally collected discrete data, but yielded
      higher sampled resolution and reduced acquisition time. This novel method does
      not require the modification of any equipment and does not use a 3D tank or
      reservoir.

PMID- 28429392
TI  - Metal-Free Formal Oxidative C-C Coupling by In Situ Generation of an Enolonium
      Species.
AB  - Much contemporary organic synthesis relies on transformations that are driven by
      the intrinsic, so-called "natural", polarity of chemical bonds and reactive
      centers. The design of unconventionally polarized synthons is a highly desirable
      strategy, as it generally enables unprecedented retrosynthetic disconnections for
      the synthesis of complex substances. Whereas the umpolung of carbonyl centers is
      a well-known strategy, polarity reversal at the alpha-position of a carbonyl
      group is much rarer. Herein, we report the design of a novel electrophilic
      enolonium species and its application in efficient and chemoselective, metal-free
      oxidative C-C coupling.

PMID- 28429393
TI  - Synthesis and Evaluation of Thiazolidine Amide and N-Thiazolyl Amide
      Fluoroquinolone Derivatives.
AB  - In an effort to develop new fluoroquinolones, we synthesized eight compounds and
      tested them against a panel of bacteria. The design of these compounds was guided
      by the introduction of the isothiazoloquinolone motif. The three most active
      compounds in this series, 8-10, demonstrated good antibacterial activity against
      methicillin-sensitive Staphylococcus aureus and healthcare-acquired methicillin
      resistant Staphylococcus aureus (MIC 0.62-6.3 ug/mL). Further, when these three
      active compounds were tested for their inhibitory effects on bacterial enzymes,
      compound 9 was the most effective agent exhibiting IC50 values of 33.9 and 116.5
      MUM in the S. aureus deoxyribonucleic acid (DNA) gyrase supercoiling and
      topoisomerase IV decatenation assays, respectively.

PMID- 28429394
TI  - Immediate implant placement and restoration in the anterior maxilla: Tissue
      dimensional changes after 2-5 year follow up.
AB  - BACKGROUND: Immediate implant placement followed by an immediate restoration has
      proven to be a viable technique in the anterior maxillary region. PURPOSE: This
      prospective study evaluated the mid-long term (2-5 years) tissue changes around
      immediately placed and restored implants in the anterior maxilla using flapless
      surgery and simultaneous hard tissue augmentation. MATERIALS AND METHODS: Thirty
      AstraTech implants were immediately placed in 30 patients, followed by the
      delivery of an immediate provisional restoration on the same day. All
      participating 30 patients underwent the same treatment strategy that involved
      flapless removal of a failing maxillary anterior tooth, immediate implant
      placement, simultaneous augmentation with a deproteinized particulate xenograft,
      followed by the connection of a screw-retained provisional restoration.
      Radiographs and photographs were used to measure hard and soft tissue changes.
      Aesthetic evaluation was performed using the Pink Esthetic Score (PES). RESULTS:
      All implants remained osseointegrated during the follow up period of 2-5 years
      (mean 47 +/- 15 months). Twelve of the thirty patients completed the 5 year
      follow up. Radiographic evaluation revealed average gains in bone levels of 0.18
      and 0.34 mm mesially and distally, respectively. Soft tissue evaluation showed a
      mean tissue loss of 0.05 +/- 0.64 mm and 0.16 +/- 0.63 mm at the mesial and
      distal papillae, respectively, while mid-facial mucosal recession was 0.29 +/-
      0.74 mm. A significant improvement in the Pink Esthetic Scores was seen at the
      final follow-up (mean PES 11.50), as compared to the baseline (mean PES 10.27) (P
      = .001). CONCLUSIONS: In addition to a favorable implant success rate and peri
      implant bony response, the soft tissue levels and overall aesthetics around
      single immediately placed and restored implants can also be maintained in the mid
      long term.

PMID- 28429396
TI  - Children's Uncertain Responses when Testifying about Alleged Sexual Abuse in
      Scottish Courts.
AB  - This study examined the uncertain responses of 56 alleged sexual abuse victims,
      aged 5-17 years, testifying in Scottish criminal court trials. Don't
      know/remember ground rules were explained to 38% of the children and each child
      reported uncertainty in response to 15% of the questions on average. Uncertain
      responding was associated with expressions of resistance and confusion,
      questioning context (proportionally more regarding substantive than non
      substantive issues), question content (least to disclosure-focused questions),
      utterance type (more to directives, particularly those posed by defense lawyers;
      more to recall-based than recognition prompts), and age (children in mid
      adolescence were less likely to respond uncertainly than those who were either
      older or younger). There were no associations between expressions of uncertainty
      and ground rule administration, or with whether or not the question focused on
      central rather than peripheral details about the alleged crimes. Findings
      highlight concerns surrounding preparatory procedures to help witnesses,
      especially adolescents, indicate uncertainty when testifying. Copyright (c) 2017
      John Wiley & Sons, Ltd.

PMID- 28429395
TI  - ShRNA knock-down of CXCR7 inhibits tumour invasion and metastasis in
      hepatocellular carcinoma after transcatheter arterial chemoembolization.
AB  - To investigate the effects of lentiviral vector-mediated shRNA suppressing CXCR7
      on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after
      transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured
      and assigned into the CXCR7-shRNA, negative control (NC) and blank groups. The
      qRT-PCR and Western blotting were applied to detect the mRNA and protein
      expressions of CXCR7, CXCR4 and MMP-2 in HCCLM3 cells. Cell proliferation and
      invasion were evaluated by MTT and Transwell assays. A Buffalo rat model of HCC
      was established. Fifty model rats were divided into the CXCR7-shRNA + TACE, CXCR7
      shRNA, TACE, NC and control groups. Immunohistochemistry was performed to detect
      the expressions of CXCR7, MMP-2, vascular endothelial growth factor (VEGF) and
      intratumoral CD31-positive vessel count in tumour tissues of mice. Compared with
      the blank and NC groups, the mRNA and protein expressions of CXCR7 and MMP-2 were
      decreased in the CXCR7-shRNA group. The cell proliferation and invasion rates of
      the CXCR7-shRNA group were lower than the blank and NC groups. At the 4th week
      after TACE, tumour weight of the CXCR7-shRNA + TACE group increased continuously.
      The CXCR7-shRNA + TACE group showed longer survival time and smaller tumour sizes
      than other groups. Compared with other groups, the CXCR7-shRNA + TACE and CXCR7
      shRNA groups had less number of lung metastatic nodules and lower expressions of
      CXCR7, MMP-2, VEGF and CD31-positive vessel count. CXCR7-shRNA inhibits tumour
      invasion and metastasis to improve the efficacy of TACE in HCC by reducing the
      expressions of CXCR7, MMP-2 and VEGF.

PMID- 28429397
TI  - Natural hybridization and reproductive isolation between two Primula species.
AB  - Natural hybridization frequently occurs in plants and can facilitate gene flow
      between species, possibly resulting in species refusion. However, various
      reproductive barriers block the formation of hybrids and maintain species
      integrity. Here, we conducted a field survey to examine natural hybridization and
      reproductive isolation (RI) between sympatric populations of Primula secundiflora
      and P. poissonii using ten nuclear simple sequence repeat (SSR) loci. Although
      introgressive hybridization occurred, species boundaries between P. secundiflora
      and P. poissonii were maintained through nearly complete reproductive isolation.
      These interfertile species provide an excellent model for studying the RI
      mechanisms and evolutionary forces that maintain species boundaries.

PMID- 28429398
TI  - Efficacy of passive sampler collection for atmospheric NO2 isotopes under
      simulated environmental conditions.
AB  - RATIONALE: Nitrogen oxides or NOx (NOx = NO + NO2 ) play an important role in air
      quality, atmospheric chemistry, and climate. The isotopic compositions of
      anthropogenic and natural NO2 sources are wide-ranging, and they can be used to
      constrain sources of ambient NO2 and associated atmospheric deposition of
      nitrogen compounds. While passive sample collection of NO2 isotopes has been used
      in field studies to determine NOx source influences on atmospheric deposition,
      this approach has not been evaluated for accuracy or precision under different
      environmental conditions. METHODS: The efficacy of NO2 passive sampler collection
      for NO2 isotopes was evaluated under varied temperature and relative humidity
      (RH) conditions in a dynamic flux chamber. The precision and accuracy of the
      filter NO2 collection as nitrite (NO2- ) for isotopic analysis were determined
      using a reference NO2 gas tank and through inter-calibration with a modified EPA
      Method 7. The bacterial denitrifer method was used to convert 20 MUM of collected
      NO2- or nitrate (NO3- ) into N2 O and was carried out on an Isoprime continuous
      flow isotope ratio mass spectrometer. RESULTS: delta15 N-NO2 values determined
      from passive NO2 collection, in conditions of 11-34  degrees C, 1-78% RH, have an
      overall accuracy and precision of +/-2.1 0/00, and individual run precision of +/
      0.6 0/00. delta18 O-NO2 values obtained from passive NO2 sampler collection,
      under the same conditions, have an overall precision of +/- 1.3 0/00.
      CONCLUSIONS: Suitable conditions for passive sampler collection of NO2 isotopes
      are in environments ranging from 11 to 34  degrees C and 1 to 78% RH. The passive
      NO2 isotope measurement technique provides an accurate method to determine
      variations in atmospheric delta15 N-NO2 values and a precise method for
      determining atmospheric delta18 O-NO2 values. The ability to measure NO2 isotopes
      over spatial gradients at the same temporal resolution provides a unique
      perspective on the extent and seasonality of fluctuations in atmospheric NO2
      isotopic compositions. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28429399
TI  - Association of myocardial injury with increased mortality after liver
      transplantation.

PMID- 28429400
TI  - Circadian clock component, LHY, tells a plant when to respond photosynthetically
      to light in nature.
AB  - The circadian clock is known to increase plant growth and fitness, and is thought
      to prepare plants for photosynthesis at dawn and dusk; whether this happens in
      nature was unknown. We transformed the native tobacco, Nicotiana attenuata to
      silence two core clock components, NaLHY (irLHY) and NaTOC1 (irTOC1). We
      characterized growth and light- and dark-adapted photosynthetic rates (Ac )
      throughout a 24 h day in empty vector-transformed (EV), irLHY, and irTOC1 plants
      in the field, and in NaPhyA- and NaPhyB1-silenced plants in the glasshouse. The
      growth rates of irLHY plants were lower than those of EV plants in the field.
      While irLHY plants reduced Ac earlier at dusk, no differences between irLHY and
      EV plants were observed at dawn in the field. irLHY, but not EV plants, responded
      to light in the night by rapidly increasing Ac . Under controlled conditions, EV
      plants rapidly increased Ac in the day compared to dark-adapted plants at night;
      irLHY plants lost these time-dependent responses. The role of NaLHY in gating
      photosynthesis is independent of the light-dependent reactions and red light
      perceived by NaPhyA, but not NaPhyB1. In summary, the circadian clock allows
      plants not to respond photosynthetically to light at night by anticipating and
      gating red light-mediated in native tobacco.

PMID- 28429401
TI  - Synthesis of l-threitol-based crown ethers and their application as
      enantioselective phase transfer catalyst in Michael additions.
AB  - A few new l-threitol-based lariat ethers incorporating a monoaza-15-crown-5 unit
      were synthesized starting from diethyl l-tartrate. These macrocycles were used as
      phase transfer catalysts in asymmetric Michael addition reactions under mild
      conditions to afford the adducts in a few cases in good to excellent
      enantioselectivities. The addition of 2-nitropropane to trans-chalcone, and the
      reaction of diethyl acetamidomalonate with beta-nitrostyrene resulted in the
      chiral Michael adducts in good enantioselectivities (90% and 95%, respectively).
      The substituents of chalcone had a significant impact on the yield and
      enantioselectivity in the reaction of diethyl acetoxymalonate. The highest
      enantiomeric excess (ee) values (99% ee) were measured in the case of 4-chloro-
      and 4-methoxychalcone. The phase transfer catalyzed cyclopropanation reaction of
      chalcone and benzylidene-malononitriles using diethyl bromomalonate as the
      nucleophile (MIRC reaction) was also developed. The corresponding chiral
      cyclopropane diesters were obtained in moderate to good (up to 99%)
      enantioselectivities in the presence of the threitol-based crown ethers.

PMID- 28429402
TI  - Effectiveness of community-based interventions for reducing alcohol-related harm
      in two metropolitan and two regional sites in Victoria, Australia.
AB  - INTRODUCTION AND AIMS: The relationship between alcohol intoxication and harm is
      well known, and many community-based interventions have been introduced in an
      attempt to reduce the rates of alcohol-related harm. The current paper uses two
      metropolitan and two regional Australian cities as sites to investigate the
      impact of community-based interventions on the reduction of alcohol-related
      harms. DESIGN AND METHODS: Data for injury-related emergency department (ED)
      presentations and police attended assaults during high-alcohol hours (i.e. 20:00
      06:00 h, Friday and Saturday nights) were obtained for each site from 2000 to
      2015 for ED presentations and from 2000 to 2016 for police assaults.
      Autoregressive integrated moving average time series analyses were conducted to
      determine the impact of the community-based interventions introduced at each site
      for reducing these rates of ED injury presentations and police attended assaults.
      RESULTS: None of the community-level interventions that were introduced across
      the four sites resulted in a reduction in ED presentation rates or assault rates.
      DISCUSSION AND CONCLUSIONS: The majority of interventions introduced across the
      four sites were proposed and implemented by local liquor accords. Given none of
      the interventions demonstrated a reduction in ED injury presentation rates or
      police attended assault rates, it is argued that local liquor accords may not be
      best placed to propose alcohol-related harm reduction measures, and instead,
      there should be a focus on the implementation of evidence-based regulatory
      strategies, such as restricted trading hours. [Curtis A, Coomber K, Droste N,
      Hyder S, Palmer D, Miller PG. Effectiveness of community-based interventions for
      reducing alcohol-related harm in two metropolitan and two regional sites in
      Victoria, Australia. Drug Alcohol Rev 2017;36:359-368].

PMID- 28429403
TI  - Accuracy of computed tomographic arthrography for assessment of articular
      cartilage defects in the ovine stifle.
AB  - Articular cartilage defects are one of the features of osteoarthritis in animals
      and humans. Early detection of cartilage defects is a challenge in clinical
      veterinary practice and also in translational research studies. An accurate,
      diagnostic imaging method would be desirable for detecting and following up
      lesions in specific anatomical regions of the articular surface. The current
      prospective experimental study aimed to describe the accuracy of computed
      tomographic arthrography (CTA) for detecting cartilage defects in a common animal
      model used for osteoarthritis research, the ovine stifle (knee,
      femoropatellar/femorotibial) joint. Joints in cadaver limbs (n = 42) and in
      living animals under anesthesia (n = 13) were injected with a contrast medium and
      imaged using a standardized CT protocol. Gross anatomy and histological
      assessment of specific anatomic regions were used as a gold standard for the
      evaluation of sensitivity, specificity, negative predictive value, and positive
      predictive value for CTA identification of articular cartilage defects in those
      regions. Pooled estimated sensitivity and specificity were 90.32% and 97.30%,
      respectively, in cadaver limbs, and 81.82% and 95.24%, respectively, in living
      animals. Pooled estimated positive predictive value and negative predictive
      values were 98.25% and 85.71%, respectively, in cadaver limbs, and 81.82% and
      95.24%, respectively, in living animals. The delineation of cartilage surface was
      good for anatomical regions most frequently affected by cartilage defects in the
      ovine stifle: medial femoral condyle, medial tibial condyle, and patella. This
      study supported the use of CTA as an imaging technique for detecting and
      monitoring articular cartilage defects in the ovine stifle joint.

PMID- 28429404
TI  - Air pollution, weight loss and metabolic benefits of bariatric surgery: a
      potential model for study of metabolic effects of environmental exposures.
AB  - BACKGROUND: Emerging experimental evidence suggests that air pollution may
      contribute to development of obesity and diabetes, but studies of children are
      limited. OBJECTIVES: We hypothesized that pollution effects would be magnified
      after bariatric surgery for treatment of obesity, reducing benefits of surgery.
      METHODS: In 75 obese adolescents, excess weight loss (EWL), high-density
      lipoprotein (HDL) cholesterol, triglycerides, alkaline phosphatase (ALP) and
      hemoglobin A1c (HbA1c ) were measured prospectively at baseline and following
      laparoscopic adjustable gastric banding (LAGB). Residential distances to major
      roads and the average two-year follow-up exposure to particulate matter <2.5 MUm
      (PM2.5 ), nitrogen dioxide (NO2 ) and ozone were estimated. Associations of
      exposure with change in outcome and with attained outcome two years post-surgery
      were examined. RESULTS: Major-roadway proximity was associated with reduced EWL
      and less improvement in lipid profile and ALP after surgery. NO2 was associated
      with less improvement in HbA1c and lower attained HDL levels and change in
      triglycerides over two years post-surgery. PM2.5 was associated with reduced EWL
      and reduced beneficial change or attained levels for all outcomes except HbA1c .
      CONCLUSIONS: Near-roadway, PM2.5 and NO2 exposures at levels common in developed
      countries were associated with reduced EWL and metabolic benefits of LAGB. This
      novel approach provides a model for investigating metabolic effects of other
      exposures.

PMID- 28429405
TI  - Child body mass index, genotype and parenting in the prediction of restrictive
      feeding.
AB  - BACKGROUND: Restrictive feeding is implicated in pediatric obesity, and
      caregivers increase controlling feeding practices on the basis of higher child
      weight status. However, few studies have examined how child genetic and parenting
      characteristics together impact restrictive feeding. OBJECTIVES: We examined
      whether child body mass index (BMI) status predicts caregiver use of restrictive
      feeding and if this association is moderated by (i) caregiver strategies to
      manage their children's distress and (ii) child variations in the catechol-O
      methyltransferase (COMT) gene (Val158 Met, rs4680). METHODS: Participants
      included 126 Caucasian children (50% girls) and their caregivers who were
      participating in a larger study in the USA. Caregivers reported on their feeding
      practices and responses to child distress when children were 2.5-3.5 years of
      age. Child anthropometric measurements were also obtained. Restrictive feeding
      was assessed again 1-1.5 years later. Genomic DNA was obtained from saliva
      samples, and COMT-rs4680 was genotyped using TaqMan(r) methodology. RESULTS:
      Child BMI percentile predicted subsequent caregiver restrictive feeding for
      children who were Met/Met and who had caregivers reporting higher use of negative
      responses to child distress. For Val carriers, BMI percentile predicted
      restrictive feeding when caregivers were below the mean on these responses.
      CONCLUSIONS: Caregivers are at risk for use of restrictive feeding practices when
      their children are at higher BMI percentiles, and this association increases when
      caregivers use more ineffective stress regulation practices and their children
      are homozygous for the Met allele. Prevention programmes might focus on parenting
      behaviours that foster emotion regulation and consider variation in child
      responses to parenting.

PMID- 28429407
TI  - Spinal cord injury induces widespread chronic changes in cerebral white matter.
AB  - Traumatic spinal cord injuries (SCIs) lead to axonal damage at the trauma site,
      as well as disconnections within the central nervous system. While the exact
      mechanisms of the long-term pathophysiological consequences of SCIs are not fully
      understood, it is known that neuronal damage and degeneration are not limited to
      the direct proximity of the trauma. Instead, the effects can be detected even in
      the cerebrum. We examined SCI-induced chronic brain changes with a case-control
      design using 32 patients and 70 control subjects. Whole-brain white matter (WM)
      tracts were assessed with diffusion tensor imaging (DTI). In addition, we
      analysed associations between DTI metrics and several clinical SCI variables.
      Whole-brain analyses were executed by tract-based spatial statistics (TBSS), with
      an additional complementary atlas-based analysis (ABA). We observed widespread,
      statistically significant (P <= 0.01) changes similar to neural degeneration in
      SCI patients, both in the corticospinal tract (CST) and beyond. In addition,
      associations between DTI metrics and time since injury were found with TBSS and
      ABA, implying possible long-term post-injury neural regeneration. Using the ABA
      approach, we observed a correlation between SCI severity and DTI metrics,
      indicating a decrease in WM integrity along with patient sensory or motor scores.
      Our results suggest a widespread neurodegenerative effect of SCI within the
      cerebrum that is not limited to the motor pathways. Furthermore, DTI-measured WM
      integrity of chronic SCI patients seemed to improve as time elapsed since injury.
      Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28429406
TI  - Haplodeficiency of Cathepsin D does not affect cerebral amyloidosis and autophagy
      in APP/PS1 transgenic mice.
AB  - Autophagy and lysosomal function are important for protein homeostasis and their
      dysfunction have been associated with Alzheimer's disease (AD). Increased
      immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are
      evident in amyloid plaques and neurons in patients with AD. This study tests the
      hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts
      cerebral beta-amyloidosis in amyloid-beta precursor protein (APP)sw/PS1dE9
      (APP/PS1) double transgenic mice. Despite a significant 38% decrease in Cat D
      level in APP/PS1/Ctsd+/- compared with APP/PS1/Ctsd+/+ mice, no changes in steady
      state levels and deposition of Abeta were found in the brain. There were also no
      differences in APP processing, the levels of two other Abeta-degrading proteases,
      the levels of autophagy related protein, such as LAMP2, P62, LC3-I, LC3-II, and
      Beclin-1, or the markers of neuroinflammation, observed between the
      APP/PS1/Ctsd+/+ and APP/PS1/Ctsd+/- mice. Our findings demonstrate that in wild
      type mice, Cat D protein levels are either in excess or redundant with other
      factors in the brain, and at least one allele of Ctsd is dispensable for cerebral
      beta-amyloidosis and autophagy in APP/PS1 transgenic mice.

PMID- 28429408
TI  - Mo2 B4 O9 -Connecting Borate and Metal-Cluster Chemistry.
AB  - We report on the first thoroughly characterized molybdenum borate, which was
      synthesized in a high-pressure/high-temperature experiment at 12.3 GPa/1300 
      degrees C using a Walker-type multianvil apparatus. Mo2 B4 O9 incorporates
      tetrahedral molybdenum clusters into an anionic borate crystal structure-a
      structural motif that has never been observed before in the wide field of borate
      crystal chemistry. The six bonding molecular orbitals of the [Mo4 ] tetrahedron
      are completely filled with 12 electrons, which are fully delocalized over the
      four molybdenum atoms. This finding is in agreement with the results of the
      magnetic measurements, which confirmed the diamagnetic character of Mo2 B4 O9 .
      The two four-coordinated boron sites can be differentiated in the 11 B MAS-NMR
      spectrum because of the strongly different degrees of local distortions.
      Experimentally obtained IR and Raman bands were assigned to vibrational modes
      based on DFT calculations.

PMID- 28429409
TI  - Theoretical insights into the effect of pH values on oxidation processes in the
      emission of firefly luciferin in aqueous solution.
AB  - To elucidate the emission process of firefly d-luciferin oxidation across the pH
      range of 7-9, we identified the emission process by comparison of the potential
      and free-energy profiles for the formation of the firefly substrate and emitter,
      including intermediate molecules such as d-luciferyl adenylate, 4-membered
      dioxetanone, and their deprotonated chemical species. From these relative free
      energies, it is observed that the oxidation pathway changes from d-luciferin ->
      deprotonated d-luciferyl adenylate -> deprotonated 4-membered dioxetanone ->
      oxyluciferin to deprotonated d-luciferin -> deprotonated d-luciferyl adenylate ->
      deprotonated 4-membered dioxetanone -> oxyluciferin with increasing pH value.
      This indicates that deprotonation on 6'OH occurs during the formation of
      dioxetanone at pH 7-8, whereas luciferin in the reactant has a 6'OH-deprotonated
      form at pH 9.

PMID- 28429410
TI  - Photoelectroreduction of Building-Block Chemicals.
AB  - Conventional photoelectrochemical cells utilize solar energy to drive the
      chemical conversion of water or CO2 into useful chemical fuels. Such processes
      are confronted with general challenges, including the low intrinsic activities
      and inconvenient storage and transportation of their gaseous products. A
      photoelectrochemical approach is proposed to drive the reductive production of
      industrial building-block chemicals and demonstrate that succinic acid and
      glyoxylic acid can be readily synthesized on Si nanowire array photocathodes free
      of any cocatalyst and at room temperature. These photocathodes exhibit a positive
      onset potential, large saturation photocurrent density, high reaction
      selectivity, and excellent operation durability. They capitalize on the large
      photovoltage generated from the semiconductor/electrolyte junction to partially
      offset the required external bias, and thereby make this photoelectrosynthetic
      approach significantly more sustainable compared to traditional electrosynthesis.

PMID- 28429411
TI  - Nanodiscs for INPHARMA NMR Characterization of GPCRs: Ligand Binding to the Human
      A2A Adenosine Receptor.
AB  - G-protein-coupled-receptors (GPCRs) are of fundamental importance for signal
      transduction through cell membranes. This makes them important drug targets, but
      structure-based drug design (SBDD) is still hampered by the limitations for
      structure determination of unmodified GPCRs. We show that the interligand NOEs
      for pharmacophore mapping (INPHARMA) method can provide valuable information on
      ligand poses inside the binding site of the unmodified human A2A adenosine
      receptor reconstituted in nanodiscs. By comparing experimental INPHARMA spectra
      with back-calculated spectra based on ligand poses obtained from molecular
      dynamics simulations, a complex structure for A2A R with the low-affinity ligand
      3-pyrrolidin-1-ylquinoxalin-2-amine was determined based on the X-ray structure
      of ligand ZM-241,358 in complex with a modified A2A R.

PMID- 28429412
TI  - Bone extracellular matrix hydrogel enhances osteogenic differentiation of C2C12
      myoblasts and mouse primary calvarial cells.
AB  - Hydrogel scaffolds derived from the extracellular matrix (ECM) of mammalian
      tissues have been successfully used to promote tissue repair in vitro and in
      vivo. The objective of this study was to evaluate the osteogenic potential of ECM
      hydrogels prepared from demineralized and decellularized bovine bone in the
      presence and absence of osteogenic medium. Culture of C2C12 and mouse primary
      calvarial cells (mPCs) on decellularized bone ECM (bECM) and demineralized bone
      matrix (DBM) gels resulted in increased expression of osteogenic gene markers,
      including a 3.6- and 13.4-fold increase in osteopontin and 15.7- and 27.1-fold
      increase in osteocalcin when mPCs were cultured upon bECM with basal and
      osteogenic media, respectively. bECM hydrogels stimulated the osteogenic
      differentiation of C2C12 and mPCs even in the absence of osteogenic medium. These
      results suggest that bECM hydrogel scaffolds may have great utility in future
      clinical applications for bone tissue engineering. (c) 2017 Wiley Periodicals,
      Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 900-908, 2018.

PMID- 28429413
TI  - Vanadium(V)-Induced Oxidative Cross-Coupling of Various Boron and Silyl Enolates.
AB  - Intermolecular oxidative cross-coupling of two different enolates is one of the
      most useful reactions to synthesize unsymmetrical 1,4-dicarbonyl compounds. In
      this study, the oxovanadium(V)-induced intermolecular oxidative cross-coupling of
      enolates afforded unsymmetrical 1,4-dicarbonyl compounds. Various boron and silyl
      enolates underwent the formation of ketone-ester, ester-ketone, ester-ester,
      amide-ketone and amide-ester coupling products . These results clearly show the
      versatility of the present oxidative cross-coupling protocol.

PMID- 28429414
TI  - Evaluation of T2-weighted versus short-tau inversion recovery sagittal sequences
      in the identification and localization of canine intervertebral disc extrusion
      with low-field magnetic resonance imaging.
AB  - Sagittal T2-weighted sequences (T2-SAG) are the foundation of spinal protocols
      when screening for the presence of intervertebral disc extrusion. We often
      utilize sagittal short-tau inversion recovery sequences (STIR-SAG) as an
      adjunctive screening series, and experience suggests that this combined approach
      provides superior detection rates. We hypothesized that STIR-SAG would provide
      higher sensitivity than T2-SAG in the identification and localization of
      intervertebral disc extrusion. We further hypothesized that the parallel
      evaluation of paired T2-SAG and STIR-SAG series would provide a higher
      sensitivity than could be achieved with either independent sagittal series when
      viewed in isolation. This retrospective diagnostic accuracy study blindly
      reviewed T2-SAG and STIR-SAG sequences from dogs (n = 110) with surgically
      confirmed intervertebral disc extrusion. A consensus between two radiologists
      found no significant difference in sensitivity between T2-SAG and STIR-SAG during
      the identification of intervertebral disc extrusion (T2-SAG: 92.7%, STIR-SAG:
      94.5%, P = 0.752). Nevertheless, STIR-SAG accurately identified intervertebral
      disc extrusion in 66.7% of cases where the evaluation of T2-SAG in isolation had
      provided a false negative diagnosis. Additionally, one radiologist found that the
      parallel evaluation of paired T2-SAG and STIR-SAG series provided a significantly
      higher sensitivity than T2-SAG in isolation, during the identification of
      intervertebral disc extrusion (T2-SAG: 78.2%, paired T2-SAG, and STIR-SAG: 90.9%,
      P = 0.017). A similar nonsignificant trend was observed when the consensus of
      both radiologists was taken into consideration (T2-SAG: 92.7%, paired T2-SAG, and
      STIR-SAG = 97.3%, P = 0.392). We therefore conclude that STIR-SAG is capable of
      identifying intervertebral disc extrusion that is inconspicuous in T2-SAG, and
      that STIR-SAG should be considered a useful adjunctive sequence during
      preliminary sagittal screening for intervertebral disc extrusion in low-field
      magnetic resonance.

PMID- 28429415
TI  - Rod-Shaped Neural Units for Aligned 3D Neural Network Connection.
AB  - This paper proposes neural tissue units with aligned nerve fibers (called rod
      shaped neural units) that connect neural networks with aligned neurons. To make
      the proposed units, 3D fiber-shaped neural tissues covered with a calcium
      alginate hydrogel layer are prepared with a microfluidic system and are cut in an
      accurate and reproducible manner. These units have aligned nerve fibers inside
      the hydrogel layer and connectable points on both ends. By connecting the units
      with a poly(dimethylsiloxane) guide, 3D neural tissues can be constructed and
      maintained for more than two weeks of culture. In addition, neural networks can
      be formed between the different neural units via synaptic connections.
      Experimental results indicate that the proposed rod-shaped neural units are
      effective tools for the construction of spatially complex connections with
      aligned nerve fibers in vitro.

PMID- 28429416
TI  - Modulation of Heterotypic and Homotypic Cell-Cell Interactions via Zwitterionic
      Lipid Masks.
AB  - Since the pioneering work by Whitesides, innumerable platforms that aim to spatio
      selectively seed cells and control the degree of cell-cell interactions in vitro
      have been developed. These methods, however, have generally been technically and
      methodologically complex, or demanded stringent materials and conditions. In this
      work, we introduce zwitterionic lipids as patternable, cell-repellant masks for
      selectively seeding cells. The lipid masks are easily removed with a routine
      washing step under physiological conditions (37  degrees C, pH 7.4), and are used
      to create patterned cocultures, as well as to conduct cell migration studies. We
      demonstrate, via patterned cocultures of NIH 3T3 fibroblasts and HeLa cells, that
      HeLa cells proliferate far more aggressively than NIH 3T3 cells, regardless of
      initial population sizes. We also show that fibronectin-coated substrates induce
      cell movement akin to collective migration in NIH 3T3 fibroblasts, while the
      cells cultured on unmodified substrates migrate independently. Our lipid mask
      platform offers a rapid and highly biocompatible means of selectively seeding
      cells, and acts as a versatile tool for the study of cell-cell interactions.

PMID- 28429417
TI  - Immobilization methods for the rapid total chemical synthesis of proteins on
      microtiter plates.
AB  - The chemical synthesis of proteins typically involves the solid-phase peptide
      synthesis of unprotected peptide fragments that are stitched together in solution
      by native chemical ligation (NCL). The process is slow, and throughput is limited
      because of the need for repeated high performance liquid chromatography
      purification steps after both solid-phase peptide synthesis and NCL. With an aim
      to provide faster access to functional proteins and to accelerate the functional
      analysis of synthetic proteins by parallelization, we developed a method for the
      high performance liquid chromatography-free synthesis of proteins on the surface
      of microtiter plates. The method relies on solid-phase synthesis of unprotected
      peptide fragments, immobilization of the C-terminal fragment and on-surface NCL
      with an unprotected peptide thioester in crude form. Herein, we describe the
      development of a suitable immobilization chemistry. We compared (i) formation of
      nickel(II)-oligohistidine complexes, (ii) Cu-based [2 + 3] alkine-azide
      cycloaddition and (iii) hydrazone ligation. The comparative study identified the
      hydrazone ligation as most suitable. The sequence of immobilization via hydrazone
      ligation, on-surface NCL and radical desulfurization furnished the targeted SH3
      domains in near quantitative yield. The synthetic proteins were functional as
      demonstrated by an on-surface fluorescence-based saturation binding analysis.
      Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.

PMID- 28429418
TI  - The Dynamics of the Reaction of FeO+ and H2 : A Model for Inorganic Oxidation.
AB  - Extensive density functional theory (DFT) calculations using the B3LYP functional
      were used to explore the sextet and quartet energy potential energy surfaces
      (PESs) of the title reaction, and as a basis to fit global analytical reactive
      PESs. Surface-hopping dynamics on these PESs reproduce the experimentally
      observed reactivity and confirm that hydrogen activation rather than spin-state
      change is rate-limiting at low reaction energy, where the main products are Fe+
      and H2 O. A change in spin state is inefficient in the product region so that
      excited-state 4 Fe+ is the dominant product. At higher energies, spin-allowed
      hydrogen atom abstraction to form FeOH+ predominates. At intermediate energy, a
      previously unexpected rebound mechanism contributes significantly to the
      reactivity.

PMID- 28429419
TI  - Semi-synthesis of murine prion protein by native chemical ligation and chemical
      activation for preparation of polypeptide-alpha-thioester.
AB  - Prions are suspected as pathogen of the fatal transmissible spongiform
      encephalopathies. Strategies to access homogenous prion protein (PrP) are
      required to fully comprehend the molecular mechanism of prion diseases. However,
      the polypeptide fragments from PrP show a high tendency to form aggregates, which
      is a gigantic obstacle of protein synthesis and purification. In this study,
      murine prion sequence 90 to 230 that is the core three-dimensional structure
      domain was constructed from three segments murine PrP (mPrP)(90-177), mPrP(178
      212), and mPrP(213-230) by combining protein expression, chemical synthesis and
      chemical ligation. The protein sequence 90 to 177 was obtained from expression
      and finally converted into the polypeptide hydrazide by chemical activation of a
      cysteine in the tail. The other two polypeptide fragments of the C-terminal were
      obtained by chemical synthesis, which utilized the strategies of isopeptide and
      pseudoproline building blocks to complete the synthesis of such difficult
      sequences. The three segments were finally assembled by sequentially using native
      chemical ligation. This strategy will allow more straightforward access to
      homogeneously modified PrP variants. Copyright (c) 2017 European Peptide Society
      and John Wiley & Sons, Ltd.

PMID- 28429420
TI  - The crystal structure of a new O-demethylase from Sphingobium sp. strain SYK-6.
AB  - : In the cell, tetrahydrofolate (H4 folate) derivatives with a C1 unit are
      utilized in various ways, such as for the synthesis of amino acids and nucleic
      acids. While H4 folate derivatives with the C1 unit are typically produced in the
      glycine cleavage system, Sphingobium sp. strain SYK-6, which can utilize lignin
      derived aromatic compounds as a sole source of carbon and energy, lacks this
      pathway, probably due to its unique nutrient requirements. In this bacterium, H4
      folate-dependent O-demethylases in catabolic pathways for lignin-derived aromatic
      compounds seem to be involved in the C1 metabolism. LigM is one of the O
      demethylases and catalyzes a C1-unit transfer from vanillate (VNL) to H4 folate.
      As the primary structure of LigM shows a similarity to T-protein in the glycine
      cleavage system, we hypothesized that LigM has evolved from T-protein, acquiring
      its unique biochemical and biological functions. To prove this hypothesis,
      structure-based understanding of its catalytic reaction is essential. Here, we
      determined the crystal structure of LigM in apo form and in complex with
      substrates and H4 folate. These crystal structures showed that the overall
      structure of LigM is similar to T-protein, but LigM has a few distinct
      characteristics, particularly in the active site. Structure-based mutational
      analysis revealed that His60 and Tyr247, which are not conserved in T-protein,
      are essential to the catalytic activity of LigM and their interactions with the
      oxygen atom in the methoxy group of VNL seem to facilitate a methyl moiety (C1
      unit) transfer to H4 folate. Taken together, our structural data suggest that
      LigM has evolved divergently from T-protein. DATABASES: All atomic coordinates of
      the crystal structures determined in this study have been deposited to PDB. LigM:
      5X1I, LigM-VNL complex: 5X1J, LigM-3-O-methylgallate complex: 5X1K, LigM-H4
      folate complex: 5X1IL, LigM-H4 folate-protocatechuate (PCA) complex (P21 21 2):
      5X1M, LigM-H4 folate-PCA complex (P31 21): 5X1N.

PMID- 28429421
TI  - A Boat-Shaped Tetracationic Macrocycle with a Semiconducting Organic Framework.
AB  - We report the synthesis of a tetracationic macrocycle which contains two N,N'
      bis(methylene)naphthalenediimide units inserted in between the pyridinium rings
      of the bipyridinium units in cyclobis(paraquat-p-phenylene) (CBPQT4+ or "blue
      box") and describe the investigation of its potential use in materials for
      organic electronics. The incorporation of the two naphthalenediimide (NDI) units
      into the constitution of CBPQT4+ , not only changes the supramolecular properties
      of the tetracation in the solid state, but also has a profound influence on the
      electrochemical and electronic behavior of the resulting tetracationic
      macrocycle. In particular, the solid-state (super)structure, investigated by
      single-crystal X-ray diffraction, reveals the formation of a three-dimensional
      (3D) supramolecular framework with ca. 2.8 nm diameter one-dimensional (1D)
      hexagonal channels. Electrochemical studies on solid-state thin films of the
      macrocycle show that they exhibit semiconducting properties with a redox
      conductivity of up to 7.6*10-4  S m-1 . Moreover, EPR and ENDOR spectroscopies
      show that charge is equally shared between the NDIs within the one-electron
      reduced state of the NDI-based macrocycle on the time scale of these techniques.

PMID- 28429423
TI  - ERRATUM.

PMID- 28429422
TI  - Retrospective evaluation of premenopausal hormone-sensitive breast cancer
      patients treated with adjuvant gonadotropin-releasing hormone analogue: Anatolian
      Society of Medical Oncology (ASMO) study.
AB  - AIM: The goal of this study is to evaluate possible factors affecting the
      survival of patients treated with gonadotropin-releasing hormone (GnRH)
      analogues. METHODS: Demographic characteristics, treatment modalities, overall
      survival (OS) and the possible factors affecting the survival a total of 554
      premenopausal breast cancer patients in Turkey evaluated retrospectively.
      RESULTS: The median duration of GnRH analogues use was 22 +/- 13.6 (range, 1-87)
      months. Patients were divided into three groups according to the duration of GNRH
      analogues use; 4-12 months (Group A), 13-24 months (Group B) and >=25 months
      (Group C). Overall, 530 patients were analyzed; 23.2%, 45.8%, 30.9% of the
      patients were in Group A, B and C, respectively. The median follow-up duration
      was 34 +/- 30.3 (range, 4-188) months. The OS in patients <=35 years of age was
      found to be significantly longer than that of patients >35 years of age in Group
      B (log rank, P = 0.023). The disease-free survival of the patients in Group A was
      significantly shorter than that of patients in Group C (log rank, P = 0.003). The
      OS of Group A patients was significantly shorter in comparison to that of Group B
      and Group C patients (log rank, P = 0.000) and the OS of Group B patients was
      significantly shorter than Group C (log rank, P = 0,000). CONCLUSION: There is
      currently no definite data on the optimal duration of GnRH analogues use. One of
      the important results of this study that will provide an insight to the future
      studies is the improvement gained in OS by the increase in the duration of GnRH
      analogues use.

PMID- 28429424
TI  - Palladium-Catalyzed Carbonylation of sec- and tert-Alcohols.
AB  - A general palladium-catalyzed synthesis of linear esters directly from sec- and
      tert-alcohols is described. Compared to the classic Koch-Haaf reaction, which
      leads to branched products, this new transformation gives the corresponding
      linear esters in high yields and selectivity. Key for this protocol is the use of
      an advanced palladium catalyst system with L2 (pyt bpx) as the ligand. A variety
      of aliphatic and benzylic alcohols can be directly used and the catalyst
      efficiency for the benchmark reaction is outstanding (turnover number up to 89
      000).

PMID- 28429425
TI  - Accuracy of cytology in sub typing non small cell lung carcinomas.
AB  - BACKGROUND: Sub typing of non small cell lung carcinoma (NSCLC) has an important
      task in the era of molecular and targeted therapies. Differentiating between
      squamous cell carcinoma (SQCC) and adenocarcinoma (ADC) is challenging when
      limited material is available in lung carcinoma. We investigated the accuracy and
      feasibility of sub typing NSCLCs in cytology and small biopsy material. METHODS:
      Concurrent cytology and biopsy material obtained in a single CT- guided procedure
      in lung carcinoma over a year period retrospectively. Both materials were
      individually sub typed and analyzed. Immunohistochemistry (IHC) was performed.
      Accuracy was determined by comparing the results with IHC. RESULTS: Total 107 of
      126 cases of NSCLCs were included for analysis, where both cytology and biopsy
      material were adequate for interpretation. FNAC allowed tumor typing in 83
      (77.6%) cases; 36 (33.6%) were ADC, 47 (43.9%) cases were SQCC and 24 (22.4%)
      cases diagnosed as Non-small cell carcinoma not otherwise specified (NSCLC-NOS).
      In biopsy, 86 cases (80.4%) were typed, among which 34 (31.8%) were ADC, 52
      (48.6%) were SQCC and 21 (19.6%) were of NSCLC-NOS type. The result of Chi-square
      index was significant. With the aid of IHC, NSCLC-NOS reduced from 14 (13%) cases
      to 2 (1.9%) cases. CONCLUSION: Cytology and small biopsy specimens achieved
      comparable specificity and accuracy in sub-typing NSCLC and optimal results were
      obtain when findings from both modalities combine. The advantage of paired
      specimens is to maximize overall diagnostic yield and the remaining material will
      be available for ancillary technique like IHC or for molecular testing. Diagn.
      Cytopathol. 2017;45:598-603. (c) 2017 Wiley Periodicals, Inc.

PMID- 28429426
TI  - Age-related health care disparities in multiple myeloma.
AB  - Age is a well-known factor in solid tumours linked to lower adherence to
      guidelines. Scarce data exist for haematologic malignancies such as multiple
      myeloma (MM). The aim of the study was to investigate the relationships among
      age, adherence to guidelines in MM, and overall survival (OS).The Poitou
      Charentes cancer registry has exhaustively registered incident cases of MM from
      2008 to 2010. Diagnosis, staging, prognosis, and first-line treatment were
      compared to the international guidelines. Three hundred and sixty-seven patients
      aged 36 to 93 years were included. Compliance to diagnostic procedure was 98%,
      staging 62%, prognosis 30%, and first-line treatment 89%. Cytogenetic analysis
      was compliant in 37%. Younger age was the strongest factor associated with
      compliant provision of care (odds ratio 14.4 [6.1-33.8] for <66 years and 2.3
      [0.9-6.1] for 66-74 years; P < .0001). The second independent factor was active
      versus smouldering myeloma (odds ratio 3.5 [1.6-7.3]; P = .0009). Adherence to
      guidelines is related with OS in multivariate analysis hazard ratio: 1.6 [1.0
      2.5]; P = .03. Age is linked with inadequate provision of care in myeloma,
      particularly prognosis and first-line treatment. Compliance to guidelines seems
      to be related to OS taking into account the main prognostic factors. Future
      guidelines should stress the point that age and frailty need to be taken into
      account in myeloma care.

PMID- 28429428
TI  - Social media is essential for research engagement: AGAINST: Likes trumped by
      dislikes.

PMID- 28429427
TI  - The assessment of optical coherence tomographic parameters in subjects with a
      positive family history of glaucoma.
AB  - PURPOSE: The aim was to compare the optical coherence tomographic (OCT)
      parameters of subjects with and without a family history of glaucoma to determine
      whether positive family history has an impact on retinal nerve fibre layer and
      ganglion cell complex analyses. METHODS: Forty eyes of 40 normal subjects with a
      proven positive family history (first-degree relatives) for primary open angle
      glaucoma (POAG) (study group) and age-matched 40 eyes of 40 control subjects
      without a family history for glaucoma (control group) were enrolled. Retinal
      nerve fibre layer thickness and macular ganglion cell complex thickness were
      measured with spectral domain OCT and results were compared between both groups.
      RESULTS: In the study group, retinal nerve fibre layer thickness in all quadrants
      except the superior quadrant was a statistically significant decrease when
      compared to the control group (p = 0.707 for the superior quadrant, p < 0.05 for
      other retinal nerve fibre layer parameters; analysis of variance [ANOVA]).
      Furthermore, ganglion cell complex in all quadrants except the inferotemporal
      quadrant was a statistically significantly thinner in the study group, when
      compared with the controls (p = 0.196 for the inferotemporal quadrant, p < 0.05
      for ganglion cell complex parameters; ANOVA). CONCLUSIONS: In individuals who
      have a history of POAG in their first-degree relatives, OCT parameters including
      retinal nerve fibre layer and ganglion cell complex are significantly lower than
      the subjects without a family history. Retinal nerve fibre layer and ganglion
      cell complex thinning were detected in normal-looking discs. The importance of
      these findings remains uncertain. Prospective, controlled clinical trials with
      longer follow up are necessary to understand, whether or not those changes are an
      early indicator of glaucoma.

PMID- 28429430
TI  - A report from #BlueJC: Is surgical lymph node assessment necessary for women with
      mucinous ovarian cancer?

PMID- 28429431
TI  - Authors' reply re: Induction of labour with retrievable prostaglandin vaginal
      inserts: outcomes following retrieval due to an intrapartum adverse event.

PMID- 28429432
TI  - Improving the visibility of women's health.

PMID- 28429433
TI  - Author's reply re: Diagnostic work up for postmenopausal bleeding: a randomised
      controlled trial.

PMID- 28429434
TI  - Authors' reply re: Caesarean section rates and adverse neonatal outcomes after
      induction of labour versus expectant management in women with an unripe cervix: a
      secondary analysis of the HYPITAT and DIGITAT trials.

PMID- 28429435
TI  - Conservatism in Gynaecology.

PMID- 28429436
TI  - Are we steering full circle in our methods of labour induction?

PMID- 28429437
TI  - Re: Caesarean section rates and adverse neonatal outcomes after induction of
      labour versus expectant management in women with an unripe cervix: a secondary
      analysis of the HYPITAT and DIGITAT trials: Local cervical ripening, induction of
      labour, and caesarean section rate.

PMID- 28429438
TI  - Re: Induction of labour with retrievable prostaglandin vaginal inserts: outcomes
      following retrieval due to an intrapartum adverse event and Induction of labour:
      many choices, but still in search of the perfect protocol.

PMID- 28429439
TI  - Re: Diagnostic work up for postmenopausal bleeding: a randomised controlled
      trial: Evaluation of postmenopausal women by hysteroscopy.

PMID- 28429440
TI  - Authors' reply re: Diagnostic work up for postmenopausal bleeding: a randomised
      controlled trial.

PMID- 28429441
TI  - Social media is essential for research engagement: FOR: Facilitating stakeholder
      engagement is key!

PMID- 28429442
TI  - Re: Does tranexamic acid prevent postpartum haemorrhage? A systematic review of
      randomised controlled trials: A very welcome publication.

PMID- 28429443
TI  - A paradigm shift in the origin of ovarian cancer: the ovary is no longer to
      blame.

PMID- 28429445
TI  - Author's reply re re: Induction of labour: many choices, but still in search of
      the perfect protocol.

PMID- 28429444
TI  - Re: Induction of labour: many choices, but still in search of the perfect
      protocol.

PMID- 28429446
TI  - Puerperal sepsis: what has changed since Semmelweis's time.

PMID- 28429447
TI  - Using the realist perspective to link theory from qualitative evidence synthesis
      to quantitative studies: Broadening the matrix approach.
AB  - BACKGROUND: This study describes an approach for the use of a specific type of
      qualitative evidence synthesis in the matrix approach, a mixed studies reviewing
      method. The matrix approach compares quantitative and qualitative data on the
      review level by juxtaposing concrete recommendations from the qualitative
      evidence synthesis against interventions in primary quantitative studies.
      However, types of qualitative evidence syntheses that are associated with theory
      building generate theoretical models instead of recommendations. Therefore, the
      output from these types of qualitative evidence syntheses cannot directly be used
      for the matrix approach but requires transformation. This approach allows for the
      transformation of these types of output. METHOD: The approach enables the
      inference of moderation effects instead of direct effects from the theoretical
      model developed in a qualitative evidence synthesis. Recommendations for practice
      are formulated on the basis of interactional relations inferred from the
      qualitative evidence synthesis. In doing so, we apply the realist perspective to
      model variables from the qualitative evidence synthesis according to the context
      mechanism-outcome configuration. FINDINGS: A worked example shows that it is
      possible to identify recommendations from a theory-building qualitative evidence
      synthesis using the realist perspective. We created subsets of the interventions
      from primary quantitative studies based on whether they matched the
      recommendations or not and compared the weighted mean effect sizes of the
      subsets. The comparison shows a slight difference in effect sizes between the
      groups of studies. The study concludes that the approach enhances the
      applicability of the matrix approach.

PMID- 28429448
TI  - White matter microstructure variations contribute to neurological soft signs in
      healthy adults.
AB  - OBJECTIVE: Neurological soft signs (NSS) are core features of psychiatric
      disorders with significant neurodevelopmental origin. However, it is unclear
      whether NSS correlates are associated with neuropathological processes underlying
      the disease or if they are confounded by medication. Given that NSS are also
      present in healthy persons (HP), investigating HP could reveal NSS correlates,
      which are not biased by disease-specific processes or drug treatment. Therefore,
      we used a combination of diffusion MRI analysis tools to provide a framework of
      specific white matter (WM) microstructure variations underlying NSS in HP.
      METHOD: NSS of 59 HP were examined on the Heidelberg Scale and related to
      diffusion associated metrics. Using tract-based spatial statistics (TBSS), we
      studied WM variations in fractional anisotropy (FA) as well as radial (RD), axial
      (AD), and mean diffusivity (MD). Using graph analytics (clustering coefficient
      CC, local betweenness centrality -BC), we then explored DTI-derived structural
      network variations in regions identified by previous MRI studies on NSS. RESULTS:
      NSS scores were negatively associated with RD, AD and MD in corpus callosum,
      brainstem and cerebellum (P < 0.05, corr.). NSS scores were negatively associated
      with CC and BC of the pallidum, the superior parietal gyrus, the precentral
      sulcus, the insula, and the cingulate gyrus (P < 0.05, uncorr.). CONCLUSION: The
      present study supports the notion that WM microstructure variations in
      subcortical and cortical sensorimotor regions contribute to NSS expression in
      young HP. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28429449
TI  - Non-Pincer-Type Manganese Complexes as Efficient Catalysts for the Hydrogenation
      of Esters.
AB  - Catalytic hydrogenation of carboxylic acid esters is essential for the green
      production of pharmaceuticals, fragrances, and fine chemicals. Herein, we report
      the efficient hydrogenation of esters with manganese catalysts based on simple
      bidentate aminophosphine ligands. Monoligated Mn PN complexes are particularly
      active for the conversion of esters into the corresponding alcohols at Mn
      concentrations as low as 0.2 mol % in the presence of sub-stoichiometric amounts
      of KOt Bu base.

PMID- 28429450
TI  - On-bead MALDI-MS monitoring of solid-supported N-acyliminium ion reactions.

PMID- 28429451
TI  - A Strong cis-Effect in an Imidazole-Imidazolium-Substituted Alkene.
AB  - We report the first example of an alkene with two carbon-bound substituents
      (imidazole and imidazolium rings) where the Z-isomer has a greater thermodynamic
      stability than the E-isomer which persists in both the gas phase and in solution.
      Theoretical calculations, solution fluorescence spectroscopy and gas-phase ion
      mobility mass spectrometry studies confirm the preference for the Z-isomer, the
      stability of which is traced to a non-covalent interaction between the imidazole
      lone pair and the imidazolium ring.

PMID- 28429452
TI  - Real-world experience of the feasibility and tolerability of the 2/1 dosing
      schedule with sunitinib in the treatment of patients with advanced renal cell
      carcinoma in Australia.
AB  - AIM: Sunitinib is a first-line treatment option for metastatic renal cell
      carcinoma (mRCC) funded by the Australian Pharmaceutical Benefits Scheme.
      Toxicities are common with the standard schedule leading to alternative dosing
      schedules to be suggested. We reviewed Australian treatment practices to evaluate
      the safety and outcomes of patients on a 2 weeks on, 1 week off treatment
      schedule (2/1). METHODS: We performed a retrospective review of 63 patients with
      mRCC treated with first-line sunitinib on a 2/1 schedule at four Australian
      centers. RESULTS: Forty-six patients (73%) initiated sunitinib on the 2/1
      schedule whereas 17 (27%) switched from the 4/2 schedule due to toxicity. Three
      progressing on a 4/2 schedule tolerated up-titration of their dose with a
      clinical and radiological response on the 2/1 schedule. The median duration of
      treatment was 31.9 months; median duration of treatment on the 2/1 schedule in
      patients changing from 4/2 was 11.5 months. Few (6.3%) ceased due to toxicity.
      Median overall survival was 37.2 months. CONCLUSION: In this retrospective review
      of the 2/1 sunitinib schedule, time on treatment with clinical benefit exceeded
      the overall survival times seen in the phase III trials utilizing the 4/2
      schedule. Overall survival also exceeded that seen in these trials. Few patients
      ceased due to toxicity. The 2/1 schedule appears to be an acceptable schedule to
      use in selected patients with mRCC both at initiation of first-line treatment and
      in those intolerant to the 4/2 schedule.

PMID- 28429454
TI  - Scuba diving, patent foramen ovale and heart rhythm disturbances: The role of
      underwater Holter monitoring-Case report.
AB  - Patent foramen ovale (PFO) is thought to be a risk factor for decompression
      illness (DCI). Catheter-based closure procedure reduces the risk of DCI in
      selected scuba divers with PFO. Major complication of invasive approach are rare,
      minor, especially heart rhythm disturbances are reported relatively often. We
      describe a case of 41-year-old diver, who underwent PFO closure due to recurrent
      DCI events. Afterward, he experienced no DCI symptoms; however, he complained
      about feeling of the heart beating during a submersion. Arrhythmia should be
      considered as a life-threatening for scuba diver, thus we performed underwater
      ECG monitoring and exclude the arrhythmia.

PMID- 28429453
TI  - Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor
      growth in Neuroblastoma.
AB  - Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and
      other catecholamines by O-methylation. Tolcapone, a drug commonly used in the
      treatment of Parkinson's disease, is a potent inhibitor of COMT and previous
      studies indicate that Tolcapone increases the bioavailability of dopamine in
      cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB)
      cells in preclinical models by inhibition of COMT. Treating four established NB
      cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines
      with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with
      IncuCyte imaging and Western blotting indicating that cell death was due to
      caspase-3-mediated apoptosis. Tolcapone also increased ROS while simultaneously
      decreasing ATP-per-cell in NB cells. Additionally, COMT was inhibited by siRNA in
      NB cells and showed similar increases in apoptotic markers compared to Tolcapone.
      In vivo xenograft models displayed inhibition of tumor growth and a significant
      decrease in time-to-event in mice treated with Tolcapone compared to untreated
      mice. These results indicate that Tolcapone is cytotoxic to neuroblastoma cells
      and invite further studies into Tolcapone as a promising novel therapy for the
      treatment of neuroblastoma.

PMID- 28429455
TI  - Base-Controlled Completely Selective Linear or Branched Rhodium(I)-Catalyzed C-H
      ortho-Alkylation of Azines without Preactivation.
AB  - A [RhI ]/bisphosphine/base catalytic system for the ortho-selective C-H
      alkylation of azines by acrylates and acrylamides is reported. This catalytic
      system features an unprecedented complete linear or branched selectivity that is
      solely dependent on the catalytic base that is used. Complete branched
      selectivity is even achieved for ethyl methacrylate, which enables the
      introduction of a quaternary carbon center. Excellent functional group
      compatibility is demonstrated for both linear and branched alkylations. The
      operational simplicity and broad scope of this transformation allow for rapid
      access to functionalized azines of direct pharmaceutical and agrochemical
      relevance.

PMID- 28429456
TI  - The Term "Cornual Pregnancy" Should Be Abandoned.

PMID- 28429457
TI  - Surgical treatment and outcome of early invasive adenocarcinoma of the uterine
      cervix (FIGO stage IA1).
AB  - AIM: To investigate the surgical outcome of FIGO stage IA1 cervical
      adenocarcinoma. METHODS: Between 2005 and 2011, 12 patients from Kyushu
      University Hospital had cervical adenocarcinoma, with a tumor depth of less than
      3 mm and a horizontal width of less than 7 mm (FIGO stage IA1), diagnosed by
      cervical conization. All patients underwent simple hysterectomy or simple
      trachelectomy with pelvic lymphadenectomy. RESULTS: The mean patient age was 34
      years (range, 26-70 years). The median follow-up period was 70.5 months (range,
      26-99 months). No pelvic lymph-node metastasis was seen, and no patient
      experienced disease recurrence. CONCLUSION: Early invasive cervical
      adenocarcinoma with a depth of invasion of 3 mm or less and a horizontal spread
      of 7 mm or less has little potential for nodal metastasis or recurrence.
      Therefore, simple hysterectomy or trachelectomy, without lymphadenectomy, might
      be an alternative treatment option for stage IA1 cervical adenocarcinoma.

PMID- 28429458
TI  - Genomic evidence for population-specific responses to co-evolving parasites in a
      New Zealand freshwater snail.
AB  - Reciprocal co-evolving interactions between hosts and parasites are a primary
      source of strong selection that can promote rapid and often population- or
      genotype-specific evolutionary change. These host-parasite interactions are also
      a major source of disease. Despite their importance, very little is known about
      the genomic basis of co-evolving host-parasite interactions in natural
      populations, especially in animals. Here, we use gene expression and sequence
      evolution approaches to take critical steps towards characterizing the genomic
      basis of interactions between the freshwater snail Potamopyrgus antipodarum and
      its co-evolving sterilizing trematode parasite, Microphallus sp., a textbook
      example of natural coevolution. We found that Microphallus-infected P.
      antipodarum exhibit systematic downregulation of genes relative to uninfected P.
      antipodarum. The specific genes involved in parasite response differ markedly
      across lakes, consistent with a scenario where population-level co-evolution is
      leading to population-specific host-parasite interactions and evolutionary
      trajectories. We also used an FST -based approach to identify a set of loci that
      represent promising candidates for targets of parasite-mediated selection across
      lakes as well as within each lake population. These results constitute the first
      genomic evidence for population-specific responses to co-evolving infection in
      the P. antipodarum-Microphallus interaction and provide new insights into the
      genomic basis of co-evolutionary interactions in nature.

PMID- 28429459
TI  - Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors
      for acute stroke.
AB  - BACKGROUND: Nitric oxide (NO) has multiple effects that may be beneficial in
      acute stroke, including lowering blood pressure, and promoting reperfusion and
      cytoprotection. Some forms of nitric oxide synthase inhibition (NOS-I) may also
      be beneficial. However, high concentrations of NO are likely to be toxic to brain
      tissue. This is an update of a Cochrane review first published in 1998, and last
      updated in 2002. OBJECTIVES: To assess the safety and efficacy of NO donors, L
      arginine, and NOS-I in people with acute stroke. SEARCH METHODS: We searched the
      Cochrane Stroke Group Trials Register (last searched 6 February 2017), MEDLINE
      (1966 to June 2016), Embase (1980 to June 2016), ISI Science Citation Indexes
      (1981 to June 2016), Stroke Trials Registry (searched June 2016), International
      Standard Randomised Controlled Trial Number (ISRCTN) (searched June 2016),
      Clinical Trials registry (searched June 2016), and International Clinical Trials
      Registry Platform (ICTRP) (searched June 2016). Previously, we had contacted drug
      companies and researchers in the field. SELECTION CRITERIA: Randomised controlled
      trials comparing nitric oxide donors, L-arginine, or NOS-I versus placebo or open
      control in people within one week of onset of confirmed stroke. DATA COLLECTION
      AND ANALYSIS: Two review authors independently applied the inclusion criteria,
      assessed trial quality and risk of bias, and extracted data. The review authors
      cross-checked data and resolved issues through discussion. We obtained published
      and unpublished data, as available. Data were reported as mean difference (MD) or
      odds ratio (OR) with 95% confidence intervals (CI). MAIN RESULTS: We included
      five completed trials, involving 4197 participants; all tested transdermal
      glyceryl trinitrate (GTN), an NO donor. The assessed risk of bias was low across
      the included studies; one study was double-blind, one open-label and three were
      single-blind. All included studies had blinded outcome assessment. Overall, GTN
      did not improve the primary outcome of death or dependency at the end of trial
      (modified Rankin Scale (mRS) > 2, OR 0.97, 95% CI 0.86 to 1.10, 4195
      participants, high-quality evidence). GTN did not improve secondary outcomes,
      including death (OR 0.78, 95% CI 0.40 to 1.50) and quality of life (MD -0.01, 95%
      CI -0.17 to 0.15) at the end of trial overall (high-quality evidence).
      Systolic/diastolic blood pressure (BP) was lower in people treated with GTN (MD 
      7.2 mmHg (95% CI -8.6 to -5.9) and MD -3.3 (95% CI -4.2 to -2.5) respectively)
      and heart rate was higher (MD 2.0 beats per minute (95% CI 1.1 to 2.9)). Headache
      was more common in those randomised to GTN (OR 2.37, 95% CI 1.55 to 3.62). We did
      not find any trials assessing other nitrates, L-arginine, or NOS-I. AUTHORS'
      CONCLUSIONS: There is currently insufficient evidence to recommend the use of NO
      donors, L-arginine or NOS-I in acute stroke, and only one drug (GTN) has been
      assessed. In people with acute stroke, GTN reduces blood pressure, increases
      heart rate and headache, but does not alter clinical outcome (all based on high
      quality evidence).

PMID- 28429460
TI  - Automated T-wave analysis can differentiate acquired QT prolongation from
      congenital long QT syndrome.
AB  - BACKGROUND: Prolongation of the QT on the surface electrocardiogram can be due to
      either genetic or acquired causes. Distinguishing congenital long QT syndrome
      (LQTS) from acquired QT prolongation has important prognostic and management
      implications. We aimed to investigate if quantitative T-wave analysis could
      provide a tool for the physician to differentiate between congenital and acquired
      QT prolongation. METHODS: Patients were identified through an institution-wide
      computer-based QT screening system which alerts the physician if the QTc >= 500
      ms. ECGs were retrospectively analyzed with an automated T-wave analysis program.
      Congenital LQTS was compared in a 1:3 ratio to those with an identified acquired
      etiology for QT prolongation (electrolyte abnormality and/or prescription of
      known QT prolongation medications). Linear discriminant analysis was performed
      using 10-fold cross-validation to statistically test the selected features.
      RESULTS: The 12-lead ECG of 38 patients with congenital LQTS and 114 patients
      with drug-induced and/or electrolyte-mediated QT prolongation were analyzed. In
      lead V5 , patients with acquired QT prolongation had a shallower T wave right
      slope (-2,322 vs. -3,593 mV/s), greater T-peak-Tend interval (109 vs. 92 ms), and
      smaller T wave center of gravity on the x axis (290 ms vs. 310 ms; p < .001).
      These features could distinguish congenital from acquired causes in 77% of cases
      (sensitivity 90%, specificity 58%). CONCLUSION: T-wave morphological analysis on
      lead V5 of the surface ECG could successfully differentiate congenital from
      acquired causes of QT prolongation.

PMID- 28429461
TI  - Deodorization of Arthrospira platensis biomass for further scale-up food
      applications.
AB  - BACKGROUND: Given the importance of A. platensis as a potential food protein
      source, we describe an affordable deodorization process that does not
      significantly affect the nutritional value of algae biomass. RESULTS: Ethanol,
      acetone or hexane were used to deodorize algae biomass and then to identify the
      profile of volatile compounds associated with its distinctive odor. Sensorial
      characteristics were improved in the biomass cake after the proposed solvent
      extraction. Panelists identified the ethanolic extract with the most pronounced
      algae-related odor. Gas chromatography-mass spectrometry analysis showed that a
      mixture of 20 different compounds derived from fatty acids and amino acids
      contributed to the characteristic smell of A. platensis biomass. The results of
      the present study show that the ethanol solvent-free A. platensis biomass
      contained > 600 g kg-1 protein, < 10 g kg-1  crude fat and > 65% in vitro protein
      digestibility, similar to the original biomass. The Fourier transform infrared
      spectroscopy secondary protein structure was comparable among samples, indicating
      that the only change after ethanol extraction was a reduction of the algae smell.
      CONCLUSION: The various extraction procedures investigated in the present study
      were effective in deodorizing the algae biomass. The most effective protocol was
      the removal of odoriferous compounds with ethanol. This particular procedure
      yielded an algae biomass with an improved sensorial traits. The results of the
      present study should help with the identification of odoriferous compounds
      derived from fatty acids, pigments and proteins associated with A. platensis. (c)
      2017 Society of Chemical Industry.

PMID- 28429462
TI  - Kinship, nomadism, and humanitarian aid among Somalis in Ethiopia.
AB  - This paper draws on extended ethnographic and health policy research in eastern
      Ethiopia to reconsider kinship and nomadism among Somalis, as both of these
      cultural features transform in the contexts of recurrent humanitarian crises and
      episodic relief operations. The emergence and importance of new patterns of
      travel and migration among Somalis in Ethiopia reveal significant changes in the
      configurations and enactments of Somali kinship, on which many Somalis' mobility
      depends. Conversely, an analysis of Somalis' dynamic sub-clan groupings and
      geographically dispersed kinship networks also highlights emergent patterns of
      mobility and migration that enable access to training opportunities and
      employment with relief organisations, as well as to distributions of humanitarian
      aid. Based on these findings, this paper argues that kinship and nomadism-both
      long central to Somalis' identities in Ethiopia-remain interdependent, coevolved,
      and key to their resilience and livelihoods in the face of recurrent crises and
      intermittent humanitarian responses.

PMID- 28429463
TI  - Global Mapping of Protein-Lipid Interactions by Using Modified Choline-Containing
      Phospholipids Metabolically Synthesized in Live Cells.
AB  - The protein-lipid interaction is an essential metabolic process that mediates
      cellular signaling and functions. Existing strategies for large-scale mapping
      studies of the protein-lipid interaction fall short in their incompatibility with
      metabolic incorporation or inability to remove unwanted interferences from
      lipidated proteins. By incorporating an alkyne-containing choline head group and
      a diazirine-modified fatty acid simultaneously into choline-containing
      phospholipids synthesized from live mammalian cells, protein-phospholipid
      interactions have been successfully imaged in live cells. Subsequent in situ
      profiling of the modified Cho phospholipid-crosslinked proteins followed by
      quantitative proteomics allowed identification of several hundred putative
      phospholipid-interacting proteins, some of which were further validated.

PMID- 28429465
TI  - Rapid Access to Nitrogenous Heterobicycles via RhIII -Catalyzed Isomerization
      from Alkynes to Allenes.
AB  - We show that N-alkynylnitrones are efficiently converted to nitrogenous
      heterobicyclic compounds with a nitrogen atom at the bridgehead position by using
      a RhIII -catalyst. Our mechanistic studies suggest that the reaction proceeds via
      an allene intermediate, which is generated in situ through RhIII -catalyzed
      isomerization of the alkyne group.

PMID- 28429464
TI  - Inflammatory features of frontal fibrosing alopecia.
AB  - INTRODUCTION: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia
      typically occurring in postmenopausal women. The etiology and pathophysiology of
      FFA is poorly understood but thought to be immune mediated. This study aims to
      further explore the extent of fibrosis and the inflammatory microenvironment by
      characterizing Langerhans cells (LCs), helper T cells, cytotoxic T cells and B
      cells near hair follicles in FFA. METHODS: Eleven paraffin-embedded tissues from
      patients with a clinical and histopathologic diagnosis of FFA were selected for
      immunohistochemical studies using CD3, CD4, CD8, CD1a and CD20. The lymphocytes
      and LCs were counted around involved follicles. The CD4/CD8 T-lymphocyte ratios
      were calculated and compared to the CD4/CD8 T-lymphocyte ratios in uninvolved
      areas. RESULTS: On histopathologic review, at least 35% of follicles in each case
      were affected by the disease with concentric perifollicular fibrosis and a
      perifollicular lichenoid lymphocytic infiltrate around the infundibuloisthmic
      portion of the hair follicle. There was an increase of perifollicular LCs (mean
      of 18, SD of 5.5) and intrafollicular LCs (mean of 14, SD of 4.3) in involved
      follicles compared to uninvolved follicles (P < .0001). The involved follicles
      also showed a relative decrease in the CD4/CD8 ratio indicating increased numbers
      of CD8+ T cells; a finding distinct from the CD4-predominant population in
      uninvolved follicles (P < .0001). CONCLUSION: The inflammatory features of FFA
      show a CD8-biased T-cell infiltrate with increased numbers of LCs in the
      infundibuloisthmic region. The increased LCs may represent an aberrant immune
      reaction promoting a CD8+ T-cell response.

PMID- 28429466
TI  - Psychosocial outcomes in active treatment through survivorship.
AB  - OBJECTIVE: The objective of the study is to understand potential differences in
      psychosocial outcomes from active treatment to survivorship. METHODS: Using the
      Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement
      (n = 1360), we examined and compared psychosocial outcomes among respondents in
      active treatment with survivors by year(s) since treatment ended. Survey-weighted
      regression models were used to test associations between year(s) since treatment
      and depressive symptoms (Patient Health Questionnaire-2), psychological distress
      (K6), and cancer-specific worry related to recurrence. RESULTS: Unadjusted
      estimates showed no significant differences in depressive symptoms or
      psychological distress between those in active treatment and cancer survivors at
      any time posttreatment. In contrast, the prevalence of cancer-specific worry was
      lowest among survivors more than 5 years since treatment (10%), slightly higher
      among those with less than 1 year since treatment (15%), and highest among those
      in active treatment (32%). In models controlled for sociodemographic and health
      related covariates, the year(s) since treatment ended was inversely associated
      with the odds of cancer-specific worry but was not associated with depressive
      symptoms or psychological distress. CONCLUSIONS: In this population-based sample,
      worry about cancer recurrence may diminish with years since treatment ended,
      while depressive symptoms and distress are persistent across the trajectory.
      These findings highlight unmet psychosocial needs among cancer survivors and
      demonstrate the importance of targeted interventions across the survivorship
      continuum.

PMID- 28429467
TI  - Conditional random slope: A new approach for estimating individual child growth
      velocity in epidemiological research.
AB  - OBJECTIVES: Conditioning child growth measures on baseline accounts for
      regression to the mean (RTM). Here, we present the "conditional random slope"
      (CRS) model, based on a linear-mixed effects model that incorporates a baseline
      time interaction term that can accommodate multiple data points for a child while
      also directly accounting for RTM. METHODS: In two birth cohorts, we applied five
      approaches to estimate child growth velocities from 0 to 12 months to assess the
      effect of increasing data density (number of measures per child) on the magnitude
      of RTM of unconditional estimates, and the correlation and concordance between
      the CRS and four alternative metrics. Further, we demonstrated the differential
      effect of the choice of velocity metric on the magnitude of the association
      between infant growth and stunting at 2 years. RESULTS: RTM was minimally
      attenuated by increasing data density for unconditional growth modeling
      approaches. CRS and classical conditional models gave nearly identical estimates
      with two measures per child. Compared to the CRS estimates, unconditional metrics
      had moderate correlation (r = 0.65-0.91), but poor agreement in the
      classification of infants with relatively slow growth (kappa = 0.38-0.78).
      Estimates of the velocity-stunting association were the same for CRS and
      classical conditional models but differed substantially between conditional
      versus unconditional metrics. CONCLUSION: The CRS can leverage the flexibility of
      linear mixed models while addressing RTM in longitudinal analyses.

PMID- 28429468
TI  - Decision-making in obesity without eating disorders: a systematic review and meta
      analysis of Iowa gambling task performances.
AB  - BACKGROUND: There is evidence that obesity is associated with impairments in
      executive functions, such as deficits in decision-making, planning or problem
      solving, which might interfere with weight loss in obese individuals. We
      performed a systematic review and meta-analysis of decision-making abilities, as
      measured with the Iowa gambling task (IGT), in obesity without eating disorders.
      METHODS: A systematic search was conducted to identify studies comparing IGT
      performances between groups of obese patients without eating disorders and groups
      of healthy control groups. The standardized mean differences were calculated for
      the total IGT scores and for the course of IGT scores. Meta-regression analyses
      were performed to explore the influence of clinical variables on standardized
      mean differences. RESULTS: Total IGT scores were significantly lower in obese
      patients compared with normal-weight healthy controls. IGT performances did not
      differ between groups for the first trials of the task. Significant effect sizes
      for the last trials of the task were subjected to a high degree of heterogeneity.
      CONCLUSION: Risky decision-making is impaired in obesity. The clinical importance
      of non-food-related decision-making impairments remains to be assessed especially
      in terms of consequences in daily life or the achievement of weight loss. This
      meta-analysis has been registered in the Prospero database (CRD42016037533).

PMID- 28429469
TI  - High body mass and kidney dysfunction relate to worse nerve function, even in
      adults without neuropathy.
AB  - Polyneuropathy is a prevalent and disabling disorder. Despite extensive
      evaluation, the cause often remains unknown. Factors that predispose for the
      development of polyneuropathy need to be identified. We investigated the effect
      of anthropometric and metabolic factors on peripheral nerve function in 908
      participants of the population-based Rotterdam Study without any symptoms or
      signs of polyneuropathy. Participants underwent nerve conduction studies of the
      sural and peroneal nerve. Data on age, height, weight, waist circumference,
      diabetes, lipid levels, hypertension, and kidney function were collected.
      Regression analyses were used to investigate determinants of nerve action
      potential amplitudes. The frequency of abnormal sural sensory nerve action
      potential (SNAP) amplitudes increased with age from 1% under 60 years to 23% over
      80 years. Similarly, the frequency of abnormal peroneal nerve compound motor
      action potential (CMAP) amplitudes increased from 4% to 13%. High weight and body
      mass index were independently associated with reduced sural SNAP amplitudes and
      peroneal CMAP amplitudes. Participants with hypertension and kidney dysfunction
      were more likely to have abnormal sural SNAP amplitudes. Older age, high weight,
      hypertension, and moderate kidney dysfunction might thus lead to peripheral nerve
      dysfunction in persons yet without symptoms or signs of polyneuropathy.

PMID- 28429470
TI  - Meta-analysis combining parallel and cross-over trials with random effects.
AB  - Meta-analysis can necessitate the combination of parallel and cross-over trial
      designs. Because of the differences in the trial designs and potential biases
      notably associated with the crossover trials, one often combines trials of the
      same designs only, which decreases the power of the meta-analysis. To combine
      results of clinical trials from parallel and cross-over designs, we extend the
      method proposed in an accompanying study to account for random effects. We
      propose here a hierarchical mixed model allowing the combination of the 2 types
      of trial designs and accounting for additional covariates where random effects
      can be introduced to account for heterogeneity in trial, treatment effect, and
      interactions. We introduce a multilevel model and a Bayesian hierarchical model
      for combined trial design meta-analysis. The analysis of the models by restricted
      iterative generalised least square and Monte Carlo Markov Chain is presented.
      Methods are compared in a combined design meta-analysis model on salt reduction.
      Both models and their respective advantages in the perspective of meta-analysis
      are discussed. However, the access to the trial data, in particular sequence and
      period data in cross-over trials, remains a major limitation to the meta-analytic
      combination of trial designs.

PMID- 28429471
TI  - Formation of Silver Nanoparticles by Electron Transfer in Peptides and c
      Cytochromes.
AB  - The reduction of Ag+ ions to Ag0 atoms is a highly endergonic reaction step, only
      the aggregation to Agn clusters leads to an exergonic process. These elementary
      chemical reactions play a decisive role if Ag nanoparticles (AgNPs) are generated
      by electron transfer (ET) reactions to Ag+ ions. We studied the formation of
      AgNPs in peptides by photoinduced ET, and in c-cytochromes by ET from their Fe2+
      /hemes. Our earlier photoinduced experiments in peptides had demonstrated that
      histidine prevents AgNP formation. We have now observed that AgNPs can be easily
      synthesized with less-efficient Ag+ -binding amino acids, and the rate increases
      in the order lysine<asparagine<aspartate<serine. The ability of Fe2+ /hemes of c
      cytochromes to reduce Ag+ to AgNPs was studied in an enzymatic experiment and
      with living bacteria Geobacter sulfurreducens (Gs).

PMID- 28429472
TI  - Transoral orthodromic temporalis muscle transfer technique for the paralysed
      midface: Our learning curve experience from the first 10 cases.

PMID- 28429473
TI  - Surgery for limited-stage small-cell lung cancer.
AB  - BACKGROUND: Current treatment guidelines for limited-stage small-cell lung cancer
      (SCLC) recommend concomitant platinum-based chemo-radiotherapy plus prophylactic
      cranial irradiation, based on the premise that SCLC disseminates early, and is
      chemosensitive. However, although there is usually a favourable initial response,
      relapse is common and the cure rate for limited-stage SCLC remains relatively
      poor. Some recent clinical practice guidelines have recommended surgery for stage
      1 (limited) SCLC followed by adjuvant chemotherapy, but this recommendation is
      largely based on the findings of observational studies. OBJECTIVES: To determine
      whether, in patients with limited-stage SCLC, surgical resection of cancer
      improves overall survival and treatment-related deaths compared with radiotherapy
      or chemotherapy, or a combination of radiotherapy and chemotherapy, or best
      supportive care. SEARCH METHODS: We performed searches on CENTRAL, MEDLINE,
      Embase, CINAHL, and Web of Science up to 11 January 2017. We handsearched review
      articles, clinical trial registries, and reference lists of retrieved articles.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) with adults
      diagnosed with limited-stage SCLC, confirmed by cytology or histology, and
      radiological assessment, considered medically suitable for resection and radical
      radiotherapy, which randomised participants to surgery versus any other
      intervention. DATA COLLECTION AND ANALYSIS: We imported studies identified by the
      search into a reference manager database. We retrieved the full-text version of
      relevant studies, and two review authors independently extracted data. The
      primary outcome measures were overall survival and treatment-related deaths; and
      secondary outcome measures included loco-regional progression, quality of life,
      and adverse events. MAIN RESULTS: We included three trials with 330 participants.
      We judged the quality of the evidence as very low for all the outcomes. The
      quality of the data was limited by the lack of complete outcome reporting,
      unclear risk of bias in the methods in which the studies were conducted, and the
      age of the studies (> 20 years). The methods of cancer staging and types of
      surgical procedures, which do not reflect current practice, reduced our
      confidence in the estimation of the effect.Two studies compared surgery to
      radiation therapy, and in one study chemotherapy was administered to both arms.
      One study administered initial chemotherapy, then responders were randomised to
      surgery versus control; following, both groups underwent chest and whole brain
      irradiation.Due to the clinical heterogeneity of the trials, we were unable to
      pool results for meta-analysis.All three studies reported overall survival. One
      study reported a mean overall survival of 199 days in the surgical arm, compared
      to 300 days in the radiotherapy arm (P = 0.04). One study reported overall
      survival as 4% in the surgical arm, compared to 10% in the radiotherapy arm at
      two years. Conversely, one study reported overall survival at two years as 52% in
      the surgical arm, compared to 18% in the radiotherapy arm. However this
      difference was not statistically significant (P = 0.12).One study reported early
      postoperative mortality as 7% for the surgical arm, compared to 0% mortality in
      the radiotherapy arm. One study reported the difference in mean degree of
      dyspnoea as -1.2 comparing surgical intervention to radiotherapy, indicating that
      participants undergoing radiotherapy are likely to experience more dyspnoea. This
      was measured using a non-validated scale. AUTHORS' CONCLUSIONS: Evidence from
      currently available RCTs does not support a role for surgical resection in the
      management of limited-stage small-cell lung cancer; however our conclusions are
      limited by the quality of the available evidence and the lack of contemporary
      data. The results of the trials included in this review may not be generalisable
      to patients with clinical stage 1 small-cell lung cancer carefully staged using
      contemporary staging methods. Although some guidelines currently recommend
      surgical resection in clinical stage 1 small-cell lung cancer, prospective
      randomised controlled trials are needed to determine if there is any benefit in
      terms of short- and long-term mortality and quality of life compared with chemo
      radiotherapy alone.

PMID- 28429474
TI  - The influence of Glu-1 and Glu-3 loci on dough rheology and bread-making
      properties in wheat (Triticum aestivum L.) doubled haploid lines.
AB  - BACKGROUND: The major determinants of wheat quality are Glu-1 and Glu-3 glutenin
      loci and environmental factors. Additive effects of alleles at the Glu-1 and Glu
      3 loci, as well as their interactions, were evaluated for dough rheology and
      baking properties in four groups of wheat doubled haploid lines differing in high
      and low-molecular-weight glutenin composition. RESULTS: Flour quality, Reomixer
      (Reologica Instruments, Lund, Sweden), dough extension, Farinograph (Brabender
      GmbH, Duisburg, Germany) and baking parameters were determined. Groups of lines
      with the alleles Glu-A3b and Glu-B3d were characterized by higher values of dough
      and baking parameters compared to those with the Glu-A3e and Glu-B3a alleles.
      Effects of interactions between allelic variants at the Glu-1 and Glu-3 loci on
      Reomixer parameters, dough extension tests and baking parameters were
      significant, although additive effects of individual alleles were not always
      significant. CONCLUSION: The allelic variants at Glu-B3 had a much greater effect
      on dough rheological parameters than the variants at Glu-A3 or Glu-D3 loci. The
      effect of allelic variations at the Glu-D3 loci on rheological parameters and
      bread-making quality was non-significant, whereas their interactions with a
      majority of alleles at the other Glu-1 * Glu-3 loci were significant. (c) 2017
      Society of Chemical Industry.

PMID- 28429475
TI  - Common Carotid Artery Sonography Versus Transthoracic Echocardiography for
      Cardiac Output Measurements in Intensive Care Unit Patients.
AB  - OBJECTIVES: This study was designed to test the effectiveness of common carotid
      artery sonography in comparison with transthoracic echocardiography (TTE) for
      cardiac output measurements to provide an easier alternative for cardiac output
      monitoring in the intensive care unit. METHODS: This study included 148 patients
      who had common carotid artery Doppler examinations and TTE performed within 8
      hours of each other, and the cardiac output measurement results were compared
      with each other. RESULTS: The mean age of the participants +/- SD was 56.8 +/-
      16.2 years, with male patients composing 54.7% of the cohort. There was no
      significant difference in carotid and TTE cardiac output between different sexes,
      age groups, patients with and without mechanical ventilation, and primary
      indication groups. The overall intraclass correlation coefficient between the
      carotid and TTE cardiac output was 0.537. In patients with septic shock, multiple
      trauma, and respiratory failure, the intraclass correlation coefficients between
      TTE and carotid cardiac output were 0.241, 0.061, and 0.095, respectively.
      CONCLUSIONS: Carotid cardiac output shows moderate agreement with TTE cardiac
      output; thus, its use may be considered as an alternative for estimating cardiac
      output in emergencies and when TTE cardiac output is unobtainable. However, in
      patients with septic shock, multiple trauma, and respiratory failure, the use of
      carotid cardiac output is not recommended.

PMID- 28429476
TI  - Periodontal disease and the special needs patient.
AB  - Individuals with special needs are at more risk of dental disease, including
      periodontal diseases, and have a greater prevalence and incidence of periodontal
      diseases than the rest of the population. Genetic or medical conditions, and/or
      the use of prescription medication or recreational substances, may further
      increase the risk for susceptibility to periodontal disease. The success of
      preventing or controlling periodontal diseases amongst this group of patients has
      not been established. Even those individuals who access regular and comprehensive
      dental care appear to develop periodontal diseases as they age, and this
      development occurs at a rate comparable to the natural history of the disease.
      The reasons behind the lack of success of interventions in reducing the incidence
      of periodontal diseases are complex and part of the lack of success may relate to
      the professional challenges in treating individuals with special needs.

PMID- 28429477
TI  - The emerging role of maxillofacial radiology in the diagnosis and management of
      patients with complex periodontitis.
AB  - Contemporary periodontal therapy has evolved to become more interdisciplinary and
      increasingly involves more complex treatments, including bone and soft-tissue
      regenerative procedures. Therapeutic options require an imaging modality or
      combination of techniques that are capable of providing a diagnostic osseous
      baseline and facilitating quantification of smaller increments of bony change,
      both loss and additive, which are comparable over time. Intra-oral and panoramic
      radiography are the modalities most commonly used to identify the location,
      quantify the amount and the pattern of alveolar bone loss and determine response
      to therapy. Cone-beam computed tomography imaging offers specific advantages for
      periodontal diagnosis in that three-dimensional images of dental and alveolar
      bone structures can be rendered with accuracy. Cone-beam computed tomography has
      been shown to be clinically efficacious in demonstrating localized defects, such
      as furcation involvement and intrabony vertical and buccal/lingual defects, and
      in assessing the effects of regenerative therapy. In these situations, limited
      field-of-view, high-resolution protocols are indicated.

PMID- 28429478
TI  - The nexus between periodontics and oral pathology.
AB  - A wide variety of lesions may arise from the oral mucosa, fibrous connective
      tissue, bone and cementum of the periodontium. The commonest pathology occurs as
      a result of bacterial infection and is very well known to dentists and
      periodontists, but rarer conditions present as gingival pathology. The
      pathogenesis of these conditions ranges from genetic to traumatic to
      immunological to neoplastic, and includes benign, malignant and metastatic
      lesions. This paper outlines some of these conditions and describes how the
      periodontist and oral pathologist can work together using a framework, and how
      with careful consideration of the clinical features and the use of appropriate
      special tests, including obtaining an adequate tissue specimen, a timely and
      accurate diagnosis can be obtained.

PMID- 28429479
TI  - Dental geriatrics and periodontitis.
AB  - The present literature review is focused on two main areas: (i) periodontal
      conditions in older individuals; and (ii) the scientific data available on
      periodontal treatment outcomes in individuals >= 75 years of age. The population
      of older people is increasing but the data on periodontal therapies and their
      efficacy in this population are limited and need to be carefully reviewed.
      Although life expectancy has increased, this does not mean that older people are
      medically healthy. Several chronic systemic diseases are associated with
      periodontitis, and the prevalence of most chronic diseases increases with age.
      Furthermore, older people are challenged by impaired immunity (immune senescence)
      with a decline in the numbers of naive T-cells in peripheral blood and lymphoid
      tissues. The most frequent significant correlates with successful ageing include
      not smoking and the absence of disability, arthritis and diabetes mellitus.
      Periodontal diseases in older individuals may have specific features that are not
      consistent with periodontal diseases. In this respect, data suggest that gingival
      lesions in older individuals develop differently from gingival lesions in younger
      adults. The progression of periodontitis may be slower in older individuals, and
      older individuals with periodontitis may benefit from more conservative treatment
      approaches. Diagnostic criteria used for the assessment and diagnosis of
      periodontitis in younger adults may not be fully applicable in older individuals.
      In summary, declining health, perception of treatment needs, dietary changes,
      comorbidity with other diseases and immune senescence are challenging factors to
      clinicians and researchers, in terms of therapies and in understanding
      periodontitis etiology in older individuals.

PMID- 28429480
TI  - Surgical management in dentistry: the interdisciplinary relationship between
      periodontology and oral and maxillofacial surgery.
AB  - Surgical procedures of the oral cavity can be performed by a number of dental
      specialists and clinicians. Because of the limited number of surgical procedures
      that can be performed inside the oral cavity, the boundaries between specialties
      may become indistinct and lead to confusion for general dentists in terms of
      patient referrals. In this article, what the two surgical specialties of
      dentistry (i.e. periodontology and oral and maxillofacial surgery) have to offer
      is highlighted, together with clinical examples to illustrate the
      interdisciplinary relationship between them.

PMID- 28429481
TI  - Interdisciplinary interface between fixed prosthodontics and periodontics.
AB  - Although periodontal factors do not usually have a direct effect on the survival
      of a fixed prosthesis, harmony between the prosthesis and the periodontium is
      critical otherwise esthetics, the longevity of the prosthesis and the
      periodontium will be compromised. A close interdisciplinary relationship between
      periodontics and prosthodontics is therefore necessary to avoid an unsatisfactory
      treatment outcome, requiring extensive and expensive retreatment. The design of
      the prosthesis, the number and quality of the abutment teeth, the preparation and
      the pontic, the occlusion and the material need to be considered when planning
      prosthodontic treatment. The location of the preparation margin and the contour
      and emergence profile of the prosthesis will influence the response of the
      gingival tissues to the prosthesis. Pontic design and cleansibility also
      contribute to the response of the gingival tissues as well as to the clinical and
      esthetic outcome. Even an optimal pontic design will not prevent inflammation of
      the mucosa adjacent to the pontic if pontic hygiene is not maintained by removal
      of plaque. Case selection and the patients' ability to carry out adequate oral
      hygiene are therefore essential for longevity of the prosthesis, and regular
      reviews provide an opportunity for early detection and treatment of failures.

PMID- 28429482
TI  - The periodontal restorative interface: esthetic considerations.
AB  - Esthetic considerations are a significant contributing factor in the management
      of prosthodontic cases and an interdisciplinary approach is often necessary to
      achieve an optimal result. The visible soft-tissue architecture plays a key role
      in developing an esthetic smile. Furthermore, an understanding of the
      relationship between the restorative margin and the gingiva is important for long
      term stability of the result. The gingival architecture and gingival health are
      important for ensuring optimal esthetics following prosthodontic work and close
      attention to both soft and hard tissues around the teeth, before, during and
      after restorative procedures, will greatly improve the likelihood of a successful
      outcome. Moreover, knowing the options available in periodontal plastic surgery
      is important in esthetic dentistry today. The relevant literature related to
      restorative and surgical procedures when performing esthetic dentistry are
      reviewed in this article, and different approaches are illustrated with
      appropriate cases to explain the treatment approach that was utilized to improve
      the esthetic appearance of the case.

PMID- 28429483
TI  - Management of periodontal health in children: pediatric dentistry and
      periodontology interface.
AB  - The oral health of children and adolescents mirrors their general health. Because
      oral health care is often delivered in isolation from general health care, oral
      signs and symptoms do not always alert practitioners to their significance beyond
      the mouth. An important example of this is the association of a higher risk of
      dental caries and periodontal disease in children and adolescents with
      overweight, obesity and prediabetic conditions. Oral-health practitioners need to
      consider the health conditions that their patients may have. This will aid in
      diagnosis and alert the practitioner to oral conditions that may not resolve
      without general health-care intervention also. This paper reviews the more common
      oral conditions involving periodontal health in children and adolescents, and
      discusses the diagnosis of these conditions, potential associated health problems
      and the roles of pediatric dentistry and periodontology in the management of
      these conditions with the goal of children entering adulthood with healthy
      dentitions.

PMID- 28429484
TI  - Interaction between endodontics and periodontics.
AB  - Endodontic-periodontal lesions present challenges to the clinician regarding
      diagnosis, treatment planning and prognosis. Etiologic factors, such as bacteria
      and viruses, as well as contributing factors, such as trauma, root resorptions,
      perforations, cracks and dental malformations, play an important role in the
      development and progression of such lesions. Treatment and prognosis of
      endodontic-periodontal lesions vary, depending on the etiology, pathogenesis and
      correct diagnosis of each specific condition. This chapter will appraise the
      interrelationship between endodontic and periodontal lesions and provide
      biological and clinical evidence for diagnosis, prognosis and decision-making in
      the treatment of these conditions.

PMID- 28429485
TI  - The place of periodontal examination and referral in general medicine.
AB  - In many countries, dental services, unlike other health-care services, are not
      covered by the principle of universal access. It is only in the last couple of
      decades that there has been a greater interaction between medicine and dentistry.
      Various health-care systems worldwide may provide public dental services to the
      young and the disadvantaged, but few provide access to all. Public policy does
      not appear to appreciate the vast economic, health and social implications of
      poor oral health on the overall health of an individual. Recognizing and acting
      on the interrelatedness between oral health and overall health helps to protect
      patients from pathological diseases, such as infective endocarditis, suboptimal
      glycemic control and deterioration in renal function. This review article
      examines some of the medical conditions to which patients are predisposed as a
      result of poor dental care. Additionally, the paper provides some real-life case
      examples to support this hypothesis, reinforces the importance of a strong
      relationship that needs to be embedded between the dentist and the physician and
      finally provides some suggestions for a multidisciplinary approach.

PMID- 28429486
TI  - Chronic periodontitis and implant dentistry.
AB  - Dental implants are regularly placed in patients with a history of periodontitis,
      even though peri-implant tissues are susceptible to the same host-modulated
      plaque-induced factors that initiate and sustain periodontitis. This article
      endeavors to clarify the evidence regarding the history of periodontitis as a
      risk factor for implant success and survival, and the role of supportive
      periodontal therapy in maintaining implants for individuals with a history of
      periodontitis.

PMID- 28429487
TI  - Effect of orthodontic treatment on the periodontal tissues.
AB  - Reduced periodontal support is a challenge that clinicians often face during
      rehabilitation of compromised dentition. The close and intricate relationship
      between the periodontal tissues and the processes of tooth movement suggest that
      adjunct orthodontic therapy may play an important role in overcoming these
      problems. On the other hand, excessive movement of teeth beyond the anatomic
      boundaries of the alveolar process is commonly believed to contribute to further
      destruction of the periodontal tissues. This review evaluates the clinical
      effects of various orthodontic tooth movements on the surrounding periodontal
      soft tissues and alveolar bone. Another objective was to identify possible
      patient and treatment-related factors that may influence the response of
      periodontal tissue to specific orthodontic treatments. Particular emphasis is
      placed on specific tooth movements, such as extrusion, intrusion, space closure
      and arch expansion. Limitations of current research are also highlighted and
      discussed.

PMID- 28429488
TI  - Interdisciplinary periodontics: the multidisciplinary approach to the planning
      and treatment of complex cases.
AB  - Periodontics cannot be practiced in isolation as frequently many patients have
      multiple dental needs or medical health issues requiring management. In addition,
      pathology may manifest in the periodontal tissues, and the onset and progression
      of periodontitis can be affected by systemic conditions, such as diabetes, and
      vice versa. The focus of this volume of Periodontology 2000 is interdisciplinary
      periodontics, and the articles included discuss the interactions and the
      interrelationshipbetween periodontal tissues/periodontal diseases and
      endodontics, fixed prosthodontics, implant dentistry, esthetics, gerodontology,
      radiology, orthodontics, pediatric dentistry, oral and maxillofacial surgery,
      oral pathology, special needs dentistry and general medicine. Previous volumes of
      Periodontology 2000 have covered some of the interactions between periodontal
      diseases and other dental disciplines, especially implant dentistry, 'and the
      interaction between periodontal disease and systemic disease', but there has not
      been a volume on interdisciplinary periodontics. The intention therefore is to
      show how and why periodontics should be interdisciplinary, as well as the
      benefits of an interdisciplinary approach; in addition, the potential
      consequences of using a discipline in isolation are discussed.

PMID- 28429489
TI  - Transcriptional analysis of the adaptation of Ustilago maydis during growth under
      nitrogen fixation conditions.
AB  - Regulation of genes involved in nitrogen metabolism likely plays a role in the
      ability of fungi to exploit and survive under different environmental situations.
      To learn about the mechanism of adaptation of the biotrophic fungus Ustilago
      maydis from a medium containing a source of fixed nitrogen, to a medium depending
      on the ability to fix N2 by its bacterial endosymbiont, we explored gene
      expression profiles using RNA-Seq analyses under these two conditions. The
      differentially expressed (DE) fungal genes were analyzed, identifying 90 genes
      that were regulated 24 h after shifting the fungus to media lacking ammonium
      nitrate as a nitrogen source. From these, mRNA levels were increased for 49
      genes, whereas 41 were down-regulated. The functional description associated to
      the regulated genes revealed that nine key pathways were represented, including,
      secondary metabolism, the metabolism of nitrogen, amino acid, fatty acid, amino
      sugar and nucleotide sugar, purine, peroxisome, and the regulation of actin
      cytoskeleton. These results suggest that the interplay of U. maydis with its N2
      fixing bacterial endosymbiont is a flexible process that may be active during the
      adaptation of the fungus to the different nitrogen sources.

PMID- 28429490
TI  - Contrast-Enhanced Ultrasound Classification of Previously Indeterminate Renal
      Lesions.
AB  - OBJECTIVES: To determine the utility of contrast-enhanced ultrasound (US) for
      characterizing renal lesions that were indeterminate on prior imaging. METHODS:
      This Institutional Review Board-approved retrospective diagnostic accuracy study
      evaluated all patients who underwent renal contrast-enhanced US examinations from
      2006 to 2015 at our tertiary care hospital. We compared the number of lesions
      definitively characterized by contrast-enhanced US with the indeterminate lesions
      by prior imaging. The accuracy of contrast-enhanced US was compared with the
      final diagnosis by histologic examination and follow-up (mean, 3.63 years).
      Accuracy and agreement estimates were compared with the exact binomial
      distribution to assess statistical significance. RESULTS: A total of 134 lesions
      were evaluated with contrast-enhanced US, and 106 were indeterminate by preceding
      computed tomography, magnetic resonance imaging, or US. Only the largest lesion
      per patient was included in analysis. A total of 95.7% (90 of 94) of the
      previously indeterminate lesions were successfully classified with contrast
      enhanced US. The sensitivity was 100% (20 of 20; 95% confidence interval [CI],
      83%-100%; P < .0001); specificity was 85.7% (18 of 21; 95% CI, 62%-97%; P =
      .0026); positive predictive value was 87.0% (20 of 23; 95% CI, 66%-97%; P =
      .0005); negative predictive value was 100% (18 of 18; 95% CI, 81%-100%; P <
      .001); and accuracy was 90.2% (37 of 41; 95% CI, 80%-98%; P < .0001).
      CONCLUSIONS: Contrast-enhanced US has a high likelihood of definitively
      classifying a renal lesion that is indeterminate by computed tomography, magnetic
      resonance imaging, or conventional US.

PMID- 28429491
TI  - Bringing the human pancreas into focus: new paradigms for the understanding of
      Type 1 diabetes.
AB  - Type 1 diabetes affects increasingly large numbers of people globally (including
      at least half a million children under the age of 14 years) and it remains an
      illness with life-long and often devastating consequences. It is surprising,
      therefore, that the underlying aetiology of Type 1 diabetes remains poorly
      understood. This is largely because the cellular and molecular processes leading
      to the loss of beta cells in the pancreas have rarely been studied at, or soon
      after, the onset of disease. Where such studies have been undertaken, a number of
      surprises have emerged which serve to challenge conventional wisdom. In
      particular, it is increasingly understood that the process of islet inflammation
      (insulitis) is much less florid in humans than in certain animal models.
      Moreover, the profile of immune cells involved in the inflammatory attack on beta
      cells is variable and this variation occurs at the level of individual patients.
      As a result, two distinct profiles of insulitis have now been defined that are
      differentially aggressive and that might, therefore, require specifically
      tailored therapeutic approaches to slow the progression of disease. In addition,
      the outcomes are also different in that the more aggressive form (termed
      'CD20Hi') is associated with extensive beta-cell loss and an early age of disease
      onset (<7 years), while the less aggressive profile (known as 'CD20Lo') is
      associated with later onset (>13 years) and the retention of a higher proportion
      of residual beta cells. In the present review, these new findings are explained
      and their implications evaluated in terms of future therapies.

PMID- 28429492
TI  - Body weight, gender and pregnancy affect enantiomer-specific ketorolac
      pharmacokinetics.
AB  - AIMS: Although ketorolac analgesia is linked only to the S-enantiomer, there is
      limited information on the stereo-selective pharmacokinetics of this agent. We
      studied the stereo-selective pharmacokinetics of ketorolac in a pooled dataset of
      two studies, with women at delivery and 4-5 months postpartum, and males and
      nonpregnant females. METHODS: Nonlinear mixed-effect modelling was used to
      evaluate the stereo-selective pharmacokinetics of ketorolac tromethamine after a
      single intravenous injection immediately after delivery (n = 41), 4-5 months
      postpartum (n = 8, paired), and in male (n = 12) and nonpregnant female (n = 14)
      subjects. All of the males and six of the nonpregnant females were recruited from
      another study, in which they were undergoing blood sampling for 24 h. All
      remaining cases underwent blood sampling for 8 h. RESULTS: For both the R- and S
      enantiomers, body weight affected ketorolac clearance. In addition, clearance for
      both enantiomers was 36% [95% confidence interval (CI) 15%, 58%] higher in male
      than in female subjects of the same body weight, and 55% (95% CI 33%, 78%) higher
      in women at delivery than in nonpregnant women of the same body weight. Women at
      delivery also had a 27% (95% CI 8%, 46%) higher distribution volume than
      nonpregnant women. The proportional effects of the covariates were not
      significantly different for the two ketorolac enantiomers. CONCLUSIONS: Besides
      the anticipated impact of body weight on clearance, R- and S-ketorolac clearance
      is increased in male subjects and in women at delivery. To reach an exposure
      equivalent to that in nonpregnant women, males should receive a 36% increased
      ketorolac dose and pregnant women a 55% increased dose, in addition to a dose
      adjustment by body weight.

PMID- 28429493
TI  - Cutting off half of QRS duration can cause overcorrection of QT interval in left
      bundle branch block.

PMID- 28429494
TI  - A Modular Approach to Inorganic Phosphazane Macrocycles.
AB  - Inorganic macrocycles, based on non-carbon backbones, present exciting synthetic
      challenges in the systematic assembly of inorganic molecules, as well as new
      avenues in host-guest and supramolecular chemistry. Here we demonstrate a new
      high-yielding modular approach to a broad range of trimeric and hexameric S- and
      Se-bridged inorganic macrocycles based on cyclophosphazane frameworks, using the
      building blocks [S=(H)P(MU-NR)]2 . The method involves the in situ generation of
      the key intermediate [E....._ (S....._ )P(MU-NR)]22- (E=S, Se) dianion, which can
      be reacted with electrophilic [ClP(MU-NR)]2 to give PIII /PV hexameric rings or
      reacted with I2 to give trimeric PV variants. Important issues which are
      highlighted in this work are the competitive bridging ability of S versus Se in
      these systems and the synthesis of the first air-stable and chiral inorganic
      macrocycles.

PMID- 28429495
TI  - Moisture-Responsive Wrinkling Surfaces with Tunable Dynamics.
AB  - The wrinkle dynamics (such as reversibility and stability) of human skin are
      affected by the external stimuli, as well as the skin's structure and mechanical
      properties. Inspired by these tunable responses, three types of moisture
      responsive wrinkle dynamics are achieved, for the first time, through a single
      film-substrate system. These dynamics include: (1) completely reversible wrinkles
      formation; (2) irreversible wrinkles formation I: the initially formed wrinkles
      can be permanently erased and never reappear; and (3) irreversible wrinkles
      formation II: once the wrinkles form, they can no longer be erased. The key to
      success is to control the stiffness and thickness ratios of the film and the
      substrate, and tailor the crosslink degree/gradient of the film to allow for
      moisture-dependent changes of modulus and swelling degree. These unique
      responsive dynamics motivate the invention of a series of optical devices
      triggered by moisture, including anticounterfeit tabs, encryption devices, water
      indicators, light diffusors, and antiglare films. This study also paves the road
      for further understanding of the skin wrinkling dynamics and manipulation.

PMID- 28429496
TI  - SponTaneous Respiration using IntraVEnous anaesthesia (STRIVE) facilitates
      fibreoptic intubation through supraglottic airway device.

PMID- 28429497
TI  - In response to stomal maturation does not increase the rate of tracheocutaneous
      fistulas.

PMID- 28429498
TI  - Separate neural systems for behavioral change and for emotional responses to
      failure during behavioral inhibition.
AB  - To analyze the involvement of different brain regions in behavioral inhibition
      and impulsiveness, differences in activation were investigated in fMRI data from
      a response inhibition task, the stop-signal task, in 1709 participants. First,
      areas activated more in stop-success (SS) than stop-failure (SF) included the
      lateral orbitofrontal cortex (OFC) extending into the inferior frontal gyrus
      (ventrolateral prefrontal cortex, BA 47/12), and the dorsolateral prefrontal
      cortex (DLPFC). Second, the anterior cingulate and anterior insula (AI) were
      activated more on failure trials, specifically in SF versus SS. The interaction
      between brain region and SS versus SF activations was significant (P = 5.6 * 10-8
      ). The results provide new evidence from this "big data" investigation consistent
      with the hypotheses that the lateral OFC is involved in the stop-related
      processing that inhibits the action; that the DLPFC is involved in attentional
      processes that influence task performance; and that the AI and anterior cingulate
      are involved in emotional processes when failure occurs. The investigation thus
      emphasizes the role of the human lateral OFC BA 47/12 in changing behavior, and
      inhibiting behavior when necessary. A very similar area in BA47/12 is involved in
      changing behavior when an expected reward is not obtained, and has been shown to
      have high functional connectivity in depression. Hum Brain Mapp, 2017. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28429499
TI  - Atrial fibrillation patients with isolated pulmonary veins: Is sinus rhythm
      achievable?
AB  - BACKGROUND: The cornerstone of atrial fibrillation (AF) ablation is isolation of
      the pulmonary veins (PVs). Patients with recurrent AF undergoing repeat ablation
      usually have PV reconnection (PVr). The ablation strategy and outcome of patients
      undergoing repeat ablation who have persistent isolation of all PVs (PVi) at the
      time of repeat ablation is unknown. METHODS AND RESULTS: We studied consecutive
      patients with recurrent AF undergoing repeat ablation and compared patients with
      PVi to those with PVr. One hundred fifty-two patients underwent repeat ablation,
      and of these, 25 patients (16.4%) had PVi. Patients with PVi underwent ablation
      targeting any isoproterenol induced AF triggers, atrial substrate, or inducible
      atrial tachycardias or flutters. Patients with PVi compared to PVr were more
      likely to have a history of persistent AF (64% vs. 26%; P < 0.0001), obesity (BMI
      30.4 vs. 28.2; P = 0.05), and prior use of contact force sensing catheters (28%
      vs. 0.8%, P < 0.0001). After a mean follow-up of 19 +/- 15 months, 56% of PVi
      patients remained in sinus rhythm compared to 76.3% of PVr patients (P = 0.036).
      In a multivariable model, PVi patients and those with cardiomyopathy had a higher
      risk of recurrent atrial tachyarrhythmias (HR = 3.6 95%, CI 1.6-8.3, P = 0.002
      and HR = 6.2, 95% CI 2.3-16.3, P < 0.0001, respectively). CONCLUSION: In patients
      who have all PVs isolated at the time of the redo AF ablation, a strategy of
      targeting non-PV AF triggers and inducible flutters can still lead to AF freedom
      in more than half of patients. Patients with PVr, however, have a better long
      term outcome.

PMID- 28429500
TI  - Electrocardiographic appearance of aortic stenosis before and after aortic valve
      replacement.
AB  - BACKGROUND: So far, the specific appearance of QRS complex, ST-segment, and T
      wave was observed in aortic stenosis (AS). S-wave dynamic change in leads V1 -V3
      was not reported in AS. METHODS: In a single-center, prospective study, we
      included a total number of 1.175 patients who underwent surgical aortic valve
      replacement (AVR). We conducted 3-year gathering of patients with symptomatic and
      asymptomatic severe AS, and separated them by hemodynamic stability into groups A
      and B, through EFLV (of more or less than 50%), AVA (of more or less than 0.9 cm2
      ), PG (between 55 and 75 mm Hg or over 75 mm Hg), and end-diastolic LV dimension
      (of more or less than 56 mm). We evaluated the impact of S-wave magnitude in
      right precordial leads before and after AVR in all patients. We followed S-wave
      changes in electrocardiogram altogether with hemodynamic measurements derived
      from echocardiography. RESULTS: Analysis of echocardiographic parameters,
      measured in patients before surgery, did not show statistical significance
      between asymptomatic and symptomatic group. The statistical significance was
      observed in the change in S-wave magnitude in the right precordial leads in both
      subsets of patients before AVR. We found statistically significant predictive
      value of S-wave magnitude in leads V2 -V3 for dependent variables PG and end
      diastolic LV dimension. CONCLUSIONS: S-wave changes in right precordial leads can
      predict increase in PG and critical narrowing of AVA, suggestive of timely
      referral for AVR.

PMID- 28429501
TI  - Formation of macromolecules in wheat gluten/starch mixtures during twin-screw
      extrusion: effect of different additives.
AB  - BACKGROUND: Wheat gluten comprises a good quality and inexpensive vegetable
      protein with an ideal amino acid composition. To expand the potential application
      of wheat gluten in the food industry, the effect of different additives on the
      physicochemical and structural properties of wheat gluten/starch mixtures during
      twin-screw extrusion was investigated. RESULTS: Macromolecules were observed to
      form in wheat gluten/starch mixtures during twin-screw extrusion, which may be
      attributed to the formation of new disulfide bonds and non-covalent interactions,
      as well as Maillard reaction products. Additionally, the water retention capacity
      and in vitro protein digestibility of all extruded wheat gluten/starch products
      significantly increased, whereas the nitrogen solubility index and free
      sulfhydryl group (SH) content decreased, during twin-screw extrusion. Secondary
      structural analysis showed that alpha-helices disappeared with the concomitant
      increase of antiparallel beta-sheets, demonstrating the occurrence of protein
      aggregation. Microstructures suggested that the irregular wheat gluten granular
      structure was disrupted, with additive addition favoring transformation into a
      more layered or fibrous structure during twin-screw extrusion. CONCLUSION: The
      findings of the present study demonstrate that extrusion might affect the texture
      and quality of extruded wheat gluten-based foods and suggest that this process
      might serve as a basis for the high-value application of wheat gluten products.
      (c) 2017 Society of Chemical Industry.

PMID- 28429502
TI  - Involvement of ERK1/2 in Cx43 depression induced by macrophage migration
      inhibitory factor in atrial myocytes.
AB  - Connexin 43 (Cx43) plays an important role in the pathogenesis of atrial
      fibrillation (AF). The present study sought to investigate the effect of
      macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, on Cx43
      expression and activity and determine the intracellular signalling pathways. Cx43
      protein and mRNA levels were assayed using immunofluorescence, real-time
      polymerase chain reaction (PCR), and western blot. We found that increased MIF
      and extracellular regulated protein kinases (ERK) expression was accompanied by a
      significant reduction in Cx43 protein expression in atrial tissues from patients
      with AF compared with those with sinus rhythm. In cultured atrium-derived
      myocytes (HL-1 cells), mouse recombinant-MIF (rMIF, 20 or 40 nmol/L, 24 hours)
      down-regulated gene and protein expression of Cx43 in a concentration-dependent
      manner. U0126, a specific inhibitor of mitogen-activated protein kinase kinase
      (MAPKK) could reverse the decrease in expression of Cx43 protein induced by rMIF.
      Further studies revealed that rMIF (40 nmol/L, 15, 30, and 45 minutes) was able
      to stimulate phospho-Erk1/2 (Thr202/Tyr204) production in a time-dependent
      manner. These results suggest that MIF is involved in the pathogenesis of AF,
      probably by down-regulating the protein and gene expression of Cx43 via ERK1/2
      kinase activation. Our findings represent a potential pathogenic mechanism in AF.

PMID- 28429503
TI  - Cleavage of a P=P Double Bond Mediated by N-Heterocyclic Carbenes.
AB  - The reaction of the bulky diphosphenes (Rind)P=P(Rind) (1; Rind=1,1,3,3,5,5,7,7
      octa-R-substituted s-hydrindacen-4-yl) with two molecules of N-heterocyclic
      carbene (NHC; 1,3,4,5-tetramethylimidazol-2-ylidene) resulted in the quantitative
      formation of the NHC-bound phosphinidenes NHC->P(Rind) (2), along with the
      cleavage of the P=P double bond. The reaction times are dependent on the steric
      size of the Rind groups (11 days for 2 a (R=Et) and 2 h for 2 b (R=Et, Me) at
      room temperature). The mechanism for the double bond-breaking is proposed to
      proceed via the formation of the NHC-coordinated, highly polarized diphospehenes
      3 as an intermediate. Approach of a second NHC to 3 induces P-P bond cleavage and
      P-C bond formation, which proceeds through a transition state with a large
      negative Gibbs energy change to afford the two molecules of 2, thus being the
      rate-determining step of the overall reaction with the activation barriers of
      80.4 for 2 a and 29.1 kJ mol-1 for 2 b.

PMID- 28429504
TI  - Induced pluripotent stem cells reduce neutrophil chemotaxis via activating GRK2
      in endotoxin-induced acute lung injury.
AB  - BACKGROUND AND OBJECTIVE: We investigated the effect of induced pluripotent stem
      cells (iPSCs) in moderating neutrophil chemotaxis in endotoxin-induced acute lung
      injury (ALI). METHODS: Male C57BL/6 mice at 8-12 weeks of age were studied.
      Murine iPSCs were delivered through the tail veins of mice 4 h after
      intratracheal instillation of endotoxin. Lung histopathological findings,
      neutrophil counts in peripheral blood and bronchoalveolar lavage fluid (BALF),
      bone marrow (BM) cell distribution, expression of chemokine receptors and
      regulatory signalling pathways were analysed after 24 h. Human neutrophils
      isolated from acute respiratory distress syndrome patients were used in a cell
      migration assay. RESULTS: iPSCs significantly decreased the histopathological
      changes of ALI in mice compared to treatment with control cells. Numbers and
      activity levels of neutrophils in BALF were reduced in iPSC-treated ALI mice. The
      iPSC therapy restored neutrophil counts in the peripheral blood of ALI mice, but
      the percentages of mature neutrophils in BM were similar between iPSC-treated and
      -untreated groups. The iPSCs mediated a downregulation of the chemotactic
      response to endotoxin by reducing chemokine (C-X-C motif) receptor 2 (CXCR2)
      expression on mouse peripheral blood neutrophils. This result was confirmed by an
      in vitro human neutrophil migration assay. In addition, iPSCs or conditioned
      medium from iPSCs enhanced expression of G protein-coupled receptor kinase 2
      (GRK2) on the surface of blood neutrophils in ALI mice. CONCLUSION: iPSCs reduce
      neutrophil chemotaxis in endotoxin-induced ALI. These effects are associated with
      an enhancement of GRK2 activity and reduction of CXCR2 expression.

PMID- 28429505
TI  - Total Synthesis of (-)-Albocycline.
AB  - The macrolactone natural product (-)-albocycline is a promising antibiotic
      candidate for the treatment of both methicillin resistant Staphylococcus aureus
      (MRSA) and vancomycin-resistant strains. Herein we report a concise total
      synthesis of (-)-albocycline in 14 steps from commercially available methyl (R)-3
      hydroxybutyrate. Novel key steps include the highly regio- and stereoselective
      reactions of chiral N-sulfinyl metallodienamines (NSMDs) with aldehydes and the
      Davis oxaziridine, in addition to the Horner-Wadsworth-Emmons olefination of N
      sulfinyl imines.

PMID- 28429506
TI  - A Robust and Conductive Black Tin Oxide Nanostructure Makes Efficient Lithium-Ion
      Batteries Possible.
AB  - SnO2 -based lithium-ion batteries have low cost and high energy density, but
      their capacity fades rapidly during lithiation/delithiation due to phase
      aggregation and cracking. These problems can be mitigated by using highly
      conducting black SnO2-x , which homogenizes the redox reactions and stabilizes
      fine, fracture-resistant Sn precipitates in the Li2 O matrix. Such fine Sn
      precipitates and their ample contact with Li2 O proliferate the reversible Sn ->
      Li x Sn -> Sn -> SnO2 /SnO2-x cycle during charging/discharging. SnO2-x electrode
      has a reversible capacity of 1340 mAh g-1 and retains 590 mAh g-1 after 100
      cycles. The addition of highly conductive, well-dispersed reduced graphene oxide
      further stabilizes and improves its performance, allowing 950 mAh g-1 remaining
      after 100 cycles at 0.2 A g-1 with 700 mAh g-1 at 2.0 A g-1 . Conductivity
      directed microstructure development may offer a new approach to form advanced
      electrodes.

PMID- 28429507
TI  - Mucinous hidradenoma in a child-A case report and review of the literature.
AB  - Hidradenomas are benign tumors of the sweat glands that are rarely reported in
      childhood. The presence of mucinous change in hidradenomas, which consists of
      variable numbers of mucin-rich goblet cells, is occasionally observed in some
      adult clinical practices. However, it has not been previously reported in the
      pediatric population. Herein, we present a unique case of a mucinous hidradenoma
      presenting on the thigh of a 3-year-old boy. The clinical presentation and
      histological features of the case, along with a literature review of published
      case reports of pediatric hidradenomas are described. We present this case in
      order to highlight this variant of hidradenoma and to reinforce its inclusion in
      the differential diagnosis of neoplasms/conditions of childhood with mucinous
      differentiation.

PMID- 28429508
TI  - Immunophenotyping and activation status of maternal peripheral blood leukocytes
      during pregnancy and labour, both term and preterm.
AB  - The onset of labour in rodents and in humans is associated with physiological
      inflammation which is manifested by infiltration of activated maternal peripheral
      leukocytes (mPLs) into uterine tissues. Here, we used flow cytometry to
      immunophenotype mPLs throughout gestation and labour, both term and preterm.
      Peripheral blood was collected from non-pregnant women and pregnant women in the
      1st, 2nd and 3rd trimesters. Samples were also collected from women in active
      labour at term (TL) or preterm (PTL) and compared with women term not-in-labour
      (TNIL) and preterm not-in-labour (PTNIL). Different leukocyte populations were
      identified by surface markers such as CD45, CD14, CD15, CD3, CD4, CD8, CD19 and
      CD56. Their activation status was measured by the expression levels of CD11b,
      CD44, CD55, CD181 and CD192 proteins. Of all circulating CD45+ leukocytes, we
      detected significant increases in CD15+ granulocytes (i) in pregnant women versus
      non-pregnant; (ii) in TL women versus TNIL and versus pregnant women in the
      1st/2nd/3rd trimester; (iii) in PTL women versus PTNIL. TL was characterized by
      (iv) increased expressions of CD11b, CD55 and CD192 on granulocytes; (v)
      increased mean fluorescent intensity (MFI) of CD55 and CD192 on monocytes; (vi)
      increased CD44 MFI on CD3+ lymphocytes as compared to late gestation. In summary,
      we have identified sub-populations of mPLs that are specifically activated in
      association with gestation (granulocytes) or with the onset of labour
      (granulocytes, monocytes and lymphocytes). Additionally, beta regression analysis
      created a set of reference values to rank this association between immune markers
      of pregnancy and to identify activation status with potential prognostic and
      diagnostic capability.

PMID- 28429509
TI  - CO2 permeability and carbonic anhydrase activity of rat cardiomyocytes.
AB  - AIM: To determine the CO2 permeability (PCO2 ) of plasma membranes of
      cardiomyocytes. These cells were chosen because heart possesses the highest rate
      of O2 consumption/CO2 production in the body. METHODS: Cardiomyocytes were
      isolated from rat hearts using the Langendorff technique. Cardiomyocyte
      suspensions exhibited a vitality of 2-14% and were studied by the previously
      described mass spectrometric 18 O-exchange technique deriving PCO2 . We showed by
      mass spectrometry and by carbonic anhydrase (CA) staining that non-vital
      cardiomyocytes are free of CA and thus do not contribute to the mass
      spectrometric signal, which is determined exclusively by the fully functional
      vital cardiomyocytes. RESULTS: Lysed cardiomyocytes yielded an intracellular CA
      activity for vital cells of 5070; that is, the rate of CO2 hydration inside the
      cell is accelerated 5071-fold. Using this number, analyses of the mass
      spectrometric recordings from cardiomyocyte suspensions yield a PCO2 of 0.10 cm s
      1 (SD +/- 0.06, n = 15) at 37  degrees C. CONCLUSION: In comparison with the PCO2
      of other cells, this value is quite high and about identical to that of the human
      red cell membrane. As no major protein CO2 channels such as aquaporins 1 and 4
      are present in rat cardiac sarcolemma, the high PCO2 of this membrane is likely
      due to its low cholesterol content of about 0.2 (mol cholesterol).(mol total
      membrane lipids)-1 . Previous work predicted a PCO2 of >=0.1 cm s-1 from this
      level of cholesterol. We conclude that the low cholesterol establishes a PCO2
      high enough to render the membrane resistance to CO2 diffusion almost negligible,
      even under conditions of maximal O2 consumption of the heart.

PMID- 28429510
TI  - Mixing of water masses caused by a drifting iceberg affects bacterial activity,
      community composition and substrate utilization capability in the Southern Ocean.
AB  - The number of icebergs produced from ice-shelf disintegration has increased over
      the past decade in Antarctica. These drifting icebergs mix the water column,
      influence stratification and nutrient condition, and can affect local
      productivity and food web composition. Data on whether icebergs affect
      bacterioplankton function and composition are scarce, however. We assessed the
      influence of iceberg drift on bacterial community composition and on their
      ability to exploit carbon substrates during summer in the coastal Southern Ocean.
      An elevated bacterial production and a different community composition were
      observed in iceberg-influenced waters relative to the undisturbed water column
      nearby. These major differences were confirmed in short-term incubations with
      bromodeoxyuridine followed by CARD-FISH. Furthermore, one-week bottle incubations
      amended with inorganic nutrients and carbon substrates (a mix of substrates,
      glutamine, N-acetylglucosamine, or pyruvate) revealed contrasting capacity of
      bacterioplankton to utilize specific carbon substrates in the iceberg-influenced
      waters compared with the undisturbed site. Our study demonstrates that the
      hydrographical perturbations introduced by a drifting iceberg can affect
      activity, composition, and substrate utilization capability of marine
      bacterioplankton. Consequently, in a context of global warming, increased
      frequency of drifting icebergs in polar regions holds the potential to affect
      carbon and nutrient biogeochemistry at local and possibly regional scales.

PMID- 28429511
TI  - In Situ Construction of Stable Tissue-Directed/Reinforced Bifunctional
      Separator/Protection Film on Lithium Anode for Lithium-Oxygen Batteries.
AB  - To achieve a high reversibility and long cycle life for Li-O2 battery system, the
      stable tissue-directed/reinforced bifunctional separator/protection film (TBF) is
      in situ fabricated on the surface of metallic lithium anode. It is shown that a
      Li-O2 cell composed of the TBF-modified lithium anodes exhibits an excellent
      anodic reversibility (300 cycles) and effectively improved cathodic long lifetime
      (106 cycles). The improvement is attributed to the ability of the TBF, which has
      chemical, electrochemical, and mechanical stability, to effectively prevent
      direct contact between the surface of the lithium anode and the highly reactive
      reduced oxygen species (Li2 O2 or its intermediate LiO2 ) in cell. It is believed
      that the protection strategy describes here can be easily extended to other next
      generation high energy density batteries using metal as anode including Li-S and
      Na-O2 batteries.

PMID- 28429512
TI  - Tailored approach for management of ventricular tachycardia in cardiac
      sarcoidosis.
AB  - INTRODUCTION: Treating ventricular tachycardia (VT) in patients with cardiac
      sarcoidosis (CS) is challenging as patients present in different phase of the
      disease (inflammatory, scar, or sometimes both). A  customized approach to
      treatment is required for better outcomes. We describe our experience in the
      management of VT in CS based on the phase of the disease. METHODS AND RESULTS:
      Patients were considered to have myocardial inflammation if there was an
      increased myocardial 18 fluorodeoxy glucose (FDG) uptake in PET-CT scan of the
      chest (n = 14). These patients were treated with antiarrhythmic drugs (AADs) and
      immunosuppression. Patients with scar related VT (without active inflammation)
      were managed with AADs and underwent radiofrequency ablation (RFA) if
      unresponsive to drug therapy (n = 4). Patients previously treated for CS who
      presented with VT and evidence of reactivation (abnormal FDG uptake) after a
      quiescent period of 6 months were treated with intensified immunosuppression
      alongside AADs (n = 3/14). Patients with myocardial inflammation responded well
      to immunosuppression. Patients with drug resistant VT in the scar phase responded
      well to RFA. Four patients in the inflammatory group had recurrence of VT during
      follow-up of whom 3 were found to have disease reactivation. Intensified
      immunosuppression suppressed VT in all 3 patients. In 1 patient, VT recurrence
      was found to be scar related and required RFA for control. CONCLUSION: Tailoring
      therapy for VT in CS according to the phase of disease results in good clinical
      outcome and avoids unnecessary immunosuppression.

PMID- 28429514
TI  - Maternal metabolic adaptations to pregnancy among young women in Cebu,
      Philippines.
AB  - OBJECTIVES: Evidence that fetal development has long-term impacts on health has
      increased interest in maternal-fetal nutrient exchange. Although maternal
      metabolism is known to change during gestation to accommodate fetal nutrient
      demands, little is known about these modifications outside of a Western, clinical
      context. This study characterizes maternal metabolic adaptations to pregnancy,
      and their associations with offspring birth weight (BW), among women living in
      the Philippines. METHODS: Fasting glucose, triglycerides, insulin, leptin, and
      adiponectin were assessed in 808 participants in the Cebu Longitudinal Health and
      Nutrition Survey (Metropolitan Cebu, Philippines). Cross-sectional relationships
      between metabolites and hormones and gestational and lactational status were
      evaluated. Among the subset of currently pregnant women, associations between
      maternal glucose and triglycerides and offspring BW were also examined. RESULTS:
      Women in their second and third trimesters had significantly lower fasting
      glucose and adiponectin compared to nulliparous women, and leptin levels and
      triglyceride levels were notably higher late in pregnancy (all P < .05). Among
      pregnant women, fasting glucose was a positive predictor of offspring BW, but
      only in males (P = .012, R2  = .28). Hormones and metabolites in post-partum
      women trend back toward levels found in nulliparous women, with some differences
      by breastfeeding status. CONCLUSIONS: We find evidence for marked changes in
      maternal lipid and carbohydrate metabolism during pregnancy, consistent with
      known adaptations to support fetal growth. The finding of sex-specific
      relationships between maternal glucose and offspring BW adds to evidence for
      greater impacts of the maternal-gestational environment on biology and health in
      male offspring.

PMID- 28429513
TI  - Distribution and hormonal characterization of primary murine L cells throughout
      the gastrointestinal tract.
AB  - AIMS/INTRODUCTION: Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine
      L cells is an incretin that potentiates insulin secretion and is already applied
      in therapies for type 2 diabetes. However, detailed examination of L cells
      throughout the gastrointestinal tract remains unclear, because of difficulties in
      purifying scattered L cells from other cells. In the present study, we identified
      characteristics of L cells of the upper small intestine (UI), the lower small
      intestine (LI) and the colon using glucagon-green fluorescent protein-expressing
      mice that express GFP driven by the proglucagon promoter. MATERIALS AND METHODS:
      The localization and density of primary L cells were evaluated by anti-green
      fluorescent protein antibody reactivity. GLP-1 content, messenger ribonucleic
      acid (mRNA) expression levels and secretion in purified L cells were measured.
      RESULTS: The number of L cells significantly increased toward the colon. In
      contrast, the GLP-1 content and secretion from L cells were higher in the UI than
      in the LI and colon. L cells from the UI and LI expressed notably high mRNA
      levels of the transcription factor, islet 1. The mRNA expression levels of
      peptide YY in L cells were higher in the LI than in the UI and colon. The mRNA
      expression levels of gastric inhibitory polypeptide in L cells from the UI were
      significantly higher compared with those from the LI and colon. CONCLUSIONS: L
      cells show different numbers and characteristics throughout the gut, and they
      express different mRNA levels of transcription factors and gastrointestinal
      hormones. These results contribute to the therapeutic application of promoting
      GLP-1 release from L cells for the treatment of type 2 diabetes.

PMID- 28429515
TI  - A device to measure secretion of individual sweat glands for diagnosis of
      peripheral neuropathy.
AB  - There is a need for quantitative, precise assessment of small fiber peripheral
      nerve function. We tested a customized camera device and protocol designed to
      quantify secretions of individual sweat glands (SGs). Testing was performed on
      178 healthy controls and 20 neuropathy subjects. Sweating was stimulated on a
      2.25 cm2 skin area by iontophoresis of pilocarpine. The camera imaged sweat from
      50 to 400 sweat ducts. We calculated secretion rate of individual SGs, total
      sweat volume, and number of secreting SGs at four body sites. Neuropathy subjects
      were tested at the two distal sites to demonstrate the device's capability to
      detect abnormal sudomotor function. Normal ranges were calculated for each body
      site. Neuropathy subjects had lower sweat rates per SG, lower total sweat, and
      lower SG density. The normal values decreased with advancing age, were lower in
      females, and differed between body sites. There was good agreement with repeat
      testing. The device provides reliable, precise quantitative measures of sweat
      secretion from single SGs for characterization of sudomotor nerve function in
      healthy control subjects and in subjects with known peripheral neuropathy. The
      test combines the capabilities of existing tests of sudomotor function while
      providing additional capabilities.

PMID- 28429516
TI  - N-Heterocyclic Carbene Catalyzed [4+2] Annulation of Enals via a Double
      Vinylogous Michael Addition: Asymmetric Synthesis of 3,5-Diaryl Cyclohexenones.
AB  - A strategy for the N-heterocyclic carbene (NHC) catalyzed asymmetric synthesis of
      3,5-diaryl substituted cyclohexenones has been developed via oxidative [4+2]
      annulation of enals and alkenylisoxazoles. It is the first example of using NHC
      organocatalysis in a double vinylogous Michael type reaction, a challenging but
      highly desirable topic. This unprecedented protocol affords good yields as well
      as high to excellent diastereo- and enantioselectivities.

PMID- 28429517
TI  - Primary laryngeal sarcomas in a Mexican population: Case series of eleven cases.

PMID- 28429518
TI  - Full blown nephrotic syndrome due to unilateral obstruction of the uretero-pelvic
      junction.

PMID- 28429519
TI  - The incidence and costs of bacteremia due to lack of gentamicin lock solutions
      for dialysis catheters.
AB  - The use of antibiotic lock solutions as prophylaxis for catheter-associated blood
      stream infection (CRBSI) has been shown to be effective in previous randomized
      controlled trials. However, the cost-effectiveness of this approach had not been
      studied. In 2012, the routine gentamicin-heparin lock solution used in Auckland
      City Hospital was withdrawn from the market, leading to a change to heparin-only
      lock. This was then replaced with gentamicin-citrate lock in 2014. This situation
      allowed review of the CRBSI rate and financial impact of different catheter lock
      solutions. A retrospective audit was performed from 1 January 2011 to 31 December
      2015 to investigate the rate of culture-proven CRBSI in patients with tunneled
      cuffed dialysis catheters. There were 89 cases of CRBSI involving 64 patients in
      the 5-year period. In comparison with the heparin-only lock, both gentamicin
      heparin and gentamicin-citrate locks had a significantly lower rate of
      bacteremia, with rate ratios of 0.46 (confidence interval 0.30-0.72) and 0.11
      (confidence interval 0.05-0.22), respectively. The inpatient costs as a
      consequence of the CRBSI were NZ$27 792 per 1000 catheter days for heparin-only
      lock, NZ$10 608.56 per 1000 catheter days for gentamicin-heparin lock, and NZ$
      1898.45 per 1000 catheter days for gentamicin-citrate lock. The lack of
      antibiotic lock solutions led to an increase in bacteremia rates and higher
      financial cost for inpatient management of bacteremia. Our findings highlight the
      importance of consistent supply of pharmaceuticals.

PMID- 28429520
TI  - Performance in adolescents of the two Japanese serum creatinine based estimated
      glomerular filtration rate equations, for adults and paediatric patients: A study
      of the Japan Renal Biopsy Registry and Japan Kidney Disease Registry from 2007 to
      2013.
AB  - There are two different Japanese serum creatinine-based equations for estimated
      glomerular filtration rate (eGFR), for adults and paediatric patients, with both
      equations deemed applicable to 18-year-old subjects. This study assessed the
      relative accuracy of the two equations in assessing eGFR in patients aged 18
      years with chronic kidney disease. A total of 3042 patients (1679 males and 1363
      females), aged 2-20 years, who were registered in the Japan Renal Biopsy Registry
      or the Japan Kidney Disease Registry between 2007 and 2013 were evaluated. eGFR
      values derived from formulas for children (Uemura's formula) and adults (the 3
      variable Japanese formula) were calculated and compared, especially in patients
      aged 18 years. At all ages, but especially at younger ages, eGFR was
      significantly higher when calculated with the adult than the paediatric formula.
      This finding was also observed in 18-year-old adolescents with eGFR <90 mL/min
      per 1.73 m2 (P = 0.026). However, the mean difference between the two calculated
      eGFRs was only 2.79 mL/min per 1.73 m2 . These findings indicate that both
      creatinine-based equations used to calculate eGFR rate in Japanese children and
      adults with chronic kidney disease could be used to determine eGFR in 18-year-old
      subjects, with the difference between the two within permissible levels for
      clinical use.

PMID- 28429521
TI  - Mycobacterium chlorophenolicum: An uncommon cause of peritonitis in a peritoneal
      dialysis patient.

PMID- 28429522
TI  - Globotriaosylsphingosine induces oxidative DNA damage in cultured kidney cells.
AB  - Fabry disease (FD) is a lysosomal disorder caused by mutations leading to a
      deficient activity alpha-galactosidase A with progressive and systemic
      accumulation of its substrates. Substrates deposition is related to tissue damage
      in FD, but the underlying molecular mechanisms remain not completely understood.
      DNA damage has been associated with disease progression in chronic diseases and
      was recently described in high levels in Fabry patients. Once renal complications
      are major morbidity causes in FD, we investigated the effects of the latest
      biomarker for FD - globotriaosylsphingosine (lyso-Gb3) in a cultured renal
      lineage - human embryonic kidney cells (HEK-293 T) - on DNA damage. In
      concentrations found in Fabry patients, lyso-Gb3 induced DNA damage (by alkaline
      comet assay) with oxidative origin in purines and pyrimidines (by comet assay
      with endonucleases). These data provide new information about a deleterious
      effect of lyso-Gb3 and could be useful to studies looking for new therapeutic
      strategies to FD.

PMID- 28429523
TI  - Poly-cytosine DNA as a High-Affinity Ligand for Inorganic Nanomaterials.
AB  - Attaching DNA to nanomaterials is the basis for DNA-directed assembly, sensing,
      and drug delivery using such hybrid materials. Poly-cytosine (poly-C) DNA is a
      high affinity ligand for four types of commonly used nanomaterials, including
      nanocarbons (graphene oxide and single-walled carbon nanotubes), transition metal
      dichalcogenides (MoS2 and WS2 ), metal oxides (Fe3 O4 and ZnO), and metal
      nanoparticles (Au and Ag). Compared to other homo-DNA sequences, poly-C DNA has
      the highest affinity for the first three types of materials. Using a diblock DNA
      containing a poly-C block to attach to surfaces, the target DNA was successfully
      hybridized to the other block on graphene oxide more efficiently than that
      containing a typical poly-A block, especially in the presence of non-specific
      background DNA, proteins, or surfactants. This work provides a simple solution
      for functionalizing nanomaterials with non-modified DNA and offers new insights
      into DNA biointerfaces.

PMID- 28429524
TI  - The investigation of genetic and clinical features in Chinese patients with
      juvenile amyotrophic lateral sclerosis.
AB  - Juvenile amyotrophic lateral sclerosis (JALS) occurs at an age of onset below 25
      years with a heterogeneous disease onset location, variable progression and
      survival time. To investigate whether an ALS gene profile could resolve any
      aspects of clinical symptom heterogeneity, we have used targeted sequencing
      technology in a cohort of 12 JALS patients of Chinese descent. We detected 5
      likely pathogenic mutations, 2 in familial probands and 3 in sporadic patients.
      One was a known TARDBP mutation (p.G348V) and 4 were FUS frameshift mutations
      including a known p.Gln519Ilefs*9 mutation and 3 novel mutations,
      p.Gly515Valfs*14, p.Gly486Profs*30, and p.Arg498Alafs*32. Of the 4 FUS mutations,
      2 were able to be confirmed as de novo mutations. The TARDBP mutation carrier
      showed a classic ALS phenotype. All patients with FUS mutations experienced limb
      weakness at an early age and developed bulbar symptoms during the disease course.
      FUS mutations have previously been associated with increased JALS disease
      progression, however, we found a large range 12 to 84 months in disease survival
      (mean 58.2 months). Our results justify future screening for variants in FUS as
      it remains the most frequent genetic determinant of early onset, JALS (found in
      30% of our patients).

PMID- 28429525
TI  - Induction chemotherapy followed by radiochemotherapy for locally advanced head
      and neck cancer as an individual treatment approach-Feasibility, safety and
      retrospective survival analysis in twenty-three patients.

PMID- 28429526
TI  - Sll1783, a monooxygenase associated with polysaccharide processing in the
      unicellular cyanobacterium Synechocystis PCC 6803.
AB  - Cyanobacteria play a pivotal role as the primary producer in many aquatic
      ecosystems. The knowledge on the interacting processes of cyanobacteria with its
      environment - abiotic and biotic factors - is still very limited. Many potential
      exocytoplasmic proteins in the model unicellular cyanobacterium Synechocystis PCC
      6803 have unknown functions and their study is essential to improve our
      understanding of this photosynthetic organism and its potential for biotechnology
      use. Here we characterize a deletion mutant of Synechocystis PCC 6803,
      Deltasll1783, a strain that showed a remarkably high light resistance which is
      related with its lower thylakoid membrane formation. Our results suggests Sll1783
      to be involved in a mechanism of polysaccharide degradation and uptake and we
      hypothesize it might function as a sensor for cell density in cyanobacterial
      cultures.

PMID- 28429527
TI  - Balancing health care education and patient care in the UK workplace: a realist
      synthesis.
AB  - CONTEXT: Patient care activity has recently increased without a proportionate
      rise in workforce numbers, impacting negatively on health care workplace
      learning. Health care professionals are prepared in part by spending time in
      clinical practice, and for medical staff this constitutes a contribution to
      service. Although stakeholders have identified the balance between health care
      professional education and patient care as a key priority for medical education
      research, there have been very few reviews to date on this important topic.
      METHODS: We conducted a realist synthesis of the UK literature from 1998 to
      answer two research questions. (1) What are the key workplace interventions
      designed to help achieve a balance between health care professional education and
      patient care delivery? (2) In what ways do interventions enable or inhibit this
      balance within the health care workplace, for whom and in what contexts? We
      followed Pawson's five stages of realist review: clarifying scope, searching for
      evidence, assessment of quality, data extraction and data synthesis. RESULTS: The
      most common interventions identified for balancing health care professional
      education and patient care delivery were ward round teaching, protected learning
      time and continuous professional development. The most common positive outcomes
      were simultaneous improvements in learning and patient care or improved learning
      or improved patient care. The most common contexts in which interventions were
      effective were primary care, postgraduate trainee, nurse and allied health
      professional contexts. By far the most common mechanisms through which
      interventions worked were organisational funding, workload management and
      support. CONCLUSION: Our novel findings extend existing literature in this
      emerging area of health care education research. We provide recommendations for
      the development of educational policy and practice at the individual,
      interpersonal and organisational levels and call for more research using realist
      approaches to evaluate the increasing range of complex interventions to help
      balance health care professional education and patient care delivery.

PMID- 28429528
TI  - Use of adenosine to shorten the post ablation waiting period for cavotricuspid
      isthmus-dependent atrial flutter.
AB  - BACKGROUND: Dormant conduction unmasked by adenosine predicts clinical
      recurrences of cavotricuspid isthmus (CTI) dependent atrial flutter following
      catheter ablation. Conventional practice involves a waiting period of 20 to 30
      minutes after achievement of a bidirectional line of block (BDB) to monitor for
      recovery of conduction. OBJECTIVE: Assess whether abolition of dormant conduction
      with adenosine immediately after CTI ablation and BDB can predict the lack of CTI
      conduction recovery during the following 30 minutes. METHODS: Consecutive
      patients undergoing catheter ablation for CTI-dependent atrial flutter were
      studied. Following the completion of CTI ablation and documentation of BDB,
      adenosine (>=12 mg IV) was administered immediately. In cases of dormant
      conduction, the CTI was ablated again until its abolition. After the achievement
      of BDB without dormant conduction, spontaneous CTI reconnection during the
      following 30 minutes and dormant conduction with adenosine at 30 minutes were
      evaluated. RESULTS: A CTI block was achieved in 171 patients. Nine patients
      (5.3%) had dormant conduction across the CTI immediately after ablation and BDB,
      and required further ablation. Two patients (1.2%) had subsequent spontaneous
      time-dependent reconnection within 30 minutes. Two other patients (1.2%)
      developed late dormant conduction with adenosine at 30 minutes. All 4 patients
      underwent further ablation. CONCLUSION: A negative adenosine challenge
      immediately after CTI ablation with bidirectional block, or after abolition of
      dormant conduction with further ablation, strongly predicted the absence of
      subsequent spontaneous reconnection within 30 minutes. Based on these results,
      the conventional waiting period is unnecessary in 97.6% patients without dormant
      conduction after CTI-dependent flutter ablation.

PMID- 28429530
TI  - Retraction: 'Each of the chloroplast potassium efflux antiporters affects
      photosynthesis and growth of fully developed Arabidopsis rosettes under short-day
      photoperiod' by Somnath Dana, Andrei Herdean, Bjorn Lundin and Cornelia Spetea.

PMID- 28429529
TI  - Impaired left atrial function predicts inappropriate shocks in primary prevention
      implantable cardioverter-defibrillator candidates.
AB  - INTRODUCTION: Inappropriate implantable cardioverter-defibrillator (ICD) shocks,
      commonly caused by atrial fibrillation (AF), are associated with an increased
      mortality. Because impaired left atrial (LA) function predicts development of AF,
      we hypothesized that impaired LA function predicts inappropriate shocks beyond a
      history of AF. METHODS AND RESULTS: We prospectively analyzed the association
      between LA function and incident inappropriate shocks in primary prevention ICD
      candidates. In the Prospective Observational Study of ICD (PROSE-ICD), we
      assessed LA function using tissue-tracking cardiac magnetic resonance (CMR) prior
      to ICD implantation. A total of 162 patients (113 males, age 56 +/- 15 years)
      were included. During the mean follow-up of 4.0 +/- 2.9 years, 26 patients (16%)
      experienced inappropriate shocks due to AF (n = 19; 73%), supraventricular
      tachycardia (n = 5; 19%), and abnormal sensing (n = 2; 8%). In univariable
      analyses, inappropriate shocks were associated with AF history prior to ICD
      implantation, age below 70 years, QRS duration less than 120 milliseconds, larger
      LA minimum volume, lower LA stroke volume, lower LA emptying fraction, impaired
      LA maximum and preatrial contraction strains (Smax and SpreA ), and impaired LA
      strain rate during left ventricular systole and atrial contraction (SRs and SRa
      ). In multivariable analysis, impaired Smax (hazard ratio [HR]: 0.96, P = 0.044),
      SpreA (HR: 0.94, P = 0.030), and SRa (HR: 0.25, P < 0.001) were independently
      associated with inappropriate shocks. The receiver-operating characteristics
      curve showed that SRa improved the predictive value beyond the patient
      demographics including AF history (P = 0.033). CONCLUSION: Impaired LA function
      assessed by tissue-tracking CMR is an independent predictor of inappropriate
      shocks in primary prevention ICD candidates beyond AF history.

PMID- 28429531
TI  - Sugar enrichment provides evidence for a role of nitrogen fixation in coral
      bleaching.
AB  - The disruption of the coral-algae symbiosis (coral bleaching) due to rising sea
      surface temperatures has become an unprecedented global threat to coral reefs.
      Despite decades of research, our ability to manage mass bleaching events remains
      hampered by an incomplete mechanistic understanding of the processes involved. In
      this study, we induced a coral bleaching phenotype in the absence of heat and
      light stress by adding sugars. The sugar addition resulted in coral symbiotic
      breakdown accompanied by a fourfold increase of coral-associated microbial
      nitrogen fixation. Concomitantly, increased N:P ratios by the coral host and
      algal symbionts suggest excess availability of nitrogen and a disruption of the
      nitrogen limitation within the coral holobiont. As nitrogen fixation is similarly
      stimulated in ocean warming scenarios, here we propose a refined coral bleaching
      model integrating the cascading effects of stimulated microbial nitrogen
      fixation. This model highlights the putative role of nitrogen-fixing microbes in
      coral holobiont functioning and breakdown.

PMID- 28429532
TI  - Neu1 sialidase interacts with perilipin 1 on lipid droplets and inhibits
      lipolysis in 3T3-L1 adipocytes.
AB  - Fatty acids are stored within adipocytes in lipid droplets (LDs) as
      triacylglycerol (TG), which is converted to free fatty acid (FFA) and glycerol
      via lipolysis. Increased plasma FFA levels in obesity are associated with several
      clinical conditions. We previously found that Neu1 activity is aberrant in the
      epididymal fat and liver of obese and diabetic mice. Here, we examined
      involvement of Neu1 in lipolysis in 3T3-L1 adipocytes. Small interfering RNA
      against Neu1 was introduced into adipocytes, and glycerol concentrations were
      measured in the culture medium. We then assessed the effects of Neu1 knockdown on
      lipolytic protein expression and phosphorylation, as well as interactions between
      perilipin 1 (Plin1) and hormone-sensitive lipase (HSL) after isoproterenol (IS)
      stimulation. Interactions between Neu1 and Plin1 were analyzed by
      immunoprecipitation and immunofluorescent imaging using adipocytes transfected
      with pCMV6-mNeu1-myc-DYKDDDDK (mNeu1DDK). Neu1 knockdown increased glycerol
      concentrations in culture media and Plin1 phosphorylation in whole lysates of IS
      stimulated cells. Neu1 knockdown increased interaction between Plin1 and HSL
      after IS stimulation whereas that between Neu1 and Plin1 on LD observed under
      basal conditions was lost. These results suggest that Neu1 inhibits lipolysis
      induced by beta-adrenergic stimulation in adipocytes via interactions with Plin1
      on LD.

PMID- 28429534
TI  - Role of microbes in maternal and child health - Friends or foes?

PMID- 28429533
TI  - Impact of adverse drug events and treatment satisfaction on patient adherence
      with antihypertensive medication - a study in ambulatory patients.
AB  - AIMS: The aim of the present study was to evaluate the impact of adverse drug
      events (ADEs) and treatment satisfaction on antihypertensive medication
      adherence. METHODS: A cross-sectional study was conducted in six public hospitals
      in Ethiopia. We included adult ambulatory patients on antihypertensive
      medication. Adherence was measured using the eight-point Morisky Medication
      Adherence Scale, which categorizes as low (0-5), medium (6-7) and high (8)
      adherence. Treatment satisfaction was measured using the Treatment Satisfaction
      Questionnaire for Medication (TSQM) version 1.4, which included questions about
      ADEs. Data were analysed using generalized ordered logistic regression with 95%
      confidence intervals (CIs). RESULTS: We included 925 out of 968 patients.
      Overall, 42% of patients scored low, 37% medium and 21% high adherence.
      Satisfaction with treatment was low, with a mean (standard deviation) TSQM score
      for global satisfaction of 51 (14). A total of 193 (21%) patients experienced 421
      ADEs - mainly dyspeptic symptoms (12%), headache (11%) and cough (11).
      Experiencing more ADEs reduced the odds of being adherent [low vs. medium/high:
      odds ratio (OR) OR1 0.77 (95% CI 0.67, 0.89), and low/medium vs. high: OR2 0.55
      (05% CI 0.41, 0.73)]. Being more satisfied increased the odds of being adherent
      [low vs. medium/high: OR1 1.02 (95% CI 1.01, 1.03)]. Taking medication >1 year
      [OR1 = 2 , 0.60 (95% CI 0.43, 0.83)] and taking calcium channel blockers [OR1 = 2
      0.71 (95% CI 0.54, 0.92)] decreased the odds for both low vs. medium/high and
      low/medium vs. high adherence. CONCLUSIONS: Only one in five patients reported
      perfect (high) adherence to their antihypertensive treatment regimen.
      Experiencing ADEs and being dissatisfied with treatment were associated with
      lower adherence. In addition to addressing treatment satisfaction and drug safety
      in first-world countries, these should also be addressed in resource-poor
      settings, within patient consultations, to enhance adherence.

PMID- 28429535
TI  - A cross-circulated bicephalic model of head transplantation.
AB  - AIMS: A successful cephalosomatic anastomosis ("head transplant") requires, among
      others, the ability to control long-term immune rejection and avoidance of
      ischemic events during the head transference phase. We developed a bicephalic
      model of head transplantation to study these aspects. METHODS AND RESULTS: The
      thoracic aorta and superior vena cava of a donor rat were anastomosed with the
      carotid artery and extracorporeal veins of a recipient rat by vascular grafts.
      Before thoracotomy in the donor rat, the axillary artery and vein of the donor
      were connected to the carotid and the extracranial vein of the third rat through
      a silicone tube. The silicone tube was passed through a peristaltic pump to
      ensure donor brain tissue blood supply. There is no ischemia reperfusion injury
      in donor brain tissue analyzed by electroencephalogram. Postoperative donor has
      pain reflex and corneal reflex. CONCLUSIONS: Peristaltic pump application can
      guarantee the blood supply of donor brain tissue per unit time, while the
      application of temperature change device to the silicone tube can protect the
      brain tissue hypothermia, postoperative experimental data show that there is no
      brain tissue ischemia during the whole operation. The application of vascular
      grafting can also provide the possibility of long-term survival of the model.

PMID- 28429536
TI  - alpha-Mangostin decreases beta-amyloid peptides production via modulation of
      amyloidogenic pathway.
AB  - AIMS: beta-amyloid (Abeta) aggregation and deposition play a central role in the
      pathogenic process of Alzheimer's disease (AD). alpha-Mangostin (alpha-M), a
      polyphenolic xanthone, have been shown to dissociate Abeta oligomers. In this
      study, we further investigated the effect of alpha-M on Abeta production and its
      molecular mechanism. METHODS: The Abeta and soluble amyloid precursor protein
      alpha (sAPPalpha) in culture medium of cortical neurons were measured by ELISA.
      The activities of alpha-, beta-, and gamma-secretases were assayed, and the
      interaction between alpha-M and beta- or gamma-secretases was simulated by
      molecular docking. RESULTS: alpha-M significantly decreased Abeta40 and Abeta42
      production. alpha-M did not affect the expression of enzymes involved in
      nonamyloidogenic and amyloidogenic pathways, but significantly decreased the
      activities of beta-secretase and likely gamma-secretase with IC50 13.22 nmol.L-1
      and 16.98 nmol.L-1 , respectively. Molecular docking demonstrated that alpha-M
      interacted with beta-site amyloid precursor protein cleaving enzyme 1 and
      presenilin 1 to interfere with their active sites. CONCLUSIONS: Our data
      demonstrate that alpha-M decreases Abeta production through inhibiting activities
      of beta-secretase and likely gamma-secretase in the amyloidogenic pathway. The
      current data together with previous study indicated that alpha-M could be a novel
      neuroprotective agent through intervention of multiple pathological processes of
      AD.

PMID- 28429537
TI  - Preliminary findings on the safety of 1.5 and 3 Tesla magnetic resonance imaging
      in cardiac pacemaker patients.
AB  - INTRODUCTION: Modern pacemakers are designed to allow patients to undergo
      magnetic resonance imaging (MRI) under a set of specific conditions. Aim of this
      study is to provide confirmatory evidence of safety and performance of a new
      pacing system (ImageReadyTM, Boston Scientific) in patients undergoing 1.5 and 3T
      MRI. METHODS AND RESULTS: Two prospective, nonrandomized, single-arm studies were
      designed to provide confirmatory data of no impact of MRI on device function,
      lead parameters, and patient conditions in subjects implanted with the system
      undergoing a clinically non-indicated 1.5T and 3T MRI, respectively. Device
      measurements were done within 1 hour before and after the scan and at 1 month
      follow-up. Thirty-two subjects underwent MRI visit (17 subjects with 1.5T MRI and
      15 subjects with 3T MRI). There were no unanticipated adverse effects related to
      the pacemaker. Device measurements taken pre- and post-MRI scan did not show any
      clinical relevant change that could indicate an effect of the MRI on the device
      or at the lead-tissue interface (RV threshold change: 0.01 +/- 0.13 V, P = 0.60;
      RA threshold change: 0.01 +/- 0.11 V, P = 0.53; R wave change: -0.44 +/- 1.73 mV,
      P = 0.36; R wave change: 0.12 +/- 1.67 mV, P = 0.73), with data confirmed at 1
      month follow-up visit. CONCLUSION: The study documented safety of the pacing
      system in the 1.5T and 3T MRI environment by showing no adverse events related to
      device or MRI scan. Additional data are required to cover the more complex
      scenarios involving different diagnostic needs, conditions of use, clinical
      conditions, and new emerging technologies.

PMID- 28429539
TI  - What should the optimal intrauterine pressure be during outpatient diagnostic
      hysteroscopy? A randomized comparative study.
AB  - AIM: The aim of this study was to evaluate and compare lower and higher uterine
      filling pressures during outpatient diagnostic hysteroscopy. METHODS: One hundred
      and seventy-five women eligible for outpatient diagnostic hysteroscopy were
      included in this randomized double blind comparative study. The subjects were
      randomized into two groups. Group 1 (n = 80) underwent surgery with lower
      intrauterine filling pressures (30, 40, and 50 mmHg) and group 2 (n = 81)
      underwent surgery with higher filling pressures (70, 80, and 100 mmHg). The
      primary outcome measure was adequate visibility during the procedure. The
      secondary outcome measure was pain perceived by the patient during and 30 min
      after the procedure. RESULTS: In total, 161 patients completed the trial. Group 2
      had significantly higher adequate visibility than group 1 (71/80, 88.75% in group
      1 and 79/81, 97.5% in group 2, P = 0.008). There was a trend toward increase in
      pain scores with higher pressures during the procedure. However, there were no
      significant differences between the two groups in terms of visual analog scale
      pain scores measured 30 min after the procedure. CONCLUSION: Lower uterine
      filling pressure was associated with lower pain scores with a higher trend
      towards inadequate visibility. It appears that higher filling pressure can be
      used for performing office hysteroscopy, but it is associated with higher pain
      scores.

PMID- 28429538
TI  - Finding a partner in the ocean: molecular and evolutionary bases of the response
      to sexual cues in a planktonic diatom.
AB  - Microalgae play a major role as primary producers in aquatic ecosystems. Cell
      signalling regulates their interactions with the environment and other organisms,
      yet this process in phytoplankton is poorly defined. Using the marine planktonic
      diatom Pseudo-nitzschia multistriata, we investigated the cell response to cues
      released during sexual reproduction, an event that demands strong regulatory
      mechanisms and impacts on population dynamics. We sequenced the genome of P.
      multistriata and performed phylogenomic and transcriptomic analyses, which
      allowed the definition of gene gains and losses, horizontal gene transfers,
      conservation and evolutionary rate of sex-related genes. We also identified a
      small number of conserved noncoding elements. Sexual reproduction impacted on
      cell cycle progression and induced an asymmetric response of the opposite mating
      types. G protein-coupled receptors and cyclic guanosine monophosphate (cGMP) are
      implicated in the response to sexual cues, which overall entails a modulation of
      cell cycle, meiosis-related and nutrient transporter genes, suggesting a fine
      control of nutrient uptake even under nutrient-replete conditions. The
      controllable life cycle and the genome sequence of P. multistriata allow the
      reconstruction of changes occurring in diatoms in a key phase of their life
      cycle, providing hints on the evolution and putative function of their genes and
      empowering studies on sexual reproduction.

PMID- 28429540
TI  - Silencing of astrocyte elevated gene-1 inhibits proliferation and migration of
      melanoma cells and induces apoptosis.
AB  - Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte
      elevated gene-1 (AEG-1), a downstream target of Ras and c-Myc, has been
      implicated in the development of multiple tumours, but its role in melanoma
      remains unclear. In the present study, the role of AEG-1 in melanoma was explored
      through AEG-1 silencing. Our results showed that silencing AEG-1 inhibited the
      proliferation of melanoma cells, induced cell cycle arrest, and reduced levels of
      cyclin A, cyclin B, cyclin D1, cyclin E, and cyclin-dependent kinase 2. AEG
      1silencing also induced apoptosis in melanoma cells and altered the levels of
      cleaved caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein.
      Moreover, silencing AEG-1 suppressed the migration and invasion of melanoma
      cells, reduced the expressions and activities of matrix metallopeptidase (MMP)-2
      and MMP-9, and inhibited the activation of the Wnt/beta-catenin signalling
      pathway in melanoma cells. Furthermore, in vivo experiments revealed that AEG-1
      silencing inhibited the growth of melanoma xenografts in nude mice. In summary,
      our study demonstrates an oncogenic role of AEG-1 in melanoma and suggests that
      AEG-1 may serve as a potential therapeutic target in the treatment of melanoma.

PMID- 28429541
TI  - Toward Practical High-Energy Batteries: A Modular-Assembled Oval-Like Carbon
      Microstructure for Thick Sulfur Electrodes.
AB  - The modular assembly of microstructures from simple nanoparticles offers a
      powerful strategy for creating materials with new functionalities. Such
      microstructures have unique physicochemical properties originating from
      confinement effects. Here, the modular assembly of scattered ketjen black
      nanoparticles into an oval-like microstructure via double "Fischer
      esterification," which is a form of surface engineering used to fine-tune the
      materials surface characteristics, is presented. After carbonization, the oval
      like carbon microstructure shows promise as a candidate sulfur host for the
      fabrication of thick sulfur electrodes. Indeed, a specific discharge capacity of
      8.417 mAh cm-2 at 0.1 C with a high sulfur loading of 8.9 mg cm-2 is obtained.
      The large-scale production of advanced lithium-sulfur battery pouch cells with an
      energy density of 460.08 Wh kg-1 @18.6 Ah is also reported. This work provides a
      radically different approach for tuning the performance of a variety of surfaces
      for energy storage materials and biological applications by reconfiguring
      nanoparticles into desired structures.

PMID- 28429542
TI  - Study of the wearable cardioverter defibrillator in advanced heart-failure
      patients (SWIFT).
AB  - INTRODUCTION: The wearable cardioverter defibrillator (WCD) may allow
      stabilization until reassessment for an implantable cardioverter defibrillator
      (ICD) among high-risk heart failure (HF) patients. However, there are limited
      data on the WCD benefit in the acute decompensated HF setting. METHODS AND
      RESULTS: The Study of the Wearable Cardioverter Defibrillator in Advanced Heart
      Failure Patients (SWIFT) was a prospective clinical trial carried out at two
      medical centers. Patients hospitalized with advanced HF symptoms and reduced left
      ventricular ejection function (LVEF) were enrolled and prescribed a WCD prior to
      discharge for a total of 3 months. Outcome measures included arrhythmic events,
      WCD discharge, and death. Study patients (n = 75, mean age 51 +/- 14 years, 31%
      women) had a mean LVEF of 21.5 +/- 10.4%. Non-ischemic cardiomyopathy was present
      in 66% of patients. The median WCD wearing time was 59 (interquartile range 17
      97) days, and 80% of patients wore the device >50% of daily hours. WCD
      interrogations showed a total of 8 arrhythmic events in 5 patients, including 3
      nonsustained or self-terminating ventricular tachycardia (VT) events, and one
      polymorphic VT successfully terminated by the WCD. None of the patients died
      while wearing the device and no inappropriate device therapies occurred. Upon
      termination of treatment with the WCD, 21 patients (28%) received an ICD. At 3
      years, the cumulative death rate was 20% in the ischemic and 21% in non-ischemic
      cardiomyopathy patients. CONCLUSION: A management strategy incorporating the WCD
      can be safely used to bridge the decision regarding the need for ICD implantation
      in high-risk patients with advanced HF.

PMID- 28429543
TI  - On the formation of smaller p-block endohedral fullerenes: Bonding analysis in
      the E@C20 (E = Si, Ge, Sn, Pb) series from relativistic DFT calculations.
AB  - Experimentally characterized endohedral metallofullerenes are of current interest
      in expanding the range of viable fullerenic structures and their applications.
      Smaller metallofullerenes, such as M@C28 , show that several d- and f-block
      elements can be efficiently confined in relatively small carbon cages. This
      article explores the potential capabilities of the smallest fullerene cage, that
      is, C20 , to encapsulate p-block elements from group 14, that is, E = Si, Ge, Sn,
      and Pb. Our interest relates to the bonding features and optical properties
      related to E@C20 . The results indicate both s- and p-type concentric bonds, in
      contrast to the well explored endohedral structures encapsulating f-block
      elements. Our results suggest the E@C20 series to be a new family of viable
      endohedral fullerenes. In addition spectroscopic properties related to electron
      affinity, optical, and vibrational were modeled to gain further information
      useful for characterization. Characteristic optical patterns were studied
      predicting a distinctive first peak located between 400 and 250 nm, which is red
      shifted going to the heavier encapsulated Group 14 atoms. Electron affinity
      properties expose different patterns useful to differentiate the hollow C20
      fullerene to the proposed p-block endohedral counterparts. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28429544
TI  - An Innovative Cooling Jacket to Combat Heat Intolerance in Children with
      Anhidrosis.
AB  - Hyperthermia and heat intolerance are distressing symptoms in patients with
      anhidrosis. Body cooling devices are an integral part of management of these
      patients. A cooling jacket made from easily available materials has been invented
      for a girl with congenital insensitivity to pain and anhidrosis with severe heat
      intolerance. This innovative cooling jacket may be helpful for anhidrotic
      children in resource-poor situations.

PMID- 28429545
TI  - Do the benefits of using calcitriol and other vitamin D receptor activators in
      patients with chronic kidney disease outweigh the harms?
AB  - The primary indication for administration of calcitriol or other vitamin D
      receptor activators (VDRA) in chronic kidney disease (CKD) is secondary
      hyperparathyroidism (SHPT). Prevention and treatment of SHPT appears important,
      as imbalances in mineral metabolism are associated with renal osteodystrophy, and
      higher parathyroid hormone (PTH) levels are associated with increased rates of
      mortality and morbidity in CKD patients. There is, however, a lack of controlled
      trial data that show lowering PTH with calcitriol/VDRA equates to improved
      clinical outcomes. Recent randomized controlled trials have concentrated on
      potential benefits of calcitriol/VDRA on cardiovascular outcomes and reduction of
      proteinuria and on possible differences between calcitriol and the various VDRA.
      Several systematic reviews and meta-analyses have also been published, evaluating
      the benefits and harms of calcitriol/VDRA. Concerns have been raised about the
      effectiveness of calcitriol/VDRA for suppression of SHPT in the CKD stages 3-5
      population, as well as potential adverse outcomes such as hypercalcaemia and
      elevation in FGF23 levels, suggesting their routine use to treat SHPT in the pre
      dialysis CKD population may not be favourable. Conversely, concerns still exist
      about the wide PTH range in advanced CKD, and that high values may negatively
      impact bone quality, result in the progression of parathyroid hyperplasia and
      decrease the effectiveness of treatments to reduce PTH. We discuss the current
      controversies relating to the challenges in the management of SHPT in patients
      with CKD stages 3-5 and the need for more evidence to determine the efficacy or
      harm of using calcitriol/VDRA in this population.

PMID- 28429546
TI  - Should nephrologists consider vascular calcification screening?
AB  - Vascular calcification (VC) has been widely discussed over the last few decades
      and is associated with significant morbidity and mortality among patients with
      chronic kidney disease. Importantly, these patients have premature and rapidly
      progressive calcification when compared with the general population. VC is an
      active and complex process that is closely regulated by a growing list of
      inducers and inhibitors. VC can be detected using several non-invasive modalities
      including plain radiography, echocardiogram and computed tomography scans.
      However, the usefulness of these imaging measurements to capture treatment
      effects may be limited. Routine screening and monitoring for progression of VC
      remains highly debatable.

PMID- 28429547
TI  - The use of bone turnover markers in chronic kidney disease-mineral and bone
      disorders.
AB  - Bone turnover markers assist in fracture risk prediction, management and
      monitoring of osteoporosis in patients without chronic kidney disease (CKD). The
      use in CKD-mineral bone disorder (MBD) has been limited as many of these markers
      and breakdown products are renally excreted, including the most commonly used and
      well standardized procollagen type I N propeptide and C-terminal cross-linking
      telopeptide of type I collagen. Of the markers unaffected by renal function, bone
      specific alkaline phosphatase is associated with mortality and fracture rate in
      CKD subjects and is now available on several automated analysers. When used in
      combination with PTH, bone specific alkaline phosphatase as a bone formation
      marker correlated well with bone biopsy histomorphometry in predicting adynamic
      bone disease. Tartrate-resistant acid phosphatase 5b is a resorption marker that
      is under development for automation. Both high and low bone turnover in CKD-MBD
      patients are associated with increased fracture and mortality risk. Bone biopsy
      as the gold standard to differentiate between adynamic bone disease and osteitis
      fibrosa is limited by availability and cost. Appropriate use of bone turnover
      markers is vital in the decision to commence anti-resorptive agents, and to
      monitor efficacy in order to avoid over suppression of bone turnover, which may
      lead to stress fractures. Further efforts are required to develop markers
      unaffected by renal function with standardized cut-off values and fracture as
      well as vascular calcification end-points.

PMID- 28429548
TI  - Is serum phosphate a useful target in patients with chronic kidney disease and
      what is the role for dietary phosphate restriction?
AB  - A complex system of endocrine and paracrine signals exists to control phosphate
      balance. Dysregulation of these systems in patients with chronic kidney disease
      has serious clinical consequences. Whilst observational studies have shown
      associations between higher serum phosphate levels and poor clinical outcomes,
      the direction of causality has not been demonstrated. Whether there is a target
      level of serum phosphate remains controversial and no randomized trials to date
      have proved that strategies to lower extracellular phosphate actually improve
      clinical outcomes. Serum phosphate provides only a partial measure of overall
      phosphate balance and, importantly, calcification risk. Changes in dietary
      phosphate may be a modifiable source of phosphate in humans, although better
      methods for assessment of dietary phosphate intake are required. Individuals
      consume large amounts of phosphate in processed foods, rich in phosphate
      additives, and there is interest in restricting dietary phosphate as a matter of
      public health, although the association between dietary phosphate and serum
      phosphate is modest at best. Interventional studies are needed to provide
      supportive evidence of any potential advantages of dietary phosphate restriction
      before such measures can be recommended.

PMID- 28429549
TI  - Is there a practical role for a virtual bone biopsy using high-resolution imaging
      of bone in patients with chronic kidney disease?
AB  - Renal osteodystrophy (ROD) refers to alterations in bone turnover,
      mineralisation, mass and microarchitecture in patients with chronic kidney
      disease (CKD) and represents the skeletal component of 'CKD-mineral and bone
      disorder'. Changes in bone structure lead to impaired bone quality, compromised
      bone strength and increased susceptibility to fractures with associated
      significant morbidity, mortality and financial cost. Diagnosis and management of
      ROD is hindered by the inadequacy of currently available diagnostic methods to
      interpret the complex pathophysiology. Bone biopsy, the perceived gold standard
      test to assess ROD, is invasive and suboptimal for disease screening and
      management in routine clinical practice. High-resolution imaging, such as high
      resolution peripheral quantitative computed tomography and high-resolution
      magnetic resonance imaging provide accurate non-invasive quantification of bone
      microarchitecture and facilitate assessment of mechanical competence of bone,
      correlating with skeletal fragility. We discuss the potential for these imaging
      techniques in patients with CKD to provide quantification and assessment of bone
      structure and strength. When used in conjunction with serum biomarkers, these
      investigative tools may provide a non-invasive diagnostic virtual bone biopsy.

PMID- 28429550
TI  - Parathyroid hormone targets in chronic kidney disease and managing severe
      hyperparathyroidism.
AB  - Appropriate targets for parathyroid hormone (PTH) in patients with chronic kidney
      disease (CKD) stages 3-5D are controversial, as are the means by which these
      targets might be achieved. Secondary hyperparathyroidism is linked to symptoms
      like bone pain and itch, in addition to less clinically overt issues like bone
      fragility as well as vascular and soft tissue calcification which may lead to
      adverse hard endpoints, particularly fracture and death. Recognized therapies for
      managing a rising PTH include vitamin D analogues, with or without calcimimetic
      (where available), in addition to management of serum mineral concentrations with
      diet, binders and dialysis. Despite these interventions, many patients eventually
      develop refractory metabolic abnormalities of severe hyperparathyroidism (HPT).
      Treatment decisions in severe HPT in Australia previously centred around whether
      to perform parathyroidectomy or use calcimimetics in combination with calcitriol
      (or its analogues) with goals of symptom relief, fracture reduction and reducing
      vascular risk. The decision to remove Pharmaceutical Benefits Scheme
      reimbursement for the calcimimetic cinacalcet during 2015, means that
      parathyroidectomy has now become the only treatment likely to benefit most
      patients with severe HPT who are medically fit for operative intervention.
      Although improvements in care are apparent for patients with CKD, there remains
      an urgent need for basic science and large international trials to inform better
      ways to manage HPT.

PMID- 28429551
TI  - The role of calcium and non calcium-based phosphate binders in chronic kidney
      disease.
AB  - Rising levels of serum phosphate occur late in the course of chronic kidney
      disease (CKD) and have been easy targets for nephrologists to treat using
      phosphate binding drugs, as well as fertile ground for the pharmaceutical
      industry, for meta-analysis and for the earnest pontifications of guideline
      writers. Unfortunately, the evidence does little to support this focus, which
      might be better applied to earlier, adaptive hormonal changes, and to phosphate
      balance rather than serum phosphate levels. Nevertheless, phosphate binders are
      ubiquitously prescribed to patients on dialysis, and often prescribed to patients
      with earlier stages of CKD; for which there is no evidence of benefit and some
      evidence that calcium-based binders (CBBs) and possibly non-CBBs may cause more
      harm than placebo. For patients on dialysis, observational studies suggest that
      phosphate binder use may reduce mortality. Meta-analyses report reduced
      hypercalcaemia for non-CBBs versus CBBs, and compared with CBBs sevelamer has
      been reported to significantly reduce vascular calcification progression and, in
      some but not all studies, overall mortality. However, limitations include study
      heterogeneity. For patients on dialysis, CBBs appear to have no advantages over
      the non-CBBs, apart from lower cost. In general, it seems prudent to avoid
      prescribing calcium-based drugs to patients who are pre-dialysis, and to use non
      CBBs preferentially in CKD stage 5D. Current draft Kidney Disease Improving
      Global Outcomes guidelines suggest that CBB dosage be minimized in CKD stages 3
      to 5D.

PMID- 28429553
TI  - Conclusions and future directions: 'The known unknowns ....'

PMID- 28429552
TI  - Overview of bone microstructure, and treatment of bone fragility in chronic
      kidney disease.

PMID- 28429554
TI  - Is there a practical role for bone biopsy in chronic kidney disease?
AB  - Bone biopsy is currently the only means to accurately assess renal osteodystrophy
      and responses to therapeutic interventions. With sedation, the technique is
      relatively painless, and complications are uncommon. Bone biopsy should be
      considered when the aetiology of symptoms or biochemical abnormalities is in
      question, and results may lead to changes in therapy. Although it remains prudent
      to use antiresorptive drugs cautiously in patients with chronic kidney disease
      (CKD) stages 3a-4 and low bone mineral density, bone biopsy may not be warranted
      before commencing therapy in these patients. Histomorphometric indices adopted
      for bone biopsy assessment are turnover (T), mineralisation (M) and volume (V).
      Often, only measurements of trabecular bone are reported; however, marked
      cortical changes are common in CKD and may be critical to bone structure and
      integrity. MicroCT of bone biopsies can rapidly assess static parameters and
      provides information on the cortical and trabecular compartments that may
      influence management. Limitations of bone biopsy include the time required for
      pre-biopsy tetracycline labelling and sample processing, and a paucity of
      facilities to process and report samples. Patients with CKD may not respond
      predictably to treatments, and because the biopsy sample is illustrative of
      activity at only one skeletal site and one point in time, assessment of real-time
      laboratory trends is always required. Optimally, we need a non-invasive 'virtual
      bone biopsy' that provides information for initiating and monitoring therapy.
      However, bone biopsy is the current standard by which the accuracy of
      investigational imaging techniques, hormonal values and biochemical turnover
      markers are judged.

PMID- 28429556
TI  - The burden of fractures, vascular pathology and mortality in chronic kidney
      disease-mineral and bone disorders.

PMID- 28429555
TI  - Management of mineral and bone disorders in renal transplant recipients.
AB  - The management of post-transplantation bone disease is a complex problem that
      remains under-appreciated in clinical practice. In these patients, pre-existing
      metabolic bone disorder is further impacted by the use of immunosuppressive
      medications (glucocorticoids and calcineurin-inhibitors), variable post
      transplantation renal allograft function and post-transplantation diabetes
      mellitus. The treatment of post-transplantation bone loss should begin pre
      transplantation. All patients active on transplant waiting lists should be
      screened for bone disease. Patients should also be encouraged to take
      preventative measures against osteoporosis such as regular weight-bearing
      exercise, smoking cessation and reducing alcohol consumption. Biochemical
      abnormalities of disordered mineral metabolism should be corrected prior to
      transplantation wherever possible, and because these abnormalities commonly
      persist, post transplant hypophosphatemia, persistent hyperparathyroidism and low
      vitamin D levels should be regularly monitored and treated. Bone loss is greatest
      in the first 6-12 months post-transplantation, during which period any
      intervention is likely to be of greatest benefit. There is strong evidence that
      bisphosphonates prevent post-transplantation bone loss; however, data are lacking
      that this clearly extends to a reduction in fracture incidence. Denosumab is a
      potential alternative to vitamin D receptor agonists and bisphosphonates in
      reducing post-transplantation bone loss; however, further studies are needed to
      demonstrate its safety in patients with a significantly reduced estimated
      glomerular filtration rate. Clinical judgement remains the cornerstone of this
      complex clinical problem, providing a strong rationale for the formation of
      combined endocrinology and nephrology clinics to treat patients with Chronic
      Kidney Disease-Mineral and Bone Disorder, before and after transplantation.

PMID- 28429557
TI  - Use of dual energy X-ray absorptiometry, the trabecular bone score and
      quantitative computed tomography in the evaluation of chronic kidney disease
      mineral and bone disorders.
AB  - In subjects with chronic kidney disease (CKD) who suffer a minimal trauma
      fracture, the problem is to differentiate between osteoporosis and the various
      forms of renal bone disease associated with CKD-mineral and bone disorder. This
      problem is exacerbated by the fact that renal osteodystrophy may coexist with
      osteoporosis. The World Health Organization's bone mineral density (BMD) criteria
      for osteopenia ( -2.5 < T-score < -1.0) and osteoporosis (a T-score <= -2.5) may
      be used in patients with CKD stages 1-3. In CKD stages 4-5, BMD by dual-energy X
      ray absorptiometry (DXA) is less predictive and may underestimate fracture risk.
      The development of absolute fracture risk (AFR) algorithms, such as FRAX(r) and
      the Garvan absolute fracture risk calculator, to predict risk of fracture over a
      given time (usually 10 years) aims to incorporate non-BMD risk factors into the
      clinical assessment. FRAX(r) has been shown to be useful to assess fracture risk
      in CKD but may underestimate fracture risk in advanced CKD. The trabecular bone
      score is a measure of grey scale homogeneity obtained from spine DXA, which
      correlates to trabecular microarchitecture and is an independent risk factor for
      fracture. Recent data demonstrate the potential utility of the trabecular bone
      score adjustment of AFR through the FRAX(r) algorithm in subjects with CKD.
      Parameters of bone microarchitecture using peripheral quantitative computed
      tomography (pQCT) or high-resolution pQCT are also able to discriminate fracture
      status in subjects with CKD. However, there are at present no convincing data
      that the addition of pQCT or high-resolution pQCT parameters to DXA BMD improves
      fracture discrimination. More advanced estimates of bone strength derived from
      measurements of micro-architecture, by QCT-derived finite element analysis may be
      incorporated into AFR algorithms in the future.

PMID- 28429558
TI  - Is there a role or target value for nutritional vitamin D in chronic kidney
      disease?
AB  - Vitamin D is important for bone health in the general population but the value of
      vitamin D supplementation, and the role of 25-hydroxyvitamin D independently of
      1,25-dihydroxyvitmain D, in individuals with chronic kidney disease (CKD),
      particularly in those who require dialysis, remains uncertain. Supplementation
      may improve some biochemical parameters, such as reducing PTH levels in patients
      to CKD-stage 4 who have vitamin D deficiency; but it remains to be established
      whether the role of nutritional vitamin D in maintaining bone health in the
      general population can be extrapolated to the CKD population. There is currently
      insufficient evidence to recommend conclusively that nutritional vitamin D
      supplementation should be prescribed to individuals with CKD who have 25
      hydroxyvitamin D deficiency, either for skeletal or non-skeletal health outcomes.

PMID- 28429559
TI  - Chronic kidney disease mineral and bone disorders; controversies and directions.

PMID- 28429560
TI  - Is there a role for newer biomarkers in chronic kidney disease-mineral and bone
      disorder management?
AB  - The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD)
      relies largely on clinical judgement and assessment of biochemical parameters
      including serum calcium, phosphate and intact parathyroid hormone concentrations.
      In the past two decades, there has been a leap in the understanding of the
      pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The
      potential utility of these markers in this clinical setting is an area of intense
      investigation. In the absence of any guidelines aiding the clinician's
      understanding and application of these markers, we summarise the current
      available literature surrounding fibroblast growth factor-23, alpha-Klotho,
      sclerostin and serum calcification propensity testing and their respective assays
      in the context of CKD-MBD management.

PMID- 28429561
TI  - cfDNA screening performance: accounting for and reducing test failures.

PMID- 28429562
TI  - Predictors of the health-related quality of life of Chinese people with major
      neurocognitive disorders and their caregivers: The roles of self-esteem and
      caregiver's burden.
AB  - AIM: The present research study aimed to identify and compare the clinical and
      non-clinical factors that predict the self-reported and proxy-reported health
      related quality of life (HRQoL) of people with major neurocognitive disorder
      (PwND) who are living at home in a Chinese society. METHODS: A total of 57
      Chinese PwND-family caregiver dyads that were using the services of local senior
      centers were recruited through a cross-sectional survey with convenience
      sampling. Each PwND and caregiver rated the PwND's HRQoL independently by using
      the Quality of Life-Alzheimer's disease measure. Additional measures included the
      Rosenberg Self-Esteem Scale (RSES), Index for Managing Memory Loss, Geriatric
      Depression Scale, Cornell Scale for Depression in Dementia and Zarit Burden
      Inventory. RESULTS: The results of hierarchical multiple linear regression
      analyses showed that the PwND's self-rated HRQoL and caregiver-rated HRQoL were
      found to be predicted by different clinical and non-clinical variables. In
      particular, the self-esteem of PwND had the highest predictive power for the self
      rated HRQoL, whereas the caregiver burden is the only significant predictor for
      the caregiver-rated HRQoL. CONCLUSIONS: In the present study, the self-esteem of
      PwND and the caregiver's burden were found to be important factors predicting
      self-rated HRQoL and caregiver-rated HRQoL respectively, which is probably
      because of the influence of traditional Chinese cultural values. Thus, it is
      important for non-pharmacological interventions to address these special needs to
      promote HRQoL for this population. Geriatr Gerontol Int 2017; 17: 2319-2328.

PMID- 28429563
TI  - The second meeting of the Northeastern Evolutionary Primatologists.

PMID- 28429564
TI  - Small things and big news at the 2016 SAfA meetings in Toulouse, France.

PMID- 28429565
TI  - European Acheuleans. northern v. southern Europe: hominins, technical behaviour,
      chronological and environmental contexts. International Conference, National
      Museum of Natural History, Paris, France November 19-21, 2014.

PMID- 28429566
TI  - The extended reach of the selfish gene.

PMID- 28429568
TI  - The evolutionary radiation of plesiadapiforms.
AB  - Very shortly after the disappearance of the non-avian dinosaurs, the first
      mammals that had features similar to those of primates started appearing. These
      first primitive forms went on to spawn a rich diversity of plesiadapiforms, often
      referred to as archaic primates. Like many living primates, plesiadapiforms were
      small arboreal animals that generally ate fruit, insects, and, occasionally,
      leaves. However, this group lacked several diagnostic features of euprimates.
      They also had extraordinarily diverse specializations, represented in eleven
      families and more than 140 species, which, in some cases, were like nothing seen
      since in the primate order. Plesiadapiforms are known from all three Northern
      continents, with representatives that persisted until at least 37 million years
      ago. In this article we provide a summary of the incredible diversity of
      plesiadapiform morphology and adaptations, reviewing our knowledge of all eleven
      families. We also discuss the challenges that remain in our understanding of
      their ecology and evolution.

PMID- 28429569
TI  - Celebrating fifty years of research at the Duke Lemur Center.

PMID- 28429567
TI  - The Tsimane Health and Life History Project: Integrating anthropology and
      biomedicine.
AB  - The Tsimane Health and Life History Project, an integrated bio-behavioral study
      of the human life course, is designed to test competing hypotheses of human life
      history evolution. One aim is to understand the bidirectional connections between
      life history and social behavior in a high-fertility, kin-based context lacking
      amenities of modern urban life (e.g. sanitation, banks, electricity). Another aim
      is to understand how a high pathogen burden influences health and well-being
      during development and adulthood. A third aim addresses how modernization shapes
      human life histories and sociality. Here we outline the project's goals, history,
      and main findings since its inception in 2002. We reflect on the implications of
      current findings and highlight the need for more coordinated ethnographic and
      biomedical study of contemporary nonindustrial populations to address broad
      questions that can situate evolutionary anthropology in a key position within the
      social and life sciences.

PMID- 28429570
TI  - Why can we ask why?: Our adaptability adaptation programs us not to be
      programmed.

PMID- 28429572
TI  - Finding Chemical Structures Corresponding to a Set of Coordinates in Chemical
      Descriptor Space.
AB  - When chemical structures are searched based on descriptor values, or descriptors
      are interpreted based on values, it is important that corresponding chemical
      structures actually exist. In order to consider the existence of chemical
      structures located in a specific region in the chemical space, we propose to
      search them inside training data domains (TDDs), which are dense areas of a
      training dataset in the chemical space. We investigated TDDs' features using
      diverse and local datasets, assuming that GDB11 is the chemical universe. These
      two analyses showed that considering TDDs gives higher chance of finding chemical
      structures than a random search-based method, and that novel chemical structures
      actually exist inside TDDs. In addition to those findings, we tested the
      hypothesis that chemical structures were distributed on the limited areas of
      chemical space. This hypothesis was confirmed by the fact that distances among
      chemical structures in several descriptor spaces were much shorter than those
      among randomly generated coordinates in the training data range.

PMID- 28429571
TI  - Melatonin antagonizes interleukin-18-mediated inhibition on neural stem cell
      proliferation and differentiation.
AB  - Neural stem cells (NSCs) are self-renewing, pluripotent and undifferentiated
      cells which have the potential to differentiate into neurons, oligodendrocytes
      and astrocytes. NSC therapy for tissue regeneration, thus, gains popularity.
      However, the low survivals rate of the transplanted cell impedes its utilities.
      In this study, we tested whether melatonin, a potent antioxidant, could promote
      the NSC proliferation and neuronal differentiation, especially, in the presence
      of the pro-inflammatory cytokine interleukin-18 (IL-18). Our results showed that
      melatonin per se indeed exhibited beneficial effects on NSCs and IL-18 inhibited
      NSC proliferation, neurosphere formation and their differentiation into neurons.
      All inhibitory effects of IL-18 on NSCs were significantly reduced by melatonin
      treatment. Moreover, melatonin application increased the production of both brain
      derived and glial cell-derived neurotrophic factors (BDNF, GDNF) in IL-18
      stimulated NSCs. It was observed that inhibition of BDNF or GDNF hindered the
      protective effects of melatonin on NSCs. A potentially protective mechanism of
      melatonin on the inhibition of NSC's differentiation caused IL-18 may attribute
      to the up-regulation of these two major neurotrophic factors, BNDF and GNDF. The
      findings indicate that melatonin may play an important role promoting the
      survival of NSCs in neuroinflammatory diseases.

PMID- 28429573
TI  - Comment on 'A critical evaluation of the current "p-value controversy" '.

PMID- 28429574
TI  - Flip angle optimization for balanced SSFP: Cardiac cine imaging following the
      application of standard extracellular contrast agent (gadobutrol).
AB  - PURPOSE: To investigate the effect of the flip angle (FA) on the blood-myocardium
      contrast and to define the FA leading to highest image quality in contrast
      enhanced balanced steady-state free precession (bSSFP) images. bSSFP images
      provide excellent contrast between myocardium and blood with high signal-to-noise
      and contrast-to-noise ratios (SNR, CNR). In clinical practice, bSSFP images are
      typically acquired following the injection of extracellular contrast agents
      (ECAs), although ECAs decrease the blood-myocardium contrast. MATERIALS AND
      METHODS: First, a theoretical optimization was performed to determine the FA that
      maximizes CNR in bSSFP imaging 2-20 minutes after application of ECA. Second
      signal-ratios, contrast, SNR, and CNR were assessed in vivo in 25 patients in
      bSSFP images at 1.5T acquired before (FA = 50 degrees ) and 10-15 minutes after
      (FAs = 50 degrees , 80 degrees , 90 degrees , 100 degrees ) application of a
      double-dose contrast agent. Image quality was assessed by two readers. RESULTS:
      Simulations yielded FAs in the range of 85-100 degrees  for optimal CNR in
      contrast-enhanced images. In vivo comparison of conventionally acquired cine
      images (FA 50 degrees ) showed an increase in CNR between blood and myocardium by
      57% in diastole and 78% in systole in adapted contrast-enhanced bSSFP images (FA
      100 degrees ). Contrast-enhanced images with an FA of 100 degrees  were rated
      highest in image quality assessment. CONCLUSION: By means of FA adaptation a
      similar blood-myocardium contrast can be achieved in contrast-enhanced bSSFP as
      in unenhanced bSSFP imaging with an increase in CNR. LEVEL OF EVIDENCE: 1
      Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:255-261.

PMID- 28429575
TI  - Recovery from Talaromyces marneffei involving the kidney in a renal transplant
      recipient: A case report and literature review.
AB  - Talaromyces marneffei is an emerging opportunistic infection among
      immunocompromised patients. We observe the first native case of disseminated T.
      marneffei involving the kidney in a renal transplant recipient in mainland China.
      We describe the comprehensive clinical course, and ultrasound imaging of renal
      transplant biopsy, pathologic images, and electron microscopy observation of the
      biopsy specimen, highlighting the relevance of biopsy findings and the blood
      culture. We also focus on the treatment and good outcome of the patient. Then we
      review the literature and show the additional 10 reported cases of T. marneffei
      in renal transplant recipients. In addition, we discuss the new methods of rapid
      diagnosis of T. marneffei. In brief, timely diagnosis and proper treatment of T.
      marneffei infection is important in renal transplant recipients.

PMID- 28429576
TI  - Suppression of OsMADS7 in rice endosperm stabilizes amylose content under high
      temperature stress.
AB  - High temperature significantly alters the amylose content of rice, resulting in
      mature grains with poor eating quality. However, only few genes and/or
      quantitative trait loci involved in this process have been isolated and the
      molecular mechanisms of this effect remain unclear. Here, we describe a floral
      organ identity gene, OsMADS7, involved in stabilizing rice amylose content at
      high temperature. OsMADS7 is greatly induced by high temperature at the early
      filling stage. Constitutive suppression of OsMADS7 stabilizes amylose content
      under high temperature stress but results in low spikelet fertility. However,
      rice plants with both stable amylose content at high temperature and normal
      spikelet fertility can be obtained by specifically suppressing OsMADS7 in
      endosperm. GBSSI is the major enzyme responsible for amylose biosynthesis. A low
      filling rate and high expression of GBSSI were detected in OsMADS7 RNAi plants at
      high temperature, which may be correlated with stabilized amylose content in
      these transgenic seeds under high temperature. Thus, specific suppression of
      OsMADS7 in endosperm could improve the stability of rice amylose content at high
      temperature, and such transgenic materials may be a valuable genetic resource for
      breeding rice with elite thermal resilience.

PMID- 28429577
TI  - Investigating general medication prescription by general practitioners during a
      12-month randomized controlled weight loss trial.
AB  - Much healthcare expenditure is on pharmaceutical drugs. Expenditure on
      medications has increased both in absolute terms, and as a proportion of total
      health expenditure. No previous studies have investigated the prescribing costs
      by general practitioners when managing patients during a weight loss
      intervention. This study evaluated the medication costs by individual class
      during a 1-year study in which 268 participants were randomized to one of two
      weight loss programmes, either standard care (SC) as defined by national
      guidelines, or a commercial provider (Weight Watchers) (CP). The baseline body
      mass index of participants (mean +/- standard deviation) was 32.0 +/- 2.5 kg m-2
      , their body weight was 87.5 +/- 11.8 kg, and age 47.4 +/- 11.7 years. Weight
      loss for the SC and CP groups was -2.6 and -6.1 kg, respectively (between group
      difference; P < 0.0001). The greater weight loss in the CP group compared to SC
      was accompanied by larger reductions in waist circumference and fat mass. The CP
      group also had significantly greater improvements than SC in high-density
      lipoprotein cholesterol. Despite SC participants being prescribed and spending
      more on medications than the CP group with no better weight or metabolic
      outcomes, this was not of statistical significance. For both groups the highest
      proportion of prescriptions (>=30% of medications) was for control of risk
      factors for cardiovascular disease. In conclusion, this study indicates that
      obesity treatment via a shared care approach with a CP results in greater weight
      loss and some better clinical outcomes, but despite lower medication costs
      overall, this was not significant when compared to SC treatment.

PMID- 28429578
TI  - Soy isoflavones enhance beta-defensin synthesis and secretion in endometrial
      epithelial cells with exposure to TLR3 agonist polyinosinic-polycytidylic acid.
AB  - PROBLEM: beta-defensins are important innate chemical barriers that protect the
      endometrium from pathogen invasion. The effects of soy isoflavones, genistein and
      daidzein, on the expression and secretion of porcine beta-defensins (PBD) in
      endometrial epithelial cells were investigated under normal or poly I:C
      stimulated conditions. METHOD OF STUDY: Primary cultured porcine endometrial
      epithelial (PE) cells were pretreated with genistein or daidzein followed by poly
      I:C inoculation. During treatment, the culture media were analyzed for PBD 1-4
      secretion by ELISA and the total RNA for PBD gene expression by quantitative RT
      PCR. RESULTS: Porcine endometrial epithelial cells constitutively expressed PBD 1
      4 and secreted PBD-1, PBD-2, and PBD-4. Genistein and daidzein enhanced PBD-2
      expression and PBD-2 and PBD-3 secretion. These compounds also potentiated PBD-2
      and PBD-3 expression and secretion which were upregulated by poly I:C.
      CONCLUSION: Soy isoflavones, genistein and daidzein, could be potentially used
      for promoting the innate host defense of endometrium against infection.

PMID- 28429579
TI  - Contribution to the discussion of "A critical evaluation of the current 'p-value
      controversy'".

PMID- 28429580
TI  - Lanthanide Ions Coupled with Photoinduced Electron Transfer Generate Strong
      Reduction Potentials from Visible Light.
AB  - Metal ions can have beneficial effects on photoinduced electron transfer. Merging
      such metal-ion-coupled electron transfer (MCET) with consecutive photoinduced
      electron transfer (conPET) enables the one-electron reduction of chlorobenzene
      with blue light in the presence of diisopropylethylamine as an electron donor.
      The presence of the metal ions extends the substrate scope of the photoredox
      catalysis to extreme reduction potentials (beyond -3 V vs. SCE).

PMID- 28429582
TI  - Obesity and addiction: can a complication of surgery help us understand the
      connection?
AB  - Obesity is a multifactorial, chronic disease that has proven difficult to treat.
      An increased understanding of aetiological mechanisms is critical to the
      development of more effective obesity prevention and treatment strategies. A
      growing body of empirical evidence has demonstrated parallels between obesity,
      overeating and substance abuse, including shared behavioural, psychological and
      neurophysiological factors implicated in the excessive intake of both food and
      substances of abuse. Several different lines of research have recently emerged
      that hold the potential to shed light on the connection between obesity, food
      reward and addiction, with studies examining changes in alcohol use/misuse after
      weight loss surgery providing a particularly interesting perspective on these
      interrelationships. However, these lines of investigation have proceeded in
      relative isolation, and relevant research findings have yet to be integrated in a
      synthesized, comprehensive manner. To provide an opportunity to achieve such a
      synthesis, a scientific symposium was convened at the Radcliffe Institute in
      Cambridge, Massachusetts. Invited participants were researchers working in
      diverse domains related to the intersection between obesity and addiction.
      Extensive discussion was generated suggesting novel research directions. In this
      article, we summarize and synthesize the symposium participants' ongoing research
      in this area, incorporating additional relevant research holding potential clues
      regarding the connections between obesity, weight loss surgery and addiction.

PMID- 28429583
TI  - A qualitative study of the role of Australian general practitioners in the
      surgical management of obesity.
AB  - General practitioners (GPs) are increasingly managing patients with class 2 and 3
      obesity (body mass index [BMI] > 35 and 40 kg/m2 , respectively). Bariatric
      surgery is considered for patients with class 2 obesity and comorbidities or
      class 3 obesity where sustained weight loss using non-surgical interventions has
      not been achieved. In Australia, GPs facilitate access to surgery through
      referral processes, but the nature of GP involvement in bariatric pre- and post
      surgery care is currently unclear. This qualitative study involved 10 in-depth
      interviews with GPs and 20 interviews with adults who had all undergone
      laparoscopic adjustable gastric banding (LAGB) for weight management in Tasmania,
      Australia. Interviews were transcribed and analysed thematically. Referrals for
      bariatric surgery commonly occurred at the patient's request or to manage
      comorbidity. Consistent with previous studies, for GPs, referral patterns were
      influenced by previous case experience and patients' financial considerations.
      Accessibility of surgery was also a consideration. Post-surgery, there was a lack
      of clarity about the role of GPs, with patients generally preferring the surgical
      team to manage the LAGB. In bariatric surgery, patient preference for surgery,
      access and comorbidity are key drivers for referral and post-surgical monitoring
      and support. Greater role clarity and enhanced collaboration between surgeons,
      GPs and patients following surgery is likely to enhance the experience and
      outcomes for patients.

PMID- 28429581
TI  - Nighttime is the worst time: Parental fear of hypoglycemia in young children with
      type 1 diabetes.
AB  - BACKGROUND: Fear of hypoglycemia is common in parents of young children with type
      1 diabetes (T1D), but little is known about the specific fears that parents most
      often experience. Hypoglycemia fear has been associated with poorer glycemic
      control in older children, though not yet studied in a large cohort of very young
      children. MATERIALS AND METHODS: Parents of 549 children <7 years (mean 5.2 +/-
      1.2 years [19% <3 years]) with a mean diabetes duration of 2.4 +/- 1.0 years
      (range 1-6 years) and mean HbA1c 8.2% +/- 1.1% (66 +/- 12 mmol/mol) registered in
      the T1D Exchange completed the worry scale of the Hypoglycemia Fear Survey
      modified for parents (HFS-P). RESULTS: Mean parental fear of hypoglycemia worry
      score was 36.1 +/- 23.1 (possible range 0-100), with most frequent worries
      related to the child having a low while asleep and the child not recognizing a
      low. The mean worry score was not associated with the child's age, glycemic
      control, or recent severe hypoglycemic event. Parental worries about lows while
      sleeping were significantly higher in pump users than non-users (61% vs. 45%; P <
      .001), and tended to be higher in CGM users than non-users (62% vs 51%; P = .02).
      CONCLUSIONS: The greatest worries of parents of young children with T1D were
      related to hypoglycemia during sleep and other times/circumstances during which
      it would be difficult to detect hypoglycemia. Using advanced diabetes
      technologies may be an effort to temper fears about hypoglycemia during sleep,
      though the directionality of this relationship is undetermined. Additional
      studies can clarify this association and leverage use of diabetes technologies to
      improve glycemic control.

PMID- 28429584
TI  - DNA metabarcoding of unfractionated water samples relates phyto-, zoo- and
      bacterioplankton dynamics and reveals a single-taxon bacterial bloom.
AB  - Most studies of aquatic plankton focus on either macroscopic or microbial
      communities, and on either eukaryotes or prokaryotes. This separation is
      primarily for methodological reasons, but can overlook potential interactions
      among groups. Here we tested whether DNA metabarcoding of unfractionated water
      samples with universal primers could be used to qualitatively and quantitatively
      study the temporal dynamics of the total plankton community in a shallow
      temperate lake. Significant changes in the relative proportions of normalized
      sequence reads of eukaryotic and prokaryotic plankton communities over a 3-month
      period in spring were found. Patterns followed the same trend as plankton
      estimates measured using traditional microscopic methods. The bloom of a
      conditionally rare bacterial taxon belonging to Arcicella was characterized,
      which rapidly came to dominate the whole lake ecosystem and would have remained
      unnoticed without metabarcoding. The data demonstrate the potential of universal
      DNA metabarcoding applied to unfractionated samples for providing a more holistic
      view of plankton communities.

PMID- 28429585
TI  - Eliminate Yellow fever Epidemics (EYE): a global strategy, 2017-2026.

PMID- 28429586
TI  - Bubble-Mediated Ultrasensitive Multiplex Detection of Metal Ions in Three
      Dimensional DNA Nanostructure-Encoded Microchannels.
AB  - The development of rapid and sensitive point-of-test devices for on-site
      monitoring of heavy-metal contamination has great scientific and technological
      importance. However, developing fast, inexpensive, and sensitive microarray
      sensors to achieve such a goal remains challenging. In this work, we present a
      DNA-nanostructured microarray (DNM) with a tubular three-dimensional sensing
      surface and an ordered nanotopography. This microarray enables enhanced molecular
      interaction toward the rapid and sensitive multiplex detection of heavy-metal
      ions. In our design, the use of DNA tetrahedral-structured probes engineers the
      sensing interface with spatially resolved and density-tunable sensing spots that
      improve the microconfined molecular recognition. A bubble-mediated shuttle
      reaction was used inside the DNM-functionalized microchannel to improve the
      target-capturing efficiency. Using this novel DNM biosensor, the sensitive and
      selective detection of multiple heavy-metal ions (i.e., Hg2+, Ag+, and Pb2+) was
      achieved within 5 min, the detection limit was down to 10, 10, and 20 nM for
      Hg2+, Ag+, and Pb2+, respectively. The feasibility of our DNM sensor was further
      demonstrated by probing heavy-metal ions in real water samples with a direct
      optical readout. Beyond metal ions, this unique DNM sensor can easily be extended
      to in vitro bioassays and clinical diagnostics.

PMID- 28429587
TI  - Thermal Conductivity Enhancement of Coaxial Carbon@Boron Nitride Nanotube Arrays.
AB  - We demonstrate the thermal conductivity enhancement of the vertically aligned
      carbon nanotube (CNT) arrays (from ~15.5 to 29.5 W/mK, ~90% increase) by
      encapsulating outer boron nitride nanotube (BNNT, 0.97 nm-thick with ~3-4 walls).
      The heat transfer enhancement mechanism of the coaxial C@BNNT was further
      revealed by molecular dynamics simulations. Because of their highly coherent
      lattice structures, the outer BNNT serves as additional heat conducting path
      without impairing the thermal conductance of inner CNT. This work provides deep
      insights into tailoring the heat transfer of arbitrary CNT arrays and will enable
      their broader applications as thermal interface material.

PMID- 28429588
TI  - Electric-Field-Adjustable Time-Dependent Magnetoelectric Response in Martensitic
      FeRh Alloy.
AB  - Steady or dynamic magnetoelectric response, selectable and adjustable by only
      varying the amplitude of the applied electric field, is found in a multiferroic
      FeRh/PMN-PT device. In-operando time-dependent structural, ferroelectric, and
      magnetoelectric characterizations provide evidence that, as in magnetic shape
      memory martensitic alloys, the observed distinctive magnetoelectric responses are
      related to the time-dependent relative abundance of antiferromagnetic
      ferromagnetic phases in FeRh, unbalanced by voltage-controlled strain. This
      flexible magnetoelectric response can be exploited not only for energy-efficient
      memory operations but also in other applications, where multilevel and/or
      transient responses are required.

PMID- 28429590
TI  - Palladium-Catalyzed, N-(2-Aminophenyl)acetamide-Assisted Ortho-Arylation of
      Substituted Benzamides: Application to the Synthesis of Urolithins B, M6, and M7.
AB  - Pd-catalyzed, selective, monoarylation of ortho-C-H bonds of various benzamides
      with aryl/heteroaryl iodides has been realized using N-(2-aminophenyl)acetamide
      (APA) as a new bidentate directing group for the first time. The reaction was
      tolerant of a wide range of functional groups, and a variety of biaryl amide
      derivatives were successfully prepared in good to moderate yield. The utilization
      of N-(2-aminophenyl)acetamide as a novel directing group, Mn(OAc)2 as a co
      oxidant (silver free reaction conditions), and absolute ortho-monoaryl
      selectivity are notable features of this reaction. In addition, the obtained
      monoarylated products could be further transformed into the bioactive natural
      products and human microflora metabolites of dietary ellagic acid derivatives,
      urolithin B, urolithin M6, and urolithin M7.

PMID- 28429589
TI  - Inhibition of Zero Drift in Perovskite-Based Photodetector Devices via [6,6]
      Phenyl-C61-butyric Acid Methyl Ester Doping.
AB  - Zero drift can severely deteriorate the stability of the light-dark current
      ratio, detectivity, and responsivity of photodetectors. In this paper, the
      effects of a [6,6]-phenyl-C61-butyric acid methyl ester (PCBM)-doped perovskite
      based photodetector device on the inhibition of zero drift under dark state are
      discussed. Two kinds of photodetectors (Au/CH3NH3PbIxCl3-x/Au and
      Au/CH3NH3PbIxCl3-x:PCBM/Au) were prepared, and the materials and photodetector
      devices were measured by scanning electron microscopy, X-ray diffraction,
      photoluminescence, ultraviolet absorption spectra, and current-voltage and
      current-time measurements. It was found that similar merit parameters, including
      light-dark current ratio (~102), detectivity (~1011 Jones), and responsivity were
      obtained for these two kinds of photodetectors. However, the drift of
      Au/CH3NH3PbIxCl3-x:PCBM/Au devices is negligible, while a drift of ~0.2 V exists
      in Au/CH3NH3PbIxCl3-x/Au devices. A new model is proposed based on the hindering
      theory of ion (vacancy) migration, and it is believed that the dopant PCBM can
      hinder the ion (vacancy) migration of perovskite materials to suppress the
      phenomenon of zero drift in perovskite-based photodetectors.

PMID- 28429591
TI  - High-Performance Furan-Containing Conjugated Polymer for Environmentally Benign
      Solution Processing.
AB  - Developing semiconducting polymers that exhibit both strong charge transport
      capability via highly ordered structures and good processability in
      environmentally benign solvents remains a challenge. Given that furan-based
      materials have better solubility in various solvents than analogous thiophene
      based materials, we have synthesized and characterized furanyl
      diketopyrrolopyrrole polymer (PFDPPTT-Si) together with its thienyl
      diketopyrrolopyrrole-based analogue (PTDPPTT-Si) to understand subtle changes
      induced by the use of furan instead of thiophene units. PTDPPTT-Si films
      processed in common chlorinated solvent exhibit a higher hole mobility (3.57 cm2
      V-1 s-1) than PFDPPTT-Si films (2.40 cm2 V-1 s-1) under the same conditions; this
      greater hole mobility is a result of tightly aggregated pi-stacking structures in
      PTDPPTT-Si. By contrast, because of its enhanced solubility, PFDPPTT-Si using
      chlorine-free solution processing results in a device with higher mobility (as
      high as 1.87 cm2 V-1 s-1) compared to that of the corresponding device fabricated
      using PTDPPTT-Si. This mobility of 1.87 cm2 V-1 s-1 represents the highest
      performances among furan-containing polymers reported to the best of our
      knowledge for nonchlorinated solvents. Our study demonstrates an important step
      toward environmentally compatible electronics, and we expect the results of our
      study to reinvigorate the furan-containing semiconductors field.

PMID- 28429592
TI  - Peptide Retention Time Prediction in Hydrophilic Interaction Liquid
      Chromatography: Data Collection Methods and Features of Additive and Sequence
      Specific Models.
AB  - The development of a peptide retention prediction model for hydrophilic
      interaction liquid chromatography (XBridge Amide column) is described for a
      collection of ~40 000 tryptic peptides. Off-line 2D LC-MS/MS analysis (HILIC
      RPLC) of S. cerevisiae whole cell lysate has been used to acquire retention
      information for a HILIC separation. The large size of the optimization data set
      (more than 2 orders of magnitude compared to previous reports) permits the
      accurate assignment of hydrophilic retention coefficients of individual amino
      acids, establishing both the effects of amino acid position relative to peptide
      termini and the influence of peptide secondary structure in HILIC. The accuracy
      of a simple additive model with peptide length correction (R2 value of ~0.96) was
      found to be much higher compared to an algorithm of similar complexity applied to
      RPLC (~0.91). This indicates significantly smaller influence of peptide secondary
      structure and interactions with counterions in HILIC. Nevertheless, sequence
      specific features were found. Helical peptides that tend to retain stronger than
      predicted in RPLC exhibit negative prediction errors using an additive HILIC
      model. N-cap helix stabilizing motifs, which increase retention of amphipathic
      helical peptides in RP, reduce peptide retention in HILIC independently of
      peptide amphipathicity. Peptides carrying multiple Pro and Gly (residues with
      lowest helical propensity) retain stronger than predicted. We conclude that
      involvement of the peptide backbone's carbonyl and amide groups in hydrogen-bond
      stabilization of helical structures is a major factor, which determines sequence
      dependent behavior of peptides in HILIC. The incorporation of observed sequence
      dependent features into our Sequence-Specific Retention Calculator HILIC model
      resulted in 0.98 R2 value correlation, significantly exceeding the predictive
      performance of all RP and HILIC models developed for complex mixtures of tryptic
      peptides.

PMID- 28429593
TI  - Model Amphiphilic Block Copolymers with Tailored Molecular Weight and Composition
      in PDMS-Based Films to Limit Soft Biofouling.
AB  - A set of controlled surface composition films was produced utilizing amphiphilic
      block copolymers dispersed in a cross-linked poly(dimethylsiloxane) network.
      These block copolymers contained oligo(ethylene glycol) (PEGMA) and fluoroalkyl
      (AF6) side chains in selected ratios and molecular weights to control surface
      chemistry including antifouling and fouling-release performance. Such properties
      were assessed by carrying out assays using two algae, the green macroalga Ulva
      linza (favors attachment to polar surfaces) and the unicellular diatom Navicula
      incerta (favors attachment to nonpolar surfaces). All films performed well
      against U. linza and exhibited high removal of attached sporelings (young plants)
      under an applied shear stress, with the lower molecular weight block copolymers
      being the best performing in the set. The composition ratios from 50:50 to 60:40
      of the AF6/PEGMA side groups were shown to be more effective, with several films
      exhibiting spontaneous removal of the sporelings. The cells of N. incerta were
      also removed from several coating compositions. All films were characterized by
      surface techniques including captive bubble contact angle, atomic force
      microscopy, and near edge X-ray absorption fine structure spectroscopy to
      correlate surface chemistry and morphology with biological performance.

PMID- 28429594
TI  - Ruthenium(II)-Catalyzed ortho-C-H Chalcogenation of Benzoic Acids via Weak O
      Coordination: Synthesis of Chalcogenoxanthones.
AB  - A general protocol for direct chalcogenation of inert C-H bonds of
      (hetero)aromatic carboxylic acids is developed with a ruthenium(II) catalyst
      using readily available starting materials, offering densely substituted ortho
      chalcogenyl aromatic acids in high yields (up to 96%). The strategy avoids the
      installation of an external directing group, use of metallic oxidants, and
      features operational simplicity with ample substrate scope. Synthetic application
      en route to biologically important chalcogenoxanthones is also demonstrated. This
      work represents the first example of ruthenium(II)-catalyzed direct C-H
      chalcogenation of benzoic acids.

PMID- 28429595
TI  - Ultrasensitive Detection of MicroRNAs with Morpholino-Functionalized Nanochannel
      Biosensor.
AB  - Here, we demonstrate a phosphorodiamidate morpholino oligos (PMO)-functionalized
      nanochannel biosensor for label-free detection of microRNAs (miRNAs) with
      ultrasensitivity and high sequence specificity. PMO, as a capture probe, was
      covalently anchored on the nanochannel surface. Because of the neutral character
      and high sequence-specific affinity of PMO, hybridization efficiency between PMO
      and miRNAs was enhanced, thus largely decreasing background signals and highly
      improving the detection specificity and sensitivity. The miRNAs detection was
      realized through observing the change of surface charge density when PMO/miRNAs
      hybridization occurred. Not only could the developed biosensor specifically
      discriminate complementary miRNAs (Let-7b) from noncomplementary miRNAs (miR-21)
      and one-base mismatched miRNAs (Let-7c), but also it could detect target miRNAs
      in serum samples. In addition, this nanochannel-based biosensor attained a
      reliable limit of detection down to 1 fM in PBS and 10 fM in serum sample,
      respectively. It is expected that such a new method will benefit miRNA detection
      in clinical diagnosis.

PMID- 28429596
TI  - Perpendicular Magnetic Anisotropy Preserved by Orbital Oscillation in Strained
      Tetragonal Fe4N/BiFeO3 Bilayers.
AB  - Orbital performances are important for inducing and manipulating the
      perpendicular magnetic anisotropy (PMA) in spintronic devices. Herewith, the
      orbital-mediated PMA in highly spin-polarized Fe4N are investigated in strained
      tetragonal Fe4N/BiFeO3(001) heterostructures with the FeAFeB/Fe-O2 termination
      using the first-principles calculations. Different from the d2 = dxz + dyz + dz2
      favored PMA in previously reported Fe film, for all the Fe4N atomic layers at the
      biaxial strain of S, all d orbitals (i.e., d1 = dxy + dx2-y2 and d2) make
      contributions to the PMA at S = 0% and in-plane magnetic anisotropy (IMA) at S = 
      2 and 2%. Specifically, the d1-d2 orbital oscillation preserves (or favors) the
      PMA in 0% strained Fe4N, where the stronger MAE contribution alternates between
      d1 and d2 in adjacent Fe4N layers. However, at S = -2 and 2%, the whole Fe4N
      shows IMA with stable d1 and d2 contributions. Moreover, the PMA in the
      unstrained Fe4N can be transformed into the IMA by a strain of -2% with a high
      spin polarization, where Fe4N/BiFeO3 interfacial effects are crucial. The PMA
      preserved by the controllably orbital oscillation in highly spin-polarized Fe4N
      paves a way for developing novel spintronic devices.

PMID- 28429597
TI  - Is capsule colonoscopy the solution for incomplete conventional colonoscopy?
AB  - The era of colon capsule endoscopy (CCE) started in 2007. Few years later second
      generation CCE (CCE-2) (Medtronic, Minneapolis, USA) was launched, featuring an
      improved optical system allowing for nearly 360 degrees  coverage via two 172
      degrees  angle cameras, and adaptive frame rate function (ranging from 4 to 35
      images per second depending on capsule motion). At present the main clinical
      indications for CCE are: a) completion of incomplete colonoscopy; b) polyp
      detection; and c) investigation of inflammatory bowel disease (IBD).

PMID- 28429598
TI  - Preliminary Clinical Validation of a Differential Correction Method for Improving
      Measurement Accuracy in Noninvasive Measurement of Blood Glucose Using Near
      Infrared Spectroscopy.
AB  - One of the main challenges in the noninvasive sensing of blood glucose by near
      infrared (NIR) spectroscopy is the background variations from light source drift,
      sweating, and temperature change at the human-machine interface. In this paper, a
      differential correction method based on the spectra from the floating-reference
      position and measuring position is proposed to eliminate these spectral
      variations from background interferences. Its effectiveness was validated by in
      vitro and in vivo experiments in which the diffuse reflectance of intralipid
      solutions and human skin was collected at the source distances of 0.6 mm and 2 mm
      by the custom-built system with six super-luminescent emitting diodes (SLEDs)
      light source. The results showed that, for the in vitro experiments of intralipid
      solutions, the coefficients of variations of diffuse reflectance decreased by
      20.5% under all the six wavelengths after differential correction. For the in
      vivo experiments of oral glucose tolerance tests (OGTTs), partial least squares
      (PLS) regression models between glucose concentrations and the diffuse
      reflectance from palm skin were built, and the root mean square error of cross
      validation (RMSECV) decreased by 38.0% on average after the differential
      correction. Further, the spectra of the oral water tolerance tests (OWTTs) were
      collected for correlation with glucose concentration in OGTTs, and their
      correlation coefficients (R) decreased by 35.0% on average after the differential
      correction. Therefore, this differential correction method based on the spectra
      from the floating-reference position and measuring position can weaken the
      influence of background variations on the NIR spectroscopy and has promising
      potential in in vivo detection, especially for noninvasive blood glucose
      measurement.

PMID- 28429599
TI  - Lipoprotein-Associated Phospholipase A2 and Risk of Carotid Atherosclerosis and
      Cardiovascular Events in Community-Based Older Adults in China.
AB  - We explored the associations between lipoprotein-associated phospholipase A2 (Lp
      PLA2) level and carotid atherosclerosis with all phenotypes and cardiovascular
      disease (CVD) events in Chinese older adults. A total of 1257 adults aged >=55
      years who were free of CVD were enrolled in this cohort study. Lipoprotein
      associated phospholipase A2 level was evaluated in 3 categories: Lp-PLA2 < 175,
      175<= Lp-PLA2 < 223, and Lp-PLA2 >= 223 ng/mL. The highest level of Lp-PLA2 was
      independently associated with common carotid artery intima-media thickening
      (>=1.0 mm; odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.14-2.26) and
      carotid plaque (OR: 1.42, 95% CI: 1.01-1.99) in individuals without carotid
      artery stenosis. At the end of the 5-year follow-up, after adjustment for CVD
      risk factors and carotid atherosclerosis status, Lp-PLA2 had remained an
      independent predictor for myocardial infarction (MI; hazard ratio [HR]: 1.90, 95%
      CI: 1.02-3.55) and CVD death (HR: 1.78, 95% CI: 1.02-3.13). However, no
      association was found with stroke. Therefore, elevated Lp-PLA2 level in the older
      adults studied was associated with an increased risk of carotid atherosclerosis
      and MI and CVD mortality. Lipoprotein-associated phospholipase A2 assessment
      might be used for MI and CVD death risk prediction.

PMID- 28429600
TI  - Changes in mental health research over the 50 years of the ANZJP.

PMID- 28429601
TI  - Later-Life Preparation Patterns on Depression Among Korean Baby Boom Generations.
AB  - The aim of this study was to examine the later-life preparation pattern of Korean
      baby boomers and its effect on depression. Using the fourth wave of Korean
      Retirement and Income Study, later-life preparation was measured by economic,
      physical, and psychological preparation, and leisure, and family relationship
      satisfaction. The data analysis included latent class analysis, correlations,
      multiple logistic regression, and analysis of variance. Later-life patterns of
      Korean baby boomers were classified as high-level (35.7%), low-level (31.1%), and
      health and family relationship (33.2%) preparation patterns. For depression, the
      low-level pattern was associated with significantly higher level of depression;
      however, no differences were found in other two patterns. Researchers recommended
      a postretirement program to reflect the unique characteristics of Korean baby
      boomers. Moreover, findings regarding the importance of health and family
      relationships can be applied to other countries that have historical and cultural
      backgrounds similar to Korea.

PMID- 28429602
TI  - Endoscopic treatment of symptomatic fibroids at reproductive age and beyond.
AB  - OBJECTIVES: To evaluate the feasibility of endoscopic treatment of symptomatic
      uterine fibroids based on patient and fibroid characteristics in reproductive,
      pre-menopausal and post-menopausal women. MATERIAL AND METHODS: The medical
      records of women with symptomatic uterine fibroids who underwent surgical
      procedures from 2010 to 2015 were retrospectively reviewed. RESULTS: A total of
      819 patients, of which 710 (86.6%) underwent endoscopic procedures. The mean age
      of women who underwent laparoscopic myomectomy (LM) was 36.77 +/- 6.54 and
      hysteroscopic myomectomy (HSCM) was 43.10 +/- 10.26. The mean cumulative diameter
      of fibroids in the LM was 8.94 +/- 3.1 and 3.68 +/- 1.64 cm in the HSCM.
      Furthermore, LM and HCSM were performed when the mean diameter of the largest
      fibroid was up to 18.50 and 5.5 cm, respectively. The mean age of women in
      laparoscopic supracervical hysterectomy (LSH) was 46.02 +/- 6.13 and total
      laparoscopic hysterectomy (TLH) was 47.30 +/- 8.12. The mean cumulative diameter
      of fibroids in the LSH was greater than in the TLH, at 8.94 +/- 3.1 and 7.63 +/-
      3.60 cm, respectively. CONCLUSIONS: Uterus-preserving procedures are feasible,
      even if the largest fibroid diameter is more than 10 cm in LM and equal to 5.5 cm
      in HSCM. For pre- and post-menopausal women, TLH is the definitive treatment
      modality for uterine fibroids, and LSH represents an alternative to TLH.

PMID- 28429603
TI  - Effect of High-Flow Nasal Cannula Oxygen Therapy Versus Conventional Oxygen
      Therapy and Noninvasive Ventilation on Reintubation Rate in Adult Patients After
      Extubation: A Systematic Review and Meta-Analysis of Randomized Controlled
      Trials.
AB  - PURPOSE: We conducted a systematic review and meta-analysis of randomized
      controlled trials (RCTs) to evaluate the effect of high-flow nasal cannula (HFNC)
      on reintubation in adult patients. PROCEDURES: Ovid Medline, Embase, and Cochrane
      Database of Systematic Reviews were searched up to November 1, 2016, for RCTs
      comparing HFNC versus conventional oxygen therapy (COT) or noninvasive
      ventilation (NIV) in adult patients after extubation. The primary outcome was
      reintubation rate, and the secondary outcomes included complications, tolerance
      and comfort, time to reintubation, length of stay, and mortality. Dichotomous
      outcomes were presented as risk ratio (RR) with 95% confidence intervals (CIs)
      and continuous outcomes as weighted mean difference and 95% CIs. The random
      effects model was used for data pooling. FINDINGS: Seven RCTs involving 2781
      patients were included in the analysis. The HFNC had a similar reintubation rate
      compared to either COT (RR, 0.58; 95% CI, 0.21-1.60; P = .29; 5 RCTs, n = 1347)
      or NIV (RR, 1.11; 95% CI, 0.88-1.40; P = .37; 2 RCTs, n = 1434). In subgroup of
      critically ill patients, the HFNC group had a significantly lower reintubation
      rate compared to the COT group (RR, 0.35; 95% CI, 0.19-0.64; P = .0007; 2 RCTs, n
      = 632; interaction P = .07 compared to postoperative subgroup). Qualitative
      analysis suggested that HFNC might be associated with less complications and
      improved patient's tolerance and comfort. The HFNC might not delay reintubation.
      Trial sequential analysis on the primary outcome showed that required information
      size was not reached. CONCLUSION: The evidence suggests that COT may still be the
      first-line therapy in postoperative patients without acute respiratory failure.
      However, in critically ill patients, HFNC may be a potential alternative
      respiratory support to COT and NIV, with the latter often associating with
      patient intolerance and requiring a monitored setting. Because required
      information size was not reached, further high-quality studies are required to
      confirm these results.

PMID- 28429605
TI  - Parent perspectives on home participation of high-functioning children with
      autism spectrum disorder compared with a matched group of children without autism
      spectrum disorder.
AB  - Few studies have focused on home participation of high-functioning children with
      autism spectrum disorder. We employed a mixed-methods design to explore and
      compare parent perspectives on (1) participation of children with and without
      autism spectrum disorder in activities at home, (2) the environmental features
      and resources that affect these children's home participation and (3) the
      strategies parents use to help their children participate at home. The
      Participation and Environment Measure for Children and Youth (PEM-CY) was used to
      gather online survey and qualitative data from parents of 99 high-functioning
      children with autism spectrum disorder and 241 children without autism spectrum
      disorder. Independent sample t-tests and chi2 tests were used to explore
      differences between groups, and Cohen's d was calculated to examine effect sizes.
      Differences were obtained on all Participation and Environment Measure for
      Children and Youth dimensions but particularly when comparing parents'
      satisfaction and perceived environmental barriers to their children's
      participation. The qualitative analyses revealed that parents in both groups used
      similar strategies to facilitate their children's participation at home, although
      parents of children with autism spectrum disorder made use of more distinct
      modifications. Our results highlight the importance of environmental aspects and
      point to how practitioners can support families in their efforts to promote their
      child's participation at home.

PMID- 28429604
TI  - Intra-arterial verapamil post-thrombectomy is feasible, safe, and neuroprotective
      in stroke.
AB  - Large vessel ischemic stroke represents the most disabling subtype. While t-PA
      and endovascular thrombectomy can recanalize the occluded vessel, good clinical
      outcomes are not uniformly achieved. We propose that supplementing endovascular
      thrombectomy with superselective intra-arterial (IA) verapamil immediately
      following recanalization could be safe and effective. Verapamil, a calcium
      channel blocker, has been shown to be an effective IA adjunct in a pre-clinical
      mouse focal ischemia model. To demonstrate translational efficacy, mechanism,
      feasibility, and safety, we conducted a group of translational experiments. We
      performed in vivo IA dose-response evaluation in our animal stroke model with
      C57/Bl6 mice. We evaluated neuroprotective mechanism through in vitro primary
      cortical neuron (PCN) cultures. Finally, we performed a Phase I trial, SAVER-I,
      to evaluate feasibility and safety of administration in the human condition. IA
      verapamil has a likely plateau or inverted-U dose-response with a defined
      toxicity level in mice (LD50 16-17.5 mg/kg). Verapamil significantly prevented
      PCN death and deleterious ischemic effects. Finally, the SAVER-I clinical trial
      showed no evidence that IA verapamil increased the risk of intracranial
      hemorrhage or other adverse effect/procedural complication in human subjects. We
      conclude that superselective IA verapamil administration immediately following
      thrombectomy is safe and feasible, and has direct, dose-response-related benefits
      in ischemia.

PMID- 28429606
TI  - Parent and Patient Perceptions of Functional Impairment Due to Tourette Syndrome:
      Development of a Shortened Version of the Child Tourette Syndrome Impairment
      Scale.
AB  - The Child Tourette Syndrome Impairment Scale (CTIM) rates 37 problems in school,
      social, and home domains separately for tics and for comorbid diagnoses. However,
      a shorter version would be easier to implement in busy clinics. Using published
      data from 85 children with Tourette syndrome, 92 controls, and parents, factor
      analysis was used to generate a "mini-CTIM" composed of 12 items applied to tic
      and comorbid diagnoses. Child- and parent-rated mini-CTIM scores were compared
      and correlated across raters and accounting for clinician-rated tic severity and
      presence of attention-deficit hyperactivity disorder (ADHD) and obsessive
      compulsive disorder (OCD). The mini-CTIM achieved domain Cronbach alphas ranging
      from 0.71 to 0.94 and intra-item correlation coefficients ranging from 0.84 to
      0.96. The resulting scale correlated with clinician-rated tic severity and
      reflected the presence of ADHD and OCD. The mini-CTIM appears promising as a
      practical assessment tool for tic- and non-tic-related impairment in children
      with Tourette syndrome.

PMID- 28429607
TI  - Thalamic Hemorrhagic Stroke in the Term Newborn: A Specific Neonatal Syndrome
      With Non-uniform Outcome.
AB  - BACKGROUND: Neonatal thalamic hemorrhagic stroke is related to cerebral sinus
      venous thrombosis and associated with neurological sequelae. Predicting factors
      are however lacking. METHODS: Clinical and radiological findings at onset and on
      follow-up of 5 neonates with thalamic hemorrhage stroke are described. RESULTS:
      All neonates presented with abrupt lethargy, ophistotonos, irritability and/or
      seizures. The thalamic hemorrhagic stroke was most often unilateral (4/5),
      involving the posterior/entire thalamus in 3 cases and the anterior thalamus in
      2. Cerebral venous thrombosis was identified in a single patient. At follow-up,
      children with unilateral anterior thalamic hemorrhagic stroke demonstrated
      thalamic atrophy without neurological symptoms, whereas children whose thalamus
      lesion was extensive exhibit a porencephalic cavity and presented with late-onset
      epilepsy. DISCUSSION: Although deep cerebral venous thrombosis is probably the
      cause of neonatal thalamic hemorrhagic stroke, its radiological evidence is
      challenging. Outcome seems dependent of the size and location of thalamic
      hemorrhagic stroke. Epilepsy is a frequent morbidity after thalamic hemorrhagic
      stroke.

PMID- 28429608
TI  - Two times of trigeminal neuralgia resolution following hydrocephalus treatment in
      a patient with a high-voltage electric shock to his head: a case report and a
      review of the literature.
AB  - Hydrocephalus has rarely been reported to be associated with trigeminal
      neuralgia. Here we report for the first time a case of trigeminal neuralgia
      associated with hydrocephalus, whose symptoms completely resolved twice after
      ventriculoperitoneal shunting. The patient had a high-voltage electric shock to
      his head, which has not been reported in a patient with ventriculoperitoneal
      shunt to the best of our knowledge. The possible underlying mechanism of this
      situation is discussed in addition to a brief review of the literature.

PMID- 28429609
TI  - Chemical evaluation of the Rhynchophorus ferrugineus larvae fed on different
      substrates as human food source.
AB  - We investigated the chemical composition of the weevil Rhynchophorus ferrugineus
      larvae, traditionally used as human food in Asia and known worldwide as one of
      the most significant pest for palm trees. Total fat content and fatty acid
      composition were analyzed using standard methodologies in (1) weevil larvae
      reared on apple fruit slices and wild specimens collected from attacked (2)
      Phoenix canariensis and (3) Syagrus romanzoffiana palm trees. Total fat content
      was extremely high in all the specimens (ranged between 57.62 and 60.03% based on
      dry weight). Despite sharing the same prevalent fatty acids (myristic acid,
      palmitic acid, stearic acid, palmitoleic acid, oleic acid, alpha-linoleic acid,
      and alpha-linolenic acid), fatty acid composition of the wild weevil larvae
      significantly differed from that of the specimens raised on apple fruit, due to
      the presence of other minor compounds. In general, a good balance between
      unsaturated fatty acids (~53.68% of total fatty acids) and saturated fatty acids
      (~43.41% of total fatty acids) and a low cholesterol content (74.61-152.32 mg/kg
      based on dry matter) were detected in all the specimens. Conversely, the weevil
      larvae did not represent a good source of alpha-tocopherol (14.17-26.22 mg/kg
      based on dry matter). The ability of the protein extracts obtained from the
      weevil larvae to inhibit in vitro the angiotensin-converting enzyme, the main
      enzyme involved in blood pressure regulation, was also investigated. To simulate
      gastrointestinal digestion process, protein extracts were hydrolyzed by the
      gastrointestinal enzymes. A significantly lower IC50 (0.588-0.623 mg/ml) was
      measured in all the protein extracts after enzymatic hydrolysis versus the
      corresponding crude protein extracts (3.270-3.752 mg/ml). Given that the weevil
      larvae are able to provide interesting benefits for human health, this study
      supports their use as human food not just in the native countries where they are
      traditionally consumed and farmed but also throughout the world.

PMID- 28429610
TI  - Tomentodione E, a new sec-pentyl syncarpic acid-based meroterpenoid from the
      leaves of Rhodomyrtus tomentosa.
AB  - A new meroterpenoid, tomentodione E (1), along with four known ones (2-5) were
      isolated from the leaves of Rhodomyrtus tomentosa. Their structures were
      elucidated based on extensive spectroscopic data as well as computational
      methods. Compound 1 represents the first example of meroterpenoid possessing a
      sec-pentyl syncarpic acid motif coupled with a caryophyllene. Compounds 1-4 were
      evaluated for their in vitro antiviral activity against respiratory syncytial
      virus (RSV) with cytopathic effect (CPE) reduction assay, and 2 showed potent in
      vitro anti-RSV effect.

PMID- 28429611
TI  - Consensus Statement on Inpatient Use of Continuous Glucose Monitoring.
AB  - In June 2016, Diabetes Technology Society convened a panel of US experts in
      inpatient diabetes management to discuss the current and potential role of
      continuous glucose monitoring (CGM) in the hospital. This discussion combined
      with a literature review was a follow-up to a meeting, which took place in May
      2015. The panel reviewed evidence on use of CGM in 3 potential inpatient
      scenarios: (1) the intensive care unit (ICU), (2) non-ICU, and (3) transitioning
      outpatient CGM use into the hospital setting. Panel members agreed that data from
      limited studies and theoretical considerations suggested that use of CGM in the
      hospital had the potential to improve patient clinical outcomes, and in
      particular reduction of hypoglycemia. Panel members discussed barriers to
      widespread adoption of CGM, which patients would benefit most from use of this
      technology, and what type of outcome studies are needed to guide use of CGM in
      the inpatient setting.

PMID- 28429612
TI  - A unique database for gathering data from a mobile app and medical prescription
      software: a useful data source to collect and analyse patient-reported outcomes
      of depression and anxiety symptoms.
AB  - A unique database named 'AN-SAPO' was developed by Iwato Corp. and Japan Brain
      Corp. in collaboration with the psychiatric clinics run by Himorogi Group in
      Japan. The AN-SAPO database includes patients' depression/anxiety score data from
      a mobile app named AN-SAPO and medical records from medical prescription software
      named 'ORCA'. On the mobile app, depression/anxiety severity can be evaluated by
      answering 20 brief questions and the scores are transferred to the AN-SAPO
      database together with the patients' medical records on ORCA. Currently, this
      database is used at the Himorogi Group's psychiatric clinics and has over 2000
      patients' records accumulated since November 2013. Since the database covers
      patients' demographic data, prescribed drugs, and the efficacy and safety
      information, it could be a useful supporting tool for decision-making in clinical
      practice. We expect it to be utilised in wider areas of medical fields and for
      future pharmacovigilance and pharmacoepidemiological studies.

PMID- 28429613
TI  - Effect of dietary supplementation with carnosic acid or vitamin E on animal
      performance, haematological and immunological characteristics of artificially
      reared suckling lambs before and after road transport.
AB  - To elucidate the influence of dietary carnosic acid (CA) and vitamin E on animal
      performance, immune response indicators and haematological parameters before and
      after transport stress, 24 lambs were individually fed ad libitum with milk
      replacer (MR) using an auto-feeder. Once daily the lambs received MR alone (Group
      CON, n = 8), MR + 0.096 g CA/kg live weight (LW) (Group CARN, n = 8) or MR +
      0.024 g of alpha-tocopheryl acetate per kg LW (Group VitE, n = 8). After reaching
      the target slaughter weight (12 +/- 0.5 kg), blood samples were collected to
      measure haematological and immunological parameters. Then, lambs were subjected
      to 4-h road transport and blood samples were collected again for haematological
      assessment. The animals were subsequently slaughtered. Before road transport,
      dietary CA supplementation promoted a descent of circulating white blood cells
      (WBC), red blood cells (RBC), haematocrit and haemoglobin concentration when
      compared with Groups CON and VitE (p < 0.05), but it did not affect production of
      cytokines by blood mononuclear cells. Road transport did not affect either RBC or
      haematocrit significantly. Nevertheless, transport affected leucocyte profile
      similarly in all the treatments, increasing granulocytes and monocytes
      proportions and decreasing lymphocytes. In contrast, after transport, WBC was
      increased in Group CARN, reaching similar values than Groups CON and VitE.
      However, under conditions of the present study, those modifications did not
      influence animal performance or immunity parameters of artificially reared
      suckling lambs.

PMID- 28429614
TI  - Are mothers' protective attachment strategies related to their children's
      strategies?
AB  - AIMS: We explored the relation between mothers' protective attachment strategies
      and those of their school-age children. METHODS: In total, 49 child-mother dyads
      participated in a short longitudinal study when the children were 5.5 and 6.0
      years old. Their strategies were first assessed with the Preschool Assessment of
      Attachment (PAA) and then with the School-age Assessment of Attachment (SAA).
      Mothers were assessed with the Adult Attachment Interview (AAI). The Dynamic
      Maturational Model of Attachment and Adaptation (DMM) was used to classify the
      assessments. RESULTS: The validity and precision of the DMM-AAI were supported:
      Mothers' AAI classifications were related to their referral group (normative or
      clinical) and measures of stress and distress. The DMM categories were more
      associated with risk than the Ainsworth categories. Types A, C and A/C were
      differentiated by trauma, triangulation and depression. Mothers' and children's
      protective attachment strategies were related, with B mothers having B children
      and A or C mothers having children using the same or opposite strategy. Children
      whose classification changed from the PAA to the SAA had mothers with complex
      traumas. CONCLUSION: When psychosocial treatment is needed, knowing whether
      mother and child use the same or different strategies and whether mothers have
      complex trauma can affect treatment success.

PMID- 28429615
TI  - Regulation of vascular large-conductance calcium-activated potassium channels by
      Nrf2 signalling.
AB  - BK channels are major ionic determinants of vasodilation. BK channel function is
      impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK
      beta1) subunits in response to increased oxidative stress. The nuclear factor E2
      related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of
      cellular redox status, and we hypothesized that it plays a central role in
      regulating BK channel function in diabetic vessels. We found that Nrf2 expression
      was markedly reduced in db/db diabetic mouse aortas, and this was associated with
      significant downregulation of BK-beta1. In addition, the muscle ring finger
      protein 1 (MuRF1), a known E-3 ligase targeting BK-beta1 ubiquitination and
      proteasomal degradation, was significantly augmented. These findings were
      reproduced by knockdown of Nrf2 by siRNA in cultured human coronary artery smooth
      muscle cells. In contrast, adenoviral transfer of Nrf2 gene in these cells
      downregulated MuRF1 and upregulated BK-beta1 expression. Activation of Nrf2 by
      dimethyl fumarate preserved BK-beta1 expression and protected BK channel and
      vascular function in db/db coronary arteries. These results indicate that
      expression of BK-beta1 is closely regulated by Nrf2 and vascular BK channel
      function can be restored by Nrf2 activation. Nrf2 should be considered a novel
      therapeutic target in the treatment of diabetic vasculopathy.

PMID- 28429616
TI  - Advanced surgical technique for invasive fungal sinusitis: endoscopic orbit-sinus
      combined approach.
AB  - BACKGROUND: Invasive fungal sinusitis is usually associated with poor prognosis,
      but no clear guidelines have been established for surgical treatment. Here, we
      report the development and application of the endoscopic orbit-sinus combined
      approach (EOSCA), a novel surgical technique to approach the nasal cavity and
      orbit concurrently, in patients with invasive fungal sinusitis with orbital
      infiltration. MATERIAL AND METHODS: Two patients with invasive fungal sinusitis
      infiltrating the orbit underwent EOSCA. Transnasal endoscopy was performed for
      maximum debulking of tissues infiltrated by fungi in the nasal cavity and orbit,
      before making an incision into the palpebral conjunctiva. An endoscope was then
      inserted into the orbit through the incision in the palpebral conjunctiva to
      remove adipose tissue and muscles that had been infiltrated by fungi from the
      orbital regions where the transnasal approach was difficult or impossible.
      Another surgeon assisted the procedure by operating an endoscope concurrently via
      the nasal cavity (four-hands technique). RESULTS: We were able to remove lesions
      safely and with precision, preserving visual acuity and a functional eyeball in
      both cases. Currently, the patients are alive, with no postoperative
      complications, recurrence, or disfigurement. CONCLUSIONS: This novel method shows
      promise as a safe and reliable surgical procedure for patients with invasive
      fungal sinusitis infiltrating into the orbit, with no postoperative
      complications, recurrence, or disfigurement.

PMID- 28429617
TI  - ESAS and FACT-B in eribulin-treated metastatic breast cancer patients: a
      multicenter, prospective and observational study.
AB  - AIM: Quality of life (QoL) is a critical issue for women with metastatic breast
      cancer (MBC). Eribulin mesylate represents a novel and active drug for pretreated
      MBC. Regretfully, few data exploring health-related (HR) QoL are available in
      unselected populations. PATIENTS & METHODS: A multicenter prospective
      observational study was conducted in 50 MBC patients treated with eribulin
      mesylate, in order to evaluate HRQoL and patients' well-being by using the
      Edmonton symptoms assessment scale (ESAS) and Functional Assessment of Cancer
      Therapy-Breast questionnaires. RESULTS: A significant ESAS score improvement was
      observed with a 10% median decrease. No differences were revealed for the QoL
      scores. CONCLUSION: The analysis of ESAS and Functional Assessment of Cancer
      Therapy scores showed that eribulin mesylate contributes to preserve QoL in MBC
      patients.

PMID- 28429618
TI  - The clinician perspective on sex differences in autism spectrum disorders.
AB  - Research studies using existing samples of individuals with autism spectrum
      disorders have identified differences in symptoms between males and females.
      Differences are typically reported in school age and adolescence, with
      similarities in symptom presentation at earlier ages. However, existing studies
      on sex differences are significantly limited, making it challenging to discern
      if, how, and at what point in development females with autism spectrum disorder
      actually exhibit a different behavioral presentation than males. The purpose of
      this study was to gather impressions from a large group of clinicians to isolate
      specific areas for future study of sex differences. Clinicians were surveyed
      about their opinions and perceptions of symptom severity in females, as compared
      to males, at different points during development. They were also asked to provide
      open-ended responses about female symptom presentation. Consistent with previous
      literature, clinicians noted more sex-related differences in restricted and
      repetitive behaviors and fewer differences for social communication features.
      Differences were most commonly observed in school age and adolescence, suggesting
      this time period as a critical and particularly vulnerable window for females
      with autism spectrum disorder. The results are discussed in the context of other
      male/female differences across development so that more targeted investigations
      of autism spectrum disorder sex differences across development.

PMID- 28429619
TI  - Addressing Parental Health in Pediatrics: Physician Perceptions of Relevance and
      Responsibility.
AB  - Pediatric guidelines recommend that providers address a range of parental health
      issues; however, adherence to these guidelines has been suboptimal. Drawing on a
      nationally-representative sample of children's primary care physicians, we
      examined whether providers view parental issues as relevant to child health and
      whether they believe it is their personal responsibility to address them. Issues
      included maternal depression, tobacco use, intimate partner violence, Tdap
      (tetanus, diphtheria, and acellular pertussis) immunization, family planning, and
      health insurance. While the majority of respondents endorsed the relevance of
      these issues to child health, particularly for issues with an established
      evidencebase, significantly fewer felt responsible for addressing them.
      Physicians who endorsed relevance or responsibility were almost always more
      likely to address these issues in their clinical practice. To advance parental
      health promotion practices, highlighting relevance to pediatric outcomes is an
      important first step, particularly for novel areas, while understanding what
      factors influence personal responsibility is necessary for all issues.

PMID- 28429620
TI  - Physician Perspectives on Decision Making for Treatment of Pediatric Sleep
      Disordered Breathing.
AB  - Sleep-disordered breathing (SDB) is prevalent in children and most commonly
      treated by surgery with adenotonsillectomy. We aimed to learn physician
      perspectives of social and communication factors that influence decision making
      for treatment of pediatric SDB. Purposive sampling identified 10 physician key
      informants across disciplines and practice settings, who participated in
      semistructured interviews regarding SDB care experiences and communication with
      parents. Interviews were analyzed using directed qualitative content analysis.
      Physicians provided a variety of perspectives on decision making for treatment
      that fell into 3 overarching themes: approach to surgery and alternatives,
      communication and decision making with families, and sociocultural
      factors/barriers to care. Perspectives were moderately heterogeneous, suggesting
      that individual social and relational elements may significantly influence how
      physicians refer patients and recommend treatment, and how parents choose surgery
      for this prevalent condition. These findings will inform development of
      culturally competent communication strategies and support tools to enhance shared
      decision making for physicians treating children with SDB.

PMID- 28429621
TI  - The Distribution and Movement of American Cockroaches in Urban Niches of New
      Orleans.
AB  - American cockroaches are an important source of household allergens in tropical
      and semitropical climates. To determine which outdoor niches produce American
      cockroaches, traps were placed at 40 homes in New Orleans to collect nymphs.
      Nymphs were collected from the sewers, yards, and within the homes themselves. To
      compare sewers and yards as sources of cockroaches entering homes, adult
      cockroaches were collected, marked, and released into yards and sewers. No sewer
      released cockroaches were collected in homes. Cockroaches released into yards
      were collected in the homes, suggesting that yards, rather than sewers, are a
      more important source niche. A field trial applying boric acid granules to the
      yard was performed in an effort to reduce entry of cockroaches. There was a
      significant reduction in the cockroach antigen collected in intervention homes
      compared with controls.

PMID- 28429622
TI  - Pharmacoepigenomic responses of antipsychotic drugs on pharmacogenes are likely
      to be modulated by miRNAs.
AB  - AIM: It is imperative to differentiate the role of host epigenetics from
      pharmacoepigenetics in resolving therapeutic response. Therefore, the objective
      was to identify how antipsychotic drugs influence epigenetic response on
      pharmacogenes. MATERIALS & METHODS: The study design was based on in vitro
      evaluation of pharmacoepigenetic response of haloperidol, clozapine and
      olanzapine. Post antipsychotic treatment, the alterations in expression of ABCB1,
      CYP1A2 and CYP3A4 were monitored, and followed up by promoter methylation and
      their target miRNA expression studies. Critical observations were followed up in
      a restrictive clinical setting. RESULTS: Under in vitro conditions increased
      expression of ABCB1, CYP1A2 and CYP3A4 was observed which seems to be regulated
      by miR-27a and miR-128a and not by methylation. A similar pattern was observed in
      clinical setting with ABCB1, which was reflective of good therapeutic response.
      CONCLUSION: The study demonstrates that antipsychotic drugs can influence miRNA
      mediated epigenetic response in pharmacogenes resulting in modulating therapeutic
      response.

PMID- 28429623
TI  - Schema therapy for personality disorders in older adults: a multiple-baseline
      study.
AB  - OBJECTIVE: No studies have been conducted yet into the effectiveness of treatment
      of personality disorders in later life. This study is a first test of the
      effectiveness of schema therapy for personality disorders in older adults.
      METHOD: Multiple-baseline design with eight cluster C personality disorder
      patients, with a mean age of   69. After a baseline phase with random length,
      schema therapy was given during the first year, followed by follow-up sessions
      during six months. Participants weekly rated the credibility of dysfunctional
      core beliefs. Symptomatic distress, early maladaptive schemas, quality of life
      and target complaints were assessed every six months and personality disorder
      diagnosis was assessed before baseline and after follow-up. Data were analyzed
      with mixed regression analyses. RESULTS: Results revealed significant linear
      trends during treatment phases, but not during baseline and follow-up. The scores
      during follow-up remained stable and were significantly lower compared to
      baseline, with high effect sizes. Seven participants remitted from their
      personality disorder diagnosis. CONCLUSION: Schema therapy appears an effective
      treatment for cluster C personality disorders in older adults. This finding is
      highly innovative as this is the first study exploring the effectiveness of
      psychotherapy, in this case schema therapy, for personality disorders in older
      adults.

PMID- 28429624
TI  - Impact of high-dose oleuropein on cisplatin-induced oxidative stress,
      genotoxicity and pathological changes in rat stomach and lung.
AB  - The current systemic treatments of the various solid tumors involve Cisplatin
      (CIS)-based chemotherapy. Due to its cytotoxicity, this approach is limited.
      Moreover, the safety of CIS is only discussed especially in breast and stomach
      cancers. Therefore, we, for the first time, explored the restorative efficacy of
      oleuropein (OLE), in stomach and lung injuries induced by CIS. Sprague-Dawley
      rats were divided into eight groups: control CIS, OLE and CIS + OLE. Single dose
      of (7 mg/kg) CIS was administered intraperitoneally to CIS and CIS + OLE groups.
      After 24 h, 50, 100 and 200 mg/kg OLE was given for three consecutive days to OLE
      and CIS + OLE groups. The 8-OH-dG, total oxidative/antioxidant status (TOS/TAS)
      and malondialdehyde (MDA) levels were evaluated and histopathological analyses
      were performed on the studied tissues. The results indicated that CIS
      significantly increased 8-OH-dG, MDA and TOS levels and caused severe tissue
      damages. However, high dose of OLE induced a significant decrease in the 8-OH-dG,
      MDA levels, an increase in TAS levels and it restores CIS-induced tissue damages.
      We hope that the results of this study will provide an impetus for future studies
      on novel therapeutic strategies including the protective use of oleuropein in
      gastric and lung cancers due to chemotherapy.

PMID- 28429625
TI  - Trichotillomania and its clinical relationship to depression and anxiety.
AB  - OBJECTIVE: Trichotillomania (TTM) is associated with high rates of co-occurring
      depression and anxiety disorders. What the co-occurrence of TTM, depression or
      anxiety disorders means clinically and cognitively, however, has garnered little
      research attention. METHODS: About 530 adults with TTM were examined on a variety
      of clinical measures including symptom severity, psychosocial measures of
      functioning, psychiatric comorbidity and neurocognitive testing assessing motor
      inhibition and cognitive flexibility. Clinical features and cognitive functioning
      were compared between TTM patients with current comorbid major depressive
      disorder (MDD), a current anxiety disorder, both MDD and an anxiety disorder, or
      neither. RESULTS: Of 530 participants, 58 (10.3%) had MDD only, 97 (18.3%) had an
      anxiety disorder only, 58 (10.3%) had both MDD and an anxiety disorder, and 317
      (59.8%) had neither. For almost all clinical measures, those with MDD only
      reported worse symptoms than those with an anxiety disorder only, and the
      combination of MDD and an anxiety disorder reported the worst level of symptom
      severity. CONCLUSIONS: These results suggest that adults with TTM and co
      occurring MDD and anxiety disorders exhibit unique clinical differences. The
      clinical differences may also have treatment implications.

PMID- 28429626
TI  - Promising immunotherapy against fungal diseases.
AB  - INTRODUCTION: Despite the relatively high efficacy of antifungal drugs, invasive
      fungal infections (IFIs) are still associated with tremendous morbidity and
      mortality, since late diagnosis makes an antifungal drug therapy inefficient.
      Therefore, antifungal immunotherapies to specifically strengthen the host's own
      immune mechanisms constitute an additional promising strategy in taking action
      against fungal pathogens. Areas covered: The authors summarize efforts in
      research and clinical trials to provide safe and efficient immunotherapeutic
      options against invasive fungal diseases. Treatment of IFIs is challenging as the
      number of available antifungals is limited and further complications include:
      toxicity, drug interactions and the emergence of drug resistance. Susceptibility
      is determined by the impaired immune status of the host. Hence, augmenting
      immunity by immunotherapeutic interventions may offer future directions to treat
      IFI. Expert opinion: A much better understanding of fungus and host cell
      interactions is essential for the development of safe and successful
      immunotherapeutic strategies. Indeed, there is encouraging preliminary data
      available that such approaches are possible; however, current data is too limited
      to allow solid conclusions on the risks and benefits in the clinical setting.
      Clinical trials focusing on the role of adjuvant immunotherapeutics with or
      without a combination of antifungals are highly needed for further evaluation.

PMID- 28429627
TI  - Compression therapy for congenital low-flow vascular malformations of the
      extremities: A systematic review.
AB  - Introduction Low-flow vascular malformations are congenital abnormalities of the
      veins, capillaries or lymphatic vessels or a combination of the previous.
      Compressive garments are frequently used as a first-line treatment option for low
      flow vascular malformations of the extremities with the purpose of relieving
      symptoms. Yet, the benefits and harms of compression stockings remain unclear.
      Methods A systematic search was performed in MEDLINE, Embase, Cochrane Central
      Register of Controlled Trials including a hand search for studies measuring the
      benefits and harms of compression garments in treating low-flow vascular
      malformations. Two investigators performed study selection, quality assessment
      and data extraction independently. Results Of the 565 studies found, eventually
      five (totalling 101 patients with venous malformations or Klippel-Trenaunay
      syndrome receiving compression therapy) observational studies were included in
      the systematic review. Although the overall quality of these studies was poor,
      results suggest that compression garments might lessen intravascular coagulation,
      improve symptoms and appearance, diminish oedema, and protect against minor
      trauma. None of the studies quantified any harms of compression therapy.
      Conclusion Even though compression therapy is commonly used in the treatment of
      low-flow vascular malformations, available literature does not provide high
      quality evidence to validate its use. We therefore advocate the need for
      prospective comparative trials with standardised outcome measures to study the
      benefits and harms of this treatment option.

PMID- 28429628
TI  - Relationship of Steroid Dosing and Duration of Mechanical Ventilation in Adult
      Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: The optimal steroid dose for patients who require mechanical
      ventilation (MV) for acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD) is unknown. OBJECTIVE: The primary objective of the study is to describe
      the relationship between steroid doses prescribed and duration of MV. METHODS:
      This was a retrospective study of patients admitted between October 2013 and
      September 2014 who were prescribed steroids and received MV for >=48 hours for
      AECOPD. RESULTS: Fifty-four patients were included in the study. Median
      maintenance daily dose of 300 mg/d (IQR: 150-300) prednisone equivalent was
      prescribed upon initiation of MV. The maintenance daily dose prescribed upon
      initiation of MV was visually plotted and was categorized into 2 groups: high
      dose (>=300 mg; n = 28) and low dose (<300 mg; n = 26). There was no relationship
      observed between the maintenance dose prescribed and duration of MV ( P = .44) or
      intensive care unit (ICU) length of stay (LOS; P = .63). Seventeen (31.5%)
      patients developed an infection during their hospital stay. These patients
      received a higher cumulative dose of steroids compared to those without an
      infection ( P = .035). CONCLUSION: No relationship was observed between
      maintenance steroid dose prescribed and the duration of MV or ICU LOS. Evaluation
      of a safe and effective dose and duration of steroids in this population is
      warranted.

PMID- 28429629
TI  - Developing indicators of appropriate and inappropriate end-of-life care in people
      with Alzheimer's disease, cancer or chronic obstructive pulmonary disease for
      population-level administrative databases: A RAND/UCLA appropriateness study.
AB  - BACKGROUND: A substantial amount of aggressive life-prolonging treatments in the
      final stages of life has been reported for people with progressive life
      shortening conditions. Monitoring appropriate and inappropriate end-of-life care
      is an important public health challenge and requires validated quality
      indicators. AIM: To develop indicators of appropriate and inappropriate end-of
      life care for people with cancer, chronic obstructive pulmonary disease or
      Alzheimer's disease, measurable with population-level administrative data.
      DESIGN: modified RAND/UCLA appropriateness method. SETTING/PARTICIPANTS:
      Potential indicators were identified by literature review and expert interviews
      and scored in a survey among three panels of experts (one for each disease
      group). Indicators for which no consensus was reached were taken into group
      discussions. Indicators with consensus among the experts were retained for the
      final quality indicator sets. RESULTS: The final sets consist of 28 quality
      indicators for Alzheimer's disease, 26 quality indicators for cancer and 27
      quality indicators for chronic obstructive pulmonary disease. The indicator sets
      measure aspects of aggressiveness of care, pain and symptom treatment, specialist
      palliative care, place of care and place of death and coordination and continuity
      of care. CONCLUSION: We developed a comprehensive set of quality indicators of
      appropriate and inappropriate end-of-life care in people with Alzheimer's
      disease, cancer or chronic obstructive pulmonary disease, to be used in
      population-level research. Our focus on administrative healthcare databases
      limits us to treatment and medication, excluding other important quality aspects
      such as communication, which can be monitored using complementary approaches.
      Nevertheless, our sets will enable an efficient comparison of healthcare
      providers, regions and countries in terms of their performance on appropriateness
      of end-of-life care.

PMID- 28429630
TI  - New and Emerging Risks Associated With "Green" Workplaces.
AB  - Work environments are continuously changing with the introduction of new
      technologies, substances and work processes, changes in the structure of the
      workforce and labor market, and new forms of employment and work organization.
      New work situations bring both risks and challenges for workers and employers,
      which, in turn, may require political, administrative, technical, and regulatory
      approaches to ensure worker safety and health. This article is based on a
      European Agency for Safety and Health at Work (EU-OSHA) report, Green Jobs and
      Occupational Safety and Health, that detailed new and emerging risks to
      occupational safety and health associated with new technologies in green jobs.
      Highlights from this report include key technologies in the bioindustry and new
      emerging risks associated with green jobs.

PMID- 28429631
TI  - Household food insecurity among people living with HIV in Sagamu, Nigeria: A
      preliminary study.
AB  - BACKGROUND: Household food insecurity has been associated with increased risk of
      transmission of HIV infection and poor treatment outcomes. This study therefore
      determined the prevalence of household food insecurity and its associated factors
      among people living with HIV in Sagamu, Ogun State, Nigeria. METHODS: A cross
      sectional descriptive study was carried out among 244 adult clients accessing
      care and support at the teaching hospital in Sagamu, Nigeria, selected via
      systematic sampling. Data was collected with the aid of a semi-structured,
      interviewer-administered questionnaire. Data was analysed using SPSS 21.0.
      Relevant descriptive and inferential statistics were calculated. Informed consent
      was obtained and strict confidentiality was ensured. RESULTS: The mean age of
      respondents was 38.8 +/- 9.2 years; 84% of respondents were female; 69.3% were
      married, 12.9% had lost their partners. About 12% spent more than three-quarters
      of the household income on food. The prevalence of household food insecurity was
      71.7%. Food insecurity was associated ( p < 0.05) with educational status;
      occupation; type of housing; availability of toilet facilities; benefiting from
      food assistance; delaying drugs to prevent hunger; skipping drugs; vegetable
      consumption pattern; and exchanging sex for food. CONCLUSION: The prevalence of
      household food insecurity in this study was high. Living conditions were
      significantly associated with food insecurity. Socio-economic conditions need to
      be improved, to optimize the health and food security status of people living
      with HIV in Sagamu.

PMID- 28429632
TI  - Comparison of piezoresistive sensor to PicoPress(r) in in-vitro interface
      pressure measurement.
AB  - Objective Interface pressure, the sine qua non for compression therapy, is rarely
      measured in clinical practice and scientific research. The goal of this study
      aimed to compare and examine the accuracy between a commercially available
      piezoresistive sensor and PicoPress(r) (Microlab, Padua, Italy) using the
      cylinder cuff model to measure in-vitro interface pressure. Method Ten
      piezoresistive sensors were calibrated using the National Institute of Standard
      and Technology certified manometer, and compared to PicoPress(r) using cylinder
      cuff model from 20 to 120 mmHg. Two statistical analyses were performed: (a) two
      sample t-test to compare the front to back surface of the piezoresistive sensors
      using mean pressure value and (b) one-sample paired t-test to compare the front
      and back surface of the piezoresistive sensors to PicoPress(r) and true pressure
      using mean pressure value. Result There was no difference in interface pressure
      measurement between the front and back surface of the piezoresistive sensors (P >
      0.05). Using mean pressure value, there was no significant difference between the
      front surface, back surface of the piezoresistive sensors, and PicoPress(r) (P >
      0.05). Standard deviation was larger for the piezoresistive sensors than
      PicoPress(r) at any given pressure and this difference was more pronounced in the
      higher pressure range. Conclusion Piezoresistive sensor may represent a viable
      alternative to PicoPress(r) in interface pressure measurement.

PMID- 28429633
TI  - The reliability of multidimensional neuropsychological measures: from alpha to
      omega.
AB  - OBJECTIVE: To demonstrate that Coefficient omega, a model-based estimate, is more
      a more appropriate index of reliability than coefficient alpha for the
      multidimensional scales that are commonly employed by neuropsychologists. METHOD:
      As an illustration, a structural model of an overarching general factor and four
      first-order factors for the WAIS-IV based on the standardization sample of 2200
      participants was identified and omega coefficients were subsequently computed for
      WAIS-IV composite scores. RESULTS: Alpha coefficients were >= .90 and omega
      coefficients ranged from .75 to .88 for WAIS-IV factor index scores, indicating
      that the blend of general and group factor variance in each index score created a
      reliable multidimensional composite. However, the amalgam of variance from
      general and group factors did not allow the precision of Full Scale IQ (FSIQ) and
      factor index scores to be disentangled. In contrast, omega hierarchical
      coefficients were low for all four factor index scores (.10-.41), indicating that
      most of the reliable variance of each factor index score was due to the general
      intelligence factor. In contrast, the omega hierarchical coefficient for the FSIQ
      score was .84. CONCLUSIONS: Meaningful interpretation of WAIS-IV factor index
      scores as unambiguous indicators of group factors is imprecise, thereby fostering
      unreliable identification of neurocognitive strengths and weaknesses, whereas the
      WAIS-IV FSIQ score can be interpreted as a reliable measure of general
      intelligence. It was concluded that neuropsychologists should base their clinical
      decisions on reliable scores as indexed by coefficient omega.

PMID- 28429634
TI  - Migration of oligomers from PET: determination of diffusion coefficients and
      comparison of experimental versus modelled migration.
AB  - Polyethylene terephthalate (PET) is increasingly used as food-contact material
      in, for example, containers for beverage such as bottles for soft drinks, mineral
      water, juices and beer. Mass transport of substances present in packaging
      materials into the packed food and beverages is monitored to verify the food law
      compliance of the materials. PET is known to contain or give rise to migrants
      that are oligomers derived from the polymeric material. Until now their actual
      migration potential has been investigated only poorly. A convenient way to
      determine their migration would be by using models. To verify existing models
      with experimental data, a migration kinetic study of PET oligomers was conducted.
      PET bottle material was submerged in 50% ethanol at 80 degrees C for 15 h. The
      oligomer content in the migration solutions was determined every hour using LC-MS
      with the first-series cyclic PET trimer as standard. Diffusion coefficients of
      five PET oligomers (first-series dimer and trimer, second-series dimer and
      trimer, and third-series dimer) were calculated from the obtained data and
      compared with the calculated diffusion coefficients using the models of Welle and
      Piringer. This is the first study to provide diffusion characteristics of
      oligomers in PET other than the first-series cyclic trimer.

PMID- 28429635
TI  - Congenital Hypothalamic "Hamartoblastoma" Versus "Hamartoma": Suggestions for
      Neuropathologic Terminology Emanating From a Mid-gestational Autopsy Case of
      Pallister-Hall Syndrome.
AB  - Pallister-Hall syndrome (PHS) is a rare malformative disorder that is due to
      truncating functional repressor mutations in GLI3. Since the seminal publication
      in 1980, hypothalamic tumors have been recognized to be a cardinal feature of
      PHS. In their original description of the neuropathologic features of PHS,
      Clarren et al. coined the term "hamartoblastoma" to characterize what they deemed
      to be a dual malformative and neoplastic mass of the hypothalamus. In subsequent
      published cases/series of PHS, the term "hamartoma" was often substituted for
      hamartoblastoma given what appeared to be a benign natural history of this
      lesion. Additional confusion in the literature has ensued since most hypothalamic
      hamartomas (HH) encountered on the clinical neuropathology service are "isolated"
      in nature (ie, no other congenital malformations) and present in a very different
      and stereotypical fashion with gelastic seizures and/or precocious puberty. While
      genomic investigations of isolated HH have begun to uncover a mutational profile
      of these cases, GLI3 mutations have only been recognized in a small subset of
      isolated HH. Herein, we describe the autopsy findings from a 21-week gestational
      age fetus with features of PHS. Moreover, we provide a detailed description of
      the hypothalamic tumor affecting this fetus and propose a novel subclassification
      of HH, distinguishing syndromic from isolated forms based upon the presence or
      absence of neocortical-like areas.

PMID- 28429636
TI  - Differences in game reading between selected and non-selected youth soccer
      players.
AB  - Applying an established theory of cognitive development-Skill Theory-the current
      study compares the game-reading skills of youth players selected for a soccer
      school of a professional soccer club (n = 49) and their non-selected peers (n =
      38). Participants described the actions taking place in videos of soccer game
      plays, and their verbalisations were coded using Skill Theory. Compared to the
      non-selected players, the selected players generally demonstrated higher levels
      of complexity in their game-reading, and structured the information of game
      elements-primarily the player, teammate and field-at higher complexity levels.
      These results demonstrate how Skill Theory can be used to assess, and distinguish
      game-reading of youth players with different expertise, a skill important for
      soccer, but also for other sports.

PMID- 28429637
TI  - Analysis of rotation angles and motions of the flexible mechanisms in bifurcated
      blood vessels.
AB  - This article investigates the relationship of rotation angle of two ends of
      elastic guidewires, and motion method of guidewires and catheters in bifurcated
      blood vessels. The relationship of rotation angles of the two ends of the
      guidewire has first been studied by mathematical reasoning, indicating that the
      rotation angle of the front end of guidewire can be precisely described by that
      of the rear end. In order to satisfy the requirements of different vascular
      interventional surgeries, we further investigated a general model of bifurcated
      human blood vessels. Based on this model, a new motion method, which ensures the
      guidewire and catheter move cooperatively along center lines of blood vessels to
      the final target point, has been introduced. Rotation angles of the guidewire in
      this model were then analyzed. By experiments to verify the functional
      relationship between rotation angles of two ends of guidewire, the motion method
      and algorithm of guidewire and catheter are correct. Our study provides
      references for future studies in fully automated vascular interventional
      surgeries.

PMID- 28429638
TI  - An Unusual Presentation of a Cervical Paraspinal Leiomyoma in an Adolescent
      Female.
AB  - Objective We describe an apparently unique case of an extra-uterine leiomyoma in
      the cervical paraspinal tissue including its evaluation and management. Methods A
      14-year-old girl was referred to the neurology clinic for an abnormal head CT
      following a concussion. MRI revealed a homogenously enhancing left cervical
      paraspinal mass. The patient underwent complete resection and subsequent genetic
      testing and counseling were obtained to determine the presence of Li-Fraumeni
      Syndrome (LFS) or Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)
      mutations. Result Histopathological examination proved that the tumor was a
      benign leiomyoma. Genomic testing for Fumarate Hydratase Gene, HLRCC, TP53
      mutations or deletions, and LFS sequencing were negative. Further testing showed
      no immunosuppression. Conclusions To the best of our knowledge, this is the only
      case of paraspinal leiomyoma to have been reported to date. We emphasize the
      importance of considering immunosuppression, LFS, or HLRCC as an underlying cause
      in extra-uterine leiomyata.

PMID- 28429639
TI  - Review of doing Bayesian data analysis: a tutorial with R, JAGS, and Stan (second
      edition).

PMID- 28429640
TI  - Spinal Alterations of Reil Insula in Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease that involves
      numerous cellular and biochemical mechanisms resulting in synaptic alterations
      and extensive neuronal loss. It is primarily characterized by impairment of
      memory, associated frequently with mood disorders. Continuous studies have shown
      that insula may be an important target of AD, but neuropathological alterations
      have not been described extensively. In the present study, we attempted to
      describe the morphometric and morphological changes of the spines of Reil insula
      in AD in comparison with normal aging using a silver impregnation technique. We
      classified spines into 3 types: (1) long neck, (2) short stubby, and (3) other
      types; and we measured and correlated the length of them in normal controls and
      in individuals with AD using ImageJ application. Statistical analysis was based
      on the Student t test on the basis of 360 cells in SPSS v.17.0, and significance
      was taken as P < .05.

PMID- 28429641
TI  - Indoor Air Temperature and Agitation of Nursing Home Residents With Dementia.
AB  - This study aimed to determine the specific correlation between indoor air
      temperature and agitation of nursing home residents with dementia. Agitated
      behaviors of 21 residents, living in 1 nursing home, were assessed for a 10-month
      period using the Cohen-Mansfield Agitation Inventory (CMAI). The CMAI Total
      Frequency scores were found to increase significantly when indoor average
      temperatures deviated from 22.6 degrees C. In addition, cumulative exposure to
      temperatures higher than 26 degrees C and lower than 20 degrees C was linearly
      correlated with CMAI Total Frequency scores. Results showed that agitated
      behaviors not only affected the person manifesting them but were found to be
      disruptive for other residents and the delivery of care. Agitation can,
      therefore, be potentially reduced by limiting the range of indoor air temperature
      variations, and aged care providers should ensure that a thermally comfortable
      environment is provided in nursing homes to enhance comfort and well-being of all
      occupants.

PMID- 28429642
TI  - Selected weight management interventions for military populations in the United
      States: a narrative report.
AB  - Overweight and obesity continues to be a significant public health burden in the
      US and particularly among military personnel. Although the US Department of
      Defense mandates standardized physical activity requirements for military
      members, incidence and prevalence of overweight and obesity among military
      personnel continue to increase. Each military department controls their own
      interventional strategies for physical fitness and weight control. However,
      unique challenges such as geographic transients, lack of central standardization
      and empirical efficacy data across military departments, and chronic stress
      associated with military service adversely affect program outcomes. This brief
      narrative report explores overweight and obesity interventions among military
      populations from 2006 to 2016 and includes programmatic reviews of eight
      overweight and obesity interventions: The Prevention of Obesity in Military
      Community; Health Eating, Activity, and Lifestyle Training Headquarters
      (H.E.A.L.T.H); ArmyMOVE!; L.I.F.E.; Look AHEAD; Nutrition-focused Wellness
      Coaching; Go for Green; and LE3AN. A majority of these interventions did not
      report significant weight loss 6 months post intervention, and did not mention a
      theoretical foundation within the interventions. Further research to examine the
      importance of theory-based programming is warranted to improve process and
      outcome objectives.

PMID- 28429643
TI  - Emergency department staff priorities for improving palliative care provision for
      older people: A qualitative study.
AB  - BACKGROUND: Emergency department-based palliative care services are increasing,
      but research to develop these services rarely includes input from emergency
      clinicians, jeopardizing the effectiveness of subsequent palliative care
      interventions. AIM: To collaboratively identify with emergency clinicians'
      improvement priorities for emergency department-based palliative care for older
      people. DESIGN: This was one component of an experience-based co-design project,
      conducted using semi-structured interviews and feedback sessions.
      SETTING/PARTICIPANTS: In-depth interviews with 15 emergency clinicians (nurses
      and doctors) at a large teaching hospital emergency department in the United
      Kingdom exploring experiences of palliative care delivery for older people. A
      thematic analysis identified core challenges that were presented to 64 clinicians
      over five feedback sessions, validating interview findings, and identifying
      shared priorities for improving palliative care delivery. RESULTS: Eight
      challenges emerged: patient age; access to information; communication with
      patients, family members, and clinicians; understanding of palliative care; role
      uncertainty; complex systems and processes; time constraints; and limited
      training and education. Through feedback sessions, clinicians selected four
      challenges as improvement priorities: time constraints; communication and
      information; systems and processes; and understanding of palliative care. As
      resulting improvement plans evolved, "training and education" replaced "time
      constraints" as a priority. CONCLUSION: Clinician priorities for improving
      emergency department-based palliative care were identified through collaborative,
      iterative processes. Though generally aware of older palliative patients' needs,
      clinicians struggled to provide high-quality care due to a range of complex
      factors. Further research should identify whether priorities are shared across
      other emergency departments, and develop, implement, and evaluate strategies
      developed by clinicians.

PMID- 28429645
TI  - Homestead Food Production and Maternal and Child Dietary Diversity in Nepal:
      Variations in Association by Season and Agroecological Zone.
AB  - BACKGROUND: Suaahara, a large-scale integrated program, aimed to improve diets
      and nutritional status among women and children, in part by facilitating enhanced
      homestead food production (EHFP). OBJECTIVE: This study examines associations
      between EHFP and maternal and child dietary diversity and variations by season
      and agroecological zone (AEZ): mountains and terai. METHODS: We used data from
      household monitoring surveys (n = 2101 mothers; n = 994 children, 6-23 months),
      which included a 7-day dietary recall and maternal report on participation in 5
      EHFP activities-received vegetable seeds, chicks, and technical support and
      participated in training and EHFP groups. We constructed binary variables for
      each activity and a scale (0-5) summing participation. For dietary diversity, we
      used the Women's Dietary Diversity Score using 10 food groups and 7 food groups
      for child diets. Multivariable linear regression analyses were used to assess
      associations between EHFP participation and dietary diversity by season and AEZ,
      controlling for potential confounders and clustering. RESULTS: In adjusted
      models, we found positive associations between dietary diversity and chicks,
      technical support, and EHFP beneficiary groups; the magnitude of the associations
      varied by season and AEZ. The degree of participation in 5 EHFP activities was
      positively associated with maternal dietary diversity in the terai (beta = .24, P
      < .001) and mountains (beta = .12, P = .01) and child dietary diversity in the
      terai (beta = .35, P < .001) during the winter. No associations were found in the
      rainy season. CONCLUSION: Our findings highlight the potential for EHFP to
      address dietary diversity constraints among this population. Variation by
      subnational setting and seasonality suggest that policies and programs should be
      contextualized.

PMID- 28429644
TI  - A systematic review of discomfort due to toe or ear clipping in laboratory
      rodents.
AB  - Toe clipping and ear clipping (also ear notching or ear punching) are frequently
      used methods for individual identification of laboratory rodents. These
      procedures potentially cause severe discomfort, which can reduce animal welfare
      and distort experimental results. However, no systematic summary of the evidence
      on this topic currently exists. We conducted a systematic review of the evidence
      for discomfort due to toe or ear clipping in rodents. The review methodology was
      pre-specified in a registered review protocol. The population, intervention,
      control, outcome (PICO) question was: In rodents, what is the effect of toe
      clipping or ear clipping, compared with no clipping or sham clipping, on welfare
      related outcomes? Through a systematic search in PubMed, Embase, Web of Science
      and grey literature, we identified seven studies on the effect of ear clipping on
      animal welfare, and five such studies on toe clipping. Studies were included in
      the review if they contained original data from an in vivo experiment in rodents,
      assessing the effect of toe clipping or ear clipping on a welfare-related
      outcome. Case studies and studies applying unsuitable co-interventions were
      excluded. Study quality was appraised using an extended version of SYstematic
      Review Centre for Laboratory animal Experimentation (SYRCLE)'s risk of bias tool
      for animal studies. Study characteristics and outcome measures were highly
      heterogeneous, and there was an unclear or high risk of bias in all studies. We
      therefore present a narrative synthesis of the evidence identified. None of the
      studies reported a sample size calculation. Out of over 60 different outcomes, we
      found evidence of discomfort due to ear clipping in the form of increased
      respiratory volume, vocalization and blood pressure. For toe clipping, increased
      vocalization and decreased motor activity in pups were found, as well as long
      term effects in the form of reduced grip strength and swimming ability in adults.
      In conclusion, there is too little evidence to reliably assess discomfort due to
      toe or ear clipping, and the quality of the available evidence is uncertain.
      Adequately powered, high-quality studies reporting reliable, relevant outcome
      measures are needed to accurately assess the impact of these identification
      techniques. Until more reliable evidence is available, any effect of toe clipping
      or ear clipping on animal welfare and study results cannot be confirmed or
      excluded.

PMID- 28429646
TI  - Rule-violations sensitise towards negative and authority-related stimuli.
AB  - Rule violations have usually been studied from a third-person perspective,
      identifying situational factors that render violations more or less likely. A
      first-person perspective of the agent that actively violates the rules, on the
      other hand, is only just beginning to emerge. Here we show that committing a rule
      violation sensitises towards subsequent negative stimuli as well as subsequent
      authority-related stimuli. In a Prime-Probe design, we used an instructed rule
      violation task as the Prime and a word categorisation task as the Probe. Also, we
      employed a control condition that used a rule inversion task as the Prime
      (instead of rule violations). Probe targets were categorised faster after a
      violation relative to after a rule-based response if they related to either,
      negative valence or authority. Inversions, however, primed only negative stimuli
      and did not accelerate the categorisation of authority-related stimuli. A
      heightened sensitivity towards authority-related targets thus seems to be
      specific to rule violations. A control experiment showed that these effects
      cannot be explained in terms of semantic priming. Therefore, we propose that rule
      violations necessarily activate authority-related representations that make rule
      violations qualitatively different from simple rule inversions.

PMID- 28429647
TI  - Malignant Rhabdoid Tumor of Soft Tissue.
AB  - Introduction Malignant rhabdoid tumor (MRT) is defined as a high-grade sarcoma
      derived from an uncertain cell of origin. Its diagnosis is associated with poor
      prognosis and patient's life expectancy is greatly reduced. Material and method
      Here, we describe a unique case of 9-month-old boy who presented with a large MRT
      arising from the soft tissue of the neck. Following intensive multimodal
      treatment, the patient benefited from a 25 years' remission until the discovery
      of multiple liver metastases. Conclusion MRT of soft tissue needs to be
      distinguished from other soft tissue neoplasms, as MRT is highly aggressive and
      is usually associated with a poor outcome. In addition, this is the longest
      remission time reported in a patient with soft tissue MRT and this might be
      related to the use of early intensive multimodal treatments.

PMID- 28429648
TI  - -The Influence of Scene Context on Parafoveal Processing of Objects.
AB  - Many studies in reading have shown the enhancing effect of context on the
      processing of a word before it is directly fixated (parafoveal processing of
      words; Balota et al., 1985; Balota & Rayner, 1983; Ehrlich & Rayner, 1981). Here,
      we examined whether scene context influences the parafoveal processing of objects
      and enhances the extraction of object information. Using a modified boundary
      paradigm (Rayner, 1975), the Dot-Boundary paradigm, participants fixated on a
      suddenly-onsetting cue before the preview object would onset 4 degrees  away. The
      preview object could be identical to the target, visually similar, visually
      dissimilar, or a control (black rectangle). The preview changed to the target
      object once a saccade toward the object was made. Critically, the objects were
      presented on either a consistent or an inconsistent scene background. Results
      revealed that there was a greater processing benefit for consistent than
      inconsistent scene backgrounds and that identical and visually similar previews
      produced greater processing benefits than other previews. In the second
      experiment, we added an additional context condition in which the target location
      was inconsistent, but the scene semantics remained consistent. We found that
      changing the location of the target object disrupted the processing benefit
      derived from the consistent context. Most importantly, across both experiments,
      the effect of preview was not enhanced by scene context. Thus, preview
      information and scene context appear to independently boost the parafoveal
      processing of objects without any interaction from object-scene congruency.

PMID- 28429649
TI  - Fundic Gland Polyps in the Pediatric Population: Clinical and Histopathologic
      Studies.
AB  - We retrospectively studied the clinical and histologic features of pediatric
      fundic gland polyps (FGPs) in 16 patients. FGPs had an endoscopic prevalence of
      0.25% in 8527 pediatric gastric biopsies. Five patients had familial adenomatous
      polyposis (FAP). The median age of onset was 17.7 years in FAP and 17.3 years in
      sporadic patients. All syndromic patients were asymptomatic and FGPs were
      identified during surveillance for existing or concurrent colon polyps. They did
      not take antacids. In comparison, all 11 sporadic FGPs were identified during
      evaluation of symptomatic patients who had taken antacids (median duration 21
      months). Syndromic FGPs can be multiple at single endoscopy and were more likely
      to recur, while sporadic FGPs were often single. None of the sporadic patients
      had recurrence of FGPs or a subsequent diagnosis of FAP during a median follow-up
      of 20.5 months. The dilated fundic glands were lined by parietal and chief cells
      only in a majority (22/41, 53.7%) of syndromic FGPs, while additional tall
      mucinous lining cells were found in all sporadic FGPs. Syndromic FGPs did not
      have parietal cell hypertrophy in the background oxyntic mucosa. Nuclear
      immunopositivity for beta-catenin was essentially absent in all the FGPs. In
      conclusion, FGPs were rare in pediatric patients. In syndromic patients, FGPs are
      asymptomatic and did not precede colon polyps. Prolonged antacid intake seems to
      be associated with development of sporadic FGPs. Cellular components of dilated
      fundic glands and background parietal cell hypertrophy can be useful features to
      eliminate concern for syndromic polyposis.

PMID- 28429650
TI  - Development of real-time PCR tests for the detection of Tenebrio molitor in food
      and feed.
AB  - Insects are rich in proteins and could be an alternative source of proteins to
      feed animals and humans. Numerous companies have started the production of
      insects for feed purposes. In Europe, these processed animal proteins are not yet
      authorised by legislation as many questions still need to be answered concerning
      this 'novel food'. Authorisations will be possible when methods of authentication
      of the products are available. In this study we propose real-time PCR methods for
      the specific detection of the mealworm (Tenebriomolitor), one of the most widely
      used insects for food and feed production. Two PCR assays are proposed: the first
      based on the wingless gene and the second based on the cadherin gene. The PCR
      tests amplify fragments of 87 bp. These qualitative methods were tested according
      to several performance criteria. The specificity was tested on 34 insect species'
      DNA, but also on non-insect species including crustacean, mammals, birds and
      plants. The limit of detection was determined and was below 20 copies for the two
      PCR tests. The applicability of the tests was demonstrated by the analysis of
      real-life processed samples containing T. molitor.

PMID- 28429651
TI  - Time to improve statin prescription guidelines in low-risk patients?
AB  - Background The challenge of the primary prevention of cardiovascular disease
      (CVD) is to identify patients who would benefit from treatment with statins.
      Statins are currently prescribed to many patients, even those at a low 10-year
      risk of CVD. These latter patients may not be eligible for statins according to
      current guidelines. Design This study investigated the prescription of guideline
      consistent (according to guidelines) and guideline-inconsistent (not according to
      guidelines) lipid-lowering treatment in primary prevention in a large
      contemporary Dutch cohort study (Lifelines). Methods Lifelines is a large cohort
      study from the Netherlands. Participants were recruited between 2006 and 2013.
      They completed questionnaires and underwent a physical examination. Participants
      with previous CVD were excluded. Statins and ezetimibe were grouped as statin
      treatment. The Dutch guideline on cardiovascular management was used to assess
      eligibility for statins. Results Of 147,785 participants, 7092 (4.8%) reported
      statin treatment. In 4667 (66%) participants, statin treatment was inconsistent
      with the Dutch guideline. A total of 78% of these participants had a low 10-year
      predicted CVD risk. Multivariable logistic regression analysis showed that female
      sex and smoking were strongly associated with guideline-inconsistent treatment.
      Interestingly, 65% of the these participants had low-density lipoprotein
      cholesterol levels above the 95th percentile, adjusted for age and sex, two or
      more major risk factors of CVD or a positive family history of premature CVD.
      Therefore treatment might be reasonable. Conclusions There is a large
      inconsistency between guideline recommendations and the prescription of statins
      in clinical practice in the Netherlands. This is especially true for patients
      with low CVD risk. Many of these patients probably had risk-increasing
      circumstances justifying treatment.

PMID- 28429655
TI  - Corrigendum.

PMID- 28429652
TI  - Atypical regulators of Wnt/beta-catenin signaling as potential therapeutic
      targets in Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma is one of the most common causes of cancer-related death
      worldwide. Hepatocellular carcinoma development depends on the inhibition and
      activation of multiple vital pathways, including the Wnt signaling pathway. The
      Wnt/beta-catenin pathway lies at the center of various signaling pathways that
      regulate embryonic development, tissue homeostasis and cancers. Activation of the
      Wnt/beta-catenin pathway has been observed frequently in hepatocellular
      carcinoma. However, activating mutations in beta-catenin, Axin and Adenomatous
      Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation
      observed in hepatocellular carcinoma. Therefore, besides mutations in the
      canonical Wnt components, there must be additional atypical regulation or
      regulators during Wnt signaling activation that promote liver carcinogenesis. In
      this mini-review, we have tried to summarize some of these well-established
      factors and to highlight some recently identified novel factors in the Wnt/beta
      catenin signaling pathway in hepatocellular carcinoma. Impact statement Early
      recurrence of human hepatocellular carcinoma (HCC) is a frequent cause of poor
      survival after potentially curative liver resection. Among the deregulated
      signaling cascades in HCC, evidence indicates that alterations in the Wnt/beta
      catenin signaling pathway play key roles in hepatocarcinogenesis. In this review,
      we summarize the potential molecular mechanisms how the microtubule-associated
      Protein regulator of cytokinesis 1 (PRC1), a direct Wnt signaling target
      previously identified in our laboratory to be up-regulated in HCC, in promoting
      cancer proliferation, stemness, metastasis and tumorigenesis through a complex
      regulatory circuitry of Wnt3a activities.

PMID- 28429653
TI  - Clinical development of fenretinide as an antineoplastic drug: Pharmacology
      perspectives.
AB  - Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against
      cancer cells. Despite substantial in vitro cytotoxicity, response rates in early
      clinical trials with 4-HPR have been less than anticipated, likely due to the low
      bioavailability of the initial oral capsule formulation. Several clinical studies
      have shown that the oral capsule formulation at maximum tolerated dose (MTD)
      achieved <10 umol/L concentrations in patients. To improve bioavailability of 4
      HPR, new oral powder (LYM-X-SORB(r), LXS) and intravenous lipid emulsion (ILE)
      formulations are being tested in early-phase clinical trials. ILE 4-HPR
      administered as five-day continuous infusion achieved over 50 umol/L at MTD with
      minimal systemic toxicities; multiple complete and partial responses were
      observed in peripheral T cell lymphomas. The LXS oral powder 4-HPR formulation
      increased plasma levels approximately two-fold at MTD in children without dose
      limiting toxicities and demonstrated multiple complete responses in recurrent
      neuroblastoma. The clinical activity observed with new 4-HPR formulations is
      attributed to increased bioavailability. Phase I and II clinical trials of both
      LXS 4-HPR and ILE 4-HPR are in progress as a single agent or in combination with
      other drugs. Impact statement One of the critical components in drug development
      is understanding pharmacology (especially pharmacokinetics) of the drugs being
      developed. Often the pharmacokinetic properties, such as poor solubility leading
      to poor bioavailability, of the drug can limit further development of the drug.
      The development of numerous drugs has often halted at clinical testing stages,
      and several of them were due to the pharmacological properties of the agents,
      resulting in increased drug development cost. The current review provides an
      example of how improved clinical activity can be achieved by changing the
      formulations of a drug with poor bioavailability. Thus, it emphasizes the
      importance of understanding pharmacologic characteristics of the drug in drug
      development.

PMID- 28429657
TI  - What happened first? Working memory and negative emotion tell you better:
      evidence from a temporal binding task.
AB  - Emotionally arousing events may disrupt the ability to bind together different
      features of items to their context; this holds true both for spatial binding
      (i.e. remembering the locations of previously presented items) and temporal
      binding (i.e. remembering the order in which different items were previously
      presented). Nonetheless, memory for emotional events may be enhanced in certain
      situations. A key factor that might explain the memory-emotion relation is
      represented by individual differences in cognition. The present study
      investigated temporal binding for neutral and negative events in a group of 50
      undergraduate students, focusing on the role of individual differences in working
      memory (measured through forward and backward digit span tasks). Temporal binding
      was assessed with sorting accuracy of various pictorial scripted events, 24 h
      after encoding. Results showed that higher backward digit span predicted higher
      binding accuracy; importantly, this was qualified by the interaction with
      valence, such that higher backward digit span predicted better performance for
      negative, but not neutral, events. It is concluded that working memory
      facilitates binding of emotional events to their temporal context during
      encoding, creating a strong representation, and favouring later retrieval of such
      bound representations.

PMID- 28429654
TI  - MicroRNA-451 regulates chemoresistance in renal cell carcinoma by targeting ATF-2
      gene.
AB  - Renal cell carcinoma (RCC) is a malignant tumor, which severely threatens human's
      life, moreover, the multi-drug resistance (MDR) under RCC undoubtedly strengthen
      the difficulties in the treatment. MiR-451 has been considered to play an
      important role in regulation of MDR in several cancers, but the role of it in MDR
      of RCC has not been explored. This study aims to explore the mechanism of miR-451
      as a target to regulate chemotherapy resistance, which is crucial for further
      exploring novel therapy for RCC. Two human cell lines (ACHN and GRC-1) were
      performed in this study and adriamycin (ADM) was used to construct MDR cell
      lines. qRT-PCR was used to determine the mRNA expression of miR-451 and ATF-2.
      Weston blot was used to determine protein expression. MTT assay and flow
      cytometry were used for assessing cell viability and apoptosis, individually.
      Luciferase reporter assay was used to detect the targeting of miR-451 and ATF-2.
      Results presented that the expression of miR-451 was higher in low MDR cell line
      (ACHN) comparing with the high MDR cell line (GRC-1), while the expression of ATF
      2 revealed an opposite results. MiR-451 targeted ATF-2 and regulated its
      expression. Overexpression of miR-451 strengthened drug resistance, decreased
      cell viability, and increased cell apoptosis of GRC-1 pretreated by ADM, while
      overexpressed ATF-2 reversed the effect induced by miR-451 overexpression. Then
      miR-451 knockdown improved drug susceptibility, decreased cell apoptosis, and
      increased cell viability of ACHN induced by ADM, however, ATF-2 suppression
      reversed the low rate of cell apoptosis and high rate of cell viability induced
      by miR-451 knockdown. Our results revealed that miR-451 regulates the drug
      resistance of RCC by targeting ATF-2 gene, which might be critical for overcoming
      MDR in RCC patients. Impact statement This is the first study to emphasize the
      expression of miR-451 on regulating multi-drug resistance (MDR) in renal cell
      carcinoma (RCC). Our study found that miR-451 regulates the drug resistance of
      RCC by targeting ATF-2, which might be critical for overcoming MDR in RCC
      patients. This study not only provides solid theory foundation for the clinical
      therapy, but also offers unique insights for the further RCC research.
      Furthermore, the study helps us to understand the mechanism of MDR, which was
      crucial for identifying the chemoresistance on several related tumors.

PMID- 28429656
TI  - Baseline cognitive test performance and concussion-like symptoms among adolescent
      athletes with ADHD: examining differences based on medication use.
AB  - OBJECTIVE: Youth with attention deficit hyperactivity disorder (ADHD) perform
      more poorly on preseason cognitive testing and report more baseline concussion
      like symptoms but prior studies have not examined the influence of medication use
      on test performance or symptom reporting. This study investigated whether
      medication use is relevant when interpreting baseline ImPACT(r) results from
      student athletes with ADHD. METHOD: Participants were 39,247 adolescent athletes,
      ages 13-18 (mean age = 15.5 years, SD = 1.3), who completed baseline cognitive
      testing with ImPACT(r). The sample included slightly more boys (54.4%) than
      girls. Differences in ImPACT(r) composite scores and concussion-like symptom
      reporting (between ADHD/No medication, ADHD/Medication, No ADHD/Medication, and
      Control groups) were examined with ANOVAs, conducted separately by gender.
      RESULTS: In this large, state-wide data-set, youth with ADHD had greater rates of
      invalid ImPACT results compared to control subjects (ADHD/No Medication: girls =
      10.9%, boys = 10%; ADHD/Medication: girls = 8.1%, boys = 9.1%; Controls: girls =
      5.2%, boys = 6.7%). Groups differed across all ImPACT(r) composites (invalid
      profiles were removed), in the following order (from worse to better
      performance): ADHD/No Medication, ADHD/Medication, and Control participants.
      Pairwise effect sizes indicated that the largest differences were on the Visual
      Motor Speed composite, with the ADHD/No medication group performing worse than
      the ADHD/Medication group and the Controls. The ADHD/Medication group did not
      differ meaningfully from Controls on any composite, for either sex (d = 0 to
      .19). The ADHD groups did not differ on total symptom scores but both ADHD groups
      endorsed significantly more symptoms compared to Controls. CONCLUSIONS: Contrary
      to our hypothesis, we found medication use had only a subtle effect on cognitive
      performance and no significant effect on concussion-like symptom reporting.
      Student athletes reporting medication use for ADHD performed comparably to
      student athletes with no ADHD on baseline testing.

PMID- 28429658
TI  - Sex differences in utilization and outcomes of catheter-directed thrombolysis in
      patients with proximal lower extremity deep venous thrombosis - Insights from the
      Nationwide Inpatient Sample.
AB  - Catheter-directed thrombolysis (CDT) is being increasingly used for the treatment
      of proximal lower extremity (LE) deep venous thrombosis (DVT). However, sex
      differences in utilization and safety outcomes of CDT in these patients are
      unknown. The Nationwide Inpatient Sample (NIS) database was used to identify all
      patients with a principal discharge diagnosis of proximal LE or caval DVT who
      underwent CDT between January 2005 and December 2011 in the United States. We
      evaluated the comparative safety outcomes of CDT among a propensity-matched group
      of 1731 men versus 1731 women. Among 108,243 patients with proximal LE or caval
      DVT, 4826 patients (4.5%) underwent CDT. Overall, women underwent CDT less often
      compared to men (4.1% vs 4.9%, p<0.01, respectively). The rates of CDT increased
      between 2005 and 2011 for both women (2.1% to 5.9%, p<0.01) and men (2.5% to
      7.5%, p<0.01). There was no significant difference in in-hospital mortality (1.2%
      vs 1.3%, p=0.76). Women were noted to have higher rates of blood transfusions
      (11.7% vs 8.8%, p<0.01), but lower rates of intracranial hemorrhage (0.5% vs
      1.2%, p=0.03) and gastrointestinal bleeding (0.9% vs 2.2%, p<0.01) compared with
      men. Women were more likely to undergo inferior vena cava filter placement (37.0%
      vs 32.1%, p<0.01). In this large nationwide cohort, women with proximal DVT were
      less likely to receive CDT compared to men. Although mortality rates were
      similar, women were noted to have higher blood transfusion rates while men had
      more episodes of intracranial and gastrointestinal bleeding.

PMID- 28429659
TI  - Sex differences in disease-specific health status measures in patients with
      symptomatic peripheral artery disease: Data from the PORTRAIT study.
AB  - Peripheral artery disease (PAD) is associated with poor health status (symptoms,
      functioning, quality of life (QOL)). Whether sex differences exist in PAD
      specific health status is unknown. In patients presenting to a specialty clinic
      with new-onset or recent exacerbation of PAD, we examined sex differences as
      assessed by the Peripheral Artery Questionnaire (PAQ). The Patient-centered
      Outcomes Related to TReatment Practices in Peripheral Arterial Disease:
      Investigating Trajectories (PORTRAIT) study is a multicenter, international
      prospective study of patients with new or worsening PAD symptoms. Baseline
      characteristics and mean PAQ scores were compared among women ( n=481) and men (
      n=793) before they underwent treatment. The independent association of sex with
      health status was assessed with multivariable linear regression. As compared with
      men, women were less often Caucasian, married and employed, and more often
      lacking health insurance, living alone (36.2% vs 23.6%, p<0.001), had depression
      and avoided care due to cost (17.0% vs 12.3%, p=0.018). Women and men were of a
      similar age and education level, and had similar ankle-brachial index (ABI)
      values (0.7 +/- 0.2 in both groups, p=0.052). Female sex was independently
      associated with lower PAQ scores on all domains (physical functioning adjusted
      mean difference of -8.40, p<0.001; social functioning adjusted mean difference of
      -6.8, p<0.001; QOL adjusted mean difference of -6.7, p<0.001), although no
      differences were observed in treatment satisfaction (adjusted mean difference 
      0.20, p=0.904). Despite similar ABIs, women presenting with symptoms of PAD had
      poorer PAD-specific functioning as compared with men, impacting all major health
      status domains, independent of socio-economic and clinical characteristics.

PMID- 28429660
TI  - Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA
      patients.
AB  - Sex affects the presentation, treatment, and outcomes of abdominal aortic
      aneurysm (AAA). Although AAAs are less prevalent in women, at least in the
      general population, women with an AAA have a poorer prognosis in comparison to
      men. Sex differences in the genetic predisposition for aneurysm disease remain to
      be established. In this study we investigated the familial risk of AAA for women
      compared to men. All living AAA patients included in a 2004-2012 prospective
      database were invited to the multidisciplinary vascular/genetics outpatient
      clinic between 2009 and 2012 for assessment of family history using detailed
      questionnaires. AAA risk for male and female relatives was calculated separately
      and stratified by sex of the AAA patients. Families of 568 AAA patients were
      investigated and 22.5% of the patients had at least one affected relative. Female
      relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the
      estimated sex-specific population risk. Relatives of female AAA patients had a
      higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022),
      corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and
      male relatives, respectively. The risk for aortic aneurysm in relatives of AAA
      patients is higher than expected from population risk. The excess risk is highest
      for the female relatives of AAA patients and for the relatives of female AAA
      patients. These findings endorse targeted AAA family screening for female and
      male relatives of all AAA patients.

PMID- 28429661
TI  - Understanding sex differences in health status: A frontier in the field of
      vascular medicine.

PMID- 28429662
TI  - Pregnancy, contraception and venous thromboembolism (deep vein thrombosis and
      pulmonary embolism).

PMID- 28429663
TI  - Finding the groove: The groove sign in scleroderma and related disorders.

PMID- 28429664
TI  - Alternative causes of myocardial ischemia in women: An update on spontaneous
      coronary artery dissection, vasospastic angina and coronary microvascular
      dysfunction.
AB  - Although coronary obstruction due to atherosclerosis is the most common cause of
      myocardial ischemia, a significant proportion of patients have myocardial
      ischemia in the absence of obstructive epicardial coronary artery disease (CAD).
      This finding is more common among women and alternative causes can mediate
      myocardial ischemia. Abnormalities in vascular structure, alterations in coronary
      vasomotion and dysfunction of the coronary microcirculation can all cause
      ischemia in the absence of obstructive CAD due to atherosclerosis. In this
      review, we provide an update on three alternative causes of myocardial ischemia:
      spontaneous coronary artery dissection (SCAD), vasospastic angina (VSA) and
      coronary microvascular dysfunction (CMVD). We review pathophysiology, clinical
      presentation, diagnosis, treatment and outcomes related to these important
      clinical entities. There is increasing interest in better defining this patient
      population with use of advanced imaging and testing tools. Despite the increased
      associated risk with future cardiac events, evidence-based treatments for these
      diagnoses remain under-studied and poorly defined. These alternative diagnoses
      should be kept in mind when evaluating women with myocardial ischemia without
      obstructive CAD due to atherosclerosis.

PMID- 28429665
TI  - The 2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity
      Peripheral Artery Disease: An interview with SVM members of the writing
      committee.

PMID- 28429666
TI  - Unlocking the phenotype of aneurysm disease: Are women the key?

PMID- 28429667
TI  - Sex-based disparities in venous thromboembolism outcomes: A National Inpatient
      Sample (NIS)-based analysis.
AB  - Venous thromboembolism (VTE) contributes to significant morbidity, mortality, and
      socioeconomic burden. There is a paucity of literature regarding sex-based
      sociodemographic differences in VTE presentation and short-term outcomes. We
      aimed to compare clinical outcomes between men and women hospitalized for VTE
      management. We performed a retrospective analysis using data from the National
      Inpatient Sample (NIS) database from 2012 to 2013. Inclusion criteria were age 18
      years and older and a primary discharge diagnosis of VTE. Sociodemographic
      features and medical comorbidities were analyzed, as were hospital length of stay
      and in-hospital mortality rates. A total of 107,896 patients met the inclusion
      criteria; 53% were female. Median age was 65 years (interquartile range 51-77)
      and women were older than men (65 vs 62 years, p<0.001). There were significant
      differences between men and women with respect to race, primary insurance payer
      and medical comorbidities, and small differences with respect to VTE location.
      Female sex was associated with a small but significantly longer hospital length
      of stay (mean ratio 1.04, 95% CI 1.03-1.05, p<0.001) but no significant
      difference in in-hospital mortality (2.2% vs 2.1%, p=0.15). In a multivariate
      model, there was no significant difference between women and men with respect to
      hospital length of stay or in-hospital mortality. In conclusion, we used data
      from the NIS to study over 100,000 patients hospitalized for VTE, and identified
      several sex-based disparities in sociodemographic factors and location of VTE.
      However, in a multivariable analysis correcting for these factors, sex was not
      associated with significant differences in clinical outcomes.

PMID- 28429668
TI  - The Role of Mitochondria-Associated Reactive Oxygen Species in the Amyloid beta
      Induced Production of Angiogenic Factors b y ARPE-19 Cells.
AB  - OBJECTIVE: This study aimed to investigate the mechanisms whereby Amyloidbeta
      (Abeta) induces the production of angiogenic factors by a human retinal pigment
      epithelial cell line (ARPE-19) cells. METHODS: ARPE-19 cells obtained from the
      American Type Culture Collection (ATCC) were utilized in this study. The
      expression level of vascular endothelial growth factor (VEGF), Interleukin-8 (IL
      8), monocyte chemoattractant protein-1 (MCP-1) and complement activation
      fragments C3a and C5a were measured by Real-time quantitative PCR (RT-PCR) and
      Enzyme-linked immunosorbent assay (ELISA). The production of mitochondria
      associated reactive oxygen species (ROS) was measured by flow cytometry. RESULTS:
      The expression of VEGF, IL-8, MCP-1, C3a and C5a was significantly increased in
      Abeta-treated ARPE-19 cells. Mitochondria-associated ROS production was also
      significantly increased when exposed to Abeta. Inhibition of mitochondrial ROS
      with Diphenyleneiodonium chloride (DPI) markedly decreased the Abeta induced
      production of VEGF, IL-8, MCP-1, C3a and C5a by ARPE-19 cells. Anti-C3a or anti
      C5a neutralizing antibodies did not have a detectable influence on the secretion
      of VEGF, IL-8 and MCP-1 by ARPE-19 cells upon stimulation with Abeta. CONCLUSION:
      Our results support the hypothesis that Abeta is involved in the pathogenesis of
      choroidal neovascularization (CNV) formation by promoting the production of the
      angiogenic cytokines VEGF, IL-8 and MCP-1 by RPE cells. Mitochondrial ROS was
      shown to play a role in the regulation of Abeta induced expression of these
      cytokines.

PMID- 28429669
TI  - What Can Pharmacological Models of Retinal Degeneration Tell Us?
AB  - Animal models with pharmacologically induced retinal degeneration including
      sodium iodate (NaIO3) and N-methyl-N-nitrosourea (MNU) have been extensively used
      in ophthalmic research to investigate retinal degeneration. NaIO3 induces
      degeneration of the retinal pigment epithelium (RPE) followed by photoreceptor
      (PRC) cell death, mimicking features of age-related macular degeneration. In
      contrast, MNU leads to rapid destruction of the PRCs only, enabling the use of
      the MNU model to investigate degeneration induced in retinitis pigmentosa. It has
      been shown that multiple cell death pathways are involved in the cell-specific
      effects of the toxins. Necrosis has been identified as the cause of the NaIO3
      induced RPE loss. PRC degeneration in the described models is mainly induced by
      programmed cell death, indicated by the upregulation of conventional apoptosis
      initiator and effector caspases. However, recent research points to the
      additional involvement of caspase-independent processes as endoplasmic reticulum
      stress and calpain activation. Since there is still a substantial amount of
      contradictory hypotheses concerning triggers of cell death, the use of
      pharmacological models is controversial. Thereby, the advantages of such models
      like the application reaching across species and strains as well as modulation of
      onset and severity of damage are not exploited to a full extent. Thus, the
      present review aims to give more insight into the involved cell death pathways
      and discusses recent findings in the most widely used retinal degeneration
      models. It might facilitate further studies aiming to develop putative
      therapeutic approaches for retinal degenerative diseases including combinatory
      treatment with cell death inhibitors and cell transplantation therapy.

PMID- 28429670
TI  - Expression of Dominant Negative K6W-Ubiquitin in the Lens Epithelium via an
      Adenoviral Vector Delays Posterior Capsule Opacification in a Rabbit Model.
AB  - PURPOSE: Ubiquitin is involved in cell proliferation and differentiation, and the
      objective of this study is to investigate the potential of dominant negative
      Ubiquitin (Ub) with a lysine to tryptophan mutation at the 6 position (K6W)
      through an adenoviral expression vector in the prevention of posterior capsule
      opacification (PCO) in a rabbit PCO model. METHODS: Recombinant dominant negative
      K6W-Ub adenovirus (RAd-K6W-Ub) with green fluorescent protein (RAd-K6W-Ub/GFP)
      and RAd-GFP viruses (control) were generated with QBI-HEK 293A cells. New Zealand
      rabbits receiving lens phacoemulsification were given an intraoperative anterior
      chamber injection of the viruses. The images of anterior segment photography
      taken by a slit lamp biomicroscopy were analyzed by posterior capsule
      opacification manual software (POCOman) for PCO grading. The intraocular pressure
      (IOP) was detected with a non-contact tonometer (NCT). The expression of alpha
      smooth muscle actin (alpha-SMA) was assessed by Western blotting. Cell migration
      ability in cultured rabbit's lens epithelial cells (LECs) was evaluated by
      scratch healing assay. RESULTS: The expression of GFP and Ub in the lens
      epithelium was markedly upregulated after 48 hours vector injection. Eyes
      injected with RAd-K6W-Ub showed a significantly lower PCO degree compared with
      controls. Meanwhile, higher IOP and corneal edema was observed in groups with a
      higher RAd-K6W-Ub virus dosage. The expression of alpha-SMA was down-regulated in
      the RAd-K6W-Ub eyes as compared to controls at the 15th day after injection. Cell
      migration was inhibited by RAd-K6W-Ub infection. CONCLUSIONS: RAd-K6W-Ub at an
      appropriate dosage could inhibit the proliferation of LECs and the formation of
      PCO in rabbit models. However, a higher dosage of Rad- K6W-Ub viral vector caused
      toxic effects to the surrounding tissues, such as corneal edema and high IOP.

PMID- 28429671
TI  - Ethanolamine Metabolism in the Mammalian Gastrointestinal Tract: Mechanisms,
      Patterns, and Importance.
AB  - Nutritional exchanges and cooperation between bacteria in the gastrointestinal
      tract and the mammalian host play an important role in health and disease.
      Ethanolamine is an essential dietary lipid nutrient for animals and is abundant
      in both intestinal and bacterial cell membranes. Ethanolamine can be utilized by
      intestinal eukaryotic cells via the cytidine phosphoethanolamine pathway for de
      novo synthesis of phosphatidylethanolamine, and certain bacteria are able to
      catabolize it as a major carbon and/or nitrogen source with the help of
      ethanolamine utilization proteins. In addition, ethanolamine utilization
      dramatically affects lipid metabolism and short-chain fatty acid biosynthesis.
      Ethanolamine metabolism plays a significant role in the renewal and proliferation
      of intestinal cells and intestinal inflammation, and ethanolamine may be a
      nutritional target to diagnose or treat diseases such as inflammatory bowel
      disease. This review summarizes the mechanisms of ethanolamine metabolism in the
      mammalian gastrointestinal tract and its influence on intestinal health and
      immunity, thus providing a theoretical reference for further studies on mammalian
      nutrition and disease.

PMID- 28429672
TI  - The Molecular Mechanisms of Thalidomide Teratogenicity and Implications for
      Modern Medicine.
AB  - Thalidomide is a teratogen that affects many organs but primarily induces limb
      truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s,
      this has led to misinterpretations of animal tests and to the fatal assumption
      that the drug was safe for pregnant women to use against morning sickness. The
      result was one of the biggest scandals in medical history: 10.000 and more
      infants with birth defects in Europe. Nonetheless, thalidomide still has its
      place in modern medicine as it has strong therapeutic potential: it has been
      approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its
      anti-inflammatory, immunomodulatory and antiangiogenic activities are considered
      in many other refractory diseases. The aim is to develop derivatives that are not
      teratogenic but maintain the therapeutic potential. This requires detailed
      knowledge about the underlying molecular mechanisms. Much progress has been made
      in deciphering the teratogenic mechanisms in the last decade. Here, we summarize
      these mechanisms, explain thalidomide resistance of rodents, and discuss possible
      mechanisms that could explain why the drug primarily targets the developing limb
      in the embryo. We also summarize the most important therapeutic mechanisms.
      Finally, we discuss which therapeutic and teratogenic mechanisms do and do not
      overlap, and if there is a chance for the development of non-teratogenic
      thalidomide derivatives with therapeutic potential.

PMID- 28429673
TI  - Hydroxytyrosol Attenuates LPS-Induced Acute Lung Injury in Mice by Regulating
      Autophagy and Sirtuin Expression.
AB  - BACKGROUND: Recently, the effects of hydroxytyrosol on autophagy during acute
      lung injury (ALI) have drawn increasing attention. OBJECTIVE: We explored the
      underlying molecular mechanisms by which hydroxytyrosol exerts its anti
      inflammatory effects in a murine model of ALI by up-regulating autophagy.
      METHODS: Male BALB/c mice, challenged with intranasal instillations of LPS, were
      treated with or without hydroxytyrosol (HT, 100 mg/kg, intragastrically) 1 h
      prior to LPS exposure. Twenty-four hours later, lung and bronchoalveolar lavage
      (BAL) fluid samples were obtained for the determination of lung wet to dry weight
      (W/D) ratios, protein leakage levels, and differential counts of inflammatory
      cells in BAL fluid. LPS-induced cytokine activity, inflammatory factor levels,
      sirtuin (SIRT1/3/6) expression, mitogenactivated protein kinase (MAPK)
      activation, and autophagy marker expression in ALImice were examined by western
      blotting and staining methods. Molecular docking between HT and SIRT and MAPK was
      studied with a Sybyl/Surflex module. RESULTS: LPS-stimulated SIRT inhibition,
      MAPK phosphorylation, and autophagy suppression were all notably abolished by HT
      administration. HT treatment significantly attenuated pulmonary edema and
      inflammatory cell infiltration into lung tissues, accompanied by decreased lung
      W/D ratios, protein concentrations, and inflammatory cell levels in BAL fluid.
      LPS driven release of inflammatory mediators, including TNF-alpha, IL-1beta, IL
      6, IL-10, and MCP-1, was strongly regulated by HT. CONCLUSIONS: The protective
      effect of HT on lung inflammation in ALI mice may be attributed to the promotion
      of autophagy, which is likely associated with the activation of the SIRT/MAPK
      signaling pathway. Importantly, this study provides new insight into the
      molecular mechanisms of HT and its therapeutic potential in the treatment of
      acute respiratory distress syndrome.

PMID- 28429674
TI  - Targeting the Role of Lipoprotein (a) in Stroke.
AB  - BACKGROUND: Stroke is the third leading cause of death in the United States,
      behind only heart disease and cancer, with over 140,000 associated deaths per
      year. METHODS: Considerable research is ongoing to examine the role of modifiable
      risk factors which may cause or contribute to stroke. Although age and family
      history are generally considered to be the major risk factors, there are several
      modifiable and non-modifiable risk factors that are linked to the pathogenesis of
      a stroke. Lipoprotein (a), or Lp(a), is a type of low-density lipoprotein
      containing an integral apolipoprotein B100 (apoB100) component with an attached
      apolipoprotein A-1 (ApoA-1) isoform via a disulfide linkage. Lp(a) metabolism is
      of great interest as it sheds light on its role in pathogenesis of not only
      cardiovascular disorders but also stroke. Although Lp(a) has been identified as
      an "LDL-like particle", its metabolism differs from low density lipoprotein
      (LDL). Despite some ambiguity in the literature regarding the causative effect of
      Lp(a) on stroke, there are clear associations of high plasma Lp(a) concentration
      and risk of stroke. Furthermore, the small isoforms of ApoA-1-containing
      lipoproteins have been shown to increase atherogenicity in atherosclerotic
      patients. CONCLUSION: Currently, there is little research examining the
      importance of small molecule Lp(a) distribution and risk for stroke, both on a
      first-case and recurrent basis. Understanding the role of Lp (a) in stroke
      requires investigating its molecular mechanisms particularly the key microRNA (s)
      components that control its expression and function (s). Therefore, the main
      objective of this review is to discuss the broader link between Lp(a) and stroke
      and to identify opportunities for future investigation and potential research
      prospects on the role of Lp (a) in stroke.

PMID- 28429675
TI  - Cell Biology of Hyphal Growth.
AB  - Filamentous fungi are a large and ancient clade of microorganisms that occupy a
      broad range of ecological niches. The success of filamentous fungi is largely due
      to their elongate hypha, a chain of cells, separated from each other by septa.
      Hyphae grow by polarized exocytosis at the apex, which allows the fungus to
      overcome long distances and invade many substrates, including soils and host
      tissues. Hyphal tip growth is initiated by establishment of a growth site and the
      subsequent maintenance of the growth axis, with transport of growth supplies,
      including membranes and proteins, delivered by motors along the cytoskeleton to
      the hyphal apex. Among the enzymes delivered are cell wall synthases that are
      exocytosed for local synthesis of the extracellular cell wall. Exocytosis is
      opposed by endocytic uptake of soluble and membrane-bound material into the cell.
      The first intracellular compartment in the endocytic pathway is the early
      endosomes, which emerge to perform essential additional functions as spatial
      organizers of the hyphal cell. Individual compartments within septated hyphae can
      communicate with each other via septal pores, which allow passage of cytoplasm or
      organelles to help differentiation within the mycelium. This article introduces
      the reader to more detailed aspects of hyphal growth in fungi.

PMID- 28429676
TI  - Determination of Dinotefuran and Its Metabolites in Orange Pulp, Orange Peel, and
      Whole Orange Using Liquid Chromatography-Tandem Mass Spectrometry.
AB  - Determination of the polar characteristics of dinotefuran and metabolite residues
      in orange matrixes (orange pulp, orange peel, and whole orange) is difficult.
      Thus, the purpose of the present study was to develop an extraction method for
      the determination of dinotefuran and its metabolites in oranges by using liquid
      chromatography with tandem mass spectrometry (LC-MS/MS). Matrix suppression
      effects were observed for all analytes in the orange matrixes. The proposed
      method displayed satisfactory linearity (R2 >= 0.9856) for the target molecules.
      The LODs were 0.03-0.10 mg/kg, whereas LOQs were 0.08-0.40 mg/kg for dinotefuran
      and its metabolites. Recoveries were 79.1-98.7% with RSD values <20% for all
      analytes in the orange matrixes. The proposed method was used to authenticate the
      samples and dinotefuran residues observed in field-incurred orange matrixes. The
      results of the proposed method could help the Chinese government establish
      maximum residue limits for dinotefuran in oranges and promote the safe and proper
      use of dinotefuran dosages in orange trees.

PMID- 28429677
TI  - Increased Expression of Cullin 3 in Nasopharyngeal Carcinoma and Knockdown
      Inhibits Proliferation and Invasion.
AB  - This study aimed to investigate the clinical significance of cullin 3 expression
      in nasopharyngeal carcinoma (NPC), as well as to explore the regulatory mechanism
      of cullin 3 underlying the growth and metastasis of NPC cells. Our findings
      showed that the expression levels of cullin 3 were significantly increased in
      both NPC tissues and cell lines. A strong positive correlation was found between
      cullin 3 expression and the Ki-67-based proliferation index in NPC tissues.
      Moreover, cullin 3 overexpression was correlated with local relapse and distant
      metastasis in NPC patients. In vitro experiments showed that knockdown of cullin
      3 caused a significant reduction in the proliferation of NPC cells, probably by
      inducing cell cycle arrest. In addition, downregulation of cullin 3 inhibited
      colony formation and the migratory and invasive capacities of NPC cells. The
      expression levels of PCNA and epithelial-to-mesenchymal transition (EMT)-related
      proteins were also meditated by cullin 3 in NPC cells. Based on these findings,
      we demonstrated that cullin 3 plays a promoting role in the malignant progression
      of NPC and suggest that the cullin 3-based ubiquitin proteasome pathway may be
      used as a promising therapeutic target for NPC.

PMID- 28429679
TI  - Mycobacterium avium Complex Disease.
AB  - Despite the ubiqitous nature of Mycobacterium avium complex (MAC) organisms in
      the environment, relatively few of those who are infected develop disease. Thus,
      some degree of susceptibility due to either underlying lung disease or
      immunosuppression is required. The frequency of pulmonary MAC disease is
      increasing in many areas, and the exact reasons are unknown. Isolation of MAC
      from a respiratory specimen does not necessarily mean that treatment is required,
      as the decision to treatment requires the synthesis of clinical, radiographic,
      and microbiologic information as well as a weighing of the risks and benefits for
      the individual patient. Successful treatment requires a multipronged approach
      that includes antibiotics, aggressive pulmonary hygiene, and sometimes resection
      of the diseased lung. A combination of azithromycin, rifampin, and ethambutol
      administered three times weekly is recommend for nodular bronchiectatic disease,
      whereas the same regimen may be used for cavitary disease but administered daily
      and often with inclusion of a parenteral aminoglycoside. Disseminated MAC (DMAC)
      is almost exclusively seen in patients with late-stage AIDS and can be treated
      with a macrolide in combination with ethambutol, with or without rifabutin: the
      most important intervention in this setting is to gain HIV control with the use
      of potent antiretroviral therapy. Treatment outcomes for many patients with MAC
      disease remain suboptimal, so new drugs and treatment regimens are greatly
      needed. Given the high rate of reinfection after cure, one of the greatest needs
      is a better understanding of where infection occurs and how this can be
      prevented.

PMID- 28429680
TI  - The Inhibitory Effects of HYDAMTIQ, a Novel PARP Inhibitor, on Growth in Human
      Tumor Cell Lines With Defective DNA Damage Response Pathways.
AB  - The poly(ADP-ribose) polymerase (PARP) enzymes play a key role in the regulation
      of cellular processes (e.g., DNA damage repair, genomic stability). It has been
      shown that PARP inhibitors (PARPIs) are selectively cytotoxic against cells
      having dysfunctions in genes involved in DNA repair mechanisms (synthetic
      lethality). Drug-induced PARP inhibition potentiates the activity of anticancer
      drugs such as 5-fluorouracil in enhancing DNA damage, whose repair involves PARP
      1 activity. The aim of this study was to evaluate the inhibitory effects of a
      novel PARPI, HYDAMTIQ, on growth in human tumor cell lines characterized by
      different features with regard to DNA damage response pathways (BRCA mutational
      status, microsatellite status, and ATM expression level) and degree of
      sensitivity/resistance to 5-fluorouracil. HYDAMTIQ showed a more potent
      inhibitory effect on cell growth in a BRCA2 mutant cell line (CAPAN-1) compared
      with wild-type cells (C2-6, C2-12, and C2-14 CAPAN-1 clones, and MCF-7). No
      statistically significant difference was observed after HYDAMTIQ exposure between
      cells having a different MS status or a different MRE11 mutational status.
      HYDAMTIQ induced greater antiproliferative effects in SW620 cells expressing a
      low level of ATM than in H630 cells expressing a high level of ATM. Finally, the
      combination of HYDAMTIQ and 5-fluorouracil exerted a synergistic effect on the
      inhibition of SW620 cell growth and an antagonistic effect on that of H630 cell
      growth. Our results show that the novel PARP inhibitor HYDAMTIQ potently inhibits
      the growth of human tumor cells with defective DNA damage response pathways and
      exerts synergistic cytotoxicity in combination with 5-fluorouracil. These data
      provide relevant examples of synthetic lethality and evidence for further
      development of this novel PARPI.

PMID- 28429681
TI  - Microwave diathermy in physiotherapy units: a survey on spatial and time
      heterogeneity of the electromagnetic field.
AB  - Microwave diathermy (MWD) is a therapeutic system that has been in use for some
      decades now in all physiotherapy settings, following the regulations of national
      facility establishments. The validity of diathermy devices is probably reduced as
      their working time increases, introducing the need for the device to be
      controlled/reset by qualified personnel in order to maintain its effectiveness in
      sessions and to accurately deliver the energy output that the physiotherapist
      asks for. However, while MWD has been a vital tool for practising
      physiotherapists, there is no clear evidence of a health burden due to incorrect
      usability. Additionally, due to the fact that physiotherapy rooms contain
      physiotherapeutic equipment it is observed that during the use of the diathermy
      device there is spatial heterogeneity in the interior space. In this work, the
      results are presented of the first national survey for quality control of MWD
      systems installed in physiotherapy rooms existing in urban and rural areas in
      Greece. Serious concerns about the technical status of the equipment as well as
      staff and patient safety, regarding the levels of non-ionising radiation emitted
      from MWD devices, are discussed. Additional evaluation is included of
      measurements in empty physiotherapy rooms while the MWD unit is transmitting at
      three different input powers (50 W/100 W/150 W-these are the therapeutic
      protocols used most frequently by physiotherapists) and in fully equipped
      physiotherapy rooms. Field strengths measured around MWDs normally working at
      different angles, distances and times compared to international limits revealed
      great spatial and time heterogeneity, raising serious concerns about the safety
      of occupational workers or other patients.

PMID- 28429682
TI  - Refractive index and extinction coefficient of NH2CH  =  NH2PbI3 perovskite
      photovoltaic material.
AB  - Very recently, the NH2CH  =  NH2PbI3 (FAPbI3) perovskite material has attracted
      considerable attention in fabricating solar cells (SCs). For a photovoltaic
      material, its refractive index and extinction coefficient, n(lambda) and
      k(lambda), as functions of lambda, are important to study its optical properties
      and to estimate the power conversion efficiency potential for the SCs made of it.
      As far as we know, to date there has been no reports of n(lambda) and k(lambda)
      for FAPbI3 material. In this article, with spectroscopic ellipsometry (SE)
      measurements, the n(lambda) and k(lambda), as well as E g  =  1.45 eV for FAPbI3,
      are acquired. The fast deposition crystallization (FDC) procedure combined with
      the slowed down annealing (SDA) process is applied to fabricate smooth and
      uniform FAPbI3 film on quartz substrate. Several kinds of organic solvents were
      tried as the second solvent in the FDC procedure, and it is found that when
      petroleum ether is used, the smallest surface roughness and good FAPbI3 material
      purity of the FAPbI3 film can be acquired. The k(lambda) results for FAPbI3
      obtained by SE, calculated from the n(lambda) using the Kramers-Kronig
      relationship, by absorbance, and by first-principles calculations, are compared.
      The n(lambda) and k(lambda) for FAPbI3 are also compared with those for
      CH3NH3PbI3, GaAs and c-Si.

PMID- 28429683
TI  - Biokinetics of yttrium and comparison with its geochemical twin holmium.
AB  - The transition metal yttrium (Y, atomic number 39) is chemically similar to
      elements in the lanthanide family (atomic numbers 57-71) and is found with the
      lanthanides in rare earth ores. Yttrium and the lanthanide holmium are referred
      to as geochemical twins because they generally show little fractionation from
      metamorphic or weathering processes, due to their closely similar chemical
      properties and nearly identical ionic radii. Extensive measurements on rocks,
      soils, and meteorites indicate that the Y/Ho mass concentration ratio rarely
      falls far from the so-called chondritic or solar system ratio of ~26. This paper
      presents a new biokinetic model for yttrium in adult humans and examines whether
      yttrium and holmium may be biological as well as geochemical twins, considering
      model-based comparisons of their systemic behaviours in adult humans and model
      free comparisons of their concentration ratios in human tissues and various types
      of vegetation. It appears that yttrium and holmium behave similarly in the human
      body and that their concentration ratios tend to cluster near the chondritic
      value in human tissues as well as plants, but the comparative information is too
      limited and imprecise to determine whether they are extremely close biological
      analogues.

PMID- 28429684
TI  - Enhanced photocathodic protection performance of Ag/graphene/TiO2 composite for
      304SS under visible light.
AB  - Ag and graphene co-sensitized TiO2 composites were successfully fabricated and
      used as photoanodes for photogenerated cathodic protection of 304 stainless steel
      (304SS) under visible light. Graphene films was firstly deposited onto the TiO2
      nanotube (NT) films via cyclic voltammetric electrodeposition. Ag/graphene/TiO2
      films were then fabricated via dipping and photoreduction method. The morphology,
      composition and optical response of the Ag/graphene/TiO2 NT composites were
      characterized by scanning electron microscopy, x-ray diffraction, x-ray
      photoelectron spectroscopy, UV-vis diffusion reflectance spectroscopy,
      respectively. The photocathodic protection performance of the Ag/graphene/TiO2
      composites were systematically studied through open-circuit potential and
      potentiodynamic polarization measurements in 3.5 wt% NaCl solution under visible
      light (lambda > 400 nm). The composites exhibited enhanced photogenerated
      cathodic protection performance for 304SS under visible light irradiation
      compared to pure TiO2. Graphene and Ag have a synergistic effect on the
      enhancement of photocathodic protection performance of TiO2. The composites
      prepared with 30-cycle graphene film and 15 mM AgNO3 solution showed the optimal
      corrosion protection performance.

PMID- 28429685
TI  - Interlayer-crosslinked micelles prepared from star-shaped copolymers via click
      chemistry for sustained drug release.
AB  - To balance the stability and the particle size of polymeric micelles, star-shaped
      copolymers Hx-yne-N3-PEG containing both alkynyl and azido groups were
      synthesized from hyperbranched 2,2-bismethylolpropionic acid polyester (H20 with
      16 hydroxyl, H30 with 32 hydroxyl, H40 with 64 hydroxyl) to develop interlayer
      crosslinked micelles by click chemistry. The results of dynamic light scattering
      indicate that the crosslinking could enhance the stability of polymeric micelles.
      The crosslinked micelles are regular nanosized (approximately 20 nm) spheres
      observed by a transmission electron microscope. The crosslinked micelles have
      better drug loading capacity and more sustained drug release behavior than the un
      crosslinked micelles.

PMID- 28429686
TI  - [Is lower better? Is lowest the best?]

PMID- 28429687
TI  - Postural orthostatic tachycardia: A syndrome requiring detailed search for
      associated conditions.

PMID- 28429688
TI  - Anemia and heart failure: Is there still a role for erythropoiesis-stimulating
      agents?

PMID- 28429689
TI  - Relationship between fragmented QRS complexes in leads V4-V6 and left ventricular
      apical thrombus formation in patients presenting with first acute anterior
      myocardial infarction.
AB  - OBJECTIVE: The present study was an investigation of the relationship between
      fragmented QRS (fQRS) and left ventricular apical thrombus (LVAT) in patients
      presenting with first acute anterior myocardial infarction (MI). METHODS:
      Consecutive 148 patients (mean age: 60.1+/-10.1 years; male: 75.6%) with first
      acute anterior MI who underwent primary percutaneous coronary intervention (PCI)
      were included. Study population was divided into 2 groups based on presence of
      LVAT. fQRS was defined as presence of various RSR' patterns, which included
      additional R wave or notching of R wave or S wave, and presence of more than 1 R
      in 2 contiguous leads corresponding to major coronary artery territory on 12-lead
      electrocardiogram. Patients with bundle branch block were excluded from the
      study. RESULTS: Of these, 32 (21.6%) had LVAT. Patients with LVAT had higher
      prevalence of fQRS (53.1% vs. 22.4%; p<0.001) and lower rate of successful PCI
      (75% vs. 94%; p=0.002) compared with patients without LVAT. More patients in LVAT
      group had left ventricular ejection fraction of <30% (87.5% vs 65.5%; p=0.010).
      Groups were similar with respect to other baseline characteristics (p>0.05 for
      all). Presence of fQRS was independent predictor of LVAT (odds ratio [OR], 2.795;
      95% confidence interval [CI], 1.058-7.396) in multivariable logistic regression
      analysis. CONCLUSION: Presence of fQRS in leads V4-V6 is independently associated
      with LVAT in patients presenting with first acute anterior MI.

PMID- 28429690
TI  - [Our experience in the diagnosis and treatment of postural orthostatic
      tachycardia syndrome, vasovagal syncope, and inappropriate sinus tachycardia in
      children].
AB  - OBJECTIVES: The aim of this study was to share our experience in the diagnosis
      and treatment of patients who presented at our clinic with syncope, pre-syncope,
      dizziness, and palpitations. STUDY DESIGN: Patients who were treated at pediatric
      cardiology clinic for complaints of syncope, dizziness, and palpitations between
      2014 and 2016 were enrolled in the study. Detailed history of the patients,
      physical examination findings, laboratory and electrocardiogram results were
      recorded. Tilt table test, 24-hour Holter rhythm monitoring, and exercise test
      were performed, as required. Patients were diagnosed as vasovagal syncope,
      postural orthostatic tachycardia syndrome (POTS), or inappropriate sinus
      tachycardia based on these findings. Treatment of the patients was evaluated.
      RESULTS: Thirty patients were diagnosed as vasovagal syncope, 7 patients as POTS,
      and 2 as inappropriate sinus tachycardia. POTS accompanied Raynaud's phenomenon
      in 1 patient, hypertrophic cardiomyopathy in 1 patient, and homocystinuria in
      another patient. Complaints of patients with vasovagal syncope improved with non
      medical therapy. Medical treatment was administered to the patients with
      diagnosis of POTS and inappropriate sinus tachycardia. CONCLUSION: In patients
      with complaints of syncope, pre-syncope, dizziness, and palpitations without
      structural heart disease or non-rhythm problems, cardiovascular autonomic
      disorders, such as POTS and inappropriate sinus tachycardia should be kept in
      mind, as well as vasovagal syncope.

PMID- 28429691
TI  - Comparison of the effects of high-dose atorvastatin and high-dose rosuvastatin on
      oxidative stress in patients with acute myocardial infarction: A pilot study.
AB  - OBJECTIVE: Oxidative stress is increased in patients with acute myocardial
      infarction (AMI). Statins reduce oxidative stress independent of their effect in
      reducing low-density lipoprotein cholesterol (LDL-C). The aim of the present
      study was to compare the effects of atorvastatin and rosuvastatin on oxidative
      status by investigating serum paraoxonase, serum arylesterase, total oxidant
      status, total antioxidant status (TAS) and oxidative stress index (OSI) in
      patients with AMI. METHODS: Seventy patients with AMI were randomized into 2
      groups; total of 55 patients (19 females, 36 males) aged 32 to 86 years completed
      the study and were included in the analysis. Patients were treated with 80 mg
      atorvastatin or 40 mg rosuvastatin for 4 weeks. Lipid parameters and parameters
      of oxidative status were measured at admission and after 4-week statin treatment.
      RESULTS: After 4-week treatment, atorvastatin and rosuvastatin were associated
      with significant reduction in TAS, OSI, total cholesterol, and LDL-C levels.
      Serum paraoxonase level was significantly increased in both groups, while high
      density lipoprotein cholesterol (HDL-C) level was significantly reduced in
      atorvastatin group. No statistically significant differences were found between
      atorvastatin and rosuvastatin in terms of actual difference in oxidative stress
      parameters. CONCLUSION: Atorvastatin and rosuvastatin have similar effects on
      oxidative status in patients with AMI. Rosuvastatin affected HDL-C level more
      favorably than atorvastatin.

PMID- 28429692
TI  - Pulmonary artery and right ventricle function in patients with bicuspid aortic
      valve.
AB  - OBJECTIVE: Bicuspid aortic valve (BAV) is a complex developmental anomaly caused
      by abnormal aortic leaflet formation during valvulogenesis. The present study is
      an assessment of the effects of BAV disease on the ascending aorta and pulmonary
      artery (PA), and an evaluation of the consequences for systolic and diastolic
      functioning of the left and right ventricles. METHODS: Total of 66 patients were
      eligible for inclusion. Pulmonary artery maximum diameter (PAD) was obtained 1 cm
      distal to the pulmonary annulus. Using pulsed-wave tissue Doppler imaging, left
      ventricular (LV) early diastolic velocity (E') measurement was obtained at the
      annulus with placement of sample volume. Right ventricle (RV) peak global strain
      rate during systole (RV-SRS), early diastole (RV-SRE), and late diastole (RV-SRA)
      were calculated. RESULTS: In this study, 40.9% (n=27) of patients were female and
      average age was 35+/-11years. RV-SRS values (beta=-.781, t=-2.723; p=0.010) and
      log-LV tissue Doppler imaging E' (beta=-2.996, t=-5.405; p=<0.001) were
      negatively correlated, and log-PAD (beta=4.861, t=3.052; p=0.005) was positively
      and independently correlated with ascending aortic diameter. CONCLUSION:
      Ascending aorta diameter is positively correlated with PA diameter in BAV
      patients, and RV strain rate and LV diastolic parameters are affected before
      development of the valve disease.

PMID- 28429693
TI  - Predictors of neurologically favorable survival among patients with out-of
      hospital cardiac arrest: A tertiary referral hospital experience.
AB  - OBJECTIVE: Despite recent advances in medical support and interventions, only 5%
      to 10% of patients with out-of-hospital cardiac arrest (OHCA) survive to
      discharge. In this study, factors related to neurologically favorable survival in
      patients with OHCA were analyzed. METHODS: A total of 129 patients who were
      admitted to hospital with OHCA were retrospectively enrolled. RESULTS: Sustained
      return of spontaneous circulation (ROSC) (ROSC lasting >20 min) was achieved in
      29 (22.4%) patients. Percentage of cardiac arrests with ischemic etiology was
      significantly higher in successful ROSC group (p<0.001). In multivariate logistic
      regression analysis, cardiac arrest with ischemic etiology (p=0.004) and
      cardiopulmonary resuscitation (CPR) duration (p=0.013) were found to be
      independent predictors for ROSC. One-minute increment in CPR duration was
      associated with 1.202-fold increase in failure to achieve ROSC. Among patients
      with ROSC, 7 (5.4%) survived to hospital discharge, and 1-minute increment in CPR
      duration was associated with a 1.123-fold decrease in neurologically favorable
      survival (p=0.005). CONCLUSION: In patients with OHCA, ischemic etiology is
      associated with better ROSC rate compared to other reasons for cardiac arrest,
      and patients with prolonged CPR are less likely to survive.

PMID- 28429694
TI  - The rationale and design of the national familial hypercholesterolemia registries
      in Turkey: A-HIT1 and A-HIT2 studies.
AB  - OBJECTIVE: Familial hypercholesterolemia (FH) is a genetic disease characterized
      by extremely high levels of cholesterol, leading to premature atherosclerosis.
      Although many countries have already addressed the burden of FH by means of
      national registries, Turkey has no national FH registry or national screening
      program to detect FH. Creation of a series of FH registries is planned as part of
      Turkish FH Initiative endorsed by the Turkish Society of Cardiology to meet this
      need. This article provides detailed information on the rationale and design of
      the first 2 FH registries (A-HIT1 and A-HIT2). METHODS: A-HIT1 is a nationwide
      survey of adult homozygous FH (HoFH) patients undergoing low-density lipoprotein
      (LDL) apheresis (LA) in Turkey. A-HIT1 will provide insight into the clinical
      status of HoFH patients undergoing LA. Primary objective of this cross-sectional
      study is to identify how HoFH patients on LA are managed. Inclusion criteria are
      age >12 years, diagnosis of HoFH, and regular LA treatment. All available
      apheresis centers were electronically invited to participate in the study. The
      principal physicians of each center will respond to a questionnaire regarding
      their attitude toward LA. For each patient, another questionnaire will be used to
      collect data on clinical status, medication use, and disease data. In addition,
      patients will be asked to complete self-report questionnaires that provide
      information on quality of life, disease-related anxiety, and depression. A-HIT2
      is a registry of adult FH patients presenting at outpatient clinics. At least
      1000 FH patients will be recruited from 30 outpatient clinics representing the 12
      statistical regions in Turkey based on the EU NUTS classification. Sites
      specializing in cardiology, internal medicine, and endocrinology were invited to
      participate. The primary objective of this cross-sectional study is to determine
      clinical status and management of patients in Turkey diagnosed with FH.
      Eligibility for screening was defined as having LDL-cholesterol level >160 mg/dL.
      Inclusion criteria are age >18 years and diagnosis as possible FH (total score of
      >2 according to Dutch Lipid Clinic Network criteria). In addition to measuring
      clinical status of patients, a short survey to assess patient level of disease
      awareness will also be administered. CONCLUSION: A-HIT1 and A-HIT2 are the first
      nationwide FH registries in Turkey and will provide important information on the
      management of Turkish FH patients. In addition, it is planned that they will
      guide establishment of a national policy for the diagnosis and treatment of FH in
      Turkey.

PMID- 28429695
TI  - Lichenoid type cutaneous hyperpigmentation induced by nebivolol.
AB  - Cutaneous hyperpigmentation is a common and well-defined side effect of many
      drugs, such as non-steroidal anti-inflammatory drugs, beta-blockers, and
      tetracyclines, but to the best of our knowledge there is no case of skin
      discoloration related to nebivolol in the literature. Presently described is
      lichenoid type cutaneous hyperpigmentation in a 46-year-old female patient.
      Hyperpigmentation emerged 3 months after initiating use of nebivolol and resolved
      after cessation of drug use. It was concluded that effect emerged as result of
      therapeutic doses of nebivolol.

PMID- 28429696
TI  - Polymorphic ventricular tachycardia due to variant angina diagnosed on Holter
      monitoring and confirmed with cold pressor test.
AB  - A 52-year-old man complaining of persistent recurring chest pain at night
      underwent coronary angiogram at another institution. Normal coronaries were
      observed and he was discharged with muscle spasmolytic prescription. Since
      symptoms had continued, 24-hour Holter monitoring was ordered at our facility and
      results revealed huge ST elevation and polymorphic ventricular tachycardia. Cold
      pressor test performed in catheterization laboratory also resulted in ventricular
      tachycardia. Nifedipine was prescribed and follow-up Holter monitoring revealed
      no further vasospastic episodes. Utility of 24-hour Holter rhythm monitoring and
      cold pressor test in patients with recurrent chest pain at night is demonstrated
      in this report.

PMID- 28429697
TI  - [Reversible first-degree atrioventricular block due to hyperthyroidism].
AB  - Hyperthyroidism often causes tachyarrhythmia. Reversible atrioventricular block
      caused by hyperthyroidism is rare occurrence. Presently described is a case of
      atrioventricular block due to hyperthyroidism and recovery after antithyroid
      treatment.

PMID- 28429698
TI  - Coronary microvascular dysfunction equivalent to left main coronary artery
      disease.
AB  - Coronary microvascular dysfunction, also known as cardiac syndrome X, is a
      clinical syndrome presenting with typical angina and evidence of myocardial
      ischemia in the absence of flow-limiting stenosis on coronary angiography. Of
      patients undergoing coronary angiography due to suspected myocardial ischemia,
      50% are found to have normal or near-normal coronary arteries. Described in this
      case report is a patient who developed hypotension and ST segment depressions
      during treadmill exercise test. Left main coronary artery or multivessel disease
      was suspected. Coronary angiography was normal, but coronary flow reserve
      measurement revealed severe microvascular dysfunction.

PMID- 28429699
TI  - Quantitative assessment of the effect of subclavian steal syndrome on left
      anterior descending artery flow.
AB  - We presented a case of subclavian steal syndrome which has been evaluated and
      treated quantitatively by using fractional flow reserve technique. Treatment
      strategy to resolve symptoms of angina in patients with steal syndrome is
      controversial. Quantitative evaluation should direct choice of treatment
      strategy.

PMID- 28429700
TI  - Acute lower extremity paralysis after lower extremity endovascular intervention.
AB  - A 61-year-old man underwent successful percutaneous revascularization of both
      lower limbs with multiple stent implantations. Paralysis of right lower limb was
      noticed after completion of procedure when transferring the patient from
      angiography table. Since hematoma compressing lumbosacral neural plexus could be
      a fatal complication, computed tomography (CT) image was taken. CT showed bulge
      of distended bladder compressing stent struts. Following placement of Foley
      catheter, condition improved and he was subsequently discharged uneventfully.

PMID- 28429701
TI  - [Microbiota and metabolic syndrome].
AB  - The role of gut bacteria in the pathogenesis and treatment of various diseases
      has been a focus of attention in the last 10 years. Prevalence of diabetes,
      obesity, and cardiovascular diseases continues to increase, in spite of
      technological developments and treatment alternatives. Microbial dysbiosis,
      described as the decrease of useful bacteria and the increase of harmful
      bacteria, has been associated with diabetes, obesity, atherosclerosis, and
      metabolic syndrome. In microbial dysbiosis, increase of harmful metabolites and
      changes to composition of bile acids occur via carbohydrate and protein
      fermentation. As a result, insulin resistance pathways are activated, which
      initiate the processes of obesity, diabetes, and atherosclerosis. Healthy diet
      recommendations, including prebiotic and probiotic foods and the use of probiotic
      agents, look promising for future treatment of metabolic syndrome and
      cardiovascular diseases.

PMID- 28429702
TI  - Case Images: Successful ablation of paroxysmal atrial fibrillation originating in
      left atrial appendage with single shot cryoballoon technique.

PMID- 28429703
TI  - Case Images: Multimodality imaging in a patient with lead perforation.

PMID- 28429704
TI  - Case Images: Huge multicavitated left atrial mass mimicking mitral stenosis.

PMID- 28429705
TI  - Case Images: A severe aortic coarctation newly diagnosed during cardiac
      catheterization in an adult presenting with acute anterior myocardial infarction.

PMID- 28429706
TI  - Direct comparison of distinct naive pluripotent states in human embryonic stem
      cells.
AB  - Until recently, human embryonic stem cells (hESCs) were shown to exist in a state
      of primed pluripotency, while mouse embryonic stem cells (mESCs) display a naive
      or primed pluripotent state. Here we show the rapid conversion of in-house
      derived primed hESCs on mouse embryonic feeder layer (MEF) to a naive state
      within 5-6 days in naive conversion media (NCM-MEF), 6-10 days in naive human
      stem cell media (NHSM-MEF) and 14-20 days using the reverse-toggle protocol (RT
      MEF). We further observe enhanced unbiased lineage-specific differentiation
      potential of naive hESCs converted in NCM-MEF, however, all naive hESCs fail to
      differentiate towards functional cell types. RNA-seq analysis reveals a divergent
      role of PI3K/AKT/mTORC signalling, specifically of the mTORC2 subunit, in the
      different naive hESCs. Overall, we demonstrate a direct evaluation of several
      naive culture conditions performed in the same laboratory, thereby contributing
      to an unbiased, more in-depth understanding of different naive hESCs.

PMID- 28429707
TI  - The human amygdala parametrically encodes the intensity of specific facial
      emotions and their categorical ambiguity.
AB  - The human amygdala is a key structure for processing emotional facial
      expressions, but it remains unclear what aspects of emotion are processed. We
      investigated this question with three different approaches: behavioural analysis
      of 3 amygdala lesion patients, neuroimaging of 19 healthy adults, and single
      neuron recordings in 9 neurosurgical patients. The lesion patients showed a shift
      in behavioural sensitivity to fear, and amygdala BOLD responses were modulated by
      both fear and emotion ambiguity (the uncertainty that a facial expression is
      categorized as fearful or happy). We found two populations of neurons, one whose
      response correlated with increasing degree of fear, or happiness, and a second
      whose response primarily decreased as a linear function of emotion ambiguity.
      Together, our results indicate that the human amygdala processes both the degree
      of emotion in facial expressions and the categorical ambiguity of the emotion
      shown and that these two aspects of amygdala processing can be most clearly
      distinguished at the level of single neurons.

PMID- 28429708
TI  - Bi1Te1 is a dual topological insulator.
AB  - New three-dimensional (3D) topological phases can emerge in superlattices
      containing constituents of known two-dimensional topologies. Here we demonstrate
      that stoichiometric Bi1Te1, which is a natural superlattice of alternating two
      Bi2Te3 quintuple layers and one Bi bilayer, is a dual 3D topological insulator
      where a weak topological insulator phase and topological crystalline insulator
      phase appear simultaneously. By density functional theory, we find indices
      (0;001) and a non-zero mirror Chern number. We have synthesized Bi1Te1 by
      molecular beam epitaxy and found evidence for its topological crystalline and
      weak topological character by spin- and angle-resolved photoemission
      spectroscopy. The dual topology opens the possibility to gap the differently
      protected metallic surface states on different surfaces independently by breaking
      the respective symmetries, for example, by magnetic field on one surface and by
      strain on another surface.

PMID- 28429709
TI  - T follicular helper and T follicular regulatory cells have different TCR
      specificity.
AB  - Immunization leads to the formation of germinal centres (GCs) that contain both T
      follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell
      receptor (TCR) specificity defines the differential functions of Tfh and Tfr
      cells is unclear. Here we show that antigen-specific T cells after immunization
      are preferentially recruited to the GC to become Tfh cells, but not Tfr cells.
      Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with
      the same immunizing antigen in vitro. Ex vivo TCR repertoire analysis shows that
      immunization induces oligoclonal expansion of Tfh cells. By contrast, the Tfr
      pool has a TCR repertoire that more closely resembles that of regulatory T (Treg)
      cells. Our data thus indicate that the GC Tfh and Tfr pools are generated from
      distinct TCR repertoires, with Tfh cells expressing antigen-responsive TCRs to
      promote antibody responses, and Tfr cells expressing potentially autoreactive
      TCRs to suppress autoimmunity.

PMID- 28429710
TI  - Life cycle assessment needs predictive spatial modelling for biodiversity and
      ecosystem services.
AB  - International corporations in an increasingly globalized economy exert a major
      influence on the planet's land use and resources through their product design and
      material sourcing decisions. Many companies use life cycle assessment (LCA) to
      evaluate their sustainability, yet commonly-used LCA methodologies lack the
      spatial resolution and predictive ecological information to reveal key impacts on
      climate, water and biodiversity. We present advances for LCA that integrate
      spatially explicit modelling of land change and ecosystem services in a Land-Use
      Change Improved (LUCI)-LCA. Comparing increased demand for bioplastics derived
      from two alternative feedstock-location scenarios for maize and sugarcane, we
      find that the LUCI-LCA approach yields results opposite to those of standard LCA
      for greenhouse gas emissions and water consumption, and of different magnitudes
      for soil erosion and biodiversity. This approach highlights the importance of
      including information about where and how land-use change and related impacts
      will occur in supply chain and innovation decisions.

PMID- 28429711
TI  - Single-photon test of hyper-complex quantum theories using a metamaterial.
AB  - In standard quantum mechanics, complex numbers are used to describe the
      wavefunction. Although this has so far proven sufficient to predict experimental
      results, there is no theoretical reason to choose them over real numbers or
      generalizations of complex numbers, that is, hyper-complex numbers. Experiments
      performed to date have proven that real numbers are insufficient, but the need
      for hyper-complex numbers remains an open question. Here we experimentally probe
      hyper-complex quantum theories, studying one of their deviations from complex
      quantum theory: the non-commutativity of phases. We do so by passing single
      photons through a Sagnac interferometer containing both a metamaterial with a
      negative refractive index, and a positive phase shifter. To accomplish this we
      engineered a fishnet metamaterial to have a negative refractive index at 780 nm.
      We show that the metamaterial phase commutes with other phases with high
      precision, allowing us to place limits on a particular prediction of hyper
      complex quantum theories.

PMID- 28429712
TI  - Electron transport and visible light absorption in a plasmonic photocatalyst
      based on strontium niobate.
AB  - Semiconductor compounds are widely used for photocatalytic hydrogen production
      applications, where photogenerated electron-hole pairs are exploited to induce
      catalysis. Recently, powders of a metallic oxide (Sr1-xNbO3, 0.03<x<0.20) were
      reported to show competitive photocatalytic efficiencies under visible light,
      which was attributed to interband absorption. This discovery expanded the range
      of materials available for optimized performance as photocatalysts. Here we study
      epitaxial thin films of SrNbO3+delta and find that their bandgaps are ~4.1 eV.
      Surprisingly, the carrier density of the conducting phase exceeds 1022 cm-3 and
      the carrier mobility is only 2.47 cm2 V-1 s-1. Contrary to earlier reports, the
      visible light absorption at 1.8 eV (~688 nm) is due to the plasmon resonance,
      arising from the large carrier density. We propose that the hot electron and hole
      carriers excited via Landau damping (during the plasmon decay) are responsible
      for the photocatalytic property of this material under visible light irradiation.

PMID- 28429713
TI  - Gating of TonB-dependent transporters by substrate-specific forced remodelling.
AB  - Membrane proteins play vital roles in inside-out and outside-in signal
      transduction by responding to inputs that include mechanical stimuli. Mechanical
      gating may be mediated by the membrane or by protein(s) but evidence for the
      latter is scarce. Here we use force spectroscopy, protein engineering and
      bacterial growth assays to investigate the effects of force on complexes formed
      between TonB and TonB-dependent transporters (TBDT) from Gram-negative bacteria.
      We confirm the feasibility of protein-only mediated mechanical gating by
      demonstrating that the interaction between TonB and BtuB (a TBDT) is sufficiently
      strong under force to create a channel through the TBDT. In addition, by
      comparing the dimensions of the force-induced channel in BtuB and a second TBDT
      (FhuA), we show that the mechanical properties of the interaction are perfectly
      tuned to their function by inducing formation of a channel whose dimensions are
      tailored to the ligand.

PMID- 28429715
TI  - Mapping clinicopathological entities within colorectal mucinous adenocarcinomas:
      a hierarchical clustering approach.
AB  - The aim of this study was to interrogate the heterogeneity of colorectal mucinous
      adenocarcinomas. This study is based on hierarchical clustering approach
      combining clinicopathological and molecular patterns known to be relevant to
      oncogenesis and therapeutic management of patients with colorectal carcinoma, ie,
      microsatellite instability, O6-methylguanine-DNA methyltransferase (MGMT) status,
      KRAS, and BRAF mutations and wnt signaling pathway activation. Comparison of the
      study group of 60 mucinous adenocarcinomas defined according to World Health
      Organization classification with control group of 136 colorectal adenocarcinomas
      successively removed shows higher frequency of BRAF and KRAS mutations and
      microsatellite instability-high status and lower frequency of wnt signaling
      pathway activation in mucinous adenocarcinomas. Hierarchical clustering isolated
      three relevant clusters: (i) cluster of microsatellite stable mucinous
      adenocarcinomas (54%) with KRAS mutation, and frequent MGMT changes, more
      frequently located in the left colon, often associated with contiguous precursor
      adenoma; (ii) cluster of BRAF-mutated mucinous adenocarcinomas (28%) with either
      microsatellite instability-high or microsatellite stable status, occurring in
      elderly female patients, nearly all located in the right colon, having the
      signature of serrated pathway of carcinomas; and (iii) a heterogeneous cluster of
      microsatellite instability-high mucinous carcinomas (18%), including inherited
      colorectal carcinomas, displaying a high-grade histological pattern. Age, TNM
      stage, and BRAF mutation had prognostic value. Hierarchical clustering analysis
      led to the identification of several clinicopathological entities of colorectal
      mucinous adenocarcinomas with epidemiologic, prognostic, and therapy relevance.
      Both KRAS and BRAF mutations appear as drivers in the alternate oncogenetic
      pathways governing the development of sporadic colorectal mucinous
      adenocarcinomas.

PMID- 28429714
TI  - PIF1 family DNA helicases suppress R-loop mediated genome instability at tRNA
      genes.
AB  - Saccharomyces cerevisiae encodes two Pif1 family DNA helicases, Pif1 and Rrm3.
      Rrm3 promotes DNA replication past stable protein complexes at tRNA genes
      (tDNAs). We identify a new role for the Pif1 helicase: promotion of replication
      and suppression of DNA damage at tDNAs. Pif1 binds multiple tDNAs, and this
      binding is higher in rrm3Delta cells. Accumulation of replication intermediates
      and DNA damage at tDNAs is higher in pif1Delta rrm3Delta than in rrm3Delta cells.
      DNA damage at tDNAs in the absence of these helicases is suppressed by
      destabilizing R-loops while Pif1 and Rrm3 binding to tDNAs is increased upon R
      loop stabilization. We propose that Rrm3 and Pif1 promote genome stability at
      tDNAs by displacing the stable multi-protein transcription complex and by
      removing R-loops. Thus, we identify tDNAs as a new source of R-loop-mediated DNA
      damage. Given their large number and high transcription rate, tDNAs may be a
      potent source of genome instability.

PMID- 28429716
TI  - Polyembryoma of the testis: a report of two cases dominant within mixed germ cell
      tumors and review of gonadal polyembryomas.
AB  - Two testicular mixed germ cell tumors, from men of 21 and 41 years, in which
      polyembryoma predominated are described. A literature review uncovered an
      additional five testicular and nine ovarian cases. One tumor occurred in a 60
      year-old man, but all others occurred within the typical age range of gonadal
      germ cell tumors. One male presented with gynecomastia and one female with sexual
      precocity, but all otherwise had standard clinical manifestations. These tumors
      are typically large with non-specific gross features, but a few have a prominent
      hemorrhagic appearance. No tumor is known to have been entirely composed of
      embryoid bodies, the unit upon which the diagnosis of polyembryoma is based. The
      most common additional germ cell tumor component is teratoma, present in the
      great majority of cases, with an approximately equal smaller number of tumors
      being associated with embryonal carcinoma and yolk-sac tumor, manifest as
      overgrowths of these elements, derived from the parent epithelium within the
      embryoid body. Rarely there is choriocarcinoma, and syncytiotrophoblast and
      hepatoid cells are occasionally present. The microscopic features of the tumors
      vary according to the arrangement of embryoid bodies with other elements, the
      prominence of associated typically myxoid to edematous stroma, and the degree to
      which embryoid bodies are perfectly or imperfectly formed. Although its presence
      in a gonadal mixed germ cell tumor is probably not associated with any special
      behavior, its unique features should result in polyembryoma being recorded,
      particularly when present in significant amount. Furthermore, awareness of its
      features may facilitate recognition, particularly when seen at metastatic sites
      or extra-gonadal sites of primary germ cell neoplasia. Whether polyembroma should
      be considered a distinctive pattern of mixed germ cell neoplasia or a particular
      variant of high-grade immature teratoma is considered, herein, and arguments can
      be made in favor of each viewpoint.

PMID- 28429717
TI  - Exploratory adaptation in large random networks.
AB  - The capacity of cells and organisms to respond to challenging conditions in a
      repeatable manner is limited by a finite repertoire of pre-evolved adaptive
      responses. Beyond this capacity, cells can use exploratory dynamics to cope with
      a much broader array of conditions. However, the process of adaptation by
      exploratory dynamics within the lifetime of a cell is not well understood. Here
      we demonstrate the feasibility of exploratory adaptation in a high-dimensional
      network model of gene regulation. Exploration is initiated by failure to comply
      with a constraint and is implemented by random sampling of network
      configurations. It ceases if and when the network reaches a stable state
      satisfying the constraint. We find that successful convergence (adaptation) in
      high dimensions requires outgoing network hubs and is enhanced by their auto
      regulation. The ability of these empirically validated features of gene
      regulatory networks to support exploratory adaptation without fine-tuning, makes
      it plausible for biological implementation.

PMID- 28429718
TI  - A computational systems approach identifies synergistic specification genes that
      facilitate lineage conversion to prostate tissue.
AB  - To date, reprogramming strategies for generating cell types of interest have been
      facilitated by detailed understanding of relevant developmental regulatory
      factors. However, identification of such regulatory drivers often represents a
      major challenge, as specific gene combinations may be required for reprogramming.
      Here we show that a computational systems approach can identify cell type
      specification genes (master regulators) that act synergistically, and demonstrate
      its application for reprogramming of fibroblasts to prostate tissue. We use three
      such master regulators (FOXA1, NKX3.1 and androgen receptor, AR) in a primed
      conversion strategy starting from mouse fibroblasts, resulting in prostate tissue
      grafts with appropriate histological and molecular properties that respond to
      androgen-deprivation. Moreover, generation of reprogrammed prostate does not
      require traversal of a pluripotent state. Thus, we describe a general strategy by
      which cell types and tissues can be generated even with limited knowledge of the
      developmental pathways required for their specification in vivo.

PMID- 28429719
TI  - Transiently antigen-primed B cells return to naive-like state in absence of T
      cell help.
AB  - The perspective that naive B-cell recognition of antigen in the absence of T-cell
      help causes cell death or anergy is supported by in vivo studies of B cells that
      are continuously exposed to self-antigens. However, intravital imaging suggests
      that early B-cell recognition of large foreign antigens may be transient. Whether
      B cells are tolerized or can be recruited into humoural immune responses
      following such encounters is not clear. Here we show that in the presence of T
      cell help, single transient antigen acquisition is sufficient to recruit B cells
      into the germinal centre and induce memory and plasma cell responses. In the
      absence of T-cell help, transiently antigen-primed B cells do not undergo
      apoptosis in vivo; they return to quiescence and are recruited efficiently into
      humoural responses upon reacquisition of antigen and T-cell help.

PMID- 28429723
TI  - Pressure Self-focusing Effect and Novel Methods for Increasing the Maximum
      Pressure in Traditional and Rotational Diamond Anvil Cells.
AB  - The main principles of producing a region near the center of a sample, compressed
      in a diamond anvil cell (DAC), with a very high pressure gradient and,
      consequently, with high pressure are predicted theoretically. The revealed
      phenomenon of generating extremely high pressure gradient is called the pressure
      self-focusing effect. Initial analytical predictions utilized generalization of a
      simplified equilibrium equation. Then, the results are refined using our recent
      advanced model for elastoplastic material under high pressures in finite element
      method (FEM) simulations. The main points in producing the pressure self-focusing
      effect are to use beveled anvils and reach a very thin sample thickness at the
      center. We find that the superposition of torsion in a rotational DAC (RDAC)
      offers drastic enhancement of the pressure self-focusing effect and allows one to
      reach the same pressure under a much lower force and deformation of anvils.

PMID- 28429720
TI  - Noumeavirus replication relies on a transient remote control of the host nucleus.
AB  - Acanthamoeba are infected by a remarkable diversity of large dsDNA viruses, the
      infectious cycles of which have been characterized using genomics,
      transcriptomics and electron microscopy. Given their gene content and the
      persistence of the host nucleus throughout their infectious cycle, the
      Marseilleviridae were initially assumed to fully replicate in the cytoplasm.
      Unexpectedly, we find that their virions do not incorporate the virus-encoded
      transcription machinery, making their replication nucleus-dependent. However,
      instead of delivering their DNA to the nucleus, the Marseilleviridae initiate
      their replication by transiently recruiting the nuclear transcription machinery
      to their cytoplasmic viral factory. The nucleus recovers its integrity after
      becoming leaky at an early stage. This work highlights the importance of virion
      proteomic analyses to complement genome sequencing in the elucidation of the
      replication scheme and evolution of large dsDNA viruses.

PMID- 28429722
TI  - Use of a Visual Aid in addition to a Collector Bag to Evaluate Postpartum Blood
      loss: A Prospective Simulation Study.
AB  - Postpartum hemorrhage (PPH) is one of the most common causes of mortality in
      obstetrics worldwide. The accuracy of estimated blood loss is a priority in
      determining appropriate treatment. Will the additional use of a visual aid
      improve physicians' accuracy in estimating blood loss compared to the use of a
      collector bag and baby scale alone? Simulation training sessions created three
      vaginal delivery scenarios for participants to estimate volumes of blood loss:
      firstly, using only a collector bag and a baby weight scale and secondly, adding
      a visual aid depicting known volumes of blood. The primary endpoint was to
      determine if participants could accurately evaluate blood loss within a 20% error
      margin. The addition of the visual estimator resulted in overestimation of blood
      loss. The rates of participants' estimations were significantly more accurate
      when using the collector bag with the baby weight scale without the addition of
      the visual aid; 85.5% versus 33.3% (p < 0.01) for 350 mL, 88.4% versus 50.7% (p <
      0.01) for 1100 mL and 88.4% versus 78.3% (p < 0.01) for 2500 mL, respectively.
      Additional use of a visual aid with a collector bag does not seem to be useful in
      improving the accuracy in the estimation of blood loss.

PMID- 28429721
TI  - A mouse tissue transcription factor atlas.
AB  - Transcription factors (TFs) drive various biological processes ranging from
      embryonic development to carcinogenesis. Here, we employ a recently developed
      concatenated tandem array of consensus TF response elements (catTFRE) approach to
      profile the activated TFs in 24 adult and 8 fetal mouse tissues on proteome
      scale. A total of 941 TFs are quantitatively identified, representing over 60% of
      the TFs in the mouse genome. Using an integrated omics approach, we present a TF
      network in the major organs of the mouse, allowing data mining and generating
      knowledge to elucidate the roles of TFs in various biological processes,
      including tissue type maintenance and determining the general features of a
      physiological system. This study provides a landscape of TFs in mouse tissues
      that can be used to elucidate transcriptional regulatory specificity and
      programming and as a baseline that may facilitate understanding diseases that are
      regulated by TFs.

PMID- 28429724
TI  - Clonal evolution in myelodysplastic syndromes.
AB  - Cancer development is a dynamic process during which the successive accumulation
      of mutations results in cells with increasingly malignant characteristics. Here,
      we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients
      receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years).
      Whole-exome and targeted deep sequencing at multiple time points during the
      disease course reveals that both linear and branched evolutionary patterns occur
      with and without disease-modifying treatment. The application of disease
      modifying therapy may create an evolutionary bottleneck after which more complex
      MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition,
      subclones that acquired an additional mutation associated with treatment
      resistance (TP53) or disease progression (NRAS, KRAS) may be detected months
      before clinical changes become apparent. Monitoring the genetic landscape during
      the disease may help to guide treatment decisions.

PMID- 28429725
TI  - Estrogen reprograms the activity of neutrophils to foster protumoral
      microenvironment during mammary involution.
AB  - Epidemiological studies have indicated increased risk for breast cancer within 10
      years of childbirth. Acute inflammation during mammary involution has been
      suggested to promote this parity-associated breast cancer. We report here that
      estrogen exacerbates mammary inflammation during involution. Microarray analysis
      shows that estrogen induces an extensive proinflammatory gene signature in the
      involuting mammary tissue. This is associated with estrogen-induced neutrophil
      infiltration. Furthermore, estrogen induces the expression of protumoral
      cytokines/chemokines, COX-2 and tissue-remodeling enzymes in isolated mammary
      neutrophils and systemic neutrophil depletion abolished estrogen-induced
      expression of these genes in mammary tissue. More interestingly, neutrophil
      depletion diminished estrogen-induced growth of ERalpha-negative mammary tumor
      4T1 in Balb/c mice. These findings highlight a novel aspect of estrogen action
      that reprograms the activity of neutrophils to create a pro-tumoral
      microenvironment during mammary involution. This effect on the microenvironment
      would conceivably aggravate its known neoplastic effect on mammary epithelial
      cells.

PMID- 28429726
TI  - Verteporfin-induced formation of protein cross-linked oligomers and high
      molecular weight complexes is mediated by light and leads to cell toxicity.
AB  - Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal
      laser light (689 nm) in the presence of oxygen activates the drug to produce
      highly reactive oxygen radicals, resulting in local cell and tissue damage.
      However, it has also been shown that Verteporfin can have non-photoactivated
      effects such as interference with the YAP-TEAD complex of the HIPPO pathway,
      resulting in growth inhibition of several neoplasias. More recently, it was
      proposed that, another non-light mediated effect of VP is the formation of cross
      linked oligomers and high molecular weight protein complexes (HMWC) that are
      hypothesized to interfere with autophagy and cell growth. Here, in a series of
      experiments, using human uveal melanoma cells (MEL 270), human embryonic kidney
      cells (HEK) and breast cancer cells (MCF7) we showed that Verteporfin-induced
      HMWC require the presence of light. Furthermore, we showed that the mechanism of
      this cross-linking, which involves both singlet oxygen and radical generation,
      can occur very efficiently even after lysis of the cells, if the lysate is not
      protected from ambient light. This work offers a better understanding regarding
      VP's mechanisms of action and suggests caution when one studies the non-light
      mediated actions of this drug.

PMID- 28429727
TI  - Selection of relatively exact reference genes for gene expression studies in
      goosegrass (Eleusine indica) under herbicide stress.
AB  - Goosegrass (Eleusine indica) is one of the most serious annual grassy weeds
      worldwide, and its evolved herbicide-resistant populations are more difficult to
      control. Quantitative real-time PCR (qPCR) is a common technique for
      investigating the resistance mechanism; however, there is as yet no report on the
      systematic selection of stable reference genes for goosegrass. This study
      proposed to test the expression stability of 9 candidate reference genes in
      goosegrass in different tissues and developmental stages and under stress from
      three types of herbicide. The results show that for different developmental
      stages and organs (control), eukaryotic initiation factor 4 A (eIF-4) is the most
      stable reference gene. Chloroplast acetolactate synthase (ALS) is the most stable
      reference gene under glyphosate stress. Under glufosinate stress, eIF-4 is the
      best reference gene. Ubiquitin-conjugating enzyme (UCE) is the most stable
      reference gene under quizalofop-p-ethyl stress. The gene eIF-4 is the recommended
      reference gene for goosegrass under the stress of all three herbicides. Moreover,
      pairwise analysis showed that seven reference genes were sufficient to normalize
      the gene expression data under three herbicides treatment. This study provides a
      list of reliable reference genes for transcript normalization in goosegrass,
      which will facilitate resistance mechanism studies in this weed species.

PMID- 28429728
TI  - A Formulated TLR7/8 Agonist is a Flexible, Highly Potent and Effective Adjuvant
      for Pandemic Influenza Vaccines.
AB  - Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have
      been transmitted from avian hosts to humans. The severity of H5N1 infection in
      humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and
      temporally, make generation of an effective vaccine a global public health
      priority. An effective H5N1 vaccine must ultimately provide protection against
      viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant
      formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre
      clinical models. However, many of these agonist molecules have proven difficult
      to develop clinically. Here, we describe comprehensive adjuvant formulation
      development of the imidazoquinoline TLR-7/8 agonist 3M-052, in combination with
      H5N1 hemagglutinin (HA) based antigens. We find that 3M-052 in multiple
      formulations protects both mice and ferrets from lethal H5N1 homologous virus
      challenge. Furthermore, we conclusively demonstrate the ability of 3M-052
      adjuvant formulations to broaden responses to H5N1 HA based antigens, and show
      that this broadening is functional using a heterologous lethal virus challenge in
      ferrets. Given the extensive clinical use of imidazoquinoline TLR agonists for
      other indications, these studies identify multiple adjuvant formulations which
      may be rapidly advanced into clinical trials in an H5N1 vaccine.

PMID- 28429729
TI  - Weak connections form an infinite number of patterns in the brain.
AB  - Recently, much attention has been paid to interpreting the mechanisms for memory
      formation in terms of brain connectivity and dynamics. Within the plethora of
      collective states a complex network can exhibit, we show that the phenomenon of
      Collective Almost Synchronisation (CAS), which describes a state with an infinite
      number of patterns emerging in complex networks for weak coupling strengths,
      deserves special attention. We show that a simulated neuron network with neurons
      weakly connected does produce CAS patterns, and additionally produces an output
      that optimally model experimental electroencephalograph (EEG) signals. This work
      provides strong evidence that the brain operates locally in a CAS regime,
      allowing it to have an unlimited number of dynamical patterns, a state that could
      explain the enormous memory capacity of the brain, and that would give support to
      the idea that local clusters of neurons are sufficiently decorrelated to
      independently process information locally.

PMID- 28429730
TI  - New Bicyclic Cembranoids from the South China Sea Soft Coral Sarcophyton
      trocheliophorum.
AB  - Nine new bicyclic cembranoids, sarcophytrols M-U(1-9), were isolated from the
      South China Sea soft coral Sarcophyton trocheliophorum as minor components, along
      with one known related cembranoid 10. Their structures were elucidated by
      detailed spectroscopic analysis and chemical conversion. The chemical structures
      of these metabolites are characterized by the different patterns of the
      additional cyclization within the 14-member skeleton, which leading to the
      formation of furan, pyran, oxepane, and peroxyl rings, respectively. Among them,
      sarcophytrols R and S(6 and 7) share a rare decaryiol skeleton with an unusual
      C12/C15 cyclization. In addition, the absolute configurations of sarcophytrols M
      and T(1 and 8) were determined by the modified Mosher's method. The research of
      these new secondary metabolites provided a further understanding of the diversity
      of cyclized cembranoids from the title species.

PMID- 28429731
TI  - The evolutionary life cycle of the polysaccharide biosynthetic gene cluster based
      on the Sphingomonadaceae.
AB  - Although clustering of genes from the same metabolic pathway is a widespread
      phenomenon, the evolution of the polysaccharide biosynthetic gene cluster remains
      poorly understood. To determine the evolution of this pathway, we identified a
      scattered production pathway of the polysaccharide sanxan by Sphingomonas
      sanxanigenens NX02, and compared the distribution of genes between sphingan
      producing and other Sphingomonadaceae strains. This allowed us to determine how
      the scattered sanxan pathway developed, and how the polysaccharide gene cluster
      evolved. Our findings suggested that the evolution of microbial polysaccharide
      biosynthesis gene clusters is a lengthy cyclic process comprising cluster 1 ->
      scatter -> cluster 2. The sanxan biosynthetic pathway proved the existence of a
      dispersive process. We also report the complete genome sequence of NX02, in which
      we identified many unstable genetic elements and powerful secretion systems.
      Furthermore, nine enzymes for the formation of activated precursors, four
      glycosyltransferases, four acyltransferases, and four polymerization and export
      proteins were identified. These genes were scattered in the NX02 genome, and the
      positive regulator SpnA of sphingans synthesis could not regulate sanxan
      production. Finally, we concluded that the evolution of the sanxan pathway was
      independent. NX02 evolved naturally as a polysaccharide producing strain over a
      long-time evolution involving gene acquisitions and adaptive mutations.

PMID- 28429732
TI  - Long term stability and infectivity of herpesviruses in water.
AB  - For viruses to utilize environmental vectors (hard surfaces, soil, water) for
      transmission, physical and chemical stability is a prerequisite. There are many
      factors including pH, salinity, temperature, and turbidity that are known to
      contribute to the ability of viruses to persist in water. Equine herpesvirus type
      1 (EHV-1) is a pathogenic alphaherpesvirus associated with domestic horses and
      wild equids. EHV-1 and recombinants of EHV-1 and EHV-9 are able to cause
      infections in non-equid animal species, particularly in captive settings. Many of
      the captive non-equid mammals are not naturally sympatric with equids and do not
      share enclosures, however, in many cases water sources may overlap. Similarly, in
      the wild, equids encounter many species at waterholes in times of seasonal
      drought. Therefore, we hypothesized that EHV-1 is stable in water and that water
      may act as a vector for EHV-1. In order to establish the conditions promoting or
      hindering EHV-1 longevity, infectivity and genomic stability in water; we exposed
      EHV-1 to varied water environments (pH, salinity, temperature, and turbidity) in
      controlled experiments over 21 days. The presence and infectivity of the virus
      was confirmed by both qPCR and cell culture experiments. Our results show that
      EHV-1 remains stable and infectious under many conditions in water for up to
      three weeks.

PMID- 28429733
TI  - Sites of overt and covert attention define simultaneous spatial reference centers
      for visuomotor response.
AB  - The site of overt attention (fixation point) defines a spatial reference center
      that affects visuomotor response as indicated by the stimulus-response
      compatibility (SRC) effect: When subjects press, e.g., a left key to report
      stimuli, their reaction time is shorter when stimuli appear to the left than to
      the right of the fixation. Covert attention to a peripheral site appears to
      define a similar reference center but previous studies did not control for
      confounding spatiotemporal factors or investigate the relationship between overt-
      and covert-attention-defined centers. Using an eye tracker to monitor fixation,
      we found an SRC effect relative to the site of covert attention induced by a
      flashed cue dot, and a concurrent reduction, but not elimination, of the overt
      attention SRC effect. The two SRC effects jointly determined the overall motor
      reaction time. Since trials with different cue locations were randomly
      interleaved, the integration of the two reference centers must be updated online.
      When the cue was invalid and diminished covert attention, the covert-attention
      SRC effect disappeared and the overt-attention SRC effect retained full strength,
      excluding non-attention-based interpretations. We conclude that both covert- and
      overt-attention sites define visual reference centers that simultaneously
      contribute to motor response.

PMID- 28429734
TI  - Neuroprotective pentapeptide CN-105 is associated with reduced sterile
      inflammation and improved functional outcomes in a traumatic brain injury murine
      model.
AB  - At present, there are no proven pharmacological treatments demonstrated to
      improve long term functional outcomes following traumatic brain injury(TBI). In
      the setting of non-penetrating TBI, sterile brain inflammatory responses are
      associated with the development of cerebral edema, intracranial hypertension, and
      secondary neuronal injury. There is increasing evidence that endogenous
      apolipoprotein E(apoE) modifies the neuroinflammatory response through its role
      in downregulating glial activation, however, the intact apoE holoprotein does not
      cross the blood-brain barrier due to its size. To address this limitation, we
      developed a small 5 amino acid apoE mimetic peptide(CN-105) that mimics the polar
      face of the apoE helical domain involved in receptor interactions. The goal of
      this study was to investigate the therapeutic potential of CN-105 in a murine
      model of closed head injury. Treatment with CN-105 was associated with a durable
      improvement in functional outcomes as assessed by Rotarod and Morris Water Maze
      and a reduction in positive Fluoro-Jade B stained injured neurons and microglial
      activation. Administration of CN-105 was also associated with reduction in mRNA
      expression of a subset of inflammatory and immune-related genes.

PMID- 28429735
TI  - Phylogenetic analysis of metastatic progression in breast cancer using somatic
      mutations and copy number aberrations.
AB  - Several studies using genome-wide molecular techniques have reported various
      degrees of genetic heterogeneity between primary tumours and their distant
      metastases. However, it has been difficult to discern patterns of dissemination
      owing to the limited number of patients and available metastases. Here, we use
      phylogenetic techniques on data generated using whole-exome sequencing and copy
      number profiling of primary and multiple-matched metastatic tumours from ten
      autopsied patients to infer the evolutionary history of breast cancer
      progression. We observed two modes of disease progression. In some patients, all
      distant metastases cluster on a branch separate from their primary lesion. Clonal
      frequency analyses of somatic mutations show that the metastases have a
      monoclonal origin and descend from a common 'metastatic precursor'.
      Alternatively, multiple metastatic lesions are seeded from different clones
      present within the primary tumour. We further show that a metastasis can be
      horizontally cross-seeded. These findings provide insights into breast cancer
      dissemination.

PMID- 28429736
TI  - Single-step One-pot Synthesis of TiO2 Nanosheets Doped with Sulfur on Reduced
      Graphene Oxide with Enhanced Photocatalytic Activity.
AB  - A hybrid photocatalyst based on anatase TiO2 was designed by doping TiO2 with
      sulfur and incorporating reduced graphene oxide (TiO2-S/rGO hybrid), with an aim
      to narrow the band gap to potentially make use of visible light and decrease the
      recombination of excitons, respectively. This TiO2-S/rGO hybrid was successfully
      synthesized using a one-pot hydrothermal method via single-step reaction. The
      structure and morphology of the TiO2-S/rGO hybrid catalyst was carefully
      characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy
      (XPS). Its photocatalytic reactivity was evaluated by the degradation of methyl
      blue. The results showed that both the doping of sulfur and the introduction of
      rGO worked as designed, and the TiO2-S/rGO hybrid exhibited high photocatalytic
      activity under simulated sunlight. Considering both the facile and scalable
      reaction to synthesize TiO2-S/rGO hybrid, and its excellent photocatalytic
      performance, such TiO2-S/rGO hybrids are expect to find practical applications in
      environmental and energy sectors.

PMID- 28429737
TI  - The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces
      nutrient flexibility.
AB  - As noted by Warburg, many cancer cells depend on the consumption of glucose. We
      performed a genetic screen to identify factors responsible for glucose addiction
      and recovered the two subunits of the xCT antiporter (system xc-), which plays an
      antioxidant role by exporting glutamate for cystine. Disruption of the xCT
      antiporter greatly improves cell viability after glucose withdrawal, because
      conservation of glutamate enables cells to maintain mitochondrial respiration. In
      some breast cancer cells, xCT antiporter expression is upregulated through the
      antioxidant transcription factor Nrf2 and contributes to their requirement for
      glucose as a carbon source. In cells carrying patient-derived mitochondrial DNA
      mutations, the xCT antiporter is upregulated and its inhibition improves
      mitochondrial function and cell viability. Therefore, although upregulation of
      the xCT antiporter promotes antioxidant defence, it antagonizes glutamine
      metabolism and restricts nutrient flexibility. In cells with mitochondrial
      dysfunction, the potential utility of xCT antiporter inhibition should be further
      tested.

PMID- 28429739
TI  - A large-scale benchmark of gene prioritization methods.
AB  - In order to maximize the use of results from high-throughput experimental
      studies, e.g. GWAS, for identification and diagnostics of new disease-associated
      genes, it is important to have properly analyzed and benchmarked gene
      prioritization tools. While prospective benchmarks are underpowered to provide
      statistically significant results in their attempt to differentiate the
      performance of gene prioritization tools, a strategy for retrospective
      benchmarking has been missing, and new tools usually only provide internal
      validations. The Gene Ontology(GO) contains genes clustered around annotation
      terms. This intrinsic property of GO can be utilized in construction of robust
      benchmarks, objective to the problem domain. We demonstrate how this can be
      achieved for network-based gene prioritization tools, utilizing the FunCoup
      network. We use cross-validation and a set of appropriate performance measures to
      compare state-of-the-art gene prioritization algorithms: three based on network
      diffusion, NetRank and two implementations of Random Walk with Restart, and
      MaxLink that utilizes network neighborhood. Our benchmark suite provides a
      systematic and objective way to compare the multitude of available and future
      gene prioritization tools, enabling researchers to select the best gene
      prioritization tool for the task at hand, and helping to guide the development of
      more accurate methods.

PMID- 28429738
TI  - Fatty acid synthase cooperates with protrudin to facilitate membrane outgrowth of
      cellular protrusions.
AB  - Cellular protrusion formation capacity is a key feature of developing neurons and
      many eukaryotic cells. However, the mechanisms underlying membrane growth in
      protrusion formation are largely unclear. In this study, photo-reactive unnatural
      amino acid 3-(3-methyl-3H-diazirin-3-yl)-propamino-carbonyl-Nepsilon-l-lysine was
      incorporated by a genetic code expansion strategy into protrudin, a protein
      localized in acidic endosomes and in the endoplasmic reticulum, that induces
      cellular protrusion and neurite formation. The modified protrudin was used for
      covalent trapping of protrudin-interacting proteins in living cells. Fatty acid
      synthase (FASN), which synthesizes free fatty acids, was identified to
      transiently interact with protrudin. Further characterization revealed a unique
      cooperation mechanism in which protrudin cooperates with FASN to facilitate
      cellular protrusion formation. This work reveals a novel mechanism involved in
      protrusion formation that is dependent on transient interaction between FASN and
      protrudin, and establishes a creative strategy to investigate transient protein
      protein interactions in mammalian cells.

PMID- 28429740
TI  - Micelle-template synthesis of hollow silica spheres for improving water vapor
      permeability of waterborne polyurethane membrane.
AB  - Hollow silica spheres (HSS) with special interior spaces, high specific surface
      area and excellent adsorption and permeability performance were synthesized via
      micelle-template method using cetyl trimethyl ammonium bromide (CTAB) micelles as
      soft template and tetraethoxysilane (TEOS) as silica precursor. SEM, TEM, FT-IR,
      XRD, DLS and BET-BJH were carried out to characterize the morphology and
      structure of as-obtained samples. The results demonstrated that the samples were
      amorphous with a hollow structure and huge specific surface area. The growth of
      HSS was an inward-growth mechanism along template. Notably, we have provided a
      new and interesting fundamental principle for HSS materials by precisely
      controlling the ethanol-to-water volume ratio. In addition, the as-obtained HSS
      were mixed with waterborne polyurethane (WPU) to prepare WPU/HSS composite
      membrane. Various characterizations (SEM, TEM, FT-IR and TGA) revealed the
      morphology, polydispersity and adherence between HSS and WPU. Performance tests
      showed that the introduction of HSS can improve the water vapor permeability of
      composite membrane, promoting its water resistance and mechanical performance at
      the same time.

PMID- 28429741
TI  - The risk of translaminar screw fixation to the transverse foramen of the lower
      cervical spine: a computed tomography study.
AB  - Translaminar screw fixation (TSF) of the axis is considered as an efficient, safe
      and simple surgical procedure, however the study of the potential risk of TSF to
      the transverse foramen in lower cervical spine is lacked. Head-neck CT images of
      60 patients were included in this study. Maximum screw length, laminar thickness,
      the screw angle and the laminar height were measured. The feasibility of 3.5-mm
      diameter screw fixation and the potential risk of transverse foramen injury was
      analyzed. The TSF was safe at C3 and C4, but risky to the transverse foraman at a
      rate of 8.7% at C5 (0% on the left side and 20% on the right side), 33.3% at C6
      (24.4% on the left side and 42.9% on the right side). C7 had the highest 77.8%
      rate (65.5% on the left side and 89.8% on the right side). The safe screw length
      was 27.7 mm at C3, 27.4 mm at C4, 28.0 mm at C5, 25.6 mm at C6 and 25.5 mm at C7,
      respectively. The present study showed that translaminar screw could place the
      transverse foramen of C5-C7 at risk. Preoperative CT scanning was necessary for
      safe screw placement.

PMID- 28429742
TI  - Crossing lines: a multidisciplinary framework for assessing connectivity of
      hammerhead sharks across jurisdictional boundaries.
AB  - Conservation and management of migratory species can be complex and challenging.
      International agreements such as the Convention on Migratory Species (CMS)
      provide policy frameworks, but assessments and management can be hampered by lack
      of data and tractable mechanisms to integrate disparate datasets. An assessment
      of scalloped (Sphyrna lewini) and great (Sphyrna mokarran) hammerhead population
      structure and connectivity across northern Australia, Indonesia and Papua New
      Guinea (PNG) was conducted to inform management responses to CMS and Convention
      on International Trade in Endangered Species listings of these species. An
      Integrated Assessment Framework (IAF) was devised to systematically incorporate
      data across jurisdictions and create a regional synopsis, and amalgamated a suite
      of data from the Australasian region. Scalloped hammerhead populations are
      segregated by sex and size, with Australian populations dominated by juveniles
      and small adult males, while Indonesian and PNG populations included large adult
      females. The IAF process introduced genetic and tagging data to produce
      conceptual models of stock structure and movement. Several hypotheses were
      produced to explain stock structure and movement patterns, but more data are
      needed to identify the most likely hypothesis. This study demonstrates a process
      for assessing migratory species connectivity and highlights priority areas for
      hammerhead management and research.

PMID- 28429743
TI  - Novel SUMO-Protease SENP7S Regulates beta-catenin Signaling and Mammary
      Epithelial Cell Transformation.
AB  - SUMO post-translational modification of proteins or SUMOylation ensures normal
      cell function. Disruption of SUMO dynamics prompts various pathophysiological
      conditions, including cancer. The burden of deSUMOylating the large SUMO-proteome
      rests on 6 full-length mammalian SUMO-proteases or SENP. While multiple SENP
      isoforms exist, the function of these isoforms remains undefined. We now
      delineate the biological role of a novel SENP7 isoform SENP7S in mammary
      epithelial cells. SENP7S is the predominant SENP transcript in human mammary
      epithelia but is significantly reduced in precancerous ductal carcinoma in situ
      and all breast cancer subtypes. Like other SENP family members, SENP7S has SUMO
      isopeptidase activity but unlike full-length SENP7L, SENP7S is localized in the
      cytosol. In vivo, SUMOylated beta-catenin and Axin1 are both SENP7S-substrates.
      With knockdown of SENP7S in mammary epithelial cells, Axin1-beta-catenin
      interaction is lost and beta-catenin escapes ubiquitylation-dependent proteasomal
      degradation. SUMOylated beta-catenin accumulates at the chromatin and activates
      multiple oncogenes. Hence, non-tumorigenic MCF10-2A cells with reduced SENP7S
      exhibit greater cell proliferation and anchorage-dependent growth. SENP7S
      depletion directly potentiates tumorigenic properties of MCF10-2A cells with
      induction of anchorage-independent growth and self-renewal in 3D-spheroid
      conditions. Collectively, the results identify SENP7S as a novel mediator of beta
      catenin signaling and normal mammary epithelial cell physiology.

PMID- 28429744
TI  - A Forest of Sub-1.5-nm-wide Single-Walled Carbon Nanotubes over an Engineered
      Alumina Support.
AB  - A precise control of the dimension of carbon nanotubes (CNTs) in their vertical
      array could enable many promising applications in various fields. Here, we
      demonstrate the growth of vertically aligned, single-walled CNTs (VA-SWCNTs) with
      diameters in the sub-1.5-nm range (0.98 +/- 0.24 nm), by engineering a catalyst
      support layer of alumina via thermal annealing followed by ion beam treatment. We
      find out that the ion beam bombardment on the alumina allows the growth of ultra
      narrow nanotubes, whereas the thermal annealing promotes the vertical alignment
      at the expense of enlarged diameters; in an optimal combination, these two
      effects can cooperate to produce the ultra-narrow VA-SWCNTs. According to micro-
      and spectroscopic characterizations, ion beam bombardment amorphizes the alumina
      surface to increase the porosity, defects, and oxygen-laden functional groups on
      it to inhibit Ostwald ripening of catalytic Fe nanoparticles effectively, while
      thermal annealing can densify bulk alumina to prevent subsurface diffusion of the
      catalyst particles. Our findings contribute to the current efforts of precise
      diameter control of VA-SWCNTs, essential for applications such as membranes and
      energy storage devices.

PMID- 28429745
TI  - High Temperature Terahertz Detectors Realized by a GaN High Electron Mobility
      Transistor.
AB  - In this work, a high temperature THz detector based on a GaN high electron
      mobility transistor (HEMT) with nano antenna structures was fabricated and
      demonstrated to be able to work up to 200  degrees C. The THz responsivity and
      noise equivalent power (NEP) of the device were characterized at 0.14 THz
      radiation over a wide temperature range from room temperature to 200  degrees C.
      A high responsivity Rv of 15.5 and 2.7 kV/W and a low NEP of 0.58 and 10 pW/Hz0.5
      were obtained at room temperature and 200  degrees C, respectively. The
      advantages of the GaN HEMT over other types of field effect transistors for high
      temperature terahertz detection are discussed. The physical mechanisms
      responsible for the temperature dependence of the responsivity and NEP of the GaN
      HEMT are also analyzed thoroughly.

PMID- 28429746
TI  - The small G protein Arf6 expressed in keratinocytes by HGF stimulation is a
      regulator for skin wound healing.
AB  - The earlier step of cutaneous wound healing process, re-epithelialization of the
      wounded skin, is triggered by a variety of growth factors. However, molecular
      mechanisms through which growth factors trigger skin wound healing are less
      understood. Here, we demonstrate that hepatocyte growth factor (HGF)/c-Met
      signaling-induced expression of the small G protein Arf6 mRNA in keratinocytes is
      essential for the skin wound healing. Arf6 mRNA expression was dramatically
      induced in keratinocytes at the wounded skin, which was specifically suppressed
      by the c-Met inhibitor. Wound healing of the skin was significantly delayed in
      keratinocyte-specific Arf6 conditional knockout mice. Furthermore, Arf6 deletion
      from keratinocytes remarkably suppressed HGF-stimulated cell migration and
      peripheral membrane ruffle formation, but did not affect skin morphology and
      proliferation/differentiation of keratinocytes. These results are consistent with
      the notion that Arf6 expressed in skin keratinocytes through the HGF/c-Met
      signaling pathway in response to skin wounding plays an important role in skin
      wound healing by regulating membrane dynamics-based motogenic cellular function
      of keratinocytes.

PMID- 28429747
TI  - Imaging genetics approach to Parkinson's disease and its correlation with
      clinical score.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder associated
      with both underlying genetic factors and neuroimaging findings. Existing
      neuroimaging studies related to the genome in PD have mostly focused on certain
      candidate genes. The aim of our study was to construct a linear regression model
      using both genetic and neuroimaging features to better predict clinical scores
      compared to conventional approaches. We obtained neuroimaging and DNA genotyping
      data from a research database. Connectivity analysis was applied to identify
      neuroimaging features that could differentiate between healthy control (HC) and
      PD groups. A joint analysis of genetic and imaging information known as imaging
      genetics was applied to investigate genetic variants. We then compared the
      utility of combining different genetic variants and neuroimaging features for
      predicting the Movement Disorder Society-sponsored unified Parkinson's disease
      rating scale (MDS-UPDRS) in a regression framework. The associative cortex, motor
      cortex, thalamus, and pallidum showed significantly different connectivity
      between the HC and PD groups. Imaging genetics analysis identified PARK2, PARK7,
      HtrA2, GIGYRF2, and SNCA as genetic variants that are significantly associated
      with imaging phenotypes. A linear regression model combining genetic and
      neuroimaging features predicted the MDS-UPDRS with lower error and higher
      correlation with the actual MDS-UPDRS compared to other models using only genetic
      or neuroimaging information alone.

PMID- 28429748
TI  - The pre-Argo ocean reanalyses may be seriously affected by the spatial coverage
      of moored buoys.
AB  - Assimilation methods, meant to constrain divergence of model trajectory from
      reality using observations, do not exactly satisfy the physical laws governing
      the model state variables. This allows mismatches in the analysis in the vicinity
      of observation locations where the effect of assimilation is most prominent.
      These mismatches are usually mitigated either by the model dynamics in between
      the analysis cycles and/or by assimilation at the next analysis cycle. However,
      if the observations coverage is limited in space, as it was in the ocean before
      the Argo era, these mechanisms may be insufficient to dampen the mismatches,
      which we call shocks, and they may remain and grow. Here we show through
      controlled experiments, using real and simulated observations in two different
      ocean models and assimilation systems, that such shocks are generated in the
      ocean at the lateral boundaries of the moored buoy network. They thrive and
      propagate westward as Rossby waves along these boundaries. However, these shocks
      are essentially eliminated by the assimilation of near-homogenous global Argo
      distribution. These findings question the fidelity of ocean reanalysis products
      in the pre-Argo era. For example, a reanalysis that ignores Argo floats and
      assimilates only moored buoys, wrongly represents 2008 as a negative Indian Ocean
      Dipole year.

PMID- 28429749
TI  - Corrigendum: A Doping Lattice of Aluminum and Copper with Accelerated Electron
      Transfer Process and Enhanced Reductive Degradation Performance.

PMID- 28429750
TI  - Correlations of TNF-alpha gene promoter polymorphisms with the risk of thymoma
      associated myasthenia gravis in a northern Chinese Han population.
AB  - This study was performed with the aim to investigate the correlations of tumor
      necrosis factor-alpha (TNF-alpha) gene promoter polymorphisms with the risk of
      thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population.
      Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG
      group) and 293 healthy volunteers (negative control (NC) group) were enrolled in
      this study. Among the MG patients, there were 121 patients with thymoma
      associated MG (T-MG group) and 184 without T-MG (NT-MG group). Enzyme-linked
      immunosorbent assay (ELISA) was used for the serum TNF-alpha level. Polymerase
      chain reaction-restriction fragment length polymorphism was conducted to
      determine genotype and allele frequencies of TNF-alpha gene promoter -1031T/C, 
      857C/T and -863C/A. The haplotype was analyzed with the SHEsis software. Logistic
      regression analysis was performed for correlations between TNF-alpha gene
      promoter polymorphisms and the risk of T-MG. The T-MG group had higher
      frequencies of the CT/TT genotype and T allele of -857C/T than the NT-MG and NC
      groups. The frequencies of the CC genotype and C allele of -1031T/C were higher
      in the T-MG group than in the NT-MG and NC groups, and higher in male patients in
      the T-MG group than in male patients in the NC group. TTA and TTC haplotypes
      exhibited lower frequencies in the T-MG group than in the NT-MG group. The ocular
      MG patients exhibited lower frequencies of the TT genotype and T allele of 
      857C/T than the generalized MG patients did. The TNF-alpha level was elevated in
      the T-MG group compared with that in the NC and NT-MG groups, indicating that the
      TC+CC and CT+TT genotypes were increased compared with the TT and CC genotypes in
      the -1031T/C and -857C/T, respectively. Logistic regression analysis suggested
      that expressions of anti-acetylcholine receptor antibodies, Osserman's
      classification, -1031T/C and -857C/T polymorphisms and the TTA haplotype were the
      independent risk factors for T-MG. These findings reveal that TNF-alpha -1031T/C
      and -857C/T polymorphisms and the TTA haplotype may be correlated with the
      occurrence of T-MG in a Northern Chinese Han population.

PMID- 28429751
TI  - Preclinical study of rAAV2-sTRAIL: pharmaceutical efficacy, biodistribution and
      safety in animals.
AB  - The recombinant sTRAIL has been in clinical trial for various human malignancies.
      However, the half-life time of sTRAIL is very short, which might be an important
      factor influencing its clinical efficacy for cancer therapy. We previously
      reported the recombinant adeno-associated virus (AAV)-encoding sTRAIL95-281
      mediated sTRAIL expression in vivo up to 8 months and suppressed tumor growth
      markedly in mouse xenografts. In the present study, we further evaluated the
      clinical potency for cancer gene therapy and the safety in mouse and non-human
      primates. The mouse models with HCT-116, NCI-H460 and BEL-7402 cancers were
      injected intraperitoneally with a single dose of 1.0 * 1011, 1.0 * 1010 and 1.0 *
      109 vg of rAAV2-sTRAIL95-281 virus, respectively. The cynomolgus monkeys were
      injected (i.m.) with a single dose of rAAV2-sTRAIL95-281 of 1 * 1011, 3 * 1011
      and 1 * 1012 vg, corresponding to 6-, 20- and 60-fold of intended use dosage for
      humans, respectively. The efficacy, pharmacology and toxicity of rAAV-sTRAIL in
      the animals were analyzed accordingly. The tumor inhibitory rates reached 44-76%,
      48-52% and 55-74% in the three tumor models, respectively, and they had no
      influence on mouse spontaneous activity. Administration (s.c.) of a single dose
      of rAAV2-sTRAIL95-281 virus of 1.0 * 109 or 1.0 * 1010 vg in mice with implanted
      tumor led to mainly distribution in the spleen, liver, implanted tumor, blood,
      injected site of muscle and bone marrow. Two weeks later, there was no rAAV2
      sTRAIL95-281 detected in blood and bone marrow, and it significantly decreased in
      other tissues and organs and then gradually cleared away in 4-12 weeks after
      administration. There was no rAAV2-sTRAIL accumulation in the animal's body and
      no influence on the body weights. Administration (i.v.) did not cause animal
      death, and no dose-related abnormal clinical symptoms were found in the mice.
      There were no abnormal tissue and organ found in all animals. Long-term toxicity
      test in cynomolgus monkeys did not cause rAAV2-sTRAIL95-281-related toxic and
      side effects, except that anti-AAV and anti-sTRAIL antibodies were generated. In
      conclusion, these data demonstrated that administration of rAAV2-sTRAIL95-281 in
      mice and in cynomolgus monkeys is safe without obvious toxic and side effects to
      the animals, and throw light on pharmacokinetics and safety in human clinical
      trials for cancer gene therapy.

PMID- 28429752
TI  - lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by
      association with E2F1.
AB  - Lung cancer is the leading cause of cancer-related death around the world. Long
      noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development.
      However, only a few lncRNAs have been functionally characterized. In the present
      study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by
      TGFbeta) expression on non-small cell lung cancer (NSCLC) cell phenotype with the
      gain-of-function and loss-of-function assays. We found that ectopic expression or
      knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation,
      respectively. Moreover, we also showed that lncRNA-HIT interacted with E2F1 to
      regulate its target genes, such as Survivin, FOXM1, SKP2, NELL2 and DOK1.
      Collectively, our findings indicated that lncRNA-HIT affected the proliferation
      of NSCLC cells at least in part via regulating the occupancy of E2F1 in the
      promoter regions of its target genes. The lncRNA-HIT-E2F1 complex may be a
      potential target for NSCLC treatment.

PMID- 28429753
TI  - Impact of Surface-Active Guanidinium-, Tetramethylguanidinium-, and Cholinium
      Based Ionic Liquids on Vibrio Fischeri Cells and Dipalmitoylphosphatidylcholine
      Liposomes.
AB  - We investigated the toxicological effect of seven novel cholinium, guanidinium,
      and tetramethylguanidinium carboxylate ionic liquids (ILs) from an
      ecotoxicological point of view. The emphasis was on the potential structure
      toxicity dependency of these surface-active ILs in aqueous environment. The
      median effective concentrations (EC50) were defined for each IL using Vibrio
      (Aliivibrio) fischeri marine bacteria. Dipalmitoylphosphatidylcholine (DPPC)
      liposomes were used as biomimetic lipid membranes to study the interactions
      between the surface-active ILs and the liposomes. The interactions were
      investigated by following the change in the DPPC phase transition behaviour using
      differential scanning calorimetry (DSC). Critical micelle concentrations for the
      ILs were determined to clarify the analysis of the toxicity and the interaction
      results. Increasing anion alkyl chain length increased the toxicity, whereas
      branching of the chain decreased the toxicity of the ILs. The toxicity of the ILs
      in this study was mainly determined by the surface-active anions, while cations
      induced a minor impact on the toxicity. In the DSC experiments the same trend was
      observed for all the studied anions, whereas the cations seemed to induce more
      variable impact on the phase transition behaviour. Toxicity measurements combined
      with liposome interaction studies can provide a valuable tool for assessing the
      mechanism of toxicity.

PMID- 28429754
TI  - Real-Time Detection of Tsunami Ionospheric Disturbances with a Stand-Alone GNSS
      Receiver: A Preliminary Feasibility Demonstration.
AB  - It is well known that tsunamis can produce gravity waves that propagate up to the
      ionosphere generating disturbed electron densities in the E and F regions. These
      ionospheric disturbances can be studied in detail using ionospheric total
      electron content (TEC) measurements collected by continuously operating ground
      based receivers from the Global Navigation Satellite Systems (GNSS). Here, we
      present results using a new approach, named VARION (Variometric Approach for Real
      Time Ionosphere Observation), and estimate slant TEC (sTEC) variations in a real
      time scenario. Using the VARION algorithm we compute TEC variations at 56 GPS
      receivers in Hawaii as induced by the 2012 Haida Gwaii tsunami event. We observe
      TEC perturbations with amplitudes of up to 0.25 TEC units and traveling
      ionospheric perturbations (TIDs) moving away from the earthquake epicenter at an
      approximate speed of 316 m/s. We perform a wavelet analysis to analyze localized
      variations of power in the TEC time series and we find perturbation periods
      consistent with a tsunami typical deep ocean period. Finally, we present
      comparisons with the real-time tsunami MOST (Method of Splitting Tsunami) model
      produced by the NOAA Center for Tsunami Research and we observe variations in TEC
      that correlate in time and space with the tsunami waves.

PMID- 28429755
TI  - Opossum APOBEC1 is a DNA mutator with retrovirus and retroelement restriction
      activity.
AB  - APOBEC3s (A3s) are single-stranded DNA cytosine deaminases that provide innate
      immune defences against retroviruses and mobile elements. A3s are specific to
      eutherian mammals because no direct homologs exist at the syntenic genomic locus
      in metatherian (marsupial) or prototherian (monotreme) mammals. However, the A3s
      in these species have the likely evolutionary precursors, the antibody gene
      deaminase AID and the RNA/DNA editing enzyme APOBEC1 (A1). Here, we used cell
      culture-based assays to determine whether opossum A1 restricts the infectivity of
      retroviruses including human immunodeficiency virus type 1 (HIV-1) and the
      mobility of LTR/non-LTR retrotransposons. Opossum A1 partially inhibited HIV-1,
      as well as simian immunodeficiency virus (SIV), murine leukemia virus (MLV), and
      the retrotransposon MusD. The mechanism of inhibition required catalytic
      activity, except for human LINE1 (L1) restriction, which was deamination
      independent. These results indicate that opossum A1 functions as an innate
      barrier to infection by retroviruses such as HIV-1, and controls LTR/non-LTR
      retrotransposition in marsupials.

PMID- 28429756
TI  - A non-canonical binding interface in the crystal structure of HIV-1 gp120 core in
      complex with CD4.
AB  - Numerous crystal structures of HIV gp120 have been reported, alone or with
      receptor CD4 and cognate antibodies; however, no sole gp120/CD4 complex without
      stabilization by an antibody is available. Here, we report a crystal structure of
      the gp120/CD4 complex without the aid of an antibody from HIV-1 CRF07_BC, a
      strain circulating in China. Interestingly, in addition to the canonical binding
      surface, a second interacting interface was identified. A mutagenesis study on
      critical residues revealed that the stability of this interface is important for
      the efficiency of Env-mediated membrane fusion. Furthermore, we found that a
      broad neutralizing antibody, ibalizumab, which targets CD4 in the absence of
      gp120, occupies the same binding surface as the second interface identified here
      on gp120. Therefore, we identified the possibility of the involvement of a second
      gp120-CD4 interaction interface during viral entry, and also provided a
      reasonable explanation for the broad activity of neutralizing antibody
      ibalizumab.

PMID- 28429757
TI  - Soft Electronics Enabled Ergonomic Human-Computer Interaction for Swallowing
      Training.
AB  - We introduce a skin-friendly electronic system that enables human-computer
      interaction (HCI) for swallowing training in dysphagia rehabilitation. For an
      ergonomic HCI, we utilize a soft, highly compliant ("skin-like") electrode, which
      addresses critical issues of an existing rigid and planar electrode combined with
      a problematic conductive electrolyte and adhesive pad. The skin-like electrode
      offers a highly conformal, user-comfortable interaction with the skin for long
      term wearable, high-fidelity recording of swallowing electromyograms on the chin.
      Mechanics modeling and experimental quantification captures the ultra-elastic
      mechanical characteristics of an open mesh microstructured sensor, conjugated
      with an elastomeric membrane. Systematic in vivo studies investigate the
      functionality of the soft electronics for HCI-enabled swallowing training, which
      includes the application of a biofeedback system to detect swallowing behavior.
      The collection of results demonstrates clinical feasibility of the ergonomic
      electronics in HCI-driven rehabilitation for patients with swallowing disorders.

PMID- 28429759
TI  - Dual mechanisms of grain refinement in a FeCoCrNi high-entropy alloy processed by
      high-pressure torsion.
AB  - An equiatomic FeCoCrNi high-entropy alloy with a face-centered cubic structure
      was fabricated by a powder metallurgy route, and then processed by high-pressure
      torsion. Detailed microscopy investigations revealed that grain refinement from
      coarse grains to nanocrystalline grains occurred mainly via concurrent nanoband
      (NB) subdivision and deformation twinning. NB-NB, twin-NB and twin-twin
      interactions contributed to the deformation process. The twin-twin interactions
      resulted in severe lattice distortion and accumulation of high densities of
      dislocations in the interaction areas. With increasing strain, NB subdivision and
      interactions between primary twins and inclined secondary stacking faults
      (SFs)/nanotwins occurred. Secondary nanotwins divided the primary twins into many
      equiaxed parts, leading to further grain refinement. The interactions between
      secondary SFs/nanotwins associated with the presence of Shockley partials and
      primary twins also transformed the primary twin boundaries into incoherent high
      angle grain boundaries.

PMID- 28429758
TI  - Intracellular lipid binding protein family diversity from Oyster Crassostrea
      gigas: genomic and structural features of invertebrate lipid transporters.
AB  - Intracellular lipid binding proteins (iLBPs) play a role in the transport and
      cellular uptake of fatty acids and gene expression regulation. The aim of this
      work was to characterize the iLBP gene family of the Pacific oyster Crassostrea
      gigas, one of the most cultivated marine bivalves in the world, using
      bioinformatics and molecular biology approaches. A total of 26 different iLBPs
      transcripts were identified in the Pacific oyster genome, including alternative
      splicing and gene duplication events. The oyster iLBP gene family seems to be
      more expanded than in other invertebrates. Furthermore, 3D structural modeling
      and molecular docking analysis mapped the main amino acids involved in ligand
      interactions, and comparisons to available protein structures from vertebrate
      families revealed new binding cavities. Ten different CgiLBPs were analyzed by
      quantitative PCR in various tissues of C. gigas, which suggested differential
      prevalent gene expression of CgiLBPs among tissue groups. The data indicate a
      wider repertoire of iLBPs in labial palps, a food-sorting tissue. The different
      gene transcription profiles and reported docking systems suggest that the iLBPs
      are a non-generalist ligand binding protein family with specific functions.

PMID- 28429760
TI  - Corrigendum: Selective targeting of HDAC1/2 elicits anticancer effects through
      Gli1 acetylation in preclinical models of SHH Medulloblastoma.

PMID- 28429761
TI  - A specific nanobody prevents amyloidogenesis of D76N beta2-microglobulin in vitro
      and modifies its tissue distribution in vivo.
AB  - Systemic amyloidosis is caused by misfolding and aggregation of globular proteins
      in vivo for which effective treatments are urgently needed. Inhibition of protein
      self-aggregation represents an attractive therapeutic strategy. Studies on the
      amyloidogenic variant of beta2-microglobulin, D76N, causing hereditary systemic
      amyloidosis, have become particularly relevant since fibrils are formed in vitro
      in physiologically relevant conditions. Here we compare the potency of two
      previously described inhibitors of wild type beta2-microglobulin fibrillogenesis,
      doxycycline and single domain antibodies (nanobodies). The beta2-microglobulin 
      binding nanobody, Nb24, more potently inhibits D76N beta2-microglobulin
      fibrillogenesis than doxycycline with complete abrogation of fibril formation. In
      beta2-microglobulin knock out mice, the D76N beta2-microglobulin/ Nb24 pre-formed
      complex, is cleared from the circulation at the same rate as the uncomplexed
      protein; however, the analysis of tissue distribution reveals that the
      interaction with the antibody reduces the concentration of the variant protein in
      the heart but does not modify the tissue distribution of wild type beta2
      microglobulin. These findings strongly support the potential therapeutic use of
      this antibody in the treatment of systemic amyloidosis.

PMID- 28429762
TI  - Annealing Induced Re-crystallization in CH3NH3PbI3-xClx for High Performance
      Perovskite Solar Cells.
AB  - Using poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) as hole
      conductor, a series of inverted planar CH3NH3PbI3-xClx perovskite solar cells
      (PSCs) were fabricated based on perovskite annealed by an improved time
      temperature dependent (TTD) procedure in a flowing nitrogen atmosphere for
      different time. Only after an optimum annealing time, an optimized power
      conversion efficiency of 14.36% could be achieved. To understand their
      performance dependence on annealing time, an in situ real-time synchrotron-based
      grazing incidence X-ray diffraction (GIXRD) was used to monitor a step-by-step
      gradual structure transformation from distinct mainly organic-inorganic hybrid
      materials into highly ordered CH3NH3PbI3 crystal during annealing. However, a re
      crystallization process of perovskite crystal was observed for the first time
      during such an annealing procedure, which helps to enhance the perovskite
      crystallization and preferential orientations. The present GIXRD findings could
      well explain the drops of the open circuit voltage (Voc) and the fill factor (FF)
      during the ramping of temperature as well as the optimized power conversion
      efficiency achieved after an optimum annealing time. Thus, the present study not
      only illustrates clearly the decisive roles of post-annealing in the formation of
      solution-processed perovskite to better understand its formation mechanism, but
      also demonstrates the crucial dependences of device performance on the perovskite
      microstructure in PSCs.

PMID- 28429763
TI  - MicroRNA-26a targets MAPK6 to inhibit smooth muscle cell proliferation and vein
      graft neointimal hyperplasia.
AB  - Neointima formation is the major reason for vein graft failure. However, the
      underlying mechanism is unclear. The aim of this study was to determine the role
      of miR-26a in the development of neointimal hyperplasia of autogenous vein
      grafts. Using autologous jugular vein grafts in the rat carotid artery as a
      model, we found that miR-26a was significantly downregulated in grafted veins as
      well as proliferating vascular smooth muscle cells (VSMCs) stimulated with
      platelet-derived growth factor-BB (PDGF-BB). Overexpression of miR-26a reduced
      the proliferation and migration of VSMCs. Further analysis revealed that the
      effects of miR-26a in VSMCs were mediated by targeting MAPK6 at the mRNA and
      protein levels. Luciferase assays showed that miR-26a repressed wild type (WT)
      MAPK6-3'-UTR-luciferase activity but not mutant MAPK6-3'-UTR-luciferease
      reporter. MAPK6 deficiency reduced proliferation and migration; in contrast,
      overexpression of MAPK6 enhanced the proliferation and migration of VSMCs. This
      study confirmed that neointimal hyperplasia in vein grafts was reduced in vivo by
      up-regulated miR-26a expression. In conclusion, our results showed that miR-26a
      is an important regulator of VSMC functions and neointimal hyperplasia,
      suggesting that miR-26a may be a potential therapeutic target for autologous vein
      graft diseases.

PMID- 28429764
TI  - Fabrication, characterization, and biological evaluation of anti-HER2 indocyanine
      green-doxorubicin-encapsulated PEG-b-PLGA copolymeric nanoparticles for targeted
      photochemotherapy of breast cancer cells.
AB  - In this study, we aimed to develop anti-human epidermal growth factor receptor 2
      (HER2) indocyanine green (ICG)-doxorubicin (DOX)-encapsulated polyethylene glycol
      poly(lactic-co-glycolic acid) diblock copolymeric nanoparticles (HIDPPNPs) to
      explore the co-administration of phototherapy and chemotherapy for HER2
      overexpressing breast cancer, a highly aggressive and medicine-resistant breast
      carcinoma. The HIDPPNPs were fabricated using a solvent evaporation technique
      followed by carbodiimide-mediated antibody conjugation on the nanoparticle
      surface. Compared with freely dissolved ICG, the HIDPPNPs conferred enhanced
      thermal stability to the entrapped ICG, were able to generate a hyperthermia
      effect at concentrations >=1 MUM ICG equivalent and provided increased production
      of singlet oxygen under 808-nm laser irradiation with an intensity of 6 W/cm2.
      Furthermore, the uptake efficiency of the HIDPPNPs in MDA-MB-453/HER2(+) cells
      was approximately 2-fold higher than that in MCF7/HER2(-) cells, demonstrating
      that the HIDPPNPs specifically target HER2-expressing cells. Based on the
      viability analysis, the HIDPPNPs exhibited effective cytotoxicity upon light
      exposure (808 nm; 6 W/cm2), and the resulting cell death rate was even higher
      than that caused by using twice amount of encapsulated DOX or ICG alone. These
      results indicate that the developed HIDPPNPs may serve as a feasible tool for use
      in anti-HER2 breast cancer therapy with reduced chemotoxicity.

PMID- 28429765
TI  - Repolarizing macrophages improves breast cancer therapy.
AB  - Tumor-associated macrophages (TAMs) contribute to breast cancer progression and
      dissemination; TAM-targeting strategies aimed at their reprogramming show
      promising preclinical results. In a new report Guerriero and colleagues
      demonstrate that a novel HDAC Class IIa inhibitor, TMP195, can reprogram
      monocytes and macrophages in the tumor into cells able to sustain a robust CD8 T
      cell-mediated anti-tumoral immune response.

PMID- 28429766
TI  - Beyond growth signaling: Paneth cells metabolically support ISCs.
AB  - Single Lgr5 intestinal stem cells (ISCs) can be expanded in vitro into epithelial
      organoids or "mini-guts", self-organizing cellular structures that recreate the
      intestinal differentiation program; Paneth cells, which constitute the intestinal
      stem cell niche, secrete stem cell growth signals, and are thus essential for
      this process. In a recent paper published in Nature, Rodriguez-Colman et al.
      describe how Paneth cells may be supporting the metabolic state of ISCs.

PMID- 28429767
TI  - Love laughs at Locksmiths: Ubiquitylation of p62 unlocks its autophagy receptor
      potential.
AB  - The multimodular adapter p62/sequestosome-1 plays prominent roles in physiology
      and disease by mediating cell signaling and cargo degradation. The work by Peng
      et al. published recently in Cell Research provides mechanistic insights into
      activation of its autophagy receptor function critical for maintaining cell
      homeostasis during various forms of stress.

PMID- 28429768
TI  - Reassembling embryos in vitro from component stem cells.
AB  - Researchers at the University of Cambridge, UK have succeeded in reconstructing
      mouse embryos by combining pluripotent embryonic and multipotent trophoblast stem
      cells in a 3D scaffold; the study from the laboratory of Professor Zernicka
      Goetz, recently published in Science, provides a break-through tool to probe
      early mammalian development outside the uterus. Achieving a similar feat with
      human cells might necessitate reconsideration of the 14-day rule as a limitation
      of such research.

PMID- 28429769
TI  - Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular
      reprogramming in rod photoreceptors.

PMID- 28429770
TI  - Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity.
AB  - Vascular integrity helps maintain brain microenvironment homeostasis, which is
      critical for the normal development and function of the central nervous system.
      It is known that neural cells can regulate brain vascular integrity. However, due
      to the high complexity of neurovascular interactions involved, understanding of
      the neural regulation of brain vascular integrity is still rudimentary. Using
      intact zebrafish larvae and cultured rodent brain cells, we find that neurons
      transfer miR-132, a highly conserved and neuron-enriched microRNA, via secreting
      exosomes to endothelial cells (ECs) to maintain brain vascular integrity.
      Following translocation to ECs through exosome internalization, miR-132 regulates
      the expression of vascular endothelial cadherin (VE-cadherin), an important
      adherens junction protein, by directly targeting eukaryotic elongation factor 2
      kinase (eef2k). Disruption of neuronal miR-132 expression or exosome secretion,
      or overexpression of vascular eef2k impairs VE-cadherin expression and brain
      vascular integrity. Our study indicates that miR-132 acts as an intercellular
      signal mediating neural regulation of the brain vascular integrity and suggests
      that the neuronal exosome is a novel avenue for neurovascular communication.

PMID- 28429772
TI  - Global profiling of crotonylation on non-histone proteins.

PMID- 28429771
TI  - CRISPR-Cas9-mediated genome editing in one blastomere of two-cell embryos reveals
      a novel Tet3 function in regulating neocortical development.
AB  - Studying the early function of essential genes is an important and challenging
      problem in developmental biology. Here, we established a method for rapidly
      inducing CRISPR-Cas9-mediated mutations in one blastomere of two-cell stage
      embryos, termed 2-cell embryo-CRISPR-Cas9 injection (2CC), to study the in vivo
      function of essential (or unknown) genes in founder chimeric mice. By injecting
      both Cre mRNA and CRISPR-Cas9 targeting the gene of interest into fluorescent
      reporter mice, the 2CC method can trace both wild-type and mutant cells at
      different developmental stages, offering internal control for phenotypic analyses
      of mutant cells. Using this method, we identified novel functions of the
      essential gene Tet3 in regulating excitatory and inhibitory synaptic transmission
      in the developing mouse cerebral cortex. By generating chimeric mutant mice, the
      2CC method allows for the rapid screening of gene function in multiple tissues
      and cell types in founder chimeric mice, significantly expanding the current
      armamentarium of genetic tools.

PMID- 28429773
TI  - Evaluation of the precision of contrast sensitivity function assessment on a
      tablet device.
AB  - The contrast sensitivity function (CSF) relates the visibility of a spatial
      pattern to both its size and contrast, and is therefore a more comprehensive
      assessment of visual function than acuity, which only determines the smallest
      resolvable pattern size. Because of the additional dimension of contrast,
      estimating the CSF can be more time-consuming. Here, we compare two methods for
      rapid assessment of the CSF that were implemented on a tablet device. For a
      single-trial assessment, we asked 63 myopes and 38 emmetropes to tap the peak of
      a "sweep grating" on the tablet's touch screen. For a more precise assessment,
      subjects performed 50 trials of the quick CSF method in a 10-AFC letter
      recognition task. Tests were performed with and without optical correction, and
      in monocular and binocular conditions; one condition was measured twice to assess
      repeatability. Results show that both methods are highly correlated; using both
      common and novel measures for test-retest repeatability, however, the quick CSF
      delivers more precision with testing times of under three minutes. Further
      analyses show how a population prior can improve convergence rate of the quick
      CSF, and how the multi-dimensional output of the quick CSF can provide greater
      precision than scalar outcome measures.

PMID- 28429774
TI  - Synchronization and variability imbalance underlie cognitive impairment in
      primary-progressive multiple sclerosis.
AB  - We aimed to investigate functional connectivity and variability across multiple
      frequency bands in brain networks underlying cognitive deficits in primary
      progressive multiple sclerosis (PP-MS) and to explore how they are affected by
      the presence of cortical lesions (CLs). We analyzed functional connectivity and
      variability (measured as the standard deviation of BOLD signal amplitude) in
      resting state networks (RSNs) associated with cognitive deficits in different
      frequency bands in 25 PP-MS patients (12 M, mean age 50.9 +/- 10.5 years) and 20
      healthy subjects (9 M, mean age 51.0 +/- 9.8 years). We confirmed the presence of
      a widespread cognitive deterioration in PP-MS patients, with main involvement of
      visuo-spatial and executive domains. Cognitively impaired patients showed
      increased variability, reduced synchronicity between networks involved in the
      control of cognitive macro-domains and hyper-synchronicity limited to the
      connections between networks functionally more segregated. CL volume was higher
      in patients with cognitive impairment and was correlated with functional
      connectivity and variability. We demonstrate, for the first time, that a
      functional reorganization characterized by hypo-synchronicity of functionally
      related/hyper-synchronicity of functionally-segregated large scale networks and
      an abnormal pattern of neural activity underlie cognitive dysfunction in PP-MS,
      and that CLs possibly play a role in variability and functional connectivity
      abnormalities.

PMID- 28429775
TI  - Fucoxanthin provides neuroprotection in models of traumatic brain injury via the
      Nrf2-ARE and Nrf2-autophagy pathways.
AB  - Fucoxanthin is abundant in seaweed and is considered as a powerful antioxidant.
      It has been proposed to possess anti-cancer, anti-obesity and anti-diabetes
      effects. However, its roles in brain injury models have not been fully
      understood. The objective of this study was to investigate the neuroprotection of
      fucoxanthin in models of traumatic brain injury (TBI) and the role of the nuclear
      factor erythroid 2-related factor 2 (Nrf2)-antioxidant-response element (ARE) and
      Nrf2-autophagy pathways in the putative neuroprotection. We found that
      fucoxanthin alleviated TBI-induced secondary brain injury, including neurological
      deficits, cerebral edema, brain lesion and neuronal apoptosis. Moreover, the up
      regulation of malondialdehyde (MDA) and the activity of glutathione peroxidase
      (GPx) were reversed by fucoxanthin treatment. Furthermore, our in vitro studies
      demonstrated that fucoxanthin increased the neuron survival and reduced the
      reactive oxygen species (ROS) level. In addition, fucoxanthin activated the Nrf2
      ARE pathway and autophagy both in vivo and in vitro, which was proven by the
      results of immunohistochemistry, western blot and electrophoretic mobility shift
      assay (EMSA). However, fucoxanthin failed to provide neuroprotection and
      activated autophagy following TBI in Nrf2-/- mice. In conclusion, our studies
      indicated that fucoxanthin provided neuroprotective effects in models of TBI,
      potentially via regulation of the Nrf2-ARE and Nrf2-autophagy pathways.

PMID- 28429776
TI  - Global distribution of particle phase state in atmospheric secondary organic
      aerosols.
AB  - Secondary organic aerosols (SOA) are a large source of uncertainty in our current
      understanding of climate change and air pollution. The phase state of SOA is
      important for quantifying their effects on climate and air quality, but its
      global distribution is poorly characterized. We developed a method to estimate
      glass transition temperatures based on the molar mass and molecular O:C ratio of
      SOA components, and we used the global chemistry climate model EMAC with the
      organic aerosol module ORACLE to predict the phase state of atmospheric SOA. For
      the planetary boundary layer, global simulations indicate that SOA are mostly
      liquid in tropical and polar air with high relative humidity, semi-solid in the
      mid-latitudes and solid over dry lands. We find that in the middle and upper
      troposphere SOA should be mostly in a glassy solid phase state. Thus, slow
      diffusion of water, oxidants and organic molecules could kinetically limit gas
      particle interactions of SOA in the free and upper troposphere, promote ice
      nucleation and facilitate long-range transport of reactive and toxic organic
      pollutants embedded in SOA.

PMID- 28429777
TI  - Interleukin-6 increases the expression and activity of insulin-degrading enzyme.
AB  - Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and
      type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin
      6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE
      expression and activity. IL-6 KO mice displayed lower insulin clearance in the
      liver and skeletal muscle, compared with wild type (WT), due to reduced IDE
      expression and activity. We also observed that after 3-h incubation, IL-6, 50 and
      100 ng ml-1, increased the expression of IDE in HEPG2 and C2C12 cells,
      respectively. In addition, during acute exercise, the inhibition of IL-6
      prevented an increase in insulin clearance and IDE expression and activity,
      mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were
      significantly increased in plasma from humans, after an acute exercise, compared
      to pre-exercise values. Although the increase in plasma IDE activity was only
      marginal, a positive correlation between IL-6 and IDE activity, and between IL-6
      and IDE protein expression, was observed. Our outcomes indicate a novel function
      of IL-6 on the insulin metabolism expanding the possibilities for new potential
      therapeutic strategies, focused on insulin degradation, for the treatment and/or
      prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.

PMID- 28429778
TI  - Reproductive endocrinology: Potential new therapy for hot flushes.

PMID- 28429779
TI  - Metabolism: Adipose and nonadipose effects of FGF21 delineated.

PMID- 28429780
TI  - Insulin analogues in type 1 diabetes mellitus: getting better all the time.
AB  - The treatment of type 1 diabetes mellitus consists of external replacement of the
      functions of beta cells in an attempt to achieve blood levels of glucose as close
      to the normal range as possible. This approach means that glucose sensing needs
      to be replaced and levels of insulin need to mimic physiological insulin-action
      profiles, including basal coverage and changes around meals. Training and
      educating patients are crucial for the achievement of good glycaemic control, but
      having insulin preparations with action profiles that provide stable basal
      insulin coverage and appropriate mealtime insulin peaks helps people with type 1
      diabetes mellitus to live active lives without sacrificing tight glycaemic
      control. Insulin analogues enable patients to achieve this goal, as some have
      fast action profiles, and some have very slow action profiles, which gives people
      with type 1 diabetes mellitus the tools to achieve dynamic insulin-action
      profiles that enable tight glycaemic control with a risk of hypoglycaemia that is
      lower than that with human short-acting and long-acting insulins. This Review
      discusses the established and novel insulin analogues that are used to treat
      patients with type 1 diabetes mellitus and provides insights into the future
      development of insulin analogues.

PMID- 28429781
TI  - Geographic variation in floral traits and the capacity of autonomous selfing
      across allopatric and sympatric populations of two closely related Centaurium
      species.
AB  - Floral traits and the relative contribution of autonomous selfing to total seed
      set varies geographically and is often driven by the availability and abundance
      of suitable pollinators and/or the presence of co-flowering relatives. In the
      latter case, competition for pollinator services and costs of hybridization can
      select for floral traits that reduce interspecific gene flow and contribute to
      prezygotic isolation, potentially leading to geographic variation in floral
      divergence between allopatric and sympatric populations. In this study, we
      investigated variation in floral traits and its implications on the capacity of
      autonomous selfing in both allopatric and sympatric populations of two closely
      related Centaurium species(Gentianaceae) across two distinct geographic
      regions(UK and mainland Europe). Although the magnitude and direction of floral
      differentiation varied between regions, sympatric populations were always
      significantly more divergent in floral traits and the capacity to self
      autonomously than allopatric populations. These results indicate that mating
      systems can vary substantially within a species and that the joint occurrence of
      plant species can have a major impact on floral morphology and capacity of
      autonomous selfing, most likely as a way to reduce the probability of
      interspecific interference.

PMID- 28429782
TI  - Electrochemical generation of sulfur vacancies in the basal plane of MoS2 for
      hydrogen evolution.
AB  - Recently, sulfur (S)-vacancies created on the basal plane of 2H-molybdenum
      disulfide (MoS2) using argon plasma exposure exhibited higher intrinsic activity
      for the electrochemical hydrogen evolution reaction than the edge sites and
      metallic 1T-phase of MoS2 catalysts. However, a more industrially viable
      alternative to the argon plasma desulfurization process is needed. In this work,
      we introduce a scalable route towards generating S-vacancies on the MoS2 basal
      plane using electrochemical desulfurization. Even though sulfur atoms on the
      basal plane are known to be stable and inert, we find that they can be
      electrochemically reduced under accessible applied potentials. This can be done
      on various 2H-MoS2 nanostructures. By changing the applied desulfurization
      potential, the extent of desulfurization and the resulting activity can be
      varied. The resulting active sites are stable under extended desulfurization
      durations and show consistent HER activity.

PMID- 28429783
TI  - Fine structure of the topological defect cores studied for disclinations in
      lyotropic chromonic liquid crystals.
AB  - The detailed structure of singularities of ordered field represents a fundamental
      problem in diverse areas of physics. At the defect cores, the deformations are so
      strong that the system explores states with symmetry different from that of an
      undistorted material. These regions are difficult to explore experimentally as
      their spatial extension is very small, a few molecular lengths in the condensed
      matter. Here we explore the cores of disclinations in the so-called chromonic
      nematics that extend over macroscopic length scales accessible for optical
      characterization. We demonstrate that the amplitude S and the phase (the
      director) of the order parameter vary along both the radial and azimuthal
      directions, in contrast to the classic models in which S varies only with the
      distance from the centre and depends only on the azimuthal coordinate. This
      unexpected core structure is explained by a strong coupling of the phase and
      amplitude of the order parameter in the free energy.

PMID- 28429784
TI  - Sight and sound persistently out of synch: stable individual differences in
      audiovisual synchronisation revealed by implicit measures of lip-voice
      integration.
AB  - Are sight and sound out of synch? Signs that they are have been dismissed for
      over two centuries as an artefact of attentional and response bias, to which
      traditional subjective methods are prone. To avoid such biases, we measured
      performance on objective tasks that depend implicitly on achieving good lip
      synch. We measured the McGurk effect (in which incongruent lip-voice pairs evoke
      illusory phonemes), and also identification of degraded speech, while
      manipulating audiovisual asynchrony. Peak performance was found at an average
      auditory lag of ~100 ms, but this varied widely between individuals.
      Participants' individual optimal asynchronies showed trait-like stability when
      the same task was re-tested one week later, but measures based on different tasks
      did not correlate. This discounts the possible influence of common biasing
      factors, suggesting instead that our different tasks probe different brain
      networks, each subject to their own intrinsic auditory and visual processing
      latencies. Our findings call for renewed interest in the biological causes and
      cognitive consequences of individual sensory asynchronies, leading potentially to
      fresh insights into the neural representation of sensory timing. A concrete
      implication is that speech comprehension might be enhanced, by first measuring
      each individual's optimal asynchrony and then applying a compensatory auditory
      delay.

PMID- 28429785
TI  - Natriuretic peptide receptor guanylyl cyclase-A pathway counteracts glomerular
      injury evoked by aldosterone through p38 mitogen-activated protein kinase
      inhibition.
AB  - Guanylyl cyclase-A (GC-A) signaling, a natriuretic peptide receptor, exerts
      renoprotective effects by stimulating natriuresis and reducing blood pressure.
      Previously we demonstrated massive albuminuria with hypertension in
      uninephrectomized, aldosterone-infused, and high salt-fed (ALDO) systemic GC-A KO
      mice with enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK)
      in podocytes. In the present study, we examined the interaction between p38 MAPK
      and GC-A signaling. The administration of FR167653, p38 MAPK inhibitor, reduced
      systolic blood pressure (SBP), urinary albumin excretion, segmental sclerosis,
      podocyte injury, and apoptosis. To further investigate the local action of
      natriuretic peptide and p38 MAPK in podocytes, we generated podocyte-specific
      (pod) GC-A conditional KO (cKO) mice. ALDO pod GC-A cKO mice demonstrated
      increased urinary albumin excretion with marked mesangial expansion, podocyte
      injury and apoptosis, but without blood pressure elevation. FR167653 also
      suppressed urinary albumin excretion without reducing SBP. Finally, we revealed
      that atrial natriuretic peptide increased phosphorylation of MAPK phosphatase-1
      (MKP-1) concomitant with inhibited phosphorylation of p38 MAPK in response to
      MAPK kinase 3 activation, thereby resulting in decreased mRNA expression of the
      apoptosis-related gene, Bax, and Bax/Bcl2 ratio in cultured podocytes. These
      results indicate that natriuretic peptide exerts a renoprotective effect via
      inhibiting phosphorylation of p38 MAPK in podocytes.

PMID- 28429786
TI  - Comprehensive assessment showed no associations of variants at the SLC10A1 locus
      with susceptibility to persistent HBV infection among Southern Chinese.
AB  - The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was
      recently demonstrated to be a functional receptor for hepatitis B virus (HBV).
      The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651)
      in exon 4, has been frequently investigated in regard to risk of persistent HBV
      infection. However, these investigations have generated conflicting results. To
      examine whether common genetic variation at the SLC10A1 locus is associated with
      risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide
      polymorphisms (SNPs) were assessed in two case-control sample sets, totally
      including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124
      controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry. To
      test whether rare or subpolymorphic SLC10A1 variants are associated with disease
      risk, the gene's exons in 244 cases were sequenced. Overall, we found neither
      SNPs nor haplotypes of SLC10A1 showed significant association in the two sample
      sets. Furthermore, no significant associations of rare variants or copy number
      variation covering SLC10A1 were observed. Finally, expression quantitative trait
      locus analyses revealed that SNPs potentially affecting SLC10A1 expression also
      showed no significant associations. We conclude that genetic variation at the
      SLC10A1 locus is not likely a major risk factor of persistent HBV infection among
      Southern Chinese.

PMID- 28429787
TI  - Heat, temperature and Clausius inequality in a model for active Brownian
      particles.
AB  - Methods of stochastic thermodynamics and hydrodynamics are applied to a recently
      introduced model of active particles. The model consists of an overdamped
      particle subject to Gaussian coloured noise. Inspired by stochastic
      thermodynamics, we derive from the system's Fokker-Planck equation the average
      exchanges of heat and work with the active bath and the associated entropy
      production. We show that a Clausius inequality holds, with the local (non
      uniform) temperature of the active bath replacing the uniform temperature usually
      encountered in equilibrium systems. Furthermore, by restricting the dynamical
      space to the first velocity moments of the local distribution function we derive
      a hydrodynamic description where local pressure, kinetic temperature and internal
      heat fluxes appear and are consistent with the previous thermodynamic analysis.
      The procedure also shows under which conditions one obtains the unified coloured
      noise approximation (UCNA): such an approximation neglects the fast relaxation to
      the active bath and therefore yields detailed balance and zero entropy
      production. In the last part, by using multiple time-scale analysis, we provide a
      constructive method (alternative to UCNA) to determine the solution of the
      Kramers equation and go beyond the detailed balance condition determining
      negative entropy production.

PMID- 28429789
TI  - Cell death: ESCRTing dying cells back to life.

PMID- 28429790
TI  - Ageing: Is fat a key to longevity?

PMID- 28429788
TI  - The HSP90 chaperone machinery.
AB  - The heat shock protein 90 (HSP90) chaperone machinery is a key regulator of
      proteostasis under both physiological and stress conditions in eukaryotic cells.
      As HSP90 has several hundred protein substrates (or 'clients'), it is involved in
      many cellular processes beyond protein folding, which include DNA repair,
      development, the immune response and neurodegenerative disease. A large number of
      co-chaperones interact with HSP90 and regulate the ATPase-associated
      conformational changes of the HSP90 dimer that occur during the processing of
      clients. Recent progress has allowed the interactions of clients with HSP90 and
      its co-chaperones to be defined. Owing to the importance of HSP90 in the
      regulation of many cellular proteins, it has become a promising drug target for
      the treatment of several diseases, which include cancer and diseases associated
      with protein misfolding.

PMID- 28429791
TI  - Social and anthropometric factors explaining racial/ethnical differences in birth
      weight in the United States.
AB  - Though disparities in birth weight by race/ethnicity have been extensively
      reported in the United States, few studies have systematically investigated
      factors attributing to its variability. For 10,638,415 singleton infants born
      during 2009-2012 in the United States, we examined birth weight differences among
      14 races and ethnicities (non-Hispanic white, non-Hispanic Black, American
      Indian, Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Hawaiian,
      Guamanian, Mexican, Puerto Rican and Cuban), after sequentially adjusting for
      maternal, socio-economic and behavioral factors. Average birthweight of non
      Hispanic white infants was 3381 g, while for other races/ethnicities birth weight
      ranged from being 289 g smaller in Japanese to 126 g larger in Samoan infants.
      Factors explaining differences of more than 50 grams in birth weight compared to
      white infants were: gestational age for black infants, height and body mass index
      for all Asian and Samoan mothers, and gestational weight gain for Japanese
      mothers. Difference in maternal age, parity, socioeconomic and behavioral
      characteristics did not account for significant portion of birthweight variations
      for any race. Our findings suggest that differences in maternal anthropometrics,
      gestational weight gain, and preterm birth rate, but not in maternal age, parity,
      socioeconomic or behavioral characteristics contribute to racial/ethnic
      differences in birthweight.

PMID- 28429792
TI  - Nutrient removal from Chinese coastal waters by large-scale seaweed aquaculture.
AB  - China is facing intense coastal eutrophication. Large-scale seaweed aquaculture
      in China is popular, now accounting for over 2/3's of global production. Here, we
      estimate the nutrient removal capability of large-scale Chinese seaweed farms to
      determine its significance in mitigating eutrophication. We combined estimates of
      yield and nutrient concentration of Chinese seaweed aquaculture to quantify that
      one hectare of seaweed aquaculture removes the equivalent nutrient inputs
      entering 17.8 ha for nitrogen and 126.7 ha for phosphorus of Chinese coastal
      waters, respectively. Chinese seaweed aquaculture annually removes approximately
      75,000 t nitrogen and 9,500 t phosphorus. Whereas removal of the total N inputs
      to Chinese coastal waters requires a seaweed farming area 17 times larger than
      the extant area, one and a half times more of the seaweed area would be able to
      remove close to 100% of the P inputs. With the current growth rate of seaweed
      aquaculture, we project this industry will remove 100% of the current phosphorus
      inputs to Chinese coastal waters by 2026. Hence, seaweed aquaculture already
      plays a hitherto unrealized role in mitigating coastal eutrophication, a role
      that may be greatly expanded with future growth of seaweed aquaculture.

PMID- 28429793
TI  - Attogram mass sensing based on silicon microbeam resonators.
AB  - Using doubly-clamped silicon (Si) microbeam resonators, we demonstrate sub
      attogram per Hertz (ag/Hz) mass sensitivity, which is extremely high sensitivity
      achieved by micro-scale MEMS mass sensors. We also characterize unusual buckling
      phenomena of the resonators. The thin-film based resonator is composed of a Si
      microbeam surrounded by silicon nitride (SiN) anchors, which significantly
      improve performance by providing fixation on the microbeam and stabilizing
      oscillating motion. Here, we introduce two fabrication techniques to further
      improve the mass sensitivity. First, we minimize surface stress by depositing a
      sacrificial SiN layer, which prevents damage on the Si microbeam. Second, we
      modify anchor structure to find optimal design that allows the microbeam to
      oscillate in quasi-one dimensional mode while achieving high quality factor. Mass
      loading is conducted by depositing Au/Ti thin films on the local area of the
      microbeam surface. Using sequential mass loading, we test effects of changing
      beam dimensions, position of mass loading, and distribution of a metal film on
      the mass sensitivity. In addition, we demonstrate that microbeams suffer local
      micro-buckling and global buckling by excessive mass loading, which are induced
      by two different mechanisms. We also find that the critical buckling length is
      increased by additional support from the anchors.

PMID- 28429795
TI  - CD200-positive cancer associated fibroblasts augment the sensitivity of Epidermal
      Growth Factor Receptor mutation-positive lung adenocarcinomas to EGFR Tyrosine
      kinase inhibitors.
AB  - Cancer associated fibroblasts (CAFs) play important roles in the chemotherapeutic
      process, especially through influencing the resistance of tumor cells to
      molecular targeted therapy. Here we report the existence of a special
      subpopulation of patient-specific-CAFs that augment the sensitivity of EGFR gene
      mutation-positive lung cancer to the EGFR-tyrosine kinase inhibitor (EGFR-TKI),
      gefitinib. When cocultured with EGFR mutation positive lung cancer cells, these
      CAFs increased the apoptic effect of gefitinib on cancer cells, whereas, in the
      absence of gefitinib, they did not affect cancer cell viability. The assay using
      different single cell-derived clones demonstrated that the aforementioned
      sensitizing ability is clone-specific. Microarray analysis revealed that CD200
      was expressed at much higher levels in this CAFs. Knocking down of CD200
      expression deprived CAFs of their sensitizing potential, suggesting that CD200 is
      the functional molecule responsible for the effect. Immunohistochemical analysis
      of samples from patients receiving postoperative gefitinib treatment revealed
      that the individuals whose resected lung adenocarcinomas contained CD200-positive
      CAFs tended to have longer progression free survival of gefitinib when they
      recurred after surgery. These results suggest that CD200-positive CAFs can
      augment the sensitivity to EGFR-TKIs and may possess far reaching applications in
      the therapeutic use of EGFR-TKIs.

PMID- 28429796
TI  - Spatial Control of Functional Response in 4D-Printed Active Metallic Structures.
AB  - We demonstrate a method to achieve local control of 3-dimensional thermal history
      in a metallic alloy, which resulted in designed spatial variations in its
      functional response. A nickel-titanium shape memory alloy part was created with
      multiple shape-recovery stages activated at different temperatures using the
      selective laser melting technique. The multi-stage transformation originates from
      differences in thermal history, and thus the precipitate structure, at various
      locations created from controlled variations in the hatch distance within the
      same part. This is a first example of precision location-dependent control of
      thermal history in alloys beyond the surface, and utilizes additive manufacturing
      techniques as a tool to create materials with novel functional response that is
      difficult to achieve through conventional methods.

PMID- 28429794
TI  - Bone-in-culture array as a platform to model early-stage bone metastases and
      discover anti-metastasis therapies.
AB  - The majority of breast cancer models for drug discovery are based on orthotopic
      or subcutaneous tumours. Therapeutic responses of metastases, especially
      microscopic metastases, are likely to differ from these tumours due to distinct
      cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such
      differences, we established an ex vivo bone metastasis model, termed bone-in
      culture array or BICA, by fragmenting mouse bones preloaded with breast cancer
      cells via intra-iliac artery injection. Cancer cells in BICA maintain features of
      in vivo bone micrometastases regarding the microenvironmental niche, gene
      expression profile, metastatic growth kinetics and therapeutic responses. Through
      a proof-of-principle drug screening using BICA, we found that danusertib, an
      inhibitor of the Aurora kinase family, preferentially inhibits bone
      micrometastases. In contrast, certain histone methyltransferase inhibitors
      stimulate metastatic outgrowth of indolent cancer cells, specifically in the
      bone. Thus, BICA can be used to investigate mechanisms involved in bone
      colonization and to rapidly test drug efficacies on bone micrometastases.

PMID- 28429797
TI  - Sirtuins in the phylum Basidiomycota: A role in virulence in Cryptococcus
      neoformans.
AB  - Virulence of Cryptococcus neoformans is regulated by a range of transcription
      factors, and is also influenced by the acquisition of adaptive mutations during
      infection. Beyond the temporal regulation of virulence factor production by
      transcription factors and these permanent microevolutionary changes, heritable
      epigenetic modifications such as histone deacetylation may also play a role
      during infection. Here we describe the first comprehensive analysis of the
      sirtuin class of NAD+ dependent histone deacetylases in the phylum Basidiomycota,
      identifying five sirtuins encoded in the C. neoformans genome. Each sirtuin gene
      was deleted and a wide range of phenotypic tests performed to gain insight into
      the potential roles they play. Given the pleiotropic nature of sirtuins in other
      species, it was surprising that only two of the five deletion strains revealed
      mutant phenotypes in vitro. However, cryptic consequences of the loss of each
      sirtuin were identified through whole cell proteomics, and mouse infections
      revealed a role in virulence for SIR2, HST3 and HST4. The most intriguing
      phenotype was the repeated inability to complement mutant phenotypes through the
      reintroduction of the wild-type gene. These data support the model that
      regulation of sirtuin activity may be employed to enable a drastic alteration of
      the epigenetic landscape and virulence of C. neoformans.

PMID- 28429798
TI  - Sensory system plasticity in a visually specialized, nocturnal spider.
AB  - The interplay between an animal's environmental niche and its behavior can
      influence the evolutionary form and function of its sensory systems. While
      intraspecific variation in sensory systems has been documented across distant
      taxa, fewer studies have investigated how changes in behavior might relate to
      plasticity in sensory systems across developmental time. To investigate the
      relationships among behavior, peripheral sensory structures, and central
      processing regions in the brain, we take advantage of a dramatic within-species
      shift of behavior in a nocturnal, net-casting spider (Deinopis spinosa), where
      males cease visually-mediated foraging upon maturation. We compared eye diameters
      and brain region volumes across sex and life stage, the latter through micro
      computed X-ray tomography. We show that mature males possess altered peripheral
      visual morphology when compared to their juvenile counterparts, as well as
      juvenile and mature females. Matching peripheral sensory structure modifications,
      we uncovered differences in relative investment in both lower-order and higher
      order processing regions in the brain responsible for visual processing. Our
      study provides evidence for sensory system plasticity when individuals
      dramatically change behavior across life stages, uncovering new avenues of
      inquiry focusing on altered reliance of specific sensory information when
      entering a new behavioral niche.

PMID- 28429799
TI  - Expression control of the AMPK regulatory subunit and its functional significance
      in yeast ER stress response.
AB  - AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimeric
      kinase complex consisting of a catalytic subunit, alpha, and two regulatory
      subunits, beta and gamma. Previously, we demonstrated that Snf1, the
      Saccharomyces cerevisiae ortholog of AMPK, negatively regulates the unfolded
      protein response (UPR) pathway and the Hog1 MAP kinase pathway in ER stress
      response. However, it remains unclear how the alternate three beta subunits,
      Sip1, Sip2, and Gal83, of the Snf1 complex participate in ER stress response.
      Here, we show that Gal83 plays a major role in Snf1-mediated downregulation of
      the UPR and Hog1 pathways. Gal83 is the most abundant beta subunit in the normal
      state and further induced by ER stress. This induction is mediated via activation
      of the GAL83 promoter by the UPR. When expressed under the control of the GAL83
      promoter, Sip2 exhibits potent functional activity equivalent to Gal83. Our
      results suggest that the functional significance of the beta subunit of Snf1 AMPK
      in ER stress response is defined by modulation of the expression level through
      regulation of the promoter activity.

PMID- 28429800
TI  - Straight and rigid flagellar hook made by insertion of the FlgG specific sequence
      into FlgE.
AB  - The bacterial flagellar hook connects the helical flagellar filament to the
      rotary motor at its base. Bending flexibility of the hook allows the helical
      filaments to form a bundle behind the cell body to produce thrust for bacterial
      motility. The hook protein FlgE shows considerable sequence and structural
      similarities to the distal rod protein FlgG; however, the hook is supercoiled and
      flexible as a universal joint whereas the rod is straight and rigid as a drive
      shaft. A short FlgG specific sequence (GSS) has been postulated to confer the
      rigidity on the FlgG rod, and insertion of GSS at the position between Phe-42 and
      Ala-43 of FlgE actually made the hook straight. However, it remains unclear
      whether inserted GSS confers the rigidity as well. Here, we provide evidence that
      insertion of GSS makes the hook much more rigid. The GSS insertion inhibited
      flagellar bundle formation behind the cell body, thereby reducing motility. This
      indicates that the GSS insertion markedly reduced the bending flexibility of the
      hook. Therefore, we propose that the inserted GSS makes axial packing
      interactions of FlgE subunits much tighter in the hook to suppress axial
      compression and extension of the protofilaments required for bending flexibility.

PMID- 28429802
TI  - Parkinson disease: In situ astrocyte reprogramming - simpler cell replacement
      therapy in PD?

PMID- 28429803
TI  - Observational studies and the chicken and egg issue in stroke.

PMID- 28429801
TI  - The dizzy patient: don't forget disorders of the central vestibular system.
AB  - Vertigo and dizziness are among the most common complaints in neurology clinics,
      and they account for about 13% of the patients entering emergency units. In this
      Review, we focus on central vestibular disorders, which are mostly attributable
      to acute unilateral lesions of the bilateral vestibular circuitry in the brain.
      In a tertiary interdisciplinary outpatient dizziness unit, central vestibular
      disorders, including vestibular migraine, comprise about 25% of the established
      diagnoses. The signs and symptoms of these disorders can mimic those of
      peripheral vestibular disorders with sustained rotational vertigo. Bedside
      examinations, such as the head impulse test and ocular motor testing to determine
      spontaneous and gaze-evoked nystagmus or skew deviation, reliably differentiate
      central from peripheral syndromes. We also consider disorders of 'higher
      vestibular functions', which involve more than one sensory modality as well as
      cognitive domains (for example, orientation, spatial memory and navigation).
      These disorders include hemispatial neglect, the room tilt illusion, pusher
      syndrome, and impairment of spatial memory and navigation associated with
      hippocampal atrophy in cases of peripheral bilateral vestibular loss.

PMID- 28429805
TI  - Bio-inspired, large scale, highly-scattering films for nanoparticle-alternative
      white surfaces.
AB  - Inspired by the white beetle of the genus Cyphochilus, we fabricate ultra-thin,
      porous PMMA films by foaming with CO2 saturation. Optimising pore diameter and
      fraction in terms of broad-band reflectance results in very thin films with
      exceptional whiteness. Already films with 60 um-thick scattering layer feature a
      whiteness with a reflectance of 90%. Even 9 um thin scattering layers appear
      white with a reflectance above 57%. The transport mean free path in the
      artificial films is between 3.5 um and 4 um being close to the evolutionary
      optimised natural prototype. The bio-inspired white films do not lose their
      whiteness during further shaping, allowing for various applications.

PMID- 28429806
TI  - Control of structural transition in FeSe1-xTex thin films by changing substrate
      materials.
AB  - Iron chalcogenide superconductors FeSe1-xTex are important materials for
      investigating the relation be-tween the superconductivity and the orbital and/or
      electronic nematic order, because the end member material FeSe exhibits a
      structural transition without a magnetic phase transition. However, the phase
      separation occurs in the region of 0.1 <= x <= 0.4 for bulk samples, and it
      prevents the complete understanding of this system. Here, we report the
      successful fabrication of epitaxial thin films of FeSe1-xTex with 0 <= x <= 0.7,
      which includes the phase-separation region, on LaAlO3 substrates via pulsed laser
      deposition. In the temperature dependences of differential resistivity for these
      films with 0 <= x <= 0.3, the dip- or peak- anomalies, which are well-known to be
      originated from the structural transition in FeSebulk samples, are observed at
      the characteristic temperatures, T*. The doping-temperature (x-T) phase diagram
      of FeSe1-xTex films clearly shows that T* decreases with increasing x, and that
      Tc suddenly changes at a certain Te content where T* disappears, which turns out
      to be commonly observed for both films on LaAlO3 and CaF2. These indicate the
      importance of controlling the structural transition to achieve high Tc in iron
      chalcogenides.

PMID- 28429807
TI  - Prediction of a new BeC monolayer with perfectly planar tetracoordinate carbons.
AB  - Recently, there has been a growing interest in exploring planar hypercoordinate
      carbons in two-dimensional nanostructures. However, atomic monolayers with ideal
      planar hypercoordinate carbon are quite rare due to the challenge in stabilizing
      the exotic motifs. We predicted a global minimum two-dimensional BeC monolayer
      using the global particle-swarm optimization method. Each carbon binds peripheral
      four atoms in the same plane, forming a perfectly planar tetracoordinate carbon
      moiety. The cohesive energy, phonon-spectrum and mechanical stability criteria
      confirm the stability of monolayer BeC. In addition, the BeC monolayer has a
      large in-plane stiffness (145.54 N m-1) and thermo-dynamical stability (up to
      2000 K). Furthermore, BeC is an indirect semiconductor with a band gap of 1.01 eV
      and possesses exceptionally high carrier mobilities (~104 cm2 V-1 s-1), rendering
      it suitable for application in electronics and photoelectronics.

PMID- 28429808
TI  - Slow creep in soft granular packings.
AB  - Transient creep mechanisms in soft granular packings are studied numerically
      using a constant pressure and constant stress simulation method. Rapid
      compression followed by slow dilation is predicted on the basis of a logarithmic
      creep phenomenon. Characteristic scales of creep strain and time exhibit a power
      law dependence on jamming pressure, and they diverge at the jamming point.
      Microscopic analysis indicates the existence of a correlation between rheology
      and nonaffine fluctuations. Localized regions of large strain appear during creep
      and grow in magnitude and size at short times. At long times, the spatial
      structure of highly correlated local deformation becomes time-invariant. Finally,
      a microscale connection between local rheology and local fluctuations is
      demonstrated in the form of a linear scaling between granular fluidity and
      nonaffine velocity.

PMID- 28429804
TI  - Identifying tagging SNPs for African specific genetic variation from the African
      Diaspora Genome.
AB  - A primary goal of The Consortium on Asthma among African-ancestry Populations in
      the Americas (CAAPA) is to develop an 'African Diaspora Power Chip' (ADPC), a
      genotyping array consisting of tagging SNPs, useful in comprehensively
      identifying African specific genetic variation. This array is designed based on
      the novel variation identified in 642 CAAPA samples of African ancestry with high
      coverage whole genome sequence data (~30* depth). This novel variation extends
      the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing
      Projects to a spectrum of populations representing the wide range of West African
      genomic diversity. These individuals from CAAPA also comprise a large swath of
      the African Diaspora population and incorporate historical genetic diversity
      covering nearly the entire Atlantic coast of the Americas. Here we show the
      results of designing and producing such a microchip array. This novel array
      covers African specific variation far better than other commercially available
      arrays, and will enable better GWAS analyses for researchers with individuals of
      African descent in their study populations. A recent study cataloging variation
      in continental African populations suggests this type of African-specific
      genotyping array is both necessary and valuable for facilitating large-scale GWAS
      in populations of African ancestry.

PMID- 28429809
TI  - Successful PEGylation of hollow encapsulin nanoparticles from Rhodococcus
      erythropolis N771 without affecting their disassembly and reassembly properties.
AB  - We developed a hollow PEGylated encapsulin nanoparticle from Rhodococcus
      erythropolis N771. The hollow engineered encapsulin nanoparticles with His-Tag
      and Lys residues on the surface were constructed by means of genetic
      recombination. The Lys residues on the particle surface were successfully
      PEGylated with a PEG derivative, methoxy-PEG-SCM. Consequently, we demonstrated
      that the hollow PEGylated engineered encapsulin nanoparticle could successfully
      disassemble or reassemble even after PEGylation in the presence or absence of a
      protein denaturing agent. The nanoparticle obtained in the present study has the
      potential to incorporate hydrophilic compounds in the internal cavity of the
      particle by reversibly controllable disassembly and reassembly. The hollow
      PEGylated encapsulin nanoparticle can be used as a drug carrier for the delivery
      of hydrophilic biopolymers in future medical applications.

PMID- 28429811
TI  - Synthesis and structural characterisation of the aggregates of benzo-1,2
      chalcogenazole 2-oxides.
AB  - Iodine oxidation of bis[2-(hydroxyiminomethyl)phenyl] dichalcogenides yields
      benzo-1,2-chalcogenazole 2-oxides. Annulated derivatives of iso-tellurazole N
      oxides spontaneously aggregate into cyclic tetra- and hexamers through TeO
      chalcogen bonding; the structures of the co-crystals with benzene and CH2Cl2
      illustrate the ability of these macrocycles to interact with small guest
      molecules. The selenium congener crystallizes forming a supramolecular polymer.
      VT NMR indicates that both compounds aggregate in solution but only at low
      temperature in the selenium case. The different abilities of these molecules to
      engage in supramolecular interactions are interpreted on the basis of their
      electronic properties evaluated with DFT-D3 calculations.

PMID- 28429810
TI  - Cisplatin-directed coordination-crosslinking nanogels with thermo/pH-sensitive
      triblock polymers: improvement on chemotherapic efficacy via sustained release
      and drug retention.
AB  - To realize the sustained release and long-term intratumoural retention of water
      soluble cisplatin, thermo/pH-sensitive cisplatin-directed coordination
      crosslinking nanogels (Pt-PNA) were developed via the coordination bonds of Pt
      carboxyl groups. As the coordination ratio (CR) of the Pt-carboxyl bonds
      increased from 5% to 35%, the sizes of the Pt-PNA nanogels decreased from 999 nm
      to 167 nm, and their zeta potentials increased from -35 mV to -13 mV. Only
      through a simple mixing of cisplatin and PNAs, the entrapment efficiencies (EEs)
      of the Pt-PNA nanogels reached near 100% (>90%), and the drug-loading amounts
      (DLs) of cisplatin could achieve up to 25.5 +/- 0.1%. For water-soluble
      cisplatin, Pt-PNA nanogels exhibited a sustained release for as long as 5 days.
      The thermo/pH-sensitive sol-gel phase-transition behaviour of the Pt-PNA nanogels
      were investigated via inverting-vial and rheological methods. Platinum elemental
      analysis indicated that the Pt-PNA nanogels showed a much stronger ability of
      cisplatin retention in tumours than free cisplatin. The platinum content in a
      tumour treated by the Pt-PNA nanogels was far higher than that by free cisplatin:
      200.7 +/- 63.6 MUg vs. 82.7 +/- 26.8 MUg at the 1st day, or 118.9 +/- 35.2 MUg
      vs. 18.5 +/- 9.4 MUg at the 14th day. The evaluation of the in vivo antitumour
      efficacy indicated that only after a single dose of Pt-PNA nanogels, the tumour
      volume continuously decreased to 0.73 +/- 0.07 times that of the original tumour
      volume (OTV) for 14 days; however, it rapidly increased by 3.37 +/- 0.82, 8.01 +/
      0.53 and 9.25 +/- 1.85 times that of the OTV with the same dose of free
      cisplatin, PNA, and NS, respectively. Some preliminary evaluations of the
      biocompatibility indicated that the toxic side effects of cisplatin could be
      greatly improved via cisplatin-directed coordination-crosslinking with PNA. As a
      result, Pt-PNA nanogels could likely become a promising versatile strategy for
      improving antitumour efficacy and reducing the toxicity and size effects of
      platinum-based drugs, and they could also be developed as promising nanomedicines
      for regional chemotherapy.

PMID- 28429812
TI  - Hollow hematite single crystals deposited with ultra-thin Al2O3 by atom layer
      deposition for improved photoelectrochemical performance.
AB  - Hematite (alpha-Fe2O3) is a red material with a band gap of about 2.0 eV, which
      indicates that it can absorb more solar light. It is a promising photocatalyst
      applied in many fields. In this paper, alpha-Fe2O3 single crystal hollow
      hexagonal bipyramids were synthesized by a simple one-pot hydrothermal method.
      The morphology and structure of the prepared alpha-Fe2O3 hollow hexagonal
      bipyramids were studied using scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), and X-ray diffraction (XRD). The hollow single
      crystals show a good light absorption and performance in photodegradation of
      methylene blue (MB). Due to the strategy of depositing ultra-thin layers of Al2O3
      by atomic layer deposition (ALD), the photoelectrochemical (PEC) performance of
      alpha-Fe2O3 under the simulated solar light irradiation is also improved.

PMID- 28429813
TI  - Rh-catalyzed direct arylation of a polyhedral oligomeric silsesquioxane.
AB  - The electronic properties of polyhedral oligomeric silsesquioxanes (POSS) have
      recently been subjected to study. Although theoretical calculations have
      predicted that POSS can work as an acceptor for pi-conjugated organic units, an
      effective reaction to incorporate aryl groups into a POSS backbone remains to be
      established. In this work, Rh-catalyzed direct arylation has been developed.
      Heptaisobutyl-POSS with a Si-H group was reacted with various aryl halides to
      form aryl-substitued POSSs.

PMID- 28429814
TI  - Sulfated polysaccharides from Enteromorpha prolifera suppress SREBP-2 and HMG-CoA
      reductase expression and attenuate non-alcoholic fatty liver disease induced by a
      high-fat diet.
AB  - Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is
      associated with abnormal cholesterol metabolism. Previous work indicates that
      polysaccharides from alga Enteromorpha prolifera improve glucose metabolism and
      lower cholesterol in diabetic rats. Thus, we studied the possible protective
      effects of E. prolifera polysaccharides (EP) in the development of NAFLD and
      underlying mechanisms. EP (200 mg kg-1) significantly reduced the liver weight
      and significantly lowered hepatic HMG-CoA reductase (HMGCR) mRNA protein
      expression. EP suppressed sterol regulatory element binding protein-2, which is a
      key transcription factor in cholesterol metabolism and regulates the expression
      of HMGCR. Therefore, EP may be a functional food that can prevent NAFLD.

PMID- 28429815
TI  - Cancer vaccination causes prolonged FDG accumulation in subcutaneous tissue.

PMID- 28429816
TI  - A randomised controlled trial to test the effect of promoting caregiver
      contingent talk on language development in infants from diverse socioeconomic
      status backgrounds.
AB  - BACKGROUND: Early language skills are critical for later academic success. Lower
      socioeconomic status (SES) children tend to start school with limited language
      skills compared to advantaged peers. We test the hypothesis that this is due in
      part to differences in caregiver contingent talk during infancy (how often the
      caregiver talks about what is in the focus of the infant's attention). METHODS:
      In a randomised controlled trial with high and low SES families, 142 11-month
      olds and their caregivers were randomly allocated to either a contingent talk
      intervention or a dental health control. Families in the language intervention
      watched a video about contingent talk and were asked to practise it for 15 min a
      day for a month. Caregiver communication was assessed at baseline and after 1
      month. Infant communication was assessed at baseline, 12, 15, 18 and 24 months.
      RESULTS: At baseline, social gradients were observed in caregiver contingent talk
      to their 11-month olds (but not in infant communication). At posttest, when
      infants were 12 months old, caregivers across the SES spectrum who had been
      allocated to the language intervention group engaged in significantly more
      contingent talk. Lower SES caregivers in this intervention group also reported
      that their children produced significantly more words at 15 and 18 months.
      Effects of the intervention did not persist at 24 months. Instead expressive
      vocabulary at this age was best predicted by baseline infant communication,
      baseline contingent talk and SES. CONCLUSIONS: A social gradient in children's
      communication emerges during the second year of life. A low-intensity
      intervention demonstrated that it is possible to increase caregiver contingent
      talk and that this is effective in promoting vocabulary growth for lower SES
      infants in the short term. However, these effects are not long-lasting,
      suggesting that follow-up interventions may be necessary to yield benefits
      lasting to school entry.

PMID- 28429817
TI  - Investigation of bacterial viability from incubated saliva by application of flow
      cytometry and hyphenated separation techniques.
AB  - The aim of the study was determination of bacterial viability in saliva samples
      and finding a correlation between microbiological and volatile profiles of saliva
      depending on incubation time. Bacteria colonizing healthy oral cavities were also
      identified. Twelve healthy adults donated unstimulated saliva samples. Flow
      cytometry, optical density measurements and colony-forming unit (CFU) counting
      method were employed for analyses of native and inoculated saliva after 0, 1, 2,
      24, and 48 h of incubation. Volatile profiles were acquired using headspace-solid
      phase microextraction-gas chromatography/mass spectrometry (HS-SPME-GC/MS). Oral
      bacteria were the most viable within 2 h after collection of saliva. Extension of
      incubation time to 48 h caused considerable decrease in live bacteria counts and
      sharp increase in dead bacteria counts. The most prevalent strain was
      Sphingomonas paucimobilis (26.67%). The number of volatiles raised from 5 to 27
      with incubation time and most of them were putrefaction products, such as
      methanethiol, indole and pyrrole. HS-SPME-GC/MS method is insufficient for
      volatile profiling of "fresh" saliva and should be directed rather to
      investigation of bacterial metabolites.

PMID- 28429818
TI  - Piscirickettsia salmonis infection in cultured lumpfish (Cyclopterus lumpus L.).
AB  - A Piscirickettsia salmonis infection was diagnosed in lumpfish (Cyclopterus
      lumpus L.) juveniles held in a marine research facility on the west coast of
      Ireland. The main clinical signs and pathology included marked ascites, severe
      multifocal liver necrosis and severe diffuse inflammation and necrosis of the
      exocrine pancreas and peri-pancreatic adipose tissue. Numerous Piscirickettsia
      like organisms were observed by histopathology in the affected organs, and the
      bacterial species was characterized by molecular analysis. Sequencing of the
      partial 16S rDNA gene and internal transcribed spacer region showed the lumpfish
      sequences to be closely related to previously identified Atlantic salmon (Salmo
      salar L.) sequences from Ireland. To the authors' knowledge, this is the first
      detection of P. salmonis in lumpfish worldwide. The infection is considered
      potentially significant in terms of lumpfish health and biosecurity.

PMID- 28429819
TI  - Effects of dielectrophoresis on thrombogenesis in human whole blood.
AB  - Thrombogenesis (blood clot formation) is a major barrier to the development of
      biomedical devices that interface with blood. Although state-of-the-art
      chemically and pharmacologically mediated clot mitigation strategies are
      effective, some limitations of such approaches include depletion of active
      agents, or adverse reactions in patients. Increased clotting protein adsorption
      and platelet adhesion, which occur when artificial surfaces are exposed to blood
      result in enhanced clot formation on artificial surfaces. It is hypothesized that
      repelling proteins and platelets using dielectrophoresis (DEP), a contact-free
      particle manipulation technique, will reduce clot formation in biomedical
      devices. In this paper, the effect of DEP on thrombogenesis in human blood is
      investigated. Undiluted whole blood from human donors is pumped through
      microchannels at a physiological shear rate (400 s-1 ). Experiments are performed
      by applying 0 V, 0.5 Vrms , 2 Vrms , and 3 Vrms to electrodes in the channel.
      Clot formation is observed to decrease in experiments in which DEP electrodes are
      active (average of 6% coverage @ 0V reduced to 0.08% coverage @ 3 Vrms ).
      Repulsion is more effective at higher voltages. DEP causes a quantifiable
      reduction in microscopic and macroscopic clot formation in PDMS microchannels.

PMID- 28429820
TI  - Clinical bandings of Patient-Oriented Eczema Measure scores among Japanese
      patients with atopic eczema.

PMID- 28429821
TI  - Dating violence is an important issue in nursing education.

PMID- 28429822
TI  - What goes around comes around: an investigation of resistance to proliferative
      kidney disease in rainbow trout Oncorhynchus mykiss (Walbaum) following
      experimental re-exposure.
AB  - Rainbow trout Oncorhynchus mykiss surviving proliferative kidney disease (PKD)
      are reported not to develop the disease upon re-exposure. However, the mechanisms
      involved in the immune response to re-exposure are unknown. We examined disease
      susceptibility and the immune response of naive 1+ rainbow trout when first
      exposed to Tetracapsuloides bryosalmonae in comparison with that of 1+ rainbow
      trout re-exposed to T. bryosalmonae. PKD pathogenesis, parasite burden and
      transcriptional signatures of the host immune response were assessed at 10, 25
      and 40 d.p.e (days post-exposure). In addition, we evaluated the presence of IgM+
      B cells in the blood and the posterior kidney. The exposure of 1+ rainbow trout
      to T. bryosalmonae for the first time resulted in 100% infection prevalence, high
      parasite burdens and severe clinical PKD, while re-exposed fish were either able
      to avoid reinfection completely or mount an earlier and more efficient adaptive
      type immune response. This response was characterized by a greater amount of IgM+
      B cells in the blood and elevated mRNA levels of secretory IgM in the posterior
      kidney which minimized pathogen burden and kidney inflammation. Our findings
      suggest that rainbow trout is able to develop immune protection against T.
      bryosalmonae.

PMID- 28429823
TI  - Changes in the gut microbiome of the Chinese mitten crab (Eriocheir sinensis) in
      response to White spot syndrome virus (WSSV) infection.
AB  - Intestinal microorganisms play important roles in maintaining host health, but
      their functions in aquatic animal hosts have yet to be fully elucidated. The
      Chinese mitten crab, Eriocheir sinensis, is one such example. We attempted to
      identify the shift of gut microbiota that occurred in response to infection of
      white spot syndrome virus (WSSV), an emerging viral pathogen in the crab
      aquaculture industry. The microbiota may exert some control over aspects of the
      viral pathogenesis. We investigated the changes in composition and structure of
      the crab gut microbiome during various WSSV infection stages of 6 h post
      infection (hpi) and 48 hpi, using a 16S rRNA approach on the MiSeq Illumina
      sequencing platform. Four phyla (Firmicutes, Proteobacteria, Tenericutes and
      Bacteroidetes) were most dominant in the gut of E. sinensis regardless of the
      WSSV infection stages. However, further analysis revealed that over 12 bacterial
      phyla, 44 orders and 68 families were significantly different in abundance at
      various states of WSSV infection. Several intriguing aspects of E. sinensis gut
      bacteria that had not been previously reported were also uncovered, such as class
      Mollicutes was dominant here, but absent in crabs from Yangtze River estuary and
      Chongming Islands. Overall, this study provided the first evidence that changes
      in gut microbiome were closely associated with the severity of WSSV infection and
      that indicator taxa could be used to evaluate the crab health status.

PMID- 28429824
TI  - Application of an embryonated chicken egg model to assess the vector competence
      of Australian Culicoides midges for bluetongue viruses.
AB  - Culicoides biting midges (Diptera: Ceratopogonidae) are vectors of a number of
      globally important arboviruses that affect livestock, including bluetongue virus
      (BTV), African horse sickness virus and the recently emerged Schmallenberg virus.
      In this study, a model using embryonated chicken eggs (ECEs) was utilized to
      undertake vector competence studies of Australian Culicoides spp. for 13
      laboratory-adapted or wild-type virus strains of BTV. A total of 7393 Culicoides
      brevitarsis were reared from bovine dung, and 3364 Culicoides were induced to
      feed from ECEs infected with different strains of BTV. Of those, 911 (27%)
      survived the putative extrinsic incubation period of 9-12 days. In some trials,
      virus was also transmitted onward to uninfected ECEs, completing the transmission
      cycle. This model does not rely on the use of colonized midges and has the
      capacity to assess the vector competence of field-collected insects with strains
      of virus that have not previously been passaged in laboratory culture systems.
      There is also potential for this model to be used in investigations of the
      competence of Culicoides spp. for other arboviruses.

PMID- 28429825
TI  - Validation of the MDS research criteria for prodromal Parkinson's disease:
      Longitudinal assessment in a REM sleep behavior disorder (RBD) cohort.
AB  - BACKGROUND: Recently, the International Parkinson and Movement Disorder Society
      introduced the prodromal criteria for PD. Objectives Our study aimed to examine
      diagnostic accuracy of the criteria as well as the independence of prodromal
      markers to predict conversion to PD or dementia with Lewy bodies. METHODS: This
      prospective cohort study was performed on 121 individuals with rapid eye movement
      sleep behavior disorder who were followed annually for 1 to 12 years. Using data
      from a comprehensive panel of prodromal markers, likelihood ratio and post-test
      probability of the criteria were calculated at baseline and during each follow-up
      visit. RESULTS: Forty-eight (39.7%) individuals with rapid eye movement sleep
      behavior disorder converted to PD/dementia with Lewy bodies. The prodromal
      criteria had 81.3% sensitivity and 67.9% specificity for conversion to
      PD/dementia with Lewy bodies at 4-year follow-up. One year before conversion,
      sensitivity was 100%. The criteria predicted dementia with Lewy bodies with even
      higher accuracy than PD without dementia at onset. Those who met the threshold of
      prodromal criteria at baseline had significantly more rapid conversion into a
      neurodegenerative state (4.8 vs. 9.1 years; P < 0.001). Pair-wise combinations of
      different prodromal markers showed that markers were independent of one another.
      CONCLUSION: The prodromal criteria are a promising tool for predicting incidence
      of PD/dementia with Lewy bodies and conversion time in a rapid eye movement sleep
      behavior disorder cohort, with high sensitivity and high specificity with long
      follow-up. Prodromal markers influence the overall likelihood ratio
      independently, allowing them to be reliably multiplied. Defining additional
      markers with high likelihood ratio, further studies with longitudinal assessment
      and testing thresholds in different target populations will improve the criteria.
      (c) 2017 International Parkinson and Movement Disorder Society.

PMID- 28429826
TI  - Effect of alpha-lipoic acid on endometrial implants in an experimental rat model.
AB  - To investigate the antioxidant and anti-inflammatory effects of alpha-lipoic acid
      (ALA) in the treatment of endometriosis in an experimental rat model by
      evaluating biochemical and histopathologic parameters. Experimental endometriosis
      was induced by the peritoneal implantation of autologous endometrial tissue. The
      rats were randomly divided into two groups with eight rats each. Group I was
      intraperitoneally administered ALA 100 mg/kg/day for 14 days. Group II was
      intraperitoneally administered saline solution at the same dosage and over the
      same period. Endometrial implant volume was measured in both groups both pre- and
      post-treatment. Tumor necrosis factor alpha (TNF-alpha) was measured in
      peritoneal fluid. Total antioxidant status (TAS), total oxidant status (TOS), and
      oxidative stress index (OSI) were assessed in serum. The implants were
      histopathologically evaluated. In the ALA group, the serum TOS and OSI levels,
      the endometrial implant volumes, the TNF-alpha levels in serum and peritoneal
      fluid, and the histopathologic scores were significantly lower compared to the
      control group (P < 0.05). Alpha-lipoic acid may have a therapeutic potential in
      the treatment of endometriosis due to its antioxidant and anti-inflammatory
      effects.

PMID- 28429827
TI  - A descriptive and broadly applicable model of therapeutic and stray absorbed dose
      from 6 to 25 MV photon beams.
AB  - PURPOSE: To develop a simple model of therapeutic and stray absorbed dose for a
      variety of treatment machines and techniques without relying on proprietary
      machine-specific parameters. METHODS: Dosimetry measurements conducted in this
      study and from the literature were used to develop an analytical model of
      absorbed dose from a variety of treatment machines and techniques in the 6 to 25
      MV interval. A modified one-dimensional gamma-index analysis was performed to
      evaluate dosimetric accuracy of the model on an independent dataset consisting of
      measured dose profiles from seven treatment units spanning four manufacturers.
      RESULTS: The average difference between the calculated and measured absorbed dose
      values was 9.9% for those datasets on which the model was trained. Additionally,
      these results indicate that the model can provide accurate calculations of both
      therapeutic and stray radiation dose from a wide variety of radiotherapy units
      and techniques. CONCLUSIONS: We have developed a simple analytical model of
      absorbed dose from external beam radiotherapy treatments in the 6 to 25 MV beam
      energy range. The model has been tested on measured data from multiple treatment
      machines and techniques, and is broadly applicable to contemporary external beam
      radiation therapy.

PMID- 28429828
TI  - Genomic clustering of adaptive loci during parallel evolution of an Australian
      wildflower.
AB  - The build-up of the phenotypic differences that distinguish species has long
      intrigued biologists. These differences are often inherited as stable
      polymorphisms that allow the cosegregation of adaptive variation within species,
      and facilitate the differentiation of complex phenotypes between species. It has
      been suggested that the clustering of adaptive loci could facilitate this
      process, but evidence is still scarce. Here, we used QTL analysis to study the
      genetic basis of phenotypic differentiation between coastal populations of the
      Australian wildflower Senecio lautus. We found that a genomic region consistently
      governs variation in several of the traits that distinguish these contrasting
      forms. Additionally, some of the taxon-specific traits controlled by this QTL
      cluster have evolved repeatedly during the adaptation to the same habitats,
      suggesting that it could mediate divergence between locally adapted forms. This
      cluster contains footprints of divergent natural selection across the range of S.
      lautus, which suggests that it could have been instrumental for the rapid
      diversification of this species.

PMID- 28429829
TI  - Molecular adaptation in the world's deepest-living animal: Insights from
      transcriptome sequencing of the hadal amphipod Hirondellea gigas.
AB  - The Challenger Deep in the Mariana Trench is the deepest point in the oceans of
      our planet. Understanding how animals adapt to this harsh environment
      characterized by high hydrostatic pressure, food limitation, dark and cold is of
      great scientific interest. Of the animals dwelling in the Challenger Deep,
      amphipods have been captured using baited traps. In this study, we sequenced the
      transcriptome of the amphipod Hirondellea gigas collected at a depth of 10,929 m
      from the East Pond of the Challenger Deep. Assembly of these sequences resulted
      in 133,041 contigs and 22,046 translated proteins. Functional annotation of these
      contigs was made using the go and kegg databases. Comparison of these translated
      proteins with those of four shallow-water amphipods revealed 10,731 gene
      families, of which 5659 were single-copy orthologs. Base substitution analysis on
      these single-copy orthologs showed that 62 genes are positively selected in H.
      gigas, including genes related to beta-alanine biosynthesis, energy metabolism
      and genetic information processing. For multiple-copy orthologous genes, gene
      family expansion analysis revealed that cold-inducible proteins (i.e.,
      transcription factors II A and transcription elongation factor 1) as well as zinc
      finger domains are expanded in H. gigas. Overall, our results indicate that
      genetic adaptation to the hadal environment by H. gigas may be mediated by both
      gene family expansion and amino acid substitutions of specific proteins.

PMID- 28429830
TI  - Establishment and evaluation of a novel biomarker-based nomogram for malignant
      phaeochromocytomas and paragangliomas.
AB  - OBJECTIVE: No single histological or molecular marker is diagnostic for malignant
      phaeochromocytomas and paragangliomas (PPGLs). This study aimed to establish and
      evaluate a prognostic nomogram to improve the prediction of metastatic
      probability in individual PPGL patients. METHODS: Three hundred and 47
      consecutive PPGL patients from January 2002 through December 2014 were randomly
      divided into a training set (n=208) and a validation set (n=139). A multivariate
      logistic regression analysis of selected prognostic features was performed, and a
      nomogram to predict metastasis was constructed. Discrimination and calibration
      were employed to evaluate the performance of the nomogram. Clinical usefulness
      was calculated using decision curve analysis. RESULTS: The overall metastatic
      rate was 10.6%. Primary tumour size, primary tumour location, vascular invasion,
      ERBB-2 overexpression, SDHB mutation and catecholamine type were associated with
      malignancy in the logistic analysis and were included in the nomogram. The
      nomogram showed an area under the receiver operating characteristic curve (AUC)
      of 0.872 (95% confidence interval [CI], 0.819-0.914) in the training set. The
      validation set showed good discrimination, with an AUC of 0.870 (95% CI, 0.803
      0.921). The nomogram was well calibrated, with no significant difference between
      the predicted and the observed probabilities (Hosmer-Lemeshow test: P=.510 for
      the training set; .314 for the validation set). Decision curve analysis revealed
      that molecular markers (ERBB-2 overexpression and SDHB mutation) could increase
      the clinical benefit of the nomogram. CONCLUSION: Our results support the use of
      the present biomarker-based nomogram, which has good discriminative ability, to
      predict the metastatic probability of PPGLs.

PMID- 28429831
TI  - One-Step Fabrication of Monolithic Electrodes Comprising Co9 S8 Particles
      Supported on Cobalt Foam for Efficient and Durable Oxygen Evolution Reaction.
AB  - A very easy and cost-effective approach to the fabrication of monolithic Co9 S8
      water oxidation electrodes (Co@Co9 S8 ), fabricated by one-step hydrothermal
      treatment of commercially available cobalt foam in the presence of thiourea, is
      reported. The morphology, crystal structure, microstructure, and composition of
      as-fabricated Co@Co9 S8 electrodes were examined by using scanning electron
      microscopy (SEM), powder X-ray diffractometry (XRD), transmission electron
      microscope (TEM), and X-ray photoelectron spectroscopy (XPS), and their
      electrochemical properties were investigated by cyclic voltammetry (CV),
      chronopotentiometry (CP), chronoamperometry (CA), and electrochemical impedance
      spectroscopy (EIS). When used to catalyze the oxygen evolution reaction (OER) in
      alkaline solution, the Co@Co9 S8 electrode with an optimal Co9 S8 loading
      exhibits outstanding catalytic activity, requiring a low overpotential of 350 mV
      to deliver an anodic current density of 10 mA cm-2 and showing fast kinetics for
      OER with a small Tafel slope (55 mV dec-1 ) and charge-transfer resistance (0.44
      Omega cm-2 ), which outperforms many sulfide-based OER catalysts and some state
      of-the-art noble metal catalysts recently reported in the literature.
      Importantly, the electrodes show excellent long-term stability, and are capable
      of operating at both a low current density and a high current density relevant to
      industrial water electrolysis up to 100 hours.

PMID- 28429834
TI  - Surgical procedures for benign prostatic hyperplasia: A nationwide survey in
      Japan, 2014 update.

PMID- 28429833
TI  - The microbially mediated soil organic carbon loss under degenerative succession
      in an alpine meadow.
AB  - Land-cover change has long been recognized as having marked effect on the amount
      of soil organic carbon (SOC). However, the microbially mediated processes and
      mechanisms on SOC are still unclear. In this study, the soil samples in a
      degenerative succession from alpine meadow to alpine steppe meadow in the Qinghai
      Tibetan Plateau were analysed using high-throughput technologies, including
      Illumina sequencing and geochip functional gene arrays. The soil microbial
      community structure and diversity were significantly (p < .05) different between
      alpine meadow and alpine steppe meadow; the microbial alpha-diversity in alpine
      steppe meadow was significantly (p < .01) higher than in alpine meadow. Molecular
      ecological network analysis indicated that the microbial community structure in
      alpine steppe meadow was more complex and tighter than in the alpine meadow. The
      relative abundance of soil microbial labile carbon degradation genes (e.g.,
      pectin and hemicellulose) was significantly higher in alpine steppe meadow than
      in alpine meadow, but the relative abundance of soil recalcitrant carbon
      degradation genes (e.g., chitin and lignin) showed the opposite tendency. The
      Biolog Ecoplate experiment showed that microbially mediated soil carbon
      utilization was more active in alpine steppe meadow than in alpine meadow.
      Consequently, more soil labile carbon might be decomposed in alpine steppe meadow
      than in alpine meadow. Therefore, the degenerative succession of alpine meadow
      because of climate change or anthropogenic activities would most likely decrease
      SOC and nutrients medicated by changing soil microbial community structure and
      their functional potentials for carbon decomposition.

PMID- 28429832
TI  - A genetic risk score that includes common type 2 diabetes risk variants is
      associated with gestational diabetes.
AB  - OBJECTIVE: Gestational diabetes (GDM) is characterized by maternal glucose
      intolerance that manifests during pregnancy. Because GDM resembles type 2
      diabetes (T2DM), shared genetic predisposition is likely but has not been
      established. We tested the hypothesis that a genetic risk score (GRS) that
      included variants known to be associated with T2DM is associated with GDM. STUDY
      DESIGN: We conducted a case-control study using the Vanderbilt Medical Center
      biobank (BioVU) and calculated a simple-count GRS using 34 variants previously
      associated with T2DM or fasting glucose in the general population, or with GDM or
      glucose intolerance in pregnancy. We assessed the association of the GRS with GDM
      adjusting for maternal age, parity, and body mass index (BMI) and calculated the
      area under the curve for the receiver-operating characteristic curve (c
      statistic). STUDY POPULATION: Among Caucasian women, we identified 458 cases of
      GDM and 1538 pregnant controls with normal glucose tolerance. RESULTS: Cases of
      GDM had a higher number of risk alleles compared to controls (38.9+/-4.0 vs
      37.4+/-4.0 risk alleles, P=1.6*10-11 ). The GRS was significantly associated with
      GDM; the adjusted odds ratio associated with each additional risk allele was 1.10
      (95% CI: 1.07-1.13, P=6*10-11 ). Clinical variables predicted the risk of GDM (c
      statistic 0.67, 95% CI: 0.64-0.70), and adding the GRS modestly improved
      prediction (0.70, 95% CI: 0.67-0.73). CONCLUSIONS: Among Caucasian women, a GRS
      that included common T2DM genetic risk variants was associated with increased
      risk of GDM but showed limited utility in the identification of GDM cases.

PMID- 28429835
TI  - Levodopa prevents the reinstatement of cocaine self-administration in rats via
      potentiation of dopamine release in the medial prefrontal cortex.
AB  - Dopamine agonists have been proposed as therapeutic tools for cocaine addiction.
      We have recently demonstrated that indirect dopamine agonists, including levodopa
      (L-DOPA), markedly increase cocaine-induced dopamine release in the medial
      prefrontal cortex (mPFC) of rats leading to the suppression of cocaine-seeking
      behavior. This study was aimed to understand the behavioral and neurochemical
      effects of L-DOPA on cocaine-taking and cocaine-seeking in rats. After reaching a
      stable pattern of intravenous cocaine self-administration under a continuous
      fixed ratio (FR-1) schedule of reinforcement, male rats were treated with L-DOPA
      at different steps of the self-administration protocol. We found that L-DOPA
      reduced cocaine self-administration under FR-1 schedule of reinforcement and
      decreased the breaking points and the amount of cocaine self-administered under
      the progressive ratio schedule of reinforcement. Levodopa also decreased cocaine
      seeking behavior both in a saline substitution test and in the cue priming
      induced reinstatement test, without affecting general motor activity.
      Importantly, L-DOPA greatly potentiated cocaine-induced dopamine release in the
      mPFC of self-administering rats while reducing their cocaine intake. In the same
      brain area, L-DOPA also increased dopamine levels during cue priming-induced
      reinstatement of cocaine-seeking behavior. The potentiating effect was also
      evident in the mPFC but not nucleus accumbens core of drug-naive rats passively
      administered with cocaine. Altogether, these findings demonstrate that L-DOPA
      efficaciously reduces the reinforcing and motivational effects of cocaine likely
      potentiating dopamine transmission in the mPFC. Its ability to prevent cue
      priming-induced reinstatement of cocaine-seeking suggests that it might be
      effective in reducing the risk to relapse to cocaine in abstinent patients.

PMID- 28429836
TI  - Increased levels of soluble HLA-G molecules in Tunisian patients with chronic
      hepatitis B infection.
AB  - Hepatitis B virus (HBV) infection is a global health problem. The mechanisms of
      immune tolerance in HBV infection are still unclear. The host immune response
      plays a critical role in determining the outcome of HBV infection. Human
      leucocyte antigen-G (HLA-G) is involved in immunotolerogenic process and
      infectious diseases. This study aimed to explore the implication of soluble HLA-G
      (sHLA-G) and its isoforms in HBV infection. Total sHLA-G (including shedding HLA
      G1 and HLA-G5) was analysed by ELISA in 95 chronic HBV patients, 83 spontaneously
      resolvers and 100 healthy controls (HC). To explore the presence of sHLA-G
      dimers, we performed an immunoprecipitation and a Western blot analysis on
      positive samples for sHLA-G in ELISA. The serum levels of sHLA-G were
      significantly increased in patients with chronic HBV patients compared to
      spontaneously resolvers and HC (P<.0001). Interestingly, we found an increased
      level of sHLA-G1 in chronic HBV patients than in spontaneously resolvers and HC
      (P<.001). In addition, the expression of HLA-G5 seems to be higher in the sera of
      chronic HBV patients than spontaneously resolvers (P=.026). The analysis of HLA-G
      dimers showed the presence of homodimers in 93% of chronic HBV patients, 67% in
      spontaneously resolvers and 60% in HC. These results provide evidence that sHLA-G
      may have a crucial role in the outcome of HBV infection and could be proposed as
      a biomarker for infection outcome. Based on its tolerogenic function, HLA-G might
      be considered as a new promising immunotherapeutic approach to treat the chronic
      infection with HBV.

PMID- 28429837
TI  - Fluorescence-based sensor for selective and sensitive detection of amoxicillin
      (Amox) in aqueous medium: Application to pharmaceutical and biomedical analysis.
AB  - We here for the first time demonstrate an analytical approach for the highly
      selective and sensitive detection of amoxicillin (Amox) in aqueous medium based
      on the fluorescence quenching of quantum dots (QDs). The change in fluorescence
      intensity of mercaptopropionic acid-capped cadmium sulphide (MPA-CdS) QDs is
      attributed to the increasing concentration of Amox. The results show that the
      fluorescence quenching of QDs by Amox takes place through both static and dynamic
      types of quenching mechanism. The fluorescence quenching of QDs with increase in
      concentration of Amox shows the linear range between 5 MUg ml-1 and 30 MUg ml-1
      and the limit of detection (LOD) is 5.19 MUg ml-1 . There is no interference of
      excipients, which are commonly present in pharmaceutical formulation and urine
      samples. For the practical application approach, the developed method has been
      successfully applied for the determination of Amox in pharmaceutical formulations
      and urine samples with acceptable results.

PMID- 28429838
TI  - Pyrophosphate as substrate for alkaline phosphatase activity: A convenient flow
      injection chemiluminescence assay.
AB  - A sensitive and convenient flow-injection chemiluminescence (FI-CL) turn-on assay
      for alkaline phosphatase (ALP) activity without any label and synthesis is
      developed. Cu2+ can catalyze the luminol-H2 O2 CL reaction. Pyrophosphate (PPi)
      can chelate Cu2+ and therefore the Cu2+ -mediated luminol-H2 O2 CL reaction is
      inhibited. The addition of ALP can catalyze the hydrolysis of PPi into phosphate
      ions, Cu2+ is released and the chemiluminescence recovers. A detection limit of 1
      mU/mL ALP is obtained.

PMID- 28429839
TI  - Pursuing the second ipsilateral gland during minimally invasive video-assisted
      parathyroidectomy.
AB  - BACKGROUND: In patients with primary hyperparathyroidism (PHPT) and preoperative
      imaging suggesting a solitary parathyroid adenoma (SPA), focused
      parathyroidectomy is most often curative. Even so, large studies show up to 3% of
      patients experience persistent or recurrent PHPT. Unilateral neck exploration
      (UNE) aiming to identify the SPA and the other ipsilateral parathyroid may reduce
      this failure rate. We hypothesized that: (i) minimally invasive video-assisted
      (MIVA) approach would facilitate UNE and (ii) this would be a clinically relevant
      strategy. METHODS: Prospective case series of a consecutive cohort of PHPT
      patients (with preoperative diagnosis of SPA), who underwent MIVA-UNE. A 15 mm
      collar incision and endoscopic magnification were utilized to both excise the SPA
      and seek the ipsilateral parathyroid gland. RESULTS: From 2009 to 2014, 132
      patients were offered MIVA-UNE (age: 63.0 (interquartile range: 11.2); females:
      94 (71.2%); symptomatic: 89 (67.4%); mean serum corrected calcium: 2.7 (standard
      deviation: 0.9) mmol/L; mean serum parathyroid hormone: 16.8 (standard deviation:
      11.8) pmol/L). Conversion from MIVA-UNE to open UNE was required in 14 (10.6%)
      patients (excluded from subsequent analysis). MIVA-UNE was concluded in 118
      patients. The second ipsilateral parathyroid was identified in 62 (52.5%)
      patients and in 13 (11.0%) it appeared enlarged and was excised. Histopathology
      confirmed five (4.2%) of these glands to be hyperplastic. CONCLUSION: MIVA-UNE
      allows identification of the second ipsilateral parathyroid in about half the
      patients. This approach helped to diagnose and treat unexpected multigland
      disease in almost 5% of patients.

PMID- 28429840
TI  - Non-response to fluconazole maintenance treatment (ReCiDiF regimen) for recurrent
      vulvovaginal candidosis is not related to impaired glucose metabolism.
AB  - Is non-response to maintenance treatment for recurrent vulvovaginal candidosis
      (RCVV) related to the impaired glucose metabolism? In the ReCiDiF trial, women
      with RCVV were given a degressive regimen with fluconazole according to their
      clinical, microscopic and mycologic response. Data obtained from optimal,
      suboptimal and non-reponding patients were used for secondary analysis of medical
      history, physical status and family history for potential glucose impairment.
      Results were presented in means and percentages. Pearson chi-square, Fisher
      exact, Mann-Whitney U, Kruskal-Wallis and Spearman's correlation coefficient was
      calculated. P<.05 were interpreted as statistically significant. Sociodemographic
      characteristics and family and personal history of diabetes were not different
      between optimal, suboptimal and non-responders. The average HbA1c concentration
      was 5.1+/-0.3% in optimal, 5.0+/-0.4% in sub-optimal, and 5.1+/-0.3% in non
      responding patients (P=1.0). There are no statistical differences between
      optimal, sub-optimal and non-respondents to treatment in all deciles of HbA1c
      among patients with recurrent candidosis (P=1.0). There was no difference among
      groups in fasting glucose concentration, nor after 30 min, 60 min or 120 min
      during the oral glucose tolerance test (OGTT) (P=.6). Area under the OGTT curve
      did not differ within groups (P=.8), nor was the deviation from the normal cut
      off value any different (P=.8). Glucose concentration in vaginal rinsing fluid
      showed no correlation with responsiveness to treatment (P=.7). Glucose
      metabolism, BMI, personal or family history of diabetes are not related to non
      response to maintenance treatment with fluconazole for patients with RVVC.

PMID- 28429841
TI  - The development, evidence, and current use of ATX-101 for the treatment of
      submental fat.
AB  - ATX-101 (deoxycholic acid) is the first pharmaceutical therapy approved by the
      FDA for the reduction in submental fat. Deoxycholic acid is an endogenous
      secondary bile acid that normally solubilizes dietary fat, contributing to its
      breakdown and absorption within the gut. This article reviews the identification
      of deoxycholic acid as a lipolytic agent, and the mechanism of action,
      pharmacokinetics, and pharmacodynamics of ATX-101. In addition to phase I/II
      trials, four Phase III clinical trials have evaluated safety and efficacy of ATX
      101. These studies helped establish the appropriate dosage, administration
      techniques, warnings, and side effects of ATX-101. ATX-101 is effective in
      treating submental fat. Adverse events, although common, are mild and transient.

PMID- 28429842
TI  - Linking macroecology and community ecology: refining predictions of species
      distributions using biotic interaction networks.
AB  - Macroecological models for predicting species distributions usually only include
      abiotic environmental conditions as explanatory variables, despite knowledge from
      community ecology that all species are linked to other species through biotic
      interactions. This disconnect is largely due to the different spatial scales
      considered by the two sub-disciplines: macroecologists study patterns at large
      extents and coarse resolutions, while community ecologists focus on small extents
      and fine resolutions. A general framework for including biotic interactions in
      macroecological models would help bridge this divide, as it would allow for
      rigorous testing of the role that biotic interactions play in determining species
      ranges. Here, we present an approach that combines species distribution models
      with Bayesian networks, which enables the direct and indirect effects of biotic
      interactions to be modelled as propagating conditional dependencies among
      species' presences. We show that including biotic interactions in distribution
      models for species from a California grassland community results in better range
      predictions across the western USA. This new approach will be important for
      improving estimates of species distributions and their dynamics under
      environmental change.

PMID- 28429843
TI  - Pooled analysis of three randomized, double-blind, placebo controlled trials with
      rimonabant for smoking cessation.
AB  - Despite the withdrawal of CB1 antagonists, such as rimonabant, from the market
      and from active clinical development because of concerns about their side effect
      profiles, research suggests that the endocannabinoid system may play an important
      role in modulating nicotine's effects. We report the combined results, using a
      pooled analysis, of three previously unpublished trials assessing rimonabant as a
      smoking cessation pharmacotherapy conducted between 2002 and 2004. Smokers (n =
      2097) motivated to quit were enrolled in three randomized, double-blind, placebo
      controlled trials, STRATUS EU, US, and META, which consisted of a 10-week
      treatment period with either rimonabant 20 mg (n = 789), 5 mg (n = 518; used in
      only two of the three studies), or placebo (n = 790), in conjunction with brief
      counseling. The impact of drug on prolonged abstinence and adverse events was
      examined at 8 weeks (end-of-treatment) and at 48 weeks (available for STRATUS EU
      and US) after the targeted quit date. Rimonabant 20 mg resulted in significantly
      higher abstinence at end-of-treatment and at 48 weeks post-targeted quit date
      compared with placebo, while rimonabant 5 mg and placebo did not differ. Serious
      AEs did not differ by drug group. The 20 mg rimonabant dose, compared with
      placebo, produced increased nausea, diarrhea, anxiety symptoms, hyporexia, and
      vomiting, and decreased headache, constipation, and cough. These results support
      rimonabant 20 mg as a modestly effective aid for smoking cessation. Although work
      on CB1 antagonists such as rimonabant has mostly been stopped because of
      unacceptable adverse events, these results may inform and spur the development of
      other endocannabinoids for smoking cessation.

PMID- 28429844
TI  - A comparison of clinical characteristics of older adults treated with
      antidepressants in general and psychiatric hospitals in Asia.
AB  - AIM: This study compared the demographics, clinical characteristics, and
      antidepressant prescription patterns between Asian patients aged 50 years and
      older attending psychiatric hospitals and those attending general hospitals.
      METHODS: In total, 955 patients (604 in general hospitals, 351 in psychiatric
      hospitals) aged 50 years or older treated with antidepressants in 10 Asian
      countries and territories were examined. Patients' demographics, clinical
      features, and prescriptions of psychotropic drugs were recorded using a
      standardized protocol and data collection procedure. RESULTS: Binary logistic
      regression revealed that high income and diagnosis of schizophrenia were
      independently associated with psychiatric hospital treatment, whereas outpatient
      care, diagnosis of anxiety disorders, and multiple major medical conditions were
      independently associated with general hospital treatment. In addition,
      tetracyclic and noradrenergic and specific serotonergic antidepressants were more
      likely to be prescribed in general hospitals. CONCLUSION: Older adults treated
      with antidepressants showed different demographic and clinical features between
      general hospitals and psychiatric hospitals in Asia.

PMID- 28429845
TI  - Following nature's roadmap: folding factors from plasma cells led to improvements
      in antibody secretion in S. cerevisiae.
AB  - Therapeutic protein production in yeast is a reality in industry with an untapped
      potential to expand to more complex proteins, such as full-length antibodies.
      Despite numerous engineering approaches, cellular limitations are preventing the
      use of Saccharomyces cerevisiae as the titers of recombinant antibodies are
      currently not competitive. Instead of a host specific approach, the possibility
      of adopting the features from native producers of antibodies, plasma cells, to
      improve antibody production in yeast. A subset of mammalian folding factors
      upregulated in plasma cells for expression in yeast and screened for beneficial
      effects on antibody secretion using a high-throughput ELISA platform was
      selected. Co-expression of the mammalian chaperone BiP, the co-chaperone GRP170,
      or the peptidyl-prolyl isomerase FKBP2, with the antibody improved specific
      product yields up to two-fold. By comparing strains expressing FKBP2 or the yeast
      PPIase Cpr5p, the authors demonstrate that speeding up peptidyl-prolyl
      isomerization by upregulation of catalyzing enzymes is a key factor to improve
      antibody titers in yeast. The findings show that following the route of plasma
      cells can improve product titers and contribute to developing an alternative
      yeast-based antibody factory.

PMID- 28429846
TI  - Protected engagement time on older adult mental health wards: A thematic analysis
      of the views of patients, carers, and staff.
AB  - During protected engagement time (PET), ward routines are adjusted so that staff
      can spend time together with patients without interruption. The aim of PET is to
      increase staff and patient interaction on wards, and ultimately patient well
      being. Although PET has been implemented on inpatient wards within the UK,
      including older adult wards, there is no systematic evidence as to how PET is
      carried out or how it is experienced by staff, patients, and families.
      Semistructured interviews were conducted with 28 participants (8 patients, 10
      family members, and 10 ward staff) from three different wards with PET, and
      transcriptions were analysed using thematic analysis. Three themes were
      identified: (i) the patient is at the heart of care; (ii) PET depends on staff;
      and (iii) tensions in how PET operates. There was support in our sample for the
      principles of PET and its potential for a positive impact on patient well-being.
      However, the implementation of PET was identified as challenging, highlighting an
      existing tension between an individual's needs and the wider needs of patients on
      the ward as a whole. The impact of PET was generally described as being dependent
      on how PET was organized and the level of staff commitment to PET. Participants
      emphasized that if PET is to be successful, then it should be a fluid process
      that fits in with the local context.

PMID- 28429847
TI  - Outcome of individuals "not at risk of psychosis" and prognostic accuracy of the
      Basel Screening Instrument for Psychosis (BSIP).
AB  - BACKGROUND: We aimed to determine the prognostic accuracy of the Basel Screening
      Instrument for Psychosis (BSIP) in terms of specificity, sensitivity, positive
      and negative predictive value by following up individuals that were initially not
      considered to be at increased risk of psychosis based on the BSIP. Moreover,
      clinical characteristics of these individuals were examined given the relative
      lack of such information in the literature. METHODS: As part of the
      "Fruherkennung von Psychosen" (FePsy) study, 87 individuals were screened with
      the BSIP. Of these, 64 were classified at baseline as being in an at-risk mental
      state (ARMS+) for psychosis using the BSIP and followed up at regular time
      intervals for at least 2 years to determine a putative transition to psychosis.
      Twenty-three individuals were classified at baseline as not being in an at-risk
      mental state (ARMS-) using the BSIP and re-assessed after 4 years. Sensitivity,
      specificity, positive and negative predictive value of the BSIP were computed.
      Clinical characteristics of the ARMS- group were analysed descriptively. RESULTS:
      During the follow-up period, none of the ARMS- individuals, but 21 of ARMS+ had
      developed psychosis. Sensitivity of the BSIP was 1.0, specificity was 0.35. The
      majority of ARMS- individuals showed depressive disorders or anxiety disorders
      and varying levels of functioning. CONCLUSIONS: The BSIP has good prognostic
      accuracy for detecting the prodromal phase of psychosis with an excellent
      sensitivity and a specificity similar to other risk instruments and the advantage
      of a relatively short duration. Depressive and anxiety symptoms commonly develop
      in ARMS- individuals.

PMID- 28429849
TI  - Public Support in the U.S. for Human-Animal Chimera Research: Results of a
      Representative Cross-Sectional Survey of 1,058 Adults.

PMID- 28429848
TI  - Stuck in fragments: Population genetics of the Endangered collared brown lemur
      Eulemur collaris in the Malagasy littoral forest.
AB  - OBJECTIVES: The Endangered collared brown lemur (Eulemur collaris) is the largest
      primate living in the littoral forest of southeastern Madagascar, a top priority
      habitat for biodiversity conservation on the island. Because this lemur is a key
      seed-disperser, an evaluation of the structure and connectivity of the
      populations surviving in the forest fragments is urgently needed to guide
      conservation plans. MATERIALS AND METHODS: Genetic variability at autosomal
      microsatellites and mitochondrial DNA was investigated in a total of 49 collared
      brown lemurs sampled by non-invasive methods in three littoral forest fragments
      and in the nearby lowland humid forest. RESULTS: The overall genetic diversity of
      E. collaris in the southeastern coastal region of Madagascar was lower than in
      other populations, as well as in other lemur species. The population appears
      highly structured, with less variable and more inbred groups inhabiting the
      littoral forest fragments compared to the inland area. Major barriers to gene
      flow were identified isolating littoral forest fragments from each other and from
      the inland lowland humid forest. DISCUSSION: Medium to long-term drift and scarce
      gene flow is the scenario that best explains the current genetic distribution.
      Habitat discontinuities such as rivers and grassland between forest fragments
      played a major role in structuring the population. A common history of size
      contraction is pointed out by several genetic estimators, indicating a possible
      ecological crisis triggered around 1,300 years ago. The adoption of strategies
      aimed at facilitating gene flow and population growth appears crucial to delay
      further loss of genetic diversity.

PMID- 28429851
TI  - Impacts of taxonomic inertia for the conservation of African ungulate diversity:
      an overview.
AB  - We review the state of African ungulate taxonomy over the last 120 years, with an
      emphasis on the introduction of the polytypic species concept and the
      discipline's general neglect since the middle of the 20th century. We single out
      negative consequences of 'orthodox' taxonomy, highlighting numerous cases of
      neglect of threatened lineages, unsound translocations that led to lineage
      introgression, and cases of maladaptation to local conditions including parasitic
      infections. Additionally, several captive breeding programmes have been hampered
      by chromosome rearrangements caused by involuntary lineage mixing. We advocate
      that specimen-based taxonomy should regain its keystone role in mammal research
      and conservation biology, with its scientific values augmented with genomic
      evidence. While integration with molecular biology, ecology and behaviour is
      needed for a full understanding of ungulate alpha diversity, we stress that
      morphological diversity has been neglected despite its tremendous practical
      importance for some groups of 'utilizers' such as trophy hunters, wildlife
      tourists and conservationists. We conclude that there is no evidence that
      purported 'taxonomic inflation' has adverse effects on ungulate conservation:
      rather, it is taxonomic inertia that has such adverse effects. We stress that
      sound science, founded on robust taxonomy, should underpin effective sustainable
      management (hunting, ranching, captive breeding and reintroduction programmes) of
      this unique African natural resource.

PMID- 28429850
TI  - Association of obstructive sleep apnea with arterial stiffness and nondipping
      blood pressure in patients with hypertension.
AB  - Whether sex influences the association of obstructive sleep apnea (OSA) with
      markers of cardiovascular risk in patients with hypertension is unknown. In this
      study, 95 hypertensive participants underwent carotid-femoral pulse wave
      velocity, 24-hour ambulatory blood pressure monitoring, echocardiogram, and
      polysomnography after a 30-day standardized treatment with hydrochlorothiazide
      plus enalapril or losartan. OSA was present in 52 patients. Compared with non-OSA
      patients, pulse wave velocity values were higher in the OSA group (men: 11.1+/
      2.2 vs 12.7+/-2.4 m/s, P=.04; women: 11.8+/-2.4 vs 13.2+/-2.2 m/s, P=.03). The
      proportion of diastolic dysfunction was significant in men and women with OSA.
      Compared with non-OSA patients, nondipping systolic blood pressure in OSA was
      higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was
      independently associated with pulse wave velocity (beta=1.050; P=.025) and
      nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval,
      1.08-8.55; P=.035) in the regression analysis. In conclusion, OSA is
      independently associated with arterial stiffness and nondipping blood pressure in
      patients with hypertension regardless of sex.

PMID- 28429852
TI  - Anti-inflammatory and retinal protective effects of capsaicin on ischaemia
      induced injuries through the release of endogenous somatostatin.
AB  - The mechanisms regarding the retinal protective and anti-inflammatory effects of
      capsaicin (CAP) remain unclear. Somatostatin is contained in CAP-sensitive
      sensory neurons, including nerve terminals, from which it can be released by
      capsaicin. The present study provides a novel neurohumoral regulatory mechanism
      for CAP-induced-endogenous somatostatin in a retinal ischaemia-reperfusion (I/R)
      mouse model. CAP (0.5 mg/kg) was injected subcutaneously 5 minutes after I/R. A
      selective somatostatin-depleting agent, cysteamine, was applied subcutaneously 4
      hours before the experiment to examine the effects of endogenous somatostatin.
      Ischaemia and oxidative stress-induced inflammatory factors (CXCL10, CXCR3 and NF
      kappaB p65) were also examined in the present study. The morphometric evaluation
      showed that the retinal thickness was increased 24 hours after I/R injury and
      attenuated 7 days after I/R injury. The number of ganglion cells was reduced 7
      days after I/R injury. The application of CAP significantly prevented retinal I/R
      damage. Cysteamine pretreatment reversed the effects of CAP. Inhibition of
      CXCL10/CXCR3 and NF-kappaB (especially in astrocytes and microglia/macrophage)
      was involved in capsaicin-induced retinal protection through endogenous
      somatostatin. CAP has anti-inflammatory and neuroprotective effects in ischaemia
      induced retinal injuries through endogenous somatostatin. Novel therapeutic
      remedies for inflammation or neuronal injuries were developed based on the
      systemic humoral effects related to CAP.

PMID- 28429854
TI  - Application of 3C insulin pump system in combination with non-invasive
      ventilation in the treatment of a patient with type 2 diabetes and obstructive
      sleep apnea syndrome.
AB  - We observed the curative effect of the 3C insulin system in combination with non
      invasive ventilation in a patient with type 2 diabetes and obstructive sleep
      apnea syndrome (OSAS). The 3C insulin pump is a system of devices that closely
      monitors and effectively regulates blood glucose levels. Non-invasive ventilation
      has been shown to be an effective treatment for OSAS. A type 2 diabetes patient
      with concomitant OSAS was treated with a 3C insulin pump system for real-time
      continuous glucose monitoring and nocturnal non-invasive ventilation for OSAS.
      Treatment-induced diabetic remission with improved sleep and reduced hypoglycemic
      episodes was achieved. Therefore, the 3C insulin pump system, in combination with
      non-invasive ventilation, is an effective treatment for type 2 diabetes patients
      with concomitant OSAS.

PMID- 28429853
TI  - Molecular cloning of MDA5, phylogenetic analysis of RIG-I-like receptors (RLRs)
      and differential gene expression of RLRs, interferons and proinflammatory
      cytokines after in vitro challenge with IPNV, ISAV and SAV in the salmonid cell
      line TO.
AB  - The RIG-I receptors RIG-I, MDA5 and LGP2 are involved in viral recognition, and
      they have different ligand specificity and recognize different viruses.
      Activation of RIG-I-like receptors (RLRs) leads to production of cytokines
      essential for antiviral immunity. In fish, most research has focused on
      interferons, and less is known about the production of proinflammatory cytokines
      during viral infections. In this study, we have cloned the full-length MDA5
      sequence in Atlantic salmon, and compared it with RIG-I and LGP2. Further, the
      salmonid cell line TO was infected with three fish pathogenic viruses, infectious
      pancreatic necrosis virus (IPNV), infectious salmon anaemia virus (ISAV) and
      salmonid alphavirus (SAV), and differential gene expression (DEG) analyses of
      RLRs, interferons (IFNa-d) and proinflammatory cytokines (TNF-alpha1, TNF-alpha2,
      IL-1beta, IL-6, IL-12 p40s) were performed. The DEG analyses showed that the
      responses of proinflammatory cytokines in TO cells infected with IPNV and ISAV
      were profoundly different from SAV-infected cells. In the two aforementioned, TNF
      alpha1 and TNF-alpha2 were highly upregulated, while in SAV-infected cells these
      cytokines were downregulated. Knowledge of virus recognition by the host and the
      immune responses during infection may help elucidate why and how some viruses can
      escape the immune system. Such knowledge is useful for the development of immune
      prophylactic measures.

PMID- 28429855
TI  - Coincidence of mandibular fractures with isolated posterior maxillary sinus
      fractures.
AB  - BACKGROUND/AIM: There are no data available to show whether there is a
      relationship between mandibular fractures and isolated fractures of the posterior
      and/or lateral walls of the maxillary sinus. The aim of this study was to
      determine whether there is a coincidence between these fracture patterns.
      METHODS: Four hundred large volume cone beam computed tomography scans (CBCT) of
      patients with a fracture of the mandible between 2008 and 2013 were analyzed
      retrospectively. Patients with multiple midfacial fractures were excluded. The
      radiographic findings were correlated with epidemiological and clinical data of
      the patients such as gender, age, treatment methods, or complications. RESULTS:
      The most frequent fracture sites of the mandible were the jaw angle, the
      parasymphysis region, and the condyle. Nineteen of the 400 patients (4.75%) had
      an isolated fracture of the lateral and/or posterior maxillary sinus. Odds-ratio
      analysis revealed a high tendency for significant correlation of condylar process
      fractures with isolated maxillary sinus fractures. Chi-square test demonstrated a
      P-value near statistical significance (P=.054). No other fracture site of the
      mandible could be associated with an isolated fracture of the maxillary sinus.
      CONCLUSION: A condylar process fracture of the mandible after trauma without any
      further injury of the midface may be associated with an isolated fracture of the
      lateral and/or posterior maxillary sinus.

PMID- 28429856
TI  - Glycosyltransferase cascades for natural product glycosylation: Use of plant
      instead of bacterial sucrose synthases improves the UDP-glucose recycling from
      sucrose and UDP.
AB  - Natural product glycosylations by Leloir glycosyltransferases (GTs) require
      expensive nucleotide-activated sugars as substrates. Sucrose synthase (SuSy)
      converts sucrose and uridine 5'-diphosphate (UDP) into UDP-glucose. Coupling of
      SuSy and GT reactions in one-pot cascade transformations creates a UDP cycle,
      which regenerates the UDP-glucose continuously and so makes it an expedient donor
      for glucoside production. Here we compare SuSys with divergent kinetic
      characteristics for UDP-glucose recycling in the synthesis of the natural C
      glucoside nothofagin. Development of a fast reversed-phase ion-pairing HPLC
      method, quantifying all relevant reactants from the coupled conversion in a
      single run, was key to dissect the main factors of recycling efficiency.
      Limitations due to high KM , both for UDP and sucrose, were revealed for the
      bacterial SuSy from Acidithiobacillus caldus. The L637M-T640V double mutant of
      this SuSy with a 60-fold reduced KM for UDP substantially improved UDP-glucose
      recycling. The SuSy from Glycine max (soybean) was nevertheless the most active
      enzyme at the UDP (<= 0.5 mM) and sucrose (<= 1 M) concentrations used. It was
      also unexpectedly stable at up to 50 degrees C where spontaneous decomposition of
      UDP-glucose started to become problematic. The herein gained in-depth
      understanding of requirements for UDP-glucose regeneration supports development
      of efficient GT-SuSy cascades.

PMID- 28429857
TI  - NDUFA4L2 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis
      and mitochondrial dysfunction by inhibiting complex I.
AB  - Myocardial ischaemia/reperfusion (I/R) injury may cause the apoptosis of
      cardiomyocytes as well as mitochondrial dysfunction. The aims of the present
      study were to investigate whether NADH dehydrogenase 1 alpha subcomplex subunit 4
      like 2 (NDUFA4L2) on myocardial ischaemia-reperfusion (I/R) injury and the
      underlying molecular mechanism. The hypoxia-reperfusion (H/R) model was
      established in vitro using H9c2 cells to simulate I/R injury. NDUFA4L2 and
      complex I expression levels were detected using RT-PCR and western blot. The
      apoptosis of H9c2 cells was evaluated by flow cytometry and the expression of Bax
      and Bcl-2 was detected by western blot. The mitochondrial function was assessed
      by ATP concentration, mPTP opening and cytochrome c (cyto C) expression. Our data
      indicated that NDUFA4L2 expression was significantly down-regulated in myocardial
      H/R injury. Overexpression of NDUFA4L2 led to a dramatic prevention of H/R
      induced apoptosis accompanied by a decrease in the expression of Bax and an
      increase in the expression of Bcl-2. Meanwhile, augmentation of NDUFA4L2
      dramatically prevented mitochondrial dysfunction caused by H/R as reflecting in
      the increased ATP concentration, delayed mPTP opening, as well as down-regulated
      cyto C expression. Moreover, complex I activation was heightened and negatively
      regulated by NDUFA4L2. Silencing complex I conspicuously attenuated cell
      apoptosis and mitochondrial dysfunction. Taken together, our findings
      demonstrated that NDUFA4L2 protects against H/R injury by preventing myocardium
      apoptosis and mitochondrial dysfunction via the complex I, and may be a potential
      therapeutic approach for attenuating myocardial I/R injury.

PMID- 28429858
TI  - Trauma-Related Disgust in Veterans With Interpersonal Trauma.
AB  - Although traditionally conceptualized as an anxiety disorder, variability in
      posttraumatic stress disorder (PTSD) may be explained by individual differences
      in peri- or posttraumatic disgust. We examined relationships between disgust
      reactions and other trauma-related symptoms in 100 veterans with a history of
      interpersonal trauma and gender differences in these variables. We also evaluated
      the mediating role of posttraumatic disgust and guilt in the relationship between
      peritraumatic disgust and PTSD symptoms. Participants completed cross-sectional
      self-report questionnaires of trauma-related emotions, PTSD, and other
      psychological symptoms as part of clinical intake procedures. Women and men did
      not differ on trauma-related emotions or symptoms. However, the relationship
      between peri- and posttraumatic disgust depended on gender, with men reporting a
      stronger association between peri- and posttraumatic disgust than women (p =
      .013, DeltaR2 = .04). Posttraumatic disgust and guilt mediated the relationship
      between peritraumatic disgust and PTSD symptoms, controlling for gender (a1 a2 b1
      = 0.18, SE = 0.09, PM = .19). Our results converge with those found in other
      studies suggesting that disgust is a common trauma-related emotion and that men
      and women may experience differential relationships between peri- and
      posttraumatic emotional experiences. Further study of the role of trauma-related
      emotional responses in PTSD etiology and treatment is warranted.

PMID- 28429859
TI  - Aneurysms in neurofibromatosis type 2: Evidence for vasculopathy?
AB  - There have been anecdotal reports of vasculopathy associated with
      Neurofibromatosis Type 2 (NF2). Given the increasing use of bevacizumab, a
      vascular endothelial growth factor inhibitor which results in an increased risk
      of bleeding, it is important to ascertain if there is a predisposition to
      vascular abnormalities in NF2. In our unit NF2 patients undergo annual MRI brain
      and internal auditory meatus imaging. We noted incidental intracranial aneurysms
      in some patients and sought to determine the prevalence of intracranial aneurysms
      in our cohort of NF2 patients. We conducted a retrospective audit of the MRI
      images of 104 NF2 patients from 2014 to 2016. Axial T2 brain MRI images were
      assessed for vascular abnormalities by two neuroradiologists blinded to patient's
      clinical details. Intracranial aneurysms were detected in four patients and an
      aneurysm clip related to previous surgery was noted in one additional patient.
      Using standard MRI imaging sequences alone we provide evidence of intracranial
      aneurysms in 4.4% of our cohort. This compares with an estimated overall
      prevalence of 3% in the general population. We discuss these findings as well as
      other evidence for a vasculopathy associated with NF2.

PMID- 28429861
TI  - Extreme ocean acidification reduces the susceptibility of eastern oyster shells
      to a polydorid parasite.
AB  - Ocean acidification poses a threat to marine organisms. While the physiological
      and behavioural effects of ocean acidification have received much attention, the
      effects of acidification on the susceptibility of farmed shellfish to parasitic
      infections are poorly understood. Here we describe the effects of moderate (pH
      7.5) and extreme (pH 7.0) ocean acidification on the susceptibility of
      Crassostrea virginica shells to infection by a parasitic polydorid, Polydora
      websteri. Under laboratory conditions, shells were exposed to three pH treatments
      (7.0, 7.5 and 8.0) for 3- and 5-week periods. Treated shells were subsequently
      transferred to an oyster aquaculture site (which had recently reported an
      outbreak of P. websteri) for 50 days to test for effects of pH and exposure time
      on P. websteri recruitment to oyster shells. Results indicated that pH and
      exposure time did not affect the length, width or weight of the shells.
      Interestingly, P. websteri counts were significantly lower under extreme (pH 7.0;
      ~50% reduction), but not moderate (pH 7.5; ~20% reduction) acidification levels;
      exposure time had no effect. This study suggests that extreme levels - but not
      current and projected near-future levels - of acidification (?pH ~1 unit) can
      reduce the susceptibility of eastern oyster shells to P. websteri infections.

PMID- 28429860
TI  - Safety, tolerability and efficacy of lixisenatide in combination with oral
      antidiabetic treatment in Japanese patients with type 2 diabetes: An open-label,
      multicenter study.
AB  - AIM/INTRODUCTION: To assess the overall safety and efficacy of lixisenatide in
      combination with background oral antidiabetic drug treatment in Japanese patients
      with type 2 diabetes, as required by Japanese guidelines. MATERIALS AND METHODS:
      A phase 3, multicenter, uncontrolled, open-label, four-arm, parallel-group study
      of Japanese outpatients with type 2 diabetes was carried out; patients received
      once-daily lixisenatide in combination with biguanide, thiazolidinedione, alpha
      glucosidase inhibitors or glinide (NCT01940965). The primary end-point was safety
      over 52 weeks; secondary end-points included absolute change from baseline in
      glycated hemoglobin A1c at weeks 24 and 52. RESULTS: A total of 294 patients were
      enrolled (biguanide, thiazolidinedione, alpha-glucosidase groups: 73 patients
      each; glinide group: 75 patients). Overall, 90.4% of patients in the biguanide
      group, 83.6% in the thiazolidinedione group, 83.6% in the alpha-glucosidase group
      and 85.3% in the glinide group reported one or more treatment-emergent adverse
      event, the most common of which were nasopharingitis, nausea and constipation.
      Symptomatic hypoglycemia was reported in 5.5, 0, 1.4, and 10.7% of patients in
      the biguanide, thiazolidinedione, alpha-glucosidase and glinide groups,
      respectively. No severe hypoglycemia was observed. Hemoglobin A1c decreased from
      baseline at weeks 24 and 52, with mean changes ranging from -0.98 to -1.22%, and
      from -0.80 to -1.08%, respectively, across all groups. CONCLUSIONS: Lixisenatide
      treatment administered daily over 52 weeks was well tolerated and effective in
      improving glycemic control in Japanese patients with type 2 diabetes uncontrolled
      with existing oral antidiabetic drug therapies. The use of lixisenatide in
      combination with oral antidiabetic drugs is a valuable treatment option for
      Japanese patients with type 2 diabetes after failure of oral antidiabetic
      treatment alone.

PMID- 28429862
TI  - Epidemiology of invasive fungal diseases in children with solid tumours
      undergoing autologous haematopoietic stem cell transplantation: a 10-year
      experience in a tertiary Italian centre.
AB  - The objective of the study was to determine the incidence of invasive fungal
      disease (IFD) in children undergoing autologous haematopoietic stem cell
      transplantation (auHSCT) for solid tumours (ST). Retrospective study on auHSCT
      was performed in children with ST (January 2006-December 2015). Data on the
      number of patient-days at risk (pdr) during the first 30 and 90 days after auHSCT
      and cases of proven/probable IFDs were collected. Infection rate (IR,
      episodes/1000 pdr) and proportions and cumulative risk (CR) of IFD were
      evaluated. In 186 patients, 270 auHSCT were performed, for a total of 8327 pdr
      during the first 30 days and 24 366 up to day 90. Median age was 5 years
      (interquartile range 2;8), 63% were male. At day 30, seven procedures were
      complicated by IFD, with an IR of 0.84 (95% CI 0.66-1.02) and aCR of 2.6% (95% CI
      1.4-5.4) at 18 days after HSCT. Within day 90, two further IFDs were detected
      with an IR of 0.37 (95% CI -0.49 to 1.23) and a CR of 3.3% (95% CI 1.7-6.3) at
      day 69. Children undergoing auHSCT for ST have a low incidence of IFDs in the
      first 90 days after the procedure.

PMID- 28429863
TI  - Abdominal vagus nerve stimulation as a new therapeutic approach to prevent
      postoperative ileus.
AB  - BACKGROUND: Electrical stimulation of the cervical vagus nerve (VNS) prevents
      postoperative ileus (POI) in mice. As this approach requires an additional
      cervical procedure, we explored the possibility of peroperative abdominal VNS in
      mice and human. METHODS: The effect of cervical and abdominal VNS was studied in
      a murine model of POI and lipopolysaccharide (LPS)-induced sepsis. Postoperative
      ileus was quantified by assessment of intestinal transit of fluorescent dextran
      expressed as geometric center (GC). Next, the effect of cervical and abdominal
      VNS on heart rate was determined in eight Landrace pigs to select the optimal
      electrode for VNS in human. Finally, the effect of sham or abdominal VNS on LPS
      induced cytokine production of whole blood was studied in patients undergoing
      colorectal surgery. KEY RESULTS: Similar to cervical VNS, abdominal VNS
      significantly decreased LPS-induced serum tumor necrosis factor-alpha (TNFalpha)
      levels (abdominal VNS: 366+/-33 pg/mL vs sham: 822+/-105 pg/mL; P<.01). In line,
      in a murine model of POI, abdominal VNS significantly improved intestinal transit
      (GC: sham 5.1+/-0.2 vs abdominal VNS: 7.8+/-0.6; P<.01) and reduced intestinal
      inflammation (abdominal VNS: 35+/-7 vs sham: 80+/-8 myeloperoxidase positive
      cells/field; P<.05). In pigs, heart rate was reduced by cervical VNS but not by
      abdominal VNS. In humans, abdominal VNS significantly reduced LPS-induced IL8 and
      IL6 production by whole blood. CONCLUSIONS & INFERENCES: Abdominal VNS is
      feasible and safe in humans and has anti-inflammatory properties. As abdominal
      VNS improves POI similar to cervical VNS in mice, our data indicate that
      peroperative abdominal VNS may represent a novel approach to shorten POI in man.

PMID- 28429864
TI  - Have we been overestimating fall rates in Parkinson's disease?

PMID- 28429865
TI  - Differential effects of bleeds on the development of arthropathy - basic and
      applied issues.
AB  - Haemophilia is characterized by a spontaneous bleeding tendency, affecting mainly
      the synovial joints. Recurrent joint bleeds induce a cascade of inflammatory as
      well as degenerative processes injuring synovium, cartilage and bone. These
      processes affect each other and may occur in parallel and/or sequentially.
      Clinically, the effects of joint bleeds are heterogeneous. A marked variability
      in joint damage is observed in patients with a similar bleeding history. Also
      late stage effects differ with some patients developing chronic synovitis, and
      others suffering from osteochondral degeneration called haemophilic arthropathy.
      This article reviews the current understanding of the pathogenesis of blood
      induced joint damage, elaborates on potential explanations for the differential
      effects of a bleed, and discusses challenges for future research.

PMID- 28429866
TI  - Successful multiple organ donation after donor brain death due to Actinomyces
      israelii meningitis.
AB  - The increasing gap between availability of solid organs for transplantation and
      the demand has led to the inclusion of donor organs that, according to current
      guidelines, may be discarded, some of them because of the possibility for
      transmission of infection to the recipients. We present the first report, to the
      best of our knowledge, of a case of a brain-dead donor with a localized and
      treated Actinomyces israelii central nervous system infection who, after a
      thorough evaluation, provided organs for successful transplant procedures in four
      recipients. There was no evidence of transmission of infection within a 6-month
      follow-up. Relative contraindications must be individualized in order to expand
      the number of real organ donors, emphasizing caution in rare causes for brain
      death in which patients should be thoroughly evaluated for possible donation.

PMID- 28429867
TI  - Health-related quality of life questionnaires in individuals with haemophilia: a
      systematic review of their measurement properties.
AB  - BACKGROUND: The evaluation of health related quality of life (HRQOL) is essential
      for a full assessment of the influence of an illness on patients' lives. The aim
      of this paper is to critically appraise and compare the measurement properties of
      HRQOL questionnaires studied in haemophilia. METHODS: Bibliographic databases
      (Embase, Medline, Cinahl and PsycInfo) were searched for articles evaluating
      measurement properties of HRQOL questionnaires in haemophilia. Articles were
      excluded that did not report HRQOL measurement properties, or when <50% of the
      study population had haemophilia. The methodological quality of the selected
      studies was evaluated using the COSMIN checklist. The measurement properties of
      the HRQL questionnaires were rated as 'positive', 'indeterminate' or 'negative',
      accompanied by levels of evidence. RESULTS: The search resulted in 1597 unique
      hits, of which 22 studies were included. These articles evaluated three
      questionnaires for children (CHO-KLAT, Haemo-QoL and one unnamed measure) and
      five for adults (Hemofilia-QoL, Haemophilia Well-Being Index, HAEMO-QoL-A, Haem-A
      QoL, and SF-36). The CHO-KLAT was the paediatric measure that showed the
      strongest measurement properties in high-quality studies. The Haemophilia Well
      Being Index and HAEMO-QoL-A performed best among the adult measures. None of the
      studies reported measurement error and responsiveness. CONCLUSION: Our findings
      suggest that there is no need for new disease-specific HRQOL questionnaires for
      haemophilia, but rather that additional research is necessary to document the
      measurement properties of the currently available questionnaires, specifically
      focusing on the structural validity, measurement error and responsiveness of
      these questionnaires.

PMID- 28429868
TI  - Clarification of serotonin-induced effects in peripheral artery disease observed
      through the femoral artery response in models of diabetes and vascular occlusion:
      The role of calcium ions.
AB  - Recent findings have demonstrated that serotonin is an important participant in
      the development and progression of peripheral artery diseases. Taking this into
      consideration, the goals of this study were to investigate the effects of
      serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic
      animals, with and without artery occlusion, with a particular focus on
      determining the role of calcium in this process. Contraction experiments with
      serotonin on intact and denuded femoral artery rings, in the presence or absence
      of nifedipine and ouabain (both separately, or in combination), as well as Ca2+ 
      free Krebs-Ringer bicarbonate solution were performed. The serotonin-induced
      results were concentration dependent, but only in healthy animals. The
      endothelium-dependent contraction of the femoral artery was assessed. In healthy
      animals, the endothelium-reliant part of contraction was dependent on the
      extracellular calcium, while the smooth muscle-related part was instead dependent
      on the intracellular calcium. In diabetic animals, both nifedipine and ouabain
      influenced serotonin-induced vascular effects by blocking intracellular calcium
      pathways. However, this was diminished after the simultaneous administration of
      both blockers.

PMID- 28429869
TI  - Importance of prenatal care in reducing stillbirth.

PMID- 28429870
TI  - Induction of Axial Chirality in 8-Arylquinolines through Halogenation Reactions
      Using Bifunctional Organocatalysts.
AB  - The enantioselective syntheses of axially chiral heterobiaryls were accomplished
      through the aromatic electrophilic halogenation of 3-(quinolin-8-yl)phenols with
      bifunctional organocatalysts that control the molecular conformations during
      successive halogenations. Axially chiral quinoline derivatives, which have rarely
      been synthesized in an enantioselective catalytic manner, were afforded in
      moderate-to-good enantioselectivities through bromination, and an analogous
      protocol also enabled enantioselective iodination. In addition, this catalytic
      reaction, which allows enantioselective control through the use of mono-ortho
      substituted substrates, allowed the asymmetric synthesis of 8-arylquinoline
      derivatives bearing two different halogen groups in high enantioselectivities.

PMID- 28429871
TI  - Potentiation of Antibiotic against Psedomonas aeruginosa biofilm: A study with
      Plumbagin and Gentamicin.
AB  - AIM: Pseudomonas aeruginosa is one of the fatal biofilm forming pathogens which
      pose to be a problem in clinical infections, contamination of food and marine
      ecosystems. In this report a napthoquinone - Plumbagin has been explored for its
      antimicrobial (antibacterial and antibiofilm) activity against P. aeruginosa
      biofilm. The ability of Plumbagin to enhance the bioactivity of a known broad
      spectrum antibiotic was further assayed by combining the sub-MIC doses of
      Plumbagin with sub-MIC doses of Gentamicin against P. aeruginosa biofilm. METHODS
      AND RESULTS: This combinatorial approach was used for a series of experiments for
      understanding the mechanism of action for antibiofilm activity against P.
      aeruginosa (MTCC424, MTCC2488). Antibiofilm activity was studied by safranin
      staining, estimating total protein, visualisation of biofilms and EPS
      quantification. Antivirulent activity of these doses was studied by azocasein
      degradation, expression of virulent factors and molecular docking. Expression of
      quorum sensing (QS) phenotypes was studied by motility assessment and mRNA
      expression pattern of virulence genes. It was observed that Plumbagin alone and
      the combinatorial doses of Plumbagin and Gentamicin exhibit significant
      antibiofilm and antivirulent activity coupled with the reduction in expression of
      QS phenotypes and virulence genes. Molecular docking study revealed that
      Plumbagin had variable affinity for different QS proteins. CONCLUSION: Low doses
      of Plumbagin and Gentamicin exhibit synergistic activity against P. aeruginosa
      biofilm whilst maintaining their effectiveness This article is protected by
      copyright. All rights reserved.

PMID- 28429872
TI  - Liraglutide effect on epicardial fat: Missing the forest for the trees.

PMID- 28429873
TI  - Sucrose transporters and plasmodesmal regulation in passive phloem loading.
AB  - An essential step for the distribution of carbon throughout the whole plant is
      the loading of sugars into the phloem in source organs. In many plants,
      accumulation of sugars in the sieve element-companion cell (SE-CC) complex is
      mediated and regulated by active processes. However, for poplar and many other
      tree species, a passive symplasmic mechanism of phloem loading has been proposed,
      characterized by symplasmic continuity along the pre-phloem pathway and the
      absence of active sugar accumulation in the SE-CC complex. A high overall leaf
      sugar concentration is thought to enable diffusion of sucrose into the phloem. In
      this review, we critically evaluate current evidence regarding the mechanism of
      passive symplasmic phloem loading, with a focus on the potential influence of
      active sugar transport and plasmodesmal regulation. The limited experimental
      data, combined with theoretical considerations, suggest that a concomitant
      operation of passive symplasmic and active phloem loading in the same minor vein
      is unlikely. However, active sugar transport could well play an important role in
      how passively loading plants might modulate the rate of sugar export from leaves.
      Insights into the operation of this mechanism has direct implications for our
      understanding of how these plants utilize assimilated carbon.

PMID- 28429874
TI  - An International Prophylaxis Study Group (IPSG) survey of prophylaxis in adults
      with severe haemophilia.

PMID- 28429875
TI  - Effect of untreated zirconium oxide nanofiller on the flexural strength and
      surface hardness of autopolymerized interim fixed restoration resins.
AB  - OBJECTIVE: Autopolymerized poly methyl methacrylate (PMMA) resin is commonly used
      for the construction of interim restorations; however, it has less than optimal
      mechanical properties. In this article, we evaluated the reinforcing effect of
      adding untreated zirconia nanoparticles on the flexural strength and surface
      hardness of this resin. METHODS: A total of 80 specimens were fabricated. Forty
      each were used for the flexural strength test and for the surface hardness test.
      The specimens were categorized into four groups of 10 specimens each as follows:
      pure PMMA, PMMA with 1%, PMMA with 2.5%, and PMMA with 5% weight of untreated
      zirconia nanofillers. The flexural strength of the specimens was evaluated by the
      three-point bending test, and the surface hardness was assessed by micro Vickers
      hardness test. The data obtained from these tests were statistically analyzed
      using one-way ANOVA and Tukey tests. In addition, the fracture surface
      characteristics were assessed using scanning electron microscopy. RESULTS:
      Flexural strength testing showed a significant increase in the group with 2.5%
      zirconia nanofillers, but not in the groups with 1% and 5% nanofillers. Surface
      hardness was also significantly increased in the groups with 2.5% and 5%
      nanofillers, but not in the 1% group. The SEM images showed a highly brittle
      fracture in the pure PMMA group and noticeably less brittle fracture in the group
      with PMMA with 2.5% weight of zirconia nanofillers. Several cracks and void were
      also observed in the group with 5% weight of nanofillers. CONCLUSION:
      Reinforcement of the autopolymerized acrylic resin with 2.5% weight of untreated
      zirconia nanofillers significantly increased its flexural strength and surface
      hardness. CLINICAL SIGNIFICANCE: The interim restorations play an important role
      in protection of hard and soft oral tissue and providing the critical function
      and esthetics before the final restoration replacing. Temporary restorations must
      have sufficient flexural strength to resist deformation during mastication force.
      Moreover, sufficient surface hardness is also necessary to resist abrasion. The
      color stability of materials is considered as an important clinical criterion,
      specifically in esthetics zone. Several materials have been applied to improve
      ?the flexural strength and surface hardness for representing clinical success.
      Zirconia nanoparticles show desirable features, such as high hardness,
      biocompatibility, and favorable color because of its white color. ?It seems that
      the addition of the nano zirconia to acrylic resins can be the appropriate method
      for improving interim restoration.

PMID- 28429876
TI  - Iodine-131-meta-iodobenzylguanidine therapy for patients with newly diagnosed
      high-risk neuroblastoma.
AB  - BACKGROUND: Patients with newly diagnosed high-risk (HR) neuroblastoma (NBL)
      still have a poor outcome, despite multi-modality intensive therapy. This poor
      outcome necessitates the search for new therapies, such as treatment with 131I
      meta-iodobenzylguanidine (131I-MIBG). OBJECTIVES: To assess the efficacy and
      adverse effects of 131I-MIBG therapy in patients with newly diagnosed HR NBL.
      SEARCH METHODS: We searched the following electronic databases: the Cochrane
      Central Register of Controlled Trials (CENTRAL; the Cochrane Library 2016, Issue
      3), MEDLINE (PubMed) (1945 to 25 April 2016) and Embase (Ovid) (1980 to 25 April
      2016). In addition, we handsearched reference lists of relevant articles and
      reviews. We also assessed the conference proceedings of the International Society
      for Paediatric Oncology, Advances in Neuroblastoma Research and the American
      Society of Clinical Oncology; all from 2010 up to and including 2015. We scanned
      the International Standard Randomized Controlled Trial Number (ISRCTN) Register
      (www.isrctn.com) and the National Institutes of Health Register for ongoing
      trials (www.clinicaltrials.gov) on 13 April 2016. SELECTION CRITERIA: Randomised
      controlled trials (RCTs), controlled clinical trials (CCTs), non-randomised
      single-arm trials with historical controls and cohort studies examining the
      efficacy of 131I-MIBG therapy in 10 or more patients with newly diagnosed HR NBL.
      DATA COLLECTION AND ANALYSIS: Two review authors independently performed the
      study selection, risk of bias assessment and data extraction. MAIN RESULTS: We
      identified two eligible cohort studies including 60 children with newly diagnosed
      HR NBL. All studies had methodological limitations, with regard to both internal
      (risk of bias) and external validity. As the studies were not comparable with
      regard to prognostic factors and treatment (and often used different outcome
      definitions), pooling of results was not possible. In one study, the objective
      response rate (ORR) was 73% after surgery; the median overall survival was 15
      months (95% confidence interval (CI) 7 to 23); five-year overall survival was
      14.6%; median event-free survival was 10 months (95% CI 7 to 13); and five-year
      event-free survival was 12.2%. In the other study, the ORR was 56% after
      myeloablative therapy and autologous stem cell transplantation; 10-year overall
      survival was 6.25%; and event-free survival was not reported. With regard to
      short-term adverse effects, one study showed a prevalence of 2% (95% CI 0% to
      13%; best-case scenario) for death due to myelosuppression. After the first cycle
      of 131I-MIBG therapy in one study, platelet toxicity occurred in 38% (95% CI 18%
      to 61%), neutrophil toxicity in 50% (95% CI 28% to 72%) and haemoglobin toxicity
      in 69% (95% CI 44% to 86%); after the second cycle this was 60% (95% CI 36% to
      80%) for platelets and neutrophils and 53% (95% CI 30% to 75%) for haemoglobin.
      In one study, the prevalence of hepatic toxicity during or within four weeks
      after last the MIBG treatment was 0% (95% CI 0% to 9%; best-case scenario).
      Neither study reported cardiovascular toxicity and sialoadenitis. One study
      assessed long-term adverse events in some of the children: there was elevated
      plasma thyroid-stimulating hormone in 45% (95% CI 27% to 65%) of children; in all
      children, free T4 was within the age-related normal range (0%, 95% CI 0% to 15%).
      There were no secondary malignancies observed (0%, 95% CI 0% to 9%), but only
      five children survived more than four years. AUTHORS' CONCLUSIONS: We identified
      no RCTs or CCTs comparing the effectiveness of treatment including 131I-MIBG
      therapy versus treatment not including 131I-MIBG therapy in patients with newly
      diagnosed HR NBL. We found two small observational studies including chilren.
      They had high risk of bias, and not all relevant outcome results were available.
      Based on the currently available evidence, we cannot make recommendations for the
      use of 131I-MIBG therapy in patients with newly diagnosed HR NBL in clinical
      practice. More high-quality research is needed.

PMID- 28429877
TI  - Normal-weight obesity and cardiometabolic risk: A 7-year longitudinal study in
      girls from prepuberty to early adulthood.
AB  - OBJECTIVE: To study whether normal-weight obesity in childhood is associated with
      increased cardiometabolic risk in early adulthood. METHODS: This study assessed
      data for 236 girls followed from prepuberty to early adulthood. Growth chart data
      were obtained from birth to 18 years. Body composition was assessed by dual
      energy x-ray absorptiometry and cardiometabolic risk by calculating continuous
      clustered risk score (at ages 11, 14, and 18). The association of body weight
      status with cardiometabolic risk from childhood to early adulthood was examined.
      RESULTS: Subjects with normal-weight obesity were virtually indistinguishable
      from their normal-weight lean peers in terms of relative body weight and BMI but
      had significantly higher fat mass (7.1-7.3 kg) and cardiometabolic risk already
      in childhood, and this difference persisted into early adulthood (P <  0.001 for
      all). CONCLUSIONS: Children and adolescents with normal body weight and high body
      fat percentage may be at increased risk for cardiometabolic morbidity in
      adulthood. Body fatness may be of utility in clinical practice to effectively
      identify children and adolescents at risk and to permit recommendation of
      lifestyle changes that could translate to lower risks of cardiovascular diseases
      in the future.

PMID- 28429878
TI  - A systematic review of ultrasound imaging as a tool for evaluating haemophilic
      arthropathy in children and adults.
AB  - The purpose of this study was to semi-quantitatively assess the evidence on the
      value of ultrasound (US) for assessment of haemophilic arthropathy (HA) in
      children and adults based on the following questions: (1) Does early diagnosis of
      pathological findings, using available US techniques, impact the functional
      status of the joint? (2) Do current available US techniques have the ability to
      accurately detect pathological changes in target joints in haemophilic patients?
      (3) Does treatment (prophylaxis) improve US evidence of haemophilic arthropathy
      in children and adults? (4) Is there any association between various US scoring
      systems and other clinical/radiological constructs? Of the 6880 citations
      identified searching databases such as MEDLINE, Embase, CENTRAL and Web of
      Science, 20 articles investigating either the diagnostic accuracy of US and/or US
      scanning protocols and scoring systems for assessment of HA met the inclusion
      criteria for the study. Of these, 14 articles evaluating the diagnostic accuracy
      of US were assessed by two independent reviewers for reporting quality using the
      Standards for Reporting of Diagnostic Accuracy (STARD) tool and for
      methodological quality using the Quality Assessment of Diagnostic Accuracy
      Studies 2 (QUADAS-2) tool. Using STARD, 1/14 studies (7%) was scored as of high
      reporting quality and 8/14 (57%), of moderate quality. Assessment with QUADAS-2
      reported 2/14 (14%) studies as having high methodological quality and 6/14 (43%)
      as having moderate quality. There is fair evidence (Grade B) to recommend US as
      an accurate technique for early diagnosis of HA, to demonstrate that US scores
      correlate with clinical/US constructs and to prove an association between US
      findings and functional status of the joint. However, there is insufficient
      evidence (Grade I) to conclude that US-detectable findings in HA are sensitive to
      changes in therapy.

PMID- 28429879
TI  - The pursuit of accurate blood pressure measurement: A 35-year travail.

PMID- 28429880
TI  - 'Extraction dermoscopy' as a rapid and innovative diagnostic tool for eruptive
      vellus hair cyst.

PMID- 28429881
TI  - Have we been overestimating fall rates in Parkinson's disease?

PMID- 28429882
TI  - Reply to the letter by Iorio.

PMID- 28429884
TI  - In defence of pH.

PMID- 28429883
TI  - Older adults' attitudes toward depression screening in primary care settings and
      exploring a brief educational pamphlet.
AB  - OBJECTIVES: This study aimed to assess older adults' (OAs') attitudes toward
      depression screening in primary care settings with a survey and explore the
      impact of an educational pamphlet on these attitudes. METHODS: Older adults above
      age 55 (N = 140) were randomly stratified by sex to an intervention or control
      group. The study included a baseline assessment, posttest, the Geriatric
      Depression Scale-Short Form, a two-page pamphlet on health and mood, and a 10
      question quiz. RESULTS: On the basis of survey responses, most participants
      (93.6%) were willing to complete a depression screen at their doctor's office,
      and 92.1% perceived depression screening as valuable to their health care.
      Participants rated the Geriatric Depression Scale-Short Form positively. The
      survey also provided information on how screening could be conducted in primary
      care settings to maximize OAs' comfort. Participants preferred screening in the
      waiting room or examination room instead of the nurse's station. Those receiving
      the pamphlet became significantly more willing to be screened for depression than
      those who did not, F(1, 134) = 4.47, p = 0.04. CONCLUSION: Most OAs appear
      receptive to completing a depression screen in primary care settings. Educating
      OAs about the value of depression screening and tailoring recognition systems to
      account for preferences may be an initial step in improving recognition rates.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28429885
TI  - Intravenous self-administration of benzydamine, a non-steroidal anti-inflammatory
      drug with a central cannabinoidergic mechanism of action.
AB  - Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical
      treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is
      known about the central pharmacological actions of BZY. Yet there are reports of
      voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric,
      hallucinatory state. In the present study, we investigated the reinforcing
      properties of BZY in a rat self-administration paradigm. We found that BZY has a
      powerful reinforcing effect and that this effect is greatly facilitated in
      animals that already had substance experience, having previously self
      administered heroin and cocaine, indicating cross sensitization between BZY and
      other common drugs of abuse. We then assessed the effect of BZY on prelimbic
      cortex-to-nucleus accumbens glutamatergic transmission, using field recordings in
      rat parasagittal brain slices. BZY dose-dependently reduced both field excitatory
      post synaptic potential amplitude and paired pulse ratio, suggesting a
      presynaptic mechanism of action. Similarly to the in vivo paradigm, also the
      electrophysiological effects of BZY were potentiated in slices from animals that
      had undergone cocaine and heroin self-administration. Furthermore, BZY-induced
      Long Term Depression (LTD)-like responses in the prelimbic cortex-to-nucleus
      accumbens circuitry were significantly reduced in the presence of the CB1
      receptor antagonist AM251. These findings provide firm evidence of the abuse
      liability of BZY and suggest a possible cannabinoidergic mechanism of action.
      Further research is needed in order to give insights into the molecular mechanism
      underlying BZY psychoactive and reinforcing effects, to better understand its
      abuse potential.

PMID- 28429886
TI  - Patients' experiences of consultations with physician associates in primary care
      in England: A qualitative study.
AB  - BACKGROUND: Physician associates are new to English general practice and set to
      expand in numbers. OBJECTIVE: To investigate the patients' perspective on
      consulting with physician associates in general practice. DESIGN: A qualitative
      study, using semi-structured interviews, with thematic analysis. SETTING AND
      PARTICIPANTS: Thirty volunteer patients of 430 who had consulted physician
      associates for a same-day appointment and had returned a satisfaction survey, in
      six general practices employing physician associates in England. FINDINGS: Some
      participants only consulted once with a physician associate and others more
      frequently. The conditions consulted for ranged from minor illnesses to those
      requiring immediate hospital admission. Understanding the role of the physician
      associate varied from 'certain and correct' to 'uncertain', to 'certain and
      incorrect', where the patient believed the physician associate to be a doctor.
      Most, but not all, reported positive experiences and outcomes of their
      consultation, with some choosing to consult the physician. Those with negative
      experiences described problems when the limits of the role were reached,
      requiring additional GP consultations or prescription delay. Trust and confidence
      in the physician associate was derived from trust in the NHS, the general
      practice and the individual physician associate. Willingness to consult a
      physician associate was contingent on the patient's assessment of the severity or
      complexity of the problem and the desire for provider continuity. CONCLUSION:
      Patients saw physician associates as an appropriate general practitioner
      substitute. Patients' experience could inform delivery redesign.

PMID- 28429888
TI  - Response to "Liraglutide effect on epicardial fat: Missing the forest for the
      trees".

PMID- 28429887
TI  - Effects of Aluminium on Long-Term Memory in Rats and on SIRT1 Mediating the
      Transcription of CREB-Dependent Gene in Hippocampus.
AB  - Epidemiological investigations have shown that aluminium (Al) is an important
      neurotoxicant which can be absorbed by organisms via various routes. Previous
      studies have confirmed that exposure to Al could cause neurodegenerative
      diseases, decline CREB phosphorylation and then down-regulate the transcription
      and protein expression of its target genes including BDNF. However, recent
      studies revealed that CREB activation alone was far from enough to activate the
      expression of long-term memory (LTM)-related genes; there might be other
      regulatory factors involved in this process. Several studies showed that TORC1
      might be involved in regulating the transcription of downstream target genes as
      well. Also, TORC1 could be mediated by SIRT1 during the formation of LTM.
      However, the role of CREB regulating system in Al-induced LTM impairment was
      still not utterly elucidated till now. This study was designed to establish the
      rat model of subchronic Al exposure to observe the neuroethology, regulatory
      factor levels and molecular biological alterations in hippocampal cells. The
      results showed that, with the increasing AlCl3 dose, blood Al content increased
      gradually; morphology of the hippocampus and neuronal ultrastructure were
      aberrant; in the Morris water maze test, the escape latency and distance
      travelled became longer, swimming traces turned more complicated in the place
      navigation test; intracellular Ca2+ , cAMP levels declined significantly in AlCl3
      -treated rats, followed by abated nuclear translocation of TORC1 and decreased
      SIRT1, TORC1 and pCREB levels. These results indicate that SIRT1 and TORC1 might
      play an important mediating role in Al-induced LTM impairment.

PMID- 28429889
TI  - Omentin treatment of epicardial fat improves its anti-inflammatory activity and
      paracrine benefit on smooth muscle cells.
AB  - OBJECTIVE: Epicardial adipose tissue (EAT) in coronary artery disease is insulin
      resistant and has a proinflammatory profile. This study examined the regulation
      of EAT by exogenous omentin and its consequence on vascular cells. METHODS:
      Stromal vascular cells (SC) of EAT and subcutaneous adipose tissue (SAT) from
      patients who underwent heart surgery were cultured and exposed to adipogenic
      factors with or without omentin. Proinflammatory cytokine regulation by omentin
      was analyzed in SC and mature adipocytes. Glucose uptake by EAT and SAT explants
      was determined after insulin, omentin, or combined treatment. Human vascular
      cells were exposed to secretomes of SC, with and without omentin treatment.
      Migration of smooth muscle cells and expression of adhesion molecules were
      determined by wound healing or real-time polymerase chain reaction, respectively.
      RESULTS: Omentin treatment raised adipogenesis-induced adiponectin levels on SC
      of EAT and reduced TNF-alpha expression levels (0.58 +/- 0.14-fold change; P =
      0.034) in mature adipocytes. Omentin improved the insulin activity of EAT and SAT
      explants from cardiovascular disease patients. Finally, secretomes of SC under
      omentin treatment reduced the migration of smooth muscle cells. CONCLUSIONS:
      Exogenous omentin might support a cardioprotective role through its effect on EAT
      regarding glucose uptake, anti-inflammatory response, and its paracrine role on
      smooth muscle cells.

PMID- 28429890
TI  - Prevalence of the reversed halo sign in neutropenic patients compared with non
      neutropenic patients: Data from a single-centre study involving 27 patients with
      pulmonary mucormycosis (2003-2016).
AB  - Pulmonary mucormycosis (PM) is a life-threatening infection and the diagnosis can
      be challenging. The objective was to retrospectively explore the value of the RHS
      in our cohort of 27 patients with mucormycosis and its relation to neutropenia.
      This was a retrospective study including all patients with a diagnosis of
      probable or proven invasive PM according to the 2008 EORTC/MSG criteria between
      September 2003 to April 2016. Fisher's exact test and Mann-Whitney test, with a P
      value statistically significant under .05 (P<.05), were used to compare
      neutropenic and non-neutropenic groups. 27 patients were eligible. The RHS could
      be identified in 78% of cases in the neutropenic group, and was less common in
      the non-neutropenic group (31%) (P<.05). Reticulations inside ground-glass
      opacity in case of RHS were present in 13 out of 15 patients (87%). Mucorales DNA
      detection by PCR on serum provided, a median time to the first PCR-positive
      sample of 3 days (-33 to +60 days) before diagnosis was confirmed. Six patients
      had IPA co-infection. In conclusion, RHS is more frequent in case of PM in
      neutropenic patients compare to non-neutropenic patients. Its presence in
      immunocompromised patients should be sufficient to promptly start Mucorales
      active antifungal treatment, while its absence especially in non-neutropenic
      cases should not be sufficient to exclude the diagnosis.

PMID- 28429891
TI  - Comparison of immunization rates of adults ages 65 years and older managed within
      two nurse practitioner-owned clinics with national immunization rates.
AB  - BACKGROUND AND PURPOSE: Adults ages >=65 years are at increased risk for
      infectious diseases. Ensuring these individuals are fully vaccinated is
      imperative. The purpose of this study was to assess the immunization rates of
      adults ages >=65 years managed by nurse practitioners (NPs) and compare the
      results with national immunization rates and Healthy People 2020 goals. METHODS:
      A convenience sample of adults ages >=65 years was obtained from two NP-managed
      clinics. The vaccine records of each subject were reviewed for documentation of
      having received five vaccines (tetanus, diphtheria, and pertussis; influenza;
      pneumococcal polysaccharide vaccine 23; pneumococcal conjugate vaccine 13; and
      herpes zoster vaccine). CONCLUSIONS: One hundred and fifty females (70.8%) and 62
      males (29.2%) met inclusion criteria. NP-managed patients had higher immunization
      rates than the national averages across all five major vaccines. The herpes
      zoster vaccination rates exceeded the recommendations from Healthy People 2020
      whereas pneumococcal and influenza rates were below. IMPLICATIONS FOR PRACTICE:
      The stocking of vaccines within the NP-managed clinics, direct billing to
      Medicare for Part D vaccines, and previsit care planning likely contributed to
      the high vaccination rates. These high immunization rates in patients managed by
      NPs provide support for the important role that NPs play in the care of older
      adults.

PMID- 28429892
TI  - Editorial Considerations on the "Manifesto for a Post-Mate-rialist Science".

PMID- 28429893
TI  - Significant associations between C-reactive protein levels, body adiposity
      distribution and peripheral blood cells in school-age children.
AB  - Obesity is associated with a state of chronic low-grade inflammation. Ge-
      nerally, there are significant correlations between body mass index and increased
      C-reactive protein levels. We investigated the relationship of high sensitivity C
      reactive protein (hsCRP) levels with body adiposity distribution and blood cell
      count in obese children. A cross-sec- tional study was performed in 225 Mexican
      children. In the study were included 106 obese and 119 normal-weight children,
      aged 6-13 years old. The body composition was evaluated by BMI, body
      circumferences and skinfold thickness. hsCRP levels and hematological para-
      meters were analyzed in all children. The hsCRP levels were higher in obese
      children than in the control group (1.5 and 0.41 mg/L respectively, P<0.001).
      Interestingly, hsCRP levels >3 mg/L were associated with the increase of
      circumferences of the waist, hip and arms (ORs= 9.08, 6.78 and 8.73,
      respectively, P<0.001), and,a higher thickness of triceps, subscapular and
      suprailiac skinfolds (ORs= 4.73, 6.39 and 5.26, respectively, P=0.001), as well
      as a higher leukocyte and platelet counts. The data suggest that hsCRP levels are
      associated with skinfold thickness and body circumferences, and a moderate
      relationship was found with leukocyte and Dlatelet counts in the studied
      children.

PMID- 28429894
TI  - Cytokine and metalloproteinases in gingival fluid from patients with chronic
      periodontitis.
AB  - The purpose of the present research was to determine the levels of IL- 1a, IL- 1
      P, TNF-a, IL-6, IL-6sR, IL-8, IL-10, MMP-3 and EMP-8 in gingival crevicular fluid
      (GCF) of subjects with chronic periodontitis. Clinical measurements were carried
      out in 20 patients with chronic periodontitis and 11 periodontally healthy
      controls. The clinical indexes evalua- ted were: gingival index (GI), plaque
      index (PI), bleeding on probing (BOP), probing depth (PD) and clinical attachment
      loss (CAL); the measurements were taken at six sites per tooth in all teeth in
      each subject. GCF samples were taken from one tooth per quadrant, and the levels
      of mediators were measured using an ELISA test. Statistically significant
      differences were observed between patients and control group in relation to all
      clinical parameters evaluated (p<0.05). The gingival concentrations, in pg/mL, of
      IL-la (patients: 239.06 +/- 65.5 vs control: 97.79 +/- 15.81), IL-10 (patients:
      157.19 +/- 36.4 vs control: 63.44 +/- 19.04), TNF-a (patients: 10.87 +/- 1.7 vs
      control: 1.15 +/- 0.84), IL-6 (patients: 3.77 +/- 1.7 vs control: 0.43 +/- 0.22),
      IL-6Sr (patients: 655.59 +/- 185.8 vs control: 73.59 +/- 23.18), IL-8 (patients:
      496.3 +/- 155.3 vs control: 206.13 +/- 46.63), IL-10 (patients: 10.75 +/- 3.6 vs
      control: 2.41 +/- 0.57), MMP-3 (patients: 3531 +/- 1558.2 vs control: 724.84 +/-
      289.51) and MMiP-8 (patients: 8231.70 +/- 1279.2 vs control: 1534.67+/- 814.90)
      were significantly greater in patients with periodontal disease than in the
      control group (p<0.00 1). The higher levels of the cytokines and
      metalloproteinases obtained in this study were significantly associated with the
      severity of the periodontal disease.

PMID- 28429895
TI  - Interleukin-6 and resistin in relation to anthropometric measurements in school
      children.
AB  - The worldwide prevalence of childhood obesity has increased greatly over the past
      three decades. The increasing occurrence in children of disorders, such as type 2
      diabetes, is believed to be a consequence of this obesity epidemic. Although the
      precise mechanisms are still unclear, dysregulated production or secretion of
      adipokines caused by excess adipose tissue and adipose tissue dysfunction can
      contribute to the development of obesity-related me- tabolic diseases. The
      objective of the study was to determine the serum levels of interleukin-6 and
      resistin in relation to anthropometric measurements in school children. One
      hundred and three school-age children were studied. The anthropometric assessment
      included weight, hei- ght, triceps skinfold (TSF), waist circumference (WC),
      waist-to-height ratio (WiHtR) and Body Mass Index (BMI). Interleukin-6 and
      resistin levels were measured by ELISA. The data were analyzed using the SPSS
      version 20 statistical program and 95% CIs (p<0.05) was considelred significant.
      BMI values indicated that 15.54 % of the population was overweight, and 11.65 %
      was obese. We found that scholars with excess WC, WHtR and BMI (overweight) had
      higher levels of IL-6 and scholars with excess WC and WHtR had higher levels of
      resistin (p <0.05). Interleukin-6 showed positive correlation with WC (r=0.229; p
      = 0.020) and waist-to-height ratio (r=0.397; p<O.OO1); and resistin with waist-to
      height ratio (r=0.283; p= 0.004). These results suggest that WC and waist-to
      height ratio are good anthropometric indicators in school children, contributing
      to early detection and prognosis of metabolic risks in children, due to their
      positive correlation with pro-inflammatory cytokines (interleukin-6 and
      resistin).

PMID- 28429896
TI  - Production of a conjugate between the rK346 antigen from Leishmania infantum and
      the horseradish peroxidase C for the detection of rK346 antibodies.
AB  - It was designed and characterized a reporter system to be captured by an-
      tibodies bound to ELISA plates. The system was designed with the rK346 from
      Leishmania infantum, a highly antigenic and specific protein. The rK346 was
      coupled to the horseradish peroxidase C (HRPc) from Armoracia rusticana using
      glutaraldehyde or sulfo-SMCC. Gluta- raldehyde conjugation was performed in two
      steps. Separation of conjugates was carried out using a Sepharose S-200 in size
      exclusion chromatography (SEC); fractions were analyzed via HRPc activity and
      through ELISA plates sensitized with polyclonal anti-rK346 IgG puri- fied from
      rabbit serum. A heterogeneous population of conjugates rK346-HRPc was obtained
      with molecular weights ranging between 109.7 +/- 16.5 to 67.6 +/- 10.1 kDa; with
      rK346-HRPe stoichiometries of 1:2; 2:1; 3:1; and 2:2. Conjugation using sulfo
      SMCC was carried out first by introducing -SH groups onto the HRPc using the SATA
      reagent and the antigen was modi- fied with sulfo-SMCC during 45 min. Separation
      and analysis of conjugates was performed similarly as with glutaraldehyde,
      resulting in a heterogeneous population of conjugates rK346- HRPc with molecular
      weights between 150.5 +/- 22.6 to 80.0 +/- 12.0 kDa; with rK346-HRPC
      stoichiometries of 2:1; 1:2; 2:2; and 1:3, with an increased conjugation
      efficiency in compari- son with glutaraldehyde. This enables sulfo-SMCC to be
      used as a potential reagent for cou- pling the antigen to the HRPc, to design an
      economic, specific and easy method to apply as a reporter system, available to
      assess individuals at risk and/or at early and late stages of visceral
      leishmaniasis.

PMID- 28429897
TI  - Single nucleotide polymorphisms V4 and T1 of the ADAM33 gene in Venezuelan
      patients with asthma or chronic obstructive pulmonary disease.
AB  - ADAM33 is a metalloproteinase important in the extracellular matrix for tissue
      remodeling, and, consequently, in asthma and chronic obstructive pulmonary
      disease (COPD). Several polymorphisms of the ADAM33 gene have been associated
      with enzyme activity. One of the most studied polymorphisms is V4, cytosine for
      guanine in the 3 'UTR region, and T1, adenine for guanine in the exon 19 of the
      gen. The aim of this study was to ascertain the possible association among single
      polymorphisms of ADAM33, V4 and T1, in Venezuelan patients with asthma or COPD.
      The polymorphisms V4 and T1 were analyzed in 303 individuals (103 asth- matic,
      100 COPD and 100 controls) by PCR-RFLP (polymerase chain reaction and restriction
      fragment length polymorphisms). There was a significant difference (P<0.05) in
      the frequency of ADAM33 V4 polymorphism in both, asthmatic and COPD patients
      groups, as compared to controls. No significant differences (P=0.4) were found
      for T1 polymorphism. However, there were significant differences (P<O.05) when
      haplotypes and diplotypes of ADAM33 V4/T1 were compared in all three groups. It
      can be concluded that the polymorphism V4 of ADAM33 is associated with asthma or
      COPD in Venezuelan patients.

PMID- 28429898
TI  - Subclassification of the molecular types of breast cancer based on the expression
      of immunohistochemical markers and evolution.
AB  - Breast carcinomas have been classified from the molecular point of view into four
      major groups (Luminal A, Luminal B, HER2 and triple negative). However, these
      groups are not homogeneous and there is a need to establish subcategories that
      can be identified by immunohistochemistry (IHC), to better predict prognosis and
      carry out treatments that are more effective. This study was conducted in 354
      patients diagnosed with invasive ductal breast carci- noma. The expression of 22
      molecules was analyzed by tissue matrices and the results obtained were compared
      with molecular classes defined by IHC, according to the expression of estrogen
      receptor (ER), progesterone receptor (PR) and HER2, and the overall survival. The
      Luminal A molecular class can set various prognosticosubgroups: the subgroup with
      exclusive expression of ER and PR, with Ki-67 <=14%, with a better prognosis, and
      the subgroup of Luminal A with Ki-67> 14% or other expression related to the
      basal phenotype markers. Luminal B group can be divided into subtypes according
      to the expression of Ki-67 (cutoff at 25%). In the HER2 class it seems important
      the Ki-67 index for forecasting (cutoff at 25%). The TN class can be divided
      according to the rate of proliferation into two prognostic categories, with a
      better prog- nosis for tumors with Ki-67 index <=25%.

PMID- 28429899
TI  - Neurotransmitter systems, neuroanatomical pathology and cell death in
      schizophrenia: update and perspectives.
AB  - Schizophrenia is a thought disorder characterized by delusional thinking which
      may be accompanied by hallucinations involving any sensory modality.
      Schizophrenia may be associated with several neurologic and psychiatric
      disorders. Also, it may be induced by drugs. In spite of the similarity in
      psychoses symptomatology, it is unknown if it involves the same underlying
      neurobiologic mechanisms in those cases. Schizophrenic patients exhibit not only
      neuroanatomical alterations, but also, distortion of several neurotransmitter
      systems. Nowadays, the main theories in this regard involve dopaminergic
      hyperfunction and glutama- tergic hypofunction. Additionally, other systems
      involved in the schizophrenia pathophysiology are the nitric oxide pathway as
      well as GABAergic, glycinergic and serotonergic systems. Fur- thermore, those
      systems interact with each other to modulate nervous system development and cell
      survival. The alterations described in this paper may be part of a single cascade
      of events. Research in this field should focus on the elucidation of this chain
      to find its limits, the initial stage that originates it, and the final stage
      that has therapeutic implications.

PMID- 28429900
TI  - Theanine: the unique amino acid in the tea plant as an oral hepatoprotective
      agent.
AB  - For thousands of years, humans have consumed tea made from leaves of Camellia
      sinensis, first as a medicinal herb and then as a widely popular beverage. In the
      past 10 years, theanine, a tea-derived, unique, nonproteinic amino acid, has been
      extensively studied for its health benefits. Recently, multiple lines of evidence
      have proven its beneficial effects on hepatic and immune functions. One possible
      mechanism for its biological activity involves the downregulation of the
      inflammatory response through the induction of nitric oxide production and
      glutathione synthesis. In this review, we summarize published results describing
      the potential mechanisms for these beneficial health effects and provide new
      insight into how theanine can be therapeutic for liver injury and chronic liver
      disease.

PMID- 28429901
TI  - Development of the revised Japanese Maternal Breastfeeding Evaluation Scale,
      short version.
AB  - BACKGROUND AND OBJECTIVES: The Japanese Maternal Breastfeeding Evaluation Scale
      (JMBFES) was developed in 2013 based on the original Maternal Breastfeeding
      Evaluation Scale (MBFES). Mothers' abilities to incorporate breastfeeding into
      their daily life may influence their decision to continue or discontinue to
      breastfeed, but that version of the JMBFES had no questions to measure this
      important aspect of breastfeeding. Therefore, we sought to improve the JMBFES by
      incorporating questions measuring "lifestyle compatibility-incompatibility," and
      we conducted psychometric testing of the improved version. METHODS AND STUDY
      DESIGN: In this longitudinal study, the revised JMBFES was developed, and its
      reliability and validity was tested among 215 Japanese mothers. In the first
      survey, which was done three months after delivery, infant-feeding status and the
      prenatal intention regarding breastfeeding were measured. In the second survey,
      which was done two months later, the JMBFES questions were asked along with
      questions regarding infant-feeding status. We identified items that could be
      deleted while maintaining high reliability. Using regression models, we examined
      associations of JMBFES scores with breastfeeding intention and breastfeeding
      outcomes. RESULTS: All three subscales in the revised JMBFES had acceptable
      reliability (alpha >=0.78). The two "lifestyle compatibility-incompatibility"
      items (one new item and the one that had been deleted previously) belonged to the
      "potentially negative aspects" subscale. Scores on that subscale were not
      associated with breastfeeding intention. However, in both surveys, the mothers
      who were using formula reported more potential difficulties (p<=0.01).
      CONCLUSION: Results of validation testing and reliability testing indicate that
      the revised JBFEES can be used to measure breastfeeding satisfaction among
      Japanese mothers.

PMID- 28429902
TI  - Validity and practicability of smartphone-based photographic food records for
      estimating energy and nutrient intake.
AB  - BACKGROUND AND OBJECTIVES: Image-assisted dietary assessment methods are
      frequently used to record individual eating habits. This study tested the
      validity of a smartphone-based photographic food recording approach by comparing
      the results obtained with those of a weighed food record. We also assessed the
      practicality of the method by using it to measure the energy and nutrient intake
      of college students. METHODS AND STUDY DESIGN: The experiment was implemented in
      two phases, each lasting 2 weeks. In the first phase, a labelled menu and a
      photograph database were constructed. The energy and nutrient content of 31
      randomly selected dishes in three different portion sizes were then estimated by
      the photograph-based method and compared with a weighed food record. In the
      second phase, we combined the smartphone-based photographic method with the
      WeChat smartphone application and applied this to 120 randomly selected
      participants to record their energy and nutrient intake. RESULTS: The Pearson
      correlation coefficients for energy, protein, fat, and carbohydrate content
      between the weighed and the photographic food record were 0.997, 0.936, 0.996,
      and 0.999, respectively. Bland-Altman plots showed good agreement between the two
      methods. The estimated protein, fat, and carbohydrate intake by participants was
      in accordance with values in the Chinese Residents' Nutrition and Chronic Disease
      report (2015). Participants expressed satisfaction with the new approach and the
      compliance rate was 97.5%. CONCLUSIONS: The smartphone-based photographic dietary
      assessment method combined with the WeChat instant messaging application was
      effective and practical for use by young people.

PMID- 28429903
TI  - Causes of interruptions in postoperative enteral nutrition in children with
      congenital heart disease.
AB  - BACKGROUND AND OBJECTIVES: Perioperative nutritional support has become a hot
      topic in the clinical management of congenital heart disease (CHD). Postoperative
      enteral nutrition (EN) offers many benefits, such as protection of the intestinal
      mucosa, reduced risk of infection, and low clinical costs. Interruptions in EN
      frequently influence nutritional support and clinical outcomes. We, therefore,
      aimed to determine the causes of interruptions in postoperative EN in CHD
      patients and discuss clinical counter measures. METHODS AND STUDY DESIGN: We
      analyzed the data of 360 CHD patients to determine the causes of interruptions in
      postoperative EN and develop possible clinical strategies to prevent such
      interruptions. RESULTS: Of the 360 patients (aged from 1 month to 6 years), 198
      patients had at least one EN interruption. The total number of interruptions was
      498 (average, 2.52 interruptions/ patient). Non-gastrointestinal factors (airway
      management, fluid overload, invasive procedure, increased intracranial pressure,
      feeding tube block, and clinical deterioration) accounted for 67.8% (338/498) of
      all interruptions and gastrointestinal factors (vomiting, gastrointestinal
      bleeding, diarrhea, constipation, and large gastric residual volume) accounted
      for 32.2% (160/498). The total number of interruptions and the number of
      interruptions due to gastrointestinal factors were significantly higher in
      younger patients (aged from 1-12 months) than in older patients (aged from 1-6
      years). CONCLUSIONS: Non-gastrointestinal factors were the main causes of
      interruptions in postoperative EN in CHD patients. Younger patients had a greater
      number of interruptions as a whole, and more interruptions caused by
      gastrointestinal factors. Gastrointestinal factors can be reduced by tube feeding
      and use of gastrointestinal motility drugs.

PMID- 28429904
TI  - Effect of lutein supplementation on visual function in nonproliferative diabetic
      retinopathy.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether
      supplementation with lutein improved visual function in patients with
      nonproliferative diabetic retinopathy (NPDR). METHODS AND STUDY DESIGN: In this
      randomized, double-blind, placebo-controlled trial, 31 patients with NPDR were
      assigned randomly to 10 mg/d of lutein or identical placebo for 36 weeks. Visual
      performance indices, including visual acuity (VA), contrast sensitivity (CS) and
      glare sensitivity (GS) at four different spatial frequencies, were measured at
      baseline, week 18 and 36. RESULTS: At 36 weeks, a slight improvement in VA was
      found in the lutein group. A significant association was observed between the
      changes in VA and the corresponding baseline values in treatment group (r=-0.53;
      p=0.04). At 36 weeks, the lutein treatment group increased CS at four spatial
      frequencies, and the improvement achieved statistical significance at 3
      cycles/degree (p=0.02). The changes in CS at 3 cycles/degree for the lutein group
      was marginally significantly greater than those for the placebo group (p=0.09).
      There was also a slight increase in GS in the lutein group up to week 36,
      however, no significant changes were found over time in any cycles/degree.
      CONCLUSIONS: In patients with NPDR, supplementation with lutein resulted in
      potential improvements in CS at low spatial frequency. Further studies are
      required to determine the possibility that such intervention could be used as an
      adjunct therapy to prevent vision loss in diabetic patients.

PMID- 28429905
TI  - Maintenance vitamin D3 dosage requirements in Chinese women with post menopausal
      osteoporosis living in the tropics.
AB  - BACKGROUND AND OBJECTIVES: Vitamin D3 (cholecalciferol) dose required to maintain
      sufficiency in non- Caucasian women with postmenopausal osteoporosis (PMO) inthe
      tropics has not been well studied. Some guidelines mandate 800-1000 IU vitamin
      D/day but the Endocrine Society (US) advocates 1500-2000 IU/day to maintain 25
      hydroxyvitamin-D (25(OH)D) concentration at >75 nmol/L. We aimed to establish
      oral cholecalciferol dose required to maintain 25(OH)D concentration at >75
      nmol/L in PMO Chinese Malaysian women, postulating lower dose requirements
      amongst light-skinned subjects in the tropics. METHODS AND STUDY DESIGN: 90
      Chinese Malaysian PMO women in Kuala Lumpur, Malaysia (2 degrees 30'N) with
      baseline serum 25(OH)D levels >=50 nmol/L were recruited. Prior vitamin D
      supplements were discontinued and subjects randomized to oral cholecalciferol
      25,000 IU/4-weekly (Group-A) or 50,000 IU/4-weekly (Group- B) for 16 weeks,
      administered under direct observation. Serum 25(OH)D, PTH, serum/urinary calcium
      were measured at baseline, 8 and 16 weeks. RESULTS: Baseline characteristics,
      including osteoporosis severity, sun exposure (~3 hours/week), and serum 25(OH)D
      did not differ between treatment arms. After 16 weeks, 91% of women sufficient at
      baseline, remained sufficient on 25,000 IU/4-weekly compared with 97% on 50,000
      IU/4-weekly with mean serum 25(OH)D 108.1+/-20.4 and 114.7+/-18.4 SD nmol/L
      respectively (p=0.273). At trial's end, 39% and 80% of insufficient women at
      baseline attained sufficiency in Group A and Group B (p=0.057). Neither dose was
      associated with hyperparathyroidism or toxicity. CONCLUSIONS: Despite pretrial
      vitamin D supplementation and adequate sun exposure, 25.6% Chinese Malaysian PMO
      women were vitamin D insufficient indicating sunshine alone cannot ensure
      sufficiency in the tropics. Both ~900 IU/day and ~1800 IU/day cholecalciferol can
      safely maintain vitamin D sufficiency in >90% of Chinese Malaysian PMO women.
      Higher doses are required with baseline concentration <75 nmol/L.

PMID- 28429906
TI  - Eating glutinous brown rice for one day improves glycemic control in Japanese
      patients with type 2 diabetes assessed by continuous glucose monitoring.
AB  - BACKGROUND AND OBJECTIVES: We investigated whether intake of non-glutinous brown
      rice (BR) or glutinous brown rice (GBR) for 1 day had an influence on the daily
      glucose profile measured by continuous glucose monitoring (CGM) when compared
      with intake of non-glutinous white rice (WR). METHODS AND STUDY DESIGN: A total
      of 37 inpatients with type 2 diabetes mellitus (T2DM) were recruited for a 3-day
      randomized triple cross-over trial in which they ate WR, BR, or GBR for 1 day
      each. One of the three types of rice was eaten at breakfast, lunch, and dinner on
      the first day, before switching to the other types on the second and third days.
      Each meal had the same energy content and the same side dishes. The main outcome
      measures were the blood glucose profile determined by continuous glucose
      monitoring (CGM) and the profile of serum C-peptide (CPR) for 3 hours after
      breakfast. A self-administered questionnaire was used to assess the palatability
      of each type of rice. RESULTS: According to the CGM data, the mean 24-hour
      glucose concentration was lowest with GBR (p<0.01). Serum Cpeptide showed no
      significant differences among the three diets. Regarding palatability, BR was
      assigned significantly lower scores than WR and GBR (p<0.05), while there was no
      difference between WR and GBR. CONCLUSIONS: GBR intake suppressed the whole-day
      glucose profile of patients with T2DM, mainly by reducing postprandial glucose
      excursion, and GBR was preferred over BR with respect to palatability. GBR may be
      worth adding to the diet of patients with T2DM.

PMID- 28429907
TI  - Seasonal vitamin D and bone metabolism in women of reproductive age in urban
      Beijing.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to evaluate the relationship between
      serum 25-hydroxy-vitamin D and bone metabolism in healthy women of reproductive
      age. METHODS AND STUDY DESIGN: This study included 100 healthy female residents
      of Beijing (23-30 years old), who underwent bone ultrasonography as well as
      testing to evaluate serum25-hydroxy-vitamin D, parathyroid hormone, bone alkaline
      phosphatase, calcium, sodium, phosphorus, and alkaline phosphatase. RESULTS: Mean
      25-hydroxy-vitamin D in the winter (22.3+/-3.55 nmol/L) was significantly lower
      than that in the summer (46.2+/-16.3 nmol/L). In the winter, a negative
      correlation was observed between 25-hydroxy-vitamin D and parathyroid
      hormone(r=0.300, p=0.002) and bone alkaline phosphatase (r=0.274, p=0.016). In
      the summer, a negative correlation was observed between 25-hydroxy-vitamin D and
      parathyroid hormone (r=0.386, p<0.001) and bone alkaline phosphatase (r=0.523,
      p<0.001). Serum calcium, sodium, phosphorus, and alkaline phosphatase were within
      the normal ranges for both winter and summer, and exhibited no significant
      correlations with serum 25-hydroxy-vitamin D. The mean speed of sound during bone
      ultrasonography was 4,125+/-365 m/s, and a linear correlation was observed
      between 25-hydroxy-vitamin D and the speed of sound (r=0.215, p=0.031). Serum
      alkaline phosphatise was not correlated with bone alkaline phosphatase.
      CONCLUSION: Serum vitamin D deficiency was common among healthy women of
      childbearing age in Beijing during both winter and summer. Furthermore, bone
      ultrasonography findings and serum vitamin D, parathyroid hormone, and bone
      alkaline phosphatase accurately reflected these women's bone metabolism status.

PMID- 28429908
TI  - Pre-pregnancy body mass index as a predictor of low birth weight infants in
      Japan.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of low birth weight (LBW) infants in
      Japan has doubled in the last several decades. The objective of this study was to
      examine the effects of pre-pregnancy body mass index (BMI) and gestational weight
      gain (GWG) on LBW infants of Japanese women. METHODS AND STUDY DESIGN: This
      retrospective study was conducted using data on 1,336 mothers (mean age, 34.0
      years)whose pre-pregnancy BMI was less than 23 kg/m2 and their singleton infants
      were born at full term between January and December in 2011. The outcome of
      interest was LBW infants (less than 2,500 g). The main exposure variables were
      pre-pregnancy BMI and GWG. The effects of these two variables on LBW were
      determined after adjusting for confounder variables such as maternal age,
      smoking, drinking, parity, gestational week at birth and infant gender. RESULTS:
      The proportion of LBW infants was 4.2% in total, 6.1% among underweight mothers
      (<18.5 kg/m2) and 3.5% among normal weight mothers (18.5-22.9 kg/m2).A stepwise
      multivariable logistic regression model showed that underweight mother were more
      likely [odds ratio (OR) 1.86, 95% confidence interval (CI), 1.04-3.31] than
      normal weight mother to deliver a LBW infant. Mothers with inadequate GWG <8.5 kg
      were more likely to deliver a LBW infant (OR 1.66, 95% CI: 0.80-3.45) compared
      with mothers who gained 10.5-12.4 kg (the third lowest quartile) but this did not
      reach statistical significance. CONCLUSIONS: This study demonstrated that mothers
      who were underweight before pregnancy were independently associated with the
      delivery of LBW infants.

PMID- 28429910
TI  - Dietary patterns and their associations with energy, nutrient intake and
      socioeconomic factors in rural lactating mothers in Tibet.
AB  - BACKGROUND AND OBJECTIVES: There is very limited published data on Tibetan
      dietary patterns and its association with nutrient intakes and socioeconomic
      factors. The aim of this study was to identify and describe the dietary patterns
      and the associations with nutrient intakes in rural Tibetan pregnant, lactating
      mothers. METHODS AND STUDY DESIGN: Dietary patterns and nutrient intakes were
      identified via a food frequency questionnaire (FFQ). We identified dietary
      patterns using principle component analysis (PCA) of intakes of 17 food groups
      and specific Tibetan foods. Quartile categories of each dietary pattern were
      used, and non-dietary lifestyle factors and total energy intake were adjusted for
      the analysis. We identified two dietary patterns: "Varied pattern" and "Staple
      pattern". RESULT: The "Varied pattern" was characterized by a high intake of
      vegetables, fruits and soy foods which showed significant positive associations
      with vitamins. Vitamin C (Ptrend<0.01) and vitamin E (Ptrend<0.01) were strongly
      associated with "Varied pattern" among mothers with children younger or older
      than 12 months. The "Staple pattern" was characterized by Tibetan staple foods,
      Tibetan beverages and Tibetan snacks and showed significant negative associations
      with protein (Ptrend<0.01) among mothers with children younger than 12 months or
      older than 12 months. Carbohydrate intakes significantly increased with "Staple
      pattern" among mother with children younger than 12 months only. CONCLUSIONS: The
      results presented here suggested our dietary patterns to great extent
      characterize the dietary behavior of Tibetan lactating mothers. There is,
      therefore, potential for dietary patterns to be used as a valid tool in assessing
      Tibetan diet.

PMID- 28429909
TI  - Association between maternal vitamin D status during pregnancy and offspring
      cognitive function during childhood and adolescence.
AB  - BACKGROUND AND OBJECTIVES: Animal studies have demonstrated poor cognitive
      outcomes in offspring in relation to maternal vitamin D deficiency before and/or
      during pregnancy. Human studies linking maternal vitamin D status during
      pregnancy with offspring cognitive function are limited. We aimed to test the
      hypothesis that lower maternal vitamin D status during pregnancy is associated
      with poor offspring cognitive ability in an Indian population. METHODS AND STUDY
      DESIGN: Cognitive function was assessed in children from the Mysore Parthenon
      birth cohort during childhood (age 9-10 years; n=468) and adolescence (age 13-14
      years; n=472) using 3 core tests from the Kaufman Assessment Battery for children
      and additional tests measuring learning, long-term retrieval/ storage, short-term
      memory, reasoning, verbal fluency, visuo-spatial ability, and attention and
      concentration. Maternal serum 25-hydroxyvitamin D concentration was measured at
      30+/-2 weeks of gestation. RESULTS: During pregnancy 320 (68%) women had 'vitamin
      D deficiency' (serum 25-hydroxyvitamin D concentration <50 nmol/L). Girls scored
      better than boys in tests of short-term memory, reasoning, verbal fluency, and
      attention (p<0.05 for all). Maternal vitamin D status (low as well as across the
      entire range) was unrelated to offspring cognitive function at both ages, either
      unadjusted or after adjustment for the child's current age, sex, maternal age,
      parity, season at the time of blood sampling, gestational age, the child's birth
      and current size, socio-economic status, parents' education, maternal
      intelligence and home environment. CONCLUSIONS: In this population, despite a
      high prevalence of vitamin D deficiency during pregnancy, there was no evidence
      of an association between maternal vitamin D status and offspring cognitive
      function.

PMID- 28429911
TI  - Inequality in malnutrition by maternal education levels in early childhood: the
      Prospective Cohort of Thai Children (PCTC).
AB  - BACKGROUND AND OBJECTIVES: As tackling socioeconomic inequality in child
      malnutrition still remains one of the greatest challenges in developing
      countries, we examined maternal educational differences in malnutrition and the
      magnitude of its inequality among 4,198 children from the Prospective Cohort
      study of Thai Children (PCTC). METHODS AND STUDY DESIGN: Prevalence of stunting,
      underweight, and wasting from birth to 24 months was calculated using the new WHO
      growth chart. The Relative Index of Inequality (RII) was used to examine the
      magnitude and trend of inequality in malnutrition between maternal educational
      levels. RESULTS: The low education group had lower weight and height in most ages
      than the high education group. Faltering in height was observed in all education
      levels, but was most remarkable in the low education group. On the other hand,
      while upward trends for weight-for-age and weight-for-height across ages were
      observed in the high education group, a marked decline between 6 to 12 months was
      observed in the low education group. An increasing trend in inequality in The RII
      revealed an increasing trend in inequality in stunting, underweight, and wasting
      by maternal education levels was observed during infancy with an almost monotonic
      increase until 24 months, although the inequality in wasting decreased after 18
      months of age. CONCLUSION: Inequality in malnutrition remarkably increased during
      infancy, and for stunting and underweight it remained until 24 months. These
      findings shed light on the extent of malnutrition inequality during the first 2
      years of life and they suggest sustainable efforts must be established at the
      national level to tackle the malnutrition inequality in infancy.

PMID- 28429912
TI  - Growth patterns during the first 12 months of life: post-hoc analysis for South
      Australian Aboriginal and Caucasian infants in a randomised controlled trial of
      formula feeding.
AB  - BACKGROUND AND OBJECTIVES: To compare growth characteristics of Aboriginal and
      Caucasian formula-fed in-fants in the first 12 months of life. METHODS AND STUDY
      DESIGN: We conducted post-hoc data analysis of infants who were part of a
      previous randomised controlled trial comparing infants randomly assigned to cow
      or goat milk-based infant formulae. Weight, height, and body composition were
      assessed at serial time points between study entry (~1-2 weeks of age) and 12
      months. There was no growth difference between the randomised groups so the two
      groups were combined and the data were used to conduct a non-randomised
      comparison of the growth between Aboriginal (n=11) and Caucasian formula-fed
      (n=169) infants. RESULTS: Aboriginal formula-fed infants had significantly higher
      mean z-scores for weight (0.65 difference, [95% CI 0.11, 1.18], p=0.018) and
      weight-for-length (0.82 difference [95% CI 0.20, 1.44], p=0.010) at 2 months, and
      all time points onward compared with Caucasian formula-fed infants. Mean length z
      scores and the overall growth trajectory across time did not differ between
      Aboriginal and Caucasian formula-fed infants. Concordant with the weight and
      weight-for-length z-scores, Aboriginal infants had increased fat mass at 2 months
      (292 g difference [95% CI 56, 528], p=0.015), and all time points onward compared
      to Caucasian infants. There was no difference in fat free mass. CONCLUSIONS:
      Though there was only a small number of Aboriginal infants for comparison, our
      data indicate Aboriginal formu-la-fed infants were heavier and had a larger
      increase in fat mass over time compared with Caucasian formula-fed infants.
      Further studies using a larger cohort are needed to substantiate these findings.

PMID- 28429913
TI  - Effect of glucomannan on functional constipation in children: a systematic review
      and meta-analysis of randomised controlled trials.
AB  - BACKGROUND AND OBJECTIVES: Constipation, a common complaint in children,
      considerably affects the quality of life. This systematic review assessed the
      treatment effects of glucomannan on children with constipation by summarising
      evidence from previous randomised controlled trials (RCTs). METHODS AND STUDY
      DESIGN: A comprehensive electronic literature search was conducted for
      identifying eligible RCTs that evaluated the effectiveness of glucomannan. The
      results were reported as mean differences (MDs), standardised mean differences
      (SMDs), and risk ratios (RRs) with 95% confidence intervals (CIs). The primary
      outcome was the defecation frequency per week; the secondary outcomes were stool
      consistency and the rate of successful treatment. A metaanalysis was conducted
      using the random effects model. RESULTS: Three RCTs evaluating 122 participants
      were identified. Glucomannan use was associated with an increased frequency of
      defecation (3 trials; MD=1.40; 95% CI: 0.36-2.44, p=0.008); however, there were
      no significant differences in the outcomes of stool consistency (3 trials;
      SMD=0.48; 95% CI: -0.44 to 1.40, p=0.300) or the rate of successful treatment (2
      trials; RR=1.36; 95% CI: 0.48-3.81, p=0.110). CONCLUSIONS: Glucomannan moderately
      increases the defecation frequency of children with constipation but is not
      associated with a reduction in stool consistency or overall improvement in the
      rate of successful treatment. However, these results should be cautiously
      interpreted because of the small sample size and the risk of products containing
      glucomannan need to be considered. Additional large-scale and well-designed RCTs
      are necessary to evaluate the efficacy and long-term safety of glucomannan.

PMID- 28429914
TI  - The presence and accuracy of nutritional labelling of pre-packaged foods in
      Shanghai.
AB  - BACKGROUND AND OBJECTIVES: The Chinese government officially enacted the
      Regulation on the Management of Food Nutrition Labelling in 2007 and the General
      Rules for Nutrition Labelling of Pre-packaged Foods in 2011. Our investigation
      examined the presence and accuracy of nutrition labelling of pre-packaged foods
      in Shanghai and provides baseline data for future studies. METHODS AND STUDY
      DESIGN: Nutrition labels on pre-packaged foods were recorded by photograph,
      transcription, or purchase in four supermarkets in Shanghai. We compared the
      observed labelling rate with results from a survey conducted in 2008. To assess
      labelling accuracy, we sent randomly selected foods to an analytical laboratory
      to test food energy and nutrient content. RESULTS: The overall labelling rate was
      54.8%, representing a great improvement over the rate measured prior to
      implementation of the Regulation (35.4%). The labelling rate for energy content
      and core nutrients were all above 98%, whereas the rates for saturated fat, trans
      fatty acids, and iron were 11.5%, 7.0%, and 10.7%, respectively. Pre-packaged
      foods manufactured by domestic Chinese companies were labelled less frequently
      (45.8%) than foods manufactured by companies from Taiwan/Hong Kong (67.0%) or
      overseas (65.7%). The accuracy of carbohydrate content on labels was as high as
      100%, while the accuracy of protein and fat content were 94.4% and 96.0%,
      respectively. CONCLUSION: Pre-packaged food manufacturers and government agencies
      should collaborate to improve the management of nutrition labelling. Mandatory
      regulations may be the best way to ensure that nutrition labelling facilitates
      informed consumer decision-making.

PMID- 28429915
TI  - Adolescent women as a key target population for community nutrition education
      programs in Indonesia.
AB  - BACKGROUND AND OBJECTIVES: Adolescence is a critical life-stage that sets the
      foundation for health in adulthood. Adolescent women are a unique population and
      should be targeted as such for nutrition promotion activities. Using Indonesia as
      a case study, this qualitative study aimed to identify existing nutrition
      promotion programs aimed at adolescent girls, how best to target this population
      and effective recommendations to inform nutrition education program design for
      this important group. METHODS AND STUDY DESIGN: Semi-structured interviews and
      questionnaires were conducted with ten key informants working in public health in
      Indonesia. Interview transcripts were analysed and coded to identify key themes.
      RESULTS: No existing nutrition education programs targeting adolescent women in
      Indonesia were identified. Several strategies apply to nutrition programs for
      adolescent girls: 1) nutrition promotion messages that are relevant to the
      lifestyles and interests of adolescent women; 2) technology-based interventions
      show promise, however, they need to be appropriately targeted to sub-groups; 3)
      school remains an important setting; and 4) early marriage is an important issue
      affecting nutritional status and engagement of adolescent girls. The informants
      recommended that: 1) more research is needed about the underlying motivations for
      behaviour change among adolescent women and ways to effectively implement the
      identified engagement strategies; 2) adolescent girls should be included in
      program design to improve its suitability and uptake; and 3) government budget
      and policy support is crucial to success. CONCLUSIONS: Adolescent women are an
      important population group and more research is required to identify the optimal
      forms of engagement to improve nutrition programs for them.

PMID- 28429916
TI  - Opportunities and barriers to public health nutrition education in Vietnamese
      universities.
AB  - BACKGROUND AND OBJECTIVES: A core challenge for low- and middle-income countries
      (LMICs) in combating the negative effects of the nutrition transition is to
      implement appropriate prevention strategies to halt the increasing prevalence of
      obesity and non-communicable diseases (NCDs), against a background of prevailing
      under nutrition. There have been several proposals for the enhancement of
      university nutrition education for future health and related professionals who
      are expected to communicate knowledge of health risks to the broad community.
      However, little is known about university nutrition education in LMICs. The
      present study aimed to investigate professional development opportunities and
      barriers for university nutrition lecturers to teach public health nutrition
      (PHN). METHODS AND STUDY DESIGN: An online survey was conducted among 242
      Vietnamese health and education professionals and university nutrition lecturers
      across Vietnam. Purposive sampling was used to recruit participants. Comparisons
      of between the groups' responses were examined via SPSS Crosstabs. The structures
      of the perceived barriers and desired PHN training topics were examined via
      factor analyses. Multiple linear regression examined the influences on lecturers'
      learning interests in nutrition areas. RESULTS: The lecturers' learning interests
      spanned four areas: basic nutrition, basic food, food policy and 'new' trends
      (e.g. food policy, marketing). Major impediments to nutrition teaching in
      universities divided into two groups: resource limitations and professional
      constraints (e.g. lack of relevant training opportunities). The lecturers'
      perceptions of professional constraints influenced their interest in learning
      about 'new' trends. CONCLUSIONS: The results highlighted the need and
      opportunities to enhance PHN professional development for nutrition lecturers in
      Vietnam.

PMID- 28429917
TI  - The impact of urbanization on the community food environment in China.
AB  - BACKGROUND AND OBJECTIVES: Research on how urbanization has influenced the food
      environment in China is limited. The study aimed to examine the impact of
      urbanization on the food environment in China. METHODS AND STUDY DESIGN:
      Longitudinal data collected during 1989-2009 from the China Health and Nutrition
      Survey were used, which covered 9 provinces in China. Urbanicity index (0-10) was
      assessed using an urbanicity scale. Final analyses included 216 communities.
      Random-effect models were used in analyses. RESULTS: Urbanization (higher
      urbanicity index) increased the odds of having fast food restaurants (OR=2.78,
      95% CI: 2.18-3.54) and other indoor restaurants (OR=2.93, 95% CI: 2.28-3.76)
      within the community, the odds of having supermarkets (OR=2.43, 95% CI: 2.04
      2.89) and free markets (OR=2.56, 95% CI: 1.77-3.70) within 30 minutes' bus ride
      from the community. Food prices for apples (beta=0.06, 95% CI: 0.04-0.08) and
      lean pork (beta =0.02, 95% CI: 0.01-0.03) increased with urbanicity, while prices
      for other food did not. Urbanicity was positively associated with community norms
      for fast food consumption (RR=1.28, 95% CI: 1.22-1.33), fast food preferences
      (RR=1.09, 95% CI: 1.06-1.12) and nutrition knowledge (RR=1.02, 95% CI: 1.01
      1.03). CONCLUSIONS: Urbanization is associated with food environment in China.
      The findings provide insight for future economic development and public health
      efforts related to urbanization.

PMID- 28429919
TI  - Home availability of fruit and vegetables and obesogenic foods as an indicator of
      nutrient intake in 50 year olds from Canterbury, New Zealand.
AB  - BACKGROUND AND OBJECTIVES: The home food environment is known to influence
      children's diet and selected health outcomes. However, similar research in adults
      is scarce. The home is arguably the most important food environment for New
      Zealand adults as the majority of food consumed is stored and prepared in the
      home. Therefore we investigated relationships between home food availability and
      nutrient intake in 50 year olds from Canterbury, New Zealand. METHODS AND STUDY
      DESIGN: A cross-sectional study where participants completed a home food
      inventory and a four-day estimated food diary. Regression analysis was used to
      investigate relationships between home availability of 'Fruit and Vegetables' and
      'Obesogenic Foods' and intake of selected nutrients, adjusting for Body Mass
      Index and demographic factors. Men and women (n=216) aged 50 were randomly
      selected from Canterbury District Health Board area electoral rolls. RESULTS:
      Women with a high 'Obesogenic Foods' score were significantly more likely to have
      a high intake of saturated fat (OR 5.8, CI: 1.67, 19.6) and high sugar intake (OR
      3.1, CI: 1.23, 7.58). Men with a high 'Obesogenic Foods' score were less likely
      to have high folate (OR 0.14, CI: 0.05, 0.40) and fibre intake (OR 0.21, CI:
      0.07, 0.60). Men and women with a higher 'Fruit and Vegetables' score were more
      likely to have high vitamin C intake (OR 5.6 and 4.5 respectively). CONCLUSIONS:
      Home Food Inventory scores are associated with selected nutrient intakes,
      particularly in women, suggesting that they are useful for identifying those
      groups with less favourable nutrient intakes. Future research should investigate
      whether these scores can predict health outcomes.

PMID- 28429918
TI  - Relationship between fruit and vegetable intake and the risk of metabolic
      syndrome and its disorders in Korean women according to menopausal status.
AB  - BACKGROUND AND OBJECTIVES: The association between fruit and vegetable (FV)
      intake and risk of the metabolic syndrome (MetS) has not been elucidated fully,
      particularly by menopausal status. Method and Study Design: The study population
      was 2,999 women aged 40-64 years participating in the 4th Korea National Health
      and Nutrition Examination Survey. The definition of MetS and its components was
      based on the modified National Cholesterol Education Program Adult Treatment
      Panel III (NCEP ATP III) for Koreans. Dietary data were assessed by a 24-hour
      recall. RESULTS: Fruit intake was inversely related only to the risk of high
      blood pressure (BP), but not MetS. Total vegetable consumption was inversely
      associated with the MetS risk, and when combined with fruits, the inverse
      association was observed even in its features of high triglycerides (TG) and low
      HDLcholesterol as well as MetS. Assessing women by menopausal status revealed
      that the inverse association with the MetS risk was found only in postmenopausal
      women having greater total vegetables and total FV intake (aOR=0.47, 95% CI=0.29
      0.75, p-trend=0.003 and aOR=0.54, 95% CI=0.35-0.85, p-trend=0.007, respectively).
      Analysis regarding MetS features showed that while the inverse association of
      total vegetables or total FV intake was observed with high TG risk in
      postmenopausal women, fruits intake was inversely associated with high BP risk in
      premenopausal women (aOR=0.54, 95% CI=0.37-0.79, p-trend=0.004). CONCLUSION:
      Results suggest that while fruit intake was inversely associated with high BP in
      premenopausal women, greater dietary intake of vegetables and total FV may
      protect against the risk of MetS, particularly in postmenopausal women.

PMID- 28429920
TI  - The association of dietary patterns and the incidence of insulin resistance after
      a 3-year follow-up: Tehran Lipid and Glucose Study.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the
      relationship between major dietary patterns and the risk of insulin resistance
      (IR) among an urban Iranian population. METHODS AND STUDY DESIGN: In this
      longitudinal study, 802 adult men and women were studied within the framework of
      Tehran Lipid and Glucose Study. Fasting serum insulin and glucose were measured
      at baseline and again after a 3-year of followup. The usual dietary intakes were
      assessed using a validated 168 item semi-quantitative food frequency
      questionnaire and major dietary patterns were obtained using principal component
      analysis. Logistic regression models were used to estimate the occurrence of IR
      across tertiles of dietary patterns with adjustment for potential confounding
      variables. RESULTS: Mean age of participants was 39.0+/-11.2 years and 45.5% were
      men. Three major dietary patterns including the Western, traditional and healthy
      were extracted, which explained 25.3% of total variance in food intake. The
      healthy dietary pattern, loaded heavily on intake of vegetable oils, fresh and
      dried fruits, low-fat dairy, nuts and seeds, was accompanied with a reduced risk
      of insulin resistance by 51% (OR=0.49, 95% CI=0.30-0.81), and 81% (OR=0.19, 95%
      CI=0.10-0.36), in the second and third tertile, respectively (p trend=0.001). In
      the presence of all dietary pattern scores in the logistic regression model, a
      45% reduced risk of IR was observed per 1 unit increase in healthy dietary
      pattern score. CONCLUSION: These findings confirmed the protective effect of a
      plant-based, low-fat dietary pattern against the development of insulin
      resistance as a main risk factor of type 2 diabetes and metabolic disorders.

PMID- 28429921
TI  - Relationship between dietary patterns and brachial-ankle pulse wave velocity
      among middle-aged adults in Japan.
AB  - BACKGROUND AND OBJECTIVES: Arterial stiffness is a leading cause of
      cardiovascular disease (CVD), and it is considered to be affected by dietary
      intake. However, few studies have examined the relationship between major dietary
      patterns and brachial-ankle pulse wave velocity (baPWV) among Japanese middle
      aged subjects. We studied whether major dietary patterns were associated with
      baPWV in this population. METHODS AND STUDY DESIGN: Between 2009 and 2012, 70
      Japanese middle-aged subjects (39 men and 31 women) with no history of stroke,
      coronary heart disease, or cancer were studied. Dietary intake was documented
      using a validated food-frequency questionnaire, and dietary patterns were
      generated using factor analysis. Correlational analyses were performed between
      baPWV and identified dietary patterns and between baPWV and individual risk
      factors (total cholesterol, triglyceride, low-density lipoprotein cholesterol
      [LDL-C], high-density lipoprotein cholesterol [HDL-C], non- HDL-C, LDL/HDL ratio,
      and augmentation index). RESULTS: Two dietary patterns were identified: a rice
      rich pattern (high in rice, breads, oils and fats, meats, and confectionery) and
      a vegetable-rich pattern (high in vegetables, fruit, fish, and seaweed). The rice
      rich pattern was not associated with baPWVor other risk factors. A significant
      inverse correlation was found between baPWV and the vegetable-rich dietary
      pattern (p<0.05). CONCLUSIONS: Our findings suggest that a dietary pattern
      characterized by high consumption of vegetables, seafood, seaweed, fruit, and
      pulse is inversely associated with arterial stiffness measured by baPWV. This
      diet offers an additional nutritional approach to the prevention and treatment of
      arterial stiffness.

PMID- 28429922
TI  - Effect modification of green tea on the association between rice intake and the
      risk of diabetes mellitus: a prospective study in Japanese men and women.
AB  - BACKGROUND AND OBJECTIVES: Recent observational studies have suggested a positive
      association of white rice and protective associations of green tea and coffee
      with the risk of diabetes. However, none have examined the interaction between
      these dietary factors on the risk of diabetes. We prospectively investigated the
      effect modification of green tea and coffee on the association between rice and
      incident diabetes in elderly Japanese men and women. METHODS AND STUDY DESIGN:
      Among subjects who participated in the baseline survey (2004-2007), 11717 (91 %)
      subjects responded to the follow-up survey (2010-2012). By using multiple
      logistic regression analysis, ORs of incident diabetes were calculated according
      to categories of cereal food, green tea, and coffee intakes, examining also the
      effect modification of green tea and coffee. RESULTS: 464 new cases of diabetes
      were identified. Women, but not men, showed a positive association of rice intake
      (trend p=0.008) and an inverse association of green tea intake (trend p=0.02)
      with incident diabetes. Coffee showed no association with incident diabetes
      either in men or women. In the analysis stratified by green tea intake, the
      association between rice and diabetes disappeared among women with an intake of
      >=7 cups/d of green tea (interaction p=0.08). CONCLUSIONS: Rice intake was
      associated with an increased risk of diabetes only in women, and women with a
      higher intake of green tea had a lower risk of diabetes. A high intake of green
      tea may be protective against increased risk of diabetes with a higher intake of
      rice in women.

PMID- 28429923
TI  - Combined associations of physical activity and dietary intake with health status
      among survivors of the Great East Japan Earthquake.
AB  - BACKGROUND AND OBJECTIVES: Each of the effects of physical activity and dietary
      intake on health is well known, but combined associations of physical activity
      and dietary intake on health has not been reported yet. Physical activity and
      dietary intake are key factors for maintaining health of survivors of the Great
      East Japan Earthquake in 2011. This study aimed to examine combined associations
      of physical activity and dietary intake with survivors' health status. METHODS
      AND STUDY DESIGN: We used data from 6668 participants of a cross-sectional survey
      taken 3 years (2013) after the disaster. To evaluate combined associations of
      physical activity and dietary intake, answers to questions regarding these two
      variables were categorized into four groups: poor physical activity and poor
      dietary intake (Group 1), poor physical activity and good dietary intake (Group
      2), good physical activity and poor dietary intake (Group 3), and good physical
      activity and good dietary intake (Group 4). Multiple logistic regression analyses
      were performed by sex, with good self-rated health and good mental health as
      dependent variables, and age, place of residence, living conditions and physical
      activity/dietary intake group (with Group 1 as the reference category) as
      independent variables. RESULTS: Good self-rated health was associated with age in
      both sexes, and Groups 3 (male: odds ratios (ORs) 1.84 (95% confidence intervals
      (95% CIs) 1.32-2.57), female: OR 1.82 (95% CI 1.32-2.51)) and 4 (male: OR 1.96
      (95% CI 1.39-2.76), female: OR 1.94 (95% CI 1.42-2.64)). Good mental health was
      associated with Groups 3 (OR 1.48 (95% CI 1.10-1.97)) and 4 (OR 1.86 (95% CI 1.37
      1.97)) for male respondents; and living place (other than temporary housing) (OR
      1.45 (95% CI 1.26-1.68)) was associated with Group 4 (OR 1.42 (95% CI 1.09-1.85))
      for female respondents. CONCLUSIONS: Good physical activity alone or combined
      with good dietary intake was associated with good self-rated health and good
      mental health. Further interventions regarding physical activity and dietary
      intake are needed to improve the health status of survivors.

PMID- 28429924
TI  - Dietary choice and health behaviors in eastern Chinese women: a descriptive,
      population-based survey and review of public health data.
AB  - BACKGROUND AND OBJECTIVES: Urbanization in China has increased the prevalence of
      high-fat and low-fiber diets, and of adverse health behaviors associated with an
      increased risk of diet-related, non-communicable diseases (DR-NCDs) in eastern
      Chinese women. This study aimed to characterize the dietary intake and health
      behaviors in eastern Chinese women. METHODS AND STUDY DESIGN: Retrospective data
      of 122,058 women aged 25 to 70 who completed a multi-staged, stratified, cluster
      sampling epidemiological survey in eastern China in 2008, including self-report
      of diet and lifestyle information (sleep, physical activity, work, etc.). The
      survey included food groups (on a 4-point scale from daily to rarely) and health
      behaviors. RESULTS: Of 122,058 surveyed women, 2008 (1.6%) smoked tobacco, 4326
      (3.5%) consumed alcohol, 10,274 (8.4%) reported insomnia, and 38,305 (31.4%)
      exercised regularly. Consumption was most commonly reported as daily for
      vegetables/fruits (68.1%); 3-4/week for garlic (31.7%); 1-2/week for bean
      products (39.4%), red meat (40.8%), corn (36.6%), and carrots (41.9%); and rarely
      for milk products (46.4%), fried food (42.1%) and charcuterie (55.8%).
      CONCLUSIONS: This study suggests some overall positive lower rates of tobacco
      use, alcohol consumption and insomnia than reported previously, but physical
      exercise was also decreased. Dietary habits were relatively healthy.

PMID- 28429925
TI  - Robot-assisted laparoendoscopic single-site versus mini-laparoscopic pyeloplasty:
      a comparison of perioperative, functional and cosmetic results.
AB  - BACKGROUND: New approaches have been developed to further reduce the invasiveness
      of laparoscopic pyeloplasty (P) as treatment for uretero-pelvic junction
      obstruction (UPJO). Aim of the study was to compare perioperative, functional and
      cosmetic results of mini-laparoscopic (mL-P) versus robot-assisted
      laparoendoscopic single-site P (rLESS-P). METHODS: Since April 2009 to June 2010,
      12 adult patients with primary UPJO, BMI<25 and no previous abdominal surgeries
      were enrolled undergoing mLP (3-mm instruments only). With the same indications
      since February 2012 to October 2013, 15 patients underwent rLESS-P with "single
      site"(r) platform (Intuitive Surgery Inc, Sunnyvale, CA, USA). Success of
      surgeries was determined by clinical parameters and renal scan (success if T
      1/2<20 min) at 12 months postoperatively. Demographics and perioperative results
      were analyzed. Cosmetic results were assessed by using the Patient Scar
      Assessment Questionnaire (PSAQ). RESULTS: Groups were comparable at baseline. No
      differences were found in perioperative variables except for a longer operative
      time in rLESS-P group (128 vs. 190, P<0.001). Postoperative complications rate,
      analgesic consumption, pain visual analogue scale scores, hospital stay and
      success rate of surgeries were not significantly different between the groups.
      PSAQ revealed that in both the groups patients were satisfied with the cosmetic
      result. At one-year follow-up no recurrences were observed. Semiquantitative
      analysis of costs revealed an extra-cost for rLESS-P of ? 3410 per procedure.
      CONCLUSIONS: In our experience, both mLP and rLESS-P appeared to be feasible and
      safe in the treatment of UPJO and allowed for excellent cosmetic results. r-LESS
      required longer operative times and higher costs.

PMID- 28429926
TI  - The efficacy of intraurethral lidocaine in optical internal urethrotomy for
      anterior urethral stricture: a multicenter study.
AB  - BACKGROUND: Male anterior urethral strictures can be treated successfully with
      the help of optical internal urethrotomy (OIU) and is usually performed under
      general or regional anesthesia. In this study, we determined the efficacy of
      intraurethral lidocaine in OIU for anterior urethral stricture in an outpatient
      setting. METHODS: A total 157 patients with anterior urethral strictures
      underwent OIU under local urethral anesthesia with lidocaine. Optical urethrotomy
      was performed with a cold-cutting knife. Visual analogue scale (VAS) was used to
      evaluate patient discomfort and pain levels. RESULTS: Using local anesthesia with
      lidocaine 2%, internal urethrotomy under vision was successfully completed in 151
      of 157 patients. The overall success rate 96.1%. A total of 125 patients
      experienced mild, 26 patients moderate and 6 patients severe pain. The procedure
      was not completed in six patients because of severe pain. These patients went on
      OIU under general anesthesia. 18 (11.4%) recurrent strictures were seen during at
      least 6 months of follow-up. CONCLUSIONS: Topical intraurethral lidocaine is a
      simple and efficacious anesthesia technique for surgical procedures on the
      anterior urethra. It is a safe, cost-effective and a well tolerated procedure.
      OIU under topical anesthesia can be easily performed and satisfactorily completed
      in an outpatient setting. It is anesthetic efficacy and reasonable success rate
      when compared with the other anesthetic techniques may provide an alternative
      approach in the management of urethral strictures.

PMID- 28429927
TI  - Endovascular correction in acute bleeding after femoro-popliteal bypass: a single
      center experience.
AB  - BACKGROUND: The endovascular correction (EC) has emerged in recent years as a
      possible alternative to surgical revision (SR) in case of bleeding complications
      after peripheral bypass (PB). The purpose of this study is to evaluate the
      efficacy and safety of EC compared to SR in case of bleeding complications of PB.
      METHODS: From January 2004 to December 2014, we have submitted 32 patients to
      surgery for acute bleeding in previous PB (25 venous bypass, in situ or reversed,
      6 PTFE bypass and 1 composite bypass). The cause of the bleeding was the
      dehiscence of proximal anastomosis in 14 patients, the dehiscence of distal
      anastomosis in 11 patients and the rupture of the graft in 7 patients. All
      patients postoperatively underwent anticoagulation or antiplatelet therapy,
      antibiotic therapy and close ultrasound follow-up. Patency rate, limb salvage
      rate and survival rate in the short term were assessed by Kaplan-Meier curves.
      RESULTS: Of the 32 patients treated for acute bleeding in previous PB, 11
      underwent endovascular correction with a technical success of 100% (no need for
      reintervention), while in 21 patients a surgical revision was performed. Among
      the latter, in 4 cases (19.1%) an early bleeding occurred, and endovascular
      correction was promptly performed solving the bleeding in the absence of sequelae
      (then a total of 15 patients were treated by endovascular correction). The 12
      month patency, limb salvage and survival rates were respectively 71.4%, 88.2% and
      88.2% in the SR group and 80%, 93.3% and 100% in the EC. CONCLUSIONS: This topic
      underlines that endovascular correction after peripheral bypass bleeding is an
      attractive alternative to surgery, but there are still a few data to change the
      gold standard treatment. Randomized clinical trials comparing the two treatment
      options are warranted.

PMID- 28429928
TI  - A Dual-Enzyme Hydrogen Peroxide Generation Machinery in Hydrogels Supports
      Antimicrobial Wound Treatment.
AB  - The aging population and accompanying diseases like diabetes resulted in an
      increased occurrence of chronic wounds. Topical wound treatment with
      antimicrobial agents to inhibit bacterial invasion and promote wound healing is
      often associated with difficulties. Here, we investigated the potential of
      succinyl chitosan (SC)-carboxymethyl cellulose (CMC) hydrogels which constantly
      release clinically relevant levels of hydrogen peroxide (H2O2). CMC hydrogel
      matrix was in situ converted by limited hydrolysis by a cellulase into substrates
      accepted by cellobiose dehydrogenase (CDH) for continuous production of H2O2 (30
      MUM over 24 h). This dual-enzyme catalyzed in situ H2O2 generation system proved
      its antimicrobial activity in a zone of inhibition (ZOI) assay best simulating
      the application as wound dressing and was found to be biocompatible toward mouse
      fibroblasts (95% viability). The hydrogels were thoroughly characterized
      regarding their rheological properties indicating fast gel formation (<3 min) and
      moderate cross-linking (1.5% strain, G' = 10 Pa). Cooling (fridge conditions) was
      found to be the simple on/off switch of the enzymatic machinery which is of great
      importance regarding storage and applicability of the bioactive hydrogel. This
      robust and bioactive antimicrobial hydrogel system overcomes dosing issues of
      common topical wound treatments and constitutes a promising wound healing
      approach for the future.

PMID- 28429929
TI  - Flexible Paper-like Free-Standing Electrodes by Anchoring Ultrafine SnS2
      Nanocrystals on Graphene Nanoribbons for High-Performance Sodium Ion Batteries.
AB  - Ultrafine SnS2 nanocrystals-reduced graphene oxide nanoribbon paper (SnS2-RGONRP)
      has been created by a well-designed process including in situ reduction,
      evaporation-induced self-assembly, and sulfuration. The as-formed SnS2
      nanocrystals possess an average diameter of 2.3 nm and disperse on the surface of
      RGONRs uniformly. The strong capillary force formed during evaporation leads to a
      compact assembly of RGONRs to give a flexible paper structure with a high density
      of 0.94 g cm-3. The as-prepared SnS2-RGONRP composite could be directly used as
      free-standing electrode for sodium ion batteries. Due to the synergistic effects
      between the ultrafine SnS2 nanocrystals and the conductive, tightly connected
      RGONR networks, the composite paper electrode exhibits excellent electrochemical
      performance. A high volumetric capacity of 508-244 mAh cm-3 was obtained at
      current densities in the range of 0.1-10 A g-1. Discharge capacities of 334 and
      255 mAh cm-3 were still kept, even after 1500 cycles tested at current densities
      of 1 and 5 A g-1, respectively. This strategy provides insight into a new pathway
      for the creation of free-standing composite electrodes used in the energy storage
      and conversion.

PMID- 28429930
TI  - Enzymatically Debranched Xylans in Graft Copolymerization.
AB  - Wheat arabinoxylan was treated with two alpha-arabinofuranosidases exhibiting
      different mode of action to create three different polymeric substrates. These
      three substrate preparations were characterized by xylopyranose backbone sugars
      that are (1) singly substituted by arabinose at C2 or C3, (2) doubly substituted
      by arabinose at C2 and C3, and (3) largely unsubstituted. All xylan preparations
      were grafted with glycidyl methacrylate using cerium ammonium nitrate and then
      evaluated in terms of graft yield and adsorption to cellulose surfaces. The
      highest graft yield was observed for the xylan preparation characterized by a
      largely unsubstituted xylopyranose backbone. Furthermore, QCM-D analyses revealed
      that grafted xylans exhibited a two-stage desorption pattern, which was not seen
      with the ungrafted xylans and was consistent with increased water sorption.
      Accordingly, this study demonstrates the potential of arabinofuranosidases to
      increase the yield and influence the viscoelastic properties of grafted xylans
      used as biobased cellulose coatings.

PMID- 28429931
TI  - Heterobimetallic Nitrido Complexes of Group 8 Metalloporphyrins.
AB  - Heterobimetallic nitrido porphyrin complexes with the [(L)(por)M-N-M'(LOEt)Cl2]
      formula {por2- = 5,10,15,20-tetraphenylporphyrin (TPP2-) or 5,10,15,20-tetra(p
      tolyl)porphyrin (TTP2-) dianion; LOEt- = [Co(eta5-C5H5){P(O)(OEt)2}3]-; M = Fe,
      Ru, or Os; M' = Ru or Os; L = H2O or pyridine} have been synthesized, and their
      electrochemistry has been studied. Treatment of trans-[Fe(TPP)(py)2] (py =
      pyridine) with Ru(VI) nitride [Ru(LOEt)(N)Cl2] (1) afforded Fe/Ru MU-nitrido
      complex [(py)(TPP)Fe(MU-N)Ru(LOEt)Cl2] (2). Similarly, Fe/Os analogue
      [(py)(TPP)Fe(MU-N)Os(LOEt)Cl2] (3) was obtained from trans-[Fe(TPP)(py)2] and
      [Os(LOEt)(N)Cl2]. However, no reaction was found between trans-[Fe(TPP)(py)2] and
      [Re(LOEt)(N)Cl(PPh3)]. Treatment of trans-[M(TPP)(CO)(EtOH)] with 1 afforded MU
      nitrido complexes [(H2O)(TPP)M(MU-N)Ru(LOEt)Cl2] [M = Ru (4a) or Os (5)]. TTP
      analogue [(H2O)(TTP)Ru(MU-N)Ru(LOEt)Cl2] (4b) was prepared similarly from trans
      [Ru(TTP)(CO)(EtOH)] and 1. Reaction of [(H2O)(por)M(MU-N)M(LOEt)Cl2] with
      pyridine gave adducts [(py)(por)M(MU-N)Ru(LOEt)Cl2] [por = TTP, and M = Ru (6);
      por = TPP, and M = Os (7)]. The diamagnetism and short (por)M-N(nitride)
      distances in 2 [Fe-N, 1.683(3) A] and 4b [Ru-N, 1.743(3) A] are indicative of the
      MIV?N?M'IV bonding description. The cyclic voltammograms of the Fe/Ru (2) and
      Ru/Ru (4b) complexes in CH2Cl2 displayed oxidation couples at approximately +0.29
      and +0.35 V versus Fc+/0 (Fc = ferrocene) that are tentatively ascribed to the
      oxidation of the {LOEtRu} and {Ru(TTP)} moieties, respectively, whereas the Fe/Os
      (3) and Os/Ru (5) complexes exhibited Os-centered oxidation at approximately 
      0.06 and +0.05 V versus Fc+/0, respectively. The crystal structures of 2 and 4b
      have been determined.

PMID- 28429933
TI  - Remarkably Enhancing Green-Excitation Efficiency for Solar Energy Utilization:
      Red Phosphors Ba2ZnS3:Eu2+, X- Co-Doped Halide Ions (X = Cl, Br, I).
AB  - Eu2+-activated Ba2ZnS3 has been reported as a red phosphor with a broad emission
      band peaking at 650 nm under blue excitation for white-LED. In this study,
      Ba2ZnS3:Eu2+, X- (X = F, Cl, Br, I) phosphors doped with halide ions were
      prepared by traditional high-temperature solid-state reaction. Phase
      identification of powders was performed by X-ray powder diffraction analysis,
      confirming the existence of single-phase Ba2ZnS3 crystals without dopant. The
      corresponding excitation spectra showed an additional broad band in the green
      region peaking at 550 nm when the phosphor was halogenated except by the smallest
      F-. It was proved that the green-excitation efficiency successively strengthened
      from Cl-, to Br-, to I-, which suggested larger halide ions made a greater
      contribution to the further splitting of the t2g energy level of the doped Eu2+
      ions in the host Ba2ZnS3, and the optimized formula Ba1.995ZnS2.82:Eu2+0.005, I
      0.18 showed a potential application in solar spectral conversion for agricultural
      greenhouse and solar cell. Defect chemistry theory and crystal field theory
      provided insights into the key role of halide ions in enhancing green-excitation
      efficiency.

PMID- 28429932
TI  - Thermodynamics of the Thermal Denaturation of Acid Molten Globule State of
      Cytochrome c Indicate a Reversible High-Temperature Oligomerization Process.
AB  - In this study, we performed differential scanning calorimetry (DSC) and pressure
      perturbation calorimetry (PPC) analysis of the thermal transition of cytochrome c
      from an acidic molten globule (MG) state with the protein concentrations of 0.5
      18.2 mg/mL. DSC profiles were highly reversible and showed clear protein
      concentration dependence, indicating that reversible oligomerization occurred
      accompanying the thermal transition from the MG state. The DSC and PPC data
      required at least a six-state model (MG1 ? MG2 ? D ? 1/2 I2 ? 1/3 I3 ? 1/4 I4)
      including three new oligomeric states: dimer (I2), trimer (I3), and tetramer (I4)
      in addition to the three monomeric states previously characterized. Dynamic light
      scattering confirmed the oligomerization during the thermal transition. The
      partial specific volumes of these oligomeric states were found to be smaller than
      those of the monomeric states, MG2 and D, indicating dehydration of hydrophobic
      surface or hydration of released anions may occur with the reversible
      oligomerization.

PMID- 28429934
TI  - Bi4TaO8Cl Nano-Photocatalyst: Influence of Local, Average, and Band Structure.
AB  - The average structure, local structure, and band structure of nanoparticles of
      photocatalyst Bi4TaO8Cl, an Aurivillius-Sillen layered material, has been studied
      by powder neutron Rietveld refinement, neutron pair distribution function
      technique, Raman scattering, and density functional theory calculations. A
      significant local structural deviation of nano-Bi4TaO8Cl was established in
      contrast to the local structure of bulk-Bi4TaO8Cl. Local structure was further
      supported by Raman scattering measurements. Through DFT calculations, we identify
      specific features in the electronic band structure that correlate lower secondary
      structural distortions in nano-Bi4TaO8Cl. Increased distortion of TaO6, decreased
      Ta-O-Ta bond angle, and increased octahedral tilt in the local structure of nano
      Bi4TaO8Cl influence the band structure and the electron hole pair migration.
      Therefore, in addition to morphology and size, the local structure of a
      nanomaterial contributes to the photocatalytic performance. Trapping experiments
      confirm the role of superoxide radical in the photocatalysis mechanism of this
      material. Such studies help in developing new functional materials with better
      photocatalytic efficiency to address energy and environmental issues.

PMID- 28429935
TI  - Saponins (Ginsenosides) from the Leaves of Panax quinquefolius Ameliorated
      Acetaminophen-Induced Hepatotoxicity in Mice.
AB  - Acetaminophen (APAP) overdose is one of the most common inducements of drug
      induced liver injury (DILI) in the world. The main purpose of this paper was to
      investigate the liver protection activity of saponins (ginsenosides) from the
      leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity, and the
      involved mechanisms were demonstrated for the first time. Mice were pretreated
      with PQS (150 and 300 mg/kg) by oral gavage for 7 days before being treated with
      250 mg/kg APAP. Severe liver injury was exerted at 24 h post-APAP, and
      hepatotoxicity was assessed. Our results showed that pretreatment with PQS
      significantly decreased the serum alanine aminotransferase (ALT), aspartate
      transaminase (AST), tumor necrosis factor (TNF-alpha), and interleukin-1beta (IL
      1beta) levels in a dose-dependent manner as compared to the APAP administration.
      Meanwhile, compared with that in the APAP group, PQS decreased hepatic
      malondialdehyde (MDA) contents and 4-hydroxynonenal (4-HNE) expression and
      restored reduced glutathione (GSH) content and superoxide dismutase (SOD)
      activity in livers of mice. PQS inhibited the overexpression of pro-inflammatory
      factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in
      the liver tissues. Furthermore, Western blotting analysis revealed that PQS
      pretreatment inhibited the activation of apoptotic signaling pathways via
      increase of Bcl-2 and decrease of Bax and caspase-3 protein expression levels.
      Liver histopathological observation provided further evidence that PQS
      pretreatment significantly inhibited APAP-induced hepatocyte necrosis,
      inflammatory cell infiltration, and congestion. Biological indicators of
      nitrative stress such as 3-nitrotyrosine (3-NT) were inhibited after PQS
      pretreatment, compared to the APAP group. The present study clearly demonstrates
      that PQS exerts a protective effect against APAP-induced hepatic injury because
      of its antioxidant, anti-apoptotic, and anti-inflammatory activities. The
      findings from the present investigation show that PQS might be a promising
      candidate treatment agent against drug-induced ALI.

PMID- 28429936
TI  - Electron Decoupling with Dynamic Nuclear Polarization in Rotating Solids.
AB  - Dynamic nuclear polarization (DNP) can enhance NMR sensitivity by orders of
      magnitude by transferring spin polarization from electron paramagnetic resonance
      (EPR) to NMR. However, paramagnetic DNP polarizing agents can have deleterious
      effects on NMR signals. Electron spin decoupling can mitigate these paramagnetic
      relaxation effects. We demonstrate electron decoupling experiments in conjunction
      with DNP and magic-angle-spinning NMR spectroscopy. Following a DNP and spin
      diffusion period, the microwave irradiation frequency is quickly tuned on
      resonance with electrons on the DNP polarizing agent. The electron decoupling
      performance shows a strong dependence on the microwave frequency and DNP
      polarization time. Microwave frequency sweeps through the EPR line shape are
      shown as a time domain strategy to significantly improve electron decoupling. For
      13C spins on biomolecules frozen in a glassy matrix, electron decoupling reduces
      the line widths by 11% (47 Hz) and increases the intensity by 14%.

PMID- 28429937
TI  - Total Synthesis of Two Glycosylated Stilbenes, Oxyresveratrol 2-O-beta-d
      Glucopyranoside and 2,3,5,4'-Tetrahydroxystilbene 2-O-beta-d-Glucopyranoside.
AB  - Glycosylated stilbenes are biologically active secondary metabolites of plants
      and have the potential to alleviate a broad range of human diseases. However,
      some of these compounds are not naturally abundant, and thus the synthesis of
      such molecules is desirable. This paper reports the first synthesis of
      oxyresveratrol 2-O-beta-d-glucopyranoside (1) and 2,3,5,4'-tetrahydroxystilbene 2
      O-beta-d-glucopyranoside (1'), which are stilbene glycosides obtained from the
      rhizomes of Schoenocaulon officinale and Polygonum multiflorum, respectively. A
      facile four-step synthesis of 1 involved selective protection of the hydroxy
      groups and Wittig olefination to generate the compound in 8% overall yield. For
      compound 1', a 10-step synthesis utilized selective protection of the hydroxy
      groups, Baeyer-Villiger oxidation, modified Duff formylation, and Wittig
      olefination to generate the compound in 6.9% overall yield.

PMID- 28429938
TI  - High-Resolution Accurate-Mass Mass Spectrometry Enabling In-Depth
      Characterization of in Vivo Biotransformations for Intact Antibody-Drug
      Conjugates.
AB  - Antibody-drug conjugates (ADCs) represent a promising class of therapeutics for
      the targeted delivery of highly potent cytotoxic drugs to tumor cells to improve
      bioactivity while minimizing side effects. ADCs are composed of both small and
      large molecules and therefore have complex molecular structures. In vivo
      biotransformations may further increase the complexity of ADCs, representing a
      unique challenge for bioanalytical assays. Quadrupole-time-of-flight mass
      spectrometry (Q-TOF MS) with electrospray ionization has been widely used for
      characterization of intact ADCs. However, interpretation of ADC
      biotransformations with small mass changes, for the intact molecule, remains a
      limitation due to the insufficient mass resolution and accuracy of Q-TOF MS.
      Here, we have investigated in vivo biotransformations of multiple site-specific
      THIOMAB antibody-drug conjugates (TDCs), in the intact form, using a high
      resolution, accurate-mass (HR/AM) MS approach. Compared with conventional Q-TOF
      MS, HR/AM Orbitrap MS enabled more comprehensive identification of ADC
      biotransformations. It was particularly beneficial for characterizing ADC
      modifications with small mass changes such as partial drug loss and hydrolysis.
      This strategy has significantly enhanced our capability to elucidate ADC
      biotransformations and help understand ADC efficacy and safety in vivo.

PMID- 28429939
TI  - Solute Rotation in Ionic Liquids: Size, Shape, and Electrostatic Effects.
AB  - Herein are reported temperature-dependent measurements and molecular dynamics
      simulations designed to investigate the effects of molecular size, shape, and
      electrostatics on rotational dynamics in ionic liquids. Experiments were
      performed in the representative ionic liquid 1-butyl-3-methylimadazolium
      tetrafluoroborate ([Im41][BF4]) and simulations in the generic ionic liquid model
      ILM2 as well as a more detailed representation of [Im41][BF4]. 2H longitudinal
      spin relaxation times (T1) were measured for deuterated versions of 1,4
      dimethylbenzene, 1-cyano-4-methylbenzene, and 1,4-dimethylpyridinium between 296
      and 337 K. Fluorescence anisotropy measurements were made on the larger solutes
      9,10-dimethylanthracene, 9-cyano-10-methylanthracence, and 9,10-dimethylacridnium
      between 240 and 292 K. Both experiment and simulation showed the nonpolar solutes
      rotate ~2-fold faster than their dipolar and charged counterparts. The rotational
      correlation functions measured in fluorescence experiments are significantly
      nonexponential and can be fit to stretched exponential functions having
      stretching exponents 0.4 <= beta <= 0.8, with beta decreasing with decreasing
      temperature. Rotational correlation times in both the NMR and fluorescence
      experiments conform approximately to the hydrodynamic expectation taurot ?
      (eta/T)p with p ? 1, and observed times are reasonably close to slip hydrodynamic
      predictions. Simulations, even with the idealized ILM2 solvent model, are in
      semiquantitative agreement with experiment when compared on the basis of equal
      values of etaT-1. When rotational diffusion coefficients (Di) rather than
      correlation times were considered, much larger departures from hydrodynamic
      predictions are found in many cases (p ~ 0.5 and Di ? slip predictions).
      Rotational van Hove functions and trajectory analyses reveal the importance of
      large-angle jumps about some axes, even in the larger solutes.

PMID- 28429940
TI  - Density Functional Theory and Car-Parrinello Molecular Dynamics Study of the
      Hydrogen-Producing Mechanism of the Co(dmgBF2)2 and Co(dmgH)2 Cobaloxime
      Complexes in Acetonitrile-Water Solvent.
AB  - The catalytic hydrogen-producing processes of two prototypical cobaloxime
      catalysts, Co(dmgBF2)2 (dmgBF2 = difluoroboryl-dimethylglyoxime) and Co(dmgH)2
      (dmgH = dimethylglyoxime), were studied by density functional theory (DFT) and
      Car-Parrinello molecular dynamics (CPMD) simulations in the explicit acetonitrile
      water solvent. Our study demonstrates the key role of water molecules as shuttles
      to deliver protons to the cobalt active centers of these catalysts. However, the
      transfer of protons to the cobalt centers also competes with the diffusion of the
      proton away from the complex via the hydrogen bond network of water. Protons were
      found to react with the oxygen of the side group of Co(dmgH)2, while a similar
      reaction was not observed for Co(dmgBF2)2. This explains the experimentally
      observed relative instability of Co(dmgH)2 in the acidic medium. The rate
      limiting step of the hydrogen-producing process was found to be the first proton
      transfer to the cobalt center for both cobaloxime complexes. Structural and
      electron population analysis was carried out to provide insight into the origin
      of the difference of the proton transfer free-energy barriers of these two cobalt
      complexes. Our study has contributed to the key microscopic understanding of the
      hydrogen-producing process by this class of catalysts.

PMID- 28429941
TI  - Selective Phosphoramidation and Phosphonation of Benzoxazoles via Sequence
      Control.
AB  - A selective phosphoramidation and phosphonation of benzoxazole was developed with
      trialkyl phosphites in the presence of iodine under mild conditions. In the
      reaction, the transformation completes in 10 min at room temperature and the
      substrates are well tolerant, as 2-substituted azoles could afford the quaternary
      carbon-centered products. Significantly, phosphites could be selectively
      introduced into the C- and N-positions of the benzoxazoles by controlling the
      addition sequence and the ratio of substrates.

PMID- 28429942
TI  - Layer Polarizability and Easy-Axis Quantum Hall Ferromagnetism in Bilayer
      Graphene.
AB  - We report magnetotransport measurements of graphene bilayers at large
      perpendicular electric displacement fields, up to ~1.5 V/nm, where we observe
      crossings between Landau levels with different orbital quantum numbers. The
      displacement fields at the studied crossings are primarily determined by energy
      shifts originating from the Landau level layer polarizability or polarization.
      Despite decreasing Landau level spacing with energy, successive crossings occur
      at larger displacement fields, resulting from decreasing polarizability with
      orbital quantum number. For particular crossings we observe resistivity
      hysteresis in displacement field, indicating the presence of a first-order
      transition between states exhibiting easy-axis quantum Hall ferromagnetism.

PMID- 28429943
TI  - Size and Origins of Long-Range Orientational Water Correlations in Dilute Aqueous
      Salt Solutions.
AB  - Long-range ordering of water around solutes has been repeatedly invoked as the
      key to its biological function. Recently, it has been shown that in an 8 mM
      aqueous NaCl solution the orientational correlation between water molecules
      extends beyond 8 nm. This was interpreted as arising from ion-induced long-range
      effects on the water collective hydrogen-bond interactions. Each ion was
      suggested to affect >10 000 water molecules, leading to a picture involving
      nanoscopic "ordered domains". Using molecular dynamics simulations, we show that
      the very small long-range tail in the correlation function is caused primarily by
      pairs of water molecules belonging to different ions' hydration shells and can be
      made to practically disappear by rearranging the ionic positions. This means that
      the ion-induced water orientational ordering in millimolar salt solutions cannot
      be separated from ion-ion interaction effects, for which the Debye-Huckel
      screening length shrinks to less than 1 nm at physiological ionic strengths.

PMID- 28429944
TI  - Biotechnological Production of Dimethoxyflavonoids Using a Fusion Flavonoid O
      Methyltransferase Possessing Both 3'- and 7-O-Methyltransferase Activities.
AB  - Although they are less abundant in nature, methoxyflavonoids have distinct
      physicochemical and pharmacological properties compared to common nonmethylated
      flavonoids. Thus, enzymatic conversion and biotransformation using genetically
      engineered microorganisms of flavonoids have been attempted for the efficient
      production of methoxyflavonoids. Because of their regiospecificity, more than two
      flavonoid O-methyltransferases (FOMTs) and enzyme reactions are required to
      biosynthesize di(or poly)-methoxyflavonoids. For the one-step biotechnological
      production of bioactive di-O-methylflavonoids, we generated a multifunctional
      FOMT fusing a 3'-OMT (SlOMT3) and a 7-OMT (OsNOMT). The SlOMT3/OsNOMT fusion
      enzyme possessed both 3'- and 7-OMT activities to diverse flavonoid substrates,
      which were comparable to those of individual SlOMT3 and OsNOMT. The SlOMT3/OsNOMT
      enzyme also showed 3'- and 7-OMT activity for 7- or 3'-O-methylflavonoids,
      respectively, suggesting that the fusion enzyme can sequentially methylate
      flavonoids into di-O-methylflavonoids. The biotransformation of the flavonoids
      quercetin, luteolin, eriodictyol, and taxifolin using SlOMT3/OsNOMT-transformed
      Escherichia coli generated corresponding di-O-methylflavonoids, rhamnazin,
      velutin, 3',7-di-O-methyleriodictyol, and 3',7-di-O-methyltaxifolin,
      respectively. These results indicate that dimethoxyflavonoids may be efficiently
      produced from nonmethylated flavonoid precursors through a one-step
      biotransformation using the engineered E. coli harboring the SlOMT3/OsNOMT fusion
      gene.

PMID- 28429945
TI  - Copper-Catalyzed Oxidative Cyclization of 2-Amino-azaarenes with Lignin Models:
      Synthesis of 3-Phenoxy Imidazo Heterocycles.
AB  - A catalytic oxidative cyclization of 2-aminopyridines or 2-aminobenzothiazole
      with 2-phenoxyacetophenones (a kind of lignin platform compound) was developed,
      efficiently providing valuable 3-phenoxy imidazo[1,2-a]pyridines or 3-phenoxy
      benzo[d]imidazo[2,1-b]thiazoles. The reaction was realized under oxygen by simply
      using inexpensive CuI as the catalyst.

PMID- 28429946
TI  - Ag-Catalyzed Intramolecular Sequential Vicinal Diamination of Alkynes with
      Isocyanates: Synthesis of Fused Indole-Cyclic Urea Derivatives.
AB  - A formal intramolecular vicinal 1,2-diamination of alkynes is achieved for the
      synthesis of indole-cyclic urea fused derivatives through a double cyclization
      process from readily available aminophenyl propargyl alcohols. This sequential
      triple C-N bond construction event was possible using isocyanate as urea
      precursor and Ag(I) catalyst as alkyne activating agent. Control experiments
      reveal that the cyclization, followed by 1,3-allylic amino dehydroxylation, is
      preceded by urea formation.

PMID- 28429947
TI  - A practical guide to development of a successful robotic abdominal surgery
      program: The path to implementation.
AB  - The authors describe current situation in robotic assisted operations. The most
      important aspects of establishing a successful robotic program are patience and
      flexibility. The improved patient satisfaction, return to function, and decreased
      perioperative pain for patients and surgeons will be seen, but the road is long
      and requires careful navigation.Key Words: robot abdominal surgery - program
      development.

PMID- 28429948
TI  - [Robotic surgery in gynecology].
AB  - INTRODUCTION: The aim of this review is to provide a general historical and
      contemporary perspective on the implementation and use of robot-assisted
      laparoscopy in gynecology as well as the experience gained to date. CONTENTS:
      Robotic-assisted laparoscopic surgeries in gynecology include benign
      hysterectomy, myomectomy, radical hysterectomy, lymph node dissections or
      sacrocolpopexies. Robot-assisted gynecologic surgery is often associated with
      longer operating room time but generally similar clinical outcomes, decreased
      blood loss and shorter hospital stay when compared to open or laparoscopic
      surgery. CONCLUSIONS: Robotic surgery is associated with a shorter learning curve
      and has allowed a larger number of gynecologists to master complex laparoscopic
      procedures. Robot-assisted surgery offers all the benefits of minimally invasive
      surgery, making them accessible to a much broader spectrum of patients.Key words:
      robotic surgery - gynecology hysterectomy - da Vinci laparoscopy.

PMID- 28429949
TI  - [The da Vinci robot in the field of vascular surgery].
AB  - INTRODUCTION: The aim of this study was to evaluate the clinical experience with
      379 robot-assisted vascular procedures performed from November 2005 to December
      2016 at our institution. METHODS: A total of 366 cases (96.6%) were successfully
      completed using the robotic surgical systems da Vinci Standard and da Vinci Xi.
      RESULTS: Conversion was necessary in 13 patients (3.4%). The 30-day mortality was
      0.26% and 2 (0.5%) late prosthetic infections occurred. CONCLUSIONS: From a
      practical point of view, the greatest advantage of robot-assisted procedures has
      been the speed and relative simplicity of vascular anastomosis construction. Our
      experience with robot-assisted surgery has demonstrated the safety and
      feasibility of this technique in different areas of vascular surgery.Key words:
      robotic vascular surgery aortic and non-aortic surgery.

PMID- 28429950
TI  - [Can robotic rectal cancer surgery improve quality of total mesorectal excision?]
AB  - INTRODUCTION: The introduction of total mesorectal excision (TME) in the 1980s
      was pivotal in the surgical treatment for rectal carcinoma (RC). Routinely
      applied TME led to a significant reduction in the incidence of local recurrences.
      The purpose of our paper is to present the results of our non-randomized study
      comparing prospectively acquired data from radical resection / rectal extirpation
      using classic open access, laparoscopy and da Vinci robotic system. METHOD: The
      study group included 116 patients with RC who underwent radical surgical
      treatment between 1/2014-12/2016, after which the collected resection specimens
      were assessed in pathology laboratories of the referring hospital using the
      Quirkes protocol. Analysis of data collected prospectively over a period of 3
      years was done. The surgical procedures were open, laparoscopic and robotic.
      Robotic surgery could only be performed in patients whose health insurers
      guaranteed to cover the robotic resection expenses. Those patients whose health
      insurers did not cover the costs of the robotic assisted procedure were treated
      using the laparoscopic technique. RESULTS: Over a period of 3 years (2014-2016),
      the teams at the Department of Surgery of the 2nd Faculty of Medicine, Charles
      University and Central Military Hospital, Prague treated 116 patients (75 men and
      41 women) for RC; resected specimens of the patients were processed according to
      the Quirkes protocol. Mean age was 63 years (33-80). pCRO positivity was
      confirmed in 5 patients (4.3%) and complete or nearly complete TME was achieved
      in 94 patients (81%). More than a half of the procedures were performed using the
      minimally invasive surgery. No patient died. CONCLUSION: Despite the high rate of
      technically difficult cases (male sex, tumours in the distal third of the
      rectum), the robotic assisted treatment showed best results in our study group in
      terms of quality of the mesorectal excision. Our results thus provide evidence of
      an unequivocal benefit of robotic assistance compared to manual laparoscopy and
      open procedures in terms of TME as a quality indicator of surgery in patients
      with CR. Given the limited time span, there are no long-term results to be
      assessed in our patients.Key words: rectal carcinoma - TME - evaluation of
      surgical treatment - robotic rectal surgery.

PMID- 28429951
TI  - [Robotic-assisted radical prostatectomy - results of 1500 surgeries].
AB  - INTRODUCTION: Prostate cancer is the most common malignant disease in men. The
      number of cases of prostate cancer has increased dramatically in recent 20 years.
      Radical prostatectomy is a surgical method for the first-line treatment of
      localised prostate cancer. We performed the first robotic-assisted radical
      prostatectomy on December 16th, 2005, achieved the boundary of 1000 robotic
      assisted radical prostatectomies in 2012, and in 2015, we successfully completed
      the 1500th robotic-assisted operation on the prostate. METHOD: We retrospectively
      evaluated the oncological and functional results in 1,500 consecutive patients
      who underwent robotic-assisted radical prostatectomy at our institution between
      20052015. The robotic system da Vinci Standard was used for the operations until
      November 2013, and subsequently the robotic system da Vinci Si HD. Mean age of
      the patients was 63.7 years (40 to 86); mean BMI was 27.7 (19.4 to 41.4); and
      mean preoperative PSA was 6.7 ng/ml (0.4 to 112.0). RESULTS: Pathological stage
      of the localised prostate cancer was found in 1125 (75%) men, and the stage of
      locally advanced cancer was found in 363 (24.2%) patients. We determined the
      Gleason score 7 in surgical specimens of 1150 (76.7%) men. 171 (11.4%) men
      underwent pelvic lymphadenectomy; metastases in the pelvic lymph nodes were
      detected in 36 (21.1%) patients. Urinary continence in the period of up to 1 year
      after the surgery was evaluated in 1218 (81.2%) patients in the group. 1119
      (91.9%) men needed no incontinence pads or one safety pad one year from the
      surgery. Postoperative erectile function was evaluated in 447 (29.8%) men. One
      year from the surgery, 247 (55.3%) men were capable of a sufficient erection for
      sexual intercourse without any supportive therapy. Intraoperative complications
      according to the Clavien-Dindo classification were observed in 20 (1.3%)
      patients; complications within 3 months from the surgery were observed in 127
      (8.5%) patients. CONCLUSION: Robotic-assisted radical prostatectomy is a clearly
      defined, safe and reproducible minimally invasive treatment of localised prostate
      cancer.Key words: prostate cancer robotic surgery radical prostatectomy
      complications.

PMID- 28429953
TI  - [Popliteal vein aneurysm].
AB  - Popliteal vein aneurysm is a rare disease of the lower limb venous system.
      Massive pulmonary embolism may be a clinically serious presentation of the
      disease. The authors present surgical management of the popliteal vein aneurysm
      in two case reports.Key words: popliteal vein aneurysm surgical management.

PMID- 28429952
TI  - Rare cases imitating acute appendicitis: Three case reports and a review of
      literature.
AB  - Acute appendicitis with its characteristic clinical course is one of the most
      common diagnoses that require urgent surgery. The following three case reports
      present patients with symptoms typical of acute appendicitis which was, however,
      not confirmed intraoperatively. Preoperative CT or MRI were not requested because
      symptoms clearly indicated acute appendicitis. The first case describes a male
      patient with right-sided diverticulitis, the second case report involves a
      pregnant woman in 33rd week of gestation with right adnexal torsion due to a
      dermoid cyst, and in the last report, a case of spontaneous perforation of
      appendiceal mucinous neoplasm is presented.Key words: right-sided diverticulitis 
      dermoid cyst - adnexal torsion - mucinous neoplasm - pseudomyxoma peritonei -
      appendicitis.

PMID- 28429954
TI  - [Sternal resection for metachronous metastasis from renal carcinoma].
AB  - In this report, the authors describe a rare case of complete sternal resection
      for a metachronous metastasis from renal carcinoma in a 59-year-old female
      patient 12 years after primary left nephrectomy. Due to the large extent of
      resection, a polyester double layer mesh with bone cement was used for chest wall
      reconstruction. The postoperative course was uneventful without any indication
      for adjuvant treatment. The patient has been followed up for 20 months without
      any signs of complications and recurrence of her malignancy.Key words: sternum
      resection bone metastases renal carcinoma.

PMID- 28429955
TI  - Matrix metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1
      predict incident cardiovascular disease events and all-cause mortality in a
      population-based cohort.
AB  - Background Extracellular matrix degrading proteases and their regulators play an
      important role in atherogenesis and subsequent plaque rupture leading to acute
      cardiovascular manifestations. Design and methods In this prospective cohort
      study, we investigated the prognostic value of circulating matrix
      metalloproteinase-8, tissue inhibitor of matrix metalloproteinase-1
      concentrations, the ratio of matrix metalloproteinase-8/ tissue inhibitor of
      matrix metalloproteinase-1 and, for comparison, myeloperoxidase and C-reactive
      protein concentrations for incident cardiovascular disease endpoints. The
      population-based FINRISK97 cohort comprised 7928 persons without cardiovascular
      disease at baseline. The baseline survey included a clinical examination and
      blood sampling. During a 13-year follow-up the endpoints were ascertained through
      national healthcare registers. The associations of measured biomarkers with the
      endpoints, including cardiovascular disease event, coronary artery disease, acute
      myocardial infarction, stroke and all-cause death, were analysed using Cox
      regression models. Discrimination and reclassification models were used to
      evaluate the clinical implications of the biomarkers. Results Serum tissue
      inhibitor of matrix metalloproteinase-1 and C-reactive protein concentrations
      were associated significantly with increased risk for all studied endpoints.
      Additionally, matrix metalloproteinase-8 concentration was associated with the
      risk for a coronary artery disease event, myocardial infarction and death, and
      myeloperoxidase concentration with the risk for cardiovascular disease events,
      stroke and death. The only significant association for the matrix
      metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 ratio was
      observed with the risk for myocardial infarction. Adding tissue inhibitor of
      matrix metalloproteinase-1 to the established risk profile improved risk
      discrimination of myocardial infarction ( p=0.039) and death (0.001). Both matrix
      metalloproteinase-8 (5.2%, p < 0.001) and tissue inhibitor of matrix
      metalloproteinase-1 (12.9%, p < 0.001) provided significant clinical net
      reclassification improvement for death. Conclusions Serum matrix
      metalloproteinase-8 and tissue inhibitor of matrix metalloproteinase-1 can be
      considered as biomarkers of incident cardiovascular disease events and death.

PMID- 28429956
TI  - Efficacy of piezocision on accelerating orthodontic tooth movement: A systematic
      review.
AB  - OBJECTIVES: The aim of this systematic review was to evaluate the effect of
      piezocision as an adjunctive procedure to accelerate orthodontic tooth movement.
      MATERIALS AND METHODS: Randomized controlled trials and controlled clinical
      trials that investigated the effectiveness of piezocision on accelerating
      orthodontic tooth movement were identified through electronic and manual
      searches. The literature search, study inclusion, risk of bias assessment, and
      data extraction were performed by two reviewers independently. RESULTS: Four
      eligible studies were included in this review. All studies reported accelerated
      tooth movement after piezocision, and three reported a significant reduction of
      treatment duration in the piezocision group. No deleterious effects on
      periodontal status, pain perception, satisfaction, root resorption, or anchorage
      control were reported in any studies. CONCLUSION: Based on currently available
      information, weak evidence supports that piezocision is a safe adjunct to
      accelerate orthodontic tooth movement, at least in the short term. More high
      quality clinical trials to determine the long-term effects and optimal protocol
      for piezocision are needed to draw more reliable conclusions.

PMID- 28429957
TI  - Utility of simplicity for low-risk chest pain patients.

PMID- 28429959
TI  - Reduced arteriovenous oxygen difference in heart failure with preserved ejection
      fraction patients: Is the muscle oxidative phenotype certainly involved?

PMID- 28429958
TI  - The Influence of Violence Victimization on Sexual Health Behaviors and Outcomes.
AB  - This study examines the implications of a history of personal violence on health
      and health behaviors. A secondary analysis of cross-sectional data involving
      adults (n = 214) from a semirural area in southern Louisiana between October 2008
      and December 2010 was conducted to ascertain the association between a personal
      history of violence victimization and indicators of sexual health behaviors and
      outcomes: communication with sexual partners about HIV status, consistent condom
      use, and sexually transmitted infection (STI). While violence victimization is
      widely accepted as a risk factor for high-risk sex behavior, the mechanisms
      underlying violence victimization's influence on sexual health outcomes remain
      unclear. Bivariate analyses demonstrated a significant positive association
      between experience of physical abuse and lifetime history of STI. Surprisingly,
      respondents reporting lifetime physical violence were more than two times more
      likely to ask sexual partners about HIV status [odds ratio (OR) for physical
      attack = 2.23, 95% confidence intervals (CI) = 1.00-4.97; OR for physical injury
      = 4.60, 95% CI = 1.79-11.85]. Consistent condom use was not significantly
      associated with violence exposure in adjusted models. There was no evidence that
      communication with sexual partners mediated the relationship between experiences
      of violence and condom use. The link between personal history of violence and
      condom use may be mediated through alternative pathways beyond communication.

PMID- 28429960
TI  - Extracellular matrix markers and risk of myocardial infarction: The HUNT Study in
      Norway.
AB  - Aims Extracellular matrix remodelling may influence atherosclerotic progression
      and plaque stability. We hypothesized that evaluation of extracellular matrix
      markers, with potentially different roles during atherogenesis, could provide
      information on underlying mechanisms and risk of myocardial infarction (MI) in
      apparently healthy individuals. Methods We conducted a case-control study nested
      within the population-based HUNT2 cohort in Norway. A total of 58,761 men and
      women, free of known cardiovascular disease, were followed for a first MI. During
      11.3 years of follow-up, 1587 incident MIs were registered, and these cases were
      compared with 3959 age- and sex-matched controls. Circulating levels of the ECM
      proteins CD147 (ECM metalloproteinase inducer; EMMPRIN), cartilage oligomeric
      matrix protein (COMP: thrombospondin-5) and YKL-40 (chitinase-3-like-1) were
      measured by enzyme immunoassays. Results We found an inverse association between
      COMP (quartile (Q) 4 vs. Q1: hazard ratio 0.81 (95% confidence interval: 0.67
      0.98)) and YKL-40 (Q4 vs. Q1: hazard ratio 0.77 (0.62-0.95)) with incidence of MI
      after full multivariable adjustment. Serum CD147 was not associated with MI risk
      in adjusted analysis. Conclusion High levels of COMP and YKL-40 were associated
      with lower risk of incident MI, suggesting a potential beneficial role in
      promoting plaque stability in individuals without incident cardiovascular
      disease.

PMID- 28429961
TI  - Analysis of Factors Relating to Companion Rabbits Relinquished to Two United
      Kingdom Rehoming Centers.
AB  - Rabbits are a common companion animal in the United Kingdom, and some reports
      have suggested that large numbers are relinquished to rehoming centers each year.
      This study aimed to investigate the characteristics of rabbits relinquished to 2
      UK rehoming centers and explore reasons given for relinquishment. The centers
      contributed data for all rabbits who entered their center during 2013 (n = 205).
      Most rabbits (59.5%) were relinquished by a guardian. Similar numbers of males
      and females were relinquished, and a larger number of rabbits were not neutered
      (72.4%) and adults (56%). Most rabbits were healthy on arrival (61.5%). The most
      common reasons for relinquishment were: "too many rabbits/unplanned litters"
      (30.3%) and "housing problems" (23.8%). Rabbit-related reasons accounted for
      12.2% of rabbits relinquished. Reasons for relinquishment were associated with 1
      of the recorded rabbit characteristics. Further detailed studies are needed to
      explore the dynamics of companion rabbit ownership and factors that affect the
      breakdown of rabbit-guardian relationships in the United Kingdom.

PMID- 28429963
TI  - Comment on "The Diagnostic Utility of Midcarpal Anesthetic Injection in the
      Evaluation of Chronic Wrist Pain."

PMID- 28429962
TI  - Predictors of restraint use among child occupants.
AB  - OBJECTIVES: The objective of this study was to identify factors that predict
      restraint use and optimal restraint use among children aged 0 to 13 years.
      METHODS: The data set is a national sample of police-reported crashes for years
      2010-2014 in which type of child restraint is recorded. The data set was
      supplemented with demographic census data linked by driver ZIP code, as well as a
      score for the state child restraint law during the year of the crash relative to
      best practice recommendations for protecting child occupants. Analysis used
      linear regression techniques. RESULTS: The main predictor of unrestrained child
      occupants was the presence of an unrestrained driver. Among restrained children,
      children had 1.66 (95% confidence interval, 1.27, 2.17) times higher odds of
      using the recommended type of restraint system if the state law at the time of
      the crash included requirements based on best practice recommendations.
      CONCLUSIONS: Children are more likely to ride in the recommended type of child
      restraint when their state's child restraint law includes wording that follows
      best practice recommendations for child occupant protection. However, state child
      restraint law requirements do not influence when caregivers fail to use an
      occupant restraint for their child passengers.

PMID- 28429964
TI  - Global mental health, autonomy and medical paternalism: reconstructing the
      'French ethical tradition' in psychiatry.
AB  - In the last few decades, the definition of deontological ethics, a well
      identified ethical territory in psychiatry, has been the object of increasing
      concerns. This has been the case in France, where claims of a specific ethical
      tradition in psychiatry have accompanied the institutionalization of psychiatric
      ethics and the perceived globalization of an Anglo-American model of mental
      health care. This study traces the history of the 'French ethical tradition in
      psychiatry' and its relationship with establishing institutional spaces for
      ethical decision-making. The 'ethical tradition' thus conceived proves to be
      functional in terms of preserving the threatened identity of French psychiatry.
      Nevertheless, this movement also pinpoints impasses that transcend the French
      context and may provide valuable resources for ethical reflections on mental
      health on a global scale.

PMID- 28429966
TI  - Abstracts and Posters Presented at the 2006 Annual Meeting of the American
      Association for Hand Surgery, Tucson, Arizona.

PMID- 28429965
TI  - Bayesian SEM for Specification Search Problems in Testing Factorial Invariance.
AB  - Specification search problems refer to two important but under-addressed issues
      in testing for factorial invariance: how to select proper reference indicators
      and how to locate specific non-invariant parameters. In this study, we propose a
      two-step procedure to solve these issues. Step 1 is to identify a proper
      reference indicator using the Bayesian structural equation modeling approach. An
      item is selected if it is associated with the highest likelihood to be invariant
      across groups. Step 2 is to locate specific non-invariant parameters, given that
      a proper reference indicator has already been selected in Step 1. A series of
      simulation analyses show that the proposed method performs well under a variety
      of data conditions, and optimal performance is observed under conditions of large
      magnitude of non-invariance, low proportion of non-invariance, and large sample
      sizes. We also provide an empirical example to demonstrate the specific
      procedures to implement the proposed method in applied research. The importance
      and influences are discussed regarding the choices of informative priors with
      zero mean and small variances. Extensions and limitations are also pointed out.

PMID- 28429968
TI  - Abstracts and Posters Presented at the 2007 Annual Meeting of the American
      Association for Hand Surgery, Rio Grande, Puerto Rico.

PMID- 28429967
TI  - Knee Arthroscopic Surgery in Middle-Aged Patients With Meniscal Symptoms: A 3
      Year Follow-up of a Prospective, Randomized Study.
AB  - BACKGROUND: The optimal treatment for middle-aged patients with knee pain and
      meniscal lesions has been extensively debated. Most previous studies have
      revealed only short-term beneficial results of knee arthroscopic surgery. The
      authors have previously shown a positive benefit of knee arthroscopic surgery and
      an exercise program after 1 year when compared with an exercise program alone.
      PURPOSE: To evaluate if knee arthroscopic surgery combined with an exercise
      program provided an additional long-term benefit after 3 years compared with an
      exercise program alone in middle-aged patients with meniscal symptoms. STUDY
      DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Of 179
      eligible patients, aged 45 to 64 years, 150 were randomized to (1) a 3-month
      exercise program (nonsurgery group) or (2) the same as group 1 plus knee
      arthroscopic surgery within 4 weeks (surgery group). The primary outcome was the
      change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscore of
      pain between baseline and the 3-year follow-up. Results from the 1-year follow-up
      have been published previously. RESULTS: Both treatment groups improved
      significantly in the KOOS pain subscore at 3 years' follow-up in the intention-to
      treat and as-treated analyses ( P < .001). The between-group difference for the
      change in the KOOS pain subscore between baseline and the 3-year follow-up was no
      longer statistically significant, neither in the intention-to-treat analysis (7.6
      points; 95% CI, -0.6 to 15.9; P = .068) nor in the as-treated analysis (5.3
      points; 95% CI, -3.1 to 13.8; P = .216). The factorial analysis of the effect of
      the intervention and age, onset of pain, and mechanical symptoms indicated that
      older patients improved more, regardless of treatment, and surgery may be more
      beneficial for patients without mechanical symptoms (as-treated analysis). The
      effect of the predictive factors on the KOOS pain subscore was uncertain because
      of the small sample size in the subgroup analyses. CONCLUSION: The benefit of
      knee arthroscopic surgery, seen at 1 year in middle-aged patients with meniscal
      symptoms, was diminished at 3 years and was no longer statistically significant.
      CLINICAL RELEVANCE: Knee arthroscopic surgery may be beneficial for middle-aged
      patients with meniscal symptoms in addition to an exercise program. Older age and
      absence of mechanical symptoms should not be contraindications to surgery.
      Registration: NCT01288768 ( ClinicalTrials.gov identifier).

PMID- 28429969
TI  - Advances in pharmacotherapeutic management of common skin diseases in neonates
      and infants.
AB  - INTRODUCTION: neonatal and infantile skin diseases are frequently encountered in
      the clinical practice and represent worldwide a socioeconomic issue. They
      encompass a wide range of acquired or congenital conditions, including
      infections, vascular lesions and inflammatory diseases and can present with
      different degrees of severity, leading in some cases to dramatic complications.
      Areas covered: In this paper we report the most recent evidences on the
      management of some common skin diseases in neonates and infants. Hemangiomas,
      viral, fungal and bacterial infections, omphalitis, atopic and seborrhoeic
      dermatitis, napkin disease will be treated and discussed. Expert opinion: The
      majority of the dermatologic alterations in neonates are physiological, transient
      and do not require any treatment, thus the parents can be reassured about the
      good prognosis. However, in some cases, serious conditions must be excluded. In
      particular neonatal and infantile infections should be promptly recognized and
      properly managed, to avoid severe complications. The therapeutic options include
      traditional and, although few, innovative medical treatments, which will be
      carefully taken into consideration by the expert Dermatologists and
      Paediatricians.

PMID- 28429970
TI  - Taking data seriously: the value of actor-network theory in rethinking patient
      experience data.
AB  - Hospitals are awash with patient experience data, much of it collected with the
      ostensible purpose of improving the quality of patient care. However, there has
      been comparatively little consideration of the nature and capacities of data
      itself. Using insights from actor-network theory, we propose that paying
      attention to patient experience data as having agency in particular hospital
      interactions allows us to better trace how and in what circumstances data lead
      (or fail to lead) to quality improvement.

PMID- 28429972
TI  - Impact case studies: mental health services for depression and anxiety.

PMID- 28429971
TI  - Evidence-based policy as reflexive practice. What can we learn from evidence
      based medicine?
AB  - The call for evidence-based policy is often accompanied by rather uncritical
      references to the success of evidence-based medicine, leading to often
      unsuccessful translation attempts. In this paper, I reflect on the practice of
      evidence-based medicine in an attempt to sketch a more productive approach to
      translating evidence into the practice of policy making. Discussing three
      episodes in the history of evidence-based medicine - clinical trials, and the
      production and use of clinical guidelines - I conclude that the success of
      evidence-based medicine is based on the creation of reflexive practices in which
      evidence and practice can be combined productively. In the conclusion, I discuss
      the prospects of such a practice for evidence-based policy.

PMID- 28429973
TI  - The role of paediatric nurses in medication safety prior to the implementation of
      electronic prescribing: a qualitative case study.
AB  - Objectives To explore paediatric nurses' experiences and perspectives of their
      role in the medication process and how this role is enacted in everyday practice.
      Methods A qualitative case study on a general surgical ward of a paediatric
      hospital in England, one year prior to the planned implementation of
      ePrescribing. Three focus groups and six individual semi-structured interviews
      were conducted, involving 24 nurses. Focus groups and interviews were audio
      recorded, transcribed, anonymized and subjected to thematic analysis. Results Two
      overarching analytical themes were identified: the centrality of risk management
      in nurses' role in the medication process and the distributed nature of nurses'
      medication risk management practices. Nurses' contribution to medication safety
      was seen as an intrinsic feature of a role that extended beyond just preparing
      and administering medications as prescribed and placed nurses at the heart of a
      dynamic set of interactions, practices and situations through which medication
      risks were managed. These findings also illustrate the collective nature of
      patient safety. Conclusions Both the recognized and the unrecognized
      contributions of nurses to the management of medications needs to be considered
      in the design and implementation of ePrescribing systems.

PMID- 28429974
TI  - The 'dark side' of knowledge brokering.
AB  - Deploying knowledge brokers to bridge the 'gap' between researchers and
      practitioners continues to be seen as an unquestionable enabler of evidence-based
      practice and is often endorsed uncritically. We explore the 'dark side' of
      knowledge brokering, reflecting on its inherent challenges which we categorize
      as: (1) tensions between different aspects of brokering; (2) tensions between
      different types and sources of knowledge; and (3) tensions resulting from the 'in
      between' position of brokers. As a result of these tensions, individual brokers
      may struggle to maintain their fragile and ambiguous intermediary position, and
      some of the knowledge may be lost in the 'in-between world', whereby research
      evidence is transferred to research users without being mobilized in their day-to
      day practice. To be effective, brokering requires an amalgamation of several
      types of knowledge and a multidimensional skill set that needs to be sustained
      over time. If we want to maximize the impact of research on policy and practice,
      we should move from deploying individual 'brokers' to embracing the collective
      process of 'brokering' supported at the organizational and policy levels.

PMID- 28429975
TI  - The real cost of training health professionals in Australia: it costs as much to
      build a dietician workforce as a dental workforce.
AB  - Objectives We explored the real cost of training the workforce in a range of
      primary health care professions in Australia with a focus on the impact of
      retention to contribute to the debate on how best to achieve the optimal health
      workforce mix. Methods The cost to train an entry-level health professional
      across 12 disciplines was derived from university fees, payment for clinical
      placements and, where relevant, cost of internship, adjusted for student drop
      out. Census data were used to identify the number of qualified professionals
      working in their profession over a working life and to model expected years of
      practice by discipline. Data were combined to estimate the mean cost of training
      a health professional per year of service in their occupation. Results General
      medical graduates were the most expensive to train at $451,000 per completing
      student and a mean cost of $18,400 per year of practice (expected 24.5 years in
      general practice), while dentistry also had a high training cost of $352,180 but
      an estimated costs of $11,140 per year of practice (based on an expected 31.6
      years in practice). Training costs are similar for dieticians and podiatrists,
      but because of differential workforce retention (mean 14.9 vs 31.5 years), the
      cost of training per year of clinical practice is twice as high for dieticians
      ($10,300 vs. $5200), only 8% lower than that for dentistry. Conclusions Return on
      investment in training across professions is highly variable, with expected time
      in the profession as important as the direct training cost. These results can
      indicate where increased retention and/or attracting trained professionals to
      return to practice should be the focus of any supply expansion versus increasing
      the student cohort.

PMID- 28429976
TI  - Reimbursement changes and drug switching: are severe patients more affected?
AB  - Objectives To examine the long-term effects of drug reimbursement adjustments on
      drug-switching decisions and to investigate whether patients with complicated or
      severe conditions are more affected. Methods A population-based, longitudinal
      study with a before-and-after design. Analysis of 141,703 patients with type 2
      diabetes covered by the universal health insurance program in Taiwan. Observation
      of five 6-month phases before and after a drug reimbursement adjustment
      implemented in October 2009. Drug switching was defined as a brand change within
      the same anatomical therapeutic chemical group between two consecutive physician
      visits. Generalized estimating equations were employed to control for the random
      subject effect. Results The drug-switching rates in the five phases were 10.85%
      and 13.71% before implementation and 31.53%, 28.29% and 15.61% after
      implementation. Results from the regression model revealed a higher likelihood of
      receiving switched drugs in phases 3, 4 and 5, with odds ratios of 3.16, 2.72 and
      1.44 (with 95% confidence interval 3.04-3.29, 2.61-2.84 and 1.38-1.51),
      respectively, compared with phase 1. Patients with complicated or severe
      conditions were more likely to have their drugs switched after the reimbursement
      adjustment. Conclusions The drug reimbursement adjustment under the health
      insurance program resulted in an increase in drug-switching decisions, and
      patients were not exempt from medication switching regardless of the
      complications or the severity level of their illness.

PMID- 28429977
TI  - Are some areas more equal than others? Socioeconomic inequality in potentially
      avoidable emergency hospital admissions within English local authority areas.
AB  - Objectives Reducing health inequalities is an explicit goal of England's health
      system. Our aim was to compare the performance of English local administrative
      areas in reducing socioeconomic inequality in emergency hospital admissions for
      ambulatory care sensitive chronic conditions. Methods We used local authority
      area as a stable proxy for health and long-term care administrative geography
      between 2004/5 and 2011/12. We linked inpatient hospital activity, deprivation,
      primary care, and population data to small area neighbourhoods (typical
      population 1500) within administrative areas (typical population 250,000). We
      measured absolute inequality gradients nationally and within each administrative
      area using neighbourhood-level linear models of the relationship between national
      deprivation and age-sex-adjusted emergency admission rates. We assessed local
      equity performance by comparing local inequality against national inequality to
      identify areas significantly more or less equal than expected; evaluated
      stability over time; and identified where equity performance was steadily
      improving or worsening. We then examined associations between change in
      socioeconomic inequalities and change in within-area deprivation
      (gentrification). Finally, we used administrative area-level random and fixed
      effects models to examine the contribution of primary care to inequalities in
      admissions. Results Data on 316 administrative areas were included in the
      analysis. Local inequalities were fairly stable between consecutive years, but 32
      areas (10%) showed steadily improving or worsening equity. In the 21 improving
      areas, the gap between most and least deprived fell by 3.9 admissions per 1000
      (six times the fall nationally) between 2004/5 and 2011/12, while in the 11 areas
      worsening, the gap widened by 2.4. There was no indication that measured
      improvements in local equity were an artefact of gentrification or that changes
      in primary care supply or quality contributed to changes in inequality.
      Conclusions Local equity performance in reducing inequality in emergency
      admissions varies both geographically and over time. Identifying this variation
      could provide insights into which local delivery strategies are most effective in
      reducing such inequalities.

PMID- 28429978
TI  - The cost-quality relationship in European hospitals: a systematic review.
AB  - Objective To determine the relationship between cost and quality in European
      hospitals. Methods Juran's cost-quality curve served as a theoretical framework,
      linked to basic efficiency concepts. Based on systematic database searches,
      citation searches and cross-referencing, we identify 1093 empirical studies.
      After exclusion of studies from outside Europe (699), non-hospital settings (10
      studies), lack of a cost parameter (194) or a quality parameter (27 studies), 22
      studies (28 analyses) were assessed for direction of association and
      methodological heterogeneity. Results There was evidence of positive, negative,
      two-directional and no association between cost and quality. We examined whether
      diagnosis, procedure, type of quality measure and specification of the
      econometric model could explain the inconsistent evidence, but no clear
      explanation is identified. Despite the significant policy relevance, evidence on
      the relationship between costs and quality is limited. The literature is
      characterized by substantial methodological heterogeneity and lack of explicit
      definitions of the chosen cost and quality parameters, the econometric model and
      the underlying hypothesis for the cost-quality relationship. Conclusion It has
      been more than 60 years since Juran introduced the idea of failure costs, which
      implied that the marginal costs of quality could be non-constant. It seems
      imperative to acknowledge this idea in future studies.

PMID- 28429979
TI  - From cutting costs to eliminating waste: reframing the challenge.

PMID- 28429980
TI  - Maimonides' middle path in the use of health care.

PMID- 28429981
TI  - Dying in hospital: socioeconomic inequality trends in England.
AB  - Objective To describe trends in socioeconomic inequality in the proportion of
      deaths occurring in hospital, during a period of sustained effort by the NHS in
      England to improve end of life care. Methods Whole-population, small area
      longitudinal study involving 5,260,871 patients of all ages who died in England
      from 2001/2002 to 2011/2012. Our primary measure of inequality was the slope
      index of inequality. This represents the estimated gap between the most and least
      deprived neighbourhood in England, allowing for the gradient in between.
      Neighbourhoods were geographic Lower Layer Super Output Areas containing about
      1500 people each. Results The overall proportion of patients dying in hospital
      decreased from 49.5% to 43.6% during the study period, after initially increasing
      to 52.0% in 2004/2005. There was substantial 'pro-rich' inequality, with an
      estimated difference of 5.95 percentage points in the proportion of people dying
      in hospital (confidence interval 5.26 to 6.63), comparing the most and least
      deprived neighbourhoods in 2011/2012. There was no significant reduction in this
      gap over time, either in absolute terms or relative to the mean, despite the
      overall reduction in the proportion of patients dying in hospital. Conclusions
      Efforts to reduce the proportion of patients dying in hospital in England have
      been successful overall but did not reduce inequality. Greater understanding of
      the reasons for such inequality is required before policy changes can be
      determined.

PMID- 28429982
TI  - A thing called Q.

PMID- 28429983
TI  - Children as agents of change in combatting antibiotic resistance.
AB  - Antibiotic resistance is a worldwide problem and changes are needed in the way
      antibiotics are used. The value of engaging children as key contributors in
      health care campaigns to increase the appropriate use of antibiotics has not been
      fully recognized. Little is known about how to design educational materials for
      children in order to enable them to be agents of change in their communities.
      Science education needs to improve the way it engages children so as to give them
      the tools needed to make responsible decisions on antibiotic use.

PMID- 28429984
TI  - Partnering to improve care: the case of the Veterans' Health Administration's
      Quality Enhancement Research Initiative.
AB  - Background Within many large health care organizations, researchers and
      operations partners (i.e., policymakers, managers, clinical leaders) join to
      conduct studies to improve the quality of patient care. Yet optimal approaches to
      conducting partnership research and evaluation are only beginning to be clearly
      defined. The Veterans' Health Administration (VA) Quality Enhancement Research
      Initiative (QUERI), funded by operations leaders and administered by the VA's
      research service, now has nearly two decades of experience in fostering research
      operations partnerships for improving quality of VA care. The work reported here
      is part of a national evaluation of QUERI. Because individuals in research and
      operations often have differing backgrounds and perspectives, we aim to identify
      the main sources of tension in research-operations partnerships and strategies
      for maximizing partnership success, through the eyes of QUERI participants.
      Methods We conducted semi-structured interviews with 116 researchers and
      operations partners chosen randomly from within pre-identified key participant
      groups. We conducted inductive qualitative analysis of verbatim interview
      transcripts, limited to the 89 interviews of individuals reporting at least some
      familiarity with QUERI. Results Tensions in research-operations partnerships were
      primarily related to diverging incentives and to differing values placed on
      scientific rigor or integrity versus quick timelines. To alleviate these
      tensions, operations' partners highlighted the importance of 'perspective-taking'
      (i.e., putting themselves into the shoes of the researchers) to ensure a mutually
      beneficial and attractive partnership, whereas researchers identified the
      importance of overcoming the need for recognition to be apportioned between
      either research or operations for achieved results. Both researchers and
      operations participants identified jointly designing each partnership from the
      beginning, minimizing research bureaucracy burdens, and prioritizing in-person
      communication and long-term relationships as key partnership building blocks.
      Conclusions QUERI research and operations participants had largely concordant
      views on partnership tensions and approaches for improving partnership success.
      The fact that only researchers mentioned moving beyond recognition for the
      results achieved and only operations staff mentioned the importance of
      'perspective-taking' suggests, however, that there may be unresolved tensions.
      These results suggest that researchers may benefit from better aligning of
      academic incentives with contributions to the health care organization and
      establishing formal recognition of operational impacts of research, while
      preserving some flexibility and independence of the research process.

PMID- 28429985
TI  - Attitude of US obstetricians and gynaecologists to global warming and medical
      waste.
AB  - Objectives Global warming (or climate change) is a major public health issue, and
      health services are one of the largest contributors to greenhouse gas emissions
      in high-income countries. Despite the scale of the health care sector's resource
      consumption, little is known about the attitude of physicians and their
      willingness to participate in efforts to reduce the environmental impact of
      health services. Methods A survey of 236 obstetricians and gynaecologists at the
      University of Pittsburgh Medical Center in Western Pennsylvania, USA. Survey
      responses were compared to Gallup poll data from the general population using a
      one-sample test of proportions, Fisher's exact tests, Chi-square test, and
      logistic regression. Results Physicians in obstetrics and gynaecology were more
      likely than the public (84% vs. 54%; p<0.001) to believe that global warming is
      occurring, that media portrayal of its seriousness is accurate, and that it is
      caused by human activities. Two-thirds of physicians felt the amount of surgical
      waste generated is excessive and increasing. The majority (95%) would support
      efforts to reduce waste, with 66% favouring the use of reusable surgical tools
      over disposable where clinically equivalent. Despite their preference for
      reusable surgical instruments, only 20% preferred the reusable devices available
      to them. Conclusions Health care providers engaging in sustainability efforts may
      encounter significant support from physicians and may benefit from including
      physician leaders in their efforts.

PMID- 28429986
TI  - Have individual medical savings accounts accumulated meaningful balances after 10
      years of enrolment? Empirical evidence from China.
AB  - Objectives To examine whether medical savings accounts in China have achieved the
      intended goal of promoting individual savings for medical care. Method
      Longitudinal data were obtained from one of the first Chinese cities that
      implemented medical savings accounts. The sample includes 246,681 enrolees with
      participation of at least 10 years by the end of 2010. We conducted descriptive
      analyses of medical savings account balances and a series of multivariate
      logistic analyses of risk factors for having low medical savings account
      accumulation. Results Medical savings account accumulation was low, with 41% of
      the enrolees having a balance below the average cost per outpatient visit, and
      the proportion increased to 54% and 58% when the deductible for inpatient care at
      secondary and tertiary hospitals was used as the threshold, respectively. Factors
      associated with having low medical savings account accumulation include female,
      old age, below high school education, retired and having a lower salary.
      Conclusion Medical savings accounts have not achieved the intended goal of
      encouraging personal savings for medical care. Given the low medical savings
      account accumulation, China's decision-makers need to adjust policies, especially
      during the current healthcare reform.

PMID- 28429987
TI  - Beyond integrated care.
AB  - Integrated care tops the health care agenda. But more integration alone will not
      remedy the crisis in health care, and there is a danger in the increasingly
      prevalent conceptualization of care integration as a goal in itself rather than
      as an instrument for improving performance. Operating integrated care systems,
      staffed by an overly specialized medical workforce, is unsustainable in terms of
      human and financial resources and is likely to produce little benefit for
      patients with multi-morbidity. An alternative approach involves health care
      leaders going beyond integrated care and nurturing transformative change from
      within the medical workforce instead. To be fit for purpose, the doctors must be
      encouraged and facilitated to customize their expertise to current and expected
      future burdens of disease. This would lead to more adaptive doctors who could
      actively support people in healing and managing their own health. Integrated care
      should be conceptualized as one possible lever for transformative change rather
      than its endpoint.

PMID- 28429988
TI  - Patient safety in nursing homes in Sweden: nurses' views on safety and their
      role.
AB  - Objective Knowledge about patient safety in nursing homes is limited. The aim of
      this study was to describe what patient safety means to nurses working in nursing
      homes for the elderly and how these nurses address patient safety. Method
      Qualitative study of semi-structured interviews with 15 nurses aged 27-62 years.
      Qualitative content analysis was applied. Results Nurses describe the meaning of
      patient safety in terms of proper care and treatment, and a sense of security.
      Based on nurses' description of patient safety, several factors were identified
      as prerequisites to achieve safe health care: competence; clear information
      transfer between health care organizations; continuity of care and appropriate
      environment. Barriers to patient safety were described as lack of sufficient
      resources; lack of communication and negative attitudes to incident reporting. To
      a great extent, nurses' work for patient safety consists of efforts to compensate
      for defects and ensure good health care in their daily work, since work with
      patient safety is not a management priority. Conclusion Patient safety needs to
      be clarified and prioritized in nursing homes, and there is a need to understand
      nurses' role among other care givers and the need for shared routines among care
      givers.

PMID- 28429989
TI  - Personalized medicine: what are the challenges for health services?
AB  - Genetics and genomics, together with other biomedical sciences and digital
      technologies, have a vital role to play in transforming health services to become
      systems that can work for health in the 21st century in ways that are affordable
      and that respond to individuals' requirement for more autonomy. Health services
      should embrace this agenda and implement changes in the organization of care.

PMID- 28429990
TI  - Medicaid waivers and negotiated federalism in the US: is there relevance to other
      federal systems?
AB  - Medicaid waivers have been a principal tool of innovation in health policy in the
      US since at least the mid 1970s. As Republicans seek to give the states more
      flexibility in their implementation and management of both Medicaid and the
      Affordable Care Act or its replacement, waiver authority is likely to be one of
      the key work arounds for avoiding political barriers in the US Senate. While
      block-granting Medicaid may require 60 senate votes, waiver authority already
      exists in both Medicaid law and the Affordable Care Act. Waivers also have great
      potential for application in other federal nations. Yet there is no theory to
      explain the way the application and review process evolves or the factors likely
      to shape the outcome. After a discussion of the theoretical underpinnings of what
      we call 'negotiated federalism', we apply it to examples of Medicaid waivers to
      see if the theory's key elements - politics, party congruence, leverage, credit
      taking and experience - offer a useful perspective on this federal-state
      interaction so important to health policy.

PMID- 28429991
TI  - Effects of medium-chain triglycerides on intestinal morphology and energy
      metabolism of intrauterine growth retarded weanling piglets.
AB  - It has been shown that there is a relationship between intrauterine growth
      retardation (IUGR) and postnatal intestinal damage involved in energy deficits.
      Therefore, the present study was conducted to investigate the effect of medium
      chain triglycerides (MCT) on the intestinal morphology, intestinal function and
      energy metabolism of piglets with IUGR. At weaning (21 +/- 1.1 d of age), 24 IUGR
      piglets and 24 normal birth weight (NBW) piglets were selected according to their
      birth weights (BW) (IUGR: 0.95 +/- 0.04 kg BW; NBW: 1.58 +/- 0.04 kg BW) and
      their weights at the time of weaning (IUGR: 5.26 +/- 0.15 kg BW; NBW: 6.98 +/-
      0.19 kg BW). The piglets were fed a diet of either long-chain triglycerides (LCT)
      (containing 5% LCT) or MCT (containing 1% LCT and 4% MCT) for 28 d. Then, the
      piglets' intestinal morphology, biochemical parameters and mRNA abundance related
      to intestinal damage and energy metabolism were determined. IUGR was found to
      impair intestinal morphology, with evidence of decreased villus height and
      increased crypt depth; however, these negative effects of IUGR were ameliorated
      by MCT treatment. IUGR piglets showed compromised intestinal digestion and
      absorption functions when compared with NBW piglets. However, feeding MCT
      increased the maltase activity in the jejunum and alleviated IUGR-induced
      reductions in plasma d-xylose concentrations and jejunal sucrase activity. IUGR
      decreased the efficiency of the piglets' intestinal energy metabolism; however,
      piglets fed an MCT diet exhibited increased adenosine triphosphate (ATP)
      concentrations and ATP synthase F1 complex beta polypeptide expression, as well
      as decreased adenosine monophosphate-activated kinase alpha 1 expression in the
      jejunum of piglets. In addition, up-regulation of the piglets' citrate synthase
      and succinate dehydrogenase levels was found to occur following MCT treatment at
      both the activity and the transcriptional levels of the jejunum. Therefore, it
      can be postulated that MCT treatment has beneficial effects in alleviating IUGR
      induced intestinal morphologic damage, which is associated with improved
      intestinal energy metabolism.

PMID- 28429992
TI  - Effect of replacing maize grain and soybean meal with a xylose-treated wheat
      grain on feed intake and performance of dairy cows.
AB  - This study evaluated wheat grain which was treated with xylose in aqueous Ca-Mg
      lignosulphonate solution at elevated temperatures (WeiPass(r)) in order to reduce
      ruminal degradation of starch and crude protein. The two tested isoenergetic and
      isonitrogenous diets contained on dry matter (DM) basis either 16% maize grain
      and 6.4% soybean meal (Diet CON) or 17.8% xylose-treated wheat and 4.6% soybean
      meal (Diet Wheat). Thirty-six German Holstein dairy cows were assigned to one of
      the two groups according to parity, body weight after calving, and milk yield
      during the previous lactation. Data collection started at 21 d before the
      expected calving date until 120 d in milk. The average of DM intake, energy
      corrected milk (ECM) yield, and milk fat and protein yields (all given as kg/d)
      were 18.9, 28.7, 1.25, and 1.02 for Diet CON and 19.3, 32.5, 1.36, and 1.11 for
      Diet Wheat, respectively. Only ECM and milk protein yields were greater (p <
      0.05) for cows receiving Diet Wheat. In conclusion, the xylose-treated wheat
      grain can replace maize grain and part of soybean meal in diets for lactating
      dairy cows and may be an alternative feedstuff depending on overall ration
      composition and availability and costs of grain sources.

PMID- 28429993
TI  - Interactive effects of protein and carbohydrates on production of microbial
      metabolites in the large intestine of growing pigs.
AB  - The study aimed at determining the effect of protein type and indigestible
      carbohydrates on the concentration of microbial metabolites in the large
      intestine of pigs. The experiment involved 36 pigs (15 kg initial body weight)
      divided into six groups, fed cereal-based diets with highly digestible casein
      (CAS) or potato protein concentrate (PPC) of lower ileal digestibility. Each diet
      was supplemented with cellulose, raw potato starch or pectin. After 2 weeks of
      feeding, pigs were sacrificed and samples of caecal and ascending, transverse and
      descending colon digesta were collected for analyses of microbial metabolites.
      PPC increased the concentration of ammonia, p-cresol, indole, n-butyrate,
      isovalerate and most of the amines in comparison with CAS. Pectin reduced the
      production of p-cresol, indole, phenylethylamine and isovalerate in the large
      intestine compared with potato starch. Starch and pectin increased mainly the
      concentration of n-butyrate and n-valerate in the colon compared to cellulose.
      Interaction affected mainly amines. Feeding PPC diet with potato starch
      considerably increased putrescine, cadaverine, tyramine and total amines
      concentrations compared with PPC diets with pectin and cellulose, whereas feeding
      CAS diet with starch reduced their concentrations. There was also a significant
      effect of interaction between diet and intestinal segment on microbial
      metabolites. In conclusion, PPC intensifies proteolysis in the large intestine
      and also n-butyrate production. Raw starch and pectin similarly increase n
      butyrate concentration but pectin inhibits proteolysis more efficiently than
      starch. The interactive effects of both factors indicate that pectin and
      cellulose may beneficially affect fermentative processes in case of greater
      protein flow to the large intestine.

PMID- 28429994
TI  - Ileal endogenous losses in pigs feeding a protein-free diet or diets with
      different contents of casein or crystalline amino acids.
AB  - The common usage of protein-free diets to estimate unspecific AA losses has been
      criticised as unphysiological and incorrect. Therefore, in this study different
      diets were tested for the determination of endogenous losses (EL) of amino acids
      (AA) and nitrogen (N) assuming a complete absorption in the small intestine.
      Seven cannulated gilts received a protein-free diet (Diet PF) or diets with 3%,
      6% or 10% crude protein (CP) from crystalline AA (Diets CA) or casein (Diets CAS)
      according to a 7 * 7 Latin square design. After 6 d adaptation to the diet, ileal
      digesta was collected for 24 h and thereafter analysed for AA, N and the
      digestibility markers Cr2O3 and acid insoluble ash (AIA). Generally, among all
      AA, the highest amounts of EL were found for Pro, Glu and Gly, and the smallest
      for Met. Different levels of CP in Diets CA and CAS had no effect on EL.
      Significant differences between treatments were observed only for the EL of Glu,
      Ile, Ser (higher in Diets CA and PF), Pro and Tyr (higher in Diet PF) (p < 0.05).
      There were no differences in determined EL using Cr2O3 or AIA as digestibility
      markers.

PMID- 28429995
TI  - New insights into the role of dietary spermine on inflammation, immune function
      and related-signalling molecules in the thymus and spleen of piglets.
AB  - This study aimed to determine the effects of dietary spermine supplementation on
      the inflammatory response and immune function of the thymus and spleen in
      piglets. Eighty suckling piglets were randomly assigned to receive adequate
      nutrients supplemented with spermine (0.4 mmol/kg body weight) or restricted
      nutrient intake supplemented with normal saline for 7 h or 3, 6 and 9 days in
      pairs. Regardless of treatment time, spermine supplementation decreased (p <
      0.05, compared with the controls) the following: (1) tumour necrosis factor alpha
      (TNF-alpha), interleukin (IL)-1beta, 2 and 6, and interferon (IFN)-gamma levels
      in serum; (2) gene expression of cluster of differentiation 8 and integrin beta-2
      in the thymus and spleen and the lymphocyte function-associated antigen 1 in the
      thymus; (3) mRNA levels of TNF-alpha, IL 1beta, 2, 6, and 12, IFN-gamma and
      inducible nitric oxide synthase in the thymus and spleen, as well as IL-8 in the
      spleen; and (4) eukaryotic IF4E-binding protein 1, Janus kinase 2, signal
      transducer and activator of transcription 3, and nuclear factor-kappa B P65 gene
      transcriptions in the thymus and spleen. By contrast, spermine supplementation
      increased (p < 0.05) the following: (1) immunoglobulin M, IL-10, and transforming
      growth factor beta1 gene expression, as well as (2) relative mRNA levels of
      mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase 1 in the
      thymus and spleen. These effects were also observed upon prolonged spermine
      administration (p < 0.05). In summary, dietary spermine supplementation can
      alleviate inflammatory response, enhance the immune function and regulate the
      gene expression of signalling molecules related to inflammation.

PMID- 28429996
TI  - Are Athletes' Doping-Related Attitudes Predicted by Their Perceptions of Coaches'
      Confrontation Efficacy?
AB  - BACKGROUND: The coaching process is complex and dynamic. Coaches are known to
      affect athlete attitudes indirectly, through athletes' perceptions and
      interpretations. This process has been verified with a variety of ethical
      behaviors. OBJECTIVES: The current study investigated the relationships between
      athletes' perceived doping confrontation efficacy of their coaches and athlete's
      anti-doping attitudes. METHODS: A sample of athletes (N = 96) completed a version
      of the Doping Confrontation Efficacy Scale that was modified to assess their
      perception of their coaches' anti-doping confrontation efficacy, and the PEAS
      (Performance Enhancing Attitude Scale), which assessed their performance
      enhancing attitudes. RESULTS: The results of a multiple linear regression model
      showed that perceived confrontation efficacy significantly predicted athletes'
      anti-doping attitudes. Specifically, the factor of efficacy with respect to
      intimacy was the sole significant predictor. CONCLUSIONS: These results show that
      a pattern of athletes' interpretation of coaches' values is related to their own
      attitudes, much like with cheating and sportsmanship. This finding is consistent
      with the conceptualization of confrontation in general independent of sport.

PMID- 28429997
TI  - Attitudes Toward Cognitive Enhancer Use Among New Zealand Tertiary Students.
AB  - BACKGROUND: Cognitive enhancement is the use of prescription stimulant medicines
      by healthy individuals for nonmedical use in academic settings. Commonly used
      cognitive enhancers (CEs) include methylphenidate, amphetamines, and modafinil.
      To understand the motivation to use CEs, it is important to look beyond
      prevalence and explore the extent to which attitudes, beliefs, and intentions
      predict the decision to use CEs. OBJECTIVE: The study aimed to investigate what
      factors explain the decision to use CEs among tertiary students in New Zealand,
      using the Theory of Planned Behaviour (TPB). METHODS: Students from the Schools
      of Pharmacy, Nursing, Medicine, Law, and Accounting at a university in New
      Zealand were invited to complete a paper-based questionnaire. The questionnaire
      elicited students' attitudes, subjective norms, and perceived control toward
      illicit use of CEs using TPB. An exploratory factor analysis was conducted.
      RESULTS: Response rate was 88.6% (442/499). Students who perceived CE use to be
      socially and ethically acceptable were more likely to use CEs (odds ratio, OR:
      1.56, 95% confidence interval, 95% CI: 1.153-2.105, p = 0.004). Students who were
      concerned about the health impact of CE use were less likely to use CEs (OR:
      0.54, 95% CI: 0.492-0.826, p = 0.001). Students who believed that CE use was
      approved were more likely to use them (OR: 1.648, CI: 1.193-2.278, p = 0.002).
      CONCLUSION: This research supports the notion that the decision to use CEs is not
      just an autonomous choice that occurs in isolation. Attitudes on the ethical and
      social acceptability of CE use were more likely to drive the decision to use CEs.
      The study provides the impetus for an integrative discussion by health care
      professionals and academics on the impact of attitudes, social norms, and
      advocates on the decision to use CEs.

PMID- 28429998
TI  - The Efficacy of a Pre-Workout Vegan Supplement on High-Intensity Cycling
      Performance in Healthy College-Aged Males.
AB  - There is a limited supply of sport nutrition supplements currently available for
      vegan or vegetarian athletes. In addition, the efficacy of a vegan or vegetarian
      pre-workout supplement that does not contain any processed ingredients or
      stimulants is currently unknown. The purpose of the current study was to examine
      the effects of an unprocessed vegan pre-workout supplement on high-intensity
      cycling performance. Participants completed three separate cycling trials
      following the consumption of a vegan pre-workout supplement, an isocaloric
      processed supplement, or a zero-calorie placebo supplement. Each supplement was
      consumed 30 minutes prior to each trial, and each cycling trial was separated by
      a minimum of 72 hours. Supplements were administered using a randomized, double
      blind cross-over design. Each cycling trial was performed at a workload equal to
      80% VO2peak until exhaustion. The average time in seconds (s) until exhaustion
      values for the vegan, isocaloric, and zero-calorie supplements were 482 +/- 163,
      480 +/- 157, and 496 +/- 238, respectively. Consumption of the vegan supplement
      did not significantly improve performance compared to an isocaloric and zero
      calorie supplement (F = 0.12, p =.89). The results of this study indicate that
      individuals who choose a vegan pre-workout supplement (over an isocaloric or zero
      calorie product) will not experience any acute decrements or ergogenic benefits
      in cycling performance. Although the present study does not support performance
      benefits of the tested vegan pre-workout supplement before cycling, additional
      research examining various exercise intensities and modalities is warranted.

PMID- 28429999
TI  - Beneficial Effects of Oral Supplementation With Ovoderm on Human Skin Physiology:
      Two Pilot Studies.
AB  - Collagens and hyaluronic acid have long been used in pharmaceuticals and food
      supplements for the improvement of skin elasticity and hydration. These compounds
      provide the building blocks of the skin. Ovoderm is an oral supplement obtained
      from eggshells that contains naturally occurring collagen and glycosaminoglycans,
      such as hyaluronic acid. We evaluated the efficacy of Ovoderm on skin biophysical
      parameters related to cutaneous aging such as elasticity, hydration, and
      pigmentation. Two pilot studies were run to assess the effect of daily oral
      supplementation with 300 mg Ovoderm on skin parameters. The first consisted of a
      self-assessment questionnaire intended to perform an assessment on skin, hair,
      and nail health after 50 days of treatment. The second measured the effect of 5
      week treatment on hydration by corneometry, on elasticity with the cutometer, and
      on pigmentation with the mexameter. In the pilot study 1, participants were
      predominantly satisfied with the effects obtained on general face (100%
      volunteers satisfied) and body (94% volunteers satisfied) skin condition and skin
      properties (100% volunteers satisfied with facial skin softness, 94% with facial
      skin hydration, and 89% with body skin hydration) and partly with effects on hair
      (67% volunteers satisfied) and nail (50% volunteers satisfied) condition. The
      study 2 revealed a statistically significant improvement in skin elasticity (12%
      increase, p =.0136), a tendency to reduce skin pigmentation (5% decrease), and no
      significant change in skin hydration. Our study reflects that oral
      supplementation with Ovoderm is efficacious to reduce the gradual loss of skin
      elasticity characteristic of aged skin, which helps to improve the appearance of
      the skin.

PMID- 28430001
TI  - Annexins in cell migration and adhesion.

PMID- 28430000
TI  - Neuroprotective and regenerative roles of intranasal Wnt-3a administration after
      focal ischemic stroke in mice.
AB  - Wnt signaling is a conserved pathway involved in expansion of neural progenitors
      and lineage specification during development. However, the role of Wnt signaling
      in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt
      3a would play an important role for neurogenesis and brain repair. Adult male
      mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex.
      Mice that received Wnt-3a (2 ug/kg/day, 1 h after stroke and once a day for the
      next 2 days, intranasal delivery) had reduced infarct volume compared to stroke
      controls. Wnt-3a intranasal treatment of seven days upregulated the expression of
      brain-derived growth factor (BDNF), increased the proliferation and migration of
      neuroblasts from the subventricular zone (SVZ), resulting in increased numbers of
      newly formed neurons and endothelial cells in the peri-infarct zone. Both the
      molecular and cellular effects of Wnt-3a were blocked by the Wnt specific
      inhibitors XAV-939 or Dkk-1. In functional assays, Wnt-3a treatment enhanced the
      local cerebral blood flow (LCBF) in the peri-infarct, as well as improved
      sensorimotor functions in a battery of behavioral tests. Together, our data
      demonstrates that the Wnt-3a signaling can act as a dual neuroprotective and
      regenerative factor for the treatment of ischemic stroke.

PMID- 28430002
TI  - Audit of submissions: July 2015-June 2016.

PMID- 28430003
TI  - Screening.

PMID- 28430004
TI  - A strategy for L-isoleucine dioxygenase screening and 4-hydroxyisoleucine
      production by resting cells.
AB  - L-Isoleucine dioxygenase (IDO) specifically converts L-isoleucine(L-Ile) to 4
      hydroxyisoleucine(4-HIL). To obtain IDO with improved activity, a strategy was
      developed that is dependent on the restoration of succinate-minus E. coli cell
      growth by the coupling of L-Ile hydroxylation and the oxidation of alpha
      ketoglutarate(alpha-KGA) to succinate. Five mutants were obtained with this
      strategy, and the characteristics of IDOM3, which exhibited the highest activity,
      were studied. The catalytic efficiency, thermal stability and catalytic rate of
      IDOM3 were significantly improved compared with those of wild-type IDO. Moreover,
      an efficient method for the biotransformation of 4-HIL by resting cells
      expressing IDOM3 was developed, with which 151.9 mmol of 4-HIL/L (22.4 g/L) was
      synthesized in 12 h while the substrates seldom exhibited additional consumption.

PMID- 28430005
TI  - Issues in current microRNA target identification methods.
AB  - microRNAs are currently believed to control a large diversity of physiologic
      processes, through the collective repression of thousands of target genes. Both
      experimental and computational analyses indeed suggest that each microRNA
      regulates tens or hundreds of genes. But some observations suggest that the
      phenotypic consequences of many published miRNA/mRNA interactions are dubious.
      For example, the reported amplitude of miRNA-guided repression is very small,
      while biologic processes tend to be robust to small changes in gene expression.
      We recently showed, on one particular miRNA, that for most predicted targets,
      miRNA-guided repression is even smaller than inter-individual variability among
      wild-type specimens. We also put forward several sources of computational false
      positives. These issues are generally neglected by the scientific community,
      probably resulting in the frequent publication of irreproducible or
      misinterpreted results regarding microRNA function. We propose novel types of
      analyses, easily accessible to the community, that could help improve microRNA
      target identification.

PMID- 28430006
TI  - Evolutionary changes in lamin expression in the vertebrate lineage.
AB  - The nuclear lamina is involved in fundamental nuclear functions and provides
      mechanical stability to the nucleus. Lamin filaments form a meshwork closely
      apposed to the inner nuclear membrane and a small fraction of lamins exist in the
      nuclear interior. Mutations in lamin genes cause severe hereditary diseases, the
      laminopathies. During vertebrate evolution the lamin protein family has expanded.
      While most vertebrate genomes contain 4 lamin genes, encoding the lamins A, B1,
      B2, and LIII, the majority of non-vertebrate genomes harbor only a single lamin
      gene. We have collected lamin gene and cDNA sequence information for
      representatives of the major vertebrate lineages. With the help of RNA-seq data
      we have determined relative lamin expression levels for representative tissues
      for species of 9 different gnathostome lineages. Here we report that the level of
      lamin A expression is low in cartilaginous fishes and ancient fishes and
      increases toward the mammals. Lamin B1 expression shows an inverse tendency to
      that of lamin A. Possible implications for the change in the lamin A to B ratio
      is discussed in the light of its role in nuclear mechanics.

PMID- 28430007
TI  - The Feasibility and Impact of Prospective Medication Review in the Emergency
      Department.
AB  - OBJECTIVE: We evaluated the feasibility and impact of prospective medication
      review (PMR) in the emergency department (ED). METHODS: This was a retrospective
      cohort study of all nonadmitted ED patients who were prescribed medication orders
      by ED clinicians from September 2014 to September 2015 to determine the time
      intervals utilized during each step of the medication use process and quantify
      the number of interventions conducted by the pharmacist and cost avoidance
      accrued from the interventions. RESULTS: A total of 834 medication orders were
      included for evaluation. The median time for order verification, order
      verification to dispense, and dispense to administration were 3 minutes
      (interquartile range [IQR] = 1-7 minutes), 20 minutes (IQR = 7-45 minutes), and
      10 minutes (IQR = 6-16 minutes). The median time interval for order verification
      was longer during the overnight pharmacy shift (median = 5 minutes, IQR = 2-9
      minutes) compared to the day and evening shifts (median = 3 minutes, IQR = 1-6
      minutes). A total of 563 interventions were recommended by the pharmacists and
      accepted by ED clinicians. These interventions equated to US$47 585 worth of cost
      avoidance. CONCLUSION: The PMR is a feasible process that resulted in safe and
      effective use of medications without causing delays to patient care.

PMID- 28430008
TI  - [Behaviour problems of children with Down syndrome in preschool-age - Results
      from the Heidelberg Down syndrome study].
AB  - Aims: We report on the frequency and the correlations of behaviour problems among
      children with Down syndrome in preschool-age. Method: As part of a longitudinal
      study 48 mothers of children with Down syndrome completed the German version of
      the "Strengths and Difficulties Questionnaire" (SDQ-D) and the Parenting Stress
      Inventory (PSI). The mothers were asked to fill out the questionnaires when the
      children had a mean age of five years. The results were compared to norms from
      children with typical development. Results: Thirty per cent of the children with
      Down syndrome were rated as abnormal. Specifically, mean scores indicating
      problems with children of the same age and hyperactivity were elevated. A
      regression analysis predicting the total problem score of the SDQ-D revealed
      maternal educational level, optimistic attitude, and subjective parental stress
      at the age of one year and the degree of behavioural abnormalities at the age of
      three years as significant influential factors. Conclusion: Early intervention
      for Down syndrome children should include supporting parenting competence and
      coping skills in order to prevent behaviour problems.

PMID- 28430009
TI  - Evaluating Questionnaires Used to Assess Self-Reported Physical Activity and
      Psychosocial Outcomes Among Survivors of Adolescent and Young Adult Cancer: A
      Cognitive Interview Study.
AB  - Physical activity is increasingly being studied as a way to improve psychosocial
      outcomes (e.g., quality of life, self-efficacy, physical self-perceptions, self
      esteem, body image, posttraumatic growth) among survivors of adolescent and young
      adult (AYA) cancer. Assessing levels of and associations between self-reported
      physical activity and psychosocial outcomes requires clear, appropriate, and
      relevant questionnaires. To explore how survivors of AYA cancer interpreted and
      responded to the following eight published questionnaires: Leisure Time Exercise
      Questionnaire, Exercise Self-Efficacy Scale, Physical Self-Description
      Questionnaire, Rosenberg Global Self-Esteem Scale, Multidimensional Body-Self
      Relations Questionnaire, Posttraumatic Growth Inventory, Functional Assessment of
      Cancer Therapy-General (FACT-G), RAND 36-Item Health Survey 1.0 (RAND-36),
      cognitive interviews were conducted with three men and four women age 18-36 years
      who were diagnosed with cancer at age 16-35 years. Initially, the first seven
      questionnaires listed above were assessed. Summaries of the interviews were
      prepared and compared across participants. Potential concerns were identified
      with the FACT-G; thus, a second interview was conducted with participants to
      explore the clarity, appropriateness, and relevance of the RAND-36. Concerns
      identified for the FACT-G related mostly to the lack of relevance of items
      pertaining to cancer-specific aspects of quality of life given that participants
      were posttreatment. No or few concerns related to comprehension and/or
      structure/logic were identified for the other questionnaires. In general, the
      questionnaires assessed were clear, appropriate, and relevant. Participants'
      feedback suggested they could be used to assess self-reported physical activity
      and varied psychosocial outcomes in studies with survivors of AYA cancer, either
      with or without slight modifications.

PMID- 28430010
TI  - Prolonged injectable formulation of Nafarelin using in situ gel combination
      delivery system.
AB  - The principal purpose of the present study was to prepare and characterize a
      complex drug delivery system consisting of Nafarelin-poly (3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) nanoparticles (NPs) in combination with sodium
      alginate/poloxamer 407 in situ gel. Nafarelin-loaded PHBV NPs were prepared via
      double emulsion solvent evaporation technique. Box-Behnken Response Surface
      Methodology was utilized to optimize NPs. Mean particle size, polydispersity
      index (PDI), entrapment efficiency (EE), and drug loading (DL) of the optimized
      NPs were measured. Incorporation of Nafarelin within NPs was proven by
      differential scanning calorimetry (DSC). The combination delivery system (CDS)
      was prepared by adding Nafarelin-loaded PHBV NPs to sodium alginate/poloxamer 407
      solution followed by physical mixing. Morphological properties of Nafarelin
      loaded PHBV NPs and CDS were evaluated by SEM. Rheological properties were
      employed to investigate the effects of alginate concentration on sol-gel
      transition temperature. The release profile of Nafarelin from both PHBV NPs and
      CDS were individually assessed. The cumulative release percentage from CDS was
      significantly lower than Nafarelin released from PHBV NPs. Based on the favorable
      results in this study, the CDS consisting of sodium alginate/poloxamer 407 loaded
      with PHBV NPs could be a promising candidate for designing a long-lasting
      formulation of Nafarelin.

PMID- 28430011
TI  - Demographics of hip dysplasia in the Maine Coon cat.
AB  - Objectives The aim of this study was to report the demographics of feline hip
      dysplasia (FHD) in the Maine Coon cat. Methods The complete hip dysplasia
      registry (public and private) collected by the Orthopedic Foundation for Animals
      through April 2015 was accessed. There were 2732 unique cats; 2708 (99.1%) were
      Maine Coons, and only these were studied. Variables analyzed were sex,
      month/season of birth and hip dysplasia score. Two groups were created: those
      with and without FHD. P <0.05 was considered statistically significant. Results
      The youngest cat with FHD was 4 months of age. The majority of the radiographs
      (2604/2708 [96.2%]) were performed between 4 and 60 months of age. Non-borderline
      scores for these 2604 cats were available in 2548, and were the data used for
      this study. The overall prevalence of FHD was 24.9% (635/2548), and was slightly
      higher in males (279/1023 [27.3%]) than females (356/1525 [23.3%]) ( P = 0.025).
      Those with more severe dysplasia were older. The percentage of bilateral FHD was
      56%, and bilateral cases had more severe dysplasia than unilateral cases but with
      no age difference. Month/season of birth or geographic region of origin did not
      influence the prevalence of FHD. Conclusions and relevance This is the largest
      demographic study of FHD in the Maine Coon cat. The overall prevalence in the
      Orthopedic Foundation for Animals registry was 24.9%, and slightly higher in
      males (27.3%) than females (23.3%). Dysplasia was more severe in bilateral than
      unilateral cases and with increasing age. Caution should be used when
      extrapolating these findings to other feline breeds or other groups of Maine Coon
      cats. Further studies need to be performed among other breeds and geographic
      locations to better understand the demographics of feline hip dysplasia.

PMID- 28430012
TI  - ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular
      endothelial cells.
AB  - The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases
      in some disorders such as vascular dementia, Alzheimer's disease, and multiple
      sclerosis. We previously reported that in Alzheimer's disease patients, a high
      level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood
      brain barrier tight junction protein, and facilitated the infiltration of
      peripheral monocytes across the blood-brain barrier. However, the molecular
      mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear. Herein,
      we found that the erythroblast transformation-specific (ETS) transcription factor
      ERG cooperated with the proto-oncogene protein c-MYC in regulation of ZO-1
      transcription in brain microvascular endothelial cells (BMECs). The ERG
      expression was suppressed by miR-96 which was increased by GM-CSF through the
      phosphoinositide-3 kinase (PI3K)/Akt pathway. Inhibition of miR-96 prevented ZO-1
      down-regulation induced by GM-CSF both in vitro and in vivo. Our results revealed
      the mechanism of ZO-1 expression reduced by GM-CSF, and provided a potential
      target, miR-96, which could block ZO-1 down-regulation caused by GM-CSF in BMECs.

PMID- 28430013
TI  - Barriers to Access to Sterile Syringes as Perceived by Pharmacists and Injecting
      Drug Users: Implications for Harm Reduction in Lebanon.
AB  - BACKGROUND: Access to sterile syringes to injecting drug users (IDU) reduces
      sharing behavior and prevents the transmission of HIV. OBJECTIVES: To describe
      the barriers to access to sterile syringes for IDUs in Lebanon from the
      perspectives of pharmacists and IDUs. METHODS: in this qualitative study
      conducted in Lebanon, data were collected from 72 syringe purchase tests at
      pharmacies, 64 interviewees with pharmacists and 2 focus groups with injecting
      drug users. Two independent researchers analyzed the verbatim transcripts.
      RESULTS: Results revealed that pharmacists often deny access to sterile syringes
      to IDUs who are frequently stigmatized and intimidated at pharmacies. While no
      large gender differences in pharmacists' attitudes and practices were observed,
      inequalities in syringe access were noticed with men IDUs more often denied
      purchase. Pharmacists had several barriers to sell syringes to IDUs including
      fear of disease spread, increased drug use, inappropriately discarded syringes,
      staff and customer safety, and business concerns. IDUs had several challenges to
      purchase syringes including stigmatization, intimidation, physical harassment,
      concern to reveal identity, fear of arrest and syringe price abuse. CONCLUSIONS:
      Identifying the barriers to and facilitators of access to sterile syringes to
      IDUs is important to guide the development of efficient policies. Findings
      implicate the importance of empowering IDUs to purchase syringes at pharmacies
      through reducing the negative attitude towards IDUs and strengthening
      pharmacists' role in the promotion of health of IDUs. Findings also suggest that
      the habit of syringe sharing would decrease if the legal and cultural barriers to
      access are reduced.

PMID- 28430014
TI  - Pediatric Oral Motor Feeding Assessments: A Systematic Review.
AB  - AIM: To describe the clinical properties and psychometric soundness of pediatric
      oral motor feeding assessments. METHODS: A systematic search was conducted using
      Medline, CINAHL, EMBASE, PsycInfo, and HAPI databases. Assessments were analyzed
      for their clinical and psychometric characteristics. RESULTS: 12 assessment tools
      were identified to meet the inclusion/exclusion criteria. Clinical properties
      varied from assessments evaluating oral-motor deficits, screening to identify
      feeding problems, and monitoring feeding progress. Most assessments were designed
      for children with developmental disabilities or cerebral palsy. Eleven
      assessments had psychometric evidence, of these nine had reliability and validity
      testing (Ability for Basic Feeding and Swallowing Scale for Children, Behavioral
      Assessment Scale of Oral Functions in Feeding, Dysphagia Disorder Survey,
      Functional Feeding Assessment-modified, Gisel Video Assessment, Montreal
      Children's Hospital Feeding Scale, Oral Motor Assessment Scale, Schedule for Oral
      Motor Assessment, and Screening Tool of Feeding Problems Applied to Children).
      The Brief Assessment of Motor Function-Oral Motor Deglutition and the Pediatric
      Assessment Scale for Severe Feeding Problems had reliability testing only. The
      Slurp Test was not tested for any psychometric properties. Overall, psychometric
      evidence was inconsistent and inadequate for the evaluative tools.

PMID- 28430015
TI  - A Randomized Controlled Trial of a Mindfulness and Acceptance Group Therapy for
      Residential Substance Use Patients.
AB  - BACKGROUND: Substance use disorders are understood as a chronically relapsing
      condition that is difficult to treat. However, in recent years there have been
      promising developments in the treatment of substance use disorders, specifically
      with interventions based on mindfulness and acceptance and commitment therapy.
      Little research has examined whether these types of interventions may positively
      impact residential substance use treatment outcomes. OBJECTIVES: Thus, in the
      current study we developed and examined, in a randomized controlled trial, a 4
      week, eight-session, adjunctive mindfulness and acceptance group therapy for
      patients in residential substance use treatment. Our primary outcomes were
      substance use cravings, psychological flexibility, and dispositional mindfulness
      at treatment discharge. METHODS: Patients (N = 117) from a private residential
      substance use facility were randomized to receive the adjunctive mindfulness and
      acceptance group or treatment-as-usual. Patients were assessed at treatment
      intake and at discharge from a 28-30-day residential program. RESULTS: Although
      treatment groups did not statistically differ at discharge on any primary
      outcome, small effect sizes favored the mindfulness and acceptance group on
      cravings and psychological flexibility. Conclusions/Importance: Continued
      research is needed to determine whether the addition of mindfulness and
      acceptance-based interventions improve outcomes long term following residential
      substance use treatment.

PMID- 28430016
TI  - The Use of Intravenous Lidocaine for the Management of Acute Pain Secondary to
      Traumatic Ankle Injury: A Case Report.
AB  - Sports-related injuries are a frequent cause of visits to the emergency
      department (ED) across the United States. A majority of these injuries affect the
      lower extremities with the ankle as the most frequently reported site. Most
      sports-related injuries are not severe enough to require inpatient
      hospitalization; however, they often lead to acute distress and pain which
      require prompt treatment with analgesics. Approximately 22% of patients who
      presented to the ED required pharmacotherapy for acute pain management. Opioids
      have been traditionally used for the management of severe acute pain in the ED;
      however, there are growing concerns for opioid overuse and misuse. As a result,
      there is growing controversy regarding the appropriate selection of analgesic
      agents, optimal dosing, and need for outpatient therapy which has contributed to
      changes in prescribing patterns of opioids in the ED. Lidocaine, a class 1b
      antiarrhythmic, has been utilized as an analgesic agent. Its use has been
      documented for the management of intractable chronic pain caused by cancer,
      stroke, neuropathies, or nephrolithiasis. However, literature describing the use
      of intravenous lidocaine for the management of acute pain secondary to trauma is
      limited to a single case series. This case report describes the use of
      intravenous lidocaine in a 17-year-old male who presented to the ED in acute
      distress secondary to ankle dislocation and fracture. This report serves to
      describe additional clinical experience with intravenous lidocaine for the
      management of acute pain secondary to ankle fracture in the emergency department.

PMID- 28430017
TI  - Two NRAMP6 Isoforms Function as Iron and Manganese Transporters and Contribute to
      Disease Resistance in Rice.
AB  - Metal ions are essential elements for all living organisms. However, metals can
      be toxic when present in excess. In plants, metal homeostasis is partly achieved
      through the function of metal transporters, including the diverse natural
      resistance-associated macrophage proteins (NRAMP). Among them, the OsNramp6 gene
      encodes a previously uncharacterized member of the rice NRAMP family that
      undergoes alternative splicing to produce different NRAMP6 proteins. In this
      work, we determined the metal transport activity and biological role of the full
      length and the shortest NRAMP6 proteins (l-NRAMP6 and s-NRAMP6, respectively).
      Both l-NRAMP6 and s-NRAMP6 are plasma membrane-localized proteins that function
      as iron and manganese transporters. The expression of l-Nramp6 and s-Nramp6 is
      regulated during infection with the fungal pathogen Magnaporthe oryzae, albeit
      with different kinetics. Rice plants grown under high iron supply show stronger
      induction of rice defense genes and enhanced resistance to M. oryzae infection.
      Also, loss of function of OsNramp6 results in enhanced resistance to M. oryzae,
      supporting the idea that OsNramp6 negatively regulates rice immunity.
      Furthermore, nramp6 plants showed reduced biomass, pointing to a role of OsNramp6
      in plant growth. A better understanding of OsNramp6-mediated mechanisms
      underlying disease resistance in rice will help in developing appropriate
      strategies for crop protection.

PMID- 28430018
TI  - Characterization of Canna yellow mottle virus in a New Host, Alpinia purpurata,
      in Hawaii.
AB  - Canna yellow mottle virus (CaYMV) is an important badnavirus infecting Canna spp.
      worldwide. This is the first report of CaYMV in flowering ginger (Alpinia
      purpurata) in Hawaii, where it is associated with yellow mottling and necrosis of
      leaves, vein streaking, and stunted plants. We have sequenced CaYMV in A.
      purpurata (CaYMV-Ap) using a combination of next-generation sequencing and
      traditional Sanger sequencing techniques. The complete genome of CaYMV-Ap was
      7,120 bp with an organization typical of other Badnavirus species. Our results
      indicated that CaYMV-Ap was present in the episomal form in infected flowering
      ginger. We determined that this virus disease is prevalent in Hawaii and could
      potentially have significant economic impact on the marketing of A. purpurata as
      cut flowers. There is a potential concern that the host range of CaYMV-Ap may
      expand to include other important tropical plants.

PMID- 28430019
TI  - Characterization of Rph24: A Gene Conferring Adult Plant Resistance to Puccinia
      hordei in Barley.
AB  - We identified Rph24 as a locus in barley (Hordeum vulgare L.) controlling adult
      plant resistance (APR) to leaf rust, caused by Puccinia hordei. The locus was
      previously reported as a quantitative trait locus in barley line ND24260-1 and
      named qRphND. We crossed ND24260-1 to the leaf-rust-susceptible standard Gus and
      determined inheritance patterns in the progeny. For the comparative marker
      frequency analysis (MFA), resistant and susceptible tails of the F2 were
      genotyped with Diversity Arrays Technology genotyping-by-sequencing (DArT-Seq)
      markers. The Rph24 locus was positioned at 55.5 centimorgans on chromosome 6H on
      the DArT-Seq consensus map. Evaluation of F2:3 families confirmed that a single
      locus from ND24260-1 conferred partial resistance. The haploblock strongly
      associated with the Rph24 locus was used to estimate the allele frequency in a
      collection of 282 international barley cultivars. Rph24 was frequently paired
      with APR locus Rph20 in cultivars displaying high levels of APR to leaf rust. The
      markers identified in this study for Rph24 should be useful for marker-assisted
      selection.

PMID- 28430020
TI  - Health Differences Among Lesbian, Gay, and Transgender Veterans by Rural/Small
      Town and Suburban/Urban Setting.
AB  - PURPOSE: We explored the relationship between geographic location and health
      indicators for lesbian, gay, and transgender veterans. METHODS: We solicited
      participation in an online survey through national and city LGBT organizations
      and personal contacts to examine differences in depression, anxiety, alcohol and
      tobacco use, and body mass index among lesbian, gay, and transgender veterans (n
      = 252) in suburban/urban and rural/small town locations. Bisexual participants
      were too few to include in the analyses. RESULTS: As expected, rural/small town
      lesbian, gay, and transgender veterans spent more time traveling to their primary
      care provider. Travel time was also positively related to depressive and anxiety
      symptoms. However, only suburban/urban and rural/small town gay men differed in
      measures of depression and anxiety and tobacco use. That is, rural/small town gay
      men reported greater depressive and anxiety symptoms and greater tobacco use than
      their suburban/urban counterparts. Consistent with this finding, rural/small town
      gay men reported less community-related identity than suburban/urban men.
      Suburban/urban lesbian women showed a nonsignificant trend for community identity
      compared with rural/small town women. CONCLUSION: Similar to civilian studies,
      suburban/urban and rural/small town lesbian, gay, and transgender veterans
      evidenced few health differences, with the exception of suburban/urban gay men.
      Although rural/small town gay male veterans evidenced more depression and anxiety
      and less community identity than suburban/urban men, social networks likely
      differ for lesbian, gay, and transgender subgroups. Lesbian, gay, and transgender
      veterans may also differ from their civilian counterparts in ways that we do not
      yet understand.

PMID- 28430021
TI  - Family Perspectives on Telemedicine for Pediatric Subspecialty Care.
AB  - BACKGROUND: Children often have difficulty accessing subspecialty care, and
      telemedicine may improve access to subspecialty care, but information is lacking
      on how best to implement telemedicine programs to maximize acceptance and,
      ultimately, maximize impact for patients and their families. METHODS AND
      MATERIALS: To understand how subspecialty telemedicine is perceived and to
      identify design elements with the potential to improve telemedicine uptake and
      impact, we conducted and analyzed semi-structured interviews with 21 informants,
      including parents and caregivers of children with subspecialty care needs and
      adolescent and young adult patients with subspecialty care needs. RESULTS:
      Although informants saw the potential value of using telemedicine to replace in
      person subspecialty visits, they were more enthusiastic about using telemedicine
      to complement rather than replace in-person visits. For example, they described
      the potential to use telemedicine to facilitate previsit triage encounters to
      assess whether the patient was being scheduled with the correct subspecialist and
      with the appropriate level of urgency. They also felt that telemedicine would be
      useful for communication with subspecialists after scheduled in-person visits for
      follow-up questions, care coordination, and to discuss changes in health status.
      Informants felt that it was important for telemedicine programs to have
      transparent and reliable scheduling, same-day scheduling options, continuity of
      care with trusted providers, clear guidelines on when to use telemedicine, and
      preservation of parent choice regarding method of care delivery. CONCLUSIONS:
      Parents and patients articulated preferences regarding pediatric subspecialty
      telemedicine in this qualitative, hypothesis-generating study. Understanding and
      responding to patient and caregiver perceptions and preferences will be crucial
      to ensure that telemedicine drives true innovation in care delivery rather than
      simply recapitulating prior models of care.

PMID- 28430022
TI  - Safety by design of printed multilayer materials intended for food packaging.
AB  - Printing inks are commonly used in multilayer plastics materials used for food
      packaging, and compounds present in inks can migrate to the food either by
      diffusion through the multilayers or because of set-off phenomena. To avoid this
      problem, the right design of the packaging is crucial. This paper studies the
      safety by design of multilayer materials. First, the migration from four
      different multilayers manufactured using polyethylene terephthalate (PET),
      aluminium (Al) and polyethylene (PE) was determined. The structural differences
      among materials such as the presence of inks or lacquer coatings as well as the
      differences in layers position allowed the study of a safety-by-design approach.
      Sixty-nine different compounds were detected and identified; 49 of them were not
      included in the positive list of Regulation EU/10/2011 or in Swiss legislation
      and 15 belong to Cramer class III, which means that they have a theoretical high
      toxicity. Some of the compounds related to ink composition were pyrene, a
      compound commercially used to make dyes and dye precursors and the antioxidant
      Irganox 1300. The application of external lacquers decreased the concentration of
      some migrants but also brought the potential for new migrants coming from its
      composition. A final risk assessment of the material allowed evaluating food
      safety for different food simulants and confirm it.

PMID- 28430024
TI  - Cacao Phylloplane: The First Battlefield against Moniliophthora perniciosa, Which
      Causes Witches' Broom Disease.
AB  - The phylloplane is the first contact surface between Theobroma cacao and the
      fungus Moniliophthora perniciosa, which causes witches' broom disease (WBD). We
      evaluated the index of short glandular trichomes (SGT) in the cacao phylloplane
      and the effect of irrigation on the disease index of cacao genotypes with or
      without resistance to WBD, and identified proteins present in the phylloplane.
      The resistant genotype CCN51 and susceptible Catongo presented a mean index of
      1,600 and 700 SGT cm-2, respectively. The disease index in plants under drip
      irrigation was reduced by approximately 30% compared with plants under sprinkler
      irrigation prior to inoculation. Leaf water wash (LWW) of the cacao inhibited the
      germination of spores by up to 98%. Proteins from the LWW of CCN51 were analyzed
      by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis
      followed by tandem mass spectrometry. The gel showed 71 spots and identified a
      total of 42 proteins (28 from the plant and 14 from bacteria). Proteins related
      to defense and synthesis of defense metabolites and involved in nucleic acid
      metabolism were identified. The results support the hypothesis that the proteins
      and water-soluble compounds secreted to the cacao phylloplane participate in the
      defense against pathogens. They also suggest that SGT can contribute to the
      resistance of cacao.

PMID- 28430023
TI  - Harnessing Effector-Triggered Immunity for Durable Disease Resistance.
AB  - Genetic control of plant diseases has traditionally included the deployment of
      single immune receptors with nucleotide-binding leucine-rich repeat (NLR) domain
      architecture. These NLRs recognize corresponding pathogen effector proteins
      inside plant cells, resulting in effector-triggered immunity (ETI). Although ETI
      triggers robust resistance, deployment of single NLRs can be rapidly overcome by
      pathogen populations within a single or a few growing seasons. In order to
      generate more durable disease resistance against devastating plant pathogens, a
      multitiered strategy that incorporates stacked NLRs combined with other sources
      of disease resistance is necessary. New genetic and genomic technologies have
      enabled advancements in identifying conserved pathogen effectors, isolating NLR
      repertoires from diverse plants, and editing plant genomes to enhance resistance.
      Significant advancements have also been made in understanding plant immune
      perception at the receptor level, which has promise for engineering new sources
      of resistance. Here, we discuss how to utilize recent scientific advancements in
      a multilayered strategy for developing more durable disease resistance.

PMID- 28430025
TI  - Synthesis of dopamine in E. coli using plasmid-based expression system and its
      marked effect on host growth profiles.
AB  - L-Dopa and dopamine are important pathway intermediates toward the synthesis of
      catecholamine such as epinephrine and norepinephrine from amino acid L-tyrosine.
      Dopamine, secreted from dopaminergic nerve cells, serves as an important
      neurotransmitter. We report the synthesis of dopamine by extending the aromatic
      amino acid pathway of Escherichia coli DH5alpha by the expression of 4
      hydroxyphenylacetate-3-hydrolase (HpaBC) from E. coli and an engineered dopa
      decarboxylase (DDC) from pig kidney cell. The activity of HpaBC and DDC require
      200 uM iron supplementation and 50 uM vitamin B6, respectively as additives to
      the growth media. The maximum concentration of L-dopa and dopamine obtained from
      the broth was around 26 and 27 mg/L after 24 hr of separate shake flask studies.
      We observed that in the presence of dopamine synthesized in vivo host growth was
      remarkably enhanced. These observations lead us to an interesting finding about
      the role of these catecholamines on bacterial growth. It is clear that synthesis
      of dopamine in vivo actually promotes growth much efficiently as compared to when
      dopamine is added to the system from outside. From HPLC and GC-MS data it was
      further observed that L-dopa was stable within the observable time of experiments
      whereas dopamine actually was subjected to degradation via oxidation and host
      consumption.

PMID- 28430026
TI  - Expanding the Types of Clients Receiving Sex Therapy and Sexual Health Services.
AB  - The provision of sex therapy primarily occurs for middle-class couples by middle
      class clinicians. This conceptual/clinical article advocates for sex therapy
      approaches that better meet the needs of individuals and couples within a broader
      socioeconomic range, and includes two case studies as examples. Every couple,
      regardless of socioeconomic status, deserves first-class sex therapy that helps
      establish a satisfying, secure, and sexual relationship from an empathic,
      respectful clinician who remains sensitive to specific vulnerabilities and
      challenges related to economic and social class factors.

PMID- 28430027
TI  - A comparison of the performance of 2.5 to 3.5-year-old children without
      disabilities using animated and cursor-based scanning in a contextual scene.
AB  - Although recent evidence suggests learning demands for children can be reduced by
      organizing augmentative and alternative communication (AAC) displays in
      contextual scenes, there is little evidence on how such scenes could be made
      accessible for children who cannot use direct selection. Using a line drawn scene
      of a living room, a traditional traveling cursor (a green outline of objects
      within the scene) was compared with sequential animation-logically matching the
      function of items in the scene (e.g., hands of a clock moving, a lamp turning on
      and off, etc.). After three learning sessions, only the matched function
      animation condition revealed a significant increase in accuracy scores from
      session 1 to session 3. Age-related trends suggested the mean scores in the
      cursor-based condition were associated with older children consistently
      performing at high levels and younger children remaining at low levels, while
      trends in the animated group were associated with children learning the interface
      in a way not associated with age. Findings support that enhanced presentations of
      scanning can increase the transparency of the scanning interface for some
      children and suggest that contextual scene displays could benefit from animations
      and sound for children not using direct selection.

PMID- 28430028
TI  - Attitudes Toward, and Use of, Vibrators in China.
AB  - The current study examined the relationship between traditional masculine traits
      and attitudes toward vibrator use, actual vibrator use, and frequency of vibrator
      use in China. In all, 235 Chinese females aged between 16 and 58 years completed
      a questionnaire regarding attitudes toward, and personal use of, vibrators. The
      results showed a positive association between masculine traits and attitudes
      toward women's vibrator use, attitudes toward vibrator use and actual vibrator
      use, as well as frequency of vibrator use. The findings revealed an indirect path
      in which masculinity influences actual and frequency of vibrator use through
      attitudes toward women's vibrator use. Limitations and implications of the study
      are discussed.

PMID- 28430029
TI  - Legal Mapping Analysis of State Telehealth Reimbursement Policies.
AB  - BACKGROUND: There exists rapid growth and inconsistency in the telehealth policy
      environment, which makes it difficult to quantitatively evaluate the impact of
      telehealth reimbursement and other policies without the availability of a legal
      mapping database. INTRODUCTION: We describe the creation of a legal mapping
      database of state-level policies related to telehealth reimbursement of
      healthcare services. Trends and characteristics of these policies are presented.
      MATERIALS AND METHODS: Information provided by the Center for Connected Health
      Policy was used to identify statewide laws and regulations regarding telehealth
      reimbursement. Other information was retrieved by using: (1) LexisNexis database,
      (2) Westlaw database, and (3) retrieval from legislative Web sites, historical
      documents, and contacting state officials. We examined policies for live video,
      store-and-forward, and remote patient monitoring (RPM). RESULTS: In the United
      States, there are 24 states with policies regarding reimbursement for live video
      transmission. Fourteen states have store-and-forward policies, and six states
      have RPM-related policies. Mississippi is the only state that requires
      reimbursement for all three types of telehealth transmission modes. Most states
      (47 states) have Medicaid policies regarding live video transmission, followed by
      37 states for store-and-forward and 20 states for RPM. Only 13 states require
      that live video will be reimbursed "consistent with" or at the "same rate" as in
      person services in their Medicaid program. DISCUSSION: There are no widely
      accepted telehealth reimbursement policies across states. They contain diverse
      restrictions and requirements that present complexities in policy evaluation and
      in determining policy effectiveness across states.

PMID- 28430030
TI  - Letter to the Editor. Medicolegal aspects of craniocentric dog attacks.

PMID- 28430031
TI  - Evaluation of multidimensional models of WAIS-IV subtest performance.
AB  - OBJECTIVE: The present study examined the extent to which the covariance
      structure of the WAIS-IV is best accounted for by models that assume that test
      performance is the result of group-level factors and multiple independent general
      factors. METHOD: Structural models with one to four general factors were
      evaluated with either four or five group-level factors. Simulations based on four
      general factors were run to clarify the adequacy of the estimates of the
      allocation of covariance by the models. RESULTS: Four independent general factors
      provided better fit than a single general factor for either model with four or
      five group-level factors. While one of the general factors had much larger
      loadings than all other factors, simulation results suggested that this might be
      an artifact of the statistical procedure rather than a reflection of the nature
      of individual differences in cognitive abilities. CONCLUSIONS: These results
      argue against the contention that clinical interpretation of cognitive test
      batteries should primarily be at the level of general intelligence. It is a
      fallacy to assume that factor analysis can reveal the structure of human
      abilities. Test validity should not be based solely on the results of modeling
      the covariance of test batteries.

PMID- 28430032
TI  - Sociocultural hegemony, gendered identity, and use of traditional and
      complementary medicine in Ghana.
AB  - This study investigated gender differences in the use of traditional and
      complementary medicine (TCM) in Ghana. Using an interviewer-administered
      questionnaire, we collected data from March to June 2013 from 324 randomly
      sampled adults in the Ashanti region. The prevalence of TCM use in the prior 12
      months was 86 percent. Females constituted the majority (61 percent) of TCM
      users. Female TCM users were more likely than male users to have had only a basic
      education, been traders (p ? .0001), and have health insurance (p ? .05). Using
      multiple logistic regression, TCM use was associated with urban residence for
      females (odds ratio [OR] = 7.82; 95 percent confidence interval [CI]: 1.28-47.83)
      but negatively related for males (OR = 0.032; 95 percent CI: 0.002-0.63). Being
      self-employed was associated with TCM use among males (OR = 7.62; 95 percent CI:
      1.22-47.60), while females' TCM use was associated with higher income (OR = 3.72;
      95 percent CI: 1.21-11.48) and perceived efficacy of TCM (OR = 5.60; 95 percent
      CI: 1.78-17.64). The African sociocultural structure vests household decision
      making power in men but apparently not regarding TCM use, and the factors
      associated with TCM use largely differed by gender. These findings provide
      ingredients for effective health policy planning and evaluation. Adoption and
      modernization of TCM should apply a gendered lens.

PMID- 28430033
TI  - Perceived and Actual Behavior in Female Sexual Assertiveness: A Within-Couple
      Analysis in Hong Kong.
AB  - Studies in female sexual assertiveness have generally focused on individuals
      rather than couples, and little research has been conducted in the Chinese
      context. This study examined perceived and actual female sexual assertiveness at
      the couple level, and also explored its impact on marital and sexual satisfaction
      with a representative sample of 770 couples in Hong Kong. The results showed that
      husbands reported a higher level of acceptance of female sexual assertiveness in
      both perception and actual behavior; furthermore, couples reported greater
      congruence in their perception of female sexual initiation than actual behavior.
      Multiple logistic regressions showed that actual female sexual assertiveness, not
      the perception of it, affects both spouses' marital and sexual satisfaction.
      Compared with couples in which neither accepted female sexual initiation in
      practice, husbands where both spouses accepted this were more likely to be
      satisfied with the marriage. Husbands who accepted female sexual refusal whilst
      their wives did not were also more likely to be satisfied with both the marital
      and sexual relationship. Similarly, wives who did accept female sexual
      assertiveness but whose husbands did not were more likely to be satisfied with
      both the marital and sexual relationship.

PMID- 28430034
TI  - UM-Chor1: establishment and characterization of the first validated clival
      chordoma cell line.
AB  - OBJECTIVE Chordomas are rare malignant tumors thought to arise from remnants of
      the notochord. They can be located anywhere along the axial skeleton but are most
      commonly found in the clival and sacrococcygeal regions, where the notochord
      regresses during fetal development. Chordomas are resistant to many current
      therapies, leaving surgery as the primary method of treatment. Cancer cell lines
      have been useful for developing new cancer treatments in a laboratory setting
      that can then be transferred to the clinic, but there are only 4 validated
      chordoma cell lines available. The objective of this work was to establish
      chordoma cell lines from surgical tissue in order to expand the library of lines
      available for laboratory research. METHODS Chordoma tissue from the clivus was
      processed and sorted by flow cytometry to obtain an isolated population of
      chordoma cells. These cells were grown in culture and expanded until enough
      doublings to consider the line established. Identification of a chordoma cell
      line was made with known markers for chordoma, and the line was observed for ALDH
      (aldehyde dehydrogenase) subpopulations and tested in serum-free growth
      conditions as well as in vivo. RESULTS A fifth chordoma cell line, UM-Chor1, was
      successfully established. This is the first chordoma cell line originating from
      the clivus. Validation was confirmed by phenotype and positivity for the chordoma
      markers CD24 and brachyury. The authors also attempted to identify an ALDHhigh
      cell population in UM-Chor1, UCH1, and UCH2 but did not detect a distinct
      population. UM-Chor1 cells were able to form spheroids in serum-free culture,
      were successfully transduced with luciferase, and could be injected parasacrally
      and grown in NOD/SCID mice. CONCLUSIONS The availability of this novel clival
      chordoma cell line for in vitro and in vivo research provides an opportunity for
      developments in treatment against the disease.

PMID- 28430035
TI  - Noninvasive neuromodulation and thalamic mapping with low-intensity focused
      ultrasound.
AB  - OBJECTIVE Ultrasound can be precisely focused through the intact human skull to
      target deep regions of the brain for stereotactic ablations. Acoustic energy at
      much lower intensities is capable of both exciting and inhibiting neural tissues
      without causing tissue heating or damage. The objective of this study was to
      demonstrate the effects of low-intensity focused ultrasound (LIFU) for
      neuromodulation and selective mapping in the thalamus of a large-brain animal.
      METHODS Ten Yorkshire swine ( Sus scrofa domesticus) were used in this study. In
      the first neuromodulation experiment, the lemniscal sensory thalamus was
      stereotactically targeted with LIFU, and somatosensory evoked potentials (SSEPs)
      were monitored. In a second mapping experiment, the ventromedial and
      ventroposterolateral sensory thalamic nuclei were alternately targeted with LIFU,
      while both trigeminal and tibial evoked SSEPs were recorded. Temperature at the
      acoustic focus was assessed using MR thermography. At the end of the experiments,
      all tissues were assessed histologically for damage. RESULTS LIFU targeted to the
      ventroposterolateral thalamic nucleus suppressed SSEP amplitude to 71.6% +/-
      11.4% (mean +/- SD) compared with baseline recordings. Second, we found a similar
      degree of inhibition with a high spatial resolution (~ 2 mm) since adjacent
      thalamic nuclei could be selectively inhibited. The ventromedial thalamic nucleus
      could be inhibited without affecting the ventrolateral nucleus. During MR
      thermography imaging, there was no observed tissue heating during LIFU
      sonications and no histological evidence of tissue damage. CONCLUSIONS These
      results suggest that LIFU can be safely used to modulate neuronal circuits in the
      central nervous system and that noninvasive brain mapping with focused ultrasound
      may be feasible in humans.

PMID- 28430036
TI  - Paradoxical cerebrovascular hemodynamic changes with nicardipine.
AB  - OBJECTIVE Intravenous nicardipine is commonly used for blood pressure reduction
      in patients with acute stroke. However, few studies have described its effects on
      cerebrovascular hemodynamics as measured by transcranial Doppler (TCD) waveform
      analysis and pulsatility index (PI). In this study, the authors report examples
      of a consistent but paradoxical finding associated with nicardipine that suggests
      intracranial vasoconstriction, contrary to what is expected from a vasodilator.
      METHODS The data presented are from a convenience sample of patients who
      underwent TCD monitoring before, after, or during nicardipine administration. In
      each case, TCD waveform morphologies and PIs were compared. RESULTS The TCD
      waveforms during nicardipine infusion are characterized by a prominent systolic
      peak and dicrotic notch. Systolic deceleration was more pronounced and PIs were
      significantly elevated in patients who were on nicardipine (p < 0.001). This
      finding was not evident when patients were not on nicardipine. CONCLUSIONS This
      study provides the first evidence of paradoxical intracranial vasoconstriction
      associated with intravenous nicardipine. In the authors' experience, this finding
      is consistently encountered in the vast majority of patients who are treated with
      intravenous nicardipine, and is contradictory to what is expected from a
      vasodilator. Future studies are needed to confirm this finding in larger
      populations and diverse clinical settings and to examine mechanisms that explain
      this phenomenon.

PMID- 28430037
TI  - Ethical difficulties in the innovative surgical treatment of patients with
      recurrent glioblastoma multiforme.

PMID- 28430038
TI  - Prognostic implications of the subcellular localization of survivin in
      glioblastomas treated with radiotherapy plus concomitant and adjuvant
      temozolomide.
AB  - OBJECTIVE Currently, the standard treatment protocol for patients with newly
      diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and
      adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been
      described, including survivin expression. The aim of this study was to determine
      whether the subcellular localization of survivin correlates with GBM prognosis in
      patients who received the standard treatment protocol. METHODS The authors
      retrospectively examined the subcellular localization of survivin (nuclear,
      cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had
      received the standard treatment. The relationship between survivin localization
      and overall survival (OS) was assessed with uni- and multivariate analyses
      including other clinicopathological factors (age, sex, Karnofsky Performance
      Scale [KPS] score, extent of resection, the use of second-line bevacizumab, O6
      methylguanine-DNA methyltransferase [MGMT] status, and MIB-1 labeling index).
      RESULTS Log-rank tests revealed that patient age, KPS score, extent of resection,
      MGMT status, and survivin localization (p < 0.0001) significantly correlated with
      OS. Multivariate analysis indicated that patient age, MGMT status, and survivin
      localization significantly correlated with OS. Patients with nuclear localization
      of survivin had a significantly shorter OS than those in whom survivin expression
      was exclusively cytoplasmic (median OS 19.5 vs 31.7 months, respectively, HR
      5.690, 95% CI 2.068-17.612, p = 0.0006). There was no significant difference in
      OS between patents whose survivin expression was exclusively nuclear or
      nuclear/cytoplasmic. CONCLUSIONS Nuclear expression of survivin is a factor for a
      poor prognosis in GBM patients. Subcellular localization of survivin can help to
      predict OS in GBM patients treated with the standard protocol.

PMID- 28430039
TI  - Distractor-resistant Short-Term Memory Is Supported by Transient Changes in
      Neural Stimulus Representations.
AB  - Goal-directed behavior in a complex world requires the maintenance of goal
      relevant information despite multiple sources of distraction. However, the brain
      mechanisms underlying distractor-resistant working or short-term memory (STM) are
      not fully understood. Although early single-unit recordings in monkeys and fMRI
      studies in humans pointed to an involvement of lateral prefrontal cortices, more
      recent studies highlighted the importance of posterior cortices for the active
      maintenance of visual information also in the presence of distraction. Here, we
      used a delayed match-to-sample task and multivariate searchlight analyses of fMRI
      data to investigate STM maintenance across three extended delay phases.
      Participants maintained two samples (either faces or houses) across an unfilled
      pre-distractor delay, a distractor-filled delay, and an unfilled post-distractor
      delay. STM contents (faces vs. houses) could be decoded above-chance in all three
      delay phases from occipital, temporal, and posterior parietal areas. Classifiers
      trained to distinguish face versus house maintenance successfully generalized
      from pre- to post-distractor delays and vice versa, but not to the distractor
      delay period. Furthermore, classifier performance in all delay phases was
      correlated with behavioral performance in house, but not face, trials. Our
      results demonstrate the involvement of distributed posterior, but not lateral
      prefrontal, cortices in active maintenance during and after distraction. They
      also show that the neural code underlying STM maintenance is transiently changed
      in the presence of distractors and reinstated after distraction. The correlation
      with behavior suggests that active STM maintenance is particularly relevant in
      house trials, whereas face trials might rely more strongly on contributions from
      long-term memory.

PMID- 28430040
TI  - Foraging Value, Risk Avoidance, and Multiple Control Signals: How the Anterior
      Cingulate Cortex Controls Value-based Decision-making.
AB  - Recent work on the role of the ACC in cognition has focused on choice difficulty,
      action value, risk avoidance, conflict resolution, and the value of exerting
      control among other factors. A main underlying question is what are the output
      signals of ACC, and relatedly, what is their effect on downstream cognitive
      processes? Here we propose a model of how ACC influences cognitive processing in
      other brain regions that choose actions. The model builds on the earlier
      Predicted Response Outcome model and suggests that ACC learns to represent
      specifically the states in which the potential costs or risks of an action are
      high, on both short and long timescales. It then uses those cost signals as a
      basis to bias decisions to minimize losses while maximizing gains. The model
      simulates both proactive and reactive control signals and accounts for a variety
      of empirical findings regarding value-based decision-making.

PMID- 28430041
TI  - Integrative Modeling of Prefrontal Cortex.
AB  - pFC is generally regarded as a region critical for abstract reasoning and high
      level cognitive behaviors. As such, it has become the focus of intense research
      involving a wide variety of subdisciplines of neuroscience and employing a
      diverse range of methods. However, even as the amount of data on pFC has
      increased exponentially, it appears that progress toward understanding the
      general function of the region across a broad array of contexts has not kept
      pace. Effects observed in pFC are legion, and their interpretations are generally
      informed by a particular perspective or methodology with little regard with how
      those effects may apply more broadly. Consequently, the number of specific roles
      and functions that have been identified makes the region a very crowded place
      indeed and one that appears unlikely to be explained by a single general
      principle. In this theoretical article, we describe how the function of large
      portions of pFC can be accommodated by a single explanatory framework based on
      the computation and manipulation of error signals and how this framework may be
      extended to account for additional parts of pFC.

PMID- 28430042
TI  - Control without Controllers: Toward a Distributed Neuroscience of Executive
      Control.
AB  - Executive control refers to the regulation of cognition and behavior by mental
      processes and is a hallmark of higher cognition. Most approaches to understanding
      its mechanisms begin with the assumption that our brains have anatomically
      segregated and functionally specialized control modules. The modular approach is
      intuitive: Control is conceptually distinct from basic mental processing, so an
      organization that reifies that distinction makes sense. An alternative approach
      sees executive control as self-organizing principles of a distributed
      organization. In distributed systems, control and controlled processes are
      colocalized within large numbers of dispersed computational agents. Control then
      is often an emergent consequence of simple rules governing the interaction
      between agents. Because these systems are unfamiliar and unintuitive, here we
      review several well-understood examples of distributed control systems, group
      living insects and social animals, and emphasize their parallels with neural
      systems. We then reexamine the cognitive neuroscience literature on executive
      control for evidence that its neural control systems may be distributed.

PMID- 28430043
TI  - Tuning Neural Phase Entrainment to Speech.
AB  - Musical rhythm positively impacts on subsequent speech processing. However, the
      neural mechanisms underlying this phenomenon are so far unclear. We investigated
      whether carryover effects from a preceding musical cue to a speech stimulus
      result from a continuation of neural phase entrainment to periodicities that are
      present in both music and speech. Participants listened and memorized French
      metrical sentences that contained (quasi-)periodic recurrences of accents and
      syllables. Speech stimuli were preceded by a rhythmically regular or irregular
      musical cue. Our results show that the presence of a regular cue modulates neural
      response as estimated by EEG power spectral density, intertrial coherence, and
      source analyses at critical frequencies during speech processing compared with
      the irregular condition. Importantly, intertrial coherences for regular cues were
      indicative of the participants' success in memorizing the subsequent speech
      stimuli. These findings underscore the highly adaptive nature of neural phase
      entrainment across fundamentally different auditory stimuli. They also support
      current models of neural phase entrainment as a tool of predictive timing and
      attentional selection across cognitive domains.

PMID- 28430044
TI  - Syntactic Complexity and Frequency in the Neurocognitive Language System.
AB  - Prominent neurobiological models of language follow the widely accepted
      assumption that language comprehension requires two principal mechanisms: a
      lexicon storing the sound-to-meaning mapping of words, primarily involving
      bilateral temporal regions, and a combinatorial processor for syntactically
      structured items, such as phrases and sentences, localized in a left-lateralized
      network linking left inferior frontal gyrus (LIFG) and posterior temporal areas.
      However, recent research showing that the processing of simple phrasal sequences
      may engage only bilateral temporal areas, together with the claims of
      distributional approaches to grammar, raise the question of whether frequent
      phrases are stored alongside individual words in temporal areas. In this fMRI
      study, we varied the frequency of words and of short and long phrases in English.
      If frequent phrases are indeed stored, then only less frequent items should
      generate selective left frontotemporal activation, because memory traces for such
      items would be weaker or not available in temporal cortex. Complementary
      univariate and multivariate analyses revealed that, overall, simple words (verbs)
      and long phrases engaged LIFG and temporal areas, whereas short phrases engaged
      bilateral temporal areas, suggesting that syntactic complexity is a key factor
      for LIFG activation. Although we found a robust frequency effect for words in
      temporal areas, no frequency effects were found for the two phrasal conditions.
      These findings support the conclusion that long and short phrases are analyzed,
      respectively, in the left frontal network and in a bilateral temporal network but
      are not retrieved from memory in the same way as simple words during spoken
      language comprehension.

PMID- 28430045
TI  - Laparoscopic Sleeve Gastrectomy Changes in the Last Decade: Differences in
      Morbidity and Weight Loss.
AB  - PURPOSE: Aim is to report the learning curve and standardization process of
      Laparoscopic Sleeve Gastrectomy (LSG), describing the evolution in surgical
      technique and patient management in the authors' experiences. METHODS: One
      hundred twenty-seven patients were divided in three Groups (A, B, and C), based
      on bougie size and technical details, and included 36, 46, and 45 patients,
      respectively. RESULTS: Mean operative time in Groups A, B, and C was 201.5,
      150.8, and 172 minutes, respectively. Conversion to open surgery occurred in 1
      Group A case. Eleven postoperative complications (8.6%) were observed (1 Group A,
      8 Group B, 2 and Group C). Mean hospital stay in Groups A, B, and C, was 7.1,
      6.9, and 3.1 days, respectively. At a mean follow-up of 69.7 months (Group A),
      33.3 months (Group B), and 14.8 months (Group C), mean postoperative body mass
      index is 32.6, 28.1, and 31.5 kg/m2, respectively. Percentage estimated body mass
      index loss (%EBMIL) was 74.8% for Group A, 85.7% for Group B, and 68.1% for Group
      C. CONCLUSIONS: LSG is a safe and effective procedure. In the postoperative
      course, meticulous alertness to early warning signs of sepsis and aggressive
      patient management are mandatory to prevent mortality. The use of a larger bougie
      size was associated with weight regain.

PMID- 28430046
TI  - An Outpatient Methadone Weaning Program by a Neonatal Intensive Care Unit for
      Neonatal Abstinence Syndrome.
AB  - Through retrospective chart review, this study described characteristics and
      length of stay for a cohort of newborns discharged on methadone following an
      inpatient weaning for neonatal abstinence syndrome (NAS). Data were assessed for
      all term infants born between January 1, 2010, and December 31, 2014, admitted to
      the hospital with a co-diagnosis of NAS at discharge, for gestational age, length
      of stay, days on treatment protocol before discharge, time to once-daily interval
      methadone dosing, and hospital charges, as well as for categorical
      characteristics. The 53 patients were predominantly male (58%), white (71%), and
      covered by Medicaid insurance (72%). Mean gestational age was 39.5 +/- 1.1 weeks;
      length of hospital stay was 11.8 +/- 5 days. Common co-diagnoses were newborn
      feeding problems (26%) and neonatal hypoglycemia (23%). In conclusion, use of the
      study site's methadone weaning protocol, which can be easily replicated, resulted
      in a relatively short length of stay and low readmission rates for these
      patients.

PMID- 28430047
TI  - Arf GAPs and molecular motors.
AB  - Arf GTPase-activating proteins (Arf GAPs) were first identified as regulators of
      the small GTP-binding proteins ADP-ribosylation factors (Arfs). The Arf GAPs are
      a large family of proteins in metazoans, outnumbering the Arfs that they
      regulate. The members of the Arf GAP family have complex domain structures and
      some have been implicated in particular cellular functions, such as cell
      migration, or with particular pathologies, such as tumor invasion and metastasis.
      The specific effects of Arfs sometimes depend on the Arf GAP involved in their
      regulation. These observations have led to speculation that the Arf GAPs
      themselves may affect cellular activities in capacities beyond the regulation of
      Arfs. Recently, 2 Arf GAPs, ASAP1 and AGAP1, have been found to bind directly to
      and influence the activity of myosins and kinesins, motor proteins associated
      with filamentous actin and microtubules, respectively. The Arf GAP-motor protein
      interaction is critical for cellular behaviors involving the actin cytoskeleton
      and microtubules, such as cell migration and other cell movements. Arfs, then,
      may function with molecular motors through Arf GAPs to regulate microtubule and
      actin remodeling.

PMID- 28430048
TI  - A spinal epidural abscess due to Streptobacillus moniliformis infection following
      a rat bite: case report.
AB  - The authors describe the case of a 40-year-old man suffering from an epidural
      abscess in the thoracic spine due to a rarely isolated pathogen, Streptobacillus
      moniliformis, the causative agent of rat bite fever. Besides diffuse abdominal
      pain, ataxia, paresthesia, hypesthesia, and enhanced reflexes of the lower
      extremities, the patient suffered from a decreased sensation of bladder filling.
      His history was also positive for a rat bite 6 weeks earlier. Magnetic resonance
      imaging showed an epidural, space-occupying lesion compressing the spinal cord at
      the vertebral levels of T6-8. Neurosurgery revealed an epidural abscess, which
      was drained via laminectomy (T-7) and excision of the ligamentum flavum (T6-8).
      The etiological agent S. moniliformis was identified by 16S rRNA-based polymerase
      chain reaction and sequencing as well as by culture and mass spectrometry.
      Treatment with penicillin G led to complete resolution of the abscess and
      clinical recovery of the patient, who regained his bladder-filling sensation and
      free walking ability. This case demonstrates that careful attention to the
      patient's history is essential in suspecting unusual bacterial pathogens as the
      cause of an epidural abscess and initiating the optimal diagnostic procedure and
      antimicrobial therapy.

PMID- 28430049
TI  - Minimally invasive instrumentation without fusion during posterior thoracic
      corpectomies: a comparison of percutaneously instrumented nonfused segments with
      open instrumented fused segments.
AB  - OBJECTIVE During the mini-open posterior corpectomy, percutaneous instrumentation
      without fusion is performed above and below the corpectomy level. In this study,
      the authors' goal was to compare the perioperative and long-term implant failure
      rates of patients who underwent nonfused percutaneous instrumentation with those
      of patients who underwent traditional open instrumented fusion. METHODS Adult
      patients who underwent posterior thoracic corpectomies with cage reconstruction
      between 2009 and 2014 were identified. Patients who underwent mini-open
      corpectomy had percutaneous instrumentation without fusion, and patients who
      underwent open corpectomy had instrumented fusion above and below the corpectomy
      site. The authors compared perioperative outcomes and rates of implant failure
      requiring reoperation between the open (fused) and mini-open (unfused) groups.
      RESULTS A total of 75 patients were identified, and 53 patients (32 open and 21
      mini-open) were available for followup. The mean patient age was 52.8 years, and
      56.6% of patients were male. There were no significant differences in baseline
      variables between the 2 groups. The overall perioperative complication rate was
      15.1%, and there was no significant difference between the open and mini-open
      groups (18.8% vs 9.5%; p = 0.359). The mean hospital stay was 10.5 days. The open
      group required a significantly longer stay than the mini-open group (12.8 vs 7.1
      days; p < 0.001). Overall implant failure rates requiring reoperation were 1.9%
      at 6 months, 9.1% at 1 year, and 14.7% at 2 years. There were no significant
      differences in reoperation rates between the open and mini-open groups at 6
      months (3.1% vs 0.0%, p = 0.413), 1 year (10.7% vs 6.2%, p = 0.620), and 2 years
      (18.2% vs 8.3%, p = 0.438). The overall mean follow-up was 29.2 months.
      CONCLUSIONS These findings suggest that percutaneous instrumentation without
      fusion in mini-open transpedicular corpectomies offers similar implant failure
      and reoperation rates as open instrumented fusion as far out as 2 years of follow
      up.

PMID- 28430050
TI  - Letter to the Editor. Risk of recurrence of lumbar disc herniation after
      microdiscectomy for scoliosis.

PMID- 28430051
TI  - Reversible postoperative blindness caused by bilateral status epilepticus
      amauroticus following thoracolumbar deformity correction: case report.
AB  - Postoperative vision loss (POVL) is a devastating complication and has been
      reported after complex spine procedures. Anterior ischemic optic neuropathy and
      posterior optic neuropathy are the 2 most common causes of POVL. Bilateral
      occipital lobe seizures causing complete blindness are rare and have not been
      reported as a cause of POVL after spine surgery with the patient prone. The
      authors report the case of a 67-year-old man without a history of seizures who
      underwent a staged thoracolumbar deformity correction and developed POVL 6 hours
      after surgery. Imaging, laboratory, and ophthalmological examination results were
      nonrevealing. Routine electroencephalography study results were negative, but
      continuous electroencephalography captured bilateral occipital lobe seizures. The
      patient developed nonconvulsive status epilepticus despite initial treatment with
      benzodiazepines and loading doses of levetiracetam and lacosamide. He was
      therefore intubated for status epilepticus amauroticus and received a midazolam
      infusion. After electrographic seizure cessation for 48 hours, the patient was
      weaned off midazolam. The patient was maintained on levetiracetam and lacosamide
      without seizure recurrence and returned to his preoperative visual baseline
      status.

PMID- 28430052
TI  - Predicting complication risk in spine surgery: a prospective analysis of a novel
      risk assessment tool.
AB  - OBJECTIVE The ability to assess the risk of adverse events based on known patient
      factors and comorbidities would provide more effective preoperative risk
      stratification. Present risk assessment in spine surgery is limited. An adverse
      event prediction tool was developed to predict the risk of complications after
      spine surgery and tested on a prospective patient cohort. METHODS The spinal Risk
      Assessment Tool (RAT), a novel instrument for the assessment of risk for patients
      undergoing spine surgery that was developed based on an administrative claims
      database, was prospectively applied to 246 patients undergoing 257 spinal
      procedures over a 3-month period. Prospectively collected data were used to
      compare the RAT to the Charlson Comorbidity Index (CCI) and the American College
      of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Surgical
      Risk Calculator. Study end point was occurrence and type of complication after
      spine surgery. RESULTS The authors identified 69 patients (73 procedures) who
      experienced a complication over the prospective study period. Cardiac
      complications were most common (10.2%). Receiver operating characteristic (ROC)
      curves were calculated to compare complication outcomes using the different
      assessment tools. Area under the curve (AUC) analysis showed comparable
      predictive accuracy between the RAT and the ACS NSQIP calculator (0.670 [95% CI
      0.60-0.74] in RAT, 0.669 [95% CI 0.60-0.74] in NSQIP). The CCI was not accurate
      in predicting complication occurrence (0.55 [95% CI 0.48-0.62]). The RAT produced
      mean probabilities of 34.6% for patients who had a complication and 24% for
      patients who did not (p = 0.0003). The generated predicted values were stratified
      into low, medium, and high rates. For the RAT, the predicted complication rate
      was 10.1% in the low-risk group (observed rate 12.8%), 21.9% in the medium-risk
      group (observed 31.8%), and 49.7% in the high-risk group (observed 41.2%). The
      ACS NSQIP calculator consistently produced complication predictions that
      underestimated complication occurrence: 3.4% in the low-risk group (observed
      12.6%), 5.9% in the medium-risk group (observed 34.5%), and 12.5% in the high
      risk group (observed 38.8%). The RAT was more accurate than the ACS NSQIP
      calculator (p = 0.0018). CONCLUSIONS While the RAT and ACS NSQIP calculator were
      both able to identify patients more likely to experience complications following
      spine surgery, both have substantial room for improvement. Risk stratification is
      feasible in spine surgery procedures; currently used measures have low accuracy.

PMID- 28430053
TI  - Issues of Fidelity and Trust Are Intrinsic to Uncontrolled Donation After
      Circulatory Determination of Death and Arise Again With Each New Resuscitation
      Method.

PMID- 28430055
TI  - Ethics, Refugees, and the President's Executive Order.

PMID- 28430054
TI  - Ethical Issues in Fecal Microbiota Transplantion: Taking Into Account Identity
      and Family Relations.

PMID- 28430056
TI  - Greed, Gullibility, and Golden Eggs: FMT and Ethical, Legal, and Practical
      Difficulties Regulating Transactions in Readily Accessed and Exchanged Bodily
      Products.

PMID- 28430057
TI  - How Can You Be Transparent About Labeling the Living as Dead?

PMID- 28430058
TI  - Fecal Transplant Bioethics: Beyond Chicken Little.

PMID- 28430059
TI  - Whose Autonomy? Which Obligations? Preserving the Right to (Professional) Self
      Determination at the Margins of Viability.

PMID- 28430060
TI  - Cultural and Personal Considerations in Informed Consent for Fecal Microbiota
      Transplantation.

PMID- 28430061
TI  - Frozen Ethics: Melting the Boundaries Between Medical Treatment and Organ
      Procurement.

PMID- 28430062
TI  - Resuscitation Versus Donation: Conflict, Priority, and Rational Consent.

PMID- 28430064
TI  - Aesthetics, Ethics, and Fecal Microbiota Transplantations.

PMID- 28430063
TI  - FMT Regulatory Challenges and the Lived Experiences of People With IBD.

PMID- 28430065
TI  - Ethical Issues in Fecal Microbiota Transplantation in Practice.
AB  - Fecal microbiota transplantation (FMT) has demonstrated efficacy and is
      increasingly being used in the treatment of patients with recurrent Clostridium
      difficile infection. Despite a lack of high-quality trials to provide more
      information on the long-term effects of FMT, there has been great enthusiasm
      about the potential for expanding its applications. However, FMT presents many
      serious ethical and social challenges that must be addressed as part of a
      successful regulatory policy response. In this article, we draw on a sample of
      the scientific and bioethics literatures to examine clusters of ethical and
      social issues arising in five main areas: (1) informed consent and the
      vulnerability of patients; (2) determining what a "suitable healthy donor" is;
      (3) safety and risk; (4) commercialization and potential exploitation of
      vulnerable patients; and (5) public health implications. We find that these
      issues are complex and worthy of careful consideration by health care
      professionals. Desperation of a patient should not be the basis for selecting
      treatment with FMT, and the patient's interests should always be of paramount
      concern. Authorities must prioritize development of appropriate and effective
      regulation of FMT to safeguard patients and donors, promote further research into
      safety and efficacy, and avoid abuse of the treatment.

PMID- 28430066
TI  - Cautions for Extending Fecal Microbiota Transplantation to Other Therapeutic
      Uses.

PMID- 28430067
TI  - Declare Death or Attempt Experimental Resuscitation?

PMID- 28430068
TI  - Caring for Patients or Organs: New Therapies Raise New Dilemmas in the Emergency
      Department.
AB  - Two potentially lifesaving protocols, emergency preservation and resuscitation
      (EPR) and uncontrolled donation after circulatory determination of death (uDCDD),
      currently implemented in some U.S. emergency departments (EDs), have similar
      eligibility criteria and initial technical procedures, but critically different
      goals. Both follow unsuccessful cardiopulmonary resuscitation and induce
      hypothermia to "buy time": one in trauma patients suffering cardiac arrest, to
      enable surgical repair, and the other in patients who unexpectedly die in the ED,
      to enable organ donation. This article argues that to fulfill patient-focused
      fiduciary obligations and maintain community trust, institutions implementing
      both protocols should adopt and publicize policies to guide ED physicians to
      utilize either protocol for particular patients, in order to address the
      appearance of conflict of interest arising from the protocols' similarities. It
      concludes by analyzing ethical implications of incentives that may influence
      institutions to develop the expertise required for uDCDD but not EPR.

PMID- 28430070
TI  - Using Technology to Facilitate Better Community Consultation With Marginalized
      Communities.

PMID- 28430069
TI  - Saving the Dead.

PMID- 28430071
TI  - Genetic Fingerprints and National Security.

PMID- 28430072
TI  - Nonexceptionalism, Research Risks, and Social Media: Response to Open Peer
      Commentaries on "Using Social Media as a Research Recruitment Tool: Ethical
      Issues and Recommendations".

PMID- 28430073
TI  - Physicians Must Discuss Potential Long-Term Risks of Fecal Microbiota
      Transplantation to Ensure Informed Consent.

PMID- 28430075
TI  - Considerations in the management of congenital cranial dermoid cysts.
AB  - OBJECTIVE Congenital dermoid cysts (CDCs) develop from the entrapment of the
      surface ectoderm along the lines of embryonic fusion and have a capacity to grow.
      Given this capacity for continual expansion, the timing of removal and
      anticipation of possible epidural extension is important. METHODS The authors
      retrospectively reviewed records of patients with the diagnosis of dermoid cyst
      presenting over a period of 10 years. Baseline characteristics, histological
      reports, and surgical records were collected and analyzed. Only those patients
      with histological confirmation of dermoid cyst were included in the study.
      RESULTS One hundred fifty-nine (64 male and 95 female) patients were studied. The
      average age at the time of surgery ranged from 1 month to 63 years (mean 3.55 +/-
      9.58 years, median 11 months). Eighteen (11.3%) CDCs were in the midline anterior
      fontanelle, 52 (32.7%) were frontozygomatic, 14 (8.8%) occurred along the coronal
      sutures, and 75 (47.2%) occurred along the lambdoid sutures. In 74 (46.5%) cases
      the cysts were found to insignificantly erode the cranium, 30 (18.9%) eroded
      through a partial thickness of the cranium, 47 (29.6%) eroded through the full
      thickness of the cranium, and 8 (5.0%) eroded through the full thickness of the
      cranium and demonstrated epidural extension. The study population showed female
      predominance (n = 95, 59.7%). Although cyst location and patient sex were not
      found to vary significantly with cranial involvement (p = 0.196 and p = 0.066,
      respectively), delay in time to surgery did vary significantly (p < 0.00001).
      CONCLUSIONS Congenital cranial dermoid cysts found in infants and children are
      best removed early.

PMID- 28430076
TI  - On using distributional analysis techniques for determining the onset of the
      influence of experimental variables.
AB  - Much of the investigation of eye-movement control in visual cognition has focused
      on the influence of experimental variables on mean fixation durations. In the
      present paper we explored the convergence between two distributional analysis
      techniques that were recently introduced in this domain. First, Staub, White,
      Drieghe, Hollway and Rayner, (2010) proposed fitting the ex-Gaussian distribution
      to individual participants' data in order to ascertain whether a variable has a
      rapid or a slow influence on fixation durations. Second, the Divergence Point
      Analysis (DPA) procedure was introduced by Reingold, Reichle, Glaholt and
      Sheridan (2012, Reingold & Sheridan, 2014) in order to determine more precisely
      the earliest discernible impact of a variable on the distribution of fixation
      durations by contrasting survival curves across two experimental conditions and
      determining the point at which the two curves begin to diverge. In the present
      paper we introduced a new version of the DPA procedure which is based on ex
      Gaussian fitting. We evaluated this procedure by re-analysing data obtained in
      previous empirical investigations as well as by conducting a simulation study. We
      demonstrated that the new ex-Gaussian DPA technique produced estimates that were
      consistent with estimates produced by prior versions of DPA procedure, and in the
      present simulation, the ex-Gaussian DPA procedure produced somewhat more accurate
      individual participant divergence point estimates. Based on the present findings
      we also suggest guidelines for best practices in the use of DPA techniques.

PMID- 28430078
TI  - Monoclonal Antibody: 5C9H2 Against Human Ghrelin Receptor.

PMID- 28430079
TI  - Monoclonal Antibody AbCR1 Against Guinea Pig CXCR1 and Monoclonal Antibody AbCR2
      Against Guinea Pig CXCR2.

PMID- 28430080
TI  - Generation and Characterization of Inhibitory Antibodies Specific to Guinea Pig
      CXCR1 and CXCR2.
AB  - CXCR1 and CXCR2 are chemokine receptors that have different selectivity of
      chemokine ligands, but the distinct role of each receptor is not clearly
      understood. This is due to the absence of specific inhibitors in guinea pigs,
      which are the appropriate species for investigation of CXCR1 and CXCR2 because of
      their functional similarity to humans. In this study, we generated and evaluated
      monoclonal antibodies that specifically bound to guinea pig CXCR1 (gpCXCR1) and
      guinea pig CXCR2 (gpCXCR2) for acquisition of specific inhibitors. To assess the
      activity of antibodies, we established CHO-K1 cells stably expressing either
      gpCXCR1 or gpCXCR2 (CHO/gpCXCR1 or CHO/gpCXCR2). CHO/gpCXCR1 showed migration in
      response to guinea pig interleukin (IL)-8, and CHO/gpCXCR2 showed migration in
      response to both guinea pig IL-8 and guinea pig growth-regulated oncogene alpha.
      The receptor selectivities of the chemokines of guinea pigs were the same as the
      human orthologs. The inhibitory activities of the anti-gpCXCR1 and anti-gpCXCR2
      monoclonal antibodies on cell migration were observed in a concentration
      dependent manner. In conclusion, we successfully obtained inhibitory antibodies
      specific to gpCXCR1 and gpCXCR2. These inhibitory antibodies will be useful to
      clarify the physiological roles of CXCR1 and CXCR2 in guinea pigs.

PMID- 28430081
TI  - Prevalence and Factors Associated With Criminal Behavior Among Illicit Drug
      Users: A Cross-Sectional Study.
AB  - BACKGROUND: Studies indicate high rates of criminal behavior, violent activities,
      and legal problems among illicit drug users (IDU) in Brazil. The aim of this
      study was to estimate the prevalence and factors associated with criminal
      behavior among IDU undergoing treatment for chemical dependency in Central
      Brazil. METHODS: Cross-sectional study carried out with IDU undergoing treatment
      for chemical dependence. Data were collected by means of face-to-face interviews
      and analyzed using logistic regression. RESULTS: Of the total participants (n =
      274), 46.7%, 15.7%, and 10.9% reported involvement in robbery, drug trafficking
      and homicide, respectively. Robbery was associated with young age, withdrawal
      symptoms, prison record, sex work, and crack use, while drug trafficking was
      associated with young age, low education, and marijuana use. Homicides were
      associated with cocaine and marijuana use. CONCLUSION: The results show high
      rates of criminal behavior among drug users, demonstrating associations between
      socio-demographic and behavioral characteristics, illicit drug use, and practices
      of illegal activities. These variables must be considered when planning programs
      and policies to reduce harm related to drug use and abuse.

PMID- 28430077
TI  - Host-Pathogen interactions modulated by small RNAs.
AB  - Biological processes such as defense mechanisms and microbial offense strategies
      are regulated through RNA induced interference in eukaryotes. Genetic mutations
      are modulated through biogenesis of small RNAs which directly impacts upon host
      development. Plant defense mechanisms are regulated and supported by a
      diversified group of small RNAs which are involved in streamlining several RNA
      interference pathways leading toward the initiation of pathogen gene silencing
      mechanisms. In the similar context, pathogens also utilize the support of small
      RNAs to launch their offensive attacks. Also there are strong evidences about the
      active involvement of these RNAs in symbiotic associations. Interestingly, small
      RNAs are not limited to the individuals in whom they are produced; they also show
      cross kingdom influences through variable interactions with other species thus
      leading toward the inter-organismic gene silencing. The phenomenon is
      understandable in the microbes which utilize these mechanisms to overcome host
      defense line. Understanding the mechanism of triggering host defense strategies
      can be a valuable step toward the generation of disease resistant host plants. We
      think that the cross kingdom trafficking of small RNA is an interesting insight
      that is needed to be explored for its vitality.

PMID- 28430082
TI  - A community-based survey on Syrian refugee women's health and its predictors in
      Sanliurfa, Turkey.
AB  - Reproductive characteristics, mental health symptoms, micronutrient deficiencies,
      and symptoms of sexually transmitted infections (STIs) were determined among
      married Syrian refugee women aged 15-49 years who were living outside of camps in
      2015, using probability sampling. Of the 458 participants, 51.3 percent married
      before the age of 18 years. Early-age marriages and number of desired children
      increased after the war. In multivariable analyses, education (adjusted odds
      ratio [aOR] = 1.2; 95% confidence interval [CI] = 1.2-1.3) and length of stay in
      Sanliurfa (aOR = 1.2; 95% CI = 1.1-1.2) were independently associated with early
      marriage. Approximately 16 percent of women were pregnant, and 26.7 percent of
      them had not received prenatal care; 47.7 percent had had a pregnancy loss; 50.8
      percent reported symptoms of STIs. Of those who were sexually active, 37.8
      percent were not using contraception. The prevalence of iron, B12, and folic acid
      deficiencies was 50 percent, 45.6 percent, and 10.5 percent, respectively. Early
      marriage (aOR = 2.2; 95% CI = 1.4-3.5) and number of desired children (aOR =
      5.03; 95% CI = 3.2-7.9) were associated with not using contraception. Most (89.7
      percent) women reported at least two mental health symptoms; lack of social
      support (aOR = 2.6; 95% CI = 1.3-5.3), language barrier (aOR = 2.3; 95% CI = 1.01
      5.2), and B12 deficiency (aOR = 1.8; 95% CI = 1.01-3.4) were associated with such
      symptoms. The findings demonstrate the need for reproductive health and
      psychosocial services.

PMID- 28430083
TI  - Hydrocephalus treatment in children: long-term outcome in 975 consecutive
      patients.
AB  - OBJECTIVE Hydrocephalus remains one of the more common pathologies managed in
      pediatric neurosurgical units. Endoscopic third ventriculostomy (ETV) has an
      advantage over ventriculoperitoneal shunting as it enables patients to remain
      device free. Multiple shunt devices with various valve designs exist, with no one
      valve proven to be superior to another. The aim of this study was to describe the
      management of hydrocephalus and its long-term outcome. METHODS The authors
      retrospectively reviewed the medical records of all patients who had been treated
      for hydrocephalus at the Hopital Necker-Enfants Malades in the period from 1985
      to 1995. RESULTS Nine hundred seventy-five children had been treated for
      hydrocephalus. The mean follow-up was 11 +/- 7.4 years (mean +/- standard
      deviation). The most common cause of hydrocephalus was tumor related (32.3%),
      followed by malformative (24.5%) and inflammatory (20.9%) causes. Two hundred
      eighty patients underwent ETV as the first-line treatment. The procedure was
      effective in controlling hydrocephalus due to posterior fossa tumors and
      aqueductal stenosis. Six hundred ninety-five children had initial shunt
      insertion, with the majority receiving an Orbis-Sigma valve (OSV). The overall
      OSV shunt survival was 70% at 1 year, 58% at 10 years, and 49% at 20 years. The
      most common cause for mechanical shunt failure was obstruction (50.7%). Overall
      shunt survival was statistically different between the OSV and the differential
      pressure valve (p = 0.009). CONCLUSIONS Endoscopic third ventriculostomy is
      effective in the management of childhood hydrocephalus. Its success is directly
      related to the underlying pathology. In the long term, the OSV has significantly
      higher event-free shunt survival than the classic differential-pressure valve
      systems.

PMID- 28430084
TI  - The spo0A-sinI-sinR Regulatory Circuit Plays an Essential Role in Biofilm
      Formation, Nematicidal Activities, and Plant Protection in Bacillus cereus AR156.
AB  - The rhizosphere bacterium Bacillus cereus AR156 is capable of forming biofilms,
      killing nematodes, and protecting plants. However, the underlying molecular
      mechanisms of these processes are not well understood. In this study, we found
      that the isogenic mutants DeltaBcspo0A and DeltaBcsinI have significantly reduced
      colonization and nematicidal activity in vitro and biological control efficacy on
      the tomato plant under greenhouse conditions. We further investigated the role of
      the spo0A-sinI-sinR regulatory circuit in biofilm formation, killing against
      nematodes, and biological control in AR156. Results from mutagenesis of those
      regulatory genes in AR156 and their heterologous expression in B. subtilis
      suggested that the spo0A-sinI-sinR genetic circuit is not only essential for
      biofilm formation and cell differentiation in AR156 but also able to functionally
      replace their counterparts in B. subtilis in a nearly indistinguishable fashion.
      Genome-wide transcriptional profiling in the wild type and the DeltaBcspo0A and
      DeltaBcsinI mutants further revealed hundreds of differentially expressed genes,
      likely positively regulated by both Spo0A and SinI (via SinR) in AR156. Among
      them, 29 genes are predicted to be directly controlled by SinR, whose counterpart
      in B. subtilis is a biofilm master repressor. Collectively, our studies
      demonstrated the essential role of the spo0A-sinI-sinR regulatory circuit in
      biofilm formation, cell differentiation, and bacteria-host interactions in B.
      cereus AR156.

PMID- 28430085
TI  - Investigation of latent infections caused by cyprinid herpesvirus 3 in koi (
      Cyprinus carpio) in southern China.
AB  - Although herpesviruses such as cyprinid herpesvirus 3 (CyHV-3) can establish
      lifelong latent infections, little is known about latency conditions in farmed
      koi populations in China. We used nested polymerase chain reaction targeting the
      TK gene and an indirect antibody ELISA to screen asymptomatic fish obtained from
      southern China for evidence of CyHV-3 infection. CyHV-3 DNA could be detected
      either in peripheral blood leukocytes or from gills of asymptomatic koi. Most koi
      sera did not contain anti-CyHV-3 antibodies; however, 5 samples were ELISA
      positive, providing evidence of prior CyHV-3 infections. These findings suggest
      that koi may survive CyHV-3 infections and become virus carriers.

PMID- 28430086
TI  - Genotypic relatedness and antimicrobial resistance of Salmonella Heidelberg
      isolated from chickens and turkeys in the midwestern United States.
AB  - Salmonella is one of the most common causes of foodborne illnesses in humans in
      the United States, and domestic poultry is considered an important source of this
      pathogen. Salmonella enterica subsp. enterica serovar Heidelberg is the fourth
      most commonly reported Salmonella from retail meats and food animals in the
      United States. We assessed the genotypes and antimicrobial resistance phenotypes
      of Salmonella Heidelberg isolated from various chicken and turkey hatcheries and
      breeder farms in the Midwest. The genotypes of 33 S. Heidelberg isolates from
      chickens ( n = 19) and turkeys ( n = 14) were compared using pulsed-field gel
      electrophoresis analysis. Cluster analysis of the fingerprints showed that the
      majority of the chicken isolates grouped together with 87% similarity; those from
      turkeys clustered with 88% similarity. Similarity between chicken and turkey
      isolates was also high (86%). Isolates from turkeys were generally more
      genetically diverse than those from chickens. Antimicrobial susceptibility
      analysis detected resistance to sulfisoxazole (36% of the isolates), streptomycin
      (33%), gentamicin (27%), tetracycline (24%), ampicillin and amoxicillin
      clavulanic acid (15%), cefoxitin (12%), ceftriaxone and ceftiofur (12%), and
      chloramphenicol (9%). None of the isolates was resistant to azithromycin,
      ciprofloxacin, or nalidixic acid. Although the number of the isolates was limited
      in our study, we conclude that S. Heidelberg isolates from the same host
      generally clustered together and that a considerable number of the isolates were
      resistant to a number of antimicrobial agents.

PMID- 28430087
TI  - Modification of two capripoxvirus quantitative real-time PCR assays to improve
      diagnostic sensitivity and include beta-actin as an internal positive control.
AB  - Capripoxviruses (CaPVs), consisting of Sheeppox virus (SPV), Goatpox virus (GPV),
      and Lumpy skin disease virus (LSDV) species, cause economically significant
      diseases in sheep, goats, and cattle, respectively. Quantitative real-time
      polymerase chain reaction (qPCR) assays are routinely used for rapid detection of
      CaPVs in surveillance and outbreak management programs. We further modified and
      optimized 2 previously published CaPV qPCR assays, referred to as the Balinsky
      and Bowden assays, by changing commercial PCR reagents used in the tests. The
      modified assays displayed 100% analytical specificity and showed no apparent
      changes in analytical sensitivities for detection of CaPVs compared with the
      original assays. Diagnostic sensitivities, assessed using 50 clinical reference
      samples from experimentally infected sheep, goats, and cattle, improved from 82%
      to 92% for the modified Balinsky assay and from 58% to 82% for the modified
      Bowden assay. The modified qPCR assays were multiplexed for detection of beta
      actin as an indicator for potential false-negative results. The multiplex
      modified qPCR assays exhibited the same diagnostic sensitivities as the
      singleplex assays suggesting their utility in the detection of CaPVs.

PMID- 28430089
TI  - Editorial: Giving HTS Structure and an Added Dimension.

PMID- 28430090
TI  - Editorial (Thematic Issue: Uterine Innervation and Clinical Features in
      Obstetrics & Gynecology).

PMID- 28430091
TI  - Foreword.

PMID- 28430092
TI  - Preface.

PMID- 28430093
TI  - Editorial: Brain Imaging and Automatic Analysis in Neurological and Psychiatric
      Diseases - Part I.

PMID- 28430094
TI  - Predictors for the Number of Warning Information Sources During Tornadoes.
AB  - People may receive tornado warnings from multiple information sources, but little
      is known about factors that affect the number of warning information sources
      (WISs). This study examined predictors for the number of WISs with a telephone
      survey on randomly sampled residents in Tuscaloosa, Alabama, and Joplin,
      Missouri, approximately 1 year after both cities were struck by violent tornadoes
      (EF4 and EF5) in 2011. The survey included 1006 finished interviews and the
      working sample included 903 respondents. Poisson regression and Zero-Inflated
      Poisson regression showed that older age and having an emergency plan predicted
      more WISs in both cities. Education, marital status, and gender affected the
      possibilities of receiving warnings and the number of WISs either in Joplin or in
      Tuscaloosa. The findings suggest that social disparity affects the access to
      warnings not only with respect to the likelihood of receiving any warnings but
      also with respect to the number of WISs. In addition, historical and social
      contexts are important for examining predictors for the number of WISs. We
      recommend that the number of WISs should be regarded as an important measure to
      evaluate access to warnings in addition to the likelihood of receiving warnings.
      (Disaster Med Public Health Preparedness. 2017;11:168-172).

PMID- 28430095
TI  - Window of Opportunity for New Disease Surveillance: Developing Keyword Lists for
      Monitoring Mental Health and Injury Through Syndromic Surveillance.
AB  - Studies have documented the impact that hurricanes have on mental health and
      injury rates before, during, and after the event. Since timely tracking of these
      disease patterns is crucial to disaster planning, response, and recovery,
      syndromic surveillance keyword filters were developed by the New York State
      Department of Health to study the short- and long-term impacts of Hurricane
      Sandy. Emergency department syndromic surveillance is recognized as a valuable
      tool for informing public health activities during and immediately following a
      disaster. Data typically consist of daily visit reports from hospital emergency
      departments (EDs) of basic patient data and free-text chief complaints. To
      develop keyword lists, comparisons were made with existing CDC categories and
      then integrated with lists from the New York City and New Jersey health
      departments in a collaborative effort. Two comprehensive lists were developed,
      each containing multiple subcategories and over 100 keywords for both mental
      health and injury. The data classifiers using these keywords were used to assess
      impacts of Sandy on mental health and injuries in New York State. The lists will
      be validated by comparing the ED chief complaint keyword with the final ICD
      diagnosis code. (Disaster Med Public Health Preparedness. 2017;11:173-178).

PMID- 28430096
TI  - Psychological Distress and the Risk of Withdrawing From Hypertension Treatment
      After an Earthquake Disaster.
AB  - OBJECTIVE: This study examined the association between psychological distress and
      the risk of withdrawing from hypertension treatment (HTTx) 1 year after the
      earthquake disaster in the coastal area affected by the Great East Japan
      Earthquake (GEJE). METHODS: Using cross-sectional data from 2012, we studied
      people over 20 years of age living in Shichigahama Town, Miyagi, on the
      northeastern coast of Japan, which had been severely inundated by the tsunami
      that followed the GEJE in 2011. A total of 1014 subjects were categorized as in
      need of HTTx. Withdrawing from HTTx was assessed by using a self-reported
      questionnaire. RESULTS: Subjects with a higher degree of psychological distress
      (Kessler-6 [K6] score >= 13) exhibited a significantly higher risk of withdrawing
      from HTTx, compared with subjects with a lower degree of psychological distress
      (K6 score <= 12; odds ratio=4.0; 95% confidence interval: 1.3-10.6, P<0.01).
      CONCLUSIONS: This study indicated that psychological distress is a risk factor
      for withdrawing from HTTx in post-disaster settings. Our data suggested that the
      increased risk of withdrawing from HTTx associated with post-disaster
      psychological distress may underlie the increased prevalence of vascular diseases
      after the earthquake disaster in coastal areas affected by the tsunami. (Disaster
      Med Public Health Preparedness. 2017;11:179-182).

PMID- 28430097
TI  - Zika Virus Update: More on an Emerging Arboviral Disease in the Western
      Hemisphere.
AB  - Zika virus has captivated the world with its quick spread throughout the Western
      Hemisphere. Increased emphasis has been placed on the infection of pregnant women
      and subsequent adverse and severe effects in the developing fetus and newborn.
      This article supplements a previous article and provides updated information on
      new and evolving evidence that strengthens the association between Zika virus and
      unique congenital and neurologic diseases, updates what is known about the
      epidemiology of the disease, and provides new and updated material for primary
      care providers as they counsel patients who may be exposed or infected. With the
      extent of disease spread, it is expected that Zika virus will become endemic to
      the Western Hemisphere and will change the public health parameters and approach
      in this area of the world. (Disaster Med Public Health Preparedness. 2017;11:163
      167).

PMID- 28430098
TI  - Building Physician Networks as Part of the Zika Response.
AB  - The global community needs to easily identify and respond to new and reemerging
      threats, such as H1N1, Ebola, and most recently Zika. Clinicians are often the
      first-line providers to recognize these threats, but yet have few opportunities
      to learn from each other in real time. In this concept article, we describe the
      ways clinical information is traditionally shared during a public health
      emergency and then introduce new mechanisms to facilitate physician communication
      and learning as a part of the response to Zika. (Disaster Med Public Health
      Preparedness. 2017;11:259-261).

PMID- 28430099
TI  - Mutual interaction enables the mycobacterial plasmid pAL5000 origin binding
      protein RepB to recruit RepA, the plasmid replicase, to the origin.
AB  - The Mycobacterium fortuitum plasmid, pAL5000, is the most-studied member of a
      family of plasmids that are found in Actinobacteria. Its replication is brought
      about by the combined action of two plasmid-encoded replication proteins, RepA
      and RepB. RepB has earlier been shown to be a sigma factor homologue that
      possesses origin-binding activity. The mechanism by which RepA functions, and its
      relationship with RepB, if any, has not been explored yet. In this study, we show
      that RepA shares a common catalytic domain, with proteins belonging to the
      primase-polymerase and DNA polymerase X families. We demonstrate that RepA is
      functionally a DNA polymerase and that mutations that alter two conserved
      aspartic acid residues present within the catalytic core lead to inactivation of
      plasmid replication. Replication of pAL5000 was shown not to depend on the host
      primase, and thus it is most likely that RepA is responsible for the priming act.
      We further demonstrate that RepA and RepB function as a pair and that the
      functional cooperation between the two requires physical contact. The C-terminal
      domain of RepA, which is structurally a helical bundle, is responsible for
      unwinding the origin in a site-specific manner and also for the establishment of
      contacts with RepB. The results presented show that RepB functions by recruiting
      RepA to the origin in much the same way as sigma factors recruit RNA polymerase
      core enzyme to promoters.

PMID- 28430100
TI  - Discovery of African bat polyomaviruses and infrequent recombination in the large
      T antigen in the Polyomaviridae.
AB  - Bat species represent natural reservoirs for a number of high-consequence human
      pathogens. The present study investigated the diversity of polyomaviruses (PyVs)
      in Zambian insectivorous and fruit bat species. We describe the complete genomes
      from four newly proposed African bat PyV species employing the recently
      recommended criteria provided by the Polyomaviridae Study Group of the
      International Committee on Taxonomy of Viruses. A comprehensive phylogenetic and
      recombination analysis was performed to determine genetic relationships and the
      distribution of recombination events in PyV from mammalian and avian species. The
      novel species of PyV from Zambian bats segregated with members of the genera
      Alphapolyomavirus and Betapolyomavirus, forming monophyletic clades with bat and
      non-human primate PyVs. Miniopterus schreibersii polyomavirus 1 and 2 segregated
      in a clade with South American bat PyV species, Old World monkey and chimpanzee
      PyVs and Human polyomavirus 13 (New Jersey PyV). Interestingly, the newly
      described Egyptian fruit bat PyV, tentatively named Rousettus aegyptiacus
      polyomavirus 1, had the highest nucleotide sequence identity to species of PyV
      from Indonesian fruit bats, and Rhinolophus hildebrandtii polyomavirus 1 was most
      closely related to New World monkey PyVs. The distribution of recombination
      events in PyV genomes was non-random: recombination boundaries existed in the
      intergene region between VP1 and LTAg and also at the 3' end of VP2/3 in the
      structural genes, whereas infrequent recombination was present within the LTAg
      gene. These findings indicate that recombination within the LTAg gene has been
      negatively selected against during polyomaviral evolution and support the recent
      proposal for taxonomic classification based on LTAg to define novel PyV species.

PMID- 28430101
TI  - Synthetic temperature-inducible lethal gene circuits in Escherichia coli.
AB  - Temperature sensitivity is often used as a way to attenuate micro-organisms to
      convert them into live vaccines. In this work, we explore the use of temperature
      sensitive (TS) genetic circuits that express lethal genes as a widely applicable
      approach to TS attenuation. We tested different combinations of TS repressors and
      cognate promoters controlling the expression of genes encoding restriction
      endonucleases inserted at four different non-essential sites in the Escherichia
      coli chromosome. We found that the presence of the restriction endonuclease genes
      did not affect the viability of the host strains at the permissive temperature,
      but that expression of the genes at elevated temperatures killed the strains to
      varying extents. The chromosomal insertion site of the lethal cassettes affected
      their functionality, and insertion at one site, ycgH, rendered them ineffective
      at inducing death at high temperature. Induction of a TS circuit in a growing
      culture led to a reduced cell mass and a reduction of the number of cells that
      could exclude a dye that indicated viability. Incubation of cells carrying a TS
      lethal gene circuit initially grown at low temperature and then suspended in
      phosphate buffered saline at high temperature led to about 100-fold loss of cell
      viability per day, compared to a minimal loss of viability for the parental
      strain. Strains carrying either one or two TS lethal circuits could generate
      mutants that survived at high temperature. These mutants included complete
      deletions of the lethal gene circuits.

PMID- 28430102
TI  - Variable virulence phenotype of Xenorhabdus bovienii (gamma-Proteobacteria:
      Enterobacteriaceae) in the absence of their vector hosts.
AB  - Xenorhabdus bovienii bacteria have a dual lifestyle: they are mutualistic
      symbionts to many species of Steinernema nematodes and are pathogens to a wide
      array of insects. Previous studies have shown that virulence of X.bovienii
      Steinernema spp. pairs decreases when the nematodes associate with non-cognate
      bacterial strains. However, the virulence of the X. bovienii strains alone has
      not been fully investigated. In this study, we characterized the virulence of
      nine X. bovienii strains in Galleria mellonella and Spodoptera littoralis and
      performed a comparative genomic analysis to correlate observed phenotypes with
      strain genotypes. Two X. bovienii strains were found to be highly virulent
      against the tested insect hosts, while three strains displayed attenuated insect
      virulence. Comparative genomic analyses revealed the presence of several clusters
      present only in virulent strains, including a predicted type VI secretion system
      (T6SS). We performed intra-species-competition assays, and showed that the
      virulent T6SS+ strains generally outcompeted the less virulent T6SS- strains.
      Thus, we speculate that the T6SS in X. bovienii may be another addition to the
      arsenal of antibacterial mechanisms expressed by these bacteria in an insect,
      where it could potentially play three key roles: (1) competition against the
      insect host microbiota; (2) protection of the insect cadaver from necrotrophic
      microbial competitors; and (3) outcompeting other Xenorhabdus species and/or
      strains when co-infections occur.

PMID- 28430103
TI  - Genomic Characterization of Recrudescent Plasmodium malariae after Treatment with
      Artemether/Lumefantrine.
AB  - Plasmodium malariae is the only human malaria parasite species with a 72-hour
      intraerythrocytic cycle and the ability to persist in the host for life. We
      present a case of a P. malariae infection with clinical recrudescence after
      directly observed administration of artemether/lumefantrine. By using whole
      genome sequencing, we show that the initial infection was polyclonal and the
      recrudescent isolate was a single clone present at low density in the initial
      infection. Haplotypic analysis of the clones in the initial infection revealed
      that they were all closely related and were presumably recombinant progeny
      originating from the same infective mosquito bite. We review possible
      explanations for the P. malariae treatment failure and conclude that a 3-day
      artemether/lumefantrine regimen is suboptimal for this species because of its
      long asexual life cycle.

PMID- 28430104
TI  - Dissection of the interaction between the intrinsically disordered YAP protein
      and the transcription factor TEAD.
AB  - TEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the
      Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon
      binding to TEAD proteins, stimulates their transcriptional activity. Since the
      Hippo pathway is deregulated in various cancers, designing inhibitors of the
      YAP:TEAD interaction is an attractive therapeutic strategy for oncology.
      Understanding the molecular events that take place at the YAP:TEAD interface is
      therefore important not only to devise drug discovery approaches, but also to
      gain knowledge on TEAD regulation. In this report, combining single site-directed
      mutagenesis and double mutant analyses, we conduct a detailed analysis on the
      role of several residues located at the YAP:TEAD interface. Our results provide
      quantitative understanding of the interactions taking place at the YAP:TEAD
      interface and give insights into the formation of the YAP:TEAD complex and more
      particularly on the interaction between TEAD and the Omega-loop found in YAP.

PMID- 28430106
TI  - Atomic motions in the layered copper pseudochalcogenide CuNCN indicative of a
      quantum spin-liquid scenario.
AB  - We explore the thermodynamic properties of the layered copper(II) carbodiimide
      CuNCN by heat-capacity measurements and investigate the corresponding thermal
      atomic motions by means of neutron powder diffraction as well as inelastic
      neutron scattering. The experiments are complemented by a combination of density
      functional calculations, phonon analysis and analytic theory. The existence of a
      soft flexural mode-bending of the layers, characteristic for the material
      structure-is established in the phonon spectrum of CuNCN by giving characteristic
      temperature-dependent contributions to the heat capacity and atomic displacement
      parameters. The agreement with the neutron data allows us to extract a residual
      on top of the lattice-presumably spinon contribution to the heat capacity
      [Formula: see text], speaking in favor of the spin-liquid picture of the
      electronic phases of CuNCN.

PMID- 28430107
TI  - Superconductivity and magnetic fluctuations developing in the vicinity of strong
      first-order magnetic transition in CrAs.
AB  - We report single crystal preparation, resistivity, and nuclear quadrupole
      resonance (NQR) measurements for new pressure-induced superconductor CrAs. In the
      first part, we present the difference between crystals made by different thermal
      sequences and methods, and show the sample dependence of superconductivity in
      CrAs. In the latter part, we show NQR data focusing the microscopic electronic
      state at the phase boundary between the helimagnetic and the paramagnetic phases.
      They suggest strongly that a quantum critical point is absent on the pressure
      temperature phase diagram of CrAs, because of the strong first-order character of
      the magnetic transition; however, the spin fluctuations are observed in the
      paramagnetic phase. The close relationship between the spin fluctuations and
      superconductivity can be seen even in the vicinity of the first-order magnetic
      transition in CrAs.

PMID- 28430105
TI  - Switching of metabolic programs in response to light availability is an essential
      function of the cyanobacterial circadian output pathway.
AB  - The transcription factor RpaA is the master regulator of circadian transcription
      in cyanobacteria, driving genome-wide oscillations in mRNA abundance. Deletion of
      rpaA has no effect on viability in constant light conditions, but renders cells
      inviable in cycling conditions when light and dark periods alternate. We
      investigated the mechanisms underlying this viability defect, and demonstrate
      that the rpaA- strain cannot maintain appropriate energy status at night, does
      not accumulate carbon reserves during the day, and is defective in transcription
      of genes crucial for utilization of carbohydrate stores at night. Reconstruction
      of carbon utilization pathways combined with provision of an external carbon
      source restores energy charge and viability of the rpaA- strain in light/dark
      cycling conditions. Our observations highlight how a circadian output pathway
      controls and temporally coordinates essential pathways in carbon metabolism to
      maximize fitness of cells facing periodic energy limitations.

PMID- 28430108
TI  - A network physiology approach to the assessment of the link between sinoatrial
      and ventricular cardiac controls.
AB  - OBJECTIVE: A network physiology approach to evaluate the strength of the directed
      interactions among cardiac controls at sinoatrial and ventricular levels and
      respiration (R) is proposed. APPROACH: The network is composed of three nodes
      (i.e. sinoatrial and ventricular cardiac controls and R) and their activity is
      exemplified by the variability of heart period (HP), the variability of the
      duration of the electrical activity of the heart approximated as the temporal
      distance between Q-wave onset and T-wave end or apex (i.e. QTe or QTa) and
      thoracic movements respectively. Model-based transfer entropy provided the
      estimate of the strength of the causal link from the source to the destination
      conditioned on the remaining node activity. The interactions were monitored in 15
      healthy subjects aged from 24 to 54 years (9 males). Increasing levels of
      sympathetic activity were induced by graded head-up tilt with table inclination
      of 0, 15, 30, 45, 60, 75 degrees . MAIN RESULTS: We found that: (i) the strength
      of the causal link from HP to QTe gradually decreases with tilt table angle,
      while that in the reverse direction is weak, even though significant, and
      constant; (ii) the action of R on HP is stronger than that from R to QTe; (iii)
      the strength of the relation from R to HP is weakly related to tilt table
      inclination, while that from R to QTe does not depend on it; (iv) while QTe
      cannot affect R, a weak causal dependence of R on HP is detected; (v) the network
      computed over QTa is qualitatively similar to that over QTe, even though the
      strength of the causal relations might be different. SIGNIFICANCE: The proposed
      network physiology approach provides a comprehensive picture of the directed
      links among relevant cardiac regulatory mechanisms and their evolution with
      sympathetic tone usable to identify pathological conditions.

PMID- 28430109
TI  - Acquisition of electrocardiogram signals during magnetic resonance imaging.
AB  - The recording of the electrocardiogram (ECG) during magnetic resonance imaging
      (MRI) acquisition is of great interest and importance. Firstly, MRI acquisition
      is a relatively slow process, which therefore complicates the imaging of moving
      organs. Cardiac MRI requires the development of strategies for acquiring high
      quality images, which is mainly achieved by synchronising the image acquisition
      with a specific time during the cardiac cycle. The ECG is used to monitor the
      heart's activity, and the detection of the largest and steepest peak in the
      cardiac cycle (the QRS complex) triggers the acquisition of slices of the k
      space. Secondly, patients undergoing an MRI examination need to be monitored for
      safety during the procedure, and therefore ECG signals are used to track their
      cardiovascular state in real time. However, there are significant barriers to the
      accurate observation and processing of the ECG during MRI acquisition. In
      particular, the flow of charged blood particles through the large applied
      magnetic field leads to an extra current source, known as the magnetohdrodymanic
      (MHD) effect. This review article discusses these barriers and state-of-the-art
      solutions. An overview of the relevant technology including hardware and
      applications are described. The development of new software tools for the
      processing of the ECG signals acquired during MRI is also detailed. These
      developments include the design of specific QRS detection algorithms, which are
      able to distinguish QRS complexes from the MHD effect but also the gradient
      artefacts. Different techniques for the suppression of the gradient artefacts are
      also presented as well as the most challenging problem to-date-the problem of
      separating the MHD effect from the ECG. The article concludes by summarising the
      advantages of using ECG signals during MRI, but also presents the current
      limitations of modern analysis techniques in this domain. The most promising
      avenues of research are also discussed and suggestions for new methodological
      analyses for the development of this field are given.

PMID- 28430110
TI  - Viscosity of a sheared correlated (near-critical) model fluid in confinement.
AB  - Second-order phase transitions are characterized by a divergence of the spatial
      correlation length of the order parameter fluctuations. For confined systems,
      this is known to lead to remarkable equilibrium physical phenomena, including
      finite-size effects and critical Casimir forces. We explore here some non
      equilibrium aspects of these effects in the stationary state resulting from the
      action of external forces: by analyzing a model of a correlated fluid under
      shear, spatially confined by two parallel plates, we study the resulting
      viscosity within the setting of (Gaussian) Landau-Ginzburg theory. Specifically,
      we introduce a model in which the hydrodynamic velocity field (obeying the Stokes
      equation) is coupled to an order parameter with dissipative dynamics. The well
      known Green-Kubo relation for bulk systems is generalized for confined systems.
      This is shown to result in a non-local Stokes equation for the fluid flow, due to
      the correlated fluctuations. The resulting effective shear viscosity shows
      universal as well as non-universal contributions, which we study in detail. In
      particular, the deviation from the bulk behavior is universal, depending on the
      ratio of the correlation length and the film thickness L. In addition, at the
      critical point the viscosity is proportional to [Formula: see text], where
      [Formula: see text] is a dynamic length scale. These findings are expected to be
      experimentally observable, especially for systems where the bulk viscosity is
      affected by critical fluctuations.

PMID- 28430111
TI  - Wavepacket dynamics and the multi-configurational time-dependent Hartree
      approach.
AB  - Multi-configurational time-dependent Hartree (MCTDH) based approaches are
      efficient, accurate, and versatile methods for high-dimensional quantum dynamics
      simulations. Applications range from detailed investigations of polyatomic
      reaction processes in the gas phase to high-dimensional simulations studying the
      dynamics of condensed phase systems described by typical solid state physics
      model Hamiltonians. The present article presents an overview of the different
      areas of application and provides a comprehensive review of the underlying
      theory. The concepts and guiding ideas underlying the MCTDH approach and its
      multi-mode and multi-layer extensions are discussed in detail. The general
      structure of the equations of motion is highlighted. The representation of the
      Hamiltonian and the correlated discrete variable representation (CDVR), which
      provides an efficient multi-dimensional quadrature in MCTDH calculations, are
      discussed. Methods which facilitate the calculation of eigenstates, the
      evaluation of correlation functions, and the efficient representation of thermal
      ensembles in MCTDH calculations are described. Different schemes for the
      treatment of indistinguishable particles in MCTDH calculations and recent
      developments towards a unified multi-layer MCTDH theory for systems including
      bosons and fermions are discussed.

PMID- 28430112
TI  - Malignant endometriosis of the abdominal wall.
AB  - : Endometriosis is a disease represented by the presence of extra uterine
      endometrial tissue. It is a rare condition, and malignant transformation is
      seldom. We report a case with clear cell adenocarcinoma oncogenesis on abdominal
      wall scar that appeared after years of a caesarian section. After diagnosis,
      surgical treatment was performed twice, due to the fact that the margins were
      infiltrated with tumor cells, with replacement of the defect with a polypropylene
      mesh. The patient was cured and discharged with a favorable prognostic. To the
      best of our knowledge, there are few reported cases of clear cell adenocarcinoma
      arising from abdominal wall endometriosis. It is a rare condition that appears
      mostly after abdominal surgical interventions that clinicians must be aware. KEY
      WORDS: Abdominal wall, Endometriosis, Cesarean section, Clear cell
      adenocarcinoma, Malignant transformation.

PMID- 28430113
TI  - Should physicians instead of industry representatives be the main actor of
      cardiac implantable electronic device follow-up? (Super Follow-up).
AB  - OBJECTIVE: This retrospective study sought to research the adequacy of the follow
      up and optimization of cardiac implantable electronic devices (CIEDs) performed
      by industry representatives. METHODS: A total of 403 consecutive patients (35%
      females; median age, 67 years; age range 18-97 years) with either pacemakers
      (n=246), implantable cardioverter-defibrillators (ICDs), (n=117) or cardiac
      resynchronization therapy with defibrillator (CRT-D) (n=40) applied to our
      hospital's outpatient pacemaker clinic for follow-up. These patients had been
      followed up by industry representatives alone until September 2013 and then by a
      cardiologist who is dealing with cardiac electrophysiology and has a knowledge of
      CIED follow-up. RESULTS: It was ascertained that 117 (47.6%) of 246 patients with
      pacemakers had a programming error. Forty-three (36.8%) of 117 patients were
      symptomatic, and after reprogramming, all symptoms diminished partially or
      completely during the follow-up. Moreover, 30 (25.6%) of 117 patients with ICDs
      had a programming error. Furthermore, 6 (15%) of 40 patients with CRT-Ds had a
      programming error. To conclude, when all patients with CIEDs were assessed
      together, it was ascertained that 153 (38%) of 403 patients had programming
      errors. CONCLUSION: The prevalence of inappropriate programming of CIEDs by
      industry representatives was quite higher than expected. Therefore, our study
      strongly demonstrates that CIED follow-up should not be allowed to be performed
      entirely by manufacturers' representatives alone.

PMID- 28430114
TI  - Urban and rural differences in hypertension risk factors in Turkey.
AB  - OBJECTIVE: Existing literature shows considerable regional differences in terms
      of hypertension (HT) prevalence in Turkey. The purpose of this study was to
      analyze some of the known HT risk factors contributing to the variations between
      urban and rural areas of Turkey in HT development. METHODS: We used data from the
      2011 Chronic Diseases and Risk Factors Survey that was conducted by the Turkish
      Ministry of Health on a representative sample of the Turkish adult population
      aged 20 years or more (n=16.227). HT was defined as having at least one of the
      following: a mean systolic/diastolic blood pressure of at least 140/90 mm Hg, a
      previously diagnosed disease, or use of antihypertensive medication. Stepwise
      multiple logistic regression analysis was used to estimate HT risk factors in
      urban and rural settings. RESULTS: Although the HT prevalence was higher in rural
      areas (28.4%) than in urban areas (23.9%), in this study, urbanization was found
      to be a contributing factor in multivariate regression analysis. Furthermore,
      separate regressions for urban and rural settings revealed that age, obesity,
      diabetes, hyperlipidemia, and smoking were independently and positively
      associated (p<0.05) with HT in both settings, while marital status, employment
      type, mental health, and lifestyle patterns; nutritional habits; and amount of
      physical activity and sedentary time (p<0.05) were risk indicators in urban areas
      only. CONCLUSION: The findings of our study demonstrate that contributory factors
      show some variations between urban and rural settings, and on gender within each
      setting. Taking into account the variations between urban and rural areas in HT
      development may provide greater insight into the design of prevention strategies.

PMID- 28430115
TI  - A systematic review of 3-D printing in cardiovascular and cerebrovascular
      diseases.
AB  - OBJECTIVE: The application of 3-D printing has been increasingly used in
      medicine, with research showing many applications in cardiovascular disease. This
      systematic review analyzes those studies published about the applications of 3-D
      printed, patient-specific models in cardiovascular and cerebrovascular diseases.
      METHODS: A search of PubMed/Medline and Scopus databases was performed to
      identify studies investigating the 3-D printing in cardiovascular and
      cerebrovascular diseases. Only studies based on patient's medical images were
      eligible for review, while reports on in vitro phantom or review articles were
      excluded. RESULTS: A total of 48 studies met selection criteria for inclusion in
      the review. A range of patient-specific 3-D printed models of different
      cardiovascular and cerebrovascular diseases were generated in these studies with
      most of them being developed using cardiac CT and MRI data, less commonly with 3
      D invasive angiographic or echocardiographic images. The review of these studies
      showed high accuracy of 3-D printed, patient-specific models to represent complex
      anatomy of the cardiovascular and cerebrovascular system and depict various
      abnormalities, especially congenital heart diseases and valvular pathologies.
      Further, 3-D printing can serve as a useful education tool for both parents and
      clinicians, and a valuable tool for pre-surgical planning and simulation.
      CONCLUSION: This systematic review shows that 3-D printed models based on medical
      imaging modalities can accurately replicate complex anatomical structures and
      pathologies of the cardiovascular and cerebrovascular system. 3-D printing is a
      useful tool for both education and surgical planning in these diseases.

PMID- 28430116
TI  - Ghrelin expression and significance in 92 patients with atrial fibrillation.
AB  - OBJECTIVE: Ghrelin is a polypeptide that is closely associated with many
      cardiovascular diseases, such as hypertension, atherosclerosis, and heart
      failure. This article aims to understand the expression of ghrelin in patients
      with atrial fibrillation (AF). METHODS: A total of 182 patients with non-valvular
      heart diseases were recruited, among whom 92 had AF and 90 had sinus arrhythmia
      (SA). The serum ghrelin amount was tested by the ELASA method. Moreover, blood
      sugar, lipids, liver function, and renal function were tested. All recruited
      patients underwent echocardiographic examination following admission. Three
      cardiac cycles were observed under continuous exhalation. The left atrial
      diameter (LAD) and the left ventricular ejection fraction (LVEF) were measured
      and averaged. Patients with AF received conventional treatment, and the
      aforementioned parameters were re-measured after 8 weeks. The results were
      statistically analyzed. RESULTS: The serum ghrelin level in the patients in the
      AF group (199.55+/-79.59 pg/mL) was lower than that in the patients in the SA
      group (313.89+/-71.13 pg/mL, p<0.01), whereas the serum ghrelin level in those in
      the paroxysmal AF group (224.44+/-72.33 pg/mL) was higher than that in those in
      the persistent AF group (176.00+/-79.88 pg/mL, p<0.01). There was a positive
      correlation between the serum ghrelin level and LVEF in the patients in the AF
      group (r=0.704, p=0.046). After treatment, the serum ghrelin level and LVEF in
      the patients in the AF group significantly increased, whereas LAD decreased.
      CONCLUSION: The serum ghrelin level in patients with AF was reduced, and after
      treatment, it significantly increased. There was a positive correlation between
      the serum ghrelin level and LVEF in the patients in the AF group.

PMID- 28430117
TI  - Fluvastatin therapy could not decrease progression of paroxysmal atrial
      fibrillation in non-valvular disease patients.
AB  - OBJECTIVE: This study aimed to evaluate whether fluvastatin therapy could
      decrease the probability of atrial fibrillation (AF) progression from paroxysmal
      AF to permanent AF and decrease the recurrence frequency of AF. METHODS: Analyses
      were performed using two-tailed Student's t test or Mann-Whitney U tests.
      Categorical variables were compared with the chi2 statistics or Fisher's exact
      test. Patients with paroxysmal AF were randomized case-control, prospective into
      either the fluvastatin group (n=61) or control group (n=57). Patients were
      followed up for 24 months. The primary endpoint event was paroxysmal AF that
      progressed to permanent AF. Secondary endpoints were AF recurrence, cardiac
      dysfunction, stroke, or death. RESULTS: There were no differences in AF
      progression (fluvastatin group, 8.19% vs. control group, 12.51%; p>0.05) and
      stroke (fluvastatin group. 6.55% vs. CONTROL GROUP: 8.77%; p>0.05). Patients in
      the fluvastatin group had a lower rate of AF recurrence (fluvastatin group,
      24.59% vs. control group, 49.12%; p<0.05) and a lower rate of cardiac dysfunction
      (fluvastatin group, 6.55% vs. control group, 19.29%; p<0.05). Death did not occur
      in both the groups. After 1 week of fluvastatin therapy, C-reactive protein (CRP)
      and homocysteine (HCY) levels were lower in the fluvastatin group than in the
      control group. At 24 months of follow-up, CRP and HCY levels remained lower in
      the fluvastatin group than in the control group. The number of endothelial
      progenitor cells (EPCs) increased in the fluvastatin group compared with that in
      the control group (fluvastatin group, 72.27+/-12.49 counts/105 vs. control group,
      57.45+/-8.24 counts/105, p=0.001). CONCLUSION: Fluvastatin therapy could not
      decrease AF progression. However, it could decrease the recurrence frequency of
      paroxysmal AF and cardiac dysfunction. This may occur because of depressing
      inflammation and improving circulating EPCs.

PMID- 28430118
TI  - Testing the Capacity of a Multi-Nutrient Profiling System to Guide Food and
      Beverage Reformulation: Results from Five National Food Composition Databases.
AB  - Nutrient profiling ranks foods based on their nutrient composition, with
      applications in multiple aspects of food policy. We tested the capacity of a
      category-specific model developed for product reformulation to improve the
      average nutrient content of foods, using five national food composition datasets
      (UK, US, China, Brazil, France). Products (n = 7183) were split into 35
      categories based on the Nestle Nutritional Profiling Systems (NNPS) and were then
      classified as NNPS 'Pass' if all nutrient targets were met (energy (E), total fat
      (TF), saturated fat (SFA), sodium (Na), added sugars (AS), protein, calcium). In
      a modelling scenario, all NNPS Fail products were 'reformulated' to meet NNPS
      standards. Overall, a third (36%) of all products achieved the NNPS standard/pass
      (inter-country and inter-category range: 32%-40%; 5%-72%, respectively), with
      most products requiring reformulation in two or more nutrients. The most common
      nutrients to require reformulation were SFA (22%-44%) and TF (23%-42%). Modelled
      compliance with NNPS standards could reduce the average content of SFA, Na and AS
      (10%, 8% and 6%, respectively) at the food supply level. Despite the good
      potential to stimulate reformulation across the five countries, the study
      highlights the need for better data quality and granularity of food composition
      databases.

PMID- 28430119
TI  - Influence of Wind Speed on RGB-D Images in Tree Plantations.
AB  - Weather conditions can affect sensors' readings when sampling outdoors. Although
      sensors are usually set up covering a wide range of conditions, their operational
      range must be established. In recent years, depth cameras have been shown as a
      promising tool for plant phenotyping and other related uses. However, the use of
      these devices is still challenged by prevailing field conditions. Although the
      influence of lighting conditions on the performance of these cameras has already
      been established, the effect of wind is still unknown. This study establishes the
      associated errors when modeling some tree characteristics at different wind
      speeds. A system using a Kinect v2 sensor and a custom software was tested from
      null wind speed up to 10 m.s-1. Two tree species with contrasting architecture,
      poplars and plums, were used as model plants. The results showed different
      responses depending on tree species and wind speed. Estimations of Leaf Area (LA)
      and tree volume were generally more consistent at high wind speeds in plum trees.
      Poplars were particularly affected by wind speeds higher than 5 m.s-1. On the
      contrary, height measurements were more consistent for poplars than for plum
      trees. These results show that the use of depth cameras for tree characterization
      must take into consideration wind conditions in the field. In general, 5 m.s-1
      (18 km.h-1) could be established as a conservative limit for good estimations.

PMID- 28430120
TI  - Autonomous Multi-Robot Search for a Hazardous Source in a Turbulent Environment.
AB  - Finding the source of an accidental or deliberate release of a toxic substance
      into the atmosphere is of great importance for national security. The paper
      presents a search algorithm for turbulent environments which falls into the class
      of cognitive (infotaxi) algorithms. Bayesian estimation of the source parameter
      vector is carried out using the Rao-Blackwell dimension-reduction method, while
      the robots are controlled autonomously to move in a scalable formation.
      Estimation and control are carried out in a centralised replicated fusion
      architecture assuming all-to-all communication. The paper presents a
      comprehensive numerical analysis of the proposed algorithm, including the search
      time and displacement statistics.

PMID- 28430121
TI  - Synthesis, Characterization and Enhanced Sensing Properties of a NiO/ZnO p-n
      Junctions Sensor for the SF6 Decomposition Byproducts SO2, SO2F2, and SOF2.
AB  - The detection of partial discharge and analysis of the composition and content of
      sulfur hexafluoride SF6 gas components are important to evaluate the operating
      state and insulation level of gas-insulated switchgear (GIS) equipment. This
      paper reported a novel sensing material made of pure ZnO and NiO-decorated ZnO
      nanoflowers which were synthesized by a facile and environment friendly
      hydrothermal process for the detection of SF6 decomposition byproducts. X-ray
      diffraction (XRD), field emission scanning electron microscopy (FESEM),
      transmission electron microscopy (TEM), high resolution transmission electron
      microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS) and X-ray
      photoelectron spectroscopy (XPS) were used to characterize the structural and
      morphological properties of the prepared gas-sensitive materials. Planar-type
      chemical gas sensors were fabricated and their gas sensing performances toward
      the SF6 decomposition byproducts SO2, SO2F2, and SOF2 were systemically
      investigated. Interestingly, the sensing behaviors of the fabricated ZnO
      nanoflowers-based sensor to SO2, SO2F2, and SOF2 gases can be obviously enhanced
      in terms of lower optimal operating temperature, higher gas response and shorter
      response-recovery time by introducing NiO. Finally, a possible gas sensing
      mechanism for the formation of the p-n junctions between NiO and ZnO is proposed
      to explain the enhanced gas response. All results demonstrate a promising
      approach to fabricate high-performance gas sensors to detect SF6 decomposition
      byproducts.

PMID- 28430122
TI  - A Comprehensive Diverse '-omics' Approach to Better Understanding the Molecular
      Pathomechanisms of Down Syndrome.
AB  - Diverse '-omics' technologies permit the comprehensive quantitative profiling of
      a variety of biological molecules. Comparative '-omics' analyses, such as
      transcriptomics and proteomics, are powerful and useful tools for unraveling the
      molecular pathomechanisms of various diseases. As enhanced oxidative stress has
      been demonstrated in humans and mice with Down syndrome (DS), a redox proteomic
      analysis is useful for understanding how enhanced oxidative stress aggravates the
      state of individuals with oxidative stress-related disorders. In this review, '
      omics' analyses in humans with DS and mouse models of DS are summarized, and the
      molecular dissection of this syndrome is discussed.

PMID- 28430123
TI  - Functional Analysis of the rs774872314, rs116171003, rs200231898 and rs201107751
      Polymorphisms in the Human RORgammaT Gene Promoter Region.
AB  - RAR-related orphan receptor gamma RORgammaT, a tissue-specific isoform of the
      RORC gene, plays a critical role in the development of naive CD4+ cells into
      fully differentiated Th17 lymphocytes. Th17 lymphocytes are part of the host
      defense against numerous pathogens and are also involved in the pathogenesis of
      inflammatory diseases, including autoimmune disorders. In this study, we
      functionally examined four naturally occurring polymorphisms located within one
      of the previously identified GC-boxes in the promoter region of the gene. The
      single nucleotide polymorphisms (SNPs) rs774872314, rs116171003 and rs201107751
      negatively influenced the activity of the RORgammaT promoter in a gene reporter
      system and eliminated or reduced Sp1 and Sp2 transcription factor binding, as
      evidenced by the electrophoretic mobility shift assay (EMSA) technique.
      Furthermore, we investigated the frequency of these SNPs in the Polish population
      and observed the presence of rs116171003 at a frequency of 3.42%. Thus, our
      results suggest that polymorphisms within the RORgammaT promoter occurring at
      significant rates in populations affect promoter activity. This might have
      phenotypic effects in immune systems, which is potentially significant for
      implicating pathogenetic mechanisms under certain pathological conditions, such
      as autoimmune diseases and/or primary immunodeficiencies (e.g., immunoglobulin E
      (IgE) syndrome).

PMID- 28430125
TI  - Erratum: Tingting Lian, et al. Identification of Site-Specific Stroke Biomarker
      Candidates by Laser Capture Microdissection and Labeled Reference Peptide. Int.
      J. Mol. Sci. 2015, 16, 13427-13441.
AB  - n/a.

PMID- 28430124
TI  - Association between Serum Selenium Concentrations and Levels of Proinflammatory
      and Profibrotic Cytokines-Interleukin-6 and Growth Differentiation Factor-15, in
      Patients with Alcoholic Liver Cirrhosis.
AB  - According to some authors, serum selenium levels are strongly associated with the
      severity of liver diseases, including liver cirrhosis. The aim of this study was
      to determine the relationship between the concentration of selenium and pro
      inflammatory and profibrotic cytokines-interleukin-6 (IL-6) and growth
      differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis.
      The parameters studied were determined in the serum of 99 patients with alcoholic
      liver cirrhosis divided based on the severity of disease according to the Child
      Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium
      concentration was statistically lower, whereas serum IL-6 and GDF-15
      concentrations were higher than those in the control group. Moreover, the
      concentration of selenium negatively correlated with the levels of GDF-15 and IL
      6. The above results may indicate a role of selenium deficiency in the
      pathogenesis and progression of alcoholic liver disease.

PMID- 28430126
TI  - Accurate Ambient Noise Assessment Using Smartphones.
AB  - Nowadays, smartphones have become ubiquitous and one of the main communication
      resources for human beings. Their widespread adoption was due to the huge
      technological progress and to the development of multiple useful applications.
      Their characteristics have also experienced a substantial improvement as they now
      integrate multiple sensors able to convert the smartphone into a flexible and
      multi-purpose sensing unit. The combined use of multiple smartphones endowed with
      several types of sensors gives the possibility to monitor a certain area with
      fine spatial and temporal granularity, a procedure typically known as
      crowdsensing. In this paper, we propose using smartphones as environmental noise
      sensing units. For this purpose, we focus our study on the sound capture and
      processing procedure, analyzing the impact of different noise calculation
      algorithms, as well as in determining their accuracy when compared to a
      professional noise measurement unit. We analyze different candidate algorithms
      using different types of smartphones, and we study the most adequate time period
      and sampling strategy to optimize the data-gathering process. In addition, we
      perform an experimental study comparing our approach with the results obtained
      using a professional device. Experimental results show that, if the smartphone
      application is well tuned, it is possible to measure noise levels with a accuracy
      degree comparable to professional devices for the entire dynamic range typically
      supported by microphones embedded in smartphones, i.e., 35-95 dB.

PMID- 28430127
TI  - Image-Guided Laparoscopic Surgical Tool (IGLaST) Based on the Optical Frequency
      Domain Imaging (OFDI) to Prevent Bleeding.
AB  - We present an image-guided laparoscopic surgical tool (IGLaST) to prevent
      bleeding. By applying optical frequency domain imaging (OFDI) to a specially
      designed laparoscopic surgical tool, the inside of fatty tissue can be observed
      before a resection, and the presence and size of blood vessels can be recognized.
      The optical sensing module on the IGLaST head has a diameter of less than 390 um
      and is moved back and forth by a linear servo actuator in the IGLaST body. We
      proved the feasibility of IGLaST by in vivo imaging inside the fatty tissue of a
      porcine model. A blood vessel with a diameter of about 2.2 mm was clearly
      observed. Our proposed scheme can contribute to safe surgery without bleeding by
      monitoring vessels inside the tissue and can be further expanded to detect
      invisible nerves of the laparoscopic thyroid during prostate gland surgery.

PMID- 28430128
TI  - Environmental Tobacco Smoke Exposure and Smoke-Free Rules in Homes among Socially
      Disadvantaged Populations in Poland.
AB  - This study aims to examine the prevalence of exposure to environmental tobacco
      smoke (ETS) in homes among socially-disadvantaged populations in Poland, along
      with the prevalence and correlates of voluntary implementation of smoke-free home
      rules. Data concerning 1617 respondents from a cross-sectional study completed in
      the Piotrkowski District were used, which was part of the "Reducing Social
      Inequalities in Health" program. Overall, 19.4% of the respondents declared
      exposure to ETS at home. In the non-smokers group, 15.5%, including 6.6% males
      and 18.3% females, were exposed to ETS in their place of residence (p < 0.0001).
      Complete smoke-free rules were adopted by 22.1% of the study participants. Two
      factors, smoker status and lack of ETS-associated health risk awareness, were
      found to be significantly associated with no adoption of total smoking bans at
      home. Socially-disadvantaged non-smokers, especially females from rural areas in
      Poland, still constitute a large population exposed to ETS in their homes-a
      challenge from the perspective of public health. Focused efforts are required to
      address social norms around exposing others to ETS.

PMID- 28430129
TI  - Curcumin Inhibits Apoptosis of Chondrocytes through Activation ERK1/2 Signaling
      Pathways Induced Autophagy.
AB  - Osteoarthritis (OA) is an inflammatory disease of load-bearing synovial joints
      that is currently treated with drugs that exhibit numerous side effects and are
      only temporarily effective in treating pain, the main symptom of the disease.
      Consequently, there is an acute need for novel, safe, and more effective
      chemotherapeutic agents for the treatment of osteoarthritis and related arthritic
      diseases. Curcumin, the principal curcuminoid and the most active component in
      turmeric, is a biologically active phytochemical. Evidence from several recent in
      vitro studies suggests that curcumin may exert a chondroprotective effect through
      actions such as anti-inflammatory, anti-oxidative stress, and anti-catabolic
      activity that are critical for mitigating OA disease pathogenesis and symptoms.
      In the present study, we investigated the protective mechanisms of curcumin on
      interleukin 1beta (IL-1beta)-stimulated primary chondrocytes in vitro. The
      treatment of interleukin (IL)-1beta significantly reduces the cell viability of
      chondrocytes in dose and time dependent manners. Co-treatment of curcumin with IL
      1beta significantly decreased the growth inhibition. We observed that curcumin
      inhibited IL-1beta-induced apoptosis and caspase-3 activation in chondrocytes.
      Curcumin can increase the expression of phosphorylated extracellular signal
      regulated kinases 1/2 (ERK1/2), autophagy marker light chain 3 (LC3)-II, and
      Beclin-1 in chondrocytes. The expression of autophagy markers could be decreased
      when the chondrocytes were incubated with ERK1/2 inhibitor U0126. Our results
      suggest that curcumin suppresses apoptosis and inflammatory signaling through its
      actions on the ERK1/2-induced autophagy in chondrocytes. We propose that curcumin
      should be explored further for the prophylactic treatment of osteoarthritis in
      humans and companion animals.

PMID- 28430130
TI  - Timp1 Promotes Cell Survival by Activating the PDK1 Signaling Pathway in
      Melanoma.
AB  - High TIMP1 expression is associated with poor prognosis in melanoma, where it can
      bind to CD63 and beta1 integrin, inducing PI3-kinase pathway and cell survival.
      Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), generated under
      phosphatidylinositol-3-kinase (PI3K) activation, enables the recruitment and
      activation of protein kinase B (PKB/AKT) and phosphoinositide-dependent kinase 1
      (PDK1) at the membrane, resulting in the phosphorylation of a host of other
      proteins. Using a melanoma progression model, we evaluated the impact of Timp1
      and AKT silencing, as well as PI3K, PDK1, and protein kinase C (PKC) inhibitors
      on aggressiveness characteristics. Timp1 downregulation resulted in decreased
      anoikis resistance, clonogenicity, dacarbazine resistance, and in vivo tumor
      growth and lung colonization. In metastatic cells, pAKTThr308 is highly
      expressed, contributing to anoikis resistance. We showed that PDK1Ser241 and
      PKCbetaIISer660 are activated by Timp1 in different stages of melanoma
      progression, contributing to colony formation and anoikis resistance. Moreover,
      simultaneous inhibition of Timp1 and AKT in metastatic cells resulted in more
      effective anoikis inhibition. Our findings demonstrate that Timp1 promotes cell
      survival with the participation of PDK1 and PKC in melanoma. In addition, Timp1
      and AKT act synergistically to confer anoikis resistance in advanced tumor
      stages. This study brings new insights about the mechanisms by which Timp1
      promotes cell survival in melanoma, and points to novel perspectives for
      therapeutic approaches.

PMID- 28430131
TI  - Evaluation of Tanshinone IIA Developmental Toxicity in Zebrafish Embryos.
AB  - Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza
      Bunge, a traditional Chinese medicine. Although Salvia miltiorrhiza has been
      applied for many years, the toxicity of the mono-constituent of Salvia
      miltiorrhiza, tanshinone IIA, is still understudied. This study evaluated the
      cardiotoxicity and developmental malformations of Tan-IIA by using zebrafish
      normal embryos and dechorionated embryos. After treatment with Tan-IIA in
      different concentrations for four-day periods, obvious pericardial edema, spinal
      curvature, and even missing tails were observed in zebrafish embryos. The LC50
      values in the dechorionated embryo group at 72 h post-fertilization (hpf) and 96
      hpf were 18.5 MUM and 12.8 MUM, respectively, and the teratogenicity was
      manifested at a concentration of about 1 uM. The main endpoints of teratogenicity
      were scoliosis, malformation of tail, and pericardium edema. Our findings
      displayed the potential cardiotoxicity and severe impact on the abnormal
      development of Tan-IIA in zebrafish embryo at high concentrations, which may help
      avoid the risk of its clinical application.

PMID- 28430132
TI  - Celestial Object Imaging Model and Parameter Optimization for an Optical
      Navigation Sensor Based on the Well Capacity Adjusting Scheme.
AB  - The simultaneous extraction of optical navigation measurements from a target
      celestial body and star images is essential for autonomous optical navigation.
      Generally, a single optical navigation sensor cannot simultaneously image the
      target celestial body and stars well-exposed because their irradiance difference
      is generally large. Multi-sensor integration or complex image processing
      algorithms are commonly utilized to solve the said problem. This study analyzes
      and demonstrates the feasibility of simultaneously imaging the target celestial
      body and stars well-exposed within a single exposure through a single field of
      view (FOV) optical navigation sensor using the well capacity adjusting (WCA)
      scheme. First, the irradiance characteristics of the celestial body are analyzed.
      Then, the celestial body edge model and star spot imaging model are established
      when the WCA scheme is applied. Furthermore, the effect of exposure parameters on
      the accuracy of star centroiding and edge extraction is analyzed using the
      proposed model. Optimal exposure parameters are also derived by conducting Monte
      Carlo simulation to obtain the best performance of the navigation sensor.
      Finally, laboratorial and night sky experiments are performed to validate the
      correctness of the proposed model and optimal exposure parameters.

PMID- 28430133
TI  - Nuclear Molecular Imaging Strategies in Immune Checkpoint Inhibitor Therapy.
AB  - Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed
      for the treatment of cancer. ICT inhibits pathways known to downregulate the
      innate immune response to cancer cells. These drugs have been shown to be
      effective in the treatment of a variety of cancers, including metastatic melanoma
      and lung cancer. Challenges in response evaluation of patients in ICT have risen
      as immune related side effects and immune cell infiltration may be confused with
      progressive disease. Furthermore, the timing of the evaluation scan may be
      challenged by relatively slow responses. To overcome this, new response criteria
      for evaluating these patients with morphologic imaging have been proposed. The
      aim of this paper is to review and discuss the current evidence for the use of
      molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer
      Tomography) with 18F-Fluorodeoxyglucoes (FDG) as an alternative imaging method
      for monitoring patients undergoing ICT. Following the currently available
      evidence, this review will primarily focus on patients with malignant melanoma.

PMID- 28430134
TI  - On the Morphology of Group II Metal Fluoride Nanocrystals at Finite Temperature
      and Partial Pressure of HF.
AB  - We have investigated the bulk and surface properties of the group II metal
      fluorides CaF 2 , SrF 2 and BaF 2 using periodic density functional theory (DFT)
      calculations and surface thermodynamics. Our bulk results show that the best
      agreement with experiment is achieved with the B3LYP and PBE functionals. We
      determined the relative importance of the low index surfaces in vacuum and found
      that an fluoride microcrystal exposes only the (111) surface in which the
      undercoordinated cations are sevenfold coordinated. With methods of ab initio
      surface thermodynamics, we analyzed the stability of different surfaces under
      hydrogen fluoride (HF) pressure and determined the presumable shape of the
      crystals with respect to different HF concentrations and temperatures. In the
      case of CaF 2 and SrF 2 , the calculated shapes of the crystals agree well with
      TEM images of fluorolytic sol-gel synthesized nanocrystals at room temperature
      and high HF concentration.

PMID- 28430135
TI  - A Homochiral Multifunctional Metal-Organic Framework with Rod-Shaped Secondary
      Building Units.
AB  - A new homochiral multifunctional metal-organic framework, [Zn2(CTBA)2.H2O] (JUC
      112), was synthesized under solvothermal conditions, through the design of chiral
      ligand 4-(3-carboxy-2,2,3-trimethylcyclopentanecarboxamido) benzoic acid (H2CTBA)
      based on camphoric acid as building block. The crystal structure of the new
      material is a 2-dimensional (2D) chiral layer packed with infinite rod-shaped
      secondary building units (SBUs). The homochiral framework was identified by
      circular dichroism (CD) spectrum. Thermogravimetric measurement indicates its
      high thermal stability up to 450  degrees C. In addition, JUC-112 exhibits the
      capability of separating water from alcohols, second-order nonlinear optical
      effect, and photoluminescence.

PMID- 28430136
TI  - Therapeutic Effect of Low Doses of Acenocoumarol in the Course of
      Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.
AB  - : Intravascular activation of coagulation is observed in acute pancreatitis and
      is related to the severity of this inflammation. The aim of our study was to
      evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis
      induced in male rats by pancreatic ischemia followed by reperfusion.
      Acenocoumarol at a dose of 50, 100, or 150 ug/kg/dose was administered
      intragastrically once a day, starting the first dose 24 h after the initiation of
      pancreatic reperfusion. RESULTS: Histological examination showed that treatment
      with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats
      with pancreatitis. Moreover, the administration of acenocoumarol decreased
      pancreatic inflammatory infiltration and vacuolization of pancreatic acinar
      cells. These findings were accompanied with a reduction in the serum activity of
      lipase and amylase, concentration of interleukin-1beta, and plasma d-Dimer
      concentration. Moreover, the administration of acenocoumarol improved pancreatic
      blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150
      ug/kg/dose was the most effective in the treatment of early phase acute
      pancreatitis. However later, acenocoumarol given at the highest dose failed to
      exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still
      effective in the treatment of acute pancreatitis. CONCLUSION: Treatment with
      acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute
      pancreatitis in rats.

PMID- 28430137
TI  - Parent, partner, co-parent or partnership? The need for clarity as family systems
      thinking takes hold in the quest to motivate behavioural change.
AB  - Research is increasingly pointing to the importance of extending the focus of
      childhood obesity intervention to include fathers, fathering figures, and other
      members of a child's primary parenting network. Advances in communication
      technology are now making it possible to achieve this aim, within current
      resources, using modalities such text messaging, web-based resources and apps
      that extend intervention to parents not in attendance at face to face
      interactions. However, published research is often unclear as to which parent/s
      they targeted or engaged with, whether interventions planned to influence
      behaviours and capabilities across family systems, and how this can be achieved.
      As childhood obesity research employing information technology to engage with
      family systems takes hold it is becoming important for researchers clearly
      describe who they engage with, what they hope to achieve with them, and the
      pathways of influence that they aim to activate. This paper integrates extant
      knowledge on family systems thinking, parenting efficacy, co-parenting, and
      family intervention with the way parents are represented and reported in
      childhood obesity research. The paper concludes with recommendations on
      terminology that can be used to describe parents and parenting figures in future
      studies.

PMID- 28430138
TI  - Nanomaterials as Assisted Matrix of Laser Desorption/Ionization Time-of-Flight
      Mass Spectrometry for the Analysis of Small Molecules.
AB  - Matrix-assisted laser desorption/ionization (MALDI), a soft ionization method,
      coupling with time-of-flight mass spectrometry (TOF MS) has become an
      indispensible tool for analyzing macromolecules, such as peptides, proteins,
      nucleic acids and polymers. However, the application of MALDI for the analysis of
      small molecules (<700 Da) has become the great challenge because of the
      interference from the conventional matrix in low mass region. To overcome this
      drawback, more attention has been paid to explore interference-free methods in
      the past decade. The technique of applying nanomaterials as matrix of laser
      desorption/ionization (LDI), also called nanomaterial-assisted laser
      desorption/ionization (nanomaterial-assisted LDI), has attracted considerable
      attention in the analysis of low-molecular weight compounds in TOF MS. This
      review mainly summarized the applications of different types of nanomaterials
      including carbon-based, metal-based and metal-organic frameworks as assisted
      matrices for LDI in the analysis of small biological molecules, environmental
      pollutants and other low-molecular weight compounds.

PMID- 28430139
TI  - The Metalloproteinase ADAM28 Promotes Metabolic Dysfunction in Mice.
AB  - Obesity and diabetes are major causes of morbidity and mortality globally. The
      current study builds upon our previous association studies highlighting that A
      Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the
      pathogenesis of obesity and type 2 diabetes in humans. Our novel study
      characterised the expression of ADAM28 in mice with the metabolic syndrome and
      used molecular inhibition approaches to investigate the functional role of ADAM28
      in the pathogenesis of high fat diet-induced obesity. We identified that ADAM28
      mRNA and protein expression was markedly increased in the livers of mice with the
      metabolic syndrome. In addition, noradrenaline, the major neurotransmitter of the
      sympathetic nervous system, results in elevated Adam28 mRNA expression in human
      monocytes. Downregulation of ADAM28 with siRNA technology resulted in a lack of
      weight gain, promotion of insulin sensitivity/glucose tolerance and decreased
      liver tumour necrosis factor-alpha (TNF-alpha) levels in our diet-induced obesity
      mouse model as well as reduced blood urea nitrogen, alkaline phosphatase and
      aspartate aminotransferase. In addition, we show that ADAM28 knock-out mice also
      displayed reduced body weight, elevated high density lipoprotein cholesterol
      levels, and reductions in blood urea nitrogen, alkaline phosphatase, and
      aspartate aminotransferase. The results of this study provide important insights
      into the pathogenic role of the metalloproteinase ADAM28 in the metabolic
      syndrome and suggests that downregulation of ADAM28 may be a potential
      therapeutic strategy in the metabolic syndrome.

PMID- 28430141
TI  - Who Is Using Outdoor Fitness Equipment and How? The Case of Xihu Park.
AB  - Outdoor fitness equipment (OFE) placed in public parks has the potential to
      encourage physical activity. However, little is known about OFE users and use
      patterns. This study employed onsite and video observations of OFE usage to
      describe user characteristics and patterns in Xihu Park. Results indicate that
      OFE in this park attracted considerable use, particularly in the early morning
      and late afternoon. During these peak-hour observations, approximately 12 users
      per hour used the OFE, with the majority being females and seniors. The triple
      arm stretch and air walker were the most popular stations. However, most OFE
      users interacted with less than three of the available six OFE stations.
      Furthermore, users spent an average of less than nine minutes on all OFE stations
      combined. While OFE equipment was well-used in this urban park, it appears users
      did not interact with OFE at rates to produce a sufficient bout or level of
      physical activity during their park visit. Further investigations of OFE are
      encouraged to determine their health impact.

PMID- 28430142
TI  - Initial Spore Density Has an Influence on Ochratoxin A Content in Aspergillus
      ochraceus CGMCC 3.4412 in PDB and Its Interaction with Seeds.
AB  - The morphology and secondary metabolism of Aspergillus spp. are associated with
      initial spore density (ISD). Fatty acids (FA) are involved in the biosynthesis of
      aflatoxins (AF) through Aspergillus quorum sensing (QS). Here, we studied how
      ochratoxin A (OTA) was regulated by spore density in Aspergillus ochraceus CGMCC
      3.4412. The results contribute to understanding the role of spore density in
      morphogenesis, OTA biosynthesis, and host-pathogen interactions. When A.
      ochraceus was grown in Potato Dextrose Broth (PDB) media at different spore
      densities (from 101 to 106 spores/mL), more OTA was produced when ISD were
      increased, but a higher level of ISD inhibited OTA biosynthesis. Seed infection
      studies showed that peanuts (Arachis hypogaea) and soybeans (Glycine max) with
      high FA content were more susceptible to OTA production when infected by A.
      ochraceus and reactive oxygen species (ROS)-induced OTA biosynthesis. These
      results suggested that FA was vital for OTA biosynthesis, and that oxidative
      stress was closely related to OTA biosynthesis in A. ochraceus.

PMID- 28430140
TI  - "Eat as If You Could Save the Planet and Win!" Sustainability Integration into
      Nutrition for Exercise and Sport.
AB  - Today's industrial food production contributes significantly to environmental
      degradation. Meat production accounts for the largest impact, including
      greenhouse gas emissions, land and water use. While food production and
      consumption are important aspects when addressing climate change, this article
      focuses predominantly on dietary change that promotes both health for planet and
      people with focus on athletes. Healthy, sustainable eating recommendations begin
      to appear in various governmental guidelines. However, there remains resistance
      to the suggested reductions in meat consumption. While food citizens are likely
      to choose what is good for them and the planet, others may not, unless healthy
      eating initiatives integrate creative food literacy approaches with experiential
      learning as a potential vehicle for change. This concept paper is organized in
      three sections: (1) Environmental impact of food; (2) health and sustainability
      connections; and (3) application in sports and exercise. For active individuals,
      this article focuses on the quantity of protein, highlighting meat and dairy, and
      quality of food, with topics such as organic production and biodiversity.
      Finally, the timing of when to integrate sustainability principles in sport
      nutrition is discussed, followed by practical applications for education and
      inclusion in team, institutional, and event operations.

PMID- 28430143
TI  - Associations between Temperature and Hospital Admissions for Subarachnoid
      Hemorrhage in Korea.
AB  - The relationship between temperature and subarachnoid hemorrhage (SAH) is less
      studied than that between temperature and myocardial infarction or other
      cardiovascular diseases. This study investigated the association between daily
      temperature and risk of SAH by analyzing the hospital admission records of
      111,316 SAH patients from 2004 to 2012 in Korea. A Poisson regression model was
      used to examine the association between temperature and daily SAH hospital
      admissions. To analyze data and identify vulnerable groups, we used the following
      subgroups: sex, age, insurance type, area (rural or urban), and different climate
      zones. We confirmed a markedly higher SAH risk only for people of low
      socioeconomic status in both hot and cold temperatures; the relative risk (RR) in
      the Medicaid group was significantly increased and ranged from 1.04 to 1.11 for
      cold temperatures and 1.10 to 1.11 for hot temperatures. For the National Health
      Insurance group, the RR was increased to 1.02 for the maximum temperature only.
      The increased risk for SAH was highest in the temperate zone. An increase above
      the heat threshold temperature and a decrease below the cold threshold
      temperature were correlated with an increased risk of SAH in susceptible
      populations and were associated with different lag effects and RRs.

PMID- 28430144
TI  - A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways
      in Porcine Skeletal Muscle Affected by Dietary Lysine.
AB  - Nine crossbred finishing barrows (body weight 94.4 +/- 6.7 kg) randomly assigned
      to three dietary treatments were used to investigate the effects of dietary
      lysine on muscle growth related metabolic and signaling pathways. Muscle samples
      were collected from the longissimus dorsi of individual pigs after feeding the
      lysine-deficient (4.30 g/kg), lysine-adequate (7.10 g/kg), or lysine-excess (9.80
      g/kg) diet for five weeks, and the total RNA was extracted afterwards. Affymetrix
      Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211
      genes. Statistical ANOVA analysis of the microarray data showed that 674
      transcripts were differentially expressed (at p <= 0.05 level); 60 out of 131
      transcripts (at p <= 0.01 level) were annotated in the NetAffx database.
      Ingenuity pathway analysis showed that dietary lysine deficiency may lead to: (1)
      increased muscle protein degradation via the ubiquitination pathway as indicated
      by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA; (2) reduced muscle protein
      synthesis via the up-regulated RND3 and ZIC1 mRNA; (3) increased serine and
      glycine synthesis via the up-regulated PHGDH and PSPH mRNA; and (4) increased
      lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine
      excess may lead to: (1) decreased muscle protein degradation via the down
      regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA; and (2) reduced lipid
      biosynthesis via the down-regulated CFD and ME1 mRNA. Collectively, dietary
      lysine may function as a signaling molecule to regulate protein turnover and
      lipid metabolism in the skeletal muscle of finishing pigs.

PMID- 28430145
TI  - The Association of Ankle Brachial Index, Protein-Energy Wasting, and Inflammation
      Status with Cardiovascular Mortality in Patients on Chronic Hemodialysis.
AB  - Protein-energy wasting (PEW) is highly prevalent in hemodialysis (HD) patients.
      We investigated the association of abnormal ankle brachial index (ABI), PEW, and
      chronic inflammation status with clinical prognosis in HD patients. A total of
      973 HD patients were enrolled and were followed-up for 8 years. As a marker of
      the PEW, geriatric nutritional risk index (GNRI) was used. Cut-off levels were
      91.2 for GNRI defined from previous studies and 1.9 mg/L for C-reactive protein
      (CRP) as median value, respectively. Abnormal ABI was seen in 332 (34.1%)
      patients. Declined GNRI and elevated CRP levels were independently associated
      with abnormal ABI (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99,
      p = 0.0009 and OR 1.40, 95% CI 1.07-1.83, p = 0.013, respectively). GNRI levels
      were also independently correlated with CRP levels (beta = -0.126, p < 0.0001).
      During follow-up period, 283 (29.1%) patients died, including 123 (12.6%) due to
      cardiovascular disease (CVD). Abnormal ABI (adjusted hazard ratio (HR) 1.62, 95%
      CI 1.13-2.32, p = 0.0096), GNRI < 91.2 (adjusted HR 1.57, 95% CI 1.06-2.33, p =
      0.023) and CRP > 1.9 mg/L (adjusted HR 1.89, 95% CI 1.31-2.77, p = 0.0007)
      independently predicted mortality due to CVD, respectively. In conclusion,
      abnormal ABI, GNRI, and CRP levels were closely associated with each other, and
      the combination of these variables increase their predictive values for the risk
      of mortality due to CVD and all-cause mortality in HD patients.

PMID- 28430146
TI  - A New Method for Single-Epoch Ambiguity Resolution with Indoor Pseudolite
      Positioning.
AB  - Ambiguity resolution (AR) is crucial for high-precision indoor pseudolite
      positioning. Due to the existing characteristics of the pseudolite positioning
      system, such as the geometry structure of the stationary pseudolite which is
      consistently invariant, the indoor signal is easy to interrupt and the first
      order linear truncation error cannot be ignored, and a new AR method based on the
      idea of the ambiguity function method (AFM) is proposed in this paper. The
      proposed method is a single-epoch and nonlinear method that is especially well
      suited for indoor pseudolite positioning. Considering the very low computational
      efficiency of conventional AFM, we adopt an improved particle swarm optimization
      (IPSO) algorithm to search for the best solution in the coordinate domain, and
      variances of a least squares adjustment is conducted to ensure the reliability of
      the solving ambiguity. Several experiments, including static and kinematic tests,
      are conducted to verify the validity of the proposed AR method. Numerical results
      show that the IPSO significantly improved the computational efficiency of AFM and
      has a more elaborate search ability compared to the conventional grid searching
      method. For the indoor pseudolite system, which had an initial approximate
      coordinate precision better than 0.2 m, the AFM exhibited good performances in
      both static and kinematic tests. With the corrected ambiguity gained from our
      proposed method, indoor pseudolite positioning can achieve centimeter-level
      precision using a low-cost single-frequency software receiver.

PMID- 28430147
TI  - Suitability of Strain Gage Sensors for Integration into Smart Sport Equipment: A
      Golf Club Example.
AB  - Wearable devices and smart sport equipment are being increasingly used in amateur
      and professional sports. Smart sport equipment employs various sensors for
      detecting its state and actions. The correct choice of the most appropriate
      sensor(s) is of paramount importance for efficient and successful operation of
      sport equipment. When integrated into the sport equipment, ideal sensors are
      unobstructive, and do not change the functionality of the equipment. The article
      focuses on experiments for identification and selection of sensors that are
      suitable for the integration into a golf club with the final goal of their use in
      real time biofeedback applications. We tested two orthogonally affixed strain
      gage (SG) sensors, a 3-axis accelerometer, and a 3-axis gyroscope. The strain
      gage sensors are calibrated and validated in the laboratory environment by a
      highly accurate Qualisys Track Manager (QTM) optical tracking system. Field test
      results show that different types of golf swing and improper movement in early
      phases of golf swing can be detected with strain gage sensors attached to the
      shaft of the golf club. Thus they are suitable for biofeedback applications to
      help golfers to learn repetitive golf swings. It is suggested that the use of
      strain gage sensors can improve the golf swing technical error detection accuracy
      and that strain gage sensors alone are enough for basic golf swing analysis. Our
      final goal is to be able to acquire and analyze as many parameters of a smart
      golf club in real time during the entire duration of the swing. This would give
      us the ability to design mobile and cloud biofeedback applications with terminal
      or concurrent feedback that will enable us to speed-up motor skill learning in
      golf.

PMID- 28430148
TI  - A Rapid Magnetic Solid Phase Extraction Method Followed by Liquid Chromatography
      Tandem Mass Spectrometry Analysis for the Determination of Mycotoxins in Cereals.
AB  - Mycotoxins can contaminate various food commodities, including cereals. Moreover,
      mycotoxins of different classes can co-contaminate food, increasing human health
      risk. Several analytical methods have been published in the literature dealing
      with mycotoxins determination in cereals. Nevertheless, in the present work, the
      aim was to propose an easy and effective system for the extraction of six of the
      main mycotoxins from corn meal and durum wheat flour, i.e., the main four
      aflatoxins, ochratoxin A, and the mycoestrogen zearalenone. The developed method
      exploited magnetic solid phase extraction (SPE), a technique that is attracting
      an increasing interest as an alternative to classical SPE. Therefore, the use of
      magnetic graphitized carbon black as a suitable extracting material was tested.
      The same magnetic material proved to be effective in the extraction of
      mycoestrogens from milk, but has never been applied to complex matrices as
      cereals. Ultra high-performance liquid chromatography tandem mass spectrometry
      was used for detection. Recoveries were >60% in both cereals, even if the matrix
      effects were not negligible. The limits of quantification of the method results
      were comparable to those obtained by other two magnetic SPE-based methods applied
      to cereals, which were limited to one or two mycotoxins, whereas in this work the
      investigated mycotoxins belonged to three different chemical classes.

PMID- 28430149
TI  - Synthesis and Antiviral Activity of Novel 1,4-Pentadien-3-one Derivatives
      Containing a 1,3,4-Thiadiazole Moiety.
AB  - 1,4-Pentadien-3-one derivatives derived from curcumin possess excellent
      inhibitory activity against plant viruses. On the basis of this finding, a series
      of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety
      were designed and synthesized, and their structures confirmed by IR, 1H-NMR, and
      13C-NMR spectroscopy and elemental analysis. The antiviral activities of the
      title compounds were evaluated against tobacco mosaic virus (TMV) and cucumber
      mosaic virus (CMV) in vivo. The assay results showed that most of compounds had
      remarkable antiviral activities against TMV and CMV, among which compounds 4b,
      4h, 4i, 4k, 4o, and 4q exhibited good curative, protection, and inactivation
      activity against TMV. Compounds 4h, 4i, 4k, 4l, 4o, and 4q exhibited excellent
      protection activity against TMV, with EC50 values of 105.01, 254.77, 135.38,
      297.40, 248.18, and 129.87 MUg/mL, respectively, which were superior to that of
      ribavirin (457.25 ug/mL). In addition, preliminary SARs indicated that small
      electron-withdrawing groups on the aromatic ring were favorable for anti-TMV
      activity. This finding suggests that 1,4-pentadien-3-one derivatives containing a
      1,3,4-thiadiazole moiety may be considered as potential lead structures for
      discovering new antiviral agents.

PMID- 28430150
TI  - Synthesis and Self-Assembly of Shape Amphiphiles Based on POSS-Dendron
      Conjugates.
AB  - Shape has been increasingly recognized as an important factor for self-assembly.
      In this paper, a series of shape amphiphiles have been built by linking
      polyhedral oligomeric silsesquioxane (POSS) and a dendron via linkers of
      different lengths. Three conjugates of octahedral silsesquioxanes (T8-POSS) and
      dendron are designed and synthesized and are referred to as isobutyl T8-POSS
      gallic acid derivatives (BPOSS-GAD-1, BPOSS-GAD-2, BPOSS-GAD-3). These samples
      have been fully characterized by 1H-NMR, 13C-NMR, Fourier transform infrared (FT
      IR) spectroscopy and matrix-assisted laser desorption/ionization time of flight
      (MALDI-TOF) mass spectrometry to establish their chemical identity and purity.
      Driven by different interactions between POSS and dendron, ordered superstructure
      can be found upon self-assembly. The stabilities and structures of these samples
      are further studied by using differential scanning calorimetry (DSC), small-angle
      X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXD), and molecular
      simulations. The results show that their melting points range from 74  degrees C
      to 143  degrees C and the molecular packing schemes in the assemblies can form
      lamellar structure of BPOSS-GAD-3 as determined by the different linkers.

PMID- 28430152
TI  - Improved Synthesis of 1-O-Acyl-beta-d-Glucopyranose Tetraacetates.
AB  - An improved synthesis of 1-O-acyl glucosyl esters that avoids the use of
      expensive Ag reagents as well as the hydrolysis of unstable glucosyl bromides is
      reported. Notably, beta-configuration products were obtained exclusively in good
      yields.

PMID- 28430153
TI  - A Novel Method of Localization for Moving Objects with an Alternating Magnetic
      Field.
AB  - Magnetic detection technology has wide applications in the fields of geological
      exploration, biomedical treatment, wreck removal and localization of unexploded
      ordinance. A large number of methods have been developed to locate targets with
      static magnetic fields, however, the relation between the problem of localization
      of moving objectives with alternating magnetic fields and the localization with a
      static magnetic field is rarely studied. A novel method of target localization
      based on coherent demodulation was proposed in this paper. The problem of
      localization of moving objects with an alternating magnetic field was transformed
      into the localization with a static magnetic field. The Levenberg-Marquardt (L-M)
      algorithm was applied to calculate the position of the target with magnetic field
      data measured by a single three-component magnetic sensor. Theoretical simulation
      and experimental results demonstrate the effectiveness of the proposed method.

PMID- 28430151
TI  - Na/K Pump and Beyond: Na/K-ATPase as a Modulator of Apoptosis and Autophagy.
AB  - Lung cancer is a leading cause of global cancer deaths. Na/K-ATPase has been
      studied as a target for cancer treatment. Cardiotonic steroids (CS) trigger
      intracellular signalling upon binding to Na/K-ATPase. Normal lung and tumour
      cells frequently express different pump isoforms. Thus, Na/K-ATPase is a powerful
      target for lung cancer treatment. Drugs targeting Na/K-ATPase may induce
      apoptosis and autophagy in transformed cells. We argue that Na/K-ATPase has a
      role as a potential target in chemotherapy in lung cancer treatment. We discuss
      the effects of Na/K-ATPase ligands and molecular pathways inducing deleterious
      effects on lung cancer cells, especially those leading to apoptosis and
      autophagy.

PMID- 28430155
TI  - Dynamic Construction Scheme for Virtualization Security Service in Software
      Defined Networks.
AB  - For a Software Defined Network (SDN), security is an important factor affecting
      its large-scale deployment. The existing security solutions for SDN mainly focus
      on the controller itself, which has to handle all the security protection tasks
      by using the programmability of the network. This will undoubtedly involve a
      heavy burden for the controller. More devastatingly, once the controller itself
      is attacked, the entire network will be paralyzed. Motivated by this, this paper
      proposes a novel security protection architecture for SDN. We design a security
      service orchestration center in the control plane of SDN, and this center
      physically decouples from the SDN controller and constructs SDN security
      services. We adopt virtualization technology to construct a security meta
      function library, and propose a dynamic security service composition construction
      algorithm based on web service composition technology. The rule-combining method
      is used to combine security meta-functions to construct security services which
      meet the requirements of users. Moreover, the RETE algorithm is introduced to
      improve the efficiency of the rule-combining method. We evaluate our solutions in
      a realistic scenario based on OpenStack. Substantial experimental results
      demonstrate the effectiveness of our solutions that contribute to achieve the
      effective security protection with a small burden of the SDN controller.

PMID- 28430156
TI  - Zero-Sum Matrix Game with Payoffs of Dempster-Shafer Belief Structures and Its
      Applications on Sensors.
AB  - The zero-sum matrix game is one of the most classic game models, and it is widely
      used in many scientific and engineering fields. In the real world, due to the
      complexity of the decision-making environment, sometimes the payoffs received by
      players may be inexact or uncertain, which requires that the model of matrix
      games has the ability to represent and deal with imprecise payoffs. To meet such
      a requirement, this paper develops a zero-sum matrix game model with Dempster
      Shafer belief structure payoffs, which effectively represents the ambiguity
      involved in payoffs of a game. Then, a decomposition method is proposed to
      calculate the value of such a game, which is also expressed with belief
      structures. Moreover, for the possible computation-intensive issue in the
      proposed decomposition method, as an alternative solution, a Monte Carlo
      simulation approach is presented, as well. Finally, the proposed zero-sum matrix
      games with payoffs of Dempster-Shafer belief structures is illustratively applied
      to the sensor selection and intrusion detection of sensor networks, which shows
      its effectiveness and application process.

PMID- 28430154
TI  - Circadian Rhythm Neuropeptides in Drosophila: Signals for Normal Circadian
      Function and Circadian Neurodegenerative Disease.
AB  - Circadian rhythm is a ubiquitous phenomenon in many organisms ranging from
      prokaryotes to eukaryotes. During more than four decades, the intrinsic and
      exogenous regulations of circadian rhythm have been studied. This review
      summarizes the core endogenous oscillation in Drosophila and then focuses on the
      neuropeptides, neurotransmitters and hormones that mediate its outputs and
      integration in Drosophila and the links between several of these (pigment
      dispersing factor (PDF) and insulin-like peptides) and neurodegenerative disease.
      These signaling molecules convey important network connectivity and signaling
      information for normal circadian function, but PDF and insulin-like peptides can
      also convey signals that lead to apoptosis, enhanced neurodegeneration and
      cognitive decline in flies carrying circadian mutations or in a senescent state.

PMID- 28430157
TI  - Development of User-Friendly Method to Distinguish Subspecies of the Korean
      Medicinal Herb Perilla frutescens Using Multiplex-PCR.
AB  - Perilla (Perilla frutescens) is an economically and culturally important plant in
      East Asia. Plant breeding between cultivars has enhanced the genetic diversity of
      perilla overall, but means that functionally diverse subspecies are more
      difficult to identify and distinguish. In this study, we developed gene-based DNA
      markers to distinguish between the Korean herbal medicinal perilla varieties. We
      identified informative simple sequence repeat (SSR) regions on the promoter
      regions of the Myb-P1 and dihydroflavonol 4-reductase (DFR) genes, as well as a
      large insertion-deletion (indel) region in the limonene synthase (LS) gene, and
      developed markers to characterize the distinct subspecies differences (PfMyb
      P1pro, PfDFRpro, and PfLS, respectively). Using the PfLS primers, a 430-bp region
      could be amplified from P. frutescens var. acuta, crispa, and f. viridis (known
      as Jasoyeop, Jureum-soyeop, and Chungsoyeop, respectively), but not from P.
      frutescens var. japonica (Dlggae). The PfMybpro primers resulted in PCR products
      of 314 or 316, 330, 322, and 315 bp from Dlggae, Jasoyeop, Jureum-soyeop, and
      Chungsoyeop, respectively, and the PfDFRpro primers resulted in products of 189
      or 202, 187 or 189, 185 or 189, and 193bp, respectively, for the four perilla
      subspecies. Combining these three reactions into a single multiplex PCR approach
      resulted in subspecies-specific PCR band patterns for six common types of
      commercial perilla, distinguishing between three varieties of Dlggae (Cham
      Dlggae, Ip-Dlggae, and Bora-Dlggae), as well as identifying Jasoyeop, Jureum
      soyeop, and Chungsoyeop. These user-friendly markers will be valuable as a simple
      and efficient method for identifying the Korean medicinal herb Jasoyeop, as well
      as distinguishing between other functionally distinct subspecies, which may have
      broad applications in the Korean herbal industry.

PMID- 28430158
TI  - Identification of Tight-Binding Plasmepsin II and Falcipain 2 Inhibitors in
      Aqueous Extracts of Marine Invertebrates by the Combination of Enzymatic and
      Interaction-Based Assays.
AB  - Natural products from marine origin constitute a very promising and underexplored
      source of interesting compounds for modern biotechnological and pharmaceutical
      industries. However, their evaluation is quite challenging and requires
      specifically designed assays to reliably identify the compounds of interest in a
      highly heterogeneous and interfering context. In the present study, we describe a
      general strategy for the confident identification of tight-binding protease
      inhibitors in the aqueous extracts of 62 Cuban marine invertebrates, using
      Plasmodium falciparum hemoglobinases Plasmepsin II and Falcipain 2 as model
      enzymes. To this end, we first developed a screening strategy that combined
      enzymatic with interaction-based assays and then validated screening conditions
      using five reference extracts. Interferences were evaluated and minimized. The
      results from the massive screening of such extracts, the validation of several
      hits by a variety of interaction-based assays and the purification and functional
      characterization of PhPI, a multifunctional and reversible tight-binding
      inhibitor for Plasmepsin II and Falcipain 2 from the gorgonian Plexaura
      homomalla, are presented.

PMID- 28430159
TI  - Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic
      Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial.
AB  - BACKGROUND: Low-molecular-weight fucoidan (LMF) is widely used as a food
      supplement for cancer patients. However, all of the studies are in vitro or were
      conducted using mice. Therefore, powerful clinical evidence for LMF use is
      relatively weak. This study aimed to evaluate the efficacy of LMF as a
      supplemental therapy to chemo-target agents in metastatic colorectal cancer
      (mCRC) patients. METHODS: We conducted a prospective, randomized, double-blind,
      controlled trial to evaluate the efficacy of LMF as a supplemental therapy to
      chemotarget agents in patients with metastatic colorectal cancer (mCRC). Sixty
      eligible patients with mCRC were included. Finally, 54 patients were enrolled, of
      whom 28 were included in the study group and 26 in the control group. The primary
      endpoint was the disease control rate (DCR), and secondary endpoints included the
      overall response rate (ORR), progression-free survival (PFS), overall survival
      (OS), adverse effects (AEs), and quality of life (QOL). RESULTS: The DCRs were
      92.8% and 69.2% in the study and control groups, respectively (p = 0.026), in a
      median follow-up period of 11.5 months. The OS, PFS, ORR, AEs, and QOL did not
      significantly differ between the two groups. CONCLUSION: This is the first
      clinical trial evaluating the efficacy of LMF as a supplemental therapy in the
      management of patients with mCRC. The results indicate that LMF combined with
      chemotarget agents significantly improved the DCR.

PMID- 28430161
TI  - A National Study of Social Media, Television, Radio, and Internet Usage of Adults
      by Sexual Orientation and Smoking Status: Implications for Campaign Design.
AB  - Background: Smoking rates among lesbian, gay, and bisexual (LGB) people
      significantly exceed that of heterosexuals. Media interventions are an important
      part of tobacco control efforts, but limited information is available on LGB
      people's media use. Methods: A nationally representative sample of 12,900 U.S.
      adults completed an online questionnaire assessing media use, smoking status, and
      demographic information. Multivariable logistic regression was used to assess
      relationships between media use with sexual orientation and smoking status.
      Results: A total of 590 (4.6%) respondents identified as LGB, of which 29% were
      smokers. Regardless of sexual orientation and smoking status, the Internet was
      the most popular media channel used, followed by television and radio. LGB
      respondents had significantly greater odds of having accounts on social media
      websites, accessing Facebook daily, and being a frequent Internet user, compared
      to heterosexual respondents. Similar media use was found between smokers and non
      smokers, but smokers had greater odds of being frequent television viewers and
      frequent Internet users, compared to non-smokers. Conclusions: Compared to
      heterosexuals, LGB respondents reported greater use of the Internet, especially
      social media. Media campaigns targeting LGB populations can maximize reach by
      utilizing social media alongside traditional media channels.

PMID- 28430160
TI  - Subverting Host Cell P21-Activated Kinase: A Case of Convergent Evolution across
      Pathogens.
AB  - Intracellular pathogens have evolved a wide range of strategies to not only
      escape from the immune systems of their hosts, but also to directly exploit a
      variety of host factors to facilitate the infection process. One such strategy is
      to subvert host cell signalling pathways to the advantage of the pathogen. Recent
      research has highlighted that the human serine/threonine kinase PAK, or p21
      activated kinase, is a central component of host-pathogen interactions in many
      infection systems involving viruses, bacteria, and eukaryotic pathogens. PAK
      paralogues are found in most mammalian tissues, where they play vital roles in a
      wide range of functions. The role of PAKs in cell proliferation and survival, and
      their involvement in a number of cancers, is of great interest in the context of
      drug discovery. In this review we discuss the latest insights into the
      surprisingly central role human PAK1 plays for the infection by such different
      infectious disease agents as viruses, bacteria, and parasitic protists. It is our
      intention to open serious discussion on the applicability of PAK inhibitors for
      the treatment, not only of neoplastic diseases, which is currently the primary
      objective of drug discovery research targeting these enzymes, but also of a wide
      range of infectious diseases.

PMID- 28430162
TI  - Ameliorative Effects and Possible Molecular Mechanism of Action of Black Ginseng
      (Panax ginseng) on Acetaminophen-Mediated Liver Injury.
AB  - Background: Frequent overdosing of acetaminophen (APAP) has become the major
      cause of acute liver injury (ALI). The present study aimed to evaluate the
      potential hepatoprotective effects of black ginseng (BG) on APAP-induced mice
      liver injuries and the underlying mechanisms of action were further investigated
      for the first time. Methods: Mice were treated with BG (300, 600 mg/kg) by oral
      gavage once a day for seven days. On the 7th day, all mice were treated with 250
      mg/kg APAP which caused severe liver injury after 24 h and hepatotoxicity was
      assessed. Results: Our results showed that pretreatment with BG significantly
      decreased the levels of serum alanine aminotransferase (ALT) and aspartate
      transaminase (AST) compared with the APAP group. Meanwhile, hepatic antioxidant
      including glutathione (GSH) was elevated compared with the APAP group. In
      contrast, a significant decrease of the levels of the lipid peroxidation product
      malondialdehyde (MDA) was observed in the BG-treated groups compared with the
      APAP group. These effects were associated with significant increases of
      cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) levels in liver tissues.
      Moreover, BG supplementation suppressed activation of apoptotic pathways through
      increasing Bcl-2 and decreasing Bax protein expression levels according to
      western blotting analysis. Histopathological examination revealed that BG
      pretreatment significantly inhibited APAP-induced necrosis and inflammatory
      infiltration in liver tissues. Biological indicators of nitrative stress like 3
      nitrotyrosine (3-NT) were also inhibited after pretreatment with BG, compared
      with the APAP group. Conclusions: The results clearly suggest that the underlying
      molecular mechanisms of action of BG-mediated alleviation of APAP-induced
      hepatotoxicity may involve its anti-oxidant, anti-apoptotic, anti-inflammatory
      and anti-nitrative effects.

PMID- 28430164
TI  - State Estimation Using Dependent Evidence Fusion: Application to Acoustic
      Resonance-Based Liquid Level Measurement.
AB  - Estimating the state of a dynamic system via noisy sensor measurement is a common
      problem in sensor methods and applications. Most state estimation methods assume
      that measurement noise and state perturbations can be modeled as random variables
      with known statistical properties. However in some practical applications,
      engineers can only get the range of noises, instead of the precise statistical
      distributions. Hence, in the framework of Dempster-Shafer (DS) evidence theory, a
      novel state estimatation method by fusing dependent evidence generated from state
      equation, observation equation and the actual observations of the system states
      considering bounded noises is presented. It can be iteratively implemented to
      provide state estimation values calculated from fusion results at every time
      step. Finally, the proposed method is applied to a low-frequency acoustic
      resonance level gauge to obtain high-accuracy measurement results.

PMID- 28430165
TI  - Treatments for Latrodectism-A Systematic Review on Their Clinical Effectiveness.
AB  - Latrodectism or envenomation by widow-spiders is common and clinically
      significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the
      venom that results in toxic effects observed in humans. Symptoms may be
      incapacitating and include severe pain that can persist for days. The management
      of mild to moderate latrodectism is primarily supportive while severe cases have
      variously been treated with intravenous calcium, muscle relaxants, widow-spider
      antivenom and analgesic opioids. The object of this systematic review is to
      examine the literature on the clinical effectiveness of past and current
      treatments for latrodectism. MEDLINE, EMBASE and Google Scholar were searched
      from 1946 to December 2016 to identify clinical studies on the treatment of
      latrodectism. Studies older than 40 years and not in English were not reviewed.
      There were only two full-publications and one abstract of placebo-controlled
      randomised trials on antivenom use for latrodectism. Another two randomised
      comparative trials compared the route of administration of antivenom for
      latrodectism. There were fourteen case series (including two abstracts), fourteen
      case reports and one letter investigating drug treatments for latrodectism with
      the majority of these also including antivenom for severe latrodectism. Antivenom
      with opioid analgesia is often the major treatment reported for latrodectism
      however; recent high quality evidence has cast doubt on the clinical
      effectiveness of this combination and suggests that other treatments need to be
      investigated.

PMID- 28430166
TI  - "French Phage Network"-Second Meeting Report.
AB  - The study of bacteriophages (viruses of bacteria) includes a variety of
      approaches, such as structural biology, genetics, ecology, and evolution, with
      increasingly important implications for therapeutic and industrial uses.
      Researchers working with phages in France have recently established a network to
      facilitate the exchange on complementary approaches, but also to engage new
      collaborations. Here, we provide a summary of the topics presented during the
      second meeting of the French Phage Network that took place in Marseille in
      November 2016.

PMID- 28430169
TI  - Low--quality manufactured immunoenzymatic assay kits as a source of confusion in
      science.

PMID- 28430167
TI  - Induced Pluripotent Stem Cell Modeling of Gaucher's Disease: What Have We
      Learned?
AB  - Gaucher's disease (GD) is the most frequently inherited lysosomal storage
      disease, presenting both visceral and neurologic symptoms. Mutations in acid beta
      glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting
      glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options
      are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT).
      However, neither of these approaches is effective in treating the neurological
      aspect of the disease. The use of small pharmacological compounds that act as
      molecular chaperones is a promising approach that is still experimental. In
      recent years, an association between GD and Parkinson like synucleinopathies has
      been discovered. Since 1992, a number of mouse models of GD have been the
      developed and partially reproduce phenotype of the disease. More recently, the
      discovery of direct reprograming has allowed the derivation of induced
      pluripotent stem cells (iPSc) from fibroblasts obtained from GD patients. iPSc
      can be expanded indefinitely in vitro and differentiated to macrophages and
      neurons, the main relevant cell types involved in GD. In this work, we review
      iPSc models of GD and summarize what we have learned from this system.

PMID- 28430170
TI  - Current management of gout: practical messages from 2016 EULAR guidelines.
AB  - The European League Against Rheumatism published updated recommendations for the
      management of gout in 2016, comprising 3 overarching principles and 11 key
      recommendations for clinical practice. Patient education about the
      pathophysiology of gout and its comorbidities, as well as the existence of
      effective treatments are important, and understanding the principles of managing
      acute attacks and eliminating urate crystals by lifelong lowering of the serum
      urate (SU) below a target level are essential. Advice about lifestyle, diet,
      weight, and other risk factors, as well as the need to screen for, and manage,
      comorbidities is emphasized. For the treatment of flares, colchicine,
      nonsteroidal anti-inflammatory drugs (NSAIDs), and oral or intraarticular
      steroids, or a combination thereof, are recommended. In patients with frequent
      flares and contraindications to colchicine, NSAIDs, and corticosteroids, an
      interleukin-1 blocker should be considered. Urate-lowering therapy (ULT) should
      be discussed from the first presentation of the disease, and SU levels should be
      maintained at less than 6 mg/dl (360 umol/l), or less than 5 mg/dl (300 umol/l)
      in patients with severe gout. Allopurinol is recommended as first-line ULT with
      dose adjustment according to renal function. If the SU target cannot be achieved
      with allopurinol, then febuxostat, a uricosuric, or combining a xanthine oxidase
      inhibitor with a uricosuric should be considered. All ULTs should be started at
      low dose and titrated upwards until the SU target is achieved. Unless
      contraindicated, flare prophylaxis with low-dose colchicine or with NSAIDs at low
      dosage is recommended during the first 6 months of ULT. In patients with
      refractory gout, pegloticase can be considered.

PMID- 28430163
TI  - Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour
      Drug Resistance and Cancer Stem Cells.
AB  - Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a
      mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to
      initiate invasion and metastasis. In addition, it is becoming clear that is
      instrumental to both the development of drug resistance by tumour cells and in
      the generation and maintenance of cancer stem cells. EMT is thus a pivotal
      process during tumour progression and poses a major barrier to the successful
      treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to
      regulate both gene expression and chromatin structure. One type of ncRNA, called
      long non-coding RNAs (lncRNAs), has become increasingly recognized as being both
      highly dysregulated in cancer and to play a variety of different roles in
      tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as
      key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have
      been associated with the EMT process in cancer and the variety of molecular
      mechanisms and signalling pathways through which they regulate EMT, and finally
      discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug
      resistance and the cancer stem cell phenotype.

PMID- 28430171
TI  - The prognostic value of 18-FDG positron emission tomography in T cell non-Hodgkin
      lymphoma.

PMID- 28430172
TI  - EZH2 alterations in follicular lymphoma: biological and clinical correlations.
AB  - The histone methyltransferase EZH2 has an essential role in the development of
      follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been
      described in 25% of FL patients and induce aberrant methylation of histone H3
      lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology.
      Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy
      number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL
      patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n=55)
      and H3K27 methylation (n=63) profiles were also evaluated. In total, 37% of
      patients (59/159) harbored an alteration in the EZH2 gene (mutation n=46, gain
      n=23). Both types of alterations were associated with highly similar
      transcriptional changes, with increased proliferation programs. An H3K27me3/me2
      IHC score fully distinguished mutated from wild-type samples, showing its
      applicability as surrogate for EZH2 mutation analysis. However, this score did
      not predict the presence of gains at the EZH2 locus. The presence of an EZH2
      genetic alteration was an independent factor associated with a longer progression
      free survival (hazard ratio 0.58, 95% confidence interval 0.36-0.93, P=0.025). We
      propose that the copy-number status of EZH2 should also be considered when
      evaluating patient stratification and selecting patients for EZH2 inhibitor
      targeted therapies.

PMID- 28430173
TI  - Liver function test abnormalities and their clinical relevance in primary
      myelofibrosis.

PMID- 28430168
TI  - Classical Swine Fever-An Updated Review.
AB  - Classical swine fever (CSF) remains one of the most important transboundary viral
      diseases of swine worldwide. The causative agent is CSF virus, a small, enveloped
      RNA virus of the genus Pestivirus. Based on partial sequences, three genotypes
      can be distinguished that do not, however, directly correlate with virulence.
      Depending on both virus and host factors, a wide range of clinical syndromes can
      be observed and thus, laboratory confirmation is mandatory. To this means, both
      direct and indirect methods are utilized with an increasing degree of
      commercialization. Both infections in domestic pigs and wild boar are of great
      relevance; and wild boars are a reservoir host transmitting the virus
      sporadically also to pig farms. Control strategies for epidemic outbreaks in free
      countries are mainly based on classical intervention measures; i.e., quarantine
      and strict culling of affected herds. In these countries, vaccination is only an
      emergency option. However, live vaccines are used for controlling the disease in
      endemically infected regions in Asia, Eastern Europe, the Americas, and some
      African countries. Here, we will provide a concise, updated review on virus
      properties, clinical signs and pathology, epidemiology, pathogenesis and immune
      responses, diagnosis and vaccination possibilities.

PMID- 28430174
TI  - Whole-exome analysis reveals novel somatic genomic alterations associated with
      cell of origin in diffuse large B-cell lymphoma.

PMID- 28430175
TI  - Carfilzomib-lenalidomide-dexamethasone vs lenalidomide-dexamethasone in relapsed
      multiple myeloma by previous treatment.
AB  - Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in
      combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or
      refractory multiple myeloma. The approval of carfilzomib-lenalidomide
      dexamethasone (KRd) was based on results from the randomized, phase 3 study
      ASPIRE (NCT01080391), which showed KRd significantly improved progression-free
      survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690;
      P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of
      previous lines of therapy and previous exposure to bortezomib, thalidomide or
      lenalidomide. Treatment with KRd led to a 12-month improvement in median PFS vs
      Rd after first relapse (HR 0.713) and a 9-month improvement after ?2 previous
      lines of therapy (HR 0.720). Treatment with KRd led to an approximate 8-month
      improvement vs Rd in median PFS in bortezomib-exposed patients (HR 0.699), a 15
      month improvement in thalidomide-exposed patients (HR 0.587) and a 5-month
      improvement in lenalidomide-exposed patients (HR 0.796). Objective response and
      complete response or better rates were higher with KRd vs Rd, irrespective of
      previous treatment. KRd had a favorable benefit-risk profile and should be
      considered an appropriate treatment option for patients with 1 or ?2 previous
      lines of therapy and those previously exposed to bortezomib, thalidomide or
      lenalidomide.

PMID- 28430176
TI  - Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP
      treated patients with diffuse large B-cell lymphoma.
AB  - The absolute peripheral blood lymphocyte count at diagnosis is known to be a
      strong prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL)
      treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
      (R-CHOP), but it remains unclear as to which peripheral blood lymphocyte
      population is reflective of DLBCL prognosis. In this cohort, 355 patients with
      DLBCL treated with R-CHOP from 2006 to 2013 were analyzed. The low absolute CD4+
      T-cell count (ACD4C) at diagnosis negatively correlated with the overall response
      rate and the complete response rate significantly (P<0.00001). An ACD4C<343 *
      106/l had a significant negative impact on the 5-year progression-free survival
      and the overall survival as compared with an ACD4C?343 * 106/l (73.7% (95%
      confidence interval (CI)=66.7-79.5) versus 50.3% (95% CI=39.0-60.6), P<0.00001
      and 83.3% (95% CI=77.1-88.0) versus 59.0% (95% CI=47.9-68.5), P<0.00000001,
      respectively). Multivariate analysis revealed that the ACD4C was an independent
      prognostic marker (hazard ratio=2.2 (95% CI=1.3-3.7), P<0.01). In conclusion, a
      low ACD4C at diagnosis served as an independent poor prognostic marker in
      patients with DLBCL.

PMID- 28430177
TI  - The prevalence of visual impairment and blindness in underserved rural areas: a
      crucial issue for future.
AB  - PurposeTo determine the prevalence of visual impairment and blindness in
      underserved Iranian villages and to identify the most common cause of visual
      impairment and blindness.Patients and methodsMultistage cluster sampling was used
      to select the participants who were then invited to undergo complete
      examinations. Optometric examinations including visual acuity, and refraction
      were performed for all individuals. Ophthalmic examinations included slit-lamp
      biomicroscopy and ophthalmoscopy. Visual impairment was determined according to
      the definitions of the WHO and presenting vision.ResultsOf 3851 selected
      individuals, 3314 (86.5%) participated in the study. After using the exclusion
      criteria, the present report was prepared based on the data of 3095 participants.
      The mean age of the participants was 37.6+/-20.7 years (3-93 years). The
      prevalence of visual impairment and blindness was 6.43% (95% confidence interval
      (CI): 3.71-9.14) and 1.18% (95% CI: 0.56-1.79), respectively. The prevalence of
      visual impairment varied from 0.75% in participants aged less than 5 years to
      38.36% in individuals above the age of 70 years. Uncorrected refractive errors
      and cataract were the first and second leading causes of visual impairment;
      moreover, cataract and refractive errors were responsible for 35.90 and 20.51% of
      the cases of blindness, respectively.ConclusionThe prevalence of visual
      impairment was markedly high in this study. Lack of access to health services was
      the main reason for the high prevalence of visual impairment in this study.
      Cataract and refractive errors are responsible for 80% of visual impairments
      which can be due to poverty in underserved villages.

PMID- 28430178
TI  - Endothelial keratoplasty: is Descemet membrane endothelial keratoplasty the Holy
      Grail of lamellar surgery? No.

PMID- 28430179
TI  - Response to 'Comment on The evidence informing the surgeon's selection of
      intraocular lens on the basis of light transmittance properties'.

PMID- 28430180
TI  - Comment on 'The evidence informing the surgeon's selection of intraocular lens on
      the basis of light transmittance properties'.

PMID- 28430181
TI  - Supervised learning and dimension reduction techniques for quantification of
      retinal fluid in optical coherence tomography images.
AB  - PurposeThe purpose of the present study is to develop fast automated
      quantification of retinal fluid in optical coherence tomography (OCT) image
      sets.MethodsWe developed an image analysis pipeline tailored towards OCT images
      that consists of five steps for binary retinal fluid segmentation. The method is
      based on feature extraction, pre-segmention, dimension reduction procedures, and
      supervised learning tools.ResultsFluid identification using our pipeline was
      tested on two separate patient groups: one associated to neovascular age-related
      macular degeneration, the other showing diabetic macular edema. For training and
      evaluation purposes, retinal fluid was annotated manually in each cross-section
      by human expert graders of the Vienna Reading Center. Compared with the manual
      annotations, our pipeline yields good quantification, visually and in
      numbers.ConclusionsBy demonstrating good automated retinal fluid quantification,
      our pipeline appears useful to expert graders within their current grading
      processes. Owing to dimension reduction, the actual learning part is fast and
      requires only few training samples. Hence, it is well-suited for integration into
      actual manufacturer's devices, further improving segmentation by its use in daily
      clinical life.

PMID- 28430182
TI  - Evolution of choroidal thickness over time and effect of early and sustained
      therapy in birdshot retinochoroiditis.
AB  - PurposeTo follow choroidal thickness (ChT) over time in birdshot
      retinochoroiditis (BRC) using enhanced depth imaging optical coherence tomography
      (EDI-OCT) and study the effect of early and sustained treatment on ChT.Patients
      and methodsEighteen patients were included and EDI-OCT measurements of ChT were
      analyzed retrospectively in five groups of patients with follow-up times ranging
      from 1 year to >=15 years. The OCT images were evaluated and ChT was calculated
      under the foveola and 1500 MUm temporal, nasal, superior, and inferior to the
      foveola. To assess the effect of treatment, 13 patients with a disease duration
      >=10 years were divided into two groups depending on their treatment status:
      early and sustained therapy vs insufficient, late, or no treatment. ChT was
      compared in these two groups along with the number of typical fundus BRC
      lesions.ResultsThe ChT decreased (r=-0.41, P=0.0018) over the disease duration,
      which ranged from <1 year to >=15 years. In patients with a disease duration >=10
      years, a significant difference in ChT was noted between adequately and
      undertreated patients (288.3+/-76.9 MUm vs 161.4+/-39.2 MUm; P=0.004). At the
      last follow-up, in the group with insufficient therapy 10 of 11 eyes presented
      typical fundus BRC lesions vs 2 of 13 eyes in the treated group (P<=0.0006, F
      test).ConclusionsChoroidal thickness decreases significantly over time in BRC. If
      undertreated, patients show thinner choroids compared with adequately treated
      individuals and present significantly more BRC lesions.

PMID- 28430183
TI  - Neuroprotectin D1 upregulates Iduna expression and provides protection in
      cellular uncompensated oxidative stress and in experimental ischemic stroke.
AB  - Ring finger protein 146 (Iduna) facilitates DNA repair and protects against cell
      death induced by NMDA receptor-mediated glutamate excitotoxicity or by cerebral
      ischemia. Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid
      mediator, promotes cell survival under uncompensated oxidative stress (UOS). Our
      data demonstrate that NPD1 potently upregulates Iduna expression and provides
      remarkable cell protection against UOS. Iduna, which was increased by the lipid
      mediator, requires the presence of the poly(ADP-ribose) (PAR) sites. Moreover,
      astrocytes and neurons in the penumbra display an enhanced abundance of Iduna,
      followed by remarkable neurological protection when DHA, a precursor of NPD1, is
      systemically administered 1 h after 2 h of ischemic stroke. These findings
      provide a conceptual advancement for survival of neural cells undergoing
      challenges to homeostasis because a lipid mediator, made 'on demand,' modulates
      the abundance of a critically important protein for cell survival.

PMID- 28430184
TI  - The ubiquitin ligase LIN41/TRIM71 targets p53 to antagonize cell death and
      differentiation pathways during stem cell differentiation.
AB  - Rapidity and specificity are characteristic features of proteolysis mediated by
      the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the
      remodeling of the embryonic stem cell proteome during the transition from
      pluripotent to differentiated states and its inverse, the generation of inducible
      pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3
      ubiquitin ligases to be linked to stem cell pluripotency and reprogramming.
      Initially discovered in C. elegans as a downstream target of the let-7 miRNA,
      LIN41 is now recognized as a critical regulator of stem cell fates as well as the
      timing of neurogenesis. Despite being indispensable for embryonic development and
      neural tube closure in mice, the underlying mechanisms for LIN41 function in
      these processes are poorly understood. To better understand the specific
      contributions of the E3 ligase activity for the stem cell functions of LIN41, we
      characterized global changes in ubiquitin or ubiquitin-like modifications using
      Lin41-inducible mouse embryonic stem cells. The tumor suppressor protein p53 was
      among the five most strongly affected proteins in cells undergoing neural
      differentiation in response to LIN41 induction. We show that LIN41 interacts with
      p53, controls its abundance by ubiquitination and antagonizes p53-dependent pro
      apoptotic and pro-differentiation responses. In vivo, the lack of LIN41 is
      associated with upregulation of Grhl3 and widespread caspase-3 activation, two
      downstream effectors of p53 with essential roles in neural tube closure. As Lin41
      deficient mice display neural tube closure defects, we conclude that LIN41 is
      critical for the regulation of p53 functions in cell fate specification and
      survival during early brain development.

PMID- 28430185
TI  - Phospholipase Cdelta1 regulates p38 MAPK activity and skin barrier integrity.
AB  - Keratinocytes undergo a unique type of programmed cell death known as
      cornification, which leads to the formation of the stratum corneum (SC), the main
      physical barrier of the epidermis. A defective epidermal barrier is a hallmark of
      the two most common inflammatory skin disorders, psoriasis, and atopic
      dermatitis. However, the detailed molecular mechanisms of skin barrier formation
      are not yet fully understood. Here, we showed that downregulation of
      phospholipase C (PLC) delta1, a Ca2+-mobilizing and phosphoinositide-metabolizing
      enzyme abundantly expressed in the epidermis, impairs the barrier functions of
      the SC. PLCdelta1 downregulation also impairs localization of tight junction
      proteins. Loss of PLCdelta1 leads to a decrease in intracellular Ca2+
      concentrations and nuclear factor of activated T cells activity, along with
      hyperactivation of p38 mitogen-activated protein kinase (MAPK) and inactivation
      of RhoA. Treatment with a p38 MAPK inhibitor reverses the barrier defects caused
      by PLCdelta1 downregulation. Interestingly, this treatment also attenuates
      psoriasis-like skin inflammation in imiquimod-treated mice. These findings
      demonstrate that PLCdelta1 is essential for epidermal barrier integrity. This
      study also suggests a possible link between PLCdelta1 downregulation, p38 MAPK
      hyperactivation, and barrier defects in psoriasis-like skin inflammation.

PMID- 28430186
TI  - Independence of nutrient limitation and carbon dioxide impacts on the Southern
      Ocean coccolithophore Emiliania huxleyi.
AB  - Future oceanic conditions induced by anthropogenic greenhouse gas emissions
      include warming, acidification and reduced nutrient supply due to increased
      stratification. Some parts of the Southern Ocean are expected to show rapid
      changes, especially for carbonate mineral saturation. Here we compare the
      physiological response of the model coccolithophore Emiliania huxleyi (strain
      EHSO 5.14, originating from 50oS, 149oE) with pH/CO2 gradients (mimicking ocean
      acidification ranging from 1 to 4 * current pCO2 levels) under nutrient-limited
      (nitrogen and phosphorus) and -replete conditions. Both nutrient limitations
      decreased per cell photosynthesis (particulate organic carbon (POC) production)
      and calcification (particulate inorganic carbon (PIC) production) rates for all
      pCO2 levels, with more than 50% reductions under nitrogen limitation. These
      impacts, however, became indistinguishable from nutrient-replete conditions when
      normalized to cell volume. Calcification decreased three-fold and linearly with
      increasing pCO2 under all nutrient conditions, and was accompanied by a smaller
      ~30% nonlinear reduction in POC production, manifested mainly above 3 * current
      pCO2. Our results suggest that normalization to cell volume allows the major
      impacts of nutrient limitation (changed cell sizes and reduced PIC and POC
      production rates) to be treated independently of the major impacts of increasing
      pCO2 and, additionally, stresses the importance of including cell volume
      measurements to the toolbox of standard physiological analysis of
      coccolithophores in field and laboratory studies.

PMID- 28430187
TI  - Poorly known microbial taxa dominate the microbiome of permafrost thaw ponds.
AB  - In the transition zone of the shifting permafrost border, thaw ponds emerge as
      hotspots of microbial activity, processing the ancient carbon freed from the
      permafrost. We analyzed the microbial succession across a gradient of recently
      emerged to older ponds using three molecular markers: one universal, one
      bacterial and one fungal. Age was a major modulator of the microbial community of
      the thaw ponds. Surprisingly, typical freshwater taxa comprised only a small
      fraction of the community. Instead, thaw ponds of all age classes were dominated
      by enigmatic bacterial and fungal phyla. Our results on permafrost thaw ponds
      lead to a revised perception of the thaw pond ecosystem and their microbes, with
      potential implications for carbon and nutrient cycling in this increasingly
      important class of freshwaters.

PMID- 28430188
TI  - Interactions between soil- and dead wood-inhabiting fungal communities during the
      decay of Norway spruce logs.
AB  - We investigated the interaction between fungal communities of soil and dead wood
      substrates. For this, we applied molecular species identification and stable
      isotope tracking to both soil and decaying wood in an unmanaged boreal Norway
      spruce-dominated stand. Altogether, we recorded 1990 operational taxonomic units,
      out of which more than 600 were shared by both substrates and 589 were found to
      exclusively inhabit wood. On average the soil was more species-rich than the
      decaying wood, but the species richness in dead wood increased monotonically
      along the decay gradient, reaching the same species richness and community
      composition as soil in the late stages. Decaying logs at all decay stages locally
      influenced the fungal communities from soil, some fungal species occurring in
      soil only under decaying wood. Stable isotope analyses suggest that mycorrhizal
      species colonising dead wood in the late decay stages actively transfer nitrogen
      and carbon between soil and host plants. Most importantly, Piloderma
      sphaerosporum and Tylospora sp. mycorrhizal species were highly abundant in
      decayed wood. Soil- and wood-inhabiting fungal communities interact at all decay
      phases of wood that has important implications in fungal community dynamics and
      thus nutrient transportation.

PMID- 28430189
TI  - Warming enhances old organic carbon decomposition through altering functional
      microbial communities.
AB  - Soil organic matter (SOM) stocks contain nearly three times as much carbon (C) as
      the atmosphere and changes in soil C stocks may have a major impact on future
      atmospheric carbon dioxide concentrations and climate. Over the past two decades,
      much research has been devoted to examining the influence of warming on SOM
      decomposition in topsoil. Most SOM, however, is old and stored in subsoil. The
      fate of subsoil SOM under future warming remains highly uncertain. Here, by
      combining a long-term field warming experiment and a meta-analysis study, we
      showed that warming significantly increased SOM decomposition in subsoil. We also
      showed that a decade of warming promoted decomposition of subsoil SOM with
      turnover times of decades to millennia in a tall grass prairie and this effect
      was largely associated with shifts in the functional gene structure of microbial
      communities. By coupling stable isotope probing with metagenomics, we found that
      microbial communities in warmed soils possessed a higher relative abundance of
      key functional genes involved in the degradation of organic materials with
      varying recalcitrance than those in control soils. These findings suggest warming
      may considerably alter the stability of the vast pool of old SOM in subsoil,
      contributing to the long-term positive feedback between the C cycle and climate.

PMID- 28430190
TI  - Tuning underwater adhesion with cation-pi interactions.
AB  - Cation-pi interactions drive the self-assembly and cohesion of many biological
      molecules, including the adhesion proteins of several marine organisms. Although
      the origin of cation-pi bonds in isolated pairs has been extensively studied, the
      energetics of cation-pi-driven self-assembly in molecular films remains
      uncharted. Here we use nanoscale force measurements in combination with solid
      state NMR spectroscopy to show that the cohesive properties of simple aromatic-
      and lysine-rich peptides rival those of the strong reversible intermolecular
      cohesion exhibited by adhesion proteins of marine mussel. In particular, we show
      that peptides incorporating the amino acid phenylalanine, a functional group that
      is conspicuously sparing in the sequences of mussel proteins, exhibit reversible
      adhesion interactions significantly exceeding that of analogous mussel-mimetic
      peptides. More broadly, we demonstrate that interfacial confinement fundamentally
      alters the energetics of cation-pi-mediated assembly: an insight that should
      prove relevant for diverse areas, which range from rationalizing biological
      assembly to engineering peptide-based biomaterials.

PMID- 28430191
TI  - Activating lattice oxygen redox reactions in metal oxides to catalyse oxygen
      evolution.
AB  - Understanding how materials that catalyse the oxygen evolution reaction (OER)
      function is essential for the development of efficient energy-storage
      technologies. The traditional understanding of the OER mechanism on metal oxides
      involves four concerted proton-electron transfer steps on metal-ion centres at
      their surface and product oxygen molecules derived from water. Here, using in
      situ 18O isotope labelling mass spectrometry, we provide direct experimental
      evidence that the O2 generated during the OER on some highly active oxides can
      come from lattice oxygen. The oxides capable of lattice-oxygen oxidation also
      exhibit pH-dependent OER activity on the reversible hydrogen electrode scale,
      indicating non-concerted proton-electron transfers in the OER mechanism. Based on
      our experimental data and density functional theory calculations, we discuss
      mechanisms that are fundamentally different from the conventional scheme and show
      that increasing the covalency of metal-oxygen bonds is critical to trigger
      lattice-oxygen oxidation and enable non-concerted proton-electron transfers
      during OER.

PMID- 28430192
TI  - A monodisperse transmembrane alpha-helical peptide barrel.
AB  - The fabrication of monodisperse transmembrane barrels formed from short synthetic
      peptides has not been demonstrated previously. This is in part because of the
      complexity of the interactions between peptides and lipids within the hydrophobic
      environment of a membrane. Here we report the formation of a transmembrane pore
      through the self-assembly of 35 amino acid alpha-helical peptides. The design of
      the peptides is based on the C-terminal D4 domain of the Escherichia coli
      polysaccharide transporter Wza. By using single-channel current recording, we
      define discrete assembly intermediates and show that the pore is most probably a
      helix barrel that contains eight D4 peptides arranged in parallel. We also show
      that the peptide pore is functional and capable of conducting ions and binding
      blockers. Such alpha-helix barrels engineered from peptides could find
      applications in nanopore technologies such as single-molecule sensing and nucleic
      acid sequencing.

PMID- 28430193
TI  - Self-propelled supramolecular nanomotors with temperature-responsive speed
      regulation.
AB  - Self-propelled catalytic micro- and nanomotors have been the subject of intense
      study over the past few years, but it remains a continuing challenge to build in
      an effective speed-regulation mechanism. Movement of these motors is generally
      fully dependent on the concentration of accessible fuel, with propulsive movement
      only ceasing when the fuel consumption is complete. Here we report a
      demonstration of control over the movement of self-assembled stomatocyte
      nanomotors via a molecularly built, stimulus-responsive regulatory mechanism. A
      temperature-sensitive polymer brush is chemically grown onto the nanomotor,
      whereby the opening of the stomatocytes is enlarged or narrowed on temperature
      change, which thus controls the access of hydrogen peroxide fuel and, in turn,
      regulates movement. To the best of our knowledge, this represents the first
      nanosized chemically driven motor for which motion can be reversibly controlled
      by a thermally responsive valve/brake. We envision that such artificial
      responsive nanosystems could have potential applications in controllable cargo
      transportation.

PMID- 28430194
TI  - Engineering genetic circuit interactions within and between synthetic minimal
      cells.
AB  - Genetic circuits and reaction cascades are of great importance for synthetic
      biology, biochemistry and bioengineering. An open question is how to maximize the
      modularity of their design to enable the integration of different reaction
      networks and to optimize their scalability and flexibility. One option is
      encapsulation within liposomes, which enables chemical reactions to proceed in
      well-isolated environments. Here we adapt liposome encapsulation to enable the
      modular, controlled compartmentalization of genetic circuits and cascades. We
      demonstrate that it is possible to engineer genetic circuit-containing synthetic
      minimal cells (synells) to contain multiple-part genetic cascades, and that these
      cascades can be controlled by external signals as well as inter-liposomal
      communication without crosstalk. We also show that liposomes that contain
      different cascades can be fused in a controlled way so that the products of
      incompatible reactions can be brought together. Synells thus enable a more
      modular creation of synthetic biology cascades, an essential step towards their
      ultimate programmability.

PMID- 28430195
TI  - A stable compound of helium and sodium at high pressure.
AB  - Helium is generally understood to be chemically inert and this is due to its
      extremely stable closed-shell electronic configuration, zero electron affinity
      and an unsurpassed ionization potential. It is not known to form
      thermodynamically stable compounds, except a few inclusion compounds. Here, using
      the ab initio evolutionary algorithm USPEX and subsequent high-pressure synthesis
      in a diamond anvil cell, we report the discovery of a thermodynamically stable
      compound of helium and sodium, Na2He, which has a fluorite-type structure and is
      stable at pressures >113 GPa. We show that the presence of He atoms causes strong
      electron localization and makes this material insulating. This phase is an
      electride, with electron pairs localized in interstices, forming eight-centre two
      electron bonds within empty Na8 cubes. We also predict the existence of Na2HeO
      with a similar structure at pressures above 15 GPa.

PMID- 28430196
TI  - Organocatalytic stereoselective [8+2] and [6+4] cycloadditions.
AB  - Cycloadditions that involve more than six pi electrons are termed higher-order
      cycloadditions and are an excellent tool for solving complex synthetic
      challenges, as they provide direct access to polycyclic scaffolds that contain
      medium-sized rings. They have interesting synthetic potential for the discovery
      of new bioactive molecules and in natural product synthesis. It is peculiar that
      stereocontrolled [8+2] and [6+4] cycloadditions have been largely neglected for
      the past 50 years. Here we demonstrate a cross-dienamine activation of 2
      cyclopentenone and the unprecedented endocyclic linear-dienamine activation of 2
      cyclohexenones and 2-cycloheptenones. These dienamine intermediates undergo
      aminocatalytic stereoselective [8+2], [6+4] and formal [4+2] cycloadditions with
      various heptafulvenes. The periselectivities of the cycloadditions are controlled
      based on the ring size of the 2-cycloalkenones and the substitution patterns of
      the heptafulvenes. The chiral products obtained undergo various chemical and
      photochemical single-step transformations that give access to other classes of
      all-carbon polycyclic scaffolds.

PMID- 28430198
TI  - Helium Chemistry: React with nobility.

PMID- 28430197
TI  - G-quadruplex organic frameworks.
AB  - Two-dimensional covalent organic frameworks often pi stack into crystalline
      solids that allow precise spatial positioning of molecular building blocks.
      Inspired by the hydrogen-bonded G-quadruplexes found frequently in guanine-rich
      DNA, here we show that this structural motif can be exploited to guide the self
      assembly of naphthalene diimide and perylene diimide electron acceptors end
      capped with two guanine electron donors into crystalline G-quadruplex-based
      organic frameworks, wherein the electron donors and acceptors form ordered,
      segregated pi-stacked arrays. Time-resolved optical and electron paramagnetic
      resonance spectroscopies show that photogenerated holes and electrons in the
      frameworks have long lifetimes and display recombination kinetics typical of
      dissociated charge carriers. Moreover, the reduced acceptors form polarons in
      which the electron is shared over several molecules. The G-quadruplex frameworks
      also demonstrate potential as cathode materials in Li-ion batteries because of
      the favourable electron- and Li-ion-transporting capacity provided by the ordered
      rylene diimide arrays and G-quadruplex structures, respectively.

PMID- 28430200
TI  - Tin can.

PMID- 28430201
TI  - Sending a message to the other side.

PMID- 28430199
TI  - Control over differentiation of a metastable supramolecular assembly in one and
      two dimensions.
AB  - Molecular self-assembly under kinetic control is expected to yield nanostructures
      that are inaccessible through the spontaneous thermodynamic process. Moreover,
      time-dependent evolution, which is reminiscent of biomolecular systems, may occur
      under such out-of-equilibrium conditions, allowing the synthesis of
      supramolecular assemblies with enhanced complexities. Here we report on the
      capacity of a metastable porphyrin supramolecular assembly to differentiate into
      nanofibre and nanosheet structures. Mechanistic studies of the relationship
      between the molecular design and pathway complexity in the self-assembly unveiled
      the energy landscape that governs the unique kinetic behaviour. Based on this
      understanding, we could control the differentiation phenomena and achieve both
      one- and two-dimensional living supramolecular polymerization using an identical
      monomer. Furthermore, we found that the obtained nanostructures are
      electronically distinct, which illustrates the pathway-dependent material
      properties.

PMID- 28430202
TI  - Cation-pi Interactions: Mimicking mussel mechanics.

PMID- 28430204
TI  - Dark times.

PMID- 28430203
TI  - Photoredox activation of carbon dioxide for amino acid synthesis in continuous
      flow.
AB  - Although carbon dioxide (CO2) is highly abundant, its low reactivity has limited
      its use in chemical synthesis. In particular, methods for carbon-carbon bond
      formation generally rely on two-electron mechanisms for CO2 activation and
      require highly activated reaction partners. Alternatively, radical pathways
      accessed via photoredox catalysis could provide new reactivity under milder
      conditions. Here we demonstrate the direct coupling of CO2 and amines via the
      single-electron reduction of CO2 for the photoredox-catalysed continuous flow
      synthesis of alpha-amino acids. By leveraging the advantages of utilizing gases
      and photochemistry in flow, a commercially available organic photoredox catalyst
      effects the selective alpha-carboxylation of amines that bear various functional
      groups and heterocycles. The preliminary mechanistic studies support CO2
      activation and carbon-carbon bond formation via single-electron pathways, and we
      expect that this strategy will inspire new perspectives on using this feedstock
      chemical in organic synthesis.

PMID- 28430205
TI  - Controlled membrane translocation provides a mechanism for signal transduction
      and amplification.
AB  - Transmission and amplification of chemical signals across lipid bilayer membranes
      is of profound significance in many biological processes, from the development of
      multicellular organisms to information processing in the nervous system. In
      biology, membrane-spanning proteins are responsible for the transmission of
      chemical signals across membranes, and signal transduction is often associated
      with an amplified signalling cascade. The ability to reproduce such processes in
      artificial systems has potential applications in sensing, controlled drug
      delivery and communication between compartments in tissue-like constructs of
      synthetic vesicles. Here we describe a mechanism for transmitting a chemical
      signal across a membrane based on the controlled translocation of a synthetic
      molecular transducer from one side of a lipid bilayer membrane to the other. The
      controlled molecular motion has been coupled to the activation of a catalyst on
      the inside of a vesicle, which leads to a signal-amplification process analogous
      to the biological counterpart.

PMID- 28430206
TI  - Transmembrane Signalling: Membrane messengers.

PMID- 28430207
TI  - Corrigendum: Construction and immunogenicity of a recombinant swinepox virus
      expressing a multi-epitope peptide for porcine reproductive and respiratory
      syndrome virus.

PMID- 28430208
TI  - Illumination, data transmission, and energy harvesting: the threefold advantage
      of VLC.
AB  - Visible light communication (VLC) is a promising technology that meets
      illumination and information transmission requirements in an indoor environment.
      Because light waves convey energy, a VLC link may exploit that fact for energy
      harvesting purposes. In this context, a single light emitting diode lamp located
      at a close distance over a tablet or laptop PC can potentially offer simultaneous
      lighting, Internet access, and battery recharging without cables. The present
      study introduces this threefold role of VLC systems by properly adapting some
      energy harvesting receiver architectures recently launched for usage in RF
      communications. The rate-energy trade-off for these architectures is revealed in
      order to maximize the efficiency of simultaneous energy and information
      reception, by elaborating on indicative numerical results. Furthermore, the
      performance in terms of the bit-error rate for pulse amplitude modulated signals
      is investigated. The results obtained offer some useful insights into the
      effective optical receiver implementation from the aspect of information theory.

PMID- 28430209
TI  - Singular skeleton of a Laguerre-Gaussian beam transformed by the double-phase
      ramp converter.
AB  - We analyze transformations of circular Laguerre-Gaussian beams with zero radial
      index after passage through the double-phase-ramp (DPR) converter and study the
      behavior of optical vortices in the propagating transformed beam. Direct and
      inverse DPR converters are considered, and informative features of the complete
      set of optical vortices are revealed. For the input beam with even azimuthal
      index, such a reaction may cause the sign reversal of the axial optical vortex.
      The results can be used for creation of light beams with prescribed singular
      skeleton, for the beam diagnostics, and in high-resolution metrology.

PMID- 28430210
TI  - Folded monocentric imager with deformable mirror focus.
AB  - We describe a catadioptric monocentric imager using an elastic central element
      focused by deformation of a fold mirror. We show the design of 6 mm and 12 mm
      focal length F/2.8 achromats and compare design performance when focusing by
      translating the sensor, translating the fold mirror, and by spherically deforming
      the fold mirror. We tested the 12 mm focal length design using a diamond turned
      polystyrene element as the outer meniscus lens (and mechanical mount), filled
      with an optical gel in contact with the central aperture and fold mirror, and
      demonstrate focusing by mechanical deformation of the fold mirror. The resolution
      at the spherical image surface was inspected by optical relay imaging, yielding a
      best focus MTF50 of 52.6  lp/mm.

PMID- 28430212
TI  - Phase retrieval for attacking fractional Fourier transform encryption.
AB  - An advanced iterative phase retrieval algorithm is applied to perform a
      ciphertext-only attack on the fractional Fourier transform-based double random
      phase encryption system. With the given complex amplitude of ciphertext and
      definite support of the object image, the original object image can be recovered
      by estimating the energy of support area in the recovered image. The encryption
      system can be attacked by analyzing the sensibility of fractional Fourier
      transform order keys and evaluating the energy of the object image support area.
      The proposed algorithm can obtain encrypted fractional order and retrieve two
      random phase keys. Numerical results demonstrate the efficacy of the proposed
      attacking method.

PMID- 28430211
TI  - Compact, high-power, high-beam-quality quasi-CW microsecond five-pass zigzag slab
      1319  nm amplifier.
AB  - We demonstrate a compact, high-power, quasi-continuous-wave (QCW) end-pumped 1319
      nm Nd:YAG slab amplifier laser with good beam quality. The laser is based on a
      QCW pulse Nd:YAG master oscillator and Nd:YAG slab amplifier with multi-pass
      zigzag architecture. The amplifier operates at a pulse repetition frequency of
      500 Hz and pulse width of ~105  MUs, delivering a maximum output power of 51.5 W
      under absorbed pump power of 217.8 W and corresponding to an extraction
      efficiency of 14.2%. The beam quality factor is measured to be Mx2=1.61 and
      My2=1.81 in the orthogonal directions. To the best of our knowledge, this is the
      first compact, high-power, high-beam-quality QCW Nd:YAG amplifier at 1319 nm
      based on a multi-pass zigzag slab structure.

PMID- 28430213
TI  - High peak power hybrid MOPA laser with tunable pulse repetition frequency and
      pulse duration.
AB  - In this paper, we demonstrated a hybrid master oscillator power amplifier (MOPA)
      laser with high peak power and widely tunable pulse repetition frequency (PRF)
      and pulse duration. The first-stage solid-state amplifier was carefully designed
      to keep good beam quality and supply high gain simultaneously. The maximum peak
      power of 760 kW was achieved with average power of 42 W, PRF of 50 kHz, pulse
      duration of 1.1 ns, and near-diffraction limited beam quality. The MOPA laser
      covers a broad tunable temporal range with 1-100 ns for pulse duration and 50 kHz
      1 MHz for PRF. Moreover, we experimentally and numerically figure out that
      Nd:YVO<sub>4</sub> crystal behaves as if continuous-wave (CW) amplification takes
      place when PRF is larger than 30 kHz.

PMID- 28430214
TI  - Globally optimal camera-and-rotation-sensor calibration with a branch-and-bound
      algorithm.
AB  - This paper introduces a globally optimal algorithm for obtaining the rotational
      displacement between the coordinate frames of a rotation sensor and a camera that
      are rigidly attached. Our method minimizes the geometrically meaningful error
      using a branch-and-bound algorithm to find the global solution. For this, we
      derive a bounding inequality and corresponding feasibility problem for a top-down
      efficient search over the rotation space to minimize the L<sub>1</sub>-,
      L<sub>2</sub>-, or L<sub>infinity</sub>-norm error function. Experiments are
      performed with synthetic and real data sets to show the efficacy of the
      algorithm.

PMID- 28430215
TI  - Relationship of the drying process of a corn grain with the thermal emissivity
      and optical interference in the mid infrared range.
AB  - A study of the effect of the thin layer of free water in corn kernels on the
      emissivity and interference in the mid infrared range was performed. The
      emissivity was measured through thermal infrared images by direct method for 8
      days, allowing observance that the thickness of free water modifies the quantity
      of emitted energy and emissivity; however, in the first days when the layer of
      free water is not optically thick the interference caused by the thin film of
      superficial water averts a correct measurement of the emissivity. This
      interference effect was studied and characterized, finding that the number of
      oscillations in the energy of the grain, observed and counted in a very small
      area, can be used to compute the thickness of the free water layer contained
      between the endosperm and the pericarp of the grain.

PMID- 28430216
TI  - Ultrahigh birefringence, ultralow material loss porous core single-mode fiber for
      terahertz wave guidance.
AB  - In this paper, a novel polarization-maintaining single-mode photonic crystal
      fiber (PCF) has been suggested for terahertz (THz) transmission applications. The
      reported PCF has five layers of hexagonal cladding with two layers of porous
      core. The cladding and core territory of the PCF are constituted by circular and
      elliptical air cavities, accordingly acting as a dielectric medium. Different
      geometrical parameters of the proposed PCF including pitches and diameters of
      circular air holes with the major and minor axes of elliptical air cavities being
      varied with the optimized structure. Various effects on the proposed PCF such as
      eccentricity and porosity effects are also carefully investigated. The numerical
      process is investigated by one of the most popular methods, the finite element
      method (FEM). All numerical computational results have revealed the ultrahigh
      birefringence in the order of 1.19*10<sup>-02</sup> as well as the ultralow bulk
      absorption material loss of 0.0689  cm<sup>-1</sup> at the 1 THz activation
      frequency. Besides, the V-parameter is also investigated for checking the
      proposed fiber modality. The proposed single-mode porous core hexagonal PCF is
      expected to be useful for convenient broadband transmission and numerous
      applications in the areas of THz technology.

PMID- 28430217
TI  - Trajectory variations of optical Bloch oscillations for Airy beams in
      transversely and longitudinally modulated photonic lattices.
AB  - We consider four types of modulated photonic lattices and numerically study the
      optical Bloch oscillations of Airy beams in these periodic structures. Our
      results demonstrate that in transversely modulated photonic lattices, the
      oscillation period increases and the amplitude reduces as the separation
      variation index increases. However, the increasing of the width variation index
      could lead to a consistent reduction of oscillation period and amplitude. On the
      other hand, in three kinds of longitudinally bent photonic lattices, the optical
      Bloch oscillation trajectories of Airy beams follow the waveguide shape perfectly
      within the whole propagation length. For another three kinds of refractive index
      longitudinally varied lattices, the optical Bloch oscillation period and
      amplitude are limited with the increasing of refractive index, contributing to
      the presentation of dramatically different Airy propagation trajectories. Our
      study proposes a new view to manipulate the Airy trajectory in periodic
      structures.

PMID- 28430218
TI  - Scattering of one-dimensional Airy beam light sheet with finite energy by a
      sphere.
AB  - A one-dimensional Airy beam light sheet has the advantage of nondiffraction and
      self-reconstruction after encountering particles. The angular scattering of an
      Airy beam by a homogeneous sphere is numerically studied in this paper using Mie
      theory and a plane-wave spectrum method. The effects of sphere radius, refractive
      index, beam width, and sphere position on the angular distribution of scattering
      light are simulated. Correlation coefficients are employed to investigate whether
      Airy beam scattering can be approximated to be plane-wave scattering for
      computational efficiency. The results can be applied in light scattering
      measurement that uses an Airy beam aiming at reducing multiple scattering.

PMID- 28430219
TI  - Method for measuring the area of radiometric apertures using the ratio of
      Gaussian beams.
AB  - I propose and demonstrate a method for determining the area of radiometric
      apertures using the power ratio between Gaussian beams. The result relies on
      measuring the power of an optical beam of known radius with and without the
      radiometric aperture, this with area smaller than the beam spot. The impact of
      the characterization of the laser beam and of the radiometric measurements on the
      area estimation is discussed and a 3-mm in-diameter sample is measured for
      validation. The contactless method is fast and simple and results in a relative
      uncertainty of 0.12% for the sample studied.

PMID- 28430220
TI  - Compound eye and retina-like combination sensor with a large field of view based
      on a space-variant curved micro lens array.
AB  - A compound eye and retina-like combination sensor based on a space-variant curved
      micro lens array (CMLA) is proposed to simultaneously offer the large FOV
      characteristic of a compound eye and retina-like feature of a single aperture
      eye. The mathematical models of the sensor are developed and the structure
      parameters of the space-variant CMLA are deduced. Modeling verification is
      carried out and the results show that the whole field of view (FOV) of the sensor
      is 105 degrees  and the optical information loss rate is 0.06 when the sector is
      32. Imaging simulations illustrate that the sensor possesses the retina-like
      property, i.e., logarithmic-polar transformation. Meanwhile, the simulation
      results indicate that the overlapping angles between the two micro lenses on the
      adjacent rings can be reduced by decreasing the rings and the blind radius, and
      increasing the sectors. This work is beneficial for large FOV and time-efficient
      applications.

PMID- 28430221
TI  - Numerical simulation on the performance analysis of a graphene-coated optical
      fiber plasmonic sensor at anti-crossing.
AB  - A graphene-based surface plasmon resonance sensor using D-shaped fiber in anti
      crossing has been designed. Silver as a plasmon active metal is followed by
      graphene, which helps in preventing oxidation and shows better adsorption
      efficiency to biomolecules. A wavelength interrogation technique based on the
      finite element method has been used to evaluate performance parameters. Design
      parameters such as thickness of silver, residual cladding, and GeO<sub>2</sub>
      dopant concentration have been optimized. The wavelength sensitivity is found to
      be 6800  nm/RIU and resolution of 8.05*10<sup>-5</sup>  RIU. We believe that
      usage of graphene on silver may open a new window for study of online
      biomolecular interaction.

PMID- 28430222
TI  - Impact of partial coherence on the apparent optical transfer function derived
      from the response to amplitude edges.
AB  - We present an investigation of the impact of partial coherence on optical imaging
      systems with the focus on whole slide imaging (WSI) systems for digital
      pathology. The investigation is based on the analysis of the edge response of the
      optical system, which gives rise to an apparent optical transfer function (OTF)
      that can be linked to two elementary complex functions Q and U. The function Q is
      directly related to the transmission cross coefficient (TCC) and can be
      identified with the performance function first introduced by Kintner and
      Sillitto. The function U depends on the TCC in a more involved way. When there
      are no aberrations the Q-function corresponds to the real part of the apparent
      OTF and the U function to the imaginary part of the apparent OTF. Close to the
      incoherent limit the effect of the U function is a mere shift of the edge
      compared to the fully incoherent case. We propose a new expression for the
      dependence of the depth of focus (DOF) on spatial frequency and on the partial
      coherence factor sigma, and validate it by simulation. Partial coherence effects
      are investigated experimentally on a WSI system with a compact LED-based Kohler
      illumination unit with variable condenser NA. This unit incorporates a top hat
      diffuser for providing a reasonably uniform illumination field, with variations
      below 10% across the imaged field of view. The measurements of the apparent
      through-focus OTF derived from edges on a custom resolution chart for different
      sigma were substantially in agreement with the simulations. Finding an optimal
      value for sigma is not straightforward as lateral resolution and the level of
      edge ringing improve with increasing sigma, whereas edge contrast and DOF improve
      with decreasing sigma. We assess that the trade-off for the particular
      application of WSI systems for digital pathology is optimized for a sigma value
      in the range of 0.55-0.75.

PMID- 28430223
TI  - Data processing error analysis based on Doppler asymmetric spatial heterodyne
      measurement.
AB  - The Doppler asymmetric spatial heterodyne (DASH) interferometer provides the
      capability to retrieve wind speed in the upper atmosphere. The data processing
      leads to a significant retrieving error with the development of wind precision.
      The influence of window parameters on the isolated interferogram is analyzed
      theoretically. Based on the derivation, the system is established, and the
      interferogram with a small shift is sampled. The phase and wind speed are
      calculated under various window types and window width values. We conclude that,
      by choosing the Nuttall window with a small width, the wind retrieving error can
      be minimized.

PMID- 28430224
TI  - Spectral shaping for suppressing stimulated-Raman-scattering in a fiber laser.
AB  - We report on the effects of spectral shaping of the output coupler fiber Bragg
      grating (OC-FBG) in a Yb-doped fiber laser on the laser emission spectrum for the
      purpose of inhabiting stimulated Raman scattering (SRS). The lasers with four
      different OC-FBGs were built and characterized. We found that the laser with a
      multiple reflection peak chirped-moire OC-FBG produced a broad laser emission
      linewidth, which, in turn, led to about 100 times lower the SRS emission as
      compared with the laser with a 0.19 nm Gaussian-shaped OC-FBG. A nearly flat-top
      laser output spectrum was obtained from the lasers with a triangle-shaped and
      chirped-moire OC-FBG, respectively.

PMID- 28430225
TI  - Phase shifting by wavelength modulation in a cube beam splitter interferometer.
AB  - A low-cost and fully automated process for phase-shifting interferometry by
      continuously changing the input voltage of a laser diode under the scheme of a
      cube beam splitter interferometer, performing as a two-window common-path
      interferometric setup, is presented. The input signal of a laser diode is
      controlled by a data acquisition device which permits a change in its wavelength
      according to its tunability features. The automation and data analysis is done
      using LabVIEW in combination with MATLAB. By using the Carre algorithm, the phase
      map is obtained. Measurements of visibility and phase shift to verify the phase
      shifting interferometry requirements are also shown.

PMID- 28430226
TI  - Stable nanosecond passively Q-switched all-fiber erbium-doped laser with a 45
      degrees  tilted fiber grating.
AB  - Nanosecond passive Q-switching generation from an all-fiber erbium-doped laser
      with a UV inscribed 45 degrees  tilted fiber grating (TFG) is systematically
      demonstrated. The 45 degrees  TFG is employed as a polarizer together with two
      polarization controllers (PCs) to realize nonlinear polarization rotation (NPR).
      Because of the NPR effect, stable Q-switched pulses with an average output power
      of 17.5 mW, a single pulse energy of 72.7 nJ, a repetition rate of 241 kHz, a
      pulse width of 466 ns, and a signal to noise ratio (SNR) of 58.8 dB are obtained
      with 600 mW pump power. To the best of our knowledge, the SNR is the highest
      among all-fiber passively Q-switched erbium-doped laser. The stability of this
      erbium-doped fiber laser (EDFL) is also examined by monitoring the laser
      consecutively for 5 h under laboratory conditions.

PMID- 28430227
TI  - Digital micromirror device as programmable rough particle in interferometric
      particle imaging.
AB  - The 2D autocorrelation of the projection of an irregular rough particle can be
      estimated using the analysis of its interferometric out-of-focus image. We report
      the development of an experimental setup that creates speckle-like patterns
      generated by "programmable" rough particles of desired-shape. It should become an
      important tool for the development of new setups, configurations, and algorithms
      in interferometric particle imaging.

PMID- 28430228
TI  - Quantum dot semiconductor optical amplifier: role of second excited state on
      ultrahigh bit-rate signal processing.
AB  - In this paper, a theoretical model for a quantum dot semiconductor optical
      amplifier (QDSOA) is proposed. The dynamics of carriers in ground, excited, and
      continuum states and wetting layer are considered in this model. The effects of
      the second excited state (ES2) inclusion are investigated for the first time, to
      the best of our knowledge, in the proposed QDSOA model. Moreover, the
      inhomogeneous broadening effect due to size distribution of dots, and the
      homogeneous broadening effect of a single dot in the gain spectrum by grouping of
      dots based on their optical resonant frequency, are included in the model.
      Furthermore, grouping of photon modes is considered in the model. It is shown
      that improvement of QDSOA performance is possible by considering ES2 in rate
      equations. Gain saturation in different injection currents is obtained for
      various square-shaped pulse train bit-rates. It is shown that carriers'
      relaxation time plays an important role in signal amplification and processing of
      QDSOA. The results illustrate that QDSOA can be used for high bit-rate signal
      processing devices (up to 450 Gbps) with negligible wave distortion and fast gain
      recovery.

PMID- 28430229
TI  - Light scattering from normal and cervical cancer cells.
AB  - The light scattering characteristic plays a very important role in optic imaging
      and diagnostic applications. For optical detection of the cell, cell scattering
      characteristics have an extremely vital role. In this paper, we use the finite
      difference time-domain (FDTD) algorithm to simulate the propagation and
      scattering of light in biological cells. The two-dimensional scattering cell
      models were set up based on the FDTD algorithm. The cell models of normal cells
      and cancerous cells were established, and the shapes of organelles, such as
      mitochondria, were elliptical. Based on these models, three aspects of the
      scattering characteristics were studied. First, the radar cross section (RCS)
      distribution curves of the corresponding cell models were calculated, then
      corresponding relationships between the size and the refractive index of the
      nucleus and light scattering information were analyzed in the three periods of
      cell canceration. The values of RCS increase positively with the increase of the
      nucleo-cytoplasmic ratio in the cancerous process when the scattering angle
      ranges from 0 degrees  to 20 degrees . Second, the effect of organelles in the
      scattering was analyzed. The peak value of the RCS of cells with mitochondria is
      higher than the cells without mitochondria when the scattering angle ranges from
      20 degrees  to 180 degrees . Third, we demonstrated that the influence of cell
      shape is important, and the impact was revealed by the two typical ideal cells:
      round cells and oval cells. When the scattering angle ranges from 0 degrees  to
      80 degrees , the peak values and the frequencies of the appearance of the peaks
      from the two models are roughly similar. It can be concluded that: (1) the size
      of the nuclei and the change of the refractive index of cells have a certain
      impact on light scattering information of the whole cell; (2) mitochondria and
      other small organelles contribute to the cell light scattering characteristics in
      the larger scattering angle area; and (3) the change of the cell shape
      significantly influences the value of scattering peak and the deviation of
      scattering peak position. The results of the numerical simulation will guide
      subsequent experiments and early diagnosis of cervical cancer.

PMID- 28430230
TI  - Compact multichannel high-resolution micro-electro-mechanical systems-based
      interrogator for Fiber Bragg grating sensing.
AB  - We propose a novel type of compact high-resolution multichannel micro-electro
      mechanical systems (MEMS)-based interrogator, where we replace the linear
      detector with a digital micromirror device (DMD). The DMD is typically cheaper
      and has better pixel sampling than an InGaAs detector used in the 1550 nm range,
      which leads to cost reduction and better performance. Moreover, the DMD is a 2D
      array, which means that multichannel systems can be implemented without any
      additional optical components in the interrogator. This makes the proposed
      interrogator highly cost-effective, particularly for multichannel systems. The
      digital nature of the DMD also provides opportunities for advanced programmable
      Hadamard spectroscopy, which, without significant penalties, can greatly improve
      the wavelength fit resolution. Our results show that DMDs can be used in high
      resolution spectroscopy and for Fiber Bragg grating (FBG) interrogation.

PMID- 28430231
TI  - Collimation technique and testing applied to finite size polychromatic sources.
AB  - Highly collimated beams are required in numerous applications and techniques.
      Different methods have been proposed for collimating monochromatic point light
      sources during the recent years. In this work, we analyze how a finite size and
      polychromatic light source can be collimated using only one diffraction grating
      and a CMOS camera placed after the source and the collimating lens. For this, we
      determine the period of the fringes diffracted by the grating and compare it with
      the period of the grating. Analytical equations are obtained to predict the
      amplitude of the fringes and their period. Since self-images disappear for finite
      size polychromatic sources at long distances from the grating, the period has to
      be measured close to the grating. In addition, we give an analytical equation to
      determine the error in the positioning of the source in terms of the source size
      and the setup parameters. Finally, we experimentally corroborate the obtained
      analytical formalism using a white LED of size s=0.6  mm collimated by a lens
      with focal length f=25  mm, and a Ronchi binary grating of period d=250  MUm. In
      this case, we achieve an experimental error in the positioning of the source with
      respect to the focal plane of the lens of deltaz<sub>exp</sub>=92  MUm.

PMID- 28430232
TI  - Phase locking of a mode-locked titanium-sapphire laser-based optical frequency
      comb to a reference laser using a fast piezoelectric actuator.
AB  - We phase lock an octave-spanning optical frequency comb, generated using a mode
      locked titanium-sapphire laser and a photonic-crystal fiber, to a continuous-wave
      laser line-narrowed to a reference cavity. To phase lock the pulse-repetition
      frequency, the cavity length of the mode-locked laser is controlled by using a
      fast piezoelectric-actuated mirror of a servo bandwidth up to 80 kHz. The
      residual phase noise is 0.35 rad, and 89% of the power is concentrated to the
      carrier. To apply the system to optical frequency-ratio measurements and to
      evaluate the phase locking, a simultaneous frequency measurement of the beat
      between the other mode of the comb and another laser line-narrowed to a different
      resonance of the common reference cavity is demonstrated.

PMID- 28430233
TI  - Sensitivity tests on the convergence tendency of the scattering order formulation
      of the discrete dipole approximation.
AB  - In this study, we performed a series of sensitivity tests in order to elucidate
      the convergence tendency of the scattering order formulation (SOF) of the
      discrete dipole approximation (DDA). Using both the original formulation of the
      SOF and a new marching SOF, the progression of orders of scattering marches,
      along with the propagation of the incident plane wave through the scatterer,
      allow dipoles that come into steady-state oscillation with the incident wave
      earlier to more quickly advance to the next order of scattering that is local to
      them. Using the original SOF, we found that for cases in which the simulations
      converge (rods and very small spheres), there are a number of different possible
      convergence tendencies, among them convergence behavior that resembles the
      decaying oscillations of a damped harmonic oscillator. For the cases in which the
      original SOF does not converge, we did not find an indication that the lack of
      convergence is due to a numerical issue, such as round-off error, or that the
      divergence could be alleviated by increasing the dipole resolution or by
      decreasing the size of the marching step in the marching SOF. For cases in which
      the original SOF does not converge, with both the original SOF and the marching
      SOF, we found that the calculated extinction cross section exhibits oscillations
      about the correct value, but with increasing amplitude rather than with
      decreasing amplitude.

PMID- 28430234
TI  - Dimensional properties of Laguerre-Gaussian vortex beams.
AB  - We derive and analyze the dimensional properties of Laguerre-Gaussian vortex
      beams theoretically and numerically. The analytical expressions of inner and
      outer radii are given out and proved to be proportional to the transverse beam
      size, when the topological charge remains. The ratio of the outer and inner
      radius only depends on the topological charge, having nothing to do with the
      waist radius and the propagation distance, and the ratio decreases as the
      topological charge increases. Using a spatial light modulator loaded with
      computer-generated holograms, we generate vortex beams. The experimental results
      are in good agreement with our numerical simulations. This research may provide
      useful insights into the study of the optical vortex beam and its further
      applications.

PMID- 28430235
TI  - Fiber Bragg grating interrogation using wavelength modulated tunable distributed
      feedback lasers and a fiber-optic Mach-Zehnder interferometer.
AB  - This paper demonstrates a technique of high-resolution interrogation of two fiber
      Bragg gratings (FBGs) with flat-topped reflection spectra centered on 1649.55 nm
      and 1530.182 nm with narrow line width tunable semiconductor lasers emitting at
      1651.93 nm and 1531.52 nm, respectively. The spectral shift of the reflection
      spectrum in response to temperature and strain is accurately measured with a
      fiber-optic Mach-Zehnder interferometer that has a free spectral range of 0.0523
      GHz and a broadband photodetector. Laser wavelength modulation and harmonic
      detection techniques are used to transform the gentle edges of the flat-topped
      FBG into prominent leading and trailing peaks that are up to five times narrower
      than the FBG spectrum. Either of these peaks can be used to accurately measure
      spectral shifts of the FBG reflection spectrum with a resolution down to a value
      of 0.47 pm. A digital signal processing board is used to measure the temperature
      induced spectral shifts over the range of 30 degrees C-80 degrees C and strain
      induced spectral shifts from 0  MUepsilon to 12,000  MUepsilon. The shift is
      linear in both cases with a temperature sensitivity of 12.8 pm/ degrees C and
      strain sensitivity of 0.12  pm/MUepsilon. The distinctive feature of this
      technique is that it does not use an optical spectrum analyzer at any stage of
      its design or operation. It can be readily extended to all types of tunable diode
      lasers and is ideally suited for compact field instruments and for biomedical
      applications in stroke rehabilitation monitoring.

PMID- 28430236
TI  - Spectral characterization and discrimination of synthetic fibers with near
      infrared hyperspectral imaging system.
AB  - Synthetic fibers account for about half of all fiber usage, with applications in
      every textile field. The phenomenon of fiber composition not matching the label
      harms consumer interests and impedes market development. Hyperspectral imaging
      technology as a potential technique can be utilized to discriminate mass
      synthetic fibers rapidly and nondestructively and achieves the functions that
      traditional Fourier transform infrared instruments do not have. On the basis of
      investigating the impact of dope-dyeing and wrapping processes on spectra, the
      spectral features (from 900 to 2500 nm) of six categories of synthetic fibers
      were extracted with a hyperspectral imaging system. A principal component
      analysis-linear discriminant analysis model was developed to discriminate the
      chemical content of fibers in different colors and structures, which showed 100%
      discrimination accuracy. Results demonstrated the feasibility of a hyperspectral
      imaging system in synthetic fiber discrimination. Therefore, this method offers a
      more convenient alternative for textile industry on-site discrimination.

PMID- 28430237
TI  - Experimental study of propagation properties of vortex beams in oceanic
      turbulence.
AB  - The intensity of vortex beams always changes on propagation through oceanic
      turbulence, which is influenced by parameters of turbulence. This property is
      usually researched only by numerical simulation. Recently, a new method with a
      spatial light modulator (SLM) can be used in a laboratory to show various
      turbulence, which makes it possible to construct a system of a beam passing
      through turbulence by experiment. We investigate a vortex beam propagating
      through oceanic turbulence with a spiral phase plate and SLM in the laboratory
      and obtain the intensity distribution images by a charge-coupled device. Compared
      with the simulation results, the applicability of this method is more valid.

PMID- 28430238
TI  - Microsensors based on a whispering gallery mode in AlGaN microdisks undercut by
      hydrogen-environment thermal etching.
AB  - AlGaN microdisks were fabricated via a top-down process using electron-beam
      lithography, inductively coupled plasma reactive-ion etching, and hydrogen
      environment thermal etching from commercial epitaxial wafers with a 100-300 nm
      thick AlGaN layer grown on a c-plane GaN layer by metal-organic chemical vapor
      deposition. The hydrogen-environment thermal etching performed well in
      undercutting the AlGaN microdisks owing to the selective etching for the GaN
      layer. The AlGaN microdisks acted as the whispering gallery mode (WGM) optical
      microresonators, exhibiting sharp resonant peaks in room temperature
      photoluminescence spectra. The evanescent component of the whispering gallery
      mode (WGM) is influenced by the ambient condition of the microdisk, resulting in
      the shift of the resonant peaks. The phenomenon is considered to be used for
      microsensors. Using the WGM in the AlGaN microdisks, we demonstrated microsensors
      and a microsensor system, which can potentially be used to evaluate biological
      and chemical actions in a microscale area in real time.

PMID- 28430239
TI  - Research on intelligent algorithms for amplitude optimization of wavefront
      shaping.
AB  - This paper demonstrates further research on intelligent algorithms of binary
      amplitude optimization for wavefront shaping by numerical simulations. A better
      fitness function of the genetic algorithm (GA) has been presented after a
      comparative analysis of enhancement. With this new discriminant, we have achieved
      a relative enhancement of 0.225, which is higher than the theoretical value
      (0.159). In addition, we have also proposed a kind of modified particle swarm
      optimization algorithm (PSO), which has a higher enhancement than the unmodified
      PSO and a faster convergence speed than the GA. These studies provide remarkable
      insights into future exploration of intelligent algorithms for wavefront shaping.

PMID- 28430240
TI  - Linear frequency-modulated continuous-wave ladar system for synthetic aperture
      imaging.
AB  - A novel and high-efficiency linear frequency-modulated continuous-wave (FMCW)
      ladar system for synthetic aperture imaging is proposed and experimentally
      demonstrated. This novel system generates wide-bandwidth linear FMCW ladar
      signals by employing an electro-optic LiNbO<sub>3</sub>- in-phase and quadrature
      modulator with an effective bias controller. The effectiveness of the proposed
      system is experimentally validated. Optical synthetic aperture images are
      obtained by using two 0.41 cm aperture diameter telescopes at the distance of 1
      km. The resolution of these images can reach to 4 cm. A resolution improvement by
      about 10 times is achieved when compared with the conventional real aperture
      imaging system.

PMID- 28430241
TI  - Probing the germination kinetics of ethanol-treated Bacillus thuringiensis
      spores.
AB  - Bacillus thuringiensis (Bt) is the most widely used microbial insecticide. To
      clarify the mechanism of bacterial resistance to ethanol toxicity, the present
      study investigated the effects of 70% (v/v) ethanol at a moderate temperature (65
      degrees C) on Bt spore germination by single-cell Raman spectroscopy and
      differential interference contrast microscopy. We found that over 80% of Bt
      spores were inviable after 30 min of treatment. Moreover, ethanol treatment
      affected spore germination; the time for initiation of rapid calcium dipicolinate
      (CaDPA) release (i.e., lag time, T<sub>lag</sub>), time taken for rapid CaDPA
      release (i.e., DeltaT<sub>release</sub>), and time required for complete
      hydrolysis of the peptidoglycan cortex of spores (i.e., DeltaT<sub>lys</sub>)
      were increased with longer treatment times. Alanine-initiated germination upon
      ethanol treatment for 30-90 min showed a 2- to 4-fold longer T<sub>lag</sub>, 2-
      to 3.5-fold longer DeltaT<sub>release</sub>, and ~2-fold longer
      DeltaT<sub>lys</sub> relative to the control. Dodecylamine-initiated germination
      treated for 15-30 min had 3- to 5-fold longer T<sub>lag</sub> and 1.4- to 1.7
      fold longer DeltaT<sub>release</sub> than the control. Germination induced by
      exogenous CaDPA was observed only in a small fraction of spores treated with
      ethanol for 5 min. Single-cell Raman spectroscopy revealed that more than 52% of
      spores lost CaDPA after 30 min of ethanol treatment; these showed reductions in
      the intensity of 1280 and 1652  cm<sup>-1</sup> bands (corresponding to protein
      alpha-helical structure) and increases in that of 1245 and 1665  cm<sup>-1</sup>
      bands (attributed to irregularities in protein structure). These results indicate
      that CaDPA in the core of Bt spores confers resistance to ethanol, and that
      damage to the spore inner membrane by ethanol treatment results in CaDPA leakage.
      Additionally, moderate-temperature ethanol treatment and consequent denaturation
      of germination-related proteins affected spore germination, specifically by
      inactivating the cortex-lytic enzyme CwlJ. Our findings provide a theoretical
      basis for the development of more effective methods for killing spore-forming
      bacteria; microscopy imaging and Raman spectroscopy can provide novel insight
      into the effects of chemical agents on microbial cells.

PMID- 28430242
TI  - Thermally stable WLEDs with excellent luminous properties by screen-printing a
      patterned phosphor glass layer on a microstructured glass plate.
AB  - In order to improve the luminous properties and thermal reliability of white
      light-emitting diodes (WLEDs), we proposed a promising phosphor-in-glass (PiG)
      converter, which was prepared by screen-printing a patterned phosphor glass layer
      on a microstructured glass plate. The patterned layer achieves four-quadrant
      phosphor geometry based on separated yellow
      Y<sub>3</sub>Al<sub>5</sub>O<sub>12</sub>:Ce<sup>3+</sup> (YAG:Ce<sup>3+</sup>)
      and red CaAlSiN<sub>3</sub>:Eu<sup>2+</sup> (CASN:Eu<sup>2+</sup>) phosphor
      parts. Comparison experiments between the patterned PiG with and without a
      microstructure array (MSA) were conducted at different phosphor glass
      thicknesses. Consequently, for the phosphor glass thickness of 75 MUm, the
      luminous efficacy (LE) of the proposed PiG is increased by 12.5% owing to the
      reduction of total internal reflection at the glass-air interface by the MSA, and
      the corresponding correlated color temperature (CCT) and color rendering index
      are 3701 K and 85.1, respectively. Furthermore, the CCT deviations of patterned
      PiG are reduced from 405 to 115 K and 1004 to 548 K by the MSA at the average
      CCTs of 3800 K and 5500 K, respectively. The results demonstrate that the
      proposed PiG converter can improve the LE and angular color uniformity of multi
      component PiG-based WLEDs simultaneously.

PMID- 28430243
TI  - Amplitude versus phase effects in extreme ultraviolet lithography mask scattering
      and imaging.
AB  - It is now well established that extreme ultraviolet (EUV) mask multilayer
      roughness leads to wafer-plane line-width roughness (LWR) in the lithography
      process. Analysis and modeling done to date has assumed, however, that the
      roughness leading to scatter is primarily a phase effect and that the amplitude
      can be ignored. Under this assumption, simple scattering measurements can be used
      to characterize the statistical properties of the mask roughness. Here, we
      explore the implications of this simplifying assumption by modeling the imaging
      impacts of the roughness amplitude component as a function of the balance between
      amplitude and phase induced scatter. In addition to model-based analysis, we also
      use an EUV microscope to compare experimental through focus data to modeling in
      order to assess the actual amount of amplitude roughness on a typical EUV
      multilayer mask. The results indicate that amplitude roughness accounts for less
      than 1% of the total scatter for typical EUV masks.

PMID- 28430244
TI  - Numerical optimization platform for precision glass molding by the simplex
      algorithm.
AB  - Precision glass molding (PGM) can fabricate aspherical lens and irregular optical
      products in a single step, but its applicability is currently limited by the
      thermally induced residual stresses and lens shape derivation after molding. To
      remove this barrier, this paper develops a numerical optimization platform for
      PGM based on a simplex algorithm and finite element simulation. It was found that
      the platform can effectively reduce the residual stress in a molded lens through
      cooling process optimization and minimize the lens shape derivation by die shape
      compensation. The platform established can improve the lens quality by PMG and
      make molded lenses have better quality than those manufactured by ultraprecision
      machining processes.

PMID- 28430245
TI  - Operation of Ho:YAG ultrafast laser inscribed waveguide lasers.
AB  - We report fabrication and operation of multi-watt level waveguide lasers
      utilizing holmium-doped yttrium aluminum garnet (Ho:YAG). The waveguides were
      fabricated using ultrafast laser inscription, which relies on a chirped pulse
      ytterbium fiber laser to create depressed cladding structures inside the
      material. A variety of waveguides were created inside the Ho:YAG samples. We
      demonstrate output powers of ~2  W from both a single-mode 50 MUm waveguide laser
      and a multimode 80 MUm waveguide laser. In addition, laser action from a co-doped
      Yb:Ho:YAG sample under in-band pumping conditions was demonstrated.

PMID- 28430246
TI  - Method of calculation of internal parameters of liquid lens.
AB  - This paper is focused on the problem of determination of internal parameters of a
      fluidic lens composed of two immiscible liquids of different refractive index,
      which form a tunable refractive interface for changing the focal length of a
      lens. Formulas are derived for calculation of a radius of curvature of the
      internal interface between two liquids and refractive indices of liquids using
      the measurements of the focal length of the lens, positions of focal points, and
      transverse spherical aberration of the lens.

PMID- 28430247
TI  - Precise calibration of pupil images in pyramid wavefront sensor.
AB  - The pyramid wavefront sensor (PWFS) is a novel wavefront sensor with several
      inspiring advantages compared with Shack-Hartmann wavefront sensors. The PWFS
      uses four pupil images to calculate the local tilt of the incoming wavefront.
      Pupil images are conjugated with a telescope pupil so that each pixel in the
      pupil image is diffraction-limited by the telescope pupil diameter, thus the
      sensing error of the PWFS is much lower than that of the Shack-Hartmann sensor
      and is related to the extraction and alignment accuracy of pupil images. However,
      precise extraction of these images is difficult to conduct in practice. Aiming at
      improving the sensing accuracy, we analyzed the physical model of calibration of
      a PWFS and put forward an extraction algorithm. The process was verified via a
      closed-loop correction experiment. The results showed that the sensing accuracy
      of the PWFS increased after applying the calibration and extraction method.

PMID- 28430248
TI  - Accurate determination of dielectric permittivity of polymers from 75  GHz to 1.6
      THz using both S-parameters and transmission spectroscopy.
AB  - Interactions of terahertz (THz) electromagnetic radiation with polymer materials
      have been studied recently with increasing depth and breadth, for purposes of
      both using polymers in fabricating THz optical components such as lenses,
      waveplates, waveguides, and sample holders/containers, and employing THz spectral
      imaging as a new tool for nondestructive testing of polymer composite structures.
      Either endeavor cannot even begin without a quantitative knowledge of the complex
      dielectric permittivity, i.e., the propagation and attenuation properties of such
      polymers in the requisite wave band. In this paper, a number of non-polar and non
      magnetic polymers, such as polytetrafluoroethylene, polypropylene, high-density
      polyethylene, and polymethyl methacrylate, are studied for the purpose of
      determining their complex dielectric permittivity, including its real part and
      imaginary parts, in the wide frequency band from millimeter wave to THz wave (75
      GHz-1.6 THz), in two ways. The first is a free space method based on a vector
      network analyzer covering the frequency region from 75 to 500 GHz, and the second
      is the THz time-domain spectroscopy (THz-TDS), effective for the region of 100
      GHz-1.6 THz. The results are consistent with existing data (with discrepancies
      less than 1% in most cases for both the index of refraction and the absorption
      coefficient), and where they overlap in frequency coverage, the two methods yield
      identical results to within measurement error.

PMID- 28430249
TI  - Study of a reflection grating used in Littrow mount.
AB  - The near and far fields of a finite conductivity metallic grating with
      symmetrical triangular facets, used in Littrow mount, are studied. A new Green's
      function approach, based on the Hertz vector, is introduced and used to propagate
      throughout a two-dimensional domain. The field quantity of primary interest is
      Poynting's vector; however, the stored power is also calculated. In assessing the
      fields generated by the propagator, a quasi-periodic dependence of output
      characteristics on the grating depth to period ratio, discussed in the
      literature, is also found in the present study. With a plane wave incident on the
      grating, geometrical relationships between the incident wave vector and the
      grating surfaces have interesting consequences.

PMID- 28430250
TI  - Tolerancing the alignment of large-core optical fibers, fiber bundles and light
      guides using a Fourier approach.
AB  - Optical fiber technology is found in a wide variety of applications to flexibly
      relay light between two points, enabling information transfer across long
      distances and allowing access to hard-to-reach areas. Large-core optical fibers
      and light guides find frequent use in illumination and spectroscopic
      applications, for example, endoscopy and high-resolution astronomical
      spectroscopy. Proper alignment is critical for maximizing throughput in optical
      fiber coupling systems; however, there currently are no formal approaches to
      tolerancing the alignment of a light-guide coupling system. Here, we propose a
      Fourier alignment sensitivity (FAS) algorithm to determine the optimal tolerances
      on the alignment of a light guide by computing the alignment sensitivity. The
      algorithm shows excellent agreement with both simulated and experimentally
      measured values and improves on the computation time of equivalent ray-tracing
      simulations by two orders of magnitude. We then apply FAS to tolerance and
      fabricate a coupling system, which is shown to meet specifications, thus
      validating FAS as a tolerancing technique. These results indicate that FAS is a
      flexible and rapid means to quantify the alignment sensitivity of a light guide,
      widely informing the design and tolerancing of coupling systems.

PMID- 28430251
TI  - Development of an x-ray eight-image Kirkpatrick-Baez diagnostic system for
      China's laser fusion facility.
AB  - This article presents the development of an x-ray eight-image Kirkpatrick-Baez
      diagnostic system to be used at China's Shenguang-III (SG-III) laser facility in
      aspects of the optical design, multilayers, and online/offline tests. Six pieces
      of concave spherical substrates are used for constituting a special optical
      structure. Dual-periodic tungsten/carbon (W/C) multilayers are used for high
      reflectivity and large angular bandwidth of ~0.1 degrees . The global spatial
      resolution is ~5  MUm in the +/-100  MUm range. The schemes of system
      installation, transport, collimation, and image acquisition at China's SG-III
      facility are also discussed.

PMID- 28430252
TI  - Measuring spatiotemporal ultrafast field structures of pulses from multimode
      optical fibers.
AB  - Ultrashort pulses emerging from multimode optical fibers are spatiotemporally
      complex, because inside these fibers the modes have different spatial intensity
      patterns and experience different propagation velocities and dispersions. To
      determine the spatiotemporal field from multimode fibers, we applied a technique
      for the complete measurement of the output pulses called a spatially and
      temporally resolved intensity and phase evaluation device: full information from
      a single hologram. It yields the complete electric field over space and time from
      multiple digital holograms, simultaneously recorded at different frequencies on a
      single camera frame. Using femtosecond pulses from a Ti:sapphire laser, we
      measured the first few linearly polarized modes (LP<sub>01</sub>,
      LP<sub>11</sub>, LP<sub>02</sub>, and LP<sub>21</sub>) inside several few-mode
      fibers. We also generate movies displaying the measured spatial, temporal, and
      spectral field features.

PMID- 28430253
TI  - Nanoscale Schottky contact surface plasmon "point detectors" for optical beam
      scanning applications.
AB  - We propose and investigate a Schottky contact detector where the contact metal is
      a nanoscale metal stripe waveguide supporting surface plasmons with strong
      localization along the Schottky contact. We consider Au for the metal stripe, p
      doped silicon for the semiconductor, operation in the infrared (at
      lambda<sub>0</sub>=1550  nm), and internal photoemission as the sub-bandgap
      detection mechanism. We find that the main surface plasmon mode of operation of
      the Au stripe exhibits diverging real and imaginary parts of n<sub>eff</sub> with
      decreasing stripe dimensions, commensurate with increasing confinement. The mode
      fields are tightly confined to the immediate vicinity of the stripe within a very
      small area. Coupling efficiencies, responsivities, dark currents, and minimum
      detectable powers are computed. An application envisaged for such nanoscale
      "point detectors" is optical beam scanning, motivated by the very small area of
      the photodetector stripe mode relative to, e.g., a Gaussian beam (~500* smaller),
      such that its field distribution approximates a Dirac delta function in
      comparison, and by the photocurrent originating primarily from selective
      absorption of the photodetector stripe mode. The proposed application was
      verified through numerical simulation, demonstrating that a nanoscale "point
      detector" can scan a tightly focused Gaussian beam (2.5 MUm diameter at
      lambda<sub>0</sub>=1550  nm) with good resolution and signal to noise.

PMID- 28430254
TI  - Lensless wide-field single-shot imaging through turbid media based on object
      modulated speckles.
AB  - The need to image objects through light-scattering materials is common in a range
      of applications. Different methods have been investigated to acquire the image of
      the object when diffusers are presented. In this paper, we demonstrate the object
      reconstruction with single-shot imaging based on the correlography principle and
      phase retrieval algorithm with coherent illumination. We prove the possibility of
      reconstructing positive and negative objects in both transmission and reflection
      modes with collimated and scattered light. Formulas for calculating the size of
      the object from the reconstructed image are presented. We also prove that the
      object can be retrieved from a small section of the raw speckle image. These
      interesting features will have broad potential applications in many areas (such
      as biomedicine, security and sensing).

PMID- 28430255
TI  - Widely tunable 2  MUm continuous-wave and mode-locked fiber laser.
AB  - We propose and experimentally demonstrate a widely tunable mode-locked thulium
      doped fiber laser. The laser can operate at both continuous-wave and mode-locked
      states at different pump power levels. A classic nonlinear polarization rotation
      structure is employed to obtain the passive mode-locked laser. A birefringence
      Lyot filter as a fiber comb filter is used to expand the tuning range. Thanks to
      the filtering component, the tuning range of the continuous-wave laser can reach
      127 nm (1823-1950 nm). The tuning ranges of the single-wavelength and dual
      wavelength mode-locked lasers are 94 nm (1835-1929 nm) and 87 nm (1831-1918 nm),
      respectively, with a 3.085 MHz repetition rate and 75 ps pulse width.

PMID- 28430256
TI  - All-fiber-optic acoustic sensor array for real-time sound source localization.
AB  - Real-time sound source localization has been widely realized by the conventional
      microphone array for the present. In addition, fiber-optic microphones have many
      advantages over conventional microphones. In the present work, an all-fiber-optic
      acoustic array system with a wavelength-division multiplexing scheme is proposed,
      which has a high sensitivity and significant superiority in high-frequency signal
      detection and can be applied in harsh environments. The system also has the
      advantages of simple construction and low cost. Real-time sound source
      localization is realized through the system.

PMID- 28430257
TI  - Optical pressure and numerical simulation of optical forces.
AB  - Optical forces on a particle can be calculated using numerical methods and by
      integrating the Maxwell stress tensor over the surface of the particle. It is
      shown that this gives considerable numerical noise for the radiation force on
      particles with refractive index close to that of the surrounding medium and that
      a large number of mesh elements are necessary. It is found preferable to
      calculate the force from the local optical pressure, as this gives considerably
      less noise and requires significantly fewer mesh elements. Results are also
      compared with an analytical model based on Mie theory.

PMID- 28430258
TI  - Transparency measurement of thin films with one-sided optical access using
      fluorescence imaging.
AB  - Optical transparency can be determined by passing light through an object and
      comparing the intensity of the transmitted light with the intensity of the
      incident light. This measurement needs optical access to both sides of the object
      for illumination and measurement. Optical access to both sides of the object may
      be restricted in some situations due to the presence of an opaque obstacle, lack
      of physical access, etc. A novel technique of transmittance measurement is
      presented that is able to determine the transparency of thin-film objects with
      optical access limited to just one side. This method involves mounting the object
      on a fluorescent substrate, illuminating the object at an excitation wavelength,
      and observing the light radiated from the object at the fluorescence wavelength.
      The observed intensity of the light at the fluorescence wavelength is directly
      related to the transmittance of the object at the excitation and fluorescence
      wavelengths. This optical configuration eliminates the spurious effect of
      reflection of the incident light by filtering the excitation wavelength before
      reaching the optical detector. The technique was used to measure the
      transmittance of neutral density filters, which were also measured using a
      conventional transmittance configuration. The difference between the
      transmittance measured using one-sided optical access and the conventional two
      sided configuration was 2.4% or less. As an example of the utility of the one
      sided measurement technique, the transmittance of paper was measured during
      drying, while the paper sample was sandwiched between a woven dryer fabric and a
      heater. The relationship between the optical transmittance of paper and its
      moisture content has been determined previously, and this relationship was used
      to infer the moisture content of the paper during drying. The moisture content
      distribution during the drying process is shown to be spatially correlated with
      the structure of the dryer fabric.

PMID- 28430259
TI  - Impact of assisting atmospheric pressure plasma on the formation of micro- and
      nanoparticles during picosecond-laser ablation of titanium.
AB  - In this work, we investigated the generation of particles during pure laser and
      plasma-assisted laser ablation of titanium. Experiments were performed using a
      NIR picosecond laser at a wavelength of 1030 nm and a pulse duration of 8 ps. For
      plasma-assisted ablation, an atmospheric pressure dielectric barrier discharge
      plasma was applied where the process gas was argon. Quantitative particle
      distributions at sizes from 10 nm to 10 MUm were determined. In addition, we
      evaluated the amount of ablated material via laser scanning microscopy. The
      ablated volume was significantly increased by a factor of 2 to 3 in the case of
      plasma-assisted ablation, depending on the applied laser dose. It is shown that
      the increase in particle volume and number of particles was lower than the
      ablated volume. However, when applying plasma simultaneously, the generation of
      small nanoparticles increases notably by a factor of up to 6.63 at a laser dose
      of 0.7  kJ/mm<sup>2</sup> for particles with a mean diameter of 10 nm. The
      results suggest that even smaller particles than measurable are generated. Hence,
      plasma-assisted laser ablation could enhance the process efficiency, reduce the
      particle agglomeration, and give rise to an increase in generation of
      nanoparticles at the same time.

PMID- 28430260
TI  - Optical performance enhancement of chip-on-board light-emitting diodes through
      ionic wind patterning.
AB  - Due to the total internal reflection at the upper interface of the encapsulation
      layer, the light extraction efficiency (LEE) of chip-on-board packaging light
      emitting diodes is attenuated significantly. It is well known that the LEE can be
      enhanced by patterning the encapsulation layer. In this study, a novel method of
      patterning the encapsulation layer, which is based on the interaction between the
      ionic wind and liquid encapsulation, is proposed and demonstrated. Two kinds of
      encapsulation patterns, namely dual stripe and meniscus, were fabricated
      successfully. Compared with the traditional flat encapsulation structure, dual
      stripe and meniscus patterns enhanced the LEE by 17.78% and 20.48%, respectively.
      Meanwhile, light intensity distributions were observed to be more uniform. The
      proposed encapsulation patterning method demonstrates significantly simplified
      fabrication process and reduced cost.

PMID- 28430261
TI  - Wideband spectrum analysis of ultra-high frequency radio-wave signals due to
      advanced one-phonon non-collinear anomalous light scattering.
AB  - We present a principally new acousto-optical cell providing an advanced wideband
      spectrum analysis of ultra-high frequency radio-wave signals. For the first time,
      we apply a recently developed approach with the tilt angle to a one-phonon non
      collinear anomalous light scattering. In contrast to earlier cases, now one can
      exploit a regime with the fixed optical wavelength for processing a great number
      of acoustic frequencies simultaneously in the linear regime. The chosen rutile
      crystal combines a moderate acoustic velocity with low acoustic attenuation and
      allows us wide-band data processing within GHz-frequency acoustic waves. We have
      created and experimentally tested a 6-cm aperture rutile-made acousto-optical
      cell providing the central frequency 2.0 GHz, frequency bandwidth ~0.52  GHz with
      the frequency resolution about 68.3 kHz, and ~7620 resolvable spots. A similar
      cell permits designing an advanced ultra-high-frequency arm within a recently
      developed multi-band radio-wave acousto-optical spectrometer for astrophysical
      studies. This spectrometer is intended to operate with a few parallel optical
      arms for processing the multi-frequency data flows within astrophysical
      observations. Keeping all the instrument's advantages of the previous schematic
      arrangement, now one can create the highest-frequency arm using the developed
      rutile-based acousto-optical cell. It permits optimizing the performances
      inherent in that arm via regulation of both the central frequency and the
      frequency bandwidth for spectrum analysis.

PMID- 28430262
TI  - Using trademarked and copyrighted images and material: editorial.
AB  - Editor-in-Chief Ron Driggers cautions authors to avoid using trademarked or
      copyrighted content in a journal publication.

PMID- 28430263
TI  - Energetic materials identification by laser-induced breakdown spectroscopy
      combined with artificial neural network.
AB  - In this study, for the first time to the best of our knowledge, a combination of
      the laser-induced breakdown spectroscopy (LIBS) technique and artificial neural
      network (ANN) analysis has been implemented for the identification of energetic
      materials, including TNT, RDX, black powder, and propellant. Also, aluminum,
      copper, inconel, and graphite have been used for more accurate investigation and
      comparison. After the LIBS test and spectrum acquisition on all samples in both
      air and argon ambient, optimized neural networks were designed by LIBS data.
      Based on input data, three ANN algorithms are proposed: the first is fed with the
      whole LIBS spectra in air (ANN1) and the second with the principle component
      analysis (PCA) scores of each spectrum in air (ANN2) and the other with the PCA
      scores of the spectrum in Ar (ANN3). According to the results, error of the
      network is very low in ANN2 and 3 and the best identification and discrimination
      was obtained by ANN3. After these, in order to validate and for more
      investigation of this combined method, we also used Al/RDX standard samples for
      analysis.

PMID- 28430264
TI  - Optimization of excitation of fiber Fabry-Perot tunable filters used in swept
      lasers using a phase-correction method.
AB  - In this paper we investigate a phase-correction method for compensation of the
      nonlinearity of conventional wavelength-swept laser sources based on a fiber
      Fabry-Perot tunable filter as a wavelength selective element. A triangular
      waveform signal is commonly used to drive the filter. We, however, extract the
      zero crossings from the interferograms and modify the shape of the triangular
      signal accordingly. This algorithm was tested for different values of the optical
      path length difference in the interferometer setup. Significant compensation for
      the nonlinearity of the filter was obtained.

PMID- 28430265
TI  - 1.5  kW radially polarized beam irradiated from a FAF CO<sub>2</sub> laser based
      on an intracavity triple-axicon retroreflector and quarter wave phase retarders.
AB  - In this paper, a three folds spatial resonator composed of a triple-axicon
      retroreflector and four pieces of quarter wave phase retarder is demonstrated to
      directly output radially polarized beams in a fast axial flow (FAF)
      CO<sub>2</sub> laser system. The triple-axicon retroreflector serves as the
      azimuthally polarized beams' selective element, and the quarter wave phase
      retarders convert the azimuthally polarized beams to radially polarized beams.
      Finally, a stable 1.5 kW radially polarized beam is generated in this laser
      system.

PMID- 28430266
TI  - Machine learning approach to OAM beam demultiplexing via convolutional neural
      networks.
AB  - Orbital angular momentum (OAM) beams allow for increased channel capacity in free
      space optical communication. Conventionally, these OAM beams are multiplexed
      together at a transmitter and then propagated through the atmosphere to a
      receiver where, due to their orthogonality properties, they are demultiplexed. We
      propose a technique to demultiplex these OAM-carrying beams by capturing an image
      of the unique multiplexing intensity pattern and training a convolutional neural
      network (CNN) as a classifier. This CNN-based demultiplexing method allows for
      simplicity of operation as alignment is unnecessary, orthogonality constraints
      are loosened, and costly optical hardware is not required. We test our CNN-based
      technique against a traditional demultiplexing method, conjugate mode sorting,
      with various OAM mode sets and levels of simulated atmospheric turbulence in a
      laboratory setting. Furthermore, we examine our CNN-based technique with respect
      to added sensor noise, number of photon detections, number of pixels, unknown
      levels of turbulence, and training set size. Results show that the CNN-based
      demultiplexing method is able to demultiplex combinatorially multiplexed OAM
      modes from a fixed set with >99% accuracy for high levels of turbulence-well
      exceeding the conjugate mode demultiplexing method. We also show that this new
      method is robust to added sensor noise, number of photon detections, number of
      pixels, unknown levels of turbulence, and training set size.

PMID- 28430267
TI  - 3D cost aggregation with multiple minimum spanning trees for stereo matching.
AB  - Cost aggregation is one of the key steps in the stereo matching problem. In order
      to improve aggregation accuracy, we propose a cost-aggregation method that can
      embed minimum spanning tree (MST)-based support region filtering into PatchMatch
      3D label search rather than aggregating on fixed size patches. However, directly
      combining PatchMatch label search and MST filtering is not straightforward, due
      to the extremely high complexity. Thus, we develop multiple MST structures for
      cost aggregation on plenty of 3D labels, and design the tree-level random search
      strategy to find possible 3D labels of each pixel. Extensive experiments show
      that our method reaches higher accuracy than the other existing cost-aggregation
      and global-optimization methods such as the 1D MST, the PatchMatch and the
      PatchMatch Filter, and currently ranks first on the Middlebury 3.0 benchmark.

PMID- 28430268
TI  - Controlling the self-folding of a polymer sheet using a local heater: the effect
      of the polymer-heater interface.
AB  - Self-folding of a pre-strained shape memory polymer (SMP) sheet was demonstrated
      using local joule heating. Folding is caused by shrinkage variation across the
      thickness of the SMP sheet. The folding direction can be controlled by the
      interfacial interaction between the heater and the SMP sheet. When the heater is
      placed on the SMP sheet with no constraint (weak interface), the SMP sheet folds
      toward the heater. Temperature gradient across the SMP thickness gives rise to
      the shrinkage variation. By contrast, when the heater is fixed to the SMP sheet
      (strong interface), the SMP sheet can fold away from the heater. In this case
      shrinkage variation is dictated by the constraining effect of the heater. In
      either mode, 180 degrees folding can be achieved. The folding angle can be
      controlled by varying the heater width and folding time. This method is simple
      and can be used to fold structures with sharp angles in a sequential manner. A
      variety of structures were folded as demonstrations, including digital numbers 0
      9, a cube, a boat, and a crane.

PMID- 28430269
TI  - An active catalytic system for Suzuki-Miyaura cross-coupling reactions using low
      levels of palladium loading.
AB  - An easily available Pd(OAc)2/(2-(anthracen-9-yl)-1H-inden-3-yl)
      dicyclohexylphosphine/toluene/iPrOH/water catalytic system was developed, which
      shows high catalytic activity in the Suzuki-Miyaura cross-coupling reactions of a
      diverse array of aryl and heteroaryl chlorides with Pd loadings down to 0.01
      mol%.

PMID- 28430270
TI  - Atomistic non-adiabatic dynamics of the LH2 complex with a GPU-accelerated ab
      initio exciton model.
AB  - We recently outlined an efficient multi-tiered parallel ab initio excitonic
      framework that utilizes time dependent density functional theory (TDDFT) to
      calculate ground and excited state energies and gradients of large supramolecular
      complexes in atomistic detail - enabling us to undertake non-adiabatic
      simulations which explicitly account for the coupled anharmonic vibrational
      motion of all the constituent atoms in a supramolecular system. Here we apply
      that framework to the 27 coupled bacterio-chlorophyll-a chromophores which make
      up the LH2 complex, using it to compute an on-the-fly nonadiabatic surface
      hopping (SH) trajectory of electronically excited LH2. Part one of this article
      is focussed on calibrating our ab initio exciton Hamiltonian using two key
      parameters: a shift delta, which corrects for the error in TDDFT vertical
      excitation energies; and an effective dielectric constant epsilon, which
      describes the average screening of the transition-dipole coupling between
      chromophores. Using snapshots obtained from equilibrium molecular dynamics
      simulations (MD) of LH2, we tune the values of both delta and epsilon through
      fitting to the thermally broadened experimental absorption spectrum, giving a
      linear absorption spectrum that agrees reasonably well with experiment. In part
      two of this article, we construct a time-resolved picture of the coupled
      vibrational and excitation energy transfer (EET) dynamics in the sub-picosecond
      regime following photo-excitation. Assuming Franck-Condon excitation of a narrow
      eigenstate band centred at 800 nm, we use surface hopping to follow a single
      nonadiabatic dynamics trajectory within the full eigenstate manifold. Consistent
      with experimental data, this trajectory gives timescales for B800->B850
      population transfer (tauB800->B850) between 650-1050 fs, and B800 population
      decay (tau800->) between 10-50 fs. The dynamical picture that emerges is one of
      rapidly fluctuating LH2 eigenstates that are delocalized over multiple
      chromophores and undergo frequent crossing on a femtosecond timescale as a result
      of the atomic vibrations of the constituent chromophores. The eigenstate
      fluctuations arise from disorder that is driven by vibrational dynamics with
      multiple characteristic timescales. The scalability of our ab initio excitonic
      computational framework across massively parallel architectures opens up the
      possibility of addressing a wide range of questions, including how specific
      dynamical motions impact both the pathways and efficiency of electronic energy
      transfer within large supramolecular systems.

PMID- 28430271
TI  - Theoretical modulation of singlet/triplet chemiexcitation of chemiluminescent
      imidazopyrazinone dioxetanone via C8-substitution.
AB  - Coelenterazine, a member of the imidazopyrazinone class of chemiluminescent
      substrates, presents significant potential as a dynamic probe of reactive oxygen
      species in a biological environment, such as a superoxide anion, in which these
      species are important in cellular biology and pathology. The objective of the
      current study was to understand in what way the efficiency of singlet and triplet
      chemiexcitation could be modulated, towards a more efficient use of
      imidazopyrazinone-based compounds as dynamic chemiluminescent probes. To this end
      the thermolysis of imidazopyrazinone dioxetanone, substituted at the C8-position
      with electron-donating or electron-withdrawing groups, was characterized with a
      theoretical approach based on density functional theory. Substituents with
      different electron-donating/withdrawing characters have only a limited effect on
      the singlet chemiexcitation of anionic dioxetanone. For neutral dioxetanone, both
      electron-withdrawing and weak electron-donating substituents increase singlet
      chemiexcitation, to the contrary of strong electron-donating groups. During their
      thermolysis reaction, all molecules presented regions of degeneracy with triplet
      states, thereby indicating the possibility of triplet chemiexcitation.

PMID- 28430272
TI  - Molecular rare earth metal alumosilicates.
AB  - The synthesis and stabilization of molecular four-coordinated lanthanide
      alumosilicates was achieved by the use of a highly encumbered alumosilicate
      ligand LAl(OH.thf)(MU-O)Si(OH)(OtBu)2 (1, L = HC{C(Me)N(2,6-iPr2C6H3)}2).
      Reactions between 1 and tris-cyclopentadienyl lanthanides (LnCp3; Ln = Ce, Nd,
      Sm, Gd, Tb, Dy, Y, Er) derived in the isolation of eight compounds (2-9) where
      the ligand is observed in three different bonding modes: adducts (2, 3),
      spirocyclic (4) or cyclic (5-9) coordination compounds. The observed reactivity
      can be related to the ionic radius of the lanthanide atom and the nature of the
      oxygen donor-atom from the hydroxide (Al-OH) or hydroxyl (Si-OH) moieties in 1.
      Compounds 2-9 present general O-Al-O-Si-O-Ln connectivities with different
      degrees of substitution over the -OH groups in 1 and structural features with
      only slight variations over the alumosilicate moiety (O-Al-O-Si-O) upon the
      lanthanide coordination. The spirocyclic samarium derivative presents two tetra
      coordinated samarium atoms with a tetrahedral and distorted square planar
      geometries, respectively, as a result of a highly strained polycyclic
      architecture.

PMID- 28430273
TI  - The interfacing structural effect of Ag/graphene oxide nanohybrid films on
      surface enhanced Raman scattering.
AB  - The interfacing structural effect of Ag/graphene oxide (GO) nanohybrid films on
      SERS was investigated by using Ag nanostructures immobilized on polyallylamine
      hydrochloride (PAA) functionalized-GO and reduced GO (RGO) films. We found that
      the electron transfer from Ag nanostructures to GO derivatives dominantly
      occurred at the interfaces between Ag nanostructures and the sp2 carbon domains
      of GO and RGO films. By utilizing 4-aminothiophenol (4-ATP) as a Raman probe, it
      was revealed that this electron transfer process augmented the enhancement factor
      (EF) of 4-ATP up to ~1.8 fold on Ag/PAA-RGO nanohybrid films compared to Ag/PAA
      GO nanohybrid films with the increasing interfacing area between Ag
      nanostructures and the sp2 carbon domains of GO derivatives through wet-chemical
      processes.

PMID- 28430274
TI  - High-throughput and ultratrace naked-eye colorimetric detection of Au3+ based on
      the gold amalgam-stimulated peroxidase mimetic activity in aqueous solutions.
AB  - Herein, we present a catalysis-based, label-free, and efficient strategy for a
      rapid, high-throughput, highly selective and ultrasensitive naked-eye
      colorimetric assay of Au3+ in aqueous solutions, based on the gold amalgam
      stimulated peroxidase mimetic activity.

PMID- 28430275
TI  - Concave gold bipyramids bound with multiple high-index facets: improved Raman and
      catalytic activities.
AB  - Concave nanocrystals usually exhibit a large electromagnetic-field enhancement
      and superior catalytic performance due to their sharp corners, negative curvature
      and high-index facets. Conventional gold bipyramids (AuBPs) possess intriguing
      plasmonic properties which are attractive for various applications while the
      surface curvature of the reported bipyramids has not been fine-tuned to concave
      or convex structures to date. Additionally, the longitudinal surface plasmon
      resonance (LSPR) wavelengths of conventional AuBPs are mostly located in the
      range of 650-1350 nm and the sizes of these nanoparticles are usually not beyond
      350 nm, which are not facilitated to some nano-focusing and nanophotonic
      applications. Herein, we reported a facile and robust approach for fabricating
      concave AuBPs (CAuBPs) with multiple high-index facets which are distinct from
      the conventional AuBPs and nanojavelin structures. The length of the as-prepared
      CAuBPs can even extend up to 800 nm. The CAuBP nanoparticles exhibit a strikingly
      pronounced broader plasmonic tuning range (even exceeding 1800 nm) and provide
      much higher electromagnetic-field enhancements in comparison to the conventional
      AuBPs, which broaden the promising applications of CAuBPs for many single
      particle analyses. More importantly, the surface-enhanced Raman scattering (SERS)
      signals of CAuBPs on the single-particle or aqueous solution both displayed an
      enhanced intensity compared to conventional AuBPs. The CAuBP nanoparticles also
      exhibited improved catalytic activity due to the incredible abundance of
      uncoordinated atoms as active sites.

PMID- 28430276
TI  - Understanding gas adsorption in MOF-5/graphene oxide composite materials.
AB  - Metal-organic framework (MOF) and graphene oxide (GO) composite materials
      (MOF/GO) have been regarded as promising for separation applications due to their
      synergistically enhanced adsorption properties. Molecular-level understandings of
      these materials, however, remain unknown to date. In this study, molecular
      simulations were used, for the first time, to model these composite materials.
      Specifically, the composite MOF-5/GO material was modeled as stacks of sandwich
      like layers on top of one another, consistent with experimental observations
      inferred from XRD and the SEM images. Simulations indicate that CO2 and CH4 bind
      strongly in the MOF/GO interface region, resulting in synergistically enhanced
      adsorption properties. To exploit the interface region, we found that in
      simulating linear alkanes, larger guest molecules show substantially improved
      adsorption properties in composites compared to the parent MOF-5 structure,
      illustrating that the performance of adsorption in these molecules will benefit
      the most from the MOF/GO composites.

PMID- 28430277
TI  - Rapid single-cell detection and identification of pathogens by using surface
      enhanced Raman spectroscopy.
AB  - For the successful treatment of infections, real-time analysis and enhanced
      multiplex capacity, sensitivity and cost-effectiveness of the developed detection
      method are critical. In this work, surface-enhanced Raman scattering (SERS) was
      employed with the final aim of identification and discrimination of pathogenic
      bacteria, based on their detected SERS fingerprint at the single-cell level.
      Several genera of bacteria that are found in most of the isolated infections in
      bacteraemia were successfully identified in less than 5 minutes without the use
      of antibodies or other specific receptors. The key element of the SERS direct
      detection platform is the SERS substrate, which combines easy production at low
      costs with a high enhancement enabling single-cell detection. The innovative
      approach of detection required the in situ synthesis of silver nanoparticles
      (NPs), ensuring an intimate contact with the bacterial membrane. This protocol
      provided a good reproducibility of the single-cell SERS spectra and was
      successfully applied both on Gram-negative and Gram-positive microorganisms (E.
      coli, M. morganii, E. lactis, L. casei). Thus, a label-free SERS-based biosensor
      for pathogen detection was developed with low costs, minimal sample preparation,
      high-accuracy and a very short analysis time of less than 5 min, which is crucial
      for infection diagnosis.

PMID- 28430278
TI  - Enhanced enzymatic reactions by solar-to-thermal conversion nanoparticles.
AB  - In this study, we show that enzymatic reactions can be easily enhanced by visible
      light irradiation. It is a general method as demonstrated by several different
      types of enzymes, including amylase, cellulase and lipase, which are typically
      utilized in many industrial biocatalysis processes. Markedly different from
      conventional titanium dioxide (TiO2) nanoparticles which absorb UV light and
      generate little thermal energy, defect-rich Magneli phase titanium oxide (Ti8O15)
      nanoparticles absorb solar light and provide a highly effective solar-to-thermal
      conversion, which greatly enhances enzymatic reactions. This accelerating effect,
      together with the biocompatibility, high chemical stability and easy preparation
      of Ti8O15 nanoparticles, makes this method appealing for enhancing the efficiency
      of biocatalysis.

PMID- 28430279
TI  - Microcontact printing with aminosilanes: creating biomolecule micro- and
      nanoarrays for multiplexed microfluidic bioassays.
AB  - Microfluidic systems integrated with protein and DNA micro- and nanoarrays have
      been the most sought-after technologies to satisfy the growing demand for high
      throughput disease diagnostics. As the sensitivity of these systems relies on the
      bio-functionalities of the patterned recognition biomolecules, the primary
      concern has been to develop simple technologies that enable biomolecule
      immobilization within microfluidic devices whilst preserving bio-functionalities.
      To address this concern, we introduce a two-step patterning approach to create
      micro- and nanoarrays of biomolecules within microfluidic devices. First, we
      introduce a simple aqueous based microcontact printing (MUCP) method to pattern
      arrays of (3-aminopropyl)triethoxysilane (APTES) on glass substrates, with
      feature sizes ranging from a few hundred microns down to 200 nm (for the first
      time). Next, these substrates are integrated with microfluidic channels to then
      covalently couple DNA aptamers and antibodies with the micro- and nanopatterned
      APTES. As these biomolecules are covalently tethered to the device substrates,
      the resulting bonds enable them to withstand the high shear stresses originating
      from the flow in these devices. We further demonstrated the flexibility of this
      technique, by immobilizing multiple proteins onto these APTES-patterned
      substrates using liquid-dispensing robots to create multiple microarrays. Next,
      to validate the functionalities of these microfluidic biomolecule microarrays, we
      perform (i) aptamer-based sandwich immunoassays to detect human interleukin 6
      (IL6); and (ii) antibody-based sandwich immunoassays to detect human c-reactive
      protein (hCRP) with the limit of detection at 5 nM, a level below the range
      required for clinical screening. Lastly, the shelf-life potential of these ready
      to-use microfluidic microarray devices is validated by effectively
      functionalizing the patterns with biomolecules up to 3 months post-printing. In
      summary, with a single printing step, this aminosilane patterning technique
      enables the creation of functional microfluidic micro- and nano-biomolecule
      arrays, laying the foundation for high-throughput multiplexed bioassays.

PMID- 28430281
TI  - Insertion of sodium phosphaethynolate, Na[OCP], into a zirconium-benzyne complex.
AB  - Reaction of the zirconium-benzyne complex [Cp2Zr(PMe3)(C6H4)] with sodium
      phosphaethynolate, Na[OCP], affords a zircono-phosphaalkene complex. Notably,
      unlike reactions of other transition metal complexes with Na[OCP] that yield the
      products of simple salt metathesis, this transformation represents novel Na[OCP]
      insertion chemistry and formation of an unusual solid state coordination polymer.
      The polymer is disrupted upon addition of Me3SiCl to afford a silyl-capped dimer
      that retains the zirconophosphaalkene functionality. Protonation of either form
      of zirconophosphaalkenes results in the formation of benzoylphosphine,
      PhC([double bond, length as m-dash]O)PH2.

PMID- 28430280
TI  - Potassium complexes supported by monoanionic tetradentate amino-phenolate
      ligands: synthesis, structure and catalysis in the ring-opening polymerization of
      rac-lactide.
AB  - A series of potassium complexes bearing monoanionic tetradentate amino-phenolate
      ligands, [LK]2 (L = {(2-R1)C6H4CH2N[(CH2)2R2]CH2(4-R4-6-R3)C6H2O-}, R1 = NMe2, R2
      = NEt2, R3 = CPh3, R4 = Me (1); R1 = R2 = NEt2, R3 = CPh3, R4 = Me (2); R1 =
      NMe2, R2 = NEt2, R3 = R4 = cumyl (4); R1 = R2 = OMe, R3 = tBu, R4 = Me (6); L =
      (2-NMe2)C6H4CH2N[[CH2-(S)-1-butylpyrrolidinyl]CH2(4-Me-6-CPh3)C6H2O-] (3)), have
      been synthesized via reactions of KN(SiMe3)2 and 1 equiv. of the corresponding
      aminophenols. The solid-state structures of typical complexes 4 and 6 are
      determined via X-ray diffraction studies, which reveal the dinuclear nature of
      these complexes. By contrast, DOSY measurements of 1, 4 and 6 suggest that these
      complexes are monomeric in solution. It is noteworthy that the coordination
      chemistry of these potassium complexes is versatile, which is closely related to
      the nature of the ortho-substituent of the phenolate ring, as indicated by the
      results of the corresponding spectroscopic studies. In the presence of iPrOH, 1-4
      and 6 could initiate the polymerization of 500 equiv. of rac-lactide to achieve
      high monomer conversions within several minutes but afford atactic PLAs with
      slightly isotactic-enriched microstructures (Pm = 0.58-0.60). Experimental
      results also demonstrated that a bulky trityl substituent at the ortho-position
      of the phenolate ring of the ligand framework is beneficial for the enhancement
      of the activities of these potassium complexes.

PMID- 28430282
TI  - A ratiometric sensor for DNA based on a dual emission Ru(dppz) light-switch
      complex.
AB  - Herein we describe the DNA binding properties of two new water-soluble ruthenium
      complexes; experimental and computational data reveal that both complexes display
      dual emission from MLCT and LLCT excited states. The interaction of the new
      complexes with DNA was also investigated. Although one of the complexes only
      binds DNA though groove binding, the second complex has separate ligands capable
      of groove binding and intercalation. Nevertheless, it was found that both
      complexes interact with duplex DNA with high affinity. DNA induced distinctive
      changes in the emission of the complexes; although the groove binding complex
      only displays a modest increase in emission on binding, the complex that contains
      the intercalating RuII(dppz) moiety displays a large increase in MLCT-based
      emission on DNA binding while emission from the LLCT excited state is unaffected.
      This means that the complex functions as the first ratiometric sensor for DNA.

PMID- 28430283
TI  - Regioisomerically pure multiaryl coronene derivatives: highly efficient synthesis
      via bay-extended perylene tetrabutylester.
AB  - By a facile strategy, we obtained three pure regioisomers of multiaryl coronene
      bisimide (CBI) derivatives via IBr-mediated annelation and subsequent Suzuki
      coupling reactions with high yields. A series of aromatic groups with different
      electron properties were efficiently introduced to obtain functional CBI
      derivatives under mild conditions with good yields. Furthermore, the annelation
      mechanism as well as the optical and electrochemical properties of CBI
      derivatives were further investigated.

PMID- 28430284
TI  - O2-(6-Oxocyclohex-1-en-1-yl)methyl diazen-1-ium-1,2-diolates: a new class of
      nitric oxide donors activatable by GSH/GSTpi with both anti-proliferative and
      anti-metastatic activities against melanoma.
AB  - The new nitric oxide (NO) donor O2-(6-oxocyclohex-1-en-1-yl)methyl diazen-1-ium
      1,2-diolate 3c could simultaneously liberate NO as well as an active 3
      glutathionyl-2-exomethylene-cyclohexanone 2 in the presence of GSH/GSTpi; exhibit
      potent antiproliferative activity; repress migration, invasion, and lateral
      migration of metastatic B16-BL6 cells; and significantly decrease hetero-adhesion
      of B16-BL6 cells to human umbilical vein endothelial cells.

PMID- 28430285
TI  - Electrochemical synthesis of phosphorus-doped graphene quantum dots for free
      radical scavenging.
AB  - In this work, phosphorus-doped graphene quantum dots (P-GQDs) with a high
      phosphorus doping content (>7 at%) are synthesized via an electrochemical
      approach. Sodium phytate (C6H6Na12O24P6), a green food antioxidant additive, is
      used as the electrolyte for providing both a phosphorus source and an
      electrolysis environment. The obtained P-GQDs exhibit excellent scavenging
      activity of free radicals, such as hydroxyl radicals (OH) and 2,2-diphenyl-1
      picrylhydrazyl (DPPH). Combined with Raman, FT-IR, and XPS spectral analyses, the
      reason for high phosphorus content and the mechanism of free radical scavenging
      of P-GQDs are investigated in our work.

PMID- 28430286
TI  - Clinical presentation and outcomes of patients with acute rheumatic fever and
      rheumatic heart disease seen at a tertiary hospital setting in Port Elizabeth,
      South Africa.
AB  - BACKGROUND: The incidence of acute rheumatic fever (ARF) and rheumatic heart
      disease (RHD) has waned in Western countries, however that is not the situation
      in developing nations. METHODS: Records were reviewed of patients from the
      Eastern Cape municipal districts who presented to the Paediatric Cardiology Unit
      with ARF and RHD from January 2008 to August 2015. RESULTS: Total of 56 patients
      with ARF/RHD was reviewed. The majority of patients (n = 52) presented for the
      first time with RHD. Four patients presented with ARF and two had recurrent ARF.
      Six patients presented with a combination of RHD and congenital heart disease.
      Twenty-three patients were operated on for chronic rheumatic valve disease, with
      good outcomes. CONCLUSION: The true burden of ARF/RHD is unknown in the Eastern
      Cape. Prospective studies are needed to accurately determine the prevalence of
      RHD in this province.

PMID- 28430287
TI  - Dysembryoplastic neuroepithelial tumour: insight into the pathology and
      pathogenesis.
AB  - <i>Dysembryoplastic neuroepithelial tumour (DNT) is categorized as a benign
      glioneuronal neoplasm affecting children and young adults with chronic epileptic
      seizures. It is characterized by predominant intracortical localization and
      nodular architecture. Dysembryoplastic neuroepithelial tumour usually
      demonstrates a distinctive morphological pattern with a specific glioneuronal
      element but occasionally, its morphological picture is heterogeneous and
      unspecific. Thus, considering the morphology of DNT, three different
      histopathological subtypes are distinguished: simple, complex, and non-specific
      and diffuse. The DNT lesions are often related with focal cortical dysplasia
      (FCD) type IIIb, which is postulated to play a role in epileptogenicity.
      Moreover, the accompanying inflammation process might be implicated in DNT
      related epileptogenesis. Dysembryoplastic neuroepithelial tumour is generally
      characterized by favourable prognosis and good results of surgical treatment. The
      pathogenesis and molecular mechanisms involved in DNT development remain
      uncertain. The main molecular findings are connected with BRAF alterations and
      activation of RAS/ERK, PI3K/AKT and mTOR signalling pathways. The present review
      summarizes the clinical, histopathological and molecular findings of DNT. The
      classification controversy, morphological heterogeneity and diagnostic problems
      are also discussed. </i>.

PMID- 28430288
TI  - Mesenchymal/proangiogenic factor YKL-40 related to glioblastomas and its
      relationship with the subventricular zone.
AB  - <i>Glioblastoma is the most common primary brain tumor. Despite multimodality
      therapy with aggressive microsurgical resection and adjuvant chemotherapy and
      radiotherapy, the median survival is below 15 months. Glioblastomas are
      heterogeneous tumors with high resistance to most chemotherapeutic drugs.
      According to reliable evidence, YKL-40, one of the best investigated chitinase
      like protein, may facilitate invasion, migration and angiogenesis, and could be
      also responsible for temozolomide resistance in glioblastoma, thus conferring a
      dismal prognosis. Previous studies have demonstrated that glioblastoma stem cells
      give rise to endothelial cells through an YKL-40 influence. Such factor is
      closely related to the subventricular zone. This review focuses on the most
      recent theories involving the possible relationship between topographic
      gliomagenesis related to the subventricular zone and YKL-40.</i>.

PMID- 28430289
TI  - Evidence from spatial pattern analysis for the anatomical spread of alpha
      synuclein pathology in Parkinson's disease dementia.
AB  - <i>The objective of this study was to determine whether there is evidence from
      quantitative morphometry and spatial pattern analysis to support the hypothesis
      of anatomical spread of ?-synuclein in Parkinson's disease dementia (PDD). Hence,
      clustering of ?-synuclein-immunoreactive Lewy bodies (LB), Lewy neurites (LN),
      and Lewy grains (LG) was studied in ?-synuclein-immunolabeled sections of
      cortical and limbic regions in 12 cases of PDD. The data suggested that: (1) LB,
      LN, and LG occurred in clusters which in 63% of regions were regularly
      distributed parallel to the tissue boundary, (2) in approximately 30% of cortical
      regions, the estimated cluster size of LB, LN, and LG was within the size range
      of cellular columns associated with the cortico-cortical pathways, (3) regularly
      distributed clusters were present in anatomically connected regions, and (4) the
      clustering pattern was similar to that of prion protein (PrPsc) deposits in
      Creutzfeldt-Jacob disease (CJD). The clustering patterns of LB, LN, and LG were
      similar to those exhibited by cellular inclusions in other synucleinopathies and
      by PrPsc deposits in prion disease and therefore, anatomical spread of pathogenic
      ?-synuclein could be involved in the pathogenesis of PDD.</i>.

PMID- 28430290
TI  - Frequency and topography of small cerebrovascular lesions in vascular and in
      mixed dementia: a post-mortem 7-tesla magnetic resonance imaging study with
      neuropathological correlates.
AB  - <i><b>Introduction</b>: Mixed dementia (MixD) refers to a combination of definite
      Alzheimer's disease (AD) and vascular encephalopathy. The existence of a "pure"
      type of vascular dementia (VaD) is controversial. There is a need to find
      magnetic resonance imaging (MRI) characteristics allowing the distinction between
      VaD and MixD. The present post-mortem 7.0-tesla MRI compares the frequency or
      severity and the topography of the small cerebrovascular lesions in brains of
      patients with VaD and with MixD. <b>Material and methods</b>: Based on
      neuropathological criteria, 14 brains were classified as VaD, 24 as MixD and 11
      as controls. Three coronal sections of a cerebral hemisphere and a horizontal
      section of a cerebellar hemisphere underwent T2 and T2* 7.0-tesla MRI
      examination. The mean values and topographic distribution of white matter changes
      (WMCs), lacunar infarcts (LIs), cortical microbleeds (CoMBs) and cortical
      microinfarcts (CoMIs) were determined and compared between the different groups.
      <b>Results</b>: Compared to the controls, both VaD and MixD brains had
      significantly more severe WMCs and increased numbers of CoMBs and CoMIs. Lacunar
      infarcts predominated only in the VaD cases. On mutual comparison of VaD and MixD
      brains, CoMBs and CoMIs predominated in the frontal lobe and the cerebellum of
      VaD, while were mainly present in the occipital lobe of MixD. White matter
      changes predominated in the temporal lobe of MixD cases. Lacunar infarcts were
      significantly increased in the corona radiata and putamen of VaD patients.
      <b>Conclusions</b>: The present post-mortem MRI study shows clear differences in
      the distribution and the types of cerebrovascular lesions on high-field MRI,
      confirming that VaD and MixD are different diseases. </i>.

PMID- 28430291
TI  - Status of the brain antioxidant system at different growing periods after
      prenatal stress and N -acetyl cysteine administration.
AB  - <i>Prenatal stress-induced neurobehavioral deficits observed in offspring are
      multifactorial, including oxidative stress in the developing brain. The time by
      which the developing brain acquires self-defense against oxidative stress is not
      clear. Hence in the present study we aimed to evaluate the brain antioxidant
      status during different developing periods. Further the study also evaluates the
      role of the glutathione precursor, N-acetyl cysteine (NAC) on the brain
      antioxidant status. Pregnant rats were subjected to restraint stress during an
      early or late gestational period. Another set of rats received NAC during the
      entire gestational period along with early or late gestational stress. The study
      parameters included several antioxidant studies directly from rat brain
      homogenate on postnatal day 24 or 48. Early or late gestational stress has caused
      severe oxidative stress in the developing brain on postnatal day 24 in all the
      parameters studied. However, brain reduced glutathione (GSH), superoxide
      dismutase (SOD) and total antioxidant activity (TAO) were not affected by either
      early or late gestational stress on postnatal day 48, but the brain
      malondialdehyde (MDA) level remained high and brain glutathione reductase (GSS
      Rd) level remained low on postnatal day 48. Prenatal NAC treatment has reversed
      the oxidative damage in all the parameters on postnatal day 24 and also the brain
      MDA level and GSS-Rd level on postnatal day 48. This study confirms that the
      growing brain acquires antioxidant capacity over time but during early postnatal
      development it is vulnerable to oxidative stress and related neurological
      consequences. N-acetyl cysteine treatment during the prenatal period as an
      antioxidant supplement exerted a beneficiary effect in this study. Hence
      glutathione supplement in the nutritional source would be an idealistic approach
      to prenatal stress-induced neurological comorbidities in children.</i>.

PMID- 28430292
TI  - Failure of the vascular hypothesis of multiple sclerosis in a rat model of
      chronic cerebrospinal venous insufficiency.
AB  - <i>Chronic cerebrospinal venous insufficiency (CCSVI) is a series of stenotic
      malformations in the cerebrospinal venous outflow routes, which is postulated to
      cause multiple sclerosis (MS). The hypotheses assumed that CCSVI leads to iron
      deposition which triggers inflammation and demyelination in MS. Invasive
      endovascular treatment of CCSVI was initiated based on the previous theory. The
      present study was designed to validate this hypothesis using a rat model of
      CCSVI. Bilateral jugular vein ligation (JVL) was performed on female albino rats
      (n = 15), and sham-operated rats (n = 15) were used as a control group. The rats
      were followed clinically for eight months and neurological examination detected
      no weakness or paralysis in the operated rats. At the end of the experiment, the
      rats were sacrificed and the brains were processed for histopathological
      examination of tissue sections stained by hematoxylin and eosin, myelin stain,
      silver impregnation, iron stain and immunohistochemical preparations for GFAP,
      CD68 and CD45. Semithin sections stained with toluidine blue were also examined.
      In the JVL group, increased iron deposition in the white matter was detected. An
      increase in the size and number of astrocytes along with increased GFAP
      immunoreactivity denoting reactive gliosis was also noted in the JVL group.
      However, no signs of demyelination, inflammation or axonopathy were detected.
      This study revealed that iron deposition in the JVL group as a model for CCSVI
      was not associated with cardinal histopathological findings of MS. It is
      therefore recommended that the invasive endovascular treatment of CCSVI should be
      reconsidered and further controlled clinical studies be carried out to provide a
      better understanding of the pathogeneses of MS.</i>.

PMID- 28430293
TI  - Three cases of ectopic sphenoid sinus pituitary adenoma.
AB  - <i><b>Introduction</b>: Ectopic sphenoid sinus pituitary adenoma is a rare tumour
      originating from embryologic remnants of Rathke's pouch. Although it is
      considered a clinically benign neoplasm, necrosis is encountered in 25% of cases
      and it can invade adjacent bone structures. <b>Aims</b>: To establish clinical,
      radiological and histopathological features of ectopic sphenoid sinus pituitary
      adenoma. <b>Material and methods: </b> Analysis of three cases: two females and
      one man, aged 61-70. <b>Results</b>: One patient presented with a unilateral
      hearing loss, the other two with headache and vertigo. They all suffered from
      type 2 diabetes mellitus. Neurological examination revealed no abnormality.
      Radiological imaging showed a sphenoid sinus space-occupying soft-tissue lesion
      with bone erosion in 2 cases and empty sella in 2 patients whereas one had a
      normal pituitary gland. All were operated on via the transnasal approach. Total
      resection was achieved in one patient and subtotal in two; in two cases we
      observed intact sellar dura and in one intact sellar floor. Histopathology showed
      immunoreactivity for synaptophysin in all cases and cytokeratin in two. The Ki-67
      index was less than 2%. Immunohistochemical staining demonstrated growth hormone
      cells in all cases whereas prolactin and adrenocorticotropin in two. The patients
      were discharged home in good condition with no neurological deficits.
      <b>Conclusions</b>: Ectopic sphenoid sinus pituitary adenoma should always be
      considered in differential diagnosis of sphenoid sinus lesion in the elderly,
      especially in coexistence with empty sella or type 2 diabetes mellitus. Since
      ectopic sphenoid sinus pituitary adenoma is a benign lesion, surgical removal is
      an effective treatment. </i>.

PMID- 28430294
TI  - GRN mutation in a patient with a behavioral variant of frontotemporal lobar
      degeneration (bvFTD).
AB  - <i>The clinical spectrum of frontotemporal lobar degeneration (FTLD) is
      characterized by personality changes, language impairment, and executive function
      deficits. About 40% of FTLD cases have a family history of the disease, and the
      GRN gene is currently the most frequent genetic determinant. In cases of
      inherited FTLD with GRN mutations, parkinsonism is often an early sign due to
      greater grey matter atrophy in the caudate nucleus and bilateral atrophy in the
      thalamus. We investigated a female patient with signs of frontotemporal lobe
      atrophy and unilateral caudate nucleus atrophy on MRI. DNA was isolated from
      peripheral blood leukocytes and tested for GRN gene mutations. A pathogenic
      splice donor site mutation, c.708+1G>A, was found in the GRN gene. MRI showed
      unilateral caudate nucleus atrophy. This report extends the evidence for
      phenotypic and neuropathological heterogeneity in FTLD spectrum disorders due to
      splicing mutations in the GRN gene. </i>.

PMID- 28430295
TI  - Multiple cerebral fusiform aneurysms involving the posterior and anterior
      circulation including the anterior cerebral artery: a case report.
AB  - <i>Multiple fusiform aneurysms occurring in a single patient are very uncommon.
      Fusiform aneurysms affecting the anterior circulation are extremely rare and
      reported cases involve the middle cerebral artery and internal carotid artery. We
      report here a case of a 55-year-old African American male who had a history of
      multiple strokes and who was found unresponsive prior to his latest hospital
      admission. Neuroimaging was remarkable for multiple fusiform aneurysms involving
      segments of the anterior, middle and posterior cerebral arteries as well as
      subarachnoid and intraparenchymal hemorrhage. Unfortunately even after aggressive
      medical management, the patient did not show any signs of recovery and further
      management entailed comfort care measures only. The patient passed away shortly
      thereafter. Post-mortem examination confirmed the presence of multiple fusiform
      aneurysms with involvement of both the posterior and anterior circulation
      including the anterior cerebral artery as well as subarachnoid and
      intraparenchymal hemorrhage. Interestingly, there was no apparent site of
      aneurysm rupture identified to explain the hemorrhage. Our case is unusual in
      that the multiple fusiform aneurysms were found to extensively involve both the
      anterior and posterior circulation. Furthermore, our case demonstrates
      involvement of the anterior cerebral artery by fusiform aneurysms, which is also
      a very rare event. </i>.

PMID- 28430296
TI  - Effect of body mass index on the outcome of surgical patients receiving
      extracorporeal devices (VV ECMO, pECLA) for respiratory failure.
AB  - INTRODUCTION: To determine whether obese surgical patients are at a significant
      disadvantage in terms of outcomes after extracorporeal device (ECD) support, such
      as veno-venous extracorporeal membrane oxygenation (VV ECMO) or pumpless
      extracorporeal lung assist (pECLA), for respiratory failure, the relationship
      between body mass index (BMI) and hospital outcomes was analyzed. METHODS: This
      retrospective study included data on patients who were supported with an ECD
      between January 1, 2008 and December 31, 2014. The analysis included 89 patients
      (74 male). RESULTS: The median BMI was 30 kg/m2 (19-88.5). The median duration of
      the ECD support was 9.0 days, with a maximum of 37.1 days. The median LOS (length
      of stay) in the intensive care unit (ICU) was 21 days (range 0.06-197.6). The
      median hospital LOS was 34.9 days (range 0.1-213.8). VV ECMO was performed 72
      times, and pECLA was performed 18 times. The number of patients successfully
      weaned off the ECD was 54 (60.6%). Survival at the discharge from the hospital
      was 48.3%. CONCLUSIONS: 54 (60.6%) patients were successfully weaned off the ECD;
      43 (48.3%) patients survived and were discharged from the hospital. The analysis
      of correlations between BMI and outcomes of surgical patients treated with ECD
      showed no association between BMI and mortality. Complications (especially
      oxygenator clotting) were not more frequent in obese and extremely obese
      patients. We hypothesized that patients with higher or morbid BMIs would have
      increased mortality after ECD support. A BMI of 30.66 kg/m2 corresponded to the
      desired sensitivity and specificity to predict mortality. This finding applied
      only to the study group. Treatment with ECD in obese patients presents unique
      challenges, including percutaneous cannulation and increased staff requirements.
      However, based on these data, obesity should not be an exclusion criterion for
      ECD therapy.

PMID- 28430297
TI  - Stopping conventional showering decreases Pseudomonas infections in left
      ventricular assist device patients.
AB  - BACKGROUND: Left ventricular assist device (LVAD) exit-site infections represent
      a major challenge in the era of modern LVADs. Infections caused by Pseudomonas
      are particularly difficult to treat due to limited antibiotic susceptibility. We
      hypothesized that keeping the LVAD exit site dry while bathing could result in
      reduced incidence of Pseudomonas infections. METHODS: Starting in April 2013, all
      patients who underwent placement of HeartMate II (HM II) LVAD were instructed not
      to take conventional showers and to keep the exit site dry while bathing. We
      retrospectively reviewed patients who underwent HeartMate II LVAD implantation at
      our institution. Overall and Pseudomonas exit-site infections were compared
      between two groups: Group 1 was implanted with an LVAD prior to intervention
      (4/1/2013) and Group 2 after the intervention. Both groups were subjected to
      cumulative hazard analysis and compared using log-rank test. RESULTS: From
      November 2006 to September 2015, 283 patients underwent HM II LVAD placement at a
      single institution (Group 1, 163 patients; Group 2, 120 patients). Median age was
      59 years (interquartile range [IQR] 50-65), and 57 (20%) were female. Overall,
      driveline infection was noted in 86 (30%) patients. Pseudomonas was the causative
      or coexisting organism in 16 (6%) patients. Median days to infection were 347
      (IQR, 162-568). Driveline infection was identified in 69 (42%) patients in Group
      1 and 17 (14 %) in Group 2. Pseudomonas was an infectious organism in 15 (9%)
      patients of Group 1 and one (1%) patient of Group 2. The incidence of Pseudomonas
      exit-site infections (p = 0.077) decreased substantially after the intervention.
      CONCLUSIONS: Stopping conventional showering may reduce the rate of Pseudomonas
      LVAD exit-site infections. Additional, multi-institutional data are needed to
      further evaluate these findings.

PMID- 28430298
TI  - An experimental-numerical investigation on the effects of macroporous scaffold
      geometry on cell culture parameters.
AB  - INTRODUCTION: Perfused bioreactors have been demonstrated to be effective in the
      delivery of nutrients and in the removal of waste products to and from the
      interior of cell-populated three-dimensional scaffolds. In this paper, a perfused
      bioreactor hosting a macroporous scaffold provided with a channel is used to
      investigate transport phenomena and culture parameters on cell growth. METHODS:
      MG63 human osteosarcoma cells were seeded on macroporous poly(epsilon
      caprolactone) scaffolds provided with a channel. The scaffolds were cultured in a
      perfused bioreactor and in static conditions for 5 days. Cell viability and
      growth were assessed while the concentration of oxygen, glucose and lactate were
      measured. An in silico, multiphysics, numerical model was set up to study the
      fluid dynamics and the mass transport of the nutrients in the perfused bioreactor
      hosting different scaffold geometries. RESULTS: The experimental and numerical
      results indicated that the specific cell metabolic activity in scaffolds cultured
      under perfusion was 30% greater than scaffolds cultured under static conditions.
      In addition, the scaffold provided with a channel enabled the shear stress to be
      controlled, the initial seeding density to be retained, and adequate mass
      transport and waste removal. CONCLUSIONS: We show that the macroporous scaffold
      provided with a channel cultured in a macroscale bioreactor can be a robust
      reference experimental model system to systematically investigate and assess
      crucial culture parameters. We also show that such an experimental model system
      can be employed as a simplified "representative unit" to improve the performance
      of both perfused culture systems and hollow, fiber-integrated scaffolds for large
      scale tissue engineering.

PMID- 28430299
TI  - Effect of retreatment instruments on microcrack formation: a microcomputed
      tomography study.
AB  - INTRODUCTION: The purpose of this study was to compare the occurrence of
      microcracks in teeth prepared with different retreatment systems using
      microcomputed tomography (micro-CT). METHODS: Forty-two freshly extracted
      mandibular premolar teeth were used. The root canals were instrumented with
      stainless steel K-files to an apical size of 35/.02 using the balanced-force
      technique and were obturated using the passive compaction technique. The
      specimens were divided into 3 experimental groups according to retreatment system
      used (n = 14): ProTaper Universal retreatment (PTUR), Mtwo retreatment (MTR), or
      D-RaCe retreatment (D-RC) systems. Each specimen was scanned using a high
      resolution micro-CT system before instrumentation, after obturation, and after
      the removal of the filling material. The images were evaluated, and the presence
      of microcracks was recorded. RESULTS: The PTUR system demonstrated the highest
      percentage, while MTR and D-RC retreatment systems resulted in similar numbers of
      microcracks. CONCLUSIONS: Clinicians should be aware that all retreatment systems
      may cause microcracks.

PMID- 28430300
TI  - Left ventricular assist pump pocket infection: conservative treatment strategy
      for destination therapy candidates.
AB  - BACKGROUND: Heart failure is a major cause of mortality and morbidity,
      particularly among patients with advanced disease and no access to cardiac
      transplantation. LVAD implantation is not only a bridge-to-transplantation option
      for patients awaiting a heart donor, but is often used as bridge-to-destination
      therapy in patients unsuited for transplantation for various reasons. LVAD
      infection is considered the second-most common cause of death in patients who
      survive the initial 6 months on LVAD support. Few reports describe the
      indications for chronic suppressing antibiotic therapy, device exchange, methods
      for exchanging infected devices, post-exchange antimicrobial management status,
      and the outcomes of such patients. CASE PRESENTATION: This is the case of a 74
      year-old male patient with numerous comorbidities who received urgent surgical
      management for severe heart failure with a HeartMate II. Six months later he
      developed an LVAD pump infection with methicillin-resistant Staphylococcus
      epidermidis, which was diagnosed with leucocyte scintigraphy. The patient
      received an omental graft over the LVAD and a chronic suppressive antibiotic
      regime. A marked leukocyte scintigraphy showed the infection's regression 6
      months after the initiation of antibiotic treatment. DISCUSSION: We concisely
      reviewed the driveline infections and the main aspects of the LVAD pump
      infection. We reviewed options for conservative and nonconservative management
      and showed that conservative management of the LVAD pump infection is possible.
      CONCLUSIONS: There are no defined recommendations for the management of LVAD pump
      infection. This case is among the few in the literature showing that conservative
      treatment of an LVAD pump infection is possible.

PMID- 28430301
TI  - Towards a bioengineered kidney: recellularization strategies for decellularized
      native kidney scaffolds.
AB  - Patients with end-stage renal disease often undergo dialysis as a partial
      substitute for kidney function while waiting for their only treatment option: a
      kidney transplant. Several research directions emerged for alternatives in
      support of the ever-growing numbers of patients. Recent years brought big steps
      forward in the field, with researchers questioning and improving the current
      dialysis devices as well as moving towards the design of a bioengineered kidney.
      Whole-organ engineering is also being explored as a possibility, making use of
      animal or human kidney scaffolds for engineering a transplantable organ. While
      this is not a new strategy, having been applied so far for thin tissues, it is a
      novel approach for complex organs such as the kidneys. Kidneys can be
      decellularized and the remaining scaffold consisting of an extracellular matrix
      can be repopulated with (autologous) cells, aiming at growing ex vivo a fully
      transplantable organ. In a broader view, such organs might also be used for a
      better understanding of fundamental biological concepts and disease mechanisms,
      drug screening and toxicological investigations, opening new pathways in the
      treatment of kidney disease.Decellularization of whole organs has been widely
      explored and described; therefore, this manuscript only briefly reviews some
      important considerations with an emphasis on scaffold decontamination, but
      focuses further on recellularization strategies. Critical aspects, including cell
      types and sources that can be used for recellularization, seeding strategies and
      possible applications beyond renal replacement are discussed.

PMID- 28430302
TI  - The Blue Journal after 40 years.

PMID- 28430303
TI  - Echocardiographic outflow pump ramp test in centrifugal-flow left ventricular
      assist device.
AB  - This study sought to develop a novel echocardiogram outflow ramp test to detect
      device malfunctions in centrifugal-flow left ventricular assist devices (LVADs).
      This new ramp pump test is based on the direct analyses of systolic and diastolic
      ratio (S/D) Doppler velocity in the outflow cannula in the HeartWare LVAD during
      progressive increases in speed. The results showed that in patients with normal
      pump function, the Doppler velocity S/D ratio gradually decreased during LVAD
      speed increases. This test is easily performed and seems promising to detect
      normal pump function in patients assisted by a centrifugal flow LVAD.

PMID- 28430304
TI  - Pre-ECMO coagulopathy does not increase the occurrence of hemorrhage during
      extracorporeal support.
AB  - INTRODUCTION AND METHODS: Observational retrospective cohort study to evaluate
      the association between precannulation coagulopathy and the occurrence of
      hemorrhage during extracorporeal membrane oxygenation (ECMO) in neonatal and
      pediatric patients at a tertiary children's hospital. RESULTS: Of 241 patients
      supported with ECMO between January 2009 and December 2014, 175 (72.6%) had
      precannulation coagulation laboratory data and were included in the study. Of the
      eligible patients, 84 (48%) were identified as coagulopathic and 91 (52%) were
      noncoagulopathic. In the coagulopathic group, sepsis (27.3%) was the most common
      diagnosis leading to ECMO. Over half of the patients in both groups (55.9% of the
      coagulopathic and 52.7% of the noncoagulopathic group) developed hemorrhagic
      complications during ECMO support. The most frequent bleeding sites for both
      groups were the cannulation site (24%), the chest tube site (17%), and
      intracranial (10%). Pre-ECMO coagulopathy was not associated with higher
      incidence of hemorrhage during extracorporeal support (p = 0.76). CONCLUSIONS:
      Pre-ECMO coagulopathy was frequent in our cohort but did not increase the
      occurrence of hemorrhage during extracorporeal support. Although the
      identification of factors associated with hemorrhage is key to safely managing
      ECMO anticoagulation, the implication of precannulation coagulopathy seems to be
      minimal.

PMID- 28430305
TI  - Turbulence measurements in an axial rotary blood pump with laser Doppler
      velocimetry.
AB  - BACKGROUND: The implantation of rotary blood pumps as ventricular assist devices
      (VADs) has become a viable therapy for quite a number of patients with end-stage
      heart failure. However, these rotary blood pumps cause adverse events that are
      related to blood trauma. It is currently believed that turbulence in the pump
      flow plays a significant role. But turbulence has not been measured to date
      because there is no optical access to the flow space in rotary blood pumps
      because of their opaque casings. METHODS: This difficulty is overcome with a
      scaled-up model of the HeartMate II (HM II) rotary blood pump with a transparent
      acrylic housing. A 2-component laser Doppler velocimetry (LDV) system was used
      for the measurement of time resolved velocity profiles and velocity spectra
      upstream and downstream of the rotor blades. Observing similarity laws, the speed
      and pump head were adjusted to correspond closely to the design point of the
      original pump - 10,600 rpm speed and 80 mmHg pressure head. A model fluid
      consisting of a water-glycerol mixture was used. RESULTS: The measured velocity
      spectra were scalable by the Kolmogorov length and the Kolmogorov length was
      estimated to be between 14 and 24 um at original scale, thus being about 1.5 to 3
      times the size of a red blood cell. CONCLUSIONS: It can be concluded that
      turbulence is indeed present in the investigated blood pump and that it can be
      described by Kolmogorov's theory of turbulence. The size of the smallest vortices
      compares well to the turbulence length scales as found in prosthetic heart
      valves, for example.

PMID- 28430306
TI  - Endovascular covered stenting to treat an arteriovenous graft to native vein
      fistula, caused by dialysis needle cannulation.

PMID- 28430307
TI  - The incidence and risk factors of coronary steal after ipsilateral AVF in
      patients with a coronary artery bypass graft.
AB  - OBJECTIVE: Ipsilateral arteriovenous fistula (AVF) may cause symptoms of coronary
      steal in patients who had undergone coronary artery bypass graft (CABG) using
      internal thoracic artery. The purpose of this study was to evaluate the adverse
      effects of ipsilateral AVF to CABG, including the incidence of coronary steal,
      and to analyze the risk factors for coronary steal. METHODS: Between 2000 and
      2013, a total of 25 patients undergoing hemodialysis via upper extremity AVF,
      ipsilateral to the preexisting CABG, were reviewed retrospectively. Clinical
      assessment related to coronary steal, echocardiography before AVF, and coronary
      angiography after symptoms were assessed. The definition of coronary steal was
      the new development of one or more of the following symptoms within 12 weeks
      after AVF creation: chest pain, chest discomfort, and dyspnea. RESULTS: Three
      patients were clinically diagnosed as coronary steal. Left ventricular ejection
      fraction (LVEF) was statistically lower in coronary steal group compared to no
      steal group (41.7% vs. 50.9%; p = 0.036). Patients with coronary steal were older
      at the age of CABG surgery and showed a higher incidence of regional wall motion
      abnormality. CONCLUSIONS: Coronary steal after ipsilateral AVF creation in
      patients with CABG using in situ internal thoracic artery (ITA) developed in 12%,
      which can be related to low LVEF. In patients with CABG requiring AVF for
      hemodialysis, the ipsilateral fistula to the grafted ITA should be carefully
      selected and performed.

PMID- 28430308
TI  - Arteriovenous access banding revisited.
AB  - PURPOSE: The aim of this study is to validate the current applicability of
      arteriovenous access banding in high flow access (HFA) and/or haemodialysis
      access-induced distal ischaemia (HAIDI). METHODS: This retrospective study was
      conducted at the GEV (Grupo de Estudos Vasculares) vascular access centre. The
      clinical records of consecutive patients undergoing banding for HAIDI and HFA
      symptoms, between June 2011 and January 2015, were reviewed until April 2015. All
      vascular access patients' consultation records and surgical notes were reviewed.
      We analysed and compared patients' age, gender, comorbidities, symptoms and
      intraoperative ultrasound control. We defined technical failure as recurrence of
      symptoms, requiring new banding. Excessive banding, access thrombosis, rupture
      and false aneurysm development were registered as complications. Primary clinical
      success was defined as improvement of symptoms or effective flow reduction after
      banding, with no need for reintervention. If one reintervention was necessary, we
      have defined it as secondary clinical success. RESULTS: Overall, 119 patients
      underwent banding: 64 (54%) with HAIDI and 55 (46%) with HFA. The HAIDI group was
      significantly older (65 +/- 13 years compared with 56 +/- 22 years, p = 0.001)
      and had significantly greater number of patients with diabetes (56% vs 24%, p =
      0.004). Primary success was achieved in 85 patients (71.4%) and the secondary
      success rate was 84.9%. Older age (p = 0.016) and intraoperative ultrasound
      control (p = 0.012) were significantly associated with primary success.
      CONCLUSIONS: Our results do not corroborate the high incidence of thrombosis
      previously reported as associated with AV access banding and suggest that
      ultrasound control is crucial for preventing technical failure. The procedure was
      effective on both compared groups.

PMID- 28430309
TI  - Variation in use of technology among vascular access specialists: an analysis of
      the PICC1 survey.
AB  - BACKGROUND: While the use of technologies such as ultrasound and
      electrocardiographic (ECG) guidance systems to place peripherally inserted
      central catheters (PICCs) has grown, little is known about the clinicians who use
      these tools or their work settings. METHODS: Using data from a national survey of
      vascular access specialists, we identified technology users as PICC inserters
      that: (a) use ultrasound to find a suitable vein for catheter placement; (b)
      measure catheter-to-vein ratio; and (c) use ECG for PICC placement. Individual
      and organizational-level characteristics between technology users versus non
      users were assessed. Bivariable comparisons were made using Chi-squared or
      Fisher's exact tests; two-sided alpha with p<0.05 was considered statistically
      significant. RESULTS: Of the 2762 PICC inserters who accessed the survey, 1518
      (55%) provided information regarding technology use. Technology users reported
      greater experience than non-technology users, with a higher percentage stating
      they had placed >1000 PICCs (55% vs. 45%, p<0.001). A significantly greater
      percentage of technology users also reported being certified in vascular access
      by an external agency than non-technology users (75% vs. 63%, p<0.001).
      Technology users were more often part of vascular access teams with >=10 members
      compared to non-technology users (35% vs. 22%, p<0.001). Some practices also
      varied between the two groups: for example, use of certain securement devices and
      dressings differed between technology users and non-users (p<0.001). CONCLUSIONS:
      Technology use by vascular access clinicians while placing PICCs is associated
      with clinician characteristics, work setting and practice factors. Understanding
      whether such differences influence clinical care or patient outcomes appears
      necessary.

PMID- 28430310
TI  - Vascular access for hemodialysis and tattoos: a consideration to bear in mind.

PMID- 28430311
TI  - Effect of hemodialysis access blood flow on cardiac events after coronary artery
      bypass grafting using an internal thoracic artery.
AB  - BACKGROUND: The possibility of coronary steal through an arteriovenous fistula
      (AVF) in hemodialysis (HD) patients with coronary artery bypass grafts (CABGs)
      using an ipsilateral internal thoracic artery (ITA) has been suggested. In order
      to define the significance of such a possibility, we analyzed cardiac events and
      mortality risk in patients in relation to AVF flow. METHODS: A retrospective
      cohort study was performed on prevalent HD patients from a single center. The
      outcomes included a first cardiac event, cardiac death and death from any cause.
      RESULTS: The group consisted of 23 chronic HD patients having ITA CABG and upper
      extremity AV access, 12 patients had an ipsilateral and 11 patients had a
      contralateral location of ITA CABG and an upper extremity AV access. The mean
      follow-up period was for 37.0 months.Multivariable Cox proportional-hazards
      regression analysis of risk of death from any cause in relation to AV access flow
      showed no increased risk, neither in the group with ipsilateral location of ITA
      grafts and dialysis accesses (adjusted HR, 3.047 [95% CI, 0.996 to 1.000], p =
      0.081), nor in the group with contralateral location of both shunts (adjusted HR,
      0.173 [95% CI, 0.997 to 1.002], p = 0.678). There was no significant correlation
      between AV access blood flow and the risk of first cardiac event as well as
      cardiac death in either study group. CONCLUSIONS: In this study on HD patients
      having ipsilateral ITA CABG and AVF, fistula flow rate was not found to be
      associated with mortality or cardiac risk.

PMID- 28430312
TI  - Inadvertent cannulation of vertebral artery with a dialysis catheter.

PMID- 28430313
TI  - Successful balloon assisted percutaneous thrombin injection of right subclavian
      artery pseudoaneurysm.
AB  - PURPOSE: To report the use of a balloon catheter to facilitate percutaneous
      ultrasound-guided thrombin injection of a subclavian artery pseudoaneurysm. CASE
      REPORT: A 36-year-old man presented with hoarseness after the insertion of a
      right temporary internal jugular line. Arteriography showed a short neck right
      subclavian artery pseudoaneurysm. A 6 mm * 40 mm balloon catheter was positioned
      across the neck of the pseudoaneurysm to permit percutaneous ultrasound-guided
      thrombin injection. Immediate post-treatment angiogram demonstrated no filling of
      the pseudoaneurysm. Seven-month clinical and imaging follow-up confirmed
      resolution of the pseudoaneurysm and hoarseness. CONCLUSIONS: This clinical
      vignette highlights the potential of balloon catheter-assisted percutaneous
      ultrasound-guided thrombin injection as an alternative to open or endovascular
      repair of pseudoaneurysms of the subclavian arteries.

PMID- 28430314
TI  - Transulnar approach as an alternative to transradial approach in non-coronary
      intervention: safety, feasibility and technical factors.
AB  - PURPOSE: Transulnar access (TUA) has been shown to be an effective alternative to
      transradial access (TRA) for coronary intervention. This study evaluates the
      safety and efficacy of TUA in patients undergoing visceral interventions in the
      setting of contraindication to TRA. MATERIALS AND METHODS: Patients who underwent
      visceral interventions via ulnar approach were included in the study. Outcome
      variables include technical success, access site and bleeding complications.
      RESULTS: From May 2014 to September 2016, TUA was attempted 17 times in 14
      patients (mean age: 60 years; range: 27 to 81 years) for whom TRA was planned for
      visceral intervention, but contraindicated. Contraindication to TRA included
      Barbeau D waveform (n = 3), radial artery diameter <2 mm (n = 8), known radial
      loop (n = 2), high takeoff of the radial artery (n = 2), prior radial artery
      occlusion (RAO) (n = 1), and radiocephalic arteriovenous fistula (n = 1).
      Interventions included selective internal radiation therapy (SIRT) (n = 4), SIRT
      mapping (n = 2), chemoembolization (n = 6), renal embolization (n = 1) and bland
      liver embolization (n = 4). Technical success was achieved in 94.1% (16/17 cases)
      with the single failure attributed to an inability to cannulate the target vessel
      due to vessel tortuosity, requiring ipsilateral femoral crossover. There were no
      major access site or bleeding complications. Minor adverse events include two
      access site hematomas, which were successfully treated with conservative
      management. CONCLUSIONS: TUA for visceral interventions is a safe and effective
      alternative to femoral approach when TRA is contraindicated.

PMID- 28430316
TI  - Patient with a retained fibrin sheath: echocardiography and chest computed
      tomography findings.

PMID- 28430315
TI  - Adding access blood flow surveillance reduces thrombosis and improves
      arteriovenous fistula patency: a randomized controlled trial.
AB  - PURPOSE: Stenosis is the main cause of arteriovenous fistula (AVF) failure. It is
      still unclear whether surveillance based on vascular access blood flow (QA)
      enhances AVF function and longevity. METHODS: We conducted a three-year follow-up
      randomized, controlled, multicenter, open-label trial to compare QA-based
      surveillance and pre-emptive repair of subclinical stenosis with standard
      monitoring/surveillance techniques in prevalent mature AVFs. AVFs were randomized
      to either the control group (surveillance based on classic alarm criteria; n =
      104) or to the QA group (QA measured quarterly using Doppler ultrasound [M
      Turbo(r)] and ultrasound dilution [Transonic(r)] added to classic surveillance; n
      = 103).The criteria for intervention in the QA group were: 25% reduction in QA,
      QA<500 mL/min or significant stenosis with hemodynamic repercussion (peak
      systolic velocity [PSV] more than 400 cm/sc or PSV pre-stenosis/stenosis higher
      than 3). RESULTS: At the end of follow-up we observed a significant reduction in
      the thrombosis rate in the QA group (0.025 thrombosis/patient/year in the QA
      group vs. 0.086 thrombosis/patient/year in the control group [p = 0.007]). There
      was a significant improvement in the thrombosis-free patency rate (HR, 0.30; 95%
      CI, 0.11-0.82; p = 0.011) and in the secondary patency rate in the QA group (HR,
      0.49; 95% CI, 0.26-0.93; p = 0.030), with no differences in the primary patency
      rate between the groups (HR, 0.98; 95% CI, 0.57-1.61; p = 0.935).There was
      greater need for a central venous catheter and more hospitalizations associated
      with vascular access in the control group (p = 0.034/p = 0.029).Total vascular
      access-related costs were higher in the control group (?227.194 vs. ?133.807; p =
      0.029). CONCLUSIONS: QA-based surveillance combining Doppler ultrasound and
      ultrasound dilution reduces the frequency of thrombosis, is cost effective, and
      improves thrombosis free and secondary patency in autologous AVF.

PMID- 28430317
TI  - Treatment of central venous in-stent restenosis with repeat stent deployment in
      hemodialysis patients.
AB  - PURPOSE: To report patency rates for stent deployment for treatment of in-stent
      stenosis of the central veins of the chest in hemodialysis patients. MATERIALS
      AND METHODS: A retrospective analysis was performed on 29 patients who underwent
      35 secondary percutaneous transluminal stent (PTS) deployments for in-stent
      stenosis within the central veins that were refractory to angioplasty and
      ipsilateral to a functioning hemodialysis access (in-stent PTS group). For
      comparison, patency data were acquired for 47 patients who underwent 78
      successful percutaneous transluminal angioplasty (PTA) procedures for in-stent
      stenosis (in-stent PTA group) and 55 patients who underwent 55 stent deployments
      within native central vein stenosis refractory to angioplasty (native vein PTS
      group). RESULTS: The 3-, 6-, and 12-month primary lesion patency for the in-stent
      PTS group was 73%, 57%, and 32%, respectively. The 3-, 6-, and 12-month primary
      patency for the in-stent PTA group was 70%, 38%, and 17% and for the native vein
      PTS group was 78%, 57%, and 26%, which were similar to the in-stent PTS group (p
      = 0.20 and 0.41, respectively). The 3-, 6-, and 12-month secondary access patency
      was 91%, 73%, and 65% for the in-stent PTS group. Sub-analysis of the in-stent
      PTS group revealed no difference in primary (p = 0.93) or secondary patency rates
      (p = 0.27) of bare metal stents (n = 23) compared with stent grafts (n = 12).
      CONCLUSIONS: Stent deployment for central vein in-stent stenosis refractory to
      angioplasty was associated with reasonable patency rates, which were similar to
      in-stent PTA and native vein PTS.

PMID- 28430318
TI  - Teaching medical students ultrasound-guided vascular access - which learning
      method is best?
AB  - INTRODUCTION: Ultrasound is recommended to guide insertion of peripheral
      intravenous vascular cannulae (PIVC) where difficulty is experienced. Ultrasound
      machines are now common-place and junior doctors are often expected to be able to
      use them. The educational standards for this skill are highly varied, ranging
      from no education, to self-guided internet-based education, to formal, face-to
      face traditional education. In an attempt to decide which educational technique
      our institution should introduce, a small pilot trial comparing educational
      techniques was designed. METHODS: Thirty medical students were enrolled and
      allocated to one of three groups. PIVC placing ability was then observed, tested
      and graded on vascular access phantoms. RESULTS: The formal, face-to-face
      traditional education was rated best by the students, and had the highest success
      rate in PIVC placement, the improvement statistically significant compared to no
      education (p = 0.01) and trending towards significance when compared to self
      directed internet-based education (p<0.06). CONCLUSIONS: The group receiving
      traditional face-to-face teaching on ultrasound-guided vascular access, performed
      significantly better than those not receiving education. As the number of
      ultrasound machines in clinical areas increases, it is important that education
      programs to support their safe and appropriate use are developed.

PMID- 28430319
TI  - Evaluation of a Device for Standardized Measurements of Reading Performance in a
      Prepresbyopic Population.
AB  - PURPOSE: Automated measurements of reading performance are required for clinical
      trials involving presbyopia-correcting surgery options. Repeatability of a
      testing device for reading (Salzburg Reading Desk) was evaluated in a
      prepresbyopic population. METHODS: Subjective reading performance of 50 subjects
      divided into 2 age groups (23-30 years and 38-49 years) with distance-corrected
      eyes was investigated with different log-scaled reading charts. At study entry,
      refractive parameters were measured and distance visual acuity assessed. Two
      standardized binocular measurements were performed for each subject (32.24 +/-
      9.87 days apart [mean +/- SD]). The repeatability of the tests was estimated
      using correlation coefficients, Wilcoxon signed-rank test, and Bland-Altman
      method. RESULTS: The test parameters at both maximum reading rate (MRR)
      measurements demonstrate a strong relationship of age group 2 subjects
      (correlation coefficient [r] = 0.74 p = 10-4) and of younger subjects (age group
      1: r = 0.69, p = 10-4). Prepresbyopic subjects of age group 2 showed moderate
      results for near reading distance (r = 0.67, p = 10-4); by contrast, younger
      subjects had poorer results (r = 0.55, p = 10-3). The Wilcoxon signed-rank test
      revealed agreement between measurements and Bland-Altman plots showed a wide data
      spread for MRR and near reading distance in both groups. CONCLUSIONS: The device
      measures repeatedly selected reading performance parameters of near real world
      conditions, such as MRR, in prepresbyopic populations if several factors are
      taken into account. The option to choose preferred distance leads to more
      variance in measuring repeated reading performance. TRIAL REGISTRATION: German
      Clinical Trials Register (DRKS) registration reference number: DRKS00000784.

PMID- 28430320
TI  - Remnant extraction by using an intraocular lens injector with essential flow.
AB  - PURPOSE: To describe a new technique for remnant removal in cases of posterior
      capsular rupture during cataract surgery and Soemmering ring extraction during
      intraocular lens (IOL) removal. METHODS: An IOL injector, inserted into the
      anterior chamber, provides a new exit for residual lens fragments. Passive fluid
      flow, supplied by an anterior chamber maintainer or some ocular viscoelastic
      device (OVD) injection, delivers the residual fragments into a lumen of the
      injector in assistance with a second device such as a phaco-chopper and vitreous
      cutter. RESULTS: Soemmering rings can be removed safely through small incisions
      even when under the iris. Nucleus fragments in anterior chamber can be removed
      safely. Fragments that fall into the vitreous cavity can float up for removal by
      passive flow. CONCLUSIONS: This new technique, remnant extraction through lens
      injector with essential flow, has several practical advantages over existing
      methods including reduced OVD injection and smaller incision size. It may offer
      an alternative to existing methods of remnant removal in cases of posterior
      capsular rupture during cataract surgery and Soemmering ring extraction.

PMID- 28430321
TI  - Comments to: Visual and anatomic outcomes after conversion to aflibercept in
      neovascular age-related macular degeneration: 12-month results.

PMID- 28430322
TI  - Prewound assisted technique for hydrophobic foldable intraocular lens
      implantation.
AB  - PURPOSE: To describe a technique for intraocular lens (IOL) implantation that
      lessens the degree of surgical invasiveness by implanting a tightly rolled IOL
      through a small incision without touching the eye with the cartridge tip.
      METHODS: An IOL was inserted through an incision by first allowing the leading
      haptic to protrude slightly from the cartridge tip. It was then injected through
      the incision without allowing any part of the cartridge to touch the eye during
      IOL implantation. In one eye, the entire circumference of the beveled portion of
      the cartridge tip was inserted into the anterior chamber to implant the IOL,
      whereas in the other eye, the IOL was inserted through the incision by first
      allowing the leading haptic to protrude slightly from the cartridge tip. It was
      then injected through the incision without allowing any part of the cartridge to
      touch the eye during IOL implantation. We analyzed the incision width before and
      after IOL implantation and the degree of surgically induced astigmatism on the
      day after surgery and at 1 and 3 months after surgery. RESULTS: Using our
      technique, both the amount by which the wound was enlarged and the hydration rate
      were significantly lower compared with conventional IOL implantation. Our method
      enables IOL implantation to be carried out through a small incision at a width
      that was only previously possible with forcible insertion. CONCLUSIONS: Our IOL
      implantation technique can be performed using both hands with no need to
      immobilize the eyeball.

PMID- 28430323
TI  - Povidone-iodine 3-minute exposure time is viable in preparation for cataract
      surgery.
AB  - PURPOSE: Povidone-iodine (PI) is widely used to reduce the preoperative
      conjunctival bacterial load. This study aimed to evaluate the employment of PI
      10% in an attempt to sterilize the ocular surface prior to cataract surgery, and
      to show that PI could be left in contact for 3 minutes. The viability of this
      exposure time in clinical practice, associated adverse events, and visual
      outcomes were documented. METHODS: In this prospective cohort study,
      phacoemulsification cataract surgery was performed in 604 patients by a single
      surgeon. Preoperative preparation was undertaken with PI 10%, applied to the
      cornea, conjunctival sac, eyelids, and periorbital skin with sterile cotton
      gauze. Povidone-iodine was then flushed onto the ocular surface. Operating room
      staff timed the precise duration of exposure. After the 3-minute preparation, the
      lids were thoroughly dried with fresh dry gauze. RESULTS: The median PI exposure
      time was 3.17 minutes, with an interquartile range of 0.25. All cases were
      followed up postoperatively at 1 day, 1 week, and 1 month. There were no
      complications attributable to PI. Visual outcomes were satisfactory. CONCLUSIONS:
      Implementation of a preoperative prophylaxis protocol that used PI 10% with a 3
      minute exposure time can be performed in clinical practice. The 3-minute exposure
      time had no adverse sequelae.

PMID- 28430324
TI  - Negative staining of the vitreous with the use of vital dyes.
AB  - PURPOSE: The vitreous cortex, epiretinal membrane (ERM), and inner limiting
      membrane (ILM) are transparent tissues and are thus difficult to visualize.
      Staining these structures can increase the efficiency of a nontraumatic removal.
      METHODS: The surgeon performs a partial core vitrectomy and induces a posterior
      vitreous detachment. The vital dye is then injected into the retrohyaloid space
      in balanced salt solution (BSS). The dyes used are TWIN (Alchimia srl, Padova,
      Italy), MembraneBlue-Dual (DORC International, Zuidland, the Netherlands), and
      Doubledyne (Alfa Intes, Casoria, Italy). The surgeon can complete the vitrectomy
      and gradually aspirate the dye with the probe. Once the vitrectomy is complete,
      the surgeon can perform the peeling of the ERM without the need to reinject the
      vital dye over the macula. RESULTS: The presence of the dye over the macula
      facilitates visualization of the vitreous cortex by blocking the red reflex and
      increasing the contrast power of the coaxial light probe during the vitrectomy.
      This allows a negative coloration of the vitreous because the dye acts by
      increasing the visibility of the surrounding BSS and not the vitreous itself.
      CONCLUSIONS: We describe a new chromovitrectomy technique using the same dye to
      increase the visualization of the vitreous, posterior hyaloid, ERM, and ILM.

PMID- 28430325
TI  - Identification of a Disease-Causing Mutation in a Chinese Patient with Retinitis
      Pigmentosa by Targeted Next-Generation Sequencing.
AB  - PURPOSE: To identify disease-causing mutations in a Chinese patient with
      retinitis pigmentosa (RP). METHODS: A detailed clinical examination was performed
      on the proband. Targeted next-generation sequencing (NGS) combined with
      bioinformatics analysis was performed on the proband to detect candidate disease
      causing mutations. Sanger sequencing was performed on all subjects to confirm the
      candidate mutations and assess cosegregation within the family. RESULTS: Clinical
      examinations of the proband showed typical characteristics of RP. Three candidate
      heterozygous mutations in 3 genes associated with RP were detected in the proband
      by targeted NGS. The 3 mutations were confirmed by Sanger sequencing and the
      deletion (c.357_358delAA) in PRPF31 was shown to cosegregate with RP phenotype in
      7 affected family members, but not in 3 unaffected family members. CONCLUSIONS:
      The deletion (c.357_358delAA) in PRPF31 was the disease-causing mutation for the
      proband and his affected family members with RP. To our knowledge, this is the
      second report of the deletion and the first report of the other 2 mutations in
      the Chinese population. Targeted NGS combined with bioinformatics analysis proved
      to be an effective molecular diagnostic tool for RP.

PMID- 28430326
TI  - In vivo intraocular pressure monitoring during microincision vitrectomy with and
      without active control of infusion pressure.
AB  - PURPOSE: To evaluate intraocular pressure (IOP) fluctuation during vitrectomy, we
      directly monitored IOP in vivo using 2 vitrectomy machines with or without
      constant infusion pressure monitoring and control. METHODS: Among 61 eyes of 61
      consecutive patients, 32 were assigned to the Accurus system (group 1) and 29
      were assigned to the Constellation system (group 2) in this prospective case
      series. The IOP fluctuations were evaluated during routine vitrectomy procedures.
      RESULTS: The initial IOP before vitrectomy was 20.3 +/- 2.4 mm Hg in group 1
      using a conventional vented gas forced infusion system and 20.0 +/- 0.0 mm Hg in
      group 2 using active IOP control at 20 mm Hg (p = 0.532). However, the average
      IOP change during core vitrectomy was -8.6 +/- 4.3 mm Hg in group 1 and -0.8 +/-
      1.1 in group 2 (p<00.001). Maximum IOP was significantly decreased in group 1 (
      17.0 +/- 2.6 mm Hg) compared with that in group 2 (-4.1 +/- 2.2 mm Hg)
      (p<00.001). Partial ocular collapse was observed during vitrectomy only in group
      1 (78.1%). Peak IOP significantly increased during scleral compression and gas
      and fluid injection but was not significantly different between the groups (all
      p>=0.147). The IOP fluctuation range was 50-70 mm Hg in both groups. CONCLUSIONS:
      The IOP fluctuated significantly during routine vitrectomy using both systems.
      Hypotony and partial ocular collapse were more frequently observed during
      vitrectomy with the Accurus system than with the Constellation system. Both
      systems were vulnerable to IOP surge during indentation and intravitreal
      injection.

PMID- 28430327
TI  - Postoperative Esotropia: Initial Overcorrection or Consecutive Esotropia?
AB  - PURPOSE: To investigate the length of time required for diagnosing consecutive
      esotropia rather than initial overcorrection and examine risk factors for
      persistent postoperative esotropia after intermittent exotropia surgery. METHODS:
      This is a retrospective case series in a tertiary medical center. Fifty
      consecutive patients with postoperative esotropia >=6 prism diopters at 1 week
      following exotropia surgery, managed with nonsurgical management and followed up
      for more than 6 months from 2014 to 2015, were included. Patients were allocated
      to 1 of 2 groups depending on whether the postoperative esotropia was resolved at
      1 month after surgery. Patients with ongoing nonsurgical management were
      reevaluated monthly. Timing that significant resolution occurred was assessed.
      Clinical characteristics and motor and sensory successes were evaluated at 6
      months after surgery. RESULTS: Thirty-two patients were allocated to group 1 and
      18 to group 2. Significant resolution occurred between 1 week and 1 month after
      surgery. Patients were older and preoperative deviation at distance was larger in
      group 2 than in group 1 (p = 0.006 and 0.015). A significantly larger proportion
      of patients in group 2 showed combined vertical deviation (p = 0.019). Motor and
      sensory success rates were comparable. CONCLUSIONS: When initial postoperative
      esotropia persists for more than 1 month, it should be regarded as consecutive
      esotropia. Older age, a larger preoperative deviation, and concurrent vertical
      deviation are risk factors for persistent postoperative esodeviations. Therefore,
      more postoperative attention should be given to these patients.

PMID- 28430328
TI  - Outcome of various Hydrophobic Acrylic Intraocular Lens Implantations in Children
      with Congenital Cataract.
AB  - PURPOSE: To evaluate performance of different intraocular lenses (IOLs) after
      cataract surgery in children aged less than 2 years with regards to rates of
      visual axis opacification (VAO). METHODS: This was a retrospective chart review
      of children <2 years of age undergoing cataract surgery with primary posterior
      capsulotomy, anterior vitrectomy, and IOL over a period of 5 years with minimum
      follow-up of 1 year at a tertiary care institute. Children with microphthalmos,
      persistent fetal vasculature, traumatic cataract, aphakia, secondary IOLs, or any
      other coexisting ocular disease were excluded. RESULTS: A total of 257 eyes of
      159 children were included in the study. The mean age at the time of surgery was
      11.63 +/- 7.916 months (range 6-23 months). A total of 29 eyes of 16 children
      underwent phacoaspiration with implantation of SA60 AT (AcrySof, Alcon, Fort
      Worth, TX); 75 eyes of 45 children received Hoya IOL (Hoya-PS AF-1 Series, Model
      PC-60AD, Hoya, Japan), 70 eyes of 46 patients received Sensar (Abbott Medical
      Optics Inc., Santa Ana, CA, USA), and 83 eyes of 52 children received MA60AC
      (AcrySof). At mean follow-up of 18.31 +/- 15.04 months, 22.46% of the patients
      required resurgery for visual axis obscuration. By multiple regression analysis,
      the rate of visual axis obscuration was affected by the rate of perioperative
      complications (p = 0.001) and not affected by age (p = 0.98), type of IOL (p =
      0.104), or site of IOL implantation (p = 0.603). CONCLUSION: Our findings suggest
      comparable rates of VAO for children less than 2 years of age receiving different
      types of hydrophobic acrylic IOLs.

PMID- 28430329
TI  - Ahmed Valves vs Trabeculectomy Combined with Pans Plana Vitrectomy for
      Neovascular Glaucoma with Vitreous Hemorrhage.
AB  - PURPOSE: Vitreous hemorrhage is common in advanced neovascular glaucoma (NVG),
      which has poor visual prognosis. This study aimed to compare the efficacy of 23-G
      pars planar vitrectomy (PPV) combined with either Ahmed glaucoma valve (AGV)
      implantation or trabeculectomy after intravitreal ranibizumab (IVR) treatment for
      NVG with vitreous hemorrhage. METHODS: This retrospective, nonrandomized study
      included 33 eyes of 33 patients with NVG with vitreous hemorrhage. After IVR
      treatment for 3-7 days, 18 eyes underwent PPV + AGV (AGV group) and 15 underwent
      PPV + trabeculectomy (trabeculectomy group). The success criterion was a
      postoperative intraocular pressure (IOP) of 6-21 mm Hg, with or without
      antiglaucoma medication. RESULTS: Postoperative IOP decreased significantly in
      both groups, but the mean IOP after 12 months was significantly lower in the AGV
      group (16.92 +/- 2.75 mm Hg) than the trabeculectomy group (21.50 +/- 5.79 mm Hg;
      p = 0.018). The AGV group required fewer glaucoma medications than the
      trabeculectomy group. The cumulative probabilities of surgical success rates for
      the AGV and trabeculectomy groups at 12 months were 71.3% and 46.7%,
      respectively. No significant differences in postoperative complications were
      observed between the groups. CONCLUSIONS: For NVG with vitreous hemorrhage, PPV
      with AGV implantation may reduce IOP more effectively than PPV with
      trabeculectomy.

PMID- 28430330
TI  - Long-Term Visual Outcomes in Children with Primary Congenital Glaucoma.
AB  - PURPOSE: To determine the long-term visual outcomes and risk factors for visual
      loss in children with primary congenital glaucoma (PCG) who underwent angle
      surgery over a 21-year period. METHODS: This was a retrospective study of
      patients who underwent trabeculotomy, trabeculectomy, or combined trabeculotomy
      trabeculectomy for PCG. Visual acuity (VA), surgeries, and underlying cause of
      visual impairment were recorded and compared. Main outcome measures were final
      best-corrected good VA (20/20 to 20/50), moderate VA (<20/50 to 20/200), or poor
      VA (<20/200); age at surgery, sex, laterality, type of initial glaucoma surgery,
      and number of surgeries were recorded. RESULTS: Fifty-three eyes were eligible to
      be included in the study. The mean logMAR VA was 0.61 +/- 0.57. A good VA was
      attained in 51%, moderate VA in 30%, and poor VA in 19%. The main cause of visual
      impairment with VA <20/50 was deprivation amblyopia (64%). There was no
      association between VA level and status of success (controlled with or without
      medications) (p = 0.202). The mean spherical equivalent of refraction was -4.47
      +/- 5.66; myopia was the predominant refractive error (74%) and astigmatism >2 D
      (40%). A statistically significant high myopic shift was more frequent in the
      visually impaired group. None of the studied factors was statistically associated
      with moderate to poor visual outcome (all p>0.05). CONCLUSIONS: A favorable VA
      outcome was achieved. Topical antiglaucoma medication has an adjuvant role in
      maintaining the success rate of surgery without risking the visual outcome.
      Corneal opacification and anisometropia were the cause of amblyopia.

PMID- 28430331
TI  - Factors Influencing Intravitreal Bevacizumab and Triamcinolone Treatment in
      Patients with Diabetic Macular Edema.
AB  - PURPOSE: To evaluate factors associated with response to intravitreal bevacizumab
      (IVB) and intravitreal triamcinolone acetonide (IVTA) in diabetic macular edema
      (DME). METHODS: Ninety-one eyes of 88 patients diagnosed with DME were enrolled
      in this retrospective chart review. Group 1 included eyes that showed good
      response to IVB. Group 2 included eyes that did not respond to IVB but responded
      to IVTA. Group 3 included eyes that responded to neither. Clinical factors,
      HbA1c, and optical coherence tomography (OCT) findings including patterns of
      macular edema were compared among the 3 groups. RESULTS: A total of 44, 27, and
      20 eyes were included in groups 1, 2, and 3, respectively. HbA1c was higher in
      group 3 than in the other groups. Proportion of full (combination of all
      patterns) type edema was higher in group 3 than in the other 2 groups. In group
      1, the proportion of sponge-like diffuse retinal thickening type was higher and
      cystoid macular edema type was lower than in the other groups. CONCLUSIONS: The
      degree of diabetic control and morphologic subtypes with OCT should be considered
      to better predict the prognosis after treatment in DME.

PMID- 28430332
TI  - Relationship between corneal biomechanical properties and optic nerve head
      changes after deep sclerectomy.
AB  - PURPOSE: To evaluate corneal biomechanical properties and optic nerve head (ONH)
      changes following deep sclerectomy (DS) and the relation to each other. METHODS:
      Forty-nine eyes with primary open-angle glaucoma that underwent DS were studied.
      Corneal biomechanical properties were assessed using the Ocular Response Analyzer
      and the ONH was evaluated by Spectralis optical coherence tomography with
      enhanced depth imaging technology before surgery and 3 months postoperatively.
      Changes in corneal hysteresis (CH), corneal resistance factor (CRF), optic nerve
      cupping, prelaminar tissue thickness, and lamina cribrosa depth and thickness
      were registered. A correlation matrix and multiple linear regression models were
      used to determine predictors of ONH changes. RESULTS: At 3 months after surgery,
      mean corneal compensated intraocular pressure (IOPcc) significantly decreased by
      27.9% (p<00.001) and mean Goldmann-correlated IOP (IOPg) decreased by 30.52%
      (p<00.001). Mean CH increased and CRF decreased by 18.4% and 10.1%, respectively
      (p<00.001). There was a significant reversal of ONH cupping mainly due to a
      prelaminar tissue thickening (p<00.001). Significant associations were found
      between ONH cupping reversal and prelaminar tissue thickening with preoperative
      IOPcc (p = 0.046), IOPg (p = 0.02), and CRF (p = 0.002) and with changes in IOP,
      CH, and CRF (p<00.001, p = 0.004, p = 0.018, respectively) after surgery.
      CONCLUSIONS: Corneal hysteresis increased and CRF decreased significantly 3
      months after DS. Corneal resistance factor was the single largest preoperative
      factor influencing cupping reversal changes. Despite the influence of
      preoperative variables, postoperative IOP reduction was the only independent
      factor influencing changes observed in the ONH after surgery.

PMID- 28430333
TI  - Epiretinal membrane negative staining and double peeling in a single block with
      Brilliant Blue G.
AB  - PURPOSE: To describe a surgical technique for combined peeling of epiretinal and
      internal limiting membranes. METHODS: The authors present their procedure of
      choice for epiretinal membrane surgery: negative staining effect using Brilliant
      Blue G and single block removal of the epiretinal and internal limiting membranes
      in a single step. RESULTS: A total of 26 eyes were operated with the described
      technique. In all cases, the peeling was performed successfully and with no
      complications. Minimum postoperative follow-up was 12 months. There were no
      recurrences of epiretinal membranes. CONCLUSIONS: The ideal surgical approach for
      epiretinal membranes should attempt to reduce mechanical trauma, light exposure,
      and dye toxicity.

PMID- 28430334
TI  - Chondro-keratoprosthesis: an alternative to OOKP?
AB  - PURPOSE: To evaluate the use of cartilage as a potential graft material toward
      osteo-odontal tissue replacement in keratoprosthesis surgery. METHODS: We
      describe a modification of the osteo-odonto-keratoprosthesis surgery that
      involves the use of autologous auricular conchal cartilage graft (ACCG). In stage
      1a, a full-thickness cheek mucosa graft was performed over the ocular surface. In
      stage 1b, ACCG was harvested via a retroauricular approach. An optical polymethyl
      methacrylate cylinder was embedded into a double-layered fragment of cartilage
      and secured by cyanoacrylate glue. The graft is then placed in a infraorbital
      pocket. Stage 2, performed after 3 months, involved retrieval of the complex and
      implantation after reflection of the mucosal flap, corneal trephination, iris and
      lens removal and anterior vitrectomy. RESULTS: We report two cases of chondro
      keratoprosthesis (CKPRO) who underwent surgery with up to 15 months of follow-up.
      Preoperatively, vision was limited to light perception (LP) in both cases. On
      patient 1, CKPRO was performed in the right eye and the postoperative visual
      acuity stay limited to LP related to preoperative retinal lesions. On patient 2,
      CKPRO was performed in the left eye and the vision was improved to 20/100 J6. No
      postoperative complications such as extrusion, epithelial downgrowth,
      retrocorneal membrane or endophtalmia were observed. CONCLUSIONS: ACCG could be
      an interesting alternative to replace osteo-odontal graft in keratoprosthesis
      surgery. However, further comprehensive studies with larger sample size and
      longer follow-up are required. However longer follow-up and a higher number of
      patient are required to report postoperative complications incidence, survival
      and functional outcomes.

PMID- 28430335
TI  - Reading Ability and Quality of Life in Stargardt Disease.
AB  - PURPOSE: To study the reading performance of patients with Stargardt disease
      (STGD) and the relationship between clinical vision measurements and vision
      related quality of life (VRQOL). METHODS: We studied both eyes of 16 patients
      with STGD. Each patient was examined for best-corrected visual acuity (Early
      Treatment Diabetic Retinopathy Study [ETDRS]), reading ability (MNREAD and REX
      charts), contrast sensitivity (Pelli-Robson charts), fixation study (MP1
      microperimeter), and VRQOL (25-item National Eye Institute Visual Function
      Questionnaire [NEI VFQ-25]). The correlation pattern among these variables was
      examined and an exploratory factor analysis was used to investigate
      dimensionality of both visual function and VRQOL. RESULTS: Mean ETDRS visual
      acuity was about 20/160 (0.9 logMAR). All studied psychophysical measures were
      highly or moderately correlated with MNREAD reading speed (p<0.05 level). A
      similar correlation was found between psychophysical measures and VRQOL, which
      was higher for MNREAD measures of acuity (r = -0.75) and speed (r = 0.74).
      Accordingly, exploratory factor analysis suggested that a single latent dimension
      explained most of the variance of vision psychophysical measures as well as of
      VRQOL. CONCLUSIONS: We propose that reading ability should be assessed in
      patients with STGD, since we found that both MNREAD reading speed and visual
      acuity are strong determinants of quality of life. The observed relation between
      reading ability and VRQOL in STGD suggests that in these patients appropriate low
      vision rehabilitation can improve both reading performance and consequently
      VRQOL. Finally, our data support the use of reading speed and visual acuity as
      important outcome measures for monitoring STGD progression.

PMID- 28430336
TI  - An Italian Translation and Validation of the near Activity Visual Questionnaire
      (NAVQ).
AB  - PURPOSE: To validate the Near Activity Vision Questionnaire (NAVQ) in Italian to
      allow the assessment of presbyopia corrections in Italian-speaking patients.
      METHODS: An Italian version of the NAVQ was arranged through several steps: an
      initial forward translation (from English to Italian), a backward translation
      (from Italian to English), and finally a consensual version to check against the
      original NAVQ. This prospective study enrolled native Italian-speaking presbyopic
      patients with corrected distance visual acuity of 0.20 logMAR or better in each
      eye and free of ocular anomalies. Six different groups of patients were asked to
      complete the questionnaire: emerging presbyopic patients, reading spectacle
      users, multifocal spectacle users, multifocal contact lens (CL) wearers,
      monovision CL wearers, and monofocal intraocular lens patients. Subjects were
      asked to answer the questionnaire again 2 weeks after the first completion.
      RESULTS: A total of 207 subjects completed the questionnaire. Data analysis
      showed good internal consistency (Cronbach alpha = 0.93) and factorial validity
      with only one factor explaining 62.0% of the variance. Test-retest reliability
      was extremely good (ICC = 0.92) as well as discriminatory power of the
      questionnaire's ability to discriminate between subjects with different forms of
      presbyopic correction. CONCLUSIONS: The Italian version of the NAVQ matches the
      properties of the original English version. It is a valid instrument to evaluate
      near activity visual quality of presbyopic Italian speakers.

PMID- 28430337
TI  - Circulating neuregulin-1 and galectin-3 can be prognostic markers in breast
      cancer.
AB  - BACKGROUND: It is important to identify novel plasmatic biomarkers that can
      contribute to assessing the prognosis and outcome of breast cancer patients.
      Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in
      breast cancer development and patient survival; therefore, we studied whether the
      serum concentration of these 2 proteins can be correlated to breast cancer
      progression. METHODS: Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy
      controls and 50 breast cancer patients at baseline and at 3 and 6 months after
      treatment with anthracyclines and taxanes, with or without trastuzumab. RESULTS:
      NRG1 and Gal-3 were significantly more elevated in cancer patients than in
      healthy controls; furthermore, NRG1 and Gal-3 were significantly increased after
      chemotherapy and were predictive of mortality at 1 year. CONCLUSIONS: Circulating
      NRG1 and Gal-3 can be additional biomarkers indicative of prognosis and outcomes
      for breast cancer patients.

PMID- 28430338
TI  - YAP, TAZ and AREG expression in eighth cranial nerve schwannoma.
AB  - BACKGROUND: Although the diagnosis and treatment of eighth cranial nerve (VIII
      CN) schwannoma (acoustic neuroma) has improved over the years, no factors capable
      of predicting tumor growth have been identified as yet. This study is a
      preliminary investigation of the expression in sporadic VIII CN schwannomas of
      Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif
      (TAZ), and amphiregulin (AREG), a direct target gene of YAP and TAZ. The
      expression of YAP, TAZ and AREG was correlated with the volumetric dimensions of
      tumors on contrast-enhanced magnetic resonance imaging (ceMRI). METHODS: YAP, TAZ
      and AREG expression was assessed immunohistochemically in surgical specimens of
      36 consecutive sporadic VIII CN schwannomas. 3D reconstructions of the tumors and
      their corresponding volumes in cm3 were obtained from measurements on ceMRI
      images using the OsiriX(r) software. RESULTS: We found a significant direct
      correlation between TAZ expression and VIII CN schwannoma volumes on latest
      preoperative ceMRI (p<0.0003). Mean TAZ expression was also significantly higher
      in VIII CN schwannomas with a volume >=2.1 cm3 than in those with a volume <2.1
      cm3(p<0.0018). No significant correlations emerged for YAP or AREG expression and
      VIII CN schwannoma volume. CONCLUSIONS: The immunohistochemical expression of TAZ
      (but not YAP or AREG) correlated significantly with schwannoma volume measured on
      ceMRI. Further investigations are needed to identify the biological factors
      influencing tumor proliferation (ideally secreted proteins like AREG) that might
      be detected using non-invasive approaches (i.e., blood samples).

PMID- 28430339
TI  - Characterization of a rare nonpathogenic sequence variant (c.1905C>T) of the
      dihydropyrimidine dehydrogenase gene (DPYD).
AB  - BACKGROUND: In the era of precision medicine, the suitability of fluoropyrimidine
      therapies in clinical oncology can be checked by pharmacogenetic investigations
      of single patients, thus optimizing resources and indicating the appropriate
      drugs to personalize their chemotherapy. For example, the presence of
      dihydropyrimidine dehydrogenase gene (DPYD) polymorphisms in cancer patients may
      lead to adverse effects when adopting fluoropyrimidine-based therapies. METHODS:
      We detected in a cancer patient a rare germline synonymous heterozygous variant
      of DPYD (c.1905C>T) in proximity to the exon 14 splice donor site. Because in
      silico analyses hypothesized potential deleterious effects of the splice site, we
      performed both quantitative and qualitative mRNA analyses to investigate the
      possible pathogenic nature of the variant. RESULTS: We did not detect any
      alterations in mRNA expression or in the cDNA sequence of DPYD gene transcript.
      CONCLUSIONS: Our observations suggest that the c.1905C>T variant of DPYD does not
      have a pathogenic effect. Therefore, assessment of the clinical significance of
      rare sequence variants could emphasize the predictive value of DPYD gene
      alterations in identifying patients at potential risk for fluoropyrimidine
      related toxicity.

PMID- 28430340
TI  - Transurethral contact ureterolithotripsy in gas (SO2) medium.
AB  - BACKGROUND: Transurethral intracorporeal lithotripsy is the modality of choice
      for the endoscopic disintegration of large, long-standing, radiolucent or high
      density stones. Despite several advantages and proven benefits of contact
      ureterolithotripsy/ureterolithoextraction (CULT), the application of irrigation
      carries significant risks of untoward perioperative events including retrograde
      stone migration and postoperative pyelonephritis. METHODS: We describe a new
      technique - endoscopic intracorporeal lithotripsy in the gas (SO2) medium. It is
      a prospective randomized, single blinded pilot study that included total of (n =
      60) patients with urolithiasis who were allocated to either experimental or
      control group. Out of the total pool of patients, 30 underwent treatment with the
      new approach (experimental group) and other 30 (control group) had contact
      ureterolithotripsy in a standard of care 0.9% NaCL medium. We included patients
      >18 years old, with known symptomatic renal calculi disease who were eligible and
      scheduled for CULT and free from significant coexisting pathologies of urinary
      tract. RESULTS: No retrograde migration of the stone fragments into the kidney
      was reported in the experimental group [complications rate 0%, confidence
      interval (CI): 0-11.6%]. In the control group, complications were observed in
      eight cases (complications rate 26.7%, CI: 14.7-42.3%); retrograde migration was
      in five patients (16.6%), and acute pyelonephritis/exacerbation of chronic
      pyelonephritis was seen in three (10%) patients. There was not any acute
      pyelonephritis in the experimental group. Reliability of frequency differences -
      p = 0.0023 (chi2). CONCLUSIONS: The novel method of contact ureterolithotripsy is
      a safe and promising alternative to the conventional contact ureterolithotripsy
      in a fluid medium in a carefully selected patient population.

PMID- 28430341
TI  - Prostate-specific antigen increase during dutasteride to indicate the need for
      prostate biopsy: influence of prostatic inflammation.
AB  - INTRODUCTION: The aim of this study was to analyze the significance of an
      increase in total prostate-specific antigen (PSA) serum levels despite
      dutasteride treatment as a predictor of prostate cancer (PC) at biopsy. We
      focused our attention on the rate of the first PSA increase and on the influence
      of prostatic inflammation. METHODS: From 2011 to 2016, 365 men with a previous
      negative prostate biopsy and persistent elevated PSA levels received dutasteride
      treatment. The population was followed for a range of 12-48 months. RESULTS: One
      hundred twelve cases with a confirmed PSA increase >0.5 ng/ml over the nadir
      value during the follow-up were included in Group A and underwent a new prostate
      biopsy. In Group A, the PSA increase was associated with PC at the re-biopsy in
      66% of cases. The percentage of PSA reduction after 6 months of treatment was not
      a significant indicator of the risk for PC. The distribution of inflammatory
      infiltrates significantly (p<00.01) varied from positive to negative prostate
      biopsies. The relative risk for PC at biopsy significantly increased according to
      PSA level during dutasteride. CONCLUSIONS: Treatment with dutasteride can help to
      analyze PSA kinetic. A persistent prostatic inflammation is a factor able to
      reduce the performance of PSA kinetic during dutasteride treatment.

PMID- 28430342
TI  - Safety and efficacy outcomes of ZSI 475 penile prosthesis.
AB  - OBJECTIVE: The aim of this study was to demonstrate safety and efficacy of ZSI
      475 hydraulic penile prosthesis three components. Preparation, procedure and
      functional results are similar to AMS 700 and Coloplast Titan. This study was
      conducted from September 2012 to December 2016. PATIENTS AND METHOD: From
      September 2012 to December 2016, 29 ZSI 475 hydraulic penile prostheses three
      components were implanted by six surgeons in 28 patients in five European
      centres. Mean age of patients was 60 years old (44-75). Standard peno-scrotal
      incision procedure was performed for the 28 patients. Erectile function was
      assessed by IIEF-5 self-administered questionnaire. RESULTS: Median follow-up was
      35.11 months (8-47). Postoperative complications were limited to scrotal pump
      torsion that required a revision, an armed tubing breakage and a scrotal
      haematoma. At the end of follow-up, 100% of patients had a functional prosthesis
      and 92.86% were satisfied. CONCLUSIONS: Implantation, risks of complications,
      functional outcome and patient satisfaction with penile implant ZSI 475 are
      similar to standard hydraulic penile implants three components as AMS 700 and
      Coloplast Titan.

PMID- 28430343
TI  - Fabrication and characterization of indium tin oxide films.
AB  - BACKGROUND: Transparent conducting oxide (TCO) films are of particular interest
      in the field of optoelectronics, due to the requirement for transparent
      electrodes in applications such as organic light-emitting diodes, solar cells and
      so on. The aim of this study was to obtain a better understanding of the effects
      of preparation temperature on indium tin oxide (ITO) films, to improve their
      performance for optoelectronic applications. METHODS: ITO films were deposited on
      glass substrate at different temperatures, using direct current (DC) magnetron
      sputtering. The influence of substrate temperature on the microstructure and
      electrical and optical properties was studied. The surface topography and
      microstructure of the films were analyzed by atomic force microscopy. The
      electrical resistivity and optical transmittance of the films were measured using
      the Hall effect measurement and spectrometer, respectively. RESULTS: The results
      showed that both the surface roughness and film thickness increased as the
      substrate temperature increased. Transmittance increased from 78% to 80% in the
      visible wavelength region, while resistivity decreased from 6.05 * 10-4 to 3.27 *
      10-4 Omega-cm as the substrate temperature increased from 25 degrees C to 275
      degrees C. CONCLUSIONS: High-quality ITO films with low resistivity and high
      transmittance can be achieved by increasing the deposition temperature.

PMID- 28430344
TI  - Surfactant-assisted synthesis of polyvinylpyrrolidone-hydroxyapatite composites
      as a bone filler.
AB  - BACKGROUND: Different methods have been used to prepare bone-like composites from
      inorganic nanoparticles embedded in polymeric matrixes to obtain the properties
      and structures required for bone fillers. METHODS: Bone-like nano-hydroxyapatite
      (nHA) was synthesized using a biomimetic method, with polyvinylpyrrolidone (PVP)
      as template and sodium dodecyl sulfate (SDS) as surfactant. RESULTS: The results
      demonstrated the formation of HA composites and showed that polymer and
      surfactant as the polymer capsule can be properly used to control the size,
      shape, morphology and dispersion of HA crystals. All of the samples were
      bioactive due to their ability to form carbonate apatite and grow HA on their
      surface. The MTT assay showed that the samples were biocompatible. CONCLUSIONS:
      Based on bioactivity and biocompatibility evaluations, the prepared composites
      can be considered as good candidates for bone filler applications.

PMID- 28430345
TI  - Healing response of rat pulp treated with an injectable keratin hydrogel.
AB  - BACKGROUND: Keratin has shown promising outcomes as a biomaterial due to its
      inherent bioactivity, biocompatibility and regenerative effects. The effect of
      keratin on repair and regeneration of dental tissues has never been studied
      before. Current therapies to treat pulp tissues involve its replacement with
      inert, synthetic materials that do not have a proper biological function, leading
      to failure and tooth loss. This study aimed to develop a biocompatible keratin
      hydrogel (KH) suitable for pulp therapies. METHODS: Keratins extracted from sheep
      wool were isolated, quantified and reconstituted to form KH. Different
      concentrations of keratin gel suitable for dental application were characterized
      by rheological analysis. The optimized gel based on flow characteristics was
      studied further for microstructure including porosity, percentage swelling ratio
      and contact angle measurements, using analytical tools such as scanning electron
      microscopy (SEM), micro-computed tomography and goniometer. To assess both
      biocompatibility and pulpal response, KH was implanted into rat upper molar teeth
      following partial pulpotomy. After 28 days, the tissue sections were analyzed by
      histological and immunohistochemical methods to identify dentin matrix protein 1
      (DMP-1) formation and compared with control (Ca(OH)2-treated) teeth. RESULTS: The
      results of the study demonstrated a viscous and injectable, porous, dimensionally
      stable, hydrophilic and biocompatible gel that allowed pulp healing to occur by a
      reparative response, with widespread DMP-1 expression. CONCLUSIONS: The findings
      of this study indicate that keratins can be developed as a biomaterial source for
      alternate biological treatment options for pulp therapies.

PMID- 28430346
TI  - Facile synthesis of reduced graphene oxide/Fe3O4 nanocomposite film.
AB  - BACKGROUND: This study aims at proposing a facile method to prepare rGO/Fe3O4
      composite film with adjusted magnetic properties and electronic conductivity.
      METHODS: Colloidal solution of graphene oxide (GO)/Fe3O4 nanoparticles (F-NPs)
      with a size in the range of 20-80 nm were prepared by a solution-blending method
      and heated step-by-step from room temperature to 60 degrees C, 120 degrees C and
      160 degrees C for 12 hours, respectively, to obtain a reduced graphene oxide
      (rGO)/F-NP composite film. The structure, morphology, components, magnetic
      properties and electrical conductivity of the composite films were characterized
      by X-ray diffraction, scanning electron microscopy, Fourier transform infrared
      spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy,
      superconducting quantum interference devices and 4-probe instrument. RESULTS: The
      results indicated that the F-NPs were uniformly distributed on the graphene film,
      and the composite exhibited good ferromagnetic properties and conductivity, which
      could be adjusted easily via different loadings of F-NPs. A high content of F-NPs
      (200 mg) led to a strong saturation magnetization of 63.6 emu.g-1, with a
      coercivity of about 104.9 oersted (Oe). Whereas a high conductivity of 6.5 S.m
      1was obtained at low amounts of F-NPs (40 mg). Notably, rGO/Fe3O4 composite film
      fabricated by this simple method is widely used in various fields including
      magnetoelectronics, electrochemical energy conversion and storage, and magnetic
      nanodevices and others. CONCLUSIONS: A graphene-based film deposited by Fe3O4
      nanoparticles with controllable loadings has been fabricated by a step-by-step
      heating treatment of GO/Fe3O4 colloidal solution.

PMID- 28430347
TI  - Hypopharyngeal squamous cell carcinoma and laryngeal neuroendocrine carcinoma
      colliding in the aryepiglottic fold: a case report.
AB  - PURPOSE: A collision tumor consists of 2 different histologically distinct and
      topographically independent tumors merging in the same mass. In the head and neck
      region they are rare, with only 4 cases reported in the larynx. CASE REPORT: A 60
      year-old heavy smoker complained of a left submandibular lesion in October 2014.
      The lesion was excised and showed a poorly differentiated carcinoma, suggestive
      for adenocarcinoma. After a positron emission tomography-computed tomography scan
      showed increased metabolic activity in the left laterocervical region and right
      vocal cord, the patient underwent endoscopic biopsy of the lesion of the left
      piriform sinus, which was positive for moderately differentiated squamous cell
      carcinoma (SCC). He was then submitted to circular pharyngolaryngectomy,
      reconstruction with a radial forearm free flap, and bilateral neck dissection.
      The histopathologic examination showed an in situ and microinvasive SCC of the
      left pyriform sinus colliding with a high-grade, non-small-cell neuroendocrine
      carcinoma of the larynx. CONCLUSIONS: To our knowledge, this is the first case
      described of laryngeal collision tumor comprising a neuroendocrine component. The
      choice of treatment of this kind of lesion is difficult because of the presence
      of 2 different histologies and of the controversial prognostic correlation of non
      small-cell neuroendocrine neoplasms of the head and neck region.

PMID- 28430348
TI  - Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas: a personal point
      of view.
AB  - Dr. Gianni Bonadonna is internationally recognized as one of the foremost medical
      oncologists of the 20th century. He is best known for his pioneering work in the
      development of adjuvant chemotherapy for breast cancer, but he was also the
      father of sarcoma chemotherapy. The first investigator to study the new
      chemotherapeutic agent adriamycin in the late 1960s, he noted activity against
      sarcomas. This article, focusing on adjuvant chemotherapy, adriamycin, and
      sarcomas, memorializes his achievements and their progeny.

PMID- 28430349
TI  - Prognostic significance of infiltrating immune cell subtypes in invasive ductal
      carcinoma of the breast.
AB  - PURPOSE: To explore the correlation between tumor-infiltrating immune cell
      subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102
      patients with invasive ductal carcinoma of the breast were analyzed for immune
      related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the
      3 most highly stained intratumoral stroma areas of the primary tumor was counted.
      The mean number was calculated and used to divide patients into 2 groups for each
      marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68
      high/CD68-low). RESULTS: Kaplan-Meier survival analysis showed (a) for all
      patients that high tumor-infiltrating CD8+ and CD20+ B lymphocytes, low tumor
      infiltrating FOXP3+ regulatory T cells (Tregs), and CD68+ macrophages all
      increased OS and DFS (p<0.05); (b) for both the 35 ER-negative and 45 lymph-node
      negative patients, high CD8+ cytotoxic T lymphocytes (CTLs) increased OS and DFS
      (p<0.05). Multivariate analysis of OS and DFS showed that for all patients high
      CD8+ CTLs and low FOXP3+ Tregs were related to good OS and DFS (p<0.05).
      CONCLUSION: High numbers of tumor-infiltrating CD8+ and low numbers of FOXP3+ T
      lymphocytes both could function as potential independent prognostic markers for
      invasive ductal breast carcinoma.

PMID- 28430350
TI  - 1st Evidence-based Italian consensus conference on cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy for peritoneal carcinosis from ovarian
      cancer.
AB  - Ovarian cancer (OC) remains relatively rare, although it is among the top 4
      causes of cancer death for women younger than 50. The aggressive nature of the
      disease and its often late diagnosis with peritoneal involvement have an impact
      on prognosis. The current scientific literature presents ambiguous or uncertain
      indications for management of peritoneal carcinosis (PC) from OC, both owing to
      the lack of sufficient scientific data and their heterogeneity or lack of
      consistency. Therefore, the Italian Society of Surgical Oncology (SICO), the
      Italian Society of Obstetrics and Gynaecology, the Italian Association of
      Hospital Obstetricians and Gynaecologists, and the Italian Association of Medical
      Oncology conducted a multidisciplinary consensus conference (CC) on management of
      advanced OC presenting with PC during the SICO annual meeting in Naples, Italy,
      on September 10-11, 2015. An expert committee developed questions on diagnosis
      and staging work-up, indications, and procedural aspects for peritonectomy,
      systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy for PC from
      OC. These questions were provided to 6 invited speakers who answered with an
      evidence-based report. Each report was submitted to a jury panel, representative
      of Italian experts in the fields of surgical oncology, gynecology, and medical
      oncology. The jury panel revised the reports before and after the open discussion
      during the CC. This article is the final document containing the clinical
      evidence reports and statements, revised and approved by all the authors before
      submission.

PMID- 28430351
TI  - C677T and A1298C polymorphisms of methylene tetrahydrofolate reductase in non
      Hodgkin lymphoma: southeast Iran.
AB  - PURPOSE: Polymorphisms of the methylene tetrahydrofolate reductase (MTHFR) gene
      have been reported as risk factors for non-Hodgkin lymphoma (NHL) in some
      populations. Our goal was to evaluate the potential role of A1298C and C677T
      polymorphisms of MTHFR in risk of NHL in southeast Iran. METHODS: In the present
      case-control study, 127 patients with newly diagnosed NHL along with 150
      ethnicity- and age-matched controls were examined. The A1298C and C677T
      polymorphisms were genotyped using the Tetra Amplification Refractory Mutation
      System polymerase chain reaction method. RESULTS: There were no significant
      differences in genotype frequencies between cases and controls regarding either
      A1298C polymorphism. For this polymorphism, 53.8% of the controls and 54.3% of
      the patients with NHL showed homozygous wild-type (AA) genotype. Variant 1298C
      allele was recognized with overall frequency of 34.6% in both groups. Frequencies
      of CC, CT, and TT genotypes of C677T polymorphism were observed in 73.1%, 25.8%,
      and 1.3% of the controls, and 64.5%, 33.1%, and 2.4% of the patients with NHL
      (p>0.05). In combination, CT + TT conferred a significantly higher risk of NHL
      (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.9-2.4, p = 0.03). Overall,
      variant 677T allele presented with higher frequency in the patients with NHL than
      the controls (26.7% versus 21.3%, respectively; OR 1.3, 95% CI 0.8-2.1, p>0.05).
      Although statistically insignificant, the highest risk of NHL was identified in
      patients with C677T; A1298C: CT; CC haplotype (OR 4.7, 95% CI 0.4-46.4, p = 0.1).
      CONCLUSIONS: Combination of CT and TT genotypes of C677T polymorphism conferred a
      significantly higher risk for NHL. It is recommended to investigate further the
      potential role of this polymorphism in NHL development.

PMID- 28430352
TI  - Integration between oncology and palliative care: a plan for the next decade?

PMID- 28430353
TI  - Author's reply to: Integration between oncology and palliative care: a plan for
      the next decade?

PMID- 28430354
TI  - Identification of morphogenetic capability limitations via a single starfish
      embryo/larva reconstruction method.
AB  - Reconstruction of a starfish embryo provides unique morphogenesis during the
      developmental process that is not observed in normal development. Here, we
      established a novel method for reconstruction from single embryos/larvae. By
      using this method, we investigated the morphogenetic capabilities in critical
      steps during the reconstruction process as showed by the reconstructed embryos
      generated from embryos/larvae at the six developmental stages, or from segregated
      ectodermal and/or endomesodermal cells. Additionally, the novel method addressed
      several problems found in prior methods related to reproducibly generating
      reconstructed embryos. In the reconstructions from the various stage
      embryos/larvae, the morphogenetic capabilities were substantively reduced in the
      reconstructed embryos generated from 3-day bipinnaria (3dBp). The combination
      experiments using ectodermal or endomesodermal cells segregated from 2dBp or 3dBp
      showed a reduction of the morphogenetic capabilities in both cells types in 3dBp.
      The reconstructed embryos generated from ectodermal or endomesodermal cells
      segregated from 2dBp possessed partial morphological features, such as formation
      of the epithelium or blastopore, but all failed to develop into bipinnariae.
      These results indicate two limitations of the morphogenetic capabilities during
      the reconstruction process. Firstly, the morphogenetic capabilities to
      reconstruct an embryo are considerably reduced between 2dBp and 3dBp. Secondly,
      cells specified as ectoderm or endomesoderm possess limited morphogenetic
      capabilities to reconstruct bipinnaria. Furthermore, our results demonstrate that
      the interaction between these specified cell types is required for
      reconstruction.

PMID- 28430355
TI  - Does endothelial tetrahydrobiopterin control the endothelial NO synthase coupling
      state in arterial resistance arteries?
AB  - LINKED ARTICLE: This article is a Commentary on Chuaiphichai S, Crabtree MJ,
      McNeill E, Hale AB, Trelfa L, Channon KM et al. (2017). A key role for
      tetrahydrobiopterin-dependent endothelial NOS regulation in resistance arteries:
      studies in endothelial cell tetrahydrobiopterin-deficient mice. Br J Pharmacol
      174: 657-671. https://doi.org/10.1111/bph.13728.

PMID- 28430356
TI  - CRISPR/Cas9: An RNA-guided highly precise synthetic tool for plant genome
      editing.
AB  - CRISPR/Cas9 is a newly developed and naturally occurred genome editing tool,
      which is originally used by bacteria for immune defence. In the past years, it
      has been quickly employed and modified to precisely edit genome sequences in both
      plants and animals. Compared with the well-developed zinc finger nucleases (ZFNs)
      and transcription activator-like effector nucleases (TALENs), CRISPR/Cas9 has
      lots of advantages, including easier to design and implement, higher targeting
      efficiency, and less expensive. Thus, it is becoming one of the most powerful
      tools for knockout of an individual gene as well as insertion of one gene and/or
      control of gene transcription. Studies have shown that CRISPR/Cas9 is a great
      tool to edit many genes in a variety of plant species, including the model plant
      species as well as agriculturally important crops, such as cotton, maize, wheat,
      and rice. CRISPR/Cas9-based genome editing can be used for plant functional
      studies and plant improvement to yield, quality, and tolerance to environmental
      stress.

PMID- 28430358
TI  - Regulation of axon arborization pattern in the developing chick ciliary ganglion:
      Possible involvement of caspase 3.
AB  - During a certain critical period in the development of the central and peripheral
      nervous systems, axonal branches and synapses are massively reorganized to form
      mature connections. In this process, neurons search their appropriate targets,
      expanding and/or retracting their axons. Recent work suggested that the caspase
      superfamily regulates the axon morphology. Here, we tested the hypothesis that
      caspase 3, which is one of the major executioners in apoptotic cell death, is
      involved in regulating the axon arborization. The embryonic chicken ciliary
      ganglion was used as a model system of synapse reorganization. A dominant
      negative mutant of caspase-3 precursor (C3DN) was made and overexpressed in
      presynaptic neurons in the midbrain to interfere with the intrinsic caspase-3
      activity using an in ovo electroporation method. The axon arborization pattern
      was 3-dimensionally and quantitatively analyzed in the ciliary ganglion. The
      overexpression of C3DN significantly reduced the number of branching points, the
      branch order and the complexity index, whereas it significantly elongated the
      terminal branches at E6. It also increased the internodal distance significantly
      at E8. But, these effects were negligible at E10 or later. During E6-8, there
      appeared to be a dynamic balance in the axon arborization pattern between the
      "targeting" mode, which is accompanied by elongation of terminal branches and the
      pruning of collateral branches, and the "pathfinding" mode, which is accompanied
      by the retraction of terminal branches and the sprouting of new collateral
      branches. The local and transient activation of caspase 3 could direct the
      balance towards the pathfinding mode.

PMID- 28430360
TI  - Age at cancer diagnosis may influence risk of heart disease death.

PMID- 28430361
TI  - Rare heart risk found with checkpoint inhibitors.

PMID- 28430362
TI  - CDC recommends only 2 HPV doses for younger adolescents.

PMID- 28430357
TI  - Reactive oxygen species: key regulators in vascular health and diseases.
AB  - : ROS are a group of small reactive molecules that play critical roles in the
      regulation of various cell functions and biological processes. In the vascular
      system, physiological levels of ROS are essential for normal vascular functions
      including endothelial homeostasis and smooth muscle cell contraction. In
      contrast, uncontrolled overproduction of ROS resulting from an imbalance of ROS
      generation and elimination leads to the development of vascular diseases.
      Excessive ROS cause vascular cell damage, the recruitment of inflammatory cells,
      lipid peroxidation, activation of metalloproteinases and deposition of
      extracellular matrix, collectively leading to vascular remodelling. Evidence from
      a large number of studies has revealed that ROS and oxidative stress are involved
      in the initiation and progression of numerous vascular diseases including
      hypertension, atherosclerosis, restenosis and abdominal aortic aneurysm.
      Furthermore, considerable research has been implemented to explore antioxidants
      that can reduce ROS production and oxidative stress in order to ameliorate
      vascular diseases. In this review, we will discuss the nature and sources of ROS,
      their roles in vascular homeostasis and specific vascular diseases and various
      antioxidants as well as some of the pharmacological agents that are capable of
      reducing ROS and oxidative stress. The aim of this review is to provide
      information for developing promising clinical strategies targeting ROS to
      decrease cardiovascular risks. LINKED ARTICLES: This article is part of a themed
      section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the
      other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

PMID- 28430359
TI  - Sulfur-containing gaseous signal molecules, ion channels and cardiovascular
      diseases.
AB  - : Sulfur-containing gaseous signal molecules including hydrogen sulphide and
      sulfur dioxide were previously recognized as toxic gases. However, extensive
      studies have revealed that they can be generated in the cardiovascular system via
      a sulfur-containing amino acid metabolic pathway, and have an important role in
      cardiovascular physiology and pathophysiology. Ion channels are pore-forming
      membrane proteins present in the membrane of all biological cells; their
      functions include the establishment of a resting membrane potential and the
      control of action potentials and other electrical signals by conducting ions
      across the cell membrane. Evidence has now accumulated suggesting that the sulfur
      containing gaseous signal molecules are important regulators of ion channels and
      transporters. The aims of this review are (1) to discuss the recent experimental
      evidences in the cardiovascular system regarding the regulatory effects of sulfur
      containing gaseous signal molecules on a variety of ion channels, including ATP
      sensitive potassium, calcium-activated potassium, voltage-gated potassium, L- and
      T-type calcium, transient receptor potential and chloride and sodium channels,
      and (2) to understand how the gaseous signal molecules affect ion channels and
      cardiovascular diseases. LINKED ARTICLES: This article is part of a themed
      section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the
      other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

PMID- 28430363
TI  - Cerebrolysin for acute ischaemic stroke.
AB  - BACKGROUND: Cerebrolysin is a mixture of low-molecular-weight peptides and amino
      acids derived from pigs' brain tissue, which has potential neuroprotective and
      neurotrophic properties. It is widely used in the treatment of acute ischaemic
      stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet
      countries. OBJECTIVES: To assess the benefits and risks of cerebrolysin for
      treating acute ischaemic stroke. SEARCH METHODS: In May 2016 we searched the
      Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science
      Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of
      Russian Databases. We also searched reference lists, ongoing trials registers and
      conference proceedings, and contacted the manufacturer of cerebrolysin, EVER
      Neuro Pharma GmbH (formerly Ebewe Pharma). SELECTION CRITERIA: Randomised
      controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of
      stroke onset and continued for any time, with placebo or no treatment in people
      with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors
      independently applied inclusion criteria, assessed trial quality and risk of
      bias, and extracted data. MAIN RESULTS: We identified six RCTs (1501
      participants) that met the inclusion criteria.We evaluated risk of bias and
      judged it to be unclear for generation of allocation sequence in four studies and
      low in two studies; unclear for allocation concealment in five studies and low in
      one study; high for incomplete outcome data (attrition bias) in five studies and
      unclear in one study; unclear for blinding; high for selective reporting in four
      studies and unclear in two; and high for other sources of bias in three studies
      and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company
      EVER Neuro Pharma, supported three multi-centre studies, either totally, or
      providing cerebrolysin and placebo, randomisation codes, research grants, or
      statisticians.None of the included trials reported on poor functional outcome
      defined as death or dependence at the end of the follow-up period or early death
      (within two weeks of stroke onset).All-cause death: we extracted data from five
      trials (1417 participants). There was no difference in the number of deaths:
      46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91
      95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate
      quality evidence).Serious adverse events (SAEs): there was no significant
      difference in the total number of SAEs with cerebrolysin (RR 1.16, 95% CI 0.81 to
      1.67). This comprised no difference in fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38)
      and an increase in the number of people with non-fatal SAEs (20/667 with
      cerebrolysin and 8/668 with placebo: RR 2.47, 95% CI 1.09 to 5.58, P = 0.03) (3
      trials, 1335 participants, moderate-quality evidence).Total number of people with
      adverse events: three trials reported on this. There was no difference in the
      total number of people with adverse events: 308/667 in cerebrolysin group versus
      307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3
      trials, 1335 participants, moderate-quality evidence). AUTHORS' CONCLUSIONS: The
      findings of this Cochrane Review do not demonstrate clinical benefits of
      cerebrolysin for treating acute ischaemic stroke. We found moderate-quality
      evidence of an increase in non-fatal SAEs with cerebrolysin use but not in total
      SAEs.

PMID- 28430364
TI  - The effects of cognitive-behavioral therapy for eating disorders on quality of
      life: A meta-analysis.
AB  - OBJECTIVE: Meta-analyses have documented the efficacy of cognitive-behavioral
      therapy (CBT) for reducing symptoms of eating disorders. However, it is not known
      whether CBT for eating disorders can also improve quality of life (QoL). This
      meta-analysis therefore examined the effects of CBT for eating disorders on
      subjective QoL and health-related quality of life (QoL). METHOD: Studies that
      assessed QoL before and after CBT for eating disorders were searched in the
      PsycInfo and Medline database. Thirty-four articles met inclusion criteria.
      Pooled within and between-groups Hedge's g were calculated at post-treatment and
      follow-up for treatment changes on both subjective and HRQoL using a random
      effects model. RESULTS: CBT led to significant and modest improvements in
      subjective QoL and HRQoL from pre to post-treatment and follow-up. CBT led to
      greater subjective QoL improvements than inactive (i.e., wait-list) and active
      (i.e., a combination of bona fide therapies, psychoeducation) comparisons. CBT
      also led to greater HRQoL improvements than inactive, but not active,
      comparisons. Prepost QoL improvements were larger in studies that delivered CBT
      individually and by a therapist or according to the cognitive maintenance model
      of eating disorders (CBT-BN or CBT-E); though this was not replicated at follow
      up CONCLUSIONS: Findings provide preliminary evidence that CBT for eating
      disorders is associated with modest improvements in QOL, and that CBT may be
      associated with greater improvements in QOL relative to comparison conditions.

PMID- 28430365
TI  - Brain gyrification and neuroprogression in bipolar disorder.

PMID- 28430366
TI  - Cyclic-RGD penta-peptides cRGDyK derivatized with cyclopentadienyl complexes of
      technetium and rhenium as radiopharmaceutical probes.
AB  - The present study reports the syntheses of half-sandwich complexes of the type
      [M(eta5 -C5 H4 CONH-R)(CO)3 ] (M?Re,99m Tc;R?cyclic RGD peptide (cRGDyK) for
      potential imaging of alphav beta3 integrin expression. The 99m Tc complex was
      prepared directly from the reaction of [99m Tc(OH2 )3 (CO)3 ]+ with cRGDyK,
      doubly conjugated to Thiele's acid [(C5 H5 COOH)2 ] in water. This approach
      extends the viability of metal-mediated retro Diels-Alder reactions for the
      preparation of small molecules such as linear tripeptides to a more complex
      cyclic peptide carrying a [(eta5 -C5 H4 )99m Tc(CO)3 ] tag. The Diels-Alder
      product [(C5 H5 CONH-cRGDyK)2 ] was prepared from Thiele's acid via double
      peptide coupling. The Re-complex [Re(eta5 -C5 H4 CONH-cRGDyK)(CO)3 ] was obtained
      by attaching [Re(eta5 -C5 H4 COOH)(CO)3 ] directly to the N-terminus of cRGDyK.
      The identity of the 99m Tc-complex is confirmed by chromatographic comparison
      with the corresponding rhenium complex, fully characterized by spectroscopic
      techniques.

PMID- 28430367
TI  - Effect of dalteparin administration on thrombin generation kinetics in healthy
      dogs.
AB  - BACKGROUND: Dalteparin is used to prevent thrombotic complications in dogs.
      Measurement of anti-factor Xa (anti-FXa) activity is currently used for
      monitoring therapy, but remains a nonfunctional test. The calibrated automated
      thrombogram (CAT) could be a suitable approach for functional monitoring.
      OBJECTIVES: We hypothesized that the CAT will detect decreased endogenous
      thrombin potential (ETP) in healthy dogs receiving dalteparin. METHODS: Twenty
      four healthy adult Beagles were randomly allocated to 4 equal groups. A single
      subcutaneous (SC) dose of 50 U/kg, 100 U/kg, or 150 U/kg of dalteparin was given.
      Platelet-poor plasma (PPP) was collected over a 24-hour period and evaluated by
      thrombin generation (TG) via CAT, anti-FXa activity, and APTT. Analysis was
      performed with a repeated-measures general linear mixed model, and the treated
      groups were compared to a placebo group. RESULTS: Time, dose, and time-dose
      interaction significantly affected ETP (P < .0001 for all effects), peak (P <
      .0001 for all effects), rate index (P < .0006 for all effects), and anti-FXa
      activity (P < .0001 for all effects). No significant time trend was detected in
      the control group. Dogs receiving the 100 U/kg dalteparin SC injection showed the
      most homogeneous response of ETP inhibition among treated groups. The %
      inhibition of ETP from baseline increased nonlinearly as a function of anti-FXa
      activity (r2 = .8186). CONCLUSIONS: The CAT assay can be employed to measure the
      effects of dalteparin at different doses in healthy dogs, showing sensitivity to
      time- and dose-dependent changes in ETP and other TG variables. Further
      investigation of the CAT as a tool for monitoring low molecular weight heparin
      therapy in dogs is warranted.

PMID- 28430368
TI  - Proteomic Data in Morphine Addiction Versus Real Protein Activity: Metabolic
      Enzymes.
AB  - Drug dependence is an escalating problem worldwide and many efforts are being
      made to understand the molecular basis of addiction. The morphine model is widely
      used in these investigations. To date, at least 29 studies exploring the
      influence of morphine on mammals' proteomes have been published. Among various
      proteins indicated as up- or down-regulated, the expression changes of enzymes
      engaged in energy metabolism pathways have often been confirmed. To verify
      whether proteomics-indicated alterations in enzyme levels reflect changes in
      their activity, four enzymes: PK, MDH, Complex I, and Complex V were investigated
      in morphine addiction and abstinence models. After analyses of the rat brain
      mitochondria fraction in the model of morphine dependence, we found that one of
      the investigated enzymes (pyruvate kinase) showed statistically significant
      differences observed between morphine, control, and abstinence groups. J. Cell.
      Biochem. 118: 4323-4330, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28430369
TI  - Quantitative segmental analysis of myocardial perfusion to differentiate stress
      cardiomyopathy from acute myocardial infarction: A myocardial contrast
      echocardiography study.
AB  - BACKGROUND: Both stress cardiomyopathy (SCMP) and acute myocardial infarction
      (AMI) present with similar clinical symptoms and signs, and apical akinesis.
      HYPOTHESIS: Quantitative segmental analysis of myocardial contrast
      echocardiography (MCE) helps to differentiate AMI from SCMP. METHODS: Real-time
      MCE was performed in 33 consecutive patients who presented with an acute
      symptom/sign and a new apical akinesis on echocardiography. In 18 left
      ventricular (LV) myocardial segments, a replenishment curve was obtained in each
      segment to measure peak plateau myocardial contrast intensity (MCI) (A) and the
      replenishment curve slope (beta). The calibrated MCI was also measured in each
      segment. RESULTS: Among 33 patients, 22 were diagnosed with SCMP and 11 were
      diagnosed with AMI according to comprehensive diagnostic criteria. A, beta,
      Abeta, and the calibrated MCI were lower in akinetic than in normokinetic
      segments in both the SCMP and AMI groups. In the akinetic segments, A, beta,
      Abeta, and the calibrated MCI in SCMP patients were each higher than those in AMI
      patients. In patient-based analyses, areas under the ROC curves of A, beta,
      Abeta, and the calibrated MCI for diagnosing AMI were 0.769, 0.607, 0.822, and
      0.934, respectively. The optimal cutoff values to diagnose AMI were Abeta < 3.7
      dB/sec (sensitivity 82%, specificity 82%) and a calibrated MCI < -23 dB
      (sensitivity 91%, specificity 95%). CONCLUSIONS: Although myocardial perfusion is
      relatively reduced in the akinetic segments of SCMP, a quantitative segmental
      analysis of myocardial perfusion using MCE helps to discriminate AMI from SCMP.

PMID- 28430370
TI  - Extremely low frequency electromagnetic field (ELF-EMF) reduces oxidative stress
      and improves functional and psychological status in ischemic stroke patients.
AB  - As a result of ischaemia/reperfusion, massive generation of reactive oxygen
      species occurs, followed by decreased activity of antioxidant enzymes. Extremely
      low frequency electromagnetic fields (ELF-EMF) can modulate oxidative stress, but
      there are no clinical antioxidant studies in brain stroke patients. The aim of
      our study was to investigate the effect of ELF-EMF on clinical and antioxidant
      status in post-stroke patients. Fifty-seven patients were divided into two
      groups: ELF-EMF and non-ELF-EMF. Both groups underwent the same 4-week
      rehabilitation program. Additionally, the ELF-EMF group was exposed to an ELF-EMF
      field of 40 Hz, 7 mT for 15 min/day for 4 weeks (5 days a week). The activity of
      catalase and superoxide dismutase was measured in hemolysates, and total
      antioxidant status (TAS) determined in plasma. Functional status was assessed
      before and after the series of treatments using Activities of Daily Living (ADL),
      Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS).
      Applied ELF-EMF significantly increased enzymatic antioxidant activity; however,
      TAS levels did not change in either group. Results show that ELF-EMF induced a
      significant improvement in functional (ADL) and mental (MMSE, GDS) status.
      Clinical parameters had positive correlation with the level of enzymatic
      antioxidant protection. Bioelectromagnetics. 38:386-396, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28430371
TI  - Evaluation of circulating zonulin as a potential marker in the pathogenesis of
      nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging
      from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving
      to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold
      standard modality for diagnosing and staging NAFLD. The linkage between
      intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin
      in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD
      pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy,
      as well as 20 healthy controls were tested. Liver function tests, serum glucose,
      fasting insulin, C peptide, lipid profile, homeostasis model assessment of
      insulin resistance (HOMA-IR), IL-6, and circulating zonulin were performed to all
      subjects. Aspartate transaminase (AST), alanine transaminase (ALT), gamma
      glutamyl transferase (GGT), triglycerides, HDL-c, fasting insulin, C peptide,
      HOMA-IR, IL-6, and serum zonulin were higher in NAFLD group than in controls (p <
      0.05), and in NASH patients than those with simple steatosis (p < 0.05). Zonulin
      was positively correlated with body mass index (BMI), ALT, triglycerides, fasting
      insulin, HOMA-IR, liver histopathology, and serum IL-6 (p < 0.05), with inverse
      correlation to HDL-C (p < 0.05). At cut off 8.3 pc/mL, serum zonulin was found to
      be of diagnostic value of NASH occurrence with 100% sensitivity and specificity
      (AUR = 1.000, p-value = <0.001). The increasing zonulin levels in NAFLD patients
      with steep rise in NASH group denotes a possible role in pathogenesis of NAFLD
      occurrence and progression. This could open a new avenue of implicating zonulin
      antagonists as targeted therapies in NAFLD prevention.

PMID- 28430372
TI  - Retinal nerve fibre layer thickness is reduced in metabolic syndrome.
AB  - AIMS: To investigate retinal nerve fibre layer (RNFL) thickness in people with
      metabolic syndrome (MetS) and healthy controls. METHODS: A cross-sectional study
      was performed from March 2014 to January 2016. All participants underwent
      anthropometric and serological biochemical measurements, ophthalmological
      examination, and spectral-domain optical coherence tomography (SD-OCT).
      Individuals with elevated intraocular pressure, glaucoma, diabetic retinopathy
      and other ocular disorders were excluded. T-test, Chi square and general linear
      models were used to analyse the data. RESULTS: In total, 278 eyes from 139
      participants were investigated [median (interquartile range) age: 37 (32-43)
      years]. RNFL thickness was lower in the nasal superior (107.8 +/- 19.5MUm) and
      temporal superior (135.7 +/- 18.9MUm) sectors in MetS group compared with the
      control group (114.6 +/- 22.4 MUm, P = 0.013 and 140.7 +/- 18.2 MUm, P = 0.027,
      respectively). After multiple adjustments for age, gender and the side of the
      examined [right (OD)/left (OS)] eye, MetS was independently associated with a
      lower RFNL thickness in the nasal superior (beta = 0.20, P = 0.009) and temporal
      superior (beta = 0.14, P = 0.048) sectors. RNFL thickness was significantly
      reduced in participants with higher numbers of metabolic abnormalities,
      independent of age, gender and the side of the examined eye (P = 0.043).
      CONCLUSION: Our findings demonstrate that MetS is independently associated with
      reduced RNFL thickness, suggesting that neurodegeneration is implicated in
      pathogenesis of MetS.

PMID- 28430373
TI  - A five-miRNA expression signature predicts survival in hepatocellular carcinoma.
AB  - The aim of this study was to identify a microRNA (miRNA) expression signature for
      predicting HCC (hepatocellular carcinoma) survival. A total of 322 HCC patients
      in The Cancer Genome Atlas (TCGA) database were randomly divided into training
      and testing set. miRNAs, associated with survival time in the training set, were
      identified by using univariate Cox regression analysis. The risk score was
      formulated based on the expression levels of these miRNAs. Then the miRNA
      signature was validated in testing set through Kaplan-Meier analysis and log-rank
      test. hsa-miR-301a, hsa-miR-132, hsa-miR-212, hsa-miR-489, and hsa-miR-1468 were
      identified to formulate risk score in training set and used to calculate the risk
      score of each patients in testing set. About 161 patients in testing set were
      segregated into high- and low-risk group according to the median risk score. The
      survival time of high-risk group was significantly shorter (p = 0.0248) than low
      risk group in testing test. The target genes of five miRNAs were significantly
      enriched in valine, leucine, and isoleucine degradation pathway and PPAR
      signaling pathway. hsa-miR-1468 had an up-regulated tendency in HCC tissues
      compared to adjacent tumor tissues. The expression of hsa-miR-301a, hsa-miR-132,
      hsa-miR-212, hsa-miR-489, and hsa-miR-1468, which might be potential biomarkers
      to evaluate HCC patients' prognosis.

PMID- 28430374
TI  - Scope of the Thermal Ring-Expansion Reaction of Boroles with Organoazides.
AB  - Electronic and steric factors have been investigated in the thermal ring
      expansion of boroles with organic azides, a reaction that provides access to
      highly arylated 1,2-azaborinines, BN analogues of benzene. Reactions of a variety
      of boroles and organic azides demonstrate that the synthetic method is quite
      general in furnishing 1,2-azaborinines, but the respective reaction rates reveal
      a strong dependence on the substituents on the two reactants. The products have
      been characterized by UV/Vis, electrochemical, NMR, and X-ray diffraction
      methods, clarifying their constitutions and highlighting substituent effects on
      the electronic structure of the 1,2-azaborinines. Furthermore, analysis of
      several possible mechanistic pathways for 1,2-azaborinine formation, as studied
      by DFT, revealed that a two-step mechanism involving azide-borole adduct
      formation and nitrene insertion is favored.

PMID- 28430375
TI  - Electrochemical Water Oxidation Catalyzed by an In Situ Generated alpha-Co(OH)2
      Film on Zeolite-Y Surface.
AB  - The design and synthesis of an efficient and robust water-oxidation catalyst with
      inexpensive materials remains an important challenge in the context of artificial
      photosynthesis. Herein, a simple but unique technique is reported to in situ
      generate a thin-film of alpha-Co(OH)2 on the surface of zeolite-Y [hereafter
      referred to as Y-alpha-Co(OH)2 ] that acts as an efficient and stable catalyst
      for electrochemical water oxidation in alkaline medium. Catalyst Y-alpha-Co(OH)2
      is so stable that it retains its catalytic activity even after 2000 cyclic
      voltammetric cycles of water oxidation. Expectedly, the chemical composition of
      alpha-Co(OH)2 on the surface of zeolite-Y remains same as that of parent Y-alpha
      Co(OH)2 after 2000 electrocatalytic cycles. A Tafel slope as low as 59 mV decade
      1 in 0.1 m KOH (pH 13) suggests faster oxygen evolution kinetics
      (overpotential=329 mV; turnover frequency=0.35 mol O2 (mol Co)-1  s-1 at 1 mA cm
      2 ) than the existing alpha-Co(OH)2 -based electrocatalysts operating in alkaline
      medium.

PMID- 28430376
TI  - Acute generalized exanthematous pustulosis associated with ipilimumab and
      nivolumab.

PMID- 28430377
TI  - Exploring why young people with Type 1 diabetes decline structured education with
      a view to overcoming barriers.
AB  - AIMS: To identify factors that influence lack of engagement of young adults with
      Type 1 diabetes (aged 13-21 years) with structured diabetes education (SDE) to
      inform and broaden the reach of future SDE. METHODS: A quantitative, cross
      sectional survey was undertaken of 227 young people with Type 1 diabetes drawn
      from 11 health trusts across Northern Ireland and England, deemed to be
      representative of the wider population. Participants were asked to complete a
      questionnaire exploring non-attendance, along with the Diabetes Care Profile, the
      Diabetes Empowerment Scale (Short Form), the Diabetes Knowledge Test and the 12
      item General Health Questionnaire. Demographic, health and diabetes-specific
      variables including HbA1c were also collected. RESULTS: The five most commonly
      cited reasons for non-attendance were 'Had other things to do' (68.3%), 'No time'
      (62.2%), 'Could not get time off school/college or work' (60.8%), 'Learnt about
      diabetes from other sources' (55.5%) and 'Feel able to cope on own' (52.9%).
      CONCLUSIONS: Greater emphasis is required on communication with young people
      about the benefits of SDE. In addition, efforts need to be directed to making
      diabetes education more accessible without losing the quality of structured
      programmes.

PMID- 28430378
TI  - Treating Paget's Disease-Why and How Much?

PMID- 28430379
TI  - 17 O MRS assesses the effect of mild hypothermia on oxygen consumption rate in
      tumors.
AB  - Although oxygen consumption is a key factor in metabolic phenotyping, its
      assessment in tumors remains critical, as current technologies generally display
      poor specificity. The objectives of this study were to explore the feasibility of
      direct 17 O nuclear magnetic resonance (NMR) spectroscopy to assess oxygen
      metabolism in tumors and its modulations. To investigate the impact of
      hypometabolism induction in the murine fibrosarcoma FSAII tumor model, we
      monitored the oxygen consumption of normothermic (37 degrees C) and hypothermic
      (32 degrees C) tumor-bearing mice. Hypothermic animals showed an increase in
      tumor pO2 (measured by electron paramagnetic resonance oximetry) contrary to
      normothermic animals. This was related to a decrease in oxygen consumption rate
      (assessed using 17 O magnetic resonance spectroscopy (MRS) after the inhalation
      of 17 O2 -enriched gas). This study highlights the ability of direct 17 O MRS to
      measure oxygen metabolism in tumors and modulations of tumor oxygen consumption
      rate.

PMID- 28430380
TI  - Thermo-Chromium: A Contactless Optical Molecular Thermometer.
AB  - The unparalleled excited-state potential-energy landscape of the chromium(III)
      based dye [1]3+ ([Cr(ddpd)2 ]3+ ; ddpd=N,N'-dimethyl-N,N'-dipyridin-2-yl-pyridin
      2,6-diamine) enables a strong dual emission in the near infrared region. The
      temperature dependence of this dual emission allows the use of [1]3+ as an
      unprecedented molecular ratiometric thermometer in the 210-373 K temperature
      range in organic and in aqueous media. Incorporation of [1]3+ in biocompatible
      nanocarriers, such as 100 nm-sized polystyrene nanoparticles and solutol
      micelles, provides nanodimensional thermometers operating under physiological
      conditions.

PMID- 28430381
TI  - Continuous subcutaneous insulin infusion (CSII) therapy at Derby Teaching
      Hospitals: sustained benefits in glucose control.
AB  - AIM: In the short term, continuous subcutaneous insulin infusion (CSII) has been
      associated with improved glycaemic control, reduced hypoglycaemia and improved
      quality of life (QOL). However, limited data are available on its long-term
      benefits, particularly in the UK. We aimed to assess the impact of CSII on longer
      term outcomes. METHOD: Patient-level data were obtained for CSII users at Derby
      Teaching Hospitals, UK. Patient confidence and satisfaction questionnaires using
      the Likert scale were used to assess confidence in self-management. Comparative
      statistics were conducted using Pearson's chi-square and Student's t-tests.
      RESULTS: Some 258 CSII users were identified (60.1% female, mean age 43.9 +/-
      13.4 years). Overall, there was significant decrease in HbA1c from 78 mmol/mol
      (9.3 +/- 2.0%) at baseline, to 69 mmol/mol (8.5 +/- 1.3%) at 6 months [mean
      difference (md): -0.64; 95% confidence interval (95% CI): -0.91 to -0.37; P <
      0.0001]; which was sustained at 6 years of follow-up (HbA1c : 66 mmol/mol, 8.2 +/
      1.3%; md: -1.07%; 95% CI: -1.45 to -0.69; P < 0.0001). One hundred and twenty
      one patients (47%) responded to the survey, of whom 95 (78.5%) reported a
      reduction in the frequency of hypoglycaemia; 102 (84.3%) were satisfied with the
      quality of care received in the insulin pump service. CONCLUSION: CSII therapy
      led to a sustained long-term improvement in glycaemic control in addition to a
      reduction in self-reported hypoglycaemia.

PMID- 28430382
TI  - Mixed evidence for the erosion of intertactical genetic correlations through
      intralocus tactical conflict.
AB  - Alternative reproductive tactics, whereby members of the same sex use different
      tactics to secure matings, are often associated with conditional intrasexual
      dimorphisms. Given the different selective pressures on males adopting each
      mating tactic, intrasexual dimorphism is more likely to arise if phenotypes are
      genetically uncoupled and free to evolve towards their phenotypic optima.
      However, in this context, genetic correlations between male morphs could result
      in intralocus tactical conflict (ITC). We investigated the genetic architecture
      of male dimorphism in bulb mites (Rhizoglyphus echinopus) and earwigs (Forficula
      auricularia). We used half-sibling breeding designs to assess the heritability
      and intra/intersexual genetic correlations of dimorphic and monomorphic traits in
      each species. We found two contrasting patterns; F. auricularia exhibited low
      intrasexual genetic correlations for the dimorphic trait, suggesting that the ITC
      is moving towards a resolution. Meanwhile, R. echinopus exhibited high and
      significant intrasexual genetic correlations for most traits, suggesting that
      morphs in the bulb mite may be limited in evolving to their optima. This also
      shows that intrasexual dimorphisms can evolve despite strong genetic constraints,
      contrary to current predictions. We discuss the implications of this genetic
      constraint and emphasize the potential importance of ITC for our understanding of
      intrasexual dimorphisms.

PMID- 28430383
TI  - Assessment of disease-specific knowledge in Australian children with inflammatory
      bowel disease and their parents.
AB  - AIMS: Disease-specific knowledge may influence disease outcome and quality of
      life in children with inflammatory bowel disease (IBD). This prospective study
      aimed to define IBD-related knowledge in a group of Australian children with IBD
      and their parents using a validated measure of disease-specific knowledge, the
      Inflammatory Bowel Disease Knowledge Inventory Device (IBD-KID). METHODS:
      Children (less than 18 years) diagnosed with IBD who were members of the
      Australian patient support organisation were identified. Each family was sent
      copies of the IBD-KID. Children aged 10-18 years and all parents were asked to
      complete the IBD-KID and to also provide demographic details and disease
      characteristics. RESULTS: Replies were received from 196 families: 262 parents
      and 128 children completed questionnaires. Most children had a diagnosis of Crohn
      disease (65%) and 51% were male. Children diagnosed in the preceding 6 years
      scored higher than those with longer time since diagnosis. Parents had better
      scores in the IBD-KID than the children (P < 0.0001). Overall, parents and
      children had poor understanding of key management issues for IBD (such as side
      effects of steroids), important outcomes (e.g. growth) and the use of
      complementary therapies. CONCLUSIONS: Consistent patterns of IBD-related
      knowledge were noted in this large group of Australian children with IBD and
      their parents. Measurement of disease-related knowledge with the IBD-KID can
      identify gaps in understanding, thereby permitting focused educational
      activities. Although these knowledge gaps may impact upon outcomes, further
      prospective studies are now required to elucidate the relationships between
      enhanced knowledge and specific outcomes.

PMID- 28430384
TI  - Pharmacokinetics of concentrated naloxone nasal spray over first 30 minutes post
      dosing: analysis of suitability for opioid overdose reversal.
AB  - BACKGROUND AND AIMS: Lack of non-injectable naloxone formulations has impeded
      widespread take-home provision for the prevention of heroin/opioid overdose
      deaths. For non-injectable formulations that are finally being investigated,
      rapid onset of action and sufficient bioavailability will be vital. We present
      analysis of data from a study of concentrated naloxone nasal spray formulations.
      Our aims are: to assess (1) pharmacokinetic properties and (2) suitability for
      overdose reversal in terms of naloxone absorption within 30 minutes post-dosing.
      DESIGN AND INTERVENTIONS/COMPARATOR: Open-label, randomized, four-way cross-over
      Latin-square pharmacokinetic study of naloxone administration by three routes:
      intranasal at two doses (8 mg/0.4 ml, 16 mg/0.4 ml) versus sublingual (16 mg/ml)
      versus intravenous reference (1 mg/ml). SETTING: Clinical Pharmacology Unit at
      The Ohio State University (Columbus, OH, USA). PARTICIPANTS: Twelve healthy
      volunteers (age 20-41; seven female). MEASUREMENTS: From blood plasma naloxone
      concentrations, (1) standard pharmacokinetic parameters, including maximum plasma
      concentration (Cmax ) and mean absolute bioavailability (F%, relative to
      intravenous injection), were determined; as well as (2) partial area under the
      curve (AUC) values, tmax (time to maximum plasma concentration) and t50% (time to
      50% of maximum plasma concentration) as measures of early absorption. FINDINGS:
      (1) Bioavailability was F% = 25-28% for intranasal naloxone. Sublingual had low
      bioavailability (F% = 2%) and was not considered further. Mean Cmax values for 8
      mg (12.83 ng/ml) and 16 mg (18.25 ng/ml) intranasal exceeded 1 mg intravenous
      (9.64 ng/ml) naloxone. (2) Following intranasal administration, t50% was reached
      within 8 minutes and tmax within 20 minutes. Mean naloxone absorption from dosing
      to 30 minutes (AUC30 ) was greater following 8 mg (4.17 h * ng/ml) and 16 mg
      (5.91 h * ng/ml) intranasal than following 1 mg intravenous (1.70 h * ng/ml)
      administration. CONCLUSIONS: Concentrated naloxone nasal spray has a promising
      pharmacokinetic profile, with substantial bioavailability. Its early absorption
      time-course suggests that concentrated nasal naloxone is suitable for emergency
      administration in the community, where rapid restoration of respiratory function
      is essential for opioid overdose reversal.

PMID- 28430385
TI  - Significant reductions in alcohol use after hepatitis C treatment: results from
      the ANRS CO13-HEPAVIH cohort.
AB  - BACKGROUND AND AIMS: Few data exist on changes to substance use patterns before
      and after hepatitis C virus (HCV) treatment. We used longitudinal data of HIV-HCV
      co-infected individuals to examine whether receiving pegylated interferon (Peg
      IFN)-based therapy irrespective of HCV clearance could modify tobacco, cannabis
      and alcohol use. DESIGN: A prospective cohort of HIV-HCV co-infected individuals
      was enrolled from 2006. Participants' clinical data were retrieved from medical
      records and socio-demographic and behavioural characteristics were collected by
      yearly self-administered questionnaires. SETTING: Data were collected across 17
      hospitals in France. PARTICIPANTS: All HIV-HCV co-infected patients who initiated
      HCV treatment during follow-up and answered items regarding substance use in at
      least one yearly questionnaire (258 patients, 671 visits). INTERVENTION: HCV
      treatment consisted of Peg-IFN-based regimens. MEASUREMENTS: Four time-varying
      outcomes: hazardous alcohol use (Alcohol Use Disorders Identification Test-C >
      3/4 for women/men), number of alcohol units/month, binge drinking, cannabis and
      tobacco use. Mixed models assessed the effect of HCV treatment status (not yet
      treated, treated and HCV-cleared, treated and HCV-chronic) on each outcome.
      FINDINGS: A significant decrease (more than 60% reduction) in both hazardous
      alcohol use and binge drinking and a reduction of 10 alcohol units/month was
      observed after HCV treatment (irrespective of HCV clearance). No significant
      effect of HCV treatment status was found on tobacco use and regular cannabis use,
      but HCV 'clearers' reported less non-regular use of cannabis. CONCLUSIONS:
      Hepatitis C virus (HCV) treatment appears to help HIV-HCV co-infected patients
      reduce alcohol use.

PMID- 28430386
TI  - Peptidome Analysis of Human Serum From Normal and Preeclamptic Pregnancies.
AB  - Preeclampsia is a kind of disease that severely harms the health of pregnant
      women and infants. To better understand the molecular mechanisms involved in
      preeclampsia, we used liquid chromatography-mass spectrometry/mass spectrometry
      (LC-MS/MS) to construct a comparative peptidomic profiling of human serum between
      normal and preeclamptic pregnancies. A total of 201 peptides were confidently
      identified, with 21 up-regulated and three down-regulated. Further analysis
      indicated that these differentially expressed peptides correlate with enzyme
      regulator activity, biological regulation, and coagulation cascades occurring
      during pathological changes of preeclampsia. The identification of key peptides
      in serum may serve not only as a basis for better understanding and further
      exploring the etiology and pathogenesis of PE, but also as potential biomarkers
      and in providing targets for future therapy in PE, especially in early onset
      severe PE (sPE). J. Cell. Biochem. 118: 4341-4348, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28430387
TI  - Age-related reduction in the expression of FOXO transcription factors and
      correlations with intervertebral disc degeneration.
AB  - Aging is a main risk factor for intervertebral disc (IVD) degeneration, the main
      cause of low back pain. FOXO transcription factors are important regulators of
      tissue homeostasis and longevity. Here, we determined the expression pattern of
      FOXO in healthy and degenerated human IVD and the associations with IVD
      degeneration during mouse aging. FOXO expression was assessed by
      immunohistochemistry in normal and degenerated human IVD samples and in cervical
      and lumbar IVD from 6-, 12-, 24-, and 36-month-old C57BL/6J mice. Mouse spines
      were graded for key histological features of disc degeneration in all the time
      points and expression of two key FOXO downstream targets, sestrin 3 (SESN3) and
      superoxide dismutase (SOD2), was assessed by immunohistochemistry. Histological
      analysis revealed that FOXO proteins are expressed in all compartments of human
      and mouse IVD. Expression of FOXO1 and FOXO3, but not FOXO4, was significantly
      deceased in human degenerated discs. In mice, degenerative changes in the lumbar
      spine were seen at 24 and 36 months of age whereas cervical IVD showed increased
      histopathological scores at 36 months. FOXO expression was significantly reduced
      in lumbar IVD at 12-, 24-, and 36-month-old mice and in cervical IVD at 36-month
      old mice when compared with the 6-month-old group. The reduction of FOXO
      expression in lumbar IVD was concomitant with a decrease in the expression of
      SESN3 and SOD2. These findings suggest that reduced FOXO expression occurs in
      lumbar IVD during aging and precedes the major histopathological changes
      associated with lumbar IVD degeneration. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 35:2682-2691, 2017.

PMID- 28430388
TI  - Associations between childhood maltreatment and non-medical use of prescription
      drugs among Chinese adolescents.
AB  - AIMS: To test, among Chinese adolescents: (1) whether childhood maltreatment is
      associated with non-medical use of prescription drugs (NMUPD) and (2) whether
      there are interaction effects of childhood maltreatment and depressive symptoms
      on NMUPD. DESIGN: A secondary analysis of the cross-sectional data collected from
      7th- and 12th-graders who were sampled using a multi-stage, stratified-cluster,
      random-sampling method in the 2015 School-based Chinese Adolescents Health Survey
      (SCAHS). SETTING: Surveys conducted in high schools in six cities of China in
      2015. PARTICIPANTS: There were 24 457 students who were invited to participate
      and 23 039 students' questionnaires were completed and qualified for our survey.
      MEASUREMENTS: The outcomes comprised self-report of NMUPD (prior 30 days); a
      history of childhood maltreatment was our main predictor. Other covariates
      included depressive symptoms, smoking, drinking and demographics. Data were
      analysed using multi-level regression modelling. FINDINGS: Our final
      multivariable logistic regression models demonstrated that after adjusting for
      other variables, physical abuse was associated positively with non-medical use of
      opioids [adjusted odds ratio (AOR) = 1.13, 95% confidence interval (CI) = 1.10
      1.22], sedatives (AOR = 1.11, 95% CI = 1.10-1.21) and any prescription drugs (AOR
      = 1.13, 95% CI = 1.09-1.20); emotional abuse, sexual abuse and emotional neglect
      were also associated with an increased risk of opioids, sedatives and any
      prescription drugs misuse; students who reported that they had experienced
      childhood physical neglect were more likely to be involved in the non-medical use
      of sedatives (AOR = 1.08, 95% CI = 1.04-1.12) and any prescription drugs (AOR =
      1.06, 95% CI = 1.03-1.10). Additionally, there was no evidence of interaction
      effects on NMUPD between depressive symptoms and each of physical abuse,
      emotional abuse, sexual abuse, physical neglect and emotional neglect,
      respectively. CONCLUSIONS: Maltreatment while a child is associated with an
      increased risk of non-medical use of prescription drugs (NMUPD) among Chinese
      adolescents. The interactions of maltreatment while a child and depressive
      symptoms do not appear to be associated significantly with NMUPD among Chinese
      adolescents.

PMID- 28430389
TI  - Combination of Carmustine and Selenite Inhibits EGFR Mediated Growth Signaling in
      Androgen-Independent Prostate Cancer Cells.
AB  - Although aberrant androgen receptor (AR) signaling is a central mechanism for
      castration resistant prostate cancer (CRPC) progression, AR-independent growth
      signaling is also present in CRPC. The current therapeutic options for patients
      with CRPC are limited and new drugs are desperately needed to eliminate these
      crucial growth signaling pathways. We have previously shown that combination of
      carmustine and selenite effectively induces apoptosis and growth inhibition by
      targeting AR and AR-variants in CRPC cells. High levels of EGFR expression
      present in the CRPC cells mediates the cell proliferation via AR-independent
      growth signaling mechanisms. Therefore, in this study, we investigated whether
      the combination of carmustine and selenite could inhibit EGFR mediated growth
      signaling and induce apoptosis in androgen independent-AR negative prostate
      cancer cells. EGF exposure dose and time dependently increased phospho-EGFR
      (Tyr845, Tyr1068, and Tyr1045), pAkt (Ser473), and pERK1/2 (Thr204/Tyr202)
      protein expression levels in AIPC cells. Combination of carmustine and selenite
      treatment markedly suppressed EGF-stimulated proliferation and survival of AIPC
      cells and effectively induced apoptosis. The ROS generated by the combination of
      carmustine and selenite exhibited a strong inhibition on EGF stimulated EGFR and
      its downstream signaling molecules such as Akt, NF-kB, ERK1/2, and Cyclin D1.
      Individual agent treatment showed only partial effect. Overall, our findings
      demonstrated that the combination of carmustine and selenite treatment
      dramatically inhibits EGFR signaling, proliferation, and induces apoptosis in
      AIPC cells, suggesting a potential candidate for the treatment of CRPC. The
      results of the study further suggest that the combination of carmustine and
      selenite treatment can overcome EGFR mediated AR-independent growth response in
      CRPC during anti-androgen therapy. J. Cell. Biochem. 118: 4331-4340, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28430390
TI  - Chronic toxicity of binary-metal mixtures of cadmium and zinc to Daphnia magna.
AB  - The present study characterized the chronic effect of binary-metal mixtures of
      cadmium (Cd) and zinc (Zn) on Daphnia magna. The titration design was chosen to
      characterize the 21-d chronic effects of the binary-metal mixtures on survival,
      growth, reproduction, and metal accumulation in D. magna. Using this design,
      increasing concentrations of Zn (10, 20, 40, 80, 120, 160, and 200 MUg/L) were
      titrated against a constant concentration of 1.5 MUg/L Cd. The results
      demonstrated that Cd was highly toxic to D. magna. In a mixture with Cd and Zn,
      sublethal concentrations of 10 and 20 MUg/L Zn were insufficient to protect D.
      magna from chronic Cd toxicity, whereas mixtures containing 40, 80, and 120 MUg/L
      Zn provided strong protective effects to D. magna at all endpoints and resulted
      in less-than-additive effects. At higher Zn concentrations, such as 160 and 200
      MUg/L, Zn appeared to contribute to the toxicity. The less-than-additive effects
      observed in the Cd-Zn mixture can be explained by the decrease in body Cd
      concentration when the Zn concentration was increased in the exposure media.
      Embryos analyzed for morphological alterations in the Cd-Zn mixtures demonstrated
      severe developmental defects. The effect of Cd on undeveloped embryos while both
      Zn and Cd are present in the organisms raises a question of whether the
      competitive binding mechanism of Zn and Cd is still happening at the cellular
      level in the organisms. The results of the present study are useful for
      development of the biotic ligand model and environmental quality guidelines for
      metal mixtures. Environ Toxicol Chem 2017;36:2739-2749. (c) 2017 SETAC.

PMID- 28430391
TI  - Analysis of pulmonary embolus size at the time of recurrence compared with
      presentation: a single-centre retrospective study.
AB  - : Essentials Size of pulmonary embolus (PE) at the time of recurrence compared
      with first event is unstudied. In a retrospective cohort of patients we compared
      PE size at recurrence versus the initial PE. Rates of massive PE at recurrence
      were low whether the first PE was massive or unmassive. Studies to determine PE
      size and severity at recurrence when anticoagulation is stopped are needed.
      SUMMARY: Background The size of recurrent pulmonary embolus (PE) in relation to a
      prior event could be a factor in deciding whether to continue anticoagulation.
      There are no published data on this subject to help with counselling patients.
      Objectives To determine whether size of a first PE predicts the size at
      recurrence. Patients and methods This was a retrospective cohort study of
      consecutive patients with recurrent PE over 25 months at a single tertiary
      center. In confirmed cases the sizes of first and recurrent PEs were grouped into
      radiologically non-massive PE (RNMPE) or radiologically massive PE (RMPE) if
      there was bilateral main pulmonary artery thrombus, saddle PE or right
      ventricular strain on the computerized tomography pulmonary angiogram. Results
      Sixty-three patients were included in the study (37 exclusions). Thirty-seven
      patients were men and 26 women, with a median age of 72 years; 33.3% of PEs were
      unprovoked. Patients whose first PE was an RNMPE (46/63 or 73% of patients) had a
      15.2% (95% confidence interval [CI], 7.6-28.2%) chance of RMPE at recurrence and
      a 32.6% (95% CI 20.9-47.0%) chance of having a larger PE at recurrence, whereas
      those who presented first with an RMPE (17/63 or 27% or patients) had a 17.6%
      (95% CI, 6.2-41.0%) chance of RMPE at recurrence (odds ratio, 1.19; CI, 0.27
      5.27). Conclusions Risk of a massive PE at recurrence is low (and similar)
      irrespective of the size of the first PE in this single study. Further studies
      are warranted as this could help in decisions on long-term anticoagulation.

PMID- 28430392
TI  - Depressive symptoms in older adults awaiting cataract surgery: methodological and
      statistical issues - response.

PMID- 28430393
TI  - In vivo cutaneous malignancy diagnosis using mitochondrial imaging.

PMID- 28430394
TI  - Structure-Based Design of a New Scaffold for Cell-Penetrating Peptidic Inhibitors
      of the Histone Demethylase PHF8.
AB  - The histone demethylase PHF8 catalyzes demethylation of mono- and di-methylated
      Lys9 on histone H3 (H3K9me1/2), and is a transcriptional activator involved in
      the development and cancer. Affinity and specificity of PHF8 towards H3K9me2 is
      affected by interaction with both the catalytic domain and a PHD reader domain.
      The latter specifically recognizes tri-methylated Ly4 on histone H3. A fragment
      of the histone H3 tail with tri-methylated Lys4 was used as a template for the
      structure-based design of a cyclic, cell-penetrating peptide that exhibits
      micromolar binding affinity to PHF8 in biochemical assays. The inhibitor has
      significantly lower affinity towards KDM2 enzymes (the phylogenetically closest
      subfamily), and to KDM3 and KDM6 subfamilies. Selectivity is only marginal
      towards an enzyme from the KDM4 family, which shares histone tail specificity
      with PHF8. It is a substrate of KDM5B, thus implying that the free N terminus is
      not part of the KDM5 enzyme substrate recognition machinery. The cyclic peptide's
      ability to penetrate cells is achieved by incorporation of a sequence derived
      from HIV Tat. The derived cyclic peptide can be used as a starting compound in
      the search for potent and selective PHF8 inhibitors.

PMID- 28430395
TI  - Flower colour polymorphism in the Mediterranean Basin: occurrence, maintenance
      and implications for speciation.
AB  - Flower colour polymorphism (FCP) is the occurrence of at least two discrete
      flower colour variants in the same population. Despite a vast body of research
      concerning the maintenance and evolutionary consequences of FCP, only recently
      has the spatial variation in morph frequencies among populations been explored.
      Here we summarise the biochemical and genetic basis of FCP, the factors that have
      been proposed to explain their maintenance, and the importance of FCP and its
      geographic variation in the speciation process. We also review the incidence of
      FCP in the environmentally heterogeneous Mediterranean Basin. Nearly 88% of
      Mediterranean FCP species showed anthocyanin-based polymorphisms. Concerning the
      evolutionary mechanisms that contribute to maintain FCP, selection by pollinators
      is suggested in some species, but in others, selection by non-pollinator agents,
      genetic drift or gene flow are also found; in some cases different processes
      interact in the maintenance of FCP. We emphasise the role of both autonomous
      selfing and clonal reproduction in FCP maintenance. Mediterranean polymorphic
      species show mainly monomorphic populations with only a few polymorphic ones,
      which generate clinal or mosaic patterns of variation in FCP. No cases of species
      with only polymorphic populations were found. We posit that different
      evolutionary processes maintaining polymorphism the Mediterranean Basin will
      result in a continuum of geographic patterns in morph compositions and relative
      frequencies of FCP species.

PMID- 28430396
TI  - Patient and caregiver perspectives on decision support for symptom and quality of
      life management during cancer treatment: Implications for eHealth.
AB  - OBJECTIVES: Adequate symptom and quality-of-life (SQL) management is a priority
      during cancer treatment. eHealth is a timely way to enhance patient-engagement,
      facilitate communication, and improve health outcomes. The objectives of this
      study were to describe patient and caregivers' perspectives for providing,
      processing, and managing SQL data to enhance communication and identify desired
      components for decision support. METHODS: Data were collected from 64
      participants through questionnaires and focus groups. Analysis was conducted
      using NVivo. Open and axial coding was completed, grouping commonalities and
      large constructs into nodes to identify and synthesize themes. RESULTS: Face-to
      face meetings with clinicians were the prime time to communicate, and patients
      strove to understand treatment options and the effect on SQL by bringing
      caregivers to their visits, taking notes, tracking symptoms, and creating
      portable health records. Patients/caregivers struggled to self-manage their
      symptoms and were uncertain when to contact clinicians when experiencing
      uncontrolled symptoms. Most participants identified eHealth solutions for
      decision support. However, 38% of participants (n = 24) rarely used computers and
      identified non-eHealth options for decision support. Core components for both
      eHealth and non-eHealth systems were access to (1) cancer information, (2)
      medical records, (3) peer support, and (4) improved support and understanding on
      when to contact clinicians. CONCLUSIONS: Patients were faced with an overwhelming
      amount of information and relied on their caregivers to help navigate the
      complexities of cancer care and self-manage SQL. Health technologies can provide
      informational support; however, decision support needs to span multiple venues to
      avoid increasing disparities caused by a digital divide.

PMID- 28430397
TI  - Respiratory virus detection during hospitalisation for lower respiratory tract
      infection in children under 2 years in South Auckland, New Zealand.
AB  - AIM: To describe respiratory virus detection in children under 2 years of age in
      a population admitted with lower respiratory infection and to assess correlation
      with measures of severity. METHODS: Nasopharyngeal aspirates from infants
      admitted with lower respiratory tract infection (n = 1645) over a 3-year time
      period were tested by polymerase chain reaction. We collected epidemiological and
      clinical data on all children. We assessed the correlation of presence of virus
      with length of hospital stay, intensive care admission and consolidation on chest
      X-ray. RESULTS: Of the children admitted 34% were Maori, 43% Pacific and 75%
      lived in areas in the bottom quintile for socio-economic deprivation. A virus was
      found in 94% of those tested including 30% with multiple viruses. Picornavirus
      was present in 59% including 34% as the sole virus. Respiratory syncytial virus
      was found in 39%. Virus co-detection was not associated with length of stay,
      chest X-ray changes or intensive care unit admission. CONCLUSION: In this
      disadvantaged predominately Maori and Pacific population, picornavirus is
      commonly found as a sole virus, respiratory syncytial virus is frequent but
      immunisation preventable influenza is infrequent. We did not find that co
      detection of viruses was linked to severity.

PMID- 28430398
TI  - Impact of Acid-Reducing Agents on the Pharmacokinetics of Palbociclib, a Weak
      Base With pH-Dependent Solubility, With Different Food Intake Conditions.
AB  - Palbociclib free base capsule is a weak base drug with highly pH-dependent
      solubility. In vitro and in vivo studies evaluated the impact of acid-reducing
      agents on exposure of palbociclib and determined whether the impact, if any, can
      be mitigated by food. A drug-drug interaction study (study 1) was conducted first
      under fasted conditions and showed that coadministration of multiple doses of the
      proton-pump inhibitor rabeprazole substantially reduced palbociclib mean area
      under the concentration-time curve from time 0 to infinity and maximum observed
      plasma concentration by 62% and 80%, respectively. In vitro assessment suggested
      that the presence of bile salt mixed micelles to mimic the fed state can
      significantly enhance the solubility of palbociclib. Subsequently, study 2 was
      conducted under fed conditions and demonstrated that coadministration of
      rabeprazole decreased palbociclib maximum observed plasma concentration by 41%
      but had limited impact on area under the concentration-time curve from 0 to
      infinity (13% decrease). This study also showed that the histamine-2 receptor
      antagonist famotidine and local antacid with staggered dosing had no impact on
      palbociclib exposure under fed conditions. Food intake effectively mitigated the
      impact of acid-reducing agents on palbociclib exposure. Palbociclib free base
      capsule should be taken with food, and acid-reducing agent use does not need to
      be avoided.

PMID- 28430399
TI  - Targeting Conformational Activation of CDK2 Kinase.
AB  - Cyclin-dependent kinases constitute attractive pharmacological targets for cancer
      therapeutics, yet inhibitors in clinical trials target the ATP-binding pocket of
      the CDK and therefore suffer from limited selectivity and emergence of
      resistance. The more recent development of allosteric inhibitors targeting
      conformational plasticity of protein kinases offers promising perspectives for
      therapeutics. In particular tampering with T-loop dynamics of CDK2 kinase would
      provide a selective means of inhibiting this kinase, by preventing its
      conformational activation. To this aim we engineered a fluorescent biosensor that
      specifically reports on conformational changes of CDK2 activation loop and is
      insensitive to ATP or ATP-competitive inhibitors, which constitutes a highly
      sensitive probe for identification of selective T-loop modulators. This biosensor
      was successfully applied to screen a library of small chemical compounds leading
      to discovery of a family of quinacridine analogs, which potently inhibit cancer
      cell proliferation, and promote accumulation of cells in S phase and G2. These
      compounds bind CDK2/ Cyclin A, inhibit its kinase activity, compete with
      substrate binding, but not with ATP, and dock onto the T-loop of CDK2. The best
      compound also binds CDK4 and CDK4/Cyclin D1, but not CDK1. The strategy we
      describe opens new doors for the discovery of a new class of allosteric CDK
      inhibitors for cancer therapeutics.

PMID- 28430400
TI  - Highly sensitive HPLC method for the determination of galantamine in human plasma
      and urine through derivatization with dansyl chloride using fluorescence
      detector.
AB  - A new method based on fluorescence derivatization with 5-(dimethylamino)
      naphthalene-1-sulfonyl chloride (dansyl chloride) was developed for the
      quantitative determination of galantamine in human plasma and urine using high
      performance liquid chromatography. The reaction between galantamine and dansyl
      chloride was optimally realized in 30 min at room temperature and pH 10.5, with a
      reagent to galantamine molar ratio of 2.13. The derivative was extracted with
      dichloromethane, and the extract was dried under a nitrogen stream and dissolved
      in the mobile phase. Chromatographic analysis was performed with an Inertsil C18
      column and a mobile phase comprising 40% acetonitrile and 60% 10 mM o-phosphoric
      acid, 1.2 ml/min. The injection volume was 20 MUl. The derivatives were detected
      with a fluorescence detector (excitation 375 nm/emission 537 nm). The retention
      time for the dansyl derivative of galantamine was 16.8 min. Linearity was
      observed between 125 and 2000 ng/ml in water, urine and plasma. The limit of
      detection and limit of quantification for the developed method were 6.27-70.99
      and 18.81-212.97 ng/ml, respectively. Per cent recovery was calculated as 95.15
      for urine and 95.78 for plasma. Interday repeatability values for urine and
      plasma samples (n = 6) at three different concentrations were calculated as a per
      cent relative standard deviation of 0.24-0.59 and 0.35-0.56. The corresponding
      per cent relative standard deviation values for intraday repeatability were 0.13
      0.51 and 0.04-0.15, respectively.

PMID- 28430401
TI  - Professor Crispian Scully.

PMID- 28430403
TI  - Congenital polypoid cutaneous adnexal and mesenchymal hamartoma: an
      underdiagnosed entity - Report of two cases.

PMID- 28430402
TI  - A removable virus vector suitable for plant genome editing.
AB  - Plant genome editing is achieved by the expression of sequence-specific nucleases
      (SSNs). RNA virus vector-mediated expression of SSNs is a promising approach for
      transgene integration-free targeted mutagenesis in plants. However, the removal
      of virus vectors from infected plants is challenging because no antiviral drugs
      are available against plant viruses. Here, we developed a removable RNA virus
      vector that carries the target site of tobacco microRNA398 (miR398) whose
      expression is induced during shoot regeneration. In the inoculated leaves in
      which expression of miR398 is not induced, insertion of the miR398 target site
      did not affect the practicability of the virus vector. When shoots were
      regenerated from the infected leaves, miR398 was expressed and viral RNA was
      eliminated. The virus vector successfully expressed SSNs in inoculated leaves,
      from which virus-free genome-edited plants were regenerated via tissue culture.

PMID- 28430404
TI  - Understanding asexual identity as a means to facilitate culturally competent
      care: A systematic literature review.
AB  - AIMS AND OBJECTIVES: To provide a contemporary overview of asexuality and the
      implications this has for healthcare practice. BACKGROUND: Individuals belonging
      to sexual minority groups face many barriers in accessing appropriate health
      care. The term "sexual minority group" is usually used to refer to lesbian women,
      gay, bisexual and transgender individuals. Anecdotal and research evidence
      suggests that those who identify as asexual have similar poor experiences.
      DESIGN: Systematic review and qualitative analysis. METHODS: This work uses a
      systematic review and qualitative analysis of the existing interview data from
      self-identified asexuals, to construct features of the asexual identity. The
      findings will help practitioners and health professionals develop an
      understanding of this poorly understood construct. Ultimately this work is aimed
      at facilitating culturally competent care in the context of asexuality. RESULTS:
      Qualitative analysis produced three themes, which can be used, not only to frame
      asexuality in a positive and normalising way, but also to provide greater
      understanding of asexuality, "romantic differences coupled with sexual
      indifference," "validation through engagement with asexual communities" and "a
      diversity of subasexual identities." CONCLUSIONS: Having some understanding of
      what it means to identify as asexual, and respecting the choices made by asexuals
      can markedly improve the experiences of those who embrace an asexual identity
      when engaging with health care. RELEVANCE TO CLINICAL PRACTICE: Anecdotal
      evidence, taken from one of the largest asexual online forums, suggests that a
      number of self-identified asexuals choose not to disclose their identity to
      healthcare professionals through fear of their asexual status being pathologised,
      problematised or judged. Given that asexuality is a poorly understood concept,
      this may be due to lack of understanding on behalf of healthcare providers. The
      review provides health professionals and practitioners working in clinical
      settings with some insights of the features of an asexual identity to facilitate
      culturally competent care.

PMID- 28430405
TI  - When to Refer to Palliative Care: Part Two.

PMID- 28430406
TI  - Haiti Earthquake Trauma: How to Cope With the Inhumane Humanity.

PMID- 28430407
TI  - Three-Dimensional Arylene Diimide Frameworks for Highly Stable Lithium Ion
      Batteries.
AB  - Lithium ion batteries are the best commercial technology to satisfy the energy
      storage needs of current and emerging applications. However, the use of
      transition-metal-based cathodes precludes them from being low-cost, sustainable,
      and environmentally benign, even with recycling programs in place. In this study,
      we report a highly stable organic material that can be used in place of the
      transition-metal cathodes. By creating a three-dimensional framework based on
      triptycene and perylene diimide (PDI), a cathode can be constructed that
      mitigates stability issues that organic electrodes typically suffer from. When a
      lithium ion battery is assembled using the PDI-triptycene framework (PDI-Tc)
      cathode, a capacity of 75.9 mAh g-1 (78.7% of the theoretical value) is obtained.
      Importantly, the battery retains a near perfect Coulombic efficiency and >80% of
      its capacity after cycling 500 times, which is the best value reported to date
      for PDI-based materials.

PMID- 28430408
TI  - Amplifying Riboswitch Signal Output Using Cellular Wiring.
AB  - If fieldable riboswitch-based biological sensors are to fulfill their potential,
      it is necessary to increase their signal output. Here we report a novel modular
      amplification system using a riboswitch to initiate signaling between a sensing
      strain and a reporter strain of E. coli. A quorum sensing signaling molecule
      biologically wires the sensing and reporter strains together. The amplification
      circuit increased the amount of fluorescence generated on ligand binding compared
      to when the riboswitch controlled fluorescence expression directly. This had the
      corollary effect of increasing the sensitivity of the system, and allowed
      riboswitch-based reporting in E. coli strains that did not produce a detectable
      output when the riboswitch directly controlled reporter expression. The
      amplification circuit also reduced the time required to detect a signal output.
      The modularity of this amplification system coupled with the achievable increases
      in output can advance the development of riboswitches and biological sensors.

PMID- 28430409
TI  - Chiral Metal-Oxide Nanofilms by Cellulose Template Using Atomic Layer Deposition
      Process.
AB  - In this article, we describe an advance approach for the fabrication of chiral
      metal-oxide nanofilms. Our approach is based on the atomic layer deposition of
      titania and alumina nanofilms onto cellulose microfibers, used as chiral
      templates, leading to the formation of chiral nanofilms with a spatial fibrous
      structure. The chiral nanofilms were extensively characterized by X-ray
      photoelectron spectroscopy and high-resolution electron microscopy. The chiral
      property of the produced titania nanofilms was studied by enantioselective
      adsorption experiments using circular-dichroism spectroscopy and chiral high
      performance liquid chromatography. We demonstrate the application of the titania
      chiral nanofilms for enantioselective crystallization. Overall, the basic
      principle for the preparation of chiral nanofilms by atomic layer deposition is
      demonstrated, as well as their uses for several enantioselective applications.

PMID- 28430410
TI  - Modeling and Simulation of Piezoelectrically Driven Self-Charging Lithium Ion
      Batteries.
AB  - Self-charging lithium ion batteries (SCLIBs) that hybridize mechanical energy
      harvesting and storage processes into one process can be fabricated using a
      piezoelectric polyvinylidene fluoride (PVDF) film as a separator in lithium ion
      batteries. In this paper, the deintercalation reaction at LiCoO2 and
      intercalation reaction at graphite were studied under an internal piezoelectric
      field using density functional theory. It was found that the internal
      piezoelectric field applied on the anode can increase intercalation energies and
      diffusion behavior, at the same time, and the internal piezoelectric field
      facilitates the deintercalation reaction at the cathode. The simulation results
      revealed the self-charging mechanism of SCLIBs, in which the piezoelectric
      potential can assist the deintercalation and intercalation proccesses at the
      cathode and anode upon self-charging, which may be responsible for the
      experimentally observed efficiency of SCLIBs.

PMID- 28430411
TI  - 2-Methylimidazole-Derived Ni-Co Layered Double Hydroxide Nanosheets as High Rate
      Capability and High Energy Density Storage Material in Hybrid Supercapacitors.
AB  - A new method based on one-step solvothermal reaction is demonstrated to
      synthesize ultrathin Ni-Co layered double hydroxide (LDH) nanosheets, which grow
      directly on a flexible carbon fiber cloth (NiCo-LDH/CFC). Through using 2
      methylimidazole as complex and methanol as solvent, the as-prepared NiCo-LDH/CFC
      shows a (003) facet preferential growth and an expanded interlayer spacing
      structure, resulting in a unique 3D porous nanostructure with a thickness of
      nanosheets of around 5-7 nm that shows high energy storage performance. By
      controlling the ratio of Ni/Co = 4:1 in the precursor solution, the electrode
      shows a specific capacitance of 2762.7 F g-1 (1243.2 C g-1) at a current density
      of 1 A g-1. Nevertheless, the optimal composition is obtained with Ni/Co = 1:1,
      which produces a specific capacitance of 2242.9 F g-1 (1009.3 C g-1) at 1 A g-1
      and shows an excellent rate capability with 61% of the original capacitance being
      retained at a current density of 60 A g-1. The hybrid supercapacitor (HSC) based
      on the NiCo-LDH/CFC exhibits a maximum energy density of 59.2 Wh kg-1 and power
      densities of 34 kW kg-1, respectively. Long-term stability test shows that 82% of
      the original capacitance of the HSC remains after 5000 cycles. Importantly, the
      electrochemical performance of the solid-state flexible supercapacitors based on
      the prepared NiCo-LDH/CFC electrode showed a negligible change when the device
      was bent up to 180 degrees . The performance of synthesized NiCo-LDH/CFC
      indicates the great potential of the material for delivering both high energy
      density and high power density in energy storage devices.

PMID- 28430412
TI  - Quasi-Two-Dimensional Metal Oxide Semiconductors Based Ultrasensitive
      Potentiometric Biosensors.
AB  - Ultrasensitive field-effect transistor-based biosensors using quasi-two
      dimensional metal oxide semiconductors were demonstrated. Quasi-two-dimensional
      low-dimensional metal oxide semiconductors were highly sensitive to electrical
      perturbations at the semiconductor-bio interface and showed competitive
      sensitivity compared with other nanomaterial-based biosensors. Also, the solution
      process made our platform simple and highly reproducible, which was favorable
      compared with other nanobioelectronics. A quasi-two-dimensional In2O3-based pH
      sensor showed a small detection limit of 0.0005 pH and detected the glucose
      concentration at femtomolar levels. Detailed electrical characterization unveiled
      how the device's parameters affect the biosensor sensitivity, and lowest
      detectable charge was extrapolated, which was consistent with the experimental
      data.

PMID- 28430413
TI  - Bioimaging with Macromolecular Probes Incorporating Multiple BODIPY Fluorophores.
AB  - Seven macromolecular constructs incorporating multiple borondipyrromethene
      (BODIPY) fluorophores along a common poly(methacrylate) backbone with decyl and
      oligo(ethylene glycol) side chains were synthesized. The hydrophilic
      oligo(ethylene glycol) components impose solubility in aqueous environment on the
      overall assembly. The hydrophobic decyl chains effectively insulate the
      fluorophores from each other to prevent detrimental interchromophoric
      interactions and preserve their photophysical properties. As a result, the
      brightness of these multicomponent assemblies is approximately three times
      greater than that of a model BODIPY monomer. Such a high brightness level is
      maintained even after injection of the macromolecular probes in living nematodes,
      allowing their visualization with a significant improvement in signal-to-noise
      ratio, relative to the model monomer, and no cytotoxic or behavioral effects. The
      covalent scaffold of these macromolecular constructs also permits their
      subsequent conjugation to secondary antibodies. The covalent attachment of
      polymer and biomolecule does not hinder the targeting ability of the latter and
      the resulting bioconjugates can be exploited to stain the tubulin structure of
      model cells to enable their visualization with optimal signal-to-noise ratios.
      These results demonstrate that this particular structural design for the
      incorporation of multiple chromophores within the same covalent construct is a
      viable one to preserve the photophysical properties of the emissive species and
      enable the assembly of bioimaging probes with enhanced brightness.

PMID- 28430414
TI  - Dynamic and Energetic Signatures of Adenine Tracts in a rA-dT RNA-DNA Hybrid and
      in Homologous RNA-DNA, RNA-RNA, and DNA-DNA Double Helices.
AB  - Nuclear magnetic resonance spectroscopy and proton exchange are being used to
      characterize the opening reactions of individual base pairs in the RNA-DNA hybrid
      5'-rGCGAUAAAAAGGCC-3'/5'-dGGCCTTTTTATCGC-3'. The hybrid contains a central tract
      of five rA-dT base pairs. The rates and the equilibrium constant of the opening
      reaction for each base pair are determined from the dependence of the exchange
      rates of imino protons on ammonia concentration, at 10  degrees C. The results
      are compared to those previously obtained by our laboratory for three homologous
      duplexes of the same base sequence (except for the appropriate T/U substitution),
      containing tracts of dA-rU, rA-rU, or dA-dT base pairs. The rA-dT tract is
      distinguished by an enhanced propensity of the base pairs to exist in the
      extrahelical state. The opening rates of rA-dT base pairs also exhibit a strong
      dependence on the location of the base pair in the structure; namely, as one
      advances into the tract, the opening rates of rA-dT base pairs gradually
      decrease. The local stability of each rA-dT base pair within the tract is the
      same as that of the corresponding rA-rU base pair in the homologous RNA-only
      duplex but differs from the stabilities of dA-dT and dA-rU base pairs in the
      other two duplexes (namely, dA-dT > rA-dT > dA-rU). These results demonstrate
      that, in nucleic acid double helices with the same base sequence, the opening
      dynamics and the energetics of individual base pairs are strongly influenced by
      the nature of the strand and by the structural context of the base pair.

PMID- 28430415
TI  - Omnidirectional Harvesting of Weak Light Using a Graphene Quantum Dot-Modified
      Organic/Silicon Hybrid Device.
AB  - Despite great improvements in traditional inorganic photodetectors and
      photovoltaics, more progress is needed in the detection/collection of light at
      low-level conditions. Traditional photodetectors tend to suffer from high noise
      when operated at room temperature; therefore, these devices require additional
      cooling systems to detect weak or dim light. Conventional solar cells also face
      the challenge of poor light-harvesting capabilities in hazy or cloudy weather.
      The real world features such varying levels of light, which makes it important to
      develop strategies that allow optical devices to function when conditions are
      less than optimal. In this work, we report an organic/inorganic hybrid device
      that consists of graphene quantum dot-modified poly(3,4-ethylenedioxythiophene)
      polystyrenesulfonate spin-coated on Si for the detection/harvest of weak light.
      The hybrid configuration provides the device with high responsivity and
      detectability, omnidirectional light trapping, and fast operation speed. To
      demonstrate the potential of this hybrid device in real world applications, we
      measured near-infrared light scattered through human tissue to demonstrate
      noninvasive oximetric photodetection as well as characterized the device's
      photovoltaic properties in outdoor (i.e., weather-dependent) and indoor weak
      light conditions. This organic/inorganic device configuration demonstrates a
      promising strategy for developing future high-performance low-light compatible
      photodetectors and photovoltaics.

PMID- 28430416
TI  - Complementary Benzophenone Cross-Linking/Mass Spectrometry Photochemistry.
AB  - Use of a heterobifunctional photoactivatable cross-linker, sulfo-SDA (diazirine),
      has yielded high-density data that facilitated structure modeling of individual
      proteins. We expand the photoactivatable chemistry toolbox here with a second
      reagent, sulfo-SBP (benzophenone). This further increases the density of photo
      cross-linking to a factor of 20* over conventional cross-linking. Importantly,
      the two different photoactivatable groups display orthogonal directionality,
      enabling access to different protein regions, unreachable with a single cross
      linker.

PMID- 28430417
TI  - Charge Separation Mechanisms in Ordered Films of Self-Assembled Donor-Acceptor
      Dyad Ribbons.
AB  - Orthogonal attachment of polar and nonpolar side-chains to a zinc porphyrin
      perylenediimide dyad (ZnP-PDI, 1a) is shown to result in self-assembly of ordered
      supramolecular ribbons in which the ZnP and PDI molecules form segregated pi
      stacked columns. Following photoexcitation of the ordered ribbons, ZnP+*-PDI-*
      radical ion pairs form in <200 fs and subsequently produce a 30 +/- 3% yield of
      free charge carriers that live for about 100 MUs. Elongating the side chains on
      ZnP and PDI in 1b enhances the order of the films, but does not result in an
      increase in free charge carrier yield. In addition, this yield is independent of
      temperature, free energy of reaction, and the ZnP-PDI distance in the covalent
      dyad. These results suggest that the free charge carrier yield in this system is
      not limited by a bound charge transfer (CT) state or promoted by a vibronically
      hot CT state. Instead, it is likely that pi-stacking of the segregated donors and
      acceptors within the ribbons results in delocalization of the charges following
      photoexcitation, allowing them to overcome Coulombic attraction and generate free
      charge carriers.

PMID- 28430418
TI  - Effects of Small Polar Molecules (MA+ and H2O) on Degradation Processes of
      Perovskite Solar Cells.
AB  - Degradation mechanisms of methylammonium lead halide perovskite solar cells
      (PSCs) have drawn much attention recently. Herein, the bulk and surface
      degradation processes of the perovskite were differentiated for the first time by
      employing combinational studies using electrochemical impedance spectroscopy
      (EIS), capacitance frequency (CF), and X-ray diffraction (XRD) studies with
      particular attention on the roles of small polar molecules (MA+ and H2O). CF
      study shows that short-circuit current density of the PSCs is increased by H2O at
      the beginning of the degradation process coupled with an increased surface
      capacitance. On the basis of EIS and XRD analysis, we show that the bulk
      degradation of PSCs involves a lattice expansion process, which facilitates MA+
      ion diffusion by creating more efficient channels. These results provide a better
      understanding of the roles of small polar molecules on degradation processes in
      the bulk and on the surface of the perovskite film.

PMID- 28430419
TI  - Prediction of Hydrolysis Products of Organic Chemicals under Environmental pH
      Conditions.
AB  - Cheminformatics-based software tools can predict the molecular structure of
      transformation products using a library of transformation reaction schemes. This
      paper presents the development of such a library for abiotic hydrolysis of
      organic chemicals under environmentally relevant conditions. The hydrolysis
      reaction schemes in the library encode the process science gathered from peer
      reviewed literature and regulatory reports. Each scheme has been ranked on a
      scale of one to six based on the median half-life in a data set compiled from
      literature-reported hydrolysis rates. These ranks are used to predict the most
      likely transformation route when more than one structural fragment susceptible to
      hydrolysis is present in a molecule of interest. Separate rank assignments are
      established for pH 5, 7, and 9 to represent standard conditions in hydrolysis
      studies required for registration of pesticides in Organisation for Economic Co
      operation and Development (OECD) member countries. The library is applied to
      predict the likely hydrolytic transformation products for two lists of chemicals,
      one representative of chemicals used in commerce and the other specific to
      pesticides, to evaluate which hydrolysis reaction pathways are most likely to be
      relevant for organic chemicals found in the natural environment.

PMID- 28430420
TI  - A Thorium Chalcogenolate Series Generated by Atom Insertion into Thorium-Carbon
      Bonds.
AB  - A new thorium monoalkyl complex, Th(CH2SiMe3)(L3) (L = MeC(NiPr)2) (2), undergoes
      insertion of chalcogen atoms resulting in a series of thorium chalcogenolate
      complexes, Th(ECH2SiMe3)(L3) (E = S, SS, Se, Te; 5-8). Complex 6 represents the
      first alkyl disulfide thorium species and illustrates the ability of 2 to undergo
      controllable, stoichiometric atom insertion. All complexes have been
      characterized by 1H and 13C NMR spectroscopy, FTIR, EA, and melting point, and in
      the case of 1, 2, and 4-8, X-ray crystallography. Insertion was achieved by
      balancing the thermodynamic driving force of chalcogenolate formation versus the
      BDE of the pnictogen-chalcogen bond in the transfer reagent. Utilizing Me3NO as
      an oxygen atom transfer reagent led to C-H activation and SiMe4 extrusion rather
      than oxygen atom insertion, resulting in the alkoxide complex Th(OCH2NMe2)(L3)
      (4).

PMID- 28430421
TI  - Flexibility of the Carbodiphosphorane, (Ph3P)2C: Structural Characterization of a
      Linear Form.
AB  - X-ray diffraction studies demonstrate that crystals of the carbodiphosphorane,
      (Ph3P)2C, obtained from solutions in benzene, exhibit a linear P-C-P interaction.
      This observation is in contrast to the highly bent structures that have been
      previously reported for this molecule, thereby providing experimental evidence
      that the coordination geometry at zerovalent carbon may be very flexible. Density
      functional theory calculations support the experimental observations by
      demonstrating that the energy of (Ph3P)2C varies relatively little over the range
      130-180 degrees .

PMID- 28430422
TI  - Gauging Donor/Acceptor Properties and Redox Stability of Chelating Click-Derived
      Triazoles and Triazolylidenes: A Case Study with Rhenium(I) Complexes.
AB  - Bidentate ligands containing at least one triazole or triazolylidene (mesoionic
      carbene, MIC) unit are extremely popular in contemporary chemistry. One reason
      for their popularity is the similarities as well as differences in the
      donor/acceptor properties that these ligands display in comparison to their
      pyridine or other N-heterocyclic carbene counterparts. We present here seven
      rhenium(I) carbonyl complexes where the bidentate ligands contain combinations of
      pyridine/triazole/triazolylidene. These are the first examples of rhenium(I)
      complexes with bidentate 1,2,3-triazol-5-ylidene-containing ligands. All
      complexes were structurally characterized through 1H and 13C NMR spectroscopy as
      well as through single-crystal X-ray diffraction. A combination of structural
      data, redox potentials from cyclic voltammetry, and IR data related to the CO
      coligands are used to gauge the donor/acceptor properties of these chelating
      ligands. Additionally, a combination of UV-vis-near-IR/IR/electron paramagnetic
      resonance spectroelectrochemistry and density functional theory calculations are
      used to address questions related to the electronic structures of the complexes
      in various redox states, their redox stability, and the understanding of chemical
      reactivity following electron transfer in these systems. The results show that
      donor/acceptor properties in these bidentate ligands are sometimes, but not
      always, additive with respect to the individual components. Additionally, these
      results point to the fact that MIC-containing ligands confer remarkable redox
      stability to their fac-Re(CO)3-containing metal complexes. These findings will
      probably be useful for fields such as homogeneous- and electro-catalysis,
      photochemistry, and electrochemistry, where fac-Re(CO)3 complexes of
      triazoles/triazolylidenes are likely to find use.

PMID- 28430423
TI  - Hafnium-Based Contrast Agents for X-ray Computed Tomography.
AB  - Heavy-metal-based contrast agents (CAs) offer enhanced X-ray absorption for X-ray
      computed tomography (CT) compared to the currently used iodinated CAs. We report
      the discovery of new lanthanide and hafnium azainositol complexes and their
      optimization with respect to high water solubility and stability. Our efforts
      culminated in the synthesis of BAY-576, an uncharged hafnium complex with 3:2
      stoichiometry and broken complex symmetry. The superior properties of this
      asymmetrically substituted hafnium CA were demonstrated by a CT angiography study
      in rabbits that revealed excellent signal contrast enhancement.

PMID- 28430424
TI  - Elucidation of the Stereospecificity of C-Methyltransferases from trans-AT
      Polyketide Synthases.
AB  - S-Adenosyl methionine (SAM)-dependent C-methyltransferases are responsible for
      the C2-methylation of 3-ketoacyl-acyl carrier protein (ACP) intermediates to give
      the corresponding 2-methy-3-ketoacyl-ACP products during bacterial polyketide
      biosynthesis mediated by trans-AT polyketide synthases that lack integrated acyl
      transferase (AT) domains. A coupled ketoreductase (KR) assay was used to assign
      the stereochemistry of the C-methyltransferase-catalyzed reaction. Samples of
      chemoenzymatically generated 3-ketopentanoyl-ACP (9) were incubated with SAM and
      BonMT2 from module 2 of the bongkrekic acid polyketide synthase. The resulting 2
      methyl-3-ketopentanoyl-ACP (10) was incubated separately with five (2R)- or (2S)
      methyl specific KR domains. Analysis of the derived 2-methyl-3-hydroxypentanoate
      methyl esters (8) by chiral GC-MS established that the BonMT2-catalyzed
      methylation generated exclusively (2R)-2-methyl-3-ketopentanoyl-ACP ((2R)-10).
      Identical results were also obtained with three additional C-methyltransferases
      BaeMT9, DifMT1, and MupMT1-from the bacillaene, difficidin, and mupirocin trans
      AT polyketide synthases.

PMID- 28430425
TI  - Environmental Growth of Enterococci and Escherichia coli in Feedlot Catch Basins
      and a Constructed Wetland in the Absence of Fecal Input.
AB  - Population structures of fecal indicator bacteria (FIB) isolated from catch
      basins, a constructed wetland, and feces from a beef cattle feedlot were compared
      over a two-year period. Enterococcus hirae accounted for 92% of the fecal
      isolates, whereas secondary environments were characterized by greater relative
      abundance of environmentally adapted species including Enterococcus
      casseliflavus. While enterococci densities in the catch basins and wetland were
      similar under wet and drought conditions, E. hirae predominated during rainy
      periods, while E. casseliflavus predominated during drought conditions.
      Environmentally adapted species accounted for almost half of the erythromycin
      resistant enterococci isolated from the wetland. Densities of Escherichia coli
      were also comparable during wet versus drought conditions, and the relative
      abundance of strains from environmentally adapted clades was greater in secondary
      environments compared to feces. Unlike enterococci, fewer environmentally adapted
      E. coli strains were isolated on selective media containing ceftriaxone from the
      wetland compared to feces, suggesting resistance to this antibiotic may not be
      well maintained in the absence of selective pressure. Overall, these findings
      suggest that secondary environments select for environmentally adapted FIB. While
      these species and clades tend to be of limited clinical relevance, they could
      potentially serve as reservoirs of antimicrobial resistance.

PMID- 28430427
TI  - Performance of the AMOEBA Water Model in the Vicinity of QM Solutes: A Diagnosis
      Using Energy Decomposition Analysis.
AB  - The importance of incorporating solvent polarization effects into the modeling of
      solvation processes has been well-recognized, and therefore a new generation of
      hybrid quantum mechanics/molecular mechanics (QM/MM) approaches that accounts for
      this effect is desirable. We present a fully self-consistent, mutually
      polarizable QM/MM scheme using the AMOEBA force field, in which the total energy
      of the system is variationally minimized with respect to both the QM electronic
      density and the MM induced dipoles. This QM/AMOEBA model is implemented through
      the Q-Chem/LibEFP code interface and then applied to the evaluation of solute
      solvent interaction energies for various systems ranging from the water dimer to
      neutral and ionic solutes (NH3, NH4+, CN-) surrounded by increasing numbers of
      water molecules (up to 100). In order to analyze the resulting interaction
      energies, we also utilize an energy decomposition analysis (EDA) scheme which
      identifies contributions from permanent electrostatics, polarization, and van der
      Waals (vdW) interaction for the interaction between the QM solute and the solvent
      molecules described by AMOEBA. This facilitates a component-wise comparison
      against full QM calculations where the corresponding energy components are
      obtained via a modified version of the absolutely localized molecular orbitals
      (ALMO)-EDA. The results show that the present QM/AMOEBA model can yield
      reasonable solute-solvent interaction energies for neutral and cationic species,
      while further scrutiny reveals that this accuracy highly relies on the delicate
      balance between insufficiently favorable permanent electrostatics and softened
      vdW interaction. For anionic solutes where the charge penetration effect becomes
      more pronounced, the QM/MM interface turns out to be unbalanced. These results
      are consistent with and further elucidate our findings in a previous study using
      a slightly different QM/AMOEBA model ( Dziedzic et al. J. Chem. Phys. 2016 , 145
      , 124106 ). The implications of these results for further refinement of this
      model are also discussed.

PMID- 28430428
TI  - Full-Potential Simulation of X-ray Raman Scattering Spectroscopy.
AB  - We present a new ab initio way to calculate X-ray Raman scattering spectra within
      the independent electron approximation. Our approach avoids any approximation
      about the shape of the used potential and leads to good agreement between
      experiment and theory. We show that the momentum transfer dependence in two
      typical cases, the F K-edge in LiF and the B and N K-edges in hexagonal BN, is
      well-reproduced. A more in-depth analysis of the electronic states and of the
      local atomic structure around the absorbing atoms is at hand.

PMID- 28430429
TI  - Potential Glucocorticoid and Mineralocorticoid Effects of Nine Organophosphate
      Flame Retardants.
AB  - Organophosphate flame retardants (OPFRs), as alternatives of polybrominated
      diphenyl ethers (PBDEs), have been frequently detected in the environment and
      biota, and could pose adverse effects on organisms. However, information on the
      potential endocrine disruption of OPFRs, especially their effects on steroid
      hormone receptors, such as glucocorticoid and mineralocorticoid receptors
      (GR/MR), is limited. In this study, the dual-luciferase reporter gene assay via
      GR/MR and a H295R steroidogenesis assay were employed to evaluate the endocrine
      disruption of nine OPFRs. We found TMPP, TPHP, and TDBPP exhibited both GR and MR
      antagonistic activities, while TNBP and TDCIPP only showed MR antagonistic
      property within a concentration range of 10-8 to 10-5 mol/L(M). In the H295R
      steroidogenesis assay, the fold changes of eight steroidogenic genes in response
      to OPFRs were further studied. We found CYP17,CYP21, and CYP11B1 expression were
      significantly down-regulated following TMPP, TPHP, or TDBPP exposure at a
      concentration of 2 * 10-6 M. Meanwhile TMPP decreased the production of cortisol
      and TDBPP down-regulated the secretion of aldosterone. Our results indicate that
      some OPFRs can interact with GR and MR, and have the potential to disturb
      steroidogenesis. Data provided here will be helpful to comprehensively understand
      the potential endocrine disruption of OPFRs.

PMID- 28430426
TI  - The Rosetta All-Atom Energy Function for Macromolecular Modeling and Design.
AB  - Over the past decade, the Rosetta biomolecular modeling suite has informed
      diverse biological questions and engineering challenges ranging from
      interpretation of low-resolution structural data to design of nanomaterials,
      protein therapeutics, and vaccines. Central to Rosetta's success is the energy
      function: a model parametrized from small-molecule and X-ray crystal structure
      data used to approximate the energy associated with each biomolecule
      conformation. This paper describes the mathematical models and physical concepts
      that underlie the latest Rosetta energy function, called the Rosetta Energy
      Function 2015 (REF15). Applying these concepts, we explain how to use Rosetta
      energies to identify and analyze the features of biomolecular models. Finally, we
      discuss the latest advances in the energy function that extend its capabilities
      from soluble proteins to also include membrane proteins, peptides containing
      noncanonical amino acids, small molecules, carbohydrates, nucleic acids, and
      other macromolecules.

PMID- 28430430
TI  - Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives
      as General Anesthetics.
AB  - A novel series of optically active 2,6-disubstituted alkylphenols with improved
      anesthetic profiles compared to widely used propofol were synthesized. The
      incorporation of the cyclopropyl group not only increased the steric effect but
      also introduced stereoselective effects over their anesthetic properties.
      Compounds 1, 2, and 6 were selected as potential candidates for further
      preclinical development including studies of their water-soluble prodrugs.
      Clinical studies of candidate compound 6 (Haisco HSK3486) as a general anesthetic
      are being performed in Australia and China.

PMID- 28430431
TI  - Design, Synthesis, and Evaluation of a Series of Novel Benzocyclobutene
      Derivatives as General Anesthetics.
AB  - In the present work, a series of structurally novel benzocyclobutene derivatives
      were identified as general anesthetics through the loss of righting reflex (LORR)
      experiment on mice. Our initial efforts found compound 1a with a fused four
      membered ring on the 2,3-position of the phenol ring could significantly improve
      the safety profile. Further SAR study revealed that small hydrogen bond acceptor
      (HBA) groups are optimal for good ED50 along with much broader therapeutic
      windows, such as compounds 16b and 17. Present work demonstrates the superiority
      of this novel benzocyclobutene scaffold.

PMID- 28430432
TI  - Absolute Binding Free Energies between T4 Lysozyme and 141 Small Molecules:
      Calculations Based on Multiple Rigid Receptor Configurations.
AB  - We demonstrate the feasibility of estimating protein-ligand binding free energies
      using multiple rigid receptor configurations. On the basis of T4 lysozyme
      snapshots extracted from six alchemical binding free energy calculations with a
      flexible receptor, binding free energies were estimated for a total of 141
      ligands. For 24 ligands, the calculations reproduced flexible-receptor estimates
      with a correlation coefficient of 0.90 and a root-mean-square error of 1.59
      kcal/mol. The accuracy of calculations based on Poisson-Boltzmann/surface area
      implicit solvent was comparable to that of previously reported free energy
      calculations.

PMID- 28430434
TI  - Edible "Oleocolloids": The Final Frontier in Food Innovation?

PMID- 28430433
TI  - (2R,3S,2"R,3"R)-Manniflavanone Protects Proliferating Skeletal Muscle Cells
      against Oxidative Stress and Stimulates Myotube Formation.
AB  - We investigated the antioxidative properties of (2R,3S,2"R,3"R)-manniflavanone
      (MF) using in vitro assays and examined its effects on myogenesis and lactate
      induced oxidative stress in C2C12 cells. MF was purified from Garcinia buchananii
      stem bark. H2O2 and oxygen radical absorbance capacity assays demonstrated that
      MF is a powerful antioxidant. This finding was supported by
      diphenylpicrylhydrazine radical scavenging activity of MF. MF was less cytotoxic
      to C2C12 cells compared to ascorbic acid and myricetin. Moreover, MF accelerated
      myotube formation in the differentiated C2C12 cells by up-regulating myogenic
      proteins such as MyoG and myosin heavy chain. Furthermore, MF rescued late
      differentiation of myoblast suppressed by lactate treatment and up-regulated the
      expression levels of Nrf2 in lactate-induced oxidative stress, indicating that MF
      stimulates antioxidative activity inside C2C12 cells. Collectively, MF is a
      potent antioxidant with a higher safety profile than ascorbic acid and myricetin.
      It reduces oxidative stress-induced delaying of skeletal muscle differentiation
      by scavenging reactive oxygen species and regulating myogenic proteins factors.

PMID- 28430435
TI  - Cu-In Halide Perovskite Solar Absorbers.
AB  - The long-term chemical instability and the presence of toxic Pb in otherwise
      stellar solar absorber APbX3 made of organic molecules on the A site and halogens
      for X have hindered their large-scale commercialization. Previously explored ways
      to achieve Pb-free halide perovskites involved replacing Pb2+ with other similar
      M2+ cations in ns2 electron configuration, e.g., Sn2+ or by Bi3+ (plus Ag+), but
      unfortunately this showed either poor stability (M = Sn) or weakly absorbing
      oversized indirect gaps (M = Bi), prompting concerns that perhaps stability and
      good optoelectronic properties might be contraindicated. Herein, we exploit the
      electronic structure underpinning of classic Cu[In,Ga]Se2 (CIGS) chalcopyrite
      solar absorbers to design Pb-free halide perovskites by transmuting 2Pb to the
      pair [BIB + CIII] such as [Cu + Ga] or [Ag + In] and combinations thereof. The
      resulting group of double perovskites with formula A2BCX6 (A = K, Rb, Cs; B = Cu,
      Ag; C = Ga, In; X = Cl, Br, I) benefits from the ionic, yet narrow-gap character
      of halide perovskites, and at the same time borrows the advantage of the strong
      Cu(d)/Se(p) -> Ga/In(s/p) valence-to-conduction-band absorption spectra known
      from CIGS. This constitutes a new group of CuIn-based Halide Perovskite (CIHP).
      Our first-principles calculations guided by such design principles indicate that
      the CIHPs class has members with clear thermodynamic stability, showing direct
      band gaps, and manifesting a wide-range of tunable gap values (from zero to about
      2.5 eV) and combination of light electron and heavy-light hole effective masses.
      Materials screening of candidate CIHPs then identifies the best-of-class
      Rb2[CuIn]Cl6, Rb2[AgIn]Br6, and Cs2[AgIn]Br6, having direct band gaps of 1.36,
      1.46, and 1.50 eV, and theoretical spectroscopic limited maximal efficiency
      comparable to chalcopyrites and CH3NH3PbI3. Our finding offers a new routine for
      designing new-type Pb-free halide perovskite solar absorbers.

PMID- 28430436
TI  - Time-Domain THz Spectroscopy Reveals Coupled Protein-Hydration Dielectric
      Response in Solutions of Native and Fibrils of Human Lysozyme.
AB  - Here we reveal details of the interaction between human lysozyme proteins, both
      native and fibrils, and their water environment by intense terahertz time domain
      spectroscopy. With the aid of a rigorous dielectric model, we determine the
      amplitude and phase of the oscillating dipole induced by the THz field in the
      volume containing the protein and its hydration water. At low concentrations, the
      amplitude of this induced dipolar response decreases with increasing
      concentration. Beyond a certain threshold, marking the onset of the interactions
      between the extended hydration shells, the amplitude remains fixed but the phase
      of the induced dipolar response, which is initially in phase with the applied THz
      field, begins to change. The changes observed in the THz response reveal protein
      protein interactions mediated by extended hydration layers, which may control
      fibril formation and may have an important role in chemical recognition
      phenomena.

PMID- 28430438
TI  - Controllable Synthesis of Lindqvist Alkoxopolyoxovanadate Clusters as
      Heterogeneous Catalysts for Sulfoxidation of Sulfides.
AB  - Six alkoxohexavanadate-based Cu- or Co-POVs [Cu(dpa)(acac)(H2O)]2[V6O13(OMe)6]
      (1), [Cu(phen)(acac)(MeOH)]2[V6O13(OMe)6] (2),
      [Co(dpa)(acac)2]2[V6O13(OMe)6].2MeOH (3), [Co(phen)(acac)2]2[V6O13(OMe)6] (4),
      [Cu(dpa)(acac)]2[VIV2VV4O12(OMe)7] (5), and
      [Cu(dpa)(acac)(MeOH)]2[VIV2VV4O11(OMe)8] (6) (POV = polyoxovanadate; dpa = 2,2'
      dipyridine amine; phen = 1,10-phenanthroline; acac = acetylacetone anion) have
      been synthesized by controlling the reaction conditions and characterized by
      single-crystal X-ray diffraction and powder X-ray diffraction analyses, FT-IR
      spectroscopy, element analyses, and X-ray photoelectron spectroscopy. In
      compounds 1-4 and 6, Cu or Co complexes and alkoxohexavanadate anions are
      assembled through electrostatic interactions. Differently, in compound 5, seven
      methoxo-substituted Lindqvist-type [V6O12(OMe)7]2- are bridged to Cu complex via
      terminal O atoms by coordination bonds. All compounds 1-6 exhibit excellent
      heterogeneous catalytic performance in oxidative desulfurization and CEES ((2
      chloroethyl) ethyl sulfide, a sulfur mustard simulant) abatement with H2O2 as
      oxidant. Among them, the catalytic activity of 6 [conv. of DBT (dibenzothiophene)
      up to 100% in 6 h; conv. of CEES reached 100% and selectivity of CEESO ((2
      chloroethyl) ethyl sulfoxide) up to 85% after 4 h] outperforms others and can be
      reused without losing its activity.

PMID- 28430437
TI  - Discovery of a Hepatitis C Virus NS5B Replicase Palm Site Allosteric Inhibitor
      (BMS-929075) Advanced to Phase 1 Clinical Studies.
AB  - The hepatitis C virus (HCV) NS5B replicase is a prime target for the development
      of direct-acting antiviral drugs for the treatment of chronic HCV infection.
      Inspired by the overlay of bound structures of three structurally distinct NS5B
      palm site allosteric inhibitors, the high-throughput screening hit anthranilic
      acid 4, the known benzofuran analogue 5, and the benzothiadiazine derivative 6,
      an optimization process utilizing the simple benzofuran template 7 as a starting
      point for a fragment growing approach was pursued. A delicate balance of
      molecular properties achieved via disciplined lipophilicity changes was essential
      to achieve both high affinity binding and a stringent targeted absorption,
      distribution, metabolism, and excretion profile. These efforts led to the
      discovery of BMS-929075 (37), which maintained ligand efficiency relative to
      early leads, demonstrated efficacy in a triple combination regimen in HCV
      replicon cells, and exhibited consistently high oral bioavailability and
      pharmacokinetic parameters across preclinical animal species. The human PK
      properties from the Phase I clinical studies of 37 were better than anticipated
      and suggest promising potential for QD administration.

PMID- 28430439
TI  - Molecular Organization of 2,1,3-Benzothiadiazoles in the Solid State.
AB  - Derivatives of 2,1,3-benzothiadiazole (1) are widely used in many areas of
      science and are particularly valuable as components of active layers in various
      thin-film optoelectronic devices. Even more effective benzothiadiazoles are
      likely to result if a deeper understanding of their preferred patterns of
      molecular association can be acquired. To provide new insight, we have analyzed
      the structures of compounds in which multiple benzothiadiazole units are attached
      to well-defined planar and nonplanar molecular cores. Our results show that
      molecular organization can be controlled in complex structures by using
      directional S...N bonding of benzothiadiazole units and other characteristic
      interactions. Moreover, the observed structures are distinctly different from
      those of analogous arenes. Replacing benzene rings in arenes by thiadiazoles
      thereby provides a strategy for making new compounds with extended systems of pi
      conjugation and unique patterns of molecular organization, including the ability
      to co-crystallize with the fullerenes C60 and C70.

PMID- 28430440
TI  - Insights on the Physical State Reached by an Active Pharmaceutical Ingredient
      upon High-Energy Milling.
AB  - We study the physicochemical transformations of crystalline quinidine upon high
      energy milling. The investigations have been achieved by classical, high
      performance, and fast scanning calorimetry combined with broadband dielectric
      spectroscopy and X-ray powder diffraction. As evolution of crystalline quinidine
      with time of milling revealed a prominent sub-Tg cold-crystallization phenomenon,
      independent and complementary analytical techniques were implemented. Fast
      scanning calorimetry was performed for the first time on a milled pharmaceutical
      compound to postpone the crystallization event to higher temperatures. These fast
      thermal analyses allowed one to spotlight a genuine glass transition event. In
      addition, an aging experiment on the milled powder revealed a clear structural
      relaxation testifying to the presence of a glassy fraction in the milled sample.
      Last, dielectric analysis of milled quinidine disclosed the presence of localized
      and delocalized molecular mobility characteristics of glasses. Results for
      samples obtained by two distinct amorphization routes, vitrification and high
      energy milling, indicate that amorphous fraction in milled quinidine behaves the
      same way as melt-quenched quinidine. These above-mentioned techniques proved
      their relevancy and efficiency to characterize milled quinidine, and fast
      scanning calorimetry in particular appears a promising screening tool for
      disordered systems.

PMID- 28430441
TI  - Oxygen-Bridged Diphenylnaphthylamine as a Scaffold for Full-Color Circularly
      Polarized Luminescent Materials.
AB  - An oxygen-bridged diphenylnaphthylamine with a helical shape was designed and
      synthesized as a key scaffold for circularly polarized luminescent (CPL)
      materials. The introduction of electron-withdrawing groups, such as formyl and
      2,2-dicyanovinyl substituents at the naphthyl moiety in this skeleton effectively
      decreases the LUMO level and thus allows a tuning of the band gap. The prepared
      model compounds exhibit intense CPL signals with a dissymmetry factor (g value)
      of 10-3 both in CH2Cl2 solutions and in the solid states. The emission colors of
      these derivatives are influenced both by the substituents as well as by solvent
      effects, covering the whole visible region from blue to deep red.

PMID- 28430442
TI  - Comment on "New Zeno-like Liquid States".

PMID- 28430443
TI  - Theoretical Investigation of the Binding of Nucleobases to Cucurbiturils by
      Dispersion Corrected DFT Approaches.
AB  - The encapsulation of nucleobases inside CB7 has gained prominence due to its use
      as anticancer and antiviral drugs. With this respect, the nonconvalent
      interactions existing in the nucleobases encapsulated inside the CB7 cavity have
      been analyzed employing the dispersion corrected density functional theory. The
      CBn cavity has the ability to encapsulate two guest nucleobases molecules when
      they are aligned in parallel configuration. The computed association energy using
      the two- and three-body correction method computed at B3LYP-D3 level is close to
      the experimental estimate. The use of dispersion corrected DFs is essential to
      identify the correct binding energies. The solvation energy plays a vital role in
      the estimation of association energy. QTAIM analysis shows that the Laplacian of
      the charge density (?2rho) is negative and the presence of covalent interaction
      between the guest and host molecule. The NCI-RDG isosurface shows the presence of
      noncovalent intermolecular interactions such as van der Waals and hydrogen
      bonding. The existence of "splattering" of charges in guanine@CB7 molecule is
      responsible for its higher stability. From the AIM, NCI-RDG, and EDA results, we
      conclude that noncovalent and electrostatic interaction with partial covalent
      character exists in the intermolecular bonding between the host and the guest
      nucleobases. The ramification of such intermolecular bonds is reflected in the 1H
      NMR and 13NMR spectra.

PMID- 28430444
TI  - Molecular Structuring and Percolation Transition in Hydrated Sulfonated
      Poly(ether ether ketone) Membranes.
AB  - The extent of phase separation and water percolation in sulfonated membranes are
      the key to their performance in fuel cells. Toward this, the effect of hydration
      on the morphology and transport characteristics of sulfonated poly(ether ether
      ketone), sPEEK, membrane is investigated using atomistic molecular dynamics
      simulation at various hydration levels(lambda: number of water molecules per
      sulfonate group). The evolution of local morphology is investigated using
      structural correlations and minimum pair distances. Transport properties are
      probed using mean squared displacements and diffusion coefficients. The water
      sulfonate interaction in sPEEK is found to be stronger than that in Nafion, as
      observed in experiments. Analyses indicate the presence of narrow connected path
      of water and hydronium at lambda = 4 and large domains, spanning half the
      simulation box, at lambda = 15. The behavior of membrane water remains far from
      bulk as indicated by its diffusion coefficient. The persistence of small isolated
      water clusters demonstrates the extent of phase separation in sPEEK to be lesser
      than that in Nafion. Analyses at molecular and collective levels suggest the
      occurrence of a percolation transition between lambda = 8 and 10, which leads to
      a connected network of water channels in the membrane, thereby boosting the
      hydronium mobility.

PMID- 28430445
TI  - Controlling the Roughness of Langmuir-Blodgett Monolayers.
AB  - Controlling the surface roughness of thin films with nanoscale precision is of
      significant interest for the rational design of surface coatings. Although
      wrinkling and buckling of Langmuir monolayers under compression has been
      demonstrated for several years, there is currently no method to precisely control
      this behavior during compression and thereby modify the surface roughness of
      deposited films. Here, we combine conventional Langmuir phase analysis with a
      novel dynamic viscoelasticity measurement to simply and accurately observe the
      jamming transition of monolayers of silica spheres, graphene oxide, and
      surfactant. By overcompressing beyond this point, the surface roughness of the
      deposited monolayer can be precisely controlled. This technique could be used to
      tune the surface properties of a variety of materials from lipids to
      nanoparticles.

PMID- 28430446
TI  - Piecing Together the Allosteric Patterns of Chaperonin GroEL.
AB  - Despite considerable efforts, elucidating the allostery of large macromolecular
      assemblies at a molecular level in solution remains technically challenging due
      to its structural complexity. Here we have employed an approach combining amide
      backbone hydrogen/deuterium exchange coupled with mass spectrometry, fluorescence
      spectroscopy, and molecular simulations to characterize allosteric patterns of
      chaperonin GroEL, an ~800 kDa tetradecamer from E. coli. Using available crystal
      structures of GroEL, we quantitatively map out GroEL allosteric changes in
      solution by resolving exchange behaviors of 133 overlapping proteolytic peptides
      with more than 95% sequence coverage. This comprehensive analysis gives a refined
      resolution down to five residues to pilot the GroEL allosteric determinants, of
      which the localized dynamics is monitored by tryptophan-mutated GroEL.
      Furthermore, the GroEL conformational transition is evaluated by molecular
      dynamics simulations with an atomic-interaction-based coarse-grained model.
      Collectively, we provide a practical methodology to analyze GroEL allostery in
      solution.

PMID- 28430447
TI  - Dehydrogenative Aromatic Ring Fusion for Carbazole Synthesis via C-C/C-N Bond
      Formation and Alkyl Migration.
AB  - An intermolecular dehydrogenative annulation (IDA) for carbazole synthesis via
      sequential C-C/C-N bond formation with a selective alkyl group migration is
      reported. Using the hypervalent iodine(III) reagent PhI(OAc)2 (PIDA), in a one
      pot operation, up to five C(sp2)-H bonds, one N(sp3)-H bond functionalization,
      and one alkyl (Me, Et) group migration could all be achieved from non
      prefunctionalized 1,3,5-trialkylbenzenes and anilides under ambient laboratory
      conditions. Mechanistically, it is shown that PIDA reacts with anilides to
      generate a nitrenium ion or an equivalent carbenium ion which influences the
      second aromatic ring to be activated for C-C/C-N bond formation. Strategically,
      regioselective fusion of arenes to anilides is described.

PMID- 28430448
TI  - Structural and Rheological Properties of Temperature-Responsive Amphiphilic
      Triblock Copolymers in Aqueous Media.
AB  - Thermoresponsive amphiphilic biodegradable block copolymers of the type
      poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol)-poly(epsilon
      caprolactone-co-lactide) (PCLA-PEGm-PCLA) have great potential for various
      biomedical applications. In the present study, we have surveyed the effects of
      PEG spacer length (m = 1000 and 1500), temperature, and polymer concentration on
      the self-assembling process to form supramolecular structures in aqueous
      solutions of the PCLA-PEGm-PCLA copolymer. This copolymer has a lower critical
      solution temperature, and the cloud point depends on both concentration and PEG
      length. Thermoreversible hydrogels are formed in the semidilute regime; the gel
      windows in the phase diagrams can be tuned by the concentration and length of the
      PEG spacer. The rheological properties of both dilute and semidilute samples were
      characterized; especially the sol-to-gel transition was examined. Small-angle
      neutron scattering (SANS) experiments reveal fundamental structural differences
      between the two copolymers for both dilute and semidilute samples. The intensity
      profiles for the copolymer with the long PEG spacer could be described by a
      spherical core-shell model over a broad temperature domain, whereas the copolymer
      with the short hydrophilic spacer forms rod-like species over an extended
      temperature range. This finding is supported by cryo-TEM images. At temperatures
      approaching macroscopic phase separation, both copolymers seem to assume extended
      rod-like structures.

PMID- 28430449
TI  - Rhodium-Catalyzed Alkenylation of C-H Bonds in Aromatic Amides with Alkynes.
AB  - The rhodium-catalyzed alkenylation of C-H bonds of aromatic amides with alkynes
      is reported. A variety of functional groups, including OMe, OAc, Br, Cl, and even
      NO2, are applicable to this reaction to give the corresponding hydroarylation
      products. The presence of an 8-aminoquinoline group as the directing group is
      crucial for the success of the reaction.

PMID- 28430450
TI  - Electrical Double-Layer and Ion Bridging Forces between Symmetric and Asymmetric
      Charged Surfaces in the Presence of Mono- and Divalent Ions.
AB  - An atomic force microscope, employing the colloidal probe technique, was used to
      study the interactions between six different combinations of silane
      functionalized silica surfaces in NaCl and CaCl2 solutions. The surfaces
      consisted of monolayers of the apolar trimethoxy(octyl)silane, the positively
      charged (3-aminopropyl)trimethoxysilane, and the negatively charged (3
      mercaptopropyl)trimethoxysilane. The interactions between the three symmetric
      systems, as well as between the three asymmetric combinations of surfaces, were
      measured and compared to calculated electrical double-layer forces. The results
      demonstrated that the long-range interactions between the surfaces in all cases
      were dominated by double-layer forces, while short-range interactions, including
      adhesion, were dominated by ion bridging forces in the cases where both
      interaction surfaces favored adsorption of calcium ions. The study thus also
      demonstrates how surface force studies in mono- and divalent salt solutions can
      be used as an analytical tool for probing specific functional groups on
      heterogeneous surfaces.

PMID- 28430451
TI  - Remote Asymmetric Bromination Reaction with Vinylketene Silyl N,O-Acetal and Its
      Application to Total Synthesis of Pellasoren A.
AB  - Stereoselective bromination of the E,E-vinylketene silyl N,O-acetal possessing a
      chiral auxiliary has been achieved and applied to introduction of heteroatom at
      gamma-position of alpha,beta-unsaturated imide. The reactions proceeded in high
      stereoselectivity. Total synthesis of pellasoren A, an antitumor propionate from
      the myxobacteriun Sorangium cellulosum, has been accomplished in short steps by
      this methodology and our method of reduced polypropionate synthesis.

PMID- 28430452
TI  - Demystifying Complex Quantum Dot Heterostructures Using Photogenerated Charge
      Carriers.
AB  - The success of heterostructure quantum dots in optoelectronic and photovoltaic
      applications is based on our understanding of photogenerated charge carrier
      localization. However, often the actual location of charge carriers in
      heterostructure semiconductors is quite different from their predicted positions
      leading to suboptimal results. In this work, photoluminescence of Cu doped
      heterostructures has been used to study the charge localization of alloys,
      inverse type I, type II, and quasi type II core/shell structures and graded
      alloys. Specifically, the adeptness of this method has been assessed over a range
      of widely studied heterostructures like CdSe/CdS, CdS/CdSe, CdSe/CdTe, Zn1-xCdxSe
      and Zn1-xCdxS quantum dots systems by doping them with a small percentage of Cu.
      The electron and hole localization obtained from this method concurs with the pre
      existing understanding in cases that have been explored before, while the
      internal structure of previously unknown heterostructures have been predicted.

PMID- 28430453
TI  - Ag-Initiated gem-Difluoromethylenation of the Nitrogen Center of Arenediazonium
      Salts to gem-Difluoromethylene Azo Compounds.
AB  - An efficient method for the synthesis of the thermally stable and
      pharmaceutically important gem-difluoromethylene azo compounds is developed. This
      protocol achieved gem-difluoromethylenation of the nitrogen center of
      arenediazonium salts through in situ generated benzo-1,3-diazolic
      difluoromethylene radical addition to arenediazonium salts under mild Ag
      initiated conditions.

PMID- 28430454
TI  - Accessing Polyoxygenated Dibenzofurans via the Union of Phenols and o
      Benzoquinones: Rapid Syntheses of Metabolites Isolated from Ribes takare.
AB  - The construction of polyoxygenated dibenzo[b,d]furan frameworks from the union of
      substituted phenols/naphthols and o-benzoquinones via a Michael-oxidation-oxa
      Michael cascade is reported. The power of this transformation is demonstrated in
      the generation of a library of highly substituted dibenzofurans, featuring
      specifically substituted molecules containing broad ranges of functionality. The
      utility of this method is showcased in the total syntheses of two dibenzofurans
      isolated from Ribes takare, assembling the carbon scaffold of both natural
      products in one operation.

PMID- 28430455
TI  - Synthesis of Dihydropyridinone-Fused Indoles and alpha-Carbolines via N
      Heterocyclic Carbene-Catalyzed [3 + 3] Annulation of Indolin-2-imines and
      Bromoenals.
AB  - The N-heterocyclic carbene catalyzed [3 + 3] annulation of indolin-2-imines and
      bromoenals was developed to give dihydropyridinone-fused indoles in good to high
      yields, which were transformed to alpha-carbolines with different 2-subsituents
      by a process of dehydrogenation, tosylation, and palladium catalyzed C-C or C-N
      coupling reaction.

PMID- 28430456
TI  - Microstructure of beta-Sitosterol:gamma-Oryzanol Edible Organogels.
AB  - Rheology and atomic force microscopy (AFM) were employed to examine the
      microstructure of beta-sitosterol:gamma-oryzanol organogels in sunflower oil.
      Using time-resolved rheology, we followed gel formation, paying specific
      attention to the fibril aggregation process, which had not been studied in detail
      previously for this system. Using AFM, we observed gel structures directly and
      obtained detailed information on the gel structure, far exceeding previous
      studies. Our analysis suggests that though gels are formed by the self-assembly
      and aggregation of one-dimensional fibrils, the manner in which these fibrils
      aggregate into ribbons results in complex structures of higher dimensionality. We
      emphasize that it is a surprise to find ribbons and not twisted strands.
      Comparing AFM images of 10% w/w and 20% w/w gelator systems, we observed
      differences in the degree of branching which are consistent with the rheology. We
      also observed the individual self-assembled fibrils which make up these gels with
      much greater clarity than in previous microscopy studies, and the fibril
      diameters of ~9.8 nm we measured agree excellently with those obtained from
      existing small-angle neutron scattering data. These results provide new insight
      into the structure and formation kinetics of this important organogel system.

PMID- 28430457
TI  - Classical Spin Liquid Instability Driven By Off-Diagonal Exchange in Strong Spin
      Orbit Magnets.
AB  - We show that the off-diagonal exchange anisotropy drives Mott insulators with
      strong spin-orbit coupling to a classical spin liquid regime, characterized by an
      infinite number of ground states and Ising variables living on closed or open
      strings. Depending on the sign of the anisotropy, quantum fluctuations either
      fail to lift the degeneracy down to very low temperatures, or select noncoplanar
      magnetic states with unconventional spin correlations. The results apply to all
      2D and 3D tricoordinated materials with bond-directional anisotropy and provide a
      consistent interpretation of the suppression of the x-ray magnetic circular
      dichroism signal reported recently for beta-Li_{2}IrO_{3} under pressure.

PMID- 28430458
TI  - Gating Classical Information Flow via Equilibrium Quantum Phase Transitions.
AB  - The development of communication channels at the ultimate size limit of atomic
      scale physical dimensions will make the use of quantum entities an imperative. In
      this regime, quantum fluctuations naturally become prominent and are generally
      considered to be detrimental. Here, we show that for spin-based information
      processing, these fluctuations can be uniquely exploited to gate the flow of
      classical binary information across a magnetic chain in thermal equilibrium.
      Moreover, this information flow can be controlled with a modest external magnetic
      field that drives the system through different many-body quantum phases in which
      the orientation of the final spin does or does not reflect the orientation of the
      initial input. Our results are general for a wide class of anisotropic spin
      chains that act as magnetic cellular automata and suggest that quantum phase
      transitions play a unique role in driving classical information flow at the
      atomic scale.

PMID- 28430459
TI  - Direct Observation of Percolation in the Yielding Transition of Colloidal
      Glasses.
AB  - When strained beyond the linear regime, soft colloidal glasses yield to steady
      state plastic flow in a way that is similar to the deformation of conventional
      amorphous solids. Because of the much larger size of the colloidal particles with
      respect to the atoms comprising an amorphous solid, colloidal glasses allow us to
      obtain microscopic insight into the nature of the yielding transition, as we
      illustrate here combining experiments, atomistic simulations, and mesoscopic
      modeling. Our results unanimously show growing clusters of nonaffine deformation
      percolating at yielding. In agreement with percolation theory, the spanning
      cluster is fractal with a fractal dimension d_{f}?2, and the correlation length
      diverges upon approaching the critical yield strain. These results indicate that
      percolation of highly nonaffine particles is the hallmark of the yielding
      transition in disordered glassy systems.

PMID- 28430460
TI  - Subradiance via Entanglement in Atoms with Several Independent Decay Channels.
AB  - Spontaneous emission of atoms in free space is modified by the presence of other
      atoms in close vicinity inducing collective super- and subradiance. For two
      nearby atoms with a single decay channel the entangled antisymmetric
      superposition state of the two single excited states will not decay
      spontaneously. No such excited two-atom dark state exists, if the excited state
      has two independent optical decay channels of different frequencies or
      polarizations. However, we show that for an excited atomic state with N-1
      independent spontaneous decay channels one can find a highly entangled N-particle
      dark state, which completely decouples from the vacuum radiation field. It does
      not decay spontaneously, nor will it absorb resonant laser light. Mathematically,
      we see that this state is the only such state orthogonal to the subspace spanned
      by the atomic ground states. Moreover, by means of generic numerical examples we
      demonstrate that the subradiant behavior largely survives at finite atomic
      distances including dipole-dipole interactions.

PMID- 28430461
TI  - Quantifying the Dynamical Complexity of Chaotic Time Series.
AB  - A powerful approach is proposed for the characterization of chaotic signals. It
      is based on the combined use of two classes of indicators: (i) the probability of
      suitable symbolic sequences (obtained from the ordinal patterns of the
      corresponding time series); (ii) the width of the corresponding cylinder sets.
      This way, much information can be extracted and used to quantify the complexity
      of a given signal. As an example of the potentiality of the method, I introduce a
      modified permutation entropy which allows for quantitative estimates of the
      Kolmogorov-Sinai entropy in hyperchaotic models, where other methods would be
      unpractical. As a by-product, estimates of the fractal dimension of the
      underlying attractors are possible as well.

PMID- 28430462
TI  - Fuzzy Dark Matter from Infrared Confining Dynamics.
AB  - A very light boson of mass O(10^{-22})  eV may potentially be a viable dark
      matter (DM) candidate, which can avoid phenomenological problems associated with
      cold DM. Such "fuzzy DM (FDM)" may naturally be an axion with a decay constant
      f_{a}~10^{16}-10^{18}  GeV and a mass m_{a}~MU^{2}/f_{a} with MU~10^{2}  eV.
      Here, we propose a concrete model, where MU arises as a dynamical scale from
      infrared confining dynamics, analogous to QCD. Our model is an alternative to the
      usual approach of generating MU through string theoretic instanton effects. We
      outline the features of this scenario that result from various cosmological
      constraints. We find that those constraints are suggestive of a period of mild of
      inflation, perhaps from a strong first order phase transition, that reheats the
      standard model (SM) sector only. A typical prediction of our scenario, broadly
      speaking, is a larger effective number of neutrinos compared to the SM value
      N_{eff}~3, as inferred from precision measurements of the cosmic microwave
      background. Some of the new degrees of freedom may be identified as "sterile
      neutrinos," which may be required to explain certain neutrino oscillation
      anomalies. Hence, aspects of our scenario could be testable in terrestrial
      experiments, which is a novelty of our FDM model.

PMID- 28430463
TI  - Electromagnetic Response of Three-Dimensional Topological Crystalline Insulators.
AB  - Topological crystalline insulators are a new class of materials that have
      metallic surface states on select surfaces due to point group crystalline
      symmetries. In this Letter, we consider a model for a three-dimensional
      topological crystalline insulator with Dirac nodes occurring on a surface that
      are protected by the mirror symmetry. We demonstrate that the electromagnetic
      response for such a system is characterized by a 1-form b_{MU}. The value of
      b_{MU} can be inferred from the locations of the surface Dirac nodes in energy
      momentum space. From both the effective action and analytical band structure
      calculations, we show that the vortex core of b[over ->] or a domain wall of a
      component of b[over ->] can trap surface charges.

PMID- 28430464
TI  - Accurate Determination of the Quasiparticle and Scaling Properties Surrounding
      the Quantum Critical Point of Disordered Three-Dimensional Dirac Semimetals.
AB  - Exploiting the enabling power of the Lanczos method in momentum space, we
      determine accurately the quasiparticle and scaling properties of disordered three
      dimensional Dirac semimetals surrounding the quantum critical point separating
      the semimetal and diffusive metal regimes. We unveil that the imaginary part of
      the quasiparticle self-energy obeys a common power law before, at, and after the
      quantum phase transition, but the power law is nonuniversal, whose exponent is
      dependent on the disorder strength. More intriguingly, whereas a common power law
      is also found for the real part of the self-energy before and after the phase
      transition, a distinctly different behavior is identified at the critical point,
      characterized by the existence of a nonanalytic logarithmic singularity. This
      nonanalytical correction serves as the very basis for the unusual power-law
      behaviors of the quasiparticles and many other physical properties surrounding
      the quantum critical point. Our approach also allows the ready and reliable
      determination of the scaling properties of the correlation length and dynamical
      exponents. We further show that the central findings are valid for both
      uncorrelated and correlated disorder distributions and should be directly
      comparable with future experimental observations.

PMID- 28430465
TI  - Elemental Topological Dirac Semimetal: alpha-Sn on InSb(111).
AB  - Three-dimensional (3D) topological Dirac semimetals (TDSs) are rare but important
      as a versatile platform for exploring exotic electronic properties and
      topological phase transitions. A quintessential feature of TDSs is 3D Dirac
      fermions associated with bulk electronic states near the Fermi level. Using angle
      resolved photoemission spectroscopy, we have observed such bulk Dirac cones in
      epitaxially grown alpha-Sn films on InSb(111), the first such TDS system realized
      in an elemental form. First-principles calculations confirm that epitaxial strain
      is key to the formation of the TDS phase. A phase diagram is established that
      connects the 3D TDS phase through a singular point of a zero-gap semimetal phase
      to a topological insulator phase. The nature of the Dirac cone crosses over from
      3D to 2D as the film thickness is reduced.

PMID- 28430466
TI  - Evidence for Anomalous Dynamic Heterogeneities in Isostatic Supercooled Liquids.
AB  - Upon cooling, the dynamics of supercooled liquids exhibits a growing transient
      spatial distribution of relaxation times that is known as dynamic
      heterogeneities. The relationship between this now well-established crucial
      feature of the glass transition and some underlying liquid properties remains
      challenging and elusive in many respects. Here we report on computer simulations
      of liquids with a changing network structure (densified silicates), and show that
      there is a deep and important link between the mechanical nature characterized by
      topological constraints and the spatial extent of such fluctuations. This is not
      only revealed by a maximum in the dynamic correlation length xi_{4} for
      fluctuations when the liquid becomes isostatically rigid, but also by a
      contraction of the volume of relaxing structural correlations upon the onset of
      stressed rigidity.

PMID- 28430467
TI  - Zero-Field Skyrmions with a High Topological Number in Itinerant Magnets.
AB  - Magnetic Skyrmions are swirling spin textures with topologically protected
      noncoplanarity. Recently, Skyrmions with the topological number of unity have
      been extensively studied in both experiment and theory. We here show that a
      Skyrmion crystal with an unusually high topological number of two is stabilized
      in itinerant magnets at a zero magnetic field. The results are obtained for a
      minimal Kondo lattice model on a triangular lattice by an unrestricted large
      scale numerical simulation and variational calculations. We find that the
      topological number can be switched by a magnetic field as 2<->1<->0. The Skyrmion
      crystals are formed by the superpositions of three spin density waves induced by
      the Fermi surface effect, and hence, the size of Skyrmions can be controlled by
      the band structure and electron filling. We also discuss the charge and spin
      textures of itinerant electrons in the Skyrmion crystals which are directly
      obtained in our numerical simulations.

PMID- 28430468
TI  - Yangian Symmetry and Integrability of Planar N=4 Supersymmetric Yang-Mills
      Theory.
AB  - In this Letter, we establish Yangian symmetry of planar N=4 supersymmetric Yang
      Mills theory. We prove that the classical equations of motion of the model close
      onto themselves under the action of Yangian generators. Moreover, we propose an
      off-shell extension of our statement, which is equivalent to the invariance of
      the action and prove that it is exactly satisfied. We assert that our
      relationship serves as a criterion for integrability in planar gauge theories by
      explicitly checking that it applies to the integrable Aharony-Bergman-Jafferis
      Maldacena theory but not to the nonintegrable N=1 supersymmetric Yang-Mills
      theory.

PMID- 28430469
TI  - Bell Correlations in Spin-Squeezed States of 500 000 Atoms.
AB  - Bell correlations, indicating nonlocality in composite quantum systems, were
      until recently only seen in small systems. Here, we demonstrate Bell correlations
      in squeezed states of 5*10^{5} ^{87}Rb atoms. The correlations are inferred using
      collective measurements as witnesses and are statistically significant to 124
      standard deviations. The states are both generated and characterized using
      optical-cavity aided measurements.

PMID- 28430470
TI  - Parametrically Tunable Soliton-Induced Resonant Radiation by Three-Wave Mixing.
AB  - We show that a temporal soliton can induce resonant radiation by three-wave
      mixing nonlinearities. This constitutes a new class of resonant radiation whose
      spectral positions are parametrically tunable. The experimental verification is
      done in a periodically poled lithium niobate crystal, where a femtosecond near-IR
      soliton is excited and resonant radiation waves are observed exactly at the
      calculated soliton phase-matching wavelengths via the sum- and difference
      frequency generation nonlinearities. This extends the supercontinuum bandwidth
      well into the mid IR to span 550-5000 nm, and the mid-IR edge is parametrically
      tunable over 1000 nm by changing the three-wave mixing phase-matching condition.
      The results are important for the bright and broadband supercontinuum generation
      and for the frequency comb generation in quadratic nonlinear microresonators.

PMID- 28430471
TI  - Detection and Control of Spin-Orbit Interactions in a GaAs Hole Quantum Point
      Contact.
AB  - We investigate the relationship between the Zeeman interaction and the inversion
      asymmetry-induced spin-orbit interactions (Rashba and Dresselhaus SOIs) in GaAs
      hole quantum point contacts. The presence of a strong SOI results in the crossing
      and anticrossing of adjacent spin-split hole subbands in a magnetic field. We
      demonstrate theoretically and experimentally that the anticrossing energy gap
      depends on the interplay between the SOI terms and the highly anisotropic hole g
      tensor and that this interplay can be tuned by selecting the crystal axis along
      which the current and magnetic field are aligned. Our results constitute the
      independent detection and control of the Dresselhaus and Rashba SOIs in hole
      systems, which could be of importance for spintronics and quantum information
      applications.

PMID- 28430472
TI  - Random Number Generation with Cosmic Photons.
AB  - Random numbers are indispensable for a variety of applications ranging from
      testing physics foundations to information encryption. In particular, nonlocality
      test provide strong evidence for our current understanding of nature-quantum
      mechanics. All the random number generators (RNGs) used for the existing tests
      are constructed locally, making the test results vulnerable to the freedom-of
      choice loophole. We report an experimental realization of RNGs based on the
      arrival time of cosmic photons. The measurement outcomes (raw data) pass the
      standard NIST statistical test suite. We present a realistic design to employ
      these RNGs in a Bell test experiment, which addresses the freedom-of-choice
      loophole.

PMID- 28430474
TI  - Dispersion Management of Propagating Waveguide Modes on the Water Surface.
AB  - We report on the theoretical and experimental study of the generation of
      propagating waveguide modes on the water surface. These propagating modes are
      modulated in the transverse direction in a manner that satisfies boundary
      conditions on the walls of the water tank. It is shown that the propagating modes
      possess both anomalous and normal dispersion regimes, in contrast to the
      extensively studied zero mode that, in the case of deep water, only has normal
      dispersion with a fixed frequency independent dispersion coefficient.
      Importantly, by using a carrier frequency at which the group velocity dispersion
      crosses zero, a linear nonspreading and shape-preserving wave packet is observed.
      By increasing the wave steepness, nonlinear effects become pronounced, thereby
      enabling the first observation of linearly chirped parabolic water wave pulses in
      the anomalous dispersion regime. This parabolic wave maintains its linear
      frequency chirp and does not experience wave breaking during propagation.

PMID- 28430473
TI  - First Direct-Detection Constraints on eV-Scale Hidden-Photon Dark Matter with
      DAMIC at SNOLAB.
AB  - We present direct detection constraints on the absorption of hidden-photon dark
      matter with particle masses in the range 1.2-30  eV c^{-2} with the DAMIC
      experiment at SNOLAB. Under the assumption that the local dark matter is entirely
      constituted of hidden photons, the sensitivity to the kinetic mixing parameter
      kappa is competitive with constraints from solar emission, reaching a minimum
      value of 2.2*10^{-14} at 17  eV c^{-2}. These results are the most stringent
      direct detection constraints on hidden-photon dark matter in the galactic halo
      with masses 3-12  eV c^{-2} and the first demonstration of direct experimental
      sensitivity to ionization signals <12  eV from dark matter interactions.

PMID- 28430475
TI  - Amplitude Mode in Three-Dimensional Dimerized Antiferromagnets.
AB  - The amplitude ("Higgs") mode is a ubiquitous collective excitation related to
      spontaneous breaking of a continuous symmetry. We combine quantum Monte Carlo
      (QMC) simulations with stochastic analytic continuation to investigate the
      dynamics of the amplitude mode in a three-dimensional dimerized quantum spin
      system. We characterize this mode by calculating the spin and dimer spectral
      functions on both sides of the quantum critical point, finding that both the
      energies and the intrinsic widths of the excitations satisfy field-theoretical
      scaling predictions. While the line width of the spin response is close to that
      observed in neutron scattering experiments on TlCuCl_{3}, the dimer response is
      significantly broader. Our results demonstrate that highly nontrivial dynamical
      properties are accessible by modern QMC and analytic continuation methods.

PMID- 28430476
TI  - Generalized Pseudopotentials for the Anisotropic Fractional Quantum Hall Effect.
AB  - We generalize the notion of Haldane pseudopotentials to anisotropic fractional
      quantum Hall (FQH) systems that are physically realized, e.g., in tilted magnetic
      field experiments or anisotropic band structures. This formalism allows us to
      expand any translation-invariant interaction over a complete basis, and directly
      reveals the intrinsic metric of incompressible FQH fluids. We show that purely
      anisotropic pseudopotentials give rise to new types of bound states for small
      particle clusters in the infinite plane, and can be used as a diagnostic of FQH
      nematic order. We also demonstrate that generalized pseudopotentials quantify the
      anisotropic contribution to the effective interaction potential, which can be
      particularly large in models of fractional Chern insulators.

PMID- 28430477
TI  - Spatiotemporal Patterns in Ultraslow Domain Wall Creep Dynamics.
AB  - In the presence of impurities, ferromagnetic and ferroelectric domain walls slide
      only above a finite external field. Close to this depinning threshold, they
      proceed by large and abrupt jumps called avalanches, while, at much smaller
      fields, these interfaces creep by thermal activation. In this Letter, we develop
      a novel numerical technique that captures the ultraslow creep regime over huge
      time scales. We point out the existence of activated events that involve
      collective reorganizations similar to avalanches, but, at variance with them,
      display correlated spatiotemporal patterns that resemble the complex sequence of
      aftershocks observed after a large earthquake. Remarkably, we show that events
      assemble in independent clusters that display at large scales the same statistics
      as critical depinning avalanches. We foresee these correlated dynamics being
      experimentally accessible by magnetooptical imaging of ferromagnetic films.

PMID- 28430478
TI  - Premelting hcp to bcc Transition in Beryllium.
AB  - Beryllium (Be) is an important material with wide applications ranging from
      aerospace components to x-ray equipment. Yet a precise understanding of its phase
      diagram remains elusive. We have investigated the phase stability of Be using a
      recently developed hybrid free energy computation method that accounts for
      anharmonic effects by invoking phonon quasiparticles. We find that the hcp -> bcc
      transition occurs near the melting curve at 0<P<11  GPa with a positive Clapeyron
      slope of 41+/-4  K/GPa, which is more consistent with recent experimental
      measurements. This work also demonstrates the validity of this theoretical
      framework based on the phonon quasiparticle to study the structural stability and
      phase transitions in strongly anharmonic materials.

PMID- 28430479
TI  - Interfacing Superconducting Qubits and Single Optical Photons Using Molecules in
      Waveguides.
AB  - We propose an efficient light-matter interface at optical frequencies between a
      single photon and a superconducting qubit. The desired interface is based on a
      hybrid architecture composed of an organic molecule embedded inside an optical
      waveguide and electrically coupled to a superconducting qubit placed near the
      outside surface of the waveguide. We show that high fidelity, photon-mediated,
      entanglement between distant superconducting qubits can be achieved with incident
      pulses at the single photon level. Such a low light level is highly desirable for
      achieving a coherent optical interface with superconducting qubit, since it
      minimizes decoherence arising from the absorption of light.

PMID- 28430480
TI  - Superconducting Grid-Bus Surface Code Architecture for Hole-Spin Qubits.
AB  - We present a scalable hybrid architecture for the 2D surface code combining
      superconducting resonators and hole-spin qubits in nanowires with tunable direct
      Rashba spin-orbit coupling. The backbone of this architecture is a square lattice
      of capacitively coupled coplanar waveguide resonators each of which hosts a
      nanowire hole-spin qubit. Both the frequency of the qubits and their coupling to
      the microwave field are tunable by a static electric field applied via the
      resonator center pin. In the dispersive regime, an entangling two-qubit gate can
      be realized via a third order process, whereby a virtual photon in one resonator
      is created by a first qubit, coherently transferred to a neighboring resonator,
      and absorbed by a second qubit in that resonator. Numerical simulations with
      state-of-the-art coherence times yield gate fidelities approaching the 99% fault
      tolerance threshold.

PMID- 28430481
TI  - Ultimate Limit in the Spectral Resolution of Extreme Ultraviolet Frequency Combs.
AB  - We present the results of direct interferometric measurements on the pulse-to
      pulse phase jitter of a metrological, fiber-based, infrared (IR) frequency comb.
      We show that the short-time evolution of such phase fluctuations, which cannot be
      actively controlled by any feedback system, imposes a stringent limit on the
      tooth linewidth of extreme ultraviolet (XUV) combs produced by high-order
      harmonic conversion, thus explaining the difference of 9 orders of magnitude
      between the coherence times of state-of-the-art IR and XUV frequency combs.

PMID- 28430482
TI  - Hopping Time Scales and the Phonon-Liquid Electron-Crystal Picture in
      Thermoelectric Copper Selenide.
AB  - The suppression of transverse phonons by liquidlike diffusion in superionic
      conductors has been proposed as a means to dramatically reduce thermal
      conductivity in thermoelectric materials [H. Lui et al. Nat. Mater. 11, 422
      (2012)NMAACR1476-112210.1038/nmat3273]. We have measured the ion transport and
      lattice dynamics in the original phonon-liquid electron-crystal Cu_{2}Se using
      neutron spectroscopy. We show that hopping time scales are too slow to
      significantly affect lattice vibrations and that the transverse phonons persist
      at all temperatures. Substantial changes to the phonon spectrum occur well below
      the transition to the superionic phase, and the ultralow thermal conductivity is
      instead attributed to anharmonicity.

PMID- 28430483
TI  - Infrared Peak Splitting from Phonon Localization in Solid Hydrogen.
AB  - We show that the isotope effect leads to a completely different spectroscopic
      signal in hydrogen-deuterium mixtures, compared to pure elements that have the
      same crystal structure. This is particularly true for molecular vibrations, which
      are the main source of information about the structure of high-pressure hydrogen.
      Mass disorder breaks translational symmetry, meaning that vibrations are
      localized almost to single molecules, and are not zone-center phonons. In
      mixtures, each observable infrared (IR) peak corresponds to a collection of many
      such molecular vibrations, which have a distribution of frequencies depending on
      local environment. Furthermore discrete groups of environments cause the peaks to
      split. We illustrate this issue by considering the IR spectrum of the high
      pressure phase III structure of hydrogen, recently interpreted as showing novel
      phases in isotopic mixtures. We calculate the IR spectrum of hydrogen-deuterium
      mixtures in the C2/c and Cmca-12 structures, showing that isotopic disorder gives
      rise to mode localization of the high-frequency vibrons. The local coordination
      of the molecules leads to discrete IR peaks. The spread of frequencies is
      strongly enhanced with pressure, such that more peaks become resolvable at higher
      pressures, in agreement with the recent measurements.

PMID- 28430484
TI  - Lattice Prediction for Deeply Bound Doubly Heavy Tetraquarks.
AB  - We investigate the possibility of qq^{'}b[over -]b[over -] tetraquark bound
      states using n_{f}=2+1 lattice QCD ensembles with pion masses ?164, 299, and 415
      MeV. Motivated by observations from heavy baryon phenomenology, we consider two
      lattice interpolating operators, both of which are expected to couple efficiently
      to tetraquark states: one with a diquark-antidiquark and one with a meson-meson
      structure. Using nonrelativistic QCD to simulate the bottom quarks, we study the
      udb[over -]b[over -], lsb[over -]b[over -] channels with l=u, d, and find
      unambiguous signals for strong-interaction-stable J^{P}=1^{+} tetraquarks. These
      states are found to lie 189(10) and 98(7) MeV below the corresponding free two
      meson thresholds.

PMID- 28430485
TI  - Coherent Coupling of Remote Spin Ensembles via a Cavity Bus.
AB  - We report coherent coupling between two macroscopically separated nitrogen
      vacancy electron spin ensembles in a cavity quantum electrodynamics system. The
      coherent interaction between the distant ensembles is directly detected in the
      cavity transmission spectrum by observing bright and dark collective
      multiensemble states and an increase of the coupling strength to the cavity mode.
      Additionally, in the dispersive limit we show transverse ensemble-ensemble
      coupling via virtual photons.

PMID- 28430486
TI  - Fluctuations and Topological Defects in Proper Ferroelectric Crystals.
AB  - Homotopy theory and first-principles-based effective Hamiltonian simulations are
      combined to investigate the stability of topological defects in proper
      ferroelectric crystals. We show that, despite a nearly trivial topology of the
      order parameter space, these materials can exhibit stable topological point
      defects in their tetragonal polar phase and stable topological line defects in
      their orthorhombic polar phase. The stability of such defects originates from a
      novel mechanism of topological protection related to finite-temperature
      fluctuations of local dipoles.

PMID- 28430487
TI  - Population Mixing in Asymmetric Magnetic Reconnection with a Guide Field.
AB  - We investigate how population mixing leads to structured electron distribution
      functions in asymmetric guide-field magnetic reconnection based on particle-in
      cell simulations. The change of magnetic connectivity patches populations from
      different inflow regions to form multicomponent distributions in the exhaust,
      illustrating the direct consequence of the breaking and rejoining of magnetic
      flux tubes. Finite Larmor radius (FLR) effects of electrons accelerated by the
      perpendicular electric fields result in crescent-type nongyrotropic
      distributions. A new type of nongyrotropy is found to be caused by the combined
      effects of the FLR and velocity dispersion of electrons accelerated by the
      parallel electric field. The patching together of populations and the effects of
      acceleration and the FLR form the first steps of mixing in the exhaust and
      separatrix regions.

PMID- 28430489
TI  - Absence of a Large Superconductivity-Induced Gap in Magnetic Fluctuations of
      Sr_{2}RuO_{4}.
AB  - Inelastic neutron scattering experiments on Sr_{2}RuO_{4} determine the spectral
      weight of the nesting induced magnetic fluctuations across the superconducting
      transition. There is no observable change at the superconducting transition down
      to an energy of ~0.35  meV, which is well below the 2Delta values reported in
      several tunneling experiments. At this and higher energies magnetic fluctuations
      clearly persist in the superconducting state. Only at energies below ~0.3  meV
      can evidence for partial suppression of spectral weight in the superconducting
      state be observed. This strongly suggests that the one-dimensional bands with the
      associated nesting fluctuations do not form the active, highly gapped bands in
      the superconducting pairing in Sr_{2}RuO_{4}.

PMID- 28430490
TI  - Diffused Vorticity and Moment of Inertia of a Spin-Orbit Coupled Bose-Einstein
      Condensate.
AB  - By developing the hydrodynamic theory of spinor superfluids, we calculate the
      moment of inertia of a harmonically trapped Bose-Einstein condensate with spin
      orbit coupling. We show that the velocity field associated with the rotation of
      the fluid exhibits diffused vorticity, in contrast to the irrotational behavior
      characterizing a superfluid. Both Raman-induced and Rashba spin-orbit couplings
      are considered. In the first case the moment of inertia takes the rigid value at
      the transition between the plane wave and the single minimum phase, while in the
      latter case the rigid value is achieved in the limit of isotropic Rashba
      coupling. A procedure to generate the rigid rotation of the fluid and to measure
      the moment of inertia is proposed. The quenching of the quantum of circulation
      h/m, caused by Raman-induced spin-orbit coupling in a toroidal geometry, is also
      discussed.

PMID- 28430491
TI  - Thermal Hall Effect in a Phonon-Glass Ba_{3}CuSb_{2}O_{9}.
AB  - A distinct thermal Hall signal is observed in a quantum spin liquid candidate
      Ba_{3}CuSb_{2}O_{9}. The transverse thermal conductivity shows a power-law
      temperature dependence below 50 K, where a spin gap opens. We suggest that
      because of the very low longitudinal thermal conductivity and the thermal Hall
      signals, a phonon Hall effect is induced by strong phonon scattering of orphan
      Cu^{2+} spins formed in the random domains of the Cu^{2+}-Sb^{5+} dumbbells in
      Ba_{3}CuSb_{2}O_{9}.

PMID- 28430492
TI  - High-T_{c} Superconductivity in FeSe at High Pressure: Dominant Hole Carriers and
      Enhanced Spin Fluctuations.
AB  - The importance of electron-hole interband interactions is widely acknowledged for
      iron-pnictide superconductors with high transition temperatures (T_{c}). However,
      the absence of hole pockets near the Fermi level of the iron-selenide (FeSe)
      derived high-T_{c} superconductors raises a fundamental question of whether iron
      pnictides and chalcogenides have different pairing mechanisms. Here, we study the
      properties of electronic structure in the high-T_{c} phase induced by pressure in
      bulk FeSe from magnetotransport measurements and first-principles calculations.
      With increasing pressure, the low-T_{c} superconducting phase transforms into the
      high-T_{c} phase, where we find the normal-state Hall resistivity changes sign
      from negative to positive, demonstrating dominant hole carriers in contrast to
      other FeSe-derived high-T_{c} systems. Moreover, the Hall coefficient is enlarged
      and the magnetoresistance exhibits anomalous scaling behaviors, evidencing
      strongly enhanced interband spin fluctuations in the high-T_{c} phase. These
      results in FeSe highlight similarities with high-T_{c} phases of iron pnictides,
      constituting a step toward a unified understanding of iron-based
      superconductivity.

PMID- 28430493
TI  - Limits on Lorentz Invariance Violation from Coulomb Interactions in Nuclei and
      Atoms.
AB  - Anisotropy in the speed of light that has been constrained by Michelson-Morley
      type experiments also generates anisotropy in the Coulomb interactions. This
      anisotropy can manifest itself as an energy anisotropy in nuclear and atomic
      experiments. Here the experimental limits on Lorentz violation in _{10}^{21}Ne
      are used to improve the limits on Lorentz symmetry violations in the photon
      sector, namely, the anisotropy of the speed of light and the Coulomb
      interactions, by 7 orders of magnitude in comparison with previous experiments:
      the speed of light is isotropic to a part in 10^{28}.

PMID- 28430494
TI  - Quantum Simulation of Generic Many-Body Open System Dynamics Using Classical
      Noise.
AB  - We introduce a scheme for the quantum simulation of many-body decoherence based
      on the unitary evolution of a stochastic Hamiltonian. Modulating the strength of
      the interactions with stochastic processes, we show that the noise-averaged
      density matrix simulates an effectively open dynamics governed by k-body Lindblad
      operators. Markovian dynamics can be accessed with white-noise fluctuations; non
      Markovian dynamics requires colored noise. The time scale governing the fidelity
      decay under many-body decoherence is shown to scale as N^{-2k} with the system
      size N. Our proposal can be readily implemented in a variety of quantum platforms
      including optical lattices, superconducting circuits, and trapped ions.

PMID- 28430495
TI  - Superstatistical Energy Distributions of an Ion in an Ultracold Buffer Gas.
AB  - An ion in a radio frequency ion trap interacting with a buffer gas of ultracold
      neutral atoms is a driven dynamical system which has been found to develop a
      nonthermal energy distribution with a power law tail. The exact analytical form
      of this distribution is unknown, but has often been represented empirically by q
      exponential (Tsallis) functions. Based on the concepts of superstatistics, we
      introduce a framework for the statistical mechanics of an ion trapped in an rf
      field subject to collisions with a buffer gas. We derive analytic ion secular
      energy distributions from first principles both neglecting and including the
      effects of the thermal energy of the buffer gas. For a buffer gas with a finite
      temperature, we prove that Tsallis statistics emerges from the combination of a
      constant heating term and multiplicative energy fluctuations. We show that the
      resulting distributions essentially depend on experimentally controllable
      parameters paving the way for an accurate control of the statistical properties
      of ion-atom hybrid systems.

PMID- 28430496
TI  - Renormalized Stress-Energy Tensor of an Evaporating Spinning Black Hole.
AB  - We provide the first calculation of the renormalized stress-energy tensor (RSET)
      of a quantum field in Kerr spacetime (describing a stationary spinning black
      hole). More specifically, we employ a recently developed mode-sum regularization
      method to compute the RSET of a minimally coupled massless scalar field in the
      Unruh vacuum state, the quantum state corresponding to an evaporating black hole.
      The computation is done here for the case a=0.7M, using two different variants of
      the method: t splitting and phi splitting, yielding good agreement between the
      two (in the domain where both are applicable). We briefly discuss possible
      implications of the results for computing semiclassical corrections to certain
      quantities, and also for simulating dynamical evaporation of a spinning black
      hole.

PMID- 28430497
TI  - Observation of Thermal Equilibrium in Capillary Wave Turbulence.
AB  - We investigate capillary wave turbulence at scales larger than the forcing one.
      At such scales, our measurements show that the surface waves dynamics is the one
      of a thermal equilibrium state in which the effective temperature is related to
      the injected power. We characterize this evolution with a scaling law and report
      the statistical properties of the large-scale surface elevation depending on this
      effective temperature.

PMID- 28430498
TI  - Interfacial Dzyaloshinskii-Moriya Interaction in Pt/CoFeB Films: Effect of the
      Heavy-Metal Thickness.
AB  - We report the observation of a Pt layer thickness dependence on the induced
      interfacial Dzyaloshinskii-Moriya interaction in ultrathin Pt(d_{Pt})/CoFeB
      films. Taking advantage of the large spin-orbit coupling of the heavy metal, the
      interfacial Dzyaloshinskii-Moriya interaction is quantified by Brillouin light
      scattering measurements of the frequency nonreciprocity of spin waves in the
      ferromagnet. The magnitude of the induced Dzyaloshinskii-Moriya coupling is found
      to saturate to a value of 0.45  mJ/m^{2} for Pt thicknesses larger than ~2  nm.
      The experimental results are explained by analytical calculations based on the
      three-site indirect exchange mechanism that predicts a Dzyaloshinskii-Moriya
      interaction at the interface between a ferromagnetic thin layer and a heavy
      metal. Our findings open up a way to control and optimize chiral effects in
      ferromagnetic thin films through the thickness of the heavy-metal layer.

PMID- 28430499
TI  - BC8 Silicon (Si-III) is a Narrow-Gap Semiconductor.
AB  - Large-volume, phase-pure synthesis of BC8 silicon (Ia3[over -], cI16) has enabled
      bulk measurements of optical, electronic, and thermal properties. Unlike previous
      reports that conclude BC8-Si is semimetallic, we demonstrate that this phase is a
      direct band gap semiconductor with a very small energy gap and moderate carrier
      concentration and mobility at room temperature, based on far- and midinfrared
      optical spectroscopy, temperature-dependent electrical conductivity, Seebeck and
      heat capacity measurements. Samples exhibit a plasma wavelength near 11  MUm,
      indicating potential for infrared plasmonic applications. Thermal conductivity is
      reduced by 1-2 orders of magnitude depending on temperature as compared with the
      diamond cubic (DC-Si) phase. The electronic structure and dielectric properties
      can be reproduced by first-principles calculations with hybrid functionals after
      adjusting the level of exact Hartree-Fock (HF) exchange mixing. These results
      clarify existing limited and controversial experimental data sets and ab initio
      calculations.

PMID- 28430500
TI  - Thermalization and Return to Equilibrium on Finite Quantum Lattice Systems.
AB  - Thermal states are the bedrock of statistical physics. Nevertheless, when and how
      they actually arise in closed quantum systems is not fully understood. We
      consider this question for systems with local Hamiltonians on finite quantum
      lattices. In a first step, we show that states with exponentially decaying
      correlations equilibrate after a quantum quench. Then, we show that the
      equilibrium state is locally equivalent to a thermal state, provided that the
      free energy of the equilibrium state is sufficiently small and the thermal state
      has exponentially decaying correlations. As an application, we look at a related
      important question: When are thermal states stable against noise? In other words,
      if we locally disturb a closed quantum system in a thermal state, will it return
      to thermal equilibrium? We rigorously show that this occurs when the correlations
      in the thermal state are exponentially decaying. All our results come with finite
      size bounds, which are crucial for the growing field of quantum thermodynamics
      and other physical applications.

PMID- 28430501
TI  - Metric Independence of Vacuum and Force-Free Electromagnetic Fields.
AB  - Electromagnetic fields which solve the vacuum Maxwell equations in one spacetime
      are well known to also be solutions in all spacetimes with conformally related
      metrics. This provides a sense in which electromagnetism alone cannot be used to
      measure certain aspects of geometry. We show that there is actually much more
      which cannot be so measured; relatively little of a spacetime's geometry is in
      fact imprinted in any particular electromagnetic field. This is demonstrated by
      finding a much larger class of metric transformations-involving five free
      functions-which preserve Maxwell solutions both in vacuum, without local
      currents, and also for the force-free electrodynamics associated with a tenuous
      plasma. One consequence of this is that many of the exact force-free fields which
      have previously been found around Schwarzschild and Kerr black holes are also
      solutions in appropriately identified flat backgrounds. As a more direct
      application, we use our metric transformations to write down a large class of
      electromagnetic waves which remain unchanged by a large class of gravitational
      waves propagating "in the same direction."

PMID- 28430502
TI  - Majorana Zero Modes Protected by a Hopf Invariant in Topologically Trivial
      Superconductors.
AB  - Majorana zero modes are usually attributed to topological superconductors. We
      study a class of two-dimensional topologically trivial superconductors without
      chiral edge modes, which nevertheless host robust Majorana zero modes in
      topological defects. The construction of this minimal single-band model is
      facilitated by the Hopf map and the Hopf invariant. This work will stimulate
      investigations of Majorana zero modes in superconductors in the topologically
      trivial regime.

PMID- 28430503
TI  - Fate of Majorana Modes in CeCoIn_{5}/YbCoIn_{5} Superlattices: A Test Bed for the
      Reduction of Topological Classification.
AB  - In this paper, we propose CeCoIn_{5}/YbCoIn_{5} superlattice systems as a test
      bed for the reduction of topological classification in free fermions. We find
      that the system with a quadlayer of CeCoIn_{5} shows a topological crystalline
      superconducting phase with the mirror Chern number eight at the noninteracting
      level. Furthermore, we demonstrate that in the presence of two-body interactions,
      gapless edge modes are no longer protected by the symmetry in the system with a
      quadlayer, but are protected in the system with a bilayer or trilayer. This
      clearly exemplifies the reduction of topological classification from Z?Z to
      Z?Z_{8}.

PMID- 28430504
TI  - Topological Exciton Bands in Moire Heterojunctions.
AB  - Moire patterns are common in van der Waals heterostructures and can be used to
      apply periodic potentials to elementary excitations. We show that the optical
      absorption spectrum of transition metal dichalcogenide bilayers is profoundly
      altered by long period moire patterns that introduce twist-angle dependent
      satellite excitonic peaks. Topological exciton bands with nonzero Chern numbers
      that support chiral excitonic edge states can be engineered by combining three
      ingredients: (i) the valley Berry phase induced by electron-hole exchange
      interactions, (ii) the moire potential, and (iii) the valley Zeeman field.

PMID- 28430505
TI  - Excitation-Gap Scaling near Quantum Critical Three-Dimensional Antiferromagnets.
AB  - By means of large-scale quantum Monte Carlo simulations, we examine the quantum
      critical scaling of the magnetic excitation gap (the triplon gap) in a three
      dimensional dimerized quantum antiferromagnet, the bicubic lattice, and identify
      characteristic multiplicative logarithmic scaling corrections atop the leading
      mean-field behavior. These findings are in accord with field-theoretical
      predictions that are based on an effective description of the quantum critical
      system in terms of an asymptotically free field theory, which exhibits a
      logarithmic decay of the renormalized interaction strength upon approaching the
      quantum critical point. Furthermore, using bond-based singlet spectroscopy, we
      identify the amplitude (Higgs) mode resonance within the antiferromagnetic
      region. We find a Higgs mass scaling in accord with field-theoretical predictions
      that relate it by a factor of sqrt[2] to the corresponding triplon gap in the
      quantum disordered regime. In contrast to the situation in lower-dimensional
      systems, we observe in this three-dimensional coupled-dimer system a distinct
      signal from the amplitude mode also in the dynamical spin structure factor. Its
      width is observed to vanish proportional to the Higgs mass in the accessible
      proximity to the quantum critical point.

PMID- 28430506
TI  - Demonstration of Multisetting One-Way Einstein-Podolsky-Rosen Steering in Two
      Qubit Systems.
AB  - Einstein-Podolsky-Rosen (EPR) steering describes the ability of one party to
      remotely affect another's state through local measurements. One of the most
      distinguishable properties of EPR steering is its asymmetric aspect. Steering can
      work in one direction but fail in the opposite direction. This type of one-way
      steering, which is different from the symmetry concepts of entanglement and Bell
      nonlocality, has garnered much interest. However, an experimental demonstration
      of genuine one-way EPR steering in the simplest scenario, i.e., one that employs
      two-qubit systems, is still lacking. In this Letter, we experimentally
      demonstrate one-way EPR steering with multimeasurement settings for a class of
      two-qubit states, which are still one-way steerable even with infinite settings.
      The steerability is quantified by the steering radius, which represents a
      necessary and sufficient steering criterion. The demonstrated one-way steering in
      the simplest bipartite quantum system is of fundamental interest and may provide
      potential applications in one-way quantum information tasks.

PMID- 28430507
TI  - Beating the Standard Sensitivity-Bandwidth Limit of Cavity-Enhanced
      Interferometers with Internal Squeezed-Light Generation.
AB  - The shot-noise limited peak sensitivity of cavity-enhanced interferometric
      measurement devices, such as gravitational-wave detectors, can be improved by
      increasing the cavity finesse, even when comparing fixed intracavity light
      powers. For a fixed light power inside the detector, this comes at the price of a
      proportional reduction in the detection bandwidth. High sensitivity over a large
      span of signal frequencies, however, is essential for astronomical observations.
      It is possible to overcome this standard sensitivity-bandwidth limit using
      nonclassical correlations in the light field. Here, we investigate the internal
      squeezing approach, where the parametric amplification process creates a
      nonclassical correlation directly inside the interferometer cavity. We
      theoretically analyze the limits of the approach and measure 36% increase in the
      sensitivity-bandwidth product compared to the classical case. To our knowledge,
      this is the first experimental demonstration of an improvement in the sensitivity
      bandwidth product using internal squeezing, opening the way for a new class of
      optomechanical force sensing devices.

PMID- 28430509
TI  - Erratum: Bose-Einstein Condensation of Long-Lifetime Polaritons in Thermal
      Equilibrium [Phys. Rev. Lett. 118, 016602 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.016602.

PMID- 28430510
TI  - Topologically Allowed Nonsixfold Vortices in a Sixfold Multiferroic Material:
      Observation and Classification.
AB  - We report structural transformation of sixfold vortex domains into two-, four-,
      and eightfold vortices via a different type of topological defect in hexagonal
      manganites. Combining high-resolution electron microscopy and Landau-theory-based
      numerical simulations, we investigate the remarkable atomic arrangement and the
      intertwined relationship between the vortex structures and the topological
      defects. The roles of their displacement field, formation temperature, and
      nucleation sites are revealed. All conceivable vortices in the system are
      topologically classified using homotopy group theory, and their origins are
      identified.

PMID- 28430511
TI  - Anti-de Sitter Particles and Manifest (Super)Isometries.
AB  - Starting from the classical action for a spin-zero particle in a D-dimensional
      anti-de Sitter (AdS) spacetime, we recover the Breitenlohner-Freedman bound by
      quantization. For D=4, 5, 7 and using an Sl(2;K) spinor notation for K=R,C,H, we
      find a bitwistor form of the action for which the AdS isometry group is linearly
      realized, although only for zero mass when D=4, 7 in agreement with previous
      constructions. For zero mass and D=4 the conformal isometry group is linearly
      realized. We extend these results to the superparticle in the maximally
      supersymmetric "AdS*S" string or M-theory vacua, showing that quantization yields
      a 128+128 component supermultiplet. We also extend them to the null string.

PMID- 28430512
TI  - Simplifying Differential Equations for Multiscale Feynman Integrals beyond
      Multiple Polylogarithms.
AB  - In this Letter we exploit factorization properties of Picard-Fuchs operators to
      decouple differential equations for multiscale Feynman integrals. The algorithm
      reduces the differential equations to blocks of the size of the order of the
      irreducible factors of the Picard-Fuchs operator. As a side product, our method
      can be used to easily convert the differential equations for Feynman integrals
      which evaluate to multiple polylogarithms to an epsilon form.

PMID- 28430513
TI  - Inelastic Neutrino-Nucleus Interactions within the Spectral Function Formalism.
AB  - We report the results of a study of neutrino-carbon interactions at beam energies
      ranging between a few hundred MeV's and a few tens of GeVs carried out within the
      framework of the impulse approximation using a realistic spectral function. The
      contributions of quasielastic scattering, resonance production, and deep
      inelastic scattering-consistently obtained, for the first time, from a model
      based on a realistic description of the nuclear ground state-are compared and
      analyzed.

PMID- 28430514
TI  - Essential Conditions for Dynamic Interference.
AB  - We develop general quantitative criteria for dynamic interference, a
      manifestation of a double-slit interference in time which should be realizable
      with brilliant state-of-the-art high-frequency laser sources. Our analysis
      reveals that the observation of dynamic interference hinges upon maximizing the
      difference between the dynamic polarization of the initial bound and the final
      continuum states of the electron during the light pulse while keeping depletion
      of the initial state small. These two properties, Stark shift and depletion, can
      be determined from electronic structure calculations avoiding expensive
      propagation in time. Confirmed by numerical results, we predict that this is
      impossible for the hydrogen ground state but feasible for excited states; this
      has been exemplified for the case of the hydrogen 2p state.

PMID- 28430515
TI  - Scattering Theory on Surface Majorana Fermions by an Impurity in ^{3}He-B.
AB  - We have formulated the scattering theory on Majorana fermions emerging in the
      surface bound state of the superfluid ^{3}He B phase (^{3}He-B) by an impurity.
      By applying the theory to the electron bubble, which is regarded as the impurity,
      trapped below a free surface of ^{3}He-B, the observed mobility of the electron
      bubble [J. Phys. Soc. Jpn. 82, 124607 (2013)JUPSAU0031
      901510.7566/JPSJ.82.124607] is quantitatively reproduced. The mobility is
      suppressed in low temperatures from the expected value in the bulk ^{3}He-B by
      the contribution from the surface Majorana fermions. By contrast, the mobility
      does not depend on the trapped depth of the electron bubble in spite of the
      spatial variation of the wave function of the surface Majorana fermions. Our
      formulated theory demonstrates the depth-independent mobility by considering
      intermediate states in the scattering process. Therefore, we conclude that the
      experiment has succeeded in observing Majorana fermions in the surface bound
      state.

PMID- 28430516
TI  - Strong Constraints on Self-Interacting Dark Matter with Light Mediators.
AB  - Coupling dark matter to light new particles is an attractive way to combine
      thermal production with strong velocity-dependent self-interactions. Here we
      point out that in such models the dark matter annihilation rate is generically
      enhanced by the Sommerfeld effect, and we derive the resulting constraints from
      the cosmic microwave background and other indirect detection probes. For the
      frequently studied case of s-wave annihilation, these constraints exclude the
      entire parameter space where the self-interactions are large enough to address
      the small-scale problems of structure formation.

PMID- 28430517
TI  - Small Particle Driven Chain Disentanglements in Polymer Nanocomposites.
AB  - Using neutron spin-echo spectroscopy, x-ray photon correlation spectroscopy, and
      bulk rheology, we studied the effect of particle size on the single-chain
      dynamics, particle mobility, and bulk viscosity in athermal polyethylene oxide
      gold nanoparticle composites. The results reveal a ~25% increase in the reptation
      tube diameter with the addition of nanoparticles smaller than the entanglement
      mesh size (~5  nm), at a volume fraction of 20%. The tube diameter remains
      unchanged in the composite with larger (20 nm) nanoparticles at the same loading.
      In both cases, the Rouse dynamics is insensitive to particle size. These results
      provide a direct experimental observation of particle-size-driven
      disentanglements that can cause non-Einstein-like viscosity trends often observed
      in polymer nanocomposites.

PMID- 28430518
TI  - Tunable Sign Change of Spin Hall Magnetoresistance in Pt/NiO/YIG Structures.
AB  - Spin Hall magnetoresistance (SMR) has been investigated in Pt/NiO/YIG structures
      in a wide range of temperature and NiO thickness. The SMR shows a negative sign
      below a temperature that increases with the NiO thickness. This is contrary to a
      conventional SMR theory picture applied to the Pt/YIG bilayer, which always
      predicts a positive SMR. The negative SMR is found to persist even when NiO
      blocks the spin transmission between Pt and YIG, indicating it is governed by the
      spin current response of the NiO layer. We explain the negative SMR by the NiO
      "spin flop" coupled with YIG, which can be overridden at higher temperature by
      positive SMR contribution from YIG. This highlights the role of magnetic
      structure in antiferromagnets for transport of pure spin current in multilayers.

PMID- 28430519
TI  - Energy-Resolved Ultrashort Delays of Photoelectron Emission Clocked by Orthogonal
      Two-Color Laser Fields.
AB  - A phase-controlled orthogonal two-color (OTC) femtosecond laser pulse is employed
      to probe the time delay of photoelectron emission in the strong-field ionization
      of atoms. The OTC field spatiotemporally steers the emission dynamics of the
      photoelectrons and meanwhile allows us to unambiguously distinguish the main and
      sideband peaks of the above-threshold ionization spectrum. The relative phase
      shift between the main and sideband peaks, retrieved from the phase-of-phase of
      the photoelectron spectrum as a function of the laser phase, gradually decreases
      with increasing electron energy, and becomes zero for the fast electron which is
      mainly produced by the rescattering process. Furthermore, a Freeman resonance
      delay of 140+/-40 attoseconds between photoelectrons emitted via the 4f and 5p
      Rydberg states of argon is observed.

PMID- 28430520
TI  - Wind Generated Rogue Waves in an Annular Wave Flume.
AB  - We investigate experimentally the statistical properties of a wind-generated wave
      field and the spontaneous formation of rogue waves in an annular flume. Unlike
      many experiments on rogue waves where waves are mechanically generated, here the
      wave field is forced naturally by wind as it is in the ocean. What is unique
      about the present experiment is that the annular geometry of the tank makes waves
      propagating circularly in an unlimited-fetch condition. Within this peculiar
      framework, we discuss the temporal evolution of the statistical properties of the
      surface elevation. We show that rogue waves and heavy-tail statistics may develop
      naturally during the growth of the waves just before the wave height reaches a
      stationary condition. Our results shed new light on the formation of rogue waves
      in a natural environment.

PMID- 28430521
TI  - Perinatal light imprinting of circadian clocks and systems (PLICCS): A signature
      of photoperiod around birth on circadian system stability and association with
      cancer.
AB  - Recent findings from animal models suggest that plasticity of human circadian
      clocks and systems may be differentially affected by different paradigms of
      perinatal photoperiod exposure to the detriment of health in later life,
      including cancer development. Focusing on the example of cancer, we carry out a
      series of systematic literature reviews concerning perinatal light imprinting of
      circadian clocks and systems (PLICCS) in animal models, and concerning the risk
      of cancer development with the primary determinants of the perinatal photoperiod,
      namely season of birth or latitude of birth. The results from these systematic
      reviews provide supporting evidence of the PLICCS and cancer rationale and
      highlight that investigations of PLICCS in humans are warranted. Overall, we
      discuss findings from experimental research and insights from epidemiological
      studies. Considerations as to how to "test" PLICCS in epidemiological studies and
      as to the potential for non-invasive preventative measures during perinatal
      periods close our synthesis. If the PLICCS rationale holds true, it opens the
      exciting prospect for amenable, early-life, preventative measures against cancer
      development (and other disorders) in later life. Indeed, non-invasive
      anthropogenic light exposure may have enormous potential to alleviate the public
      health and economic burden of circadian-related diseases.

PMID- 28430522
TI  - Impact of naturalistic lighting on hospitalized stroke patients in a
      rehabilitation unit: Design and measurement.
AB  - INTRODUCTION AND RATIONALE: Stroke is a major cause of acquired cerebral
      disability among adults, frequently accompanied by depression, anxiety, cognitive
      impairment, disrupted sleep and fatigue. New ways of intervention to prevent
      these complications are therefore needed. The major circadian regulator, the
      suprachiasmatic nucleus, is mainly controlled by natural daylight, and the blue
      spectrum is considered the most powerful. During stroke rehabilitation, patients
      typically are mostly indoors and therefore not exposed to the natural daytime
      variation in light intensity. Furthermore, several rehabilitation hospitals may
      be exposed to powerful light in the blue spectrum, but at a time that is
      adversely related to their endogenous circadian phase, for example in the late
      evening instead of the daytime. HYPOTHESIS: Naturalistic light that mimics the
      natural daytime spectrum variation will have a positive impact on the health of
      poststroke patients admitted to rehabilitation. We test specifically for improved
      sleep and less fatigue (questionnaires, polysomnography, Actiwatch), improved
      well-being (questionnaires), lessen anxiety and depression (questionnaires),
      improved cognition (tests), stabilizing of the autonomous nervous system (ECG/HR,
      blood pressure, temperature) and stabilizing of the diurnal biochemistry (blood
      markers). STUDY DESIGN: The study is a prospective parallel longitudinal
      randomized controlled study (quasi randomization). Stroke patients in need of
      rehabilitation will be included at the acute stroke unit and randomized to either
      the intervention unit (naturalistic lighting) or the control unit (CU) (standard
      lighting). The naturalistic light is installed in the entire IU (Cromaviso,
      Denmark). CONCLUSION: This study aims to elucidate the influence of naturalistic
      light on patients during long-term hospitalization in a real hospital setting.
      The hypotheses are based on preclinical research, as studies using naturalistic
      light have never been performed before. Investigating the effects of naturalistic
      light in a clinical setting is therefore much needed.

PMID- 28430523
TI  - Altered Expression of miRNAs Is Related to Larynx Cancer TNM Stage and Patients'
      Smoking Status.
AB  - It has been reported that microRNAs (miRNAs) are responsible for acquiring all
      the hallmarks of cancer cells, as well as have a significant impact on the
      clinical management of cancers at every stage, including prognosis, remission,
      relapse, and metastasis. In this study, we investigated the association of miR
      29a-3p, miR-202-3p, miR-3713, miR-4768-3p, and miR-548aa expression with
      clinicopathologic features in patients suffering from laryngeal cancer (LC) and
      determined the potential role of studied miRNAs in the progression of LC. The
      study group consisted of 48 patients with untreated primary tumors of head and
      neck cancer localized in the larynx. Expression of the selected miRNAs was
      verified by the qRT-PCR technique. We showed that the expression of miR-29a as
      well as miR-548aa was positively correlated with tumor stage and lymph node
      metastasis, whereas the expression of miR-4768-3p was negatively correlated with
      lymph node metastasis. Furthermore, we investigated that exposure to cigarette
      smoke altered miRNA expression profile in LC. The expression level of miR-202-3p
      was significantly increased in smoking patients compared with nonsmokers, whereas
      the miR-4768-3p, miR-548aa, and miR-3713 were markedly decreased. Our research
      contributed toward better elucidating the mechanisms underlying the progression
      of LC as well as the use of miRNAs inhibitors as novel agents against progression
      and metastasis of LC.

PMID- 28430524
TI  - miRNA-Related Polymorphisms in miR-423 (rs6505162) and PEX6 (rs1129186) and Risk
      of Esophageal Squamous Cell Carcinoma in an Iranian Cohort.
AB  - AIMS: Iran is located in the Asian esophageal cancer belt. It is a high-risk
      region for esophageal squamous cell carcinoma (ESCC). The extent to which genetic
      components, especially variants within miRNAs or their binding sites, contribute
      to risk of ESCC in the region is not yet fully understood. Herein, tests were
      done on an Iranian cohort to evaluate the association of miRNA-related
      polymorphisms in miR-423 (rs6505162) and peroxisomal biogenesis factor 6 (PEX6)
      (rs1129186 within a miR-149-5p-binding site) with the risk of ESCC risk. METHODS:
      This study recruited 200 ESCC patients and 300 healthy individuals. Genotyping
      was performed using the polymerase chain reaction-restriction fragment length
      polymorphism method. Target genes and biological processes that are regulated by
      miR-423 and may be affected by a change in miR-423 expression were identified by
      in silico analysis. RESULTS: Logistic regression analyses revealed an association
      between rs6505162 and ESCC, assuming codominant (AA vs. CC, odds ratios, OR [95%
      confidence interval, CI]: 0.32 [0.15-0.69], p-value: 0.0076), recessive (AA vs.
      CC+CA, OR [95% CI]: 0.35 [0.16-0.73], p-value: 0.0027), and log-additive models
      (OR [95% CI]: 0.69 [0.52-0.91], p-value: 0.0084). No significant association was
      observed for PEX6 rs1129186. In silico analyses revealed several genes and
      biological processes that are regulated by miR-423 in ESCC. CONCLUSION: This
      study identified the first evidence of an association of a miRNA-related variant
      with risk of ESCC in an Iranian cohort. PEX6 rs1129186 may not modulate the risk
      of ESCC in the cohort.

PMID- 28430525
TI  - Differential Expression of miR-202 and Validation of Predicted Target Genes in
      the Skin Tissue of C57BL/6 Black Mice and BALB/c White Mice.
AB  - In recent years, with the need of the fur industry to obtain greater quantities
      of high-quality fur and the research of hair follicle development attracting
      greater attention, the role of miRNAs in hair follicle development has become a
      field of intense interest. miRNAs are short length RNAs that affect gene
      regulation by binding to the 3'-untranslated region (3'UTR) of the mRNAs of
      certain target genes. This study predicted and validated the target genes of miR
      202 in the skin tissue of C57BL/6 black mice and BALB/c white mice. The
      expression of miR-202 target genes (wnt5a, kit, and tcf7) was examined by real
      time quantitative polymerase chain reaction and western blot in the mouse skin
      tissue and human embryonic kidney 293T cells (HEK293T cells) which overexpress
      miR-202. The luciferase reporter gene system was used to verify the correlation
      between the expression of miR-202 and its putative target genes. We show that the
      expression of miR-202 was higher in the skin tissue of C57BL/6 black mice than in
      the skin tissue of BALB/c white mice (p < 0.05). Furthermore, the expression of
      wnt5a, kit, and tcf7 was observed to be negatively correlated with the expression
      of miR-202 and to be downregulated by miR-202 in vitro and in vivo. The
      luciferase reporter gene system indicated that the target sequences of miR-202
      are present in 3'UTR of wnt5a, kit, and tcf7 mRNAs. Altogether, this study has
      shown that the expression of miR-202 was different in the skin tissue of C57BL/6
      black mice and BALB/c white mice and that wnt5a, kit, and tcf7 are negatively
      regulated by miR-202.

PMID- 28430526
TI  - The Bow Tie Shape of the Anterior Cruciate Ligament as Visualized by High
      Resolution Magnetic Resonance Imaging.
AB  - BACKGROUND: Although numerous studies have examined the anatomic characteristics
      of the anterior cruciate ligament (ACL), its actual shape remains unclear.
      PURPOSE: To determine the average shape of the ACL by analyzing its cross section
      through the use of high-resolution magnetic resonance imaging (MRI) data. STUDY
      DESIGN: Descriptive laboratory study. METHODS: The study included 96 MRIs,
      conducted using a 3.0-T magnet, to analyze the shape of the ACL. Three
      dimensional, curved multiplanar reconstruction was used to obtain cross sections
      at 7 points (femoral insertion; midsubstance 1, 2, 3, 4, and 5 from the femoral
      side to the tibial side; and tibial insertion). The width and thickness of cross
      sections were measured by 2 independent observers, and the ratio of width to
      thickness was calculated to determine the proportions of each cross section. The
      7 cross sections were accumulated and standardized to generate an average model
      through the use of image analysis software developed by the authors. RESULTS: The
      mean +/- SD width (femoral insertion, 17.02 +/- 2.17 mm; tibial insertion, 17.33
      +/- 2.03 mm) and thickness (femoral insertion, 11.03 +/- 1.75 mm; tibial
      insertion, 10.09 +/- 1.70 mm) of both insertions were significantly larger than
      those of midsubstance 4 (width, 9.99 +/- 1.87 mm; thickness, 6.53 +/- 1.25 mm) (
      P < .001). The mean ratios of width to thickness of the 7 cross sections from
      femoral insertion to tibial insertion were 1.57 +/- 0.23, 3.36 +/- 0.57, 3.07 +/-
      0.81, 2.18 +/- 0.54, 1.56 +/- 0.32, 2.16 +/- 0.48, and 1.75 +/- 0.28,
      respectively. The shape of the cross section at midsubstance 4 was an oval
      isthmus, which was the most narrow and well-balanced shape. It was transformed
      into a wide band at midsubstance 1 and 5. The shape of the femoral insertion was
      semicircular, with its anterior side slightly straight and its posterior side
      convex. The tibial insertion was kidney bean-shaped. CONCLUSION: On 3.0-T MRI,
      the ACL has a "bow tie" shape, including an oval isthmus, with a semicircular
      femoral insertion and kidney bean-shaped tibial insertion. CLINICAL RELEVANCE:
      The measurement method will allow surgeons to quantitatively diagnose partial
      injuries of the ACL using a noninvasive system in actual patients.

PMID- 28430527
TI  - HERC4 Is Overexpressed in Hepatocellular Carcinoma and Contributes to the
      Proliferation and Migration of Hepatocellular Carcinoma Cells.
AB  - Recently, more and more evidences unveiled that ubiquitin-proteasome system (UPS)
      makes an important contribution to the occurrence and development of cancer.
      HERC4 is one identified Ubiqutin ligase E3, a member of UPS. Although some
      studies showed that HERC4 abnormally expresses in many cancer cells, till now,
      nothing has been reported about the function of HERC4 in the development of
      hepatoma carcinoma. To this end, in this study, we studied the function of HERC4
      for the first time in hepatoma carcinoma cells. We detected the expression of
      HERC4 in tumor and normal tissues, and in hepatoma carcinoma cell lines by using
      qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence. The data
      showed that tumor tissues expressed higher HERC4 than normal ones. HERC4 was
      expressed, although to a different extent, in hepatoma carcinoma cell lines.
      Colony formation assay, CCK-8 assay, EdU assay, wound healing assay, and FACS
      indicated that HERC4 plays a role in cell proliferative and migration ability.
      HERC4 overexpression increases the proliferative and migration ability and
      reduces apoptosis of hepatoma carcinoma cells; in contrast, knockdown of HERC4
      decreases the proliferative and migration ability and increases the apoptosis
      rate of hepatoma carcinoma cells. Taken together, our findings showed that HERC4
      has an effect on the occurrence and development of hepatoma carcinoma by
      promoting hepatoma carcinoma cell proliferation and migration, and by reducing
      cell apoptosis, further providing another therapeutic target for the intervention
      of related diseases.

PMID- 28430528
TI  - ECOG-ACRIN 1308: Commentary on a Negative Phase II Trial.

PMID- 28430529
TI  - Purpose of Induction Chemotherapy in E1308 and Importance of Patient-Reported
      Outcomes in Deintensification Trials.

PMID- 28430530
TI  - Reply to A. Garden et al.

PMID- 28430531
TI  - Phonological development of Danish-speaking children: A normative cross-sectional
      study.
AB  - Detailed knowledge about speech development in children acquiring different
      languages provides important information from a clinical and a theoretical
      perspective: First, it provides a baseline for the evaluation of whether a child
      shows typical, delayed or deviant speech development. Further, differences in
      speech development across languages can help to understand how the phonological
      systems of ambient languages affects children's speech acquisition. To date,
      little is known about Danish. It was suggested, however, that the acquisition
      process might be slower for Danish-speaking children due to the "blurry" sound
      structure of Danish. The aim of the current study was, therefore, to investigate
      typical speech development in 443 Danish-speaking children, i.e. types and age of
      occurrence of children's phonological processes as well as on the acquisition of
      phones and clusters. The results showed that Danish-speaking children, in
      contrast to the expectations, were not delayed but advanced compared to children
      acquiring other languages.

PMID- 28430532
TI  - Overcoming discourse-linking difficulties in aphasia: The case of clitic
      pronouns.
AB  - The present study aims to contribute to the ongoing discussion about the impact
      of discourse-linking deficits on the performance of individuals with aphasia by
      providing new data from a set of rarely investigated constructions: sentences in
      which a clitic pronoun coexists alongside with the full DP it agrees with. To do
      so, we use data of individuals with non-fluent aphasias who need to overcome the
      difficulties in direct object (accusative) clitic production. This results in
      overproduction of non-target clitic right dislocations (RDs) and clitic doubling
      (CD). Data from 15 individual's native speakers of Spanish and Catalan are
      discussed. Data complement the results of previous investigations on discourse
      linking effects in these languages, allowing the interpretation of results across
      constructions.

PMID- 28430533
TI  - New directions in the rational design of electrical and magnetic seizure
      therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic
      Seizure Therapy (MST).
AB  - Electroconvulsive therapy remains a key treatment option for severe cases of
      depression, but undesirable side-effects continue to limit its use. Innovations
      in the design of novel seizure therapies seek to improve its risk benefit ratio
      through enhanced control of the focality of stimulation. The design of seizure
      therapies with increased spatial precision is motivated by avoiding stimulation
      of deep brain structures implicated in memory retention, including the
      hippocampus. The development of two innovations in seizure therapy-individualized
      low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are
      detailed. iLAST is a method of seizure titration involving reducing current
      spread in the brain by titrating current amplitude from the traditional fixed
      amplitudes. MST, which can be used in conjunction with iLAST dosing methods,
      involves the use of magnetic stimulation to reduce shunting and spreading of
      current by the scalp occurring during electrical stimulation. Evidence is
      presented on the rationale for increasing the focality of ECT in hopes of
      preserving its effectiveness, while reducing cognitive side-effects. Finally, the
      value of electric field and neural modelling is illustrated to explain observed
      clinical effects of modifications to ECT technique, and their utility in the
      rational design of the next generation of seizure therapies.

PMID- 28430534
TI  - Chronobiological factors for compassion satisfaction and fatigue among ambulatory
      oncology caregivers.
AB  - Primary caregivers for victims of chronic illness and or trauma experience both
      positive and negative emotional consequences. These are broadly classified as
      compassion satisfaction (CS) and compassion fatigue (CF). Because one of the
      components of CF, burnout, varies with chronotype and sleep quality, we assessed
      the influence of chronobiological features on the broader constructs of CS and
      CF. Responses from primary ambulatory care oncology staff working dayshifts were
      assessed for potential relationships of chronotype and sleep quality with CS and
      CF using the professional quality of life scale. These were analyzed further in a
      multivariate model that included personality and job satisfaction as cofactors.
      We found that sleep quality was a key contributor to CS development and CF
      reduction. Morningness was positively linked to CS, but the univariate
      association was masked in the multivariate model. Job satisfaction (contingent
      rewards, nature of work and operating procedures) heavily influenced CS and CF
      development. Agreeableness and openness showed positive correlations with CS and
      negative with burnout, while emotional stability was linked to reduced CF. While
      job satisfaction and personality predictably played roles in the development of
      CS and CF, sleep quality and chronotype contributed significantly to benefits and
      negative consequences of providing care.

PMID- 28430535
TI  - Transcranial focused ultrasound: a new tool for non-invasive neuromodulation.
AB  - Ultrasound (US) is widely known for its utility as a biomedical imaging modality.
      An abundance of evidence has recently accumulated showing that US is also useful
      for non-invasively modulating brain circuit activity. Through a series of studies
      discussed in this short review, it has recently become recognized that
      transcranial focused ultrasound can exert mechanical (non-thermal) bioeffects on
      neurons and cells to produce focal changes in the activity of brain circuits. In
      addition to highlighting scientific breakthroughs and observations that have
      driven the development of the field of ultrasonic neuromodulation, this study
      also provides a discussion of mechanisms of action underlying the ability of
      ultrasound to physically stimulate and modulate brain circuit activity.
      Exemplifying some forward-looking tools that can be developed by integrating
      ultrasonic neuromodulation with other advanced acoustic technologies, some
      innovative acoustic imaging, beam forming, and focusing techniques are briefly
      reviewed. Finally, the future outlook for ultrasonic neuromodulation is
      discussed, specifically in the context of applications employing transcranial
      focused ultrasound for the investigation, diagnosis, and treatment of
      neuropsychiatric disorders.

PMID- 28430537
TI  - If Only We Could See....

PMID- 28430536
TI  - Casting Light on an Occultation in the IAHPC Position Paper on Palliative Care
      and Assisted Dying.

PMID- 28430538
TI  - Biophysical comparison of diphtheria and tetanus toxins with the formaldehyde
      detoxified toxoids, the main components of diphtheria and tetanus vaccines.

PMID- 28430539
TI  - Metabolic pathway rewiring in engineered cyanobacteria for solar-to-chemical and
      solar-to-fuel production from CO2.
AB  - Photoautotrophic cyanobacteria have been developed to convert CO2 to valuable
      chemicals and fuels as solar-to-chemical (S2C) and solar-to-fuel (S2F) platforms.
      Here, I describe the rewiring of the metabolic pathways in cyanobacteria to
      better understand the endogenous carbon flux and to enhance the yield of
      heterologous products. The plasticity of the cyanobacterial metabolism has been
      proposed to be advantageous for the development of S2C and S2F processes. The
      rewiring of the sugar catabolism and of the phosphoketolase pathway in the
      central cyanobacterial metabolism allowed for an enhancement in the level of
      target products by redirecting the carbon fluxes. Thus, metabolic pathway
      rewiring can promote the development of more efficient cyanobacterial cell
      factories for the generation of feasible S2C and S2F platforms.

PMID- 28430540
TI  - Demystifying Orbital Emergencies: A Pictorial Review.
AB  - Imaging of the orbit plays an important role in the workup of orbital
      emergencies. Orbital imaging is particularly useful in the emergency department,
      where clinical history and physical examination may be limited or delayed until
      the exclusion or treatment of more life-threatening conditions. Cross-sectional
      orbital imaging with multidetector computed tomography (CT) and magnetic
      resonance (MR) imaging is commonly performed in addition to ultrasonography. In
      an emergent setting, CT is the preferred modality when evaluating for
      intraorbital foreign bodies, fractures, or calcifications within a mass lesion.
      MR imaging is typically the modality of choice for orbital pathologic conditions,
      owing to its superior ability to delineate the orbital soft tissues and visual
      pathways. CT and MR imaging together may supplement clinical evaluation by
      helping establish an accurate diagnosis, providing an objective assessment of
      disease extent and progression, and assisting in pretreatment planning. Orbital
      emergencies have a spectrum of cross-sectional imaging findings in four major
      categories: infection, trauma, vascular disease, and inflammation. Use of a
      systematic approach to these entities will assist the radiologist with
      identifying immediate threats to vision and thereby facilitate prompt clinical
      management. Familiarity with the clinical presentations also improves the
      radiologist's diagnostic confidence and role in guiding patient care. This
      article reviews imaging protocols, relevant orbital anatomy, the role of CT and
      MR imaging, and key imaging findings of orbital emergencies that the radiologist
      must know. (c) RSNA, 2017.

PMID- 28430542
TI  - ?

PMID- 28430543
TI  - Can "An Extra Layer of Support" Sign Off?

PMID- 28430541
TI  - A Comprehensive Approach to Hepatic Vascular Disease.
AB  - The liver has a complex vascular supply, which involves the inflow of oxygenated
      blood through the hepatic artery (systemic circulation) and deoxygenated blood
      through the portal vein (portal circulation), as well as the outflow of
      deoxygenated blood through the hepatic veins to the inferior vena cava. A
      spectrum of vascular variants can involve the liver. Some of these variants may
      result in areas of enhancement that can mimic more serious pathologic conditions.
      In this article, the authors discuss a spectrum of variants and pathologic
      conditions that may involve the liver vasculature. These include variants,
      anomalies, and diseases involving the portal vein, such as rudimentary portal
      vein, thrombosis, cavernous transformation, thrombotic angiitis,
      thrombophlebitis, transient hepatic attenuation difference or transient hepatic
      intensity difference, portal venous aneurysm, and portal vein gas. The hepatic
      artery can be involved by various diseases, including thrombosis, stenosis, and
      aneurysm or pseudoaneurysm. Unusual "third inflow" sources of venous inflow are
      also discussed, including aberrant right gastric vein, aberrant left gastric
      vein, epigastric-paraumbilical veins, and cholecystic vein. A spectrum of
      variants and diseases involving the inferior vena cava and hepatic veins,
      including thrombosis, Budd-Chiari syndrome, veno-occlusive disease, stenosis,
      torsion, congestive hepatopathy, and peliosis hepatis, are discussed. Vascular
      shunts are illustrated, including portosystemic shunts (intra- and extrahepatic),
      arterioportal shunt, shunts of hereditary hemorrhagic telangiectasia, and
      acquired arteriovenous fistula. Familiarity with the pathogenesis and imaging
      features of these vascular entities can aid radiologic diagnoses and guide
      appropriate patient management. (c)RSNA, 2017.

PMID- 28430544
TI  - Trust and the Compliance-Reliance Paradigm: The Effects of Risk, Error Bias, and
      Reliability on Trust and Dependence.
AB  - OBJECTIVE: This study provides a theoretical link between trust and the
      compliance-reliance paradigm. We propose that for trust mediation to occur, the
      operator must be presented with a salient choice, and there must be an element of
      risk for dependence. BACKGROUND: Research suggests that false alarms and misses
      affect dependence via two independent processes, hypothesized as trust in signals
      and trust in nonsignals. These two trust types manifest in categorically
      different behaviors: compliance and reliance. METHOD: Eighty-eight participants
      completed a primary flight task and a secondary signaling system task.
      Participants evaluated their trust according to the informational bases of trust:
      performance, process, and purpose. Participants were in a high- or low-risk
      group. Signaling systems varied by reliability (90%, 60%) within subjects and
      error bias (false alarm prone, miss prone) between subjects. RESULTS: False-alarm
      rate affected compliance but not reliance. Miss rate affected reliance but not
      compliance. Mediation analyses indicated that trust mediated the relationship
      between false-alarm rate and compliance. Bayesian mediation analyses favored
      evidence indicating trust did not mediate miss rate and reliance. Conditional
      indirect effects indicated that factors of trust mediated the relationship
      between false-alarm rate and compliance (i.e., purpose) and reliance (i.e.,
      process) but only in the high-risk group. CONCLUSION: The compliance-reliance
      paradigm is not the reflection of two types of trust. APPLICATION: This research
      could be used to update training and design recommendations that are based upon
      the assumption that trust causes operator responses regardless of error bias.

PMID- 28430545
TI  - Effects of Motivation: Rewarding Hackers for Undetected Attacks Cause Analysts to
      Perform Poorly.
AB  - OBJECTIVE: The aim of this study was to determine how monetary motivations
      influence decision making of humans performing as security analysts and hackers
      in a cybersecurity game. BACKGROUND: Cyberattacks are increasing at an alarming
      rate. As cyberattacks often cause damage to existing cyber infrastructures, it is
      important to understand how monetary rewards may influence decision making of
      hackers and analysts in the cyber world. Currently, only limited attention has
      been given to this area. METHOD: In an experiment, participants were randomly
      assigned to three between-subjects conditions ( n = 26 for each condition): equal
      payoff, where the magnitude of monetary rewards for hackers and defenders was the
      same; rewarding hacker, where the magnitude of monetary reward for hacker's
      successful attack was 10 times the reward for analyst's successful defense; and
      rewarding analyst, where the magnitude of monetary reward for analyst's
      successful defense was 10 times the reward for hacker's successful attack. In all
      conditions, half of the participants were human hackers playing against Nash
      analysts and half were human analysts playing against Nash hackers. RESULTS:
      Results revealed that monetary rewards for human hackers and analysts caused a
      decrease in attack and defend actions compared with the baseline. Furthermore,
      rewarding human hackers for undetected attacks made analysts deviate
      significantly from their optimal behavior. CONCLUSIONS: If hackers are rewarded
      for their undetected attack actions, then this causes analysts to deviate from
      optimal defend proportions. Thus, analysts need to be trained not become
      overenthusiastic in defending networks. APPLICATION: Applications of our results
      are to networks where the influence of monetary rewards may cause information
      theft and system damage.

PMID- 28430546
TI  - Overall Preference of Running Shoes Can Be Predicted by Suitable Perception
      Factors Using a Multiple Regression Model.
AB  - OBJECTIVE: This study examined (a) the strength of four individual footwear
      perception factors to influence the overall preference of running shoes and (b)
      whether these perception factors satisfied the nonmulticollinear assumption in a
      regression model. BACKGROUND: Running footwear must fulfill multiple functional
      criteria to satisfy its potential users. Footwear perception factors, such as fit
      and cushioning, are commonly used to guide shoe design and development, but it is
      unclear whether running-footwear users are able to differentiate one factor from
      another. METHODS: One hundred casual runners assessed four running shoes on a 15
      cm visual analogue scale for four footwear perception factors (fit, cushioning,
      arch support, and stability) as well as for overall preference during a treadmill
      running protocol. RESULTS: Diagnostic tests showed an absence of
      multicollinearity between factors, where values for tolerance ranged from .36 to
      .72, corresponding to variance inflation factors of 2.8 to 1.4. The multiple
      regression model of these four footwear perception variables accounted for 77.7%
      to 81.6% of variance in overall preference, with each factor explaining a unique
      part of the total variance. CONCLUSION: Casual runners were able to rate each
      footwear perception factor separately, thus assigning each factor a true
      potential to improve overall preference for the users. The results also support
      the use of a multiple regression model of footwear perception factors to predict
      overall running shoe preference. APPLICATION: Regression modeling is a useful
      tool for running-shoe manufacturers to more precisely evaluate how individual
      factors contribute to the subjective assessment of running footwear.

PMID- 28430548
TI  - Correction.

PMID- 28430547
TI  - Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine
      Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund
      Workshop Report.
AB  - The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical
      Education and Research Fund held a workshop to discuss how to leverage the
      anticipated scientific output from the recently launched "Redefining Pulmonary
      Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to
      develop newer approaches to pulmonary vascular disease. PVDOMICS is a
      collaborative, protocol-driven network to analyze all patient populations with
      pulmonary hypertension to define novel pulmonary vascular disease (PVD)
      phenotypes. Stakeholders, including basic, translational, and clinical
      investigators; clinicians; patient advocacy organizations; regulatory agencies;
      and pharmaceutical industry experts, joined to discuss the application of
      precision medicine to PVD clinical trials. Recommendations were generated for
      discussion of research priorities in line with NHLBI Strategic Vision Goals that
      include: (1) A national effort, involving all the stakeholders, should seek to
      coordinate biosamples and biodata from all funded programs to a web-based
      repository so that information can be shared and correlated with other research
      projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary
      Hypertension Breakthrough Initiative, the National Biological Sample and Data
      Repository for PAH, and the National Precision Medicine Initiative. (2) A task
      force to develop a master clinical trials protocol for PVD to apply precision
      medicine principles to future clinical trials. Specific features include: (a)
      adoption of smaller clinical trials that incorporate biomarker-guided enrichment
      strategies, using adaptive and innovative statistical designs; and (b)
      development of newer endpoints that reflect well-defined and clinically
      meaningful changes. (3) Development of updated and systematic variables in
      imaging, hemodynamic, cellular, genomic, and metabolic tests that will help
      precisely identify individual and shared features of PVD and serve as the basis
      of novel phenotypes for therapeutic interventions.

PMID- 28430550
TI  - Round Table on Malignant Hyperthermia in Physically Active Populations: Meeting
      Proceedings.
AB  - CONTEXT:   Recent case reports on malignant hyperthermia (MH)-like syndrome in
      physically active populations indicate potential associations among MH,
      exertional heat stroke (EHS), and exertional rhabdomyolysis (ER). However, an
      expert consensus for clinicians working with these populations is lacking.
      OBJECTIVE:   To provide current expert consensus on the (1) definition of MH; (2)
      history, etiology, and pathophysiology of MH; (3) epidemiology of MH; (4)
      association of MH with EHS and ER; (5) identification of an MH-like syndrome; (6)
      recommendations for acute management of an MH-like syndrome; (7) special
      considerations for physically active populations; and (8) future directions for
      research. SETTING:   An interassociation task force was formed by experts in
      athletic training, exercise science, anesthesiology, and emergency medicine. The
      "Round Table on Malignant Hyperthermia in Physically Active Populations" was
      convened at the University of Connecticut, Storrs, September 17-18, 2015.
      CONCLUSIONS:   Clinicians should consider an MH-like syndrome when a diagnosis of
      EHS or ER cannot be fully explained by clinical signs and symptoms presented by a
      patient or when recurrent episodes of EHS or ER (or both) are unexplained.
      Further research is required to elucidate the genetic and pathophysiological
      links among MH, EHS, and ER.

PMID- 28430555
TI  - Beyond Wires and Seeds: Reflector-guided Breast Lesion Localization and Excision.
AB  - Purpose To evaluate outcomes of Savi Scout (Cianna Medical, Aliso Viejo, Calif)
      reflector-guided localization and excision of breast lesions by analyzing
      reflector placement, localization, and removal, along with target excision and
      rates of repeat excision (referred to as re-excision). Materials and Methods A
      single-institution retrospective review of 100 women who underwent breast lesion
      localization and excision by using the Savi Scout surgical guidance system from
      June 2015 to May 2016 was performed. By using image guidance 0-8 days before
      surgery, 123 nonradioactive, infrared-activated, electromagnetic wave reflectors
      were percutaneously inserted adjacent to or within 111 breast targets. Twenty
      patients had two or three reflectors placed for bracketing or for localizing
      multiple lesions, and when ipsilateral, they were placed as close as 2.6 cm
      apart. Target and reflector were localized intraoperatively by one of two breast
      surgeons who used a handpiece that emitted infrared light and electromagnetic
      waves. Radiographs of the specimen and pathologic analysis helped verify target
      and reflector removal. Target to reflector distance was measured on the mammogram
      and radiograph of the specimen, and reflector depth was measured on the
      mammogram. Pathologic analysis was reviewed. Re-excision rates and complications
      were recorded. By using statistics software, descriptive statistics were
      generated with 95% confidence intervals (CIs) calculated. Results By using
      sonographic (40 of 123; 32.5%; 95% CI: 24.9%, 41.2%) or mammographic (83 of 123;
      67.5%; 95% CI: 58.8% 75.1%) guidance, 123 (100%; 95% CI: 96.4%, 100%) reflectors
      were placed. Mean mammographic target to reflector distance was 0.3 cm. All 123
      (100%; 95% CI: 96.4%, 100%) targets and reflectors were excised. Pathologic
      analysis yielded 54 of 110 malignancies (49.1%; 95% CI: 39.9%, 58.3%; average,
      1.0 cm; range, 0.1-5 cm), 32 high-risk lesions (29.1%; 95% CI: 21.4%, 38.2%), and
      24 benign lesions (21.8%; 95% CI: 115.1%, 30.4%). Four of 54 malignant cases
      (7.4%; 95% CI: 2.4%, 18.1%) demonstrated margins positive for cancer that
      required re-excision. Five of 110 radiographs of the specimen (4.5%; 95% CI:
      1.7%, 10.4%) demonstrated increased distance between the target and reflector
      distance of greater than 1.0 cm (range, 1.1-2.6 cm) compared with postprocedure
      mammogram the day of placement, three of five were associated with hematomas, two
      of five migrated without identifiable cause. No related postoperative
      complications were identified. Conclusion Savi Scout is an accurate, reliable
      method to localize and excise breast lesions with acceptable margin positivity
      and re-excision rates. Bracketing is possible with reflectors as close as 2.6 cm.
      Savi Scout overcomes many limitations of other localization methods, which
      warrants further study. (c) RSNA, 2017.

PMID- 28430554
TI  - Notice of retraction: Role of Cerebrospinal Fluid in Spaceflight-induced Ocular
      Changes and Visual Impairment in Astronauts.
AB  - Notice of retraction: the article "Role of Cerebral Spinal Fluid in Space Flight
      Induced Ocular Changes and Visual Impairment in Astronauts" by Alperin et al This
      article has been retracted due to security concerns raised by NASA, the
      sponsoring agency. (c) RSNA, 2017.

PMID- 28430553
TI  - Sport Concussion Management Using Facebook: A Feasibility Study of an Innovative
      Adjunct "iCon".
AB  - CONTEXT:   Sport concussion is currently the focus of much international
      attention. Innovative methods to assist athletic trainers in facilitating
      management after this injury need to be investigated. OBJECTIVE:   To investigate
      the feasibility of using a Facebook concussion-management program termed iCon
      (interactive concussion management) to facilitate the safe return to play (RTP)
      of young persons after sport concussion. DESIGN:   Observational study. SETTING: 
      Facebook group containing interactive elements, with moderation and support from
      trained health care professionals. PATIENTS OR OTHER PARTICIPANTS:   Eleven
      participants (n = 9 men, n = 2 women; range, 18 to 28 years old) completed the
      study. DATA COLLECTION AND ANALYSIS:   The study was conducted over a 3-month
      period, with participant questionnaires administered preintervention and
      postintervention. The primary focus was on the qualitative experiences of the
      participants and the effect of iCon on their RTP. Usage data were also collected.
      RESULTS:   At the completion of the study, all participants (100%) stated that
      they would recommend an intervention such as iCon to others. Their supporting
      quotes all indicated that iCon has the potential to improve the management of
      concussion among this cohort. Most participants (n = 9, 82%) stated they were
      better informed with regard to their RTP due to participating in iCon.
      CONCLUSIONS:   This interactive adjunct to traditional concussion management was
      appreciated among this participant group, which indicates the feasibility of a
      future, larger study of iCon. Athletic trainers should consider the role that
      multimedia technologies may play in assisting with the management of sport
      concussion.

PMID- 28430556
TI  - Pneumoconioses Radiographs in a Large Population of U.S. Coal Workers:
      Variability in A Reader and B Reader Classifications by Using the International
      Labour Office Classification.
AB  - Purpose To assess the level of concordance between chest radiographic
      classifications of A and B Readers in a national surveillance program offered to
      U.S. coal miners over an approximate 36-year period. Materials and Methods The
      National Institute for Occupational Safety and Health (NIOSH) Coal Workers'
      Health Surveillance Program (CWHSP) is a surveillance program with nonresearch
      designation and is exempt from Human Subjects Review Board approval (11-DRDS
      NR03). Thirty-six years of data (1979-2015) from the CWHSP were analyzed, which
      included all conventional screen-film radiographs with a classification by at
      least one A Reader and one B Reader. Agreement was assessed by using kappa
      statistics; prevalence ratios were used to describe differences between A and B
      Reader determinations of image technical quality, small opacity profusion, and
      presence of large opacities and pleural abnormalities. Results The analysis
      included 79 185 matched A and B Reader chest radiograph classifications. A
      majority of both A and B Readers were radiologists (74.2% [213 of 287] vs 64.7%
      [22 of 34]; P = .04). A and B Readers had minimal agreement on technical image
      quality (kappa = 0.0796; 95% confidence interval [CI]: 0.07, 0.08) and the
      distribution of small opacity profusion (subcategory kappa, 0.2352; 95% CI: 0.22,
      0.25). A Readers classified more images as "good" quality (prevalence ratio,
      1.38; 95% CI: 1.35, 1.41) and identified more pneumoconiosis (prevalence ratio,
      1.22; 95% CI: 1.20, 1.23). Conclusion A Readers classified substantially more
      radiographs with evidence of pneumoconiosis and classified higher small opacity
      profusion compared with B Readers. These observations reinforce the importance of
      multiple classifications by readers who have demonstrated ongoing competence in
      the International Labour Office classification system to ensure accurate
      radiographic classifications. (c) RSNA, 2017.

PMID- 28430552
TI  - The Inter-Association Task Force Document on Emergency Health and Safety: Best
      Practice Recommendations for Youth Sports Leagues.

PMID- 28430557
TI  - Utilization Management of High-Cost Imaging in an Outpatient Setting in a Large
      Stable Patient and Provider Cohort over 7 Years.
AB  - Purpose To quantify the effect of a comprehensive, long-term, provider-led
      utilization management (UM) program on high-cost imaging (computed tomography,
      magnetic resonance imaging, nuclear imaging, and positron emission tomography)
      performed on an outpatient basis. Materials and Methods This retrospective, 7
      year cohort study included all patients regularly seen by primary care physicians
      (PCPs) at an urban academic medical center. The main outcome was the number of
      outpatient high-cost imaging examinations per patient per year ordered by the
      patient's PCP or by any specialist. The authors determined the probability of a
      patient undergoing any high-cost imaging procedure during a study year and the
      number of examinations per patient per year (intensity) in patients who underwent
      high-cost imaging. Risk-adjusted hierarchical models were used to directly
      quantify the physician component of variation in probability and intensity of
      high-cost imaging use, and clinicians were provided with regular comparative
      feedback on the basis of the results. Observed trends in high-cost imaging use
      and provider variation were compared with the same measures for outpatient
      laboratory studies because laboratory use was not subject to UM during this
      period. Finally, per-member per-year high-cost imaging use data were compared
      with statewide high-cost imaging use data from a major private payer on the basis
      of the same claim set. Results The patient cohort steadily increased in size from
      88 959 in 2007 to 109 823 in 2013. Overall high-cost imaging utilization went
      from 0.43 examinations per year in 2007 to 0.34 examinations per year in 2013, a
      decrease of 21.33% (P < .0001). At the same time, similarly adjusted routine
      laboratory study utilization decreased by less than half that rate (9.4%, P <
      .0001). On the basis of unadjusted data, outpatient high-cost imaging utilization
      in this cohort decreased 28%, compared with a 20% decrease in statewide
      utilization (P = .0023). Conclusion Analysis of high-cost imaging utilization in
      a stable cohort of patients cared for by PCPs during a 7-year period showed that
      comprehensive UM can produce a significant and sustained reduction in risk
      adjusted per-patient year outpatient high-cost imaging volume. (c) RSNA, 2017.

PMID- 28430558
TI  - Lower Esophageal Sphincter Augmentation for Gastroesophageal Reflux Disease: The
      Safety of a Modern Implant.
AB  - INTRODUCTION: Use of the magnetic sphincter augmentation device (MSAD) for
      gastroesophageal reflux disease (GERD) is increasing. As this innovative
      treatment for GERD gains widespread use and adoption, an assessment of its safety
      since U.S. market introduction is presented. METHODS: Events were collected from
      the Manufacturer and User Facility Device Experience (MAUDE) database, which
      reports events submitted to the Food and Drug Administration (FDA) of suspected
      device-associated deaths, serious injuries, and malfunctions. The reporting
      period was from March 22, 2012 (FDA approval) through May 31, 2016, and included
      only events occurring in the United States. Additional information was provided
      by the manufacturer, allowing calculation of implant rates and durations.
      RESULTS: An estimated 3283 patients underwent magnetic sphincter augmentation
      (165 surgeons at 191 institutions). The median implant duration was 1.4 years,
      with 1016 patients implanted for at least 2 years. No deaths, life-threatening
      events, or device malfunctions were reported. The overall rate of device removal
      was 2.7% (89/3283). The most common reasons for device removal were dysphagia
      (52/89) and persistent reflux symptoms (19/89). Removal for erosion and migration
      was 0.15% (5/3283) and 0% (0/3283), respectively. There were no perforations. Of
      the device removals, 57.3% (51/89) occurred <1 year after implant, 30.3% (27/89)
      between 1 and 2 years, and 12.4% (11/89) >2 years after implant. The rate of
      device removal and erosion with an implant duration >2 years were 1.1% (11/1016)
      and 0.1% (1/1016), respectively. All device removals and erosions were managed
      nonemergently, with no complications or long-term consequences. CONCLUSIONS:
      During a 4-year period in more than 3000 patients, no unanticipated MSAD
      complications have emerged, and there is no data to suggest a trend of increased
      events over time. The presentation and management of device-related issues have
      been less complicated than revisions for laparoscopic fundoplication or other
      interventions for GERD. MSAD is considered safe for the widespread treatment of
      GERD.

PMID- 28430559
TI  - Heart-on-a-Chip: An Investigation of the Influence of Static and Perfusion
      Conditions on Cardiac (H9C2) Cell Proliferation, Morphology, and Alignment.
AB  - Lab-on-a-chip systems are increasingly used as tools for cultures and
      investigation of cardiac cells. In this article, we present how the geometry of
      microsystems and microenvironmental conditions (static and perfusion) influence
      the proliferation, morphology, and alignment of cardiac cells (rat
      cardiomyoblasts-H9C2). Additionally, studies of cell growth after incubation with
      verapamil hydrochloride were performed. For this purpose, poly(dimethylsiloxane)
      (PDMS)/glass microfluidic systems with three different geometries of
      microchambers (a circular chamber, a longitudinal channel, and three parallel
      microchannels separated by two rows of micropillars) were prepared. It was found
      that static conditions did not enhance the growth of H9C2 cells in the
      microsystems. On the contrary, perfusion conditions had an influence on division,
      morphology, and the arrangement of the cells. The highest number of cells, their
      parallel orientation, and their elongated morphology were obtained in the
      longitudinal microchannel. It showed that this kind of microsystem can be used to
      understand processes in heart tissue in detail and to test newly developed
      compounds applied in the treatment of cardiac diseases.

PMID- 28430560
TI  - Database-Centric Method for Automated High-Throughput Deconvolution and Analysis
      of Kinetic Antibody Screening Data.
AB  - The state-of-the-art industrial drug discovery approach is the empirical
      interrogation of a library of drug candidates against a target molecule. The
      advantage of high-throughput kinetic measurements over equilibrium assessments is
      the ability to measure each of the kinetic components of binding affinity.
      Although high-throughput capabilities have improved with advances in instrument
      hardware, three bottlenecks in data processing remain: (1) intrinsic molecular
      properties that lead to poor biophysical quality in vitro are not accounted for
      in commercially available analysis models, (2) processing data through a user
      interface is time-consuming and not amenable to parallelized data collection, and
      (3) a commercial solution that includes historical kinetic data in the analysis
      of kinetic competition data does not exist. Herein, we describe a generally
      applicable method for the automated analysis, storage, and retrieval of kinetic
      binding data. This analysis can deconvolve poor quality data on-the-fly and store
      and organize historical data in a queryable format for use in future analyses.
      Such database-centric strategies afford greater insight into the molecular
      mechanisms of kinetic competition, allowing for the rapid identification of
      allosteric effectors and the presentation of kinetic competition data in absolute
      terms of percent bound to antigen on the biosensor.

PMID- 28430561
TI  - Association of GII.P16-GII.2 Recombinant Norovirus Strain with Increased
      Norovirus Outbreaks, Guangdong, China, 2016.
AB  - An unusual prevalence of recombinant GII.2 noroviruses (GII.P16-GII.2) in
      Guangdong, China, at the end of 2016 caused a sharp increase in outbreaks of
      acute gastroenteritis. This event was another non-GII.4 epidemic that emerged
      after the GII.17 viruses in 2014 and 2015 and warrants global surveillance.

PMID- 28430562
TI  - Competence of Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus
      Mosquitoes as Zika Virus Vectors, China.
AB  - In China, the prevention and control of Zika virus disease has been a public
      health threat since the first imported case was reported in February 2016. To
      determine the vector competence of potential vector mosquito species, we
      experimentally infected Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus
      mosquitoes and determined infection rates, dissemination rates, and transmission
      rates. We found the highest vector competence for the imported Zika virus in Ae.
      aegypti mosquitoes, some susceptibility of Ae. albopictus mosquitoes, but no
      transmission ability for Cx. quinquefasciatus mosquitoes. Considering that, in
      China, Ae. albopictus mosquitoes are widely distributed but Ae. aegypti mosquito
      distribution is limited, Ae. albopictus mosquitoes are a potential primary vector
      for Zika virus and should be targeted in vector control strategies.

PMID- 28430563
TI  - Norovirus GII.P16/GII.2-Associated Gastroenteritis, China, 2016.
AB  - During October-December 2016, the number of norovirus outbreaks in China
      increased sharply from the same period during the previous 4 years. We identified
      a recombinant norovirus strain, GII.P16-GII.2, as the cause of 44 (79%) of the 56
      outbreaks, signaling that this strain could replace the predominant GII.4
      viruses.

PMID- 28430565
TI  - Do Physicians Have an Ethical Duty to Repair Relationships with So-Called
      "Difficult" Patients?
AB  - This essay argues that physicians hold primary ethical responsibility for
      repairing damaged patient-physician relationships. The first section establishes
      that the patient-physician relationship has an important influence on patient
      health and argues that physicians' duty to treat should be understood as
      including a responsibility to repair broken relationships, regardless of which
      party was "responsible" for the initial tension. The second section argues that
      the person with more power to repair the relationship also has more
      responsibility to do so and considers the moral psychology of pain as
      foundational to conceiving the patient in this case as especially vulnerable and
      disempowered. The essay concludes with suggestions for clinicians to act on the
      idea that a healthy patient-physician relationship ought to lie at the center of
      medicine's moral mission.

PMID- 28430564
TI  - Effects of Zika Virus Strain and Aedes Mosquito Species on Vector Competence.
AB  - In the Western Hemisphere, Zika virus is thought to be transmitted primarily by
      Aedes aegypti mosquitoes. To determine the extent to which Ae. albopictus
      mosquitoes from the United States are capable of transmitting Zika virus and the
      influence of virus dose, virus strain, and mosquito species on vector competence,
      we evaluated multiple doses of representative Zika virus strains in Ae. aegypti
      and Ae. albopictus mosquitoes. Virus preparation (fresh vs. frozen) significantly
      affected virus infectivity in mosquitoes. We calculated 50% infectious doses to
      be 6.1-7.5 log 10 PFU/mL; minimum infective dose was 4.2 log 10 PFU/mL. Ae.
      albopictus mosquitoes were more susceptible to infection than Ae. aegypti
      mosquitoes, but transmission efficiency was higher for Ae. aegypti mosquitoes,
      indicating a transmission barrier in Ae. albopictus mosquitoes. Results suggest
      that, although Zika virus transmission is relatively inefficient overall and
      dependent on virus strain and mosquito species, Ae. albopictus mosquitoes could
      become major vectors in the Americas.

PMID- 28430566
TI  - How Should Physicians Respond When Patients Distrust Them Because of Their
      Gender?
AB  - There are many reasons why gender-concordant care benefits patients and is
      requested by them. For training hospitals, however, such requests present
      challenges as well as opportunities in providing patient-centered care.
      Responding to a case in which a female patient who is having a routine exam
      refuses care from a male medical student, we discuss ethical principles involved
      in gender-concordant care requests, when it is appropriate to question such
      requests, and a team-based approach to responding to them.

PMID- 28430567
TI  - How Should Clinicians Respond to Medical Requests from Clinician Family Members
      of Patients?
AB  - In the medical profession, receiving a request for medical management from a
      colleague is a routine experience. However, when the colleague is a family member
      of a patient and the desired or requested medical intervention is not medically
      indicated in the attending physician's view, the situation becomes more
      complicated. Ethical issues include respect for patient autonomy and social
      justice as well as nonmaleficence. Furthermore, interpersonal and professional
      relationships may be tested in this situation. Addressing the colleague's
      concerns with empathy and respect, without compromising one's own medical
      judgment, is critical in resolving these kinds of conflicts.

PMID- 28430568
TI  - Reflection-Based Learning for Professional Ethical Formation.
AB  - One way practitioners learn ethics is by reflecting on experience. They may
      reflect in the moment (reflection-in-action) or afterwards (reflection-on
      action). We illustrate how a teaching clinician may transform relationships with
      patients and teach person-centered care through reflective learning. We discuss
      reflective learning pedagogies and present two case examples of our preferred
      method, guided group reflection using narratives. This method fosters moral
      development alongside professional identity formation in students and advanced
      learners. Our method for reflective learning addresses and enables processing of
      the most pressing ethical issues that learners encounter in practice.

PMID- 28430569
TI  - Courage and Compassion: Virtues in Caring for So-Called "Difficult" Patients.
AB  - What, if anything, can medical ethics offer to assist in the care of the
      "difficult" patient? We begin with a discussion of virtue theory and its
      application to medical ethics. We conceptualize the "difficult" patient as an
      example of a "moral stress test" that especially challenges the physician's
      character, requiring the good physician to display the virtues of courage and
      compassion. We then consider two clinical vignettes to flesh out how these
      virtues might come into play in the care of "difficult" patients, and we conclude
      with a brief proposal for how medical educators might cultivate these essential
      character traits in physicians-in-training.

PMID- 28430570
TI  - Repairing "Difficult" Patient-Clinician Relationships.
AB  - Using a case example, we offer guidance for improving "difficult" clinician
      patient relationships. These relationships may be repaired by acknowledging a
      clinician's part in conflict, empathizing with patients, identifying a patient's
      skill deficits, and employing communication and engagement techniques used by
      mental health professionals. Clinicians will inevitably take on more of the work
      of repairing damaged relationships, but doing so improves the odds of these
      patients receiving the help they need.

PMID- 28430571
TI  - Forty Years since "Taking Care of the Hateful Patient".
AB  - Using the word "hateful" is not the only option in describing patients who induce
      in clinicians feelings of dread. We suggest an alternative approach to the
      language of hate, one that seeks dignity and perhaps even a divine spark in every
      patient.

PMID- 28430572
TI  - Lessons about So-Called "Difficult" Patients from the UK Controversy over Patient
      Access to Electronic Health Records.
AB  - Increasing numbers of patients have direct access to their electronic health
      records (EHRs). Proponents of direct access argue that it empowers patients by
      making them more informed and offering them more control over their health and
      care. According to some proponents of patients' access to EHRs, clinicians'
      concerns about potential negative implications are grounded in a form of
      paternalism that protects clinicians' authority. This paper draws upon narratives
      from patients in the United Kingdom (UK) who have access to their EHRs and
      suggests strategies for moving beyond these controversies between proponents and
      critics of the system. It additionally shows that the very organizational,
      procedural, and technological infrastructure that promises patients' increased
      access to records can also exacerbate some patients' "difficult" behaviors.

PMID- 28430573
TI  - Roles of Physicians and Health Care Systems in "Difficult" Clinical Encounters.
AB  - Physicians are, by definition, contributing partners in "difficult" patient
      physician encounters. Although research on relevant physician qualities is
      limited, common themes mirror the more extensive literature on physician burnout.
      Focusing on primary care, we discuss physician-level factors in difficult
      encounters related to psychosocial attitudes and self-awareness, communication
      skills, and practice environments. Potential approaches to mitigating these
      factors include changes to medical training, such as structured peer case
      discussion groups and communication skills development, and changes to workplace
      environments, such as integrated mental health. Modifying physician-level factors
      in difficult encounters could ease perceived difficulties and improve outcomes
      for both physicians and patients.

PMID- 28430574
TI  - How Navigating Uncertainty Motivates Trust in Medicine.
AB  - Three significant factors in the shaping of modern medicine contribute to broad
      perceptions about trust in the patient-physician relationship: moral,
      professional, and epidemiological uncertainty. Trusting a physician depends first
      on trusting a person, then trusting a person's skills and training, and finally
      trusting the science that underwrites those skills. This essay, in part based on
      my book, Trusting Doctors: The Decline of Moral Authority in American Medicine
      (Princeton University Press, 2008), will address the forms of uncertainty that
      contribute to the nature of difficult encounters in the patient-physician
      relationship.

PMID- 28430575
TI  - Nested Tensions in Care.
AB  - This project presents research-based art works that inquire into the tensions in
      everyday life from an ethical viewpoint of care, which sees people as embedded,
      "nested" in care-based relationships. Trust is the glue that holds these "nests"
      together. Care is the air that lifts them up, but tensions exist as well-between
      dependency and autonomy, vulnerability and strength, for example. The pull of
      these ideas exist in a kind of "check" and run through our relations and being.

PMID- 28430576
TI  - Ezrin activation by LOK phosphorylation involves a PIP2-dependent wedge
      mechanism.
AB  - How cells specify morphologically distinct plasma membrane domains is poorly
      understood. Prior work has shown that restriction of microvilli to the apical
      aspect of epithelial cells requires the localized activation of the membrane-F
      actin linking protein ezrin. Using an in vitro system, we now define a multi-step
      process whereby the kinase LOK specifically phosphorylates ezrin to activate it.
      Binding of PIP2 to ezrin induces a conformational change permitting the insertion
      of the LOK C-terminal domain to wedge apart the membrane and F-actin-binding
      domains of ezrin. The N-terminal LOK kinase domain can then access a site 40
      residues distal from the consensus sequence that collectively direct
      phosphorylation of the appropriate threonine residue. We suggest that this
      elaborate mechanism ensures that ezrin is only phosphorylated at the plasma
      membrane, and with high specificity by the apically localized kinase LOK.

PMID- 28430577
TI  - Synthetic lethal interaction between the tumour suppressor STAG2 and its paralog
      STAG1.
AB  - Cohesin is a multi-protein complex that tethers sister chromatids during mitosis
      and mediates DNA repair, genome compartmentalisation and regulation of gene
      expression. Cohesin subunits frequently acquire cancer loss-of-function
      alterations and act as tumour suppressors in several tumour types. This has led
      to increased interest in cohesin as potential target in anti-cancer therapy. Here
      we show that the loss-of-function of STAG2, a core component of cohesin and an
      emerging tumour suppressor, leads to synthetic dependency of mutated cancer cells
      on its paralog STAG1. STAG1 and STAG2 share high sequence identity, encode
      mutually exclusive cohesin subunits and retain partially overlapping functions.
      We inhibited STAG1 and STAG2 in several cancer cell lines where the two genes
      have variable mutation and copy number status. In all cases, we observed that the
      simultaneous blocking of STAG1 and STAG2 significantly reduces cell
      proliferation. We further confirmed the synthetic lethal interaction developing a
      vector-free CRISPR system to induce STAG1/STAG2 double gene knockout. We provide
      strong evidence that STAG1 is a promising therapeutic target in cancers with
      inactivating alterations of STAG2.

PMID- 28430578
TI  - Involvement of Polo-like kinase 1 (Plk1) in quiescence regulation of cancer stem
      like cells of the gastric cancer cell lines.
AB  - Cancer stem cells (CSCs) have been hypothesized to initiate tumor growth and be
      resistant to chemoradiotherapy, and these processes appear to be closely related
      to CSC quiescence. Here, a CSC-like cell population with a high level of CD44
      expression was obtained from the human gastric cancer cell lines MKN45 and MKN74.
      Using a PKH26-labeling retention assay, quiescent CSC-like cells with low levels
      of Ki67 and PCNA expression were found in spheres formed in serum-free medium,
      and exhibited resistance to drug and radiation treatments. Polo-like kinase 1
      (Plk1) and ribosomal S6 kinase 1 (RSK1) were silenced in the quiescent CSC-like
      cells. The Plk1-specific inhibitors inhibited the activation of RSK1 and induced
      quiescence in the CSC-like cells, but increased RSK1 activity and resulted in
      apoptosis in non-CSCs. Furthermore, RSK1 silencing by inhibitors activated Plk1
      and had no effect on the growth of spheres in the CSC-like cells, but did not
      affect phosphorylation of Plk1 and led to decreased proliferation in non-CSCs.
      Our results showed that Plk1 and RSK1 play important roles in the conversion of
      CSCs between active and quiescent states.

PMID- 28430579
TI  - Antiangiogenesis and gene aberration-related therapy may improve overall survival
      in patients with concurrent KRAS and TP53 hotspot mutant cancer.
AB  - PURPOSE: Genetic alterations such as activating KRAS and/or inactivating TP53 are
      thought to be the most common drivers to tumorigenesis. Therefore, we assessed
      phase I cancer patients with KRAS+/TP53+ mutations. RESULTS: Approximately 8% of
      patients referred to phase I clinical trials harbored concurrent KRAS and TP53
      mutations. Patients who received a phase I trial therapy (n = 57) had a median OS
      of 12 months, compared with 4.6 months in those who were not treated (n = 106; p
      = 0.003). KRAS G13 and TP53 R273 mutations were associated with poor overall
      survival (OS), while antiangiogenesis and gene aberration-related therapies were
      associated with prolonged OS. A prognostic model using neutrophilia,
      thrombocytosis, hypoalbuminemia, body mass index <30 kg/m2, and the absence of
      lung metastasis was established and validated. Phase I cancer patients in the low
      risk group had a median OS of 16.6 months compared with 5.4 months in the high
      risk group (p < 0.001). Untreated patients in the low-risk group had a median OS
      of 6.7 months compared with 3.6 months in the high-risk group (p = 0.033).
      EXPERIMENTAL DESIGN: We analyzed 163 consecutive patients with advanced
      KRAS+/TP53+ mutant cancer who were referred to phase I clinical trials, to
      identify molecular aberrations, clinical characteristics, survivals, and
      potentially effective treatment regimens. CONCLUSIONS: This study provided
      preliminary evidence that besides modulation of the proinflammatory state,
      antiangiogensis and concomitant gene aberration-related therapies may improve the
      treatment of KRAS+/TP53+ mutant cancer.

PMID- 28430580
TI  - Expression status of folate receptor alpha is a predictor of survival in
      pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognosis among
      malignancies. Thus, the identification of markers useful in developing innovative
      diagnostic and therapeutic methods is an imperative need. Folate receptor alpha
      (FRalpha) has been associated with prognosis in several cancers and has served as
      a target of novel anti-tumor therapies. However, FRalpha expression in PDAC and
      its correlation with the clinical course of the disease has not been thoroughly
      investigated. In this study, we analyzed FRalpha expression in 140 PDAC specimens
      and 7 PDAC cell lines in order to define the significance of FRalpha expression
      in PDAC and its potential role as a target for immunotherapy. Immunohistochemical
      analysis demonstrated that FRalpha expression intensity was low, intermediate and
      high in 22(16%), 73(52%) and 45(32%) PDACs, respectively. The staining was
      located in both membrane and cytoplasm in most cases (123, 88%). Lower FRalpha
      expression was associated with cigarette smoking (p<0.001), alcohol consumption
      (p<0.001), and lymphovascular invasion (p=0.002). Additionally, lower FRalpha
      expression was associated with poor overall survival (5-year overall survival:
      low 13%, intermediate 31%, high 33%; p=0.006). FRalpha expression (HR=0.61;
      p=0.03) and Charlson Comorbidity Index (HR=1.16; p=0.01) emerged as independent
      predictors of survival. The analysis by flow cytometry of 7 PDAC cell lines (AsPC
      1, Capan-2, MIA PaCa-2, PANC-1, PDAC2, PDAC3, and PDAC5) demonstrated the highest
      expression of FRalpha on the PDAC3 cell line (45%). Therefore, a higher FRalpha
      expression is predictive of a favorable prognosis in PDAC and FRalpha may
      represent a promising target for novel treatments, including immunotherapy.

PMID- 28430581
TI  - Association between EN1 rs4144782 and susceptibility of knee osteoarthritis: A
      case-control study.
AB  - Osteoarthritis (OA) is a complex disease that affects the whole joint, resulting
      from the combined influence of biomechanical factors and genetic factors. The
      heritable component for primary OA accounts for about 60% of variation in
      population liability to the disease. So far, genome-wide association studies
      (GWAS) and candidate gene studies have established many OA-related loci. However,
      these findings account for only a rather small fraction of the genetic component.
      To further reveal the genetic architecture of OA, we conducted this case-control
      study to explore the association of locus EN1 rs4144782 and knee OA
      susceptibility in a Chinese population. EN1 rs4144782 was significantly
      associated with increased risk of knee OA (OR=1.26; 95% CI: 1.05-1.50, P
      value=0.012). In dominant model, compared with carriers of GG genotype, those
      with AG or AA genotype have an 1.44-fold increased risk of OA (OR: 1.44; 95% CI:
      1.10-1.88; P value=0.008). Subgroup analyses didn't change the results
      materially. This should be the first association study of EN1 locus on risk of
      OA, and our finding suggested that the EN1 rs4144782 might contribute to the
      susceptibility of knee OA.

PMID- 28430582
TI  - LncRNA CHRF-induced miR-489 loss promotes metastasis of colorectal cancer via
      TWIST1/EMT signaling pathway.
AB  - microRNA-489 (miR-489) is a novel cancer-related miRNAs and functions as a tumor
      suppressor in human cancers. While, the clinical significance of miR-489 and its
      role in colorectal cancer (CRC) remain rarely known. Here, we found that the
      levels of miR-489 in CRC tissues were significantly lower than those in matched
      tumor-adjacent tissues. Furthermore, decreased levels of miR-489 also observed in
      CRC cell lines compared to HIEC cells. Clinicopathological analysis revealed that
      miR-489 underexpression was positively correlated with advanced pT stage, pN
      stage and AJCC stage. Moreover, miR-489 low expressing CRC patients showed a
      obvious shorter survival. Functionally, miR-489 restoration inhibited cell
      migration and invasion as well as epithelial-mesenchymal transition (EMT) in
      HCT116 cells, while miR-489 loss facilitated these cellular processes in SW480
      cells. In vivo experiments revealed that miR-489 overexpression reduced the
      number of metastatic nodules in nude mice liver. Notably, TWIST1 was recognized
      as a direct downstream target of miR-489 in CRC cells. Interestingly, TWIST1
      restoration abrogated the effects of miR-489 on CRC cells with enhanced cell
      migration, invasion and EMT process. Furthermore, overexpression of long
      noncoding RNA cardiac hypertrophy-related factor (lncRNA CHRF) was inversely
      correlated with miR-489 expression in CRC tissues. CHRF knockdown increased the
      expression of miR-489 and suppressed EMT events of HCT116 cells, while CHRF
      overexpression showed opposite effects on miR-489 expression and EMT in SW480
      cells. Taken together, this work support the first evidence that lncRNA CHRF
      induced miR-489 loss facilitates metastasis and EMT process of CRC cells probably
      via TWIST1/EMT signaling pathway.

PMID- 28430583
TI  - Non-invasive prediction of the tumor growth rate using advanced diffusion models
      in head and neck squamous cell carcinoma patients.
AB  - We assessed parameters of advanced diffusion weighted imaging (DWI) models for
      the prediction of the tumor growth rate in 55 head and neck squamous cell
      carcinoma (HNSCC) patients. The DWI acquisition used single-shot spin-echo echo
      planar imaging with 12 b-values (0-2000). We calculated 14 DWI parameters using
      mono-exponential, bi-exponential, tri-exponential, stretched exponential and
      diffusion kurtosis imaging models. We directly measured the tumor growth rate
      from two sets of different-date imaging data. We divided the patients into a
      discovery group (n = 40) and validation group (n = 15) based on their MR
      acquisition dates. In the discovery group, we performed univariate and
      multivariate regression analyses to establish the multiple regression equation
      for the prediction of the tumor growth rate using diffusion parameters. The
      equation obtained with the discovery group was applied to the validation group
      for the confirmation of the equation's accuracy. After the univariate and
      multivariate regression analyses in the discovery-group patients, the estimated
      tumor growth rate equation was established by using the significant parameters of
      intermediate diffusion coefficient D2 and slow diffusion coefficient D3 obtained
      by the tri-exponential model. The discovery group's correlation coefficient
      between the estimated and directly measured tumor growth rates was 0.74. In the
      validation group, the correlation coefficient (r = 0.66) and intra-class
      correlation coefficient (0.65) between the estimated and directly measured tumor
      growth rates were respectively good. In conclusion, advanced DWI model parameters
      can be a predictor for determining HNSCC patients' tumor growth rate.

PMID- 28430585
TI  - FOXD3 regulates anaplastic thyroid cancer progression.
AB  - Anaplastic thyroid cancer (ATC) is an aggressive malignancy with poor prognosis.
      It was reported that Forkhead box D3 (FOXD3) transcription factor is associated
      with several cancers. We investigated its antitumorigenic role of ATC in this
      study. The ATC cell lines SW1736 and K18 exhibited lower FOXD3 expression than
      the Nthy-ori-3-1 normal thyroid cell line. FOXD3 downregulation in ATC cell lines
      promoted invasiveness and epithelial-to-mesenchymal transition (EMT) and
      decreased cellular apoptosis. FOXD3 silencing also enhanced p-ERK levels in the
      ATC cell lines, suggesting it negatively regulated MAPK/ERK signaling. Silencing
      FOXD3 in SW1736 cells also led to generation of larger xenograft tumors with high
      p-ERK and low E-cadherin levels. Moreover, human ATC samples showed lower FOXD3
      and higher p-ERK levels than samples of normal thyroid tissue. These findings
      demonstrate that FOXD3 acts as a tumor suppressor during anaplastic thyroid
      carcinogenesis and highlight its potential for clinical application.

PMID- 28430586
TI  - Epidermal growth factor receptor (EGFR): A rising star in the era of precision
      medicine of lung cancer.
AB  - Lung cancer is a leading cause of cancer mortality worldwide. In tumors, the
      important role of noncoding RNA regulatory networks has been more and more
      reveal. EGFR has been identified as an oncogenic driver of NSCLC, especially
      activating mutations EGFR and its inhibition with specific TKIs can generate
      dramatic tumor responses. Studies have shown that EGFR plays significant roles in
      the progression of NSCLC. Subset analysis of the small proportion of patients
      with EGFR-mutant lung cancer showed a disease-free survival benefit, but was
      underpowered to detect a survival advantage. Herein, we highlight the progression
      of EGFR, noncoding RNA, and their roles in carcinogenesis. We also focus on anti
      lung cancer drug development and EGFR-related drug resistance.

PMID- 28430588
TI  - Chronic grouped social restriction triggers long-lasting immune system
      adaptations.
AB  - Chronic stress triggers rigorous psychological and physiological changes,
      including immunological system adaptations. However, the effects of long-term
      social restriction on human immune system have not been investigated. The present
      study is to investigate the effect of chronic stress on immune changes in human
      blood, with the stress stimuli controlled.10 male volunteers were group isolated
      from the modern society in a 50-meter-square room for 150 days, with enriched
      nutrition and good living conditions provided. Serum examination of immune system
      markers demonstrated numerous changes in different aspects of the immune
      functions. The changes were observed as early as 30 days and could last for
      another 150 days after the termination of the restriction period (300 days' time
      point). The results strongly argued for the adaptation of immunological system
      under chronic social restriction stress in adult human, preceding a clear change
      in psychological conditions. The changes of these immune system factors could as
      well act as the serum biomarkers in clinical early-diagnosis of stress-related
      disorders.

PMID- 28430587
TI  - Parkin regulates translesion DNA synthesis in response to UV radiation.
AB  - Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD).
      Notably, PD patients also exhibit a significantly higher risk in melanoma and
      other skin tumors, while the mechanism remains largely unknown. In this study, we
      show that depletion of Parkin causes compromised cell viability and genome
      stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes
      efficient Rad18-dependent proliferating cell nuclear antigen (PCNA)
      monoubiquitination by facilitating the formation of Replication protein A (RPA)
      coated ssDNA upon UV radiation. Furthermore, Parkin is found to physically
      interact with NBS1 (Nijmegen breakage syndrome 1), and to be required for optimal
      recruitment of NBS1 and DNA polymerase eta (Poleta) to UV-induced damage sites.
      Consequently, depletion of Parkin leads to increased UV-induced mutagenesis.
      These findings unveil an important role of Parkin in protecting genome stability
      through positively regulating translesion DNA synthesis (TLS) upon UV damage,
      providing a novel mechanistic link between Parkin deficiency and predisposition
      to skin cancers in PD patients.

PMID- 28430589
TI  - IER5 as a promising predictive marker promotes irradiation-induced apoptosis in
      cervical cancer tissues from patients undergoing chemoradiotherapy.
AB  - PURPOSE: To define the role of immediate-early 5 (IER5) gene as a promising
      biomarker in predicting the radiosensitivity and prognosis of cervical cancer
      patients receiving cisplatin-based concurrent chemoradiotherapy (DDP-CCRT).
      RESULTS: Our investigations found that IER5 level was markedly elevated in
      cervical cancer patients after being treated with irradiation, which indicated
      IER5 was closely dose induced. By contrast, the correlation between IER5 and
      radiosensitivity cannot be confirmed by the present study. The up-regulation of
      IER5 expression effectively increased cell apoptosis after administration of
      irradiation (P < 0.05). Using an ANOVA model for repeated-measures, we found
      significant association between the IER5 level and tumor size (P < 0.05).
      MATERIALS AND METHODS: Forty-three cervical cancer patients stage IIb-IIIb
      received DDP-CCRT were registered. Biopsy tissues were obtained after
      administration of irradiation dose of 0 Gy, 2~6 Gy, 10 Gy, 20 Gy, 30 Gy,
      respectively. The IER5 protein and mRNA levels were measured by
      immunohistochemistry, western blot and quantitative polymerase chain reaction,
      respectively; besides, the apoptosis rate was assessed by transferase-mediated
      dUTP nick end labeling. CONCLUSIONS: Mechanistically, we confirmed that IER5
      induced by radiation dose enhanced apoptosis of cervical cancer, was inversely
      associated with tumor size. In conclusion, our studies indicate target IER5 is
      improved to be a potential radiosensitizer for developing effective therapeutic
      strategies against cervical cancer to radiotherapy and a predictive biomarker for
      radiosensitivity.

PMID- 28430590
TI  - Treatment of esophageal cancer with radiation therapy -a pan-Chinese survey of
      radiation oncologists.
AB  - Lots of controversies were found about the treatment in relation to radiation
      therapy (RT) for esophageal squamous cell carcinoma (ESCC). We designed a
      questionnaire of these controversies to do a pan-Chinese survey of radiation
      oncologists (ROs). For operable ESCC, 53% ROs chose surgery plus postoperative
      chemoradiotherapy (CRT), while 40% chose preoperative CRT plus surgery. For
      target volume of postoperative RT, most ROs (92%) would delineate tumor bed plus
      involved lymph nodes region before surgery. For definitive RT, most ROs (81%)
      would give patients higher RT dose to 60-65Gy. For radiation target volume, most
      ROs would give patients prophylactic irradiation of the bilateral superclavicular
      lymph nodes region for cervical ESCC (93%), and the left gastric lymph nodes
      region for lower thoracic ESCC (72%). For the treatment of mediastinal lymph
      nodes, 72% ROs preferred elective nodal irradiation, while 28% did the involved
      nodal irradiation. For concurrent chemotherapy regimen, PF (5-Fu + cisplatin) and
      TP (cisplatin + paclitaxel) were used widely (49% and 46%, respectively). During
      simulation, four-dimensional computer tomography (4D CT) was not widely used
      (48%), even for cervical or lower thoracic ESCC (52%). For daily RT delivery,
      only 66% ROs would perform imaging guidance RT daily. In summary, more
      controversies existed in the treatment of ESCC with RT in China, including
      treatment strategy, radiation dose and target contour. Future goals include
      standardization of treatment strategy, radiation dose, and target contour, and
      application of 4D CT and daily imaging guidance, and pursuit of randomized trials
      in Chinese population.

PMID- 28430592
TI  - Resveratrol protects against early polymicrobial sepsis-induced acute kidney
      injury through inhibiting endoplasmic reticulum stress-activated NF-kappaB
      pathway.
AB  - Resveratrol, a polyphenol compound derived from various edible plants, protects
      against sepsis-induced acute kidney injury (AKI) via its anti-inflammatory
      activity, but the underlying mechanisms remain largely unknown. In this study, a
      rat model of sepsis was established by cecal ligation and puncture (CLP), 30
      mg/kg resveratrol was intraperitoneally administrated immediately after the CLP
      operation. HK-2 cells treated by 1 MUg/ml lipopolysaccharide, 0.2 MUM
      tunicamycin, 2.5 mM irestatin 9389 and 20 MUM resveratrol were used for in vitro
      study. The results demonstrated that resveratrol significantly improved the renal
      function and tubular epithelial cell injury and enhanced the survival rate of CLP
      induced rat model of sepsis, which was accompanied by a substantial decrease of
      the serum content and renal mRNA expressions of TNF-alpha, IL-1beta and IL-6. In
      addition, resveratrol obviously relieved the endoplasmic reticulum stress,
      inhibited the phosphorylation of inositol-requiring enzyme 1(IRE1) and nuclear
      factor-kappaB (NF-kappaB) in the kidney. In vitro studies showed that resveratrol
      enhanced the cell viability, reduced the phosphorylation of NF-kappaB and
      production of inflammatory factors in lipopolysaccharide and tunicamycin-induced
      HK-2 cells through inhibiting IRE1 activation. Taken together, administration of
      resveratrol as soon as possible after the onset of sepsis could protect against
      septic AKI mainly through inhibiting IRE1-NF-kappaB pathway-triggered
      inflammatory response in the kidney. Resveratrol might be a readily translatable
      option to improve the prognosis of sepsis.

PMID- 28430593
TI  - Genetic variants within the cancer susceptibility region 8q24 and ovarian cancer
      risk in Han Chinese women.
AB  - Accumulating evidence suggests that genetic variants at chromosome 8q24 confer
      susceptibility to various types of cancer. This case-control study was designed
      to explore the relationship between genetic variants at 8q24 and ovarian cancer
      risk in Han Chinese women. Two variants (rs13281615 A > G and rs6983267 T > G)
      were genotyped in 377 ovarian cancer cases and 1034 cancer-free controls using
      TaqMan allelic discrimination assay. Logistic regression analysis revealed that
      the G allele of rs6983267 was significantly associated with increased risk of
      ovarian cancer (additive model: adjusted OR = 1.21, 95% CI = 1.01-1.43, P =
      0.048; recessive model: adjusted OR = 1.51, 95% CI = 1.06-2.15, P = 0.023).
      However, no significant association was observed between rs13281615 and ovarian
      cancer. In stratified analysis, the risk effect of rs6983267 variant remained
      significant in premenopausal women (additive model: adjusted OR = 1.62, 95% CI =
      1.18-2.23, P = 0.003). Summarily, this study suggested that 8q24 rs6983267 may
      contribute to the susceptibility of ovarian cancer in premenopausal Han Chinese
      women, supporting the pleiotropy of 8q24 in carcinogenesis.

PMID- 28430591
TI  - Poly(adenosine diphosphate-ribose) polymerase as therapeutic target: lessons
      learned from its inhibitors.
AB  - Poly(ADP-ribose) polymerases are a family of DNA-dependent nuclear enzymes
      catalyzing the transfer of ADP-ribose moieties from cellular nicotinamide-adenine
      dinucleotide to a variety of target proteins. Although they have been considered
      as resident nuclear elements of the DNA repair machinery, recent works revealed a
      more intricate physiologic role of poly(ADP-ribose) polymerases with numerous
      extranuclear activities. Indeed, poly(ADP-ribose) polymerases participate in
      fundamental cellular processes like chromatin remodelling, transcription or
      regulation of the cell-cycle. These new insight into the physiologic roles of
      poly(ADP-ribose) polymerases widens the range of human pathologies in which
      pharmacologic inhibition of these enzymes might have a therapeutic potential.
      Here, we overview our current knowledge on extranuclear functions of poly(ADP
      ribose) polymerases with a particular focus on the mitochondrial ones and discuss
      potential fields of future clinical applications.

PMID- 28430595
TI  - Minus end-directed kinesin-14 KIFC1 regulates the positioning and architecture of
      the Golgi apparatus.
AB  - The Golgi apparatus is the central organelle along the eukaryotic secretory and
      endocytic pathway. In non-polarized mammalian cells, the Golgi complex is usually
      located proximal to the nucleus at the cell center and is closely associated with
      the microtubule organizing center. Microtubule networks are essential in the
      organization and central localization of the Golgi apparatus, but the molecular
      basis underlying these processes are poorly understood. Here we reveal that minus
      end-directed kinesin-14 KIFC1 proteins are required for the structural integrity
      and positioning of the Golgi complex in non-polarized mammalian cells.
      Remarkably, we found that the motor domain of kinesin-14 KIFC1 regulates the
      recognition and binding of the Golgi and KIFC1 also statically binds to the
      microtubules via its tail domain. These findings reveal a new stationary binding
      model that kinesin-14 KIFC1 proteins function as crosslinkers between the Golgi
      apparatus and the microtubules and contribute to the central positioning and
      structural maintenance of the Golgi apparatus.

PMID- 28430597
TI  - Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular
      carcinoma patients.
AB  - The systemic inflammation response index (SIRI) is a useful tool for predicting
      prognosis in some types of cancer. In this retrospective study, we evaluated the
      efficacy of SIRI in predicting overall survival in hepatocellular carcinoma (HCC)
      patients following local or systemic therapy. A cutoff value of 1.05 was
      identified for SIRI using ROC analysis in a training patient cohort. In the
      validation cohort, survival analysis revealed that median overall survival was
      longer in HCC patients with SIRI scores < 1.05 than in those with scores >= 1.05.
      Cox analysis of the validation cohort demonstrated that SIRI was associated with
      overall survival and was more predictive of overall survival that the AFP level
      or Child-Pugh score. However, SIRI and Barcelona Clinic Liver Cancer (BCLC) stage
      were equally effective for predicting survival. In addition, HCC patients with
      BCLC stage C had higher SIRI scores and poorer overall survival. SIRI also
      correlated with liver function parameters. Thus SIRI may be a convenient, low
      cost and reliable tumor marker for predicting prognosis in HCC patients.

PMID- 28430596
TI  - SNM1B/Apollo in the DNA damage response and telomere maintenance.
AB  - hSNM1B/Apollo is a member of the highly conserved beta-CASP subgroup within the
      MBL superfamily of proteins. It interacts with several DNA repair proteins and
      functions within the Fanconi anemia pathway in response to DNA interstrand
      crosslinks. As a shelterin accessory protein, hSNM1B/Apollo is also vital for the
      generation and maintenance of telomeric overhangs. In this review, we will
      summarize studies on hSNM1B/Apollo's function, including its contribution to DNA
      damage signaling, replication fork maintenance, control of topological stress and
      telomere protection. Furthermore, we will highlight recent studies illustrating
      hSNM1B/Apollo's putative role in human disease.

PMID- 28430598
TI  - Prognostic significance of SATB1 in gastrointestinal cancer: a meta-analysis and
      literature review.
AB  - BACKGROUND: The special AT-rich sequence-binding proteins 1 (SATB1) is a major
      regulator involved in cell differentiation. It has been shown that SATB1 acts as
      an oncogenic regulator. The clinical and prognostic significance of SATB1 in
      gastrointestinal cancer remains controversial. The purpose of this study is to
      conduct a systematic review and meta-analysis to elucidate the impact of SATB1 in
      gastrointestinal cancer. RESULTS: A total of 3174 gastrointestinal cancer
      patients from 15 studies were included. The correlation between SATB1 expression
      and OS or RFS was investigated in 12 and 5 studies respectively. The results of
      meta-analysis showed that SATB1 overexpression is inversely correlated with OS
      (combined HR: 1.79, p = 0.0003) and RFS (combined HR: 2.46, p < 0.0001). In
      subgroup analysis, SATB1 expression is significantly correlated with poor
      prognosis in gastrointestinal cancer in Asian population. SATB1 expression is
      associated with stage, invasion depth, lymph node metastasis and distant
      metastasis. METHODOLOGY: Published studies with data on overall survival (OS)
      and/or relapse free survival (RFS) and SATB1 expression were searched from
      Cochrane Library, PubMed and Embase (up to Dec 30, 2016). The outcome measurement
      is hazard ratio (HR) for OS or RFS related with SATB1 expression. Two reviewers
      independently screened the literatures, extracted the data and performed meta
      analysis using RevMan 5.3.0 software. The combined HRs were calculated by fixed-
      or random-effect models. CONCLUSIONS: The results of this meta-analysis suggest
      that SATB1 overexpression is related to advanced stage, lymph node metastasis and
      distant metastasis. SATB1 overexpression is a marker indicating poor prognosis in
      gastrointestinal cancer.

PMID- 28430599
TI  - TAK1 inhibitor 5Z-7-oxozeaenol sensitizes cervical cancer to doxorubicin-induced
      apoptosis.
AB  - Aberrant activation of nuclear factor-kappaB (NF-kappaB) allows cancer cells to
      escape chemotherapy-induced cell death and acts as one of the major mechanisms of
      acquired chemoresistance in cervical cancer. TAK1, a crucial mediator that
      upregulates NF-kappaB activation in response to cellular genotoxic stress, is
      required for tumor cell viability and survival. Herein, we examined whether TAK1
      inhibition is a potential therapeutic strategy for treating cervical cancer. We
      found that TAK1 inhibitor 5Z-7-oxozeaenol significantly augmented the cytotoxic
      effects of Dox in a panel of cervical cancer cell lines. Treatment with 5Z-7
      oxozeaenol hindered Dox-induced NF-kappaB activation and promoted Dox-induced
      apoptosis in cervical cancer cells. Moreover, 5Z-7-oxozeaenol showed similar
      effects in both positive and negative human papillomavirus-infected cervical
      cancer cells. Taken together, our results provide evidence that TAK1 inhibition
      significantly sensitizes cervical cancer cells to chemotherapy-induced cell death
      and supports the use of TAK1 inhibitor with current chemotherapies in the clinic
      for patients with refractory cervical cancer.

PMID- 28430600
TI  - Risk factors for the recurrence of an intracranial saccular aneurysm following
      endovascular treatment.
AB  - BACKGROUND: This study was aimed to determine risk factors for the recurrence of
      an intracranial saccular aneurysm (ISA) following endovascular treatment. The
      findings will help medical professionals to identify patients having a high risk
      of ISA recurrence and assist them in developing appropriate follow-up plans.
      RESULTS: During the follow-up period, 12.6% of the patients (83/658) experienced
      recurrent ISAs. An analysis of related factors, including gender, age,
      hypertension, diabetes mellitus, smoking, tumor size, width of the aneurysm neck,
      the presence or absence of a rupture, the volume embolization ratio (VER), the
      application or nonapplication of a stent, and follow-up time, revealed that a
      tumor size > 10 mm in diameter, wide-necked aneurysms, an anterior communicating
      or middle cerebral artery aneurysm, an aneurysm rupture, a VER < 20%, the absence
      of stent assistance, and follow-up time were high-risk factors for the recurrence
      of ISAs. MATERIALS AND METHODS: We retrospectively reviewed the records of 658
      patients who underwent endovascular treatment for ISAs from January 2010 through
      December 2014. Multivariable logistic regression was performed on the candidates'
      risk factors, which were identified via univariable screening analysis.
      CONCLUSIONS: Smoking, a large tumor size, a wide-necked aneurysm, an anterior
      communicating or middle cerebral artery aneurysm, an aneurysm rupture, a VER <
      20%, and an absence of stent assistance are significant risk factors for the
      postoperative recurrence of an aneurysm. Strict follow-up plans should be created
      for ISA patients having these high-risk factors.

PMID- 28430601
TI  - Growth-suppressive activity of raloxifene on liver cancer cells by targeting IL
      6/GP130 signaling.
AB  - BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved
      in the regulation of differentiation and growth of certain types of tumor cells.
      Constitutive activation of Signal Transducer and Activator of Transcription 3
      (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as
      a viable molecular target for liver cancer treatment. However, few inhibitors
      targeting up-streams of STAT3 are available for the therapy of liver cancer. We
      reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL
      6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous
      docking (MLSD) and drug repositioning. The possible effect of Raloxifene in STAT3
      signaling or liver cancer cells is still unclear. RESULTS: Raloxifene inhibited
      the P-STAT3 stimulated by IL-6, but not the induction of STAT1 and STAT6
      phosphorylation by IFN-gamma, IFN-alpha, and IL-4. Raloxifene inhibited STAT3
      phosphorylation and resulted in the induction apoptosis on human liver cancer
      cell-lines. Raloxifene inhibited the targets of STAT3, such as Bcl-2, Bcl-xl and
      survivin and cell viability, cell migration, and colony formation in liver cancer
      cells. Further, daily administration of Raloxifene suppressed the Hep-G2 tumor
      growth in mice in vivo. MATERIALS AND METHODS: The inhibitory effect on STAT3
      phosphorylation and activity as well as cell viability, migration, and colony
      forming ability by Raloxifene was examined in human liver cancer cells. Tumor
      growth was detected via mouse xenograft tumor mode. CONCLUSIONS: Our results
      suggest that Raloxifene is a potent IL-6/GP130 inhibitor and may be a
      chemoprevention agent for liver cancer by targeting persistent STAT3 signaling.

PMID- 28430604
TI  - Signal-transducing adaptor protein-2 promotes generation of functional long-term
      memory CD8+ T cells by preventing terminal effector differentiation.
AB  - Long-surviving memory CD8+ T cells generated by stimulation with appropriate
      tumor-associated antigens are the most aggressive and persistent tumoricidal
      effectors. In this event of memory CD8+ T cell development, the signal transducer
      and activator of transcription (STAT) proteins function as the crucial
      intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+
      T cells is not fully understood. In this study, we report for the first time, by
      using murine vaccination models, that signal-transducing adaptor protein-2
      (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by
      controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade. Following
      T cell activation, STAP2 expression was transiently reduced but was subsequently
      recovered and augmented. Analysis using small-interfering RNA (siRNA)
      demonstrated that restored STAP2 expression was associated with the activation of
      STAT3/SOCS3 signals and maintenance of cytotoxic T lymphocytes (CTLs) secondary
      responses by preventing their differentiation into terminal effector cells.
      Notably, this STAP2-dependent memory differentiation was observed in the spleen,
      but not in the lymph nodes (LNs). These findings indicate an essential role for
      STAP2 in the generation of a high-quality memory CD8+ CTLs periphery, and suggest
      the therapeutic potential of STAP2 in cancer patients.

PMID- 28430602
TI  - Fluoxetine attenuates the impairment of spatial learning ability and prevents
      neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease
      mice.
AB  - Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase
      cognitive performance in some clinical studies of Alzheimer's disease (AD).
      However, there is a lack of evidence supporting the efficacy of SSRIs as
      cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains
      largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well
      known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the
      hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1)
      transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX
      (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial
      learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water
      maze. More importantly, the number of neurons in the hippocampal DG was
      significantly increased by FLX. Additionally, FLX reduced the deposition of beta
      amyloid, inhibited GSK-3beta activity and increased the level of beta-catenin in
      middle-aged APP/PS1 mice. Collectively, the results of this study indicate that
      FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged
      AD mice, and this effect may underlie the FLX-induced improvement in learning
      ability. FLX may therefore serve as a promising therapeutic drug for AD.

PMID- 28430606
TI  - Ketamine administered pregnant rats impair learning and memory in offspring via
      the CREB pathway.
AB  - Ketamine has been reported to impair the capacity for learning and memory. This
      study examined whether these capacities were also altered in the offspring and
      investigated the role of the CREB signaling pathway in pregnant rats, subjected
      to ketamine-induced anesthesia. On the 14th day of gestation (P14), female rats
      were anesthetized for 3 h via intravenous ketamine injection (200 mg/Kg). Morris
      water maze task, contextual and cued fear conditioning, and olfactory tasks were
      executed between the 25th to 30th day after birth (B25-30) on rat pups, and rats
      were sacrificed on B30. Nerve density and dendritic spine density were examined
      via Nissl's and Golgi staining. Simultaneously, the contents of Ca2+/Calmodulin
      Dependent Protein Kinase II (CaMKII), p-CaMKII, CaMKIV, p-CaMKIV, Extracellular
      Regulated Protein Kinases (ERK), p-ERK, Protein Kinase A (PKA), p-PKA, cAMP
      Response Element Binding Protein (CREB), p-CREB, and Brain Derived Neurotrophic
      Factor (BDNF) were detected in the hippocampus. We pretreated PC12 cells with
      both PKA inhibitor (H89) and ERK inhibitor (SCH772984), thus detecting levels of
      ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. The results revealed that ketamine
      impaired the learning ability and spatial as well as conditioned memory in the
      offspring, and significantly decreased the protein levels of ERK, p-ERK, PKA, p
      PKA, p-CREB, and BDNF. We found that ERK and PKA (but not CaMKII or CaMKIV) have
      the ability to regulate the CREB-BDNF pathway during ketamine-induced anesthesia
      in pregnant rats. Furthermore, ERK and PKA are mutually compensatory for the
      regulation of the CREB-BDNF pathway.

PMID- 28430607
TI  - Simulated weightlessness affects the expression and activity of neuronal nitric
      oxide synthase in the rat brain.
AB  - Spaceflight induces pathophysiological alterations in various organs. To study
      pathophysiological adaptations to weightlessness on the ground, the tail
      suspension (TS) rat model has been used to simulate the effects of
      weightlessness. There is currently little information on the effect of TS on the
      expression and activity of nitric oxide synthase (NOS) in the brain. In this
      study, we examined time-dependent alterations in the expression and activity of
      neuronal NOS (nNOS) in the brains of TS rats. Male Sprague-Dawley rats were tail
      suspended for 1 (TS1), 7 (TS7), and 14 (TS14) days or rested on the ground for 3
      days after 14 days of TS. TS1 and TS7 rats exhibited no significant alterations
      in the expression of nNOS compared to control rats, whereas nNOS expression in
      TS14 rats was significantly upregulated compared to control rats. Normalized
      expression of nNOS mRNA and protein in TS14 rats (1.86 +/- 0.48 and 1.84 +/-
      0.29, respectively) were significantly higher than that of control rats (P <
      0.001 and P < 0.001, respectively). Consistent with these results, significant
      elevations in NOS activity and NO production were observed in TS14 rats. Thus, we
      demonstrated a significant upregulation of nNOS expression, accompanied by
      significant increases in NOS activity and NO production, in the brain of rats
      exposed to simulated weightlessness.

PMID- 28430608
TI  - Adrenalectomy abolishes hypergravity-induced gastric acid hyposecretion.
AB  - Jet fighter pilots experience high gravitational acceleration forces in the
      cephalocaudal direction (+Gz), causing severe stress. Stress affects different
      physiological functions of the gastrointestinal tract. Although the effects of
      exposure to hypergravity on cardiovascular and cerebral functions have been the
      subject of numerous studies, crucial information regarding potential
      pathophysiological alterations following hypergravity exposure in the
      gastrointestinal tract is lacking. We recently documented a significant decrease
      in gastric secretory activity in rats after acute exposure to hypergravity. In
      the present study, we investigated the effects of adrenalectomy on gastric acid
      secretion and plasma gastrin level in hypergravity-exposed rats. Male Sprague
      Dawley rats were adrenalectomized and exposed to +10Gz three times for 3 min.
      Gastric juice and blood samples were collected, and the volume and total acidity
      of gastric juice and plasma level of gastrin were measured. Consistent with our
      previous data, acute exposure to +10Gz significantly altered the gastric juice
      parameters in the sham-operated rats. The volume (P < 0.001) and acidity (P <
      0.001) of gastric juice in the hypergravity-exposed rats were significantly lower
      than those in the nonexposed rats. In contrast, in adrenalectomized rats, the
      differences in the gastric juice volume (P = 0.712) and acidity (P = 0.279) were
      not statistically significant between the hypergravity-exposed and nonexposed
      rats. We demonstrated that adrenalectomy abolished hypergravity-induced gastric
      acid hyposecretion, but did not influence gastrin release. These findings suggest
      that the adrenal glands are required for hypergravity-induced gastric acid
      hyposecretion.

PMID- 28430609
TI  - Characterization of pressure-mediated vascular tone in resistance arteries from
      bile duct-ligated rats.
AB  - In cirrhosis, changes in pressure-mediated vascular tone, a key determinant of
      systemic vascular resistance (SVR), are unknown. To address this gap in
      knowledge, we assessed ex vivo dynamics of pressurized mesenteric resistance
      arteries (diameter ~ 260 MUm) from bile duct-ligated (BDL) and sham-operated
      (SHAM) rats and determined the underlying mechanisms. At isobaric intraluminal
      pressure (70 mmHg) as well as with step-wise increase in pressure (10-110 mmHg),
      arteries from SHAM-rats constricted more than BDL-rats, and had reduced luminal
      area. In both groups, incubation with LNAME (a NOS inhibitor) had no effect on
      pressure-mediated tone, and expression of NOS isoforms were similar. TEA, which
      enhances Ca2+ influx, augmented arterial tone only in SHAM-rats, with minimal
      effect in those from BDL-rats that was associated with reduced expression of Ca2+
      channel TRPC6. In permeabilized arteries, high-dose Ca2+ and gammaGTP enhanced
      the vascular tone, which remained lower in BDL-rats that was associated with
      reduced ROCK2 and pMLC expression. Further, compared to SHAM-rats, in BDL-rats,
      arteries had reduced collagen expression which was associated with increased
      expression and activity of MMP-9. BDL-rats also had increased plasma reactive
      oxygen species (ROS). In vascular smooth muscle cells in vitro, peroxynitrite
      enhanced MMP-9 activity and reduced ROCK2 expression. These data provide evidence
      that in cirrhosis, pressure-mediated tone is reduced in resistance arteries, and
      suggest that circulating ROS play a role in reducing Ca2+ sensitivity and
      enhancing elasticity to induce arterial adaptations. These findings provide
      insights into mechanisms underlying attenuated SVR in cirrhosis.

PMID- 28430611
TI  - Prognostic value of EGFR and KRAS in circulating tumor DNA in patients with
      advanced non-small cell lung cancer: a systematic review and meta-analysis.
AB  - EGFR (exon 19 and exon 21) mutations in patients with advanced non-small cell
      lung cancer (NSCLC) treated by EGFR-TKIs are associated with a better survival;
      while KRAS mutations predict a worse prognosis. However, there are divergent
      findings regarding the prognostic value of EGFR and KRAS mutations in circulating
      tumor DNA (ctDNA). We aimed to summarize the evidence for the use of circulating
      EGFR and KRAS mutations as prognostic factors in advanced NSCLC patients.We
      searched the network databases for studies reporting progression-free survival
      (PFS) and overall survival (OS) stratified by EGFR or KRAS mutations in ctDNA in
      advanced NSCLC patients. Thirteen studies enrolling 2,293 patients were reviewed.
      Correlation of circulating EGFR or KRAS mutations with patients' prognosis was
      assessed by meta-analysis.The pooled analyses showed that EGFR mutations in ctDNA
      significantly prolong PFS (HR=0.64,95% CI 0.51-0.81, I2=0%, p=0.0002), namely, in
      patients treated by EGFR-TKIs. There is a trend to have a prolonged OS for
      advanced NSCLC patients with circulating EGFR mutations who were treated by EGFR
      TKIs (HR=0.79, 95% CI 0.52-1.21, I2=0, p=0.28). KRAS mutations detected in ctDNA
      predict a worse PFS (HR=1.83, 95% CI 1.40-2.40, p<0.0001) and OS (HR=2.07, 95% CI
      1.54-2.78, p<0.00001) in advanced NSCLC patients treated by chemotherapy.
      Sensitivity analyses and subgroup analyses demonstrated the stability of our
      conclusion.Our analysis showed that EGFR mutations in ctDNA predicted a better
      PFS, in particular in advanced NSCLC patients treated by EGFR-TKIs. KRAS
      mutations in ctDNA indicated a worse PFS and OS in patients treated by
      chemotherapy.

PMID- 28430610
TI  - Treatment of hepatocellular carcinoma with portal vein tumor thrombus: advances
      and challenges.
AB  - Portal vein tumor thrombus is a frequent, challenging complication in
      hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein
      tumor thrombus may show worse liver function, less treatment tolerance and worse
      prognosis than patients without portal vein tumor thrombus, and they may be at
      higher risk of comorbidity related to portal hypertension. Western and some Asian
      guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus
      together with metastatic hepatocellular carcinoma and therefore recommend only
      palliative treatment with sorafenib or other systemic agents. In recent years,
      more treatment options have become available for hepatocellular carcinoma
      patients with portal vein tumor thrombus, and an evidence-based approach to
      optimizing disease management and treatment has become more widespread.
      Nevertheless, consensus policies for managing hepatocellular carcinoma with
      portal vein tumor thrombus have not been established. This comprehensive
      literature review, drawing primarily on studies published after 2010, examines
      currently available management options for patients with hepatocellular carcinoma
      and portal vein tumor thrombus.

PMID- 28430612
TI  - Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to
      protect against endotoxin-induced acute hepatic failure in mice.
AB  - To investigate the effects and mechanism of diosmetin on acute hepatic failure
      (AHF), an AHF murine model was established through administration of
      lipopolysaccharides/D-galactosamine (LPS/D-GalN). In vitro, diosmetin scavenged
      free radicals. In vivo, diosmetin decreased mortality among mice, blocked the
      development of histopathological changes and hepatic damage, and suppressed
      levels of inflammatory mediators and cytokines. In addition, diosmetin prevented
      the expression of phosphorylated IKK, IkappaBalpha, and NF-kappaB p65 in the NF
      kappaB signaling pathway, and JNK and p38 in the MAPK signaling pathway.
      Diosmetin also inhibited hepatocyte apoptosis. Thus, diosmetin exerts protective
      effects against endotoxin-induced acute hepatic failure in mice. The underlying
      mechanisms are antioxidation, NF-kappaB signaling inhibition, inflammatory
      mediator/cytokine attenuation, and hepatocyte apoptosis suppression. Diosmetin is
      thus a potential drug candidate for use in the treatment of acute hepatic
      failure.

PMID- 28430613
TI  - Development of comprehensive nomograms for evaluating overall and cancer-specific
      survival of laryngeal squamous cell carcinoma patients treated with neck
      dissection.
AB  - BACKGROUND: Neck dissection for laryngeal squamous cell carcinoma (LSCC) patients
      could provide complementary prognostic information for AJCC N staging, like lymph
      node ratio (LNR). The aim of this study was to develop effective nomograms to
      better predict survival for LSCC patients treated with neck dissection. RESULTS:
      2752 patients were identified and randomly divided into training (n = 2477) and
      validation (n = 275) cohorts. The 3- and 5-year probabilities of cancer-specific
      mortality (CSM) were 30.1% and 37.2% while 3- and 5-year death resulting from
      other causes (DROC) rate were 6.2% and 11.3%, respectively. 13 significant
      prognostic factors including LNR for overall (OS) and 12 (except race) for CSS
      were enrolled in the nomograms. Concordance index as a commonly used indicator of
      predictive performance, showed the nomograms had superiority over the no-LNR
      models and TNM classification (Training-cohort: OS: 0.713 vs 0.703 vs 0.667, CSS:
      0.725 vs 0.713 vs 0.688; Validation-cohort: OS: 0.704 vs 0.690 vs 0.658, cancer
      specific survival (CSS): 0.709 vs 0.693 vs 0.672). All calibration plots revealed
      good agreement between nomogram prediction and actual survival. MATERIALS AND
      METHODS: We identified LSCC patients undergoing neck dissection diagnosed between
      1988 and 2008 from Surveillance, Epidemiology, and End Results (SEER) database.
      Optimal cutoff points were determined by X-tile program. Cumulative incidence
      function was used to analyze cancer-specific mortality (CSM) and death resulting
      from other causes (DROC). Significant predictive factors were used to establish
      nomograms estimating overall (OS) and cancer-specific survival (CSS). The
      nomograms were bootstrapped validated both internally and externally.
      CONCLUSIONS: Comprehensive nomograms were constructed to predict OS and CSS for
      LSCC patients treated with neck dissection more accurately.

PMID- 28430615
TI  - A novel mechanism of angiotensin II-regulated placental vascular tone in the
      development of hypertension in preeclampsia.
AB  - The present study tested the hypothesis that angiotensin II plays a role in the
      regulation of placental vascular tone, which contributes to hypertension in
      preeclampsia. Functional and molecular assays were performed in large and micro
      placental and non-placental vessels from humans and animals. In human placental
      vessels, angiotensin II induced vasoconstrictions in 78.7% vessels in 155 tests,
      as referenced to KCl-induced contractions. In contrast, phenylephrine only
      produced contractions in 3.0% of 133 tests. In non-placental vessels,
      phenylephrine induced contractions in 76.0% of 67 tests, whereas angiotensin II
      failed to produce contractions in 75 tests. Similar results were obtained in
      animal placental and non-placental vessels. Compared with non-placental vessels,
      angiotensin II receptors and beta-adrenoceptors were significantly increased in
      placental vessels. Compared to the vessels from normal pregnancy, angiotensin II
      induced vasoconstrictions were significantly reduced in preeclamptic placentas,
      which was associated with a decrease in angiotensin II receptors. In addition,
      angiotensin II and angiotensin converting enzyme in the maternal-placenta
      circulation in preeclampsia were increased, whereas angiotensin I and
      angiotensin1-7 concentrations were unchanged. The study demonstrates a selective
      effect of angiotensin II in maintaining placental vessel tension, which may play
      an important role in development of hypertension in preeclampsia.

PMID- 28430617
TI  - Estrogen receptors involvement in intervertebral discogenic pain of the elderly
      women: colocalization and correlation with the expression of Substance P in
      nucleus pulposus.
AB  - Estrogenic modulation of pain is an exceedingly complex phenomenon. However,
      whether estrogen is involved in discogenic low back pain still remains unclear.
      Here, immunoreactivity staining technique was used to examine the expression
      level of the estrogen receptors (ERalpha and ERbeta) and a pain related
      neuropeptide, Substance P in the lumbar intervertebral discs to analyze the
      relationship between the ERs and Substance P. Nucleus pulposus tissues of 23
      elderly female patients were harvested during spinal surgeries and made to detect
      the immunoreactivity staining of ERalpha, ERbeta and Substance P. The
      colocalization and intensities of ERs and Substance P were explored and evaluated
      respectively. The correlations between changes of ERalpha, ERbeta and Substance P
      were also assessed.Our results revealed that Substance P colocalized with ERalpha
      and ERbeta both in cytoplasm and nucleus of the nucleus pulposus cells. HSCORE
      analysis indicated that Substance P negatively correlated with both ERalpha and
      ERbeta expression. Collectively, the crosstalk between ERs and Substance P might
      exist in the disc tissue. Estrogen-dependent pain mechanism might partly be
      mediated through ERs and Substance P in the nucleus pulposus of the elderly
      females. Estrogen and its receptors might be drug targets in discogenic low back
      pain diseases.

PMID- 28430618
TI  - T-2 mycotoxin: toxicological effects and decontamination strategies.
AB  - Mycotoxins are highly diverse secondary metabolites produced in nature by a wide
      variety of fungus which causes food contamination, resulting in mycotoxicosis in
      animals and humans. In particular, trichothecenes mycotoxin produced by genus
      fusarium is agriculturally more important worldwide due to the potential health
      hazards they pose. It is mainly metabolized and eliminated after ingestion,
      yielding more than 20 metabolites with the hydroxy trichothecenes-2 toxin being
      the major metabolite. Trichothecene is hazardously intoxicating due to their
      additional potential to be topically absorbed, and their metabolites affect the
      gastrointestinal tract, skin, kidney, liver, and immune and hematopoietic
      progenitor cellular systems. Sensitivity to this type of toxin varying from dairy
      cattle to pigs, with the most sensitive endpoints being neural, reproductive,
      immunological and hematological effects. The mechanism of action mainly consists
      of the inhibition of protein synthesis and oxidative damage to cells followed by
      the disruption of nucleic acid synthesis and ensuing apoptosis. In this review,
      the possible hazards, historical significance, toxicokinetics, and the genotoxic
      and cytotoxic effects along with regulatory guidelines and recommendations
      pertaining to the trichothecene mycotoxin are discussed. Furthermore, various
      techniques utilized for toxin determination, pathophysiology, prophylaxis and
      treatment using herbal antioxidant compounds and regulatory guidelines and
      recommendations are reviewed. The prospects of the trichothecene as potential
      hazardous agents, decontamination strategies and future perspectives along with
      plausible therapeutic uses are comprehensively described.

PMID- 28430620
TI  - Genetic association between PSA-158G/A polymorphism and the susceptibility of
      benign prostatic hyperplasia: a meta-analysis.
AB  - Inconsistency between reported findings on the association of prostate specific
      antigen (PSA) gene -158G/A polymorphism with benign prostatic hyperplasia (BPH)
      susceptibility need a meta-analysis to obtain a more accurate conclusion. A
      systematic search was conducted in electronic databases for the collection of
      eligible studies on PSA -158G/A polymorphism and BPH susceptibility. Pooled odds
      ratios (ORs) and 95% confidence intervals (95% CIs) were then calculated. 7 case
      control studies with 758 cases and 752 controls were included into the present
      meta-analysis. The analysis results showed no significant relationship between
      PSA -158G/A polymorphism and BPH susceptibility in total analysis. Interestingly,
      after subgroup analyses based on ethnicity and source of control, the
      polymorphism reduced the susceptibility of BPH in Caucasian group (AA vs. GG:
      OR=0.47, 95% CI=0.25-0.89; allele A vs. allele G: OR=0.68, 95% CI=0.49-0.93), but
      it increased the disease susceptibility in Asian (AA vs. GG: OR=1.63, 95% CI=1.02
      2.60; allele A vs. allele G: OR=1.37, 95% CI=1.03-1.83) and population-based (AA
      vs. GG: OR=2.39, 95% CI=1.07-5.38; allele A vs. allele G: OR=1.83, 95% CI=1.26
      2.65) groups. PSA-158G/A polymorphism may be an inhibitor to the incidence of BPH
      in Caucasians, but it is likely to be a susceptible factor in Asians.

PMID- 28430621
TI  - Lymphovascular invasion is a high risk factor for stage I/II colorectal cancer: a
      systematic review and meta-analysis.
AB  - The prognostic value of lymphovascular invasion (LVI) in stage I/II colorectal
      cancer (CRC) does not reach a consensus. To systematically assess prognostic
      significance of LVI, databases of PubMed, Web of Science, and Embase were
      searched from inception up to 10 Dec 2016. The pooled hazard ratio (HR) and 95%
      confidence intervals (CI) were used to determine the prognostic effects. Nineteen
      relevant studies including 9881 total patients were enrolled. Our results showed
      that LVI is significantly associated with poor prognosis in overall survival (OS)
      (HR=2.15, 95 % CI=1.72-2.68, P < 0.01) and disease-free survival (DFS) (HR=1.73,
      95% CI=1.50-1.99, P < 0.01), which is similar in stage II patients. Further
      subgroup analysis revealed that the significance of the association between LVI
      and worse prognosis in CRC patients is not affected by below factors, including
      geographic setting, LVI positive rate, treatment, tumor site, and quality of the
      study. The current meta-analysis suggests that LVI may be a poor prognostic
      factor for stage I/II CRC patients.

PMID- 28430622
TI  - Serious adverse events of cell therapy for respiratory diseases: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Cell therapy holds the most promising for acute and chronic
      deleterious respiratory diseases. However, the safety and tolerance for lung
      disorders are controversy. METHODS: We undertook a systematic review and meta
      analyses of all 23 clinical studies of cell therapy. The outcomes were odds ratio
      (OR), risk difference (RD), Peto OR, relative risk, and mean difference of
      serious adverse events. RESULTS: 342 systemic infusions and 57 bronchial
      instillations (204 recipients) of cells were analyzed for acute respiratory
      distress syndrome (ARDS), bronchopulmonary dysplasia, pulmonary arterial
      hypertension, silicosis, sarcoidosis, extensively drug-resistant tuberculosis,
      chronic obstructive pulmonary diseases (COPD), and idiopathic pulmonary fibrosis.
      The frequency of death in adults from any causes was 71 and 177 per 1,000 for
      cell therapy and controls, respectively, with an OR of 0.31 (95% CI: 0.03, 3.76)
      and RD of -0.22 (95% CI: -0.53, 0.09). No significant difference was found for
      ARDS and COPD. The frequency of deaths and non-fatal serious adverse events of 17
      open studies were similar to those of randomized controlled trials. Moreover,
      serious adverse events of allogenic cells were greater than autologous
      preparations, as shown by frequency, OR and RD. CONCLUSIONS: We conclude that
      either infusion or instillation of mesenchymal stem stromal or progenitor cells
      are well tolerated without serious adverse events causally related to cell
      treatment. Cell therapy has not been associated with significant changes in
      spirometry, immune function, cardiovascular activity, and the quality of life.

PMID- 28430623
TI  - Clinical efficacy of icotinib in lung cancer patients with different EGFR
      mutation status: a meta-analysis.
AB  - Icotinib is a novel and the third listed epidermal growth factor receptor
      tyrosine kinase inhibitors (EGFR-TKIs), which exerts a good anti-tumor efficacy
      on non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs has been shown
      to be associated with the EGFR mutation status, especially exon 19 deletion
      (19Del) and exon 21 L858R mutation. Therefore, a meta-analysis was performed to
      assess the efficacy of icotinib in NSCLC patients harboring EGFR mutations (19Del
      or L858R) and wild type (19Del and L858R loci wild type). A total of 24 studies
      were included for comparing the objective response rate (ORR) in the EGFR wild
      type and mutant patients treated with icotinib. The ORRs of EGFR mutant patients
      (19Del or L858R) are better than those of EGFR wild type patients (OR = 7.03(5.09
      9.71), P < 0.00001). The pooling ORs from 21 studies on the disease control rate
      (DCR) in EGFR mutant patients are better than those of EGFR wild type patients
      (OR = 10.54(5.72-19.43), P < 0.00001). Moreover, the ORRs of EGFR 19Del patients
      are better than those of EGFR L858R patients after pooling ORs of 12 studies (OR
      = 2.04(1.12-3.73), P = 0.019). However, there was no significant difference on
      DCRs of EGFR 19Del patients and those of EGFR L858R patients (OR = 2.01(0.94
      4.32), P = 0.072). Our findings indicated that compared with EGFR wild type
      patients, EGFR mutant patients have better ORRs and DCRs after icotinib
      treatment; EGFR 19Del patients treated with icotinib have better ORRs than EGFR
      L858R patients. EGFR mutation status is a useful biomarker for the evaluation of
      icotinib efficacy in NSCLC patients.

PMID- 28430624
TI  - Photosensitizers in prostate cancer therapy.
AB  - The search for new therapeutics for the treatment of prostate cancer is ongoing
      with a focus on the balance between the harms and benefits of treatment. New
      therapies are being constantly developed to offer treatments similar to radical
      therapies, with limited side effects. Photodynamic therapy (PDT) is a promising
      strategy in delivering focal treatment in primary as well as post radiotherapy
      prostate cancer. PDT involves activation of a photosensitizer (PS) by appropriate
      wavelength of light, generating transient levels of reactive oxygen species
      (ROS). Several photosensitizers have been developed with a focus on treating
      prostate cancer like mTHPC, motexafin lutetium, padoporfin and so on. This
      article will review newly developed photosensitizers under clinical trials for
      the treatment of prostate cancer, along with the potential advantages and
      disadvantages in delivering focal therapy.

PMID- 28430625
TI  - MiR-766 induces p53 accumulation and G2/M arrest by directly targeting MDM4.
AB  - p53, a transcription factor that participates in multiple cellular functions, is
      considered the most important tumor suppressor. Previous evidence suggests that
      post-transcriptional deregulation of p53 by microRNAs contributes to
      tumorigenesis, tumor progression and therapeutic resistance. In the present
      study, we found that the microRNA miR-766 was aberrantly expressed in breast
      cancer, and that over-expression of miR-766 caused accumulation of wild-type p53
      protein in multiple cancer cell lines. Supporting its role in the p53 signalling
      pathway, miR-766 decreased cell proliferation and colony formation in several
      cancer cell lines, and cell cycle analyses revealed that miR-766 causes G2
      arrest. At a mechanistic level, we demonstrate that miR-766 enhances p53
      signalling by directly targeting MDM4, an oncogene and negative regulator of p53.
      Analysis of clinical genomic data from multiple cancer types supports the
      relevance of miR-766 in p53 signalling. Collectively, our study demonstrates that
      miR-766 can function as a novel tumor suppressor by enhancing p53 signalling.

PMID- 28430626
TI  - Expression of PD-L1 and prognosis in breast cancer: a meta-analysis.
AB  - The associations between programmed cell death ligand 1 (PD-L1) and the prognosis
      of various cancers have always been a research topic of considerable interest.
      However, the prognostic value of PD-L1 in breast cancer patients remains a
      controversial subject. We aimed to assess the association between PD-L1 protein
      expression and clinicopathological features and the impact of this relationship
      on breast cancer survival. We performed a systematic search of the PubMed,
      EMBASE, and Cochrane Library databases to determine the correlations among PD-L1
      expression, clinicopathological features and overall survival (OS). A total of 5
      studies containing 2,546 cases were included in the analysis. The combined hazard
      ratio (HR) and its 95% confidence interval (CI) for OS were 1.76 (95% CI 1.09
      2.82; P=0.02) for patients with tumors exhibiting PD-L1 overexpression. The
      pooled odds ratios (ORs) indicated that PD-L1 expression was associated with
      positive lymph node metastasis, higher histological grades, estrogen receptor
      (ER)-negativity, and triple-negative breast cancer (TNBC). Our findings indicate
      that PD-L1 expression is a promising biomarker for the prognosis of breast
      cancer, and may be helpful to clinicians aiming to select the appropriate
      immunotherapy for breast cancer.

PMID- 28430627
TI  - The long non-coding RNA H19 promotes cardiomyocyte apoptosis in dilated
      cardiomyopathy.
AB  - In the previous study, we generated a rat model of dilated cardiomyopathy (DCM)
      induced by adriamycin and found that the expression of lncRNA H19 was
      significantly upregulated in myocardial tissue. The present study was aimed to
      investigate the potential role of H19 in the pathogenesis of adriamycin-induced
      DCM. H19 knockdown in the myocardium of DCM rats attenuated cardiomyocyte
      apoptosis and improved left ventricular structure and function. Adriamycin
      treatment was associated with elevated H19 and miR-675 expression and increased
      apoptosis in neonatal cardiomyocytes. Enforced expression of miR-675 was found to
      induce apoptosis in cardiomyocytes with adriamycin treatment and H19-siRNA
      transfection. The 3'-untranslated region of PA2G4 was cloned downstream of a
      luciferase reporter construct and cotransfected into HEK293 cells with miR-675
      mimic. The results of luciferase assay showed that PA2G4 was a direct target of
      miR-675. The expression of PA2G4 was reduced in cardiomyocytes transfected with
      miR-675 mimic. Moreover, H19 knockdown was found to increase PA2G4 expression and
      suppress apoptosis in cardiomyocytes exposed to adriamycin. In conclusion, our
      study suggests that H19/miR-675 axis is involved in the promotion of
      cardiomyocyte apoptosis by targeting PA2G4, which may provide a new therapeutic
      strategy for the treatment of adriamycin-induced DCM.

PMID- 28430629
TI  - Vascular endothelial growth factor A polymorphisms are associated with increased
      risk of coronary heart disease: a meta-analysis.
AB  - Coronary heart disease (CHD) is a common complex disease resulting from the
      interaction of multiple environmental and genetic factors. To assess the
      potential relationship of vascular endothelial growth factor (VEGFA) rs699947
      C>A, rs3025039 C>T and rs2010963 G>C polymorphisms with CHD risk, a comprehensive
      meta-analysis was conducted. A systematic search of EMBASE and PubMed online
      database for publications on VEGFA polymorphisms and risk of CHD was carried out.
      Crude Odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated
      to determine the association. A total of ten publications including 22 trails
      involving 2097 cases and 2867 controls were included in our pooled analysis.
      Overall, results of the present meta-analysis demonstrated a significant
      association between VEGFA rs699947 C>A polymorphism and an increased risk of CHD.
      After stratifying by ethnicity and CHD type, the association was also obtained. A
      significant association between VEGFA rs3025039 C>T polymorphism and risk of CHD
      was also found. For VEGFA rs2010963 G>C polymorphism, the polymorphism was
      associated with MI risk. In conclusion, our findings suggest that VEGFA rs699947
      C>A, rs3025039 C>T and rs2010963 G>C polymorphisms are risk factors for CHD. In
      the future, large sample size and well-designed epidemiologic studies are needed
      to confirm these conclusions.

PMID- 28430634
TI  - Outcomes of microwave ablation for hepatocellular carcinoma adjacent to large
      vessels: a propensity score analysis.
AB  - The aim of this study was to retrospectively compare the long-term efficacy of MW
      ablation as a curative therapy for hepatocellular carcinoma(HCC) adjacent to
      large vessels(>=3 mm) with that in safe location. Between 2010 and 2016, 406
      patients diagnosed with early-stage HCC at Chinese PLA general hospital were
      enrolled. One-to-one matched pairs between the vessel group and the safe group
      were generated using propensity score matching. The associations of treatment
      strategy with overall survival and local tumor progression were determined by Cox
      regression. Before matching, 113 patients were classified into the vessel group
      and 293 patients were classified into the vessel group. The patients in the
      vessel group were more frequently classified as larger tumor size (P<0.05) and
      higher AFP level (P<0.05) than patients in the safe group. After propensity score
      matching, 113 pairs of well-matched HCC patients were selected from different
      treatment groups. No significant differences were found in local tumor
      progression, overall survival and complication rates for MW ablation as a first
      line treatment for the early-stage HCC between two groups. In conclusion, MW
      ablation provides an effective and safe way to treat early-stage HCC adjacent to
      large vessels.

PMID- 28430630
TI  - Estrogen and androgen-converting enzymes 17beta-hydroxysteroid dehydrogenase and
      their involvement in cancer: with a special focus on 17beta-hydroxysteroid
      dehydrogenase type 1, 2, and breast cancer.
AB  - Sex steroid hormones such as estrogens and androgens are involved in the
      development and differentiation of the breast tissue. The activity and
      concentration of sex steroids is determined by the availability from the
      circulation, and on local conversion. This conversion is primarily mediated by
      aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenases. In
      postmenopausal women, this is the primary source of estrogens in the breast. Up
      to 70-80% of all breast cancers express the estrogen receptor-alpha, responsible
      for promoting the growth of the tissue. Further, 60-80% express the androgen
      receptor, which has been shown to have tissue protective effects in estrogen
      receptor positive breast cancer, and a more ambiguous response in estrogen
      receptor negative breast cancers. In this review, we summarize the function and
      clinical relevance in cancer for 17beta-hydroxysteroid dehydrogenases 1, which
      facilitates the reduction of estrone to estradiol, dehydroepiandrosterone to
      androstendiol and dihydrotestosterone to 3alpha- and 3beta-diol as well as 17beta
      hydroxysteroid dehydrogenases 2 which mediates the oxidation of estradiol to
      estrone, testosterone to androstenedione and androstendiol to
      dehydroepiandrosterone. The expression of 17beta-hydroxysteroid dehydrogenases 1
      and 2 alone and in combination has been shown to predict patient outcome, and
      inhibition of 17beta-hydroxysteroid dehydrogenases 1 has been proposed to be a
      prime candidate for inhibition in patients who develop aromatase inhibitor
      resistance or in combination with aromatase inhibitors as a first line treatment.
      Here we review the status of inhibitors against 17beta-hydroxysteroid
      dehydrogenases 1. In addition, we review the involvement of 17beta-hydroxysteroid
      dehydrogenases 4, 5, 7, and 14 in breast cancer.

PMID- 28430635
TI  - Unsuccessful mitosis in multicellular tumour spheroids.
AB  - Multicellular spheroids are very attractive models in oncology because they mimic
      the 3D organization of the tumour cells with their microenvironment. We show here
      using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and
      cervical cancer HeLa), that when the cells are growing as spheroids the frequency
      of binucleated cells is augmented as occurs in some human tumours.We therefore
      describe mitosis in multicellular spheroids by following mitotic markers and by
      time-lapse experiments. Chromosomes alignment appears to be correct on the
      metaphasic plate and the passenger complex is well localized on centromere.
      Moreover aurora kinases are fully active and histone H3 is phosphorylated on Ser
      10. Consequently, the mitotic spindle checkpoint is satisfied and, anaphase
      proceeds as illustrated by the transfer of survivin on the spindle and by the
      segregation of the two lots of chromosomes. However, the segregation plane is not
      well defined and oscillations of the dividing cells are observed. Finally,
      cytokinesis fails and the absence of separation of the two daughter cells gives
      rise to binucleated cells.Division orientation is specified during interphase and
      persists throughout mitosis. Our data indicate that the cancer cells, in
      multicellular spheroids, lose their ability to regulate their orientation, a
      feature commonly encountered in tumours.Moreover, multicellular spheroid
      expansion is still sensitive to mitotic drugs as pactlitaxel and aurora kinase
      inhibitors. The spheroids thus represent a highly relevant model for studying
      drug efficiency in tumours.

PMID- 28430636
TI  - Exploring the role of paraoxonase-2 in bladder cancer: analyses performed on
      tissue samples, urines and cell cultures.
AB  - The enzyme paraoxonase-2 (PON2) is ubiquitously expressed and exerts its
      antiapoptotic and antioxidative functions in several intracellular
      compartments.The aim of this study is to investigate the role of PON2 in bladder
      cancer (BC). The expression levels of PON2 in paired tumor and normal bladder
      tissue samples and in urinary exfoliated cells from patients affected with BC and
      healthy donors were evaluated. Moreover, the effect of PON2 overexpression on
      tumor cell proliferation and susceptibility to oxidative stress was investigated
      in human bladder cancer cell line T24.Our results showed that PON2 expression
      levels were significantly higher in BC compared with non-tumor tissue. In urinary
      exfoliated cells from BC patients, PON2 mRNA levels showed an inverse correlation
      with tumor stage (pT). Moreover, PON2 overexpression in T24 cells led to a
      significant increase in tumor cell proliferation and resistance to oxidative
      stress.The results obtained showed that PON2 could represent a molecular
      biomarker for bladder cancer and suggest a potential role of the enzyme as a
      prognostic factor for this neoplasm.

PMID- 28430637
TI  - Clinical utility of circulating cell-free Epstein-Barr virus DNA in patients with
      gastric cancer.
AB  - Recent comprehensive molecular subtyping of gastric cancer (GC) identified
      Epstein-Barr virus (EBV)-positive tumors as a subtype with distinct salient
      molecular and clinical features. In this study, we aimed to determine the
      potential utility of circulating cell-free EBV DNA as a biomarker for the
      detection and/or monitoring of therapeutic response in patients with EBV
      associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA
      component H1 ratios (EBV ratios) in the GC tumors and plasma samples were
      determined by quantitative real-time polymerase chain reaction in 153 patients
      with GC, including 14 patients with EBVaGC diagnosed by the conventional method.
      Circulating cell-free EBV DNA was detected in 14 patients with GC: the
      sensitivity and specificity of detection were 71.4% (10/14) and 97.1% (135/139),
      respectively. Plasma EBV ratios were significantly correlated with the size of
      EBVaGC tumors, and the plasma EBV DNA detected before surgery in EBVaGC cases
      disappeared after surgery. Patients with EBVaGC may have a better prognosis, but
      circulating cell-free EBV DNA had no or little impact on prognosis. In addition,
      repeated assessment of the plasma EBV ratio in EBVaGC showed a decrease and
      increase in plasma EBV DNA after treatment and during tumor
      progression/recurrence, respectively. These results suggest the potential utility
      of circulating cell-free DNA to reveal EBV DNA for the identification of the
      EBVaGC subtype and/or for real-time monitoring of tumor progression as well as
      treatment response in patients with EBVaGC.

PMID- 28430638
TI  - Adjuvant celecoxib and lanreotide following transarterial chemoembolisation for
      unresectable hepatocellular carcinoma: a randomized pilot study.
AB  - Recurrence of hepatocellular carcinoma (HCC) after transarterial
      chemoembolisation (TACE) is common due to neoangiogenesis. Cyclooxygenase-2
      inhibitors and somatostatin analogues were reported to inhibit tumour
      angiogenesis. The pilot randomized controlled trial was aimed to prospectively
      evaluate the protocol of TACE combined with celecoxib and lanreotide (TACE+C+L)
      in patients with unresectable and advanced HCC. A total of 71 patients with HCC
      were enrolled and randomly assigned to either TACE (n=35) or TACE+C+L (n=36)
      group. Overall survival, disease control rate (DCR), and adverse events were
      assessed during a 3-year follow-up period. The median overall survival of the
      TACE+C+L group (15.0 months) was doubled compared to that of TACE group (7.5
      months), p = 0.012. DCR of the TACE+C+L group was significantly higher than that
      of the TACE group either at 6 months (72.2% vs 42.9%, p = 0.012) or at 12 months
      (61.1% vs 28.6%, p = 0.006). The median overall survivals (13 months vs 4.5
      months, p = 0.013) and DCR at 12 months (50% vs 13.6%, p = 0.008) of patients
      with advanced HCC in TACE+C+L groups were significantly higher than those in TACE
      group. No significant difference of adverse events was observed between the two
      groups. The occurrence of post-embolisation syndrome in TACE+C+L group was
      significantly lower than that in TACE group (16.7% vs 60.0%, p = 0.001). In
      conclusion, the regimen of TACE+C+L prolonged overall survival, enhanced tumour
      response, reduced post-embolisation syndrome and was well-tolerable in the
      patients with unresectable HCC. It may be more beneficial for advanced HCC.

PMID- 28430639
TI  - Should surgery be conducted for small nonfunctioning pancreatic neuroendocrine
      tumors: a systemic review.
AB  - BACKGROUND: The incidence of nonfunctioning pancreatic neuroendocrine tumors
      smaller than 2cm has increased remarkably in the last two decades. Controversies
      exist regarding whether surgery should be conducted for this group of tumors.
      METHODS: MEDLINE, EMBASE and CENTRAL were search until 2017/01/17. Studies with
      comparative results between operation and observation group were included.
      Primary outcomes were overall survival and disease specific survival. Secondary
      outcomes were disease progression and surgical death and complications. RESULTS:
      6 studies with a total of 1861 patients were identified. No randomized controlled
      trials were found. Survival rate was high (97-100%) and no patients died because
      of the disease in 5 of the 6 studies, with no difference between operation and
      observation group. Disease progression was compared in 3 of the 6 studies. 2
      studies reported minimal disease progression (0-3.5%) and no significant
      difference between operation and observation group. Perioperative deaths were
      rare (0-3%), but complications were common (33-46%). None of the 46 patients who
      crossed over form observation to operation group had disease recurrence after
      resection. CONCLUSION: Small NF-PNETs without distant metastasis, lymph node
      metastasis and local invasion on imaging studies can be observed without increase
      in death and disease progression.

PMID- 28430640
TI  - Epithelial-mesenchymal transition in prostate cancer: an overview.
AB  - Prostate cancer is a main urological disease associated with significant
      morbidity and mortality. Radical prostatectomy and radiotherapy are potentially
      curative for localized prostate cancer, while androgen deprivation therapy is the
      initial systemic therapy for metastatic prostate disease. However, despite
      temporary response, most patients relapse and evolve into castration resistant
      cancer.Epithelial-mesenchymal transition (EMT) is a complex gradual process that
      occurs during embryonic development and/or tumor progression. During this
      process, cells lose their epithelial characteristics and acquire mesenchymal
      features. Increasing evidences indicate that EMT promotes prostate cancer
      metastatic progression and it is closely correlated with increased stemness and
      drug resistance.In this review, we discuss the main molecular events that
      directly or indirectly govern the EMT program in prostate cancer, in order to
      better define the role and the mechanisms underlying this process in prostate
      cancer progression and therapeutic resistance.

PMID- 28430641
TI  - The regulation of beta-catenin activity and function in cancer: therapeutic
      opportunities.
AB  - Wnt/beta-catenin signaling is an evolutionarily conserved and versatile pathway
      that is known to be involved in embryonic development, tissue homeostasis and a
      wide variety of human diseases. Aberrant activation of this pathway gives rise to
      the accumulation of beta-catenin in the nucleus and promotes the transcription of
      many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to
      carcinogenesis and tumor progression of several cancers, including colon cancer,
      hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer. beta
      Catenin is a pivotal component of the Wnt signaling pathway and it is tightly
      regulated at three hierarchical levels: protein stability, subcellular
      localization and transcriptional activity. Uncovering the regulatory mechanisms
      of beta-catenin will provide new insights into the pathogenesis of cancer and
      other diseases, as well as new therapeutic strategies against these diseases. In
      this review we dissect the concrete regulatory mechanisms of beta-catenin from
      three aspects mentioned above. Then we focus on the role of beta-catenin in
      cancer initiation, progression, dormancy, immunity and cancer stem cell
      maintenance. At last, we summarize the recent progress in the development of
      agents for the pharmacological modulation of beta-catenin activity in cancer
      therapy.

PMID- 28430643
TI  - Lymph node status as a prognostic factor after palliative resection of primary
      tumor for patients with metastatic colorectal cancer.
AB  - Lymph node (LN) status is one of the most important predictors for M0 colorectal
      cancer patients. However, its clinical impact on stage IV colorectal cancer
      remains unclear. The study aimed to explore the prognostic value of LN status
      after palliative resection of primary tumor for patients with metastatic
      colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance,
      Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer
      Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER
      database. X-tile program was adopted to identify 2 and 10 as optimal cutoff
      values for negative lymph node (NLN) count to divide patients into 3 subgroups of
      high, middle and low risk of cancer related death. N stage and NLN count were
      verified as independent prognostic factors in multivariate analyses of patients
      in whole cohort and in subgroup analyses of each N stage (P<0.05). Validation of
      FUSCC cohort of patients demonstrated that metastatic tumor burden (P = 0.042),
      NLN count (P = 0.039) and sequential chemotherapy (P = 0.040) were significant
      predictors of poorer CSS. Specifically, the prognosis of patients at stage N0 was
      significantly more favorable than that of patients at stage N2 (P = 0.038). In
      conclusion, primary tumor LN status was a strong predictor of CSS after
      palliative resection of metastatic colorectal cancer. Advanced N stage and small
      number of NLN were correlated with high risk of cancer related death after
      palliative resection of primary tumor.

PMID- 28430642
TI  - Immunocompetent mouse allograft models for development of therapies to target
      breast cancer metastasis.
AB  - Effective drug development to combat metastatic disease in breast cancer would be
      aided by the availability of well-characterized preclinical animal models that
      (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame,
      (c) have an intact immune system, and (d) capture some of the heterogeneity of
      the human disease. To address these issues, we have assembled a panel of twelve
      mouse mammary cancer cell lines that can metastasize efficiently on implantation
      into syngeneic immunocompetent hosts. Genomic characterization shows that more
      than half of the 30 most commonly mutated genes in human breast cancer are
      represented within the panel. Transcriptomically, most of the models fall into
      the luminal A or B intrinsic molecular subtypes, despite the predominance of an
      aggressive, poorly-differentiated or spindled histopathology in all models.
      Patterns of immune cell infiltration, proliferation rates, apoptosis and
      angiogenesis differed significantly among models. Inherent within-model
      variability of the metastatic phenotype mandates large cohort sizes for
      intervention studies but may also capture some relevant non-genetic sources of
      variability. The varied molecular and phenotypic characteristics of this expanded
      panel of models should aid in model selection for development of antimetastatic
      therapies in vivo, and serve as a useful platform for predictive biomarker
      identification.

PMID- 28430644
TI  - Red and processed meat consumption and gastric cancer risk: a systematic review
      and meta-analysis.
AB  - The associations between red and processed meat consumption and gastric cancer
      risk have remained inconclusive. We performed a systematic review and meta
      analysis to analyze these associations. We searched PubMed and EMBASE to identify
      studies published from inception through October 2016. Subtype analyses of
      gastric cancer (gastric cardia adenocarcinoma and gastric non-cardiac
      adenocarcinoma) and dose-response analyses were performed. We finally selected 42
      eligible studies. The summary relative risks of highest versus lowest consumption
      were positive for case-control studies with 1.67 (1.36-2.05) for red meat and
      1.76 (1.51-2.05) for processed meat, but negative for cohort studies with 1.14
      (0.97-1.34) for red meat and 1.23 (0.98-1.55) for processed meat. Subtype
      analyses of cohort studies suggested null results for gastric cardia
      adenocarcinoma (red meat, P = 0.79; processed meat, P = 0.89) and gastric non
      cardiac adenocarcinoma (red meat, P = 0.12; processed meat, P = 0.12). In
      conclusion, the present analysis suggested null results between red and processed
      meat consumption and gastric cancer risk in cohort studies, although case-control
      studies yielded positive associations. Further well-designed prospective studies
      are needed to validate these findings.

PMID- 28430646
TI  - Immunotherapeutic target expression on breast tumors can be amplified by hormone
      receptor antagonism: a novel strategy for enhancing efficacy of targeted
      immunotherapy.
AB  - Immunotherapy has historically been successful in highly antigenic tumors but has
      shown limited therapeutic efficacy in non-antigenic tumors such as breast
      cancers. Our previous studies in autoimmunity have demonstrated that increased
      antigen load within a tissue enhances immune reactivity against it. We therefore
      hypothesized that enhancing expression of target proteins on breast tumors can
      increase efficacy of targeted immunotherapy. We hypothesized that antagonism of
      the estrogen receptor (ER) can increase expression of targets that are hormonally
      regulated and facilitate enhanced tumor recognition by targeted immunotherapy. We
      used a lactation protein alpha-Lactalbumin, a known immunotherapeutic target on
      breast tumors, as our model target antigen. Enhancement of target protein
      expression in human and murine breast tumors was tested in vitro and in vivo by
      ER antagonism using clinically established ER modulators, Tamoxifen and
      Fulvestrant. We show that antagonism of the ER can induce a 2-3 fold increase in
      expression of target proteins on tumors leaving the normal breast tissue
      unaffected. Tumor progression studies in 4T1 tumor-bearing mice show that
      efficacy of adoptively transferred cell based targeted immunotherapy was enhanced
      by target antigen amplification resulting in significantly higher tumor
      inhibition. However, in spite of increased target expression, anti-tumor efficacy
      of direct immunization was not enhanced probably due to other limiting factors
      involved in the immune priming process. Our study provides a novel combinatorial
      clinical strategy for enhancing efficacy of immunotherapy not only on breast
      tumors but potentially also for other hormonally driven tumors such as those of
      the prostate, testis and ovary.

PMID- 28430645
TI  - Midkine promotes hepatocellular carcinoma metastasis by elevating anoikis
      resistance of circulating tumor cells.
AB  - Midkine is overexpressed in hepatocellular carcinoma (HCC) and plays a role in
      tumor progression, but less is known about its role in resistance of circulating
      tumor cells (CTCs) to anoikis which leading to recurrence and metastasis. The aim
      of the present study was to analyze whether midkine was associated with HCC
      progression with anoikis resistance. We found that cultured HCC cells were more
      resistant to anoikis, which paralleled midkine expression, and midkine treatment
      significantly inhibited anoikis in a dose-dependent manner. Furthermore, in in
      vitro and in vivo assays, knockdown of midkine resulted in significant
      sensitivity to anoikis, decreased cell survival and significantly decreased tumor
      occurrence rate. Patients with midkine-elevated HCC had higher CTC counts and
      less apoptotic CTCs, as well as significantly higher recurrence rate and shorter
      recurrence-free interval. To understand the molecular mechanism underlying the
      midkine with HCC progression, we performed in vitro and in vivo studies. We found
      that midkine plays an important role in enhancement of HCC cell resistance to
      anoikis, thereby promoting subsequent metastasis. Activation of PI3K/Akt/NF
      kappaB/TrkB signaling by midkine-activated anaplastic lymphomakinase (ALK) is
      responsible for anoikis resistance.

PMID- 28430647
TI  - PINK1 and Ataxin-2 as modifiers of growth.

PMID- 28430648
TI  - Radioimmunotherapy for CD133(+) colonic cancer stem cells inhibits tumor
      development in nude mice.
AB  - Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of
      tumor drug/radio-resistance or distant metastasis; therefore, it is essential to
      eliminate CSCs to cure cancer completely. The purpose of this study was to
      utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe
      whether this prevented tumor development, by assessing the maximum tolerated dose
      (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1
      monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with
      131I-AC133.1 mAb. For RIT trials, animals were randomly divided into 4 groups of
      6 per group, and injected with 131I-AC133.1 mAb (16.65 MBq/100 MUl), AC133.1 mAb
      (173.1 MUg/100 MUl), saline (100 MUl), or unrelated IgG1 as an isotype control.
      Iodine-131 was radiolabeled to AC133.1 mAb by conjugation with N-succinimidyl 3
      (tri-n-butylstannyl) benzoate. The MTD of HCT116 tumor-bearing nude mice was
      16.65 MBq. Both of the tumor volume doubling time and the survival time of the
      131I-AC133.1 mAb group were significant longer than other groups (P < 0.001).
      CD133 expression was assessed by flow cytometry. Protein levels of cancer stem
      like biomarkers (CD133, ALDH1, Lgr5, Vimentin, Snail1), and the proliferative
      rate of 131I-AC133.1 mAb group were lower than other groups (P<0.001); while its
      protein level of E-cadherin was higher than other groups. Furthermore, a large
      proportion of tumor necrosis was also observed in the 131I-AC133.1 mAb group,
      suggesting that RIT can destroy CSCs and effectively inhibit tumor development.

PMID- 28430661
TI  - The role of postoperative radiotherapy (PORT) in combined small cell lung cancer
      (C-SCLC).
AB  - PURPOSE: To explore the value of radiotherapy in C-SCLC patients, especially in
      those receiving a radical resection. RESULTS: The differences of survivals
      between the postoperative radiotherapy (PORT) and non-PORT groups were not
      statistically significant. But analyzing the benefits in subgroups, PORT
      significantly improved OS (p = 0.015), DFS (p = 0.026), LRFS (p = 0.008) and DMFS
      (p = 0.030) in stage III patients. For the patients with N2 stage, all survivals
      of the PORT group were also statistically significantly higher than non-PORT
      group (p = 0.018, 0.032, 0.008, 0.042). Patients with more than 10% of metastatic
      lymph nodes could get a significant benefit survivals by receiving PORT (p =
      0.033, 0.030, 0.025, 0.031). Having a systematic dissection of more than 17 lymph
      nodes was a subset which could get better OS and LRFS by receiving PORT (p =
      0.045, 0.048). METHODS: Between Jan. 2004 to Dec. 2012, fifty-five patients
      diagnosed as C-SCLC after complete surgical resection in our center were
      retrospectively analyzed. The overall survival (OS), disease free survival (DFS),
      loco-regional recurrence free survival (LRFS), and distant metastasis free
      survival (DMFS) were calculated by Kaplan-Meier method. CONCLUSIONS: PORT can
      significantly improve the survival of C-SCLC patients with resected pathological
      pN2 stage. For the patients with a large percent of metastatic lymph nodes, PORT
      can also improve survivals.

PMID- 28430662
TI  - Histone demethylase JMJD3 regulates CD11a expression through changes in histone
      H3K27 tri-methylation levels in CD4+ T cells of patients with systemic lupus
      erythematosus.
AB  - Aberrant CD11a overexpression in CD4+ T cells induces T cell auto-reactivity,
      which is an important factor for systemic lupus erythematosus (SLE) pathogenesis.
      Although many studies have focused on CD11a epigenetic regulation, little is
      known about histone methylation. JMJD3, as a histone demethylase, is capable of
      specifically removing the trimethyl group from the H3K27 lysine residue,
      triggering target gene activation. Here, we examined the expression and function
      of JMJD3 in CD4+ T cells from SLE patients. Significantly decreased H3K27me3
      levels and increased JMJD3 binding were detected within the ITGAL (CD11a)
      promoter locus in SLE CD4+ T cells compared with those in healthy CD4+ T cells.
      Moreover, overexpressing JMJD3 through the transfection of pcDNA3.1-JMJD3 into
      healthy donor CD4+ T cells increased JMJD3 enrichment and decreased H3K27me3
      enrichment within the ITGAL (CD11a) promoter and up-regulated CD11a expression,
      leading to T and B cell hyperactivity. Inhibition of JMJD3 via JMJD3-siRNA in SLE
      CD4+ T cells showed the opposite effects. These results demonstrated that histone
      demethylase JMJD3 regulates CD11a expression in lupus T cells by affecting the
      H3K27me3 levels in the ITGAL (CD11a) promoter region, and JMJD3 might thereby
      serve as a potential therapeutic target for SLE.

PMID- 28430663
TI  - Co-expression network analysis identified six hub genes in association with
      metastasis risk and prognosis in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) has a high incidence and mortality worldwide, and
      its carcinogenesis and progression are influenced by a complex network of gene
      interactions. A weighted gene co-expression network was constructed to identify
      gene modules associated with the clinical traits in HCC (n = 214). Among the 13
      modules, high correlation was only found between the red module and metastasis
      risk (classified by the HCC metastasis gene signature) (R2 = -0.74). Moreover, in
      the red module, 34 network hub genes for metastasis risk were identified, six of
      which (ABAT, AGXT, ALDH6A1, CYP4A11, DAO and EHHADH) were also hub nodes in the
      protein-protein interaction network of the module genes. Thus, a total of six hub
      genes were identified. In validation, all hub genes showed a negative correlation
      with the four-stage HCC progression (P for trend < 0.05) in the test set.
      Furthermore, in the training set, HCC samples with any hub gene lowly expressed
      demonstrated a higher recurrence rate and poorer survival rate (hazard ratios
      with 95% confidence intervals > 1). RNA-sequencing data of 142 HCC samples showed
      consistent results in the prognosis. Gene set enrichment analysis (GSEA)
      demonstrated that in the samples with any hub gene highly expressed, a total of
      24 functional gene sets were enriched, most of which focused on amino acid
      metabolism and oxidation. In conclusion, co-expression network analysis
      identified six hub genes in association with HCC metastasis risk and prognosis,
      which might improve the prognosis by influencing amino acid metabolism and
      oxidation.

PMID- 28430665
TI  - P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer.
AB  - In this study, we investigated purinergic receptor P2X7 and NACHT, LRR and PYD
      domains-containing protein 3 (NLRP3) inflammasome expressions, and their role in
      head and neck cancer. We found upregulation of purinergic receptor P2X7 and all
      NLRP3 inflammasome components in biopsied head and neck squamous cell carcinoma
      tissues. Similarly, the expression of purinergic receptor P2X7, apoptosis
      associated speck-like protein containing CARD, and pro-form caspase 1 in A253
      cells derived from epidermoid carcinoma were highly upregulated in comparison to
      normal Human Salivary Gland cell line. Active caspase-1 and its final product,
      active interleukin-1beta, both increased in primed A253 cells stimulated with
      purinergic receptor P2X7 agonists, while this elevated NLRP3 inflammasome
      activity was suppressed by purinergic receptor P2X7 antagonists. However, we
      observed none of these effects in Human Salivary Gland cells. Inhibition of both
      NLRP3 inflammasome and purinergic receptor P2X7 led to the significant cell death
      of primed A253 cells, but had no effect on the viability of primed HSG cells or
      the primary cultured human fibroblast cells. Furthermore, inhibition of either
      purinergic receptor P2X7 or NLRP3 inflammasome decreased invasiveness of A253,
      and this effect became more evident when both purinergic receptor P2X7 and NLRP3
      inflammasome were simultaneously blocked. Therefore, it is concluded that the
      purinergic receptor P2X7 and the activation of NLRP3 inflammasome play important
      roles in the survival and invasiveness of head and neck squamous cell carcinoma
      in humans.

PMID- 28430664
TI  - Identification of a novel PD-L1 positive solid tumor transplantable in HLA
      A*0201/DRB1*0101 transgenic mice.
AB  - HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study
      the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use
      and application of this mouse model in the field of antitumor immunotherapy, we
      described a tumor cell line generated from a naturally occurring tumor in A2/DR1
      mouse named SARC-L1. Histological and genes signature analysis supported the
      sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101
      expression, a very low expression of HLA-A*0201 molecules was found on these
      cells. Furthermore they also weakly but constitutively expressed the programmed
      death-ligand 1 (PD-L1). Interestingly both HLA-A*0201 and PD-L1 expressions can
      be increased on SARC-L1 after IFN-gamma exposure in vitro. We also obtained two
      genetically modified cell lines highly expressing either HLA-A*0201 or both HLA
      A*0201/ HLA-DRB1*0101 molecules referred as SARC-A2 and SARC-A2DR1 respectively.
      All the SARC-L1-derived cell lines induced aggressive subcutaneous tumors in
      A2DR1 mice in vivo. The analysis of SARC-L1 tumor microenvironment revealed a
      strong infiltration by T cells expressing inhibitory receptors such as PD-1 and
      TIM-3. Finally, we found that SARC-L1 is sensitive to several drugs commonly used
      to treat sarcoma and also susceptible to anti-PD-L1 monoclonal antibody therapy
      in vivo. Collectively, we described a novel syngeneic tumor model A2/DR1 mice
      that could be used as preclinical tool for the evaluation of antitumor
      immunotherapies.

PMID- 28430667
TI  - Enhanced thermal imaging of wound tissue for better clinical decision making.
AB  - : Infrared cameras are increasingly applied in clinical applications as they
      allow fast, inexpensive and non-contact temperature measurements. As abnormal
      heat distribution can indicate illness, infrared cameras have been applied in the
      prediction, diagnosis and monitoring of medical conditions. Current practices,
      however, often overlook the importance of emissivity when taking thermal
      measurements. The consensus is that human skin has an emissivity of 0.98 but this
      value varies between individuals, areas examined, and if the skin is damaged. In
      particular, further research should be conducted on the emissivity variations of
      wounds. OBJECTIVE: This research investigated the emissivity variation of chronic
      wounds and its effect on thermal measurements. Eleven patients with non-infected
      foot ulcers were recruited. Three non-diabetic wounds were also investigated in a
      clinical setting. APPROACH: A reflectance based method was used which involved
      alternating shades at different temperatures over the region of interest. Based
      on the change in the thermal images, emissivity was calculated at each pixel.
      MAIN RESULTS: Overall, it was found that the emissivity of wounds was similar or
      slightly higher to intact skin (range 0.01-0.03 higher with an average value of
      0.97  +/-  0.03), with lower values at wound edges (on average 0.02 lower than
      intact skin). Correcting for emissivity resulted in an average temperature
      difference of 0.83% in the thermal images. SIGNIFICANCE: Despite the similarity
      in emissivity, the difference between the original thermal image and the
      emissivity corrected thermal image in some cases was substantial. These
      differences could prove significant in clinical evaluations, indicating the need
      to incorporate emissivity measurement into standard protocol to ensure utmost
      accuracy.

PMID- 28430666
TI  - Myc-induced glutaminolysis bypasses HIF-driven glycolysis in hypoxic small cell
      lung carcinoma cells.
AB  - We previously demonstrated that small cell lung carcinoma (SCLC) cells lack HIF
      2alpha protein expression, whereas HIF-1alpha in these cells is expressed at both
      acute and prolonged hypoxia. Here we show that low HIF2A expression correlates
      with high expression of MYC genes. Knockdown of HIF1A expression had no or
      limited effect on cell survival and growth in vitro. Unexpectedly, hypoxic ATP
      levels were not affected by HIF-1alpha knockdown and SCLC cell viability did not
      decrease upon glucose deprivation. In line with these in vitro data, xenograft
      tumor-take and growth were not significantly affected by repressed HIF1A
      expression. Glutamine withdrawal drastically decreased SCLC cell proliferation
      and increased cell death at normoxia and hypoxia in a HIF-independent fashion and
      the dependence on glutaminolysis was linked to amplification of either MYC or
      MYCL. Downregulation of GLS expression, regulating the first step of the
      glutaminolysis pathway, in MYC/MYCL overexpressing SCLC cells resulted in both
      impaired growth and increased cell death. Our results suggest that MYC/MYCL
      overexpression in SCLC cells overrides the need of HIF-1 activity in response to
      hypoxia by inducing glutaminolysis and lipogenesis. Targeting the glutaminolysis
      pathway might hence be a novel approach to selectively kill MYC amplified SCLC
      cells in vivo.

PMID- 28430668
TI  - A turn-on fluorescent probe for endogenous formaldehyde in the endoplasmic
      reticulum of living cells.
AB  - As the simplest aldehyde compounds, formaldehyde (FA) is implicated in nervous
      system diseases and cancer. Endoplasmic reticulum is an organelle that plays
      important functions in living cells. Accordingly, the development of efficient
      methods for FA detection in the endoplasmic reticulum (ER) is of great biomedical
      importance. In this work, we developed the first ER-targeted fluorescent FA probe
      Na-FA-ER. The detection is based on the condensation reaction of the hydrazine
      group and FA to suppress the photo-induced electron transfer (PET) pathway,
      resulting in a fluorescence increase. The novel Na-FA-ER showed high sensitivity
      to FA. In addition, the Na-FA-ER enabled the bio-imaging of exogenous and
      endogenous FA in living HeLa cells. Most significantly, the new Na-FA-ER was
      employed to visualize the endogenous FA in the ER in living cells for the first
      time.

PMID- 28430669
TI  - Low previous cardiovascular risk of patients with ST-elevation myocardial
      infarction.
AB  - BACKGROUND: Myocardial infarction is frequently the initial form of presentation
      of coronary artery disease (CAD). Systemic Coronary Risk Estimation (SCORE) risk
      tables are used in primary prevention and provide an estimate of cardiovascular
      (CV) risk through known risk factors. The aim of this study was to evaluate the
      performance of the SCORE, calculated using data previous to the event, to
      estimate CV risk of a population of patients presenting with ST-elevation
      myocardial infarction (STEMI) as the first manifestation of CAD. METHODS AND
      RESULTS: From a prospective registry including 3056 patients with STEMI subjected
      to coronary angiography between 2004 and 2014, 1628 patients with STEMI as the
      first manifestation of CAD were included after the exclusion of patients with
      known CAD (n=748, 24.5%), patients with high-risk equivalents (n=930, 30.4%), and
      patients with normal coronaries (n=57, 1.87%). The individual risk profile was
      calculated using data previous to the event and patients were classified into
      three established subgroups: low risk (SCORE<5%; n=1162, 71.4%), high risk (SCORE
      5-10%; n=409, 25.1%), and very high risk (SCORE>=10%; n=57, 3.5%). CONCLUSION: In
      a population of patients with STEMI as the first manifestation of CAD, the CV
      risk stratification with the SCORE risk charts, if calculated before the event,
      would classify as low risk more than two-thirds of the patients (71.4%) and only
      3.5% would be classified as very high-risk patients. The high prevalence of low
      risk patients indicates the current challenge of CV risk stratification,
      underlying the need for additional tools in primary prevention to better identify
      patients at risk.

PMID- 28430670
TI  - Comparison between long-acting injectable aripiprazole versus paliperidone
      palmitate in the treatment of schizophrenia: systematic review and indirect
      treatment comparison.
AB  - We investigated the relative efficacy and tolerability of aripiprazole once
      monthly (AOM) versus paliperidone palmitate (PP) for treating schizophrenia.
      Extensive databases searches on short-term, placebo-controlled, randomized
      studies of AOM and PP were performed. Indirect treatment comparisons were
      performed between the two long-acting injectable antipsychotics (LAIAs). The
      primary efficacy endpoint was the mean change in the Positive and Negative
      Syndrome Scale total score from baseline between each LAIA and placebo. The
      effect sizes were mean differences and odds ratio (ORs) with 95% confidence
      intervals (CIs) for the primary efficacy endpoint and safety/tolerability between
      two LAIAs, respectively. Mean difference in the primary efficacy endpoint was
      significantly different, favouring AOM over PP (OR: -6.4; 95% CI: -11.402 to 
      1.358); sensitivity analyses and noninferiority test (AOM vs. PP) confirmed the
      primary results. The overall early dropout rate was not significantly different
      between AOM and PP (OR: 1.223; 95% CI: 0.737-2.03). However, there was a
      significant difference in the early dropout rate in terms of lack of efficacy
      favouring AOM over PP (OR: 0.394; 95% CI: 0.185-0.841). Within the context of the
      inherent limitations of the current analysis, our results may suggest that there
      may be relative advantages for AOM over PP in the short-term treatment of
      schizophrenia.

PMID- 28430671
TI  - Elevated Production of Nociceptive CC-chemokines and sE-selectin in Patients with
      Low Back Pain and the Effects of Spinal Manipulation: A Non-randomized Clinical
      Trial.
AB  - BACKGROUND: The involvement of inflammatory components in the pathophysiology of
      low back pain is poorly understood. It has been suggested that spinal
      manipulative therapy (SMT) may exert anti-inflammatory effects. PURPOSE: To
      determine the involvement of inflammation-associated chemokines (CC series) in
      the pathogenesis of non-specific low back pain and to evaluate the effect of SMT
      on that process. METHODS: Patients presenting with non-radicular, non-specific
      low back pain (minimum pain score 3 on 10 point visual analogue scale, VAS) were
      recruited according to stringent inclusion criteria. They were evaluated for
      appropriateness to treat using a high velocity low amplitude manipulative thrust
      (HVLT) in the lumbar-lumbosacral region. Blood samples were obtained at baseline
      and following the administration of a series of 6 HVLTs on alternate days over
      the period of two weeks. The in vitro levels of CC chemokines (CCL2, CCL3 and
      CCL4) production and plasma levels of an inflammatory biomarker, soluble E
      selectin, were determined at baseline and at the termination of treatments two
      weeks later. RESULTS: Compared with asymptomatic controls baseline production of
      all chemokines was significantly elevated in acute (P=0.004 - <0.0001), and that
      of CCL2 and CCL4 in chronic LBP patients (P<0.0001). Furthermore, CCL4 production
      was significantly higher (P<0.0001) in the acute versus chronic LBP group. sE
      selectin levels were significantly higher (P=0.003) in chronic but not in acute
      LBP patients. Following SMT, patient reported outcomes showed significant
      (P<0.0001) improvements in VAS and ODI scores. This was accompanied by a
      significant decline in CCL 3 production (P<0.0001) in both groups of patients.
      Change scores for CCL4 production differed significantly (P<0.0001) only for the
      acute LBP cohort, and no effect on the production of CCL2 or plasma sE-selectin
      levels was noted in either group. CONCLUSION: The production of chemotactic
      cytokines is significantly and protractedly elevated in LBP patients. Changes in
      chemokine production levels, which might be related to SMT, differ in the acute
      and chronic LBP patient cohorts.This is an open-access article distributed under
      the terms of the Creative Commons Attribution-Non Commercial-No Derivatives
      License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work
      provided it is properly cited. The work cannot be changed in any way or used
      commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.

PMID- 28430672
TI  - Lamotrigine Uses in Psychiatric Practice-Beyond Bipolar Prophylaxis a Hope or
      Hype?
AB  - BACKGROUND: Lamotrigine (LAM), an antiepileptic, with panoply of indications and
      uses in neurology, is FDA approved, in psychiatry, for bipolar prophylaxis. Apart
      from this indication, trend of its use in psychiatry is on the rise addressing a
      multitude of disorders. STUDY QUESTION: LAM remains one of only few psychotropic
      drugs with antiglutamate activity. This might render LAM a potential therapeutic
      option in treatment-resistant major psychiatric disorders. We reviewed LAM
      pharmacology and its diverse indications while examining the extant evidence.
      METHODS: EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane
      Database of Systemic Reviews were searched for all relevant studies up to date of
      June 2016. RESULTS: Sound evidence supports use of LAM for acute bipolar
      depression and prophylaxis, treatment-resistant schizophrenia, treatment
      resistant obsessive-compulsive disorder, posttraumatic stress disorder,
      depersonalization disorder, and affective dysregulation and behavioral dyscontrol
      domains of borderline personality disorder. Less compelling evidence is present
      for use in behavioral and psychological symptoms of dementia and neuropsychiatric
      sequelae of traumatic brain injury. No evidence supports use in autism spectrum
      disorder or acute unipolar depression. CONCLUSIONS: LAM is an important addition
      to the psychopharmacological armamentarium. Level of evidence supporting the use
      of LAM in off-label indications is highly variable, and hence, sound clinical
      judgment is necessary for its proper use and placement in real-life psychiatric
      practice and psychopharmacotherapy algorithms.

PMID- 28430674
TI  - Continuous EEG in Pediatric Critical Care: Yield and Efficiency of Seizure
      Detection.
AB  - PURPOSE: Our goal was to define the duration of continuous EEG (cEEG) monitoring
      needed to adequately capture electrographic seizures and EEG status epilepticus
      in the pediatric intensive care unit using clinical and background EEG features.
      METHODS: Retrospective study of patients aged 1 month to 21 years admitted to a
      tertiary pediatric intensive care unit and undergoing cEEG (>3 hours). Clinical
      data collected included admission diagnosis, EEG background features, and time
      variables including time to first seizure after initiation of cEEG. RESULTS: Four
      hundred fourteen patients aged 4.2 (0.75-11.3) years (median, interquartile
      range) were included. With a median duration of 21 (16-42.2) hours of cEEG
      monitoring, we identified electrographic seizure or EEG status epilepticus in 25%
      of subjects. We identified three features that could improve the efficiency of
      cEEG resources and provide a decision-making framework: (1) clinical history of
      acute encephalopathy is not predictive of detecting electrographic seizure or EEG
      status epilepticus, whereas a history of status epilepticus or seizures is; (2)
      normal EEG background or absence of epileptiform discharges in the initial 24
      hours of recording informs the decision to discontinue cEEG; (3) failure to
      record electrographic ictal events within the first 4 to 6 hours of monitoring
      may be sufficient to predict the absence of subsequent ictal events. CONCLUSIONS:
      Individualized monitoring plans are necessary to increase seizure detection yield
      while improving resource utilization. A strategy using information from the
      clinical history, initial EEG background, and the first 4 to 6 hours of recording
      may be effective in determining the necessary duration of cEEG monitoring in the
      pediatric intensive care unit.

PMID- 28430673
TI  - Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and
      Clinical Implications.
AB  - BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia, meningitis,
      sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased
      resistance to multiple classes of antibiotics. STUDY DESIGN: Systematic
      literature review of prevalence, mechanisms, and clinical implications in S.
      pneumoniae resistance. AREAS OF UNCERTAINTY: Since S. pneumoniae resistance to
      penicillin was first reported with subsequent development of resistance to other
      classes of drugs, selection of appropriate antibiotic treatment is challenging.
      DATA SOURCES: We searched PubMed (English language) for citations to antibiotic
      resistance in S. pneumoniae published before March 1, 2016. RESULTS: We present a
      review of S. pneumoniae resistance to beta-lactams, macrolides, lincosamides,
      fluoroquinolones, tetracyclines, and trimethoprim-sulfamethoxazole (TMP-SMX).
      There has been a steady decline in susceptibility of S. pneumoniae to commonly
      used beta-lactams. Phenotypic expression of penicillin resistance occurs as a
      result of a genetic structural modification in penicillin-binding proteins.
      Between 20% and 40% of S. pneumoniae isolates are resistant to macrolides.
      Macrolide resistance mechanisms include ribosomal target site alteration,
      alteration in antibiotic transport, and modification of the antibiotic.
      Approximately 22% of S. pneumoniae isolates are resistant to clindamycin. Similar
      to macrolide resistance, clindamycin involves a target site alteration. The
      prevalence of fluoroquinolone resistance is low, although increasing. S.
      pneumoniae resistance to fluoroquinolones occurs by accumulated mutations within
      the bacterial genome, increased efflux, or acquisition of plasmid-encoded genes.
      S. pneumoniae resistance has also increased for the tetracyclines. The primary
      mechanism is mediated by 2 genes that confer ribosomal protection. The prevalence
      of TMP-SMX resistance is around 35%. As with fluoroquinolones, resistance to TMP
      SMX is secondary to mutations in the bacterial genome. CONCLUSIONS: Effective
      treatment of resistant S. pneumoniae is a growing concern. New classes of drugs,
      newer formulations of older drugs, combination antibiotic therapy, nonantibiotic
      modalities, better oversight of antibiotic usage, and enhanced preventive
      measures hold promise.

PMID- 28430675
TI  - Identifying Risk Factors Leading to Unanticipated Postoperative Readmission.
AB  - INTRODUCTION: Unanticipated postoperative readmissions are a grading metric
      directly linked to both the quality of patient care and physician reimbursement.
      However, little data exist to define factors responsible for these readmissions
      in the plastic surgery patient population. This study aims to identify patient
      risk factors contributing to unanticipated postoperative readmissions to optimize
      perioperative patient care and mitigate negative financial impact upon providers.
      METHODS: We present an institutional review board-approved study retrospective
      review of 819 plastic surgery patients undergoing operative procedures performed
      at our institution between January 1, 2013, and December 31, 2014. All
      unanticipated readmissions within 30 days of an operation were identified and
      subjected to statistical analysis in an effort to determine whether these
      readmissions were associated with identifiable patient risk factors. RESULTS: One
      hundred forty-nine (18.1%) of the 819 investigated patients underwent
      readmission, reoperation, or both within 30 postoperative days. Seventy-four (9%)
      patients required hospital readmission, alone; 55 (6.7%) underwent readmission
      with operative intervention; and 20 (2.4%) required outpatient operative
      intervention without readmission. Readmitted patients were significantly more
      likely to have a positive smoking history (P = 0.009), hypertension (P = 0.0008),
      congestive heart failure (P = 0.0015), chronic obstructive pulmonary disease (P =
      0.023), a higher mean age (P = 0.0001), and a higher Charlson Comorbidity Score
      (P = 0.0001). CONCLUSIONS: These results identify risk factors associated with
      unanticipated postoperative readmissions specific to a plastic surgery patient
      population. With this information, practitioners can allocate appropriate
      perioperative resources and planning for patients at increased risk for
      readmission, thereby improving delivery of patient care and satisfying quality
      metrics linked to practitioner reimbursement.

PMID- 28430676
TI  - A Biomimetic Alternative to Synthetic Hydroxyapatite: "Boron-Containing Bone-Like
      Hydroxyapatite" Precipitated From Simulated Body Fluid.
AB  - BACKGROUND: Biological hydroxyapatite (HA), has several mechanical and physical
      advantages over the commercially available synthetic apatite (CAP-HA). The aim of
      this in vivo study was to investigate the effect of osteoinductive "bone-like
      hydroxyapatite" obtained from simulated body fluid (SBF) combined with
      osteoinductive "boron" (B) on bone healing. MATERIALS: Bone like
      nanohydroxyapatite (SBF-HA) was precipitated from 10* simulated body fluid
      (10*SBF). Thirty Sprague-Dawley rats were randomly divided into 5 experimental
      groups (n = 6 each). The groups were involving blank defect, chitosan, SBF-HA,
      SBF-HA/B, and CAP-HA. Two biparietal round critical sized bone defect was created
      using a dental burr. The rats were sacrificed respectively at the end of second
      and fourth months after surgery and their calvarium were harvested for further
      macroscopic, microtomographic, and histologic evaluation. RESULTS: The SBF-HA/B
      group demonstrated the highest mineralized matrix formation rates (30.69 +/- 3.73
      for the second month, 62.68 +/- 7.03 for the fourth month) and was significantly
      higher than SBF-HA and the CAP-HA groups. The SBF-HA/B group demonstrated the
      highest mineralized matrix formation rates (30.69 +/- 3.73 for the second month,
      62.68 +/- 7.03 for the fourth month) and was significantly higher than SBF-HA and
      the CAP-HA groups. In means of bone defect repair histologically, the highest
      result was observed in the SBF-HA/B group (P < 0.001). CONCLUSIONS: The "bone
      like hydroxapatite" obtained from simulated body fluid is worth attention when
      both its beneficial effects on bone healing and its biological behavior is taken
      in consideration for further bone tissue engineering studies. It appears to be a
      potential alternative to the commercially available hydroxyapatite samples.

PMID- 28430677
TI  - Changes in Hair Mercury Levels Among Women of Child-Bearing Age Following an
      Educational Intervention.
AB  - OBJECTIVE: Describe mercury exposures among women of childbearing age before and
      after an educational intervention. METHODS: Women age 18 to 45 were recruited to
      participate in an educational intervention concerning fish consumption. Fish
      consumption habits and total mercury concentration in hair were assessed pre- and
      post-intervention. Regression models examined associations between mercury, fish
      consumption, and demographics. RESULTS: Overall, 234 women completed the study.
      On average, mercury concentrations increased by 0.01 ppm (parts per million)
      following the intervention, despite declines in fish consumption; however, women
      in the 90th percentile for mercury at baseline decreased concentrations
      significantly while maintaining high rates of fish consumption. Mercury
      concentrations were positively correlated with fish consumption and certain
      demographic characteristics. CONCLUSIONS: The intervention reached individuals
      most at-risk. Healthcare providers should discuss fish consumption habits with
      women to encourage consumption of low-risk fish, and identify women needing
      education and counseling.

PMID- 28430679
TI  - Cervicovaginal Levels of Human beta-Defensin 1, 2, 3, and 4 of Reproductive-Aged
      Women With Chlamydia trachomatis Infection.
AB  - OBJECTIVE: This study included women attending primary health care units in
      Botucatu, Sao Paulo, Brazil, to assess the cervicovaginal levels of human beta
      defensin (hBD) 1, 2, 3, and 4 during Chlamydia trachomatis infection. PATIENTS
      AND METHODS: Cervicovaginal samples were collected for Pap testing and assessing
      the presence of infection by C. trachomatis, human papillomavirus, Neisseria
      gonorrhoeae, and Trichomonas vaginalis. Vaginal smears were taken to evaluate
      local microbiota. Human beta-defensin levels were determined using enzyme-linked
      immunosorbent assay in cervicovaginal fluid samples. Seventy-four women with
      normal vaginal microbiota and no evidence of infection were included in hBD
      quantification assays; 37 tested positive for C. trachomatis and 37 were
      negative. Statistical analysis was performed using Mann-Whitney U test. RESULTS:
      Women positive for C. trachomatis had significantly lower cervicovaginal hBD-1,
      hBD-2, and hBD-3 compared with those who tested negative (hBD-1: 0 pg/mL [0-2.1]
      vs 1.6 pg/mL [0-2.4], p < .0001; hBD-2: 0 pg/mL [0-3.9] vs 0.61 pg/mL [0-8.9], p
      = .0097; and hBD-3: 0 pg/mL [0-4.3] vs 0.28 pg/mL [0-8.4], p = .0076). Human beta
      defensin 4 was not detected. CONCLUSIONS: Lower levels of hBD-1, hBD-2, and hBD-3
      in cervicovaginal fluid were detected in the presence of C. trachomatis
      infection.

PMID- 28430680
TI  - Massive Cellular Angiofibroma of the Vulva.

PMID- 28430681
TI  - Dangerous Liaisons: Pelvic Variant of Lemierre Syndrome by Right Common Iliac
      Vein Thrombophlebitis After Sexual Intercourse.

PMID- 28430682
TI  - Attempted Development of a Tool to Predict Anesthesia Preparation Time From
      Patient-Related and Procedure-Related Characteristics.
AB  - BACKGROUND: Operating room (OR) utilization generally ranges from 50% to 75%.
      Inefficiencies can arise from various factors, including prolonged anesthesia
      preparation time, defined as the period from induction of anesthesia until
      patients are considered ready for surgery. Our goal was to use patient-related
      and procedure-related factors to develop a model predicting anesthesia
      preparation time. METHODS: From the electronic medical records of adults who had
      noncardiac surgery at the Cleveland Clinic Main Campus, we developed a model that
      used a dozen preoperative factors to predict anesthesia preparation time. The
      model was based on multivariable regression with "Least Absolute Shrinkage and
      Selection Operator" and 10-fold cross-validation. The overall performance of the
      final model was measured by R, which describes the proportion of the variance in
      anesthesia preparation time that is explained by the model. RESULTS: A total of
      43,941 cases met inclusion and exclusion criteria. Our final model had only
      moderate discriminative ability. The estimated adjusted R for prediction model
      was 0.34 for the training data set and 0.27 for the testing data set.
      CONCLUSIONS: Using preoperative factors, we could explain only about a quarter of
      the variance in anesthesia preparation time-an amount that is probably of limited
      clinical value.

PMID- 28430684
TI  - Flurbiprofen Axetil Provides Effective Analgesia Without Changing the Pregnancy
      Rate in Ultrasound-Guided Transvaginal Oocyte Retrieval: A Double-Blind
      Randomized Controlled Trial.
AB  - BACKGROUND: In this prospective double-blind randomized study, we evaluated the
      analgesic effect and potential effect on pregnancy rate of the nonsteroidal anti
      inflammatory drug flurbiprofen axetil in patients undergoing ultrasound-guided
      transvaginal oocyte retrieval under propofol-remifentanil anesthesia. METHODS: A
      total of 200 patients scheduled to undergo ultrasound-guided transvaginal oocyte
      retrieval were randomly allocated to receive 1.5 mg/kg of flurbiprofen axetil (FA
      group) or placebo (control group) 30 minutes before the procedure. Postoperative
      pain scores, embryo implantation rate, and pregnancy rate were recorded.
      Neuroendocrine biomarkers and prostaglandin E2 levels in follicular fluid were
      tested after oocyte retrieval. RESULTS: Patients in the FA group awakened earlier
      after surgery than patients in the control group (3.3 +/- 2.6 vs 5.3 +/- 3.4
      minutes, P < .05) and had lower pain scores than patients in the control group
      (2.0 [0.0, 2.8] vs 5.0 [3.0, 5.0], P< .001). The difference in pregnancy rates
      between the 2 groups (44%-44%) was 0% (conventional 2-sided 95% confidence
      interval, -13.8% to 13.8%). The lower limit of the 90% 1-sided confidence
      interval for this difference was -9.0%, which was within the predefined
      noninferiority margin of -15.0%. The concentration of prostaglandin E2 in
      follicular fluid was decreased in the FA group (24.51 +/- 1.52 vs 25.15 +/- 1.49
      pg/mL, P = .039), although the difference does not appear to be clinically
      important. CONCLUSIONS: Flurbiprofen axetil given before ultrasound-guided
      transvaginal oocyte retrieval for patients under propofol-remifentanil general
      anesthesia relieves pain without any detrimental effect on clinical pregnancy
      rate.

PMID- 28430686
TI  - In Response.

PMID- 28430687
TI  - Brain Tissue Oximetry: What Are We Really Measuring?

PMID- 28430688
TI  - Cricoid Pressure, Gender, and Black Cats.

PMID- 28430689
TI  - Perioperative Outcomes of Robotic-Assisted Hysterectomy Compared With Open
      Hysterectomy.
AB  - BACKGROUND: Increasing numbers of robotic hysterectomies (RH) are being
      performed. To provide ventilation (with pneumoperitoneum and steep Trendelenburg
      position) for these procedures, utilization of lung protective strategies with
      limiting airway pressures and tidal volumes is difficult. Little is known about
      the effects of intraoperative mechanical ventilation and high peak airway
      pressures on perioperative complications. We performed a retrospective review to
      determine whether patients undergoing RH had increased pulmonary complications
      compared to total abdominal hysterectomy (TAH). METHODS: We performed a single
      center retrospective review comparing the intraoperative, anesthetic, and
      immediate and 30-day postoperative course of patients undergoing RH to TAH,
      including intraoperative ventilatory parameters and respiratory complications.
      Patients undergoing TAH (201) from 2004 to 2006 were compared to RH (251) from
      2009 to 2012. It was our hypothesis that patients undergoing RH would have
      increased incidence of postoperative pulmonary complications. A secondary
      hypothesis was that morbid obesity predicts pulmonary complications in patients
      undergoing RH. Complications were compared between groups using Fisher's exact
      test. To account for potential confounders, the primary analysis was performed
      for a subgroup of patients matched on the propensity for RH. RESULTS: A total of
      351 RH and 201 TAH procedures are included. Higher inspiratory pressures were
      required in ventilation of the RH group (median [25th, 75th] 31 [26, 36] cm H2O)
      than the TAH group (23 [19, 27] cm H2O) (P < .001) at 30 minutes after incision.
      Peak inspiratory pressures at 30 minutes after incision for RH increased
      according to increasing body mass index group (P < .001). There were 163 RH and
      163 TAH procedures included in the propensity matched analysis. From this
      analysis, there were no significant differences in cardiopulmonary complications
      between RH and TAH (0.6% vs 1.2%; odds ratio = 2.0, 95% confidence interval = 0.2
      2.4; P = 1.00). Surgical site infection was significantly lower in the RH
      compared to TAH group (0.6% vs 8.6%; P < .001). Hospital length of stay was
      longer for those who underwent TAH versus RH (median [25th, 75th] 2 [2, 3] vs 1
      [0, 2] days; P < .001). CONCLUSIONS: There was no significant difference in
      perioperative complications in obese and morbidly obese women compared to
      nonobese undergoing RH. Patients undergoing RH had shorter hospital stays, fewer
      infectious complications, and no increase in overall complications compared to
      TAH. Higher ventilatory airway pressures (RH versus TAH and obese versus
      nonobese) did not result in an increase in cardiopulmonary or overall
      complications. We believe that peritoneal insufflation attenuates the effect of
      high airway pressures by raising intrapleural pressure and reducing the gradient
      across terminal bronchioles and alveoli. Thus, we propose that lung protective
      strategies for patients undergoing RH account for the markedly elevated
      intraperitoneal and intrapleural pressures, whereas transpulmonary airway
      pressures remain static. This reduced transpulmonary gradient attenuates the
      strain on lung tissue that would otherwise be imposed by ventilation at high
      pressures.

PMID- 28430690
TI  - Scale-Ampule Assembly to Assess Ramp Position for Airway Management.

PMID- 28430691
TI  - Continuous Peripheral Nerve Blocks and Alternative Regional Analgesic Modalities:
      Clarification Regarding Relative Superiority.

PMID- 28430692
TI  - Lack of Association Between the Use of Nerve Blockade and the Risk of
      Postoperative Chronic Opioid Use Among Patients Undergoing Total Knee
      Arthroplasty: Evidence From the Marketscan Database.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is associated with high rates of
      prolonged opioid use after surgery (10%-34%). By decreasing opioid use in the
      immediate postoperative period, perioperative nerve blockade has been
      hypothesized to decrease the risk of persistent opioid use. METHODS: Using health
      care utilization data, we constructed a sample of 120,080 patients undergoing TKA
      between 2002 and 2012 and used billing data to identify the utilization of
      peripheral or neuraxial blockade. We then used a multivariable logistic
      regression to estimate the association between nerve blockade and the risk of
      chronic opioid use, defined as having filled >=10 prescriptions or >=120 days'
      supply for an opioid in the first postsurgical year. Our analyses were adjusted
      for an extensive set of potential confounding variables, including medical
      comorbidities, previous opioid use, and previous use of other medications.
      RESULTS: We did not find an association between nerve blockade and the risk of
      postsurgical chronic opioid use across any of these 3 groups: adjusted relative
      risk (ARR) 0.984 for patients opioid-naive in the year before surgery (98.3%
      confidence interval [CI], 0.870-1.12, P = .794), ARR 1.02 for intermittent opioid
      users (98.3% CI, 0.948-1.09, P = .617), and ARR 0.986 (98.3% CI, 0.963-1.01, P =
      .257) for chronic opioid users. Similar results held for alternative measures of
      postsurgical opioid use. CONCLUSIONS: Although the use of perioperative nerve
      blockade for TKA may improve short-term outcomes, the analyzed types of blocks do
      not appear to decrease the risk of persistent opioid use in the longer term.

PMID- 28430693
TI  - In Response.

PMID- 28430695
TI  - Cerebral Recovery Index: Reliable Help for Prediction of Neurologic Outcome After
      Cardiac Arrest.
AB  - OBJECTIVE: Early electroencephalography measures contribute to outcome prediction
      of comatose patients after cardiac arrest. We present predictive values of a new
      cerebral recovery index, based on a combination of quantitative
      electroencephalography measures, extracted every hour, and combined by the use of
      a random forest classifier. DESIGN: Prospective observational cohort study.
      SETTING: Medical ICU of two large teaching hospitals in the Netherlands.
      PATIENTS: Two hundred eighty-three consecutive comatose patients after cardiac
      arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Continuous
      electroencephalography was recorded during the first 3 days. Outcome at 6 months
      was dichotomized as good (Cerebral Performance Category 1-2, no or moderate
      disability) or poor (Cerebral Performance Category 3-5, severe disability,
      comatose, or death). Nine quantitative electroencephalography measures were
      extracted. Patients were randomly divided over a training and validation set.
      Within the training set, a random forest classifier was fitted for each hour
      after cardiac arrest. Diagnostic accuracy was evaluated in the validation set.
      The relative contributions of resuscitation parameters and patient
      characteristics were evaluated. The cerebral recovery index ranges from 0
      (prediction of death) to 1 (prediction of full recovery). Poor outcome could be
      predicted at a threshold of 0.34 without false positives at a sensitivity of 56%
      at 12 hours after cardiac arrest. At 24 hours, sensitivity of 65% with a false
      positive rate of 6% was obtained. Good neurologic outcome could be predicted with
      sensitivities of 63% and 58% at a false positive rate of 6% and 7% at 12 and 24
      hours, respectively. Adding patient characteristics was of limited additional
      predictive value. CONCLUSIONS: A cerebral recovery index based on a combination
      of intermittently extracted, optimally combined quantitative
      electroencephalography measures provides unequalled prognostic value for comatose
      patients after cardiac arrest and enables bedside EEG interpretation of
      unexperienced readers.

PMID- 28430694
TI  - Iron Loading Exaggerates the Inflammatory Response to the Toll-like Receptor 4
      Ligand Lipopolysaccharide by Altering Mitochondrial Homeostasis.
AB  - BACKGROUND: Perioperative and critically ill patients are often exposed to iron
      (in the form of parenteral-iron administration or blood transfusion) and
      inflammatory stimuli, but the effects of iron loading on the inflammatory
      response are unclear. Recent data suggest that mitochondrial reactive oxygen
      species have an important role in the innate immune response and that increased
      mitochondrial reactive oxygen species production is a result of dysfunctional
      mitochondria. We tested the hypothesis that increased intracellular iron
      potentiates lipopolysaccharide-induced inflammation by increasing mitochondrial
      reactive oxygen species levels. METHODS: Murine macrophage cells were incubated
      with iron and then stimulated with lipopolysaccharide. C57BL/6 wild-type mice
      were intraperitoneally injected with iron and then with lipopolysaccharide.
      Markers of inflammation and mitochondrial superoxide production were examined.
      Mitochondrial homeostasis (the balance between mitochondrial biogenesis and
      destruction) was assessed, as were mitochondrial mass and the proportion of
      nonfunctional to total mitochondria. RESULTS: Iron loading of mice and cells
      potentiated the inflammatory response to lipopolysaccharide. Iron loading
      increased mitochondrial superoxide production. Treatment with MitoTEMPO, a
      mitochondria-specific antioxidant, blunted the proinflammatory effects of iron
      loading. Iron loading increased mitochondrial mass in cells treated with
      lipopolysaccharide and increased the proportion of nonfunctional mitochondria.
      Iron loading also altered mitochondrial homeostasis to favor increased production
      of mitochondria. CONCLUSIONS: Acute iron loading potentiates the inflammatory
      response to lipopolysaccharide, at least in part by disrupting mitochondrial
      homeostasis and increasing the production of mitochondrial superoxide. Improved
      understanding of iron homeostasis in the context of acute inflammation may yield
      innovative therapeutic approaches in perioperative and critically ill patients.

PMID- 28430696
TI  - Sequential Analysis of a Panel of Biomarkers and Pathologic Findings in a
      Resuscitated Rat Model of Sepsis and Recovery.
AB  - OBJECTIVES: To characterize the temporal pattern of a panel of blood and urinary
      biomarkers in an animal model of fecal peritonitis and recovery. DESIGN:
      Prospective observational animal study. SETTING: University research laboratory.
      SUBJECTS: Male Wistar rats. INTERVENTIONS: A fluid-resuscitated, long-term (3 d)
      rat model of sepsis (fecal peritonitis) and recovery was used to understand the
      temporal association of sepsis biomarkers in relation to systemic hemodynamics,
      inflammation, and renal function. At predefined time points (3, 6, 12, 24, 48, 72
      hr), animals (>= 6 per group) underwent echocardiography, blood and urine
      sampling, and had kidneys taken for histological analysis. Comparison was made
      against sham-operated controls and naive animals. MEASUREMENTS AND MAIN RESULTS:
      The systemic proinflammatory response was maximal at 6 hours, corresponding with
      the nadir of stroke volume. Serum creatinine peaked late (24 hr), when clinical
      recovery was imminent. Histological evidence of tubular injury and cell death was
      minimal. After a recovery period, all biomarkers returned to levels approaching
      those observed in sham animals. Apart from urine clusterin and interleukin-18,
      all other urinary biomarkers were elevated at earlier time points compared with
      serum creatinine. Urine neutrophil gelatinase-associated lipocalin was the most
      sensitive marker among those studied, rising from 3 hours. While serum creatinine
      fell at 12 hours, serum cystatin C increased, suggestive of decreased creatinine
      production. CONCLUSIONS: Novel information is reported on the temporal profile of
      a panel of renal biomarkers in sepsis in the context of systemic and renal
      inflammation and recovery. Insight into the pathophysiology of acute kidney
      injury is gleaned from the temporal change markers of renal injury (urine
      neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, calbindin),
      followed by a marker of cell cycle arrest (urine insulin-like growth factor
      binding protein 7) and, finally, by functional markers of filtration (serum
      creatinine and cystatin C). These clinically relevant findings should have
      significant influence on future clinical testing.

PMID- 28430698
TI  - The Right Ventricle Is Dilated During Resuscitation From Cardiac Arrest Caused by
      Hypovolemia: A Porcine Ultrasound Study.
AB  - OBJECTIVES: Dilation of the right ventricle during cardiac arrest and
      resuscitation may be inherent to cardiac arrest rather than being associated with
      certain causes of arrest such as pulmonary embolism. This study aimed to compare
      right ventricle diameter during resuscitation from cardiac arrest caused by
      hypovolemia, hyperkalemia, or primary arrhythmia (i.e., ventricular
      fibrillation). DESIGN: Thirty pigs were anesthetized and then randomized to
      cardiac arrest induced by three diffrent methods. Seven minutes of untreated
      arrest was followed by resuscitation. Cardiac ultrasonographic images were
      obtained during induction of cardiac arrest, untreated cardiac arrest, and
      resuscitation. The right ventricle diameter was measured. Primary endpoint was
      the right ventricular diameter at the third rhythm analysis. SETTING: University
      hospital animal laboratory. SUBJECTS: Female crossbred Landrace/Yorkshire/Duroc
      pigs (27-32 kg). INTERVENTIONS: Pigs were randomly assigned to cardiac arrest
      caused by either hypovolemia, hyperkalemia, or primary arrhythmia. MEASUREMENTS
      AND MAIN RESULTS: At the third rhythm analysis during resuscitation, the right
      ventricle diameter was 32 mm (95% CI, 29-35) in the hypovolemia group, 29 mm (95%
      CI, 26-32) in the hyperkalemia group, and 25 mm (95% CI, 22-28) in the primary
      arrhythmia group. This was larger than baseline for all groups (p = 0.03). When
      comparing groups at the third rhythm analysis, the right ventricle was larger for
      hypovolemia than for primary arrhythmia (p < 0.001). CONCLUSIONS: The right
      ventricle was dilated during resuscitation from cardiac arrest caused by
      hypovolemia, hyperkalemia, and primary arrhythmia. These findings indicate that
      right ventricle dilation may be inherent to cardiac arrest, rather than being
      associated with certain causes of arrest. This contradicts a widespread clinical
      assumption that in hypovolemic cardiac arrest, the ventricles are collapsed
      rather than dilated.

PMID- 28430699
TI  - Clinical experience and diagnostic algorithm of vulval Crohn's disease.
AB  - BACKGROUND AND AIM: Vulval Crohn's disease (VCD) is a rare extraintestinal
      cutaneous manifestation of Crohn's disease. No consensus on the diagnostic workup
      and therapeutic management of this condition has been provided in the current
      literature. PATIENTS AND METHODS: Retrospective, multicentre descriptive case
      series of female patients diagnosed and treated with VCD. By chart review, data
      on initial symptoms, clinical courses, histologic findings and therapeutic
      management were collected. RESULTS: Fifteen female patients with a median age of
      28 years (interquartile range: 28-44 years) suffering from Crohn's disease of the
      ileum (27%), colon (33%) and ileocolon (40%) were included. VCD manifested most
      frequently with vulval swelling (93%), pain (80%) and erythema (73%). Histologic
      analysis demonstrated granulomatous inflammation in 78% and a mixed inflammatory
      cell infiltrate in 67% of cases. In eight (53%) cases, topical therapy resulted
      in temporary reduction of vulval symptoms. Combotreatment with immunosuppressive
      agents and tumour necrosis factor alpha inhibitors was the most effective second
      line therapy: five (33%) patients achieved sustained clinical remission with this
      therapeutic strategy. CONCLUSION: The diagnostic workup of VCD is challenging and
      should be approached in a multidisciplinary manner. Histopathologic analysis of
      the vulva supports the diagnosis. Topical therapy and systemic treatment with
      immunosuppressive agents and tumour necrosis factor alpha inhibitors are advised
      to treat this condition.

PMID- 28430697
TI  - Abusive Head Trauma and Mortality-An Analysis From an International Comparative
      Effectiveness Study of Children With Severe Traumatic Brain Injury.
AB  - OBJECTIVES: Small series have suggested that outcomes after abusive head trauma
      are less favorable than after other injury mechanisms. We sought to determine the
      impact of abusive head trauma on mortality and identify factors that
      differentiate children with abusive head trauma from those with traumatic brain
      injury from other mechanisms. DESIGN: First 200 subjects from the Approaches and
      Decisions in Acute Pediatric Traumatic Brain Injury Trial-a comparative
      effectiveness study using an observational, cohort study design. SETTING: PICUs
      in tertiary children's hospitals in United States and abroad. PATIENTS:
      Consecutive children (age < 18 yr) with severe traumatic brain injury (Glasgow
      Coma Scale <= 8; intracranial pressure monitoring). INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Demographics, injury-related scores, prehospital,
      and resuscitation events were analyzed. Children were dichotomized based on
      likelihood of abusive head trauma. A total of 190 children were included (n = 35
      with abusive head trauma). Abusive head trauma subjects were younger (1.87 +/-
      0.32 vs 9.23 +/- 0.39 yr; p < 0.001) and a greater proportion were female (54.3%
      vs 34.8%; p = 0.032). Abusive head trauma were more likely to 1) be transported
      from home (60.0% vs 33.5%; p < 0.001), 2) have apnea (34.3% vs 12.3%; p = 0.002),
      and 3) have seizures (28.6% vs 7.7%; p < 0.001) during prehospital care. Abusive
      head trauma had a higher prevalence of seizures during resuscitation (31.4 vs
      9.7%; p = 0.002). After adjusting for covariates, there was no difference in
      mortality (abusive head trauma, 25.7% vs nonabusive head trauma, 18.7%; hazard
      ratio, 1.758; p = 0.60). A similar proportion died due to refractory intracranial
      hypertension in each group (abusive head trauma, 66.7% vs nonabusive head trauma,
      69.0%). CONCLUSIONS: In this large, multicenter series, children with abusive
      head trauma had differences in prehospital and in-hospital secondary injuries
      which could have therapeutic implications. Unlike other traumatic brain injury
      populations in children, female predominance was seen in abusive head trauma in
      our cohort. Similar mortality rates and refractory intracranial pressure deaths
      suggest that children with severe abusive head trauma may benefit from therapies
      including invasive monitoring and adherence to evidence-based guidelines.

PMID- 28430700
TI  - Prescriber Compliance With Liver Monitoring Guidelines for Pazopanib in the
      Postapproval Setting: Results From a Distributed Research Network.
AB  - OBJECTIVES: Pazopanib received US Food and Drug Administration approval in 2009
      for advanced renal cell carcinoma. During clinical development, liver chemistry
      abnormalities and adverse hepatic events were observed, leading to a boxed
      warning for hepatotoxicity and detailed label prescriber guidelines for liver
      monitoring. As part of postapproval regulatory commitments, a cohort study was
      conducted to assess prescriber compliance with liver monitoring guidelines.
      METHODS: Over a 4-year period, a distributed network approach was used across 3
      databases: US Veterans Affairs Healthcare System, a US outpatient oncology
      community practice database, and the Dutch PHARMO Database Network. Measures of
      prescriber compliance were designed using the original pazopanib label guidelines
      for liver monitoring. RESULTS: Results from the VA (n = 288) and oncology
      databases (n = 283) indicate that prescriber liver chemistry monitoring was less
      than 100%: 73% to 74% compliance with baseline testing and 37% to 39% compliance
      with testing every 4 weeks. Compliance was highest near drug initiation and
      decreased over time. Among patients who should have had weekly testing, the
      compliance was 56% in both databases. The more serious elevations examined,
      including combinations of liver enzyme elevations meeting the laboratory
      definition of Hy's law were infrequent but always led to appropriate
      discontinuation of pazopanib. Only 4 patients were identified for analysis in the
      Dutch database; none had recorded baseline testing. CONCLUSIONS: In this
      population-based study, prescriber compliance was reasonable near pazopanib
      initiation but low during subsequent weeks of treatment. This study provides
      information from real-world community practice settings and offers feedback to
      regulators on the effectiveness of label monitoring guidelines.This is an open
      access article distributed under the terms of the Creative Commons Attribution
      Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible
      to download and share the work provided it is properly cited. The work cannot be
      changed in any way or used commercially without permission from the journal.

PMID- 28430701
TI  - Tear Function and Ocular Surface Alterations After Accelerated Corneal Collagen
      Crosslinking in Progressive Keratoconus.

PMID- 28430702
TI  - RE: Tear Function and Ocular Surface Alterations After Accelerated Corneal
      Collagen Crosslinking in Progressive Keratoconus.

PMID- 28430703
TI  - Evidence-based Recommendations for Pediatric Orthopaedic Practice.
AB  - BACKGROUND: Evidence-based medicine has become the cornerstone to guide clinical
      practice decision-making. Evidence-based medicine integrates the strongest
      available evidence with clinical expertise to make decisions about clinical care.
      The quality of the evidence depends upon the soundness of the study methodology
      to allow for meaningful interpretation of the clinical results. The purpose of
      this review is to analyze the methodological design and clinical findings of
      published pediatric orthopaedic studies to determine their ability to change or
      influence clinical practice. METHODS: This is the first in a series of evidence
      based reviews in pediatric orthopaedics. The pediatric orthopaedic literature was
      reviewed for randomized controlled trials (RCTs) published in 2013 to 2014. Two
      RCTs were selected from the Journal of Bone and Joint Surgery for in depth
      methodological review and analysis. Methodological reviews were performed by 2
      orthopaedic surgeons with advanced research degrees. Following this, 2 clinical
      experts reviewed the articles to rate the clinical impact or value of each study.
      Methodological and clinical reviews were compiled, and a final recommendation on
      impact to change clinical practice was made based on both review components at
      the consensus of the panel. RESULTS: The first study reviewed investigated the
      impact of physical therapy on function following supracondylar humeral fractures
      in children. The reviewers deemed the superiority study to of sound design, and
      conclusions appropriate for the methodology used and clinical findings. The
      results do not compel a recommendation to change clinical practice. The second
      study investigated the impact of Botulinum Toxin A with casting for the treatment
      of idiopathic toe-walking in children. Although of relatively sound design, the
      sample size was too small to appropriately perform some statistical comparisons.
      No recommendation to change clinical practice could be made. CONCLUSION: Both
      RCTs reviewed were superiority studies with a negative result. No recommendation
      to change clinical practice could be made. SIGNIFICANCE: Interpretation of
      superiority studies with nonsignificant findings must be done with caution. The
      findings of both of these RCTs highlight the need for more noninferiority trials
      in the pediatric orthopaedic literature in order to appropriately demonstrate no
      difference between 2 treatment options.

PMID- 28430704
TI  - Functional effects of treadmill-based gait training at faster speeds in stroke
      survivors: a prospective, single-group study.
AB  - To examine the functional effects of walking retraining at faster than self
      selected speed (SSS). Ten individuals with chronic stroke participated in a 4
      week training over a treadmill at walking speeds 40% faster than SSS, three times
      per week, 30 min/session. Outcome measures assessed before, after, and 2 months
      after the end of intervention were the Timed Up and Go, the 6-Minute Walk, the 10
      Meter Walk test, the Modified Ashworth Scale, SSS, and fastest comfortable speed.
      After 4 weeks of training, all outcome measures showed clinically meaningful and
      statistically significant improvements (P<0.05) that were maintained at 2 months
      after the end of the training. The results showed that a strategy of training at
      a speed 40% faster than SSS can improve functional activity in individuals with
      chronic stroke, with effects lasting up to 2 months after the intervention.

PMID- 28430705
TI  - Disparities in Female Breast Cancer Stage at Diagnosis in New Jersey: A Spatial
      Temporal Analysis.
AB  - BACKGROUND: Despite improvements in early detection of breast cancer, disparities
      persist in stage at diagnosis, which is an important prognostic factor. METHODS:
      We used the space-time scan statistic in SaTScan to identify geographic areas and
      time periods with significantly elevated proportions of female breast cancer
      diagnosed at the in situ or distant stage in New Jersey. The analyses were
      conducted with census tracts as the geographic unit of analysis, elliptical
      spatial windows, 3-year temporal windows, and Poisson models. Statistical
      significance was determined by 999 Monte Carlo simulations (P < .05); significant
      clusters were mapped in ArcMap. Breast cancer cases within the clusters were
      compared with breast cancer cases outside the clusters on demographic,
      socioeconomic, and clinical factors using the Pearson chi-square test (P < .05).
      In addition, populations within the clusters were compared with the population
      outside the clusters on demographic and socioeconomic factors. RESULTS: After
      exclusions, 126 756 cases of primary female breast cancer diagnosed in 1997 to
      2011 from the New Jersey State Cancer Registry were included in the analysis. One
      distant stage breast cancer cluster was identified in northeastern New Jersey
      from 1997 through 2011 (n = 26 244, relative risk [RR] = 1.42, P < .001). Two in
      situ breast cancer clusters were found in northeastern New Jersey from 2004
      through 2011 (n = 12 496, RR = 1.35, P < .001) and in central New Jersey from
      2006 through 2011 (n = 29 319, RR = 1.24, P < .001). The distant stage cluster
      contained relatively high percentages of minority and lower socioeconomic status
      (SES) breast cancer cases and populations, whereas the in situ clusters had
      relatively low percentages of minority and lower SES breast cancer cases and
      populations. CONCLUSION: Although there have been improvements since an earlier
      study of distant stage breast cancer diagnosed in 1995 to 1997, disparities in
      stage at diagnosis continue. These findings can be used by our local cancer
      control partners to target specific populations for interventions such as breast
      cancer education and mammography screening, as well as by state legislative and
      public health authorities for resource allocation.

PMID- 28430706
TI  - Rare Pleurostomophora richardsiae Mass Causing Transient Nasolacrimal Duct
      Obstruction.
AB  - Transient nasolacrimal duct obstruction secondary to a mass lesion compressing
      the sac or sac-duct junction is rare. The authors report a case of a young female
      who presented to the authors with complaints of watering and a mass lesion in the
      lacrimal sac region. An organized perilacrimal mass filled with thick pultaceous
      material was noted during surgery. Following the drainage of the mass lesion,
      irrigation of the lacrimal system was freely patent. Microbiological examination
      and DNA sequencing targeting interspacer region was suggestive of
      Pleurostomophora richardsiae species. To the best of the authors' knowledge, this
      is only the second case report of a subcutaneous perilacrimal mass causing
      transient nasolacrimal duct obstruction by Pleurostomophora richardsiae.

PMID- 28430707
TI  - Subepidermal Calcinosis in the Ocular Adnexa: A Systematic Review.
AB  - PURPOSE: To review the clinical and histopathologic findings associated with
      subepidermal calcinosis of the eyelids. METHODS: A systematic review of the
      literature on subepidermal calcinosis of the eyelids was performed. Cases
      included were idiopathic in nature and met the histologic criteria for
      subepidermal calcinosis with calcium deposits in the dermis of the skin. RESULTS:
      Twenty-one publications presenting 53 cases of subepidermal calcinosis involving
      the eyelids were published between 1970 and 2016. Males were affected more than
      females (67% vs. 33%), and 89% of patients were 21 years of age or younger. A
      total of 63% were non-Caucasian. Most cases involved a single lesion (82%), and
      lesions were most frequently located on the upper eyelid (63%). In 81% of cases,
      the lesion was less than 5 mm in diameter. When reported, the treatment of choice
      was complete surgical excision. CONCLUSIONS: Subepidermal calcinosis should be
      considered in the differential diagnosis of idiopathic lesions on the eyelid,
      particularly in young males with no history of systemic disease or laboratory
      abnormalities. These nodules usually present as painless, small, firm, mobile
      solitary cutaneous lesions with a predilection for the upper eyelid. Diagnosis is
      confirmed by histopathology, and treatment is with surgical excision.

PMID- 28430708
TI  - The somatosensory-evoked potential in reaction time is gated and elicited earlier
      when the motor response to a somatosensory cue is faster.
AB  - The aim of this study was to investigate whether the somatosensory-evoked
      potential (SEP) is gated and elicited earlier when a motor response to a
      somatosensory stimulus is faster. In healthy humans, the left index finger and
      thumb were pinched in response to a somatosensory stimulus administered over the
      left median nerve. The SEP elicited by this stimulus when producing a fast motor
      response was compared with that when producing a slow motor response. The
      amplitudes of N18 and frontal P40 when producing a fast motor response were
      smaller than those when producing a slow motor response. The latencies of frontal
      P22 and P40 when producing a fast motor response were shorter than those when
      producing a slow motor response. These findings indicated that the responses of
      the primary sensory and frontal areas elicited by a somatosensory stimulus are
      gated and that the responses of the frontal areas elicited by this stimulus occur
      earlier when a motor response to this stimulus is faster. The enhanced efficiency
      or increased speed of the stimulus identification process may be related to the
      gating and early onset of the SEP components when producing a fast motor
      response.

PMID- 28430710
TI  - Angiotensin-converting enzyme insertion/deletion gene polymorphism and interferon
      beta treatment response in multiple sclerosis patients: a preliminary report.
AB  - We investigated the effect of the functional insertion/deletion (I/D)
      polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to
      interferon-beta (IFN-beta) therapy in Croatian and Slovenian patients with
      multiple sclerosis (MS). A total of 275 IFN-beta treated MS patients [162
      responders (Rs) and 113 nonresponders (NRs)] were genotyped by PCR. The ACE I/D
      genotype distribution and allele frequencies did not differ between female Rs and
      NRs. However, male NRs tended to have a greater prevalence of the DD genotype
      (P=0.073; odds ratio: 2.64; 95% confidence interval: 0.91-7.60) and a
      significantly higher frequency of the D allele (P=0.022; odds ratio: 2.43; 95%
      confidence interval: 1.13-5.20) than male Rs. Multiple forward stepwise
      regression analysis indicated that the negative response to IFN-beta therapy was
      associated with the ACE-DD genotype in men (beta=0.371; multiple R change: 0.132;
      P=0.009) and a higher pretreatment relapse rate in both men (beta=-0.438;
      multiple R change: 0.135; P=0.015) and women (beta=-0.208; multiple R change:
      0.042; P=0.034). The ACE I/D polymorphism and pretreatment relapse rate accounted
      for ~26.7% of the IFN-beta response variability among the men in the sample.
      Further studies of a larger number of MS patients from different populations are
      necessary to evaluate these preliminary findings.

PMID- 28430709
TI  - Vitamin D3 repressed astrocyte activation following lipopolysaccharide
      stimulation in vitro and in neonatal rats.
AB  - Vitamin D3 has been reported to be an immunity modulator and high levels of
      vitamin D3 are correlated with a decreased risk for developing diseases in the
      central nervous system. Astrocytes are important immune cells and contribute
      toward inflammation during neurological diseases. The vitamin D receptor has been
      reported to be expressed in astrocytes; however, the effect of vitamin D3 on
      astrocyte activation has not been studied. Here, we found that lipopolysaccharide
      stimulation in astrocytes could enhance the expression of vitamin D receptor and
      Cyp27B1, which encodes the enzyme for converting vitamin D3 into its active form.
      Vitamin D3 suppressed the expression of proinflammatory cytokines tumour necrosis
      factor-alpha, interleukin-1beta, vascular endothelial growth factor, and also
      TLR4 in activated astrocytes. Astrocyte activation was further found to be
      suppressed after the administration of vitamin D3 in neonatal rats injected with
      lipopolysaccharide in vivo. We demonstrated the antiactivation effect of vitamin
      D3 in astrocytes after lipopolysaccharide stimulation. Considering the function
      of reactive astrocytes in augmenting inflammatory response in neurodegeneration
      and brain injury, the finding that vitamin D3 administration may inhibit
      astrocyte activation may be potentially useful for the treatment of central
      nervous system disorders.

PMID- 28430711
TI  - Evaluation of KDR rs34231037 as a predictor of sunitinib efficacy in patients
      with metastatic renal cell carcinoma.
AB  - The identification of biomarkers able to predict clinical benefit from vascular
      endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors is urgently
      needed. Recently, Maitland and colleagues described an association between KDR
      rs34231037 and soluble VEGFR2 levels as well as pazopanib pharmacodynamics. We
      investigated in a well-characterized series of metastatic clear cell renal cell
      carcinoma patients whether rs34231037 could influence sunitinib response.
      Clinical data and DNA were available from an international series of 276
      patients. KDR-rs34231037 association with sunitinib response, clinical benefit,
      and progression-free survival was analyzed using logistic and Cox regression
      analyses. We found that G-allele carriers were over-represented among patients
      with clinical benefit during sunitinib treatment compared with those refractory
      to the treatment (odds ratio: 3.78; 95% confidence interval: 1.02-14.06; P=0.047,
      multivariable analysis). In conclusion, rs34231037 variant carriers seemed to
      have better sunitinib response than wild-type patients. Moreover, the association
      with tumor size reduction suggests that this single nucleotide polymorphism might
      also identify patients with successful tumor downsizing under anti-VEGFR therapy.

PMID- 28430712
TI  - Apolipoprotein E variants and genetic susceptibility to combat-related post
      traumatic stress disorder: a meta-analysis.
AB  - BACKGROUND: Apolipoprotein E (APOE) has recently been studied as a risk factor
      for association with developing combat-related post-traumatic stress disorder
      (PTSD) in the military population. These studies have yielded inconsistent
      findings. The present study carried out a meta-analysis to establish whether the
      APOE polymorphism confers increased susceptibility to combat-related PTSD.
      METHODS: PubMed, Medline, Embase, PsycInfo, and Google Scholar were searched for
      potential publications relating to patients with PTSD in military settings with
      combat exposure. Studies provided proper PTSD screening and genotype data on APOE
      gene variants were all considered for selection in the review. A random-effect
      model was used to calculate the pooled effect size (Cohen's d) and summary
      statistics. Sensitivity analyses and meta-regression were used to assess the
      between-study heterogeneity. Egger's test and rank-correlation test were also
      carried out to evaluate any potential publication bias. RESULTS: Our study showed
      a significant association between the APOE e4 gene variant and increased risk for
      developing combat-related PTSD, with an overall effect size of d equal to 0.28
      (95% confidence interval: 0.10-0.45) for e4 carriers versus noncarriers. In
      contrast, no statistically significant association was found for the APOE e2
      variant (d=0.59; 95% confidence interval: -0.29-1.47). CONCLUSION: The current
      meta-analysis provides corroborating evidence that supports the fact that the
      presence of the APOE e4 polymorphism confers greater susceptibility to combat
      related PTSD. Future studies with a larger sample size and better consistency in
      reporting standards are warranted to further evaluate these associations.

PMID- 28430713
TI  - A National Survey of Neonatologists: Barriers and Prerequisites to Introduce
      Point-of-Care Ultrasound in Neonatal ICUs.
AB  - Point-of-care (POC) ultrasound refers to the use of portable imaging. Although
      POC ultrasound is widely available to the neonatologists in Australia and Europe,
      neonatologists in the United States report limited availability. Our objective
      was to seek the US neonatologists' perception of barriers and prerequisites in
      adopting POC ultrasound in neonatal intensive care units. An online survey link
      was sent via e-mail to 3000 neonatologists included in the database maintained by
      the American Academy of Pediatrics. Survey results (n = 574) were reported as
      percentage of total responses. Personal experience requiring an urgent sonography
      in managing cardiac tamponade or pleural effusion was reported by 78%
      respondents. However, emergent ultrasound (<=10 min) was not available in 80% of
      the neonatal intensive care units. We compared the responses based on years of
      clinical experience (>20 vs <20 years), with 272 (48%) neonatologist reporting
      more than 20 years of experience. Similarly, results from neonatal fellowship
      programs were compared with nonteaching/teaching hospitals, with 288 (50%)
      replies from neonatology fellowship programs. Compared with senior
      neonatologists, respondents with less than 20 years of clinical experience
      consider POC ultrasound enhances safety and accuracy of clinical procedures (87%
      vs 82%) and favor adopting POC ultrasound in clinical practice (92% vs 84%).
      There were no differences in opinion from neonatology fellowship programs
      compared with the nonteaching/teaching hospitals. Lack of training guidelines,
      inadequate support from local radiology department, and legal concerns were
      reported as the top 3 primary barriers in adopting POC ultrasound. If these
      barriers could be resolved, 89% respondents were inclined to adopt POC ultrasound
      in clinical practice.

PMID- 28430714
TI  - Ultrasound Molecular Imaging of Inflammation in Mouse Abdominal Aorta.
AB  - OBJECTIVES: The aim of this study was to demonstrate a new clinically
      translatable ultrasound molecular imaging approach, modulated acoustic radiation
      force-based imaging, which is capable of rapid and reliable detection of
      inflammation as validated in mouse abdominal aorta. MATERIALS AND METHODS: Animal
      studies were approved by the Institutional Animal Care and Use Committee at the
      University of Virginia. C57BL/6 mice stimulated with tumor necrosis factor alpha,
      or fed with a high-fat diet, were used as inflammation (MInflammation) and diet
      induced obesity (DIO) (MDIO) models, respectively. C57BL/6 mice, not exposed to
      tumor necrosis factor alpha or DIO, were used as controls (MNormal). P-selectin
      targeted (MBP-selectin), vascular cell adhesion molecule (VCAM)-1-targeted
      (MBVCAM-1), and isotype control (MBControl) microbubbles were synthesized by
      conjugating anti-P-selectin, anti-VCAM-1, and isotype control antibodies to
      microbubbles, respectively. The abdominal aortas were imaged for 180 seconds
      during a constant infusion of microbubbles. A parameter, residual-to-saturation
      ratio (RSR), was used to assess P-selectin and VCAM-1. Statistical analysis was
      performed with the Student t test. RESULTS: For the inflammation model, RSR of
      the MInflammation + MBP-selectin group was significantly higher (40.9%, P <
      0.0005) than other groups. For the DIO model, RSR of the MDIO + MBVCAM-1 group
      was significantly higher (60.0%, P < 0.0005) than other groups.
      Immunohistochemistry staining of the abdominal aorta confirmed the expression of
      P-selectin and VCAM-1. CONCLUSIONS: A statistically significant assessment of P
      selectin and VCAM-1 in mouse abdominal aorta was achieved. This technique yields
      progress toward rapid targeted molecular imaging in large blood vessels and thus
      has the potential for early diagnosis, treatment selection, and risk
      stratification of atherosclerosis.

PMID- 28430715
TI  - Computed Tomography of the Head and Neck Region for Tumor Staging-Comparison of
      Dual-Source, Dual-Energy and Low-Kilovolt, Single-Energy Acquisitions.
AB  - PURPOSE: The aim of this study was to intra-individually compare the image
      quality obtained by dual-source, dual-energy (DSDE) computed tomography (CT)
      examinations and different virtual monoenergetic reconstructions to a low single
      energy (SE) scan. MATERIALS AND METHODS: Third-generation DSDE-CT was performed
      in 49 patients with histologically proven malignant disease of the head and neck
      region. Weighted average images (WAIs) and virtual monoenergetic images (VMIs)
      for low (40 and 60 keV) and high (120 and 190 keV) energies were reconstructed. A
      second scan aligned to the jaw, covering the oral cavity, was performed for every
      patient to reduce artifacts caused by dental hardware using a SE-CT protocol with
      70-kV tube voltages and matching radiation dose settings. Objective image quality
      was evaluated by calculating contrast-to-noise ratios. Subjective image quality
      was evaluated by experienced radiologists. RESULTS: Highest contrast-to-noise
      ratios for vessel and tumor attenuation were obtained in 40-keV VMI (all P <
      0.05). Comparable objective results were found in 60-keV VMI, WAI, and the 70-kV
      SE examinations. Overall subjective image quality was also highest for 40-keV,
      but differences to 60-keV VMI, WAI, and 70-kV SE were nonsignificant (all P >
      0.05). High kiloelectron volt VMIs reduce metal artifacts with only limited
      diagnostic impact because of insufficiency in case of severe dental hardware.
      CTDIvol did not differ significantly between both examination protocols (DSDE:
      18.6 mGy; 70-kV SE: 19.4 mGy; P = 0.10). CONCLUSIONS: High overall image quality
      for tumor delineation in head and neck imaging were obtained with 40-keV VMI.
      However, 70-kV SE examinations are an alternative and modified projections
      aligned to the jaw are recommended in case of severe artifacts caused by dental
      hardware.

PMID- 28430716
TI  - Simultaneous Multislice Accelerated Turbo Spin Echo Magnetic Resonance Imaging:
      Comparison and Combination With In-Plane Parallel Imaging Acceleration for High
      Resolution Magnetic Resonance Imaging of the Knee.
AB  - PURPOSE: We prospectively quantified the signal-to-noise ratio (SNR) and contrast
      to-noise ratio (CNR) of integrated parallel acquisition technique (PAT) and
      simultaneous multislice (SMS) acceleration and various combinations thereof, and
      we further compared two 4-fold-accelerated (PAT2-SMS2) high-resolution turbo spin
      echo (TSE) magnetic resonance imaging (MRI) protocols of the knee against a
      clinical 2-fold-accelerated (PAT2-SMS1) TSE standard. MATERIALS AND METHODS:
      Institutional review board approval was obtained, and all subjects gave informed
      consent. Fourteen knee MRI examinations were obtained (8 men, 6 women; mean age,
      46 years; age range, 28-62 years) using a 3 T MRI system and a TSE pulse sequence
      prototype that allowed for the combination of PAT and SMS acceleration. Predicted
      whole-body specific absorption rates were recorded for all pulse sequences. For
      quantitative analysis, the difference method was used to calculate SNR and CNR
      analysis of 6 different TSE acceleration schemes (PAT2-SMS1, PAT3-SMS1, PAT1
      SMS2, PAT1-SMS3, PAT2-SMS2, and PAT2-SMS3). For qualitative analysis, sagittal
      intermediate-weighted and axial fat-suppressed T2-weighted MR images were
      obtained with PAT2-SMS1 and PAT2-SMS2 acceleration schemes using similar
      parameters. One faster PAT2-SMS2 acceleration scheme with decreased repetition
      time and longer echo train was labeled with the addition SPEED for the purpose of
      this report. Two readers rated the data sets for image quality, structural
      visibility, and overall observer satisfaction using equidistant 5-point Likert
      scales. Readers additionally noted the presence of cartilage defects, meniscal
      tears, tendons and ligament tears, and bone marrow edema pattern. Friedman and
      Kruskal-Wallis tests were used. P values of less than 0.01 were considered
      significant. RESULTS: All pulse sequences were successfully executed and
      reconstructed inline. Whole-body specific absorption rates ranged between 1.4 and
      3.9 W/kg for all acquisitions and remained within mandated limits.
      Quantitatively, mean SNR and CNR were significantly higher for SMS than those for
      PAT and similar for PAT2-SMS2 and PAT2-SMS1. Fluid was brightest on PAT2-SMS1,
      whereas noise, edge sharpness, contrast resolution, and fat suppression were
      similar on PAT2-SMS1 and SMS2-PAT2 and mildly inferior on PAT2-SMS2 SPEED.
      Articular cartilage received mildly higher ratings on PAT2-SMS1, whereas
      visibility of menisci was mildly inferior on PAT2-SMS2 SPEED. Observer
      preferences were similarly high for PAT2-SMS1 and PAT2-SMS2 and mildly inferior
      for the faster PAT2-SMS2 SPEED images. Four cartilage defects and 2 meniscal
      tears were seen by both readers on all sequences. CONCLUSIONS: We demonstrate the
      signal preservation capabilities of SMS over PAT acceleration, which allow for
      similar SNR and CNR of 4-fold PAT2-SMS2 and 2-fold PAT2-SMS1 acceleration. Four
      fold-accelerated TSE through the combination of PAT2 and SMS2 enables
      approximately 50% shorter acquisition times compared with regular PAT2
      acceleration, similar quantitative and qualitative image quality, and holds
      promise for a meaningful increase of the efficiency of clinical 2-dimensional MRI
      of the knee.

PMID- 28430717
TI  - Multilateral Functional Alterations of Human Neutrophils in Sepsis: From the
      Point of Diagnosis to the Seventh Day.
AB  - Neutrophil functional changes caused by sepsis itself and their time-course
      variation have not been fully elucidated because previous studies targeted
      patients who had received therapeutic interventions. We explored the multilateral
      functions of circulating neutrophils in patients with severe sepsis or septic
      shock who had not yet undergone interventions, and followed their changes.
      Patients were treated based on the Surviving Sepsis Campaign Guidelines 2012.
      Neutrophil functions were evaluated on days 0 (before therapeutic intervention),
      3, and 7 in 59 septic patients. The clinical severity score (APACHE II and SOFA)
      and serum pro-/anti-inflammatory cytokine concentrations of the patients were
      significantly increased on day 0 and normalized on day 3. However, neutrophil
      priming state, estimated by measuring the fMLP-stimulated reactive oxygen
      species, was significantly elevated on day 0, further augmented on day 3, and
      then returned to day 0 levels on day 7 despite general resolution of the
      inflammatory response. The expression of CXC chemokine receptor 2 and paired
      immunoglobulin-like receptor alpha, assessed as surrogate markers of
      transmigration and adhesion potency, was suppressed most strongly on day 0 and
      gradually recovered. To conclude, contrary to the patient's clinical course,
      neutrophil priming state was augmented most strongly at 3 days after diagnosis of
      sepsis. Impaired transmigration and excessive adhesion potency were observed most
      prominently at diagnosis. These observations would partially explain the
      mechanism of development of multiple organ dysfunction of the host who is
      subjected to a secondary insult, and may provide an important perspective for the
      implementation of additional immune-modulating therapy in sepsis.

PMID- 28430719
TI  - Intertrochanteric Osteotomy for Femoral Neck Nonunion: Does "Undercorrection"
      Result in an Acceptable Rate of Femoral Neck Union?
AB  - OBJECTIVES: To analyze the radiographic outcomes of intertrochanteric osteotomy
      for the treatment of femoral neck nonunion with "undercorrection" of the Pauwels
      angle and relative preservation of the proximal femoral anatomy. DESIGN:
      Retrospective cohort study. SETTING: Level-1 trauma center. PATIENTS: Thirty-two
      patients with established femoral neck nonunions that had been treated with
      intertrochanteric osteotomy were retrospectively identified through Current
      Procedural Terminology codes. Seven patients were treated with 30 degree closing
      wedge osteotomy and 25 with a 20 degree or smaller osteotomy. INTERVENTION:
      Valgus-producing intertrochanteric osteotomy with a blade plate. MAIN OUTCOME
      MEASUREMENTS: Femoral neck and intertrochanteric osteotomy osseous union.
      RESULTS: Thirty-one of 32 patients (97%) went on to osseous union of the femoral
      neck and all intertrochanteric osteotomies healed. There was no significant
      difference in the rate of union of the femoral neck between those patients
      treated with 30 versus 20 degree or less osteotomies. After osteotomy, the mean
      Pauwels angle decreased from 71 degrees (range 52-95 degrees) to 47 degrees
      (range 23-67 degrees) and the mean proximal femoral offset decreased by 11 mm
      (range 0-23 mm). Seven patients developed radiographic signs of avascular
      necrosis after osteotomy (22%). Three patients of these patients were converted
      to total hip arthroplasty (9%). Patients treated with a 30 degree osteotomy were
      more likely to develop avascular necrosis (67% vs. 12%, P-value = 0.014).
      CONCLUSIONS: Valgus-producing intertrochanteric osteotomy with a smaller degree
      of correction than has been traditionally described leads to an excellent rate of
      radiographic union while preserving more of the native proximal femoral anatomy.
      LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 28430720
TI  - The Effect of Insertion Technique on Temperatures for Standard and Self-Drilling
      External Fixation Pins.
AB  - OBJECTIVES: No studies have assessed the effects of parameters associated with
      insertion temperature in modern self-drilling external fixation pins. The current
      study assessed how varying the presence of irrigation, insertion speed, and force
      impacted the insertion temperatures of 2 types of standard and self-drilling
      external fixation half pins. METHODS: Seventy tests were conducted with 10 trials
      for 4 conditions on self-drilling pins, and 3 conditions for standard pins. Each
      test used a thermocouple inside the pin to measure temperature rise during
      insertion. RESULTS: Adding irrigation to the standard pin insertion significantly
      lowered the maximum temperature (P <0.001). Lowering the applied force for the
      standard pin did not have a significant change in temperature rise. Applying
      irrigation during the self-drilling pin tests dropped average rise in temperature
      from 151.3 +/- 21.6 degrees C to 124.1 +/- 15.3 degrees C (P = 0.005). When the
      self-drilling pin insertion was decreased considerably from 360 to 60 rpm, the
      temperature decreased significantly from 151.3 +/- 21.6 degrees C to 109.6 +/-
      14.0 degrees C (P <0.001). When the force applied increased significantly, the
      corresponding self-drilling pin temperature increase was not significant.
      CONCLUSIONS: The standard pin had lower peak temperatures than the self-drilling
      pin for all conditions. Moreover, slowing down the insertion speed and adding
      irrigation helped mitigate the temperature increase of both pin types during
      insertion.

PMID- 28430718
TI  - Trauma Collaborative Care Intervention: Effect on Surgeon Confidence in Managing
      Psychosocial Complications After Orthopaedic Trauma.
AB  - OBJECTIVES: The impact of the Trauma Collaborative Care (TCC) program on surgeon
      confidence in managing the psychosocial sequelae of orthopaedic trauma was
      evaluated as part of a larger prospective, multisite, cluster clinical trial. We
      compared confidence and perceived resource availability among surgeons practicing
      in trauma centers that implemented the TCC program with orthopaedic trauma
      surgeons in similar trauma centers that did not implement the TCC. DESIGN:
      Prospective cohort design. SETTING: Level-I trauma centers. PARTICIPANTS:
      Attending surgeons and fellows (N = 95 Pre and N = 82 Post). MAIN OUTCOME
      MEASUREMENTS: Self-report 10-item measure of surgeon confidence in managing
      psychosocial issues associated with trauma and perceived availability of support
      resources. RESULTS: Analyses, performed on the entire sample and repeated on the
      subset of 52 surgeons who responded to the survey at both times points, found
      surgeons at intervention sites experienced a significantly greater positive
      improvement (P < 0.05) in their (1) belief that they have strategies to help
      orthopaedic trauma patients change their psychosocial situation; (2) confidence
      in making appropriate referrals for orthopaedic trauma patients with psychosocial
      problems; and (3) belief that they have access to information to guide the
      management of psychosocial issues related to recovery. CONCLUSIONS: Initial data
      suggest that the establishment of the TCC program can improve surgeons' perceived
      availability of resources and their confidence in managing the psychosocial
      sequelae after injury. Further studies will be required to determine if this
      translates into beneficial patient effects. LEVEL OF EVIDENCE: Therapeutic Level
      II. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 28430721
TI  - Outcomes of Reverse Total Shoulder Arthroplasty for Proximal Humeral Fractures:
      Primary Arthroplasty Versus Secondary Arthroplasty After Failed Proximal Humeral
      Locking Plate Fixation.
AB  - OBJECTIVE: To compare the outcomes of reverse shoulder arthroplasty (RSA) between
      patients with failed proximal humeral locking plate (PHLP) fixation and those
      with acute fractures. DESIGN: Matched case-control study. SETTING: University
      hospital, Level I trauma center. PATIENTS: Thirty consecutive patients with
      fracture sequelae because of failed PHLP fixation (mean age 73) were age and sex
      matched to 30 patients with acute fracture (mean age 75). INTERVENTION: All
      patients underwent RSA. MAIN OUTCOME MEASUREMENTS: Constant, University of
      California Los Angeles (UCLA) and Disability of the Arm, Shoulder and Hand (DASH)
      scores. Radiological assessments were also performed. RESULTS: The mean
      postoperative follow-up was 3.2 (range, 2-5) years. All functional scores
      significantly improved from preoperative to postoperative (P = 0.001) in the
      sequelae group. Pain was relieved in all but one patient, and all but 2 patients
      were satisfied with their RSA. However, the functional outcomes at the last
      follow-up were significantly worse in the sequelae group compared with acute
      group in terms of adjusted Constant (P = 0.013), UCLA (P = 0.020) and DASH (P =
      0.048) scores, strength (P = 0.01), anterior forward (P = 0.021), and abduction
      (P = 0.007). Six patients (20%) in the sequelae group had complications including
      2 intraoperative (diaphyseal false passages), 2 early dislocations, 1 acromial
      fracture, and 1 aseptic loosening of glenoid component. Four of these patients
      were revised resulting all in a successful outcome at the last follow-up. In the
      acute group there was one intraoperative humeral fracture with no impact on the
      final outcome. CONCLUSIONS: Patients with failed PHLP fixation for fracture who
      were revised to RSA secondarily obtained marginally lower functional scores and
      higher complication rates compared with patients treated with primary RSA for
      fracture. However, patients who treated with secondary RSA had significant
      functional improvement and pain relief compared with their preoperative status,
      and most complications were manageable without a significant effect on final
      outcome. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 28430722
TI  - The Use of Liposomal Bupivacaine Administered With Standard Bupivacaine in Ankle
      Fractures Requiring Open Reduction Internal Fixation: A Single-Blinded Randomized
      Controlled Trial.
AB  - OBJECTIVES: To determine the efficacy of liposomal bupivacaine compared to
      placebo for postoperative pain control in patients undergoing operative fixation
      of ankle fractures. DESIGN: Prospective single-blinded randomized control trial.
      SETTING: Academic Medical Center. PATIENTS/PARTICIPANTS: After Institutional
      Review Board (IRB) approval, 76 patients who sustained an acute ankle fracture
      (OTA/AO 44A-C) requiring operative fixation met inclusion criteria. INTERVENTION:
      Patients were randomly assigned to 1 of 2 groups, control (local intraoperative
      sterile saline injection under general anesthesia) or interventional (local
      intraoperative liposomal bupivacaine and bupivacaine injection under general
      anesthesia). Injections were administered in a standardized fashion and included
      injection of a 1:1 mixture of a 40 mL solution consisting of 1.3% Exparel and
      sterile saline (interventional) or a 40 mL injection of normal saline (control)
      into the surrounding periosteal, peritendinous, surrounding muscles and
      subcutaneous tissue of the surgical incision(s). MAIN OUTCOME MEASUREMENTS: Pain
      medications administered and pain according to the Visual Analogue Scale was
      recorded at scheduled postoperative time points: 4, 24, 48, 72, and 336 hours (14
      days). RESULTS: Thirty-nine patients were randomized to the control group and 37
      to the interventional group (mean age = 42 +/- 15 years), with no statistically
      significant differences between groups with regards to severity of injury and
      patient demographics. Pain scores were significantly lower in the interventional
      group versus control up to 2 weeks after surgery. Percocet ingestion at 4 hours
      was significantly lower in the interventional group (0.7 vs. 1.3, P = 0.004),
      while it approached significance at 48 hours postoperatively (2.8 vs. 3.69, P =
      0.07). No other significant differences were noted for Percocet ingestion
      postoperatively at other time points assessed. The overall satisfaction with pain
      control was not statistically different between the 2 groups (P = 0.93).
      CONCLUSION: Local intraoperative infiltration of liposomal bupivacaine
      administered with standard bupivacaine for ankle fractures requiring Open
      Reduction Internal Fixation (ORIF) affords improved pain relief in the immediate
      postoperative period resulting in a reduction in Percocet ingestion, with
      resultant effects seen up to 2 days postoperatively. Continued investigation of
      this drug for use with extremity fractures is warranted. LEVEL OF EVIDENCE:
      Therapeutic Level I. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 28430723
TI  - Colpocleisis: A Survey of Current Practice Patterns.
AB  - BACKGROUND: Currently, there are no standard treatment guidelines for
      colpocleisis. Clinical practice varies widely for this safe and effective
      procedure. OBJECTIVE: The aim of this study was to evaluate the current practice
      patterns in the United States among surgeons who perform colpocleisis. METHODS: A
      27-item anonymous Web-based survey was sent to all practicing physicians
      affiliated with the American Urogynecologic Society. It consisted of questions
      regarding the demographic background of the physicians and their current practice
      as it relates to colpocleisis. RESULTS: Of the 1422 physicians contacted, 322
      responded (23%) to the questionnaire. Slightly more than half were female with an
      average time of 15 years in practice. The majority of respondents (79%) were
      urogynecologists. Most surgeons chose colpocleisis for its high success rate,
      short operating time, and low risk of complications. Approximately half of the
      providers performed both LeFort and total colpocleisis. Only 18% performed a
      routine hysterectomy at the time of surgery. Routine preoperative endometrial
      evaluation was preferred by 68% of the respondents, with 81% utilizing a
      transvaginal ultrasound first. Almost all providers would perform concomitant
      incontinence procedures, with 54% requiring a positive cough stress test and
      normal postvoid residual. CONCLUSIONS: There is variation in the current practice
      of colpocleisis in the United States. LeFort colpocleisis is most commonly
      performed, and routine hysterectomy is uncommon. Two thirds of surgeons evaluate
      the endometrium prior to surgery. Concomitant anti-incontinence procedures appear
      to be standard.

PMID- 28430725
TI  - Awareness Regarding Perineal Protection, Obstetric Anal Sphincter Injury, and
      Episiotomy Among Obstetrics and Gynecology Residents; Effects of an Educational
      Workshop.
AB  - OBJECTIVES: Appropriate perineal protection may reduce rates of obstetric anal
      sphincter injuries (OASIS). We sought to investigate the knowledge and attitudes
      of obstetrics and gynecology residents concerning perineal protection, OASIS, and
      episiotomy before and after an educational workshop. METHODS: This was an
      institutional review board-approved cross-sectional survey study of obstetrics
      and gynecology residents. Two experts in perineal protection, whose methods have
      been shown to reduce OASIS by 50%, provided 1 week of education. Residents were
      taught in hands-on workshops and labor and delivery wards. Residents were
      surveyed regarding experiences, knowledge, and opinions of perineal protection,
      OASIS, and episiotomy. Surveys were administered immediately before and after the
      workshop and at 3 months following. RESULTS: All 31 residents participated.
      Almost all (97%) felt it was possible to reduce the incidence of OASIS prior to
      the workshop. Statistically significant increases were noted following training
      in the number that felt it was "very effective" to use the 2-handed technique
      taught in the workshop (P = 0.002), as well as those that reported most commonly
      performing a mediolateral episiotomy (protective against OASIS, if used
      selectively) when episiotomy was indicated (P = 0.001). The percent that reported
      feeling "comfortable" or "very comfortable" performing episiotomies increased
      from 45% to 77% immediately after the workshop (P = 0.002); this declined to 55%
      at 3 months. A large majority (77%) reported that the workshop was beneficial;
      65% described an impact to patient care. CONCLUSIONS: A workshop targeting
      perineal protection improved awareness and changed clinical practice in this
      group of residents. Ongoing education regarding perineal protection and
      episiotomy may reinforce behavior modifications.

PMID- 28430724
TI  - The Effect of Lithotomy Position on Nerve Stretch: A Cadaveric Study.
AB  - OBJECTIVE: The objective of our study was to design a method to measure nerve
      stretch in cadaveric subjects and then use the method to assess femoral nerve
      stretch in the lithotomy position with varying degrees of flexion and extension.
      METHODS: A university-based, cadaveric observational study of femoral nerve
      stretch was conducted. In 6 cadaveric subjects, femoral nerve near the inguinal
      ligament was dissected in each cadaveric subject. The nerve was marked, and
      digital images of the nerve were obtained in the supine position and lithotomy
      position in both flexion and extension. Distances were calculated using the ratio
      of pixels to millimeter specific for each image. The average distance for each
      set of images was then used to calculate the percent change from supine for each
      position. RESULTS: We were able to assess nerve stretch using photo-editing
      software. For extended position, all nerves showed some degree of stretch with
      the mean percent change in nerve length being 10.35%. For all other positions,
      most showed a decrease of nerve length. There was not a significant relation
      between degree of extension and stretch (Pearson r, P < 0.05). CONCLUSIONS: Hip
      extension between 10 and 20 degrees consistently stretches the femoral nerve
      greater than 5%. The potential for femoral nerve stretch and avoiding hip
      extension should be considered when positioning a patient in lithotomy for
      surgical procedures.

PMID- 28430726
TI  - Vaginal Mesh Removal Outcomes: Eight Years of Experience at an Academic Hospital.
AB  - OBJECTIVES: The purpose of this study is to describe the clinical history leading
      up to and the outcomes after vaginal mesh removal surgery at an academic
      hospital. METHODS: A retrospective case series of patients who underwent vaginal
      mesh removal from 2008 to 2015 was conducted. Demographics, clinical history,
      physical examination, pre- and postoperative symptoms, and number and type of
      reoperations were abstracted. RESULTS: Between February 2008 and November 2015,
      83 patients underwent vaginal mesh removal surgery at our hospital. The median
      time interval from initial mesh placement to removal was 58 months (range, 0.4
      154 months). The most common preoperative symptoms were vaginal pain (n = 52,
      62%), dyspareunia (n = 46, 55%), and pelvic pain (n = 42, 50%). Intraoperative
      complications were infrequent (n = 3, 4%). Of patients presenting for follow-up
      within 4 to 6 weeks postoperatively, the most common symptoms were urinary
      incontinence (n = 15, 28%), vaginal pain (n = 7, 13%), buttock pain (n = 5, 9%),
      and urinary tract infection (n = 5, 9%). There were no identifiable risk factors
      to predict which patients would have persistent postoperative symptoms or who
      would require more than 1 mesh removal surgery. After vaginal mesh removal, 29
      patients (35%) required 1 or more reoperations, with 3 being the highest number
      of reoperations per patient. The total number of reoperations was 43, with a
      total of 63 individual procedures performed. Forty-four percent (n = 28) of the
      procedures were graft removals, 40% (n = 25) were pelvic organ prolapse surgeries
      (only native tissue repairs), and 16% (n = 10) were stress incontinence
      surgeries. More than 1 procedure was performed in 49% (n = 21) of the
      reoperations. CONCLUSIONS: Vaginal mesh removal surgery is safe; however, some
      patients require more than 1 procedure, and the risk factors for reoperations are
      unclear.

PMID- 28430727
TI  - Changing Referral Patterns to Urogynecology.
AB  - OBJECTIVE: The study aims to identify sources of and changes in referral patterns
      for pelvic floor disorders. METHODS: All new patient visits to urogynecology at
      our institution between January 2010 and December 2015 were identified. Patient
      demographics, referral source, insurance type, and visit diagnoses using ICD-9
      codes were abstracted. ICD-9 codes were grouped into 18 urogynecologic diagnoses.
      Data were analyzed using SPSS (Version 20; Chicago, IL). RESULTS: Five thousand
      seven hundred ninety-nine new patient visits were included in the analysis. The
      mean age was 54 +/- 17 years and 59% were Caucasian. Forty-four percent were
      referred by obstetrician/gynecologists (OB/GYNs), 32% by primary care providers
      (PCPs), 14% by self-referral, and 9% by other specialties. New patient visits
      increased overall by 280% over 6 years; self- and PCP referrals increased by 480%
      and 320%, respectively. In comparison, OB/GYN referrals increased by only 229%.
      Patients diagnosed with prolapse and stress incontinence were more likely to be
      referred by an OB/GYN (P < 0.001), whereas PCPs were more likely to refer for
      urinary tract infections (P < 0.005) and urgency urinary incontinence (P < 0.001)
      than OB/GYNs. CONCLUSIONS: Demand for pelvic floor specialists is growing
      quickly, with PCP and self-referrals outpacing referrals from obstetrician
      gynecologists to tertiary care urogynecology practices.

PMID- 28430728
TI  - The Impact of a Dedicated Robotic Team on Robotic-Assisted Sacrocolpopexy
      Outcomes.
AB  - BACKGROUND: Robotic-assisted sacrocolpopexy has been criticized for high cost. A
      strategy to increase operating room efficiency and decrease cost is
      implementation of a dedicated robotic team. Our objective was to determine if a
      dedicated robotic team decreases operative time. STUDY DESIGN: This institutional
      review board-approved retrospective cohort study included all robotic-assisted
      sacrocolpopexy performed from June 2010 to August 2015 by a single surgeon at 2
      institutions in 1 health system. One hospital had a dedicated robotic team,
      whereas the other did not. To assess baseline differences, chi and t tests were
      used. Multivariable linear regression identified factors impacting operative
      time. RESULTS: Eighty-eight robotic-assisted sacrocolpopexy cases met inclusion
      criteria. Subjects were primarily white (92.8%) and postmenopausal (85.5%) with
      stage III prolapse (71.1%). Mean age was 60.6 +/- 9.0 years, and BMI was 28.5 +/-
      5.1 kg/m. Seventeen cases (19.3%) had a dedicated team. In the 71 cases without a
      dedicated team, there were 16 different surgical technologist and no advanced
      practice providers. Groups had similar baseline characteristics (all P >
      0.05).Mean operative time for the dedicated team was significantly less (131.8 vs
      160.2 minutes, P < 0.001), a 17.7% time reduction. The decrease persisted on
      multivariable regression (beta = -25.98 minutes, P < 0.001) after adjusting for
      case order on the day (beta = -8.6 minutes, P = 0.002) and prior to hysterectomy
      (beta = -36.1 minutes, P < 0.001). Operative complications and prolapse
      recurrence were low overall and not different between the dedicated and
      nondedicated teams (0% vs 2.9%, P = 0.50; 0% vs 7.5%, P = 0.29). CONCLUSIONS: A
      dedicated robotic team during robotic-assisted sacrocolpopexy significantly
      decreased operative time by 26 minutes, a 17.7% reduction at our institution.

PMID- 28430729
TI  - Impact of Distance to Treatment Center on Care Seeking for Pelvic Floor
      Disorders.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of distance from
      residence to treatment center on access to care for female pelvic floor disorders
      at an academic institution. METHODS: A retrospective cross-sectional study was
      conducted of women seen for pelvic floor disorders at an academic institution
      from 2008 to 2014. Patient characteristics were extracted from charts.
      Geographical and US census data was obtained from public records and used to
      calculate distance from patient residence to physician office. Statistical
      analysis was performed using R Software (Version 0.98.1102) and Microsoft Excel
      (Version 14.4.7). Statistical significance was defined as a 2-sided P value of
      less than 0.05, and the chi test was used to determine associations of
      categorical variables. RESULTS: A total of 3015 patients were included in the
      analysis. The mean distance traveled was 93 miles. Thirty percent of patients
      traveled more than 50 miles. Many patients (43%) reported having the symptoms for
      more than 2 years. Patients who traveled farther were significantly more likely
      to be white, English-speaking, and with pelvic organ prolapse as primary
      complaint. These patients were more likely to plan surgery at the first visit
      than patients who traveled less far (29% vs 14%). Patients who traveled farther
      were also more likely to live in counties with a low percentage of persons older
      than 65 years and low percentage of female inhabitants. CONCLUSIONS: Women who
      travel the farthest for treatment of pelvic floor disorders have experienced the
      symptoms for longer duration and are more willing to plan surgery at
      presentation. These women also come from counties with fewer elderly women,
      suggesting future outreach care should focus on similar geographic areas.

PMID- 28430730
TI  - Comment on Chlorhexidine Keratitis.

PMID- 28430731
TI  - Commentary on Ultrasound Evaluation as a Complementary Test in Hidradenitis
      Suppurativa.

PMID- 28430732
TI  - Noninvasive RCM for Differentiation of Melanotic Macules From Melanocytic Lesions
      Blinded Evaluation of a Series of 42 Pigmented Macules.
AB  - BACKGROUND: Differentiation of melanotic macules from melanocytic lesions, most
      importantly of melanoma, is a common problem on clinical-dermoscopic examination.
      OBJECTIVE: To assess the value of noninvasive reflectance confocal microscopy
      (RCM) in the differential diagnosis of melanotic macules and melanocytic lesions.
      PATIENTS AND METHODS: Reflectance confocal microscopy images of 42 pigmented
      macules on mucocutaneous junctions of genitalia and lips, including 31 melanotic
      macules, 6 nevi, and 5 melanomas, were retrospectively and independently assessed
      in a blinded manner by one expert observer and 2 less experienced observers
      together. RESULTS: The authors differentiated 3 subtypes of melanotic macules; 2
      subtypes ("solar lentigo type" and regular subtype of "dendritic type" melanotic
      macules) could be classified with confidence as benign by all RCM investigators,
      comprising 64% of melanotic macules. The third subtype (irregular subtype of
      "dendritic type" melanotic macules; 36%) displaying RCM features overlapping with
      melanoma was difficult to differentiate and should be biopsied not to miss a
      melanoma. The RCM differentiation between melanotic macules and nevi was easily
      performed. CONCLUSION: RCM has the potential to increase the diagnostic accuracy
      in the noninvasive differentiation of pigmented macules on mucocutaneous
      junctions.

PMID- 28430734
TI  - Adding Volume for Reduction of Thick Lips in the Asian Patient.

PMID- 28430735
TI  - Sodium Tetradecyl Sulfate: A Review of Clinical Uses.
AB  - BACKGROUND: Sodium tetradecyl sulfate (STS) is Food and Drug Administration
      approved for treatment of varicose veins, but numerous other off-label
      applications have been reported. OBJECTIVE: To describe the clinical uses of STS,
      as well as efficacy and adverse effects. METHODS: Review of studies searchable on
      PubMed from 1938 to 2016 describing clinical uses of STS to determine efficacy
      and adverse effects associated with various applications. RESULTS: Sodium
      tetradecyl sulfate has shown efficacy in the treatment of varicose veins,
      telangiectasias, hemangioma, pyogenic granuloma, cherry angioma, Kaposi sarcoma,
      lymphangioma circumscriptum, digital mucous cyst, ganglion cyst, glomangioma,
      angiokeratoma of Fordyce, pseudocyst of the auricle, and verruca. Commonly
      reported side effects include pain, erythema, swelling, hyperpigmentation,
      telangiectatic matting, and ulceration. Serious side effects such as anaphylaxis,
      pulmonary embolism, stroke, and myocardial infarction have also been reported.
      Most sources were case reports and small prospective studies, as such the
      strength of data supporting many uses is limited by small sample sizes and lack
      of controls. CONCLUSION: Although not always the most effective method of
      treatment in off-label usage, use of STS has been frequently selected for a
      variety of applications for reasons of simplicity, low cost, lack of availability
      of technologically advanced equipment, and intricacies related to anatomic
      location.

PMID- 28430736
TI  - Vertical Lifting: A New Optimal Thread Lifting Technique for Asians.
AB  - BACKGROUND: With the evolution of facial rejuvenation methods, thread lifts have
      gained popularity among patients who seek cosmetic improvement. Absorbable wedge
      shaped polydioxanone (PDO) sutures are currently available, and they are
      extremely popular in the aesthetic clinics in Korea. In case of midface and
      mandibular jowl lift, threads are most often inserted in an oblique manner with
      vectors of rejuvenation directed toward the temple. However, specific
      characteristics of skeletal anatomy should be considered when deciding which
      technique to use in Asians. Herein, the authors introduce a vertical lifting
      technique most suitable for Asians, in which short (6 cm in length), wedge-shaped
      PDO sutures are inserted vertically downward in the anterior malar and submalar
      areas. OBJECTIVE: To describe a novel technique adopted to counteract the descent
      and laxity of the Asian face. The authors also aimed to assess the overall safety
      and efficacy of wedge-shaped PDO thread lift in facial rejuvenation. METHODS: A
      retrospective chart review was performed on cases of facial laxity treated with
      vertical thread lifting. A total of 39 Korean patients were included. All
      participants underwent a single treatment session. The results were assessed
      objectively using serial photography and subjectively based on the patients'
      satisfaction scores. Complications were also recorded. RESULTS: Most patients
      (89.7%) considered the results satisfactory. Consensus ratings by 2 independent
      dermatologists showed that the objective outcomes at the 6-month follow-up were
      largely categorized as very much improved (10.3%), much improved (43.6%), and
      improved (33.3%). The incidence of complications was low, and the complications
      were minor. CONCLUSION: Thread lifting with short, wedge-shaped PDO sutures is
      safe and effective for facial rejuvenation. The authors' vertical lifting
      technique has several advantages over the current approaches. First, the vectors
      directly oppose the vertical sagging of the face, which makes the technique
      highly efficient. The technique also carries a lower risk of accentuating the
      cheekbones, a feature which most Asians do not prefer.

PMID- 28430737
TI  - Laser Hair Removal in Alopecia Areata of the Scalp: A Novel Therapeutic Approach.

PMID- 28430738
TI  - Three-dimensional fractal analysis of 99mTc-MAA SPECT images in chronic
      thromboembolic pulmonary hypertension for evaluation of response to balloon
      pulmonary angioplasty: association with pulmonary arterial pressure.
AB  - OBJECTIVE: Balloon pulmonary angioplasty (BPA) is used for inoperable chronic
      thromboembolic pulmonary hypertension (CTEPH), but its effect cannot be evaluated
      noninvasively. We devised a noninvasive quantitative index of response to BPA
      using three-dimensional fractal analysis (3D-FA) of technetium-99m
      macroaggregated albumin (Tc-MAA) single-photon emission computed tomography
      (SPECT). PATIENTS AND METHODS: Forty CTEPH patients who underwent pulmonary
      perfusion scintigraphy and mean pulmonary arterial pressure (mPAP) measurement by
      right heart catheterization before and after BPA were studied. The total uptake
      volume (TUV) in bilateral lungs was determined from maximum intensity projection
      Tc-MAA SPECT images. Fractal dimension was assessed by 3D-FA. Parameters were
      compared before and after BPA, and between patients with post-BPA mPAP more than
      30 mmHg and less than or equal to 30 mmHg. Receiver operating characteristic
      analysis was carried out. RESULTS: BPA significantly improved TUV (595+/-204
      885+/-214 ml, P<0.001) and reduced the laterality of uptake (238+/-147-135+/-131
      ml, P<0.001). Patients with poor therapeutic response (post-BPA mPAP>=30 mmHg,
      n=16) showed a significantly smaller TUV increase (P=0.044) and a significantly
      greater post-BPA fractal dimension (P<0.001) than the low-mPAP group. Fractal
      dimension correlated with mPAP values before and after BPA (P=0.013 and 0.001,
      respectively). A post-BPA fractal dimension threshold of 2.4 distinguished
      between BPA success and failure with 75% sensitivity, 79% specificity, 78%
      accuracy, and area under the curve of 0.85. CONCLUSION: 3D-FA using Tc-MAA SPECT
      pulmonary perfusion scintigraphy enables a noninvasive evaluation of the response
      of CTEPH patients to BPA.

PMID- 28430739
TI  - Downstream indication to revascularization following hybrid cardiac PET/MRI:
      preliminary results.
AB  - BACKGROUND: Hybrid PET/MRI allows the acquisition of both fluorine-18
      fluorodeoxyglucose (F-FDG) PET and cardiac magnetic resonance (CMR) during one
      session. Whether this will result in different referral to coronary
      revascularization (CR) is unknown. We compared this new hybrid method with all
      nuclear/all-CMR methods in the assessment of viable myocardium and in downstream
      referral to CR. PATIENTS AND METHODS: Overall, 12 patients with rest perfusion
      defects on a single photon emission computed tomography (SPECT) were recruited
      for cardiac viability assessment using a PET/MRI device. Perfusion (SPECT and
      CMR), metabolism, late gadolinium enhancement (LGE), and contractility were
      compared using a 20-segments bull's eye for agreement. The patterns of
      ischemia/viability were compared between all-nuclear, all-CMR, and hybrid
      methods. Downstream CR was proposed after correlating findings to coronary
      angiography. RESULTS: The SPECT and CMR perfusion denoted poor agreement
      [agreement rate (AR): 60%; kappa: 0.191, P<0.004]. The added PET metabolism
      concurred in reclassifying 19.2% of segments with intermediate or unassessable
      LGE using the hybrid method. Overall, the all-CMR method showed better agreement
      with the hybrid method than the all-nuclear method for findings of normal (AR:
      100%, kappa: 1.00 vs. 65.8% %; kappa: 0.347, respectively; P<0.001), scar (AR:
      85%; kappa: 0.675 vs. 80.8%; kappa: 0.596, respectively; P<0.001), and ischemic
      segments (AR: 95.8%; kappa: 0.881 vs. 75.8%; kappa: 0.168, respectively;
      P<0.001). Downstream CR was proposed in four, 11, and 12 vessels by the all
      nuclear, all-CMR, or hybrid methods, respectively. CONCLUSION: Compared with all
      CMR, the hybrid method allowed the reclassification of 19.2% segments. Using CMR
      perfusion instead of SPECT perfusion had a significant impact on downstream
      target vessel revascularization.

PMID- 28430740
TI  - Low-dose computed tomography scans with automatic exposure control for patients
      of different ages undergoing cardiac PET/CT and SPECT/CT.
AB  - PURPOSE: This study aimed to evaluate the efficacy of automatic exposure control
      (AEC) in order to optimize low-dose computed tomography (CT) protocols for
      patients of different ages undergoing cardiac PET/CT and single-photon emission
      computed tomography/computed tomography (SPECT/CT). METHODS: One PET/CT and one
      SPECT/CT were used to acquire CT images for four anthropomorphic phantoms
      representative of 1-year-old, 5-year-old and 10-year-old children and an adult.
      For the hybrid systems investigated in this study, the radiation dose and image
      quality of cardiac CT scans performed with AEC activated depend mainly on the
      selection of a predefined image quality index. Multiple linear regression methods
      were used to analyse image data from anthropomorphic phantom studies to
      investigate the effects of body size and predefined image quality index on CT
      radiation dose in cardiac PET/CT and SPECT/CT scans. RESULTS: The regression
      relationships have a coefficient of determination larger than 0.9, indicating a
      good fit to the data. According to the regression models, low-dose protocols
      using the AEC technique were optimized for patients of different ages. In
      comparison with the standard protocol with AEC activated for adult cardiac
      examinations used in our clinical routine practice, the optimized paediatric
      protocols in PET/CT allow 32.2, 63.7 and 79.2% CT dose reductions for
      anthropomorphic phantoms simulating 10-year-old, 5-year-old and 1-year-old
      children, respectively. The corresponding results for cardiac SPECT/CT are 8.4,
      51.5 and 72.7%. CONCLUSION: AEC is a practical way to reduce CT radiation dose in
      cardiac PET/CT and SPECT/CT, but the AEC settings should be determined properly
      for optimal effect. Our results show that AEC does not eliminate the need for
      paediatric protocols and CT examinations using the AEC technique should be
      optimized for paediatric patients to reduce the radiation dose as low as
      reasonably achievable.

PMID- 28430741
TI  - Utility of 8 h and time decay-corrected acquisition scintigraphy with in-vitro
      labeled white blood cells for the diagnosis of osteoarticular infection.
AB  - INTRODUCTION: Except in the spine, labeled white-blood cell scintigraphy (WBCS)
      with image acquisition up to 24 h is the nuclear medicine test of choice for
      diagnosing osteoarticular infection. However, distinguishing between inflammation
      and infection is a challenge. OBJECTIVES: The first aim of this study was to
      verify earlier research studies that used 4 and 24 h time decay-corrected
      acquisition (TDCA) to differentiate infection from inflammation. The second aim
      was to analyze whether 8 h acquisition (1-day protocol) yielded similar results
      as 20-24 h acquisition. PATIENTS AND METHODS: This was an observational study of
      94 patients (22-86 years, 52 women) with suspected osteoarticular infection
      referred to nuclear medicine to confirm infection. WBCS and TDCA images were
      obtained at 30 min, 4 h, and 8 h after injection of the labeled leukocytes, with
      collection times of 5, 8, and 12 min, respectively. Scintigrams were classified
      into three protocols: protocol 1: experts read only 30 min and 4 h images;
      protocol 2: experts read the whole set of images (30 min, 4 h, and 8 h) with
      different pixel intensities (each image normalized to its own maximum activity);
      protocol 3: experts read the whole set of images with the same pixel intensity.
      Sensitivity, specificity, positive and negative predictive values, and accuracy
      were calculated. In patients with orthopedic implants, the interobserver
      reproducibility for visual analysis was calculated using the kappa index.
      RESULTS: Infection was confirmed in 26 cases. Sensitivity, specificity, positive
      predictive value, negative predictive value, accuracy, and kappa results were as
      follows: protocol 1: 92.3, 50.0, 41.4, 94.4, 61.7%, 0.79; protocol 2: 92.3, 94.1,
      85.7, 97.0, 93.6%, 0.80; protocol 3: 96.2, 97.1, 92.6, 98.5, 96.8%, 0.77.
      CONCLUSION: TDCA acquisition of WBCS at 8 h (1-day protocol) enables a faster
      diagnosis than 24 h acquisition. The use of TDCA with the same pixel intensity in
      all images enables an accurate diagnostic of osteoarticular infection, with a
      considerable interobserver agreement for all protocols.

PMID- 28430742
TI  - Utility of single-photon emission tomography/computed tomography for sentinel
      lymph node localization in breast cancer patients.
AB  - OBJECTIVES: Sentinel lymph node (SLN) mapping is currently a routine technique in
      breast cancer management and preoperative scintigraphic imaging plays a crucial
      role in the process of SLN detection. The guidelines recommend performing planar
      acquisition and optional single-photon emission tomography/computed tomography
      (SPECT/CT) imaging. The aim of this study was to verify whether routine
      performing of SPECT/CT in addition to planar imaging increases the sensitivity of
      SLN detection in patients with early-stage breast cancer. The secondary aims were
      to compare radionuclide SLN imaging with intraoperative SLN detection and
      identify clinical and histopathological factors affecting the SLN detection rate.
      MATERIALS AND METHODS: A total of 153 early-stage breast cancer patients
      underwent lymph node scintigraphy in the years 2007-2013. Breast cancer patients
      with staging T1-2N0M0 were included. Planar and SPECT/CT lymphoscintigraphy were
      performed on the day before the surgery. The data on presence or absence of SLN,
      their number and localization were recorded for both methods and compared with
      each other as well as with intraoperative blue dye staining and histopathological
      findings. RESULTS: SPECT/CT identified SLN in 119/153 and planar scintigraphy in
      114/153 patients. Identification rates were 77.7 and 74.5%, respectively.
      Intraoperative lymph node assessment identified SLN in 76/126 cases with an
      identification rate of 60.3%. Identification rates for second echelon lymph node
      were 34.6% for hybrid imaging and 21.2% for planar scintigraphy. Statistical
      analysis did not yield a significant difference in diagnostic accuracy between
      these methods; however, the Wilcoxon signed-rank test showed that SPECT/CT
      significantly increases SLN identification rate compared with planar scintigraphy
      and intraoperative detection. Histopathological examination of excised SLN showed
      that 22 nodes were metastatic. SPECT/CT visualized all of these, whereas planar
      imaging and intraoperative lymph node detection procedure visualized 19 and 18,
      respectively. No clinical and histopathological factors affecting SLN detection
      rate were identified. CONCLUSION: Hybrid SPECT/CT lymphatic mapping yields a high
      SLN detection rate in patients with early-stage breast cancer and provides lymph
      node localization details. It identifies more SLN than planar imaging and
      intraoperative SLN detection. However, its limited superiority over the remaining
      two methods does not support its routine use for SLN localization. We suggest
      using SPECT/CT for SLN detection in case of equivocal planar imaging results.

PMID- 28430743
TI  - MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by
      targeting B-cell lymphoma 2.
AB  - MicroRNAs (miRNAs) contribute toward tumorigenesis through the modulation of
      tumor-related genes. MiR-148a has been characterized as a tumor-suppressing miRNA
      and its downregulation has been reported in tumors of a variety of cancers.
      However, the functional role of miR-148a in breast cancer is not yet fully
      understood. Using both in-vitro and in-vivo models, we confirmed that miR-148a
      acts to inhibit the proliferation of breast cancer cells. Through the use of
      bioinformatic approaches in miRNA target prediction, we determined that B-cell
      lymphoma 2 (BCL-2) is a likely target of miR-148a. The overexpression and
      tumorigenic effects of BCL-2 have already been confirmed in cancerous tumors of
      the breast. A dual-luciferase assay was performed to confirm that miR-148a
      targets the 3'-untranslated region of BCL-2. In this study, we first
      characterized the downregulation of miR-148a in breast cancer tissues. We then
      found that restoring expression of miR-148a suppressed the expression of BCL-2 at
      the level of both mRNA and protein. Upregulation of miR-148a caused a subsequent
      reduction of proliferation and an increase in apoptosis. In conclusion, we have
      confirmed the role of miR-148a as a pivotal regulator in breast cancer through
      its targeting of BCL-2. This evidence strongly suggests that miR-148a could prove
      to be a novel therapeutic target in breast cancer.

PMID- 28430744
TI  - Activation of a c-Jun N-terminal kinase-mediated autophagy pathway attenuates the
      anticancer activity of gemcitabine in human bladder cancer cells.
AB  - The role of autophagy in the anticancer activity of gemcitabine (GEM) in bladder
      cancer is unclear. The aim of this study is to determine whether GEM activates
      autophagy, the role of autophagy in the anticancer activity of GEM, and the
      underlying mechanism by which GEM induces autophagy. Human bladder cancer cell
      lines T24 and BIU87 were treated with GEM in vitro. Cell viability was measured
      using the Cell Counting Kit-8 assay. Apoptosis was detected by annexin V assay
      and western blot. Autophagy was measured by western blot and transmission
      electron microscopy. c-Jun N-terminal kinase (JNK) activation was detected by
      western blot. Chemical inhibitors were used for intervention of JNK and
      autophagy. GEM killed bladder cancer cells, which was associated with apoptosis
      induction. Autophagy was effectively activated by GEM. Suppressing autophagy in
      GEM-treated cells significantly decreased cell viability, which was associated
      with increased apoptosis. GEM-induced JNK activation and suppressed B-cell
      lymphoma 2 expression. The JNK inhibitor SP600125 inhibited GEM-induced autophagy
      activation and increased GEM's cytotoxicity. GEM kills bladder cancer cells
      through apoptosis. Meanwhile, JNK-mediated autophagy was activated, which
      protects the cells against apoptosis. Therefore, inhibition of autophagy could be
      exploited to enhance the anticancer efficacy of GEM for treating bladder cancer.

PMID- 28430745
TI  - Bortezomib pharmacokinetics in tumor response and peripheral neuropathy in
      multiple myeloma patients receiving bortezomib-containing therapy.
AB  - The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with
      respect to the maximum response to bortezomib and bortezomib-induced peripheral
      neuropathy (BIPN) development was studied. Maximum response to subcutaneous
      bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35
      MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan
      prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples
      were collected for 3 h after dosing completion to obtain the maximum plasma
      concentration and area under the time-concentration curve during 3 h postdose
      (AUC0-3) in each patient. A total of 35 patients with complete data were analyzed
      and the overall response rate was 91.4%. Complete response (CR) was observed in
      42.9% patients. The maximum plasma concentration (Cmax) was significant for the
      CR rate in two different models [full model: odds ratio (OR)=1.092; P=0.038,
      final model: OR=1.081; P=0.038]. In addition, Cmax was associated with a
      progression-free survival advantage. Overall, 48.6% of patients developed BIPN
      including peripheral sensory neuropathy and neuralgia. The VMP-treated patients
      had a higher risk compared with the VD-treated patients (OR=21.662; P=0.029).
      Cmax had a tendency to affect the occurrence of BIPN (>=grade 2) (OR=1.064;
      P=0.092). In real-world clinical practice using bortezomib for MM patients, Cmax
      among pharmacokinetic factors significantly affected the achievement of CR. The
      VMP-treated patients showed vulnerability to BIPN, suggesting the necessity for
      more careful monitoring.

PMID- 28430746
TI  - Serial Radiographs Do Not Change the Clinical Course of Nonoperative Stable
      OTA/AO 44-B1 Ankle Fractures.
AB  - OBJECTIVE: To assess radiographic markers of ankle stability in stable OTA/AO 44
      B1 ankle fractures. DESIGN: Retrospective review. SETTING: Academic Level-I
      trauma hospital. PATIENTS: One hundred thirty-four patients with stable OTA/AO 44
      B1 (Danis-Weber B, Supination-External Rotation-II) ankle fractures.
      INTERVENTION: Analysis of mortise view radiographs at the time of initial
      evaluation and final follow-up. VARIABLES MEASURED: (1) medial clear space; (2)
      Mueller-Nose Distance. MAIN OUTCOME MEASURE: Change in radiographic measurements
      resulting in conversion to operative intervention. RESULTS: Patients followed up
      an average of 2.6 visits in our clinics (SD 1.06). Patients received an average
      of 11.2 individual radiographic images to evaluate their injury (SD 3.9, maximum
      29). No patients progressed to surgery in this cohort. Mean medial clear space at
      the time of injury was 3.4 mm (SD 0.8) and was 3.3 mm (SD 0.7) at the time of
      final follow-up (P = 0.1). Mean Mueller-Nose measurement at the time of injury
      was 3.5 mm (SD 1.0) and was 3.5 mm (SD 0.8) at the time of final follow-up (P =
      0.47). CONCLUSIONS: No patients with stable OTA/AO 44-B1 fractures proceeded to
      surgery for loss of tibiotalar reduction or any other cause. Radiographic
      relationships were conserved during the follow-up, and serial radiographs may not
      be needed when managing these patients. LEVEL OF EVIDENCE: Prognostic Level IV.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 28430747
TI  - Interprosthetic and Peri-Implant Fractures: Principles of Operative Fixation and
      Future Directions.
AB  - : Advances in medicine and orthopaedic implant technology have dramatically
      increased the number of patients sustaining interprosthetic, inter-, or peri
      implant fractures. For these complex clinical scenarios, there are currently no
      available treatment algorithms. In this review, we outline the principles,
      strategies, and techniques to obtain both successful reconstruction and maximum
      function. LEVEL OF EVIDENCE: Therapeutic Level V. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 28430749
TI  - Neonatal Cervical Osteomyelitis With Bilateral Upper Limb Paresis.
AB  - Neonatal cervical osteomyelitis is extremely rare, with only a few cases having
      been reported. We report a neonate with cervical osteomyelitis and extensive
      inflammation of the surrounded tissues that caused nerve root compression and
      upper limb paresis.

PMID- 28430748
TI  - Immunogenicity of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in
      Children From a Japanese Encephalitis Virus-endemic Region.
AB  - BACKGROUND: Japanese encephalitis (JE) is a major public health concern in Asia
      and poses a small but potentially fatal threat to travelers from nonendemic
      countries, including children. No JE vaccine for pediatric use has been available
      in Europe and the United States. METHODS: Age-stratified cohorts of children
      between 2 months and 17 years received 2 doses of Vero cell-derived inactivated
      JE virus vaccine (IXIARO; Valneva Austria GmbH, Vienna, Austria) administered 28
      days apart [<3 years, 0.25 mL (half adult dose); >=3 years, 0.5 mL (full adult
      dose)]. Immunogenicity endpoints were seroconversion rate, 4-fold increase in JE
      neutralizing antibody titer and geometric mean titer assessed 56 days and 7
      months after the first vaccination in 496 subjects of the intent-to-treat
      population. The immune response to JE virus at both time points was also analyzed
      according to prevaccination JE virus and dengue virus serostatus. RESULTS: At day
      56, seroconversion was attained in >=99.2% of subjects with age-appropriate
      dosing, 4-fold increases in titer were reported for 77.4%-100% in various age
      groups, and geometric mean titers ranged from 176 to 687, with younger children
      having the strongest immune response. At month 7, seroconversion was maintained
      in 85.5%-100% of subjects. Pre-existing JE virus immunity did not impact on
      immune response at day 56; however, it led to a better persistence of protective
      antibody titers at month 7. CONCLUSIONS: IXIARO is highly immunogenic at both
      doses tested in the pediatric population, leading to protective antibody titers
      at day 56 in >99% of subjects who received the age-appropriate dose.

PMID- 28430750
TI  - Elevated Immune Response Among Children 4 Years of Age With Pronounced Local
      Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis
      Vaccination.
AB  - BACKGROUND: In the Netherlands, acellular pertussis vaccines replaced the more
      reactogenic whole-cell pertussis vaccines. This replacement in the primary
      immunization schedule of infants coincided with a significant increase in
      pronounced local adverse events (AEs) in 4 years old children shortly after the
      administration of a fifth diphtheria, tetanus, acellular pertussis and
      inactivated polio (DTaP-IPV) vaccine. The objective of this study was to
      investigate possible differences in vaccine antigen-specific immune responses
      between children with and without a pronounced local AE after the fifth DTaP-IPV
      vaccination. METHODS: Blood was sampled in 2 groups of 4-year-olds: a case group
      reporting pronounced local swelling and/or erythema up to extensive limb swelling
      at the injection site (n = 30) and a control group (n = 30). Peripheral blood
      mononuclear cells were stimulated with individual vaccine antigens. Plasma
      antigen-specific IgG, IgG subclass and total IgE concentrations and T-cell
      cytokine [interferon-gamma, interleukin (IL)-13, IL-17 and IL-10] production by
      stimulated peripheral blood mononuclear cells were determined by multiplex bead
      based fluorescent multiplex immunoassays. RESULTS: In children with AEs,
      significantly higher total IgE and vaccine antigen-specific IgG and IgG4
      responses as well as levels of the T-helper 2 (Th2) cytokine IL-13 were found
      after pertussis, tetanus and diphtheria stimulation compared with controls.
      CONCLUSIONS: Children with pronounced local reactions show higher humoral and
      cellular immune responses. Acellular vaccines are known to skew toward more Th2
      responses. The pronounced local AEs may be associated with more Th2 skewing after
      the fifth DTaP-IPV vaccination, but other biologic factors may also impact the
      occurrence of these pronounced local reactions.

PMID- 28430751
TI  - Rhabdomyolysis Complicating Typhoid Fever in A Child and Review of the
      Literature.
AB  - Typhoid fever is an important cause of morbidity and mortality in the developing
      world, particularly in children, but is infrequently observed in the developed
      world and can occur in patients without a significant travel history.
      Rhabdomyolysis as a complication has rarely been reported, and never in a child.
      A child with Salmonella enterica serovar Typhi septicemia, complicated by
      rhabdomyolysis, encephalopathy and pancreatitis is described and all 15 reported
      cases to date are summarized.

PMID- 28430752
TI  - Re: "Respiratory Viral Infections and Coinfections Caused by Human
      Metapneumovirus in Children With Cancer".

PMID- 28430753
TI  - Impact of Chlorhexidine Cord Cleansing on Mortality, Omphalitis and Cord
      Separation Time Among Facility-Born Babies in Nepal and Bangladesh.
AB  - Guidance is needed regarding potential extension of the World Health Organization
      recommendation for cord cleansing with chlorhexidine to babies born in
      facilities. Among 3223 facility-born babies from Nepal and Bangladesh, mortality
      was approximately halved among those allocated to the intervention clusters
      [10.5/1000 vs. 19.4/1000; relative risk (RR): 0.54; 95% confidence interval: 0.30
      0.97]. In high-mortality settings, a single policy for home and facility births
      is warranted.

PMID- 28430755
TI  - Differentiating Delirium From Sedative/Hypnotic-Related Iatrogenic Withdrawal
      Syndrome: Lack of Specificity in Pediatric Critical Care Assessment Tools.
AB  - OBJECTIVES: To identify available assessment tools for sedative/hypnotic
      iatrogenic withdrawal syndrome and delirium in PICU patients, the evidence
      supporting their use, and describe areas of overlap between the components of
      these tools and the symptoms of anticholinergic burden in children. DATA SOURCES:
      Studies were identified using PubMed and EMBASE from the earliest available date
      until July 3, 2016, using a combination of MeSH terms "delirium," "substance
      withdrawal syndrome," and key words "opioids," "benzodiazepines," "critical
      illness," "ICU," and "intensive care." Review article references were also
      searched. STUDY SELECTION: Human studies reporting assessment of delirium or
      iatrogenic withdrawal syndrome in children 0-18 years undergoing critical care.
      Non-English language, exclusively adult, and neonatal intensive care studies were
      excluded. DATA EXTRACTION: References cataloged by study type, population, and
      screening process. DATA SYNTHESIS: Iatrogenic withdrawal syndrome and delirium
      are both prevalent in the PICU population. Commonly used scales for delirium and
      iatrogenic withdrawal syndrome assess signs and symptoms in the motor, behavior,
      and state domains, and exhibit considerable overlap. In addition, signs and
      symptoms of an anticholinergic toxidrome (a risk associated with some common PICU
      medications) overlap with components of these scales, specifically in motor,
      cardiovascular, and psychiatric domains. CONCLUSIONS: Although important studies
      have demonstrated apparent high prevalence of iatrogenic withdrawal syndrome and
      delirium in the PICU population, the overlap in these scoring systems presents
      potential difficulty in distinguishing syndromes, both clinically and for
      research purposes.

PMID- 28430754
TI  - Biomarkers for Early Acute Kidney Injury Diagnosis and Severity Prediction: A
      Pilot Multicenter Canadian Study of Children Admitted to the ICU.
AB  - OBJECTIVE: Acute kidney injury occurs early in PICU admission and increases risks
      for poor outcomes. We evaluated the feasibility of a multicenter acute kidney
      injury biomarker urine collection protocol and measured diagnostic
      characteristics of urine neutrophil gelatinase-associated lipocalin, interleukin
      18, and liver fatty acid binding protein to predict acute kidney injury and
      prolonged acute kidney injury. DESIGN: Prospective observational pilot cohort
      study. SETTING: Four Canadian tertiary healthcare PICUs. PATIENTS: Eighty-one
      children 1 month to 18 years old. Exclusion criteria were as follows: cardiac
      surgery, baseline severe kidney disease, and inadequate urine or serum for PICU
      days 1-3. INTERVENTIONS: PICUs performed standardized urine collection protocol
      to obtain early PICU admission urine samples, with deferred consent. MEASUREMENTS
      AND MAIN RESULTS: Study barriers and facilitators were recorded. Acute kidney
      injury was defined based on Kidney Disease: Improving Global Outcomes serum
      creatinine criteria (acute kidney injuryserum creatinine) and by serum creatinine
      and urine output criteria (acute kidney injuryserum creatinine+urine output)
      Prolonged acute kidney injury was defined as acute kidney injury duration of 48
      hours or more. PICU days 1-3 neutrophil gelatinase-associated lipocalin,
      interleukin-18, and liver fatty acid binding protein were evaluated for acute
      kidney injury prediction (area under the curve). Biomarkers on the first day of
      acute kidney injury attainment (day 1 acute kidney injury) were evaluated for
      predicting prolonged acute kidney injury. Eighty-two to 95% of subjects had urine
      collected from PICU days 1-3. Acute kidney injuryserum creatinine developed in 16
      subjects (20%); acute kidney injuryserum creatinine+urine output developed in 38
      (47%). On PICU day 1, interleukin-18 predicted acute kidney injuryserum
      creatinine with area under the curve=0.82, but neutrophil gelatinase-associated
      lipocalin and liver fatty acid binding protein predicted acute kidney injuryserum
      creatinine with area under the curve of less than or equal to 0.69; on PICU day
      2, area under the curve was higher (not shown). Interleukin-18 and liver fatty
      acid binding protein on day 1 acute kidney injury predicted prolonged acute
      kidney injuryserum creatinine (area under the curve=0.74 and 0.83, respectively).
      When acute kidney injuryserum creatinine+urine output was used to define acute
      kidney injury, biomarker area under the curves were globally lower. CONCLUSIONS:
      Protocol urine collection to procure early admission samples is feasible.
      Individual biomarker acute kidney injury prediction performance is highly
      variable and modest. Larger studies should evaluate utility and cost
      effectiveness of using early acute kidney injury biomarkers.

PMID- 28430756
TI  - Does pregnancy influence melanoma prognosis? A meta-analysis.
AB  - The literature has not been able to conclude whether pregnancy influences the
      prognosis of melanoma. The aim of this study was to explore the prognosis of
      melanoma diagnosed during pregnancy or post partum [pregnancy-associated melanoma
      (PAM)] compared with melanoma in female patients who were not pregnant. We
      systematically searched for studies of female patients with melanoma that
      reported outcomes related to survival. Fifteen eligible studies were found.
      Overall, PAM was associated with a 17% higher mortality compared with melanoma
      diagnosed in female patients who were not pregnant (hazard ratio=1.17, 95%
      confidence interval: 1.03-1.33, P=0.02). The heterogeneity associated with this
      test was moderate (P=0.07; I=38%). PAM was also associated with a 50% higher
      recurrence rate compared with melanoma not associated with pregnancy (hazard
      ratio=1.50, 95% confidence interval: 1.19-1.90, P<0.001). The heterogeneity
      associated with this test was low (P=0.69; I=0%). A limitation of this meta
      analysis is the definition of PAM, which is not unanimous among the studies
      included. Our results indicate that PAM is associated with a worse prognosis than
      melanoma not related to pregnancy, both in terms of overall survival and disease
      free survival. On the basis of our data, we anticipate that the survival
      difference we report here will be further amplified with the addition of future
      well-carried out studies. We suggest that detection of PAM requires particular
      awareness by healthcare professionals.

PMID- 28430757
TI  - Public Goods, NIH Funding, and Civic Literacy.

PMID- 28430758
TI  - The Refractive Error of Professional Baseball Players.
AB  - PURPOSE: High levels of visual acuity are required to hit a baseball effectively.
      Research has shown that any decrease in vision is likely caused by low-order
      optical aberrations. This study is designed to validate the SVOne autorefractor,
      and describe the amount and type, of low-order optical aberrations present in a
      large cohort of professional baseball players. METHODS: A retrospective chart
      review on the 608 Major League Baseball players evaluated during the 2016 Spring
      Training Season was performed. Results for a subset of players who had both
      manifest refraction as well as autorefraction were calculated. Subsequently,
      after determining the accuracy of the autorefraction system in this population,
      refractive results for the entire population were determined. RESULTS: There was
      a borderline statistically significant difference in mean spherical refractive
      error (M) between the manifest refraction and the SVOne auto refraction (-0.273D
      in the manifest refraction method vs. -0.503D in the SVOne method, P = .06) in
      the subset of athletes who underwent both tests. Additionally, there was no
      difference in the J0 or J45 cylindrical component vectors for each method. For
      the entire eligible population, the SVOne autorefraction system found a mean
      spherical refractive error (M) of -0.228D, a J0 value of -0.013D, and a J45 value
      of -0.040D. CONCLUSIONS: These data suggest that the SVOne autorefraction system
      is generally able to measure the refractive error in the baseball population. The
      system was slightly biased, often reporting more myopia in myopic subjects. Thus,
      careful evaluation of the refractive status of these athletes coupled with
      careful subjective refractive correction for those with less than average vision
      for baseball is strongly suggested.

PMID- 28430759
TI  - Evaluation of guidelines for injured children at high risk for venous
      thromboembolism: A prospective observational study.
AB  - BACKGROUND: Pharmacologic prophylaxis for venous thromboembolism (VTE) is a
      widely accepted practice in adult trauma patients to prevent associated morbidity
      and mortality. However, VTE prophylaxis has not been standardized in injured
      pediatric patients. Our institution identified factors potentially associated
      with a high risk of VTE in critically injured children that led to prospective
      implementation of VTE prophylaxis guidelines. We hypothesize that the guidelines
      are accurate in predicting children at risk for VTE. METHODS: Data were
      prospectively collected on injured children from August 2010 to August 2015.
      Pharmacologic prophylaxis was indicated for patients identified by the guidelines
      as high risk for VTE. Prophylaxis was deferred and a screening ultrasound was
      performed if the high-risk VTE patients were also at high risk for bleeding. To
      assess the accuracy of predicting confirmed cases of VTE, stepwise logistic
      regression analysis was used to measure the association of individual risk
      factors with VTE controlling for age (>=13 years). A receiver operating
      characteristic curve measured the accuracy of the final model to predict a VTE.
      RESULTS: Of 4,061 trauma patients, 588 were admitted to the ICU, with the
      guidelines identifying 199 as high risk for VTE. VTE occurred in 3.9% (23/588) of
      the ICU population and 10% (20/199) of the high risk group. The median age of VTE
      patients in the ICU was 9.7 years. Statistically significant predictors (p <
      0.05) of VTE in the multivariate model included presence of a central venous
      catheter (OR = 5.2), inotropes (OR = 7.7), immobilization (OR = 5.5), and a
      Glasgow Coma Scale of <9 (OR = 1.3). The area under receiver operating
      characteristic curve of this model was 0.92, demonstrating its excellent
      predictive ability. CONCLUSION: Specific clinical factors in critically injured
      children are associated with a high risk for VTE. Incorporating these risk
      factors in VTE prophylaxis guidelines facilitates more accurate risk
      stratification and may allow for improved VTE prevention in pediatric trauma.
      LEVEL OF EVIDENCE: Prognostic study, level II.

PMID- 28430761
TI  - Featured Articles for CME Credit May 2017.

PMID- 28430760
TI  - Resuscitative endovascular balloon occlusion of the aorta or resuscitative
      thoracotomy with aortic clamping for noncompressible torso hemorrhage: A
      retrospective nationwide study.
AB  - BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is
      an emerging treatment for noncompressible torso hemorrhage. It remains unclear if
      REBOA is superior to resuscitative thoracotomy with aortic cross-clamping (RT) in
      terms of improving outcomes. This study compared in-hospital outcomes between
      REBOA and RT in trauma patients with uncontrolled hemorrhagic shock, using data
      from a national inpatient database in Japan. METHODS: Using the Diagnosis
      Procedure Combination database, we identified patients who received REBOA or RT
      within 1 day after admission from July 1, 2010, to March 31, 2014. We excluded
      those with penetrating thoracic injuries. Propensity score-adjusted analyses were
      performed to compare in-hospital mortality and other in-hospital outcomes.
      RESULTS: Eligible patients (n = 259) were classified into the REBOA group (n =
      191) or the RT group (n = 68). In the propensity score-adjusted Cox regression
      analysis, the two groups did not differ significantly with respect to in-hospital
      mortality (hazard ratio, 0.94; 95% confidence interval, 0.60-1.48). There were
      also no significant differences between the groups in ventilator-free days,
      intensive care unit-free days, total amount of fluid infusion within 1 day after
      admission, total amount of transfusion within 1 day after admission, or total
      hospitalization costs. CONCLUSION: In this retrospective nationwide study, in
      hospital outcomes were not significantly different between REBOA and RT in trauma
      patients with uncontrolled hemorrhagic shock. LEVEL OF EVIDENCE: Therapeutic/care
      management, level III.

PMID- 28430763
TI  - Protective Effect of Pinitol Against Inflammatory Mediators of Rheumatoid
      Arthritis via Inhibition of Protein Tyrosine Phosphatase Non-Receptor Type 22
      (PTPN22).
AB  - BACKGROUND The aim of the current study was to explore the anti-arthritic effect
      of pinitol via assessing its effect on various inflammatory mediators and its
      possible mechanism of action. MATERIAL AND METHODS We assessed the anti-arthritic
      effect of pinitol in a formaldehyde- and CFA-induced arthritic model in Wistar
      Swiss albino strain rats divided into 6 groups. The rats received different doses
      of pinitol and indomethacin for 28 days. The arthritic index and body weight were
      determined at regular intervals, together with hepatic, hematological, and
      antioxidant parameters. The expression of proinflammatory cytokines (e.g., IL-6,
      TNF-alpha, and IL-1beta) and inflammatory mediators (e.g., COX-2 and VEGF) were
      also estimated with histopathological evaluation of the joint tissue of rats. A
      docking study of pinitol with PTPN22 was also carried out. RESULTS The CFA
      induced model rats developed redness and nodules in the tail and front paws, and
      the arthritic control (AC) group rats showed similar symptoms, which were
      decreased by pinitol administration. The body weight of AC group rats was
      decreased, while pinitol-treated rats showed considerably increased body weight.
      Hematological, hepatic, and antioxidant parameters were altered by pinitol in a
      dose-dependent manner. Pinitol significantly decreased the elevated concentration
      of proinflammatory cytokines and inflammatory mediators, with improvement in
      histopathological condition. The docking study suggested that pinitol efficiently
      interacted with PTPN22 via Arg59, Tyr60, Leu106, and Lys138 by creating close
      interatomic hydrogen bonds and hydrophobic contacts. CONCLUSIONS Pinitol showed
      anti-arthritic effects via reduction of proinflammatory cytokines and
      inflammatory mediators via inhibition of PTPN22.

PMID- 28430764
TI  - Medwave?s editorial history, policies and guidelines: 3. Section policies.
AB  - This article is the third of a series of four editorials that report on Medwave?s
      policies, including section policies, formal requisites according to article
      type, and guidelines for reviewers and authors, with special emphasis on
      publication and research ethics. The journal believes that it is important to
      publish its policies in the format of editorials in order to facilitate and
      ensure dissemination to our broader readership. This editorial describes the
      types of articles that the journal publishes, such as primary studies, review
      articles, case reports, letters, and commentaries, among others.

PMID- 28430765
TI  - Breastfeeding knowledge of health professionals working in municipal healthcare
      centers in Maipu, Chile.
AB  - INTRODUCTION: Healthcare provider's knowledge has been identified as a factor
      associated with clinical practice skills and exclusive breastfeeding prevalence.
      OBJECTIVES: To evaluate the level of knowledge and training in breastfeeding of
      healthcare provider's that work in family healthcare centers of Maipu, Chile,
      (midwifes, physicians, nurses and nutritionists). To determine association among
      level of knowledge, profession and breastfeeding training. METHODS: Quantitative,
      cross-sectional, analytical study. Participants were healthcare professionals
      regularly participating in healthy child exams of six month old babies. We used a
      validated survey based on the "Ten steps for successful breastfeeding".
      Statistical analyses included frequencies, percentages, measures of central
      tendency as well as the association among level of knowledge, profession and
      training in breastfeeding. RESULTS: Results showed that of the total number of
      participants (n=78), 42.2% classified as "average", 3.8% as "poor" and near 50%
      as "good" or "very good" knowledge. Nutritionists obtained the best scores in
      knowledge about breastfeeding with 50% of "very good", followed by nurses and
      midwifes, with 39% and 35% respectively. On the other hand, most physicians
      obtained "good" (65.4%) and only 7.7% "very good". Only 33% had had breastfeeding
      training at some point of their lives, and 6.4% had had one training session in
      the last year. We highlight that 34.6 to 42.3% of those who obtained "good" and
      "very good" scores had had breastfeeding training. Knowledge level was directly
      associated with breastfeeding training (p=0.033) and healthcare profession
      (p=0.019). CONCLUSION: Healthcare professionals have different levels of
      breastfeeding knowledge. Breastfeeding training sessions significantly increase
      knowledge, which could improve breastfeeding prevalence.

PMID- 28430766
TI  - Linear immunoglobulin A dermatosis: A case report.
AB  - We present the case of a sixty five year old woman with two months history of
      pruritus and hyperpigmented annular lesions on the trunk, buttocks and upper
      extremities. In addition, she presents vesicles with healthy skin on the basis,
      in the flexor aspect of wrists. No evidence of mucosal involvement. Histological
      study showed subepidermal vesicular dermatitis with inflammatory infiltrate of
      neutrophils and eosinophils. Direct immunofluorescence evidenced linear and
      continuous deposition of immunoglobulin A in basement membrane zone, compatible
      with linear immunoglobulin A disease.

PMID- 28430767
TI  - Are steroids effective in toxic epidermal necrolysis and Stevens-Johnson
      syndrome?
AB  - Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe adverse skin
      reactions to medications and infections. Steroids are described as a therapeutic
      alternative, but their use is still controversial. To answer this question, we
      searched in Epistemonikos database, which is maintained by screening multiple
      information sources. We identified four systematic reviews including 11 primary
      studies answering the question of interest. We extracted data, conducted a meta
      analysis and generated a summary of findings table using the GRADE approach. We
      concluded it is not clear whether steroids reduce mortality or hospital stay in
      toxic epidermal necrolysis and Stevens-Johnson syndrome because the certainty of
      the evidence is very low.

PMID- 28430768
TI  - National scientific congress of medical students: how much do the Peruvian
      universities support?

PMID- 28430769
TI  - Scientific student research in tune with current trends.

PMID- 28430770
TI  - Medwave?s editorial history, policies and guidelines: 2. Editorial policies.
AB  - This article is the second of a series of four editorials that report on
      Medwave?s policies, including section policies, formal requisites according to
      article type, and guidelines for reviewers and authors, with special emphasis on
      publication and research ethics. The journal believes that it is important to
      publish its policies in the format of editorials in order to facilitate and
      ensure dissemination to our broader readership. This editorial refers to the
      importance of using reporting guidelines, values and principles, peer review
      process, authorship issues and publication ethics.

PMID- 28430771
TI  - Medwave?s editorial history, policies and guidelines: 4. Author instructions and
      journal guidelines.
AB  - This article is the last of a series of four editorials that report on Medwave?s
      policies, including section policies, formal requisites according to article
      type, and guidelines for reviewers and authors, with special emphasis on
      publication and research ethics. The journal believes that it is important to
      publish its policies in the format of editorials in order to facilitate and
      ensure dissemination to our broader readership. This editorial focuses on author
      instructions and again touches upon publication ethics.

PMID- 28430772
TI  - Medwave?s editorial history, policies and guidelines: 1. Description.
AB  - This article is the first of a series of four editorials that report on Medwave?s
      policies, including section policies, formal requisites according to article
      type, and guidelines for reviewers and authors, with special emphasis on
      publication and research ethics. The journal believes that it is important to
      publish its policies in the format of editorials in order to facilitate and
      ensure dissemination to our broader readership. This editorial refers to the
      history of the journal from foundation onwards, purpose and scope, mission, open
      access policy, indexation, among other important aspects.

PMID- 28430774
TI  - Is nintedanib effective for idiopathic pulmonary fibrosis?
AB  - Idiopathic pulmonary fibrosis has poor prognosis and effective therapies are
      scarce. In the search for treatments that can modify the course of the disease,
      nintedanib (BIBF 1120), a tyrosine kinase inhibitor, has emerged as an
      alternative. However, its role is still unclear. To answer this question, we
      searched in Epistemonikos database, which is maintained by screening multiple
      sources of information. We identified seven systematic reviews including seven
      randomized trials overall. We extracted data, conducted a meta-analysis and
      generated a summary of findings table using the GRADE approach. We concluded
      nintedanib probably decreases the risk of acute exacerbations, and might reduce
      mortality in idiopathic pulmonary fibrosis. On the other hand, it is probably not
      associated with serious adverse events.

PMID- 28430773
TI  - Is dexamethasone as effective as other corticosteroids for acute asthma
      exacerbation in children?
AB  - Dexamethasone has been proposed as an alternative in the treatment of acute
      asthma exacerbation in children. It allows shortening the duration of treatment,
      reducing costs and adverse effects. However, it is not clear whether its efficacy
      is similar to the traditional steroid regimen. To answer this question, we
      searched in Epistemonikos database, which is maintained by screening multiple
      information sources. We identified six systematic reviews including 10 randomized
      trials. We extracted data, conducted a meta-analysis and generated a summary of
      findings table using the GRADE approach. We concluded dexamethasone has probably
      fewer adverse effects than others corticosteroids, and might be equally effective
      in reducing hospitalizations and revisits.

PMID- 28430775
TI  - Early career investigator highlight.

PMID- 28430776
TI  - Aminoazo dye-protein-adduct enhances inhibitory effect on digestibility and
      damages to Gastro-Duodenal-Hepatic axis.
AB  - 4-Dimethylaminoazobenzene (DAB, methyl yellow, or butter yellow), a human
      carcinogen, has been banned for use in foods since 1988. In 2014, DAB
      adulteration in Tofu occurred in Taiwan. We hypothesize that DAB can form
      [DAB*SBP]adduct adduct with soybean protein (SBP) which could damage Gastro
      Duodenal-Hepatic axis. Sprague-Dawley rats gavage fed [DAB*SBP]adduct adduct
      revealed severely reduced body weight and damaged duodenum, liver, hepatic
      mitochondria, and spleen. Hepatic levels of glutathione and ATP were severely
      reduced. Serum GOT and GPT were substantially elevated. Analysis by the
      adsorption isotherm clearly revealed DAB formed very stable [DAB*SBP]adduct
      adduct at 1:1 molar ration (Phase A). The equilibrium constant of this colloidal
      adduct [DAB*SBP]adduct was KeqA = ?, behaving as the most stable and toxic
      species. At higher protein concentration (Phase C) it formed conjugate
      [DAB*SBPgross]conjugate, with KeqC = 3.23*10-2 mg/mL, implicating a moderately
      strong adsorption. The in vitro pepsin digestibility test showed apparently
      reduced digestibility by 27% (by Ninhydrin assay) or 8% (by Bradford assay).
      Conclusively, this is the first report indicating that [DAB*SBP]adduct
      potentially is capable to damage the Gastro-Duodenal-Hepatic axis.

PMID- 28430777
TI  - Correction: The Subclonal Architecture of Metastatic Breast Cancer: Results from
      a Prospective Community-Based Rapid Autopsy Program "CASCADE".
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1002204.].

PMID- 28430778
TI  - A no film slot blot for the detection of developing P. falciparum oocysts in
      mosquitoes.
AB  - Non-microscopy-based assays for sensitive and rapid detection of Plasmodium
      infection in mosquitoes are needed to allow rapid and high throughput measurement
      of transmission intensity and malaria control program effectiveness. Here, we
      report on a modified enhanced chemiluminescence-based slot blot assay for
      detection of Plasmodium falciparum (Pf) circumsporozite protein (PfCSP) expressed
      on parasite oocysts developing inside the mosquito midgut. This modified assay
      has several novel features that include eliminating the need for exposure to
      autoradiography (AR) film, as well as utilizing a novel high affinity anti-CSP
      antibody, and optimizing assay procedures resulting in significant reduction in
      the time required to perform the assay. The chemiluminescent signal for the
      detection of PfCSP in mosquito samples was captured digitally utilizing the C
      Digit blot scanner that, allowed the detection of 0.01 pg of recombinant P.
      falciparum CSP and as few as 0.02 P. falciparum oocysts in a little over two
      hours. The earlier ECL-SB detected rCSP and oocysts and took approximately 5 h to
      perform. Whole mosquito lysates from both high and low prevalence-infected
      mosquito populations were prepared and evaluated for PfCSP detection on the ECL
      SB by both AR film and digital data capture and analysis. There was a 100%
      agreement between the AR film and the C-Digit scanner methods for PfCSP detection
      in randomly sampled mosquitoes. This novel "No Film" Slot Blot assay obviates the
      need for AR film exposure and development and significantly reduces the assay
      time enabling widespread use in field settings.

PMID- 28430779
TI  - A coevolution analysis for identifying protein-protein interactions by Fourier
      transform.
AB  - Protein-protein interactions (PPIs) play key roles in life processes, such as
      signal transduction, transcription regulations, and immune response, etc.
      Identification of PPIs enables better understanding of the functional networks
      within a cell. Common experimental methods for identifying PPIs are time
      consuming and expensive. However, recent developments in computational approaches
      for inferring PPIs from protein sequences based on coevolution theory avoid these
      problems. In the coevolution theory model, interacted proteins may show
      coevolutionary mutations and have similar phylogenetic trees. The existing
      coevolution methods depend on multiple sequence alignments (MSA); however, the
      MSA-based coevolution methods often produce high false positive interactions. In
      this paper, we present a computational method using an alignment-free approach to
      accurately detect PPIs and reduce false positives. In the method, protein
      sequences are numerically represented by biochemical properties of amino acids,
      which reflect the structural and functional differences of proteins. Fourier
      transform is applied to the numerical representation of protein sequences to
      capture the dissimilarities of protein sequences in biophysical context. The
      method is assessed for predicting PPIs in Ebola virus. The results indicate
      strong coevolution between the protein pairs (NP-VP24, NP-VP30, NP-VP40, VP24
      VP30, VP24-VP40, and VP30-VP40). The method is also validated for PPIs in
      influenza and E.coli genomes. Since our method can reduce false positive and
      increase the specificity of PPI prediction, it offers an effective tool to
      understand mechanisms of disease pathogens and find potential targets for drug
      design. The Python programs in this study are available to public at URL
      (https://github.com/cyinbox/PPI).

PMID- 28430780
TI  - The importance of standardization for biodiversity comparisons: A case study
      using autonomous reef monitoring structures (ARMS) and metabarcoding to measure
      cryptic diversity on Mo'orea coral reefs, French Polynesia.
AB  - The advancement of metabarcoding techniques, declining costs of high-throughput
      sequencing and development of systematic sampling devices, such as autonomous
      reef monitoring structures (ARMS), have provided the means to gather a vast
      amount of diversity data from cryptic marine communities. However, such increased
      capability could also lead to analytical challenges if the methods used to
      examine these communities across local and global scales are not standardized.
      Here we compare and assess the underlying biases of four ARMS field processing
      methods, preservation media, and current bioinformatic pipelines in evaluating
      diversity from cytochrome c oxidase I metabarcoding data. Illustrating the
      ability of ARMS-based metabarcoding to capture a wide spectrum of biodiversity,
      3,372 OTUs and twenty-eight phyla, including 17 of 33 marine metazoan phyla, were
      detected from 3 ARMS (2.607 m2 area) collected on coral reefs in Mo'orea, French
      Polynesia. Significant differences were found between processing and preservation
      methods, demonstrating the need to standardize methods for biodiversity
      comparisons. We recommend the use of a standardized protocol (NOAA method)
      combined with DMSO preservation of tissues for sessile macroorganisms because it
      gave a more accurate representation of the underlying communities, is cost
      effective and removes chemical restrictions associated with sample
      transportation. We found that sequences identified at >= 97% similarity increased
      more than 7-fold (5.1% to 38.6%) using a geographically local barcode inventory,
      highlighting the importance of local species inventories. Phylogenetic approaches
      that assign higher taxonomic ranks accrued phylum identification errors (9.7%)
      due to sparse taxonomic coverage of the understudied cryptic coral reef community
      in public databases. However, a >= 85% sequence identity cut-off provided more
      accurate results (0.7% errors) and enabled phylum level identifications of 86.3%
      of the sequence reads. With over 1600 ARMS deployed, standardizing methods and
      improving databases are imperative to provide unprecedented global baseline
      assessments of understudied cryptic marine species in a rapidly changing world.

PMID- 28430781
TI  - An unmodified wobble uridine in tRNAs specific for Glutamine, Lysine, and
      Glutamic acid from Salmonella enterica Serovar Typhimurium results in
      nonviability-Due to increased missense errors?
AB  - In the wobble position of tRNAs specific for Gln, Lys, and Glu a universally
      conserved 5-methylene-2-thiouridine derivative (xm5s2U34, x denotes any of
      several chemical substituents and 34 denotes the wobble position) is present,
      which is 5-(carboxy)methylaminomethyl-2-thiouridine ((c)mnm5s2U34) in Bacteria
      and 5-methylcarboxymethyl-2-thiouridine (mcm5s2U34) in Eukarya. Here we show that
      mutants of the bacterium Salmonella enterica Serovar Typhimurium LT2 lacking
      either the s2- or the (c)mnm5-group of (c)mnm5s2U34 grow poorly especially at low
      temperature and do not grow at all at 15 degrees C in both rich and glucose
      minimal media. A double mutant of S. enterica lacking both the s2- and the
      (c)mnm5-groups, and that thus has an unmodified uridine as wobble nucleoside, is
      nonviable at different temperatures. Overexpression of [Formula: see text]
      lacking either the s2- or the (c)mnm5-group and of [Formula: see text] lacking
      the s2-group exaggerated the reduced growth induced by the modification
      deficiency, whereas overexpression of [Formula: see text] lacking the mnm5-group
      did not. From these results we suggest that the primary function of cmnm5s2U34 in
      bacterial [Formula: see text] and mnm5s2U34 in [Formula: see text] is to prevent
      missense errors, but the mnm5-group of [Formula: see text] does not. However,
      other translational errors causing the growth defect cannot be excluded. These
      results are in contrast to what is found in yeast, since overexpression of the
      corresponding hypomodified yeast tRNAs instead counteracts the modification
      deficient induced phenotypes. Accordingly, it was suggested that the primary
      function of mcm5s2U34 in these yeast tRNAs is to improve cognate codon reading
      rather than prevents missense errors. Thus, although the xm5s2U34 derivatives are
      universally conserved, their major functional impact on bacterial and eukaryotic
      tRNAs may be different.

PMID- 28430782
TI  - Predictors of falls and mortality among elderly adults with traumatic brain
      injury: A nationwide, population-based study.
AB  - BACKGROUND: Elderly adults are at particular risk of sustaining a traumatic brain
      injury (TBI), and tend to suffer worse outcomes compared to other age groups.
      Falls are the leading cause of TBI among the elderly. METHODS: We examined
      nationwide trends in TBI hospitalizations among elderly adults (ages 65 and
      older) between April 2006 and March 2011 using a population-based database that
      is mandatory for all hospitals in Canada. Trends in admission rates were analyzed
      using linear regression. Predictors of falls and in-hospital mortality were
      identified using logistic regression. RESULTS: Between 2006 and 2011, there were
      43,823 TBI hospitalizations resulting in 6,939 deaths among elderly adults in
      Canada. Over the five-year study period, the overall rate of TBI admissions
      increased by an average of 6% per year from 173.2 to 214.7 per 100,000, while the
      rate of fall-related TBI increased by 7% annually from 138.6 to 179.2 per
      100,000. There were significant trends towards increasing age and comorbidity
      level (p<0.001 and p = 0.002). Advanced age, comorbidity, and injury severity
      were independent predictors of both TBI-related falls and mortality on
      multivariate analysis. CONCLUSION: Prevention efforts should be targeted towards
      vulnerable demographics including the "older old" (ages 85 and older) and those
      with multiple medical comorbidities. Additionally, hospitals and long-term care
      facilities should be prepared to manage the burgeoning population of older
      patients with more complex comorbidities.

PMID- 28430783
TI  - Shigella dysenteriae infection activates proinflammatory response through beta
      catenin/NF-kappaB signaling pathway.
AB  - Shigella dysenteriae (S.dysenteriae) the causative agent of bacillary dysentery
      invades the human colonic epithelium resulting in severe intestinal inflammatory
      response and epithelial destruction. However, the mechanism by which
      S.dysenteriae infection regulates proinflammatory cytokines during intestinal
      inflammation is still obscure. In this study, we evaluated whether the
      interaction of beta-catenin and NF-kappaB regulates proinflammatory cytokines TNF
      alpha and IL-8 by modulating GSK-3beta activity during S.dysenteriae infection in
      rat ileal loop model. Here we demonstrated that S.dysenteriae infection stimulate
      beta-catenin degradation which in turn decreased the association between NF
      kappaB and beta-catenin. Also, we showed that S.dysenteriae infection increased
      GSK-3beta kinase activity which in turn phosphorylates beta-catenin for its
      degradation by ubiquitination and upregulates IL-8 through NF-kappaB activation
      thereby leading to inflammation. Thus these findings revealed the role of beta
      catenin/ NF-kappaB and GSK-3beta in modulating the inflammatory response during
      bacterial infection and also showed that beta-catenin acts as a critical
      regulator of inflammation.

PMID- 28430784
TI  - Non-invasive quantification of collagen turnover in renal transplant recipients.
AB  - Kidney allograft failure due to chronic injury/rejection remains the main cause
      of graft loss in renal transplant recipients (RTR). Here, we investigated whether
      specific biomarkers of extracellular matrix (ECM) turnover are associated with
      allograft function and chronic kidney disease (CKD) stage in RTR. Seventy-eight
      patients who attended the University Medical Center Groningen for a routine check
      up after kidney transplantation were enrolled in the study. Plasma and/or 24h
      urine samples were collected and specific matrix-metalloproteinase-generated neo
      epitope fragments of collagens were measured by enzyme-linked immunosorbent
      assay. Our results demonstrated that urinary levels of C3M, a marker for collagen
      type III degradation, correlated with estimated glomerular filtration rate (eGFR;
      r = 0.58, p<0.0001), with lower levels detected in the urine of patients with
      advanced CKD. In addition, plasma levels of Pro-C6, a marker for collagen type VI
      formation, significantly increased with disease progression and correlated with
      eGFR (r = -0.72, p<0.0001). Conversely, plasma C3M and urinary Pro-C6 levels
      showed no correlation with renal function. We identified two neo-epitope
      biomarkers of tissue turnover associated with ECM remodeling and fibrosis that
      can stratify patients by CKD stage. This is as promising first step towards non
      invasive monitoring of ECM turnover in the kidneys.

PMID- 28430785
TI  - Medical expulsive therapy for ureter stone using naftopidil: A multicenter,
      randomized, double-blind, and placebo-controlled trial.
AB  - OBJECTIVES: A prospective, multicenter, randomized, double-blind, placebo
      controlled trial evaluated the effects of naftopidil 75 mg for medical expulsive
      therapy for a single ureter stone. MATERIALS AND METHODS: Patients diagnosed with
      a ureter stone were prescribed aceclofenac 100 mg or a combined medication of
      tramadol 37.5 mg and acetaminophen 325 mg. Patients then randomly received either
      naftopidil 75 mg or placebo. Primary endpoint was the stone passage rate at 14
      days after medication. RESULTS: The 150 patients enrolled in 6 institutions
      randomly received either naftopidil (n = 75) or placebo (n = 75). The percentages
      of ureter stone passed spontaneously 14 days after medication was 60.9% in the
      naftopidil group and 53.3% in the placebo group. Stone-free rates and the total
      use of analgesics showed no significant differences between the two groups. Stone
      free rates at 14 days after medication were decreased when maximal stone size was
      increased: 39.4% (>= 5 mm), 15.5% (>= 6 mm), and 7.0% (>= 7 mm). CONCLUSIONS: The
      use of naftopidil 75 mg once daily was not effective in increasing spontaneous
      stone passage rates or reducing analgesic use. The maximal stone size < 6 mm and
      the follow-up for two weeks would be appropriate for applying medical expulsive
      therapy to patients with a single ureter stone.

PMID- 28430786
TI  - Repayment policy for multiple loans.
AB  - The Repayment Policy for Multiple Loans is about a given set of loans and a
      monthly incoming cash flow: what is the best way to allocate the monthly income
      to repay such loans? In this article, we close the almost 20-year-old open
      question about how to model the repayment policy for multiple loans problem
      together with its computational complexity. Thus, we propose a mixed integer
      linear programming model that establishes an optimal repayment schedule by
      minimizing the total amount of cash required to repay the loans. We prove that
      the most employed repayment strategies, such as the highest interest debt and the
      debt snowball methods, are not optimal. Experimental results on simulated cases
      based on real data show that our methodology obtains on average more than 4% of
      savings, that is, the debtor pays approximately 4% less to the bank or loaner,
      which is a considerable amount in finances. In certain cases, the debtor can save
      up to 40%.

PMID- 28430787
TI  - Feedback and efficient behavior.
AB  - Feedback is an effective tool for promoting efficient behavior: it enhances
      individuals' awareness of choice consequences in complex settings. Our study aims
      to isolate the mechanisms underlying the effects of feedback on achieving
      efficient behavior in a controlled environment. We design a laboratory experiment
      in which individuals are not aware of the consequences of different alternatives
      and, thus, cannot easily identify the efficient ones. We introduce feedback as a
      mechanism to enhance the awareness of consequences and to stimulate exploration
      and search for efficient alternatives. We assess the efficacy of three different
      types of intervention: provision of social information, manipulation of the
      frequency, and framing of feedback. We find that feedback is most effective when
      it is framed in terms of losses, that it reduces efficiency when it includes
      information about inefficient peers' behavior, and that a lower frequency of
      feedback does not disrupt efficiency. By quantifying the effect of different
      types of feedback, our study suggests useful insights for policymakers.

PMID- 28430788
TI  - Time and spatial trends in lymphoid leukemia and lymphoma incidence and survival
      among children and adolescents in Manitoba, Canada: 1984-2013.
AB  - OBJECTIVES: To test for time and spatial trends in lymphoid malignancies,
      including lymphoid leukemia (LL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma
      (NHL), in children and adolescents in the province of Manitoba, Canada. METHODS:
      Incident cases diagnosed between 1984 and 2013 were identified from the Manitoba
      Cancer Registry. We assessed time trends in age-standardized incidence rates
      using joinpoint regression and in 5-year relative survival using Poisson
      regression model. Kulldorff's scan method was used to assess spatial variation
      and clustering. RESULTS: Age-standardized incidence rates (per million person
      years) in males and females were 34.0 (95% confidence interval [CI] 28.9-39.1)
      and 26.2 (95% CI 21.5-30.7) for LL, 10.5 (95% CI 7.7-13.3) and 12.5 (95% CI 9.4
      15.7) for HL, 12.5 (95% CI 9.3-15.4) and 7.7 (95% CI 5.2-10.2) for NHL (except
      for Burkitt lymphomas), and 3.2 (95% CI 1.6-4.7) and 1.5 (95% CI 0.4-2.5) for
      Burkitt lymphomas. Age- and sex- standardized LL incidence rate increased 1.4%
      (95% CI 0.3%-2.5%) per year, while the changes for HL and NHL incidence rates
      were not statistically significant. There were geographic differences in age
      standardized incidence rates for LL, HL, and NHL and spatial clusters were
      detected in southern part of the province. Five-year relative survival has
      improved over time and there was no difference between rural and urban areas.
      CONCLUSIONS: Lymphoid leukemia incidence rate increased over time and varied by
      geographic area. Further research should examine the factors contributing to
      these trends.

PMID- 28430789
TI  - MiR-9-3p augments apoptosis induced by H2O2 through down regulation of Herpud1 in
      glioma.
AB  - MicroRNAs are short, single-stranded non-coding RNA molecules that function as
      regulators of tumor progression in various cancers, including glioma. The present
      study sought to investigate the biological functions of miR-9-3p in glioma
      progression. The results of a microRNA microarray indicated that microRNA-9-3p
      (miR-9-3p, miR-9*) is down-regulated in high-grade (grades III and IV) gliomas
      compared with non-tumor tissues. These results were confirmed with real-time PCR.
      The miR-9-3p expression level was associated with age and tumor grade. Herpud1
      was regulated by miR-9-3p in glioma cells and tissues and was identified as a miR
      9-3p target with luciferase reporter assays. Glioma cells transfected with miR-9
      3p mimics or HERPUD1-RNAi had more apoptotic cells than them in control after
      induced by H2O2. Our results indicated that low expression of miR-9-3p results in
      a high level of Herpud1, which may protect against apoptosis in glioma.

PMID- 28430790
TI  - Whole-genome sequencing suggests mechanisms for 22q11.2 deletion-associated
      Parkinson's disease.
AB  - OBJECTIVES: To investigate disease risk mechanisms of early-onset Parkinson's
      disease (PD) associated with the recurrent 22q11.2 deletion, a genetic risk
      factor for early-onset PD. METHODS: In a proof-of-principle study, we used whole
      genome sequencing (WGS) to investigate sequence variants in nine adults with
      22q11.2DS, three with neuropathologically confirmed early-onset PD and six
      without PD. Adopting an approach used recently to study schizophrenia in
      22q11.2DS, here we tested candidate gene-sets relevant to PD. RESULTS: No
      mutations common to the cases with PD were found in the intact 22q11.2 region.
      While all were negative for rare mutations in a gene-set comprising PD disease
      causing and risk genes, another candidate gene-set of 1000 genes functionally
      relevant to PD presented a nominally significant (P = 0.03) enrichment of rare
      putatively damaging missense variants in the PD cases. Polygenic score results,
      based on common variants associated with PD risk, were non-significantly greater
      in those with PD. CONCLUSIONS: The results of this first-ever pilot study of WGS
      in PD suggest that the cumulative burden of genome-wide sequence variants may
      contribute to expression of early-onset PD in the presence of threshold-lowering
      dosage effects of a 22q11.2 deletion. We found no evidence that expression of PD
      in 22q11.2DS is mediated by a recessive locus on the intact 22q11.2 chromosome or
      mutations in known PD genes. These findings offer initial evidence of the
      potential effects of multiple within-individual rare variants on the expression
      of PD and the utility of next generation sequencing for studying the etiology of
      PD.

PMID- 28430791
TI  - The medically managed patient with severe symptomatic aortic stenosis in the TAVR
      era: Patient characteristics, reasons for medical management, and quality of
      shared decision making at heart valve treatment centers.
AB  - BACKGROUND: Little is known about patients with severe symptomatic aortic
      stenosis (AS) who receive medical management despite evaluation at a heart valve
      treatment center. OBJECTIVE: We identified patient characteristics associated
      with medical management, physician-reported reasons for selecting medical
      management, and patients' perceptions of their involvement and satisfaction with
      treatment selection. METHODS AND RESULTS: Of 454 patients evaluated for AS at 9
      established heart valve treatment centers from December 12, 2013 to August 19,
      2014, we included 407 with severe symptomatic AS. Information was collected using
      medical record review and survey of patients and treating physicians. Of 407
      patients, 212 received transcatheter aortic valve replacement (TAVR), 124
      received surgical aortic valve replacement (SAVR), and 71 received medical
      management (no SAVR/TAVR). Thirty-day predicted mortality was higher in patients
      receiving TAVR (8.7%) or medical management (9.8%) compared with SAVR (3.4%)
      (P<0.001). Physician-reported reasons for medical management included patient
      preference (31.0%), medical futility (19.7%), inoperability/anatomic
      infeasibility (11.3%), and inadequate vascular access (8.5%). Compared with
      patients receiving AVR, medically managed patients were less likely to report
      that they received enough information about the pros and cons of treatment
      options (P = 0.03), that their physicians involved them in treatment decisions
      (P<0.001), and that final decisions were the right ones (P<0.001). CONCLUSIONS:
      Patient preference was the most common physician-reported reason for selecting
      non-invasive AS management, yet patients not undergoing AVR after valve center
      evaluation reported being less likely to receive sufficient education about
      treatment options and more likely to feel uncertain about final treatment
      decisions. Greater attention to shared decision making may improve the experience
      of care for this vulnerable group of patients.

PMID- 28430792
TI  - The influence of sagittal profile alteration and final lordosis on the clinical
      outcome of cervical spondylotic myelopathy. A Delta-Omega-analysis.
AB  - PURPOSE: Decompression and maintaining or restoring a cervical lordosis are major
      goals in the surgical treatment of cervical spondylotic myelopathy (CSM).
      Numerous studies support the assumption that cervical lordosis is a key factor
      for neurological recovery and pain reduction. However, even kyphotic patients can
      be asymptomatic. The balance of the spine is subject of an increasing number of
      publications. The main purpose of the study was to evaluate the validity of
      lordotic alignment on the course of CSM and to set this parameter in context with
      well-validated tools, namely the modified Japanese Orthopaedic Association
      scoring system (mJOAS) and the visual analogue scale (VAS), to predict and
      measure the clinical outcome after surgery. METHODS: This is a retrospective
      study with prospectively collected data of a heterogeneous cohort. The authors
      analyzed the records of 102 patients suffering from CSM that underwent
      decompressive surgery and instrumentation. Clinical outcome was assessed by using
      the mJOAS, VAS and Odom's criteria. The radiological analysis involved comparison
      of pre- and postoperative radiographs. The patients were divided into subgroups
      to be able to compare the influence of various amounts of correction (3 Delta
      groups: <0 degrees , 1-7 degrees  and >=8 degrees ) and final lordosis (4 Omega
      groups: 0-7 degrees , 8-14 degrees , 15-21 degrees , >=22 degrees ). RESULTS: 219
      levels were fused in 102 patients. Surgery improved the clinical outcome of all
      groups significantly. A lordotic profile was achieved in all analyzed groups.
      Patients that showed small lordosis after surgery (<8 degrees ) did not have an
      inferior clinical outcome compared to patients with larger cervical lordosis (>14
      degrees ). The comparison of Odom's criteria showed that preoperatively kyphotic
      patients benefitted more from surgery than lordotic patients (p = 0.029), but no
      differences could be seen comparing neck pain and neurological improvement. The
      improvement of pain and neurological impairment measured by VAS and mJOAS
      supports the statistical impact and validity of the data despite comparatively
      small numbers of patients. The lack of postoperative kyphosis is a major
      limitation of the study to encompass the impact of sagittal alignment on clinical
      outcome. CONCLUSIONS: Decompression and stabilization appear to be key elements
      of surgical treatment of CSM. While the achievement of cervical lordosis remains
      a major goal of surgery, clinical improvement is not hindered in patients who
      show small lordosis. However, kyphosis should be eliminated in symptomatic
      patients. The terms "balance" and "physiologic lordosis" remain complex entities
      without clear definition. To check the results of our study controlled randomized
      trials to validate and determine the exact role of cervical balance on the course
      of CSM would be helpful.

PMID- 28430793
TI  - Identifying a combined construct of grief and explosive anger as a response to
      injustice amongst survivors of mass conflict: A latent class analysis of data
      from Timor-Leste.
AB  - Previous studies have identified high rates of explosive anger amongst post
      conflict populations including Timor-Leste. We sought to test whether explosive
      anger was integrally associated with symptoms of grief amongst the Timorese, a
      society that has experienced extensive conflict-related losses. In 2010 and 2011
      we recruited adults (n = 2964), 18-years and older, living in an urban and a
      rural village in Timor-Leste. We applied latent class analysis to identify
      subpopulations based on symptoms of explosive anger and grief. The best fitting
      model comprised three classes: grief (24%), grief-anger (25%), and a low symptom
      group (51%). There were more women and urban dwellers in the grief and grief
      anger classes compared to the reference class. Persons in the grief and grief
      anger classes experienced higher rates of witnessing murder and atrocities and
      traumatic losses, ongoing poverty, and preoccupations with injustice for the two
      historical periods of conflict (the Indonesian occupation and the later internal
      conflict). Compared to the reference class, only the grief-anger class reported
      greater exposure to extreme deprivations during the conflict, ongoing family
      conflict, and preoccupations with injustice for contemporary times; and compared
      to the grief class, greater exposure to traumatic losses, poverty, family
      conflict and preoccupations with injustice for both the internal conflict and
      contemporary times. A substantial number of adults in this post-conflict country
      experienced a combined constellation of grief and explosive anger associated with
      extensive traumatic losses, deprivations, and preoccupations with injustice.
      Importantly, grief-anger may be linked to family conflict in this post-conflict
      environment.

PMID- 28430794
TI  - Experimental demonstration of a trophic cascade in the Galapagos rocky subtidal:
      Effects of consumer identity and behavior.
AB  - In diverse tropical webs, trophic cascades are presumed to be rare, as species
      interactions may dampen top-down control and reduce their prevalence. To test
      this hypothesis, we used an open experimental design in the Galapagos rocky
      subtidal that enabled a diverse guild of fish species, in the presence of each
      other and top predators (sea lions and sharks), to attack two species of sea
      urchins grazing on benthic algae. Time-lapse photography of experiments on
      natural and experimental substrates revealed strong species identity effects:
      only two predator species-blunthead triggerfish (Pseudobalistes naufragium) and
      finescale triggerfish (Balistes polylepis)-drove a diurnal trophic cascade
      extending to algae, and they preferred large pencil urchins (Eucidaris
      galapagensis) over green urchins (Lytechinus semituberculatus). Triggerfish
      predation effects were strong, causing a 24-fold reduction of pencil urchin
      densities during the initial 21 hours of a trophic cascade experiment. A trophic
      cascade was demonstrated for pencil urchins, but not for green urchins, by
      significantly higher percent cover of urchin-grazed algae in cages that excluded
      predatory fish than in predator access (fence) treatments. Pencil urchins were
      more abundant at night when triggerfish were absent, suggesting that this species
      persists by exploiting a nocturnal predation refuge. Time-series of pencil urchin
      survivorship further demonstrated per capita interference effects of hogfish and
      top predators. These interference effects respectively weakened and extended the
      trophic cascade to a fourth trophic level through behavioral modifications of the
      triggerfish-urchin interaction. We conclude that interference behaviors capable
      of modifying interaction strength warrant greater attention as mechanisms for
      altering top-down control, particularly in speciose food webs.

PMID- 28430795
TI  - IgM antibodies to oxidized phosphatidylserine as protection markers in
      cardiovascular disease among 60-year olds.
AB  - OBJECTIVE: Phosphatidylserine is exposed on apoptotic cells and is prone to
      oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS
      (anti-OxPS) with the risk of cardiovascular disease (CVD). METHODS: Among sixty
      year olds from Stockholm County in Sweden, previously screened for cardiovascular
      risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified
      during a 5-year follow-up. Using a nested case-control design, 622 age- and sex
      matched controls were selected. Odds ratios (OR) with 95% intervals (CI) were
      calculated by conditional logistic regression. IgM anti-OxPS was measured by
      ELISA. Phagocytosis of apoptotic Jurkat-cells by macrophages was studied by flow
      cytometry. RESULTS: Anti-OxPS levels were lower among cases (median
      (interquartile range): 80.7 (60.9-101.0 vs. 84.6 (65.8-109.6); p = 0.047); among
      men (76.6 (55.8-99.2) vs. 82.0 (63.1-105.1); p = 0.022) and among women 89.6
      (72.3-110.1) vs. 89.8 (69.9-114.4); p = 0.79). After adjustment for smoking, BMI,
      diabetes mellitus type II, hypercholesterolaemia and hypertension, and dividing
      into quartiles, using the highest quartile (quartile 4) as reference, quartile 3
      was associated with a OR of 1.74 (CI 1.08-2.81). Quartiles 2 and 1 had similar
      associations, the later reaching statistical significance. Among men associations
      were stronger whereas no significant associations were observed in women. The OR
      of MI/angina comparing quartile 3 with quartile 4 was 2.31 (CI 1.30-4.11). The OR
      for quartile 2 and 1, respectively, were similar as for quartile 3. Total IgM
      increased uptake of apoptotic cells, which was reversed if incubated with OxPS.
      CONCLUSIONS: IgM anti-OxPS is a novel potential protection marker for CVD, in
      particular in men. Increased phagocytosis of dying/dead cells could be one
      potential underlying mechanism.

PMID- 28430796
TI  - Prevalence and associated factors of tuberculosis and diabetes mellitus
      comorbidity: A systematic review.
AB  - INTRODUCTION: The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has
      become a major global public health concern. There is mounting evidence from
      different countries on the burden of TB and DM comorbidity. The objective of this
      systematic review was to summarize the existing evidence on prevalence and
      associated/risk factors of TBDM comorbidity at global and regional levels.
      METHODS: Ovid Medline, Embase, Global health, Cochrane library, Web of science
      and Scopus Elsevier databases were searched to identify eligible articles for the
      systematic review. Data were extracted using standardized excel form and pilot
      tested. Median with interquartile range (IQR) was used to estimate prevalence of
      TBDM comorbidity. Associated/risk factors that were identified from individual
      studies were thematically analyzed and described. RESULTS: The prevalence of DM
      among TB patients ranged from 1.9% to 45%. The overall median global prevalence
      was 16% (IQR 9.0%-25.3%) Similarly, the prevalence of TB among DM patients ranged
      from 0.38% to 14% and the overall median global prevalence was 4.1% (IQR 1.8%
      6.2%). The highest prevalence of DM among TB patients is observed in the studied
      countries of Asia, North America and Oceania. On the contrary, the prevalence of
      TB among DM patients is low globally, but relatively higher in the studied
      countries of Asia and the African continents. Sex, older age, urban residence,
      tobacco smoking, sedentary lifestyle, poor glycemic control, having family
      history of DM and TB illness were among the variables identified as
      associated/risk factors for TBDM comorbidity. CONCLUSION: This systematic review
      revealed that there is a high burden of DM among TB patients at global level. On
      the contrary, the global prevalence of TB among DM patients is low. Assessing the
      magnitude and risk/associated factors of TBDM comorbidity at country/local level
      is crucial before making decisions to undertake TBDM integrated services.

PMID- 28430797
TI  - Effect of quinoline based 1,2,3-triazole and its structural analogues on growth
      and virulence attributes of Candida albicans.
AB  - Candida albicans, along with some other non-albicans Candida species, is a group
      of yeast, which causes serious infections in humans that can be both systemic and
      superficial. Despite the fact that extensive efforts have been put into the
      discovery of novel antifungal agents, the frequency of these fungal infections
      has increased drastically worldwide. In our quest for the discovery of novel
      antifungal compounds, we had previously synthesized and screened quinoline
      containing 1,2,3-triazole (3a) as a potent Candida spp inhibitor. In the present
      study, two structural analogues of 3a (3b and 3c) have been synthesized to
      determine the role of quinoline and their anti-Candida activities have been
      evaluated. Preliminary results helped us to determine 3a and 3b as lead
      inhibitors. The IC50 values of compound 3a for C. albicans ATCC 90028 (standard)
      and C. albicans (fluconazole resistant) strains were 0.044 and 2.3 MUg/ml,
      respectively while compound 3b gave 25.4 and 32.8 MUg/ml values for the same
      strains. Disk diffusion, growth and time kill curve assays showed significant
      inhibition of C. albicans in the presence of compounds 3a and 3b. Moreover, 3a
      showed fungicidal nature while 3b was fungistatic. Both the test compounds
      significantly lower the secretion of proteinases and phospholipases. While, 3a
      inhibited proteinase secretion in C. albicans (resistant strain) by 45%, 3b
      reduced phospholipase secretion by 68% in C. albicans ATCC90028 at their
      respective MIC values. Proton extrusion and intracellular pH measurement studies
      suggested that both compounds potentially inhibit the activity of H+ ATPase, a
      membrane protein that is crucial for various cell functions. Similarly, 95-97%
      reduction in ergosterol content was measured in the presence of the test
      compounds at MIC and MIC/2. The study led to identification of two quinoline
      based potent inhibitors of C. albicans for further structural optimization and
      pharmacological investigation.

PMID- 28430798
TI  - Evaluation of mature soybean pods as a food source for two pod-sucking bugs,
      Riptortus pedestris (Hemiptera: Alydidae) and Halyomorpha halys (Hemiptera:
      Pentatomidae).
AB  - Riptortus pedestris (Fabricius) and Halyomorpha halys (Stal) cause injury to
      soybeans by piercing and sucking pods and seeds. Growers believe that new damage
      decreases near to harvest despite the occurrence of these bugs at that time. As
      this question has never been assessed, we evaluated two diets: a) mature soybean
      pods (dried shell + dried soybean seeds) and b) dried soybean seeds for the two
      bugs by assessing their biological, behavioral, and morphological attributes on
      each diet in laboratory. While nymphs of both species were able to develop and
      adults able to reproduce on the tested diets, bugs fed on pods had longer
      development times and 2.2 to 5.0 times higher mortality rates than bugs fed on
      seeds. Furthermore, adult longevity of R. pedestris and H. halys fed on pods was
      8.4 and 7.5 days shorter, respectively, than that of bugs fed on seeds. However,
      pod feeding had no effect on adult fecundity or egg viability. In a behavioral
      choice test, adult R. pedestris preferred seeds over pods and probed seeds longer
      than pods. On average, adult H. halys also preferred seeds over pods, although
      15.6% of H. halys showed the reverse, preferring pods over seeds. The proboscis
      length and estimated depth of stylet penetration into the host tissue of both
      nymphs and adults of both species was much greater than the thickness of the pod
      shell, suggesting that mouthpart structure does not explain the negative effects
      of pods vs. seeds. In conclusion, mature soybean pods were found to be a suitable
      food source for both R. pedestris and H. halys despite some negative effects, and
      thus careful attention should be paid to the population levels of these two bugs
      approaching harvest to reduce economic damage in soybean.

PMID- 28430799
TI  - Diagnostic and prognostic value of long noncoding RNAs as biomarkers in
      urothelial carcinoma.
AB  - Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to
      oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to
      be overexpressed and proposed as biomarkers. As most reports have not been
      confirmed independently in large tissue sets, we aimed to validate the diagnostic
      and prognostic value of lncRNA upregulation in independent cohorts of UC
      patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1,
      MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and
      correlated to clinicopathological parameters including follow-up data (set 1: N n
      = 10; T n = 106). Additionally, publicly available TCGA data was investigated for
      differential expression in UC tissues (set 2: N n = 19; T n = 252,) and
      correlation to overall survival (OS). All proposed candidates tended to be
      upregulated in tumour tissues, with the exception of MALAT1, which was rather
      diminished in cancer tissues of both data sets. However, strong overexpression
      was generally limited to individual tumour tissues and statistically significant
      overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue
      set 2, but for no candidate in set 1. Altered expression of individual lncRNAs
      was associated with overall survival, but not consistently between both patient
      cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with
      muscle-invasive tumours was significantly correlated with worse OS in both
      cohorts. Further analysis revealed that tumours with low TUG1 expression are
      characterized by a basal-squamous-like subtype signature accounting for the
      association with poor outcome. In conclusion, our study demonstrates that
      overexpression of the candidate lncRNAs is found in many UC cases, but does not
      occur consistently and strongly enough to provide reliable diagnostic or
      prognostic value as an individual biomarker. Subtype-dependent expression
      patterns of lncRNAs like TUG1 could become useful to stratify patients by
      molecular subtype, thus aiding personalized treatments.

PMID- 28430801
TI  - Honey bees preferentially consume freshly-stored pollen.
AB  - Honey bees (Apis mellifera) collect and store both honey and pollen in preserved
      forms. Pollen storage involves the addition of honey or nectar and oral
      secretions to pollen granules. It is controversial whether the duration of pollen
      storage alters the palatability or nutritive value of the pollen storage medium.
      We examined how bees utilize different-aged stored pollen during an extended
      pollen flow. The deposition of pollen into wax cells and subsequent consumption
      were monitored daily on 18 brood frames from 6 colonies over an 8d observation
      period. Despite a greater abundance of older stored pollen cells on brood frames,
      bees showed a marked preference for the consumption of freshly-stored pollen. Two
      to four day-old pollen cell contents were significantly more likely to be
      consumed, while pollen cell contents more than seven days old were eaten at much
      lower rates. Similar experiments that controlled for cell abundance and spatial
      effects using cage assays yielded the same result. One day-old stored pollen was
      consumed approximately three times more often than 10d-old stored pollen, and two
      times more often than 5d-old stored pollen. These consumption preferences for
      freshly-stored pollen occurred despite a lack of clear developmental advantages.
      Young adult workers reared for 7 days on 1d-, 5d-, or 10d-old stored pollen
      showed no difference in body mass, stored pollen consumption, hindgut fecal
      material accumulation, or hypopharyngeal gland (HPG) protein titers, suggesting
      that different-aged pollen stores did not vary in their nutritional value to
      adult bees. These findings are inconsistent with the hypothesis promoting a
      period of microbially-mediated, "beebread maturation" that results in greater
      palatability or nutritive value for aged pollen stores. Rather, stored pollen
      that is not eaten in the first few days accumulates as excess stores preserved in
      a less preferred, but nutritionally-similar state.

PMID- 28430802
TI  - The quality changes in fresh frozen plasma of the blood donors at high altitude.
AB  - OBJECTIVE: According to the international guidelines, fresh frozen plasma (FFP)
      is unanimously used to treat coagulation disorders. The quality of FFP is
      critical for the clinical transfusion. Till now, few studies have integratedly
      evaluated the differences of FFP from blood donors at between high altitude (HA)
      and low altitude (LA). Besides, there were no special quality standards for HA
      FFP in China. MATERIALS AND METHODS: Up to 41 HA (Lhasa, 3700 m) and 46 LA
      (Chengdu, 500 m) blood donors were included in our study to estimate the
      differences of FFP from HA and LA blood donors. The concentration of total plasma
      proteins, prothrombin time (PT), activated partial thromboplastin time (aPTT),
      thrombin time (TT), fibrinogen (Fbg), factor (F) II, FV, FVII, FVIII, FIX, FX,
      FXI, FXII, D-dimer, protein C (PC), protein S (PS), antithrombin III (ATIII) and
      von Willebrand factor antigen (vWF:Ag) were determined, respectively. RESULTS: As
      compared with FFP of LA blood donors, the total protein content of HA blood
      donors showed a significant decrease (65.2+/-8.9 vs.57.2+/-6.3 g/L; p<0.001); PT,
      aPTT, TT were significantly increased (p<0.001); the levels of FII, FV, FVII,
      FVIII, FIX, FX, FXI, FXII and vWF:Ag were notably decreased (all p<0.05), whereas
      Fbg and D-dimer were dramaticly increased (p = 0.038). Additionly, in HA blood
      donors, vWF: Ag and FVIII:C of O-group was significantly lower (p<0.05) than that
      of non-O-group. It should be noted that FVIII:C of HA blood donors (0.64+/-0.10
      IU/mL) was lower than the current Chinese quality requirements for FFP (>= 0.7
      IU/ml). No significant differences were observed in PC, PS and ATIII. CONCLUSION:
      In general, our findings showed that the quality of FFP was significantly
      different between HA and LA blood donors, and the current Chinese quality
      requirements of FFP are not suitable for HA FFP. Therefore, setting up a special
      quality requirement for HA is quite necessary and meaningful.

PMID- 28430800
TI  - The burden of trisomy 21 disrupts the proteostasis network in Down syndrome.
AB  - Down syndrome (DS) is a genetic disorder caused by trisomy of chromosome 21.
      Abnormalities in chromosome number have the potential to lead to disruption of
      the proteostasis network (PN) and accumulation of misfolded proteins. DS
      individuals suffer from several comorbidities, and we hypothesized that
      disruption of proteostasis could contribute to the observed pathology and
      decreased cell viability in DS. Our results confirm the presence of a disrupted
      PN in DS, as several of its elements, including the unfolded protein response,
      chaperone system, and proteasomal degradation exhibited significant alterations
      compared to euploid controls in both cell and mouse models. Additionally, when
      cell models were treated with compounds that promote disrupted proteostasis, we
      observed diminished levels of cell viability in DS compared to controls.
      Collectively our findings provide a cellular-level characterization of PN
      dysfunction in DS and an improved understanding of the potential pathogenic
      mechanisms contributing to disrupted cellular physiology in DS. Lastly, this
      study highlights the future potential of designing therapeutic strategies that
      mitigate protein quality control dysfunction.

PMID- 28430803
TI  - Increase in serum albumin concentration is associated with prediabetes
      development and progression to overt diabetes independently of metabolic
      syndrome.
AB  - AIM: Serum albumin concentration is associated with both type 2 diabetes and
      metabolic syndrome (MetS). We sought to investigate whether baseline serum
      albumin and change in serum albumin could be independent risk factors for
      prediabetes in subjects without MetS. We further examined the effect of serum
      albumin on progression to overt diabetes in subjects who developed prediabetes.
      METHODS: Among 10,792 participants without diabetes and MetS who consecutively
      underwent yearly health check-ups over six years, 9,807 subjects without incident
      MetS were enrolled in this longitudinal retrospective study. The risk of
      developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed
      according to baseline and percent change in serum albumin concentration using Cox
      regression analysis. Serial changes in serum albumin concentration were measured
      from baseline to one year before prediabetes diagnosis, and then from the time of
      prediabetes diagnosis to progression to overt diabetes or final follow-up.
      RESULTS: A total of 4,398 incident cases of prediabetes developed during 35,807
      person-years (median 3.8 years). The hazard ratio for incident prediabetes
      decreased as percent change in serum albumin concentration (quartiles and per 1%)
      increased in a crude and fully adjusted model. However, baseline serum albumin
      concentration itself was not associated with prediabetic risk. Serum albumin
      levels kept increasing until the end of follow-up in prediabetic subjects who
      returned to normal glycemic status, whereas these measures did not change in
      prediabetic subjects who developed type 2 diabetes. Serum albumin concentration
      measured at the end of follow-up was the highest in the regression group,
      compared to the stationary (p = 0.014) or progression groups (p = 0.009).
      CONCLUSIONS: Increase in serum albumin concentration might protect against early
      glycemic deterioration and progression to type 2 diabetes even in subjects
      without MetS.

PMID- 28430804
TI  - Risk stratification for venous thromboembolism in patients with testicular germ
      cell tumors.
AB  - BACKGROUND: Patients with testicular germ cell tumors (TGCT) have an increased
      risk for venous thromboembolism (VTE). We identified risk factors for VTE in this
      patient cohort and developed a clinical risk model. METHODS: In this
      retrospective cohort study at the Medical University of Graz we included 657
      consecutive TGCT patients across all clinical stages. A predictive model for VTE
      was developed and externally validated in 349 TGCT patients treated at the
      University Hospital Zurich. RESULTS: Venous thromboembolic events occurred in 34
      (5.2%) patients in the Graz cohort. In univariable competing risk analysis,
      higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the
      strongest predictors of VTE (p<0.0001). As the presence of a RPLN with more than
      5cm in greatest dimension without coexisting visceral metastases is classified as
      cS IIC, we constructed an empirical VTE risk model with the following four
      categories (12-month-cumulative incidence): cS IA-B 8/463 patients (1.7%), cS IS
      IIB 5/86 patients (5.9%), cS IIC 3/21 patients (14.3%) and cS IIIA-C 15/70
      patients (21.4%). This risk model was externally validated in the Zurich cohort
      (12-month-cumulative incidence): cS IA-B (0.5%), cS IS-IIB (6.0%), cS IIC (11.1%)
      and cS IIIA-C (19.1%). Our model had a significantly higher discriminatory
      performance than a previously published classifier (RPLN-VTE-risk-classifier)
      which is based on the size of RPLN alone (AUC-ROC: 0.75 vs. 0.63, p = 0.007).
      CONCLUSIONS: According to our risk stratification, TGCT patients with cS IIC and
      cS III disease have a very high risk of VTE and may benefit from primary
      thromboprophylaxis for the duration of chemotherapy.

PMID- 28430805
TI  - Effect of the glucocorticoid receptor antagonist RU486 on MK-801 induced
      behavioural sensitisation.
AB  - Stress is known to modulate sensitisation to repeated psychostimulant exposure.
      However, there is no direct evidence linking glucocorticoids and sensitisation
      achieved by repeated administration of the NMDA receptor antagonist MK-801. We
      tested the hypothesis that co-administration of RU486, a glucocorticoid receptor
      (GR) antagonist, prior to repeated daily MK-801 injections would block the
      expression of locomotor sensitisation due to its dual effects on corticosterone
      and dopamine. We employed a repeated MK-801 administration locomotor
      sensitisation paradigm in male Sprague Dawley rats. RU486 or a dimethyl sulfoxide
      (DMSO) vehicle was co-administered with MK-801 or saline during the induction
      phase. Subsequent to withdrawal, rats were challenged with MK-801 alone to test
      for the expression of sensitisation. In a separate cohort of rats, plasma
      corticosterone levels were quantified from blood samples taken on the 1st, 4th
      and 7th day of induction and at expression. One day after challenge, nucleus
      accumbens tissue levels of dopamine and its metabolites DOPAC and HVA were
      measured. During the induction phase, RU486 progressively enhanced locomotor
      sensitisation to MK-801. RU486 and MK-801 both showed stimulatory effects on
      corticosterone levels and this was further augmented when given in combination.
      Contrary to our hypothesis, RU486 did not block the expression of locomotor
      sensitisation to MK-801 and actually increased levels of dopamine, DOPAC and HVA
      in nucleus accumbens tissue. Our results showed that RU486 has augmentative
      rather than inhibitory effects on MK-801-induced sensitisation. This study
      indicates a divergent role for glucocorticoids in sensitisation to MK-801
      compared to sensitisation with other psychostimulants.

PMID- 28430806
TI  - Incidence and risk factors for post-penetrating keratoplasty glaucoma: A
      systematic review and meta-analysis.
AB  - OBJECTIVES: To establish the incidence and risk factors for post penetrating
      keratoplasty glaucoma (PKKG). METHODS: Studies published between 1947 and 2016
      regarding penetrating keratoplasty (PK) were identified using an electronic
      search and reviewed. For search purpose, PKKG was defined as ocular hypertension
      (> 21mmHg) after PK. The incidence and risk factors of PKKG were extracted for
      all studies. Pooled incidence, odd ratios (ORs) and 95% confidence intervals
      (CIs) were calculated. RESULTS: Thirty studies reporting on 27146 patients were
      included in the analysis of the incidence and risk factors for PKKG. Exact PKKG
      definitions used in the literature could be classified in to three subgroups: I,
      ocular hypertension (> 21mmHg) after PK; II, I plus > 4 weeks medical treatment
      required; III, II plus treatment escalation among patients with preexisting
      glaucoma. Overall (Definition I) pooled incidence in all studies was 21.5% (95%
      CI 17.8%, 25.7%). The incidence varied according to different definitions. The
      highest incidence value was found when only studies using Goldmann tonometer were
      included (22.5%), while the lowest incidence was found when a strict definition
      was used and steroid-induced PPKG was excluded (12.1%). The incidence was higher
      in patients with preexisting glaucoma, bullous keratopathy (BK), aphakia,
      pseudophakia, failed graft, and surgical indication of trauma. A triple procedure
      (combined PK with extra capsular cataract extraction and intraocular lens
      implantation) was not identified as being associated with the increased risk for
      PKKG. CONCLUSIONS: The overall pooled incidence of PKKG was 21.5%, but it varied
      according to the criteria used to define the presence of PPKG. Strong risk
      factors for PKKG included preexisting glaucoma and aphakia, while modest
      predictors included pseudophakia, regrafting, and preoperative diagnosis like BK
      and trauma. There may not be sufficient evidence to identify a significant
      association between a triple procedure and PKKG.

PMID- 28430807
TI  - Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF.
AB  - BACKGROUND: Diagnosis of pulmonary (PTB) and extra-pulmonary tuberculosis (EPTB)
      in smear-negative patients can be difficult. We assessed retrospectively the
      performance of Xpert MTB/RIF system (Xpert, Cepheid) in diagnosing smear-negative
      tuberculosis (TB), which represents the most common form of TB in a low incidence
      setting. METHODS: Performance of Xpert was compared to acid-fast microscopic
      examination using Ziehl-Neelsen (ZN) stain in patients with culture-confirmed TB.
      RESULTS: 386 Mycobacterium tuberculosis (MTB) culture-positive samples were
      detected out of 5170 specimens tested with smear microscopy, Xpert and culture:
      323 were both culture- and Xpert-positive, and 63 culture-positive only. Of
      these, 234 (60.6%) were smear-negative. In addition Xpert detected 40 probable TB
      cases, based on clinical findings, which were culture-negative. Compared to
      culture, Xpert showed an overall sensitivity of 83.7% and a specificity of 99.1%;
      sensitivity was higher for respiratory samples (86.5%) than for non-respiratory
      samples (76.8%). Xpert sensitivity for smear-negative culture-confirmed TB was
      73.1% and was not influenced by TB localization. As sensitivity of microscopy
      alone was poor (39.4%), Xpert improved both diagnosis of pulmonary TB (Delta =
      36.5%) and extra-pulmonary TB (Delta = 63.4%). CONCLUSIONS: Xpert MTB/RIF is a
      sensitive method for rapid diagnosis of TB compared to the conventional ZN
      staining. Xpert can serve as a sensitive and time-saving diagnostic method for
      microbiological diagnosis of smear-negative TB in countries with a low TB
      prevalence.

PMID- 28430809
TI  - Correction: Atheists and Agnostics Are More Reflective than Religious Believers:
      Four Empirical Studies and a Meta-Analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0153039.].

PMID- 28430808
TI  - Quantification of hypoxia-related gene expression as a potential approach for
      clinical outcome prediction in breast cancer.
AB  - Breast cancers are solid tumors frequently characterized by regions with low
      oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by
      "hypoxia inducible factors" that mediate transcriptional modifications involved
      in drug resistance and tumor progression leading to metastasis and relapse
      occurrence. In this study, we investigated the prognostic value of hypoxia
      related gene expression in breast cancer. A systematic review was conducted to
      select a set of 45 genes involved in hypoxia signaling pathways and breast tumor
      progression. Gene expression was quantified by RT-qPCR in a retrospective series
      of 32 patients with invasive ductal carcinoma. Data were analyzed in relation to
      classical clinicopathological criteria and relapse occurrence. Coordinated
      overexpression of selected genes was observed in high-grade and HER2+ tumors.
      Hierarchical cluster analysis of gene expression significantly segregated
      relapsed patients (p = 0.008, Chi2 test). All genes (except one) were up
      regulated and six markers were significantly expressed in tumors from recurrent
      patients. The expression of this 6-gene set was used to develop a basic algorithm
      for identifying recurrent patients according to a risk score of relapse. Analysis
      of Kaplan-Meier relapse-free survival curves allowed the definition of a
      threshold score of 2 (p = 0.021, Mantel-Haenszel test). The risk of recurrence
      was increased by 40% in patients with a high score. In addition to classical
      prognostic factors, we showed that hypoxic markers have potential prognostic
      value for outcome and late recurrence prediction, leading to improved treatment
      decision-making for patients with early-stage invasive breast cancer. It will be
      necessary to validate the clinical relevance of this prognostic approach through
      independent studies including larger prospective patient cohorts.

PMID- 28430810
TI  - Efficacy of fluoride varnishes for preventing enamel demineralization after
      interproximal enamel reduction. Qualitative and quantitative evaluation.
AB  - OBJECTIVES: To evaluate quantitatively and qualitatively the changes produced to
      enamel after interproximal reduction and subjected to demineralization cycles,
      after applying a fluoride varnish (Profluorid) and a fluoride varnish containing
      tricalcium phosphate modified by fumaric acid (Clinpro White). MATERIALS AND
      METHODS: 138 interproximal dental surfaces were divided into six groups: 1)
      Intact enamel; 2) Intact enamel + demineralization cycles (DC); 3) Interproximal
      Reduction (IR); 4) IR + DC; 5) IR + Profluorid + DC; 6) IR + Clinpro White + DC.
      IR was performed with a 0.5 mm cylindrical diamond bur. The weight percentage of
      calcium (Ca), phosphorous (P) and fluoride (F) were quantified by energy
      dispersive X-ray spectrometry (EDX). Samples were examined under scanning
      electron microscopy (SEM). RESULTS: The weight percentage of Ca was significantly
      higher (p<0.05) in Groups 1, 2 and 5 than Groups 4 and 6. No significant
      differences were detected in the weight percentage of Ca between Group 3 and the
      other groups (p>0.05). The weight percentage of P was similar among all six
      groups (p>0.05). F was detected on 65% of Group 6 surfaces. SEM images of Groups
      4 and 6 showed signs of demineralization, while Group 5 did not. CONCLUSIONS:
      Profluorid application acts as a barrier against the demineralization of
      interproximally reduced enamel.

PMID- 28430811
TI  - Antimicrobial resistance in coagulase-positive staphylococci isolated from
      companion animals in Australia: A one year study.
AB  - Methicillin-resistant coagulase-positive staphylococci (CoPS) have become
      increasingly recognised as opportunistic pathogens that limit therapeutic options
      in companion animals. The frequency of methicillin resistance amongst clinical
      isolates on an Australia-wide level is unknown. This study determined
      antimicrobial susceptibility patterns for CoPS isolated from clinical infections
      in companion animals (dogs, cats and horses) as part of the first nation-wide
      survey on antimicrobial resistance in animal pathogens in Australia for a one
      year period (January 2013 to January 2014). Clinical Staphylococcus spp. isolates
      (n = 888) obtained from 22 veterinary diagnostic laboratories were identified by
      MALDI-TOF mass spectrometry and subjected to antimicrobial susceptibility testing
      for 16 antimicrobials, representing 12 antimicrobial classes. Potential risk
      factors associated with methicillin resistance in Staphylococcus pseudintermedius
      isolates from dogs were analysed based on demographic factors and clinical
      history, including gender, age, previous antimicrobial treatment, chronic and/or
      recurrent diseases and site of infections. The most commonly identified CoPS were
      S. pseudintermedius (70.8%; dogs n = 616, cats n = 13) and S. aureus (13.2%,
      horses n = 53, dogs n = 47 and cats n = 17). Overall, the frequency of
      methicillin resistance among S. pseudintermedius (MRSP) and S. aureus (MRSA) was
      11.8% and 12.8%, respectively. MRSP isolates were strongly associated with
      resistance to fluoroquinolones (OR 287; 95%CI 91.2-1144.8) and clindamycin (OR
      105.2, 95%CI 48.5-231.9). MRSA isolates from dogs and cats were also more likely
      to be resistant to fluoroquinolones (OR 5.4, 95%CI 0.6-252.1), whereas MRSA from
      horses were more likely to be resistant to rifampicin. In multivariate analysis,
      MRSP-positive status was significantly associated with particular infection
      sites, including surgical (OR 8.8; 95%CI 3.74-20.7), and skin and soft tissue (OR
      3.9; 95%CI 1.97-7.51). S. pseudintermedius isolated from dogs with surgical site
      infections were three times more likely to be methicillin-resistant if cases had
      received prior antimicrobial treatment. Whilst the survey results indicate the
      proportion of CoPS obtained from Australian companion animals that are
      methicillin-resistant is currently moderate, the identified risk factors suggest
      that it could rapidly increase without adequate biosecurity and infection control
      procedures in veterinary practice.

PMID- 28430812
TI  - NaCl cotransporter abundance in urinary vesicles is increased by calcineurin
      inhibitors and predicts thiazide sensitivity.
AB  - Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and
      tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common
      side effect of CNIs is hypertension. Renal salt transporters such as NCC are
      excreted in urinary extracellular vesicles (uEVs) after internalization into
      multivesicular bodies. Human studies indicate that CNIs also increase NCC
      abundance in uEVs, but results are conflicting and no relationship with NCC
      function has been shown. Therefore, we investigated the effects of CsA and Tac on
      the abundance of both total NCC (tNCC) and phosphorylated NCC at Thr60
      phosphorylation site (pNCC) in uEVs, and assessed whether NCC abundance in uEVs
      predicts the blood pressure response to thiazide diuretics. Our results show that
      in kidney transplant recipients treated with cyclosporine (n = 9) or tacrolimus
      (n = 23), the abundance of both tNCC and pNCC in uEVs is 4-5 fold higher than in
      CNI-free kidney transplant recipients (n = 13) or healthy volunteers (n = 6). In
      hypertensive kidney transplant recipients, higher abundances of tNCC and pNCC
      prior to treatment with thiazides predicted the blood pressure response to
      thiazides. During thiazide treatment, the abundance of pNCC in uEVs increased in
      responders (n = 10), but markedly decreased in non-responders (n = 8). Thus, our
      results show that CNIs increase the abundance of both tNCC and pNCC in uEVs, and
      these increases correlate with the blood pressure response to thiazides. This
      implies that assessment of NCC in uEVs could represent an alternate method to
      guide anti-hypertensive therapy in kidney transplant recipients.

PMID- 28430813
TI  - Phytoplankton blooms during austral summer in the Ross Sea, Antarctica: Driving
      factors and trophic implications.
AB  - During the austral summer of 2014, an oceanographic cruise was conducted in the
      Ross Sea in the framework of the RoME (Ross Sea Mesoscale Experiment) Project.
      Forty-three hydrological stations were sampled within three different areas: the
      northern Ross Sea (RoME 1), Terra Nova Bay (RoME 2), and the southern Ross Sea
      (RoME 3). The ecological and photophysiological characteristics of the
      phytoplankton were investigated (i.e., size structure, functional groups, PSII
      maximum quantum efficiency, photoprotective pigments), as related to hydrographic
      and chemical features. The aim was to identify the mechanisms that modulate
      phytoplankton blooms, and consequently, the fate of organic materials produced by
      the blooms. The observed biomass standing stocks were very high (e.g., integrated
      chlorophyll-a up to 371 mg m-2 in the top 100 m). Large differences in
      phytoplankton community composition, relative contribution of functional groups
      and photosynthetic parameters were observed among the three subsystems. The
      diatoms (in different physiological status) were the dominant taxa in RoME 1 and
      RoME 3; in RoME 1, a post-bloom phase was identified, whereas in RoME 3, an
      active phytoplankton bloom occurred. In RoME 2, diatoms co-occurred with
      Phaeocystis antarctica, but were vertically segregated by the upper mixed layer,
      with senescent diatoms dominating in the upper layer, and P. antarctica blooming
      in the deeper layer. The dominance of the phytoplankton micro-fraction over the
      whole area and the high Chl-a suggested the prevalence of non-grazed large cells,
      independent of the distribution of the two functional groups. These data
      emphasise the occurrence of significant temporal changes in the phytoplankton
      biomass in the Ross Sea during austral summer. The mechanisms that drive such
      changes and the fate of the carbon production are probably related to the
      variations in the limiting factors induced by the concurrent hydrological
      modifications to the Ross Sea, and they remain to be fully clarified. The
      comparison of conditions observed during summer 2014 and those reported for
      previous years reveal considerably different ecological assets that might be the
      result of current climate change. This suggests that further changes can be
      expected in the future, even at larger oceanic scales.

PMID- 28430814
TI  - How the ovules get enclosed in magnoliaceous carpels.
AB  - Angiosperms distinguish themselves from gymnosperms by their ovules that are
      enclosed before pollination. However, how the ovules get enclosed in angiosperms
      remains a mystery, especially for Magnoliaceae. The only key to this mystery is
      finding a series of carpels transitional from fully closed with enclosed ovules
      to open with naked ovules. We use routine paraffin section technology, LM, SEM to
      document the morphology and anatomy of carpel variation in Michelia figo
      (Magnoliaceae). A series of carpel variations within a single flower of Michelia
      figo (Magnoliaceae) are documented, in which the ovules are exposed in atypical
      carpels. These atypical and typical carpels for the first time demonstrate
      clearly how the naked ovule get enclosed. Each atypical carpel, with naked
      ovules, clearly comprises two parts, namely, subtending foliar part and branches
      bearing ovules, suggesting that a typical carpel is actually an end-product of
      the fusion between the ovuliferous branches and subtending foliar parts. The only
      difference among these carpels is the extent of fusion between these two parts.
      This generalization is in full agreement with the molecular genetic studies on
      angiosperm flowers.

PMID- 28430815
TI  - Soy and fish as features of the Japanese diet and cardiovascular disease risks.
AB  - In the World Health Organization (WHO)-coordinated Cardiovascular Disease and
      Alimentary Comparison Study, isoflavones (I; biomarker for dietary soy) and
      taurine (T; biomarker for dietary fish) in 24-hour-urine (24U) were inversely
      related to coronary heart disease (CHD) mortality. High levels of these
      biomarkers are found in Japanese people, whose CHD mortality is lowest among
      developed countries. We analyzed the association of these biomarkers with
      cardiovascular disease risk in the Japanese to know their health effects within
      one ethnic population. First, to compare the Japanese intake of I and T with
      international intakes, the ratios of 24UI and 24UT to creatinine from the WHO
      Study were divided into quintiles for analysis. The ratio for the Japanese was
      the highest in the highest quintiles for both I and T, reaching 88.1%, far higher
      than the average ratio for the Japanese (26.3%) in the total study population.
      Second, 553 inhabitants of Hyogo Prefecture, Japan, aged 30 to 79 years underwent
      24-U collection and blood analyses. The 24UT and 24UI were divided into tertiles
      and adjusted for age and sex. The highest T tertile, compared with the lowest
      tertile, showed significantly higher levels of high-density lipoprotein
      cholesterol (HDL-C), total cholesterol, 24U sodium (Na) and potassium (K). The
      highest I tertile showed significantly higher folate, 24UNa and 24UK compared
      with the lowest tertile. The highest tertile of both T and I showed significantly
      higher HDL-C, folate, and 24UNa and 24UK compared with the lowest tertile. Thus,
      greater consumption of fish and soy were significantly associated with higher HDL
      C and folate levels, possibly a contributor to Japan having the lowest CHD
      mortality and longest life expectancy among developed countries. As these intakes
      were also associated with a high intake of salt, a low-salt intake of fish and
      soy should be recommended for healthy life expectancy.

PMID- 28430816
TI  - Possible increase in insulin resistance and concealed glucose-coupled potassium
      lowering mechanisms during acute coronary syndrome documented by covariance
      structure analysis.
AB  - OBJECTIVE: Although glucose-insulin-potassium (GIK) therapy ought to be
      beneficial for ischemic heart disease in general, variable outcomes in many
      clinical trials of GIK in acute coronary syndrome (ACS) had a controversial
      impact. This study was designed to examine whether "insulin resistance" is
      involved in ACS and to clarify other potential intrinsic compensatory mechanisms
      for GIK tolerance through highly statistical procedure. METHODS AND RESULTS: We
      compared the degree of insulin resistance during ACS attack and remission phase
      after treatment in individual patients (n = 104). During ACS, homeostasis model
      assessment of insulin resistance (HOMA-IR) values were significantly increased
      (P<0.001), while serum potassium levels were transiently decreased (degree of
      which was indicated by DeltaK) (P<0.001). This finding provides a renewed
      paradox, as DeltaK, a surrogate marker of intrinsic GIK cascade activation,
      probably reflects the validated glucose metabolism during ischemic attack.
      Indeed, multiple regression analysis revealed that plasma glucose level during
      ACS was positively correlated with DeltaK (P = 0.026), whereas HOMA-IR had no
      impact on DeltaK. This positive correlation between DeltaK and glucose was
      confirmed by covariance structure analysis with a strong impact (beta: 0.398, P =
      0.015). Intriguingly, a higher incidence of myocardial infarction relative to
      unstable angina pectoris, as well as a longer hospitalization period were
      observed in patients with larger DeltaK, indicating that DeltaK also reflects
      disease severity of ACS. CONCLUSIONS: Insulin resistance most likely increases
      during ACS; however, DeltaK was positively correlated with plasma glucose level,
      which overwhelmed insulin resistance condition. The present study with covariance
      structure analysis suggests that there are potential endogenous glucose-coupled
      potassium lowering mechanisms, other than insulin, regulating glucose metabolism
      during ACS.

PMID- 28430817
TI  - Kaposi Sarcoma Herpesvirus (KSHV) Latency-Associated Nuclear Antigen (LANA)
      recruits components of the MRN (Mre11-Rad50-NBS1) repair complex to modulate an
      innate immune signaling pathway and viral latency.
AB  - Kaposi Sarcoma Herpesvirus (KSHV), a gamma2-herpesvirus and class 1 carcinogen,
      is responsible for at least three human malignancies: Kaposi Sarcoma (KS),
      Primary Effusion Lymphoma (PEL) and Multicentric Castleman's Disease (MCD). Its
      major nuclear latency protein, LANA, is indispensable for the maintenance and
      replication of latent viral DNA in infected cells. Although LANA is mainly a
      nuclear protein, cytoplasmic isoforms of LANA exist and can act as antagonists of
      the cytoplasmic DNA sensor, cGAS. Here, we show that cytosolic LANA also recruits
      members of the MRN (Mre11-Rad50-NBS1) repair complex in the cytosol and thereby
      inhibits their recently reported role in the sensing of cytoplasmic DNA and
      activation of the NF-kappaB pathway. Inhibition of NF-kappaB activation by
      cytoplasmic LANA is accompanied by increased lytic replication in KSHV-infected
      cells, suggesting that MRN-dependent NF-kappaB activation contributes to KSHV
      latency. Cytoplasmic LANA may therefore support the activation of KSHV lytic
      replication in part by counteracting the activation of NF-kappaB in response to
      cytoplasmic DNA. This would complement the recently described role of cytoplasmic
      LANA in blocking an interferon response triggered by cGAS and thereby promoting
      lytic reactivation. Our findings highlight a second point at which cytoplasmic
      LANA interferes with the innate immune response, as well as the importance of the
      recently discovered role of cytoplasmic MRN complex members as innate sensors of
      cytoplasmic DNA for the control of KSHV replication.

PMID- 28430818
TI  - Comparative genomics of Burkholderia multivorans, a ubiquitous pathogen with a
      highly conserved genomic structure.
AB  - The natural environment serves as a reservoir of opportunistic pathogens. A well
      established method for studying the epidemiology of such opportunists is
      multilocus sequence typing, which in many cases has defined strains predisposed
      to causing infection. Burkholderia multivorans is an important pathogen in people
      with cystic fibrosis (CF) and its epidemiology suggests that strains are acquired
      from non-human sources such as the natural environment. This raises the central
      question of whether the isolation source (CF or environment) or the multilocus
      sequence type (ST) of B. multivorans better predicts their genomic content and
      functionality. We identified four pairs of B. multivorans isolates, representing
      distinct STs and consisting of one CF and one environmental isolate each. All
      genomes were sequenced using the PacBio SMRT sequencing technology, which
      resulted in eight high-quality B. multivorans genome assemblies. The present
      study demonstrated that the genomic structure of the examined B. multivorans STs
      is highly conserved and that the B. multivorans genomic lineages are defined by
      their ST. Orthologous protein families were not uniformly distributed among
      chromosomes, with core orthologs being enriched on the primary chromosome and ST
      specific orthologs being enriched on the second and third chromosome. The ST
      specific orthologs were enriched in genes involved in defense mechanisms and
      secondary metabolism, corroborating the strain-specificity of these virulence
      characteristics. Finally, the same B. multivorans genomic lineages occur in both
      CF and environmental samples and on different continents, demonstrating their
      ubiquity and evolutionary persistence.

PMID- 28430819
TI  - Estimating optimal sparseness of developmental gene networks using a semi
      quantitative model.
AB  - To estimate gene regulatory networks, it is important that we know the number of
      connections, or sparseness of the networks. It can be expected that the
      robustness to perturbations is one of the factors determining the sparseness. We
      reconstruct a semi-quantitative model of gene networks from gene expression data
      in embryonic development and detect the optimal sparseness against perturbations.
      The dense networks are robust to connection-removal perturbation, whereas the
      sparse networks are robust to misexpression perturbation. We show that there is
      an optimal sparseness that serves as a trade-off between these perturbations, in
      agreement with the optimal result of validation for testing data. These results
      suggest that the robustness to the two types of perturbations determines the
      sparseness of gene networks.

PMID- 28430820
TI  - Cardiovascular safety of tiotropium Respimat vs HandiHaler in the routine
      clinical practice: A population-based cohort study.
AB  - The cardiovascular safety of tiotropium Respimat formulation in the routine
      clinical practice is still an open issue. Our aim was to compare the risk of
      acute myocardial infarction and heart rhythm disorders in incident users of
      either tiotropium Respimat or HandiHaler. The study population comprises patients
      aged >=45 years, resident in two Italian regions with a first prescription of
      tiotropium (HandiHaler or Respimat) between 01/07/2011-30/11/2013. The cohort was
      identified through the database of prescriptions reimbursed by the Italian
      National Health Service. Comorbidities and clinical outcomes were obtained from
      hospital records. The primary outcome was the first hospitalization for acute
      myocardial infarction and/or for heart rhythm disorders during the exposure
      period. Hazard ratios were estimated in the propensity score-matched groups
      through Cox regression. After matching, 31,334 patients with incident
      prescription of tiotropium were included. The two groups were balanced with
      regard to baseline characteristics. Similar incidence rates of the primary
      outcome between Respimat and HandiHaler users were identified (adjusted hazard
      ratio 1.02, 95% CI 0.82-1.28). No risk difference between Respimat and HandiHaler
      emerged when considering clinical events separately. This large cohort study
      showed a comparable acute cardiovascular safety profile of the two tiotropium
      formulations.

PMID- 28430822
TI  - Correction: A Burgeoning Crisis? A Nationwide Assessment of the Geography of
      Water Affordability in the United States.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0169488.].

PMID- 28430821
TI  - Dietary DHA/EPA ratio affected tissue fatty acid profiles, antioxidant capacity,
      hematological characteristics and expression of lipid-related genes but not
      growth in juvenile black seabream (Acanthopagrus schlegelii).
AB  - An 8-week feeding trial was conducted to investigate the effects of dietary
      docosahexaenoic to eicosapentaenoic acid ratio (DHA/EPA) on growth performance,
      fatty acid profiles, antioxidant capacity, hematological characteristics and
      expression of some lipid metabolism related genes of juvenile black seabream
      (Acanthopagrus schlegelii) of initial weight 9.47 +/- 0.03 g. Five isonitrogenous
      and isolipidic diets (45% crude protein and 14% crude lipid) were formulated to
      contain graded DHA/EPA ratios of 0.65, 1.16, 1.60, 2.03 and 2.67. There were no
      differences in growth performance and feed utilization among treatments. Fish fed
      higher DHA/EPA ratios had higher malondialdehyde (MDA) contents in serum than
      lower ratios. Serum triacylglycerol (TAG) content was significantly higher in
      fish fed the lowest DHA/EPA ratio. Tissue fatty acid profiles reflected the diets
      despite down-regulation of LC-PUFA biosynthesis genes, fatty acyl desaturase 2
      (fads2) and elongase of very long-chain fatty acids 5 (elovl5), by high DHA/EPA
      ratios. Expression of acetyl-CoA carboxylase alpha (accalpha) and carnitine
      palmitoyl transferase 1A (cpt1a) were up-regulated by high DHA/EPA ratio, whereas
      sterol regulatory element-binding protein-1 (srebp-1) and hormone-sensitive
      lipase (hsl) were down-regulated. Fatty acid synthase (fas), 6-phosphogluconate
      dehydrogenase (6pgd) and peroxisome proliferator-activated receptor alpha
      (pparalpha) showed highest expression in fish fed intermediate (1.16) DHA/EPA
      ratio. Overall, this study indicated that dietary DHA/EPA ratio affected fatty
      acid profiles and significantly influenced lipid metabolism including LC-PUFA
      biosynthesis and other anabolic and catabolic pathways, and also had impacts on
      antioxidant capacity and hematological characteristics.

PMID- 28430823
TI  - Modulation the alternative splicing of GLA (IVS4+919G>A) in Fabry disease.
AB  - While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant
      alternative splicing resulting in Fabry disease has been reported, its molecular
      mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion,
      H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter
      of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex
      with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a
      splicing regulator in cancer cells, could reverse aberrant histone modification
      patterns and disrupt the association of splicing complex with GLA. It could also
      reverse aberrant GLA splicing in a PP1-dependant manner. Our findings revealed
      the alternative splicing mechanism of GLA (IVS4+919G>A), and a potential
      treatment for this specific genetic type of Fabry disease by amiloride in the
      future.

PMID- 28430824
TI  - Suppressors of cytokine signaling in tuberculosis.
AB  - Tuberculosis (TB), a global disease mainly infected by Mycobacterium
      tuberculosis, remains leading public health problem worldwide. Suppressors of
      cytokine signaling (SOCSs) play important roles in the protection against
      microbial infection. However, the relationship between members of the SOCS family
      and tuberculosis infection remains unclear. Using peripheral blood mononuclear
      cells, we investigated the mRNA expression profiles of SOCS subfamilies among
      active TB, latent tuberculosis infection (LTBI), and healthy individuals. Our
      results showed that active tuberculosis subjects had higher levels of SOCS-3
      mRNA, lower expressions of SOCS-2, -4, -5, -6, -7, and cytokine-inducible SH2
      containing protein-1 (CIS-1) mRNAs, but not SOCS-1 mRNA than healthy and LTBI
      subjects. In men, LTBI patients had lower SOCS-3 than healthy subjects, and
      active TB patients had lower levels of SOCS-4, -5, and CIS-1 mRNAs but higher
      levels of SOCS-3 mRNA than healthy subjects. In women, LTBI patients had lower
      SOCS-3 mRNA level than healthy subjects, and active TB patients had lower CIS-1
      mRNA level than healthy subjects. In non-aged adults (< 65 years old), TB
      patients had higher SOCS-3 mRNA and lower levels of SOCS-2, -4, -5, -6, -7, and
      CIS-1 mRNAs; whereas, aged TB patients (>= 65 years old) had lower levels of SOCS
      5 and CIS-1 mRNAs. These data suggest that particular SOCS members and their
      correlative relationships allow discrimination of active TB from healthy and LTBI
      subjects.

PMID- 28430826
TI  - Geographic origin and individual assignment of Shorea platyclados
      (Dipterocarpaceae) for forensic identification.
AB  - The development of timber tracking methods based on genetic markers can provide
      scientific evidence to verify the origin of timber products and fulfill the
      growing requirement for sustainable forestry practices. In this study, the origin
      of an important Dark Red Meranti wood, Shorea platyclados, was studied by using
      the combination of seven chloroplast DNA and 15 short tandem repeats (STRs)
      markers. A total of 27 natural populations of S. platyclados were sampled
      throughout Malaysia to establish population level and individual level
      identification databases. A haplotype map was generated from chloroplast DNA
      sequencing for population identification, resulting in 29 multilocus haplotypes,
      based on 39 informative intraspecific variable sites. Subsequently, a DNA
      profiling database was developed from 15 STRs allowing for individual
      identification in Malaysia. Cluster analysis divided the 27 populations into two
      genetic clusters, corresponding to the region of Eastern and Western Malaysia.
      The conservativeness tests showed that the Malaysia database is conservative
      after removal of bias from population subdivision and sampling effects.
      Independent self-assignment tests correctly assigned individuals to the database
      in an overall 60.60-94.95% of cases for identified populations, and in 98.99
      99.23% of cases for identified regions. Both the chloroplast DNA database and the
      STRs appear to be useful for tracking timber originating in Malaysia. Hence, this
      DNA-based method could serve as an effective addition tool to the existing
      forensic timber identification system for ensuring the sustainably management of
      this species into the future.

PMID- 28430828
TI  - Achieving the Promise of Price Transparency.

PMID- 28430827
TI  - Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry
      and microneme proteins and in parasite division.
AB  - Toxoplasma gondii possesses a highly polarized secretory system, which
      efficiently assembles de novo micronemes and rhoptries during parasite
      replication. These apical secretory organelles release their contents into host
      cells promoting parasite invasion and survival. Using a CreLox-based inducible
      knock-out strategy and the ddFKBP over-expression system, we unraveled novel
      functions of the clathrin adaptor complex TgAP1. First, our data indicate that
      AP1 in T. gondii likely functions as a conserved heterotetrameric complex
      composed of the four subunits gamma, beta, MU1, sigma1 and interacts with known
      regulators of clathrin-mediated vesicular budding such as the unique ENTH-domain
      containing protein, which we named Epsin-like protein (TgEpsL). Disruption of the
      MU1 subunit resulted in the mis-sorting of microneme proteins at the level of the
      Trans-Golgi-Network (TGN). Furthermore, we demonstrated that TgAP1 regulates
      rhoptry biogenesis by activating rhoptry protein exit from the TGN, but also
      participates in the post-Golgi maturation process of preROP compartments into
      apically anchored club-shaped mature organelles. For this latter activity, our
      data indicate a specific functional relationship between TgAP1 and the Rab5A
      positive endosome-like compartment. In addition, we unraveled an original role
      for TgAP1 in the regulation of parasite division. APMU1-depleted parasites
      undergo normal daughter cell budding and basal complex assembly but fail to
      segregate at the end of cytokinesis.

PMID- 28430829
TI  - Effect of a Price Transparency Intervention in the Electronic Health Record on
      Clinician Ordering of Inpatient Laboratory Tests: The PRICE Randomized Clinical
      Trial.
AB  - Importance: Many health systems are considering increasing price transparency at
      the time of order entry. However, evidence of its impact on clinician ordering
      behavior is inconsistent and limited to single-site evaluations of shorter
      duration. Objective: To test the effect of displaying Medicare allowable fees for
      inpatient laboratory tests on clinician ordering behavior over 1 year. Design,
      Setting, and Participants: The Pragmatic Randomized Introduction of Cost data
      through the electronic health record (PRICE) trial was a randomized clinical
      trial comparing a 1-year intervention to a 1-year preintervention period, and
      adjusting for time trends and patient characteristics. The trial took place at 3
      hospitals in Philadelphia between April 2014 and April 2016 and included 98 529
      patients comprising 142 921 hospital admissions. Interventions: Inpatient
      laboratory test groups were randomly assigned to display Medicare allowable fees
      (30 in intervention) or not (30 in control) in the electronic health record. Main
      Outcomes and Measures: Primary outcome was the number of tests ordered per
      patient-day. Secondary outcomes were tests performed per patient-day and Medicare
      associated fees. Results: The sample included 142 921 hospital admissions
      representing patients who were 51.9% white (74 165), 38.9% black (55 526), and
      56.9% female (81 291) with a mean (SD) age of 54.7 (19.0) years. Preintervention
      trends of order rates among the intervention and control groups were similar. In
      adjusted analyses of the intervention group compared with the control group over
      time, there were no significant changes in overall test ordering behavior (0.05
      tests ordered per patient-day; 95% CI, -0.002 to 0.09; P = .06) or associated
      fees ($0.24 per patient-day; 95% CI, -$0.42 to $0.91; P = .47). Exploratory
      subset analyses found small but significant differences in tests ordered per
      patient-day based on patient intensive care unit (ICU) stay (patients with ICU
      stay: -0.16; 95% CI, -0.31 to -0.01; P = .04; patients without ICU stay: 0.13;
      95% CI, 0.08-0.17; P < .001) and the magnitude of associated fees (top quartile
      of tests based on fee value: -0.01; 95% CI, -0.02 to -0.01; P = .04; bottom
      quartile: 0.03; 95% CI, 0.002-0.06; P = .04). Adjusted analyses of tests that
      were performed found a small but significant overall increase in the intervention
      group relative to the control group over time (0.08 tests performed per patient
      day, 95% CI, 0.03-0.12; P < .001). Conclusions and Relevance: Displaying Medicare
      allowable fees for inpatient laboratory tests did not lead to a significant
      change in overall clinician ordering behavior or associated fees. Trial
      Registration: clinicaltrials.gov Identifier: NCT02355496.

PMID- 28430830
TI  - Assessment of Global Kidney Health Care Status.
AB  - Importance: Kidney disease is a substantial worldwide clinical and public health
      problem, but information about available care is limited. Objective: To collect
      information on the current state of readiness, capacity, and competence for the
      delivery of kidney care across countries and regions of the world. Design,
      Setting, and Participants: Questionnaire survey administered from May to
      September 2016 by the International Society of Nephrology (ISN) to 130 ISN
      affiliated countries with sampling of key stakeholders (national nephrology
      society leadership, policy makers, and patient organization representatives)
      identified by the country and regional nephrology leadership through the ISN.
      Main Outcomes and Measures: Core areas of country capacity and response for
      kidney care. Results: Responses were received from 125 of 130 countries (96%),
      including 289 of 337 individuals (85.8%, with a median of 2 respondents
      [interquartile range, 1-3]), representing an estimated 93% (6.8 billion) of the
      world's population of 7.3 billion. There was wide variation in country readiness,
      capacity, and response in terms of service delivery, financing, workforce,
      information systems, and leadership and governance. Overall, 119 (95%), 95 (76%),
      and 94 (75%) countries had facilities for hemodialysis, peritoneal dialysis, and
      kidney transplantation, respectively. In contrast, 33 (94%), 16 (45%), and 12
      (34%) countries in Africa had facilities for hemodialysis, peritoneal dialysis,
      and kidney transplantation, respectively. For chronic kidney disease (CKD)
      monitoring in primary care, serum creatinine with estimated glomerular filtration
      rate and proteinuria measurements were reported as always available in only 21
      (18%) and 9 (8%) countries, respectively. Hemodialysis, peritoneal dialysis, and
      transplantation services were funded publicly and free at the point of care
      delivery in 50 (42%), 48 (51%), and 46 (49%) countries, respectively. The number
      of nephrologists was variable and was low (<10 per million population) in Africa,
      the Middle East, South Asia, and Oceania and South East Asia (OSEA) regions.
      Health information system (renal registry) availability was limited, particularly
      for acute kidney injury (8 countries [7%]) and nondialysis CKD (9 countries
      [8%]). International acute kidney injury and CKD guidelines were reportedly
      accessible in 52 (45%) and 62 (52%) countries, respectively. There was relatively
      low capacity for clinical studies in developing nations. Conclusions and
      Relevance: This survey demonstrated significant interregional and intraregional
      variability in the current capacity for kidney care across the world, including
      important gaps in services and workforce. Assuming the responses accurately
      reflect the status of kidney care in the respondent countries, the findings may
      be useful to inform efforts to improve the quality of kidney care worldwide.

PMID- 28430831
TI  - Worldwide Preparedness for Kidney Health Care.

PMID- 28430832
TI  - Blood Pressure With Nitrate Exposure: Back-to-Basics With Fresh Fruits and
      Vegetables.

PMID- 28430825
TI  - Discovery and fine-mapping of adiposity loci using high density imputation of
      genome-wide association studies in individuals of African ancestry: African
      Ancestry Anthropometry Genetics Consortium.
AB  - Genome-wide association studies (GWAS) have identified >300 loci associated with
      measures of adiposity including body mass index (BMI) and waist-to-hip ratio
      (adjusted for BMI, WHRadjBMI), but few have been identified through screening of
      the African ancestry genomes. We performed large scale meta-analyses and
      replications in up to 52,895 individuals for BMI and up to 23,095 individuals for
      WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC)
      using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and
      low frequency variants in the low linkage disequilibrium African ancestry
      genomes. In the sex-combined analyses, we identified one novel locus
      (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5*10-8:
      seven for BMI, and one for WHRadjBMI in African ancestry individuals. An
      additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined
      with European GWAS. In the sex-stratified analyses, we identified three novel
      loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for
      WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of
      African ancestry or both African and European ancestry. For four of the novel
      variants, the minor allele frequency was low (<5%). In the trans-ethnic fine
      mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P
      < 0.05 adjusted for effective number of variants per locus) from the African
      ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI
      loci contained <= 20 variants in the credible sets that jointly account for 99%
      posterior probability of driving the associations. The lead variants in 13 of
      these loci had a high probability of being causal. As compared to our previous
      HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350
      African ancestry individuals, respectively, our results suggest that 1000 Genomes
      imputation showed modest improvement in identifying GWAS loci including low
      frequency variants. Trans-ethnic meta-analyses further improved fine mapping of
      putative causal variants in loci shared between the African and European ancestry
      populations.

PMID- 28430834
TI  - Erratum.

PMID- 28430833
TI  - On the Need for Quantitative Bias Analysis in the Peer-Review Process.
AB  - Peer review is central to the process through which epidemiologists generate
      evidence to inform public health and medical interventions. Reviewers thereby act
      as critical gatekeepers to high-quality research. They are asked to carefully
      consider the validity of the proposed work or research findings by paying careful
      attention to the methodology and critiquing the importance of the insight gained.
      However, although many have noted problems with the peer-review system for both
      manuscripts and grant submissions, few solutions have been proposed to improve
      the process. Quantitative bias analysis encompasses all methods used to quantify
      the impact of systematic error on estimates of effect in epidemiologic research.
      Reviewers who insist that quantitative bias analysis be incorporated into the
      design, conduct, presentation, and interpretation of epidemiologic research could
      substantially strengthen the process. In the present commentary, we demonstrate
      how quantitative bias analysis can be used by investigators and authors,
      reviewers, funding agencies, and editors. By utilizing quantitative bias analysis
      in the peer-review process, editors can potentially avoid unnecessary rejections,
      identify key areas for improvement, and improve discussion sections by shifting
      from speculation on the impact of sources of error to quantification of the
      impact those sources of bias may have had.

PMID- 28430836
TI  - Test-Retest Reliability of Common Behavioral Decision Making Tasks.
AB  - Objective: To examine test-retest reliability of common behavioral decision
      making tasks. Method: A total of 98 undergraduate students completed two
      administrations of the Iowa Gambling Task (IGT), Balloon Analogue Risk Task
      (BART), Columbia Card Task (CCT), and Game of Dice Task (GDT), three weeks apart.
      Results: The BART, CCT, and GDT showed moderately strong correlations across
      time. On the IGT, no correlations were seen between Time 1 Trials 1-40 and Time 2
      performance; however, weak correlations were observed between Time 1 Trials 41
      100 and Time 2 performance. Paired-samples t-tests indicated participants were
      riskier at Time 1 than Time 2 on the IGT and GDT, but riskier at Time 2 on the
      BART. Conclusions: The BART, CCT, and GDT showed moderate test-retest
      reliability, with the IGT showing weak reliability during the decision making
      under risk trials only. Implications for repeated test administration in clinical
      and non-clinical settings are discussed.

PMID- 28430837
TI  - Hypertensive Patients That Respond to Aldosterone Antagonists May Have a
      Nonclassical 11beta-HSD2 Deficiency.

PMID- 28430835
TI  - Relationship Between Urinary Nitrate Excretion and Blood Pressure in the
      InChianti Cohort.
AB  - BACKGROUND: Inorganic nitrate from the oxidation of endogenously synthesized
      nitric oxide (NO) or consumed in the diet can be reduced to NO via a complex
      enterosalivary circulation pathway. The relationship between total nitrate
      exposure by measured urinary nitrate excretion and blood pressure in a large
      population sample has not been assessed previously. METHODS: For this cross
      sectional study, 24-hour urinary nitrate excretion was measured by
      spectrophotometry in the 919 participants from the InChianti cohort at baseline
      and blood pressure measured with a mercury sphygmomanometer. RESULTS: After
      adjusting for age and sex only, diastolic blood pressure was 1.9 mm Hg lower in
      subjects with >=2 mmol urinary nitrate excretion compared with those excreting <1
      mmol nitrate in 24 hours: systolic blood pressure was 3.4 mm Hg (95% confidence
      interval (CI): -3.5 to -0.4) lower in subjects for the same comparison. Effect
      sizes in fully adjusted models (for age, sex, potassium intake, use of
      antihypertensive medications, diabetes, HS-CRP, or current smoking status) were
      marginally larger: systolic blood pressure in the >=2 mmol urinary nitrate
      excretion group was 3.9 (CI: -7.1 to -0.7) mm Hg lower than in the comparison <1
      mmol excretion group. CONCLUSIONS: Modest differences in total nitrate exposure
      are associated with lower blood pressure. These differences are at least
      equivalent to those seen from substantial (100 mmol) reductions in sodium intake.

PMID- 28430838
TI  - Elevated Pulse Pressure Levels Are Associated With Increased In-Hospital
      Mortality in Acute Spontaneous Intracerebral Hemorrhage.
AB  - OBJECTIVES: Clinical outcome after intracerebral hemorrhage (ICH) remains poor.
      Definitive phase-3 trials in ICH have failed to demonstrate improved outcomes
      with intensive systolic blood pressure (SBP) lowering. We sought to determine
      whether other BP parameters-diastolic BP (DBP), pulse pressure (PP), and mean
      arterial pressure (MAP)-showed an association with clinical outcome in ICH.
      METHODS: We retrospectively analyzed a prospective cohort of 672 patients with
      spontaneous ICH and documented demographic characteristics, stroke severity, and
      neuroimaging parameters. Consecutive hourly BP recordings allowed for computation
      of SBP, DBP, PP, and MAP. Threshold BP values that transitioned patients from
      survival to death were determined from ROC curves. Using in-hospital mortality as
      outcome, BP parameters were evaluated with multivariable logistic regression
      analysis. RESULTS: Patients who died during hospitalization had higher mean PP
      compared to survivors (68.5 +/- 16.4 mm Hg vs. 65.4 +/- 12.4 mm Hg; P = 0.032).
      The following admission variables were associated with significantly higher in
      hospital mortality (P < 0.001): poorer admission clinical condition,
      intraventricular hemorrhage, and increased admission normalized hematoma volume.
      ROC analysis showed that mean PP dichotomized at 72.17 mm Hg, provided a
      transition point that maximized sensitivity and specific for mortality. The
      association of this increased dichotomized PP with higher in-hospital mortality
      was maintained in multivariable logistic regression analysis (odds ratio, 3.0;
      95% confidence interval, 1.7-5.3; P < 0.001) adjusting for potential confounders.
      CONCLUSION: Widened PP may be an independent predictor for higher mortality in
      ICH. This association requires further study.

PMID- 28430839
TI  - Pathological Imitative Behavior and Response Preparation in Schizophrenia.
AB  - Introduction: Pathological imitative behavior (ehopraxia) is occasionally
      observed in schizophrenia patients. However, only a severe form of echopraxia can
      be detected with the help of a direct observation. Therefore, our goal was to
      study a latent form of pathological imitative behavior in this disorder, which is
      indicated by an increase of imitative tendencies. Method: In our study, 14
      schizophrenia patients and 15 healthy subjects were employed in two tasks: (a) in
      an imitative task they had to copy a hand action seen on a screen; (b) in a
      counter-imitative task they had to make a different movement (which involves an
      inhibition of prepotent imitative tendency that is impaired in case of
      pathological imitative behavior). Imitative tendencies were assessed by an
      interference score - a difference between counter-imitative and imitative
      response parameters. We also studied a response preparation in both groups by
      employing precueing probabilistic information. Results: Our results revealed that
      schizophrenia patients were able to employ probabilistic information to prepare
      properly not only the imitative, but also the counter-imitative responses, the
      same as the healthy subjects did. Nevertheless, we detected increased prepotent
      imitative tendencies in schizophrenia patients, what indicates the latent
      pathological imitative behavior in case of this disorder. Conclusions: The
      obtained results suggest that in the case of schizophrenia problems with
      pathological imitative behavior more likely occurred in executive rather than in
      the preparatory stage of response. Our findings can help to detect a latent
      echopraxia in schizophrenia patients that cannot be revealed by direct
      observation.

PMID- 28430840
TI  - Checkpoint-dependent phosphorylation of Med1/TRAP220 in response to DNA damage.
AB  - Mediator complex subunit 1 (Med1)/Thyroid hormone receptor-associated protein 220
      (TRAP220), an essential component of thyroid hormone receptor-associated proteins
      (TRAP)/mediator, plays important roles in hormone responses and tumorigenesis.
      However, the role of Med1 in the DNA damage response has not been studied. In
      this study, we found that DNA damage, resulted from gamma-irradiation,
      ultraviolet (UV)-irradiation, or hydroxyurea, induced phosphorylation of Med1 in
      vivo. Phosphorylation of Med1 was abrogated by either caffeine or wortmannin
      treatment, suggesting that Med1 is phosphorylated through the DNA damage
      checkpoint pathway. A checkpoint kinase 1 (Chk1)/checkpoint kinase 2 (Chk2)
      consensus phosphorylation motif was identified at Serine 671 of Med1 and Ser671
      motif was primarily phosphorylated by Chk2 in vitro. Moreover, the in vivo
      phosphorylation of Med1 was abrogated by a Chk2 inhibitor, and physical
      interaction between Chk2 and Med1 was observed, confirming that Chk2 is
      responsible for Med1 phosphorylation upon DNA damage. These results suggest that
      Med1 is a novel target for the DNA damage checkpoint pathway and may participate
      in the DNA damage response. Consistent with this notion, knockdown of Med1
      expression caused a significant increase in cellular sensitivity to UV
      irradiation. Moreover, microarray analysis revealed that the UV-induced
      activation of the transcription of important regulators of cell cycle control and
      DNA repair, including p21, Gadd45, Rad50, DnaJ, and RecQL, was impaired upon Med1
      knockdown. Taken together, our data suggest that Med1 is a novel target for Chk2
      mediated phosphorylation and may play a role in cellular DNA damage responses by
      mediating proper induction of gene transcription upon DNA damage.

PMID- 28430841
TI  - Associations of Early- and Later-Childhood Poverty With Child Cognitive Function
      in Indonesia: Effect Decomposition in the Presence of Exposure-Induced Mediator
      Outcome Confounding.
AB  - The amount of family financial resources available in early life influences child
      health and development. Using data from the 2000 and 2007 waves of the Indonesian
      Family Life Survey, we estimated the associations of early-life poverty (at age
      <7 years) and poverty in later childhood (at age 7-14 years) with cognitive
      function at age 7-14 years. Our analysis provided little support for the idea
      that an early intervention to support household income has a larger effect than
      intervention later in childhood; both seemed equally important. We also
      decomposed the effect of poverty at age <7 years into direct and indirect effects
      mediated through poverty and schooling/home environment at age 7-14 years. For
      decomposing the effects, we used 3 approaches: 1) joint mediators, 2) path
      specific, and 3) intervention analog. Being exposed to poverty before age 7 years
      had a larger direct effect (difference in cognitive function z score) on child
      cognitive function at age 7-14 years (i.e., joint mediators beta = -0.07, 95%
      confidence interval: -0.12, -0.02) than the indirect effects mediated through
      later poverty at age 7-14 years (beta = -0.01, 95% confidence interval: -0.04,
      0.01) and school attendance/home environment at age 7-14 years. The effect of
      poverty on cognitive function was small; nevertheless, financial intervention may
      still benefit children's cognitive function.

PMID- 28430842
TI  - A New Method for Partial Correction of Residual Confounding in Time-Series and
      Other Observational Studies.
AB  - Methods exist to detect residual confounding in epidemiologic studies. One
      requires a negative control exposure with 2 key properties: 1) conditional
      independence of the negative control and the outcome (given modeled variables)
      absent confounding and other model misspecification, and 2) associations of the
      negative control with uncontrolled confounders and the outcome. We present a new
      method to partially correct for residual confounding: When confounding is present
      and our assumptions hold, we argue that estimators from models that include a
      negative control exposure with these 2 properties tend to be less biased than
      those from models without it. Using regression theory, we provide theoretical
      arguments that support our claims. In simulations, we empirically evaluated the
      approach using a time-series study of ozone effects on asthma emergency
      department visits. In simulations, effect estimators from models that included
      the negative control exposure (ozone concentrations 1 day after the emergency
      department visit) had slightly or modestly less residual confounding than those
      from models without it. Theory and simulations show that including the negative
      control can reduce residual confounding, if our assumptions hold. Our method
      differs from available methods because it uses a regression approach involving an
      exposure-based indicator rather than a negative control outcome to partially
      correct for confounding.

PMID- 28430843
TI  - Carotid Body Denervation Markedly Improves Survival in Rats With Hypertensive
      Heart Failure.
AB  - BACKGROUND: Hypertension is a major cause of heart failure. Excessive
      sympathoexcitation in patients with heart failure leads to poor prognosis. Since
      carotid body denervation (CBD) has been shown to reduce sympathetic nerve
      activity in animal models of hypertension and heart failure, we examined if
      bilateral CBD attenuates the progression of hypertensive heart failure and
      improves survival. METHODS: We randomly allocated Dahl salt-sensitive rats fed a
      high-salt diet from 6 weeks of age into CBD (n = 31) and sham-operation (SHAM; n
      = 50) groups, and conducted CBD or SHAM at 7 weeks of age. We examined the time
      course of 24-hour urinary norepinephrine (uNE) excretion, blood pressure (BP) and
      the percent fractional shortening assessed by echocardiography, and estimated the
      pressure-natriuresis relationship at 14 weeks of age. Finally, we assessed
      hemodynamics, histological findings, and survival at 16 weeks of age. RESULTS:
      Compared to SHAM, CBD significantly reduced 24-hour uNE at 12, 14, and 16 weeks
      of age, shifted the pressure-natriuresis relationship leftward without changing
      its slope, and attenuated the increase in BP. CBD preserved percent fractional
      shortening (34.2 +/- 1.2 vs. 29.1 +/- 1.3%, P < 0.01) and lowered left
      ventricular end-diastolic pressure (5.0 +/- 0.9 vs. 9.0 +/- 1.4 mm Hg, P < 0.05).
      Furthermore, CBD significantly attenuated myocardial hypertrophy (P < 0.01) and
      fibrosis (P < 0.01). Consequently, CBD markedly improved survival (relative risk
      reduction: 64.8%). CONCLUSIONS: CBD attenuated the progression of hypertension
      and worsening of heart failure possibly through sympathoinhibition, and markedly
      improved survival in a rat model of hypertensive heart failure.

PMID- 28430845
TI  - Accuracy-Limiting Factor of Home Blood Pressure Monitors?

PMID- 28430844
TI  - Effects of Antiretroviral Therapy and Depressive Symptoms on All-Cause Mortality
      Among HIV-Infected Women.
AB  - Depression affects up to 30% of human immunodeficiency virus (HIV)-infected
      individuals. We estimated joint effects of antiretroviral therapy (ART)
      initiation and depressive symptoms on time to death using a joint marginal
      structural model and data from a cohort of HIV-infected women from the Women's
      Interagency HIV Study (conducted in the United States) from 1998-2011. Among 848
      women contributing 6,721 years of follow-up, 194 participants died during follow
      up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative
      mortality curves indicated greatest mortality for women who reported depressive
      symptoms and had not initiated ART. The hazard ratio for depressive symptoms was
      3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI:
      0.31, 0.70). Using a reference category of women without depressive symptoms who
      had initiated ART, the hazard ratio for women with depressive symptoms who had
      initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive
      symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81).
      Among women reporting depressive symptoms who had not started ART, the hazard
      ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART
      initiation on mortality, as well as a harmful effect of depressive symptoms, in a
      cohort of HIV-infected women.

PMID- 28430846
TI  - A Case of Bariatric Surgery-related Wernicke-Korsakoff Syndrome with Persisting
      Anterograde Amnesia.
AB  - Objective: To describe the theoretical and clinical implications of the
      neuropsychological evaluation of a case of bariatric surgery-related Wernicke
      Korsakoff syndrome. Method: The patient was a 37-year old, female, bilingual,
      bachelor's degree educated, Mexican American public relations consultant without
      preexisting psychiatric, neurological, or substance abuse history. Recovery from
      laparoscopic sleeve gastrectomy surgery for morbid obesity was complicated by
      intraabdominal abscess, multibacterial infection, and prolonged nausea and
      vomiting. About 15 weeks post-surgery she was diagnosed with Wernicke's
      encephalopathy. She had a positive response to thiamine supplement but was left
      with persisting self-reported memory problems that were confirmed by family
      members. Multiple neuroimaging studies were all normal. Results: A
      neuropsychological evaluation at 14 months post-surgery revealed anterograde
      amnesia for verbal and visual-perceptual material. There was no clear period of
      temporally graded retrograde amnesia. Scores on tests of visual-perceptual,
      language, fine motor, and executive functions were unimpaired. She had awareness
      of her neurocognitive impairment, but did not exhibit emotional distress. Follow
      up neuropsychological evaluation at 17 months showed a similar neurocognitive
      profile with increased emotional distress. Conclusions: Her preserved executive
      functioning is theoretically important as it supports arguments that such
      impairment in alcohol use-related Korsakoff syndrome derives from the toxic
      effects of the prolonged misuse of alcohol and not vitamin deficiency. From a
      clinical perspective, neuropsychological evaluation of thiamine treated,
      bariatric surgery-related, Wernicke's encephalopathy cases is indicated if there
      is suspicion of residual memory impairment.

PMID- 28430847
TI  - Invited Commentary: Bias Attenuation and Identification of Causal Effects With
      Multiple Negative Controls.
AB  - In this commentary, we describe several extensions to the interesting and
      important negative control exposure approach for partial confounding adjustment
      in time-series analysis proposed by Flanders et al. (Am J Epidemiol.
      2017;185(10):941-949). Specifically, by leveraging the availability of exposure
      time series, we show that under certain additional fairly reasonable assumptions,
      one can incorporate both past and future exposures as multiple negative control
      exposures to further attenuate confounding bias. We further describe 2 specific
      settings in which multiple controls can be used to fully account for confounding
      bias; the first assumes a forward-in-time version of the familiar autoregressive
      model for the exposure time series, while the second combines a negative control
      exposure with a negative control outcome for joint indirect adjustment of
      confounding. We briefly illustrate how one might apply our proposed framework in
      time-series studies. Both the original method of Flanders et al. and our proposed
      extensions are particularly well-suited for time-series data such as the air
      pollution study considered in their paper, and as such should be considered in
      routine environmental health studies.

PMID- 28430848
TI  - An Assessment of the Accuracy of Home Blood Pressure Monitors When Used in Device
      Owners.
AB  - OBJECTIVE: To examine the accuracy of home blood pressure (BP) devices, on their
      owners, compared to auscultatory reference standard BP measurements. METHODS:
      Eighty-five consecutive consenting subjects >=18 years of age, who owned an
      oscillometric home BP device (wrist or upper-arm device), with BP levels between
      80-220/50-120 mm Hg, and with arm circumferences between 25-43 cm were studied.
      Pregnancy and atrial fibrillation were exclusion criteria. Device measurements
      from each subject's home BP device were compared to simultaneous 2-observer
      auscultation using a mercury sphygmomanometer. Between-group mean comparisons
      were conducted using paired t-tests. The proportion of patients with device-to
      auscultatory differences of >=5, 10, and 15 mm Hg were tabulated and predictors
      of systolic and diastolic BP differences were identified using linear regression.
      RESULTS: Mean age was 66.4 +/- 11.0 years, mean arm circumference was 32.7 +/-
      3.7 cm, 54% were female and 78% had hypertension. Mean BPs were 125.7 +/-
      14.0/73.9 +/- 10.4 mm Hg for home BP devices vs. 129.0 +/- 14.7/72.9 +/- 9.3 for
      auscultation (difference of -3.3 +/- 7.3/0.9 +/- 6.1; P values <0.0001 for
      systolic and 0.17 for diastolic). The proportion of devices with systolic or
      diastolic BP differences from auscultation of >=5, 10, and 15 mm Hg was 69%, 29%,
      and 7%, respectively. Increasing arm circumference was a statistically
      significant predictor of higher systolic (parameter estimate 0.61 per cm
      increase; P value 0.004) and diastolic (0.38; 0.03) BP. CONCLUSIONS: Although
      mean differences from 2-observer auscultation were acceptable, when tested on
      their owners, most home BP devices were not accurate to within 5 mm Hg. Ensuring
      acceptable accuracy of the device-owner pairing should be prioritized.

PMID- 28430849
TI  - Performance and Symptom Validity Testing as a Function of Medical Board
      Evaluation in U.S. Military Service Members with a History of Mild Traumatic
      Brain Injury.
AB  - Objective: The study was designed to replicate and extend pervious findings
      demonstrating the high rates of invalid neuropsychological testing in military
      service members (SMs) with a history of mild traumatic brain injury (mTBI)
      assessed in the context of a medical evaluation board (MEB). Method: Two hundred
      thirty-one active duty SMs (61 of which were undergoing an MEB) underwent
      neuropsychological assessment. Performance validity (Word Memory Test) and
      symptom validity (MMPI-2-RF) test data were compared across those evaluated
      within disability (MEB) and clinical contexts. Results: As with previous studies,
      there were significantly more individuals in an MEB context that failed
      performance (MEB = 57%, non-MEB = 31%) and symptom validity testing (MEB = 57%,
      non-MEB = 22%) and performance validity testing had a notable affect on cognitive
      test scores. Performance and symptom validity test failure rates did not vary as
      a function of the reason for disability evaluation when divided into behavioral
      versus physical health conditions. Conclusions: These data are consistent with
      past studies, and extends those studies by including symptom validity testing and
      investigating the effect of reason for MEB. This and previous studies demonstrate
      that more than 50% of SMs seen in the context of an MEB will fail performance
      validity tests and over-report on symptom validity measures. These results
      emphasize the importance of using both performance and symptom validity testing
      when evaluating SMs with a history of mTBI, especially if they are being seen for
      disability evaluations, in order to ensure the accuracy of cognitive and
      psychological test data.

PMID- 28430850
TI  - Trends in Hospitalization for Hypertensive Emergency, and Relationship of End
      Organ Damage With In-Hospital Mortality.
AB  - BACKGROUND: There are no comprehensive guidelines on management of hypertensive
      emergency (HTNE) and complications. Despite advances in antihypertensive
      medications HTNE is accompanied with significant morbidity and mortality.
      METHODS: We queried the 2002-2012 nationwide inpatient sample database to
      identify patients with HTNE. Trends in incidence of HTNE and in-hospital
      mortality were analyzed. Logistic regression analysis was used to assess the
      relationship between end-organ complications and in-hospital mortality. RESULTS:
      Between 2002 and 2012, 129,914 admissions were included. Six hundred and thirty
      (0.48%) patients died during their hospital stay. There was an increase in the
      number of HTNE admissions (9,511-15,479; Ptrend < 0.001) with concurrent
      reduction of in-hospital mortality (0.8-0.3%; Ptrend < 0.001) by the year 2012
      compared to 2002. Patients who died during hospitalization were older, had longer
      length of stay, higher cost of stay, more comorbidities, and higher risk scores.
      Presence of acute cardiorespiratory failure [adjusted odds ratio (OR), 15.8; 95%
      confidence interval (CI), 13.2-18.9], stroke or transient ischemia attack (TIA)
      (adjusted OR, 7.9; 95% CI, 6.3-9.9), chest pain (adjusted OR, 5.9; 95% CI, 4.4
      7.7), stroke/TIA (adjusted OR, 5.9; 95% CI, 4.5-7.7), and aortic dissection
      (adjusted OR, 5.9; 95% CI, 2.8-12.4) were most predictive of higher in-hospital
      mortality in addition to factors such as age, aortic dissection, acute myocardial
      infarction, acute renal failure, and presence of neurological symptoms.
      CONCLUSION: A rising trend in hospitalization for HTNE, with an overall decrease
      in in-hospital mortality was observed from 2002 to 2012, possibly related to
      changes in coding practices and improved management. Presence of acute
      cardiorespiratory failure, stroke/TIA, chest pain, and aortic dissection were
      most predictive of higher hospital mortality.

PMID- 28430851
TI  - Accuracy of Offspring-Reported Parental Hip Fractures: A Novel Population-Based
      Parent-Offspring Record Linkage Study.
AB  - The objective of this study was to test the validity of offspring-reported
      parental hip fracture in a unique bone mineral density (BMD) registry linked to
      administrative databases spanning 4 decades. Population-based data were from
      Manitoba, Canada, and included hospital abstracts, health insurance
      registrations, and the provincewide BMD registry. The cohort included individuals
      aged >=40 years with BMD tests and self-reports of parental hip fracture between
      2006 and 2014. Population registry data for 1966-2014 were used to link offspring
      with their parents, and hospital records were used to ascertain parental
      fractures. Overall, 8,112 offspring met the inclusion criteria; 13.6% had a
      parental hip fracture diagnosis in administrative data during an average of 32.9
      years of follow-up. Agreement between parental hip fracture from offspring
      reports and diagnoses in administrative data was good (kappa = 0.68). The
      sensitivity of offspring reports was 0.70 (95% confidence interval: 0.67, 0.73),
      and specificity was 0.96 (95% confidence interval: 0.96, 0.97). Offspring
      characteristics associated with disagreement included male sex, northern rural
      residence, early BMD test year, and longer interval between BMD test and parental
      hip fracture diagnosis. This proof-of-concept study focused on hip fractures, but
      use of record linkage techniques to validate offspring-reported parental
      information can be extended to other conditions.

PMID- 28430852
TI  - Thulium fiber laser recanalization of occluded ventricular catheters in an ex
      vivo tissue model.
AB  - Hydrocephalus is a chronic medical condition that occurs in individuals who are
      unable to reabsorb cerebrospinal fluid (CSF) created within the ventricles of the
      brain. Treatment requires excess CSF to be diverted from the ventricles to
      another part of the body, where it can be returned to the vascular system via a
      shunt system beginning with a catheter within the ventricle. Catheter failures
      due to occlusion by brain tissues commonly occur and require surgical replacement
      of the catheter. In this preliminary study, minimally invasive clearance of
      occlusions is explored using an experimental thulium fiber laser (TFL), with
      comparison to a conventional holmium: yttrium aluminium garnet (YAG) laser. The
      TFL utilizes smaller optical fibers ( < 200 - ? m OD) compared with holmium laser
      ( > 450 - ? m OD), providing critical extra cross-sectional space within the 1.2
      mm-inner-diameter ventricular catheter for simultaneous application of an
      endoscope for image guidance and a saline irrigation tube for visibility and
      safety. TFL ablation rates using 100 - ? m core fiber, 33-mJ pulse energy, 500 -
      ? s pulse duration, and 20- to 200-Hz pulse rates were compared to holmium laser
      using a 270 - ? m core fiber, 325-mJ, 300 - ? s , and 10 Hz. A tissue occluded
      catheter model was prepared using coagulated egg white within clear silicone
      tubing. An optimal TFL pulse rate of 50 Hz was determined, with an ablation rate
      of 150 ?? ? m / s and temperature rise outside the catheter of ? 10  degrees  C .
      High-speed camera images were used to explore the

PMID- 28430853
TI  - Laplacian manifold regularization method for fluorescence molecular tomography.
AB  - Sparse regularization methods have been widely used in fluorescence molecular
      tomography (FMT) for stable three-dimensional reconstruction. Generally, ? 1 
      regularization-based methods allow for utilizing the sparsity nature of the
      target distribution. However, in addition to sparsity, the spatial structure
      information should be exploited as well. A joint ? 1 and Laplacian manifold
      regularization model is proposed to improve the reconstruction performance, and
      two algorithms (with and without Barzilai-Borwein strategy) are presented to
      solve the regularization model. Numerical studies and in vivo experiment
      demonstrate that the proposed Gradient projection-resolved Laplacian manifold
      regularization method for the joint model performed better than the comparative
      algorithm for ? 1 minimization method in both spatial aggregation and location
      accuracy.

PMID- 28430854
TI  - Dynamic modeling and network approaches for omics time course data: overview of
      computational approaches and applications.
AB  - Inferring networks and dynamics of genes, proteins, cells and other biological
      entities from high-throughput biological omics data is a central and challenging
      issue in computational and systems biology. This is essential for understanding
      the complexity of human health, disease susceptibility and pathogenesis for
      Predictive, Preventive, Personalized and Participatory (P4) system and precision
      medicine. The delineation of the possible interactions of all genes/proteins in a
      genome/proteome is a task for which conventional experimental techniques are ill
      suited. Urgently needed are rapid and inexpensive computational and statistical
      methods that can identify interacting candidate disease genes or drug targets out
      of thousands that can be further investigated or validated by experimentations.
      Moreover, identifying biological dynamic systems, and simultaneously estimating
      the important kinetic structural and functional parameters, which may not be
      experimentally accessible could be important directions for drug-disease-gene
      network studies. In this article, we present an overview and comparison of recent
      developments of dynamic modeling and network approaches for time-course omics
      data, and their applications to various biological systems, health conditions and
      disease statuses. Moreover, various data reduction and analytical schemes ranging
      from mathematical to computational to statistical methods are compared including
      their merits, drawbacks and limitations. The most recent software, associated web
      resources and other potentials for the compared methods are also presented and
      discussed in detail.

PMID- 28430855
TI  - Cancer immunotherapy trial registrations increase exponentially but chronic
      immunosuppressive glucocorticoid therapy may compromise outcomes.

PMID- 28430856
TI  - A comprehensive analysis of rare genetic variation in amyotrophic lateral
      sclerosis in the UK.
AB  - Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor
      neurons. About 25 genes have been verified as relevant to the disease process,
      with rare and common variation implicated. We used next generation sequencing and
      repeat sizing to comprehensively assay genetic variation in a panel of known
      amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls.
      About 10% of patients were predicted to carry a pathological expansion of the
      C9orf72 gene. We found an increased burden of rare variants in patients within
      the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP,
      FUS, VCP, OPTN and UBQLN2. We found 11 patients (1%) carried more than one
      pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic
      lateral sclerosis. These findings show that the genetic architecture of
      amyotrophic lateral sclerosis is complex and that variation in the regulatory
      regions of associated genes may be important in disease pathogenesis.

PMID- 28430857
TI  - Repurposed drugs targeting eIF2&alpha;-P-mediated translational repression
      prevent neurodegeneration in mice.
AB  - See Mercado and Hetz (doi:10.1093/brain/awx107) for a scientific commentary on
      this article.Signalling through the PERK/eIF2&alpha;-P branch of the unfolded
      protein response plays a critical role in controlling protein synthesis rates in
      cells. This pathway is overactivated in brains of patients with Alzheimer&rsquo;s
      disease and related disorders and has recently emerged as a promising therapeutic
      target for these currently untreatable conditions. Thus, in mouse models of
      neurodegenerative disease, prolonged overactivation of PERK/eIF2&alpha;-P
      signalling causes sustained attenuation of protein synthesis, leading to memory
      impairment and neuronal loss. Re-establishing translation rates by inhibition of
      eIF2&alpha;-P activity, genetically or pharmacologically, restores memory and
      prevents neurodegeneration and extends survival. However, the experimental
      compounds used preclinically are unsuitable for use in humans, due to associated
      toxicity or poor pharmacokinetic properties. To discover compounds that have anti
      eIF2&alpha;-P activity suitable for clinical use, we performed phenotypic screens
      on a NINDS small molecule library of 1040 drugs. We identified two compounds,
      trazodone hydrochloride and dibenzoylmethane, which reversed eIF2&alpha;-P
      mediated translational attenuation in vitro and in vivo. Both drugs were markedly
      neuroprotective in two mouse models of neurodegeneration, using clinically
      relevant doses over a prolonged period of time, without systemic toxicity. Thus,
      in prion-diseased mice, both trazodone and dibenzoylmethane treatment restored
      memory deficits, abrogated development of neurological signs, prevented
      neurodegeneration and significantly prolonged survival. In tauopathy
      frontotemporal dementia mice, both drugs were neuroprotective, rescued memory
      deficits and reduced hippocampal atrophy. Further, trazodone reduced p-tau
      burden. These compounds therefore represent potential new disease-modifying
      treatments for dementia. Trazodone in particular, a licensed drug, should now be
      tested in clinical trials in patients.

PMID- 28430859
TI  - Blood Pressure in Acute Intracerebral Hemorrhage: Have We Been Looking in the
      Wrong Direction?

PMID- 28430858
TI  - Mapping genes for calcium signaling and their associated human genetic disorders.
AB  - Motivation: Signal transduction via calcium ions (Ca2+) represents a fundamental
      signaling pathway in all eukaryotic cells. A large portion of the human genome
      encodes proteins used to assemble signaling systems that can transduce signals
      with diverse spatial and temporal dynamics. Results: Here, we provide a map of
      all of the genes involved in Ca2+ signaling and link these genes to human genetic
      disorders. Using Gene Ontology terms and genome databases, 1805 genes were
      identified as regulators or targets of intracellular Ca2+ signals. Associating
      these 1805 genes with human genetic disorders uncovered 1470 diseases with
      mutated 'Ca2+ genes'. A network with scale-free properties appeared when the Ca2+
      genes were mapped to their associated genetic disorders. Availability and
      Implementation: The Ca2+ genome database is freely available at
      http://cagedb.uhlenlab.org and will foster studies of gene functions and genetic
      disorders associated with Ca2+ signaling. Contact: per.uhlen@ki.se. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28430860
TI  - Increased brainstem perfusion, but no blood-brain barrier disruption, during
      attacks of migraine with aura.
AB  - See Moskowitz (doi:10.1093/brain/awx099) for a scientific commentary on this
      article.The migraine aura is characterized by transient focal cortical
      disturbances causing dramatic neurological symptoms that are usually followed by
      migraine headache. It is currently not understood how the aura symptoms are
      related to the headache phase of migraine. Animal studies suggest that cortical
      spreading depression, the likely mechanism of migraine aura, causes disruption of
      the blood-brain barrier and noxious stimulation of trigeminal afferents leading
      to activation of brainstem nuclei and triggering of migraine headache. We used
      the sensitive and validated technique of dynamic contrast-enhanced high-field
      magnetic resonance imaging to simultaneously investigate blood-brain barrier
      permeability and tissue perfusion in the brainstem (at the level of the lower
      pons), visual cortex, and brain areas of the anterior, middle and posterior
      circulation during spontaneous attacks of migraine with aura. Patients reported
      to our institution to undergo magnetic resonance imaging during the headache
      phase after presenting with typical visual aura. Nineteen patients were scanned
      during attacks and on an attack-free day. The mean time from attack onset to
      scanning was 7.6 h. We found increased brainstem perfusion bilaterally during
      migraine with aura attacks. Perfusion also increased in the visual cortex and
      posterior white matter following migraine aura. We found no increase in blood
      brain barrier permeability in any of the investigated regions. There was no
      correlation between blood-brain barrier permeability, brain perfusion, and time
      from symptom onset to examination or pain intensity. Our findings demonstrate
      hyperperfusion in brainstem during the headache phase of migraine with aura,
      while the blood-brain barrier remains intact during attacks of migraine with
      aura. These data thus contradict the preclinical hypothesis of cortical spreading
      depression-induced blood-brain barrier disruption as a possible mechanism linking
      aura and headache.awx089media15422686892001.

PMID- 28430861
TI  - Reply to the letter to the editor 'Addressing the quality of the ESMO-MCBS' by
      Del Paggio.

PMID- 28430863
TI  - FGFR2 amplification in metastatic hormone-positive breast cancer and response to
      an mTOR inhibitor.

PMID- 28430862
TI  - How health-related quality of life assessment should be used in advanced
      colorectal cancer clinical trials.
AB  - Traditionally, the efficacy of cancer treatment in patients with advance or
      metastatic disease in clinical studies has been studied using overall survival
      and more recently tumor-based end points such as progression-free survival,
      measurements of response to treatment. However, these seem not to be the relevant
      clinical end points in current situation if such end points were no validated as
      surrogate of overall survival to demonstrate the clinical efficacy. Appropriate,
      meaningful, primary patient-oriented and patient-reported end points that
      adequately measure the effects of new therapeutic interventions are then crucial
      for the advancement of clinical research in metastatic colorectal cancer to
      complement the results of tumor-based end points. Health-related quality of life
      (HRQoL) is effectively an evaluation of quality of life and its relationship with
      health over time. HRQoL includes the patient report at least of the way a disease
      or its treatment affects its physical, emotional and social well-being. Over the
      past few years, several phase III trials in a variety of solid cancers have
      assessed the incremental value of HRQoL in addition to the traditional end points
      of tumor response and survival results. HRQoL could provide not only
      complementary clinical data to the primary outcomes, but also more precise
      predictive and prognostic value. This end point is useful for both clinicians and
      patients in order to achieve the dogma of precision medicine. The present article
      examines the use of HRQoL in phase III metastatic colorectal cancer clinical
      trials, outlines the importance of HRQoL assessment methods, analysis, and
      results presentation. Moreover, it discusses the relevance of including HRQoL as
      a primary/co-primary end point to support the progression-free survival results
      and to assess efficacy of treatment in the advanced disease setting.

PMID- 28430864
TI  - The gonadotropin-inhibitory hormone (Lpxrfa) system's regulation of reproduction
      in the brain-pituitary axis of the zebrafish (Danio rerio).
AB  - Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability
      to reduce gonadotropin expression/secretion in the pituitary. There have been few
      studies on GNIH orthologs in teleosts (LPXRFamide (Lpxrfa) peptides), which have
      provided inconsistent results. Therefore, the goal of this study was to determine
      the roles and modes of action by which Lpxrfa exerts its functions in the brain
      pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the
      ventral hypothalamus, with fibers extending throughout the brain and to the
      pituitary. In the preoptic area, Lpxrfa fibers interact with gonadotropin
      releasing hormone 3 (Gnrh3) soma. In pituitary explants, zebrafish peptide Lpxrfa
      3 downregulated luteinizing hormone beta subunit and common alpha subunit
      expression. In addition, Lpxrfa-3 reduced gnrh3 expression in brain slices,
      offering another pathway for Lpxrfa to exert its effects on reproduction.
      Receptor activation studies, in a heterologous cell-based system, revealed that
      all three zebrafish Lpxrfa peptides activate Lpxrf-R2 and Lpxrf-R3 via the
      PKA/cAMP pathway. Receptor activation studies demonstrated that, in addition to
      activating Lpxrf receptors, zebrafish Lpxrfa-2 and Lpxrfa-3 antagonize Kisspeptin
      2 (Kiss2) activation of Kisspeptin receptor-1a (Kiss1ra). The fact that kiss1ra
      expressing neurons in the preoptic area are innervated by Lpxrfa-ir fibers
      suggests an additional pathway for Lpxrfa action. Therefore, our results suggest
      that Lpxrfa may act as a reproductive inhibitory neuropeptide in the zebrafish
      that interacts with Gnrh3 neurons in the brain and with gonadotropes in the
      pituitary, while also potentially utilizing the Kiss2/Kiss1ra pathway.

PMID- 28430866
TI  - Maternal high-sucrose diets altered vascular large-conductance Ca2+-activated K+
      channels via reactive oxygen species in offspring rats.
AB  - Overnutrition during pregnancy could increase risks of cardiovascular diseases in
      late life. This study investigated whether and how reactive oxygen species (ROS)
      may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in
      the offspring exposed to prenatal high sucrose (HS). We found that prenatal HS
      diets significantly increased phenylephrine (PE)-induced vessel contractions in
      mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa
      blocker, IBTX) significantly increased PE-mediated vascular contractions in the
      control, not in the HS group. Electrophysiological studies demonstrated that BKCa
      current density and single-channel current were reduced in the vascular smooth
      muscle cells (VSMCs) of the HS offspring. The expression of BKCa alpha, beta1
      subunits in mesenteric arteries was decreased in the HS offspring, indicating
      that both activity and number of BKCa channels in HS offspring were reduced.
      Superoxide production and NADPH oxidase (NOX)4 of the HS offspring were elevated.
      Following inhibiting NOX by apocynin, vasoconstriction in the HS offspring was
      weakened and the reduced currents in the VSMCs were improved with altered protein
      kinase B (AKT) pathway. The results suggested that NOX4-derived ROS might inhibit
      the offspring vascular BKCa channel activity via AKT pathway.

PMID- 28430865
TI  - Unmet needs in the first-line treatment of follicular lymphoma.
AB  - For the majority of patients with newly diagnosed follicular lymphoma (FL),
      current treatments, while not curative, allow for long remission durations.
      However, several important needs remain unaddressed. Studies have consistently
      shown that ~20% of patients with FL experience disease progression within 2 years
      of first-line treatment, and consequently have a 50% risk of death in 5 years.
      Better characterization of this group of patients at diagnosis may provide
      insight into those in need of alternate or intensive therapies, facilitate a
      precision approach to inform clinical trials, and allow for improved patient
      counseling. Prognostic methods to date have employed clinical parameters, genomic
      methods, and a wide assortment of biological and biochemical markers, but none so
      far has been able to adequately identify this high-risk population. Advances in
      the first-line treatment of FL with chemoimmunotherapy have led to a median
      progression-free survival (PFS) of approximately 7 years; creating a challenge in
      the development of clinical trials where PFS is a primary end point. A surrogate
      end point that accurately predicts PFS would allow for new treatments to reach
      patients with FL sooner, or lessen toxicity, time, and expense to those patients
      requiring little to no therapy. Quality of response to treatment may predict PFS
      and overall survival in FL; as such complete response rates, either alone or in
      conjunction with PET imaging or minimal residual disease negativity, are being
      studied as surrogates, with complete response at 30 months after induction
      providing the strongest surrogacy evidence to date. A better understanding of how
      to optimize quality of life in the context of this chronic illness is another
      important focus deserving of further study. Ongoing efforts to address these
      important unmet needs are herein discussed.

PMID- 28430868
TI  - MOST-visualization: software for producing automated textbook-style maps of
      genome-scale metabolic networks.
AB  - Summary: Visualization of metabolites, reactions and pathways in genome-scale
      metabolic networks (GEMs) can assist in understanding cellular metabolism. Three
      attributes are desirable in software used for visualizing GEMs: (i) automation,
      since GEMs can be quite large; (ii) production of understandable maps that
      provide ease in identification of pathways, reactions and metabolites; and (iii)
      visualization of the entire network to show how pathways are interconnected. No
      software currently exists for visualizing GEMs that satisfies all three
      characteristics, but MOST-Visualization, an extension of the software package
      MOST (Metabolic Optimization and Simulation Tool), satisfies (i), and by using a
      pre-drawn overview map of metabolism based on the Roche map satisfies (ii) and
      comes close to satisfying (iii). Availability and Implementation: MOST is
      distributed for free on the GNU General Public License. The software and full
      documentation are available at http://most.ccib.rutgers.edu/. Contact:
      dslun@rutgers.edu. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 28430867
TI  - Emerging evidence for the role of differential tumor microenvironment in breast
      cancer racial disparity: a closer look at the surroundings.
AB  - Although increased awareness leading to early detection and prevention, as well
      as advancements in treatment strategies, have resulted in superior clinical
      outcomes, African American women with breast cancer continue to have greater
      mortality rates, compared to Caucasian American counterparts. Moreover, African
      American women are more likely to have breast cancer at a younger age and be
      diagnosed with aggressive tumor sub-types. Such racial disparities can be
      attributed to socioeconomic differences, but it is increasingly being recognized
      that these disparities may indeed be due to certain genetic and other non-genetic
      biological differences. Tumor microenvironment, which provides a favorable niche
      for the growth of tumor cells, is comprised of several types of stromal cells and
      the various proteins secreted as a consequence of bi-directional tumor-stromal
      cross-talk. Emerging evidence suggests inherent biological differences in the
      tumor microenvironment of breast cancer patients from different racial
      backgrounds. Tumor microenvironment components, affected by the genetic make-up
      of the tumor cells as well as other non-tumor-associated factors, may also render
      patients more susceptible to the development of aggressive tumors and faster
      progression of disease resulting in early onset, thus adversely affecting
      patients' survival. This review provides an overview of breast cancer racial
      disparity and discusses the existence of race-associated differential tumor
      microenvironment and its underlying genetic and non-genetic causal factors. A
      better understanding of these aspects would help further research on effective
      cancer management and improved approaches for reducing the racial disparities
      gaps in breast cancer patients.

PMID- 28430870
TI  - Potential mechanisms of white matter injury in the acute phase of experimental
      subarachnoid haemorrhage.

PMID- 28430869
TI  - Inhibition of the P2X7-PANX1 complex suppresses spreading depolarization and
      neuroinflammation.
AB  - Spreading depolarization is a wave of neuronal and glial depolarization. Within
      minutes after spreading depolarization, the neuronal hemichannel pannexin 1
      (PANX1) opens and forms a pore complex with the ligand-gated cation channel P2X7,
      allowing the release of excitatory neurotransmitters to sustain spreading
      depolarization and activate neuroinflammation. Here, we explore the hypothesis
      that the P2X7-PANX1 pore complex is a critical determinant of spreading
      depolarization susceptibility with important consequences for neuroinflammation
      and trigeminovascular activation. We found that genetic loss of function or
      ablation of the P2x7 gene inhibits spreading depolarization. Moreover,
      pharmacological suppression of the P2X7-PANX1 pore complex inhibits spreading
      depolarization in mice carrying the human familial hemiplegic migraine type 1
      R192Q missense mutation as well as in wild-type mice and rats. Pore inhibitors
      elevate the electrical threshold for spreading depolarization, and reduce
      spreading depolarization frequency and amplitude. Pore inhibitors also suppress
      downstream consequences of spreading depolarization such as upregulation of
      interleukin-1 beta, inducible nitric oxide synthase and cyclooxygenase-2 in the
      cortex after spreading depolarization. In addition, they inhibit surrogates for
      trigeminovascular activation, including expression of calcitonin gene-related
      peptide in the trigeminal ganglion and c-Fos in the trigeminal nucleus caudalis.
      Our results are consistent with the hypothesis that the P2X7-PANX1 pore complex
      is a critical determinant of spreading depolarization susceptibility and its
      downstream consequences, of potential relevance to its signature disorders such
      as migraine.

PMID- 28430871
TI  - ClusPro PeptiDock: efficient global docking of peptide recognition motifs using
      FFT.
AB  - Summary: We present an approach for the efficient docking of peptide motifs to
      their free receptor structures. Using a motif based search, we can retrieve
      structural fragments from the Protein Data Bank (PDB) that are very similar to
      the peptide's final, bound conformation. We use a Fast Fourier Transform (FFT)
      based docking method to quickly perform global rigid body docking of these
      fragments to the receptor. According to CAPRI peptide docking criteria, an
      acceptable conformation can often be found among the top-ranking predictions.
      Availability and Implementation: The method is available as part of the protein
      protein docking server ClusPro at https://peptidock.cluspro.org/nousername.php.
      Contact: midas@laufercenter.org or oraf@ekmd.huji.ac.il. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28430872
TI  - Optimal screening schedules for disease progression with application to diabetic
      retinopathy.
AB  - Clinical management of chronic diseases requires periodic evaluations. Subjects
      transition between various levels of severity of a disease over time, one of
      which may trigger an intervention that requires treatment. For example, in
      diabetic retinopathy, patients with type 1 diabetes are evaluated yearly for
      either the onset of proliferative diabetic retinopathy (PDR) or clinically
      significant macular edema (CSME) that would require immediate treatment to
      preserve vision. Herein, we investigate methods for the selection of personalized
      cost-effective screening schedules and compare them with a fixed visit schedule
      (e.g., annually) in terms of both cost and performance. The approach is
      illustrated using the progression of retinopathy in the DCCT/EDIC study.

PMID- 28430873
TI  - Bioinformatics in Germany: toward a national-level infrastructure.
AB  - The German Network for Bioinformatics Infrastructure (de.NBI) is a national
      initiative funded by the German Federal Ministry of Education and Research
      (BMBF). The mission of de.NBI is (i) to provide high-quality bioinformatics
      services to users in basic and applied life sciences research from academia,
      industry and biomedicine; (ii) to offer bioinformatics training to users in
      Germany and Europe through a wide range of workshops and courses; and (iii) to
      foster the cooperation of the German bioinformatics community with international
      network structures such as the European life-sciences Infrastructure for
      biological Information (ELIXIR). The network was launched by the BMBF in March
      2015 and now includes 40 service projects operated by 30 project partners that
      are organized in eight service centers. The de.NBI staff develops further and
      maintains almost 100 bioinformatics services for the human, plant and microbial
      research fields and provides comprehensive training courses to support users with
      different expertise levels in bioinformatics. In the future, de.NBI will expand
      its activities to the European level, as the de.NBI consortium was assigned by
      the BMBF to establish and run the German node of ELIXIR.

PMID- 28430875
TI  - Progressive atrophy of the globus pallidus (primary atrophy of the pallidal
      system). A system disease of the paralysis agitans type, characterized by atrophy
      of the motor cells of the corpus striatum. A contribution to the function of the
      corpus striatum. By J. Ramsay Hunt MD, New York. Brain 1917; 40: 58-148.

PMID- 28430874
TI  - Developmental SALL2 transcription factor: a new player in cancer.
AB  - SALL2, also known as Spalt-like transcription factor 2, is a member of the SALL
      family of transcription factors involved in development and conserved through
      evolution. Since its identification in 1996, findings indicate that SALL2 plays a
      role in neurogenesis, neuronal differentiation and eye development. Consistently,
      SALL2 deficiency associates with neural tube defects and coloboma, a congenital
      eye disease. Relevant to cancer, clinical studies indicate that SALL2 is
      deregulated in various cancers and is a specific biomarker for Synovial Sarcoma.
      However, the significance of SALL2 deregulation in this disease is controversial.
      Here, we present and discuss all available information about SALL2 since its
      discovery, including isoforms, regulation, targets and functions. We specifically
      discuss the role of SALL2 in the regulation of cell proliferation and survival
      within the context of the identified target genes, its interaction with viral
      oncogenes, and its association with the TP53 tumor suppressor and MYC oncogene.
      Special attention is given to p53-independent SALL2 regulation of pro-apoptotic
      genes BAX and PMAIP1, and the implication of these findings on the apoptotic
      response of cancer cells to therapy. Understanding SALL2 function and the
      molecular mechanisms governing its expression and activity is critical to
      comprehend why and how SALL2 could contribute to disease. This knowledge will
      open new perspectives for the development of molecular targeted approaches in
      disease.

PMID- 28430876
TI  - IFT25, an intraflagellar transporter protein dispensable for ciliogenesis in
      somatic cells, is essential for sperm flagella formation.
AB  - Intraflagellar transport (IFT) is a conserved mechanism essential for the
      assembly and maintenance of most eukaryotic cilia and flagella. However, IFT25, a
      component of the IFT complex, is not required for the formation of cilia in
      somatic tissues. In mice, the gene is highly expressed in the testis, and its
      expression is upregulated during the final phase when sperm flagella are formed.
      To investigate the role of IFT25 in sperm flagella formation, the gene was
      specifically disrupted in male germ cells. All homozygous knockout mice survived
      to adulthood and did not show any gross abnormalities. However, all homozygous
      knockout males were completely infertile. Sperm numbers were reduced and these
      sperm were completely immotile. Multiple morphological abnormalities were
      observed in sperm, including round heads, short and bent tails, with some tails
      showing branched flagella and others with frequent abnormal thicknesses, as well
      as swollen tips of the tail. Transmission electron microscopy revealed that
      flagellar accessory structures, including the fibrous sheath and outer dense
      fibers, were disorganized, and most sperm had also lost the "9+2" microtubule
      structure. In the testis, IFT25 forms a complex with other IFT proteins. In Ift25
      knockout testes, IFT27, an IFT25 binding partner, was missing, and IFT20 and
      IFT81 levels were also reduced. Our findings suggest that IFT25, although not
      necessary for the formation of cilia in somatic cells, is indispensable for sperm
      flagellum formation and male fertility in mice.

PMID- 28430877
TI  - The accessible chromatin landscape during conversion of human embryonic stem
      cells to trophoblast by bone morphogenetic protein 4.
AB  - Human embryonic stem cells (hESCs) exposed to the growth factor bone
      morphogenetic protein 4 (BMP4) in the absence of FGF2 have been used as a model
      to study the development of placental development. However, little is known about
      the cis-regulatory mechanisms underlying this important process. In this study,
      we used the public available chromatin accessibility data of hESC H1 cells and
      BMP4-induced trophoblast (TB) cell lines to identify DNase I hypersensitive sites
      (DHSs) in the two cell lines, as well as the transcription factor (TF) binding
      sites within the DHSs. By comparing read profiles in H1 and TB, we identified 17
      472 TB-specific DHSs. The TB-specific DHSs are enriched in terms of "blood
      vessel" and "trophectoderm," consisting of TF motifs family: Leucine Zipper,
      Helix-Loop-Helix, GATA, and ETS. To validate differential expression of the TFs
      binding to these motifs, we analyzed public available RNA-seq and microarray data
      in the same context. Finally, by integrating the protein-protein interaction
      data, we constructed a TF network for placenta development and identified top 20
      key TFs through centrality analysis in the network. Our results indicate BMP4
      induced TB system provided an invaluable model for the study of TB development
      and highlighted novel candidate genes in placenta development in human.

PMID- 28430878
TI  - Cosmetic Liposuction: Preoperative Risk Factors, Major Complication Rates, and
      Safety of Combined Procedures.
AB  - Background: Liposuction is among the most commonly performed aesthetic
      procedures, and is being performed increasingly as an adjunct to other
      procedures. Objectives: To report the incidence and risk factors of significant
      complications after liposuction, and to determine whether adding liposuction to
      other cosmetic surgical procedures impacts the complication risk. Methods: A
      prospective cohort of patients who underwent liposuction between 2008 and 2013
      was identified from the CosmetAssure database. Primary outcome was occurrence of
      major complications requiring emergency room visit, hospital admission, or
      reoperation within 30 days of the operation. Univariate and multivariate analysis
      evaluated risk factors including age, gender, body mass index (BMI), smoking,
      diabetes, type of surgical facility, and combined procedures. Results: Of the
      31,010 liposuction procedures, only 11,490 (37.1%) were performed as a solitary
      procedure. Liposuction alone had a major complication rate of 0.7% with hematoma
      (0.15%), pulmonary complications (0.1%), infection (0.1%), and confirmed venous
      thromboembolism (VTE) (0.06%) being the most common. Independent predictors of
      major complications included combined procedures (Relative Risk (RR) 4.81), age
      (RR 1.01), BMI (RR 1.05), and procedures performed in hospitals (RR 1.36). When
      examining specifically other aesthetic procedures performed alone or with
      liposuction, combined procedures had a higher risk of confirmed VTE (RR 5.65),
      pulmonary complications (RR 2.72), and infection (RR 2.41), but paradoxically
      lower hematoma risk (RR 0.77) than solitary procedures. Conclusions: Liposuction
      performed alone is a safe procedure with a low risk of major complications.
      Combined procedures, especially on obese or older individuals, can significantly
      increase complication rates. The impact of liposuction on the risk of hematoma in
      combined procedures needs further investigation. Level of Evidence 2: 

PMID- 28430879
TI  - Role of phosphatase and tensin homolog in hypoxic pulmonary vasoconstriction.
AB  - Aims: Hypoxic pulmonary vasoconstriction (HPV) redistributes blood flow from
      poorly ventilated to better aerated areas in the lung, thereby optimizing
      ventilation-perfusion ratio (V/Q). Pulmonary artery smooth muscle cell (PASMC)
      contraction in response to hypoxia is triggered by Ca2+ influx via transient
      receptor potential canonical 6 (TRPC6) cation channels that have translocated to
      caveolae in the plasma membrane. Since phosphatase and tensin homolog (PTEN) was
      suggested to regulate TRPC6 in endothelial cells, we aimed to define its role in
      the hypoxic response of PASMCs and as a putative mediator of HPV. Methods and
      results: In isolated perfused mouse lungs, smooth muscle specific PTEN deficiency
      attenuated pulmonary vasoconstriction in response to hypoxia but not to
      angiotensin II (Ang II). Analogously, siRNA-mediated knock down of PTEN in human
      PASMC inhibited the hypoxia-induced increase in cytosolic Ca2+ concentration
      ([Ca2+]i). Co-immunoprecipitation and proximity ligation assays revealed
      increased interaction of PTEN with TRPC6 in human PASMC and murine lungs in
      response to hypoxia. In hypoxic PASMC, both PTEN and TRPC6 translocated to
      caveolae, and this response was blocked by pharmacological inhibition of Rho
      associated protein kinase (ROCK) which in parallel prevented PTEN-TRPC6
      interaction, hypoxia-induced [Ca2+]i increase, and HPV in PASMC and murine lungs,
      respectively. Conclusion: Our data indicate a novel interplay between ROCK and
      [Ca2+]i signalling in HPV via PTEN, in that ROCK mediates interaction of PTEN and
      TRPC6 which then conjointly translocate to caveolae allowing for Ca2+ influx into
      and subsequent contraction of PASMC.

PMID- 28430880
TI  - Cerebral Abscess Associated With Odontogenic Bacteremias, Hypoxemia, and Iron
      Loading in Immunocompetent Patients With Right-to-Left Shunting Through Pulmonary
      Arteriovenous Malformations.
AB  - Background: Cerebral abscess is a recognized complication of pulmonary
      arteriovenous malformations (PAVMs) that allow systemic venous blood to bypass
      the pulmonary capillary bed through anatomic right-to-left shunts. Broader
      implications and mechanisms remain poorly explored. Methods: Between June 2005
      and December 2016, at a single institution, 445 consecutive adult patients with
      computed tomography-confirmed PAVMs (including 403 [90.5%] with hereditary
      hemorrhagic telangiectasia) were recruited to a prospective series. Multivariate
      logistic regression was performed and detailed periabscess histories were
      evaluated to identify potential associations with cerebral abscess. Rates were
      compared to an earlier nonoverlapping series. Results: Thirty-seven of the 445
      (8.3%) patients experienced a cerebral abscess at a median age of 50 years
      (range, 19-76 years). The rate adjusted for ascertainment bias was 27 of 435
      (6.2%). Twenty-nine of 37 (78.4%) patients with abscess had no PAVM diagnosis
      prior to their abscess, a rate unchanged from earlier UK series. Twenty-one of 37
      (56.7%) suffered residual neurological deficits (most commonly memory/cognition
      impairment), hemiparesis, and visual defects. Isolation of periodontal microbes,
      and precipitating dental and other interventional events, emphasized potential
      sources of endovascular inoculations. In multivariate logistic regression,
      cerebral abscess was associated with low oxygen saturation (indicating greater
      right-to-left shunting); higher transferrin iron saturation index; intravenous
      iron use for anemia (adjusted odds ratio, 5.4 [95% confidence interval, 1.4
      21.1]); male sex; and venous thromboemboli. There were no relationships with
      anatomic attributes of PAVMs, or red cell indices often increased due to
      secondary polycythemia. Conclusions: Greater appreciation of the risk of cerebral
      abscess in undiagnosed PAVMs is required. Lower oxygen saturation and intravenous
      iron may be modifiable risk factors.

PMID- 28430881
TI  - Stroke in the young.

PMID- 28430882
TI  - Inhibition of the cardiac myocyte mineralocorticoid receptor ameliorates
      doxorubicin-induced cardiotoxicity.
AB  - Aim: Anthracyclines such as doxorubicin are widely used in cancer therapy but
      their use is limited by cardiotoxicity. Up to date there is no established
      strategy for the prevention of anthracyclin-induced heart failure. In this study,
      we evaluated the role of the cardiac myocyte mineralocorticoid receptor (MR)
      during doxorubicin-induced cardiotoxicity. Methods and results: A single high
      dose or repetitive low-dose doxorubicin administration lead to markedly reduced
      left ventricular function in mice. Treatment with the MR antagonist eplerenone
      prevented doxorubicin-induced left ventricular dysfunction. In order to identify
      the cell types and molecular mechanisms involved in this beneficial effect we
      used a mouse model with cell type-specific MR deletion in cardiac myocytes.
      Cardiac myocyte MR deletion largely reproduced the effect of pharmacological MR
      inhibition on doxorubicin-induced cardiotoxicity. RNAseq from isolated cardiac
      myocytes revealed a repressive effect of doxorubicin on gene expression which was
      prevented by MR deletion. Conclusions: We show here that (i) eplerenone prevents
      doxorubicin-induced left ventricular dysfunction in mice, and (ii) this
      beneficial effect is related to inhibition of MR in cardiac myocytes. Together
      with present clinical trial data our findings suggest that MR antagonism may be
      appropriate for the prevention of doxorubicin-induced cardiotoxicity.

PMID- 28430883
TI  - Ten-year results of aortic valve replacement with first-generation Mitroflow
      bioprosthesis: is early degeneration a structural or a technical issue?
AB  - OBJECTIVES: Concerns have been raised about the durability of the first
      generation Mitroflow aortic bioprosthesis (model 12 A-LX) due to the lack of
      anticalcification treatment. This study reflects a 10-year experience with this
      prosthesis for aortic valve replacement. METHODS: From June 2003 to May 2012, the
      Mitroflow prosthesis was used for aortic valve replacement in 510 patients, of
      whom only 467 with complete clinical follow-up were included for analysis. Study
      end-points were survival and incidence of structural valve degeneration (SVD).
      Analysis of SVD was based on cumulative incidence function and competing-risk Cox
      regression. RESULTS: The mean patient age was 76.4 +/- 6.1 years. Valve sizes
      from 23 to 25 were used in 70.4%, whereas sizes from 19 to 21 were used in only
      19.2%, thereby avoiding patient-prosthesis mismatch in 89.1%. Within a median
      follow-up time of 6.6 years (interquartile range 4.4), a cumulative 2375 patient
      years, the survival rate was 86.2%, 67.3% and 33.3% at 1, 5 and 10 years,
      respectively. The cumulative incidence of SVD, with death as a competing risk,
      was 0%, 0.7% and 6.2% at 1, 5 and 10 years, respectively. Only age <75 years
      tended to affect the late hazard of SVD (hazard ratio 0.50, 95% confidence
      interval 0.23-1.08, P  = 0.08), regardless of valve-specific issues. CONCLUSIONS:
      The data do not support the concerns about early accelerated structural
      degeneration of the first-generation Mitroflow bioprosthesis used for aortic
      valve replacement in patients older than 75 years. We postulate that limiting the
      number of small prostheses using a proper implantation technique has enhanced the
      reduction in risk of significant patient-prosthesis mismatch as the main
      determinant of early SVD.

PMID- 28430884
TI  - A 20-Year Temporal Change Analysis in Incidence, Presenting Phenotype and
      Mortality, in the Dutch IBDSL Cohort-Can Diagnostic Factors Explain the Increase
      in IBD Incidence?
AB  - Background: The aim was to study temporal changes in incidence, disease phenotype
      at diagnosis, and mortality of adult inflammatory bowel disease [IBD] patients in
      South Limburg, The Netherlands, diagnosed between 1991 and 2010. In addition, the
      2010 IBD prevalence was estimated. Methods: A multi-faceted approach including
      hospital administrations, the national pathology registry [PALGA], and general
      practitioners led to the identification of 1162 patients with Crohn's disease
      [CD], 1663 with ulcerative colitis [UC], and 84 with unclassified IBD [IBD-U].
      Temporal changes in incidence, disease phenotype, and mortality were studied
      using linear, multinomial regression analyses, and standardised mortality rates
      [SMR], respectively. Results: The annual incidences increased from 17.90/100000
      in 1991 to 40.36/100000 in 2010 for IBD, from 5.84/100000 to 17.49/100000 for CD,
      and from 11.67/100000 to 21.47/100000 for UC [p < 0.01 for all]. A shift towards
      milder disease at diagnosis was observed over time [eg decrease of complicated
      disease in CD, increase of proctitis in UC]. IBD mortality was similar to that in
      the general population (SMR 0.92; 95% confidence interval [CI] 0.81-1.05), and
      did not change over time. The estimated IBD prevalence was 830/100000.
      Conclusions: The IBD incidence in South Limburg increased significantly between
      1991 and 2010. The shift towards milder disease at diagnosis in parallel with the
      improved diagnostics and ability to detect low-grade inflammation was suggestive
      of an important role of diagnostic factors in this increase. Environmental
      factors probably played a role as well. The mortality was low and, together with
      the increasing incidence, led to the high prevalence of IBD in South Limburg.

PMID- 28430885
TI  - Lesion mapping of stroke-related erectile dysfunction.
AB  - Acute ischaemic stroke in brain areas contributing to male sexual function may
      impair erectile function depending on the lesion site. This study intended to
      determine associations between stroke-related erectile dysfunction and cerebral
      ischaemic lesion sites using voxel-based lesion mapping. In 52 males (mean age
      60.5 +/- 10.5 years) with first-ever ischaemic strokes, we assessed erectile
      function after and retrospectively 3 months prior to the stroke using scores of
      the 5-item International Index of Erectile Function-5 questionnaire. We assessed
      cardiovascular risk factors and determined clinical stroke severity and infarct
      volumes as well as total brain volume by neuroimaging. We calculated correlations
      between patient age, clinical stroke severity, infarct volumes as well as brain
      volumes and the difference between erectile dysfunction scores before and after
      stroke. Moreover, we compared patient age, prevalence of cardiovascular risk
      factors, clinical stroke severity, infarct volumes and brain volumes of patients
      with unchanged and deteriorated erectile function after stroke. The infarcts were
      manually outlined and transformed into stereotaxic space. We determined the
      lesion overlap and performed subtraction analyses of lesions. In a voxel-based
      lesion analysis, the difference between erectile dysfunction scores before and
      after stroke was correlated with the lesion site using t-test statistics.
      Finally, we conducted a region of interest-based multivariate linear regression
      analysis that was adjusted for potential confounding factors including patient
      age, clinical stroke severity, imaging modality, lesion size and brain volume. In
      32 patients (61.5%) erectile dysfunction scores declined after the stroke and
      therefore had stroke-related erectile dysfunction. Deterioration of erectile
      dysfunction scores was not associated with patient age, clinical stroke severity,
      infarct volume, brain volume, and cardiovascular risk factors. The voxel-wise
      subtraction analysis showed associations between stroke-related erectile
      dysfunction and lesion sites in the right occipito-parietal cortex and thalamus,
      as well as in the left insula and adjacent temporo-parietal areas. Using voxel
      wise t-test statistics, we showed associations between deterioration of erectile
      function and lesion sites in the right occipital and thalamic region, and the
      left parietal association area. The linear regression analysis showed that stroke
      related erectile dysfunction remained associated with lesions of the right
      occipital and left parietal association areas after adjusting for confounding
      factors. In conclusion, our voxel-wise analysis indicates that deteriorating
      erectile function after stroke is associated with lesions in the right occipito
      parietal and thalamic areas integrating visual and somatosensory information, as
      well as lesions in the left insular and adjacent parieto-temporal areas
      contributing to generating and mapping visceral arousal states.

PMID- 28430887
TI  - Measurement of forces and moments around the maxillary arch for treatment of a
      simulated lingual incisor and high canine malocclusion using straight and
      mushroom archwires in fixed lingual appliances.
AB  - Introduction: An Orthodontic SIMulator (OSIM) was used to investigate the
      propagation of forces and moments around a simulated archform for a gingival
      displaced canine and lingual displaced lateral incisor using fixed lingual
      orthodontic appliances. Methods: In-Ovation L self-ligating lingual brackets were
      bonded to anatomically shaped teeth on the OSIM, and the teeth were positioned
      such that a G4 NiTi 0.016" large maxillary mushroom archwire could be ligated in
      passive position. Each trial consisted of two movements: a 3mm lingual
      displacement of the 1-2 lateral incisor at 0.2 mm increments, and a 1.5 mm
      gingival displacement of the 2-3 canine at 0.15 mm increments (n = 50). Anterior
      brackets were repositioned to accommodate G4 NiTi 0.016" universal straight
      archwires (n = 50). Tests were completed at 37 degrees C, and force and moment
      data in all directions was collected for each tooth around the arch at all
      increments. Results: In general, the straight archwire produced significantly
      larger forces and moments at the centre of resistance for teeth of interest than
      did mushroom archwires. Specifically, the straight archwire produced 2.62 N and
      3.81 N more force in the direction of tooth movement on the tooth being moved for
      a gingival displaced canine and lingual displaced lateral incisor, respectively,
      as compared to mushroom archwires. Conclusions: Results from this study suggest
      that mushroom archwires may provide better mechanics for movement of teeth in the
      anterior segment when using a round archwire; however, only biomechanical data
      was considered in this study and there are many factors that need to be
      considered in treatment planning.

PMID- 28430886
TI  - Intrinsic protein disorder reduces small-scale gene duplicability.
AB  - Whereas the rate of gene duplication is relatively high, only certain
      duplications survive the filter of natural selection and can contribute to genome
      evolution. However, the reasons why certain genes can be retained after
      duplication whereas others cannot remain largely unknown. Many proteins contain
      intrinsically disordered regions (IDRs), whose structures fluctuate between
      alternative conformational states. Due to their high flexibility, IDRs often
      enable protein-protein interactions and are the target of post-translational
      modifications. Intrinsically disordered proteins (IDPs) have characteristics that
      might either stimulate or hamper the retention of their encoding genes after
      duplication. On the one hand, IDRs may enable functional diversification, thus
      promoting duplicate retention. On the other hand, increased IDP availability is
      expected to result in deleterious unspecific interactions. Here, we interrogate
      the proteomes of human, Drosophila melanogaster, Caenorhabditis elegans,
      Saccharomyces cerevisiae, Arabidopsis thaliana and Escherichia coli, in order to
      ascertain the impact of protein intrinsic disorder on gene duplicability. We show
      that, in general, proteins encoded by duplicated genes tend to be less disordered
      than those encoded by singletons. The only exception is proteins encoded by
      ohnologs, which tend to be more disordered than those encoded by singletons or
      genes resulting from small-scale duplications. Our results indicate that
      duplication of genes encoding IDPs outside the context of whole-genome
      duplication (WGD) is often deleterious, but that IDRs facilitate retention of
      duplicates in the context of WGD. We discuss the potential evolutionary
      implications of our results.

PMID- 28430888
TI  - QoL is a cool tool.

PMID- 28430889
TI  - Accuracy of Diagnostic Tests for Schistosoma mansoni Infection in Asymptomatic
      Eritrean Refugees: Serology and Point-of-Care Circulating Cathodic Antigen
      Against Stool Microscopy.
AB  - Background: The unprecedented increase in number of African refugees arriving in
      Europe is confronting clinicians and general practitioners with the question of
      whether or not and how to screen migrants from endemic regions for Schistosoma
      mansoni infection. Methods: We assessed the accuracy of 3 different diagnostic
      tests for S. mansoni infection (stool microscopy [samples prepared by
      sedimentation technique], serology, and point-of-care circulating cathodic
      antigen [POC-CCA] urine cassette test) in 107 newly arrived asymptomatic Eritrean
      refugees in Switzerland. Result: Sixty-three study participants (59%) tested
      positive by at least 1 of the 3 methods. Thirty-seven participants (35%) were
      considered to have active schistosomiasis, either due to the detection of
      parasite eggs in stool and/or the presence of a concordant positive serology and
      urine POC-CCA test, which we consider to be a suitable surrogate marker of active
      infection. Of 23 microscopy-positive participants, 22 were positive by serology
      (95.7% sensitivity) and 21 were positive by the urine POC-CCA test (91.3%
      sensitivity). The combination of serology and urine POC-CCA testing detected all
      23 microscopy-positive study participants (100% sensitivity). Conclusions: With a
      sensitivity of 100% (95% confidence interval, 82.2%-100%), the combination of
      serology plus urine POC-CCA testing appears to be the most sensitive screening
      option for asymptomatic S. mansoni infection in Eritrean refugees, compared with
      stool sedimentation microscopy.

PMID- 28430890
TI  - Acceptability comparison between Hawley retainers and vacuum-formed retainers in
      orthodontic adult patients: a single-centre, randomized controlled trial.
AB  - Background: Hawley retainers (HRs) and vacuum formed retainers (VFRs) are the
      most commonly used removable retainers in the orthodontic practice. Patients'
      cooperation in wearing these appliances is affected by the levels of discomfort
      and oral impairment. The evidence regarding their acceptably among orthodontic
      patients is limited. Aims: To compare the acceptability of HRs and VFRs over a 6
      month period in a group of fixed orthodontic patients. Trial Design: Two-arm
      parallel-group randomized controlled trial. Methods: Patients being treated at
      the Orthodontic Department of Saudi Swiss Consultant Dental Centre, Al-Khobar,
      Saudi Arabia, who met the inclusion criteria were invited to participate.
      Inclusion criteria were treatment only with fixed appliances, no lateral
      expansion treatment, no hypodontia, no cleft lip and palate, no surgical
      corrections, no extraction-based plans, 18 years old or greater, and willingness
      to wear maxillary and mandibular removable retainers. Participants were
      distributed randomly using concealed envelopes into two groups: HR group and VFR
      group. A pilot-tested questionnaire was filled at three times: 1 week after
      fitting of the retainer (T1), 3 months and 6 months following appliance fitting
      (T2 and T3, respectively). Ten questions were given on biting, fitting of the
      appliance, speech, appearance, oral hygiene, durability, gingival irritation,
      swallowing, self-confidence, and comfort. Responses were given on a visual
      analogue scale. Blinding was employed during data analysis. Results: Ninety-four
      patients were included primarily. Six patients in the Hawley group and two
      patients in the VFR group failed to complete the study. Therefore, 86 patients
      were included the analysis (HR group: 41; VFR group: 45). No significant
      differences were found between the two groups in biting, fitting of the
      appliance, and hygiene perception, whereas significant differences were detected
      in speech (P < 0.05), appearance (P < 0.001), gingival irritation (P < 0.001),
      durability (P < 0.001), swallowing (P < 0.001), self-confidence, and comfort (P <
      0.001). No harm to any patient was noticed during the trial. Conclusions: Over a
      6-month period of retention, VFR was significantly more acceptable than HR in
      speech, appearance, gingival irritation, swallowing, self-confidence, and
      comfort. Subjects in the HR group believed that their retainers were
      significantly more durable than those in the VFR group at the final assessment.
      Both retainers were equal regarding fitting of the appliance, biting, and hygiene
      perception. Registration: Not registered. Protocol: The protocol was not
      published before trial commencement. Funding: This trial was funded by the Saudi
      Swiss Consultant Dental Centre.

PMID- 28430891
TI  - Development and Validation of Diagnostic Criteria for IBD Subtypes Including IBD
      unclassified in Children: a Multicentre Study From the Pediatric IBD Porto Group
      of ESPGHAN.
AB  - Background: The revised Porto criteria identify subtypes of paediatric
      inflammatory bowel diseases: ulcerative colitis [UC], atypical UC, inflammatory
      bowel disease unclassified [IBDU], and Crohn's disease [CD]. Others have proposed
      another subclassifiction of Crohn's colitis. In continuation of the Porto
      criteria, we aimed to derive and validate criteria, termed "PIBD-classes," for
      standardising the classification of the different IBD subtypes. Methods: This was
      a multicentre retrospective longitudinal study from 23 centres affiliated with
      the Port -group of ESPGHAN. Both a hypothesis-driven judgmental approach and
      mathematical classification and regression tree [CART] modelling were used for
      creating a diagnostic algorithm. Since small bowel inflammation is easily
      recognised as CD, we focused here primarily on the phenotype of colitis. Results:
      In all, 749 IBD children were enrolled: 236 [32%] Crohn's colitis, 272 [36%] UC
      and 241 [32%] IBDU [age 10.9 +/- 3.6 years] with a median follow-up of 2.8 years
      (interquartile range [IQR] 1.7-4.3). A total of 23 features were clustered in
      three classes according to their prevalence in UC: six class-1 features [0%
      prevalence in UC], 12 class-2 features [< 5% prevalence], and five class-3
      features [5-10% prevalence]. According to the algorithm, the disease should be
      classified as UC if no features exist in any of the classes. When at least one
      feature exists, different combinations classify the disease into atypical UC,
      IBDU or CD. The algorithm differentiated UC from CD and IBDU with 80% sensitivity
      (95% confidence interval [CI] 71-88%) and 84% specificity [77-89%], and CD from
      IBDU and UC with 78% sensitivity [67-87%] and 94% specificity [89-97%].
      Conclusions: The validated PIBD-classes algorithm can adequately classify
      children with IBD into small bowel CD, colonic CD, IBDU, atypical UC, and UC.

PMID- 28430892
TI  - Anti-arrhythmic potential of the late sodium current inhibitor GS-458967 in
      murine Scn5a-1798insD+/- and human SCN5A-1795insD+/- iPSC-derived cardiomyocytes.
AB  - Aims: Selective inhibition of cardiac late sodium current (INaL) is an emerging
      target in the treatment of ventricular arrhythmias. We investigated the
      electrophysiological effects of GS-458967 (GS967), a potent, selective inhibitor
      of INaL, in an overlap syndrome model of both gain and loss of sodium channel
      function, comprising cardiomyocytes derived from both human SCN5A-1795insD+/-
      induced pluripotent stem cells (hiPSC-CMs) and mice carrying the homologous
      mutation Scn5a-1798insD+/-. Methods and results: On patch-clamp analysis, GS967
      (300 nmol/l) reduced INaL and action potential (AP) duration in isolated
      ventricular myocytes from wild type and Scn5a-1798insD+/- mice, as well as in
      SCN5A-1795insD+/- hiPSC-CMs. GS967 did not affect the amplitude of peak INa, but
      slowed its recovery, and caused a negative shift in voltage-dependence of INa
      inactivation. GS967 reduced AP upstroke velocity in Scn5a-1798insD+/- myocytes
      and SCN5A-1795insD+/- hiPSC-CMs. However, the same concentration of GS967 did not
      affect conduction velocity in Scn5a-1798insD+/- mouse isolated hearts, as
      assessed by epicardial mapping. GS967 decreased the amplitude of delayed after
      depolarizations and prevented triggered activity in mouse Scn5a-1798insD+/-
      cardiomyocytes. Conclusion: The INaL inhibitor GS967 decreases repolarization
      abnormalities and has anti-arrhythmic effects in the absence of deleterious
      effects on cardiac conduction. Thus, selective inhibition of INaL constitutes a
      promising pharmacological treatment of cardiac channelopathies associated with
      enhanced INaL. Our findings furthermore implement hiPSC-CMs as a valuable tool
      for assessment of novel pharmacological approaches in inherited sodium
      channelopathies.

PMID- 28430893
TI  - Congeneric Predaceous Diving Beetle Species Fail to Segregate in a Floodplain
      System: A Case of Amplified Sympatry.
AB  - Coexistence of closely related species has long been a focus of biologists in
      their efforts to explain mechanisms that drive community assembly. Dytiscidae
      (predaceous diving beetles) are a group that shows a particularly high affinity
      for sympatry despite their relatedness. Our objective was to investigate the
      degree of overlap among Neoporus (Guignot) species (Coleoptera: Dytiscidae) in
      floodplains of the southeastern United States. We sampled two floodplain habitats
      (permanent oxbow lakes and temporarily flooded pools) of the Altamaha River
      (Georgia, USA) for Neoporus species over three years. Six species of Neoporus
      were collected during our study, and a significant amount of overlap (spatial and
      temporal) was documented. Analysis suggested that none of the species exhibited a
      preference toward one habitat type or the other. Temporally, no striking patterns
      of segregation emerged. No negative correlations between species were documented,
      but neither were significant positive correlations found. This absence of
      distinct patterns suggests a lack of segregation among Neoporus species in
      floodplains of the Altamaha River. While Dytiscidae in general appears to be a
      particularly sympatric group of organisms, overlap among congeneric species
      within the family has been documented less frequently. Our study provides new
      insight into the degree to which dytiscids are capable of coexisting in space and
      time.

PMID- 28430894
TI  - Pooling and the Potential Dilution of Repeat Influenza Vaccination Effects.

PMID- 28430895
TI  - CORRIGENDUM.

PMID- 28430896
TI  - Evidence of secular trend in mandibular pubertal growth.
AB  - Background: During puberty, mandibular growth follows a growth curve comparable
      to somatic growth. This study aimed to review the relationship between mandibular
      pubertal peak height velocity (PHV) and skeletal age, and to investigate the
      possibility of a secular trend. Methods: Retrospective analysis was performed of
      two historical craniofacial growth studies (Denver Growth Study; observational
      time: 1943-1965, and Zurich Growth Study; observational time: 1982-1984) of
      healthy untreated subjects. Two mandibular growth measures (Articulare-Pogonion
      [Ar-Pg], Condylion-Pogonion [Co-Pg]) were retrieved from cephalograms (n: 990)
      and corresponding skeletal age based on hand-wrist radiographs. Mandibular growth
      velocity was related to skeletal age, PHV was established by use of cubic
      smoothing splines and variability was calculated by bootstrap resampling for
      every growth study and gender separately. Results: Sexual dimorphism in
      mandibular growth was apparent in both cohorts. In subjects of the Denver Growth
      Study, mandibular PHV occurred at a more advanced skeletal age than in subjects
      of the Zurich Growth Study. This trend was more pronounced in males, for whom PHV
      of Co-Pg shifted from 14.4 to 13.8 years and of Ar-Pg from 14.6 to 13.7 years.
      This tendency was more subtle in females: PHV of Co-Pg shifted from 12.7 to 12.4
      years and of Ar-Pg from 12.6 to 11.8 years. Conclusions: Mandibular growth
      appears to be subject to a secular trend. When related to skeletal age, this
      secular trend seems to be more accentuated than the established secular trend for
      somatic pubertal growth.

PMID- 28430897
TI  - Genetic variants associated with the root system architecture of oilseed rape
      (Brassica napus L.) under contrasting phosphate supply.
AB  - Breeding crops with ideal root system architecture for efficient absorption of
      phosphorus is an important strategy to reduce the use of phosphate fertilizers.
      To investigate genetic variants leading to changes in root system architecture,
      405 oilseed rape cultivars were genotyped with a 60K Brassica Infinium SNP array
      in low and high P environments. A total of 285 single-nucleotide polymorphisms
      were associated with root system architecture traits at varying phosphorus
      levels. Nine single-nucleotide polymorphisms corroborate a previous linkage
      analysis of root system architecture quantitative trait loci in the BnaTNDH
      population. One peak single-nucleotide polymorphism region on A3 was associated
      with all root system architecture traits and co-localized with a quantitative
      trait locus for primary root length at low phosphorus. Two more single-nucleotide
      polymorphism peaks on A5 for root dry weight at low phosphorus were detected in
      both growth systems and co-localized with a quantitative trait locus for the same
      trait. The candidate genes identified on A3 form a haplotype 'BnA3Hap', that will
      be important for understanding the phosphorus/root system interaction and for the
      incorporation into Brassica napus breeding programs.

PMID- 28430898
TI  - Plant Water Stress Affects Interactions Between an Invasive and a Naturalized
      Aphid Species on Cereal Crops.
AB  - In cereal cropping systems of the Pacific Northwestern United States (PNW),
      climate change is projected to increase the frequency of drought during summer
      months, which could increase water stress for crop plants. Yet, it remains
      uncertain how interactions between herbivore species are affected by drought
      stress. Here, interactions between two cereal aphids present in PNW cereal
      systems, Metopolophium festucae (Theobald) subsp. cerealium (a newly invasive
      species) and Rhopalosiphum padi L. (a naturalized species), were tested relative
      to wheat water stress. When aphids were confined in leaf cages on wheat,
      asymmetrical facilitation occurred; per capita fecundity of R. padi was increased
      by 46% when M. festucae cerealium was also present, compared to when only R. padi
      was present. Imposed water stress did not influence this interaction. When aphids
      were confined on whole wheat plants, asymmetrical competition occurred;
      cocolonization inhibited M. festucae cerealium population growth but did not
      affect R. padi population growth. Under conditions of plant water stress,
      however, the inhibitory effect of R. padi on M. festucae cerealium was not
      observed. We conclude that beneficial effects of cocolonization on R. padi are
      due to a localized plant response to M. festucae cerealium feeding, and that
      cocolonization of plants is likely to suppress M. festucae cerealium populations
      under ample water conditions, but not when plants are water stressed. This
      suggests that plant responses to water stress alter the outcome of competition
      between herbivore species, with implications for the structure of pest
      communities on wheat during periods of drought.

PMID- 28430900
TI  - Ex vivo lung perfusion; this idea deserves testing.

PMID- 28430899
TI  - Mycobacterium chimaera Infections Associated With Contaminated Heater-Cooler
      Devices for Cardiac Surgery: Outbreak Management.
AB  - The global outbreak of Mycobacterium chimaera infections associated with heater
      cooler devices (HCDs) presents several important, unique challenges for the
      infection prevention community. The primary focus of this article is to assist
      hospitals in establishing a rapid response for identification, notification, and
      evaluation of exposed patients, and management of HCDs with regard to placement
      and containment, environmental culturing, and disinfection.

PMID- 28430901
TI  - Synergistic effect between ischaemic heart disease and common mental disorders
      and the risk of premature exit from the labour market: a nationwide register
      based study from Sweden.
AB  - Aims: Common mental disorders i.e. depressive and anxiety disorders (CMD) are
      frequent comorbid conditions in individuals with ischaemic heart disease (IHD).
      Still, their effect on preterm exit from the labour market [i.e. disability
      pension (DP)] in individuals with IHD has to date not been scrutinized. The aim
      of this study was to investigate the separate and joint effect of IHD and CMD on
      the risk of DP for women and men of working age. Material and methods: This
      population-based cohort study included all non-pensioned 4 823 069 individuals,
      registered as living in Sweden 31 December 2004 and then 16-64 years of age.
      Individuals with IHD or CMD were identified through using data on sickness
      absence, prescribed medication or in- or specialized outpatient care in 2005.
      Crude and adjusted hazard ratios (HR) and 95% confidence intervals (CI) for being
      granted DP in 2006-10 were estimated by means of Cox proportional hazard
      regression. Results: In the fully adjusted models, HRs for DP were 2.84 (95% CI;
      2.57-3.13) and 2.83 (2.66-3.01) in women and men with IHD, respectively. Hazard
      ratios for DP in women and men with CMD were 5.13 (5.03-5.24) and 6.08 (5.93
      6.24). In women and men with both conditions, crude HRs for DP were 18.38 (15.01
      22.50) and 25.58 (22.27-29.37). There was a significant synergistic effect
      between IHD and CMD in both sexes in the crude models, which disappeared in women
      after adjusting for socio-demographic variables, and in men after additionally
      adjusting for comorbid somatic disorders. Conclusion: A comorbid CMD worsens the
      prognosis of IHD in terms of early exit from the labour market. Processes leading
      to DP in individuals with IHD are multifactorial and may involve the presence of
      CMD as well as comorbidity with other somatic diseases.

PMID- 28430902
TI  - Risk for hypertension crosses generations in the community: a multi-generational
      cohort study.
AB  - Aims: Parental hypertension is known to predict high blood pressure (BP) in
      children. However, the extent to which risk for hypertension is conferred across
      multiple generations, notwithstanding the impact of environmental factors, is
      unclear. Our objective was therefore to evaluate the degree to which risk for
      hypertension extends across multiple generations of individuals in the community.
      Methods and results: We studied three generations of Framingham Heart Study
      participants with standardized blood pressure measurements performed at serial
      examinations spanning 5 decades (1948 through 2005): First Generation (n = 1809),
      Second Generation (n = 2631), and Third Generation (n = 3608, mean age 39 years,
      53% women). To capture a more precise estimate of conferrable risk, we defined
      early-onset hypertension (age <55 years) as the primary exposure. In multinomial
      logistic regression models adjusting for standard risk factors as well as
      physical activity and daily intake of dietary sodium, risk for hypertension in
      the Third Generation was conferred simultaneously by presence of early-onset
      hypertension in parents [OR 2.10 (95% CI, 1.66-2.67), P < 0.001] as well as in
      grandparents [OR 1.33 (95% CI, 1.12-1.58), P < 0.01]. Conclusion: Early-onset
      hypertension in grandparents raises the risk for hypertension in grandchildren,
      even after adjusting for early-onset hypertension in parents and lifestyle
      factors. These results suggest that a substantial familial predisposition for
      hypertension exists, and this predisposition is not identical when assessed from
      one generation to the next. Additional studies are needed to elucidate the
      mechanisms underlying transgenerational risk for hypertension and its clinical
      implications.

PMID- 28430903
TI  - Costorage of Enteroendocrine Hormones Evaluated at the Cell and Subcellular
      Levels in Male Mice.
AB  - Recent studies reveal complex patterns of hormone coexpression within
      enteroendocrine cells (EECs), contrary to the traditional view that gut hormones
      are expressed individually in EECs. Moreover, different hormones have been found
      in separate subcellular vesicles. However, detailed analysis of relative
      expression of multiple hormones has not been made. Subcellular studies have been
      confined to peptide hormones, and have not included the indolamine 5
      hydroxytryptamine (5-HT) or the neuroendocrine protein chromogranin A (CgA). In
      the present work, coexpression of 5-HT, CgA, secretin, cholecystokinin (CCK),
      ghrelin, and glucagonlike peptide (GLP)-1 in mouse duodenum was quantified at a
      cellular and subcellular level by semiautomated cell counting and quantitative
      vesicle measurements. We investigated whether relative numbers of cells with
      colocalized hormones analyzed at a cell level matched the numbers revealed by
      examination of individual storage vesicles within cells. CgA and 5-HT were
      frequently expressed in EECs that contained combinations of GLP-1, ghrelin,
      secretin, and CCK. Separate subcellular stores of 5-HT, CgA, secretin, CCK,
      ghrelin, and GLP-1 were identified. In some cases, high-resolution analysis
      revealed small numbers of immunoreactive vesicles in cells dominated by a
      different hormone. Thus the observed incidence of cells with colocalized hormones
      is greater when analyzed at a subcellular, compared with a cellular, level.
      Subcellular analysis also showed that relative numbers of vesicles differ
      considerably between cells. Thus separate packaging of hormones that are
      colocalized is a general feature of EECs, and EECs exhibit substantial
      heterogeneity, including the colocalization of hormones that were formerly
      thought to be in cells of different lineages.

PMID- 28430905
TI  - Cardiac resynchronization therapy in the real world: need to focus on implant
      rates, patient selection, co-morbidities, type of devices, and complications.

PMID- 28430904
TI  - Catheter-based tricuspid valve replacement: first experimental data of a newly
      designed bileaflet stent graft prosthesis.
AB  - OBJECTIVES: Moderate or severe degree tricuspid valve regurgitation (TVR) is
      associated with high rates of morbidity and mortality. Surgical correction as the
      only therapeutic option offers unsatisfactory results. Recently, several
      interventional procedures have been introduced clinically in a limited cohort. We
      present our initial experiments with an innovative interventional valved stent
      graft for treatment of TVR. METHODS: A newly designed porcine pericardium-covered
      nitinol stent graft with a lateral bicuspid valve was adapted to size in a
      cadaver study. After haemodynamic testing in an ex vivo perfusion setup, vascular
      access, valve delivery and function were investigated in an ovine animal model (
      n  = 7). RESULTS: The device was implanted successfully in all animals. Vascular
      access was established surgically via the femoral vein without any vascular
      complications. Angiography demonstrated the correct position of the device with
      proper sealing of both venae cavae in 6 animals. In 1 extremely large animal, the
      position of the device was considered too cranial but still acceptable. Correct
      valve function was verified in all animals by both angiography and
      echocardiography. There were no persistent arrhythmias other than during valve
      implant. All animals survived the implant procedure and were sacrificed
      electively. CONCLUSIONS: This study demonstrated that this new valved stent graft
      could be delivered safely with correct positioning and valve function in this
      ovine model. Further long-term studies in animals implanted with the device after
      creation of tricuspid regurgitation are necessary to prove the haemodynamic
      benefit of this procedure.

PMID- 28430907
TI  - Food Intake Affects Sperm-Egg Fusion Through the GIP/PSG17 Axis in Mice.
AB  - In addition to overeating, starvation also reduces fecundity in mammals. However,
      little is known about the molecular mechanisms linking food intake to fertility,
      especially in males. Gastric inhibitory polypeptide (GIP), which is released from
      intestinal K-cells after meal ingestion, stimulates insulin secretion from
      pancreatic beta-cells through the action of incretin and has several
      extrapancreatic effects. Here, we identified GIP receptor (Gipr) expression in
      mouse spermatids. Microarray analysis revealed that pregnancy-specific
      glycoprotein 17 (Psg17), a potential CD9-binding partner, was significantly
      decreased in GIP receptor-knockout (Gipr-/-) testes. Glycosylphosphatidylinositol
      anchored PSG17 was expressed on the surface of acrosome-reacted sperm, and Gipr-/
      sperm led to a lower fertilization rate in vitro, compared with that of Gipr+/+
      sperm, both in the absence and presence of the zona pellucida. Plasma GIP
      concentrations and Psg17 messenger RNA (mRNA) were immediately increased in the
      testis after a single meal, whereas ingestion of a chronic high-fat diet markedly
      decreased Gipr and Psg17 mRNA. These results suggest that reduced GIP signaling,
      by decreased GIP levels or the downregulation of Gipr, is associated with the
      reduction of fecundity due to starvation or overeating. Thus, proper regulation
      of GIP signaling in the testis could be a potential unique therapeutic target for
      male infertility in obese and diabetic individuals.

PMID- 28430906
TI  - Past and current cause-specific mortality in Eisenmenger syndrome.
AB  - Aims: Eisenmenger syndrome (ES) is associated with considerable morbidity and
      mortality. Therapeutic strategies have changed during the 2000s in conjunction
      with an emphasis on specialist follow-up. The aim of this study was to determine
      the cause-specific mortality in ES and evaluate any relevant changes between 1977
      and 2015. Methods and results: This is a retrospective, descriptive multicentre
      study. A total of 1546 patients (mean age 38.7 +/- 15.4 years; 36% male) from 13
      countries were included. Cause-specific mortality was examined before and after
      July 2006, 'early' and 'late', respectively. Over a median follow-up of 6.1 years
      (interquartile range 2.1-21.5 years) 558 deaths were recorded; cause-specific
      mortality was identified in 411 (74%) cases. Leading causes of death were heart
      failure (34%), infection (26%), sudden cardiac death (10%), thromboembolism (8%),
      haemorrhage (7%), and peri-procedural (7%). Heart failure deaths increased in the
      'late' relative to the 'early' era (P = 0.032), whereas death from thromboembolic
      events and death in relation to cardiac and non-cardiac procedures decreased (P =
      0.014, P = 0.014, P = 0.004, respectively). There was an increase in longevity in
      the 'late' vs. 'early' era (median survival 52.3 vs. 35.2 years, P < 0.001).
      Conclusion: The study shows that despite changes in therapy, care, and follow-up
      of ES in tertiary care centres, all-cause mortality including cardiac remains
      high. Patients from the 'late' era, however, die later and from chronic rather
      than acute cardiac causes, primarily heart failure, whereas peri-procedural and
      deaths due to haemoptysis have become less common. Lifelong vigilance in tertiary
      centres and further research for ES are clearly needed.

PMID- 28430908
TI  - Late thrombotic events after bioresorbable scaffold implantation: a systematic
      review and meta-analysis of randomized clinical trials.
AB  - Aims: To compare the long-term safety and efficacy of bioresorbable vascular
      scaffold (BVS) with everolimus-eluting stent (EES) after percutaneous coronary
      interventions. Methods and results: A systematic review and meta-analysis of
      randomized clinical trials comparing clinical outcomes of patients treated with
      BVS and EES with at least 24 months follow-up was performed. Adjusted random
      effect model by the Knapp-Hartung method was used to compute odds ratios (OR) and
      95% confidence intervals (CI). The primary safety outcome of interest was the
      risk of definite/probable device thrombosis (DT). The primary efficacy outcome of
      interest was the risk of target lesion failure (TLF). Five randomized clinical
      trials (n = 1730) were included. Patients treated with Absorb BVS had a higher
      risk of definite/probable DT compared with patients treated with EES (OR 2.93,
      95%CI 1.37-6.26, P = 0.01). Very late DT (VLDT) occurred in 13 patients [12/996
      (1.4%, 95%CI: 0.08-2.5) Absorb BVS vs. 1/701 (0.5%, 95%CI: 0.2-1.6) EES; OR 3.04;
      95%CI 1.2-7.68, P = 0.03], 92% of the VLDT in the BVS group occurred in the
      absence of dual antiplatelet therapy (DAPT). Patients treated with Absorb BVS had
      a trend towards higher risk of TLF (OR 1.48, 95%CI 0.90-2.42, P = 0.09), driven
      by a higher risk of target vessel myocardial infarction and ischaemia-driven
      target lesion revascularization. No difference was found in the risk of cardiac
      death. Conclusion: Compared with EES, the use of Absorb BVS was associated with a
      higher rate of DT and a trend towards higher risk of TLF. VLDT occurred in 1.4%
      of the patients, the majority of these events occurred in the absence of DAPT.

PMID- 28430909
TI  - Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in
      Surgical Prosthesis.
AB  - The VARC (Valve Academic Research Consortium) for transcatheter aortic valve
      replacement set the standard for selecting appropriate clinical endpoints
      reflecting safety and effectiveness of transcatheter devices, and defining single
      and composite clinical endpoints for clinical trials. No such standardization
      exists for circumferentially sutured surgical valve paravalvular leak (PVL)
      closure. This document seeks to provide core principles, appropriate clinical
      endpoints, and endpoint definitions to be used in clinical trials of PVL closure
      devices. The PVL Academic Research Consortium met to review evidence and make
      recommendations for assessment of disease severity, data collection, and updated
      endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in
      concordance with VARC recommendations. Unresolved issues in the field are
      outlined. The current PVL Academic Research Consortium provides recommendations
      for assessment of disease severity, data collection, and endpoint definitions.
      Future research in the field is warranted.

PMID- 28430912
TI  - A Birth Story: Cortisol-Stimulated Autophagy in Parturition.

PMID- 28430910
TI  - Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for
      patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a
      prospective, open-label, randomized trial.
AB  - Aims: To elucidate the effects of intensive LDL-C lowering treatment with a
      standard dose of statin and ezetimibe in patients with dyslipidaemia and high
      risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L),
      compared with standard LDL-C lowering lipid monotherapy targeting less than 100
      mg/dL (2.6 mmol/L). Methods and results: The HIJ-PROPER study is a prospective,
      randomized, open-label trial to assess whether intensive LDL-C lowering with
      standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than
      standard LDL-C lowering with pitavastatin monotherapy in patients with acute
      coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive
      lowering (target LDL-C < 70 mg/dL [1.8 mmol/L]; pitavastatin plus ezetimibe) or
      standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3-2.6 mmol/L];
      pitavastatin monotherapy). The primary endpoint was a composite of all-cause
      death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and
      ischaemia-driven revascularization. Between January 2010 and April 2013, 1734
      patients were enroled at 19 hospitals in Japan. Patients were followed for at
      least 36 months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1
      mg/dL (1.68 mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19 mmol/L)
      for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not
      reduce primary endpoint occurrence in comparison with standard statin monotherapy
      (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76-1.04, P = 0.152). In,
      ACS patients with higher cholesterol absorption, represented by elevated pre
      treatment sitosterol, was associated with significantly lower incidence of the
      primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56-0.91).
      Conclusion: Although intensive lowering with standard pitavastatin plus ezetimibe
      showed no more cardiovascular benefit than standard pitavastatin monotherapy in
      ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than
      statin monotherapy in patients with higher cholesterol absorption; further
      confirmation is needed. Trial No: UMIN000002742, registered as an International
      Standard Randomized Controlled Trial.

PMID- 28430911
TI  - A devices' game of thrones: cardiac resynchronization therapy vs. pacemaker.
AB  - Aims: Oversensing can interfere with biventricular pacing. Cardiac
      Resynchronization Therapy (CRT) output inhibition due to automatic brady mode
      change from a sensing to a pacing mode of a previously implanted pacemaker as it
      reached battery capacity depleted indicator has not been previously published in
      the medical literature. Methods and results: We report the first case of CRT
      output inhibition in a pacemaker dependent patient due to electrical stimuli from
      a previously right-sided implanted pacemaker, after unaware reversion of OVO mode
      (O = no chambers paced; V = ventricular sensing; O = no response to sensing) to
      backup VVI (V = ventricular pacing; V = ventricular sensing; I = inhibitory
      response to sensing) when it reached the elective replacement interval.
      Conclusion: This paper emphasizes the importance of knowing the distinct
      pacemaker brady mode behaviours after battery capacity depleted indicator has
      been reached, according to the pacemakers' manufacturer, including the
      possibility of automatic brady mode change from sensing to pacing mode. It also
      highlights the potential for severe bradycardia or asystole of this automatic
      brady mode change from a previously implanted pacemaker in pacemaker dependent
      patients submitted to CRT upgrade.

PMID- 28430914
TI  - Finding the Right Balance: Androgens at the Tipping Point of Fertility and
      Metabolism in Women.

PMID- 28430913
TI  - Prediction of adverse events after catheter-based procedures in adolescents and
      adults with congenital heart disease in the IMPACT registry.
AB  - Aims: We sought to identify factors associated with major adverse events (MAE)
      after cardiac catheterization in adolescents and adults with congenital heart
      disease (CHD), and create the first model to individualize risk discussions in
      this growing population. Methods and results: Improving Pediatric and Adult
      Congenital Treatment (IMPACT), a National Cardiovascular Data Registry, contains
      congenital catheterization data from over 87 hospitals in the United States.
      Demographics, pre-procedure, and procedural variables were collected for patients
      over age 10. Multivariable logistic regression was used to identify significant
      predictors of MAE, a composite of death, urgent surgery or procedure due to a
      catheterization complication, transfusion, embolic stroke, tamponade,
      extracorporeal membrane oxygenation or ventricular assist device placement, and
      device embolization, malposition or thrombosis requiring surgical intervention. A
      risk score was built based on the effect sizes of each predictor and validated in
      a split sample. A MAE occurred in 686 (2.5%) of the 27 293 index procedures
      meeting inclusion criteria. The independent multivariate predictors of MAE were
      older age, pre-procedural anticoagulation use, renal disease, lower haemoglobin,
      lower oxygen saturation, non-elective procedure, higher index procedure risk and
      having had no prior cardiac procedures. Being underweight or overweight had
      borderline significance and was added to the model. The C-statistic for the model
      was robust at 0.787 in the derivation and 0.773 in the validation cohort.
      Conclusion: The factors predicting adverse events after cardiac catheterization
      in adolescents and adults with CHD are different than in the general population.
      Validation of this model in other national or multi-institutional datasets is the
      next step.

PMID- 28430915
TI  - Genetic Knockout and Rescue Studies in Mice Unravel Abnormal Phosphorus Threshold
      in Hypophosphatemic Rickets.

PMID- 28430916
TI  - Osteoclasts Control Lipid Secretion to Regulate Breast Cancer Bone Metastasis.

PMID- 28430917
TI  - PKA Differentially Regulates Adipose Depots to Control Energy Expenditure.

PMID- 28430918
TI  - The "Plastic" Mother.

PMID- 28430919
TI  - Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic
      perspectives.
AB  - Recent research has demonstrated that the non-coding genome plays a key role in
      genetic programming and gene regulation during development as well as in health
      and cardiovascular disease. About 99% of the human genome do not encode proteins,
      but are transcriptionally active representing a broad spectrum of non-coding RNAs
      (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have
      been identified as critical novel regulators of cardiovascular risk factors and
      cell functions and are thus important candidates to improve diagnostics and
      prognosis assessment. Beyond this, ncRNAs are rapidly emgerging as fundamentally
      novel therapeutics. On a first level, ncRNAs provide novel therapeutic targets
      some of which are entering assessment in clinical trials. On a second level, new
      therapeutic tools were developed from endogenous ncRNAs serving as blueprints.
      Particularly advanced is the development of RNA interference (RNAi) drugs which
      use recently discovered pathways of endogenous short interfering RNAs and are
      becoming versatile tools for efficient silencing of protein expression.
      Pioneering clinical studies include RNAi drugs targeting liver synthesis of PCSK9
      resulting in highly significant lowering of LDL cholesterol or targeting liver
      transthyretin (TTR) synthesis for treatment of cardiac TTR amyloidosis. Further
      novel drugs mimicking actions of endogenous ncRNAs may arise from exploitation of
      molecular interactions not accessible to conventional pharmacology. We provide an
      update on recent developments and perspectives for diagnostic and therapeutic use
      of ncRNAs in cardiovascular diseases, including atherosclerosis/coronary disease,
      post-myocardial infarction remodelling, and heart failure.

PMID- 28430920
TI  - Rates and predictors of hospital readmission after transcatheter aortic valve
      implantation.
AB  - Aims: To analyse reasons, timing and predictors of hospital readmissions after
      transcatheter aortic valve implantation (TAVI). Methods and results: Patients
      included in the Bern TAVI Registry between August 2007 and June 2014 were
      analysed. Fine and Gray competing risk regression was used to identify factors
      predictive of hospital readmission within 1 year after TAVI with bootstrap
      analysis for internal validation. Of 868 patients alive at discharge, 221 (25.4%)
      were readmitted within 1 year. Compared with patients not requiring readmission,
      those with at least one readmission more frequently were male and more often had
      atrial fibrillation and higher creatinine values (P < 0.05 for all cases). For
      overall 308 readmissions, cardiovascular causes accounted for 46.1% with heart
      failure as the most frequent indication; non-cardiovascular readmissions occurred
      for surgery (11.7%), gastrointestinal disorders (9.7%), malignancy (4.9%),
      respiratory diseases (4.6%) and chronic kidney failure (2.6%). Male gender
      (subhazard ratio, SHR, 1.33, 95% confidence intervals, CI, 1.02-1.73, P = 0.035)
      and stage 3 kidney injury (SHR 2.04, 95% CI 1.12-3.71, P = 0.021) were found
      independent risk factors for any hospital readmission, whereas previous
      myocardial infarction (SHR 1.88, 95% CI 1.22-2.90, P = 0.004) and in-hospital
      life-threatening bleeding (SHR 2.18, 95%CI 1.24-3.85, P = 0.007) were associated
      with cardiovascular readmissions. The event rate for mortality was significantly
      increased after readmissions for any cause (RR 4.29, 95% CI 2.86-6.42, P <
      0.001). Conclusion: Hospital readmission was observed in one out of four patients
      during the first year after TAVI and was associated with a significant increase
      in mortality.

PMID- 28430922
TI  - Yet Another Scenario in the Regulation of the Steroidogenic Acute Regulatory
      (STAR) Protein Gene.

PMID- 28430921
TI  - Association Between Cardiovascular Health and Endothelial Function With Future
      Erectile Dysfunction: The Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: The association of Cardiovascular Health (CVH; defined by the
      American Heart Association by assigning points for health-related behavioral and
      clinical factors) with endothelial and erectile dysfunction has not been
      reported, although endothelial and erectile dysfunction have been associated with
      components of CVH. METHODS: Data were collected in 1,136 men in the Multi-Ethnic
      Study of Atherosclerosis at baseline and erectile dysfunction status (measured by
      survey or medication use) at exam 5. CVH was determined with 7 health metrics.
      Endothelial function was measured with brachial artery flow-mediated dilation
      (FMD). Poisson regression was used to determine associations between CVH and
      erectile dysfunction across categories of CVH (low, moderate, and high). RESULTS:
      Age and proportion of Black or Latino participants decreased while proportion of
      Chinese-American participants increased with higher CVH category. FMD was higher
      in men without erectile dysfunction and higher in men with high vs. low CVH.
      Erectile dysfunction prevalence was lower with better CVH; 58% in men with low
      CVH, 41% with moderate CVH, and 33% with high CVH (P < 0.001). CVH was associated
      with erectile dysfunction; prevalence ratio = 0.75 (95% confidence interval (CI)
      = 0.66, 0.84) with moderate CVH and 0.68 (95% CI = 0.49, 0.94) with high CVH (vs.
      men with low CVH) and 0.93 (95% CI = 0.91, 0.96) for every 1-point higher CVH
      score in a fully adjusted model, including FMD, age, education, depression score,
      use of antidepressant or beta-blocker medications, chronic disease, heavy
      drinking, and race. CONCLUSION: CVH is associated with future erectile
      dysfunction, even after adjustment for baseline FMD. Maintaining high CVH may
      improve quality of life for men.

PMID- 28430923
TI  - Spatiotemporal Regulation of Insulin-Like Growth Factor-1 and Its Receptor in the
      Brain: Is There a Role for Growth Hormone?

PMID- 28430924
TI  - Who Are You and Where Am I? New Insights Into How Animals Determine Their Social
      Context.

PMID- 28430925
TI  - Islet Endothelial Cell: Friend and Foe.

PMID- 28430926
TI  - The Association Between Alcohol-Flavoured Non-Alcoholic Beverages and Alcohol Use
      in Japanese Adolescents.
AB  - Aims: There are no legal regulations in Japan governing minors' consumption of
      alcohol-flavoured non-alcoholic beverages (AFNAB); therefore, we examined if
      their consumption could lead to increased alcohol use among adolescents in Japan.
      Methods: This cross-sectional study used a nonclinical, nationally representative
      sample of 38,494 junior (19,662 boys) and 61,556 senior (31,925 boys) high school
      students recruited in 2012. We measured AFNAB consumption rates and the order
      that adolescents first consumed AFNAB and alcohol. Results: The AFNAB consumption
      was strongly associated with alcohol use in high school students. Among all age
      groups, alcohol was more commonly consumed before AFNAB for both males and
      females. Conclusions: Consumption of AFNAB is more prevalent among minors than
      alcohol consumption and it has a strong association with alcohol consumption.
      However, concerns that AFNAB use would lead to increased alcohol use were not
      supported because AFNAB consumption usually started after adolescents began
      consuming alcohol. Short Summary: Consumption of AFNAB is more prevalent among
      high school students than alcohol consumption and it has a strong association
      with alcohol consumption. However, concerns that AFNAB use would lead to
      increased alcohol use were not supported because AFNAB consumption usually
      started after adolescents began consuming alcohol.

PMID- 28430927
TI  - The Association Between Health Changes and Cessation of Alcohol Consumption.
AB  - Aims: To assess whether health changes affect cessation of alcohol consumption
      and to compare the health status of former drinkers and abstainers. Methods:
      Cohort data from 9001 Korean participants aged 40-69 years old were analyzed.
      Alcohol consumption was assessed every 2 years for 10 years. Participant age,
      sex, marital status, education level, employment status, smoking, chronic
      disease, perceived health and changes in these variables were analyzed to
      identify factors associated with quitting alcohol drinking. The number of
      diseases and perceived health of former drinkers and people who at baseline were
      lifetime abstainers were compared. Results: Among 4037 drinkers at baseline, 673
      (16.7%) were classed as quitters and 3364 (83.3%) were classed as non-quitters.
      Sex, age and worsened perception of health were significantly associated with
      cessation of drinking. Women and individuals >60 years were more likely to cease
      drinking. There was a significant association between disease onset or treatment
      and alcohol cessation for cancer cases, but not for cardiovascular disease or
      chronic disease cases. There was no significant difference in number of diseases
      or perceived health between former drinkers and people who at baseline were
      lifetime abstainers. Conclusions: The effect of disease onset or treatment on
      alcohol consumption cessation depended on disease type. Former drinkers did not
      show significantly worse health than people who at baseline were lifetime
      abstainers. Further studies of alcohol consumption and its effects on health are
      needed to consider disease occurrence and changes in alcohol consumption. Short
      summary: Disease onset or treatment significantly affected alcohol consumption
      cessation for cancer cases, but not for cardiovascular disease or other chronic
      disease cases. There was no significant difference in health status between
      former drinkers and lifetime abstainers.

PMID- 28430928
TI  - Typology and Dynamics of Heavier Drinking Styles in Great Britain: 1978-2010.
AB  - Aims: To identify a typology of heavier drinking styles in Great Britain and to
      identify socio-demographic trends in the typology over the period 1978-2010.
      Methods: We applied multiple correspondence analysis and agglomerative
      hierarchical clustering to beverage-specific quantity-frequency measures of
      alcohol consumption in the repeated cross-sectional General Lifestyle Survey of
      Great Britain, 1978-2010. The cluster analysis focuses on the 60,043 adult
      respondents over this period reporting average drinking levels above the UK
      Government guidelines. We projected sex, age, income, education, socio-economic
      status and tobacco consumption variables onto the clusters to inspect socio
      demographic trends in heavier drinking. Results: We identified four stable
      clusters of heavier drinking: (a) high volume beer; (b) beer and spirit
      combination; (c) all beverage and (d) wine and spirit only. The socio-demographic
      characteristics of the clusters were distinct from both each other and the
      general population. However, all clusters had higher median incomes and higher
      smoking rates than the population. Increases in the prevalence of heavier
      drinking were driven by a 5-fold increase in the contribution of the female
      dominated, wine and spirit only cluster. Conclusions: Recent changes in per
      capita alcohol consumption in Great Britain occurred within the context of a
      stable typology of heavier drinking styles and shifting socio-demographics.
      Identifying these trends is essential to better understand how drinking cultures
      develop over time and where potentially problematic drinking styles may emerge.
      Our findings suggest that careful attention to patterns and cultures of
      consumption is more important than relying on headline consumption data, for both
      understanding drinking behaviours and targeting interventions. Short Summary:
      This analysis of alcohol consumption survey data identifies four styles of
      heavier drinking in Great Britain, which remain unchanged over the period 1978
      2010. The socio-demographic characteristics of the drinking styles are distinct
      from both each other and the general population, with increased participation of
      female and older drinkers over time.

PMID- 28430929
TI  - Promoter Polymorphism rs886205 Genotype Interacts With DNA Methylation of the
      ALDH2 Regulatory Region in Alcohol Dependence.
AB  - Aims: Aldehyde dehydrogenase 2 (ALDH2) protects cells from ethanol toxicity by
      metabolizing acetaldehyde. We studied the single nucleotide polymorphism (SNP)
      rs886205s located between a negative and a positive regulating promoter element
      in the ALDH2 gene. The negative regulatory region was already associated with
      differential DNA methylation in the two allele variations of rs886205 SNP.
      Another CpG island, in the positive regulatory region of the ALDH2 promoter,
      extends through the SNP rs886205 and a nuclear receptor response element.
      Methods: We assessed rs886305 genotype and DNA methylation using bisulfite
      sequencing in a cohort of 83 male alcohol-dependent patients undergoing
      detoxification treatment (Days 1, 7 and 14) and in 33 male age-matched controls.
      Luciferase reporter assays were performed to address the functional significance
      of genotype and methylation. Results: We observed a higher methylation in alcohol
      dependent patients compared to controls. Patients with AA (n = 52) or GG/GA (n =
      31) genotype differed significantly in baseline methylation levels as well as in
      methylation kinetics during withdrawal. AA carriers display an increase in
      methylation from low baseline levels while GG/GA showed the inverse pattern. The
      reporter gene assays corroborate these data by showing a significant effect of
      genotype on ALDH2 expression as well as an interaction between genotype and
      methylation. Conclusion: Our results describe a new regulatory role of rs886205
      in the methylation of ALDH2 promoter region and provide additional insight into
      the complex regulation of ALDH2 under the condition of alcohol dependence. Short
      summary: Genetic variations have been described to influence DNA promoter
      methylation of various genes. We investigated the association between the
      polymorphism rs886205, located on ALDH2 promoter and methylation kinetics of the
      neighboring CpG island in alcohol-dependent patients. Luciferase reporter assays
      showed functional significance of genotype, methylation and a genotype
      epigenotype interaction in vitro.

PMID- 28430930
TI  - Alcohol Consumption and Binge Drinking in Young Men as Predictors of Body
      Composition Changes During Military Service.
AB  - Aims: To evaluate the influences of alcohol consumption frequency and binge
      drinking on changes in the body composition, lifestyle habits and physical
      fitness of healthy young men during military service. Methods: A population-based
      study of men performing their military service in the Sodankyla Jaeger Brigade,
      Finland in 2005. Body composition, fitness and lifestyle habits were evaluated at
      baseline and 6-12 months follow-up. Alcohol consumption frequency and binge
      drinking were categorized as: 'not at all', 'at least once a month' and 'at least
      once a week'. Results: Data were available for 983 participants. Mean (SD) age
      was 19.2 (1.0) years. At baseline, participants who reported binge drinking at
      least once a week (29.8%) had the most unfavourable body composition, lifestyle
      habits and physical fitness compared with the group with no binge drinking.
      Significant (P < 0.05) mean reductions in % body fat (-2.3%) and weight (-1.8
      kg), as well as improvements in lifestyle habits and physical fitness were
      observed in the weekly binge drinking group during the military service. The
      reductions in relative weight (%) and % body fat were associated with binge
      drinking at least once a week (regression coefficient for relative weight -1.39,
      95% CI [-2.32; -0.45], P = 0.004, and for % body fat -0.68, 95% CI [-1.35; 
      0.01], P = 0.049). Conclusion: Frequent binge drinking is associated with poorer
      body composition, lifestyle habits and fitness among young men. Frequent binge
      drinkers may obtain the greatest benefit of military-service-based exercise
      intervention, as reflected in the improvements in body composition, lifestyle
      habits and physical fitness. Short summary: Frequent binge drinking is associated
      with poorer body composition, lifestyle habits and fitness among young men. The
      greatest benefit of military service comprehending exercise intervention was
      observed among those with binge drinking once a week at the baseline, with
      favourable changes in lifestyle factors, body composition and fitness.

PMID- 28430931
TI  - Joint Effects of the Epigenetic Alteration of Neurotrophins and Cytokine
      Signaling: A Possible Exploratory Model of Affective Symptoms in Alcohol
      Dependent Patients?
AB  - Aims: Neurotrophins have been linked to the symptomatology of alcohol dependence.
      We aimed to investigate a possible association between the methylation of the
      promoters of both neurotrophins, the serum levels of the cytokines and core
      symptoms of alcohol dependence as withdrawal severity and anxiety. Methods: In
      this study we investigated a possible association between alterations in the
      methylation of the BDNF IV/NGF I gene promoter and the cytokines tumor necrosis
      factor alpha (TNF-alpha) and interleukin-6 (IL-6) in 55 male alcohol-dependent
      patients. Results: Mean methylation of the promoter of the BDNF gene was
      significantly associated with the TNF-alpha serum levels and the CIWA-score
      during withdrawal (P < 0.001). Moreover, mean methylation of the NGF I promoter
      was significantly associated with the IL-6 serum levels and STAI-I score during
      withdrawal (P < 0.001). Conclusion: Our results suggest an association between
      the epigenetic regulation of both neurotrophins, BDNF and NGF, cytokine release
      and the symptomatology of alcohol dependence. They imply that changes in the
      methylation of neurotrophins may contribute to the symptomatology of alcohol
      dependence by affecting relevant downstream signaling cascades.

PMID- 28430932
TI  - Ethnic Variations in Liver- and Alcohol-Related Disease Hospitalisations and
      Mortality: The Scottish Health and Ethnicity Linkage Study.

PMID- 28430933
TI  - Acute Pancreatitis: Impact of Alcohol Consumption and Seasonal Factors.
AB  - Aims: We aimed to evaluate the potential relation between the incidence of
      (alcoholic and non-alcoholic) acute pancreatitis (AP) and alcohol consumption in
      the general population, and whether the occurrence of AP shows any seasonal
      variation, particularly in relation to periods with expected increased alcohol
      consumption. Methods: All patients with first-time AP between 2003 and 2012 in a
      well-defined area in Sweden were retrospectively identified. Data on AP aetiology
      (alcoholic and non-alcoholic) and severity were registered. Data on annual
      alcohol sales as well as on self-reported alcohol consumption were obtained.
      Results: In total, 1457 AP patients were included (83% non-alcoholic AP, 17%
      alcoholic AP). The overall AP incidence showed increasing time trends for women
      and men (P < 0.05), but there were no significant changes in the incidence of
      alcoholic AP, in either sex (P > 0.05). Alcohol sales during the study period
      decreased (P = 0.002), mainly due to decreased sales of spirits (P = 0.001) and
      beer (P = 0.002), while self-reported alcohol consumption remained stable for
      women (P > 0.05) and decreased for men (P = 0.022). Neither alcohol sales nor
      consumption was related to the time trends of AP (P > 0.05 for all). No
      significant differences were found in the occurrence of AP among different
      seasons of the year or between holidays associated with higher alcohol
      consumption compared to periods before and after these holidays (P > 0.05 for
      all). Conclusions: Changes in alcohol consumption in the general population do
      not appear to be related to changes in the incidence of AP and there are no
      significant seasonal differences in the occurrence of AP in Sweden. Short
      summary: The incidence of acute pancreatitis (AP) is increasing, and alcohol is
      still recognized as one of the most common causes. In this study, however, we
      could not ascertain any clear relations between the sales and consumption of
      alcohol in the general population and the incidence of alcoholic or non-alcoholic
      AP.

PMID- 28430934
TI  - Price Elasticity of Alcohol Demand in India.
AB  - Aims: Using a household survey conducted in 2014, this study estimates price
      elasticity of demand (PED) for beer, country liquor and spirits in India.
      Methods: Ordinary least-square models were used to estimate the responsiveness in
      alcohol demand due to price change. A large number of control variables were
      included to adjust for potential confounding in the model. Inter-district
      variation in alcohol consumption is adjusted for by including district fixed
      effects. Results: Alcohol prices are negatively associated with demand for
      alcoholic beverages. The PED ranged from -0.14 for spirits to -0.46 for country
      liquor. Low level of education was positively associated with spirits
      consumption. The magnitude of elasticity varied by rural-urban, education and
      gender. Conclusion: Results indicate that a policy mix of price controls and
      awareness campaigns would be most effective in tackling the adverse effects of
      harmful drinking in India. Summary: The demand for beer, country liquor and
      spirits is negatively associated with its own price. The elasticity estimates
      ranged from -0.14 for spirits to -0.44 for country liquor. The elasticity
      estimates varied by rural-urban, gender and by education levels of the drinkers.

PMID- 28430935
TI  - Sensation Seeking and Adolescent Alcohol Use: Exploring the Mediating Role of
      Unstructured Socializing With Peers.
AB  - Background: Researchers have theorized that adolescents high in sensation seeking
      are particularly sensitive to positive reinforcement and the rewarding outcomes
      of alcohol use, and thus that the personality vulnerability is a direct causal
      risk factor for alcohol use. In contrast, the routine activity perspective
      theorizes that part of the effect of sensation seeking on alcohol use goes
      through the propensity that sensation seekers have towards unstructured
      socializing with peers. The study tests a model with indirect and direct paths
      from sensation seeking and participation in unstructured peer socialization to
      adolescent alcohol use. Methods: Cross-sectional data were collected from 360
      students in a state-secular Jewish high school (10th to 12th grade) in the center
      region of Israel. The sample was equally divided between boys (51.9%) and girls
      (48.1%), respondents' age ranged from 15 to 17 years (mean = 16.02 +/- 0.85).
      Structural equation modeling was used to test the direct and indirect paths.
      Results: While sensation seeking had a significant direct path to adolescent
      alcohol use, part of the association was mediated by unstructured socializing
      with peers. The mediated paths were similar for boys and girls alike.
      Conclusions: Sensation seeking is primarily biologically determined and
      prevention efforts are unlikely to modify this personality vulnerability. The
      results of this study suggest that a promising prevention avenue is to modify
      extracurricular participation patterns of vulnerable adolescents.

PMID- 28430937
TI  - High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the
      Male Rat.
AB  - Oxytocin is a potent anorexigen and is believed to have a role in satiety
      signaling. We developed rat models to study the activity of oxytocin neurons in
      response to voluntary consumption or oral gavage of foods using c-Fos
      immunohistochemistry and in vivo electrophysiology. Using c-Fos expression as an
      indirect marker of neural activation, we showed that the percentage of
      magnocellular oxytocin neurons expressing c-Fos increased with voluntary
      consumption of sweetened condensed milk (SCM). To model the effect of food in the
      stomach, we gavaged anesthetized rats with SCM. The percentage of supraoptic
      nucleus and paraventricular nucleus magnocellular oxytocin-immunoreactive neurons
      expressing c-Fos increased with SCM gavage but not with gastric distention. To
      further examine the activity of the supraoptic nucleus, we made in vivo
      electrophysiological recordings from SON neurons, where anesthetized rats were
      gavaged with SCM or single cream. Pharmacologically identified oxytocin neurons
      responded to SCM gavage with a linear, proportional, and sustained increase in
      firing rate, but cream gavage resulted in a transient reduction in firing rate.
      Blood glucose increased after SCM gavage but not cream gavage. Plasma osmolarity
      and plasma sodium were unchanged throughout. We show that in response to high
      sugar, but not high-fat, food in the stomach, there is an increase in the
      activity of oxytocin neurons. This does not appear to be a consequence of stomach
      distention or changes in osmotic pressure. Our data suggest that the presence of
      specific foods with different macronutrient profiles in the stomach
      differentially regulates the activity of oxytocin neurons.

PMID- 28430936
TI  - Preliminary Evaluation of the NIAAA/AAP Brief Alcohol Use Screener.
AB  - Aims: To assess the concurrent validity of the two-item NIAAA/American Academy of
      Pediatrics Brief Alcohol Use Screener, a developmentally sensitive assessment
      instrument, in a school-based sample of adolescents. Method: The sample consisted
      of 756 adolescents (53% girls; Mage = 13.7 years; SD = 1.6 years) in the 6th (n =
      192), 8th (n = 283), and the 10th (n = 281) grades from Miami-Dade County, FL and
      Prince George's County, MD. Adolescents completed the NIAAA/AAP Brief Alcohol Use
      Screener, which consists of two items asking about adolescents' alcohol use and
      about peers' alcohol use during the last year. Peer-Risk is categorized into 'No
      Peer-Risk' versus 'Heightened Concern'; Self-Risk is categorized into 'No-Risk,'
      'Low-Risk,' 'Moderate-Risk' or 'High-Risk,' based on alcohol use patterns and
      age. Adolescents also completed measures of recent alcohol use and four
      previously validated screener instruments. Results: Relative to the self-use 'No
      Risk' category, adolescents classified into the 'Low-,' 'Moderate-' and 'High
      Risk' categories reported progressively greater alcohol use and misuse during the
      last 90 days. Similar patterns were observed between the Peer-Risk categories.
      Combined, the two NIAAA/AAP screener items were positively related to recent
      alcohol use and outperformed the other screeners examined. Conclusions: Results
      from the present study support the concurrent validity of the single and combined
      items of the NIAAA/AAP Brief Alcohol Use Screener, as well as the measure's
      favorable concurrent validity compared to four previously validated screener
      instruments. Short Summary: The current results support the concurrent validity
      of the single and combined items of the NIAAA/AAP Brief Alcohol Use Screener, as
      well as the measure's favorable concurrent validity compared to four previously
      validated screener instruments, in a school-based sample of adolescents.

PMID- 28430938
TI  - Characterization of YjjJ toxin of Escherichia coli.
AB  - Reminiscent of eukaryotic apoptotic programmed cell death, bacteria also contain
      a large number of suicide genes, which are in general co-expressed with their
      cognate antitoxin genes. These systems called the toxin-antitoxin (TA) systems
      are associated with cellular dormancy, and play major roles in biofilm formation
      and persistent multidrug resistance of many human pathogens. In recent years, the
      study on TA system toxins has become a hot topic due to the health implications
      of these toxins by virtue of their role in bacterial pathogenicity. Here we
      report functional characterization of a hitherto uncharacterized Escherichia coli
      TA toxin, YjjJ. YjjJ exhibits several uncommon properties: (i) unlike the genes
      encoding most type II TA system toxins, the gene encoding YjjJ is present as a
      single gene and not in an operon, (ii) despite being a homolog of the well
      characterized toxin HipA, YjjJ seems to have different cellular target(s), and
      (iii) HipB, the cognate antitoxin of HipA, also acts as an antitoxin for YjjJ.
      This forms a basis for an interesting next step in the study of TA systems with
      respect to cross-regulation between various TA systems and the evolutionary as
      well as clinical significance of these observations.

PMID- 28430939
TI  - Visualizing induced silent steam pop with intracardiac echocardiography.

PMID- 28430940
TI  - Unraveling microbial ecology of industrial-scale Kombucha fermentations by
      metabarcoding and culture-based methods.
AB  - Kombucha, historically an Asian tea-based fermented drink, has recently become
      trendy in Western countries. Producers claim it bears health-enhancing properties
      that may come from the tea or metabolites produced by its microbiome. Despite its
      long history of production, microbial richness and dynamics have not been fully
      unraveled, especially at an industrial scale. Moreover, the impact of tea type
      (green or black) on microbial ecology was not studied. Here, we compared
      microbial communities from industrial-scale black and green tea fermentations,
      still traditionally carried out by a microbial biofilm, using culture-dependent
      and metabarcoding approaches. Dominant bacterial species belonged to
      Acetobacteraceae and to a lesser extent Lactobacteriaceae, while the main
      identified yeasts corresponded to Dekkera, Hanseniaspora and Zygosaccharomyces
      during all fermentations. Species richness decreased over the 8-day fermentation.
      Among acetic acid bacteria, Gluconacetobacter europaeus, Gluconobacter oxydans,
      G. saccharivorans and Acetobacter peroxydans emerged as dominant species. The
      main lactic acid bacteria, Oenococcus oeni, was strongly associated with green
      tea fermentations. Tea type did not influence yeast community, with Dekkera
      bruxellensis, D. anomala, Zygosaccharomyces bailii and Hanseniaspora valbyensis
      as most dominant. This study unraveled a distinctive core microbial community
      which is essential for fermentation control and could lead to Kombucha quality
      standardization.

PMID- 28430941
TI  - Vagal third-degree atrioventricular block in a highly trained endurance athlete.

PMID- 28430942
TI  - Short-term responses and resistance of soil microbial community structure to
      elevated CO2 and N addition in grassland mesocosms.
AB  - Nitrogen (N) addition is known to affect soil microbial communities, but the
      interactive effects of N addition with other drivers of global change remain
      unclear. The impacts of multiple global changes on the structure of microbial
      communities may be mediated by specific microbial groups with different life
      history strategies. Here, we investigated the combined effects of elevated CO2
      and N addition on soil microbial communities using PLFA profiling in a short-term
      grassland mesocosm experiment. We also examined the linkages between the relative
      abundance of r- and K-strategist microorganisms and resistance of the microbial
      community structure to experimental treatments. N addition had a significant
      effect on microbial community structure, likely driven by concurrent increases in
      plant biomass and in soil labile C and N. In contrast, microbial community
      structure did not change under elevated CO2 or show significant CO2 * N
      interactions. Resistance of soil microbial community structure decreased with
      increasing fungal/bacterial ratio, but showed a positive relationship with the
      Gram-positive/Gram-negative bacterial ratio. Our findings suggest that the Gram
      positive/Gram-negative bacteria ratio may be a useful indicator of microbial
      community resistance and that K-strategist abundance may play a role in the short
      term stability of microbial communities under global change.

PMID- 28430943
TI  - Complete heart block as isolated symptom of aortic intramural haematoma.

PMID- 28430944
TI  - Plant microbial diversity is suggested as the key to future biocontrol and health
      trends.
AB  - The microbiome of plants plays a crucial role in both plant and ecosystem health.
      Rapid advances in multi-omics tools are dramatically increasing access to the
      plant microbiome and consequently to the identification of its links with
      diseases and to the control of those diseases. Recent insights reveal a close,
      often symbiotic relationship between microorganisms and plants. Microorganisms
      can stimulate germination and plant growth, prevent diseases, and promote stress
      resistance and general fitness. Plants and their associated microorganisms form a
      holobiont and have to be considered as co-evolved species assemblages consisting
      of bacterial, archaeal and diverse eukaryotic species. The beneficial interplay
      of the host and its microbiome is responsible for maintaining the health of the
      holobiont, while diseases are often correlated with microbial dysbioses.
      Microbial diversity was identified as a key factor in preventing diseases and can
      be implemented as a biomarker in plant protection strategies. Targeted and
      predictive biocontrol approaches are possible by developing microbiome-based
      solutions. Moreover, combined breeding and biocontrol strategies maintaining
      diversity and ecosystem health are required. The analysis of plant microbiome
      data has brought about a paradigm shift in our understanding of its role in
      health and disease and has substantial consequences for biocontrol and health
      issues.

PMID- 28430945
TI  - Effects of a counselling intervention to improve contraception in deprived
      neighbourhoods: a randomized controlled trial.
AB  - Background: This study aims to evaluate the effects of a community-based
      counselling intervention to improve contraception use among immigrant and native
      residents in deprived neighbourhoods. Methods: Randomized controlled trial. Women
      aged 14-49 years and men aged 14-39 years from two low-income neighbourhoods with
      high proportion of immigration in Barcelona (Catalonia, Spain) who had not
      undergone irreversible contraception and were not planning a pregnancy were
      recruited (2011-13). A culturally developed and theoretically based brief
      counselling intervention was delivered in community settings. The primary outcome
      was the consistent use of effective contraceptive methods (optimal use).
      Secondary outcomes were the incorrect use of effective methods and the use of
      less effective methods stratified by sex and migrant status. Differences within
      subgroups from baseline to the 3-month follow-up were analysed by intention to
      treat and per protocol. The effects were assessed with adjusted robust Poisson
      regressions. Results: The study enrolled and randomized 746 eligible
      participants. There were no differences between the intervention and control
      groups in demographic characteristics. Optimal use significantly increased in
      men, women, immigrants and natives in the intervention group, with no changes in
      the control group. In the intervention group, inconsistent use of effective
      methods decreased by 54.9% and that of less effective methods by 47.2%. The
      overall adjusted prevalence ratio of optimal use in the intervention group versus
      the control group was 1.138 (95% CI: 1.010-1.284). Conclusion: This brief
      counselling intervention increased the consistent use of effective contraception
      in low-income neighbourhoods with a high proportion of immigration.

PMID- 28430946
TI  - Forgotten fungi-the gut mycobiome in human health and disease.
AB  - The human body is home to a complex and diverse microbial ecosystem that plays a
      central role in host health. This includes a diversity of fungal species that is
      collectively referred to as our 'mycobiome'. Although research into the mycobiome
      is still in its infancy, its potential role in human disease is increasingly
      recognised. Here we review the existing literature available on the human
      mycobiota with an emphasis on the gut mycobiome, including how fungi interact
      with the human host and other microbes. In doing so, we provide a comprehensive
      critique of the methodologies available to research the human mycobiota as well
      as highlighting the latest research findings from mycological surveys of
      different groups of interest including infants, obese and inflammatory bowel
      disease cohorts. This in turn provides new insights and directions for future
      studies in this burgeoning research area.

PMID- 28430947
TI  - Electrocardiographic Left Ventricular Hypertrophy Predicts Cardiovascular
      Morbidity and Mortality in Hypertensive Patients: The ALLHAT Study.
AB  - BACKGROUND: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is a
      strong predictor of cardiovascular (CV) morbidity and mortality. However, the
      predictive value of ECG LVH in treated hypertensive patients remains unclear.
      METHODS: A total of 33,357 patients (aged >= 55 years) with hypertension and at
      least 1 other coronary heart disease (CHD) risk factor were randomized to
      chlorthalidone, amlodipine, or lisinopril. The outcome of the present study was
      all-cause mortality; and secondary endpoints were CHD, nonfatal myocardial
      infarction (MI), stroke, angina, heart failure (HF), and peripheral arterial
      disease. Cornell voltage criteria (S in V3 + R in aVL > 28 [men] or >22 mm
      [women]) defined ECG LVH. RESULTS: ECGs were available at baseline in 26,384
      patients. Baseline Cornell voltage LVH was present in 1,741 (7%) patients, who
      were older (67.4 vs. 66.6 years, P < 0.001), more likely to be female (74 vs.
      44%, P < 0001) with a higher systolic blood pressure (151 vs. 146 mm Hg, P <
      0.001) than patients without ECG LVH. During 5.0 +/- 1.4 years mean follow-up,
      baseline and in-study ECG LVH was significantly associated with 29 to 98%
      increased risks of all-cause mortality, MI, CHD, stroke, and HF in multivariable
      Cox analyses. CONCLUSIONS: Baseline Cornell voltage LVH is associated with
      increased CV morbidity and all-cause mortality in treated hypertensive patients
      independent of treatment modality and other CV risk factors. CLINICAL TRIALS
      REGISTRATION: Trial Number NCT00000542.

PMID- 28430949
TI  - Capturing non-local interactions by long short-term memory bidirectional
      recurrent neural networks for improving prediction of protein secondary
      structure, backbone angles, contact numbers and solvent accessibility.
AB  - Motivation: The accuracy of predicting protein local and global structural
      properties such as secondary structure and solvent accessible surface area has
      been stagnant for many years because of the challenge of accounting for non-local
      interactions between amino acid residues that are close in three-dimensional
      structural space but far from each other in their sequence positions. All
      existing machine-learning techniques relied on a sliding window of 10-20 amino
      acid residues to capture some 'short to intermediate' non-local interactions.
      Here, we employed Long Short-Term Memory (LSTM) Bidirectional Recurrent Neural
      Networks (BRNNs) which are capable of capturing long range interactions without
      using a window. Results: We showed that the application of LSTM-BRNN to the
      prediction of protein structural properties makes the most significant
      improvement for residues with the most long-range contacts (|i-j| >19) over a
      previous window-based, deep-learning method SPIDER2. Capturing long-range
      interactions allows the accuracy of three-state secondary structure prediction to
      reach 84% and the correlation coefficient between predicted and actual solvent
      accessible surface areas to reach 0.80, plus a reduction of 5%, 10%, 5% and 10%
      in the mean absolute error for backbone phi , psi , theta and tau angles,
      respectively, from SPIDER2. More significantly, 27% of 182724 40-residue models
      directly constructed from predicted C alpha atom-based theta and tau have similar
      structures to their corresponding native structures (6A RMSD or less), which is
      3% better than models built by phi and psi angles. We expect the method to be
      useful for assisting protein structure and function prediction. Availability and
      implementation: The method is available as a SPIDER3 server and standalone
      package at http://sparks-lab.org . Contact: yaoqi.zhou@griffith.edu.au or
      yuedong.yang@griffith.edu.au. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 28430948
TI  - Functional relevance of water and glycerol channels in Saccharomyces cerevisiae.
AB  - Our understanding of the functional relevance of orthodox aquaporins and
      aquaglyceroporins in Saccharomyces cerevisiae is essentially based on phenotypic
      variations obtained by expression/overexpression/deletion of these major
      intrinsic proteins in selected strains. These water/glycerol channels are
      considered crucial during various life-cycle phases, such as sporulation and
      mating and in some life processes such as rapid freeze-thaw tolerance,
      osmoregulation and phenomena associated with cell surface. Despite their putative
      functional roles not only as channels but also as sensors, their underlying
      mechanisms and their regulation are still poorly understood. In the present
      review, we summarize and discuss the physiological relevance of S. cerevisiae
      aquaporins (Aqy1 and Aqy2) and aquaglyceroporins (Fps1 and Yfl054c). In
      particular, the fact that most S. cerevisiae laboratory strains harbor genes
      coding for non-functional aquaporins, while wild and industrial strains possess
      at least one functional aquaporin, suggests that aquaporin activity is required
      for cell survival under more harsh conditions.

PMID- 28430950
TI  - Effects of dissolved oxygen concentration and iron addition on immediate-early
      gene expression of Magnetospirillum gryphiswaldense MSR-1.
AB  - We report the effects of dissolved oxygen (DO) concentration and iron addition on
      gene expression of Magnetospirillum gryphiswaldense MSR-1 cells during
      fermentations, focusing on 0.25-24 h after iron addition. The DO was strictly
      controlled at 0.5% or 5% O2, and compared with aerobic condition. Uptake of iron
      (and formation of magnetosomes) was only observed in the 0.5% O2 condition where
      there was little difference in cell growth and carbon consumption compared to the
      5% O2 condition. Quantitative reverse transcription PCR analysis showed a rapid
      (within 0.25 h) genetic response of MSR-1 cells after iron addition for all the
      genes studied, except for MgFnr (oxygen sensor gene) and fur (ferric uptake
      regulator family gene), and which in some cases was oxygen dependent. In
      particular, expression of sodB1 (superoxide dismutase gene) and feoB1 (ferrous
      transport protein B1 gene) was markedly reduced in cultures at 0.5% O2 compared
      to those at higher oxygen tensions. Moreover, expression of katG (catalase
      peroxidase gene) and feoB2 (ferrous transport protein B2 gene) was reduced
      markedly by iron addition, regardless of oxygen conditions. These data provide a
      greater understanding of molecular response of MSR-1 cells to environmental
      conditions associated with oxygen and iron metabolisms, especially relevant to
      immediate-early stage of fermentation.

PMID- 28430952
TI  - A Strategy for Helicobacter Immunohistochemistry Utilization in Pediatric
      Practice:  Insights From Morphologic and Cost-Benefit Analyses.
AB  - Objectives: Recent studies in adults have examined the utility of
      immunohistochemistry (IHC) in detecting Helicobacter in gastric biopsy specimens
      and reached differing conclusions. Dedicated cost-benefit analysis of
      Helicobacter IHC in pediatric gastric biopsy specimens has not been performed.
      Methods: From 1,955 pediatric gastric biopsies in a 1-year period, we identified
      63 Helicobacter -positive and 120 Helicobacter -negative biopsy specimens. All
      cases were scored according to the Updated Sydney System for the severity of
      inflammation. Results: We observed that pediatric Helicobacter infection was
      significantly associated with germinal center formation, active inflammation,
      oxyntic mucosa with moderate to severe chronic inflammation, and antral mucosa
      with any chronic inflammation, exclusive of mild and superficial chronic
      inflammation. At least one associated pattern was seen in each Helicobacter 
      positive biopsy specimen. In comparison with adults, pediatric Helicobacter 
      positive biopsy specimens are more likely to lack acute inflammation and more
      likely to show moderate to marked chronic inflammation. Conclusions: We recommend
      performing Helicobacter IHC on pediatric gastric biopsy specimens with any of the
      above inflammatory patterns. This approach can sensitively identify pediatric
      patients with Helicobacter gastritis, limit IHC staining to approximately 30% of
      all gastric biopsy specimens, and reduce costs by up to $55,306.90 per 1,000
      biopsy specimens.

PMID- 28430951
TI  - Evidence for a Strong Correlation Between Transcription Factor Protein Disorder
      and Organismic Complexity.
AB  - Studies of diverse phylogenetic lineages reveal that protein disorder increases
      in concert with organismic complexity but that differences nevertheless exist
      among lineages. To gain insight into this phenomenology, we analyzed all of the
      transcription factor (TF) families for which sequences are known for 17 species
      spanning bacteria, yeast, algae, land plants, and animals and for which the
      number of different cell types has been reported in the primary literature.
      Although the fraction of disordered residues in TF sequences is often moderately
      or poorly correlated with organismic complexity as gauged by cell-type number (r2
      < 0.5), an unbiased and phylogenetically broad analysis shows that organismic
      complexity is positively and strongly correlated with the total number of TFs,
      the number of their spliced variants and their total disordered residues content
      (r2 > 0.8). Furthermore, the correlation between the fraction of disordered
      residues and cell-type number becomes stronger when confined to the TF families
      participating in cell cycle, cell size, cell division, cell differentiation, or
      cell proliferation, and other important developmental processes. The data also
      indicate that evolutionarily simpler organisms allow for the detection of subtle
      differences in the conserved IDRs of TFs as well as changes in variable IDRs,
      which can influence the DNA recognition and multifunctionality of TFs through
      direct or indirect mechanisms. Although strong correlations cannot be taken as
      evidence for cause-and-effect relationships, we interpret our data to indicate
      that increasing TF disorder likely was an important factor contributing to the
      evolution of organismic complexity and not merely a concurrent unrelated effect
      of increasing organismic complexity.

PMID- 28430954
TI  - Increased Multinucleated Megakaryocytes as an Isolated Finding in Bone Marrow:  A
      Rare Finding and Its Clinical Significance.
AB  - Objectives: Multinucleated megakaryocytes are a unique morphologic form of
      megakaryocytes characterized by multiple, distinctly separated nuclei. We
      investigated whether increased multinucleated megakaryocytes (>=25%) in otherwise
      normal-appearing bone marrow were associated with the development of a
      myelodysplastic syndrome (MDS). Methods: We retrospectively reviewed the medical
      records and bone marrow biopsy specimens of patients evaluated at our institution
      from 2011 to 2015 that met all of the following criteria: (1) 25% or more
      multinucleated megakaryocytes, (2) no other dysplastic features, (3) absence of a
      myeloid neoplasm, and (4) absence of neoplastic karyotypic abnormalities.
      Results: Nine cases of 19,885 bone marrow biopsy specimens were identified. The
      indications for bone marrow examination included plasma cell neoplasm, lymphoma,
      and cytopenia(s). All patients had anemia at the time the multinucleated
      megakaryocytes were found. No patients had thrombocytopenia or neoplastic
      karyotypic abnormalities. Follow-up was available for seven patients with a
      median of 27 months (range, 7-53 months). No patients developed progressive
      cytopenias or MDS. Conclusions: Multinucleated megakaryocytes (>=25%) as an
      isolated finding in the bone marrow are a rare phenomenon. These patients do not
      appear to be at increased risk of developing progressive cytopenia(s) or MDS.
      Caution should be taken to not overdiagnose these cases as MDS.

PMID- 28430953
TI  - Gastric Proteins MUC5AC and TFF1 as Potential Diagnostic Markers of Colonic
      Sessile Serrated Adenomas/Polyps.
AB  - Objectives: A subset of colon cancers originates from sessile serrated
      adenomas/polyps (SSA/Ps). Our goal was to identify markers for SSA/Ps that could
      aid in distinguishing them from hyperplastic polyps (HPs). Methods: We performed
      immunostaining for gastric proteins MUC5AC and TFF1 in formalin-fixed, paraffin
      embedded (FFPE) samples of HPs (n = 47), SSA/Ps (n = 37), and normal colon (n =
      30). Results: Control mucosa expressed only trace amounts of MUC5AC and TFF1. HPs
      exhibited an 11.3- and 11.4-fold increase in MUC5AC and TFF1 expression confined
      to the upper segments of the crypts near the luminal surface of the polyps.
      SSA/Ps displayed on average 1.6-fold (MUC5AC, P  < .008) and 1.4-fold (TFF1, P  <
      .03) higher signal intensity for these markers than HPs, with a dramatic
      coexpression of MUC5AC and TFF1 typically occupying the entire length of the
      crypt. Immunoperoxidase results were similar to immunofluorescence staining for
      both MUC5AC and TFF1. Conclusions: Our results suggest that the analysis of
      expression of MUC5AC and TFF1 may be useful for differentiating SSA/Ps from HPs.
      We also suggest the possibility that crypt morphology may be at least partly due
      to overproduction of highly viscous gastric mucins and that these proteins may
      play a role in the serrated pathway to colon carcinogenesis.

PMID- 28430955
TI  - Measurement of Platelet Counts and Volume Using Magnesium Sulfate as an
      Anticoagulant:  Comparison of Impedance and Light-Scatter Technology.
AB  - Objectives: Magnesium sulfate (MgSO 4 ) was recently reported as an alternative
      in vitro anticoagulant in pseudo-thrombocytopenia. Its suitability as an
      anticoagulant for the determination of reliable platelet parameters is the
      subject of this study. Methods: Platelet count and mean platelet volume were
      measured in blood samples anticoagulated with EDTA and MgSO 4 and compared. The
      platelet parameters were determined by impedance (XE 5000 [Sysmex, Norderstedt,
      Germany]; DxH 800 [Beckman-Coulter, Krefeld, Germany]) and laser light-scatter
      technology (Advia 120 [Siemens Healthcare Diagnostics, Eschborn, Germany]).
      Results: MgSO 4 anticoagulation underestimated platelet counts compared with
      EDTA. Mean platelet volume (MPV) in magnesium-anticoagulated blood was lower when
      measured by impedance but higher when light-scatter technology was used. Storage
      of the differently anticoagulated blood led to differently lower platelet counts
      after 24 hours, independent of the anticoagulant. In EDTA blood, the mean
      platelet volume increased moderately when measured by impedance but markedly when
      measured by laser light scatter. In MgSO 4 -anticoagulated blood, the MPV
      increase was negligible. Conclusions: Impedance technology and magnesium
      anticoagulation might be advantageous for standardizing MPV measurements,
      although the mean platelet count is slightly underestimated by both technologies.

PMID- 28430956
TI  - Achieving High Reliability in Histology:  An Improvement Series to Reduce Errors.
AB  - Objectives: Despite sweeping medical advances in other fields, histology
      processes have by and large remained constant over the past 175 years. Patient
      label identification errors are a known liability in the laboratory and can be
      devastating, resulting in incorrect diagnoses and inappropriate treatment. The
      objective of this study was to identify vulnerable steps in the histology
      workflow and reduce the frequency of labeling errors (LEs). Methods: In this 36
      month study period, a numerical step key (SK) was developed to capture LEs. The
      two most prevalent root causes were targeted for Lean workflow redesign: manual
      slide printing and microtome cutting. The numbers and rates of LEs before and
      after interventions were compared to evaluate the effectiveness of interventions.
      Results: Following the adoption of a barcode-enabled laboratory information
      system, the error rate decreased from a baseline of 1.03% (794 errors in 76,958
      cases) to 0.28% (107 errors in 37,880 cases). After the implementation of an
      innovative ice tool box, allowing single-piece workflow for histology microtome
      cutting, the rate came down to 0.22% (119 errors in 54,342 cases). Conclusions:
      The study pointed out the importance of tracking and understanding LEs by using a
      simple numerical SK and quantified the effectiveness of two customized Lean
      interventions. Overall, a 78.64% reduction in LEs and a 35.28% reduction in time
      spent on rework have been observed since the study began.

PMID- 28430957
TI  - CD25 Expression in B Lymphoblastic Leukemia/Lymphoma Predicts
      t(9;22)(q34;q11)/Philadelphia Chromosome Translocation (Ph) and Is Associated
      With Residual Disease in Ph-Negative Patients.
AB  - Objectives: CD25 expression is associated with t(9;22)(q34;q11)/Philadelphia
      chromosome translocation (Ph); BCR-ABL1 rearrangement in B lymphoblastic
      leukemia/lymphoma (B-LL). However, the significance of CD25 expression in Ph
      negative (Ph-) B-LL regarding residual disease (RD) and genetic abnormalities is
      largely unknown. Methods: CD25 expression by flow cytometry (FC) was correlated
      with Ph status in 95 newly diagnosed B-LL patients and with RD status in day 29
      marrow measured by FC in the context of cytogenetic risk stratification in Ph-
      patients. Results: CD25 expression was greater in Ph positive (Ph+) patients
      (80%) than in Ph- patients (17%), predicting Ph+ with 80% sensitivity and 86%
      specificity. In Ph- patients, CD25 expression (in 14 patients, 16%) was
      associated with RD in the cytogenetic intermediate-risk group: detectable RD in
      50% of CD25+ patients vs 14% of CD25- patients. Interestingly, one CD25+/Ph-
      patient had a Ph-like genotype ( ZC3HAV1-ABL2 rearrangement), and another had
      dual MYC-IGH and BCL2-IGH rearrangements. Conclusions: Our findings not only
      confirm the predictive power of CD25 expression for Ph+ but also demonstrate that
      CD25 expression is associated with RD (a biomarker correlated with prognosis) in
      Ph- patients. The latter finding is likely associated with underlying molecular
      abnormalities, including Ph-like genotype.

PMID- 28430958
TI  - Survey of Institutional Policies for Provision of "CMV-Safe" Blood in Ontario.
AB  - Objectives: Debate continues on whether leukoreduction alone (LR) is sufficiently
      similar to leukoreduced cellular products drawn from cytomegalovirus (CMV)
      seronegative (SN) donors to minimize the risk of transfusion-transmitted CMV (TT
      CMV). We sought to determine the policy, inventory, and practice landscape of the
      province for TT-CMV mitigation. Methods: A web-based survey was distributed to
      hospitals in Ontario by Canadian Blood Services to collect data on their policies
      with respect to TT-CMV prevention. Results: TT-CMV mitigation practices varied by
      patient population, hospital size, and region. Smaller institutions remain
      committed to dual prevention, whereas academic hospitals favor a single-measure
      approach. Although smaller institutions attempt to align their policies with
      leadership sites, emulation is often inaccurate. The demands for SN products also
      appear to be significantly lower than the current screening practices of Canadian
      Blood Services. Conclusions: Standardization is lacking on practices to prevent
      TT-CMV. Although there are barriers to harmonizing practices, the apparent shift
      to policies acknowledging LR as a sufficient protection is likely to continue.

PMID- 28430960
TI  - Triple-site pacing for cardiac resynchronization in permanent atrial
      fibrillation: follow-up results from a prospective observational study.
AB  - Aims: Cardiac Resynchronization Therapy (CRT) is associated with a particularly
      high non-response rate in patients with atrial fibrillation (AF). We aimed to
      assess the effectiveness of triple-site (Tri-V) pacing CRT in this population.
      Methods and results: Prospective observational study of patients with permanent
      AF who underwent CRT implantation with an additional right ventricle lead in the
      outflow tract septal wall. After implantation, programming mode (Tri-V or
      biventricular pacing) was selected based on cardiac output determination.
      Patients were classified as responders if NYHA class was reduced by at least one
      level and echocardiographic ejection fraction (EF) increased >= 10%, and as super
      responders if in NYHA class I and EF >= 50%. Forty patients (93% male, mean age
      72 +/- 10 years) were included. Thirty-three were programmed in Tri-V. The
      following results pertain to this subgroup. At baseline, 58% were in NYHA class
      III and 36% NYHA class II. At 1 year follow-up, Minnesota QoL score was reduced
      (36 +/- 23 vs. 8 +/- 6; P = 0.001) and the 6MWT distance improved (384 +/- 120 m
      to 462 +/- 87 m, P = 0.003). Mean EF increased (26% +/- 8 vs. 39 +/- 10; P <
      0.001 at 6 months and 41 +/- 10; P < 0.001 at 12 months). Responder rate was 59%
      at 6 months and 79% at 12 months. Super-responder rate was 9% at 6 months and 16%
      at 12 months. One year survival free from heart failure hospitalization was
      87.9%. Conclusion: Tri-V CRT yielded higher response and super-response rates
      than usually reported for CRT in patients with permanent AF using clinical and
      remodeling criteria.

PMID- 28430961
TI  - Whether people believe that overweight is unhealthy depends on their BMI.
AB  - An online experiment with 536 participants was conducted to investigate how
      people who differ in body weight perceive scientific information on body weight
      and mortality. The results showed that individuals who were aware that they are
      overweight were more inclined to trust a study that showed that overweight
      reduces mortality (P < 0.001). This finding is relevant as the BMI-mortality
      association remains a matter of scientific and public debate and people's risk
      perceptions influences their willingness to change behaviour.

PMID- 28430959
TI  - Expression, immunogenicity and variation of iron-regulated surface protein A from
      bovine isolates of Staphylococcus aureus.
AB  - Staphylococcus aureus iron-regulated surface protein A (IsdA) is a fibrinogen and
      fibronectin adhesin that also contributes to iron sequestration and resistance to
      innate immunity. IsdA is conserved in human isolates and has been investigated as
      a human vaccine candidate. Here we report the expression of isdA, the efficacy of
      anti-IsdA responses and the existence of IsdA sequence variants from bovine
      Staphylococcus. Clinical staphylococci were obtained from US dairy farms and
      assayed by PCR for the presence and expression of isdA. isdA-positive species
      from bovines included S. aureus, S. haemolyticus and S. chromogenes. Immunoassays
      on bovine milk and serum confirmed the induction and opsonophagocytic activity of
      anti-IsdA humoral responses. The variable region of isdA was sequenced and
      protein alignments predicted the presence of two main variants consistent with
      those from human S. aureus. Mouse antibodies against one IsdA variant reduced
      staphylococcal binding to fibronectin in vitro in an isotype-dependent manner.
      Purified IsdA variants bound distinctly to fibronectin and fibrinogen. Our
      findings demonstrate that variability within the C-terminus of this adhesin
      affects immune reactivity and binding specificity, but are consistent with the
      significance of IsdA in bovine disease and relevant for vaccine development.

PMID- 28430962
TI  - ULK1 prevents cardiac dysfunction in obesity through autophagy-meditated
      regulation of lipid metabolism.
AB  - Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long
      lived cells such as cardiomyocytes. Whereas many studies support the importance
      of autophagy in the mechanisms underlying obesity-related cardiac dysfunction,
      the role of autophagy in cardiac lipid metabolism remains unclear. In the heart,
      lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates
      accumulation of fatty acids to the heart through intravascular triglyceride (TG)
      hydrolysis. Methods and results: In both genetic and dietary models of obesity,
      we observed a substantial increase in cardiac LPL protein levels without any
      change in messenger ribonucleic acid (mRNA). This was accompanied by a dramatic
      down-regulation of autophagy in the heart, as revealed by reduced levels of unc
      51 like kinase-1 (ULK1) protein. To further explore the relationship between
      cardiac LPL and autophagy, we generated cardiomyocyte-specific knockout mice for
      ulk1 (Myh6-cre/ulk1fl/fl), Lpl (Myh6-cre/Lplfl/fl), and mice with a combined
      deficiency (Myh6-cre/ulk1fl/flLplfl/fl). Similar to genetic and dietary models of
      obesity, Myh6-cre/ulk1fl/fl mice had a substantial increase in cardiac LPL
      levels. When these mice were fed a high-fat diet (HFD), they showed elevated
      cardiac TG levels and deterioration in heart function. However, with combined
      deletion of LPL and ULK1 in Myh6-cre/ulk1fl/flLplfl/fl mice, HFD feeding did not
      lead to alterations in levels of TG or diacylglycerol, or in cardiac function. To
      further elucidate the role of autophagy in cardiac lipid metabolism, we infused a
      peptide that enhanced autophagy (D-Tat-beclin1). This effectively lowered LPL
      levels at the coronary lumen by restoring autophagy in the genetic model of
      obesity. This decrease in cardiac luminal LPL was associated with a reduction in
      TG levels and recovery of cardiac function. Conclusion: These results provide
      clear evidence of the critical role of modulating cardiac LPL activity through
      autophagy-mediated proteolytic clearance as a potential novel strategy to
      overcome obesity-related cardiomyopathy.

PMID- 28430963
TI  - Integrated care for older populations and its implementation facilitators and
      barriers: A rapid scoping review.
AB  - Purpose: Inform health system improvements by summarizing components of
      integrated care in older populations. Identify key implementation barriers and
      facilitators. Data sources: A scoping review was undertaken for evidence from
      MEDLINE, the Cochrane Library, organizational websites and internet searches.
      Eligible publications included reviews, reports, individual studies and policy
      documents published from 2005 to February 2017. Study selection: Initial eligible
      documents were reviews or reports concerning integrated care approaches in
      older/frail populations. Other documents were later sourced to identify and
      contextualize implementation issues. Data extraction: Study findings and
      implementation barriers and facilitators were charted and thematically
      synthesized. Results of data synthesis: Thematic synthesis using 30 publications
      identified 8 important components for integrated care in elderly and frail
      populations: (i) care continuity/transitions; (ii) enabling policies/governance;
      (iii) shared values/goals; (iv) person-centred care; (v) multi-/inter
      disciplinary services; (vi) effective communication; (vii) case management;
      (viii) needs assessments for care and discharge planning. Intervention outcomes
      and implementation issues (barriers or facilitators) tend to depend heavily on
      the context and programme objectives. Implementation issues in four main areas
      were observed: (i) Macro-level contextual factors; (ii) Miso-level system
      organization (funding, leadership, service structure and culture); (iii) Miso
      level intervention organization (characteristics, resources and credibility) and
      (iv) Micro-level factors (shared values, engagement and communication).
      Conclusion: Improving integration in care requires many components. However,
      local barriers and facilitators need to be considered. Changes are expected to
      occur slowly and are more likely to be successful where elements of integrated
      care are well incorporated into local settings.

PMID- 28430964
TI  - MetaLIMS, a simple open-source laboratory information management system for small
      metagenomic labs.
AB  - Background: As the cost of sequencing continues to fall, smaller groups
      increasingly initiate and manage larger sequencing projects and take on the
      complexity of data storage for high volumes of samples. This has created a need
      for low-cost laboratory information management systems (LIMS) that contain
      flexible fields to accommodate the unique nature of individual labs. Many labs do
      not have a dedicated information technology position, so LIMS must also be easy
      to setup and maintain with minimal technical proficiency. MetaLIMS is a free and
      open-source web-based application available via GitHub. The focus of MetaLIMS is
      to store sample metadata prior to sequencing and analysis pipelines. Initially
      designed for environmental metagenomics labs, in addition to storing generic
      sample collection information and DNA/RNA processing information, the user can
      also add fields specific to the user's lab. MetaLIMS can also produce a basic
      sequencing submission form compatible with the proprietary Clarity LIMS system
      used by some sequencing facilities. To help ease the technical burden associated
      with web deployment, MetaLIMS options the use of commercial web hosting combined
      with MetaLIMS bash scripts for ease of setup. MetaLIMS overcomes key challenges
      common in LIMS by giving labs access to a low-cost and open-source tool that also
      has the flexibility to meet individual lab needs and an option for easy
      deployment. By making the web application open source and hosting it on GitHub,
      we hope to encourage the community to build upon MetaLIMS, making it more robust
      and tailored to the needs of more researchers.

PMID- 28430965
TI  - Nrf2 regulates the inflammatory response, including heme oxygenase-1 induction,
      by mycoplasma pneumoniae lipid-associated membrane proteins in THP-1 cells.
AB  - A series of inflammatory responses caused by Mycoplasma pneumoniae largely depend
      on the lipid-associated membrane proteins (LAMPs). Nuclear factor E2-related
      factor 2 (Nrf2), a transcription factor, is considered to be a critical modulator
      of inflammatory responses and cellular redox homeostasis. Monocytes play an
      important role in the invasion and immunity to resist pathogens. Here, we
      investigated the role of Nrf2 in the anti-inflammatory response stimulated by
      LAMPs using the human monocyte cell line THP-1. LAMPs were shown to affect the
      localization of Nrf2, and the levels of reactive oxygen species and inflammatory
      reactants, including nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines (IL
      6, IL-8), were highly elevated in LAMP-stimulated Nrf2-silenced THP-1 cells.
      Moreover, LAMPs induced the levels of mRNA and the expression of heme oxygenase-1
      (HO-1). In summary, our results demonstrated that LAMPs cause nuclear
      translocation of Nrf2, which further suppresses the expression of inflammatory
      reactants in THP-1 cells.

PMID- 28430967
TI  - Associations of unhappiness with sociodemographic factors and unhealthy
      behaviours in Chinese adolescents.
AB  - Background: Evidence on the effects of lack of physical exercise, alcohol
      drinking and smoking on happiness is limited and inconsistent. We examined the
      associations of unhappiness with sociodemographic factors and these unhealthy
      behaviours in Chinese adolescents. In a school-based survey in 2012-13 in Hong
      Kong, 45 857 secondary school students (mean age 14.8 years, 54.0% boys) reported
      their happiness level (not happy at all/not very happy/happy/very happy),
      frequency of physical exercise, alcohol drinking status, smoking status and
      sociodemographic factors. A main and a sensitivity analysis examined the
      associations of unhappiness with the study factors, treating unhappiness as a
      binary (combining 'not happy at all' and 'not very happy') and a four-level
      ordered variable, respectively. The main and the sensitivity analysis both showed
      that unhappiness was associated with older age, very poor families, non-intact
      families, more co-residing smokers, lack of physical exercise and alcohol
      drinking; current smokers were unhappier than never and ex-smokers; unhappiness
      also increased significantly with the number of unhealthy behaviours ( P for
      trend < 0.001). In Chinese adolescents, unhappiness levels were higher in those
      who had a very poor family, a non-intact family and more co-residing smokers, and
      in those who were physically inactive, drank alcohol and smoked.

PMID- 28430966
TI  - Decreased thromboembolic stroke but not atherosclerosis or vascular remodelling
      in mice with ROCK2-deficient platelets.
AB  - Aims: Rho-associated coiled-coil containing kinase (ROCK)-2 is an important
      mediator of the actin cytoskeleton. Because changes in the actin cytoskeleton are
      critical for platelet function, we hypothesized that ROCK2 in platelets will play
      important role in thrombosis and can be potentially a target for therapeutic
      intervention in thromboembolic stroke. Methods and results: We generated platelet
      specific ROCK2-deficient mice (ROCK2Plt-/-) from conditional ROCK2fl degrees x/fl
      degrees x and platelet factor (PF)-4-Cre transgenic mice. Platelets from ROCK2Plt
      /- mice were less responsive to thrombin stimulation in terms of pseudopodia
      formation, collagen adhesion, and in the formation of homotypic and heterotypic
      aggregates. This corresponded to prolonged bleeding time and delayed vascular
      occlusion following vessel injury. To determine whether these changes in platelet
      function could affect thrombotic disease, we utilized a clot-embolic model of
      ischaemic stroke. When pre-formed clots from ROCK2Plt-/- mice were injected into
      the middle cerebral artery of control mice, cerebral blood flow recovery occurred
      more rapidly, leading to decreased cerebral injury and neurological deficits,
      compared to pre-formed clots from control mice. Interestingly, pre-formed clots
      from control mice produced similar degree of cerebral injury when injected into
      control or ROCK2Plt-/- mice, suggesting that platelet ROCK2 deficiency affects
      clot formation but not propagation. Indeed, in a non-thrombotic intra-filament
      MCA occlusion model of stroke, platelet ROCK2 deletion was not protective.
      Furthermore, ROCK2Plt-/- mice exhibit similar atherosclerosis severity and
      vascular remodeling as control mice. Conclusion: These findings indicate that
      platelet ROCK2 plays important role in platelet function and thrombosis, but does
      not contribute to the pathogenesis of atherosclerosis and vascular remodeling.

PMID- 28430969
TI  - Transfemoral aortic valve replacement prior to HeartMate II left ventricular
      assist device exchange.

PMID- 28430968
TI  - Sex chromosome-dependent differential viability of human spermatozoa during
      prolonged incubation.
AB  - STUDY QUESTION: Are there significant differences in the ability of X chromosome
      bearing (X) spermatozoa and Y chromosome-bearing (Y) spermatozoa to survive
      incubation under stressful conditions? SUMMARY ANSWER: Y spermatozoa are more
      vulnerable to stress than their X counterparts depending on culture period and
      temperature, and show higher expression of apoptotic proteins. WHAT IS KNOWN
      ALREADY: The primary sex ratio is determined by there being an equal number of
      spermatozoa carrying X and Y chromosomes. This balance can be skewed by exposure
      to stressful environmental conditions such as changes in pH, pollutants or
      endocrine disruptors. However, less is known about the ability of sperm carrying
      either sex chromosome to withstand environmental stress. STUDY DESIGN, SIZE,
      DURATION: The difference in survival between X and Y spermatozoa was evaluated by
      measuring motility, viability and Y:X chromosome ratio during incubation for 5
      days, at three temperatures (4, 22 and 37 degrees C), and three pH conditions
      (6.5, 7.5 and 8.5). To identify the critical factors that determine the survival
      of X and Y bearing spermatozoa, we analysed the expression levels of apoptosis
      related proteins (Bcl, Bax and Caspase-3), as well as the extent of DNA damage
      under a subset of conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen
      samples were obtained by masturbation from normozoospermic donors after 3 days of
      sexual abstinence. Four samples with >60% motility from different donors were
      mixed to obtain sufficient semen and eliminate sampling-related bias. Data are
      presented as mean +/- SD of three independent experiments. Mean age of donors was
      28.7 +/- 3.2 years. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 58 489
      spermatozoa were scored. The viability of Y spermatozoa was lower after exposure
      to different temperatures and culture periods than that of X spermatozoa (P <
      0.05). Increased expression of apoptotic proteins in live Y spermatozoa was
      observed, despite the addition of tocopherol to the culture medium (P < 0.05).
      LIMITATIONS, REASONS FOR CAUTION: Spermatozoa were cultured in vitro during the
      treatment period. It is difficult to extrapolate the observed lifespan
      differences to spermatozoa survival in vivo. The experiments were replicated only
      three times. WIDER IMPLICATIONS OF THE FINDINGS: The prolonged survival of X
      spermatozoa under stressful conditions might lead to shifts in the ratio of male
      to-female births. STUDY FUNDING/COMPETING INTEREST(S): This study was supported
      by the National Research Foundation of Korea (NRF) grant funded by the Korean
      government (MEST) (no. NRF-2014R1A2A2A01002706). The authors declare no competing
      financial interests.

PMID- 28430970
TI  - Helicobacter pylori outer membrane vesicles inhibit human T cell responses via
      induction of monocyte COX-2 expression.
AB  - The modulation of T cell responses by Helicobacter pylori is thought to
      potentiate both H. pylori persistence and development of gastric pathologies
      including cancer. Release of outer membrane vesicles (OMV) by H. pylori provides
      a potential vehicle for modulation of the immune system. Although OMV are thought
      to have T cell suppressive activity, this has not yet been demonstrated. Their
      suppressive activity was investigated in this study using the responses of
      peripheral blood mononuclear cells (PBMC) to T cell stimuli as a readout. We
      demonstrate that addition of OMV to PBMC significantly inhibits subsequent T cell
      proliferation in a cyclo-oxygenase-2 (COX-2)-dependent manner. Addition of OMV
      did not significantly modulate PBMC apoptosis, but induced strong expression of
      COX-2 by the monocytes present and significantly increased levels of PGE2 and IL
      10. These effects were independent of vacuolating cytotoxin expression. Together,
      these findings demonstrate that OMV can suppress human T cell responses and that
      the predominant mechanism is not through a direct effect on the T cells but
      results from the induction of COX-2 expression in monocytes. This increased COX-2
      activity may modulate not only H. pylori-directed immune responses but also wider
      immune responses.

PMID- 28430971
TI  - Association between Native American-owned casinos and the prevalence of large-for
      gestational-age births.
AB  - Background: A small number of studies have used a natural experiment approach to
      examine the health impacts of increased economic resources stemming from Native
      American-owned casinos. We build on this work by examining whether casinos are
      associated with obesity-related health in utero. Methods: We examined whether
      casino openings or expansion (as proxy for increased economic resources) are
      associated with a decreased likelihood of infants being born large-for
      gestational-age (LGA), an important risk factor for childhood overweight/obesity.
      We used repeated cross-sectional data from California birth records (1987-2011)
      to assess the prevalence of LGA births among Native Americans (n = 21 011). Using
      zip code fixed-effect regression models, we compared how prevalence of LGA births
      changed in association with casino openings or expansions, while controlling for
      secular trends through the inclusion of a comparison group of Native American
      newborns in zip codes that were eligible to open or expand casinos, but did not
      do so. In sensitivity analyses, we evaluated whether there was any change in
      small-for-gestational-age births (SGA). Results: Average prevalence of LGA births
      over the period was 11%. Every one slot machine per capita increase was
      associated with a 0.13 percentage point decrease (95% confidence interval: -0.25,
      -0.01) in the prevalence of LGA births but was not associated with SGA
      prevalence. Conclusions: Casino expansion in California is associated with a
      lower prevalence of LGA births. Interpreted in combination with previous work
      showing that California casino expansions were associated with a lower body mass
      index (BMI) among schoolchildren, these results suggest that casinos are
      associated with improvement in a surrogate marker of excess adiposity. Further
      studies are needed to elucidate the mechanisms by which casinos might be
      associated with obesity-related health outcomes among Native Americans.

PMID- 28430972
TI  - Identifying Subpopulations Vulnerable to the Thyroid-Blocking Effects of
      Perchlorate and Thiocyanate.
AB  - Context: Common environmental contaminants can disrupt normal thyroid function,
      which plays essential but varying roles at different ages. Objective: To evaluate
      the relationship of perchlorate, thiocyanate, and nitrate, three sodium-iodide
      symporter (NIS) inhibitors, and thyroid function in different age-sex-stratified
      populations. Design, Setting, Participants, and Intervention: This was a cross
      sectional analysis of data from the 2009 to 2012 National Health and Nutrition
      Examination Survey evaluating the exposure to perchlorate, thiocyanate, and
      nitrate in 3151 participants aged 12 to 80. Main Outcome Measure: Blood serum
      free thyroxine (FT4) as both a continuous and categorical variable. We also
      assessed blood serum thyroid stimulating hormone. Results: Controlling for serum
      cotinine, body mass index, total daily energy consumption, race/ethnicity, and
      poverty-to-income ratio, for each log unit increase in perchlorate, FT4 decreased
      by 0.03 ng/dL in both the general population (P = 0.004) and in all women (P =
      0.005), and by 0.06 ng/dL in adolescent girls (P = 0.029), corresponding to 4%
      and 8% decreases relative to median FT4, respectively. For each log unit increase
      thiocyanate, FT4 decreased by 0.07 ng/dL in adolescent boys (P = 0.003),
      corresponding to a 9% decrease relative to median FT4, respectively. Conclusions:
      Our results indicate that adolescent boys and girls represent vulnerable
      subpopulations to the thyroid-blocking effects of NIS symporter inhibitors. These
      results suggest a valuable screening and intervention opportunity.

PMID- 28430975
TI  - Behavioral Response of the Brown Marmorated Stink Bug (Hemiptera: Pentatomidae)
      to Semiochemicals Deployed Inside and Outside Anthropogenic Structures During the
      Overwintering Period.
AB  - The brown marmorated stink bug, Halyomorpha halys (Stal), is an invasive species
      from Asia capable of causing severe agricultural damage. It can also be a
      nuisance pest when it enters and exits anthropogenic overwintering sites. In
      recent years, pheromone lures and traps for H. halys have been developed and used
      to monitor populations in field studies. To date, no study has investigated the
      applicability of these monitoring tools for use indoors by building residents
      during the overwintering period. Herein, we 1) assessed when in late winter
      (diapause) and spring (postdiapause) H. halys begins to respond to its pheromone
      (10,11-epoxy-1-bisabolen-3-ol), 2) evaluated whether pheromone-based tools can be
      used reliably for monitoring H. halys adults in unheated and heated buildings,
      and 3) elucidated the potential for indoor management using pheromone-baited
      traps. A 2-yr trapping study suggested that H. halys began to respond reliably to
      pheromone-baited traps after a critical photoperiod of 13.5 h in the spring.
      Captures before that point were not correlated with visual counts of bugs in
      buildings despite robust populations, suggesting currently available pheromone
      baited traps were ineffective for surveillance of diapausing H. halys. Finally,
      because baited traps captured only 8-20% of the adult H. halys known to be
      present per location, they were not an effective indoor management tool for
      overwintering H. halys. Our study contributes important knowledge about the
      capacity of H. halys to perceive its pheromone during overwintering, and the
      ramifications thereof for building residents with nuisance problems.

PMID- 28430974
TI  - Using transcranial magnetic stimulation of the undamaged brain to identify lesion
      sites that predict language outcome after stroke.
AB  - Transcranial magnetic stimulation focused on either the left anterior
      supramarginal gyrus or opercular part of the left inferior frontal gyrus has been
      reported to transiently impair the ability to perform phonological more than
      semantic tasks. Here we tested whether phonological processing abilities were
      also impaired following lesions to these regions in right-handed, English
      speaking adults, who were investigated at least 1 year after a left-hemisphere
      stroke. When our regions of interest were limited to 0.5 cm3 of grey matter
      centred around sites that had been identified with transcranial magnetic
      stimulation-based functional localization, phonological impairments were observed
      in 74% (40/54) of patients with damage to the regions and 21% (21/100) of
      patients sparing these regions. This classification accuracy was better than that
      observed when using regions of interest centred on activation sites in previous
      functional magnetic resonance imaging studies of phonological processing, or
      transcranial magnetic stimulation sites that did not use functional localization.
      New regions of interest were generated by redefining the borders of each of the
      transcranial magnetic stimulation sites to include areas that were consistently
      damaged in the patients with phonological impairments. This increased the
      incidence of phonological impairments in the presence of damage to 85% (46/54)
      and also reduced the incidence of phonological impairments in the absence of
      damage to 15% (15/100). The difference in phonological processing abilities
      between those with and without damage to these 'transcranial magnetic stimulation
      guided' regions remained highly significant even after controlling for the effect
      of lesion size. The classification accuracy of the transcranial magnetic
      stimulation-guided regions was validated in a second sample of 108 patients and
      found to be better than that for (i) functional magnetic resonance imaging-guided
      regions; (ii) a region identified from an unguided lesion overlap map; and (iii)
      a region identified from voxel-based lesion-symptom mapping. Finally, consistent
      with prior findings from functional imaging and transcranial magnetic stimulation
      in healthy participants, we show how damage to our transcranial magnetic
      stimulation-guided regions affected performance on phonologically more than
      semantically demanding tasks. The observation that phonological processing
      abilities were impaired years after the stroke, suggests that other brain regions
      were not able to fully compensate for the contribution that the transcranial
      magnetic stimulation-guided regions make to language tasks. More generally, our
      novel transcranial magnetic stimulation-guided lesion-deficit mapping approach
      shows how non-invasive stimulation of the healthy brain can be used to guide the
      identification of regions where brain damage is likely to cause persistent
      behavioural effects.

PMID- 28430976
TI  - Acute and Chronic Noradrenergic Effects on Cortical Excitability in Healthy
      Humans.
AB  - Background: Noradrenaline is a major neuromodulator in the central nervous
      system, and it is involved in the pathophysiology of diverse neuropsychiatric
      diseases. Previous transcranial magnetic stimulation studies suggested that acute
      application of selective noradrenaline reuptake inhibitors enhances cortical
      excitability in the human brain. However, other, such like clinical effects,
      usually require prolonged noradrenaline reuptake inhibitor treatment, which might
      go along with different physiological effects. Methods: The purpose of this study
      was to investigate the acute and chronic effects of the selective noradrenaline
      reuptake inhibitor reboxetine on cortical excitability in healthy humans in a
      double-blind, placebo-controlled, randomized crossover study. Sixteen subjects
      were assessed with different transcranial magnetic stimulation measurements:
      motor thresholds, input-output curve, short-latency intracortical inhibition and
      intracortical facilitation, I-wave facilitation, and short-interval afferent
      inhibition before and after placebo or reboxetine (8 mg) single-dose
      administration. Afterwards, the same subjects took reboxetine (8 mg/d)
      consecutively for 21 days. During this period (subjects underwent 2 experimental
      sessions with identical transcranial magnetic stimulation measures under placebo
      or reboxetine), transcranial magnetic stimulation measurements were assessed
      before and after drug intake. Results: Both single-dose and chronic
      administration of reboxetine increased cortical excitability; increased the slope
      of the input-output curve, intracortical facilitation, and I-wave facilitation;
      but decreased short-latency intracortical inhibition and short-interval afferent
      inhibition. Moreover, chronic reboxetine showed a larger enhancement of
      intracortical facilitation and I-wave facilitation compared with single-dose
      application. Conclusions: The results show physiological mechanisms of
      noradrenergic enhancement possibly underlying the functional effects of
      reboxetine regarding acute and chronic application.

PMID- 28430977
TI  - Deep mining heterogeneous networks of biomedical linked data to predict novel
      drug-target associations.
AB  - Motivation: A heterogeneous network topology possessing abundant interactions
      between biomedical entities has yet to be utilized in similarity-based methods
      for predicting drug-target associations based on the array of varying features of
      drugs and their targets. Deep learning reveals features of vertices of a large
      network that can be adapted in accommodating the similarity-based solutions to
      provide a flexible method of drug-target prediction. Results: We propose a
      similarity-based drug-target prediction method that enhances existing association
      discovery methods by using a topology-based similarity measure. DeepWalk, a deep
      learning method, is adopted in this study to calculate the similarities within
      Linked Tripartite Network (LTN), a heterogeneous network generated from
      biomedical linked datasets. This proposed method shows promising results for drug
      target association prediction: 98.96% AUC ROC score with a 10-fold cross
      validation and 99.25% AUC ROC score with a Monte Carlo cross-validation with LTN.
      By utilizing DeepWalk, we demonstrate that: (i) this method outperforms other
      existing topology-based similarity computation methods, (ii) the performance is
      better for tripartite than with bipartite networks and (iii) the measure of
      similarity using network topology outperforms the ones derived from chemical
      structure (drugs) or genomic sequence (targets). Our proposed methodology proves
      to be capable of providing a promising solution for drug-target prediction based
      on topological similarity with a heterogeneous network, and may be readily re
      purposed and adapted in the existing of similarity-based methodologies.
      Availability and Implementation: The proposed method has been developed in JAVA
      and it is available, along with the data at the following URL:
      https://github.com/zongnansu1982/drug-target-prediction . Contact:
      nazong@ucsd.edu. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 28430973
TI  - Biological functions of fucose in mammals.
AB  - Fucose is a 6-deoxy hexose in the l-configuration found in a large variety of
      different organisms. In mammals, fucose is incorporated into N-glycans, O-glycans
      and glycolipids by 13 fucosyltransferases, all of which utilize the nucleotide
      charged form, GDP-fucose, to modify targets. Three of the fucosyltransferases,
      FUT8, FUT12/POFUT1 and FUT13/POFUT2, are essential for proper development in
      mice. Fucose modifications have also been implicated in many other biological
      functions including immunity and cancer. Congenital mutations of a Golgi
      apparatus localized GDP-fucose transporter causes leukocyte adhesion deficiency
      type II, which results in severe developmental and immune deficiencies,
      highlighting the important role fucose plays in these processes. Additionally,
      changes in levels of fucosylated proteins have proven as useful tools for
      determining cancer diagnosis and prognosis. Chemically modified fucose analogs
      can be used to alter many of these fucose dependent processes or as tools to
      better understand them. In this review, we summarize the known roles of fucose in
      mammalian physiology and pathophysiology. Additionally, we discuss recent
      therapeutic advances for cancer and other diseases that are a direct result of
      our improved understanding of the role that fucose plays in these systems.

PMID- 28430978
TI  - Culture matters: indigenizing patient safety in Bhutan.
AB  - Studies show that if quality of healthcare in a country is to be achieved, due
      consideration must be given to the importance of the core cultural values as a
      critical factor in improving patient safety outcomes. The influence of Bhutan's
      traditional (core) cultural values on the attitudes and behaviours of healthcare
      professionals regarding patient care are not known. This study aimed to explore
      the possible influence of Bhutan's traditional cultural values on staff attitudes
      towards patient safety and quality care. Undertaken as a qualitative exploratory
      descriptive inquiry, a purposeful sample of 94 healthcare professionals and
      managers were recruited from three levels of hospitals, a training institute and
      the Ministry of Health. Interviews were transcribed verbatim and analysed using
      thematic analysis strategies. The findings of the study suggest that Bhutanese
      traditional cultural values have both productive and counterproductive influences
      on staff attitudes towards healthcare delivery and the processes that need to be
      in place to ensure patient safety. Productive influences encompassed: karmic
      incentives to avoid preventable harm and promote safe patient care; and the
      prospective adoption of the 'four harmonious friends' as a culturally meaningful
      frame for improving understanding of the role and importance of teamwork in
      enhancing patient safety. Counterproductive influences included: the adoption of
      hierarchical and authoritative styles of management; unilateral decision-making;
      the legitimization of karmic beliefs; differential treatment of patients; and
      preferences for traditional healing practices and rituals. Although problematic
      in some areas, Bhutan's traditional cultural values could be used positively to
      inform and frame an effective model for improving patient safety in Bhutan's
      hospitals. Such a model must entail the institution of an 'indigenized' patient
      safety program, with patient safety research and reporting systems framed around
      local patient safety concerns and solutions, including religious and cultural
      concepts, values and perspectives.

PMID- 28430979
TI  - Effect of Physical Exercise and Acute Escitalopram on the Excitability of Brain
      Monoamine Neurons: In Vivo Electrophysiological Study in Rats.
AB  - Background: The antidepressant effect of physical exercise has been reported in
      several clinical and animal studies. Since serotonin, norepinephrine, and
      dopamine play a central role in depression, it is possible that the beneficial
      effects of physical exercise are mediated via monoamine pathways. This study
      investigates the effects of voluntary wheel running on the excitability of
      monoamine neurons. Materials and Methods: Male Sprague-Dawley rats were used in
      the study. Voluntary wheel running (VWR) rats were housed in individual cages
      with free access to a running wheel, while control animals were housed in
      standard laboratory cages. After three weeks, the rats were anesthetized, and in
      vivo electrophysiological recordings were taken from dorsal raphe nucleus
      serotonin neurons, locus coeruleus norepinephrine neurons, and ventral tegmental
      dopamine neurons. Results: VWR stimulated activity in serotonin, but not in
      norepinephrine or dopamine neurons. Subsequently, acute administration of the
      selective serotonin reuptake inhibitor escitalopram in control rats led to
      complete suppression of serotonin neurons; this suppression was reversed by
      subsequent administration of selective antagonist of serotonin-1A receptors,
      WAY100135. Escitalopram induced only partial inhibition of serotonin neurons in
      the VWR rats while WAY100135 increased the firing activity of serotonin neurons
      above the baseline value. Conclusions: The beneficial effect of physical exercise
      on mood is mediated, at least in part, via activation of serotonin neurons.
      Physical exercise can potentiate the response to selective serotonin reuptake
      inhibitors by increasing the basal firing activity and diminishing selective
      serotonin reuptake inhibitor-induced inhibition of serotonin neurons.

PMID- 28430980
TI  - The Relationship between Symptom Relief and Psychosocial Functional Improvement
      during Acute Electroconvulsive Therapy for Patients with Major Depressive
      Disorder.
AB  - Background: We aimed to compare the degree of symptom relief to psychosocial
      functional (abbreviated as "functional") improvement and explore the
      relationships between symptom relief and functional improvement during acute
      electroconvulsive therapy for patients with major depressive disorder. Methods:
      Major depressive disorder inpatients (n=130) requiring electroconvulsive therapy
      were recruited. Electroconvulsive therapy was generally performed for a maximum
      of 12 treatments. Symptom severity, using the 17-item Hamilton Depression Rating
      Scale, and psychosocial functioning (abbreviated as "functioning"), using the
      Modified Work and Social Adjustment Scale, were assessed before electroconvulsive
      therapy, after every 3 electroconvulsive therapy treatments, and after the final
      electroconvulsive therapy. Both 17-item Hamilton Depression Rating Scale and
      Modified Work and Social Adjustment Scale scores were converted to T-score units
      to compare the degrees of changes between depressive symptoms and functioning
      after electroconvulsive therapy. Structural equation modeling was used to test
      the relationships between 17-item Hamilton Depression Rating Scale and Modified
      Work and Social Adjustment Scale during acute electroconvulsive therapy. Results:
      One hundred sixteen patients who completed at least the first 3 electroconvulsive
      therapy treatments entered the analysis. Reduction of 17-item Hamilton Depression
      Rating Scale T-scores was significantly greater than that of Modified Work and
      Social Adjustment Scale T-scores at assessments 2, 3, 4, and 5. The model
      analyzed by structural equation modeling satisfied all indices of goodness-of-fit
      (chi-square = 32.882, P =.107, TLI = 0.92, CFI = 0.984, RMSEA = 0.057). The 17
      item Hamilton Depression Rating Scale change did not predict subsequent Modified
      Work and Social Adjustment Scale change. Conclusions: Functioning improved less
      than depressive symptoms during acute electroconvulsive therapy. Symptom
      reduction did not predict subsequent functional improvement. Depressive symptoms
      and functional impairment are distinct domains and should be assessed
      independently to accurately reflect the effectiveness of electroconvulsive
      therapy.

PMID- 28430981
TI  - Central Nervous System GLP-1 Receptors Regulate Islet Hormone Secretion and
      Glucose Homeostasis in Male Rats.
AB  - The glucagon-like peptide 1 (GLP-1) system plays an important role in blood
      glucose regulation, in great part through coordinate control of insulin and
      glucagon secretion. These effects are generally attributed to GLP-1 produced in
      peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain
      neurons that signal through GLP-1 receptors (GLP-1rs) expressed in brain regions
      involved in metabolic regulation. GLP-1 in the central nervous system (CNS)
      induces satiety, visceral illness, and stress responses. However, recent evidence
      suggests CNS GLP-1 is also involved in glucose regulation. To test the hypothesis
      that central GLP-1 regulates islet hormone secretion, conscious rats were given
      intracerebroventricular (ICV) GLP-1, GLP-1r antagonist exendin-[9-39] (Ex-9), or
      saline during fasting or hyperglycemia from intravenous glucose. Administration
      of CNS GLP-1 increased fasting glucose, glucagon, corticosterone, and epinephrine
      and blunted insulin secretion in response to hyperglycemia. Paradoxically, GLP-1r
      blockade with ICV Ex-9 also reduced glucose-stimulated insulin secretion, and
      administration of ICV Ex-9 to freely feeding rats caused mild glucose
      intolerance. Thus, direct administration of CNS GLP-1 affected islet hormone
      secretion counter to what is seen with peripherally administered GLP-1, an effect
      likely due to stimulation of sympathetic nervous system activity. In contrast,
      blockade of brain GLP-1r supports a role for CNS GLP-1 on glucose-stimulated
      insulin secretion and glucose control after a meal. These findings suggest a
      model in which activation of CNS GLP-1r by endogenous peptide promotes glucose
      tolerance, an effect that can be overridden by stress responses stimulated by
      exogenous GLP-1.

PMID- 28430982
TI  - Evidence of nuclei-encoded spliceosome mediating splicing of mitochondrial RNA.
AB  - Mitochondria are thought to have originated as free-living prokaryotes.
      Mitochondria organelles have small circular genomes with substantial structural
      and genetic similarity to bacteria. Contrary to the prevailing concept of
      intronless mitochondria, here we present evidence that mitochondrial RNA
      transcripts (mtRNA) are not limited to policystronic molecules, but also
      processed as nuclei-like transcripts that are differentially spliced and
      expressed in a cell-type specific manner. The presence of canonical splice sites
      in the mtRNA introns and of core components of the nuclei-encoded spliceosome
      machinery within the mitochondrial organelle suggest that nuclei-encoded
      spliceosome can mediate splicing of mtRNA.

PMID- 28430983
TI  - Absence of Endothelial ERalpha Results in Arterial Remodeling and Decreased
      Stiffness in Western Diet-Fed Male Mice.
AB  - The role of estrogen receptor-alpha (ERalpha) signaling in the vasculature of
      females has been described under different experimental conditions and our group
      recently reported that lack of endothelial cell (EC) ERalpha in female mice fed a
      Western diet (WD) results in amelioration of vascular stiffness. Conversely, the
      role of ERalpha in the male vasculature in this setting has not been explored. In
      conditions of overnutrition and insulin resistance, augmented arterial stiffness,
      endothelial dysfunction, and arterial remodeling contribute to the development of
      cardiovascular disease. Here, we used a rodent model of decreased ERalpha
      expression in ECs [endothelial cell estrogen receptor-alpha knockout (EC
      ERalphaKO)] to test the hypothesis that, similar to our findings in females, loss
      of ERalpha signaling in the endothelium of insulin-resistant males would result
      in decreased arterial stiffness. EC-ERalphaKO male mice and same-sex littermates
      were fed a WD (high in fructose and fat) for 20 weeks and then assessed for
      vascular function and stiffness. EC-ERalphaKO mice were heavier than littermates
      but exhibited decreased vascular stiffness without differences in endothelial
      dependent vasodilatory responses. Mesenteric arteries from EC-ERalphaKO mice had
      significantly increased diameters, wall cross-sectional areas, and mean wall
      thicknesses, indicative of outward hypertrophic remodeling. This remodeling
      paralleled an increased vessel wall content of collagen and elastin, inhibition
      of matrix metalloproteinase activation and a decrease of the incremental modulus
      of elasticity. In addition, internal elastic lamina fenestrae were more abundant
      in the EC-ERalphaKO mice. In conclusion, loss of endothelial ERalpha reduces
      vascular stiffness in male mice fed a WD with an associated outward hypertrophic
      remodeling of resistance arteries.

PMID- 28430984
TI  - Adjunctive use of anticoagulants at the time of percutaneous coronary
      intervention in patients with an acute coronary syndrome treated with
      fondaparinux: a multinational retrospective review.
AB  - Aim: This retrospective chart review was designed to evaluate physician adherence
      to the prescribing information for fondaparinux regarding adjunctive
      anticoagulant use during percutaneous coronary intervention (PCI) in patients
      with an acute coronary syndrome (ACS). Methods and results: Medical record
      abstractors at each site obtained information regarding the use of fondaparinux
      and adjunctive anticoagulants during PCI. Physician adherence to fondaparinux
      prescribing information regarding the administration of an adjunctive
      anticoagulant during PCI was estimated using generalized estimating equations.
      This retrospective study, conducted in 2008-2010, included a total of 1056
      patient records from 27 sites across 6 countries (Canada, France, Germany,
      Greece, Poland, and Sweden). Over 98% of patients had been treated with
      fondaparinux at the recommended 2.5 mg dose. Use of adjunctive anticoagulant
      during PCI was 97.5%, giving an adjusted adherence rate of 98.8% (95% confidence
      interval: 0.97-0.99), with 86.3% of patients receiving unfractionated heparin.
      Although the sub-group of patients with ST-elevation myocardial infarction who
      underwent primary PCI was too small to make a definitive conclusion, 70.4% of the
      159 patients did not receive fondaparinux immediately prior to (<24 h) or during
      primary PCI, suggesting that their treating physicians may have been adherent to
      the prescribing information. Conclusion: Physician adherence to the prescribing
      information for adjunctive anticoagulation during PCI in patients with an ACS
      receiving fondaparinux was high. The results were consistent in each of the six
      countries and across patient sub-groups.

PMID- 28430985
TI  - Arabidopsis CP12 mutants have reduced levels of phosphoribulokinase and impaired
      function of the Calvin-Benson cycle.
AB  - CP12 is a small, redox-sensitive protein, the most detailed understanding of
      which is the thioredoxin-mediated regulation of the Calvin-Benson cycle, where it
      facilitates the formation of a complex between glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and phosphoribulokinase (PRK) in response to changes in
      light intensity. In most organisms, CP12 proteins are encoded by small multigene
      families, where the importance of each individual CP12 gene in vivo has not yet
      been reported. We used Arabidopsis thaliana T-DNA mutants and RNAi transgenic
      lines with reduced levels of CP12 transcript to determine the relative importance
      of each of the CP12 genes. We found that single cp12-1, cp12-2, and cp12-3
      mutants do not develop a severe photosynthetic or growth phenotype. In contrast,
      reductions of both CP12-1 and CP12-2 transcripts lead to reductions in
      photosynthetic capacity and to slower growth and reduced seed yield. No clear
      phenotype for CP12-3 was evident. Additionally, the levels of PRK protein are
      reduced in the cp12-1, cp12-1/2, and multiple mutants. Our results suggest that
      there is functional redundancy between CP12-1 and CP12-2 in Arabidopsis where
      these proteins have a role in determining the level of PRK in mature leaves and
      hence photosynthetic capacity.

PMID- 28430986
TI  - Field Trial Performance of Herculex XTRA (Cry34Ab1/Cry35Ab1) and SmartStax
      (Cry34Ab1/Cry35Ab1 + Cry3Bb1) Hybrids and Soil Insecticides Against Western and
      Northern Corn Rootworms (Coleoptera: Chrysomelidae).
AB  - Western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera:
      Chrysomelidae), and northern corn rootworm, Diabrotica barberi Smith and Lawrence
      (Coleoptera: Chrysomelidae), are important insect pests in corn, Zea mays L. For
      more than a decade, growers have been using transgenic plants expressing proteins
      from the bacterium Bacillus thuringiensis (Bt) to protect corn roots from
      feeding. In 2011, western corn rootworm populations were reported to have
      developed resistance to Bt hybrids expressing Cry3Bb1 and later found to be cross
      resistant to hybrids expressing mCry3A and eCry3.1Ab. The identification of
      resistance to Cry3 (Cry3Bb1, mCry3A, and eCry3.1Ab) hybrids led to concerns about
      durability and efficacy of products with single traits and of products containing
      a pyramid of a Cry3 protein and the binary Bt proteins Cry34Ab1 and Cry35Ab1.
      From 2012 to 2014, 43 field trials were conducted across the central United
      States to estimate root protection provided by plants expressing
      Cry34Ab1/Cry35Ab1 alone (Herculex RW) or pyramided with Cry3Bb1 (SmartStax).
      These technologies were evaluated with and without soil-applied insecticides to
      determine if additional management measures provided benefit where Cry3
      performance was reduced. Trials were categorized for analysis based on rootworm
      damage levels on Cry3-expressing hybrids and rootworm feeding pressure within
      each trial. Across scenarios, Cry34Ab1/Cry35Ab1 hybrids provided excellent root
      protection. Pyramided traits provided greater root and yield protection than non
      Bt plus a soil-applied insecticide, and only in trials where larval feeding
      pressure exceeded two nodes of damage did Cry34Ab1/Cry35Ab1 single-trait hybrids
      and pyramided hybrids show greater root protection from the addition of soil
      applied insecticides.

PMID- 28430987
TI  - Rab32 subfamily small GTPases: pleiotropic Rabs in endosomal trafficking.
AB  - Rab small GTPases, well-known regulators of membrane trafficking pathways in
      eukaryotic cells, comprise approximately 60 different members in mammals. During
      the past decade, our understanding of the functions of mammalian Rab32 subfamily
      members (Rab32 and Rab38) have deepened, especially on the biogenesis of lysosome
      related organelles, such as melanosomes, and the protection mechanisms against
      several pathogenic microbial infections. Endosome-mediated membrane trafficking
      by Rab32 subfamily members plays pivotal roles in these events. In this review,
      we provide an overview of the regulatory mechanisms of mammalian Rab32-family
      members in endosomal trafficking, especially focusing on their GEF, GAP and
      effector molecules, and describe the latest findings on physiological and
      pathological functions regulated by these molecules.

PMID- 28430988
TI  - Prognostic significance of surgical extranodal extension in head and neck
      squamous cell carcinoma patients.
AB  - Background: Lymph node metastasis with extranodal extension represents one of the
      most important adverse prognostic factors for survival in patients with head and
      neck squamous cell carcinoma. We propose that extranodal extension occurs to
      differing extents. The aim of this study was to determine the prognostic
      significance of extranodal extension in patients with head and neck squamous cell
      carcinoma. Methods: Two hundred and ninety-eight patients with head and neck
      squamous cell carcinoma who underwent surgical resection and neck dissection were
      included. Cervical lymph nodes were classified into four categories: (i)
      pathological N negative, (ii) extranodal extension negative, (iii) non-surgical
      extranodal extension and (iv) surgical extranodal extension. Results: Lymph node
      metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and
      52.7% of oral cancer patients. The 3-year disease-specific survival rates for
      patients in the pathological N negative, extranodal extension negative, non
      surgical extranodal extension and surgical extranodal extension groups were
      90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer
      patients, surgical extranodal extension was associated with a significantly
      poorer disease-specific survival than a pathological N negative, extranodal
      extension negative or non-surgical extranodal extension status. In oral cancer
      patients, no significant differences were observed between the non-surgical and
      surgical extranodal extension groups. However, non-surgical extranodal extension
      was associated with a poorer disease-specific survival than a pathological N
      negative or extranodal extension negative status. Conclusions: Surgical
      extranodal extension was a poor prognostic factor in patients with head and neck
      squamous cell carcinoma. The prognostic significance of surgical extranodal
      extension differed between laryngeal/hypopharyngeal and oral cancer patients. The
      clinical significance of surgical extranodal extension was much greater for
      patients with laryngeal/hypopharyngeal cancer than oral cancer.

PMID- 28430989
TI  - Gene Fractionation and Function in the Ancient Subgenomes of Maize.
AB  - The maize genome experienced an ancient whole genome duplication ~10 MYA and the
      duplicate subgenomes have since experienced reciprocal gene loss such that many
      genes have returned to single-copy status. This process has not affected the
      subgenomes equally; reduced gene expression in one of the subgenomes mitigates
      the consequences of mutations and gene deletions and is thought to drive higher
      rates of fractionation. Here, we use published data to show that, in accordance
      with predictions of this model, paralogs with greater expression contribute more
      to phenotypic variation compared with their lowly expressed counterparts.
      Furthermore, paralogous genes in the least-fractionated subgenome account for a
      greater degree of phenotypic diversity than those resident on the more
      fractionated subgenome. Intriguingly, analysis of singleton genes reveals this
      difference persists even after fractionation is complete. Additionally, we show
      that the two subgenomes of maize may differ in their epigenetic profiles.

PMID- 28430991
TI  - Development toward high-resolution X-ray phase imaging.
AB  - Since the 1990s, the use of X-ray phase contrast has been extensively studied for
      imaging weakly absorbing objects consisting of low-Z elements such as biological
      soft tissues and polymers. The development of X-ray microscopy was also
      progressing during this time, although absorption contrast was only available. It
      was straightforward and important to develop phase-contrast X-ray microscopy. One
      characteristic in the development is that quantitative phase measurement is
      possible through the acquisition of phase-contrast images under a specific
      procedure, thanks to digital X-ray image detectors. Therefore, such a technique
      is called 'phase imaging' rather than phase-contrast imaging in this review.
      Highly sensitive three-dimensional phase imaging is feasible in combination with
      tomography. This article reviews the progress in X-ray phase imaging, especially
      with regards to X-ray microscopy.

PMID- 28430990
TI  - Three-dimensional dose prediction and validation with the radiobiological gamma
      index based on a relative seriality model for head-and-neck IMRT.
AB  - This study proposes a quality assurance (QA) method incorporating radiobiological
      factors based on the QUANTEC-determined tumor control probability and the normal
      tissue complication probability (NTCP) of head-and-neck intensity-modulated
      radiation therapy (HN-IMRT). Per-beam measurements were conducted for 20 cases
      using a 2D detector array. Three-dimensional predicted dose distributions within
      targets and organs at risk were reconstructed based on the per-beam QA results
      derived from differences between planned and measured doses. Under the predicted
      dose distributions, the differences between the physical and radiobiological
      gamma indices (PGI and RGI, respectively) based on the relative seriality (RS)
      model were evaluated. The NTCP values in the RS and Niemierko models were
      compared. The dose covers 98% (D98%) of the clinical target volume (CTV)
      decreased by 3.2% (P < 0.001), and the mean dose of the ipsilateral parotid
      increased by 6.3% (P < 0.001) compared with the original dose. RGI passing rates
      in the CTV and brain stem were greater than PGI ones by 5.8% (P < 0.001) and 2.0%
      (P < 0.001), respectively. The RS model's average NTCP values for the ipsilateral
      and contralateral parotids under the original dose were smaller than those of the
      Niemierko model by 9.0% (P < 0.001) and 7.0% (P < 0.001), respectively. The 3D
      predicted dose evaluation with RGI based on the RS model was introduced for QA of
      HN-IMRT, leading to dose evaluation for each organ with consideration of the
      radiobiological effect. This method constitutes a rational way to perform QA of
      HN-IMRT in clinical practice.

PMID- 28430992
TI  - Identifying practice-related factors for high-volume prescribers of antibiotics
      in Danish general practice.
AB  - Objectives: In Denmark, general practice is responsible for 75% of antibiotic
      prescribing in the primary care sector. We aimed to identify practice-related
      factors associated with high prescribers, including prescribers of critically
      important antibiotics as defined by WHO, after accounting for case mix by
      practice. Methods: We performed a nationwide register-based survey of antibiotic
      prescribing in Danish general practice from 2012 to 2013. The unit of analysis
      was the individual practice. We used multivariable regression analyses and an
      assessment of relative importance to identify practice-related factors driving
      high antibiotic prescribing rates. Results: We included 98% of general practices
      in Denmark ( n  =   1962) and identified a 10% group of high prescribers who
      accounted for 15% of total antibiotic prescriptions and 18% of critically
      important antibiotic prescriptions. Once case mix had been accounted for, the
      following practice-related factors were associated with being a high prescriber:
      lack of access to diagnostic tests in practice (C-reactive protein and urine
      culture); high use of diagnostic tests (urine culture and strep A throat test); a
      low percentage of antibiotic prescriptions issued over the phone compared with
      all antibiotic prescriptions; and a high number of consultations per 1000
      patients. We also found that a low number of consultations per 1000 patients was
      associated with a reduced likelihood of being a high prescriber of antibiotics.
      Conclusions: An apparent underuse or overuse of diagnostic tests in general
      practice as well as organizational factors were associated with high-prescribing
      practices. Furthermore, the choice of antibiotic type seemed less rational among
      high prescribers.

PMID- 28430994
TI  - Personhood and Natural Kinds: Why Cognitive Status Need Not Affect Moral Status.
AB  - Lockean accounts of personhood propose that an individual is a person just in
      case that individual is characterized by some advanced cognitive capacity. On
      these accounts, human beings with severe cognitive impairment are not persons.
      Some accept this result-I do not. In this paper, I therefore advance and defend
      an account of personhood that secures personhood for human beings who are
      cognitively impaired. On the account for which I argue, an individual is a person
      just in case that individual belongs to a natural kind that is normally
      characterized by advanced cognitive capacities. Since "human being" is just such
      a natural kind, individual human beings can be persons even when they do not
      themselves have advanced cognitive capacities. I argue, furthermore, that we have
      good reason to accept this account of personhood over rival accounts since it is
      uniquely able to accommodate the intuitive concept of an impaired person.

PMID- 28430995
TI  - Is popular radio a source of exposure to alcohol references in mid to later life?
      A content analysis.
AB  - Background: There is concern around alcohol consumption in mid to later life yet
      little understanding about what influences this behaviour. No previous research
      has explored the extent to which adults in mid to later life may be exposed to
      alcohol references in the media. This project aimed to determine the frequency of
      alcohol references on radio stations with a high proportion of listeners in mid
      to later life. Methods: Content analysis of alcohol references on four popular UK
      music-based radio stations with a high proportion of listeners aged 55-64 years
      over three time points. Results: Alcohol references occur frequently, but vary by
      time of year and type of radio station. When alcohol is mentioned its consumption
      is portrayed as the norm, without negative consequences. On three commercial
      stations, the majority of mentions came from advertising, whereas on BBC Radio 2
      nearly all references were talk-based. All adverts for direct promotion of
      alcohol were by supermarkets. Alcohol was frequently associated with
      celebrations, socializing or something to consume for its own sake. Conclusions:
      Adults in the age group 55-64 may be exposed to references to alcohol that could
      serve to reinforce norms of consumption of alcohol and promote purchases of cheap
      alcohol.

PMID- 28430993
TI  - A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant
      in DNA polymerase gamma.
AB  - Mutations in the mitochondrial DNA polymerase, POLG, are associated with a
      variety of clinical presentations, ranging from early onset fatal brain disease
      in Alpers syndrome to chronic progressive external ophthalmoplegia. The majority
      of mutations are linked with disturbances of mitochondrial DNA (mtDNA) integrity
      and maintenance. On a molecular level, depending on their location within the
      enzyme, mutations either lead to mtDNA depletion or the accumulation of multiple
      mtDNA deletions, and in some cases these molecular changes can be correlated to
      the clinical presentation. We identified a patient with a dominant p.Y955H
      mutation in POLG, presenting with a severe, early-onset multi-systemic
      mitochondrial disease with bilateral sensorineural hearing loss, cataract,
      myopathy, and liver failure. Using a combination of disease models of Drosophila
      melanogaster and in vitro biochemistry analysis, we compare the molecular
      consequences of the p.Y955H mutation to the well-documented p.Y955C mutation. We
      demonstrate that both mutations affect mtDNA replication and display a dominant
      negative effect, with the p.Y955H allele resulting in a more severe polymerase
      dysfunction.

PMID- 28430996
TI  - Asymmetric Hybridization in Cattails (Typha spp.) and Its Implications for the
      Evolutionary Maintenance of Native Typha latifolia.
AB  - Cattails (Typha spp.) have become an increasingly dominant component of wetlands
      in eastern North America and this dominance is largely attributable to the high
      frequency of Typha * glauca, the hybrid of native Typha latifolia and putatively
      introduced Typha angustifolia. Hybridization in this group is asymmetric, with T.
      angustifolia nearly always the maternal parent of F1 hybrids. However, the
      magnitude of hybrid infertility and whether mating asymmetries extend to the
      formation of advanced-generation hybrids have not been examined. We used hand
      crosses to measure seed set and germination success. We found that mating
      asymmetries extend to the formation of back-crosses, with ~0 seeds set when T.
      latifolia was pollinated by hybrid cattails. Seed set was unaffected by pollen
      source for T. * glauca or T. angustifolia. However, seed production by T.
      angustifolia was consistently high while that of T. * glauca was variable and
      when pollinated by other T. * glauca more than 75% lower than for any other
      intraspecific cross indicating reduced hybrid fertility. We used these results to
      parameterize a model of hybrid zone evolution in which mating patterns and
      fertility were governed by interactions between alleles at nuclear and
      cytoplasmic loci. The model revealed that asymmetric mating and reduced hybrid
      fertility should favor the maintenance of T. latifolia over T. angustifolia
      compared to null expectations. However, the model also indicated restrictive
      conditions for the long-term maintenance of T. latifolia within populations,
      indicating that asymmetric mating might only stall rather than prevent the
      displacement of native cattails by hybrids.

PMID- 28430997
TI  - Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and
      Mortality From Diarrhea.
AB  - In 2006, 2 rotavirus vaccines were licensed. We summarize the impact of rotavirus
      vaccination on hospitalizations and deaths from rotavirus and all-cause acute
      gastroenteritis (AGE) during the first 10 years since vaccine licensure,
      including recent evidence from countries with high child mortality. We used
      standardized guidelines (PRISMA) to identify observational evaluations of
      rotavirus vaccine impact among children <5 years of age that presented at least
      12 months of pre- and post-vaccine introduction surveillance data. We identified
      57 articles from 27 countries. Among children <5 years of age, the median
      percentage reduction in AGE hospitalizations was 38% overall and 41%, 30%, and
      46% in countries with low, medium, and high child mortality, respectively.
      Hospitalizations and emergency department visits due to rotavirus AGE were
      reduced by a median of 67% overall and 71%, 59%, and 60% in countries with low,
      medium, and high child mortality, respectively. Implementation of rotavirus
      vaccines has substantially decreased hospitalizations from rotavirus and all
      cause AGE.

PMID- 28430998
TI  - Reply to Mohamed S.A. Mohamed.

PMID- 28430999
TI  - Repurposing QuantiFERON for Detection of Neutralizing Interferon-gamma
      Autoantibodies in Patients With Nontuberculous Mycobacterial Infections.
AB  - Nontuberculous mycobacterial infections due to autoantibodies targeting
      interferon-gamma are an emerging medical problem. However, case finding is
      hampered due to highly complex diagnostic procedures not available in routine
      laboratories. We show that QuantiFERON assays can be exploited as a simple
      screening tool that may facilitate adequate and timely treatment.

PMID- 28431000
TI  - Left Brain Asymmetry of the Planum Temporale in a Nonhominid Primate: Redefining
      the Origin of Brain Specialization for Language.
AB  - The planum temporale (PT) is a critical region of the language functional network
      in the human brain showing a striking size asymmetry toward the left hemisphere.
      Historically considered as a structural landmark of the left-brain specialization
      for language, a similar anatomical bias has been described in great apes but
      never in monkeys-indicating that this brain landmark might be unique to Hominidae
      evolution. In the present in vivo magnetic resonance imaging study, we show
      clearly for the first time in a nonhominid primate species, an Old World monkey,
      a left size predominance of the PT among 96 olive baboons (Papio anubis), using
      manual delineation of this region in each individual hemisphere. This asymmetric
      distribution was quasi-identical to that found originally in humans. Such a
      finding questions the relationship between PT asymmetry and the emergence of
      language, indicating that the origin of this cerebral specialization could be
      much older than previously thought, dating back, not to the Hominidae, but rather
      to the Catarrhini evolution at the common ancestor of humans, great apes and Old
      World monkeys, 30-40 million years ago.

PMID- 28431001
TI  - Invasive aspergillosis in patients with underlying liver cirrhosis: a prospective
      cohort study.
AB  - The aim of this study was to determine the prevalence of invasive aspergillosis
      (IA) in patients with liver cirrhosis and the performance of serum galactomannan
      (GM) screening. Patients with decompensated liver cirrhosis and patients with
      compensated liver cirrhosis presenting with fever and/or respiratory symptoms
      were prospectively enrolled. All patients were screened by serum GM twice weekly
      irrespective of clinical signs and symptoms. Positive serum GM triggered work-up
      consisting of chest computed tomography and in case of pathological findings
      bronchoscopy. 150 patients were included in the study. Two (1.3%) had probable,
      one (0.7%) had possible, and 147 (98%) had no evidence of IA. Both patients with
      probable IA had compensated liver cirrhosis. Sensitivity for serum GM screening
      for probable versus no IA was 0.5 (95% CI, 0.09-0.91), specificity 0.97 (95% CI:
      0.92-0.99), negative predictive value 0.99 (95% CI, 0.96-0.99) and positive
      predictive value (PPV) 0.17 (95% CI, 0.01-0.64). PPV was 0.5 (95% CI, 0.03-0.98)
      in patients with clinical suspicion of IA. In conclusion, prevalence of IA in
      patients with liver cirrhosis seems to be low. Targeted GM testing in case of
      clinical suspicion of IA may be associated with markedly higher PPVs when
      compared to universal GM screening in patients with liver cirrhosis.

PMID- 28431002
TI  - Inappropriate sinus tachycardia in a heart transplant successfully treated with
      ivabradine.

PMID- 28431004
TI  - A giant compressive non coronary Valsalva sinus aneurysm.

PMID- 28431005
TI  - Occupational asthma caused by acrylic compounds from SHIELD surveillance (1989
      2014).
AB  - Background: Acrylic monomers (acrylates), methacrylates and cyanoacrylates all
      cause asthma by respiratory sensitization. Occupational inhalation exposures
      occur across a variety of industries including health care and dental work,
      beauty, laboratory science, assembly and plastic moulding. Aims: To examine
      notifications of occupational asthma caused by acrylic compounds from a UK-based
      regional surveillance scheme, in order to highlight prevalent exposures and
      trends in presentation. Methods: Retrospective review of all cases reported to
      the SHIELD surveillance scheme for occupational asthma, West Midlands, UK between
      1989 and 2014. Patient data were gathered on demographics, employment, asthma
      symptoms and diagnostic investigations including serum immunological testing,
      serial peak flow analysis and specific inhalation challenge tests. Descriptive
      statistics were used to illustrate worker characteristics and evidence for
      sensitization to acrylic compounds. Results: There were 20 affected patients out
      of 1790 total cases of occupational asthma (1%); all cases were confirmed by
      OASYS (Occupational Asthma SYStem) analysis of serial peak flow measurements,
      with three additional positive specific inhalation challenge tests. Three out of
      20 (15%) patients were current smokers and 11/20 (55%) were atopic. A variety of
      exposures and industries were implicated including: manufacturing, health care,
      beauty and printing and a novel presentation seen in teachers exposed to floor
      adhesives. Conclusions: This is the largest reported series of occupational
      asthma caused by acrylic compounds, which remain an important aetiological factor
      in this disease. Exposure occurs in a variety of industries, particularly in
      manufacturing and is seen with other, perhaps better recognized sensitizing
      agents such as isocyanates and epoxy resins.

PMID- 28431003
TI  - Intracoronary autologous bone marrow cell transfer after myocardial infarction:
      the BOOST-2 randomised placebo-controlled clinical trial.
AB  - Aims: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs)
      enhanced the recovery of left ventricular ejection fraction (LVEF) after ST
      segment elevation myocardial infarction (STEMI) in the randomised-controlled,
      open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs
      in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10
      centres in Germany and Norway. Methods and results: Using a multiple arm design,
      we investigated the dose-response relationship and explored whether gamma
      irradiation which eliminates the clonogenic potential of stem and progenitor
      cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153
      patients with large STEMI were randomly assigned to receive a single
      intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose
      (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 +/- 2.6 days after
      percutaneous coronary intervention (PCI) in addition to guideline-recommended
      medical treatment. Change in LVEF from baseline (before cell infusion) to 6
      months as determined by MRI was the primary endpoint. The trial is registered at
      Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 +/- 8.5% in
      the overall population. At 6 months, LVEF had increased by 3.3 percentage points
      in the control group and 4.3 percentage points in the hiBMC group. The estimated
      treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7;
      P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1;
      P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects.
      BMC transfer was safe and not associated with adverse clinical events.
      Conclusion: The BOOST-2 trial does not support the use of nucleated BMCs in
      patients with STEMI and moderately reduced LVEF treated according to current
      standards of early PCI and drug therapy.

PMID- 28431006
TI  - Regulation of oxidized platelet lipidome: implications for coronary artery
      disease.
AB  - Aims: Hyperlipidaemia enhances susceptibility to thrombosis, while platelet
      oxidixed LDL (oxLDL) binding in acute coronary syndrome (ACS) correlates with
      activation status. This study explores the platelet lipidome in symptomatic
      coronary artery disease (CAD) patients and the functional consequences of the
      chemokine CXCL12 and its receptors CXCR-4/-7 on lipid uptake in platelets.
      Methods and results: Platelet-oxLDL detected by flow cytometry was enhanced (P =
      0.04) in CAD patients, moderately correlated with platelet CXCR7 surface
      expression (rho = 0.39; P < 0.001), while inversely with CXCR4 (rho = 0.35; P <
      0.001). Platelet-oxLDL was elevated (P = 0.01) in ACS patients with angiographic
      evidence of intracoronary thrombi. Ex vivo analysis of intracoronary thrombi
      sections revealed oxLDL deposition in platelet-enriched areas verified by
      immunofluorescence confocal microscopy. LDL-oxLDL uptake enhanced reactive oxygen
      species, mitochondrial superoxide generation, intraplatelet LDL to oxLDL
      conversion, and lipid peroxidation, counteracted by SOD2-mimetic MnTMPyP.
      Lipidomic analysis revealed enhanced intraplatelet-oxidized phospholipids,
      cholesteryl esters, sphingomyelin, ceramides, di- and triacylglycerols,
      acylcarnitines in CAD patients compared with age-matched controls as ascertained
      by liquid chromatography hyphenated to high-resolution mass spectrometry. LDL
      oxLDL induced degranulation, alphaIIbbeta3-integrin activation, apoptosis,
      thrombin generation estimated by calibrated automated thrombinoscopy, and shape
      change verified by live imaging using scanning ion conductance microscopy.
      Further, LDL-oxLDL enhanced thrombus formation ex vivo and in vivo in mice
      (ferric chloride-induced carotid artery injury). LDL-oxLDL enhanced platelet
      CXCL12 release, differentially regulated CXCR4-CXCR7 surface exposure, while
      CXCL12 prompted LDL-oxLDL uptake and synergistically augmented the LDL-oxLDL
      induced pro-oxidative, thrombogenic impact on platelet function. Conclusion: An
      altered platelet lipidome might be associated with thrombotic disposition in CAD,
      a mechanism potentially regulated by CXCL12-CXCR4-CXCR7 axis.

PMID- 28431007
TI  - Letter: Surfer's Myelopathy: A Rare Form of Spinal Cord Infarction in Novice
      Surfers: A Systematic Review.

PMID- 28431008
TI  - Diabetes mellitus as the major risk factor for mucormycosis in Mexico:
      Epidemiology, diagnosis, and outcomes of reported cases.
AB  - Mucormycosis is an emerging infectious disease with high rates of associated
      mortality and morbidity. Little is known about the characteristics of
      mucormycosis or entomophthoromycosis occurring in Mexico. A search strategy was
      performed of literature published in journals found in available databases and
      theses published online at Universidad Nacional Autonoma de Mexico (UNAM) library
      website reporting clinical cases or clinical case series of mucormycosis and
      entomophthoromycosis occurring in Mexico between 1982 and 2016. Among the 418
      cases identified, 72% were diabetic patients, and sinusitis accounted for 75% of
      the reported cases. Diabetes mellitus was not a risk factor for
      entomophthoromycosis. Mortality rate was 51% (125/244). Rhizopus species were the
      most frequent isolates (59%, 148/250). Amphotericin B deoxycholate was used in
      89% of cases (204/227), while surgery and antifungal management as combined
      treatment was used in 90% (172/191). In diabetic individuals, this combined
      treatment approach was associated with a higher probability of survival (95% vs
      66%, OR = 0.1, 95% CI, 0.02-0.43' P = .002). The most common complications were
      associated with nephrotoxicity and prolonged hospitalization due to IV antifungal
      therapy. An algorithm is proposed to establish an early diagnosis of rhino
      orbital cerebral (ROC) mucormycosis based on standardized identification of
      warning signs and symptoms and performing an early direct microbiological exam
      and histopathological identification through a multidisciplinary medical and
      surgical team. In summary, diabetes mellitus was the most common risk factor for
      mucormycosis in Mexico; combined antifungal therapy and surgery in ROC
      mucormycosis significantly improved survival.

PMID- 28431009
TI  - Artefact-free late gadolinium enhancement imaging in patients with implanted
      cardiac devices using a modified broadband sequence: current strategies and
      results from a real-world patient cohort.
AB  - Aims: Cardiac magnetic resonance (CMR) imaging in patients with implanted cardiac
      devices is often limited by device-related imaging artefacts. Limitations can
      potentially be overcome by employing a broadband late gadolinium enhancement
      (LGE)-CMR imaging technique. The purpose of this study was to investigate the
      relationship between implanted cardiac devices and the optimal frequency offset
      on broadband LGE-CMR imaging to increase the artefact-free visibility of
      myocardial segments. Methods and results: A phantom study was performed to
      characterize magnetic field disturbances related to 15 different cardiac devices.
      This was complemented by B0 and B1+ imaging of three different device types in
      four healthy volunteers. Findings were validated in 28 patients with an
      indication for arrhythmogenic substrate characterization before catheter
      ablation. In the phantom study, the placement of a PM, implantable cardioverter
      defibrillator (ICD) or CRT-D generator led to a significant impairment of the
      radiofrequency field. B0 mapping in phantom and volunteers showed the highest off
      resonance maximum with CRT-D systems with the maximum off-resonance significantly
      decreasing for ICD or PM systems, respectively. In all patients, with
      conventional LGE imaging 73.1% (61.5-92.3%) of LV segments were free of device
      related artefacts, while with the broadband LGE technique, a significant increase
      of artefact-free segments was achieved [96.4% (85.7-100%); P = 0.00008].
      Conclusion: Using a modified broadband sequence for LGE imaging significantly
      increased the number of artefact-free myocardial segments thereby leading to
      improved diagnostic value of the CMR exam. Since the occurrence and extent of
      hyperintensity artefacts are closely related to the individual device, more
      studies are warranted to evaluate if the results can be extrapolated to other
      devices and manufacturers.

PMID- 28431011
TI  - The Relationship Between Pain Characteristics, Peer Difficulties, and Emotional
      Functioning Among Adolescents Seeking Treatment for Chronic Pain: A Test of
      Mediational Models.
AB  - Objective: To evaluate patterns of relationships between pain characteristics,
      peer difficulties, and emotional functioning in a sample of adolescents seeking
      treatment for chronic pain. Methods: Participants were 172 adolescents (age M =
      14.88 years; 76% female, 88% White) with heterogeneous chronic pain disorders who
      completed measures of pain characteristics, peer difficulties, and emotional
      functioning before their new patient appointment in a pain management clinic.
      Direct and indirect relationships between variables were tested using path
      analysis. Results: Adequate model fit was found for models that specified
      emotional functioning (anxiety and depression) as a mediator of the relationship
      between pain interference and peer difficulties. Conversely, poor fit was found
      for all models specifying peer difficulties as a mediator of the relationship
      between pain characteristics and emotional functioning. Conclusions: Assessing
      and targeting depression and anxiety among youth with high pain interference may
      help prevent or improve peer difficulties.

PMID- 28431010
TI  - Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected
      Participants on Suppressive Antiretroviral Therapy.
AB  - Background: Reversing immune exhaustion with an anti-PD-L1 antibody may improve
      human immunodeficiency virus type 1 (HIV-1)-specific immunity and increase
      clearance of HIV-1-expressing cells. Methods: We conducted a phase I, randomized,
      double-blind, placebo-controlled, dose-escalating study of BMS-936559, including
      HIV-1-infected adults aged >18 to <70 years on suppressive antiretroviral therapy
      with CD4+ counts >350 cells/MUL and detectable plasma HIV-1 RNA by single-copy
      assay. Data on single infusions of BMS-936559 (0.3 mg/kg) versus placebo are
      described. The primary outcomes were safety defined as any grade 3 or greater or
      immune-related adverse event (AE) and the change in HIV-1 Gag-specific CD8+ T
      cell responses from baseline to day 28 after infusion. Results: Eight men
      enrolled: 6 received 0.3 mg/kg of BMS-936559, and 2 received placebo infusions.
      There were no BMS-936559-related grade 3 or greater AEs. In 1 participant,
      asymptomatic hypophysitis (a protocol-defined immune-related AE) was identified
      266 days after BMS-936559 infusion; it resolved over time. The mean percentage of
      HIV-1 Gag-specific CD8+ T cells expressing interferon gamma increased from
      baseline (0.09%) through day 28 (0.20%; P = .14), driven by substantial increases
      in 2 participants who received BMS-936559. Conclusions: In this first evaluation
      of an immunologic checkpoint inhibitor in healthy HIV-1-infected persons, single
      low-dose BMS-936559 infusions appeared to enhance HIV-1-specific immunity in a
      subset of participants. Clinical Trials Registration: NCT02028403.

PMID- 28431012
TI  - Replication and repair of a reduced 2?-deoxyguanosine-abasic site interstrand
      cross-link in human cells.
AB  - Apurinic/apyrimidinic (AP) sites, or abasic sites, which are a common type of
      endogenous DNA damage, can forge interstrand DNA-DNA cross-links via reaction
      with the exocyclic amino group on a nearby 2?-deoxyguanosine or 2?-deoxyadenosine
      in the opposite strand. Here, we utilized a shuttle vector method to examine the
      efficiency and fidelity with which a reduced dG-AP cross-link-containing plasmid
      was replicated in cultured human cells. Our results showed that the cross-link
      constituted strong impediments to DNA replication in HEK293T cells, with the
      bypass efficiencies for the dG- and AP-containing strands being 40% and 20%,
      respectively. While depletion of polymerase (Pol) eta did not perturb the bypass
      efficiency of the lesion, the bypass efficiency was markedly reduced (to 1-10%)
      in the isogenic cells deficient in Pol kappa, Pol iota or Pol zeta, suggesting
      the mutual involvement of multiple translesion synthesis polymerases in bypassing
      the lesion. Additionally, replication of the cross-linked AP residue in HEK293T
      cells was moderately error-prone, inducing a total of ~26% single-nucleobase
      substitutions at the lesion site, whereas replication past the cross-linked dG
      component occurred at a mutation frequency of ~8%. Together, our results provided
      important insights into the effects of an AP-derived interstrand cross-link on
      the efficiency and accuracy of DNA replication in human cells.

PMID- 28431013
TI  - DNA double-strand break repair in Penaeus monodon is predominantly dependent on
      homologous recombination.
AB  - DNA double-strand breaks (DSBs) are mostly repaired by nonhomologous end joining
      (NHEJ) and homologous recombination (HR) in higher eukaryotes. In contrast, HR
      mediated DSB repair is the major double-strand break repair pathway in lower
      order organisms such as bacteria and yeast. Penaeus monodon, commonly known as
      black tiger shrimp, is one of the economically important crustaceans facing large
      scale mortality due to exposure to infectious diseases. The animals can also get
      exposed to chemical mutagens under the culture conditions as well as in wild.
      Although DSB repair mechanisms have been described in mammals and some
      invertebrates, its mechanism is unknown in the shrimp species. In the present
      study, we show that HR-mediated DSB repair is the predominant mode of repair in
      P. monodon. Robust repair was observed at a temperature of 30  degrees C, when 2
      ug of cell-free extract derived from hepatopancreas was used for the study.
      Although HR occurred through both reciprocal recombination and gene conversion,
      the latter was predominant when the bacterial colonies containing recombinants
      were evaluated. Unlike mammals, NHEJ-mediated DSB repair was undetectable in P.
      monodon. However, we could detect evidence for an alternative mode of NHEJ that
      uses microhomology, termed as microhomology-mediated end joining (MMEJ).
      Interestingly, unlike HR, MMEJ was predominant at lower temperatures. Therefore,
      the results suggest that, while HR is major DSB repair pathway in shrimp, MMEJ
      also plays a role in ensuring the continuity and stability of the genome.

PMID- 28431014
TI  - The draft genome of Ruellia speciosa (Beautiful Wild Petunia: Acanthaceae).
AB  - The genus Ruellia (Wild Petunias; Acanthaceae) is characterized by an enormous
      diversity of floral shapes and colours manifested among closely related species.
      Using Illumina platform, we reconstructed the draft genome of Ruellia speciosa,
      with a scaffold size of 1,021 Mb (or ~1.02 Gb) and an N50 size of 17,908 bp,
      spanning ~93% of the estimated genome (~1.1 Gb). The draft assembly predicted
      40,124 gene models and phylogenetic analyses of four key enzymes involved in
      anthocyanin colour production [flavanone 3-hydroxylase (F3H), flavonoid 3'
      hydroxylase (F3'H), flavonoid 3',5'-hydroxylase (F3'5'H), and dihydroflavonol 4
      reductase (DFR)] found that most angiosperms here sampled harboured at least one
      copy of F3H, F3'H, and DFR. In contrast, fewer than one-half (but including R.
      speciosa) harboured a copy of F3'5'H, supporting observations that blue flowers
      and/or fruits, which this enzyme is required for, are less common among flowering
      plants. Ka/Ks analyses of duplicated copies of F3'H and DFR in R. speciosa
      suggested purifying selection in the former but detected evidence of positive
      selection in the latter. The genome sequence and annotation of R. speciosa
      represents only one of only four families sequenced in the large and important
      Asterid clade of flowering plants and, as such, will facilitate extensive future
      research on this diverse group, particularly with respect to floral evolution.

PMID- 28431015
TI  - Large-scale collection of full-length cDNA and transcriptome analysis in Hevea
      brasiliensis.
AB  - Natural rubber has unique physical properties that cannot be replaced by products
      from other latex-producing plants or petrochemically produced synthetic rubbers.
      Rubber from Hevea brasiliensis is the main commercial source for this natural
      rubber that has a cis-polyisoprene configuration. For sustainable production of
      enough rubber to meet demand elucidation of the molecular mechanisms involved in
      the production of latex is vital. To this end, we firstly constructed rubber full
      length cDNA libraries of RRIM 600 cultivar and sequenced around 20,000 clones by
      the Sanger method and over 15,000 contigs by Illumina sequencer. With these data,
      we updated around 5,500 gene structures and newly annotated around 9,500
      transcription start sites. Second, to elucidate the rubber biosynthetic pathways
      and their transcriptional regulation, we carried out tissue- and cultivar
      specific RNA-Seq analysis. By using our recently published genome sequence, we
      confirmed the expression patterns of the rubber biosynthetic genes. Our data
      suggest that the cytoplasmic mevalonate (MVA) pathway is the main route for
      isoprenoid biosynthesis in latex production. In addition to the well-studied
      polymerization factors, we suggest that rubber elongation factor 8 (REF8) is a
      candidate factor in cis-polyisoprene biosynthesis. We have also identified 39
      transcription factors that may be key regulators in latex production. Expression
      profile analysis using two additional cultivars, RRIM 901 and PB 350, via an RNA
      Seq approach revealed possible expression differences between a high latex
      yielding cultivar and a disease-resistant cultivar.

PMID- 28431016
TI  - Somatic transposition and meiotically driven elimination of an active helitron
      family in Pleurotus ostreatus.
AB  - Helitrons constitute a superfamily of DNA transposons that were discovered in
      silico and are widespread in most eukaryotic genomes. They are postulated to
      mobilize through a "rolling-circle" mechanism, but the experimental evidence of
      their transposition has been described only recently. Here, we present the
      inheritance patterns of HELPO1 and HELPO2 helitron families in meiotically
      derived progeny of the basidiomycete Pleurotus ostreatus. We found distorted
      segregation patterns of HELPO2 helitrons that led to a strong under
      representation of these elements in the progeny. Further investigation of HELPO2
      flanking sites showed that gene conversion may contribute to the elimination of
      such repetitive elements in meiosis, favouring the presence of HELPO2 vacant
      loci. In addition, the analysis of HELPO2 content in a reconstructed pedigree of
      subclones maintained under different culture conditions revealed an event of
      helitron somatic transposition. Additional analyses of genome and transcriptome
      data indicated that P. ostreatus carries active RNAi machinery that could be
      involved in the control of transposable element proliferation. Our results
      provide the first evidence of helitron mobilization in the fungal kingdom and
      highlight the interaction between genome defence mechanisms and invasive DNA.

PMID- 28431017
TI  - Long non-coding RNA exchange during the oocyte-to-embryo transition in mice.

PMID- 28431018
TI  - Disulfide Bonds Enable Accelerated Protein Evolution.
AB  - The different proteins of any proteome evolve at enormously different rates. What
      factors contribute to this variability, and to what extent, is still a largely
      open question. We hypothesized that disulfide bonds, by increasing protein
      stability, should make proteins' structures relatively independent of their amino
      acid sequences, thus acting as buffers of deleterious mutations and enabling
      accelerated sequence evolution. In agreement with this hypothesis, we observed
      that membrane proteins with disulfide bonds evolved 88% faster than those without
      disulfide bonds, and that extracellular proteins with disulfide bonds evolved 49%
      faster than those without disulfide bonds. In addition, genes encoding proteins
      with disulfide bonds exhibit an increased likelihood of showing signatures of
      positive selection. Multivariate analyses indicate that the trend is independent
      of a number of potentially confounding factors. The effect, however, is not
      observed among the longest proteins, which can become stabilized by mechanisms
      other than disulfide bonds.

PMID- 28431019
TI  - Identifying Cytomegalovirus Complications Using the Quantiferon-CMV Assay After
      Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - Background: A simple test to identify recovery of CMV-specific T-cell immunity
      following hematopoietic stem cell transplantation (HSCT) could assist clinicians
      in managing CMV-related complications. Methods: In an observational, multicenter,
      prospective study of 94 HSCT recipients we evaluated CMV-specific T-cell immunity
      at baseline, 3, 6, 9, and 12 months after transplant using the Quantiferon-CMV,
      an enzyme-linked immunosorbent spot assay (ELISpot), and intracellular cytokine
      staining. Results: At 3 months after HSCT, participants who developed CMV disease
      (n = 8) compared with CMV reactivation (n = 26) or spontaneous viral control (n =
      25) had significantly lower CD8+ T-cell production of interferon-gamma (IFN
      gamma) in response to CMV antigens measured by Quantiferon-CMV (P = .0008). An
      indeterminate Quantiferon-CMV result had a positive predictive value of 83% and a
      negative predictive value of 98% for identifying participants at risk of further
      CMV reactivation. Participants experiencing CMV reactivation compared with
      patients without CMV reactivation had a reduced proportion of polyfunctional (IFN
      gamma+/tumor necrosis factor alpha-positive) CD4+ and CD8+ T cells and a higher
      proportion of interleukin 2-secreting cells (P = .01 and P = .002, respectively).
      Conclusions: Quantifying CMV-specific T-cell immunity after HSCT can identify
      participants at increased risk of clinically relevant CMV-related outcomes.

PMID- 28431020
TI  - Is it time to recognize a new phenotype? Heart failure with preserved ejection
      fraction with pulmonary vascular disease.

PMID- 28431022
TI  - Cpp1 phosphatase mediated signaling crosstalk between Hog1 and Cek1 mitogen
      activated protein kinases is involved in the phenotypic transition in Candida
      albicans.
AB  - Cellular signaling pathways involved in cell growth and differentiation mediated
      by mitogen-activated protein kinase (MAPK) cascades have been well characterized
      in fungi. However, the mechanisms of signaling crosstalk between MAPKs to ensure
      signaling specificity are largely unknown. Previous work showed that activation
      of the Candida albicans Cek1 MAPK pathway resulted in opaque cell formation and
      filamentation, which mirrored the phenotypes to hog1Delta. Additionally, deleting
      the HOG1 gene stimulated Cek1p. Thus, we hypothesized that an unknown factor
      could act as a bridge between these two MAPKs. In Saccharomyces cerevisiae, the
      dual-specificity phosphatase (DSP) Msg5 specifically dephosphorylates
      Fus3p/Kss1p. C. albicans Cpp1, an ortholog of Msg5, has been shown to be
      important in regulating Cek1p. Compared with the wild-type strain, hog1Delta
      shows a ~40% reduction in CPP1 expression. Consistent with previous reports, CPP1
      deletion also resulted in Cek1 hyperphosphorylation, implicating Cpp1 as a
      regulator of the Hog1 and Cek1 cascades. Interestingly, both cpp1Delta and
      hog1Delta induced 100% opaque colony formation in MTL-homozygous strains grown on
      N-acetylglucosamine (NAG) plates, whereas the wild-type and complemented strains
      exhibited 80.9% and 77.1% white-to-opaque switching rates, respectively. CPP1
      gene deletion also caused hyperfilamentous phenotypes in both white and opaque
      cells. These phenomena may be due to highly phosphorylated Cek1p, as deleting
      CEK1 in the cpp1Delta background generated nonfilamentous strains and reduced
      opaque colony formation. Taken together, we conclude that cpp1Delta and hog1Delta
      exhibited comparable phenotypes, and both are involved in regulating Cek1
      phosphorylation, implicating Cpp1 phosphatase as a key intermediary between the
      Hog1 and Cek1 signal transduction pathways.

PMID- 28431021
TI  - Patterns of Genome-Wide Diversity and Population Structure in the Drosophila
      athabasca Species Complex.
AB  - The Drosophila athabasca species complex contains three recently diverged,
      prezygotically isolated semispecies (Western-Northern, Eastern-A, and Eastern-B)
      that are distributed across North America and share zones of sympatry. Inferences
      based on a handful of loci suggest that this complex might be an ideal system for
      studying the genetics of incipient speciation and the evolution of prezygotic
      isolating mechanisms, but patterns of differentiation have not been characterized
      systematically. Here, we assembled a draft genome for D. athabasca and analyze
      whole-genome re-sequencing data for 28 individuals from across the species range
      to characterize genome-wide patterns of diversity and population differentiation
      among semispecies. Patterns of differentiation on the X-chromosome vs. autosomes
      vary, with the X-chromosome showing better phylogenetic resolution and increased
      levels of between semispecies divergence. Despite low levels of overall
      differentiation and a lack of phylogenetic resolution of the autosomes for the
      most closely related semispecies, individuals do exhibit distinct genetic
      clustering. Demographic analyses provide some support for a model of isolation
      with migration within D. athabasca, with divergence times <20 kya. The young
      divergence times of the semispecies of D. athabasca, together with strong levels
      of sexual isolation, makes them a promising system for studying the evolution of
      prezygotic isolation and speciation.

PMID- 28431023
TI  - Safety and Efficacy of the Sofia (6F) PLUS Distal Access Reperfusion Catheter in
      the Endovascular Treatment of Acute Ischemic Stroke.
AB  - BACKGROUND: Neuroendovascular intervention has become a key treatment option for
      acute ischemic stroke. The Sofia (6F) PLUS catheter was designed for
      neurovascular access for diagnostic or therapeutic interventions. OBJECTIVE: To
      report the first series describing use of the Sofia PLUS intermediate/distal
      access reperfusion catheter in the treatment of acute ischemic stroke. METHODS:
      In this retrospective study, 41 stroke cases were identified in which the
      catheter was utilized for thrombolysis/thrombectomy. Mean preprocedure National
      Institutes of Health Stroke Scale score was 16.5 +/- 5.2 (range 4-29). Occluded
      vessels included the M1 segment, M2 segment, internal carotid artery terminus,
      cervical internal carotid artery, and basilar artery. RESULTS: Successful
      positioning of the Sofia PLUS catheter near the occlusion site was achieved in 38
      (92.7%) of 41 cases in which thrombectomy or thrombolysis was attempted using
      intraarterial tissue plasminogen activator, a direct aspiration first-pass
      technique, and/or stent retrieval. A postprocedure thrombolysis in cerebral
      infarction (TICI) score of 2b/3 was achieved in 37 of 41 cases. Of 15 cases where
      the Sofia PLUS was used for a direct aspiration first-pass technique, TICI 2b/3
      was achieved in 11 (73.3%). In one case where intra-arterial tissue plasminogen
      activator was used as the only treatment modality, TICI 2a was achieved. No
      device-related or catheter-related complications were observed. The mean 7-d
      postprocedure National Institutes of Health Stroke Scale score among the 39
      survivors was 8.5 +/- 7.3 (range 0-23). CONCLUSION: Initial results with use of
      the Sofia (6F) PLUS for endovascular treatment of acute ischemic stroke have been
      encouraging. Experience with a larger series is warranted to further evaluate the
      safety and efficacy of this device and compare it with other reperfusion
      catheters.

PMID- 28431024
TI  - Radiosurgery for Unruptured Brain Arteriovenous Malformations: An International
      Multicenter Retrospective Cohort Study.
AB  - BACKGROUND: The role of intervention in the management of unruptured brain
      arteriovenous malformations (AVM) is controversial. OBJECTIVE: To analyze in a
      multicenter, retrospective cohort study, the outcomes following radiosurgery for
      unruptured AVMs and determine predictive factors. METHODS: We evaluated and
      pooled AVM radiosurgery data from 8 institutions participating in the
      International Gamma Knife Research Foundation. Patients with unruptured AVMs and
      >=12 mo of follow-up were included in the study cohort. Favorable outcome was
      defined as AVM obliteration, no postradiosurgical hemorrhage, and no permanently
      symptomatic radiation-induced changes. RESULTS: The unruptured AVM cohort
      comprised 938 patients with a median age of 35 yr. The median nidus volume was
      2.4 cm 3 , 71% of AVMs were located in eloquent brain areas, and the Spetzler
      Martin grade was III or higher in 57%. The median radiosurgical margin dose was
      21 Gy and follow-up was 71 mo. AVM obliteration was achieved in 65%. The annual
      postradiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation
      induced changes occurred in 9% and 3%, respectively. Favorable outcome was
      achieved in 61%. In the multivariate logistic regression analysis, smaller AVM
      maximum diameter ( P = .001), the absence of AVM-associated arterial aneurysms (
      P = .001), and higher margin dose ( P = .002) were found to be independent
      predictors of a favorable outcome. A margin dose >= 20 Gy yielded a significantly
      higher rate of favorable outcome (70% vs 36%; P < .001). CONCLUSION: Radiosurgery
      affords an acceptable risk to benefit profile for patients harboring unruptured
      AVMs. These findings justify further prospective studies comparing radiosurgical
      intervention to conservative management for unruptured AVMs.

PMID- 28431025
TI  - 1H Magnetic Resonance Spectroscopy of live human sperm.
AB  - STUDY QUESTION: Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain
      information about the molecules and metabolites in live human spermatozoa?
      SUMMARY ANSWER: Percoll-based density gradient centrifugation (DGC) followed by a
      further two washing steps, yielded enough sperm with minimal contamination
      (<0.01%) from seminal fluid to permit effective MRS which detected significant
      differences (P < 0.05) in the choline/glycerophosphocholine (GPC), lipid and
      lactate regions of the 1H MRS spectrum between sperm in the pellet and those from
      the 40%/80% interface. WHAT IS KNOWN ALREADY: Current methods to examine sperm
      are either limited in their value (e.g. semen analysis) or are destructive (e.g.
      immunohistochemistry, sperm DNA testing). A few studies have previously used MRS
      to examine sperm, but these have either looked at seminal plasma from men with
      different ejaculate qualities or at the molecules present in pooled samples of
      lyophilized sperm. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Sperm suspended in
      phosphate buffered saline (PBS) at 37 degrees C were examined by 1H MRS scanning
      using a 1H excitation-sculpting solvent suppression sequence after recovery from
      fresh ejaculates by one of three different methods: (i) simple centrifugation;
      (ii) DGC with one wash; or (iii) DGC with two washes. In the case of DGC, sperm
      were collected both from the pellet ('80%' sperm) and the 40/80 interface ('40%'
      sperm). Spectrum processing was carried out using custom Matlab scripts to
      determine; the degree of seminal plasma/Percoll contamination, the minimum sperm
      concentration for 1H MRS detection and differences between the 1H MRS spectra of
      '40%' and '80%' sperm. MAIN RESULTS AND THE ROLE OF CHANCE: DGC with two washes
      minimized the 1H MRS peak intensity for both seminal plasma and Percoll/PBS
      solution contamination while retaining sperm specific peaks. For the MRS scanner
      used in this study, the minimum sperm concentration required to produce a
      choline/GPC 1H MRS peak greater than 3:1 signal to noise ratio (SNR) was
      estimated at ~3 * 106/ml. The choline/GPC and lactate/lipid regions of the 1H
      spectrum were significantly different by two-way ANOVA analysis (P < 0.0001; n =
      20). ROC curve analysis of these region showed significant ability to distinguish
      between the two sperm populations: choline/GPC ROC AUC = 0.65-0.67, lactate/lipid
      ROC AUC = 0.86-0.87. LIMITATIONS, REASONS FOR CAUTION: Only 3-4 semen samples
      were used to assess the efficacy of each sperm washing protocol that were
      examined. The estimated minimum sperm concentration required for MRS is specific
      to the hardware used in our study and may be different in other spectrometers.
      Spectrum binning is a low resolution analysis method that sums MRS peaks within a
      chemical shift range. This can obscure the identity of which metabolite(s) are
      responsible for differences between sperm populations. Further work is required
      to determine the relative contribution of somatic cells to the MRS spectrum from
      the '40%' and '80%' sperm. WIDER IMPLICATIONS OF THE FINDINGS: 1H MRS can provide
      information about the molecules present in live human sperm and may therefore
      permit the study of the underlying functional biology or metabolomics of live
      sperm. Given the relatively low concentration of sperm required to obtain a
      suitable MRS signal (~3 * 106/ml), this could be carried out on sperm from men
      with oligo-, astheno- or teratozoospermia. This may lead to the development of
      new diagnostic tests or ultimately novel treatments for male factor infertility.
      STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by the Medical
      Research Council Grant MR/M010473/1. The authors declare no conflicts of
      interest.

PMID- 28431027
TI  - Eisenmenger syndrome: a rare malady that continues to fascinate.

PMID- 28431026
TI  - Minimally Invasive Sacroiliac Joint Fusion, Radiofrequency Denervation, and
      Conservative Management for Sacroiliac Joint Pain: 6-Year Comparative Case
      Series.
AB  - BACKGROUND: Sacroiliac joint (SIJ) pain is an under-recognized condition.
      Substantial information supports the safety and effectiveness of SIJ fusion
      (SIJF). Long-term follow-up after SIJF has not been reported. OBJECTIVE: To
      determine responses to conservative management (CM), SIJ denervation, and SIJF in
      patients with SIJ pain unresponsive to CM. METHODS: Retrospective study with long
      term (up to 6 yr) follow-up of 137 patients with SIJ pain seen in an outpatient
      neurosurgery clinic who received either CM (n = 63), sacroiliac denervation (n =
      47), or minimally invasive SIJF (n = 27). At each routine clinic visit, patients
      completed pain scores and Oswestry Disability Index. Additional data were
      extracted from medical charts. RESULTS: Patients treated with continued CM had no
      long-term improvement in pain (mean worsening of 1 point) or disability (mean
      Oswestry Disability Index worsened by 4-6 points), increased their use of
      opioids, and had poor long-term work status. SIJF patients had large improvements
      in SIJ pain (mean 6 points), large improvements in disability (mean 25 points), a
      decrease in opioid use, and good final work status. Sacroiliac denervation
      patients had intermediate responses (0-1 and 1-2 points, respectively).
      CONCLUSION: In patients with SIJ pain unresponsive to CM, SIJF resulted in
      excellent long-term clinical responses, with low opioid use and better work
      status compared to other treatments.

PMID- 28431028
TI  - Hybrid de novo genome assembly of the Chinese herbal fleabane Erigeron
      breviscapus.
AB  - Background: The plants in the Erigeron genus of the Compositae (Asteraceae)
      family are commonly called fleabanes, possibly due to the belief that certain
      chemicals in these plants repel fleas. In the traditional Chinese medicine,
      Erigeron breviscapus , which is native to China, was widely used in the treatment
      of cerebrovascular disease. A handful of bioactive compounds, including
      scutellarin, 3,5-dicaffeoylquinic acid, and 3,4-dicaffeoylquinic acid, have been
      isolated from the plant. With the purpose of finding novel medicinal compounds
      and understanding their biosynthetic pathways, we propose to sequence the genome
      of E. breviscapus . We assembled the highly heterozygous E. breviscapus genome
      using a combination of PacBio single-molecular real-time sequencing and next
      generation sequencing methods on the Illumina HiSeq platform. The final draft
      genome is approximately 1.2 Gb, with contig and scaffold N50 sizes of 18.8 kb and
      31.5 kb, respectively. Further analyses predicted 37 504 protein-coding genes in
      the E. breviscapus genome and 8172 shared gene families among Compositae species.
      The E. breviscapus genome provides a valuable resource for the investigation of
      novel bioactive compounds in this Chinese herb.

PMID- 28431029
TI  - The Chinese Version of the Brief Assessment of Cognition in Schizophrenia: Data
      of a Large-Scale Mandarin-Speaking Population.
AB  - Objective: The Brief Assessment of Cognition in Schizophrenia (BACS) is a
      cognitive assessment tool used to measure the broad aspects of cognition that are
      most frequently impaired in patients with schizophrenia. This study aims to
      develop the normative data of the Chinese version of the BACS among the Mandarin
      speaking population. Method: This cross-sectional study included 382 healthy
      participants (age range: 19-79 years; mean age: 48.0 +/- 16.7 years, 47.6% men)
      in Taiwan, who were evaluated with the BACS. Means and standard deviations of
      subtests and composite scores were arranged by age group and gender. The Z-scores
      calculated based on the U.S. norms were compared to our scores based on the norms
      established in this study. Results: The raw scores of all the BACS tests (verbal
      memory, digit sequencing, token motor test, verbal fluency, symbol coding, and
      Tower of London) were negatively correlated with participants' age. Women were
      superior to men in verbal memory, but inferior to them in executive function.
      Furthermore, applying the U.S. norms of the BACS to determine the performance of
      the Chinese BACS results in bias with regard to verbal memory, token motor test,
      verbal fluency, symbol coding, Tower of London and composite score. Conclusions:
      These findings demonstrate that directly applying western cognitive norms to a
      Mandarin-speaking population can cause biased interpretations. The results of
      this study can be an important reference for clinical settings and research
      related to cognitive assessments in Mandarin-speaking Chinese populations.

PMID- 28431030
TI  - Using Multivariate Base Rates to Interpret Low Scores on an Abbreviated Battery
      of the Delis-Kaplan Executive Function System.
AB  - Objective: Executive function consists of multiple cognitive processes that
      operate as an interactive system to produce volitional goal-oriented behavior,
      governed in large part by frontal microstructural and physiological networks.
      Identification of deficits in executive function in those with neurological or
      psychiatric conditions can be difficult because the normal variation in executive
      function test scores, in healthy adults when multiple tests are used, is largely
      unknown. This study addresses that gap in the literature by examining the
      prevalence of low scores on a brief battery of executive function tests. Method:
      The sample consisted of 1,050 healthy individuals (ages 16-89) from the
      standardization sample for the Delis-Kaplan Executive Function System (D-KEFS).
      Seven individual test scores from the Trail Making Test, Color-Word Interference
      Test, and Verbal Fluency Test were analyzed. Results: Low test scores, as defined
      by commonly used clinical cut-offs (i.e., <=25th, 16th, 9th, 5th, and 2nd
      percentiles), occurred commonly among the adult portion of the D-KEFS normative
      sample (e.g., 62.8% of the sample had one or more scores <=16th percentile, 36.1%
      had one or more scores <=5th percentile), and the prevalence of low scores
      increased with lower intelligence and fewer years of education. Conclusions: The
      multivariate base rates (BR) in this article allow clinicians to understand the
      normal frequency of low scores in the general population. By use of these BRs,
      clinicians and researchers can improve the accuracy with which they identify
      executive dysfunction in clinical groups, such as those with traumatic brain
      injury or neurodegenerative diseases.

PMID- 28431031
TI  - Sandbagging on the Immediate Post-Concussion Assessment and Cognitive Testing
      (ImPACT) in a high school athlete population.
AB  - The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a
      computerized neuropsychological test battery commonly used to assess cognitive
      functioning after a concussion. It is recommended that application of ImPACT
      utilizes a baseline administration so athletes have an individualized baseline
      with which to compare post-injury results should they sustain a concussion. It
      has been suggested that athletes may provide suboptimal effort, called
      "sandbagging," in order to return to their baseline cognitive scores, and thus to
      play, more quickly. This research examines ImPACT baseline scores when high
      school athletes were asked to attempt to "sandbag," and compares those scores
      with scores obtained when they were asked to give their "best effort." Fifty-four
      high school student athlete volunteers participated in the study. In contrast to
      previous research that just looked at the cut-score invalidity indicators built
      into ImPACT, this research developed a regression equation to predict
      sandbagging. A logistic regression equation developed with four variables that
      demonstrated the largest effect size between "best effort" and "sandbagged"
      baselines showed a 99.7% classification accuracy for the "best effort" and
      "sandbag" groups.

PMID- 28431032
TI  - Neuropsychology and Rehabilitation Services in the United States: Brief Report
      from a Survey of Clinical Neuropsychologists.
AB  - Objective: To provide a brief presentation of preliminary data on rehabilitation
      services provided by clinical neuropsychologists within the United States.
      Method: This survey utilized data extracted from a larger international research
      study conducted in 39 countries including N = 173 professionals who reported to
      engage in neuropsychological rehabilitative services within the past year (63.6%
      female, 44.36 +/- 11.83 years of age) took part in the study. Results:
      Neuropsychologists providing rehabilitation services in the United States in the
      past year were more likely to provide individual versus group therapy, likely to
      employ technology (e.g., personal computers, mobile phones/smartphones) as part
      of treatment services, see a range of diagnostic groups most prominently
      traumatic brain injury and stroke/vascular conditions, and work to address a
      range of both cognitive (e.g., memory, attention/concentration, and executive
      functioning) and psychological (e.g., emotional/behavioral adjustment and well
      being, awareness of disability/disease) issues. Conclusions: Prior published
      surveys suggest that clinical neuropsychologists have a growing involvement in
      rehabilitation services within the United States but with little clarity as to
      the actual characteristics of actual professional activities and practices. The
      present study aimed to provide such information and hopefully will be helpful in
      promoting additional systematic studies in this area.

PMID- 28431033
TI  - Emotional Intelligence in Agenesis of the Corpus Callosum.
AB  - People with agenesis of the corpus callosum (AgCC) with normal general
      intelligence have deficits in complex cognitive processing, as well as in social
      cognition. It is uncertain the extent to which impoverished processing of
      emotions may contribute to social processing deficiencies. We used the Mayer
      Salovey-Caruso Emotional Intelligence Test to clarify the nature of emotional
      intelligence in 16 adults with AgCC. As hypothesized, persons with AgCC exhibited
      greater disparities from norms on tests involving more socially complex aspects
      of emotions. The AgCC group did not differ from norms on the Experiential
      subscale, but they were significantly below norms on the Strategic subscale.
      These findings suggest that the corpus callosum is not essential for experiencing
      and thinking about basic emotions in a "normal" way, but is necessary for more
      complex processes involving emotions in the context of social interactions.

PMID- 28431034
TI  - Effects of Sleep Loss on Subjective Complaints and Objective Neurocognitive
      Performance as Measured by the Immediate Post-Concussion Assessment and Cognitive
      Testing.
AB  - Objective: This study examined the effects of total and partial sleep deprivation
      on subjective symptoms and objective neurocognitive performance, as measured by
      the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) in a
      sample of healthy adults. Method: One-hundred and two, right-handed, healthy
      participants (between ages 18 and 30 years old) completed three consecutive
      nights in the sleep laboratory with concurrent continuous polysomnography
      monitoring. Night 1 served as a baseline night. Prior to Night 2, they were
      randomly assigned to one of three sleep conditions: undisrupted normal sleep (N =
      34), sleep restriction (50% of habitual sleep, N = 37), or total sleep
      deprivation (N = 31). Participants slept undisturbed on Night 3. ImPACT was
      administered on three separate occasions. Results: Sleep loss was associated with
      increased severity of subjectively reported affective, cognitive, physical, and
      sleep symptoms. Although objective neurocognitive task scores derived from the
      ImPACT battery did not corroborate subjective complaints, sleep loss was
      associated with significant differences on tasks of visual memory, reaction time,
      and visual motor speed over time. Conclusions: While self-report measures
      suggested marked impairments following sleep loss, deficits in neurocognitive
      performance were observed only on three domains measured with ImPACT. ImPACT may
      capture subtle changes in neurocognitive performance following sleep loss;
      however, independent and larger validation studies are needed to determine its
      sensitivity to acute sleep loss and recovery sleep. Neurocognitive screening
      batteries may be useful for detecting the effects of more severe or chronic sleep
      loss under high-stress conditions that mimic high-risk occupations.

PMID- 28431035
TI  - Medical Symptom Validity Test Performance Following Moderate-Severe Traumatic
      Brain Injury: Expectations Based on Orientation Log Classification.
AB  - Objective: This study examined performance on the Medical Symptom Validity test
      (MSVT) during acute rehabilitation for moderate-severe traumatic brain injury
      (TBI) stratified by Orientation Log (O-Log) scores. Method: Participants were 77
      prospectively enrolled persons who sustained moderate-severe TBI and were acutely
      hospitalized secondary to the cognitive, medical and physical sequelae of their
      TBI. Participants were administered neuropsychological metrics, the O-Log and the
      MSVT a mean of 44 days post injury. Results: Significantly lower neurocognitive
      test scores were observed among participants who remained in post-traumatic
      amnesia (O-Log scores ranging from 20 to 24) versus those who were oriented (O
      Log scores ranging from 25 to 30). MSVT performance was lower among participants
      who remained in post-traumatic amnesia. When participants O-Log scores were
      unimpaired (30), performance on the MSVT was also unimpaired on immediate
      recognition (IR) and delayed recognition (DR). A small percentage of participants
      performed below MSVT interpretive expectations on CNS. As O-Log scores decreased,
      MSVT performance also declined on some, but not all MSVT metrics. The sample as a
      whole performed at or above expectations on MSVT criterion B2 (IR) = 96.6%; (DR)
      = 94.8%; consistency (CNS) = 92.9%; paired associate (PA) = 86.4% and delayed
      free recall (FR) = 46.8%. Conclusions: MSVT performance stratified by O-Log
      scores provides basal expectation levels for persons with acute, moderate-severe
      impairment in cognitive skills secondary to TBI. Our data demonstrate that
      persons with significant neurocognitive impairment who are oriented generally
      perform at or above MSVT interpretive guidelines.

PMID- 28431036
TI  - Effects of Delay Duration on the WMS Logical Memory Performance of Older Adults
      with Probable Alzheimer's Disease, Probable Vascular Dementia, and Normal
      Cognition.
AB  - Objective: To examine how the duration of time delay between Wechsler Memory
      Scale (WMS) Logical Memory I and Logical Memory II (LM) affected participants'
      recall performance. Method: There are 46,146 total Logical Memory administrations
      to participants diagnosed with either Alzheimer's disease (AD), vascular dementia
      (VaD), or normal cognition in the National Alzheimer's Disease Coordinating
      Center's Uniform Data Set. Results: Only 50% of the sample was administered the
      standard 20-35 min of delay as specified by WMS-R and WMS-III. We found a
      significant effect of delay time duration on proportion of information retained
      for the VaD group compared to its control group, which remained after adding LMI
      raw score as a covariate. There was poorer retention of information with longer
      delay for this group. This association was not as strong for the AD and
      cognitively normal groups. A 24.5-min delay was most optimal for differentiating
      AD from VaD participants (47.7% classification accuracy), an 18.5-min delay was
      most optimal for differentiating AD versus normal participants (51.7%
      classification accuracy), and a 22.5-min delay was most optimal for
      differentiating VaD versus normal participants (52.9% classification accuracy).
      Conclusions: Considering diagnostic implications, our findings suggest that test
      administration should incorporate precise tracking of delay periods. We recommend
      a 20-min delay with 18-25-min range. Poor classification accuracy based on LM
      data alone is a reminder that story memory performance is only one piece of data
      that contributes to complex clinical decisions. However, strict adherence to the
      recommended range yields optimal data for diagnostic decisions.

PMID- 28431038
TI  - Dietary exposure to emulsifiers and detergents and the prevalence of
      cardiovascular disease.

PMID- 28431037
TI  - Gestational Diabetes Alters Functions in Offspring's Umbilical Cord Cells With
      Implications for Cardiovascular Health.
AB  - Because noncommunicable diseases such as type 2 diabetes mellitus have their
      roots in prenatal development and conditions such as maternal gestational
      diabetes mellitus (GDM), we aimed to test this hypothesis in primary cells
      derived from the offspring of mothers with GDM compared with control subjects. We
      have assessed primary umbilical cord-derived cells such as human umbilical vein
      endothelial cells (HUVECs) and Wharton's jelly-derived mesenchymal stem cells
      from the offspring of mothers with and without GDM. We have compared the primary
      isolates in cell-based assays measuring proliferation, mitochondrial oxygen
      consumption, and the ability to support blood vessel growth. We conducted gene
      expression microarray studies with subsequent pathway analysis and candidate gene
      validation. We observed striking differences between the two groups, such as
      lower metabolic rates and impairment of endothelial tube formation in cells with
      GDM background. HUVECs from subjects with maternal GDM have lower expression of
      the antiapoptotic protein BCL-xL, suggesting compromised angiogenic capabilities.
      Comparative gene expression analysis revealed blood vessel formation as a major
      pathway enriched in the GDM-derived HUVECs with the surface marker CD44 as a gene
      underexpressed in the GDM group. Functional validation of CD44 revealed that it
      regulates tube formation in HUVECs, thereby providing insights into a pathway
      imprinted in primary umbilical cord-derived cells from GDM offspring. Our data
      demonstrate that primary cells isolated from the umbilical cord of offspring born
      to mothers with GDM maintain metabolic and molecular imprints of maternal
      hyperglycemia, reflecting an increased risk for cardiovascular disease later in
      life.

PMID- 28431039
TI  - Genomic data for 78 chickens from 14 populations.
AB  - Background: Since the domestication of the red jungle fowls ( Gallus gallus ;
      dating back to ~10 000 B.P.) in Asia, domestic chickens ( Gallus gallus
      domesticus ) have been subjected to the combined effects of natural selection and
      human-driven artificial selection; this has resulted in marked phenotypic
      diversity in a number of traits, including behavior, body composition, egg
      production, and skin color. Population genomic variations through diversifying
      selection have not been fully investigated. The whole genomes of 78 domestic
      chickens were sequenced to an average of 18-fold coverage for each bird. By
      combining this data with publicly available genomes of five wild red jungle fowls
      and eight Xishuangbanna game fowls, we conducted a comprehensive comparative
      genomics analysis of 91 chickens from 17 populations. After aligning ~21.30
      gigabases (Gb) of high-quality data from each individual to the reference chicken
      genome, we identified ~6.44 million (M) single nucleotide polymorphisms (SNPs)
      for each population. These SNPs included 1.10 M novel SNPs in 17 populations that
      were absent in the current chicken dbSNP (Build 145) entries. The current data is
      important for population genetics and further studies in chickens and will serve
      as a valuable resource for investigating diversifying selection and candidate
      genes for selective breeding in chickens.

PMID- 28431040
TI  - Prospective Assessment of Pain and Comfort in Chronic Pain Patients Undergoing
      Interventional Pain Management Procedures.
AB  - Objective: Interventional pain management procedures have an important role in
      the management of chronic pain. The present study seeks to identify the
      proportion of patients who experience severe pain during pain procedures either
      with or without sedation. There is then an attempt to identify any association of
      high pain levels with factors such as age, gender, ethnicity, preprocedure pain
      level, procedure type, tobacco use, and baseline pharmaceuticals taken for both
      pain and/or mood disorder management. Methods: This is a prospective survey study
      evaluating patients' discomfort during interventional pain procedures in an
      outpatient academic facility. Patient discomfort was assessed by the PROcedural
      Sedation Assessment Survey (PROSAS) and modified for nonsedation cases. Results:
      There were 155 patients in the survey, with 20 of these receiving nonspinal
      injections. Of the remaining 135 patients who underwent spinal injections, only
      10 received conscious sedation. On average, 14.2% experienced severe pain during
      spinal injections, whereas 20% experienced severe pain with nonspinal injections.
      Though few patients received conscious sedation, most of these (60%) experienced
      high levels of pain. There was no correlation between level of procedural pain
      with age, gender, ethnicity, preprocedure pain level, procedure type, tobacco
      use, or medication type used. Conclusions: The majority of patients who undergo
      nonsedated interventional pain management procedures do not experience severe
      pain. There is a small but appreciable group of subjects who seem to experience
      severe pain that cannot be correlated to any particular clinical characteristic
      in a standard patient evaluation. Even with standard conscious sedation, there is
      no clear best method to ensure patient comfort for this high-pain level group.

PMID- 28431041
TI  - Bidirectional approaches for optogenetic regulation of gene expression in
      mammalian cells using Arabidopsis cryptochrome 2.
AB  - Optogenetic tools allow regulation of cellular processes with light, which can be
      delivered with spatiotemporal resolution. In previous work, we used cryptochrome
      2 (CRY2) and CIB1, Arabidopsis proteins that interact upon light illumination, to
      regulate transcription with light in yeast. While adopting this approach to
      regulate transcription in mammalian cells, we observed light-dependent
      redistribution and clearing of CRY2-tethered proteins within the nucleus. The
      nuclear clearing phenotype was dependent on the presence of a dimerization domain
      contained within the CRY2-fused transcriptional activators. We used this
      knowledge to develop two different approaches to regulate cellular protein levels
      with light: a system using CRY2 and CIB1 to induce protein expression with light
      through stimulation of transcription, and a system using CRY2 and a LOV-fused
      degron to simultaneously block transcription and deplete protein levels with
      light. These tools will allow precise, bi-directional control of gene expression
      in a variety of cells and model systems.

PMID- 28431042
TI  - Cis-Regulatory Divergence in Gene Expression between Two Thermally Divergent
      Yeast Species.
AB  - Gene regulation is a ubiquitous mechanism by which organisms respond to their
      environment. While organisms are often found to be adapted to the environments
      they experience, the role of gene regulation in environmental adaptation is not
      often known. In this study, we examine divergence in cis-regulatory effects
      between two Saccharomycesspecies, S. cerevisiaeand S. uvarum, that have
      substantially diverged in their thermal growth profile. We measured allele
      specific expression (ASE) in the species' hybrid at three temperatures, the
      highest of which is lethal to S. uvarumbut not the hybrid or S. cerevisiae. We
      find that S. uvarumalleles can be expressed at the same level as S.
      cerevisiaealleles at high temperature and most cis-acting differences in gene
      expression are not dependent on temperature. While a small set of 136 genes show
      temperature-dependent ASE, we find no indication that signatures of directional
      cis-regulatory evolution are associated with temperature. Within promoter regions
      we find binding sites enriched upstream of temperature responsive genes, but only
      weak correlations between binding site and expression divergence. Our results
      indicate that temperature divergence between S. cerevisiaeand S. uvarumhas not
      caused widespread divergence in cis-regulatory activity, but point to a small
      subset of genes where the species' alleles show differences in magnitude or
      opposite responses to temperature. The difficulty of explaining divergence in cis
      regulatory sequences with models of transcription factor binding sites and
      nucleosome positioning highlights the importance of identifying mutations that
      underlie cis-regulatory divergence between species.

PMID- 28431043
TI  - Male Gender Associated with Post-Treatment Seizure Risk of Pediatric
      Arteriovenous Malformation Patients.
AB  - BACKGROUND: Seizure risk has not been fully characterized in pediatric patients
      with arteriovenous malformations (AVMs). OBJECTIVE: To describe the progression
      and risk factors of post-treatment seizure in children with AVMs. METHODS: We
      retrospectively reviewed pediatric patients diagnosed with intracranial AVMs at
      our institution between 1990 and 2013. Clinical and angiographic variables were
      included in univariate and multivariate Cox proportional hazard models to explore
      risk factors associated with time-related seizure outcomes. The outcome event is
      defined as first seizure occurrence after initial treatment. Kaplan-Meier
      survival curve is depicted for each significant variable, and survival
      differences were confirmed by Log-rank test. RESULTS: We included 90 pediatric
      patients with complete data in our study cohort. Average age is 13.3 +/- 3.8
      years with 43.3% male patients. Thirty-seven patients had a hemorrhagic
      presentation, and 39 patients presented with seizure. Post-treatment seizure
      occurred in 33 patients (36.7%) over an average follow-up period of 8.1 +/- 10.6
      years; average time to onset is 5.3 +/- 8.2 years, with partial seizures as the
      most common presentation. Multivariate Cox proportional hazard regression
      revealed seizure presentation ( P = .005), male gender ( P = .026), and
      nonconservative treatment modality to be significantly associated with earlier
      onset of post-treatment seizure after adjusting for AVM location and deep venous
      drainage. Overall annualized seizure risk is 7.4% for patients with pretreatment
      seizure, and 1.4% for those without. CONCLUSION: Risk of seizure persists after
      treatment in pediatric AVM patients. Seizure presentation, male gender, and
      nonconservative management are associated with increased risk of post-treatment
      seizure. Early identification of these risk factors provides important
      information for determining seizure management strategies.

PMID- 28431044
TI  - Leonurine attenuates fibroblast-like synoviocyte-mediated synovial inflammation
      and joint destruction in rheumatoid arthritis.
AB  - Objective: To explore the role of leonurine in the regulation of synovial
      inflammation and joint destruction inRA. Methods: Fibroblast-like synoviocytes
      were isolated from synovial tissue from RA patients. Pro-inflammatory cytokine
      and MMP expression was evaluated using real-time PCR and a cytometric bead array.
      Cell migration and invasion in vitro were measured using the Boyden chamber
      method and the scratch assay, respectively. Protein expression was measured by
      western blotting. Nuclear factor kappa B (NF-kappaB) nuclear translocation was
      detected by immunofluorescence. The in vivo effect of leonurine was evaluated in
      mice with CIA. Results: Leonurine treatment significantly decreased the
      production of pro-inflammatory cytokines (IL-1beta, IL-6, IL-8 and TNFalpha) and
      MMPs (MMP-1 and MMP-3) and suppressed the migration and invasion of RA fibroblast
      like synoviocytes. The molecular analysis revealed that leonurine impaired
      TNFalpha-induced NF-kappaB signalling by inhibiting the phosphorylation and
      degradation of inhibitor of NF-kappaB alpha (IkappaBalpha) and subsequently
      preventing the nuclear translocation of the NF-kappaB p65 subunit. Leonurine also
      inhibited the p38 and Jun N-terminal kinase mitogen-activated protein kinases
      signalling pathways without affecting ERK signalling. Intraperitoneal injection
      of leonurine reduced synovial inflammation, joint destruction and the serum IL
      1beta, IL-6 and TNFalpha levels in mice with CIA. Conclusion: Our findings show
      that leonurine reduces synovial inflammation and joint destruction in RA through
      the NF-kappaB and mitogen-activated protein kinases pathways. Leonurine has
      potential as a therapeutic agent for RA.

PMID- 28431045
TI  - Water table drawdown shapes the depth-dependent variations in prokaryotic
      diversity and structure in Zoige peatlands.
AB  - Microbial communities are important to ecosystem function and sensitive to
      hydrological dynamics. However, we lack predictable knowledge about how soil
      microorganisms respond to water table drawdown in different depths. This research
      used a high-throughput sequencing method to determine the responses of
      prokaryotic communities to the changes of water table and depth on Zoige
      peatlands. Our results showed that water table drawdown reduced alpha diversity
      indices (observed species, Shannon diversity and Chao1 richness) of prokaryotic
      communities. Intriguingly, the reduction of diversity varied in different depths,
      and was statistically significant in intermediate layers (20-30 cm and 50-60 cm),
      but not in the surface (0-10 cm) or deep layer (90-100 cm). In deeper layers
      there was greater relative abundance of most anaerobic microorganisms (e.g.
      Chloroflexi, Planctomyctes and NC10), but lesser amounts of most aerobes (e.g.
      Proteobacteria and Acidobacteria). However, the vertical distribution of
      prokaryotic microbiota along the depth gradient was altered by water table
      drawdown, mainly by enriching oligotrophs (e.g. Acidobcteria) over copiotrophs
      (e.g. Bacteriodetes). In addition, we found that the most important soil
      parameters influencing community structure were soil pH, total organic carbon and
      total nitrogen. Our study illuminates that the variations of prokaryotic
      communities caused by water table drawdown are depth-dependent, and that water
      table drawdown leads to predictive changes of microbiota in peatlands.

PMID- 28431047
TI  - Impact of the SYNTAX scores I and II in patients with diabetes and multivessel
      coronary disease: a pooled analysis of patient level data from the SYNTAX,
      PRECOMBAT, and BEST trials.
AB  - Aims: To assess the impact of the SYNTAX scores I and II in outcomes after
      percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG)
      for patients with diabetes and multivessel disease (MVD). Methods and results: We
      performed a patient-level pooled analysis of three large randomized trials of
      patients with MVD. The impact of coronary anatomic complexity as measured by the
      SYNTAX score in the differences in outcomes following PCI and CABG was assessed
      at a median follow-up of 5 years. We also assessed the performance of the SYNTAX
      II score model in patients with and without diabetes. From the 3280 patients
      enrolled in the three trials, a total of 1068 (32.6%) had diabetes. The rate of
      the composite of death, myocardial infarction (MI), or stroke was similar in the
      PCI and CABG arms in patients with low-intermediate (<=32) SYNTAX scores (15.1%
      vs. 14.9%, respectively; P = 0.93) while it was significantly higher in the PCI
      arm in patients with high (>=33) SYNTAX scores (24.5% vs. 13.2%, respectively; P
      = 0.018). The SYNTAX score II showed good calibration and moderate discrimination
      ability in patients with diabetes (c-index = 0.68) as well as in those without (c
      index = 0.67). Conclusions: Differences in 5 years outcomes following PCI and
      CABG for patients with MVD and diabetes were influenced by anatomic complexity as
      measured by the SYNTAX score. The SYNTAX score II mortality prediction model
      showed similar performance regardless of the diabetes status.

PMID- 28431046
TI  - BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote
      differentiation.
AB  - Mutations in SOX10 cause neurocristopathies which display varying degrees of
      hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as
      a modifier gene that exacerbates the phenotypic severity of Sox10 haplo
      insufficient mice. Conditional deletion of Smarca4 in SOX10 expressing cells
      resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define
      the requirement for the Smarca4 -encoded BRG1 subunit of the SWI/SNF chromatin
      remodeling complex, we employed in vitro models of melanocyte differentiation in
      which induction of melanocyte-specific gene expression is closely linked to
      chromatin alterations. We found that BRG1 was required for expression of Dct,
      Tyrp1 and Tyr, genes that are regulated by SOX10 and MITF and for chromatin
      remodeling at distal and proximal regulatory sites. SOX10 was found to physically
      interact with BRG1 in differentiating melanocytes and binding of SOX10 to the
      Tyrp1 distal enhancer temporally coincided with recruitment of BRG1. Our data
      show that SOX10 cooperates with MITF to facilitate BRG1 binding to distal
      enhancers of melanocyte-specific genes. Thus, BRG1 is a SOX10 co-activator,
      required to establish the melanocyte lineage and promote expression of genes
      important for melanocyte function.

PMID- 28431048
TI  - Letter: Extensive Migration of Young Neurons Into the Infant Human Frontal Lobe.

PMID- 28431049
TI  - Nest use and patterns of egg laying and damage by 4 strains of laying hens in an
      aviary system.
AB  - Laying hens are strongly motivated to use nests for egg laying, and alternative
      production systems (e.g., aviaries) provide artificial sites to meet this need
      and ensure efficient collection of clean, undamaged eggs. However, nests are
      typically not provided to allow simultaneous use by all hens; therefore,
      competition or mislaid eggs can result. To understand the influence of strain on
      laying eggs outside nests and damage to eggs, we compared daily patterns of nests
      use and egg laying among 4 laying hen strains (Hy-Line Brown (HB), Bovans Brown
      (BB), DeKalb White (DW), and Hy-Line W36 (W36)). Hens were observed over 3
      consecutive days in aviaries with colony nests in the enclosure's top tier (2
      nests/unit, 4 aviary units/strain, 144 hens/unit). The number and location of
      hens in nests and the number, location and condition of eggs throughout aviaries
      were recorded. Most eggs (90 to 95%) were laid in nests; however, brown hens
      consistently laid more non-nest eggs and damaged more eggs than white hens (P <=
      0.05). Higher nest occupancy by brown hens was correlated with more non-nest and
      damaged eggs (P <= 0.05). In the morning, brown hens occupied more nest space and
      laid more nest eggs than white hens (e.g., HB vs. DW: 82.97 and 34.66% of space;
      91.35 and 68.73% of nest eggs; P <= 0.05). At midday, white hens occupied more
      nest space and laid more nest eggs than brown hens (e.g., HB vs. DW: 28.47 and
      15.81% of space; 27.39 and 8.29% of nest eggs; P <= 0.05). Brown hens preferred
      right nest compartments and laid more eggs there, whereas white hens preferred
      left compartments and W36 laid more eggs there (P <= 0.05). These findings
      indicate that different strains of hens have different patterns of nest use and
      laying behavior. In brown hens, heavy morning nest use was related to laying eggs
      outside nests and more damaged eggs, suggesting insufficient space for
      oviposition in nests. Specific facility design should be matched to hens'
      preferences to accommodate behavioral needs of different strains.

PMID- 28431050
TI  - Role of adenosine-guided pulmonary vein isolation in patients undergoing catheter
      ablation for atrial fibrillation: a meta-analysis.
AB  - Aims: Adenosine had been reported to unmask dormant conduction and thus identify
      pulmonary vein at risk of reconnection. However, the role of adjunctive adenosine
      infusion after pulmonary vein isolation (PVI) on long-term arrhythmia-free
      survival was still contentious. The purpose of the present meta-analysis was to
      assess the association of adenosine testing with long-term ablation success in
      patients with atrial fibrillation (AF) (i.e. freedom from AF recurrence). Methods
      and Results: We systematically searched the electronic databases and finally
      included 10 studies, with 1771 patients undergoing adenosine-guided PVI and 1787
      patients undergoing conventional PVI. In comparison to conventional PVI alone,
      adenosine-guided PVI improved the arrhythmia-free survival by 17% during a median
      follow-up of 12 months [relative risk (RR): 1.17; 95% confidence interval (CI):
      1.07 to 1.27; P = 0.014]. Patients undergoing adenosine-guided PVI had similar
      fluoroscopy time to those who undergoing conventional PVI [weighted mean
      difference (WMD): 1.76; 95% CI: -5.66 to 9.17; P = 0.64], despite longer
      procedure time (WMD: 20.6; 95% CI: 0.70 to 40.50; P = 0.042). Conclusion: From
      the available data of clinical studies, adenosine-guided PVI was associated with
      an increased arrhythmia-free survival when compared with conventional PVI in
      patients undergoing catheter ablation for AF.

PMID- 28431051
TI  - Safety, long-term outcomes and predictors of recurrence after first-line combined
      endoepicardial ventricular tachycardia substrate ablation in arrhythmogenic
      cardiomyopathy. Impact of arrhythmic substrate distribution pattern. A
      prospective multicentre study.
AB  - Background: First-line endoepicardial ventricular tachycardia (VT) ablation has
      been proposed for patients with arrhythmogenic cardiomyopathy (AC). This study
      reports procedural safety, outcomes, and predictors of recurrence. Methods and
      Results: Forty-one consecutive patients [12 with left ventricle (LV) involvement,
      7 left-dominant] underwent first-line endoepicardial VT substrate ablation.
      Standard bipolar and unipolar thresholds were used to define low-voltage areas
      (LVA). Arrhythmogenic substrate area (ASA) was defined as the area containing
      electrograms with delayed components. Implantable cardioverter defibrillator
      interrogations were evaluated for VT recurrence. Epicardial LVA was larger in all
      cases (102.5 +/- 78.6 vs. 19.3 +/- 24.4 cm2; P< 0.001). Consistent with an
      epicardium-to-endocardium arrhythmogenic substrate progression pattern,
      epicardial ASA (epi-ASA) was negatively correlated with bipolar endocardial LVA
      (r = -0.368; P= 0.035) and with endocardial bipolar/unipolar-LVA (Bi/Uni-LVA)
      ratio (r= -0.38; P= 0.037). A Bi/Uni-LVA ratio >0.23 predicted an epi-ASA <=10
      cm2 (100% sensitivity, 84% specificity). Patients showing an epi-ASA < 10 cm2
      required less epicardial (8.4 +/- 5.8 vs. 25.3 +/- 16; P= 0.045) and more
      endocardial (16.5 +/- 8.6 vs. 7.5 +/- 8.2; P= 0.047) radiofrequency applications.
      One patient with epi-ASA < 10 cm2 died of cardiac tamponade after epicardial
      puncture. Acute success (no VT inducibility after procedure) was achieved in 36
      patients (90%). After 32.2 +/- 21.8 months, 11 (26.8%) patients had VT
      recurrences. Left-dominant AC was associated with an increased risk of recurrence
      (HR = 3.41 [1.1-11.2], P= 0.044; log-rank P= 0.021). Conclusion: First-line
      endoepicardial VT substrate ablation achieves good long-term results in AC. Left
      dominant AC is associated with an increased risk of recurrence. The Bi/Uni-LVA
      ratio identifies patients with limited epicardial arrhythmogenic substrate in
      whom the indication of epicardial approach should be more cautiously assessed.

PMID- 28431052
TI  - Abrupt disruption of remote monitoring transmission as an indicator of safe
      backup mode.

PMID- 28431053
TI  - Occurrence of simultaneous cathodal-anodal capture with left ventricular
      quadripolar leads for cardiac resynchronization therapy: an electrocardiogram
      evaluation.
AB  - Aims: The occurrence of left ventricular (LV) anodal activation during pacing
      with modern multipolar cardiac resynchronization therapy (CRT) systems has never
      been reported. The aim of our study was to demonstrate, by means of
      electrocardiogram (ECG) analysis, the occurrence of simultaneous cathodal-anodal
      LV capture with quadripolar LV leads. Methods and Results: We studied 10 first
      time recipients of a CRT device equipped with a quadripolar LV lead. During
      follow-up, standard supine 12-lead ECGs were obtained in available cathode-to
      anode LV pacing configurations with a pulse amplitude equal to twice the pacing
      threshold. The occurrence of simultaneous cathodal-anodal LV capture was defined
      as the presence of variations in electrocardiographic ventricular activation
      (EVA) when the distal tip (cathode)-to-device can (anode) pacing configuration
      was compared with the distal tip (cathode)-to-proximal ring (anode)
      configuration. In eight patients, we found differences in EVA when different LV
      sites were paced through the unipolar LV tip and unipolar LV ring configurations.
      In these patients, a difference in EVA was detected in 61.5% (59 of 96) of the
      ECG leads (marked difference in 31.3%, slight difference in 30.2%). Changes in
      EVA between unipolar tip-to-can and bipolar tip-to-ring pacing that were
      suggestive of cathodal-anodal LV capture were found in six patients. In these
      patients, a total of 30 (41.7%) ECG leads showed a difference in EVA (marked
      difference in 20.8%, slight difference in 20.8%). Conclusion: In our experience,
      additional anodal capture by the proximal LV ring during LV pacing is provable in
      most recipients of a resynchronization device equipped with a multipolar LV lead.

PMID- 28431054
TI  - The variability of automated QRS duration measurement.
AB  - Aims: Previous studies have demonstrated substantial variability in manual
      assessment of QRS complex duration (QRSd). Disagreements in QRSd measurements
      were also found in several automated algorithms tested on digitized
      electrocardiogram (ECG) recordings. The aim of our study was to investigate the
      variability of automated QRSd measurements performed by two commercially
      available electrocardiographs. Methods and Results: Two GE MAC 5000 (GE-1 and GE
      2) electrocardiographs and two Mortara ELI 350 (Mortara-1 and Mortara-2)
      electrocardiographs were used in the study. Participants for the study were
      recruited from patients hospitalized in the department of cardiology of a
      university hospital. Participants underwent up to four recording sessions within
      a single day with a different electrocardiograph at each session when two to four
      immediately successive ECG recordings were undertaken. In 76 patients, 683 ECGs
      were recorded; the mean QRSd was 109.0 +/- 26.1 ms. The QRSd difference >=10 ms
      between the first and second intra-session ECG was found in 7, 3, 20, and 14% of
      ECG pairs for GE-1, GE-2, Mortara-1, and Mortara-2, respectively. No inter
      session difference in QRSd was found within both manufacturers. In individual
      patients, Mortara calculated the mean QRSd to be longer by 7.3 ms (95% CI: 6.2
      8.5 ms, P < 0.0001) with a 2.1-times (95% CI: 1.9-2.4) greater standard deviation
      of the mean QRSd (7.1 vs. 3.3 ms, P < 0.001). Conclusion: Electrocardiographs
      from two manufacturers measured QRSd values with a systematic difference and a
      significantly different level of precision. This may have important clinical
      implications in selection of suitable candidates for cardiac resynchronization
      therapy.

PMID- 28431055
TI  - Electrocardiographic differentiation of idiopathic right ventricular outflow
      tract ectopy from early arrhythmogenic right ventricular cardiomyopathy.
AB  - Aims: The differentiation between idiopathic right ventricular outflow tract
      (RVOT) arrhythmias and early arrhythmogenic right ventricular cardiomyopathy
      (ARVC) can be challenging. We aimed to assess whether QRS morphological features
      and coupling interval of ventricular ectopic beats (VEBs) can improve
      differentiation between the two conditions. Methods and Results: Twenty
      desmosomal-gene mutation carriers (13 females, mean age 43 years) with no or mild
      ARVC phenotypic expression and 33 age- and sex-matched subjects with idiopathic
      RVOT arrhythmias were studied. All patients exhibited isolated monomorphic VEBs
      with left bundle branch block/inferior axis morphology. The predictive value of
      ectopic QRS morphology and coupling interval was evaluated. Five ectopic QRS
      features were significantly more common in desmosomal-gene mutation carriers than
      in idiopathic RVOT-ventricular arrhythmia patients: maximal QRS duration >160 ms
      (60 vs. 27%, P = 0.02), intrinsicoid deflection time >80 ms (65 vs. 24%, P =
      0.01), initial QRS slurring (40 vs. 12%, P = 0.04), QS pattern in lead V1 (90 vs.
      36%, P < 0.001), and QRS axis >90 degrees  in limb leads (60 vs. 24%, P = 0.01).
      In the multivariate analysis, intrinsicoid deflection time >80 ms [odds ratio
      (OR) = 9.9], QS pattern in lead V1 (OR = 28), and QRS axis >90 degrees  (OR =
      5.7) remained independent predictors of early ARVC. The coupling interval did not
      differ between the two groups. Conclusions: In patients with RVOT VEBs and no
      major electrocardiographic or echocardiographic abnormalities, the ectopic QRS
      morphology aids in the differential diagnosis between idiopathic RVOT arrhythmias
      and early ARVC.

PMID- 28431056
TI  - Long-term outcome of transvenous pacemaker implantation in infants: a
      retrospective cohort study.
AB  - Aim: Evaluation of long-term outcome of transvenous pacemaker (PM) implantation
      in infants. Methods and Results: A retrospective analysis of all transvenous PM
      implantations in infants <10 kg between September 1997 and October 2001 was made.
      Indications for PM implantation, age at implantation, and determinants of long
      term outcome including cardiac function, PM function, and PM (system)
      complications were noted. Seven patients underwent transvenous VVI(R) PM
      implantation. Median age at implantation was 3 days (range: 1 day to 14 months),
      median weight 3.5 kg (range: 2.3-8.7 kg), and median follow-up 14 years (range:
      12.3-16.3 years). Pacemaker indications were congenital complete atrioventricular
      block (n = 4), long QT syndrome with heart block (n = 2), and post-operative
      complete atrioventricular block with sinus node dysfunction (n = 1). No
      procedural complications were noted. Today all patients are alive and symptom
      free with good PM and cardiac function. Two patients underwent PM generator
      relocation for imminent skin necrosis and skin traction. Two patients suffered
      from asymptomatic left subclavian vein occlusion and developed thrombosis on the
      PM electrode. Three patients were converted to an epicardial PM system, due to
      atrial perforation after upgrading procedure (n = 1), syncope with need for
      implantable cardioverter defibrillator implantation (n = 1), and systolic
      dysfunction with development of dilated cardiomyopathy, which normalized under
      cardiac resynchronization therapy pacing (n = 1). Two patients needed
      atrioventricular (AV) valve repair for severe insufficiency. Two patients
      underwent repositioning of dysfunctional PM leads. In five patients, transvenous
      leads were removed. Indications were elective lead replacement (n = 1), atrial
      perforation (n = 1), and switch to an epicardial system (n = 3). Conclusion:
      Transvenous PM implantation in infants (<10 kg) is associated with a high
      incidence of vascular occlusion, thrombosis, and severe atrioventricular valve
      regurgitation during long-term follow-up. We advocate an epicardial approach for
      PM implantation in small children.

PMID- 28431057
TI  - Quantitative analysis of PKP2 and neighbouring genes in a patient with
      arrhythmogenic right ventricular cardiomyopathy caused by heterozygous PKP2
      deletion.
AB  - Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease mainly
      caused by desmosome gene mutations. The genetic culprit, however, remains elusive
      in ~50% of ARVC patients. One of the reasons for missing genetic abnormalities is
      the difficulty in detecting large deletions/duplications, which are called as
      copy number variation (CNV) by the Sanger sequencing method. This study aimed to
      identify CNVs in PKP2 and a part of other desmosome genes in ARVC patients.
      Methods and Results: The study cohort consisted of 71 ARVC probands who were
      diagnosed as definite or borderline cases based on 2010 Task Force Criteria.
      Among them, 32 (45%) carried at least one mutation in desmosome genes detected by
      the Sanger method. Using the multiplex ligation-dependent probe amplification
      method, we identified a male proband (1.4%) with a complete deletion of all PKP2
      coding exons. He was 31 years old and showed exercise-induced sustained
      ventricular tachycardia with superior axis and left bundle-branch block pattern.
      His cardiac magnetic resonance imaging and computed tomography showed right
      ventricular dilatation and reduced ejection fraction. His 12-lead
      electrocardiogram showed T-wave inversion in V1-V3, and late potentials were
      positive, indicating definite ARVC. To confirm the precise location of the
      deletion, we performed relative quantitative PCR. We found complete deletion of
      both SYT10 and ALG10 located in 3' of PKP2; the total deletion size was at least
      1.23 Mb. Conclusion: Screening for CNVs in desmosome genes is useful to identify
      the genetic basis of disease in clinically suspected ARVC patients.

PMID- 28431058
TI  - Additional electrodes on the QuartetTM LV lead provide more programmable pacing
      options than bipolar and tripolar equivalents.
AB  - Aims: The aim of this study was to evaluate any benefits to the number of viable
      pacing vectors and maximal spatial coverage with quadripolar left ventricular
      (LV) leads when compared with tripolar and bipolar equivalents in patients
      receiving cardiac resynchronization therapy (CRT). Methods and Results: A meta
      analysis of five previously published clinical trials involving the QuartetTM LV
      lead (St Jude Medical, St Paul, MN, USA) was performed to evaluate the number of
      viable pacing vectors defined as capture thresholds <=2.5 V and no phrenic nerve
      stimulation and maximal spatial coverage of viable vectors in CRT patients at pre
      discharge (n = 370) and first follow-up (n = 355). Bipolar and tripolar lead
      configurations were modelled by systematic elimination of two and one
      electrode(s), respectively, from the Quartet lead. The Quartet lead with its four
      pacing electrodes exhibited the greatest number of pacing vectors per patient
      when compared with the best bipolar and the best tripolar modelled equivalents.
      Similarly, the Quartet lead provided the highest spatial coverage in terms of the
      distance between two furthest viable pacing cathodes when compared with the best
      bipolar and the best tripolar configurations (P < 0.05). Among the three modelled
      bipolar configurations, the lead configuration with the two most distal
      electrodes resulted in the highest number of viable pacing vectors. Among the
      four modelled tripolar configurations, elimination of the second proximal
      electrode (M3) resulted in the highest number of viable pacing options per
      patient. There were no significant differences observed between pre-discharge and
      first follow-up analyses. Conclusion: The Quartet lead with its four electrodes
      and the capability to pace from four anatomical locations provided the highest
      number of viable pacing vectors at pre-discharge and first follow-up visits,
      providing more flexibility in device programming and enabling continuation of CRT
      in more patients when compared with bipolar and tripolar equivalents.

PMID- 28431059
TI  - Cardiac structural and functional profile of patients with delayed QRS transition
      zone and sudden cardiac death.
AB  - Aims: Delayed QRS transition zone in the precordial leads of the 12-lead
      electrocardiogram (ECG) has been recently associated with increased risk of
      sudden cardiac death (SCD), but the underlying mechanisms are unknown. We
      correlated echocardiographic findings with ECG and clinical characteristics to
      investigate how alterations in cardiac structure and function contribute to this
      risk marker. Methods and Results: From the ongoing population-based Oregon Sudden
      Unexpected Death Study (catchment population ~1 million), SCD cases with prior
      ECG available (n = 627) were compared with controls (n = 801). Subjects with
      delayed transition at V5 or later were identified, and clinical and
      echocardiographic patterns associated with delayed transition were analysed.
      Delayed transition was present in 31% of the SCD cases and 17% of the controls.
      These subjects were older and more likely to have cardiovascular risk factors and
      history of myocardial infarction. Delayed transition was associated with
      increased left ventricular (LV) mass (122.7 +/- 40.2 vs. 102.9 +/- 33.7 g/m2; P <
      0.001), larger LV diameter (53.3 +/- 10.4 vs. 49.2 +/- 8.0 mm; P < 0.001), and
      lower LV ejection fraction (LVEF) (46.4 +/- 15.7 vs. 55.6 +/- 12.5%; P < 0.001).
      In multivariate analysis, delayed transition was independently associated with
      myocardial infarction, reduced LVEF, and LV hypertrophy. The association between
      delayed transition and SCD was independent of the LVEF (OR 1.57; 95% CI 1.04
      2.38; P = 0.032). Conclusion: The underpinnings of delayed QRS transition zone
      extend beyond previous myocardial infarction and reduced LVEF. Since the
      association with sudden death is independent of these factors, this novel marker
      of myocardial electrical remodelling should be explored as a potential risk
      predictor of SCD.

PMID- 28431060
TI  - Catheter ablation vs. antiarrhythmic drug therapy in patients with symptomatic
      atrioventricular nodal re-entrant tachycardia: a randomized, controlled trial.
AB  - Aims: To conduct a randomized trial in order to guide the optimum therapy of
      symptomatic atrioventricular nodal re-entrant tachycardia (AVNRT). Methods and
      Results: Patients with at least one symptomatic episode of tachycardia per month
      and an electrophysiologic diagnosis of AVNRT were randomly assigned to catheter
      ablation or chronic antiarrhythmic drug (AAD) therapy with bisoprolol (5 mg od)
      and/or diltiazem (120-300 mg od). All patients were properly educated to treat
      subsequent tachycardia episodes with autonomic manoeuvres or a 'pill in the
      pocket' approach. The primary endpoint of the study was hospital admission for
      persistent tachycardia cardioversion, during a follow-up period of 5 years. Sixty
      one patients were included in the study. In the ablation group, 1 patient was
      lost to follow-up, and 29 were free of arrhythmia or conduction disturbances at a
      5-year follow-up. In the AAD group, three patients were lost to follow-up. Of the
      remainder, 10 patients (35.7%) continued with initial therapy, 11 patients
      (39.2%) remained on diltiazem alone, and 7 patients (25%) interrupted their
      therapy within the first 3 months following randomization, and subsequently
      developed an episode requiring cardioversion. During a follow-up of 5 years, 21
      patients in the AAD group required hospital admission for cardioversion. Survival
      free from the study endpoint was significantly higher in the ablation group
      compared with the AAD group (log-rank test, P < 0.001). Conclusions: Catheter
      ablation is the therapy of choice for symptomatic AVNRT. Antiarrhythmic drug
      therapy is ineffective and not well tolerated.

PMID- 28431062
TI  - Impact of basal inferolateral scar burden determined by automatic analysis of
      99mTc-MIBI myocardial perfusion SPECT on the long-term prognosis of cardiac
      resynchronization therapy.
AB  - Aims: Left-ventricular (LV) scarring may be associated with a poor response to
      cardiac resynchronization therapy (CRT). The automatic analysis of myocardial
      perfusion single-photon emission computed tomography (MP-SPECT) may provide
      objective quantification of LV scarring. We investigated the impact of LV
      scarring determined by an automatic analysis of MP-SPECT on short-term LV volume
      response as well as long-term outcome. Methods and Results: We studied
      consecutive 51 patients who were eligible to undergo 99mTc-MIBI MP-SPECT both at
      baseline and 6 months after CRT (ischaemic cardiomyopathies 31%). Quantitative
      perfusion SPECT was used to evaluate the defect extent (an index of global
      scarring) and the LV 17-segment regional uptake ratio (an inverse index of
      regional scar burden). The primary outcome was the composite of overall mortality
      or first hospitalization for worsening heart failure. A high global scar burden
      and a low mid/basal inferolateral regional uptake ratio were associated with
      volume non-responders to CRT at 6 months. The basal inferolateral regional uptake
      ratio remained as a predictor of volume non-response after adjusting for the type
      of cardiomyopathy. During a median follow-up of 36.1 months, the outcome occurred
      in 28 patients. The patients with a low basal inferolateral regional uptake ratio
      with a cutoff value of 57% showed poor prognosis (log-rank P= 0.006). Conclusion:
      The scarring determined by automatic analysis of MP-SPECT images may predict a
      poor response to CRT regardless of the pathogenesis of cardiomyopathy. The basal
      inferolateral scar burden in particular may have an adverse impact on long-term
      prognosis.

PMID- 28431061
TI  - High prevalence of arrhythmic and myocardial complications in patients with
      cardiac glycogenosis due to PRKAG2 mutations.
AB  - Aims: Mutations in PRKAG2, the gene encoding for the gamma2 subunit of 5'-AMP
      activated protein kinase (AMPK), are responsible for an autosomal dominant
      glycogenosis with a cardiac presentation, associating hypertrophic cardiomyopathy
      (HCM), ventricular pre-excitation (VPE), and progressive heart block. The aim of
      this study was to perform a retrospective time-to-event study of the clinical
      manifestations associated with PRKAG2 mutations. Methods and Results: A cohort of
      34 patients from 9 families was recruited between 2001 and 2010. DNA were
      sequenced on all exons and flanking sequences of the PRKAG2 gene using Sanger
      sequencing. Overall, four families carried the recurrent p.Arg302Gln mutation,
      and the five others carried private mutations among which three had never been
      reported. In the total cohort, at 40 years of age, the risk of developing HCM was
      61%, VPE 70%, conduction block 22%, and sudden cardiac death (SCD) 20%. The
      global survival at 60 years of age was 66%. Thirty-two per cent of patients (N =
      10) required a device implantation (5 pacemakers and 5 defibrillators) at a
      median age of 66 years, and two patients required heart transplant. Only one
      patient presented with significant skeletal muscle symptoms. No significant
      differences regarding the occurrence of VPE, ablation complications, or death
      incidence were observed between different mutations. Conclusion: This study of
      patients with PRKAG2 mutations provides a more comprehensive view of the natural
      history of this disease and demonstrates a high risk of cardiac complications.
      Early recognition of this disease appears important to allow an appropriate
      management.

PMID- 28431063
TI  - Left ventricular dysfunction is associated with frequent premature ventricular
      complexes and asymptomatic ventricular tachycardia in children.
AB  - Aims: To assess the risk factors for left ventricular (LV) dysfunction in a
      paediatric population with idiopathic frequent premature ventricular contractions
      (PVCs) and asymptomatic ventricular tachycardias (VTs). Methods and Results:
      Paediatric patients with the diagnosis of idiopathic frequent PVCs and
      asymptomatic VTs were retrospectively evaluated. Frequent PVCs were defined as
      >=5% on 24 h Holter recording. Left ventricular dysfunction was defined as a
      shortening fraction of <=28%. Seventy-two children were identified. Six patients
      showed LV dysfunction at diagnosis [age 10 +/- 7 years, 2 (33%) had symptoms such
      as syncope, palpitations, fatigue, and dizziness], and 66 showed normal LV
      function [age 8 +/- 6 years, 22 (33%) with symptoms]. Patients with LV
      dysfunction had a higher percentage of PVCs on Holter recordings (47 +/- 16 vs.
      16 +/- 11%, P = 0.006), higher prevalence of VT [5 (83%) vs. 27 (41%), P = 0.045]
      and sustained ventricular tachycardia (sVT) [3 (50%) vs. 4 (6%), P = 0.001], and
      a higher number of couplets [6 (100%) vs. 34 (52%), P = 0.030]. In patients with
      LV dysfunction, two responded to medication (Classes Ic and II) and five
      underwent ablation, of which one was unsuccessful. During follow-up, LV function
      normalized in five of six patients. In patients with a normal function, none
      developed LV dysfunction during the follow-up. Conclusion: In children with
      idiopathic PVCs and asymptomatic VTs, development of LV dysfunction is associated
      with a higher burden of PVCs, the presence of sVTs, and couplets. Left
      ventricular dysfunction appears to be reversible if the burden of PVCs is
      decreased by medication or ablation.

PMID- 28431064
TI  - Is mortality a useful parameter for public reporting in pacemaker implantation?
      Results of an obligatory external quality control programme.
AB  - Aims: To evaluate if public reporting of pacemaker implantation-associated
      mortality is meaningful in a large contemporary patient cohort. Methods and
      Results: The database of the obligatory external quality control programme in the
      Federal State of Hessen, Germany, of patients undergoing permanent pacemaker
      (PPM) implantation was evaluated retrospectively. We compared the baseline
      features of patients who died compared with those who did not during
      hospitalization after PPM. Of 5079 patients who underwent PPM implantation in
      2009, 74 (1.5%) died during the hospital stay. Cause of death was available in
      70/74 patients (94.6%) who died. Deceased patients were older (79.6 +/- 8.7 vs.
      76.3 +/- 9.9 years, P = 0.006), had worse American Society of Anesthesiologists
      (ASA) physical status (P < 0.001), lower ejection fraction (P < 0.001), a greater
      prevalence of high-degree atrioventricular-block (44.3 vs. 35.0%, P = 0.001), and
      were more likely to receive single-chamber devices (41.4 vs. 25.0%, P < 0.002).
      Perioperative complications were similar in both cohorts. Death was not
      attributable directly to PPM procedure in any patients but was related to (i) non
      device-related infections (28.6%), (ii) heart failure (25.7%), (iii) extracardiac
      diseases (21.4%), (iv) multiorgan failure (8.6%), (v) previous resuscitation with
      hypoxic brain damage (8.6%), and (vi) arrhythmogenic death (7.1%). Conclusion:
      Mortality associated with PPM implantation in vast majority of cases was not
      related to the procedure, but to comorbidities and other existing diseases at the
      time of PPM implantation. Thus, PPM implantation in-hospital mortality should not
      be chosen for public reporting comparing hospital quality, even after adjusting
      for baseline risk.

PMID- 28431065
TI  - CHA2DS2-VASc score and blood biomarkers to identify patients with atrial high
      rate episodes and paroxysmal atrial fibrillation.
AB  - Aims: Paroxysmal atrial fibrillation (PAF) is often asymptomatic but nonetheless
      harmful. We evaluated the performance of disease-related blood biomarkers and
      CHA2DS2-VASc score to discriminate for PAF in patients with continuous rhythm
      monitoring. Methods and Results: Clinical data and blood samples were obtained
      from patients with dual-chamber pacemakers selected according to the absence
      (no_AHRE) or presence of Atrial High-Rate Episodes (AHRE) >6 min in recent device
      history (case-control approach). We included 93 patients (n = 49 AHRE, n = 44
      no_AHRE). In a subgroup with high AHRE burden and confirmed PAF 15 biomarkers
      were evaluated (n = 19 AHRE-AF vs. n = 20 no_AHRE). Significantly regulated
      biomarkers were then tested in all patients to distinguish no_AHRE from AHRE
      (receiver operating characteristics analysis). Hsp27, TGFbeta1, cystatin C,
      matrix metalloproteinases MMP-2,-3,-9, albumin, and serum uric acid were not
      altered in the subgroup. Tissue inhibitors of metalloproteinases (TIMP) -1,-2,-4;
      NT-proANP, NT-proBNP, IL-6 and serum amyloid protein A were significantly
      different in AHRE vs. no_AHRE (subgroup and whole cohort), with best
      discriminatory performance for TIMP-4. Biomarkers performed better than CHADS2
      VASc for AHRE discrimination. Intracardial electrograms and medical history from
      seven AHRE patients suggested atrial tachycardia and not AF (AHRE-AT). Four of
      the most relevant regulated biomarkers (TIMP-4, TIMP-2, SAA, NT-proBNP) behaved
      similarly in AHRE-AT and AHRE-AF. NT-proBNP >150 pg/mL indicated an odds ratio of
      12.9 for AHRE. Combining two biomarkers significantly improved discrimination of
      AHRE. Conclusion: TIMP-4, NT-proANP, NT-proBNP were strongest associated with PAF
      and AHRE. The discriminatory performance of CHADS2-VASc for PAF was increased by
      addition of selected biomarkers.

PMID- 28431066
TI  - Limited left atrial surgical ablation effectively treats atrial fibrillation but
      decreases left atrial function.
AB  - Aims: Limited left atrial (LA) surgical ablation with bipolar radiofrequency is
      considered to be an effective procedure for treatment of atrial fibrillation
      (AF). We studied whether limited LA surgical ablation concomitant to cardiac
      surgery is able to maintain LA function. Methods and Results: Thirty-six
      consecutive patients (age 66 +/- 12 years, 53% male, 78% persistent AF) scheduled
      for valve surgery and/or coronary revascularization and concomitant LA surgical
      ablation were included. Epicardial pulmonary vein isolation (PVI) and additional
      endo-epicardial lines were performed using bipolar radiofrequency. An age- and
      gender-matched control group (n = 36, age 66 +/- 9 years, 69% male, 81%
      paroxysmal AF) was selected from patients undergoing concomitant epicardial PVI
      only. Left atrial dimensions and function were assessed on two-dimensional
      echocardiography preoperatively and at 3- and 12-month follow-up. Sinus rhythm
      (SR) maintenance was 67% for limited LA ablation and 81% for PVI at 1-year follow
      up (P = 0.18). Left atrial volume decreased from 72 +/- 21 to 50 +/- 14 mL (31%,
      P < 0.01) after limited LA ablation and from 65 +/- 23 to 56 +/- 20 mL (14%, P <
      0.01) after PVI. Atrial transport function was restored in 54% of patients in SR
      after limited LA ablation compared with 100% of patients in SR after PVI. Atrial
      strain and contraction parameters (LA ejection fraction, A-wave velocity,
      reservoir function, and strain rate) significantly decreased after limited LA
      ablation. After PVI, strain and contraction parameters remained unchanged.
      Conclusion: Even limited LA ablation decreased LA volume, contraction, transport
      function, and compliance, indicating both reverse remodelling combined with
      significant functional deterioration. In contrast, surgical PVI decreased LA
      volume while function remained unchanged.

PMID- 28431067
TI  - Strategies for prediction and early detection of atrial fibrillation: present and
      future.

PMID- 28431069
TI  - (Tpeak - Tend)/QRS and (Tpeak - Tend)/(QT * QRS): novel markers for predicting
      arrhythmic risk in the Brugada syndrome.

PMID- 28431068
TI  - Self-reported physical activity and major adverse events in patients with atrial
      fibrillation: a report from the EURObservational Research Programme Pilot Survey
      on Atrial Fibrillation (EORP-AF) General Registry.
AB  - Aims: Physical activity is protective against cardiovascular (CV) events, both in
      general population and in high-risk CV cohorts. However, the relationship between
      physical activity with major adverse outcomes in atrial fibrillation (AF) is not
      well-established. Our aim was to analyse this relationship in a 'real-world' AF
      population. Second, we investigated the influence of physical activity on
      arrhythmia progression. Methods and Results: We studied all patients enrolled in
      the EURObservational Research Programme on AF (EORP-AF) Pilot Survey. Physical
      activity was defined as 'none', 'occasional', 'regular', and 'intense', based on
      patient self-reporting. Data on physical activity were available for 2442
      patients: 38.9% reported none, 34.7% occasional, 21.7% regular, and 4.7% intense
      physical activity. Prevalence of the principal CV risk factors progressively
      decreased from none to intense physical activity. Lower rates of CV death, all
      cause death, and composite outcomes were found in AF patients who reported
      regular and intense physical activity (P < 0.0001). Increasing physical activity
      was inversely associated with CV death/any thromboembolic event (TE)/bleeding in
      the whole cohort, irrespective of gender, paroxysmal AF, elderly age, or high
      stroke risk. Any level of physical activity intensity was significantly
      associated with lower risk of CV death/any TE/bleeding at 1-year follow-up.
      Physical activity was not significantly associated with arrhythmia progression.
      Conclusion: Atrial fibrillation patients taking regular exercise were associated
      with a lower risk of all-cause death, even when we considered various subgroups,
      including gender, elderly age, symptomatic status, and stroke risk class. Efforts
      to increase physical activity among AF patients may improve outcomes in these
      patients.

PMID- 28431070
TI  - Emerging molecular therapies targeting myocardial infarction-related arrhythmias.
AB  - Cardiac disease is the leading cause of death in the developed world. Ventricular
      arrhythmias associated with myocardial ischaemia and/or infarction are a major
      contributor to cardiovascular mortality, and require improved prevention and
      treatment. Drugs, devices, and radiofrequency catheter ablation have made
      important inroads, but have significant limitations ranging from incomplete
      success to undesired toxicities and major side effects. These limitations derive
      from the nature of the intervention. Drugs are frequently ineffective, target the
      entire heart, and often do not deal with the specific arrhythmia trigger or
      substrate. Devices can terminate rapid rhythms but at best indirectly affect the
      underlying disease, while ablation, even when appropriately targeted, induces
      additional tissue damage. In contrast, exploration of gene and cell therapies are
      expected to provide a targeted, non-destructive, and potentially regenerative
      approach to ischaemia- and infarction-related arrhythmias. Although these
      approaches are in the early stages of development, they carry substantial
      potential to advance arrhythmia prevention and treatment.

PMID- 28431072
TI  - Time to implement fitness and reduction of fatness in atrial fibrillation
      therapy.

PMID- 28431073
TI  - Dormant pulmonary vein conduction before ablation revealed by adenosine: evidence
      for intermittent venoatrial conduction?

PMID- 28431074
TI  - European Heart Rhythm Association (EHRA) consensus document on the management of
      supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia
      Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de
      Estimulacion Cardiaca y Electrofisiologia (SOLAECE).

PMID- 28431075
TI  - Wilkoff BL, et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on
      optimal implantable cardioverter-defibrillator programming and testing.

PMID- 28431076
TI  - Cryoballoon pulmonary vein isolation and lung lobectomy.

PMID- 28431077
TI  - Implantable cardioverter defibrillator use for primary prevention in ischaemic
      and non-ischaemic heart disease-indications in the post-DANISH trial era: results
      of the European Heart Rhythm Association survey.
AB  - Implantable cardioverter-defibrillator (ICD) is the standard of care for
      prevention of sudden cardiac death (SCD) in high-risk patients. For primary
      prevention of SCD, in patients with ischaemic heart disease, there is more robust
      data on the effect of ICD therapy compared with patients with non-ischaemic heart
      disease, but current real-life practice may differ substantially. The aim of this
      European Heart Rhythm Association survey was to evaluate the clinical practice
      regarding implantation of ICD for primary prevention among European countries in
      patients with non-ischaemic and ischaemic heart disease. Furthermore, we wanted
      to investigate the impact of the results of the recently published DANISH trial
      on clinical practice among European countries. In total, 48 centres from 17
      different countries responded to the questionnaire. The majority did not implant
      ICD for primary prevention on a regular basis in patients with non-ischaemic
      heart disease despite current guidelines. Also, centres have changed their
      indications after the recent report on the efficacy of ICD in these patients. In
      patients with ischaemic heart disease, the guidelines for primary prevention ICD
      were followed on a regular basis, and no relevant change in indications were
      reported.

PMID- 28431078
TI  - Effect of threonine on secretory immune system using a chicken intestinal ex vivo
      model with lipopolysaccharide challenge.
AB  - Secretory IgA (sIgA) and its transcytosis receptor, polymeric immunoglobulin
      receptor (pIgR), along with mucus, form the first lines of intestinal defense.
      Threonine (Thr) is a major component of intestinal mucins and IgA, which are
      highly secreted under lipopolysaccharide (LPS) induced inflammation. In the
      current study, the effect of Thr on the secretory immune system was determined in
      an ex vivo chicken ileal explant model. Results showed that a 2-hour Thr
      deprivation of culture medium induced a compensatory increase in the mRNA
      expression of interleukin-8 (IL-8), mucin 2 (MUC2), and IgA during LPS challenge,
      and this increase was suppressed with Thr addition to the media (P <= 0.05),
      suggesting that Thr was required for mucin and IgA production after exposure to
      LPS. Similarly, a 2-hour culture of explants from birds fed a Thr adequate diet
      showed an increase in the mRNA abundance of IL-8, MUC2, and IgA with LPS
      treatment (P <= 0.003), which had a trend to be attenuated with Thr
      supplementation in the media (P <= 0.10). In contrast, explants from birds fed a
      Thr deficient diet had no response to LPS treatment. These results indicated that
      in vivo Thr deficiency induced impaired inflammatory and secretory immune
      responses in broiler chicks. Furthermore, our results revealed that induction of
      MUC2 and pIgR gene expression required nuclear factor-kappaB (NF-kappaB)
      activation. Additionally, IgA transcytosis may be dependent on extracellular
      regulated protein kinase (ERK) activation, which may indirectly impact pIgR gene
      expression.

PMID- 28431079
TI  - Precision Pain Medicine: Can We Deliver Targeted Pain Therapies for the Oncologic
      Patient in the 21st Century?

PMID- 28431071
TI  - J-Wave syndromes expert consensus conference report: Emerging concepts and gaps
      in knowledge.

PMID- 28431081
TI  - Bilateral adrenal haemorrhage.

PMID- 28431080
TI  - Systematic Review of Measures Used in Pictorial Cigarette Pack Warning
      Experiments.
AB  - Background: We sought to describe characteristics and psychometric properties of
      measures used in pictorial cigarette pack warning experiments and provide
      recommendations for future studies. Methods: Our systematic review identified 68
      pictorial cigarette pack warning experiments conducted between 2000 and 2016 in
      22 countries. Two independent coders coded all studies on study features,
      including sample characteristics, theoretical framework, and constructs assessed.
      We also coded measurement characteristics, including construct, number of items,
      source, reliability, and validity. Results: We identified 278 measures
      representing 61 constructs. The most commonly assessed construct categories were
      warning reactions (62% of studies) and perceived effectiveness (60%). The most
      commonly used outcomes were affective reactions (35%), perceived likelihood of
      harm (22%), intention to quit smoking (22%), perceptions that warnings motivate
      people to quit smoking (18%), and credibility (16%). Only 4 studies assessed
      smoking behavior. More than half (54%) of all measures were single items. For
      multi-item measures, studies reported reliability data 68% of the time (mean
      alpha = 0.88, range alpha = 0.68-0.98). Studies reported sources of measures only
      33% of the time and rarely reported validity data. Of 68 studies, 37 (54%)
      mentioned a theory as informing the study. Conclusions: Our review found great
      variability in constructs and measures used to evaluate the impact of cigarette
      pack pictorial warnings. Many measures were single items with unknown
      psychometric properties. Recommendations for future studies include a greater
      emphasis on theoretical models that inform measurement, use of reliable and
      validated (preferably multi-item) measures, and better reporting of measure
      sources. Implications: Robust and consistent measurement is important for
      building a strong, cumulative evidence base to support pictorial cigarette pack
      warning policies. This systematic review of experimental studies of pictorial
      cigarette warnings demonstrates the need for standardized, theory-based measures.

PMID- 28431082
TI  - Compositional differences among female-associated and embryo-associated
      microbiota of the viviparous Pacific Beetle cockroach, Diploptera punctata.
AB  - All cockroach species, except one, harbor the endosymbiont Blattabacterium,
      transmitted from females to embryos. Adult cockroaches acquire non
      Blattabacterium bacteria as part of their gut microbiota over time, but our
      knowledge of the possible transmission of these non-Blattabacterium bacteria from
      females to embryos is rudimentary. We characterized the gut microbiota of gravid
      viviparous Diploptera punctata females and the non-Blattabacterium microbiota of
      associated developing embryos, as well as the gut microbiota of non-gravid
      females, and the microbiota of orphan embryos (females not included), following
      high-throughput sequencing of the 16S rRNA gene to assess bacterial transference.
      We determined significant differences in community composition between gravid
      females and associated embryos and overall greater similarity in community
      composition among embryos than adult females. Results suggest various routes of
      transference of bacteria from females or the environment to embryos. The
      bacterial families Halomonadaceae and Shewanellaceae were more abundant in
      embryos than in gravid females. The functional relevance of these families
      remains to be elucidated, but provisioning of amino acids deficient in the brood
      sac secretion is a possibility. Overall, our results highlight the need for
      further studies investigating the uptake and selective screening of microbes by
      D. punctata embryos, as well as their functions.

PMID- 28431083
TI  - Repellent Effects of Different Celery Varieties in Bemisia tabaci (Hemiptera:
      Aleyrodidae) Biotype Q.
AB  - Y-tube olfactometer and net cages experiments were used to investigate the
      repellent effects of different celery varieties in biotype Q of sweetpotato
      whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), on cucumber,
      Cucumis sativus L. (Cucurbitaceae). Y-tube olfactometer tests showed that
      whiteflies have strong repellent behavior to different celery varieties.
      Intercropping different celery varieties with cucumbers had significant repellent
      effects and oviposition deterrent effects in whiteflies. Results obtained
      demonstrated that the Western Europe celery varieties, Juventus and Ventura, and
      the Chinese celery variety, Jinnan, had good repellent efficacy against the
      whitefly. D-Limonene, beta-myrcene, and (E)-beta-ocimene might be the main active
      components in celery that affected the selection behavior of B. tabaci. In
      Western Europe celery varieties, D-limonene was the main volatile component for
      the repellent effects in B. tabaci; however, the two Chinese celery varieties
      that showed repellent effects had relatively higher volatilization quantities of
      beta-myrcene than of D-limonene.

PMID- 28431084
TI  - Sonographic barcode sign of pneumothorax.

PMID- 28431085
TI  - Health status in Europe: comparison of 24 urban areas to the corresponding 10
      countries (EURO-URHIS 2).
AB  - Background: : In Europe, over 70% of the population live in urban areas (UAs).
      Most international comparative health research is done using national level data,
      as reliable and comparable urban data are often unavailable or difficult to
      access. This study aims to investigate whether population health is different in
      UAs compared with their corresponding countries. : Routinely available health
      related data were collected by the EURO-URHIS 2 project, for 10 European
      countries and for 24 UAs within those countries. National and UA level data for
      11 health indicators were compared through the calculation of relative
      difference, and geographical patterns within Europe were investigated using the
      Mann Whitney U test. Linear regression modelling was used to adjust for
      population density, gross domestic product and urbanicity. : In general, the
      urban population in Eastern Europe is less healthy than the Western European
      urban population. However, people in Eastern Europe have significantly better
      broad health outcomes in UAs as compared with the corresponding country as a
      whole, whereas people in Western Europe have generally worse broader health
      outcomes in UAs. : For most European countries and UAs that were investigated,
      the national level health status data does not correspond with the health status
      at UA level. In order to identify health problems in UAs and to provide
      information for local health policy, health monitoring and international
      benchmarking should also be conducted at the local level.

PMID- 28431086
TI  - Dynamic Ultrasound Imaging for Quadriceps Tendon Impingement in a Patient with
      Anterior Knee Pain.

PMID- 28431087
TI  - A method for learning a sparse classifier in the presence of missing data for
      high-dimensional biological datasets.
AB  - Motivation: This work addresses two common issues in building classification
      models for biological or medical studies: learning a sparse model, where only a
      subset of a large number of possible predictors is used, and training in the
      presence of missing data. This work focuses on supervised generative binary
      classification models, specifically linear discriminant analysis (LDA). The
      parameters are determined using an expectation maximization algorithm to both
      address missing data and introduce priors to promote sparsity. The proposed
      algorithm, expectation-maximization sparse discriminant analysis (EM-SDA),
      produces a sparse LDA model for datasets with and without missing data. Results:
      EM-SDA is tested via simulations and case studies. In the simulations, EM-SDA is
      compared with nearest shrunken centroids (NSCs) and sparse discriminant analysis
      (SDA) with k-nearest neighbors for imputation for varying mechanism and amount of
      missing data. In three case studies using published biomedical data, the results
      are compared with NSC and SDA models with four different types of imputation, all
      of which are common approaches in the field. EM-SDA is more accurate and sparse
      than competing methods both with and without missing data in most of the
      experiments. Furthermore, the EM-SDA results are mostly consistent between the
      missing and full cases. Biological relevance of the resulting models, as
      quantified via a literature search, is also presented. Availability and
      implementation: A Matlab implementation published under GNU GPL v.3 license is
      available at http://web.mit.edu/braatzgroup/links.html . Contact: braatz@mit.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28431088
TI  - Stationary-phase genes upregulated by polyamines are responsible for the
      formation of Escherichia coli persister cells tolerant to netilmicin.
AB  - Persisters are rare phenotypic variants of regular bacterial cells that survive
      lethal antibiotics or stresses owing to slowing down of their metabolism.
      Recently, we have shown that polyamine putrescine can upregulate persister cell
      formation in Escherichia coli via the stimulation of rpoS expression, encoding a
      master regulator of general stress response. We hypothesized that rmf and yqjD,
      the stationary-phase genes responsible for ribosome inactivation, might be good
      candidates for the similar role owing to their involvement in translational
      arrest and the ability to be affected by polyamines. Using reporter gene fusions
      or single and multiple knockout mutations in rpoS, rmf and yqjD genes, we show in
      this work that (i) E. coli polyamines spermidine and cadaverine can upregulate
      persistence, like putrescine; (ii) polyamine effects on persister cell formation
      are mediated through stimulation of expression of rpoS, rmf and yqjD genes; (iii)
      these genes are involved in persister cell formation sequentially in a dynamic
      fashion as cells enter the stationary phase. The data obtained in this work can
      be used to develop novel tools relying on a suppression of polyamine metabolism
      in bacteria to combat persister cells as an important cause of infections
      refractory to antibiotics.

PMID- 28431090
TI  - Current Status of the Blue Butterfly in Fukushima Research.
AB  - Adverse biological impacts of the Fukushima nuclear accident have been revealed
      using the pale grass blue butterfly, Zizeeria maha, since 2012, which were often
      considered incompatible with the conventional understanding of radiation biology.
      This discrepancy likely originates from different system conditions and
      methodologies. In this article, we first respond to comments from the United
      Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR)
      regarding our study; "technical errors" in unit usage and mathematical models
      noted by UNSCEAR are not errors but reflect our research philosophy not to
      introduce theoretical assumptions associated with unit conversion and
      mathematical fit. Second, we review our recent studies to support the original
      2012 conclusions. Because the high morphological abnormality rate and small body
      size detected in Fukushima in 2011 have already ceased, likely through adaptive
      evolution, their present geographical distributions were investigated throughout
      Japan. Local populations showing relatively high abnormality rates and small body
      sizes were rare and basically restricted to Miyagi and its northern populations
      excluding the Fukushima populations, supporting the causal involvement of the
      accident. Lastly, we stress the importance of understanding the whole picture of
      the biological impacts of the Fukushima accident. In addition to the direct
      radiation impacts, indirect impacts through unknown radiation-associated
      mechanisms, such as immunological responses to insoluble particulate matter and
      nutritional deficiencies in plants and animals, would be in effect. Further
      environmental studies beyond conventional radiation biology and physics are
      necessary to understand the complex responses of organisms, including humans, to
      the Fukushima nuclear accident.

PMID- 28431089
TI  - The Impact of Prescription Drug Monitoring Programs and Prescribing Guidelines on
      Opioid Prescribing Behaviors: A Time for Institutional and Regulatory Changes.

PMID- 28431091
TI  - Suppression of Oral Sweet Taste Sensation with Gymnema sylvestre Affects
      Postprandial Gastrointestinal Blood Flow and Gastric Emptying in Humans.
AB  - An oral sweet taste sensation (OSTS) exaggerates digestive activation
      transiently, but whether it has a role after swallowing a meal is not known.
      Gymnema sylvestre (GS) can inhibit the OSTS in humans. We explored the effect of
      the OSTS of glucose intake on gastrointestinal blood flow, gastric emptying,
      blood-glucose, and plasma-insulin responses during the postprandial phase. Eight
      participants ingested 200 g (50 g * 4 times) of 15% glucose solution containing
      100 mg of 13C-sodium acetate after rinsing with 25 mL of 2.5% roasted green tea
      (control) or 2.5% GS solution. During each protocol, gastrointestinal blood flow
      and gastric emptying were measured by ultrasonography and 13C-sodium acetate
      breath test, respectively. Decreased subjective sweet taste intensity was
      observed in all participants in the GS group. The time to attain a peak value of
      blood flow in the celiac artery and gastric emptying were delayed in the GS group
      compared with the control group. At the initial phase after glucose intake, blood
      glucose and plasma-insulin responses were lower in the GS group than those for
      the control group. These results suggest that the OSTS itself has a substantial
      role in controlling postprandial gastrointestinal activities, which may affect
      subsequent glycemic metabolism.

PMID- 28431092
TI  - Failure of rivaroxaban to prevent thrombosis in four patients with anti
      phospholipid syndrome.

PMID- 28431093
TI  - Interactions Between Cassava Mosaic Geminiviruses and Their Vector, Bemisia
      tabaci (Hemiptera: Aleyrodidae).
AB  - The sweetpotato whitefly, Bemisia tabaci (Gennadius) is the vector of the cassava
      mosaic geminiviruses (CMGs) that cause cassava mosaic disease (CMD). Synergistic
      interactions between B. tabaci and CMGs have been hypothesized as a cause of
      whitefly "super-abundance," which has been a key factor behind the spread of the
      severe CMD pandemic through East and Central Africa. The current study
      investigated this hypothesis by conducting experiments with CMD-susceptible
      cassava varieties infected with different CMGs in both the north-western Lake
      Zone region (pandemic affected) and the eastern Coast Zone where CMD is less
      severe. Male and female pairs of B. tabaci were placed in clip cages for 48 h on
      plants of three cassava varieties at each of the two locations. There were
      significantly more eggs laid on CMG-infected than on CMG-free plants in the Lake
      Zone, whereas in Coast Zone, there were no significant differences. There were no
      significant differences in proportions, mortality, and development duration of
      immature stages of B. tabaci among virus states and cassava variety in the two
      locations. The overall number of eggs was significantly higher with longer
      development duration of the immature stages in the Lake than in the Coast Zone,
      whereas mortality was significantly higher in the Coast than in the Lake Zone.
      Based on these results, it is concluded that there was no net positive
      synergistic interaction between CMGs and B. tabaci for either lowland coastal or
      mid-altitude inland populations. Consequently, other factors seem more likely to
      be the cause of the "super-abundance," and require further investigation.

PMID- 28431094
TI  - Incidence of broiler breast myopathies at 2 different ages and its impact on
      selected raw meat quality parameters.
AB  - White striping (WS) and woody breast (WB) are 2 poultry meat quality defects that
      affect the acceptance of raw breast fillets as well as properties of cooked and
      further processed products. The present study was intended to evaluate the
      incidence of these conditions in broilers at different ages and to compare the
      properties of fillets with different degrees of WS and WB. For this study, 1,920
      birds were processed, at 6 and 9 wk of age, in a standard commercial inline
      processing system. After chilling, carcasses were deboned and butterfly fillets
      were collected and weighed. Individual fillets were scored for normal, moderate,
      severe, and very severe degrees of WS and WB, and for petechial hemorrhagic
      lesions (PHEM, 0 - no lesion to 2 - severe lesion). Representative fillets with
      NORM-WS/WB, SEV-WS, SEV-WB, and SEV-WS/WB were selected and stored at 4 degrees
      C. After 24 h, fillet length, width, cranial height, and caudal height, as well
      as pH, color, and drip loss were recorded. There was an increase in incidence of
      severe and very severe WS and WB conditions at 9 wk compared to 6 wk of age. The
      relationship between fillet weight and the myopathies plateaued at 9 wk of age
      with more fillets showing a higher score. Mean PHEM scores were higher (P < 0.05)
      in SEV-WS, SEV-WB, and SEV-WS/WB compared to NORM-WS/WB birds, both at 6 and 9
      weeks. NORM-WS/WB birds had lower (P < 0.05) live and breast weight, breast
      yield, and cranial and caudal heights, as well as b* value (yellowness) compared
      to SEV-WS/WB. NORM-WS/WB had lower (P < 0.05) pH while NORM-WS/WB and SEV-WS
      samples showed lower (P < 0.05) drip loss when compared to SEV-WB and SEV-WS/WB.
      The results from this study showed that the severe degrees of WS and WB are
      associated with heavier and older birds, and thicker breast fillets. Occurrence
      of severe degrees of WS and/or WB can affect various raw meat quality factors,
      mainly color and water holding capacity.

PMID- 28431095
TI  - Avi-Lution(r) supplemented at 1.0 or 2.0 g/kg in feed improves the growth
      performance of broiler chickens during challenge with bacitracin-resistant
      Clostridium perfringens.
AB  - Avi-Lution(r) is a defined, patented, synbiotic product containing Saccharomyces
      cerevisiae, Enterococcus faecium, and Bacillus spp. Broiler chickens (n = 1,250)
      were experimentally treated as uninoculated controls (uCon), inoculated controls
      (iCon) with Clostridium perfringens, or inoculated and treated with bacitracin
      methylene disalicylate (BMD) at 55 mg/kg as an infected/treated control or Avi
      Lution(r) at 1.0 (AvL1) or 2.0 (AvL2) g/kg in feed for 42 d. Each treatment was
      applied to 10 replicate pens of 25 straight-run, newly hatched chicks. Pens
      treated with AvL1, AvL2, or BMD showed improved growth, feed efficiency, or
      mortality from necrotic enteritis compared with iCon pens at d 14, 28, and 42. No
      differences in these measurements, however, were observed between pens treated
      with AvL1 and AvL2, which suggests that Avi-Lution(r) was effective at 1.0 g/kg
      in feed. Despite improved performance, BMD, AvL1, and AvL2 treatments did not
      decrease the severity of intestinal lesion scores through 42 d of age compared
      with the infected control. These results demonstrate that Avi-Lution(r) improved
      growth performance and feed conversion rates in broilers challenged with
      Clostridium perfringens despite no difference in severity of intestinal lesion
      scores.

PMID- 28431097
TI  - On the appropriate interpretation of evidence: the example of culture media and
      birth weight.

PMID- 28431096
TI  - A new rapid resazurin-based microdilution assay for antimicrobial susceptibility
      testing of Neisseria gonorrhoeae.
AB  - Objectives: Rapid, cost-effective and objective methods for antimicrobial
      susceptibility testing of Neisseria gonorrhoeae would greatly enhance
      surveillance of antimicrobial resistance. Etest, disc diffusion and agar dilution
      methods are subjective, mostly laborious for large-scale testing and take ~24 h.
      We aimed to develop a rapid broth microdilution assay using resazurin (blue),
      which is converted into resorufin (pink fluorescence) in the presence of viable
      bacteria. Methods: The resazurin-based broth microdilution assay was established
      using 132 N. gonorrhoeae strains and the antimicrobials ceftriaxone, cefixime,
      azithromycin, spectinomycin, ciprofloxacin, tetracycline and penicillin. A
      regression model was used to estimate the MICs. Assay results were obtained in
      ~7.5 h. Results: The EC 50 of the dose-response curves correlated well with Etest
      MIC values (Pearson's r  = 0.93). Minor errors resulting from misclassifications
      of intermediate strains were found for 9% of the samples. Major errors
      (susceptible strains misclassified as resistant) occurred for ceftriaxone (4.6%),
      cefixime (3.3%), azithromycin (0.6%) and tetracycline (0.2%). Only one very major
      error was found (a ceftriaxone-resistant strain misclassified as susceptible).
      Overall the sensitivity of the assay was 97.1% (95% CI 95.2-98.4) and the
      specificity 78.5% (95% CI 74.5-82.9). Conclusions: A rapid, objective, high
      throughput, quantitative and cost-effective broth microdilution assay was
      established for gonococci. For use in routine diagnostics without confirmatory
      testing, the specificity might remain suboptimal for ceftriaxone and cefixime.
      However, the assay is an effective low-cost method to evaluate novel
      antimicrobials and for high-throughput screening, and expands the currently
      available methodologies for surveillance of antimicrobial resistance in
      gonococci.

PMID- 28431098
TI  - Egg production and egg quality in free-range laying hens housed at different
      outdoor stocking densities.
AB  - Free-range laying hen systems are increasing in number within Australia.
      Variation in outdoor stocking densities has led to development of a national
      information standard on free-range egg labeling, including setting a maximum
      density of 10,000 hens per hectare. However, there are few data on the impacts of
      differing outdoor densities on production and egg quality. ISA Brown hens in
      small (150 hens) flocks were housed in identical indoor pens, each with access
      (from 21 weeks) to different sized ranges simulating one of three outdoor
      stocking densities (2 replicates each: 2,000 hens/hectare (ha), 10,000 hens/ha,
      20,000 hens/ha). Hen-day production was tracked from 21 through 35 weeks with
      eggs visually graded daily for external deformities. All eggs laid on one day
      were weighed each week. Eggs were collected from each pen at 25, 30, and 36 weeks
      and analyzed for egg quality. There were no effects of outdoor stocking density
      on average hen-day percentage production (P = 0.67), egg weight (P = 0.09),
      percentages of deformed eggs (P = 0.30), shell reflectivity (P = 0.74), shell
      breaking strength (P = 0.07), shell deformation (P = 0.83), or shell thickness (P
      = 0.24). Eggs from hens in the highest density had the highest percentage shell
      weight (P = 0.004) and eggs from the lowest density had the highest yolk color
      score (P < 0.001). The amount of cuticle present did not differ between densities
      (P = 0.95) but some aspects of shell colors (P <= 0.01) and location of
      protoporphyrin IX (P = 0.046) varied. Hen age affected the majority of
      measurements. Stocking density differences may be related to hen diet as previous
      radio-frequency identification tracking of individual hens in these flocks showed
      birds used the range for longer in the lowest density and the least in the
      highest density, including depleting the range of vegetation sooner in the
      smaller ranges. An additional study assessing the relationship between individual
      hen range use, nutrition, and egg quality is warranted.

PMID- 28431100
TI  - Immunoglobulin G4-related disease associated with extensive granulomatous
      changes.

PMID- 28431101
TI  - Mediating Effect of Social Participation on the Relationship between Incontinence
      and Depressive Symptoms in Older Chinese Women.
AB  - Urinary and fecal incontinence affect older women's social participation and
      mental health. This study examined the relationship between incontinence severity
      and depressive symptoms, focusing on the mediating effect of social
      participation, based on secondary analysis of structured interview data collected
      in December 2010 from 467 women age 60 and over in mainland China. Incontinence
      was significantly and positively associated with depressive symptoms but
      negatively associated with social participation. Social participation was
      significantly and negatively associated with depressive symptoms and fully
      mediated the relationship between incontinence and depressive symptoms. These
      findings can inform mental health interventions for incontinent older women,
      including preventing and responding to depressive symptoms by promoting social
      participation.

PMID- 28431102
TI  - An Escherichia coli expression model reveals the species-specific function of
      FtsA from Neisseria gonorrhoeae in cell division.
AB  - Escherichia coli (Ec) has been used to study the function of cell division
      proteins from different microorganisms, especially when genetic tools are limited
      for studying these proteins in their native hosts. The expression of ftsA from
      Neisseria gonorrhoeae (Ng) disrupted cell division in E. coli resulting in a
      significant increase in cell length. In some cells, FtsANg localised to the
      division site and the poles of E. coli cells, but the majority of cells showed no
      specifical localisation. FtsANg did not complement an E. coli ftsA mutant strain.
      Bacterial two-hybrid and GST pull-down assays indicated that FtsANg interacted
      with FtsNEc, but no other cell division proteins from E. coli. This interaction
      was mediated through the 2A and 2B subdomains of FtsANg. This evidence suggests
      that the function of FtsANg is species specific.

PMID- 28431099
TI  - Effect of cold water-induced stress on immune response, pathology and fertility
      in mice during Chlamydia muridarum genital infection.
AB  - Genital infection by Chlamydia trachomatis is the most common bacterial sexually
      transmitted disease worldwide. It causes serious reproductive health
      complications, including pelvic inflammatory disease and infertility. Stress is
      implicated as a risk factor for various infections; however, its effect on
      chlamydia genital infection is unknown. We previously showed that repeated
      exposure of mice to cold water results in increased severity of chlamydia genital
      infection. In this study, cold water-induced stress resulted in (i) elevated
      levels of norepinephrine (NE) and epinephrine in the spleen and genital tract of
      stressed mice; (ii) elevated IL-1beta, TNF-alpha, IL-6 and nitric oxide
      production in macrophage-rich peritoneal cells of mice; (iii) supplement of NE in
      vitro exerts an immunosuppressive effect on splenic T-cell production of
      cytokines; (iv) decreased C. muridarum shedding in the genital tract of
      beta1Adr/beta2Adr receptor KO mice; and (v) a higher rate of infertility in
      infected mice. These results suggest that cold water stress induces the
      production of catecholamines, which may play a critical role in the modulation of
      the immune system leading to increased intensity of C. muridarum genital
      infection.

PMID- 28431103
TI  - Reply to Skowronski and Chambers.

PMID- 28431104
TI  - The potential overlapping populations for treatment with belimumab and rituximab
      using current NHS England and National Institute for Health and Care Excellence
      Guidelines in England and Wales.

PMID- 28431105
TI  - Extinction vs. Rapid Radiation: The Juxtaposed Evolutionary Histories of
      Coelotine Spiders Support the Eocene-Oligocene Orogenesis of the Tibetan Plateau.
AB  - Evolutionary biology has long been concerned with how changing environments
      affect and drive the spatiotemporal development of organisms. Coelotine spiders
      (Agelenidae: Coelotinae) are common species in the temperate and subtropical
      areas of the Northern Hemisphere. Their long evolutionary history and the
      extremely imbalanced distribution of species richness suggest that Eurasian
      environments, especially since the Cenozoic, are the drivers of their
      diversification. We use phylogenetics, molecular dating, ancestral area
      reconstructions, diversity, and ecological niche analyses to investigate the
      spatiotemporal evolution of 286 coelotine species from throughout the region.
      Based on eight genes (6.5 kb) and 2323 de novo DNA sequences, analyses suggest an
      Eocene South China origin for them. Most extant, widespread species belong to the
      southern (SCG) or northern (NCG) clades. The origin of coelotine spiders appears
      to associate with either the Paleocene-Eocene Thermal Maximum or the hot period
      in early Eocene. Tibetan uplifting events influenced the current diversity
      patterns of coelotines. The origin of SCG lies outside of the Tibetan Plateau.
      Uplifting in the southeastern area of the plateau blocked dispersal since the
      Late Eocene. Continuous orogenesis appears to have created localized vicariant
      events, which drove rapid radiation in SCG. North-central Tibet is the likely
      location of origin for NCG and many lineages likely experienced extinction owing
      to uplifting since early Oligocene. Their evolutionary histories correspond with
      recent geological evidence that high-elevation orographical features existed in
      the Tibetan region as early as 40-35 Ma. Our discoveries may be the first
      empirical evidence that links the evolution of organisms to the Eocene-Oligocene
      uplifting of the Tibetan Plateau. [Tibet; biogeography; ecology; molecular clock;
      diversification.].

PMID- 28431106
TI  - Ultrasound cut-off values for intima-media thickness of temporal, facial and
      axillary arteries in giant cell arteritis.
AB  - Objective: To evaluate the intima-media thickness (IMT) of arteries involved in
      GCA for determining cut-off values. Methods: Forty newly diagnosed GCA patients
      in a fast-track GCA clinic and 40 age- and sex-matched controls were included.
      IMT measurement was performed at or within 24 h after diagnosis. The common
      superficial temporal arteries with their frontal and parietal branches and the
      facial arteries were bilaterally examined with a 10-22 MHz probe and the axillary
      artery with a 6-18 MHz probe. Receiver operating characteristics analysis was
      performed for estimating cut-off values. Results: The mean age was 72 years (s.d.
      9) and 68% were females. In the control group, IMT was 0.23 mm (s.d. 0.04), 0.19
      mm (s.d. 0.03), 0.20 mm (s.d. 0.03), 0.24 mm (s.d. 0.05) and 0.59 mm (s.d. 0.10)
      for the common superficial temporal arteries, the frontal and parietal branches,
      the facial arteries and the axillary arteries, respectively. In vasculitic
      segments of GCA patients, IMT was 0.65 mm (s.d. 0.18), 0.54 mm (s.d. 0.18), 0.50
      mm (s.d. 0.17), 0.53 mm (s.d. 0.16) and 1.7 mm (s.d. 0.41), respectively. Cut-off
      values are 0.42, 0.34, 0.29, 0.37 and 1.0 mm, respectively, with 100%
      sensitivities and specificities for common superficial temporal arteries, for
      frontal branches and for axillary arteries and sensitivities of 97.2 and 87.5%
      and specificities of 98.7 and 98.8% for parietal branches and facial arteries,
      respectively. The intraclass correlation coefficient was between 0.87 and 0.98.
      Conclusion: IMT measurement can correctly distinguish vasculitic from normal
      arteries in suspected GCA.

PMID- 28431107
TI  - Double fixation for abdominal aortic aneurysm repair using AFX body and Endurant
      proximal aortic cuff: mid-term results.
AB  - Our goal was to evaluate the use of an AFX main body combined with an Endurant
      proximal aortic cuff to treat selected patients with an abdominal aortic aneurysm
      (AAA) associated with anatomical challenges, such as a small distal aortic
      diameter and a hostile aortic neck. A retrospective analysis of prospectively
      collected data from 2 vascular institutions identified 14 elective patients with
      an AAA (all men, 73.5 +/- 5.1 years) treated with the AFX main body combined with
      an Endurant proximal aortic cuff. Patients had a small distal aortic diameter
      (median 19 mm) and a short or angulated proximal aortic neck (median length 20
      mm, range 9-26 mm, median angulation 41.5 degrees , range 23-80 degrees ). Six
      patients (42.9%) had an aortic neck that did not meet the indications for use of
      the AFX proximal aortic cuff. Primary technical success was achieved in all
      patients with no 30-day device-related complications or deaths. During a median
      follow-up period of 13 months (range 6-28 months), no re-intervention was needed.
      The diameter of the aneurysmal sac decreased from 57.6 +/- 5.6 mm preoperatively
      to 50.4 +/- 4.9 mm (P < 0.001) postoperatively. There were no aneurysm-related
      deaths or ruptures. No migration, disconnection or type I or III endoleak was
      observed. In 5 of the 6 patients, the initial type II endoleak spontaneously
      resolved during follow-up, whereas that in the remaining patient persisted
      without any change in the diameter of the aneurysmal sac. In patients with
      complex AAA anatomical configurations combining a hostile aortic neck and a
      narrow aortic bifurcation, the use of an AFX main body combined with an Endurant
      proximal aortic cuff seems to be feasible with favourable mid-term results.

PMID- 28431108
TI  - Investments in children's health and the Kenyan cash transfer for orphans and
      vulnerable children: evidence from an unconditional cash transfer scheme.
AB  - Child mortality is one of the most pressing global health and policy issues in
      the developing world. The leading drivers of death-pneumonia, diarrhea and
      malaria-are preventable and treatable. However, these illnesses are exacerbated
      by a lack of accessible nutrition, water, basic and preventive health services,
      and sanitary living conditions-all factors which are more likely to
      disproportionately impact the poor. We examine whether Kenya's largest social
      protection impacts children's incidence of upper respiratory illness. The Kenya
      Cash Transfer for Orphans and Vulnerable Children was designed to support orphans
      affected by HIV/AIDS and has covered over 240,000 households as of 2014. Using
      longitudinal, cluster-randomized program data from 2007 to 2009, we run a
      generalized linear latent and mixed method estimation model on a sample of
      children 0-7 years and under-5 years of age. We find that the program is
      associated with a decrease in illness in children 0-7 years of age (P < 0.05),
      but found no effects on a stratified sample of under-5 children. Furthermore, no
      impacts on health care seeking in the event of illness were detected. This study
      is one of few examining children's health using data from a large scale
      unconditional cash transfer program. With the widespread adoption of over 123
      cash transfer programs across sub-Saharan Africa, these findings suggest social
      cash transfer programs are capable of promoting the multidimensional well-being
      for the world's most vulnerable populations.

PMID- 28431109
TI  - Performance of the 2015 ACR-EULAR classification criteria for gout in a primary
      care population presenting with monoarthritis.
AB  - Objective: To test the performance of the 2015 ACR-EULAR gout classification
      criteria against presence of SF MSU crystals in a primary healthcare population.
      Methods: The criteria were applied to an existing dataset of consecutive patients
      with monoarthritis presenting to Dutch family physicians; all patients underwent
      microscopic SF analysis by design. The data had been prospectively collected to
      develop a diagnostic decision rule for gout in 2010. Diagnostic performance was
      assessed by calculating area under the receiver operating characteristic curve,
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and constructing calibration plots for the full version of the
      criteria (including SF analysis results of all patients) and the clinical-only
      version (not including SF analysis results). Performance of both versions was
      compared with the 2010 diagnostic rule. Results: Of 381 patients enrolled into
      the study, 216 (57%) were MSU crystal-positive. The full and clinical-only
      versions of the criteria had satisfactory area under the receiver operating
      characteristic curve (0.96 and 0.87, respectively), high specificity (0.98 and
      0.84), high PPV (0.98 and 0.84), but lower sensitivity (0.68 and 0.68) and NPV
      (0.70 and 0.67). Specificity and PPV of both versions were higher compared with
      0.71 and 0.89 of the 2010 diagnostic decision rule. The decison rule had the
      highest sensitivity and NPV (0.99 and 0.97). Conclusion: This study presents the
      first external validation of the 2015 ACR-EULAR gout classification criteria in a
      primary healthcare setting. The criteria perform well in this setting in patients
      presenting with monoarthritis for the purpose of enrolling into gout clinical
      trials.

PMID- 28431110
TI  - African histoplasmosis: new clinical and microbiological insights.
AB  - African histoplasmosis is defined as the fungal infection caused by Histoplasma
      capsulatum var. duboisii (Hcd). Studies focused on distinguishing Hcd and H.
      capsulatum var. capsulatum (Hcc), which coexist in Africa, are scarce or
      outdated, and African strains are continuously underrepresented. In this work, 13
      cases of African patients with histoplasmosis diagnosed in the Spanish Mycology
      Reference Laboratory have been reviewed showing that 77% had disseminated disease
      and AIDS as underlying disease although Hcd infection has been classically
      considered a rare presentation in AIDS patients. Strains isolated from these
      patients and other clinical and reference strains were studied by assessing
      classical identification methods and performing a three-loci multi-locus sequence
      analysis (MLSA). Classical identification methods based on biochemical tests and
      measurement of yeast size proved to be useless in distinguishing both varieties.
      The MLSA defined an African cluster, with a strong statistical support, that
      included all strains with African origin. Finally, mating type was also
      determined by using molecular methods revealing an unequal mating type
      distribution in African strains. In conclusion, historical statements and
      classical identification methods were useless to distinguish between varieties,
      whereas molecular analyses revealed that all strains with African origin grouped
      together suggesting that traditional classification should be revised. Further
      investigation is required in order to unravel traditional concepts about Hcd
      infection and support results obtained in this work.

PMID- 28431111
TI  - Correction of abnormal B-cell subset distribution by interleukin-6 receptor
      blockade in polymyalgia rheumatica.
AB  - Objectives: The aim was to study lymphocyte subsets and circulating cytokines at
      diagnosis of PMR and after tocilizumab monotherapy. Methods: Eighteen untreated
      patients with PMR were included in a prospective study and received 3-monthly
      tocilizumab infusions without glucocorticoids. Lymphocyte subset distribution was
      assessed by flow cytometry and serum cytokines were assayed by a 34-cytokine
      array and ELISA, at baseline and during follow-up. Baseline data were also
      compared with age- and sex-matched controls. Results: At baseline, total
      lymphocytes, T-cell subsets and NK cell counts were similar in patients and
      controls, but patients had significantly lower B-cell counts attributable to
      lower transitional, naive and post-switch memory B-cell subsets. Circulating B
      cell counts were positively correlated with the PMR activity score (PMR-AS) in
      untreated active patients at baseline, but subsequently increased to normal
      values while disease activity was controlled after tocilizumab therapy. Among
      serum cytokines, IL-6 showed the largest concentration difference between
      patients and controls, and the serum IL-6 concentration was correlated with
      baseline PMR-AS. The effects of tocilizumab on serum IL-6 concentration were
      heterogeneous, and the patients whose serum IL-6 decreased after tocilizumab
      therapy exhibited a significant increase in circulating B-cell counts.
      Conclusion: In patients with PMR, B-cell lymphopenia and abnormal B-cell subset
      distribution are associated with disease activity and IL-6 concentration, and
      both are corrected by the IL-6 antagonist tocilizumab.

PMID- 28431113
TI  - Proposing a health promotion framework to address gambling problems in Australian
      Indigenous communities.

PMID- 28431112
TI  - Long-term survival of the mouse ES cell-derived mast cell, MEDMC-BRC6, in mast
      cell-deficient KitW-sh/W-sh mice.
AB  - Mast cells (MCs) play pivotal roles in allergic reactions and the host defense
      against microbial infection through the IgE-dependent and IgE-independent
      signaling pathways. MC lines that can be analyzed both in vitro and in vivo would
      be useful for the study of MC-dependent immune responses. Here, we investigated
      the functional characteristics of a mouse embryonic stem cell-derived MC-like
      cell line, MEDMC-BRC6. The cell line expressed FcepsilonRI and c-Kit and showed
      degranulation and production of inflammatory cytokines and chemokines, including
      TNF-alpha, IL-6 and MCP-1, upon cross-linking FcepsilonRI with IgE. These
      cytokines and chemokines were also produced by the cell line by stimulation of
      TLR2 and TLR4. MEDMC-BRC6 survived in the peritoneal cavity and the ear skin for
      at least 6 months after the transfer into genetically compatible MC-deficient
      KitW-sh/W-sh mice, in which systemic anaphylaxis was successfully induced. Thus,
      MEDMC-BRC6 cells represent a potent tool for investigating the functions of MCs
      in vitro and in vivo.

PMID- 28431114
TI  - Molecular characterization of Cryptococcus neoformans isolated from the
      environment in Beijing, China.
AB  - The molecular type of environmental Cryptococcus neoformans in Beijing was not
      clear. Our study aims to reveal the molecular characterization of C. neoformans
      complex from environment in Beijing, China. A total of 435 samples of pigeon
      droppings from 11 different homes in Beijing were collected from August to
      November in 2015. Pigeon droppings were inoculated onto caffeic acid cornmeal
      agar (CACA) to screen C. neoformans complex. Bruker Biotyper matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was
      performed for species identification. Serotype and mating type was determined by
      specific primers. Restriction fragment length polymorphisms of URA5 (URA5-RFLP)
      were applied to genotype. Multi-locus sequence typing (MLST) was done for further
      identification and sequence type (ST) determination. Altogether, 81 isolates of
      C. neoformans AFLP1/VNI were recognized from 435 pigeon droppings in this study.
      The positive rate for C. neoformans AFLP1/VNI from pigeon droppings in different
      homes varied from 5.0% to 52.6%, the average was 20.2%. All of these cryptococcal
      strains were serotype A, MATalpha. They were genotyped as VNI by URA5-RFLP and
      were confirmed by MLST. No other molecular types of C. neoformans and
      Cryptococcus gattii isolates were isolated. Their STs were identified as ST 31 (n
      = 54, 66.7%), followed by ST 53 (n = 10), ST 191 (n = 8), ST 5 (n = 5), ST 57 (n
      = 3), and ST 38 (n = 1). We concluded that not only clinical but also
      environmental isolates of C. neoformans need to be investigated more deeply and
      more extensively. The virulence difference between ST 5 and ST 31 need to be
      explored in the future.

PMID- 28431116
TI  - Ontogeny and Thermogenic Role for Sternal Fat in Female Sheep.
AB  - Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a
      critical role in preventing hypothermia in newborn sheep but is then thought to
      rapidly disappear during postnatal life. The extent to which the anatomical
      location of fat influences postnatal development and thermogenic function in
      adulthood, particularly following feeding, is unknown, and we examined both in
      our study. Changes in gene expression of functionally important pathways (i.e.,
      thermogenesis, development, adipogenesis, and metabolism) were compared between
      sternal and retroperitoneal fat depots together with a representative skeletal
      muscle over the first month of postnatal life, coincident with the loss of brown
      fat and the accumulation of white fat. In adult sheep, implanted temperature
      probes were used to characterize the thermogenic response of fat and muscle to
      feeding and the effects of reduced or increased adiposity. UCP1 was more abundant
      in sternal fat than in retroperitoneal fat and was retained only in the sternal
      depot of adults. Distinct differences in the abundance of gene pathway markers
      were apparent between tissues, with sternal fat exhibiting some similarities with
      muscle that were not apparent in the retroperitoneal depot. In adults, the
      postprandial rise in temperature was greater and more prolonged in sternal fat
      than in retroperitoneal fat and muscle, a difference that was maintained with
      altered adiposity. In conclusion, sternal adipose tissue retains UCP1 into
      adulthood, when it shows a greater thermogenic response to feeding than do muscle
      and retroperitoneal fat. Sternal fat may be more amenable to targeted
      interventions that promote thermogenesis in large mammals.

PMID- 28431115
TI  - Spatial Distribution of Falciparum Malaria Infections in Zanzibar: Implications
      for Focal Drug Administration Strategies Targeting Asymptomatic Parasite
      Carriers.
AB  - Background: Optimal use of mass/targeted screen-and-treat or mass or focal drug
      administration as malaria elimination strategies remains unclear. We therefore
      studied spatial distribution of Plasmodium falciparum infections to compare
      simulated effects of these strategies on reducing the parasite reservoir in a pre
      elimination setting. Methods: P. falciparum rapid diagnostic tests (RDTs) and
      molecular (polymerase chain reaction [PCR]) and serological (enzyme-linked
      immunosorbent assay) analyses were performed on finger-prick blood samples from a
      population-based survey in 3 adjacent communities. Results: Among 5278 persons
      screened, 13 (0.2%) were positive by RDT and 123 (2.3%) by PCR. PCR-positive
      individuals were scattered over the study area, but logistic regression analysis
      suggested a propensity of these infections to cluster around RDT-positive
      individuals. The odds ratios for being PCR positive was 7.4 (95% confidence
      interval, 2.8-19.9) for those living in the household of an RDT-positive
      individual and 1.64 (1.0-2.8; P = .06) for those living within <300 m, compared
      with >1000 m. Treating everyone within households of RDT-positive individuals (1%
      population) would target 13% of those who are PCR positive. Treating all living
      within a radius of <300 or <1000 m (14% or 58% population) would target 30% or
      66% of infections, respectively. Among 4431 serologically screened individuals,
      26% were seropositive. Treating everyone within seropositive households (63%
      population) would target 77% of PCR-positive individuals. Conclusions:
      Presumptive malaria treatment seemed justified within RDT-positive households and
      potentially worth considering within, for example, a radius of <300 m. Serology
      was not discriminative enough in identifying ongoing infections for improving
      focal interventions in this setting but may rather be useful to detect larger
      transmission foci.

PMID- 28431117
TI  - Seeking Certainty? Judicial Approaches to the (Non-)Treatment of Minimally
      Conscious Patients.
AB  - A modest, but growing, body of case law is developing around the (non-)treatment
      of patients in the minimally conscious state. We sought to explore the approaches
      that the courts take to these decisions. Using the results of a qualitative
      analysis, we identify five key features of the rulings to date. First, the judges
      appear keen to frame the cases in such a way that these are rightly matters for
      judicial determination. Secondly, the judges appraise the types and forms of
      expertise that enter the courtroom, seeming to prefer the 'objective' and
      'scientific', and particularly the views of the doctors. Thirdly, the judges
      appear alert to the reasonableness of the evidence (and, indeed, the parties) and
      will look favourably on parties who are willing to co-operate. But the judges
      will not simply endorse any consensus reached by the parties; rather, the judges
      will reach their own decisions. Those decisions must be taken in the best
      interests of the patient. Fourthly, the judges approach this assessment in
      different ways. A balancing exercise is not consistently undertaken and, even in
      those cases in which it is, the weight accorded to particular factors varies. As
      we discuss, the consistency and predictability of the law in this area is open to
      question. Finally, however, we cautiously suggest that some consistent messages
      do begin to emerge: the courts' apparent preference for certainty in diagnosis
      and prognosis provide pointers for how cases might be decided.

PMID- 28431119
TI  - Survival benefit of adding docetaxel, cisplatin, and 5-fluorouracil induction
      chemotherapy to concurrent chemoradiotherapy for locally advanced nasopharyngeal
      carcinoma with nodal Stage N2-3.
AB  - Background: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT
      AC) has been established as the standard of care in locally advanced
      nasopharyngeal carcinoma (LA-NPC). The survival benefit of induction chemotherapy
      (ICT) for LA-NPC remains controversial. We analyzed the efficacy and feasibility
      of docetaxel, cisplatin and 5-fluorouracil (TPF) ICT followed by CCRT for LA-NPC
      with nodal Stage N2-3. Methods: We performed a retrospective analysis of 28 LA
      NPC patients with nodal Stage N2-3 receiving induction TPF followed by CCRT (TPF
      group; n = 12) or CCRT-AC (CCRT group; n = 16) between October 2006 and May 2016.
      Results: The median follow-up periods were 36.4 (range 6.7-55.2) and 40.1 months
      (range 4.3-99.0) for the TPF and CCRT groups, respectively. One- and three-year
      overall survival for the TPF group vs. the CCRT group were 100% and 100% vs. 94%
      and 75%, respectively (P = 0.21). The cumulative one- and three-year incidences
      of locoregional recurrence or progression for the TPF group vs. the CCRT group
      were 10% and 21% vs. 16% and 32% (P = 0.49), and those of distant metastasis were
      0% and 0% vs. 26% and 26%, respectively (P = 0.08). The common Grade 3-4 acute
      toxicities were neutropenia, anorexia, febrile neutropenia, and stomatitis in the
      TPF group. The Grade 3-4 late toxicities did not differ significantly between the
      two groups. Conclusions: This study suggests that induction TPF followed by CCRT
      might reduce distant metastasis, so this combination may be feasible for the
      treatment of LA-NPC with nodal Stage N2-3.

PMID- 28431120
TI  - Solution structure of a reverse transcriptase recognition site of a LINE RNA from
      zebrafish.
AB  - Long interspersed nuclear element (LINE) is known to be transposed by reverse
      transcription using its RNA transcript. Recognition of the 3' stem-loop of LINE
      RNA by its reverse transcriptase (RT) is an important step of the
      retrotransposition. Our previous study revealed that the second G residue (G8) in
      the GGAUA loop of a 17mer LINE RNA from eel, UnaL2-17, is recognized by its RT
      and the U residue (U10) in the same loop is required to maintain the loop
      structure (Baba S, Kajikawa M, Okada N, Kawai G. Solution structure of an RNA
      stem-loop derived from the 3' conserved region of eel LINE UnaL2. RNA
      2004;10:1380-1387). ZfL2-2, a LINE from zebrafish, has the same 3' stem-loop with
      UnaL2 and ZfL2-1 has similar but distinct 3' stem-loop with an insertion which
      can form an additional stem-loop. Here, we determined the solution structure of
      the 34mer RT recognition site of the LINE RNA (ZfL2-1-34). It was found that ZfL2
      1-34 forms a hairpin with an internal loop, the tertiary structure of which is
      superimposed with that of ZfL2-2. It is noted that A10 and the inserted stem
      loop, starting with A12, in ZfL2-1-34 located at the positions corresponding to
      those of G8 and U10, respectively, in UnaL2-17. These results strongly suggest
      that the two LINEs share the similar recognition mechanism and the A10 in ZfL2-1
      34 is the determinant recognized by its RT.

PMID- 28431118
TI  - Combining Human Epigenetics and Sleep Studies in Caenorhabditis elegans: A Cross
      Species Approach for Finding Conserved Genes Regulating Sleep.
AB  - Study Objectives: We aimed to test a combined approach to identify conserved
      genes regulating sleep and to explore the association between DNA methylation and
      sleep length. Methods: We identified candidate genes associated with shorter
      versus longer sleep duration in college students based on DNA methylation using
      Illumina Infinium HumanMethylation450 BeadChip arrays. Orthologous genes in
      Caenorhabditis elegans were identified, and we examined whether their loss of
      function affected C. elegans sleep. For genes whose perturbation affected C.
      elegans sleep, we subsequently undertook a small pilot study to re-examine DNA
      methylation in an independent set of human participants with shorter versus
      longer sleep durations. Results: Eighty-seven out of 485,577 CpG sites had
      significant differential methylation in young adults with shorter versus longer
      sleep duration, corresponding to 52 candidate genes. We identified 34 C. elegans
      orthologs, including NPY/flp-18 and flp-21, which are known to affect sleep. Loss
      of five additional genes alters developmentally timed C. elegans sleep
      (B4GALT6/bre-4, DOCK180/ced-5, GNB2L1/rack-1, PTPRN2/ida-1, ZFYVE28/lst-2). For
      one of these genes, ZFYVE28 (also known as hLst2), the pilot replication study
      again found decreased DNA methylation associated with shorter sleep duration at
      the same two CpG sites in the first intron of ZFYVE28. Conclusions: Using an
      approach that combines human epigenetics and C. elegans sleep studies, we
      identified five genes that play previously unidentified roles in C. elegans
      sleep. We suggest sleep duration in humans may be associated with differential
      DNA methylation at specific sites and that the conserved genes identified here
      likely play roles in C. elegans sleep and in other species.

PMID- 28431121
TI  - StarBEAST2 Brings Faster Species Tree Inference and Accurate Estimates of
      Substitution Rates.
AB  - Fully Bayesian multispecies coalescent (MSC) methods like *BEAST estimate species
      trees from multiple sequence alignments. Today thousands of genes can be
      sequenced for a given study, but using that many genes with *BEAST is intractably
      slow. An alternative is to use heuristic methods which compromise accuracy or
      completeness in return for speed. A common heuristic is concatenation, which
      assumes that the evolutionary history of each gene tree is identical to the
      species tree. This is an inconsistent estimator of species tree topology, a worse
      estimator of divergence times, and induces spurious substitution rate variation
      when incomplete lineage sorting is present. Another class of heuristics directly
      motivated by the MSC avoids many of the pitfalls of concatenation but cannot be
      used to estimate divergence times. To enable fuller use of available data and
      more accurate inference of species tree topologies, divergence times, and
      substitution rates, we have developed a new version of *BEAST called StarBEAST2.
      To improve convergence rates we add analytical integration of population sizes,
      novel MCMC operators and other optimizations. Computational performance improved
      by 13.5* and 13.8* respectively when analyzing two empirical data sets, and an
      average of 33.1* across 30 simulated data sets. To enable accurate estimates of
      per-species substitution rates, we introduce species tree relaxed clocks, and
      show that StarBEAST2 is a more powerful and robust estimator of rate variation
      than concatenation. StarBEAST2 is available through the BEAUTi package manager in
      BEAST 2.4 and above.

PMID- 28431122
TI  - The SENSE Study: Treatment Mechanisms of a Cognitive Behavioral and Mindfulness
      Based Group Sleep Improvement Intervention for At-Risk Adolescents.
AB  - Objectives: The aim of this study was to test whether a cognitive behavioral and
      mindfulness-based group sleep intervention would improve sleep and anxiety on
      school nights in a sample of at-risk adolescents. We also examined whether
      benefits to sleep and anxiety would be mediated by improvements in sleep hygiene
      awareness and presleep hyperarousal. Methods: Secondary analysis of a randomized
      controlled trial conducted with 123 adolescent participants (female = 60%; mean
      age = 14.48) who had high levels of sleep problems and anxiety symptoms.
      Participants were randomized into a sleep improvement intervention (n = 63) or
      active control "study skills" intervention (n = 60). Preintervention and
      postintervention, participants completed the Pittsburgh Sleep Quality Index
      (PSQI), Spence Children's Anxiety Scale (SCAS), Sleep Beliefs Scale (SBS), and
      Presleep Hyperarousal Scale (PSAS) and wore an actiwatch and completed a sleep
      diary for five school nights. Results: The sleep intervention condition was
      associated with significantly greater improvements in actigraphy-measured sleep
      onset latency (SOLobj), sleep diary measured sleep efficiency (SEsubj), PSQI,
      SCAS, SBS, and PSAS, with medium to large effect sizes. Improvements in the PSQI
      and SCAS were specifically mediated by the measured improvements in the PSAS that
      resulted from the intervention. Improvements in SOLobj and SEsubj were not
      specifically related to improvements in any of the putative treatment mechanisms.
      Conclusions: This study provides evidence that presleep arousal but not sleep
      hygiene awareness is important for adolescents' perceived sleep quality and could
      be a target for new treatments of adolescent sleep problems.

PMID- 28431123
TI  - Surgical intervention for ground glass dominant lesions: observation or outright
      resection?
AB  - Background: The management of ground glass opacity (GGO) on computed tomography
      (CT) remains controversial. Information of the relationship between clinical
      behavior and pathological invasiveness of GGO is valuable for management. We
      conducted this retrospective study to establish differences in the pathological
      invasiveness between GGO with and without changes. Methods: Among 1762 patients,
      the following criteria was used: (1) maximum tumor diameter of 3 cm or less, (2)
      tumor having 50% or more GGO and (3) resection after at least three months of
      follow up. A change of CT findings was defined as an increase in the diameter or
      consolidation compared with the initial CT. The relationship between preoperative
      changes and ratio of invasive adenocarcinoma was investigated. Predictors of GGO
      growth were also examined. Results: There were 250 patients: pure GGO without
      changes (G-N group; n = 118), pure GGO with changes (G-C group; n = 35), part
      solid GGO without changes (S-N group; n = 78), and part-solid GGO with changes (S
      C group; n = 20). The ratio of invasive adenocarcinoma in each group was 0.54,
      0.89, 0.8, and 0.90. There was a significant difference between the G-N and G-C
      group (P < 0.001). However, there was no significant difference between the G-C,
      S-N and S-C group. Multivariate analysis indicated age was a predictor of
      preoperative changes (OR = 1.953, P = 0.049). Conclusions: The pathological
      results of part-solid GGO with changes were not different from those without
      changes. Therefore surgery can be deferred until those lesions demonstrate
      changes. The pathological results of pure GGO with changes were equivalent to
      those of part-solid GGO. Therefore, even for pure GGO, follow up is necessary
      especially in elderly patients.

PMID- 28431124
TI  - Childhood vaccinations and risk of acute lymphoblastic leukaemia in children.
AB  - Background: It has been proposed that childhood vaccinations protect against
      acute lymphoblastic leukaemia (ALL) in children by modulation of future responses
      to common infections in childhood. However, the available studies provide
      inconsistent findings, and population-based cohort studies with longitudinal
      information on vaccinations are lacking. Methods: In a register-based cohort of
      all children born in Denmark from 1 January 1990 to 31 December 2008, followed up
      until age 15 years or 31 December 2009 ( n  = 1 225 404), we evaluated exposure
      to childhood vaccination and risk of childhood ALL, including information on ALL
      subtypes. Using Cox regression, we estimated hazard ratios (HRs) comparing
      vaccinated with unvaccinated children. Results: Childhood ALL was diagnosed in
      490 children during 10 829 194 person-years of follow-up. Neither the total
      number of vaccine doses received nor exposure to each vaccination given in
      childhood was associated with altered risk of ALL, including the following: (i)
      Haemophilus influenzae type b [HR, 1.04; 95% confidence interval (CI), 0.68
      1.61]; ii) measles, mumps and rubella (HR, 1.01; 95% CI, 0.76-1.34); iii) whole
      cell pertussis (HR, 1.10; 95% CI, 0.51-2.39); and iv) diphtheria, tetanus and
      inactivated polio (HR, 1.14; 95% CI, 0.42-3.13). Analyses conducted according to
      ALL subtypes defined by immunopheno- and karyotypes showed no association with
      childhood vaccination. Conclusions: This nationwide cohort study provides no
      support of the proposed protective effect of childhood vaccination against
      childhood ALL.

PMID- 28431125
TI  - Corrigendum.

PMID- 28431126
TI  - Vaccine Impact Data Should Support Country Decision Making.

PMID- 28431127
TI  - Cytomegalovirus Kinetics Following Primary Infection in Healthy Women.
AB  - The kinetics of cytomegalovirus (CMV) DNA in infected asymptomatic hosts are
      largely unknown. We measured viral load (VL) in 124 fluid samples (oral, urine,
      vaginal, blood) collected from 21 women who acquired CMV. A quantitative real
      time polymerase chain reaction assay of US17, which correlated with clinical
      assays, was used. VL decreased following primary infection in all fluids. The
      geometric mean VL of vaginal fluid was significantly higher than that of other
      sources: oral (3.89; 95% confidence interval [CI], 1.43-10.57), urine (6.36; 95%
      CI, 2.48-16.32), and whole blood (11.88; 95% CI, 4.12-34.20). Vaginal CMV
      shedding may provide a route for sexual and possibly perinatal transmission.

PMID- 28431128
TI  - Binge drinking and well-being in European older adults: do gender and region
      matter?
AB  - Background: We aimed to describe gender and region differences in the prevalence
      of binge drinking and in the association between binge drinking and well-being,
      among older adult Europeans. Methods: This is a cross-sectional study using the
      Survey of Health, Ageing and Retirement in Europe (SHARE) wave 4, conducted
      between 2011 and 2012, including 58 489 individuals aged 50 years or older.
      Sixteen European countries were grouped in four drinking culture regions: South,
      Central, North and East. We categorized drinking patterns as: never, former, no
      binge and binge drinkers. We used the CASP-12 questionnaire to measure well
      being. To assess the association between binge drinking and well-being, we fitted
      two-level mixed effects linear models. Results: The highest percentage of binge
      drinkers was found in Central Europe (17.25% in men and 5.05% in women) and the
      lowest in Southern Europe (9.74% in men and 2.34% in women). Former, never and
      binge drinkers had a significant negative association with well-being as compared
      with no-binge drinkers. There was a significant interaction in this association
      by gender and region. Overall, associations were generally stronger in women and
      in Southern and Eastern Europe. The negative association of binge drinking with
      well-being was especially strong in Southern European women (beta = -3.80, 95%
      CI: -5.16 to - 2.44, P value <0.001). Conclusion: In Southern and Eastern
      European countries the association between binge drinking and well-being is
      stronger, especially in women, compared with Northern and Central Europe.
      Cultural factors (such as tolerance to drunkenness) should be further explored.

PMID- 28431129
TI  - Cooled Radiofrequency Ablation of the Genicular Nerves for Chronic Pain due to
      Knee Osteoarthritis: Six-Month Outcomes.
AB  - Objective: Determine outcomes of cooled radiofrequency ablation (C-RFA) of the
      genicular nerves for treatment of chronic knee pain due to osteoarthritis (OA).
      Design: Cross-sectional survey. Setting: Academic pain medicine center. Subjects:
      Consecutive patients with knee OA and 50% or greater pain relief following
      genicular nerve blocks who underwent genicular nerve C-RFA. Methods: Survey
      administration six or more months after C-RFA. Pain numeric rating scale (NRS),
      Medication Quantification Scale III (MQSIII), Patient Global Impression of Change
      (PGIC), and total knee arthroplasty (TKA) data were collected. Logistic
      regression was used to identify factors that predicted treatment success.
      Results: Thirty-three patients (52 discrete knees) met inclusion criteria. Thirty
      five percent (95% confidence interval [CI] = 22-48) of procedures resulted in the
      combined outcome of 50% or greater reduction in NRS score, reduction of 3.4 or
      more points in MQSIII score, and PGIC score consistent with "very much
      improved/improved." Nineteen percent (95% CI = 10-33) of procedures resulted in
      complete pain relief. Greater duration of pain and greater than 80% pain relief
      from diagnostic blocks were identified as predictors of treatment success. The
      accuracy of the model was 0.88 (95% CI = 0.78-0.97, P  <   0.001). Conclusions:
      Genicular C-RFA demonstrated a success rate of 35% based on a robust combination
      of outcome measures, and 19% of procedures resulted in complete relief of pain at
      a minimum of six months of follow-up. Report of 80% or greater relief from
      diagnostic blocks and duration of pain of less than five years are associated
      with high accuracy in predicting treatment success. Further prospective study is
      needed to optimize the patient selection protocol and success rate of this
      procedure.

PMID- 28431130
TI  - Safety Concerns with Thoracoabdominal Acupuncture: Experience at a Tertiary-Care
      Emergency Department.
AB  - Objective: To evaluate serious complications caused by acupuncture treatment and
      to increase awareness of this complication. Design: A retrospective observational
      study. Setting: At the emergency department of a tertiary hospital in an urban
      area during a five-year period (2010-2014) in Seoul, Korea. Subjects: Patients
      with postacupuncture mechanical complications in the thoracoabdominal region.
      Methods: All cases were independently assessed for inclusion by two emergency
      physicians based on the causal relationship between acupuncture and emergency
      department presentation. Results: There were 10 cases of pneumothorax (one
      combined with pneumomediastinum) and two cases of pneumoperitoneum induced by
      acupuncture. Five of the 12 patients were male; the mean age was 43.4 years. The
      mean time between acupuncture and emergency department admission was 1.6 days.
      The pneumothorax was unilateral in eight cases and bilateral in two. Eight
      patients underwent tube thoracostomy (pig tail catheter or chest tube insertion)
      and were admitted to the hospital for a median of 11 days. Of the two patients
      with pneumoperitoneum, one was transferred to another hospital for emergency
      surgery and the other was admitted to our hospital after emergency total
      colectomy. Conclusions: Life-threating complications such as pneumothorax and
      bowel perforation after acupuncture can occur, and this suggests that physicians,
      especially acupuncturists, should be aware of the risk associated with needling
      around the trunk region. To maximize the safety of acupuncture, adequate
      competency-based training should be provided.

PMID- 28431131
TI  - DNAproDB: an interactive tool for structural analysis of DNA-protein complexes.
AB  - Many biological processes are mediated by complex interactions between DNA and
      proteins. Transcription factors, various polymerases, nucleases and histones
      recognize and bind DNA with different levels of binding specificity. To
      understand the physical mechanisms that allow proteins to recognize DNA and
      achieve their biological functions, it is important to analyze structures of DNA
      protein complexes in detail. DNAproDB is a web-based interactive tool designed to
      help researchers study these complexes. DNAproDB provides an automated structure
      processing pipeline that extracts structural features from DNA-protein complexes.
      The extracted features are organized in structured data files, which are easily
      parsed with any programming language or viewed in a browser. We processed a large
      number of DNA-protein complexes retrieved from the Protein Data Bank and created
      the DNAproDB database to store this data. Users can search the database by
      combining features of the DNA, protein or DNA-protein interactions at the
      interface. Additionally, users can upload their own structures for processing
      privately and securely. DNAproDB provides several interactive and customizable
      tools for creating visualizations of the DNA-protein interface at different
      levels of abstraction that can be exported as high quality figures. All
      functionality is documented and freely accessible at http://dnaprodb.usc.edu.

PMID- 28431132
TI  - Revealing the Biochemical and Genetic Basis of Color Variation in a Polymorphic
      Lizard.
AB  - Determining the mechanistic and genetic basis of animal coloration is essential
      to understand the costs and constraints on color production, and the evolution
      and maintenance of phenotypic variation. However, genes underlying structural
      color and widespread pigment classes apart from melanin remain largely
      uncharacterized, in part due to restricted taxonomic focus. We combined liquid
      chromatography-mass spectrometry and RNA-seq gene expression analyses to
      characterize the pigments and genes associated with skin color in the polymorphic
      lizard, Ctenophorus decresii. Throat coloration in male C. decresii may be a
      combination of orange, yellow, grey, or ultra-violet blue. We confirmed the
      presence of two biochemically different pigment classes, pteridines (self
      synthesized) and carotenoids (acquired through the diet), in all skin colors.
      Orange skin had the highest levels of pteridine pigments while yellow skin tended
      to have higher levels of carotenoids, of which the vitamin A precursors beta
      carotene and beta-cryptoxanthin have not been previously confirmed in reptiles.
      These results were confirmed by gene expression analyses, which detected 489
      genes differentially expressed between the skin colors, including genes
      associated with pteridine production, provitamin A carotenoid metabolism,
      iridophore-specific synthesis, melanin synthesis, and steroid hormone pathways.
      For the majority of these 489 genes, however, our study reveals a new association
      with color production in vertebrates. These data represent a significant
      contribution to understanding the genetic basis of color variation in vertebrates
      and a rich resource for further studies.

PMID- 28431133
TI  - Prediction of sudden and non-sudden cardiac death in post-infarction patients
      with reduced left ventricular ejection fraction by periodic repolarization
      dynamics: MADIT-II substudy.
AB  - Aims: To test the value of Periodic Repolarization Dynamics (PRD), a recently
      validated electrocardiographic marker of sympathetic activity, as a novel
      approach to predict sudden cardiac death (SCD) and non-sudden cardiac death (N
      SCD) and to improve identification of patients that profit from ICD-implantation.
      Methods and results: We included 856 post-infarction patients with left
      ventricular ejection fraction (LVEF) <=30% of the MADIT-II trial in sinus rhythm.
      Of these, 507 and 348 patients were randomized to ICD or conventional treatment.
      PRD was assessed from multipolar 10-min baseline ECGs. Primary and secondary
      endpoints were total mortality, SCD and N-SCD. Multivariable analyses included
      treatment group, QRS-duration, New York Heart Association classification, blood
      urea nitrogen, diabetes mellitus, beta-blocker therapy and LVEF. During follow-up
      of 20.4 months, 119 patients died (53 SCD and 36 N-SCD). On multivariable
      analyses, increased PRD was a significant predictor of mortality (standardized
      coefficient 1.37[1.19-1.59]; P < 0.001) and SCD (1.40 [1.13-1.75]; P = 0.003) but
      also predicted N-SCD (1.41[1.10-1.81]; P = 0.006). While increased PRD predicted
      SCD in conventionally treated patients (1.61[1.23-2.11]; P < 0.001), it was
      predictive of N-SCD (1.63[1.28-2.09]; P < 0.001) and adequate ICD-therapies
      (1.20[1.03-1.39]; P = 0.017) in ICD-treated patients. ICD-treatment substantially
      reduced mortality in the lowest three PRD-quartiles by 53% (P = 0.001). However,
      there was no effect in the highest PRD-quartile (mortality increase by 29%; P =
      0.412; P < 0.001 for difference) as the reduction of SCD was compensated by an
      increase of N-SCD. Conclusion: In post-infarction patients with impaired LVEF,
      PRD is a significant predictor of SCD and N-SCD. Assessment of PRD is a promising
      tool to identify post-MI patients with reduced LVEF who might benefit from
      intensified treatment.

PMID- 28431134
TI  - Floral transitions in wheat and barley: interactions between photoperiod, abiotic
      stresses, and nutrient status.
AB  - The timing of plant reproduction has a large impact on yield in crop plants.
      Reproductive development in temperate cereals comprises two major developmental
      transitions. During spikelet initiation, the identity of the shoot meristem
      switches from the vegetative to the reproductive stage and spikelet primordia are
      formed on the apex. Subsequently, floral morphogenesis is initiated, a process
      strongly affected by environmental variation. Recent studies in cereal grasses
      have suggested that this later phase of inflorescence development controls floret
      survival and abortion, and is therefore crucial for yield. Here, we provide a
      synthesis of the early morphological and the more recent genetic studies on shoot
      development in wheat and barley. The review explores how photoperiod, abiotic
      stress, and nutrient signalling interact with shoot development, and pinpoints
      genetic factors that mediate development in response to these environmental cues.
      We anticipate that research in these areas will be important in understanding
      adaptation of cereal grasses to changing climate conditions.

PMID- 28431136
TI  - C1 Lateral Mass Displacement and Transverse Atlantal Ligament Failure in
      Jefferson's Fracture: A Biomechanical Study of the "Rule of Spence".
AB  - BACKGROUND: Jefferson's fracture, first described in 1927, represents a bursting
      fracture of the C1 ring with lateral displacement of the lateral masses. It has
      been determined that if the total lateral mass displacement (LMD) exceeds 6.9 mm,
      there is high likelihood of transverse atlantal ligament (TAL) rupture, and if
      LMD is less than 5.7 mm TAL injury is unlikely. Several recent radiographic
      studies have questioned the accuracy and validity of the "rule of Spence" and it
      lacks biomechanical support. OBJECTIVE: To determine the amount of LMD necessary
      for TAL failure using modern biomechanical techniques. METHODS: Using a universal
      material testing machine, cadaveric TALs were stretched laterally until failure.
      A high-resolution, high-speed camera was utilized to measure the displacement of
      the lateral masses upon TAL failure. RESULTS: Eleven cadaveric specimens were
      tested (n = 11). The average LMD upon TAL failure was 3.2 mm (+/-1.2 mm). The
      average force required to cause failure of the TAL was 242 N (+/-82 N). From our
      data analysis, if LMD exceeds 3.8 mm, there is high probability of TAL failure.
      CONCLUSION: Our findings suggest that although the rule of Spence is a
      conceptually valid measure of TAL integrity, TAL failure occurs at a
      significantly lower value than previously reported (P < .001). Based on our
      literature review and findings, LMD is not a reliable independent indicator for
      TAL failure and should be used as an adjunctive tool to magnetic resonance
      imaging rather an absolute rule.

PMID- 28431135
TI  - Reconstitution of a functional 7SK snRNP.
AB  - The 7SK small nuclear ribonucleoprotein (snRNP) plays a central role in RNA
      polymerase II elongation control by regulating the availability of active P-TEFb.
      We optimized conditions for analyzing 7SK RNA by SHAPE and demonstrated a
      hysteretic effect of magnesium on 7SK folding dynamics including a 7SK GAUC motif
      switch. We also found evidence that the 5? end pairs alternatively with two
      different regions of 7SK giving rise to open and closed forms that dictate the
      state of the 7SK motif. We then used recombinant P-TEFb, HEXIM1, LARP7 and MEPCE
      to reconstruct a functional 7SK snRNP in vitro. Stably associated P-TEFb was
      highly inhibited, but could still be released and activated by HIV-1 Tat.
      Notably, P-TEFb association with both in vitro-reconstituted and cellular snRNPs
      led to similar changes in SHAPE reactivities, confirming that 7SK undergoes a P
      TEFb-dependent structural change. We determined that the xRRM of LARP7 binds to
      the 3? stem loop of 7SK and inhibits the methyltransferase activity of MEPCE
      through a C-terminal MEPCE interaction domain (MID). Inhibition of MEPCE is
      dependent on the structure of the 3? stem loop and the closed form of 7SK RNA.
      This study provides important insights into intramolecular interactions within
      the 7SK snRNP.

PMID- 28431137
TI  - TRAPP webserver: predicting protein binding site flexibility and detecting
      transient binding pockets.
AB  - The TRAnsient Pockets in Proteins (TRAPP) webserver provides an automated
      workflow that allows users to explore the dynamics of a protein binding site and
      to detect pockets or sub-pockets that may transiently open due to protein
      internal motion. These transient or cryptic sub-pockets may be of interest in the
      design and optimization of small molecular inhibitors for a protein target of
      interest. The TRAPP workflow consists of the following three modules: (i) TRAPP
      structure- generation of an ensemble of structures using one or more of four
      possible molecular simulation methods; (ii) TRAPP analysis-superposition and
      clustering of the binding site conformations either in an ensemble of structures
      generated in step (i) or in PDB structures or trajectories uploaded by the user;
      and (iii) TRAPP pocket-detection, analysis, and visualization of the binding
      pocket dynamics and characteristics, such as volume, solvent-exposed area or
      properties of surrounding residues. A standard sequence conservation score per
      residue or a differential score per residue, for comparing on- and off-targets,
      can be calculated and displayed on the binding pocket for an uploaded multiple
      sequence alignment file, and known protein sequence annotations can be displayed
      simultaneously. The TRAPP webserver is freely available at http://trapp.h
      its.org.

PMID- 28431139
TI  - Massive aortic valve thrombosis with free floating thrombus following
      transcatheter aortic valve replacement.

PMID- 28431138
TI  - Cardiovascular outcome trials in patients with chronic kidney disease: challenges
      associated with selection of patients and endpoints.
AB  - Although cardiovascular disease is a major health burden for patients with
      chronic kidney disease, most cardiovascular outcome trials have excluded patients
      with advanced chronic kidney disease. Moreover, the major cardiovascular outcome
      trials that have been conducted in patients with end-stage renal disease have not
      demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide
      the management of cardiovascular disease in patients with chronic kidney disease,
      particularly those on dialysis. Several factors contribute to both the paucity of
      trials and the apparent lack of observed treatment effect in completed studies.
      Challenges associated with conducting trials in this population include patient
      heterogeneity, complexity of renal pathophysiology and its interaction with
      cardiovascular disease, and competing risks for death. The Investigator Network
      Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an
      international organization of academic cardiovascular and renal clinical
      trialists, held a meeting of regulators and experts in nephrology, cardiology,
      and clinical trial methodology. The group identified several research priorities,
      summarized in this paper, that should be pursued to advance the field towards
      achieving improved cardiovascular outcomes for these patients. Cardiovascular and
      renal clinical trialists must partner to address the uncertainties in the field
      through collaborative research and design clinical trials that reflect the
      specific needs of the chronic and end-stage kidney disease populations, with the
      shared goal of generating robust evidence to guide the management of
      cardiovascular disease in patients with kidney disease.

PMID- 28431141
TI  - Grade and location of power Doppler are predictive of damage progression in
      rheumatoid arthritis patients in clinical remission by anti-tumour necrosis
      factor alpha.
AB  - Objectives: To investigate power Doppler (PD) signal, grade and location and
      their association with radiographic progression in RA patients in remission.
      Methods: A prospective observational study was conducted in 125 consecutive RA
      patients in stable 28-joint DAS (DAS28) remission (?6 months) achieved on anti
      TNF-alpha. At baseline, patients in stable remission underwent radiographic and
      US examination of the wrists and MCP, PIP and MTP joints. Semi-quantitative PD
      scoring (0-3) was recorded. We scored PD according to two locations: capsular or
      within synovial tissue without bone contact (location 1) and with bone contact or
      penetrating bone cortex (location 2). Radiographic progression was evaluated at
      the 1 year follow-up and defined as a change in van der Heijde-modified total
      Sharp score >0. Risk ratios (RRs) of radiographic progression according to
      presence, grade and location of PD were calculated. Results: Four patients were
      excluded because of missing data. At baseline, 59/121 (48.7%) patients had a PD
      signal in one or more joints. PD location 2 was found in 74.6% patients (44/59).
      At the 1 year follow-up, 17/121 patients experienced radiographic progression:
      all had PD signal in one or more joints at baseline (RR 2.47, P < 0.0001).
      Radiographic progression was associated with the following baseline US features:
      PD grade 2 (RR 4.58, P < 0.01), PD grade 3 (RR 3.49, P < 0.05), total PD score ?2
      (sum of all PD scores) (RR 3.19, P < 0.0001) and PD location 2 (RR 3.49, P <
      0.0001). Conclusion: Higher PD grades and PD in contact with/or penetrating bone
      are associated with radiographic progression in patients in DAS28 remission.

PMID- 28431140
TI  - Performance of the Patient-Reported Outcomes Measurement Information System-29 in
      scleroderma: a Scleroderma Patient-centered Intervention Network Cohort Study.
AB  - Objective: The Patient-Reported Outcomes Measurement Information System (PROMIS)
      29 assesses seven health-related quality of life domains plus pain intensity. The
      objective was to examine PROMIS-29v2 validity and explore clinical associations
      in patients with SSc. Methods: English-speaking SSc patients in the Scleroderma
      Patient-centered Intervention Network Cohort from 26 sites in Canada, the USA and
      the UK completed the PROMIS-29v2 between July 2014 and November 2015. Enrolling
      physicians provided medical data. To examine convergent validity, hypotheses on
      the direction and magnitude of correlations with legacy measures were tested. For
      clinical associations, t -tests were conducted for dichotomous variables and
      PROMIS-29v2 domain scores. Effect sizes (ESs) were labelled as small (<0.25),
      small to moderate (0.25-0.45), moderate (0.46-0.55), moderate to large (0.56
      0.75) and large (>0.75). Results: There were 696 patients (87% female), mean ( s
      . d .) disease duration 11.6 (8.7) years, 57% with limited cutaneous subtype.
      Validity indices were consistent with seven of nine hypotheses (| r | =0.51-0.87,
      P < 0.001), with minor divergence for two hypotheses. Gastrointestinal
      involvement was associated with significantly worse outcomes for all eight PROMIS
      29v2 domains (moderate or moderate to large ES in six of eight). Presence of
      joint contractures was associated with significant decrements in seven domains
      (small or small to moderate ESs). Skin thickening, diffuse cutaneous subtype and
      presence of overlap syndromes were significantly associated (small or small to
      moderate ESs) with five or six domains. Conclusion: This study further
      establishes the validity of the PROMIS-29v2 in SSc and underlines the importance
      of gastrointestinal symptoms and joint contractures in reduced health-related
      quality of life.

PMID- 28431143
TI  - Characterisation of the gill mucosal bacterial communities of four butterflyfish
      species: a reservoir of bacterial diversity in coral reef ecosystems.
AB  - While recent studies have suggested that fish mucus microbiota play an important
      role in homeostasis and prevention of infections, very few studies have
      investigated the bacterial communities of gill mucus. We characterised the gill
      mucus bacterial communities of four butterflyfish species and although the
      bacterial diversity of gill mucus varied significantly between species, Shannon
      diversities were high (H = 3.7-5.7) in all species. Microbiota composition
      differed between butterflyfishes, with Chaetodon lunulatus and C. ornatissimus
      having the most similar bacterial communities, which differed significantly from
      C. vagabundus and C. reticulatus. The core bacterial community of all species
      consisted of mainly Proteobacteria followed by Actinobacteria and Firmicutes.
      Chaetodonlunulatus and C. ornatissimus bacterial communities were mostly
      dominated by Gammaproteobacteria with Vibrio as the most abundant genus.
      Chaetodonvagabundus and C. reticulatus presented similar abundances of
      Gammaproteobacteria and Alphaproteobacteria, which were well represented by
      Acinetobacter and Paracoccus, respectively. In conclusion, our results indicate
      that different fish species present specific bacterial assemblages. Finally, as
      mucus layers are nutrient hotspots for heterotrophic bacteria living in
      oligotrophic environments, such as coral reef waters, the high bacterial
      diversity found in butterflyfish gill mucus might indicate external fish mucus
      surfaces act as a reservoir of coral reef bacterial diversity.

PMID- 28431142
TI  - Respiratory chain enzyme deficiency induces mitochondrial location of actin
      binding gelsolin to modulate the oligomerization of VDAC complexes and cell
      survival.
AB  - Despite considerable knowledge on the genetic basis of mitochondrial disorders,
      their pathophysiological consequences remain poorly understood. We previously
      used two-dimensional difference gel electrophoresis analyses to define a protein
      profile characteristic for respiratory chain complex III-deficiency that included
      a significant overexpression of cytosolic gelsolin (GSN), a cytoskeletal protein
      that regulates the severing and capping of the actin filaments. Biochemical and
      immunofluorescence assays confirmed a specific increase of GSN levels in the
      mitochondria from patients' fibroblasts and from transmitochondrial cybrids with
      complex III assembly defects. A similar effect was obtained in control cells upon
      treatment with antimycin A in a dose-dependent manner, showing that the enzymatic
      inhibition of complex III is sufficient to promote the mitochondrial localization
      of GSN. Mitochondrial subfractionation showed the localization of GSN to the
      mitochondrial outer membrane, where it interacts with the voltage-dependent anion
      channel protein 1 (VDAC1). In control cells, VDAC1 was present in five stable
      oligomeric complexes, which showed increased levels and a modified distribution
      pattern in the complex III-deficient cybrids. Downregulation of GSN expression
      induced cell death in both cell types, in parallel with the specific accumulation
      of VDAC1 dimers and the release of mitochondrial cytochrome c into the cytosol,
      indicating a role for GSN in the oligomerization of VDAC complexes and in the
      prevention of apoptosis. Our results demonstrate that respiratory chain complex
      III dysfunction induces the physiological upregulation and mitochondrial location
      of GSN, probably to promote cell survival responses through the modulation of the
      oligomeric state of the VDAC complexes.

PMID- 28431144
TI  - Effect of Body Mass Index on Venous Sinus Pressures in Idiopathic Intracranial
      Hypertension Patients Before and After Endovascular Stenting.
AB  - BACKGROUND: Elevated body mass index (BMI) has been correlated with worse
      outcomes after treatment for idiopathic intracranial hypertension (IIH). Venous
      sinus stenting (VSS) has emerged as a safe and effective treatment for a subset
      of patients with IIH and evidence of venous sinus stenosis. However, the
      association between BMI and the efficacy of VSS remains poorly characterized.
      OBJECTIVE: To determine, in a retrospective cohort study, the effect of BMI on
      preoperative mean intracranial venous pressure (MVP) and post-VSS outcomes.
      METHODS: We performed a retrospective evaluation of a prospectively collected
      database of patients with IIH and intracranial venous sinus stenosis who
      underwent VSS. Patient demographics and treatment factors, including pre- and
      postprocedural trans-stenosis pressure gradients, were analyzed to identify the
      relationship between BMI and outcomes after VSS. RESULTS: Increasing BMI was
      significantly correlated with higher maximum MVP (P = .013) and higher trans
      stenosis pressure gradient (P = .043) prior to treatment. The degrees of
      improvement in maximum MVP and pressure gradient after VSS were greatest for
      obese and morbidly obese patients (BMI > 30 kg/m2). Maximum poststent MVP,
      clinical outcomes, and stent-adjacent stenosis requiring retreatment after VSS
      were not significantly associated with BMI. CONCLUSION: We provide direct
      evidence for a positive correlation between BMI and intracranial venous pressure
      in patients with IIH. VSS affords a significantly greater amelioration of
      intracranial venous hypertension and stenosis for IIH patients with higher BMIs.
      As such, obesity should not be a deterrent for the use of VSS in the management
      of IIH.

PMID- 28431145
TI  - Long-term effects of a lifestyle intervention and oral glucosamine sulphate in
      primary care on incident knee OA in overweight women.
AB  - Objectives: The present study was designed to evaluate the effect of a lifestyle
      intervention aimed to reduce body weight and of oral glucosamine sulphate on the
      incidence of knee osteoarthritis (OA) after 6-7 years in a population of middle
      aged, overweight women, without knee OA at baseline. Methods: The Prevention of
      knee Osteoarthritis in Overweight Females study, ISRCTN42823086, was a randomized
      controlled trial with a 2 * 2 factorial design. Four hundred and seven women aged
      50-60 years with a BMI of ?27 kg/m 2 and free of knee OA were randomized.
      Results: Four hundred and seventy-seven knees from 245 participants were
      available after a mean follow-up time of 6.6 years. Nineteen per cent of all
      knees showed incident knee OA. Both interventions showed no significant
      preventive effect on incident knee OA. Despite the fact that per protocol
      analyses showed greater differences between both groups for the lifestyle
      intervention, significance was not reached. A significant effect of losing ?5 kg
      or ? 5% of baseline weight in the first 12 months on the incidence of knee OA
      according to the primary outcome was found (odds ratio = 0.10; 95% CI: 0.02,
      0.41). Conclusion: No significant preventive effect on incident knee OA of either
      the lifestyle intervention or the glucosamine intervention was found. As a proof
      of concept, the preventive effect of moderate weight loss in 1 year on the
      incidence of clinical knee OA is demonstrated. This trial provides important
      insights for future studies on the prevention of knee OA, which are currently
      lacking. Trial registration: ISRTCN registry, http://www.isrctn.com ,
      ISRCTN42823086.

PMID- 28431146
TI  - Response of broiler chickens fed wheat-based diets to xylanase supplementation.
AB  - The objective of this study was to evaluate the effect of xylanase
      supplementation on performance, footpad score (FPS), nutrient digestibility, and
      intestinal morphometry in broiler chickens. Two-hundred-eighty-eight Ross 308
      broiler chicks (one d old) were placed in one of 3 experimental treatments:
      positive control (PC), negative control (NC) (-150 kcal/kg), and XYL (NC
      supplemented with xylanase). Each treatment had 8 replicates with 12 animals
      each. Starter (zero to 21 d) and grower (21 to 42 d) diets, based on wheat and
      soy-bean meal, were available ad libitum. Body weight gain (BWG) and feed intake
      were measured, and mortality corrected feed conversion ratio (FCR) was
      calculated. The relative weights of the empty gastrointestinal tract compartments
      and FPS were recorded on d 21 and d 42. On d 42, ileal contents were collected
      for nutrient digestibility determination. Statistical comparisons were performed
      using one-way ANOVA (JMP Pro 12). The reduction of energy resulted in lighter
      birds at the end of the study (PC: 2,710 vs. NC: 2,546 g; P = 0.030) whereas
      xylanase supplementation numerically increased BWG by 84 g (P = 0.229) and
      improved FCR by 12 points (P = 0.145) compared with the NC. Significant
      differences in FPS were observed on d 21. Score 0 (no lessions) was predominant
      in PC and XYL treatments, while score 1 (mild lesions) had a higher frequency in
      NC birds. Xylanase supplementation numerically increased organic matter (5.9%)
      and energy (4.7%) utilization with values above those observed with the NC. No
      treatment effects were observed in any of the morphometric measurements, with the
      exception of the gizzard (P = 0.036) and the ileum (P = 0.088) on d 42. Xylanase
      resulted in higher relative gizzard weights compared to NC (P = 0.102).
      Supplementation of broiler diets with xylanase tended to influence performance,
      which may be due to a better utilization of nutrients. The increase in gizzard
      and ileum weights in birds 42 d but not 21 d of age suggests an adaptive response
      that takes time to develop.

PMID- 28431147
TI  - Detection of epigenetic mutagens including anthracene-derived compounds using
      yeast FLO1 promoter GFP reporter gene assay.
AB  - Recently, we have reported that the FLO1-mediated flocculation levels of yeast
      are affected by an epigenetic mutagen, alizarin. Alizarin promoted flocculation
      and reduced the bulk levels of histone H3 in yeast cells. Since alizarin has been
      known to possess carcinogenesis-promoting properties, it is important to estimate
      the effect of alizarin-related compounds on epigenome as measured by the
      flocculation of yeast. In this study, we examined the effects of two anthracene
      derived compounds other than alizarin on the flocculation level of yeast.
      Purpurin significantly promoted the flocculation in a dose-dependent manner.
      While, quinizarin had a weaker promoting effect than purpurin. The strain treated
      with purprin showed FLO1 mRNA upregulation and reduced histone H3 expression
      similarly to alizarin. We also confirmed that the purprin-treated cells
      frequently exhibited abnormally shaped nuclei. Moreover, fluorescence intensities
      of green fluorescent protein (GFP) reporter under the FLO1 promoter control were
      dose-dependently increased by purprin and alizarin in the yeast. Taken together,
      these results suggest that the GFP reporter gene system utilising the FLO1
      promoter is useful for the detection of epigenetic mutagens including anthracene
      derived compounds.

PMID- 28431149
TI  - Next-generation non-starch polysaccharide-degrading, multi-carbohydrase complex
      rich in xylanase and arabinofuranosidase to enhance broiler feed digestibility.
AB  - This study was carried out to evaluate the effect of a multi-carbohydrase complex
      (MCC) rich in xylanase (Xyl) and arabinofuranosidase (Abf) on overall broiler
      feed digestibility in broilers. Energy utilization and digestibility of dry
      matter (DM), organic matter (OM), protein, starch, fat, and insoluble and soluble
      fibers were measured using the mass-balance method. The experiment was carried
      out on 120 broilers (3-week-old chickens). Broilers were distributed over 8
      treatments to evaluate the effect of the dietary arabinoxylan content and
      nutrient density with and without MCC (Rovabio(r) Advance). The graded content of
      arabinoxylan (AX) was obtained using different raw materials (wheat, rye, barley,
      and dried distillers' wheat). Diet-energy density was modified with added fat.
      Measurements indicated that nutrient density and AX content had a significant
      effect on most digestibility parameters. Apparent metabolizable energy (AME) was
      significantly increased (265 kcal kg-1) by MCC. The addition of MCC also resulted
      in significant improvement in the digestibility of all evaluated nutrients, with
      average improvements of 3.0, 3.3, 3.2, 3.0, 6.2, 2.9, 5.8, and 3.8% units for DM,
      OM, protein, starch, fat, insoluble and soluble fibers, and energy utilization,
      respectively. The interaction between MCC and diet composition was significant
      for the digestibility of OM, fat, protein, and energy. Nutrient digestibility and
      diet AME were negatively correlated with AX content (P < 0.001). However, the
      addition of MCC resulted in a reduction of this negative effect (P < 0.001). The
      AME of diets with and without the addition of MCC were successfully predicted by
      the diet digestible nutrient (i.e., starch, protein, fat, insoluble and soluble
      fibers) content with and without MCC (R2 = 0.87; RSD = 78 kcal kg-1). This study
      confirms that the presence of AX in wheat-based diets and wheat-based diets with
      other cereals and cereal by-products reduces nutrient digestibility in broiler
      chickens. Furthermore, the dietary addition of MCC, which is rich in Xyn and Abf,
      reduced deleterious effect of fiber and improved overall nutrient digestibility
      in broiler diets.

PMID- 28431148
TI  - Truncated ORF1 proteins can suppress LINE-1 retrotransposition in trans.
AB  - Long interspersed element 1 (L1) is an autonomous non-LTR retroelement that is
      active in mammalian genomes. Although retrotranspositionally incompetent and
      functional L1 loci are present in the same genomes, it remains unknown whether
      non-functional L1s have any trans effect on mobilization of active elements.
      Using bioinformatic analysis, we identified over a thousand of human L1 loci
      containing at least one stop codon in their ORF1 sequence. RNAseq analysis
      confirmed that many of these loci are expressed. We demonstrate that introduction
      of equivalent stop codons in the full-length human L1 sequence leads to the
      expression of truncated ORF1 proteins. When supplied in trans some truncated
      human ORF1 proteins suppress human L1 retrotransposition. This effect requires
      the N-terminus and coiled-coil domain (C-C) as mutations within the ORF1p C-C
      domain abolish the suppressive effect of truncated proteins on L1
      retrotransposition. We demonstrate that the expression levels and length of
      truncated ORF1 proteins influence their ability to suppress L1
      retrotransposition. Taken together these findings suggest that L1
      retrotransposition may be influenced by coexpression of defective L1 loci and
      that these L1 loci may reduce accumulation of de novo L1 integration events.

PMID- 28431150
TI  - The natural history of children with joint hypermobility syndrome and Ehlers
      Danlos hypermobility type: a longitudinal cohort study.
AB  - Objectives: The objective of the manuscript was to describe the natural history
      of complaints and disability in children diagnosed with joint hypermobility
      syndrome (JHS)/Ehlers-Danlos-hypermobility type (EDS-HT) and to identify the
      constructs that underlie functional decline. Methods: One hundred and one JHS/EDS
      HT children were observed over 3 years and assessed at three time points on the
      following: functional impairments, quality of life, connective tissue laxity,
      muscle function, postural control and musculoskeletal and multi-systemic
      complaints. Cluster analysis was performed to identify subgroups in severity.
      Clinical profiles were determined for these subgroups, and differences were
      assessed by multivariate analysis of covariance. Mixed linear regression models
      were used to determine the subsequent trajectories. Finally, an exploratory
      factor analysis was used to uncover the underlying constructs of functional
      impairment. Results: Three clusters of children were identified in terms of
      functional impairment: mild, moderately and severely affected. Functional
      impairment at baseline was predictive of worsening trajectories in terms of
      reduced walking distance and decreased quality of life (P ? 0.05) over 3 years.
      Multiple interactions between the secondary outcomes were observed, with four
      underlying constructs identified. All four constructs (multi-systemic effects,
      pain, fatigue and loss of postural control) contributed significantly to
      disability (P ? 0.046). Conclusion: Children diagnosed with JHS/EDS-HT who have a
      high incidence of multi-systemic complaints (particularly, orthostatic
      intolerance, urinary incontinence and diarrhoea) and poor postural control in
      addition to high levels of pain and fatigue at baseline are most likely to have a
      deteriorating trajectory of functional impairment and, accordingly, warrant
      clinical prioritization.

PMID- 28431151
TI  - Dietary choline and phospholipid supplementation enhanced docosahexaenoic acid
      enrichment in egg yolk of laying hens fed a 2% Schizochytrium powder-added diet.
AB  - The aim of this study was to evaluate the effect of dietary phospholipid
      supplementation on laying hen performance, egg quality, and the fatty acid
      profile of egg yolks from hens fed a 2% Schizochytrium powder diet. Three-hundred
      sixty 28-wk-old Hy-line W-36 laying hens were randomly allocated to one of the 5
      dietary treatments, each treatment with 6 replicates of 12 birds each. All diets
      included 2% Schizochytrium powder (docosahexaenoic acid [DHA], 137.09 mg/g). The
      control group was not supplemented with any additional phospholipids, whereas the
      other 4 experimental diets were supplemented with 1,000 mg/kg choline (CHO),
      1,000 mg/kg monoethanolamine (MEA), 1,000 mg/kg lysophosphatidylcholine (LPC), or
      500 mg/kg LPC + 500 mg/kg MEA (LPC + MEA). The experimental diets were isocaloric
      (metabolizable energy, 11.15 MJ/kg) and isonitrogenous (crude protein, 16.60%).
      The feeding trial lasted 28 days. Laying hen performance and egg quality were not
      affected (P > 0.05) by the diets used. The monounsaturated fatty acid (MUFA)
      level was reduced in the LPC group at d 28 (P < 0.01), whereas the
      polyunsaturated fatty acid (PUFA) level was increased (P < 0.05). The omega-6 (n
      6) PUFA level of the egg yolks in the LPC group had a trend to increase in
      comparison to the control (P = 0.07). The CHO and LPC groups had higher omega-3
      (n-3) PUFA and DHA levels and lower n-6/n-3 ratios than the other groups at d 28
      (P < 0.01). The DHA content in egg yolk reached a plateau after the laying hens
      consumed the experimental diets for 14 days, and higher yolk DHA contents were
      observed in the CHO and LPC groups as compared with the other groups at d 14. It
      was concluded that dietary choline supplementation for more than 14 d enhanced
      egg yolk enrichment with n-3 PUFA and DHA when laying hen diets were supplemented
      with 2% Schizochytrium powder. All the diets had no adverse effect on hen
      performance, egg quality, or egg components under the experimental condition.

PMID- 28431152
TI  - Insights into the Existence of Isomeric Plastomes in Cupressoideae
      (Cupressaceae).
AB  - The cypress family (Cupressaceae) possesses highly rearranged plastomes that lack
      a pair of large inverted repeats typically found in land plants. A few cypress
      species have been reported to contain isomeric plastomes, but whether the
      existence of isomeric plastomes is ubiquitous in the family remains to be
      investigated with a broader taxon sampling. In this study, we sequenced the
      complete plastomes of ten species in Cupressoideae, the largest cypress
      subfamily. Cupressoideae showed relatively accelerated rates of substitutions at
      both nonsynonymous and synonymous sites as compared with other subfamilies of
      Cupressaceae. Our PCR and read mapping analyses together suggested the existence
      of isomeric plastomes in eight of the ten sequenced Cupressoideae species. The
      isomeric plastomes were also detected in 176 individuals from nine wild
      populations of four Cupressoideae species. Within Calocedrus macrolepis, we
      discovered a new type of isomeric plastomes that was likely derived from
      homologous recombination mediated by an 11-bp repeat. We conclude that isomeric
      plastomes are commonly present in Cupressoideae, thereby contributing to
      increased plastomic complexity.

PMID- 28431153
TI  - Trends in Absolute and Relative Educational Inequalities in Adult Smoking Since
      the Early 2000s: The Case of Germany.
AB  - Introduction: Since the early 2000s, several tobacco control policies have been
      implemented in Germany. Current research is inconsistent about how strengthening
      tobacco control can affect social inequalities in smoking. This study examines
      whether educational inequalities in adult smoking have widened in Germany since
      2003. Methods: Data were used from four cross-sectional national health surveys
      conducted between 2003 and 2012 (n = 54,197; age = 25-69 years). Participants who
      smoked daily or occasionally were classified as smokers. The regression-based
      Slope Index of Inequality and Relative Index of Inequality (RII) were calculated
      to estimate the extent of absolute and relative educational inequalities in
      smoking, respectively. Results: In each survey year, smoking was associated with
      lower education. Overall, crude and age-standardized smoking rates declined over
      time. Stratified by education, trends of declining smoking rates were observed
      only in the high and medium education groups, whereas no statistically
      significant trend was found in the low education group. Relative educational
      inequalities in smoking increased significantly in men (2003: RII=1.74, 95%
      confidence interval 1.46 to 2.07; 2012: RII = 2.25, 95% confidence interval 1.90
      to 2.67; p-trend = .019). Absolute educational inequalities in smoking were not
      found to have changed significantly during the study period. Conclusions: In the
      course of declining smoking rates, educational inequalities in smoking persisted
      in both absolute and relative terms. In men, relative inequalities in smoking may
      even have widened within only 9 years. Tobacco control policies should not only
      be targeted at the entire population but also attempt to reduce social
      inequalities in smoking by focusing more on socially disadvantaged groups.
      Implications: Smoking is associated with lower education in most European
      countries and contributes to social inequalities in health. Since the beginning
      of the 2000s, Germany has implemented a variety of tobacco control policies to
      reduce smoking in the population. This study reveals that despite a general
      decline in adult smoking, educational inequalities in smoking have persisted and
      even widened in Germany since 2003. The findings emphasize that more targeted
      efforts are needed to tackle smoking-induced inequalities in health.

PMID- 28431154
TI  - Physiological characterization of a halotolerant anoxygenic phototrophic Fe(II)
      oxidizing green-sulfur bacterium isolated from a marine sediment.
AB  - Anoxygenic photoautotrophic bacteria which use light energy and electrons from
      Fe(II) for growth, so-called photoferrotrophs, are suggested to have been amongst
      the first phototrophic microorganisms on Earth and to have contributed to the
      deposition of sedimentary iron mineral deposits, i.e. banded iron formations. To
      date only two isolates of marine photoferrotrophic bacteria exist, both of which
      are closely related purple non-sulfur bacteria. Here we present a novel green
      sulfur photoautotrophic Fe(II) oxidizer isolated from a marine coastal sediment,
      Chlorobium sp. strain N1, which is closely related to the freshwater green-sulfur
      bacterium Chlorobium luteolum DSM273 that is incapable of Fe(II) oxidation.
      Besides Fe(II), our isolated strain grew phototrophically with other inorganic
      and organic substrates such as sulfide, hydrogen, lactate or yeast extract.
      Highest Fe(II) oxidation rates were measured at pH 7.0-7.3, the temperature
      optimum was 25 degrees C. Mossbauer spectroscopy identified ferrihydrite as the
      main Fe(III) mineral and fluorescence and helium-ion microscopy revealed cell
      mineral aggregates without obvious cell encrustation. In summary, our study
      showed that the new isolate is physiologically adapted to the conditions of its
      natural habitat but also to conditions as proposed for early Earth and is thus a
      suitable model organism for further studies addressing phototrophic Fe(II)
      oxidation on early Earth.

PMID- 28431155
TI  - Motoring through: the role of kinesin superfamily proteins in female meiosis.
AB  - BACKGROUND: The kinesin motor protein family consists of 14 distinct subclasses
      and 45 kinesin proteins in humans. A large number of these proteins, or their
      orthologues, have been shown to possess essential function(s) in both the mitotic
      and the meiotic cell cycle. Kinesins have important roles in chromosome
      separation, microtubule dynamics, spindle formation, cytokinesis and cell cycle
      progression. This article contains a review of the literature with respect to the
      role of kinesin motor proteins in female meiosis in model species. Throughout, we
      discuss the function of each class of kinesin proteins during oocyte meiosis, and
      where such data are not available their role in mitosis is considered. Finally,
      the review highlights the potential clinical importance of this family of
      proteins for human oocyte quality. OBJECTIVE AND RATIONALE: To examine the role
      of kinesin motor proteins in oocyte meiosis. SEARCH METHODS: A search was
      performed on the Pubmed database for journal articles published between January
      1970 and February 2017. Search terms included 'oocyte kinesin' and 'meiosis
      kinesin' in addition to individual kinesin names with the terms oocyte or
      meiosis. OUTCOMES: Within human cells 45 kinesin motor proteins have been
      discovered, with the role of only 13 of these proteins, or their orthologues,
      investigated in female meiosis. Furthermore, of these kinesins only half have
      been examined in mammalian oocytes, despite alterations occurring in gene
      transcripts or protein expression with maternal ageing, cryopreservation or
      behavioral conditions, such as binge drinking, for many of them. WIDER
      IMPLICATIONS: Kinesin motor proteins have distinct and important roles throughout
      oocyte meiosis in many non-mammalian model species. However, the functions these
      proteins have in mammalian meiosis, particularly in humans, are less clear owing
      to lack of research. This review brings to light the need for more experimental
      investigation of kinesin motor proteins, particularly those associated with
      maternal ageing, cryopreservation or exposure to environmental toxicants.

PMID- 28431156
TI  - A Paradigm Shift?

PMID- 28431157
TI  - Agreement between renal prescribing references and determination of prescribing
      appropriateness in hospitalized patients with chronic kidney disease.
AB  - Background: Chronic kidney disease (CKD) is a risk factor for adverse drug
      events. The clinical significance of discordance between renal prescribing
      references is unknown. Aim: We determined the prevalence of potentially
      inappropriate prescribing (PIP) in CKD, measured agreement between two
      prescribing references, and assessed potential for harm consequent to PIP.
      Design: Single-centre observational study. Methods: A random sample of
      hospitalized patients with CKD were grouped according to baseline CKD stage (3,
      4, or 5). Prescriptions requiring caution in CKD were referenced against the
      Renal Drug Handbook (RDH) and British National Formulary (BNF) to identify PIP
      (non-compliance with recommendations). Inter-reference agreement was measured
      using percentage agreement and Kappa coefficient. Potential for harm consequent
      to PIP was assessed by physicians and pharmacists using a validated scale. One
      year mortality was compared between patients with or without PIP during
      admission. Results: Among 119 patients (median age 73 years, 50% male), 136 cases
      of PIP were identified in 78 (65.5%) patients. PIP prevalence, per patient, was
      64.7% using the BNF and 28.6% using the RDH (fair agreement, Kappa 0.33, P < 
      0.001). The majority (63.2%) of PIP cases detected exclusively by the BNF carried
      minimal or no potential for harm. PIP was not significantly associated with one
      year mortality (34.7% vs. 21.1%, P = 0.14). Conclusions: PIP was common in
      hospitalized patients with CKD. Substantial discordance between renal prescribing
      references was apparent. The development of universally-adopted, evidence-based,
      prescribing guidelines for CKD might optimize medications safety in this
      vulnerable group.

PMID- 28431158
TI  - Effects of supplementation level and feeding schedule of butyrate glycerides on
      the growth performance and carcass composition of broiler chickens.
AB  - Mixed mono- and tributyrate glycerides have been used for effective delivery of
      butyrate to the gut to benefit broilers. However, limited information is
      available on the efficacy of butyrate glycerides individually and in combination
      with different levels and feeding schedules. The present study has first
      investigated the effects of monobutyrin at inclusion levels of zero, 500, 1,000,
      2,000, and 3,000 ppm on the performance of broilers, and second, the effects of
      its combination with tributyrin. In the monobutyrin trial, there were no overall
      significant differences in average daily gain or feed efficiency. However, 2,000
      ppm birds had significantly decreased abdominal fat deposition compared to
      controls (P <= 0.05), and the breast muscle deposition increased in a dose
      response manner to the supplementation of monobutyrin (P <= 0.05). The
      combination trial tested 5 treatment groups: control, 500 ppm tributyrin + 500
      ppm monobutyrin (5T5M), 500 ppm tributyrin + 500 ppm monobutyrin staggered
      (5T5Ms), 500 ppm tryibutyrin + 2,000 ppm monobutyrin (5T20M), or 500 ppm
      tributyrin + 2,000 ppm monobutyrin staggered (5T20Ms). In staggered groups, birds
      were fed tributyrin for one wk followed by 2 wk of monobutyrin, after which the
      feed was butyrate glyceride free. The non-staggered groups had constant
      inclusions levels through the 5 weeks. There were no significant differences in
      average daily gain or feed efficiency among groups. At 5 wk of age, all treatment
      groups except for 5T5Ms had significantly lower relative abdominal fat weight
      compared to control birds (P <= 0.05), although 5T5Ms birds demonstrated a trend
      for a decrease (P = 0.095). Relative breast muscle weight was significantly
      increased only in 5T5M birds over control birds at 5 wk of age (P <= 0.05). Serum
      biochemistry revealed significant changes in factors relating to muscle growth
      and fat deposition (P <= 0.05). These results indicate a consistent shift in
      lipid metabolism with the addition of butyrate glycerides and that the deposition
      of breast muscle may be highest with the incorporation of butyrate glycerides at
      a moderate level for the duration of development.

PMID- 28431159
TI  - Likelihood of Tree Topologies with Fossils and Diversification Rate Estimation.
AB  - Since the diversification process cannot be directly observed at the human scale,
      it has to be studied from the information available, namely the extant taxa and
      the fossil record. In this sense, phylogenetic trees including both extant taxa
      and fossils are the most complete representations of the diversification process
      that one can get. Such phylogenetic trees can be reconstructed from molecular and
      morphological data, to some extent. Among the temporal information of such
      phylogenetic trees, fossil ages are by far the most precisely known (divergence
      times are inferences calibrated mostly with fossils). We propose here a method to
      compute the likelihood of a phylogenetic tree with fossils in which the only
      considered time information is the fossil ages, and apply it to the estimation of
      the diversification rates from such data. Since it is required in our
      computation, we provide a method for determining the probability of a tree
      topology under the standard diversification model. Testing our approach on
      simulated data shows that the maximum likelihood rate estimates from the
      phylogenetic tree topology and the fossil dates are almost as accurate as those
      obtained by taking into account all the data, including the divergence times.
      Moreover, they are substantially more accurate than the estimates obtained only
      from the exact divergence times (without taking into account the fossil record).
      We also provide an empirical example composed of 50 Permo-Carboniferous
      eupelycosaur (early synapsid) taxa ranging in age from about 315 Ma (Late
      Carboniferous) to 270 Ma (shortly after the end of the Early Permian). Our
      analyses suggest a speciation (cladogenesis, or birth) rate of about 0.1 per
      lineage and per myr, a marginally lower extinction rate, and a considerable
      hidden paleobiodiversity of early synapsids. [Extinction rate; fossil ages;
      maximum likelihood estimation; speciation rate.].

PMID- 28431160
TI  - Progress in Ebola Virus Vaccine Development.

PMID- 28431161
TI  - Engineering a high-affinity peptide binding site into the anti-CEA mAb M5A.
AB  - We have previously identified a cyclic peptide called meditope which binds to the
      central cavity of the Fab portion of cetuximab and shown that this peptide
      binding site can be grafted, or 'meditope-enabled', onto trastuzumab. This
      peptide has been shown to act as a hitch for the non-covalent attachment of
      imaging agents to meditope-enabled antibodies. Herein, we explore the process of
      grafting this peptide binding site onto M5A, an anti-CEA antibody in clinical
      trials for cancer diagnostics. In order to explore the contributions of the amino
      acids, we sequentially introduced pairs of amino acid substitutions into the Fab
      and then we reverse-substituted key residues in the presence of the other
      substitutions. We demonstrate that Pro40Thr, Gly41Asn, Phe83Ile and Thr85Asp in
      the light chain are sufficient to recreate the meditope binding site in M5A with
      single-digit micromolar affinity. We show that Pro40 abrogates peptide binding in
      the presence of the other 12 residue substitutions, and that the presence of all
      13 substitutions does not interfere with antibody:antigen recognition.
      Collectively, these studies provide detailed insight for defining and fine-tuning
      the binding affinity of the meditope binding site within an antibody.

PMID- 28431162
TI  - Risk of serious bacterial infection associated with tumour necrosis factor-alpha
      inhibitors in children with juvenile idiopathic arthritis.
AB  - Objectives: TNF-alpha inhibitors (TNFIs) have a black box warning for increased
      risk of serious infection that was based on evidence from studies of adults.
      Evidence of the association is lacking for children. We aimed to examine the risk
      of infection posed by TNFIs compared with DMARDs in children with JIA. Methods:
      We conducted a cohort study using the 2009-13 Truven MarketScan Commercial Claims
      and Encounters database. Children <16 years old with JIA who initiated
      monotherapy with TNFIs or DMARDs were identified and followed for occurrence of
      serious bacterial infection requiring hospitalization. Cox proportional hazard
      models were used to estimate hazard ratios for infection associated with TNFIs
      compared with DMARDs, adjusting for potential confounders with high-dimensional
      propensity scores and time-varying CS use. Results: We identified 2013 DMARD
      initiators and 482 TNFI initiators with a mean follow-up of 255 and 307 days,
      respectively. We identified 18 and 11 patients with a serious infection in the
      DMARD and TNFI groups, resulting in crude rates of 1.28 (95% CI 0.76-2.02) and
      2.72 (95%CI 1.36-4.86) per 100 person-years, respectively. In adjusted models,
      TNFIs were associated with an increased risk of serious bacterial infection
      compared with DMARDs (adjusted hazard ratio 2.72, 95% CI: 1.08, 6.86).
      Conclusion: Use of TNFIs poses a higher risk of serious infection compared with
      DMARDs in children with JIA. Our analysis confirms the US Food and Drug
      Administration warning about TNFI-associated infection in children with JIA.

PMID- 28431163
TI  - An Evaluation of the Human Relevance of the Lung Tumors Observed in Female Mice
      Treated With Permethrin Based on Mode of Action.
AB  - Permethrin increased the incidence of bronchiolo-alveolar adenomas in female mice
      but not male mice or female or male rats. Studies were conducted to determine
      whether permethrin has mitogenic activity in Club cells in mouse lung as the
      basis for the mode of action (MOA) for the lung adenoma induction. Several short
      term experiments focusing on time-course, dose-response, reversibility, sex
      difference, strain difference, and species difference were evaluated for Club
      cell proliferation and morphology. The findings demonstrated that permethrin
      slightly and continuously enhanced Club cell proliferation at tumor-associated
      dose levels in female mice, but did not increase proliferation in male mice or in
      female rats. Electron microscopic examination demonstrated that permethrin
      produced morphological alterations in Club cells prior to increasing the Club
      cell proliferation. There was no evidence of increased cell death. These
      alterations in Club cells were also observed with a close structural analog
      cypermethrin. Taken together, the present studies provide evidence that the MOA
      for induction of mouse lung adenomas by permethrin involves slight morphological
      effects on Club cells, sustained Club cell proliferation, and eventually
      hyperplasia and bronchiolo-alveolar adenoma in susceptible mice. The potential
      human carcinogenic hazard of permethrin based on the tumorigenic MOA for lung
      tumors in mice was evaluated using the International Programme on Chemical Safety
      Human Relevance Framework. As humans are quantitatively much less sensitive to
      agents that increase Club cell proliferation and tumor formation in mice, it is
      not likely permethrin will lead to an increase in susceptibility to lung tumor
      development in humans. Epidemiological data for permethrin strongly supports this
      conclusion.

PMID- 28431165
TI  - Corrigendum to: "Glial fibrillary acidic protein plasma levels are correlated
      with degree of hypothermia during cardiopulmonary bypass in congenital heart
      disease surgery" [Interact CardioVasc Thorac Surg 2017].

PMID- 28431166
TI  - Landscape Genetics of Aedes mcintoshi (Diptera: Culicidae), an Important Vector
      of Rift Valley Fever Virus in Northeastern Kenya.
AB  - Rift Valley fever virus (RVFV) is a vector-borne, zoonotic disease that affects
      humans, wild ungulates, and domesticated livestock in Africa and the Arabian
      Peninsula. Rift Valley fever virus exhibits interepizootic and epizootic phases,
      the latter defined by widespread virus occurrence in domesticated livestock.
      Kenya appears to be particularly vulnerable to epizootics, with 11 outbreaks
      occurring between 1951 and 2007. The mosquito species Aedes mcintoshi (subgenus
      Neomelaniconion) is an important primary vector for RVFV in Kenya. Here, we
      investigate associations between genetic diversity and differentiation of one
      regional subclade of Ae. mcintoshi in Northeastern Kenya with environmental
      variables, using a multivariate statistical approach. Using CO1 (cytochrome
      oxidase subunit 1) sequence data deposited in GenBank, we found no evidence of
      isolation by distance contributing to genetic differentiation across the study
      area. However, we did find significant CO1 subpopulation structure and
      associations with recent mean precipitation values. In addition, variation in
      genetic diversity across our seven sample sites was associated with both
      precipitation and percentage clay in the soil. The large number of haplotypes
      found in this data set indicates that a great deal of diversity remains unsampled
      in this region. Additional sampling across a larger geographic area, combined
      with next-generation sequencing approaches that better characterize the genome,
      would provide a more robust assessment of genetic diversity and differentiation.
      Further understanding of the genetic structure of Ae. mcintoshi could provide
      useful information regarding the potential for RVFV to spread across East African
      landscapes.

PMID- 28431164
TI  - Low Activity Microstates During Sleep.
AB  - Study Objectives: To better understand the distinct activity patterns of the
      brain during sleep, we observed and investigated periods of diminished
      oscillatory and population spiking activity lasting for seconds during non-rapid
      eye movement (non-REM) sleep, which we call "LOW" activity sleep. Methods: We
      analyzed spiking and local field potential (LFP) activity of hippocampal CA1
      region alongside neocortical electroencephalogram (EEG) and electromyogram (EMG)
      in 19 sessions from four male Long-Evans rats (260-360 g) during natural
      wake/sleep across the 24-hr cycle as well as data from other brain regions
      obtained from http://crcns.org.1,2. Results: LOW states lasted longer than
      OFF/DOWN states and were distinguished by a subset of "LOW-active" cells. LOW
      activity sleep was preceded and followed by increased sharp-wave ripple activity.
      We also observed decreased slow-wave activity and sleep spindles in the
      hippocampal LFP and neocortical EEG upon LOW onset, with a partial rebound
      immediately after LOW. LOW states demonstrated activity patterns consistent with
      sleep but frequently transitioned into microarousals and showed EMG and LFP
      differences from small-amplitude irregular activity during quiet waking. Their
      likelihood decreased within individual non-REM epochs yet increased over the
      course of sleep. By analyzing data from the entorhinal cortex of rats,1 as well
      as the hippocampus, the medial prefrontal cortex, the postsubiculum, and the
      anterior thalamus of mice,2 obtained from http://crcns.org, we confirmed that LOW
      states corresponded to markedly diminished activity simultaneously in all of
      these regions. Conclusions: We propose that LOW states are an important
      microstate within non-REM sleep that provide respite from high-activity sleep and
      may serve a restorative function.

PMID- 28431167
TI  - Performance of 18F-FDG PET/CT in the Characterization of Adrenal Masses in
      Noncancer Patients: A Prospective Study.
AB  - Context: Few prospective studies have evaluated the role of 18F
      fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
      PET/CT) in the characterization of adrenal masses. Objective: To assess the
      performance of 18F-FDG PET/CT in the malignancy diagnosis of adrenal masses in
      noncancer patients. Design: Prospective multicenter study. Material and Methods:
      The study population consisted of 87 patients (87 adrenal masses) referred to
      endocrine surgeons: 56 with mass diameter >=40 mm and 31 with a diameter <40 mm
      and of indeterminate nature based on unenhanced and washout CT attenuation
      densities. Fourteen patients had hypercortisolism. Adrenal masses were
      characterized by 18F-FDG PET/CT. Histology was the gold standard for the
      diagnosis of malignancy. In the absence of pathological proof (n = 23), the
      nature of the lesion was based on the 12-month imaging follow-up. Results:
      Fifteen adrenal masses were classified as malignant (including 11 adrenocortical
      carcinomas) and 72 as benign. Compared with benign lesions, malignant lesions
      were larger in size (P = 0.003), had higher unenhanced densities (P = 0.002),
      lower relative washout values (P = 0.007), and higher 18F-FDG uptake parameters
      (P < 10-3). The optimal threshold value of (Tumor SUVmax:Liver SUVmax) the ratio
      for malignancy was >1.5 with sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy of 86.7%, 86.1%, 56.5%, 96.9%, and 86.2%,
      respectively. Conclusions: Our results show that 18F-FDG PET/CT complements
      adrenal washout CT in the evaluation of adrenal masses and should be recommended
      in the evaluation of large and/or indeterminate adrenal masses.

PMID- 28431169
TI  - SPA-LN: a scoring function of ligand-nucleic acid interactions via optimizing
      both specificity and affinity.
AB  - Nucleic acids have been widely recognized as potential targets in drug discovery
      and aptamer selection. Quantifying the interactions between small molecules and
      nucleic acids is critical to discover lead compounds and design novel aptamers.
      Scoring function is normally employed to quantify the interactions in structure
      based virtual screening. However, the predictive power of nucleic acid-ligand
      scoring functions is still a challenge compared to other types of biomolecular
      recognition. With the rapid growth of experimentally determined nucleic acid
      ligand complex structures, in this work, we develop a knowledge-based scoring
      function of nucleic acid-ligand interactions, namely SPA-LN. SPA-LN is optimized
      by maximizing both the affinity and specificity of native complex structures. The
      development strategy is different from those of previous nucleic acid-ligand
      scoring functions which focus on the affinity only in the optimization. The
      native conformation is stabilized while non-native conformations are destabilized
      by our optimization, making the funnel-like binding energy landscape more biased
      toward the native state. The performance of SPA-LN validates the development
      strategy and provides a relatively more accurate way to score the nucleic acid
      ligand interactions.

PMID- 28431170
TI  - Early Total Enteral Feeding in Stable Very Low Birth Weight Infants: A Before and
      After Study.
AB  - Background: Fear of necrotizing enterocolitis (NEC) has perpetuated delayed
      initiation and slow advancement of enteral feeding in very low birth weight
      (VLBW) infants with inherent risks of parenteral alimentation. The objective of
      this study was to assess effect of early total enteral feeding (ETEF) on day of
      achievement of full enteral feeds, feed intolerance, NEC and sepsis. Methods: In
      total, 208 stable VLBW neonates (28-34 weeks) admitted during 6 month periods of
      three consecutive years were enrolled. First phase (n = 73) constituted the
      'before' phase with standard practice of initial intravenous fluid therapy and
      slow enteral feeding. The second prospective phase (n = 51) consisted of
      implementation of ETEF with infants receiving full enteral feeds as per day's
      fluid requirement since Day 1 of life. The third phase (n = 84) was chosen to
      assess the sustainability of change in practice. Results: Day of achievement of
      full feeds was significantly earlier in Phases 2 and 3 compared with Phase 1
      (8.97 and 5.47 vs. 14.44 days, respectively, p = 0.0001). Incidence of feed
      intolerance was comparable between Phases 1 and 2 (22 vs. 14%, p = 0.28), with
      marked reduction in incidence of NEC (14 vs. 4%, p = 0.028). There was a
      significant decrease in sepsis, duration of parenteral fluid and antibiotic
      therapy as well as hospital stay with comparable mortality. Conclusion: In stable
      preterm VLBW infants, ETEF is safe and has the benefit of optimizing nutrition
      with decrease in sepsis, NEC and hospital stay.

PMID- 28431168
TI  - Identifying new susceptibility genes on dopaminergic and serotonergic pathways
      for the framing effect in decision-making.
AB  - The framing effect refers the tendency to be risk-averse when options are
      presented positively but be risk-seeking when the same options are presented
      negatively during decision-making. This effect has been found to be modulated by
      the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene
      (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and
      which are associated with affective processing. The current study aimed to
      identify new genetic variations of genes on dopaminergic and serotonergic
      pathways that may contribute to individual differences in the susceptibility to
      framing. Using genome-wide association data and the gene-based principal
      components regression method, we examined genetic variations of 26 genes on the
      pathways in 1317 Chinese Han participants. Consistent with previous studies, we
      found that the genetic variations of the SLC6A4 gene and the COMT gene were
      associated with the framing effect. More importantly, we demonstrated that the
      genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which
      is involved in the synthesis of both dopamine and serotonin, contributed to
      individual differences in the susceptibility to framing. Our findings shed light
      on the understanding of the genetic basis of affective decision-making.

PMID- 28431172
TI  - Quantitative analysis of Li distributions in battery material Li1-xFePO4 using Fe
      M2,3-edge and valence electron energy loss spectra.
AB  - The spatial distribution of Li ions in a lithium iron phosphate (Li1-xFePO4)
      single crystal after chemical delithiation is quantitatively investigated using
      Fe M2,3-edge and valence electron energy loss (EEL) spectroscopy techniques. Li
      contents between those of end-member compositions LiFePO4 and FePO4 are found to
      correspond to reproducible changes in Fe M2,3-edge and valence EEL spectra across
      an interface between LiFePO4 and FePO4 regions. Quantitative analysis of these
      changes is used to estimate the local valence states of Fe ions, from which the
      Li concentration in the intermediate phase can be deduced. The faster recording
      time for valence EEL spectra than Fe M2,3-edge spectra makes measurement of the
      former a more efficient and reproducible means of estimating Li distributions.

PMID- 28431171
TI  - Heritability of Heart Rate Response to Arousals in Twins.
AB  - Objectives: To determine if the large and highly reproducible interindividual
      differences in arousal intensity and heart rate response to arousal (DeltaHR)
      during non-REM sleep are heritable. Methods: Polysomnograms of 55 monozygotic (14
      male and 41 female pairs) and 36 dizygotic (15 male and 21 female pairs) same-sex
      twin pairs were analyzed. Arousals were scored using the 2012 American Academy of
      Sleep Medicine criteria. Arousal intensity was scaled (between 0 and 9) using an
      automatic algorithm based on the change in electroencephalogram time and
      frequency characteristics. The DeltaHR was determined at each arousal. We
      calculated average arousal duration, average arousal intensity, average overall
      DeltaHR, average DeltaHR at a given arousal intensity, slope of DeltaHR per
      arousal intensity, and arousal intensity threshold of DeltaHR. Results: The
      intraclass correlations among monozygotic and dizygotic twin pairs were 0.663 and
      0.146, respectively, for average arousal intensity, and 0.449 and 0,
      respectively, for arousal intensity threshold of DeltaHR controlling for age,
      sex, and race. These values imply large broad sense heritability (H2) for these
      traits. This evidence was confirmed by a robust maximum likelihood-based variance
      components estimation approach, with an additive genetic heritability of 0.64
      (95% confidence interval: 0.48 to 0.80) for average arousal intensity and a
      combined additive and dominance genetic heritability and of 0.46 (0.25 to 0.68)
      for arousal intensity threshold of DeltaHR. Results also suggested significant
      additive genetic effects for average arousal duration, DeltaHR at arousal
      intensity scale 4 and the overall average DeltaHR. Conclusion: Genetic factors
      explain a significant fraction of the phenotypic variability for average arousal
      intensity and arousal intensity threshold of DeltaHR. Results suggest that the
      duration of arousals and specific average DeltaHR values may also be heritable
      traits. Clinical trial registration: NCT02827461.

PMID- 28431173
TI  - Programmatic access to bioinformatics tools from EMBL-EBI update: 2017.
AB  - Since 2009 the EMBL-EBI provides free and unrestricted access to several
      bioinformatics tools via the user's browser as well as programmatically via Web
      Services APIs. Programmatic access to these tools, which is fundamental to
      bioinformatics, is increasingly important as more high-throughput data is
      generated, e.g. from proteomics and metagenomic experiments. Access is available
      using both the SOAP and RESTful approaches and their usage is reviewed regularly
      in order to ensure that the best, supported tools are available to all users. We
      present here an update describing the latest enhancement to the Job Dispatcher
      APIs as well as the governance under it.

PMID- 28431174
TI  - Opportunities for exercise during pullet rearing, Part II: Long-term effects on
      bone characteristics of adult laying hens at the end-of-lay.
AB  - Osteoporosis in laying hens has been a production and welfare concern for several
      decades. The objective of this study was to determine whether differing
      opportunities for exercise during pullet rearing influences long-term bone
      quality characteristics in end-of-lay hens. A secondary objective was to assess
      whether differing opportunities for exercise in adult housing systems alters bone
      quality characteristics in end-of-lay hens. Four flock replicates of 588 Lohmann
      Selected Leghorn-Lite pullets were reared in either conventional cages (Conv) or
      an aviary rearing system (Avi) and placed into conventional cages (CC), 30-bird
      furnished cages (FC-S), or 60-bird furnished cages (FC-L) for adult housing. Wing
      and leg bones were collected at the end-of-lay to quantify bone composition and
      strength using quantitative computed tomography and bone breaking strength (BBS).
      At the end-of-lay, Avi hens had greater total and cortical cross-sectional area
      (P < 0.05) for the radius and tibia, greater total bone mineral content of the
      radius (P < 0.001), and greater tibial cortical bone mineral content (P = 0.029)
      than the Conv hens; however, total bone mineral density of the radius (P < 0.001)
      and cortical bone mineral density of the radius and tibia (P < 0.001) were
      greater in the Conv hens. Hens in the FC-L had greater total bone mineral density
      for the radius and tibia (P < 0.05) and greater trabecular bone mineral density
      for the radius (P = 0.027), compared to hens in the FC-S and CC. Total bone
      mineral content of the tibia (P = 0.030) and cortical bone mineral content of the
      radius (P = 0.030) and tibia (P = 0.013) were greater in the FC-L compared to the
      CC. The humerus of Conv hens had greater BBS than the Avi hens (P < 0.001), and
      the tibiae of FC-L and FC-S hens had greater BBS than CC hens (P = 0.006).
      Increased opportunities for exercise offered by the aviary rearing system
      provided improved bone quality characteristics lasting through to the end-of-lay.

PMID- 28431175
TI  - minepath.org: a free interactive pathway analysis web server.
AB  - Minepath: ( www.minepath.org ) is a web-based platform that elaborates on, and
      radically extends the identification of differentially expressed sub-paths in
      molecular pathways. Besides the network topology, the underlying MinePath
      algorithmic processes exploit exact gene-gene molecular relationships (e.g.
      activation, inhibition) and are able to identify differentially expressed pathway
      parts. Each pathway is decomposed into all its constituent sub-paths, which in
      turn are matched with corresponding gene expression profiles. The highly ranked,
      and phenotype inclined sub-paths are kept. Apart from the pathway analysis
      algorithm, the fundamental innovation of the MinePath web-server concerns its
      advanced visualization and interactive capabilities. To our knowledge, this is
      the first pathway analysis server that introduces and offers visualization of the
      underlying and active pathway regulatory mechanisms instead of genes. Other
      features include live interaction, immediate visualization of functional sub
      paths per phenotype and dynamic linked annotations for the engaged genes and
      molecular relations. The user can download not only the results but also the
      corresponding web viewer framework of the performed analysis. This feature
      provides the flexibility to immediately publish results without publishing
      source/expression data, and get all the functionality of a web based pathway
      analysis viewer.

PMID- 28431176
TI  - Effect of melatonin on renewal of chicken small intestinal mucosa.
AB  - A higher concentration of melatonin (MEL) in the intestine - even more than that
      in the plasma and pineal gland - implies its putative important role in the
      gastrointestinal structural or functional regulation. However, little evidence
      has shown that MEL can regulate the physiological functions of the intestinal
      mucosa. In this study, fertilized chicken eggs were treated with MEL (0.1 to 10
      MUg/d) from embryonic d 12 (E12) to post-hatching d 6 (D6), and the small
      intestine samples were collected at D6 to determine the changes in mucosal
      construction and function. Results of HE staining showed that the enterocyte
      number was not changed after MEL treatment. Alcian blue - periodic acid Schiff
      reaction (AB-PAS) staining and qRT-PCR showed that the goblet cells populations
      and mucins gene (MUC2) expression in the small intestine were significantly
      increased after MEL treatment. Meanwhile, 5-ethynyl-2'-deoxyuridine staining
      showed that both the proliferation and migration rates of the small intestine
      mucosal epithelium were promoted by MEL treatment. Importantly, MEL significantly
      increased the activities of the digestive enzymes (maltase, sucrose, and lactase)
      and expression of the nutrient transporter genes such as GLUT5, BOAT, and EAAT3
      mRNAs in the duodenum or jejunum. Meanwhile, the expression of Notch receptors
      (Notch1 and Notch2) and their ligands (Dll1 and Dll4) were remarkably decreased
      after MEL treatment. In conclusion, MEL treatment increased the goblet cell
      populations, MUC2 expression, epithelium migration, and digestive and absorptive
      function of the chicken small intestine involving repressed Notch signaling.

PMID- 28431177
TI  - Altered Functional Connectivity in Idiopathic Rapid Eye Movement Sleep Behavior
      Disorder: A Resting-State EEG Study.
AB  - Study Objectives: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is
      considered as a prodromal stage of synucleinopathy. Although loss of functional
      connectivity is implicated in neurodegenerative diseases, network characteristics
      of electroencephalography (EEG) in iRBD are unknown. Therefore, we evaluated
      resting-state EEG functional connectivity to identify the brain network changes
      in patients with iRBD. Methods: We prospectively enrolled 20 patients with
      polysomnography-confirmed iRBD and 16 controls. Four patients with mild cognitive
      impairment were excluded from the analysis after cognitive function tests. EEG
      was recorded during relaxed wakefulness. We computed the weighted phase lag index
      as a measure of functional connectivity from EEG recordings. Results: All
      patients with iRBD (mean age 64.3 years; men, 68.8%) had no overt manifestations
      of neurodegenerative diseases such as Parkinsonism or dementia. The mean duration
      from symptom onset was 4.8 years. Overall connectivity strength did not differ
      between the two groups in all frequency bands. However, comparisons of each
      functional connection with the nonparametric permutation test demonstrated iRBD
      had decreased delta-band functional connectivity in the frontal regions. There
      were no significantly increased functional connections in all frequencies. The
      altered connections had a significant correlation with RBD questionnaire scores.
      Notably, delta-band weighted phase lag index between left frontal and central
      regions was correlated with verbal fluency performance (r = 0.486, p = .007).
      Conclusions: Resting-state brain network of iRBD was characterized by a loss of
      delta-band functional connectivity. Therefore, functional networks in iRBD are
      altered at the early phase of disease.

PMID- 28431178
TI  - Influence of dietary calcium concentrations and the calcium-to-non-phytate
      phosphorus ratio on growth performance, bone characteristics, and digestibility
      in broilers.
AB  - Two experiments were conducted to determine the influence of dietary Ca
      concentrations (Experiment 1) and a combination of dietary Ca and non-phytate
      phosphorus (NPP) to create distinct Ca-to-NPP ratios (Experiment 2) in corn
      soybean meal diets fed to broiler chickens from 2 to 23 d of age. In Experiment
      1, dietary treatments consisted of 7 concentrations of Ca (0.4, 0.6, 0.8, 1.0,
      1.2, 1.4, or 1.6% of the diet; 7 treatments total), and NPP concentrations were
      maintained at 0.3%. Increasing the dietary Ca concentration while maintaining
      0.3% NPP elicited linear reductions (P < 0.01) in overall growth performance and
      tibia ash. Dietary effects also were observed for apparent retention of P and Ca,
      which decreased (P < 0.05) linearly or quadratically for birds receiving dietary
      treatments with Ca concentrations greater than 0.6%. In Experiment 2, diets were
      formulated to contain 3 concentrations of Ca (0.4, 1.0, or 1.6% of the diet) with
      NPP concentrations either constant at 0.45% or adjusted to maintain a dietary Ca
      to-NPP ratio of 2:1 (6 treatments total). Growth performance was not influenced
      by Ca concentration or the Ca-to-NPP ratio. Tibia break force was lower (P <
      0.01) in birds fed diets containing 0.4% Ca, regardless of the NPP concentration.
      Tibia ash increased (P < 0.01) as the dietary Ca concentration increased. Neither
      the dietary Ca nor NPP concentrations affected nitrogen retention (P > 0.05).
      Upon maintaining a constant 2:1 Ca-to-NPP ratio, P and Ca retention decreased (P
      < 0.01) at the highest Ca concentration. In conclusion, imbalanced Ca and NPP
      adversely influenced growth performance and nutrient retention of broilers,
      indicating the concentrations of Ca and NPP required to maximize bone structure
      and function may be higher than those required for performance.

PMID- 28431179
TI  - miRNA Regulation in Gliomas: Usual Suspects in Glial Tumorigenesis and Evolving
      Clinical Applications.
AB  - In recent years, an increasing role for noncoding small RNAs (miRNA) has been
      uncovered in carcinogenesis. These oligonucleotides can promote degradation
      and/or inhibit translation of key mRNAs. Recent studies have also highlighted a
      possible role for miRNAs in adult and pediatric brain tumors, including high- and
      low-grade gliomas, medulloblastoma, ependymoma, and neoplasms associated with
      neurofibromatosis type 1. Gliomas represent the most common category of primary
      intraparenchymal brain tumors, and, for example, manipulation of signaling
      pathways, through inhibition of PTEN transcription appears to be an important
      function of miRNA dysregulation through miR-21, miR-106b, and miR-26a. Moreover,
      altered miRNA expression in gliomas play roles in the regulation of common
      tumorigenic processes, including receptor tyrosine kinase signaling,
      angiogenesis, invasion, suppression of differentiation, cell cycle enhancement,
      and inhibition of apoptosis. Suppression of differentiation requires the
      downregulation of a number of miRNAs that are both enriched in the brain and
      required for terminal glial differentiation, including miR-219 and miR-338. Our
      evolving understanding about the biology of gliomas make them attractive for
      miRNA study, given that recent evidence suggests that epigenetic and subtle
      genetic changes may contribute to their pathogenesis. Identification of key
      miRNAs also provides a rationale for developing robust biomarkers and inhibitory
      RNA strategies for therapeutic purposes in glioma patients.

PMID- 28431180
TI  - Collagenosis of the Deep Medullary Veins: An Underrecognized Pathologic Correlate
      of White Matter Hyperintensities and Periventricular Infarction?
AB  - White matter hyperintensities (WMH) are prevalent. Although arteriolar disease
      has been implicated in their pathogenesis, venous pathology warrants
      consideration. We investigated relationships of WMH with histologic venous,
      arteriolar and white matter abnormalities and correlated findings with premortem
      neuroimaging. Three regions of periventricular white matter were sampled from
      archived autopsy brains of 24 pathologically confirmed Alzheimer disease (AD) and
      18 age-matched nonAD patients. Using trichrome staining, venous collagenosis (VC)
      of periventricular veins (<150 um in diameter) was scored for severity of wall
      thickening and occlusion; percent stenosis by collagenosis of large caliber (>200
      um) veins (laVS) was measured. Correlations were made between WMH in premortem
      neuroimaging and vascular and white matter pathology. We found greater VC (U(114)
      = 2092.5, p = 0.005 and U(114) = 2121.5, p = 0.002 for small and medium caliber
      veins, respectively) and greater laVS (t(110) = 3.46, p = 0.001) in patients with
      higher WMH scores; WMH scores correlated with VC (rs(114) = 0.27, p = 0.004) and
      laVS (rs(110) = 0.38, p < 0.001). By multiple linear regression analysis, the
      strongest predictor of WMH score was laVS (beta = 0.338, p < 0.0001). VC was
      frequent in patients with periventricular infarcts identified on imaging. We
      conclude that periventricular VC is associated with WMH in both AD and nonAD
      patients and the potential roles of VC in WMH pathogenesis merit further study.

PMID- 28431181
TI  - Protective Effect of Mesenchymal Stem Cells Against the Development of
      Intracranial Aneurysm Rupture in Mice.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stem or stromal cells
      found in multiple tissues. Intravenous MSC injections have been used to treat
      various diseases with an inflammatory component in animals and humans.
      Inflammation is emerging as a key component of pathophysiology of intracranial
      aneurysms. Modulation of inflammation by MSCs may affect sustained inflammatory
      processes that lead to aneurysmal rupture. OBJECTIVE: To assess the effect of
      MSCs on the development of aneurysm rupture using a mouse model. METHODS:
      Intracranial aneurysms were induced with a combination of a single elastase
      injection into the cerebrospinal fluid and deoxycorticosterone acetate salt
      induced hypertension in mice. We administered allogeneic bone marrow-derived MSCs
      or vehicle, 6 and 9 d after aneurysm induction. RESULTS: MSC administration
      significantly reduced rupture rate (vehicle control vs MSCs, 90% vs 36%; P <
      .05). In cell culture experiments with an MSC and mast cell coculture, MSCs
      stabilized mast cells through cyclooxygenase-2 (COX-2)-dependent production of
      prostaglandin E2, thereby reducing the release of proinflammatory cytokines from
      mast cells. Pretreatment of MSCs with COX-2 inhibitor, NS-398, abolished the
      protective effect of MSCs against the development of aneurysm rupture.
      CONCLUSION: Intravenous administration of MSCs after aneurysm formation prevented
      aneurysmal rupture in mice. The protective effect of MSCs against the development
      of aneurysm rupture appears to be mediated in part by the stabilization of mast
      cells by MSCs.

PMID- 28431182
TI  - Joint positions matter for ultrasound examination of RA patients-increased power
      Doppler signal in neutral versus flat position of hands.
AB  - Objective: Position of joints might influence the result of US examination in
      patients with RA. The purpose of this work was to compare grey-scale (GS) and
      power Doppler (PWD) findings obtained in neutral vs flat position of hands.
      Methods: A cross-sectional study of 42 RA patients with active disease. Two
      dimensional and 3D sonography of wrists and MCP joints were conducted in two
      different joint positions: neutral position, which is a slight flexion of the
      fingers with relaxed extensor muscles; and flat position, where all palm and
      volar sides of fingers touch the Table. Two dimensional GS synovitis (GSS) and
      PWD signals were scored semi-quantitatively (0-3). For 3D sonography, the
      percentage of PWD voxels within a region of interest was calculated. GSS was not
      quantified using 3D sonography. Results: Compared with neutral position, 2D PWD
      signals disappeared in 28.3% of joints upon flattening. The median global 2D PWD
      score (sum of all PWD scores of an individual patient) decreased from 8 to 3 ( P
      < 0.001), and the global 3D PWD voxel score from 3.8 to 0.9 ( P < 0.001). The
      reduction of PWD scores was similar in all joints (2D: minus 50%, 3D: minus 66.4
      80.1%). Inter- and intrareader agreement of PWD results was good (intraclass
      correlation coefficient: 0.75-0.82). Conclusion: In RA, a neutral position of the
      hands is linked to a higher sensitivity of 2D and 3D sonography in detecting PWD
      signals at wrists and MCP joints, compared with a flat position. Standardization
      of the scanning procedure is essential for obtaining comparable US results in RA
      patients in trials and clinical routines.

PMID- 28431183
TI  - Efficacy of tiamulin alone or in combination with chlortetracycline against
      experimental Mycoplasma gallisepticum infection in chickens.
AB  - Mycoplasma gallisepticum (M. gallisepticum) remains one of the most important
      diseases in poultry production. Controlling the impact of the disease is done by
      eradication of positive breeder flocks or by vaccination and medication. A widely
      used molecule in medication programs is tiamulin, a pleuromutilin antibiotic.
      Since recent data on the in vivo efficacy of this molecule are scarce, 2
      challenge studies were conducted using a recently isolated M. gallisepticum
      strain belonging to the wildtype population with regard to its tiamulin and
      tetracycline minimum inhibitory concentration (MIC). In the first challenge
      study, the dose rate of tiamulin was tested. For this, broilers were infected
      with M. gallisepticum and treated with 10 mg or 25 mg tiamulin hydrogen fumarate
      (hf)/kg body weight (BW) for 5 successive days. In a second challenge study, the
      dose rate of tiamulin combined with chlortetracycline was tested. For this,
      broilers were infected with M. gallisepticum and treated with 6.25 mg tiamulin
      hf/18.75 mg chlortetracycline hydrochloride (hcl)/kg BW or 12.5 mg tiamulin
      hf/37.5 mg chlortetracycline hcl/kg BW for 5 successive days. Clinical scoring of
      respiratory signs, macroscopic scoring of respiratory tract lesions, M.
      gallisepticum isolation from the respiratory organs, weight gain, and mortality
      were the monitored efficacy parameters. The first study demonstrated that a 5-day
      10 mg/kg BW tiamulin hf treatment provided significant protection against the M.
      gallisepticum infection. However, since the 5-day 25 mg/kg BW group was
      significantly better than the 10 mg/kg BW for reducing the post-treatment
      clinical signs and the M. gallisepticum numbers in the respiratory organs, the 25
      mg/kg BW treatment is recommended for clinical M. gallisepticum infections. In
      the second study, the combined 12.5 mg tiamulin hf/37.5 mg chlortetracycline
      hcl/kg BW resulted in a significant reduction of the severity of clinical
      respiratory disease post treatment and a significant reduction of the M.
      gallisepticum numbers in the respiratory tract.

PMID- 28431185
TI  - The effect of interspecific variation in photosynthetic plasticity on 4-year
      growth rate and 8-year survival of understorey tree seedlings in response to gap
      formations in a cool-temperate deciduous forest.
AB  - Gap formation increases the light intensity in the forest understorey. The growth
      responses of seedlings to the increase in light availability show interspecific
      variation, which is considered to promote biodiversity in forests. At the leaf
      level, some species increase their photosynthetic capacity in response to gap
      formation, whereas others do not. Here we address the question of whether the
      interspecific difference in the photosynthetic response results in the
      interspecific variation in the growth response. If so, the interspecific
      difference in photosynthetic response would also contribute to species
      coexistence in forests. We also address the further relevant question of why some
      species do not increase their photosynthetic capacity. We assumed that some cost
      of photosynthetic plasticity may constrain acquisition of the plasticity in some
      species, and hypothesized that species with larger photosynthetic plasticity
      exhibit better growth after gap formation and lower survivorship in the shade
      understorey of a cool-temperate deciduous forest. We created gaps by felling
      canopy trees and studied the relationship between the photosynthetic response and
      the subsequent growth rate of seedlings. Naturally growing seedlings of six
      deciduous woody species were used and their mortality was examined for 8 years.
      The light-saturated rate of photosynthesis (Pmax) and the relative growth rate
      (RGR) of the seedlings of all study species increased at gap plots. The extent of
      these increases varied among the species. The stimulation of RGR over 4 years
      after gap formation was strongly correlated with change in photosynthetic
      capacity of newly expanded leaves. The increase in RGR and Pmax correlated with
      the 8-year mortality at control plots. These results suggest a trade-off between
      photosynthetic plasticity and the understorey shade tolerance. Gap-demanding
      species may acquire photosynthetic plasticity, sacrificing shade tolerances,
      whereas gap-independent species may acquire shade tolerances, sacrificing
      photosynthetic plasticity. This strategic difference among species would
      contribute to species coexistence in cool-temperate deciduous forests.

PMID- 28431184
TI  - Editor's Highlight: Congener-Specific Disposition of Chiral Polychlorinated
      Biphenyls in Lactating Mice and Their Offspring: Implications for PCB
      Developmental Neurotoxicity.
AB  - Chiral polychlorinated biphenyl (PCB) congeners have been implicated by
      laboratory and epidemiological studies in PCB developmental neurotoxicity. These
      congeners are metabolized by cytochrome P450 (P450) enzymes to potentially
      neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the
      enantioselective disposition and toxicity of 2 environmentally relevant,
      neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their
      offspring following dietary exposure of the dam. Female C57BL/6N mice (8-weeks
      old) were fed daily, beginning 2 weeks prior to conception and continuing
      throughout gestation and lactation, with 3.1 umol/kg bw/d of racemic 2,2',3,5',6
      pentachlorobiphenyl (PCB 95) or 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in
      peanut butter; controls received vehicle (peanut oil) in peanut butter. PCB 95
      levels were higher than PCB 136 levels in both dams and pups, consistent with the
      more rapid metabolism of PCB 136 compared with PCB 95. In pups and dams, both
      congeners were enriched for the enantiomer eluting second on enantioselective gas
      chromatography columns. OH-PCB profiles in lactating mice and their offspring
      were complex and varied according to congener, tissue and age. Developmental
      exposure to PCB 95 versus PCB 136 differentially affected the expression of P450
      enzymes as well as neural plasticity (arc and ppp1r9b) and thyroid hormone
      responsive genes (nrgn and mbp). The results suggest that the enantioselective
      metabolism of PCBs to OH-PCBs may influence neurotoxic outcomes following
      developmental exposures, a hypothesis that warrants further investigation.

PMID- 28431186
TI  - Unfractionated heparin versus low molecular weight heparins for avoiding heparin
      induced thrombocytopenia in postoperative patients.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction
      presenting as a prothrombotic disorder related to antibody-mediated platelet
      activation. It is a paradoxical immune reaction resulting in thrombin generation
      in vivo, which leads to a hypercoagulable state and the potential to initiate
      venous or arterial thrombosis. A number of factors are thought to influence the
      incidence of HIT including the type and preparation of heparin (unfractionated
      heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed
      patient population, with the postoperative patient population at higher
      risk.Although LMWH has largely replaced UFH as a front-line therapy, there is
      evidence supporting a lack of superiority of LMWH compared with UFH regarding
      prevention of deep vein thrombosis and pulmonary embolism following surgery, and
      similar frequencies of bleeding have been described with LMWH and UFH. The
      decision as to which of these two preparations of heparin to use may thus be
      influenced by harmful effects such as HIT. We therefore sought to determine the
      relative impact of UFH and LMWH on HIT in postoperative patients receiving
      thromboembolism prophylaxis. This is an update of a review first published in
      2012. OBJECTIVES: The objective of this review was to compare the incidence of
      heparin-induced thrombocytopenia (HIT) and HIT complicated by venous
      thromboembolism in postoperative patients exposed to unfractionated heparin (UFH)
      versus low molecular weight heparin (LMWH). SEARCH METHODS: For this update, the
      Cochrane Vascular Information Specialist searched the Specialised Register (May
      2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs
      (June 2016) and additional trials were sought from reference lists of relevant
      publications. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      in which participants were postoperative patients allocated to receive
      prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were
      excluded if they did not use the accepted definition of HIT. This was defined as
      a relative reduction in the platelet count of 50% or greater from the
      postoperative peak (even if the platelet count at its lowest remained greater
      than 150 x 109/L) occurring within five to 14 days after the surgery, with or
      without a thrombotic event occurring in this timeframe. Additionally, we required
      circulating antibodies associated with the syndrome to have been investigated
      through laboratory assays. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data and assessed the risk of bias. Disagreements were
      resolved by consensus with participation of a third author. MAIN RESULTS: In this
      update, we included three trials involving 1398 postoperative participants.
      Participants were submitted to general surgical procedures, minor and major, and
      the minimum mean age was 49 years. Pooled analysis showed a significant reduction
      in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.23, 95%
      confidence interval (CI) 0.07 to 0.73); low-quality evidence. The number needed
      to treat for an additional beneficial outcome (NNTB) was 59. The risk of HIT was
      consistently reduced comparing participants undergoing major surgical procedures
      exposed to LMWH or UFH (RR 0.22, 95% CI 0.06 to 0.75); low-quality evidence. The
      occurrence of HIT complicated by venous thromboembolism was significantly lower
      in participants receiving LMWH compared with UFH (RR 0.22, 95% CI 0.06 to 0.84);
      low-quality evidence. The NNTB was 75. Arterial thrombosis occurred in only one
      participant who received UFH. There were no amputations or deaths documented.
      Although limited evidence is available, it appears that HIT induced by both types
      of heparins is common in people undergoing major surgical procedures (incidence
      greater than 1% and less than 10%). AUTHORS' CONCLUSIONS: This updated review
      demonstrated low-quality evidence of a lower incidence of HIT, and HIT
      complicated by venous thromboembolism, in postoperative patients undergoing
      thromboprophylaxis with LMWH compared with UFH. Similarily, the risk of HIT in
      people undergoing major surgical procedures was lower when treated with LMWH
      compared to UFH (low-quality evidence). The quality of the evidence was
      downgraded due to concerns about the risk of bias in the included studies and
      imprecision of the study results. These findings may support current clinical use
      of LMWH over UFH as front-line heparin therapy. However, our conclusions are
      limited and there was an unexpected paucity of RCTs including HIT as an outcome.
      To address the scarcity of clinically-relevant information on HIT, HIT must be
      included as a core harmful outcome in future RCTs of heparin.

PMID- 28431187
TI  - Feasibility of Audio-Computer-Assisted Self-Interviewing With Color-Coding and
      Helper Assistance (ACASI-H) for Hmong Older Adults.
AB  - Many older adult immigrants in the US, including Hmong older adults, have limited
      English proficiency (LEP), and cannot read or have difficulty reading even in
      their first language (non-literate [NL]). Little has been done to identify
      feasible data collection approaches to enable inclusion of LEP or NL populations
      in research, limiting knowledge about their health. This study's purpose was to
      test the feasibility of culturally and linguistically adapted audio computer
      assisted self-interviewing (ACASI) with color-labeled response categories and
      helper assistance (ACASI-H) for collection of health data with Hmong older
      adults. Thirty dyads (older adult and a helper) completed an ACASI-H survey with
      13 health questions and a face-to-face debriefing interview. ACASI-H survey
      completion was video-recorded and reviewed with participants. Video review and
      debriefing interviews were audio-recorded and transcribed. Directed and
      conventional content analyses were used to analyze the interviews. All
      respondents reported that ACASI-H survey questions were consistent with their
      health experience. They lacked computer experience and found ACASI-H's interface
      user-friendly. All used the pre-recorded Hmong oral translation except for one,
      whose helper provided translation. Some Hmong older adults struggled with the
      color labeling at first, but helpers guided them to use the colors correctly. All
      dyads liked the color-labeled response categories and confirmed that a helper was
      necessary during the survey process. Findings support use of oral survey question
      administration with a technologically competent helper and color-labeled response
      categories when engaging LEP older adults in health-related data collection. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28431188
TI  - T cell receptor beta-chain repertoire analysis reveals the association between
      neoantigens and tumour-infiltrating lymphocytes in multifocal papillary thyroid
      carcinoma.
AB  - To explore whether a few nonsynonymous somatic mutations could induce activation
      and proliferation of neoantigen-specific tumour-infiltrating lymphocytes (TILs)
      in tumours with low mutation rates, we analysed a patient with multifocal
      papillary thyroid carcinoma (seven noncontiguous cancer foci) to investigate the
      relationship between neoantigens and TILs. These seven foci had a few or no
      nonsynonymous somatic mutations; moreover, multiple loci had similar or different
      spectra of mutations. We used high-throughput sequencing of the rearranged genes
      in T cell receptor beta-chain (TCRbeta) to reveal the basic characteristics of T
      cells in seven tumour foci and matched adjacent normal tissue. We found that in
      multifocal papillary thyroid carcinoma the number of nonsynonymous somatic
      mutations was positively associated with oligoclonal TCRbeta repertoire, and
      tumour foci with similar spectra of mutations had higher overlap of TCRbeta
      repertoire. In conclusion, the number of nonsynonymous somatic mutations is small
      in tumours with low mutation rates but these mutations still play an important
      role in activating neoantigen-specific TILs.

PMID- 28431189
TI  - To CURe or not to CURe? Differential effects of the chaperone sorting factor Cur1
      on yeast prions are mediated by the chaperone Sis1.
AB  - Yeast self-perpetuating protein aggregates (prions) provide a convenient model
      for studying various components of the cellular protein quality control system.
      Molecular chaperones and chaperone-sorting factors, such as yeast Cur1 protein,
      play key role in proteostasis via tight control of partitioning and recycling of
      misfolded proteins. In this study, we show that, despite the previously described
      ability of Cur1 to antagonize the yeast prion [URE3], it enhances propagation and
      phenotypic manifestation of another prion, [PSI+ ]. We demonstrate that both
      curing of [URE3] and enhancement of [PSI+ ] in the presence of excess Cur1 are
      counteracted by the cochaperone Hsp40-Sis1 in a dosage-dependent manner, and show
      that the effect of Cur1 on prions parallels effects of the attachment of nuclear
      localization signal to Sis1, indicating that Cur1 acts on prions via its
      previously reported ability to relocalize Sis1 from the cytoplasm to nucleus.
      This shows that the direction in which Cur1 influences a prion depends on how
      this specific prion responds to relocalization of Sis1.

PMID- 28431190
TI  - Higher levels of submissive behaviors at the onset of the pairing process of
      rhesus macaques (Macaca mulatta) are associated with lower risk of wounding
      following introduction.
AB  - Social housing of rhesus macaques (Macaca mulatta) is considered to be the
      cornerstone of behavioral management programs in biomedical facilities. However,
      it also involves the risk of socially inflicted trauma. The ability to avoid such
      trauma would contribute to the animals' well-being and alleviate staff's
      concerns, thus paving the path for more introductions. Here, we sought to address
      the conflict between the need to socially house rhesus macaques and the need to
      bring social wounding to a minimum by identifying behaviors expressed early in
      social introductions, that may serve as predictors of later wounding events. We
      employed logistic regression analysis to predict the occurrence of wounding for
      39 iso-sexual, adult pairs in the 30 days following the introduction into full
      contact using the levels of behaviors that were observed at the onset of the
      introduction. The results show that the levels of submissive behaviors were the
      only significant predictor to later stage wounding. Higher levels of submissive
      behaviors expressed during the early phases of the introduction were associated
      with a decreased likelihood of wounding. Interestingly, levels of affiliative
      behaviors have not added any power to the predictability of the statistical
      model. Therefore, it may be suggested that the exchange of submissive signals at
      the earliest stages of the introduction is critical in the determination of
      relative rank and preclude the need to establish dominance via aggression when
      allowed full contact. While the observation of clear-cut dominance relationships
      is commonly considered a harbinger of success, our findings suggest that it is
      the acknowledgment of subordination, rather than the expression of dominance that
      underlies this observed pattern. The value of our findings for guiding social
      housing decision-making may be strongest in situations in which the composition
      of potential partners is constrained, and therefore requiring that wise decisions
      be relied upon early behaviors.

PMID- 28431192
TI  - A personal connection: Promoting positive attitudes towards teaching and
      learning.
AB  - Students' attitudes towards teaching and learning must be addressed with the same
      seriousness and effort as we address content. Establishing a personal connection
      and addressing our students' basic psychological needs will produce positive
      attitudes towards teaching and learning and develop life-long learners. It will
      also promote constructive student-teacher relationships that have a profound
      influence on our students' approach towards school. To begin this process,
      consider the major tenets of the Self-Determination Theory. The Self
      Determination Theory of human motivation focuses on our students' innate
      psychological needs and the degree to which an individual's behavior is self
      motivated and self-determined. Faculty can satisfy the innate psychological needs
      by addressing our students' desire for relatedness, competence and autonomy.
      Relatedness refers to our students' need to feel connected to others, to be a
      member of a group, to have a sense of communion and to develop close
      relationships with others. Competence is believing our students can succeed,
      challenging them to do so and imparting that belief in them. Autonomy involves
      considering the perspectives of the student and providing relevant information
      and opportunities for student choice and initiating and regulating their own
      behaviors. Establishing a personal connection and addressing our students' basic
      psychological needs will improve our teaching, inspire and engage our students
      and promote positive attitudes towards teaching and learning while reducing
      competition and increasing compassion. These are important goals because unless
      students are inspired and motivated and have positive attitudes towards teaching
      and learning our efforts will fail to meet their full potential. Anat Sci Educ
      10: 503-507. (c) 2017 American Association of Anatomists.

PMID- 28431191
TI  - Timing for the Introduction of Cycled Light for Extremely Preterm Infants: A
      Randomized Controlled Trial.
AB  - Day-night cycled light improves health outcomes in preterm infants, yet the best
      time to institute cycled light is unclear. The hypothesis of this study was that
      extremely preterm infants receiving early cycled light would have better health
      and developmental outcomes than infants receiving late cycled light. Infants born
      at <=28 weeks gestation were randomly assigned to early cycled light (ECL)
      starting at 28 weeks postmenstrual age [PMA] or late cycled light (LCL), starting
      at 36 weeks PMA. Daylight was 200-600 lux and night was 5-30 lux. Primary
      outcomes were weight over time and length of hospitalization. Secondary outcomes
      were hospital costs, sleep development, and neurodevelopment at 9, 18, and 24
      months corrected age. Of 121 infants randomized, 118 were included in analysis.
      Weight gain in the two groups did not differ significantly but increased across
      time in both groups. In PMA weeks 36-44, the mean weight gain was 193.8 grams in
      the ECL group compared to 176.3 grams in the LCL group. Effect sizes for weight
      were Cohen d = 0.26 and 0.36 for 36 and 44 weeks PMA. Infants in the ECL group
      went home an average of 5.5 days earlier than the LCL group, but this difference
      was not statistically significant. There were no group differences on
      neurodevelopmental outcomes. Although statistically non-significant, clinically
      important differences of improved weight gain and decreased hospital stay were
      observed with ECL. The small observed effect sizes on weight during
      hospitalization should be considered in future cycled light research with
      extremely preterm infants. (c) 2017 Wiley Periodicals, Inc.

PMID- 28431193
TI  - Evaluation of Cholesterol as a Biomarker for Suicidality in a Veteran Sample.
AB  - A reduction in total cholesterol may alter the microviscosity of the brain-cell
      membrane, reducing serotonin receptor exposure. The resulting imbalance between
      serotonin and dopamine may lead to an increased risk for suicidality. The
      objective of this research was to evaluate total cholesterol as a biological
      marker for suicidality in a sample of US military veterans. The study population
      consisted of veterans who received care at the Coatesville Veterans Affairs
      Medical Center (VAMC) and were included in the Suicide Prevention Coordinator's
      database for having suicidal ideation with evidence of escalating intent, a
      documented suicide attempt, or committed suicide between 2009 and 2015. The
      veterans' medical data were obtained from the facility's computerized patient
      record system. The final sample was 188 observations from 128 unique veterans.
      Veterans with total cholesterol levels below 168 mg/dl appeared to have a higher
      suicide risk than those with higher levels. The cholesterol levels of veterans
      reporting suicidal ideation or attempt were significantly lower than the group
      reporting neither [F(2, 185) = 30.19, p < .001]. When data from multiple visits
      were available, veterans reporting suicidal ideation or attempt had experienced a
      significant (20%) decrease in cholesterol levels from an earlier visit in which
      they did not report suicidality. A latent class analysis revealed that among
      other differences, suicidal veterans were younger, leaner, and had more anxiety,
      sleep problems, and higher education than those being seen for an issue unrelated
      to suicidality. (c) 2017 Wiley Periodicals, Inc.

PMID- 28431194
TI  - Closed-form equation to estimate the dielectric properties of biological tissues
      as a function of age.
AB  - Developing microwave systems for biomedical applications requires accurate
      dielectric properties of biological tissues for reliable modeling before
      prototyping and subject testing. Dielectric properties of tissues decrease with
      age due to the change in their water content, but there are no detailed age
      dependent data, especially for young tissue-like newborns, in the literature. In
      this article, an age-dependent formula to predict the dielectric properties of
      biological tissues was derived. In the proposed method, the variation of water
      concentration in each type of tissue as a function of age was used to calculate
      its relative permittivity and conductivity. The derived formula shows that the
      concentration of water in each tissue type can be modeled as a negative
      exponential function of age. The dielectric properties of each tissue type can
      then be calculated as a function of the dielectric properties of water and
      dielectric properties of the organ forming the tissue and its water
      concentration. The derived formula was used to generate the dielectric properties
      of several types of human tissues at different ages using the dielectric
      properties of a human adult. Moreover, the formula was validated on pig tissues
      of different ages. A close agreement was achieved between the calculated and
      measured data with a maximum difference of only 2%. Bioelectromagnetics. 38:474
      481, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28431195
TI  - Feeding behavior and activity budget of the southern yellow-cheeked crested
      gibbons (Nomascus gabriellae) in a lowland tropical forest.
AB  - The southern yellow-cheeked crested gibbon (Nomascus gabriellae), an endangered
      species native to Vietnam and Cambodia, lives exclusively in undisturbed tropical
      forests and depends primarily on ripe fruit for food. Although this species is
      highly threatened, its ecology and conservation status remain relatively unknown.
      In order to understand how this heavily frugivorous primate adapts to the
      seasonal fluctuation of fruit resources in the forest, we collected feeding
      behavior and ranging activity data on one group of southern yellow-cheeked
      crested gibbons in Cat Tien National Park, Vietnam, over 1-year period. We
      compared these data to information on phenological patterns at the site gleaned
      during a prior study. We found that the gibbons gathered most of their food from
      69 different plant species and also consumed insects and bird eggs. Fruits were
      the main dietary item (43.3%), followed by leaves (38.4%), flowers (11.6%), and
      other plant parts (6.0%). A significant seasonal shift in diet was observed;
      fruit generally dominated the diet in the rainy season and leaves in the dry
      season. The gibbons often started daily activities very early (05:10 am) in the
      morning and also ended quite early (16:45 pm) in the afternoon. Socializing was
      concentrated in the early morning, feeding had a bimodal pattern of high activity
      levels in mid-morning and mid-afternoon, and resting was most intense at the
      earliest and latest hours of the day and at midday, with proportionally less time
      used for traveling at these times. Averaged over the annual cycle, the gibbons
      spent 45% of their time feeding, 31.9% resting, 14.1% traveling, and 9.0%
      socializing. The percentage of time allocated to different activities varied
      significantly across months and between the dry and rainy seasons. Monthly
      variation in the activity budget was strongly related to changes in diet. In the
      rainy season, when the gibbons ate a higher percentage of fruit, they decreased
      their feeding time, while increasing traveling time in search of food;
      conversely, in the dry season, when they fed on a higher percentage of leaves,
      they decreased traveling time. Overall, our results show that the activity budget
      and diet of the southern yellow-cheeked crested gibbon are associated with
      seasonal shifts in climate. This study provides information relevant to the
      conservation and management of this endangered species by identifying important
      habitat conditions for reintroducing captive animals into the wild and providing
      insight into dietary needs, which may be relevant to the maintenance of animals
      in rescue centers.

PMID- 28431196
TI  - Switch to Abobotulinum toxin A may be useful in the treatment of neurogenic
      detrusor overactivity when intradetrusor injections of Onabotulinum toxin A
      failed.
AB  - AIMS: To assess the outcomes of switching to a different brand of botulinum toxin
      A (BTA, from Botox(r) to Dysport(r)) in case of failure of intradetrusor
      injections (IDI) of Botox(r) in the treatment of neurogenic detrusor overactivity
      (NDO). METHODS: The charts of all patients who underwent a switch to IDI of
      Dysport(r) after failure of an IDI of Botox(r) at six departments of neurourology
      were retrospectively reviewed. The main outcomes of interest were the bladder
      diary data and four urodynamic parameters: maximum cystometric capacity (MCC),
      maximum detrusor pressure (PDET max), and volume at first uninhibited detrusor
      contraction (UDC). RESULTS: Fifty-seven patients were included. After the first
      injection of Dysport(r), no adverse events were reported. A significant decrease
      in number of urinary incontinence episodes per day was observed in 52.63% of
      patients (P < 0.001) and all patients experienced a reduction in PDET Max (-8.1
      cmH20 on average; P = 0.003). MCC significantly increased by a mean of 41.2 (P =
      0.02). The proportion of patients with no UDC increased significantly at week 6
      after ATA injections (from 15.79% to 43.9%; P = 0.0002). Hence, 32 patients draw
      clinical and/or urodynamic benefits from the botulinum toxin switch from
      (56.14%). After a median follow up of 21 months, 87% of responders to BTA switch
      were still treated successfully with BTA. CONCLUSION: Most patients refractory to
      Botox(r) (56.14%) draw benefits from the switch to Dysport(r).

PMID- 28431197
TI  - Serum C-reactive protein, procalcitonin, and lactate dehydrogenase for the
      diagnosis of pancreatic necrosis.
AB  - BACKGROUND: The treatment of people with pancreatic necrosis differs from that of
      people with oedematous pancreatitis. It is important to know the diagnostic
      accuracy of serum C-reactive protein (CRP), serum procalcitonin, and serum
      lactate dehydrogenase (LDH) as a triage test for the detection of pancreatic
      necrosis in people with acute pancreatitis, so that an informed decision can be
      made as to whether the person with pancreatic necrosis needs further
      investigations such as computed tomography (CT) scan or magnetic resonance
      imaging (MRI) scan and treatment for pancreatic necrosis started. There is
      currently no standard clinical practice, although CRP, particularly an increasing
      trend of CRP, is often used as a triage test to determine whether the person
      requires further imaging. There is also currently no systematic review of the
      diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of
      pancreatic necrosis in people with acute pancreatitis. OBJECTIVES: To compare the
      diagnostic accuracy of CRP, procalcitonin, or LDH (index test), either alone or
      in combination, in the diagnosis of necrotising pancreatitis in people with acute
      pancreatitis and without organ failure. SEARCH METHODS: We searched MEDLINE,
      Embase, Science Citation Index Expanded, National Institute for Health Research
      (NIHR HTA and DARE), and other databases until March 2017. We searched the
      references of the included studies to identify additional studies. We did not
      restrict studies based on language or publication status, or whether data were
      collected prospectively or retrospectively. We also performed a 'related search'
      and 'citing reference' search in MEDLINE and Embase. SELECTION CRITERIA: We
      included all studies that evaluated the diagnostic test accuracy of CRP,
      procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with
      acute pancreatitis using the following reference standards, either alone or in
      combination: radiological features of pancreatic necrosis (contrast-enhanced CT
      or MRI), surgeon's judgement of pancreatic necrosis during surgery, or
      histological confirmation of pancreatic necrosis. Had we found case-control
      studies, we planned to exclude them because they are prone to bias; however, we
      did not locate any. Two review authors independently identified the relevant
      studies from the retrieved references. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data, including methodological quality
      assessment, from the included studies. As the included studies reported CRP,
      procalcitonin, and LDH on different days of admission and measured at different
      cut-off levels, it was not possible to perform a meta-analysis using the
      bivariate model as planned. We have reported the sensitivity, specificity, post
      test probability of a positive and negative index test along with 95% confidence
      interval (CI) on each of the different days of admission and measured at
      different cut-off levels. MAIN RESULTS: A total of three studies including 242
      participants met the inclusion criteria for this review. One study reported the
      diagnostic performance of CRP for two threshold levels (> 200 mg/L and > 279
      mg/L) without stating the day on which the CRP was measured. One study reported
      the diagnostic performance of procalcitonin on day 1 (1 day after admission)
      using a threshold level of 0.5 ng/mL. One study reported the diagnostic
      performance of CRP on day 3 (3 days after admission) using a threshold level of
      140 mg/L and LDH on day 5 (5 days after admission) using a threshold level of 290
      U/L. The sensitivities and specificities varied: the point estimate of the
      sensitivities ranged from 0.72 to 0.88, while the point estimate of the
      specificities ranged from 0.75 to 1.00 for the different index tests on different
      days of hospital admission. However, the confidence intervals were wide:
      confidence intervals of sensitivities ranged from 0.51 to 0.97, while those of
      specificities ranged from 0.18 to 1.00 for the different tests on different days
      of hospital admission. Overall, none of the tests assessed in this review were
      sufficiently accurate to suggest that they could be useful in clinical practice.
      AUTHORS' CONCLUSIONS: The paucity of data and methodological deficiencies in the
      studies meant that it was not possible to arrive at any conclusions regarding the
      diagnostic test accuracy of the index test because of the uncertainty of the
      results. Further well-designed diagnostic test accuracy studies with prespecified
      index test thresholds of CRP, procalcitonin, LDH; appropriate follow-up (for at
      least two weeks to ensure that the person does not have pancreatic necrosis, as
      early scans may not indicate pancreatic necrosis); and clearly defined reference
      standards (of surgical or radiological confirmation of pancreatic necrosis) are
      important to reliably determine the diagnostic accuracy of CRP, procalcitonin,
      and LDH.

PMID- 28431198
TI  - Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of
      acute pancreatitis.
AB  - BACKGROUND: The treatment of people with acute abdominal pain differs if they
      have acute pancreatitis. It is important to know the diagnostic accuracy of serum
      amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the
      diagnosis of acute pancreatitis, so that an informed decision can be made as to
      whether the person with abdominal pain has acute pancreatitis. There is currently
      no Cochrane review of the diagnostic test accuracy of serum amylase, serum
      lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute
      pancreatitis. OBJECTIVES: To compare the diagnostic accuracy of serum amylase,
      serum lipase, urinary trypsinogen-2, and urinary amylase, either alone or in
      combination, in the diagnosis of acute pancreatitis in people with acute onset of
      a persistent, severe epigastric pain or diffuse abdominal pain. SEARCH METHODS:
      We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute
      for Health Research (NIHR HTA and DARE), and other databases until March 2017. We
      searched the references of the included studies to identify additional studies.
      We did not restrict studies based on language or publication status, or whether
      data were collected prospectively or retrospectively. We also performed a
      'related search' and 'citing reference' search in MEDLINE and Embase. SELECTION
      CRITERIA: We included all studies that evaluated the diagnostic test accuracy of
      serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the
      diagnosis of acute pancreatitis. We excluded case-control studies because these
      studies are prone to bias. We accepted any of the following reference standards:
      biopsy, consensus conference definition, radiological features of acute
      pancreatitis, diagnosis of acute pancreatitis during laparotomy or autopsy, and
      organ failure. At least two review authors independently searched and screened
      the references located by the search to identify relevant studies. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data from the
      included studies. The thresholds used for the diagnosis of acute pancreatitis
      varied in the trials, resulting in sparse data for each index test. Because of
      sparse data, we used -2 log likelihood values to determine which model to use for
      meta-analysis. We calculated and reported the sensitivity, specificity, post-test
      probability of a positive and negative index test along with 95% confidence
      interval (CI) for each cutoff, but have reported only the results of the
      recommended cutoff of three times normal for serum amylase and serum lipase, and
      the manufacturer-recommended cutoff of 50 mg/mL for urinary trypsinogen-2 in the
      abstract. MAIN RESULTS: Ten studies including 5056 participants met the inclusion
      criteria for this review and assessed the diagnostic accuracy of the index tests
      in people presenting to the emergency department with acute abdominal pain. The
      risk of bias was unclear or high for all of the included studies. The study that
      contributed approximately two-thirds of the participants included in this review
      was excluded from the results of the analysis presented below due to major
      concerns about the participants included in the study. We have presented only the
      results where at least two studies were included in the analysis.Serum amylase,
      serum lipase, and urinary trypsinogen-2 at the standard threshold levels of more
      than three times normal for serum amylase and serum lipase, and a threshold of 50
      ng/mL for urinary trypsinogen-2 appear to have similar sensitivities (0.72 (95%
      CI 0.59 to 0.82); 0.79 (95% CI 0.54 to 0.92); and 0.72 (95% CI 0.56 to 0.84),
      respectively) and specificities (0.93 (95% CI 0.66 to 0.99); 0.89 (95% CI 0.46 to
      0.99); and 0.90 (95% CI 0.85 to 0.93), respectively). At the median prevalence of
      22.6% of acute pancreatitis in the studies, out of 100 people with positive test,
      serum amylase (more than three times normal), serum lipase (more than three times
      normal), and urinary trypsinogen (more than 50 ng/mL), 74 (95% CI 33 to 94); 68
      (95% CI 21 to 94); and 67 (95% CI 57 to 76) people have acute pancreatitis,
      respectively; out of 100 people with negative test, serum amylase (more than
      three times normal), serum lipase (more than three times normal), and urinary
      trypsinogen (more than 50 ng/mL), 8 (95% CI 5 to 12); 7 (95% CI 3 to 15); and 8
      (95% CI 5 to 13) people have acute pancreatitis, respectively. We were not able
      to compare these tests formally because of sparse data. AUTHORS' CONCLUSIONS: As
      about a quarter of people with acute pancreatitis fail to be diagnosed as having
      acute pancreatitis with the evaluated tests, one should have a low threshold to
      admit the patient and treat them for acute pancreatitis if the symptoms are
      suggestive of acute pancreatitis, even if these tests are normal. About 1 in 10
      patients without acute pancreatitis may be wrongly diagnosed as having acute
      pancreatitis with these tests, therefore it is important to consider other
      conditions that require urgent surgical intervention, such as perforated viscus,
      even if these tests are abnormal.The diagnostic performance of these tests
      decreases even further with the progression of time, and one should have an even
      lower threshold to perform additional investigations if the symptoms are
      suggestive of acute pancreatitis.

PMID- 28431200
TI  - The utility of flow cytometry in differentiating NK/T cell lymphoma from indolent
      and reactive NK cell proliferations.
AB  - BACKGROUND: The WHO defines three categories of NK cell malignancies; extra nodal
      NK/T cell lymphoma (NKTCL), aggressive NK cell leukemia, and the provisional
      entity chronic lymphoproliferative disorder of NK cells (CLPD-NK). Although the
      flow cytometric (FC) phenotype of CLPD-NK has been described, studies on FC
      phenotype of NKTCL are limited. To the best of our knowledge ours is the first
      study to compare the phenotype of NKTCL, CLPD-NK, reactive NK lymphocytosis
      (RNKL), and normal NK cells using eight color (8C) FC. METHODS: Specimens
      analyzed using the Euroflow8C NK Lymphoproliferative Disorder (NKLPD) panel
      between 2011 and 2014 were identified from our database. All samples were
      analyzed on the FACSCantoII cytometer. NK cells were identified as CD45+, smCD3-,
      CD19-, CD56+ and normal T-cells served as internal controls. RESULTS: The
      majority of NKTCL were CD56 bright, CD16 dim, CD57-, and CD94+. CLPD-NK and RNKL
      were predominantly CD56+ or dim with positive expression of CD16 and CD57 and
      weak CD94 expression. Antigen based statistical analyses showed robust division
      of samples along the NKTCL/normal CD56 bright NK cell and CLPD-NK/RNKL/normal
      CD56 positive NK cell groups. CONCLUSIONS: It was concluded that FC can reliably
      distinguish NKTCL from CLPD-NK, normal NK cells of CD56+ phenotype, and RNKL. It
      was proposed that the typical phenotype for NKTCL is: CD56 bright, CD16 dim with
      positive CD2, CD7, CD94, HLADR, CD25, CD26, and absent CD57. This resembles the
      phenotype of the CD56 bright immunoregulatory subset of NK cells which we
      therefore hypothesize is the cell of origin of NKTCL. (c) 2017 International
      Clinical Cytometry Society.

PMID- 28431201
TI  - Teaching neuroanatomy using computer-aided learning: What makes for successful
      outcomes?
AB  - Computer-aided learning (CAL) is an integral part of many medical courses. The
      neuroscience course at Oxford University for medical students includes CAL course
      of neuroanatomy. CAL is particularly suited to this since neuroanatomy requires
      much detailed three-dimensional visualization, which can be presented on screen.
      The CAL course was evaluated using the concept of approach to learning. The aims
      of university teaching are congruent with the deep approach-seeking meaning and
      relating new information to previous knowledge-rather than to the surface
      approach of concentrating on rote learning of detail. Seven cohorts of medical
      students (N = 869) filled in approach to learning scale and a questionnaire
      investigating their engagement with the CAL course. The students' scores on CAL
      course-based neuroanatomy assessment and later university examinations were
      obtained. Although the students reported less use of the deep approach for the
      neuroanatomy CAL course than for the rest of their neuroanatomy course (mean =
      24.99 vs. 31.49, P < 0.001), deep approach for CAL was positively correlated with
      neuroanatomy assessment performance (r = 0.12, P < 0.001). Time spent on the CAL
      course, enjoyment of it, the amount of CAL videos watched and quizzes completed
      were each significantly positively related to deep approach. The relationship
      between deep approach and enjoyment was particularly notable (25.5% shared
      variance). Reported relationships between deep approach and academic performance
      support the desirability of deep approach in university students. It is proposed
      that enjoyment of the course and the deep approach could be increased by
      incorporation of more clinical material which is what the students liked most.
      Anat Sci Educ 10: 560-569. (c) 2017 American Association of Anatomists.

PMID- 28431202
TI  - Pharmacological interventions for acute pancreatitis.
AB  - BACKGROUND: In people with acute pancreatitis, it is unclear what the role should
      be for medical treatment as an addition to supportive care such as fluid and
      electrolyte balance and organ support in people with organ failure. OBJECTIVES:
      To assess the effects of different pharmacological interventions in people with
      acute pancreatitis. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation
      Index Expanded, and trial registers to October 2016 to identify randomised
      controlled trials (RCTs). We also searched the references of included trials to
      identify further trials. SELECTION CRITERIA: We considered only RCTs performed in
      people with acute pancreatitis, irrespective of aetiology, severity, presence of
      infection, language, blinding, or publication status for inclusion in the review.
      DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials
      and extracted data. We did not perform a network meta-analysis as planned because
      of the lack of information on potential effect modifiers and differences of type
      of participants included in the different comparisons, when information was
      available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs)
      for the binary outcomes and rate ratios with 95% CIs for count outcomes using a
      fixed-effect model and random-effects model. MAIN RESULTS: We included 84 RCTs
      with 8234 participants in this review. Six trials (N = 658) did not report any of
      the outcomes of interest for this review. The remaining 78 trials excluded 210
      participants after randomisation. Thus, a total of 7366 participants in 78 trials
      contributed to one or more outcomes for this review. The treatments assessed in
      these 78 trials included antibiotics, antioxidants, aprotinin, atropine,
      calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate,
      glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs),
      octreotide, oxyphenonium, probiotics, activated protein C, somatostatin,
      somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin,
      ulinastatin, and inactive control. Apart from the comparison of antibiotics
      versus control, which included a large proportion of participants with
      necrotising pancreatitis, the remaining comparisons had only a small proportion
      of patients with this condition. Most trials included either only participants
      with severe acute pancreatitis or included a mixture of participants with mild
      acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk
      of bias in trials was unclear or high for all but one of the trials. SOURCE OF
      FUNDING: seven trials were not funded or funded by agencies without vested
      interest in results. Pharmaceutical companies partially or fully funded 21
      trials. The source of funding was not available from the remaining trials.Since
      we considered short-term mortality as the most important outcome, we presented
      only these results in detail in the abstract. Sixty-seven studies including 6638
      participants reported short-term mortality. There was no evidence of any
      differences in short-term mortality in any of the comparisons (very low-quality
      evidence). With regards to other primary outcomes, serious adverse events
      (number) were lower than control in participants taking lexipafant (rate ratio
      0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence),
      octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low
      quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to
      0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin
      (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence).
      The proportion of people with organ failure was lower in octreotide than control
      (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence).
      The proportion of people with sepsis was lower in lexipafant than control (OR
      0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There
      was no evidence of differences in any of the remaining comparisons in these
      outcomes or for any of the remaining primary outcomes (the proportion of
      participants experiencing at least one serious adverse event and the occurrence
      of infected pancreatic necrosis). None of the trials reported heath-related
      quality of life. AUTHORS' CONCLUSIONS: Very low-quality evidence suggests that
      none of the pharmacological treatments studied decrease short-term mortality in
      people with acute pancreatitis. However, the confidence intervals were wide and
      consistent with an increase or decrease in short-term mortality due to the
      interventions. We did not find consistent clinical benefits with any
      intervention. Because of the limitations in the prognostic scoring systems and
      because damage to organs may occur in acute pancreatitis before they are
      clinically manifest, future trials should consider including pancreatitis of all
      severity but power the study to measure the differences in the subgroup of people
      with severe acute pancreatitis. It may be difficult to power the studies based on
      mortality. Future trials in participants with acute pancreatitis should consider
      other outcomes such as complications or health-related quality of life as primary
      outcomes. Such trials should include health-related quality of life, costs, and
      return to work as outcomes and should follow patients for at least three months
      (preferably for at least one year).

PMID- 28431199
TI  - Staphylococcus aureus nitric oxide synthase (saNOS) modulates aerobic respiratory
      metabolism and cell physiology.
AB  - Nitric oxide (NO) is generated from arginine and oxygen via NO synthase (NOS).
      Staphylococcus aureus NOS (saNOS) has previously been shown to affect virulence
      and resistance to exogenous oxidative stress, yet the exact mechanism is unknown.
      Herein, a previously undescribed role of saNOS in S. aureus aerobic physiology
      was reported. Specifically, aerobic S. aureus nos mutant cultures presented with
      elevated endogenous reactive oxygen species (ROS) and superoxide levels, as well
      as increased membrane potential, increased respiratory dehydrogenase activity and
      slightly elevated oxygen consumption. Elevated ROS levels in the nos mutant
      likely resulted from altered respiratory function, as inhibition of NADH
      dehydrogenase brought ROS levels back to wild-type levels. These results indicate
      that, in addition to its recently reported role in regulating the switch to
      nitrate-based respiration during low-oxygen growth, saNOS also plays a modulatory
      role during aerobic respiration. Multiple transcriptional changes were also
      observed in the nos mutant, including elevated expression of genes associated
      with oxidative/nitrosative stress, anaerobic respiration and lactate metabolism.
      Targeted metabolomics revealed decreased cellular lactate levels, and altered
      levels of TCA cycle intermediates, the latter of which may be related to
      decreased aconitase activity. Collectively, these findings demonstrate a key
      contribution of saNOS to S. aureus aerobic respiratory metabolism.

PMID- 28431204
TI  - Factors that affect outcomes of prolapse repair using single-incision vaginal
      mesh procedures.
AB  - AIMS: Single-incision vaginal mesh (SIVM) procedures for pelvic organ prolapse
      (POP) differed in mesh fabrication and implantation that may affect treatment
      outcomes. We aim to evaluate and compare the safety and effectiveness of two SIVM
      procedures, and explore factors that may have associations with surgical
      effectiveness. METHODS: Our data of using two SIVM procedures for a total
      (anterior and posterior) vaginal mesh repair were studied. Patients who had
      ?stage 2 POP and underwent either Elevate (n = 85) using anchored, lightweight
      meshes or Prosima procedures (n = 95) using non-anchored, original meshes were
      assessed. A detailed comparison of 1 year outcomes was made. RESULTS: Of the 180
      patients, 172 (95.6%) attended the 1-year follow-up. Demographic data were
      similar between groups except a higher average age (64.5 vs 60.4, P = 0.001) was
      noted in the Elevate (n = 84) group compared to the Prosima (n = 88) group.
      Surgical results were also similar except a significantly higher objective cure
      (POP stage ?1) rate (89.3% vs 78.4%, P = 0.042) was noted in the Elevate group.
      The safety profile favored Elevate with a lower, but not statistically
      significant, rate (4.7% vs 12.5%, P = 0.106) of vaginal mesh exposure. After a
      statistical analysis, we found anatomic recurrence (POP stage ?2) after the SIVM
      procedures had strong (P < 0.05) associations with "early surgical cases,"
      "Prosima procedure," "advanced cystocele (Ba > +3 cm)," and "prior prolapse
      repair," respectively. CONCLUSIONS: Beyond a learning curve, Elevate performed
      better than Prosima in POP repair regarding surgical effectiveness. Meanwhile,
      several predisposing factors that may affect recurrence after SIVM procedures
      were found.

PMID- 28431203
TI  - Donor safety in living donor liver transplantation: The Korean organ
      transplantation registry study.
AB  - Major concerns about donor safety cause controversy and limit the use of living
      donor liver transplantation to overcome organ shortages. The Korean Organ
      Transplantation Registry established a nationwide organ transplantation
      registration system in 2014. We reviewed the prospectively collected data of all
      832 living liver donors who underwent procedures between April 2014 and December
      2015. We allocated the donors to a left lobe group (n = 59) and a right lobe
      group (n = 773) and analyzed the relations between graft types and remaining
      liver volumes and complications (graded using the Clavien 5-tier grading system).
      The median follow-up was 19 months (range, 10-31 months). During the study
      period, 553 men and 279 women donated livers, and there were no deaths after
      living liver donation. The overall, biliary, and major complication (grade >=
      III) rates were 9.3%, 1.7%, and 1.9%, respectively. The graft types and remaining
      liver volume were associated with significantly different overall, biliary, and
      major complication rates. Of the 16 patients with major complications, 9 (56.3%)
      involved biliary complications (2 biliary strictures [12.5%] and 7 bile leakages
      [43.8%]). Among the 832 donors, the mean aspartate transaminase, alanine
      aminotransferase, and total bilirubin levels were 23.9 +/- 8.1 IU/L, 20.9 +/-
      11.3 IU/L, and 0.8 +/- 0.4 mg/dL, respectively, 6 months after liver donation. In
      conclusion, biliary complications were the most common types of major morbidity
      in living liver donors. Donor hepatectomy can be performed successfully with
      minimal and easily controlled complications. Our study shows that prospective,
      nationwide cohort data provide an important means of investigating the safety in
      living liver donation. Liver Transplantation 23 999-1006 2017 AASLD.

PMID- 28431205
TI  - Cyclization of Ynamide-Tethered 1,3,8-Triynes.
AB  - A facile thermal cyclization of ynamide-tethered 1,3,8-triynes to form a 3,5,6,7
      tetrahydro-1H-pyrano[3,4-c]pyridine skeleton is described. Although the mechanism
      of this unusual reaction has yet to be defined, the formation of either a
      strained keteniminium or a biradical intermediate followed by a 1,5-hydride or 
      hydrogen shift is tentatively proposed as the key elementary steps in the
      reaction sequence. Appropriate electronic activation at the carbon center
      donating a hydride or hydrogen is crucial for successful cyclization.

PMID- 28431206
TI  - Phase-Transfer Ligand Exchange of Lead Chalcogenide Quantum Dots for Direct
      Deposition of Thick, Highly Conductive Films.
AB  - The use of semiconductor nanocrystal quantum dots (QDs) in optoelectronic devices
      typically requires postsynthetic chemical surface treatments to enhance
      electronic coupling between QDs and allow for efficient charge transport in QD
      films. Despite their importance in solar cells and infrared (IR) light-emitting
      diodes and photodetectors, advances in these chemical treatments for lead
      chalcogenide (PbE; E = S, Se, Te) QDs have lagged behind those of, for instance,
      II-VI semiconductor QDs. Here, we introduce a method for fast and effective
      ligand exchange for PbE QDs in solution, resulting in QDs completely passivated
      by a wide range of small anionic ligands. Due to electrostatic stabilization,
      these QDs are readily dispersible in polar solvents, in which they form highly
      concentrated solutions that remain stable for months. QDs of all three Pb
      chalcogenides retain their photoluminescence, allowing for a detailed study of
      the effect of the surface ionic double layer on electronic passivation of QD
      surfaces, which we find can be explained using the hard/soft acid-base theory.
      Importantly, we prepare highly conductive films of PbS, PbSe, and PbTe QDs by
      directly casting from solution without further chemical treatment, as determined
      by field-effect transistor measurements. This method allows for precise control
      over the surface chemistry, and therefore the transport properties of deposited
      films. It also permits single-step deposition of films of unprecedented thickness
      via continuous processing techniques, as we demonstrate by preparing a dense,
      smooth, 5.3-MUm-thick PbSe QD film via doctor-blading. As such, it offers
      important advantages over laborious layer-by-layer methods for solar cells and
      photodetectors, while opening the door to new possibilities in ionizing-radiation
      detectors.

PMID- 28431207
TI  - Syntheses of Chroman-2-ones and alpha-Amino Acids through a Diastereoselective
      Domino Reaction.
AB  - Many 3-aminochroman-2-ones and beta,beta-diarylalanines exhibit significant
      biological activities. A new method was thus developed for the syntheses of these
      compounds with high efficiency and diastereoselectivity. First, treatment of
      various phenols with Erlenmeyer-Plochl (Z)-azlactones and AlCl3 in toluene
      produced the desired cis-3-aminochroman-2-ones in 65-90% yields under kinetic
      control. This coupling reaction involved a domino process of Friedel-Crafts
      alkylation, 1,4-AlCl3 shift, transesterification, and protodealumination in a
      "single-flask." The corresponding products, however, were not generated by
      replacement of AlCl3 with a protonic acid. Second, hydrolysis of the resultant 3
      amino-4-arylchroman-2-ones by NaHCO3 in a mixture of THF and water gave alpha-(N
      benzoyl)amino acids. Further deprotection of these isolated compounds by use of
      hydrochloric acid (12 N) in methanol afforded the desired free amino acids in 80
      88% yields. Under these optimized conditions, epimerization did not occur at the
      alpha carbons of alpha-(N-benzoyl)- and free alpha-amino acids. These new
      findings provide a convenient way to generate 3,4-disubtituted chroman-2-ones and
      beta,beta-diarylalanine derivatives with very high stereoselectivity.

PMID- 28431208
TI  - Copper-Catalyzed Chemoselective and Enantioselective Friedel-Crafts 1,2-Addition
      of Pyrrole with beta,gamma-Unsaturated alpha-Ketoesters.
AB  - A Friedel-Crafts alkylation of pyrrole was developed to afford the beta,gamma
      unsaturated alpha-hydroxy esters bearing a quaternary stereogenic center with
      good enantioselectivities and yields. This protocol represents the first report
      of 1,2-addition of Friedel-Crafts alkylation of pyrrole to beta,gamma-unsaturated
      alpha-ketoesters.

PMID- 28431209
TI  - Drug Delivery Systems Based on Hydroxyethyl Starch.
AB  - The advantageous biological properties of hydroxyethyl starch (HES) triggered
      research interest toward the design and synthesis of drug delivery systems (DDSs)
      based on this polysaccharide. Convenient reaction schemes, including one-step
      reactions, led to the synthesis of HES conjugates with selected anticancer
      molecules or therapeutic proteins. Nanocapsules and hydrogels based on HES were
      also prepared and studied as prospective drug delivery systems. Formulations
      originating from these drug conjugates and also from nanocapsules and hydrogels
      loaded with drugs were characterized, highlighting the extension of their half
      life in plasma, which is a critical property as far as their efficacy is
      concerned. Results obtained in vitro and in vivo proved promising, justifying the
      undertaking of additional experiments with such systems, including their
      multifunctionalization. The promising formulations that are discussed in this
      Topical Review is expected to further increase interest in applying HES for
      molecular constructing novel DDSs with enhanced efficacy, which may, in the
      future, find clinical applications.

PMID- 28431210
TI  - Exotic "Gill Lice" Species (Copepoda: Lernaeopodidae: Salmincola SPP.) Infect
      Rainbow Trout (Oncorhynchus mykiss) and Brook Trout (Salvelinus fontinalis) in
      the Southeastern United States.
AB  - Salmincola californiensis infected 25 of 31 (prevalence 0.8; intensity 2-35 [mean
      6.6 +/- standard deviation 7.7; n = 25]) rainbow trout, Oncorhynchus mykiss, from
      a private trout farm connected to the Watauga River, North Carolina. Salmincola
      edwardsii infected all of 9 (1.0; 2-43 [9.3 +/- 13.0; 9]) brook trout, Salvelinus
      fontinalis, from Big Norton Prong, a tributary of the Little Tennessee River,
      North Carolina. Both lernaeopodids are well-known salmonid pathogens, but neither
      is native to, nor has been previously taxonomically confirmed from, the
      southeastern United States. Herein, we (1) use light and scanning electron
      microscopy to identify and provide supplemental morphological observations of
      these lernaeopodids, (2) furnish complementary molecular sequence data from the
      28S rDNA (28S), and (3) document the pathological effects of gill infections. We
      identified and differentiated these lernaeopodids by the second antenna (exopod
      tip with large [S. californiensis] vs. slender [S. edwardsii] spines; endopod
      terminal segment with subequal ventral processes shorter than [S. californiensis]
      vs. longer than or equal to [S. edwardsii] dorsal hook), maxilliped palp (length
      typically <=1/3 [S. californiensis] vs. 1/3-1/2 [S. edwardsii] subchela length
      exclusive of claw), and bulla (sub-circular and concave on manubrium's side [S.
      californiensis] vs. non-stellate [S. edwardsii]). Analysis of the 28S rDNA
      sequences confirmed our taxonomic assignments as demonstrated by 100% sequence
      similarity among the sympatric, morphologically-conspecific isolates.
      Histopathology revealed focal gill epithelial hyperplasia, obstruction of
      interlamellar water channels, lamellar fusion, and crypting of gill filaments.
      High intensity infections by either lernaeopodid are surveillance-worthy because
      they are potentially pathogenic to trout in the southeastern United States.

PMID- 28431211
TI  - Oxyuricassis coronatus n. gen. n. sp. and O. hexaspinatus n. sp. (Oxyurida:
      Pharyngodonidae): Parasites of Lasiancistrus saetiger (Siluriformes:
      Loricariidae) in Freshwater Rivers of the Brazilian Amazon.
AB  - A new nematode genus is described from intestines of Lasiancistrus saetiger
      Ambruster from freshwater rivers in the Brazilian Amazon. Oxyuricassis n. gen. is
      characterized by a cephalic cone, small buccal cavity, long esophagus with a well
      developed isthmus, and a conical tail with spines. Two new species are described:
      Oxyuricassis coronatus n. sp. is characterized by the absence of lateral alae, a
      conical tail with truncated extremity with spine-like sclerotized projections
      around the tail tip, and caudal alae in males expanded. Oxyuricassis hexaspinatus
      n. sp. is characterized by lateral alae, a conical tail with tapered extremity,
      with 2 pairs of proximal spines at the posterior extremity of the tail, 1 dorsal
      pair and 1 ventral pair, plus a pair of lateral spines that vary in position
      between sexes, and male of O. hexaspinatus has narrow caudal alae. Both species
      were found co-parasitizing all of the analyzed host specimens.

PMID- 28431212
TI  - DNA barcoding and traditional taxonomy: an integrated approach for biodiversity
      conservation.
AB  - Biological diversity is depleting at an alarming rate. Additionally, a vast
      amount of biodiversity still remains undiscovered. Taxonomy has been serving the
      purpose of describing, naming, and classifying species for more than 250 years.
      DNA taxonomy and barcoding have accelerated the rate of this process, thereby
      providing a tool for conservation practice. DNA barcoding and traditional
      taxonomy have their own inherent merits and demerits. The synergistic use of both
      methods, in the form of integrative taxonomy, has the potential to contribute to
      biodiversity conservation in a pragmatic timeframe and overcome their individual
      drawbacks. In this review, we discuss the basics of both these methods of
      biological identification (traditional taxonomy and DNA barcoding), the technical
      advances in integrative taxonomy, and future trends. We also present a
      comprehensive compilation of published examples of integrative taxonomy that
      refer to nine topics within biodiversity conservation. Morphological and
      molecular species limits were observed to be congruent in ~41% of the 58 source
      studies. The majority of the studies highlighted the description of cryptic
      diversity through the use of molecular data, whereas research areas like
      endemism, biological invasion, and threatened species were less discussed in the
      literature.

PMID- 28431213
TI  - Genome mining unearths a hybrid nonribosomal peptide synthetase-like-pteridine
      synthase biosynthetic gene cluster.
AB  - Nonribosomal peptides represent a large class of metabolites with pharmaceutical
      relevance. Pteridines, such as pterins, folates, and flavins, are heterocyclic
      metabolites that often serve as redox-active cofactors. The biosynthetic
      machineries for construction of these distinct classes of small molecules operate
      independently in the cell. Here, we discovered an unprecedented nonribosomal
      peptide synthetase-like-pteridine synthase hybrid biosynthetic gene cluster in
      Photorhabdus luminescens using genome synteny analysis. P. luminescens is a
      Gammaproteobacterium that undergoes phenotypic variation and can have both
      pathogenic and mutualistic roles. Through extensive gene deletion, pathway
      targeted molecular networking, quantitative proteomic analysis, and NMR, we show
      that the genetic locus affects the regulation of quorum sensing and secondary
      metabolic enzymes and encodes new pteridine metabolites functionalized with cis
      amide acyl-side chains, termed pepteridine A (1) and B (2). The pepteridines are
      produced in the pathogenic phenotypic variant and represent the first reported
      metabolites to be synthesized by a hybrid NRPS-pteridine pathway. These studies
      expand our view of the combinatorial biosynthetic potential available in
      bacteria.

PMID- 28431214
TI  - Interferon-gamma Released by Activated CD8+ T Lymphocytes Impairs the Calcium
      Resorption Potential of Osteoclasts in Calcified Human Aortic Valves.
AB  - In calcific aortic valve disease (CAVD), activated T lymphocytes localize with
      osteoclast regions; however, the functional consequences of this association
      remain unknown. We hypothesized that CD8+ T cells modulate calcification in CAVD.
      CAVD valves (n = 52) dissected into noncalcified and calcified portions were
      subjected to mRNA extraction, real-time quantitative PCR, enzyme-linked
      immunosorbent assay, and immunohistochemical analyses. Compared with noncalcified
      portions, calcified regions exhibited elevated transcripts for CD8, interferon
      (IFN)-gamma, CXCL9, Perforin 1, Granzyme B, and heat shock protein 60. Osteoclast
      associated receptor activator of NK-kappaB ligand (RANKL), tartrate-resistant
      acid phosphatase (TRAP), and osteoclast-associated receptor increased
      significantly. The stimulation of tissue with phorbol-12-myristate-13-acetate and
      ionomycin, recapitulating CAVD microenvironment, resulted in IFN-gamma release.
      Real-time quantitative PCR detected mRNAs for CD8+ T-cell activation (Perforin 1,
      Granzyme B). In stimulated versus unstimulated organoid cultures, elevated IFN
      gamma reduced the mRNAs encoding for RANKL, TRAP, and Cathepsin K. Molecular
      imaging showed increased calcium signal intensity in stimulated versus
      unstimulated parts. CD14+ monocytes treated either with recombinant human IFN
      gamma or with conditioned media-derived IFN-gamma exhibited low levels of
      Cathepsin K, TRAP, RANK, and tumor necrosis factor receptor-associated factor 6
      mRNAs, whereas concentrations of the T-cell co-activators CD80 and CD86 increased
      in parallel with reduced osteoclast resorptive function, effects abrogated by
      neutralizing anti-IFN-gamma antibodies. CD8+ cell-derived IFN-gamma suppresses
      osteoclast function and may thus favor calcification in CAVD.

PMID- 28431215
TI  - Early treatment improves urodynamic prognosis in neurogenic voiding dysfunction:
      20 years of experience.
AB  - OBJECTIVE: To evaluate the association between early treatment and urodynamic
      improvement in pediatric and adolescent patients with neurogenic bladder.
      METHODOLOGY: Retrospective longitudinal and observational study (between 1990 and
      2013) including patients with neurogenic bladder and myelomeningocele treated
      based on urodynamic results. The authors evaluated the urodynamic follow-up
      (bladder compliance and maximum bladder capacity and pressure) considering the
      first urodynamic improvement in two years as the outcome variable and early
      referral as the exposure variable, using a descriptive and multivariate analysis
      with logistic regression model. RESULTS: Among 230 patients included, 52% had an
      early referral. The majority were diagnosed as overactive bladder with high
      bladder pressure (>=40cm H2O) and low bladder compliance (3mL/cmH2O) and were
      treated with oxybutynin and intermittent catheterization. Urodynamic follow-up
      results showed 68% of improvement at the second urodynamic examination decreasing
      bladder pressure and increasing bladder capacity and compliance. The percentage
      of incontinence and urinary tract infections decreased over treatment. Early
      referral (one-year old or less) increased by 3.5 the probability of urodynamic
      improvement in two years (95% CI: 1.81-6.77). CONCLUSION: Treatment onset within
      the first year of life improves urodynamic prognosis in patients with neurogenic
      bladder and triplicates the probability of urodynamic improvement in two years.
      The role of neonatologists and pediatricians in early referral is extremely
      important.

PMID- 28431216
TI  - Synthesis and loading-dependent characteristics of nitrogen-doped graphene
      foam/carbon nanotube/manganese oxide ternary composite electrodes for high
      performance supercapacitors.
AB  - The ternary composite electrodes, nitrogen-doped graphene foam/carbon
      nanotube/manganese dioxide (NGF/CNT/MnO2), have been successfully fabricated via
      chemical vapor deposition (CVD) and facile hydrothermal method. The morphologies
      of the MnO2 nanoflakes presented the loading-dependent characteristics and the
      nanoflake thickness could also be tuned by MnO2 mass loading in the fabrication
      process. The correlation between their morphology and electrochemical performance
      was systematically investigated by controlling MnO2 mass loading in the ternary
      composite electrodes. The electrochemical properties of the flexible ternary
      electrode (MnO2 mass loading of 70%) exhibited a high areal capacitance of
      3.03F/cm2 and a high specific capacitance of 284F/g at the scan rate of 2mV/s.
      Moreover, it was interesting to find that the capacitance of the NGF/CNT/MnO2
      composite electrodes showed a 51.6% increase after 15,000 cycles. The gradual
      increase in specific capacitance was due to the formation of defective regions in
      the MnO2 nanostructures during the electrochemical cycles of the electrodes,
      which further resulted in increased porosity, surface area, and consequently
      increased electrochemical capacity. This work demonstrates a rarely reported
      conclusion about loading-dependent characteristics for the NGF/CNT/MnO2 ternary
      composite electrodes. It will bring new perspectives on designing novel ternary
      or multi-structure for various energy storage applications.

PMID- 28431217
TI  - Reduced graphene oxide as an effective adsorbent for removal of malachite green
      dye: Plausible adsorption pathways.
AB  - Efficient removal of malachite green (MG) dye from simulated wastewater is
      demonstrated using high surface area reduced graphene oxide (rGO). The plausible
      interaction pathways between MG dye and rGO are deduced from nanostructural
      features (HRTEM) of rGO and spectroscopic analyses (FTIR and Raman). The high
      surface area (931m2?gm-1) of rGO, pi-pi interaction between the aromatic rings of
      MG dye and graphitic skeleton, and electrostatic interaction of cationic centre
      of MG dye with pi-electron clouds and negatively charged residual oxygen
      functionalities of rGO collectively facilitate the adsorption of MG dye on the
      rGO. The rGO displays adsorption capacity as high as 476.2mg?g-1 for MG dye. The
      thermodynamic parameters calculated from the temperature dependent isotherms
      suggested that the adsorption was a spontaneous and endothermic process. These
      results promise the potential of high surface area rGO for efficient removal of
      cationic dyes for wastewater treatment.

PMID- 28431218
TI  - Letter to the Editor re: Nexus of Cancer & Alzheimer's.

PMID- 28431221
TI  - A Shout Out to Chemical Biology, a Multidisciplinary Field Par Excellence.

PMID- 28431219
TI  - Genetic analysis of alpha-synuclein 3' untranslated region and its corresponding
      microRNAs in relation to Parkinson's disease compared to dementia with Lewy
      bodies.
AB  - INTRODUCTION: The alpha-synuclein (SNCA) gene has been implicated in the etiology
      of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: A
      computational analysis of SNCA 3' untranslated region to identify potential
      microRNA (miRNA) binding sites and quantitative real-time polymerase chain
      reaction (PCR) to determine their expression in isogenic induced pluripotent stem
      cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB,
      respectively, were performed. In addition, we performed a deep sequencing
      analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD,
      DLB, and normal controls, followed by genetic association analysis of the
      identified variants. RESULTS: We identified four miRNA binding sites and observed
      a neuronal-type-specific expression profile for each miRNA in the different
      isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic
      neurons. Furthermore, we found that the short structural variant rs777296100
      polyT was moderately associated with DLB but not with PD. DISCUSSION: We suggest
      that the regulation of SNCA expression through miRNAs is neuronal-type-specific
      and possibly plays a part in the phenotypic heterogeneity of synucleinopathies.
      Furthermore, genetic variability in the SNCA gene may contribute to
      synucleinopathies in a pathology-specific manner.

PMID- 28431220
TI  - Contribution of ankle-foot orthosis moment in regulating ankle and knee motions
      during gait in individuals post-stroke.
AB  - BACKGROUND: Ankle-foot orthosis moment resisting plantarflexion has systematic
      effects on ankle and knee joint motion in individuals post-stroke. However, it is
      not known how much ankle-foot orthosis moment is generated to regulate their
      motion. The aim of this study was to quantify the contribution of an articulated
      ankle-foot orthosis moment to regulate ankle and knee joint motion during gait in
      individuals post-stroke. METHODS: Gait data were collected from 10 individuals
      post-stroke using a Bertec split-belt instrumented treadmill and a Vicon 3
      dimensional motion analysis system. Each participant wore an articulated ankle
      foot orthosis whose moment resisting plantarflexion was adjustable at four
      levels. Ankle-foot orthosis moment while walking was calculated under the four
      levels based on angle-moment relationship of the ankle-foot orthosis around the
      ankle joint measured by bench testing. The ankle-foot orthosis moment and the
      joint angular position (ankle and knee) relationship in a gait cycle was plotted
      to quantify the ankle-foot orthosis moment needed to regulate the joint motion.
      FINDINGS: Ankle and knee joint motion were regulated according to the amount of
      ankle-foot orthosis moment during gait. The ankle-foot orthosis maintained the
      ankle angular position in dorsiflexion and knee angular position in flexion
      throughout a gait cycle when it generated moment from -0.029 (0.011) to -0.062
      (0.019) Nm/kg (moment resisting plantarflexion was defined as negative).
      INTERPRETATIONS: Quantifying the contribution of ankle-foot orthosis moment
      needed to regulate lower limb joints within a specific range of motion could
      provide valuable criteria to design an ankle-foot orthosis for individuals post
      stroke.

PMID- 28431222
TI  - Principles of Chemical Biology: From MAGIC to Gut Fungi, via "Plug-And-Play"
      Biosensors.
AB  - This month: New MAGIC linking mitochondrial biology and proteostasis, split RNA
      polymerase based biosensors, and a role that fungi play in human gut microbiome.

PMID- 28431223
TI  - PINK1-Based Screen Shines Light on Autophagy Enhancers for Parkinson's Disease.
AB  - In this issue of Cell Chemical Biology, Zhang et al. (2017) report a zebrafish
      model of Parkinson's disease (PD), incorporating the PD-protein PINK1 and
      rotenone, a toxin linked to PD. Using it as a drug-screening platform, they
      identify trifluoperazine and other piperazine phenothiazines as protective
      compounds that enhance autophagy independent of PINK1.

PMID- 28431224
TI  - ADP-Ribosylation Goes Normal: Serine as the Major Site of the Modification.
AB  - Proteins containing adenosine diphosphate ribosylserine as a posttranslational
      modification are widespread and formed via HPF1-assisted, PARP-1-mediated
      PARylation as Bonfiglio et al. (2017) report in a recent issue of Molecular Cell.

PMID- 28431225
TI  - Retraction Notice to: Targeting Mycobacterial Enzymes with Natural Products.

PMID- 28431226
TI  - The impact of automatic devices for capillary blood collection on efficiency and
      pain response in newborns: A randomized controlled trial.
AB  - BACKGROUND: The heel stick is the method of choice in most neonatal units for
      capillary blood sampling, and it represents the most common event among all
      painful procedures performed on newborns. The type and design of heel stick
      device and the clinical procedure to collect a blood sample may have an impact on
      newborn pain response as well. OBJECTIVE: To compare the pain response and
      efficiency of different automated devices for capillary blood collection in
      newborns. DESIGN: Randomized clinical trial. SETTING: Postnatal ward of a
      tertiary-care university hospital in Italy. PARTICIPANTS: Newborn infants at
      gestational age >=34 weeks undergoing the metabolic screening test after the 49th
      hour of life. METHODS: A total of 762 neonates were recruited and randomized into
      6 groups (127 babies in each group) assigned to 6 different capillary blood
      collection devices (Ames MiniletTM Lancet; Cardinal Health Gentleheel(r); Natus
      Medical NeatNickTM; BD QuikheelTM Lancet; Vitrex Steriheel(r) Baby Lancet;
      Accriva Diagnostics Tenderfoot(r)). MAIN OUTCOME MEASURES: The following data
      were collected and assessed for each of the 6 groups evaluated: a) number of heel
      sticks, b) pain score according to the Neonatal Infant Pain Scale (NIPS) and c)
      need to squeeze the heel. RESULTS: The Ames MiniletTM Lancet device was found to
      perform by far the worst compared to the five device underexamination: it
      required the highest number of sticks (mean=3.91; 95% CI: 3.46-4.36), evoked the
      most intense pain (mean=3.98; 95% CI: 3.77-4.20), and most frequently
      necessitated squeezing the heel (92.9%; 95% CI: 86.9-96.3). The five devices
      under examination appeared to be similar in terms of the number of sticks
      required, but differed slightly in NIPS score and in need to squeeze the heel.
      CONCLUSION: The Accriva Diagnostics Tenderfoot(r) device demonstrated the
      greatest efficiency for blood sampling and evoked the least pain. With this
      device, the metabolic screening test could be performed with a single skin
      incision in the large majority of infants (98.4%), heel squeezing was limited to
      only 6.3% of infants, and the NIPS score turns out to be lower than other devices
      in our study (1.22; 95% CI 1.05-1.39).

PMID- 28431227
TI  - Membrane Lipids Speak to Histones.
AB  - In this issue of Molecular Cell, Ye et al. (2017) use a combination of genetic,
      metabolomic, and transcriptomic approaches to explore the potential for
      methionine metabolism to influence signal transduction and gene expression in
      budding yeast.

PMID- 28431228
TI  - A Determined "Hesitation" on H3K27me3 Empowers Stem Cells to Differentiate.
AB  - To uncover the precise mechanisms coordinating proliferation and fate choice of
      stem cells, in this issue of Molecular Cell and in an accompanying paper in Cell
      Reports, Mazo and colleagues (Petruk et al. 2017a, 2017b) reveal that delayed
      accumulation of H3K27me3 on nascent DNA is essential to recruit pioneer
      transcription factors in stem cell differentiation.

PMID- 28431229
TI  - Functional Enhancer Screening in Single Cells.
AB  - In this issue of Molecular Cell, Xie et al. (2017) introduce Mosaic-seq, a
      powerful technology that combines CRISPRi and single-cell RNA-seq. This method
      enables the high-throughput assessment of contributions of enhancers to gene
      regulation.

PMID- 28431230
TI  - Structural Basis for Guide RNA Processing and Seed-Dependent DNA Targeting by
      CRISPR-Cas12a.
AB  - The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome
      editing, possesses two distinct nuclease activities: endoribonuclease activity
      for processing its own guide RNAs and RNA-guided DNase activity for target DNA
      cleavage. To elucidate the molecular basis of both activities, we determined
      crystal structures of Francisella novicida Cas12a bound to guide RNA and in
      complex with an R-loop formed by a non-cleavable guide RNA precursor and a full
      length target DNA. Corroborated by biochemical experiments, these structures
      reveal the mechanisms of guide RNA processing and pre-ordering of the seed
      sequence in the guide RNA that primes Cas12a for target DNA binding. Furthermore,
      the R-loop complex structure reveals the strand displacement mechanism that
      facilitates guide-target hybridization and suggests a mechanism for double
      stranded DNA cleavage involving a single active site. Together, these insights
      advance our mechanistic understanding of Cas12a enzymes and may contribute to
      further development of genome editing technologies.

PMID- 28431232
TI  - Genome-wide Mapping of DROSHA Cleavage Sites on Primary MicroRNAs and
      Noncanonical Substrates.
AB  - MicroRNA (miRNA) maturation is initiated by DROSHA, a double-stranded RNA (dsRNA)
      specific RNase III enzyme. By cleaving primary miRNAs (pri-miRNAs) at specific
      positions, DROSHA serves as a main determinant of miRNA sequences and a highly
      selective gatekeeper for the canonical miRNA pathway. However, the sites of
      DROSHA-mediated processing have not been annotated, and it remains unclear to
      what extent DROSHA functions outside the miRNA pathway. Here, we establish a
      protocol termed "formaldehyde crosslinking, immunoprecipitation, and sequencing
      (fCLIP-seq)," which allows identification of DROSHA cleavage sites at single
      nucleotide resolution. fCLIP identifies numerous processing sites, suggesting
      widespread end modifications during miRNA maturation. fCLIP also finds many pri
      miRNAs that undergo alternative processing, yielding multiple miRNA isoforms.
      Moreover, we discovered dozens of DROSHA substrates on non-miRNA loci, which may
      serve as cis-elements for DROSHA-mediated gene regulation. We anticipate that
      fCLIP-seq could be a general tool for investigating interactions between dsRNA
      binding proteins and structured RNAs.

PMID- 28431231
TI  - Sequestration from Protease Adaptor Confers Differential Stability to Protease
      Substrate.
AB  - According to the N-end rule, the N-terminal residue of a protein determines its
      stability. In bacteria, the adaptor ClpS mediates proteolysis by delivering
      substrates bearing specific N-terminal residues to the protease ClpAP. We now
      report that the Salmonella adaptor ClpS binds to the N terminus of the regulatory
      protein PhoP, resulting in PhoP degradation by ClpAP. We establish that the PhoP
      activated protein MgtC protects PhoP from degradation by outcompeting ClpS for
      binding to PhoP. MgtC appears to act exclusively on PhoP, as it did not alter the
      stability of a different ClpS-dependent ClpAP substrate. Removal of five N
      terminal residues rendered PhoP stability independent of both the clpS and mgtC
      genes. By preserving PhoP protein levels, MgtC enables normal temporal
      transcription of PhoP-activated genes. The identified mechanism provides a simple
      means to spare specific substrates from an adaptor-dependent protease.

PMID- 28431234
TI  - TPP1 Blocks an ATR-Mediated Resection Mechanism at Telomeres.

PMID- 28431233
TI  - A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis.
AB  - During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem
      loop-structured precursors into mature miRNAs. These processing steps can be
      posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have
      used a proteomics-based pull-down approach to map and characterize the
      interactome of a multitude of pre-miRNAs. We identify ~180 RBPs that interact
      specifically with distinct pre-miRNAs. For functional validation, we combined
      RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent
      changes in miRNA levels. Indeed, a large number of the investigated candidates,
      including splicing factors and other mRNA processing proteins, have effects on
      miRNA processing. As an example, we show that TRIM71/LIN41 is a potent regulator
      of miR-29a processing and its inactivation directly affects miR-29a targets. We
      provide an extended database of RBPs that interact with pre-miRNAs in extracts of
      different cell types, highlighting a widespread layer of co- and
      posttranscriptional regulation of miRNA biogenesis.

PMID- 28431235
TI  - Improving Surgeons' Comfort With Prismatic Glasses During Cleft Palate Surgery:
      Preliminary Findings.
AB  - PURPOSE: We aimed to observe the effect of prismatic glasses on improving
      surgeons' comfort during cleft palate surgery. MATERIALS AND METHODS: A within
      subjects design was used. We included 3 oral-maxillofacial surgeons and 6
      patients with complete cleft palate in the study. One group of cleft palate
      patients (3 complete cleft palates) was allocated to each of the 3 surgeons not
      wearing prismatic glasses, and another similar group of cleft palate patients was
      allocated to the same 3 surgeons wearing prismatic glasses. The push-back method
      was performed in all cleft palate patients by all surgeons. The degree of neck
      flexion exhibited by all surgeons was digitally video recorded. Screen-capture
      images of the video recordings were collected, and neck flexion in all video
      recordings was analyzed. All surgeons completed a questionnaire based on a visual
      analog scale to assess their discomfort symptoms of the neck, shoulders, and
      back. Operative time and bleeding volume were recorded to assess operational
      efficiency. RESULTS: Use of prismatic glasses significantly reduced surgeons'
      working time spent in pronounced neck flexion during cleft palate surgery (P <
      .05), and there was a statistically significant reduction in the visual analog
      scale discomfort scores for the neck, back, and shoulders with the use of
      prismatic glasses (P < .05). However, no significant difference was found in
      operational time (P = .337) and bleeding volume (P = .183) attributable to the
      presence or absence of prismatic glasses. CONCLUSIONS: An ergonomic approach to
      cleft palate surgery in which surgeons wore prismatic glasses improved neck,
      back, and shoulder comfort.

PMID- 28431236
TI  - Unicystic Ameloblastoma Revisited: Comparison of Massachusetts General Hospital
      Outcomes With Original Robinson and Martinez Report.
AB  - PURPOSE: Robinson and Martinez established unicystic ameloblastoma (UA) as a
      distinct pathologic entity in 1977. Using their original description, the aims of
      this study were to compare the clinical presentation and outcomes of UA treated
      at Massachusetts General Hospital (MGH) with outcomes reported in the original
      article. PATIENTS AND METHODS: This was a retrospective cohort study of MGH
      patients treated for UA during a 15-year period. Patients were included if they
      had a confirmed clinical and histologic diagnosis of UA. The primary predictor
      variable was the source of the study sample (MGH vs Robinson and Martinez).
      Secondary variables included age, gender, radiographic appearance, treatment, and
      histologic subtype. The primary outcome variable was the number of recurrences
      over time comparing the 2 groups. RESULTS: There were 19 patients (10 female and
      9 male patients) in the MGH group and 20 patients (10 female and 10 male
      patients) in the Robinson and Martinez study. The lesions were predominantly
      unilocular (13 in MGH group and 19 in Robinson and Martinez group), located in
      the mandible (18 in MGH group and 20 in Robinson and Martinez group), and tooth
      associated (12 in MGH group and 14 in Robinson and Martinez group). No
      statistically significant demographic differences were noted between the 2
      groups. In the MGH group, 13 cases (68%) exhibited mural or intramural
      ameloblastic epithelium, 4 (21%) were luminal or intraluminal, and 2 were
      unknown. However, histologic configuration was not reported in the Robinson and
      Martinez group. MGH patients were treated by enucleation (n = 7, 37%) or
      resection (n = 12, 63%) compared with enucleation in 100% cases in the Robinson
      and Martinez group. Overall, the disease-free survival rate was higher in the
      Robinson and Martinez group, but the difference was not statistically significant
      (P = .089). Within the MGH group, 100% of recurrences occurred in patients with
      mural invasion treated by enucleation. CONCLUSIONS: The results of this study
      support UA as a distinct entity based on demographic, clinical, and radiographic
      criteria. Outcomes in the MGH group were influenced by the degree of ameloblastic
      epithelial invasion and suggest that this variable should be considered when
      planning treatment.

PMID- 28431237
TI  - Bringing Culture to Bacteria.

PMID- 28431238
TI  - Reducing Recurrence of C. difficile Infection.
AB  - Clostridium difficile infection (CDI) is facilitated by alteration of the
      microbiome following antibiotic administration. Antimicrobial therapy directed
      against the pathogen can treat CDI. Unfortunately, ~20% of successfully treated
      patients will suffer recurrence. Bezlotoxumab, a human monoclonal antibody, binds
      to C. difficile toxin B (TcdB), reducing recurrence presumably by limiting
      epithelial damage and facilitating microbiome recovery.

PMID- 28431239
TI  - Resident Macrophages: Near and Dear to Your Heart.
AB  - In this issue of Cell, Hulsmans et al. identify a subset of macrophages residing
      within the cardiac conduction system, which orchestrates cardiac rhythm.
      Macrophages directly couple with cardiomyocytes, and their perturbation alters
      cardiac conduction, suggesting that pharmacological manipulation of resident
      macrophages might represent a new strategy to combat cardiac arrhythmias.

PMID- 28431240
TI  - Building a Translational Microbiome Toolbox.
AB  - Designing successful microbiota-based therapies requires in-depth understanding
      of the ecological foundations of this community. In this issue, two studies by
      Whitaker et al. and Lim et al. provide refined genetic tools for dissecting the
      spatial organization and temporal dynamics of bacterial communities at the single
      cell and -gene levels.

PMID- 28431242
TI  - Structural and Functional Analysis of a beta2-Adrenergic Receptor Complex with
      GRK5.
AB  - The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by
      GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on
      arrestin-mediated signaling. While a structural understanding of GPCR/G-protein
      and GPCR/arrestin complexes has emerged in recent years, the molecular
      architecture of a GPCR/GRK complex remains poorly defined. We used a
      comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange
      mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics
      simulations, and computational docking to analyze GRK5 interaction with the beta2
      adrenergic receptor (beta2AR). These studies revealed a dynamic mechanism of
      complex formation that involves large conformational changes in the GRK5
      RH/catalytic domain interface upon receptor binding. These changes facilitate
      contacts between intracellular loops 2 and 3 and the C terminus of the beta2AR
      with the GRK5 RH bundle subdomain, membrane-binding surface, and kinase catalytic
      cleft, respectively. These studies significantly contribute to our understanding
      of the mechanism by which GRKs regulate the function of activated GPCRs.
      PAPERCLIP.

PMID- 28431243
TI  - Cryo-EM Structure of the Open Human Ether-a-go-go-Related K+ Channel hERG.
AB  - The human ether-a-go-go-related potassium channel (hERG, Kv11.1) is a voltage
      dependent channel known for its role in repolarizing the cardiac action
      potential. hERG alteration by mutation or pharmacological inhibition produces
      Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. We have
      determined the molecular structure of hERG to 3.8 A using cryo-electron
      microscopy. In this structure, the voltage sensors adopt a depolarized
      conformation, and the pore is open. The central cavity has an atypically small
      central volume surrounded by four deep hydrophobic pockets, which may explain
      hERG's unusual sensitivity to many drugs. A subtle structural feature of the hERG
      selectivity filter might correlate with its fast inactivation rate, which is key
      to hERG's role in cardiac action potential repolarization.

PMID- 28431241
TI  - AKT/PKB Signaling: Navigating the Network.
AB  - The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered
      25 years ago and has been the focus of tens of thousands of studies in diverse
      fields of biology and medicine. There have been many advances in our knowledge of
      the upstream regulatory inputs into AKT, key multifunctional downstream signaling
      nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of
      AKT, and the complex circuitry of this dynamically branching and looping
      signaling network that is ubiquitous to nearly every cell in our body. Mouse and
      human genetic studies have also revealed physiological roles for the AKT network
      in nearly every organ system. Our comprehension of AKT regulation and functions
      is particularly important given the consequences of AKT dysfunction in diverse
      pathological settings, including developmental and overgrowth syndromes, cancer,
      cardiovascular disease, insulin resistance and type 2 diabetes, inflammatory and
      autoimmune disorders, and neurological disorders. There has also been much
      progress in developing AKT-selective small molecule inhibitors. Improved
      understanding of the molecular wiring of the AKT signaling network continues to
      make an impact that cuts across most disciplines of the biomedical sciences.

PMID- 28431244
TI  - Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics.
AB  - The human microbiota greatly affects physiology and disease; however, the
      contribution of bacteria to the response to chemotherapeutic drugs remains poorly
      understood. Caenorhabditis elegans and its bacterial diet provide a powerful
      system to study host-bacteria interactions. Here, we use this system to study how
      bacteria affect the C. elegans response to chemotherapeutics. We find that
      different bacterial species can increase the response to one drug yet decrease
      the effect of another. We perform genetic screens in two bacterial species using
      three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine
      (FUDR), and camptothecin (CPT). We find numerous bacterial nucleotide metabolism
      genes that affect drug efficacy in C. elegans. Surprisingly, we find that 5-FU
      and FUDR act through bacterial ribonucleotide metabolism to elicit their
      cytotoxic effects in C. elegans rather than by thymineless death or DNA damage.
      Our study provides a blueprint for characterizing the role of bacteria in the
      host response to chemotherapeutics.

PMID- 28431245
TI  - Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans.
AB  - Fluoropyrimidines are the first-line treatment for colorectal cancer, but their
      efficacy is highly variable between patients. We queried whether gut microbes, a
      known source of inter-individual variability, impacted drug efficacy. Combining
      two tractable genetic models, the bacterium E. coli and the nematode C. elegans,
      we performed three-way high-throughput screens that unraveled the complexity
      underlying host-microbe-drug interactions. We report that microbes can bolster or
      suppress the effects of fluoropyrimidines through metabolic drug interconversion
      involving bacterial vitamin B6, B9, and ribonucleotide metabolism. Also,
      disturbances in bacterial deoxynucleotide pools amplify 5-FU-induced autophagy
      and cell death in host cells, an effect regulated by the nucleoside diphosphate
      kinase ndk-1. Our data suggest a two-way bacterial mediation of fluoropyrimidine
      effects on host metabolism, which contributes to drug efficacy. These findings
      highlight the potential therapeutic power of manipulating intestinal microbiota
      to ensure host metabolic health and treat disease.

PMID- 28431246
TI  - Fatty Acids Regulate Germline Sex Determination through ACS-4-Dependent
      Myristoylation.
AB  - Fat metabolism has been linked to fertility and reproductive adaptation in
      animals and humans, and environmental sex determination potentially plays a role
      in the process. To investigate the impact of fatty acids (FA) on sex
      determination and reproductive development, we examined and observed an impact of
      FA synthesis and mobilization by lipolysis in somatic tissues on oocyte fate in
      Caenorhabditis elegans. The subsequent genetic analysis identified ACS-4, an acyl
      CoA synthetase and its FA-CoA product, as key germline factors that mediate the
      role of FA in promoting oocyte fate through protein myristoylation. Further tests
      indicated that ACS-4-dependent protein myristoylation perceives and translates
      the FA level into regulatory cues that modulate the activities of MPK-1/MAPK and
      key factors in the germline sex-determination pathway. These findings, including
      a similar role of ACS-4 in a male/female species, uncover a likely conserved
      mechanism by which FA, an environmental factor, regulates sex determination and
      reproductive development.

PMID- 28431247
TI  - The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of
      Insulin Receptor Turnover.
AB  - Aging is attended by a progressive decline in protein homeostasis (proteostasis),
      aggravating the risk for protein aggregation diseases. To understand the
      coordination between proteome imbalance and longevity, we addressed the
      mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key
      regulator of proteostasis. We observed that CHIP deficiency leads to increased
      levels of the insulin receptor (INSR) and reduced lifespan of worms and flies.
      The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway
      and thereby defines metabolism and aging. INSR is a direct target of CHIP, which
      triggers receptor monoubiquitylation and endocytic-lysosomal turnover to promote
      longevity. However, upon proteotoxic stress conditions and during aging, CHIP is
      recruited toward disposal of misfolded proteins, reducing its capacity to degrade
      the INSR. Our study indicates a competitive relationship between proteostasis and
      longevity regulation through CHIP-assisted proteolysis, providing a mechanistic
      concept for understanding the impact of proteome imbalance on aging.

PMID- 28431248
TI  - Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease.
AB  - The environmentally widespread polysaccharide chitin is degraded and recycled by
      ubiquitous bacterial and fungal chitinases. Although vertebrates express active
      chitinases from evolutionarily conserved loci, their role in mammalian physiology
      is unclear. We show that distinct lung epithelial cells secrete acidic mammalian
      chitinase (AMCase), which is required for airway chitinase activity. AMCase
      deficient mice exhibit premature morbidity and mortality, concomitant with
      accumulation of environmentally derived chitin polymers in the airways and
      expression of pro-fibrotic cytokines. Over time, these mice develop spontaneous
      pulmonary fibrosis, which is ameliorated by restoration of lung chitinase
      activity by genetic or therapeutic approaches. AMCase-deficient epithelial cells
      express fibrosis-associated gene sets linked with cell stress pathways. Mice with
      lung fibrosis due to telomere dysfunction and humans with interstitial lung
      disease also accumulate excess chitin polymers in their airways. These data
      suggest that altered chitin clearance could exacerbate fibrogenic pathways in the
      setting of lung diseases characterized by epithelial cell dysfunction.

PMID- 28431249
TI  - Macrophages Facilitate Electrical Conduction in the Heart.
AB  - Organ-specific functions of tissue-resident macrophages in the steady-state heart
      are unknown. Here, we show that cardiac macrophages facilitate electrical
      conduction through the distal atrioventricular node, where conducting cells
      densely intersperse with elongated macrophages expressing connexin 43. When
      coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap
      junctions, cardiac macrophages have a negative resting membrane potential and
      depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the
      resting membrane potential of cardiomyocytes more positive and, according to
      computational modeling, accelerate their repolarization. Photostimulation of
      channelrhodopsin-2-expressing macrophages improves atrioventricular conduction,
      whereas conditional deletion of connexin 43 in macrophages and congenital lack of
      macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage
      ablation induces progressive atrioventricular block. These observations implicate
      macrophages in normal and aberrant cardiac conduction.

PMID- 28431250
TI  - Nuclear Proximity of Mtr4 to RNA Exosome Restricts DNA Mutational Asymmetry.
AB  - The distribution of sense and antisense strand DNA mutations on transcribed
      duplex DNA contributes to the development of immune and neural systems along with
      the progression of cancer. Because developmentally matured B cells undergo
      biologically programmed strand-specific DNA mutagenesis at focal DNA/RNA hybrid
      structures, they make a convenient system to investigate strand-specific
      mutagenesis mechanisms. We demonstrate that the sense and antisense strand DNA
      mutagenesis at the immunoglobulin heavy chain locus and some other regions of the
      B cell genome depends upon localized RNA processing protein complex formation in
      the nucleus. Both the physical proximity and coupled activities of RNA helicase
      Mtr4 (and senataxin) with the noncoding RNA processing function of RNA exosome
      determine the strand-specific distribution of DNA mutations. Our study suggests
      that strand-specific DNA mutagenesis-associated mechanisms will play major roles
      in other undiscovered aspects of organismic development.

PMID- 28431251
TI  - Tunable Expression Tools Enable Single-Cell Strain Distinction in the Gut
      Microbiome.
AB  - Applying synthetic biology to engineer gut-resident microbes provides new avenues
      to investigate microbe-host interactions, perform diagnostics, and deliver
      therapeutics. Here, we describe a platform for engineering Bacteroides, the most
      abundant genus in the Western microbiota, which includes a process for high
      throughput strain modification. We have identified a novel phage promoter and
      translational tuning strategy and achieved an unprecedented level of expression
      that enables imaging of fluorescent-protein-expressing Bacteroides stably
      colonizing the mouse gut. A detailed characterization of the phage promoter has
      provided a set of constitutive promoters that span over four logs of strength
      without detectable fitness burden within the gut over 14 days. These promoters
      function predictably over a 1,000,000-fold expression range in phylogenetically
      diverse Bacteroides species. With these promoters, unique fluorescent signatures
      were encoded to allow differentiation of six species within the gut. Fluorescent
      protein-based differentiation of isogenic strains revealed that priority of gut
      colonization determines colonic crypt occupancy.

PMID- 28431253
TI  - CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes.

PMID- 28431252
TI  - Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the
      Gut.
AB  - The gut microbiota is implicated in numerous aspects of health and disease, but
      dissecting these connections is challenging because genetic tools for gut
      anaerobes are limited. Inducible promoters are particularly valuable tools
      because these platforms allow real-time analysis of the contribution of
      microbiome gene products to community assembly, host physiology, and disease. We
      developed a panel of tunable expression platforms for the prominent genus
      Bacteroides in which gene expression is controlled by a synthetic inducer. In the
      absence of inducer, promoter activity is fully repressed; addition of inducer
      rapidly increases gene expression by four to five orders of magnitude. Because
      the inducer is absent in mice and their diets, Bacteroides gene expression inside
      the gut can be modulated by providing the inducer in drinking water. We use this
      system to measure the dynamic relationship between commensal sialidase activity
      and liberation of mucosal sialic acid, a receptor and nutrient for pathogens.
      VIDEO ABSTRACT.

PMID- 28431254
TI  - Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding.

PMID- 28431256
TI  - Neurodevelopmental outcomes of neonates undergoing surgery under general
      anesthesia for malrotation of intestines.
AB  - BACKGROUND: It is difficult to differentiate between the potential adverse
      effects of general anesthesia (GA) on the developing brain and the role of
      associated co-morbidities and syndromes that can adversely affect
      neurodevelopmental outcomes in neonates undergoing GA. Neonates with malrotation
      of the intestines without volvulus usually do not have co-morbidities or
      syndromes. In addition, majority of them recover very well after surgery and are
      discharged home within a few days. Neonates with malrotation are a clean cohort
      of babies to study the role of a single episode of GA on the developing brain.
      AIMS: The study aimed to evaluate the neurodevelopmental outcomes of neonates
      undergoing GA for malrotation surgery. STUDY DESIGN: Retrospective review of
      neonates born at gestational age of >=32weeks undergoing laparotomy for
      malrotation. OUTCOME MEASURES: Neurodevelopment in the study cohort at the age of
      one year. RESULTS: 33 eligible infants were identified from the departmental
      database. All 33 survived and were assessed using the Griffiths Mental
      Development Scales (GMDS) at one year. Mean general quotient (GQ) of the study
      population was 98 (SD 7.33) which was similar to the population norms (100.2, SD
      12.8); p value 0.10. None of the infants developed cerebral palsy, tone
      abnormality, sensorineural deafness or blindness. There was no significant
      difference in the centiles at birth versus one year for weight and length (p
      values 0.454 and 0.178 respectively). Reassuringly, the head circumference
      centiles at one year showed a trend towards higher values (p value: 0.0735).
      CONCLUSION: One year developmental outcomes of neonates undergoing surgery under
      GA for malrotation were similar to population norms.

PMID- 28431255
TI  - Do orally-directed behaviors mediate the relationship between behavioral state
      and nutritive sucking in preterm infants?

PMID- 28431257
TI  - Integrated antimicrobial and antifouling ultrafiltration membrane by surface
      grafting PEO and N-chloramine functional groups.
AB  - Ultrafiltration membranes with integrated antimicrobial and antifouling
      properties were fabricated using an engineering thermoplastic (carboxylated
      cardopoly(aryl ether ketone, PEK-COOH). Different molecular weights of PEO (Mw:
      120, 350, 550) were grafted to the PEK-COOH membrane surface via EDC/NHS
      methodology. N-chloramine modified membranes then were prepared by simple
      exposure to dilute sodium hypochlorite solution. The surface grafting processes
      were all performed in water (i.e. without organic solvent). With this surface
      modification, the hydrophilicity of membranes improved significantly and the pure
      water flux increased compared to the unmodified PEK-COOH membrane. Furthermore,
      the PEO and N-chloramine modified membranes were resistant not only to both
      protein adsorption and bacterial adhesion, but also to microbial proliferation.
      The results of this work suggest that PEO and N-chloramine modified membranes are
      promising as fouling-resistant membranes.

PMID- 28431258
TI  - Cage and linear structured polysiloxane/epoxy hybrids for coatings: Surface
      property and film permeability.
AB  - Three polysiloxane/epoxy hybrids obtained by evolving cage- or linear-structured
      polysiloxane into poly glycidyl methacrylate (PGMA) matrix are compared used as
      coatings. One is the cage-structured hybrid of P(GMA/MA-POSS) copolymer obtained
      by GMA and methacrylisobutyl polyhedral oligomeric silsesquioxane (MA-POSS) via
      free radical polymerization, the other two are PGMA/NH2-POSS and PGMA/NH2-PDMS
      hybrids by cage-structured aminopropyllsobutyl POSS (NH2-POSS) or linear
      structured diamino terminated poly(dimethylsiloxane) (NH2-PDMS) to cure PGMA. The
      effect of MA-POSS, NH2-POSS and NH2-PDMS on polysiloxane/epoxy hybrid films is
      characterized according to their surface morphology, transparency, permeability,
      adhesive strength and thermo-mechanical properties. Due to caged POSS tending to
      agglomerate onto the film surface, P(GMA/MA-POSS) and PGMA/NH2-POSS films exhibit
      much more heterogeneous surfaces than PGMA/NH2-PDMS film, but the well
      compatibility between epoxy matrix and MA-POSS has provided P(GMA/MA-POSS) film
      with much higher transmittance (98%) than PGMA/NH2-POSS film (24%), PGMA/NH2-PDMS
      film (27%) and traditional epoxy resin film (5%). The introduction of
      polysiloxane into epoxy matrix is confirmed to create hybrids with strong
      adhesive strength (526-1113N) and high thermos-stability (Tg=262-282 degrees C),
      especially the cage-structured P(GMA/MA-POSS) hybrid (1113N and 282 degrees C),
      but the flexible PDMS improves PGMA/NH2-PDMS hybrid with much higher storage
      modulus (519MPa) than PGMA/NH2-POSS (271MPa), which suggests that PDMS is
      advantage in improving the film stiffness than POSS cages. However, cage
      structured P(GMA/MA-POSS) and PGMA/NH2-POSS indicate higher permeability than
      PGMA/NH2-PDMS and traditional epoxy resin. Comparatively, the cage-structured
      P(GMA/MA-POSS) hybrid is the best coating in transparency, permeability, adhesive
      strength and thermostability, but linear-structured PGMA/NH2-PDMS hybrid
      behaviors the best coating in mechanical property.

PMID- 28431259
TI  - Allosteric regulation of metabolism in cancer: endogenous mechanisms and
      considerations for drug design.
AB  - Alterations in metabolic processes have been linked to various diseases,
      including cancer. Although gene expression can dictate long-term metabolic
      adaptation, many metabolic changes found in cancer are associated with altered
      allosteric properties of the underlying enzymes. Small molecule-protein
      interactions and intracellular signalling converge to orchestrate these
      allosteric mechanisms, which, emerging evidence suggests, constitute a promising
      therapeutic avenue. In this review we focus on glucose and energy metabolism to
      illustrate the role of allostery in cancer physiology and we discuss approaches
      to streamline the process of targeting aberrant allosteric pathways with small
      molecules.

PMID- 28431260
TI  - Standardization of Brief Inventory of Social Support Exchange Network (BISSEN) in
      Japan.
AB  - This study describes the Brief Inventory of Social Support Exchange Network
      (BISSEN) as a standardized brief inventory measuring various aspects of social
      support. We confirmed the reliability and validity for function and direction of
      support and standardized the BISSEN. For Sample 1, a stratified random sampling
      method was used to select 5200 residents in Japan. We conducted mail surveys and
      responses were retrieved from 2274 participants (collection rate 43.7%).
      Participants completed a questionnaire packet that included BISSEN, suicidal
      ideation, depression, support seeking, and Multidimensional Scale of Perceived
      Social Support (MSPSS). Sample 2 surveys for test-retest reliability were
      conducted on 23 residents at approximately two-week intervals. Participants were
      asked about gender, age, and BISSEN. First, we assessed the internal consistency,
      test-retest reliability, construct, convergent, and concurrent validity.
      McDonald's omega (.73-.92) and test-retest correlations (.78-.85) demonstrated
      adequate internal consistency and test-retest reliability. Depression, support
      seeking, and MSPSS were significantly correlated with all scores of BISSEN. The
      non-suicidal ideation group had significantly more support compared to the
      suicidal ideation group. Therefore, function and direction of support in BISSEN
      had sufficient reliability and validity. Next, we standardized BISSEN using Z
      scores and percentile rank with respect to each 12 norm groups by age and gender.

PMID- 28431261
TI  - Dietary patterns and depression risk: A meta-analysis.
AB  - Although some studies have reported potential associations of dietary patterns
      with depression risk, a consistent perspective hasn't been estimated to date.
      Therefore, we conducted this meta-analysis to evaluate the relation between
      dietary patterns and the risk of depression. A literature research was conducted
      searching MEDLINE and EMBASE databases up to September 2016. In total, 21 studies
      from ten countries met the inclusion criteria and were included in the present
      meta-analysis. A dietary pattern characterized by a high intakes of fruit,
      vegetables, whole grain, fish, olive oil, low-fat dairy and antioxidants and low
      intakes of animal foods was apparently associated with a decreased risk of
      depression. A dietary pattern characterized by a high consumption of red and/or
      processed meat, refined grains, sweets, high-fat dairy products, butter, potatoes
      and high-fat gravy, and low intakes of fruits and vegetables is associated with
      an increased risk of depression. The results of this meta-analysis suggest that
      healthy pattern may decrease the risk of depression, whereas western-style may
      increase the risk of depression. However, more randomized controlled trails and
      cohort studies are urgently required to confirm this findings.

PMID- 28431263
TI  - Epigenetic therapy and chemosensitization in solid malignancy.
AB  - Epigenetic modifications result in dynamic shifts between transcriptionally
      active and suppressed states. The potentially reversible nature of epigenetic
      changes underlies the concept of epigenetic therapy, which serves to reprogram
      cancer cells as opposed to inducing cytotoxicity that occurs with standard
      chemotherapeutics. There are numerous enzymes involved in epigenetic changes and
      each can be potentially targetable. Although many investigations have evaluated
      the clinical potential of the various epigenetic therapies, currently only
      histone deacetylase inhibitors and DNA methyltransferase inhibitors are approved
      for use in specific hematologic malignancies. Use of epigenetic therapy
      coincident with cytotoxic or targeted systemic therapy appears to derive a
      benefit due to chemosensitization. Trials demonstrating efficacy from combination
      therapy have been performed in various diseases such as NSCLC, ovarian cancer and
      breast cancer. Furthermore, there are patient subsets in certain solid tumors in
      which epigenetic therapy provide durable response, such as patients with NSCLC
      and specific hypermethylation patterns. The encouraging results from combination
      therapy identified in these trials built upon prior investigations and have
      provided a foundation for ensuing trials seeking to evaluate epigenetic therapy.

PMID- 28431264
TI  - Intercomparison of methods to estimate black carbon emissions from cookstoves.
AB  - Black carbon is the second largest contributor to climate change and also poses
      risks to human health. Despite the need for black carbon (BC) emissions estimates
      from residential biomass burning for cooking, quantitative data are still scarce.
      This scarcity is mainly due to the scattered location of the stoves, as well as
      relatively costly and complex analytical methods available. Two low cost and easy
      to-use optical methods, a cell-phone based system and smoke stain reflectometry,
      where compared to elemental carbon (EC) concentrations by the Sunset OCEC
      Analyzer (TOT). The three techniques were challenged with different aerosol types
      (urban and biomass cookstoves), and different filter substrates (quartz and glass
      fibre). A good agreement was observed between the two low cost techniques and the
      reference system for the aerosol types and concentrations assessed, although the
      relationship was statistically different for each type of aerosol. The
      quantification of correction factors with respect to the reference method for the
      specific conditions under study is essential with either of the low-cost
      techniques. BC measurements from the cell-phone system and the reflectometer were
      moderately affected by the filter substrate. The easy use of the cell-phone based
      system may allow engaging cookstove users in the data collection process,
      increasing the amount and frequency of data collection which may, otherwise, not
      be feasible in resourced constrained locations. This would help to raise public
      awareness about environmental and health issues related to cookstoves.

PMID- 28431265
TI  - Nucleolar reorganization in response to rDNA damage.
AB  - Nucleoli, sites of ribosome biogenesis, form around nucleolar organizer regions
      (NORs) comprising rDNA arrays, located on human acrocentric chromosome p-arms.
      NORs provide an opportunity to investigate the DNA double strand break (DSB)
      response at highly transcribed, repetitive, essential loci. Targeted introduction
      of DSBs into rDNA results in ATM-dependent inhibition of RNA-polymerase I
      transcription, coupled with movement of rDNA from the nucleolar interior to
      anchoring points at the periphery. Reorganization renders rDNA accessible to
      repair factors, normally excluded from nucleoli. Importantly, rDNA DSBs recruit
      the accurate homologous recombination (HR) repair machinery throughout the cell
      cycle, suggesting that HR can be templated in cis. We discuss recent findings
      regarding the biophysical properties of nucleoli and suggest a mechanism for
      stress-induced nucleolar reorganization.

PMID- 28431262
TI  - Immunologic approaches for the treatment of multiple myeloma.
AB  - The FDA approval of two monoclonal antibodies in 2015has heralded a new era of
      targeted immunotherapies for multiple myeloma (MM). In this review we discuss the
      recent approaches using different immunological components to treat MM. In
      particular, we review current monoclonal antibody based therapies, engineered T-
      and NK cell products, 'off-target' immunomodulation, and strategies utilizing
      allogeneic cell transplantation in MM. We discuss how an immunologic approach
      offers promise for the treatment of this genetically heterogeneous disease, and
      how patients with acquired drug resistance may particularly benefit from these
      therapies. We also describe some of the limitations of the current strategies and
      speculate on the future of personalized immunotherapies for MM.

PMID- 28431266
TI  - Reduced abnormal integration of adult-generated granule cells does not attenuate
      spontaneous recurrent seizures in mice.
AB  - Epileptic seizures lead to aberrant hippocampal neurogenesis, including increased
      proliferation of neural progenitors and abnormal integrations of newly generated
      granule cells - hilar ectopic granule cells (EGCs), mossy fiber sprouting (MFS),
      and hilar basal dendrites (HBDs). Previous results from ablating hippocampal
      neurogenesis after acute seizures have been controversial with regards to the
      development of spontaneous recurrent seizures (SRSs). While ablation of
      hippocampal newborn cells was effective, a sufficient decrease of subsequent
      abnormal integrations in chronically epileptic hippocampus was not well
      established in these studies. Evaluations of the role of aberrant neurogenesis in
      epileptogenesis were therefore inconclusive. In this study, we ablated the
      hippocampal neurogenesis by methylazoxymethanol acetate (MAM) treatment both
      before and after pilocarpine induced status epilepticus (SE). We found that an
      overall ablation of newborn granule cells and a protracted delay after the cell
      ablation are required to eliminate subsequent abnormal integrations, including
      EGCs, MSF and HBDs. However, there were no alterations in frequency, duration and
      severity of chronic seizures were demonstrated following this regime. The current
      findings provide novel evidences that an overall decrease of abnormal
      integrations via cell ablation cannot exert significant effects on the
      development of SRSs at least in the model used in this study.

PMID- 28431267
TI  - miR-19 targeting of GSK3beta mediates sulforaphane suppression of lung cancer
      stem cells.
AB  - Cancer stem cells (CSCs) play a central role in the development of cancer. The
      canonical Wnt/beta-catenin pathway is critical for maintaining stemness of CSCs.
      Phytochemicals from dietary compounds possess anti-CSCs properties and have been
      characterized as promising therapeutic agents for the prevention and treatment of
      many cancers. To date, the involvement and function of miR-19, a key oncogenic
      miRNA, in regulating Wnt/beta-catenin pathway and lung CSCs has not been defined.
      Meanwhile, the effect of sulforaphane (SFN) on lung CSCs also remains to be
      elucidated. Here, we reported that lung CSCs up-regulated miR-19a and miR-19b
      expression. Overexpression of miR-19a/19b enhanced the ability of tumorsphere
      formation, up-regulated the expression of lung CSCs markers, increased Wnt/beta
      catenin pathway activation and beta-catenin/TCF transcriptional activity in lung
      CSCs. In contrary, down-regulation of miR-19 suppressed lung CSCs activity and
      Wnt/beta-catenin activation. We further revealed that miR-19 activated Wnt/beta
      catenin pathway by directly targeting GSK3beta, the key negative modulator of
      this pathway. Moreover, we showed that SFN exhibited inhibitory effect on lung
      CSCs through suppressing miR-19 and Wnt/beta-catenin pathway. Taken together,
      these data illustrate the role of miR-19 in regulating lung CSCs traits and miR
      19/GSK3beta/beta-catenin axis in SFN intervention of lung CSCs. Findings from
      this study could provide important new insights into the molecular mechanisms of
      lung CSCs regulation as well as its target intervention.

PMID- 28431268
TI  - Assessment of mutagenicity of water from Lake Sevan, Armenia with application of
      Tradescantia (clone 02).
AB  - For many decades water resources in Armenia have been affected by anthropogenic
      activity, therefore, a regular bioindication of genotoxic effects of the water
      bodies is desirable. The genotoxicity of water samples collected from different
      parts of Lake Sevan were assessed by means of Trad-SHM (stamen hair mutation)
      assay using Tradescantia (clone 02). Here we report a significant increase in the
      frequency of somatic mutations and morphological changes in the Tradescantia
      inflorescences exposed to the water samples compared to the control. The somatic
      mutations (recessive mutation and white mutation events) were mostly linked to
      the concentration of Al, Ni, As, Co and Pb in Artanish, Tsapatakh and
      Karchaghbyur, Noradus, Martuni and Litchk, while morphological changes (non
      surviving hairs) were related to Co level in Tsapatakh and Karchaghbyur. The
      results obtained show that Lake Sevan contains substances which may cause
      genotoxicity and teratogenicity in Tradescantia and probably also in aquatic
      animals. The results also show that Trad-SHM assay can be used for monitoring
      natural resources.

PMID- 28431269
TI  - Oxytocin in the postnatal period: Associations with attachment and maternal
      caregiving.
AB  - BACKGROUND: This study investigated the associations of maternal oxytocin, self
      reported attachment insecurity and depressive symptoms with maternal caregiving
      sensitivity at 3-4months postpartum, observed during the 'free play' and
      'reunion' episodes of the Still Face Procedure. METHODS: 112 mothers completed
      questionnaires and gave blood samples to determine oxytocin plasma levels before
      (time 1) and after participating in the Still Face Procedure with their infant
      (time 2). RESULTS: Sensitive maternal caregiving during the free play episode was
      predicted by 'good' infant behavior; during the reunion episode it was predicted
      by 'good' infant behavior, higher baseline levels of maternal oxytocin and a
      greater maternal oxytocin response, or in other words, a larger increase in
      maternal oxytocin level from time 1 to time 2. With other variables free to vary,
      baseline maternal oxytocin levels mediated an inverse relation between maternal
      adult attachment avoidance and sensitive maternal caregiving during the reunion
      episode. CONCLUSION: Results highlight the association between oxytocin and
      sensitive maternal caregiving and suggest that oxytocin is a biological mechanism
      through which maternal attachment insecurity affects early parenting quality.

PMID- 28431270
TI  - Clinicians' conflicting emotional responses to high suicide-risk patients
      Association with short-term suicide behaviors: A prospective pilot study.
AB  - BACKGROUND: Clinician's emotional responses to patients have been recognized as
      potentially relating to treatment outcome, however they have received little
      attention in the literature on suicide risk. We examine the relationship between
      a novel targeted measure of clinicians' emotional responses to high-risk
      psychiatric inpatients and their short-term post-discharge suicide behavior.
      METHODS: First-year psychiatry residents' emotional responses to their patients
      were assessed anonymously with the novel self-report 'Therapist Response
      Questionnaire-Suicide Form' (TRQ-SF). Patient outcomes were assessed at 1-2months
      post-discharge, and post-discharge suicide outcomes were assessed with the
      Columbia Suicide Severity Rating Scale. Following exploratory factor analysis of
      the TRQ-SF, scores on the resultant factors were examined for relationships with
      clinical and demographic measures and post-discharge suicide behavior. RESULTS: A
      two-factor model fit the data, with factors reflecting dimensions of
      affiliation/rejection and distress/non-distress. Two items that did not load
      robustly on either factor had face validity for hopefulness and hopelessness and
      were combined as a measure along a hopefulness/hopelessness dimension. The
      interaction Distress*Hopefulness, reflecting a conflicting emotional response
      pattern, significantly predicted post-discharge suicide outcomes even after
      covarying for depression, entrapment, and suicidal ideation severity. CONCLUSION:
      Clinicians' conflicting emotional responses to high-risk patients predicted
      subsequent suicidal behavior, independent of traditional risk factors. Our
      findings demonstrate the potential clinical value of assessing such responses.

PMID- 28431271
TI  - Investigation of pathology malpractice claims in China from 2002-2015.
AB  - OBJECTIVE: To examine pathology-related medical claims in China and identify the
      most common errors to result in such claims. METHOD: A retrospective analysis was
      performed of 71 forensic evaluation reports carried out in two Chinese institutes
      of forensic medicine between 2002 and 2015 due to suspicion of medical
      malpractice. The judicial outcomes of each case were also reviewed when
      available. RESULTS: Of 71 cases, 54 cases had judicial outcomes. The most
      frequently claimed events were false-negative diagnoses of skin cancer, invasive
      ductal carcinoma of the breast, and osteosarcoma; and false positive diagnoses of
      uterine cervical squamous cell carcinoma, gastric carcinoma, and soft tissue
      carcinoma. The most common cause of error (82%, 56 of 68) was pathological
      misinterpretation. Plaintiffs in most cases (89%, 48 of 54) received
      compensation. CONCLUSION: Our data are in agreement with other findings regarding
      the most frequent medical malpractice allegations related to pathology.
      Addressing the issues at the root of these claims would lead to a decline in the
      number of medical errors. Quality assurance programs and good pathologist
      clinician communication may decrease the risk of litigation.

PMID- 28431272
TI  - Specific microRNA-mRNA Regulatory Network of Colon Cancer Invasion Mediated by
      Tissue Kallikrein-Related Peptidase 6.
AB  - Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC)
      patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein
      subfamily of peptidase S1 family serine proteases, has been reported in CRC and
      is associated with low patient survival rates and poor disease prognosis. We
      knocked down KLK6 expression in HCT116 colon cancer cells to determine the
      significance of KLK6 expression for metastatic dissemination and to identify the
      KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer.
      KLK6 suppression resulted in decreased cells invasion in vitro with a minimal
      effect on the cell growth and viability. In vivo, animals with orthotopic colon
      tumors deficient in KLK6 expression had the statistically significant increase in
      survival rates (P=.005) and decrease in incidence of distant metastases. We
      further performed the integrated miRNA and messenger RNA (mRNA) expression
      profiling to identify functional miRNA-mRNA interactions associated with KLK6
      mediated invasiveness of colon cancer. Through bioinformatics analysis we
      identified and functionally validated the top two up-regulated miRNAs, miR-182
      and miR-203, and one down-regulated miRNA, miRNA-181d, and their seven mRNA
      effectors. The established miRNA-mRNA interactions modulate cellular
      proliferation, differentiation and epithelial-mesenchymal transition (EMT) in
      KLK6-expressing colon cancer cells via the TGF-beta signaling pathway and RAS
      related GTP-binding proteins. We confirmed the potential tumor suppressive
      properties of miR-181d and miR-203 in KLK6-expressing HCT116 cells using Matrigel
      invasion assay. Our data provide experimental evidence that KLK6 controls
      metastasis formation in colon cancer via specific downstream network of miRNA
      mRNA effectors.

PMID- 28431274
TI  - Distribution of Escherichia coli O157:H7 in ground beef: Assessing the clustering
      intensity for an industrial-scale grinder and a low and localized initial
      contamination.
AB  - Undercooked ground beef is regularly implicated in food-borne outbreaks involving
      pathogenic Shiga toxin-producing Escherichia coli. The dispersion of bacteria
      during mixing processes is of major concern for quantitative microbiological risk
      assessment since clustering will influence the number of bacteria the consumers
      might get exposed to as well as the performance of sampling plans used to detect
      contaminated ground beef batches. In this study, batches of 25kg of ground beef
      were manufactured according to a process mimicking an industrial-scale grinding
      with three successive steps: primary grinding, mixing and final grinding. The
      ground beef batches were made with 100% of chilled trims or with 2/3 of chilled
      trims and 1/3 of frozen trims. Prior grinding, one beef trim was contaminated
      with approximately 106-107CFU of E. coli O157:H7 on a surface of 0.5cm2 to reach
      a concentration of 10-100cells/g in ground beef. The E. coli O157:H7 distribution
      in ground beef was characterized by enumerating 60 samples (20 samples of 5g, 20
      samples of 25g and 20 samples of 100g) and fitting a Poisson-gamma model to
      describe the variability of bacterial counts. The shape parameter of the gamma
      distribution, also known as the dispersion parameter reflecting the amount of
      clustering, was estimated between 1.0 and 1.6. This k-value of approximately 1
      expresses a moderate level of clustering of bacterial cells in the ground beef.
      The impact of this clustering on the performance of sampling strategies was
      relatively limited in comparison to the classical hypothesis of a random
      repartition of pathogenic cells in mixed materials (purely Poisson distribution
      instead of Poisson-gamma distribution).

PMID- 28431273
TI  - Chromosomal Instability in Gastric Cancer Biology.
AB  - Gastric cancer (GC) is the fifth most common cancer in the world and accounts for
      7% of the total cancer incidence. The prognosis of GC is dismal in Western
      countries due to late diagnosis: approximately 70% of the patients die within 5
      years following initial diagnosis. Recently, integrative genomic analyses led to
      the proposal of a molecular classification of GC into four subtypes,
      i.e.,microsatellite-instable, Epstein-Barr virus-positive, chromosomal-instable
      (CIN), and genomically stable GCs. Molecular classification of GC advances our
      knowledge of the biology of GC and may have implications for diagnostics and
      patient treatment. Diagnosis of microsatellite-instable GC and Epstein-Barr virus
      positive GC is more or less straightforward. Microsatellite instability can be
      tested by immunohistochemistry (MLH1, PMS2, MSH2, and MSH6) and/or molecular
      biological analysis. Epstein-Barr virus-positive GC can be tested by in situ
      hybridization (Epstein-Barr virus encoded small RNA). However, with regard to
      CIN, testing may be more complicated and may require a more in-depth knowledge of
      the underlying mechanism leading to CIN. In addition, CIN GC may not constitute a
      distinct subgroup but may rather be a compilation of a more heterogeneous group
      of tumors. In this review, we aim to clarify the definition of CIN and to point
      out the molecular mechanisms leading to this molecular phenotype and the
      challenges faced in characterizing this type of cancer.

PMID- 28431275
TI  - Learning Non-rigid Deformations for Robust, Constrained Point-based Registration
      in Image-Guided MR-TRUS Prostate Intervention.
AB  - Accurate and robust non-rigid registration of pre-procedure magnetic resonance
      (MR) imaging to intra-procedure trans-rectal ultrasound (TRUS) is critical for
      image-guided biopsies of prostate cancer. Prostate cancer is one of the most
      prevalent forms of cancer and the second leading cause of cancer-related death in
      men in the United States. TRUS-guided biopsy is the current clinical standard for
      prostate cancer diagnosis and assessment. State-of-the-art, clinical MR-TRUS
      image fusion relies upon semi-automated segmentations of the prostate in both the
      MR and the TRUS images to perform non-rigid surface-based registration of the
      gland. Segmentation of the prostate in TRUS imaging is itself a challenging task
      and prone to high variability. These segmentation errors can lead to poor
      registration and subsequently poor localization of biopsy targets, which may
      result in false-negative cancer detection. In this paper, we present a non-rigid
      surface registration approach to MR-TRUS fusion based on a statistical
      deformation model (SDM) of intra-procedural deformations derived from clinical
      training data. Synthetic validation experiments quantifying registration volume
      of interest overlaps of the PI-RADS parcellation standard and tests using
      clinical landmark data demonstrate that our use of an SDM for registration, with
      median target registration error of 2.98 mm, is significantly more accurate than
      the current clinical method. Furthermore, we show that the low-dimensional SDM
      registration results are robust to segmentation errors that are not uncommon in
      clinical TRUS data.

PMID- 28431276
TI  - Enzymatic activity, gene expression and posttranslational modifications of
      photosynthetic and non-photosynthetic phosphoenolpyruvate carboxylase in ammonium
      stressed sorghum plants.
AB  - Sorghum plants grown with 5mM (NH4)2SO4 showed symptoms of stress, such as
      reduced growth and photosynthesis, leaf chlorosis, and reddish roots.
      Phosphoenolpyruvate carboxylase (PEPC) activity, by supplying carbon skeletons
      for ammonium assimilation, plays a pivotal role in tolerance to ammonium stress.
      This work investigated the effect of ammonium nutrition on PPC and PPCK gene
      expression, on PEPC activity, and on post-translational modifications (PTMs) of
      PEPC in leaves and roots of sorghum plants. Ammonium increased PEPC kinase
      (PEPCk) activity and the phosphorylation state of PEPC in leaves, both in light
      and in the dark, due to increased PPCK1 expression in leaves. This result
      resembled the effect of salinity on sorghum leaf PEPC and PEPCk, which is thought
      to allow a better functioning of PEPC in conditions that limit the income of
      reduced C. In roots, ammonium increased PEPC activity and the amount of
      monoubiquitinated PEPC. The first effect was related to increased PPC3 expression
      in roots. These results highlight the relevance of this specific isoenzyme (PPC3)
      in sorghum responses to ammonium stress. Although the role of monoubiquitination
      is not fully understood, it also increased in germinating seeds along with
      massive mobilization of reserves, a process in which the anaplerotic function of
      PEPC is of major importance.

PMID- 28431277
TI  - Endocrine disruption by environmental gestagens in amphibians - A short review
      supported by new in vitro data using gonads of Xenopus laevis.
AB  - Endocrine disruption caused by various anthropogenic compounds is of persisting
      concern, especially for aquatic wildlife, because surface waters are the main
      sink of these so-called endocrine disruptors (ED). In the past, research focused
      on (anti)estrogenic, (anti)androgenic, and (anti)thyroidal substances, affecting
      primarily reproduction and development in vertebrates; however, other endocrine
      systems might be also targeted by ED. Environmental gestagens, including natural
      progestogens (e.g. progesterone (P4)) and synthetic progestins used for
      contraception, are supposed to affect vertebrate reproduction via progesterone
      receptors. In the present paper, we review the current knowledge about gestagenic
      effects in amphibians, focussing on reproduction and the thyroid system. In
      addition, we support the literature data with results of recent in vitro
      experiments, demonstrating direct impacts of the gestagens levonorgestrel (LNG)
      and P4 on sexually differentiated gonads of larval Xenopus laevis. The results
      showed a higher susceptibility of female over male gonads to gestagenic ED. Only
      in female gonads LNG, but not P4, had direct inhibitory effects on gene
      expression of steroidogenic acute regulatory protein and P450 side chain cleavage
      enzyme, whereas aromatase expression decreased in reaction to both gestagens.
      Surprisingly, beyond the expected ED effects of gestagens on reproductive
      physiology in amphibians, LNG drastically disrupted the thyroid system, which
      resembles direct effects on thyroid glands and pituitary along the pituitary
      thyroid axis disturbing metamorphic development. In amphibians, environmental
      gestagens not only affect the reproductive system but at least LNG can impact
      also development by disruption of the thyroid system.

PMID- 28431278
TI  - Intranasal oxytocin does not modulate jumping to conclusions in schizophrenia:
      Potential interactions with caudate volume and baseline social functioning.
AB  - BACKGROUND: Patients with schizophrenia (SCZ) tend to sample less information
      when making a decision, jumping to conclusions (JTC) without sufficient evidence.
      This "JTC bias" may be a trait marker of the disease and may not improve with
      antipsychotic treatment. We conducted a double-blind, placebo-controlled trial to
      test whether intranasal oxytocin could reduce JTC in stable, medicated patients
      with SCZ and healthy controls (HCs). We also explored whether striatal volume,
      clinical symptoms, and baseline social functioning (SF) was related to JTC
      performance. METHODS: Forty-three male, medicated SCZ patients (Mean Age: 40.81+/
      11.44) and sixteen HCs (Mean Age: 30.38+/-9.85) participated in a double-blind,
      placebo-controlled, cross-over study. Participants completed the Beads Task on
      two separate visits (minimum 20days apart). Participants were randomized to
      receive either intranasal oxytocin (50IU in solution) or intranasal placebo
      (saline). Twenty of the SCZ patients and all sixteen HCs also provided T1 MRIs (3
      T). RESULTS: Patients with SCZ took fewer draws to decision (DTD) than HCs
      (t(57)=2.78, p=0.007). Oxytocin did not significantly change DTD in patients
      (t(42)=-1.11, p=0.27), nor in HCs (t(15)=-0.62, p=0.55). Exploratory analyses
      found ventral caudate volumes were negatively correlated with DTD (r(18)=-0.50,
      p=0.03) in patients. Moreover, oxytocin was more likely to improve JTC in
      patients with lower baseline SF. However, these exploratory findings did not
      survive correction for multiple comparisons. CONCLUSIONS: We replicate increased
      JTC in SCZ. However, acute intranasal oxytocin did not modify JTC. Future studies
      with larger samples should explore how brain morphology and SF are related to JTC
      performance in patients with SCZ.

PMID- 28431279
TI  - Cognitive control in action: Tracking the dynamics of rule switching in 5- to 8
      year-olds and adults.
AB  - Recent studies have suggested that dissociable processes featuring distinct types
      of inhibition support cognitive control in tasks requiring participants to
      override a prepotent response with a control-demanding alternative response. An
      open question concerns how these processes support cognitive flexibility in rule
      switching tasks. We used a technique known as reach tracking to investigate how 5
      to 8-year-olds (Experiment 1) and adults (Experiment 2) select, maintain, and
      switch between incompatible rule sets in a computerized version of the
      Dimensional Change Card Sort (DCCS). Our results indicate that rule switching
      differentially impacts two key processes underlying cognitive control in children
      and adults. Adult performance also revealed a strong response bias not observed
      in children, which complicated a direct comparison of switching between the age
      groups and reopens questions concerning the relation between child and adult
      performance on the task. We discuss these findings in the context of a
      contemporary model of cognitive control.

PMID- 28431280
TI  - Interleukin-1 receptor associated kinase 1 is a potential therapeutic target of
      anti-inflammatory therapy for systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease
      and currently has no effective therapy. The genome-wide analyses indicate that
      interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the
      susceptibility of SLE in humans. In the present study, we identified that IRAK1
      was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL
      Faslpr/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE
      patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1
      (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses
      and renal injury in B6.lpr mice. IRAK-Inh treatment or knockdown of IRAK1 by
      specific siRNA decreased the relative levels of NF-kappaBp65 phosphorylation in
      human PBMCs from SLE patients. Therefore, IRAK1 may be a potential target for
      anti-inflammatory therapy for SLE and other inflammatory diseases.

PMID- 28431281
TI  - Dengue virus replicates and accumulates in Aedes aegypti salivary glands.
AB  - Dengue virus (DENV) is an RNA virus transmitted among humans by mosquito vectors,
      mainly Aedes aegypti. DENV transmission requires viral dissemination from the
      mosquito midgut to the salivary glands. During this process the virus undergoes
      several population bottlenecks, which are stochastic reductions in population
      size that restrict intra-host viral genetic diversity and limit the efficiency of
      natural selection. Despite the implications for virus transmission and evolution,
      DENV replication in salivary glands has not been directly demonstrated. Here, we
      used a strand-specific quantitative RT-PCR assay to demonstrate that negative
      strand DENV RNA is produced in Ae. aegypti salivary glands, providing conclusive
      evidence that viral replication occurs in this tissue. Furthermore, we showed
      that the concentration of DENV genomic RNA in salivary glands increases
      significantly over time, indicating that active replication likely replenishes
      DENV genetic diversity prior to transmission. These findings improve our
      understanding of the biological determinants of DENV fitness and evolution.

PMID- 28431282
TI  - The role of pharmacologic modulation of autophagy on anal cancer development in
      an HPV mouse model of carcinogenesis.
AB  - Autophagy is an intracellular, catabolic process that maintains cellular health.
      We examined the response of pharmacologic modulation of autophagy in an HPV mouse
      model of anal carcinogenesis. K14E6/E7 mice were treated with the topical
      carcinogen DMBA weekly and assessed for tumors over 20 weeks. Concurrently, they
      were given either chloroquine or BEZ235, to inhibit or induce autophagy,
      respectively. Time to tumor onset was examined. Immunofluorescence (IF) was
      performed for LC3beta and p62 to examine autophagy. All DMBA treated K14E6/E7
      mice developed anal cancer, contrary to zero of the no DMBA treated mice.
      Chloroquine plus DMBA resulted in a significant decrease in the time to tumor
      onset compared to K14E6/E7 treated with DMBA. Only 40% BEZ235 plus DMBA treated
      mice developed anal cancer. Autophagic induction with DMBA and BEZ235, and
      autophagic inhibition with chloroquine were confirmed via IF. Anal carcinogenesis
      can be inhibited or induced via pharmacologic modulation of autophagy.

PMID- 28431283
TI  - Zika virus infection of adult and fetal STAT2 knock-out hamsters.
AB  - Zika virus (ZIKV) infection was investigated in adult and fetal STAT2 knock-out
      (KO) hamsters. Subcutaneous injection of ZIKV of adults resulted in morbidity,
      mortality, and infection of the uterus, placenta, brain, spinal cord, and
      testicles, thus providing an opportunity to evaluate congenital ZIKV infection in
      a second rodent species besides mice. ZIKV-infected cells with morphologies of
      Sertoli cells and spermatogonia were observed in the testes, which may have
      implications for sexual transmission and male sterility. Neonates exposed as
      fetuses to ZIKV at 8 days post-coitus were not smaller than controls.
      Nevertheless, infectious virus and ZIKV RNA was detected in some, but not all,
      placentas and fetal brains of KO hamsters. STAT2 KO hamsters may be useful for
      addressing sexual transmission, pathogenesis, routes of fetal infection, and
      neurological disease outcomes, and may also be used in antiviral or vaccine
      studies to identify intervention strategies.

PMID- 28431284
TI  - Mitovirus UGA(Trp) codon usage parallels that of host mitochondria.
AB  - Mitoviruses replicate in mitochondria of their host fungi. They have small RNA
      genomes that encompass a single ORF encoding the viral RdRp. Since UGA codons
      encode Trp in fungal mitochondria, the RdRp ORF of a typical mitovirus includes
      multiple UGA codons. In some mitoviruses, however, the ORF has no such codons,
      suggesting that these particular viruses may be under selective pressure to
      exclude them. In this report, new evidence is presented that host fungi whose
      mitoviruses have no or few UGA codons are distinctive in also having no or few
      UGA codons in their core mitochondrial genes. Thus, the relative exclusion of
      such codons in a subset of mitoviruses appears to reflect most fundamentally that
      UGA(Trp) is a rare mitochondrial codon in their particular hosts. The fact that
      UGA(Trp) is a rare mitochondrial codon in many fungi appears not to have been
      widely discussed to date.

PMID- 28431285
TI  - Two benzoyl coumarin amide fluorescence chemosensors for cyanide anions.
AB  - Two new benzoyl coumarin amide derivatives with ortho hydroxyl benzoyl as
      terminal group have been synthesized. Their photophysical properties and
      recognition properties for cyanide anions in acetonitrile have also been
      examined. The influence of electron donating diethylamino group in coumarin ring
      and hydroxyl in benzoyl group on recognition properties was explored. The results
      indicate that the compounds can recognize cyanide anions with obvious absorption
      and fluorescence spectral change and high sensitivity. The import of diethylamine
      group increases smartly the absorption ability and fluorescence intensity of the
      compound, which allows the recognition for cyanide anions can be observed by
      naked eyes. The in situ hydrogen nuclear magnetic resonance spectra combining
      photophysical properties change and job's plot data confirm that Michael addition
      between the chemosensors and cyanide anions occurs. Molecular conjugation is
      interrupted, which leads to fluorescence quenching. At the same time, there is a
      certain extent hydrogen bond reaction between cyanide and hydroxyl group in the
      compounds, which is beneficial to the recognition.

PMID- 28431286
TI  - Age-related changes in corticospinal excitability and intracortical inhibition
      after upper extremity motor learning: a systematic review and meta-analysis.
AB  - It is unclear how old age affects the neuronal mechanisms of motor learning. We
      reviewed the neuronal mechanisms of how healthy old and young adults acquire
      motor skills as assessed with transcranial magnetic stimulation. Quantitative
      meta-analyses of 11 studies, involving ballistic and visuomotor tasks performed
      by upper extremity muscles in 132 healthy old and 128 young adults, revealed that
      the motor practice-induced increase in corticospinal excitability (CSE) is task
      dependent but not age-dependent, with an increase in CSE in both age groups after
      visuomotor but not ballistic training. In addition, short-interval intracortical
      inhibition (SICI) is reduced in old but not young adults, but only after
      visuomotor practice. In addition, correlation analyses in 123 old and 128 young
      adults showed that the magnitude of motor skill acquisition did not correlate
      with increases in CSE or decreases in SICI in either age group. Thus, there are
      subtle age-related differences in use-dependent plasticity but increases in CSE
      or decreases in SICI are not related to motor skill acquisition in healthy young
      or old adults.

PMID- 28431287
TI  - Age and gender effects of 11C-ITMM binding to metabotropic glutamate receptor
      type 1 in healthy human participants.
AB  - We examined possible age- and gender-related changes in binding of the selective
      antagonist N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C
      methoxy-N-methylbenzamide (11C-ITMM) to metabotropic glutamate receptor type 1 in
      healthy human brains. Dynamic 11C-ITMM positron emission tomography scans (90
      min) with serial arterial blood sampling were performed in 15 young and 24 older
      healthy adult volunteers. The total distribution volume (VT) of several brain
      regions was estimated with 2-tissue compartment model analysis. The VTs of the
      cerebellar cortex, parietal cortex, putamen, amygdala, and hippocampus in older
      adult participants were significantly higher than in young participants. The age
      related VT increase was only observed in male participants. Our data suggest that
      an age-dependent increase in metabotropic glutamate receptor type 1 availability
      in several brain regions may exist predominantly in males.

PMID- 28431289
TI  - Klotho, APOEepsilon4, cognitive ability, brain size, atrophy, and survival: a
      study in the Aberdeen Birth Cohort of 1936.
AB  - A single copy of klotho allele KL-VS is associated with longevity, better health,
      increased cognition, and bigger regional brain volume. However, its longitudinal
      effects on cognition and brain volumes, both global and regional, in late life
      are unclear. In this study we show that, relative to noncarriers, KL-VS
      heterozygotes had (1) shorter survival; (2) smaller white matter volumes; (3)
      slower cognitive decline; and (4) greater right frontal lobe volumes. The KL-VS
      heterozygote survival and white matter volume disadvantages were unexpected. A
      possible explanation for these results in the context of the literature is a
      potential interaction between the environment and/or age of the participants,
      leading to a heterozygote disadvantage. The longitudinal cognitive trajectories
      indicate that heterozygotes would have an advantage in very late life.
      Collectively these results suggest that the genotype-survival advantage of the KL
      VS allele is age-dependent and possibly mediated through differential cognition
      and brain volume.

PMID- 28431290
TI  - Predicting success of vagus nerve stimulation (VNS) from EEG symmetry.
AB  - PURPOSE: Vagus nerve stimulation (VNS) has shown to be an effective treatment for
      drug resistant epilepsy, with achieving more than 50% seizure reduction in one
      third of the treated patients. In order to predict which patients will profit
      from VNS, we previously found that a low pairwise derived Brain Symmetry Index
      (pdBSI) could potentially predict good responders to VNS treatment. These
      findings however have to be validated before they can be generalized. METHODS: 39
      patients (age 18-68 years) with medically intractable epilepsy who were referred
      for an implanted VNS system were included. Routine EEG registrations, recorded
      before implantation, were analyzed. Artefact-free epochs with eyes open and eyes
      closed were quantitatively analyzed. The pdBSI was tested for relation with VNS
      outcome one year after surgery. RESULTS: Twenty-three patients (59%) obtained a
      reduction in seizure frequency, of whom ten (26%) had a reduction of at least 50%
      (good responders) and thirteen (33%) a reduction of less than 50% (moderate
      responders). Sixteen patients without seizure reduction are defined as non
      responders. No significant differences were found in the pdBSI of good responders
      (mean 0.27), moderate responders (mean 0.26) and non-responders (mean 0.25)
      (p>0.05). Besides seizure reduction, many patients (56%) reported additional
      positive effects of VNS in terms of seizure duration, seizure intensity and/or
      postictal recovery. CONCLUSION: EEG features that correlate with VNS therapy
      outcome may enable better patient selection and prevent unnecessary VNS surgery.
      Contrary to earlier findings, this validation study suggests that pdBSI might not
      be helpful to predict VNS therapy outcome.

PMID- 28431288
TI  - Longitudinal whole-brain atrophy and ventricular enlargement in nondemented
      Parkinson's disease.
AB  - We investigated whole-brain atrophy and ventricular enlargement over 18 months in
      nondemented Parkinson's disease (PD) and examined their associations with
      clinical measures and baseline CSF markers. PD subjects (n = 100) were classified
      at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and
      no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change
      (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and
      ventricular enlargement (VIENA) respectively. PD-MCI showed increased global
      atrophy (-1.1% +/- 0.8%) and ventricular enlargement (6.9 % +/- 5.2%) compared
      with both PD-NC (PBVC: -0.4 +/- 0.5, p < 0.01; VIENA: 2.1% +/- 4.3%, p < 0.01)
      and healthy controls. In a subset of 35 PD subjects, CSF levels of tau, and
      Abeta42/Abeta40 ratio were correlated with PBVC and ventricular enlargement
      respectively. The sample size required to demonstrate a 20% reduction in PBVC and
      VIENA was approximately 1/15th of that required to detect equivalent changes in
      cognitive decline. These findings suggest that longitudinal MRI measurements have
      potential to serve as surrogate markers to complement clinical assessments for
      future disease-modifying trials in PD.

PMID- 28431291
TI  - Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to
      hippocampal sclerosis: No influence on seizure outcome after surgery.
AB  - PURPOSE: To assess the clinical significance of temporal pole abnormalities
      (temporopolar blurring, TB, and temporopolar atrophy, TA) detected by using 3
      Tesla MRI in the preoperative workup in patients with temporal lobe epilepsy due
      to hippocampal sclerosis (TLE-HS) who underwent surgery. METHODS: We studied 78
      consecutive patients with TLE-HS who underwent surgery and were followed up for
      at least 2 years. Based on findings of pre-surgical 3 Tesla MRI, patients were
      subdivided in subgroups according to the presence of TB or TA. Subgroups were
      compared on demographic, clinical, neuropsychological data and seizure outcome.
      RESULTS: TB was found in 39 (50%) patients, while TA was found in 32 (41%)
      patients, always ipsilateral to HS, with a considerable degree of overlap (69%)
      between TB and TA (p=0.01). Patients with temporopolar abnormalities did not
      significantly differ from those without TB or TA with regard to sex, age, age of
      epilepsy onset, duration of epilepsy, history of febrile convulsions or birth
      complications, side of surgery, seizure frequency at surgery, presence of GTCSs,
      and, in particular, seizure outcome. On the other hand, TB patients show a less
      frequent family history of epilepsy (p<.05) while age at epilepsy onset showed a
      trend to be lower in the TB group (p=.09). Patients with temporopolar atrophy did
      not significantly differ from those without TA on any variable, except for age at
      epilepsy onset, which was significantly lower for the TA group (p<.05). History
      of birth complications and longer duration of epilepsy also showed a trend to be
      associated with TA (p=.08). Multivariate analysis corroborated the association
      between temporopolar abnormalities and absence of family history of epilepsy and
      history of birth complications. CONCLUSIONS: High-field 3 T MRI in the
      preoperative workup for epilepsy surgery confirms that temporopolar abnormalities
      are frequent findings in TLE-HS patients and may be helpful to lateralize the
      epileptogenic zone. Their presence did not influence seizure outcome.

PMID- 28431292
TI  - Cannabis and cue-induced craving in cocaine-dependent individuals: A pilot study.
AB  - BACKGROUND: Cannabis consumption is common among cocaine users; however, little
      is known about its effect on cocaine craving. The objective of this study was to
      assess whether cannabis co-use is associated with lower cue-induced cocaine
      craving in non-treatment-seeking cocaine-dependent individuals. METHODS: Data
      from twenty-eight cocaine-dependent men were analyzed in this pilot study.
      Cocaine-dependent subjects (n=12) were compared with cocaine-dependent subjects
      who also abused or were dependent on cannabis (n=16). After at least 72h of
      cocaine abstinence, verified using the Timeline Followback and a drug screening
      test, subjects participated in a functional magnetic resonance imaging session
      during which neutral and drug cue video sequences were presented. Each sequence
      comprised four video blocks alternating with resting blocks. We report here
      subjective craving measures that were collected using the Visual Analog Scale,
      administered before and after each video block as per standard craving
      measurement paradigms. RESULTS: Cocaine craving was successfully induced, with no
      significant difference in cue-induced craving between the two groups. However,
      post-hoc analyses revealed a significant increase in pre-video cocaine craving
      scores over time among individuals with cannabis use disorders. CONCLUSION: We
      could not highlight significant differences in cocaine craving induction between
      groups, but we observed a possible deficit in craving decay in the cocaine and
      cannabis group. In light of this finding, methodology of craving assessment in
      non-treatment-seeking users, particularly when different substances are combined,
      should possibly include outcomes linked to craving decay. Studies examining the
      association between cocaine craving decay and other outcome measures, such as
      relapse, are also warranted.

PMID- 28431293
TI  - Cigarette dependence and depressive symptoms as predictors of smoking status at
      five-year follow-up after a workplace smoking cessation program.
AB  - Workplace smoking cessation interventions increase quit rates compared to no
      treatment or minimal interventions. However, most studies report data up to one
      year. This study aims to evaluate long-term effects of a worksite smoking
      cessation intervention based on cognitive behavioral cessation groups combined
      with first-line medications, and determine to what extent cigarette dependence
      (FTCD) and depressive symptoms may influence results at five-year follow-up.
      Participants were invited to answer a short survey five years after starting the
      program. A total of 90.4% (n=227) of those who had attended at least one
      treatment session and were alive, completed the survey. At the five-year follow
      up, 29.5% participants reported continuous abstinence. Low scores in the FTCD and
      low depressive symptoms at baseline predicted continuous abstinence. Three out of
      four continuous abstainers at twelve months remained abstinent at the five-year
      follow-up. The study shows that workplace smoking cessation interventions have
      long-term effects and supports the traditional one-year follow-up period to
      assess smoking cessation.

PMID- 28431294
TI  - Exploring the experience of episodic past, future, and counterfactual thinking in
      younger and older adults: A study of a Colombian sample.
AB  - Although extant evidence suggests that many neural and cognitive mechanisms
      underlying episodic past, future, and counterfactual thinking overlap, recent
      results have uncovered differences among these three processes. However, the
      extent to which there may be age-related differences in the phenomenological
      characteristics associated with episodic past, future and counterfactual thinking
      remains unclear. This study used adapted versions of the Memory Characteristics
      Questionnaire and the Autobiographical Interview in younger and older adults to
      investigate the subjective experience of episodic past, future and counterfactual
      thinking. The results suggest that, across all conditions, younger adults
      generated more internal details than older adults. However, older adults
      generated more external details for episodic future and counterfactual thinking
      than younger adults. Additionally, younger and older adults generated more
      internal details, and gave higher sensory and contextual ratings, for memories
      rather than future and counterfactual thoughts. Methodological and theoretical
      consequences for extant theories of mental simulation are discussed.

PMID- 28431295
TI  - Clove and rosemary essential oils and encapsuled active principles (eugenol,
      thymol and vanillin blend) on meat quality of feedlot-finished heifers.
AB  - Forty Nellore heifers were fed (73days) with different diets: with or without
      essential oils (clove and/or rosemary essential oil) and/or active principle
      blend (eugenol, thymol and vanillin). The pH, fat thickness, marbling, muscle
      area and water losses (thawing and drip) were evaluated 24h post mortem on the
      Longissimus thoracis, and the effects of aging (14days) was evaluated on the meat
      cooking losses, color, texture and lipid oxidation. Antioxidant activity was also
      evaluated. Treatments had no effect (P>0.05) on pH, fat thickness, marbling,
      muscle area, thawing and drip losses. However, treatments affected (P<0.05)
      cooking losses, color, texture and lipid oxidation. The diets with essential oil
      and the active principle blend reduced the lipid oxidation and reduced the color
      losses in relation to control diet. Aging affected (P<0.05) texture and lipid
      oxidation. The essential oil and active principles or its blend have potential
      use in animal feed aiming to maintain/improve meat quality during shelf-life.

PMID- 28431296
TI  - Survival and transfer efficacy of mixed strain Salmonella enterica ser.
      Typhimurium from beef burgers to abiotic surfaces and determination of individual
      strain contribution.
AB  - The aim of the study was to evaluate the survival and transfer efficacy of 3
      Salmonella Typhimurium strains from beef burgers to abiotic surfaces and
      determine the individual strain distribution. S. Typhimurium population on beef
      burgers during incubation remained constant at initial levels of contamination
      approximately 3 and 5 log CFU/g. Additionally, the survival of pathogens on
      soiled HDPE surfaces was significant during incubation at both initial inocula,
      while ca 1.5 log CFU/cm2 reduction was observed at 168h. The log transformed
      transfer rate (log10Tr) was -1.86+/-0.23 and -1.75+/-0.40 for high and low
      inoculum. The level of initial contamination did not have any statistical
      important impact on bacterial transfer (P>0.05). In addition, the results
      regarding the strain contribution revealed rather random individual proportion of
      each strain, recovered from HDPE, SS surfaces and beef burgers. However, the
      dominance of each strain was strongly dependent on surface at low inoculum and
      time in case of high inoculum. This observed strain variability during survival
      and transfer of S. Typhimurium might be of great importance in order to
      understand and consequently limit the possibility of cross contamination during
      food processing in a common household.

PMID- 28431298
TI  - Bioluminescence emissions of female fireflies of the species Luciola praeusta.
AB  - Numerous investigations have been carried out on bioluminescence emissions from
      male fireflies. However, very few observations have been made on the emitted
      light from female specimens. Even in those, apart from observing responses from
      females to courtship flashes from conspecific males, detailed studies have not
      been performed. Here we present a first report on the light of female fireflies
      of the Indian species Luciola praeusta Kiesenwetter 1874
      (Coleoptera:Lampyridae:Luciolinae). In the steady-state emission spectrum over
      the temperature range of 20-40 degrees C, the peak wavelength is the same as,
      while the full width at half maximum is larger than, that of a male specimen of
      this species. Increase in temperature up to 45 degrees C brings out a change in
      both the peak and FWHM values, shifting towards red. In the time-resolved
      measurement, duration of a flash, which is noticeably larger than that of a male,
      is found to decrease exponentially with temperature at 20-40 degrees C. Further
      increase in the temperature produces a minimum flash duration at 41.5 degrees C,
      and beyond this causes a considerable increase in duration for small increase in
      temperature. Additionally, lowering the temperature below 20 degrees C makes a
      single flash appear as a combination of two or three flashes.

PMID- 28431297
TI  - Nano-zirconia - Evaluation of its antioxidant and anticancer activity.
AB  - Bioactivity of nanomaterials largely depends on its size, shape and crystalline
      nature. In this work, the smaller sized spherical shaped nano-zirconia (ZrO2 NPs)
      (of ~9 to 11nm) was fabricated and studied its biological activity especially
      antioxidant and cytotoxicity against human colon carcinoma (HCT-116) and human
      lung carcinoma (A-549) cell lines. To have its real applications in biological
      aspects readily available Eucalyptus globulus (E. globulus) leaf extract was used
      as an effective capping and reducing agent for its synthesis. The prepared ZrO2
      NPs was characterized by using different sophisticated instrumentations such as
      UV-visible spectrophotometer, XRD, FTIR, TEM, SAED, EDX, DLS and fluorescence
      spectroscopy. Cellular mitochondrial activity i.e. cell viability was measured by
      MTT assay and anti-oxidant activity was determined by DPPH assay. The smaller
      sized ZrO2 NPs showed strong antioxidant activity as well as cytotoxicity on
      human cancer cell lines. Comparative cytotoxic studies were conducted on human
      cancerous cell lines using different techniques. Results confirmed the efficient
      anti-cancer activities of the fabricated ZrO2 NPs towards the tested cell lines
      as well as efficient anti-oxidant activity. This is the first study in which E.
      globulus leaf extract was used to synthesize smaller spherical shaped ZrO2 NPs
      for improved bioactivity i.e. antioxidant and cytotoxicity.

PMID- 28431299
TI  - Not that neglected! Base rates influence related and unrelated judgments.
AB  - It is claimed that people are unable (or unwilling) to incorporate prior
      probabilities into posterior assessments, such as their estimation of the
      likelihood of a person with characteristics typical of an engineer actually being
      an engineer given that they are drawn from a sample including a very small number
      of engineers. This paper shows that base rates are incorporated in
      classifications (Experiment 1) and, moreover, that base rates also affect
      unrelated judgments, such as how well a provided description of a person fits a
      stereotypical engineer (Experiment 2). Finally, Experiment 3 shows that
      individuals who make both types of assessments - though using base rates to the
      same extent in the former judgments - are able to decrease the extent to which
      they incorporate base rates in the latter judgments.

PMID- 28431300
TI  - Post-error response inhibition in high math-anxious individuals: Evidence from a
      multi-digit addition task.
AB  - The aim of the study was to investigate how high math-anxious (HMA) individuals
      react to errors in an arithmetic task. Twenty HMA and 19 low math-anxious (LMA)
      individuals were presented with a multi-digit addition verification task and were
      given response feedback. Post-error adjustment measures (response time and
      accuracy) were analyzed in order to study differences between groups when faced
      with errors in an arithmetical task. Results showed that both HMA and LMA
      individuals were slower to respond following an error than following a correct
      answer. However, post-error accuracy effects emerged only for the HMA group,
      showing that they were also less accurate after having committed an error than
      after giving the right answer. Importantly, these differences were observed only
      when individuals needed to repeat the same response given in the previous trial.
      These results suggest that, for HMA individuals, errors caused reactive
      inhibition of the erroneous response, facilitating performance if the next
      problem required the alternative response but hampering it if the response was
      the same. This stronger reaction to errors could be a factor contributing to the
      difficulties that HMA individuals experience in learning math and doing math
      tasks.

PMID- 28431301
TI  - Diversity training for the community aged care workers: A conceptual framework
      for evaluation.
AB  - Older Australians are an increasingly diverse population, with variable
      characteristics such as culture, sexual orientation, socioeconomic status, and
      physical capabilities potentially influencing their participation in healthcare.
      In response, community aged care workers may need to increase skills and uptake
      of knowledge into practice regarding diversity through appropriate training
      interventions. Diversity training (DT) programs have traditionally existed in the
      realm of business, with little research attention devoted to scientifically
      evaluating the outcomes of training directed at community aged care workers. A DT
      workshop has been developed for community aged care workers, and this paper
      focuses on the construction of a formative evaluative framework for the workshop.
      Key evaluation concepts and measures relating to DT have been identified in the
      literature and integrated into the framework, focusing on five categories:
      Training needs analysis; Reactions; Learning outcomes, Behavioural outcomes and
      Results The use of a mixed methods approach in the framework provides an
      additional strength, by evaluating long-term behavioural change and improvements
      in service delivery. As little is known about the effectiveness of DT programs
      for community aged care workers, the proposed framework will provide an empirical
      and consistent method of evaluation, to assess their impact on enhancing older
      people's experience of healthcare.

PMID- 28431302
TI  - Quality of life in survivors of oropharyngeal cancer: A systematic review and
      meta-analysis of 1366 patients.
AB  - Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is rapidly
      increasing in incidence and has a favourable prognosis compared with HPV-negative
      disease. Current combined therapies include significant risks of morbidity for
      the growing group of survivors. This systematic review and meta-analysis
      investigates how treatment affects quality of life (QoL) in survivors of
      oropharyngeal cancer. PubMed, EMBASE and the Cochrane Library were systematically
      searched for all studies reporting patient-assessed QoL at least 1 year after
      treatment for OPC. In a meta-analysis, weighted average QoL scores from the four
      most commonly utilised QoL instruments were compared with baseline and reference
      group scores using the concept of minimal clinically important difference. The
      meta-analysis included data from 1366 patients from 25 studies and 12 countries.
      The European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core-30 (EORTC QLQ-C30) was answered by 704 patients, 644 patients
      answered the EORTC QLQ Head and Neck-35 (H&N-35), 474 patients answered the
      University of Washington Quality of Life Questionnaire, and 381 patients answered
      the M. D. Anderson Dysphagia Inventory. Moderate to large clinically important
      deteriorations in QoL were found in the domains dry mouth and sticky saliva for
      the EORTC QLQ-H&N35, saliva, chewing, swallowing, speech, taste, appearance and
      shoulder for the University of Washington Quality of Life Questionnaire, and the
      global, physical and emotional subscales for the M. D. Anderson Dysphagia
      Inventory. In conclusion, survivors of OPC face clinically important
      deteriorations in QoL that most markedly centre on xerostomia, dysphagia and
      chewing. These ailments indicate a potential for improvement in patient
      management.

PMID- 28431303
TI  - Circular shape constrained fuzzy clustering (CiscFC) for nucleus segmentation in
      Pap smear images.
AB  - Accurate detection and segmentation of cell nucleus is the precursor step towards
      computer aided analysis of Pap smear images. This is a challenging and complex
      task due to degree of overlap, inconsistent staining and poor contrast. In this
      paper, a novel nucleus segmentation method is proposed by incorporating a
      circular shape function in fuzzy clustering. The proposed method was evaluated
      quantitatively and qualitatively using the Overlapping Cervical Cytology Image
      Segmentation Challenge - ISBI 2014 challenge dataset comprised of 945 overlapping
      Pap smear images. It achieved superior performance in terms of Dice similarity
      coefficient of 0.938, pixel-based recall 0.939 and object based precision 0.968.
      The results were compared with the standard fuzzy c-means (FCM) clustering, ISBI
      2014 challenge submissions and recent state-of-the-art methods. The outcome shows
      that the new approach can produce more accurate nucleus boundaries while keeping
      high level of precision and recall.

PMID- 28431304
TI  - "Diabetic striatopathy" and ketoacidosis: Report of two cases and review of
      literature.
AB  - "Diabetic striatopathy" is characterized by dyskinesias with basal ganglia
      hyperintensities on neuroimaging. It is usually reported in elderly females with
      hyperglycemic hyperosmolar state and rare in patients with diabetic ketoacidosis.
      Here, we report two young males with diabetic ketoacidosis presenting as
      striatopathy, along with review of literature.

PMID- 28431305
TI  - Cognitive-behavioral high parental involvement treatments for pediatric obsessive
      compulsive disorder: A meta-analysis.
AB  - A meta-analysis on the efficacy of cognitive-behavior-family treatment (CBFT) on
      children and adolescents with obsessive-compulsive disorder (OCD) was
      accomplished. The purposes of the study were: (a) to estimate the effect
      magnitude of CBFT in ameliorating obsessive-compulsive symptoms and reducing
      family accommodation on pediatric OCD and (b) to identify potential moderator
      variables of the effect sizes. A literature search enabled us to identify 27
      studies that fulfilled our selection criteria. The effect size index was the
      standardized pretest-postest mean change index. For obsessive-compulsive
      symptoms, the adjusted mean effect size for CBFT was clinically relevant and
      statistically significant in the posttest (dadj=1.464). For family accommodation
      the adjusted mean effect size was also positive and statistically significant,
      but in a lesser extent than for obsessive-compulsive symptoms (dadj=0.511).
      Publication bias was discarded as a threat against the validity of the meta
      analytic results. Large heterogeneity among effect sizes was found. Better
      results were found when CBFT was individually applied than in group (d+=2.429 and
      1.409, respectively). CBFT is effective to reduce obsessive-compulsive symptoms,
      but offers a limited effect for family accommodation. Additional modules must be
      included in CBFT to improve its effectiveness on family accommodation.

PMID- 28431306
TI  - Difference optimization: Automatic correction of relative frequency and phase for
      mean non-edited and edited GABA 1H MEGA-PRESS spectra.
AB  - Phase and frequency corrections of magnetic resonance spectroscopic data are of
      major importance to obtain reliable and unambiguous metabolite estimates as
      validated in recent research for single-shot scans with the same spectral
      fingerprint. However, when using the J-difference editing technique 1H MEGA
      PRESS, misalignment between mean edited (ON?) and non-edited (OFF?) spectra that
      may remain even after correction of the corresponding individual single-shot
      scans results in subtraction artefacts compromising reliable GABA quantitation.
      We present a fully automatic routine that iteratively optimizes simultaneously
      relative frequencies and phases between the mean ON? and OFF?1H MEGA-PRESS
      spectra while minimizing the sum of the magnitude of the difference spectrum (L1
      norm). The proposed method was applied to simulated spectra at different SNR
      levels with deliberately preset frequency and phase errors. Difference
      optimization proved to be more sensitive to small signal fluctuations, as e.g.
      arising from subtraction artefacts, and outperformed the alternative spectral
      registration approach, that, in contrast to our proposed linear approach, uses a
      nonlinear least squares minimization (L2 norm), at all investigated levels of
      SNR. Moreover, the proposed method was applied to 47 MEGA-PRESS datasets acquired
      in vivo at 3T. The results of the alignment between the mean OFF? and ON? spectra
      were compared by applying (a) no correction, (b) difference optimization or (c)
      spectral registration. Since the true frequency and phase errors are not known
      for in vivo data, manually corrected spectra were used as the gold standard
      reference (d). Automatically corrected data applying both, method (b) or method
      (c), showed distinct improvements of spectra quality as revealed by the mean
      Pearson correlation coefficient between corresponding real part mean DIFF?
      spectra of Rbd=0.997+/-0.003 (method (b) vs. (d)), compared to Rad=0.764+/-0.220
      (method (a) vs. (d)) with no alignment between OFF? and ON?. Method (c) revealed
      a slightly lower correlation coefficient of Rcd=0.972+/-0.028 compared to Rbd,
      that can be ascribed to small remaining subtraction artefacts in the final DIFF?
      spectrum. In conclusion, difference optimization performs robustly with no
      restrictions regarding the input data range or user intervention and represents a
      complementary tool to optimize the final DIFF? spectrum following the mandatory
      frequency and phase corrections of single ON and OFF scans prior to averaging.

PMID- 28431307
TI  - Identifying longitudinal sustainable hierarchies in activities of daily living.
AB  - Activities of daily living serve as an indicator of progression in disability and
      rehabilitation. It is know that some of the measurement scales used show
      hierarchical properties indicating that activities of daily living are lost and
      gained in a consistent pattern. Few studies have investigated the extent to which
      these patterns are sustained across time and across a range of disability. The
      study aimed to investigate the hierarchical properties of the activity of daily
      living items in the ValGraf functional ability scale, to establish if there is a
      hierarchy of items in the scale and to study the sustainability of the hierarchy
      over time. Secondary analysis of a retrospective database from 13,113 people over
      65 years in 105 nursing homes in northern Italy, between 2008 and 2013 was
      conducted. Data were gathered 6-monthly and analysed using Mokken scaling to
      identify a hierarchy of items in the scale and if this was sustainable over time.
      A sustainable hierarchy of items was observed running in difficulty from urinary
      incontinence to feeding. The hierarchical structure of the activities of daily
      living observed in the present study is stable over time meaning that changes in
      total score for these items can be compared meaningfully across time.

PMID- 28431308
TI  - Hyperexcitability of inferior colliculus and acoustic startle reflex with age
      related hearing loss.
AB  - Chronic tinnitus and hyperacusis often develop with age-related hearing loss
      presumably due to aberrant neural activity in the central auditory system (CAS)
      induced by cochlear pathologies. However, the full spectrum of physiological
      changes that occur in the CAS as a result age-related hearing loss are still
      poorly understood. To address this issue, neurophysiological measures were
      obtained from the cochlea and the inferior colliculus (IC) of 2, 6 and 12 month
      old C57BL/6J mice, a mouse model for early age-related hearing loss. Thresholds
      of the compound action potentials (CAP) in 6 and 12 month old mice were
      significantly higher than in 2 month old mice. The sound driven and spontaneous
      firing rates of IC neurons, recorded with 16 channel electrodes, revealed mean IC
      thresholds of 22.8 +/- 6.5 dB (n = 167) at 2 months, 37.9 +/- 6.2 dB (n = 132) at
      6 months and 47.1 +/- 15.3 dB (n = 151) at 12 months of age consistent with the
      rise in CAP thresholds. The characteristic frequencies (CF) of IC neurons ranged
      from 3 to 32 kHz in 2 month old mice; the upper CF ranged decreased to 26 kHz and
      16 kHz in 6 and 12 month old mice respectively. The percentage of IC neurons with
      CFs between 8 and 12 kHz increased from 36.5% in 2 month old mice, to 48.8% and
      76.2% in 6 and 12 month old mice, respectively, suggesting a downshift of IC CFs
      due to the high-frequency hearing loss. The average spontaneous firing rate
      (SFRs) of all recorded neurons in 2 month old mice was 3.2 +/- 2.5 Hz (n = 167).
      For 6 and 12 month old mice, the SFRs of low CF neurons (<8 kHz) was maintained
      at 3-6 spikes/s; whereas SFRs of IC neurons with CFs > 8 kHz increased to 13.0 +/
      15.4 (n = 68) Hz at 6 months of age and then declined to 4.8 +/- 7.4 (n = 110)
      spikes/s at 12 months of age. In addition, sound-evoked activity at
      suprathreshold levels at 6 months of age was much higher than at 2 and 12 months
      of age. To evaluate the behavioral consequences of sound evoked hyperactivity in
      the IC, the amplitude of the acoustic startle reflex was measured at 4, 8 and 16
      kHz using narrow band noise bursts. Acoustic startle reflex amplitudes in 6 and
      12 month old mice (n = 4) were significantly larger than 2 month old mice (n = 4)
      at 4 and 8 kHz, but not 16 kHz. The enhanced reflex amplitudes suggest that high
      intensity, low-frequency sounds are perceived as louder than normal in 6 and 12
      month old mice compared to 2 month olds. The increased spontaneous activity,
      particularly at 6 months, may be related to tinnitus whereas the increase in
      sound-evoked activity and startle reflex amplitudes may be related to
      hyperacusis.

PMID- 28431309
TI  - Brief critical examination of the article: "Impulse noise injury prediction based
      on the cochlear energy" by Zagadou, Chan, Ho and Shelly.

PMID- 28431310
TI  - Characterization of bacterial communities of donkey milk by high-throughput
      sequencing.
AB  - The interest in donkey milk (DM) is growing because of its functional properties
      and nutritional value, especially for children with allergies and food
      intolerances. However, most of the available reports of DM microbiota are based
      on culture-dependent methods to investigate food safety issues and the presence
      of lactic acid bacteria (LAB). The aim of this study was to determine the
      composition of DM bacterial communities using a high-throughput sequencing (HTS)
      approach. Bulk milk samples from Italian donkey dairy farms from two consecutive
      years were analysed using the MiSeq Illumina platform. All sample reads were
      classified into five phyla: Proteobacteria, Firmicutes, Bacteroidetes,
      Actinobacteria, and Verrucomicrobia. The most prevalent genera-Pseudomonas,
      Ralstonia, Acinetobacter, Cupriavidus, Citrobacter and Sphingobacterium-were Gram
      negative bacteria. The core microbiota was composed of genera that comprise
      commonly associated milk bacteria, LAB and species normally found in soil, water
      and plants. Reads assigned to LAB genera-Streptococcus, Lactococcus,
      Enterococcus, Leuconostoc, Lactobacillus, and Carnobacterium-corresponded on
      average to 2.55% of the total reads per sample. Among these, the distribution of
      reads assigned to coccus- and bacillus-shaped LAB was variable between and within
      the farms, confirming their presence and suggesting a complex population of these
      bacteria in DM. The present study represents a general snapshot of the DM
      microbial population, underlining its variability and motivating further studies
      for the exploitation of the technological potential of bacteria naturally present
      in DM.

PMID- 28431311
TI  - The low-lying electronic states and optical schemes for the laser cooling of the
      BH+ and BH- ions.
AB  - The potential energy curves and transition dipole moments for the 12Sigma+,
      22Sigma+, 12Pi and 22Pi electronic states of the two molecules are calculated
      using multi-reference configuration interaction and the large basis sets aug-cc
      pwCV5Z. Based on the obtained potential energy curves, the rotational and
      vibrational energy levels of the states are obtained by solving the Schrodinger
      equation of nuclear motion, and the spectroscopic parameters are then obtained by
      fitting the energy levels to Dunham series expansions. The spin-orbit coupling
      effect of the 2Pi states for both the BH+ cation and BH- anion are calculated.
      Highly diagonally distributed Franck-Condon factors are determined for the
      12Sigma+ (v"=0)<->12Pi (v'=0) transition, f00 (BH+)=0.943, while the Franck
      Condon factors for the 12Pi (v"=0)<->12Sigma+ (v'=0) transition is f00 (BH
      )=0.942. Moreover, the radiative lifetime of 38.2ns for the excited 12Pi state of
      the BH+ and 91.8ns for the 12Sigma+ state of the BH- are obtained, which are
      short enough for rapid laser cooling. A three-step optical scheme of the laser
      cooling is constructed for either the BH+ cation or the BH- anion.

PMID- 28431312
TI  - Melatonin charge transfer complex with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone:
      Molecular structure, DFT studies, thermal analyses, evaluation of biological
      activity and utility for determination of melatonin in pure and dosage forms.
AB  - A simple, accurate and fast spectrophotometric method for the quantitative
      determination of melatonin (ML) drug in its pure and pharmaceutical forms was
      developed based on the formation of its charge transfer complex with 2,3-dichloro
      5,6-dicyano-1,4-benzoquinone (DDQ) as an electron acceptor. The different
      conditions for this method were optimized accurately. The Lambert-Beer's law was
      found to be valid over the concentration range of 4-100MUgmL-1 ML. The solid form
      of the CT complex was structurally characterized by means of different spectral
      methods. Density functional theory (DFT) and time-dependent density functional
      theory (TD-DFT) calculations were carried out. The different quantum chemical
      parameters of the CT complex were calculated. Thermal properties of the CT
      complex and its kinetic thermodynamic parameters were studied, as well as its
      antimicrobial and antifungal activities were investigated. Molecular docking
      studies were performed to predict the binding modes of the CT complex components
      towards E. coli bacterial RNA and the receptor of breast cancer mutant
      oxidoreductase.

PMID- 28431313
TI  - Raman spectroscopy for the characterization of different fractions of hemp
      essential oil extracted at 130 degrees C using steam distillation method.
AB  - In this study, Raman spectroscopy along with Principal Component Analysis (PCA)
      is used for the characterization of pure essential oil (pure EO) isolated from
      the leaves of the Hemp (Cannabis sativa L.,) as well as its different fractions
      obtained by fractional distillation process. Raman spectra of pure Hemp essential
      oil and its different fractions show characteristic key bands of main volatile
      terpenes and terpenoids, which significantly differentiate them from each other.
      These bands provide information about the chemical composition of sample under
      investigation and hence can be used as Raman spectral markers for the qualitative
      monitoring of the pure EO and different fractions containing different active
      compounds. PCA differentiates the Raman spectral data into different clusters and
      loadings of the PCA further confirm the biological origin of the different
      fractions of the essential oil.

PMID- 28431314
TI  - Effect of metals on microcystin abundance and environmental fate.
AB  - Metals can react with microcystin (MC), which is released from cyanobacterial
      blooms through various mechanisms; these reactions may mitigate the environmental
      and health risks of MCs but may also cause harm to aquatic ecosystems and humans.
      Several studies were conducted, including laboratory tests, ecological
      simulations, and a field investigation of Poyang Lake. The laboratory studies
      showed that Fe3+, Cu2+, and Pb2+ stimulated MC photodegradation under high light
      intensity at the water-sediment interface, which reduced the MC accumulation in
      the sediment. In the laboratory studies involving the addition of metal ions to
      lake sediment containing adsorbed MC, MC biodegradation was inhibited by
      supplementing with high levels of Fe3+, Cu2+, or Pb2+. Fe3+ and Pb2+ promoted MC
      accumulation in the hydrophyte Eichhornia crassipes at relatively low
      concentrations, but this effect decreased with increasing high metal
      concentrations. An ecological survey in Poyang Lake during the dry season
      demonstrated that high Fe levels can reduce MC accumulation in the sediment,
      which could be the result of Fe-mediated photodegradation. The results indicate
      that metals involved in MC transportation and degradation may play an important
      role in the environmental fate of MC.

PMID- 28431315
TI  - Effects of PM2.5 exposure on the Notch signaling pathway and immune imbalance in
      chronic obstructive pulmonary disease.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes
      subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role
      in the development of the adaptive immunity. The immune disorder induced by fine
      particulate matter (PM2.5) is related to COPD. The aim of this study was to
      investigate the mechanism by which PM2.5 influences the Notch signaling pathway
      leading to worsening immune disorder and accelerating COPD development. A COPD
      mouse model was established by cigarette smoke exposure. PM2.5 exposure was
      performed by aerosol inhalation. gamma-secretase inhibitor (GSI) was given using
      intraperitoneal injection. Splenic T lymphocytes were purified using a density
      gradient centrifugation method. CD4+ T lymphocyte subsets (Th1/Th2, Th17/Treg)
      were detected using flow cytometry. mRNA and proteins of Notch1/2/3/4, Hes1/5,
      and Hey1 were detected using RT-PCR and Western blot. Serum INF-gamma, IL-4, IL
      17 and IL-10 concentrations were measured using ELISA. The results showed that in
      COPD mice Th1% and Th17%, Th1/Th2 and Th17/Treg were increased, and the levels of
      mRNA and protein in Notch1/2/3/4, Hes1/5, and Hey1 and serum INF-gamma and IL-17
      concentrations were significantly increased, and Th2%, Treg%, and serum IL-4 and
      IL-10 concentrations were significantly decreased. COPD Mice have Th1- and Th17
      mediated immune disorder, and the Notch signaling pathway is in an overactivated
      state. PM2.5 promotes the overactivation of the Notch signaling pathway and
      aggravates the immune disorder of COPD. GSI can partially inhibit the activation
      of the Notch signaling pathway and alleviate the immune disorder under basal
      state and the immune disorder of COPD caused by PM2.5. This result suggests that
      PM2.5 is involved in the immune disorder of mice with COPD by affecting the Notch
      signaling pathway and that PM2.5 aggravates COPD.

PMID- 28431316
TI  - PBDEs (polybrominated diphenyl ethers) pose a risk to captive giant pandas.
AB  - The Qinling subspecies of giant panda (Ailuropoda melanoleuca qinlingensis), is
      highly endangered; fewer than 350 individuals still inhabit Qinling Mountains.
      Previous research revealed captive pandas were exposed to bromine, so we
      hypothesized that captive pandas were exposed to and affected by polybrominated
      diphenyl ethers (PBDEs). To test this hypothesis, we tested blood and feces of
      captive and wild pandas, their drinking water, food (bamboo leaves) from SWARC
      (Shaanxi Wild Animal Research Center)and FNNR (Foping National Nature Reserve)
      and supplemental feedstuff given to captive panda at SWARC. We found 13 congeners
      of PBDEs in fecal samples, of which BDE47, BDE66, BDE71, BDE99, and BDE154 were
      the dominant, total PBDE concentration in feces of captive pandas was 255% higher
      than in wild pandas. We found nine PBDEs congeners in blood samples: BDE153 and
      BDE183 were the predominant congers. PBDEs in blood from captive pandas were
      significantly higher than in wild pandas. The total concentration of PBDEs were
      5473 and 4835 (pg.g) in Fargesia qinlingensis, were 2192 and 1414 (pg.g) in
      Bashannia fargesii (2192, 1414 pg g), 0.066, 0.038 (pg/ml) in drinking water, and
      28.8 (pg.g) in supplemental feedstuff for captive and wild pandas, which indicate
      that the PBDEs came from its bamboo feed, especially from Bashannia fargesii. Our
      results demonstrate that BDE99 and BDE47 could be threatening the pandas' health
      especially for captive panda and there are potential health risks from PBDEs for
      pandas. In the short term, this risk may be ameliorated by strict control of food
      quality. In the long term, however, reducing air, water and soil contamination so
      as to improve environmental quality can best reduce these risks to meet the
      international standard such as Stockholm Convention.

PMID- 28431317
TI  - Ambient PM2.5 exposure and premature mortality burden in the holy city Varanasi,
      India.
AB  - More than 3 million population residing in the holy city Varanasi and sub-urban
      areas is exposed to very high level of fine particulate matter (PM2.5) from
      various sources. Continuous monitoring by Central Pollution Control Board started
      only in 2015; therefore what was the pollution level in the past and how it has
      changed over the years are not known. We use MODIS aerosol products to infer
      PM2.5 and examine 15-year climatology. Data shows a rapid (1.5-3% per year)
      increase in PM2.5 in the last 15 years and high (87% days in a year) persistence
      of PM2.5 above the national air quality standard. It translates to a burden of
      5700 (2800-7500) annual premature deaths (0.16% of the population), of which 29%,
      18%, 33%, 19% and remaining 1% are attributed to ischemic heart disease, stroke,
      chronic obstructive pulmonary disease, acute lower respiratory infection and lung
      cancer respectively. If the region achieves the Indian (WHO) air quality
      standard, 1900 (3800) premature deaths can be avoided every year.

PMID- 28431319
TI  - Response of plasma glucagon-like peptide-2 to feeding pattern and intraruminal
      administration of volatile fatty acids in sheep.
AB  - Glucagon-like peptide-2 (GLP-2), a gut peptide secreted by enteroendocrine L
      cells, has recently been identified as a key regulator of intestinal growth and
      absorptive function in ruminants. However, reports on GLP-2 secretion are few,
      and more information regarding its secretion dynamics is needed. In this study,
      two experiments were conducted to elucidate the daily rhythm of GLP-2 secretion
      in response to feeding regimen and to investigate the effect of volatile fatty
      acids (VFA) on GLP-2 release in sheep. In experiment 1, blood samples were
      collected over 3 d from 4 Suffolk mature wethers adapted to a maintenance diet
      fed once daily; day 1 sampling was preceded by 24 h of fasting to reach steady
      state. On days 1 and 3, samples were collected every 10 min from 11:00 to 14:00
      on both days and then every 1 h until 00:00 on day 1 only; feed was offered at
      12:00. On day 2, feed was withheld, and sampling was performed every hour from
      01:00 to 00:00. In experiment 2, 5 Suffolk mature wethers were assigned to 5
      treatment groups of intraruminal administration of saline, acetate, propionate,
      butyrate, or VFA mix (acetate, propionate, and butyrate in a ratio of 65:20:15)
      in a 5 * 5 Latin square design. Blood samples were collected at 0, 1.5, 3, 6, 9,
      12, 15, 20, 25, 30, 40, 50, 60, 90, and 120 min relative to the beginning of
      administration at 12:00. In both experiments, plasma GLP-2, glucagon-like peptide
      1 (GLP-1), glucose, insulin, and beta-hydroxy butyric acid (BHBA) levels were
      measured. In experiment 1, incremental area under the curve was greater (P <
      0.05) post-feeding than pre-feeding on days 1 and 3 for GLP-2 and tended to be
      greater (P < 0.1) on day 1 for GLP-1. Plasma insulin, glucose, and BHBA levels
      increased (P < 0.05) on day 1 post-feeding. Plasma GLP-2 was poorly correlated
      with GLP-1 but positively correlated with insulin, glucose, and BHBA. In
      experiment 2, administration of butyrate and VFA mix remarkably increased plasma
      GLP-2 (P = 0.05) and BHBA (P < 0.0001) levels compared with those in other
      treatments. Plasma GLP-1 levels were higher with butyrate administration compared
      with those in the saline, acetate, and VFA mix (P = 0.019). Propionate
      administration increased plasma glucose (P = 0.013) and insulin (P = 0.053)
      levels. Thus, our data confirmed that GLP-2 release is responsive to feeding and
      might be promoted by BHBA produced by the rumen epithelial metabolism of
      butyrate. Further molecular- and cellular-level studies are needed to determine
      the role of butyrate as a signaling molecule for GLP-2 release.

PMID- 28431318
TI  - Assessing seasonal variation of synthetic musks in beach sands from Oporto
      coastal area: A case study.
AB  - Synthetic musk compounds are widely used in the formulation of several cosmetics,
      personal care and household products. Due to their massive and widespread use,
      together with some health concerns, they are considered emerging pollutants and
      have been detected in different environmental compartments. This study focused on
      the evaluation of the concentration of synthetic musks (five nitro, five
      polycyclic and one macrocyclic musks) in beach sands, from Oporto coastal area
      (Portugal), contributing to the enhancement of the knowledge of levels, trends
      and behaviour of these compounds in this particular matrix. To accomplish this
      task, a QuEChERS methodology ("Quick, Easy, Cheap, Effective, Rugged, and Safe")
      coupled to gas chromatography-mass spectrometry (GC-MS) was successfully used to
      determine synthetic musks from beach sand. The chosen methodology proved to be
      suitable, achieving satisfactory results for precision (relative standard
      deviation values below 15%), accuracy (average recovery of 97%) and limits of
      detection (below 38 pg g-1). Synthetic musks were detected in all 45 analysed
      samples, in concentrations ranging from 0.01 to 27 ng g-1dw. Tonalide (93%),
      exaltolide (89%) and galaxolide (76%) were the most commonly detected compounds,
      but also those detected in higher concentrations (up to 27 ng g-1dw). Musk
      ambrette, moskene, tibetene and xylene were not detected in any of the samples.
      Higher concentrations were as expected detected in the Summer (total average
      concentration of 9.21 ng g-1dw), namely in samples from Valadares Sul (29 ng g
      1dw), Francelos (25 ng g-1dw) and Castelo do Queijo (25 ng g-1dw). The
      preliminary environmental risk assessment study based on the determination of
      hazard quotients revealed that the presence of analysed compounds (tonalide,
      galaxolide and musk ketone) seems to pose no risk to the studied environmental
      compartment.

PMID- 28431320
TI  - Trehalose supplementation reduces hepatic endoplasmic reticulum stress and
      inflammatory signaling in old mice.
AB  - The accumulation of damaged proteins can perturb cellular homeostasis and provoke
      aging and cellular damage. Quality control systems, such as the unfolded protein
      response (UPR), inflammatory signaling and protein degradation, mitigate the
      residence time of damaged proteins. In the present study, we have examined the
      UPR and inflammatory signaling in the liver of young (~6 months) and old (~28
      months) mice (n=8/group), and the ability of trehalose, a compound linked to
      increased protein stability and autophagy, to counteract age-induced effects on
      these systems. When used, trehalose was provided for 4 weeks in the drinking
      water immediately prior to sacrifice (n=7/group). Livers from old mice were
      characterized by activation of the UPR, increased inflammatory signaling and
      indices of liver injury. Trehalose treatment reduced the activation of the UPR
      and inflammatory signaling, and reduced liver injury. Reductions in proteins
      involved in autophagy and proteasome activity observed in old mice were restored
      following trehalose treatment. The autophagy marker, LC3B-II, was increased in
      old mice treated with trehalose. Metabolomics analyses demonstrated that
      reductions in hexosamine biosynthetic pathway metabolites and nicotinamide in old
      mice were restored following trehalose treatment. Trehalose appears to be an
      effective intervention to reduce age-associated liver injury and mitigate the
      need for activation of quality control systems that respond to disruption of
      proteostasis.

PMID- 28431321
TI  - Atherogenicity of amino acids in the lipid-laden macrophage model system in vitro
      and in atherosclerotic mice: a key role for triglyceride metabolism.
AB  - Atherosclerosis-related research has focused mainly on the effects of lipids on
      macrophage foam cell formation and atherogenesis, whereas the role of amino acids
      (AAs) was understudied. The current study aimed to identify anti- or pro
      atherogenic AA in the macrophage model system and to elucidate the underlying
      metabolic and molecular mechanisms. J774A.1 cultured macrophages were treated
      with increasing concentrations of each 1 of the 20 AAs. Macrophage atherogenicity
      was assessed in terms of cellular toxicity, generation of reactive oxygen species
      (ROS) and cellular cholesterol or triglyceride content. At nontoxic
      concentrations (up to 1 mM), modest effects on ROS generation or cholesterol
      content were noted, but six specific AAs significantly affected macrophage
      triglyceride content. Glycine, cysteine, alanine and leucine significantly
      decreased macrophage triglyceride content (by 24%-38%), through attenuated uptake
      of triglyceride-rich very low-density lipoprotein (VLDL) by macrophages. In
      contrast, glutamate and glutamine caused a marked triglyceride accumulation in
      macrophages (by 107% and 129%, respectively), via a diacylglycerol
      acyltransferase-1 (DGAT1)-dependent increase in triglyceride biosynthesis rate
      with a concurrent maturation of the sterol regulatory element-binding protein-1
      (SREBP1). Supplementation of apolipoprotein E-deficient (apoE-/-) mice with
      glycine for 40 days significantly decreased the triglyceride levels in serum and
      in peritoneal macrophages (MPMs) isolated from the mice (by 19%). In contrast,
      glutamine supplementation significantly increased MPM ROS generation and the
      accumulation of cholesterol and that of triglycerides (by 48%), via enhanced
      uptake of LDL and VLDL. Altogether, the present findings reveal some novel roles
      for specific AA in macrophage atherogenicity, mainly through modulation of
      cellular triglyceride metabolism.

PMID- 28431322
TI  - Xanthohumol and 8-prenylnaringenin ameliorate diabetic-related metabolic
      dysfunctions in mice.
AB  - Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by metabolic
      disturbances in specific tissues. The present work aimed to analyze the effects
      of xanthohumol (XN) and 8-prenylnaringenin (8PN), two beer-derived polyphenols,
      in liver and skeletal muscle lipid and glycolytic metabolism in T2DM mice model.
      Thirty C57Bl/6 mice were randomly divided into five groups: standard diet
      (control), high-fat diet (DM), high-fat diet plus ethanol (DM-Ethanol), high-fat
      diet plus 10 mg/L XN (DM-XN) and high-fat diet plus 10 mg/L 8PN (DM-8PN) during
      20 weeks. Fasting blood glucose and insulin tolerance tests were performed 1 week
      before sacrifice. At the end of the study, blood, liver and skeletal muscle were
      collected. Both XN and 8PN treatments prevented body weight gain; decreased
      glycemia, triglyceride, cholesterol and alkaline phosphatase levels; and improved
      insulin sensitivity. Polyphenols promoted hepatic and skeletal muscle AMP
      activated protein kinase (AMPK) activation, diminishing the expression of target
      lipogenic enzymes (sterol regulatory element binding protein-1c and fatty acid
      synthase) and acetyl-CoA carboxylase activity. Moreover, both XN and 8PN
      treatments decreased VEGFR-1/VEGFB pathway, involved in fatty acid uptake, and
      increased AS160 expression, involved in GLUT4 membrane translocation. Presented
      data demonstrated that both XN and 8PN treatment resulted in AMPK signaling
      pathway activation, thus suppressing lipogenesis. Their consumption prevented
      body weight gain and improved plasma lipid profile, with significant improvement
      of insulin resistance and glucose tolerance. XN- or 8PN-enriched diet could
      ameliorate diabetic-associated metabolic disturbances by regulating glucose and
      lipid pathways.

PMID- 28431324
TI  - Achievable separation performance and analysis time in current liquid
      chromatographic practice for monoclonal antibody separations.
AB  - The separation performance of a chromatographic system is often described in
      terms of column efficiency and peak capacity. Thanks to the new developments in
      column technology over the past few years, the achievable peak capacity
      drastically improved and the analysis time can be significantly shortened.
      Indeed, highly efficient wide-pore reversed-phase (RPLC) materials packed with
      small fully porous and superficially porous particles can be successfully used
      for the analytical characterization of therapeutic proteins. For non denaturating
      chromatographic approaches, such as ion exchange (IEX) and size-exclusion
      chromatography (SEC), non-porous ion-exchanger as well as sub -3MUm size
      exclusion supports are commercially available and open new avenues in protein
      separations. In this study, the current possibilities offered by chromatography
      for the characterization of monoclonal antibody (mAb) are discussed. For this
      purpose, recently published data have been reviewed and calculations were
      performed to compare the maximum achievable peak capacity and related analysis
      times using typical samples under RPLC, IEX and SEC conditions. Carefully chosen
      realistic column pressure, mobile phase temperature, flow rate and column
      dimensions were considered for the case studies discussed through the paper.

PMID- 28431323
TI  - Transcranial magnetic stimulation in developmental stuttering: Relations with
      previous neurophysiological research and future perspectives.
AB  - Developmental stuttering (DS) is a disruption of the rhythm of speech, and
      affected people may be unable to execute fluent voluntary speech. There are still
      questions about the exact causes of DS. Evidence suggests there are differences
      in the structure and functioning of motor systems used for preparing, executing,
      and controlling motor acts, especially when they are speech related. Much
      research has been obtained using neuroimaging methods, ranging from functional
      magnetic resonance to diffusion tensor imaging and
      electroencephalography/magnetoencephalography. Studies using transcranial
      magnetic stimulation (TMS) in DS have been uncommon until recently. This is
      surprising considering the relationship between the functionality of the motor
      system and DS, and the wide use of TMS in motor-related disturbances such as
      Parkinson's Disease, Tourette's Syndrome, and dystonia. Consequently, TMS could
      shed further light on motor aspects of DS. The present work aims to investigate
      the use of TMS for understanding DS neural mechanisms by reviewing TMS papers in
      the DS field. Until now, TMS has contributed to the understanding of the
      excitatory/inhibitory ratio of DS motor functioning, also helping to better
      understand and critically review evidence about stuttering mechanisms obtained
      from different techniques, which allowed the investigation of cortico-basal
      thalamo-cortical and white matter/connection dysfunctions.

PMID- 28431325
TI  - BFGF neutralization stimulates VEGF secretion in melanoma B16 cells.
AB  - Fusarium root rot is a major cryptogamic disease in olive trees caused by the
      soil-borne fungus Fusarium solani.Controlling this disease requires the extensive
      use of chemicals. However, using BCAs such as some Trichodermastrains may be an
      opportune alternative to fungicides in protecting olive plantations. A new
      isolate (Fso14) wasisolated from young olive trees showing severe dieback
      symptoms. The objective of this work was to analyze thebiocontrol behavior of a
      Tunisian strain of T. harzianum (Ths97) on olive trees against Fso14 by assessing
      bothmycoparasitic activity (in planta and in vitro) and ability to locally
      modulate different gene-related defenses ofthe plant. Ths97 was found to inhibit
      Fso14 growth in vitro. Optical microscopic analysis at the confrontationzone
      between hyphae showed that Ths97 grew alongside Fso14 with numerous contact
      points suggestingparasitic activity. On olive trees, Ths97 developed a strong
      protective role against root infestation by Fso14,whether inoculated before or
      after the pathogenic agent. When inoculated alone, Fso14 and Ths97 did
      notmodulate (or only slightly with inhibitions or inductions, respectively) the
      expression of genes involved in plantimmunity (oxidative stress, phenylpropanoid
      pathway, PR-proteins and JA/Et-SA hormonal status). However,when Ths97 was
      inoculated in combination with Fso14, several defense-related genes were highly
      up-regulated,indicating probable primed-plant events. These promising results
      provided valuable information on using Ths97as a beneficial agent to control
      fusarium root rot disease caused by F. solani in olive trees.

PMID- 28431326
TI  - Incidentally detected splenogonadal fusion in a laparoscopic transabdominal
      preperitoneal hernia repair operation: A case report.
AB  - INTRODUCTION: Splenogonadal fusion (SGF) is a rare congenital malformation in
      which the spleen is connected to the gonad. Few SGF cases have been reported in
      the English scientific literature, and we are unaware of any previous case
      reports of SGF with inguinal hernia by laparoscopic transabdominal preperitoneal
      hernia repair (TAPP). Here, we report a case of SGF that was incidentally
      detected during a TAPP procedure, with an uneventful postoperative course without
      complications. PRESENTATION OF CASE: A 76-year-old male presented with a 10-year
      history of left inguinal swelling. He was diagnosed with a left inguinal hernia,
      and we performed TAPP. Laparoscopy revealed the left inguinal hernia and two
      reddish-purple masses, one located close to the left inguinal ring. A cord of
      soft tissue extended cranially from the mass to the spleen, and passed through
      the left internal inguinal ring caudally. We cut the cord for mesh placement and
      to make an accurate diagnosis of the mass. Pathological and intraoperative
      findings indicated a diagnosis of continuous SGF. DISCUSSION: We observed two
      important clinical issues in this case. First, the potential for incidental
      diagnoses of SGF may be increasing. Second, to our knowledge, this is the first
      case report of a patient with SGF identified by TAPP. Such a therapeutic strategy
      for incidentally detected SGF has not been described; here we report a successful
      experience. CONCLUSION: To our knowledge, this is the first report of a patient
      with SGF diagnosed by a TAPP procedure. The postoperative course was uneventful
      using our method.

PMID- 28431327
TI  - Dendrimer-conjugated iron oxide nanoparticles as stimuli-responsive drug carriers
      for thermally-activated chemotherapy of cancer.
AB  - In recent years, functional nanomaterials have found an appreciable place in the
      understanding and treatment of cancer. This work demonstrates the fabrication and
      characterization of a new class of cationic, biocompatible, peptide dendrimers,
      which were then used for stabilizing and functionalizing magnetite nanoparticles
      for combinatorial therapy of cancer. The synthesized peptide dendrimers have an
      edge over the widely used PAMAM dendrimers due to better biocompatibility and
      negligible cytotoxicity of their degradation products. The surface engineering
      efficacy of the peptide dendrimers and their potential use as drug carriers were
      compared with their PAMAM counterparts. The peptide dendrimer was found to be as
      efficient as PAMAM dendrimers in its drug-carrying capacity, while its drug
      release profiles substantially exceeded those of PAMAM's. A dose-dependent study
      was carried out to assess their half maximal inhibitory concentration (IC50) in
      vitro with various cancer cell lines. A cervical cancer cell line that was
      incubated with these dendritic nanoparticles was exposed to alternating current
      magnetic field (ACMF) to investigate the effect of elevated temperatures on the
      live cell population. The DOX-loaded formulations, in combination with the ACMF,
      were also assessed for their synergistic effects on the cancer cells for
      combinatorial therapy. The results established the peptide dendrimer as an
      efficient alternative to PAMAM, which can be used successfully in biomedical
      applications.

PMID- 28431328
TI  - Effects of quantum dots on the ROS amount of liver cancer stem cells.
AB  - Liver cancer (LC) is a serious disease that threatens human lives. LC has a high
      recurrence rate and poor prognosis. LC stem cells (LCSCs) play critical roles in
      these processes. However, the mechanism remains unclear. Reactive oxygen species
      (ROS) can be used to determine cell apoptosis and proliferation. However, studies
      of the effects of exogenous nanomaterials on LCSC ROS changes are rarely
      reported. In this work, quantum dots (QDs) were prepared using a hydrothermal
      method, and QDs were further modified with polyethylene glycol (PEG) and bovine
      serum albumin (BSA) using a chemical approach. The effects of QDs, PEG-modified
      QDs (PEG@QDs) and BSA-modified QDs (BSA@QDs) on the amounts of ROS in liver
      cancer PLC/PRF/5 (PLC) cells and liver cancer stem cells (LCSCs) were principally
      investigated. The results showed that when the concentration of QDs, PEG@QDs, and
      BSA@QDs were 10nM and 90nM, the ROS amount in PLC cells increased by
      approximately 2- to 5-fold. However, when the concentrations of these
      nanomaterials were 10nM and 90nM, ROS levels in LCSCs were reduced by
      approximately 50%. This critical path potentially leads to drug resistance and
      recurrence of LC. This work provides an important indication for further study of
      LC drug resistance and recurrence.

PMID- 28431329
TI  - Stealth recombinant human serum albumin nanoparticles conjugating 5-fluorouracil
      augmented drug delivery and cytotoxicity in human colon cancer, HT-29 cells.
AB  - BACKGROUND AND OBJECTIVE: 5-Fluorouracil (5-FU) is a first-line chemotherapeutic
      drug in colorectal cancer. However, intravenous administration of 5-FU at the
      dose of 7-12mg/kg exhibits curbs like short half-life (20min) and toxic side
      effects on bone marrow cells. Therefore, in present investigation, 5-FU was
      conjugated to poly (ethylene glycol) anchored recombinant human serum albumin
      nanoparticles (5-FU-rHSA-PEG-NPs) to improve the pharmacokinetic and therapeutic
      profiles. METHODS AND RESULTS: The mean particle size of 5-FU-rHSA-NPs was
      measured to be 44.3+/-5.8-nm, significantly (P<0.05) lesser than 65.7+/-7.2-nm of
      5-FU-rHSA-PEG-NPs. In addition, zeta-potential of 5-FU-rHSA-NPs was estimated to
      be -10.2+/-2.6-mV significantly (P<0.05) lower than -25.8+/-3.5-mV of 5-FU-rHSA
      PEG-NPs. Moreover, both 5-FU-rHSA-NPs and 5-FU-rHSA-PEG-NPs were smooth,
      spherical and regular in shape. In-vitro drug release analysis indicated that 5
      FU-rHSA-NPs and 5-FU-rHSA-PEG-NPs separately released 10.9% and 9.23% of 5-FU in
      PBS (pH~7.4) with no significant difference (P>0.05) up to 48h. However, addition
      of 20% v/v serum to PBS (pH~7.4) boosted the drug release. 5-FU-rHSA-NPs and 5-FU
      rHSA-PEG-NPs released 78.26% and 48.9% of the 5-FU up to 48h in presence of PBS
      (pH~7.4 and 20% serum) with significant difference (P<0.05). Furthermore, 5-FU
      rHSA-PEG-NPs displayed the IC50 of 3.7-MUM significantly (P<0.05) lower than 6.8
      MUM and 11.2-MUM of 5-FU-rHSA-NPs and 5-FU solution, respectively. One
      compartmental pharmacokinetic elements indicated that 5-FU-rHSA-PEG-NPs
      demonstrated the half-life (t1/2) of 5.33+/-0.15-h significantly (P<0.001) higher
      than 1.50+/-0.08-h and 0.30+/-0.09-h of 5-FU-rHSA-NPs and 5-FU solution,
      respectively. CONCLUSION: 5-FU-rHSA-PEG-NPs tendered improved cytotoxicity and
      pharmacokinetic profile. Hence, 5-FU-rHSA-PEG-NPs must be further tested under
      stringent milieu for translating in to a clinical product.

PMID- 28431330
TI  - Gas-forming liposomes prepared using a liposomal magnetoporation method.
AB  - In this study, we report a gas-forming drug carrier engineered using the
      liposomal magnetoporation method. The liposomes that were magnetoporated under a
      magnetic shear stress possessed an opened lipid bilayer hole. A photosensitizing
      model drug (chlorin e6: Ce6) and 1H-1H-2H-perfluoro-1-hexene (PFH, as a volatile
      gas-forming agent) were efficiently loaded into the opened holes of the
      magnetoporated liposomes. PFH in the liposomes is vaporized at 50 degrees C and
      can initiate liposome destabilization. The experimental results demonstrated that
      the liposomes were destabilized at 50 degrees C efficiently released Ce6 and
      enhanced Ce6-mediated phototoxicity against KB tumor cells. As a result, these
      liposomes induced a significantly increased in vitro and in vivo photodynamic
      tumor inhibition.

PMID- 28431331
TI  - Dielectric properties of a novel colloidal oral matrix drug carrier.
AB  - Dielectric Spectroscopy (DS) was employed to study a novel oral matrix carrier
      (OMC), composed from silica nano-particles, polysaccharides, biopolymers and
      natural oils. This composition self-orders to a multi hierarchal structure and as
      such is amenable to be studied by techniques such as DS. The dielectric
      properties were measured in the frequency range 1MHz-1GHz and a temperature range
      10 degrees C-45 degrees C. The results were dominated by two relaxation processes
      following CC relaxation and having relaxation times that are Arrhenius in nature.
      These processes can be traced to structural elements in the OMC and are
      influenced by the melting point of coconut oil, an essential element in the
      formulation. Furthermore, the correlations between dipolar entities in the OMC
      are investigated using Froelich's B function formulation. The results point to DS
      as an effective tool for the study of these systems.

PMID- 28431332
TI  - Sperm morphology of the leafhopper Diaphorina citri Kuwayama (Hemiptera:
      Sternorrhyncha: Psylloidea: Liviidae).
AB  - In this study, by using light and electron microscopy, we describe the sperm
      morphology of the leafhopper Diaphorina citri, a serious pest of citrus
      throughout the world. In this species the sperm measures 538.49+/-8.75MUm in
      length, and as observed in psylloids, the sperm, when manipulated, opens into two
      filaments, one of which is attached to the nuclear base and the other becomes
      free. Along the flagellum, and only of it, there are lateral projections, about
      2MUm in length. Furthermore, at the end of the flagellum three appendages, with
      approximately 7MUm in length, are observed. The head region is formed by the
      nucleus with compact chromatin, and, parallel to it, a structure of median
      electron density that extends about 25MUm in length ahead of the nuclear tip. The
      flagellum consists of an axoneme with a 9+9+2 microtubule arrangement, two
      mitochondrial derivatives, and two accessory bodies each with two regions of
      different electron density. The presence of lateral projections is a
      characteristic observed in other Sternorrhyncha. As seen previously, the sperm
      opening in two filaments, when manipulated, was observed only in Psylloidea, and
      the presence of the three appendices at the end of the flagellum distinguishes D.
      citri from the other Psylloidea species studied.

PMID- 28431333
TI  - Regeneration and health: a structured, rapid literature review.
AB  - OBJECTIVE: To identify and synthesise what is known about the impacts of
      regeneration on health, health inequalities and their socio-economic
      determinants. STUDY DESIGN: Rapid, structured literature review. METHODS: A
      rapid, structured approach was undertaken to identifying relevant studies
      involving a search of peer-reviewed literature databases, an Internet search to
      identify relevant grey literature, and a review of articles citing two key
      systematic reviews. The identified citations were screened, critically appraised
      according to the research design and narratively synthesised. RESULTS: Of the
      1382 identified citations, 46 were screened as relevant to the review and
      included in the synthesis. Fifteen citations were reviews but most of the
      evidence identified or included within the reviews was of medium or low quality
      due to a lack of longitudinal follow-up, low response rates or attrition. The
      evidence base on the impacts of regeneration is generally not of high quality and
      is prone to bias. However, it is theorised as being an important means of
      addressing the socio-economic determinants of health. Housing refurbishment
      (generally, and for specific improvements) seems likely to lead to small
      improvements in health, whereas rehousing and mixed-tenure approaches have less
      clear impacts on health and carry risks of disruption to social networks and
      higher rents. Changes in the social composition of communities (gentrification)
      is a common outcome of regeneration and some 'partnership' approaches to
      regeneration have been shown to have caused difficulties within communities.
      CONCLUSIONS: The evidence base for regeneration activities is limited but they
      have substantial potential to contribute to improving population health. Better
      quality evidence is available for there being positive health impacts from
      housing-led regeneration programmes involving refurbishment and specific housing
      improvements. There is also some evidence of the potential harms of regeneration
      activities, including social stratification (gentrification and residualisation)
      and the destabilisation of existing community organisations. Broader labour
      market and housing policy approaches are also likely to be important as a context
      for understanding impacts. Regeneration programmes require careful design,
      implementation and evaluation if they are to contribute to improved health and
      reduced health inequalities.

PMID- 28431334
TI  - One hundred injured patients a day: multicenter emergency room surveillance of
      trauma in Pakistan.
AB  - OBJECTIVES: Injuries increasingly contribute to the global burden of disease in
      low- and middle-income countries. This study presents results from a large-scale
      surveillance study on injury from several urban emergency departments (EDs) in
      Pakistan. The objective is to document the burden of injuries that present to the
      healthcare system in Pakistan and to test the feasibility of an ED-based injury
      and trauma surveillance system. STUDY DESIGN: Cross-sectional study conducted
      using active surveillance approach. METHODS: This study included EDs of seven
      tertiary care hospitals in Pakistan. The data were collected between November
      2010 and March 2011. All patients presenting with injuries to the participating
      EDs were enrolled. The study was approved by the Institutional Review Boards of
      the Johns Hopkins School of Public Health, Aga Khan University, and all
      participating sites. RESULTS: The study recorded 68,390 patients; 93.8% were from
      the public hospitals. There were seven male for every three female patients, and
      50% were 20-39 years of age. About 69.3% were unintentional injuries. Among
      injuries with a known mechanism (19,102), 51.1% were road traffic injuries (RTIs)
      and 17.5% were falls. Female, patients aged 60 years or older, patients
      transferred by ambulance, patients who had RTIs, and patients with intentional
      injuries were more likely to be hospitalized. CONCLUSION: The study is the first
      to use standardized methods for regular collection of multiple ED data in
      Pakistan. It explored the pattern of injuries and the feasibility to develop and
      implement facility-based systems for injury and acute illness in countries like
      Pakistan.

PMID- 28431335
TI  - Minimization of the amount of Kryptofix 222 - KHCO3 for applications to
      microscale 18F-radiolabeling.
AB  - Conversion of aqueous [18F]fluoride to reactive [18F]fluoride is an important
      first step in the radiosynthesis of 18F-labeled compounds by nucleophilic
      substitution. A versatile method for the rapid preparation of reactive
      [18F]fluoride by the combined use of an Oasis MAX cartridge and a methanolic
      solution of the Kryptofix 222-KHCO3 complex (K.222/KHCO3) was developed. The
      latter amount was optimized with the aim to keep it as low as possible while
      achieving recovery yields of [18F]fluoride comparable to those attained with the
      commonly used QMA cartridge. Thus, a 97% recovery yield was obtained with just
      2umol of K.222/KHCO3 methanolic solution (10mM, 200uL) within 7min. This result
      allowed in turn to optimize the microscale radiosynthesis of [18F]FDG. Moreover,
      the method was successfully applied to the 100uL-scale 18F-substitution reactions
      of several precursors.

PMID- 28431336
TI  - Beam-induced back-streaming electron suppression analysis for an accelerator type
      neutron generator designed for 40Ar/39Ar geochronology.
AB  - A facility based on a next-generation, high-flux D-D neutron generator has been
      commissioned and it is now operational at the University of California, Berkeley.
      The current generator designed for 40Ar/39Ar dating of geological materials
      produces nearly monoenergetic 2.45MeV neutrons at outputs of 108n/s. The narrow
      energy range is advantageous relative to the 235U fission spectrum neutrons due
      to (i) reduced 39Ar recoil energy, (ii) minimized production of interfering argon
      isotopes from K, Ca, and Cl, and (iii) reduced total activity for radiological
      safety and waste generation. Calculations provided show that future conditioning
      at higher currents and voltages will allow for a neutron output of over 1010n/s,
      which is a necessary requirement for production of measurable quantities of 39Ar
      through the reaction 39K(n,p)39Ar. A significant problem encountered with
      increasing deuteron current was beam-induced electron backstreaming. Two methods
      of suppressing secondary electrons resulting from the deuterium beam striking the
      target were tested: the application of static electric and magnetic fields.
      Computational simulations of both techniques were done using a finite element
      analysis in COMSOL Multiphysics(r). Experimental tests verified these
      simulations. The most reliable suppression was achieved via the implementation of
      an electrostatic shroud with a voltage offset of -800V relative to the target.

PMID- 28431337
TI  - A possible approach to 14MeV neutron moderation: A preliminary study case.
AB  - Deuterium-Tritium (D-T) interactions produce almost monochromatic neutrons with
      about 14MeV energy. These neutrons are used in benchmark experiments as well as
      for neutron cross sections assessment in fusion reactors technology. The
      possibility to moderate 14MeV neutrons for purposes beyond fusion is worth to be
      studied in relation to projects of intense D-T sources. In this preliminary
      study, carried out using the MCNP Monte Carlo code, the moderation of 14MeV
      neutrons is approached foreseeing the use of combination of metallic materials as
      pre-moderator and reflectors coupled to standard water moderators.

PMID- 28431338
TI  - The design and fabrication of beta sensor system for in situ diffusion tests in
      mudstone in France.
AB  - Long term in situ diffusion experiments in the Callovian-Oxfordian mudstone
      (France) are designed in the context of nuclear waste management. beta-emitters
      HTO and 36Cl radiotracers are representative of neutral and anionic species in
      these experiments. Studies have been carried out to design an in situ beta
      monitoring system in order to quantify tracer migration in the rock pore water
      over time. The development, design and calibration of beta-emitter radiation
      sensors were performed. An optimised geometry was calculated for the detection
      chamber of 36Cl in solution (O*L=30*2mm2) via Monte-Carlo N-Particle transport
      simulation tools. A better SNR (Signal to Noise Ratio) was obtained with YSO
      cylindrical crystal (O*L=6.5*0.5mm2). A sensitivity of 0.21cpm/Bq/mL was measured
      using 36Cl standards. The 36Cl detection limits were 18Bq/mL and 14.2Bq/mL after
      1h and 24h of accumulation time respectively. Such beta sensors, placed 350mm
      from the radiotracer injection borehole, could successfully discriminate 36Cl
      anisotropic diffusion in various directions within 4 years. It will be tested in
      situ and can be adapted to other in situ experience.

PMID- 28431339
TI  - Novel coumarin- and quinolinone-based polycycles as cell division cycle 25-A and 
      C phosphatases inhibitors induce proliferation arrest and apoptosis in cancer
      cells.
AB  - Cell division cycle phosphatases CDC25 A, B and C are involved in modulating cell
      cycle processes and are found overexpressed in a large panel of cancer typology.
      Here, we describe the development of two novel quinone-polycycle series of CDC25A
      and C inhibitors on the one hand 1a-k, coumarin-based, and on the other 2a-g,
      quinolinone-based, which inhibit either enzymes up to a sub-micro molar level and
      at single-digit micro molar concentrations, respectively. When tested in six
      different cancer cell lines, compound 2c displayed the highest efficacy to arrest
      cell viability, showing in almost all cell lines sub-micro molar IC50 values, a
      profile even better than the reference compound NCS95397. To investigate the
      putative binding mode of the inhibitors and to develop quantitative structure
      activity relationships, molecular docking and 3-D QSAR studies were also carried
      out. Four selected inhibitors, 1a, 1d, 2a and 2c have been also tested in A431
      cancer cells; among them, compound 2c was the most potent one leading to cell
      proliferation arrest and decreased CDC25C protein levels together with its
      splicing variant. Compound 2c displayed increased phosphorylation levels of
      histone H3, induction of PARP and caspase 3 cleavage, highlighting its
      contribution to cell death through pro-apoptotic effects.

PMID- 28431340
TI  - First macrocyclic 3rd-generation ALK inhibitor for treatment of ALK/ROS1 cancer:
      Clinical and designing strategy update of lorlatinib.
AB  - Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK)
      gene rearrangements invariably develop resistance to 2nd-generation ALK
      inhibitors. Lorlatinib (PF-06463922) (6) is a 3rd-generation macrocyclic ALK-TKI
      that demonstrates many advantages over 2nd-generation ALK inhibitors. Lorlatinib
      has demonstrated decent kinase selectivity, promising pharmacokinetic profile,
      selective brain-penetration and strong antiproliferative activity in several
      ALK/ROS1-driven tumor models. The current review describes the activity spectrum,
      key events from discovery to clinical applications and the evidences that
      lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings.

PMID- 28431341
TI  - Eco-friendly synthesis of novel cyanopyridine derivatives and their anticancer
      and PIM-1 kinase inhibitory activities.
AB  - Targeting Pim-1 kinase recently proved to be profitable for conquering cancer
      proliferation. In the current study, we report the design, synthesis and
      biological evaluation of two novel series of 2-amino cyanopyridine series (5a-g)
      and 2-oxocyanopyridine series (6a-g) targeting Pim-1 kinase. All of the newly
      synthesized compounds were evaluated for their in vitro anticancer activity
      against a panel of three cell lines, namely, the liver cancer cell line (HepG2),
      the colon cancer cell line (HCT-116) and the breast cancer cell line (MCF-7).
      Most of the compounds showed good to moderate anti-proliferative activity against
      HepG2 and HCT-116 cell lines while only few compounds showed significant
      cytotoxic activity against MCF-7 cell line. Further, the Pim-1 kinase inhibitory
      activity for the two series was evaluated where most of the tested compounds
      showed marked Pim-1 kinase inhibitory activity (26%-89%). Moreover, determination
      of the IC50 values unraveled very potent molecules in the submicromolar range
      where compound 6c possessed an IC50 value of 0.94 MUM. Moreover, apoptosis
      studies were conducted on the most potent compound 6c to evaluate the
      proapoptotic potential of our compounds. Interestingly, it induced the level of
      active caspase 3 and boosted the Bax/Bcl2 ratio 22704 folds in comparison to the
      control. Finally, a molecular docking study was conducted to reveal the probable
      interaction with the Pim-1 kinase active site.

PMID- 28431342
TI  - Discovery of tetrahydrocarbazoles as dual pERK and pRb inhibitors.
AB  - The extracellular signal-regulated kinase (ERK) is one of the most important
      molecular targets for cancer that controls diverse cellular processes such as
      proliferation, survival, differentiation and motility. Similarly, the Rb
      (retinoblastoma protein) is a tumor suppressor protein and its function is to
      prevent excessive cell growth by inhibiting cell cycle progression. When the cell
      is ready to divide, pRb is phosphorylated, becomes inactive and allows cell cycle
      progression. Herein, we discovered a new series of tetrahydrocarbazoles as dual
      inhibitors of pERK and pRb phosphorylation. The in-house small molecule library
      was screened for inhibition of pERK and pRb phosphorylation, which led to the
      discovery of tetrahydrocarbazole series of compounds as potential leads. N-(3
      methylcyclopentyl)-6-nitro-2,3,4,4a,9,9a-hexahydro-1H-carbazol-2-amine (1) is the
      dual inhibitor lead identified through screening, displaying inhibition of pERK
      and pRb phosphorylation with IC50 values of 5.5 and 4.8 MUM, respectively. A
      short structure-activity relationship (SAR) study has been performed, which
      identified another dual inhibitor 9-methyl-N-(4-methylbenzyl)-2,3,4,4a,9,9a
      hexahydro-1H-carbazol-2-amine (16) with IC50 values 4.4 and 3.5 MUM for
      inhibition of pERK and pRb phosphorylation, respectively. This compound has a
      potential for further lead optimization to discover promising molecularly
      targeted anticancer agents.

PMID- 28431343
TI  - Measurement of physical activity levels in the Intensive Care Unit and functional
      outcomes: An observational study.
AB  - PURPOSE: Primary aims were: (1) objectively quantify levels of physical activity
      with the sensewear armband mini-fly motion sensor (SWA-MF), (2) evaluate the
      correlation of SWA-MF measurement of active and resting energy expenditure
      against the ICU Mobility scale (IMS) and indirect calorimetry respectively.
      MATERIALS AND METHODS: Adults mechanically ventilated >=48h and anticipated to
      remain in ICU>=5days were included. Physical activity (PA) was measured using a
      SWA-MF (over the first five days); energy expenditure was measured with both the
      SWA-MF and the Deltatrac II metabolic cart on day three; highest level of
      mobility was assessed on the IMS. RESULTS: Fifty-five participants performed
      median [IQR] 16.8 [0.6-152.4] minutes of PA per day (defined as >1.0 metabolic
      equivalent). A strong correlation between active energy expenditure and highest
      level of mobility (IMS), r=0.76, p=0.00 was observed on day 5. The SWA-MF
      demonstrated moderate to good agreement with the Deltatrac II metabolic cart
      (n=20), intra-class correlation co-efficient=0.71 (p=0.00) for the measurement of
      energy expenditure on day 3. CONCLUSIONS: Participants demonstrated low levels of
      PA. Motion sensors may be a promising non-invasive measure of energy expenditure
      and further investigation is warranted.

PMID- 28431344
TI  - Novelty helmet use and motorcycle rider fatality.
AB  - OBJECTIVES: To compare the risk of fatal injury across helmet types among
      collision-involved motorcyclists. METHODS: We used data from a cohort of
      motorcyclists involved in police-reported traffic collisions. Eighty-four law
      enforcement agencies in California collected detailed information on helmet and
      rider characteristics during collision investigations in June 2012 through July
      2013. Multiply-adjusted risk ratios were estimated with log-binomial regression.
      RESULTS: The adjusted fatal injury risk ratio for novelty helmets was 1.95 (95%
      CI 1.11-3.40, p 0.019), comparing novelty helmets with full-face helmets. The
      risk ratios for modular, open-face, and half-helmets, compared with full-face
      helmets, were not significant. CONCLUSIONS: A more complete understanding of the
      inadequacy of novelty helmets can be used in educational and law enforcement
      countermeasures to improve helmet use among motorcycling populations in
      California and other US states. Law enforcement approaches to mitigating novelty
      helmet use would seem attractive given that novelty helmets can be visually
      identified by law enforcement officers with sufficient training.

PMID- 28431345
TI  - Insights into targeting young male drivers with anti-speeding advertising: An
      application of the Step approach to Message Design and Testing (SatMDT).
AB  - In Australia, young drivers aged 17-25 years comprise 13% of the population yet
      account for 22% of all road deaths with young males over-represented in such
      trauma. Speeding represents a major contributing factor and advertising campaigns
      have long focused on promoting anti-speeding messages in the effort to reduce
      drivers' speeds. Positioned within a larger program of research aimed at
      developing, piloting, and evaluating a range of theoretically-informed anti
      speeding messages, the current study reports results relating to the final phase
      of the research, the evaluation. Six messages were devised in accordance with the
      guiding framework, the Step approach to Message Design and Testing ([SatMDT];
      Lewis et al., 2016) and based on the findings emerging from earlier qualitative
      and quantitative studies within the program of research. N=938 licensed drivers
      (n=455 males, 48%) aged 17-62 years completed an online survey. To ensure a
      controlled test of the persuasiveness of the message content, the messages were
      presented in an audio-based format and thus were devoid of potential confounds,
      such as images. The messages sought to address a particular belief (i.e.,
      behavioural, normative, control) and to focus either on emphasising the positive
      aspects which make speeding less likely or challenging the negative aspects which
      make speeding more likely. Thus, key to this evaluation was to test the
      persuasiveness of the message content in terms of the particular belief and focus
      it was addressing. Participants were randomly assigned to either the Control
      condition (i.e., no exposure to a message) or the Intervention condition (i.e.,
      exposed to one of the six messages presented as an audio-recorded message within
      the survey). Persuasiveness was assessed via a range of outcome measures
      including both direct (i.e., third-person perceptions, message rejection) as well
      as indirect measures (i.e., intentions, willingness to speed). Age, gender, and
      message type were independent variables (IVs), together with issue involvement as
      a covariate (or IV) in the study's analyses. Overall, positive persuasive
      effects, and a relative absence of any negative, dissuasive effects, were found
      for two messages, Glass Cars and The Lift. These messages addressed the same
      salient belief, control beliefs, with the former emphasising the factors which
      discourage speeding and the latter message challenging those factors which
      encourage speeding. The implications of the findings are discussed in terms of
      the insights they offer for the key content of future anti-speeding messages.

PMID- 28431346
TI  - Caged Gammarus as biomonitors identifying thresholds of toxic metal
      bioavailability that affect gammarid densities at the French national scale.
AB  - Bioaccumulated concentrations of toxic elements in biomonitor invertebrate
      species have already been used to successfully link metal bioavailability and
      impairments of stream macroinvertebrate communities at the scale of the
      watershed. However, implementing this empirical comparative approach at a greater
      spatial scale remains a challenge due to the diversity of biogeographical
      contexts encompassed by regional and national scales. We showed in previous
      studies that the use of standard organisms caged permits the use of a common
      biomonitor over a far greater geographical range, while limiting the influence of
      confounding factors on levels of bioavailable contamination. In this study,
      levels of Cd, Hg, Ni and Pb contamination assessed by active biomonitoring with
      caged Gammarus fossarum were compared to abundances of on-site gammarids on 94
      sites in France. Based on this national dataset of in situ bioassays, we first re
      determined bioavailable background assessment concentrations (BBACs), i.e.
      concentrations measured in caged G. fossarum indicating a significant
      bioavailable contamination, which we had previously defined at a regional scale
      for these four metallic elements. On-site gammarid abundances were retrieved from
      monitoring programs implemented by French water agencies for the evaluation of
      ecological status for the European Water Framework Directive. These abundances
      were corrected for the influence of stream physico-chemical typology in order to
      permit a reliable comparison of gammarid densities between sites at the national
      scale. Clear trends of degradation of gammarid densities with increasing levels
      of bioaccumulated concentrations were identified for three of the four elements
      (Cd, Ni and Pb). Threshold concentrations in caged organisms above which the
      numbers of free-ranging gammarids were abnormally low - namely bioavailable
      ecological assessment concentrations (BEACs) - were determined. The reliability
      and validity of the BEACs, their comparison with BBACs and their usefulness in
      terms of prioritisation of contaminants, sites in freshwater management, are
      discussed.

PMID- 28431347
TI  - Improving water quality in China: Environmental investment pays dividends.
AB  - This study highlights how Chinese economic development detrimentally impacted
      water quality in recent decades and how this has been improved by enormous
      investment in environmental remediation funded by the Chinese government. To our
      knowledge, this study is the first to describe the variability of surface water
      quality in inland waters in China, the affecting drivers behind the changes, and
      how the government-financed conservation actions have impacted water quality.
      Water quality was found to be poorest in the North and the Northeast China Plain
      where there is greater coverage of developed land (cities + cropland), a higher
      gross domestic product (GDP), and higher population density. There are
      significant positive relationships between the concentration of the annual mean
      chemical oxygen demand (COD) and the percentage of developed land use (cities +
      cropland), GDP, and population density in the individual watersheds (p < 0.001).
      During the past decade, following Chinese government-financed investments in
      environmental restoration and reforestation, the water quality of Chinese inland
      waters has improved markedly, which is particularly evident from the significant
      and exponentially decreasing GDP-normalized COD and ammonium (NH4+-N)
      concentrations. It is evident that the increasing GDP in China over the past
      decade did not occur at the continued expense of its inland water ecosystems.
      This offers hope for the future, also for other industrializing countries, that
      with appropriate environmental investments a high GDP can be reached and
      maintained, while simultaneously preserving inland aquatic ecosystems,
      particularly through management of sewage discharge.

PMID- 28431348
TI  - Evaluation of structural effects on the flocculation performance of a co-graft
      starch-based flocculant.
AB  - The molecular structure of a material substantially determines its final
      application performance. In this work, a series of starch-based flocculants with
      different charge densities and average graft chain lengths were prepared by the
      co-graft polymerization of acrylamide and [(2-methacryloyloxyethyl) trimethyl
      ammonium chloride] (St-g-PAM-co-PDMC). The flocculation performance of St-g-PAM
      co-PDMC was studied systematically at neutral pH using kaolin suspension and
      sodium humate (NaHA) aqueous solution as synthetic wastewaters. The effects of
      the two structural factors on the flocculation efficiency of the starch-based
      flocculants have been investigated. The experimental results showed that the
      charge density and average graft chain length contributed distinctly to
      flocculation performance during the removal of both kaolin particles and NaHA
      under insufficient and excessive flocculant dose conditions. The flocculation
      mechanisms of this starch-based flocculant were discussed in detail on the basis
      of the structure-activity relationship, which are significant to optimize the
      flocculation conditions and guide the development of novel high-performance
      flocculants.

PMID- 28431349
TI  - Impacts of environmental factors on arsenate biotransformation and release in
      Microcystis aeruginosa using the Taguchi experimental design approach.
AB  - Very limited information is available on how and to what extent environmental
      factors influence arsenic (As) biotransformation and release in freshwater algae.
      These factors include concentrations of arsenate (As(V)), dissolved inorganic
      nitrogen (N), phosphate (P), and ambient pH. This study conducted a series of
      experiments using Taguchi methods to determine optimum conditions for As
      biotransformation. We assessed principal effective factors of As(V), N, P, and pH
      and determined that As biotransformation and release actuate at 10.0 MUM As(V) in
      dead alga cells, the As efflux ratio and organic As efflux content actuate at 1.0
      mg/L P, algal growth and intracellular arsenite (As(III)) content actuate at 10.0
      mg/L N, and the total sum of As(III) efflux from dead alga cells actuates at a pH
      level of 10. Moreover, N is the critical component for As(V) biotransformation in
      M. aeruginosa, specifically for As(III) transformation, because N can accelerate
      algal growth, subsequently improving As(III) accumulation and its efflux, which
      results in an As(V) to As(III) reduction. Furthermore, low P concentrations in
      combination with high N concentrations promote As accumulation. Following As(V),
      P was the primary impacting factor for As accumulation. In addition, small
      amounts of As accumulation under low concentrations of As and high P were
      securely stored in living algal cells and were easily released after cell death.
      Results from this study will help to assess practical applications and the
      overall control of key environmental factors, particularly those associated with
      algal bioremediation in As polluted water.

PMID- 28431350
TI  - Characteristics and components of poly-aluminum chloride coagulants that enhance
      arsenate removal by coagulation: Detailed analysis of aluminum species.
AB  - We evaluated 51 poly-aluminum chloride (PACl) coagulants to determine the
      coagulant characteristics that were responsible for effective arsenate removal
      from contaminated river water by means of experiments involving coagulation,
      settling, and microfiltration. Some of the high-basicity PACls exhibited high
      arsenate removal percentages, particularly under alkaline conditions, and we
      investigated various relevant properties and characteristics of these high
      basicity PACls. Effective arsenate removal was correlated with the content of
      polymeric and colloidal aluminum species (Alb and Alc) in the PACls but was not
      well correlated with colloid charge or zeta potential. Multiple regression
      analysis revealed that a portion of Alb and Alc, which reacted with the ferron
      reagent during the period from 30 min to 3 h, that is, the (Al30min-3h) fraction,
      had the highest arsenate sorption capacity, followed by a colloidal aluminum
      fraction (Al>3h, which reacted with ferron at a time of >3 h). The Al30min-3h
      fraction was stable, and its arsenate sorption capacity did not decrease markedly
      with increasing pH. The Al30min-3h fraction did not correspond to the Keggin-type
      e-Al13 polycation or the delta-Al30 polycation; it is likely to be an aluminum
      polymer that is unobservable by 27Al NMR spectroscopy. Our results suggest that
      PACls with a high proportion of the Al30min-3h fraction should be used for
      enhanced arsenate removal by coagulation. A high content of the e-Al13 polycation
      or the delta-Al30 polycation was not indispensable for effective arsenate
      removal.

PMID- 28431351
TI  - Role of membrane fouling substances on the rejection of N-nitrosamines by reverse
      osmosis.
AB  - The impact of fouling substances on the rejection of four N-nitrosamines by a
      reverse osmosis (RO) membrane was evaluated by characterizing individual organic
      fractions in a secondary wastewater effluent and deploying a novel high
      performance liquid chromatography-photochemical reaction-chemiluminescence (HPLC
      PR-CL) analytical technique. The HPLC-PR-CL analytical technique allowed for a
      systematic examination of the correlation between the fouling level and the
      permeation of N-nitrosamines in the secondary wastewater effluent and synthetic
      wastewaters through an RO membrane. Membrane fouling caused by the secondary
      wastewater effluent led to a notable decrease in the permeation of N
      nitrosodimethylamine (NDMA) while a smaller but nevertheless discernible decrease
      in the permeation of N-nitrosomethylethylamine (NMEA), N-nitrosopyrrolidine
      (NPYR) and N-nitrosomorpholine (NMOR) was also observed. Fluorescence
      spectrometry analysis revealed that major foulants in the secondary wastewater
      effluent were humic and fulvic acid-like substances. Analysis using the size
      exclusion chromatography technique also identified polysaccharides and proteins
      as additional fouling substances. Thus, further examination was conducted using
      solutions containing model foulants (i.e., sodium alginate, bovine serum albumin,
      humic acid and two fulvic acids). Similar to the secondary wastewater effluent,
      membrane fouling with fulvic acid solutions resulted in a decrease in N
      nitrosamine permeation. In contrast, membrane fouling with the other model
      foulants resulted in a negligible impact on N-nitrosamine permeation. Overall,
      these results suggest that the impact of fouling on the permeation of N
      nitrosamines by RO is governed by specific small organic fractions (e.g. fulvic
      acid-like organics) in the secondary wastewater effluent.

PMID- 28431352
TI  - Degradation of sulfamethoxazole by UV, UV/H2O2 and UV/persulfate (PDS): Formation
      of oxidation products and effect of bicarbonate.
AB  - The frequent detection of sulfamethoxazole (SMX) in wastewater and surface waters
      gives rise of concerns about their ecotoxicological effects and potential risks
      to induce antibacterial resistant genes. UV/hydrogen peroxide (UV/H2O2) and
      UV/persulfate (UV/PDS) advanced oxidation processes have been demonstrated to be
      effective for the elimination of SMX, but there is still a need for a deeper
      understanding of product formations. In this study, we identified and compared
      the transformation products of SMX in UV, UV/H2O2 and UV/PDS processes. Because
      of the electrophilic nature of SO4-, the second-order rate constant for the
      reaction of sulfate radical (SO4-) with the anionic form of SMX was higher than
      that with the neutral form, while hydroxyl radical (OH) exhibited comparable
      reactivity to both forms. The direct photolysis of SMX predominately occurred
      through cleavage of the NS bond, rearrangement of the isoxazole ring, and
      hydroxylation mechanisms. Hydroxylation was the dominant pathway for the reaction
      of OH with SMX. SO4- favored attack on NH2 group of SMX to generate a nitro
      derivative and dimeric products. The presence of bicarbonate in UV/H2O2 inhibited
      the formation of hydroxylated products, but promoted the formation of the nitro
      derivative and the dimeric products. In UV/PDS, bicarbonate increased the
      formation of the nitro derivative and the dimeric products, but decreased the
      formation of the hydroxylated dimeric products. The different effect of
      bicarbonate on transformation products in UV/H2O2 vs. UV/PDS suggested that
      carbonate radical (CO3-) oxidized SMX through the electron transfer mechanism
      similar to SO4- but with less oxidation capacity. Additionally, SO4- and CO3-
      exhibited higher reactivity to the oxazole ring than the isoxazole ring of SMX.
      Ecotoxicity of transformation products was estimated by ECOSAR program based on
      the quantitative structure-activity relationship analysis as well as by
      experiments using Vibrio fischeri, and these results indicated that the oxidation
      of SO4- or CO3- with SMX generated more toxic products than those of OH.

PMID- 28431353
TI  - Discovery of potential anticancer multi-targeted ligustrazine based cyclohexanone
      and oxime analogs overcoming the cancer multidrug resistance.
AB  - The drug research and development nowadays is focusing on multi-target drugs. In
      the treatment of cancer, therapies using drugs inhibiting one numerous targets
      signify a novel viewpoint. In comparison with traditional therapy, multi-targeted
      drugs directly aim cell subpopulations which are involved in progression of
      tumor. The current study comprises the synthesis of 34 novel ligustrazine
      containing alpha, beta-unsaturated carbonyl-based compounds and oximes. The
      growth of 5 various cancer cell types was strongly inhibited by ligustrazine
      containing oximes as revealed by biological evaluation. A strong SAR was provided
      by the antiproliferative activity. The mechanistic effects of most active
      antiproliferative compounds on tubulin polymerization, EGFR TK kinases, KAF and
      BRAFV600E were investigated, followed by in vitro investigation of reversal of
      efflux-based resistance developed by cancer cells. EGFR was strongly inhibited by
      two oximes 7e and 8o. Out of all linkers including positive control, 1-isopropyl
      piperidin-4-one linker-bearing compounds showed best inhibition of FAK. The
      strongest inhibitory activity of BRAFV600E was showed by compound 5e with an IC50
      of 0.7 MUM. Analogs such as 5 and 7 (b,e,f) exhibited a dual role as anticancer
      as well as MDR reversal agents. For understanding the target protein integrations
      with new compounds, molecular docking studies were also carried out.

PMID- 28431354
TI  - First example of peptides targeting the dimer interface of Leishmania infantum
      trypanothione reductase with potent in vitro antileishmanial activity.
AB  - A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the
      linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH2 (Toro et al. ChemBioChem2013) has
      been designed and synthesized by introduction of the lactam between amino acid
      side chains that are separated by one helical turn (i, i+4). All of these
      compounds were tested in vitro as both dimerization and enzyme inhibitors of
      Leishmania infantum trypanothione reductase (Li-TryR). Three of the 13-mer cyclic
      peptide derivatives (3, 4 and 6) inhibited the oxidoreductase activity of Li-TryR
      in the low micromolar range and they also disrupted enzyme dimerization. Cyclic
      analogues 3 and 4 were more resistant to proteases than was the linear prototype.
      Furthermore, the most potent TryR inhibitors in the linear and cyclic series
      displayed potent in vitro activity against Leishmania infantum upon conjugation
      with cationic cell-penetrating peptides. To date, these conjugated peptides can
      be considered the first example of TryR dimerization inhibitors that are active
      in cell culture.

PMID- 28431355
TI  - Genome-wide identification and analysis of the Populus trichocarpa TIFY gene
      family.
AB  - The plant-specific TIFY proteins are widely present in land plants and play the
      important roles in the regulation of plant stress-responses. In this study, we
      carried out a bioinformatics analysis of TIFY genes in Populus trichocarpa by
      determining the phylogenetic relationship, chromosomal location and gene
      structure and expression profiles analysis under stresses. The 24 TIFY genes were
      identified and classified into four subfamilies (ZML, JAZ, PPD and TIFY). The 24
      TIFY genes were irregularly located on 13 of the 19 chromosomes; ten gene pairs
      were involved in large-scale interchromosomal segmental duplication events; we
      identified 17 collinear TIFY gene pairs in the Populus trichocarpa genome.
      Numerous abiotic stress cis-elements were widely found in the promoter regions.
      Analysis of the Ka/Ks ratios indicated that the paralogs of the PtTIFY family
      principally underwent purifying selection. Microarray data and qRT-PCR analysis
      revealed that 24 PtTIFY genes were differentially expressed in various tissues.
      Quantitative real-time RT-PCR analysis of TIFY genes expression in response to
      salt, JA hormones and low-temperature stress revealed their stress-responses
      profiles. The results of this study provided valuable information for further
      exploration of the TIFY gene family in Populus trichocarpa.

PMID- 28431356
TI  - Heavy metals pollution levels and children health risk assessment of Yerevan
      kindergartens soils.
AB  - Children, the most vulnerable urban population group, are exceptionally sensitive
      to polluted environments, particularly urban soils, which can lead to adverse
      health effects upon exposure. In this study, the total concentrations of Ag, As,
      Ba, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Ti, V, and Zn were determined in 111
      topsoil samples collected from kindergartens in Yerevan. The objectives of this
      study were to evaluate heavy metal pollution levels of kindergarten's soils in
      Yerevan, compare with national legal and international requirements on heavy
      metal contents in kindergarten soil, and assess related child health risk.
      Multivariate geostatistical analyses suggested that the concentrations of Ag, As,
      Ba, Cd, Cu, Hg, Mo, Pb, and Zn observed in the kindergarten's topsoil may have
      originated from anthropogenic sources, while Co, Cr, Fe, Mn, Ni, Ti, and V mostly
      come from natural sources. According to the Summary pollution index (Zc), 102
      kindergartens belong to the low pollution level, 7 to the moderate and only 2 to
      the high level of pollution. Summary concentration index (SCI) showed that 109
      kindergartens were in the allowable level, while 2 featured in the low level of
      pollution. The health risk assessment showed that in all kindergartens except for
      seven, non-carcinogenic risk for children was detected (HI>1), while carcinogenic
      risk from arsenic belongs to the very low (allowable) level. Cr and multi-element
      carcinogenic risk (RI) exceeded the safety level (1.0E- 06) in all kindergartens
      and showed that the potential of developing cancer, albeit small, does exist.
      Therefore, city's kindergartens require necessary remedial actions to eliminate
      or reduce soil pollution and heavy metal-induced health risks.

PMID- 28431357
TI  - Soil organic carbon and nitrogen pools drive soil C-CO2 emissions from selected
      soils in Maritime Antarctica.
AB  - The ongoing trend of increasing air temperatures will potentially affect soil
      organic matter (SOM) turnover and soil C-CO2 emissions in terrestrial ecosystems
      of Maritime Antarctica. The effects of SOM quality on this process remain little
      explored. We evaluated (i) the quantity and quality of soil organic matter and
      (ii) the potential of C release through CO2 emissions in lab conditions in
      different soil types from Maritime Antarctica. Soil samples (0-10 and 10-20cm)
      were collected in Keller Peninsula and the vicinity of Arctowski station, to
      determine the quantity and quality of organic matter and the potential to emit
      CO2 under different temperature scenarios (2, 5, 8 and 11 degrees C) in lab. Soil
      organic matter mineralization is low, especially in soils with low organic C and
      N contents. Recalcitrant C form is predominant, especially in the passive pool,
      which is correlated with humic substances. Ornithogenic soils had greater C and N
      contents (reaching to 43.15gkg-1 and 5.22gkg-1 for total organic carbon and
      nitrogen, respectively). C and N were more present in the humic acid fraction.
      Lowest C mineralization was recorded from shallow soils on basaltic/andesites. C
      mineralization rates at 2 degrees C were significant lower than at higher
      temperatures. Ornithogenic soils presented the lowest values of C-CO2 mineralized
      by g of C. On the other hand, shallow soils on basaltic/andesites were the most
      sensitive sites to emit C-CO2 by g of C. With permafrost degradation, soils on
      basaltic/andesites and sulfates are expected to release more C-CO2 than
      ornithogenic soils. With greater clay contents, more protection was afforded to
      soil organic matter, with lower microbial activity and mineralization. The trend
      of soil temperature increases will favor C-CO2 emissions, especially in the
      reduced pool of C stored and protected on permafrost, or in occasional Histosols.

PMID- 28431358
TI  - Molecular ecological perspective of methanogenic archaeal community in rice
      agroecosystem.
AB  - Methane leads to global warming owing to its warming potential higher than carbon
      dioxide (CO2). Rice fields represent the major source of methane (CH4) emission
      as the recent estimates range from 34 to 112 Tg CH4 per year. Biogenic methane is
      produced by anaerobic methanogenic archaea. Advances in high-throughput
      sequencing technologies and isolation methodologies enabled investigators to
      decipher methanogens to be unexpectedly diverse in phylogeny and ecology.
      Exploring the link between biogeochemical methane cycling and methanogen
      community dynamics can, therefore, provide a more effective mechanistic
      understanding of CH4 emission from rice fields. In this review, we summarize the
      current knowledge on the diversity and activity of methanogens, factors
      controlling their ecology, possible interactions between rice plants and
      methanogens, and their potential involvement in the source relationship of
      greenhouse gas emissions from rice fields.

PMID- 28431359
TI  - Reconstruction of microbial community structures as evidences for soil redox
      coupled reductive dechlorination of PCP in a mangrove soil.
AB  - The aim was to investigate the influence of pentachlorophenol (PCP) on the soil
      microbial communities and the coupled mechanism between PCP reductive
      dechlorination and soil redox under anaerobic condition. Accordingly, a slurry
      incubation experiment was carried out in which bacterial and archaeal communities
      were detected by MiSeq amplicon sequencing. The original microbial community
      balance was gradually disrupted and new microbial structure was reconstructed
      subsequently through self-regulation and acclimation during PCP transformation,
      coupling with the changes of soil biogeochemical redox dynamics. The phylum
      Bacteroidetes predominated during the earlier PCP dechlorination period and then
      was progressively replaced by Proteobacteria and Firmicutes groups when PCP was
      mostly transformed into 2,3,4,5-TeCP and 3,4,5-TCP. Heatmap and hierarchical
      cluster analysis revealed the Clostridium-like, Geobacter-like and
      Dehalococcoides-like organisms enriched concurrently during PCP reductive
      dechlorination processes. The relative abundance changes of the redox-active
      microorganisms, together with their relevance to the corresponding biogeochemical
      redox processes, showed that PCP dechlorination, Fe(III) and SO42- reduction, as
      well as methanogenesis were coupled terminal electron accepting processes. The
      combined analysis of the microbial function, the affinity for substrates (H2 and
      acetate) and the sensitivity for PCP toxicity by microorganisms might explain why
      electron transport chain has changed in soil biogeochemical redox process. Our
      study offers a comprehensive description of the impact of PCP on the soil
      microbial community structures, which could be very useful for understanding the
      regulation of soil nutrient and energy transfer during biogeochemical cycling
      processes in soils with significant inputs of exogenous pollutants.

PMID- 28431360
TI  - Contrasting dual (C, Cl) isotope fractionation offers potential to distinguish
      reductive chloroethene transformation from breakdown by permanganate.
AB  - cis-1,2-Dichloroethene (cis-DCE) and trichloroethene (TCE) are persistent, toxic
      and mobile pollutants in groundwater systems. They are both conducive to
      reductive dehalogenation and to oxidation by permanganate. In this study, the
      potential of dual element (C, Cl) compound specific isotope analyses (CSIA) for
      distinguishing between chemical oxidation and anaerobic reductive dechlorination
      of cis-DCE and TCE was investigated. Well-controlled cis-DCE degradation batch
      tests gave similar carbon isotope enrichment factors epsilonC (0/00), but starkly
      contrasting dual element isotope slopes Deltadelta13C/Deltadelta37Cl for
      permanganate oxidation (epsilonC=-260/00+/-60/00, Deltadelta13C/Deltadelta37Cl~
      125+/-47) compared to reductive dechlorination (epsilonC=-180/00+/-40/00,
      Deltadelta13C/Deltadelta37Cl~4.5+/-3.4). The difference can be tracked down to
      distinctly different chlorine isotope fractionation: an inverse isotope effect
      during chemical oxidation (epsilonCl=+0.20/00+/-0.10/00) compared to a large
      normal isotope effect in reductive dechlorination (epsilonCl=-3.30/00+/-0.90/00)
      (p?0.05). A similar trend was observed for TCE. The dual isotope approach was
      evaluated in the field before and up to 443days after a pilot scale permanganate
      injection in the subsurface. Our study indicates, for the first time, the
      potential of the dual element isotope approach for distinguishing cis-DCE (and
      TCE) concentration drops caused by dilution, oxidation by permanganate and
      reductive dechlorination both at laboratory and field scale.

PMID- 28431361
TI  - Uncertainty quantification and validation of 3D lattice scaffolds for computer
      aided biomedical applications.
AB  - A methodology is proposed for uncertainty quantification and validation to
      accurately predict the mechanical response of lattice structures used in the
      design of scaffolds. Effective structural properties of the scaffolds are
      characterized using a developed multi-level stochastic upscaling process that
      propagates the quantified uncertainties at strut level to the lattice structure
      level. To obtain realistic simulation models for the stochastic upscaling process
      and minimize the experimental cost, high-resolution finite element models of
      individual struts were reconstructed from the micro-CT scan images of lattice
      structures which are fabricated by selective laser melting. The upscaling method
      facilitates the process of determining homogenized strut properties to reduce the
      computational cost of the detailed simulation model for the scaffold. Bayesian
      Information Criterion is utilized to quantify the uncertainties with parametric
      distributions based on the statistical data obtained from the reconstructed strut
      models. A systematic validation approach that can minimize the experimental cost
      is also developed to assess the predictive capability of the stochastic upscaling
      method used at the strut level and lattice structure level. In comparison with
      physical compression test results, the proposed methodology of linking the
      uncertainty quantification with the multi-level stochastic upscaling method
      enabled an accurate prediction of the elastic behavior of the lattice structure
      with minimal experimental cost by accounting for the uncertainties induced by the
      additive manufacturing process.

PMID- 28431362
TI  - RNA aptamer-based electrochemical aptasensor for C-reactive protein detection
      using functionalized silica microspheres as immunoprobes.
AB  - C-reactive protein (CRP) is a widely accepted biomarker of cardiovascular disease
      and inflammation. In this study, a RNA aptamer-based electrochemical sandwich
      type aptasensor for CRP detection was described using the functionalized silica
      microspheres as immunoprobes. Silica microspheres (Si MSs), which have good
      monodispersity and uniform shape, were firstly synthesized. The silica
      microspheres functionlized with gold nanoparticles (Au NPs) provided large
      surface area for immobilizing signal molecules (Zinc ions, Zn2+) and antibodies
      (Ab). RNA aptamers, which were specific recognized to CRP, were assembled on the
      surface of Au NPs modified electrode via gold-sulfur affinity. In the presence of
      CRP, a sandwich structure of aptamer-CRP-immunoprobe was formed. Square wave
      voltammetry (SWV) was employed to record the sensing signal, and a clearly
      reductive peak corresponding to Zn2+ at about -1.16V (vs. SCE) was obtained.
      Under optimal conditions, the aptasensor showed wide linear range (0.005ngmL-1 to
      125ngmL-1) and low detection limit (0.0017ngmL-1 at a signal-to-noise ratio of
      3). Some possible interfering substance was also investigated, and the results
      obtained showed that the aptasensor possessed good selectivity. When the
      aptasensor was applied to real serum samples analysis, the satisfied results were
      obtained, indicating that the aptasensor possessed potential real application
      ability.

PMID- 28431363
TI  - Nanomaterial-based electrochemical sensors for arsenic - A review.
AB  - The existence of arsenic in the environment poses severe global health threats.
      Considering its toxicity, the sensing of arsenic is extremely important. Due to
      the complexity of environmental and biological samples, many of the available
      detection methods for arsenic have serious limitations on selectivity and
      sensitivity. To improve sensitivity and selectivity and to circumvent
      interferences, different electrode systems have been developed based on surface
      modification with nanomaterials including carbonaceous nanomaterials, metallic
      nanoparticles (MNPs), metal nanotubes (MNTs), and even enzymes. Despite the
      progress made in electrochemical sensing of arsenic, some issues still need to be
      addressed to realize cost effective, portable, and flow-injection type sensor
      systems. The present review provides an in-depth evaluation of the nanoparticle
      modified electrode (NME) based methods for the electrochemical sensing of
      arsenic. NME based sensing systems are projected to become an important option
      for monitoring hazardous pollutants in both environmental and biological media.

PMID- 28431364
TI  - The humanistic and economic burden of Dravet syndrome on caregivers and families:
      Implications for future research.
AB  - We reviewed the current literature with respect to the humanistic and financial
      burdens of Dravet Syndrome (DS) on the caregivers of children with DS, in order
      to (1) identify key unanswered questions or gaps in knowledge that need to be
      addressed and then, based on these knowledge gaps, (2) propose a research agenda
      for the scientific community to address in the coming decade. The findings
      support the conclusion that caring for a child with DS is associated with
      significant humanistic burden and direct costs. However, due in part to the
      paucity of studies, as well as the lack of measures of specific burden domains,
      there remains much that is not known regarding the burden of caregiving for
      children with DS. To address the significant knowledge gaps in this area,
      research is needed that will: (1) identify the specific domains of caregivers'
      lives that are impacted by caring for a child with DS; (2) identify or, if
      needed, develop measures of caregiving impact in this area; (3) identify the
      factors that influence DS caregiving burden; (4) develop and evaluate the
      efficacy of treatments for reducing the negative impact of DS and its
      comorbidities on DS caregivers; (5) quantify the direct medical costs associated
      with DS and DS comorbidities and identify the factors that influence these costs;
      and (6) quantify and fully explore the indirect costs of DS. Research that
      addresses these goals will provide the empirical foundation needed for improving
      the quality of life of children with DS and their families.

PMID- 28431365
TI  - Attitudes towards people with epilepsy in Moscow.
AB  - PURPOSE: To assess the knowledge and attitudes in Moscow towards people with
      epilepsy (PWE). METHODS: Data were collected from 1167 adults, permanent
      residents of Moscow, who were interviewed. A 10-item questionnaire was used
      addressing three major domains: familiarity with epilepsy (2 questions),
      understanding of epilepsy (5 questions), and attitude towards the PWE (3
      questions). Results were standardized to the Moscow population. RESULTS: The
      study population was generally well informed about epilepsy. About 80% "has
      heard" of epilepsy; however, personal acquaintance with PWE was reported by less
      than half of the study participants. The level of understanding of the disease
      and its etiology was quite low. About 60% of the survey participants believed
      that epilepsy was a type of mental retardation. One-third (34%) of respondents
      were afraid to stay in the proximity of PWE. Only 38% of the survey participants
      considered epilepsy to be curable; men significantly less frequently than women.
      Overall, the level of understanding of epilepsy was proportional to the level of
      education of respondents. Negative attitudes towards PWE were demonstrated in a
      significant part of the population. Almost half of the respondents would object
      to their child playing or studying with a child who has epilepsy and more than
      half (57%) were against the marriage of their daughter or son to a person with
      epilepsy. Two-fifths of the respondents ranked epilepsy as the "least preferred"
      of the six chronic diseases for a colleague. CONCLUSION: This is the first study
      on awareness and attitudes to PWE in the adult population of Moscow. The study
      demonstrated that the general public is familiar with epilepsy, but has a rather
      low level of understanding of essential aspects of the disease. There is an
      overall high level of negative attitudes towards PWE in Russia, creating a need
      for targeted interventions. These results reinforced the importance of public
      education in reducing the stigma of epilepsy.

PMID- 28431366
TI  - Efficacy and safety of a video-EEG protocol for genetic generalized epilepsies.
AB  - INTRODUCTION: Video-EEG has been used to characterize genetic generalized
      epilepsies (GGE). For best performance, sleep recording, photic stimulation,
      hyperventilation, and neuropsychological protocols are added to the monitoring.
      However, risks and benefits of these video-EEG protocols are not well
      established. The aim of this study was to analyze the efficacy and safety of a
      video-EEG neuropsychological protocol (VNPP) tailored for GGE and compare its
      value with that of routine EEG (R-EEG). METHODS: We reviewed the VNPP and R-EEG
      of patients with GGE. We considered confirmation of the clinical suspicion of a
      GGE syndrome and characterization of reflex traits as benefits; and falls,
      injuries, psychiatric and behavioral changes, generalized tonic-clonic (GTC)
      seizures, and status epilepticus (SE) as the main risks of the VNPP. RESULTS: The
      VNPPs of 113 patients were analyzed. The most common epileptic syndrome was
      juvenile myoclonic epilepsy (85.8%). The protocol confirmed a GGE syndrome in 97
      patients and 62 had seizures. Sleep recording had a provocative effect in 51.2%
      of patients. The second task that showed highest efficacy was praxis (39.3%)
      followed by hyperventilation (31.3%). Among the risks, 1.8% had GTC seizures and
      another 1.8%, SE. Eighteen percent of patients had persistently normal R-EEG,
      72.2% of them had discharges during VNPP. Generalized tonic-clonic seizures,
      myoclonic status epilepticus, and repeated seizures were the main risks of VNPP
      present in 6 (5.31%) patients while there were no complications during R-EEG.
      CONCLUSIONS: The VNPP in GGE is a useful tool in diagnosis and characterization
      of reflex traits, and is a safe procedure. Its use might preclude multiple R-EEG
      exams.

PMID- 28431367
TI  - Clinical characterization of the pre-ictal state in the pediatric population: A
      caretaker's perspective.
AB  - The unpredictability of seizures causes distress to patients with epilepsy and
      their caretakers. To date, no studies have explored seizure prediction
      specifically in the pediatric population. If the period of time preceding a
      seizure can be reliably identified, either by child or caretaker, there may be a
      role for pre-emptive interventions. The aim of this study was to investigate
      caretaker seizure prediction. A questionnaire was distributed to caretakers of
      patients with epilepsy. The patients were 0-21years old and experienced >=1
      seizure within the past year. We excluded patients with non-epileptic seizures or
      daily seizures. One hundred and fifty of 240 questionnaires met criteria. Of
      these, 32 (21.6%) caretakers indicated a positive report of seizure prediction.
      Age of seizure onset was earlier in the positive predictive group (3.3+/
      3.3years) than in the non-predictor group (5.3+/-4.8years) (p=0.01). The most
      common pre-ictal symptoms reported were being tired, hazy look, and sleepiness. A
      total of 76.6% of caretakers reported at least one seizure precipitant. The
      prevalence of positive caretaker seizure prediction in this study is similar to
      that of seizure self-prediction in adult studies. These findings will be used to
      design prospective online or electronic diary studies to further investigate the
      caretaker's, as well as children's, perspectives on seizure prediction. We
      anticipate that this investigation may lead to novel treatments during times of
      high seizure risk.

PMID- 28431368
TI  - Correlates of perceived stigma for people living with epilepsy: A meta-analysis.
AB  - OBJECTIVE: Epilepsy, one of the most common, serious chronic neurological
      diseases, is accompanied by different levels of perceived stigma that affects
      people in almost all age groups. This stigma can negatively impact the physical
      and mental health of people living with epilepsy (PLWE). Good knowledge of
      perceived stigma for PLWE is important. In this study, we conducted a meta
      analysis to identify the correlates of perceived stigma for PLWE. METHODS:
      Studies on factors associated with perceived stigma for PLWE, including
      sociodemographic, psychosocial, and disease-related variables, were searched in
      PubMed, PsychINFO, EMBASE, and Web of Science. RESULTS: Nineteen variables (k>1)
      were included in the meta-analysis. For sociodemographic characteristics,
      findings revealed that the significant weighted mean correlation (R) for
      "residence" and "poor financial status" were 0.177 and 0.286, respectively. For
      disease-related characteristics, all variables of significance, including
      "seizure severity," "seizure frequency," "number of medicines," and "adverse
      event" (R ranging from 0.190 to 0.362), were positively correlated with perceived
      stigma. For psychosocial characteristics, "depression" and "anxiety" with R
      values of 0.414 and 0.369 were significantly associated with perceived stigma. In
      addition, "social support," "quality of life (QOLIE-31,89)," "knowledge," and
      "attitude," with R values ranging from -0.444 to -0.200 indicating negative
      correlation with perceived stigma. CONCLUSION: The current meta-analysis
      evaluated the correlates of perceived stigma for PLWE. Results can serve as a
      basis for policymakers and healthcare professionals for formulating health
      promotion and prevention strategies.

PMID- 28431369
TI  - The temporal paradox of Hebbian learning and homeostatic plasticity.
AB  - Hebbian plasticity, a synaptic mechanism which detects and amplifies co-activity
      between neurons, is considered a key ingredient underlying learning and memory in
      the brain. However, Hebbian plasticity alone is unstable, leading to runaway
      neuronal activity, and therefore requires stabilization by additional
      compensatory processes. Traditionally, a diversity of homeostatic plasticity
      phenomena found in neural circuits is thought to play this role. However, recent
      modelling work suggests that the slow evolution of homeostatic plasticity, as
      observed in experiments, is insufficient to prevent instabilities originating
      from Hebbian plasticity. To remedy this situation, we suggest that homeostatic
      plasticity is complemented by additional rapid compensatory processes, which
      rapidly stabilize neuronal activity on short timescales.

PMID- 28431370
TI  - Hydrodynamic influence on reservoir sustainability in semi-arid climate: A
      physicochemical and environmental isotopic study.
AB  - Water scarcity and increasing water demand require the development of water
      management plans such as establishing artificial lakes and dams. Plans to meet
      water needs are faced by uprising challenges to improve water quality and to
      ensure the sustainability of hydro-projects. Environmental isotopes coupled to
      water physicochemical characteristics were investigated over a biennial cycle to
      assess both geomorphological and environmental impacts on the water quality of a
      reservoir situated in an intensively used agricultural watershed under a
      Mediterranean semi-arid climate. The particularity of the semi-arid climate and
      the diverse topography generate a continental and orographic rain effect on the
      isotopic composition of precipitation and the water recharged sources. The
      studied reservoir responds quickly to land-use activities and climatic changes as
      reflected by temporal and spatial variations of water chemistry and isotopic
      composition. Increasing changes in precipitation rate and dry periods
      significantly modified the water isotopic composition in the reservoir. During
      the first year, hydrogen (deltaD) and oxygen (delta18O) isotopes are depleted by
      6 and 20/00 between dry and wet season, respectively. While a shift of -20/00 for
      deltaD and -10/00 for delta18O was detected during the second annual cycle.
      Environmental isotopic compositions demonstrate for the first time the occurrence
      of groundwater inflow to the central (Cz) and dam (Dz) zones of the Qaraaoun
      reservoir. The Cz and Dz can be considered as open water bodies subjected to
      dilution by groundwater inflow, which induces vertical mixing and reverse
      isotopic stratification of the water column. In the contrary, the river mouth
      zone acts as a closed system without groundwater intrusion, where heavy water
      accumulates and may act as a sink for contaminants during dry season. Groundwater
      influx acts as a dilution factor that renews the hypolimnion, and minimizes the
      perturbations induced by both internal biogeochemical reactions and external
      hydrological variations. Attention should be devoted to the hydrogeological
      location of planned reservoirs, which should take into account the vicinity of
      shallow water table to insure good water quality and water sustainability.

PMID- 28431371
TI  - Past, present and future land use changes and their impact on water balance.
AB  - Landuse change influences the water balance of a region affecting the available
      water along with the change in the evapotranspiration (ET). The major objectives
      of this study are to assess the landuse change and its impact on the water
      balance of the study area, which is a part of the Narmada river basin in Madhya
      Pradesh, India. Landuse changes of 1990, 2000 and 2011 have been analyzed and the
      Markov Chain model has been used to predict decadal change of 2020, 2030, 2040
      and 2050 landuse. The influence of the past, present and future landuse change on
      water balance has been analyzed with the SWAT (Soil and Water Analysis Tool)
      model in the study area. The effect of changes are shown in 12 different sub
      watersheds of the area, reflecting an increased water yield (runoff, including
      ground-water outflow) and surface runoff but decreased ET, which is due to change
      in the curve number (CN) values (79.85 in 1990 to 84.63 in 2050). Increased CN
      value in different sub-watersheds of the region has been observed due to a
      reduction in the vegetation areas, and increase in the agricultural land and
      settlements. This has caused an increased runoff and decreased ET. The water
      yield has increased by 6.98% from 1990 to 2011 (1.92 CN increase) and by 17.5% as
      projected in the 2050 (4.78 CN increase). The actual ET decreases by 3.37% from
      1990 to 2011 and by 8.40% in 2050. Simulation with the SWAT using landuse change
      showed reduction in ET and increased runoff in different sub-watersheds, which
      needs to be considered in terms of management.

PMID- 28431372
TI  - Down-flow fixed-structured bed reactor: An innovative reactor configuration
      applied to acid mine drainage treatment and metal recovery.
AB  - A down-flow fixed-structured bed reactor (DFSBR) was operated for 277 days
      treating a mixture of synthetic substrates simulating an iron-rich acid mine
      drainage (AMD) and the soluble fraction of a sugarcane vinasse. The synthetic
      sugarcane vinasse was used as electron donor for biological sulfate-reduction,
      resulting in influent chemical oxygen demand (COD) close to 4000 mg L-1 and
      volumetric organic loading rate of 4.8 g L-1d-1. The influent sulfate
      concentration was kept close to 2000 mg L-1 (volumetric sulfate loading rate of
      2.5 g L-1d-1) while a gradual increase of iron concentration (2-400 mg L-1) was
      applied. COD removal efficiencies were higher than 93% and the sulfate removal
      efficiencies were close to 100%. With the highest iron concentration (400 mg L-1)
      applied, the DFSBR achieved 95% of iron removal efficiency. The precipitate
      collected at the reactor bottom showed increasing concentrations of fixed
      suspended solids (FSS), as well as an increasing proportion of iron, indicating
      the possibility of metal recovery from the system. The association between
      sulfidogenic and methanogenic processes also enables energy recovery from the
      methane-rich biogas produced.

PMID- 28431373
TI  - Development and validation of sustainability criteria of administrative green
      schools in Iran.
AB  - Environmental responsibility in school has led to the emergence of a variety of
      criteria to administer green schools' contributions to sustainability.
      Sustainability criteria of administrative green schools need validity,
      reliability and norms. The aim of the current study was to develop and validate
      assessment criteria for green schools in Iran based on the role of academia. A
      national survey was conducted to obtain data on sustainability criteria
      initiatives for green schools and the Iranian profile was defined. An initial
      pool of 71 items was generated and after its first edition, 63 items were
      selected to comprise the sustainability criteria. Engineering-architectural and
      behavioral aspects of this sustainability criteria were evaluated through a
      sample of 1218 graduate students with environmental degrees from Iran's
      universities. Exploratory factor analysis using principal components and promax
      rotation method showed that these 9 criteria have simple structures and are
      consistent with the theoretical framework. The reliability coefficients of
      subscales ranged between 0.62 (participation) and 0.84 (building location and
      position). The study's survey of correlation coefficients between items and
      subscales illustrated that those coefficients varied between 0.24 and 0.68.

PMID- 28431374
TI  - Atmospheric fallout radionuclides in peatland from Southern Poland.
AB  - Two peat profiles were collected in a peat bog located in Southern Poland and
      their geochronology were determined using 210Pb, 238,239+240Pu and 137Cs
      radiometric techniques. The 210Pb chronologies were established using the
      constant rate of supply model (CRS) and are in good agreement with the Pu
      isotopes and 137Cs time markers. Maximum activities of Pu isotopes were found at
      a depth corresponding to the early 1960s, which is the period characterized by
      the maximum nuclear weapon tests. The results showed that the 210Pb method is the
      most accurate technique for the determination age and accumulation rate of a
      peat. The next part of this study calculated linear accumulation rates by
      analyzing 238,239+240Pu and 137Cs vertical distributions in the profiles.
      Activities of fallout isotopes were also measured in plants covering the
      peatland. The highest activities of 137Cs and 210Pb were found in Calluna
      vulgaris samples, and 239+240Pu were found only in two samples (C. vulgaris and
      leaves of Oxycoccus quadripelatus).

PMID- 28431375
TI  - Radioactivity in wastes generated from shale gas exploration and production -
      North-Eastern Poland.
AB  - In the present study, the K-40, U-238, Ra-226, Pb-210, Ra-228 and Th-228 activity
      concentrations were measured in 64 samples of wastes generated from shale gas
      exploration in North-Eastern Poland. The measured samples consist of drill
      cuttings, solid phase of waste drilling muds, fracking fluids, return fracking
      fluids and waste proppants. The measured activity concentrations in solid samples
      vary in a wide range from 116 to around 1100 Bq/kg for K-40, from 14 to 393 Bq/kg
      for U-238, from 15 to 415 Bq/kg for Ra-226, from 12 to 391 Bq/kg for Pb-210, from
      a few Bq/kg to 516 Bq/kg for Ra-228 and from a few Bq/kg to 515 Bq/kg for Th-228.
      Excluding the waste proppants, the measured activity concentrations in solid
      samples oscillate around their worldwide average values in soil. In the case of
      the waste proppants, the activity concentrations of radionuclides from uranium
      and thorium decay series are significantly elevated and equal to several hundreds
      of Bq/kg but it is connected with the mineralogical composition of proppants. The
      significant enhancement of Ra-226 and Ra-228 activity concentrations after
      fracking process was observed in the case of return fracking fluids, but the
      radium isotopes content in these fluids is comparable with that in waste waters
      from copper and coal mines in Poland.

PMID- 28431376
TI  - Trichobezoar presenting as a gastric outlet obstruction: A case report.
AB  - INTRODUCTION: Rapunzel syndrome is a rare intestinal condition that starts with
      the ingestion of a trichobezoar. The condition is predominately found in females
      and can be associated with trichotillomania, or the compulsive urge to pull one's
      own hair out. There are less than 40 cases described in the literature with the
      prevention of recurrence aimed at psychological treatment. PRESENTATION OF CASE:
      The patient is a 7 year-old girl with a history of trichotillomania with
      trichophagia as a young child who presented with abdominal pain, nausea, and
      vomiting, consistent with a gastric outlet obstruction. She had an exploratory
      laparotomy with gastrostomy performed revealing a 18cm by 18cm trichobezoar with
      extension into the small bowel. DISCUSSION: Bezoars, an already rare entity, can
      occasionally lead to gastric and small bowel obstructions. Small collections of
      ingested hair build up in the intestinal tract causing significant symptoms.
      These obstructions can sometimes be treated through minimally invasive techniques
      but, in our case described, it is unlikely to have been treated any other way due
      to the substantial size of the trichobezoar. CONCLUSION: Early consideration of
      Rapunzel syndrome is important in young females presenting with a gastric outlet
      obstruction.

PMID- 28431377
TI  - Metabolic regulation and the anti-obesity perspectives of human brown fat.
AB  - Activation of brown adipose tissue (BAT) in adult humans increase glucose and
      fatty acid clearance as well as resting metabolic rate, whereas a prolonged
      elevation of BAT activity improves insulin sensitivity. However, substantial
      reductions in body weight following BAT activation has not yet been shown in
      humans. This observation raise the possibility for feedback mechanisms in adult
      humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines,
      factors produced by and secreted from brown fat. Batokines also seems to be
      involved in BAT recruitment by stimulating proliferation and differentiation of
      brown fat progenitors. Increasing human BAT capacity could thus include inducing
      brown fat biogenesis as well as identifying novel batokines. Another attractive
      approach would be to induce a brown fat phenotype, the so-called brite or beige
      fat, within the white fat depots. In adult humans, white fat tissue
      transformation into beige has been observed in patients with pheochromocytoma, a
      norepinephrine-producing tumor. Interestingly, human beige fat is predominantly
      induced in regions that were BAT during early childhood, possibly reflecting that
      a presence of human beige progenitors is depot specific and originating from BAT.
      In conclusion, to utilize the anti-obesity potential of human BAT focus should be
      directed towards identifying novel regulators of brown and beige fat progenitor
      cells, as well as feedback mechanisms of BAT activation. This would allow for
      identification of novel anti-obesity targets.

PMID- 28431378
TI  - Development of novel alternative biodiesel fuels for reducing PM emissions and PM
      related genotoxicity.
AB  - This paper intend to investigate the effects of biodiesel fuel blends comprising
      of waste-cooking oil and butanol-diesel (B10W10-B10W40) under steady-state
      conditions. Both particulate organic carbon (OC) and PM including PM2.5 and PM10
      significantly decreased with the increasing percentage of biodiesel fuel blends.
      The fuel blend of B10W40 also demonstrated the most effective function in
      reducing the emissions of PM10 and PM2.5 in the volume by 59.4% and 57.7%,
      respectively. Moreover, the emissions of nitrogen oxides decreased with the
      blending of B10W10-B10W40 (13.9-28.5%), while the brake specific fuel consumption
      was substantially increased (5.69-13.4%). The overall biological toxicity of PM10
      generated from the fuel tested in this study was determined according to Single
      Cell Gel Electrophoresis assay in human alveolar basal epithelial A549 cells and
      micronucleus assay in CHO-K1 cells. In addition, the volume of more than 20%
      waste-cooking oil (B10W20 and B10W40) significantly reduced diesel-induced
      genotoxicity in lung cells and micronucleus formation in CHO-K1 cells.
      Collectively, these results indicated that biodiesel fuel blends with the butanol
      could be a potential alternative fuels for diesel engines because of its
      substantial property with a significant reduction of the PM-related genotoxicity
      and the emissions of PM, particulate OC, and NOX.

PMID- 28431379
TI  - The effects of maternal and children phthalate exposure on the neurocognitive
      function of 6-year-old children.
AB  - The primary purpose of this study was to investigate the effects of phthalate
      exposure on the intelligence and attentional performance of 6-year old children
      when adjusting each other as covariates. We also investigated the differential
      effects of phthalate exposure on the intelligence and attention according to
      exposure period (maternal or children). Urine concentrations of mono-(2-ethyl-5
      hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and
      mono-n-butyl phthalate (MBP) were analyzed. Multivariable linear regression
      models were used to investigate the relationship between exposure to various
      phthalates with IQ scores and continuous performance test (CPT) variables. There
      were robust associations between child MEHHP and MEOHP levels with full scale IQ
      (FSIQ) even after adjusting for demographic variables and CPT scores (MEHHP 
      9.27, 95% CI: -17.25, -1.29; MEOHP -9.83, 95% CI: -17.44, -2.21). Child MEHHP and
      MEHOP levels negatively affected omission errors (MEHHP -20.36, 95% CI: -34.17, 
      6.55; MEOHP -18.93, 95% CI: -32.58, -5.28) and the response time variability
      (MEHHP -21.07, 95% CI: -39.04, -3.10; MEOHP -20.41, 95% CI -38.14, -2.69) of the
      CPT after adjusting for demographic variables and IQ. Maternal phthalate exposure
      had no effects on IQ or CPT variables. These results suggest that children
      phthalate exposure, but not maternal exposure, has an adverse effect on IQ and
      attentional performance, and these associations were found to be independent of
      each other.

PMID- 28431380
TI  - Recent aspects of uranium toxicology in medical geology.
AB  - Uranium (U) is a chemo-toxic, radiotoxic and even a carcinogenic element. Due to
      its radioactivity, the effects of U on humans health have been extensively
      investigated. Prolonged U exposure may cause kidney disease and cancer. The
      geological distribution of U radionuclides is still a great concern for human
      health. Uranium in groundwater, frequently used as drinking water, and general
      environmental pollution with U raise concerns about the potential public health
      problem in several areas of Asia. The particular paleo-geological hallmark of
      India and other Southern Asiatic regions enhances the risk of U pollution in
      rural and urban communities. This paper highlights different health and
      environmental aspects of U as well as uptake and intake. It discusses levels of U
      in soil and water and the related health issues. Also described are different
      issues of U pollution, such as U and fertilizers, occupational exposure in
      miners, use and hazards of U in weapons (depleted U), U and plutonium as
      catalysts in the reaction between DNA and H2O2, and recycling of U from
      groundwater to surface soils in irrigation. For use in medical geology and U
      research, large databases and data warehouses are currently available in Europe
      and the United States.

PMID- 28431381
TI  - Zeaxanthin ameliorates high glucose-induced mesangial cell apoptosis through
      inhibiting oxidative stress via activating AKT signalling-pathway.
AB  - Oxidative stress is a critical factor in the pathophysiology of diabetic kidney
      disease. Previous study shows that hyperglycaemia aggravates renal injury through
      oxidative stress in diabetic model, and antioxidants have beneficial effect on
      diabetic kidney disease. However, the role of antioxidants in the progression of
      diabetic kidney disease is poorly understood. The aim of this study was to
      clarify whether zeaxanthin, an antioxidant, could ameliorate mesangial cell
      injury and if so, identify the related mechanism underlying this protective
      effect. To that end, superoxide dismutase (SOD) activity and methane dicarboxylic
      aldehyde (MDA) levels were measured by an assay kit, and mesangial cell apoptosis
      and ROS levels were assessed using flow cytometry analysis. Furthermore, The
      levels of a phosphorylated ser/thr protein kinase (p-AKT), phosphorylated
      glycogen synthase kinase-3 beta (p-GSK-3beta), Bcl-2 associated X protein (Bax)
      and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were detected
      by western blot. We found that zeaxanthin decreases MDA levels and increased SOD
      activity, as well as inhibits apoptosis and decreases ROS levels in mesangial
      cells in a high sugar environment. Furthermore, zeaxanthin increased p-AKT levels
      while decreased the levels of p-GSK-3beta, Bax and cleaved-caspase-3. In
      addition, LY294002 reversed the protective effect of zeaxanthin on mesangial
      cells. In conclusion, zeaxanthin ameliorated mesangial cell apoptosis may be
      involved in inhibiting oxidative stress through activating of the AKT signalling
      pathway.

PMID- 28431383
TI  - Protocolized hyperventilation enhances electroconvulsive therapy.
AB  - BACKGROUND: Hyperventilation is recommended in electroconvulsive therapy (ECT) to
      enhance seizures and to increase patients' safety. However, more evidence is
      needed regarding its effects and the optimum method of application. METHODS: This
      prospective study involving 21 subjects compared two procedures, protocolized
      hyperventilation (PHV) and hyperventilation as usual (HVau), applied to the same
      patient in two consecutive sessions. Transcutaneous partial pressure of carbon
      dioxide (TcPCO2) was measured throughout all sessions. Ventilation parameters,
      hemodynamic measures, seizure characteristics, and side effects were also
      explored. RESULTS: PHV resulted in lower TcPCO2 after hyperventilation (p=.008)
      and over the whole session (p=.035). The lowest TcPCO2 was achieved after
      voluntary hyperventilation. Changes in TcPCO2 from baseline showed differences
      between HVau and PHV at each session time-point (all p<.05). Between- and within
      subjects factors were statistically significant in a general linear model.
      Seizure duration was greater in PHV sessions (p=.028), without differences in
      other seizure quality parameters or adverse effects. Correlations were found
      between hypocapnia induction and seizure quality indexes. LIMITATIONS: Secondary
      outcomes could be underpowered. CONCLUSIONS: PHV produces hypocapnia before the
      stimulus, modifies patients' TcPCO2 values throughout the ECT session and
      lengthens seizure duration. Voluntary hyperventilation is the most important part
      of the PHV procedure with respect to achieving hypocapnia. A specific ventilation
      approach, CO2 quantification and monitoring may be advisable in ECT. PHV is easy
      to apply in daily clinical practice and does not imply added costs. Ventilation
      management has promising effects in terms of optimizing ECT technique.

PMID- 28431382
TI  - Childhood maltreatment preceding depressive disorder at age 18 years: A
      prospective Brazilian birth cohort study.
AB  - BACKGROUND: Childhood maltreatment is linked with increased risk for mental
      illness in adolescence and adulthood. However, little evidence is available on
      whether different forms of maltreatment have specific effects, and no prospective
      studies in low- or middle-income countries have addressed this issue. METHODS:
      Participants in a population-based, birth cohort study in Pelotas, Brazil
      (N=3715) self-reported exposure to maltreatment (emotional abuse, physical
      neglect, physical abuse, sexual abuse, domestic violence) in confidential
      questionnaires at age 15 years, and were assessed for major depression in
      interviews at age 18 years, using the MINI. Confounding variables concerning
      family characteristics were measured in interviews with mothers in the perinatal
      period and at age 11 years. RESULTS: Females exposed to emotional abuse (OR=2.7;
      95%CI=1.9, 3.8) and domestic violence (OR=1.9; 95%CI=1.2, 2.9) were at increased
      risk for depression after adjustment for confounders and other types of
      maltreatment. Females exposed to two or more forms of maltreatment were at
      particularly high risk for depression (OR=4.1; 95%Cl=2.8, 6.1) compared with
      females not exposed to maltreatment. In adjusted analyses, maltreatment was not
      associated with depression for males. LIMITATIONS: Detailed information about
      maltreatment such as timing and frequency was not available, and 1534 individuals
      were not included in the analyses, who had poorer and less educated mothers.
      CONCLUSIONS: Emotional abuse and domestic violence are strong risk factors for
      major depression for females. Early intervention to prevent maltreatment and its
      consequences is critical, especially for girls exposed to poly-maltreatment.

PMID- 28431384
TI  - Sediment and salinity effects on the bioaccumulation of sulfamethoxazole in
      zebrafish (Danio rerio).
AB  - The dynamic distribution of a widely used antibiotic sulfamethoxazole between
      water, sediment and aquatic organisms (zebrafish) was studied in microcosms.
      Sulfamethoxazole concentrations in water were gradually reduced, while in
      sediment and zebrafish gradually increased, suggesting active adsorption and
      bioaccumulation processes occurring. The presence of sediment particles and their
      interactions with water reduced the bioaccumulation of sulfamethoxazole in
      zebrafish by 13-28%. The sediment of smaller particle size with more organic
      carbon content and higher surface area, adsorbed sulfamethoxazole more
      extensively and decreased its bioaccumulation most significantly. The effect
      became more severe with increasing salinity in water due to the salting out of
      sulfamethoxazole, resulting in 24-33% reduction in bioaccumulation. At
      equilibrium, the distribution of sulfamethoxazole in different phases was
      quantified, with most sulfamethoxazole being associated with water (97.3%),
      followed by sedimentary phase (2.7%) and finally zebrafish (0.05%). The findings
      provided important data for further research into antibiotics fate and bio-uptake
      in aquatic organisms, and subsequent ecotoxicity.

PMID- 28431385
TI  - A method for evaluating the pharmaceutical deconjugation potential in river water
      environments.
AB  - A new enzymatic assay method that uses deconjugation enzymes was developed to
      evaluate the presence and extent of conjugated pharmaceuticals in the form of
      glucuronide conjugates or sulphate conjugates in river environments. First,
      acetaminophen glucuronide (Ace Glu) and acetaminophen sulphate (Ace Sul) were
      used as model conjugated pharmaceuticals to determine the appropriate combination
      of deconjugation enzymes and reaction conditions, including temperature, duration
      and pH. Next, we applied the defined method to 19 pharmaceuticals grouped into
      nine therapeutic classes that were chosen based on previously detected levels and
      frequencies in sewage and river water. The enzymatic decomposition profile varied
      widely depending upon the enzyme preparations available. The effect of the water
      reaction temperature was small between 5 and 40  degrees C, and the reaction
      proceeded in for both glucuronide conjugates and sulphate conjugates at an
      approximately neutral pH (corresponding to usual river water conditions) within 1
      h. Application of the method to environmental samples showed that some
      pharmaceuticals were present in both glucuronide conjugate and sulphate
      conjugated forms, although glucuronide conjugates were the primary forms in the
      river water environment. Water treatment systems at sewage treatment plants were
      found to be effective for the removal of these conjugated compounds. The present
      results should be valuable in the environmental risk assessment of conjugated
      pharmaceuticals and in keeping river environments clean. To the best of our
      knowledge, this is the first report that enables the evaluation of the
      pharmaceutical deconjugation potential in a river environment.

PMID- 28431386
TI  - Tebuconazole alters morphological, behavioral and neurochemical parameters in
      larvae and adult zebrafish (Danio rerio).
AB  - In this study, we evaluated the effects of tebuconazole on morphology and
      exploratory larvae behavior and adult locomotion. Furthermore, we analyzed the
      effects of this fungicide on AChE activity and gene expression in zebrafish
      larvae and in the adult zebrafish brain. Tebuconazole (4 mg/L) increased the
      ocular distance in larvae and reduced the distance travelled, absolute turn
      angle, line crossing and time outside area in exposed larvae. Moreover, adult
      zebrafish that were exposed to this fungicide (4 and 6 mg/L) showed a decrease in
      distance travelled and mean speed when compared to the control group. However,
      tebuconazole did not alter the number of line crossings or time spent in the
      upper zone. Tebuconazole inhibited AChE activity at concentrations of 4 mg/L for
      larvae and 4 and 6 mg/L in the adult zebrafish brain. However, this fungicide did
      not alter AChE gene expression in the adult zebrafish brain but increased AChE
      mRNA transcript levels in larvae. These findings demonstrated that tebuconazole
      could modulate the cholinergic system by altering AChE activity and that this
      change may be associated with the reduced locomotion of these animals.

PMID- 28431387
TI  - Cypermethrin toxication leads to histopathological lesions and induces
      inflammation and apoptosis in common carp (Cyprinus carpio L.).
AB  - Cypermethrin (Cyp), a known neurotoxic pesticide, is widely used in agricultural
      applications. In the present study, the aim was to determine the
      histopathological effects of Cyp toxication and evaluate the activation of
      inducible nitric oxide synthetase (iNOS) and 8-hydroxy-2-deoxyguanosine (8-OHdG)
      using an immunofluorescence assay. Thereafter, we identified the expressions of
      caspase 3, capsase 8, iNOS, and metallothionein 1 (MT1) genes in common carp
      using quantitative reverse transcription polymerase chain reaction (qRT-PCR).
      High and low doses of Cyp were administered to experimental groups for 24, 48,
      72, and 96 h. As a result, necrotic neurons in different stages and desquamation
      of ependymal cells due to necrosis were detected in the brain. Histopathological
      changes, including hyperplasia of lamellar cells, telangiectasia of lamellae and
      thickening due to cellular infiltration in gills, hemorrhage, diffuse hydropic
      degeneration, and focal necrosis in the liver were observed in the experimental
      groups. Immunopositive reactions of 8-OHdG were clearly observed in the nuclei
      and cytoplasm of neurons, and positive reactions for iNOS were detected in the
      cytoplasm of neurons and in the glial cells of the experimental groups.
      Furthermore, we found that caspase 3, capsase 8, iNOS, and MT1 genes were up
      regulated in the brain when exposed to both high and low doses of Cyp. In
      conclusion, our findings revealed that Cyp toxication harms the organs of common
      carp, particularly the brain, and also gives rise to inflammation, DNA damage,
      and apoptosis. Therefore, the use of Cyp should be restricted to protect the
      health of aquatic animals.

PMID- 28431388
TI  - Retention and transport of graphene oxide in water-saturated limestone media.
AB  - In this work, column experiments were conducted to investigate the transport
      characteristics of graphene oxide (GO) nanoparticles in limestone media under
      various electrolytes, solution pH, and humic acid (HA) concentration conditions.
      In the limestone media, GO exhibited relatively low mobility with the mass
      recovery rate lower than 65.2%, even when solution ionic strength was low. The
      presence of HA enhanced its mobility. In addition, the presence of S2-, a
      divalent anion, also promoted GO transport in limestone media compared to Cl-
      under similar ionic strength conditions through neutralizing more positive charge
      and thus diminishing the cation bridging. Solution pH showed slight effect on the
      transport of GO in limestone with the mass recovery range from 40.3% to 51.7%.
      Over all, decreases in solution pH, HA concentration and increases in solution
      ionic strength reduced the mobility of GO in the limestone media under the tested
      conditions. These results indicated both environmental conditions and media
      characteristics played important roles in controlling GO fate and transport in
      porous media. The one-site kinetic deposition model was applied to describe the
      interactions between the GO and limestone media and model simulations fitted the
      observed experimental data very well. As limestone is an important component of
      aquiferous media in subsurface, findings from this study elucidated the key
      factors and processes controlling the fate of GO particles in limestone media,
      which can inform the prediction and assessment of the risks of GO in groundwater
      environment.

PMID- 28431389
TI  - Prediction of size-fractionated airborne particle-bound metals using MLR, BP-ANN
      and SVM analyses.
AB  - Size-fractionated heavy metal concentrations were observed in airborne
      particulate matter (PM) samples collected from 2014 to 2015 (spanning all four
      seasons) from suburban (Xianlin) and industrial (Pukou) areas in Nanjing, a
      megacity of southeast China. Rapid prediction models of size-fractionated metals
      were established based on multiple linear regression (MLR), back propagation
      artificial neural network (BP-ANN) and support vector machine (SVM) by using
      meteorological factors and PM concentrations as input parameters. About 38% and
      77% of PM2.5 concentrations in Xianlin and Pukou, respectively, were beyond the
      Chinese National Ambient Air Quality Standard limit of 75 MUg/m3. Nearly all
      elements had higher concentrations in industrial areas, and in winter among the
      four seasons. Anthropogenic elements such as Pb, Zn, Cd and Cu showed larger
      percentages in the fine fraction (o<=2.5 MUm), whereas the crustal elements
      including Al, Ba, Fe, Ni, Sr and Ti showed larger percentages in the coarse
      fraction (o > 2.5 MUm). SVM showed a higher training correlation coefficient (R),
      and lower mean absolute error (MAE) as well as lower root mean square error
      (RMSE), than MLR and BP-ANN for most metals. All the three methods showed better
      prediction results for Ni, Al, V, Cd and As, whereas relatively poor for Cr and
      Fe. The daily airborne metal concentrations in 2015 were then predicted by the
      fully trained SVM models and the results showed the heaviest pollution of
      airborne heavy metals occurred in December and January, whereas the lightest
      pollution occurred in June and July.

PMID- 28431390
TI  - Sulfonamides photoassisted oxidation treatments catalyzed by ilmenite.
AB  - This work assesses the feasibility of several advanced oxidation processes (CWPO
      Catalytic Wet Peroxide Oxidation), Photocatalysis and their combination (CWPO
      Photoassisted process) for sulfonamide antibiotic degradation. Raw ilmenite was
      used as catalyst in both processes, because of the presence of iron and titanium
      in its structure. Despite both treatments allowed reaching a total starting
      antibiotic depletion working at pH0 = 3 and T0 = 30  degrees C within 30 min
      reaction time, significant differences were observed in terms of mineralization.
      Thus, whereas photocatalytic process just reduced 35% of initial TOC after 120
      min, a 85% of mineralization was reached in the presence of H2O2 (CWPO
      Photoassisted process) which was related to the oxidation pathway. Only a 35% of
      mineralization was reached in case of CWPO. In this sense, the degradation route
      under CWPO-Photoassisted process displayed a mechanism based on the hydroxylation
      that led to lower molecular weight intermediates. On the contrary, under
      photocatalysis conditions, the appearance of higher molecular weight
      intermediates due to organic radical recombination indicates the prevailing of a
      condensation mechanism.

PMID- 28431391
TI  - Serum levels of lead, mercury and cadmium in relation to coronary artery disease
      in the elderly: A cross-sectional study.
AB  - BACKGROUND: There is a continuing attempt to identify novel factors that can
      predict the risk of cardiovascular disease beyond the established coronary risk
      factors. It has been suggested that serum levels of lead, mercury and cadmium are
      associated with the risk of coronary artery disease (CAD). In the present study,
      we aimed to evaluate serum concentrations of lead (s-Pb), mercury (s-Hg) and
      cadmium (s-Cd) in patients with CAD in comparison with those of healthy
      individuals. The correlation between serum levels of these heavy metals and lipid
      profile parameters was also investigated. METHODS: In this case-control study, we
      included 65 patients (35 females) aged 50-70 years with angiographically
      documented CAD and 65 healthy controls (43 female) matched for sex, age and place
      of residence. Serum concentrations of heavy metals were determined using graphite
      furnace atomic absorption (GFAA). Serum lipids were measured using routine
      enzymatic methods. RESULTS: It was observed that the mean concentration of s-Pb
      (12.54 +/- 8.41 vs. 5.89 +/- 4.44 MUg/L, p < 0.05) and s-Cd (0.938 +/- 0.72 vs.
      0.448 +/- 0.30, p < 0.05; CI: 95%) and s-Hg (10.14 +/- 5.06 vs. 6.11 +/- 5.66, p
      < 0.05) were significantly higher in CAD patients compared with control subjects.
      The same result was also obtained after adjustment for cardiovascular risk
      factors including age, dyslipidemia, diabetes mellitus and hypertension (p <
      0.05). The mean concentration of total cholesterol (TC), high-density lipoprotein
      cholesterol (HDL-C) and TC:HDL-C ratio were significantly higher in CAD patients
      (p < 0.05). There was no significant association between serum metal
      concentrations with TC, HDL-C and TC:HDL-C ratio (p > 0.05). CONCLUSIONS: The
      present results showed that serum levels of heavy metals are associated with the
      presence of CAD. Long-term exposure to trace levels of Pb, Cd and Hg may play a
      role in the development of coronary atherosclerotic plaques.

PMID- 28431392
TI  - Characterization of Aurora A and Its Impact on the Effect of Cisplatin-Based
      Chemotherapy in Patients with Non-Small Cell Lung Cancer.
AB  - BACKGROUND AND OBJECTIVE: Aurora A, as a member of serine/threonine kinase family
      and a common characteristic of epithelial cancers, plays a critical role in cell
      mitosis. However, the clinical significance of Aurora A in non-small cell lung
      cancer (NSCLC) remains undetermined. METHODS: The expression of Aurora A in NSCLC
      and paired normal adjacent lung tissues was determined by immunohistochemistry,
      Western blot, and reverse transcriptase polymerase chain reaction. Receiver
      operating characteristic (ROC) curve analysis was employed to determine a cutoff
      score for Aurora A expression in a training set (n=135). For validation, the ROC
      derived cutoff score was subjected to analysis of the association of Aurora A
      expression with patient outcome and clinicopathological characteristics in a
      testing set (n=128) and overall patients (n=263). The correlation of Aurora A
      with cisplatin resistance and epithelial-mesenchymal transition (EMT) was
      examined in vitro in NSCLC cells by overexpression or knockdown of Aurora A.
      RESULTS: Aurora A expression was significantly upregulated in tumor tissues
      compared with paired normal tissues (P<.01). The expression of Aurora A was
      closely associated with clinical stage, lymph node metastasis, and recurrence and
      was an independent prognostic parameter in multivariate analysis. High level of
      Aurora A expression predicted poorer overall survival and disease-free survival
      in NSCLC patients treated with cisplatin-based adjuvant chemotherapy. In vitro
      data showed that overexpression or knockdown of Aurora A resulted in increased or
      decreased cellular resistance to cisplatin. Furthermore, inhibition of Aurora A
      reversed the EMT process. CONCLUSIONS: Aurora A was identified as an inferior
      prognostic and cisplatin-resistant biomarker in NSCLC patients, which provided
      potential evidences for therapeutic target and reversing drug resistance.

PMID- 28431393
TI  - Loss of Tpm4.1 leads to disruption of cell-cell adhesions and invasive behavior
      in breast epithelial cells via increased Rac1 signaling.
AB  - Here we report the identification and characterization of a novel high molecular
      weight isoform of tropomyosin, Tpm4.1, expressed from the human TPM4 gene. Tpm4.1
      expression is down-regulated in a subset of breast cancer cells compared with
      untransformed MCF10A breast epithelial cells and in highly metastatic breast
      cancer cell lines derived from poorly metastatic MDA-MD-231 cells. In addition,
      patients with invasive ductal breast carcinoma show decreased TPM4 expression
      compared with patients with ductal breast carcinoma in situ, and low TPM4
      expression is associated with poor prognosis. Loss of Tpm4.1 using siRNA in
      MCF10A cells increases cell migration in wound-healing and Boyden chamber assays
      and invasion out of spheroids as well as disruption of cell-cell adhesions. Down
      regulation of Tpm4.1 in MDA-MB-231 cells leads to disruption of actin
      organization and increased cell invasion and dissemination from spheroids into
      collagen gels. The down-regulation of Tpm4.1 induces Rac1-mediated alteration of
      myosin IIB localization, and pharmacologic inhibition of Rac1 or down-regulation
      of myosin IIB using siRNA inhibits the invasive phenotypes in MCF10A cells. Thus
      Tpm4.1 plays an important role in blocking invasive behaviors through Rac1-myosin
      IIB signaling and our findings suggest that decreased expression of Tpm4.1 might
      play a crucial role during tumor progression.

PMID- 28431394
TI  - Effect of Salmonella enterica serovar Typhimurium VNP20009 and VNP20009 with
      restored chemotaxis on 4T1 mouse mammary carcinoma progression.
AB  - A variety of bacterial strains have been evaluated as bio-therapeutic and
      immunomodulatory agents to treat cancer. One such strain, Salmonella enterica
      serovar Typhimurium VNP20009, which is attenuated by a purine auxotrophic
      mutation and modified lipid A, is characterized in previous models as a safely
      administered, tumor colonizing agent. However, earlier work tended to use less
      aggressive cancer cell lines and immunocompromised animal models. Here, we
      investigated the safety and efficacy of VNP20009 in a highly malignant murine
      model of human breast cancer. Additionally, as VNP20009 has recently been found
      to have a defective chemotaxis system, we tested whether restoring chemotaxis
      would improve anti-cancer properties in this model system. Exposure to VNP20009
      had no significant effect on primary mammary tumor size or pulmonary metastasis,
      and the tumor colonizing process appeared chemotaxis independent. Moreover, tumor
      bearing mice exposed to Salmonella exhibited increased morbidity that was
      associated with significant liver disease. Our results suggest that VNP20009 may
      not be safe or efficacious when used in aggressive, metastatic breast cancer
      models utilizing immunocompetent animals.

PMID- 28431395
TI  - Correlation of genomic alterations assessed by next-generation sequencing (NGS)
      of tumor tissue DNA and circulating tumor DNA (ctDNA) in metastatic renal cell
      carcinoma (mRCC): potential clinical implications.
AB  - INTRODUCTION: Tumor tissue and circulating tumor DNA (ctDNA) next-generation
      sequencing (NGS) testing are frequently performed to detect genomic alterations
      (GAs) to help guide treatment in metastatic renal cell carcinoma (mRCC),
      especially after progression on standard systemic therapy. Our objective was to
      assess if GAs detected by ctDNA NGS are different from those detected by tumor
      tissue NGS, specifically in patients with mRCC, and if these platforms are
      interchangeable or complimentary. RESULTS: When controlling for genes tested by
      both platforms, the median mutation rate for ctDNA was similar to tissue (median
      3.0 vs. 1.0, p = 0.14). However, the concordance rate between the two platforms
      was only 8.6%. When comparing GAs by molecular pathway, GAs in tumor tissue were
      more common for the DNA repair and epigenetic pathways. MATERIALS AND METHODS:
      Results of NGS testing from tumor tissue and ctDNA from 19 sequential mRCC
      patients were compared. GAs in each were statistically evaluated using the
      Wilcoxon signed-rank test. The Fischer's exact test was used to compare the
      incidence of mutations in selected molecular pathways. CONCLUSIONS: When
      controlling for genes tested by both platforms, similar number of GAs were
      detected by both tissue and ctDNA based NGS. However, there was discordance in
      the type of GAs detected suggesting that ctDNA NGS may be more reflective of
      dynamic tumor genomic heterogeneity. Hence, these two platforms may be considered
      complementary to each other, rather than interchangeable, for assessment of tumor
      GAs to guide selection of targeted clinical trial therapies.

PMID- 28431396
TI  - Skeletal muscle measures and physical function in older adults with cancer:
      sarcopenia or myopenia?
AB  - BACKGROUND: Skeletal muscle loss, commonly known as sarcopenia, is highly
      prevalent in older adults and linked with adverse outcomes in cancer, yet the
      definition and role of sarcopenia remains uncertain. The aim of this study was to
      examine the association of Computerized Tomography (CT) assessed skeletal muscle
      measures with physical function in older adults with cancer. RESULTS: CTs for 185
      patients were available. Median age 73 (IQR 68-76) and 56.5% female. After
      controlling for sex and BMI, we found no evidence that SMI was associated with
      physical function impairments. Both SMD and SMG were associated physical function
      impairments and higher values were associated with decreased limitations in
      instrumental activities of daily living (RR 0.84 [CI 0.73-0.96] and 0.94 [CI 0.89
      0.99], respectively), climbing stairs (RR 0.84 [CI 0.76-0.94] and 0.91 [CI 0.87
      0.96]), walking 1 block (RR 0.77 [CI 0.67-0.90] and 0.91 [CI 0.85-0.97]), and
      prolonged Timed Up and Go (RR 0.83 [CI 0.75-0.92] and 0.92 [CI 0.88-0.96]).
      MATERIALS AND METHODS: Using the Carolina Senior Registry, we identified patients
      with CT imaging performed within 60 days +/- of baseline geriatric assessment
      (GA). Skeletal muscle area and density (SMD) were analyzed from L3 lumbar
      segments. Muscle area and height (m2) were used to calculate skeletal muscle
      index (SMI). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD.
      CONCLUSIONS: Skeletal muscle mass as assessed from CT imaging was not associated
      with physical function impairments. Skeletal muscle radiodensity was more
      associated with physical function and may aid in identifying older adults at risk
      for functional impairments.

PMID- 28431400
TI  - Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal
      stem cell sheets to accelerate fracture healing.
AB  - Fracture nonunion and delayed union continue to pose challenges for orthopedic
      surgeons. In the present study, we combined HMGB1 gelatin sponges with MSC sheets
      to promote bone healing after surgical treatment of rat tibial fractures. The
      HMGB1 gelatin sponge scaffolds supported the expansion of mesenchymal stem cells
      (MSCs) and promoted the osteogenic differentiation of MSCs and MSC sheets.
      Lentiviral vectors were then used to overexpress HMGB1 in MSCs. The results
      indicated that HMGB1 promotes the osteogenic differentiation of MSCs through the
      STAT3 pathway. Both siRNA and a STAT3 inhibitor downregulated STAT3, further
      confirming that HMGB1 induces the osteogenic differentiation of MSCs partly via
      the STAT3 signal pathway. In a rat tibial osteotomy model, we demonstrated the
      ability of HMGB1 gelatin sponge scaffolds to increase bone formation. The
      addition of MSC sheets further enhanced fracture healing. These findings support
      the use of HMGB1-loaded gelatin sponge scaffolds combined with MSC sheets to
      enhance fracture healing after surgical intervention.

PMID- 28431397
TI  - Sensitization of tamoxifen-resistant breast cancer cells by Z-ligustilide through
      inhibiting autophagy and accumulating DNA damages.
AB  - Autophagy plays a pro-survival role in the tamoxifen-resistant breast cancer
      cells. Herein we found that autophagy was concomitantly induced in tamoxifen
      resistant MCF-7 (MCF-7TR5) cells through the dissociation of Bcl-2 from Beclin 1
      and subsequent enhancement of interaction among the ATG14-Beclin1-PI3KC3 complex.
      Moreover, higher level of DNA damage was observed in MCF-7TR5 cells with the
      decreased BRCA1 and RAD51 level and the increased Ku80 level. Interestingly,
      Nur77 was selectively degraded by autophagy, which causes the release of Ku80
      from the Nur77-Ku80 complex, resulting in the increase of the DNA binding of Ku80
      and DNA-PKcs. Meanwhile, Z-ligustilide, a phthalide compound from Radix Angelica
      sinensis, was shown to inhibit the autophagic flux by blocking the autophagosome
      lysosome fusion. Importantly, Z-ligustilide-mediated autophagy inhibition
      restored Nur77 expression in MCF-7TR5 cells. Furthermore, Z-ligustilide promoted
      the interaction of Nur77 with Ku80 and thereby abolished the association of DNA
      PKcs with DNA ends. Moreover, Z-ligustilide sensitized MCF-7TR5 cells in a
      caspase-independent cell death and enhanced the DNA damage caused by tamoxifen,
      which was found to be attenuated by shNur77. Together, these findings not only
      provide important insights into the formation of tamoxifen resistance in breast
      cancer cells, but also suggest Z-ligustilide may function as a novel autophagy
      inhibitor to overcome chemoresistance.

PMID- 28431403
TI  - Association of the VDAC3 gene polymorphism with sperm count in Han-Chinese
      population with idiopathic male infertility.
AB  - Voltage-dependent anion channel (VDAC) is a multifunctional channel protein
      across the outer mitochondrial membrane of somatic cells and participates in many
      physiological and pathophysiological processes. Up to now, only a few studies,
      including our previous studies, showed that VDAC exists in mammalian spermatozoa
      and is involved in spermatogenesis and sperm functions. There is no report about
      VDAC genetic variants in germinal tissues or cells. To investigate the possible
      association between VDAC genetic variants and human sperm quality, we performed
      semen analysis and variant Genotyping of VDAC3 subtype (rs7004637, rs16891278 and
      rs6773) of 523 Han-Chinese males with idiopathic infertility respectively by
      computer assisted semen analysis (CASA) and single nucleotide polymorphism (SNP)
      Genotyping assay. No significant association was found between rs7004637 and
      rs6773 genotypes and semen quality. However, the AG genotype of rs16891278 showed
      a significantly lower sperm concentration compared with the AA genotype (P =
      0.044). Our findings suggest that VDAC3 genetic variants may be associated with
      human sperm count.

PMID- 28431406
TI  - ERK expression and its correlation with STAT1 in esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: Esophageal squamous cell carcinoma is one of leading causes of cancer
      related deaths in Chaoshan region a high-risk region for esophageal cancer.
      Extracellular regulated protein kinases (ERK) usually play an important role in
      cell proliferation and differentiation. However, accumulating evidence has shown
      that the ERK was aberrantly expressed in cancers and correlated with STAT1
      depression. RESULTS: The activated ERK downregulates STAT1 expression in ESCC
      cell lines and U0126 increases expression of STAT1. Our immunohistochemistry
      result also confirms that the expression of ERK inversely correlated with that of
      STAT1 in ESCC tumors. In addition, a significantly higher expression of ERK/p-ERK
      was found in ESCC tissues in comparison with case-matched normal esophageal
      tissues (p < 0.05). Moreover, the immunohistochemical analysis demonstrated that
      ERK expression was paralleled with the differentiation and clinical stage. In 74
      patients with follow-up data, those with ERKlow tumors survived significantly
      longer than those with ERKhigh tumors (p = 0.04); patients with ERKlow/STAT1high
      tumors had the longest survival (p = 0.001). MATERIALS AND METHODS: To
      investigate whether ERK can mediated STAT1 expression in ESCC, we used the MEK
      plasmid and U0126, a MEK inhibitor, to treat the cell. To further confirm our in
      vitro study, we detected the ERK, p-ERK and STAT1 expression in 131 ESCC cases
      and 22 case-matched normal esophageal tissues adjacent to the tumors specimens.
      CONCLUSIONS: These findings provide pathological evidence that ERK/p-ERK is
      negatively correlated with STAT1 in ESCC. Our data suggests that inhibition of
      ERK and/or restoration of STAT1 expression maybe useful therapeutic strategies
      for ESCC.

PMID- 28431408
TI  - Effects of Exercise Modality During Additional "High-Intensity Interval Training"
      on Aerobic Fitness and Strength in Powerlifting and Strongman Athletes.
AB  - Androulakis-Korakakis, P, Langdown, L, Lewis, A, Fisher, JP, Gentil, P, Paoli, A,
      and Steele, J. Effects of exercise modality during additional "high-intensity
      interval training" on aerobic fitness and strength in powerlifting and strongman
      athletes. J Strength Cond Res 32(2): 450-457, 2018-Powerlifters and strongman
      athletes have a necessity for optimal levels of muscular strength while
      maintaining sufficient aerobic capacity to perform and recover between events.
      High-intensity interval training (HIIT) has been popularized for its efficacy in
      improving both aerobic fitness and strength but never assessed within the
      aforementioned population group. This study looked to compare the effect of
      exercise modality, e.g., a traditional aerobic mode (AM) and strength mode (SM),
      during HIIT on aerobic fitness and strength. Sixteen well resistance-trained male
      participants, currently competing in powerlifting and strongman events, completed
      8 weeks of approximately effort- and volume-matched HIIT in 2 groups: AM
      (cycling, n = 8) and SM (resistance training, n = 8). Aerobic fitness was
      measured as predicted V[Combining Dot Above]O2max using the YMCA 3 minutes step
      test and strength as predicted 1 repetition maximum from a 4-6RM test using a leg
      extension. Both groups showed significant improvements in both strength and
      aerobic fitness. There was a significant between-group difference for aerobic
      fitness improvements favoring the AM group (p <= 0.05). There was no between
      group difference for change in strength. Magnitude of change using within-group
      effect size for aerobic fitness and strength was considered large for each group
      (aerobic fitness, AM = 2.6, SM = 2.0; strength, AM = 1.9, SM = 1.9). In
      conclusion, our results support enhanced strength and aerobic fitness
      irrespective of exercise modality (e.g., traditional aerobic and resistance
      training). However, powerlifters and strongman athletes wishing to enhance their
      aerobic fitness should consider HIIT using an aerobic HIIT mode.

PMID- 28431409
TI  - Outcomes of Hemiarthroplasty and Total Hip Arthroplasty for Femoral Neck
      Fracture: A Medicare Cohort Study.
AB  - OBJECTIVES: For patients with femoral neck fractures, total hip arthroplasty
      (THA) demonstrates superior outcomes compared with hemiarthroplasty. However,
      hemiarthroplasty remains a common treatment for femoral neck fractures and the
      conversion rates are unknown. We compared the results of the 2 procedures using a
      Medicare database. METHODS: We assembled a cohort of 70,242 patients 65 to 90
      years of age with an ICD9 diagnosis and matching Current Procedure Terminology
      code for femoral neck fracture between 2008 and 2012. Patients were followed
      forward for 2 years minimum. Incidences of dislocation and mortality were
      measured. Reoperation for revision of THA or conversion of hemiarthroplasty to
      THA was assessed by Current Procedure Terminology code. Groups were compared
      through proportional hazard models controlling for age, race, sex, and
      comorbidity index. RESULTS: Hemiarthroplasty represented 95% of the patients
      treated using arthroplasty for femoral neck fracture. The proportional hazard of
      reoperation and dislocation were significantly lower for hemiarthroplasty than
      THA (P < 0.0001 for both). At 2 years, fewer than 2% of hemiarthroplasty patients
      underwent conversion to total hip replacement. Patients treated with THA were
      more likely to be alive for 2 years (adjusted hazard ratio = 1.67, 95% confidence
      interval: 1.59-1.92). CONCLUSION: Patients treated with hemiarthroplasty after
      femoral neck fractures had significantly lower proportional hazard of reoperation
      than those treated with THA. THA may be associated with lower mortality. LEVEL OF
      EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 28431410
TI  - Gravity Stress Radiographs and the Effect of Ankle Position on Deltoid Ligament
      Integrity and Medial Clear Space Measurements.
AB  - INTRODUCTION: External rotation and gravity stress radiographs have been
      described to distinguish stable supination-external rotation-II (SER-II) ankle
      fractures from unstable SER-IV fractures. It has been previously shown that both
      external rotation and gravity stress views are equivalent in their ability to
      diagnose deltoid ligament injury. It has also been shown that the position of the
      ankle influences the external rotation stress radiograph. However, no data of
      ankle position exist for gravity stress radiographs. METHODS: Eight fresh-frozen
      cadaveric ankles were dissected and destabilized sequentially according to the
      SER mechanism of ankle fractures, starting with the anterior inferior
      tibiofibular ligament, distal fibula osteotomy at the level of the syndesmosis,
      posterior inferior tibiofibular ligament, superficial deltoid ligament, and
      finally the deep deltoid ligament. Fluoroscopic radiographs were taken with
      gravity stress views in both neutral and plantarflexion. Measurements of both
      dorsal and the medial clear space were taken for each stage. The difference
      between the dorsal and medial clear space was measured. RESULTS: Positive
      predictive value (PPV) with a medial clear space cutoff of 5 mm was 80% in
      plantarflexion and 72.72% in neutral with a negative predictive value (NPV) of
      100% in both positions. Using a 6-mm cutoff, the PPV improved to 100% and NPV
      remained 100% for both neutral and plantarflexion. When the difference
      measurement is used, a 1.0-mm difference yielded a PPV of 72% and an NPV of 100%
      in both neutral and plantarflexion. With a 1.5-mm cutoff, the PPV and NPV were
      100% for both positions. CONCLUSIONS: The position of the ankle during gravity
      stress radiographs does not influence the clinical effectiveness of the images.
      Using larger references for stability, the PPV can be improved.

PMID- 28431411
TI  - Influence of Fracture Stability on Early Patient Mortality and Reoperation After
      Pertrochanteric and Intertrochanteric Hip Fractures: Erratum.

PMID- 28431412
TI  - Cutaneous Malignant Melanoma With Rhabdoid Morphology and Smooth Muscle
      Differentiation: A Challenging Histopathologic Diagnosis.
AB  - Divergent differentiation or metaplastic change is a rare feature exhibited
      occasionally in malignant melanoma (MM), which is characterized by the
      development of morphologically, immunochemically, and/or ultrastructurally
      nonmelanocytic cells within the tumor. Smooth muscle differentiation in MM is an
      exceedingly rare phenomenon reported only in a few cases in the literature. We
      report the case of a 69-year-old woman who presented with a pure dermal
      amelanotic MM with smooth muscle cell differentiation and an area of rhabdoid
      morphology, which made the accurate histopathologic diagnostic of MM challenging.

PMID- 28431413
TI  - Novel oral anticoagulants and trauma: The results of a prospective American
      Association for the Surgery of Trauma Multi-Institutional Trial.
AB  - BACKGROUND: The number of anticoagulated trauma patients is increasing. Trauma
      patients on warfarin have been found to have poor outcomes, particularly after
      intracranial hemorrhage (ICH). However, the effect of novel oral anticoagulants
      (NOAs) on trauma outcomes is unknown. We hypothesized that patients on NOAs would
      have higher rates of ICH, ICH progression, and death compared with patients on
      traditional anticoagulant and antiplatelet agents. METHODS: This was a
      prospective observational trial across 16 trauma centers. Inclusion criteria was
      any trauma patient admitted on aspirin, clopidogrel, warfarin, dabigatran,
      rivaroxaban, or apixaban. Demographic data, admission vital signs, mechanism of
      injury, injury severity scores, laboratory values, and interventions were
      collected. Outcomes included ICH, progression of ICH, and death. RESULTS: A total
      of 1,847 patients were enrolled between July 2013 and June 2015. Mean age was
      74.9 years (SD +/- 13.8), 46% were female, 77% were non-Hispanic white. At least
      one comorbidity was reported in 94% of patients. Blunt trauma accounted for 99%
      of patients, and the median Injury Severity Score was 9 (interquartile range, 4
      14). 50% of patients were on antiplatelet agents, 33% on warfarin, 10% on NOAs,
      and 7% on combination therapy or subcutaneous agents.Patients taking NOAs were
      not at higher risk for ICH on univariate (24% vs. 31%) or multivariate analysis
      (incidence rate ratio, 0.78; confidence interval 0.61-1.01, p = 0.05). Compared
      with all other agents, patients on aspirin (90%, 81 mg; 10%, 325 mg) had the
      highest rate (35%) and risk (incidence rate ratio, 1.27; confidence interval,
      1.13-1.43; p < 0.001) of ICH. Progression of ICH occurred in 17% of patients and
      was not different between medication groups. Study mortality was 7% and was not
      significantly different between groups on univariate or multivariate analysis.
      CONCLUSION: Patients on NOAs were not at higher risk for ICH, ICH progression, or
      death. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

PMID- 28431414
TI  - Intratracheal instillation of neutrophils rescues bacterial overgrowth initiated
      by trauma damage-associated molecular patterns.
AB  - BACKGROUND: Nosocomial pneumonias are common in trauma patients and so
      interventions to prevent and treat nosocomial pneumonia may improve outcomes. Our
      prior work strongly suggests that tissue injury predisposes to infections like
      nosocomial pneumonia because mitochondrial debris originating from injured cells
      contains damage-associated molecular patterns that can reduce neutrophil (PMN)
      migration into the airway and diminish PMN function in response to bacterial
      inoculation of the airway. This suggested that putting exogenous "normal" PMN
      into the airway might be beneficial. METHODS: Postinjury pneumonia (PNA) commonly
      arises in two groups, early, community-acquired PNA (CAP) and later hospital
      acquired PNA (HAP). Posttraumatic early-onset CAP and late-onset HAP were modeled
      in CD-1 mice using Staphylococcus aureus or Pseudomonas aeruginosa instilled
      intratracheal (i.t.) at clinically relevant times with or without extrapulmonary
      injuries mimicked by an intraperitoneal application of mitochondrial damage
      associated molecular patterns. We applied bone marrow-derived PMN (BM-PMN)
      intratracheally to assess their effect on bacterial clearance in the lung.
      RESULTS: BM-PMN instillation i.t. had no untoward clinical effects on recipient
      animals. In both the early/CAP and late/HAP models, clearance of the bacterial
      inoculum from the lung was suppressed by mitochondrial debris and restored to
      uninjured levels by i.t. instillation of exogenous BM-PMN. Furthermore, PMN
      instillation cleared the inoculum of P. aeruginosa that could not be cleared by
      uninjured mice. Instillation of PMN into the lung, even across strains (CD-1 vs.
      C57BL/6) had no injurious effect. CONCLUSION: These initial studies suggest PMN
      instillation (i.t.) is worthy of further study as a potential adjunctive therapy
      aimed at decreasing the morbidity of lung infections in trauma patients.
      Moreover, PMN instillation (i.t.) may represent a unique means of preventing or
      treating pneumonia after serious injury that is completely independent of the
      need for antibiotic use.

PMID- 28431415
TI  - Potential impact of Affordable Care Act-related insurance expansion on trauma
      care reimbursement.
AB  - BACKGROUND: Nearly one quarter of trauma patients are uninsured and hospitals
      recoup less than 20% of inpatient costs for their care. This study examines
      changes to hospital reimbursement for inpatient trauma care if the full coverage
      expansion provisions of the Affordable Care Act (ACA) were in effect. METHODS: We
      abstracted nonelderly adults (ages 18-64 years) admitted for trauma from the
      Nationwide Inpatient Sample during 2010-the last year before most major ACA
      coverage expansion policies. We calculated national and facility-level
      reimbursements and trauma-related contribution margins using Nationwide Inpatient
      Sample-supplied cost-to-charge ratios and published reimbursement rates for each
      payer type. Using US census data, we developed a probabilistic microsimulation
      model to determine the proportion of pre-ACA uninsured trauma patients that would
      be expected to gain private insurance, Medicaid, or remain uninsured after full
      implementation of the ACA. We then estimated the impact of these coverage changes
      on national and facility-level trauma reimbursement for this population. RESULTS:
      There were 145,849 patients (representing 737,852 patients nationwide) included.
      National inpatient trauma costs for patients aged 18 years to 64 years totaled US
      $14.8 billion (95% confidence interval [CI], 12.5,17.1). Preexpansion
      reimbursements totaled US $13.7 billion (95% CI, 10.8-14.7), yielding a national
      margin of -7.9% (95% CI, -10.6 to -5.1). Postexpansion projected reimbursements
      totaled US $15.0 billion (95% CI, 12.7-17.3), increasing the margin by 9.3
      absolute percentage points to +1.4% (95% CI, -0.3 to +3.2). Of the 263 eligible
      facilities, 90 (34.2%) had a positive trauma-related contribution margin in 2010,
      which increased to 171 (65.0%) using postexpansion projections. Those facilities
      with the highest proportion of uninsured and racial/ethnic minorities experienced
      the greatest gains. CONCLUSION: Health insurance coverage expansion for uninsured
      trauma patients has the potential to increase national reimbursement for
      inpatient trauma care by over one billion dollars and nearly double the
      proportion of hospitals with a positive margin for trauma care. These data
      suggest that insurance coverage expansion has the potential to improve trauma
      centers' financial viability and their ability to provide care for their
      communities. LEVEL OF EVIDENCE: Economic analysis, level II.

PMID- 28431416
TI  - Caring for critically injured children: An analysis of 56 pediatric damage
      control laparotomies.
AB  - BACKGROUND: Injury is the leading cause of death in children under 18 years.
      Damage control principles have been extensively studied in adults but remain
      relatively unstudied in children. Our primary study objective was to evaluate the
      use of damage control laparotomy (DCL) in critically injured children. METHODS:
      An American College of Surgeons-verified Level 1 trauma center review (1996-2013)
      of pediatric trauma laparotomies was undertaken. Exclusion criteria included: age
      older than 18 years, laparotomy for abdominal compartment syndrome or delayed
      longer than 2 hours after admission. Demographics, mechanism, resuscitation
      variables, injuries, need for DCL, and outcomes were evaluated. Independent t
      test, Mann-Whitney U test, Fisher's exact test, and single-factor analysis of
      variance assessed statistical significance. Study endpoints were hospital
      survival and DCL complications. RESULTS: Of 371 children who underwent trauma
      laparotomy, the median age (IQR; LQ-UQ) age was 16 (5; 11-17) years. Most (73%)
      were male injured by blunt mechanism (65%). Fifty-six (15%) children (Injury
      Severity Score [ISS], 33 (25; 17-42), pediatric trauma score 5 (6; 2-8),
      penetrating abdominal trauma index score [PATI] 29 (32; 12-44)) underwent DCL
      after major solid organ (63%), vascular (36%), thoracic (38%) and pelvic (36%)
      injury. DCL patients were older (16.5 (4; 14-18) vs. 16 (7; 10-17)) and were more
      severely injured (ISS, 33 [25; 17-42] vs. 16 [16; 9-25]), requiring greater
      intraoperative packed red blood cell transfusion (8 [13; 3.5-16.5] vs. 1 (0; [0
      1] units) than definitive laparotomy counterparts. Nonsurvivors arrived in severe
      physiologic compromise (base deficit, 17 [17; 8-25] vs. 7 [4; 4-8]), requiring
      more frequent preoperative blood product transfusion (67% vs. 10%) after
      comparable injury (ISS survivors, 36 [23; 18-41] vs. nonsurvivors 26 (7; 25-32),
      p = 0.8880). Fifty-five percent of DCL patients survived (length of stay, 26 [21;
      18-39] days) requiring 3 (2; 2-4) laparotomies during 4 (6; 2-8) days until
      closure (fascial, 90%; vicryl/split thickness skin grafting, 10%). DCL
      complications (surgical site infection, 18%; dehiscence, 2%; enterocutaneous
      fistula, 2%) were analyzed. When stratified by age (<15 years vs. 15-18 years)
      and period (1996-2006 vs. 2007-2013), no differences were found in injury
      severity or DCL outcomes (p > 0.05). After controlling for DCL, age, and gender,
      multivariate analysis indicated only ISS (odds ratio, 1.10 [95% confidence
      interval, 1.01 - 1.19], p = 0.0218) and arrival systolic blood pressure (odds
      ratio, 0.96 [95% confidence interval, 0.93-0.99], p = 0.0254) predicted mortality
      after severe injury. CONCLUSION: DCL is a proven, lifesaving surgical technique
      in adults. This report is the first to analyze the use of DCL in children with
      critical abdominal injuries. With similar survival and morbidity rates as
      critically injured adults, DCL merits careful consideration in children with
      critical abdominal injuries. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 28431417
TI  - The occurrence of single and multiple organ dysfunction in pediatric electrical
      versus other thermal burns.
AB  - BACKGROUND: Multiple organ failure (MOF) is a major contributor to morbidity and
      mortality in burned children. While various complications induced by electrical
      injuries have been described, the incidence and severity of single organ failure
      (SOF) and MOF associated with this type of injury are unknown. The study was
      undertaken to compare the incidence and severity of SOF and MOF as well as other
      complications between electrically and thermally burned children. PATIENTS AND
      METHODS: Between 2001 and 2016, 288 pediatric patients with electrical burns (EB;
      n = 96) or thermal burns (CTR; n = 192) were analyzed in this study. Demographic
      data; length of hospitalization; and number and type of operations, amputations,
      and complications were statistically analyzed. Incidence of SOF and MOF was
      assessed using the DENVER2 classification in an additive mixed model over time.
      Compound scores and organ-specific scores for lung, heart, kidney, and liver were
      analyzed. Serum cytokine expression profiles of both groups were also compared
      over time. Significance was accepted at p < 0.05. RESULTS: Both groups were
      comparable in age (CTR, 11 +/- 5 years, vs EB, 11 +/- 5 years), percent total
      body surface area burned (CTR, 33% +/- 25%, vs EB, 32 +/- 25%), and length of
      hospitalization (CTR, 18 +/- 26 days, vs EB, 18 +/- 21 days). The percentage of
      high-voltage injury in the EB group was 64%. The incidence of MOF was lower in
      the EB group (2 of 96 [2.1%]) than the CTR group (20 of 192 [10.4%]; p < 0.05).
      The incidence of single organ failure was comparable between groups. Incidence of
      pulmonary failure was comparable in both groups, but incidence of inhalation
      injury was significantly higher in the CTR group (p < 0.0001). Patients in the EB
      group had more amputations (p < 0.001), major amputations (p = 0.001), and
      combined major amputations (p < 0.01). Mortality was comparable between the
      groups. Serum cytokine expression profiles were also comparable between the
      groups. CONCLUSIONS: In pediatric patients, electrical injury is associated with
      a lower incidence of MOF than other thermal burns. Early and radical debridement
      of nonviable tissue is crucial to improve outcomes in the electrical burn patient
      population. LEVEL OF EVIDENCE: Retrospective chart review, level III.

PMID- 28431419
TI  - Creation and Validation of an Automated Algorithm to Determine Postoperative
      Ventilator Requirements After Cardiac Surgery.
AB  - BACKGROUND: In medical practice today, clinical data registries have become a
      powerful tool for measuring and driving quality improvement, especially among
      multicenter projects. Registries face the known problem of trying to create
      dependable and clear metrics from electronic medical records data, which are
      typically scattered and often based on unreliable data sources. The Society for
      Thoracic Surgery (STS) is one such example, and it supports manually collected
      data by trained clinical staff in an effort to obtain the highest-fidelity data
      possible. As a possible alternative, our team designed an algorithm to test the
      feasibility of producing computer-derived data for the case of postoperative
      mechanical ventilation hours. In this article, we study and compare the accuracy
      of algorithm-derived mechanical ventilation data with manual data extraction.
      METHODS: We created a novel algorithm that is able to calculate mechanical
      ventilation duration for any postoperative patient using raw data from our EPIC
      electronic medical record. Utilizing nursing documentation of airway devices,
      documentation of lines, drains, and airways, and respiratory therapist ventilator
      settings, the algorithm produced results that were then validated against the STS
      registry. This enabled us to compare our algorithm results with data collected by
      human chart review. Any discrepancies were then resolved with manual calculation
      by a research team member. RESULTS: The STS registry contained a total of 439
      University of California Los Angeles cardiac cases from April 1, 2013, to March
      31, 2014. After excluding 201 patients for not remaining intubated, tracheostomy
      use, or for having 2 surgeries on the same day, 238 cases met inclusion criteria.
      Comparing the postoperative ventilation durations between the 2 data sources
      resulted in 158 (66%) ventilation durations agreeing within 1 hour, indicating a
      probable correct value for both sources. Among the discrepant cases, the
      algorithm yielded results that were exclusively correct in 75 (93.8%) cases,
      whereas the STS results were exclusively correct once (1.3%). The remaining 4
      cases had inconclusive results after manual review because of a prolonged
      documentation gap between mechanical and spontaneous ventilation. In these cases,
      STS and algorithm results were different from one another but were both within
      the transition timespan. This yields an overall accuracy of 99.6% (95% confidence
      interval, 98.7%-100%) for the algorithm when compared with 68.5% (95% confidence
      interval, 62.6%-74.4%) for the STS data (P < .001). CONCLUSIONS: There is a
      significant appeal to having a computer algorithm capable of calculating metrics
      such as total ventilator times, especially because it is labor intensive and
      prone to human error. By incorporating 3 different sources into our algorithm and
      by using preprogrammed clinical judgment to overcome common errors with data
      entry, our results proved to be more comprehensive and more accurate, and they
      required a fraction of the computation time compared with manual review.

PMID- 28431420
TI  - Generative Retrieval Improves Learning and Retention of Cardiac Anatomy Using
      Transesophageal Echocardiography.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) is a valuable monitor for
      patients undergoing cardiac and noncardiac surgery as it allows for evaluation of
      cardiovascular compromise in the perioperative period. It is challenging for
      anesthesiology residents and medical students to learn to use and interpret TEE
      in the clinical environment. A critical component of learning to use and
      interpret TEE is a strong grasp of normal cardiovascular ultrasound anatomy.
      METHODS: Fifteen fourth-year medical students and 15 post-graduate year (PGY) 1
      and 2 anesthesiology residents without prior training in cardiac anesthesia or
      TEE viewed normal cardiovascular anatomy TEE video clips; participants were
      randomized to learning cardiac anatomy in generative retrieval (GR) and standard
      practice (SP) groups. GR participants were required to verbally identify each
      unlabeled cardiac anatomical structure within 10 seconds of the TEE video
      appearing on the screen. Then a correctly labeled TEE video clip was shown to the
      GR participant for 5 more seconds. SP participants viewed the same TEE video
      clips as GR but there was no requirement for SP participants to generate an
      answer; for the SP group, each TEE video image was labeled with the correctly
      identified anatomical structure for the 15 second period. All participants were
      tested for intermediate (1 week) and late (1 month) retention of normal TEE
      cardiovascular anatomy. Improvement of intermediate and late retention of TEE
      cardiovascular anatomy was evaluated using a linear mixed effects model with
      random intercepts and random slopes. RESULTS: There was no statistically
      significant difference in baseline score between GR (49% +/- 11) and SP (50% +/-
      12), with mean difference (95% CI) -1.1% (-9.5, 7.3%). At 1 week following the
      educational intervention, GR (90% +/- 5) performed significantly better than SP
      (82% +/- 11), with mean difference (95% CI) 8.1% (1.9, 14.2%); P = .012. This
      significant increase in scores persisted in the late posttest session at one
      month (GR: 83% +/- 12; SP: 72% +/- 12), with mean difference (95% CI) 10.2% (1.3
      to 19.1%); P = .026. Mixed effects analysis showed significant improvements in
      TEE cardiovascular anatomy over time, at 5.9% and 3.5% per week for GR and SP
      groups respectively (P = .0003), and GR improved marginally faster than SP (P =
      .065). CONCLUSIONS: Medical students and anesthesiology residents inexperienced
      in the use of TEE showed both improved learning and retention of basic
      cardiovascular ultrasound anatomy with the incorporation of GR into the
      educational experience.

PMID- 28431421
TI  - Sevoflurane Posttreatment Attenuates Lung Injury Induced by Oleic Acid in Dogs.
AB  - BACKGROUND: In animal models, both sevoflurane and propofol protect against acute
      lung injury (ALI), especially when administered prior to ALI onset. We
      hypothesized that when compared to propofol, sevoflurane administration after the
      onset of acute respiratory distress syndrome would mitigate oleic acid (OA)
      induced ALI in dogs. METHODS: Dogs were randomly assigned to receive intravenous
      OA to induce ALI (n = 7 for each OA group) or saline as an OA control (n = 6 for
      each control). Dogs were then mechanically ventilated for 6 hours during which
      propofol (5 mg/kg/h) or sevoflurane (1.0 minimum alveolar concentration) was
      administered for sedation. Study end points included PO2/FIO2 ratio, pulmonary
      arterial pressure, pulmonary edema, histology, and tumor nuclear factor-alpha.
      RESULTS: In OA-injured animals, oxygenation was worse at 1, 2, 3, and 4 hours
      after 6-hour mechanical ventilation in sevoflurane-sedated animals compared with
      propofol-sedated animals, with mean difference (95% confidence interval; propofol
      minus sevoflurane) of 75 (39-111), 87 (55-119), 66 (44-87), and 67 (27-107) mm Hg
      for the respective time points. However, sevoflurane reduced the elevated
      pulmonary arterial pressure and vascular resistance, attenuated pulmonary edema
      as evidenced by reduced extravascular lung water index, and decreased tumor
      nuclear factor-alpha and diffuse alveolar damage score compared with propofol in
      the OA-injured lungs. CONCLUSIONS: When compared with propofol, sevoflurane
      attenuates OA-induced lung damage. However, despite this effect on lung histology
      and inflammation, sevoflurane worsened oxygenation in OA-induced ALI, possibly
      via inhibition of hypoxic pulmonary vasoconstriction.

PMID- 28431422
TI  - How Long Is Too Long? The Prespiked Intravenous Debate.
AB  - BACKGROUND: As the number of operative cases increases, there is a greater
      emphasis on reducing inefficiency while maintaining patient safety. Recently, the
      issue of prespiking intravenous (IV) bags was raised. No study has assessed
      whether the risk of infection is related to the length of time a sterile (IV)
      fluid bag has been spiked. After completion of a pilot study revealed no
      microbial growth within 24 hours of an IV spike, a larger formal study was
      undertaken to determine whether there was an increased infection risk within 4
      hours of spiking an intravenous fluid bag. METHODS: Five IV administration sets
      were spiked and hung in busy perioperative areas once a week for a 5-week period.
      Five samples were drawn from each IV set. Approximately 10 mL was collected per
      sample. All samples were inoculated in 2 separate growth media. If any growth was
      noted, the sample was marked as positive. RESULTS: A total of 125 samples were
      collected over a period of 5 weeks, yielding 250 specimens. No samples were
      excluded from the study. No growth was identified in any of the specimens. The
      95% confidence interval was estimated to be 0, 0.063. DISCUSSION: There was no
      bacterial growth in prespiked normal saline IV bags in a perioperative
      environment. Thus, prespiking of normal saline IV bags in advance should pose no
      risk of infection to a patient if prepared within 4 hours.

PMID- 28431423
TI  - Blood Bupivacaine Concentrations After a Combined Single-Shot Sciatic Block and a
      Continuous Femoral Nerve Block in Pediatric Patients: A Prospective Observational
      Study.
AB  - We evaluated blood bupivacaine concentrations in children having a single-shot
      sciatic and continuous femoral blocks after anterior cruciate ligament repair.
      Dried blood spot samples were analyzed for bupivacaine levels at 0, 5, 15, 30,
      60, and 120 minutes and 4, 24, and 48 hours. The highest 99% upper confidence
      interval limit was 135 ng/mL at the 4-hour evaluation point. The 99% upper
      confidence interval was below potentially toxic levels (1500 ng/mL) across all
      sampling times. The risk of local anesthetic toxicity in pediatric patients
      receiving single-shot sciatic and continuous femoral nerve blocks is very low.

PMID- 28431424
TI  - Sleep-Disordered Breathing, Postoperative Delirium, and Cognitive Impairment.
AB  - Sleep-disordered breathing (SDB) is highly prevalent in the general population
      and has been associated with cognitive impairment in older individuals. Delirium
      is an acute decline in cognitive function and attention that often occurs after
      surgery, especially in older individuals. Several recent studies suggest an
      association between SDB and postoperative delirium. The aim of this systematic
      review is to examine the current literature on SDB, postoperative delirium, and
      cognitive impairment and to discuss the pathophysiology and perioperative
      considerations. A literature search was performed of Medline (1946-2016), Medline
      In-Process (June 2016), Embase (1947-2016), Cochrane Central Register of
      Controlled Trials (May 2016), and Cochrane Database of Systematic Reviews (2005
      to June 2016). Inclusion criteria for studies were (1) polysomnography confirmed
      SDB; (2) postoperative delirium or cognitive impairment confirmed by a validated
      diagnostic tool; and (3) publications in the English language. All study designs
      including randomized controlled trials and observational studies were included.
      The literature search identified 2 studies on SDB and postoperative delirium, 15
      studies on SDB and cognitive impairment, and 5 studies on the effect of
      continuous positive airway pressure on cognitive impairment and delirium in older
      individuals. SDB was associated with cognitive impairment, and this systematic
      review revealed that SDB may be a risk factor for postoperative delirium,
      especially in older individuals. Although the pathophysiology of SDB and
      postoperative delirium is unclear and effective treatments for SDB to reduce the
      incidence of delirium have not been studied extensively, preliminary evidence
      suggests that continuous positive airway pressure therapy may lower the risk of
      delirium. Health care professionals need to be aware that undiagnosed SDB may
      contribute to postoperative delirium. Preoperative screening for SDB and
      strategies to reduce the risk for postoperative delirium may be helpful in older
      individuals. Further studies are needed to clarify the relationship between SDB
      and postoperative delirium and elucidate the pathophysiology of postoperative
      delirium through SDB.

PMID- 28431425
TI  - The Association of Frailty With Outcomes and Resource Use After Emergency General
      Surgery: A Population-Based Cohort Study.
AB  - BACKGROUND: Older patients undergoing emergency general surgery (EGS) experience
      high rates of postoperative morbidity and mortality. Studies focused primarily on
      elective surgery indicate that frailty is an important predictor of adverse
      outcomes in older surgical patients. The population-level effect of frailty on
      EGS is poorly described. Therefore, our objective was to measure the association
      of preoperative frailty with outcomes in a population of older patients
      undergoing EGS. METHODS: We created a population-based cohort study using linked
      administrative data in Ontario, Canada, that included community-dwelling
      individuals aged >65 years having EGS. Our main exposure was preoperative
      frailty, as defined by the Johns Hopkins Adjusted Clinical Groups frailty
      defining diagnoses indicator. The Adjusted Clinical Groups frailty-defining
      diagnoses indicator is a binary variable that uses 12 clusters of frailty
      defining diagnoses. Our main outcome measures were 1-year all-cause mortality
      (primary), intensive care unit admission, length of stay, institutional
      discharge, and costs of care (secondary). RESULTS: Of 77,184 patients, 19,779
      (25.6%) were frail. Death within 1 year occurred in 6626 (33.5%) frail patients
      compared with 11,366 (19.8%) nonfrail patients. After adjustment for
      sociodemographic and surgical confounders, this resulted in a hazard ratio of
      1.29 (95% confidence interval [CI] 1.25-1.33). The risk of death for frail
      patients varied significantly across the postoperative period and was
      particularly high immediately after surgery (hazard ratio on postoperative day 1
      = 23.1, 95% CI 22.3-24.1). Frailty was adversely associated with all secondary
      outcomes, including a 5.82-fold increase in the adjusted odds of institutional
      discharge (95% CI 5.53-6.12). CONCLUSIONS: After EGS, frailty is associated with
      increased rates of mortality, institutional discharge, and resource use.
      Strategies that might improve perioperative outcomes in frail EGS patients need
      to be developed and tested.

PMID- 28431426
TI  - Anesthesiologists and Disaster Medicine: A Needs Assessment for Education and
      Training and Reported Willingness to Respond.
AB  - BACKGROUND: Anesthesiologists provide comprehensive health care across the
      emergency department, operating room, and intensive care unit. To date,
      anesthesiologists' perspectives regarding disaster medicine and public health
      preparedness have not been described. METHODS: Anesthesiologists' thoughts and
      attitudes were assessed via a Web-based survey at 3 major academic institutions.
      Frequencies, percentages, and odds ratios (ORs) were used to assess self-reported
      perceptions of knowledge and skills, as well as attitudes and beliefs regarding
      education and training, employee development, professional obligation, safety,
      psychological readiness, efficacy, personal preparedness, and willingness to
      respond (WTR). Three representative disaster scenarios (natural disaster [ND],
      radiological event [RE], and pandemic influenza [PI]) were investigated. Results
      are reported as percent or OR (95% confidence interval). RESULTS: Participants
      included 175 anesthesiology attendings (attendings) and 95 anesthesiology
      residents (residents) representing a 47% and 51% response rate, respectively. A
      minority of attendings indicated that their hospital provides adequate pre-event
      preparation and training (31% [23-38] ND, 14% [9-21] RE, and 40% [31-49] PI). Few
      residents felt that their residency program provided them with adequate
      preparation and training (22% [14-33] ND, 16% [8-27] RE, and 17% [9-29] PI).
      Greater than 85% of attendings (89% [84-94] ND, 88% [81-92] RE, and 87% [80-92]
      PI) and 70% of residents (81% [71-89] ND, 71% [58-81] RE, and 82% [70-90] PI)
      believe that their hospital or residency program, respectively, should provide
      them with preparation and training. Approximately one-half of attendings and
      residents are confident that they would be safe at work during response to a ND
      or PI (55% [47-64] and 58% [49-67] of attendings; 59% [48-70] and 48% [35-61] of
      residents, respectively), whereas approximately one-third responded the same
      regarding a RE (31% [24-40] of attendings and 28% [18-41] of residents). Fewer
      than 40% of attendings (34% [26-43]) and residents (38% [27-51]) designated who
      would take care of their family obligations in the event they were called into
      work during a disaster. Regardless of severity, 79% (71-85) of attendings and 73%
      (62-82) of residents indicated WTR to a ND, whereas 81% (73-87) of attendings and
      70% (58-81) of residents indicated WTR to PI. Fewer were willing to respond to a
      RE (63% [55-71] of attendings and 52% [39-64] of residents). In adjusted logistic
      regression analyses, those anesthesiologists who reported knowing one's role in
      response to a ND (OR, 15.8 [4.5-55.3]) or feeling psychologically prepared to
      respond to a ND (OR, 6.9 [2.5-19.0]) were found to be more willing to respond.
      Similar results were found for RE and PI constructs. Both attendings and
      residents were willing to respond in whatever capacity needed, not specifically
      to provide anesthesia. CONCLUSIONS: Few anesthesiologists reported receiving
      sufficient education and training in disaster medicine and public health
      preparedness. Providing education and training and enhancing related employee
      services may further bolster WTR and help to build a more capable and effective
      medical workforce for disaster response.

PMID- 28431427
TI  - Total Spinal Anesthesia Failure: Have You Assessed the Sensory Anesthesia in
      Sacral Dermatomes?
AB  - Intrathecal local anesthetic maldistribution is a well-known cause of spinal
      anesthesia failure (SAF). This could potentially result in sensory blockade
      restricted to the sacral dermatomes. We sought to determine the overall incidence
      of SAF and the role of sacral dermatomes in differentiating between total and
      partial failures. Of the 3111 spinals prospectively examined, 194 (6.2%) were
      classified as failures. Of the 72 presumed total failures based on the initial
      assessment, evaluation of the sacral dermatomes revealed sensory blockade in 32
      (44%; 95% confidence interval, 32.7%-56.6%). Sacral dermatome assessment after
      SAF may be important in safely guiding subsequent anesthetic management.

PMID- 28431428
TI  - Computational and In Vitro Experimental Investigation of Intrathecal Drug
      Distribution: Parametric Study of the Effect of Injection Volume, Cerebrospinal
      Fluid Pulsatility, and Drug Uptake.
AB  - BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the
      blood-brain barrier for pain management through its increased efficacy of pain
      relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately,
      there are limited guidelines for physicians to choose infusion or drug pump
      settings to administer therapeutic doses to specific regions of the spine or the
      brain. Although empiric trialing of intrathecal drugs is critical to determine
      the sustained side effects, currently there is no inexpensive in vitro method to
      guide the selection of spinal drug delivery parameters. The goal of this study is
      to demonstrate current computational capabilities to predict drug biodistribution
      while varying 3 parameters: (1) infusion settings, (2) drug chemistry, and (3)
      subject-specific anatomy and cerebrospinal fluid dynamics. We will discuss
      strategies to systematically optimize these 3 parameters to administer drug
      molecules to targeted tissue locations in the central nervous system. METHODS: We
      acquired anatomical data from magnetic resonance imaging (MRI) and velocity
      measurements in the spinal cerebrospinal fluid with CINE-MRI for 2 subjects. A
      bench-top surrogate of the subject-specific central nervous system was
      constructed to match measured anatomical dimensions and volumes. We generated a
      computational mesh for the bench-top model. Idealized simulations of tracer
      distribution were compared with bench-top measurements for validation. Using
      reconstructions from MRI data, we also introduced a subject-specific computer
      model for predicting drug spread for the human volunteer. RESULTS: MRI velocity
      measurements at 3 spinal regions of interest reasonably matched the simulated
      flow fields in a subject-specific computer mesh. Comparison between the idealized
      spine computations and bench-top tracer distribution experiments demonstrate
      agreement of our drug transport predictions to this physical model. Simulated
      multibolus drug infusion theoretically localizes drug to the cervical and
      thoracic region. Continuous drug pump and single bolus injection were successful
      to target the lumbar spine in the simulations. The parenchyma might be targeted
      suitably by multiple boluses followed by a flush infusion. We present potential
      guidelines that take into account drug specific kinetics for tissue uptake, which
      influence the speed of drug dispersion in the model and potentially influence
      tissue targeting. CONCLUSIONS: We present potential guidelines considering drug
      specific kinetics of tissue uptake, which determine the speed of drug dispersion
      and influence tissue targeting. However, there are limitations to this analysis
      in that the parameters were obtained from an idealized healthy patient in a
      supine position. The proposed methodology could assist physicians to select
      clinical infusion parameters for their patients and provide guidance to optimize
      treatment algorithms. In silico optimization of intrathecal drug delivery
      therapies presents the first steps toward a possible care paradigm in the future
      that is specific to personalized patient anatomy and diseases.

PMID- 28431429
TI  - It Takes a Village to Deliver Effective and Efficient Care: Team-Based
      Performance.

PMID- 28431430
TI  - Contrasting Effects of the gamma-Aminobutyric Acid Type A Receptor beta3 Subunit
      N265M Mutation on Loss of Righting Reflexes Induced by Etomidate and the Novel
      Anesthetic Barbiturate R-mTFD-MPAB: Erratum.

PMID- 28431431
TI  - An Ipsilateral Comparison of Acceleromyography and Electromyography During
      Recovery From Nondepolarizing Neuromuscular Block Under General Anesthesia in
      Humans: Erratum.

PMID- 28431432
TI  - Contrast Sensitivity and Lateral Inhibition Are Enhanced With Macular Carotenoid
      Supplementation.
AB  - Purpose: Once deposited in the retina, the so-called macular carotenoids lutein
      (L), zeaxanthin (Z), and mesozeaxanthin (MZ) have been shown to enhance visual
      performance. The purpose of our study was to investigate whether increasing
      macular pigment optical density (MPOD) could enhance lateral inhibitory
      processes, and thereby improve contrast sensitivity (CS). Methods: A total of 59
      young (18-25 years), healthy individuals participated in this 1-year, double
      masked, placebo-controlled study. MPOD was assessed via heterochromatic flicker
      photometry. Lateral inhibition sensitivity (LIS) was determined with a computer
      based, user-adjustable Hermann grid. CS (at 8 cycles/degree) was determined with
      a two-alternative, forced-choice procedure. Subjects received either the placebo
      (n = 10), 12 mg total macular carotenoids (n = 24), or 24 mg total macular
      carotenoids (n = 25). Results: MPOD, LIS, and CS increased significantly in
      treatment groups between baseline and 6 months, and between 6 and 12 months (P <
      0.05 for all) versus placebo. The relationships between changes in MPOD and both
      LIS and CS were significant at 6 and 12 months (P < 0.05 for both). Changes in CS
      and LIS over the 12-month study period were found to be significantly related (r
      = 0.41; P = 0.0014). Conclusions: Increases in MPOD led to enhanced lateral
      inhibitory processes, which correspond to improved CS. Because optical filtering
      has the same net effect on dark versus light bars, it cannot explain these
      improvements. Improvement in CS with increases in MPOD therefore appears to
      involve enhancement of the fundamental physiological systems that give rise to
      edge detection.

PMID- 28431433
TI  - Experimental Anterior Ischemic Optic Neuropathy in Diabetic Mice Exhibited Severe
      Retinal Swelling Associated With VEGF Elevation.
AB  - Purpose: Diabetes mellitus (DM) is one of the most important risk factors for
      nonarteritic anterior ischemic optic neuropathy (AION). In this study, we
      investigated for the first time the impact of experimental AION in a DM model.
      Methods: We induced a photochemical thrombosis model of AION after streptozotocin
      induced DM and performed serial optical coherence tomography (OCT), morphometric
      analyses, and VEGF levels in the retina and sera. Results: Compared with non-DM
      animals, experimental AION in DM mice led to significantly greater retinal
      swelling on day 1 and worse thinning at week 3 on OCT measurements. Greater
      retinal swelling on OCT in DM-AION eyes was associated with significantly
      increased loss of brain-specific homeobox/POU domain protein 3A (Brn3A+) retinal
      ganglion cells at week 3. In acute AION, there was greater inflammation as seen
      by an increase in ionized calcium-binding adapter molecule 1 (Iba1+)-activated
      microglia. On day 1, there was increase in vascular endothelial growth factor
      (VEGF) level in nondiabetic AION retinae and sera, but the VEGF level was the
      highest in the diabetic AION group, which decreased to nondiabetic levels after
      insulin treatment. The decrease in retinal and serum VEGF levels after insulin
      treatment correlated with a reduction in retinal swelling. Conclusions: In the
      setting of hyperglycemia, AION led to greater acute, postischemic microglial
      activation and elevation of VEGF levels, which likely contributed to greater
      retinal swelling acutely and worse retinal thinning and loss of retinal ganglion
      cells chronically. Treatment of hyperglycemia with insulin reduced VEGF levels
      and retinal swelling, consistent with the idea that VEGF is an important factor
      in postischemic swelling and that good glycemic control following AION may lead
      to better visual outcome.

PMID- 28431434
TI  - Bright Light Suppresses Form-Deprivation Myopia Development With Activation of
      Dopamine D1 Receptor Signaling in the ON Pathway in Retina.
AB  - Purpose: To determine whether dopamine receptor D1 (D1R) signaling pathway
      activation by bright light (BL) in specific retinal neuronal cell types
      contributes to inhibiting form-deprivation myopia (FDM) in mice. Methods: Mice (3
      weeks old) were raised under either normal light (NL: 100-200 lux) or BL (2500
      5000 lux) conditions with or without form deprivation. Refraction changes were
      evaluated with an eccentric infrared photorefractor, and ocular axial components
      with optical coherence tomography. The D1R antagonist, SCH39166, was
      intraperitoneally injected daily to evaluate if BL mediates declines in FDM
      development through D1R activation. Six different biomarkers of retinal neuronal
      types delineated differential distribution of D1R expression. c-Fos and
      phosphorylated tyrosine hydroxylase (p-TH) immunofluorescent staining evaluated
      D1R receptor activation and dopamine synthesis, respectively. Results: Bright
      light exposure for 4 weeks (6 hours per day) inhibited FDM development by
      reducing ocular elongation and shifting refraction toward hyperopia compared with
      changes occurring in NL. SCH39166 injections completely reversed the inhibitory
      effects of BL on both refraction and ocular elongation. Bright light increased
      the number of cells expressing p-TH and c-fos. Increases in c-fos+ cells occurred
      mainly in D1R+ bipolar cells (BCs), especially D1R+ ON-BCs. Conclusions: Bright
      light increases D1R activity in the BCs of the ON pathway, which is associated
      with less myopic shift and ocular elongation than those occurring in NL. These
      declines suggest that increased D1R activity in the ON pathway contributes to the
      BL suppression of FDM development in mice.

PMID- 28431435
TI  - Regional Extent of Peripheral Suppression in Amblyopia.
AB  - Purpose: Previously, we have mapped amblyopic eye suppression within the central
      20 degrees  of the visual field and observed a gradient of suppression that is
      strongest in central vision and weakens with increasing eccentricity. In this
      study, using a large dichoptic display, we extend our novel suppression mapping
      approach further into the periphery (from 20 degrees -60 degrees ) to assess
      whether suppression continues to decline with eccentricity or plateaus. Methods:
      Sixteen participants with amblyopia (10 with strabismus, 6 with anisometropia
      without strabismus; mean age: 37.9 +/- 11 years) and six normal observers (mean
      age: 28.3 +/- 5 years) took part. The visual stimulus (60 degrees  diameter),
      viewed from 57 cm, was composed of four concentric annuli (5 degrees  radius)
      with alternate contrast polarities starting from an eccentricity of 10 degrees .
      Each annulus was divided into eight sectors subtending 45 degrees  of visual
      angle. Participants adjusted the contrast of a single sector presented to the
      fellow eye to match the perceived contrast of the remaining stimulus elements
      that were presented to the amblyopic eye. A matching contrast that was lower in
      the fellow eye than the amblyopic eye indicated suppression. Results: Patients
      with strabismus exhibited significantly stronger interocular suppression than
      controls across all eccentricities (P = 0.01). Patients with anisometropia did
      not differ from controls (P = 0.58). Suppression varied significantly with
      eccentricity (P = 0.005) but this effect did not differ between patient groups (P
      = 0.217). Conclusions: In amblyopia, suppression is present beyond the central 10
      degrees  in patients with strabismus. Suppression becomes weaker at greater
      eccentricities and this may enable peripheral fusion that could be used by
      binocular treatment methods.

PMID- 28431437
TI  - Bright Light Blocks the Development of Form Deprivation Myopia in Mice, Acting on
      D1 Dopamine Receptors.

PMID- 28431436
TI  - Enhanced Tearing by Electrical Stimulation of the Anterior Ethmoid Nerve.
AB  - Purpose: Electrical neurostimulation enhances tear secretion, and can be applied
      to treatment of dry eye disease. Using a chronic implant, we evaluate the effects
      of stimulating the anterior ethmoid nerve on the aqueous, lipid, and protein
      content of secreted tears. Methods: Neurostimulators were implanted beneath the
      nasal mucosa in 13 New Zealand white rabbits. Stimulations (2.3-2.8 mA pulses of
      75-875 MUs in duration repeated at 30-100 Hz for 3 minutes) were performed daily,
      for 3 weeks to measure changes in tear volume (Schirmer test), osmolarity
      (TearLab osmometer), lipid (Oil-Red-O staining), and protein (BCA assay, mass
      spectrometry). Results: Stimulation of the anterior ethmoid nerve in the
      frequency range of 30 to 90 Hz increased tear volume by 92% to 133% (P <= 0.01).
      Modulating the treatment with 50% duty cycle (3 seconds of stimulation repeated
      every 6 seconds) increased tear secretion an additional 23% above continuous
      stimulation (P <= 0.01). Tear secretion returned to baseline levels within 7
      minutes after stimulation ended. Tear film osmolarity decreased by 7 mOsmol/L,
      tear lipid increased by 24% to 36% and protein concentration increased by 48% (P
      <= 0.05). Relative abundance of the lacrimal gland proteins remained the same,
      while several serum and corneal proteins decreased with stimulation (P <= 0.05).
      Conclusions: Electrical stimulation of the anterior ethmoid nerve increased
      aqueous tear volume, reduced tear osmolarity, added lipid, and increased the
      concentration of normal tear proteins. Human studies with an intranasal
      stimulator should verify these effects in patients with aqueous- and lipid
      deficient forms of dry eye disease.

PMID- 28431438
TI  - Comparison of Intact Parathyroid Hormone, Alkaline Phosphatase, Phosphate Levels
      for Diagnosing Severe Metabolic Bone Disease in Infants with Severe
      Bronchopulmonary Dysplasia.

PMID- 28431439
TI  - [Quality of and Attendance at Healthy Child Clinics in Germany].
AB  - Background For several years the German healthy child clinics program has been a
      highly appreciated preventive measure and is subject to constant development.
      However, attendance depends on the families' sociodemographic situation. Findings
      are documented in a medical checkup booklet (the so-called Gelbes Heft).
      Currently, there is no procedure to use the data collected for epidemiological
      purposes nor to evaluate the pediatric prevention measures in Germany. Methods
      Between 2011 and 2016, we recruited 3480 study participants for our population
      based cohort study LIFE Child in Leipzig. 90.6 % submitted their check-up
      booklets which were subsequently scanned, the data was digitalized and
      transmitted to a computerized form. Furthermore, data on social status (so-called
      Winkler-Index) were collected for each family using a structured questionnaire.
      The study population consisted of the families' oldest child for whom both data
      sets were available. Results The transmission of data from the check-up booklets
      was time-consuming and cost-intensive due to large datasets, uncoded diagnoses as
      well as the necessity of trained employees for transferring often illegible
      handwriting. Early diagnostic tests for children enjoy a high level of acceptance
      among all social classes. With increasing age, attendance rate decreases
      gradually. Only 83 % of the population with a lower social status attend the U9
      test. The documentation of diagnoses in the check-up booklets was implausible
      because the frequency fluctuated heavily between the different check-up time
      points. With only less than 2 %, the documentation of psychosocial difficulties
      in a child was particularly surprising Conclusion It is not possible to draw
      conclusions regarding the prevalence of target diseases from the frequency of
      documented findings in the check-up booklets. In order to make the data both
      comparable and evaluable, documentation must be digitalized in the future.

PMID- 28431440
TI  - [Valvular Diseases and Severe Heart Failure: Cooperation in the Heart Team].

PMID- 28431441
TI  - [61-Year-Old Male Patient with Recurrent Redness on the Buttocks].

PMID- 28431442
TI  - [Aortic Valve Stenosis: When to Treat Interventionally, when Surgically?]
AB  - The mainstay for the current treatment of severe aortic stenosis includes
      surgical aortic valve replacement (SAVR) and transcatheter aortic valve
      implantation (TAVI). In patients with high operative risk TAVI is established as
      first line therapy. New data on intermediate and low risk groups demonstrate at
      least non-inferiority of TAVI against SAVR, and in the near future a consistently
      rising number of transcatheter procedures may be anticipated. The purpose of this
      review is to outline the decision making process, hence to illustrate the
      diagnostic algorithm and to provide criteria for a differentiated approach
      against the background of recent data.

PMID- 28431443
TI  - [Surgical and Interventional Therapy of Mitral Valve Regurgitation].
AB  - Depending from the etiology of mitral valve pathology and surgical risk, mitral
      valve surgery is the therapy of choice for most degenerative mitral valve
      diseases. In isolated secondary mitral valve regurgitation, the indication for
      interventional or conservative therapy becomes more important. In severe left
      ventricular dysfunction heart transplantation has to be taken into consideration.
      If relevant coronary artery disease is present and bypass surgery is indicated,
      mitral valve surgery is mandatory in severe regurgitation and is subject to a
      benefit-risk evaluation in moderate regurgitation. Decision pathways take
      multiple aspects into consideration (fig. 4) like comorbidities and physical
      status of the patient as well as anatomy of the mitral valve and pathology of
      regurgitation. The choice of they should found after inspection of the patient by
      a multidisciplinary team consisting of a cardiologist, a cardiac surgeon, an
      echocardiographer and a cardiac anesthesiologist.

PMID- 28431444
TI  - [Parachute Implantation in Severe Ischemic Cardiomyopathy].

PMID- 28431445
TI  - [Near-Drowning with Good Outcome after ECMO-Therapy and Therapeutic Hypothermia
      Despite 20 Minutes of Anoxia and 16 Hours of Hypoxia].
AB  - Introduction Drowning with submersion over 10 minutes is associated with a high
      mortality. Here, we present a case, in which a good neurological outcome was
      achieved after interdisciplinary, intensive care therapy despite submersion of 20
      minutes followed by 16 hours of hypoxia. History A 19 year old man drowned in
      fresh-water. After 20 minutes submersion he was localized and salvaged from 8
      meters depth and primarily resuscitated successfully after 10 minutes. Within the
      next hour, there condition worsened by respiratory deterioration due to a massive
      capillary leak syndrome in addition to a disseminated intravascular coagulation.
      Treatment This made implantation of a veno-venous ECMO (extracorporeal membrane
      oxygenation) therapy necessary. Despite intensive care medicine including
      extracorporeal therapy a sufficient oxygenation (arterial pO2 > 60 mmHg) was
      reached only 16 hours after the drowning. Clinical Course During this time the
      patient was treated with a mild therapeutic hypothermia for cerebral protection.
      Despite the prolonged hypoxia, ECMO could be removed five days after the drowning
      and the patient was extubated after another five days without significant
      neurological deficits. Conclusion Despite submersion of 20 minutes followed by
      prolonged hypoxia, a good neurological outcome could be achieved in our patient.
      This case suggests, that tolerance of hypoxia is possibly underestimated after
      drowning.

PMID- 28431446
TI  - [Vitamin D in Clinic and Practice].
AB  - Vitamin D is unique among the vitamins, since its major source is skin synthesis
      by solar UVB exposure, whereas dietary intake plays only a minor role. In the
      general population, cutaneous vitamin D synthesis is clearly below the
      recommended amount. Dietary vitamin D does not fill this gap. Severe vitamin D
      deficiency results in rickets in infants and osteomalacia in adults. In the
      absence of endogenous vitamin D synthesis (e. g. during winter), oral supplements
      should ensure adequate daily vitamin D intake, where appropriate. This is
      particularly true for nursing home residents, non-European migrants and dark
      skinned people.

PMID- 28431447
TI  - [Return to Work after Acute Myocardial Infarction].
AB  - Vocational reintegration provides a key goal for patients after myocardial
      infarction both from social as well as from individual perspective. Return to
      work rate is determined by medical parameters such as left ventricular function,
      residual ischemia and rhythm stability, as well as by occupational requirement
      profile such as the blue or white collar work, night shifts and the way capacity.
      Psycho-social factors including depression, self-assessment of their own
      situation and pre-existing cognitive impairment to a large extent determine the
      reintegration. Optimally, re-employment should be performed immediately after
      cardiac rehabilitation in patient after uncomplicated myocardial infarction.
      After a long hospitalization phase a stepwise inclusion is recommended. In failed
      reintegration particularly in younger workers retraining should be considered.

PMID- 28431448
TI  - ?

PMID- 28431449
TI  - Peripheral and Central Glucocorticoid Signaling Contributes to Positive Energy
      Balance in Rats.
AB  - The obesity epidemic has been the target of several studies to understand its
      etiology. The pathophysiological processes that take to obesity generally relate
      to the rupture of energy balance. This imbalance can result from environmental
      and/or endogenous events. Among the endogenous events, the hypothalamic-pituitary
      adrenal axis, which promotes stress response via glucocorticoid activity, is
      considered a modulator of energy balance. However, it remains controversial
      whether the increase in plasma levels of glucocorticoids results in a positive or
      negative energy balance. Furthermore, there are no studies comparing different
      routes of administration of glucocorticoids in this context. Here, we
      investigated the effects of intraperitoneal (i.p.) or intracerebroventricular
      (i.c.v.) administration of a specific agonist for glucocorticoid receptors on
      food intake and energy expenditure in rats. Sixty-day old rats were treated with
      i.p. or i.c.v. dexamethasone. Food intake and satiety were evaluated, as well as
      locomotor activity in order to determine energy expenditure. Both i.p. and i.c.v.
      dexamethasone increased food intake and decreased energy expenditure. Moreover,
      i.c.v. dexamethasone delayed the onset of satiety. Together, these results
      confirm that central glucocorticoid signaling promotes a positive energy balance
      and supports the role of the glucocorticoid system as the underlying cause of
      psychological stress-induced obesity.

PMID- 28431450
TI  - [Livestock-Associated Methicillin-Resistant Staphylococcus aureus:
      Epidemiological Data from an Orthopaedic Department in North-West Germany].
AB  - Background MRSA represents a considerable health threat to orthopaedic patients.
      Throughout the last decade, livestock-associated MRSA emerged increasingly in
      livestock all over Europe. LA-MRSA broke the species barrier, colonizing and
      causing infections in humans. Nevertheless, to date there are no studies
      concerning livestock-associated MRSA and orthopaedic patients. Therefore, we
      aimed to investigate the prevalence of LA-MRSA in a regional orthopaedic
      department localized in an area with high-density livestock. Patients and Methods
      1544 persons were enrolled in this prospective study. Nasal swabs and
      questionnaires were collected in patients admitted to the orthopaedic hospital.
      Nasal carriage was assessed by using selective MRSA agars. MRSA-positive samples
      were spa typed. Results Overall, the prevalence of MRSA carriage was 3.3%, nearly
      all spa types were indicative for LA-MRSA. 91% of all LA-MRSA carriers had
      contact to livestock during the last 6 months before testing. Conclusion
      Livestock-associated MRSA emerged rapidly over the last few years and will
      contribute substantially to MRSA infection rates in orthopaedic hospitals.
      Livestock-associated patients must be screened before admission in order to
      control infectious complications.

PMID- 28431451
TI  - [Experience with the Hind Foot Relaxation Boot].
AB  - The goal of this paper is to report our experience with hindfoot fractures using
      our specially developed boot, with a follow-up of 557 cases. This boot works like
      the well-known Allgower-Rock ortheses (ARO), but is a hybrid between a boot and
      an orthesis. It allows full weightbearing without using crutches and completely
      protects an acutely operated hind foot fracture, hind foot arthrodesis or a hind
      foot fracture which is suitable for conservative treatment. In its first
      generation, this boot was custom made and used in 408 cases, from March 1999 to
      February 2011. This study was performed exclusively at the Department of
      Traumatology and Reconstructive Surgery in the University Centre of Orthopaedics
      and Traumatology, since 2013 at the Carl Gustav Carus University Hospital of the
      Technical University of Dresden (since 2013). The new improved second generation
      of this boot has been used in 149 patients between March 2011 and February 2016.
      This model is lighter and safer, due to an aluminium U-profile which is produced
      in one piece and interposed and fixed with 4 screws into the sole of the boot.
      The ground reaction forces are transported to the tibial head by this U-profile,
      to which the dorsal acryl shell for the calf of the Rock system is fixed with 2
      screws on both sides, including the free ventral patellar shell. This is closed
      individually by two quick fastener buckles. This modular system of the second
      generation boot is now available for all patients in Dresden. These new boots
      have replaced the use of a wheel-chair for 3 months and are especially useful in
      bilateral calcaneus fractures - which occur in about 18% of all cases. In these
      new boots, the whole sole of the boot is in contact with the ground, rather than
      a surface of 9 * 3 cm as in the Allgower-Rock ortheses. As a result, these boots
      are considered to be superior to the ARO because standing and walking without
      crutches is much more easier - even for elderly patients. In contrast to the
      Allgower-Rock ortheses, in which no ground reaction forces are transmitted to the
      free hanging foot, some ground contact in the boot is provided through the
      metatarsal heads and toes, as the foot is positioned at about 20 degrees of
      equinus. Due to these conditions, osteopenia of the foot skeleton and deficits of
      coordination are less often observed clinically after 3 months than has been the
      case with the ARO. With the Allgower-Rock orthesis for only one injured hind
      foot, the leg length must be corrected by up to 8 to 10 cm for the contralateral
      shoe sole. On the contrary, this new boot facilitates free walking. In our series
      of a total number of 557 boots in 401 patients,156 patients wore two boots due to
      bilateral hindfoot fractures. The patients' mean age was 39.9 years (14 to 80
      years), including 83.9% males. With application of low molecular weight heparin
      and lower leg compression hoses (primarily of the CCL1 type), there was no
      dislocation of the hindfoot fractures, no wound complication due to pressure in
      the boot and no deep vein thrombosis leg compression. The main indication for
      prescribing the boot was 252 bilateral calcaneal fractures. Whereas in the first
      generation fatigue fracture of the aluminium U-profile was found in 4 of 408
      (0.9%) cases. There was only one such case in the second generation (n = 149).
      The boot was worn during the with the healing time of the fractures for a mean of
      12.3 weeks in both groups.

PMID- 28431452
TI  - [Treatment Options for Neurogenic Drop Foot: A Systematic Literature Research].
AB  - Background Neurogenic drop foot may be caused by central or peripheral lesions of
      the nervous system. Depending on whether the first or second motor neuron is
      damaged, a flaccid or spastic drop foot develops. Spastic drop foot persists as a
      residual long-term complication after stroke in about 14 % of patients. Various
      conservative and surgical treatment options are available. Methods This article
      is based on a systematic literature review for medical evidence of functional
      electrical stimulation (FES) with the keywords "functional electrical stimulation
      AND drop foot" and "functional electrical stimulation AND gait AND stroke" in
      PubMed and Cochrane databases. Randomised controlled trials and cohort studies of
      the past 10 years were selected according to specific criteria. Additionally,
      four guidelines were included. Results Current guidelines provide little guidance
      for practical treatment and fail to give due consideration to new surgical
      procedures such as neural implants. In 18 randomised controlled trials on FES in
      stroke patients with drop foot, the FES-treated population showed either
      significant superiority or non-inferiority versus control. Two cohort studies
      confirmed significant improvements by FES. Conclusion The analysis demonstrates
      the importance of considering causes and severity of drop foot as well as
      patients' pre- and post-operative conditions for choosing treatment options. For
      active, high-demand patients, neural implants are valuable treatment options.

PMID- 28431453
TI  - Carboxymethyl beta-cyclodextrin as chiral selector in capillary electrophoresis:
      Enantioseparation of 16 basic chiral drugs and its chiral recognition mechanism
      associated with drugs' structural features.
AB  - Herein we present the enantioseparation of 10 cardiovascular agents and six
      bronchiectasis drugs including propranolol, carteolol, metoprolol, atenolol,
      pindolol, esmolol, bisoprolol, bevantolol, arotinolol, sotalol, clenbuterol,
      procaterol, bambuterol, tranterol, salbutamol and terbutaline sulfate using
      carboxymethyl-beta-cyclodextrin (CM-beta-CD) as chiral selector. To our
      knowledge, there is no literature about using CM-beta-CD for separating
      carteolol, esmolol, bisoprolol, bevantolol, arotinolol, procaterol, bambuterol
      and tranterol. During the course of work, changes in pH, CM-beta-CD
      concentration, buffer type and concentration were studied in relation to chiral
      resolution. Excellent enantiomeric separations were obtained for all 16
      compounds, especially for procaterol. An impressive resolution value, up to
      17.10, was obtained. In particular, most of them achieved rapid separations
      within 20 min. Given the fact that enantioseparation results rely on analytes'
      structural characters, the possible separation mechanisms were discussed. In
      addition, in order to obtain faster separation for propranolol enantiomers in
      practical application, the effective length of capillary was innovatively
      shortened from 45 to 30 cm. After the validation, the method was successfully
      applied to the enantiomeric purity determination of propranolol in the
      formulation of drug substances.

PMID- 28431454
TI  - DA-9701 improves colonic transit time and symptoms in patients with functional
      constipation: A prospective study.
AB  - BACKGROUND AND AIM: DA-9701, a newly developed prokinetic agent formulated with
      Pharbitis Semen and Corydalis Tuber, has been shown to effectively treat
      functional dyspepsia. Recently, it has also been suspected to improve
      gastrointestinal motor function. The aims of this study were to assess the effect
      of DA-9701 on colonic transit time (CTT) and symptoms of functional constipation.
      METHODS: Thirty-three patients with functional constipation based on the Rome III
      criteria were prospectively enrolled. The patients received 30-mg DA-9701 three
      times a day for 24 days. CTT was estimated initially and at the end of treatment.
      Symptoms such as spontaneous bowel movements, straining, stool form, feeling of
      incomplete emptying and anorectal blockage, abdominal discomfort and pain,
      overall defecation satisfaction, and incidence of adverse events were also
      analyzed. RESULTS: Twenty-seven patients completed the study. DA-9701 was
      associated with a significantly reduced CTT from 34.9 +/- 17.6 to 23.7 +/- 19.1 h
      (P = 0.001). Segmental CTT also significantly decreased after treatment (right
      CTT: from 16.8 [0.0-28.8] to 6.0 [0.0-25.2] hours, P < 0.001; rectosigmoid
      transit time: from 13.2 [0.0-38.4] to 6.0 [0.0-33.6] hours, P = 0.021). In
      addition, all constipation-related subjective symptoms, including spontaneous
      bowel movement frequency, significantly improved compared with those before
      treatment. Serious adverse events did not occur. CONCLUSIONS: DA-9701 accelerates
      colonic transit and safely improves symptoms in patients with functional
      constipation. Therefore, we suggest that this novel agent could help to treat
      patients with this condition.

PMID- 28431455
TI  - UHPLC-Q-TOF-MS/MS-based screening and characterization of metabolites of cnidilin
      in human liver microsomes.
AB  - Cnidilin is an active natural furocoumarin ingredient originating from well-known
      traditional Chinese medicine Radix Angelicae Dahuricae. In the present study, an
      efficient approach was developed for the screening and identification of cnidilin
      metabolites using ultra-high-performance liquid chromatography coupled to
      quadrupole time-of-flight mass spectrometry. In this approach, an on-line data
      acquisition method multiple mass defect filter combined with dynamic background
      subtraction was developed to trace all probable metabolites. Based on this
      analytical strategy, a total of 24 metabolites of cnidilin were detected in human
      liver microsomal incubation samples and the metabolic pathways were proposed. The
      results indicated that oxidation was the main biotransformation route for
      cnidilin in human liver microsomes. In addition, the specific cytochrome P450
      (CYP) enzymes involved in the metabolism of cnidilin were identified using
      chemical inhibition and CYP recombinant enzymes. The results showed that CYP1A2
      and CYP3A4 might be the major enzymes involved in the metabolism of cnidilin in
      human liver microsomes. The relationship between cnidilin and the CYP450 enzymes
      could provide us a theoretical basis of the pharmacological mechanism.

PMID- 28431456
TI  - Substance and behavioral addictions may share a similar underlying process of
      dysregulation.

PMID- 28431458
TI  - Reclaiming Our Spirits: Development and Pilot Testing of a Health Promotion
      Intervention for Indigenous Women Who Have Experienced Intimate Partner Violence.
AB  - Indigenous women are subjected to high rates of multiple forms of violence,
      including intimate partner violence (IPV), in the context of ongoing colonization
      and neo-colonization. Health promotion interventions for women who experience
      violence have not been tailored specifically for Indigenous women. Reclaiming Our
      Spirits (ROS) is a health promotion intervention designed for Indigenous women
      living in an urban context in Canada. In this paper, we describe the development
      of the intervention, results of a pilot study, and the revised subsequent
      intervention. Building on a theory-based health promotion intervention (iHEAL)
      showing promising results in feasibility studies, ROS was developed using a
      series of related approaches including (a) guidance from Indigenous women with
      research expertise specific to IPV and Indigenous women's experiences; (b)
      articulation of an Indigenous lens, including using Cree (one of the largest
      Indigenous language groups in North America) concepts to identify key aspects;
      and (c) interviews with Elders (n = 10) living in the study setting. Offered over
      6-8 months, ROS consists of a Circle, led by an Indigenous Elder, and 1:1 visits
      with a Registered Nurse, focused on six areas for health promotion derived from
      previous research. Pilot testing with Indigenous women (n = 21) produced signs of
      improvement in most measures of health from pre- to post-intervention. Women
      found the pilot intervention acceptable and helpful but also offered valuable
      suggestions for improvement. A revised intervention, with greater structure
      within the Circle and nurses with stronger knowledge of Indigenous women's
      experience and community health, is currently undergoing testing. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28431457
TI  - Precision medicine and pharmacogenetics: what does oncology have that addiction
      medicine does not?
AB  - BACKGROUND AND AIMS: Precision, personalized or stratified medicine, which
      promises to deliver the right treatment to the right patient, is a topic of
      international interest in both the lay press and the scientific literature. A key
      aspect of precision medicine is the identification of biomarkers that predict the
      response to medications (i.e. pharmacogenetics). We examined why, despite the
      great strides that have been made in biomarker identification in many areas of
      medicine, only in oncology has there been substantial progress in their clinical
      implementation. We also considered why progress in this effort has lagged in
      addiction medicine. METHODS: We compared the development of pharmacogenetic
      biomarkers in oncology, cardiovascular medicine (where developments are also
      promising) and addictive disorders. RESULTS: The first major reason for the
      success of oncologic pharmacogenetics is ready access to tumor tissue, which
      allows in-vitro testing and insights into cancer biology. The second major reason
      is funding, with cancer research receiving, by far, the largest allocation by the
      National Institutes of Health (NIH) during the past two decades. The second
      largest allocation of research funding has gone to cardiovascular disease
      research. Addictions research received a much smaller NIH funding allocation,
      despite the major impact that tobacco use, alcohol consumption and illicit drug
      use have on the public health and healthcare costs. CONCLUSIONS: Greater support
      for research on the personalized treatment of addictive disorders can be expected
      to yield disproportionately large benefits to the public health and substantial
      reductions in healthcare costs.

PMID- 28431459
TI  - Direct Growth of Al2O3 on Black Phosphorus by Plasma-Enhanced Atomic Layer
      Deposition.
AB  - Growing high-quality and uniform dielectric on black phosphorus is challenging
      since it is easy to react with O2 or H2O in ambient. In this work, we have
      directly grown Al2O3 on BP using plasma-enhanced atomic layer deposition (PEALD).
      The surface roughness of BP with covered Al2O3 film can reduce significantly,
      which is due to the removal of oxidized bubble in BP surface by oxygen plasma. It
      was also found there is an interfacial layer of PO x in between amorphous Al2O3
      film and crystallized BP, which is verified by both X-ray photoelectron
      spectroscopy (XPS) and transmission electron microscopy (TEM) measurements. By
      increasing temperature, the PO x can be converted into fully oxidized P2O5.

PMID- 28431460
TI  - Paramagnetic Intrinsic Defects in Polycrystalline Large-Area 2D MoS2 Films Grown
      on SiO2 by Mo Sulfurization.
AB  - A low-temperature electron spin resonance study has been carried out on large
      area high-purity polycrystalline two-dimensional few monolayer (ML) 2H MoS2 films
      synthesized by sulfurization of Mo layers, with intent to atomically assess
      mobility-degrading detrimental point defects. This reveals the presence of a
      distinct previously unreported anisotropic defect of axial symmetry about the c
      axis characterized by g // = 2.00145 and g ? = 2.0027, with corresponding density
      (spin S = 1/2) ~3 * 1012 cm-2 for a 4 ML thick film. Inverse correlation of the
      defect density with grain size points to a domain boundary associated defect,
      inherently incorporated during sample growth. Based on the analysis of ESR signal
      features in combination with literature data, the signal is tentatively ascribed
      to the a (di)sulfur antisite defect (S or S2 substituting for a Mo atom). Beset
      by these defects, the grain boundaries thus emerge as an intolerable threat for
      the carrier mobility and layer functionality.

PMID- 28431461
TI  - Impact of Superparamagnetic Iron Oxide Nanoparticles on Vocal Fold Fibroblasts:
      Cell Behavior and Cellular Iron Kinetics.
AB  - PURPOSE: The voice is the most important instrument of communication. Tissue
      defects in the vocal fold (VF) area lead to serious reduction in quality of life,
      but thus far, no satisfactory VF implant exists. Therefore, we aim to establish a
      functional VF implant in a rabbit model by magnetic tissue engineering (MTE)
      using superparamagnetic iron oxide nanoparticles (SPION). Hence, iron
      quantification over time as well as cell behavior studies upon SPION treatment
      are of great importance. METHODS: Rabbit VF fibroblasts (VFF) were treated with
      different concentrations of SPIONs (20, 40, and 80 MUg/cm2), and iron content was
      examined for up to 40 days using microwave plasma-atom emission spectroscopy. The
      effects of SPION treatment on VFF (adhesion, spreading, and migration), which are
      important for the formation of 3D structures, were tested. RESULTS: Cellular
      SPION quantification revealed that there was no residual iron remaining in VFFs
      after 40 days. SPIONs had a dose-dependent effect on cell adhesion, with good
      tolerability observed up to 20 MUg/cm2. Migration and spreading were not
      significantly influenced by SPION treatment up to 80 MUg/cm2. DISCUSSION AND
      CONCLUSION: To develop 3D structures, cell behavior should not be affected by
      SPION uptake. After 40 days, cells were free of iron as a result of metabolism or
      rarefication during cell division. Cell functions including adhesion, spreading,
      and migration were proven to be intact in a dose-dependent manner after SPION
      treatment, suggesting a safe usage of MTE for voice rehabilitation. Our results
      thus constitute a solid basis for a successful transfer of this technique into 3D
      constructs, in order to provide an individual and personalized human VF implant
      in the future.

PMID- 28431462
TI  - Direct Magnetic Relief Recording Using As40S60: Mn-Se Nanocomposite Multilayer
      Structures.
AB  - Processes of holographic recording of surface relief structures using As2S3:Mn-Se
      multilayer nanostructures as registering media were studied in this paper.
      Optical properties of As2S3:Mn, Se layers, and As2S3:Mn-Se multilayer
      nanostructures were investigated. Values of optical bandgaps were obtained from
      Tauc dependencies. Surface relief diffraction gratings were recorded. Direct one
      stage formation of surface relief using multilayer nanostructures is considered.
      For the first time, possibility of direct formation of magnetic relief
      simultaneous with surface relief formation under optical recording using As2S3:Mn
      Se multilayer nanostructures is shown.

PMID- 28431463
TI  - Enhanced Ferromagnetic Interaction in Modulation-Doped GaMnN Nanorods.
AB  - In this report, ferromagnetic interactions in modulation-doped GaMnN nanorods
      grown on Si (111) substrate by plasma-assisted molecular beam epitaxy are
      investigated with the prospect of achieving a room temperature ferromagnetic
      semiconductor. Our results indicate the thickness of GaN layer in each GaN/MnN
      pair, as well as Mn-doping levels, are essential for suppressing secondary phases
      as well as enhancing the magnetic moment. For these optimized samples, structural
      analysis by high-resolution X-ray diffractometry and Raman spectroscopy verifies
      single-crystalline modulation-doped GaMnN nanorods with Ga sites substituted by
      Mn atoms. Energy dispersive X-ray spectrometry shows that the average Mn
      concentration can be raised from 0.4 to 1.8% by increasing Mn fluxes without
      formation of secondary phases resulted in a notable enhancement of the saturation
      magnetization as well as coercive force in these nanorods.

PMID- 28431464
TI  - Effect of Thermomagnetic Treatment on Structure and Properties of Cu-Al-Mn Alloy.
AB  - The paper studies the influence of magnetic field on magnetic and mechanical
      properties of Cu-Mn-Al alloy under annealing. The comparative analysis of the
      magnetic field orientation impact on solid solution decomposition processes in a
      fixed annealing procedure is held using the methods of low-field magnetic
      susceptibility, specific magnetization, and microhardness test. The paper
      highlights changes in the magnetic and mechanical properties of Cu-Al-Mn alloy as
      the result of change in a critical size of forming precipitated ferromagnetic
      phase and determines correlation in the behavior of magnetic and mechanical
      properties of the alloy, depending on a critical nucleus size of forming
      precipitated ferromagnetic phase.

PMID- 28431465
TI  - Photovoltaic Properties and Ultrafast Plasmon Relaxation Dynamics of Diamond-Like
      Carbon Nanocomposite Films with Embedded Ag Nanoparticles.
AB  - Ultrafast relaxation dynamics of diamond-like carbon (DLC) films with embedded Ag
      nanoparticles (DLC:Ag) and photovoltaic properties of heterojunctions consisting
      of DLC:Ag and crystalline silicon (DLC:Ag/Si) were investigated by means of
      transient absorption (TAS) spectroscopy and photovoltaic measurements. The
      heterojunctions using both p type and n type silicon were studied. It was found
      that TAS spectra of DLC:Ag films were dependent on the used excitation
      wavelength. At wavelengths where Ag nanoparticles absorbed light most
      intensively, only DLC signal was registered. This result is in good accordance
      with an increase of the DLC:Ag/Si heterojunction short circuit current and open
      circuit voltage with the excitation wavelength in the photovoltaic measurements.
      The dependence of the TAS spectra of DLC:Ag films and photovoltaic properties of
      DLC:Ag/Si heterostructures on the excitation wavelength was explained as a result
      of trapping of the photoexcited hot charge carriers in DLC matrix. The negative
      photovoltaic effect was observed for DLC:Ag/p-Si heterostructures and positive
      ("conventional") for DLC:Ag/n-Si ones. It was explained by the excitation of hot
      plasmonic holes in the Ag nanoparticles embedded into DLC matrix. Some decrease
      of DLC:Ag/Si heterostructures photovoltage as well as photocurrent with DLC:Ag
      film thickness was observed, indicating role of the interface in the charge
      transfer process of photocarriers excited in Ag nanoparticles.

PMID- 28431466
TI  - Next-Generation Sequencing Reveals One Novel Missense Mutation in COL1A2 Gene in
      an Iranian Family with Osteogenesis imperfecta
AB  - BAckground: Osteogenesis imperfecta (OI) is a clinically and genetically
      heterogeneous disorder characterized by bone loss and bone fragility. The aim of
      this study was to investigate the variants of three genes involved in the
      pathogenesis of OI. Methods: Molecular genetic analyses were performed for
      COL1A1, COL1A2, and CRTAP genes in an Iranian family with OI. The DNA samples
      were analyzed by next-generation sequencing (NGS) gene panel and Sanger
      sequencing. Results: Five different variants were identified in COL1A1 and
      COL1A2, including two variants in COL1A1 and three variants in COL1A2. Among the
      five causative COL1A1 and COL1A2 variants, one novel variants, c.1081 G>A, was
      found in COL1A2, which was identified in two siblings. Conclusion: Our finding
      extends the variant spectrum of the COL1A2 gene and has important implications
      for genetic counseling of families. The NGS is a powerful molecular diagnostic
      strategy for OI, a heterogeneous disorder.

PMID- 28431467
TI  - Influence of Glycosylation on Interfacial Properties of Recombinant Mucins:
      Adsorption, Surface Forces, and Friction.
AB  - Interfacial properties of two brush-with-anchor mucins, C-P55 and C-PSLex, have
      been investigated at the aqueous solution/poly(methyl methacrylate) (PMMA)
      interface. Both are recombinant mucin-type fusion proteins, produced by fusing
      the glycosylated mucin part of P-selectin glycoprotein ligand-1 (PSLG-1) to the
      Fc part of a mouse immunoglobulin in two different cells. They are mainly
      expressed as dimers upon production. Analysis of the O-glycans shows that the C
      PSLex mucin has the longer and more branched side chains, but C-P55 has slightly
      higher sialic acid content. The adsorption of the mucins to PMMA surfaces was
      studied by quartz crystal microbalance with dissipation. The sensed mass,
      including the adsorbed mucin and water trapped in the layer, was found to be
      similar for these two mucin layers. Atomic force microscopy with colloidal probe
      was employed to study surface and friction forces between mucin-coated PMMA
      surfaces. Purely repulsive forces of steric origin were observed between mucin
      layers on compression, whereas a small adhesion was detected between both mucin
      layers on decompression. This was attributed to chain entanglement. The friction
      force between C-PSLex-coated PMMA is lower than that between C-P55-coated PMMA at
      low loads, but vice versa at high loads. We discuss our results in terms of the
      differences in the glycosylation composition of these two mucins.

PMID- 28431468
TI  - Sorption and Spatial Distribution of Protein Globules in Charged Hydrogel
      Particles.
AB  - We have theoretically studied the uptake of a nonuniformly charged biomolecule
      suitable for representing a globular protein or a drug by a charged hydrogel
      carrier in the presence of a 1:1 electrolyte. On the basis of the analysis of a
      physical interaction Hamiltonian including monopolar, dipolar, and Born (self
      energy) contributions derived from linear electrostatic theory of the unperturbed
      homogeneous hydrogel, we have identified five different sorption states of the
      system, from complete repulsion of the molecule to its full sorption deep inside
      the hydrogel, passing through metastable and stable surface adsorption states.
      The results are summarized in state diagrams that also explore the effects of
      varying the electrolyte concentration, the sign of the net electric charge of the
      biomolecule, and the role of including excluded-volume (steric) or hydrophobic
      biomolecule-hydrogel interactions. We show that the dipole moment of the
      biomolecule is a key parameter controlling the spatial distribution of the
      globules. In particular, biomolecules with a large dipole moment tend to be
      adsorbed at the external surface of the hydrogel, even if like-charged, whereas
      uniformly charged biomolecules tend to partition toward the internal core of an
      oppositely charged hydrogel. Hydrophobic attraction shifts the states toward the
      internal sorption of the biomolecule, whereas steric repulsion promotes surface
      adsorption for oppositely charged biomolecules or for the total exclusion of
      likely charged ones. Our results establish a guideline for the spatial
      partitioning of proteins and drugs in hydrogel carriers, tunable by the hydrogel
      charge, pH, and salt concentration.

PMID- 28431469
TI  - Enhanced Response Time of Electrowetting Lenses with Shaped Input Voltage
      Functions.
AB  - Adaptive optical lenses based on the electrowetting principle are being rapidly
      implemented in many applications, such as microscopy, remote sensing, displays,
      and optical communication. To characterize the response of these electrowetting
      lenses, the dependence upon direct current (DC) driving voltage functions was
      investigated in a low-viscosity liquid system. Cylindrical lenses with inner
      diameters of 2.45 and 3.95 mm were used to characterize the dynamic behavior of
      the liquids under DC voltage electrowetting actuation. With the increase of the
      rise time of the input exponential driving voltage, the originally underdamped
      system response can be damped, enabling a smooth response from the lens. We
      experimentally determined the optimal rise times for the fastest response from
      the lenses. We have also performed numerical simulations of the lens actuation
      with input exponential driving voltage to understand the variation in the
      dynamics of the liquid-liquid interface with various input rise times. We further
      enhanced the response time of the devices by shaping the input voltage function
      with multiple exponential rise times. For the 3.95 mm inner diameter lens, we
      achieved a response time improvement of 29% when compared to the fastest response
      obtained using single-exponential driving voltage. The technique shows great
      promise for applications that require fast response times.

PMID- 28431470
TI  - Engineering and Characterization of an Enzyme Replacement Therapy for Classical
      Homocystinuria.
AB  - Homocystinuria due to loss of cystathionine beta-synthase (CBS) causes
      accumulation of homocysteine and depletion of cysteine. Current treatments are
      suboptimal, and thus the development of an enzyme replacement therapy based on
      PEGylated human truncated CBS (PEG-CBS) has been initiated. Attenuation of
      potency was observed, which necessitated a screen of several PEG-CBS conjugates
      for their efficacy to correct and maintain the plasma metabolite profile of
      murine homocystinuria after repeated administrations interrupted with washouts.
      We found that CBS coupling with maleimide PEG inconsistently modified the enzyme.
      In contrast, the PEG-CBS conjugate with 20 kDa N-hydroxysuccinimide-PEG showed
      very little loss of potency likely due to a reproducible PEGylation resulting in
      species modified with five PEGs per subunit on average. We developed assays
      suitable for monitoring the extent of CBS PEGylation and demonstrated a
      sustainable partial normalization of homocystinuria upon continuous PEG-CBS
      administration via osmotic pumps. Taken together, we identified the PEG-CBS
      conjugate suitable for manufacturing and clinical development.

PMID- 28431471
TI  - Asthma-COPD overlap syndrome and precision medicine.

PMID- 28431472
TI  - Erratum Figure Correction: Aeroallergen sensitization and allergic disease
      phenotypes in Asia.
AB  - To the Editor: We would like to make a minor geographical correction to the map
      in the original article. The revised map is attached (Figure 1). The aeroallergen
      sensitization distributions remain accurate and this correction does not change
      the scientific conclusions of the article in any way. The authors take
      responsibility for the error.

PMID- 28431473
TI  - Structures and bioactivities of seven flavonoids from Osmanthus fragrans 'Jinqiu'
      essential oil extraction residues.
AB  - Osmanthus fragrans are well-known for their fragrance, but it is wasteful if to
      discard O. fragrans flower after extracting their essential oils. In this paper,
      we found that O. fragrans flower residues were rich in flavonoids. Six flavonoids
      and one phenylethanoid glycoside were isolated from the ethanol extract of O.
      fragrans flower residues, identified as quercetin (1), rutin (2), verbascoside
      (3), genistin (4), kaempferol (5), isorhamnetin (6) and naringin (7). In
      bioactivity study, kaempferol (IC50 = 1.43 MUg/mL) showed the best anti
      inflammatory activity. Isorhamnetin, quercetin, kaempferol, verbascoside and
      rutin (the values of IC50 were 18.30, 11.05, 16.88, 20.21 and 22.76 MUg/mL,
      respectively) showed excellent DPPH free radical scavenging activity.
      Verbascoside performed relatively well at inhibiting the growth of both CT26
      colonic carcinoma cells (IC50 = 46.87 MUg/mL) and HepG2 hepatocarcinoma cells
      (IC50 = 30.58 MUg/mL). In addition, quercetin and kaempferol showed strong anti
      proliferation activity against HepG2 cells.

PMID- 28431474
TI  - Previous hypertensive hemorrhage increases the risk for bleeding and ischemia for
      PCI patients on dual antiplatelet therapy.
AB  - OBJECTIVES: The use of antiplatelet therapy after intracerebral hemorrhage
      remains controversial, while the use of dual antiplatelet therapy (DAPT) is
      required after cardiac stenting. In this study, we examine the risk of bleeding
      and ischemic events for PCI patients with a history of hypertensive hemorrhage on
      DAPT. METHODS: A total of 128 cases and 153 controls were selected from Chinese
      patients with cardiac stenting on dual anti-platelet therapy for a single-center
      retrospective case-control study. Patients with a history of hypertensive
      hemorrhage were selected for the case group, while patients with a history of
      hypertension were chosen as control. All patients were on aspirin 100 mg and
      clopidogrel 75 mg after cardiac stenting, and were followed for a duration of 12
      48 months. The primary outcomes were intracerebral hemorrhage, major bleeding,
      and major adverse cardiovascular and cerebrovascular events. RESULTS: A history
      of previous hypertensive hemorrhage was not found to be a risk factor for
      intracerebral hemorrhage and major bleeding while on dual anti-platelet therapy.
      However, a history of either hypertensive hemorrhage or coronary artery disease
      was independently found to be risk factors for major adverse cardiovascular and
      cerebrovascular events. On sub-group analysis, patients with a history of
      hypertensive hemorrhage within 12 months were found to be at higher risk for
      bleeding on dual anti-platelet therapy, while patients with history of
      hypertensive hemorrhage outside of 12 months on dual anti-platelet therapy did
      not have the same increased risk. CONCLUSION: A history of hypertensive
      hemorrhage and coronary heart disease were two independent risk factors for major
      adverse cardiovascular and cerebrovascular events in PCI patients taking DAPT. A
      history of hypertensive hemorrhage less than 12 months had an increased risk for
      recurrent intracerebral hemorrhage and major bleeding in PCI patients taking
      DAPT.

PMID- 28431475
TI  - Validation of the Essen Stroke Risk Score in different subtypes of ischemic
      stroke.
AB  - OBJECTIVE: Predictive scores are important tools for stratifying patients based
      on their risk of future vascular events and for selecting preventive therapies.
      The aim of this study is to validate the Essen Stroke Risk Score (ESRS) for
      stratifying stroke recurrence in different subtypes of non-atrial fibrillation
      ischemic stroke in a large Chinese cohort. METHODS: Data were derived from the
      Blood pressure and clinical Outcome in Stroke Survivors registry, which includes
      a cohort of 2204 stroke patients. All patients were further classified according
      to the TOAST (Trial of Org 10 172 in Acute Stroke Treatment) criteria. We
      stratified one-year cumulative rates for stroke and composite vascular events
      using the ESRS. The predictive power of the ESRS was assessed using the area
      under the receiver-operator curves (AUC). RESULTS: Among 1699 patients included
      in the study, the AUC of ESRS was 0.58 (95% CI: 0.52-0.64) for recurrent stroke,
      whereas 0.59 (95% CI: 0.53-0.64) for composite vascular events at 1 year. In
      patients with large-artery atherosclerosis (LAA) subtype of stroke, the AUC of
      ESRS was both 0.61 (95% CI: 0.54-0.68) for recurrent stroke and composite
      vascular events. However, no significant AUC was observed in patients with small
      artery occlusion subtype of stroke. CONCLUSIONS: In patients with LAA subtype of
      non-atrial fibrillation stroke, the ESRS has moderate accuracy in stratifying the
      risk of both recurrent strokes and major vascular events within the first year.
      However, the ESRS couldn't accurately stratify the risk of recurrent strokes in
      patients with small-artery atherosclerosis subtype of non-atrial fibrillation
      stroke.

PMID- 28431476
TI  - A consensus statement for the clinical use of the renal sodium-glucose co
      transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus.
AB  - INTRODUCTION: The present review developed a clinical consensus based on a Delphi
      method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co
      transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes
      mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate
      9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic
      effects, and safety of dapaglifozin, Members also aimed to identify the patient
      most susceptible to the treatment with dapagliflozin . Expert commentary:
      Dapagliflozin is effective in lowering the plasma glucose concentration with a
      good safety profile. Dapagliflozin can be utilized in combination with all other
      antihyperglycaemic agents at all stages of the disease: however, a reduced GFR
      limits its efficacy. As for the other drugs of the class, Dapagliflozin
      positively modifies other risk factors for CV disease: these effects will be
      tested in the so far largest cardiovascular outcome trial for the SGLT2
      inhibitors so far, the DECLARE trial, which will communicate whether this class
      of drugs will be disease-modifier in patients with type 2 diabetes also in
      primary prevention.

PMID- 28431477
TI  - Duration of orthognathic-surgical treatment.
AB  - OBJECTIVE: The objective of this study was to determine the duration of
      orthognathic-surgical treatment conducted with conventional pre- and post
      surgical orthodontic treatment phases. MATERIAL AND METHODS: The study material
      was comprised of the files of 185 consecutive patients treated in Oral and
      Maxillofacial Unit, Tampere University Hospital, Finland, in 2007-2014. The files
      were reviewed and the following data was obtained: gender and age of patients,
      ICD-10 diagnosis, type of malocclusion, duration of pre- and post-surgical
      orthodontic treatment and type of operation. RESULTS: Total treatment duration
      (median) from placement of separating rings for banding until fixed orthodontic
      appliances were removed and retention period started was 31.1 months, of which
      pre-surgical orthodontics took 24.4 months and postsurgical 6.4 months. Treatment
      duration (median) was in BSSO was 32.1, LeFort 1 30.1 and bimaxillary osteotomy
      29.7 months. Orthodontic extractions were performed in 35 patients (19%). If the
      orthodontic treatment included tooth extraction, the duration of pre-surgical
      treatment was on average 10 months longer, which is a statistically highly
      significant difference (p < .001, linear regression). CONCLUSIONS: Tooth
      extractions (excluding 3rd molars) included in pre-surgical orthodontic treatment
      prolong treatment time by an average of 8-9 months.

PMID- 28431478
TI  - Successful treatment of multidrug-resistant Acinetobacter baumannii meningitis
      with ampicillin sulbactam in primary hospital.
AB  - INTRODUCTION: Acinetobacter baumannii nosocomial infections, especially those due
      to multi-drug resistant strains, are increasingly detected. We want to find the
      effective treatment measures about multi-resistant Acinetobacter baumannii
      infections through this research. METHODOLOGY: The clinical features and the
      outcomes of twelve cases of nosocomial Acinetobacter baumannii meningitis treated
      with ampicillin sulbactam and intrathecal use of amikacin are reported in primary
      hospital. All the patients had fever, neck stiffness or meningeal signs, and a
      low consciousness level, and in their cerebrospinal fluid (CSF), pleocytosis, a
      low glucose level, and an elevated protein level were noted. For all CSF isolates
      were resistant to at least two antibiotics used in empirical therapy (third and
      fourth generation cephalosporins, carbapenems or piperacillin/tazobactam). Four
      cases sputum culture prompted the growth of Acinetobacter baumannii. Two CSF
      isolates were intermediate resistant to ampicillin sulbactam, only sensitive to
      amikacin. The two patients were treated with ampicillin sulbactam and intrathecal
      use of amikacin. RESULTS: The dosages and the duration of treatment with
      ampicillin sulbactam were 2 g/1 g every 6 hours and 9-21days. Eleven patients
      were cured and one patient died of meningitis (8.3%). This patient died of severe
      respiratory Acinetobacter baumannii infection and severe sepsis. One patient had
      mild nausea and discomfort, given metoclopramide therapy. There were no serious
      side effects with the ampicillin sulbactam treatment. CONCLUSIONS: In conclusion,
      ampicillin sulbactam may be effective as therapy for meningitis caused by
      Acinetobacter baumannii resistant to imipenem and other beta-lactam drugs.
      Meanwhile, continuous lumbar external drainage and intermittent intrathecal use
      of amikacin were necessary methods.

PMID- 28431479
TI  - Pneumatic jigging: Influence of operating parameters on separation efficiency of
      solid waste materials.
AB  - This article aims to provide insights into the factors that contribute to the
      separation efficiency of solid particles. In this study, a pneumatic jigging
      technique was used to assess the separation of solid waste materials that
      consisted of copper, glass and rubber insulator. Several initial experiments were
      carried out to evaluate the strengths and limitations of the technique. It is
      found that despite some limitations of the technique, all the samples prepared
      for the experiments were successfully separated. The follow-up experiments were
      then carried out to further assess the separation of copper wire and rubber
      insulator. The effects of air flow and pulse rates on the separation process were
      examined. The data for these follow-up experiments were analysed using a sink
      float analysis technique. The analysis shows that the air flow rate was very
      important in determining the separation efficiency. However, the separation
      efficiency may be influenced by the type of materials used.

PMID- 28431480
TI  - Predictive and prognostic factors associated with soft tissue sarcoma response to
      chemotherapy: a subgroup analysis of the European Organisation for Research and
      Treatment of Cancer 62012 study.
AB  - BACKGROUND: The European Organization for Research and Treatment of Cancer
      (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin
      ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS).
      Analysis of the main study showed that combination chemotherapy improved tumor
      response and progression-free survival, but differences in overall survival (OS)
      were not statistically significant. We analyzed factors prognostic for tumor
      response and OS, and assessed histological subgroup and tumor grade as predictive
      factors to identify patients more likely to benefit from combination
      chemotherapy. METHODS: Central pathology review was performed by six reference
      pathologists. Gender, age, performance status, time from first presentation with
      sarcoma to starting palliative chemotherapy, tumor grade, histological subgroup,
      primary tumor site involvement, and sites of metastases were assessed as
      prognostic factors. RESULTS: Three hundred and ten patients were included in this
      study. Discordance between local and central pathology opinion of tumor histology
      and tumor grade was observed in 98 (32%) and 122 (39%) cases, respectively. In
      multivariate analysis, liposarcoma patients had improved tumor response compared
      to other histological subgroups, whilst patients with metastases other than lung,
      liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence
      interval (CI) 0.23-0.78; p = 0.006]. Patients with bone metastases had reduced OS
      [hazard ratio (HR) 1.56, 95% CI 1.16-2.09; p = 0.003]. By central pathology
      review, patients with undifferentiated pleomorphic sarcoma (UPS) had improved
      tumor response and OS with doxorubicin-ifosfamide compared to single-agent
      doxorubicin (OR 9.90, 95% CI 1.93-50.7 and HR 0.44, 95% CI 0.26-0.79,
      respectively). Grade III tumors had improved response with combination
      chemotherapy but there was no interaction between chemotherapy and grade on OS.
      CONCLUSIONS: Prospective central pathology review of tumor histology should be
      integrated into future STS clinical trials. Doxorubicin-ifosfamide may be most
      appropriate for young, fit patients with poorly differentiated Grade III tumors
      including UPS.

PMID- 28431481
TI  - Arab dentists' refusal to treat HIV positive patients: a survey of recently
      graduated dentists from three Arab dental schools.
AB  - OBJECTIVE: To assess intended refusal of recent graduates from three Arab dental
      schools to treat HIV + patients and factors associated with this intention.
      MATERIALS AND METHODS: In 2015, convenience samples of recent dental graduates
      were included from Libya, Egypt and the United Arab Emirates. Participants
      responded to a questionnaire assessing personal background, knowledge of oral
      manifestations and fluids transmitting HIV, perceived adequacy of training and
      self-efficacy to manage blood exposures, attitude to risk of infection, moral
      beliefs and willingness to treat HIV + patients. Logistic regression assessed
      factors associated with intended refusal to treat HIV + patients. RESULTS: The
      overall response rate was 552/710 (77.8%), mean age = 23.7 years with 41.8%
      males. The mean (SD) scores for knowledge of oral manifestations and fluids
      transmitting HIV were 5.5 (1.3)/8 and 4.2 (1.7)/7. The mean (SD) scores for
      attitude to risk of infection and moral beliefs were 2.9 (1.0)/4 and 2 (0.9)/3,
      respectively. One-third of respondents indicated intention to refuse treating HIV
      + patients. Knowledge of body fluids transmitting HIV and moral beliefs were
      associated with lower odds of refusing to treat HIV + patients (OR = 0.86 and
      0.38) whereas attitude indicating greater concern for risk of infection was
      associated with higher odds (OR = 1.54). CONCLUSIONS: One third of dentists from
      three Arab dental schools indicated they would refuse to treat HIV + patients.
      Adequate knowledge and moral beliefs reflecting professional ethics were
      associated with lower odds of refusal counterbalancing the association with
      attitude indicating increased concern for risk of infection with implications for
      dentist education and training.

PMID- 28431482
TI  - Nanozyme applications in biology and medicine: an overview.
AB  - Nanozymes, in nature, are artificial enzymes. Innovated by Ronald Breslow to
      mimic enzymes. Nanozymes have widespread applications including targeted cancer
      therapy, diagnostic medicine and bio-sensing even environmental toxicology.
      However, these applications are a novel research field in biomedicine, but are
      growing fast. Enzyme-based applications such as immune-absorbent assay (ELIZA)
      are expensive because of the complexity of producing enzymes and antibodies. Not
      only, some nanoparticles can mimic these enzymes such as superoxides, but also
      they can manipulate biological pathways directly like autophagy. These abilities
      make them a suitable alternative for both therapy and diagnosis. In this review,
      we opted on metal nanoparticles and application of this cutting edged technology
      into modern medicine.

PMID- 28431483
TI  - Bioassay-guided isolation, identification of compounds from Origanum
      rotundifolium and investigation of their antiproliferative and antioxidant
      activities.
AB  - CONTEXT: Origanum (Lamiaceae) has been used in food and pharmaceutical
      industries. OBJECTIVE: Isolation and identification of bioactive compounds from
      Origanum rotundifolium Boiss. and investigation of their antiproliferative and
      antioxidant activities. MATERIALS AND METHODS: The aerial part of O.
      rotundifolium was dried and powdered (1.0 kg +/-2.0 g) then extracted with
      hexane, ethyl acetate, methanol and water. Solvent (3 * 1 L) was used for each
      extraction for a week at room temperature. The aqueous extract was partitioned
      with ethyl acetate (3 * 1 L) to yield the water/EtOAc extract subjected to
      chromatography to isolate the active compounds. The structures of isolated
      compounds were elucidated by 1 D, 2 D NMR and LC-TOF/MS. RESULTS: Apigenin (1),
      ferulic acid (2), vitexin (3), caprolactam (4), rosmarinic acid (5), and
      globoidnan A (6) were isolated and identified. Globoidnan A (6), vitexin (3), and
      rosmarinic acid (5) revealed the excellent DPPH* scavenging effect with IC50
      values of 22.4, 31.4, 47.2 MUM, respectively. Vitexin (3) (IC50 3.6), globoidnan
      A (6) (IC50 4.6), apigenin (1) (IC50 8.9) and ferulic acid (2) exhibited more
      ABTS*+ activity than standard Trolox (IC50 13.8 MUg/mL). Vitexin (3) revealed the
      most antiproliferative activity against HeLa, HT29, C6 and Vero cells lines with
      IC50 values of 35.6, 32.5, 41.6, 46.7 (MUM), respectively. DISCUSSION AND
      CONCLUSION: Globoidnan A (6) has the most antioxidant effects on all assays. This
      has to do with the chemical structure of the compound bearing the acidic protons.
      Vitexin (3) could be a promising anticancer agent.

PMID- 28431484
TI  - WHO-5 well-being index as screening instrument for psychological comorbidity in
      patients with temporomandibular disorder.
AB  - OBJECTIVES: The aim of the study was to compare the WHO-Five Well-Being Index
      (WHO-5) with the Oral Health Impact Profile-49 (OHIP-49) questionnaire as
      screening tools to detect psychological comorbidity in TMDs. METHODS: A TMD group
      (92 patients, 42.8 +/- 17.1 yrs) and a control group (90 patients of the
      Department of Prosthetic Dentistry, 38.9 +/- 10.1 yrs) completed the WHO-5 and
      the OHIP-49 questionnaire. RESULTS: The patients with TMD reported significantly
      greater OHIP-49 sum scores than controls (47.5 +/- 34.7 vs. 7.7 +/- 12.1; p <
      0.001). The mean raw score of the WHO-5 was significantly less, with 45.6 +/-
      20.6 points for patients with TMD than the 73.2 +/- 15.6 points found for
      controls (p < 0.001). The OHIP sum score and the WHO-5 raw score were
      significantly associated (r = 0.705, p < 0.001). Both instruments exhibited
      excellent internal consistency (Cronbach's alpha = 0.967 and 0.883,
      respectively). CONCLUSIONS: WHO-5 proved to be an effective and economic
      screening instrument to detect psychological comorbidity in TMDs. Implementing
      WHO-5 in standard care could contribute to more individualized interdisciplinary
      psychotherapy and/or functional therapy.

PMID- 28431485
TI  - Efficacy of golimumab in Belgian patients with active rheumatoid arthritis
      despite treatment with non-biologic disease-modifying anti-rheumatic drugs: sub
      analysis of the GO-MORE study.
AB  - OBJECTIVES: The GO-MORE trial (NCT00975130) was a phase 3 study in 40 countries
      evaluating the efficacy and safety of golimumab as add-on therapy in biologic
      naive adults with active rheumatoid arthritis despite stable treatment with
      disease-modifying anti-rheumatic drugs. To inform local practice in Belgium and
      examine the role of baseline disease activity in treatment response, we compared
      the efficacy of golimumab in the Belgian subpopulation and the rest of the world.
      METHODS: Baseline disease activity and six-month efficacy rates in the GO-MORE
      trial were compared for the Belgian subpopulation and the rest of the world by t
      tests and chi-squared tests. RESULTS: Except for functional impairment, all
      measures of baseline disease activity were significantly lower (p < 0.0001) in
      the Belgian population (n = 123) than in the rest of the world (n = 3157). At
      month six, the rate of good/moderate EULAR response was similar in Belgium and
      the rest of the world (78.9% vs. 82.2%; p = 0.34), but remission rates were
      higher in Belgium according to the DAS28-ESR (43.1% vs. 23.2%; p < 0.0001) and
      Simplified Disease Activity Index (22.0% vs. 13.8%; p = 0.01). Rates of low DAS28
      ESR disease activity were also higher in Belgium (54.5% vs. 36.8%; p < 0.0001).
      Within the Belgian subpopulation, efficacy measures were not significantly
      different between patients with moderate (n = 73) and high baseline activity (n =
      49). Rates of functional impairment at month six did not differ between the two
      populations. CONCLUSION: In the Belgian population of the GO-MORE trial, baseline
      disease activity was lower and six-month remission rates were higher than in the
      rest of the world.

PMID- 28431486
TI  - Evaluating the operational risks of biomedical waste using failure mode and
      effects analysis.
AB  - The potential problems and risks of biomedical waste generation have become
      increasingly apparent in recent years. This study applied a failure mode and
      effects analysis to evaluate the operational problems and risks of biomedical
      waste. The microbiological contamination of biomedical waste seldom receives the
      attention of researchers. In this study, the biomedical waste lifecycle was
      divided into seven processes: Production, classification, packaging,
      sterilisation, weighing, storage, and transportation. Twenty main failure modes
      were identified in these phases and risks were assessed based on their risk
      priority numbers. The failure modes in the production phase accounted for the
      highest proportion of the risk priority number score (27.7%). In the packaging
      phase, the failure mode 'sharp articles not placed in solid containers' had the
      highest risk priority number score, mainly owing to its high severity rating. The
      sterilisation process is the main difference in the treatment of infectious and
      non-infectious biomedical waste. The failure modes in the sterilisation phase
      were mainly owing to human factors (mostly related to operators). This study
      increases the understanding of the potential problems and risks associated with
      biomedical waste, thereby increasing awareness of how to improve the management
      of biomedical waste to better protect workers, the public, and the environment.

PMID- 28431487
TI  - Design and fuzzy logic control of an active wrist orthosis.
AB  - People who perform excessive wrist movements throughout the day because of their
      professions have a higher risk of developing lateral and medial epicondylitis. If
      proper precautions are not taken against these diseases, serious consequences
      such as job loss and early retirement can occur. In this study, the design and
      control of an active wrist orthosis that is mobile, powerful and lightweight is
      presented as a means to avoid the occurrence and/or for the treatment of
      repetitive strain injuries in an effective manner. The device has an
      electromyography-based control strategy so that the user's intention always comes
      first. In fact, the device-user interaction is mainly activated by the
      electromyography signals measured from the forearm muscles that are responsible
      for the extension and flexion wrist movements. Contractions of the muscles are
      detected using surface electromyography sensors, and the desired quantity of the
      velocity value of the wrist is extracted from a fuzzy logic controller. Then, the
      actuator system of the device comes into play by conveying the necessary motion
      support to the wrist. Experimental studies show that the presented device
      actually reduces the demand on the muscles involved in repetitive strain injuries
      while performing challenging daily life activities including extension and
      flexion wrist motions.

PMID- 28431488
TI  - Core vocabulary of young children with Down syndrome.
AB  - The aim of this study was to develop a core vocabulary list for young children
      with intellectual disabilities between 2 and 7 years of age because data from
      this population are lacking in core vocabulary literature. Children with Down
      syndrome are considered one of the most valid reference groups for researching
      developmental patterns in children with intellectual disabilities; therefore,
      spontaneous language samples of 30 Dutch children with Down syndrome were
      collected during three different activities with multiple communication partners
      (free play with parents, lunch- or snack-time at home or at school, and speech
      therapy sessions). Of these children, 19 used multimodal communication, primarily
      manual signs and speech. Functional word use in both modalities was transcribed.
      The 50 most frequently used core words accounted for 67.2% of total word use; 16
      words comprised core vocabulary, based on commonality. These data are consistent
      with similar studies related to the core vocabularies of preschoolers and
      toddlers with typical development, although the number of nouns present on the
      core vocabulary list was higher for the children in the present study. This
      finding can be explained by manual sign use of the children with Down syndrome
      and is reflective of their expressive vocabulary ages.

PMID- 28431489
TI  - Apathy in amyotrophic lateral sclerosis: insights from Dimensional Apathy Scale.
AB  - OBJECTIVES: Apathy is associated with cognitive decline and worse survival in
      amyotrophic lateral sclerosis (ALS); an accurate evaluation of this aspect is
      relevant in clinical settings. The aims of this study are to evaluate the
      prevalence of apathy in a large ALS sample, using published diagnostic criteria,
      and to explore the psychometric properties, the sensitivity and the specificity
      of the Dimensional Apathy Scale (DAS) as a screening tool for apathy. METHODS:
      One hundred and thirty-one patients underwent clinical interview based on
      diagnostic criteria for apathy, DAS, Apathy Evaluation Scale, and assessment of
      depression, global cognitive functioning, and non-verbal intelligence. RESULTS:
      According to diagnostic criteria, apathy occurred in 28.2% of the patients. The
      DAS showed high consistency, convergent, and discriminant validities. Apathetic
      and non-apathetic patients significantly differed on total DAS and executive and
      Behavioral/Cognitive Initiation subscales, indicating good criterion validity.
      Receiver operating characteristics analysis, considering diagnostic criteria for
      apathy as gold standard, revealed that a score of 26/27 was an optimal cut-off
      score for the identification of apathy. CONCLUSIONS: The DAS is a valid screening
      tool for apathy and its aspects in ALS through limiting the impact of physical
      disability. Executive and behavioral/cognitive aspects of apathy, rather than
      emotional aspects, are more frequent in ALS.

PMID- 28431490
TI  - New challenges in therapeutic vaccines against HIV infection.
AB  - INTRODUCTION: There is a growing interest in developing curative strategies for
      HIV infection. Therapeutic vaccines are one of the most promising approaches. We
      will review the current knowledge and the new challenges in this research field.
      Areas covered: PubMed and ClinicalTrial.gov databases were searched to review the
      progress and prospects for clinical development of immunotherapies aimed to cure
      HIV infection. Dendritic cells (DC)-based vaccines have yielded the best results
      in the field. However, major immune-virologic barriers may hamper current vaccine
      strategies. We will focus on some new challenges as the antigen presentation by
      DCs, CTL escape mutations, B cell follicle sanctuary, host immune environment
      (inflammation, immune activation, tolerance), latent reservoir and the lack of
      surrogate markers of response. Finally, we will review the rationale for
      designing new therapeutic vaccine candidates to be used alone or in combination
      with other strategies to improve their effectiveness. Expert commentary: In the
      next future, the combination of DCs targeting candidates, inserts to redirect
      responses to unmutated parts of the virus, adjuvants to redirect responses to
      sanctuaries or improve the balance between activation/tolerance (IL-15, anti-PD1
      antibodies) and latency reversing agents could be necessary to finally achieve
      the remission of HIV-1 infection.

PMID- 28431491
TI  - Fluoride varnishes containing sodium trimetaphosphate reduce enamel
      demineralization in vitro.
AB  - OBJECTIVE: This study evaluated the effects of fluoride varnishes containing
      sodium trimetaphosphate (TMP) on bovine enamel demineralization in vitro.
      MATERIAL AND METHODS: Enamel bovine discs were randomly assigned into six groups
      (n = 20/group): placebo, 2.5% NaF, 2.5% NaF/5% TMP, 5% NaF, 5% NaF/5% TMP, and a
      commercial formulation (Duraphat, 5% NaF). Varnishes were applied on all enamel
      discs and kept for 6 h. Loosely and firmly bound fluoride formed on/in enamel
      after treatment were analyzed in 10 discs from each group. The other 10 discs
      were subjected to a pH-cycling regimen for 7 days, and analyzed for surface (SH)
      and cross-sectional hardness (DeltaKHN), as well as for loosely and firmly bound
      fluoride in/on enamel. Data were analyzed by analysis of variance (ANOVA)
      followed by Student-Newman-Keuls' test (p < .05). RESULTS: The lowest SH change
      and DeltaKHN were observed for the 5%NaF/5%TMP varnish, which was significantly
      different from all the other groups. Both fluoridated varnishes containing TMP
      promoted significantly lower SH change and DeltaKHN when compared with their
      counterparts without TMP. Loosely and firmly bound fluoride was significantly
      lower in groups treated with varnishes containing TMP. CONCLUSION: TMP and
      fluoride added to varnishes have a synergistic effect against enamel
      demineralization in vitro.

PMID- 28431492
TI  - Anti-drug antibodies in Colombian patients with rheumatoid arthritis treated with
      Enbrel vs Etanar - Preliminary report.
AB  - The present study was undertaken to detect antibodies against etanercept (ETN) in
      a group of Colombian patients with rheumatoid arthritis (RA) and being treated
      with Enbrel(r) vs. Etanar(r). From these patients with RA, clinical and
      laboratory data were collected and serum taken for anti-drug antibody (ADAb)
      analysis. Samples from 32 patients (16 who had been treated with Enbrel(r) and 16
      with Etanar(r)) were analyzed. Positive sera for ADAb were found in six of the 32
      subjects (18.7%); five (31.2%) in the Enbrel(r) group and one (6.25%) in the
      Etanar(r) group. Patients under treatment with Enbrel(r) registered a longer
      disease duration than patients being treated with Etanar(r) (15.4 years vs. 10.98
      years, p = 0.175) as well as a longer average treatment with the drug (45.7 vs.
      23.9 months, p = 0.052). The percentage of patients with disease activity defined
      as a disease activity score by C-reactive protein (DAS28-CRP) scores >=2.3 was
      higher in those patients with positive sera in the enzyme-linked immunosorbent
      assay (ELISA) (66.7%) than in those with negative sera (34.6%). A logistic
      regression test revealed that the higher the DAS28-CRP value, the higher the
      ELISA absorbance value. The results showed evidence of greater frequency of ADAb
      in patients treated with ETN than has been reported to date. Greater disease
      activity was seen in those patients in whose serum ADAb had been detected.
      Significant differences were found between the positive ELISA for the group of
      patients treated with Enbrel(r) compared to those treated with Etanar(r). Some of
      the factors that could explain this difference are the length of the treatment
      time with the drug, the commercial ELISA kit used to detect ADAb, or the
      immunogenicity itself of each product.

PMID- 28431493
TI  - Pan-intestinal capsule endoscopy in patients with postoperative Crohn's disease:
      a pilot study.
AB  - BACKGROUND: Patients are at increased risk of disease recurrence after surgical
      treatment of Crohn's disease. Endoscopic detection of postoperative, ileo-colonic
      inflammation is well established, but the potential of pan-intestinal endoscopy
      is yet unknown. METHODS: This prospective multicenter pilot study assessed the
      value of pan-intestinal capsule endoscopy using a colon capsule endoscope for the
      detection of inflammatory recurrence of Crohn's disease. Patients who had been
      operatively treated for Crohn's disease were included. Colon capsule endoscopy
      was performed 4-8 weeks (d1) and 4-8 months (d2) postoperatively together with
      ileo-colonoscopy at d2 using a modified Ruttgeerts index for evaluating disease
      activity. RESULTS: Twenty-two patients were included into this study. At d1,
      significant disease activity (Ruttgeerts index >=2) was detected in 3/16 (19%) of
      the patients. At d2, half of the patients (6/12) showed active disease, whereas
      ileo-colonoscopy revealed significant inflammation in 5/15 (33%). All patients
      rated as having active disease by ileo-colonoscopy had been revealed by PICE as
      well. These findings influenced the medical treatment in every case. CONCLUSION:
      Pan-intestinal capsule endoscopy seems to be feasible in the postoperative
      surveillance of Crohn's disease. Disease activity is reliably detected.
      Especially, the findings in the small bowl might be a significant advantage in
      comparison to ileo-colonoscopy, as they can have significant impact on clinical
      management. Further studies with a larger number of patients are needed to
      confirm these findings and might lead to a replacement of the flexible ileo
      colonoscopy with pan-intestinal capsule endoscopy in this indication in the
      future.

PMID- 28431494
TI  - Surgical results of modified canal wall down tympanoplasty.
AB  - CONCLUSION: Patients with mastoiditis and chronic suppurative otitis media which
      has small mastoids that make them ideal candidates for modified canal wall down
      mastoidectomy (MCWD) which contributes to a dry and spacious ear and the
      maintaining and improving hearing. OBJECTIVES: To evaluate surgical outcomes for
      chronic otitis media underwent MCWD. METHODS: A clinical retrospective study was
      performed on 47 ears with chronic otitis media which has relatively limited attic
      lesions have the small, sclerotic and hypocellular mastoids according to the
      preoperative high-resolution CT scan of the temporal bone that underwent MCWD and
      32 ears with typical canal wall down operation form January 2010 to January 2016.
      RESULTS: In the MCWD group, the mean preoperative air conduction (AC) threshold
      of 38.2 +/- 1.1 dB was lowered to 31.0 +/- 0.8 dB postoperatively (p < .01). The
      mean pre- and postoperative air-bone gaps (ABG) of all patients were 16.0 +/- 1.0
      dB and 9.6 +/- 0.8 dB, respectively. In the canal wall down group, the mean
      preoperative AC threshold of 37.2 +/- 1.0 dB was lowered to 32.8 +/- 0.9 dB
      postoperatively (p < .01). The mean pre- and postoperative air-bone gap was
      reduced with 4.4 +/- 0.4 dB (p < .01). There was statistical difference in
      hearing improvement between the modified canal wall down and the canal wall down
      group (p < .05).

PMID- 28431496
TI  - The phylogeny of fossil whip spiders.
AB  - BACKGROUND: Arachnids are a highly successful group of land-dwelling arthropods.
      They are major contributors to modern terrestrial ecosystems, and have a deep
      evolutionary history. Whip spiders (Arachnida, Amblypygi), are one of the smaller
      arachnid orders with ca. 190 living species. Here we restudy one of the oldest
      fossil representatives of the group, Graeophonus anglicus Pocock, 1911 from the
      Late Carboniferous (Duckmantian, ca. 315 Ma) British Middle Coal Measures of the
      West Midlands, UK. Using X-ray microtomography, our principal aim was to resolve
      details of the limbs and mouthparts which would allow us to test whether this
      fossil belongs in the extant, relict family Paracharontidae; represented today by
      a single, blind species Paracharon caecus Hansen, 1921. RESULTS: Tomography
      reveals several novel and significant character states for G. anglicus; most
      notably in the chelicerae, pedipalps and walking legs. These allowed it to be
      scored into a phylogenetic analysis together with the recently described
      Paracharonopsis cambayensis Engel & Grimaldi, 2014 from the Eocene (ca. 52 Ma)
      Cambay amber, and Kronocharon prendinii Engel & Grimaldi, 2014 from Cretaceous
      (ca. 99 Ma) Burmese amber. We recovered relationships of the form ((Graeophonus
      (Paracharonopsis + Paracharon)) + (Charinus (Stygophrynus (Kronocharon (Charon
      (Musicodamon + Paraphrynus)))))). This tree largely reflects Peter Weygoldt's
      1996 classification with its basic split into Paleoamblypygi and Euamblypygi
      lineages; we were able to score several of his characters for the first time in
      fossils. Our analysis draws into question the monophyly of the family
      Charontidae. CONCLUSIONS: Our data suggest that Graeophonus is a crown group
      amblypygid, and falls within a monophyletic Paleoamblypgi clade, but outside the
      family Paracharontidae (= Paracharonopsis + Paracharon). Our results also suggest
      a new placement for the Burmese amber genus Kronocharon, a node further down from
      its original position. Overall, we offer a broad phylogenetic framework for both
      the fossil and Recent whip spiders against which future discoveries can be
      tested.

PMID- 28431495
TI  - Iron-regulated small RNA expression as Neisseria gonorrhoeae FA 1090 transitions
      into stationary phase growth.
AB  - BACKGROUND: For most pathogens, iron (Fe) homeostasis is crucial for maintenance
      within the host and the ability to cause disease. The primary transcriptional
      regulator that controls intracellular Fe levels is the Fur (ferric uptake
      regulator) protein, which exerts its action on transcription by binding to a
      promoter-proximal sequence termed the Fur box. Fur-regulated transcriptional
      responses are often fine-tuned at the post-transcriptional level through the
      action of small regulatory RNAs (sRNAs). Consequently, identifying sRNAs
      contributing to the control of Fe homeostasis is important for understanding the
      Fur-controlled bacterial Fe-response network. RESULTS: In this study, we
      sequenced size-selected directional libraries representing sRNA samples from
      Neisseria gonorrhoeae strain FA 1090, and examined the Fe- and temporal
      regulation of these sRNAs. RNA-seq data for all time points identified a pool of
      at least 340 potential sRNAs. Differential analysis demonstrated that expression
      appeared to be regulated by Fe availability for at least fifteen of these sRNAs.
      Fourteen sRNAs were induced in high Fe conditions, consisting of both cis and
      trans sRNAs, some of which are predicted to control expression of a known
      virulence factor, and one SAM riboswitch. An additional putative cis-acting sRNA
      was repressed by Fe availability. In the pathogenic Neisseria species, one sRNA
      that contributes to Fe-regulated post-transcriptional control is the Fur
      repressible sRNA NrrF. The expression of five Fe-induced sRNAs appeared to be at
      least partially controlled by NrrF, while the remainder was expressed
      independently of NrrF. The expression of the 14 Fe-induced sRNAs also exhibited
      temporal control, as their expression levels increased dramatically as the
      bacteria entered stationary phase. CONCLUSIONS: Here we report the temporal
      expression of Fe-regulated sRNAs in N. gonorrhoeae FA 1090 with several appearing
      to be controlled by the Fe-repressible sRNA NrrF. Temporal regulation of these
      sRNAs suggests a regulatory role in controlling functions necessary for survival,
      and may be important for phenotypes often associated with altered growth rates,
      such as biofilm formation or intracellular survival. Future functional studies
      will be needed to understand how these regulatory sRNAs contribute to gonococcal
      biology and pathogenesis.

PMID- 28431497
TI  - Effect of ensiled mulberry leaves and sun-dried mulberry fruit pomace on the
      fecal bacterial community composition in finishing steers.
AB  - BACKGROUND: Here, we aimed to investigate the effects of ensiled mulberry leaves
      (EML) and sun-dried mulberry fruit pomace (SMFP) on fecal bacterial communities
      in Simmental crossbred finishing steers. To this end, the steers were reared on a
      standard TMR diet, standard diet containing EML, and standard diet containing
      SMFP. The protein and energy levels of all the diets were similar. Illumina MiSeq
      sequencing of the V4 region of the 16S rRNA gene and quantitative real-time PCR
      were used to analyze and detect the fecal bacterial community. RESULTS: Most of
      the sequences were assigned to Firmicutes (56.67%) and Bacteroidetes (35.90%),
      followed by Proteobacteria (1.87%), Verrucomicrobia (1.80%) and Tenericutes
      (1.37%). The predominant genera were 5-7 N15 (5.91%), CF231 (2.49%), Oscillospira
      (2.33%), Paludibacter (1.23%) and Akkermansia (1.11%). No significant differences
      were observed in the numbers of Firmicutes (p = 0.28), Bacteroidetes (p = 0.63),
      Proteobacteria (p = 0.46), Verrucomicrobia (p = 0.17), and Tenericutes (p = 0.75)
      populations between the treatment groups. At the genus level, genera classified
      with high abundance (more than 0.1%) belonged primarily to Bacteroidetes and
      Firmicutes. Furthermore, no differences were observed at the genus level: 5-7
      N15, CF231, Oscillospira, Paludibacter, and Akkermansia (p > 0.05 in all cases),
      except that rc4-4 was lower in the CON and SMFP groups than in the EML group (p =
      0.02). There were no significant differences in the richness estimate and
      diversity indices between the groups (p > 0.16), and the different diets did not
      significantly influence most selected fecal bacterial species (p > 0.06), except
      for Ruminococcus albus, which was higher in the EML group (p < 0.01) and
      Streptococcus bovis, which was lower in the CON group (p < 0.01) relative to the
      other groups. CONCLUSIONS: In conclusion, diets supplemented with EML and SMFP
      have little influence on the fecal bacterial community composition in finishing
      steers.

PMID- 28431498
TI  - Migrant workers in Italy: an analysis of injury risk taking into account
      occupational characteristics and job tenure.
AB  - BACKGROUND: Migrants resident in Italy exceeded 5 million in 2015, representing
      8.2% of the resident population. The study of the mechanisms that explain the
      differential health of migrant workers (as a whole and for specific
      nationalities) has been identified as a priority for research. The international
      literature has shown that migrant workers have a higher risk of total and fatal
      injury than natives, but some results are conflicting. The aim of this paper is
      to study the injury risk differentials between migrants, born in countries with
      strong migratory pressure (SMPC), and workers born in high income countries
      (HIC), taking into account individual and firm characteristics and job tenure. In
      addition to a comprehensive analysis of occupational safety among migrants, the
      study focuses on Moroccans, the largest community in Italy in the years of the
      analysis. METHODS: Using the Work History Italian Panel-Salute integrated
      database, only contracts of employment in the private sector, starting in the
      period between 2000 and 2005 and held by men, were selected. The analysis focused
      on economic sectors with an important foreign component: engineering,
      construction, wholesale and retail trade, transportation and storage. Injury
      rates were calculated using a definition of serious occupational injuries based
      on the type of injury. Incidence rate ratios (IRR) were calculated using a
      Poisson distribution for panel data taking into account time-dependent variables.
      RESULTS: Injury rates among SMPC workers were higher than for HIC workers in
      engineering (15.61 0/00 py vs. 8.92 0/00 py), but there were no significant
      differences in construction (11.21 vs. 10.09), transportation and storage (7.82
      vs. 7.23) and the wholesale and retail sectors (4.06 vs. 4.67). Injury rates for
      Moroccans were higher than for both HIC and total migrant workers in all economic
      sectors considered. The multivariate analysis revealed an interaction effect of
      job tenure among both SMPC and Moroccan workers in the construction sector, while
      in the wholesale and retail trade sector an interaction effect of job tenure was
      only observed among Moroccan workers. CONCLUSIONS: Migrant workers have higher
      occupational injury rates than Italians in the engineering and construction
      sectors, after two years of experience within the job. Generally the risk
      differentials vary depending on the nationality and economic sector considered.
      The analysis of injury risk among migrant workers should be restricted to serious
      injuries; furthermore, job tenure must be taken into account.

PMID- 28431499
TI  - Asthma-COPD overlap syndrome (ACOS) in primary care of four Latin America
      countries: the PUMA study.
AB  - BACKGROUND: Asthma-COPD overlap syndrome (ACOS) prevalence varies depending on
      the studied population and definition criteria. The prevalence and clinical
      characteristics of ACOS in an at-risk COPD primary care population from Latin
      America was assessed. METHODS: Patients >=40 years, current/ex-smokers and/or
      exposed to biomass, attending routine primary care visits completed a
      questionnaire and performed spirometry. COPD was defined as post-bronchodilator
      forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) < 0.70; asthma
      was defined as either prior asthma diagnosis or wheezing in the last 12 months
      plus reversibility (increase in post-bronchodilator FEV1 or FVC >=200 mL and
      >=12%); ACOS was defined using a combination of COPD with the two asthma
      definitions. Exacerbations in the past year among the subgroups were evaluated.
      RESULTS: One thousand seven hundred forty three individuals completed the
      questionnaire, 1540 performed acceptable spirometry, 309 had COPD, 231 had prior
      asthma diagnosis, and 78 asthma by wheezing + reversibility. ACOS prevalence in
      the total population (by post-bronchodilator FEV1/FVC < 0.70 plus asthma
      diagnosis) was 5.3 and 2.3% by post-bronchodilator FEV1/FVC < 0.70 plus wheezing
      + reversibility. In the obstructive population (asthma or COPD), prevalence rises
      to 17.9 and 9.9% by each definition, and to 26.5 and 11.3% in the COPD
      population. ACOS patients defined by post-bronchodilator FEV1/FVC < 0.7 plus
      wheezing + reversibility had the lowest lung function measurements. Exacerbations
      for ACOS showed a prevalence ratio of 2.68 and 2.20 (crude and adjusted, p <
      0.05, respectively) (reference COPD). CONCLUSIONS: ACOS prevalence in primary
      care varied according to definition used. ACOS by post-bronchodilator FEV1/FVC <
      0.7 plus wheezing + reversibility represents a clinical phenotype with more
      frequent exacerbations, which is probably associated with a different management
      approach.

PMID- 28431500
TI  - Foot length, chest and head circumference measurements in detection of Low birth
      weight neonates in Mekelle, Ethiopia: a hospital based cross sectional study.
AB  - BACKGROUND: Low birth weight (Birth weight < 2500 g) is a leading cause of
      prenatal and neonatal deaths. The early identification of Low birth weight (LBW)
      neonates is essential for any comprehensive initiative to improve their chance of
      survival. However, a large proportion of births in developing countries take
      place at home and birth weight statistics are not available. Therefore, there is
      a need to develop simple, inexpensive and practical methods to identify low birth
      weight (LBW) neonates soon after birth. METHODS: This is a hospital based cross
      sectional study. Four hundred twenty two (422) live born neonates were included
      and anthropometric measurements were carried out within 24 h of birth by three
      trained nurses. Birth weight was measured by digital scale. Head and chest
      circumference were measured by using non extendable measuring tape and foot
      length with hard transparent plastic ruler. Data was entered into SPSS version 20
      for analysis. Characteristics of study participants were analyzed using
      descriptive statistics such as frequency and percentage for categorical data and
      mean and standard deviation for continuous data. Correlation with birth weight
      using Pearson's correlation coefficient and linear regression were used to
      identify the association between dependent and independent variables. Receiver
      operating characteristic (ROC) curve was used to evaluate accuracy of the
      anthropometric measurements to predict LBW. RESULTS: The prevalence of low birth
      weight was found to be 27%. All anthropometric measurements had a positive
      correlation with birth weight, chest circumference attaining the highest
      correlation with birth weight (r = 0.85) and foot length had the weakest
      correlation (r = 0.74). Head circumference had the highest predictive value for
      birth weight (AUC = 0.93) followed by Chest circumference (AUC = 0.91). A cut off
      point of chest circumference 30.15 cm had 84.2% sensitivity, 85.4% specificity
      and diagnostic accuracy (P < 0.001). A cut off point of head circumference 33.25
      had the highest positive predictive value (77%). CONCLUSION: Chest circumference
      and head circumference were found to be better surrogate measurements to identify
      low birth weight neonates.

PMID- 28431501
TI  - Outcomes after early and delayed rehabilitation for exacerbation of chronic
      obstructive pulmonary disease: a nationwide retrospective cohort study in Japan.
AB  - BACKGROUND: The effectiveness of early pulmonary rehabilitation (PR) for
      exacerbation of chronic obstructive pulmonary disease (COPD) remains
      controversial. The present study aimed to compare the outcomes between early and
      delayed PR for exacerbation of COPD, using a national inpatient database.
      METHODS: Using the Japanese Diagnosis Procedure Combination database, we examined
      patients who were transported to hospital for exacerbation of COPD, received PR
      during hospitalisation, and were discharged to their home. The patients were
      divided into those who received early PR (defined as PR starting within 48 h of
      admission) and those who received delayed PR. The outcomes included 90-day
      readmission, length of stay (LOS), and activities of daily living (Barthel index
      >=15) at discharge. Multiple imputation was used for missing data. To assess the
      associations between early PR and the outcomes, we used risk-adjusted treatment
      effects and instrumental variable methods. RESULTS: We identified 12,572 eligible
      patients, including 8459 patients with delayed PR and 4113 with early PR. In the
      risk-adjusted treatment effect models, the early PR group had lower proportion of
      90-day readmission (risk difference, -3.4%; 95% CI, -5.7% to -1.5%) and shorter
      LOS (-9.8 days; 95% CI, -10.8 days to -8.7 days) than the delayed PR group. There
      was no significant difference in activities of daily living at discharge between
      the two groups. The instrumental variable analyses showed similar results.
      CONCLUSIONS: In this national database study, early PR was associated with
      reduced 90-day readmission and shortened LOS in patients with exacerbation of
      COPD.

PMID- 28431502
TI  - Inequalities in health care utilization for common childhood illnesses in
      Ethiopia: evidence from the 2011 Ethiopian Demographic and Health Survey.
AB  - BACKGROUND: Globally, 5.9 million children under the age of five died in 2015.
      More than half and almost one-third of those deaths occurred in sub-Saharan
      Africa and South Asia, respectively. Diarrhea and Pneumonia, which were the major
      causes of the problem, accounted for more than two million deaths of the world's
      youngest children every year. Like other developing countries, child health
      services utilization is low in Ethiopia. The aim of this study was to identify
      the determinant factors for the inequalities in medical treatment seeking
      behavior for common childhood illnesses in Ethiopia. METHODS: Data were obtained
      from the Ethiopian Demographic and Health Survey (EDHS) 2011. All children who
      had diarrhea, cough, and fever in the 2 weeks preceding the survey were included.
      A total of 1620 children with diarrhea, 2082 with fever, and 2134 with cough were
      included in the analyses. Multivariate logistic regression with a 95% confidence
      interval, adjusted odds-ratio, and a P < 0.05 were used to determine the
      independent effect of each variable. RESULTS: Household wealth-status, maternal
      and paternal education, and religion were found to be associated with the
      inequality in the use of child health services. Respondents from households with
      the richest, richer, and middle wealth status had higher odds of seeking medical
      treatment for childhood diarrhea, cough, and fever than that of the poorest ones.
      Maternal and paternal educational status was also associated with medical
      treatment seeking behavior for childhood diarrhea and fever, respectively.
      CONCLUSION: Household wealth and educational status of parents were possible
      determinant factors for the inequalities observed in health care seeking
      behavior. Policy interventions aimed at improving the appropriate medical
      treatment seeking behavior for common childhood illnesses are desirable.
      Practical economic policies aimed at moving those in the lower wealth quintile
      are essential to bridge the gap between the rich and the poor. Studies comprising
      qualitative and quantitative methods are recommended to further explore other
      determinants of health care utilization.

PMID- 28431504
TI  - Erratum to: RUNX1 induces DNA replication independent active DNA demethylation at
      SPI1 regulatory regions.

PMID- 28431503
TI  - Understanding the impact of symptoms on the burden of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on
      individuals with the disease, which can include a range of symptoms
      (breathlessness, cough, sputum production, wheeze, chest tightness) of varying
      severities. We present an overview of the biomedical literature describing
      reported relationships between COPD symptoms and disease burden in terms of
      quality of life, health status, daily activities, physical activity, sleep,
      comorbid anxiety, and depression, as well as risk of exacerbations and disease
      prognosis. In addition, the substantial variability of COPD symptoms encountered
      (morning, daytime, and nighttime) is addressed and their implications for disease
      burden considered. The findings from this narrative review, which mainly focuses
      on real-world and observational studies, demonstrate the impact of COPD symptoms
      on the burden of disease and that improved recognition and understanding of their
      impact is central to alleviating this burden.

PMID- 28431505
TI  - Using evaluability assessment to assess local community development health
      programmes: a Scottish case-study.
AB  - BACKGROUND: Evaluation of the potential effectiveness of a programme's objectives
      (health or otherwise) is important in demonstrating how programmes work. However,
      evaluations are expensive and can focus on unrealistic outcomes not grounded in
      strong theory, especially where there is pressure to show effectiveness. The aim
      of this research was to demonstrate that the evaluability assessment (a cost
      effective pre-evaluation tool that primarily gives quick, constructive feedback)
      can be used to help develop programme and outcome objectives to improve
      programmes while they run and to assist in producing more effective evaluations.
      This was done using the example of a community development programme aiming to
      improve health and reduce health inequalities in its target population. METHODS:
      The setting was Glasgow, Scotland, UK and focused on the Health Issues in the
      Community programme. Data were collected from documents and nine individual
      stakeholder interviews. Thematic analysis and a realist approach were used to
      analyse both datasets and, in conjunction with a workshop with stakeholders,
      produce a logic model of the programme theory and related evaluation options to
      explore further. RESULTS: Five main themes emerged from the analysis: History;
      Framework; Structure and Delivery of the Course; Theory of Action; and Barriers
      to Delivery and Successful Outcomes. These themes aided in drafting the logic
      model which revealed they key programme activities (e.g. facilitating group
      learning) and 23 potential outcomes. The majority of these outcomes (16) were
      deemed to be short-term outcomes (more easily measured within the timeframe of an
      individual being involved in the programme) e.g. increased self-esteem or
      awareness of individual/community health. The remaining 6 outcomes were deemed
      longer-term and included outcomes such as increased social capital and individual
      mental health and wellbeing. CONCLUSIONS: We have shown that the evaluability
      assessment tool can be applied to the evaluation of community health programmes,
      providing short- and long-term outcomes that could be evaluated to demonstrate
      effectiveness and avoid unnecessary or poorly designed full-scale evaluations.
      This type of pre-evaluation method is already a useful resource for national
      policy evaluations, but could be a valuable evaluation tool for other regional or
      community health programmes.

PMID- 28431506
TI  - Emotional and behavioural problems in Swedish preschool children rated by
      preschool teachers with the Strengths and Difficulties Questionnaire (SDQ).
AB  - BACKGROUND: There is a high risk that young children who show early signs of
      mental health problems develop symptoms in the same or overlapping areas some
      years later. The Strengths and Difficulties Questionnaire (SDQ) is widely used to
      screen externalizing and internalizing problems early in life. In Sweden 80-90%
      of all children aged 1-5 years go to preschool and preschool is thus an
      appropriate context for finding early signs of mental health problems among
      children. METHODS: This study is part of a longitudinal project too investigate
      the frequency of emotional and behavioural problems for children between 1 and 5
      years of age in Sweden. The SDQ including the impairment supplement questions
      were rated by preschool teachers too establish Swedish norms for SDQ in preschool
      children. RESULTS: The sample involved 815 children with a mean age of 42 months
      (SD = 16, range 13-71 months). 195 children were followed longitudinally for
      three years. There were significant differences between boys and girls on all
      subscales except for the Emotional subscale. The prevalence of behavioural
      problems was similar to other that in European countries, except for Prosocial
      behaviour, which was rated lower, and Conduct problems, rated higher. Swedish
      children were estimated to have more problems in the preschool setting, scored by
      preschool teachers. The development of behaviour over time differed for the
      different subscales of SDQ. CONCLUSIONS: The teacher version of the SDQ, for 2-4
      year-olds, can be used as a screening instrument to identify early signs of
      emotional distress/behavioural problems in young children. Preschool teachers
      seem to be able to identify children with problematic behaviour with the use of
      SDQ at an early age. The development of behaviour over time differs for the
      different subscales of SDQ. The Swedish norms for SDQ are to a large extent,
      similar to findings from other European countries.

PMID- 28431507
TI  - Antimicrobial prophylaxis outside the operating theatre, an audit in a university
      hospital.
AB  - BACKGROUND: The prophylactic use of antimicrobial agents to prevent infections in
      non-surgical situations has hardly been investigated. We investigate the extent,
      indications and appropriateness of antimicrobial prophylaxis given outside the
      operating room in a tertiary care hospital. METHODS: Four point-prevalence
      surveys were conducted in which all inpatients on that day were screened for the
      use of prophylactic antimicrobials: medical prophylaxis, prophylaxis around non
      surgical interventions and surgical prophylaxis given on the ward. The primary
      endpoint was the extent of prophylaxis relative to the total number of
      antimicrobial prescriptions. We also investigated per prescription the presence
      of a (local) protocol and adherence to these protocols. RESULTS: We registered in
      total 1020 antimicrobial prescriptions, of which 317 (31.1%) were given as
      prophylaxis. 827/1020 were antibiotic prescriptions. Of these antibiotic
      prescriptions, 17.0% was medical prophylaxis, 2.7% prophylaxis around non
      surgical interventions and 6.9% surgical prophylaxis administered on a ward. For
      medical antibiotic prophylaxis, a protocol was present in 125 of 141
      prescriptions (88.7%); the protocol was followed in 118 cases (94.4%). For
      prophylaxis around non-surgical interventions and surgical prophylaxis on the
      wards, protocol presence and adherence rates were 59.1% and 92.3%, and 73.3% and
      97.6% respectively. Of the 96 antiviral and 97 antifungal prescriptions, 42.7%
      and 57.8%, respectively, were medical prophylaxis, of which 95.1 and 96.3% were
      prescribed according to protocols respectively. CONCLUSIONS: Antimicrobial
      prophylaxis outside the operating theatre is responsible for a considerable part
      of total in-hospital antimicrobial use. For most prescriptions there was a
      protocol and adherence to the protocols was high. The main targets for
      improvement were prophylaxis around non-surgical interventions and surgical
      prophylaxis given on the ward.

PMID- 28431509
TI  - Regular recreational physical activity and risk of head and neck cancer.
AB  - BACKGROUND: Although substantial evidence supports a 20-30% risk reduction of
      colon cancer, breast cancer, and endometrial cancer by physical activity (PA),
      the evidence for head and neck cancer (HNC) is limited. Three published studies
      on the association between PA and HNC have generated inconsistent results. The
      current study examined the association between recreational PA (RPA) and HNC risk
      with a more detailed assessment on the intensity, frequency, duration, and total
      years of RPA. METHODS: Data on RPA were collected from 623 HNC cases and 731
      controls by in-person interview using a standardized questionnaire. The
      association between RPA and HNC risk was assessed using unconditional logistic
      regression, adjusted for sex, age, educational level, use of alcohol, betel quid,
      and cigarette, and consumption of vegetables and fruits. RESULTS: A significant
      inverse association between RPA and HNC risk was observed in a logistic
      regression model that adjusted for sex, age, and education (odds ratio (OR) =
      0.65, 95% confidence interval (CI): 0.51-0.82). However, after further adjustment
      for the use of alcohol, betel quid, and cigarette, and consumption of vegetables
      and fruits, RPA was no longer associated with HNC risk (OR =0.97, 95% CI: 0.73
      1.28). No significant inverse association between RPA and HNC risk was observed
      in the analysis stratified by HNC sites or by the use of alcohol, betel quid, or
      cigarette. CONCLUSION: Results from our study did not support an inverse
      association between RPA and HNC risk. The major focus of HNC prevention should be
      on cessation of cigarette smoking and betel chewing, reduction of alcohol
      drinking, and promotion of healthy diet that contains plenty of fruits and
      vegetables.

PMID- 28431508
TI  - Association between cardiopulmonary resuscitation duration and one-month
      neurological outcomes for out-of-hospital cardiac arrest: a prospective cohort
      study.
AB  - BACKGROUND: The duration of cardiopulmonary resuscitation (CPR) is an important
      factor associated with the outcomes for an out-of-hospital cardiac arrest.
      However, the appropriate CPR duration remains unclear considering pre- and in
      hospital settings. The present study aimed to evaluate the relationship between
      the CPR duration (including both the pre- and in-hospital duration) and
      neurologically favorable outcomes 1-month after cardiac arrest. METHODS: Data
      were utilized from a prospective multi-center cohort study of out-of-hospital
      cardiac arrest patients transported to 67 emergency hospitals between January
      2012 and March 2013 in the Kanto area of Japan. A total of 3,353 patients with
      out-of-hospital cardiac arrest (age >=18 years) who underwent CPR by emergency
      medical service personnel and achieved the return of spontaneous circulation in a
      pre- or in-hospital setting were analyzed. The primary outcome was a 1-month
      favorable neurological outcome. Logistic regression analysis was performed to
      estimate the influence of cardiopulmonary resuscitation duration. The CPR
      duration that achieved a cumulative proportion >99% of cases with a 1-month
      neurologically favorable outcome was determined. RESULTS: Of the 3,353 eligible
      cases, pre-hospital return of spontaneous circulation was obtained in 1,692 cases
      (50.5%). A total of 279 (8.3%) cases had a 1-month neurologically favorable
      outcome. The CPR duration was significantly and inversely associated with 1-month
      neurologically favorable outcomes with adjustment for pre- and in-hospital
      confounders (adjusted odds ratio: 0.911, per minute, 95% CI: 0.892-0.929, p <
      0.001). After 30 min of CPR, the probability of a 1-month neurologically
      favorable outcome decreased from 8.3 to 0.7%. At 45 min of CPR, the cumulative
      proportion for a 1-month neurologically favorable outcome reached >99%.
      CONCLUSIONS: The CPR duration was independently and inversely associated with 1
      month neurologically favorable outcomes after out-of-hospital cardiac arrest. The
      CPR duration required to achieve return of spontaneous circulation in >99% of out
      of-hospital cardiac arrest patients with a 1-month favorable neurological outcome
      was 45 min, considering both pre- and in-hospital settings.

PMID- 28431510
TI  - Delayed response to cold stress is characterized by successive metabolic shifts
      culminating in apple fruit peel necrosis.
AB  - BACKGROUND: Superficial scald is a physiological disorder of apple fruit
      characterized by sunken, necrotic lesions appearing after prolonged cold storage,
      although initial injury occurs much earlier in the storage period. To determine
      the degree to which the transition to cell death is an active process and
      specific metabolism involved, untargeted metabolic and transcriptomic profiling
      was used to follow metabolism of peel tissue over 180 d of cold storage. RESULTS:
      The metabolome and transcriptome of peel destined to develop scald began to
      diverge from peel where scald was controlled using antioxidant (diphenylamine;
      DPA) or rendered insensitive to ethylene using 1-methylcyclopropene (1-MCP)
      beginning between 30 and 60 days of storage. Overall metabolic and transcriptomic
      shifts, representing multiple pathways and processes, occurred alongside alpha
      farnesene oxidation and, later, methanol production alongside symptom
      development. CONCLUSIONS: Results indicate this form of peel necrosis is a
      product of an active metabolic transition involving multiple pathways triggered
      by chilling temperatures at cold storage inception rather than physical injury.
      Among multiple other pathways, enhanced methanol and methyl ester levels
      alongside upregulated pectin methylesterases are unique to peel that is
      developing scald symptoms similar to injury resulting from mechanical stress and
      herbivory in other plants.

PMID- 28431511
TI  - Validation of the short version of the 10/66 dementia diagnosis in multiethnic
      Asian older adults in Singapore.
AB  - BACKGROUND: To validate the short version of the 10/66 dementia diagnosis against
      the standard version of the 10/66 dementia diagnosis and clinical diagnosis and
      examine concurrent validity with the World Health Organisation Disability
      Assessment schedule and care needs in a multiethnic Asian older adult population
      in Singapore. METHODS: Data from the Well-being of the Singapore Elderly study, a
      nationally representative survey of the older Singapore Resident population aged
      60 years and above was used. The validity of the short version of the 10/66
      dementia diagnostic criteria derived from the Community Screening Instrument for
      Dementia, the modified Consortium to Establish a Registry of Alzheimer's Disease
      10-word list delayed recall and the EURO-D depression screen were examined
      against the standard version of the 10/66 dementia diagnosis and clinician
      diagnosis as a gold standard. Concurrent validity was tested by examining the
      relationships between the short version 10/66 dementia diagnosis, disability and
      care needs. RESULTS: A total of 2373 respondents who had completed data on the
      short version diagnosis were included in this study. The majority (82.63%) of
      respondents were of Chinese descent, 9.86% were Malays, 6.12% were of Indian
      descent and 1.39% belonged to other ethnic group. We found the short version
      10/66 dementia diagnosis showed almost perfect agreement with the standard
      version 10/66 dementia diagnosis (kappa = 0.90, AUC = 0.96) and substantial
      agreement with clinical diagnosis (kappa = 0.70, AUC = 0.87). The weighted
      prevalence of dementia in the population was slightly higher based on the short
      version diagnosis than the standard version diagnosis (10.74% vs. 10.04%). We
      also found that those with the short version 10/66 dementia were significantly
      associated with higher disability (beta = 28.90, 95% CI = 23.62, 9.62) and needed
      care occasionally (OR =35.21, 95% CI = 18.08, 68.59) or much of the time (OR =
      9.02, 95% CI = 5.21, 15.61). CONCLUSIONS: The study found that the short version
      10/66 dementia diagnosis has excellent validity to diagnose dementia in a
      multiethnic Asian population in Singapore. Further research is required to
      determine the usefulness of this diagnosis in clinical practice or institutional
      settings to aid early detection and intervention for dementia.

PMID- 28431512
TI  - Hemoglobin A1c and risk of left atrial thrombus and spontaneous echo contrast in
      non-valvular atrial fibrillation patients.
AB  - OBJECTIVES: To evaluate the relationship between hemoglobin A1c (HbA1c) and risk
      of left atrial thrombus/spontaneous echo contrast (LAT/SEC) in non-valvular
      atrial fibrillation (AF) patients. METHODS: In this retrospective study, 1158
      consecutive non-valvular AF patients undergoing transesophageal echocardiography
      prior to radiofrequency catheter ablation or electric cardioversion were
      enrolled. Baseline characteristics were collected and analyzed. RESULTS: There
      were 87 (7.5%) patients with LAT/SEC. The HbA1c levels in the patients with
      LAT/SEC were significantly higher than that in patients without LAT/SEC (6.13 +/-
      0.41 vs. 5.89 +/- 0.45 MUmol/L, P < 0.001). The optimal cut-off point for HbA1c
      predicting LAT/SEC was 6.1% determined by receiver-operating characteristic
      curve. The area under the curve is 0.788 (95% confidence interval: 0.764-0.812).
      HbA1c >=6.1% was an independent risk factor for LAT/SEC (odds ratio, 1.74; 95%
      confidence interval, 1.01-2.98; P = 0.045). CONCLUSIONS: Elevated HbA1c indicated
      a significantly increased risk for LAT/SEC in non-valvular AF patients. HbA1c
      might have significance in predicting the risk for prothrombotic state in non
      valvular AF patients.

PMID- 28431513
TI  - Functional characterization of cucumber (Cucumis sativus L.) Clade V MLO genes.
AB  - BACKGROUND: Powdery mildew (PM) causing fungi are well-known pathogens, infecting
      over 10.000 plant species, including the economically important crop cucumber
      (Cucumis sativus L.). Loss-of-function mutations in clade V MLO genes have
      previously been shown to lead to recessively inherited broad-spectrum resistance
      to PM in several species. In cucumber, one clade V MLO homolog (CsaMLO8) was
      previously identified as being a susceptibility factor to PM. Two other closely
      related homologs (CsaMLO1 and CsaMLO11) were found, but their function was not
      yet unravelled. METHODS: CsaMLO1 and CsaMLO11 were cloned from cucumber and
      overexpressed in a tomato mlo mutant. The transcript abundances of all three
      CsaMLO genes in different cucumber tissues were quantified using qRT-PCR and RNA
      seq, with and without inoculation with the cucumber PM fungus Podosphaera
      xanthii. Allelic variation of CsaMLO1 and CsaMLO11 was screened in silico in
      sequenced cucumber germplasm. RESULTS: Heterologous overexpression of all three
      CsaMLO genes in the tomato mlo mutant restored susceptibility to PM caused by
      Oidium neolycopersici, albeit to a different extent: whereas overexpression of
      CsaMLO1 or CsaMLO8 completely restored susceptibility, overexpression of CsaMLO11
      was only partially able to restore PM susceptibility. Furthermore, it was
      observed by qRT-PCR and RNA-seq that CsaMLO8 was significantly higher expressed
      in non-inoculated cucumber compared to the other two MLO genes. However,
      inoculation with P. xanthii led to upregulation of CsaMLO1, but not to
      upregulation of CsaMLO8 or CsaMLO11. CONCLUSIONS: Both CsaMLO1 and CsaMLO11 are
      functional susceptibility genes, although we conclude that based on the
      transcript abundance CsaMLO8 is probably the major clade V MLO gene in cucumber
      regarding providing susceptibility to PM. Potential loss-of-function mutations in
      CsaMLO1 and CsaMLO11 have not been identified. The generation and analysis of
      such mutants are interesting subjects for further investigation.

PMID- 28431514
TI  - Associations between matrix metalloproteinase gene polymorphisms and glaucoma
      susceptibility: a meta-analysis.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) polymorphisms have been implicated
      in the pathogenesis of glaucoma risk. However, the results were controversial. We
      performed a meta-analysis to evaluate the precise associations between MMPs
      polymorphisms and glaucoma risk. METHODS: Related studies were reviewed by
      searching electronic databases within four databases. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were calculated to assess the association between the
      most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication
      bias and sensitivity analysis were conducted to guarantee the statistical power.
      RESULTS: Overall, 11 selected articles involving 2,388 cases and 2,319 controls
      were included in this meta-analysis. Significant associations were only found
      between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67
      0.97, P = 0.02, I2 = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR
      = 0.71, 95%CI = 0.51-0.98, P = 0.04, I2 = 0%) and glaucoma risk in the general
      population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related
      to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00,
      P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I2 = 0%).
      CONCLUSIONS: Our meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism
      might be a protective factor against the development of glaucoma in Caucasian
      population.

PMID- 28431515
TI  - The effectiveness of creating an online life story book on persons with early
      dementia and their informal caregivers: a protocol of a randomized controlled
      trial.
AB  - BACKGROUND: Dementia has a high burden for patients, informal caregivers and
      society. Given changes in care systems, more persons with dementia will live
      longer at home. However, living at home (with dementia) with a good quality of
      life is not easy to achieve. Dementia is often accompanied by neuropsychiatric
      symptoms like apathy, agitation, depression, and anxiety, which have a negative
      impact on quality of life. Whereas cognitive deterioration can hardly be
      influenced, it is possible to reduce neuropsychiatric symptoms. As
      autobiographical memories remain intact for a relatively long time in dementia,
      reminiscence interventions can promote feelings of pleasure and trust. The Online
      Life Story Book (OLSB) allows to digitally share memories (stories, pictures,
      video or audio fragments). The main objective is to study the effects of the OLSB
      on neuropsychiatric symptoms. The study has four secondary objectives: 1) to
      study the effectiveness of the intervention on the burden and quality of life of
      the primary informal caregiver; 2) to provide a preliminary health-economic
      evaluation; 3) to study the (time to) nursing home admittance as a longer term
      effect; 4) to provide a process evaluation. METHODS AND DESIGN: A randomized
      controlled trial with individual randomization to one of two conditions is
      conducted: 1) intervention "Online Life Story Book"; 2) control condition (care
      as usual). Participants are persons with early dementia and their primary
      caregivers. In the intervention OLSB, a trained volunteer guides the participants
      through the process of putting together a timeline of their lives during 5
      meetings within a period of 8-10 weeks. To assess the effects of the intervention
      on the primary outcome, neuropsychiatric symptoms, the Neuropsychiatric Inventory
      (NPI) will be assessed at three time points: before the intervention (baseline,
      T0), 3 months (T1) and 6 months (T2) post baseline. DISCUSSION: When proven
      effective, the Online Life Story Book can be a valuable addition to the existing
      provision of care for persons with dementia and their informal caregivers. TRIAL
      REGISTRATION: This study has been approved by the Twente Medical Ethics Committee
      under the file number p16-04 (Dutch Trial Register: NTR5939 , date of
      registration: 14 March 2016).

PMID- 28431516
TI  - Evaluation of the impact of disease prevention measures: a methodological note on
      defining incidence rates.
AB  - BACKGROUND: In studies of recurrent events, it is common to consider a person who
      has suffered a disease episode and received curative treatment to be not at risk
      of suffering a new episode for a duration of time. It is a common practice to
      deduct this duration from the person's observation time in the statistical
      analysis of the incidence data. METHODS: We examined the concepts of incidence
      and protective efficacy from a real life point of view. We developed simple
      formulae to show the relationship between the incidence rate and protective
      efficacy between analyses with and without deducting the curative treatment time
      from the observation time. We used a malaria chemoprevention and a malaria
      vaccine study, both previously published, to illustrate the differences. RESULTS:
      Applying the formulae we derived to a range of disease incidence that covered the
      two case studies, we demonstrated the divergence of the two sets of estimates
      when incidence rate is approximately 1 per person-year or higher. In the malaria
      chemoprevention study, incidence was 5.40 per person-year after the deduction of
      curative treatment time from observation time but 4.48 per person-year without
      the deduction. The chemoprevention offered 56.6 and 50.7% protection calculated
      with and without the deduction, respectively. In the malaria vaccine study, where
      disease incidence was much lower than one, the results between the two ways of
      analysis were similar. For answering real life questions about disease burden in
      the population in a calendar year and the reduction that may be achieved if an
      intervention is implemented, the definition without deduction of curative
      treatment time should be used. CONCLUSIONS: The practice of deducting curative
      treatment time from observation time is not wrong, but it is not always the best
      approach. Investigators should consider the appropriateness of the two analytic
      procedures in relation to the specific research aims and the intended use of the
      results.

PMID- 28431517
TI  - Sharp bounds on sufficient-cause interactions under the assumption of no
      redundancy.
AB  - BACKGROUND: Sufficient-cause interaction is a type of interaction that has
      received much attention recently. The sufficient component cause model on which
      the sufficient-cause interaction is based is however a non-identifiable model.
      Estimating the interaction parameters from the model is mathematically
      impossible. METHODS: In this paper, I derive bounding formulae for sufficient
      cause interactions under the assumption of no redundancy. RESULTS: Two real data
      sets are used to demonstrate the method (R codes provided). The proposed bounds
      are sharp and sharper than previous bounds. CONCLUSIONS: Sufficient-cause
      interactions can be quantified by setting bounds on them.

PMID- 28431518
TI  - Is adjuvant chemotherapy necessary in pT1N1 gastric cancer?
AB  - BACKGROUND: Due to a lack of consensus on adjuvant treatments for pT1N1 gastric
      cancer, surgeons face a dilemma when deciding treatments for patients with pT1N1
      gastric cancer after gastrectomy. The objective of this study was to determine
      survival benefits of adjuvant chemotherapy and risk factors for tumor recurrence
      in gastric cancer patients with pT1N1. METHODS: Between 1996 and 2010, 510
      patients who underwent curative resection for pT1N1 gastric cancer at three
      institutes were divided into two groups: adjuvant chemotherapy group (N = 150)
      and surgery-only group (N = 360). Disease-free survival rates and risk factors
      for tumor recurrence were analyzed. RESULTS: During the median follow-up of 78
      months, 7.5% of patients experienced tumor recurrence (7.3% in adjuvant
      chemotherapy group and 7.5% in surgery-only group). The 5-year disease-free
      survival rate was 91.8% in the adjuvant chemotherapy group and 94.6% in the
      surgery-only group without significant difference between the two. In univariate
      analysis, older age (>65 years), male gender, body mass index <25 kg/m2, elevated
      gross type, and differentiated histology were associated with tumor recurrence.
      Multivariate analysis showed that advanced age and male gender were independent
      risk factors for tumor recurrence. In addition, adjuvant chemotherapy showed no
      benefitial effect on tumor recurrence in pT1N1 gastric cancer. CONCLUSIONS:
      Adjuvant chemotherapy did not show any oncologically benefitial effect on tumor
      recurrence, it might be unnecessary for pT1N1 gastric cancer after curative
      surgery.

PMID- 28431519
TI  - Semi-automatic synthesis and biodistribution of N-(2-18F-fluoropropionyl)
      bis(zinc (II)-dipicolylamine) (18F-FP-DPAZn2) for AD model imaging.
AB  - BACKGROUND: Phosphatidylserine (PS)-targeting positron emission tomography (PET)
      imaging with labeled small-molecule tracer is a crucial non-invasive molecule
      imaging method of apoptosis. In this study, semi-automatic radiosynthesis and
      biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc(II)-dipicolylamine) (18F-FP
      DPAZn2), as a potential small-molecule tracer for PET imaging of cell death in
      Alzheimer's disease (AD) model, were performed. METHODS: 18F-FP-DPAZn2 was
      synthesized on the modified PET-MF-2V-IT-I synthesizer. Biodistribution was
      determined in normal mice and PET images of AD model were obtained on a micro PET
      CT scanner. RESULTS: With the modified synthesizer, the total decay-corrected
      radiochemical yield of 18F-FP-DPAZn2 was 35 +/- 6% (n = 5) from 18F- within 105
      +/- 10 min. Biodistribution results showed that kidney has the highest uptake of
      18F-FP-DPAZn2. The uptake of radioactivity in brain kept at a relatively low
      level during the whole observed time. In vivo 18F-FP-DPAZn2 PET images
      demonstrated more accumulation of radioactivity in the brain of AD model mice
      than that in the brain of normal mice. CONCLUSIONS: The semi-automatic synthetic
      method provides a slightly higher radiochemical yield and shorter whole synthesis
      time of 18F-FP-DPAZn2 than the manual operation method. This improved method can
      give enough radioactivity and high radiochemical purity of 18F-FP-DPAZn2 for in
      vivo PET imaging. The results show that 18F-FP-DPAZn2 seems to be a potential
      cell death tracer for AD imaging.

PMID- 28431520
TI  - Infectious agents is a risk factor for myxomatous mitral valve degeneration: A
      case control study.
AB  - BACKGROUND: The etiology of myxomatous mitral valve degeneration (MVD) is not
      fully understood and may depend on time or environmental factors for which the
      interaction of infectious agents has not been documented. The purpose of the
      study is to analyze the effect of Mycoplasma pneumoniae (Mp), Chlamydophila
      pneumoniae (Cp) and Borrelia burgdorferi (Bb) on myxomatous mitral valve
      degeneration pathogenesis and establish whether increased in inflammation and
      collagen degradation in myxomatous mitral valve degeneration etiopathogenesis.
      METHODS: An immunohistochemical test was performed to detect the inflammatory
      cells (CD20, CD45, CD68) and Mp, Bb and MMP9 antigens in two groups. The in situ
      hybridization was performed to detect Chlamydophila pneumoniae and the bacteria
      study was performed using transmission electron microscopy. Group 1 (n = 20),
      surgical specimen composed by myxomatous mitral valve degeneration, and group 2
      (n = 20), autopsy specimen composed by normal mitral valve. The data were
      analyzed using SigmaStat version 20 (SPSS Inc., Chicago, IL, USA). The groups
      were compared using Student's t test, Mann-Whitney test. A correlation analysis
      was performed using Spearman's correlation test. P values lower than 0.05 were
      considered statistically significant. RESULTS: By immunohistochemistry, there was
      a higher inflammatory cells/mm2 for CD20 and CD45 in group 1, and CD68 in group
      2. Higher number of Mp and Cp antigens was observed in group 1 and more Bb
      antigens was detected in group 2. The group 1 exhibited a positive correlation
      between the Bb and MVD percentage, between CD45 and Mp, and between MMP9 with Mp.
      These correlations were not observed in the group 2. Electron microscopy revealed
      the presence of structures compatible with microorganisms that feature Borrelia
      and Mycoplasma characteristics. CONCLUSIONS: The presence of infectious agents,
      inflammatory cells and collagenases in mitral valves appear to contribute to the
      pathogenesis of MVD. Mycoplasma pneumoniae was strongly related with myxomatous
      mitral valve degeneration. Despite of low percentage of Borrelia burgdorferi in
      MD group, this agent was correlated with myxomatous degeneration and this may
      occour due synergistic actions between these infectious agents likely contribute
      to collagen degradation.

PMID- 28431521
TI  - A reference floral transcriptome of sexual and apomictic Paspalum notatum.
AB  - BACKGROUND: Paspalum notatum Flugge is a subtropical grass native to South
      America, which includes sexual diploid and apomictic polyploid biotypes. In the
      past decade, a number of apomixis-associated genes were discovered in this
      species through genetic mapping and differential expression surveys. However, the
      scarce information on Paspalum sequences available in public databanks limited
      annotations and functional predictions for these candidates. RESULTS: We used a
      long-read 454/Roche FLX+ sequencing strategy to produce robust reference
      transcriptome datasets from florets of sexual and apomictic Paspalum notatum
      genotypes and delivered a list of transcripts showing differential representation
      in both reproductive types. Raw data originated from floral samples collected
      from premeiosis to anthesis was assembled in three libraries: i) sexual (SEX),
      ii) apomictic (APO) and iii) global (SEX + APO). A group of physically-supported
      Paspalum mRNA and EST sequences matched with high level of confidence to both
      sexual and apomictic libraries. A preliminary trial allowed discovery of the
      whole set of putative alleles/paralogs corresponding to 23 previously identified
      apomixis-associated candidate genes. Moreover, a list of 3,732 transcripts and
      several co-expression and protein -protein interaction networks associated with
      apomixis were identified. CONCLUSIONS: The use of the 454/Roche FLX+
      transcriptome database will allow the detailed characterization of floral
      alleles/paralogs of apomixis candidate genes identified in prior and future work.
      Moreover, it was used to reveal additional candidate genes differentially
      represented in apomictic and sexual flowers. Gene ontology (GO) analyses of this
      set of transcripts indicated that the main molecular pathways altered in the
      apomictic genotype correspond to specific biological processes, like biotic and
      abiotic stress responses, growth, development, cell death and senescence. This
      data collection will be of interest to the plant reproduction research community
      and, particularly, to Paspalum breeding projects.

PMID- 28431523
TI  - The utility of electron microscopy in detecting asbestos fibers and particles in
      BALF in diffuse lung diseases.
AB  - BACKGROUND: In patients with diffuse lung diseases, differentiating occupational
      lung diseases from other diseases is clinically important. However, the value of
      assessing asbestos and particles in bronchoalveolar lavage fluid (BALF) in
      diffuse lung diseases by electron microscopy (EM) remains unclear. We evaluated
      the utility of EM in detecting asbestos fibers and particles in patients with
      diffuse lung diseases. METHODS: The BALF specimens of 107 patients with diffuse
      lung diseases were evaluated. First, detection of asbestos by EM and light
      microscopy (LM) were compared. Second, the detection of asbestos using surgically
      obtained lung tissues of 8 of 107 patients were compared with the results of EM
      and LM in BALF. Third, we compared the results of mineralogical components of
      particles in patients with (n = 48) and without (n = 59) a history of
      occupational exposure to inorganic dust. RESULTS: BALF asbestos were detected in
      11 of 48 patients with a history of occupational exposure by EM; whereas asbestos
      as asbestos bodies (ABs) were detected in BALF in 4 of these 11 patients by LM.
      Eight of 107 patients in whom lung tissue samples were surgically obtained, EM
      detected BALF asbestos at a level of >1,000 fibers/ml in all three patients who
      had ABs in lung tissue samples by LM at a level of >1,000 fibers/g. The BALF
      asbestos concentration by EM and in lung tissue by LM were positively correlated.
      The particle fractions of iron and phosphorus were increased in patients with a
      history of occupational exposure and both correlated with a history of
      occupational exposure by a multiple regression analysis. CONCLUSIONS: EM using
      BALF seemed to be superior to LM using BALF and displayed a similar sensitivity
      to LM using surgically-obtained lung tissue samples in the detection of asbestos.
      Our results also suggest that detection of elements, such as iron and phosphorus
      in particles, is useful for evaluating occupational exposure. We conclude that
      the detection of asbestos and iron and phosphorus in particles in BALF by EM is
      very useful for the evaluation of occupational exposure.

PMID- 28431522
TI  - Comparative proteomic analysis of Neisseria meningitidis wildtype and dprA null
      mutant strains links DNA processing to pilus biogenesis.
AB  - BACKGROUND: DNA processing chain A (DprA) is a DNA binding protein which is
      ubiquitous in bacteria, and is required for DNA transformation to various extents
      among bacterial species. However, the interaction of DprA with competence and
      recombination proteins is poorly understood. Therefore, the proteomes of whole
      Neisseria meningitidis (Nm) wildtype and dprA mutant cells were compared. Such a
      comparative proteomic analysis increases our understanding of the interactions of
      DprA with other Nm components and may elucidate its potential role beyond DNA
      processing in transformation. RESULTS: Using label-free quantitative proteomics,
      a total of 1057 unique Nm proteins were identified, out of which 100 were
      quantified as differentially abundant (P <= 0.05 and fold change >= |2|) in the
      dprA null mutant. Proteins involved in homologous recombination (RecA, UvrD and
      HolA), pilus biogenesis (PilG, PilT1, PilT2, PilM, PilO, PilQ, PilF and PilE),
      cell division, including core energy metabolism, and response to oxidative stress
      were downregulated in the Nm dprA null mutant. The mass spectrometry data are
      available via ProteomeXchange with identifier PXD006121. Immunoblotting and co
      immunoprecipitation were employed to validate the association of DprA with PilG.
      The analysis revealed reduced amounts of PilG in the dprA null mutant and reduced
      amounts of DprA in the Nm pilG null mutant. Moreover, a number of pilus
      biogenesis proteins were shown to interact with DprA and /or PilG. CONCLUSIONS:
      DprA interacts with proteins essential for Nm DNA recombination in
      transformation, pilus biogenesis, and other functions associated with the inner
      membrane. Inverse downregulation of Nm DprA and PilG expression in the
      corresponding mutants indicates a link between DNA processing and pilus
      biogenesis.

PMID- 28431524
TI  - Biosecurity survey in relation to the risk of HPAI outbreaks in backyard poultry
      holdings in Thimphu city area, Bhutan.
AB  - BACKGROUND: A questionnaire survey was conducted to assess the biosecurity and
      other practices of backyard poultry holdings and knowledge and practices of
      poultry keepers following an outbreak of highly pathogenic avian influenza (H5N1)
      virus in poultry in Thimphu city area, Bhutan. RESULTS: The study identified 62
      backyard poultry holdings in 12 settlement areas, and the owners were
      subsequently interviewed. The birds are kept in a low-input low-output system,
      fed locally available scavenging feed base, and supplemented with food scraps and
      some grain. Although the birds are housed at night in a small coop to protect
      them against theft and predators, they are let loose during the day to scavenge
      in the homestead surroundings. This invariably results in mixing with other
      poultry birds within the settlement and wild birds, creating favorable conditions
      for disease spread within and between flocks. Moreover, the poultry keepers have
      a low level of knowledge and awareness related to the importance of biosecurity
      measures, as well as veterinary care of the birds and reporting systems. Of
      particular concern is that sick birds within backyard holdings may not be
      detected rapidly, resulting in silent spread of disease and increased risk of
      humans contacting the virus (e.g. HPAI) from infected poultry. Nevertheless, all
      the respondents have indicated that they know and practice hand washing using
      soap and water after handling poultry and poultry products, but rarely use face
      masks and hand gloves while handling poultry or cleaning poultry house.
      CONCLUSIONS: This study highlights the importance of educating poultry keepers to
      improve the housing and management systems of poultry farming within the backyard
      holdings in the Thimphu city area in order to prevent future disease outbreaks.

PMID- 28431525
TI  - Membrane-enriched proteome changes and prion protein expression during neural
      differentiation and in neuroblastoma cells.
AB  - BACKGROUND: The function of the prion protein, involved in the so-called prion
      diseases, remains a subject of intense debate and the possibility that it works
      as a pleiotropic protein through the interaction with multiple membrane proteins
      is somehow supported by recent reports. Therefore, the use of proteomic and
      bioinformatics combined to uncover cellular processes occurring together with
      changes in the expression of the prion protein may provide further insight into
      the putative pleiotropic role of the prion protein. RESULTS: This study assessed
      the membrane-enriched proteome changes accompanying alterations in the expression
      of the prion protein. A 2D-DIGE approach was applied to two cell lines after
      prefractionation towards the membrane protein subset: an embryonic stem cell line
      and the PK1 subline of neuroblastoma cells which efficiently propagates prion
      infection. Several proteins were differentially abundant with the increased
      expression of the prion protein during neural differentiation of embryonic stem
      cells and with the knockdown of the prion protein in PK1 cells. The identity of
      around 20% of the differentially abundant proteins was obtained by tandem MS. The
      catalytic subunit A of succinate dehydrogenase, a key enzyme for the aerobic
      energy metabolism and redox homeostasis, showed a similar abundance trend as the
      prion protein in both proteomic experiments. A gene ontology analysis revealed
      "myelin sheath", "organelle membrane" and "focal adhesion" associated proteins as
      the main cellular components, and "protein folding" and "ATPase activity" as the
      biological processes enriched in the first set of differentially abundant
      proteins. The known interactome of these differentially abundant proteins was
      customized to reveal four interactors with the prion protein, including two heat
      shock proteins and a protein disulfide isomerase. CONCLUSIONS: Overall, our study
      shows that expression of the prion protein occurs concomitantly with changes in
      chaperone activity and cell-redox homeostasis, emphasizing the functional link
      between these cellular processes and the prion protein.

PMID- 28431526
TI  - Recognition of depression by primary care clinicians in rural Ethiopia.
AB  - BACKGROUND: Depression is a common health condition affecting up to a third of
      patients attending primary care, where most of the care for people with
      depression is provided. Adequate recognition of depression is the critical step
      in the path to effective care, particularly in low income countries. As part of
      the Programme for Improving Mental healthcare (PRIME), a project supporting the
      implementation of integrated mental healthcare in primary care, we evaluated the
      level of recognition of depression by clinicians working in primary care in rural
      Ethiopia prior to in service training. We hypothesised that the detection rate of
      depression will be under 10% and that detection would be affected by gender,
      education and severity of depression. METHODS: Cross-sectional survey in eight
      health centres serving a population of over 160,000 people. A validated version
      of the 9-item patient health questionnaire (PHQ-9) was administered as an
      indicator of probable depression. In addition, primary care clinicians completed
      a clinician encounter form. Participants were consecutive primary care attendees
      aged 18 years and above. RESULTS: A total of 1014 participants were assessed.
      Primary care clinicians diagnosed 13 attendees (1.3%) with depression. The PHQ9
      prevalence of depression at a cut-off score of ten was 11.5% (n = 117), of whom
      5% (n = 6/117) had received a diagnosis of depression by primary care clinicians.
      Attendees with higher PHQ scores and suicidality were significantly more likely
      to receive a diagnosis of depression by clinicians. Women (n = 9/13) and
      participants with higher educational attainment were more likely to be diagnosed
      with depression, albeit non-significantly. All cases diagnosed with depression by
      the clinicians had presented with psychological symptoms. CONCLUSION: Although
      not based on a gold standard diagnosis, over 98% of cases with PHQ-9 depression
      were undetected. Failure of recognition of depression may pose a serious threat
      to the scale up of mental healthcare in low income countries. Addressing this
      threat should be an urgent priority, and requires a better understanding of the
      nature of depression and its presentation in rural low-income primary care
      settings.

PMID- 28431527
TI  - Evaluation of the correlation of vasculogenic mimicry, ALDH1, KAI1 and
      microvessel density in the prediction of metastasis and prognosis in colorectal
      carcinoma.
AB  - BACKGROUND: Metastasis and recurrence are the most common reasons for treatment
      failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply
      formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1
      (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor
      metastasis) are all valuable factors for metastasis and prognosis in diverse
      human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel
      density (MVD) in CRC is unclear. In this study, we analyzed the correlations
      among VM, ALDH1, KAI1 and MVD, as well as their respective correlations with
      clinicopathological parameters and survival in CRC. METHODS: The level of VM,
      ALDH1, KAI1 and MVD in 204 whole tissue samples of CRC were examined by
      immunhistochemistry. Clinical data was also collected. RESULTS: Levels of VM,
      ALDH1 and MVD were significantly higher, and levels of KAI1 significantly lower,
      in CRC tissues than in normal colorectal tissues. Levels of VM, ALDH1 and MVD
      were positively associated with invasion of depth, lymph node metastasis (LNM),
      distant metastasis and tumor-node-metastasis (TNM) stages, and negatively with
      patients' overall survival (OS). Levels of KAI1 was negatively correlated with
      invasion of depth, LNM, distant metastasis and TNM stages, and the KAI1 positive
      expression subgroup had significantly longer OS than did the KAI1- subgroup. In
      multivariate analysis, high levels of VM, ALDH1 and KAI1, as well as TNM stages
      were independently correlated with lower OS in patients with CRC. CONCLUSIONS:
      VM, MVD and the expression of ALDH1 and KAI1 may represent promising metastatic
      and prognostic biomarkers, as well as potential therapeutic targets for CRC.

PMID- 28431528
TI  - Diagnostic performance of the urinary canine calgranulins in dogs with lower
      urinary or urogenital tract carcinoma.
AB  - BACKGROUND: Onset of canine transitional cell carcinoma (TCC) and prostatic
      carcinoma (PCA) is usually insidious with dogs presenting at an advanced stage of
      the disease. A biomarker that can facilitate early detection of TCC/PCA and
      improve patient survival would be useful. S100A8/A9 (calgranulin A/B or
      calprotectin) and S100A12 (calgranulin C) are expressed by cells of the innate
      immune system and are associated with several inflammatory disorders. S100A8/A9
      is also expressed by epithelial cells after malignant transformation and is
      involved in the regulation of cell proliferation and metastasis. S100A8/A9 is up
      regulated in human PCA and TCC, whereas the results for S100A12 have been
      ambiguous. Also, the urine S100A8/A9-to-S100A12 ratio (uCalR) may have potential
      as a marker for canine TCC/PCA. Aim of the study was to evaluate the diagnostic
      accuracy of the urinary S100/calgranulins to detect TCC/PCA in dogs by using data
      and urine samples from 164 dogs with TCC/PCA, non-neoplastic urinary tract
      disease, other neoplasms, or urinary tract infections, and 75 healthy controls
      (nested case-control study). Urine S100A8/A9 and S100A12 (measured by species
      specific radioimmunoassays and normalized against urine specific gravity
      [S100A8/A9USG; S100A12USG], urine creatinine concentration, and urine protein
      concentration and the uCalR were compared among the groups of dogs. RESULTS:
      S100A8/A9USG had the highest sensitivity (96%) and specificity (66%) to detect
      TCC/PCA, with specificity reaching 75% after excluding dogs with a urinary tract
      infection. The uCalR best distinguished dogs with TCC/PCA from dogs with a
      urinary tract infection (sensitivity: 91%, specificity: 60%). Using a
      S100A8/A9USG >= 109.9 to screen dogs >=6 years of age for TCC/PCA yielded a
      negative predictive value of 100%. CONCLUSIONS: S100A8/A9USG and uCalR may have
      utility for diagnosing TCC/PCA in dogs, and S100A8/A9USG may be a good screening
      test for canine TCC/PCA.

PMID- 28431529
TI  - HirBin: high-resolution identification of differentially abundant functions in
      metagenomes.
AB  - BACKGROUND: Gene-centric analysis of metagenomics data provides information about
      the biochemical functions present in a microbiome under a certain condition. The
      ability to identify significant differences in functions between metagenomes is
      dependent on accurate classification and quantification of the sequence reads
      (binning). However, biological effects acting on specific functions may be
      overlooked if the classes are too general. METHODS: Here we introduce High
      Resolution Binning (HirBin), a new method for gene-centric analysis of
      metagenomes. HirBin combines supervised annotation with unsupervised clustering
      to bin sequence reads at a higher resolution. The supervised annotation is
      performed by matching sequence fragments to genes using well-established protein
      domains, such as TIGRFAM, PFAM or COGs, followed by unsupervised clustering where
      each functional domain is further divided into sub-bins based on sequence
      similarity. Finally, differential abundance of the sub-bins is statistically
      assessed. RESULTS:  We show that HirBin is able to identify biological effects
      that are only present at more specific functional levels. Furthermore we show
      that changes affecting more specific functional levels are often diluted at the
      more general level and therefore overlooked when analyzed using standard binning
      approaches. CONCLUSIONS: HirBin improves the resolution of the gene-centric
      analysis of metagenomes and facilitates the biological interpretation of the
      results. HirBin is implemented as a Python package and is freely available for
      download at http://bioinformatics.math.chalmers.se/hirbin .

PMID- 28431530
TI  - Are there too many screw holes in plates for fracture fixation?
AB  - BACKGROUND: Implant breakage after the fixation of traumatic fractures is rare;
      however, when it occurs, it is debilitating for the patients and a challenge for
      surgeons. The purpose of this study was to analyze and identify the independent
      risk factors for implant breakage of traumatic fractures treated with plate
      osteosynthesis. METHODS: We reviewed the medical records of patients with a
      fracture to any part of their four extremities, clavicle, hand or foot, who
      underwent surgical plate osteosynthesis from January 2005 to January 2015, and
      who sustained a subsequent implant breakage. Kaplan-Meier univariate and
      multivariate Cox regressions were performed to identify independent associations
      of potential risk factors for implant breakage in this cohort. RESULTS: We
      identified 168 patients who underwent plate osteosynthesis surgery and had
      subsequent internal fixator breakage. The mean patient age was 40.63 +/- 16.71
      years (range, 3 to 78 years), with 72.0% (121) males and 28.0% (47) females. The
      average time between surgery and implant breakage was 12.85 +/- 12.42 months
      (range, 1 to 60 months). In the final regression model, we show that inserting
      screws close to the fracture line is an independent predictive risk factor for
      implant breakage (HR, 2.165, 95%CI, 1.227 to 3.822; P = 0.008). CONCLUSIONS: We
      found that inserting screws close to the fracture line is related to an increased
      risk of internal fixator breakage in patients treated with plate osteosynthesis
      after fracture. Plates with additional holes likely lead to an increased risk of
      implant breakage, presumably because surgeons cannot resist inserting extra
      screws into the holes adjacent to the fracture line, which reduces the stiffness
      of the plate. We have addressed this problem by designing a plate without holes
      adjacent to the fracture line.

PMID- 28431531
TI  - Short-term surgical outcomes of laparoscopy-assisted versus totally laparoscopic
      Billroth-II gastrectomy for gastric cancer: a matched-cohort study.
AB  - BACKGROUND: To evaluate feasibility and benefits of intracorporeal anastomosis,
      we compared short-term surgical outcomes between laparoscopy-assisted distal
      gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) with
      Billroth-II (B-II) anastomosis for gastric cancer. METHODS: Sixty patients
      underwent attempted B-II TLDG from 2011 through 2013. Patients who underwent B-II
      LADG prior to 2011 were matched to TLDG cases for demographics, comorbidities,
      tumor characteristics, and TNM stage. Perioperative and short-term surgical
      outcomes were compared between the two groups. RESULTS: Clinicopathological
      characteristics of both groups were comparable. The B-II TLDG group had a shorter
      hospital stay (9.4 vs. 12.0 days, P = 0.038) and average incision size was
      smaller (3.5 vs. 5.4 cm, P = 0.030) than in the B-II LADG group. Anastomotic
      leakage was not recorded in either group, and there were no differences in the
      rates of perioperative complications and in inflammatory parameters between the
      two groups. CONCLUSIONS: This study suggests that B-II TLDG is feasible, compared
      to B-II LADG, and that it has several advantages over LADG, including a smaller
      incision, a shorter hospital stay, and more convenience during surgery. However,
      prospective randomized controlled studies are still needed to confirm that B-II
      TLDG can be used as a standard procedure for LDG.

PMID- 28431532
TI  - Residents' satisfaction with primary medical and health services in Western
      China.
AB  - BACKGROUND: Currently, China is in the process of medical and health care reform,
      and the establishment of primary medical and health services covering urban and
      rural residents is an important aspect of this process. Studying the satisfaction
      of residents of underdeveloped areas with their primary medical and health
      services and identifying the factors that can increase the satisfaction of
      different groups may improve patient compliance and ultimately improve health.
      Moreover, such research may provide a reference for the development of medical
      and health undertakings in similarly underdeveloped areas. METHODS: A face-to
      face survey was conducted on a stratified random sample of 2200 residents in
      Gansu by using structured questionnaires. Demographic characteristics were
      collated, and questionnaires were factor-analysed and weighted using SPSS
      software to obtain scores for each factor, as well as total satisfaction scores.
      The characteristics of poorly satisfied populations were determined by a multiple
      linear regression analysis using SAS software. A cluster analysis was performed
      using SAS software for classification and a separate discussion of populations.
      RESULTS: The hypertension self-awareness rate (11.29%) of the sampled population
      was lower than the average hypertension prevalence (23.85%), as recorded in the
      2014 Health Statistical Yearbook of the region. The disease knowledge awareness
      factor was the lowest factor (2.857), whereas the policy awareness factor was the
      highest factor (4.772). The overall satisfaction was moderate (3.898). The
      multivariate linear regression model was significant (p <0.05). The regression
      coefficients were -0.041 for minors; 0.065 for unemployed people; and 0.094 for
      people with an elementary school educational level, a value lower than that of
      other population groups. A cluster analysis was used to divide the respondents
      into five groups. The overall satisfaction was lowest in the second population
      group (rural, middle-aged)(Fz = 3.64) and was highest in the fourth population
      group(minors) (Fz = 4.13). Different population groups showed different
      satisfaction rates in F1 to F6. CONCLUSION: Hypertensive patients had low self
      awareness, and residents had a poor grasp of disease and limited health
      knowledge. Their overall satisfaction was moderate. Residents expressed
      comparatively high satisfaction with the current policy. Minors, adults with low
      level of education, unemployed people and other vulnerable groups expressed low
      overall satisfaction. The degree of satisfaction varied greatly among the
      different groups. Targeted medical and health practices should be implemented for
      different groups; additionally, the public health practice should be
      strengthened.

PMID- 28431533
TI  - Effect of a 16-week Bikram yoga program on heart rate variability and associated
      cardiovascular disease risk factors in stressed and sedentary adults: A
      randomized controlled trial.
AB  - BACKGROUND: Chronic activation of the stress-response can contribute to
      cardiovascular disease risk, particularly in sedentary individuals. This study
      investigated the effect of a Bikram yoga intervention on the high frequency power
      component of heart rate variability (HRV) and associated cardiovascular disease
      (CVD) risk factors (i.e. additional domains of HRV, hemodynamic, hematologic,
      anthropometric and body composition outcome measures) in stressed and sedentary
      adults. METHODS: Eligible adults were randomized to an experimental group (n =
      29) or a no treatment control group (n = 34). Experimental group participants
      were instructed to attend three to five supervised Bikram yoga classes per week
      for 16 weeks at local studios. Outcome measures were assessed at baseline (week
      0) and completion (week 17). RESULTS: Sixty-three adults (37.2 +/- 10.8 years,
      79% women) were included in the intention-to-treat analysis. The experimental
      group attended 27 +/- 18 classes. Analyses of covariance revealed no significant
      change in the high-frequency component of HRV (p = 0.912, partial eta 2 = 0.000)
      or in any secondary outcome measure between groups over time. However, regression
      analyses revealed that higher attendance in the experimental group was associated
      with significant reductions in diastolic blood pressure (p = 0.039; partial eta 2
      = 0.154), body fat percentage (p = 0.001, partial eta 2 = 0.379), fat mass (p =
      0.003, partial eta 2 = 0.294) and body mass index (p = 0.05, partial eta 2 =
      0.139). CONCLUSIONS: A 16-week Bikram yoga program did not increase the high
      frequency power component of HRV or any other CVD risk factors investigated. As
      revealed by post hoc analyses, low adherence likely contributed to the null
      effects. Future studies are required to address barriers to adherence to better
      elucidate the dose-response effects of Bikram yoga practice as a medium to lower
      stress-related CVD risk. TRIAL REGISTRATION: Retrospectively registered with
      Australia New Zealand Clinical Trials Registry ACTRN12616000867493 . Registered
      04 July 2016.

PMID- 28431534
TI  - The effects of Spirulina Platensis on anthropometric indices, appetite, lipid
      profile and serum vascular endothelial growth factor (VEGF) in obese individuals:
      a randomized double blinded placebo controlled trial.
AB  - BACKGROUND: In recent years, a great attention has been focused on Spirulina
      platensis as a source of potential valuable nutrients for prevention and
      treatment of chronic diseases. The objectives of the current study were to
      determine the effects of Spirulina platensis on anthropometric parameters, serum
      lipids, appetite and serum Vascular Endothelial Growth Factor (VEGF) in obese
      individuals. METHODS: In the current study sixty four obese individuals aged 20
      50 years were enrolled and randomly allocated into two groups of intervention and
      placebo. Intervention group (n = 29) received each 500 mg of the Spirulina
      platensis a twice-daily dosage while the control group (n = 27) received two
      pills daily starch for 12 weeks. Anthropometric parameters and serum VEGF and
      lipid profile were measured in fasting blood samples at the beginning and end of
      the study period. Dietary intakes were assessed by a 24-h recall method and
      appetite was measured using standard visual analogue scale (VAS). RESULTS: Body
      weight and body mass index (BMI) were decreased in intervention and placebo
      treated groups although the mean reduction in Spirulina platensis-treated group
      was significantly higher (P < 0.05). Serum total cholesterol (TC) significantly
      reduced in intervention group (P < 0.05). Also, treatment with Spirulina
      platensis significantly reduced appetite (P = 0.008). Mean serum VEGF, low
      density lipoprotein-cholesterol, and triglycerides did not change significantly
      after intervention. Serum high density lipoprotein-cholesterol concentrations
      (HDL-c) significantly increased in both groups while no difference in mean
      difference of this change has been observed. CONCLUSION: Spirulina
      supplementation at a dose of 1 g/d for 12 weeks is effective in modulating body
      weight and appetite and partly modifies serum lipids. This can further confirm
      the efficacy of this herbal supplement in control and prevention of obesity and
      obesity- related disorders. TRIAL REGISTRATION: Iranian registry of clinical
      trials (IRCT registration number: IRCT2015071219082N7 ; Date registered:
      September 12, 2015).

PMID- 28431535
TI  - Ion- and water-binding sites inside an occluded hourglass pore of a trimeric
      intracellular cation (TRIC) channel.
AB  - BACKGROUND: Trimeric intracellular cation (TRIC) channels are crucial for Ca2+
      handling in eukaryotes and are involved in K+ uptake in prokaryotes. Recent
      studies on the representative members of eukaryotic and prokaryotic TRIC channels
      demonstrated that they form homotrimeric units with the ion-conducting pores
      contained within each individual monomer. RESULTS: Here we report detailed
      insights into the ion- and water-binding sites inside the pore of a TRIC channel
      from Sulfolobus solfataricus (SsTRIC). Like the mammalian TRIC channels, SsTRIC
      is permeable to both K+ and Na+ with a slight preference for K+, and is nearly
      impermeable to Ca2+, Mg2+, or Cl-. In the 2.2-A resolution K+-bound structure of
      SsTRIC, ion/water densities have been well resolved inside the pore. At the
      central region, a filter-like structure is shaped by the kinks on the second and
      fifth transmembrane helices and two nearby phenylalanine residues. Below the
      filter, the cytoplasmic vestibule is occluded by a plug-like motif attached to an
      array of pore-lining charged residues. CONCLUSIONS: The asymmetric filter-like
      structure at the pore center of SsTRIC might serve as the basis for the channel
      to bind and select monovalent cations. A Velcro-like plug-pore interacting model
      has been proposed and suggests a unified framework accounting for the gating
      mechanisms of prokaryotic and eukaryotic TRIC channels.

PMID- 28431536
TI  - 'Popping nana back into bed' - a qualitative exploration of paramedic decision
      making when caring for older people who have fallen.
AB  - BACKGROUND: Older fallers constitute a large proportion of ambulance work, and as
      many as 25% are not transported to hospital following paramedic assessment. The
      objective of this study was to explore the decision making process used by
      paramedics when caring for older fallers. METHODS: A qualitative study was
      conducted using constructivist grounded theory methodology. Purposive sampling
      was used to recruit paramedics to participate in semi-structured interviews and
      focus groups. Data analysis commenced with line-by-line coding, developing into
      formation of theoretical categories. Theoretical sampling was then used to
      clarify emerging theoretical concepts, with data collection and analysis
      continuing until theoretical saturation was achieved. RESULTS: A total of 33
      paramedics participated in 13 interviews and 4 focus groups. When caring for
      older fallers, paramedic decision making is profoundly affected by 'role
      perception', in which the individual paramedic's perception of what the role of a
      paramedic is determines the nature of the decision making process. Transport
      decisions are heavily influenced by a sense of 'personal protection', or their
      confidence in the ambulance service supporting their decisions. 'Education and
      training' impacts on decision making capacity, and the nature of that training
      subliminally contributes to role perception. Role perception influences the sense
      of legitimacy a paramedic attaches to cases involving older fallers, impacting on
      patient assessment routines and the quality of subsequent decisions. CONCLUSIONS:
      Paramedic decision making processes when caring for older people who have fallen
      appear to be strongly influenced by their perception of what their role should
      be, and the perceived legitimacy of incidents involving older fallers as
      constituting 'real' paramedic work.

PMID- 28431537
TI  - The role of flower pollen extract in managing patients affected by chronic
      prostatitis/chronic pelvic pain syndrome: a comprehensive analysis of all
      published clinical trials.
AB  - BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still a
      challenge to manage for all physicians. We feel that a summary of the current
      literature and a systematic review to evaluate the therapeutic efficacy of flower
      pollen extract would be helpful for physicians who are considering a
      phytotherapeutic approach to treating patients with CP/CPPS. METHODS: A
      comprehensive search of the PubMed and Embase databases up to June 2016 was
      performed. This comprehensive analysis included both pre-clinical and clinical
      trials on the role of flower pollen extract in CP/CPPS patients. Moreover, a meta
      analysis of available randomized controlled trials (RCTs) was performed. The NIH
      Chronic Prostatitis Symptom Index (NIH-CPSI) and Quality of Life related
      questionnaires (QoL) were the most commonly used tools to evaluate the
      therapeutic efficacy of pollen extract. RESULTS: Pre-clinical studies
      demonstrated the anti-inflammatory and anti-proliferative role of pollen extract.
      6 clinical, non-controlled studies including 206 patients, and 4 RCTs including
      384 patients were conducted. The mean response rate in non-controlled studies was
      83.6% (62.2%-96.0%). The meta-analysis revealed that flower pollen extract could
      significantly improve patients' quality of life [OR 0.52 (0.34-.0.81); p = 0.02].
      No significant adverse events were reported. CONCLUSION: Most of these studies
      presented encouraging results in terms of variations in NIH-CPSI and QoL scores.
      These studies suggest that the use of flower pollen extract for the management of
      CP/CPPS patients is beneficial. Future publications of robust evidence from
      additional RCTs and longer-term follow-up would provide more support encouraging
      the use of flower pollen extracts for CP/CPPS patients.

PMID- 28431538
TI  - A prospective and randomized comparison of rigid ureteroscopic to flexible
      cystoscopic retrieval of ureteral stents.
AB  - BACKGROUND: Flexible cystoscopy has become an accepted alternative for stent
      retrieval. However, it is associated with higher cost. Some reports have
      described experiences of using rigid ureteroscope to retrieve ureteral stents. We
      compared rigid ureteroscopic to flexible cystoscopic retrieval of ureteral stents
      in a prospective and randomized clinical trial. METHODS: Three hundred patients
      treated with ureteral stents between July 2012 and July 2013 were accrued in this
      study. These patients were divided into two groups using the random number table
      method. Group A, with 162 patients, had stents removed with a flexible cystoscope
      and Group B, with 138 patients, had stents removed with a rigid ureteroscope. All
      procedures were performed under topical anesthesia by the same urologist.
      Patients in each group were compared in terms of preoperative, perioperative, and
      postoperative data. Postoperative data were collected using telephone interview
      on the postoperative day two. The postoperative questionnaire used included three
      items: hematuria, irritable bladder symptoms, and pain scores. RESULTS: All the
      stents were retrieved successfully. No statistical differences were noted between
      the two groups in terms of gender, age, laterality and duration of the stents,
      operative time, postoperative hematuria, irritable bladder symptoms, and pain
      scores. The per-use cost of instrument was much higher for the flexible
      cystoscopic group, RMB 723.1 versus 214.3 (USD 107.9 versus 28.2), P < 0.05.
      CONCLUSION: Ureteral stent retrieval using rigid ureteroscope under topical
      anesthesia is as safe and effective as flexible cystoscope but with a much lower
      cost to patients. TRIAL REGISTRATION: This study was registered with Chinese
      Clinical Trial Registry on March 27, 2017 (retrospective registration) with a
      trial registration number of ChiCTR-IOR-17010986 .

PMID- 28431539
TI  - Pain Intervention for people with Dementia in nursing homes (PID): study protocol
      for a quasi-experimental nurse intervention.
AB  - BACKGROUND: It is estimated that 19 to 83% of people with dementia suffer from
      pain that is inadequately treated in the last months of life. A large number of
      healthcare workers who care for these people in nursing homes lack appropriate
      expertise and may therefore not always recognise, assess and treat pain in those
      with dementia who have complex problems on time, properly and efficiently. The
      aim of this intervention trial is to identify care needs of people with dementia
      suffering from pain living in a nursing home. METHODS: A quasi-experimental nurse
      led intervention trial based on a convenience sample of four nursing homes in the
      Swiss Canton of Zurich examines the effects on dementia patients (n = 411), the
      healthcare institution and the qualification level of the healthcare workers
      compared to historical controls, using an event analysis and a multilevel
      analysis. Healthcare workers will be individually trained how to assess,
      intervene and evaluate acute and chronic pain. There are three data-monitoring
      cycles (T0, T1, T2) and two intervention cycles (I1, I2) with a total study
      duration of 425 days. There is also a process evaluation based on Dobbins
      analyses that analyse in particular the potentials for change in clinical
      practice of change agents. DISCUSSION: The aim of the intervention trial is to
      improve pain management strategies in older people with dementia in nursing
      homes. Clinically significant findings will be expected that will help reduce
      suffering in the sense of "total pain" for people with dementia. The joint intra-
      and interdisciplinary collaboration between practice and supply-oriented
      (nursing) research will have both a lasting effect on the efficiency measurement
      and provide scientifically sound results. Nursing homes can integrate the
      findings from the intervention trial into their internal quality control process.
      The potential for improvements can be directly influenced by the nursing home
      itself. TRIAL REGISTRATION: Registration trial number: DRKS00009726 on DRKS,
      registered 10 January 2017, retrorespectively registered. Clearance certificate
      is available of the ethics committees of the canton of Thurgau, Switzerland,
      number: TG K201-02, and Zurich, Switzerland, number: ZH 01-2016.

PMID- 28431540
TI  - Prevention of advanced glycation end-products formation in diabetic rats through
      beta-cell modulation by Aegle marmelos.
AB  - BACKGROUND: Although the anti-diabetic activity of Aegle marmelos (AM) is known,
      however, its anti-glycation activity is not reported yet. In this study, we have
      investigated its anti-glycation activity under in vitro and in vivo conditions
      and determined possible mechanism(s) in streptozotocin-induced diabetic rats.
      METHODS: Effective dose of AM (400 mg/kg) was administrated orally to diabetic
      rats for 42 days. Thereafter, blood glucose, serum insulin, HbA1c, antioxidant
      status, and advanced glycation end-products (AGEs) were measured. AGEs and its
      receptor (RAGE) in kidney were analyzed by immunohistochemistry and
      immunoblotting. Additionally, pancreatic sections were co-stained for insulin and
      glucagon and images were acquired using NIKON TE2000E fluorescence microscopy.
      RESULTS: Oral administration of AM extract resulted in a significant increase in
      serum insulin by better functioning of beta-cell and preserving pancreatic beta
      cell integrity in diabetic rats. Treatment of AM extract significantly (p =
      0.000) prevented the formation of HbA1c in the diabetic rats (8.20 +/- 0.18% vs.
      11.92 +/- 0.59%). The circulatory AGEs level found in diabetic rat was
      significantly (p = 0.002) attenuated by AM treatment (0.66 +/- 0.05 mg/ml vs.
      1.18 +/- 0.19 mg/ml). AM treatment also reduced AGEs accumulation around Bowman's
      capsule and in tubular basement membrane around arteries in diabetic rat kidney.
      The accumulation of RAGE was very similar to that of AGEs in diabetic rats and
      RAGE accumulation was also prevented by AM treatment. The extract showed potent
      antioxidant activity both under in vitro and in vivo systems. Eugenol, one of the
      active constituent of AM fruit extract, showed acute blood glucose-lowering
      activity in diabetic rats and enhanced glucose-stimulated insulin secretion from
      mice islets. CONCLUSION: AM extract prevents AGEs formation by modulating beta
      cell function, and eugenol may play important role in preventing complications of
      diabetes in this rat model.

PMID- 28431541
TI  - Strengthening the role of Community Health Representatives in the Navajo Nation.
AB  - BACKGROUND: Strengthening Community Health Worker systems has been recognized to
      improve access to chronicdisease prevention and management efforts in low
      resource communities. The Community Outreach and PatientEmpowerment (COPE)
      Program is a Native non-profit organization with formal partnerships with both
      the NavajoNation Community Health Representative (CHR) Program and the clinical
      facilities serving the Navajo Nation. COPEworks to better integrate CHRs into the
      local health care system through training, strengthening care coordination,and a
      standardized culturally appropriate suite of health promotion materials for CHRs
      to deliver to high-riskindividuals in their homes. METHODS: The objective of this
      mixed methods, cross sectional evaluation of a longitudinal cohort study was
      toexplore how the COPE Program has effected CHR teams over the past 6 years. COPE
      staff surveyed CHRs inconcurrent years (2014 and 2015) about their perceptions of
      and experience working with COPE, includingpotential effects COPE may have had on
      communication among patients, CHRs, and hospital-based providers. COPEstaff also
      conducted focus groups with all eight Navajo Nation CHR teams. RESULTS: CHRs and
      other stakeholders who viewed our results agree that COPE has improved clinic
      communitylinkages, primarily through strengthened collaborations between Public
      Health Nurses and CHRs, and access to theElectronic Health Records. CHRs
      perceived that COPE's programmatic support has strengthened their validity
      andreputation with providers and clients, and has enhanced their ability to
      positively effect health outcomes amongtheir clients. CHRs report an improved
      ability to deliver health coaching to their clients. Survey results show that
      80.2% of CHRs feel strongly positive that COPE trainings are useful, while 44.6%
      of CHRs felt that communication andteamwork had improved because of COPE.
      CONCLUSIONS: These findings suggest that CHRs have experienced positive benefits
      from COPE through training.COPE may provide a useful programmatic model on how
      best to support other Community Health Workersthrough strengthening clinic
      community linkages, standardizing competencies and training support, and
      structuringhome-based interventions for high-risk individuals.

PMID- 28431542
TI  - Effects of periodontal treatment on the medical status of patients with type 2
      diabetes mellitus: a pilot study.
AB  - BACKGROUND: Studies have demonstrated that periodontal disease is associated with
      the development of systemic complications in patients with type 2 diabetes
      mellitus (T2DM). The purpose of this pilot study was to investigate which markers
      among various systemic disease parameters are affected by periodontal treatment
      in patients with T2DM. METHODS: Twelve patients with T2DM were given oral hygiene
      instructions and subsequent subgingival scaling and root planing. The periodontal
      status was recorded, and blood and urine samples were taken to measure various
      parameters of glucose control and systemic status at baseline and 1 month
      following the periodontal treatment. Serum concentrations of tumor necrosis
      factor-alpha and high-sensitivity C-reactive protein were measured by enzyme
      linked immunosorbent assay. RESULTS: After the periodontal treatment, the
      glycated hemoglobin value was significantly improved. The levels of urinary N
      acetyl-beta-D-glucosaminidase and albumin, which are markers of renal
      dysfunction, also decreased significantly after treatment. Among the parameters
      measured in serum, the gamma-glutamyl transpeptidase level, which is usually
      interpreted as a marker of liver dysfunction, was significantly reduced. The
      serum concentrations of tumor necrosis factor-alpha and high-sensitivity C
      reactive protein were also significantly reduced by periodontal treatment.
      CONCLUSION: Within the limitations of this pilot study, periodontal treatment may
      be effective not only in improving metabolic control, but also in reducing the
      risk of diabetic kidney and liver disease in patients with T2DM.

PMID- 28431543
TI  - More complications in uncemented compared to cemented hemiarthroplasty for
      displaced femoral neck fractures: a randomized controlled trial of 201 patients,
      with one year follow-up.
AB  - BACKGROUND: It is unclear whether cemented or uncemented hemiarthroplasty is the
      best treatment option in elderly patients with displaced femoral neck fractures.
      Previous randomized trials comparing cemented and uncemented hemiarthroplasty
      have conflicting results. We conducted a randomized controlled trial to compare
      cemented and uncemented hemiarthroplasty. METHODS: This multicenter parallel
      randomized controlled trial included patients of 70 years and older with a
      displaced femoral neck fracture (Garden type III or IV). Inclusion was between
      August 2008 and June 2012. Patients were randomized between a cemented
      hemiarthroplasty, type Muller Straight Stem or an uncemented hemiarthroplasty,
      type DB-10. Primary outcomes were complications, operation time, functional
      outcome (measured by Timed-Up-and-Go (TUG) and Groningen Activity Restriction
      Scale (GARS)) and mid-thigh pain. Health Related Quality of Life (HRQoL,
      expressed with the SF-12) was measured as an secondary outcome. Follow up was 1
      year. RESULTS: In total 201 patients were included in the study (91 uncemented,
      110 cemented hemiarthroplasties) The uncemented group showed more major local
      complications (intra- and postoperative fractures and dislocations) odds ratio
      (95% confidence interval) 3.36 (1.40 to 8.11). There was no difference in mean
      operation time (57.3 vs 55.4 min). There were no differences in functional
      outcomes (TUG 12.8 (9.4) vs. 13.9 (9.0), GARS 43.2 (19.7) vs. 39.2 (16.5)) and
      mid-thigh pain (18.6 vs 21.6%). Physical component SF-12 HRQoLwas lower in the
      uncemented group (30.3 vs. 35.3 p < 0.05 after six weeks, 33.8 vs 38.5 p < 0.05
      after 12 weeks). CONCLUSION: A cemented hemiarthroplasty in elderly patients with
      a displaced femoral neck fracture results in less complications compared to an
      uncemented hemiarthroplasty. TRIAL REGISTRATION: Netherlands Trial Registry; NTR
      1508 , accepted date 27 okt 2008.

PMID- 28431545
TI  - Optimising spatial accessibility to inform rationalisation of specialist health
      services.
AB  - BACKGROUND: In an era of budget constraints for healthcare services, strategies
      for provision of services that improve quality whilst saving costs are highly
      valued. A proposed means to achieve this is consolidation of services into fewer
      specialist centres, but this may lead to reduced spatial accessibility. We
      describe a methodology which includes implementing a combinatorial optimisation
      algorithm to derive combinations of services which optimise spatial accessibility
      in the context of service rationalisation, and demonstrate its use through the
      exemplar of tuberculosis clinics in London. METHODS: Our methodology involves (1)
      identifying the spatial distribution of the patient population using the service;
      (2) calculating patient travel times to each service location, and (3) using a
      combinatorial optimisation algorithm to identify subsets of locations that
      minimise overall travel time. We estimated travel times for tuberculosis patients
      notified in London between 2010 and 2013 to each of 29 clinics in the city.
      Travel time estimates were derived from the Transport for London Journey Planner
      service. We identified the subset of clinics that would provide the shortest
      overall travel time for each possible number of clinic subsets (1-28). RESULTS:
      Based on the 29 existing clinic locations, mean estimated travel time to clinics
      used by 12,061 tuberculosis patients in London was 33 min; and mean time to their
      nearest clinics was 28 min. Using optimum combinations of clinic locations, and
      assuming that patients attended their nearest clinics, a mean travel time of less
      than 45 min could be achieved with three clinics; of 34 min with ten clinics, and
      of less than 30 min with 18 clinics. CONCLUSIONS: We have developed a
      methodological approach to optimise spatial accessibility which can be used to
      inform rationalisation of health services. In urban conurbations, this may enable
      service reorganisation which increases quality and efficiency without
      substantially affecting spatial accessibility. This approach could be used to
      inform planning of service reorganisations, but may not be generalisable to rural
      areas or smaller urban centres.

PMID- 28431544
TI  - Strategies for monitoring and combating resistance to combination kinase
      inhibitors for cancer therapy.
AB  - Targeted therapies such as kinase inhibitors and monoclonal antibodies have
      dramatically altered cancer care in recent decades. Although these targeted
      therapies have improved patient outcomes in several cancer types, resistance
      ultimately develops to these agents. One potential strategy proposed to overcome
      acquired resistance involves taking repeat tumor biopsies at the time of disease
      progression, to identify the specific molecular mechanism driving resistance in
      an individual patient and to select a new agent or combination of agents capable
      of surmounting that specific resistance mechanism. However, recent studies
      sampling multiple metastatic lesions upon acquired resistance, or employing
      "liquid biopsy" analyses of circulating tumor DNA, have revealed that multiple,
      heterogeneous resistance mechanisms can emerge in distinct tumor subclones in the
      same patient. This heterogeneity represents a major clinical challenge for
      devising therapeutic strategies to overcome resistance. In many cancers, multiple
      drug resistance mechanisms often converge to reactivate the original pathway
      targeted by the drug. This convergent evolution creates an opportunity to target
      a common signaling node to overcome resistance. Furthermore, integration of
      liquid biopsy approaches into clinical practice may allow real-time monitoring of
      emerging resistance alterations, allowing intervention prior to standard
      detection of radiographic progression. In this review, we discuss recent advances
      in understanding tumor heterogeneity and resistance to targeted therapies,
      focusing on combination kinase inhibitors, and we discuss approaches to address
      these issues in the clinic.

PMID- 28431546
TI  - Health care public reporting utilization - user clusters, web trails, and usage
      barriers on Germany's public reporting portal Weisse-Liste.de.
AB  - BACKGROUND: Quality of care public reporting provides structural, process and
      outcome information to facilitate hospital choice and strengthen quality
      competition. Yet, evidence indicates that patients rarely use this information in
      their decision-making, due to limited awareness of the data and complex and
      conflicting information. While there is enthusiasm among policy makers for public
      reporting, clinicians and researchers doubt its overall impact. Almost no study
      has analyzed how users behave on public reporting portals, which information they
      seek out and when they abort their search. METHODS: This study employs web-usage
      mining techniques on server log data of 17 million user actions from Germany's
      premier provider transparency portal Weisse-Liste.de (WL.de) between 2012 and
      2015. Postal code and ICD search requests facilitate identification of
      geographical and treatment area usage patterns. User clustering helps to identify
      user types based on parameters like session length, referrer and page topic
      visited. First-level markov chains illustrate common click paths and premature
      exits. RESULTS: In 2015, the WL.de Hospital Search portal had 2,750 daily users,
      with 25% mobile traffic, a bounce rate of 38% and 48% of users examining hospital
      quality information. From 2013 to 2015, user traffic grew at 38% annually. On
      average users spent 7 min on the portal, with 7.4 clicks and 54 s between clicks.
      Users request information for many oncologic and orthopedic conditions, for which
      no process or outcome quality indicators are available. Ten distinct user types,
      with particular usage patterns and interests, are identified. In particular, the
      different types of professional and non-professional users need to be addressed
      differently to avoid high premature exit rates at several key steps in the
      information search and view process. Of all users, 37% enter hospital information
      correctly upon entry, while 47% require support in their hospital search.
      CONCLUSIONS: Several onsite and offsite improvement options are identified.
      Public reporting needs to be directed at the interests of its users, with more
      outcome quality information for oncology and orthopedics. Customized reporting
      can cater to the different needs and skill levels of professional and non
      professional users. Search engine optimization and hospital quality advocacy can
      increase website traffic.

PMID- 28431547
TI  - The effectiveness of asking behaviors among 9-11 year-old children in increasing
      home availability and children's intake of fruit and vegetables: results from the
      Squire's Quest II self-regulation game intervention.
AB  - BACKGROUND: Home environment has an important influence on children's fruit and
      vegetable (FV) consumption, but children may in turn also impact their home FV
      environment, e.g. by asking for FV. The Squire's Quest II serious game
      intervention aimed to increase asking behaviors to improve home FV availability
      and children's FV intake. This study's aims were to assess: 1) did asking
      behaviors at baseline predict home FV availability at baseline (T0) (RQ1); 2)
      were asking behaviors and home FV availability influenced by the intervention
      (RQ2); 3) did increases in asking behaviors predict increased home FV
      availability (RQ3); and 4) did increases in asking behaviors and increases in
      home FV availability mediate increases in FV intake among children (RQ4)?
      METHODS: This is a secondary analysis of a study using a randomized controlled
      trial, with 4 groups (each n = 100 child-parent dyads). All groups were analyzed
      together for this paper since groups did not vary on components relevant to our
      analysis. All children and parents (n = 400 dyads) received a self-regulation
      serious game intervention and parent material. The intervention ran for three
      months. Measurements were taken at baseline, immediately after intervention and
      at 3-month follow-up. Asking behavior and home FV availability were measured
      using questionnaires; child FV intake was measured using 24-h dietary recalls.
      ANCOVA methods (research question 1), linear mixed-effect models (research
      question 2), and Structural Equation Modeling (research questions 3 and 4) were
      used. RESULTS: Baseline child asking behaviors predicted baseline home FV
      availability. The intervention increased child asking behaviors and home FV
      availability. Increases in child asking behaviors, however, did not predict
      increased home FV availability. Increased child asking behaviors and home FV
      availability also did not mediate the increases in child FV intake. CONCLUSIONS:
      Children influence their home FV environment through their asking behaviors,
      which can be enhanced via a serious game intervention. The obtained increases in
      asking behavior were, however, insufficient to affect home FV availability or
      intake. Other factors, such as child preferences, sample characteristics,
      intervention duration and parental direct involvement may play a role and warrant
      examination in future research. TRIALS REGISTRATION: ClinicalTrials.gov
      NCT01004094 . Date registered 10/28/2009.

PMID- 28431548
TI  - Water-pipe smoke condensate increases the internalization of Mycobacterium Bovis
      of type II alveolar epithelial cells (A549).
AB  - BACKGROUND: Tuberculosis (TB) is a major global health problem, and there is an
      association between tobacco smoke and TB. Water pipe smoking has become an
      increasing problem not only in Middle Eastern countries but also globally because
      users consider it as safer than cigarettes. The presence of high levels of toxic
      substances in water-pipe smoke may be a predisposing factor that enhances the
      incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in
      alveolar epithelial cells following exposure to water-pipe smoke may predispose
      subjects to pulmonary infection. Here, we studied the effects of water-pipe
      condense (WPC) on the internalization of Mycobacterium Bovis BCG by
      macropinocytosis in the alveolar epithelial cell line A549. METHODS: A549 cells
      were exposed to WPC (4 mg/ml) for 24, 48, 72 and 96 h. Cell viability was studied
      using the methyl thiazolyldipenyl-tetrazolium bromide (MTT) reduction assay and
      proliferation by bromodeoxyUridine (BrdU) incorporation. Cells were exposed to
      FITC-Dextran (1 mg/ml) (as a control) and FITC-BCG (MOI = 10) for 20 min at 37 
      degrees C before cells were collected and the uptake of BCG-FITC determined by
      flow cytometry. Similar experiments were performed at 4  degrees C as a control.
      The Rho-associated protein kinase (ROCK) inhibitor Y-27632 (1 MUM) was used to
      assess the mechanism by which WPC enhanced BCG uptake. RESULTS: WPC (4 mg/ml)
      increased the uptake of BCG-FITC after 72 (1.3 +/- 0.1 fold, p < 0.05) and 96
      (1.4 +/- 0.05 fold, p < 0.05) hours. No effect on BCG-FITC uptake was observed at
      24 or 48 h. WPC also significantly increased the uptake of FITC-Dextran (2.9 +/-
      0.3 fold, p < 0.05) after 24 h. WPC significantly decreased cell viability after
      24 (84 +/- 2%, p < 0.05), 48 (78+/-, 3%, p < 0.05), 72 (64 +/- 2%, p < 0.05) and
      96 h (45 +/- 2%, p < 0.05). Y-27632 completely attenuated the increased uptake of
      BCG by WPC. Cell proliferation showed a decreasing trend in a time-dependent
      manner with WPC exposure. CONCLUSION: WPC exposure increased epithelial cell
      endocytosis activity and death as well as enhancing their capacity for
      macropinocytosis. Our in vitro data indicates possible harmful effects of WPC on
      the ability of lung epithelial cells to phagocytose mycobacterium.

PMID- 28431549
TI  - Household food insecurity is associated with abdominal but not general obesity
      among Iranian children.
AB  - BACKGROUND: Childhood obesity is increasing all over the world. Food insecurity
      is mentioned as a possible risk factor; however, previous studies have led to
      inconsistent results in different societies while data are lacking for the Middle
      East. We aimed to investigate the relationship between food insecurity and
      general or abdominal obesity in Iranian children in a cross-sectional study.
      METHODS: Anthropometric data including height, weight, and waist circumference
      were measured by trained nutritionists. General and abdominal obesity were
      defined based on world health organization (WHO) and Iranian reference curves for
      age and gender, respectively. Radimer/Cornell food security questionnaire was
      filled by parents. Data about the physical activity of participants, family socio
      economic status, parental obesity and data about perinatal period were also
      gathered using self-administered questionnaires. Logistic regression was
      incorporated to investigate the association between food insecurity and obesity
      in crude and multi-variable adjusted models. RESULTS: A total of 587 children
      aged 9.30 +/- 1.49 years had complete data for analysis. Food insecurity at
      household level was significantly associated with abdominal obesity (odds ratio
      (OR) = 1.54; confidence interval (CI):1.01-2.34, p <0.05) and the relationship
      remained significant after adjusting for all potential confounding variables (OR
      = 2.02; CI:1.01-4.03, p <0.05). Food insecurity was associated with general
      obesity neither in crude analysis and multi-variable adjusted models.
      CONCLUSIONS: The slight levels of food insecurity might increase the likelihood
      of abdominal obesity in Iranian children and macroeconomic policies to improve
      the food security are necessary. Large-scale prospective studies, particularly in
      the Middle East, are highly recommended to confirm our results.

PMID- 28431550
TI  - The physiological cost of male-biased parasitism in a nearly monomorphic mammal.
AB  - BACKGROUND: Even though male-biased parasitism is common in mammals, little
      effort has been made to evaluate whether higher parasitic burden in males results
      in an extra biological cost, and thus a decrease in fitness. Body condition
      impairment and the augmentation of oxidative stress can be used as indicators of
      the cost of parasite infections. Here, we examined relationships between
      gastrointestinal and respiratory helminths, body condition and oxidative stress
      markers (glutathione peroxidase, paraoxonase-1) in 28 Pyrenean chamois (Rupicapra
      p. pyrenaica) sampled in autumn. RESULTS: Only male chamois showed a reduction in
      body condition and higher oxidative stress due to parasite infection, likely
      because of the extremely high parasite burdens observed in males. CONCLUSIONS:
      This study made evident a disparity in the physiological cost of multiple
      parasitism between sexes in a wild mammal, mainly due to parasitic richness.
      Because of the similar life expectancy in male and female chamois, we suggest
      that males may have developed natural mechanisms to compensate for higher
      parasite loads during the rut.

PMID- 28431552
TI  - Strategies to improve engagement of 'hard to reach' older people in research on
      health promotion: a systematic review.
AB  - BACKGROUND: This systematic review aimed to identify facilitators, barriers and
      strategies for engaging 'hard to reach' older people in research on health
      promotion; the oldest old (>=80 years), older people from black and minority
      ethnic groups (BME) and older people living in deprived areas. METHODS: Eight
      databases were searched to identify eligible studies using quantitative,
      qualitative, and mixed research methods. Using elements of narrative synthesis,
      engagement strategies, and reported facilitators and barriers were identified,
      tabulated and analysed thematically for each of the three groups of older people.
      RESULTS: Twenty-three studies (3 with oldest-old, 16 with BME older people, 2
      within deprived areas, 1 with both oldest-old and BME, 1 with both BME and
      deprived areas) were included. Methods included 10 quantitative studies (of which
      1 was an RCT), 12 qualitative studies and one mixed-methods study. Facilitators
      for engaging the oldest old included gaining family support and having flexible
      sessions. Facilitators for BME groups included building trust through known
      professionals/community leaders, targeting personal interests, and addressing
      ethnic and cultural characteristics. Among older people in deprived areas,
      facilitators for engagement included encouragement by peers and providing
      refreshments. Across all groups, barriers for engagement were deteriorating
      health, having other priorities and lack of transport/inaccessibility. Feeling
      too tired and lacking support from family members were additional barriers for
      the oldest old. Similarly, feeling too tired and too old to participate in
      research on health promotion were reported by BME groups. Barriers for BME groups
      included lack of motivation and self-confidence, and cultural and language
      differences. Barriers identified in deprived areas included use of written
      recruitment materials. Strategies to successfully engage with the oldest old
      included home visits and professionals securing consent if needed. Strategies to
      engage older people from BME groups included developing community connections and
      organising social group sessions. Strategies to engage with older people in
      deprived areas included flexibility in timing and location of interventions.
      CONCLUSIONS: This review identified facilitators, barriers and strategies for
      engaging 'hard to reach' older people in health promotion but research has been
      mainly descriptive and there was no high quality evidence on the effectiveness of
      different approaches.

PMID- 28431551
TI  - Guided Internet-based versus face-to-face clinical care in the management of
      tinnitus: study protocol for a multi-centre randomised controlled trial.
AB  - BACKGROUND: Innovative strategies are required to improve access to evidence
      based tinnitus interventions. A guided Internet-based cognitive behavioural
      therapy (iCBT) intervention for tinnitus was therefore developed for a U.K.
      POPULATION: Initial clinical trials indicated efficacy of iCBT at reducing
      tinnitus severity and associated comorbidities such as insomnia and depression.
      The aim of this phase III randomised controlled trial is to compare this new iCBT
      intervention with an established intervention, namely face-to-face clinical care
      for tinnitus. METHODS/DESIGN: This will be a multi-centre study undertaken across
      three hospitals in the East of England. The design is a randomised, two-arm,
      parallel-group, non-inferiority trial with a 2-month follow-up. The experimental
      group will receive the guided iCBT intervention, whereas the active control group
      will receive the usual face-to-face clinical care. An independent researcher will
      randomly assign participants, using a computer-generated randomisation schedule,
      after stratification for tinnitus severity. There will be 46 participants in each
      group. The primary assessment measure will be the Tinnitus Functional Index. Data
      analysis will establish whether non-inferiority is achieved using a pre-defined
      non-inferiority margin. DISCUSSION: This protocol outlines phase III of a
      clinical trial comparing a new iCBT with established face-to-face care for
      tinnitus. If guided iCBT for tinnitus proves to be as effective as the usual
      tinnitus care, it may be a viable additional management route for individuals
      with tinnitus. This could increase access to evidence-based effective tinnitus
      care and reduce the pressures on existing health care systems. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT02665975 . Registered on 22
      January 2016.

PMID- 28431553
TI  - Long working hours in the healthcare system of the Belo Horizonte municipality,
      Brazil: a population-based cross-sectional survey.
AB  - BACKGROUND: Health personnel are key players in developing and improving
      healthcare systems, caring for individuals and their communities, and helping
      improve quality of life. However, these professionals are often exposed to long
      working hours because of the pressing need for their services at potentially any
      time of day. The long working hours they endure are a major risk factor for both
      acute and chronic health problems. The present study aimed to analyze occurrences
      of long working hours and their association with individual characteristics and
      employment factors among workers in the municipal healthcare system in Belo
      Horizonte, Brazil. METHODS: In this cross-sectional study, a ramdomly selected
      proportional sample of 1549 participants was analyzed from among the total of 13
      602 workers in the Belo Horizonte municipal healthcare system in 2009. "Long"
      working hours were defined as >44 h/week. A self-administered questionnaire was
      used for accumulating data. Associations with outcomes were estimated using
      logistic regression, in univariate and multivariate models. RESULTS: The rate of
      occurrence of long working hours was 31.4% (95% CI 29.1-33.7). Lower educational
      level (high school, technical, or uncompleted undergraduate [OR 0.60, 95% CI 0.47
      0.78 p < 0.001], or elementary [OR 0.33, 95% CI 0.19-0.55 p < 0.001]) was
      associated with a lower likelihood of self-reporting long working hours in
      relation to the group with the highest educational level (completed undergraduate
      or postgraduate). Male sex (OR 1.62, 95% CI 1.26-2.09 p < 0.001), having children
      (PR 1.54, 95% CI 1.20-1.97 p = 0.001), and being in the healthcare provider group
      (OR 1.82, 95% CI 1.40-2.35 p < 0.001) were factors associated with greater
      likelihood of long working hours. CONCLUSIONS: It was observed that number of
      long weekly working hours was related to individual characteristics and
      employment factors.

PMID- 28431554
TI  - A need to accelerate health research productivity in an African University: the
      case of Makerere University College of Health Sciences.
AB  - BACKGROUND: In the last decade, Makerere University College of Health Sciences
      (MakCHS) has taken strides in research and training to improve healthcare through
      collaborative training and research programs. However, there is limited data on
      the trends of MakCHS faculty contributions to research and on faculty growth to
      take leading roles in health research. This paper reviews MakCHS faculty research
      publications over 15.5 years and outlines possible strategies to enhance faculty
      research outputs. METHODS: We used a mixed methods approach. A systematic review
      of research publications by faculty at MakCHS (PubMed and Google Scholar from
      January 1, 2000, to June 30, 2015) to quantify the number of research articles,
      areas researched, authorship contribution by MakCHS faculty, source of funding,
      as well as affiliated local and international collaborations. Graphs were used to
      shown trends in publications and leadership of authorship by faculty. Annual
      individual faculty research productivity was presented as publication per capita.
      Qualitative data on high priority needs to improve research outputs was collected
      through focus group discussions (FGDs) with faculty members, and analysed
      manually into emerging themes. RESULTS: Of 298 faculty at MakCHS at 2015, 89
      (30%) were female and 229 (77%) were junior and mid-level faculty (senior
      lecturer and below). The PubMed and Google Scholar searches yielded 6927
      published articles, of which 3399 (49%) full-text articles were downloaded for
      analysis, 426/3825 (11%) available as titles/abstracts only, and 598/4423 (14%)
      were excluded. Only 614 articles were published in 2014, giving a publication per
      capita of 2.1 for any authorship, and 0.3 for first and last authorship
      positions. MakCHS faculty increasingly contributed as first, second, third, and
      last authors. Up to 57% of research was in infectious diseases, followed by non
      communicable diseases (20%) and non-communicable maternal child health (11%).
      Priority needs to improve research outputs, as expressed by faculty, were (1) an
      institutionally led faculty career development program, (2) skills building in
      research methods and scientific writing, (3) protected time for research related
      activities, (4) opportunities for collaborative research, and (5) use of
      individual development plans. CONCLUSION: Faculty research productivity was low
      and dominated by infectious diseases and non-communicable disease research. There
      is a need for structured institutional support to optimise faculty research
      outputs. Only with increased research productivity will MakCHS and other academic
      institutions be able to make a significant contribution in addressing national
      health challenges.

PMID- 28431555
TI  - Reduction of pulmonary toxicity of metal oxide nanoparticles by phosphonate-based
      surface passivation.
AB  - BACKGROUND: The wide application of engineered nanoparticles has induced
      increasing exposure to humans and environment, which led to substantial concerns
      on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells
      and animals, thus safe designs of MOx with reduced hazard potential are desired.
      Currently, there is a lack of a simple yet effective safe design approach for the
      toxic MOx. In this study, we determined the key physicochemical properties of MOx
      that lead to cytotoxicity and explored a safe design approach for toxic MOx by
      modifying their hazard properties. RESULTS: THP-1 and BEAS-2B cells were exposed
      to 0-200 MUg/mL MOx for 24 h, we found some toxic MOx including CoO, CuO, Ni2O3
      and Co3O4, could induce reactive oxygen species (ROS) generation and cell death
      due to the toxic ion shedding and/or oxidative stress generation from the active
      surface of MOx internalized into lysosomes. We thus hypothesized that surface
      passivation could reduce or eliminate the toxicity of MOx. We experimented with a
      series of surface coating molecules and discovered that ethylenediamine tetra
      (methylene phosphonic acid) (EDTMP) could form stable hexadentate coordination
      with MOx. The coating layer can effectively reduce the surface activity of MOx
      with 85-99% decrease of oxidative potential, and 65-98% decrease of ion shedding.
      The EDTMP coated MOx show negligible ROS generation and cell death in THP-1 and
      BEAS-2B cells. The protective effect of EDTMP coating was further validated in
      mouse lungs exposed to 2 mg/kg MOx by oropharyngeal aspiration. After 40 h
      exposure, EDTMP coated MOx show significant decreases of neutrophil counts,
      lactate dehydrogenase (LDH) release, MCP-1, LIX and IL-6 in bronchoalveolar
      lavage fluid (BALF), compared to uncoated particles. The haematoxylin and eosin
      (H&E) staining results of lung tissue also show EDTMP coating could significantly
      reduce the pulmonary inflammation of MOx. CONCLUSIONS: The surface reactivity of
      MOx including ion shedding and oxidative potential is the dominated
      physicochemical property that is responsible for the cytotoxicity induced by MOx.
      EDTMP coating could passivate the surface of MOx, reduce their cytotoxicity and
      pulmonary hazard effects. This coating would be an effective safe design approach
      for a broad spectrum of toxic MOx, which will facilitate the safe use of MOx in
      commercial nanoproducts.

PMID- 28431556
TI  - Factors associated with loss to follow-up after occupational HIV exposure in Cape
      Town, South Africa: a retrospective cohort study.
AB  - BACKGROUND: There is limited data on factors associated with loss to follow-up
      (LTFU) of health care workers (HCWs) following occupational exposure to HIV, and
      most studies were conducted in an era when poorly tolerated antiretrovirals like
      zidovudine were used. METHODS: A retrospective cohort study was conducted of HCWs
      attending a referral hospital's Occupational Health Clinic in Cape Town, South
      Africa for post-exposure prophylaxis (PEP) during a period when tenofovir was
      available. Our primary outcome was LTFU at the 3-month visit. We selected seven
      variables a priori for our logistic regression model and ensured there were at
      least 10 outcome events per variable to minimize bias. RESULTS: Two hundred and
      ninety-three folders were evaluated for descriptive analysis. LTFU worsened with
      successive visits: 36% at 6 weeks, 60% at 3 months, and 72% at 6 months. In
      multivariate analysis at the 3-month visit LTFU was associated with age (adjusted
      odds ratio (aOR), 0.6 per 10-year increase [95% CI, 0.5-0.9]), HCW category of
      doctor (aOR 2.7 [95% CI, 1.3-5.5]), and time from exposure to receiving PEP of
      more than 24 h (aOR 5.9 [95% CI, 1.3-26.9]). CONCLUSION: We identified factors
      associated with LTFU of HCWs after occupational HIV exposure, which could be used
      to target interventions to improve follow-up.

PMID- 28431557
TI  - The effect of vitamin B12 supplementation in Nepalese infants on growth and
      development: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Vitamin B12 deficiency is one of the most common micronutrient
      deficiencies and is associated with poor cognitive development and growth.
      Vitamin B12 is crucial for normal cell division and differentiation, and it is
      necessary for the development and myelination of the central nervous system. The
      aim of the present study is to measure the effect of daily supplementation of
      vitamin B12 on the neurodevelopment and growth of young children in Nepal.
      METHODS/DESIGN: We are conducting an individually randomized, double-blind,
      placebo-controlled trial with 600 marginally stunted children 6-11 months old
      (length for age less than -1 z-score). Children are randomized to receive a lipid
      based paste containing vitamin B12 or placebo daily for 12 months. The main
      outcomes are changes in growth (z-scores) and in neurodevelopment measured by the
      Bayley Scales of Infant and Toddler Development, Third Edition, from baseline
      until the end of the study. DISCUSSION: If vitamin B12 supplementation benefits
      early child development and growth, this will have consequences for dietary
      recommendations for malnourished children worldwide. TRIAL REGISTRATIONS:
      ClinicalTrials.gov Identifier: NCT02272842 . Registered on 21 October 2014.
      Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014.

PMID- 28431558
TI  - Epidemiology and genotype distribution of human papillomavirus (HPV) in Southwest
      China: a cross-sectional five years study in non-vaccinated women.
AB  - BACKGROUND: Large-size data on type-specific HPV prevalence in Southwest China
      are required to estimate the cervical cancer burden in the country and to prepare
      for HPV-based cervical screening program and further HPV vaccination of China.
      This HPV study is a pooled analysis of data from five years in Chongqing of
      China, which is cross-sectional in design using data collecting. RESULTS: The
      positivity of HPV was 26.2% (10542/40311), single type was 25.7% (10360/40311),
      multiple type was 8.2% (3306/40311), high-risk HPV was 30.9% (12490/40311), and
      low-risk HPV was 2.9%(1169/40311). The most common genotypes were HPV16,52,58 and
      18. HPV-positive women (n = 10542) were triaged by cytology, colposcopy or
      histological diagnosis. Among HPV-positive women, 43.8% had normal, 22.5% had
      ASCUS, 0.2% had LSIL, 12.6% had HSIL and 6.0% had ICC. The most common HPV
      genotypes were HPV16, 58 and 18 in ASCUS, HPV16, 18 and 58 in LSIL, HPV16, 58 and
      33 in HSIL, and HPV16, 58 and 18 in ICC. The prevalence of Group 1/2A HPV types
      increased with increasing CIN grade and accounted for 96.05% of the CIN 3+
      lesions, while HPV16 accounted for 71.1%. HPV-positive women steadily increased
      with age, peaking at 31-40 years. CONCLUSION: The type-specific prevalence rate
      of HPV 16 and HPV 18 were a little lower than the mean of international meta
      analyses. Single HPV genotype infection was predominantly detected in different
      groups of cervical lesions in Chongqing, and HPV16, 52, 58 were the priority HPV
      types. The HPV genotyping study was found to be valuable for planning further
      preventive program for cervical cancer.

PMID- 28431559
TI  - Effects of whole grain rye, with and without resistant starch type 2
      supplementation, on glucose tolerance, gut hormones, inflammation and appetite
      regulation in an 11-14.5 hour perspective; a randomized controlled study in
      healthy subjects.
AB  - BACKGROUND: The prevalence of obesity is increasing worldwide and prevention is
      needed. Whole grain has shown potential to lower the risk of obesity,
      cardiovascular disease and type 2 diabetes. One possible mechanism behind the
      benefits of whole grain is the gut fermentation of dietary fiber (DF), e.g. non
      starch polysaccharides and resistant starch (RS), in whole grain. The purpose of
      the study is to investigate the effect of whole grain rye-based products on
      glucose- and appetite regulation. METHOD: Twenty-one healthy subjects were
      provided four rye-based evening test meals in a crossover overnight study design.
      The test evening meals consisted of either whole grain rye flour bread (RFB) or a
      1:1 ratio of whole grain rye flour and rye kernels bread (RFB/RKB), with or
      without added resistant starch (+RS). White wheat flour bread (WWB) was used as
      reference evening meal. Blood glucose, insulin, PYY, FFA, IL-6 as well as breath
      H2 and subjective rating of appetite were measured the following morning at
      fasting and repeatedly up to 3.5 h after a standardized breakfast consisting of
      WWB. Ad libitum energy intake was determined at lunch, 14.5 h after evening test
      and reference meals, respectively. RESULTS: The evening meal with RFB/RKB + RS
      decreased postprandial glucose- and insulin responses (iAUC) (P < 0.05) and
      increased the gut hormone PYY in plasma the following morning 0-120 min after the
      standardized breakfast, compared to WWB (P = 0.01). Moreover, RFB increased
      subjective satiety and decreased desire to eat, and both RFB and RFB/RKB
      decreased feeling of hunger (AUC 0-210 min). All rye-based evening meals
      decreased or tended to decrease fasting FFA (P < 0.05, RFB/RKB: P = 0.057) and
      increased breath hydrogen concentration (0-120 min, P < 0.001). No effects were
      noted on energy intake at lunch or inflammatory marker IL-6 (0 + 180 min) after
      the rye-based evening meals, compared to WWB. CONCLUSION: Whole grain rye bread
      has the potential to improve cardiometabolic variables in an 11-14.5 h
      perspective in healthy humans. The combination RFB/RKB + RS positively affected
      biomarkers of glucose- and appetite regulation in a semi-acute perspective.
      Meanwhile, RFB and RFB/RKB improved subjective appetite ratings. The effects
      probably emanate from gut fermentation events. TRIAL REGISTRATION: The study was
      registered at: ClinicalTrials.gov, register number NCT02347293 (
      www.clinicaltrials.gov/ct2/show/NCT02347293 ). Registered 15 January 2015.

PMID- 28431560
TI  - A new-generation of Bacillus subtilis cell factory for further elevated scyllo
      inositol production.
AB  - BACKGROUND: A stereoisomer of inositol, scyllo-inositol (SI), has been regarded
      as a promising therapeutic agent for Alzheimer's disease. However, this compound
      is relatively rare, whereas another stereoisomer of inositol, myo-inositol (MI)
      is abundant in nature. Bacillus subtilis 168 has the ability to metabolize
      inositol stereoisomers, including MI and SI. Previously, we reported a B.
      subtilis cell factory with modified inositol metabolism that converts MI into SI
      in the culture medium. The strain was constructed by deleting all genes related
      to inositol metabolism and overexpressing key enzymes, IolG and IolW. By using
      this strain, 10 g/l of MI initially included in the medium was completely
      converted into SI within 48 h of cultivation in a rich medium containing 2% (w/v)
      Bacto soytone. RESULTS: When the initial concentration of MI was increased to 50
      g/l, conversion was limited to 15.1 g/l of SI. Therefore, overexpression systems
      of IolT and PntAB, the main transporter of MI in B. subtilis and the membrane
      integral nicotinamide nucleotide transhydrogenase in Escherichia coli
      respectively, were additionally introduced into the B. subtilis cell factory, but
      the conversion efficiency hardly improved. We systematically determined the
      amount of Bacto soytone necessary for ultimate conversion, which was 4% (w/v). As
      a result, the conversion of SI reached to 27.6 g/l within 48 h of cultivation.
      CONCLUSIONS: The B. subtilis cell factory was improved to yield a SI production
      rate of 27.6 g/l/48 h by simultaneous overexpression of IolT and PntAB, and by
      addition of 4% (w/v) Bacto soytone in the conversion medium. The concentration of
      SI was increased even in the stationary phase perhaps due to nutrients in the
      Bacto soytone that contribute to the conversion process. Thus, MI conversion to
      SI may be further optimized via identification and control of these unknown
      nutrients.

PMID- 28431561
TI  - The evaluation of the role of medial collateral ligament maintaining knee
      stability by a finite element analysis.
AB  - BACKGROUND: A three-dimensional finite element model (FEM) of the knee joint was
      established to analyze the biomechanical functions of the superficial and deep
      medial collateral ligaments (MCLs) of knee joints and to investigate the
      treatment of the knee medial collateral ligament injury. METHODS: The right knee
      joint of a healthy male volunteer was subjected to CT and MRI scans in the
      extended position. The scanned data were imported into MIMICS, Geomagic, and
      ANSYS software to establish a three-dimensional FEM of the human knee joint. The
      anterior-posterior translation, valgus-varus rotation, and internal-external
      rotation of knee joints were simulated to observe tibial displacement or valgus
      angle. In addition, the magnitude and distribution of valgus stress in the
      superficial and deep layers of the intact MCL as well as the superficial, deep,
      and overall deficiencies of the MCL were investigated. RESULTS: In the extended
      position, the superficial medial collateral ligament (SMCL) would withstand
      maximum stresses of 48.63, 16.08, 17.23, and 16.08 MPa in resisting the valgus of
      knee joints, tibial forward displacement, internal rotation, and external
      rotation, respectively. Meanwhile, the maximum stress tolerated by the SMCL in
      various ranges of motion mainly focused on the femoral end point, which was
      located at the anterior and posterior parts of the femur in resisting valgus
      motion and external rotation, respectively. However, the deep medial collateral
      ligament could tolerate only minimum stress, which was mainly focused at the
      femoral start and end points. CONCLUSIONS: This model can effectively analyze the
      biomechanical functions of the superficial and deep layers of the MCLs of knee
      joints. The results show that the knee MCL II degrees  injury is the indication
      of surgical repair.

PMID- 28431562
TI  - Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2)
      gene on the lung.
AB  - BACKGROUND: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification
      of aldehydes. High expression of ALDHs is a marker for stem cells of many organs
      including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in
      inactivation of the enzyme and is associated with alcohol flushing syndrome and
      increased risk for cardiovascular and Alzheimer's diseases and some cancers. The
      effect of this ALDH2 polymorphism on the lung and its stem cells has not been
      thoroughly examined. METHODS: We examined the association between the ALDH2*2
      allele and lung function parameters in a population of healthy individuals. We
      also examined its association with the incidence of asthma and COPD in patient
      cohorts. We used the in vitro colony forming assay to detect the effect of the
      polymorphism on lung epithelial stem cells from both primary human surgical
      samples and Aldh2*2 transgenic (Tg) and Aldh2 -/- mice. Response to acute and
      chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 
      /- mice. RESULTS: In humans, the ALDH2*2 allele was associated with lower
      FEV1/FVC in the general population, but not with the development of asthma or
      COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a
      tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In
      mice, the tracheal epithelial thickness, nuclear density, and number of basal
      stem cells were significantly lower in Aldh2 -/- and Aldh2*2 Tg adult mice than
      in WT. Electron microscopy showed significantly increased number of
      morphologically abnormal mitochondria in the trachea of Aldh2 -/- mice. Aldh2 -/-
      tracheal and lung cells showed higher ROS levels and fewer functional
      mitochondria than those from WT mice. No significant differences were detected
      when tracheal and lung epithelial stem cells were examined for their in vitro
      CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to
      emphysema development, whereas influenza infection caused more epithelial damage
      in Aldh2 -/- mice than in WT mice. CONCLUSIONS: ALDH2 polymorphism has several
      subtle effects on the lungs, some of which are similar to changes observed during
      normal aging, suggesting a "premature lung aging" effect.

PMID- 28431563
TI  - Inheritance of brewing-relevant phenotypes in constructed Saccharomyces
      cerevisiae * Saccharomyces eubayanus hybrids.
AB  - BACKGROUND: Interspecific hybridization has proven to be a potentially valuable
      technique for generating de novo lager yeast strains that possess diverse and
      improved traits compared to their parent strains. To further enhance the value of
      hybridization for strain development, it would be desirable to combine phenotypic
      traits from more than two parent strains, as well as remove unwanted traits from
      hybrids. One such trait, that has limited the industrial use of de novo lager
      yeast hybrids, is their inherent tendency to produce phenolic off-flavours; an
      undesirable trait inherited from the Saccharomyces eubayanus parent. Trait
      removal and the addition of traits from a third strain could be achieved through
      sporulation and meiotic recombination or further mating. However, interspecies
      hybrids tend to be sterile, which impedes this opportunity. RESULTS: Here we
      generated a set of five hybrids from three different parent strains, two of which
      contained DNA from all three parent strains. These hybrids were constructed with
      fertile allotetraploid intermediates, which were capable of efficient
      sporulation. We used these eight brewing strains to examine two brewing-relevant
      phenotypes: stress tolerance and phenolic off-flavour formation. Lipidomics and
      multivariate analysis revealed links between several lipid species and the
      ability to ferment in low temperatures and high ethanol concentrations.
      Unsaturated fatty acids, such as oleic acid, and ergosterol were shown to
      positively influence growth at high ethanol concentrations. The ability to
      produce phenolic off-flavours was also successfully removed from one of the
      hybrids, Hybrid T2, through meiotic segregation. The potential application of
      these strains in industrial fermentations was demonstrated in wort fermentations,
      which revealed that the meiotic segregant Hybrid T2 not only didn't produce any
      phenolic off-flavours, but also reached the highest ethanol concentration and
      consumed the most maltotriose. CONCLUSIONS: Our study demonstrates the
      possibility of constructing complex yeast hybrids that possess traits that are
      relevant to industrial lager beer fermentation and that are derived from several
      parent strains. Yeast lipid composition was also shown to have a central role in
      determining ethanol and cold tolerance in brewing strains.

PMID- 28431564
TI  - Effectiveness of the capsaicin 8% patch in the management of peripheral
      neuropathic pain in European clinical practice: the ASCEND study.
AB  - BACKGROUND: In randomised studies, the capsaicin 8% patch has demonstrated
      effective pain relief in patients with peripheral neuropathic pain (PNP) arising
      from different aetiologies. METHODS: ASCEND was an open-label, non-interventional
      study of patients with non-diabetes-related PNP who received capsaicin 8% patch
      treatment, according to usual clinical practice, and were followed for <=52
      weeks. Co-primary endpoints were percentage change in the mean numeric pain
      rating scale (NPRS) 'average daily pain' score from baseline to the average of
      Weeks 2 and 8 following first treatment; and median time from first to second
      treatment. The primary analysis was intended to assess analgesic equivalence
      between post-herpetic neuralgia (PHN) and other PNP aetiologies. Health-related
      quality of life (HRQoL, using EQ-5D), Patient Global Impression of Change (PGIC)
      and tolerability were also assessed. RESULTS: Following first application,
      patients experienced a 26.6% (95% CI: 23.6, 29.62; n = 412) reduction in mean
      NPRS score from baseline to Weeks 2 and 8. Equivalence was demonstrated between
      PHN and the neuropathic back pain, post-operative and post-traumatic neuropathic
      pain and 'other' PNP aetiology subgroups. The median time from first to second
      treatment was 191 days (95% CI: 147, 235; n = 181). Forty-four percent of all
      patients were responders (>=30% reduction in NPRS score from baseline to Weeks 2
      and 8) following first treatment, and 86.9% (n = 159/183) remained so at Week 12.
      A sustained pain response was observed until Week 52, with a 37.0% (95% CI: 31.3,
      42.7; n = 176) reduction in mean NPRS score from baseline. Patients with the
      shortest duration of pain (0-0.72 years) experienced the highest pain response
      from baseline to Weeks 2 and 8. Mean EQ-5D index score improved by 0.199 utils
      (responders: 0.292 utils) from baseline to Week 2 and was maintained until Week
      52. Most patients reported improvements in PGIC at Week 2 and at all follow-up
      assessments regardless of number of treatments received. Adverse events were
      primarily mild or moderate reversible application site reactions. CONCLUSION: In
      European clinical practice, the capsaicin 8% patch provided effective and
      sustained pain relief, substantially improved HRQoL, improved overall health
      status and was generally well tolerated in a heterogeneous PNP population. TRIAL
      REGISTRATION: NCT01737294 Date of registration - October 22, 2012.

PMID- 28431565
TI  - Traditional Birth Attendant reorientation and Motherpacks incentive's effect on
      health facility delivery uptake in Narok County, Kenya: An impact analysis.
AB  - BACKGROUND: A community health programme in Narok County in Kenya aimed to
      improve skilled birth assistance during childbirth through two demand side
      interventions. First, traditional birth attendants (TBAs) were co-opted into
      using their influence to promote use of skilled birth attendants (SBAs) at health
      facilities during delivery, and to accompany pregnant women to health facilities
      in return for a Ksh500 (Approximately USD5 as of August 2016) cash incentive for
      each pregnant mother they accompanied. Secondly, a free Motherpack consisting of
      a range of baby care items was given to each mother after delivering at a health
      facility. This paper estimates the impact of these two interventions on trends of
      facility deliveries over a 36-month period here. METHODS: Dependency or inferred
      causality was estimated between reorientation of TBAs and provision of
      Motherpacks with changes in facility delivery numbers. The outcome variable
      consists of monthly facility delivery data from 28 health facilities starting
      from January 2013 to December 2015 obtained from the District Health Information
      Systems 2 (DHIS2). Data were collected on the 13th, 14th or 15th of each month,
      resulting in a total of 35 collections, over 35 months. The intervention data
      consisted of the starting month for each of the two interventions at each of the
      28 facilities. A negative binomial generalized linear model framework is applied
      to model the relationship as all variables were measured as count data and were
      overdispersed. All analyses were conducted using R software. FINDINGS: During the
      35 months considered, a total of 9095 health facility deliveries took place, a
      total of 408 TBAs were reached, and 2181 Motherpacks were distributed. The
      reorientation of TBAs was significant (p = 0.009), as was the provision of
      Motherpacks (p = .0001). The number of months that passed since the start of the
      intervention was also found to be significant (p = 0.033). The introduction of
      Motherpacks had the greatest effect on the outcome (0.2), followed by TBA
      intervention (0.15). Months since study start had a much lower effect (0.05).
      CONCLUSION: Collaborating with TBAs and offering basic commodities important to
      mothers and babies (Motherpacks) immediately after delivery at health facilities,
      can improve the uptake of health facility delivery services in poor rural
      communities that maintain a strong bias for TBA assisted home delivery.

PMID- 28431566
TI  - The prognostic value of the preoperative c-reactive protein/albumin ratio in
      ovarian cancer.
AB  - BACKGROUND: Inflammation plays an important role in the pathogenesis of ovarian
      cancer. This study sought to investigate the association between the preoperative
      c-reactive protein/albumin ratio (CRP/Alb) and oncological outcomes in ovarian
      cancer patients. METHODS: Two hundred patients with histologically verified
      ovarian cancer between June 2006 and July 2012 were retrospectively reviewed.
      Overall survival was evaluated by the Kaplan-Meier method and log-rank test. The
      significance of risk factors for overall survival was evaluated with the Cox
      proportional hazards model. Additionally, area under the receiver operating
      characteristic curve (AUC) was used to compare the predictive ability of CRP/Alb,
      Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil lymphocyte ratio
      (NLR), platelet lymphocyte ratio (PLR), prognostic index (PI) and prognostic
      nutritional index (PNI). RESULTS: The optimal cutoff value of CRP/Alb was 0.68.
      Increased CRP/Alb (>=0.68) was associated with advanced stage, residual tumor,
      ascites, elevated serum carbohydrate antigen(CA)-125 level, GPS, and mGPS (all p
      < 0.05). Patients with high CRP/Alb had poor overall survival compared to those
      with low CRP/Alb (p < 0.001). Multivariable analysis showed that CRP/Alb (Hazard
      Ratio (HR) 1.330, 95% confidence interval (CI) 1.131-1.564, p = 0.001), tumor
      stage (HR 1.577, 95% CI 1.189-2.091, p = 0.002), residual tumor (HR 2.337, 95% CI
      1.518-3.597, p < 0.001) and age (HR 1.017, 95% CI 1.000-1.035, p = 0.046) were
      independent prognostic factors for overall survival. Additionally, the CRP/Alb
      showed greater AUC values at 1 year (0.692), 3 years (0.659), and 5 years (0.682)
      than GPS, mGPS and PNI. CONCLUSIONS: The CRP/Alb is a novel independent marker of
      poor prognosis among ovarian cancer patients and shows superior prognostic
      ability compared to the established inflammation-based prognostic indices.

PMID- 28431567
TI  - Transcriptome profiling of Elymus sibiricus, an important forage grass in Qinghai
      Tibet plateau, reveals novel insights into candidate genes that potentially
      connected to seed shattering.
AB  - BACKGROUND: Elymus sibiricus is an important forage grass in semi-arid regions,
      but it is difficult to grow for commercial seed production due to high seed
      shattering. To better understand the underlying mechanism and explore the
      putative genes related to seed shattering, we conducted a combination of
      morphological, histological, physiochemical and transcriptome analysis on two E.
      sibiricus genotypes (XH09 and ZhN03) that have contrasting seed shattering.
      RESULTS: The results show that seed shattering is generally caused by a
      degradation of the abscission layer. Early degradation of abscission layers was
      associated with the increased seed shattering in high seed shattering genotype
      XH09. Two cell wall degrading enzymes, cellulase (CE) and polygalacturonase (PG),
      had different activity in the abscission zone, indicating their roles in
      differentiation of abscission layer. cDNA libraries from abscission zone tissue
      of XH09 and ZhN03 at 7 days, 21 days and 28 days after heading were constructed
      and sequenced. A total of 86,634 unigenes were annotated and 7110 differentially
      expressed transcripts (DETs) were predicted from "XH09-7 vs ZhN03-7", "XH09-21 vs
      ZhN03-21" and "XH09-28 vs ZhN03-28", corresponding to 2058 up-regulated and 5052
      down-regulated unigenes. The expression profiles of 10 candidate transcripts
      involved in cell wall-degrading enzymes, lignin biosynthesis and phytohormone
      activity were validated using quantitative real-time PCR (qRT-PCR), 8 of which
      were up-regulated in low seed shattering genotype ZhN03, suggesting these genes
      may be associated with reduction of seed shattering. CONCLUSIONS: The expression
      data generated in this study provides an important resource for future molecular
      biological research in E. sibiricus.

PMID- 28431568
TI  - A case report of severe calciphylaxis - suggested approach for diagnosis and
      treatment.
AB  - BACKGROUND: Calciphylaxis is a serious complication in patients with chronic
      kidney disease associated mineral and bone disorder. It can occur in conditions
      with low and high bone turnover. So far, there are no definite diagnostic and
      therapeutic guidelines which may prevent the devastating outcome in many
      calciphylaxis patients. We report a case which clearly illustrates that knowledge
      of the underlying bone disorder is essential for a directed treatment. Based on
      this experience we discuss a systematic diagnostic and therapeutic approach in
      patients with calciphylaxis. CASE PRESENTATION: We report a patient with severe
      calciphylaxis. Initial evaluation showed an elevated serum parathormone
      concentration and a bone-specific alkaline phosphatase activity in the upper
      normal range; however, the bone biopsy clearly showed adynamic bone disease.
      Extended dialysis with low calcium dialysate concentration and citrate
      anticoagulation, and administration of teriparatide led to a further increase in
      bone-specific alkaline phosphatase activity and most importantly, resulted in an
      activated bone turnover as confirmed by a second bone biopsy 11 weeks later.
      CONCLUSIONS: This case illustrates that laboratory tests cannot reliably
      differentiate between high and low bone turnover in calciphylaxis patients. More
      importantly, this case highlights the fact that specific therapies that alter
      bone metabolism cannot be applied without knowledge of the bone status. On this
      background, we suggest that bone biopsies should be an integral part in the
      diagnosis and therapeutic decision in these patients and should be evaluated in
      further studies.

PMID- 28431569
TI  - Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is
      associated with poorer health in cystic fibrosis patients: an Irish registry
      analysis.
AB  - BACKGROUND: Pulmonary infection is the main cause of death in cystic fibrosis
      (CF). Aspergillus fumigatus (AF) and Pseudomonas aeruginosa (PA) are the most
      prevalent fungal and bacterial pathogens isolated from the CF airway,
      respectively. Our aim was to determine the effect of different colonisation
      profiles of AF and PA on the clinical status of patients with CF. METHODS: A
      retrospective analysis of data from the Cystic Fibrosis Registry of Ireland from
      2013 was performed to determine the effect of intermittent and persistent
      colonisation with AF or PA or co-colonisation with both microorganisms on
      clinical outcome measures in patients with CF. Key outcomes measured included
      forced expiratory volume in one second (FEV1), number of hospitalisations,
      respiratory exacerbations and antimicrobials prescribed, and complications of CF,
      including CF related diabetes (CFRD) and allergic bronchopulmonary aspergillosis
      (ABPA). RESULTS: The prevalence of AF and PA colonisation were 11% (5%
      persistent, 6% intermittent) and 31% (19% persistent, 12% intermittent) in the
      Irish CF population, respectively. Co-colonisation with both pathogens was
      associated with a 13.8% reduction in FEV1 (p = 0.016), higher levels of
      exacerbations (p = 0.042), hospitalisations (p = 0.023) and antimicrobial usage
      (p = 0.014) compared to non-colonised patients and these clinical outcomes were
      comparable to those persistently colonised with PA. Intermittent and persistent
      AF colonisation were not associated with poorer clinical outcomes or ABPA.
      Patients with persistent PA had a higher prevalence of CFRD diagnosis (p =
      0.012). CONCLUSIONS: CF patients co-colonised with AF and PA had poor clinical
      outcomes comparable to patients persistently colonised with PA, emphasising the
      clinical significance of co-colonisation with these microorganisms.

PMID- 28431570
TI  - A relative quantitative Methylation-Sensitive Amplified Polymorphism (MSAP)
      method for the analysis of abiotic stress.
AB  - BACKGROUND: We present a new methylation-sensitive amplified polymorphism (MSAP)
      approach for the evaluation of relative quantitative characteristics such as
      demethylation, de novo methylation, and preservation of methylation status of
      CCGG sequences, which are recognized by the isoschizomers HpaII and MspI. We
      applied the technique to analyze aluminum (Al)-tolerant and non-tolerant control
      and Al-stressed inbred triticale lines. The approach is based on detailed
      analysis of events affecting HpaII and MspI restriction sites in control and
      stressed samples, and takes advantage of molecular marker profiles generated by
      EcoRI/HpaII and EcoRI/MspI MSAP platforms. METHODS: Five Al-tolerant and five non
      tolerant triticale lines were exposed to aluminum stress using the
      physiologicaltest. Total genomic DNA was isolated from root tips of all tolerant
      and non-tolerant lines before and after Al stress following metAFLP and MSAP
      approaches. Based on codes reflecting events affecting cytosines within a given
      restriction site recognized by HpaII and MspI in control and stressed samples
      demethylation (DM), de novo methylation (DNM), preservation of methylated sites
      (MSP), and preservation of nonmethylatedsites (NMSP) were evaluated. MSAP
      profiles were used for Agglomerative hierarchicalclustering (AHC) based on
      Squared Euclidean distance and Ward's Agglomeration method whereas MSAP
      characteristics for ANOVA. RESULTS: Relative quantitative MSAP analysis revealed
      that both Al-tolerant and non-tolerant triticale lines subjected to Al stress
      underwent demethylation, with demethylation of CG predominating over CHG. The
      rate of de novo methylation in the CG context was ~3-fold lower than
      demethylation, whereas de novo methylation of CHG was observed only in Al
      tolerant lines. CONCLUSIONS: Our relative quantitative MSAP approach, based on
      methylation events affecting cytosines within HpaII-MspI recognition sequences,
      was capable of quantifying de novo methylation, demethylation, methylation, and
      non-methylated status in control and stressed Al-tolerant and non-tolerant
      triticale inbred lines. The method could also be used to analyze methylation
      events affecting CG and CHG contexts, which were differentially methylated under
      Al stress. We cannot exclude that the methylation changes revealed among lines as
      well as between Al-tolerant and non-tolerant groups of lines were due to some
      experimental errors or that the number of lines was too small for ANOVA to prove
      the influence of Al stress. Nevertheless, we suspect that Al tolerance in
      triticale could be partly regulated by epigenetic factors acting at the level of
      DNA methylation. This method provides a valuable tool for studies of abiotic
      stresses in plants.

PMID- 28431571
TI  - Unique LCR variations among lineages of HPV16, 18 and 45 isolates from women with
      normal cervical cytology in Ghana.
AB  - BACKGROUND: In addition to being useful for classification, sequence variations
      of human Papillomavirus (HPV) genotypes have been implicated in differential
      oncogenic potential and a differential association with the different
      histological forms of invasive cervical cancer. These associations have also been
      indicated for HPV genotype lineages and sub-lineages. In order to better
      understand the potential implications of lineage variation in the occurrence of
      cervical cancers in Ghana, we studied the lineages of the three most prevalent
      HPV genotypes among women with normal cytology as baseline to further studies.
      METHODS: Of previously collected self- and health personnel-collected cervical
      specimen, 54, which were positive for HPV16, 18 and 45, were selected and the
      long control region (LCR) of each HPV genotype was separately amplified by a
      nested PCR. DNA sequences of 41 isolates obtained with the forward and reverse
      primers by Sanger sequencing were analysed. RESULTS: Nucleotide sequence
      variations of the HPV16 genotypes were observed at 30 positions within the LCR
      (7460 - 7840). Of these, 19 were the known variations for the lineages B and C
      (African lineages), while the other 11 positions had variations unique to the
      HPV16 isolates of this study. For the HPV18 isolates, the variations were at 35
      positions, 22 of which were known variations of Africa lineages and the other 13
      were unique variations observed for the isolates obtained in this study (at
      positions 7799 and 7813). HPV45 isolates had variations at 35 positions and 2
      (positions 7114 and 97) were unique to the isolates of this study. CONCLUSION:
      This study provides the first data on the lineages of HPV 16, 18 and 45 isolates
      from Ghana. Although the study did not obtain full genome sequence data for a
      comprehensive comparison with known lineages, these genotypes were predominately
      of the Africa lineages and had some unique sequence variations at positions that
      suggest potential oncogenic implications. These data will be useful for
      comparison with lineages of these genotypes from women with cervical lesion and
      all the forms of invasive cervical cancers.

PMID- 28431572
TI  - Hepatitis C virus NS4B protein induces epithelial-mesenchymal transition by
      upregulation of Snail.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection is an important cause of
      hepatocellular carcinoma (HCC). Epithelial to mesenchymal transition (EMT) is a
      key process associated with tumor metastasis and poor prognosis. HCV infection,
      HCV core and NS5A protein could induce EMT process, but the role of NS4B on EMT
      remains poorly understood. METHODS: We overexpressed HCV NS4B protein in HepG2
      cells or Huh7.5.1 cells infected by HCVcc, the E-cadherin expression, N-cadherin
      expression and the EMT-associated transcriptional factor Snail were determined.
      The migration and invasion capabilities of the transfected cells were evaluated
      using wound-healing assay. Additionally, we used Snail siRNA interference to
      confirm the relation of HCV NS4B and Snail on EMT promotion. RESULTS: HCV NS4B
      increased the expression of EMT related markers and promoted cell migration and
      invasion. Snail knock-down almost completely eliminated the function of NS4B
      protein in EMT changes and reversed cell migration capacity to lower level. HCV
      NS4B protein could reduce the expression of Scribble and Hippo signal pathway
      were subsequently inactivated, resulting in the activation of PI3K/AKT pathway,
      which may be the reason for the up-regulation of Snail. CONCLUSIONS: This study
      demonstrates that HCV NS4B protein induces EMT progression via the upregulation
      of Snail in HCC, which may be a novel underlying mechanism for HCV-associated HCC
      development, invasion and metastasis.

PMID- 28431573
TI  - A highly pathogenic simian/human immunodeficiency virus effectively produces
      infectious virions compared with a less pathogenic virus in cell culture.
AB  - BACKGROUND: The host range of human immunodeficiency virus (HIV) is quite narrow.
      Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of
      appropriate animal model systems. To overcome this, chimeric simian and human
      immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to
      macaques have been developed and used to investigate the pathogenicity of HIV-1
      in vivo. So far, we have many SHIV strains that show different pathogenesis in
      macaque experiments. However, dynamic aspects of SHIV infection have not been
      well understood. To fully understand the dynamic properties of SHIVs, we focused
      on two representative strains-the highly pathogenic SHIV, SHIV-KS661, and the
      less pathogenic SHIV, SHIV-#64-and measured the time-course of experimental data
      in cell culture. METHODS: We infected HSC-F with SHIV-KS661 and -#64 and measured
      the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F
      cells, the total viral load, and the infectious viral load daily for 9 days. The
      experiments were repeated at two different multiplicities of infection, and a
      previously developed mathematical model incorporating the infectious and non
      infectious viruses was fitted to the full dataset of each strain simultaneously
      to characterize the infection dynamics of these two strains. RESULTS AND
      CONCLUSIONS: We quantified virological indices including virus burst sizes and
      basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size
      of total and infectious viruses (viral RNA copies and TCID50, respectively), we
      found that there was a statistically significant difference between the
      infectious virus burst size of SHIV-KS661 and -#64, while there was no
      significant difference between the total virus burst size. Furthermore, our
      analyses showed that the fraction of infectious virus among the produced SHIV
      KS661 viruses, which is defined as the infectious viral load (TCID50/ml) divided
      by the total viral load (RNA copies/ml), is more than 10-fold higher than that of
      SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude
      that the highly pathogenic SHIV produces infectious virions more effectively than
      the less pathogenic SHIV in cell culture.

PMID- 28431574
TI  - Does where you live matter to your health? Investigating factors that influence
      the self-rated health of urban and rural Chinese residents: evidence drawn from
      Chinese General Social Survey data.
AB  - BACKGROUND: China's rapid urbanization over the past decades has exacerbated the
      problems of environmental degradation and health disparities. However, few
      studies have analysed the differences between urban and rural residents in
      relation to how environmental quality impacts health outcomes. This study
      examines the associations between Chinese people's perceptions of environmental
      quality and their self-rated health, particularly focusing on differences between
      rural and urban residents in environment-health relationships. METHODS: Using a
      logistic regression model and data from the 2013 Chinese General Social Survey
      (CGSS), a representative sample of data for 3,402 urban residents (46 +/- 16
      years) and 2,439 rural residents (48 +/- 15 years) was analysed. The dependent
      variable used for the logistic regressions was whether or not respondents
      reported being healthy. Independent variables included respondents' evaluations
      of the living environment, and how frequently they participated in physical
      activities. Interaction terms were employed to measure the moderating effects of
      physical exercise on the relationship between perceived environmental quality and
      health. RESULTS: The percentage of healthy urban residents was significantly
      larger than that of healthy rural respondents (70.87% versus 62.87%). Urban
      respondents living in areas with sufficient green space were more likely to
      report good health (OR = 0.749, CI = [0.628, 0.895]), while rural respondents
      without reliable access to fresh water were more likely to report poor health (OR
      = 0.762, CI = [0.612, 0.949]). Urban respondents who were exposed to green spaces
      and exercised frequently were 21.6 per cent more likely to report good health
      than those who exercised infrequently (OR = 1.216, CI = [1.047, 1.413]). Those
      who lived in areas with insufficient green space and exercised frequently were
      19.1 per cent less likely to report good health than those who exercised
      infrequently (OR = 0.805, CI = [0.469, 1.381]). No evidence suggested that
      physical exercise exerted a moderating effect on the relationship between
      exposure to air pollution and health. CONCLUSIONS: On average, urban residents
      have better health than rural residents. Among four indicators for low
      environmental quality (air pollution, lack of green spaces, water pollution,
      uncertain access to freshwater resources), green space was an important
      determinant of urban residents' health status, while unreliable access to fresh
      water harmed rural residents' health. Physical exercise moderated the effects of
      exposure to green spaces on urban residents' health.

PMID- 28431575
TI  - Heterogeneous ribonuclear protein A3 (hnRNP A3) is present in dipeptide repeat
      protein containing inclusions in Frontotemporal Lobar Degeneration and Motor
      Neurone disease associated with expansions in C9orf72 gene.
AB  - Frontotemporal Lobar Degeneration (FTLD) encompasses certain related
      neurodegenerative disorders which alter behaviour, personality and language.
      Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes
      in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP
      A1, A2/B1 and A3 was performed on sections of temporal cortex with hippocampus
      from 61 patients with FTLD, stratified by pathological hallmarks into FTLD-tau
      and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72
      expansions, MAPT or GRN mutations, or those without known mutation. Four patients
      with Motor Neurone Disease (MND) with C9orf72 expansions and 10 healthy controls
      were also studied. Semi-quantitative analysis assessed hnRNP staining intensity
      in dentate gyrus (DG) and CA4 region of hippocampus, and temporal cortex (Tcx) in
      the different pathological and genetic groups.Immunostaining for hnRNP A1, A2/B1
      and A3 revealed no consistent changes in pattern or amount of physiological
      staining across any of the pathological or genetic groups. No immunostaining of
      any inclusions resembling TDP-43 immunoreactive neuronal cytoplasmic inclusions
      or dystrophic neurites, was seen in either Tcx or DG of the hippocampus in any of
      the FTLD cases investigated for hnRNP A1, A2/B1 and A3. However, immunostaining
      for hnRNP A3 showed that inclusion bodies, resembling those TDP-43 negative, p62
      immunopositive structures containing dipeptide repeat proteins (DPR) were
      variably observed in hippocampus and cerebellum. The proportion of cases showing
      hnRNP A3-immunoreactive DPR, and the number of hnRNP A3-positive inclusions
      within cases, was significantly greater in DG than in cells of CA4 region and
      cerebellum, but the latter was significantly less in all three regions compared
      to that detected by p62 immunostaining.

PMID- 28431576
TI  - Enhanced neuroinvasion by smaller, soluble prions.
AB  - Infectious prion aggregates can propagate from extraneural sites into the brain
      with remarkable efficiency, likely transported via peripheral nerves. Yet not all
      prions spread into the brain, and the physical properties of a prion that is
      capable of transit within neurons remain unclear. We hypothesized that small,
      diffusible aggregates spread into the CNS via peripheral nerves. Here we used a
      structurally diverse panel of prion strains to analyze how the prion conformation
      impacts transit into the brain. Two prion strains form fibrils visible
      ultrastructurally in the brain in situ, whereas three strains form diffuse,
      subfibrillar prion deposits and no visible fibrils. The subfibrillar strains had
      significantly higher levels of soluble prion aggregates than the fibrillar
      strains. Primary neurons internalized both the subfibrillar and fibril-forming
      prion strains by macropinocytosis, and both strain types were transported from
      the axon terminal to the cell body in vitro. However in mice, only the
      predominantly soluble, subfibrillar prions, and not the fibrillar prions, were
      efficiently transported from the tongue to the brain. Sonicating a fibrillar
      prion strain increased the solubility and enabled prions to spread into the brain
      in mice, as evident by a 40% increase in the attack rate, indicating that an
      increase in smaller particles enhances prion neuroinvasion. Our data suggest that
      the small, highly soluble prion particles have a higher capacity for transport
      via nerves. These findings help explain how prions that predominantly assemble
      into subfibrillar states can more effectively traverse into and out of the CNS,
      and suggest that promoting fibril assembly may slow the neuron-to-neuron spread
      of protein aggregates.

PMID- 28431578
TI  - Is the effectiveness of patellofemoral bracing modified by patellofemoral
      alignment and trochlear morphology?
AB  - BACKGROUND: This study was performed to determine if the effectiveness of
      patellofemoral bracing as a treatment for patellofemoral osteoarthritis is
      influenced by patellofemoral joint alignment and trochlear morphology. We
      hypothesized that those with more extreme patellar malalignment would benefit
      more from bracing. METHODS: Thirty-eight patients who had received bracing as
      part of a comprehensive treatment plan for patellofemoral osteoarthritis were
      selected for this study. Ten measures of patellar alignment were taken from X
      rays. These alignment measures were divided into percentile groups (tertiles) for
      contingency table analysis. Treatment outcome was measured by Western Ontario and
      Macmasters Universities Osteoarthritis Index (WOMAC) scores and these were
      dichotomised into two groups according to "Improved" or "Not Improved" according
      to the minimum clinically important difference (MCID). Spearman's rho test was
      performed for continuous variables and Fisher's exact test was performed for
      correlation between tertile groups and MCID categories. RESULTS: Thirty-eight
      patients (9 male and 29 female) between the ages of 51 to 89 were included in
      this study. WOMAC scores ranged from -25 to 41.67, with a mean change of -3.97,
      31.6, 44.7 and 31.6% of patients falling into the "Improved" group for Global,
      Pain and Function scores respectively. We found a non-significant trend shown (p
      = 0.058, correlation coefficient 0.31) between bisect offset and change in WOMAC
      global, indicating a trend for higher change in WOMAC scores with increasing
      bisect offset. Statistically significant correlations were found between mean
      MCID categories for the WOMAC global and function groups when analysed against
      percentile groups for bisect offset (p < 0.01) and patellar subluxation distance
      (p < 0.05), indicating those in higher percentile groups were more likely not to
      improve after six months. CONCLUSION: Higher bisect offset and patellar
      subluxation distance measures were associated with poorer outcomes. However, due
      to the limited sample size, more studies are required to fully examine this
      relationship.

PMID- 28431577
TI  - Dichloroacetic acid-induced testicular toxicity in male rats and the protective
      effect of date fruit extract.
AB  - BACKGROUND: The present study was designed to investigate the protective effect
      of aqueous date extract (ADE) against the dichloroacetic acid (DCA)-induced
      testicular injury in rats. METHODS: Forty-eight male Wistar rats were randomly
      divided into six groups of eight: group I served as the control; group II was
      given ADE (4 ml/kg) by gavage; groups III and IV received DCA at 0.5 and 2 g/L
      drinking water, respectively; and groups V and VI received DCA at 0.5 and 2 g/L
      drinking water, respectively, before ADE administration. The experiment was
      performed for two months. RESULTS: Results showed that the absolute weights of
      testes and epididymis were decreased following the DCA administration. The
      testosterone, FSH and LH levels were also decreased. Severe histopathological
      changes in testes were observed including degeneration of seminiferous tubules
      and depletion of germ cells. These changes were associated with alterations of
      oxidative stress markers. Levels of lipid peroxidation and SOD and CAT activities
      were increased, while activity of GPx and GSH levels were decreased. Pretreatment
      with ADE has effectively alleviated the oxidative stress induced by DCA thereby
      restoring these parameters to normal values. CONCLUSIONS: These results suggest
      that ADE has a protective effect over DCA-induced oxidative damage in rat testes.

PMID- 28431579
TI  - Protocole of a controlled before-after evaluation of a national health
      information technology-based program to improve healthcare coordination and
      access to information.
AB  - BACKGROUND: Improvement of coordination of all health and social care actors in
      the patient pathways is an important issue in many countries. Health Information
      (HI) technology has been considered as a potentially effective answer to this
      issue. The French Health Ministry first funded the development of five TSN
      ("Territoire de Soins Numerique"/Digital health territories) projects, aiming at
      improving healthcare coordination and access to information for healthcare
      providers, patients and the population, and at improving healthcare professionals
      work organization. The French Health Ministry then launched a call for grant to
      fund one research project consisting in evaluating the TSN projects
      implementation and impact and in developing a model for HI technology evaluation.
      METHODS: EvaTSN is mainly based on a controlled before-after study design. Data
      collection covers three periods: before TSN program implementation, during early
      TSN program implementation and at late TSN program implementation, in the five
      TSN projects' territories and in five comparison territories. Three populations
      will be considered: "TSN-targeted people" (healthcare system users and people
      having characteristics targeted by the TSN projects), "TSN patient users" (people
      included in TSN experimentations or using particular services) and "TSN
      professional users" (healthcare professionals involved in TSN projects). Several
      samples will be made in each population depending on the objective, axis and
      stage of the study. Four types of data sources are considered: 1) extractions
      from the French National Heath Insurance Database (SNIIRAM) and the French
      Autonomy Personalized Allowance database, 2) Ad hoc surveys collecting
      information on knowledge of TSN projects, TSN program use, ease of use,
      satisfaction and understanding, TSN pathway experience and appropriateness of
      hospital admissions, 3) qualitative analyses using semi-directive interviews and
      focus groups and document analyses and 4) extractions of TSN implementation
      indicators from TSN program database. DISCUSSION: EvaTSN is a challenging French
      national project for the production of evidenced-based information on HI
      technologies impact and on the context and conditions of their effectiveness and
      efficiency. We will be able to support health care management in order to
      implement HI technologies. We will also be able to produce an evaluation toolkit
      for HI technology evaluation. TRIAL REGISTRATION: ClinicalTrials.gov ID:
      NCT02837406 , 08/18/2016.

PMID- 28431581
TI  - Sacroiliitis mimics: a case report and review of the literature.
AB  - BACKGROUND: Radiographic sacroiliitis is the hallmark of ankylosing spondylitis
      (AS), and detection of acute sacroiliitis is pivotal for early diagnosis of AS.
      Although radiographic sacroiliitis is a distinguishing feature of AS,
      sacroiliitis can be seen in a variety of other disease entities. CASE
      PRESENTATION: We present an interesting case of sacroiliitis in a patient with
      Paget disease; the patient presented with inflammatory back pain which was
      treated with bisphosphonate. This case demonstrates comorbidity with Paget
      disease and possible ankylosing spondylitis. We also present a review of the
      literature for other cases of Paget involvement of the sacroiliac joint.
      CONCLUSIONS: In addition, we review radiographic changes to the sacroiliac joint
      in classical ankylosing spondylitis as well as other common diseases. We compare
      and contrast features of other diseases that mimic sacroiliitis on a pelvic
      radiograph including Paget disease, osteitis condensans ilii, diffuse idiopathic
      skeletal hyperostosis, infections and sarcoid sacroiliitis. There are some
      features in the pelvic radiographic findings which help distinguish among mimics,
      however, one must also rely heavily on extra-pelvic radiographic lesions. In
      addition to the clinical presentation, various nuances may incline a clinician to
      the correct diagnosis; rheumatologists should be familiar with the imaging
      differences among these diseases and classic spondylitis findings.

PMID- 28431580
TI  - Cripto-1 acts as a functional marker of cancer stem-like cells and predicts
      prognosis of the patients in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is highly malignant with
      highly invasive and metastatic capabilities and poor prognosis. It is believed
      that the ESCC cancer stem-like cells (ECSLCs) are critical for tumorigenicity,
      invasion and metastasis of ESCC. However, the properties of ECSLCs vary with
      different markers used in isolation, so that new and more effective markers of
      ECSLCs need to be identified. This study aimed to estimate the potentiality of
      Cripto-1 (CR-1) as an ECSLC surface marker and investigate the clinical
      significance of CR-1 expression in ESCC. METHODS: ESCC cells with CR-1 high or CR
      1low were obtained by flow cytometry then their self-renewal capability and
      tumorigenicity were compared by colony and limiting dilution sphere formation
      analysis in vitro and xenograft in nude mice in vivo, respectively. Knockdown of
      CR-1 expression in ESCC cells was conducted with short hairpin RNA. Cell
      migration and invasion were examined by scratch test and matrigel transwell
      assay, respectively. Metastatic capability of ESCC cells was assayed by a mouse
      tail vein metastasis model. The levels of CR-1 expression in cancerous and paired
      adjacent normal tissues were assessed by IHC and qRT-RCR. RESULTS: CR-1high
      subpopulation of ESCC cells isolated by FACS expressed high level of genes
      related to stemness and epithelial-mesenchymal transition (EMT), and possessed
      high capacities of self-renewal, tumorigenesis, invasion and metastasis.
      Suppression of CR-1 expression significantly reduced the expression of stemness-
      and EMT-related genes and the capabilities of self-renewal in vitro,
      tumorigenicity and metastasis in vivo in ESCC cells. In the clinical ESCC
      specimens, the expression levels of CR-1 in cancerous tissues were positively
      correlated to TNM stage, invasive depth, and lymph node metastasis. Cox
      regression analysis indicated that CR-1 was an independent indicator of
      prognosis. The expression of CR-1 was found overlapping with aldehyde
      dehydrogenase 1A1 (ALDH1A1), an intracellular marker for ESCLCs, in ESCC cell
      lines and specimens. CONCLUSIONS: CR-1 is a functional and cell surface ECSLC
      marker, and an independent prognostic indicator as well as a potential
      therapeutic target for ESCC.

PMID- 28431582
TI  - Social media engagement analysis of U.S. Federal health agencies on Facebook.
AB  - BACKGROUND: It is becoming increasingly common for individuals and organizations
      to use social media platforms such as Facebook. These are being used for a wide
      variety of purposes including disseminating, discussing and seeking health
      related information. U.S. Federal health agencies are leveraging these platforms
      to 'engage' social media users to read, spread, promote and encourage health
      related discussions. However, different agencies and their communications get
      varying levels of engagement. In this study we use statistical models to identify
      factors that associate with engagement. METHODS: We analyze over 45,000 Facebook
      posts from 72 Facebook accounts belonging to 24 health agencies. Account usage,
      user activity, sentiment and content of these posts are studied. We use the
      hurdle regression model to identify factors associated with the level of
      engagement and Cox proportional hazards model to identify factors associated with
      duration of engagement. RESULTS: In our analysis we find that agencies and
      accounts vary widely in their usage of social media and activity they generate.
      Statistical analysis shows, for instance, that Facebook posts with more visual
      cues such as photos or videos or those which express positive sentiment generate
      more engagement. We further find that posts on certain topics such as occupation
      or organizations negatively affect the duration of engagement. CONCLUSIONS: We
      present the first comprehensive analyses of engagement with U.S. Federal health
      agencies on Facebook. In addition, we briefly compare and contrast findings from
      this study to our earlier study with similar focus but on Twitter to show the
      robustness of our methods.

PMID- 28431583
TI  - Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by
      targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer.
AB  - BACKGROUND: MicroRNAs are endogenously expressed, small non-coding RNAs that
      modulate gene expression by targeting specific mRNAs, resulting in translational
      repression or mRNA degradation. Although miR-584-5p has been reported to play a
      vital role in various malignancies, its role and the molecular mechanisms
      underlying the effects of miR-584-5p in gastric cancer (GC) remain to be
      clarified. In this study, we investigated the role of miR-584-5p in GC. METHODS:
      The expression of miR-584-5p and its specific target gene were determined in
      human GC specimens and cell lines by microRNA real-time polymerase chain reaction
      (RT-PCR), quantitative RT-PCR (qRT-PCR) and Western blot. The effects of miR-584
      5p depletion or ectopic expression on GC proliferation were evaluated in vitro
      using CCK-8 proliferation assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation,
      colony formation assays and cell-cycle assays and the in vivo effects were
      investigated using a mouse tumorigenicity model. Cell apoptosis was evaluated by
      in vitro flow cytometric analysis, cell viability assays and in vivo TUNEL
      assays. Luciferase reporter assays were employed to identify interactions between
      miR-584-5p and its specific target gene. RESULTS: A series of in vitro and in
      vivo gain- and loss-of-function assays revealed that miR-584-5p inhibited GC cell
      proliferation, while apoptosis was induced. Luciferase reporter assays and
      Western blot analysis revealed WWP1 to be a direct target of miR-584-5p. The
      effects of miR-584-5p-mimic were rescued by WWP1 overexpression. In contrast, the
      effects of the miR-584-5p-inhibitor were impaired by WWP1-shRNA. Furthermore, miR
      584-5p expression levels correlated negatively with WWP1 protein expression in GC
      tissues and GC cell lines. A series of investigations indicated that miR-584-5p
      promoted senescence and activated the TGFbeta signaling pathway by downregulation
      of WWP1. CONCLUSION: Taken together, these results suggest that downregulation of
      miR-584-5p contributes to tumor progression by downregulation of WWP1, thus,
      highlighting the potential of miR-584-5p as a therapeutic target for human GC.

PMID- 28431585
TI  - The utility of the basophil activation test in the diagnosis of immediate
      amoxicillin or amoxicillin-clavulanate hypersensitivity in children and adults.
AB  - BACKGROUND: The basophil activation test (BAT), has been proposed as a possible
      assay for the diagnosis of immediate-type allergy to beta-lactams (BLs). The aim
      of this study was to assess the utility of BAT in the diagnosis of amoxicillin
      (AMX) or AMX-clavulanate (AMX-C) IgE-mediated hypersensitivity in children and
      adults. MATERIAL AND METHODS: Eighteen children and 21 adults, with clinical
      history of immediate reactions to AMX or AMX-C, were referred to Anna Meyer
      Children's Hospital and San Giovanni di Dio Hospital, respectively. They
      underwent in vivo tests (skin prick test and intradermal test). Moreover, BAT
      with AMX or AMX-C was performed within 6 months from the reaction. RESULTS: In
      the pediatric group, the concordance between the skin tests (ST) and BAT results
      was 83.3%. Upon comparing the symptom grades and ST results to the BAT results,
      we found that the reaction severity and ST positivity did not correlate with BAT
      results in children. In the adult group, the concordance between the ST and BAT
      results was 61.9%. Upon comparing patients with severe reactions and patients
      with mild reactions in terms of BAT results, we found a BAT sensitivity of 38.5%
      and a specificity of 100%. When comparing the symptom grades to the BAT results,
      we found that no patients with mild symptoms had a positive BAT result, whereas
      38.5% of patients with severe symptoms had a positive BAT result. CONCLUSIONS:
      BAT does not seem to be a useful tool to increase the sensitivity of an allergy
      work-up to diagnose immediate hypersensitivity to AMX or AMX-C.

PMID- 28431586
TI  - Expression of calcitonin gene-related peptide in the infrapatellar fat pad in
      knee osteoarthritis patients.
AB  - BACKGROUND: The infrapatellar fat pad (IPFP) has been implicated as a possible
      source of osteoarthritis (OA) development and knee pain due to the production of
      inflammatory mediators and the existence of nerve fibers within this structure.
      Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that is
      localized to joint tissues and has recently been implicated in the development of
      knee OA and OA pain. To date, however, the expression levels of CGRP in the IPFP
      of human knee OA patients have not been examined. METHODS: IFFP and synovial
      (SYN) tissues were harvested from 100 individuals with radiographic knee OA
      (unilateral Kellgren/Lawrence [K/L] grades 2-4) during total knee arthroplasty
      and subjected to immunohistochemical analysis for CGRP localization. In addition,
      the messenger RNA (mRNA) expression levels of CGRP and cyclooxygenase-2 (COX-2)
      in the collected tissues were evaluated and compared using real-time PCR analysis
      of total RNA extracts. CGRP and COX-2 mRNA expression were also compared among
      individuals with K/L grades 2-4. RESULTS: CGRP-positive cells were detected in
      the capillaries within the IPFP and lining layer of SYN tissue. The expression
      levels of CGRP in the IPFP were positively correlated with COX-2 and were
      significantly higher than those in SYN tissue. CGRP expression in tissue from the
      KL4 group was twofold higher than that from the KL2 group. CONCLUSIONS: The IPFP
      of knee OA patients produces relatively high levels of CGRP, which may be
      regulated by COX-2 at the transcriptional level. Further studies are needed to
      determine if CGRP levels are directly linked to OA pathology.

PMID- 28431587
TI  - Psychometric properties of the SDM-Q-9 questionnaire for shared decision-making
      in multiple sclerosis: item response theory modelling and confirmatory factor
      analysis.
AB  - BACKGROUND: Shared decision-making is a cornerstone of patient-centred care. The
      9-item Shared Decision-Making Questionnaire (SDM-Q-9) is a brief self-assessment
      tool for measuring patients' perceived level of involvement in decision-making
      related to their own treatment and care. Information related to the psychometric
      properties of the SDM-Q-9 for multiple sclerosis (MS) patients is limited. The
      objective of this study was to assess the performance of the items composing the
      SDM-Q-9 and its dimensional structure in patients with relapsing-remitting MS.
      METHODS: A non-interventional, cross-sectional study in adult patients with
      relapsing-remitting MS was conducted in 17 MS units throughout Spain. A
      nonparametric item response theory (IRT) analysis was used to assess the latent
      construct and dimensional structure underlying the observed responses. A
      parametric IRT model, General Partial Credit Model, was fitted to obtain
      estimates of the relationship between the latent construct and item
      characteristics. The unidimensionality of the SDM-Q-9 instrument was assessed by
      confirmatory factor analysis. RESULTS: A total of 221 patients were studied (mean
      age = 42.1 +/- 9.9 years, 68.3% female). Median Expanded Disability Status Scale
      score was 2.5 +/- 1.5. Most patients reported taking part in each step of the
      decision-making process. Internal reliability of the instrument was high
      (Cronbach's alpha = 0.91) and the overall scale scalability score was 0.57,
      indicative of a strong scale. All items, except for the item 1, showed
      scalability indices higher than 0.30. Four items (items 6 through to 9) conveyed
      more than half of the SDM-Q-9 overall information (67.3%). The SDM-Q-9 was a good
      fit for a unidimensional latent structure (comparative fit index = 0.98, root
      mean-square error of approximation = 0.07). All freely estimated parameters were
      statistically significant (P < 0.001). All items presented standardized parameter
      estimates with salient loadings (>0.40) with the exception of item 1 which
      presented the lowest loading (0.26). Items 6 through to 8 were the most relevant
      items for shared decision-making. CONCLUSIONS: The SDM-Q-9 presents appropriate
      psychometric properties and is therefore useful for assessing different aspects
      of shared decision-making in patients with multiple sclerosis.

PMID- 28431588
TI  - CHIVA - A prospective study of a vein sparing technique for the management of
      varicose vein disease.
AB  - BACKGROUND: Varicose vein disease (VVD) affects approximately one third of
      adults. Cure Conservatrice et Hemodynamique de l'Insuffisance Veineuse en
      Ambulatoire (CHIVA) is a minimally invasive, vein sparing technique that is
      emerging as an alternative to ablative techniques for treating VVD. METHODS: This
      prospective study assessed the rate of recurrence of venous reflux with CHIVA. We
      evaluated 150 primary procedures with clinical and duplex ultrasound examinations
      pre and post operatively. Patients were followed at <3 months and >1-year post
      op. Recurrence was defined as reflux in the diseased vessel at the saphenofemoral
      junction on duplex examination. RESULTS: There was no documented recurrence at
      the early follow up. To date, 58 legs have completed the late follow up and
      reflux was found in 5 legs resulting in a recurrence rate of 8.6%; 95% CI (2.4%,
      19%). CONCLUSION: Our results indicate that CHIVA appears to offer a promising
      alternative for the treatment of VVD.

PMID- 28431584
TI  - Monitoring quality and coverage of harm reduction services for people who use
      drugs: a consensus study.
AB  - BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for
      people who use drugs over the last decades globally, coverage remains poor in
      most countries, while quality is often unknown. This paper aims to discuss the
      historical development of successful epidemiological indicators and to present a
      framework for extending them with additional indicators of coverage and quality
      of harm reduction services, for monitoring and evaluation at international,
      national or subnational levels. The ultimate aim is to improve these services in
      order to reduce health and social problems among people who use drugs, such as
      human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime
      and legal problems, overdose (death) and other morbidity and mortality. METHODS
      AND RESULTS: The framework was developed collaboratively using consensus methods
      involving nominal group meetings, review of existing quality standards, repeated
      email commenting rounds and qualitative analysis of opinions/experiences from a
      broad range of professionals/experts, including members of civil society and
      organisations representing people who use drugs. Twelve priority candidate
      indicators are proposed for opioid agonist therapy (OAT), needle and syringe
      programmes (NSP) and generic cross-cutting aspects of harm reduction (and
      potentially other drug) services. Under the specific OAT indicators, priority
      indicators included 'coverage', 'waiting list time', 'dosage' and 'availability
      in prisons'. For the specific NSP indicators, the priority indicators included
      'coverage', 'number of needles/syringes distributed/collected', 'provision of
      other drug use paraphernalia' and 'availability in prisons'. Among the generic or
      cross-cutting indicators the priority indicators were 'infectious diseases
      counselling and care', 'take away naloxone', 'information on safe use/sex' and
      'condoms'. We discuss conditions for the successful development of the suggested
      indicators and constraints (e.g. funding, ideology). We propose conducting a
      pilot study to test the feasibility and applicability of the proposed indicators
      before their scaling up and routine implementation, to evaluate their
      effectiveness in comparing service coverage and quality across countries.
      CONCLUSIONS: The establishment of an improved set of validated and
      internationally agreed upon best practice indicators for monitoring harm
      reduction service will provide a structural basis for public health and
      epidemiological studies and support evidence and human rights-based health
      policies, services and interventions.

PMID- 28431589
TI  - T2 relaxometry helps prognosticate seizure outcome in patients with solitary
      cerebral cysticercosis.
AB  - OBJECTIVE: Correlate serial T2 relaxometry (T2R) values with long term seizure
      outcome in patients with solitary cerebral cysticercosis (SCC) in order to
      establish its usefulness as a prognostic marker in these patients. METHODS:
      Patients with new-onset seizures due to SCC were imaged serially using a pre
      determined MRI protocol at enrolment and after 3, 6, 12 and 24months. T2
      relaxometry was performed using a dual echo sequence with maps generated manually
      from the measured image intensities at the level of the lesion. Patients were
      randomised to receive albendazole plus antiepileptic drugs, or only antiepileptic
      treatment ("controls"). At each visit, as well as four years after study
      initiation, patients were reviewed for seizure recurrence. Clinical and
      radiological outcomes were assessed by physicians blinded to treatment received.
      RESULTS: Of 123 patients recruited, 77 had at least four MRIs and >12month follow
      up, and were included for analysis. Baseline clinical and demographic parameters
      as well as antiepileptic treatment were similar between albendazole and control
      groups. T2 values from the lesion were higher than normal parenchyma initially,
      and fell to approach normal over six months. Controls had higher T2 values from
      the lesion centre and wall at six months than those who received albendazole.
      However no difference was seen in T2 values from perilesional parenchyma between
      treatment and control groups, indicating lack of modulation of the development of
      perilesional gliosis by albendazole therapy. Patients with seizures persisting
      >6months after enrolment had higher perilesional T2 values than those who were
      seizure-free. A rise in perilesional T2 value at 12months is probably due to
      gliosis. A later stage of degeneration was associated with a reduced likelihood
      of seizure relapse. SIGNIFICANCE: T2 relaxometry at three and six months after
      seizure onset can identify patients likely to have seizures beyond six months
      after onset. Persistently abnormal T2 values in patients with poorer outcomes
      reflect the development of perilesional gliosis.

PMID- 28431590
TI  - Delays in door-to-needle time for acute ischemic stroke in the emergency
      department: A comprehensive stroke center experience.
AB  - BACKGROUND: Current American Stroke Association guidelines recommend initiating
      intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) within 60min of
      patient arrival, given the benefits of IVT for AIS are time dependent. This study
      aimed to identify the delaying factors in door-to-needle time (DTN) in the
      emergency department of one of the largest comprehensive stroke centers in New
      York State. We also recommended measures to reduce the delays. METHODS: We
      retrospectively reviewed the medical charts of all AIS patients who received IVT
      in our emergency department patients between April 1, 2012 and December 31, 2015
      to identify those with a DTN time of >60min. We categorized the factors causing
      the delay into different groups. For each group, we recommended measures to
      reduce the treatment delays. RESULTS: A total of 487 patients received IVT for
      AIS during the 3.7-year period. Of these, 96 patients (20.4%) met our DTN time
      delay criteria. Delays for obtaining stroke imaging and hypertension control were
      the most common factors. Thirty eight patients (39.5%) had delay in obtaining CT
      based stroke imaging. Twenty-two patients (22.9%) required control of elevated
      blood pressure prior to IVT. Other causes for delay in DTN time included delay in
      stroke triage and paging (11.4%), fluctuating neurological symptoms (7.2%),
      uncertainty about diagnosis (12.5%), delays associated with obtaining consent
      (9.3%), and uncertainty about the time of symptom onset (5.2%). CONCLUSION:
      Important and common causes of delay in IVT for AIS were identified in a review
      of charts at our comprehensive stroke center. The authors recommend strategies to
      achieve faster DTN time for each of the delaying factor categories including
      faster acquisition and interpretation of stroke imaging, more effective triage
      protocols and faster blood pressure control for AIS patients who are eligible for
      IVT.

PMID- 28431591
TI  - Saccadic hypermetria on abduction of the ipsilesional eye in internuclear
      ophthalmoplegia.

PMID- 28431592
TI  - Facial diplegia resembling bilateral Ramsay Hunt Syndrome.

PMID- 28431593
TI  - High on treatment platelet reactivity to aspirin and clopidogrel in ischemic
      stroke: A systematic review and meta-analysis.
AB  - Emerging studies highlight high on-treatment of platelet reactivity (HTPR) as a
      major hindrance to the secondary prevention of cardiovascular ischemic events.
      The aim of this systematic review and meta-analysis is to assess the prevalence
      of HTPR in patients with ischemic stroke (IS) or transient ischemic attack (TIA)
      and reveal a possible relation with a higher risk of cerebrovascular event
      recurrence. Studies were selected if they reported absolute numbers or
      percentages of HTPR with ASA or clopidogrel in IS/TIA patients at any time point
      after the cerebrovascular event onset and assessed with any type of platelet
      function tests. We included 52 full-text studies with a total of 8364 patients.
      Overall, the pooled prevalence of HTPR was 24% (95%CI: 20-27%). In subgroup
      analyses, the prevalence of HTPR on ASA was 23% (95%CI: 20-28%), on clopidogrel
      27% (95%CI: 22-32%) and on dual antiplatelet treatment (DAPT) 7% (95%CI: 5-10%).
      The overall analysis of all studies providing data on the risk of IS/TIA
      recurrence, indicates that the patients with HTPR had a significantly higher risk
      for IS/TIA recurrence (RR=1.81, 95%CI: 1.30-2.52; p<0.001). In conclusion the
      present study shows a significant lower prevalence of HTPR in DAPT and an
      increased rate of recurrent cerebrovascular ischemic events in patients
      presenting HTPR.

PMID- 28431594
TI  - Phenotypic spectrum of DARS2 mutations.

PMID- 28431595
TI  - Novel missense variant of CACNA1A gene: A case report of a family with episodic
      ataxia type 2.

PMID- 28431596
TI  - Hemiageusia caused by ipsilateral rostral midbrain infarction.

PMID- 28431597
TI  - Cefepime-induced encephalopathy in end-stage renal disease patients.
AB  - OBJECTIVES: Impaired renal function is a risk factor for cefepime (CFPM)-induced
      encephalopathy (CFPMIE) in patients treated with CFPM; dose-titration to renal
      function is recommended to prevent CFPMIE. However, available evidence on the
      incidence of CFPMIE or preventive efficacy of dose adjustment against CFPMIE in
      end-stage renal disease (ESRD) patients is limited. METHODS: Single-centre,
      retrospective observational study. We reviewed consecutive in-hospital adult
      patients treated with adjusted-dose of CFPM in the period between September 2012
      and September 2016, and assessed the CFPMIE in ESRD patients treated with
      adjusted-dose of CFPM. RESULTS: Out of 422 eligible patients, 6 patients (1.4%)
      were diagnosed with CFPMIE. The incidence of CFPMIE in ESRD patients was 7.5%
      (5/67). Among ESRD patients, pre-existing central nervous system (CNS) morbidity
      was significantly associated with the risk of CFPMIE. CFPMIE occurred in ESRD
      patients regardless of daily dose, and even with 0.5g/day of CFPM. CONCLUSIONS:
      Pre-existing CNS morbidity may be associated with an increased risk of CFPMIE in
      ESRD patients. No significant association was observed between CFPM dose and
      incidence of CFPMIE in ESRD patients, and future investigation on the safer dose
      adjustment strategy in ESRD patients is required for achieving balance between
      successful infectious treatment and reducing CFPMIE.

PMID- 28431598
TI  - Apraclonidine in the treatment of ptosis.
AB  - Transient ptosis is a known complication of botulinum toxin (BoNT) injection due
      to inadvertent migration of toxin into the levator palpebrae superioris muscle.
      Currently there is no treatment available for BoNT induced ptosis. Apraclonidine
      hydrochloride is a topical ophthalmic solution with selective alpha-2 and weak
      alpha-1 receptor agonist activity that has the ability to elevate the eye lid.
      Apraclonidine has been used as a diagnostic test in Horner's syndrome. We
      evaluated the effects apraclonidine in a cohort of BoNT induced ptosis and a
      patient with Horner syndrome. Each patient was administered 2 drops of
      apraclonidine 0.5% solution to the eye with the ptosis and was re-examined 20
      30min later. All 6 patients showed improvement in ptosis. There was also
      improvement in ptosis in a patient with Horner's syndrome. Apraclonidine is not
      only useful as a diagnostic test in Horner's syndrome, but may be an effective
      and safe treatment for BoNT-induced ptosis.

PMID- 28431599
TI  - Usefulness of Ilae 2010 classification in Mexican epilepsy patients.
AB  - OBJECTIVE: Advances in neuroimaging, genomics, and molecular biology have
      improved the understanding of the pathogenesis of epilepsy. That is why the
      International League Against Epilepsy (ILAE) has created a new classification
      system. The present study aims to evaluate the association between epilepsy cases
      classified by the ILAE 2010 classification proposal, electroencephalography
      (EEG), and magnetic resonance imaging brain findings (MRI). METHODS: Prospective
      cross-sectional design of 277 cases of epilepsy seen at the Epilepsy Clinic,
      Hospital Central "Dr. Ignacio Morones Prieto", were compared with the ILAE
      classification based on the etiology and clinical manifestations and their MRI
      and EEG findings. STATISTICAL ANALYSIS: Cochran, Mantell, Haenzel test with
      significance p<0.05. RESULTS: MRI findings were associated with the etiology of
      the ILAE classification. According to EEG findings, the structural-metabolic
      etiology patients had more dysfunctional reports than genetic or unknown etiology
      patients (p<0.05). SIGNIFICANCE: The adoption of the ILAE classification is
      recommended, as it can provide useful guidance towards the etiology of cases of
      epilepsy even when brain MRIs and EEGs are not available.

PMID- 28431600
TI  - Assessment of 'on-treatment platelet reactivity' and relationship with cerebral
      micro-embolic signals in asymptomatic and symptomatic carotid stenosis.
AB  - INTRODUCTION: The relationship between on-treatment platelet reactivity and
      cerebral micro-embolic signals (MES) is unknown, and has not been previously
      simultaneously assessed in asymptomatic and symptomatic carotid stenosis
      patients. METHODS: Consecutive eligible patients with >=50% asymptomatic or
      recently symptomatic carotid stenosis (<=4weeks following TIA/ischaemic stroke)
      were recruited to this pilot study. Symptomatic patients were followed up to the
      'late' phase (>=3months) following symptom onset or carotid intervention;
      longitudinal data were analysed from symptomatic patients with data available at
      both time-points. Platelet function/reactivity was assessed with the PFA-100(r)
      to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in
      citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial
      Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed
      to classify patients as MES +ve or MES -ve. RESULTS: 31 patients with >=50%
      asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were
      included. 35 symptomatic patients were followed up to the late phase (23
      following carotid intervention). Prevalence of 'high on-treatment platelet
      reactivity' (HTPR) on the C-EPI cartridge did not differ between asymptomatic and
      symptomatic patients overall, but was lower in 'symptomatic post-intervention'
      than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p=0.03). The
      prevalence of HTPR on the C-EPI cartridge decreased between the early and late
      phases in symptomatic patients (63% vs. 34%; p=0.017), including those on aspirin
      monotherapy (p=0.016). There were no significant differences in HTPR status
      between asymptomatic vs. early or late symptomatic MES +ve or MES -ve patients.
      DISCUSSION: Carotid interventional treatment, presumably in combination with
      resolution of the acute phase response, may decrease the prevalence of HTPR in
      patients with recently symptomatic carotid stenosis over time. Preliminary
      subgroup analysis suggests that successful intervention may reduce the prevalence
      of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic
      medically-treated patients on aspirin monotherapy. Larger, longitudinal studies
      are warranted to reassess the impact of more intensive secondary preventive
      treatment on ex vivo platelet function at different levels of shear stress in
      carotid stenosis patients.

PMID- 28431601
TI  - Gelastic seizures caused by subtle focal cortical dysplasia in the inferior
      frontal gyrus: Three case reports.

PMID- 28431602
TI  - A comprehensive analysis of the relationship between ACA velocities and ACA
      infarction following aneurysmal subarachnoid hemorrhage.
AB  - PURPOSE: To evaluate the relationship between anterior cerebral artery (ACA)
      velocities (and ancillary parameters) and ACA infarction following aneurysmal
      subarachnoid hemorrhage (aSAH), and to examine the factors that influence
      velocities. METHODS: Retrospective investigation of 500 consecutive aSAH
      patients. ACA mean velocities (Vm) were evaluated by daily transcranial
      ultrasound during the early (days 1-4) and late (days 5-20) periods
      posthemorrhage. Presence and timing of acute ACA infarctions were identified by
      serial retrospective review of cerebral computerized tomography (CT) scans.
      Predictors of ACA velocities were identified and compared to predictors of
      vasospasm and infarction from the literature. RESULTS: Decreased velocities on
      the day of infarction were observed in infarct-positive vessels when compared to
      infarct-negative vessels. ACA velocity increases, ipsilateral/contralateral ACA
      velocity ratios, and ACA velocity ranges, were inaccurate in anticipating
      infarction. Decreased ACA index velocities were moderately accurate in
      anticipating ACA infarction during the early [Vm<60cms/s], late [Vm<70cms/s] and
      overall [Vm<70cms/s] time periods. Decreased index velocities also independently
      predicted infarction during all time periods. ACA velocities were most
      consistently predicted by age, race, hemorrhage quantity on CT, and ACA/ACom
      (anterior communicating artery) aneurysm location. CONCLUSIONS: ACA velocity
      increases and ancillary parameters do not relate to the development of
      infarction, whereas velocity decreases are moderately accurate in anticipating
      infarction. Predictors of velocity increases generally coincide with those of
      vasospasm, whereas predictors of velocity decreases coincide more with those of
      infarction following aSAH.

PMID- 28431603
TI  - Extending the aceruloplasminemia phenotype: NBIA on imaging and acanthocytosis,
      yet only minor neurological findings.

PMID- 28431604
TI  - A reappraisal of diagnostic tests for myasthenia gravis in a large Asian cohort.
AB  - BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease
      characterized by weakness of bodily skeletal muscles. Office-based diagnostic
      tests such as repetitive nerve stimulation (RNS), single fiber electromyography
      (SFEMG), and the ice test, are used to refine the differential clinical diagnosis
      of this disease. Evaluating the clinical sensitivity and specificity of these
      tests, however, may be confounded by lack of a gold standard, non-blinding,
      incorporation bias, use of non-representative populations and retrospective data.
      OBJECTIVE: In this study comprising a large Asian cohort of 127 patients
      recruited from a Neuro-ophthalmology clinic, we minimized aforementioned
      confounders and tested the diagnostic value of 3 office-based tests against 2
      reference standards of MG by virtue of clinical features, antibody assay and
      response to treatment. RESULTS: Regardless of the reference standard used, the
      ice and SFEMG tests displayed a higher sensitivity (86.0 to 97.3%) compared to
      the RNS test (21.3 to 30.6%). Conversely, the specificity of the ice (31.3%) and
      SFEMG (21.7% and 17.2%) tests were reduced compared to the RNS test (82.6% and
      84.4%). The combined use of the ice test and SFEMG, improved the specificity of
      MG diagnosis to 63.6% and 64.3%, without affecting the sensitivity of those
      tests. CONCLUSION: Our findings indicate, in an Asian population, high
      sensitivity of the SFEMG test and suggest the ice test as a valid, affordable and
      less technically demanding approach to diagnose MG with ocular involvement. Both
      ice test and SFEMG alone, however, yielded poor specificity. We suggest that the
      combination of SFEMG and ice test provides a more reliable diagnosis of MG.

PMID- 28431605
TI  - Global brain atrophy and metabolic dysfunction in LGI1 encephalitis: A
      prospective multimodal MRI study.
AB  - BACKGROUND: Chronic cognitive deficits are frequent in leucin-rich glioma
      inactivated 1 protein (LGI1) encephalitis. We examined structural and metabolic
      brain abnormalities following LGI1 encephalitis and correlated findings with
      acute and follow-up clinical outcomes. METHODS: Nine patients underwent
      prospective multimodal 3 Tesla MRI 33.1+/-18months after disease onset, including
      automated volumetry, diffusion tensor imaging (DTI) and magnetic resonance
      spectroscopy (MRS). Data were compared to 9 age- and sex-matched healthy
      controls. RESULTS: Although extratemporal lesions were not present on MRI in the
      acute stage, tract-based spatial statistics analyses of DTI during follow-up
      showed widespread changes in the cerebral and cerebellar white matter (WM), most
      prominent in the anterior parts of the corona radiata, capsula interna and corpus
      callosum. MRS revealed lower glutamine/glutamate WM levels compared to controls.
      Higher cerebellar gray matter volume was associated with better function at
      disease onset (measured by the modified Rankin Scale), and higher putaminal
      volume was associated with better cognition by Addenbrooke's Cognitive
      Examination test at 23.4+/-7.6months. CONCLUSIONS: Poor clinical outcome
      following LGI1 encephalitis is associated with global brain atrophy and
      disintegration of white matter tracts. The pathological changes affect not only
      temporomesial structures but also frontal lobes and the cerebellum.

PMID- 28431606
TI  - Screening for cognitive and behavioural impairment in amyotrophic lateral
      sclerosis: Frequency of abnormality and effect on survival.
AB  - OBJECTIVE: To screen for cognitive and behavioural impairment in people with
      amyotrophic lateral sclerosis (ALS) and controls with neuromuscular disease and
      to correlate these with clinical features. METHODS: 108 people with ALS and 60
      controls with other neuromuscular diseases were recruited and assessed with the
      Addenbrooke's cognitive examination-III (ACE-III), the frontal assessment battery
      (FAB), and the executive function component of the Edinburgh cognitive and
      behavioural ALS screen (ECAS). The Amyotrophic lateral sclerosis-Frontotemporal
      dementia questionnaire (ALS-FTD-Q) and the Motor Neuron Disease Behavioural
      instrument (MiND-B) were administered to the caregivers of people with ALS. The
      prevalence of abnormalities was determined and correlated with clinical features
      and survival. In 37 people with ALS, serial studies were performed. RESULTS: The
      frequencies of cognitive impairment based on the ACE-III and FAB were 30.0% and
      14.0%, in ALS and 11.7% and 3.3% in controls, respectively. Age and years of
      education influence the results of the ACE-III and ECAS executive function. In
      ALS, the frequencies of behavioural impairment based on ALS-FTD-Q and MiND-B were
      32.1% and 39.4%, respectively. There is significant correlation of ALS-FTD-Q and
      MiND-B with the ALSFRS-R score. ALS participants with cognitive impairment
      measured with ACE-III had significantly shorter survival time than those without.
      ALS participants with behavioural impairment measured with ALS-FTD-Q had worse
      prognosis than those without. No significant difference was found between the
      first two serial cognitive tests based on ACE-III and FAB by using generalized
      estimating equation. CONCLUSION: There is a greater frequency of cognitive
      impairment in people with ALS than in patients with other neuromuscular diseases.
      The cognitive and behavioural tests are potential biomarkers of the prognosis of
      ALS. The results of cognitive tests are stable over 6months and possibly longer.

PMID- 28431607
TI  - Sigma-1 receptor in brain ischemia/reperfusion: Possible role in the NR2A-induced
      pathway to regulate brain-derived neurotrophic factor.
AB  - Sigma-1 receptor (sigma1r) activation could attenuate the learning and memory
      deficits in the AD model, ischemia model and others. In our previous study, the
      activation of sigma1r increased the expression of brain-derived neurotrophic
      factor (BDNF), possibly through the NR2A-induced pathway, and sigma1r agonists
      might function as neuroprotectant agents in vascular dementia. Here, we used
      sigma1r knockout mice to confirm the role of sigma1r. Furthermore, an antagonist
      of NR2A was first used to investigate whether the NR2A-induced pathway is the
      necessary link between sigma1r and BDNF. The operation of brain
      ischemia/reperfusion was induced by bilateral common carotid artery occlusion for
      20min in C57BL/6 and sigma1r knockout mice as the ischemic group. A sigma1r
      agonist, PRE084 (1mg/kg, i.p.), and NR2A antagonist, PEAQX (10mg/kg, i.p.), were
      administered once daily throughout the experiment. Behavioral tests were
      performed starting on day 8. On day 22 after brain ischemia/reperfusion, mice
      were sacrificed and brains were immediately collected and the injured and the
      hippocampus was isolated and stored at -80 degrees C for western blot analysis.
      After ischemic operation, contrast with the sigma1r knockout mice, PRE084
      significantly ameliorated learning and memory impairments in the behavioral
      evaluation, and prevented the protein decline of BDNF, NR2A, CaMKIV and TORC1
      expression in wild-type mice. However, the effects of PRE084 on CaMKIV-TORC1-CREB
      and BDNF, even for learning and memory impairment, were antagonized by the co
      administration of PEAQX, an antagonist of NR2A. The activation of sigma1r
      improves the impairment of learning and memory in the ischemia/reperfusion model,
      and the expression of BDNF, which may have been achieved through the NR2A-CaMKIV
      TORC1 pathway.

PMID- 28431608
TI  - Relationship between serum uric acid and ischemic stroke in a large type 2
      diabetes population in China: A cross-sectional study.
AB  - OBJECTIVE: To investigate the relationship of serum UA and ischemic stroke in
      type 2 diabetes patients in China. METHOD: We examined the above relationship
      using the data of the project "Comprehensive Research on the Prevention and
      Control of the Diabetes" (CRPCD) study. A total of 19,442 participants were
      enrolled in the cross-sectional study. The enrolled participants were divided
      into quintiles of the serum UA levels with cut off values for two age groups (<60
      versus >=60years). Binary logistic regression analyses were used to evaluate
      whether the levels of serum UA were independently associated with ischemic stroke
      in type 2 diabetes. RESULTS: The serum UA levels were significantly higher in the
      participants with age>=60years than those with age<60years (P=0.000). In the age
      group of <60years, the odds ratio for ischemic stroke with type 2 diabetes in
      quintile 5 over quintile 1 was 2.420 (95% CI, 1.566-3.470) in the unadjusted
      model and 1.765 (95% CI, 1.097-2.840) after controlling potential confounders.
      However, the reverse results were observed in the age group of >=60years. The
      odds ratio in quintile 4 over quintile 1 in model 3 and model 4 were 0.767 (95%
      CI, 0.630-0.934) and 0.782 (95% CI, 0.640-0.957). CONCLUSION: Our results
      indicated that serum UA levels were independently positively associated with
      ischemic stroke in patients aged <60years, but the association was U-shaped in
      patients aged >=60years.

PMID- 28431609
TI  - Benefit-risk perception of natalizumab therapy in neurologists and a large cohort
      of multiple sclerosis patients.
AB  - BACKGROUND: Natalizumab (NAT) is associated with the risk of progressive
      multifocal leukoencephalopathy (PML). Risk stratification algorithms have been
      developed, however, without detectable reduction of PML incidence. OBJECTIVE: To
      evaluate to which extent patients and physicians understand and accept risks
      associated with NAT treatment. METHODS: Prospective observational cohort study in
      German MS centers (n=73) among NAT-treated MS patients (n=801) and their
      neurologists (n=99). Patients included in this study had mean disease duration of
      10.2years and a mean NAT treatment duration of 24months. RESULTS: More than 90%
      of patients and physicians voted for shared decision making or an informed choice
      decision making approach. Patients and physicians perceived a similar threat from
      MS as serious disease and both overestimated treatment benefits from NAT based on
      trial data. Men perceived MS more severe than women and perception of seriousness
      increased with age in both groups and in patients as well with increasing
      disability. Although patients evaluated their PML risk higher, their risk
      acceptance was significantly higher than of their neurologists. Risk
      stratification knowledge was good among neurologists and significantly lower
      among patients. CONCLUSION: While patients and physicians seem to have realistic
      risk perception of PML and knowledge of risk stratification concepts, the threat
      of MS and the perception of treatment benefits may explain the ongoing high
      acceptance of PML risk.

PMID- 28431610
TI  - Duration of paroxysmal atrial fibrillation in cryptogenic stroke is not
      associated with stroke severity and early outcomes.
AB  - The current definition of paroxysmal atrial fibrillation (PAF) requires an
      arbitrary cut-off of >30s, but in clinical practice cryptogenic stroke (CS)
      patients with PAF duration of <=30s are not usually excluded from anticoagulation
      therapy. We sought to evaluate the clinical relevance of short-duration (<=30s)
      PAF in CS. Consecutive CS patients with no prior AF history and sinus-rhythm on
      baseline electrocardiography (ECG) were prospectively evaluated over a three-year
      period. Baseline stroke severity was assessed by NIHSS-scores. All patients
      underwent 24-hour Holter-ECG during hospitalization. ECG recordings were analyzed
      by two blinded investigators using dedicated analysis software. Total time in AF
      was calculated as the sum of each individual AF episode for patients with
      multiple episodes during monitoring. Patients were dichotomized in two groups
      using PAF total duration (<=30s & >30s). Early recurrent stroke and favorable
      functional outcome (FFO, defined as mRS-grades of 0-1) were evaluated during a
      three-month follow-up period. A total of 184 patients (66% men, mean age 57+/
      11years) with CS (median NIHSS-score 4, IQR: 2-7) were evaluated. PAF of any
      duration was detected in 23 individuals (13%; 95%CI: 8%-18%). Among these
      patients the prevalence of brief PAF was 57% (n=13). The two groups did not
      differ (p>0.2) in terms of demographics, vascular risk factors and NIHSS-scores.
      Early recurrent stroke and FFO rates were similar (p>0.4) in the two groups.
      Duration of PAF is not associated with baseline stroke severity and early
      outcomes in patients with CS and should not influence anticoagulation decision in
      these patients.

PMID- 28431611
TI  - Transient global amnesia: The cerebral Takotsubo?

PMID- 28431612
TI  - Xeroderma pigmentosum complementation group F: A rare cause of cerebellar ataxia
      with chorea.
AB  - The complementation group F of Xeroderma pigmentosum (XP-F) is rare in the
      Caucasian population, and usually devoid of neurological symptoms. We report two
      cases, both Caucasian, who exhibited progressive cerebellar ataxia, chorea, a
      mild subcortical frontal cognitive impairment, and in one case severe
      polyneuropathy. Brain MRI demonstrated cerebellar (2/2) and cortical (1/2)
      atrophy. Both patients had only mild sunburn sensitivity and no skin cancer. Mini
      exome sequencing approach revealed in ERCC4, two heterozygous mutations, one of
      which was never described (c.580-584+1delCCAAGG, exon 3), in the first case, and
      an already reported homozygous mutation, in the second case. These cases
      emphasize that XP-F is a rare cause of recessive cerebellar ataxia and can in
      some cases clinically mimic Huntington's disease due to chorea and executive
      impairment. The association of ataxia, chorea, and sun hypersensitivity are major
      guidance for the diagnosis, which should not be missed, in order to prevent skin
      neoplastic complications.

PMID- 28431613
TI  - An analysis of prognostic factors after percutaneous endoscopic gastrostomy
      placement in Japanese patients with amyotrophic lateral sclerosis.
AB  - A percutaneous endoscopic gastrostomy (PEG) is an useful intervention for feeding
      of amyotrophic lateral sclerosis (ALS) patients who have lost oral intake
      function. The aim of this study was to investigate the risk factors for early
      death and the survival after PEG placement. A total of 102 ALS patients who
      underwent PEG placement were enrolled in this study. Patients were divided into
      two groups; the poor prognosis group included patients who died or needed
      permanent mechanical ventilation within 30days after PEG placement, and the good
      prognosis group included patients who did not meet the criteria of the poor
      prognosis group. Clinical characteristics, respiratory function, and nutritional
      parameters were compared for the two groups to assess the correlations between
      clinical and laboratory variables and early death after PEG placement.
      Multivariate analysis between two groups revealed that higher arterial carbon
      dioxide pressure (PaCO2) and aphagia before PEG placement were significantly
      associated with the poor prognosis group. Multivariate analysis for survival also
      revealed that higher PaCO2 and shorter duration from onset to PEG placement were
      significantly associated with shorter survival after PEG placement. In
      conclusion, respiratory and nutritional parameters are revealed to be important
      prognostic factors for ALS patients who undergo PEG placement.

PMID- 28431614
TI  - Permeability surface area product analysis in malignant brain edema prediction -
      A pilot study.
AB  - BACKGROUND AND PURPOSE: Using an extended CT perfusion acquisition (150s), we
      sought to determine the association between perfusion parameters and malignant
      edema after ischemic stroke. METHODS: Patients (from prospective study PROVE-IT,
      NCT02184936) with terminal internal carotid artery+/-proximal middle cerebral
      occlusion were involved. CTA was assessed for clot location and status of
      leptomeningeal collaterals. The following CTP parameters were calculated within
      the ischemic territory and contralaterally: permeability surface area product
      (PS), cerebral blood flow (CBF) and cerebral blood volume (CBV). PS was
      calculated using the adiabatic approximation to the Johnson and Wilson model.
      Outcome was evaluated by midline shift and infarction volume on follow-up
      imaging. RESULTS: Of 200 patients enrolled, 7 patients (3.5%) had midline
      shift>=5mm (2 excluded for poor-quality scans). Five patients with midline shift
      and 5 matched controls were analysed. There was no significant difference in mean
      PS, CBF and CBV within the ischemic territory between the two groups. A CBV
      threshold of 1.7ml/100g had the highest AUC=0.72, 95% CI=0.54-0.90 for early
      midline shift prediction, sensitivity and specificity were 0.83 and 0.67
      respectively. CONCLUSION: Our preliminary results did not show significant
      differences in permeability surface area analysis if analysed for complete
      ischemic region. CBV parameter had the highest accuracy and there was a trend for
      the mean PS values for midline shift prediction.

PMID- 28431616
TI  - Head drop in Parkinson's disease complicated by myasthenia gravis and myopathy.

PMID- 28431615
TI  - Association between PTGS1 polymorphisms and functional outcomes in Chinese
      patients with stroke during aspirin therapy: Interaction with smoking.
AB  - PURPOSE: Prostaglandin-Endoperoxide Synthase 1 (PTGS1) and smoking may play
      important roles in aspirin nonresponsiveness, but the effect of their interaction
      on stroke outcomes remains largely unknown. We examined the effects of PTGS1
      polymorphisms, smoking status, and their interaction on functional outcomes in a
      cohort of Chinese Han patients with stroke during aspirin therapy. METHODS: A
      total of 617 ischemic stroke patients taking aspirin were enrolled. Three single
      nucleotide polymorphisms (SNPs) rs1330344, rs3842788, and rs5788 in PTGS1 were
      determined for genotyping. Poor functional outcomes were defined as a modified
      Rankin Scale (mRS) of 3-6 at 90-day follow-up. The influence of PTGS1 gene
      smoking interaction on functional outcomes was examined. RESULTS: Poor functional
      outcomes occurred in 145 (23.5%) patients. When adjusting multiple factors by
      logistic regression, CC genotype of rs1330344 was associated with poor functional
      outcomes (risk ratio [RR]=1.73; 95% confidence interval [CI]: 1.17-2.37). A
      similar connection was found in the CGC haplotype (RR=1.40; 95% CI: 1.08-1.77).
      Furthermore, we found a significant interaction between rs1330344 and smoking
      status (Pinteraction=0.018); the interaction effect between the PTGS1 haplotype
      and smoking also showed statistical significance (Pinteraction=0.040).
      CONCLUSIONS: In Chinese Han stroke patients with aspirin therapy, the adverse
      effect of PTGS1 polymorphisms on functional outcomes may be modulated by the
      smoking status. PTGS1 gene-smoking interaction might in part reflect the
      heterogeneity in the prognosis of patients treated with aspirin.

PMID- 28431617
TI  - Short-term outcome of functional integrity of the auditory brainstem in term
      infants who suffer perinatal asphyxia.
AB  - OBJECTIVES: To assess short-term outcome of impaired functional integrity of the
      auditory brainstem in term infants who suffer perinatal asphyxia. METHODS:
      Maximum length sequence brainstem auditory evoked response (MLS BAER) was
      recorded and analyzed at a mean age of 3months in term infants after perinatal
      asphyxia. The data were compared with age-matched normal term infants. RESULTS:
      The infants after asphyxia showed an increase in the latency of MLS BAER wave III
      at 91, 455 and 910/s, and wave V at all click rates of 91-910/s. The interpeak
      intervals in the infants after asphyxia were increased at almost all click rates.
      The IV and I-III intervals were increased at all click rates, and the III-V
      interval was increased at 455 and 910/s. These increases were generally more
      significant at higher than at lower click rates. The amplitudes of waves I, III
      and V in the infants after asphyxia were reduced at all click rates. The V/I
      amplitude ratio was increased at 91-455/s clicks. The slope of III-V interval
      rate function was abnormally increased. 17.1% of the infants after asphyxia had
      an abnormal increase in IV intervals. CONCLUSIONS: MLS BAER was moderately
      abnormal at 3months of age in term infants after perinatal asphyxia, suggesting
      moderate impairment in the functional integrity of the auditory brainstem. The
      impairment occurs in 17.1% of the infants. Compared with that found at term, the
      impairment has improved, but not completely recovered.

PMID- 28431618
TI  - Muscle strength and power in persons with multiple sclerosis - A systematic
      review and meta-analysis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic disease in the central nervous
      system which causes a number of physical symptoms including impairments of muscle
      mechanical function (muscle strength, muscle power and explosive muscle strength
      (~rate of force development, RFD)). However, a full overview of the existing
      knowledge regarding muscle mechanical function in persons with MS (PwMS) is still
      pending. OBJECTIVES: To systematically review 1) the psychometric properties of
      isokinetic dynamometry testing in PwMS, and 2) studies comparing muscle
      mechanical function in PwMS to matched healthy controls (HC). In addition, a meta
      analysis will evaluate 3) the effects of progressive resistance training on
      muscle mechanical function in PwMS. METHODS: A systematic literature search was
      performed in eight databases. To be included in the review, the study had to 1)
      enroll participants with a confirmed diagnosis of MS; 2) assess muscle mechanical
      function 3) had undergone peer-review. The psychometric properties of isokinetic
      dynamometry were reviewed with respect to validity, reliability, and
      responsiveness. Comparison of muscle strength between PwMS and HC was performed
      across contraction velocities, contraction modes and muscle groups, as were the
      rate of force development. The effects of progressive resistance training on
      muscle mechanical function were evaluated in a meta-analysis using a random
      effects model and standardized mean difference (SMD). RESULTS: A total of four,
      twenty-four, and ten studies were identified for aim 1, 2, and 3, respectively.
      High Intraclass correlations coefficients (range: 0.87-0.99) for isokinetic
      dynamometry was reported when assessing knee extensor and knee flexor muscle
      strength independent of contraction velocity. Compared to match HC, PwMS display
      impaired muscle strength, power and explosive muscle strength. Muscle strength
      impairments were most pronounced during maximal moderate to fast dynamic muscle
      contractions of the lower extremities. Progressive resistance training has a
      small but significant effect on muscle mechanical function in PwMS (SMD=0.45, 95%
      CI: 0.18-0.72, p=0.001). CONCLUSIONS: The present review showed that 1)
      isokinetic dynamometry has a high reliability in PwMS; 2) muscle strength, power
      and rate of force development is impaired in PwMS compared to HC, and muscle
      strength impairments are most pronounced during maximal moderate to fast dynamic
      muscle contractions of the lower extremities; and 3) progressive resistance
      training can improve muscle mechanical function in PwMS. Future studies should
      evaluate progressive resistance training designed to optimize maximal moderate to
      fast dynamic muscle contractions of the lower extremities.

PMID- 28431619
TI  - Age, sex, and race/ethnic temporal trends in metabolic syndrome prevalence among
      individuals with myocardial infarction or stroke in the United States.
AB  - INTRODUCTION: Metabolic syndrome (MetS), an independent risk factor for
      myocardial infarction (MI) and stroke, affects 1 in 3 adults in the United
      States. Recent trends in MetS prevalence among MI and stroke survivors are
      unknown. METHODS: We assessed age, sex, race/ethnicity, and socio-economic status
      specific trends in rates of MetS among adults >=18years who participated in
      National Health and Nutrition Examination Surveys 1999-2010 and who fasted for 8h
      (n=12,502). MetS was defined using the 2009 harmonized definition. MI and stroke
      were defined by self-reported diagnosis by a health care provider. RESULTS: MetS
      prevalence was 65.8% (2.2%) in MI survivors (n=663) and 61.2% (3.8%) in stroke
      survivors (299). Women aged 35 to 64years with prior MI were more likely to have
      MetS compared to similarly aged stroke survivors (unadjusted OR 3.13, 95% CI 1.38
      7.10). MetS prevalence among MI/stroke survivors remained flat from 1999 to 2010
      in all groups except non-Hispanic blacks with prior MI, in whom prevalence
      increased. From 1999 to 2010, dyslipidemia declined and abdominal obesity and
      hyperglycemia increased among individuals with prior MI. MetS components remained
      unchanged among those with prior stroke. CONCLUSION: The persistent high
      prevalence of MetS among stroke and MI survivors highlights the need for more
      effective interventions.

PMID- 28431620
TI  - Role of inflammatory molecules in the Alzheimer's disease progression and
      diagnosis.
AB  - Alzheimer's disease (AD) is a complex disorder and the most common form of
      neurodegenerative dementia. Several genetic, environmental, and physiological
      factors, including inflammations and metabolic influences, are involved in the
      progression of AD. Inflammations are composed of complicated networks of many
      chemokines and cytokines with diverse cells. Inflammatory molecules are needed
      for the protection against pathogens, and maintaining their balances is important
      for normal physiological function. Recent studies demonstrated that inflammation
      may be involved in neurodegenerative dementia. Cellular immune components, such
      as microglia or astrocytes, mediate the release of inflammatory molecules,
      including tumor necrosis factor, growth factors, adhesion molecules, or
      chemokines. Over- and underexpression of pro- and anti-inflammatory molecules,
      respectively, may result in neuroinflammation and thus disease initiation and
      progression. In addition, levels of several inflammatory factors were reported to
      be altered in the brain or bodily fluids of patients with AD, reflecting their
      neuropathological changes. Therefore, simultaneous detection of several
      inflammatory molecules in the early or pre-symptomatic stage may improve the
      early diagnosis of AD. Further studies are needed to determine, how induction or
      inhibition of inflammatory factors could be used for AD therapies. This review
      summarizes the role or possible role of immune cells and inflammatory molecules
      in disease progression or prevention.

PMID- 28431621
TI  - Two decades of glatiramer acetate: From initial discovery to the current
      development of generics.
AB  - Multiple sclerosis (MS) is a chronic, incurable, inflammatory disease of the
      central nervous system (CNS). In the United States, several US Food and Drug
      Administration (FDA)-approved disease-modifying treatments (DMTs) are available,
      including glatiramer acetate (GA; Copaxone(r)), one of the most longstanding
      treatments. GA was discovered serendipitously in the late 1960s/early 1970s while
      attempting to produce a synthetic antigen capable of inducing experimental
      autoimmune encephalomyelitis (EAE), an animal model of autoimmune inflammatory
      CNS disorders, including MS. Instead, GA was found to be protective in EAE
      models. Subsequent clinical evaluations resulted in GA's FDA approval for
      relapsing-remitting MS in 1996, followed by a change to the current indication of
      relapsing forms of MS along with approval of a higher dose and less frequently
      administered version in 2014. The cost of DMTs including GA remains high,
      highlighting the potential value of generic therapies for MS. A rigorous
      scientific approach may be undertaken to demonstrate equivalence between the
      generic and innovator drug. The introduction of generic versions of GA into the
      MS treatment landscape has the potential to reduce treatment costs, improving
      access to these much-needed treatments.

PMID- 28431622
TI  - Quantitative biomechanical assessment of trunk control in Huntington's disease
      reveals more impairment in static than dynamic tasks.
AB  - Postural instability is common in individuals with Huntington's disease (HD), yet
      little is known about control of the trunk during static and dynamic activities.
      We compared the trunk motion of 41 individuals with HD and 36 controls at
      thoracic and pelvic levels during sitting, standing, and walking using wearable
      iPod sensors. We also examined the ability of individuals with HD to respond to
      an auditory cue to modify trunk position when the pelvis moved >8 degrees  in
      sagittal or frontal planes during sitting using custom software. We found that
      amplitude of thoracic and pelvic trunk movements was significantly greater in
      participants with HD, and differences were more pronounced during static (i.e.
      sitting, standing) than dynamic (i.e. walking) tasks. In contrast to the slow,
      smooth sinusoidal trunk movements of controls, individuals with HD demonstrated
      rapid movements with varying amplitudes that continuously increased without
      stabilizing. Ninety-seven percent of participants with HD were able to modify
      their trunk position in response to auditory cues. Our results demonstrate that
      wearable iPod sensors are clinically useful for rehabilitation professionals to
      measure and monitor trunk stability in persons with HD. Additionally, auditory
      cueing holds potential as a useful training tool to improve trunk stability in
      HD.

PMID- 28431623
TI  - A unique case of dysferlinopathy with a large-segment duplication mutation who
      experienced rapid deterioration after small-dosage corticosteroid treatment.

PMID- 28431624
TI  - Opsoclonus myoclonus ataxia associated with West Nile virus infection: A dramatic
      presentation with benign prognosis?
AB  - Opsoclonus myoclonus and ataxia is a combination of severe neurological signs
      associated with several pathologic agents and conditions. Only few cases of
      opsoclonus have been related to West Nile virus infection. We report on a 61-year
      old woman and on a 55-year-old man who had history of recent fever, who were
      hospitalized because of acute severe truncal ataxia, opsoclonus and tremor with
      minimal myoclonic jerks. A through work-up revealed the presence of both IgM and
      IgG antibodies against West Nile virus both in the serum and Cerebrospinal Fluid
      and excluded other causes known to be associated with this combination of
      neurological signs. The first case was treated with corticosteroids, followed by
      significant improvement, and the second recovered spontaneously. The acute
      combination of opsoclonus, severe truncal ataxia and tremor with a history of
      recent fever requires, during the relevant season and in the relevant geographic
      area, a search for a recent infection with West Nile virus. Though initially
      suffering from a devastating sickness, our patients eventually recovered.

PMID- 28431625
TI  - TPK1 mutation induced childhood onset idiopathic generalized dystonia: Report of
      a rare mutation and effect of deep brain stimulation.

PMID- 28431626
TI  - Sleep patterns in villagers and urban African volunteers in a humid tropical
      climate: Influence of accessibility to electric light?
AB  - Recent publications focusing on sleep-wake alternation, using actigraphic
      recordings in hunter-gatherers, stressed the existence of a potential effect of
      electricity availability on sleep habits. These reports prompted us to achieve a
      new analysis of the polysomnographic data already obtained in healthy African
      volunteers in equatorial Africa during two different investigations. Comparison
      of the 24-h polysomnographic sleep patterns were done between 9 volunteers
      sleeping in a laboratory in Abidjan (Abidjan cohort) and 11 villagers living in
      electricity-free bush villages (Sinfra cohort). Sleep was lighter in the
      villagers, with more stage 1 and less slow wave sleep (SWS). Latency to SWS was
      also shorter. Total sleep time, however, was not different between the two
      groups. There were no indications as to whether the observed differences were
      attributable to the availability of electrical power. Reactivity of human sleep
      structure to the environment was discussed in terms of multifactorial influences
      such as daylight length, temperature, humidity, electromagnetic field, time of
      sleep onset, thermoregulatory mechanisms, stress or anxiety.

PMID- 28431627
TI  - Sequential NAION presenting as pseudo Foster Kennedy syndrome.
AB  - PURPOSE: To review recurrent NAION as a cause for PFK syndrome. METHODS: In an
      observational study patients presenting with sudden loss of vision were
      evaluated. We reviewed patients presenting with disc edema on one side and optic
      atrophy in contralateral eye on fundus examination. Their visual field defects
      and fundus fluorescein angiography was assessed. RESULTS: Of the 7 patients
      evaluated 4 (57.1%) were females. Mean age at presentation was 53.7+/-11.9years.
      Mean duration between the two episodes was 12.7months (range: 2-30). The visual
      acuity of presenting eye ranged from 6/9 to worse counting fingers close to face.
      CONCLUSIONS: The diagnosis in a PFK presentation is essentially one of exclusion.
      Patients with NAION are at risk for recurrence in fellow eye, thereby presenting
      as PFK syndrome. NAION should be considered as a differential especially when
      imaging and other laboratory investigations are not suggestive of any compressive
      lesion.

PMID- 28431628
TI  - Clinical and quantitative analysis of patients with crowned dens syndrome.
AB  - BACKGROUND: Crowned dens syndrome (CDS) is a radioclinical entity defined by
      calcium deposition on the transverse ligament of atlas (TLA). In this study, the
      novel semi-quantitative diagnostic criteria for CDS to evaluate the degree of
      calcification on TLA by cervical CT are proposed. METHOD: From January 2010 to
      September 2014, 35 patients who were diagnosed with CDS by cervical CT were
      adopted as subjects in this study. Based on novel criteria, calcium deposition on
      TLA was classified into "Stage" and "Grade", to make a score, which was evaluated
      semi-quantitatively. The correlation between calcification score and CRP level or
      pain score, and the effects of treatments, such as NSAIDs and corticosteroids,
      were statistically analyzed. RESULTS: The total calcification score from added
      "Stage" and "Grade" scores demonstrated a significantly strong and linear
      correlation with CRP level (R2=0.823, **p<0.01). In the multiple comparison test
      for the treatment effects, significant improvement of the CRP level and pain
      score were demonstrated after corticosteroid therapy (**p<0.01) compared with
      NSAIDs. In the conditional logistic regression analysis, the rapid end of
      corticosteroid therapy was an independent risk factor for relapse of cervico
      occipital pain [OR=50.761, *p=0.0419]. CONCLUSION: The degree of calcification on
      TLA evaluated by the novel semi-quantitative criteria significantly correlated
      with CRP level. In the treatment of CDS, it is recommended that a low dosage (15
      30mg) of corticosteroids be used as first-line drugs rather than conventional
      NSAID therapy. Additionally, it is also recommended to gradually decrease the
      dosage of corticosteroids.

PMID- 28431629
TI  - Spinocerebellar ataxia type 6 presenting with parkinsonism, pre-synaptic
      dopaminergic dysfunction and hyperechogenicity of the substantia nigra.

PMID- 28431630
TI  - Kynurenic acid and its analogue can alter the opioid receptor G-protein signaling
      after acute treatment via NMDA receptor in rat cortex and striatum.
AB  - Previously, we have shown that the N-methyl d-aspartate (NMDA)-receptor
      antagonist kynurenic acid (KYNA) and its analogue KYNA1 do not bind directly to
      mu, kappa and delta opioid receptors in vitro. On the other hand, chronic
      administration of KYNA and KYNA1 resulted in region (cortex vs striatum) and
      opioid receptor-type specific alterations in G-protein activation of mouse brain
      homogenates. Here we describe for the first time the acute effect of KYNA and
      KYNA1 on opioid receptor function with the possible involvement of the NMDA
      receptor. The acute 30minute in vivo KYNA1 and KYNA treatments altered opioid
      receptor G-protein signaling or ligand potency depending on the opioid receptor
      type and brain region (rat cortex vs striatum) using [35S]GTPgammaS binding
      assays. Pretreatment with the NMDA receptor antagonist MK-801 impaired or
      reversed the effects of KYNA1 and KYNA. These results suggest an NMDA receptor
      mediated effect. After acute 30minute treatment HPLC measurements revealed a
      similar KYNA1 and a higher KYNA plasma concentration compared to cerebrospinal
      fluid concentrations. Finally, KYNA, KYNA1 and MK-801 showed comparable results
      in opioid receptor G-protein activity and ligand potency with acute in vivo
      treatments when they were administered in vitro for 30min on isolated cortex and
      striatum slices. We previously demonstrated that KYNA1 and KYNA acutely altered
      opioid receptor function in vivo and in vitro through the NMDA receptor depending
      on the opioid receptor type and brain region. This study may lead to a new,
      indirect approach to influence opioid receptor signaling.

PMID- 28431631
TI  - Neuroimaging findings in Joubert syndrome with C5orf42 gene mutations: A milder
      form of molar tooth sign and vermian hypoplasia.
AB  - PURPOSE: Little is known regarding neuroimaging-genotype correlations in Joubert
      syndrome (JBTS). To elucidate one of these correlations, we investigated the
      neuroimaging findings of JBTS patients with C5orf42 mutations. MATERIALS AND
      METHODS: Neuroimaging findings in five JBTS patients with C5orf42 mutations were
      retrospectively assessed with regard to the infratentorial and supratentorial
      structures on T1-magnetization prepared rapid gradient echo (MPRAGE), T2-weighted
      images, and color-coded fractional anisotropy (FA) maps; the findings were
      compared to those in four JBTS patients with mutations in other genes (including
      three with AHI1 and one with TMEM67 mutations). RESULTS: In C5orf42-mutant
      patients, the infratentorial magnetic resonance (MR) images showed normal or
      minimally thickened and minimally elongated superior cerebellar peduncles (SCP),
      normal or minimally deepened interpeduncular fossa (IF), and mild vermian
      hypoplasia (VH). However, in other patients, all had severe abnormalities in the
      SCP and IF, and moderate to marked VH. Supratentorial abnormalities were found in
      one individual in other JBTS. In JBTS with all mutations, color-coded FA maps
      showed the absence of decussation of the SCP (DSCP). CONCLUSION: The
      morphological neuroimaging findings in C5orf42-mutant JBTS were distinctly mild
      and made diagnosis difficult. However, the absence of DSCP on color-coded FA maps
      may facilitate the diagnosis of JBTS.

PMID- 28431632
TI  - Combined evaluation of personality, risk and coping in MS patients: A step
      towards individualized treatment choice - The PeRiCoMS-Study I.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory neurological
      disease requiring disease-modifying treatment (DMT). To provide patients with the
      optimal individual therapeutic option, treatment recommendations should be based
      not only on individual disease course and DMT specific benefit-risk estimates,
      but also on patient's individual characteristics such as personality, risk
      attitude and coping strategies. However, these characteristics are difficult to
      objectify in clinical routine practice without the support of appropriate
      evaluation instruments. OBJECTIVE: To identify and to assemble an objective test
      battery measuring personality, risk attitude and coping strategies in MS
      patients. METHODS: A comprehensive literature search was performed to obtain all
      questionnaires assessing personality, risk attitude and coping strategies.
      Availability in German language, validation in a published normative collective
      and a reliability of >0.70 were required for our purposes. Based on these
      criteria, we chose the Big-Five-Personality Test, UPPS Impulsive Behaviour Scale,
      Domain-Specific Risk-Taking scale (DOSPERT), Brief-COPE and Stress & Coping
      Inventory (SCI). Results were compared to published normative controls of the
      respective questionnaires. RESULTS: Out of 22 MS patients (7 males, 15 females)
      participating in this study, 19 (86.4%) completed all questionnaires. The median
      completion time was 45min (min-max range: 25-60min). The median scores of the MS
      group were within the average range of published control samples in all
      questionnaires. CONCLUSIONS: We report that traits of personality, risk attitude
      and coping strategies can be effectively and feasibly tested in MS patients by
      the instruments used in our exploratory study. There were no differences between
      MS patients and healthy controls, thus enabling assessment without being
      influenced by the diagnosis of MS. After validation in a larger cohort the
      "PeRiCoMS"-battery will be useful as another step towards a more individualized
      shared-decision-making in every day routine practice.

PMID- 28431633
TI  - Greater healthcare utilization and costs among Black persons compared to White
      persons with aphasia in the North Carolina stroke belt.
AB  - PURPOSE: To examine racial differences in healthcare utilization and costs for
      persons with aphasia (PWA) being treated in acute care hospitals in North
      Carolina (NC). METHODS: NC Healthcare Cost and Utilization Project State
      Inpatient Database (HCUP-SID) data from 2011-2012 were analyzed to examine
      healthcare utilization and costs of care for stroke patients with aphasia.
      Analyses emphasized length of stay, charges and cost of general hospital
      services. Generalized linear models (GLM) were constructed to determine the
      impact of demographic characteristics, stroke/illness severity, and observed
      hospital characteristics on utilization and costs. Hospital fixed effects were
      included to yield within-hospital estimates of disparities. RESULTS: GLM models
      demonstrated that Blacks with aphasia experienced 1.9days longer lengths of stay
      compared to Whites with aphasia after controlling for demographic
      characteristics, 1.4days controlling for stroke/illness severity, 1.2days
      controlling for observed hospital characteristics, and ~1 extra day controlling
      for unobserved hospital characteristics. Similarly, Blacks accrued ~$2047 greater
      total costs compared to Whites after controlling for demographic characteristics,
      $1659 controlling for stroke/illness severity, $1338 controlling for observed
      hospital characteristics, and ~$1311 greater total costs after controlling for
      unobserved hospital characteristics. CONCLUSIONS: In the acute hospital setting,
      Blacks with aphasia utilize greater hospital services during longer
      hospitalizations and at substantially higher costs in the state of NC. A
      substantial portion of the adjusted difference was related to the hospital
      treating the patient. However, even after controlling for the hospital, the
      differences remained clinically and statistically significant.

PMID- 28431634
TI  - Multicenter observational study of abobotulinumtoxinA neurotoxin in cervical
      dystonia: The ANCHOR-CD registry.
AB  - BACKGROUND: The ANCHOR-CD prospective observational registry study evaluated the
      effectiveness of abobotulinumtoxinA in adult idiopathic cervical dystonia (CD) in
      clinical practice. METHODS: Adults with CD were eligible. Treating physicians
      determined abobotulinumtoxinA dose and treatment interval. The primary endpoint
      was patient response rate (Toronto Western Spasmodic Torticollis Rating Scale
      [TWSTRS] score reduction>=25% and Patient Global Impression of Change [PGIC]
      score of +2 or +3 at Week 4 of Cycle 1). RESULTS: 350 patients enrolled (75%
      women; mean age 59+/-13.6years; 27.4% botulinum neurotoxin-naive) and 347
      received at least 1 treatment. The median abobotulinumtoxinA dose for Cycle 1 was
      500 Units. At Week 4, the responder rate was 30.6% (n=304) and the TWSTRS total
      score decreased 27.4% from baseline. PGIC of at least "Much improved" was
      documented in 43.6% of patients and maintained in Cycles 2 through 4 (43.3%,
      48.9%, and 52.8%, respectively). A total of 39 adverse events (31 study drug
      related) were reported in 17 patients (5%); the most common were dysphagia (n=6),
      muscle weakness (n=4), and neck pain (n=3). CONCLUSION: This study confirmed the
      beneficial effect of abobotulinumtoxinA on CD in routine clinical practice as
      measured by improvements in TWSTRS and PGIC. No new safety concerns were
      identified.

PMID- 28431635
TI  - A case of superior sagittal sinus intracranial dural arteriovenous fistula
      mimicking corticobasal syndrome.

PMID- 28431636
TI  - Systemic air embolism after endoscopy without vessel injury - A summary of
      reported cases.
AB  - INTRODUCTION: Systemic air embolism (SAE) is a rare but serious complication
      following endoscopic procedures. It may occur with or without direct vessel
      injury. The aim of this work is to review cases of SAE following endoscopy
      without proven vessel injury. METHODS: In this systematic review PubMed database
      was screened for SAE following endoscopy from 1990 to 2015. Only cases without
      proven major vessel injury were included in the analysis. Including one case of
      SAE after colonoscopy from our hospital the analysis comprised 40 cases. RESULTS:
      60% of patients underwent ERCP, 33% gastroscopy and the remaining 7% other
      endoscopic procedures. Among patients suffering from SAE the majority had
      cerebral embolism (73%). In 46% of documented echocardiography a patent foramen
      ovale (PFO) has been confirmed as mechanism of paradoxical air embolism.
      Therapeutic approaches comprised most frequently hyperbaric oxygenation. In 35%
      of cases advanced life support was necessary whereas only 55% of patients
      survived SAE in total. CONCLUSION: SAE is a serious complication of endoscopic
      procedures with high morbidity and mortality. In patients with present PFO high
      awareness should be paid to informed consent for the risk of SAE, especially
      stroke. Cautiousness with sedation is necessary in those patients not to delay
      clinical recognition of neurological SAE symptoms.

PMID- 28431637
TI  - Transcranial color-coded sonography of vertebral artery for diagnosis of right-to
      left shunts.
AB  - BACKGROUND: It is unknown whether contrast transcranial color-coded sonography of
      vertebral artery monitoring via the foramen magnum window (cTCCS-VA) is useful to
      detect right-to-left shunt (RLS). We investigated whether cTCCS-VA can be
      proposed as an alternative to middle cerebral artery monitoring via the temporal
      bone window (cTCCS-MCA) for RLS detection, as compared with contrast
      transesophageal echocardiography (cTEE). METHODS: We evaluated 112 patients with
      ischemic stroke or transient ischemic attack. We compared the sufficiency of both
      acoustic windows in each age tertile. Then, we analyzed the accuracy of cTCCS in
      diagnosing an RLS for a patent foramen ovale (PFO) detected by cTEE. RESULTS: In
      the higher-age tertile, the foramen magnum window was significantly more
      sufficient than the temporal bone window (100% vs. 71%, p<0.001). In 94 patients
      having both windows, diagnosis of an RLS using cTCCS-MCA revealed a specificity
      of 42%, and a sensitivity of 84%. Diagnosis of an RLS using cTCCS-VA revealed a
      specificity of 40%, and a sensitivity of 91%. Analysis of the subgroup with large
      PFOs revealed a specificity of 71% using both cTCCS-MCA and cTCCS-VA.
      CONCLUSIONS: cTCCS-VA should play an important role in detecting an RLS,
      especially in elderly stroke patients having large PFOs.

PMID- 28431638
TI  - Triglycerides Revisited to the Serial.
AB  - This review discusses the role of triglycerides (TGs) in the normal
      cardiovascular system as well as in the development and clinical manifestation of
      cardiovascular diseases. Regulation of TGs at the enzymatic and genetic level, in
      addition to their possible relevance as preclinical and clinical biomarkers, is
      discussed, culminating with a description of available and emerging treatments.
      Due to the high complexity of the subject and the vast amount of material in the
      literature, the objective of this review was not to exhaust the subject, but
      rather to compile the information to facilitate and improve the understanding of
      those interested in this topic. The main publications on the topic were sought
      out, especially those from the last 5 years. The data in the literature still
      give reason to believe that there is room for doubt regarding the use of TG as
      disease biomarkers; however, there is increasing evidence for the role of
      hypertriglyceridemia on the atherosclerotic inflammatory process, cardiovascular
      outcomes, and mortality.

PMID- 28431639
TI  - Advances in Molecular Diagnosis of Malaria.
AB  - Malaria is a mosquito-borne disease caused by five species of Plasmodium
      parasites. Accurate diagnosis of malaria plays an essential part in malaria
      control. With traditional diagnostic methodologies, malaria control programs have
      achieved remarkable success during the past decade, and are now heading toward
      malaria elimination in many areas. This new situation, however, calls for novel
      diagnostics with improved sensitivity, throughput, and reduced cost for active
      screening of malaria parasites, as all transfected individuals have to be
      identified in order to block transmission. In this chapter, we provide a brief
      introduction of malaria, the requirement of diagnostic advances in the age of
      malaria elimination, and a comprehensive overview of the currently available
      molecular malaria diagnostics, ranging from well-known tests to platforms in
      early stages of evaluation. We also discussed several practical issues for the
      application of molecular tests in malaria identification.

PMID- 28431640
TI  - Rapid Assessment of Drugs of Abuse.
AB  - Laboratory testing for drugs of abuse has become standard practice in many
      settings both forensic and clinical. Urine is the predominant specimen, but other
      specimens are possible including hair, nails, sweat, and oral fluid. Point-of
      care test kits provide for rapid analysis at the site where specimens are
      collected allowing for immediate action on the results. POCT is based on
      immunochromatography where the drug in the patient's sample competes with drug
      and antibody conjugates in the test to develop or block the development of a
      colored line. Most POCTs are visually interpreted in a few minutes. The potential
      for false positives is possible due to drug cross-reactivity with the antibodies
      in the test. False negatives are also possible due to dilution of the sample and
      the potential for adulteration or sample substitution by the patient. POCT shows
      more variability than central laboratory testing because of the variety of
      operators involved in the testing process, but POCT has good agreement for most
      tests with mass spectrometry provided comparable cutoffs and cross-reactivity of
      drugs/metabolites are considered. Validation of the test performance with the
      intended operators will identify potential interferences and operational issues
      before implementing the test in routine practice. POCT offers faster turnaround
      of test results provided the limitations and challenges of the test are
      considered.

PMID- 28431641
TI  - Infections: A Possible Risk Factor for Type 2 Diabetes.
AB  - Diabetes mellitus is one of the biggest challenges to human health globally, with
      an estimated 95% of the global diabetic population having type 2 diabetes.
      Classical causes for type 2 diabetes, such as genetics and obesity, do not
      account for the high incidence of the disease. Recent data suggest that
      infections may precipitate insulin resistance via multiple mechanisms, such as
      the proinflammatory cytokine response, the acute-phase response, and the
      alteration of the nutrient status. Even pathogen products, such as
      lipopolysaccharide and peptidoglycans, can be diabetogenic. Therefore, we argue
      that infections that are known to contribute to insulin resistance should be
      considered as risk factors for type 2 diabetes.

PMID- 28431642
TI  - PCR-Based Detection Methods for Single-Nucleotide Polymorphism or Mutation: Real
      Time PCR and Its Substantial Contribution Toward Technological Refinement.
AB  - Single-nucleotide polymorphisms (SNPs) and single-nucleotide mutations result
      from the substitution of only a single base. The SNP or mutation can be relevant
      to disease susceptibility, pathogenesis of disease, and efficacy of specific
      drugs. It is important to detect SNPs or mutations clinically. Methods to
      distinguish/detect SNPs or mutations should be highly specific and sensitive. In
      this regard, polymerase chain reaction (PCR) has provided the necessary
      analytical performance for many molecular analyses. PCR-based methods for
      SNP/mutation detection are broadly categorized into two types-(1) polymorphic or
      mutant allele-directed specific analysis using primers matched with substituted
      nucleotide or using oligonucleotides to block or clamp the nontargeted template,
      and (2) melting curve analysis, which is combined with the real-time PCR
      techniques using hydrolysis probes, hybridization probes, or double-stranded DNA
      binding fluorescent dyes. Innovative and novel approaches as well as technical
      improvements have made SNP- or mutation-detection methods increasingly more
      sophisticated. These advances include DNA/RNA preparation and subsequent
      amplification steps, and miniaturization of PCR instruments such that testing may
      be performed with relative ease in clinical laboratories or as a point-of-care
      test in clinical settings.

PMID- 28431643
TI  - Advances in Circulating Tumor DNA Analysis.
AB  - The analysis of cell-free circulating tumor DNA (ctDNA) is a very promising tool
      and might revolutionize cancer care with respect to early detection,
      identification of minimal residual disease, assessment of treatment response, and
      monitoring tumor evolution. ctDNA analysis, often referred to as "liquid biopsy"
      offers what tissue biopsies cannot-a continuous monitoring of tumor-specific
      changes during the entire course of the disease. Owing to technological
      improvements, efforts for the establishment of preanalytical and analytical
      benchmark, and the inclusion of ctDNA analyses in clinical trial, an actual
      clinical implementation has come within easy reach. In this chapter, recent
      advances of the analysis of ctDNA are summarized starting from the discovery of
      cell-free DNA, to methodological approaches and the clinical applicability.

PMID- 28431645
TI  - Lopez PM, Islam N, Feinberg A, Myers C, Seidl L, Drackett E, Riley L, Mata A,
      Pinzon J, Benjamin E, Wyka K, Dannefer R, Lopez J, Trinh-Shevrin C, Maybank KA,
      Thorpe LE. A Place-Based Community Health Worker Program: Feasibility and Early
      Outcomes, New York City, 2015. Am J Prev Med 2017;52(3S3):S284-S289.

PMID- 28431644
TI  - Preface.

PMID- 28431646
TI  - A Question Mark on Thoracoabdominal Aneurysm.

PMID- 28431647
TI  - JVIR Editor's Awards: 2016 Top Papers.

PMID- 28431649
TI  - A Chylothorax of Gorham Disease Treated by Lymphatic Embolization.

PMID- 28431650
TI  - Rupture of Third Dorsal Metatarsal Artery after Balloon Angioplasty and Its
      Management.

PMID- 28431651
TI  - Modified Inside-Out Technique for Continued Use of Chronically Occluded Upper
      Central Veins.
AB  - This report describes a 2-step, inside-out procedure for upper body central
      venous access in patients with chronic central venous occlusions. Blunt cephalad
      dissection through the mediastinum was achieved with a curved metal cannula and
      guide wire followed by percutaneous puncture of an open snare from a right
      supraclavicular approach and dilation of the tract for a tunneled central venous
      catheter insertion. Of 9 patients, all had a successful placement of a tunneled
      central venous catheter using this method. Although this 2-step, inside-out
      technique is effective for creating access in the presence of central venous
      occlusion, further clinical evaluation is warranted.

PMID- 28431652
TI  - Primary Branch Vessel Embolization to Prevent Type 2 Endoleak before Stent Graft
      Treatment for Perforation of the Subclavian Artery.

PMID- 28431653
TI  - Extrahepatic Portal Vein Aneurysm at the Portal Bifurcation Treated with
      Transjugular Intrahepatic Portosystemic Shunt.

PMID- 28431654
TI  - Percutaneous Image-Guided Cryotherapy for Local Control of Recurrent Plexiform
      Schwannoma in a 3-Year-Old Male.

PMID- 28431655
TI  - Bubble Trouble: Air Embolism during Multiple EndoAnchor Application.

PMID- 28431656
TI  - Successful Treatment of Esophageal Stenosis in a Patient with Dystrophic
      Epidermolysis Bullosa Using Balloon Dilation.

PMID- 28431657
TI  - Meta-Analysis of Prostatic Artery Embolization for Benign Prostatic Hyperplasia
      Review of 12-Month Outcomes Data.

PMID- 28431658
TI  - Reply to: "Meta-Analysis of Prostatic Artery Embolization for Benign Prostatic
      Hyperplasia-Review of 12-Month Outcomes Data".

PMID- 28431659
TI  - Embolization of Type II Endoleaks.

PMID- 28431660
TI  - Reply to: "Embolization of Type II Endoleaks".

PMID- 28431661
TI  - Hwang JH, Do YS, Park KB, Chung HH, Park HS, Hyun D. Embolization of Congenital
      Renal Arteriovenous Malformations Using Ethanol and Coil Depending on
      Angiographic Types. (J Vasc Interv Radiol 2017; 28:64-70).

PMID- 28431662
TI  - Lekperic S, Livshits I, Tabori N, Patel R, Lookstein R, Kim E, Fischman A,
      Nowakowski F. Patient radiation exposure in hepatic chemoembolization utilizing
      cone-beam CT: comparison of transradial and transfemoral approaches. (J Vasc
      Interv Radiol 2017; 28:S128-S129).

PMID- 28431663
TI  - Effects of Torcetrapib and Statin Treatment on ApoC-III and Apoprotein-Defined
      Lipoprotein Subclasses (from the ILLUMINATE Trial).
AB  - In the ILLUMINATE Trial, treatment with the cholesteryl ester transfer protein
      inhibitor torcetrapib resulted in a significant increase in both atherosclerotic
      cardiovascular disease events and total mortality which was not explained by
      changes in the routinely measured plasma lipids. To determine whether alterations
      in lipoproteins defined by their apoprotein content that are not estimated with
      conventional laboratory methods contributed to these unexpected events, we
      measured the apoB- and apoA-containing subclasses in a subgroup of ILLUMINATE
      participants. We find that torcetrapib treatment significantly increased the high
      density lipoprotein subclasses LpA-I and LpA-I:A-II equally (p <0.0001) and the
      apoC-III content of high-density lipoprotein (p <0.001) without altering the apoB
      containing subclasses. In conclusion, these findings provide further evidence
      that the untoward effects of torcetrapib were attributable to off-target effects
      and not related to disturbances in lipoprotein transport.

PMID- 28431664
TI  - Considerations on Subgroup Analyses in Clinical Trials.

PMID- 28431665
TI  - GLP-1 receptor agonist confer target organ protection in type 2 diabetes.

PMID- 28431666
TI  - GLP-1 receptor agonists and heart failure in diabetes.
AB  - The prevalence of heart failure (HF) is increasing in patients with type 2
      diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk
      of developing HF that requires hospitalization. Such an increased risk has been
      consistently reported with thiazolidinediones (glitazones) and perhaps also with
      the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI
      53), whereas a markedly decreased risk was highlighted with the sodium - glucose
      cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME. Yet,
      the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on myocardial
      function remain controversial. Whereas some promising observations have been
      reported in various animal models, the effects of GLP-1RAs on myocardial function
      in humans are more heterogeneous, while the positive effect on left ventricular
      ejection fraction (LVEF), if any, appears to be inconsistent and rather modest in
      most patients with HF. However, no increased risk of hospitalization for HF has
      been reported with GLP-1RAs in meta-analyses of phase-II/III trials (exenatide,
      albiglutide, dulaglutide, liraglutide), demonstrating the safety of this
      pharmacological class, and such findings have been confirmed by three large
      prospective cardiovascular outcome trials (ELIXA with lixisenatide, LEADER with
      liraglutide and SUSTAIN-6 with semaglutide). In particular, LEADER reported a
      trend towards a reduction in HF hospitalization (-13%, P = 0.14), together with a
      significant reduction in cardiovascular and all-cause mortality in patients with
      T2D at risk of cardiovascular disease. These results are reassuring in the face
      of the somewhat negative results of the FIGHT trial, which evaluated the effects
      of liraglutide in patients with advanced HF and low LVEF, such that further
      studies and caution are now required when using this agent to treat such patients
      in clinical practice.

PMID- 28431667
TI  - The potential and pitfalls of GLP-1 receptor agonists for renal protection in
      type 2 diabetes.
AB  - Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits
      for the management of glucose levels in type 2 diabetes. In addition, recent data
      from clinical trials have demonstrated that treatment with Glucagon-Like Peptide
      1 Receptor agonists (GLP-1 RA) are also able to reduce new onset
      macroalbuminuria. These benefits may be consistent with the known effects of GLP
      1 RA on traditional risk factors for progressive kidney disease including glucose
      lowering, blood pressure lowering, reduced insulin levels and weight reduction.
      However, emerging evidence suggests that GLP-1 RA can also have direct effects in
      the kidney, including inhibiting NHE3-dependent sodium reabsorption in the
      proximal tubule. Additional effects on the intrarenal renin angiotensin system,
      ischaemia/hypoxia, inflammation, apoptosis and neural signalling may also
      contribute to renal benefits. The extent to which these effects are mediated by
      the GLP-1R remains to be established. Recent studies confirm that the metabolic
      products of GLP-1 retain important antioxidant and anti-apoptotic activities that
      are GLP-1 R independent. Moreover the divergent peptide sequences of the
      currently available GLP-1 RA may mean that divergent reno-protective efficacy
      could be anticipated from different GLP-1 RA on this basis. Kidney disease is an
      important and deadly clinical outcome, and one worth preventing. Although both
      experimental and clinical data now support the possibility of renoprotective
      effects arising from treatment with GLP-1 RA, further work is needed to optimise
      these effects. A logical synergism with SGLT2 inhibition also exists, and at
      least in the short term, this combination approach may become the most useful way
      to protect the kidney in type 2 diabetes.

PMID- 28431668
TI  - GLP-1 receptor agonists in NAFLD.
AB  - Non-alcoholic fatty liver disease (NAFLD) is very common in patients with type 2
      diabetes (T2D), with approximately two-thirds having a diagnosis of the disease.
      Currently, the only validated treatment for NAFLD is weight loss. A number of
      studies of animal models and human trials have evaluated the effects of glucagon
      like peptide-1 receptor agonists (GLP-1RAs) on liver fat content and suggest that
      the treatment could represent a new alternative for NAFLD management. In this
      review, our focus is on the main studies regarding the effects of GLP-1RAs on
      NAFLD. Also, the mechanisms that might explain their beneficial effects on liver
      diseases are analyzed.

PMID- 28431669
TI  - After the LEADER trial and SUSTAIN-6, how do we explain the cardiovascular
      benefits of some GLP-1 receptor agonists?
AB  - Recent cardiovascular outcome trials - the LEADER with liragutide and SUSTAIN-6
      with semaglutide - have shown significant reductions of major cardiovascular (CV)
      events with these glucagon-like peptide (GLP)-1 receptor agonists. Progressive
      separation of the treatment and placebo curves, starting clearly between 12 and
      18 months of the trial period, and significant reductions in the risk of
      myocardial infarction and stroke, indicate that the beneficial CV effects
      observed with GLP-1 receptor agonists could be due to an antiatherogenic effect.
      So far, the reasons for such an effect of GLP-1 receptor agonists have not been
      entirely clear, although several hypotheses may be proposed. As the reductions in
      glycated haemoglobin and systolic blood pressure (SBP) in these trials were
      modest, and both trials lasted only a short period of time, reductions in
      hyperglycaemia and SBP are unlikely to be involved in the beneficial CV effects
      of GLP-1 receptor agonists. On the other hand, their effect on lipids and, in
      particular, the dramatic decrease in postprandial hypertriglyceridaemia may
      explain their beneficial CV actions. Reduction of body weight, including a
      significant decrease in visceral fat in patients using GLP-1 receptor agonists,
      may also have beneficial CV effects by reducing chronic proatherogenic
      inflammation. In addition, there are in-vitro data showing a direct anti
      inflammatory effect with these agents that could also be involved in their
      beneficial CV effects. Moreover, studies in humans have shown significant
      beneficial effects on ischaemic myocardium after a very short treatment period,
      suggesting a direct effect of GLP-1 receptor agonists on myocardium, although the
      precise mechanism remains unclear. Finally, as a reduction in insulin resistance
      has been associated with a decrease in CV risk, it cannot be ruled out that the
      lowering of insulin resistance induced by GLP-1 receptor agonists might also be
      involved in their beneficial CV actions.

PMID- 28431670
TI  - Use of GLP-1 receptor agonists for type 2 diabetes treatment intensification
      after basal insulin failure.
AB  - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are part of the
      armamentarium for the treatment of type 2 diabetes (T2D), although recent
      guidelines have mainly recommended their use on top of oral treatments when a
      single or combination of two or three oral hypoglycaemic agents has failed to
      lower HbA1c levels below the individualized target range. In such situations, the
      decision to use GLP-1RAs is mostly driven by their high level of efficacy, their
      effect on body weight balance and their safety considerations, such as low
      hypoglycaemic risk. According to the current guidelines, GLP-1RAs may also be
      used in T2D patients in addition to basal insulin, following specialist-care
      advice, in patients who are more severely obese or who may not have the capacity
      to handle the complexities of a multiple daily injection (MDI) insulin regimen.
      The present review looks at the scientific evaluations performed in this context
      as well as the clinical trials assessing the use of GLP-1RAs in combination with
      intensive insulin therapy as further step-up therapy.

PMID- 28431671
TI  - Where Are We Now? A Clinicians' Guide to the Use of Follow-On Insulin for
      Patients with Diabetes.
AB  - Insulin has been used as a standard treatment for patients with diabetes for
      almost 100 years. Over time, advances in insulin development have improved its
      pharmacologic properties. (Online access:
      http://courses.elseviercme.com/t2dm/666). Most recently, the US Food and Drug
      Administration approved a novel, follow-on basal insulin agent, with more
      expected to be commercially available in the near future. With the imminent
      availability of follow-on basal insulin agents, clinicians need to be aware of
      the potential benefits and concerns in order to facilitate informed decision
      making and to provide the best possible advice and guidance to their patients
      with diabetes. This program will review how follow-on insulin products are
      developed, manufactured, and receive regulatory approval; evaluate clinical trial
      data for new and emerging follow-on basal insulin agents; and provide practical
      information and guidance on how they may be incorporated into clinical practice.
      While it is unknown how follow-on basal insulins will affect patient outcomes,
      they have the potential to increase access to treatment among patients with
      diabetes and reduce healthcare costs.

PMID- 28431672
TI  - Corrigendum to 'Trends in Opioid Prescriptions Among Part D Medicare Recipients
      from 2007 to 2012' The American Journal of Medicine (2016) 129, 221.e21-221.e30.

PMID- 28431673
TI  - Errancy on Lyme Diagnosis.

PMID- 28431674
TI  - Dealing with Lyme Disease Treatment.

PMID- 28431675
TI  - The Reply.

PMID- 28431676
TI  - Electronic Stethoscope for Coronary Stenosis Detection.

PMID- 28431677
TI  - The Reply.

PMID- 28431678
TI  - Intravenous Formulation Considerations for Hyponatremia.

PMID- 28431679
TI  - The Reply.

PMID- 28431680
TI  - Two paradigms for religious representation: The physicist and the playground (a
      reply to Levy).
AB  - In an earlier issue, I argue (2014) that psychology and epistemology should
      distinguish religious credence from factual belief. These are distinct cognitive
      attitudes. Levy (2017) rejects this distinction, arguing that both religious and
      factual "beliefs" are subject to "shifting" on the basis of fluency and
      "intuitiveness." Levy's theory, however, (1) is out of keeping with much research
      in cognitive science of religion and (2) misrepresents the notion of factual
      belief employed in my theory. So his claims don't undermine my distinction. I
      conclude by suggesting some approaches to empirically testing our views.

PMID- 28431681
TI  - Big data analysis reveals the truth of lumbar fusion: gender differences.

PMID- 28431682
TI  - Why we fail, the long-term outcome of lumbar fusion in the Swedish Lumbar Spine
      Study.

PMID- 28431683
TI  - Spine registries generate patient benefit in the century of big data: Author
      response to: Big data analysis reveals the truth of lumbar fusion: gender
      differences.

PMID- 28431684
TI  - Attacking obesity-related diseases at the source - Is bariatric surgery the next
      wave in cancer prevention?

PMID- 28431685
TI  - GalR3 mediates galanin proliferative effects on postnatal hippocampal precursors.
AB  - Galanin, a neuropeptide co-released from noradrenergic and serotonergic
      projection neurons to the dentate gyrus, has recently emerged as an important
      mediator for signaling neuronal activity to the subgranular neurogenic stem cell
      niche supporting adult hippocampal neurogenesis. Galanin and its receptors appear
      to play key roles in depression-like behavior, and effects on hippocampal
      neurogenesis are relevant to pharmacological strategies for treating depression,
      which in part appear to rely on restoring altered neurogenesis. We previously
      demonstrated that the GalR2/3 receptor agonist Gal 2-11 is proliferative and
      proneurogenic for postnatal hippocampal progenitor cells; however, the specific
      receptor mediation remained to be identified. With the recent availability of
      M1145 (a specific GalR2 agonist), and SNAP 37889 (GalR3 specific antagonist), we
      extend our previous studies and show that while M1145 has no proliferative
      effect, the co-treatment of postnatal rat hippocampal progenitors with Gal 2-11
      and SNAP 37889 completely abolished the Gal 2-11 proliferative effects. Taken
      together, these results clearly demonstrate that GalR3 and not GalR2 is the
      specific receptor subtype that mediates the proliferative effects of galanin on
      hippocampal progenitor cells. These results implicate GALR3 in the mediation of
      galanin neurogenic effects and, potentially, its neurogenic anti-depressant
      effects.

PMID- 28431686
TI  - ADM guidance-Ceramics: all-ceramic multilayer interfaces in dentistry.
AB  - This guidance document describes the specific issues involved in dental
      multilayer ceramic systems. The material interactions with regard to specific
      thermal and mechanical properties are reviewed and the characteristics of dental
      tooth-shaped processing parameters (sintering, geometry, thickness ratio, etc.)
      are discussed. Several techniques for the measurement of bond quality and
      residual stresses are presented with a detailed discussion of advantages and
      disadvantages. In essence no single technique is able to describe adequately the
      all-ceramic interface. Invasive or semi-invasive methods have been shown to
      distort the information regarding the residual stress state while non-invasive
      methods are limited due to resolution, field of focus or working depth. This
      guidance document has endeavored to provide a scientific basis for future
      research aimed at characterizing the ceramic interface of dental restorations.
      Along with the methodological discussion it is seeking to provide an introduction
      and guidance to relatively inexperienced researchers.

PMID- 28431687
TI  - A rapid impregnation method for loading desired amounts of extractant on
      prepacked reversed-phase columns for high performance liquid chromatographic
      separation of metal ions.
AB  - A time-efficient impregnation method for loading extractant onto reversed-phase
      columns was developed, using di-(2-ethylhexyl) phosphoric acid (HDEHP) as a model
      extractant. The optimal loading conditions for the impregnation process of a
      standard analytical scale column was achieved by dissolving an appropriate amount
      of HDEHP (per void volume) in n-pentane, flushing the column with two void
      volumes (5mL) of impregnation solution and heating the column for a short time to
      remove the solvent. The process takes about one hour, a significant time
      reduction compared to commonly used impregnation methods (17-23h). The
      chromatographic traits for separation of the lighter lanthanides (La-Gd) using
      columns impregnated under different conditions were evaluated; heating for short
      period of time gave improved column performance most likely due to the presence
      of n-pentane in the pores of the support material. A linear relation was found
      (R2=0.9934) for the amount of HDEHP loaded as a function of HDEHP concentration
      in the impregnation solution. The coated amounts of HDEHP were in the range of
      0.29-2.25mmol per column by flushing with 5mL of impregnation solution containing
      0.3-5.0mmol of HDEHP per void volume. This 'flush-evaporate' impregnation method
      allowed for loading a pre-determined amount of extractant and produces very small
      amounts of organic waste. An overview of the various impregnation approaches
      previously used for extractant coating on prepacked columns and bulk support
      materials is also presented.

PMID- 28431688
TI  - Thermal desorption-Gas chromatographic methodology for the determination of
      residual solvents in mesoporous silica.
AB  - In this work, thermal desorption-gas chromatography-flame ionization detection
      (TD-GC-FID) was adapted to enable the determination of residual solvents (RS) in
      mesoporous silica (MPSi). MPSi is often utilized in various pharmaceutical
      formulations or drug delivery systems and the accurate determination of RS is an
      important part of pharmaceutical quality control. Seven commonly used solvents
      (methanol, ethanol, acetone, isopropanol, dichloromethane, tetrahydrofuran and
      hexafluoroisopropanol) were evaluated in combination with 3 types of MPSi having
      pore sizes of 2-3, 15 and 25nm. Validation results showed general recovery values
      >98% and good linearity over the concentration ranges studied. The limits of
      detection (LOD) and limits of quantification (LOQ) for the different solvents
      ranged from 0.03 to 0.08MUg and from 0.1 to 0.2MUg per tube, respectively.
      Verification of the accuracy of the TD method was investigated by using an
      alternative method based on complete dissolution of MPSi in hydrofluoric acid
      (HF) followed by full evaporation headspace-GC (HS-GC). The results obtained from
      both procedures were not statistically different (p>0.05) when applied to actual
      experimental drug samples consisting of itraconazole loaded on MPSi.

PMID- 28431689
TI  - [Behavioral activation programs: A tool for treating depression efficiently].
AB  - INTRODUCTION: Major depressive disorder (MDD) is a debilitating disorder, and its
      treatment often requires complex and costly psychological therapies. Behavioral
      activation (BA) is a simple, effective and affordable psychotherapy recommended
      in the treatment of MDD. OBJECTIVES: (i) Explain the theoretical basis of BA and
      its application in clinical practice. (ii) Review the randomized controlled
      trials examining BA as a treatment for MDD through a systematic search of the
      existing literature. METHODS: Medline and ClinicalTrials databases were searched
      with the following keywords: ("behavioral activation" OR "behavioural
      activation") AND ("therapy" OR "psychotherapy"). (i) Articles describing BA's
      theoretical foundations and principles of therapy were selected. (ii) Randomized
      controlled trials studying BA as a treatment for depression were selected
      according to the PRISMA criteria. RESULTS: (i) BA is a behavioral therapy that
      helps patients to increase their behaviors towards rewarding and/or pleasant
      activities, and to decrease avoidant behaviors maintaining negative affects by
      negative reinforcement. BA also tends to increase behaviors towards life-goals
      used as positive reinforcement contingencies. BA is a brief and cost effective
      therapy, which can be evaluated by specific psychometric scales. (ii) BA has a
      strong therapeutic effect in MDD as evaluated by several randomized controlled
      trials of good quality. CONCLUSION: BA is a simple, affordable and effective
      treatment for MDD. Data is insufficient to provide proof for the interest of
      using commitment to life-goals as reinforcement contingencies. Behavioral
      inhibition is encountered amongst several psychiatric disorders and more studies
      should be conducted to discuss its use for other diseases such as schizophrenia
      or anxiety disorders.

PMID- 28431691
TI  - Sensorimotor activity measured via oscillations of EEG mu rhythms in speech and
      non-speech discrimination tasks with and without segmentation demands.
AB  - Better understanding of the role of sensorimotor processing in speech and non
      speech segmentation can be achieved with more temporally precise measures. Twenty
      adults made same/different discriminations of speech and non-speech stimuli
      pairs, with and without segmentation demands. Independent component analysis of
      64-channel EEG data revealed clear sensorimotor mu components, with
      characteristic alpha and beta peaks, localized to premotor regions in 70% of
      participants.Time-frequency analyses of mu components from accurate trials showed
      that (1) segmentation tasks elicited greater event-related synchronization
      immediately following offset of the first stimulus, suggestive of inhibitory
      activity; (2) strong late event-related desynchronization in all conditions,
      suggesting that working memory/covert replay contributed substantially to
      sensorimotor activity in all conditions; (3) stronger beta desynchronization in
      speech versus non-speech stimuli during stimulus presentation, suggesting
      stronger auditory-motor transforms for speech versus non-speech stimuli. Findings
      support the continued use of oscillatory approaches for helping understand
      segmentation and other cognitive tasks.

PMID- 28431690
TI  - Elevated Hemi-diaphragms as a Cause of ST-segment Elevation: A case report and
      review of literature.
AB  - While ST-segment elevation (STE) on ECG is widely recognized as representing
      myocardial infarction or injury such as coronary occlusion or pericarditis, STE
      may occasionally ensue from non-cardiac etiologies. Indeed, gastrointestinal
      disorders causing STE are not well documented in the literature. We present a
      case wherein extreme abdominal distension and hemi-diaphragm elevation resulted
      in extrinsic cardiac and epicardial coronary compression manifesting as STE.
      Subsequent relief of the abdominal distension resulted in resolution of STE
      representing a noncoronary cause of STE. A brief literature review, illustrating
      the importance of considering abdominal etiologies as a cause of STE is provided.

PMID- 28431692
TI  - Pleurectomy and Decortication: How I Teach It.

PMID- 28431694
TI  - Invited Commentary.

PMID- 28431693
TI  - The Society of Thoracic Surgeons General Thoracic Surgery Database 2017 Update on
      Outcomes and Quality.
AB  - The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) is
      a voluntary effort that provides participants with risk-adjusted semiannual
      performance reports that allow comparison of institutional outcomes against
      national benchmarks. With nearly 1,000 surgeons contributing data from more than
      300 centers across North America, the STS GTSD now includes almost a half million
      cases. In 2016, updated risk models for lung resection and esophagectomy for
      cancer were reported, and composite quality measures for lobectomy and
      esophagectomy were developed. Ongoing efforts include upgrading the STS GTSD,
      establishing public reporting of lobectomy for lung cancer composite scores,
      creating an on-line dashboard, and strengthening international collaboration with
      the European Society of Thoracic Surgery Registry. With these initiatives, the
      STS GTSD aims to continue to improve quality of care and support research
      endeavors in general thoracic surgery. This article summarizes current aggregate
      national outcomes in general thoracic surgery and reviews related activities in
      the areas of quality measurement, performance improvement, and transparency from
      the STS GTSD during the past 12 months.

PMID- 28431695
TI  - Invited Commentary.

PMID- 28431696
TI  - Invited Commentary.

PMID- 28431697
TI  - Invited Commentary.

PMID- 28431698
TI  - Invited Commentary.

PMID- 28431699
TI  - Denton A. Cooley, August 22, 1920, to November 18, 2016.
AB  - The world lost a medical trailblazer and inspirational humanitarian with the
      passing of Denton A. Cooley on November 18, 2016. The 28th president of The
      Society of Thoracic Surgeons, Cooley was an icon of the astounding progress of
      cardiovascular medicine in the 20th century and a visionary pioneer who shaped
      modern surgery.

PMID- 28431700
TI  - Fluorescent Identification of Sympathetic Ganglia During Thoracoscopy.

PMID- 28431701
TI  - Reply.

PMID- 28431702
TI  - Fifth Aortic Arch: Emperor's New Clothes?

PMID- 28431703
TI  - Regarding Surgical Anatomy of the Aortic Annulus.

PMID- 28431704
TI  - Reply.

PMID- 28431705
TI  - What Should Be the Systolic Cardiac Output in Aorta?

PMID- 28431706
TI  - Reply.

PMID- 28431707
TI  - Can Takosubo Syndrome in the Setting of Pericardiocentesis Be Prevented?

PMID- 28431708
TI  - Extramedullary Plasmacytoma Arising From the Anterior Mediastinum.
AB  - Plasmacytomas are a localized proliferation of plasma cells in the bone marrow
      and soft tissue. Extramedullary plasmacytomas are rare and typically solitary
      plasma cell neoplasms originating from extraosseous organs and tissues. A 31-year
      old woman was referred to our hospital with a rapidly growing abnormal shadow on
      a chest roentgenogram. Chest computed tomography showed that the lesion was
      located in the anterior mediastinum. She underwent surgery, and the tumor was
      diagnosed as an extramedullary plasmacytoma. She remains well 2 years
      postoperatively without recurrence. An extremely rare case of an anterior
      mediastinal extramedullary plasmacytoma is presented.

PMID- 28431709
TI  - Successful Single-Lung Transplantation in a Patient With a Lung Destroyed by
      Tuberculosis.
AB  - In most countries, patients with lungs destroyed by tuberculosis (TB) are
      excluded from lung transplantation (LTx) because of concerns about TB recurrence.
      LTx may be an effective therapeutic option for patients with chronic respiratory
      failure, but there are no reports of successful LTx in patients with lungs
      destroyed by TB. We present the case of successful single LTx in a patient with
      chronic respiratory failure after pneumonectomy with antituberculous
      chemotherapy. At the 16-month follow-up, he did not show any evidence of TB
      recurrence and his respiratory problems and quality of life were improved by LTx.

PMID- 28431710
TI  - Subacute Pericardial Tamponade After Sleeve Lower Lobectomy for an Extremely Rare
      Tumor.
AB  - A rare case of subacute cardiac tamponade developed in a 71-year-old patient
      after a left lower lobe sleeve lobectomy for cancer. The patient was successfully
      treated by drainage of the pericardial effusion by a pigtail catheter. The exact
      cause is uncertain, but it appears to include an inflammatory component.

PMID- 28431711
TI  - Nodular Fasciitis of the Posterior Chest Wall With Bone Invasion Mimicking a
      Malignant Neoplasm.
AB  - Nodular fasciitis is a self-limiting benign fibroblastic/myofibroblastic
      proliferation, which typically presents as a rapidly growing mass resembling an
      aggressive lesion clinically. It can also mimic a sarcoma histologically, hence
      the frequent characterization as "pseudosarcoma." We describe a case of a 53-year
      old man who presented with a posterior chest wall mass that on imaging showed
      erosion into the adjacent ribs. After resection, the diagnosis of nodular
      fasciitis was rendered. Bone erosion by nodular fasciitis is extremely rare and
      can resemble a malignant neoplasm radiologically.

PMID- 28431713
TI  - Mediastinal Paraganglioma.
AB  - Paragangliomas of the mediastinum are rare, with only approximately 150 cases
      reported in the literature. Surgical excision is the treatment of choice;
      however, these tumors often lie near critical vascular structures. Here we
      present the case of a patient with a mediastinal paraganglioma discovered during
      a diagnostic procedure.

PMID- 28431712
TI  - Salvage Operation in Case of Oligometastatic Disease.
AB  - In general, prognosis of stage IV non-small cell lung cancer is poor, and
      treatment is mostly palliative. However, oligometastatic disease is currently
      recognized as a specific entity with a better prognosis. We report a patient
      where combined chemoradiotherapy and salvage surgery led to extraordinary long
      term survival.

PMID- 28431714
TI  - Solitary Fibrous Tumor of the Pleura With Abdominal Aortic Blood Supply.
AB  - A solitary fibrous tumor of the pleura (SFTP) presenting with an aberrant
      arterial supply from the abdominal aorta is extremely rare, and it may be
      difficult to distinguish from intralobar sequestration (ILS). We report the case
      of a 38-year-old woman who presented with acute chest pain and was subsequently
      found to have a 17.5-cm intrathoracic mass. After preoperative arterial
      embolization of its feeding vessel, this presumed ILS was resected. However, the
      intraoperative findings revealed a benign SFTP. Here we discuss a unique
      presentation of a large SFTP radiographically mimicking an ILS, and we propose a
      safe management strategy for this entity.

PMID- 28431715
TI  - Tuberculous Empyema Post Bilateral Lung Transplant.
AB  - Tuberculous empyema in lung transplantation recipients is a rare entity, with
      only a handful of cases reported in the English-language literature. We are
      reporting a case of tuberculous empyema 3 months after uncomplicated bilateral
      lung transplantation. The recipient underwent video-assisted thoracic surgery for
      diagnosis and decortication. Both the recipient and donor lacked a history of
      tuberculosis or tuberculosis exposure.

PMID- 28431716
TI  - Invasive Medullary Type A Thymoma With Recurrent Distant Metastases.
AB  - Thymomas are rare epithelial mediastinal tumors showing a certain propensity for
      local and intrathoracic recurrences. Otherwise, extrathoracic metastases are very
      rarely reported and are usually associated with type B thymomas or thymic
      carcinomas. We present a challenging patient with an invasive (Masaoka-Koga stage
      IIb) medullary type A thymoma with recurrent extrathoracic metastases (pulmonary
      and vertebral localizations occurring 2 and 7 years after the initial radical
      thymectomy, respectively). Despite type A thymoma being considered a low-grade
      malignancy with a scarce propensity to recurrence, the present case should alert
      clinicians to the possibility of bone metastasis. Long-term follow-up in this
      slow-growing neoplasm is then mandatory.

PMID- 28431717
TI  - Chronic Periaortitis of Ascending Aorta With Bilateral Ostial Coronary Stenosis
      in a Young Female.
AB  - An 18-year-old woman without any risk factors for coronary artery disease or
      systemic vasculitis and infection presented with recurrent angina at rest.
      Coronary angiography revealed 100% occlusion of the ostial left main coronary
      artery and severe ostial right coronary artery stenosis. She underwent successful
      coronary artery bypass graft surgery. At surgery, the external surface of the
      ascending aorta was covered with a soft-tissue thickened mass; histopathology of
      the mass revealed chronic nonspecific inflammatory aortitis.

PMID- 28431718
TI  - Coronary Artery Bypass Grafting in a Patient With Polyarteritis Nodosa.
AB  - A 38-year-old man with polyarteritis nodosa presented with exertional chest pain.
      Coronary angiography revealed 3-vessel coronary artery disease. We performed 2
      vessel coronary artery bypass grafting with the saphenous vein because the left
      internal thoracic artery was in poor condition. Histological examination of the
      left internal thoracic artery showed a strong effect of polyarteritis nodosa.

PMID- 28431719
TI  - Mitral Valve Necrosis After Cardiac Surgery Using Gelatin-Resorcinol-Formaldehyde
      Glue.
AB  - We present a rare case of mitral regurgitation with anterior mitral leaflet
      perforation associated with gelatin-resorcinol-formaldehyde (GRF) glue. We
      performed mitral valve replacement for anterior mitral leaflet perforation
      occurred 7 years after aortic valve replacement and abscess cavity repair using
      GRF glue. Long-term follow-up is needed for patients who have undergone surgeries
      using GRF glue or BioGlue (CryoLife, Inc, Kennesaw, GA) because of the
      possibility of late complications. In particular, when an eccentric mitral
      regurgitation is observed after aortic root surgery using GRF glue or BioGlue,
      anterior mitral leaflet perforation should be considered.

PMID- 28431720
TI  - Hybrid Endovascular Repair of a Right-Sided Thoracoabdominal Aortic Aneurysm.
AB  - A right-sided thoracoabdominal aortic aneurysm involving a right-sided aortic
      arch is extremely rare. Surgical treatment for a right-sided thoracoabdominal
      aortic aneurysm is challenging due to the anatomical complexity. We report a case
      of a right-sided thoracoabdominal aortic aneurysm with a right-sided aortic arch
      successfully treated by hybrid visceral debranching and endovascular repair.

PMID- 28431721
TI  - Intra-Aortic Missile After Gunshot Wound to Chest: An Interesting Case of
      Traumatic Cardiac Injury.
AB  - Missile embolus to the heart, although uncommon, is one of the most challenging
      scenarios in trauma. We describe a 36-year-old man who presented with a gunshot
      wound to the left chest and a chest x-ray revealing a foreign body in the
      mediastinum. A median sternotomy was performed and an injury to the left
      ventricle was identified. After intraoperative echocardiography and fluoroscopy
      confirmed a foreign body in the aortic root, cardiopulmonary bypass was
      implemented. A bullet was retrieved from the noncoronary sinus of the aortic
      valve. Injuries to the anterior leaflet of the mitral valve and left ventricle
      were repaired.

PMID- 28431722
TI  - Rosai-Dorfman Disease of Right Atrium Mimicking Myxoma.
AB  - Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, is a
      rare multisystemic disorder that was first reported by Rosai and Dorfman in 1969.
      It is a distinct histioproliferative disorder due to overproduction of
      histiocytes, which accumulate in lymph nodes. The cardiac involvement of this
      disease is extremely rare, and until now, only 18 cases have been reported. We
      report the case of a 53-year-old woman with right atrial mass mimicking myxoma,
      which the histopathologic evaluation revealed to be Rosai-Dorfman disease of the
      right atrium.

PMID- 28431723
TI  - Successful Biventricular Conversion Late After Primary One and One-Half Ventricle
      Repair.
AB  - A 6-year-old girl with unbalanced atrioventricular septal defect, hypoplastic
      right ventricle, and severe common atrioventricular valve regurgitation developed
      patient-prosthetic mismatch. At 6 months old, she underwent primary one and one
      half ventricle repair and replacement of left side atrioventricular valve. A
      catheter examination showed that her right ventricular end-diastolic volume
      increased from 39.4 mL/m2 1 year after to 70 mL/m2 3.5 years after the previous
      surgery. Thus, at the timing of redo left side atrioventricular valve
      replacement, she was converted successfully to biventricular circulation. The
      postoperative course was uneventful, and the right atrial pressure was 7 mm Hg
      before discharge.

PMID- 28431724
TI  - Retrosternal Implantation of the Cardioverter-Defibrillator Lead in an Infant.
AB  - Using an implantable cardioverter-defibrillator (ICD) in small children is still
      challenging, but the need is increasing. We present a new approach to overcoming
      ICD problems caused by growth in infants. A redundant ICD lead was fixed to the
      superior border of the sternum and tunneled retrosternally to the subxiphoid
      region for connection to the generator, which was placed in a pocket beneath the
      left transversus abdominis muscle. The redundant retrosternal part of the lead
      straightened during growth, while cardiac coverage by the cardioversion energy
      field and the defibrillation vector were maintained appropriately.

PMID- 28431725
TI  - Intraoperative Three-Dimensional Mapping of Supraventricular Tachycardia in a
      Young Fontan Patient.
AB  - Preoperative tachycardia is uncommon before an initial Fontan procedure. Catheter
      intervention can risk complications in small patients. A patient with fetal
      tachycardia and double inlet left ventricle underwent Norwood and bidirectional
      Glenn procedures. She had persistent tachycardia. A three-dimensional
      electroanatomic mapping system was modified for the operative procedure; it was
      used to identify the arrhythmia substrate and cryoablate an atrioventricular
      nodal tachycardia. Mapping added 20 minutes to the operation. She is arrhythmia
      free and off medication after 4 months. This three-dimensional system was
      successfully adapted for an intraoperative SVT ablation in this small patient,
      and it may be useful in other settings.

PMID- 28431727
TI  - Pulmonary Venous Varix Presenting as a Pulmonary Nodule.

PMID- 28431726
TI  - Three-Dimensional Computed Tomography Helps Identify Muscles for Use in an
      Empyema Cavity.

PMID- 28431728
TI  - Mitral-Aortic Intervalvular Fibrosa Pseudoaneurysm Causing Systolic Compression
      of Left Main Trunk.

PMID- 28431729
TI  - Diagnosis of Aortic Dissection by a Subtle Wall Thickening in Transesophageal
      Echocardiography.

PMID- 28431730
TI  - A New Device of Needlescopic Thoracic Sympathectomy Through a Skin Incision.
AB  - We describe a new technique of performing sympathectomy with a new device. A
      single skin incision 3 mm long was made in the armpit. The device enables
      complete resection of the sympathetic segment through a single skin incision,
      whereas sympathectomy is limited by the use of the conventional needle technique.
      Even if sympathetic nerves and blood vessels were overlapping, separation of the
      two organs was performed safely. This device increases the possibility of
      planning surgical procedures for patients with difficult anatomies.

PMID- 28431731
TI  - Pericardial Conduit for Pulmonary Artery Reconstruction by Surgical Stapling.
AB  - Pulmonary artery reconstruction in lung cancer surgery is an effective surgical
      method to avoid pneumonectomy that leads to longer survival times with few
      adverse effects. The pericardium is often used for the interposition of a
      prosthetic conduit. A pericardial conduit can be easily and precisely constructed
      by surgical stapling, which facilitates pulmonary artery reconstruction. In this
      report, the process and pitfalls of surgical stapling are described.

PMID- 28431732
TI  - Retrograde Pulmonary Embolectomy for Acute Pulmonary Embolism: A Simplified
      Technique.
AB  - Surgical embolectomy in acute pulmonary embolism is usually reserved for patients
      with massive pulmonary embolism presenting with cardiogenic shock, or for whom
      thrombolysis is absolutely contraindicated or has failed. Incomplete removal of
      thrombotic material lodged in the distal pulmonary arterial bed is considered an
      important cause of persistent pulmonary hypertension. Retrograde pulmonary
      embolectomy is an adjunct to conventional pulmonary embolectomy, resulting in
      more complete embolectomy, specifically of material lodged in the distal
      pulmonary arterial bed. We describe our simplified technique of retrograde
      pulmonary embolectomy as a safe adjunct to conventional pulmonary embolectomy.

PMID- 28431733
TI  - Neonatal Repair of Persistent Fifth Aortic Arch Coarctation and Interrupted
      Fourth Aortic Arch.
AB  - Persistent left fifth aortic arch is a rare anomaly often associated with aortic
      coarctation. We report the case of a newborn presenting with signs of duct
      dependent aortic coarctation. Echocardiography showed an interrupted fourth
      aortic arch, persistent left fifth aortic arch associated with aortic
      coarctation, and a restrictive arterial duct. Arch repair was accomplished using
      the fifth aortic arch as an in situ flap to enlarge the hypoplastic fourth aortic
      arch associated with coarctectomy and extended end-to-end anastomosis. We believe
      that this newly reported surgical approach is safe and effective and allows for
      adequate enlargement of the entire fourth aortic arch.

PMID- 28431734
TI  - Gender and engineering aptitude: Is the color of science, technology,
      engineering, and math materials related to children's performance?
AB  - To investigate gender stereotypes, demonstrated engineering aptitude, and
      attitudes, children (N=105) solved an engineering problem using either pastel
      colored or primary-colored materials. Participants also evaluated the
      acceptability of denial of access to engineering materials based on gender and
      counter-stereotypic preferences (i.e., a boy who prefers pastel-colored
      materials). Whereas material color was not related to differences in female
      participants' performance, younger boys assigned to pastel materials demonstrated
      lower engineering aptitude than did other participants. In addition, results
      documented age- and gender-related differences; younger participants, and
      sometimes boys, exhibited less flexibility regarding gender stereotypes than did
      older and female participants. The findings suggest that attempts to enhance STEM
      (science, technology, engineering, and math) engagement or performance through
      the color of STEM materials may have unintended consequences.

PMID- 28431735
TI  - Characterization of an 'Amyloid Only' Transgenic (B6C3
      Tg(APPswe,PSEN1dE9)85Dbo/Mmjax) Mouse Model of Alzheimer's Disease.
AB  - The spatiotemporal pattern of cerebral amyloid deposition, detectable as light
      microscopically recognizable aggregates in an 'amyloid only' transgenic mouse
      model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported
      for the first time in this strain. Monoclonal and polyclonal antibodies were used
      to detect amyloid deposition immunohistochemically in brains collected from these
      mice at 3-12 months of age. Amyloid aggregates (20-200 MUm) were first found in
      serial, whole coronal sections of brain at 4 months of age and these increased
      progressively, plateauing at 11-12 months. They were most abundant in the
      cerebral cortices, hippocampus, olfactory bulbs, some white matter tracts and the
      cerebellar molecular layer; no amyloid aggregates were found in the midbrain,
      brainstem or spinal cord, or in an equivalent number of brains from wild-type
      mice. Since the parahippocampal gyrus is severely damaged early in the clinical
      course of human Alzheimer's disease, amyloid aggregates were also assessed in
      this brain region and a similar temporal course of amyloid deposition was
      observed. Moreover, in this gyrus, the amount of aggregated amyloid showed no
      significant difference between left- and right-sided gyri. However, the
      polyclonal antibody detected a significantly greater amyloid burden than the
      monoclonal antibody at 3-10 months of age and the reverse was seen at 11-12
      months of age. The pattern of amyloid deposition in the parahippocampal gyrus
      also resembled that found in the entire brain over time, when the latter was
      quantified by the colour deconvolution method, suggesting that this gyrus is a
      good marker for more widely distributed cerebral amyloid deposition. This
      neuropathological characterization will permit better use of the B6C3
      Tg(APPswe,PSEN1dE9)85Dbo/Mmjax transgenic mouse strain in future studies of
      Alzheimer's disease pathogenesis, prevention and treatment.

PMID- 28431736
TI  - Technical considerations about micro-ureteroscopy in children.

PMID- 28431737
TI  - Examining the dark recesses of the heart: Technology drives innovation.

PMID- 28431738
TI  - Aortic valve replacement in low-flow, low-gradient aortic stenosis: Left
      ventricular ejection fraction matters.

PMID- 28431739
TI  - Mitochondrial autotransplantation: A "shot" in the dark?

PMID- 28431740
TI  - Getting a grip on reality: Grasping movements directed to real objects and images
      rely on dissociable neural representations.
AB  - In the current era of touchscreen technology, humans commonly execute visually
      guided actions directed to two-dimensional (2D) images of objects. Although real,
      three-dimensional (3D), objects and images of the same objects share high degree
      of visual similarity, they differ fundamentally in the actions that can be
      performed on them. Indeed, previous behavioral studies have suggested that
      simulated grasping of images relies on different representations than actual
      grasping of real 3D objects. Yet the neural underpinnings of this phenomena have
      not been investigated. Here we used functional magnetic resonance imaging (fMRI)
      to investigate how brain activation patterns differed for grasping and reaching
      actions directed toward real 3D objects compared to images. Multivoxel Pattern
      Analysis (MVPA) revealed that the left anterior intraparietal sulcus (aIPS), a
      key region for visually guided grasping, discriminates between both the format in
      which objects were presented (real/image) and the motor task performed on them
      (grasping/reaching). Interestingly, during action planning, the representations
      of real 3D objects versus images differed more for grasping movements than
      reaching movements, likely because grasping real 3D objects involves fine-grained
      planning and anticipation of the consequences of a real interaction. Importantly,
      this dissociation was evident in the planning phase, before movement initiation,
      and was not found in any other regions, including motor and somatosensory
      cortices. This suggests that the dissociable representations in the left aIPS
      were not based on haptic, motor or proprioceptive feedback. Together, these
      findings provide novel evidence that actions, particularly grasping, are affected
      by the realness of the target objects during planning, perhaps because real
      targets require a more elaborate forward model based on visual cues to predict
      the consequences of real manipulation.

PMID- 28431742
TI  - The Sleeping Cerebellum.
AB  - We sleep almost one-third of our lives and sleep plays an important role in
      critical brain functions like memory formation and consolidation. The role of
      sleep in cerebellar processing, however, constitutes an enigma in the field of
      neuroscience; we know little about cerebellar sleep-physiology, cerebro
      cerebellar interactions during sleep, or the contributions of sleep to cerebellum
      dependent memory consolidation. Likewise, we do not understand why cerebellar
      malfunction can lead to changes in the sleep-wake cycle and sleep disorders. In
      this review, we evaluate how sleep and cerebellar processing may influence one
      another and highlight which scientific routes and technical approaches could be
      taken to uncover the mechanisms underlying these interactions.

PMID- 28431743
TI  - Opportunistic sampling to quantify plastics in the diet of unfledged Black Legged
      Kittiwakes (Rissa tridactyla), Northern Fulmars (Fulmarus glacialis) and Great
      Cormorants (Phalacrocorax carbo).
AB  - Seabirds can interact with marine litter, mainly by entanglement or ingestion.
      The ingestion of plastics can lead to starvation or physical damage to the
      digestive tract. For chicks, it could additionally lead to reduced growth,
      affecting survival and fledging. This study quantified the ingestion of plastics
      by seabird chicks via an opportunistic sampling strategy. When ringing is carried
      out at colonies, birds may spontaneously regurgitate their stomach contents due
      to the stress or as a defence mechanism. Regurgitates were collected from
      nestlings of three different species: Black-legged Kittiwake (Rissa tridactyla,
      n=38), Northern Fulmar (Fulmarus glacialis, n=14) and Great Cormorant
      (Phalacrocorax carbo, n=28). Plastic was present in all species, with the highest
      frequency of occurrence (FO) in Northern Fulmar chicks (28.6%), followed by Black
      legged Kittiwakes (7.9%) and Great Cormorants (7.1%). The observed load of
      plastics on chicks, which have not yet left the nest, highlights the pervasive
      nature of plastic pollution.

PMID- 28431744
TI  - Incidence of marine debris in seabirds feeding at different water depths.
AB  - Marine debris such as plastic fragments and fishing gears are accumulating in the
      ocean at alarming rates. This study assesses the incidence of debris in the
      gastrointestinal tracts of seabirds feeding at different depths and found
      stranded along the Brazilian coast in the period 2010-2013. More than half (55%)
      of the species analysed, corresponding to 16% of the total number of individuals,
      presented plastic particles in their gastrointestinal tracts. The incidence of
      debris was higher in birds feeding predominantly at intermediate (3-6m) and deep
      (20-100m) waters than those feeding at surface (<2m). These results suggest that
      studying the presence of debris in organisms mainly feeding at the ocean surface
      provides a limited view about the risks that this form of pollution has on marine
      life and highlight the ubiquitous and three-dimensional distribution of plastic
      in the oceans.

PMID- 28431741
TI  - Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with
      Therapeutic Potential.
AB  - Pharmacoresistant seizures and cytotoxic cerebral edema are serious complications
      of ischemic and traumatic brain injury. Intraneuronal Cl- concentration ([Cl-]i)
      regulation impacts on both cell volume homeostasis and Cl--permeable GABAA
      receptor-dependent membrane excitability. Understanding the pleiotropic molecular
      determinants of neuronal [Cl-]i - cytoplasmic impermeant anions, polyanionic
      extracellular matrix (ECM) glycoproteins, and plasmalemmal Cl- transporters -
      could help the identification of novel anticonvulsive and neuroprotective
      targets. The cation/Cl- cotransporters and ECM metalloproteinases may be
      particularly druggable targets for intervention. We establish here a paradigm
      that accounts for recent data regarding the complex regulatory mechanisms of
      neuronal [Cl-]i and how these mechanisms impact on neuronal volume and
      excitability. We propose approaches to modulate [Cl-]i that are relevant for two
      common clinical sequela of brain injury: edema and seizures.

PMID- 28431745
TI  - Mental health care in Athens: Are compulsory admissions in Greece a one-way road?
AB  - Involuntary hospitalization has long been a contentious issue worldwide. In
      Greece, the frequency of compulsory admissions is assumed to be alarmingly high;
      however, no study has systematically investigated this issue. In line with this,
      the present study aims to estimate the frequency of compulsory admissions in a
      psychiatric hospital and to explore its underpinnings. All individuals who were
      admitted to the Psychiatric Hospital of Attica during June-October 2011 were
      included into the study. Information about their socio-demographic and clinical
      characteristics as well as their previous contact with mental health services was
      obtained from interviewing the patient and his/her physician. Furthermore,
      information about the initiation of the process of compulsory admission as well
      as patient's referral upon discharge was retrieved from patients' administrative
      record. Out of the 946 admissions 57.4% were involuntary. A diagnosis of unipolar
      depression, high social support and previous contact with community mental health
      services were found to yield a protective effect against involuntary
      hospitalization. Moreover, 69.8% of civil detentions were instigated by close
      relatives and 30.2% ex officio. These two groups differed in patients' social
      support levels and in medication discontinuation being the reason for initiation
      of the process. Lastly, only 13.8% of patients were referred to community mental
      health services at discharge. Our findings suggest that civil detentions are
      deeply entrenched in clinical routine in Greece. Moreover, poor coordination
      among services and relatives' burden seem to contribute substantially to the
      elevated rates.

PMID- 28431746
TI  - Re-Evaluation of Serum Ferritin Cut-Off Values for the Diagnosis of Iron
      Deficiency in Children Aged 12-36 Months.
AB  - An ongoing challenge has been determining clinically relevant serum ferritin cut
      offs in the diagnosis of iron deficiency in children aged 1-3 years. We
      identified 2 potential clinically relevant serum ferritin cut-off values through
      their association with clinically important cut-off of hemoglobin as the
      indicator of anemia.

PMID- 28431747
TI  - Effects of vibration training in reducing risk of slip-related falls among young
      adults with obesity.
AB  - This study examined the effects of controlled whole-body vibration training on
      reducing risk of slip-related falls in people with obesity. Twenty-three young
      adults with obesity were randomly assigned into either the vibration or placebo
      group. The vibration and placebo groups respectively received 6-week vibration
      and placebo training on a side-alternating vibration platform. Before and after
      the training, the isometric knee extensors strength capacity was measured for the
      two groups. Both groups were also exposed to a standardized slip induced by a
      treadmill during gait prior to and following the training. Dynamic stability and
      fall incidences responding to the slip were also assessed. The results indicated
      that vibration training significantly increased the muscle strength and improved
      dynamic stability control at recovery touchdown after the slip occurrence. The
      improved dynamic stability could be resulted from the enhanced trunk segment
      movement control, which may be attributable to the strength increment caused by
      the vibration training. The decline of the fall rates from the pre-training slip
      to the post-training one was greater among the vibration group than the placebo
      group (45% vs. 25%). Vibration-based training could be a promising alternative or
      additional modality to active exercise-based fall prevention programs for people
      with obesity.

PMID- 28431748
TI  - A benchtop biorobotic platform for in vitro observation of muscle-tendon dynamics
      with parallel mechanical assistance from an elastic exoskeleton.
AB  - We present a novel biorobotic framework comprised of a biological muscle-tendon
      unit (MTU) mechanically coupled to a feedback controlled robotic environment
      simulation that mimics in vivo inertial/gravitational loading and mechanical
      assistance from a parallel elastic exoskeleton. Using this system, we applied
      select combinations of biological muscle activation (modulated with rate-coded
      direct neural stimulation) and parallel elastic assistance (applied via closed
      loop mechanical environment simulation) hypothesized to mimic human behavior
      based on previously published modeling studies. These conditions resulted in
      constant system-level force-length dynamics (i.e., stiffness), reduced biological
      loads, increased muscle excursion, and constant muscle average positive power
      output-all consistent with laboratory experiments on intact humans during
      exoskeleton assisted hopping. Mechanical assistance led to reduced estimated
      metabolic cost and MTU apparent efficiency, but increased apparent efficiency for
      the MTU+Exo system as a whole. Findings from this study suggest that the
      increased natural resonant frequency of the artificially stiffened MTU+Exo
      system, along with invariant movement frequencies, may underlie observed limits
      on the benefits of exoskeleton assistance. Our novel approach demonstrates that
      it is possible to capture the salient features of human locomotion with
      exoskeleton assistance in an isolated muscle-tendon preparation, and introduces a
      powerful new tool for detailed, direct examination of how assistive devices
      affect muscle-level neuromechanics and energetics.

PMID- 28431749
TI  - Pharmacological advances in the multimodal management of perioperative analgesia.
AB  - The concept of multimodal analgesia is currently widespread in our clinical
      practice. The aim of multimodal analgesia is to reduce the side effects derived
      from the drugs or techniques used for the control of pain together with greater
      effectiveness (combination of multiple mechanisms of action) with the maximum
      efficiency, that is, to combine different pharmacodynamics (synergistic or
      additive effects) and pharmacokinetics, in the context of a predictable acute
      pain model, thus allowing a prior strategy such as the model of acute
      postoperative pain. Pain is a complex physiological phenomenon. Postoperative
      pain involves multiple pathways including nociceptive, inflammatory, and
      neuropathic sources. In the transmission of pain therefore, different molecules
      participate, which means that there are multiple pharmacological targets on which
      to act, and therefore a wide range of drugs to be used following the physiology
      of pain.

PMID- 28431750
TI  - Opioid free general anesthesia: A paradigm shift?

PMID- 28431751
TI  - Neumopericardium in the course of laparoscopic myomectomy.

PMID- 28431752
TI  - Corrigendum to "Individualized relapse prediction: Personality measures and
      striatal and insular activity during reward-processing robustly predict relapse"
      [Drug and Alcohol Dependence 152 (2015) 93-101].

PMID- 28431753
TI  - eEF2K promotes progression and radioresistance of esophageal squamous cell
      carcinoma.
AB  - OBJECTIVES: To investigate the biological function of eEF2K in esophageal
      squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Tissue microarrays
      containing 100 pairs of ESCC tumor and adjacent normal tissues were completed.
      Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC
      cells. DNA damage, cell viability, migration and invasion, radioresistance,
      apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell
      assay, colony formation assay, flow cytometry and western blot, respectively.
      Tumor growth and radioresistance were also evaluated using xenograft models
      created in nude mice. RESULTS: eEF2K expression was higher in ESCC tissues
      compared with matched non-tumor tissues (P<0.05). Proliferation was increased in
      eEF2K overexpressing cells compared with controls (P<0.05), while silencing eEF2K
      reduced cell proliferation (P<0.05). Furthermore, lower levels of eEF2K
      expression correlated with slower migration and invasion rates (P<0.05), while
      higher levels of eEF2K expression with faster migration and invasion rates
      (P<0.05). eEF2K overexpression resulted in radioresistance and radiation-induced
      autophagy, and reduced radiation-induced apoptosis compared with controls, but
      silencing eEF2K promoted radiosensitivity and apoptosis, and reduced autophagy.
      In addition, eEF2K overexpression promoted the tumor growth in vivo (P<0.01).
      Combined treatment of NH125 (a pharmacological inhibitor of eEF2K) and radiation
      was more effective at delaying xenograft tumor growth than NH125 and radiation
      alone (P<0.05). CONCLUSION: eEF2K induced progression and radioresistance in
      ESCC, which may be a novel therapeutic target for ESCC to increase
      radiosensitivity.

PMID- 28431755
TI  - Fever induced by mesalazine.

PMID- 28431754
TI  - Effect of short-term DHEA supplementation on serum and hippocampal estrogen
      concentrations in perimenopausal female rhesus macaques.
AB  - The hippocampus of rhesus macaques expresses genes that encode key enzymes
      involved in the intracrine conversion of dehydroepiandrosterone (DHEA) to
      estradiol. Therefore, it is plausible that supplementary DHEA may enhance
      hippocampal estradiol concentrations and help to compensate for the marked
      postmenopausal attenuation of circulating estrogen levels. To test this
      hypothesis, we used LC-MS/MS to measure estradiol and estrone concentrations in
      the serum and hippocampus of young and old perimenopausal female rhesus macaques,
      as well as old perimenopausal females that received daily DHEA (5 mg) oral
      supplementation for 1 week. Despite lower concentrations of these estrogens in
      the serum of the older animals, their concentrations in the hippocampus did not
      show any obvious differences due to age or to DHEA supplementation. The results
      suggest that de novo estrogen synthesis in the brain may compensate for the
      perimenopausal loss of estrogens in the circulation even without supplemental
      DHEA.

PMID- 28431756
TI  - Plexiform fibromyxoma, a rare mesenchymal gastric tumor.

PMID- 28431757
TI  - Anti-ammonia treatment-responsive myoclonus as initial presentation of acquired
      hepatocerebral degeneration.

PMID- 28431758
TI  - Review of measurement techniques and methods for assessing personal exposure to
      airborne nanomaterials in workplaces.
AB  - Exposure to airborne agents needs to be assessed in the personal breathing zone
      by the use of personal measurement equipment. Specific measurement devices for
      assessing personal exposure to airborne nanomaterials have only become available
      in the recent years. They can be differentiated into direct-reading personal
      monitors and personal samplers that collect the airborne nanomaterials for
      subsequent analyses. This article presents a review of the available personal
      monitors and samplers and summarizes the available literature regarding their
      accuracy, comparability and field applicability. Due to the novelty of the
      instruments, the number of published studies is still relatively low. Where
      applicable, literature data is therefore complemented with published and
      unpublished results from the recently finished nanoIndEx project. The presented
      data show that the samplers and monitors are robust and ready for field use with
      sufficient accuracy and comparability. However, several limitations apply, e.g.
      regarding the particle size range of the personal monitors and their in general
      lower accuracy and comparability compared with their stationary counterparts. The
      decision whether a personal monitor or a personal sampler shall be preferred
      depends strongly on the question to tackle. In many cases, a combination of a
      personal monitor and a personal sampler may be the best choice to obtain
      conclusive results.

PMID- 28431759
TI  - A left handed surgeon's handicap: Technical note on the ambidextrous use of a
      Watson knife in burns surgery.

PMID- 28431760
TI  - [Are adjusted morbidity groups concordant with the clinical judgment of
      intervention in a chronic strategy?]

PMID- 28431761
TI  - [Dependent relative: Effects on family health].
AB  - OBJETIVES: The purpose of this work is to analyse the effects on informal
      caregiver's health and lifestyle when living with a dependent person at home. A
      comparison will be made between this situation and other situations involving
      commitment of time and energy, taking into account gender and age differences in
      each stage of the life cycle. DESIGN: Cross-sectional study analysing secondary
      data. SETTING: The method used for collecting information is the computer
      assisted personal interview carried out in selected homes by the Ministry of
      Health, Social Services and Equality. PARTICIPANTS: The study included 19,351
      participants aged over 25 years who completed the 2011-2012 Spanish National
      Health Survey. MAIN MEASUREMENTS: This research is based on demographic
      information obtained from a Spanish National Health Survey (2011/12). Using an
      empirical framework, the Logit model was select and the data reported as odds
      ratio. The estimations were repeated independently by sub-groups of age and
      gender. RESULTS: The study showed that the health of people who share their lives
      with a dependent person is worse than those who do not have any dependent person
      at home (they are 5 times at higher risk of developing health problems). The
      study found that being a woman, advance age, low educational level and does not
      work, also has an influence. Being a caregiver reduces the likelihood of
      maintaining a healthy lifestyle through physical exercise, relaxation, or eating
      a balanced diet. CONCLUSIONS: Living with a dependent person reduces the
      likelihood of maintaining healthy lifestyles and worsens the state of health of
      family members. Significant differences in gender and age were found.

PMID- 28431762
TI  - Effects of a common insecticide on wetland communities with varying quality of
      leaf litter inputs.
AB  - Chemical contamination of aquatic systems often co-occurs with dramatic changes
      in surrounding terrestrial vegetation. Plant leaf litter serves as a crucial
      resource input to many freshwater systems, and changes in litter species
      composition can alter the attributes of freshwater communities. However, little
      is known how variation in litter inputs interacts with chemical contaminants. We
      investigated the ecological effects resulting from changes in tree leaf litter
      inputs to freshwater communities, and how those changes might interact with the
      timing of insecticide contamination. Using the common insecticide malathion, we
      hypothesized that inputs of nutrient-rich and labile leaf litter (e.g., elm
      [Ulmus spp.] or maple [Acer spp.]) would reduce the negative effects of
      insecticides on wetland communities relative to inputs of recalcitrant litter
      (e.g., oak [Quercus spp.]). We exposed artificial wetland communities to a
      factorial combination of three litter species treatments (elm, maple, and oak)
      and four insecticide treatments (no insecticide, small weekly doses of 10 MUg L
      1, and either early or late large doses of 50 MUg L-1). Communities consisted of
      microbes, algae, snails, amphipods, zooplankton, and two species of tadpoles.
      After two months, we found that maple and elm litter generally induced greater
      primary and secondary production. Insecticides induced a reduction in the
      abundance of amphipods and some zooplankton species, and increased phytoplankton.
      In addition, we found interactive effects of litter species and insecticide
      treatments on amphibian responses, although specific effects depended on
      application regime. Specifically, with the addition of insecticide, elm and maple
      litter induced a reduction in gray tree frog survival, oak and elm litter delayed
      tree frog metamorphosis, and oak and maple litter reduced green frog tadpole
      mass. Our results suggest that attention to local forest composition, as well as
      the timing of pesticide application might help ameliorate the harmful effects of
      pesticides observed in freshwater systems.

PMID- 28431763
TI  - Immune response of the short neck clam Paphia malabarica to salinity stress using
      flow cytometry.
AB  - Paphia malabarica is a predominant and commercially important bivalve in India,
      persistently challenged by wavering salinity in a monsoon-influenced estuary. To
      examine the organism's immunological response under such a condition we
      challenged P. malabarica with different salinities (0, 5, 15, 25 and 35) for
      varied periods using a two-way experimental approach (in vitro and in vivo). This
      is the first study to report the response of P. malabarica hemocytes to salinity
      stress from a monsoon-influenced estuary on the southwest coast of India.
      Evaluation of total hemocytes count, mortality, lysosomal content, reactive
      oxygen species production, phagocytic and esterase activity was carried out using
      flow cytometric analysis. In both the experimental conditions, hemocyte
      parameters were significantly compromised at lower salinities (0 and 5) with an
      evident immuno-salinity tolerance range of 15-35. The damaging impact of 0 and 5
      salinities on hemocyte function intensified with a longer exposure period,
      indicating that prolonged exposure to low salinity could be detrimental to
      bivalve wellness if they are pushed beyond their tolerance range which is usually
      observed during the monsoon. Further studies should focus on the interactive
      effect of salinity tagged with different stressors influencing biology of P.
      malabarica.

PMID- 28431764
TI  - Seasonal monitoring of blue mussel (Mytilus spp.) populations in a harbor area: A
      focus on responses to environmental factors and chronic contamination.
AB  - Coastal waters corresponding to macrotidal systems are among the most variable
      marine biotopes. Sessile animals as bivalve mollusks may however be found forming
      intertidal beds at high densities, as allowed by full adaptation to local
      conditions. A better knowledge of adaptive responses to environmental factors is
      required to foresee possible adverse effects of global change. At the sub
      cellular level, transcriptional responses are among the earliest signals of
      environmental disturbances and they can reveal subtle and meaningful changes in
      organism exposed to stress. Three blue mussel (Mytilus spp.) populations
      inhabiting the Bay of Brest (France) in sites exposed to different levels of
      chronic pollution, from low to moderate, were surveyed upon a seasonal schedule,
      with special attention to the reproductive cycle. Major seawater parameters were
      monitored over a full-year in the framework of the S!RANO project, based on an
      automatic high frequency acquisition system installed aboard a ship of
      opportunity. The health status of mussels has been assessed by measuring a
      condition index and gametogenesis has been followed by histology. Selected
      biological responses to environmental stress were detected using a multimarker
      approach including expression of genes involved in chemical stress response and
      energetic metabolism, and cellular immune parameters. Environmental parameters
      showed deep seasonal variations which differed among sites. Most biological
      responses followed a seasonal pattern. Late winter and spring corresponded to an
      active reproduction period in the Bay of Brest. Earlier spawning was observed in
      harbor areas compared to the oceanic site and an altered physiological state was
      assumed in commercial harbor mussels during the reproductive period, suggesting
      that their health is compromised at this time of year. However, no signs of
      severe chemical stress were detected in both harbor mussel populations, which
      could reflect adaptive responses to adverse environmental conditions.

PMID- 28431765
TI  - Immune Modulation by Vitamin D: Special Emphasis on Its Role in Prevention and
      Treatment of Cancer.
AB  - PURPOSE: Vitamin D has been known to be involved in mineral and bone homeostasis
      for many years. In the past its main use was in treating osteoporosis and
      rickets. In recent years it was found that vitamin D is an immune-modulating
      agent and may also have a role in several diseases, including autoimmune
      diseases. The immune-modulating effects appear to be mediated by vitamin D
      interaction with the vitamin D receptor (VDR) that has transcriptional effects
      and is expressed on various cell types, especially those of the immune system.
      Immunologic and rheumatologic diseases were the first to be studied, but at the
      moment the spotlight is on the interactions between tumor cells and vitamin D.
      This review focuses on four forms of cancer that apparently benefit from a
      vitamin D supplementation during treatment: prostate, breast, and colorectal
      cancers and melanoma. Several studies reported that differences exist between
      white and black patients, which we discuss in the review. METHODS: We
      systematically searched PubMed for studies published in English. The search terms
      included vitamin D, cancer, breast, colorectal, prostate, and melanoma. FINDINGS
      AND IMPLICATIONS: Our findings show that vitamin D has the potential to become a
      valid coadjuvant in the treatment of cancer.

PMID- 28431766
TI  - Analysis of 2-Week Data from Two Randomized, Controlled Trials Conducted in
      Subjects with Frequent Heartburn Treated with Esomeprazole 20 mg.
AB  - PURPOSE: These secondary analyses used data from 2 similarly designed studies in
      subjects experiencing frequent heartburn to evaluate the efficacy of esomeprazole
      20 mg once daily for 2 weeks, which reflects the approved over-the-counter dosage
      and duration. METHODS: Subjects without endoscopically identified erosive
      esophagitis who were experiencing heartburn for >=6 months and >=4 of 7 days
      prior to baseline (study 1, N = 368; study 2, N = 349) were randomly assigned to
      receive double-blind treatment with esomeprazole 40 or 20 mg (administered as
      esomeprazole magnesium trihydrate 44.5 and 22.3 mg, respectively) or placebo once
      daily for 4 weeks. Subjects recorded the severity of heartburn in a daily diary,
      and investigators assessed subjects at each study visit. Two-week assessments
      were the primary end points of interest in these analyses and included the
      percentage of subjects with complete heartburn resolution (no episodes during 7
      consecutive days), time to sustained complete heartburn resolution (the first of
      7 consecutive episode-free days), and heartburn relief (no episodes other than
      <=1 mild episode during 7 consecutive days). FINDINGS: At week 2, the percentages
      of subjects who experienced complete heartburn resolution were significantly
      greater with esomeprazole 40 mg (study 1, 26.1%; study 2, 35.3%) and 20 mg (study
      1, 25.2%; study 2, 35.7%) compared with placebo (study 1, 9.0%; study 2, 3.4%)
      (all, P <= 0.001). Beginning on day 1, the percentages of subjects who
      experienced sustained heartburn resolution was significantly greater in the
      groups treated with esomeprazole 40 mg (study 1, 19%; study 2, 19%; P < 0.0001)
      and 20 mg (study 1, 10%; study 2, 15%; P < 0.05) compared with the group that
      received placebo (study 1, 2%; study 2, 1%). Additionally, at week 2, the
      percentages of subjects experiencing heartburn relief were significantly greater
      with esomeprazole 40 mg (study 1, 35.3%; study 2, 40.5%) and 20 mg (study 1,
      34.5%; study 2, 46.4%) compared with placebo (study 1, 16.5%; study 2, 8.6%)
      (all, P <= 0.001). IMPLICATIONS: The results of this study demonstrate that once
      daily treatment with esomeprazole 20 mg for 2 weeks effectively resolved
      subjects' heartburn compared with placebo, beginning on day 1. Studies precede
      FDA Act 801 clinical trial registration and results submission requirements.

PMID- 28431767
TI  - The New Drug Conditional Approval Process in China: Challenges and Opportunities.
AB  - PURPOSE: Our aim was to characterize the newly established new drug conditional
      approval process in China and discuss the challenges and opportunities with
      respect to new drug research and development and registration. METHODS: We
      examined the new approval program through literature review, law analysis, and
      data analysis. Data were derived from published materials, such as journal
      articles, government publications, press releases, and news articles, along with
      statistical data from INSIGHT-China Pharma Databases, the China Food and Drug
      Administration website, the Center for Drug Evaluation website, the US Food and
      Drug Administration website, and search results published by Google. FINDINGS:
      Currently, there is a large backlog of New Drug Applications in China, mainly
      because of the prolonged review time at the China Food and Drug Administration,
      resulting in a lag in drug approvals. In 2015, the Chinese government implemented
      the drug review and registration system reform and tackled this issue through
      various approaches, such as setting up a drug review fee system, adjusting the
      drug registration classification, and establishing innovative review pathways,
      including the conditional approval process. IMPLICATIONS: In Europe and the
      United States, programs comparable to the conditional approval program in China
      have been well developed. The conditional approval program recently established
      in China is an expedited new drug approval process that is expected to affect new
      drug development at home and abroad and profoundly influence the public health
      and the pharmaceutical industry in China. Like any program in its initial stage,
      the conditional approval program is facing several challenges, including setting
      up a robust system, formatting new drug clinical research requirements, and
      improving the regulatory agency's function for drug review and approval. The
      program is expected to evolve and improve as part of the government mandate of
      the drug registration system reform.

PMID- 28431768
TI  - Is there room for luminal-basal urothelial cell population quantification?
AB  - PURPOSE: Three cell layers compose the urothelium: basal, intermediate and
      luminal ("umbrella cells") and different diseases might arise from different cell
      populations. The aim of this study is to analyze the quantification ability of
      such cell populations by using four different protocols. METHODS: Twenty male
      rats (Wistar) were randomized in four groups of five animals: scraping, enzymatic
      30, 45 and 60minutes. The cells were isolated, analyzed by flow cytometer and
      data processed by BD FACSDIVATM software. RESULTS: The urothelium was separated
      in two cell populations that are different in size and complexity. The group that
      showed more efficiency in cells dissociation and cells separation was enzymatic
      protocol 45minutes. CONCLUSIONS: Enzymatic protocol 45minutes was able to isolate
      urothelial cell populations and might be explored as potential prognostic tool,
      patient selection and therapeutic target in urothelial diseases. Future studies
      should validate the potential clinical application to the proposed rational of
      luminal-basal paradigm in the urothelial cancer as hope for individualized
      approach.

PMID- 28431769
TI  - Trends in admissions for chest pain after the introduction of high-sensitivity
      cardiac troponin T.
AB  - BACKGROUND: The aim was to describe temporal trends in admission rates for chest
      pain and patient outcomes after the clinical introduction of the high-sensitivity
      cardiac troponin T (hs-cTnT) assay. METHODS: We included all patients aged
      >25years presenting with chest pain to the emergency department (ED) at our
      hospital during 2011-2014. For each year, rates of admissions, coronary
      angiographies, and revascularizations were determined. After adjustment for
      confounders, hazard ratios (HR) with 95% confidence intervals (CI) were
      calculated for mortality or major adverse cardiac events (MACE) within 1year of
      the ED visit per year, using 2011 as referent. RESULTS: In total, 15,472 chest
      pain patients were accountable for 18,237 visits to the ED. The chest pain
      admission rate in 2011 was 44%; 2012, 39%; 2013, 33%; and 2014, 28%, with an
      overall decrease in 36%. Coronary angiographies within 1year of the ED visit
      increased from 6.8% in 2011 to 9.6% in 2013, but the proportion of
      revascularizations was virtually unchanged. The risk of death within 1year of the
      visit increased by 51% (HR 1.51, 95% CI, 1.18-1.92) in 2014, compared with 2011.
      Only non-cardiovascular mortality was significantly increased (HR 1.85, 95% CI,
      1.34-2.55), with no increase in MACE. CONCLUSION: Admissions for chest pain were
      reduced by 36% the first 4years of hs-cTnT use. We observed no increase in MACE,
      but all-cause mortality increased significantly for non-cardiovascular causes
      only which was paralleled by a significant increase in the use of coronary
      angiographies.

PMID- 28431770
TI  - Aortic stenosis and non-cardiac surgery: A systematic review and meta-analysis.
AB  - BACKGROUND: Aortic stenosis (AS) poses a perioperative management dilemma to
      physicians looking after patients who require non-cardiac surgery. The objective
      of this review is to investigate mortality and adverse cardiovascular events in
      patients with and without AS who underwent non-cardiac surgery. METHODS: We
      searched MEDLINE and EMBASE for studies that evaluated mortality and adverse
      cardiovascular events in patients with and without AS who underwent non-cardiac
      surgery. Pooled risk ratios for mortality and adverse outcomes (myocardial
      infarction, stroke, heart failure, death) were calculated using the dichotomous
      analysis method and subgroup analysis was performed considering the effect of
      severity of AS and symptoms. RESULTS: We identified 9 relevant studies with
      29,327 participants. Among studies of severe AS, there was no significant
      difference in mortality (RR: 1.49, 95%CI:0.85-2.61; P=0.16) associated with non
      cardiac surgery, but there was a significant increase in the composite adverse
      outcome (RR: 2.30, 95%CI:1.33-3.97; P=0.003). When the analysis involved any
      other degree of AS, eight studies were included and the pooled results showed a
      significant increase in composite adverse outcome (RR: 1.64, 95%CI:1.23-2.19;
      P<0.001) and myocardial infarction (RR: 1.90, 95%CI:1.54-2.34; P<0.001). When
      patients with asymptomatic AS were considered, the pooled results of four studies
      suggested an increased risk of composite adverse outcomes (RR: 1.59, 95%CI:1.19
      2.12; P=0.002) but not mortality, myocardial infarction, heart failure or stroke.
      CONCLUSIONS: Patients with AS undergoing non-cardiac surgery have not been shown
      to be at increased risk of mortality, but have significantly higher rates of
      adverse cardiovascular events compared to patients without AS.

PMID- 28431771
TI  - Corrigendum to "Inflammation and immunogenicity limit the utility of the rabbit
      as a nonclinical species for ocular biologic therapeutics" [Regul. Toxicol.
      Pharmacol. (2017) 221-230].

PMID- 28431772
TI  - Low glycemic index treatment in patients with drug-resistant epilepsy.
AB  - OBJECTIVE: Low glycemic index treatment (LGIT) is a newly developed dietary
      therapeutic option for epilepsy that is less restrictive than the ketogenic diet
      (KD). Our objective was to determine the efficacy and tolerability of LGIT.
      METHODS: From March 2014 to February 2015, 36 patients received LGIT at Severance
      Children's Hospital. One-year seizure outcomes and side effects were evaluated.
      RESULTS: A total of 36 patients were assessed. Fourteen were female. Common
      diagnoses were Lennox-Gastaut syndrome (33%, 12/36) and Dravet syndrome (14%,
      5/36). The median age at the initiation of the LGIT was 12.6years (min.=1.5,
      max.=28, interquartile range (IQR) 8-17). After 3months of therapy, 20 (56%)
      patients experienced a 50% or greater reduction in seizure frequency, which was
      maintained in 19 (53%) patients for 1year. Two (6%) patients became seizure-free
      after 3months of LGIT; they remained seizure-free for 1year. These two had Dravet
      syndrome and generalized epilepsy. Only three (8%) patients discontinued
      treatment within 1year. Adverse events were rare, and two patients (6%) reported
      transient diarrhea. CONCLUSIONS: LGIT effectively reduced seizure frequency in
      the present study, although seizure freedom was infrequently achieved. LGIT may
      be considered as a therapeutic option for patients with drug-resistant epilepsy,
      particularly those who find KD effective but intolerable.

PMID- 28431773
TI  - Atypical moyamoya syndrome with brain calcification and stenosis of abdominal
      aorta and renal arteries.
AB  - Moyamoya syndrome is a progressive cerebrovascular disease that is characterized
      by stenosis of the terminal portion of the internal carotid artery and its main
      branches, in combination with an accompanying disease. We herein describe an 8
      year-old boy exhibiting transient loss of consciousness, who had recurrent
      seizures in infancy with progressive brain calcification. On admission, he was
      alert but magnetic resonance angiography showed bilateral stenosis of the whole
      internal carotid artery and proliferation of vascular collaterals, and brain CT
      revealed calcification on bilateral putamen. Given that this fulfilled diagnostic
      criteria, we finally diagnosed him as having moyamoya syndrome, though the
      etiology was unclear. Interestingly, a whole vessel survey revealed vascular
      stenosis of abdominal aorta and renal arteries, in which the former has not been
      reported in moyamoya syndrome. We considered that brain calcification was
      gradually formed by decreased cerebral vascular flow from infancy, and stenosis
      of abdominal aorta was possibly extended from renal arteries. This is, moyamoya
      syndrome with brain calcification and stenosis of abdominal aorta, suggesting
      that morphological screening of whole vessels containing cerebral and abdominal
      arteries should be considered in cases of slowly progressive brain calcification.

PMID- 28431774
TI  - Limited compensation at the following meal for protein and energy intake at a
      lunch meal in healthy free-living older adults.
AB  - Various interventions have previously been found to increase protein intakes in
      older adults, but in free-living individuals, compensation for increased intakes
      at one meal may easily negate these effects resulting in limited long term
      benefit. This study investigated the impact of adding sauce to an older person's
      lunch meal on intakes at that meal, at the following meal and overall (lunch +
      evening meal). Using a repeated measures design, 52 participants consumed both a
      lunch meal with sauce and the same lunch meal without sauce on two separate
      occasions, and intake at this meal and at the following meal were measured. In
      all participants analysed together, the addition of sauce resulted in increased
      protein intakes at the lunch meal. Individual differences were also found, where
      for some individuals (n = 26), the addition of sauce resulted in significantly
      higher protein and energy intakes at the lunch meal (12.3 g protein, 381 kJ) and
      overall (11 g protein, 420 kJ), compared to the no-sauce condition, while for
      some individuals (n = 19), the sauce manipulation resulted in lower protein and
      energy intakes (lunch: 7 g protein, 297 kJ; overall: 7 g protein, 350 kJ).
      Compensation for earlier intakes was low (0-17%) for both groups. These findings
      demonstrate the possible value of adding sauce to an older person's meal for
      increasing intakes, and demonstrate a need for attention to individual
      differences. This study also confirms previous findings of limited compensation
      in older adults, but extends earlier studies to demonstrate limited compensation
      for the protein consumed in a complete meal in healthy older adults.

PMID- 28431775
TI  - Cinacalcet Hydrochloride.
AB  - Cinacalcet hydrochloride is a calcimimetic agent that increases the sensitivity
      to the extracellular calcium of the calcium-sensing receptors of the parathyroid
      gland which regulates parathyroid hormone secretion. This comprehensive profile
      on cinacalcet hydrochloride starts with a description: nomenclature, formulae,
      chemical structure, elemental composition, and appearance. The uses and
      applications of the drug are included. The methods of preparation of cinacalcet
      hydrochloride are described and their respective schemes are outlined. The
      physical characterization of the drug is: ionization constant, solubility, X-ray
      powder diffraction (XRPD) pattern, crystal polymorphs, melting point, and
      differential scanning calorimetry. The spectral characteristics of the drug
      include: ultraviolet spectrum, vibrational spectrum, 1H and 13C nuclear magnetic
      resonance spectra, and the mass spectrum. The methods of analysis of the drug
      include: spectrophotometry, electrophoresis, fluorimetry, and high-performance
      liquid chromatography alone or with mass spectrometry. The stability of the drug
      in various media and storage conditions are reported. Biological studies on the
      drug include: the metabolism pharmacokinetics and pharmacodynamics. More than 100
      references are listed at the end of the chapter.

PMID- 28431776
TI  - Gliclazide.
AB  - Gliclazide is a second-generation oral hypoglycemic drug used for the treatment
      of noninsulin-dependent diabetes mellitus. It belongs to the sulfonylurea class
      that stimulates insulin secretion from pancreatic beta-cells by inhibiting ATP
      dependent potassium channels. Gliclazide also possesses unique antioxidant
      properties and other beneficial hemobiological effects. This profile represents a
      comprehensive description of the physical properties, chemical synthesis,
      spectroscopic characterization (FTIR, 1H NMR, 13C NMR, UV, and single-crystal X
      ray), methods of analysis, pharmacological actions, and pharmacokinetic and
      pharmacodynamic properties of the title drug.

PMID- 28431777
TI  - Lomefloxacin.
AB  - Lomefloxacin is a second-generation difluorinated broad-spectrum quinolone
      antibiotic. It is used for the treatment of bronchitis, urinary tract infection,
      conjunctivitis, otitis externa, and otitis media. A comprehensive profile was
      performed on lomefloxacin including nomenclature, formulae, elemental composition
      appearance, and physical characteristics. Spectral methods including ultraviolet
      spectrum, vibrational spectrum, 1H and 13C nuclear magnetic resonance one- and
      two-dimensional spectra, and mass spectrum were used for both identification and
      analysis of the drug. The profile also contains the reported methods of analysis
      such as voltammetric, polarographic, spectrophotometric, fluorimetric,
      chromatographic, capillary electrophoresis, and immunoassay methods. In addition,
      the uses, pharmacokinetics, and chemical synthesis of lomefloxacin are described.

PMID- 28431778
TI  - Olmesartan.
AB  - Olmesartan is an angiotensin receptor blockers with actions similar to those of
      losartan; it is used for the treatment of high blood pressure by relaxing blood
      vessels for this reason blood can flow more easily. It could be used alone or in
      combination with other antihypertensive drugs. This chapter gives a comprehensive
      profile of olmesartan, containing detailed nomenclature, formulae, elemental
      analysis, and appearance of the drug. In addition this chapter also describes
      several methods of synthesis and usage of the olmesartan. The profile covers the
      physicochemical properties including pKa value, solubility, X-ray powder
      diffraction, melting point, and procedures of analysis (compendial,
      spectroscopic, electrochemical, and chromatographic techniques of analysis).
      Comprehensive pharmacology is also presented (pharmacological actions,
      therapeutic uses and dosing, interactions, and adverse effects and precautions).
      Eighty references were given as a proof of the above-mentioned studies.

PMID- 28431779
TI  - Propranolol.
AB  - Propranolol is a noncardioselective beta-blocker. It is reported to have membrane
      stabilizing properties, but it does not own intrinsic sympathomimetic activity.
      Propranolol hydrochloride is used to control hypertension, pheochromocytoma,
      myocardial infarction, cardiac arrhythmias, angina pectoris, and hypertrophic
      cardiomyopathy. It is also used to control symptoms of sympathetic overactivity
      in the management of hyperthyroidism, anxiety disorders, and tremor. Other
      indications cover the prophylaxis of migraine and of upper gastrointestinal
      bleeding in patients with portal hypertension. This study provides a detailed,
      comprehensive profile of propranolol, including formulas, elemental analysis, and
      the appearance of the drug. In addition, the synthesis of the drug is described.
      The chapter covers the physicochemical properties, including X-ray powder
      diffraction, pK, solubility, melting point, and procedures of analysis
      (spectroscopic, electrochemical, and chromatographic). In-depth pharmacology is
      also presented (pharmacological actions, therapeutic dosing, uses, Interactions,
      and adverse effects and precautions). More than 60 references are given as a
      proof of the abovementioned studies.

PMID- 28431780
TI  - Tolterodine Tartrate.
AB  - Tolterodine tartrate belongs to the family of muscarinic receptor antagonists and
      is indicated for the treatment of overactive urinary bladder syndrome. This
      chapter provides an overview of physical, analytical, and ADME profiles;
      highlights methods of chemical synthesis; and discusses stability of tolterodine
      as a free base and/or its l-tartrate salt in solution and in the solid state. The
      information presented in this chapter is based on the peer-reviewed literature,
      compendial reports (USP, EP), and authors' data. Patent literature is included
      only in a few instances.

PMID- 28431781
TI  - Clenbuterol Hydrochloride.
AB  - Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with
      mainly beta-adrenergic activity and a selective action on beta2 receptors (a
      beta2 agonist). It has properties similar to those of salbutamol. It is used as a
      bronchodilator in the management of reversible airways obstruction, as in asthma
      and in certain patients with chronic obstructive pulmonary disease. The uses,
      applications, and the synthetic pathways of this drug are outlined. Physical
      characteristics including: ionization constant, solubility, X-ray powder
      diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass
      spectrum are all produced. This profile also includes the monograph of British
      Pharmacopoeia, together with several reported analytical methods including
      spectrophotometric, electrochemical, chromatographic, immunochemical methods, and
      capillary electrophoretic methods. The stability, the pharmacokinetic behavior,
      and the pharmacology of the drug are also provided.

PMID- 28431782
TI  - Preface to Volume 42.

PMID- 28431783
TI  - Supplementary Health Insurance from the consumer point of view: Are Israelis
      consumers doing an informed rational choice when purchasing Supplementary Health
      Insurance?
AB  - BACKGROUND: The National Health Insurance Law in Israel ensures basic health
      basket eligibility for all its citizens. A supplemental health insurance plan
      (SHIP) is offered for an additional fee. Over the years, the percentage of
      supplemental insurance's holders has risen considerably, ranking among the
      highest in OECD countries. The assumption that consumers implement an informed
      rational choice based on relevant information is doubtful. Are consumers
      sufficiently well informed to make market processes work well? OBJECTIVES: To
      examine perspectives, preferences and knowledge of Israelis in relation to SHIP.
      METHODOLOGY: A telephone survey was conducted with a representative sample of the
      Israeli adult population. 703 interviews were completed. The response rate was
      50.3%. FINDINGS: 85% of the sample reported possessing SHIP. This survey found
      that most of the Israeli public parched additional insurance coverage however did
      not show a significant knowledge about the benefits provided by the supplementary
      insurance, at least in the three measurements used in this study. CONCLUSIONS,
      POLICY IMPLICATIONS AND RECOMMENDATIONS: The scope of SHIP acquisition is very
      broad and cannot be explained in economic terms alone. Acquiring SHIP became a
      default option rather than an active decision. It is time to review the goals,
      achievements and side effects of SHIP and to create new policy for the future.

PMID- 28431784
TI  - Technical and instrumentational foundations of PET/MRI.
AB  - This paper highlights the origins of combined positron emission tomography (PET)
      and magnetic resonance imaging (MRI) whole-body systems that were first
      introduced for applications in humans in 2010. This text first covers basic
      aspects of each imaging modality before describing the technical and
      methodological challenges of combining PET and MRI within a single system. After
      several years of development, combined and even fully-integrated PET/MRI systems
      have become available and made their way into the clinic. This multi-modality
      imaging system lends itself to the advanced exploration of diseases to support
      personalized medicine in a long run. To that extent, this paper provides an
      introduction to PET/MRI methodology and important technical solutions.

PMID- 28431785
TI  - Multicausal etiology of the enteric syndrome in rabbits from Mexico.
AB  - Enteropathies in rabbits are difficult to diagnose; their etiology involves
      pathogens that act synergistically, causing damage to the intestine. The aim of
      the present study was isolate enteric pathogens from rabbits in Mexico. Using
      parasitological, bacteriological and molecular analyses, we screened 58 samples
      of the intestinal content of rabbits having a clinical history of enteric disease
      from the southeastern part of the State of Mexico. Out of the 58 samples
      analyzed, a total of 86 identifications were made, Eimeria spp. were found in
      77.5%, followed by Aeromonas spp. in 15.5% and Escherichia coli in 8.6%, which
      were identified as enteropathogenic E. coli (EPEC), and the presence of the
      following agents was also confirmed: Salmonella spp., Klebsiella spp.,
      Streptococcus spp., Staphylococcus aureus, Enterococcus spp., Mannheimia spp. and
      Rotavirus. The concurrent presence of Eimeria spp. with Aeromonas was frequent
      (15.5%); there was statistical significance for the presence of an association
      between the clinical profiles and Eimeria spp. (p=0.000), Mannheimia spp.
      (p=0.001), Salmonella spp., Klebsiella spp., Streptococcus spp. and Enterococcus
      spp. (p=0.006).

PMID- 28431786
TI  - [Ligninolytic enzyme production by white rot fungi during paraquat (herbicide)
      degradation].
AB  - Paraquat is a widely used herbicide in agriculture. Its inappropriate use and
      wide distribution represents a serious pollution problem for soil and water.
      White rot fungi are capable of degrading pollutants having a similar structure to
      that of lignin, such as paraquat. This study evaluated the degradation effect of
      paraquat on the production of ligninolytic enzymes by white rot fungi isolated
      from the South of Mexico. Six fungal strains showed tolerance to the herbicide in
      solid culture. Three of the six evaluated strains showed levels of degradation of
      32, 26 and 47% (Polyporus tricholoma, Cilindrobasidium laeve and Deconica
      citrispora, respectively) after twelve days of cultivation in the presence of the
      xenobiotic. An increase in laccase and manganese peroxidase (MnP) activities was
      detected in the strains showing the highest percentage of degradation.
      Experiments were done with enzyme extracts from the extracellular medium with the
      two strains showing more degradation potential and enzyme production. After
      24hours of incubation, a degradation of 49% of the initial paraquat concentration
      was observed for D. citrispora. These results suggest that paraquat degradation
      can be attributed to the presence of extracellular enzymes from white rot fungi.
      In this work the first evidence of the biodegradation potential of D. citrispora
      and Cilindrobasidium leave is shown.

PMID- 28431787
TI  - [Campylobacter jejuni O:19 serotype in Argentine poultry meat supply chain].
AB  - Thermotolerant species of Campylobacter have been focus of attention in the last
      years because they are the major agent causing zoonotic foodborne diseases. In
      addition, Campylobacter jejuni O:19 serotype was associated with Guillain Barre
      syndrome. The aim of this study was to determine the proportion of C. jejuni O:19
      serotype isolated at different stages of three poultry meat supply chain in Santa
      Fe, Argentina. The analysis showed that 18% of isolated C. jejuni belong to
      serotype O:19. It was also determined that the presence of these strains is given
      in almost all production stages. These results reflect a significant risk to
      public health of consumers. Epidemiological studies of Campylobacter should be
      considered to establish a risk manager policy.

PMID- 28431788
TI  - Morphology of the inferior border of the mandible: correct relation between the
      lowest position of the outer and inner contours of the cortex for a successful
      split.
AB  - For a sagittal split ramus osteotomy to be secure, the relation between the outer
      and inner contours of the cortex at the inferior border of the mandible is
      critical. The lowest point of the outer contour is not always immediately below
      that of the inner contour, and the former is placed more lingually than the
      latter in about a third of all cases. This tendency is much more noticeable in
      skeletal class I and II malocclusions than class III. It is therefore important
      to examine the lowest point of the inferior border in every case, and to carry
      the inferior part of the buccal cut on to the lingual side if necessary.

PMID- 28431789
TI  - [Thoracic involvement of multiple myeloma (MM) with light chains: Rare entity
      (about a case)].

PMID- 28431790
TI  - [Barriers to referral to pulmonary rehabilitation in COPD patients from the
      perspective of general practitioners].
AB  - INTRODUCTION: In spite of recommendations of the highest level of proof (rank A),
      the respiratory rehabilitation remains very widely sub-prescribed by general
      practitioners, who are nevertheless in the front line in the care and the follow
      up of the patients affected by BPCO. MATERIAL AND METHODS: Semi-qualitative study
      with the general practitioners installed in the city of Montauban (Tarn-et
      Garonne). RESULTS: The rate of answer was 57%. Eighty-six percent of the patients
      BPCO followed in general medicine have never participated in a respiratory
      rehabilitation program. Eighty percent of the questioned general practitioners
      declared not to know the last recommendations of the HAS. A total of 66.7% of the
      questioned general practitioners considered that prescription of respiratory
      rehabilitation comes within their remit. Eighty seven percent of the general
      practitioners declare not to know the existing respiratory programs of
      rehabilitation in their region. CONCLUSION: The main barrier for prescription of
      respiratory rehabilitation for patients BPCO in general medicine could be the
      misunderstanding of the local existing programs. The distribution of existing
      tools such as the map of the programs of respiratory rehabilitation established
      by the group Alveole of the Society of Pneumology of French language (SPLF) could
      so be a facilitating factor.

PMID- 28431791
TI  - Risk factors for noninvasive ventilation failure in patients with acute
      cardiogenic pulmonary edema: A prospective, observational cohort study.

PMID- 28431792
TI  - Changes to histone modifications following prenatal alcohol exposure: An emerging
      picture.
AB  - Epigenetic mechanisms are important for facilitating gene-environment
      interactions in many disease etiologies, including Fetal Alcohol Spectrum
      Disorders (FASD). Extensive research into the role of DNA methylation and miRNAs
      in animal models has illuminated the complex role of these mechanisms in FASD. In
      contrast, histone modifications have not been as well researched, due in part to
      being less stable than DNA methylation and less well-characterized in disease. It
      is now apparent that even changes in transient marks can have profound effects if
      they alter developmental trajectories. In addition, many histone methylations are
      now known to be relatively stable and can propagate themselves. As technologies
      and knowledge have advanced, a small group has investigated the role of histone
      modifications in FASD. Here, we synthesize the data on the effects of prenatal
      alcohol exposure (PAE) on histone modifications. Several key points are evident.
      AS with most alcohol-induced outcomes, timing and dosage differences yield
      variable effects. Nevertheless, these studies consistently find enrichment of
      H3K9ac, H3K27me2,3, and H3K9me2, and increased expression of histone
      acetyltransferases and methyltransferases. The consistency of these alterations
      may implicate them as key mechanisms underlying FASD. Histone modification
      changes do not often correlate with gene expression changes, though some
      important examples exist. Encouragingly, attempts to reproduce specific histone
      modification changes are very often successful. We comment on possible directions
      for future studies, focusing on further exploration of current trends, expansion
      of time-point and dosage regimes, and evaluation of biomarker potential.

PMID- 28431794
TI  - Challenging the addiction/health binary with assemblage thinking: An analysis of
      consumer accounts.
AB  - Critical analyses of drug use and 'addiction' have identified a series of binary
      oppositions between addiction and free will, independence, self-control,
      responsibility, productivity and autonomy. This critical work has also examined
      how science, policy and popular discourses frequently characterise addiction as
      antithetical to health and well-being. Furthermore, those diagnosed with
      addiction are often understood as indifferent to health and well-being, or as
      lacking the knowledge or desire required to maintain them. In this article, we
      draw on data from 60 qualitative interviews with people who self-identify as
      living with an 'addiction', 'dependence' or 'habit', to argue that the binary
      opposition between addiction and health struggles to attend to their rich and
      varied health perspectives and experiences. We explore three themes in the
      interview data: reinscribing the binary opposition between addiction and
      health/well-being; strategies for maintaining health and well-being alongside
      addiction; and alcohol and other drug consumption as aiding health and well
      being. Perhaps because addiction and health have been so thoroughly understood as
      antithetical, such perspectives and experiences have received surprisingly little
      research and policy attention. Yet they offer fertile ground for rethinking the
      strengths and capacities of those who self-identity as living with an addiction,
      dependence or habit, as well as untapped resources for responding to the harm
      sometimes associated with alcohol and other drug use.

PMID- 28431795
TI  - Shear Wave Liver Elastography with a Propagation Map: Diagnostic Performance and
      Inter-Observer Correlation for Hepatic Fibrosis in Chronic Hepatitis.
AB  - The aim of this study was to determine the performance of shear wave elastography
      (SWE) with a propagation map in the diagnosis of hepatic fibrosis, and to assess
      its reliability with transient elastography (TE) as the reference standard. Our
      prospective study included 115 consecutive patients with suspected or alleged
      chronic hepatitis. Patients underwent SWE by two different operators and TE by
      sonographers on the same day. The correlation coefficient of the intra-class
      correlation test between an experienced radiologist and a third-year radiology
      resident was 0.878. There was a moderate correlation between SWE and TE (r =
      0.511) in the diagnosis of hepatic fibrosis. The best cutoff values predicting
      significant hepatic fibrosis and liver cirrhosis by SWE were >1.78 m/s (area
      under the receiver operating characteristic curve [AUROC] = 0.777) and >2.24 m/s
      (AUROC = 0.935), respectively. SWE with a propagation map is a reliable method
      for predicting hepatic fibrosis regardless of operator experience.

PMID- 28431796
TI  - Lessons learned from twins in autoimmune and chronic inflammatory diseases.
AB  - Autoimmunity and chronic inflammation recognize numerous shared factors and, as a
      result, the resulting diseases frequently coexist in the same patients or respond
      to the same treatments. Among the convenient truths of autoimmune and chronic
      inflammatory diseases, there is now agreement that these are complex conditions
      in which the individual genetic predisposition provides a rate of heritability.
      The concordance rates in monozygotic and dizygotic twins allows to estimate the
      weight of the environment in determining disease susceptibility, despite recent
      data supporting that only a minority of immune markers depend on hereditary
      factors. Concordance rates in monozygotic and dizygotic twins should be evaluated
      over an observation period to minimize the risk of false negatives and this is
      well represented by type I diabetes mellitus. Further, concordance rates in
      monozygotic twins should be compared to those in dizygotic twins, which share 50%
      of their genes, as in regular siblings, but also young-age environmental factors.
      Twin studies have been extensively performed in several autoimmune conditions and
      cumulatively suggest that some diseases, i.e. celiac disease and psoriasis, are
      highly genetically determined, while rheumatoid arthritis or systemic sclerosis
      have a limited role for genetics. These observations are necessary to interpret
      data gathered by genome-wide association studies of polymorphisms and DNA
      methylation in MZ twins. New high-throughput technological platforms are awaited
      to provide new insights into the mechanisms of disease discordance in twins
      beyond strong associations such as those with HLA alleles.

PMID- 28431797
TI  - Video education for critical care nurses to assess pain with a behavioural pain
      assessment tool: A descriptive comparative study.
AB  - AIM: To evaluate the impact of video education on critical care nurses' knowledge
      and skills in using a behavioural pain assessment tool for intensive care
      patients and to explore the nurses' experiences with video education. METHODS:
      Forty-eight nurses in one intensive care unit watched an educational video on the
      use of the Critical-Care Pain Observation Tool, then assessed pain in two
      patients with the tool and took a knowledge test. The researcher made parallel
      pain assessments. Interrater reliability of patients' pain assessment between
      nurses and the researcher was determined to examine nurses' skills in using the
      tool after education. Twenty nurses were interviewed about their experiences with
      the video education. Interviews were analysed with deductive thematic analysis.
      RESULTS: The knowledge test scores indicated that the nurses learned the
      principles of how to use the tool. The interrater reliability of pain assessments
      reached a moderate level of agreement during the painful procedure, with a
      weighted kappa coefficient value of 0.48, CL [0.37, 0.58]. The nurses perceived
      video education positively, but requested additional interaction. CONCLUSIONS:
      Video education is useful in teaching the principles of using a pain assessment
      tool. Additional clinical training is required for nurses to reach adequate
      skills in using the tool.

PMID- 28431793
TI  - Alcohol effects on the epigenome in the germline: Role in the inheritance of
      alcohol-related pathology.
AB  - Excessive alcohol exposure has severe health consequences, and clinical and
      animal studies have demonstrated that disruptions in the epigenome of somatic
      cells, such as those in brain, are an important factor in the development of
      alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal
      alcohol spectrum disorders (FASDs). It is also well known that alcohol-related
      health problems are passed down across generations in human populations, but the
      complete mechanisms for this phenomenon are currently unknown. Recent studies in
      animal models have suggested that epigenetic factors are also responsible for the
      transmission of alcohol-related pathologies across generations. Alcohol exposure
      has been shown to induce changes in the epigenome of sperm of exposed male
      animals, and these epimutations are inherited in the offspring. This paper
      reviews evidence for multigenerational and transgenerational epigenetic
      inheritance of alcohol-related pathology through the germline. We also review the
      literature on the epigenetic effects of alcohol exposure on somatic cells in
      brain, and its contribution to AUDs and FASDs. We note gaps in knowledge in this
      field, such as the lack of clinical studies in human populations and the lack of
      data on epigenetic inheritance via the female germline, and we suggest future
      research directions.

PMID- 28431798
TI  - Absence of myoepithelial cells correlates with invasion and metastasis of
      Carcinoma ex pleomorphic adenoma.
AB  - Myoepithelial cells (MECs) are implicated in the development and progression of
      human salivary gland tumours. Here, we investigate the potential role for MECs in
      invasion and metastasis of carcinoma ex pleomorphic adenoma (CXPA). Tumour
      tissues from 40 CXPA patients diagnosed between 1960 and 2014 were obtained.
      Patient samples were divided into two groups (non-invasive tumours, n=10; and
      frankly invasive tumours, n=30). Each group was further divided into two
      subgroups (metastatic tumours and non-metastatic tumours). Immunohistochemistry
      for MEC markers (alpha-SMA, CALPONIN, and p63) was performed, and the number and
      distribution of MECs was quantified. For non-invasive CXPAs, non-metastatic cases
      (n=8) displayed a significant enrichment in CALPONIN(+) and alpha-SMA(+) MECs,
      but not p63(+) MECs, compared with metastatic cases (n=2). Likewise, for frankly
      invasive CXPAs (n=30), non-metastatic cases showed a significant enrichment for
      alpha-SMA(+), CALPONIN(+), and p63(+) MECs compared with metastatic cases (n=15).
      We demonstrate that non-invasive CXPAs have the potential for metastasis.
      Furthermore, the tumour capsule may not be the only barrier preventing invasion
      and metastasis, as a significant reduction in numbers of myoepithelial cells
      correlates with invasion and metastasis in CXPA patients.

PMID- 28431799
TI  - An MRI investigation of the effects of user anatomy and wheelchair cushion type
      on tissue deformation.
AB  - AIM OF THE STUDY: Tissue deformation is recognized as an important risk factor
      for pressure injuries. This study investigated the effects of anatomy and
      wheelchair cushion type on tissue deformation. MATERIALS AND METHODS: Direct 3
      dimensional tissue deformation response was measured for six participants sitting
      on six different wheelchair cushions using MR imaging. Two participants had a
      traumatic spinal cord injury (SCI) within one year of the assessment, two
      sustained traumatic SCI at least 13 years prior, and two were without SCI. Tissue
      deformation was quantified using the difference in volume of tissue beneath the
      ischial tuberosity (IT) between unloaded and loaded (sitting) conditions.
      RESULTS: The participants with SCI tended to have less muscle tissue volume
      beneath their ITs while sitting compared to participants without SCI. Reductions
      in muscle and fat volumes in the loaded conditions varied depending on both
      cushion and participant. Higher interface pressures tended to be associated with
      lower unloaded tissue thicknesses. CONCLUSION: The study showed no single cushion
      type tested produced the lowest amount of tissue deformation across all
      participants. Individual anatomy and cushion type affect deformation response of
      tissue and related pressure injury risk.

PMID- 28431801
TI  - Response to: Enucleation: A treatment alternative for branch duct intraductal
      papillary mucinous neoplasms.

PMID- 28431800
TI  - Genetic predictors of antipsychotic response to lurasidone identified in a genome
      wide association study and by schizophrenia risk genes.
AB  - Biomarkers which predict response to atypical antipsychotic drugs (AAPDs)
      increases their benefit/risk ratio. We sought to identify common variants in
      genes which predict response to lurasidone, an AAPD, by associating genome-wide
      association study (GWAS) data and changes (Delta) in Positive And Negative
      Syndrome Scale (PANSS) scores from two 6-week randomized, placebo-controlled
      trials of lurasidone in schizophrenia (SCZ) patients. We also included SCZ risk
      SNPs identified by the Psychiatric Genomics Consortium using a polygenic risk
      analysis. The top genomic loci, with uncorrected p<10-4, include: 1) synaptic
      adhesion (PTPRD, LRRC4C, NRXN1, ILIRAPL1, SLITRK1) and scaffolding (MAGI1, MAGI2,
      NBEA) genes, both essential for synaptic function; 2) other synaptic plasticity
      related genes (NRG1/3 and KALRN); 3) the neuron-specific RNA splicing regulator,
      RBFOX1; and 4) ion channel genes, e.g. KCNA10, KCNAB1, KCNK9 and CACNA2D3). Some
      genes predicted response for patients with both European and African Ancestries.
      We replicated some SNPs reported to predict response to other atypical APDs in
      other GWAS. Although none of the biomarkers reached genome-wide significance,
      many of the genes and associated pathways have previously been linked to SCZ. Two
      polygenic modeling approaches, GCTA-GREML and PLINK-Polygenic Risk Score,
      demonstrated that some risk genes related to neurodevelopment, synaptic biology,
      immune response, and histones, also contributed to prediction of response. The
      top hits predicting response to lurasidone did not predict improvement with
      placebo. This is the first evidence from clinical trials that SCZ risk SNPs are
      related to clinical response to an AAPD. These results need to be replicated in
      an independent sample.

PMID- 28431802
TI  - Threshold of number of rib fractures in elderly blunt trauma: A simple or complex
      matter of numbers?

PMID- 28431803
TI  - Reutilization of discarded biomass for preparing functional polymer materials.
AB  - Biomass is abundant and recyclable on the earth, which has been assigned numerous
      roles to human beings. However, over the past decades, accompanying with the
      rapid expansion of man-made materials, such as alloy, plastic, synthetic rubber
      and fiber, a great number of natural materials had been neglected and abandoned,
      such as straw, which cause a waste of resource and environmental pollution. In
      this review, based on introducing sources of discarded biomass, the main
      composition and polymer chains in discarded biomass materials, the traditional
      treatment and novel approach for reutilization of discarded biomass were
      summarized. The discarded biomass mainly come from plant wastes generated in the
      process of agriculture and forestry production and manufacturing processes,
      animal wastes generated in the process of animal husbandry and fishery production
      as well as the residual wastes produced in the process of food processing and
      rural living garbage. Compared with the traditional treatment including burning,
      landfill, feeding and fertilizer, the novel approach for reutilization of
      discarded biomass principally allotted to energy, ecology and polymer materials.
      The prepared functional materials covered in composite materials, biopolymer
      based adsorbent and flocculant, carrier materials, energy materials, smart
      polymer materials for medical and other intelligent polymer materials, which can
      effectively serve the environmental management and human life, such as wastewater
      treatment, catalyst, new energy, tissue engineering, drug controlled release, and
      coating. To sum up, the renewable and biodegradable discarded biomass resources
      play a vital role in the sustainable development of human society, as well as
      will be put more emphases in the future.

PMID- 28431804
TI  - Prognostic value of dynamic MRI positive enhancement integral color mapping in
      osteosynthesis of undisplaced femoral neck fractures.
AB  - AIMS: The common treatment for an undisplaced femoral neck fracture is
      osteosynthesis. Two major complications of osteosynthesis are non-union and late
      collapse of the femoral head. We speculated that femoral head perfusion is one of
      the most important factors that affect the outcome of osteosynthesis after
      femoral neck fracture. We have preoperatively estimated femoral head perfusion by
      dynamic MRI positive enhancement integral color mapping (PEICM). The purpose of
      this study was to evaluate the outcomes of undisplaced femoral neck fractures
      based on PEICM. PATIENTS AND METHODS: Sixty-eight patients participated in this
      prospective study. All patients underwent PEICM in a 1.5-Tesla MRI machine using
      coronal fast spoiled gradient echo imaging sequences with gadopentetate
      dimeglumine as the contrast agent. Femoral head perfusion was displayed via color
      mapping using PEICM. Three types were distinguished. For type A, the color was
      identical to unaffected side indicated normal perfusion. For type B, the color
      was darker than unaffected side indicated decreased perfusion. For type C, the
      color was black indicated complete absence of perfusion. All patients underwent
      osteosynthesis with three cannulated screws. The rates of non-union and late
      collapse for each type were calculated. RESULTS: Sixteen patients were classified
      as Type A, 43 as Type B, and 6 as Type C. The non-union rates were 0% for Type A,
      6.7% for Type B, and 50.0% for Type C. The late collapse rates were 0% for Type
      A, 4.4% for Type B, and 0% for Type C. CONCLUSION: PEICM precisely detected
      femoral head perfusion. Primary prosthetic replacement should be considered for
      older patients with Type C to minimize the chances of revision surgery, even in
      undisplaced femoral neck fractures.

PMID- 28431805
TI  - Lumbar disc degeneration progression in young women in their 20's: A prospective
      ten-year follow up.
AB  - BACKGROUND: Lumbar disc degeneration (LDD) is known to be the main cause of low
      back pain, although it is unclear how or when LDD progresses. The purpose of this
      study was to clarify the process and features of LDD progression in young women.
      METHODS: We enrolled 480 nursing students and carried out a prospective cohort
      study in 84 nursing students. MRI of the lumbar spine was taken once during their
      time as a student and again at 9.8 years (7-14) after the first MRI when they
      were working as nurses. The grade of LDD was determined according to
      Schneiderman's grade. The progression of disc degeneration was evaluated by the
      change in the degenerative disc disease (DDD) score (the summation of DDD score
      at each disc level). The subjects were divided into two groups based on MRI
      findings: Group A, those without disc degeneration at the first MRI (n = 58) and
      Group B, those showing disc degeneration on the first MRI (n = 26). We evaluated
      the change in DDD score and assessed the particular disc levels that showed
      Schneiderman's grade worsening in each group. RESULTS: At the time of the 2nd
      MRI, the DDD score increased from 5.6 (5-9) to 6.3 (5-11). The L5/S disc was the
      most frequent level showing the progression of LDD. In Group A, 18 subjects
      (31.0%) and in Group B, 15 subjects (57.7%) had degeneration progression (p =
      0.02). CONCLUSIONS: This study revealed that 31% of the young adult subjects
      already had disc degeneration in 20's (time of first MRI) and the disc
      degeneration rapidly progressed in these subjects.

PMID- 28431806
TI  - Gender-specific evaluation of variation of maxillary exposure when smiling.
AB  - INTRODUCTION: Excessive exposure of maxillary teeth when smiling can have a
      negative effect on the aesthetics and attractiveness of the face. The presented
      study was aimed to evaluate the effect of different amounts of gingival exposure
      on the perception of such human characteristics and qualities as age,
      attractiveness, gender specificity, and felt sympathy in the context of the whole
      face. MATERIALS AND METHODS: Forty-two participants (21 female and 21 male
      students of Dental Medicine) were recruited as evaluators for the study. Two
      average-looking subjects (one female, one male) were photographed. The images
      were processed to create a series of eight clones with different gingival
      exposure (shift A-H; A = full over-exposure, H = invisibility of the crown
      surfaces of the teeth). The panellists evaluated characteristics as
      attractiveness, gender specificity, age, and felt sympathy. RESULTS: 42
      participants joined the study (21 female, 21 male). Shift H was assessed as worst
      for sympathy and attractiveness, and resulted in the highest estimated age. Best
      attractiveness was observed for shifts C and D. Gender dimorphism was noticed,
      with own gender being rated as less attractive and opposite gender as more
      attractive. CONCLUSIONS: Female and male evaluators assess excessive gingival and
      maxillary incisor display differently for female and male probands. Excessive
      over- or underexposure of the maxillary gingiva and teeth when smiling is
      perceived as unattractive and results in less observer sympathy.

PMID- 28431807
TI  - Rhabdomyosarcoma of the maxillofacial region in children and adolescents: Report
      of 9 cases and literature review.
AB  - OBJECTIVE: To review clinical presentation, histology, treatment and survival for
      pediatric maxillofacial rhabdomyosarcoma (RMS) and evaluate the role of surgical
      treatment. STUDY DESIGN: Retrospective analysis of medical charts. METHODS: Files
      of patients, treated for primary maxillofacial RMS from 1997 to 2016, were
      examined for clinical presentation, staging, histology, treatment protocol and
      complications, recurrence and final outcome. RESULTS: Our cohort included 4 male
      and 5 female patients (mean age 8.47 years). One tumor, occupying the
      infratemporal space, was parameningeal; the other 8, located at the mandible (4)
      or the maxilla/zygomatic bone (4) were non-parameningeal. All patients received
      chemotherapy preoperatively. Surgery was performed in 7 patients, of whom 4
      received postoperative radiotherapy. The histological type was alveolar (5) or
      embryonal (4). Overall survival hitherto was 66,6%, depending on histology (40%
      and 100% for the alveolar and embryonal type respectively). CONCLUSIONS:
      Pediatric maxillofacial RMS originated mostly from the facial skeleton and most
      tumors were non-parameningeal. The alveolar type was slightly more common. An
      individualized multidisciplinary approach combining chemotherapy and local
      control mostly with surgery and selectively with radiotherapy has proven
      successful for the treatment of non-orbital, non-parameningeal maxillofacial RMS.
      Histology was a major treatment determinant and the most important prognostic
      factor.

PMID- 28431808
TI  - A Practical Standardized Composite Nutrition Score Based on Lean Tissue Index:
      Application in Nutrition Screening and Prediction of Outcome in Hemodialysis
      Population.
AB  - OBJECTIVE: Rapid screening and monitoring of nutritional status is mandatory in
      hemodialysis population because of the increasingly encountered nutritional
      problems. Considering the limitations of previous composite nutrition scores
      applied in this population, we tried to develop a standardized composite
      nutrition score (SCNS) using low lean tissue index as a marker of protein wasting
      to facilitate clinical screening and monitoring and to predict outcome. DESIGN
      AND METHODS: This retrospective cohort used 2 databases of dialysis populations
      from Taiwan between 2011 and 2014. First database consisting of data from 629
      maintenance hemodialysis patients was used to develop the SCNS and the second
      database containing data from 297 maintenance hemodialysis patients was used to
      validate this developed score. RESULTS: SCNS containing albumin, creatinine,
      potassium, and body mass index was developed from the first database using low
      lean tissue index as a marker of protein wasting. When applying this score in the
      original database, significantly higher risk of developing protein wasting was
      found for patients with lower SCNS (odds ratio 1.38 [middle tertile vs highest
      tertile, P < .0001] and 2.40 [lowest tertile vs middle tertile, P < .0001]). The
      risk of death was also shown to be higher for patients with lower SCNS (hazard
      ratio 4.45 [below median level vs above median level, P < .0001]). These results
      were validated in the second database. CONCLUSION: We developed an SCNS
      consisting of 4 easily available biochemical parameters. This kind of scoring
      system can be easily applied in different dialysis facilities for screening and
      monitoring of protein wasting. The wide application of body composition monitor
      in dialysis population will also facilitate the development of specific nutrition
      scoring model for individual facility.

PMID- 28431809
TI  - Pilot Study of Changes in Presepsin Concentrations Compared With Changes in
      Procalcitonin and C-Reactive Protein Concentrations After Cardiovascular Surgery.
AB  - OBJECTIVE: The authors investigated the presepsin-concentration profile after
      cardiac surgery compared with those of procalcitonin (PCT) and C-reactive protein
      (CRP). DESIGN: A single-center, prospective, observational clinical study.
      SETTING: Hirosaki University Hospital. PARTICIPANTS: Patients who underwent
      cardiovascular surgery without preoperative infection and end-stage kidney
      disease requiring dialysis. The patients also were subdivided into 2 groups with
      respect to the use of cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN
      RESULTS: Presepsin, PCT, and CRP were measured 4 times: before the induction of
      anesthesia (baseline), postoperative day (POD) 0, POD 1, and POD 2. Data are
      expressed as median (25th, 75th interquartiles). A total of 33 patients were
      examined: 22 patients with CPB and 11 without CPB. For the entire patient series,
      the presepsin concentrations on POD 0 (220 [166-445] pg/mL), POD 1 (328 [210-581]
      pg/mL), and POD 2 (310 [202-368] pg/mL) were increased significantly (p < 0.05)
      compared with baseline (176 [123-275] pg/mL). The PCT and CRP concentrations on
      POD 1 (0.57 [0.27-1.29] ng/mL and 5.4 [3.1-8.8] mg/dL) and POD 2 (0.64 [0.33
      1.43] ng/mL and 11.8 [4.4-17.0] mg/dL) also were increased significantly (p <
      0.05) compared with baseline (0.04 [0.03-0.06] ng/mL and 0.07 [0.03-0.22] mg/dL).
      However, the median concentrations of presepsin up to POD 2 were less than the
      reported cut-off value (600 pg/mL) to detect infections, whereas those of PCT
      were above the reported cut-off value (0.5 ng/mL). The increases in presepsin and
      PCT concentrations were independent of the use of CPB. CONCLUSIONS:
      Cardiovascular surgery significantly increased presepsin concentrations, earlier
      than PCT and CRP.

PMID- 28431810
TI  - In vivo ameliorative effect of cerium oxide nanoparticles in isoproterenol
      induced cardiac toxicity.
AB  - BACKGROUND: Cerium oxide nanoparticles have gained much more attention especially
      in the field of nanomedicine. This work represents cerium oxide nanoparticles as
      a new prophylactic model for heart failure progression. OBJECTIVE: To investigate
      the potential protective effect of cerium oxide nanoparticles on Isoproterenol
      (ISO)-induced cardiac toxicity in rats. METHODS: Cerium oxide nanoparticles (5+/
      1nm) were synthesized by reverse micelle method and characterized using High
      Resolution Transmission Electron Microscopy, X-Ray Diffraction and particle size
      analyzer. The experiments were performed on 96 male Wistar rats. The rats were
      randomly allocated into eight groups. Namely; two Negative and positive control
      groups, captopril administered group, Nano-ceria (low dose) group, Nano-ceria
      (high dose) group, Captopril- Isoproterenol group, Nano-ceria (low dose)
      Isoproterenol group and Nano-ceria (high dose)-Isoproterenol group. Cardio toxic
      rat model was induced by subcutaneous administration of Isoproterenol (ISO)
      (30mg/kg) for two consecutive days in adult male rats. Two doses (0.5 and
      5MUg/kg/week) of cerium oxide nanoparticles were applied for five weeks and
      50mg/kg/day of Captopril was used as a reference drug. Cardiac marker enzymes,
      Cortisol and Aldosterone hormones were assessed in serum. Oxidant-antioxidant
      parameters and histopathological examination in heart tissues were also
      determined. RESULTS: These dose of nano-ceria, showed a promising ameliorative
      and prophylactic effect against cardiac toxicity compared to Captopril reference
      drug. Serum cardiac markers were decreased by noticeable percentage, CK-MB (50%
      and 57%), LDH (47% and 57.7%), AST (38% and 36.5%) and ALT (33.5% and 30.6%) for
      both doses respectively, while increased tissues level of the antioxidant
      enzymes, catalase (48% - 26%) and superoxide dismutase (64%, 143%). CONCLUSION:
      These consistent biochemical and histopathological results suggest that, nano
      ceria could be used as effective antioxidant in prophylactic protocols for
      management of cardiac disorders associated with oxidative stress.

PMID- 28431811
TI  - Potential Consequences of Not Using Live Attenuated Influenza Vaccine.
AB  - INTRODUCTION: Decreased live attenuated influenza vaccine (LAIV) effectiveness in
      the U.S. prompted the Advisory Committee on Immunization Practices in August 2016
      to recommend against this vaccine's use. However, overall influenza uptake
      increases when LAIV is available and, unlike the U.S., LAIV has retained its
      effectiveness in other countries. These opposing countercurrents create a
      dilemma. METHODS: To examine the potential consequences of the decision to not
      recommend LAIV, which may result in decreased influenza vaccination coverage in
      the U.S. population, a Markov decision analysis model was used to examine
      influenza vaccination options in U.S. children aged 2-8 years. Data were compiled
      and analyzed in 2016. RESULTS: Using recently observed low LAIV effectiveness
      values, fewer influenza cases will occur if LAIV is not used compared with having
      LAIV as a vaccine option. However, having the option to use LAIV may be favored
      if LAIV effectiveness returns to prior levels or if the absence of vaccine choice
      substantially decreases overall vaccine uptake. CONCLUSIONS: Continued
      surveillance of LAIV effectiveness and influenza vaccine uptake is warranted,
      given their importance in influenza vaccination policy decisions.

PMID- 28431812
TI  - Potency of whole virus particle and split virion vaccines using dissolving
      microneedle against challenges of H1N1 and H5N1 influenza viruses in mice.
AB  - Transdermal vaccination using a microneedle (MN) confers enhanced immunity
      compared with subcutaneous (SC) vaccination. Here we developed a novel dissolving
      MN patch for the influenza vaccine. The potencies of split virion and whole virus
      particle (WVP) vaccines prepared from A/Puerto Rico/8/1934 (H1N1) and
      A/duck/Hokkaido/Vac-3/2007 (H5N1), respectively, were evaluated. MN vaccination
      induced higher neutralizing antibody responses than SC vaccination in mice.
      Moreover, MN vaccination with a lower dose of antigens conferred protective
      immunity against lethal challenges of influenza viruses than SC vaccination in
      mice. These results suggest that the WVP vaccines administered using MN are an
      effective combination for influenza vaccine to be further validated in humans.

PMID- 28431813
TI  - Evaluation of immune responses of stabilised SAT2 antigens of foot-and-mouth
      disease in cattle.
AB  - Foot-and-mouth disease (FMD) vaccines with improved stability and less reliant on
      a cold-chain are needed to improve the longevity of immune responses elicited in
      animals. This is especially so for serotypes O and SAT2 which are unstable in
      mildly acidic pH conditions or at elevated temperatures leading to dissociation
      of the capsid (146S particle) and loss of immunogenicity. Previously, stabilised
      SAT2 viruses were generated by reverse genetic approaches and assessed in vitro
      and in vivo with a guinea pig trial. Here we investigated the efficacy and
      comparative immunological responses of two thermostable and wild-type SAT2
      vaccines over 5months followed by challenge. We assessed humoral immune responses
      elicited in cattle in terms of total and neutralizing antibodies and IgG1/2
      isotyping; and cell-mediated responses of IFN-gamma as in vitro markers of
      protection. Whilst there were significant differences in total and neutralizing
      antibodies for the vSAT2-93H group compared to other vaccinated groups after the
      first vaccination, there were no significant differences after the second
      immunization. Following intra-dermolingual challenge all vaccinated groups were
      fully protected as determined by the absence of generalized lesions. These
      results provide proof that two vaccine doses, consisting of SAT2 antigen combined
      with ISA206B adjuvant, administered 4-6 weeks apart were able to protect animals
      up to 5months pv. Additionally, vSAT2-93Y had significantly higher levels of IFN
      gamma after challenge and had a lower clinical score indicative of better
      protection compared to other vaccinated groups and the importance of cell
      mediated responses and antigen stability in protection.

PMID- 28431814
TI  - Evaluation of storing hepatitis B vaccine outside the cold chain in the Solomon
      Islands: Identifying opportunities and barriers to implementation.
AB  - Monovalent Hepatitis B vaccine (HepB) is heat stable, making it suitable for
      storage outside cold chain (OCC) at 37 degrees C for 1month. We conducted an OCC
      project in the Solomon Islands to determine the feasibility of and barriers to
      national implementation and to evaluate impact on coverage. Healthcare workers at
      13 facilities maintained monovalent HepB birth dose (HepB-BD) OCC for up to
      28days over 7months. Vaccination data were recorded for children born during the
      project and those born during 7months before the project. Timely HepB-BD coverage
      among facility and home births increased from 30% to 68% and from 4% to 24%,
      respectively. Temperature excursions above 37 degrees C were rare, but vaccine
      wastage was high and shortages common. Storing HepB OCC can increase HepB-BD
      coverage in countries with insufficient cold chain capacity or numerous home
      births. High vaccine wastage and unreliable vaccine supply must be addressed for
      successful implementation.

PMID- 28431815
TI  - Efficacy and safety of high-dose influenza vaccine in elderly adults: A
      systematic review and meta-analysis.
AB  - INTRODUCTION: Older adults are prioritized for influenza vaccination but also
      have lowered antibody responses to the vaccine. Higher-doses of influenza antigen
      may increase immune response and thus be more effective. Our objectives were to
      compare the efficacy and safety of the high-dose influenza vaccine to the
      standard-dose influenza vaccine in the elderly (age>65). METHODS: Data sources:
      Randomized trials (RCTs) from Medline (Ovid), EMBASE (Ovid), Cochrane Library
      (Wiley), ClinicalTrials.gov, reference lists of relevant articles, and gray
      literature. STUDY SELECTION: Two reviewers independently identified RCTs
      comparing high-dose influenza vaccine (60MUg of hemagglutinin per strain) to
      standard-dose influenza vaccine (15MUg of hemagglutinin per strain) in adults
      over the age of 65years. DATA EXTRACTION: Two reviewers independently extracted
      trial-level data including population characteristics, interventions, outcomes,
      and funding sources. Risk of bias was assessed using the Cochrane Risk of Bias
      tool. RESULTS: We included seven eligible trials; all were categorized as having
      a low (n=3) or unclear (n=4) risk of bias. Patients receiving the high-dose
      vaccine had significantly less risk of developing laboratory-confirmed influenza
      infections (Relative Risk 0.76, 95%CI 0.65 to 0.90; I2 0%, 2 trials, 41,141
      patients). Post-vaccination geometric mean titres and seroprotection rates were
      also higher in high-dose vaccine recipients. There were no protocol-defined
      serious adverse events in the included trials in either group. CONCLUSIONS: In
      elderly adults, the high-dose influenza vaccine was well-tolerated, more
      immunogenic, and more efficacious in preventing influenza infections than the
      standard-dose vaccine. Further pragmatic trials are needed to determine if the
      higher efficacy translates into higher vaccine effectiveness in adults over the
      age of 65.

PMID- 28431816
TI  - Role of controlled human malaria infection (CHMI) in malaria vaccine development:
      A U.S. food & drug administration (FDA) perspective.

PMID- 28431817
TI  - Pneumococcal carriage among children after four years of routine 10-valent
      pneumococcal conjugate vaccine use in Brazil: The emergence of multidrug
      resistant serotype 6C.
AB  - BACKGROUND: In 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was
      introduced free of charge in Brazil as part of the public immunization program.
      Here we investigated the carriage prevalence, colonization risk factors, capsular
      types, and antimicrobial resistance among pneumococcal isolates obtained from
      children in Brazil four years after routine PCV10 use. METHODS: Between September
      and December 2014, we conducted a cross-sectional study among children<6years old
      who attended one public and two private clinics in Niteroi, RJ, Brazil to
      evaluate pneumococcal nasopharyngeal carriage. Antimicrobial susceptibility and
      capsular types were determined for all isolates. RESULTS: Of 522 children, 118
      (22.6%) were pneumococcal carriers. Being>=2years old, attending childcare
      center, presenting with any symptoms, having acute or chronic respiratory
      disease, and residing in a slum were associated with pneumococcal carriage. The
      most prevalent capsular types were 6C (14.5%), 15B/C (11.5%), 11A/D (9.2%), and
      6A (7.6%). PCV10 serotypes represented 2.5%. All isolates were susceptible to
      levofloxacin, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci
      (PNSP) comprised 39%, with penicillin and ceftriaxone MICs ranging from 0.12
      8.0MUg/ml and 0.012-1.0MUg/ml, respectively. The 33 (28%) erythromycin-resistant
      isolates (MICs of 1.5 to >256MUg/ml) displayed the cMLSB (72.7%) or M (27.3%)
      phenotypes, harboring the erm(B) and/or mef(A/E) genes. High non-susceptibility
      rates (>20%) to clindamycin, erythromycin, penicillin, and tetracycline were
      largely explained by the prevalence of multidrug resistant (MDR) serotype 6C
      isolates. CONCLUSIONS: Effects of universal childhood PCV10 use on carriage were
      evident, with the near elimination of PCV10 serotypes. The emergence of MDR
      serotype 6C isolates, however, is a concern. Ongoing surveillance to monitor
      serotype 6C increase in invasive diseases is warranted.

PMID- 28431818
TI  - The comparison of point-of-care ultrasonography and radiography in the diagnosis
      of tibia and fibula fractures.
AB  - OBJECTIVE: We aimed to compare the efficacy of Point-of-care ultrasonography
      (POCUS) with radiography in the diagnosis of tibia fracture (TF) and fibula
      fracture (FF), and determation of fracture characteristics. METHODS: Patients
      aged 5-55 years who were admitted to ED due to low-energy, simple extremity
      trauma, who had a suspected TF and FF on physical examination were included in
      this prospective study. One physician performed POCUS examination. Other
      physician evaluated the radiography images. The obtained results were compared.
      RESULTS: A total of 62 patients were included in the study. TF was detected in 21
      patients by radiography and in 24 patients by POCUS. FF was detected in 24
      patients by radiography and in 25 patients by POCUS. Ten of the patients had both
      TF and FF. Compared with radiography, sensitivity, specificity, PPV and NPV of
      POCUS in the detection of TF were 100%, 93%, 88% and 100% (95% CI, 91-100%),
      respectively. Compared with direct X-ray imaging, sensitivity, specificity, PPV
      and NPV of POCUS in the detection of FF were 100%, 97%, 96% and 100% (95% CI, 96
      100%), respectively. We determined that POCUS is also successful in detection of
      fracture features such as angulation, step-off, extension into the joint space
      that can determine the treatment decision. CONCLUSION: This study demonstrated
      that POCUS was found to be as successful as direct X-ray imaging in the diagnosis
      of TF and FF.

PMID- 28431819
TI  - Denosumab in bone marrow oedema syndrome.

PMID- 28431820
TI  - Commentary on "Near Infrared Spectroscopy as a Predictor for Shunt Requirement
      During Carotid Endarterectomy".

PMID- 28431821
TI  - Near Infrared Spectroscopy as a Predictor for Shunt Requirement During Carotid
      Endarterectomy.
AB  - OBJECTIVE/BACKGROUND: Near infrared spectroscopy (NIRS) continuously monitors
      regional cerebral oxygenation (rSO2) in the frontal lobes. This method may be
      used in patients during carotid endarterectomy to indicate the need for shunting.
      The aim of the study was to evaluate the value of NIRS in determining the need
      for selective shunting during CEA. A secondary aim was to compare NIRS with stump
      pressure. METHODS: Between January 2013 and October 2016, 185 patients from two
      vascular units, undergoing CEA under local anaesthesia were prospectively
      included. All patients gave informed consent to participate; there were no
      exclusion criteria. A Foresight(r) oximeter was used for rSO2 measurement, which
      was compared with stump pressure. Receiver operating characteristic curve
      analysis was used to identify optimal cutoff points, and sensitivity,
      specificity, and positive and negative predictive values were calculated.
      RESULTS: Twenty patients (10.8%) developed neurological symptoms during clamping.
      Mean stump pressure was lower in the group that developed neurological symptoms
      than in the group who did not (34 +/- 19 mmHg vs. 55 +/- 17 mmHg [p < . 01]).
      Corresponding NIRS results for the decrease in rSO2 on the ipsilateral side was
      15 +/- 7% versus 4 +/- 6% (p < .01). Using stump pressure <=50 mmHg as cutoff
      value for predicting symptoms, the sensitivity was 85% (95% confidence interval
      [CI] 64-95) and specificity 54% (95% CI 46-61). With a relative decrease in NIRS
      saturation (DeltarSO2) of 9%, sensitivity was 95% (95% CI 76-99), and specificity
      81% (95% CI 74-86) to predict ischaemic symptoms during carotid clamping.
      Neurological deterioration during carotid clamping was detected in one patient
      with a relative decrease in rSO2 of <9% compared with three patients with a stump
      pressure >50 mmHg. CONCLUSION: NIRS allows continuous non-invasive monitoring of
      cerebral oxygenation during CEA, with high sensitivity and acceptable specificity
      in predicting cerebral ischaemia and the need for shunting, which makes it an
      attractive alternative to stump pressure.

PMID- 28431822
TI  - Detecting bursts in the EEG of very and extremely premature infants using a multi
      feature approach.
AB  - AIM: To develop a method that segments preterm EEG into bursts and inter-bursts
      by extracting and combining multiple EEG features. METHODS: Two EEG experts
      annotated bursts in individual EEG channels for 36 preterm infants with
      gestational age < 30 weeks. The feature set included spectral, amplitude, and
      frequency-weighted energy features. Using a consensus annotation, feature
      selection removed redundant features and a support vector machine combined
      features. Area under the receiver operator characteristic (AUC) and Cohen's kappa
      (kappa) evaluated performance within a cross-validation procedure. RESULTS: The
      proposed channel-independent method improves AUC by 4-5% over existing methods (p
      < 0.001, n=36), with median (95% confidence interval) AUC of 0.989 (0.973-0.997)
      and sensitivity-specificity of 95.8-94.4%. Agreement rates between the detector
      and experts' annotations, kappa=0.72 (0.36-0.83) and kappa=0.65 (0.32-0.81), are
      comparable to inter-rater agreement, kappa=0.60 (0.21-0.74). CONCLUSIONS:
      Automating the visual identification of bursts in preterm EEG is achievable with
      a high level of accuracy. Multiple features, combined using a data-driven
      approach, improves on existing single-feature methods.

PMID- 28431823
TI  - Sleepiness and activity in heart failure patients with reduced ejection fraction
      and central sleep-disordered breathing.
AB  - OBJECTIVE: Patients with heart failure (HF) and sleep disordered breathing (SDB)
      are typically not sleepy, unlike patients without heart failure. Previous work in
      HF patients with obstructive SDB suggested that sleepiness was associated with a
      reduction in daytime activity. The consequences of predominately central SDB on
      sleepiness in HF are less well understood. The aim of this study was to test the
      hypothesis that subjective sleepiness is associated with reduced daytime activity
      in HF patients with central SDB, compared to those without SDB. METHODS: The
      Epworth Sleepiness Scale (ESS), nocturnal polysomnography, and 14 days of wrist
      watch actigraphy were used to assess subjective daytime sleepiness, nocturnal
      sleep and breathing, and 24-h activity levels, respectively. RESULTS: A total of
      54 patients with HF were studied, nine had obstructive SDB and were removed from
      further analysis. Of the patients, 23 had HF with predominantly central SDB (HF
      CSA; apnea-hypopnea index (AHI) median 20.6 (IQR 12.9-40.2)/h), and 22 had noSDB
      (HF-noSDB; AHI 3.7 (2.5-5.9)/h). The median patient age was 68 years (range 59-73
      years). There were no significant differences either in ESS score (HF-CSA; 8 [4
      10] vs. HF-noSDB; 8 (6-12); p = 0.49) or in duration of daytime activity (HF-CSA
      14.5 (14.1-15.2) and HF-noSDB 15.1 (14.4-15.3) hours; p = 0.10) between the
      groups. CONCLUSION: HF patients with predominately central SDB are not
      subjectively sleepy compared to those without SDB, despite reduced sleep quality.
      We speculate that the lack of sleepiness (based on ESS score) may be due to
      increased sympathetic nerve activity, although further studies are needed due to
      the small number (n = 5) of sleepy HF-CSA patients. Daytime activity was not
      different between HF-noSDB and HF-CSA patients.

PMID- 28431824
TI  - An observational study of the quality of ECGs recorded by inexperienced staff in
      a resource-poor African hospital using a reusable ECG belt linked to an internet
      ECG device.

PMID- 28431825
TI  - Single Subcortical Infarct: Pathomechanism Assessed by Thin-Section Computed
      Tomography Perfusion.
AB  - INTRODUCTION: The pathomechanism of a single subcortical infarct (SSI) may be
      better determined by assessing the perfusion status between parent artery and
      ischemic lesion. We aimed to compare the classifications into branch atheromatous
      disease (BAD) versus non-BAD based on diffusion-weighted imaging (DWI) or
      computed tomography perfusion (CTP), and to test whether a CTP-based
      classification improves the predicting power for progression in SSI (PSSI)
      compared to that by DWI. METHODS: We enrolled 109 consecutive patients with SSI
      examined by whole-supratentorial brain CTP and follow-up DWI. Time-to-drain (TTD)
      maps were calculated from 1-mm dynamic CTP data. BAD was assumed when either the
      ischemic lesion extended to the basal surface of the parent artery on axial DWI
      or the hypoperfused area (TTD >= 5 seconds) was <5 mm apart from the
      cerebrospinal fluid perforators interface on both coronal and sagittal CTPs. We
      tested the relationship between DWI and CTP for determining BAD, and compared
      demographics, imaging, and the frequency of PSSI between the BAD and non-BAD
      based on CTP. Multivariable regression analysis was performed to determine
      predicting factors for PSSI. RESULTS: On DWI, 66 of 109 patients (60.6%) were
      classified as BAD; on CTP, 32 patients were classified as BAD (29.4%), showing
      significant difference (P = .047). PSSI was significantly different between BAD
      versus non-BAD by CTP (40.6% versus 11.7%, P = .002), but not different by DWI
      (21.2% versus 18.6%, P = .930). BAD-type perfusion was the only independent
      predictor for PSSI (OR, 5.209; 95% CI, 1.745-15.555; P = .003). CONCLUSION: The
      classifications of SSI with and without BAD by CTP and DWI are significantly
      different. CTP may help to predict PSSI.

PMID- 28431827
TI  - First Described Envenomation by Centruroides pococki Scorpion in the French
      Caribbean Island Guadeloupe.

PMID- 28431828
TI  - Clinical use of monopronucleated zygotes following blastocyst culture and
      preimplantation genetic screening, including verification of biparental
      chromosome inheritance.
AB  - In assisted reproduction, embryos derived from monopronucleated (1PN) zygotes are
      considered abnormal and unsuitable for clinical use. Outcomes of 1PN-derived
      embryos designated for preimplantation genetic screening (PGS) were analysed.
      These embryos, especially from intracytoplasmic sperm injection (ICSI), were
      found to have a low developmental potential; 1PN and 2PN day 5 blastocyst
      development for IVF was 14.8% versus 36.4% (P < 0.0001), and for ICSI, 6.6%
      versus 34.0% (P < 0.0001), respectively. With the use of comparative genomic
      hybridization or next-generation sequencing, PGS was successfully carried out for
      74 IVF and 32 ICSI 1PN-derived blastocysts, revealing adjusted abnormality rates
      of 39.7% and 40.6%, respectively. Additionally, 24 female 1PN-derived blastocysts
      underwent testing for biparental inheritance, with one ICSI-derived embryo
      demonstrating paternal only contribution, thus presenting a risk for complete
      hydatidiform molar pregnancy. Single embryo transfer of 20 IVF and six ICSI 1PN
      derived blastocysts with no detectable abnormalities resulted in nine clinical
      pregnancies. Six have been delivered and three are ongoing, with no anomalies
      reported to date. The limitation of this study is that pronuclear status was
      determined through one static observation. The results suggest that 1PN-derived
      embryos, in which euploidy and biparental inheritance have been established, can
      provide a source of clinically useful embryos.

PMID- 28431829
TI  - Utility of the new Movement Disorder Society clinical diagnostic criteria for
      Parkinson's disease applied retrospectively in a large cohort study of recent
      onset cases.
AB  - OBJECTIVE: To examine the utility of the new Movement Disorder Society (MDS)
      diagnostic criteria in a large cohort of Parkinson's disease (PD) patients.
      METHODS: Recently diagnosed (<3.5 years) PD cases fulfilling United Kingdom (UK)
      brain bank criteria in Tracking Parkinson's, a UK multicenter prospective natural
      history study were assessed by retrospective application of the MDS criteria.
      RESULTS: In 2000 cases, 1835 (91.7%) met MDS criteria for PD, either clinically
      established (n = 1261, 63.1%) or clinically probable (n = 574, 28.7%), leaving
      165 (8.3%) not fulfilling criteria. Clinically established cases were
      significantly more likely to have limb rest tremor (89.3%), a good l-dopa
      response (79.5%), and olfactory loss (71.1%), than clinically probable cases
      (60.6%, 44.4%, and 34.5% respectively), but differences between probable PD and
      'not PD' cases were less evident. In cases not fulfilling criteria, the mean MDS
      UPDRS3 score (25.1, SD 13.2) was significantly higher than in probable PD (22.3,
      SD 12.7, p = 0.016) but not established PD (22.9, SD 12.0, p = 0.066). The l-dopa
      equivalent daily dose of 341 mg (SD 261) in non-PD cases was significantly higher
      than in probable PD (250 mg, SD 214, p < 0.001) and established PD (308 mg, SD
      199, p = 0.025). After 30 months' follow-up, 89.5% of clinically established
      cases at baseline remained as PD (established/probable), and 86.9% of those
      categorized as clinically probable at baseline remained as PD
      (established/probable). Cases not fulfilling PD criteria had more severe
      parkinsonism, in particular relating to postural instability, gait problems, and
      cognitive impairment. CONCLUSION: Over 90% of cases clinically diagnosed as early
      PD fulfilled the MDS criteria for PD. Those not fulfilling criteria may have an
      atypical parkinsonian disorder or secondary parkinsonism that is not correctly
      identified by the UK Brain Bank criteria, but possibly by the new criteria.

PMID- 28431830
TI  - [Post-orgasmic illness syndrome].

PMID- 28431831
TI  - Speaking and Nonspeaking Voice Professionals: Who Has the Better Voice?
AB  - INTRODUCTION: Voice professionals can be classified into two major subgroups: the
      primarily speaking and the primarily nonspeaking voice professionals. Nonspeaking
      voice professionals mainly include singers, whereas speaking voice professionals
      include the rest of the voice professionals. Although both of these groups have
      high vocal demands, it is currently unknown whether both groups show similar
      voice changes after their daily voice use. Comparison of these two subgroups of
      voice professionals has never been done before. AIM: This study aimed to compare
      the speaking voice of speaking and nonspeaking voice professionals with no
      obvious vocal fold pathology or voice-related complaints on the day of
      assessment. METHODOLOGY: After obtaining relevant voice-related history, voice
      analysis and videostroboscopy were performed in 50 speaking and 50 nonspeaking
      voice professionals. RESULTS: Speaking voice professionals showed significantly
      higher incidence of voice-related complaints as compared with nonspeaking voice
      professionals. Voice analysis revealed that most acoustic parameters including
      fundamental frequency, jitter percent, and harmonic-to-noise ratio were
      significantly higher in speaking voice professionals, whereas videostroboscopy
      did not show any significant difference between the two groups. CONCLUSION: This
      is the first study of its kind to analyze the effect of daily voice use in the
      two subgroups of voice professionals with no obvious vocal fold pathology. We
      conclude that voice professionals should not be considered as a homogeneous
      group. The detrimental effects of excessive voice use were observed to occur more
      significantly in speaking voice professionals than in nonspeaking voice
      professionals.

PMID- 28431832
TI  - Unravelling the mysteries of sudden unexpected death in epilepsy.
AB  - INTRODUCTION: Sudden unexpected death in epilepsy (SUDEP) is the most frequent
      cause of premature death in epileptic patients. Most SUDEP events occur at night
      and frequently go unnoticed; the exact pathophysiological mechanisms of this
      phenomenon therefore remain undetermined. Nevertheless, most cases of SUDEP are
      attributed to an infrequent yet extremely severe complication of epileptic
      seizures. DEVELOPMENT: We conducted a systematic literature search on PubMed. Our
      review article summarises scientific evidence on the classification,
      pathophysiological mechanisms, risk factors, biomarkers, and prevention of SUDEP.
      Likewise, we propose new lines of research and critically analyse findings that
      are relevant to clinical practice. CONCLUSIONS: Current knowledge suggests that
      SUDEP is a heterogeneous phenomenon caused by multiple factors. In most cases,
      however, SUDEP is thought to be due to postictal cardiorespiratory failure
      triggered by generalised tonic-clonic seizures and ultimately leading to cardiac
      arrest. The underlying pathophysiological mechanism involves multiple factors,
      ranging from genetic predisposition to environmental factors. Risk of SUDEP is
      higher in young adults with uncontrolled generalised tonic-clonic seizures.
      However, patients apparently at lower risk may also experience SUDEP. Current
      research focuses on identifying genetic and neuroimaging biomarkers that may help
      determine which patients are at high risk for SUDEP. Antiepileptic treatment is
      the only preventive measure proven effective to date. Night-time monitoring
      together with early resuscitation may reduce the risk of SUDEP.

PMID- 28431833
TI  - Headache after carotid artery stenting.
AB  - INTRODUCTION AND OBJECTIVES: Headache after carotid artery stenting is a headache
      with onset during the procedure or in the first few hours after it, and where
      there is no evidence to suggest a complication of that procedure. The purpose of
      this study is to describe the main features of these headaches based on our
      clinical experience. PATIENTS AND METHODS: Observational prospective study of a
      sample of patients undergoing carotid artery stenting at Hospital Clinico
      Universitario Lozano Blesa, in Zaragoza, Spain. We recorded sociodemographic
      characteristics, cardiovascular risk factors, carotid artery disease, and history
      of primary headache; data were gathered using structured interviews completed
      before and 24hours after the procedure. RESULTS: We included 56 patients (mean
      age 67+/-9.52 years); 84% were men. Twelve patients (21.4%) experienced headache,
      83.3% of whom were men; mean age was 60.58+/-9.31 years. Headache appeared within
      the first 6hours in 7 patients (58.4%) and during the procedure in 4 (33.3%).
      Pain lasted less than 10minutes in 4 patients (33.3%) and between 10 and
      120minutes in 5 (41.7%). Headache affected the frontotemporal area in 7 patients
      (58.3%); 7 patients (58.3%) described pain as unilateral. It was oppressive in 8
      patients (66.7%) and of moderate intensity in 6 (50%). Nine patients (75%)
      required no analgesics. We found no statistically significant associations with
      any of the variables except for age (P=.007; t test). CONCLUSIONS: In our sample,
      headache after carotid artery stenting was mild to moderate in intensity,
      unilateral, oppressive, and short-lasting. Further studies are necessary to gain
      a deeper knowledge of its characteristics and associated risk factors.

PMID- 28431834
TI  - Pollakiuria as a complex motor tic in a patient with Tourette syndrome.

PMID- 28431835
TI  - Variability in the use of neuroimaging techniques for diagnosis and follow-up of
      stroke patients.
AB  - INTRODUCTION AND OBJECTIVE: Imaging diagnosis is essential for treatment planning
      in stroke patients. However, use of these techniques varies due to uncertainty
      about their effectiveness. Our purpose was to describe the use of CT and MRI in
      stroke and transient ischaemic attack (TIA) over 5years in hospitals belonging to
      the Canary Islands Health Service and analyse interhospital variability based on
      routinely collected administrative data. PATIENTS AND METHOD: We gathered the
      minimum basic dataset (MBDS) from patients diagnosed with stroke or TIA between
      2005 and 2010 in 4hospitals. Patients' age, sex, procedures, secondary diagnoses,
      and duration of hospital stay were also recorded. We conducted a descriptive
      analysis of patient characteristics and a bivariate analysis using the t test and
      the chi square test to detect differences between patients assessed and not
      assessed with MRI. Logistic regression was used to analyse unequal access to MRI.
      RESULTS AND CONCLUSIONS: Our study included 10,487 patients (8,571 with stroke
      and 1,916 with TIA). The percentage of stroke patients undergoing a CT scan
      increased from 89.47% in 2005 to 91.50% in 2010. In these patients, use of MRI
      also increased from 25.41% in 2005 to 36.02% in 2010. Among patients with TIA,
      use of CT increased from 84.64% to 88.04% and MRI from 32.53% to 39.13%.
      According to our results, female sex, younger age, and presence of comorbidities
      increase the likelihood of undergoing MRI.

PMID- 28431836
TI  - Spinal promyelocytic sarcoma as the initial manifestation of acute promyelocytic
      leukaemia.

PMID- 28431837
TI  - Recurrent lacrimal neuralgia secondary to ophthalmological procedures.

PMID- 28431838
TI  - Global developmental delay and postnatal microcephaly: Bainbridge-Ropers syndrome
      with a new mutation in ASXL3.

PMID- 28431839
TI  - Day of the week for the assessment of orientation in time.

PMID- 28431840
TI  - Novel probable pathological variant c.1249A>C in exon 7 of the GAA gene
      associated with Pompe disease in adults.

PMID- 28431841
TI  - Cognitive profile and disorders affecting higher brain functions in paediatric
      patients with neurofibromatosis type 1.
AB  - INTRODUCTION: Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome
      often associated with specific cognitive deficits that are rarely monitored
      during follow-up of these patients. OBJECTIVE: The purpose of our study is two
      fold. First, we aimed to describe the cognitive profile of patients with NF1 and
      detect disorders in higher brain functions associated with the disease. Second,
      we identified the reasons for consultation associated with school performance in
      these patients. METHODS: We conducted a descriptive cross-sectional study of 24
      paediatric patients (ages 5 to 16) with NF1 who underwent neuropsychological
      assessment. RESULTS: The most frequent reasons for consultation were attention
      deficits (58.33%), learning disorders (25%), poor motor coordination (25%), and
      language impairment (0.8%). Although 96% of the patients displayed impairments in
      at least one of the assessed areas, only 83.34% of the parents had reported such
      impairments. Attention-deficit/hyperactivity disorder was present in 58.33% of
      the patients, whereas 33.33% had nonverbal learning disabilities, 20.83% had
      expressive language disorder, 8.33% had borderline intellectual functioning,
      4.16% had mental retardation, and only 4.16% showed no cognitive impairment.
      CONCLUSION: Higher brain functions are frequently impaired in paediatric patients
      with NF1. Although many parents report such disorders, they can go undetected in
      some cases. Neuropsychological assessment is recommended for all paediatric
      patients with NF1 to detect cognitive impairment and provide early, effective
      rehabilitation treatment.

PMID- 28431842
TI  - Significance of intraoperative findings in revision tympanomastoidectomy.
AB  - PURPOSE: The study was designed to assess correlations between intraoperative
      findings in revision tympanomastoidectomy as predictors of cholesteatoma
      recurrence. MATERIALS AND METHODS: A retrospective single-institution cohort of
      101 patients who underwent surgical treatment for recurrent chronic otitis media
      in a tertiary referral otology centre. RESULTS: Out of 101 patients, 65 had canal
      wall up and 36 canal wall down revision surgery. There were 35 cholesteatoma
      recurrences. Sites most commonly associated with recurrent disease were residual
      facial ridge cells in 46 (45.5%), ossicular chain sites in 46 (45.5%) patients,
      posterior external auditory canal wall erosions in 38 (37.6%) patients and
      mastoid apex recurrence in 35 (34.7%) patients. Ossicular and posterior external
      auditory canal wall erosion and incomplete removal of mastoid apex cells
      correlate well with cholesteatoma recurrence accompanied by canal wall up surgery
      (p=0.009). Residual mastoid apex cells, posterior external auditory canal wall
      erosion and presence of residual facial ridge cells were identified as the
      strongest positive predictors of cholesteatoma recurrence, identifying high risk
      patients associated with canal wall down procedures (p=0.0036). CONCLUSIONS:
      Correlations between intraoperative findings and cholesteatoma recurrence could
      improve preoperative and intraoperative planning and reduce the rates of
      postoperative failures1 due to mismanagement of high risk areas.

PMID- 28431843
TI  - On the complex interaction between mathematics and the sciences of living
      systems: Comment on "Move me, astonish me...delight my eyes and brain: The Vienna
      Integrated Model of top-down and bottom-up processes in Art Perception (VIMAP)
      and corresponding affective, evaluative, and neurophysiological correlates" by
      Matthew Pelowski et al.

PMID- 28431844
TI  - Health care-associated infections studies project: An American Journal of
      Infection Control and National Healthcare Safety Network data quality
      collaboration.
AB  - This case study is part of a series centered on the Centers for Disease Control
      and Prevention's National Healthcare Safety Network's (NHSN) health care
      associated infection (HAI) surveillance definitions. The intent of the case study
      series is to foster standardized application of the NHSN's HAI surveillance
      definitions among infection preventionists and accurate determination of HAI
      events. This specific case study focuses on the definitions found within the
      surgical site infection (SSI) protocol. It aims to reflect the real life and
      complex patient scenario surrounding a bloodstream infection that is secondary to
      an SSI and the application of the Present at the Time of Surgery event detail. An
      online survey link is provided where participants may confidentially answer
      questions related to the case study and receive immediate feedback in the form of
      correct answers and explanations and rationales. Details of the case study,
      answers, and explanations have been reviewed and approved by NHSN staff. We hope
      that participants take advantage of this educational offering and thereby gain a
      greater understanding of the NHSN's HAI surveillance definitions.

PMID- 28431845
TI  - Infection prevention and control and the refugee population: Experiences from the
      University of Louisville Global Health Center.
AB  - BACKGROUND: During 2016, approximately 140,000 individuals entered the United
      States as part of the federal government refugee resettlement program and
      established themselves in communities in virtually every state. No national
      database regarding refugee health currently exists; therefore, little is known
      about existing infectious diseases, conditions, and cultural practices that
      impact successful acculturation. The objective of this report is to identify what
      is currently known about refugees and circumstances important to infection
      prevention and control with respect to their roles as new community members,
      employees, and consumers of health care. METHODS: Using data from the University
      of Louisville Global Health Center's Newly Arriving Refugee Surveillance System,
      health issues affecting refugees from the perspective of a community member, an
      employee, and a patient were explored. RESULTS: Lack of immunity to vaccine
      preventable diseases is the most widespread issue impacting almost every adult,
      adolescent, and child refugee resettled in Kentucky. Health issues of concern
      from an infection prevention and control perspective include latent tuberculosis
      infection, HIV, hepatitis B, hepatitis C, syphilis, and parasites. Other health
      conditions that may also be important include anemia, obesity, oral health,
      diabetes, and cardiovascular disease. CONCLUSIONS: Refugee resettlement provides
      motivation for collaborative work among those responsible for infection
      prevention and control in all settings, their public health partners, and those
      responsible for and interested in community workforce concerns.

PMID- 28431846
TI  - Implementation of daily chlorhexidine bathing to reduce colonization by multidrug
      resistant organisms in a critical care unit.
AB  - BACKGROUND: Colonized patients are a reservoir for transmission of multidrug
      resistant organisms (MDROs). Not many studies have examined the effectiveness of
      daily chlorhexidine gluconate (CHG) bathing under routine care conditions. We
      present a descriptive analysis of the trends of MDRO colonization following
      implementation of daily CHG bathing under routine clinical conditions in an
      intensive care unit (ICU). METHODS: From May 2010-January 2011, we screened
      patients admitted to a 24-bed ICU for and methicillin-resistant Staphylococcus
      aureus (MRSA), vancomycin-resistant enterococci (VRE), and fluoroquinolone
      resistant gram-negative bacilli (FQRGNB). We calculated and plotted monthly
      incidence and prevalence of colonization of these MDROs. RESULTS: Prevalence
      decreased in the immediate aftermath of daily CHG bathing implementation and
      generally remained at that level throughout the observation period. We observed
      low rates of incidence of MDRO colonization with VRE>FQRGNB>MRSA. Monthly
      prevalence of colonization and incidence for the composite of MRSA, VRE, and/or
      FQRGNB was 1.9%-27.9% and 0-1.1/100 patient-days, respectively. CONCLUSIONS:
      Following the implementation of daily CHG bathing, the incidence of MDROs
      remained low and constant over time, whereas the prevalence decreased immediately
      after the implementation.

PMID- 28431847
TI  - Guideline compliance and clinical outcomes among patients with Staphylococcus
      aureus bacteremia with infectious diseases consultation in addition to
      antimicrobial stewardship-directed review.
AB  - OBJECTIVE: Previous studies have shown infectious diseases consultation (IDC) for
      Staphylococcus aureus bacteremia (SAB) improves management and outcomes. The
      influence of IDC on outcomes for SAB in addition to an antimicrobial stewardship
      program (ASP) review for adult inpatients with SAB has not been evaluated. The
      purpose of this study was to investigate the effect of IDC on SAB management with
      concomitant ASP review and resulting outcomes. METHODS: Adult inpatients with SAB
      admitted December 2012-October 2014 were included. The primary end point compared
      adherence to Infectious Disease Society of America guideline recommendations
      between patients receiving an IDC versus those not receiving an IDC. We also
      evaluated adherence to the individual components of the primary end point and
      clinical outcomes, including time to microbiologic clearance, recurrence of
      bacteremia, mortality, and length of stay. RESULTS: This study included 154
      patients (115 IDC and 39 non-IDC). Guideline adherence was significantly greater
      in the IDC group 78% versus 46% in the non-IDC group (P < .001). Significantly
      more patients in the IDC group had echocardiography (91% vs 67%; P < .001) and
      follow-up blood cultures (92% vs 64%; P > .001). Mortality was also greater in
      the non-IDC group (23%) versus 5% for the IDC group (P = .001). CONCLUSIONS:
      Patients with SAB receiving an IDC were more likely to receive guideline
      congruent management and had significantly reduced mortality. No improvements in
      antibiotic choice or dosing were observed, likely a result of ASP review.

PMID- 28431848
TI  - Epidemiology of device-associated infections in an intensive care unit of a
      teaching hospital in Nepal: A prospective surveillance study from a developing
      country.
AB  - BACKGROUND: Device-associated health care-acquired infections (DA-HAIs) in
      intensive care unit patients are a major cause of morbidity, mortality, and
      increased health care costs. METHODS: A prospective, structured
      clinicomicrobiological surveillance was carried out for 3 common DA-HAIs:
      ventilator-associated pneumonia (VAP), central line-associated bloodstream
      infection (CLABSI), and catheter-associated urinary tract infection (CAUTI)
      present in the patients of an intensive care unit of a teaching hospital in
      Nepal. DA-HAIs were identified using the Centers for Disease Control and
      Prevention definitions, and their rates were expressed as number of DA-HAIs per
      1,000 device-days. RESULTS: Overall incidence rate of DA-HAIs was 27.3 per 1,000
      patient-days occurring in 37.1% of patients. The device utilization ratio for
      mechanical ventilation, central line catheter, and urinary catheter was 0.83,
      0.63, and 0.78, respectively. The rates of VAP, CLABSI, and CAUTI were 21.40,
      8.64, and 5.11 per 1,000 device-days, respectively. Acinetobacter spp (32.7%),
      Klebsiella spp (23.6%), Burkholderia cepacia complex (12.7%), and Escherichia
      coli (10.9%) were the common bacterial pathogens. Most of the bacterial isolates
      associated with DA-HAIs were found to be multidrug-resistant. CONCLUSIONS:
      Incidence of DA-HAIs in the study intensive care unit was high compared with that
      of developed countries. Formulation and implementation of standard infection
      control protocols, active surveillance of DA-HAIs, and antimicrobial stewardship
      are urgently needed in our country.

PMID- 28431849
TI  - Prospective cluster controlled crossover trial to compare the impact of an
      improved hydrogen peroxide disinfectant and a quaternary ammonium-based
      disinfectant on surface contamination and health care outcomes.
AB  - BACKGROUND: Quaternary ammonium-based (Quat) disinfectants are widely used, but
      they have disadvantages. METHODS: This was a 12-month prospective cluster
      controlled crossover trial. On 4 wards, housekeepers performed daily cleaning
      using a disinfectant containing either 0.5% improved hydrogen peroxide (IHP) or
      Quat. Each month, 5-8 high-touch surfaces in several patient rooms on each ward
      were tagged with a fluorescent marker and cultured before and after cleaning.
      Hand hygiene compliance rates and antimicrobial usage on study wards were
      obtained from hospital records. Outcomes included aerobic colony counts (ACCs),
      percent of wiped surfaces yielding no growth after cleaning, and a composite
      outcome of incidence densities of nosocomial acquisition and infection caused by
      vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus,
      and Clostridium difficile infection. Statistical analysis was performed using
      chi2 test, Fisher exact test, Welch test, and logistic regression methods.
      RESULTS: Mean ACCs per surface after cleaning were significantly lower with IHP
      (14.0) than with Quat (22.2) (P = .003). The proportion of surfaces yielding no
      growth after cleaning was significantly greater with IHP (240/500; 48%) than with
      Quat (182/517; 35.2%) (P < .0001). Composite incidence density of nosocomial
      colonization or infection with IHP (8.0) was lower than with Quat (10.3)
      (incidence rate ratio, 0.77; P = .068; 95% confidence interval, 0.579-1.029).
      CONCLUSIONS: Compared with a Quat disinfectant, the IHP disinfectant
      significantly reduced surface contamination and reduced a composite colonization
      or infection outcome.

PMID- 28431850
TI  - Klebsiella pneumoniae carbapenemase-producing Serratia marcescens outbreak in a
      university hospital.

PMID- 28431851
TI  - Ultraviolet-C light as a means of disinfecting anesthesia workstations.
AB  - BACKGROUND: Anesthesia workstations (AWs) are a reservoir for pathogenic
      organisms potentially associated with surgical site infections. This study
      examined the effectiveness of the Tru-D SmartUVC device (Tru-D LLC, Nashville,
      TN) on bioburden reduction (BR) on AWs. METHODS: Strips of tissue inoculated with
      a known concentration of either Staphylococcus aureus, Enterococcus faecalis, or
      Acinetobacter sp were placed on 22 high-touch surfaces of an AW. Half of the AW
      surfaces received direct ultraviolet (UV) light exposure and half received
      indirect exposure. Two inoculated strips, in sterile tubes outside of the room,
      represented the control. Trials were conducted on AWs in an operating room and a
      small room. Strips were placed in a saline solution, vortexed, and plated on
      blood agar to assess BR by the number of colony forming units. RESULTS: All
      experimental trials, compared with controls, exhibited a BR >99%. There was a
      significantly greater reduction of E faecalis colony forming units in the
      operating room AW under direct exposure (P = .019) compared with indirect
      exposure. There was no significant difference in reduction when comparing AWs
      between rooms. CONCLUSION: Regardless of room size and exposure type, automated
      UV-C treatment greatly influences BR on AW high-touch surfaces. Hospitals
      instituting an automated UV-C system as an infection prevention adjunct should
      consider utilizing it in operating rooms for BR as part of a horizontal infection
      prevention surgical site infection-reduction strategy.

PMID- 28431852
TI  - How well does transfer of bacterial pathogens by culture swabs correlate with
      transfer by hands?
AB  - In laboratory testing and in isolation rooms, pickup and transfer of health care
      associated pathogens by premoistened rayon swabs correlated well with pickup and
      transfer by bare hands or moistened gloves. These results suggest that swab
      cultures provide a useful surrogate indicator of the risk for pathogen pickup and
      transfer by hands.

PMID- 28431853
TI  - Transmission of methicillin-resistant Staphylococcus aureus to health care worker
      gowns and gloves during care of residents in Veterans Affairs nursing homes.
AB  - BACKGROUND: This was an observational study designed to estimate the frequency of
      methicillin-resistant Staphylococcus aureus (MRSA) transmission to gowns and
      gloves worn by health care workers (HCWs) interacting with Veterans Affairs
      Community Living Center (VA nursing home) residents to inform MRSA prevention
      policies. METHODS: Participants included residents and HCWs from 7 VA nursing
      homes in 4 states and Washington, DC. Residents were cultured for MRSA at the
      anterior nares, perianal skin, and wound (if present). HCWs wore gowns and gloves
      during usual care activities. After each activity, a research coordinator swabbed
      the HCW's gown and gloves. Swabs were cultured for MRSA. RESULTS: There were 200
      residents enrolled; 94 (46%) were MRSA colonized. Glove contamination was higher
      than gown contamination (20% vs 11%, respectively; P < .01). Transmission varied
      greatly by type of care from 0%-19% for gowns and 7%-37% for gloves. High-risk
      care activities (odds ratio [OR] > 1.0, P < .05) for gown contamination included
      changing dressings (eg, wound), dressing, providing hygiene (eg, brushing teeth),
      and bathing. Low-risk care activities (OR < 1.0, P < .05 or no transmission) for
      gown contamination included glucose monitoring, giving medications, and feeding.
      CONCLUSIONS: MRSA transmission from colonized residents to gloves was higher than
      transmission to gowns. Transmission to gloves varies by type of care, but all
      care had a risk of contamination, demonstrating the importance of hand hygiene
      after all care. Transmission to gowns was significantly higher with certain types
      of care. Optimizing gown and glove use by targeting high-risk care activities
      could improve resident-centered care for MRSA-colonized residents by promoting a
      home-like environment.

PMID- 28431854
TI  - Relationship of cotinine-verified and self-reported smoking status with metabolic
      syndrome in 116,094 Korean adults.
AB  - BACKGROUND: No study has reported the relationship between cotinine-verified and
      self-reported smoking status with metabolic syndrome (MetS). OBJECTIVE: This
      study was performed to evaluate the relationship between urinary cotinine
      verified and self-reported smoking status with MetS and determine the effects of
      unobserved smokers on MetS in Korean adults. METHODS: A total of 116,094
      individuals (66,875 men and 49,219 women) with mean age of 36.7 +/- 6.8 years
      included in Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study between
      2011 and 2013 who had urinary cotinine measurements were enrolled. Cotinine
      verified current smoking was defined as urinary cotinine level of above 50 ng/mL.
      Unobserved smoking was defined as urinary cotinine level of above 50 ng/mL in
      self-reported never smokers. RESULTS: The overall prevalence rates of cotinine
      verified current smokers and MetS were 22.9% and 10.5%, respectively. The
      misclassification rate to cotinine-verified current smokers among self-reported
      never smokers was 1.7%. A multivariate logistic regression model adjusted for
      variables with univariate relationship (model 1) showed that cotinine-verified
      current smokers significantly increased the odds ratio for MetS compared with
      cotinine-verified never smokers (odds ratio [95% confidence interval], 1.30
      [1.23, 1.37]). Log-transformed cotinine levels were also associated with MetS
      (1.04 [1.03, 1.05]). However, the association was not significant in the
      previously mentioned model including the traditional 5 components of MetS (model
      2). Unobserved smokers significantly increased the ORs for MetS in both model 1
      (1.43 [1.23, 1.67]) and model 2 (1.57 [1.06, 2.33]). CONCLUSION: This study shows
      that unobserved smoking and cotinine-verified current smoking are associated with
      MetS but urinary cotinine could be 1 conditional factor that interacts with
      traditional MetS components.

PMID- 28431855
TI  - Relationship between long noncoding RNAs and physiological risk factors of
      cardiovascular disease.
AB  - Long noncoding ribonucleic acids (lncRNAs) are an important category of noncoding
      RNAs that play crucial roles in controlling the expression of genes in health and
      in a range of illnesses including cardiovascular disease. A large body of
      genetic, experimental, and epidemiologic evidence suggests roles for an
      increasing number of lncRNAs in the regulation of metabolism, lipid profile,
      inflammation, and glucose metabolism in type II diabetes. Importantly, it has
      been suggested that lncRNAs can regulate chromatin alteration, messenger RNA
      stability, microRNA action, and can control transcription factors. We aimed to
      highlight emerging concepts, based on the most current knowledge, regarding the
      roles of lncRNA in the regulation of cardiovascular risk factors such as lipid
      profile, glucose homeostasis, and inflammation.

PMID- 28431856
TI  - Patients with low-risk cutaneous squamous cell carcinoma do not require extended
      out-patient follow-up.

PMID- 28431857
TI  - Modeling human infertility with pluripotent stem cells.
AB  - Human fertility is dependent upon the correct establishment and differentiation
      of the germline. This is because no other cell type in the body is capable of
      passing a genome and epigenome from parent to child. Terminally differentiated
      germline cells in the adult testis and ovary are called gametes. However, the
      initial specification of germline cells occurs in the embryo around the time of
      gastrulation. Most of our knowledge regarding the cell and molecular events that
      govern human germline specification involves extrapolating scientific principles
      from model organisms, most notably the mouse. However, recent work using next
      generation sequencing, gene editing and differentiation of germline cells from
      pluripotent stem cells has revealed that the core molecular mechanisms that
      regulate human germline development are different from rodents. Here, we will
      discuss the major molecular pathways required for human germline differentiation
      and how pluripotent stem cells have revolutionized our ability to study the
      earliest steps in human embryonic lineage specification in order to understand
      human fertility.

PMID- 28431858
TI  - Third trimester preterm and term premature rupture of membranes: Is there any
      difference in maternal characteristics and pregnancy outcomes?
AB  - BACKGROUND: The clinical significance and management of preterm premature rupture
      of membranes (PPROM) remains a topic of a controversy. Although PROM is
      associated with a low rate of complications, PPROM may lead to significant
      neonatal and maternal morbidity. METHODS: We performed a retrospective study of
      714 women who presented to Jiangsu Province Hospital with third trimester PPROM
      or PROM between January and December 2015. The data were analyzed by SPSS; the
      significance of maternal characteristics, and maternal and neonatal outcomes were
      tested using Student's t test and the chi2 test. A two-sided p value < 0.05 was
      considered statistically significant. RESULTS: There were 714 women included in
      this analysis. We identified 577 (80.8%) women with PROM and 137 (19.2%) with
      PPROM. In the PPROM group, we further divided the women into 28+0-31+6 weeks (n =
      21) and 32+0-36+6 weeks (n = 116) of gestational age. PPROM was associated with a
      significantly lower gestational age, and patients in this group showed higher C
      reactive protein and body temperature when admitted to the hospital (p < 0.05).
      Breech presentation and history of previous cesarean section were associated with
      occurrence of PPROM compared with PROM (p < 0.05). The PPROM group showed a
      significantly longer latency period compared with the PROM group, in which the
      latency period increased with the lower gestational age (28+0-31+6 weeks).
      Significantly higher neonatal intensive care unit (NICU) admission rate was shown
      in the PPROM group as compared with the PROM group, and gestational age 28+0-31+6
      weeks yielded a significantly higher rate of NICU admission than 32+0-36+6 weeks
      did (p < 0.05). CONCLUSION: Higher C-reactive protein and body temperature in the
      PPROM group suggest an asymptomatic infection that requires close monitoring to
      prevent any adverse effect on pregnancy outcome. Longer latency period in PPROM
      group is predictable in order to minimize perinatal morbidity and mortality
      because of prematurity itself. Therefore, an increase in gestational age plays an
      important role that can affect a clinician's decision making regarding whether to
      transfer to the NICU.

PMID- 28431859
TI  - MRI-based quantification of renal perfusion in mice: Improving sensitivity and
      stability in FAIR ASL.
AB  - PURPOSE: The importance of the orientation of the selective inversion slice in
      relation to the anatomy in flow-sensitive alternating inversion recovery arterial
      spin labeling (FAIR ASL) kidney perfusion measurements is demonstrated by
      comparing the standard FAIR scheme to a scheme with an improved slice selective
      control experiment. METHODS: A FAIR ASL method is used. The selective inversion
      preparation slice is set perpendicular to the measurement slice to decrease the
      unintended labeling of arterial spins in the control experiment. A T1*-based
      quantification method compensates for the effects of the imperfect inversion on
      the edge of the selective inversion slice. The quantified perfusion values are
      compared to the standard experiment with parallel orientation of imaging and
      selective inversion slice. RESULTS: Perfusion maps acquired with the
      perpendicular inversion slice orientation show higher sensitivity compared to the
      parallel orientation. The T1*-based quantification method removes artifacts
      arising from imperfect inversion slice profiles. The stability is improved.
      CONCLUSION: Adjusting the labeling technique to the anatomy is of high
      importance. Improved sensitivity and reproducibility could be demonstrated. The
      proposed method provides a solution to the problem of FAIR ASL measurements of
      renal perfusion in coronal view.

PMID- 28431860
TI  - Predictive value of perfusion defects on dual energy CTA in the absence of
      thromboembolic clots.
AB  - BACKGROUND: To determine the predictive value of volumetrically measured lung
      perfusion defects (PDvol) and right ventricular dysfunction on dual-energy
      computed tomography angiography (DE-CTA) for predicting all cause mortality in
      patients suspected of pulmonary embolism (PE) but without evident thromboembolic
      clot on CTA. METHODS: 448 patients underwent DE-CTA on a 64-channel DSCT system
      between January 2007 and December 2012 for suspected PE, of which 115 were
      without detectable thromboembolic clot on CTA. Diagnostic performance for
      identifying patients at risk of dying was evaluated using ROC analysis. All-cause
      mortality was assessed via the hospital electronic medical records and/or
      consultation of the patient or the patient's primary care physician via phone
      call interviews. Sensitivity, specificity, positive likelihood ratio, negative
      likelihood ratio and area under the curve (AUC) were determined for PDvol (volume
      of perfusion defects/total lung volume), transverse right ventricular to left
      ventricular diameter ratios (RV/LV) and for the combination of both tests.
      RESULTS: Mortality was 38% within the investigated time period of 6 months.
      Patients who died had significantly higher PDvol (PDvol 28 +/- 13% vs. 19 +/-
      12%, p < 0.001) and a non-significant difference in transverse RV/LV ratio (1.14
      +/- 0.37 vs. 1.06 +/- 0.22, p = 0.159). The AUC was 0.71 for PDvol, 0.53 for
      RV/LV ratio, and 0.67 for the combination of PDvol and RV/LV ratio. PDvol
      remained a significant predictor after correcting for age. CONCLUSIONS: In the
      absence of thromboembolic clots, PDvol at DE-CTA appears to be predictive for all
      cause mortality.

PMID- 28431861
TI  - Cardiac computed tomography-derived myocardial mass at risk using the Voronoi
      based segmentation algorithm: A histological validation study.
AB  - BACKGROUND: Myocardial mass at risk (MMAR) is an important predictor of adverse
      cardiac events in patients with ischemic heart disease. This study aims to
      validate the accuracy of MMAR calculated from cardiac computed tomography (CCT)
      data using the Voronoi-based segmentation algorithm in comparison with actual
      MMAR measured on ex-vivo swine hearts prepared by injecting a dye into the
      coronary arteries. METHODS: Fifteen extracted swine hearts had India ink injected
      into one of the major coronary arteries. Subsequently, all coronary arteries
      manually injected with methylcellulose-based iohexiol-370 were imaged by 16-row
      CT. The ventricles were cross-sectioned perpendicularly to the long axis of the
      left ventricle (LV). The stained area and the total LV area of individual slices
      were measured, and actual MMAR was calculated as the ratio of the LV volume with
      the disc-summation method. CT-based MMAR of each coronary artery was calculated
      automatically with the Voronoi-based segmentation algorithm. The results were
      compared using Pearson's correlation coefficient. RESULTS: The median value of CT
      based MMAR was 50.8% for the left anterior descending artery (LAD), 36.6% for the
      left circumflex artery (LCX), and 23.0% for the right coronary artery (RCA).
      Actual MMAR was 49.8% for LAD, 32.2% for LCX, and 25.9% for RCA. CT-based MMAR
      was significantly related to actual MMAR (r = 0.92, p = 0.02 for LAD; r = 0.96, p
      = 0.009 for LCX; r = 0.96, p = 0.009 for RCA). CONCLUSION: CT-based MMAR obtained
      by Voronoi-based segmentation algorithm reliably estimates actual MMAR measured
      on ex-vivo swine hearts.

PMID- 28431862
TI  - Application of the CDC EbolaResponse Modeling tool to disease predictions.
AB  - Model-based predictions were critical in eliciting a vigorous international
      public health response to the 2014 Ebola Virus Disease outbreak in West Africa.
      Here, we describe the performances of an extension of the CDC-initiated
      EbolaResponse Modeling tool to the Ebola Forecasting Challenge, which offered a
      controlled environment for epidemiological predictions. In the EbolaResponse
      tool, transmission risks and proportions of population affected by interventions
      were fitted to data via least square fitting. Prediction performances were
      evaluated for 5 prediction time points of 4 synthetic outbreaks. One-to-four week
      ahead incidence predictions were well correlated with synthetic observations (rho
      ~0.8), and overall ranking averaged over various error metrics was 4th of 8 teams
      participating in the context. EbolaResponse yielded moderately accurate
      predictions for final size, peak size and timing. The relative success of this
      easily adaptable mechanistic model, with reassessment of model parameters at
      fixed intervals, indicates that it can generate relatively accurate short-term
      forecasts, especially when interventions are staggered. An important downside of
      the model includes a lack of uncertainty estimates in its current framework.
      Overall, our results align with the conclusion that simple models with few
      parameters perform well for short-term prediction of epidemic trajectories.

PMID- 28431863
TI  - The myometrial contractility during late pregnancy in dairy cows, in vitro.
AB  - This study aimed to investigate the in vitro contractility of the myometrium and
      its relationship to the blood concentrations of estradiol-17beta (E2beta),
      progesterone (P4), 15-keto-13,14-dihydro-PGF2alpha (PGFM) and ionised calcium
      (Ca2+) prior to tissue harvest in 12 healthy Holstein-Friesian cows in late
      pregnancy. Three circular (CM) and 3 longitudinal myometrial (LM) strips were
      dissected during a caesarean section and mounted in an organ bath containing
      modified Krebs solution (KS). The spontaneous contractility was recorded during
      five 30-min time periods (T1 to T5), after which the strips were exposed to
      increasing concentrations of oxytocin (OT; 10-10-10-7M), a natural PGF2alpha
      analogue (PGF; 10-7-10-4M) and KS (Cont) for four 30-min time periods (T6 to T9).
      The variables area under the curve (AUC), mean (MA) and maximal amplitude (maxA)
      were calculated for each T. The blood P4, E2beta, Ca2+ and PGFM values averaged
      4.0+/-1.7ng/mL, 482.3+/-63.7 pg/mL, 0.8+/-0.3 mmol/L and 125.3+/-63.7pg/mL. The
      LM strips had greater AUC, MA, and maxA than CM, and OT caused greater AUC and MA
      in both muscle layers than PGF or control treatment (OT>PGF>Cont). Estradiol
      17beta correlated with AUC and MA of LM at T1 to T5 (r=0.69; P<=0.05). In
      conclusion, LM and CM strips have different contractile performance but show
      enhanced activity when stimulated with OT and less activity after PGF stimulation
      if compared with Cont. Blood concentrations of E2beta may be useful as an
      indicator of uterine contractile performance in late pregnant cattle.

PMID- 28431864
TI  - Toward an integrative and predictive sperm quality analysis in Bos taurus.
AB  - There is a need to develop more integrative sperm quality analysis methods,
      enabling researchers to evaluate different parameters simultaneously cell by
      cell. In this work, we present a new multi-parametric fluorescent test able to
      discriminate different sperm subpopulations based on their labeling pattern and
      motility characteristics. Cryopreserved semen samples from 20 Holstein bulls were
      used in the study. Analyses of sperm motility using computer-assisted sperm
      analysis (CASA-mot), membrane integrity by acridine orange-propidium iodide
      combination and multi-parametric by the ISAS(r)3Fun kit, were performed. The new
      method allows a clear discrimination of sperm subpopulations based on membrane
      and acrosomal integrity, motility and morphology. It was also possible to observe
      live spermatozoa showing signs of capacitation such as hyperactivated motility
      and changes in acrosomal structure. Sperm subpopulation with intact plasma
      membrane and acrosome showed a higher proportion of motile sperm than those with
      damaged acrosome or increased fluorescence intensity. Spermatozoa with intact
      plasmalemma and damaged acrosome were static or exhibit weak movement.
      Significant correlations among the different sperm quality parameters evaluated
      were also described. We concluded that the ISAS(r)3Fun is an integrated method
      that represents an advance in sperm quality analysis with the potential to
      improve fertility predictions.

PMID- 28431865
TI  - Statin use and other factors associated with mortality after major lower
      extremity amputation.
AB  - OBJECTIVE: Above-knee amputations (AKAs) and below-knee amputations (BKAs) are
      associated with high postoperative mortality rates. In this study, we examined
      factors associated with 30-day, 90-day, and 1-year mortality in patients who
      underwent a major lower extremity amputation. METHODS: We queried a prospectively
      collected institutional database for all patients who underwent AKA or BKA with
      primary or secondary closure, during a 5-year period, between November 2009 and
      November 2014. Predictors of 30- and 90-day mortality were determined by
      multivariable logistic regression, and risk indexes for 1-year mortality were
      determined with Cox proportional hazards model. RESULTS: We identified 811
      patients who underwent AKA (n = 325) or BKA (n = 486). The 30-day mortality was
      8.4% (AKA, 13.5%; BKA, 4.9%; P < .001) and 90-day mortality was 15.4% (AKA,
      24.3%; BKA, 9.45%; P < .001). Predictors of 30-day mortality included AKA (odds
      ratio [OR], 3.09; 95% confidence interval [CI], 1.76-5.53), emergency operation
      (OR, 2.86; 95% CI, 1.56-5.14), chronic obstructive pulmonary disease (OR, 3.09;
      95% CI, 1.07-7.81), end-stage renal disease (ESRD) on hemodialysis (HD; OR, 2.35;
      95% CI, 1.24-4.33), and chronic kidney disease stages 3 (OR, 1.84; 95% CI, 1.00
      3.37) and 4 (OR, 2.33; 95% CI, 1.01-4.98). Predictors of 90-day mortality
      included age (OR, 1.02; 95% CI, 1.00-1.04), ESRD on HD (OR, 2.56; 95% CI, 1.55
      4.22), AKA (OR, 2.61; 95% CI, 1.70-4.05), history of coronary artery bypass
      grafting (OR, 2.04; 95% CI, 1.06-3.87), and medium-intensity or high-intensity
      statin (OR, 0.46; 95% CI, 0.29-0.73). One-year survival for the overall cohort
      was 73.7% (95% CI, 70.8%-76.8%). Predictors of 1-year mortality included AKA
      (hazard ratio [HR], 2.07; 95% CI, 1.54-2.77), coronary artery bypass grafting
      (HR, 1.57; 95% CI, 1.07-2.32), age >70 years (HR, 1.39; 95% CI, 1.02-1.88),
      gangrene (HR, 1.44; 95% CI, 1.07-1.94), ESRD on HD (HR, 1.96; 95% CI, 1.42-2.70),
      chronic obstructive pulmonary disease (HR, 2.54; 95% CI, 1.52-4.25), Caucasian
      race (HR, 1.62; 95% CI, 1.18-2.22), history of open lower extremity
      revascularization (HR, 0.71; 95% CI, 0.51-1.00) and undergoing bilateral
      amputations (HR, 2.10; 95% CI, 1.06-4.15). In the year after amputation, medium
      intensity statin (HR, 0.64; 95% CI, 0.47-0.87) and high-intensity statin (HR,
      0.56; 95% CI, 0.33-0.95) conferred a mortality benefit. Low-intensity statins did
      not confer protection from mortality. At 1 year after amputation, only 44.7% of
      patients were receiving appropriate statin therapy. CONCLUSIONS: AKA and BKA have
      historically been associated with high mortality rates. Medium-intensity and high
      intensity statin therapies were associated with a mortality benefit at 1 year. We
      have identified initiation of statin therapy in this high-risk population as a
      gap in patient care.

PMID- 28431866
TI  - Circulating microRNAs signature correlates with positive [18F]fluorodeoxyglucose
      positron emission tomography in patients with abdominal aortic aneurysm.
AB  - BACKGROUND: Prediction of abdominal aortic aneurysm (AAA) rupture is a
      challenging issue. Small noncoding microRNAs (miRNAs) are potent regulators of
      gene expression and are considered as valuable circulating biomarkers. Recently,
      [18F]fluorodeoxyglucose (FDG) uptake detected by positron emission tomography
      (PET) in AAA was correlated with cellular and molecular alterations involved in
      wall instability and its potential rupture. Our study aimed at identifying
      circulating miRNAs correlated with a positive PET that could help discriminate
      patients at high risk of rupture. METHODS: The level of 372 miRNAs was evaluated
      by polymerase chain reaction array in plasma from 35 AAA patients displaying no
      FDG uptake (A0) and 22 patients with a positive PET uptake (A+). The modulated
      miRNAs were validated by quantitative polymerase chain reaction and measured in
      aneurysmal tissues from both groups of patients. RESULTS: Six circulating miRNAs
      were found significantly modulated in A+ vs A0 patients. They were significantly
      correlated not only between them but also with the intensity of FDG uptake. Two
      of them correlated also with the AAA diameter. These miRNAs displayed significant
      discriminating power between the A+ and A0 groups as determined by receiver
      operating characteristic curves. Three downregulated circulating miRNAs (miR-99b
      5p, miR-125b-5p, and miR-204-5p) were also significantly reduced in the
      aneurysmal tissue, specifically in the FDG-uptake site, compared with a negative
      zone in the same aneurysm and with A0 aneurysms. They were further significantly
      inversely correlated with the expression, at the positive uptake site, of some of
      their potential gene targets, most notably matrix metalloproteinase 13.
      CONCLUSIONS: Six miRNAs were identified as potential new circulating biomarkers
      of PET+ AAA. Three of these were similarly modulated in the metabolically active
      aneurysmal wall and might be directly involved in AAA instability.

PMID- 28431868
TI  - A Longitudinal Analysis of Quality of Life and Associated Factors in Older Adults
      with Schizophrenia Spectrum Disorder.
AB  - OBJECTIVES: Self-perceived quality of life (QOL) is an important outcome
      indicator in schizophrenia and a predictor of symptomatic and functional
      improvement. This study provides the first large scale longitudinal study of the
      fluctuations, predictors, and impact of QOL in older adults with schizophrenia
      spectrum disorder (SSD). METHODS: The sample consisted of 104 community-dwelling
      persons with SSD aged 55 and over (mean age: 61years) who developed the disorder
      prior to age 45. Mean follow-up was 52.5 months (range 12-116 months); 55% were
      men; 55% were white. We identified 22 potential predictor variables and used the
      Quality of Life Index (QLI) to assess QOL. RESULTS: There were no significant
      group differences in the QLI at baseline and follow-up. However, 33%, 24% and 43%
      of persons exhibited > 0.5 effect size increase or decrease, or no change,
      respectively. In multivariable analysis, there were 5 baseline predictors of QLI
      at follow-up: QLI, Center for Epidemiological Studies-Depression Scale (CES-D)
      scores, religiousness, perceived well-being versus others/past self, and time
      from initial interview. Baseline QLI predicted 5 variables at follow-up: the
      Positive and Negative Syndrome Scale (PANSS) anxiety score, PANSS positive score,
      CES-D score, insight, and perceived well-being versus others/past self.
      CONCLUSION: In many persons with SSD, QOL is not static in later life and one
      third improved their QOL. Effectively treating depressive symptoms and
      encouraging religious participation may improve QOL. QOL had two pivotal roles:
      As a relatively independent dynamic outcome measure and as a critical variable
      affecting clinical outcomes such as anxiety, depressive and positive symptoms.

PMID- 28431867
TI  - Whole exome sequencing identification of novel candidate genes in patients with
      proliferative diabetic retinopathy.
AB  - Rare or novel gene variants in patients with proliferative diabetic retinopathy
      may contribute to disease development. We performed whole exome sequencing (WES)
      on patients at the phenotypic extremes of diabetic retinal complications: 57
      patients diagnosed with proliferative diabetic retinopathy (PDR) as cases and 13
      patients with no diabetic retinopathy despite at least 10years of type 2 diabetes
      as controls. Thirty-one out of the 57 cases and all 13 controls were from the
      African American Proliferative Diabetic Retinopathy Study (AA). The rest of the
      cases were of mixed ethnicities (ME). WES identified 721 candidate genes with
      rare or novel non-synonymous variants found in at least one case with PDR and not
      present in any controls. After filtering for genes with null alleles in greater
      than two cases, 28 candidate genes were identified in our ME cases and 16 genes
      were identified in our AA cases. Our analysis showed rare and novel variants
      within these genes that could contribute to the development of PDR, including
      rare non-synonymous variants in FAM132A, SLC5A9, ZNF600, and TMEM217. We also
      found previously unidentified variants in VEGFB and APOB. We found that VEGFB,
      VPS13B, PHF21A, NAT1, ZNF600, PKHD1L1 expression was reduced in human retinal
      endothelial cells (HRECs) cultured under high glucose conditions. In an exome
      sequence analysis of patients with PDR, we identified variants in genes that
      could contribute to pathogenesis. Six of these genes were further validated and
      found to have reduced expression in HRECs under high glucose conditions,
      suggestive of an important role in the development of PDR.

PMID- 28431869
TI  - The diagnostic and prognostic value of the optic nerve sheath diameter on CT for
      diagnosis spontaneous subarachnoid hemorrhage.
AB  - INTRODUCTION: The aim of this study was to investigate the relationship between
      the optic nerve sheath diameter (ONSD) measured on non-contrast head computed
      tomography (CT) and the diagnosis and prognosis of spontaneous subarachnoid
      hemorrhage (SAH) on emergency department (ED) patients. METHOD: We used a matched
      control group of patients with the same age and gender who were diagnosed in the
      ED with spontaneous SAH and who admitted to the ED with headache. Four emergency
      medicine attending physicians made the ONSD measurements. For measurements, the 3
      mm posterior location where the optic nerve enters the eyeball was used. RESULTS:
      This study was done with 61 spontaneous SAHs with an equal number of control
      patients. The median ONSD for control and spontaneous SAH groups was 5.76
      [interquartile range (IQR): 0.96] mm and 6.72 (IQR: 1.42) mm, respectively
      (p<0.001). The area under the receiver operating characteristic curve was
      determined as 0.791 (confidence interval 95% 0.710-0.872). At an ONSD threshold
      value of 6.1 mm, the sensitivity and specificity of SAH was 72%. There was no
      significant relationship between ONSD and in-hospital mortality in spontaneous
      SAH patients (p>0.05). The intra-class correlation coefficients for inter and
      intra-rater reliability were 0.84 and 0.95, respectively. CONCLUSION: In patients
      with spontaneous SAH, the ONSD measured in the orbital sections of a head CT is
      strongly correlated with a SAH diagnosis. Assessment of ONSD in head CTs taken
      with spontaneous SAH suspicion may contribute to the diagnoses of spontaneous
      SAH.

PMID- 28431870
TI  - The effect of hypertonic saline and mannitol on coagulation in moderate traumatic
      brain injury patients.
AB  - BACKGROUND: Hyperosmolar therapy, using either hypertonic saline (HTS) or
      mannitol (MT), is considered the treatment of choice for intracranial
      hypertension, a disorder characterized by high intracranial pressure (ICP).
      However, hyperosmolar agents have been postulated to impair coagulation and
      platelet function. The aim of this study was to identify whether HTS and MT could
      affect coagulation in moderate traumatic brain injury (TBI) patients. METHODS: In
      this prospective and randomized double-blind study, we included adult patients
      with moderate TBI. Patients were divided into two groups according to the type of
      hypertonic solution administered. Group A patients received 20% MT and group B
      patients received 3% HTS. Rotational thromboelastometry (ROTEM) parameters were
      used to assess coagulation and platelet function. RESULTS: ROTEM parameters
      included CT (clotting time), CFT (clot formation time), maximum clot firmness
      (MCF) measured by MCF (EXTEM and INTEM), MCF (FIBTEM) and standard coagulation
      tests (p>0.05). No significant differences were found between the two groups.
      Moreover, ROTEM parameters did not show significant changes at different time
      points after administration of the hyperosmolar solutions (p>0.05). Conclusions
      Overall, use of 3% HTS and 20% MT for the control of ICP did not significantly
      affect patients' coagulation function. Therefore, hyperosmotic solution is safe
      and does not increase the risk of intracranial rebleeding.

PMID- 28431871
TI  - How do EMS medical directors think?

PMID- 28431872
TI  - Plasma copeptin levels in the patients with gastrointestinal bleeding.
AB  - INTRODUCTION: Gastrointestinal bleeding is a significant cause of morbidity and
      mortality worldwide. In addition, it constitutes an important part of health
      expenditures. In this study, we aimed to determine whether there is a
      relationship between plasma copeptin levels and the etiology, location and
      severity of gastrointestinal bleeding. MATERIALS AND METHODS: This study was
      performed prospectively in 104 consecutive patients who were admitted to an
      emergency department with complaints of bloody vomiting or bloody or black stool.
      To evaluate the level of biochemical parameters such as Full Blood Count (FBC),
      serum biochemistry, bleeding parameters and copeptin, blood samples were obtained
      at admission. For the copeptin levels, 2 more blood samples were obtained at the
      12th and 24th hours after admission. The values obtained were compared using
      statistical methods. RESULTS: In terms of the etiology of bleeding, the copeptin
      levels in the patients with peptic ulcer were higher than the levels in patients
      with other gastrointestinal bleeding. However, the difference was not
      statistically significant. There were no significant differences among all
      groups' 0th, 12th and 24th hour levels of copeptin. DISCUSSION: We conclude that
      copeptin cannot be effectively used as a biochemical parameter in an emergency
      department to determine the etiology and location of gastrointestinal bleeding.
      It can, however, be used to make decisions on endoscopy and the hospitalization
      of patients with suspected gastrointestinal bleeding.

PMID- 28431873
TI  - A novel clinical index for the assessment of RVD in acute pulmonary embolism:
      Blood pressure index.
AB  - BACKGROUND: This study aims to investigate the role of the blood pressure index
      (BPI), which is a new index that we developed, in detection of right ventricular
      dysfunction (RVD) in acute pulmonary embolism (APE). METHODS: A total of 539
      patients, (253 males and 286 females), diagnosed with APE using computer
      tomography pulmonary angiography were included in the study. The BPI was obtained
      by dividing systolic blood pressure (SBP) by diastolic blood pressure (DBP).
      RESULTS: Mean DBP (75+/-11mmHg vs 63+/-15mmHg; p<0.001, respectively) was found
      to be higher in RVD patients compared to those without RVD, whereas BPI (1.5+/
      0.1 vs 1.9+/-0.2; p<0.001, respectively) was lower. Examining the performance of
      BPI in prediction of RVD using receiver operating characteristic curve analysis
      (area under curve+/-SE=0.975+/-0.006; p<0.001), it was found that BPI could
      predict RVD with very high sensitivity (92.8%) and specificity (100%) and had a
      positive predictive value of 100% and a negative predictive value of 42.1%.
      According to the analysis, the highest youden index for the optimal prediction
      value was found to be 0.478 and the BPI<=1.4 was found to predict mortality 68.6%
      sensitivity and 80.8% specificity (Area under curve+/-SE=0.777+/-0.051; p<0.001).
      CONCLUSIONS: We found that BPI was an index with high positive predictive value
      and low negative predictive value in detection of RVD.

PMID- 28431874
TI  - Regional disparities in the quality of stroke care.
AB  - BACKGROUND AND PURPOSE: There is widespread geographic variation in healthcare
      quality, but we often lack clear strategies for improving quality in underserved
      areas. This study characterized geographic disparities in stroke care quality to
      assess whether improved access to neurological services has the potential to
      bridge the care quality gap, particularly in terms of alteplase (rt-PA)
      administration. METHODS: This was a retrospective study using quality performance
      data from the 2015 Hospital Compare database linked to information on
      certification status from the Joint Commission and information on local access to
      neurological services from the Area Health Resources File. We used these data to
      compare stroke care quality according to geographic area, certification, and
      neurologist access. RESULTS: Non-metropolitan hospitals performed worse than
      metropolitan hospitals on all assessed stroke care quality measures. The most
      prevalent disparity occurred in the use of rt-PA for eligible patients (52.2%
      versus 82.7%, respectively). Certified stroke centers in every geographic
      designation provided higher quality of care, whereas large variation was observed
      among non-certified hospitals. Regression analyses suggested that improvements in
      hospital certification or access to neurologists were associated with absolute
      improvements of 44.9% and 21.3%, respectively, in the percentage of patients
      receiving rt-PA. CONCLUSIONS: The large quality gap in stroke care between
      metropolitan and non-metropolitan areas could be at least partly addressed
      through improved procedural efforts by stroke center certification increasing the
      supply of neurological services, (i.e. through training and hiring new
      neurologists) or by adopting decision support systems such as telemedicine.

PMID- 28431875
TI  - Proteins oxidation and autoantibodies' reactivity against hydrogen peroxide and
      malondialdehyde -oxidized thyroid antigens in patients' plasmas with Graves'
      disease and Hashimoto Thyroiditis.
AB  - The aim of this study was to evaluate proteins oxidation in plasmas of two
      autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto
      Thyroiditis (HT), and to determine whether oxidative modification of thyroid
      antigens (T.Ag) enhanced the reactivity of autoantibodies in plasmas of AITD
      patients compared with the reactivity towards native T.Ag. Carbonyl and thiol
      groups and MDA-protein adducts were assessed spectrophotometric methods in
      plasmas of 74 AITD patients and 65 healthy controls. The reactivities
      immunoglobulin (Ig)G autoantibodies towards malondialdehyde (MDA)-modified T.Ag,
      hydrogen peroxide (H2O2)-modified T.Ag, native T.Ag and native derm were checked
      by enzyme-linked immunosorbent assay (ELISA). Evaluation of oxidized proteins
      exhibited high levels of MDA bound to proteins and carbonyl groups, as well as
      reduced thiol level in plasmas of AITD patients by comparison to healthy controls
      (p < 0.05). The ELISA test showed that AITD patients' plasmas' reactivity to
      native T.Ag was significantly increased to the reactivity towards native derm,
      whereas, no differences were found in the reactivity to native T.Ag and derm in
      controls plasmas. In addition, treatment of T.Ag by oxidants revealed enhanced
      reactivity of IgG circulating autoantibodies against H2O2-oxidized T.Ag compared
      to native ones (p < 0.001) in plasmas of both AITD. Also, reactivity's to MDA
      oxidized T.Ag in GD plasmas decreased compared to native ones (p < 0.05) and no
      changes were noted for HT. Pearson correlation study resulted in positive
      correlation between reactivity's to H2O2-oxidized T.Ag and free triodotyronine
      level in GD patients (r = 0.42, p < 0.05) in one hand and thyroid stimulating
      hormone level in HT patients in the other (r = 0.65, p < 0.001). The data suggest
      that high production of H2O2 probably occurred during hormone synthesis could
      contribute to protein oxidation in AITD and to create neoepitopes responsible for
      autoantibody reactivity's to H2O2-oxidized T.Ag enhancement. These results
      provide support to the involvement of oxidative stress in AITD development and/or
      exacerbation.

PMID- 28431876
TI  - Role of the locus coeruleus catecholaminergic neurons in the chemosensory control
      of breathing in a Parkinson's disease model.
AB  - A previous study has demonstrated that in the 6-hydroxydopamine (6-OHDA)-model of
      Parkinson's disease (PD) there is a reduction in the number of Phox2b neurons in
      the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to
      hypercapnia 40days after PD-induction. The functional deficiency is restored
      60days after 6-OHDA injection and here we tested the hypothesis that the locus
      coeruleus (LC) could be a candidate to restore the breathing deficiency. Minute
      Ventilation (VE) in response to hypercapnia (7% CO2) was assessed one day before,
      and then 40 and 60days after bilateral 6-OHDA (24MUg/MUL) or vehicle injections
      into the LC in control or PD-induced male Wistar rats. Bilateral injections of 6
      OHDA decreased catecholaminergic neurons by 86% and 83% in the substantia nigra
      pars compacta (SNpc) and LC, respectively. As already described, in animals with
      lesions to the SNpc (N=6/group), the reduction in the ventilatory response to
      hypercapnia was restored 60days after PD (1257+/-81 vs. vehicle: 1185+/
      49mL/kg/min). However, in animals with PD and lesion in the LC, the ventilation
      was blunted (674+/-39mL/kg/min). In another group of PD rats, we observed a
      reduction in the number of hypercapnia-induced-fos+ cells in the RTN region
      (40days: 38+/-3 and 60days: 8.5+/-0.9 vs. vehicle 78+/-3 cells) and an increase
      in the LC (40days: 46+/-4 and 60days: 94+/-22 vs. vehicle 1+/-1 cells). Our data
      suggest that LC catecholaminergic neurons can be a candidate structure mediating
      chemoreceptor function in a model of PD.

PMID- 28431877
TI  - Synthesis and evaluation of pyridinium polyoxometalates as anti-HIV-1 agents.
AB  - The unique properties of polyoxometalates, such as molecular polarity, redox
      potential, surface charge distribution, shape and acidity, influence their
      response of recognition to targeted biological macromolecules. By using PM-19
      (K7PTi2W10O40) as a lead-compound, a series of novel pyridinium polyoxometalates
      (A7PTi2W10O40), which hadn't been reported in literatures, were designed and
      synthesized. The evaluation was conducted using the single-cycle pseudovirus
      infection assay (TZM-bl assay), CCK-8 method was used for determining the
      cytotoxicity. The results indicated that the designed pyridinium polyoxometalates
      had a lower toxicity to TZM-bl cells, and showed higher inhibitory activity
      against HIV-1 virus.

PMID- 28431878
TI  - Design, synthesis and anticancer activity of novel nopinone-based
      thiosemicarbazone derivatives.
AB  - A series of new nopinone-based thiosemicarbazone derivatives were designed and
      synthesized as potent anticancer agents. All these compounds were identified by
      1H NMR, 13C NMR, HR-MS spectra analyses. In the in vitro anticancer activity,
      most derivatives showed considerable cytotoxic activity against three human
      cancer cell lines (MDA-MB-231, SMMC-7721 and Hela). Among them, compound 4i
      exhibited most potent antitumor activity against three cancer cell lines with the
      IC50 values of 2.79+/-0.38, 2.64+/-0.17 and 3.64+/-0.13MUM, respectively.
      Furthermore, the cell cycle analysis indicated that compound 4i caused cell cycle
      arrest of MDA-MB-231 cells at G2/M phase. The Annexin V-FITC/7-AAD dual staining
      assay also revealed that compound 4i induced the early apoptosis of MDA-MB-231
      cells.

PMID- 28431879
TI  - Improvement of hERG-ROMK index of spirocyclic ROMK inhibitors through scaffold
      optimization and incorporation of novel pharmacophores.
AB  - SAR in the previously described spirocyclic ROMK inhibitor series was further
      evolved from lead 4 by modification of the spirocyclic core and identification of
      novel right-side pharmacophores. In this process, it was discovered that the
      spiropyrrolidinone core with the carbonyl group alpha to the spirocenter was
      preferred for potent ROMK activity. Efforts aimed at decreasing hERG affinity
      within the series led to the discovery of multiple novel right-hand
      pharmacophores including 3-methoxythiadiazole, 2-methoxypyrimidine, and
      pyridazinone. The most promising candidate is pyridazinone analog 32 that showed
      an improved functional hERG/ROMK potency ratio and preclinical PK profile. In
      vivo evaluation of 32 demonstrated blood pressure lowering effects in the
      spontaneously hypertensive rat model.

PMID- 28431880
TI  - Photo-controlled release of fipronil from a coumarin triggered precursor.
AB  - Developing efficient controlled release system of insecticide can facilitate the
      better use of insecticide. We described here a first example of photo-controlled
      release of an insecticide by linking fipronil with photoresponsive coumarin
      covalently. The generated coumarin-fipronil (CF) precursor could undergo cleavage
      to release free fipronil in the presence of blue light (420nm) or sunlight.
      Photophysical studies of CF showed that it exhibited strong fluorescence
      properties. The CF had no obvious activity against mosquito larvae under dark,
      but it can be activated by light inside the mosquito larvae. The released Fip
      from CF by blue light irradiation in vitro retained its activity to armyworm
      (Mythimna separate) with LC50 value of 24.64MUmolL-1. This photocaged molecule
      provided an alternative delivery method for fipronil.

PMID- 28431881
TI  - Design and synthesis of 1,2,3-triazolo-phenanthrene hybrids as cytotoxic agents.
AB  - A series of new 1,2,3-triazolo-phenanthrene hybrids has been synthesized by
      employing Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. These
      compounds were evaluated for their in vitro cytotoxic potential against various
      human cancer cell lines viz. lung (A549), prostate (PC-3 and DU145), gastric (HGC
      27), cervical (HeLa), triple negative breast (MDA-MB-231, MDA-MB-453) and breast
      (BT-549, 4T1) cells. Among the tested compounds, 7d displayed highest
      cytotoxicity against DU145 cells with IC50 value of 1.5+/-0.09uM. Further, the
      cell cycle analysis shown that it blocks G0/G1 phase of the cell cycle in a dose
      dependent manner. In order to determine the effect of compound on cell viability,
      phase contrast microscopy, AO/EB, DAPI, DCFDA and JC-1 staining studies were
      performed. These studies clearly indicated that the compound 7d inhibited the
      cell proliferation of DU145 cells. Relative viscosity measurements and molecular
      docking studies indicated that these compounds bind to DNA by intercalation.

PMID- 28431882
TI  - [Primary carcinoma of seminal vesicle: A delayed revealed cancer].

PMID- 28431883
TI  - Primary Repair of Traumatic Distal Biceps Ruptures in a Military Population:
      Clinical Outcomes of Single- Versus 2-Incision Technique.
AB  - PURPOSE: To determine the success of distal biceps repair in a high-demand
      military population and to comparatively evaluate the perioperative risk profile,
      functional results, and adverse patient outcomes of a single- versus 2-incision
      technique within this high-risk group. METHODS: Between 2007-2013, all military
      service members undergoing primary surgical repair for distal biceps rupture
      through the Military Health System were isolated. Patients with allograft tendon
      reconstruction, revision procedures, nonmilitary status, and/or follow-up of less
      than 24 month were excluded. Demographic data (age, limb dominance) and surgical
      variables (time to surgery, surgical technique) were extracted, and rates of
      perioperative complications, rerupture, reoperation, revision, and inability to
      return to preinjury function were recorded. Logistic regression analysis was
      performed to evaluate for prognostic risk factors, whereas the Fisher exact test
      was used for comparative analysis. RESULTS: A total of 290 patients met the
      inclusion criteria, including 44 (15.2%) with a delayed presentation; all
      patients were men, with an average age of 38.9 years (range, 20-61 years). A
      single-incision technique was performed in 75.4% (n = 214) versus a 2-incision
      technique in 24.6% (n = 70), and a cortical button was the predominant fixation
      construct (73.4%). Reruptures occurred in 7 patients (2.4%), and 3 individuals
      (1.0%) had significant elbow dysfunction postoperatively. When we compared the
      overall complication rates, the 2-incision technique (7.1%, n = 5) was not
      significantly different from the single-incision repair (16.4%, n = 35; P =
      .0732). Tobacco use was significantly associated with risk of rerupture (odds
      ratio, 4.86; P = .0423) or combined surgical and clinical failures (odds ratio,
      5.64; P = .0091), whereas age, limb dominance, time to surgery, fixation
      construct, and surgical technique were not statistically significant (P > .05).
      CONCLUSIONS: Among active patients, a single-volar incision technique and a 2
      incision technique showed similar complication profiles. Rerupture and persistent
      elbow dysfunction were uncommon, but adverse outcomes were significantly more
      likely among patients who used tobacco. Anatomic distal biceps repair is a safe
      surgical procedure with excellent clinical outcomes and a 96.6% rate of return to
      preoperative military function without restrictions. LEVEL OF EVIDENCE: Level
      III, retrospective comparative study.

PMID- 28431884
TI  - Percutaneous Ventricular Assist Device for Circulatory Support During Ablation of
      Atrial Tachycardias in Patients With Fontan Circulation.

PMID- 28431885
TI  - Safety of Adding Oats to a Gluten-Free Diet for Patients With Celiac Disease:
      Systematic Review and Meta-analysis of Clinical and Observational Studies.
AB  - BACKGROUND & AIMS: Patients with celiac disease should maintain a gluten-free
      diet (GFD), excluding wheat, rye, and barley. Oats might increase the nutritional
      value of a GFD, but their inclusion is controversial. We performed a systematic
      review and meta-analysis to evaluate the safety of oats as part of a GFD in
      patients with celiac disease. METHODS: We searched the Cochrane Central Register
      of Controlled Trials, MEDLINE, and EMBASE databases for clinical trials and
      observational studies of the effects of including oats in GFD of patients with
      celiac disease. The studies reported patients' symptoms, results from serology
      tests, and findings from histologic analyses. We used the GRADE approach to
      assess the quality of evidence. RESULTS: We identified 433 studies; 28 were
      eligible for analysis. Of these, 6 were randomized and 2 were not randomized
      controlled trials comprising a total of 661 patients-the remaining studies were
      observational. All randomized controlled trials used pure/uncontaminated oats.
      Oat consumption for 12 months did not affect symptoms (standardized mean
      difference: reduction in symptom scores in patients who did and did not consume
      oats, -0.22; 95% CI, -0.56 to 0.13; P = .22), histologic scores (relative risk
      for histologic findings in patients who consumed oats, 0.24; 95% CI, 0.01-4.8; P
      = .35), intraepithelial lymphocyte counts (standardized mean difference, 0.21;
      95% CI, reduction of 1.44 to increase in 1.86), or results from serologic tests.
      Subgroup analyses of adults vs children did not reveal differences. The overall
      quality of evidence was low. CONCLUSIONS: In a systematic review and meta
      analysis, we found no evidence that addition of oats to a GFD affects symptoms,
      histology, immunity, or serologic features of patients with celiac disease.
      However, there were few studies for many endpoints, as well as limited geographic
      distribution and low quality of evidence. Rigorous double-blind, placebo
      controlled, randomized controlled trials, using commonly available oats sourced
      from different regions, are needed.

PMID- 28431886
TI  - Innate resistance of New Zealand paua to abalone viral ganglioneuritis.
AB  - The susceptibility of New Zealand paua (Haliotis iris) to infection by abalone
      herpesvirus (Haliotid herpesvirus 1; HaHV) and to the disease abalone viral
      ganglioneuritis (AVG) was determined. Infection challenges performed by intra
      muscular injection and by immersion in infectious water containing HaHV
      demonstrated that New Zealand paua were highly resistant to infection by Haliotid
      herpesvirus 1 and were fully resistant to the disease AVG.

PMID- 28431887
TI  - Mature cystic teratomas of the ovary.

PMID- 28431888
TI  - A subset of fat-predominant angiomyolipomas label for MDM2: a potential
      diagnostic pitfall; comment on Asch-Kendrick et al. 2016.

PMID- 28431889
TI  - Clinicopathological, radiologic, and molecular study of 23 combined
      hepatocellular-cholangiocarcinomas with stem cell features, cholangiolocellular
      type.
AB  - Cholangiolocellular carcinoma is a type of intrahepatic cholangiocarcinoma (ICC).
      According to the 2010 World Health Organization classification, this carcinoma is
      a combined hepatocellular-cholangiocarcinoma with stem cell features,
      cholangiolocellular type (CHC-SC-CLC). The aim of this study was to compare the
      clinicopathological characteristics of CHC-SC-CLC and conventional ICC. Based on
      the gross and histologic characteristics, we divided consecutive ICC tumors into
      CHC-SC-CLC (n = 23), mass-forming (MF; n = 57), and non-MF (n = 22) groups.
      Compared with MF and non-MF groups, the CHC-SC-CLC group featured history of
      hepatolithiasis or bile duct operation in significantly fewer patients (4.3%
      versus 14.8% and 86.4%, respectively; P < .001) and was more common in the right
      lobe (70% versus 47% and 27%; P = .033) but lower frequency of invasive growth or
      peritumoral Glisson sheath invasion (61% and 22% versus 77% and 33% and 100% and
      86%, respectively; P = .002 and P < .001) and absence of mucous production (0
      versus 77% and 96%; P < .001). In CHC-SC-CLCs, the mutation rate of isocitrate
      dehydrogenase 1 (IDH1) or IDH2 was significantly higher (35%) than in MF (4%) or
      non-MF (0) ICCs (P < .001). The 1-, 3-, and 5-year postresection survival rates
      were also significantly better with CHC-SC-CLCs (93%, 79%, and 52%, respectively)
      than with MF (72%, 46%, and 40%) or non-MF (61%, 18%, and 0) ICCs (P = .041).
      Thus, CHC-SC-CLC tumors demonstrated an indolent growth pattern, more frequent
      IDH1/2 gene mutations, and better prognosis than did MF or non-MF ICC tumors.

PMID- 28431890
TI  - Which facilitates the evolution of cooperation more, retaliation or persistence?
AB  - The existence of cooperation in this world is a mysterious phenomenon. One of the
      mechanisms that explain the evolution of cooperation is repeated interaction. If
      interactions between the same individuals repeat and individuals cooperate
      conditionally, cooperation can evolve. A previous study pointed out that if
      individuals have persistence (i.e., imitate its "own" behavior in the last move),
      cooperation can evolve. However, retaliation and persistence are not mutually
      exclusive decisions, but rather a trade-off in the decision making process of
      individuals. Players can refer to the opponent's behavior and if the actor and
      the opponent opted for the different alternative in the last move, conditional
      cooperators have to give up either retaliation or persistence. The previous study
      also investigated this, and has revealed that the individual should give more
      importance to retaliation than to persistence. However, this study has assumed
      that the errors in perception are absent. In this world, errors in perception are
      present, and trying to imitate the opponent player can sometimes end in failure.
      And, it might be that imitating the focal player, which definitely ends in
      success, is more beneficial than trying to imitate the opponent player, which can
      end in failure especially when the error rate in recognition is large. Here, this
      paper uses evolutionarily stable strategy (ESS) analysis and analyzes the
      stability for reactive strategies against the invasion by unconditional defectors
      in the iterated prisoner's dilemma game. And our analysis reveals that even if we
      take errors in perception into consideration, retaliation facilitates the
      evolution of cooperation more than persistence unexpectedly. In addition, we
      analyze the stability for reactive cooperators against the invasion by a strategy
      other than unconditional defectors. Moreover, we also analyze the deterministic
      model in which unconditional cooperators, unconditional defectors, and the
      reactive strategy at the same time.

PMID- 28431891
TI  - [Vulvovaginal candidiasis: An old disease with new challenges].
AB  - Vulvovaginal candidiasis is an old disease that, even in a modern world,
      continues to have a high incidence. Despite the therapeutic advances, treatments
      are not always effective, and our understanding of the pathogenesis of this
      fungal infection is still incomplete. A discussion is presented in this article
      on the most significant developments related to the fungal virulence factors, the
      role of the immunological mechanisms involved in the vaginal protection, and the
      genetic alterations that confer susceptibility to the recurrent form of this
      mycosis. Current treatments, the use of new agents with antifungal activity, as
      well as the development of strategies, such as vaccination, are approached in the
      context of the complex scenario that governs the interactions between Candida and
      its host.

PMID- 28431892
TI  - A humanized HLA-DR4 mouse model for autoimmune myocarditis.
AB  - Myocarditis, the principal cause of dilated cardiomyopathy and heart failure in
      young adults, is associated with autoimmunity to human cardiac alpha-myosin
      (hCAM) and the DR4 allele of human major histocompatibility II (MHCII). We
      developed an hCAM-induced myocarditis model in human HLA-DR4 transgenic mice that
      lack all mouse MHCII genes, demonstrating that immunization for 3weeks
      significantly increased splenic T-cell proliferative responses and titres of IgG1
      and IgG2c antibodies, abolished weight gain, provoked cardiac inflammation and
      significantly impaired cardiac output and fractional shortening, by
      echocardiography, compared to adjuvant-injected mice. Neither cardiac dilatation
      nor fibrosis occurred at this time point but prolonging the experiment was
      associated with mortality. Treatment with mixtures of hCAM derived peptides
      predicted to have high affinity for DR4 significantly preserved ejection fraction
      and fractional shortening. Our new humanized mouse model of autoimmune
      cardiomyopathy should be useful to refine hCAM-derived peptide treatment.

PMID- 28431893
TI  - Proficiency testing with uncertainty evaluation for measuring activities per unit
      mass of 134Cs and 137Cs in brown rice in Japan.
AB  - In Japan, we conducted proficiency testing of activity measurement by using high
      purity germanium detectors for 134Cs and 137Cs in brown rice grains. Among 176
      reported results, 86 % (for 134Cs) and 93 % (for 137Cs) of the results satisfied
      |En| ? 1. However, 58 reports for 134Cs and 51 reports for 137Cs had some
      failures in their evaluations of uncertainties. The proficiency testing was
      effective to improve the ability of uncertainty evaluation.

PMID- 28431894
TI  - Molecular cloning and functional characterization of duck nucleotide-binding
      oligomerization domain 1 (NOD1).
AB  - Nucleotide-binding oligomerization domain 1 (NOD1) is an imperative cytoplasmic
      pattern recognition receptor (PRR) and considered as a key member of the NOD-like
      receptor (NLR) family which plays a critical role in innate immunity through
      sensing microbial components derived from bacterial peptidoglycan. In the current
      study, the full-length of duck NOD1 (duNOD1) cDNA from duck embryo fibroblasts
      (DEFs) was cloned. Multiple sequence alignment and phylogenetic analysis
      demonstrated that duNOD1 exhibited a strong evolutionary relationship with
      chicken and rock pigeon NOD1. Tissue-specific expression analysis showed that
      duNOD1 was widely distributed in various organs, with the highest expression
      observed in the liver. Furthermore, duNOD1 overexpression induced NF-kappaB
      activation in DEFs and the CARD domain is crucial for duNOD1-mediated NF-kappaB
      activation. In addition, silencing the duNOD1 decreased the activity of NF-kappaB
      in DEFs stimulated by iE-DAP. Overexpression of duNOD1 significantly increased
      the expression of TNF-alpha, IL-6, and RANTES in DEFs. These findings highlight
      the crucial role of duNOD1 as an intracellular sensor in duck innate immune
      system.

PMID- 28431896
TI  - Pressurized IntraPeritoneal Aerosol Chemotherapy - Practical aspects.
AB  - INTRODUCTION: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has been
      introduced as novel treatment for peritoneal carcinomatosis. Only proper patient
      selection, stringent safety protocol and careful surgery allow for a secure
      procedure. We hereby report the essentials for safe implementation. METHODS: All
      consecutive procedures within 20 months after PIPAC implementation were analyzed
      with regards to practical and surgical aspects. Special emphasis was laid on
      modifications of technique and safety measures during the implementation process
      with systematic use of a dedicated checklist. Further, surgical difficulty was
      documented by use of a visual analogue scale (VAS). RESULTS: 127 PIPAC procedures
      were performed in 58 patients from January 2015 until October 2016. 81% of
      patients had at least one previous laparotomy. Median operation time was 91 min
      (87-103) for the first 20 cases, 93 min (IQR 88-107) for PIPAC21-50, and 103 min
      (IQR 91-121) for the following 77 procedures. Primary and secondary non-access
      occurred in 3 patients (2%), all of them having prior hyperthermic
      intraperitoneal chemotherapy (HIPEC). Using open Hasson technique, one single
      bowel lesion occurred, which was the only intraoperative complication. One 5 mm
      and another 10/12 mm trocar were used in 88% of procedures while additional
      trocars were needed in 12%. No leak of cytostatics was observed and no procedure
      needed to be stopped. VAS for overall difficulty of the procedure was 3 +/- 2.4,
      and 3 +/- 2.9 and 3 +/- 2.5, respectively, for abdominal access and
      intraoperative staging. CONCLUSIONS: With standardized surgical approach and
      dedicated safety checklist, PIPAC can be safely introduced in clinical routine
      with minimal learning curve.

PMID- 28431895
TI  - Hemolymph proteins of Anopheles gambiae larvae infected by Escherichia coli.
AB  - Anopheles gambiae is a major vector of human malaria and its immune system in
      part determines the fate of ingested parasites. Proteins, hemocytes and fat body
      in hemolymph are critical components of this system, mediating both humoral and
      cellular defenses. Here we assessed differences in the hemolymph proteomes of
      water- and E. coli-pricked mosquito larvae by a gel-LC-MS approach. Among the
      1756 proteins identified, 603 contained a signal peptide but accounted for two
      third of the total protein amount on the quantitative basis. The sequence
      homology search indicated that 233 of the 1756 may be related to defense. In
      general, we did not detect substantial differences between the control and
      induced plasma samples in terms of protein numbers or levels. Protein
      distributions in the gel slices suggested post-translational modifications (e.g.
      proteolysis) and formation of serpin-protease complexes and high Mr immune
      complexes. Based on the twenty-five most abundant proteins, we further suggest
      that major functions of the larval hemolymph are storage, transport, and
      immunity. In summary, this study provided first data on constitution, levels, and
      possible functions of hemolymph proteins in the mosquito larvae, reflecting
      complex changes occurring in the fight against E. coli infection.

PMID- 28431897
TI  - Aetiology of renal failure in patients with infective endocarditis. The role of
      antibiotics.
AB  - BACKGROUND AND OBJECTIVES: The possible renal toxicity of certain antibiotics
      (AB) is well known. The objective of our work is to know the possible effect of
      AB treatments in the development of renal failure (RF) in patients with infective
      endocarditis (IE). MATERIAL AND METHOD: Collection from a national multi-centre
      registry of collection on renal function, both prior and its impairment, if any,
      during the treatment of IE and in relation to possible causative factors,
      including the use of AB. RESULTS: Between 2008 and 2012, 1,853 episodes of IE
      reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF.
      They developed new RF or impairment of renal function in 38.7% of the cases. In
      patients with prior RF, impairment was more frequent (64 vs. 31.7%, P<.001).
      Overall, patients with RF were older (70.6 vs. 67 years, P<.01), had more
      comorbidities (Charlson index 5 vs. 4, P<.01), and IE by Staphylococcus aureus
      (32.1 vs. 16.5%, P<.01). Potentially nephrotoxic AB use was only associated with
      RF in patients without prior RF (aminoglycosides: OR=1.47 [95% CI 1.096-1.988],
      P=.010; aminoglycosides with vancomycin: OR=1.49 [95% CI 1.069-2.09], P=.019).
      CONCLUSIONS: In patients without prior RF, the use of nephrotoxic AB is
      associated with impairment of renal function. In patients with RF prior to the IE
      episode, impairment of renal function was more frequent but appears to be more
      related to the severity of infection.

PMID- 28431898
TI  - Serum potassium concentrations: Importance of normokalaemia.
AB  - Abnormalities in potassium concentrations are associated with morbidity and
      mortality. In recent years it has been considered that small variations in serum
      potassium concentrations within normal intervals may also be associated with
      mortality. Strategies for achieving normokalaemia include dietary measures,
      limiting the use of potassium retaining drugs, and use of conventional cation
      exchange resins (calcium/sodium polystyrene sulfonate) and/or the new non
      absorbed cation exchange polymer (patiromer).

PMID- 28431899
TI  - Validation of the FACT-B+4-UL questionnaire and exploration of its predictive
      value in women submitted to surgery for breast cancer.
AB  - INTRODUCTION AND OBJETIVE: The early detection of upper limb complications is
      important in women operated on for breast cancer. The "FACT-B+4-UL"
      questionnaire, a specific variant of the Functional Assessment of Cancer Therapy
      Breast (FACT-B) is available among others to measure the upper limb function.
      PATIENTS AND METHODS: The Spanish version of the upper limb subscale of the FACT
      B+4 was validated in a prospective cohort of 201 women operated on for breast
      cancer (factor analysis, internal consistency, test-retest reliability, construct
      validity and sensitivity to change were determined). Its predictive capacity of
      subsequent lymphoedema and other complications in the upper limb was explored
      using logistic regression. RESULTS: This subscale is unifactorial and has a great
      internal consistency (Cronbach's alpha: 0.87), its test-retest reliability and
      construct validity are strong (intraclass correlation coefficient: 0.986;
      Pearson's R with "Quick DASH": 0.81) as is its sensitivity to change. It didn't
      predict the onset of lymphedema. Its predictive capacity for other upper limb
      complications is low. CONCLUSIONS: FACT-B+4-UL is useful in measuring upper limb
      disability in women surgically treated for breast cancer; but it does not predict
      the onset of lymphoedema and its predictive capacity for others complications in
      the upper limb is low.

PMID- 28431900
TI  - [Quality of initial trauma care in paediatrics].
AB  - INTRODUCTION: Trauma care in Spain is not provided in specific centres, which
      means that health professionals have limited contact to trauma patients. After
      the setting up of a training program in paediatric trauma, the aim of this study
      was to evaluate the quality of the initial care provided to these patients before
      they were admitted to the paediatric intensive care unit (PICU) of a third level
      hospital (trauma centre), as an indirect measurement of the increase in the
      number of health professionals trained in trauma. MATERIAL AND METHODS: Two
      cohorts of PICU admissions were reviewed, the first one during the four years
      immediately before the training courses started (Group 1, period 2001-2004), and
      the second one during the 4 years (Group 2, period 2012-2015) after nearly 500
      professionals were trained. A record was made of the injury mechanism, attending
      professional, Glasgow coma score (GCS), and paediatric trauma score (PTS).
      Initial care quality was assessed using five indicators: use of cervical collar,
      vascular access, orotracheal intubation if GCS <= 8, gastric decompression if
      PTS<=8, and number of actions carried out from the initial four recommended (neck
      control, provide oxygen, get vascular access, provide IV fluids). Compliance was
      compared between the 2 periods. A P<.05 was considered statistically significant.
      RESULTS: A total of 218 patient records were analysed, 105 in Group 1, and 113 in
      Group 2. The groups showed differences both in injury mechanism and in initial
      care team. A shift in injury mechanism pattern was observed, with a decrease in
      car accidents (28% vs 6%; P<.0001). Patients attended to in low complexity
      hospitals increased from 29.4% to 51.9% (P=.008), and their severity decreased
      when assessed using the GCS <= 8 (29.8% vs 13.5%; P=.004), or PTS<=8 (48.5% vs
      29.7%; P=.005). As regards quality indicators, only the use of neck collar
      improved its compliance (17.3% to 32.7%; P=.01). Patients who received no action
      in the initial care remained unchanged (19% vs 11%%; P=.15). CONCLUSIONS:
      Although there are limited improvements, the setting up of a training program has
      not translated into better initial care for trauma patients in our area of
      influence. Trauma training should be complemented with other support measures in
      order to achieve a systematic application of the trauma care principles.

PMID- 28431901
TI  - Clozapine reduces Toll-like receptor 4/NF-kappaB-mediated inflammatory responses
      through inhibition of calcium/calmodulin-dependent Akt activation in microglia.
AB  - Clozapine is an atypical antipsychotic agent used in the treatment of
      schizophrenia and severe mood disorders. Accumulating evidence suggests that
      neuroinflammation is closely associated with the pathogenesis of various
      neurodegenerative diseases and psychiatric disorders. Clozapine exerts anti
      inflammatory activity. However, the molecular mechanism underlying the anti
      inflammatory activity of clozapine is poorly understood. In this study, we found
      that clozapine suppressed lipopolysaccharide (LPS)-induced phosphorylation of
      IkappaBalpha at Ser-32 and of p65/RelA at Ser-468, as well as nuclear factor
      kappa-light-chain-enhancer of activated B cells (NF-kappaB)-dependent
      transcriptional activity in microglial cells. Clozapine downregulated LPS-induced
      Akt phosphorylation at Ser-473. Pharmacological Akt inhibitors ameliorated LPS
      induced NF-kappaB activation. Removal of extracellular Ca2+ by EGTA or
      sequestration of intracellular Ca2+ by BAPTA-AM attenuated LPS-induced Akt
      phosphorylation. Treatment with calmodulin (CaM) antagonists and the CaM kinase
      inhibitor, KN-93, also prevented LPS-induced Akt and NF-kappaB activation,
      suggesting that Ca2+/CaM-dependent Akt activation is critical in LPS-induced NF
      kappaB activation in microglia. These results suggest that clozapine exhibits
      anti-inflammatory activity through the inhibition of Ca2+/CaM/Akt-mediated NF
      kappaB activation.

PMID- 28431902
TI  - Addressing Unmet Maternal Health Needs at a Pediatric Specialty Infant Care
      Clinic.
AB  - OBJECTIVE: The objective of this intervention was to evaluate the feasibility of
      screening mothers of medically fragile infants in the domains of 1) depression,
      2) tobacco exposure, and 3) family planning at a post-neonatal intensive care
      unit (NICU) developmental pediatric visit. Additionally, we sought to estimate
      the percentage who met criteria for further evaluation in the three domains
      assessed. METHODS: A cross-sectional questionnaire was administered to 100
      caregivers of medically fragile infants at a specialty, post-NICU clinic visit.
      Participants' responses in three domains were evaluated and appropriate referrals
      were provided. Analysis was then restricted to the 87 biological mothers who
      completed the screening. Study staff contacted the mothers 2 months later to
      determine whether services had been accessed and to assess overall satisfaction
      with the screening within the pediatric visit. Qualitative interviews were
      conducted with pediatric clinic staff. RESULTS: Screening questionnaires were
      completed by 87 biological mothers. Twenty-two mothers (25%) met referral
      criteria. Pediatric clinic staff and providers were comfortable administering the
      screening instrument, and there was minimal disruption to clinic flow.
      CONCLUSIONS: Mothers of medically fragile infants are likely to have unmet health
      care needs that can be identified at a specialty pediatric clinic visit. A
      screening and referral intervention can be implemented with minimal interruption
      in pediatric clinic flow and is acceptable to mothers and pediatric providers.

PMID- 28431903
TI  - The Effect of Positive Affect on the Memory of Pain.
AB  - The aim of the study was to assess the accuracy of the memory of experimentally
      induced pain and the affect that accompanies experimentally induced pain. Sixty
      two healthy female volunteers participated in the study. In the first phase of
      the study, the participants received three pain stimuli and rated pain intensity,
      pain unpleasantness, state anxiety, and their positive and negative affect. About
      a month later, in the second phase of the study, the participants were asked to
      rate the pain intensity, pain unpleasantness, state anxiety, and the emotions
      they had felt during the first phase of the study. Both recalled pain intensity
      and recalled pain unpleasantness were found to be underestimated. Although the
      positive affect that accompanied pain was remembered accurately, recalled
      negative affect was overestimated and recalled state anxiety was underestimated.
      Experienced pain, recalled state anxiety, and recalled positive affect accounted
      for 44% of the total variance in predicting recalled pain intensity and 61% of
      the total variance in predicting recalled pain unpleasantness. Together with
      recent research findings on the memory of other types of pain, the present study
      supports the idea that pain is accompanied by positive as well as negative
      emotions, and that positive affect influences the memory of pain.

PMID- 28431904
TI  - Self-rated health and mortality with special reference to black-white difference.

PMID- 28431905
TI  - Dynamic interhemispheric competition and vestibulo-cortical control in humans; A
      theoretical proposition.
AB  - Neuroscientific research has made a concerted effort to determine cortical
      localization using various functional imaging techniques. This approach has
      undoubtedly yielded important novel anatomical knowledge, albeit at times
      contradictory, regarding the structural organization of the vestibular cortex.
      Unfortunately however, this knowledge has not translated to our understanding
      regarding how neural mechanisms control vestibular function. Based upon recent
      functional imaging, lesion and neuro-physiological data that have demonstrated
      (i) the close behavioral and neuro-anatomical relationship between cortical
      processing of vestibular and spatial attention signals, and (ii) that inducing
      interhemispheric competition can in-turn strongly modulate vestibular function
      akin to that observed in cortical lesion patients, I herewith propose the
      hypothesis that vestibular cortical processing is controlled, as per for spatial
      attention, via dynamic interhemispheric competition. In the first half of this
      review I discuss previous key findings in the field of vestibular neuroscience
      that can be reinterpreted to support the role of interhemispheric competition for
      the control of high-level vestibular functions. Contrastingly, in the second half
      of this review, I present previous findings that show how disrupting
      interhemispheric interactions can modulate the brainstem-mediated vestibular
      ocular reflex (VOR). I conclude by speculating why interhemispheric competition
      induces correlated biases at the cortical and brainstem level respectively.
      Specifically, I propose that brainstem-mediated vestibulo-spatial and vestibulo
      temporal transformations, in addition to coding for head displacement, underpin a
      generalized cortical magnitude estimation system which the CNS uses to construct
      dynamic spatio-temporal maps of the physical world, in-turn ensuring spatial
      orientation.

PMID- 28431907
TI  - Telomere shortening during aging: Attenuation by antioxidants and anti
      inflammatory agents.
AB  - Telomeres are a repeated sequence -of bases found at the ends of chromosomes. In
      humans, this sequence is TTAGGG, which is repeated over 2000 times. Telomeres
      protect the ends chromosomes from fusion with nearby chromosomes, and allow
      effective replication of DNA. Each time a cell divides, 25-200 base pairs are
      lost from the terminal sequence of chromosomes. By becoming truncated during cell
      division, telomeres protect essential genes from being shortened and thus
      inactivated. In addition, telomeres are sensitive to inflammation and oxidative
      stress, which can further promote telomere shortening. Reduction in the length of
      telomeres leads to the cessation of cell division and thus cellular senescence
      and apoptosis. This review discusses evidence for the role of oxidative stress
      and inflammation in regulating the length of telomeres in mammalian cells during
      senescence. Evidence is presented suggesting that antioxidants and anti
      inflammatories can reduce the pace of shortening of telomere length during aging.
      The distinctive properties of transformed cells suggest that treatment with such
      materials will have a deleterious rather than a protective effect on such
      abnormal cells.

PMID- 28431908
TI  - Implementation of a Person-Centered Medical Care Model in a Skilled Nursing
      Facility: A Pilot Evaluation.
AB  - OBJECTIVES: The objective of this study was to evaluate the feasibility and
      impact of implementing a person-centered medical care model for post-acute care
      residents within a skilled nursing facility (SNF). DESIGN: A mixed-method
      (qualitative and quantitative) pilot evaluation. SETTING: An 89-bed SNF located
      within a large midwestern city. PARTICIPANTS: Forty SNF post-acute patients
      admitted to the facility during a 6-month period were enrolled in the pilot
      evaluation. The patients were 75% women, 57% African American, and had an average
      age of 73. To meet inclusion criteria, patients must have been admitted to the
      facility for rehabilitation with a plan for community discharge, and be
      cognitively able to consent as indicated by a cognitive screening tool or assent
      to participation with family member consent. INTERVENTION: The person-centered
      medical care model included (1) biweekly interdisciplinary care plan meetings,
      scheduled at a time of patients' preference and held in the patient's room; (2)
      patient selection of health-related goals that guide team discussions; (3) use of
      lay-language that facilitated patient understanding; (4) team accountability to
      the patient for patient care preferences; and (5) monthly care-team meetings to
      exchange feedback regarding the team's performance and the model. MEASUREMENT:
      Evaluation data included admission and discharge Patient Activation Measure
      surveys; admission and discharge Care of Chronic Conditions surveys; admission
      and biweekly modified Castle Satisfaction Surveys; admission and discharge
      Patient and Caregiver Engagement surveys; and semistructured interviews with a
      sample of staff, family members, and patients. RESULTS: A significant (P < .01)
      improvement was noted between admission and discharge on both the Care for
      Chronic Conditions and the Patient Activation Measure surveys. Patient
      satisfaction surveys trended toward higher ratings over time on most questions,
      with significant improvement in 2 questions addressing satisfaction with their
      medical provider. Interviews revealed a perception that the model encouraged an
      environment of respect and honesty in patient communications, and an overall
      positive experience. The challenges of scheduling and time were noted by
      respondents. CONCLUSIONS: Implementation of person-centered medical care within
      an SNF was feasible, yet required changing care processes to better address
      individual goals and facilitate communication among patients, providers, and SNF
      staff. Overall pilot results indicated that patients and staff members viewed the
      person-centered care experience positively. Further research is needed to examine
      long-term effects of the model on resident outcomes.

PMID- 28431906
TI  - Transgenic mice with increased astrocyte expression of CCL2 show altered
      behavioral effects of alcohol.
AB  - Emerging research provides strong evidence that activation of CNS glial cells
      occurs in neurological diseases and brain injury and results in elevated
      production of neuroimmune factors. These factors can contribute to
      pathophysiological processes that lead to altered CNS function. Recently, studies
      have also shown that both acute and chronic alcohol consumption can produce
      activation of CNS glial cells and the production of neuroimmune factors,
      particularly the chemokine ligand 2 (CCL2). The consequences of alcohol-induced
      increases in CCL2 levels in the CNS have yet to be fully elucidated. Our studies
      focus on the hypothesis that increased levels of CCL2 in the CNS produce
      neuroadaptive changes that modify the actions of alcohol on the CNS. We utilized
      behavioral testing in transgenic mice that express elevated levels of CCL2 to
      test this hypothesis. The increased level of CCL2 in the transgenic mice involves
      increased astrocyte expression. Transgenic mice and their non-transgenic
      littermate controls were subjected to one of two alcohol exposure paradigms, a
      two-bottle choice alcohol drinking procedure that does not produce alcohol
      dependence or a chronic intermittent alcohol procedure that produces alcohol
      dependence. Several behavioral tests were carried out including the Barnes maze,
      Y-maze, cued and contextual conditioned fear test, light-dark transfer, and
      forced swim test. Comparisons between alcohol naive, non-dependent, and alcohol
      dependent CCL2 transgenic and non-transgenic mice show that elevated levels of
      CCL2 in the CNS interact with alcohol in tests for alcohol drinking, spatial
      learning, and associative learning.

PMID- 28431909
TI  - Antipsychotics and the Risk of Cerebrovascular Accident: A Systematic Review and
      Meta-Analysis of Observational Studies.
AB  - BACKGROUND: Studies investigating the association between antipsychotic use and
      the risk of cerebrovascular accident (CVA) showed inconsistent results. AIM:
      Conduct a systematic review and meta-analysis to evaluate whether use of
      antipsychotics is associated with increased risk of CVA. METHODS: Major
      electronic databases were searched from 1970 to October 2016 for observational
      studies investigating the risk of CVA among users of antipsychotics. Pooled
      estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were obtained
      by random effects meta-analysis. RESULTS: Of 1171 citations identified, 10
      studies were considered eligible. Significant increase in risk of CVA was
      associated with first-generation antipsychotics (OR 1.49; 95% CI 1.24-1.77) but
      not with second-generation antipsychotics (OR 1.31; 95% CI 0.74-2.30). Use of any
      antipsychotics in patients with dementia was associated with a low risk of CVA
      (OR 1.17; 95% CI 1.08-1.26). CONCLUSIONS: The available evidence suggests use of
      with first-generation antipsychotics as opposed to second-generation
      antipsychotics significantly increased the risk of CVA.

PMID- 28431910
TI  - Trends in Geriatrics-Related Translational Research and Funding in the "Big 4"
      Medical Journals.

PMID- 28431911
TI  - Sensor Augmented Insulin Pump Therapy in Older Adults: Impact on Self-Rated
      Health and Glycemic Control.

PMID- 28431912
TI  - Osteosarcopenic Obesity: Prevalence and Relation With Frailty and Physical
      Performance in Middle-Aged and Older Women.
AB  - OBJECTIVES: The aims of this study were to determine the prevalence of
      osteosarcopenic obesity (OSO) and to investigate its association with frailty and
      physical performance in Mexican community-dwelling middle-aged and older women.
      DESIGN: Cross-sectional analysis of a prospective cohort. SETTING: The FraDySMex
      study, a 2-round evaluation of community-dwelling adults from 2 municipalities in
      Mexico City. PARTICIPANTS: Participants were 434 women aged 50 years or older,
      living in the designated area in Mexico City. MEASUREMENTS: Body composition was
      measured with dual-energy X-ray absorptiometry and OSO was defined by the
      coexistence of sarcopenia, osteopenia, or osteoporosis and obesity. Information
      regarding demographic characteristics; comorbidities; mental status; nutritional
      status; and history of falls, fractures, and hospitalization was obtained from
      questionnaires. Objective measurements of muscle strength and function were grip
      strength using a hand dynamometer, 6-meter gait speed using a GAIT Rite
      instrumented walkway, and lower extremity functioning measured by the Short
      Physical Performance Battery (SPPB). Frailty was assessed using the Frailty
      Phenotype (Fried criteria), the Gerontopole Frailty Screening Tool (GFST), and
      the FRAIL scale, to build 3 logistic regression models. RESULTS: The prevalence
      of OSO was 19% (n = 81). Frailty (according to the Frailty Phenotype and the
      GFST) and poor physical performance measured by the SPPB were independently
      associated with OSO, controlled by age. In the logistic regression model
      assessing frailty with the Frailty Phenotype, the odds ratio (95% confidence
      interval) for frailty was 4.86 (2.47-9.55), and for poor physical performance it
      was 2.11 (1.15-3.89). In the model assessing frailty with the GFST, it was 2.12
      (1.10-4.11), and for poor physical performance it was 2.15 (1.18-3.92). Finally,
      in the model with the FRAIL scale, it was 1.69 (0.85-3.36) for frailty and 2.29
      (1.27-4.15) for poor physical performance. CONCLUSION: OSO is a frequent
      condition in middle-aged and older women, and it is independently associated with
      frailty and poor physical performance.

PMID- 28431913
TI  - Use of Medications of Questionable Benefit During the Last Year of Life of Older
      Adults With Dementia.
AB  - OBJECTIVES: To investigate the prevalence and factors associated with the use of
      medications of questionable benefit throughout the final year of life of older
      adults who died with dementia. DESIGN: Register-based, longitudinal cohort study.
      SETTING: Entire Sweden. PARTICIPANTS: All older adults (>=75 years) who died with
      dementia between 2007 and 2013 (n = 120,067). MEASUREMENTS: Exposure to
      medications of questionable benefit was calculated for each of the last 12 months
      before death, based on longitudinal data from the Swedish Prescribed Drug
      Register. RESULTS: The proportion of older adults with dementia who received at
      least 1 medication of questionable benefit decreased from 38.6% 12 months before
      death to 34.7% during the final month before death (P < .001 for trend). Among
      older adults with dementia who used at least 1 medication of questionable benefit
      12 months before death, 74.8% remained exposed until their last month of life.
      Living in an institution was independently associated with a 15% reduction of the
      likelihood to receive >=1 medication of questionable benefit during the last
      month before death (odds ratio 0.85, 95% confidence interval 0.88-0.83).
      Antidementia drugs accounted for one-fifth of the total number of medications of
      questionable benefit. Lipid-lowering agents were used by 8.3% of individuals
      during their final month of life (10.2% of community-dwellers and 6.6% of
      institutionalized people, P < .001). CONCLUSION: Clinicians caring for older
      adults with advanced dementia should be provided with reliable tools to help them
      reduce the burden of medications of questionable benefit near the end of life.

PMID- 28431914
TI  - Pain Trajectories of Nursing Home Residents Nearing Death.
AB  - BACKGROUND/OBJECTIVES: Although examining point in time prevalence of pain among
      nursing home (NH) residents has value, there is a lack of evidence describing the
      actual changes (ie, trajectories) in pain that take place during their last 6
      months of life. The main objective of this study is to describe the major pain
      trajectories experienced by NH residents during their last 6 months of life.
      DESIGN: Secondary analysis of Resident Assessment Instrument-Minimum Data Set
      (MDS) 2.0 data captured as part of the longitudinal Translating Research in Elder
      Care data repository. SETTING: Twenty-seven urban NHs in Western Canada.
      PARTICIPANTS: A total of 962 NH residents who died, had an MDS assessment
      completed within 30 days of death, and resided in a NH for at least 6 months.
      Pain trajectories were stratified by residents who were not severely cognitively
      impaired [Cognitive Performance Scale (CPS) <=3] and those with severe impairment
      (CPS >=4) at death. MEASUREMENTS: MDS-Pain Scale; CPS. RESULTS: In the 6 months
      before death, 60.1% of residents without severe cognitive impairment experienced
      consistently low pain; 34.6% reported experiencing either moderate to severe pain
      or significant increases in pain during this same period of time, and only 5.3%
      experienced any degree of pain improvement. When the trajectories were examined,
      most residents without severe cognitive impairment experienced no to mild pain in
      the time before their death (65.5%); however, we identified a group of residents
      who exhibited a pattern of pain that worsened or remained consistently high right
      until death (38.2%). Although the proportion of residents with "low/mild" pain
      trajectories was statistically greater among those who were severely impaired vs
      those without severe cognitive impairment, across both cognitive impairment
      groups, the general trend in pain trajectories is similar; with about 60% of
      residents experiencing either consistent low or mild pain in their last 6 months
      of life, and about 34% experiencing either substantially high or increasing pain
      levels. CONCLUSIONS: Although a majority of NH residents experienced consistently
      low or improved pain levels in their last 6 months of life, a substantial number
      experienced consistently high or substantially worsening pain levels during this
      same time period. These results highlight the need to better manage pain levels
      for some NH residents during this important period of time.

PMID- 28431915
TI  - Synergistic anticandidal activity of menthol in combination with itraconazole and
      nystatin against clinical Candida glabrata and Candida krusei isolates.
AB  - BACKGROUND: Candida glabrata (C. glabrata) and C. krusei are now emerging as
      serious hospital acquired infections in immunocompromised patients. Menthol, a
      terpenic compound, has been reported to have antifungal activity. OBJECTIVES: The
      aim of this study was to investigate the effect of menthol in combination with
      itraconazole or nystatin against C. glabrata and C. krusei isolates. METHODS: The
      effects of menthol along with itraconazole and nystatin, were evaluated by the
      Clinical Laboratory Standards Institute (CLSI) M44-A and CLSI M27-A3 methods. The
      fractional inhibitory concentration index (FICI) was determined for menthol plus
      itraconazole and nystatin combinations using the checkerboard method. RESULTS:
      The mean of minimum inhibitory concentration (MIC) values of menthol, nystatin
      and itraconazole were 53.2, 2.30 and 1.50 MUg/ml for C. glabrata isolates and
      121, 1.08 and 0.38 MUg/ml for C. krusei isolates, respectively. Menthol in
      combination with itraconazole or nystatin exhibited the synergistic effects
      against all species of Candida tested. FICI values for menthol plus itraconazole
      and nystatin combinations ranged from 0.250 to 0.561 and 0.139 to 0.623 for C.
      glabrata isolates, and 0.182 to 0.750 and 0.188 to 0.760 for C. krusei,
      respectively. CONCLUSIONS: These results support the potential use of menthol as
      an anticandidal agent, and it can be used complementarily with other conventional
      antifungal agents.

PMID- 28431916
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Commentary.

PMID- 28431917
TI  - Effective modification of cell death-inducing intracellular peptides by means of
      a photo-cleavable peptide array-based screening system.
AB  - Intracellular functional peptides that play a significant role inside cells have
      been receiving a lot of attention as regulators of cellular activity. Previously,
      we proposed a novel screening system for intracellular functional peptides; it
      combined a photo-cleavable peptide array system with cell-penetrating peptides
      (CPPs). Various peptides can be delivered into cells and intracellular functions
      of the peptides can be assayed by means of our system. The aim of the present
      study was to demonstrate that the proposed screening system can be used for
      assessing the intracellular activity of peptides. The cell death-inducing peptide
      (LNLISKLF) identified in a mitochondria-targeting domain (MTD) of the Noxa
      protein served as an original peptide sequence for screening of peptides with
      higher activity via modification of the peptide sequence. We obtained 4 peptides
      with higher activity, in which we substituted serine (S) at the fifth position
      with phenylalanine (F), valine (V), tryptophan (W), or tyrosine (Y). During
      analysis of the mechanism of action, the modified peptides induced an increase in
      intracellular calcium concentration, which was caused by the treatment with the
      original peptide. Higher capacity for cell death induction by the modified
      peptides may be caused by increased hydrophobicity or an increased number of
      aromatic residues. Thus, the present work suggests that the intracellular
      activity of peptides can be assessed using the proposed screening system. It
      could be used for identifying intracellular functional peptides with higher
      activity through comprehensive screening.

PMID- 28431918
TI  - Gender dependent effects of fasting blood glucose levels and disease duration on
      biochemical markers in type 2 diabetics: A pilot study.
AB  - AIM: The impact of fasting blood glucose levels (FBG) and disease duration on
      type 2 diabetes in Indian population is still unclear. The present study examines
      gender-dependent effects of FBG and disease duration on lipid profile,
      adipocytokines and related biochemical parameters in diabetic individuals.
      METHODS: Type 2 diabetic individuals (n=100) were classified depending on FBG:
      patients with normal FBG (Glucose<126mg/dl) and patients with high FBG
      (Glucose>=126mg/dl); and disease duration: >=0-<=3yr, >3-<=7yr, >7yr. RESULTS:
      Males with high FBG had significantly higher serum glucose, triglycerides, very
      low density lipoprotein (VLDL), serum glutamic oxaloacetic transaminase (SGOT),
      serum glutamic pyruvic transaminase (SGPT) and waist hip ratio (WHR) than males
      with normal FBG. Females with high FBG had significant increase in serum glucose,
      adiponectin and creatinine while decrease in leptin levels than females with
      normal FBG. Males with high FBG had higher WHR, superoxide dismutase, SGOT, SGPT
      and lower adiponectin, leptin than females with high FBG. Significant positive
      association was observed between glucose and cholesterol, triglyceride, VLDL and
      urea in males with high FBG. With chronic diabetes for >7yr, males had increased
      systolic blood pressure, glucose, LDL, urea and low catalase activity as compared
      to other disease duration groups. However, females had higher adiponectin,
      creatinine and lower body mass index and cholesterol. CONCLUSIONS: High FBG in
      males adversely affects lipid profile, adipocytokines and liver function. Some of
      these effects exacerbate as disease progresses. Higher adiponectin may have
      desirable effects on metabolic markers in females.

PMID- 28431919
TI  - Influence of scaffold design on host immune and stem cell responses.
AB  - The combined culture of isolated stem cells in tissue engineering scaffolds
      represents a popular strategy for the regeneration of specialized tissues.
      Despite of improved outcomes in some tissues, this stem cell-seeded tissue
      engineering strategy has not led to significant tissue regeneration as expected.
      The lower-than-expected outcome may be caused by overwhelming immune responses to
      scaffold materials and poor survival of seeded stem cells following implantation.
      This review is aimed at summarizing the success and failure of this strategy and
      also shedding some light on new directions to design scaffolds for promoting
      regenerative responses via autologous stem cells. The first half of this review
      summarizes the influence of scaffold physical and chemical properties on immune
      cell responses to scaffold implants. The second half focuses on the influence of
      scaffold design to alter immune and stem cell responses for achieving desirable
      tissue regeneration.

PMID- 28431920
TI  - The microbiome in anti-cancer therapy.
AB  - The commensal microbiome constitutes an important modulator of host physiology
      and risk of disease, including cancer development and progression. Lately, the
      microbiome has been suggested to modulate the efficacy of anti-cancer treatment.
      Examples include chemotherapy and total body irradiation-induced barrier function
      disruption, leading to microbial efflux that drives activation of anti
      tumorigenic T cells; Microbiome-driven release of reactive oxygen species
      contributing to the efficacy of platinum salts; and microbiome-induced immune
      priming promoting the anti-tumor effects of alkylating chemotherapy and immune
      checkpoint inhibitors. Furthermore, selected commensals are able to colonize
      solid tumors. This 'tumor microbiome' may further impact local tumor responses to
      treatment and potentially be harnessed for tumor-specific targeting and
      therapeutic delivery. In this review, we present recent advances in understanding
      of the intricate role of microbiome in modulating efficacy of a number of anti
      cancer treatments, and discuss how anti-cancer treatment approaches utilizing the
      tumor microbiome may enhance oncological treatment efficacy.

PMID- 28431921
TI  - Optimization of the Helmintex method for schistosomiasis diagnosis.
AB  - A diagnostic test that is reliable, sensitive, and applicable in the field is
      extremely important in epidemiological surveys, during medical treatment for
      schistosomiasis, and for the control and elimination of schistosomiasis. The
      Helmintex (HTX) method is based on the use of magnetic beads to trap eggs in a
      magnetic field. This technique is highly sensitive, but the screening of fecal
      samples consumes lots of time, thus delaying the results, especially in field
      studies. The objective of this work was to determine the effects of incorporation
      of the detergent Tween-20 into the method in an attempt to decrease the final
      pellet volume produced by the HTX method as well as the use of ninhydrin to stain
      the Schistosoma mansoni eggs. We showed that these modifications reduced the
      final volume of the fecal sediment produced in the last step of the HTX method by
      up to 69% and decreased the screening time to an average of 10.1 min per sample.
      The use of Tween 20 and ninhydrin led to a high percentage of egg recovery
      (27.2%). The data obtained herein demonstrate that the addition of detergent and
      the use of ninhydrin to the HTX process can optimize the screening step and also
      improve egg recovery, thus justifying the insertion of these steps into the HTX
      method.

PMID- 28431922
TI  - Microvascular injury and the kidney in hypertension.
AB  - Renal macrocirculation participates in the development of arterial hypertension.
      The elevation in systemic blood pressure (BP) can damage the kidney starting in
      the microcirculation. Established arterial hypertension impinge upon the large
      arteries and stiffness develops. As a consequence central BP raises and BP
      pulsatility appear and contribute to further damage renal microcirculation by
      direct transmission of the elevated BP.

PMID- 28431924
TI  - Racial disparities in HIV.

PMID- 28431923
TI  - Sources of racial disparities in HIV prevalence in men who have sex with men in
      Atlanta, GA, USA: a modelling study.
AB  - BACKGROUND: In the USA, men who have sex men (MSM) are at high risk for HIV, and
      black MSM have a substantially higher prevalence of infection than white MSM. We
      created a simulation model to assess the strength of existing hypotheses and data
      that account for these disparities. METHODS: We built a dynamic, stochastic,
      agent-based network model of black and white MSM aged 18-39 years in Atlanta, GA,
      USA, that incorporated race-specific individual and dyadic-level prevention and
      risk behaviours, network attributes, and care patterns. We estimated parameters
      from two Atlanta-based studies in this population (n=1117), supplemented by other
      published work. We modelled the ability for racial assortativity to generate or
      sustain disparities in the prevalence of HIV infection, alone or in conjunction
      with scenarios of observed racial patterns in behavioural, care, and
      susceptibility parameters. FINDINGS: Race-assortative mixing alone could not
      sustain a pre-existing disparity in prevalence of HIV between black and white
      MSM. Differences in care cascade, stigma-related behaviours, and CCR5 genotype
      each contributed substantially to the disparity (explaining 10.0%, 12.7%, and
      19.1% of the disparity, respectively), but nearly half (44.5%) could not be
      explained by the factors investigated. A scenario assessing race-specific
      reporting differences in risk behaviour was the only one to yield a prevalence in
      black MSM (44.1%) similar to that observed (43.4%). INTERPRETATION: Racial
      assortativity is an inadequate explanation for observed disparities. Work to
      close the gap in the care cascade by race is imperative, as are efforts to
      increase serodiscussion and strengthen relationships among black MSM
      particularly. Further work is urgently needed to identify other sources of, and
      pathways for, this disparity, to integrate concomitant epidemics into models, and
      to understand reasons for racial differences in behavioural reporting. FUNDING:
      The Eunice Kennedy Shriver National Institute of Child Health and Development,
      the National Institute of Allergy and Infectious Diseases, the National Institute
      of Minority Health and Health Disparities, and the National Institute of Mental
      Health.

PMID- 28431925
TI  - Analysis of PM2.5-induced cytotoxicity in human HaCaT cells based on a
      microfluidic system.
AB  - Human exposure to PM2.5 causes several adverse health effects. Skin is the first
      barrier against harmful environmental substances and can directly contact with
      PM2.5, but there is no study about PM2.5-induced cytotoxicity in human skin cells
      on the molecular level partially due to the shortcomings of traditional research
      methods. In present study, we established a microfluidic system including a cell
      culture chip integrated with a high-throughput protein microarray chip to
      investigate the mechanism of PM2.5-mediated cytotoxicity in human HaCaT cells. We
      found that PM2.5 was lodged inside the cytoplasm, mitochondria and nucleus of
      HaCaT cells by TEM. Flow cytometry analysis indicated that the cell apoptosis
      rate increased from 0.49% to 53.4%. The results of protein microarray showed that
      NF-kappaB and NALP3 signal transductions were activated in HaCaT cells after
      PM2.5 stimulations, up-regulating the expression of IL-1beta and IL-6, which
      resulted in inflammatory response in HaCaT cells. Our findings provide a
      molecular insight into PM2.5-induced skin injury.

PMID- 28431926
TI  - Multiple repair pathways mediate cellular tolerance to resveratrol-induced DNA
      damage.
AB  - Resveratrol (RSV) has been reported to exert health benefits for the prevention
      and treatment of many diseases, including cancer. The anticancer mechanisms of
      RSV seem to be complex and may be associated with genotoxic potential. To better
      understand the genotoxic mechanisms, we used wild-type (WT) and a panel of
      isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects
      and molecular mechanisms of cellular tolerance to RSV. Our results showed that
      RSV induced significant formation of gamma-H2AX foci and chromosome aberrations
      (CAs) in WT cells, suggesting direct DNA damage effects. Comparing the survival
      of WT with isogenic DNA-repair deficient DT40 cell lines demonstrated that single
      strand break repair (SSBR) deficient cell lines of Parp1-/-, base excision repair
      (BER) deficient cell lines of Polbeta-/-, homologous recombination (HR) mutants
      of Brca1-/- and Brca2-/- and translesion DNA synthesis (TLS) mutants of Rev3-/-
      and Rad18-/- were more sensitive to RSV. The sensitivities of cells were
      associated with enhanced DNA damage comparing the accumulation of gamma-H2AX foci
      and number of CAs of isogenic DNA-repair deficient DT40 cell lines with WT cells.
      These results clearly demonstrated that RSV-induced DNA damage in DT40 cells, and
      multiple repair pathways including BER, SSBR, HR and TLS, play critical roles in
      response to RSV- induced genotoxicity.

PMID- 28431927
TI  - Membrane insertion of F0 c subunit of F0F1 ATPase depends on glycolipozyme MPIase
      and is stimulated by YidC.
AB  - The F0 c subunit of F0F1 ATPase (F0-c) possesses two membrane-spanning stretches
      with N- and C-termini exposed to the periplasmic (extracellular) side of the
      cytoplasmic membrane of E. coli. Although F0-c insertion has been extensively
      analyzed in vitro by means of protease protection assaying, it is unclear whether
      such assays allow elucidation of the insertion process faithfully, since the
      membrane-protected fragment, an index of membrane insertion, is a full-length
      polypeptide of F0-c, which is the same as the protease-resistant conformation
      without membrane insertion. We found that the protease-resistant conformation
      could be discriminated from membrane-insertion by including octyl glucoside on
      protease digestion. By means of this system, we found that F0-c insertion depends
      on MPIase, a glycolipozyme involved in membrane insertion, and is stimulated by
      YidC. In addition, we found that acidic phospholipids PG and CL transform F0-c
      into a protease-resistant form, while MPIase prevents the acquisition of such a
      protease-resistant conformation.

PMID- 28431928
TI  - Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small
      cell lung cancer cell viability and xenograft tumor growth.
AB  - Lung cancer is the leading cause of cancer death worldwide. Small-cell lung
      cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year
      survival rate below 10%. Although chemotherapy using cisplatin has been proven
      effective in SCLC treatment, conventional dose of cisplatin causes adverse side
      effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is
      increasingly used alone or in combination with other therapeutics in cancer
      treatment. Herein, we aimed to address whether low dose cisplatin combination
      with PDT can effectively induce SCLC cell death by using in vitro cultured human
      SCLC NCI-H446 cells and in vivo tumor xenograft model. We found that both
      cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells.
      Importantly, co-treatment with low dose cisplatin (1 MUM) and PDT (1.25 J/cm2)
      synergistically inhibited cell viability and cell migration. We further showed
      that the combined therapy induced a higher level of intracellular ROS in cultured
      NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was
      recapitulated in tumor xenograft as revealed by a more robust increase in the
      staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken
      together, our findings suggest that low dose cisplatin combination with PDT can
      be an effective therapeutic modality in the treatment of SCLC patients.

PMID- 28431929
TI  - Effects of naturally occurring charged mutations on the structure, stability, and
      binding of the Pin1 WW domain.
AB  - Pin1 is a peptidyl-prolyl cis-trans isomerase, whose WW domain specifically
      recognizes the pSer/Thr-Pro motif. Pin1 is involved in multiple phosphorylation
      events that regulate the activities of various substrates, and Pin1 deregulation
      has been reported in various diseases, including cancer and Alzheimer's disease.
      The WW domain of Pin1 has been used as a small model protein to investigate the
      folding mechanisms of the beta-sheet structure by studying the effect of
      mutations or its naturally occurring variants. However, only a few studies have
      investigated the structure and binding of Pin1 WW mutants. In the present work,
      two naturally occurring Pin1 WW variants, namely, G20D and S16R, derived from the
      cynomolgus monkey and African green monkey, respectively, were selected to
      investigate the influence of charge mutation on the structure, stability, and
      binding properties of the Pin1 WW domain. Analysis using a combination of nuclear
      magnetic resonance (NMR) and chemical shift-based calculations revealed that the
      G20D and S16R mutants had high structural similarity to the wild-type Pin1 WW
      domain. However, the presence of a charge mutation significantly decreased the
      stability of the Pin1 WW domain. Both the wild-type and G20D forms of the Pin1 WW
      domain utilized a three-site mode to bind to a phosphorylated Tau peptide, pT231,
      whereas the S16R mutant binds to the pT231 peptide either in a non-specific
      manner or through a totally different binding mechanism. Correspondingly, the
      wild-type and two mutant Pin1 WW domains showed different binding affinities to
      the Tau phosphopeptide. Considering that the WW domain participates in the
      catalytic activity of the Pin1 isomerase, our study represents a novel approach
      for studying Pin1 function through the analysis of its naturally occurring
      mutants.

PMID- 28431930
TI  - Quantitative proteomics reveals key proteins regulated by eicosapentaenoic acid
      in endothelial activation.
AB  - Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid (PUFA), has been
      shown to decrease the risk of atherosclerosis by attenuating endothelial
      activation. In this study, we used mass spectrometry-based label-free
      quantitative proteomics to study the protective mechanisms of EPA and to identify
      key proteins that regulated by EPA in endothelial activation. Arachidonic acid
      (AA) was used as a control. HUVECs were pretreated with each of the two PUFAs,
      and then stimulated with TNFalpha as a model of endothelial activation. A total
      of 3391 proteins were identified, and 1958 proteins were quantified. Pearson's
      correlation coefficients revealed the excellent biological reproducibility of the
      proteomic results. Gene Ontology and KEGG enrichment analysis of differentially
      expressed proteins was performed, thus leading to the identification of the
      glutathione metabolism, oxidation reduction, and DNA replication as the most
      significantly enriched pathways. Seven key proteins were identified: elongation
      factor Tu (mitochondrial, TUFM), integrin alpha 6 (ITGA6), catalase (CAT),
      annexin A6 (ANXA6), heat shock 70 kDa protein 1A (HSPA1A), glutamate-cysteine
      ligase regulatory subunit (GCLM), and heme oxygenase 1 (HMOX1). Further
      connections among these proteins were also revealed by protein-protein
      interaction analysis. The mRNA levels of CAT, GCLM, and HMOX1 were verified with
      real-time PCR. The protein level of CAT was verified using Western blotting. This
      study is an in-depth proteomics analysis of EPA-treated cells and may provide
      possible insights into the molecular mechanisms of EPA's cytoprotective and
      atheroprotective effects.

PMID- 28431931
TI  - Peroxiredoxin 5 promotes the epithelial-mesenchymal transition in colon cancer.
AB  - Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The
      high mortality rate of patients with colon cancer is due to cancer cell invasion
      and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is
      essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be
      overexpressed in various tumor tissues, and involved to be responsible for tumor
      progression. However, the exact role of PRX5 in colon cancer remains to be
      investigated enhancing proliferation and promoting EMT properties. In this study,
      we constructed stably overexpressing PRX5 and suppressed PRX5 expression in CRC
      cells. Our results revealed that PRX5 overexpression significantly enhanced CRC
      cell proliferation, migration, and invasion. On the other hand, PRX5 suppression
      markedly inhibited these EMT properties. PRX5 was also demonstrated to regulate
      the expression of two hallmark EMT proteins, E-cadherin and Vimentin, and the EMT
      inducing transcription factors, Snail and Slug. Moreover, in the xenograft mouse
      model, showed that PRX5 overexpression enhances tumor growth of CRC cells. Thus,
      our findings first provide evidence in CRC that PRX5 promotes EMT properties by
      inducing the expression of EMT-inducing transcription factors. Therefore, PRX5
      can be used as a predictive biomarker and serves as a putative therapeutic target
      for the development of clinical treatments for human CRC.

PMID- 28431932
TI  - The LncRNA ZBED3-AS1 induces chondrogenesis of human synovial fluid mesenchymal
      stem cells.
AB  - Human synovial fluid-derived mesenchymal stem cells (SFMSCs) have great potential
      for cartilage induction and are promising for cell-based strategies for articular
      cartilage repair. Many long non-coding RNAs (lncRNAs) regulate chondrogenesis of
      MSCs. We hypothesized that the divergent lncRNA ZBED3-AS1, which binds locally to
      chromatin, could promote the expression of zbed3, a novel Axin-interacting
      protein that activates Wnt/beta-catenin signaling, involved in chondrogenesis.
      However, the function of ZBED3-AS1 in SFMSCs is unclear. In this study, the
      expression, biological function, and roles of ZBED3-AS1 in SFMSC chondrogenesis
      were examined by multilineage differentiation, flow cytometry, and gain-of
      function studies. We found that ZBED3-AS1 promotes chondrogenesis. Furthermore,
      ZBED3-AS1 could directly increase zbed3 expression. Finally, the wnt-inhibitor
      DKK1 could reverse the stimulatory effect of ZBED3-AS1 on chondrogenesis. These
      findings demonstrate the role of a new lncRNA, ZBED3-AS1, in SFMSC chondrogenesis
      and may improve osteoarthritis treatment.

PMID- 28431933
TI  - Caspofungin versus micafungin in the incidence of hepatotoxicity in patients with
      normal to moderate liver failure.
AB  - BACKGROUND: One of the major adverse events of caspofungin and micafungin is
      hepatotoxicity, however, there are few reports compared the incidence of
      hepatotoxicity between caspofungin and micafungin. Herein, the primary objective
      of this study was to compare the incidence of hepatotoxicity between caspofungin
      and micafungin treatments for patients with fungal or suspected fungal infection.
      METHODS: In total, 201 patients [caspofungin group: 66 patients; micafungin
      group: 135 patients] treated with echinocandins from April 2014 to November 2015
      at Aichi Medical University Hospital. Investigation item were as follows; sex,
      age, weight, height, duration of treatment, total dose, disease type, clinical
      isolates, liver enzyme levels, concomitant medications. Liver function was
      assessed in accordance with Common Terminology Criteria for Adverse Events
      (CTCAE) Version 4.0. We divided into two groups depend on their liver enzyme
      levels before treated with echinocandins; normal group (liver enzyme levels <=
      CTCAE Grade 1), abnormal group (liver enzyme levels >= CTCAE Grade 2). RESULTS:
      The overall incidence of serious hepatotoxicity (Grade 3 or higher) was 6.1%
      (4/66) in the caspofungin group and 7.4% (10/135) in the micafungin group. The
      proportion of patients used caspofungin and micafungin showed serious
      hepatotoxicity were 0% (0/47) and 6.5% (7/108) in normal group (p = 0.17), and
      21.1% (4/19) and 10.7% (3/28) in abnormal group (p = 0.42). CONCLUSION: There was
      no notable difference in serious hepatotoxicity between the caspofungin group and
      the micafungin group, even though in patients with abnormal liver enzyme levels
      (CTCAE grade 2 or higher).

PMID- 28431934
TI  - Etiological analysis and epidemiological comparison among adult CAP and NHCAP
      patients in Okinawa, Japan.
AB  - BACKGROUND: Etiological epidemiology and diagnosis are important issues for CAP
      and NHCAP. Despite the availability of effective therapies, significant morbidity
      and mortality ensues. METHODS: We retrospectively analyzed the etiology of 200
      pneumonia patients at the University of the Ryukyus Hospital. Patients were
      categorized into CAP (n = 97) or NHCAP (n = 103), according to the Japanese
      Respiratory Society guidelines. Diagnoses were made using clinical tests
      including, Gram stain, bacterial culture, serum and urinary tests. RESULTS:
      Pathogens were detected in 71% of patients, and identified as the source of
      infection in 52% (104/200). The majority of patients suffered from Streptococcus
      pneumoniae (32/200), Haemophilus influenzae (22/200), and Moraxella catarrhalis
      (16/200). Gram stain guided pathogen-oriented therapy decisions for 38 of 96
      patients with unknown pathogens. Atypical pathogens were only diagnosed in CAP
      patients (n = 5). Severity of pneumonia was related to male sex (p = 0.006), and
      preexisting conditions, such as chronic heart failure (p < 0.001) and COPD (p <
      0.001). Risk factors associated with increased length of stay included chronic
      heart failure, chronic renal failure, other pulmonary diseases and diabetes.
      Mortality for NHCAP patients was associated with lung cancer and bronchiectasis.
      CAP patients were more frequently admitted during winter months, while NHCAP
      patients were admitted during all other seasons. Seasonal patterns for individual
      pathogens could not be determined. CONCLUSION: Gram staining remains useful to
      guiding diagnostics. Pathogens affecting CAP and NHCAP patients were not
      significantly different; as such, attention should be focused on the management
      of underlying conditions. Clinical outcomes were not affected by guideline
      discordant therapy.

PMID- 28431935
TI  - Diversity changes of microbial communities into hospital surface environments.
AB  - Previous works have demonstrated considerable variability in hospital cleanliness
      in Japan, suggesting that contamination is driven by factors that are currently
      poorly controlled. We undertook 16S rRNA sequence analysis to study population
      structures of hospital environmental microbiomes to see which factor(s) impacted
      contamination. One hundred forty-four samples were collected from surfaces of
      three hospitals with distinct sizes ("A": >500 beds, "B": 100-500 beds, "C": <100
      beds). Sample locations of two ward types (Surgical and Internal) included
      patient room bed table (multiple) (4BT), patient overbed table (multiple) (4OT),
      patient room sink (multiple) (4S), patient room bed table (single) (SBT), patient
      overbed table (single) (SOT), patient room sink (single) (SS), nurse desk (ND),
      and nurse wagon (NW). Total DNA was extracted from each sample, and the 50
      samples that yielded sufficient DNA were used for further 16S rRNA sequencing of
      hospital microbiome populations with cluster analysis. The number of assigned
      bacterial OTU populations was significantly decreased in hospital "C" compared to
      the other hospitals. Cluster analysis of sampling locations revealed that the
      population structure in almost all locations of hospital "C" and some locations
      in the other hospitals was very similar and unusually skewed with a family,
      Enterobacteriaceae. Interestingly, locations included patient area (4OT, 4BT,
      SBT) and nurse area (ND), with a device (NW) bridging the two and a place (4S and
      SS) shared between patients or visitors. We demonstrated diversity changes of
      hospital environmental microbiomes with a skewed population, presumably by
      medical staff pushing NWs or sinks shared by patients or visitors.

PMID- 28431936
TI  - Galectin-3 mediates the pulmonary arterial hypertension-induced right ventricular
      remodeling through interacting with NADPH oxidase 4.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disorder that affects both
      pulmonary vasculature and the heart. The response of the right ventricle (RV) to
      the increased afterload is an important determinant of the PAH final outcome.
      Galectin-3 (Gal-3), a novel biomarker in left cardiac remodeling, takes part in
      multiple pathophysiological processes including the inflammation, fibrosis,
      immunity, and oxidative stress. The levels of Gal-3 are elevated in PAH patients,
      although the exact mechanisms underlie the PAH-induced right ventricular
      structural changes remain unclear. Our results showed that the serum Gal-3 and
      NADPH oxidase 4 (Nox4) levels were significantly elevated and correlated in 26
      human PAH patients when compared with 14 age- and sex-matched healthy controls.
      In the monocrotaline-induced PAH rat models of right ventricular hypertrophy and
      fibrosis, the Gal-3 and Nox4 expressions were both significantly upregulated
      compared with the controls. Moreover, the Gal-3 positive areas were co-localized
      with the collagen III-specific staining and the Gal-3 and Nox4 were partly co
      localized in the intercellular area. The exogenous Gal-3 recombinant protein
      stimulated the proliferation, differentiation, collagen deposition, and Nox4
      expression of cardiac fibroblasts. These simulations were blocked by the Gal-3
      knockdown. The profibrotic effects of transforming growth factor-beta1 (TGF
      beta1) on the cardiac fibroblasts were partially mediated by the Gal-3.
      Subsequently, our results showed that Gal-3 mediated the TGF-beta1-induced
      cardiac fibrotic process through interacting with the Nox4 and Nox4-derived
      oxidative stress. Therefore, Gal-3 plays an important role in the PAH-induced
      right ventricular remodeling through interacting with the Nox4 and Nox4-derived
      oxidative stress. Gal-3 may become a RV-specific diagnostic and therapeutic
      target for clinics.

PMID- 28431937
TI  - Structural modifications in the sugar moiety as a key to improving the anticancer
      effectiveness of doxorubicin.
AB  - Doxorubicin (DOX) is one of the most commonly used and effective chemotherapeutic
      agents. Despite its clinical benefits, the use of DOX is often limited by serious
      adverse effects, such as severe cardiotoxicity and myelosuppression. Recent
      progress in chemical synthesis has enabled the design of modified anthracyclines
      with a sugar moiety being a desirable subject of research. A series of new
      analogues of DOX has been synthesised, in which the amino group in the
      daunosamine moiety was replaced by a formamidine system containing the rest of
      the cyclic secondary amine with gradually increased ring size. An additional
      product containing the oxazoline ring in daunosamine moiety was obtained during
      the synthesis of formamidinodoxorubicin from DOX. Formamidine derivatives
      demonstrate better anticancer properties when compared with parental DOX, such as
      lower cardiotoxicity and comparable or higher antiproliferative activity. Also
      the analogue containing the oxazoline ring in the structure shows promising
      results. Structural modifications in the sugar moiety, involving oxazoline ring
      formation, increase the anticancer activity in terms of apoptosis induction and
      genotoxicity. It can be concluded that chemical modification at the C3' position
      is a good method to increase the activity against cancer cells in vitro.

PMID- 28431938
TI  - Selective inhibition of EZH2 by a small molecule inhibitor regulates microglial
      gene expression essential for inflammation.
AB  - Multiple studies have documented that Enhancer of zeste homolog 2 (EZH2) could
      play a role in inflammation and a wide range of malignancies; however, the
      underlying mechanisms remain largely unaddressed. Microglial activation is a key
      process in the production and release of numerous pro-inflammatory mediators that
      play important roles in inflammation and neurodegeneration in the central nervous
      system (CNS). Therefore, our aim was to investigate whether inhibition of EZH2
      with the selective small molecule inhibitor EPZ-6438 protects against neonatal
      microglial activation. First, in mouse primary microglial cells and a microglial
      cell line, we found that LPS can rapidly increase EZH2 mRNA level and we
      subsequently performed gene expression profiling and constructed networks in
      resting, EPZ-6438-treated, LPS-treated and LPS+EPZ-6438-treated primary
      microglial cells and a microglial cell line using transcriptome RNA sequencing
      and bioinformatics analyses. By examining the RNA sequencing, we identified EPZ
      6438 target genes and co-regulated modules that were critical for inflammation.
      We also identified unexpected relationships between the inducible transcription
      factors (TFs), motif strength, and the transcription of key inflammatory
      mediators. Furthermore, we showed that EPZ-6438 controls important inflammatory
      gene targets by modulating interferon regulatory factor (IRF) 1, IRF8, and signal
      transducer and activator of transcription (STAT) 1 levels at their promoter
      sites. Our unprecedented findings demonstrate that pharmacological interventions
      built upon EZH2 inhibition by EPZ-6438 could be a useful therapeutic approach for
      the treatment of neuroinflammatory diseases associated with microglial
      activation.

PMID- 28431939
TI  - Modulation of HAT activity by the BRCA2 N372H variation is a novel mechanism of
      paclitaxel resistance in breast cancer cell lines.
AB  - Paclitaxel stabilizes microtubule polymerization, enhances microtubule assembly,
      and G2/M arrests, leading to cell death. Paclitaxel resistance has been
      attributed to a variety of mechanisms. In the present study, we define a new
      resistance mechanism to paclitaxel based on BRCA2 variation. Chemo-sensitivity to
      paclitaxel based on the variations was compared. Restoration of paclitaxel
      sensitivity was induced indirectly with combined treatment of paclitaxel and HDAC
      inhibitor. Variant and wild type of BRCA2 clones were obtained from wild and
      variant cells, respectively. Chemo-sensitivity, P/CAF and BubR1 expression and
      acetylation, BRCA2-P/CAF and BRCA2-BubR1 interactions, and HAT activities of the
      clones with BRCA2 variation were compared. We identified an association between
      chemo-sensitivity and BRCA2 N372H variation. The IC50 of paclitaxel in
      heterozygous variation was higher than that of wild type. There were no
      differences in basic expression levels of BRCA2 among variant types. However,
      P/CAF expression, of BRCA2-P/CAF interaction, and HAT activity were significantly
      lower in heterozygous variants than in the wild type. After HDAC inhibitor
      treatment, HAT activity and paclitaxel sensitivity were restored in variant
      cells. Cell lines transformed from wild to variant or from variant to wild showed
      reciprocal changes in P/CAF expression, BRCA2-P/CAF interaction, HAT activity,
      and paclitaxel sensitivity. Forced expression of the BRCA2 heterozygous variant
      induced paclitaxel resistance due to altered HAT activity (p<0.001). This was
      reversed by the TSA combination. Restoration of wild BRCA2 from variant type
      improved paclitaxel sensitivity (p<0.001). Modulation of HAT activity by BRCA2
      N372H variation is a new mechanism of paclitaxel resistance in breast cancer.

PMID- 28431940
TI  - Immunoglobulin Infusion as Therapy Against Influenza?

PMID- 28431941
TI  - Bio-catalytic performance and dye-based industrial pollutants degradation
      potential of agarose-immobilized MnP using a Packed Bed Reactor System.
AB  - In this study, the matrix-entrapment technique was adopted to immobilize a novel
      manganese peroxidase (MnP). Agarose beads developed from 3.0% agarose
      concentration furnished the preeminent immobilization yield (92.76%). The
      immobilized MnP exhibited better resistance to changes in the pH and temperature
      as compared to the free counterpart, with optimal conditions being pH 6.0 and 45
      degrees C. Thermal and storage stability characteristics were significantly
      improved after immobilization, and the immobilized-MnP displayed higher tolerance
      against different temperatures than free MnP state. After 72h, the insolubilized
      MnP retained its activity up to 41.2+/-1.7% and 33.6+/-1.4% at 55 degrees C and
      60 degrees C, respectively, and 34.3+/-1.9% and 22.0+/-1.1% activities at 65
      degrees C and 70 degrees C, respectively, after 48h of the incubation period. A
      considerable reusability profile was recorded with ten consecutive cycles.
      Moreover, to explore the industrial applicability, the agarose-immobilized-MnP
      was tested for bioremediation of textile industry effluent purposes. After six
      consecutive cycles, the tested effluents were decolorized to different extents
      (with a maximum of 98.4% decolorization). In conclusion, the remarkable
      bioremediation potential along with catalytic, thermo-stability, reusability, as
      well as storage stability features of the agarose-immobilized-MnP reflect its
      prospects as a biocatalyst for bioremediation and other industrial applications.

PMID- 28431942
TI  - Chitosan-based nanocomplexes for simultaneous loading, burst reduction and
      controlled release of doxorubicin and 5-fluorouracil.
AB  - In this work, nanocomplexes based on chitosan grafted by carboxy-modified
      polylactic acid (SPLA) were prepared with the aim of loading simultaneously two
      anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their
      release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared
      by a polycondensation reaction, using pentetic acid as the core molecule, and
      linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded
      with both drugs were formulated by the polyelectrolyte complexation method. The
      structure of the SPLA was characterized by 1H NMR, while the product CS-SPLA was
      analyzed by FTIR-ATR to prove the occurrence of the reaction. Results showed that
      the diameters and zeta-potential of the nanocomplexes fall in the range 120-200nm
      and 20-37mV, respectively. SEM and TEM analysis confirmed the spherical shape and
      dimensions of the nanocomplexes. The presence of hydrophobic side chain SPLA did
      not influence the encapsulation efficiency of the drugs but strongly reduced the
      initial burst and prolonged release over time compared to unmodified chitosan. MS
      analysis showed that no degradation or interactions between the drugs and carrier
      were exhibited after loading or 24h of release had taken place, confirming the
      protective role of the nanocomplexes. In vitro tests demonstrated an increase in
      the cytotoxicity of the drugs when loaded in the prepared carriers.

PMID- 28431943
TI  - Expression and purification of p70DeltaCT104 S6 K, a 72kDa c-terminal truncated
      p70S6 kinase-GST fusion protein in bacterial expression system.
AB  - The p70DeltaCT104 S6K is a 421 amino acid residue long truncated form of p70S6
      kinase, with 104 amino acids residues cleaved from the carboxyl terminal end of
      the original protein. The p70DeltaCT104 S6K was cloned in E. coli DH5alpha and
      successfully expressed in E. coli BL21 (DE3) strain. Western blot with rabbit
      polyclonal anti-GST antibody was used to follow the protein during expression and
      purification. The protein purification was achieved by affinity chromatography
      using Glutathione resin-agarose beads, followed by chromatography on a spin
      concentration column. The purified protein was confirmed by rabbit polyclonal
      anti-p70S6 kinase antibody. MALDI/MS Peptide mass fingerprinting confirmed
      identity of the expressed product.

PMID- 28431944
TI  - Green seaweed Enteromorpha compressa (Chlorophyta, Ulvaceae) derived sulphated
      polysaccharides inhibit herpes simplex virus.
AB  - The herpes simplex virus (HSV) diseases represent a relevant medical and social
      problem due to their communicability and recurrence following latency. The green
      algae are rich source of polysaccharides referred to as ulvans, reported as being
      biologically and pharmacologically active. In this work, we analyzed the activity
      of seven chemically modified polysaccharides from Enteromorpha compressa
      (Chlorophyta, Ulvaceae), against HSV. Only the derivative named SU1F1 showed
      satisfactory viral inhibition activity, with a high selectivity index, and,
      therefore, it was submitted to analysis of the probable mechanism of action and
      structure. SU1F1 is a sulphated (22% w/w) heteroglycuronan with an apparent
      molecular mass of 34kDa. The antiviral activity was assayed by plaque reduction
      assay under the protocols of the time-of-addition (from 3h before infection to
      16h after infection), the inhibition of virus adsorption and penetration, and the
      virucidal effects. SU1F1 showed a high viral activity at the time 0h. We
      demonstrated that its inhibitory effect was maintained until 4h post-treatment
      with 100% of viral inhibition at 100MUg/ml. No effect was observed in additional
      protocols (the pre-treatment, the inhibition of adsorption and penetration and
      virucidal assays). Reverse Transcriptase associated PCR (RT-PCR) results were in
      accordance with plaque reduction assay and demonstrated the activity of SU1F1 at
      the initial stages of HSV replication.

PMID- 28431945
TI  - In vitro fermentation behaviors of fucosylated chondroitin sulfate from
      Pearsonothuria graeffei by human gut microflora.
AB  - A fucosylated chondroitin sulfate (FCS-pg) with highly repeated structure from
      Pearsonothuria graeffei was subjected to a in vitro fermentation model to
      investigate its fermentability and effects on human gut microflora. High
      performance liquid chromatography (HPLC) measurement found FCS-pg can be
      fermented to short chain fatty acids (SCFAs) by gut microflora from partial human
      fecal samples. 16S rRNA gene-based polymerase chain reaction-based denaturing
      gradient gel electrophoresis (PCR-DGGE) profiling and real-time quantitative PCR
      analysis showed that FCS-pg mainly increased the proportions of Clostridium
      cluster XI, Bacteriodes prevotella group, Bifidobacterium genus, Clostridium
      cluster I and Clostridium cluster XIVab, whereas the numbers of the
      Enterobacteriaceae and Lactobacillus decreased. These results indicated that FCS
      pg was mainly fermented by Bacteroides, Bifidobacterium and Clostridium. It
      increased the content of probiotics bacteria in achieving health-enhancing
      effect, was slightly different than most sulfated polysaccharides from marine
      animals. The current study provides useful new information on the mechanism of
      absorption and functional activity on FCS-pg within the gastrointestinal tract of
      the human body.

PMID- 28431946
TI  - Relationship between calorimetric profiles and differential melting curves for
      natural DNAs.
AB  - Many experiments demonstrate that regions with higher GC-content in natural DNAs
      unwind at higher temperatures adsorbing more heat than equivalently sized regions
      with lower GC-content. This simple observation implies that normalized
      calorimetric melting profiles (calorimetric cDMCs) will not be equivalent
      differential melting curves (DMCs). We propose simple expressions for long
      natural and random DNA sequences to reciprocally convert DMCs and corresponding
      calorimetric cDMCs. The expressions are confirmed by the Poland-Fixman-Freire
      method and an approach based upon mixtures of homopolymeric duplexes. Using these
      expressions and experimental calorimetric data, we demonstrate that the average
      relative deviation between DMC and cDMC is proportional to the temperature
      melting range of the helix-coil transition DeltaT. Corresponding difference
      between melting temperatures is proportional to DeltaT2. In general, sequence and
      ionic conditions influence the deviation through their effect on DeltaT. On the
      basis of the developed approach, we propose a method to determine the
      thermodynamic melting temperature (ratio of calorimetric enthalpy and entropy of
      the helix-coil transition) for natural DNAs from optical DMCs without
      calorimetric experiments.

PMID- 28431947
TI  - A bout analysis of operant response disruption.
AB  - Operant behavior appears to be organized in bouts of responses, whose parameters
      are differentially sensitive to various manipulations. This study investigated
      potential differential effects of three forms of operant response disruption
      extinction (EXT), non-contingent reinforcement (NCR), and prefeeding (PRE)-on
      response bouts. In Experiment 1, Wistar Kyoto rats (WKY) were trained on a tandem
      variable-time (VT) 120s fixed-ratio (FR) 5 schedule of reinforcement; after
      stability was established, their responding was disrupted for three sessions with
      one of the three disrupters (EXT, NCR, or PRE). In Experiment 2, Long Evans (LE)
      rats were trained on a tandem VT 240s FR 5 to stability, and their responding
      disrupted with EXT or NCR. In EXT and NCR, response rates declined significantly
      and progressively over the course of the session, primarily due to a declining
      bout-initiation rate in EXT, and to fewer responses per bout in NCR. In contrast,
      a session-wide drop in response rate was observed in PRE, primarily due to a
      reduction in bout-initiation rate at the start of the session. These findings
      suggest that each form of disruption differentially impacts dissociable aspects
      of behavior. Theories of behavioral persistence should account for these
      functional relations, which appear to be obscured in response rate measures.

PMID- 28431948
TI  - Serum peptides as putative modulators of inflammation in psoriasis.
AB  - BACKGROUND: Psoriasis is a refractory inflammatory disease, however, its
      pathophysiology is still not fully understood. OBJECTIVE: We tried to identify
      novel serum peptides associated with the pathophysiology of psoriasis. METHODS:
      Serum peptides from 24 patients with psoriasis vulgaris (PV), 10 patients with
      psoriatic arthritis (PsA), 14 patients with atopic dermatitis (AD), and 23
      healthy control (HC) subjects were analyzed by mass spectrometry. The effects of
      some peptides on the secretion of humoral factors from dermal cells were
      investigated by cytokine arrays and ELISAs. RESULTS: A total of 93 peptides were
      detected. 24, 20, 23, and 2 peptides showed at least 1.2-fold difference in ion
      intensity between the psoriasis (PV+PsA) and HC groups, between the PV+PsA and AD
      groups, between the PV and PsA groups, and between patients with severe-to
      moderate PV (n=6) and those with mild PV (n=18), respectively (p<0.05). 13 out of
      27 peptides that showed at least 1.5-fold ion intensity difference in the
      abovementioned 4 comparisons were identified. The parent proteins of the
      identified peptides included a coagulation factor, proteins involved in the
      maintenance of skin, and a protein relating to cytoskeleton. We focused on 2
      peptides that were increased in the PV+PsA group: a fibrinogen alpha chain
      derived peptide (1462m/z), the unmodified form of which was fibrinopeptide A-des
      alanine (FPAdA), and a filaggrin (FLG)-derived peptide (1977m/z), a modified form
      of FLG2099-2118 (Q2099pE, Q2115E; FLG-pEE). FPAdA stimulation increased the
      secretion of GROalpha from dermal microvascular endothelial cells (dMVECs) and
      decreased the secretion of lipocalin-2 from keratinocytes in comparison to FPAdA
      resequenced peptide stimulation (GROalpha, 280.9+/-7.3pg/mL vs. 229.6+/-5.0pg/mL,
      p<0.001; lipocalin-2, 273+/-13pg/mL vs. 350+/-10pg/mL, p<0.01). Interestingly,
      FLG-pEE stimulation decreased the secretion of GROalpha, IL-8, and MCP-1 from
      dMVECs in comparison to FLG-derived control peptide stimulation (GROalpha,
      844.3+/-47.5pg/mL vs. 1038.5+/-96.9pg/mL, p<0.05; IL-8, 2240.1+/-172.6pg/mL vs.
      3221.8+/-523.7pg/mL, p<0.05; MCP-1, 4057.8+/-157.2pg/mL vs. 4619.1+/-213.4pg/mL,
      p<0.05). CONCLUSIONS: The results suggested that some serum peptides are involved
      in the pathophysiology of psoriasis, regulating the secretion of inflammatory
      chemokines and an antimicrobial protein. The modulation of serum peptides may be
      a potential therapeutic strategy for psoriasis.

PMID- 28431949
TI  - Classification of EEG signals to identify variations in attention during motor
      task execution.
AB  - BACKGROUND: Brain-computer interface (BCI) systems in neuro-rehabilitation use
      brain signals to control external devices. User status such as attention affects
      BCI performance; thus detecting the user's attention drift due to internal or
      external factors is essential for high detection accuracy. NEW METHOD: An
      auditory oddball task was applied to divert the users' attention during a simple
      ankle dorsiflexion movement. Electroencephalogram signals were recorded from
      eighteen channels. Temporal and time-frequency features were projected to a lower
      dimension space and used to analyze the effect of two attention levels on motor
      tasks in each participant. Then, a global feature distribution was constructed
      with the projected time-frequency features of all participants from all channels
      and applied for attention classification during motor movement execution.
      RESULTS: Time-frequency features led to significantly better classification
      results with respect to the temporal features, particularly for electrodes
      located over the motor cortex. Motor cortex channels had a higher accuracy in
      comparison to other channels in the global discrimination of attention level.
      COMPARING WITH EXISTING METHODS: Previous methods have used the attention to a
      task to drive external devices, such as the P300 speller. However, here we focus
      for the first time on the effect of attention drift while performing a motor
      task. CONCLUSIONS: It is possible to explore user's attention variation when
      performing motor tasks in synchronous BCI systems with time-frequency features.
      This is the first step towards an adaptive real-time BCI with an integrated
      function to reveal attention shifts from the motor task.

PMID- 28431950
TI  - Postoperative adjuvant chemotherapy is associated with a lower incidence of
      colorectal adenomas in patients with previous colorectal cancer.
AB  - BACKGROUND AND AIMS: The effects of chemotherapeutic agents on the development of
      colorectal adenomas in patients with previous colorectal cancer (CRC) are not
      defined. Therefore, we evaluated the potential effect of adjuvant chemotherapy on
      the incidence of colorectal adenomas in patients with previous CRC. METHODS: We
      selected patients with low-risk stage II CRC with or without postoperative 5
      fluorouracil-based adjuvant chemotherapy to reduce selection bias. Among 1808
      patients with stage II CRC who underwent colonoscopic surveillance after curative
      resection of CRC between 2006 and 2013, 192 patients were retrospectively
      enrolled in this study after matching for age and sex. The patients were divided
      into 96 patients receiving and 96 patients not receiving 5-fluorouracil-based
      chemotherapy. RESULTS: Forty patients (41.7%) exhibited colorectal adenomas among
      96 patients who received adjuvant chemotherapy, compared with 50 patients (52.1%)
      with colorectal adenomas among 96 patients who received surgery only. The
      incidence rate of advanced adenoma was significantly lower in the chemotherapy
      group than in the nonchemotherapy group (3.1% vs 10.4%, P = .044). After
      adjustment for clinically relevant factors such as body mass index, aspirin use,
      metformin use, number of follow-up colonoscopies, and operation type, adjuvant
      chemotherapy was found to be associated with a decreased incidence of advanced
      adenoma (odds ratio, .151; 95% confidence interval, .035-.653; P = .011) in
      patients with stage II CRC. CONCLUSIONS: The results showed that chemotherapy in
      patients with CRC may be associated with a lower risk of colorectal advanced
      adenoma development.

PMID- 28431951
TI  - Public health impact of colonoscopy use on colorectal cancer mortality in Germany
      and the United States.
AB  - BACKGROUND AND AIMS: Colonoscopy has been demonstrated to be effective in
      reducing colorectal cancer (CRC) incidence and mortality and has been widely used
      for primary CRC screening in Germany and the United States. We performed a
      population-based analysis to evaluate and compare the public health impact of
      recent colonoscopy use on CRC deaths among adults aged 55 to 79 years in Germany
      and the United States from 2008 to 2011. METHODS: The epidemiologic metrics of
      attributable fraction and prevented fraction as well as the impact numbers were
      calculated using colonoscopy utilization data from nationally representative
      health surveys, relative risk estimates from medical literature, and CRC death
      registry data. RESULTS: Overall, 36.6% (95% credible interval [CrI], 27.3%-45.5%)
      of CRC deaths in Germany were estimated to be attributable to nonuse of
      colonoscopy, compared with the U.S. estimates of 38.2% (95% CrI, 28.6%-47.1%) and
      33.6% (95% CrI, 24.8%-42.2%) for years 2008 to 2009 and 2010 to 2011,
      respectively. The proportion of CRC deaths theoretically prevented by colonoscopy
      use within 10 years was 30.7% (95% CrI, 24.8%-35.7%) in Germany, whereas in the
      United States this proportion ranged from 29.0% (95% CrI, 23.4%-33.6%) for 2008
      to 2009 to 33.9% (95% CrI, 27.4%-39.2%) for 2010 to 2011. CONCLUSIONS: Recent
      colonoscopy use is likely to have prevented a considerable fraction of CRC
      mortality in both countries, and more deaths could be avoided by increasing
      colonoscopy use in the target population. Attributable and prevented fraction can
      provide valuable information on the public health impact of colonoscopy use and
      guide policymaking.

PMID- 28431952
TI  - Evaluation of patient preparedness for surgery: a randomized controlled trial.
AB  - BACKGROUND: Patient preparedness for pelvic reconstructive surgery has important
      implications for patient satisfaction and the perception of improvement after
      surgery. The ideal method in which to optimally prepare patients for surgery has
      not been determined. OBJECTIVE: The objective of the study was to evaluate the
      impact of a preoperative patient education video on patient preparedness prior to
      sacrocolpopexy as measured by a preoperative preparedness questionnaire. STUDY
      DESIGN: We performed a single-blind, randomized, stratified clinical trial at a
      single academic center evaluating the use of a preoperative patient education
      video as an adjunct to preoperative counseling on patient preparedness. Eligible
      patients presenting for their preoperative appointment prior to undergoing pelvic
      reconstructive surgery were randomized to watch a preoperative video vs usual
      care. Preoperative questionnaires assessing patient preparedness, understanding,
      perception of time, and actual time spent with a health care team were
      administered at the end of this visit. The primary outcome was patient
      preparedness for pelvic reconstructive surgery as measured by a preoperative
      preparedness questionnaire. Secondary outcomes included actual time spent during
      the physician-patient encounter, perception of time spent with the health care
      team, and identification of patient factors associated with patient preparedness.
      RESULTS: Of the total 100 recruited patients, 52 were randomized to the video
      group and 48 to the usual-care group. The use of the video did not increase
      overall patient preparedness (71.1% with video vs 68.8% usual care, P = .79)
      prior to surgery. The use of the video did not decrease the amount of time spent
      during the physician-patient encounter (16.9 +/- 5.6 min vs 17.1 +/- 5.4 min, P =
      .87). There was a significant association between patient preparedness and
      perception that the health care team spent sufficient time with the patient
      (89.5% vs 10.5%; P < .001), but no association was observed between preparedness
      and actual time spent (17.4 +/- 5.4 min vs16.5 +/- 5.5 min, P = .47). Those with
      a history of a previous surgery (82.1% vs 33.3%, P = .002) and those with more
      significant apical prolapse (0.6 +/- 4.6 vs -1.6 +/- 3.9, P = .05) were more
      likely to report feeling prepared for surgery. CONCLUSION: The majority of
      patients undergoing pelvic surgery at our institution felt prepared prior to
      undergoing surgery. The use of preoperative education video did not increase
      overall patient preparedness for surgery. Greater preparedness was associated
      with patient perception of how much time the health care team spent with the
      patient but not actual time spent.

PMID- 28431953
TI  - Cryostored autologous skull bone for cranioplasty? A study on cranial bone flaps'
      viability and microbial contamination after deep-frozen storage at -80 degrees C.
AB  - Craniectomy is a life-saving procedure. Subsequent cranioplasty with autologous
      skull bone has a bone resorption rate from 4% to 22.8% and an infection rate from
      3.3% to 26%. There are concerns with their viability and the potential microbial
      contamination as they were explanted for a long period of time. Eighteen cranial
      bone flaps stored at Prince of Wales Hospital Skull Bone Bank during the period
      from June 2011 to March 2016 were identified. Ethics approval was obtained. Bone
      chips and deep bone swabs were collected for osteoblast culture and microbial
      culture. Skull Bone Bank was kept at -80 degrees C under strict aseptic technique
      during the study period. The storage period ranged from 4months to 55months. For
      the osteoblast culture, all eighteen bone flaps had no viable osteoblast growth.
      For the bacterial culture, five had positive bacteria growth (27.8%). Three were
      Pasteurella multocida and two were Methicillin-resistant Staphylococcus aureus.
      The mean duration of storage of the infected bone flap was 32.9months (+/
      15.1months) versus 19.9months (+/-17.9months) of those bone flaps with no
      bacterial growth (p=0.1716). The mean size of the infected versus non-infected
      bone flaps was 117.7cm2 (+/-44.96cm2) versus 76.8cm2 (+/-50.24cm2) respectively
      (p=0.1318). Although in this study statistical significance was not reached, it
      was postulated that infected bone flaps tended to be larger in size and had a
      longer duration of storage. In conclusion, cryostored skull bone flaps beyond
      four months showed no viable osteoblasts. Bacterial contamination rate of bone
      flaps was 27.8% in this study.

PMID- 28431954
TI  - Isolated intracranial fibromuscular dysplasia of the posterior cerebral artery.
AB  - Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory arterial
      disease that most commonly affects the renal and internal carotid arteries, but
      intracranial FMD is very rare. We report a patient with FMD involving the
      posterior cerebral arteries (PCAs). A 24year old female was presented with a 4day
      history of right homonymous hemianopsia with throbbing headache in the left
      temporo-occipital area. The brain magnetic resonance imaging (MRI) revealed an
      acute ischemic stroke in the left PCA territory, while the Time of Flight (TOF)
      magnetic resonance angiogram (MRA) showed segmental luminal irregularities in the
      left proximal PCA. The conventional angiogram revealed the "string of beads"
      appearance, a characteristic that is pathognomonic for FMD. The patient's
      inhospital clinical course was stable, while there was no recurrence of stroke.
      This is the second report of FMD of the PCA. Notwithstanding incredibly rare
      incidences of isolated intracranial FMD and nonspecific findings of MRA, such a
      pathophysiology should be considered as the cause for a stroke in young patients,
      especially those with no cardiovascular risk factor.

PMID- 28431955
TI  - The course of Modic vertebral body changes after posterolateral lumbar fusion on
      fused and adjacent levels: A systematic review of the literature.
AB  - According to the original description by Modic et al., the natural course of bone
      marrow signal abnormalities is an inexorable, progressive one, however recent
      evidence has demonstrated in healthy individuals and those suffering from lumbar
      disc herniation that the course of endplate degenerative changes is rather
      dynamic and sometimes regressive. The evolution of such changes in lumbar fused
      segments and adjacent levels is largely unknown. The literature relevant to the
      course of Modic changes on fused and adjacent levels, as well as its clinical
      correspondence in patients undergoing posterolateral lumbar fusion was collected.
      Two studies met the criteria. Of 38 patients with Modic type I signals
      preoperatively, 6 regressed to type 0, 22 progressed to type 2, and 10 remained
      the same postoperatively. Of 12 patients with Modic type 2 signals
      preoperatively, 2 regressed to type 0 and 10 remained the same postoperatively.
      None of the articles described the Modic changes in adjacent levels. Clinical and
      functional outcomes were significantly improved at follow-up regardless of the
      endplate signal changes. The best available evidence points out to a reduction in
      Modic type I frequency on fused segments, either regressive or progressive. There
      was a predominance of new type II changes in postoperative images, which might
      represent improvement of instability. This study calls into attention the
      controversial role of Modic changes as an indicator of clinical significance,
      since clinical and functional outcomes significantly improved regardless of the
      endplate signal changes.

PMID- 28431956
TI  - Bilateral cerebral embolism as a characteristic feature of patients with
      Trousseau syndrome.
AB  - Trousseau syndrome is defined as a variant of intravascular thromboembolism that
      is induced by cancer. It may manifest itself as cerebral embolisms in some cases;
      however, when the cancer is not diagnosed, this identification may be difficult.
      Therefore, cerebral embolisms are often treated without identifying the cancer,
      which can worsen a patient's condition. The purpose of this study was to
      determine the differences in clinical features between cerebral embolisms induced
      by cancer (Trousseau syndrome) and those that are due to other causes, such as
      cardiogenic embolisms and artery-to-artery stroke. A total of 83 patients,
      admitted to our hospital between April 2005 and March 2013 with cerebral
      embolisms, were included in this study. Of these, 9 (10.8%) were diagnosed with
      Trousseau syndrome, 63 (75.9%) had cardiogenic embolisms and 11 (13.2%) had
      artery-to-artery embolisms. Patients with embolic stroke of undetermined source
      (ESUS) were excluded from the study. We retrospectively investigated the
      localization of the infarctions, cancer type, and pathology, and the levels of
      primary fibrin/fibrinogen degradation products (FDP). From the nine patients with
      Trousseau syndrome, eight had adenocarcinomas and all had elevated initial FDP.
      Bilateral cerebral embolisms were significantly more common in Trousseau syndrome
      patients than cardiogenic embolisms (P=0.00026) and artery-to-artery embolisms
      (P=0.0016). All of them contained microembolisms as observed by magnetic
      resonance imaging (MRI). This study suggests that bilateral infarctions
      presenting microembolisms are important features of cerebral embolism attributed
      to Trousseau syndrome.

PMID- 28431957
TI  - Genetic study of KIR and HLA ligands in 235 individuals from Northeastern
      Thailand.
AB  - The diversity of 17 KIR and HLA ligands (HLA-C1, C2, Bw4, A11) were investigated
      in two hundred and thirty-five unrelated healthy donors in Northeastern Thais
      (NETs) by the polymerase chain reaction with sequence-specific primer (PCR-SSP)
      method. The Hardy-Weinberg Equilibrium (HWE) was used to verify genotyping method
      for dimorphic KIR and HLA. They were in HWE (p>0.05). KIR and HLA ligands
      frequencies, genotypes, haplotypes and linkage disequilibrium (LD) were
      presented. The genetic data are available in allele Frequencies Net Database.

PMID- 28431958
TI  - Nomenclature for factors of the HLA system, update January 2017.

PMID- 28431959
TI  - Nomenclature for factors of the HLA system, update February 2017.

PMID- 28431960
TI  - Nomenclature for factors of the HLA system, update March 2017.

PMID- 28431961
TI  - Ionizing radiation induces long-term senescence in endothelial cells through
      mitochondrial respiratory complex II dysfunction and superoxide generation.
AB  - Ionizing radiation causes oxidative stress, leading to acute and late cellular
      responses. We previously demonstrated that irradiation of non-proliferating
      endothelial cells, as observed in normal tissues, induces early apoptosis, which
      can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to
      better characterize the long-term radiation response of endothelial cells by
      studying the molecular pathways associated with senescence and its link with
      acute apoptosis. First, senescence was validated in irradiated quiescent
      microvascular HMVEC-L in a dose- and time-dependent manner by SA beta
      galactosidase staining, p16Ink4a and p21Waf1 expression, pro-inflammatory IL-8
      secretion and DNA damage response activation. This premature aging was induced
      independently of Sphingosine 1-Phosphate treatment, supporting its non-connection
      with acute IR-induced apoptosis. Then, senescence under these conditions showed
      persistent activation of p53 pathway and mitochondrial dysfunctions,
      characterized by O2.- generation, inhibition of respiratory complex II activity
      and over-expression of SOD2 and GPX1 detoxification enzymes. Senescence was
      significantly inhibited by treatment with pifithrin-alpha, a p53 inhibitor, or by
      MnTBAP, a superoxide dismutase mimetic, validating those molecular actors in IR
      induced endothelial cell aging. However, MnTBAP, but not pifithrin-alpha, was
      able to limit superoxide generation and to rescue the respiratory complex II
      activity. Furthermore, MnTBAP was not modulating p53 up-regulation, suggesting
      that IR-induced senescence in quiescent endothelial cells is provided by at least
      2 different pathways dependent of the mitochondrial oxidative stress response and
      the p53 activation. Further characterization of the actors involved in the
      respiratory complex II dysfunction will open new pharmacological strategies to
      modulate late radiation toxicity.

PMID- 28431962
TI  - Structural basis, chemical driving forces and biological implications of flavones
      as Cu(II) ionophores.
AB  - A main biochemical property of cancer cells, compared with normal cells, is
      altered redox status including increased levels of copper to maintain their
      malignant phenotypes. Thus, increasing copper accumulation, by using ionophores,
      to disrupt abnormal redox homeostasis of cancer cells may be an important
      anticancer strategy. Naturally occurring molecules with extraordinarily diverse
      chemical scaffolds are an important source of inspiration for developing copper
      ionophores. Dietary flavonoids are well-characterized copper chelators and show
      cancer chemopreventive potential, but their ionophoric role for redox-active
      copper and the related biological implications have remained unknown. This study
      reports, for the first time, the structural basis, chemical driving forces and
      biological implications of flavones (a widely distributed subgroup of flavonoids)
      as Cu(II) ionophores, and also provides new insights into cancer chemopreventive
      mechanism of flavones bearing 3(or 5)-hydroxy-4-keto group. 3-Hydroxyflavone
      surfaced as a potent Cu(II) ionophore to induce the mitochondria-dependent
      apoptosis of cancer cells in a redox intervention fashion via sequential proton
      loss Cu(II) chelation, GSH-driving releasing of copper and protonation-dependent
      efflux of the neutral ligand.

PMID- 28431963
TI  - Expansion of circulating follicular T helper cells associates with disease
      severity in childhood atopic dermatitis.
AB  - Follicular helper T (TFH) cells play crucial role in B-cell differentiation and
      antibody production. Although, atopic dermatitis (AD) is often associated with
      increased serum IgE levels, B-cell mediated responses have not been studied
      thoroughly. The aim of our study was to investigate the proportion of TFH-like
      cells in the disease. Twelve children and 17 adults with AD as well as 14 healthy
      controls were enrolled in the study. The frequency of CD4+CXCR5+ICOS+PD-1+ TFH
      like cells and their IL-21 cytokine production were determined by flow cytometry.
      Immunohistochemical analysis was performed on skin biopsy specimens from AD
      patients for the detection of TFH markers. The percentages and absolute numbers
      of circulating TFH-like cells were significantly increased in children with AD
      compared to adult patients and healthy controls. IL-21 cytokine production of TFH
      like cells was also elevated and showed a strong positive correlation with
      paediatric patients' SCORAD index. The expression of TFH-specific markers showed
      only a non-specific scattered pattern in skin biopsy specimens. This is the first
      study to demonstrate that TFH-like cells expanded in the peripheral blood of
      children with AD compared to adults. These results reinforce the importance of
      further investigations on TFH-like cells in different phenotypes and endotypes of
      AD.

PMID- 28431964
TI  - Microvillus-Specific Protein Tyrosine Phosphatase SAP-1 Plays a Role in
      Regulating the Intestinal Paracellular Transport of Macromolecules.
AB  - The stomach cancer-associated protein tyrosine phosphatase 1 (SAP-1) is a
      receptor-type protein tyrosine phosphatase that is specifically expressed on the
      apical membrane of the intestinal epithelium. SAP-1 is known to maintain the
      balance of phosphorylation of proteins together with protein kinases; however,
      its biological function and impact on pharmacokinetics in the intestine remain
      unclear. The present study, therefore, aimed at clarifying the relationship
      between SAP-1 and the intestinal absorption behaviors of typical transporter
      substrates and macromolecules. The endogenous levels of glucose and total
      cholesterol in the blood were similar between wild-type and SAP-1-deficient mice
      (Sap1-/-), suggesting no contribution of SAP-1 to biogenic influx. Moreover, in
      vitro transport study with everted ileal sacs demonstrated that there was no
      difference in the absorption of breast cancer resistance protein, P-glycoprotein,
      and peptide transporter substrates between both mice. However, absorptive
      clearance of macromolecular model dextrans (FD-4 and FD-10) in Sap1-/- mice was
      significantly higher than that in wild-type mice, and this was confirmed by the
      trend of increased FD-4 absorption from colonic loops of Sap1-/- mice. Therefore,
      the results of this study suggest the partial contribution of SAP-1 to the
      regulated transport of hydrophilic macromolecules through paracellular tight
      junctions.

PMID- 28431965
TI  - Origin of Nanodroplet Formation Upon Dissolution of an Amorphous Solid
      Dispersion: A Mechanistic Isotope Scrambling Study.
AB  - It has been observed that certain amorphous solid dispersions (ASDs), upon
      dissolution, generate drug-rich amorphous nanodroplets. These nanodroplets,
      present as a dispersed phase, can potentially enhance oral bioavailability of
      poorly soluble drugs by serving as a drug reservoir that efficiently feeds the
      continuous aqueous solution phase following absorption of drug. The purpose of
      this study is to probe the formation mechanism of the nanodroplets. The model
      system studied was nifedipine (NFD) formulated as an ASD with hydroxypropyl
      methylcellulose E5 Premium LV or polyvinylpyrrolidone/vinyl acetate. Dissolution
      of ASDs prepared with proteated nifedipine (H-NFD) was carried out in a medium
      saturated with deuterated nifedipine (D-NFD) at the amorphous solubility. Upon
      dissolution, the H/D composition of NFD aqueous solution was determined using
      nuclear magnetic resonance spectroscopy. The results suggested that isotopic
      scrambling (equilibrium in the distribution of deuterated and proteated form of
      the drug) had occurred. Thus, as the H-NFD was brought into the aqueous solution
      via ASD dissolution, the drug concentration in solution exceeded the amorphous
      solubility. Subsequent precipitation of the drug, a process which does not
      differentiate H-NFD from D-NFD, generated NFD nanodroplets and resulted in
      redistribution of the isotopes. Thus, nanodroplets of NFD are formed due to
      dissolution of these homogenous ASDs followed by precipitation of the drug from
      aqueous solutions.

PMID- 28431966
TI  - Spray Drying as a Reliable Route to Produce Metastable Carbamazepine Form IV.
AB  - Carbamazepine (CBZ) is an active pharmaceutical ingredient used in the treatment
      of epilepsy that can form at least 5 polymorphic forms. Metastable form IV was
      originally discovered from crystallization with polymer additives; however, it
      has not been observed from subsequent solvent-only crystallization efforts. This
      work reports the reproducible formation of phase pure crystalline form IV by
      spray drying of methanolic CBZ solution. Characterization of the material was
      carried out using diffraction, scanning electron microscopy, and differential
      scanning calorimetry. In situ Raman spectroscopy was used to monitor the spray
      dried product during the spray drying process. This work demonstrates that spray
      drying provides a robust method for the production of form IV CBZ, and the
      combination of high supersaturation and rapid solid isolation from solution
      overcomes the apparent limitation of more traditional solution crystallization
      approaches to produce metastable crystalline forms.

PMID- 28431967
TI  - Family-centered prevention ameliorates the association between adverse childhood
      experiences and prediabetes status in young black adults.
AB  - Individuals exposed to adverse childhood experiences (ACEs) are vulnerable to
      various health problems later in life. This study was designed to determine
      whether participation in an efficacious program to enhance supportive parenting
      would ameliorate the association between ACEs and prediabetes status at age 25.
      Rural African American parents and their 11-year-old children (N=390)
      participated in the Strong African American Families (SAAF) program or a control
      condition. Each youth at age 25 provided a total ACEs score and a blood sample
      from which overnight fasting glucose was assayed. Logistic regression equations
      were used to test the hypotheses. The logistic regression analyses revealed a
      significant interaction between total ACEs and random assignment to SAAF or
      control, OR=0.56, 95% CI [0.36, 0.88]. Follow-up analyses indicated that, for
      participants in the control condition, a 1-point increase in ACEs was associated
      with a 37.3% increase in risk of having prediabetes. ACEs were not associated
      with the likelihood of having prediabetes among participants in the SAAF
      condition. Control participants with high total ACEs scores were 3.54 times more
      likely to have prediabetes than were SAAF participants with similar scores. This
      study indicated that participation at age 11 in a randomized controlled trial
      designed to enhance supportive parenting ameliorated the association of ACEs with
      prediabetes at age 25. If substantiated, these findings may provide a strategy
      for preventing negative health consequences of ACEs.

PMID- 28431968
TI  - Cannabinoid CB1 and CB2 receptors differentially modulate L- and T-type Ca2+
      channels in rat retinal ganglion cells.
AB  - Endocannabinoid signaling system is involved in regulating multiple neuronal
      functions in the central nervous system by activating G-protein coupled
      cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown
      that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs).
      Here, modulation of L- and T-types Ca2+ channels by activating CB1Rs and CB2Rs in
      RGCs was investigated. Triple immunofluorescent staining showed that L-type
      subunit CaV1.2 was co-localized with T-type subunits (CaV3.1, CaV3.2 and CaV3.3)
      in rat RGCs. In acutely isolated rat RGCs, the CB1R agonist WIN55212-2 suppressed
      both peak and steady-state Ca2+ currents in a dose-dependent manner, with IC50
      being 9.6 MUM and 8.4 MUM, respectively. It was further shown that activation of
      CB1Rs by WIN55212-2 or ACEA, another CB1R agonist, significantly suppressed both
      L- and T-type Ca2+ currents, and shifted inactivation curve of T-type one toward
      hyperpolarization direction. While the effect on L-type Ca2+ channels was
      mediated by intracellular cAMP/protein kinase A (PKA), mitogen-activated protein
      kinase (MAPK)/extracellular signal-regulated kinase (ERK) and calcium/calmodulin
      dependent protein kinase II (CaMKII) signaling pathways, only CaMKII signaling
      pathway was involved in the effect on T-type Ca2+ channels. Furthermore, CB65 and
      HU308, two specific CB2R agonists, significantly suppressed T-type Ca2+ channels,
      which was mediated by intracellular cAMP/PKA and CaMKII signaling pathways, but
      had no effect on L-type channels. These results imply that endogenous
      cannabinoids may modulate the excitability and the output of RGCs by
      differentially suppressing the activity of L- and T-type Ca2+ channels through
      activation of CB1Rs and CB2Rs. This article is part of the Special Issue entitled
      "A New Dawn in Cannabinoid Neurobiology".

PMID- 28431969
TI  - CRFR1 in the ventromedial caudate putamen modulates acute stress-enhanced
      expression of cocaine locomotor sensitization.
AB  - Repeated exposure to psychostimulants induces a long-lasting enhancement of
      locomotor activity called behavioral sensitization, which is often reinforced by
      stress after drug withdrawal. The mechanisms underlying these phenomena remain
      elusive. Here we explored the effects of acute stress 3 or 14 days after the
      cessation of chronic cocaine treatment on the expression of locomotor
      sensitization induced by a cocaine challenge in rats and the key brain region and
      molecular mechanism underlying the phenomenon. A single session of forced
      swimming, as an acute stress (administered 2 days after the cessation of
      cocaine), significantly enhanced the expression of cocaine locomotor
      sensitization 14 days after the final cocaine injection (challenge at 12 days
      after acute stress) but not 3 days after the cessation of cocaine (challenge at 1
      day after acute stress). The result indicated that acute stress enhanced the
      expression of cocaine locomotor sensitization after incubation for 12 days rather
      than 1 day after the last cocaine injection. Moreover, the enhancement in
      locomotor sensitization was paralleled by a selective increase in the number of
      the c-Fos+ cells, the level of CRFR1 mRNA in the ventromedial caudate putamen
      (vmCPu). Furthermore, the enhancement was significantly attenuated by CRFR1
      antagonist NBI-27914 into the vmCPu, implying that the up-regulation of CRFR1 in
      the vmCPu seems to be critical in the acute stress-enhanced expression of cocaine
      locomotor sensitization. The findings demonstrate that the long-term effect of
      acute stress on the expression of cocaine locomotor sensitization is partially
      mediated by CRFR1 in the vmCPu.

PMID- 28431970
TI  - Effects of natural and synthetic isothiocyanate-based H2S-releasers against
      chemotherapy-induced neuropathic pain: Role of Kv7 potassium channels.
AB  - Hydrogen sulfide (H2S) is a crucial signaling molecule involved in several
      physiological and pathological processes. Nonetheless, the role of this
      gasotransmitter in the pathogenesis and treatment of neuropathic pain is
      controversial. The aim of the present study was to investigate the pain relieving
      profile of a series of slow releasing H2S donors (the natural allyl
      isothiocyanate and the synthetics phenyl- and carboxyphenyl-isothiocyanate) in
      animal models of neuropathic pain induced by paclitaxel or oxaliplatin,
      anticancer drugs characterized by a dose-limiting neurotoxicity. The potential
      contribution of Kv7 potassium channels modulation was also studied. Mice were
      treated with paclitaxel (2.0 mg kg-1) i.p. on days 1, 3, 5 and 7; oxaliplatin
      (2.4 mg kg-1) was administered i.p. on days 1-2, 5-9, 12-14. Behavioral tests
      were performed on day 15. In both models, single subcutaneous administrations of
      H2S donors (1.33, 4.43, 13.31 MUmol kg-1) reduced the hypersensitivity to cold
      non-noxious stimuli (allodynia-related measurement). The prototypical H2S donor
      NaHS was also effective. Activity was maintained after i.c.v. administrations. On
      the contrary, the S-lacking molecule allyl-isocyanate did not increase pain
      threshold; the H2S-binding molecule hemoglobin abolished the pain-relieving
      effects of isothiocyanates and NaHS. The anti-neuropathic properties of H2S
      donors were reverted by the Kv7 potassium channel blocker XE991. Currents carried
      by Kv7.2 homomers and Kv7.2/Kv7.3 heteromers expressed in CHO cells were
      potentiated by H2S donors. Sistemically- or centrally-administered
      isothiocyanates reduced chemotherapy-induced neuropathic pain by releasing H2S.
      Activation of Kv7 channels largely mediate the anti-neuropathic effect.

PMID- 28431972
TI  - Mitochondrial energy metabolism of rat hippocampus after treatment with the
      antidepressants desipramine and fluoxetine.
AB  - Alterations in mitochondrial functions have been hypothesized to participate in
      the pathogenesis of depression, because brain bioenergetic abnormalities have
      been detected in depressed patients by neuroimaging in vivo studies. However,
      this hypothesis is not clearly demonstrated in experimental studies: some suggest
      that antidepressants are inhibitors of mitochondrial metabolism, while others
      observe the opposite. In this study, the effects of 21-day treatment with
      desipramine (15 mg/kg) and fluoxetine (10 mg/kg) were examined on the energy
      metabolism of rat hippocampus, evaluating the catalytic activity of regulatory
      enzymes of mitochondrial energy-yielding metabolic pathways. Because of the micro
      heterogeneity of brain mitochondria, we have distinguished between (a) non
      synaptic mitochondria (FM) of neuronal perikaryon (post-synaptic compartment) and
      (b) intra-synaptic light (LM) and heavy (HM) mitochondria (pre-synaptic
      compartment). Desipramine and fluoxetine changed the catalytic activity of
      specific enzymes in the different types of mitochondria: (a) in FM, both drugs
      enhanced cytochrome oxidase and glutamate dehydrogenase, (b) in LM, the overall
      bioenergetics was unaffected and (c) in HM only desipramine increased malate
      dehydrogenase and decreased the activities of Electron Transport Chain Complexes.
      These results integrate the pharmacodynamic features of desipramine and
      fluoxetine at subcellular level, overcoming the previous conflicting data about
      the effects of antidepressants on brain energy metabolism, mainly referred to
      whole brain homogenates or to bulk of cerebral mitochondria. With the
      differentiation in non-synaptic and intra-synaptic mitochondria, this study
      demonstrates that desipramine and fluoxetine lead to adjustments in the
      mitochondrial bioenergetics respect to the energy requirements of pre- and post
      synaptic compartments.

PMID- 28431973
TI  - Understanding the Relationship of Cigarette Smoking Trajectories Through
      Adolescence and Weight Status in Young Adulthood in the United States.
AB  - PURPOSE: Adolescent cigarette smoking has steadily declined since 1999, whereas
      adolescent obesity rates have quadrupled since the 1980s. Few studies address the
      longitudinal relationship of smoking and weight in youth and young adulthood.
      This study examines the relationship of smoking trajectories beginning in
      adolescence on weight status in young adulthood in a nationally representative
      longitudinal sample. METHODS: The study sample was drawn from the National
      Longitudinal Study of Adolescent to Adult Health Waves I-IV (N = 13,361). Four
      trajectories were generated through repeated-measures latent class analyses using
      current cigarette smoking status in Waves I-IV and age of initiation: nonsmokers
      (44%), early establishers (23%), late establishers (21%), and former smokers
      (12%). Wave IV weight status included self-reported body mass index (BMI) and
      measured waist circumference. Bivariate analyses addressed associations between
      smoking trajectory and BMI at each wave. Multivariate linear regression models
      tested the relationship of smoking trajectory and weight status at Wave IV.
      RESULTS: In bivariate analyses, early and late establishers had a significantly
      lower BMI at Wave III and all smoking trajectories had a significantly lower BMI
      at Wave IV versus nonsmokers. All smoking trajectories had a significantly lower
      BMI than nonsmokers (early establishers: beta = -1.27, confidence interval [CI]: 
      1.56 to -.98]; late establishers: beta = -.84, CI: -1.16 to -.52; and former
      smokers: beta = -.63, CI: -.93 to -.34; p < .05) in an adjusted multivariable
      regression model. CONCLUSIONS: This study reveals that weight status increased
      over time for all trajectories; thus smoking does not mitigate obesity risk.
      These results have implications for both research and interventions to help youth
      and young adults avoid both smoking and obesity.

PMID- 28431974
TI  - Unique mitochondrial localization of arginase 1 and 2 in hepatocytes of air
      breathing walking catfish, Clarias batrachus and their differential expression
      patterns under hyper-ammonia stress.
AB  - Arginase (ARG) catalyzes the final step of ornithine-urea cycle (OUC) leading to
      a conversion of L-arginine to L-ornithine and urea. Several isoforms of ARG have
      been reported in vertebrates, out of which the two predominant isoforms are the
      cytosolic ARG1 and the mitochondrial ARG2. The air-breathing walking catfish
      (Clarias batrachus) is frequently being challenged by different environmental
      insults such as hyper-ammonia, dehydration and osmotic stresses in their natural
      habitats throughout the year. The present study investigated the active presence
      of ARG1 and ARG2 isoforms in hepatocytes along with unique localization of both
      the isoforms inside the mitochondria, and also their specific expression patterns
      under hyper-ammonia stress (5mM NH4Cl) in isolated hepatocytes of walking
      catfish. Initially, full length sequences of both arg1 and arg2 genes were
      obtained by RACE-PCR. Studies on molecular characterization demonstrated the
      presence of all the conserved amino acids required for stability and activity of
      binuclear metal center in both the isoforms. Phylogenetic analysis of the amino
      acid sequences of ARG isoforms showed a differentiation of the ARG1 and ARG2 into
      two distinct clusters with their respective isoforms from other species. Most
      interestingly, both the isoforms of ARG in hepatocytes were found to be localized
      inside the mitochondria as evidenced by the presence of mitochondrial target
      peptide (mTP) in N-terminal of the derived amino acid sequences, and exclusive
      localization of ARG activity in the mitochondrial fraction. This was additionally
      confirmed by Western blot analysis of ARGs in mitochondrial and cytosolic
      fractions, and by immunocytochemical analysis in isolated hepatocytes. Although
      the possible reasons associated with the presence of both the isoforms of ARGs
      inside the mitochondria is not clearly understood, perhaps this mitochondrial
      localization of ARG is functionally advantageous in this catfish for the
      synthesis of N-acetyl-l-glutamate, the allosteric regulator for the first OUC
      enzyme, the carbamoyl phosphate synthetase III, and for supplying ornithine
      required for citrulline synthesis intramitochondrially. Furthermore, the ammonia
      stress, due to exposure to high external ammonia, led to greater synthesis of
      urea-N probably as a consequence of induction of ureogenesis, as evidenced by a
      larger accumulation of urea-N in hepatocytes and higher secretion in culture
      media parallel to the increased concentration of ammonia-N in hepatocytes.
      Ammonia stress also led to specific coordinated patterns of induction of both the
      arg genes in isolated hepatocytes of walking catfish.

PMID- 28431971
TI  - Influence of stress associated with chronic alcohol exposure on drinking.
AB  - Stress is commonly regarded as an important trigger for relapse and a significant
      factor that promotes increased motivation to drink in some individuals. However,
      the relationship between stress and alcohol is complex, likely changing in form
      during the transition from early moderated alcohol use to more heavy uncontrolled
      alcohol intake. A growing body of evidence indicates that prolonged excessive
      alcohol consumption serves as a potent stressor, producing persistent
      dysregulation of brain reward and stress systems beyond normal homeostatic
      limits. This progressive dysfunctional (allostatic) state is characterized by
      changes in neuroendocrine and brain stress pathways that underlie expression of
      withdrawal symptoms that reflect a negative affective state (dysphoria, anxiety),
      as well as increased motivation to self-administer alcohol. This review
      highlights literature supportive of this theoretical framework for alcohol
      addiction. In particular, evidence for stress-related neural, physiological, and
      behavioral changes associated with chronic alcohol exposure and withdrawal
      experience is presented. Additionally, this review focuses on the effects of
      chronic alcohol-induced changes in several pro-stress neuropeptides
      (corticotropin-releasing factor, dynorphin) and anti-stress neuropeptide systems
      (nocicepton, neuropeptide Y, oxytocin) in contributing to the stress, negative
      emotional, and motivational consequences of chronic alcohol exposure. Studies
      involving use of animal models have significantly increased our understanding of
      the dynamic stress-related physiological mechanisms and psychological
      underpinnings of alcohol addiction. This, in turn, is crucial for developing new
      and more effective therapeutics for treating excessive, harmful drinking,
      particularly stress-enhanced alcohol consumption. This article is part of the
      Special Issue entitled "Alcoholism".

PMID- 28431975
TI  - Liposomal curcumin alters chemosensitivity of breast cancer cells to Adriamycin
      via regulating microRNA expression.
AB  - BACKGROUND: Emerging evidence suggests that curcumin can overcome drug resistance
      to classical chemotherapies, but poor bioavailability and low absorption have
      limited its clinical use and the mechanisms remain unclear. Also, Adriamycin
      (Adr) is one of the most active cytotoxic agents in breast cancer; however, the
      high resistant rate of Adr leads to a poor prognosis. METHODS: We utilized
      encapsulation in liposomes as a strategy to improve the bioavailability of
      curcumin and demonstrated that liposomal curcumin altered chemosensitivity of Adr
      resistant MCF-7 human breast cancer (MCF-7/Adr) by MTT assay. The miRNA and mRNA
      expression profiles of MCF-7/S, MCF-7/Adr and curcumin-treated MCF-7/Adr cells
      were analyzed by microarray and further confirmed by real-time PCR. We focused on
      differentially expressed miR-29b-1-5p to explore the involvement of miR-29b-1-5p
      in the resistance of Adr. Candidate genes of dysregulated miRNAs were identified
      by prediction algorithms based on gene expression profiles. Networks of KEGG
      pathways were organized by the selected dysregulated miRNAs. Moreover, protein
      protein interaction (PPI) was utilized to map protein interaction networks of
      curcumin regulated proteins. RESULTS: We first demonstrated liposomal curcumin
      could rescue part of Adriamycin resistance in breast cancer and further
      identified 67 differentially expressed microRNAs among MCF-7/S, MCF-7/Adr and
      curcumin-treated MCF-7/Adr. The results showed that lower expressed miR-29b-1-5p
      decreased the IC50 of MCF-7/Adr cells and higher expressed miR-29b-1-5p, weaken
      the effects of liposomal curcumin to Adr-resistance. Besides, we found that 20
      target genes (mRNAs) of each dysregulated miRNA were not only predicted by
      prediction algorithms, but also differentially expressed in the microarray. The
      results showed that MAPK, mTOR, PI3K-Akt, AMPK, TNF, Ras signaling pathways and
      several target genes such as PPARG, RRM2, SRSF1and EPAS1, may associate with drug
      resistance of breast cancer cells to Adr. CONCLUSIONS: We determined that an
      altered miRNA expression pattern is involved in acquiring resistance to Adr, and
      that liposomal curcumin could change the resistance to Adr through miRNA
      signaling pathways in breast cancer MCF-7 cells.

PMID- 28431976
TI  - The impact of exposure to environmental contaminant on hepatocellular lipid
      metabolism.
AB  - Increasing evidences show that ubiquitous perfluorooctanoic acid (PFOA), a
      representative environmental pollutant, is found to be linked to lipid
      dysmetabolism. However, the biological mechanism behind this outcome remains
      uninvestigated. In the present study, we established the PFOA-injured liver in
      mice to explore the underlying mechanism associated with PFOA-induced lipid
      disturbance in the liver via a group of biochemical and molecular assays. As
      results, PFOA-exposed mice showed increased transaminase (ALT), reduced
      triglyceride and free fatty acid contents in serum, as well as elevated level of
      hepatic triglyceride. Morphologically, PFOA-exposed mice displayed visible
      vacuolation in cytoplasm and abnormal cytoarchitecture in liver. In addition,
      PFOA-exposed liver showed up-regulated expressions of lipid-uptake associated
      mRNA of hepatic lipoprotein lipase (LPL) and fatty acid translocase (CD36) and
      down-regulated expression of lipid-uptake associated mRNA of apolipoprotein-B100
      (APOB). Moreover, validated data from immunohistochemistry and immunoblotting
      found that hepatocellular LPL and CD36 proteins were increased dose-dependently,
      and lowered expression of hepatic APOB was observed. In conclusion, our current
      findings reveal that PFOA-induced lipid dysmetabolism in the liver is involved to
      dysregulation of fatty acid trafficking.

PMID- 28431977
TI  - Transcriptome comparison reveals insights into muscle response to hypoxia in
      blunt snout bream (Megalobrama amblycephala).
AB  - The economic and biological significance of blunt snout bream (Megalobrama
      amblycephala) makes this species important to explore the underlying molecular
      mechanism of hypoxia response. In the present study, we compared the
      transcriptional responses to serious hypoxia in skeletal muscle among hypoxia
      tolerant (MT), sensitive (MS) and control (without hypoxia treatment, MC) M.
      amblycephala obtained according to the time difference of losing balance after
      hypoxia treatment. A total of 88,200,889 clean reads were generated and assembled
      into 44,493 unigenes. Transcriptomic comparison revealed 463 genes differentially
      expressed among different groups. A similar hypoxia-induced transcription
      patterns suggested a common hypoxia response involved in cell cycle, p53
      signaling pathway, apoptosis, heart contraction and blood circulation.
      Interesting, four genes, heat shock protein beta-8 (hspb8), cysteine/serine-rich
      nuclear protein 1 (csrnp1), salt-inducible kinase 1 (sik1), and visinin-like 1a
      (vsnl1a) were up-regulated in MT Vs MC but down-regulated in MS Vs MC.
      Additionally, FoxO signaling pathway was significantly enriched only in MT Vs MC.
      These results not only provided the first insights into the mechanism that muscle
      tissue coped with the hypoxia stress in cyprinid species, but offered a theory
      base for breeding of M. amblycephala with hypoxia-resistant traits.

PMID- 28431978
TI  - Temporal niche switching in Arabian oryx (Oryx leucoryx): Seasonal plasticity of
      24h activity patterns in a large desert mammal.
AB  - The Arabian oryx, a moderately large mammal that inhabits a harsh desert
      environment, has been shown to exhibit seasonal variations in activity and
      inactivity patterns. Here we analyzed the continuous year-round activity patterns
      of twelve free-roaming Arabian oryx under natural conditions from two varying
      desert environments in Saudi Arabia using abdominally implanted activity meters.
      We simultaneously recorded weather parameters at both sites to determine whether
      environmental factors are responsible for temporal niche switching as well as the
      seasonal structuring and timing of this behavioural plasticity. Our results
      demonstrate that Arabian oryx undergo temporal niche switching of 24h activity
      patterns at a seasonal level and exhibit distinct nocturnal/crepuscular activity
      during summer, diurnal activity during winter and intermittent patterns of
      behaviour during the transitional seasons of autumn and spring. In addition, the
      oryx exhibited inter- and intra-seasonal variations in the temporal budgeting of
      24h activity patterns. Strong relationships with both photoperiod and ambient
      temperatures were found and in some instances suggested that increasing ambient
      temperatures are a primary driving force behind seasonal shifts in activity
      patterns. These adaptive patterns may be dictated by the availability of food and
      water, which in turn are strongly influenced by seasonal climate variations.
      Overall, the adaptive responses of free-roaming Arabian oryx in such harsh and
      non-laboratorial conditions provide a framework for comparing wild populations as
      well as aiding conservation efforts.

PMID- 28431979
TI  - Past exposure to fruit and vegetable variety moderates the link between fungiform
      papillae density and current variety of FV consumed by children.
AB  - Higher fungiform papillae density (FPD) has been associated with lower taste
      sensitivity thresholds and greater perceived taste intensity along with
      consumption of fewer fruit and vegetables (FV). Children exposed to greater
      variety of FV tend to habitually consume more FV, however, it is unknown whether
      exposure effects are attenuated by individual differences in FPD or whether these
      effects vary according to sensory properties of FV. This study examined the links
      between children's FPD, current variety of FV consumed, and past experiences with
      variety of fruit and vegetables. FPD counts were obtained from 61 children
      between 5 and 9years old, in schools from affluent areas of Birmingham (UK).
      Parents completed food frequency questionnaires indicating the variety of FV
      consumed by children in the last 7days. Parents also indicated the number of
      different FV types the children had tasted in their lifetime. FV were subdivided
      to reflect differences in their sensory properties. The results showed that
      children with higher FPD who in their lifetime had tasted a greater variety of FV
      ate a larger variety of FV compared to children with higher FPD, but with lower
      past exposure. When examining effects within specific subcategories of fruits and
      vegetables, this pattern held for non-astringent fruit and showed a trend for non
      bitter vegetables. Children with lower FPD consumed similar variety of FV
      irrespective of past experiences with variety of FV. The results suggest that
      when strong or irritant sensory food properties are not a barrier to intake,
      higher FPD in the presence of supportive home food environment may be beneficial
      for FV intake. Individual phenotypic differences may affect responsiveness to
      environmental factors in children's intake of FV.

PMID- 28431980
TI  - Shear stress alterations in the celiac trunk of patients with a continuous-flow
      left ventricular assist device as shown by in-silico and in-vitro flow analyses.
AB  - BACKGROUND: The use of left ventricular assist devices (LVADs) to treat advanced
      cardiac heart failure is constantly increasing, although this device leads to
      high risk for gastrointestinal bleeding. METHODS: Using in-silico flow analysis,
      we quantified hemodynamic alterations due to continuous-flow LVAD (HeartWare,
      Inc., Framingham, MA) in the celiac trunk and major branches of the abdominal
      aorta, and then explored the relationship between wall shear stress (WSS) and
      celiac trunk orientation. To assess outflow from the aortic branch, a 3
      dimensional-printed patient-specific model of the celiac trunk reconstructed from
      an LVAD-supported patient was used to estimate echocardiographic outflow
      velocities under continuous-flow conditions, and then to calibrate computational
      simulations. Moreover, flow pattern and resulting WSS values were computed for 5
      patients with LVAD implantation. RESULTS: Peak WSS values were estimated on the 3
      branches of the celiac trunk and the LVAD cannula. The mean WSSs demonstrated
      that the left gastric artery underwent the highest WSS of 9.08 +/- 5.45 Pa, with
      an average flow velocity of 0.57 +/- 0.25 m/s compared with that of other vessel
      districts. The common hepatic artery had a less critical WSS of 4.58 +/- 1.77 Pa.
      A positive correlation was found between the celiac trunk angulation and the WSS
      stress just distal to the ostium of the celiac trunk (R = 0.9), which may
      increase vulnerability of this vessel to bleeding. CONCLUSIONS: Although further
      studies are needed to confirm these findings in a larger patient cohort,
      computational flow simulations may enhance the information of clinical image data
      and may have an application in clinical investigations of hemodynamic changes in
      LVAD-supported patients.

PMID- 28431982
TI  - Red blood cells and left ventricular assist devices-A lifespan under stress.

PMID- 28431981
TI  - Ventricular assist device elicits serum natural IgG that correlates with the
      development of primary graft dysfunction following heart transplantation.
AB  - BACKGROUND: Pre-transplant sensitization is a limiting factor in solid-organ
      transplantation. In heart transplants, ventricular assist device (VAD)
      implantation has been associated with sensitization to human leukocyte antigens
      (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously
      shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization
      in kidney allograft recipients. Here we assessed generation of Nabs after VAD
      implantation in pre-transplant sera and examined their contribution to cardiac
      allograft outcome. METHODS: IgM and IgG Nabs were tested in pre-transplant serum
      samples collected from 206 orthotopic heart transplant recipients, including 128
      patients with VAD (VAD patients) and 78 patients without VAD (no-VAD patients).
      Nabs were assessed by testing serum reactivity to apoptotic cells by flow
      cytometry and to the generic oxidized epitope, malondialdehyde, by enzyme-linked
      immunosorbent assay. RESULTS: No difference was observed in serum levels of IgM
      Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were
      significantly increased in VAD compared with no-VAD patients. This increase was
      likely due to the presence of the VAD, as revealed by lower serum IgG Nabs levels
      before implantation. Elevated pre-transplant IgG Nabs level was associated with
      development of primary graft dysfunction (PGD). CONCLUSIONS: Our study
      demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and
      oxidized epitopes. These findings further support broad and non-specific B-cell
      activation by VAD, resulting in IgG sensitization. Moreover, the association of
      serum IgG Nabs levels with development of PGD suggests a possible role for these
      antibodies in the inflammatory reaction accompanying this complication.

PMID- 28431983
TI  - Comparison of extracorporeal photopheresis and alemtuzumab for the treatment of
      chronic lung allograft dysfunction.
AB  - BACKGROUND: Survival after lung transplantation is limited by chronic lung
      allograft dysfunction (CLAD). Immunomodulatory therapies such as extracorporeal
      photopheresis (ECP) and alemtuzumab (AL) have been described for refractory CLAD,
      but comparative outcomes are not well defined. METHODS: We retrospectively
      reviewed spirometric values and clinical outcomes after therapy with ECP, AL, or
      no treatment (NT) in patients with CLAD who underwent transplant between January
      2005 and December 2014. We used inverse probability-weighted regression
      adjustment (IPWRA) to adjust for potential confounders affecting treatment
      choice. RESULTS: Of 267 patients, 31 received immunomodulatory therapies for
      CLAD, and 78 received NT. The slope of forced expiratory volume in 1 second
      (FEV1) decline significantly improved after treatment with AL and with ECP
      compared with pre-treatment FEV1 slope; however, there was no significant change
      in slope of forced vital capacity (FVC). Comparison with NT was limited because
      of clinical differences in treatment groups. After IPWRA, we found no significant
      difference in mean difference of FEV1 slope (ml/month) when comparing treatment
      with NT, suggesting stabilization of lung function in the treatment group. We
      found no difference between the 2 immunomodulatory therapies 1, 3, and 6 months
      post-treatment (-49.9 [95% CI -581.8, +482.0], p = 0.85; +27.7 [95% CI -167.6,
      +223.0], p = 0.78; -9.6 [95% CI -167.5, +148.2], p = 0.91). We found no
      difference in mean FVC slope or differences between ECP and AL in infection rates
      or survival after treatment. CONCLUSIONS: Immunomodulatory therapy for CLAD with
      ECP or AL was associated with a significant change in FEV1 slope post-treatment
      compared with pre-treatment slope, with minimal effect on FVC. There was no
      difference between the 2 therapies in their effect on pulmonary function.

PMID- 28431984
TI  - Thyroid disrupting pesticides impair the hypothalamic-pituitary-testicular axis
      of a wildlife bird, Amandava amandava.
AB  - The effect of two thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and
      imidacloprid (IMI) on the hypothalamic-pituitary-gonadal/testicular (HPG) axis of
      a seasonally breeding bird, Amandava amandava has been evaluated. Male birds
      (n=8/group) were exposed to each of the pesticide (0.25% LD50 of respective
      pesticide) as well as to their two equimixture doses (0.25% of LD50 of each and
      0.5% LD50 of each) through food for 30d during pre-breeding stage of the
      reproductive cycle. Reduction in weight, volume and other histopathological
      features revealed testicular regression. Suppression of gonadotropin releasing
      hormone, increased expression of gonadotropin inhibitory hormone in the
      hypothalamus of exposed groups as well as impairment of plasma levels of the
      reproduction related hormones indicated the disruption of the HPG axis. The
      pesticides interference of the thyroid function during the critical phase of
      reproductive development impaired the HPG axis; more significantly in co-exposed
      groups suggesting the cumulative toxicity.

PMID- 28431985
TI  - Quercetin interferes with the fluid volume and receptivity development of the
      uterus in rats during the peri-implantation period.
AB  - HYPOTHESIS: Quercetin could induce changes to the fluid volume and receptivity
      development of the uterus during peri-implantation period. METHODS: Female rats
      were treated with quercetin (10, 25 and 50mg/kg/day) subcutaneously beginning
      from day-1 pregnancy. Uterus was harvested at day-4 (following three days
      quercetin treatment) for morphological, ultra-structural, protein and mRNA
      expressional changes and plasma sex-steroid levels analyses. In another cohort of
      rats, implantation rate was determined at day-6 (following five days quercetin
      treatment). RESULTS: Administration of 50mg/kg/day quercetin causes increased in
      uterine fluid volume and CFTR expression but decreased in gamma-ENaC, AQP-5, AQP
      9 claudin-4, occludin, E-cadherin, integrin alphanbetaZE, FGF, Ihh and Msx
      1expression in the uterus. Pinopodes were poorly develop, tight junctions appear
      less complex and implantation rate decreased. Serum estradiol levels increased
      but serum progesterone levels decreased. CONCLUSIONS: Interference in the fluid
      volume and receptivity development of the uterus during peri-implantation period
      by quercetin could adversely affect embryo implantation.

PMID- 28431986
TI  - NINJ2- A novel regulator of endothelial inflammation and activation.
AB  - Previous genetic studies suggested that variants in NINJ2 (encode ninjurin2)
      confer risk to ischemic stroke or large artery atherosclerotic stroke. However,
      the underlying mechanisms of NINJ2 in ischemic stroke or atherosclerosis are
      still unknown. In this study, we hypothesized that NINJ2 may play a role in
      endothelial inflammation and activation, and regulate the process of
      atherosclerosis. Here, we demonstrated that NINJ2 can regulate the expression of
      a panel of genes that are associated with inflammation and atherosclerosis (e.g.
      IL-1beta, TNF-alpha, IL-8, IL-6, ICAM-1 and E-selectin) in human vascular
      endothelial cells (HUVECs). Moreover, we found the expression of ninjurin2 is
      upregulated in LPS stimulated HUVECs and mouse aorta, and it can regulate LPS
      induced endothelial activation and the adhesion of monocytes to endothelial
      cells. We also found that NINJ2 can regulate NF-kappaB and c-jun through
      interacting with TLR4. In conclusion, our study suggests that ninjurin2 is a
      novel regulator of endothelia inflammation and activation through TLR4 signaling
      pathways, and these data provided new insights into the mechanisms between NINJ2
      and atherosclerosis.

PMID- 28431987
TI  - Patterns of brain and cardiovascular activation while solving rule-discovery and
      rule-application numeric tasks.
AB  - It is known that solving mental tasks leads to tonic increase in cardiovascular
      activity. Our previous research showed that tasks involving rule application (RA)
      caused greater tonic increase in cardiovascular activity than tasks requiring
      rule discovery (RD). However, it is not clear what brain mechanisms are
      responsible for this difference. The aim of two experimental studies was to
      compare the patterns of brain and cardiovascular activity while both RD and the
      RA numeric tasks were being solved. The fMRI study revealed greater brain
      activation while solving RD tasks than while solving RA tasks. In particular, RD
      tasks evoked greater activation of the left inferior frontal gyrus and selected
      areas in the parietal, and temporal cortices, including the precuneus,
      supramarginal gyrus, angular gyrus, inferior parietal lobule, and the superior
      temporal gyrus, and the cingulate cortex. In addition, RA tasks caused larger
      increases in HR than RD tasks. The second study, carried out in a cardiovascular
      laboratory, showed greater increases in heart rate (HR), systolic blood pressure
      (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) while
      solving RA tasks than while solving RD tasks. The results support the hypothesis
      that RD and RA tasks involve different modes of information processing, but the
      neuronal mechanism responsible for the observed greater cardiovascular response
      to RA tasks than to RD tasks is not completely clear.

PMID- 28431988
TI  - Time trends in births and cesarean deliveries among women with disabilities.
AB  - BACKGROUND: Although it is likely that childbearing among women with disabilities
      is increasing, no empirical data have been published on changes over time in the
      numbers of women with disabilities giving birth. Further, while it is known that
      women with disabilities are at increased risk of cesarean delivery, temporal
      trends in cesarean deliveries among women with disabilities have not been
      examined. OBJECTIVE: To assess time trends in births by any mode and in primary
      cesarean deliveries among women with physical, sensory, or
      intellectual/developmental disabilities. METHODS: We conducted a retrospective
      cohort study using linked vital records and hospital discharge data from all
      deliveries in California, 2000-2010 (n = 4,605,061). We identified women with
      potential disabilities using ICD-9 codes. We used descriptive statistics and
      visualizations to examine time patterns. Logistic regression analyses assessed
      the association between disability and primary cesarean delivery, stratified by
      year. RESULTS: Among all women giving birth, the proportion with a disability
      increased from 0.27% in 2000 to 0.80% in 2010. Women with disabilities had
      significantly elevated odds of primary cesarean delivery in each year, but the
      magnitude of the odds ratio decreased over time from 2.60 (95% CI = 2.25 = 2.99)
      in 2000 to 1.66 (95% CI = 1.51-1.81) in 2010. CONCLUSION: Adequate clinician
      training is needed to address the perinatal care needs of the increasing numbers
      of women with disabilities giving birth. Continued efforts to understand cesarean
      delivery patterns and reasons for cesarean deliveries may help guide further
      reductions in proportions of cesarean deliveries among women with disabilities
      relative to women without disabilities.

PMID- 28431989
TI  - Live birth, miscarriage, and abortion among U.S. women with and without
      disabilities.
AB  - BACKGROUND: Prior studies have found that women with disabilities who give birth
      are more likely to have preterm deliveries and low birthweight infants. However,
      it is not known what proportion of pregnant women with disabilities experience
      live birth, versus miscarriage or abortion. OBJECTIVE: To compare proportions of
      live birth, miscarriage, and abortion among women with basic action difficulties,
      women with complex activity limitations, and women without disabilities in a
      nationally representative sample. METHODS: We analyzed pooled Medical Expenditure
      Panel Survey (MEPS) data from Panels 1-11 (covering years 1996-2007), which
      included a Pregnancy Detail module assessing outcomes for women who were pregnant
      during panel participation. We used chi-square tests and multivariable logistic
      regression to compare disability groups on pregnancy outcomes. RESULTS: Among
      women with a recorded pregnancy outcome, women with disabilities were less likely
      to have live births (80.8% of women with basic action difficulties and 75.3% of
      women with complex activity limitations versus 85.0% of women without
      disabilities), but differences related to disability were not significant when
      adjusting for covariates. Women with complex activity limitations were
      significantly more likely to report miscarriages, even when controlling for
      covariates. Disability was not significantly associated with abortion in the
      adjusted analysis. CONCLUSIONS: Our findings add to the growing literature on
      pregnancy outcomes among women with disabilities, providing important information
      about outcomes that are not reflected in delivery records. We found few
      differences between women with and without disabilities, and good likelihood of
      live birth among women with disabilities experiencing pregnancy.

PMID- 28431990
TI  - A common polymorphism decreases LRP1 mRNA stability and is associated with
      increased plasma factor VIII levels.
AB  - The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated
      with increased levels of plasma factor VIII (FVIII). We aimed to explore eight
      functional genetic LRP1 variants for their potential roles in regulating FVIII
      levels and acute ischemic stroke (AIS). This genetic association study enrolled
      192 patients with AIS and 134 controls. There were no significant differences in
      the genetic frequency of the eight functional single-nucleotide polymorphisms
      (SNPs) between the control and AIS groups. However, while analyzing the
      association between the eight SNPs and plasma FVIII levels, subjects with T/T
      genotype of rs1800137 (vs. CC+CT) were found to be associated with higher FVIII
      levels (23.5IU/dL; 95% confidence interval, 7.4-39.5IU/dL; P=0.0044) after
      adjusting for age, gender, estimated glomerular filtration rate, O blood type,
      inflammatory state, and body mass index. An analysis of the mRNA stability and
      abundance was designed and performed using minigene system transfected into HepG2
      cells to assess the possible differences in mRNA stabilities between rs1800137 CC
      (rs1800137C) and TT (rs1800137T) genotypes. Site-directed mutagenesis revealed
      that rs1800137T accounts for the observed decrease in mRNA stability. The SNP
      rs1800137, located in exon 8, has been identified as an exon-splicing enhancer in
      silico. However, alternative splicing of LRP1 without inclusion of exon 8 was not
      identified. In transfected HepG2 cells, cycloheximide slowed down the degradation
      of the rs1800137T-containing minigene. These results demonstrate that synonymous
      SNP rs1800137 can lead to increased plasma FVIII levels due to decreased mRNA
      stability via translation-dependent mRNA degradation associated with codon
      optimality.

PMID- 28431991
TI  - Molecular mechanisms of trauma-induced acute kidney injury: Inflammatory and
      metabolic insights from animal models.
AB  - Trauma-induced acute kidney injury (AKI), such as after hemorrhagic shock (HS) or
      burn, remains a significant problem in the intensive care unit and is associated
      with increased mortality. The pathophysiology that drives AKI post-trauma is
      multi-factorial, and includes both inflammatory and metabolic alterations.
      Identifying the systemic profile that contributes to AKI is crucial not only for
      early diagnosis, but also for identifying treatments that improve kidney function
      and maintaining long-term patient health. In an effort to elucidate this
      molecular pathophysiology researchers have utilized a variety of animal models
      including chemically-induced (i.e., cisplatin), blocking renal perfusion (i.e.,
      arterial clamping) and inducing burn or HS. As the latter burn and HS models are
      unequivocally applicable to studying AKI in the context of traumatic injury, this
      review will summarize the inflammatory and metabolic insights associated with AKI
      gained with these animal models. Moreover, novel therapeutic strategies brought
      forth with these models will be discussed.

PMID- 28431992
TI  - Genomic answers for recurrent spontaneous abortion in Saudi Arabia: An array
      comparative genomic hybridization approach.
AB  - To study the genomics/genetic factors associated with recurrent spontaneous
      abortion (RSA), as ~50% of RSA are unexplained. However, chromosome abnormalities
      have been reported to play major role in RSA. We performed whole genome array-CGH
      based genomic analysis of forty four Saudi RSA patients to identify potential
      molecular and chromosomal abnormalities. We identified a total of 845
      alterations, usually not detected by classic cytogenetic methods, in different
      genomic regions using a cut off value of -0.25 and 0.25 for structural loss and
      gain, whereas -1.0 and 0.58 were used for single copy number deletion and
      duplication respectively. We identified frequent (present at least in 10% of
      patients) alterations including three macro-alteration at 8p23.1, 10q11.21-q11.22
      and 15q11.2 as well as large numbers of micro-deletions/amplifications with
      affected genes including 22q11.23 (GSTT1), 3p22.2 (CTDSPL), 6p21.32 (HLA), and
      8p22 (MSR1). Pathway analysis of genes located in detected CNVs regions revealed
      the allograft rejection signaling, IL-4 signaling, and autoimmune thyroid disease
      signaling as the most significant canonical pathways associated with RSA. Whole
      genome array CGH technique can be used to identify potential genes, biofunctions
      and chromosomal abnormalities associated with RSA which is supported by our
      findings of a number of novel CNVs/genes (22q11.23/GSTT1, 3p22.2/CTDSPL,
      6p21.32/HLA, 8p22/MSR1, and 14q32.33/AKT1) and pathways in patients affected with
      RSA. To improve diagnosis and treatment of RSA, a comprehensive procedure is
      needed for identification and validation of causative genes.

PMID- 28431993
TI  - Re-examining Prostate-specific Antigen (PSA) Density: Defining the Optimal PSA
      Range and Patients for Using PSA Density to Predict Prostate Cancer Using
      Extended Template Biopsy.
AB  - OBJECTIVE: To compare the predictive accuracy of prostate-specific antigen (PSA)
      density vs PSA across different PSA ranges and by prior biopsy status in a
      prospective cohort undergoing prostate biopsy. MATERIALS AND METHODS: Men from a
      prospective trial underwent an extended template biopsy to evaluate for prostate
      cancer at 26 sites throughout the United States. The area under the receiver
      operating curve assessed the predictive accuracy of PSA density vs PSA across 3
      PSA ranges (<4 ng/mL, 4-10 ng/mL, >10 ng/mL). We also investigated the effect of
      varying the PSA density cutoffs on the detection of cancer and assessed the
      performance of PSA density vs PSA in men with or without a prior negative biopsy.
      RESULTS: Among 1290 patients, 585 (45%) and 284 (22%) men had prostate cancer and
      significant prostate cancer, respectively. PSA density performed better than PSA
      in detecting any prostate cancer within a PSA of 4-10 ng/mL (area under the
      receiver operating characteristic curve [AUC]: 0.70 vs 0.53, P < .0001) and
      within a PSA >10 mg/mL (AUC: 0.84 vs 0.65, P < .0001). PSA density was
      significantly more predictive than PSA in detecting any prostate cancer in men
      without (AUC: 0.73 vs 0.67, P < .0001) and with (AUC: 0.69 vs 0.55, P < .0001) a
      previous biopsy; however, the incremental difference in AUC was higher among men
      with a previous negative biopsy. Similar inferences were seen for significant
      cancer across all analyses. CONCLUSION: As PSA increases, PSA density becomes a
      better marker for predicting prostate cancer compared with PSA alone.
      Additionally, PSA density performed better than PSA in men with a prior negative
      biopsy.

PMID- 28431994
TI  - Raynaud's Phenomenon: Revisiting a Rare Sign of Pheochromocytoma and
      Paraganglioma.
AB  - Paraganglioma (PGL) are rare tumors arising from extra-adrenal chromaffin cells
      and occasionally secret catecholamines. The patient commonly presents with
      headache, palpitation, anxiety, diaphoresis, and episodic or sustained
      hypertension. Rarely patient can present with Raynaud's phenomenon. We present a
      case of adolescent girl who presented with isolated Raynaud's phenomenon as only
      manifestation of metastasis of PGL 3 years after undergoing surgical excision of
      normetanephrine secreting abdominal PGL.

PMID- 28431995
TI  - Robot-assisted Laparoscopic Urachal Excision in Children.
AB  - OBJECTIVE: To report the first exclusively pediatric series of robot-assisted
      urachal remnant excisions in children. METHODS: We reviewed the medical records
      of all children who underwent robot-assisted excision of urachal remnants from
      2010 to 2016. For the procedure, a 3-port approach was performed in all cases.
      Excision of the urachus was performed, along with partial cystectomy if there was
      clear or suspected bladder involvement. Outcomes and complications were reviewed.
      RESULTS: Sixteen cases of robotic urachal excision were performed during the
      study period in patients aged 0.8-16.5 years. Complete excision was accomplished
      in all cases with no conversions. Partial cystectomy was performed in 11 cases,
      in which a urinary catheter was left for 1 day in all cases (no catheter was left
      in the absence of partial cystectomy). The only complication was a bladder leak
      requiring open surgical repair. There were no bowel injuries or hernias. The
      median operative time was 107 minutes. The length of stay was 2 days with partial
      cystectomy and 1 day without partial cystectomy. All patients were well at follow
      up. CONCLUSION: We report the largest known series of robot-assisted urachal
      remnant excisions in children, demonstrating this minimally invasive approach to
      be safe and effective.

PMID- 28431996
TI  - Comparison of Silodosin Monotherapy vs Silodosin With Tadalafil Add-on Therapy in
      Patients With Benign Prostatic Hyperplasia.
AB  - OBJECTIVE: To evaluate the efficacy and safety of add-on therapy with the
      phosphodiesterase type 5 inhibitor tadalafil for patients with lower urinary
      tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) treated with
      the alpha1-adrenoceptor blocker silodosin. MATERIALS AND METHODS: We analyzed 103
      patients with LUTS/BPH with an International Prostate Symptom Score (IPSS) of >8
      after >=4 weeks of silodosin treatment from April 2016 through December 2016 at
      Kori Hospital. The patients subsequently received silodosin 4.0 mg twice daily
      (monotherapy group) or silodosin 4.0 mg twice daily plus tadalafil 5.0 mg once
      daily (add-on therapy group) for 8 weeks. We assessed adverse events and
      evaluated the mean change from baseline to 8 weeks in the IPSS, Overactive
      Bladder Symptom Score (OABSS), maximum urine flow rate (Qmax), and post-void
      residual urine volume. RESULTS: Of 103 patients, 101 (98.1%) could continue
      medical treatment. The IPSS, OABSS, and Qmax showed significantly greater
      improvement in the add-on therapy than in the monotherapy group (-3.92 vs -1.24, 
      1.18 vs 0.10, and 1.09 vs -1.04, respectively; all P <.05). Although 4 patients
      experienced adverse events (add-on therapy: n = 3, 5.7%; monotherapy: n = 1,
      2.0%), no significant differences were observed (P = .62). Among patients with
      overactive bladder (n = 55), the IPSS storage symptom subscore, IPSS urgency
      subscore, and OABSS urgency subscore showed significantly greater improvement in
      the add-on therapy than in the monotherapy group (-2.23 vs 0.17, -0.88 vs 0.28,
      and -1.5 vs -0.48, respectively; all P <.05). CONCLUSION: Add-on therapy with
      tadalafil may be effective for patients with LUTS/BPH resistant to silodosin
      monotherapy.

PMID- 28431997
TI  - ?

PMID- 28431998
TI  - European College of Orthodontics: Commission of affiliation and titularization.
AB  - : Date of birth: 12/10/1987; sex: female. A. PRETREATMENT RECORDS: 24 years 8
      months; 16/06/2011. DIAGNOSIS: Skeletal and dental Class I, maxillary
      endognathia, anterior vertical excess with open bite; teeth missing prior to
      treatment: 18, 28, 38, 48. TREATMENT PLAN: Appliances and devices: single-stage
      surgical-orthodontic treatment using pretorqued and preangled bimaxillary
      multibracket appliances with 0.022*0.028" archwire, along with an expander during
      the surgical phase and then a transpalatal arch to stabilize the transverse
      correction. START OF TREATMENT: 24 years 8 months; 16/06/2011. B. POSTTREATMENT
      RECORDS: 26/10/2012; 26 years. RETENTION: Maxillary: bonded wire from 13 to 23
      and slip-cover retainer; 29/01/2013; mandibular: bonded wire from 33 to 43;
      29/01/2013. C. POST-RETENTION RECORDS (1 YEAR MINIMUM): 14/12/2013; 27 years;
      date of end of retention: 14/12/2013: maxillary: bonded wire from 13 to 23;
      mandibular: bonded wire from 33 to 43; duration of retention: 12 months.

PMID- 28431999
TI  - Novel method to rapidly and efficiently lyse Escherichia coli for the isolation
      of recombinant protein.
AB  - Rapid and high-throughput protein purification methods are required to explore
      structure and function of several uncharacterized proteins. Isolation of
      recombinant protein expressed in Escherichia coli strain BL21 (DE3) depends
      largely on the efficient and speedy bacterial cell lysis, which is considered as
      the bottleneck during protein purification. Cells are usually lysed by either
      sonication or high pressure homogenization, both of which are slow, require
      special equipment, lead to heat generation, and may result in loss of protein's
      biological activity. We report here a novel method to lyse E. coli, which is
      rapid, and results in high yield of isolated protein. Here, we have carried out
      intracellular expression of lysozyme domain (LD) of mycobacteriophage D29
      endolysin. LD remains non-toxic until chloroform is added into the culture medium
      that permeabilizes bacterial cell membrane and allows the diffusion of LD to the
      peptidoglycan layer causing latter's degradation ensuing cell lysis. Our method
      efficiently lyses E. coli in short duration. As a proof-of-concept, we
      demonstrate large scale isolation and purification of alpha subunit of E. coli
      RNA polymerase and GFP, when they are co-expressed with LD. We believe that our
      method will be adopted easily in high-throughput as well as large scale protein
      isolation experiments.

PMID- 28432000
TI  - Determination of thiol-to-protein ratio and drug-to-antibody ratio by in-line
      size exclusion chromatography with post-column reaction.
AB  - An in-line size-exclusion (SE) ultra-high-performance liquid chromatography
      (UHPLC)- 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) method to quantify thiols in
      monoclonal antibodies (mAb) when manufacturing antibody-drug conjugates (ADCs)
      was developed. The mAbs are separated on an SE-UHPLC column and monitored with a
      UV detector at a wavelength of 280 nm. Eluents are channeled into a reaction coil
      and mixed with DTNB to form 5-thio-2-nitrobenzoic acid (TNB). Thiol concentration
      is calculated using absorption at 412 nm. Using optimized conditions, partially
      reduced mAbs can be separated from low-molecular weight contaminants and undergo
      the DTNB reaction. The standard curve of L-cysteine had good linearity between
      100 and 1000 MUM. The selectivity, linearity, repeatability, and robustness of
      this method were evaluated. The calculated free-SH:protein ratios of partially
      reduced mAbs were consistent between in-line SE-UHPLC-DTNB and conventional
      methods. The SE-UHPLC-DTNB method showed time- and temperature-dependent changes
      in the free-SH:protein ratio of mAbs during reduction. The changes in drug
      antibody ratio (DAR) of ADCs during the conjugation reaction were also evaluated.
      This method is an inexpensive and versatile alternative to conventional methods
      of estimating the free-SH:protein ratio of mAbs and the DAR of ADCs. This method
      also minimizes assay time.

PMID- 28432001
TI  - In vivo and in vitro study of osteogenic potency of endothelin-1 on bone marrow
      derived mesenchymal stem cells.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) are a major source of
      osteoblasts and are crucial for bone remolding and repair and thus they are
      widely used for tissue engineering applications. Tissue engineering in
      combination with gene therapy is considered as a promising approach in new bone
      regeneration. Endothelin-1(EDN-1)is produced by vascular endothelial cells which
      plays an important role during bone development. However, its role in BMSCs
      remains largely unknown. We established EDN-1 overexpressed BMSCs, proliferation
      ability and osteogenesis differentiation were detected respectively. Transduced
      BMSCs were then combined with CPC-scaffold to repair calvarial defects in rats to
      evaluate the in-vivo osteogenic potential of EDN-1. EDN-1 overexpressed BMSCs
      showed increased proliferation and significantly increased osteogenesis potential
      ability than vector transfected control. The in-vivo data also revealed more new
      bone formation with higher bone mineral density and number of trabeculae in EDN-1
      overexpressed BMSCs. These findings have demonstrated the influence of EDN-1 on
      differentiation potential of BMSCs, which suggest that EDN-1 may be a new
      promising agent for bone tissue engineering.

PMID- 28432002
TI  - miR-429 inhibits metastasis by targeting KIAA0101 in Soft Tissue Sarcoma.
AB  - Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors with high
      metastatic potential. There being only a handful of publication on metastasis of
      STS, we investigated the miRNA mediated target gene regulations in modulating the
      metastatic processes in this cancer. In this study, we amalgamated gene and miRNA
      expression profiles of high-grade STS samples with miRNA target predictions and
      identified miR-429 targeting KIAA0101 as a novel pair, which remain unexplored in
      STS metastasis. We validated their expression in metastatic fibrosarcoma cell
      line, HT1080 and performed several functional assays using miRNA mimics and
      KIAA0101 over-expression vector to confirm their role in metastasis. We observed
      miR-429 is downregulated in HT1080 cells and acting as an anti-metastatic miRNA
      that inhibited proliferation, migration, anchorage independent growth and
      invasion by de-repressing KIAA0101. Moreover, the renilla luciferase reporter
      assay confirmed that miR-429 targets KIAA0101 by binding to its 3/UTR and
      influence its expression. Taken together, our work demonstrated miR-429 mediates
      deregulation of KIAA0101 by acting as an anti-metastatic miRNA that targets
      KIAA0101 pro-metastatic gene during metastasis of STS.

PMID- 28432003
TI  - The effectiveness of super-selective injection with anchor balloon technique for
      collateral channel assessment.
AB  - The careful assessment of collateral channels is important for a retrograde
      approach for a chronic total coronary occlusion (CTO). This case report describes
      a percutaneous coronary intervention for CTO of the distal right coronary artery
      with good collateral circulation. All visible collateral channels failed by the
      retrograde approach; however, the procedure was successful using the distal
      atrial circumflex (AC) channel. Although this distal channel was poorly
      visualized on standard coronary angiography, it was clearly contrasted
      retrogradely from the CTO exit using a super-selective injection through the
      proximal AC channel as the antegrade flow was obstructed by the anchor balloon.
      This case highlights a unique super-selective injection with anchor balloon
      technique for collateral channel assessment.

PMID- 28432004
TI  - Impact of right ventricular side branch occlusion during percutaneous coronary
      intervention of chronic total occlusions on right ventricular function.
AB  - OBJECTIVE: To determine the impact of right ventricular side branch (RVB)
      occlusion, during percutaneous coronary interventions (PCIs) of chronic total
      occlusions (CTOs) of the right coronary artery (RCA), on right ventricular (RV)
      function. BACKGROUND: Developments in PCI techniques have expanded PCI CTO
      feasibility. However, the utilization of dissection and reentry techniques and
      extensive stent implantation increases the risk of coronary side branch
      occlusion. METHODS: Fifty-four patients (80% male, 63+/-10years) evaluated with
      cardiac magnetic resonance imaging (CMR) prior and three months after successful
      PCI CTO RCA (median: 99days, IQR: 92-105days) were included. Right ventricular
      end-diastolic volume (RVEDV), end-systolic volume (RVESV), and ejection fraction
      (RVEF) were quantified on CMR images. Occurrence of RVB occlusion and/or RVB
      recruitment was assessed using procedural angiograms. RESULTS: RVB occlusion was
      observed in 12 patients (22%), while RVB recruitment occurred in seven patients
      (13%). Overall, RVEF was comparable between baseline and follow-up (53.8+/-5.8
      vs. 53.9+/-5.8%, p=0.95). RVB occlusion was not associated with a significant
      change in RVEDV or RVEF (156.9+/-36.3 vs. 162.1+/-35.5mL, p=0.30 and 54.2+/-3.9
      vs. 52.7+/-4.4%, p=0.19, respectively); however a trend was observed for an
      increase of RVESV (72.5+/-20.0 vs. 77.4+/-20.7mL, p=0.05) at follow-up. RVB
      recruitment did not result in a significant improvement of RVEF (55.4+/-4.6 vs.
      56.1+/-5.3%, p=0.75). CONCLUSION: RVB occlusion was not associated with a
      significant decreased RVEF at follow-up, although the results suggested a limited
      increase of RVESV.

PMID- 28432005
TI  - Radial/Ulnar angioplasty in selected patients undergoing elective angiography or
      PCI using complex forearm approach.
AB  - BACKGROUND: Angioplasty on the radial artery have been performed with good
      success rates in patients with critical hand ischemia. We sought to assess the
      feasibility and safety of radial angioplasty on complex radial access in patients
      undergoing coronary angiography. METHODS/MATERIAL: A prospective series of
      procedures with complex radial/ulnar access to which radial-ulnar angioplasty (RU
      A) was performed. We set goals of efficacy and safety that included the success
      rate of the procedure (need for Crossover femoral) and the existence of radial
      pulse at one month. RESULTS: 18 cases of RU-A out of 11,500 procedures from March
      2010 to July 2016 (0.15%) were included. The majority of the patients were men
      with a variety of cardiovascular risk factors (age 71+/-9; 94% Hypertensive, 56%
      Diabetic, 18% chronic kidney disease). The most common indication for
      radial/ulnar angioplasty was severe arteriosclerotic stenosis. Angioplasty was
      performed with different types of over the wire peripheral balloons (Mean
      diameter 4,3+/-1 and mean length 42+/-15mm), in one case a stent implantation was
      needed. The success rate was 100% without vascular complications at 1-month
      clinical and vascular doppler follow-up. CONCLUSIONS: Radial/ulnar artery
      angioplasty is feasible and safe in selected patients undergoing elective
      angiography or percutaneous coronary intervention using complex forearm approach.

PMID- 28432006
TI  - Stepwise use of circulatory support devices in a patient refractory to
      cardiopulmonary resuscitation.
AB  - This case describes the management of a patient admitted to an emergency
      department with general malaise, who deteriorated into cardiac arrest and
      refractory to advanced life support measures. After extracorporeal
      cardiopulmonary resuscitation (eCPR) with veno-arterial extracorporeal membrane
      oxygenation in association with an Impella 2.5 device, the patient underwent
      cardiac surgery (tissue aortic valve replacement, coronary artery bypass grafting
      and implantation of short-term paracorporeal left ventricular assist device).
      Subsequently a long-term LVAD was implanted and the patient was successfully
      discharged shortly afterwards. This report illustrates the challenges of
      'clinical decision making' in a complex patient utilising a wide range of left
      ventricular support mechanical devices with varying degrees of invasiveness,
      whilst also reflecting on the current financial and economic considerations in
      utilizing this type of care pathway.

PMID- 28432007
TI  - Caloric compensation in preschool children: Relationships with body mass and
      differences by food category.
AB  - Maintaining a healthy weight may involve compensating for previously consumed
      calories at subsequent meals. To test whether heavier children demonstrated
      poorer caloric compensation across a range of conditions, and to explore whether
      compensation failure was the result of inadequate adjustment of overall intake or
      specific over-consumption of highly palatable, high energy-density 'junk' foods,
      we administered two compensation tests to a sample of 4-5 y olds. For Test A,
      preloads varied only in carbohydrate content and were organoleptically
      indistinguishable (200 ml orange-flavored beverage [0 kcal vs. 200 kcal]). For
      Test B, the preloads varied substantially in both macronutrient composition and
      learned gustatory cues to caloric content (200 ml water [0 kcal] vs. 200 ml
      strawberry milkshake [200 kcal]). Each preload was followed 30 min later by a
      multi-item ad-libitum meal containing junk foods (chocolate cookies, cheese
      flavored crackers) and core foods (fruits and vegetables, bread rolls, protein
      foods). Testing took place at the children's own school under normal lunch-time
      conditions. Children were weighed and measured. Caloric compensation occurred in
      both tests, in terms of total, junk and core food intake (RMANOVA, all p < 0.01).
      Higher BMI z scores were associated with greater average caloric compensation (r
      = -0.26; p < 0.05), such that overweight/obese children showed least compensation
      (41%), children over the 50th centile the next least (59%), and children under
      the 50th centile (80%) the most. For Test A only, obese/overweight children
      compensated less well than normal-weight children in terms of junk food intake
      (RMANOVA preload-by-weight group interaction p < 0.05), with no significant
      effect for core foods. Our results suggest that caloric compensation is
      consistently poorer in heavier children, and that overweight/obese children's
      preferences for junk foods may overwhelm intake regulation mechanisms within
      meals containing those foods.

PMID- 28432008
TI  - Turkish version of the Intuitive Eating Scale-2: Validity and reliability among
      university students.
AB  - Intuitive Eating is defined as "the dynamic process-integrating attunement of
      mind, body, and food". The purpose of this study was, therefore, adapt the IES-2
      to the Turkish language and reliability and validity of IES-2 among Turkish
      populations. We also examined the instrument's internal consistency and test
      retest reliability and analysed the relationships between the IES-2 and several
      variables so as to evaluate the convergent and discriminant validity. Three
      hundred seventy-seven undergraduate and postgraduate women and men between the
      ages of 19-31 years (mean 22.3, SD = 3.53) attending two large private
      universities in Istanbul, Turkey. The best solution from the principal factors
      analysis of the 23 items of the IES-2 revealed four factors corresponding to the
      four subscales (F1: Eating for physical rather than emotional reasons; F2:
      Unconditional permission to eat; F3: Reliance on hunger and satiety cues; F4:
      Body-food choice congruence), as reported by the authors of the questionnaire.
      Bartlett's test of sphericity gave X2 = 9043.49 (p < 0.001), while the Kaiser
      Meyer-Olkin index was 0.87 (KMO were 0.89 for women and 0.83 for men). The test
      retest reliability of the IES-2 was 0.88 for the IES-2 total score. The IES-2 had
      a = 0.82. These findings support the notion that intuitive eating is a viable
      concept for university students and the IES can be used to examine adaptive
      eating behaviors in this population.

PMID- 28432009
TI  - The lateral hypothalamus to lateral habenula projection, but not the ventral
      pallidum to lateral habenula projection, regulates voluntary ethanol consumption.
AB  - The lateral habenula (LHb) is an epithalamic brain region implicated in aversive
      processing via negative modulation of midbrain dopamine (DA) and serotonin (5-HT)
      systems. Given the role of the LHb in inhibiting DA and 5-HT systems, it is
      thought to be involved in various psychiatric pathologies, including drug
      addiction. In support, it has been shown that LHb plays a critical role in
      cocaine- and ethanol-related behaviors, most likely by mediating drug-induced
      aversive conditioning. In our previous work, we showed that LHb lesions increased
      voluntary ethanol consumption and operant ethanol self-administration and blocked
      yohimbine-induced reinstatement of ethanol self-administration. LHb lesions also
      attenuated ethanol-induced conditioned taste aversion suggesting that a mechanism
      for the increased intake of ethanol may be reduced aversion learning. However,
      whether afferents to the LHb are required for mediating effects of the LHb on
      these behaviors remained to be investigated. Our present results show that
      lesioning the fiber bundle carrying afferent inputs to the LHb, the stria
      medullaris (SM), increases voluntary ethanol consumption, suggesting that
      afferent structures projecting to the LHb are important for mediating ethanol
      directed behaviors. We then chose two afferent structures as the focus of our
      investigation. We specifically studied the role of the inputs from the lateral
      hypothalamus (LH) and ventral pallidum (VP) to the LHb in ethanol-directed
      behaviors. Our results show that the LH-LHb projection is necessary for
      regulating voluntary ethanol consumption. These results are an important first
      step towards understanding the functional role of afferents to LHb with regard to
      ethanol consumption.

PMID- 28432010
TI  - Exposure to an enriched environment facilitates motor recovery and prevents short
      term memory impairment and reduction of striatal BDNF in a progressive
      pharmacological model of parkinsonism in mice.
AB  - Previous studies showed that the repeated administration with a low dose of
      reserpine (RES) induces a gradual appearance of motor signs and cognitive
      deficits compatible with parkinsonism in rodents. Environmental stimulation has
      neuroprotective effects in animal models of neurodegenerative damage, including
      acutely induced parkinsonism. We investigated the effects of exposure to an
      enriched environment (EE) on motor, cognitive and neuronal (levels of tyrosine
      hydroxylase, TH and brain derived neurotrophic factor, BDNF) deficits induced by
      a progressive model of Parkinson's disease (PD) in mice. Male mice were
      repeatedly treated with vehicle or 0.1mg/kg of RES (s.c) and kept under two
      housing conditions: standard environment (SE) and EE. In animals kept in SE, the
      treatment with RES induced deficits in motor function (catalepsy test, open field
      and oral movements), in novel object recognition (NOR) and plus-maze
      discriminative avoidance tasks. The environmental stimulation facilitated the
      recovery of motor deficits assessed by the catalepsy test after the end of
      treatment. Additionally, exposure to EE prevented the memory deficit in the NOR
      task. Treatment with RES induced a reduction in the number of TH positive cells
      in SNpc and VTA, which recovered 30days after the end of treatment. Finally, RES
      reduced the levels of BDNF in the striatum and the exposure to the EE prevented
      this effect. These results suggest that plastic brain changes induced by EE
      promote beneficial effects on the progression of neuronal impairment related to
      PD.

PMID- 28432011
TI  - What is an affordance? 40 years later.
AB  - About 40 years ago, James J. Gibson coined the term "affordance" to describe the
      action possibilities offered to an animal by the environment with reference to
      the animal's action capabilities. Since then, this notion has acquired a
      multitude of meanings, generating confusion in the literature. Here, we offer a
      clear operationalization of the concept of affordances and related concepts in
      the field of tool use. Our operationalization is organized around the distinction
      between the physical (what is objectively observable) and neurocognitive (what is
      subjectively experienced) levels. This leads us to propose that motor control
      (dorso-dorsal system), mechanical knowledge (ventro-dorsal system) and function
      knowledge (ventral system) could be neurocognitive systems respectively involved
      in the perception of affordances, the understanding of mechanical actions and the
      storage of contextual relationships (three action-system model; 3AS). We end by
      turning to two key issues that can be addressed within 3AS. These issues concern
      the link between affordances and tool incorporation, and the constraints posed by
      affordances for tool use.

PMID- 28432012
TI  - Novel compound heterozygous mutations in the PEX1 gene in two Chinese newborns
      with Zellweger syndrome based on whole exome sequencing.
AB  - Peroxisome biogenesis disorders (PBDs) represent a spectrum of human genetic
      disorders that are characterized by damaged peroxisome assembly. In the newborn
      period, the characteristics of affected patients include dysmorphic facial
      features, neonatal hypotonia, seizures, ocular abnormalities, poor feeding, liver
      cysts with hepatic dysfunction and skeletal defects. These can be caused by a
      defect in at least 14 different PEX genes. In this study, whole-exome sequencing
      (WES) was performed on samples from two Chinese newborns with clinical features
      of Zellweger syndrome. WES identified two novel mutations (c.2416+1G>T and
      c.2489delT) in patient 1 and another two novel mutations (c.1483+1G>A and
      c.1727dupG) in patient 2 in the PEX1 gene. All four mutations have a serious
      influence on the protein function, which also highlights the power of WES,
      particularly in clinically challenging cases.

PMID- 28432013
TI  - Design of multielectrode arrays for uniform sampling of different orientations of
      tuned unit populations in the cat visual cortex.
AB  - For better reconstruction of stimulus orientation from a single trial activity of
      the neuron population in the visual cortex, we need uniform samplings of
      differently oriented tuned neurons. We recorded multiple neurons simultaneously
      by using either a four-tetrode array or an eight-microelectrode array, and
      examined what kinds of electrodes and layouts provided a more homogeneous
      distribution of the units' optimal orientations. The unit population sampled by a
      four-tetrode array showed more homogeneous distribution than those sampled by an
      eight-microelectrode array. We confirmed this property by simulated recording
      sessions based on the optical imaging data of the orientation map.

PMID- 28432015
TI  - BLaTM 2.0, a Genetic Tool Revealing Preferred Antiparallel Interaction of
      Transmembrane Helix 4 of the Dual-Topology Protein EmrE.
AB  - Parallel and antiparallel transmembrane helix-helix interactions support the
      folding and non-covalent assembly of many integral membrane proteins. While
      several genetic tools are currently in use to study parallel transmembrane helix
      helix interactions, antiparallel associations have been difficult to determine.
      Here, we present a novel genetic approach, termed BLaTM 2.0, which can be used in
      combination with the recently presented BLaTM 1.2 to compare the efficiency of
      antiparallel and parallel transmembrane domain (TMD) interactions in a natural
      membrane. In a practical application of the BLaTM system, we find that the
      antiparallel interaction of TMD4, the known dimerization domain of the dual
      topology small multidrug transporter EmrE, is sequence-specific and much stronger
      than the parallel one. This suggests that TMD4 has evolved to favor the formation
      of dual-topology EmrE dimers over single-topology dimers.

PMID- 28432017
TI  - Dual-functional nanoparticles for precise drug delivery to Alzheimer's disease
      lesions: Targeting mechanisms, pharmacodynamics and safety.
AB  - Alzheimer's disease (AD) is the most common form of dementia and is characterized
      by the cerebral accumulation of extracellular amyloid plaques. In a previous
      study, this histopathological hallmark was used as a target on a dual-functional
      nanoparticle (TQNP) to deliver biotechnological drugs, such as the H102 peptide,
      a beta-sheet breaker, to AD lesions precisely. This delivery system could reduce
      the amyloid-beta (Abeta) burden in the brains of AD model mice, as well as
      ameliorated the memory impairment of the mice. Regretfully, the mechanism how
      nanoparticles penetrated the BBB and subsequently targeted to the plaques is
      still unclear. In this study, the internalization, subcellular fate and
      transportation of the nanoparticles on bEnd.3 cells and an in vitro BBB model,
      demonstrated that TQNP could be taken up through various routes, including
      caveolae-mediated endocytosis, suggesting that some of TQNP were able to cross
      the BBB intact. Then, the TQNP were visualized to specifically bind to the Abeta
      plaques. TQNP targeting to amyloid plaques might lead to enhanced therapeutic
      efficacy, which was further evaluated in APP/PS1 transgenic mice. The TQNP/H102
      obtained better ability in decreasing amyloid plaques, increasing Abeta-degrading
      enzymes, reducing tau protein phosphorylation, protecting synapses and improving
      the spatial learning and memory of transgenic mice than nanoparticles modified
      with a single ligand. And good biocompatibility of TQNP was indicated with
      subacute toxicity assays. In conclusion, TQNP was a valuable nanodevice for the
      precise delivery for biotechnological drugs to treat AD.

PMID- 28432016
TI  - Inkjet printing of antiviral PCL nanoparticles and anticancer cyclodextrin
      inclusion complexes on bioadhesive film for cervical administration.
AB  - Personalized medicine is an important treatment approach for diseases like cancer
      with high intrasubject variability. In this framework, printing is one of the
      most promising methods since it permits dose and geometry adjustment of the final
      product. With this study, a combination product consisting of anticancer
      (paclitaxel) and antiviral (cidofovir) drugs was manufactured by inkjet printing
      onto adhesive film for local treatment of cervical cancers as a result of HPV
      infection. Furthermore, solubility problem of paclitaxel was overcome by
      maintaining this poorly soluble drug in a cyclodextrin inclusion complex and
      release of cidofovir was controlled by encapsulation in polycaprolactone
      nanoparticles. In vitro characterization studies of printed film formulations
      were performed and cell culture studies showed that drug loaded film formulation
      was effective on human cervical adenocarcinoma cells. Our study suggests that
      inkjet printing technology can be utilized in the development of
      antiviral/anticancer combination dosage forms for mucosal application. The drug
      amount in the delivery system can be accurately controlled and modified.
      Moreover, prolonged drug release time can be obtained. Printing of anticancer and
      antiviral drugs on film seem to be a potential approach for HPV-related cervical
      cancer treatment and a good candidate for further studies.

PMID- 28432014
TI  - TREM2-Ligand Interactions in Health and Disease.
AB  - The protein triggering receptor expressed on myeloid cells-2 (TREM2) is an
      immunomodulatory receptor with a central role in myeloid cell activation and
      survival. In recent years, the importance of TREM2 has been highlighted by the
      identification of coding variants that increase risk for Alzheimer's disease and
      other neurodegenerative diseases. Animal studies have further shown the
      importance of TREM2 in neurodegenerative and other inflammatory disease models
      including chronic obstructive pulmonary disease, multiple sclerosis, and stroke.
      A mechanistic understanding of TREM2 function remains elusive, however, due in
      part to the absence of conclusive information regarding the identity of
      endogenous TREM2 ligands. While many TREM2 ligands have been proposed, their
      physiological role and mechanism of engagement remain to be determined. In this
      review, we highlight the suggested roles of TREM2 in these diseases and the
      recent advances in our understanding of TREM2 and discuss putative TREM2-ligand
      interactions and their potential roles in signaling during health and disease. We
      develop a model based on the TREM2 structure to explain how different TREM2
      ligands might interact with the receptor and how disease risk variants may alter
      ligand interactions. Finally, we propose future experimental directions to
      establish the role and importance of these different interactions on TREM2
      function.

PMID- 28432019
TI  - Feasibility of mini-tablets as a flexible drug delivery tool.
AB  - Mini-tablets have potential applications as a flexible drug delivery tool in
      addition to their generally perceived use as multi-particulates. That is, mini
      tablets could provide flexibility in dose finding studies and/or allow for
      combination therapies in the clinic. Moreover, mini-tablets with well controlled
      quality attributes could be a prudent choice for administering solid dosage forms
      as a single unit or composite of multiple mini-tablets in patient populations
      with swallowing difficulties (e.g., pediatric and geriatric populations). This
      work demonstrated drug substance particle size and concentration ranges that
      achieve acceptable mini-tablet quality attributes for use as a single or
      composite dosage unit. Immediate release and orally disintegrating mini-tablet
      formulations with 30MUm to 350MUm (particle size d90) acetaminophen and CompapTM
      L (90% acetaminophen) at concentrations equivalent to 6.7% and 26.7%
      acetaminophen were evaluated. Mini-tablets achieved acceptable weight
      variability, tensile strength, friability, and disintegration time at a
      reasonable solid fraction for each formulation. The content uniformity was
      acceptable for mini-tablets of 6.7% formulations with <=170MUm drug substance,
      mini-tablets of all 26.7% formulations, and composite dosage units containing
      five or more mini-tablets of any formulation. Results supported the manufacturing
      feasibility of quality mini-tablets, and their applicability as a flexible drug
      delivery tool.

PMID- 28432018
TI  - On the role of API in determining porosity, pore structure and bulk modulus of
      the skeletal material in pharmaceutical tablets formed with MCC as sole
      excipient.
AB  - The physical properties and mechanical integrity of pharmaceutical tablets are of
      major importance when loading with active pharmaceutical ingredient(s) (API) in
      order to ensure ease of processing, control of dosage and stability during
      transportation and handling prior to patient consumption. The interaction between
      API and excipient, acting as functional extender and binder, however, is little
      understood in this context. The API indomethacin is combined in this study with
      microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the
      defined API/MCC ratios are made under conditions of controlled porosity and
      tablet thickness, resulting from different compression conditions, and thus
      compaction levels. Mercury intrusion porosimetry is used to establish the
      accessible pore volume, pore size distribution and, adopting the observed region
      of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the
      skeletal material is recorded. Porosity values are compared to previously
      published values derived from terahertz (THz) refractive index data obtained from
      exactly the same tablet sample sets. It is shown that the elastic bulk modulus is
      dependent on API wt% loading under constant tablet preparation conditions
      delivering equal dimensions and porosity. The findings are considered of novel
      value in respect to establishing consistency of tablet production and
      optimisation of physical properties.

PMID- 28432020
TI  - Surface modification of acetaminophen particles by atomic layer deposition.
AB  - Active pharmaceutical ingredients (APIs) are predominantly organic solid powders.
      Due to their bulk properties many APIs require processing to improve
      pharmaceutical formulation and manufacturing in the preparation for various drug
      dosage forms. Improved powder flow and protection of the APIs are often
      anticipated characteristics in pharmaceutical manufacturing. In this work, we
      have modified acetaminophen particles with atomic layer deposition (ALD) by
      conformal nanometer scale coatings in a one-step coating process. According to
      the results, ALD, utilizing common chemistries for Al2O3, TiO2 and ZnO, is shown
      to be a promising coating method for solid pharmaceutical powders. Acetaminophen
      does not undergo degradation during the ALD coating process and maintains its
      stable polymorphic structure. Acetaminophen with nanometer scale ALD coatings
      shows slowed drug release. ALD TiO2 coated acetaminophen particles show
      cytocompatibility whereas those coated with thicker ZnO coatings exhibit the most
      cytotoxicity among the ALD materials under study when assessed in vitro by their
      effect on intestinal Caco-2 cells.

PMID- 28432021
TI  - The ER phagosome connection in the era of membrane contact sites.
AB  - Phagocytosis is an essential mechanism through which innate immune cells ingest
      foreign material that is either destroyed or used to generate and present
      antigens and initiate adaptive immune responses. While a role for the ER during
      phagosome biogenesis has been recognized, whether fusion with ER cisternae or
      vesicular derivatives occurs has been the source of much contention. Membrane
      contact sites (MCS) are tight appositions between ER membranes and various
      organelles that coordinate multiple functions including localized signalling,
      lipid transfer and trafficking. The discovery that MCS form between the ER and
      phagosomes now begs the question of whether MCS play a role in connecting the ER
      to phagosomes under different contexts. In this review, we consider the
      implications of MCS between the ER and phagosomes during cross-presentation and
      infection with intracellular pathogens. We also discuss the similarities between
      these contacts and those between the ER and plasma membrane and acidic organelles
      such as endosomes and lysosomes. This article is part of a Special Issue
      entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit
      Kornmann.

PMID- 28432022
TI  - A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion
      properties of human colon cancer cells.
AB  - Patients with inflammatory bowel disease often suffer from chronic and relapsing
      intestinal inflammation that favor the development of colitis associated cancer.
      An alteration of the epithelial intestinal barrier function observed in IBD is
      supposed to be a consequence of stress. It has been proposed that corticotrophin
      releasing factor receptor (CRF2), one of the two receptors of CRF, the principal
      neuromediator of stress, acts on cholinergic nerves to induce stress-mediated
      epithelial barrier dysfunction. Non-neuronal acetylcholine (Ach) and muscarinic
      receptors (mAchR) also contribute to alterations of epithelial cell functions. In
      this study, we investigated the mechanisms through which stress and Ach modulate
      epithelial cell adhesive properties. We show that Ach-induced activation of mAchR
      in HT-29 cells results in cell dissociation together with changes in cell-matrix
      contacts, which correlates with the acquisition of invasive potential consistent
      with a matrix metalloproteinase (MMP) mode of invasion. These processes result
      from mAchR subsequent stimulation of the cascade of src/Erk and FAK activation.
      Ach-induced secretion of laminin 332 leads to alpha3beta1 integrin activation and
      RhoA-dependent reorganization of the actin cytoskeleton. We show that Ach
      mediated effects on cell adhesion are blocked by astressin 2b, a CRF2 antagonist,
      suggesting that Ach action depends partly on CRF2 signaling. This is reinforced
      by the fact that Ach-mediated activation of mAchR stimulates both the synthesis
      and the release of CRF2 ligands in HT-29 cells (effects blocked by atropine). In
      summary, our data provides evidence for a novel intracellular circuit involving
      mAchR acting on CRF2-signaling that could mediate colonic mucosal barrier
      dysfunction and exacerbate mucosal inflammation.

PMID- 28432023
TI  - Pulmonary embolism related sudden cardiac arrest admitted alive at hospital:
      Management and outcomes.
AB  - AIM: Pulmonary Embolism (PE) is a relatively common cardiovascular condition,
      occasionally and tragically manifesting as Sudden Cardiac Arrest (SCA). The
      natural history of SCA complicating PE has been poorly evaluated.In this study,
      we described the management and outcome of PE-related SCA. METHODS: In this
      prospective population--based study, we included all patients admitted at
      hospital alive after out- of- hospital SCA, in Paris and suburbs, France (6.6
      million inhabits), from May 2011 to September 2015. RESULTS: Of 2926 patients
      hospitalized after SCA, 82 cases were diagnosed as PE-related SCA (2.8%,
      95%CI=2.2-3.4). Systemic thrombolysis was performed in 47 patients (57%), without
      significant increased risk of major bleeding among patients treated with
      thrombolysis. 12 patients (15%) were treated with ECLS, 29 patients (36%) had
      targeted temperature management, and 20 patients (24%) underwent coronary
      angiography. 94% of PE-related SCA had initial non-shockable rhythm, and were
      associated with better survival compared with other non-shockable SCA (crude
      OR=3.0, 95%CI=1.7-5.4, P <0.001; adjusted OR=4.1, 95%CI 2.0-8.3, P<0.001). Among
      PE-related SCA, thrombolysis was independently associated with survival (OR=12.5,
      95%CI=1.8-89.1, P=0.01). Multiple sensitivity analysis was performed, with
      consistent results. CONCLUSIONS: PE is responsible of approximately 3% of
      hospitalizations for SCA. Thrombolysis was associated with an increased survival
      in this population, reinforcing current guidelines advocating for such treatment
      in PE-related SCA.

PMID- 28432024
TI  - Re: Chen et al.'s letter regarding the article "Effect of prehospital advanced
      airway management for pediatric out-of-hospital cardiac arrest.": Video
      laryngoscope use and time to intubation for pediatric out-of-hospital cardiac
      arrest.

PMID- 28432025
TI  - Improving telephone CPR - The devil is in the details.

PMID- 28432026
TI  - Reply to: Accurate neuroprognostication in cardiac arrest survivors: Details
      matter!

PMID- 28432027
TI  - Introduction to neuroscience letters special issue: "Plasticity and regeneration
      after spinal cord injury".

PMID- 28432028
TI  - Evaluation of Se-phenyl-thiazolidine-4-carboselenoate protective activity against
      oxidative and behavioral stress in the maniac model induced by ouabain in male
      rats.
AB  - This study investigates Se-phenyl-thiazolidine-4-carboselenoate (Se-PTC)
      protective activity against oxidative and behavioral stress in the model of mania
      induced by ouabain (OUA) in male rats. The compound used was Se-PTC (50mg/kg) and
      the positive control LiCl (45mg/kg) was administered for intragastric route
      (i.g.) 30min prior to administration of OUA (10-5M). OUA was dissolved in
      artificial cerebrospinal fluid (aCSF) and administered at the 5MUl through an
      intracerebroventricular (i.c.v) cannula. The pretreatment with Se-PTC was
      effective in preventing the increase in locomotor activity induced by OUA,
      however the positive control LiCl is capable to block crossing augmentation
      induced by OUA. Na+/K+-ATPase activity was significantly reduced in OUA group and
      the Se-PTC to normalize Na+/K+-ATPase activity. Pretreatment with Se-PTC protect
      against the increase in catalase activity and thiobarbituric acid reactive
      species (TBARS) content in the brain caused by OUA. Therefore, Se-PTC is
      effective against OUA-induced hyperactivity and alterations in brain oxidative
      status of rats.

PMID- 28432029
TI  - Suppression of reward-induced dopamine release in the nucleus accumbens in animal
      models of depression: Differential responses to drug treatment.
AB  - Anhedonia, the loss of interest or pleasure in previously enjoyable activities,
      is a core symptom of major depressive disorder, suggesting that the brain reward
      system may be dysfunctional in this condition. Neurochemical changes in the
      mesolimbic dopamine (DA) system are not fully understood in animal models of
      depression. We investigated reward (30% sucrose intake)-induced DA release in the
      nucleus accumbens (NAc) and the effect of chronic treatment with the
      antidepressant escitalopram (5mg/kg, intraperitoneally twice daily for 3 weeks)
      in two animal models of depression. Exposure to chronic mild stress (CMS) during
      adulthood completely suppressed reward-induced intra-NAc DA release; however,
      this effect was reversed by chronic treatment with escitalopram. Our findings
      suggest that reward-induced intra-NAc DA release may be an indicator of
      depression severity and therapeutic efficacy. Exposure to neonatal maternal
      separation (MS) and CMS in adulthood completely suppressed reward-induced intra
      NAc DA release. Chronic treatment with escitalopram did not restore reward
      induced DA release in these animals, suggesting that this paradigm may serve as
      an animal model for treatment-resistant depression. Further study of the
      mesolimbic dopaminergic system in these animal models of depression may clarify
      the neural mechanisms underlying depression and treatment resistance.

PMID- 28432030
TI  - Effects of mixed proximal and distal topogenic signals on the topological
      sensitivity of a membrane protein to the lipid environment.
AB  - The final topology of membrane proteins is thought to be dictated primarily by
      the encoding sequence. However, according to the Charge Balance Rule the
      topogenic signals within nascent membrane proteins are interpreted in agreement
      with the Positive Inside Rule as influenced by the protein phospholipid
      environment. The role of long-range protein-lipid interactions in establishing a
      final uniform or dual topology is unknown. In order to address this role, we
      determined the positional dependence of the potency of charged residues as
      topological signals within Escherichia coli sucrose permease (CscB) in cells in
      which the zwitterionic phospholipid phosphatidylethanolamine (PE), acting as
      topological determinant, was either eliminated or tightly titrated. Although the
      position of a single or paired oppositely charged amino acid residues within an
      extramembrane domain (EMD), either proximal, central or distal to a transmembrane
      domain (TMD) end, does not appear to be important, the oppositely charged
      residues exert their topogenic effects separately only in the absence of PE.
      Thus, the Charge Balance Rule can be executed in a retrograde manner from any
      cytoplasmic EMD or any residue within an EMD most likely outside of the
      translocon. Moreover, CscB is inserted into the membrane in two opposite
      orientations at different ratios with the native orientation proportional to the
      mol % of PE. The results demonstrate how the cooperative contribution of lipid
      protein interactions affects the potency of charged residues as topological
      signals, providing a molecular mechanism for the realization of single, equal or
      different amounts of oppositely oriented protein within the same membrane.

PMID- 28432031
TI  - Membrane Lipid Replacement for chronic illnesses, aging and cancer using oral
      glycerolphospholipid formulations with fructooligosaccharides to restore
      phospholipid function in cellular membranes, organelles, cells and tissues.
AB  - Membrane Lipid Replacement is the use of functional, oral supplements containing
      mixtures of cell membrane glycerolphospholipids, plus fructooligosaccharides (for
      protection against oxidative, bile acid and enzymatic damage) and antioxidants,
      in order to safely replace damaged, oxidized, membrane phospholipids and restore
      membrane, organelle, cellular and organ function. Defects in cellular and
      intracellular membranes are characteristic of all chronic medical conditions,
      including cancer, and normal processes, such as aging. Once the replacement
      glycerolphospholipids have been ingested, dispersed, complexed and transported,
      while being protected by fructooligosaccharides and several natural mechanisms,
      they can be inserted into cell membranes, lipoproteins, lipid globules, lipid
      droplets, liposomes and other carriers. They are conveyed by the lymphatics and
      blood circulation to cellular sites where they are endocytosed or incorporated
      into or transported by cell membranes. Inside cells the glycerolphospholipids can
      be transferred to various intracellular membranes by lipid globules, liposomes,
      membrane-membrane contact or by lipid carrier transfer. Eventually they arrive at
      their membrane destinations due to 'bulk flow' principles, and there they can
      stimulate the natural removal and replacement of damaged membrane lipids while
      undergoing further enzymatic alterations. Clinical trials have shown the benefits
      of Membrane Lipid Replacement in restoring mitochondrial function and reducing
      fatigue in aged subjects and chronically ill patients. Recently Membrane Lipid
      Replacement has been used to reduce pain and other symptoms as well as removing
      hydrophobic chemical contaminants, suggesting that there are additional new uses
      for this safe, natural medicine supplement. This article is part of a Special
      Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by
      Pablo V. Escriba.

PMID- 28432032
TI  - Neuronal excitation and permeabilization by 200-ns pulsed electric field: An
      optical membrane potential study with FluoVolt dye.
AB  - Electric field pulses of nano- and picosecond duration are a novel modality for
      neurostimulation, activation of Ca2+ signaling, and tissue ablation. However it
      is not known how such brief pulses activate voltage-gated ion channels. We
      studied excitation and electroporation of hippocampal neurons by 200-ns pulsed
      electric field (nsPEF), by means of time-lapse imaging of the optical membrane
      potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more
      depolarized level, which was reached within <1ms. The OMP recovery started
      rapidly (tau=8-12ms) but gradually slowed down (to tau>10s), so cells remained
      above the resting OMP level for at least 20-30s. Activation of voltage-gated
      sodium channels (VGSC) enhanced the depolarizing effect of electroporation,
      resulting in an additional tetrodotoxin-sensitive OMP peak in 4-5ms after nsPEF.
      Omitting Ca2+ in the extracellular solution did not reduce the depolarization,
      suggesting no contribution of voltage-gated calcium channels (VGCC). In 40% of
      neurons, nsPEF triggered a single action potential (AP), with the median
      threshold of 3kV/cm (range: 1.9-4kV/cm); no APs could be evoked by stimuli below
      the electroporation threshold (1.5-1.9kV/cm). VGSC opening could already be
      detected in 0.5ms after nsPEF, which is too fast to be mediated by the
      depolarizing effect of electroporation. The overlap of electroporation and AP
      thresholds does not necessarily reflect the causal relation, but suggests a low
      potency of nsPEF, as compared to conventional electrostimulation, for VGSC
      activation and AP induction.

PMID- 28432033
TI  - Lipids as central modulators of sensory TRP channels.
AB  - The transient receptor potential (TRP) ion channel family is involved in a
      diversity of physiological processes including sensory and homeostatic functions,
      as well as muscle contraction and vasomotor control. Their dysfunction
      contributes to the etiology of several diseases, being validated as therapeutic
      targets. These ion channels may be activated by physical or chemical stimuli and
      their function is highly influenced by signaling molecules activated by
      extracellular signals. Notably, as integral membrane proteins, lipid molecules
      also modulate their membrane location and function either by direct interaction
      with the channel structure or by modulating the physico-chemical properties of
      the cellular membrane. This lipid-based modulatory effect is being considered an
      alternative and promising approach to regulate TRP channel dysfunction in
      diseases. Here, we review the current progress in this exciting field
      highlighting a complex channel regulation by a large diversity of lipid molecules
      and suggesting some diseases that may benefit from a membrane lipid therapy. This
      article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs
      Targeting Biomembranes edited by Pablo V. Escriba.

PMID- 28432034
TI  - Frequency spectrum of induced transmembrane potential and permeabilization
      efficacy of bipolar electric pulses.
AB  - In this paper a simple prediction method for the bipolar pulse cancellation
      effect is proposed, based on the frequency analysis of the TMP spectra of a
      single cell and the computed relative global spectral content up to a defined
      frequency threshold. We present a spectral analysis of pulses applied in
      experiments, and we extract the induced TMP from a microdosimetric model of the
      cell. The induced TMP computation is carried out on a hemispherical multi-layered
      cell model in the time domain. The analysis is presented for a variety of
      unipolar and bipolar input signals in the nanosecond and the microsecond time
      scales. Our evaluations are in good agreement with experimental results for
      bipolar pulse cancellation of electropermeabilization-induced Ca2+ influx using
      300ns, 750kV/m pulses and with other results reported in recent literature.

PMID- 28432035
TI  - Expression of pattern recognition receptors and activation of the non-canonical
      inflammasome pathway in brain pericytes.
AB  - Cerebral pericytes are mural cells embedded in the basement membrane of
      capillaries. Increasing evidence suggests that they play important role in
      controlling neurovascular functions, i.e. cerebral blood flow, angiogenesis and
      permeability of the blood-brain barrier. These cells can also influence
      neuroinflammation which is highly regulated by the innate immune system.
      Therefore, we systematically tested the pattern recognition receptor expression
      of brain pericytes. We detected expression of NOD1, NOD2, NLRC5, NLRP1-3, NLRP5,
      NLRP9, NLRP10 and NLRX mRNA in non-treated cells. Among the ten known human TLRs,
      TLR2, TLR4, TLR5, TLR6 and TLR10 were found to be expressed. Inflammatory
      mediators induced the expression of NLRA, NLRC4 and TLR9 and increased the levels
      of NOD2, TLR2, inflammasome-forming caspases and inflammasome-cleaved
      interleukins. Oxidative stress, on the other hand, upregulated expression of
      TLR10 and NLRP9. Activation of selected pattern recognition receptors can lead to
      inflammasome assembly and caspase-dependent secretion of IL-1beta. TNF-alpha and
      IFN-gamma increased the levels of pro-IL-1beta and pro-caspase-1 proteins;
      however, no canonical activation of NLRP1, NLRP2, NLRP3 or NLRC4 inflammasomes
      could be observed in human brain vascular pericytes. On the other hand, we could
      demonstrate secretion of active IL-1beta in response to non-canonical
      inflammasome activation, i.e. intracellular LPS or infection with E. coli
      bacteria. Our in vitro results indicate that pericytes might have an important
      regulatory role in neuroinflammation.

PMID- 28432036
TI  - Increased inflammation from childhood to adolescence predicts sleep apnea in
      boys: A preliminary study.
AB  - While chronic systemic inflammation in obstructive sleep apnea (OSA) has been
      traditionally considered a consequence of intermittent hypoxia, several treatment
      studies targeting inflammation suggest that this process may precede the
      development of the disorder. A recent cross-sectional study in the Penn State
      Child Cohort (PSCC) revealed that inflammation largely mediates the association
      between visceral adiposity and OSA in adolescence. The purpose of this study was
      to examine for the first time whether, longitudinally, inflammation precedes OSA
      during this developmental period. A subsample of the PSCC with longitudinal sleep
      and inflammation data (n=51) was included in this study. Participants underwent 9
      h polysomnography (22:00-7:00), physical exam, and fasting morning blood draw at
      both time points. Plasma C-reactive protein (CRP) was measured via ELISA. At
      follow-up, visceral, subcutaneous, and total fat area were assessed via dual X
      ray absorptiometry. Sex differences in body composition emerged in adolescence,
      with boys having more visceral adiposity than girls. Longitudinal increases in
      waist circumference from childhood to adolescence were associated with increases
      in CRP (DeltaCRP) and follow-up CRP in boys, but not girls. Furthermore, in boys,
      DeltaCRP was associated with higher follow-up apnea/hypopnea index (AHI). When
      DeltaCRP was entered into a model predicting follow-up AHI, Deltawaist
      circumference was no longer significant, indicating that inflammation largely
      explains the association between increasing central obesity and OSA severity.
      These preliminary findings, in a longitudinal, non-clinical sample of children
      developing OSA, suggest that inflammation derived from visceral adipose tissue
      precedes the development of the disorder, suggesting a potential causal
      mechanism.

PMID- 28432037
TI  - Investigating in vitro and in vivo alphavbeta6 integrin receptor-targeting
      liposomal alendronate for combinatory gammadelta T cell immunotherapy.
AB  - The alphavbeta6 integrin receptor has been shown to be overexpressed on many
      types of cancer cells, resulting in a more pro-invasive and aggressive phenotype,
      this makes it an attractive target for selective drug delivery. In tumours that
      over-express the alphavbeta6 receptor, cellular uptake of liposomes can be
      enhanced using ligand-targeted liposomes. It has previously been shown in both in
      vitro and in vivo studies that liposomal alendronate (L-ALD) can sensitise cancer
      cells to destruction by Vgamma9Vdelta2 T cells. It is hypothesised that by using
      the alphavbeta6-specific peptide A20FMDV2 as a targeting moiety for L-ALD, the
      therapeutic efficacy of this therapy can be increased in alphavbeta6 positive
      tumours. Targeted liposomes (t-L) were formulated and the targeting efficacy of
      targeted liposomes (t-L) was assessed by cell uptake and cytotoxicity studies in
      the alphavbeta6 positive cells line A375Pbeta6. Bio-distribution of both L and t
      L were carried out in alphavbeta6 positive (A375Pbeta6 and PANC0403) and
      alphavbeta6 negative (A375Ppuro and PANC-1) subcutaneous tumour mouse models.
      Immuno-compromised mice bearing A375Pbeta6 experimental metastatic lung tumours
      were treated with L-ALD or t-L-ALD as monotherapies or in combination with ex
      vivo-expanded Vgamma9Vdelta2 T cells. In vitro, alphavbeta6-dependant uptake of t
      L was observed, with t-L-ALD being more effective than L-ALD at sensitising
      A375Pbeta6 to gammadelta T cells. Interestingly, t-L-ALD led to slightly higher
      but not significant reduction in tumour growth compared to L-ALD, when used as
      monotherapy in vivo. Moreover, both L-ALD and t-L-ALD led to significant
      reductions in tumour growth when used in combination with gammadelta T cells in
      vivo but t-L-ALD offered no added advantage compared to L-ALD.

PMID- 28432039
TI  - Simulation Training: Evaluating the Instructor's Contribution to a Wizard of Oz
      Simulator in Obstetrics and Gynecology Ultrasound Training.
AB  - BACKGROUND: Workplaces today demand graduates who are prepared with field
      specific knowledge, advanced social skills, problem-solving skills, and
      integration capabilities. Meeting these goals with didactic learning (DL) is
      becoming increasingly difficult. Enhanced training methods that would better
      prepare tomorrow's graduates must be more engaging and game-like, such as
      feedback based e-learning or simulation-based training, while saving time.
      Empirical evidence regarding the effectiveness of advanced learning methods is
      lacking. Objective quantitative research comparing advanced training methods with
      DL is sparse. OBJECTIVES: This quantitative study assessed the effectiveness of a
      computerized interactive simulator coupled with an instructor who monitored
      students' progress and provided Web-based immediate feedback. METHODS: A low
      cost, globally accessible, telemedicine simulator, developed at the Technion
      Israel Institute of Technology, Haifa, Israel-was used. A previous study in the
      field of interventional cardiology, evaluating the efficacy of the simulator to
      enhanced learning via knowledge exams, presented promising results of average
      scores varying from 94% after training and 54% before training (n=20) with
      P<.001. Two independent experiments involving obstetrics and gynecology (Ob-Gyn)
      physicians and senior ultrasound sonographers, with 32 subjects, were conducted
      using a new interactive concept of the WOZ (Wizard of OZ) simulator platform. The
      contribution of an instructor to learning outcomes was evaluated by comparing
      students' knowledge before and after each interactive instructor-led session as
      well as after fully automated e-learning in the field of Ob-Gyn. Results from
      objective knowledge tests were analyzed using hypothesis testing and model
      fitting. RESULTS: A significant advantage (P=.01) was found in favor of the WOZ
      training approach. Content type and training audience were not significant.
      CONCLUSIONS: This study evaluated the contribution of an integrated teaching
      environment using a computerized interactive simulator, with an instructor
      providing immediate Web-based immediate feedback to trainees. Involvement of an
      instructor in the simulation-based training process provided better learning
      outcomes that varied training content and trainee populations did not affect the
      overall learning gains.

PMID- 28432038
TI  - Seeking Web-Based Information About Attention Deficit Hyperactivity Disorder:
      Where, What, and When.
AB  - BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common
      neurodevelopmental disorder, prevalent among 2-10% of the population. OBJECTIVE:
      The objective of this study was to describe where, what, and when people search
      online for topics related to ADHD. METHODS: Data were collected from Microsoft's
      Bing search engine and from the community question and answer site, Yahoo
      Answers. The questions were analyzed based on keywords and using further
      statistical methods. RESULTS: Our results revealed that the Internet indeed
      constitutes a source of information for people searching the topic of ADHD, and
      that they search for information mostly about ADHD symptoms. Furthermore,
      individuals personally affected by the disorder made 2.0 more questions about
      ADHD compared with others. Questions begin when children reach 2 years of age,
      with an average age of 5.1 years. Most of the websites searched were not
      specifically related to ADHD and the timing of searches as well as the query
      content were different among those prediagnosis compared with postdiagnosis.
      CONCLUSIONS: The study results shed light on the features of ADHD-related
      searches. Thus, they may help improve the Internet as a source of reliable
      information, and promote improved awareness and knowledge about ADHD as well as
      quality of life for populations dealing with the complex phenomena of ADHD.

PMID- 28432041
TI  - Suicide risk article points in the wrong direction.

PMID- 28432040
TI  - Usability, Acceptability, and Adherence to an Electronic Self-Monitoring System
      in Patients With Major Depression Discharged From Inpatient Wards.
AB  - BACKGROUND: Patients suffering from depression have a high risk of relapse and
      readmission in the weeks following discharge from inpatient wards. Electronic
      self-monitoring systems that offer patient-communication features are now
      available to offer daily support to patients, but the usability, acceptability,
      and adherence to these systems has only been sparsely investigated. OBJECTIVE: We
      aim to test the usability, acceptability, adherence, and clinical outcome of a
      newly developed computer-based electronic self-assessment system (the Daybuilder
      system) in patients suffering from depression, in the period from discharge until
      commencing outpatient treatment in the Intensive Outpatient Unit for Affective
      Disorders. METHODS: Patients suffering from unipolar major depression that were
      referred from inpatient wards to an intensive outpatient unit were included in
      this study before their discharge, and were followed for four weeks. User
      satisfaction was assessed using semiqualitative questionnaires and the System
      Usability Scale (SUS). Patients were interviewed at baseline and at endpoint with
      the Hamilton depression rating scale (HAM-D17), the Major Depression Inventory
      (MDI), and the 5-item World Health Organization Well-Being Index (WHO-5). In this
      four-week period patients used the Daybuilder system to self-monitor mood, sleep,
      activity, and medication adherence on a daily basis. The system displayed a
      graphical representation of the data that was simultaneously displayed to
      patients and clinicians. Patients were phoned weekly to discuss their data
      entries. The primary outcomes were usability, acceptability, and adherence to the
      system. The secondary outcomes were changes in: the electronically self-assessed
      mood, sleep, and activity scores; and scores from the HAM-D17, MDI, and WHO-5
      scales. RESULTS: In total, 76% of enrolled patients (34/45) completed the four
      week study. Five patients were readmitted due to relapse. The 34 patients that
      completed the study entered data for mood on 93.8% of the days (872/930), sleep
      on 89.8% of the days (835/930), activity on 85.6% of the days (796/930), and
      medication on 88.0 % of the days (818/930). SUS scores were 86.2 (standard
      deviation [SD] 9.7) and 79% of the patients (27/34) found that the system lived
      up to their expectations. A significant improvement in depression severity was
      found on the HAM-D17 from 18.0 (SD 6.5) to 13.3 (SD 7.3; P<.01), on the MDI from
      27.1 (SD 13.1) to 22.1 (SD 12.7; P=.006), and in quality of life on the WHO-5
      from 31.3 (SD 22.9) to 43.4 (SD 22.1; P<.001) scales, but not on self-assessed
      mood (P=.08). Mood and sleep parameters were highly variable from day-to-day.
      Sleep-offset was significantly delayed from baseline, averaging 48 minutes
      (standard error 12 minutes; P<.001). Furthermore, when estimating delay of sleep
      onset (with sleep quality included in the model) during the study period, this
      showed a significant negative effect on mood (P=.03). CONCLUSIONS: The Daybuilder
      systems performed well technically, and patients were satisfied with the system
      and had high adherence to self-assessments. The dropout rate and the gradual
      delay in sleep emphasize the need for continued clinical support for these
      patients, especially when considering sleep guidance.

PMID- 28432042
TI  - Syndrome of inappropriate antidiuretic hormone accompanied by bilateral
      hypothalamic and anterior thalamic lesions with serum antiaquaporin 4 antibody.
AB  - We described a rare case of the syndrome of inappropriate antidiuretic hormone
      secretion (SIADH) and severe unconsciousness accompanied by bilateral
      hypothalamic and anterior thalamic lesions with positive serum antiaquaporin 4
      (AQP4) antibody. A 29-year-old man was admitted to our hospital due to the
      subacute progression of an unconscious state. He was observed to be hyponatraemic
      secondary to SIADH. Brain MRI showed bilateral hypothalamic and anterior thalamic
      lesions. Anti-AQP4 antibody was detected in his serum. After the administration
      of intravenous methylprednisolone pulse therapy, his symptoms improved with
      complete recovery from SIADH and regression of the hypothalamic and anterior
      thalamic lesions. The patient was transferred to another hospital for
      rehabilitation with 20 mg/day of oral prednisolone 127 days after admission. This
      case highlights the importance of testing for anti-AQP4 antibody in patients with
      unexplainable SIADH, subacute progressive unconsciousness and bilateral
      hypothalamic and anterior thalamic lesions.

PMID- 28432043
TI  - Transoesophageal three-dimensional echocardiographic diagnosis of Barlow's
      disease.

PMID- 28432044
TI  - Charles David Lacey.

PMID- 28432045
TI  - India passes law prohibiting discrimination against people with HIV/AIDS.

PMID- 28432046
TI  - Brodie abscess of the femoral capital epiphysis in a 2-year-old child caused by
      Kingella kingae.
AB  - We report the case of a Brodie abscess of the femoral capital epiphysis from
      which Kingella kingae was isolated. This is to the best of our knowledge the
      first report of a Brodie abscess of the femoral capital epiphysis from which K.
      kingae was isolated.

PMID- 28432047
TI  - Delayed LGI1 seropositivity in voltage-gated potassium channel (VGKC)-complex
      antibody limbic encephalitis.
AB  - We utilise a clinical case to highlight why exclusion of voltage-gated potassium
      channel (VGKC)-complex autoantibody testing in serological evaluation of patients
      may delay or miss the diagnosis. A 68-year-old man presented with increasing
      involuntary movements consistent with faciobrachial dystonic seizures (FBDS).
      Initial evaluation demonstrated VGKC antibody seropositivity with leucine-rich
      glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2)
      seronegativity. Aggressive immunotherapy with methylprednisolone and
      plasmapheresis was started early in the course of his presentation. Following
      treatment with immunotherapy, the patient demonstrated clinical improvement.
      Repeat serum evaluation 4 months posthospitalisation remained seropositive for
      VGKC-complex antibodies, with development of LGI1 autoantibody seropositivity.
      VGKC-complex and LGI1 antibodies remained positive 12 months posthospitalisation.
      Our findings suggest that clinical symptoms can predate the detection of the
      antibody. We conclude that when suspicion for autoimmune encephalitis is high in
      the setting of VGKC autoantibody positivity, regardless of LGI1 or CASPR2
      seropositivity, early immunotherapy and repeat testing should be considered.

PMID- 28432048
TI  - Solithromycin: A novel ketolide antibiotic.
AB  - PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial
      activity, clinical safety, and current regulatory status of solithromycin are
      reviewed. SUMMARY: Solithromycin is a novel ketolide antibiotic developed for the
      treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic,
      pharmacokinetic, and pharmacodynamic properties provide activity against a broad
      range of intracellular organisms, including retained activity against pathogens
      displaying various mechanisms of macrolide resistance. Phase III clinical trials
      of solithromycin demonstrated noninferiority of both oral and i.v.-to-oral
      regimens of 5-7 days' duration compared with moxifloxacin for patients with
      moderately severe CABP. Nearly one third of patients receiving i.v. solithromycin
      experienced infusion-site reactions. Although no liver-related adverse events
      were reported in patients receiving oral solithromycin, more patients receiving
      i.v.-to-oral solithromycin experienced asymptomatic, transient transaminitis,
      with alanine transaminase levels of >3 to >5 times the upper limit, compared with
      those treated with moxifloxacin. These results led the Food and Drug
      Administration to conclude that the solithromycin new drug application was not
      approvable as filed, adding that the risk of hepatotoxicity had not yet been
      adequately characterized. The agency further recommended a comparative study of
      patients with CABP to include approximately 9,000 patients exposed to
      solithromycin in order to exclude drug-induced liver injury events occurring at a
      rate of 1 in 3,000 with 95% probability. CONCLUSION: Solithromycin is a novel
      ketolide antibiotic with activity against a broad spectrum of intracellular
      organisms, including those displaying macrolide resistance. While demonstrating
      noninferiority to a current first-line agent in the treatment of CABP, concerns
      for drug-induced liver injury and infusion-site reactions have placed its
      regulatory future in doubt.

PMID- 28432049
TI  - Randomized controlled trial of different aspirin regimens for reduction of niacin
      induced flushing.
AB  - PURPOSE: Results of a study to test the hypothesis that taking niacin
      simultaneously with different forms of aspirin would reduce the occurrence of
      niacin-induced flushing are reported. METHODS: Traditionally, taking enteral
      absorbed aspirin 30 minutes before a niacin dose has been shown to reduce
      flushing by 30-50% relative to nonuse of aspirin. The objective of the study was
      to evaluate the efficacy of enteral absorbed and orally dissolved aspirin, taken
      at the same time as niacin, in reducing the frequency of moderate-to-severe
      flushing. In a prospective, double-blind, placebo-controlled crossover trial,
      healthy adult male and female volunteers were asked to take aspirin or a placebo
      (both agents were taken in both orally dissolved and swallowed formulations)
      immediately before niacin administration. Subjects then self-evaluated flushing
      symptoms on a validated scale. RESULTS: Simultaneous administration of swallowed
      aspirin and niacin reduced moderate-to-severe flushing events by a mean of 36.1%,
      from 2.35 to 1.5 events per subject (p = 0.003), relative to event rates with use
      of niacin alone. In a subset of subjects who had experienced moderate-to-severe
      flushing symptoms despite taking swallowed aspirin, flushing in response to
      subsequent niacin use was decreased by 20.5% (p = 0.05) with coadministration of
      orally dissolved aspirin and by 18.0% with a regimen containing both orally
      dissolved and swallowed aspirin (p = 0.03). CONCLUSION: Novel regimens of niacin
      and aspirin, including orally dissolved aspirin, were effective in reducing
      niacin-induced flushing in a small sample of healthy adult volunteers.

PMID- 28432051
TI  - Impact of study outcome on submission and acceptance metrics for peer reviewed
      medical journals: six year retrospective review of all completed GlaxoSmithKline
      human drug research studies.
AB  - Objectives To determine whether the outcome of drug studies influenced submission
      and/or acceptance rates for publication in peer reviewed medical journals.Design
      A six year retrospective review of publication status by study outcome for all
      human drug research studies conducted by a single industry sponsor
      (GlaxoSmithKline) that completed from 1 January 2009 to 30 June 2014 and were
      therefore due for manuscript submission (per the sponsor's policy) to peer
      reviewed journals within 18 months of study completion-that is, 31 December 2015.
      In addition, manuscripts from studies completing after 30 June 2014 were included
      irrespective of outcome if they were submitted before 31 December 2015.Setting
      Studies conducted by a single industry sponsor (GlaxoSmithKline)Studies reviewed
      1064 human drug research studies.Main outcome measures All studies were assigned
      a publication status at 26 February 2016 including (as applicable): study
      completion date, date of first primary manuscript submission, number of
      submissions, journal decision(s), and publication date. All studies were also
      classified with assessors blinded to publication status as "positive" (perceived
      favorable outcome for the drug under study), "negative" (perceived unfavorable
      outcome for the drug under study), mixed, or non-comparative based on the
      presence and outcome of the primary outcome measure(s) for each study. "Negative"
      studies included safety studies in which the primary outcome was achieved but was
      adverse for the drug under study. For the total cohort and each of the four study
      outcomes, measures included descriptive statistics for study phase, time from
      study completion to submission and publication, and number and outcome
      (accepted/rejected) of publication submissions.Results Of the 1064 studies (phase
      I-IV, interventional and non-interventional) included, 321 had study outcomes
      classified as positive, 155 as negative, 52 as mixed, and 536 as non-comparative.
      At the time of publication cut-off date (26 February 2016), 904 (85%) studies had
      been submitted for publication as full manuscripts and 751 (71%) had been
      successfully published or accepted, with 100 (9%) still under journal review. An
      additional 77 (7%) studies were conference abstracts and were not included in
      submission or publication rates. Submission rates by study outcome were 79% for
      the 321 studies with positive outcomes, 92% for the 155 with negative outcomes,
      94% for the 52 with mixed outcomes, and 85% for the 536 non-comparative studies;
      while rates of publication at the cut-off date were 66%, 77%, 77%, and 71%,
      respectively. Median time from study completion to submission was 537 days
      (interquartile range 396-638 days) and 823 days (650-1063 days) from completion
      to publication, with similar times observed across study outcomes. First time
      acceptance rates were 56% for studies with positive outcomes and 48% for studies
      with negative outcomes. Over 10% of studies across all categories required three
      or more submissions to achieve successful publication. At the time of analysis,
      83 studies had not been submitted for publication, including 49 bioequivalence
      studies with positive outcomes and 33 non-comparative studies. Most studies (98%,
      1041/1064) had results posted to one or more public registers, including all
      studies subject to FDAAA (Food and Drug Administration Amendments Act)
      requirements for posting to www.clinicaltrials.govConclusions Over the period
      studied, there was no evidence of submission or publication bias: 92% of studies
      with negative outcomes were submitted for publication by the cut-off date versus
      79% of those with positive outcomes. Publication rates were slightly higher for
      studies with a negative (that is, unfavorable) outcome compared with a positive
      outcome, despite a slightly lower rate of acceptance at first submission. Many
      studies required multiple submission attempts before they were accepted for
      publication. Analyses focusing solely on publication rates do not take into
      account unsuccessful efforts to publish. Sponsors and journal editors should
      share similar information to contribute to better understanding of issues and
      barriers to full transparency.

PMID- 28432050
TI  - Prevalence of remission and its effect on damage and quality of life in Chinese
      patients with systemic lupus erythematosus.
AB  - OBJECTIVES: To study the prevalence of remission and its effect on damage and
      quality of life (QOL) in Chinese patients with systemic lupus erythematosus
      (SLE). METHODS: Patients who fulfilled >=4 American College of Rheumatology
      criteria for SLE were identified. Their remission status at last clinic visits
      was determined by the European consensus criteria (complete/clinical remission +/
      immunosuppressive drugs). The increase in SLE damage index (SDI) in the
      preceding 5 years was compared between patients who were and were not in
      remission for >=5 years. QOL of patients as assessed by the validated Chinese
      version of the Medical Outcomes Study Short-Form-36 (SF36) and the LupusPRO was
      also compared between the remission and non-remission groups by statistical
      analysis. RESULTS: 769 SLE patients were studied (92% women; age: 46.4+/-14.6
      years; SLE duration: 12.6+/-8.1 years). At last visit, clinical remission was
      present in 259 (33.7%) patients and complete remission was present in 280 (36.4%)
      patients. Clinical and complete remissions for >=5 years were achieved in 64
      (8.3%) and 129 (16.8%) of the patients, respectively. Patients remitted for >=5
      years were older, and had significantly lower prevalence of renal involvement,
      leucopenia or thrombocytopaenia. Fifty-three (6.9%) patients in remission >=5
      years were taken off all medications, including hydroxychloroquine (HCQ) (drug
      free). Patients who remitted for >=5 years but off-therapy (except HCQ) had
      significantly less SDI increment than those who did not remit (0.17+/-0.53 vs
      0.67+/-1.10; p<0.001). Among 453 patients who had QOL assessment, remission for
      >=5 years was associated with significantly higher SF36 and the total health
      related scores of the LupusPRO. CONCLUSIONS: Durable remission can be achieved in
      a quarter of patients with SLE. Patients with remission for >=5 years have
      significantly less damage accrual and better QOL. Prolonged remission is an
      appropriate criterion for outcome assessment in SLE.

PMID- 28432053
TI  - Joanna Louise Richardson.

PMID- 28432052
TI  - Genomic Instability in Cancer: Teetering on the Limit of Tolerance.
AB  - Cancer genomic instability contributes to the phenomenon of intratumoral genetic
      heterogeneity, provides the genetic diversity required for natural selection, and
      enables the extensive phenotypic diversity that is frequently observed among
      patients. Genomic instability has previously been associated with poor prognosis.
      However, we have evidence that for solid tumors of epithelial origin, extreme
      levels of genomic instability, where more than 75% of the genome is subject to
      somatic copy number alterations, are associated with a potentially better
      prognosis compared with intermediate levels under this threshold. This has been
      observed in clonal subpopulations of larger size, especially when genomic
      instability is shared among a limited number of clones. We hypothesize that
      cancers with extreme levels of genomic instability may be teetering on the brink
      of a threshold where so much of their genome is adversely altered that cells
      rarely replicate successfully. Another possibility is that tumors with high
      levels of genomic instability are more immunogenic than other cancers with a less
      extensive burden of genetic aberrations. Regardless of the exact mechanism, but
      hinging on our ability to quantify how a tumor's burden of genetic aberrations is
      distributed among coexisting clones, genomic instability has important
      therapeutic implications. Herein, we explore the possibility that a high genomic
      instability could be the basis for a tumor's sensitivity to DNA-damaging
      therapies. We primarily focus on studies of epithelial-derived solid tumors.
      Cancer Res; 77(9); 2179-85. (c)2017 AACR.

PMID- 28432054
TI  - Arkansas execution proceeds as pharma companies lose battle to stop use of their
      drugs.

PMID- 28432056
TI  - WHO surgical safety checklist cuts post-surgical deaths by 22%, US study finds.

PMID- 28432057
TI  - Imaging and modeling of acute pressure-induced changes of collagen and elastin
      microarchitectures in pig and human resistance arteries.
AB  - The impact of disease-related changes in the extracellular matrix (ECM) on the
      mechanical properties of human resistance arteries largely remains to be
      established. Resistance arteries from both pig and human parietal pericardium
      (PRA) display a different ECM microarchitecture compared with frequently used
      rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA
      mirror pressure-induced changes in the ECM microarchitecture. This was tested
      using isolated pig PRA as a model system, integrating vital imaging, pressure
      myography, and mathematical modeling. Collagenase and elastase digestions were
      applied to evaluate the load-bearing roles of collagen and elastin, respectively.
      The incremental elastic modulus linearly related to the straightness of
      adventitial collagen fibers circumferentially and longitudinally (both R2 >=
      0.99), whereas there was a nonlinear relationship to the internal elastic lamina
      elastin fiber branching angles. Mathematical modeling suggested a collagen
      recruitment strain (means +/- SE) of 1.1 +/- 0.2 circumferentially and 0.20 +/-
      0.01 longitudinally, corresponding to a pressure of ~40 mmHg, a finding supported
      by the vital imaging. The integrated method was tested on human PRA to confirm
      its validity. These showed limited circumferential distensibility and elongation
      and a collagen recruitment strain of 0.8 +/- 0.1 circumferentially and 0.06 +/-
      0.02 longitudinally, reached at a distending pressure below 20 mmHg. This was
      confirmed by vital imaging showing negligible microarchitectural changes of
      elastin and collagen upon pressurization. In conclusion, we show here, for the
      first time in resistance arteries, a quantitative relationship between pressure
      induced changes in the extracellular matrix and the arterial wall mechanics. The
      strength of the integrated methods invites for future detailed studies of
      microvascular pathologies.NEW & NOTEWORTHY This is the first study to
      quantitatively relate pressure-induced microstructural changes in resistance
      arteries to the mechanics of their wall. Principal findings using a pig model
      system were confirmed in human arteries. The combined methods provide a strong
      tool for future hypothesis-driven studies of microvascular pathologies.

PMID- 28432058
TI  - MK5 haplodeficiency attenuates hypertrophy and preserves diastolic function
      during remodeling induced by chronic pressure overload in the mouse heart.
AB  - MAPK-activated protein kinase-5 (MK5) is a protein serine/threonine kinase that
      is activated by p38 MAPK and the atypical MAPKs ERK3 and ERK4. The physiological
      function(s) of MK5 remains unknown. Here, we examined the effect of MK5
      haplodeficiency on cardiac function and myocardial remodeling. At 12 wk of age,
      MK5 haplodeficient mice (MK5+/-) were smaller than age-matched wild-type
      littermates (MK5+/+), with similar diastolic function but reduced systolic
      function. Transverse aortic constriction (TAC) was used to induce chronic
      pressure overload in 12-wk-old male MK5+/- and MK5+/+ mice. Two weeks post-TAC,
      heart weight-to-tibia length ratios were similarly increased in MK5+/- and MK5+/+
      hearts, as was the abundance of B-type natriuretic peptide and beta-myosin heavy
      chain mRNA. Left ventricular ejection fraction was reduced in both MK5+/+ and
      MK5+/- mice, whereas regional peak systolic tissue velocities were reduced and
      isovolumetric relaxation time was prolonged in MK5+/+ hearts but not in MK5+/-
      hearts. The TAC-induced increase in collagen type 1-alpha1 mRNA observed in
      MK5+/+ hearts was markedly attenuated in MK5+/- hearts. Eight weeks post-TAC,
      systolic function was equally impaired in MK5+/+ and MK5+/- mice. In contrast,
      the increase in E wave deceleration rate and progression of hypertrophy observed
      in TAC MK5+/+ mice were attenuated in TAC MK5+/- mice. MK5 immunoreactivity was
      detected in adult fibroblasts but not in myocytes. MK5+/+, MK5+/-, and MK5-/-
      fibroblasts all expressed alpha-smooth muscle actin in culture. Hence, reduced
      MK5 expression in cardiac fibroblasts was associated with the attenuation of both
      hypertrophy and development of a restrictive filling pattern during myocardial
      remodeling in response to chronic pressure overload.NEW & NOTEWORTHY MAPK
      activated protein kinase-5 (MK5)/p38-regulated/activated protein kinase is a
      protein serine/threonine kinase activated by p38 MAPK and/or the atypical MAPKs
      ERK3 and ERK4. MK5 immunoreactivity was detected in adult ventricular fibroblasts
      but not in myocytes. MK5 haplodeficiency attenuated the progression of
      hypertrophy, reduced collagen type 1 mRNA, and protected diastolic function in
      response to chronic pressure overload.

PMID- 28432059
TI  - Increased amplitude of inward rectifier K+ currents with advanced age in smooth
      muscle cells of murine superior epigastric arteries.
AB  - Inward rectifier K+ channels (KIR) may contribute to skeletal muscle blood flow
      regulation and adapt to advanced age. Using mouse abdominal wall superior
      epigastric arteries (SEAs) from either young (3-6 mo) or old (24-26 mo) male
      C57BL/6 mice, we investigated whether SEA smooth muscle cells (SMCs) express
      functional KIR channels and how aging may affect KIR function. Freshly dissected
      SEAs were either enzymatically dissociated to isolate SMCs for
      electrophysiological recording (perforated patch) and mRNA expression or used
      intact for pressure myography. With 5 mM extracellular K+ concentration ([K+]o),
      exposure of SMCs to the KIR blocker Ba2+ (100 MUM) had no significant effect (P >
      0.05) on whole cell currents elicited by membrane potentials spanning -120 to -30
      mV. Raising [K+]o to 15 mM activated Ba2+-sensitive KIR currents between -120 and
      -30 mV, which were greater in SMCs from old mice than in SMCs from young mice (P
      < 0.05). Pressure myography of SEAs revealed that while aging decreased maximum
      vessel diameter by ~8% (P < 0.05), it had no significant effect on resting
      diameter, myogenic tone, dilation to 15 mM [K+]o, Ba2+-induced constriction in 5
      mM [K+]o, or constriction induced by 15 mM [K+]o in the presence of Ba2+ (P >
      0.05). Quantitative RT-PCR revealed SMC expression of KIR2.1 and KIR2.2 mRNA that
      was not affected by age. Barium-induced constriction of SEAs from young and old
      mice suggests an integral role for KIR in regulating resting membrane potential
      and vasomotor tone. Increased functional expression of KIR channels during
      advanced age may compensate for other age-related changes in SEA function.NEW &
      NOTEWORTHY Ion channels are integral to blood flow regulation. We found greater
      functional expression of inward rectifying K+ channels in smooth muscle cells of
      resistance arteries of mouse skeletal muscle with advanced age. This adaptation
      to aging may contribute to the maintenance of vasomotor tone and blood flow
      regulation during exercise.

PMID- 28432061
TI  - Terence J Wilkin.

PMID- 28432060
TI  - Toll-like receptor 2 dominance over Toll-like receptor 4 in stressful conditions
      for its detrimental role in the heart.
AB  - It has been suggested that Toll-like receptor (TLR)4 promotes IL-10-mediated
      cardiac cell survival, whereas another receptor, TLR2, from the same family, is
      detrimental. Here, we examined the interactive role of these two innate signaling
      molecules under stressful conditions, including IL-10 knockout (IL-10-/-) mice,
      global ischemia-reperfusion (I/R) injury in rat hearts, and in vitro short
      hairpin RNA experimental models in the presence or absence of IL-10 (10 ng/ml).
      Circulating and myocardial levels of TNF-alpha as well as apoptosis and fibrosis
      were higher in IL-10-/- mice. The increase in TLR2 in IL-10-/- hearts indicated
      its negative regulation by IL-10. Ex vivo I/R also caused a marked upregulation
      of TLR2 and TNF-alpha as well as apoptotic and fibrotic signals. However, a 40
      min reperfusion with IL-10 triggered an increase in TLR4 expression and improved
      recovery of cardiac function. The increase in IL-1 receptor-associated kinase
      (IRAK)-M and IRAK-2 activity during I/R injury suggested their role in TLR2
      signaling. In vitro inhibition of TLR4 activity as a consequence of RNA
      inhibition-mediated suppression of myeloid differentiation gene (MyD)88 suggested
      MyD88-dependent activation of TLR4. The inclusion of IL-10 during reperfusion
      also downregulated the expression of IRAK-2, TNF-alpha receptor-associated factor
      1-interacting protein (TRAIP) and apoptotic signals, caspase-3, and the Bax-to
      Bcl-xL ratio. IL-10 reduced the TNF-alpha receptor-associated increase in TRAIP
      induced apoptosis during I/R injury, which led to an increase in IL-1beta to
      mitigate transforming growth factor-beta receptor type I-mediated fibrosis. The
      IL-10 mitigation of these changes suggests that the stimulation through TLR4
      signaling promotes IRAK-4 and phosphorylates IRAK-1 instead of IRAK-2 and may be
      an important therapeutic approach in restoring heart health in stress.NEW &
      NOTEWORTHY Under stress conditions such as downregulation of the IL-10 gene or
      ischemia-reperfusion injury, Toll-like receptor (TLR)4 and IL-1 receptor
      associated kinase (IRAK)-1 activation is suppressed, along with the upregulation
      of TLR-2 and IRAK-2, resulting in fibrosis and apoptosis. It is suggested that IL
      10 helps to maintain heart function during stress via myeloid differentiation
      gene 88/IRAK-4/IRAK-1-dependent TLR4 signaling.

PMID- 28432062
TI  - Consultant productivity depends on investment in the system and support staff.

PMID- 28432063
TI  - A realist review to explore how low-income pregnant women use food vouchers from
      the UK's Healthy Start programme.
AB  - OBJECTIVES: To explore how low-income pregnant women use Healthy Start food
      vouchers, the potential impacts of the programme, and which women might
      experience these impacts and why. DESIGN: A realist review. ELIGIBILITY CRITERIA
      FOR SELECTING STUDIES: Primary or empirical studies (of any design) were included
      if they contributed relevant evidence or insights about how low-income women use
      food vouchers from the Healthy Start (UK) or the Special Supplemental Nutrition
      Program for Women, Infants and Children (WIC) programmes. The assessment of
      'relevance' was deliberately broad to ensure that reviewers remained open to new
      ideas from a variety of sources of evidence. ANALYSIS: A combination of evidence
      synthesis and realist analysis techniques was used to modify, refine and
      substantiate programme theories, which were constructed as explanatory 'context
      mechanism-outcome'-configurations. RESULTS: 38 primary studies were included in
      this review: four studies on Healthy Start and 34 studies on WIC. Two main
      outcome strands were identified: dietary improvements (intended) and financial
      assistance (unintended). Three evidence-informed programme theories were proposed
      to explain how aspects of context (and mechanisms) may generate these outcomes:
      the 'relative value' of healthy eating (prioritisation of resources); retailer
      discretion (pressure to 'bend the rules'); the influence of other family members
      (disempowerment). CONCLUSIONS: This realist review suggests that some low-income
      pregnant women may use Healthy Start vouchers to increase their consumption of
      fruits and vegetables and plain cow's milk, whereas others may use them to reduce
      food expenditure and save money for other things.

PMID- 28432071
TI  - John Davies.

PMID- 28432064
TI  - The prevalence of acne in Mainland China: a systematic review and meta-analysis.
AB  - INTRODUCTION: Acne, a very common skin disease, can result in psychological
      distress and sustain impairment in quality of life. Data on the prevalence of
      acne and the differences in gender, region and age are limited. The aim of this
      review is to estimate the prevalence of acne in Mainland China comprehensively
      and to quantify its association with gender, region and age. METHODS: We searched
      electronic databases with predetermined search terms to identify relevant studies
      published between 1 January 1996 and 30 September 2016. We pointed out repeated
      results using Note Express software and evaluated the studies for inclusion. Two
      independent reviewers extracted the data, followed with statistical analyses
      using Comprehensive Meta-Analysis software version 2.0. A random effects model
      was adopted to calculate the overall pooled prevalence and to merge categories,
      including gender (males and females), region (Northern China and Southern China)
      and age (primary and secondary students: 7-17 years old; undergraduates: 18-23
      years old; overall: no limits of age) for subgroup analyses. Logistic meta
      regression analysis was used to clarify the associations between acne and the
      predictors age, gender and region using OR and their associated 95% CI. RESULTS:
      25 relevant studies were included in this meta-analysis. The overall pooled
      prevalence rates of acne were 39.2% (95% CI 0.310 to 0.479). The prevalence rates
      in different age groups were 10.2% overall (95% CI 0.059 to 0.171), 50.2% for
      primary and secondary students (95% CI 0.451 to 0.554), and 44.5% for
      undergraduates (95% CI 0.358 to 0.534); by gender, the prevalence rates were
      35.7% for females (95% CI 0.275 to 0.448) and 39.7% for males (95% CI 0.317 to
      0.482); and by region, the prevalence rates were 34.2% for Northern China (95% CI
      0.242 to 0.458) and 46.3% for Southern China (95% CI 0.374 to 0.555). The
      associations between acne and the predictors age, gender and region were
      statistically significant. CONCLUSIONS: In Mainland China, primary and secondary
      students exhibited higher prevalence rates than undergraduate students; males had
      higher prevalence rates of acne than females; and the prevalence rates of acne in
      Southern China was higher than Northern China.

PMID- 28432072
TI  - Translocase of Inner Membrane 50 Functions as a Novel Protective Regulator of
      Pathological Cardiac Hypertrophy.
AB  - BACKGROUND: Translocase of inner membrane 50 (TIM50) is a member of the
      translocase of inner membrane (TIM) complex in the mitochondria. Previous
      research has demonstrated the role of TIM50 in the regulation of oxidative stress
      and cardiac morphology. However, the role of TIM50 in pathological cardiac
      hypertrophy remains unknown. METHODS AND RESULTS: In the present study we found
      that the expression of TIM50 was downregulated in hypertrophic hearts. Using
      genetic loss-of-function animal models, we demonstrated that TIM50 deficiency
      increased heart and cardiomyocyte size with more severe cardiac fibrosis compared
      with wild-type littermates. Moreover, we generated cardiomyocyte-specific TIM50
      transgenic mice in which the hypertrophic and fibrotic phenotypes were all
      alleviated. Next, we tested reactive oxygen species generation and the activities
      of the antioxidant enzymes superoxide dismutase and catalase, and also
      respiratory chain complexes I, II, and IV, finding that all the activities were
      regulated by TIM50. Meanwhile, expression of the ASK1-JNK/P38 axis was increased
      in TIM50-deficient mice, and TIM50 overexpression decreased the activity of the
      ASK1-JNK/P38 axis. Finally, we treated mice with the antioxidant N-acetyl
      cysteine to reduce oxidative stress. After N-acetyl cysteine treatment, the
      deteriorative hypertrophic and fibrotic phenotypes caused by TIM50 deficiency
      were all remarkably reversed. CONCLUSIONS: These data indicated that TIM50 could
      attenuate pathological cardiac hypertrophy primarily by reducing oxidative
      stress. TIM50 could be a promising target for the prevention and therapy of
      cardiac hypertrophy and heart failure.

PMID- 28432073
TI  - In Situ Laser Fenestration Is a Feasible Method for Revascularization of Aortic
      Arch During Thoracic Endovascular Aortic Repair.
AB  - BACKGROUND: Reconstruction of the aortic major branches during thoracic
      endovascular aortic repair is complicated because of the complex anatomic
      configuration and variation of the aortic arch. In situ laser fenestration has
      shown great potential for the revascularization of aortic branches. This study
      aims to evaluate the feasibility, effectiveness, and safety of in situ laser
      fenestration on the three branches of the aortic arch during thoracic
      endovascular aortic repair. METHODS AND RESULTS: Before clinical application, the
      polytetrafluoroethylene and Dacron grafts were fenestrated by an 810-nm laser
      system ex vivo, which did not damage the bare metal portion of the endografts and
      created a clean fenestration while maintaining the integrity of the endografts.
      In vivo, 6 anesthetized female swine survived after this operation, including
      stent-graft implantation in the aortic arches, laser fenestration, and conduit
      implantation through the innominate arteries and the left carotid arteries. Based
      on the animal experiments, in situ laser fenestration during thoracic
      endovascular aortic repair was successively performed on 24 patients (aged 33-86
      years) with aortic artery diseases (dissection type A: n=4, type B: n=7,
      aneurysm: n=2, mural thrombus: n=7). Fenestration of 3 aortic branches was
      performed in 2 (8.3%) patients. Both the left carotid artery and the left
      subclavian artery were fenestrated in 6 (25%) patients. Only left subclavian
      artery fenestration surgery was done in 16 (66.7%) patients. Among these
      patients, 1 fenestration was abandoned secondary to an acute takeoff of the
      innominate artery in a type III aortic arch. The average operative time was 137+/
      15 minutes. The technical success rate was 95.8% (n=23). No fenestration-related
      complications or neurological morbidity occurred after this operation. During a
      mean postoperative 10-month follow-up (range: 2-17 months), 1 patient died of
      severe pneumonia, and all the left subclavian artery and carotid artery stents
      were patent with no fenestration-related endoleaks upon computed tomography
      angiography images. CONCLUSIONS: In situ laser fenestration is a feasible,
      effective, rapid, repeatable, and safe option for the reconstruction of aortic
      arch during thoracic endovascular aortic repair, which might be available to
      revascularize the 3 branches. However, follow-up periods should be extended to
      evaluate the robustness of this technique.

PMID- 28432075
TI  - Suicidal thoughts and behaviours are influenced by many factors.

PMID- 28432074
TI  - Incidence of First Stroke in Pregnant and Nonpregnant Women of Childbearing Age:
      A Population-Based Cohort Study From England.
AB  - BACKGROUND: Pregnant women may have an increased risk of stroke compared with
      nonpregnant women of similar age, but the magnitude and the timing of such risk
      are unclear. We examined the risk of a first stroke event in women of
      childbearing age and compared the risk during pregnancy and in the early
      postpartum period with the background risk outside these periods. METHODS AND
      RESULTS: We conducted an open cohort study of 2 046 048 women aged 15 to 49 years
      between April 1, 1997, and March 31, 2014, using linked primary (Clinical
      Practice Research Datalink) and secondary (Hospital Episode Statistics) care
      records in England. Risk of first stroke was assessed by calculating the
      incidence rate of stroke in antepartum, peripartum (2 days before until 1 day
      after delivery), and early (first 6 weeks) and late (second 6 weeks) postpartum
      periods compared with nonpregnant time using a Poisson regression model with
      adjustment for maternal age, socioeconomic group, and calendar time. A total of
      2511 women had a first stroke. The incidence rate of stroke was 25.0 per 100 000
      person-years (95% CI 24.0-26.0) in nonpregnant time. The rate was lower
      antepartum (10.7 per 100 000 person-years, 95% CI 7.6-15.1) but 9-fold higher
      peripartum (161.1 per 100 000 person-years, 95% CI 80.6-322.1) and 3-fold higher
      early postpartum (47.1 per 100 000 person-years, 95% CI 31.3-70.9). Rates of
      ischemic and hemorrhagic stroke both increased peripartum and early postpartum.
      CONCLUSIONS: Although the absolute risk of first stroke is low in women of
      childbearing age, healthcare professionals should be aware of a considerable
      increase in relative risk during the peripartum and early postpartum periods.

PMID- 28432076
TI  - Is lower hip range of motion a risk factor for groin pain in athletes? A
      systematic review with clinical applications.
AB  - BACKGROUND: Whether hip range of motion (ROM) is a risk factor for groin pain in
      athletes is not known. OBJECTIVES: To systematically review the relationship
      between hip ROM and groin pain in athletes in cross-sectional/case-control and
      prospective studies. STUDY DESIGN: Systematic review, prospectively registered
      (PROSPERO) according to PRISMA guidelines. METHODS: Pubmed, Embase, CINAHL and
      SPORTDiscus were systematically searched up to December 2015. Two authors
      performed study selection, data extraction/analysis, quality assessment (Critical
      Appraisal Skills Programme) and strength of evidence synthesis. RESULTS: We
      identified seven prospective and four case-control studies. The total quality
      score ranged from 29% to 92%. Heterogeneity in groin pain classification, injury
      definitions and physical assessment precluded data pooling. There was strong
      evidence that total rotation of both hips below 85 degrees  measured at the pre
      season screening was a risk factor for groin pain development. Strong evidence
      suggested that internal rotation, abduction and extension were not associated
      with the risk or presence of groin pain. CONCLUSION: Total hip ROM is the factor
      most consistently related to groin pain in athletes. Screening for hip ROM is
      unlikely to correctly identify an athlete at risk of developing groin pain
      because of the small ROM differences found and poor ROM measurement properties.

PMID- 28432077
TI  - Aerobic exercise promotes executive functions and impacts functional neural
      activity among older adults with vascular cognitive impairment.
AB  - BACKGROUND: Vascular cognitive impairment (VCI) results from cerebrovascular
      disease, and worldwide, it is the second most common type of cognitive
      dysfunction. While targeted aerobic training is a promising approach to delay the
      progression of VCI by reducing cardiometabolic risk factors, few randomised
      controlled trials to date have specifically assessed the efficacy of aerobic
      training on cognitive and brain outcomes in this group at risk for functional
      decline. AIM: To examine the effect of moderate-intensity aerobic training on
      executive functions and functional neural activity among older adults with mild
      subcortical ischaemic VCI (SIVCI). METHODS: Older adults with mild SIVCI were
      randomly assigned to: (1) 6-month, 3*/week aerobic training (n=10) or (2) usual
      care (control; n=11). Participants completed functional MRI (fMRI) at baseline
      and trial completion. During the fMRI sessions, behavioural performance on the
      Eriksen flanker task and task-evoked neural activity were assessed. RESULTS: At
      trial completion, after adjusting for baseline general cognition, total white
      matter lesion volume and flanker performance, compared with the control group,
      the aerobic training group significantly improved flanker task reaction time.
      Moreover, compared with the controls, the aerobic training group demonstrated
      reduced activation in the left lateral occipital cortex and right superior
      temporal gyrus. Reduced activity in these brain regions was significantly
      associated with improved (ie, faster) flanker task performance at trial
      completion. SUMMARY: Aerobic training among older adults with mild SIVCI can
      improve executive functions and neural efficiency of associated brain areas.
      Future studies with greater sample size should be completed to replicate and
      extend these findings.

PMID- 28432078
TI  - Effect of 4-[(5,6,7,8-Tetrahydro-5,5,8,8-Tetramethyl-2
      Naphthalenyl)Carbamoyl]Benzoic Acid (Am80) on Alveolar Regeneration in
      Adiponectin Deficient-Mice Showing a Chronic Obstructive Pulmonary Disease-Like
      Pathophysiology.
AB  - Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease
      that causes widespread and irreversible alveolar collapse. Although COPD occurs
      worldwide, only symptomatic therapy is currently available. Our objective is the
      development of therapeutic agents to eradicate COPD. Therefore, we focused on 4
      [(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid
      (Am80), which is a derivative of all-trans retinoic acid. We evaluated the
      effects of Am80 on alveolar repair in a novel COPD model of adiponectin-deficient
      mice. This mouse model has more symptoms similar to human COPD than the classic
      elastase-induced emphysema mouse model. Lung volume, computed tomography (CT)
      values, low-attenuation area ratios, and bone and fat mass were measured by CT.
      However, the administration of Am80 did not affect these results. To examine the
      degree of destruction in the alveoli, the mean linear intercept of the alveolar
      walls was calculated, and assessment of this value confirmed that there was a
      significant difference between the control (46.3 +/- 2.3 MUm) and 0.5 mg/kg Am80
      treated group (34.4 +/- 1.7 um). All mice survived the treatment, which lasted
      for more than 6 months, and we did not observe any abnormalities in autopsies
      performed at 80 weeks of age. These results suggested that Am80 was effective as
      a novel therapeutic compound for the treatment of COPD.

PMID- 28432079
TI  - Regulation of microtubule-associated motors drives intermediate filament network
      polarization.
AB  - Intermediate filaments (IFs) are key players in the control of cell morphology
      and structure as well as in active processes such as cell polarization,
      migration, and mechanoresponses. However, the regulatory mechanisms controlling
      IF dynamics and organization in motile cells are still poorly understood. In this
      study, we investigate the mechanisms leading to the polarized rearrangement of
      the IF network along the polarity axis. Using photobleaching and photoconversion
      experiments in glial cells expressing vimentin, glial fibrillary acidic protein,
      and nestin, we show that the distribution of cytoplasmic IFs results from a
      continuous turnover based on the cooperation of an actin-dependent retrograde
      flow and anterograde and retrograde microtubule-dependent transports. During
      wound-induced astrocyte polarization, IF transport becomes directionally biased
      from the cell center toward the cell front. Such asymmetry in the transport is
      mainly caused by a Cdc42- and atypical PKC-dependent inhibition of dynein
      dependent retrograde transport. Our results show how polarity signaling can
      affect the dynamic turnover of the IF network to promote the polarization of the
      network itself.

PMID- 28432081
TI  - Glucose tolerance and insulin responsiveness in Gitelman syndrome patients.
AB  - OBJECTIVE: Impaired glucose metabolism and insulin sensitivity have been reported
      in patients with Gitelman syndrome (GS), but insulin secretion and the related
      mechanisms are not well understood. DESIGN AND METHODS: The serum glucose levels,
      insulin secretion and insulin sensitivity were evaluated in patients with GS (n =
      28), patients with type 2 diabetes mellitus (DM) and healthy individuals (n = 20
      in both groups) using an oral glucose tolerance test. Serum and urine sodium,
      potassium and creatinine levels were measured at 0, 30, 60, 120 and 180 min after
      an oral glucose load was administered. RESULTS: The areas under the serum glucose
      curves were higher in the GS patients than those in the healthy controls (17.4 +/
      5.1 mmol.h/L vs 14.5 +/- 2.8 mmol.h/L, P = 0.02) but lower than those in the DM
      patients (24.8 +/- 5.3 mmol.h/L, P < 0.001). The areas under the serum insulin
      curves and the insulin secretion indexes in GS patients were higher than those in
      DM patients and lower than those in healthy subjects. The insulin secretion
      sensitivity index of GS patients was between that of healthy subjects and DM
      patients, but the insulin sensitivity indices were not different among the three
      groups. After one hour of glucose administration, the serum potassium level
      significantly decreased from baseline, and the urinary potassium-to-creatinine
      ratio increased gradually and peaked at 2 h. CONCLUSIONS: Glucose metabolism and
      insulin secretion were impaired in GS patients, but insulin sensitivity was
      comparable between GS patients and patients with type 2 DM. After administration
      of an oral glucose load, the plasma potassium level decreased in GS patients due
      to the increased excretion of potassium in the urine.

PMID- 28432080
TI  - NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus.
AB  - The PIDDosome (PIDD-RAIDD-caspase-2 complex) is considered to be the primary
      signaling platform for caspase-2 activation in response to genotoxic stress. Yet
      studies of PIDD-deficient mice show that caspase-2 activation can proceed in the
      absence of PIDD. Here we show that DNA damage induces the assembly of at least
      two distinct activation platforms for caspase-2: a cytoplasmic platform that is
      RAIDD dependent but PIDD independent, and a nucleolar platform that requires both
      PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1)
      acts as a scaffold for PIDD and is essential for PIDDosome assembly in the
      nucleolus after DNA damage. Inhibition of NPM1 impairs caspase-2 processing,
      apoptosis, and caspase-2-dependent inhibition of cell growth, demonstrating that
      the NPM1-dependent nucleolar PIDDosome is a key initiator of the caspase-2
      activation cascade. Thus we have identified the nucleolus as a novel site for
      caspase-2 activation and function.

PMID- 28432082
TI  - Effect of oral contraceptives and/or metformin on GLP-1 secretion and reactive
      hypoglycaemia in polycystic ovary syndrome.
AB  - CONTEXT: Insulin resistance in polycystic ovary syndrome (PCOS) may increase the
      risk of reactive hypoglycaemia (RH) and decrease glucagon-like peptide-1 (GLP-1)
      secretion. The possible effects of treatment with oral contraceptives (OCP)
      and/or metformin on GLP-1 secretion and risk of RH in PCOS is undetermined.
      SETTING: Outpatient clinic. PATIENTS AND INTERVENTIONS: Randomized, controlled
      clinical trial. Ninety women with PCOS were randomized to 12-month treatment with
      OCP (150 mg desogestrel + 30 mg ethinylestradiol), metformin (2 g/day) or
      metformin + OCP. Five-hour oral glucose tolerance tests (5-h OGTT) measuring
      fasting and area under the curve (AUC) for GLP-1, glucose, insulin and C-peptide
      were performed before and after the intervention period. Sixty-five women
      completed the study and 34 weight-matched healthy women were included as
      controls. MAIN OUTCOME MEASURES: Changes in GLP-1, glucose, insulin and C-peptide
      during 5-h OGTT. RESULTS: Fasting GLP-1 levels increased during metformin + OCP
      vs OCP treatment, whereas AUC GLP-1 levels were unchanged during medical
      treatment. The prevalence of reactive hypoglycemia increased from 9/65 to 14/65
      after intervention (P < 0.01) and was more common after treatment with metformin
      + OCP (increase from 3/23 to 6/23, P = 0.01). Reactive hypoglycaemia was
      associated with higher insulin and C-peptide levels during 5-h OGTT, but was
      unassociated with BMI and AUC GLP-1. GLP-1 levels were comparable in PCOS vs
      controls. AUC GLP-1 levels were significantly lower in obese vs lean patients and
      were inversely associated with BMI. CONCLUSIONS: AUC GLP-1 levels were unchanged
      during treatment. Increased risk of hypoglycemia during metformin + OCP could be
      associated with increased insulin secretion.

PMID- 28432083
TI  - Optimal CD4 T cell priming after LPS-based adjuvanticity with CD134 costimulation
      relies on CXCL9 production.
AB  - LPS is a powerful adjuvant, and although LPS-mediated TLR4 signaling has been
      exquisitely delineated, the in vivo mechanism of how TLR4 responses impact T cell
      priming is far less clear. Besides costimulation, TNF and type 1 IFN are dominant
      cytokines released after TLR4 activation and can shape T cell responses, but
      other downstream factors have not been examined extensively. Depending on
      context, we show that IFNalphaR1 blockade resulted in minor to major effects on
      specific CD4 T cell clonal expansion. To help explain these differences, it was
      hypothesized that IFNalphaR1 blockade would inhibit specific T cell migration by
      reducing chemokine receptor signaling, but specific CD4 T cells from IFNalphaR1
      blocked mice were readily able to migrate in response to specific chemokines.
      Next, we examined downstream factors and found that type 1 IFN signaling was
      necessary for chemokine production, even when mice were immunized with specific
      Ag with LPS and CD134 costimulation. IFNalphaR1 signaling promoted CXCL9 and
      CXCL10 synthesis, suggesting that these chemokines might be involved in the LPS
      and CD134 costimulation response. After immunization, we show that CXCL9 blockade
      inhibited CD4 T cell accumulation in the liver but also in LNs, even in the
      presence of elevated serum IFN-beta levels. Thus, whereas type 1 IFN might have
      direct effects on primed CD4 T cells, the downstream chemokines that play a role
      during migration also impact accumulation. In sum, CXCL9 production is a key
      benchmark for productive CD4 T cell vaccination strategies.

PMID- 28432084
TI  - Topoisomerase 2alpha and thymidylate synthase expression in adrenocortical
      cancer.
AB  - Topoisomerase II alpha (TOP2A) and thymidylate synthase (TS) are known prognostic
      parameters in several tumors and also predictors of efficacy of anthracyclines,
      topoisomerase inhibitors and fluoropirimidines, respectively. Expression of TOP2A
      and TS mRNA was assessed in 98 patients with adrenocortical carcinoma (ACC) and
      protein expression was assessed by immunohistochemistry in a subset of 39 tumors.
      Ninety-two patients were radically resected for stage II-III disease and 38 of
      them received adjuvant mitotane. Twenty-six patients with metastatic disease
      received the EDP-M (etoposide, doxorubicin, Adriamycin, cisplatin plus mitotane).
      TOP2A and TS expression in ACC tissue was directly correlated with the clinical
      data. Both markers were not associated with either disease free survival (DFS) or
      overall survival (OS) in multivariate analyses and failed to be associated to
      mitotane efficacy. Disease response or stabilization to EDP-M treatment was
      observed in 12/17 (71%) and 1/9 (11%) patients with high and low TOP2A expressing
      tumors (P = 0.0039) and 9/13 (69%) and 4/13 (31%) patients with high and low TS
      expressing ACC, respectively (P = 0.049). High TOP2A expression was significantly
      associated with longer time to progression (TTP) after EDP-M. TOP2A and TS
      proteins assessed by immunohistochemistry significantly correlated with mRNA
      expression. Immunohistochemical TOP2A expression was associated with a non
      significant better response and longer TTP after EDP-M. TOP2A and TS were neither
      prognostic nor predictive of mitotane efficacy in ACC patients. The predictive
      role of TOP2A expression of EDP-M activity suggests a significant contribution of
      Adriamycin and etoposide for the efficacy of the EDP scheme.

PMID- 28432085
TI  - Acute myeloid leukaemia in a case with Tatton-Brown-Rahman syndrome: the peculiar
      DNMT3A R882 mutation.
AB  - BACKGROUND: Recently a novel syndromic form of overgrowth with intellectual
      disability and distinct facial features was identified caused by constitutional
      mutations in the epigenetic regulator DNA-methyltransferase 3A (DNMT3A), referred
      to as Tatton-Brown-Rahman syndrome (TBRS). Somatically acquired mutations in
      DNMT3A occur in haematological malignancies and are frequently present in acute
      myeloid leukaemia (AML) affecting in more than 50% the arginine residue at
      position 882 (R882). To date, additional cases with TBRS have been published but
      so far none of the reported cases with TBRS developed AML. METHODS AND RESULTS:
      Here we present the first case of TBRS who developed AML at the age of 15 years.
      Whole-exome sequencing identified a constitutional heterozygous DNMT3A R882C
      mutation. Our case exhibits macrocephaly, intellectual disability, distinct
      facial dysmorphism and other recurrent features fitting with the TBRS phenotype.
      The AML of the myelomonocytic subtype harboured only few additional somatically
      acquired mutations, that is, an aberrant karyotype and a recurrent PTPN11
      mutation. DISCUSSION: The peculiarity of the specific R882 mutation in contrast
      to other DNMT3A mutations is discussed, including the hypothesis of the more
      aggressive nature of this variant.Our case represents the first evidence of the
      possible increased risk of the development of haematological malignancies in
      particular AML in cases with TBRS.

PMID- 28432086
TI  - Comparing two regimens of intravaginal misoprostol with intravaginal gemeprost
      for second-trimester pregnancy termination: a randomised controlled trial.
AB  - AIM: To compare the efficacy and safety of intravaginal misoprostol 200 ug, 400
      ug and gemeprost regimens for second-trimester termination of pregnancy (TOP).
      METHODS: A three- armed randomi sed controlled trial (Clinical Trial Certificate
      1100015) where 116 women undergoing second-trimester TOP were given intravaginal
      misoprostol 200 u g (n=37), misoprostol 400 ug (n=40) or gemeprost 1 mg (n=39) at
      4- hour intervals until abortion occurred with a maximum of five doses. RESULTS:
      The misoprostol 400 ug group had the highest incidence of successful abortions
      (92.5%) compared to the misoprostol 200 ug (70.3%; p=0.017) and gemeprost 1 mg
      (74.4%; p=0.037) within 48 hours. There was no significant difference in abortion
      rate between misoprostol 200 ug and gemeprost. The misoprostol 400 ug group had
      the highest incidence of fever (70.0%) compared to misoprostol 200 ug (24.3%;
      p<0.001) and gemeprost 1 mg (46.2%; p=0.041). The gemeprost group had the highest
      incidence of diarrhoea (38.5%) compared to misoprostol 400 ug (10.0%; p=0.004)
      and misoprostol 200 ug (8.1%; p=0.003) groups. CONCLUSIONS: Intravaginal
      misoprostol 400 u g at 4- hour intervals was the most effective regimen but was
      associated with a high incidence of fever. Misoprostol 200 ug demonstrated
      similar effectiveness as gemeprost and had lower incidence of diarrhoea.
      Gemeprost should not be first line for medical therapy given the cost, storage
      requirements and lower efficacy.

PMID- 28432087
TI  - Erratum. Diabetic Retinopathy: A Position Statement by the American Diabetes
      Association. Diabetes Care 2017;40:412-418.

PMID- 28432088
TI  - GPs and paediatric oncology palliative care: a Q methodological study.
AB  - OBJECTIVE: This mixed-methods study set in the West Midlands region of the UK
      demonstrates the effectiveness of Q methodology in examining general
      practitioners' (GPs') perception of their role in children's oncology palliative
      care. METHODS: Using data obtained from the analysis of semistructured interviews
      with GPs who had cared for a child receiving palliative care at home and bereaved
      parents, 50 statements were identified as representative of the analysis
      findings. 32 GPs with a non-palliative child with cancer on their caseload were
      asked to rank the statements according to their level of agreement/disagreement
      on a grid. They were then asked to reflect and comment on the statements they
      most and least agreed with. The data were analysed using a dedicated statistical
      software package for Q analysis PQMethod V.2.20 (Schmolck 2012). A centroid
      factor analysis was undertaken initially with 7 factors then repeated for factors
      1-6. Varimax and manual flagging was then completed. RESULTS: 4 shared viewpoints
      were identified denoting different GP roles: the GP, the compassionate
      practitioner, the team player practitioner and the pragmatic practitioner. In
      addition consensus (time pressures, knowledge deficits, emotional toll) and
      disagreement (psychological support, role, experiential learning, prior
      relationships) between the viewpoints were identified and examined. CONCLUSIONS:
      Q methodology, used for the first time in this arena, identified 4 novel and
      distinct viewpoints reflecting a diverse range of GP perspectives. Appropriately
      timed and targeted GP education, training, support, in conjunction with
      collaborative multiprofessional working, have the potential to inform their role
      and practice across specialities.

PMID- 28432089
TI  - Preparing future doctors for palliative care: views of course organisers.
AB  - BACKGROUND: Effective training at medical school is essential to prepare new
      doctors to safely manage patients with palliative care (PC) and end of life care
      (EOLC) needs. The contribution of undergraduate PC course organisers is central
      but their collective views regarding role are unknown. OBJECTIVE: To survey
      attitudes of PC course organisers regarding their course, organisation, the
      adequacy of training provided and level of personal satisfaction. METHODS: An
      anonymised, multifactorial, web-based questionnaire was devised, tested, modified
      and then sent to lead PC course organisers at all UK medical schools. RESULTS:
      Data were obtained from all 30 UK medical schools. Organisers agreed/strongly
      agreed (=agreed) that their PC course was highly rated by students (26, 87%). 25
      (83%) agreed their course 'enabled misconceptions and fears about PC, death,
      dying and bereavement to be addressed', 'delivered quality PC training' (23,
      77%), 'fulfilled General Medical Council requirements' (19, 63%), 'prepared
      students well to care for patients with PC/EOLC needs' (18, 60%) and 'enabled
      students to visit a hospice and see the role of doctors in caring for the dying'
      (17, 57%). Concerns were limited capacity to accommodate students (agreed 20,
      66%) and variability in teaching according to location (15, 50%). Most agreed
      their institution recognised PC training as important (22, 73%), they felt
      supported by colleagues (21, 70%) and experienced cooperation between
      stakeholders (20, 67%). All agreed that PC training was essential for
      undergraduates, while 29 (97%) supported inclusion of a hospice visit in the
      curriculum. 27 agreed that their role was satisfying (90%), 3 disagreed (10%).
      CONCLUSIONS: Approximately two-thirds of organisers were generally positive about
      their PC course, institution and role. A minority expressed concerns; these may
      reflect suboptimal PC training at their medical school and poor preparation of
      new doctors.

PMID- 28432090
TI  - International variations in clinical practice guidelines for palliative sedation:
      a systematic review.
AB  - OBJECTIVES: Palliative sedation is a highly debated medical practice,
      particularly regarding its proper use in end-of-life care. Worldwide, guidelines
      are used to standardise care and regulate this practice. In this review, we
      identify and compare national/regional clinical practice guidelines on palliative
      sedation against the European Association for Palliative Care (EAPC) palliative
      sedation Framework and assess the developmental quality of these guidelines using
      the Appraisal Guideline Research and Evaluation (AGREE II) instrument. METHODS:
      Using the PRISMA criteria, we searched multiple databases (PubMed, CancerLit,
      CINAHL, Cochrane Library, NHS Evidence and Google Scholar) for relevant
      guidelines, and selected those written in English, Dutch and Italian; published
      between January 2000 and March 2016. RESULTS: Of 264 hits, 13 guidelines-Belgium,
      Canada (3), Ireland, Italy, Japan, the Netherlands, Norway, Spain, Europe, and
      USA (2) were selected. 8 contained at least 9/10 recommendations published in the
      EAPC Framework; 9 recommended 'pre-emptive discussion of the potential role of
      sedation in end-of-life care'; 9 recommended 'nutrition/hydration while
      performing sedation' and 8 acknowledged the need to 'care for the medical team'.
      There were striking differences in terminologies used and in life expectancy
      preceding the practice. Selected guidelines were conceptually similar, comparing
      closely to the EAPC Framework recommendations, albeit with notable variations.
      CONCLUSIONS: Based on AGREE II, 3 guidelines achieved top scores and could
      therefore be recommended for use in this context. Also, domains 'scope and
      purpose' and 'editorial independence' ranked highest and lowest, respectively
      underscoring the importance of good reportage at the developmental stage.

PMID- 28432091
TI  - Follicular expression of pro-inflammatory cytokines tumour necrosis factor-alpha
      (TNFalpha), interleukin 6 (IL6) and their receptors in cattle: TNFalpha, IL6 and
      macrophages suppress thecal androgen production in vitro.
AB  - Pro-inflammatory cytokines secreted by macrophages and other cell types are
      implicated as intraovarian factors affecting different aspects of ovarian
      function including follicle and corpus luteum 'turnover', steroidogenesis and
      angiogenesis. Here, we compared granulosal (GC) and thecal (TC) expression of
      TNF, IL6 and their receptors (TNFRSF1A, TNFRSF1B and IL6R) during bovine antral
      follicle development; all five mRNA transcripts were detected in both GC and TC
      and statistically significant cell-type and follicle stage-related differences
      were evident. Since few studies have examined cytokine actions on TC
      steroidogenesis, we cultured TC under conditions that retain a non-luteinized
      'follicular' phenotype and treated them with TNFalpha and IL6 under basal and LH
      stimulated conditions. Both TNFalpha and IL6 suppressed androgen secretion
      concomitantly with CYP17A1 and LHCGR mRNA expression. In addition, TNFalpha
      reduced INSL3, HSD3B1 and NOS3 expression but increased NOS2 expression. IL6 also
      reduced LHCGR and STAR expression but did not affect HSD3B1, INSL3, NOS2 or NOS3
      expression. As macrophages are a prominent source of these cytokines in vivo, we
      next co-cultured TC with macrophages and observed an abolition of LH-induced
      androgen production accompanied by a reduction in CYP17A1, INSL3, LHCGR, STAR,
      CYP11A1 and HSD3B1 expression. Exposure of TC to bacterial lipopolysaccharide
      also blocked LH-induced androgen secretion, an effect reduced by a toll-like
      receptor blocker (TAK242). Collectively, the results support an inhibitory action
      of macrophages on thecal androgen production, likely mediated by their secretion
      of pro-inflammatory cytokines that downregulate the expression of LHCGR, CYP17A1
      and INSL3. Bovine theca interna cells can also detect and respond directly to
      lipopolysaccharide.

PMID- 28432092
TI  - Genome-Wide Investigation of Biofilm Formation in Bacillus cereus.
AB  - Bacillus cereus is a soil-dwelling Gram-positive bacterium capable of forming
      structured multicellular communities, or biofilms. However, the regulatory
      pathways controlling biofilm formation are less well understood in B. cereus In
      this work, we developed a method to study B. cereus biofilms formed at the air
      liquid interface. We applied two genome-wide approaches, random transposon
      insertion mutagenesis to identify genes that are potentially important for
      biofilm formation, and transcriptome analyses by RNA sequencing (RNA-seq) to
      characterize genes that are differentially expressed in B. cereus when cells were
      grown in a biofilm-inducing medium. For the first approach, we identified 23
      genes whose disruption by transposon insertion led to altered biofilm phenotypes.
      Based on the predicted function, they included genes involved in processes such
      as nucleotide biosynthesis, iron salvage, and antibiotic production, as well as
      genes encoding an ATP-dependent protease and transcription regulators.
      Transcriptome analyses identified about 500 genes that were differentially
      expressed in cells grown under biofilm-inducing conditions. One particular set of
      those genes may contribute to major metabolic shifts, leading to elevated
      production of small volatile molecules. Selected volatile molecules were shown to
      stimulate robust biofilm formation in B. cereus Our studies represent a genome
      wide investigation of B. cereus biofilm formation.IMPORTANCE In this work, we
      established a robust method for B. cereus biofilm studies and applied two genome
      wide approaches, transposon insertion mutagenesis and transcriptome analyses by
      RNA-seq, to identify genes and pathways that are potentially important for
      biofilm formation in B. cereus We discovered dozens of genes and two major
      metabolic shifts that seem to be important for biofilm formation in B. cereus Our
      study represents a genome-wide investigation on B. cereus biofilm formation.

PMID- 28432093
TI  - Diversity of Integrative and Conjugative Elements of Streptococcus salivarius and
      Their Intra- and Interspecies Transfer.
AB  - Integrative and conjugative elements (ICEs) are widespread chromosomal mobile
      genetic elements which can transfer autonomously by conjugation in bacteria.
      Thirteen ICEs with a conjugation module closely related to that of ICESt3 of
      Streptococcus thermophilus were characterized in Streptococcus salivarius by
      whole-genome sequencing. Sequence comparison highlighted ICE evolution by
      shuffling of 3 different integration/excision modules (for integration in the 3'
      end of the fda, rpsI, or rpmG gene) with the conjugation module of the ICESt3
      subfamily. Sequence analyses also pointed out a recombination occurring at oriT
      (likely mediated by the relaxase) as a mechanism of ICE evolution. Despite a
      similar organization in two operons including three conserved genes, the
      regulation modules show a high diversity (about 50% amino acid sequence
      divergence for the encoded regulators and presence of unrelated additional genes)
      with a probable impact on the regulation of ICE activity. Concerning the
      accessory genes, ICEs of the ICESt3 subfamily appear particularly rich in
      restriction-modification systems and orphan methyltransferase genes. Other cargo
      genes that could confer a selective advantage to the cell hosting the ICE were
      identified, in particular, genes for bacteriocin synthesis and cadmium
      resistance. The functionality of 2 ICEs of S. salivarius was investigated.
      Autonomous conjugative transfer to other S. salivarius strains, to S.
      thermophilus, and to Enterococcus faecalis was observed. The analysis of the ICE
      fda border sequence in these transconjugants allowed the localization of the DNA
      cutting site of the ICE integrase.IMPORTANCE The ICESt3 subfamily of ICEs appears
      to be widespread in streptococci and targets diverse chromosomal integration
      sites. These ICEs carry diverse cargo genes that can confer a selective advantage
      to the host strain. The maintenance of these mobile genetic elements likely
      relies in part on self-encoded restriction-modification systems. In this study,
      intra- and interspecies transfer was demonstrated for 2 ICEs of S. salivarius
      Closely related ICEs were also detected in silico in other Streptococcus species
      (S. pneumoniae and S. parasanguinis), thus indicating that diffusion of ICESt3
      related elements probably plays a significant role in horizontal gene transfer
      (HGT) occurring in the oral cavity but also in the digestive tract, where S.
      salivarius is present.

PMID- 28432094
TI  - Use of Synthetic Hybrid Strains To Determine the Role of Replicon 3 in Virulence
      of the Burkholderia cepacia Complex.
AB  - The Burkholderia cepacia complex (Bcc) displays a wealth of metabolic diversity
      with great biotechnological potential, but the utilization of these bacteria is
      limited by their opportunistic pathogenicity to humans. The third replicon of the
      Bcc, megaplasmid pC3 (0.5 to 1.4 Mb, previously chromosome 3), is important for
      various phenotypes, including virulence, antifungal, and proteolytic activities
      and the utilization of certain substrates. Approximately half of plasmid pC3 is
      well conserved throughout sequenced Bcc members, while the other half is not. To
      better locate the regions responsible for the key phenotypes, pC3 mutant
      derivatives of Burkholderia cenocepacia H111 carrying large deletions (up to 0.58
      Mb) were constructed with the aid of the FLP-FRT (FRT, flippase recognition
      target) recombination system from Saccharomyces cerevisiae The conserved region
      was shown to confer near-full virulence in both Caenorhabditis elegans and
      Galleria mellonella infection models. Antifungal activity was unexpectedly
      independent of the part of pC3 bearing a previously identified antifungal gene
      cluster, while proteolytic activity was dependent on the nonconserved part of
      pC3, which encodes the ZmpA protease. To investigate to what degree pC3-encoded
      functions are dependent on chromosomally encoded functions, we transferred pC3
      from Burkholderia cenocepacia K56-2 and Burkholderia lata 383 into other pC3
      cured Bcc members. We found that although pC3 is highly important for virulence,
      it was the genetic background of the recipient that determined the pathogenicity
      level of the hybrid strain. Furthermore, we found that important phenotypes, such
      as antifungal activity, proteolytic activity, and some substrate utilization
      capabilities, can be transferred between Bcc members using pC3.IMPORTANCE The
      Burkholderia cepacia complex (Bcc) is a group of closely related bacteria with
      great biotechnological potential. Some strains produce potent antifungal
      compounds and can promote plant growth or degrade environmental pollutants.
      However, their agricultural potential is limited by their opportunistic
      pathogenicity, particularly for cystic fibrosis patients. Despite much study,
      their virulence remains poorly understood. The third replicon, pC3, which is
      present in all Bcc isolates and is important for pathogenicity, stress
      resistance, and the production of antifungal compounds, has recently been
      reclassified from a chromosome to a megaplasmid. In this study, we identified
      regions on pC3 important for virulence and antifungal activity and investigated
      the role of the chromosomal background for the function of pC3 by exchanging the
      megaplasmid between different Bcc members. Our results may open a new avenue for
      the construction of antifungal but nonpathogenic Burkholderia hybrids. Such
      strains may have great potential as biocontrol strains for protecting fungus
      borne diseases of plant crops.

PMID- 28432095
TI  - Mushroom Emergence Detected by Combining Spore Trapping with Molecular
      Techniques.
AB  - Obtaining reliable and representative mushroom production data requires time
      consuming sampling schemes. In this paper, we assessed a simple methodology to
      detect mushroom emergence by trapping the fungal spores of the fruiting body
      community in plots where mushroom production was determined weekly. We compared
      the performance of filter paper traps with that of funnel traps and combined
      these spore trapping methods with species-specific quantitative real-time PCR and
      Illumina MiSeq to determine the spore abundance. Significantly more MiSeq
      proportional reads were generated for both ectomycorrhizal and saprotrophic
      fungal species using filter traps than were obtained using funnel traps. The
      spores of 37 fungal species that produced fruiting bodies in the study plots were
      identified. Spore community composition changed considerably over time due to the
      emergence of ephemeral fruiting bodies and rapid spore deposition (lasting from 1
      to 2 weeks), which occurred in the absence of rainfall events. For many species,
      the emergence of epigeous fruiting bodies was followed by a peak in the relative
      abundance of their airborne spores. There were significant positive relationships
      between fruiting body yields and spore abundance in time for five of seven fungal
      species. There was no relationship between fruiting body yields and their spore
      abundance at plot level, indicating that some of the spores captured in each plot
      were arriving from the surrounding areas. Differences in fungal detection
      capacity by spore trapping may indicate different dispersal ability between
      fungal species. Further research can help to identify the spore rain patterns for
      most common fungal species.IMPORTANCE Mushroom monitoring represents a serious
      challenge in economic and logistical terms because sampling approaches demand
      extensive field work at both the spatial and temporal scales. In addition, the
      identification of fungal taxa depends on the expertise of experienced fungal
      taxonomists. Similarly, the study of fungal dispersal has been constrained by
      technological limitations, especially because the morphological identification of
      spores is a challenging and time-consuming task. Here, we demonstrate that spores
      from ectomycorrhizal and saprotrophic fungal species can be identified using
      simple spore traps together with either MiSeq fungus-specific amplicon sequencing
      or species-specific quantitative real-time PCR. In addition, the proposed
      methodology can be used to characterize the airborne fungal community and to
      detect mushroom emergence in forest ecosystems.

PMID- 28432096
TI  - Interaction between 2,4-Diacetylphloroglucinol- and Hydrogen Cyanide-Producing
      Pseudomonas brassicacearum LBUM300 and Clavibacter michiganensis subsp.
      michiganensis in the Tomato Rhizosphere.
AB  - We have previously demonstrated that inoculation of tomato plants with 2,4
      diacetylphloroglucinol (DAPG)- and hydrogen cyanide (HCN)-producing Pseudomonas
      brassicacearum LBUM300 could significantly reduce bacterial canker symptoms
      caused by Clavibacter michiganensis subsp. michiganensis In this study, in order
      to better characterize the population dynamics of LBUM300 in the rhizosphere of
      tomato plants, we characterized the role played by DAPG and HCN production by
      LBUM300 on rhizosphere colonization of healthy and C. michiganensis subsp.
      michiganensis-infected tomato plants. The impact of C. michiganensis subsp.
      michiganensis presence on the expression of DAPG and HCN biosynthetic genes in
      the rhizosphere was also examined. In planta assays were performed using
      combinations of C. michiganensis subsp. michiganensis and wild-type LBUM300 or
      DAPG (LBUM300DeltaphlD) or HCN (LBUM300DeltahcnC) isogenic mutant strains.
      Populations of LBUM300 and phlD and hcnC gene expression levels were quantified
      in rhizosphere soil at several time points up to 264 h postinoculation using
      culture-independent quantitative PCR (qPCR) and reverse transcriptase
      quantitative PCR (RT-qPCR) TaqMan assays, respectively. The presence of C.
      michiganensis subsp. michiganensis significantly increased rhizospheric
      populations of LBUM300. In C. michiganensis subsp. michiganensis-infected tomato
      rhizospheres, the populations of wild-type LBUM300 and strain LBUM300DeltahcnC,
      both producing DAPG, were significantly higher than the population of strain
      LBUM300DeltaphlD A significant upregulation of phlD expression was observed in
      the presence of C. michiganensis subsp. michiganensis, while hcnC expression was
      only slightly increased in the mutant strain LBUM300DeltaphlD when C.
      michiganensis subsp. michiganensis was present. Additionally, biofilm production
      was found to be significantly reduced in strain LBUM300DeltaphlD compared to the
      wild-type and LBUM300DeltahcnC strains.IMPORTANCE The results of this study
      suggest that C. michiganensis subsp. michiganensis infection of tomato plants
      contributes to increasing rhizospheric populations of LBUM300, a biocontrol
      agent, as well as the overexpression of the DAPG biosynthetic operon in this
      bacterium. The increasing rhizospheric populations of LBUM300 represent one of
      the key factors in controlling C. michiganensis subsp. michiganensis in tomato
      plants, as DAPG-producing bacteria have shown the ability to decrease bacterial
      canker symptoms in tomato plants.

PMID- 28432097
TI  - Diazotrophic Growth Allows Azotobacter vinelandii To Overcome the Deleterious
      Effects of a glnE Deletion.
AB  - Overcoming the inhibitory effects of excess environmental ammonium on nitrogenase
      synthesis or activity and preventing ammonium assimilation have been considered
      strategies to increase the amount of fixed nitrogen transferred from bacterial to
      plant partners in associative or symbiotic plant-diazotroph relationships. The
      GlnE adenylyltransferase/adenylyl-removing enzyme catalyzes reversible
      adenylylation of glutamine synthetase (GS), thereby affecting the
      posttranslational regulation of ammonium assimilation that is critical for the
      appropriate coordination of carbon and nitrogen assimilation. Since GS is key to
      the sole ammonium assimilation pathway of Azotobacter vinelandii, attempts to
      obtain deletion mutants in the gene encoding GS (glnA) have been unsuccessful. We
      have generated a glnE deletion strain, thus preventing posttranslational
      regulation of GS. The resultant strain containing constitutively active GS is
      unable to grow well on ammonium-containing medium, as previously observed in
      other organisms, and can be cultured only at low ammonium concentrations. This
      phenotype is caused by the lack of downregulation of GS activity, resulting in
      high intracellular glutamine levels and severe perturbation of the ratio of
      glutamine to 2-oxoglutarate under excess-nitrogen conditions. Interestingly, the
      mutant can grow diazotrophically at rates comparable to those of the wild type.
      This observation suggests that the control of nitrogen fixation-specific gene
      expression at the transcriptional level in response to 2-oxoglutarate via NifA is
      sufficiently tight to alone regulate ammonium production at levels appropriate
      for optimal carbon and nitrogen balance.IMPORTANCE In this study, the
      characterization of the glnE knockout mutant of the model diazotroph Azotobacter
      vinelandii provides significant insights into the integration of the regulatory
      mechanisms of ammonium production and ammonium assimilation during nitrogen
      fixation. The work reveals the profound fidelity of nitrogen fixation regulation
      in providing ammonium sufficient for maximal growth but constraining
      energetically costly excess production. A detailed fundamental understanding of
      the interplay between the regulation of ammonium production and assimilation is
      of paramount importance in exploiting existing and potentially engineering new
      plant-diazotroph relationships for improved agriculture.

PMID- 28432098
TI  - Inhibitory Effect of Coumarin on Syntrophic Fatty Acid-Oxidizing and Methanogenic
      Cultures and Biogas Reactor Microbiomes.
AB  - Coumarins are widely found in plants as natural constituents having antimicrobial
      activity. When considering plants that are rich in coumarins for biogas
      production, adverse effects on microorganisms driving the anaerobic digestion
      process are expected. Furthermore, coumarin derivatives, like warfarin, which are
      used as anticoagulating medicines, are found in wastewater, affecting its
      treatment. Coumarin, the structure common to all coumarins, inhibits the
      anaerobic digestion process. However, the details of this inhibition are still
      elusive. Here, we studied the impact of coumarin on acetogenesis and
      methanogenesis. First, coumarin was applied at four concentrations between 0.25
      and 1 g . liter-1 to pure cultures of the methanogens Methanosarcina barkeri and
      Methanospirillum hungatei, which resulted in up to 25% less methane production.
      Acetate production of syntrophic propionate- and butyrate-degrading cultures of
      Syntrophobacter fumaroxidans and Syntrophomonas wolfei was inhibited by 72% at a
      coumarin concentration of 1 g . liter-1 Coumarin also inhibited acetogenesis and
      acetoclastic methanogenesis in a complex biogas reactor microbiome. When a
      coumarin-adapted microbiome was used, acetogenesis and methanogenesis were not
      inhibited. According to amplicon sequencing of bacterial 16S rRNA genes and mcrA
      genes, the communities of the two microbiomes were similar, although
      Methanoculleus was more abundant and Methanobacterium less abundant in the
      coumarin-adapted than in the nonadapted microbiome. Our results suggest that well
      dosed feeding with coumarin-rich feedstocks to full-scale biogas reactors while
      keeping the coumarin concentrations below 0.5 g . liter-1 will allow adaptation
      to coumarins by structural and functional community reorganization and coumarin
      degradation.IMPORTANCE Coumarins from natural and anthropogenic sources have an
      inhibitory impact on the anaerobic digestion process. Here, we studied in detail
      the adverse effects of the model compound coumarin on acetogenesis and
      methanogenesis, which are two important steps of the anaerobic digestion process.
      Coumarin concentrations lower than 0.5 g . liter-1 had only a minor impact. Even
      though similar inhibitory effects can be assumed for coumarin derivatives, little
      effects on the anaerobic treatment of wastewater are expected where
      concentrations of coumarin derivatives are lower than 0.5 g . liter-1 However,
      when full-scale reactors are fed with coumarin-rich feedstocks, the biogas
      processes might be inhibited. Hence, these feedstocks should be utilized in a
      well-dosed manner or after adaptation of the microbial community.

PMID- 28432099
TI  - Acute Hepatopancreatic Necrosis Disease-Causing Vibrio parahaemolyticus Strains
      Maintain an Antibacterial Type VI Secretion System with Versatile Effector
      Repertoires.
AB  - Acute hepatopancreatic necrosis disease (AHPND) is a newly emerging shrimp
      disease that has severely damaged the global shrimp industry. AHPND is caused by
      toxic strains of Vibrio parahaemolyticus that have acquired a "selfish plasmid"
      encoding the deadly binary toxins PirAvp/PirBvp To better understand the
      repertoire of virulence factors in AHPND-causing V. parahaemolyticus, we
      conducted a comparative analysis using the genome sequences of the clinical
      strain RIMD2210633 and of environmental non-AHPND and toxic AHPND isolates of V.
      parahaemolyticus Interestingly, we found that all of the AHPND strains, but none
      of the non-AHPND strains, harbor the antibacterial type VI secretion system 1
      (T6SS1), which we previously identified and characterized in the clinical isolate
      RIMD2210633. This finding suggests that the acquisition of this T6SS might confer
      to AHPND-causing V. parahaemolyticus a fitness advantage over competing bacteria
      and facilitate shrimp infection. Additionally, we found highly dynamic effector
      loci in the T6SS1 of AHPND-causing strains, leading to diverse effector
      repertoires. Our discovery provides novel insights into AHPND-causing pathogens
      and reveals a potential target for disease control.IMPORTANCE Acute
      hepatopancreatic necrosis disease (AHPND) is a serious disease that has caused
      severe damage and significant financial losses to the global shrimp industry. To
      better understand and prevent this shrimp disease, it is essential to thoroughly
      characterize its causative agent, Vibrio parahaemolyticus Although the plasmid
      encoded binary toxins PirAvp/PirBvp have been shown to be the primary cause of
      AHPND, it remains unknown whether other virulent factors are commonly present in
      V. parahaemolyticus and might play important roles during shrimp infection. Here,
      we analyzed the genome sequences of clinical, non-AHPND, and AHPND strains to
      characterize their repertoires of key virulence determinants. Our studies reveal
      that an antibacterial type VI secretion system is associated with the AHPND
      strains and differentiates them from non-AHPND strains, similar to what was seen
      with the PirA/PirB toxins. We propose that T6SS1 provides a selective advantage
      during shrimp infections.

PMID- 28432100
TI  - Casein Kinase I Isoform Hrr25 Is a Negative Regulator of Haa1 in the Weak Acid
      Stress Response Pathway in Saccharomyces cerevisiae.
AB  - Haa1 is a transcription factor that adapts Saccharomyces cerevisiae cells to weak
      organic acid stresses by activating the expression of various genes. Many of
      these genes encode membrane proteins, such as TPO2 and YRO2 How Haa1 is activated
      by weak acids is not clear. Here, we show that casein kinase I isoform Hrr25 is
      an important negative regulator of Haa1. Haa1 is known to be multiply
      phosphorylated. We found that mutations in HRR25 lead to reduced Haa1
      phosphorylation and increased expression of Haa1 target genes and that Hrr25
      interacts with Haa1. The other three casein kinase I isoforms, Yck1, Yck2, and
      Yck3, do not seem to play critical roles in Haa1 regulation. Hrr25 has a 200
      residue C-terminal region, including a proline- and glutamine-rich domain. Our
      data suggest that the C-terminal region of Hrr25 is required for normal
      inhibition of expression of Haa1 target genes TPO2 and YRO2 and is important for
      cell growth but is not required for cell morphogenesis. We propose that Hrr25 is
      an important regulator of cellular adaptation to weak acid stress by inhibiting
      Haa1 through phosphorylation.IMPORTANCE Our study has revealed the casein kinase
      I protein Hrr25 to be a negative regulator of Haa1, a transcription factor
      mediating the cellular response to stresses caused by weak acids. Many studies
      have focused on the target genes of Haa1 and their roles in weak acid stress
      responses, but little has been reported on the regulatory mechanism of Haa1. Weak
      acids, such as acetic acid, have long been used for food preservation by slowing
      down the growth of fungal species, including S. cerevisiae In the biofuel
      industry, acetic acid in the lignocellulosic hydrolysates limits the production
      of ethanol, which is undesirable. By understanding how Haa1 is regulated, we can
      make advances in the field of food sciences to better preserve food and engineer
      acetic acid-resistant strains that will increase productivity in the biofuel
      industry.

PMID- 28432101
TI  - Polio and Measles Down the Drain: Environmental Enterovirus Surveillance in the
      Netherlands, 2005 to 2015.
AB  - Polioviruses (PVs) are members of the genus Enterovirus In the Netherlands, the
      exclusion of PV circulation is based on clinical enterovirus (EV) surveillance
      (CEVS) of EV-positive cases and routine environmental EV surveillance (EEVS)
      conducted on sewage samples collected in the region of the Netherlands where
      vaccination coverage is low due to religious reasons. We compared the EEVS data
      to those of the CEVS to gain insight into the relevance of EEVS for poliovirus
      and nonpolio enterovirus surveillance. Following the polio outbreak in Syria,
      EEVS was performed at the primary refugee center in Ter Apel in the Netherlands,
      and data were compared to those of CEVS and EEVS. Furthermore, we assessed the
      feasibility of poliovirus detection by EEVS using measles virus detection in
      sewage during a measles outbreak as a proxy. Two Sabin-like PVs were found in
      routine EEVS, 11 Sabin-like PVs were detected in the CEVS, and one Sabin-like PV
      was found in the Ter Apel sewage. We observed significant differences between the
      three programs regarding which EVs were found. In 6 sewage samples collected
      during the measles outbreak in 2013, measles virus RNA was detected in regions
      where measles cases were identified. In conclusion, we detected PVs, nonpolio
      EVs, and measles virus in sewage and showed that environmental surveillance is
      useful for poliovirus detection in the Netherlands, where live oral poliovirus
      vaccine is not used and communities with lower vaccination coverage exist. EEVS
      led to the detection of EV types not seen in the CEVS, showing that EEVS is
      complementary to CEVS.IMPORTANCE We show that environmental enterovirus
      surveillance complements clinical enterovirus surveillance for poliovirus
      detection, or exclusion, and for nonpolio enterovirus surveillance. Even in the
      presence of adequate surveillance, only a very limited number of Sabin-like
      poliovirus strains were detected in a 10-year period, and no signs of
      transmission of oral polio vaccine (OPV) strains were found in a country using
      exclusively inactivated polio vaccine (IPV). Measles viruses can be detected
      during an outbreak in sewage samples collected and concentrated following
      procedures used for environmental enterovirus surveillance.

PMID- 28432103
TI  - Morphology and cardiac physiology are differentially affected by temperature in
      developing larvae of the marine fish mahi-mahi (Coryphaena hippurus).
AB  - Cardiovascular performance is altered by temperature in larval fishes, but how
      acute versus chronic temperature exposures independently affect cardiac
      morphology and physiology in the growing larva is poorly understood.
      Consequently, we investigated the influence of water temperature on cardiac
      plasticity in developing mahi-mahi. Morphological (e.g. standard length, heart
      angle) and physiological cardiac variables (e.g. heart rate fH, stroke volume,
      cardiac output) were recorded under two conditions by imaging: (i) under acute
      temperature exposure where embryos were reared at 25 degrees C up to 128 h post
      fertilization (hpf) and then acutely exposed to 25 (rearing temperature), 27 and
      30 degrees C; and (ii) at two rearing (chronic) temperatures of 26 and 30 degrees
      C and performed at 32 and 56 hpf. Chronic elevated temperature improved
      developmental time in mahi-mahi. Heart rates were 1.2-1.4-fold higher under
      exposure of elevated acute temperatures across development (Q10>=2.0). Q10 for
      heart rate in acute exposure was 1.8-fold higher compared to chronic exposure at
      56 hpf. At same stage, stroke volume was temperature independent (Q10~1.0).
      However, larvae displayed higher stroke volume later in stage. Cardiac output in
      developing mahi-mahi is mainly dictated by chronotropic rather than inotropic
      modulation, is differentially affected by temperature during development and is
      not linked to metabolic changes.

PMID- 28432104
TI  - Dancing attraction: followers of honey bee tremble and waggle dances exhibit
      similar behaviors.
AB  - The function of the honey bee tremble dance and how it attracts signal receivers
      is poorly understood. We tested the hypothesis that tremble followers and waggle
      followers exhibit the same dance-following behavior. If correct, this could unify
      our understanding of dance following, provide insight into dance information
      transfer, and offer a way to identify the signal receivers of tremble dance
      information. Followers showed similar initial attraction to and tracking of
      dancers. However, waggle dancers were faster than tremble dancers, and follower
      forward, -sideways, and -angular velocities were generally similar to the
      velocities of their respective dancers. Waggle dancers attracted followers from
      1.3-fold greater distances away than tremble dancers. Both follower types were
      attracted to the lateral sides of dancers, but tremble followers were more
      attracted to the dancer's head, and waggle followers were more attracted to the
      dancer's abdomen. Tremble dancers engaged in 4-fold more brief food exchanges
      with their followers than waggle dancers. The behaviors of both follower types
      are therefore relatively conserved. Researchers can now take the next steps,
      observing tremble followers to determine their subsequent behaviors and testing
      the broader question of whether follower attraction and tracking is conserved in
      a wide range of social insects.

PMID- 28432102
TI  - Two Distinct alpha-l-Arabinofuranosidases in Caldicellulosiruptor Species Drive
      Degradation of Arabinose-Based Polysaccharides.
AB  - Species in the extremely thermophilic genus Caldicellulosiruptor can degrade
      unpretreated plant biomass through the action of multimodular glycoside
      hydrolases. To date, most focus with these bacteria has been on hydrolysis of
      glucans and xylans, while the biodegradation mechanism for arabinose-based
      polysaccharides remains unclear. Here, putative alpha-l-arabinofuranosidases
      (AbFs) were identified in Caldicellulosiruptor species by homology to less
      thermophilic versions of these enzymes. From this screen, an extracellular XynF
      was determined to be a key factor in hydrolyzing alpha-1,2-, alpha-1,3-, and
      alpha-1,5-l-arabinofuranosyl residues of arabinose-based polysaccharides.
      Combined with a GH11 xylanase (XynA), XynF increased arabinoxylan hydrolysis more
      than 6-fold compared to the level seen with XynA alone, likely the result of XynF
      removing arabinofuranosyl side chains to generate linear xylans that were readily
      degraded. A second AbF, the intracellular AbF51, preferentially cleaved the alpha
      1,5-l-arabinofuranosyl glycoside bonds within sugar beet arabinan. beta
      Xylosidases, such as GH39 Xyl39B, facilitated the hydrolysis of arabinofuranosyl
      residues at the nonreducing terminus of the arabinose-branched xylo
      oligosaccharides by AbF51. These results demonstrate the separate but
      complementary contributions of extracellular XynF and cytosolic AbF51 in
      processing the bioconversion of arabinose-containing oligosaccharides to
      fermentable monosaccharides.IMPORTANCE Degradation of hemicellulose, due to its
      complex chemical structure, presents a major challenge during bioconversion of
      lignocellulosic biomass to biobased fuels and chemicals. Degradation of arabinose
      containing polysaccharides, in particular, can be a key bottleneck in this
      process. Among Caldicellulosiruptor species, the multimodular arabinofuranosidase
      XynF is present in only selected members of this genus. This enzyme exhibited
      high hydrolysis activity, broad specificity, and strong synergism with other
      hemicellulases acting on arabino-polysaccharides. An intracellular
      arabinofuranosidase, AbF51, occurs in all Caldicellulosiruptor species and, in
      conjunction with xylosidases, processes the bioconversion of arabinose-branched
      oligosaccharides to fermentable monosaccharides. Taken together, the data suggest
      that plant biomass degradation in Caldicellulosiruptor species involves
      extracellular XynF that acts synergistically with other hemicellulases to digest
      arabino-polysaccharides that are subsequently transported and degraded further by
      intracellular AbF51 to produce short-chain arabino sugars.

PMID- 28432106
TI  - Prohibitin-induced obesity leads to anovulation and polycystic ovary in mice.
AB  - Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the most
      common cause of female infertility. However, its etiology and underlying
      mechanisms remain unclear. Here we report that a transgenic obese mouse (Mito-Ob)
      developed by overexpressing prohibitin in adipocytes develops polycystic ovaries.
      Initially, the female Mito-Ob mice were equally fertile to their wild-type
      littermates. The Mito-Ob mice began to gain weight after puberty, became
      significantly obese between 3-6 months of age, and ~25% of them had become
      infertile by 9 months of age. Despite obesity, female Mito-Ob mice maintained
      glucose homeostasis and insulin sensitivity similar to their wild-type
      littermates. Mito-Ob mice showed morphologically distinct polycystic ovaries and
      elevated estradiol, but normal testosterone and insulin levels. Histological
      analysis of the ovaries showed signs of impaired follicular dynamics, such as
      preantral follicular arrest and reduced number, or absence, of corpus luteum. The
      ovaries of the infertile Mito-Ob mice were closely surrounded by periovarian
      adipose tissue, suggesting a potential role in anovulation. Collectively, these
      data suggest that elevated estradiol and obesity per se might lead to anovulation
      and polycystic ovaries independent of hyperinsulinemia and hyperandrogenism. As
      obesity often coexists with other abnormalities known to be involved in the
      development of PCOS such as insulin resistance, compensatory hyperinsulinemia and
      hyperandrogenism, the precise role of these factors in PCOS remains unclear. Mito
      Ob mice provide an opportunity to study the effects of obesity on anovulation and
      ovarian cyst formation independent of the major drivers of obesity-linked PCOS.

PMID- 28432105
TI  - Centrin diversity and basal body patterning across evolution: new insights from
      Paramecium.
AB  - First discovered in unicellular eukaryotes, centrins play crucial roles in basal
      body duplication and anchoring mechanisms. While the evolutionary status of the
      founding members of the family, Centrin2/Vfl2 and Centrin3/cdc31 has long been
      investigated, the evolutionary origin of other members of the family has received
      less attention. Using a phylogeny of ciliate centrins, we identify two other
      centrin families, the ciliary centrins and the centrins present in the
      contractile filaments (ICL centrins). In this paper, we carry on the functional
      analysis of still not well-known centrins, the ICL1e subfamily identified in
      Paramecium, and show their requirement for correct basal body anchoring through
      interactions with Centrin2 and Centrin3. Using Paramecium as well as a eukaryote
      wide sampling of centrins from completely sequenced genomes, we revisited the
      evolutionary story of centrins. Their phylogeny shows that the centrins
      associated with the ciliate contractile filaments are widespread in eukaryotic
      lineages and could be as ancient as Centrin2 and Centrin3.

PMID- 28432107
TI  - Getting to the heart of matters.

PMID- 28432108
TI  - 'Microbes in sport' -The potential role of the gut microbiota in athlete health
      and performance.

PMID- 28432109
TI  - Early response to ranibizumab predictive of functional outcome after
      dexamethasone for unresponsive diabetic macular oedema.
AB  - PURPOSE: To analyse the effects of intravitreal dexamethasone implant in patients
      suffering from diabetic macular oedema (DME) on the basis of their visual and
      functional response to antivascular endothelial growth factor (VEGF) loading
      dose, in order to early shift to corticosteroids in poorly responding patients.
      DESIGN: Retrospective monocentric study. METHODS: Data of patients with diabetes
      shifted to 0.7 mg dexamethasone implant after three injections of ranibizumab
      (RNB) and followed-up to 12 months were reviewed. Main outcome was the evaluation
      of short-term changes after dexamethasone implant injection, stratifying patients
      on the basis of best-corrected visual acuity (BCVA) and central macular thickness
      (CMT) after RNB loading dose. Secondary outcome was to investigate clinical gain
      maintenance at long-term follow-up. RESULTS: Overall, 45 eyes of 45 patients (23
      males, 51.1%), mean age 69.7+/-9 years, were included in the analysis. After 3
      injections of RNB, 30 eyes (66.7%) had a poor visual response (-4.3+/-10.7
      letters), while 15 eyes (33.3%) disclosed good visual outcome (+13.9+/-9.2
      letters). Patients with poor visual response were associated with limited
      morphological improvement (p=0.04). After 1 month from dexamethasone, only poor
      responders showed relevant increase in BCVA (p=0.006) and reduction in CMT
      (p=0.002), in comparison to good visual response patients, featuring only minor
      clinical effects (p=0.3). The same trend was maintained up to 12 months, after a
      mean of 1.9+/-1.1 dexamethasone administrations. CONCLUSION: Visual and
      anatomical responses after RNB loading dose are significant predictors of both
      early term and long-term visual acuity improvement after switching to
      corticosteroids in patients with DME unresponsive to anti-VEGF.

PMID- 28432110
TI  - Anterior but not posterior choroid changed before and during Valsalva manoeuvre
      in healthy Chinese: a UBM and SS-OCT study.
AB  - PURPOSE: To determine if the anterior choroid is involved in ocular change during
      the Valsalva manoeuvre (VM). MATERIALS AND METHODS: Fifty-three healthy
      volunteers aged 18-65 years with normal visual field test results and no history
      of intraocular pressure (IOP) exceeding 21 mm Hg were recruited. Anterior and
      posterior choroidal changes before and during VM were recorded by ultrasound
      microscope and swept-source optical coherence tomography, respectively.
      Parameters of the anterior segment included ciliary body thickness (CBT0),
      thickness of the choroid at a distance of 4 mm from the root of the iris (CT4),
      anterior placement of the ciliary body (APCB) and trabecular-ciliary angle (TCA).
      Thickness of different layers of retina and posterior choroid were also measured
      and compared before and during VM. IOP, blood pressure (BP), heart rate (HR),
      axial length, spherical equivalent refractive error and pupil diameter (PD) were
      also recorded and analysed. RESULTS: VM caused elevated IOP, systolic BP,
      diastolic BP and increased HR. There was a significant increase in anterior
      parameters including CBT0, CT4 and APCB (p<0.001), but not in TCA or PD (p>0.05).
      The mean change of CBT0, CT4 and APCB were: from 1.00+/-0.09 mm to 1.11+/-0.10 mm
      (p<0.001), from 0.29+/-0.04 mm to 0.36+/-0.05 mm (p<0.001), from 0.76+/-0.11 mm
      to 0.88+/-0.13 mm (p<0.001), respectively. However, there is no significant
      change in posterior choroid (from 215.74+/-60.23 um to 214.82+/-61.32 um,
      p=0.17). CONCLUSION: We found that VM did not affect the posterior choroid, but
      it did cause thickening of the anterior choroid and the ciliary body, both of
      which led to a larger anterior placement of the ciliary body and a narrowed
      anterior chamber. The anterior (but not the posterior) choroid could be related
      to IOP elevation and a narrowed anterior chamber in primary angle closure
      diseases.

PMID- 28432111
TI  - Regional vascular density-visual field sensitivity relationship in glaucoma
      according to disease severity.
AB  - AIMS: To study whether there are global and regional relationships between
      peripapillary vascular density (pVD) assessed by optical coherence tomography
      angiography (OCT-A) and visual field (VF) mean sensitivity at different glaucoma
      stages. METHODS: Microvascular images and peripapillary retinal nerve fibre layer
      (pRNFL) thicknesses were obtained using a Cirrus OCT-A device in 91 glaucoma
      subjects. The pVD was measured at various spatial locations according to the
      Garway-Heath map, using a MATLAB software (The MathWorks, Natick, Massachusetts).
      VF mean sensitivity (VFMS) was recorded in the 1/L scale. Global and regional
      vasculature-function (pVD vs VFMS) relationships were assessed in separate
      patient groups at mild and moderate-to-advanced stages of glaucoma. RESULTS: The
      pVDs at superotemporal and inferotemporal regions were significantly associated
      with corresponding VFMS in mild glaucoma (p<0.05). In moderate-to-advanced
      glaucoma, there were significant associations between pVD and VFMS, regardless of
      location. The association between global pVD and VFMS was significantly stronger
      than that between global pRNFL thickness and VFMS in moderate-to-advanced stage
      glaucoma (p <0.05). CONCLUSION: Global and regional pVD measured by OCT-A was
      significantly associated with corresponding VFMS in moderate-to-advanced
      glaucoma. OCT-A may be useful in monitoring glaucoma at various stages.

PMID- 28432112
TI  - Reduction of severe visual loss and complications following intra-arterial
      chemotherapy (IAC) for refractory retinoblastoma.
AB  - BACKGROUND: Intra-arterial chemotherapy (IAC) for retinoblastoma has been
      documented as causing visual loss and ocular motility problems. A lack of safety
      data has precluded its acceptance in all centres. METHODS: Retrospective cohort
      study of patients with retinoblastoma from 2013 to 2015 who had a healthy foveola
      and relapsed following systemic chemotherapy. All required IAC. The correlation
      of complications with doses of melphalan +/- topotecan used and putative
      catheterisation complications was assessed. Ocular complications were determined
      using vision, macular (including pattern visual evoked potentials (PVEPs)),
      retinal electroretinograms (ERGs) and ocular motility functions. Efficacy (tumour
      control) was also assessed. RESULTS: All eyes had age appropriate doses of
      melphalan with five having additional doses of topotecan. Severe physiological
      reactions requiring adrenaline were seen in six patients during the
      catheterisation procedure. Difficulty was documented in accessing the ophthalmic
      artery in 7/27 catheterisations. The median/mean number of courses of
      chemotherapy was three. No child had severe visual loss as assessed by age
      appropriate tests (median follow-up 20.9 months, range 3.7-35.2 months). One
      child had nasal choroidal ischaemia and a sixth nerve palsy. Post-IAC PVEPs were
      performed in eight and reported as normal. All post-IAC ERGs were normal apart
      from one (total dose 20 mg melphalan 0.8 mg topotecan). Tumour control was
      achieved in six of nine cases. CONCLUSION: The proportion of visual and ocular
      motility complications may be reduced by providing age-adjusted doses of
      melphalan. Dose rather than complications from catheterisation is the most
      important risk factor for ocular injury.

PMID- 28432113
TI  - Automated quantitative characterisation of retinal vascular leakage and
      microaneurysms in ultra-widefield fluorescein angiography.
AB  - Ultra-widefield fluorescein angiography (UWFA) is an emerging imaging modality
      used to characterise pathology in the retinal vasculature such as microaneurysms
      (MAs) and vascular leakage. Despite its potential value for diagnosis and disease
      surveillance, objective quantitative assessment of retinal pathology by UWFA is
      currently limited because it requires laborious manual segmentation by trained
      human graders. In this report, we describe a novel fully automated software
      platform, which segments MAs and leakage areas in native and dewarped UWFA images
      with retinal vascular disease. Comparison of the algorithm with human grader
      generated gold standards demonstrated significant strong correlations for MA and
      leakage areas (intraclass correlation coefficient (ICC)=0.78-0.87 and ICC=0.70
      0.86, respectively, p=2.1*10-7 to 3.5*10-10 and p=7.8*10-6 to 1.3*10-9,
      respectively). These results suggest the algorithm performs similarly to human
      graders in MA and leakage segmentation and may be of significant utility in
      clinical and research settings.

PMID- 28432114
TI  - Intereye asymmetry in bilateral keratoconus, keratoconus suspect and normal eyes
      and its relationship with disease severity.
AB  - BACKGROUND/AIM: To describe the intereye asymmetry in patients with keratoconus
      (KC), keratoconus suspect (KCS) and normal participants, and to evaluate the
      relationship between asymmetry and disease severity. METHODS: In this prospective
      observational comparative study, 446 patients with bilateral KC, 68 patients with
      bilateral KCS and 306 normal participants underwent topographic, keratometric and
      pachymetric evaluations by Pentacam as well as refractive and visual acuity
      examinations. The intereye asymmetry in each parameter was calculated and
      compared between the groups. RESULTS: All parameters were significantly different
      between the worse and better eyes in the KC group (p<0.05), but not in the KCS
      and normal groups. No significant differences were observed in the measurements
      of the worse and better eyes of the normal group (p>0.05). There was a
      statistically significant greater intereye asymmetry in all parameters in the KC
      group compared with the KCS and normal groups (p<0.05). The intraclass
      correlations were poor in patients with KC, moderate to good in patients
      suspected with KC and strong in normal participants. There were statistically
      significant relationships between the intereye asymmetry in all parameters and KC
      severity in the worse eye in which intereye asymmetry significantly increased
      with an increase in disease severity, based on Keratoconus Severity Score
      classification (p<0.05). According to receiver operating characteristic analysis,
      the intereye asymmetry would effectively discriminate KC and KCS from normal
      eyes. CONCLUSION: KC is an asymmetric disease, and the degree of asymmetry is
      associated with disease severity. The analysis of intereye asymmetry should be
      performed along with unilateral evaluation in the screening of KC.

PMID- 28432115
TI  - Effects of Exercise on Vascular Function, Structure, and Health in Humans.
AB  - Physical activity has profound impacts on the vasculature in humans. Acute
      exercise induces immediate changes in artery function, whereas repeated episodic
      bouts of exercise induce chronic functional adaptation and, ultimately,
      structural arterial remodeling. The nature of these changes in function and
      structure are dependent on the characteristics of the training load and may be
      modulated by other factors such as exercise-induced inflammation and oxidative
      stress. The clinical implications of these physiological adaptations are
      profound. Exercise impacts on the development of atherosclerosis and on the
      incidence of primary and secondary cardiovascular events, including myocardial
      infarction and stroke. Exercise also plays a role in the amelioration of other
      chronic diseases that possess a vascular etiology, including diabetes and
      dementia. The mechanisms responsible for these effects of exercise on the
      vasculature are both primary and secondary in nature, in that the benefits
      conferred by changes in cardiovascular risk factors such as lipid profiles and
      blood pressure occur in concert with direct effects of arterial shear stress and
      mechanotransduction. From an evolutionary perspective, exercise is an essential
      stimulus for the maintenance of vascular health: exercise is vascular medicine.

PMID- 28432116
TI  - Effects of Exercise and Aging on Skeletal Muscle.
AB  - A substantial loss of muscle mass and strength (sarcopenia), a decreased
      regenerative capacity, and a compromised physical performance are hallmarks of
      aging skeletal muscle. These changes are typically accompanied by impaired muscle
      metabolism, including mitochondrial dysfunction and insulin resistance. A
      challenge in the field of muscle aging is to dissociate the effects of
      chronological aging per se on muscle characteristics from the secondary influence
      of lifestyle and disease processes. Remarkably, physical activity and exercise
      are well-established countermeasures against muscle aging, and have been shown to
      attenuate age-related decreases in muscle mass, strength, and regenerative
      capacity, and slow or prevent impairments in muscle metabolism. We posit that
      exercise and physical activity can influence many of the changes in muscle during
      aging, and thus should be emphasized as part of a lifestyle essential to healthy
      aging.

PMID- 28432118
TI  - Molecular Basis for Exercise-Induced Fatigue: The Importance of Strictly
      Controlled Cellular Ca2+ Handling.
AB  - The contractile function of skeletal muscle declines during intense or prolonged
      physical exercise, that is, fatigue develops. Skeletal muscle fibers fatigue
      acutely during highly intense exercise when they have to rely on anaerobic
      metabolism. Early stages of fatigue involve impaired myofibrillar function,
      whereas decreased Ca2+ release from the sarcoplasmic reticulum (SR) becomes more
      important in later stages. SR Ca2+ release can also become reduced with more
      prolonged, lower intensity exercise, and it is then related to glycogen
      depletion. Increased reactive oxygen/nitrogen species can cause long-lasting
      impairments in SR Ca2+ release resulting in a prolonged force depression after
      exercise. In this article, we discuss molecular and cellular mechanisms of the
      above fatigue-induced changes, with special focus on multiple mechanisms to
      decrease SR Ca2+ release to avoid energy depletion and preserve muscle fiber
      integrity. We also discuss fatigue-related effects of exercise-induced Ca2+
      fluxes over the sarcolemma and between the cytoplasm and mitochondria.

PMID- 28432117
TI  - Control of Muscle Metabolism by the Mediator Complex.
AB  - Exercise represents an energetic challenge to whole-body homeostasis. In skeletal
      muscle, exercise activates a variety of signaling pathways that culminate in the
      nucleus to regulate genes involved in metabolism and contractility; however, much
      remains to be learned about the transcriptional effectors of exercise. Mediator
      is a multiprotein complex that links signal-dependent transcription factors and
      other transcriptional regulators with the basal transcriptional machinery,
      thereby serving as a transcriptional "hub." In this article, we discuss recent
      studies highlighting the role of Mediator subunits in metabolic regulation and
      glucose metabolism, as well as exercise responsiveness. Elucidation of the roles
      of Mediator subunits in metabolic control has revealed new mechanisms and
      molecular targets for the modulation of metabolism and metabolic disorders.

PMID- 28432119
TI  - Temozolomide treatment can improve overall survival in aggressive pituitary
      tumors and pituitary carcinomas.
AB  - OBJECTIVES: Only few retrospective studies have reported an efficacy rate of
      temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long
      term survival of treated patients is rarely evaluated. We therefore aimed to
      describe the use of TMZ on PT in clinical practice and evaluate the long-term
      survival. DESIGN: Multicenter retrospective study by members of the French
      Society of Endocrinology. METHODS: Forty-three patients (14 women) treated with
      TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23)
      or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological
      characteristics of PT, as well as data from treatment evaluation and from the
      last follow-up were recorded. A partial response was considered as a decrease in
      the maximal tumor diameter by more than 30% and/or in the hormonal rate by more
      than 50% at the end of treatment. RESULTS: The median treatment duration was 6.5
      cycles (range 2-24), using a standard regimen for most and combined radiotherapy
      for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor
      at diagnosis was associated with a poor response. The median follow-up after the
      end of treatment was 16 months (0-72). Overall survival was significantly higher
      among responders (P = 0.002); however, ten patients relapsed 5 months (0-57)
      after the end of TMZ treatment, five in whom TMZ was reinitiated without success.
      DISCUSSION: Patients in our series showed a 51.2% response rate to TMZ, with an
      improved survival among responders despite frequent relapses. Our study
      highlights the high variability and lack of standardization of treatment
      protocols.

PMID- 28432120
TI  - Two glycosaminoglycan-binding domains of the mouse cytomegalovirus-encoded
      chemokine MCK-2 are critical for oligomerization of the full-length protein.
AB  - Chemokines are essential for antimicrobial host defenses and tissue repair.
      Herpesviruses and poxviruses also encode chemokines, copied from their hosts and
      repurposed for multiple functions, including immune evasion. The CC chemokine MCK
      2 encoded by mouse CMV (MCMV) has an atypical structure consisting of a classic
      chemokine domain N-terminal to a second unique domain, resulting from the
      splicing of MCMV ORFs m131 and m129 MCK-2 is essential for full MCMV infectivity
      in macrophages and for persistent infection in the salivary gland. However,
      information about its mechanism of action and specific biochemical roles for the
      two domains has been lacking. Here, using genetic, chemical, and enzymatic
      analyses of multiple mouse cell lines as well as primary mouse fibroblasts from
      salivary gland and lung, we demonstrate that MCK-2 binds glycosaminoglycans
      (GAGs) with affinities in the following order: heparin > heparan sulfate >
      chondroitin sulfate = dermatan sulfate. Both MCK-2 domains bound these GAGs
      independently, and computational analysis together with site-directed mutagenesis
      identified five basic residues distributed across the N terminus and the 30s and
      50s loops of the chemokine domain that are important GAG binding determinants.
      Both domains were required for GAG-dependent oligomerization of full-length MCK
      2. Thus, MCK-2 is an atypical viral chemokine consisting of a CC chemokine domain
      and a unique non-chemokine domain, both of which bind GAGs and are critical for
      GAG-dependent oligomerization of the full-length protein.

PMID- 28432121
TI  - The Lon protease-like domain in the bacterial RecA paralog RadA is required for
      DNA binding and repair.
AB  - Homologous recombination (HR) plays an essential role in the maintenance of
      genome integrity. RecA/Rad51 paralogs have been recognized as an important factor
      of HR. Among them, only one bacterial RecA/Rad51 paralog, RadA, is involved in HR
      as an accessory factor of RecA recombinase. RadA has a unique Lon protease-like
      domain (LonC) at its C terminus, in addition to a RecA-like ATPase domain. Unlike
      Lon protease, RadA's LonC domain does not show protease activity but is still
      essential for RadA-mediated DNA repair. Reconciling these two facts has been
      difficult because RadA's tertiary structure and molecular function are unknown.
      Here, we describe the hexameric ring structure of RadA's LonC domain, as
      determined by X-ray crystallography. The structure revealed the two positively
      charged regions unique to the LonC domain of RadA are located at the intersubunit
      cleft and the central hole of a hexameric ring. Surprisingly, a functional domain
      analysis demonstrated the LonC domain of RadA binds DNA, with site-directed
      mutagenesis showing that the two positively charged regions are critical for this
      DNA-binding activity. Interestingly, only the intersubunit cleft was required for
      the DNA-dependent stimulation of ATPase activity of RadA, and at least the
      central hole was essential for DNA repair function. Our data provide the
      structural and functional features of the LonC domain and their function in RadA
      mediated DNA repair.

PMID- 28432123
TI  - An amphipathic alpha-helix directs palmitoylation of the large intracellular loop
      of the sodium/calcium exchanger.
AB  - The electrogenic sodium/calcium exchanger (NCX) mediates bidirectional calcium
      transport controlled by the transmembrane sodium gradient. NCX inactivation
      occurs in the absence of phosphatidylinositol 4,5-bisphosphate and is facilitated
      by palmitoylation of a single cysteine at position 739 within the large
      intracellular loop of NCX. The aim of this investigation was to identify the
      structural determinants of NCX1 palmitoylation. Full-length NCX1 (FL-NCX1) and a
      YFP fusion protein of the NCX1 large intracellular loop (YFP-NCX1) were expressed
      in HEK cells. Single amino acid changes around Cys-739 in FL-NCX1 and deletions
      on the N-terminal side of Cys-739 in YFP-NCX1 did not affect NCX1 palmitoylation,
      with the exception of the rare human polymorphism S738F, which enhanced FL-NCX1
      palmitoylation, and D741A, which modestly reduced it. In contrast, deletion of a
      21-amino acid segment enriched in aromatic amino acids on the C-terminal side of
      Cys-739 abolished YFP-NCX1 palmitoylation. We hypothesized that this segment
      forms an amphipathic alpha-helix whose properties facilitate Cys-739
      palmitoylation. Introduction of negatively charged amino acids to the hydrophobic
      face or of helix-breaking prolines impaired palmitoylation of both YFP-NCX1 and
      FL-NCX1. Alanine mutations on the hydrophilic face of the helix significantly
      reduced FL-NCX1 palmitoylation. Of note, when the helix-containing segment was
      introduced adjacent to cysteines that are not normally palmitoylated, they became
      palmitoylation sites. In conclusion, we have identified an amphipathic alpha
      helix in the NCX1 large intracellular loop that controls NCX1 palmitoylation.
      NCX1 palmitoylation is governed by a distal secondary structure element rather
      than by local primary sequence.

PMID- 28432122
TI  - Dual regulation of Stat1 and Stat3 by the tumor suppressor protein PML
      contributes to interferon alpha-mediated inhibition of angiogenesis.
AB  - IFNs are effective in inhibiting angiogenesis in preclinical models and in
      treating several angioproliferative disorders. However, the detailed mechanisms
      of IFNalpha-mediated anti-angiogenesis are not completely understood. Stat1/2/3
      and PML are IFNalpha downstream effectors and are pivotal regulators of
      angiogenesis. Here, we investigated PML's role in the regulation of Stat1/2/3
      activity. In Pml knock-out (KO) mice, ablation of Pml largely reduces IFNalpha
      angiostatic ability in Matrigel plug assays. This suggested an essential role for
      PML in IFNalpha's anti-angiogenic function. We also demonstrated that PML shared
      a large cohort of regulatory genes with Stat1 and Stat3, indicating an important
      role of PML in regulating Stat1 and Stat3 activity. Using molecular tools and
      primary endothelial cells, we demonstrated that PML positively regulates Stat1
      and Stat2 isgylation, a ubiquitination-like protein modification. Accordingly,
      manipulation of the isgylation system by knocking down USP18 altered IFNalpha-PML
      axis-mediated inhibition of endothelial cell migration and network formation.
      Furthermore, PML promotes turnover of nuclear Stat3, and knockdown of PML
      mitigates the effect of LLL12, a selective Stat3 inhibitor, on IFNalpha-mediated
      anti-angiogenic activity. Taken together, we elucidated an unappreciated
      mechanism in which PML, an IFNalpha-inducible effector, possess potent
      angiostatic activity, doing so in part by forming a positive feedforward loop
      with Stat1/2 and a negative feedback loop with Stat3. The interplay between PML,
      Stat1/Stat2, and Stat3 contributes to IFNalpha-mediated inhibition of
      angiogenesis, and disruption of this network results in aberrant IFNalpha
      signaling and altered angiostatic activity.

PMID- 28432124
TI  - Regulation of neurite morphogenesis by interaction between R7 regulator of G
      protein signaling complexes and G protein subunit Galpha13.
AB  - The R7 regulator of G protein signaling family (R7-RGS) critically regulates
      nervous system development and function. Mice lacking all R7-RGS subtypes exhibit
      diverse neurological phenotypes, and humans bearing mutations in the retinal R7
      RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms
      heterotrimeric complexes with Gbeta5 and R7-RGS-binding protein (R7BP) that
      regulate G protein-coupled receptor signaling by accelerating deactivation of
      Gi/o alpha-subunits, several neurological phenotypes of R7-RGS knock-out mice are
      not readily explained by dysregulated Gi/o signaling. Accordingly, we used tandem
      affinity purification and LC-MS/MS to search for novel proteins that interact
      with R7-RGS heterotrimers in the mouse brain. Among several proteins detected, we
      focused on Galpha13 because it had not been linked to R7-RGS complexes before.
      Split-luciferase complementation assays indicated that Galpha13 in its active or
      inactive state interacts with R7-RGS heterotrimers containing any R7-RGS isoform.
      LARG (leukemia-associated Rho guanine nucleotide exchange factor (GEF)), PDZ
      RhoGEF, and p115RhoGEF augmented interaction between activated Galpha13 and R7
      RGS heterotrimers, indicating that these effector RhoGEFs can engage Galpha13.R7
      RGS complexes. Because Galpha13/R7-RGS interaction required R7BP, we analyzed
      phenotypes of neuronal cell lines expressing RGS7 and Gbeta5 with or without
      R7BP. We found that neurite retraction evoked by Galpha12/13-dependent
      lysophosphatidic acid receptors was augmented in R7BP-expressing cells. R7BP
      expression blunted neurite formation evoked by serum starvation by signaling
      mechanisms involving Galpha12/13 but not Galphai/o These findings provide the
      first evidence that R7-RGS heterotrimers interact with Galpha13 to augment
      signaling pathways that regulate neurite morphogenesis. This mechanism expands
      the diversity of functions whereby R7-RGS complexes regulate critical aspects of
      nervous system development and function.

PMID- 28432128
TI  - Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens? Issues
      of Sovereignty, Federalism, and Points-Testing in the Prokaryotic and Eukaryotic
      Spaces of the Host-Microbial Superorganism.
AB  - In contrast to live attenuated vaccines, which are designed to induce immunity
      through a time-limited bloom in systemic tissues, the microbiota is a persistent
      feature of body surfaces, especially the intestine. The immune responses to the
      microbiota are idiosyncratic depending on the niche intimacy of different taxa
      and generally adapt the host to avoid overgrowth and maintain mutualism rather
      than to eliminate the organisms of that taxon. Both the microbiota and the host
      have so much molecular cross talk controlling each other, that the prokaryotic
      and the eukaryotic spaces of the host-microbial superorganism are federal rather
      than sovereign. This molecular cross talk is vital for the immune system to
      develop its mature form. Nevertheless, the microbiota/host biomass spaces are
      rather well separated: The microbiota also limits colonization and penetration of
      pathogens through intense metabolic competition. Immune responses to those
      members of the microbiota mutually adapted to intimate association at mucosal
      surfaces have attractive potential durability, but for clinical use as persistent
      vehicles they would require personalization and engineered reversibility to
      manage the immune context and complications in individual human subjects.

PMID- 28432127
TI  - Sex Differences in Hospitalizations with Maintenance Hemodialysis.
AB  - Hospitalization is a major source of morbidity among patients with ESRD
      undergoing maintenance hemodialysis and is a significant contributor to health
      care costs. To identify subgroups at the highest risk of hospitalization, we
      analyzed by sex, age, and race, adjusting for demographic and clinical
      characteristics, the hospitalization rates, and 30-day readmissions for 333,756
      hospitalizations among 111,653 patients undergoing maintenance hemodialysis in
      facilities operated by a large dialysis organization in the United States (2007
      2011). The overall hospitalization rate was 1.85 hospitalizations per person-year
      and was much higher among women than among men (2.08 versus 1.68 hospitalizations
      per year for women versus men, P<0.001). Age group-specific hospitalization rates
      were consistently higher for women than for men of the same race, and the
      differences were greatest in younger age groups (for example, women aged 18-34
      years and >=75 years had 54% [95% confidence interval, 42% to 67%] and 14% [95%
      confidence interval, 11% to 18%] higher hospitalization rates, respectively, than
      did men of respective ages). Women also had substantially higher risk for 30-day
      readmission, with the largest differences at younger ages. Women had a
      significantly lower serum albumin level than men, and stratification by serum
      albumin level attenuated sex differences in the age group-specific
      hospitalization and 30-day readmission rates. These findings suggest that women
      undergoing maintenance hemodialysis have substantially higher risks for
      hospitalization and 30-day readmission than men. In this cohort, the sex
      differences were greatest in the younger age groups and were attenuated by
      accounting for differences in health status reflected by serum albumin level.

PMID- 28432129
TI  - Do Memory CD4 T Cells Keep Their Cell-Type Programming: Plasticity versus Fate
      Commitment? Complexities of Interpretation due to the Heterogeneity of Memory CD4
      T Cells, Including T Follicular Helper Cells.
AB  - Plasticity is the ability of a cell type to convert to another cell type. There
      are multiple effector CD4 T-cell subtypes, including TH1, TH2, TH17, TH1*, CD4
      CTL, TH9, and TFH cells. It is commonly thought that a CD4 T cell can readily
      show full plasticity-full conversion from one differentiated cell-and this
      propensity to plasticity is possessed by memory CD4 T cells. However, there
      remains no direct demonstration of in vivo-generated resting memory CD4 T-cell
      conversion to a different subtype on secondary antigen challenge in vivo in an
      intact animal at the single-cell level. What has been clearly shown is that CD4 T
      cells possess extraordinary capacity for phenotypic heterogeneity, but that is a
      distinct property from plasticity. Heterogeneity is diversity of the resting
      memory CD4 T-cell population, not conversion of a single differentiated cell into
      another subtype. Apparently, plasticity at the population level can be
      accomplished by either mechanism, as heterogeneity of CD4 T-cell subpopulations
      could affect large shifts in subtype distribution at the overall population level
      via differential exponential expansion and death.

PMID- 28432125
TI  - Sequential adaptive changes in a c-Myc-driven model of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a common cancer that frequently overexpresses
      the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied
      the metabolic, biochemical, and molecular changes accompanying HCC progression,
      regression, and recurrence. These involved altered rates of pyruvate and fatty
      acid beta-oxidation and the likely re-directing of glutamine into biosynthetic
      rather than energy-generating pathways. Initial tumors also showed reduced
      mitochondrial mass and differential contributions of electron transport chain
      complexes I and II to respiration. The uncoupling of complex II's electron
      transport function from its succinate dehydrogenase activity also suggested a
      mechanism by which Myc generates reactive oxygen species. RNA sequence studies
      revealed an orderly progression of transcriptional changes involving pathways
      pertinent to DNA damage repair, cell cycle progression, insulin-like growth
      factor signaling, innate immunity, and further metabolic re-programming. Only a
      subset of functions deregulated in initial tumors was similarly deregulated in
      recurrent tumors thereby indicating that the latter can "normalize" some
      behaviors to suit their needs. An interactive and freely available software tool
      was developed to allow continued analyses of these and other transcriptional
      profiles. Collectively, these studies define the metabolic, biochemical, and
      molecular events accompanyingHCCevolution, regression, and recurrence in the
      absence of any potentially confounding therapies.

PMID- 28432130
TI  - Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens?
      Engaging Our Endogenous Adjuvants.
AB  - The reliance of the immune system on constitutive microbial stimulation support
      the idea that both responsiveness to vaccines and vaccine design need to be
      considered in the context of host-microbiota interactions. Manipulation of
      microbe function or composition via diet alteration or microbiota engraftment may
      soon become a viable approach to control immunity and, as such, vaccine
      responses. Learning from our endogenous original adjuvants could be critical in
      overcoming the enormous hurdle of vaccine design against the numerous pathogens
      that cause chronic infection. Going forward, rationally designed vaccines that
      take advantage of the inherent adjuvant properties of the microbiota could have a
      major impact on the prevention of disease.

PMID- 28432131
TI  - Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens? If So,
      Is There Potential for Efficacious Microbiota-Based Vaccines?
AB  - The gut-resident constituents of the microbiota protect the mucosa from invasive
      pathogens through engagement of both innate and adaptive branches of the immune
      system. They are also likely to provide systemic protection from pathogens, by
      enhancing host robustness and tolerance to the invasive microbes and by inducing
      immune responses that prevent their growth. These properties of commensal
      microbiota, particularly the capacity of some bacteria to induce diverse types of
      antigen-specific immune responses, raises the prospect that they could be
      deployed as vaccine vectors to generate effective local and systemic immunity to
      viral and bacterial pathogens.

PMID- 28432132
TI  - Do Memory CD4 T Cells Keep Their Cell-Type Programming: Plasticity versus Fate
      Commitment? Epigenome: A Dynamic Vehicle for Transmitting and Recording Cytokine
      Signaling.
AB  - CD4+ T cells are critical for the elimination of an immense array of microbial
      pathogens. Although there are aspects of helper T-cell differentiation that can
      be modeled as a classic cell-fate commitment, CD4+ T cells also maintain
      considerable flexibility in their transcriptional program. Here, we present an
      overview of chromatin biology during cellular reprogramming and, within this
      context, envision how the scope of cellular reprogramming may be expanded to
      further our understanding of the controversy surrounding CD4+ T lymphocyte
      plasticity or determinism.

PMID- 28432133
TI  - Do Memory CD4 T Cells Keep Their Cell-Type Programming: Plasticity versus Fate
      Commitment? T-Cell Heterogeneity, Plasticity, and Selection in Humans.
AB  - The wide range of effector and memory T cells is instrumental for immune
      regulation and tailored mechanisms of protection against pathogens. Here, we will
      focus on human CD4 T cells and discuss T-cell plasticity and intraclonal
      diversification in the context of a progressive and selective model of CD4 T-cell
      differentiation.

PMID- 28432134
TI  - TGF-beta1 Signaling and Tissue Fibrosis.
AB  - Activation of TGF-beta1 initiates a program of temporary collagen accumulation
      important to wound repair in many organs. However, the outcome of temporary
      extracellular matrix strengthening all too frequently morphs into progressive
      fibrosis, contributing to morbidity and mortality worldwide. To avoid this
      maladaptive outcome, TGF-beta1 signaling is regulated at numerous levels and
      intimately connected to feedback signals that limit accumulation. Here, we
      examine the current understanding of the core functions of TGF-beta1 in promoting
      collagen accumulation, parallel pathways that promote physiological repair, and
      pathological triggers that tip the balance toward progressive fibrosis. Implicit
      in better understanding of these processes is the identification of therapeutic
      opportunities that will need to be further advanced to limit or reverse organ
      fibrosis.

PMID- 28432135
TI  - Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals.
AB  - Sleep is homeostatically regulated with sleep pressure accumulating with the
      increasing duration of prior wakefulness. Yet, a clear understanding of the
      molecular components of the homeostat, as well as the molecular and cellular
      processes they sense and control to regulate sleep intensity and duration, remain
      a mystery. Here, we will discuss the cellular and molecular basis of sleep
      homeostasis, first focusing on the best homeostatic sleep marker in vertebrates,
      slow wave activity; second, moving to the molecular genetic analysis of sleep
      homeostasis in the fruit fly Drosophila; and, finally, discussing more systemic
      aspects of sleep homeostasis.

PMID- 28432136
TI  - Selective Modulation of the Pupil Light Reflex by Microstimulation of Prefrontal
      Cortex.
AB  - The prefrontal cortex (PFC) is thought to flexibly regulate sensorimotor
      responses, perhaps through modulating activity in other circuits. However, the
      scope of that control remains unknown: it remains unclear whether the PFC can
      modulate basic reflexes. One canonical example of a central reflex is the pupil
      light reflex (PLR): the automatic constriction of the pupil in response to
      luminance increments. Unlike pupil size, which depends on the interaction of
      multiple physiological and neuromodulatory influences, the PLR reflects the
      action of a simple brainstem circuit. However, emerging behavioral evidence
      suggests that the PLR may be modulated by cognitive processes. Although the
      neural basis of these modulations remains unknown, one possible source is the
      PFC, particularly the frontal eye field (FEF), an area of the PFC implicated in
      the control of attention. We show that microstimulation of the rhesus macaque FEF
      alters the magnitude of the PLR in a spatially specific manner. FEF
      microstimulation enhanced the PLR to probes presented within the stimulated
      visual field, but suppressed the PLR to probes at nonoverlapping locations. The
      spatial specificity of this effect parallels the effect of FEF stimulation on
      attention and suggests that FEF is capable of modulating visuomotor
      transformations performed at a lower level than was previously known. These
      results provide evidence of the selective regulation of a basic brainstem reflex
      by the PFC.SIGNIFICANCE STATEMENT The pupil light reflex (PLR) is our brain's
      first and most fundamental mechanism for light adaptation. Although it is often
      described in textbooks as being an immutable reflex, converging evidence suggests
      that the magnitude of the PLR is modulated by cognitive factors. The neural bases
      of these modulations are unknown. Here, we report that microstimulation in the
      prefrontal cortex (PFC) modulates the gain of the PLR, changing how a simple
      reflex circuit responds to physically identical stimuli. These results suggest
      that control structures such as the PFC can add complexity and flexibility to
      even a basic brainstem circuit.

PMID- 28432137
TI  - Dissociation of Choice Formation and Choice-Correlated Activity in Macaque Visual
      Cortex.
AB  - Responses of individual task-relevant sensory neurons can predict monkeys' trial
      by-trial choices in perceptual decision-making tasks. Choice-correlated activity
      has been interpreted as evidence that the responses of these neurons are causally
      linked to perceptual judgments. To further test this hypothesis, we studied
      responses of orientation-selective neurons in V1 and V2 while two macaque monkeys
      performed a fine orientation discrimination task. Although both animals exhibited
      a high level of neuronal and behavioral sensitivity, only one exhibited choice
      correlated activity. Surprisingly, this correlation was negative: when a neuron
      fired more vigorously, the animal was less likely to choose the orientation
      preferred by that neuron. Moreover, choice-correlated activity emerged late in
      the trial, earlier in V2 than in V1, and was correlated with anticipatory
      signals. Together, these results suggest that choice-correlated activity in task
      relevant sensory neurons can reflect postdecision modulatory signals.SIGNIFICANCE
      STATEMENT When observers perform a difficult sensory discrimination, repeated
      presentations of the same stimulus can elicit different perceptual judgments.
      This behavioral variability often correlates with variability in the activity of
      sensory neurons driven by the stimulus. Traditionally, this correlation has been
      interpreted as suggesting a causal link between the activity of sensory neurons
      and perceptual judgments. More recently, it has been argued that the correlation
      instead may originate in recurrent input from other brain areas involved in the
      interpretation of sensory signals. Here, we call both hypotheses into question.
      We show that choice-related activity in sensory neurons can be highly variable
      across observers and can reflect modulatory processes that are dissociated from
      perceptual decision-making.

PMID- 28432138
TI  - Inhibition of Drp1 Ameliorates Synaptic Depression, Abeta Deposition, and
      Cognitive Impairment in an Alzheimer's Disease Model.
AB  - Excessive mitochondrial fission is a prominent early event and contributes to
      mitochondrial dysfunction, synaptic failure, and neuronal cell death in the
      progression of Alzheimer's disease (AD). However, it remains to be determined
      whether inhibition of excessive mitochondrial fission is beneficial in mammal
      models of AD. To determine whether dynamin-related protein 1 (Drp1), a key
      regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic
      target for AD, we examined the effects of Drp1 inhibitor on mitochondrial and
      synaptic dysfunctions induced by oligomeric amyloid-beta (Abeta) in neurons and
      neuropathology and cognitive functions in Abeta precursor protein/presenilin 1
      double-transgenic AD mice. Inhibition of Drp1 alleviates mitochondrial
      fragmentation, loss of mitochondrial membrane potential, reactive oxygen species
      production, ATP reduction, and synaptic depression in Abeta-treated neurons.
      Furthermore, Drp1 inhibition significantly improves learning and memory and
      prevents mitochondrial fragmentation, lipid peroxidation, BACE1 expression, and
      Abeta deposition in the brain in the AD model. These results provide evidence
      that Drp1 plays an important role in Abeta-mediated and AD-related neuropathology
      and in cognitive decline in an AD animal model. Therefore, inhibiting excessive
      Drp1-mediated mitochondrial fission may be an efficient therapeutic avenue for
      AD.SIGNIFICANCE STATEMENT Mitochondrial fission relies on the evolutionary
      conserved dynamin-related protein 1 (Drp1). Drp1 activity and mitochondria
      fragmentation are significantly elevated in the brains of sporadic Alzheimer's
      disease (AD) cases. In the present study, we first demonstrated that the
      inhibition of Drp1 restored amyloid-beta (Abeta)-mediated mitochondrial
      dysfunctions and synaptic depression in neurons and significantly reduced lipid
      peroxidation, BACE1 expression, and Abeta deposition in the brain of AD mice. As
      a result, memory deficits in AD mice were rescued by Drp1 inhibition. These
      results suggest that neuropathology and combined cognitive decline can be
      attributed to hyperactivation of Drp1 in the pathogenesis of AD. Therefore,
      inhibitors of excessive mitochondrial fission, such as Drp1 inhibitors, may be a
      new strategy for AD.

PMID- 28432139
TI  - Feature-Selective Attention Adaptively Shifts Noise Correlations in Primary
      Auditory Cortex.
AB  - Sensory environments often contain an overwhelming amount of information, with
      both relevant and irrelevant information competing for neural resources. Feature
      attention mediates this competition by selecting the sensory features needed to
      form a coherent percept. How attention affects the activity of populations of
      neurons to support this process is poorly understood because population coding is
      typically studied through simulations in which one sensory feature is encoded
      without competition. Therefore, to study the effects of feature attention on
      population-based neural coding, investigations must be extended to include
      stimuli with both relevant and irrelevant features. We measured noise
      correlations (rnoise) within small neural populations in primary auditory cortex
      while rhesus macaques performed a novel feature-selective attention task. We
      found that the effect of feature-selective attention on rnoise depended not only
      on the population tuning to the attended feature, but also on the tuning to the
      distractor feature. To attempt to explain how these observed effects might
      support enhanced perceptual performance, we propose an extension of a simple and
      influential model in which shifts in rnoise can simultaneously enhance the
      representation of the attended feature while suppressing the distractor. These
      findings present a novel mechanism by which attention modulates neural
      populations to support sensory processing in cluttered environments.SIGNIFICANCE
      STATEMENT Although feature-selective attention constitutes one of the building
      blocks of listening in natural environments, its neural bases remain obscure. To
      address this, we developed a novel auditory feature-selective attention task and
      measured noise correlations (rnoise) in rhesus macaque A1 during task
      performance. Unlike previous studies showing that the effect of attention on
      rnoise depends on population tuning to the attended feature, we show that the
      effect of attention depends on the tuning to the distractor feature as well. We
      suggest that these effects represent an efficient process by which sensory cortex
      simultaneously enhances relevant information and suppresses irrelevant
      information.

PMID- 28432140
TI  - Visually Evoked 3-5 Hz Membrane Potential Oscillations Reduce the Responsiveness
      of Visual Cortex Neurons in Awake Behaving Mice.
AB  - Low-frequency membrane potential (Vm) oscillations were once thought to only
      occur in sleeping and anesthetized states. Recently, low-frequency Vm
      oscillations have been described in inactive awake animals, but it is unclear
      whether they shape sensory processing in neurons and whether they occur during
      active awake behavioral states. To answer these questions, we performed two
      photon guided whole-cell Vm recordings from primary visual cortex layer 2/3
      excitatory and inhibitory neurons in awake mice during passive visual stimulation
      and performance of visual and auditory discrimination tasks. We recorded
      stereotyped 3-5 Hz Vm oscillations where the Vm baseline hyperpolarized as the Vm
      underwent high amplitude rhythmic fluctuations lasting 1-2 s in duration. When 3
      5 Hz Vm oscillations coincided with visual cues, excitatory neuron responses to
      preferred cues were significantly reduced. Despite this disruption to sensory
      processing, visual cues were critical for evoking 3-5 Hz Vm oscillations when
      animals performed discrimination tasks and passively viewed drifting grating
      stimuli. Using pupillometry and animal locomotive speed as indicators of arousal,
      we found that 3-5 Hz oscillations were not restricted to unaroused states and
      that they occurred equally in aroused and unaroused states. Therefore, low
      frequency Vm oscillations play a role in shaping sensory processing in visual
      cortical neurons, even during active wakefulness and decision making.SIGNIFICANCE
      STATEMENT A neuron's membrane potential (Vm) strongly shapes how information is
      processed in sensory cortices of awake animals. Yet, very little is known about
      how low-frequency Vm oscillations influence sensory processing and whether they
      occur in aroused awake animals. By performing two-photon guided whole-cell
      recordings from layer 2/3 excitatory and inhibitory neurons in the visual cortex
      of awake behaving animals, we found visually evoked stereotyped 3-5 Hz Vm
      oscillations that disrupt excitatory responsiveness to visual stimuli. Moreover,
      these oscillations occurred when animals were in high and low arousal states as
      measured by animal speed and pupillometry. These findings show, for the first
      time, that low-frequency Vm oscillations can significantly modulate sensory
      signal processing, even in awake active animals.

PMID- 28432141
TI  - The Spacing Effect for Structural Synaptic Plasticity Provides Specificity and
      Precision in Plastic Changes.
AB  - In contrast to trials of training without intervals (massed training), training
      trials spaced over time (spaced training) induce a more persistent memory
      identified as long-term memory (LTM). This phenomenon, known as the spacing
      effect for memory, is poorly understood. LTM is supported by structural synaptic
      plasticity; however, how synapses integrate spaced stimuli remains elusive. Here,
      we analyzed events of structural synaptic plasticity at the single-synapse level
      after distinct patterns of stimulation in motoneurons of Drosophila We found that
      the spacing effect is a phenomenon detected at synaptic level, which determines
      the specificity and the precision in structural synaptic plasticity. Whereas a
      single pulse of stimulation (massed) induced structural synaptic plasticity, the
      same amount of stimulation divided in three spaced stimuli completely prevented
      it. This inhibitory effect was determined by the length of the interstimulus
      intervals. The inhibitory effect of the spacing was lost by suppressing the
      activity of Ras or mitogen-activated protein kinase, whereas the overexpression
      of Ras-WT enhanced it. Moreover, dividing the same total time of stimulation into
      five or more stimuli produced a higher precision in the number of events of
      plasticity. Ras mutations associated with intellectual disability abolished the
      spacing effect and led neurons to decode distinct stimulation patterns as massed
      stimulation. This evidence suggests that the spacing effect for memory may result
      from the effect of the spacing in synaptic plasticity, which appears to be a
      property not limited to neurons involved in learning and memory. We propose a
      model of spacing-dependent structural synaptic plasticity.SIGNIFICANCE STATEMENT
      Long-term memory (LTM) induced by repeated trials spaced over time is known as
      the spacing effect, a common property in the animal kingdom. Altered mechanisms
      in the spacing effect have been found in animal models of disorders with
      intellectual disability, such as Noonan syndrome. Although LTM is sustained by
      structural synaptic plasticity, how synapses integrate spaced stimuli and decode
      them into specific plastic changes remains elusive. Here, we show that the
      spacing effect is a phenomenon detected at the synaptic level, which determines
      the properties of the response in structural plasticity, including precision of
      such response. Whereas suppressing or enhancing Ras/mitogen-activated protein
      kinase signaling changed how synapses decode a pattern of stimuli, a disease
      related Ras allele abolished the spacing effect for plastic changes.

PMID- 28432142
TI  - Structural Similarities between Neuregulin 1-3 Isoforms Determine Their
      Subcellular Distribution and Signaling Mode in Central Neurons.
AB  - The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants
      originating from the use of different genes, alternative promoters, and splice
      variants. NRGs have generally been thought to be transported to axons and
      presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or
      juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2
      accumulates on cell bodies and proximal dendrites, and that NMDAR activity is
      required for shedding of its ectodomain by metalloproteinases. Here we
      systematically investigated the subcellular distribution and processing of major
      NRG isoforms in rat hippocampal neurons. We show that NRG1 isotypes I and II,
      which like NRG2 are single-pass transmembrane proteins with an Ig-like domain,
      share the same subcellular distribution and ectodomain shedding properties. We
      furthermore show that NRG3, like CRD-NRG1, is a dual-pass transmembrane protein
      that harbors a second transmembrane domain near its amino terminus. Both NRG3 and
      CRD-NRG1 cluster on axons through juxtacrine interactions with ErbB4 present on
      GABAergic interneurons. Interestingly, although single-pass NRGs accumulate as
      unprocessed proforms, axonal puncta of CRD-NRG1 and NRG3 are comprised of
      processed protein. Mutations of CRD-NRG1 and NRG3 that render them resistant to
      BACE cleavage, as well as BACE inhibition, result in the loss of axonal puncta
      and in the accumulation of unprocessed proforms in neuronal soma. Together, these
      results define two groups of NRGs with distinct membrane topologies and
      fundamentally different targeting and processing properties in central neurons.
      The implications of this functional diversity for the regulation of neuronal
      processes by the NRG/ErbB pathway are discussed.SIGNIFICANCE STATEMENT Numerous
      Neuregulins (NRGs) are generated through the use of different genes, promoters,
      and alternative splicing, but the functional significance of this evolutionary
      conserved diversity remains poorly understood. Here we show that NRGs can be
      categorized by their membrane topologies. Single-pass NRGs, such as NRG1 Types
      I/II and NRG2, accumulate as unprocessed proforms on cell bodies, and their
      ectodomains are shed by metalloproteinases in response to NMDA receptor
      activation. By contrast, dual-pass CRD-NRG1 and NRG3 are constitutively processed
      by BACE and accumulate on axons where they interact with ErbB4 in juxtacrine
      mode. These findings reveal a previously unknown functional relationship between
      membrane topology, protein processing, and subcellular distribution, and suggest
      that single- and dual-pass NRGs regulate neuronal functions in fundamentally
      different ways.

PMID- 28432143
TI  - Focal Local Field Potential Signature of the Single-Axon Monosynaptic
      Thalamocortical Connection.
AB  - A resurgence has taken place in recent years in the use of the extracellularly
      recorded local field potential (LFP) to investigate neural network activity. To
      probe monosynaptic thalamic activation of cortical postsynaptic target cells, so
      called spike-trigger-averaged LFP (stLFP) signatures have been measured. In these
      experiments, the cortical LFP is measured by multielectrodes covering several
      cortical lamina and averaged on spontaneous spikes of thalamocortical (TC) cells.
      Using a well established forward-modeling scheme, we investigated the biophysical
      origin of this stLFP signature with simultaneous synaptic activation of cortical
      layer-4 neurons, mimicking the effect of a single afferent spike from a single TC
      neuron. Constrained by previously measured intracellular responses of the main
      postsynaptic target cell types and with biologically plausible assumptions
      regarding the spatial distribution of thalamic synaptic inputs into layer 4, the
      model predicted characteristic contributions to monosynaptic stLFP signatures
      both for the regular-spiking (RS) excitatory neurons and the fast-spiking (FS)
      inhibitory interneurons. In particular, the FS cells generated stLFP signatures
      of shorter temporal duration than the RS cells. Added together, a sum of the
      stLFP signatures of these two principal synaptic targets of TC cells were
      observed to resemble experimentally measured stLFP signatures. Outside the volume
      targeted by TC afferents, the resulting postsynaptic LFP signals were found to be
      sharply attenuated. This implies that such stLFP signatures provide a very local
      measure of TC synaptic activation, and that newly developed inverse current
      source density (CSD)-estimation methods are needed for precise assessment of the
      underlying spatiotemporal CSD profiles.SIGNIFICANCE STATEMENT Despite its long
      history and prevalent use, the proper interpretation of the extracellularly
      recorded local field potential (LFP) is still not fully established. Here we
      investigate by biophysical modeling the origin of the focal LFP signature of the
      single-axon monosynaptic thalamocortical connection as measured by spike-trigger
      averaging of cortical LFPs on spontaneous spikes of thalamocortical neurons. We
      find that this LFP signature is well accounted for by a model assuming thalamic
      projections to two cortical layer-4 cell populations: one excitatory (putatively
      regular-spiking cells) and one inhibitory (putatively fast-spiking cells). The
      LFP signature is observed to decay sharply outside the cortical region receiving
      the thalamocortical projection, implying that it indeed provides a very local
      measure of thalamocortical synaptic activation.

PMID- 28432144
TI  - Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and
      Cortical Thickness from Childhood to Young Adulthood.
AB  - Developmental structural neuroimaging studies in humans have long described
      decreases in gray matter volume (GMV) and cortical thickness (CT) during
      adolescence. Gray matter density (GMD), a measure often assumed to be highly
      related to volume, has not been systematically investigated in development. We
      used T1 imaging data collected on the Philadelphia Neurodevelopmental Cohort to
      study age-related effects and sex differences in four regional gray matter
      measures in 1189 youths ranging in age from 8 to 23 years. Custom T1 segmentation
      and a novel high-resolution gray matter parcellation were used to extract GMD,
      GMV, gray matter mass (GMM; defined as GMD * GMV), and CT from 1625 brain
      regions. Nonlinear models revealed that each modality exhibits unique age-related
      effects and sex differences. While GMV and CT generally decrease with age, GMD
      increases and shows the strongest age-related effects, while GMM shows a slight
      decline overall. Females have lower GMV but higher GMD than males throughout the
      brain. Our findings suggest that GMD is a prime phenotype for the assessment of
      brain development and likely cognition and that periadolescent gray matter loss
      may be less pronounced than previously thought. This work highlights the need for
      combined quantitative histological MRI studies.SIGNIFICANCE STATEMENT This study
      demonstrates that different MRI-derived gray matter measures show distinct age
      and sex effects and should not be considered equivalent but complementary. It is
      shown for the first time that gray matter density increases from childhood to
      young adulthood, in contrast with gray matter volume and cortical thickness, and
      that females, who are known to have lower gray matter volume than males, have
      higher density throughout the brain. A custom preprocessing pipeline and a novel
      high-resolution parcellation were created to analyze brain scans of 1189 youths
      collected as part of the Philadelphia Neurodevelopmental Cohort. A clear
      understanding of normal structural brain development is essential for the
      examination of brain-behavior relationships, the study of brain disease, and,
      ultimately, clinical applications of neuroimaging.

PMID- 28432146
TI  - C1q-Dependent Dendritic Cell Cross-Presentation of In Vivo-Formed Antigen
      Antibody Complexes.
AB  - Dendritic cells (DCs) are specialized in Ag engulfment via a wide variety of
      uptake receptors on their cell surface. In the present study we investigated Ag
      uptake and presentation of in vivo-formed Ag-Ab complexes by i.v. injecting mice
      with Ag-specific Abs followed by the cognate Ag. We show by this natural Ab
      mediated Ag targeting system that uptake by splenic APC subsets is severely
      hampered in mice lacking complement factor C1q (C1qa-/-). Moreover, no detectable
      Ag cross-presentation by CD8alpha+ DCs from C1qa-/- mice was found. On the
      contrary, Ag uptake was not hampered by APCs in FcgammaRI/II/III/IV-deficient
      (FcgammaR quadruple-/-) mice, and the cross-presentation ability of CD8alpha+ DCs
      was not affected. In conclusion, we show that C1q rather than FcgammaRs controls
      the Ab-mediated Ag uptake and its presentation by spleen APC subsets to T cells.

PMID- 28432145
TI  - Bacterial Siderophores Hijack Neutrophil Functions.
AB  - Neutrophils are the primary immune cells that respond to inflammation and combat
      microbial transgression. To thrive, the bacteria residing in their mammalian host
      have to withstand the antibactericidal responses of neutrophils. We report that
      enterobactin (Ent), a catecholate siderophore expressed by Escherichia coli,
      inhibited PMA-induced generation of reactive oxygen species (ROS) and neutrophil
      extracellular traps (NETs) in mouse and human neutrophils. Ent also impaired the
      degranulation of primary granules and inhibited phagocytosis and bactericidal
      activity of neutrophils, without affecting their migration and chemotaxis.
      Molecular analysis revealed that Ent can chelate intracellular labile iron that
      is required for neutrophil oxidative responses. Other siderophores (pyoverdine,
      ferrichrome, deferoxamine) likewise inhibited ROS and NETs in neutrophils, thus
      indicating that the chelation of iron may largely explain their inhibitory
      effects. To counter iron theft by Ent, neutrophils rely on the siderophore
      binding protein lipocalin 2 (Lcn2) in a "tug-of-war" for iron. The inhibition of
      neutrophil ROS and NETs by Ent was augmented in Lcn2-deficient neutrophils
      compared with wild-type neutrophils but was rescued by the exogenous addition of
      recombinant Lcn2. Taken together, our findings illustrate the novel concept that
      microbial siderophore's iron-scavenging property may serve as an antiradical
      defense system that neutralizes the immune functions of neutrophils.

PMID- 28432147
TI  - Cutting Edge: A Dual TLR2 and TLR7 Ligand Induces Highly Potent Humoral and Cell
      Mediated Immune Responses.
AB  - TLR agonists are currently being developed and tested as adjuvants in various
      formulations to optimize the immunogenicity and efficacy of vaccines. The aim of
      this study was to evaluate the immunostimulatory properties of a novel compound
      incorporating covalently linked moieties designed to stimulate both TLR2 and
      TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and
      primed substantial populations of cytolytic and highly polyfunctional effector
      CD8+ T cells in vitro, and safely potentiated the immunogenic properties of a
      nanoparticulate Ag in vivo, eliciting humoral responses with a balanced TH1/TH2
      profile in mice. Collectively, these data reveal the potential utility of
      chimeric adjuvants with synergistic activities mediated via TLRs.

PMID- 28432149
TI  - CD73 on T Cells Orchestrates Cardiac Wound Healing After Myocardial Infarction by
      Purinergic Metabolic Reprogramming.
AB  - BACKGROUND: T cells are required for proper healing after myocardial infarction.
      The mechanism of their beneficial action, however, is unknown. The
      proinflammatory danger signal ATP, released from damaged cells, is degraded by
      the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine.
      Here, we investigate the contribution of CD73-derived adenosine produced by T
      cells to cardiac remodeling after ischemia/reperfusion and define its mechanism
      of action. METHODS: Myocardial ischemia (50 minutes followed by reperfusion) was
      induced in global CD73-/- and CD4-CD73-/- mice. Tissue injury, T-cell purinergic
      signaling, cytokines, and cardiac function (magnetic resonance tomography at 9.4
      T over 4 weeks) were analyzed. RESULTS: Changes in functional parameters of CD4
      CD73-/- mice were identical to those in global CD73 knockouts (KOs). T cells
      infiltrating the injured heart significantly upregulated at the gene
      (quantitative polymerase chain reaction) and protein (enzymatic activity) levels
      critical transporters and enzymes (connexin43, connexin37, pannexin-1,
      equilibrative nucleoside transporter 1, CD39, CD73, ecto-nucleotide
      pyrophosphatase/phosphodiesterases 1 and 3, CD157, CD38) for the accelerated
      release and hydrolysis of ATP, cAMP, AMP, and NAD to adenosine. It is surprising
      that a lack of CD39 on T cells (from CD39-/- mice) did not alter ATP hydrolysis
      and very likely involves pyrophosphatases (ecto-nucleotide
      pyrophosphatase/phosphodiesterases 1 and 3). Circulating T cells predominantly
      expressed A2a receptor (A2aR) transcripts. After myocardial infarction, A2b
      receptor (A2bR) transcription was induced in both T cells and myeloid cells in
      the heart. Thus, A2aR and A2bR signaling may contribute to myocardial responses
      after myocardial infarction. In the case of T cells, this was associated with an
      accelerated secretion of proinflammatory and profibrotic cytokines (interleukin
      2, interferon-gamma, and interleukin-17) when CD73 was lacking. Cytokine
      production by T cells from peripheral lymph nodes was inhibited by A2aR
      activation (CGS-21680). The A2bR agonist BAY 60-6583 showed off-target effects.
      The adenosine receptor agonist NECA inhibited interferon-gamma and stimulated
      interleukin-6 production, each of which was antagonized by a specific A2bR
      antagonist (PSB-603). CONCLUSIONS: This work demonstrates that CD73 on T cells
      plays a crucial role in the cardiac wound healing process after myocardial
      infarction. The underlying mechanism involves a profound increase in the
      hydrolysis of ATP/NAD and AMP, resulting primarily from the upregulation of
      pyrophosphatases and CD73. We also define A2bR/A2aR-mediated autacoid feedback
      inhibition of proinflammatory/profibrotic cytokines by T cell-derived CD73.

PMID- 28432150
TI  - Specialist-generalist model of body temperature regulation can be applied at the
      intraspecific level.
AB  - According to theoretical predictions, endothermic homeotherms can be classified
      as either thermal specialists or thermal generalists. In high cost environments,
      thermal specialists are supposed to be more prone to using facultative
      heterothermy than generalists. We tested this hypothesis at the intraspecific
      level using male laboratory mice (C57BL/cmdb) fasted under different thermal
      conditions (20 and 10 degrees C) and for different time periods (12-48 h). We
      predicted that variability of body temperature (Tb) and time spent with Tb below
      normothermy would increase with the increase of environmental demands (duration
      of fasting and cold). To verify the above prediction, we measured Tb and energy
      expenditure of fasted mice. We did not record torpor bouts but we found that
      variations in Tb and time spent in hypothermia increased with environmental
      demands. In response to fasting, mice also decreased their energy expenditure.
      Moreover, animals that showed more precise thermoregulation when fed had more
      variable Tb when fasted. We postulate that the prediction of the thermoregulatory
      generalist-specialist trade-off can be applied at the intraspecific level,
      offering a valid tool for identifying mechanistic explanations of the differences
      in animal responses to variations in energy supply.

PMID- 28432148
TI  - Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of
      Age: Cohort Study Using Electronic Health Records.
AB  - BACKGROUND: Clinical trials show benefit from lowering systolic blood pressure
      (SBP) in people >=80 years of age, but nonrandomized epidemiological studies
      suggest lower SBP may be associated with higher mortality. This study aimed to
      evaluate associations of SBP with all-cause mortality by frailty category >80
      years of age and to evaluate SBP trajectories before death. METHODS: A population
      based cohort study was conducted using electronic health records of 144 403
      participants >=80 years of age registered with family practices in the United
      Kingdom from 2001 to 2014. Participants were followed for <=5 years. Clinical
      records of SBP were analyzed. Frailty status was classified using the e-Frailty
      Index into the categories of fit, mild, moderate, and severe. All-cause mortality
      was evaluated by frailty status and mean SBP in Cox proportional-hazards models.
      SBP trajectories were evaluated using person months as observations, with mean
      SBP and antihypertensive treatment status estimated for each person month.
      Fractional polynomial models were used to estimate SBP trajectories over 5 years
      before death. RESULTS: During follow-up, 51 808 deaths occurred. Mortality rates
      increased with frailty level and were greatest at SBP <110 mm Hg. In fit women,
      mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110
      to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates
      were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated
      decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were
      higher in the last 3 months of life than 5 years previously in both treated (odds
      ratio, 6.06; 95% confidence interval, 5.40-6.81) and untreated (odds ratio, 6.31;
      95% confidence interval, 5.30-7.52) patients. There was no evidence of
      intensification of antihypertensive therapy in the final 2 years of life.
      CONCLUSIONS: A terminal decline of SBP in the final 2 years of life suggests that
      nonrandomized epidemiological associations of low SBP with higher mortality may
      be accounted for by reverse causation if participants with lower blood pressure
      values are closer, on average, to the end of life.

PMID- 28432151
TI  - Dehydration enhances multiple physiological defense mechanisms in a desert
      lizard, Heloderma suspectum.
AB  - The physiological challenges associated with dehydration can induce an increase
      in plasma glucocorticoid concentrations, a response thought to provide the
      mechanism for dehydration suppressing immune function. However, a comprehensive
      examination of the inter-relationship of dehydration, stress and immune function
      has not been conducted within a single species. We previously demonstrated that
      Gila monsters (Heloderma suspectum), which inhabit a xeric environment with a
      predictable seasonal drought, have enhanced measures of innate immunity when
      dehydrated. These results suggest that, in this species, dehydration may not
      induce a glucocorticoid response, but, instead, enhances physiological defense
      mechanisms. To explore this possibility, we examined multiple measures of innate
      immunity as well as initial and reactive plasma concentrations of glucocorticoids
      in captive and free-ranging Gila monsters at various hydration states. Our
      results show that, in this species, dehydration alone does not cause a
      substantial increase in plasma glucocorticoids, and we provide broader evidence
      that dehydration enhances defensive mechanisms including stress reactivity and
      various measures of innate immune function. These findings suggest that
      physiological responses to dehydration may depend heavily on an organism's
      ecology. More research on the effects of dehydration on the glucocorticoid
      response and immunity will help clarify the interactive roles they play in
      response to hydration challenges and whether adaptations to water-limited
      environments influence these interactions.

PMID- 28432153
TI  - Comparison of functional and anatomical estimations of visual acuity in two
      species of coral reef fish.
AB  - The high-contrast, complex patterns typical of many reef fish serve several
      purposes, including providing disruptive camouflage and a basis for vision-based
      communication. In trying to understand the role of a specific pattern, it is
      important to first assess the extent to which an observer can resolve the
      pattern, itself determined, at least in part, by the observer's visual acuity.
      Here, we studied the visual acuity of two species of reef fish - Pomacentrus
      amboinensis and Pseudochromis fuscus - using both anatomical and behavioural
      estimates. The two species share a common habitat but are members of different
      trophic levels (predator versus herbivore/omnivore) and perform different visual
      tasks. On the basis of the anatomical study, we estimated visual acuity to lie
      between 4.1 and 4.6 cycles deg-1 for P. amboinensis and 3.2 and 3.6 cycles deg-1
      for P. fuscus Behavioural acuity estimates were considerably lower, ranging
      between 1.29 and 1.36 cycles deg-1 for P. amboinensis and 1.61 and 1.71 cycles
      deg-1 for P. fuscus Our results show that two species from the same habitat have
      only moderately divergent visual capabilities, despite differences in their
      general life histories. The difference between anatomical and behavioural
      estimates is an important finding as the majority of our current knowledge on the
      resolution capabilities of reef fish comes from anatomical measurements. Our
      findings suggest that anatomical estimates may represent the highest potential
      acuity of fish but are not indicative of actual performance, and that there is
      unlikely to be a simple scaling factor to link the two measures across all fish
      species.

PMID- 28432152
TI  - Exposure to seawater increases intestinal motility in euryhaline rainbow trout
      (Oncorhynchus mykiss).
AB  - Upon exposure to seawater, euryhaline teleosts need to imbibe and desalinate
      seawater to allow for intestinal ion and water absorption, as this is essential
      for maintaining osmotic homeostasis. Despite the potential benefits of increased
      mixing and transport of imbibed water for increasing the efficiency of absorptive
      processes, the effect of water salinity on intestinal motility in teleosts
      remains unexplored. By qualitatively and quantitatively describing in vivo
      intestinal motility of euryhaline rainbow trout (Oncorhynchus mykiss), this study
      demonstrates that, in freshwater, the most common motility pattern consisted of
      clusters of rhythmic, posteriorly propagating contractions that lasted ~1-2 min
      followed by a period of quiescence lasting ~4-5 min. This pattern closely
      resembles mammalian migrating motor complexes (MMCs). Following a transition to
      seawater, imbibed seawater resulted in a significant distension of the intestine
      and the frequency of MMCs increased twofold to threefold with a concomitant
      reduction in the periods of quiescence. The increased frequency of MMCs was also
      accompanied by ripple-type contractions occurring every 12-60 s. These findings
      demonstrate that intestinal contractile activity of euryhaline teleosts is
      dramatically increased upon exposure to seawater, which is likely part of the
      overall response for maintaining osmotic homeostasis as increased drinking and
      mechanical perturbation of fluids is necessary to optimise intestinal ion and
      water absorption. Finally, the temporal response of intestinal motility in
      rainbow trout transitioning from freshwater to seawater coincides with previously
      documented physiological modifications associated with osmoregulation and may
      provide further insight into the underlying reasons shaping the migration
      patterns of salmonids.

PMID- 28432154
TI  - Identification of the septate junction protein gliotactin in the mosquito Aedes
      aegypti: evidence for a role in increased paracellular permeability in larvae.
AB  - Septate junctions (SJs) regulate paracellular permeability across invertebrate
      epithelia. However, little is known about the function of SJ proteins in aquatic
      invertebrates. In this study, a role for the transmembrane SJ protein gliotactin
      (Gli) in the osmoregulatory strategies of larval mosquito (Aedes aegypti) was
      examined. Differences in gli transcript abundance were observed between the
      midgut, Malpighian tubules, hindgut and anal papillae of A. aegypti, which are
      epithelia that participate in larval mosquito osmoregulation. Western blotting of
      Gli revealed its presence in monomer, putative dimer and alternatively processed
      protein forms in different larval mosquito organs. Gli localized to the entire SJ
      domain between midgut epithelial cells and showed a discontinuous localization
      along the plasma membranes of epithelial cells of the rectum as well as the
      syncytial anal papillae epithelium. In the Malpighian tubules, Gli
      immunolocalization was confined to SJs between the stellate and principal cells.
      Rearing larvae in 30% seawater caused an increase in Gli protein abundance in the
      anterior midgut, Malpighian tubules and hindgut. Transcriptional knockdown of gli
      using dsRNA reduced Gli protein abundance in the midgut and increased the flux
      rate of the paracellular permeability marker, polyethylene glycol (molecular
      weight 400 Da; PEG-400). Data suggest that in larval A. aegypti, Gli participates
      in the maintenance of salt and water balance and that one role for Gli is to
      participate in the regulation of paracellular permeability across the midgut of
      A. aegypti in response to changes in environmental salinity.

PMID- 28432155
TI  - Interactive effects of oxygen, carbon dioxide and flow on photosynthesis and
      respiration in the scleractinian coral Galaxea fascicularis.
AB  - Rates of dark respiration and net photosynthesis were measured for six replicate
      clonal fragments of the stony coral Galaxea fascicularis (Linnaeus 1767), which
      were incubated under 12 different combinations of dissolved oxygen (20%, 100% and
      150% saturation), dissolved carbon dioxide (9.5 and 19.1 umol l-1) and water flow
      (1-1.6 versus 4-13 cm s-1) in a repeated measures design. Dark respiration was
      enhanced by increased flow and increased oxygen saturation in an interactive way,
      which relates to improved oxygen influx into the coral tissue. Oxygen saturation
      did not influence net photosynthesis: neither hypoxia nor hyperoxia affected net
      photosynthesis, irrespective of flow and pH, which suggests that hyperoxia does
      not induce high rates of photorespiration in this coral. Flow and pH had a
      synergistic effect on net photosynthesis: at high flow, a decrease in pH
      stimulated net photosynthesis by 14%. These results indicate that for this
      individual of G. fascicularis, increased uptake of carbon dioxide rather than
      increased efflux of oxygen explains the beneficial effect of water flow on
      photosynthesis. Rates of net photosynthesis measured in this study are among the
      highest ever recorded for scleractinian corals and confirm a strong scope for
      growth.

PMID- 28432156
TI  - Epidemiology of valvular heart disease in a Swedish nationwide hospital-based
      register study.
AB  - OBJECTIVE: Transitions in the spectrum of valvular heart diseases (VHDs) in
      developed countries over the 20th century have been reported from clinical case
      series, but large, contemporary population-based studies are lacking. METHODS: We
      used nationwide registers to identify all patients with a first diagnosis of VHD
      at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified
      incidence of each VHD and adjusted comorbidity profiles were assessed. RESULTS:
      In the Swedish population (n=10 164 211), the incidence of VHD was 63.9 per 100
      000 person-years, with aortic stenosis (AS; 47.2%), mitral regurgitation (MR;
      24.2%) and aortic regurgitation (AR; 18.0%) contributing most of the VHD
      diagnoses. The majority of VHDs were diagnosed in the elderly (68.9% in subjects
      aged >=65 years), but pulmonary valve disease incidence peaked in newborns.
      Incidences of AR, AS and MR were higher in men who were also more frequently
      diagnosed at an earlier age. Mitral stenosis (MS) incidence was higher in women.
      Rheumatic fever was rare. Half of AS cases had concomitant atherosclerotic
      vascular disease (48.4%), whereas concomitant heart failure and atrial
      fibrillation were common in mitral valve disease and tricuspid regurgitation.
      Other common comorbidities were thoracic aortic aneurysms in AR (10.3%),
      autoimmune disorders in MS (24.5%) and abdominal hernias or prolapse in MR
      (10.7%) and TR (10.3%). CONCLUSIONS: Clinically diagnosed VHD was primarily a
      disease of the elderly. Rheumatic fever was rare in Sweden, but specific VHDs
      showed a range of different comorbidity profiles . Pronounced sex-specific
      patterns were observed for AR and MS, for which the mechanisms remain
      incompletely understood.

PMID- 28432157
TI  - Effect of interleukin-6 inhibition on coronary microvascular and endothelial
      function in myocardial infarction.
AB  - OBJECTIVE: Interleukin-6 (IL-6) is a driver of inflammation and associated
      endothelial cell activation in acute coronary syndromes. We evaluated the effect
      of the IL-6 receptor antagonist tocilizumab on coronary microvascular function
      and endothelial dysfunction measured by coronary flow reserve (CFR) and markers
      of endothelial cell activation in patients with non-ST-elevation myocardial
      infarction (NSTEMI). METHODS: This substudy was part of a two-centre, double
      blind, randomised, placebo-controlled trial evaluating the effect of a single
      dose of tocilizumab in NSTEMI. Markers of endothelial cell activation (vascular
      cell adhesion molecule (VCAM)-1, intercellular adhesion molecule-1 and von
      Willebrand factor) were assessed in 117 patients. In 42 of these patients, 20
      assigned to placebo and 22 to tocilizumab, we measured CFR. Blood samples were
      obtained at seven consecutive time points between day 1 and 3. CFR was measured
      by transthoracic echocardiography during hospitalisation and after 6 months.
      RESULTS: Tocilizumab did not affect CFR during hospitalisation (tocilizumab:
      3.4+/-0.8 vs placebo: 3.3+/-1.2, p=0.80). CFR improved significantly in both
      groups at 6 months. Patients in the tocilizumab group had significantly higher
      area under the curve for VCAM-1 (median 622 vs 609 ng/mL/hour, tocilizumab and
      placebo respectively, p=0.003). There were inverse correlations between VCAM-1
      and CFR in the placebo (hospitalisation: r=-0.74, p<0.01, 6 months: r=-0.59,
      p<0.01), but not in the tocilizumab group (hospitalisation: r=0.20, p=0.37, 6
      months r=-0.28, p=0.20). CONCLUSIONS: Tocilizumab did not affect CFR during
      hospitalisation or after 6 months. Tocilizumab increased VCAM-1 levels during
      hospitalisation, but this was not associated with reduced CFR in these patients.

PMID- 28432158
TI  - Risk score for cardiac surgery in active left-sided infective endocarditis.
AB  - OBJECTIVE: To develop and validate a calculator to predict the risk of in
      hospital mortality in patients with active infective endocarditis (IE) undergoing
      cardiac surgery. METHODS: Thousand two hundred and ninety-nine consecutive
      patients with IE were prospectively recruited (1996-2014) and retrospectively
      analysed. Left-sided patients who underwent cardiac surgery (n=671) form our
      study population and were randomised into development (n=424) and validation
      (n=247) samples. Variables statistically significant to predict in-mortality were
      integrated in a multivariable prediction model, the Risk-Endocarditis Score (RISK
      E). The predictive performance of the score and four existing surgical scores
      (European System for Cardiac Operative Risk Evaluation (EuroSCORE) I and II),
      Prosthesis, Age >=70, Large Intracardiac Destruction, Staphylococcus, Urgent
      Surgery, Sex (Female) (PALSUSE), EuroSCORE >=10) and Society of Thoracic
      Surgeons's Infective endocarditis score (STS-IE)) were assessed and compared in
      our cohort. Finally, an external validation of the RISK-E in a separate
      population was done. RESULTS: Variables included in the final model were age,
      prosthetic infection, periannular complications, Staphylococcus aureus or fungi
      infection, acute renal failure, septic shock, cardiogenic shock and
      thrombocytopaenia. Area under the receiver operating characteristic curve in the
      validation sample was 0.82 (95% CI 0.75 to 0.88). The accuracy of the other
      surgical scores when compared with the RISK-E was inferior (p=0.010). Our score
      also obtained a good predictive performance, area under the curve 0.76 (95% CI
      0.64 to 0.88), in the external validation. CONCLUSIONS: IE-specific factors
      (microorganisms, periannular complications and sepsis) beside classical variables
      in heart surgery (age, haemodynamic condition and renal failure) independently
      predicted perioperative mortality in IE. The RISK-E had better ability to predict
      surgical mortality in patients with IE when compared with other surgical scores.

PMID- 28432159
TI  - A middle-aged woman with a heavy heart.

PMID- 28432160
TI  - Infective endocarditis in octogenarians.
AB  - OBJECTIVE: To describe the characteristics of infective endocarditis (IE) in
      octogenarians and assess their prognosis. METHODS: Patients with definite IE
      hospitalised at a referral centre between July 2008 and July 2013 were
      prospectively included. A total of 454 patients were divided into three groups:
      230 patients under 65 years old, 173 patients between 65 and 80 years old, and 51
      patients over 80 years old. The main end point was 1-year mortality. RESULTS: One
      year mortality was higher in the >=80 years old group (37.3%) than in the <65
      years old group (13%; p<0.001) and the 65-80 years old group (19.7%; p=0.009).
      Enterococci and Streptococcus gallolyticus were the more frequent micro
      organisms. Embolism under antibiotic therapy (n=11 (21.6%), p=0.03) and renal
      failure (n=23 (51%), p=0.004) were more frequent in the >=80 years old group.
      Among the >=80 years old group, 38 patients had theoretical indication for
      surgery. Mortality was low (6.3%) in the 16 operated patients, but very high
      (72.7%) in the 22 patients not operated. Even if octogenarians were less often
      operated, their survival after surgery was excellent like younger patients
      (93.7%, 89.9% and 90.4%, respectively), whereas the absence of surgery was
      associated with very poor prognosis. CONCLUSIONS: IE in octogenarians is a
      different disease, with Enterococci as the most frequent micro-organisms and with
      higher mortality than younger patients. ESC recommendations for surgery are less
      implemented than in younger patients, yielding dramatic mortality in patients not
      operated despite a theoretical indication for surgery, while operated patients
      have an excellent prognosis. These results suggest that surgery is underused in
      octogenarians.

PMID- 28432161
TI  - Aggregatibacter actinomycetemcomitans pneumonia with chest and abdominal wall
      involvement.
AB  - A 54-year-old man presented with a productive cough, chest pain, fever and weight
      loss. Initial analysis revealed a palpable chest wall mass and consolidation in
      the left lower lobe and pleural abnormalities on imaging. At that point no
      infectious cause or malignancy was identified. Microbiological analysis of a
      needle biopsy from a newly developed abdominal wall mass revealed growth of
      Aggregatibacter actinomycetemcomitans The patient was successfully treated with
      antibiotic therapy for 1 year. Aggregatibacter actinomycetemcomitans is a Gram
      negative coccobacillus and is part of the normal oral flora. It is capable of
      causing infections in humans including periodontitis, soft tissue abscesses and
      systemic invasive infections, most commonly endocarditis.

PMID- 28432162
TI  - Conventional transanal excision for a very low gastrointestinal stromal tumour.
AB  - Gastrointestinal stromal tumour (GIST) represents a rare tumour entity, which has
      been more intensively investigated during the last decade. The rectum as the
      primary site of GIST is even uncommon. The space constraints in the pelvis
      renders optimal oncological surgery demanding and proximity of these lesions to
      the anal sphincter enhances the potential morbidity of any radical surgery. We
      herein report on a young patient with a >5 cm rectal GIST localised at 1 cm from
      the anorectal junction.

PMID- 28432163
TI  - An unusually large onychomatricoma.
AB  - Onychomatricoma is a rare benign tumour of the nail matrix first described in
      1992, and since then, no more than 80 cases have been reported. Despite distinct
      clinical characteristics, it is frequently misdiagnosed as onychomycosis partly
      due to remaining an unknown entity. The authors present the case of a patient
      with a 30-year history of nail abnormalities with more recent growth to alarming
      dimensions.

PMID- 28432164
TI  - Use of gabapentin in the treatment of chronic pain in an adolescent with sickle
      cell disease.
AB  - Vaso-occlusive crises are the most common manifestation of sickle cell disease
      (SCD) and the main cause of hospital admission in these patients. There is
      emerging evidence that vaso-occlusive pain has both nociceptive and neuropathic
      components. However, the treatment of SCD-related pain with neuropathic drugs has
      not yet been systematically studied, particularly in children. We describe a 14
      year-old girl with SCD and multiple hospital admissions for pain management for
      severe acute vaso-occlusive pain episodes. The patient was evaluated by a
      multidisciplinary team of specialists which considered that the chronic,
      refractory pain she was experiencing for years was probably neuropathic in origin
      and it was decided to start oral gabapentin (300 mg/day). At 10 months follow-up,
      the patient reported remarkable improvement in her quality of life with a
      significant decrease in the number of hospital admissions (three admissions for
      acute vaso-occlusive pain episodes in 10 months versus the previously monthly
      recurrences).

PMID- 28432165
TI  - Intravitreal cysticercosis with full thickness macular hole: management outcome
      and intraoperative optical coherence tomography features.
AB  - Ocular cysticercosis is a serious condition with a potential for complete vision
      loss if left untreated. Intravitreal cysticercosis is the most common ocular form
      of cysticercosis and is associated with retinal detachment, retinal traction,
      subretinal scarring and vitritis. To the best of our knowledge, there is no
      report of the occurrence of a live intravitreal cysticercosis with a full
      thickness macular hole (FTMH) in the literature. We here report a case of live
      intravitreal cysticercosis with a FTMH along with its management and
      intraoperative optical coherence tomography features of the live cysticercus.

PMID- 28432166
TI  - The Lazarus phenomenon: spontaneous cardioversion after termination of
      resuscitation in a Scottish hospital.
AB  - A 66-year-old man suffered a ventricular fibrillation cardiac arrest after an
      episode of chest pain. Despite advanced life support, his condition deteriorated;
      the situation was considered irrecoverable and resuscitation was discontinued.
      The patient was observed for about 5 min with irregular agonal gasping
      respirations evident but no palpable pulse. A gradual increase in the regularity
      of breathing pattern heralded the return of spontaneous circulation. An inferior
      myocardial infarction was diagnosed. Primary percutaneous coronary intervention
      was performed. The patient was discharged from hospital after 9 days with no
      neurological sequelae. There are several possible mechanisms to explain the
      Lazarus phenomenon including auto-positive end expiratory pressure and delayed
      drug actions, but cases are rarely reported in the medical literature. After
      discontinued resuscitation, we suggest consideration should be given to a period
      of continued monitoring. However, evidence is limited and prospective studies
      would be welcome to allow firmer recommendations.

PMID- 28432167
TI  - A tale of two vasculitides: biopsy-proven giant cell arteritis followed by the
      independent development of renal-limited microscopic polyangiitis.
AB  - We describe an 80-year-old woman who presented with headaches, bilateral jaw
      claudication and visual symptoms. She was diagnosed with giant cell arteritis,
      which was confirmed by temporal artery biopsy. She was treated with high-dose
      prednisone followed by a slow taper, with complete resolution of symptoms.
      Approximately 4 years later, she developed progressively worsening renal function
      associated with haematuria. Serological workup revealed a high-titre perinuclear
      antinuclear cytoplasmic antibody and antibodies to myeloperoxidase. Renal biopsy
      demonstrated a pauci-immune focal crescentic glomerulonephritis. Extensive review
      of systems, physical exam and diagnostic studies demonstrated no evidence of
      extra-renal disease, and she was diagnosed with renal-limited microscopic
      polyangiitis. High-dose prednisone was resumed, but she refused treatment with
      either cyclophosphamide or rituximab due to concern for toxicity. Her prednisone
      dose was tapered and renal function stabilised. Our case highlights the need to
      recognise the successive occurrence of two distinct vasculitides in a single
      patient and monitor accordingly.

PMID- 28432168
TI  - Ultrasound-B scan: an indispensable tool for diagnosing ocular cysticercosis.

PMID- 28432169
TI  - Primary malignant melanoma of the cervix: a rare disease.
AB  - Malignant melanoma (MM) arising primarily in the cervix is exceedingly rare and
      has a poor prognosis. We report the case of a primary MM of the cervix in a 64
      year-old woman with vaginal bleeding. She presented with a cervical amelanotic
      lesion which on biopsy rendered the diagnosis of MM. The patient was staged as
      International Federation of Gynecology and Obstetrics IIB and underwent Wertheim
      Meigshysterectomy followed by brachytherapy. One year later, she was diagnosed
      with a large pelvic relapse for which surgery was performed. She then presented
      with a vaginal relapse and an isolated hepatic lesion, both of which were
      proposed for surgery. The diagnosis of MM of the cervix is a clinical and
      pathological challenge due to its rarity and overlapping features. Cytology
      cannot accurately diagnose it. Moreover, amelanotic MMs must be distinguished
      from other poorly differentiated carcinomas by diagnosis that ultimately relies
      on immunohistochemical staining. Radical surgery is the only treatment showing
      predictive benefit.

PMID- 28432170
TI  - Calcified cauliflower ear in relapsing polychondritis.

PMID- 28432171
TI  - Ascites in a patient with episodic angio-oedema and eosinophilia: thinking
      outside the box.
AB  - Episodic angio-oedema with eosinophilia (EAE) or Gleich's syndrome is a rare
      condition characterised by recurrent episodes of oedema and eosinophilia,
      accompanied by urticaria, fever and weight gain. The presence of ascites has not
      been reported so far. We report a 21-year-old Caucasian woman who presented with
      marked ocular oedema and ascites. Laboratory evaluation revealed marked
      eosinophilia. During the last 3 months, three episodes of facial and neck oedema
      were reported, which resolved spontaneously over a period of 3-5 days. The
      diagnosis of EAE was established after exclusion of secondary causes (infections,
      allergic reactions, collagen diseases, neoplasms) and clonal disorders associated
      with marked eosinophilia. Low-dose steroids resulted in eosinophil decrease and
      complete resolution of symptoms, including ascites. This case highlights that
      ascites can be a very rare manifestation of EAE particularly if other more
      frequent causes of ascites have been excluded and the clinical and laboratory
      findings are supportive of EAE.

PMID- 28432172
TI  - Why tuberculosis control programmes fail? Role of microlevel and macrolevel
      factors: an analysis from India.
AB  - India accounts for one-fourth of the global tuberculosis (TB) burden. The
      National TB Program was started in 1962. Over a period of time, some lacunae such
      as poor case detection rate and incomplete treatment were observed. Later, the
      government formulated the Revised National Tuberculosis Control Program (RNTCP),
      which achieved a case detection rate of 70% and a cure rate of 85%. Still, the
      problem of relapse and defaulter cases persists. In 2014, 6% defaulter cases were
      reported from India. RNTCP has also focused on microlevel aspects, that is, newer
      diagnostics such as GenXpert, line probe assay and medicines such as bedaquiline
      for drug-resistant TB. Action on the macrolevel aspects, for example, social
      determinants, is ignored. This is natural because these are out of the purview of
      the health sector. This case study reflects how a resident doctor in a rural
      clinic of North India tried to resolve the macrolevel and microlevel issues
      pertaining to defaulter TB cases.

PMID- 28432173
TI  - Successful treatment of squamous cell carcinoma of the lip with electron beam
      therapy: a symphony of medicine and physics.

PMID- 28432174
TI  - Postintervention acute opsoclonus myoclonus syndrome.
AB  - Opsoclonus myoclonus syndrome (OMS) is a rare, neurological condition affecting 1
      in 10 000 000 people annually. Opsoclonus, defined as involuntary rapid,
      multivectorial oscillations of the eyes, together with ataxia and myoclonus are
      usually present. OMS may be paraneoplastic: often associated with occult
      neuroblastoma in childhood and with breast carcinoma or small cell lung carcinoma
      in adults. Other aetiologies include viral or toxic agents. The pathogenesis is
      thought to be immune mediated. A 37-year-old woman with previous inflammatory
      cranial mononeuropathies was admitted for elective dilatation and curettage
      (D&C). Immediately after she complained of left-sided paraesthesia and later
      became disoriented, with incoherent speech, inability to obey commands,
      opsoclonus of the eyes and myoclonic jerks. Investigations including onconeuronal
      antibodies, cerebrospinal fluid analysis, and imaging were normal. She was
      treated with intravenous methylprednisolone with rapid improvement. Previous
      surgeries with anaesthesia were uncomplicated. The anaesthetic agents used for
      the D&C were fentanyl and propofol.

PMID- 28432175
TI  - Arterial spin-labelled perfusion MRI demonstrates early spontaneous
      recanalisation of clot after cardiogenic embolism.

PMID- 28432176
TI  - A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients
      with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.
AB  - Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011),
      displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor
      (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and
      recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary
      activity of single-agent ribociclib were investigated in pediatric patients with
      neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered
      tumors.Experimental Design: Patients (aged 1-21 years) received escalating once
      daily oral doses of ribociclib (3-weeks-on/1-week-off). Dose escalation was
      guided by a Bayesian logistic regression model with overdose control and real
      time PK.Results: Thirty-two patients (median age, 5.5 years) received ribociclib
      280, 350, or 470 mg/m2 Three patients had dose-limiting toxicities of grade 3
      fatigue (280 mg/m2; n = 1) or grade 4 thrombocytopenia (470 mg/m2; n = 2). Most
      common treatment-related adverse events (AE) were hematologic: neutropenia (72%
      all-grade/63% grade 3/4), leukopenia (63%/38%), anemia (44%/3%), thrombocytopenia
      (44%/28%), and lymphopenia (38%/19%), followed by vomiting (38%/0%), fatigue
      (25%/3%), nausea (25%/0%), and QTc prolongation (22%/0%). Ribociclib exposure was
      dose-dependent at 350 and 470 mg/m2 [equivalent to 600 (RP2D)-900 mg in adults],
      with high interpatient variability. Best overall response was stable disease (SD)
      in nine patients (seven with neuroblastoma, two with primary CNS MRT); five
      patients achieved SD for more than 6, 6, 8, 12, and 13 cycles,
      respectively.Conclusions: Ribociclib demonstrated acceptable safety and PK in
      pediatric patients. MTD (470 mg/m2) and RP2D (350 mg/m2) were equivalent to those
      in adults. Observations of prolonged SD support further investigation of
      ribociclib combined with other agents in neuroblastoma and MRT. Clin Cancer Res;
      23(10); 2433-41. (c)2017 AACR.

PMID- 28432177
TI  - A peptide adhesive molded by magnesium glues Rubisco's subunits together.
AB  - Rubisco enzymes play central roles in carbon fixation, with potential importance
      in biotechnology, but have eluded a full description of their multistep assembly
      and function. A new article describes the fascinating discovery that some
      archaeal Rubiscos contain a built-in assembly domain inserted into an otherwise
      canonical Rubisco fold, providing a tremendous expansion of our understanding of
      the diversity of naturally occurring Rubiscos.

PMID- 28432178
TI  - JBC is on a mission to facilitate scientific discovery.

PMID- 28432179
TI  - Three doctors struck off for dishonesty are allowed back on medical register.

PMID- 28432180
TI  - New York University sacks professor for refusing flu shot.

PMID- 28432182
TI  - Toward a direct and scalable identification of reduced models for categorical
      processes.
AB  - The applicability of many computational approaches is dwelling on the
      identification of reduced models defined on a small set of collective variables
      (colvars). A methodology for scalable probability-preserving identification of
      reduced models and colvars directly from the data is derived-not relying on the
      availability of the full relation matrices at any stage of the resulting
      algorithm, allowing for a robust quantification of reduced model uncertainty and
      allowing us to impose a priori available physical information. We show two
      applications of the methodology: (i) to obtain a reduced dynamical model for a
      polypeptide dynamics in water and (ii) to identify diagnostic rules from a
      standard breast cancer dataset. For the first example, we show that the obtained
      reduced dynamical model can reproduce the full statistics of spatial molecular
      configurations-opening possibilities for a robust dimension and model reduction
      in molecular dynamics. For the breast cancer data, this methodology identifies a
      very simple diagnostics rule-free of any tuning parameters and exhibiting the
      same performance quality as the state of the art machine-learning applications
      with multiple tuning parameters reported for this problem.

PMID- 28432181
TI  - Dual nature of pseudouridylation in U2 snRNA: Pus1p-dependent and Pus1p
      independent activities in yeasts and higher eukaryotes.
AB  - The pseudouridine at position 43 in vertebrate U2 snRNA is one of the most
      conserved post-transcriptional modifications of spliceosomal snRNAs; the
      equivalent position is pseudouridylated in U2 snRNAs in different phyla including
      fungi, insects, and worms. Pseudouridine synthase Pus1p acts alone on U2 snRNA to
      form this pseudouridine in yeast Saccharomyces cerevisiae and mouse. Furthermore,
      in S. cerevisiae, Pus1p is the only pseudouridine synthase for this position.
      Using an in vivo yeast cell system, we tested enzymatic activity of Pus1p from
      the fission yeast Schizosaccharomyces pombe, the worm Caenorhabditis elegans, the
      fruit fly Drosophila melanogaster, and the frog Xenopus tropicalis We
      demonstrated that Pus1p from C. elegans has no enzymatic activity on U2 snRNA
      when expressed in yeast cells, whereas in similar experiments, position 44 in
      yeast U2 snRNA (equivalent to position 43 in vertebrates) is a genuine substrate
      for Pus1p from S. cerevisiae, S. pombe, Drosophila, Xenopus, and mouse. However,
      when we analyzed U2 snRNAs from Pus1 knockout mice and the pus1Delta S. pombe
      strain, we could not detect any changes in their modification patterns when
      compared to wild-type U2 snRNAs. In S. pombe, we found a novel box H/ACA RNA
      encoded downstream from the RPC10 gene and experimentally verified its guide RNA
      activity for positioning Psi43 and Psi44 in U2 snRNA. In vertebrates, we showed
      that SCARNA8 (also known as U92 scaRNA) is a guide for U2-Psi43 in addition to
      its previously established targets U2-Psi34/Psi44.

PMID- 28432183
TI  - Anacetrapib-driven triglyceride lowering explained: the fortuitous role of CETP
      in the intravascular catabolism of triglyceride-rich lipoproteins.

PMID- 28432184
TI  - Management of a case of myopic foveoschisis with phakic intraocular lens (pIOL)
      in situ: intraoperative challenges.
AB  - We describe the case of a 30-year-old man with pathological myopia with a phakic
      intraocular lens (IOL) (Visian ICL V4c model; STAAR, Monrovia, California, USA)
      in situ having complaints of metamorphopsia in the left eye with documented
      myopic foveoschisis on swept-source optical coherence tomography (DRI OCT Triton;
      Topcon, Tokyo, Japan). The patient underwent pars plana vitrectomy with internal
      limiting membrane peeling. This report discusses the intraoperative challenges
      occurring as a result of increased optical aberrations in the presence of a
      phakic IOL.

PMID- 28432185
TI  - Exogenous Cushing's syndrome due to a Chinese herbalist's prescription of
      ointment containing dexamethasone.
AB  - Eczema in children is a chronic disabling condition. The impact of this condition
      on the lives of families is often underestimated by conventional physicians. As a
      consequence parents may investigate complementary treatment options. Close
      monitoring by a paediatrician is essential, considering that a variety of adverse
      effects can occur during the use of complementary treatment. We present a 5-year
      old girl with eczema. She visited a Chinese herbalist who prescribed an ointment.
      The parents noticed that the eczema resolved fast, itching decreased and she was
      finally sleeping well. However, her behaviour changed and appetite increased.
      Undetectable levels of serum cortisol were found, which was indicative of
      exogenous Cushing's syndrome. Analysis of the ointment revealed the presence of
      dexamethasone. Hydrocortisone substitution and subsequently a reduction schedule
      were implemented, after which endogenous cortisol production recovered after 4
      months. Physicians should be aware that unregistered herbal medicine can contain
      potent drugs such as glucocorticoids.

PMID- 28432186
TI  - Wellness Initiatives: Benefits and Limitations.

PMID- 28432187
TI  - Transesophageal echocardiographic guidance of transcatheter closure of the aortic
      valve in a patient with left ventricular assist device-related severe aortic
      regurgitation.

PMID- 28432188
TI  - Magnetic Resonance Neurography Visualizes Abnormalities in Sciatic and Tibial
      Nerves in Patients With Type 1 Diabetes and Neuropathy.
AB  - This study evaluates whether diffusion tensor imaging magnetic resonance
      neurography (DTI-MRN), T2 relaxation time, and proton spin density can detect and
      grade neuropathic abnormalities in patients with type 1 diabetes. Patients with
      type 1 diabetes (n = 49) were included-11 with severe polyneuropathy (sDPN), 13
      with mild polyneuropathy (mDPN), and 25 without polyneuropathy (nDPN)-along with
      30 healthy control subjects (HCs). Clinical examinations, nerve conduction
      studies, and vibratory perception thresholds determined the presence and severity
      of DPN. DTI-MRN covered proximal (sciatic nerve) and distal (tibial nerve) nerve
      segments of the lower extremity. Fractional anisotropy (FA) and the apparent
      diffusion coefficient (ADC) were calculated, as were T2 relaxation time and
      proton spin density obtained from DTI-MRN. All magnetic resonance findings were
      related to the presence and severity of neuropathy. FA of the sciatic and tibial
      nerves was lowest in the sDPN group. Corresponding with this, proximal and distal
      ADCs were highest in patients with sDPN compared with patients with mDPN and
      nDPN, as well as the HCs. DTI-MRN correlated closely with the severity of
      neuropathy, demonstrating strong associations with sciatic and tibial nerve
      findings. Quantitative group differences in proton spin density were also
      significant, but less pronounced than those for DTI-MRN. In conclusion, DTI-MRN
      enables detection in peripheral nerves of abnormalities related to DPN, more so
      than proton spin density or T2 relaxation time. These abnormalities are likely to
      reflect pathology in sciatic and tibial nerve fibers.

PMID- 28432190
TI  - A single-centre hospital-wide handoff standardisation report: what is so special
      about that?

PMID- 28432189
TI  - Safety and efficiency of a new generic package labelling: a before and after
      study in a simulated setting.
AB  - BACKGROUND: Medication errors are frequent and may cause harm to patients and
      increase healthcare expenses. AIM: To explore whether a new labelling influences
      time and errors when preparing medications in accordance with medication charts
      in an experimental setting. METHOD: We carried out an uncontrolled before and
      after study with 3 months inbetween experiments. Phase I used original labelling
      and phase II used new generic labelling. We set up an experimental medicine room,
      simulating a real-life setting. Twenty-five nurses and ten pharmacy technicians
      participated in the study. We asked them to prepare medications in accordance
      with medication charts, place packages on a desk and document the package
      prepared. We timed the operation. Participants were asked to prepare medications
      in accordance with as many charts as possible within 30 min. RESULTS: Nurses
      prepared significantly more medication charts with the generic labelling compared
      with the original 3.3 versus 2.6 (p=0.009). Mean time per medication chart was
      significantly lower with the generic labelling 6.9 min/chart versus 8.5 min/chart
      (p<0.001). Pharmacy technicians were significantly faster than the nurses in both
      phase I (6.8 min/chart vs 9.5 min/chart; p<0.001) and phase II (6.1 min/chart vs
      7.2 min/chart; p=0.013). The number of errors was low and not significantly
      different between the two labellings, with errors affecting 9.1% of charts in
      phase I versus 6.5% in phase II (p=0.5). CONCLUSIONS: A new labelling of
      medication packages with prominent placement of the active substance(s) and
      strength(s) in the front of the medication package may reduce time for nurses
      when preparing medications, without increasing medication errors.

PMID- 28432192
TI  - Evidence that avian influenza vaccination induces long-lived immune responses in
      zoo birds.

PMID- 28432191
TI  - Gene expression effects of glucocorticoid and mineralocorticoid receptor agonists
      and antagonists on normal human skeletal muscle.
AB  - Mineralocorticoid and glucocorticoid receptors are closely related steroid
      hormone receptors that regulate gene expression through many of the same hormone
      response elements. However, their transcriptional activities and effects in
      skeletal muscles are largely unknown. We recently identified mineralocorticoid
      receptors (MR) in skeletal muscles after finding that combined treatment with the
      angiotensin-converting enzyme inhibitor lisinopril and MR antagonist
      spironolactone was therapeutic in Duchenne muscular dystrophy mouse models. The
      glucocorticoid receptor (GR) agonist prednisolone is the current standard-of-care
      treatment for Duchenne muscular dystrophy because it prolongs ambulation, likely
      due to its anti-inflammatory effects. However, data on whether glucocorticoids
      have a beneficial or detrimental direct effect on skeletal muscle are
      controversial. Here, we begin to define the gene expression profiles in normal
      differentiated human skeletal muscle myotubes treated with MR and GR agonists and
      antagonists. The MR agonist aldosterone and GR agonist prednisolone had highly
      overlapping gene expression profiles, supporting the notion that prednisolone
      acts as both a GR and MR agonist that may have detrimental effects on skeletal
      muscles. Co-incubations with aldosterone plus either nonspecific or selective MR
      antagonists, spironolactone or eplerenone, resulted in similar numbers of gene
      expression changes, suggesting that both drugs can block MR activation to a
      similar extent. Eplerenone treatment alone decreased a number of important muscle
      specific genes. This information may be used to develop biomarkers to monitor
      clinical efficacy of MR antagonists or GR agonists in muscular dystrophy, develop
      a temporally coordinated treatment with both drugs, or identify novel
      therapeutics with more specific downstream targets.

PMID- 28432193
TI  - Randomised positive control trial of NSAID and antimicrobial treatment for calf
      fever caused by pneumonia.
AB  - One hundred and fifty-four preweaning calves were followed between May and
      October2015. Calves were fitted with continuous monitoring temperature probes
      (TempVerifiedFeverTag), programmed so a flashing light emitting diode (LED) light
      was triggered followingsix hours of a sustained ear canal temperature of >=39.7
      degrees C. A total of 83 calves (61.9 percent) developed undifferentiated fever,
      with a presumptive diagnosis of pneumonia throughexclusion of other calf
      diseases. Once fever was detected, calves were randomly allocatedto treatment
      groups. Calves in group 1 (NSAID) received 2 mg/kg flunixin meglumine(Allevinix,
      Merial) for three consecutive days and group 2 (antimicrobial) received 6
      mg/kggamithromycin (Zactran, Merial). If fever persisted for 72 hours after the
      initial treatment,calves were given further treatment (group 1 received
      antimicrobial and group 2 receivedNSAID). Calves in group 1 (NSAID) were five
      times more likely (P=0.002) to require a secondtreatment (the antimicrobial)
      after 72 hours to resolve the fever compared with the needto give group 2
      (antimicrobial) calves a second treatment (NSAID). This demonstratesthe
      importance of ongoing monitoring and follow-up of calves with respiratory
      disease.However, of calves with fever in group 1 (NSAID), 25.7 per cent showed
      resolution followingNSAID-only treatment with no detrimental effect on the
      development of repeated fever ordaily live weight gain. This suggests that NSAID
      alone may be a useful first-line treatment,provided adequate attention is given
      to ongoing monitoring to identify those cases thatrequire additional
      antimicrobial treatment.

PMID- 28432194
TI  - Diagnostic value of prehospital ECG in acute stroke patients.
AB  - OBJECTIVE: To investigate the diagnostic yield of prehospital ECG monitoring
      provided by emergency medical services in the case of suspected stroke. METHODS:
      Consecutive patients with acute stroke admitted to our tertiary stroke center via
      emergency medical services and with available prehospital ECG were prospectively
      included during a 12-month study period. We assessed prehospital ECG recordings
      and compared the results to regular 12-lead ECG on admission and after continuous
      ECG monitoring at the stroke unit. RESULTS: Overall, 259 patients with
      prehospital ECG recording were included in the study (90.3% ischemic stroke, 9.7%
      intracerebral hemorrhage). Atrial fibrillation (AF) was detected in 25.1% of
      patients, second-degree or greater atrioventricular block in 5.4%, significant ST
      segment elevation in 5.0%, and ventricular ectopy in 9.7%. In 18 patients, a
      diagnosis of new-onset AF with direct clinical consequences for the evaluation
      and secondary prevention of stroke was established by the prehospital recordings.
      In 2 patients, the AF episodes were limited to the prehospital period and were
      not detected by ECG on admission or during subsequent monitoring at the stroke
      unit. Of 126 patients (48.6%) with relevant abnormalities in the prehospital ECG,
      16.7% received medical antiarrhythmic therapy during transport to the hospital,
      and 6.4% were transferred to a cardiology unit within the first 24 hours in the
      hospital. CONCLUSIONS: In a selected cohort of patients with stroke, the in-field
      recordings of the ECG detected a relevant rate of cardiac arrhythmia. The results
      can add to the in-hospital evaluation and should be considered in prehospital
      care of acute stroke.

PMID- 28432196
TI  - The case against libertarian arguments for compulsory vaccination.
AB  - In a recent paper in this journal, Jason Brennan correctly notes that
      libertarians struggle to justify a policy of compulsory vaccination. The most
      straightforward argument that justifies compulsory vaccination is that such a
      policy promotes welfare. But libertarians cannot make this argument because they
      claim that the state is justified only in protecting negative rights, not in
      promoting welfare. I consider two representative libertarian attempts to justify
      compulsory vaccination, and I argue that such arguments are unsuccessful. They
      either fail to show that the state is justified in implementing the policy or
      overgeneralise. I suggest that Brennan's solution is especially well motivated
      insofar as it addresses the shortcomings of these arguments. Brennan argues that
      we violate the rights of others by participating in an activity that imposes an
      unacceptable collective risk of harm. Going unvaccinated is an activity that
      imposes an unacceptable collective risk of harm, and thus amounts to a rights
      violation. So, the state can implement a policy of compulsory vaccination I
      object, however, that Brennan's delineation of acceptable and unacceptable risk
      implicitly rests on classical liberal rather than libertarian principles; he
      justifies compulsory vaccination on the grounds that it promotes welfare. I also
      object that Brennan's argument would entail significant departures from
      libertarian institutional arrangements. This leaves libertarians with a choice:
      they can develop new arguments to demonstrate that their position is compatible
      with compulsory vaccination, or they can accept that their view entails the
      impermissibility of compulsory vaccination, and argue that this is not an
      unpalatable implication of their view.

PMID- 28432197
TI  - Colonel (Rtd) Peter Roberts.

PMID- 28432195
TI  - N-terminal Proteomics Assisted Profiling of the Unexplored Translation Initiation
      Landscape in Arabidopsis thaliana.
AB  - Proteogenomics is an emerging research field yet lacking a uniform method of
      analysis. Proteogenomic studies in which N-terminal proteomics and ribosome
      profiling are combined, suggest that a high number of protein start sites are
      currently missing in genome annotations. We constructed a proteogenomic pipeline
      specific for the analysis of N-terminal proteomics data, with the aim of
      discovering novel translational start sites outside annotated protein coding
      regions. In summary, unidentified MS/MS spectra were matched to a specific N
      terminal peptide library encompassing protein N termini encoded in the
      Arabidopsis thaliana genome. After a stringent false discovery rate filtering,
      117 protein N termini compliant with N-terminal methionine excision specificity
      and indicative of translation initiation were found. These include N-terminal
      protein extensions and translation from transposable elements and pseudogenes.
      Gene prediction provided supporting protein-coding models for approximately half
      of the protein N termini. Besides the prediction of functional domains
      (partially) contained within the newly predicted ORFs, further supporting
      evidence of translation was found in the recently released Araport11 genome re
      annotation of Arabidopsis and computational translations of sequences stored in
      public repositories. Most interestingly, complementary evidence by ribosome
      profiling was found for 23 protein N termini. Finally, by analyzing protein N
      terminal peptides, an in silico analysis demonstrates the applicability of our N
      terminal proteogenomics strategy in revealing protein-coding potential in species
      with well- and poorly-annotated genomes.

PMID- 28432198
TI  - Folate-dependent methylation of septins governs ciliogenesis during neural tube
      closure.
AB  - Periconception maternal folic acid (vitamin B9) supplementation can reduce the
      prevalence of neural tube defects (NTDs), although just how folates benefit the
      developing embryo and promote closing of the neural tube and other morphologic
      processes during development remains unknown. Folate contributes to a 1-carbon
      metabolism, which is essential for purine biosynthesis and methionine recycling
      and affects methylation of DNA, histones, and nonhistone proteins. Herein, we
      used animal models and cultured mammalian cells to demonstrate that disruption of
      the methylation pathway mediated by folate compromises normal neural tube closure
      (NTC) and ciliogenesis. We demonstrate that the embryos with NTD failed to
      adequately methylate septin2, a key regulator of cilium structure and function.
      We report that methylation of septin2 affected its GTP binding activity and
      formation of the septin2-6-7 complex. We propose that folic acid promotes normal
      NTC in some embryos by regulating the methylation of septin2, which is critical
      for normal cilium formation during early embryonic development.-Toriyama, M.,
      Toriyama, M., Wallingford, J. B., Finnell, R. H. Folate-dependent methylation of
      septins governs ciliogenesis during neural tube closure.

PMID- 28432199
TI  - Phagocytosis imprints heterogeneity in tissue-resident macrophages.
AB  - Tissue-resident macrophages display varying phenotypic and functional properties
      that are largely specified by their local environment. One of these functions,
      phagocytosis, mediates the natural disposal of billions of cells, but its
      mechanisms and consequences within living tissues are poorly defined. Using a
      parabiosis-based strategy, we identified and isolated macrophages from multiple
      tissues as they phagocytosed blood-borne cellular material. Phagocytosis was
      circadianally regulated and mediated by distinct repertoires of receptors,
      opsonins, and transcription factors in macrophages from each tissue. Although the
      tissue of residence defined the core signature of macrophages, phagocytosis
      imprinted a distinct antiinflammatory profile. Phagocytic macrophages expressed
      CD206, displayed blunted expression of Il1b, and supported tissue homeostasis.
      Thus, phagocytosis is a source of macrophage heterogeneity that acts together
      with tissue-derived factors to preserve homeostasis.

PMID- 28432201
TI  - MG53: Biological Function and Potential as a Therapeutic Target.
AB  - MG53 (also known as tripartite motif, TRIM72) is a cardiac and skeletal muscle
      specific TRIM-family protein that exhibits multiple biologic functions. First,
      MG53 participates in plasma membrane repair of the heart, skeletal muscle, and,
      other tissues. Second, MG53 is essentially involved in the cardioprotection of
      cardiac ischemic, preconditioning, and postconditioning by activating the PI3K
      Akt-GSK3beta and ERK1/2 survival signaling pathways. Moreover, systemic delivery
      of recombinant MG53 protein ameliorates the impact of a range of injury insults
      on the heart, skeletal muscle, lung, kidney, skin, and brain. It is noteworthy
      that chronic upregulation of MG53 induces insulin resistance and metabolic
      diseases, such as type 2 diabetes and its cardiovascular complications, by acting
      as an E3 ligase to mediate the degradation of insulin receptor and insulin
      receptor substrate-1. In addition, MG53 negatively regulates myogenesis. In
      summary, MG53 is a multifunctional protein involved in the vital physiologic and
      pathologic processes of multiple organs and is a promising therapeutic target for
      various human diseases. In this review, we comprehensively summarize current
      research progress on the biologic functions and therapeutic potential of MG53.

PMID- 28432202
TI  - Crossbow bolt injury: an unusual case of penetrating trauma.

PMID- 28432204
TI  - Of the people, by the people and for the people.

PMID- 28432205
TI  - Bacterial vaginosis: going full circle?

PMID- 28432200
TI  - Tissue adaptation: Implications for gut immunity and tolerance.
AB  - Tissue adaptation is an intrinsic component of immune cell development,
      influencing both resistance to pathogens and tolerance. Chronically stimulated
      surfaces of the body, in particular the gut mucosa, are the major sites where
      immune cells traffic and reside. Their adaptation to these environments requires
      constant discrimination between natural stimulation coming from harmless
      microbiota and food, and pathogens that need to be cleared. This review will
      focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized
      environment that can help us understand the plasticity of leukocytes arriving at
      various tissue sites and how tissue-related factors operate to shape immune cell
      fate and function.

PMID- 28432206
TI  - Identifying factors that lead to the persistence of imported gonorrhoeae strains:
      a modelling study.
AB  - OBJECTIVE: The importation of Neisseria gonorrhoeae (NG) strains from overseas is
      believed to be the main source of antimicrobial resistance in Australia. With
      recent sporadic cases of ceftriaxone-resistant gonorrhoea reported in Australia
      and elsewhere, we sought to model the potential for imported NG strains to
      persist in the men who have sex with men (MSM) population in Australia. METHODS:
      We developed an individual-based model to simulate the transmission of NG in a
      population of urban MSM, and used this model to investigate factors contributing
      to the probability that an imported NG strain will persist. RESULTS: The
      probability of the imported NG strain persisting as the result of a single
      importation event is less than 1%, but the probability increases to 1% if the
      imported NG strain is resistant to treatment, and further increases to 3.1% if
      the imported NG strain can also form mixed infections with the local NG strain.
      The probability of the imported NG strain persisting increases to 4.4% if there
      are at least three importation events per month within a 1-year period.
      CONCLUSION: The imported NG strain is unlikely to persist as a result of a single
      importation event. However, the probability of persistence increases if the
      imported NG strain is resistant to treatment, can form mixed infections with the
      local NG strain or there are frequent importation events. Identification of the
      factors that determine the likelihood of persistence of an imported NG strain
      could contribute to our capacity to respond appropriately and in a timely
      fashion.

PMID- 28432207
TI  - Response to imiquimod 5% cream as treatment for condyloma and anal
      intraepithelial neoplasia in HIV-positive and HIV-negative patients.

PMID- 28432208
TI  - Clinical round-up.

PMID- 28432209
TI  - A prospective, observational cohort study of the seasonal dynamics of airway
      pathogens in the aetiology of exacerbations in COPD.
AB  - BACKGROUND: The aetiology of acute exacerbations of COPD (AECOPD) is incompletely
      understood. Understanding the relationship between chronic bacterial airway
      infection and viral exposure may explain the incidence and seasonality of these
      events. METHODS: In this prospective, observational cohort study (NCT01360398),
      patients with COPD aged 40-85 years underwent sputum sampling monthly and at
      exacerbation for detection of bacteria and viruses. Results are presented for
      subjects in the full cohort, followed for 1 year. Interactions between
      exacerbation occurrence and pathogens were investigated by generalised estimating
      equation and stratified conditional logistic regression analyses. FINDINGS: The
      mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50). At
      AECOPD, the most common bacterial species were non-typeable Haemophilus
      influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was
      rhinovirus. Logistic regression analyses (culture bacterial detection) showed
      significant OR for AECOPD occurrence when M. catarrhalis was detected regardless
      of season (5.09 (95% CI 2.76 to 9.41)). When NTHi was detected, the increased
      risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to
      5.13)) than low season (OR 1.22 (0.68 to 2.22)). Bacterial and viral coinfection
      was more frequent at exacerbation (24.9%) than stable state (8.6%). A significant
      interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR
      5.18 (1.92 to 13.99); p=0.031). CONCLUSIONS: AECOPD aetiology varies with season.
      Rises in incidence in winter may be driven by increased pathogen presence as well
      as an interaction between NTHi airway infection and effects of viral infection.
      TRIAL REGISTRATION NUMBER: Results, NCT01360398.

PMID- 28432210
TI  - A randomised controlled trial of a complex intervention to reduce children's
      exposure to secondhand smoke in the home.
AB  - OBJECTIVES: Exposing children to secondhand tobacco smoke (SHS) causes
      significant harm and occurs predominantly through smoking by caregivers in the
      family home. We report a trial of a complex intervention designed to reduce
      secondhand smoke exposure of children whose primary caregiver feels unable or
      unwilling to quit smoking. DESIGN: An open-label, parallel, randomised controlled
      trial. SETTING: Deprived communities in Nottingham City and County, England
      PARTICIPANTS: Caregivers resident in Nottingham City and County in England who
      were at least 18 years old, the main caregiver of a child aged under 5 years
      living in their household, and reported that they were smoking tobacco inside
      their home. INTERVENTIONS: We compared a complex intervention combining
      personalised feedback on home air quality, behavioural support and nicotine
      replacement therapy for temporary abstinence with usual care. MAIN OUTCOMES: The
      primary outcome was change in air quality in the home, measured as average 16-24 
      hours levels of particulate matter of  < 2.5  um diameter (PM2.5), between
      baseline and 12 weeks. Secondary outcomes included changes in maximum PM2.5,
      proportion of time PM2.5 exceeded WHO recommended levels of maximum exposure of
      25  ug/mg3, child salivary cotinine, caregivers' cigarette consumption, nicotine
      dependence, determination to stop smoking, quit attempts and quitting altogether
      during the intervention. RESULTS: Arithmetic mean PM2.5 decreased significantly
      more (by 35.2 %; 95%  CI 12.7% to 51.9 %) in intervention than in usual care
      households, as did the proportion of time PM2.5 exceeded 25  ug/mg3, child
      salivary cotinine concentrations, caregivers' cigarette consumption in the home,
      nicotine dependence, determination to quit and likelihood of having made a quit
      attempt. CONCLUSIONS: By reducing exposure to SHS in the homes of children who
      live with smokers unable or unwilling to quit, this intervention offers huge
      potential to reduce children's' tobacco-related harm. TRIAL REGISTRATION NUMBER:
      ISRCTN81701383.This trial was funded by the UK National Institute for Health
      Research (NIHR): RP-PG-0608-10020.

PMID- 28432211
TI  - Recruiting and retaining youth and young adults: challenges and opportunities in
      survey research for tobacco control.
AB  - INTRODUCTION: Evaluation studies of population-based tobacco control
      interventions often rely on large-scale survey data from numerous respondents
      across many geographic areas to provide evidence of their effectiveness.
      Significant challenges for survey research have emerged with the evolving
      communications landscape, particularly for surveying hard-to-reach populations
      such as youth and young adults. This study combines the comprehensive coverage of
      an address-based sampling (ABS) frame with the timeliness of online data
      collection to develop a nationally representative longitudinal cohort of young
      people aged 15-21. METHODS: We constructed an ABS frame, partially supplemented
      with auxiliary data, to recruit this hard-to-reach sample. Branded and tested
      mail-based recruitment materials were designed to bring respondents online for
      screening, consent and surveying. Once enrolled, respondents completed online
      surveys every 6 months via computer, tablet or smartphone. Numerous strategies
      were utilized to enhance retention and representativeness RESULTS: Results detail
      sample performance, representativeness and retention rates as well as device
      utilization trends for survey completion among youth and young adult respondents.
      Panel development efforts resulted in a large, nationally representative sample
      with high retention rates. CONCLUSIONS: This study is among the first to employ
      this hybrid ABS-to-online methodology to recruit and retain youth and young
      adults in a probability-based online cohort panel. The approach is particularly
      valuable for conducting research among younger populations as it capitalizes on
      their increasing access to and comfort with digital communication. We discuss
      challenges and opportunities of panel recruitment and retention methods in an
      effort to provide valuable information for tobacco control researchers seeking to
      obtain representative, population-based samples of youth and young adults in the
      U.S. as well as across the globe.

PMID- 28432212
TI  - Into the black: Marlboro brand architecture, packaging and marketing
      communication of relative harm.

PMID- 28432213
TI  - Tobacco retail availability and risk of relapse among smokers who make a quit
      attempt: a population-based cohort study.
AB  - INTRODUCTION: The availability of tobacco is thought to influence smoking
      behaviour, but there are few longitudinal studies examining if the location and
      number of tobacco outlets has a prospective impact on smoking cessation. METHODS:
      The Ontario Tobacco Survey, a population-representative sample of Ontario adult
      smokers who were followed every 6 months for up to 3 years, was linked with
      tobacco outlet location data from the Ontario Ministry of Health. Proximity
      (distance), threshold (at least one outlet within 500 m) and density (number of
      outlets within 500 m) with respect to a smokers' home were calculated among urban
      and suburban current smokers (n=2414). Quit attempts and risk of relapse were
      assessed using logistic regression and survival analysis, adjusted for
      neighbourhood effects and individual characteristics. RESULTS: Increased density
      of tobacco outlets was associated with decreased odds of making a quit attempt
      (OR: 0.54; 95% CI 0.35 to 0.85) in high-income neighbourhoods, but not in lower
      income ones. There was an increased risk of relapse among those who had at least
      one store within 500 m (HR: 1.41 (95% CI 1.06 to 1.88). Otherwise, there was no
      association of proximity with quit attempts or relapse. CONCLUSIONS: The
      existence of a tobacco retail outlet within walking distance from home was
      associated with difficulty in succeeding in a quit attempt, while the increased
      density of stores was associated with decreased attempts in higher income
      neighbourhoods. The availability of tobacco may influence tobacco use through
      multiple mechanisms.

PMID- 28432214
TI  - A microRNA-mRNA expression network during oral siphon regeneration in Ciona.
AB  - Here we present a parallel study of mRNA and microRNA expression during oral
      siphon (OS) regeneration in Ciona robusta, and the derived network of their
      interactions. In the process of identifying 248 mRNAs and 15 microRNAs as
      differentially expressed, we also identified 57 novel microRNAs, several of which
      are among the most highly differentially expressed. Analysis of functional
      categories identified enriched transcripts related to stress responses and
      apoptosis at the wound healing stage, signaling pathways including Wnt and
      TGFbeta during early regrowth, and negative regulation of extracellular proteases
      in late stage regeneration. Consistent with the expression results, we found that
      inhibition of TGFbeta signaling blocked OS regeneration. A correlation network
      was subsequently inferred for all predicted microRNA-mRNA target pairs expressed
      during regeneration. Network-based clustering associated transcripts into 22 non
      overlapping groups, the functional analysis of which showed enrichment of stress
      response, signaling pathway and extracellular protease categories that could be
      related to specific microRNAs. Predicted targets of the miR-9 cluster suggest a
      role in regulating differentiation and the proliferative state of neural
      progenitors through regulation of the cytoskeleton and cell cycle.

PMID- 28432215
TI  - Actomyosin-based tissue folding requires a multicellular myosin gradient.
AB  - Tissue folding promotes three-dimensional (3D) form during development. In many
      cases, folding is associated with myosin accumulation at the apical surface of
      epithelial cells, as seen in the vertebrate neural tube and the Drosophila
      ventral furrow. This type of folding is characterized by constriction of apical
      cell surfaces, and the resulting cell shape change is thought to cause tissue
      folding. Here, we use quantitative microscopy to measure the pattern of
      transcription, signaling, myosin activation and cell shape in the Drosophila
      mesoderm. We found that cells within the ventral domain accumulate different
      amounts of active apical non-muscle myosin 2 depending on the distance from the
      ventral midline. This gradient in active myosin depends on a newly quantified
      gradient in upstream signaling proteins. A 3D continuum model of the embryo with
      induced contractility demonstrates that contractility gradients, but not
      contractility per se, promote changes to surface curvature and folding. As
      predicted by the model, experimental broadening of the myosin domain in vivo
      disrupts tissue curvature where myosin is uniform. Our data argue that apical
      contractility gradients are important for tissue folding.

PMID- 28432217
TI  - RARbeta2 is required for vertebrate somitogenesis.
AB  - During vertebrate somitogenesis, retinoic acid is known to establish the position
      of the determination wavefront, controlling where new somites are permitted to
      form along the anteroposterior body axis. Less is understood about how RAR
      regulates somite patterning, rostral-caudal boundary setting, specialization of
      myotome subdivisions or the specific RAR subtype that is required for somite
      patterning. Characterizing the function of RARbeta has been challenging due to
      the absence of embryonic phenotypes in murine loss-of-function studies. Using the
      Xenopus system, we show that RARbeta2 plays a specific role in somite number and
      size, restriction of the presomitic mesoderm anterior border, somite chevron
      morphology and hypaxial myoblast migration. Rarbeta2 is the RAR subtype whose
      expression is most upregulated in response to ligand and its localization in the
      trunk somites positions it at the right time and place to respond to embryonic
      retinoid levels during somitogenesis. RARbeta2 positively regulates Tbx3 a marker
      of hypaxial muscle, and negatively regulates Tbx6 via Ripply2 to restrict the
      anterior boundaries of the presomitic mesoderm and caudal progenitor pool. These
      results demonstrate for the first time an early and essential role for RARbeta2
      in vertebrate somitogenesis.

PMID- 28432216
TI  - Embryonic cholecystitis and defective gallbladder contraction in the Sox17
      haploinsufficient mouse model of biliary atresia.
AB  - The gallbladder excretes cytotoxic bile acids into the duodenum through the
      cystic duct and common bile duct system. Sox17 haploinsufficiency causes biliary
      atresia-like phenotypes and hepatitis in late organogenesis mouse embryos, but
      the molecular and cellular mechanisms underlying this remain unclear. In this
      study, transcriptomic analyses revealed the early onset of cholecystitis in
      Sox17+/- embryos, together with the appearance of ectopic cystic duct-like
      epithelia in their gallbladders. The embryonic hepatitis showed positive
      correlations with the severity of cholecystitis in individual Sox17+/- embryos.
      Embryonic hepatitis could be induced by conditional deletion of Sox17 in the
      primordial gallbladder epithelia but not in fetal liver hepatoblasts. The Sox17+/
      gallbladder also showed a drastic reduction in sonic hedgehog expression,
      leading to aberrant smooth muscle formation and defective contraction of the
      fetal gallbladder. The defective gallbladder contraction positively correlated
      with the severity of embryonic hepatitis in Sox17+/- embryos, suggesting a
      potential contribution of embryonic cholecystitis and fetal gallbladder
      contraction in the early pathogenesis of congenital biliary atresia.

PMID- 28432219
TI  - Optimized CUBIC protocol for three-dimensional imaging of chicken embryos at
      single-cell resolution.
AB  - The CUBIC tissue-clearing protocol has been optimized to produce translucent
      immunostained whole chicken embryos and embryo brains. When combined with
      multispectral light-sheet microscopy, the validated protocol presented here
      provides a rapid, inexpensive and reliable method for acquiring accurate
      histological images that preserve three-dimensional structural relationships with
      single-cell resolution in whole early-stage chicken embryos and in the whole
      brains of late-stage embryos.

PMID- 28432218
TI  - Dynamics of growth zone patterning in the milkweed bug Oncopeltus fasciatus.
AB  - We describe the dynamic process of abdominal segment generation in the milkweed
      bug Oncopeltus fasciatus We present detailed morphological measurements of the
      growing germband throughout segmentation. Our data are complemented by cell
      division profiles and expression patterns of key genes, including invected and
      even-skipped as markers for different stages of segment formation. We describe
      morphological and mechanistic changes in the growth zone and in nascent segments
      during the generation of individual segments and throughout segmentation, and
      examine the relative contribution of newly formed versus existing tissue to
      segment formation. Although abdominal segment addition is primarily generated
      through the rearrangement of a pool of undifferentiated cells, there is
      nonetheless proliferation in the posterior. By correlating proliferation with
      gene expression in the growth zone, we propose a model for growth zone dynamics
      during segmentation in which the growth zone is functionally subdivided into two
      distinct regions: a posterior region devoted to a slow rate of growth among
      undifferentiated cells, and an anterior region in which segmental differentiation
      is initiated and proliferation inhibited.

PMID- 28432221
TI  - Biological considerations of plasma-derived and recombinant factor VIII
      immunogenicity.
AB  - In hemophilia A, the most severe complication of factor VIII (FVIII) replacement
      therapy involves the formation of FVIII neutralizing antibodies, also known as
      inhibitors, in 25% to 30% of patients. This adverse event is associated with a
      significant increase in morbidity and economic burden, thus highlighting the need
      to identify methods to limit FVIII immunogenicity. Inhibitor development is
      regulated by a complex balance of genetic factors, such as FVIII genotype, and
      environmental variables, such as coexistent inflammation. One of the hypothesized
      risk factors of inhibitor development is the source of the FVIII concentrate,
      which could be either recombinant or plasma derived. Differential immunogenicity
      of these concentrates has been documented in several recent epidemiologic
      studies, thus generating significant debate within the hemophilia treatment
      community. To date, these discussions have been unable to reach a consensus
      regarding how these outcomes might be integrated into enhancing clinical care.
      Moreover, the biological mechanistic explanations for the observed differences
      are poorly understood. In this article, we complement the existing epidemiologic
      investigations with an overview of the range of possible biochemical and
      immunologic mechanisms that may contribute to the different immune outcomes
      observed with plasma-derived and recombinant FVIII products.

PMID- 28432220
TI  - miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition
      of the interferon response.
AB  - FLT3-ITD+ acute myeloid leukemia (AML) accounts for ~25% of all AML cases and is
      a subtype that carries a poor prognosis. microRNA-155 (miR-155) is specifically
      overexpressed in FLT3-ITD+ AML compared with FLT3 wild-type (FLT3-WT) AML and is
      critical for the growth of FLT3-ITD+ AML cells in vitro. However, miR-155's role
      in regulating FLT3-ITD-mediated disease in vivo remains unclear. In this study,
      we used a genetic mouse model to determine whether miR-155 influences the
      development of FLT3-ITD-induced myeloproliferative disease. Results indicate that
      miR-155 promotes FLT3-ITD-induced myeloid expansion in the bone marrow, spleen,
      and peripheral blood. Mechanistically, miR-155 increases proliferation of the
      hematopoietic stem and progenitor cell compartments by reducing the growth
      inhibitory effects of the interferon (IFN) response, and this involves targeting
      of Cebpb. Consistent with our observations in mice, primary FLT3-ITD+ AML
      clinical samples have significantly higher miR-155 levels and a lower IFN
      response compared with FLT3-WT AML samples. Further, inhibition of miR-155 in
      FLT3-ITD+ AML cell lines using CRISPR/Cas9, or primary FLT3-ITD+ AML samples
      using locked nucleic acid antisense inhibitors, results in an elevated IFN
      response and reduces colony formation. Altogether, our data reveal that miR-155
      collaborates with FLT3-ITD to promote myeloid cell expansion in vivo and that
      this involves a multitarget mechanism that includes repression of IFN signaling.

PMID- 28432222
TI  - Low expression of hexokinase-2 is associated with false-negative FDG-positron
      emission tomography in multiple myeloma.
AB  - 18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) and diffusion
      weighted magnetic resonance imaging with background signal suppression (DWIBS)
      are 2 powerful functional imaging modalities in the evaluation of malignant
      plasma cell (PC) disease multiple myeloma (MM). Preliminary observations have
      suggested that MM patients with extensive disease according to DWIBS may be
      reported as being disease-free on FDG-PET ("PET false-negative"). The aim of this
      study was to describe the proportion of PET false-negativity in a representative
      set of 227 newly diagnosed MM patients with simultaneous assessment of FDG-PET
      and DWIBS, and to identify tumor-intrinsic features associated with this pattern.
      We found the incidence of PET false-negativity to be 11%. Neither tumor load
      associated parameters, such as degree of bone marrow PC infiltration, nor the PC
      proliferation rate were associated with this subset. However, the gene coding for
      hexokinase-2, which catalyzes the first step of glycolysis, was significantly
      lower expressed in PET false-negative cases (5.3-fold change, P < .001) which
      provides a mechanistic explanation for this feature. In conclusion, we
      demonstrate a relevant number of patients with FDG-PET false-negative MM and a
      strong association between hexokinase-2 expression and this negativity: a finding
      which may also be relevant for clinical imaging of other hematological cancers.

PMID- 28432223
TI  - FLI1 level during megakaryopoiesis affects thrombopoiesis and platelet biology.
AB  - Friend leukemia virus integration 1 (FLI1), a critical transcription factor (TF)
      during megakaryocyte differentiation, is among genes hemizygously deleted in
      Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau
      syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed
      to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)
      derived megakaryocytes (iMegs) to better understand these clinical disorders,
      beginning with iPSCs generated from a patient with PTSx and iPSCs from a control
      line with a targeted heterozygous FLI1 knockout (FLI1+/-). PTSx and FLI1+/- iMegs
      replicate many of the described megakaryocyte/platelet features, including a
      decrease in iMeg yield and fewer platelets released per iMeg. Platelets released
      in vivo from infusion of these iMegs had poor half-lives and functionality. We
      noted that the closely linked E26 transformation-specific proto-oncogene 1 (ETS1)
      is overexpressed in these FLI1-deficient iMegs, suggesting FLI1 negatively
      regulates ETS1 in megakaryopoiesis. Finally, we examined whether FLI1
      overexpression would affect megakaryopoiesis and thrombopoiesis. We found
      increased yield of noninjured, in vitro iMeg yield and increased in vivo yield,
      half-life, and functionality of released platelets. These studies confirm FLI1
      heterozygosity results in pleiotropic defects similar to those noted with other
      critical megakaryocyte-specific TFs; however, unlike those TFs, FLI1
      overexpression improved yield and functionality.

PMID- 28432225
TI  - Chemo Heart.

PMID- 28432224
TI  - A Bacterial Cause of Cancer: An Historical Essay.
AB  - This article reviews the history of the discovery of microbes that increase the
      risk of cancer of some tissues with a special emphasis on the bacterium
      Helicobacter pylori and the role played by two Australian physicians, neither
      schooled in research, who had open minds about the shibboleth that mycobacteria
      (acid-fast organisms) can survive the acid environment of the stomach, but that
      other pathogenic bacteria cannot. They discovered one of the most important human
      pathogens, Helicobacter pylori, and showed it capable of inducing severe gastric
      inflammatory disease. Subsequently, others built on their observations and showed
      it capable of inducing two gastric neoplasms: carcinoma and lymphoma. The
      Oncologist 2017;22:542-548.

PMID- 28432229
TI  - 50 years on - time for a fresh look at the Veterinary Surgeons Act?

PMID- 28432233
TI  - Using motivational interviewing can help vets change client behaviour.

PMID- 28432246
TI  - Celebrating veterinary excellence.

PMID- 28432226
TI  - Everolimus Plus Exemestane in Advanced Breast Cancer: Safety Results of the
      BALLET Study on Patients Previously Treated Without and with Chemotherapy in the
      Metastatic Setting.
AB  - BACKGROUND: The BALLET study was an open-label, multicenter, expanded access
      study designed to allow treatment with everolimus plus exemestane in
      postmenopausal women with hormone receptor-positive metastatic breast cancer
      progressed following prior endocrine therapy. A post hoc analysis to evaluate if
      previous chemotherapy in the metastatic setting affects the safety profile of the
      combination regimen of everolimus and exemestane was conducted on the Italian
      subset, as it represented the major part of the patients enrolled (54%). PATIENTS
      AND METHODS: One thousand one hundred and fifty-one Italian patients were
      included in the present post hoc analysis, which focused on two sets of patients:
      patients who never received chemotherapy in the metastatic setting (36.1%) and
      patients who received at least one chemotherapy treatment in the metastatic
      setting (63.9%). RESULTS: One thousand one hundred and sixteen patients (97.0%)
      prematurely discontinued the study drug, and the main reasons reported were
      disease progression (39.1%), local reimbursement of everolimus (31.1%), and
      adverse events (AEs) (16.1%). The median duration of study treatment exposure was
      139.5 days for exemestane and 135.0 days for everolimus. At least one AE was
      experienced by 92.5% of patients. The incidence of everolimus-related AEs was
      higher (83.9%) when compared with those that occurred with exemestane (29.1%),
      and the most commonly reported everolimus-related AE was stomatitis (51.3%).
      However, no significant difference in terms of safety related to the combination
      occurred between patients without and with chemotherapy in the metastatic
      setting. CONCLUSION: Real-life data of the Italian patients BALLET-related cohort
      were an adequate setting to state that previous chemotherapy did not affect the
      safety profile of the combination regimen of everolimus and exemestane.
      IMPLICATIONS FOR PRACTICE: With the advent of new targeted agents for advanced or
      metastatic breast cancer, multiple lines of therapy may be possible, and
      components of the combined regimens can overlap from one line to another. Thus,
      it is important to assess even the potential of cumulative and additive toxic
      effects among the drugs. Previous chemotherapy did not affect the safety profile
      of the combination regimen of everolimus and exemestane. The continuous
      monitoring of the safety signals of this drug combination from general clinical
      practice is important, in particular for stomatitis.

PMID- 28432247
TI  - Do we need to explain the occurrence of atypical scrapie?

PMID- 28432249
TI  - Further evidence of leprosy in Isle of Wight red squirrels.

PMID- 28432250
TI  - Treating peripheral vestibular disease-associated nausea.

PMID- 28432251
TI  - Election of trustees to the Vetlife Board.

PMID- 28432252
TI  - Career-long support that starts with new graduates.
AB  - Armed with the knowledge that newly qualified vets want a clinical mentor and
      surgical support in their first job, Independent Vetcare set up its two-year
      Graduate Academy. Operations manager Darren Mackintosh describes how it works.

PMID- 28432253
TI  - Ten-minute chat.
AB  - Melissa Kelson is a fourth year student at the Royal Veterinary College. She
      recently spent a week of her EMS with the BVA's journals.

PMID- 28432254
TI  - TLR4-defective (C3H/HeJ) mice are not protected from cast immobilization-induced
      muscle atrophy.
AB  - Recent studies have shown that activation of Toll-like receptor (TLR)4 signaling
      may be an important factor in muscle atrophy and excessive inflammatory response
      associated with immobilization. To examine the role of TLR4 signaling on cast
      immobilization-induced skeletal muscle atrophy, we tested the hypothesis that
      muscle atrophy and inflammation after cast immobilization is reduced in TLR4
      defective mice. TLR4-defective (C3H/HeJ) and wild type (C3H/HeN) mice were
      divided into control and cast-immobilization groups. Cast immobilization was
      imposed for 14 days. Cast immobilization increased TLR4 mRNA expression in the
      gastrocnemius and decreased muscle mass and cross-sectional area (CSA) of the
      gastrocnemius fibers. However, there was no difference in the gastrocnemius
      muscle mass and CSA between TLR4-defective and wild type mice. Cast
      immobilization-induced increase in ubiquitin E3 ligases (MAFbx/Atrogin-1 and
      MuRF1), inflammatory cytokines, and macrophage/monocyte marker mRNAs were
      unaffected by defective TLR4. Our findings in C3H/HeJ mice suggested that TLR4
      signaling might not play an essential role in immobilization-induced muscle
      atrophy.

PMID- 28432255
TI  - Osmotic activation of a Ca2+-dependent phospholipase C pathway that regulates ?N
      TRPV1-mediated currents in rat supraoptic neurons.
AB  - The magnocellular neurosecretory cells (MNCs) of the hypothalamus regulate body
      fluid balance by releasing the hormones vasopressin (VP) and oxytocin (OT) in an
      osmolality-dependent manner. Elevations of external osmolality increase MNC
      firing and hormone release. MNC osmosensitivity is largely due to activation of a
      mechanosensitive non-selective cation current that responds to osmotically-evoked
      changes in MNC volume and is mediated by an N-terminal variant of the TRPV1
      channel (?N TRPV1). We report a novel mechanism by which increases in osmolality
      may modulate ?N TRPV1-mediated currents and thus influence MNC electrical
      behaviour. We showed previously that acute elevations of external osmolality
      activate the enzyme phospholipase C (PLC) in isolated MNCs. We now show that the
      osmotic activation of PLC has a time course and dose-dependence that is
      consistent with a role in MNC osmosensitivity and that it contributes to the
      osmotically-evoked increase in non-selective cation current in MNCs through a
      protein kinase C-dependent pathway. We furthermore show that the mechanism of
      osmotic activation of PLC requires an increase in internal Ca2+ that depends on
      influx through L-type Ca2+ channels. Our data therefore suggest that MNCs possess
      an osmotically-activated Ca2+-dependent PLC that contributes to the osmotic
      activation of ?N TRPV1 and may therefore be important in MNC osmosensitivity and
      in central osmoregulation.

PMID- 28432256
TI  - Global Sensitivity Analysis of OnGuard Models Identifies Key Hubs for Transport
      Interaction in Stomatal Dynamics.
AB  - The physical requirement for charge to balance across biological membranes means
      that the transmembrane transport of each ionic species is interrelated, and
      manipulating solute flux through any one transporter will affect other
      transporters at the same membrane, often with unforeseen consequences. The
      OnGuard systems modeling platform has helped to resolve the mechanics of stomatal
      movements, uncovering previously unexpected behaviors of stomata. To date,
      however, the manual approach to exploring model parameter space has captured
      little formal information about the emergent connections between parameters that
      define the most interesting properties of the system as a whole. Here, we
      introduce global sensitivity analysis to identify interacting parameters
      affecting a number of outputs commonly accessed in experiments in Arabidopsis
      (Arabidopsis thaliana). The analysis highlights synergies between transporters
      affecting the balance between Ca2+ sequestration and Ca2+ release pathways,
      notably those associated with internal Ca2+ stores and their turnover. Other,
      unexpected synergies appear, including with the plasma membrane anion channels
      and H+-ATPase and with the tonoplast TPK K+ channel. These emergent synergies,
      and the core hubs of interaction that they define, identify subsets of
      transporters associated with free cytosolic Ca2+ concentration that represent key
      targets to enhance plant performance in the future. They also highlight the
      importance of interactions between the voltage regulation of the plasma membrane
      and tonoplast in coordinating transport between the different cellular
      compartments.

PMID- 28432257
TI  - Excess Diffuse Light Absorption in Upper Mesophyll Limits CO2 Drawdown and
      Depresses Photosynthesis.
AB  - In agricultural and natural systems, diffuse light can enhance plant primary
      productivity due to deeper penetration into and greater irradiance of the entire
      canopy. However, for individual sun-grown leaves from three species,
      photosynthesis is actually less efficient under diffuse compared with direct
      light. Despite its potential impact on canopy-level productivity, the mechanism
      for this leaf-level diffuse light photosynthetic depression effect is unknown.
      Here, we investigate if the spatial distribution of light absorption relative to
      electron transport capacity in sun- and shade-grown sunflower (Helianthus annuus)
      leaves underlies its previously observed diffuse light photosynthetic depression.
      Using a new one-dimensional porous medium finite element gas-exchange model
      parameterized with light absorption profiles, we found that weaker penetration of
      diffuse versus direct light into the mesophyll of sun-grown sunflower leaves led
      to a more heterogenous saturation of electron transport capacity and lowered its
      CO2 concentration drawdown capacity in the intercellular airspace and chloroplast
      stroma. This decoupling of light availability from photosynthetic capacity under
      diffuse light is sufficient to generate an 11% decline in photosynthesis in sun
      grown but not shade-grown leaves, primarily because thin shade-grown leaves
      similarly distribute diffuse and direct light throughout the mesophyll. Finally,
      we illustrate how diffuse light photosynthetic depression could overcome
      enhancement in canopies with low light extinction coefficients and/or leaf area,
      pointing toward a novel direction for future research.

PMID- 28432258
TI  - LIL3, a Light-Harvesting Complex Protein, Links Terpenoid and Tetrapyrrole
      Biosynthesis in Arabidopsis thaliana.
AB  - The LIL3 protein of Arabidopsis (Arabidopsis thaliana) belongs to the light
      harvesting complex (LHC) protein family, which also includes the light-harvesting
      chlorophyll-binding proteins of photosystems I and II, the early-light-inducible
      proteins, PsbS involved in nonphotochemical quenching, and the one-helix proteins
      and their cyanobacterial homologs designated high-light-inducible proteins. Each
      member of this family is characterized by one or two LHC transmembrane domains
      (referred to as the LHC motif) to which potential functions such as chlorophyll
      binding, protein interaction, and integration of interacting partners into the
      plastid membranes have been attributed. Initially, LIL3 was shown to interact
      with geranylgeranyl reductase (CHLP), an enzyme of terpene biosynthesis that
      supplies the hydrocarbon chain for chlorophyll and tocopherol. Here, we show
      another function of LIL3 for the stability of protochlorophyllide oxidoreductase
      (POR). Multiple protein-protein interaction analyses suggest the direct physical
      interaction of LIL3 with POR but not with chlorophyll synthase. Consistently,
      LIL3-deficient plants exhibit substantial loss of POR as well as CHLP, which is
      not due to defective transcription of the POR and CHLP genes but to the
      posttranslational modification of their protein products. Interestingly, in vitro
      biochemical analyses provide novel evidence that LIL3 shows high binding affinity
      to protochlorophyllide, the substrate of POR. Taken together, this study suggests
      a critical role for LIL3 in the organization of later steps in chlorophyll
      biosynthesis. We suggest that LIL3 associates with POR and CHLP and thus
      contributes to the supply of the two metabolites, chlorophyllide and phytyl
      pyrophosphate, required for the final step in chlorophyll a synthesis.

PMID- 28432259
TI  - Probing native metal ion association sites through quenching of fluorophores in
      the nucleotide-binding domains of the ABC transporter MsbA.
AB  - ATP-binding cassette (ABC) transporters are ubiquitously present in prokaryotic
      and eukaryotic cells. Binding of ATP to the nucleotide-binding domains (NBDs)
      elicits major conformational changes of the transporters resulting in the
      transport of the substrate across the membrane. The availability of a crystal
      structure of the NBDs enabled us to elucidate the local structure and small-scale
      dynamics in the NBDs. Here, we labeled the ABC transporter MsbA, a homodimeric
      flippase from Escherichia coli, with a fluorescent probe, Alexa532, within the
      NBDs. ATP application elicited collisional quenching, whereas no quenching was
      observed after the addition of ATP analogs or ATP hydrolysis inhibitors. The
      Alexa532-conjugated MsbA variants exhibited transition metal ion Forster
      resonance energy transfer (tmFRET) after the addition of Ni2+, and ATP decreased
      this Ni2+-mediated FRET of the NBDs. Structure modeling developed from
      crystallographic data and examination of tmFRET measurements of MsbA variants in
      the absence of ATP revealed the presence of metal ion-associated pockets (MiAPs)
      in the NBDs. Three histidines were predicted to participate in chelating Ni2+ in
      the two possible MiAPs. Performing histidine-substitution experiments with the
      NBDs showed that the dissociation constant for Ni2+ of MiAP2 was smaller than
      that of MiAP1. The structural allocation of the MiAPs was further supported by
      showing that the addition of Cu2+ resulted in higher quenching than Ni2+ Taken
      together, the present study showed that the NBDs contain two native binding sites
      for metal ions and ATP addition affects the Ni2+-binding activity of the MiAPs.

PMID- 28432260
TI  - Dual histone reader ZMYND8 inhibits cancer cell invasion by positively regulating
      epithelial genes.
AB  - Enhanced migratory potential and invasiveness of cancer cells contribute
      crucially to cancer progression. These phenotypes are achieved by precise
      alteration of invasion-associated genes through local epigenetic modifications
      which are recognized by a class of proteins termed a chromatin reader. ZMYND8
      [zinc finger MYND (myeloid, Nervy and DEAF-1)-type containing 8], a key component
      of the transcription regulatory network, has recently been shown to be a novel
      reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis
      upon silencing this chromatin reader, we identified a subset of genes involved in
      cell proliferation and invasion/migration regulated by ZMYND8. Detailed analysis
      uncovered its antiproliferative activity through BrdU incorporation, alteration
      in the expression of proliferation markers, and cell cycle regulating genes and
      cell viability assays. In addition, performing wound healing and
      invasion/migration assays, its anti-invasive nature is evident. Interestingly,
      epithelial-mesenchymal transition (EMT), a key mechanism of cellular invasion, is
      regulated by ZMYND8 where we identified its selective enrichment on promoters of
      CLDN1/CDH1 genes, rich in H3K36Me2/H4K16Ac marks, leading to their up-regulation.
      Thus, the presence of ZMYND8 could be implicated in maintaining the epithelial
      phenotype of cells. Furthermore, syngeneic mice, injected with ZMYND8
      overexpressed invasive breast cancer cells, showed reduction in tumor volume and
      weight. In concert with this, we observed a significant down-regulation of ZMYND8
      in invasive ductal and lobular breast cancer tissues compared with normal tissue.
      Taken together, our study elucidates a novel function of ZMYND8 in regulating EMT
      and invasion of cancer cells, possibly through its chromatin reader function.

PMID- 28432261
TI  - CCM2 and PAK4 act downstream of atrial natriuretic peptide signaling to promote
      cell spreading.
AB  - Atrial natriuretic peptide (ANP) is a cardiac hormone released by the atrium in
      response to stretching forces. Via its receptor, guanylyl cyclase-A (GC-A), ANP
      maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and
      hypotensive effects mediated, in part, by endothelial cells. Both in vivo and in
      vitro, ANP enhances endothelial barrier function by reducing RhoA activity and
      reorganizing the actin cytoskeleton. We established mouse endothelial cells that
      stably express GC-A and used them to analyze the molecular mechanisms responsible
      for actin reorganization. Stimulation by ANP resulted in phosphorylation of
      myosin light chain (MLC) and promotion of cell spreading. p21-activated kinase 4
      (PAK4) and cerebral cavernous malformations 2 (CCM2), a scaffold protein involved
      in a cerebrovascular disease, were required for the phosphorylation of MLC and
      promotion of cell spreading by ANP. Finally, in addition to the GC domain, the
      kinase homology domain of GC-A was also required for ANP/GC-A signaling. Our
      results indicate that CCM2 and PAK4 are important downstream mediators of ANP/GC
      A signaling involved in cell spreading, an important initial step in the
      enhancement of endothelial barrier function.

PMID- 28432262
TI  - Quantitative Imaging of Cerebral Thromboemboli In Vivo: The Effects of Tissue
      Type Plasminogen Activator.
AB  - BACKGROUND AND PURPOSE: Quantitative imaging for the noninvasive assessment of
      thrombolysis is needed to advance basic and clinical thrombosis-related research
      and tailor tissue-type plasminogen activator (tPA) treatment for stroke patients.
      We quantified the evolution of cerebral thromboemboli using fibrin-targeted
      glycol chitosan-coated gold nanoparticles and microcomputed tomography,
      with/without tPA therapy. METHODS: We injected thrombi into the distal internal
      carotid artery in mice (n=50). Fifty-five minutes later, we injected fibrin
      targeted glycol chitosan-coated gold nanoparticles, and 5 minutes after that, we
      treated animals with tPA or not (25 mg/kg). We acquired serial microcomputed
      tomography images for 24 hours posttreatment. RESULTS: Thrombus burden at
      baseline was 784*103+/-59*103 MUm2 for the tPA group (n=42) and 655*103+/-103*103
      MUm2 for the saline group (n=8; P=0.37). Thrombus shrinkage began at 0.5 to 1
      hour after tPA therapy, with a maximum initial rate of change at 4603+/-957
      MUm2/min. The rate of change lowered to ~61% level of the initial in hours 1 to
      2, followed by ~29% and ~1% in hours 2 to 3 and 3 to 24, respectively. Thus, 85%
      of total thrombolysis over 24 hours (~500 MUm2, equivalent to 64% of the baseline
      thrombus burden) occurred within the first 3 hours of treatment. Thrombus burden
      at 24 hours could be predicted at around 1.5 to 2 hours. Saline treatment was not
      associated with significant changes in the thrombus burden. Infarct size was
      smaller in the tPA group versus saline group (18.1+/-2.3 versus 45.8+/-3.3 mm2;
      P<0.01). Infarct size correlated to final thrombus burden (r=0.71; P<0.01). Time
      to thrombolysis, completeness of thrombolysis, and tPA therapy were independent
      predictors of infarct size. CONCLUSIONS: Thromboembolic burden and the efficacy
      of tPA therapy can be assessed serially, noninvasively, and quantitatively using
      high-resolution microcomputed tomography and a fibrin-binding nanoparticle
      imaging agent.

PMID- 28432263
TI  - Intracranial Dural Arteriovenous Fistulae.

PMID- 28432264
TI  - Prediction of Stroke Subtype and Recanalization Using Susceptibility Vessel Sign
      on Susceptibility-Weighted Magnetic Resonance Imaging.
AB  - BACKGROUND AND PURPOSE: The susceptibility vessel sign (SVS) is a hypointense
      signal visualized because of the susceptibility effect of thrombi, sensitively
      detected on susceptibility-weighted magnetic resonance imaging. The relationship
      of SVS parameters with the stroke subtype and recanalization status after
      endovascular treatment remains uncertain. METHODS: The data from 89 patients with
      acute stroke caused by anterior circulation infarcts who underwent susceptibility
      weighted magnetic resonance imaging before endovascular treatment were examined.
      Independent reviewers, blinded to the stroke subtype and recanalization status,
      measured the SVS diameter, length, and estimated volume. The intra- and
      interrater agreements of the SVS parameters were assessed. RESULTS: The SVS was
      identified in 78% of the patients. SVS was more commonly associated with
      cardioembolism than with noncardioembolism (P=0.01). The SVS diameter (P<0.01)
      and length (P=0.01) were larger in the cardioembolism group. The SVS diameter was
      larger in the recanalization group (thrombolysis in cerebral infarction >=2b)
      than in the nonrecanalization group (P=0.04). Multivariable analysis revealed
      that the SVS diameter was an independent predictor of cardioembolism (adjusted
      odds ratio, 1.97; 95% confidence interval, 1.34-2.90; P<0.01). There was no
      significant association between the SVS volume and the recanalization status
      (adjusted odds ratio, 1.003; 95% confidence interval, 0.999-1.006; P=0.12). The
      optimal cutoff value of the SVS diameter for the cardioembolism was 5.5 mm
      (sensitivity, 45.6%; specificity, 93.8%). CONCLUSIONS: Increased SVS diameter on
      susceptibility-weighted magnetic resonance imaging may predict cardioembolism. No
      clear association was found between SVS volume and endovascular recanalization.

PMID- 28432265
TI  - ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double
      Blind Actovegin): A Randomized Controlled Trial to Assess the Efficacy of
      Actovegin in Poststroke Cognitive Impairment.
AB  - BACKGROUND AND PURPOSE: Poststroke cognitive impairment is a debilitating
      consequence of stroke. The aim of this study was to assess whether Actovegin
      confers cognitive benefit in patients who have had an ischemic stroke. METHODS:
      This was a 12-month, parallel-group, randomized, multicenter, double-blind,
      placebo-controlled study. Eligible patients were >=60 years of age with a
      Montreal Cognitive Assessment test score of <=25 points. Patients were randomized
      into 2 groups within 1 week of acute supratentorial ischemic stroke in a 1:1
      ratio: Actovegin (a deproteinized hemoderivative of calf blood, 2000 mg/d for
      <=20 intravenous infusions followed by 1200 mg/d orally) or placebo for 6 months.
      Patients were treated in accordance with standard clinical practice for a further
      6 months. The primary end point was the change from baseline in Alzheimer's
      Disease Assessment Scale, cognitive subscale, extended version at 6 months.
      RESULTS: Two-hundred forty-eight patients were randomized to Actovegin and 255
      patients to placebo. At month 6, the least squares mean change from baseline in
      Alzheimer's Disease Assessment Scale, cognitive subscale, extended version was 
      6.8 for Actovegin and -4.6 for placebo; the estimated treatment difference was 
      2.3 (95% confidence interval, -3.9, -0.7; P=0.005). Recurrent ischemic stroke was
      the most frequently reported serious adverse event, with a nonsignificantly
      higher number for Actovegin versus placebo. CONCLUSIONS: Actovegin had a
      beneficial effect on cognitive outcomes in patients with poststroke cognitive
      impairment. The safety experience was consistent with the known safety and
      tolerability profile of the drug. These results warrant confirmation in
      additional robustly designed studies. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01582854.

PMID- 28432266
TI  - Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial
      Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular
      Treatment of Acute Ischemic Stroke in the Netherlands).
AB  - BACKGROUND AND PURPOSE: High blood pressure (BP) is associated with poor outcome
      and the occurrence of symptomatic intracranial hemorrhage in acute ischemic
      stroke. Whether BP influences the benefit or safety of intra-arterial treatment
      (IAT) is not known. We aimed to assess the relation of BP with functional
      outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT.
      METHODS: This is a post hoc analysis of the MR CLEAN (Multicenter Randomized
      Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the
      Netherlands). BP was measured at baseline, before IAT or stroke unit admission.
      We estimated the association of baseline BP with the score on the modified Rankin
      Scale at 90 days and safety parameters with ordinal and logistic regression
      analysis. Effect of BP on the effect of IAT was tested with multiplicative
      interaction terms. RESULTS: Systolic BP (SBP) had the best correlation with
      functional outcome. This correlation was U-shaped; both low and high baseline SBP
      were associated with poor functional outcome. Higher SBP was associated with
      symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg
      higher SBP [95% confidence interval, 1.09-1.44]). Between SBP and IAT, there was
      no interaction for functional outcome, symptomatic intracranial hemorrhage, or
      other safety parameters; the absolute benefit of IAT was evident for the whole
      SBP range. The same was found for diastolic BP. CONCLUSIONS: BP does not affect
      the benefit or safety of IAT in patients with acute ischemic stroke caused by
      proximal intracranial vessel occlusion. Our data provide no arguments to withhold
      or delay IAT based on BP. CLINICAL TRIAL REGISTRATION: URL:
      http://www.isrctn.com. Unique identifier: ISRCTN10888758.

PMID- 28432267
TI  - Assessment of lung function in a large cohort of patients with acromegaly.
AB  - OBJECTIVE: Acromegaly is associated with increased mortality due to respiratory
      disease. To date, lung function in patients with acromegaly has only been
      assessed in small studies, with contradicting results. We assessed lung function
      parameters in a large cohort of patients with acromegaly. DESIGN: Lung function
      of acromegaly patients was prospectively assessed using spirometry, blood gas
      analysis and body plethysmography. Biochemical indicators of acromegaly were
      assessed through measurement of growth hormone and IGF-I levels. This study was
      performed at the endocrinology outpatient clinic of a tertiary referral center in
      Germany. METHODS: We prospectively tested lung function of 109 acromegaly
      patients (53 male, 56 female; aged 24-82 years; 80 with active acromegaly)
      without severe acute or chronic pulmonary disease. We compared lung volume, air
      flow, airway resistance and blood gases to normative data. RESULTS: Acromegaly
      patients had greater lung volumes (maximal vital capacity, intra-thoracic gas
      volume and residual volume: P < 0.001, total lung capacity: P = 0.006) and showed
      signs of small airway obstruction (reduced maximum expiratory flow when 75% of
      the forced vital capacity (FVC) has been exhaled: P < 0.001, lesser peak
      expiratory flow: P = 0.01). There was no significant difference between active
      and inactive acromegaly. Female patients had significantly altered lung function
      in terms of subclinical airway obstruction. CONCLUSIONS: In our cross-sectional
      analysis of lung function in 109 patients with acromegaly, lung volumes were
      increased compared to healthy controls. Additionally, female patients showed
      signs of subclinical airway obstruction. There was no difference between patients
      with active acromegaly compared with patients biochemically in remission.

PMID- 28432268
TI  - Clinical outcomes after delayed thyroid surgery in patients with papillary
      thyroid microcarcinoma.
AB  - OBJECTIVE: Active surveillance is an option for patients with papillary thyroid
      microcarcinoma (PTMC). However, the long-term clinical outcomes after delayed
      surgery remain unclear. We compared the long-term clinical outcomes of PTMC
      patients according to the time interval between initial diagnosis and surgery.
      DESIGN AND METHODS: In this individual risk factor-matched cohort study, PTMC
      patients were classified into three groups according to the delay period: <=6
      months, 6-12 months and >12 months. Patients were matched by age, sex, extent of
      surgery, initial tumor size as measured by ultrasonography (US), and by the
      presence of extrathyroidal extension, multifocal tumors and central cervical
      lymph node metastasis. We compared the dynamic risk stratification (DRS) and the
      development of structural persistent/recurrent disease of patients. RESULTS: A
      total of 2863 patients were assigned to three groups. Their mean age was 50
      years, 81% were female and 66% underwent lobectomy. The mean tumor size at the
      initial US was 0.63 cm. There were no significant differences in
      clinicopathological characteristics between groups after individual risk factor
      matching. Comparison of the DRS revealed no significant difference according to
      the delay period (P = 0.07). During the median 4.8 years of follow-up, there were
      no significant differences in the development of structural recurrent/persistent
      disease (P = 0.34) and disease-free survival (P = 0.25) between groups.
      CONCLUSIONS: In PTMC patients, delayed surgery was not associated with higher
      risk of structural recurrent/persistent disease compared to immediate surgery.
      These findings support the notion that surgical treatment can be safely delayed
      in patients with PTMC under close monitoring.

PMID- 28432269
TI  - Altered sleep patterns in patients with non-functional GHRH receptor.
AB  - OBJECTIVES: GH-releasing hormone (GHRH) exerts hypnotic actions increasing the
      non-rapid eye movement (NREM) sleep. Conversely, GH stimulates the REM sleep. GH
      deficiency (GHD) often leads to sleep problems, daytime fatigue and reduced
      quality of life (QoL). GHD may be due to lack of hypothalamic GHRH or destruction
      of somatotroph cells. We have described a cohort with isolated GHD (IGHD) due to
      GHRH resistance caused by a homozygous null mutation (c.57 + 1G > A) in the GHRH
      receptor gene. They have normal QoL and no obvious complaints of chronic
      tiredness. The aim of this study was to determine the sleep quality in these
      subjects. METHODS: A cross-sectional study was carried out in 21 adult IGHD
      subjects, and 21 age- and gender-matched controls. Objective sleep assessment
      included polygraphic records of the awake, stages NREM [N1 (drowsiness), N2 and
      N3 (already sleeping)] and REM (R). Subjective evaluation included the Pittsburgh
      Sleep Quality Index, the Insomnia Severity Index and the Epworth Sleepiness
      Scale. RESULTS: IGHD subjects showed a reduction in sleep efficiency (P = 0.007),
      total sleep time (P = 0.028), duration of N2 and R in minutes (P = 0.026 and P =
      0.046 respectively), but had increased duration and percentage of N1 stage (P =
      0.029 and P = 0.022 respectively), wake (P = 0.007) and wake-time after sleep
      onset (P = 0.017). There was no difference in N3 or in sleep quality
      questionnaire scores. CONCLUSION: Patients with IGHD due to GHRH resistance
      exhibit objective reduction in the sleep quality, with changes in NREM and REM
      sleep, with no detectable subjective consequences. GHRH resistance seems to have
      a preponderant role over GHD in the sleep quality of these subjects.

PMID- 28432270
TI  - Discriminating between virilizing ovary tumors and ovary hyperthecosis in
      postmenopausal women: clinical data, hormonal profiles and image studies.
AB  - BACKGROUND: The presence of virilizing signs associated with high serum androgen
      levels in postmenopausal women is rare. Virilizing ovarian tumors (VOTs) and
      ovarian stromal hyperthecosis (OH) are the most common etiologies in virilized
      postmenopausal women. The differential diagnosis between these two conditions is
      often difficult. OBJECTIVE: To evaluate the contribution of clinical features,
      hormonal profiles and radiological studies to the differential diagnosis of VOT
      and OH. DESIGN: A retrospective study. SETTING: A tertiary center. MAIN OUTCOME
      MEASURES: Clinical data, hormonal status (T, E2, LH and FSH), pelvic images
      (transvaginal sonography and MRI) and anatomopathology were reviewed. PATIENTS:
      Thirty-four postmenopausal women with a diagnosis of VOT (13 women) and OH (21
      women) were evaluated retrospectively. RESULTS: Clinical signs of
      hyperandrogenism were more prevalent in the VOT group than the OH group. Although
      the VOT group showed higher T and E2 levels and lower gonadotropin levels than
      the OH group, a great overlap occurred among the hormone levels. A pelvic MRI
      provided an accurate differentiation of these two conditions. CONCLUSION: In this
      group of patients, the main features contributing to the differential diagnosis
      of VOT and OH were serum levels of testosterone and gonadotropins and the
      presence of an ovarian nodule identified on the MRI. Although the association of
      clinical, hormonal and radiological features contributes to the differential
      diagnosis of these two conditions, histopathological analysis remains the gold
      standard for the diagnosis of ovarian hyperandrogenism in postmenopausal women.

PMID- 28432271
TI  - Knockdown of PRDX2 sensitizes colon cancer cells to 5-FU by suppressing the
      PI3K/AKT signaling pathway.
AB  - Although, 5-Fluorouracil (5-FU) remains widely used in adjuvant therapy in
      patients with colon cancer, resistance to 5-FU-based chemotherapy is an important
      reason for treatment failure. Recent studies have reported that an enhanced
      reactive oxygen species (ROS) scavenging system shows drug resistance to 5-FU.
      Peroxiredoxin-2 (PRDX2), is an important member of the ROS scavenging system, and
      may be a potential target that promotes chemosensitivity to 5-FU in colon cancer.
      Here, we depleted PRDX2 by PRDX2-shRNA-LV transduction in two colon cancer cell
      lines and found that in vitro PRDX2 knockdown facilitates cell death, and
      apoptosis in 5-FU-treated colon cancer cells. In addition, we found that PRDX2
      depletion in mice treated with 5-FU resulted in, inhibition of tumor growth,
      compared with mice treated with 5-FU alone. Our data also suggested that the
      PI3K/AKT signaling pathway links PRDX2 with 5-FU-induced apoptosis in colon
      cancer. Furthermore, when PRDX2 was overexpressed in colon cancer cells, we found
      increased p-AKT protein expression and reduced Bcl-2/Bax protein expression.
      PRDX2 and p-AKT protein expression were analyzed by immunohistochemistry
      technology in human colon carcinoma tissues. Pearson correlation coefficient is
      0.873 and P<0.05. PRDX2 depletion led to reduced p-AKT expression and PI3K/AKT
      pathway inhibition promoted cell apoptosis in HT29 cell line. Taken together, our
      study suggests that decreasing the expression of PRDX2 could be a promising
      strategy for increasing the sensitivity of colon cancer cells to 5-FU.

PMID- 28432273
TI  - miR-509-3-5P inhibits the invasion and lymphatic metastasis by targeting PODXL
      and serves as a novel prognostic indicator for gastric cancer.
AB  - BACKGROUND: Our study aimed to investigate the clinicopathological feature and
      prognostic role of miR-509-3-5P in gastric cancer, to determine the invasive and
      metastatic role of miR-509-3-5P in vitro and in vivo and to explore the molecular
      mechanism between miR-509-3-5P and PODXL. RESULTS: Strikingly lower miR-509-3-5P
      expression was detected in gastric cancer tissues with advanced tumor stage, poor
      differentiation and advanced pT stage, and was regarded as an independent
      prognostic role for poor prognosis. MiR-509-3-5P expression was markedly down
      regulated in gastric cancer cell lines and tissues comparing with normal gastric
      cell and adjacent normal tissues, respectively. Decreased expression of miR-509-3
      5P promoted the colony, migration and invasion abilities of gastric cancer cells
      in vitro as well as tumorigenesis and lymph node metastasis in vivo. Based on the
      luciferase assay and tissue microarray, PODXL was regarded as a target gene of
      miR-509-3-5P. MATERIALS AND METHODS: The expression of miR-509-3-5P in gastric
      cancer patients and its clinicopathological relationships as well as prognostic
      role was studied employing tissue microarray; qRT-PCR was applied to explore miR
      509-3-5P expression in gastric cancer cell lines and samples. Moreover, public
      database was used to analyze the expression of miR-509-3-5P and PODXL. Functional
      and molecular mechanism experiments were performed in vitro and in vivo.
      CONCLUSIONS: Overexpression of miR-509-3-5P inhibits the invasion and metastasis
      of gastric cancer in vitro and in vivo, functioning as a tumor suppressor, by
      targeting PODXL. More importantly, miR-509-3-5P was downregulated in gastric
      cancer tissues and may serve as a novel prognostic indicator for gastric cancer.

PMID- 28432272
TI  - Establishment of an in vitro culture model of theca cells from hierarchical
      follicles in ducks.
AB  - Theca cells, including theca interna cells and theca externa cells, are vital
      components of ovarian follicles. The aim of the present study is to identify a
      reliable method for the in vitro culture of theca cells from duck ovarian
      hierarchical (F4-F2) follicles. We improved the method for cell separation by
      using trypsin to further remove granular cells, and we increased the
      concentration of fetal bovine serum used in in vitro culture to improve
      cytoactivity. Cell antibody immunofluorescence (IF) showed that all inoculated
      cells could be stained by the CYP17A1/19A1 antibody but not by the FSHR antibody,
      which could stain granulosa cells. Furthermore, morphological differences were
      observed between the outlines of theca interna and externa cells and in their
      nuclei. Growth curve and CYP17A1/19A1 mRNA relative expression analyses suggested
      that the growth profile of theca interna cells may have been significantly
      different from that of theca externa cells in vitro Theca interna cells
      experienced the logarithmic phase on d1-d2, the plateau phase on d2-d3, and the
      senescence phase after d3, while theca externa cells experienced the logarithmic
      phase on d1-d3, the plateau phase on d3-d5, and the senescence phase after d5.
      Taken together, these results suggested that we have successfully established a
      reliable theca cell culture model and further defined theca cell characteristics
      in vitro.

PMID- 28432274
TI  - Sensitive detection of viable circulating tumor cells using a novel conditionally
      telomerase-selective replicating adenovirus in non-small cell lung cancer
      patients.
AB  - Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of
      cancer patients. Detection of non-small cell lung cancer (NSCLC) using an
      antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has
      low sensitivity; the loss of epithelial markers leads to underestimation of CTCs
      with mesenchymal phenotype. We propose a new approach for detection of viable
      CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs),
      using the new telomerase-specific replication-selective adenovirus (OBP-1101),
      TelomeScan F35. Peripheral venous blood samples and clinicopathological data were
      collected from 123 NSCLC patients. The sensitivity of CTC detection was 69.1%,
      and for patients with stage I, II, III and IV, it was 59.6%, 40.0%, 85.7%, and
      75.0%, respectively. Among the EMT-CTC samples, 46% were vimentin positive and
      39.0% of non-EMT-CTC samples were EpCAM positive. Patients testing positive for
      EMT-CTCs at baseline had poor response to chemotherapy (P = 0.025) and decreased
      progression-free survival (EMT-CTC positive vs. negative: 193 +/- 47 days vs. 388
      +/- 47. days, P = 0.040) in comparison to those testing negative. TelomeScan F35
      is a highly sensitive CTC detection system and will be a useful screening tool
      for early diagnosis of NSCLC patients. Mesenchymal-phenotype CTCs are crucial
      indicators of chemotherapeutic efficacy in NSCLC patients.

PMID- 28432275
TI  - Better cancer specific survival in young small cell lung cancer patients
      especially with AJCC stage III.
AB  - It has been reported that younger patients with non-small cell lung cancer
      (NSCLC) tend to have a better prognosis. Yet, few studies have focused on the
      clinicopathological characteristics and prognosis of young small cell lung cancer
      (SCLC), especially for patients with age < 50. In our study, we used
      Surveillance, Epidemiology, and End Results (SEER) population-based data and
      identified 16503 patients with SCLC including 711 patients aged < 50, 3338
      patients aged 50-59, 5937 patients aged 60-69, 4649 patients aged 70-79 and 1868
      patients aged >= 80 between 2010 and 2013. The Kaplan-Meier methods was used to
      develop the survival curve, and the results showed that the SCLC patients with
      aged < 50 tended to a better over survival (OS) and cancer specific survival
      (CSS) (all, P < 0.001). In addition, Cox regression model was used to analyze
      survival prognosis factors and perform subgroup analysis. The results showed that
      age was an independent prognostic factor for CSS (P < 0.001). Importantly, we
      found that for the patients with AJCC stage III subgroup, the age < 50 had
      apparent CSS benefit compared with any other age group (all, P < 0.01).
      Interestingly, for the patients with no surgery, radiation and no radiation
      subgroup, the age < 50 had no apparent CSS benefit only compared with age 50-59
      (all, P > 0.05). In conclusion, our study demonstrated that the SCLC patients
      with aged < 50 tended had a better survival benefit, especially for patients with
      AJCC stage III.

PMID- 28432276
TI  - Identification of common immunodominant antigens of Eimeria tenella, Eimeria
      acervulina and Eimeria maxima by immunoproteomic analysis.
AB  - Clinical chicken coccidiosis is mostly caused by simultaneous infection of
      several Eimeria species, and host immunity against Eimeria is species-specific.
      It is urgent to identify common immunodominant antigen of Eimeria for developing
      multivalent anticoccidial vaccines. In this study, sporozoite proteins of Eimeria
      tenella, Eimeria acervulina and Eimeria maxima were analyzed by two-dimensional
      electrophoresis (2DE). Western bot analysis was performed on the yielded 2DE gel
      using antisera of E. tenella E. acervulina and E. maxima respectively. Next, the
      detected immunodominant spots were identified by comparing the data from MALDI
      TOF-MS/MS with available databases. Finally, Eimeria common antigens were
      identified by comparing amino acid sequence between the three Eimeria species.
      The results showed that analysis by 2DE of sporozoite proteins detected 629, 626
      and 632 protein spots from E. tenella, E. acervulina and E. maxima respectively.
      Western bot analysis revealed 50 (E. tenella), 64 (E. acervulina) and 57 (E.
      maxima) immunodominant spots from the sporozoite 2DE gels of the three Eimeria
      species. The immunodominant spots were identified as 33, 27 and 25 immunodominant
      antigens of E. tenella, E. acervulina and E. maxima respectively. Fifty-four
      immunodominant proteins were identified as 18 ortholog proteins among the three
      Eimeria species. Finally, 5 of the 18 ortholog proteins were identified as common
      immunodominant antigens including elongation factor 2 (EF-2), 14-3-3 protein,
      ubiquitin-conjugating enzyme domain-containing protein (UCE) and glyceraldehyde-3
      phosphate dehydrogenase (GAPDH). In conclusion, our results not only provide
      Eimeria sporozoite immunodominant antigen map and additional immunodominant
      antigens, but also common immunodominant antigens for developing multivalent
      anticoccidial vaccines.

PMID- 28432277
TI  - Transforming growth factor beta1 promotes invasion of human JEG-3 trophoblast
      cells via TGF-beta/Smad3 signaling pathway.
AB  - Transforming growth factor (TGF)-beta1 is involved invasion of human
      trophoblasts. However, the underlying mechanisms remain unclear. In this study,
      we performed Transwell assay and found that TGF-beta1 promoted the invasion of
      trophoblast cell line JEG-3. Treatment with TGF-beta1 up-regulated the expression
      of receptor-regulated Smad transcription factors Smad2 and Smad3, and two
      invasive-associated genes, namely, matrix metallopeptidase (MMP)-9 and MMP-2, in
      JEG-3 cells. Over-expressing activin receptor-like kinase (ALK) 5, the TGF-beta
      type I receptor (TbetaRI) enhanced the up-regulation of Smad2, Smad3, MMP-9, and
      MMP-2 induced by TGF-beta1, whereas application of TbetaRI inhibitor SB431542
      diminished the stimulatory effects of TGF-beta1 on these genes. Furthermore,
      transfection of Smad3 and ALK-5 seperately or in combination into JEG-3 cells
      before TGF-beta1 treatment significantly increased the expression of MMP-9 and
      MMP-2. By contrast, silencing Smad3 and Smad2 by siRNAs significantly decreased
      the expression of MMP-9 and MMP-2, with Smad3 silence having a more potent
      inhibitory effect. Inhibiting TbetaRI with SB431542 or knockdown of Smad3, but
      not Smad2, abolished the stimulatory effect of TGF-beta1 on the invasion of JEG-3
      cells. Taken together, the results indicate that TGF-beta1 activates the Smads
      signaling pathway in JEG-3 trophoblast cells and Smad3 play a key role in TGF
      beta1-induced invasion of JEG-3 and up-regulation of MMP-9 and MMP-2 expression.

PMID- 28432278
TI  - Blood glucose concentration and risk of liver cancer: systematic review and meta
      analysis of prospective studies.
AB  - The question of whether elevated blood glucose is a risk factor for liver cancer
      has been intensively studied, yet with inconsistent results. To explore the
      relationship between blood glucose concentration and risk of liver cancer, we
      conduct a meta-analysis of prospective studies. Literature search was
      comprehensively performed using database of PubMed, EMBASE and the Cochrane
      Library through October 2016. Random-effect models were used to combine the
      effect estimations. Eight articles containing ten studies with a total of 1975
      liver cancer cases were included. The pooled RRs demonstrated that elevated
      fasting blood glucose was associated with increased risk of liver cancer
      (combined RRs: 1.77; 95% CI: 1.46, 2.13) with mild heterogeneity (I2 = 30.40%, P
      = 0.17). In sensitivity analysis, the pooled result remained significant
      (combined RRs: 1.33; 95% CI: 1.12, 1.59; I2 = 33.90%, P = 0.16) when we
      restricted blood glucose categories in the range of nondiabetic subjects. We also
      detected a J-shaped non-linear dose-response relationship between blood glucose
      concentration and risk of liver cancer. There is evidence that elevated blood
      glucose increases risk of liver cancer across the range of prediabetes and
      diabetes. Considering the rapidly increasing prevalence of prediabetes and
      diabetes, controlling blood glucose may lower the risk of liver cancer.

PMID- 28432279
TI  - IL-35 induces N2 phenotype of neutrophils to promote tumor growth.
AB  - IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells,
      B cells, macrophages and dendritic cells. Neutrophils are important innate immune
      cells that play key roles in tumor development. The effect of IL-35 on
      neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil
      polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and
      promote neutrophil infiltration into tumor microenvironment. The sustained
      expression of IL-35 could promote chronic inflammation to augment the
      proangiogenic and immunosuppressive function of neutrophils. IL-35 stimulated
      macrophages to secrete proinflammatory cytokines IL-1beta and IL-6. IL-1beta
      stimulated gammadelta T cells to produce IL-17, which in turn increased the
      production of G-CSF. By increasing the expression of G-CSF and IL-6, IL-35 could
      up-regulate the expression of MMP-9 and Bv8, and down-regulate TRAIL expression
      in neutrophils, thus augmenting the proangiogenic function of neutrophils.
      Moreover, G-CSF/IL-6 induced the enhanced activation of STAT3 and ERK pathways in
      neutrophils, thus increasing the expression of iNOS to suppress T cell
      activation. Our findings suggest that IL-35 can promote tumor progression by
      functioning as an up-stream cytokine to promote cancer-associated inflammation
      and control neutrophil polarization. Targeting IL-35 might be an important
      approach for designing new strategy of tumor therapy.

PMID- 28432280
TI  - Small molecules targeting histone demethylase genes (KDMs) inhibit growth of
      temozolomide-resistant glioblastoma cells.
AB  - In glioblastoma several histone demethylase genes (KDM) are overexpressed
      compared to normal brain tissue and the development of Temozolomide (TMZ)
      resistance is accompanied by the transient further increased expression of KDM5A
      and other KDMs following a mechanism that we defined as "epigenetic resilience".
      We hypothesized that targeting KDMs may kill the cells that survive the cytotoxic
      therapy.We determined the effect of JIB 04 and CPI-455, two KDM inhibitors, on
      glioblastoma cells and found that both molecules are more effective against TMZ
      resistant rather than native cells.Because of its lower IC50, we focused on JIB
      04 that targets KDM5A and other KDMs as well. We have shown that this molecule
      activates autophagic and apoptotic pathways, interferes with cell cycle
      progression, inhibits cell clonogenicity and dephosphorylates Akt thus
      inactivating a potent pro-survival pathway. We performed combination
      temozolomide/JIB 04 in vitro treatments showing that these two molecules, under
      certain conditions, have a strong synergic effect and we hypothesize that JIB 04
      intercepts the cells that escape the G2 block exerted by TMZ. Finally we studied
      the permeability of JIB 04 across the blood-brain barrier and found that this
      molecule reaches bioactive concentration in the brain; furthermore a pilot in
      vivo experiment in an orthotopic GB xenograft model showed a trend toward longer
      survival in treated mice with an Hazard Ratio of 0.5.In conclusion we propose
      that the combination between cytotoxic drugs and molecules acting on the
      epigenetic landscape may offer the opportunity to develop new therapies for this
      invariably lethal disease.

PMID- 28432281
TI  - The role of non-thermal atmospheric pressure biocompatible plasma in the
      differentiation of osteoblastic precursor cells, MC3T3-E1.
AB  - Non-thermal atmospheric pressure plasma is ionized matter, composed of highly
      reactive species that include positive ions, negative ions, free radicals,
      neutral atoms, and molecules. Recent reports have suggested that non-thermal
      biocompatible plasma (NBP) can selectively kill a variety of cancer cells, and
      promote stem cell differentiation. However as of yet, the regulation of
      proliferation and differentiation potential of NBP has been poorly
      understood.Here, we investigated the effects of NBP on the osteogenic
      differentiation of precursor cell lines of osteoblasts, MC3T3 E1 and SaOS-2. For
      in vitro osteogenic differentiation, precursor cell lines were treated with NBP,
      and cultured with osteogenic induction medium. After 10 days of treatment, the
      NBP was shown to be effective in osteogenic differentiation in MC3T3 E1 cells by
      von Kossa and Alizarin Red S staining assay. Real-time PCR was then performed to
      investigate the expression of osteogenic specific genes, Runx2, OCN, COL1, ALP
      and osterix in MC3T3 E1 cells after treatment with NBP for 4 days. Furthermore,
      analysis of the protein expression showed that NBP treatment significantly
      reduced PI3K/AKT signaling and MAPK family signaling. However, p38 controlled
      phosphorylation of transcription factor forkhead box O1 (FoxO1) that related to
      cell differentiation with increased phosphorylated p38. These results suggest
      that non-thermal atmospheric pressure plasma can induce osteogenic
      differentiation, and enhance bone formation.

PMID- 28432283
TI  - Efficacy and Safety of Single-Balloon Versus Double-Balloon Enteroscopy: A Single
      Center Retrospective Analysis.
AB  - BACKGROUND Single-balloon endoscopy (SBE) has been introduced as a simplified
      endoscopy technique after the promotion of double-balloon endoscopy (DBE). The
      difference in clinical performance between DBE and SBE is still not very clear.
      In this study, we aimed to compare the efficacy and safety between these 2
      endoscopic procedures. MATERIAL AND METHODS A total of 173 patients with
      suspected small bowel disease were enrolled into this study from January 2007 to
      December 2011. All cases were divided into DBE or SBE groups according to the
      endoscopic procedures they underwent. We then compared the diagnostic yield, the
      influence of DBE and SBE on the diagnostic/therapeutic course, the examination
      time, and post-procedure discomfort between DBE and SBE groups. RESULTS We
      observed no notable adverse events during or after the examinations.
      Additionally, SBE displays a significantly higher diagnostic rate (62.0%) than
      DBE (35.6%) via the anal approach (P=0.0137), while there was no difference in
      positive diagnostic rate between DBE and SBE via the oral route. Remarkably, it
      takes significantly less time to perform SBE examinations (38.86+/-5.64 minutes)
      than DBE procedures (41.80+/-6.50 minutes) via the oral route (P=0.048), although
      the average examination time for DBE is close to that for SBE via the anal route
      (P=0.952). However, DBE and SBE are similar in terms of their impact on the
      diagnostic/therapeutic course and complication rate. CONCLUSIONS Both SBE and DBE
      are very safe procedures to perform and SBE is a preferred choice for the
      evaluation of small bowel diseases in terms of diagnostic rate via the anal route
      compared with DBE.

PMID- 28432282
TI  - Loss-of-function myostatin mutation increases insulin sensitivity and browning of
      white fat in Meishan pigs.
AB  - Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with
      a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear
      if the inhibition of myostatin could be used as an approach to treat human
      obesity and insulin resistance. In this study, we investigated if the inhibition
      of porcine myostatin has any effect on fat deposition and insulin sensitivity
      using genetically engineered Meishan pigs containing a myostatin loss-of-function
      mutation (Mstn -/- ). Our results indicated that, when compared with wild-type
      pigs, the amount of subcutaneous fat and leaf fat of Mstn -/- pigs were
      significantly decreased mainly due to the browning of subcutaneous adipose
      tissue. Additionally, the serum insulin level decreased and the insulin
      sensitivity increased significantly in Mstn -/- pigs. Moreover, we found a
      significant increase in levels of insulin receptor and insulin receptor substrate
      proteins in skeletal muscle of Mstn -/- pigs, which then activating the insulin
      signaling pathway. Irisin-mediated regulation is not the only pathway for the
      activation of insulin signal in Mstn -/- skeletal muscle. This study provides
      valuable insight for the treatment of human obesity and diabetes mellitus.

PMID- 28432284
TI  - Treatment with Recombinant Factor XIII (Tretten) in a Pregnant Woman with Factor
      XIII Deficiency.
AB  - BACKGROUND Factor XIII deficiency is associated with recurrent miscarriages in
      women. CASE REPORT In this report, we present a patient with factor XIII
      deficiency and some comorbidities who had had previous miscarriages. She began
      treatment with factor XIII subunit A (XIII-A) replacement treatment Recombinant
      factor XIII (Tretten) at a dose of 2500 units monthly and was able, for the first
      time, to carry a pregnancy almost to term. Although she experienced some
      obstetrical complications, she delivered a healthy baby. To the best of our
      knowledge, this is the first report of the use of Tretten during pregnancy.
      CONCLUSIONS Tretten, which is not indicated in pregnancy, offered a safe,
      effective treatment for miscarriages secondary to factor XIII-A deficiency in our
      patient. Further research is required to confirm this finding.

PMID- 28432285
TI  - NOD1 modulates IL-10 signalling in human dendritic cells.
AB  - NOD1 belongs to the family of NOD-like receptors, which is a group of well
      characterised, cytosolic pattern-recognition receptors. The best-studied function
      of NOD-like receptors is their role in generating immediate pro-inflammatory and
      antimicrobial responses by detecting specific bacterial peptidoglycans or by
      responding to cellular stress and danger-associated molecules. The present study
      describes a regulatory, peptidoglycan-independent function of NOD1 in anti
      inflammatory immune responses. We report that, in human dendritic cells, NOD1
      balances IL-10-induced STAT1 and STAT3 activation by a SOCS2-dependent mechanism,
      thereby suppressing the tolerogenic dendritic cell phenotype. Based on these
      findings, we propose that NOD1 contributes to inflammation not only by promoting
      pro-inflammatory processes, but also by suppressing anti-inflammatory pathways.

PMID- 28432286
TI  - The Breathing, Thinking, Functioning clinical model: a proposal to facilitate
      evidence-based breathlessness management in chronic respiratory disease.
AB  - Refractory breathlessness is a highly prevalent and distressing symptom in
      advanced chronic respiratory disease. Its intensity is not reliably predicted by
      the severity of lung pathology, with unhelpful emotions and behaviours
      inadvertently exacerbating and perpetuating the problem. Improved symptom
      management is possible if clinicians choose appropriate non-pharmacological
      approaches, but these require engagement and commitment from both patients and
      clinicians. The Breathing Thinking Functioning clinical model is a proposal,
      developed from current evidence, that has the potential to facilitate effective
      symptom control, by providing a rationale and focus for treatment.

PMID- 28432287
TI  - Advantages of Unfair Quantum Ground-State Sampling.
AB  - The debate around the potential superiority of quantum annealers over their
      classical counterparts has been ongoing since the inception of the field. Recent
      technological breakthroughs, which have led to the manufacture of experimental
      prototypes of quantum annealing optimizers with sizes approaching the practical
      regime, have reignited this discussion. However, the demonstration of quantum
      annealing speedups remains to this day an elusive albeit coveted goal. We examine
      the power of quantum annealers to provide a different type of quantum enhancement
      of practical relevance, namely, their ability to serve as useful samplers from
      the ground-state manifolds of combinatorial optimization problems. We study, both
      numerically by simulating stoquastic and non-stoquastic quantum annealing
      processes, and experimentally, using a prototypical quantum annealing processor,
      the ability of quantum annealers to sample the ground-states of spin glasses
      differently than thermal samplers. We demonstrate that (i) quantum annealers
      sample the ground-state manifolds of spin glasses very differently than thermal
      optimizers (ii) the nature of the quantum fluctuations driving the annealing
      process has a decisive effect on the final distribution, and (iii) the
      experimental quantum annealer samples ground-state manifolds significantly
      differently than thermal and ideal quantum annealers. We illustrate how quantum
      annealers may serve as powerful tools when complementing standard sampling
      algorithms.

PMID- 28432288
TI  - Overexpression of human NR2B receptor subunit in LMAN causes stuttering and song
      sequence changes in adult zebra finches.
AB  - Zebra finches (Taeniopygia guttata) learn to produce songs in a manner
      reminiscent of spoken language development in humans. One candidate gene
      implicated in influencing learning is the N-methyl-D-aspartate (NMDA) subtype 2B
      glutamate receptor (NR2B). Consistent with this idea, NR2B levels are high in the
      song learning nucleus LMAN (lateral magnocellular nucleus of the anterior
      nidopallium) during juvenile vocal learning, and decreases to low levels in
      adults after learning is complete and the song becomes more stereotyped. To test
      for the role of NR2B in generating song plasticity, we manipulated NR2B
      expression in LMAN of adult male zebra finches by increasing its protein levels
      to those found in juvenile birds, using a lentivirus containing the full-length
      coding sequence of the human NR2B subunit. We found that increased NR2B
      expression in adult LMAN induced increases in song sequence diversity and slower
      song tempo more similar to juvenile songs, but also increased syllable
      repetitions similar to stuttering. We did not observe these effects in control
      birds with overexpression of NR2B outside of LMAN or with the green fluorescent
      protein (GFP) in LMAN. Our results suggest that low NR2B subunit expression in
      adult LMAN is important in conserving features of stereotyped adult courtship
      song.

PMID- 28432289
TI  - Simultaneous Detection of EGFR and VEGF in Colorectal Cancer using Fluorescence
      Raman Endoscopy.
AB  - Fluorescence endomicroscopy provides quick access to molecular targets, while
      Raman spectroscopy allows the detection of multiple molecular targets. Using a
      simultaneous fluorescence-Raman endoscopic system (FRES), we herein demonstrate
      its potential in cancer diagnosis in an orthotopically induced colorectal cancer
      (CRC) xenograft model. In the model, epidermal growth factor receptor (EGFR) and
      vascular endothelial growth factor (VEGF) were targeted with antibody-conjugated
      fluorescence and surface-enhanced Raman scattering (F-SERS) dots. FRES
      demonstrated fast signal detection and multiplex targeting ability using
      fluorescence and Raman signals to detect the F-SERS dots. In addition, FRES
      showed a multiplex targeting ability even on a subcentimeter-sized CRC after
      spraying with a dose of 50 ug F-SERS dots. In conclusion, molecular
      characteristics of tumor cells (EGFR in cancer cell membranes) and tumor
      microenvironments (VEGF in the extracellular matrix) could be simultaneously
      investigated when performing a colonoscopy.

PMID- 28432290
TI  - A tongue for all seasons: extreme phenotypic flexibility in salamandrid newts.
AB  - Many organisms faced with seasonally fluctuating abiotic and biotic conditions
      respond by altering their phenotype to account for the demands of environmental
      changes. Here we discovered that newts, which switch seasonally between an
      aquatic and terrestrial lifestyle, grow a complex adhesive system on their tongue
      pad consisting of slender lingual papillae and mucus-producing cells to increase
      the efficiency of prey capture as they move from water onto land. The adhesive
      system is reduced again as newts switch back to their aquatic stage, where they
      use suction to capture prey. As suction performance is also enhanced seasonally
      by reshaping of the mouth due to the growth of labial lobes, our results show
      that newts are exceptional in exhibiting phenotypic flexibility in two
      alternating components (i.e. tongue pad and labial lobes) within a single
      functional system, and suggest that this form of phenotypic flexibility demands
      complex genetic regulation.

PMID- 28432291
TI  - Birth weight changes in a major city under rapid socioeconomic transition in
      China.
AB  - Estimates of trends in birth weight may be useful in evaluating population
      health. We aimed to determine whether temporal changes in birth weight have
      occurred amongst 2.3 million neonates born in Guangzhou, China, during 2001-2015
      and investigate the socioeconomic determinants of any changes. Trends in mean
      birth weight and annualized changes with the associated 95% confidence intervals
      (CIs) in the incidence of small for gestational age (SGA) and large for
      gestational age (LGA), defined as birth weight <10th or >90th centile
      respectively for gestational age and sex, were examined using linear and Poisson
      regression models. We found that mean birth weight declined by 1.07 grams/year
      from 2001 to 2015. After adjustment for gestational length, the decline in birth
      weight was attenuated (0.37 grams/year). The incidence of both SGA and LGA
      significantly decreased during the study period (annual decrease of 1.6% [95% CI,
      1.5% to 1.7%] for SGA, 1.6% [95% CI, 1.5% to 1.8%] for LGA). We found a narrowing
      of disparities in SGA and LGA incidence across different maternal educational
      levels and residence location. Our results demonstrate that there has been an
      increase in the proportion of neonates born in the healthy birth weight range in
      Guangzhou.

PMID- 28432292
TI  - Created mangrove wetlands store belowground carbon and surface elevation change
      enables them to adjust to sea-level rise.
AB  - Mangrove wetlands provide ecosystem services for millions of people, most
      prominently by providing storm protection, food and fodder. Mangrove wetlands are
      also valuable ecosystems for promoting carbon (C) sequestration and storage.
      However, loss of mangrove wetlands and these ecosystem services are a global
      concern, prompting the restoration and creation of mangrove wetlands as a
      potential solution. Here, we investigate soil surface elevation change, and its
      components, in created mangrove wetlands over a 25 year developmental gradient.
      All created mangrove wetlands were exceeding current relative sea-level rise
      rates (2.6 mm yr-1), with surface elevation change of 4.2-11.0 mm yr-1 compared
      with 1.5-7.2 mm yr-1 for nearby reference mangroves. While mangrove wetlands
      store C persistently in roots/soils, storage capacity is most valuable if
      maintained with future sea-level rise. Through empirical modeling, we discovered
      that properly designed creation projects may not only yield enhanced C storage,
      but also can facilitate wetland persistence perennially under current rates of
      sea-level rise and, for most sites, for over a century with projected medium
      accelerations in sea-level rise (IPCC RCP 6.0). Only the fastest projected
      accelerations in sea-level rise (IPCC RCP 8.5) led to widespread submergence and
      potential loss of stored C for created mangrove wetlands before 2100.

PMID- 28432293
TI  - Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and
      hypoxia to activate Runx1.
AB  - The adult mammalian central nervous system (CNS) contains a population of slowly
      dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply
      new oligodendrocytes throughout the life of animal. While adult OPCs develop from
      rapidly dividing perinatal OPCs, the mechanisms underlying their quiescence
      remain unknown. Here, we show that perinatal rodent OPCs cultured with thyroid
      hormone (TH) under hypoxia become quiescent and acquire adult OPCs-like
      characteristics. The cyclin-dependent kinase inhibitor p15/INK4b plays crucial
      roles in the TH-dependent cell cycle deceleration in OPCs under hypoxia. Klf9 is
      a direct target of TH-dependent signaling. Under hypoxic conditions, hypoxia
      inducible factors mediates runt-related transcription factor 1 activity to induce
      G1 arrest in OPCs through enhancing TH-dependent p15/INK4b expression. As adult
      OPCs display phenotypes of adult somatic stem cells in the CNS, the current
      results shed light on environmental requirements for the quiescence of adult
      somatic stem cells during their development from actively proliferating
      stem/progenitor cells.

PMID- 28432294
TI  - Genome-wide identification, characterization of the MADS-box gene family in
      Chinese jujube and their involvement in flower development.
AB  - MADS-box genes encode transcription factors that are involved in plant
      development control (particularly in floral organogenesis) and signal
      transduction pathways, though a comprehensive analysis of MADS-box family
      proteins in Chinese jujube (Ziziphus jujuba Mill.) is still missing. Here, we
      report a genome-wide analysis of the MADS-box gene family in Chinese jujube.
      Based on phylogenetic analyses, 52 jujube MADS-box genes were classified into 25
      MIKCC-type, 3 MIKC*-type, 16 Malpha, 5 Mbeta and 3 Mgamma genes. 37 genes were
      randomly distributed across all 12 putative chromosomes. We found that the type
      II genes are more complex than the type I genes and that tandem duplications have
      occurred in three groups of MADS-box genes. Meanwhile, some gene pairs in the
      same clade displayed similar or distinct expression profiles, suggesting possible
      functional redundancy or divergence. MIKCC-type genes exhibited typical temporal
      and spatial expression patterns in the four whorls of floral tissues. The
      expressions of B, C/D and E-type genes were significantly suppressed in phyllody
      as compared to flower, providing valuable evidence for their involvement in
      flower development. This study is the first comprehensive analysis of the MADS
      box family in jujube, and provides valuable information for elucidating molecular
      regulation mechanism of jujube flower development.

PMID- 28432295
TI  - Laparoscopic Versus Open Liver Resection for Colorectal Liver Metastases: A
      Comprehensive Systematic Review and Meta-analysis.
AB  - The effects of laparoscopic liver resection (LLR) and open liver resection (OLR)
      on oncological outcomes for colorectal cancer liver metastases (CCLM) remain
      inconclusive. Major databases were searched from January 1992 to October 2016.
      Effects of LLR vs OLR were determined. The primary endpoints were oncological
      outcomes. In total, 32 eligible non-randomized studies with 4697 patients (LLR:
      1809, OLR: 2888) were analyzed. There were higher rates of clear surgical margins
      (OR: 1.64, 95%CI: 1.32 to 2.05, p < 0.00001) in the LLR group, without
      significant differences in disease recurrence, 3- or 5-year overall survival(OS)
      and disease free survival(DFS) between the two approaches. LLR was associated
      with less intraoperative blood loss (WMD: -147.46 [-195.78 to -99.15] mL, P <
      0.00001) and fewer blood transfusions (OR: 0.41 [0.30-0.58], P < 0.00001), but
      with longer operation time (WMD:14.44 [1.01 to 27.88] min, P < 0.00001) compared
      to OLR. Less overall morbidity (OR: 0.64 [0.55 to 0.75], p < 0.00001) and shorter
      postoperative hospital stay (WMD: -2.36 [-3.06 to -1.66] d, p < 0.00001) were
      observed for patients undergoing LLR, while there was no statistical difference
      in mortality. LLR appears to be a safe and feasible alternative to OLR in the
      treatment of CCLM in selected patients.

PMID- 28432296
TI  - Aminoglycosides, but not PTC124 (Ataluren), rescue nonsense mutations in the
      leptin receptor and in luciferase reporter genes.
AB  - In rare cases, monogenetic obesity is caused by nonsense mutations in genes
      regulating energy balance. A key factor herein is the leptin receptor. Here, we
      focus on leptin receptor nonsense variants causing obesity, namely the human
      W31X, murine Y333X and rat Y763X mutations, and explored their susceptibilities
      to aminoglycoside and PTC124 mediated translational read-through in vitro. In a
      luciferase based assay, all mutations - when analysed within the mouse receptor -
      were prone to aminoglycoside mediated nonsense suppression with the highest
      susceptibility for W31X, followed by Y763X and Y333X. For the latter, the
      corresponding rodent models appear valuable for in vivo experiments. When W31X
      was studied in the human receptor, its superior read-through susceptibility -
      initially observed in the mouse receptor - was eliminated, likely due to the
      different nucleotide context surrounding the mutation in the two orthologues. The
      impact of the surrounding context on the read-through opens the possibility to
      discover novel sequence elements influencing nonsense suppression. As an
      alternative to toxic aminoglycosides, PTC124 was indicated as a superior nonsense
      suppressor but inconsistent data concerning its read-through activity are
      reported. PTC124 failed to rescue W31X as well as different nonsense mutated
      luciferase reporters, thus, challenging its ability to induce translational read
      through.

PMID- 28432297
TI  - High probability of comorbidities in bronchial asthma in Germany.
AB  - : Clinical experience has shown that allergic and non-allergic respiratory,
      metabolic, mental, and cardiovascular disorders sometimes coexist with bronchial
      asthma. However, no study has been carried out that calculates the chance of
      manifestation of these disorders with bronchial asthma in Saarland and Rhineland
      Palatinate, Germany. Using ICD10 diagnoses from health care institutions, the
      present study systematically analyzed the co-prevalence and odds ratios of
      comorbidities in the asthma population in Germany. The odds ratios were adjusted
      for age and sex for all comorbidities for patients with asthma vs. without
      asthma. Bronchial asthma was strongly associated with allergic and with a lesser
      extent to non-allergic comorbidities: OR 7.02 (95%CI:6.83-7.22) for allergic
      rhinitis; OR 4.98 (95%CI:4.67-5.32) allergic conjunctivitis; OR 2.41 (95%CI:2.33
      2.52) atopic dermatitis; OR 2.47 (95%CI:2.16-2.82) food allergy, and OR 1.69
      (95%CI:1.61-1.78) drug allergy. Interestingly, increased ORs were found for
      respiratory diseases: 2.06 (95%CI:1.64-2.58) vocal dysfunction; 1.83 (95%CI:1.74
      1.92) pneumonia; 1.78 (95%CI:1.73-1.84) sinusitis; 1.71 (95%CI:1.65-1.78)
      rhinopharyngitis; 2.55 (95%CI:2.03-3.19) obstructive sleep apnea; 1.42
      (95%CI:1.25-1.61) pulmonary embolism, and 3.75 (95%CI:1.64-8.53) bronchopulmonary
      aspergillosis. Asthmatics also suffer from psychiatric, metabolic, cardiac or
      other comorbidities. Myocardial infarction (OR 0.86, 95%CI:0.79-0.94) did not
      coexist with asthma. Based on the calculated chances of manifestation for these
      comorbidities, especially allergic and respiratory, to a lesser extent also
      metabolic, cardiovascular, and mental disorders should be taken into
      consideration in the diagnostic and treatment strategy of bronchial asthma.
      BRONCHIAL ASTHMA: PREVALENCE OF CO-EXISTING DISEASES IN GERMANY: Patients in
      Germany with bronchial asthma are highly likely to suffer from co-existing
      diseases and their treatments should reflect this. Quoc Thai Dinh at Saarland
      University Hospital in Homburg, Germany, and co-workers conducted a large-scale
      study of patients presenting with bronchial asthma in the Saarland region between
      2009 and 2012. Patients with asthma made up 5.4% of the region's total
      population, with a higher prevalence occurring in females. They found that
      bronchial asthma was strongly associated with allergic comorbidities such as
      rhinitis. Indeed, asthmatic patients had a seven times higher chance to suffer
      from allergic rhinitis than the rest of the population, and were at higher risk
      of respiratory diseases like pneumonia and obstructive sleep apnea syndrome.
      Further associations included cardiovascular, metabolic and mental disorders.
      Dinh's team call for asthma treatments to take such comorbidities into account.

PMID- 28432298
TI  - Endogenous Two-Photon Excited Fluorescence Imaging Characterizes Neuron and
      Astrocyte Metabolic Responses to Manganese Toxicity.
AB  - As neurodegenerative conditions are increasingly linked to mitochondrial
      dysfunction, methods for studying brain cell metabolism at high spatial
      resolution are needed to elucidate neurodegeneration mechanisms. Two-photon
      excited fluorescence (TPEF) imaging is a non-destructive, high-resolution
      technique for studying cell metabolism via endogenous fluorescence of reduced
      nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine
      dinucleotide (FAD). We employed TPEF to study the metabolism of primary rat
      astrocyte and neuronal cultures under normal growth conditions and in response to
      manganese (Mn) treatment. Histograms of pixel-wise optical redox ratio, defined
      as FAD/(FAD + NAD(P)H), revealed three distinct redox distributions and
      significant differences in their relative weights between astrocytes and neurons.
      When treated with Mn, both cell types exhibited redox ratio shifts consistent
      with increased oxidative stress. However, the manner in which the redox
      distributions was affected was distinct for the two cell types. Furthermore,
      NAD(P)H fluorescence lifetime imaging revealed an increase in bound NAD(P)H
      fraction upon Mn treatment for neurons, consistent with enhanced apoptosis.
      Astrocytes showed a decrease in bound fraction, possibly due to a shift towards
      glycolytic metabolism in response to impaired respiration. These results exhibit
      TPEF's utility for characterizing detailed metabolic changes of different brain
      cell types in response to neurotoxins.

PMID- 28432300
TI  - Entropic uncertainty relations for Markovian and non-Markovian processes under a
      structured bosonic reservoir.
AB  - The uncertainty relation is a fundamental limit in quantum mechanics and is of
      great importance to quantum information processing as it relates to quantum
      precision measurement. Due to interactions with the surrounding environment, a
      quantum system will unavoidably suffer from decoherence. Here, we investigate the
      dynamic behaviors of the entropic uncertainty relation of an atom-cavity
      interacting system under a bosonic reservoir during the crossover between
      Markovian and non-Markovian regimes. Specifically, we explore the dynamic
      behavior of the entropic uncertainty relation for a pair of incompatible
      observables under the reservoir-induced atomic decay effect both with and without
      quantum memory. We find that the uncertainty dramatically depends on both the
      atom-cavity and the cavity-reservoir interactions, as well as the correlation
      time, tau, of the structured reservoir. Furthermore, we verify that the
      uncertainty is anti-correlated with the purity of the state of the observed qubit
      system. We also propose a remarkably simple and efficient way to reduce the
      uncertainty by utilizing quantum weak measurement reversal. Therefore our work
      offers a new insight into the uncertainty dynamics for multi-component
      measurements within an open system, and is thus important for quantum precision
      measurements.

PMID- 28432299
TI  - Tangluoning, a traditional Chinese medicine, attenuates in vivo and in vitro
      diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway.
AB  - Prolonged hyperglycemia-induced oxidative stress and endoplasmic reticulum stress
      have been demonstrated to play a key role in progression of diabetic peripheral
      neuropathy (DPN). PERK/ Nrf2 pathway plays a predominant role in oxidative and
      endoplasmic reticulum (ER) stress which is associated with cell survival. This
      study examined the modulation of the PERK/Nrf2 pathway and apoptosis by a
      traditional Chinese medicine Tangluoning (TLN) in streptozotocin-induced DPN rat
      models and the effects of serum TLN on the PERK/Nrf2 pathway, apoptosis,
      intracellular reactive oxygen species and mitochondrial membrane potential in
      Schwann cells cultured in 150 mM glucose. It is found that TLN attenuated
      oxidative and ER stress and apoptosis through the PERK/Nrf2 pathway by
      upregulating p-PERK, Nrf2/ARE pathways and downregulating the CHOP-related
      apoptosis pathways in the experimental DPN models both in vivo and in vitro.

PMID- 28432301
TI  - AMPK signaling in the nucleus accumbens core mediates cue-induced reinstatement
      of cocaine seeking.
AB  - Relapse to drug seeking can be caused by exposure to drug-associated cues,
      provoking drug craving even after prolonged abstinence. Recent studies
      demonstrated that AMP-activated protein kinase (AMPK) regulates neuronal
      morphology and membrane excitability in neurons. Here, we investigated the role
      of AMPK activity in the nucleus accumbens (NAc) in relapse to cocaine seeking. We
      found that exposure to drug-related cues reinstated cocaine-seeking behavior and
      increased AMPK and p70s6k phosphorylation in the NAc core but not shell.
      Augmenting AMPK activity by intra-NAc core infusions of the AMPK activator 5
      amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) or adenovirus
      expressing constitutively active subunits of AMPK decreased cue-induced
      reinstatement of cocaine seeking and inhibited the mammalian target of rapamycin
      complex 1 (mTORC1) and extracellular signal-regulated kinase 1/2 (ERK1/2)
      pathways. In contrast, inhibition of AMPK activity by intra-NAc core infusions of
      the AMPK inhibitor compound C or adenovirus expressing dominant-negative subunits
      of AMPK increased cue-induced reinstatement of cocaine seeking and enhanced
      mTORC1 and ERK1/2 activity. The regulation of AMPK activity in the NAc shell had
      no effect on cue-induced cocaine seeking. Altogether, these results indicate that
      AMPK activity in the NAc core is critical for the cue-induced reinstatement of
      cocaine seeking, which may be mediated by mTORC1 and ERK1/2 signaling.

PMID- 28432304
TI  - Decreasing temperature enhances the formation of sixfold hydrogen bonded rings in
      water-rich water-methanol mixtures.
AB  - The evolution of the structure of liquid water-methanol mixtures as a function of
      temperature has been studied by molecular dynamics simulations, with a focus on
      hydrogen bonding. The combination of the OPLS-AA (all atom) potential model of
      methanol and the widely used SPC/E water model has provided excellent agreement
      with measured X-ray diffraction data over the temperature range between 298 and
      213 K, for mixtures with methanol molar fractions of 0.2, 0.3 and 0.4. Hydrogen
      bonds (HB-s) have been identified via a combined geometric/energetic, as well as
      via a purely geometric definition. The number of recognizable hydrogen bonded
      ring structures in some cases doubles while lowering the temperature from 298 to
      213 K; the number of sixfold rings increases most significantly. An evolution
      towards the structure of hexagonal ice, that contains only sixfold hydrogen
      bonded rings, has thus been detected on cooling water-methanol mixtures.

PMID- 28432302
TI  - A bacterial ABC transporter enables import of mammalian host glycosaminoglycans.
AB  - Glycosaminoglycans (GAGs), such as hyaluronan, chondroitin sulfate, and heparin,
      constitute mammalian extracellular matrices. The uronate and amino sugar residues
      in hyaluronan and chondroitin sulfate are linked by 1,3-glycoside bond, while
      heparin contains 1,4-glycoside bond. Some bacteria target GAGs as means of
      establishing colonization and/or infection, and bacterial degradation mechanisms
      of GAGs have been well characterized. However, little is known about the
      bacterial import of GAGs. Here, we show a GAG import system, comprised of a
      solute-binding protein (Smon0123)-dependent ATP-binding cassette (ABC)
      transporter, in the pathogenic Streptobacillus moniliformis. A genetic cluster
      responsible for depolymerization, degradation, and metabolism of GAGs as well as
      the ABC transporter system was found in the S. moniliformis genome. This
      bacterium degraded hyaluronan and chondroitin sulfate with an expression of the
      genetic cluster, while heparin repressed the bacterial growth. The purified
      recombinant Smon0123 exhibited an affinity with disaccharides generated from
      hyaluronan and chondroitin sulfate. X-ray crystallography indicated binding mode
      of Smon0123 to GAG disaccharides. The purified recombinant ABC transporter as a
      tetramer (Smon0121-Smon0122/Smon0120-Smon0120) reconstructed in liposomes
      enhanced its ATPase activity in the presence of Smon0123 and GAG disaccharides.
      This is the first report that has molecularly depicted a bacterial import system
      of both sulfated and non-sulfated GAGs.

PMID- 28432303
TI  - Closed-loop deep brain stimulation by pulsatile delayed feedback with increased
      gap between pulse phases.
AB  - Computationally it was shown that desynchronizing delayed feedback stimulation
      methods are effective closed-loop techniques for the control of synchronization
      in ensembles of interacting oscillators. We here computationally design
      stimulation signals for electrical stimulation of neuronal tissue that preserve
      the desynchronizing delayed feedback characteristics and comply with mandatory
      charge deposit-related safety requirements. For this, the amplitude of the high
      frequency (HF) train of biphasic charge-balanced pulses used by the standard HF
      deep brain stimulation (DBS) is modulated by the smooth feedback signals. In this
      way we combine the desynchronizing delayed feedback approach with the HF DBS
      technique. We show that such a pulsatile delayed feedback stimulation can
      effectively and robustly desynchronize a network of model neurons comprising
      subthalamic nucleus and globus pallidus external and suggest this approach for
      desynchronizing closed-loop DBS. Intriguingly, an interphase gap introduced
      between the recharging phases of the charge-balanced biphasic pulses can
      significantly improve the stimulation-induced desynchronization and reduce the
      amount of the administered stimulation. In view of the recent experimental and
      clinical studies indicating a superiority of the closed-loop DBS to open-loop HF
      DBS, our results may contribute to a further development of effective stimulation
      methods for the treatment of neurological disorders characterized by abnormal
      neuronal synchronization.

PMID- 28432305
TI  - Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed
      by Quantitative Phosphoproteomics.
AB  - GLP-1 synergizes with glucose in regulating pancreatic beta-cell function,
      including facilitating beta-cell survival and insulin secretion. Though it has
      been widely accepted that phosphorylation is extremely important in regulating
      beta-cell functions, our knowledge to the global mechanism is still limited. Here
      we performed a quantitative phosphoproteomics study to systematically present the
      synergistic regulation of INS-1E cell phosphoproteome mediated by glucose and GLP
      1. We generated the largest pancreatic beta-cell phosphoproteome by identifying
      25,327 accurately localized phosphorylation sites on 5,389 proteins. Our results
      discovered several novel kinases regulated by glucose, GLP-1 or their synergism,
      and some of these kinases might act as downstream molecules of GLP-1 mediated PKA
      signaling cascade. A few phosphosites were regulated by both GLP-1 and glucose
      alone, and these target proteins were highly related to their biological function
      on pancreatic beta-cells. Finally, we found glucose and GLP-1 executed their
      synergistic effect at multiple levels, especially at pathway level. Both GLP-1
      and glucose participated in regulating every single step of the secretion
      pathway, and systematically synergized their effects in inducing insulin
      secretion.

PMID- 28432306
TI  - Simple Rectangular Gratings as a Near-Field "Anti-Reflection" Pattern for GaSb
      TPV Cells.
AB  - We show theoretically that 2D rectangular gratings on the surface of GaSb can
      serve as an "anti-reflection" pattern for nano-gap thermophotovoltaic (TPV)
      devices, which significantly enhances near-field radiative flux from the emitter
      to a GaSb cell, thus improving output power and conversion efficiency. The system
      in this study is a 200-nm gap TPV power generation system with a planar infrared
      plasmonic emitter and GaSb cell. Rigorous coupled-wave analysis is used to
      calculate the spectral near-field radiative flux involving periodic structures.
      The simulation shows that when coupled with a near-infrared plasmonic bulk
      emitter, adding gratings on the GaSb cell surface results in strong spectral
      enhancement above the cell's bandgap and suppression for low-energy photon
      transmission, an effect that cannot be fully predicted by the effective medium
      theory. The resultant peak spectral heat flux is 2.8 times as high as the case
      without surface structures and the radiative transfer efficiency increased to
      24.8% from the original 14.5% with the emitter temperature at 1800 K. The
      influence of the grating's geometry parameters on the enhancement and peak
      frequency is further discussed with rigorous calculation of the spatial
      distribution of thermal radiative transfer that provided insight into the
      physical mechanism.

PMID- 28432307
TI  - Arsenic metabolism in high altitude modern stromatolites revealed by metagenomic
      analysis.
AB  - Modern stromatolites thrive only in selected locations in the world. Socompa
      Lake, located in the Andean plateau at 3570 masl, is one of the numerous extreme
      Andean microbial ecosystems described over recent years. Extreme environmental
      conditions include hypersalinity, high UV incidence, and high arsenic content,
      among others. After Socompa's stromatolite microbial communities were analysed by
      metagenomic DNA sequencing, taxonomic classification showed dominance of
      Proteobacteria, Bacteroidetes and Firmicutes, and a remarkably high number of
      unclassified sequences. A functional analysis indicated that carbon fixation
      might occur not only by the Calvin-Benson cycle, but also through alternative
      pathways such as the reverse TCA cycle, and the reductive acetyl-CoA pathway.
      Deltaproteobacteria were involved both in sulfate reduction and nitrogen
      fixation. Significant differences were found when comparing the Socompa
      stromatolite metagenome to the Shark Bay (Australia) smooth mat metagenome:
      namely, those involving stress related processes, particularly, arsenic
      resistance. An in-depth analysis revealed a surprisingly diverse metabolism
      comprising all known types of As resistance and energy generating pathways. While
      the ars operon was the main mechanism, an important abundance of arsM genes was
      observed in selected phyla. The data resulting from this work will prove a
      cornerstone for further studies on this rare microbial community.

PMID- 28432309
TI  - Fano resonance with high local field enhancement under azimuthally polarized
      excitation.
AB  - Being an enabling technology for applications such as ultrasensitive biosensing
      and surface enhanced spectroscopy, enormous research interests have been focused
      on further boosting the local field enhancement at Fano resonance. Here, we
      demonstrate a plasmonic Fano resonance resulting from the interference between a
      narrow magnetic dipole mode and a broad electric dipole mode in a split-ring
      resonator (SRR) coupled to a nanoarc structure. Strikingly, when subjected to an
      azimuthally polarized beam (APB) excitation, the intensity enhancement becomes
      more than 60 times larger than that for a linearly polarized beam (LPB). We
      attribute this intensity enhancement to the improved conversion efficiency
      between the excitation and magnetic dipole mode along with improved near-field
      coupling. The APB excited Fano structure is further used as a nanoruler and beam
      misalignment sensor, due to the high sensitivity of intensity enhancement and
      scattering spectra to structure irregularities and excitation beam misalignment.
      Interestingly, we find that, regardless of the presence of structural
      translations, the proposed structure still maintains over 60 times better
      intensity enhancement under APB excitation compared to LPB excitation. Moreover,
      even if the APB excitation is somewhat misaligned, our Fano structure still
      manages to give a larger intensity enhancement than its counterpart excited by
      LPB.

PMID- 28432308
TI  - Network-aided Bi-Clustering for discovering cancer subtypes.
AB  - Bi-clustering is a widely used data mining technique for analyzing gene
      expression data. It simultaneously groups genes and samples of an input gene
      expression data matrix to discover bi-clusters that relevant samples exhibit
      similar gene expression profiles over a subset of genes. The discovered bi
      clusters bring insights for categorization of cancer subtypes, gene treatments
      and others. Most existing bi-clustering approaches can only enumerate bi-clusters
      with constant values. Gene interaction networks can help to understand the
      pattern of cancer subtypes, but they are rarely integrated with gene expression
      data for exploring cancer subtypes. In this paper, we propose a novel method
      called Network-aided Bi-Clustering (NetBC). NetBC assigns weights to genes based
      on the structure of gene interaction network, and it iteratively optimizes sum
      squared residue to obtain the row and column indicative matrices of bi-clusters
      by matrix factorization. NetBC can not only efficiently discover bi-clusters with
      constant values, but also bi-clusters with coherent trends. Empirical study on
      large-scale cancer gene expression datasets demonstrates that NetBC can more
      accurately discover cancer subtypes than other related algorithms.

PMID- 28432310
TI  - Efficacy of alprostadil for preventing of contrast-induced nephropathy: A meta
      analysis.
AB  - Contrast-induced nephropathy (CIN) has become the third-leading cause of hospital
      acquired acute renal injury. Although alprostadil has been proposed as an
      effective preventative measure, this conclusion remains inconsistent. Thus, we
      performed a meta-analysis of the published studies on this topic to evaluate the
      preventative effect of alprostadil on CIN. Databases, including PubMed, the Web
      of Science, Cochrane Library, Wanfang, the China Biological Medicine Database
      (SinoMed) and the China National Knowledge Infrastructure (CNKI) were
      systematically searched. Nineteen clinical trials involving 2267 individuals were
      identified. We utilized a random or a fixed effect model to calculate the pooled
      odd ratios (ORs) and the standardized mean differences (SMD), respectively.
      Compared to the control group, the CIN risk decreased significantly in the
      alprostadil group (P < 0.00001, OR = 0.29, 95% CI = 0.21-0.39). In the subgroup
      of coronary angiography patients, the use of alprostadil also decreased the risk
      of CIN (P < 0.00001, OR = 0.27, 95% CI: 0.19-0.39). In conclusion, Alprostadil
      might be associated with a significant reduction in postcontrast Scr, BUN and
      CysC level and decrease the incidence of CIN.

PMID- 28432311
TI  - Enteric innervation combined with proteomics for the evaluation of the effects of
      chronic fluoride exposure on the duodenum of rats.
AB  - Ingested fluoride (F) is absorbed mainly in the small intestine, which is
      controlled by the Enteric Nervous System (ENS). Although important intestinal
      symptomatology has been described after excessive F exposure, there have been no
      studies reporting the effects of F on the ENS. In this study, the effects of
      chronic F exposure were evaluated on the duodenums of rats through proteomic and
      morphological analyses. Concentrations of 0, 10, or 50 ppm of F were applied to
      the drinking water for 30 days. Immunofluorescence techniques were performed in
      the myenteric plexus of the duodenum to detect HuC/D, neuronal nitric oxide
      (nNOS), vasoactive intestinal peptide (VIP), calcitonin gene related peptide
      (CGRP), and substance P (SP). The 50 ppm F group presented a significant decrease
      in the density of nNOS-IR neurons. Significant morphological alterations were
      also observed in HUC/D-IR and nNOS-IR neurons; VIP-IR, CGRP-IR, and SP-IR
      varicosities for both groups (10 and 50 ppm F). Proteomic analysis of the
      duodenum demonstrated alterations in the expression of several proteins,
      especially those related to important biological processes, such as protein
      polymerization, which helps to explain the downregulation of many proteins upon
      exposure to 50 ppm of F.

PMID- 28432312
TI  - Growth Differentiation Factor-15 Deficiency Augments Inflammatory Response and
      Exacerbates Septic Heart and Renal Injury Induced by Lipopolysaccharide.
AB  - Septic acute kidney injury (AKI) and myocardial dysfunction are leading causes of
      mortality with no accepted method of therapy. In this study we demonstrate the
      role of growth differentiating factor 15 (GDF15) in septic AKI and myocardial
      dysfunction using a murine lipopolysaccharide (LPS)-induced sepsis model and an
      in vitro cell culture system. Data show that GDF15 deficiency augments
      inflammatory response and exacerbates renal and cardiac injury induced by LPS,
      while over-expression of GDF15 protects the kidney and heart from LPS-induced
      organ dysfunction. Therefore, this study highlights the therapeutic potential of
      GDF15 in the treatment of endotoxin-induced sepsis.

PMID- 28432313
TI  - Multiple clinical characteristics separate MED12-mutation-positive and -negative
      uterine leiomyomas.
AB  - Up to 86% of uterine leiomyomas harbour somatic mutations in mediator complex
      subunit 12 (MED12). These mutations have been associated with conventional
      histology, smaller tumour size, and larger number of tumours within the uterus.
      Prior studies, with limited sample sizes, have failed to detect associations
      between other clinical features and MED12 mutations. Here, we prospectively
      collected 763 uterine leiomyomas and the corresponding normal myometrial tissue
      from 244 hysterectomy patients, recorded tumour characteristics, collected
      clinical data from medical records, and screened the tissue samples for MED12
      mutations to assess potential associations between clinical variables and
      mutation status. Out of 763 leiomyomas, 599 (79%) harboured a MED12 mutation. In
      the analysis of tumour characteristics, positive MED12-mutation status was
      significantly associated with smaller tumour size, conventional histology, and
      subserous location, relative to intramural. In the analysis of clinical
      variables, the number of MED12-mutation-positive tumours showed an inverse
      association with parity, and the number of mutation-negative tumours showed a
      positive association with a history of pelvic inflammatory disease. This study
      confirmed the previously reported differences and discovered novel
      differentiating features for MED12-mutation-positive and -negative leiomyomas.
      These findings emphasise the relevance of specific driver mutations in genesis
      and presentation of uterine leiomyomas.

PMID- 28432314
TI  - The effect of acute social stress on the recognition of facial expression of
      emotions.
AB  - This study investigates the effect of acute social stress on the recognition of
      facial expression of emotions in healthy young men. Participants underwent both a
      standardized psychosocial laboratory stressor (TSST-G) and a control condition.
      Then, they performed a homemade version of the facial expressions megamix. All
      six basic emotions were included in the task. First, our results show a
      systematic increase in the intensity threshold for disgust following stress,
      meaning that the participants' performance with this emotion was impaired. We
      suggest that this may reflect an adaptive coping mechanism where participants
      attempt to decrease their anxiety and protect themselves from a socio-evaluative
      threat. Second, our results show a systematic decrease in the intensity threshold
      for surprise, therefore positively affecting the participants' performance with
      that emotion. We suggest that the enhanced perception of surprise following the
      induction of social stress may be interpreted as an evolutionary adaptation,
      wherein being in a stressful environment increases the benefits of monitoring
      signals indicating the presence of a novel or threatening event. An alternative
      explanation may derive from the opposite nature of the facial expressions of
      disgust and surprise; the decreased recognition of disgust could therefore have
      fostered the propensity to perceive surprise.

PMID- 28432315
TI  - Experimental evidence of Fano resonances in nanomechanical resonators.
AB  - Fano resonance refers to an interference between localized and continuum states
      that was firstly reported for atomic physics and solid-state quantum devices. In
      recent years, Fano interference gained more and more attention for its importance
      in metamaterials, nanoscale photonic devices, plasmonic nanoclusters and surface
      enhanced Raman scattering (SERS). Despite such interest in nano-optics, no
      experimental evidence of Fano interference was reported up to now for purely
      nanomechanical resonators, even if classical mechanical analogies were referred
      from a theoretical point of view. Here we demonstrate for the first time that
      harmonic nanomechanical resonators with relatively high quality factors, such as
      cantilevers vibrating in vacuum, can show characteristic Fano asymmetric curves
      when coupled in arrays. The reported findings open new perspectives in
      fundamental aspects of classical nanomechanical resonators and pave the way to a
      new generation of chemical and biological nanoresonator sensors with higher
      parallelization capability.

PMID- 28432316
TI  - How visual experience impacts the internal and external spatial mapping of
      sensorimotor functions.
AB  - Tactile perception and motor production share the use of internally- and
      externally-defined coordinates. In order to examine how visual experience affects
      the internal/external coding of space for touch and movement, early blind (EB)
      and sighted controls (SC) took part in two experiments. In experiment 1,
      participants were required to perform a Temporal Order Judgment task (TOJ),
      either with their hands in parallel or crossed over the body midline. Confirming
      previous demonstration, crossing the hands led to a significant decrement in
      performance in SC but did not affect EB. In experiment 2, participants were
      trained to perform a sequence of five-finger movements. They were tested on their
      ability to produce, with the same hand but with the keypad turned upside down,
      the learned (internal) or the mirror (external) sequence. We observed significant
      transfer of motor sequence knowledge in both EB and SC irrespective of whether
      the representation of the sequence was internal or external. Together, these
      results demonstrate that visual experience differentially impacts the automatic
      weight attributed to internal versus external coordinates depending on task
      specific spatial requirements.

PMID- 28432317
TI  - Psiguajadials A-K: Unusual Psidium Meroterpenoids as Phosphodiesterase-4
      Inhibitors from the Leaves of Psidium guajava.
AB  - Bioassay-guided fractionation of the ethanolic extract of the leaves of Psidium
      guajava led to the isolation of 11 new Psidium meroterpenoids, psiguajadials A-K
      (1-11), along with 17 known ones (12-28). Their structures and absolute
      configurations were elucidated by spectroscopic methods and comparison of
      experimental and calculated ECD. Compounds 1 and 2 represent two unprecedented
      skeletons of 3,5-diformyl-benzyl phloroglucinol-coupled sesquiterpenoid, while 3
      is the first example of Psidium meroterpenoids coupling via an oxepane ring.
      Putative biosynthetic pathways towards 1 and 2 are proposed. Compounds 1-13 and
      16-26 exhibited moderate inhibitory activities against phosphodiesterase-4
      (PDE4), a drug target for asthma and chronic obstructive pulmonary disease, with
      IC50 values in the range of 1.34-7.26 MUM.

PMID- 28432318
TI  - Orbital angular momentum (OAM) conversion and multicasting using N-core supermode
      fiber.
AB  - We propose and numerically demonstrate a conversion and multicasting scheme of
      orbital angular momentum (OAM) states by using N-core supermode fiber (NCSF),
      where the topological charges of converted OAM states mainly depend on the
      injected OAM state and the number of fiber cores. The conversion efficiency (CE)
      of the converted OAM states could be optimized by properly designing the fiber
      structure. Take N = 6 as an example, ~37% CE could be achieved at telecom bands.
      Moreover, even for a fabricated NCSF, the CE could be dynamically changed by
      stretching the fiber or by adjusting the refractive index of the fiber cores
      through external control of the environmental conditions. Meanwhile, OAM
      multicasting could also be realized in the designed NCSF. The crosstalk between
      the multicasted OAM channels and their neighboring ones are assessed to be less
      than -30 dB. The proposed fiber-based OAM conversion and multicasting system is
      compatible with the existing optical fiber communication systems, showing
      potential applications in the future.

PMID- 28432319
TI  - Diabetic Retinopathy and Clinical Parameters Favoring the Presence of Diabetic
      Nephropathy could Predict Renal Outcome in Patients with Diabetic Kidney Disease.
AB  - Diabetes duration, diabetic retinopathy (DR), and a diagnostic model have been
      proposed as clinical parameters favoring the presence of diabetic nephropathy
      (DN) in biopsied patients with diabetic kidney disease. DN, compared with non
      diabetic renal disease, had poorer renal outcomes. We tested whether these
      clinical parameters favoring DN are associated with poorer renal outcomes in non
      biopsied patients. In this study, 1330 patients with type 2 diabetes and chronic
      kidney disease stages 1-4 were included and divided according to diabetes
      mellitus (DM) duration >8 years, DR, or a diagnostic model for DN. These clinical
      parameters favoring DN were found in 62-77% of patients and associated with
      higher levels of proteinuria. In a Cox survival analysis, DR and the diagnostic
      model favoring DN were associated with an increased risk for end-stage renal
      disease with adjusted hazard ratios of 1.69 (95% CI: 1.16-2.45, P = 0.006) and
      1.66 (95% CI: 1.05-2.61, P = 0.029), respectively. DR was associated with an
      increased risk for rapid renal disease progression. DM >8 years was not
      associated with renal outcome. Propensity score-matched analyses also showed
      similar results. In conclusion, DR and the diagnostic model favoring DN were
      associated with poorer renal outcomes.

PMID- 28432320
TI  - Formation of CuO nano-flowered surfaces via submerged photo-synthesis of
      crystallites and their antimicrobial activity.
AB  - We report the fabrication of flower-like CuO nanostructured surfaces via
      submerged photo-synthesis of crystallites (SPSC), which requires only UV
      illumination in neutral water. In this paper, we discuss the reaction mechanism
      of the photochemical formation of the SPSC-fabricated CuO nanostructures in
      detail based on surface microstructural analyses and a radiation-chemical
      consideration with additional gamma-ray irradiation. Since the SPSC method for
      surface nanostructural fabrication can work at low temperatures at atmospheric
      pressure without using harmful substances, it is a potential fabrication method
      for green nanotechnology applications. In this vein, the antibacterial activity
      of the nano-flowered CuO surfaces was tested against Gram-positive
      (Staphylococcus aureus) bacteria and Gram-negative (Escherichia coli K12)
      bacteria, and the results demonstrate that the nano-flowered CuO nanostructures
      act as an effective antimicrobial agent.

PMID- 28432321
TI  - Mycobacterium tuberculosis Lineage Distribution in Xinjiang and Gansu Provinces,
      China.
AB  - Mycobacterium tuberculosis (M. tuberculosis) genotyping has dramatically improved
      the understanding of the epidemiology of tuberculosis (TB). In this study, 187 M.
      tuberculosis isolates from Xinjiang Uygur Autonomous Region (Xinjiang) and Gansu
      province in China were genotyped using large sequence polymorphisms (LSPs) and
      variable number tandem repeats (VNTR). Ten isolates, which represent major nodes
      of VNTR-based minimum spanning tree, were selected and subsequently subjected to
      multi-locus sequence analyses (MLSA) that include 82 genes. Based on a robust
      lineage assignment, we tested the association between lineages and clinical
      characteristics by logistic regression. There are three major lineages of M.
      tuberculosis prevalent in Xinjiang, viz. the East Asian Lineage 2 (42.1%;
      56/133), the Euro-American Lineage 4 (33.1%; 44/133), and the Indian and East
      African Lineage 3 (24.8%; 33/133); two lineages prevalent in Gansu province,
      which are the Lineage 2 (87%; 47/54) and the Lineage 4 (13%; 7/54). The
      topological structures of the MLSA-based phylogeny support the LSP-based
      identification of M. tuberculosis lineages. The statistical results suggest an
      association between the Lineage 2 and the hemoptysis/bloody sputum symptom, fever
      in Uygur patients. The pathogenicity of the Lineage 2 remains to be further
      investigated.

PMID- 28432322
TI  - Histological, chemical and behavioural evidence of pedal communication in brown
      bears.
AB  - Most mammals rely upon scent for intraspecific communication. As most bear
      species have large home ranges and are non-territorial, scent deposit while
      walking could be an effective way to communicate with conspecifics. Here, we
      investigate the existence of pedal glands in brown bears and their role in
      chemical communication from a histological, biochemical and behavioural
      perspective. We found eccrine glands in footpads, and prominent apocrine and
      sebaceous glands in the interdigital, metacarpal and metatarsal skin sections.
      Pedal scent contained 26 compounds including carboxylic acids, important
      constituents of mammalian secretions. Six of these compounds were exclusive for
      males. Finally, we describe a specific marking gait recorded in the field, mostly
      performed by males. Our study supports the existence of chemical communication
      through pedal marking in brown bears and suggests sex-coding potential of pedal
      scent.

PMID- 28432323
TI  - Refractive index tomograms and dynamic membrane fluctuations of red blood cells
      from patients with diabetes mellitus.
AB  - In this paper, we present the optical characterisations of diabetic red blood
      cells (RBCs) in a non-invasive manner employing three-dimensional (3-D)
      quantitative phase imaging. By measuring 3-D refractive index tomograms and 2-D
      time-series phase images, the morphological (volume, surface area and
      sphericity), biochemical (haemoglobin concentration and content) and mechanical
      (membrane fluctuation) parameters were quantitatively retrieved at the individual
      cell level. With simultaneous measurements of individual cell properties,
      systematic correlative analyses on retrieved RBC parameters were also performed.
      Our measurements show there exist no statistically significant alterations in
      morphological and biochemical parameters of diabetic RBCs, compared to those of
      healthy (non-diabetic) RBCs. In contrast, membrane deformability of diabetic RBCs
      is significantly lower than that of healthy, non-diabetic RBCs. Interestingly,
      non-diabetic RBCs exhibit strong correlations between the elevated glycated
      haemoglobin in RBC cytoplasm and decreased cell deformability, whereas diabetic
      RBCs do not show correlations. Our observations strongly support the idea that
      slow and irreversible glycation of haemoglobin and membrane proteins of RBCs by
      hyperglycaemia significantly compromises RBC deformability in diabetic patients.

PMID- 28432325
TI  - Chemical and Electrochemical Synthesis of Platinum Black.
AB  - We present electrochemical and chemical synthesis of platinum black at room
      temperature in aqueous and non-aqueous media. X-ray analysis established the
      purity and crystalline nature. The electron micrographs indicate that the
      nanostructures consist of platinum crystals that interconnect to form porous
      assemblies. Additionally, the electron micrographs of the platinum black thin
      layer, which was electrochemically deposited on different metallic and
      semiconductive substrates (aluminium, platinum, silver, gold, tin-cooper alloy,
      indium-tin-oxide, stainless steel, and copper), indicate that the substrate
      influences its porous features but not its absorbance characteristics. The
      platinum black exhibited a broad absorbance and low reflectance in the
      ultraviolet, visible, and infrared regions. These characteristics make this
      material suitable for use as a high-temperature resistant absorber layer for the
      fabrication of microelectronics.

PMID- 28432324
TI  - Optimization of amino acid replacement costs by mutational pressure in bacterial
      genomes.
AB  - Mutations are considered a spontaneous and random process, which is important
      component of evolution because it generates genetic variation. On the other hand,
      mutations are deleterious leading to non-functional genes and energetically
      costly repairs. Therefore, one can expect that the mutational pressure is
      optimized to simultaneously generate genetic diversity and preserve genetic
      information. To check if empirical mutational pressures are optimized in these
      ways, we compared matrices of nucleotide mutation rates derived from bacterial
      genomes with their best possible alternatives that minimized or maximized costs
      of amino acid replacements associated with differences in their physicochemical
      properties (e.g. hydropathy and polarity). It should be noted that the studied
      empirical nucleotide substitution matrices and the costs of amino acid
      replacements are independent because these matrices were derived from sites free
      of selection on amino acid properties and the amino acid costs assumed only amino
      acid physicochemical properties without any information about mutation at the
      nucleotide level. Obtained results indicate that the empirical mutational
      matrices show a tendency to minimize costs of amino acid replacements. It implies
      that bacterial mutational pressures can evolve to decrease consequences of amino
      acid substitutions. However, the optimization is not full, which enables
      generation of some genetic variability.

PMID- 28432326
TI  - A novel mechanism linking memory stem cells with innate immunity in protection
      against HIV-1 infection.
AB  - HIV infection affects 37 million people and about 1.7 million are infected
      annually. Among the phase III clinical trials only the RV144 vaccine trial
      elicited significant protection against HIV-1 acquisition, but the efficacy and
      immune memory were inadequate. To boost these vaccine functions we studied T stem
      cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic
      markers of CD4+ T cells and they were further characterised into 4 subsets. These
      expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti
      viral restriction factors, both of which were upregulated. In contrast, CD4+ TSCM
      cells expressing CCR5 co-receptors and alpha4beta7 mucosal homing integrins were
      decreased. A parallel increase in CD4+ T cells was recorded with IL-15 receptors,
      APOBEC3G and CC chemokines, the latter downmodulating CCR5 molecules. We suggest
      a novel mechanism of dual memory stem cells; the established sequential memory
      pathway, TSCM ->Central ->Effector memory CD4+ T cells and the innate pathway
      consisting of the 4 subsets of TSCM. Both pathways are likely to be activated by
      endogenous HSP70. The TSCM memory stem cell and innate immunity pathways have to
      be optimised to boost the efficacy and immune memory of protection against HIV-1
      in the clinical trial.

PMID- 28432327
TI  - Genotyping Brucella canis isolates using a highly discriminatory multilocus
      variable-number tandem-repeat analysis (MLVA) assay.
AB  - Differentiation of Brucella canis from other Brucella species are mainly
      performed through PCR-based methods and multilocus variable-number tandem-repeat
      (VNTR) analysis (MLVA) procedures. Both PCR-based and MLVA methods are limited in
      discriminating B. canis strains. A new MLVA-13Bc method for B. canis genotyping
      was established by combining eight newly-developed VNTRs with five published
      ones. During 2010 and 2016, 377 B. canis PCR-positives were identified from 6,844
      canine blood samples from 22 U.S. states, resulting in 229 B. canis isolates. The
      MLVA-13Bc method was able to differentiate each of these 229 isolates. The Hunter
      Gaston Discriminatory Index of the individual VNTR loci ranged from 0.516 to
      0.934 and the combined discriminatory index reached 1.000. Three major clusters
      (A, B and C) and 10 genotype groups were identified from the 229 B. canis
      isolates. Cluster A mainly contains genotype groups 1 and 2, and a few group 3
      isolates; nearly all Cluster B isolates were from group 6; other genotype groups
      were classified into Cluster C. Our newly developed MLVA-13Bc assay is a highly
      discriminatory assay for B. canis genotyping, and can serve as a useful molecular
      epidemiological tool, especially for tracing the source of contamination in an
      event of a B. canis outbreak.

PMID- 28432328
TI  - Tactile Flow Overides Other Cues To Self Motion.
AB  - Vestibular-somatosensory interactions are pervasive in the brain but it remains
      unclear why. Here we explore the contribution of tactile flow to processing self
      motion. We assessed two aspects of self-motion: timing and speed. Participants
      sat on an oscillating swing and either kept their hands on their laps or rested
      them lightly on an earth-stationary surface. They viewed a grating oscillating at
      the same frequency as their motion and judged its phase or, in a separate
      experiment, its speed relative to their perceived motion. Participants required
      the phase to precede body movement (with or without tactile flow) or tactile flow
      by ~5 degrees  (44 ms) to appear earth-stationary. Speed judgments were 4-10%
      faster when motion was from tactile flow, either alone or with body motion,
      compared to body motion alone (where speed judgments were accurate). By comparing
      response variances we conclude that phase and speed judgments do not reflect
      optimal integration of tactile flow with other cues to body motion: instead
      tactile flow dominates perceived self-motion - acting as an emergency override.
      This may explain why even minimal tactile cues are so helpful in promoting
      stability and suggests that providing artificial tactile cues might be a powerful
      aid to perceiving self-motion.

PMID- 28432329
TI  - Affinity biosensors using recombinant native membrane proteins displayed on
      exosomes: application to botulinum neurotoxin B receptor.
AB  - The development of simple molecular assays with membrane protein receptors in a
      native conformation still represents a challenging task. Exosomes are
      extracellular vesicles which, due to their stability and small size, are suited
      for analysis in various assay formats. Here, we describe a novel approach to sort
      recombinant fully native and functional membrane proteins to exosomes using a
      targeting peptide. Specific binding of high affinity ligands to the potassium
      channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin
      type B (BoNT/B) receptor, indicated their correct assembly and outside out
      orientation in exosomes. We then developed, using a label-free optical biosensor,
      a new method to determine the kinetic constants of BoNT/B holotoxin binding to
      its receptor synaptotagmin2/GT1b ganglioside (kon = 2.3 *105 M-1.s-1, koff = 1.3
      10-4 s-1), yielding an affinity constant (KD = 0.6 nM) similar to values
      determined from native tissue. In addition, the recombinant binding domain of
      BoNT/B, a potential vector for neuronal delivery, bound quasi-irreversibly to
      synaptotagmin 2/GT1b exosomes. Engineered exosomes provide thus a novel means to
      study membrane proteins for biotechnology and clinical applications.

PMID- 28432331
TI  - Nontrivial nonradiating all-dielectric anapole.
AB  - Dynamic anapole is a promising element for future nonradiating devices, such as
      cloaked sources and sensors, quantum emitters, and especially the sources for
      observing dynamic Aharonov-Bohm effect. However, the anapole response can be
      damped by the Joule losses. In this paper we theoretically propose and
      experimentally demonstrate a novel type of active all-dielectric source, which is
      in some sense, realizes the elementary anapole of Afanasiev, and study its
      radiative/nonradiative regimes in the microwave range.

PMID- 28432330
TI  - Enhanced Response of Metformin towards the Cancer Cells due to Synergism with
      Multi-walled Carbon Nanotubes in Photothermal Therapy.
AB  - Converging evidence from laboratory models pointed that the widely used
      antidiabetic drug metformin has direct effects on cancer cells. Thus far,
      relatively little attention has been addressed to the drug exposures used
      experimentally relative to those achievable clinically. Here, we demonstrated
      that metformin loaded on carbon nanotubes under near-infrared (NIR) irradiation
      led to the remarkably enhancement in response towards cancer cells. The dose of
      metformin has reduced to only 1/280 of typical doses in monotherapy (35: 10 000
      30 000 uM) where the realization of metformin in conventional antidiabetic doses
      for cancer therapies becomes possible. The heat generated from carbon nanotubes
      upon NIR irradiation has mediated a strong and highly localized hyperthermia-like
      condition that facilitated the enhancement. Our work highlight the promise of
      using highly localized heating from carbon nanotubes to intensify the efficacy of
      metformin for potential cancer therapies.

PMID- 28432332
TI  - Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by
      thyroid status.
AB  - Thyroid disorders cause abnormal puberty, indicating interactions between the
      hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG)
      axes, which are important in pubertal development. The hypothalamic gonadotropin
      inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal
      stage, suggesting the role of GnIH on pubertal onset. Here, we investigated
      whether thyroid dysfunction affects pubertal onset in female mice via GnIH
      regulation. Hypothyroidism showed delayed pubertal onset with increased GnIH
      expression and reduced pituitary-gonadal activity. Remarkably, knockout of GnIH
      prevented the effect of hypothyroidism to delay the pubertal onset, resulting in
      indistinguishable pubertal timing in GnIH-knockout female mice between control
      and hypothyroidism-induced group, indicating that increased GnIH expression
      induced by hypothyroidism may lead to delayed puberty. In contrast,
      hyperthyroidism led to a decrease in GnIH expression, however pubertal onset was
      normal, implying further reduction of the inhibitory GnIH had little effect on
      the phenotypical change. Critically, thyroid hormone suppressed GnIH expression
      in hypothalamic explants and GnIH neurons expressed thyroid hormone receptors to
      convey the thyroid status. Moreover, the thyroid status highly regulated the
      chromatin modifications of GnIH promoter, H3acetylation and H3K9tri-methylation.
      These findings indicate a novel function of GnIH to mediate HPT-HPG interactions
      that contribute to proper pubertal development.

PMID- 28432333
TI  - Metabolomic and Proteomic Analysis of Maize Embryonic Callus induced from
      immature embryo.
AB  - The low ratio of embryonic callus (EC) induction has inhibited the rapid
      development of maize genetic engineering. Still, little is known to explain the
      genotype-dependence of EC induction. Here, we performed a large-scale,
      quantitative analysis of the maize EC metabolome and proteome at three typical
      induction stages in two inbred lines with a range of EC induction capabilities.
      Comparison of the metabolomes and proteomes suggests that the differential
      molecular responses begin at an early stage of development and continue
      throughout the process of EC formation. The two inbred lines show different
      responses under various conditions, such as metal ion binding, cell enlargement,
      stem cell formation, meristematic activity maintenance, somatic embryogenesis,
      cell wall synthesis, and hormone signal transduction. Furthermore, the
      differences in hormone (auxin, cytokinin, gibberellin, salicylic acid, jasmonic
      acid, brassinosteroid and ethylene) synthesis and transduction ability could
      partially explain the higher EC induction ratio in the inbred line 18-599R.
      During EC formation, repression of the "histone deacetylase 2 and ERF
      transcription factors" complex in 18-599R activated the expression of downstream
      genes, which further promoted EC induction. Together, our data provide new
      insights into the molecular regulatory mechanism responsible for efficient EC
      induction in maize.

PMID- 28432334
TI  - Regulation of viral gene expression by duck enteritis virus UL54.
AB  - Duck enteritis virus (DEV) UL54 is a homologue of human herpes simplex virus-1
      (HSV-1) ICP27, which plays essential regulatory roles during infection. Our
      previous studies indicated that DEV UL54 is an immediate-early protein that can
      shuttle between the nucleus and the cytoplasm. In the present study, we found
      that UL54-deleted DEV (DEV-DeltaUL54) exhibits growth kinetics, a plaque size and
      a viral DNA copy number that are significantly different from those of its parent
      wild-type virus (DEV-LoxP) and the revertant (DEV-DeltaUL54 (Revertant)).
      Relative viral mRNA levels, reflecting gene expression, the transcription phase
      and the translation stage, are also significantly different between DEV-DeltaUL54
      infected cells and DEV-LoxP/DEV-DeltaUL54 (Revertant)-infected cells. However,
      the localization pattern of UL30 mRNA is obviously changed in DEV-DeltaUL54
      infected cells. These findings suggest that DEV UL54 is important for virus
      growth and may regulate viral gene expression during transcription, mRNA export
      and translation.

PMID- 28432335
TI  - Policy coherence, integration, and proportionality in tobacco control: Should
      tobacco sales be limited to government outlets?
AB  - Multiple factors, including marijuana decriminalization/legalization, tobacco
      endgame discourse, and alcohol industry pressures, suggest that the retail
      regulatory environment for psychoactive or addictive substances is a dynamic one
      in which new options may be considered. In most countries, the regulation of
      tobacco, marijuana, and alcohol is neither coherent, nor integrated, nor
      proportional to the potential harms caused by these substances. We review the
      possible consequences of restricting tobacco sales to outlets run by government
      operated alcohol retail monopolies, as well as the likely obstacles to such a
      policy. Such a move would allow governments more options for regulating tobacco
      sales, and increase coherence, integration, and proportionality of substance
      regulation. It might also serve as an incremental step toward an endgame goal of
      eliminating sales of commercial combustible tobacco.

PMID- 28432336
TI  - Structure-function analysis of the DNA-binding domain of a transmembrane
      transcriptional activator.
AB  - The transmembrane DNA-binding protein CadC of E. coli, a representative of the
      ToxR-like receptor family, combines input and effector domains for signal sensing
      and transcriptional activation, respectively, in a single protein, thus
      representing one of the simplest signalling systems. At acidic pH in a lysine
      rich environment, CadC activates the transcription of the cadBA operon through
      recruitment of the RNA polymerase (RNAP) to the two cadBA promoter sites, Cad1
      and Cad2, which are directly bound by CadC. However, the molecular details for
      its interaction with DNA have remained elusive. Here, we present the crystal
      structure of the CadC DNA-binding domain (DBD) and show that it adopts a winged
      helix-turn-helix fold. The interaction with the cadBA promoter site Cad1 is
      studied by using nuclear magnetic resonance (NMR) spectroscopy, biophysical
      methods and functional assays and reveals a preference for AT-rich regions. By
      mutational analysis we identify amino acids within the CadC DBD that are crucial
      for DNA-binding and functional activity. Experimentally derived structural models
      of the CadC-DNA complex indicate that the CadC DBD employs mainly non-sequence
      specific over a few specific contacts. Our data provide molecular insights into
      the CadC-DNA interaction and suggest how CadC dimerization may provide high
      affinity binding to the Cad1 promoter.

PMID- 28432337
TI  - Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous
      Chemotactic Responses to Multiple Chemokines.
AB  - We describe a novel protocol to quantitatively and simultaneously compare the
      chemotactic responses of cells towards different chemokines. In this protocol,
      droplets of agarose gel containing different chemokines are applied onto the
      surface of a Petri dish, and then immersed under culture medium in which cells
      are suspended. As chemokine molecules diffuse away from the spot, a transient
      chemoattractant gradient is established across the spots. Cells expressing the
      corresponding cognate chemokine receptors migrate against this gradient by
      crawling under the agarose spots towards their centre. We show that this
      migration is chemokine-specific; meaning that only cells that express the cognate
      chemokine cell surface receptor, migrate under the spot containing its
      corresponding chemokine ligand. Furthermore, we show that migration under the
      agarose spot can be modulated by selective small molecule antagonists present in
      the cell culture medium.

PMID- 28432338
TI  - Crispr/Cas9 Mediated Inactivation of Argonaute 2 Reveals its Differential
      Involvement in Antiviral Responses.
AB  - RNA silencing constitutes an important antiviral mechanism in plants. Small RNA
      guided Argonaute proteins fulfill essential role in this process by acting as
      executors of viral restriction. Plants encode multiple Argonaute proteins of
      which several exhibit antiviral activities. A recent addition to this group is
      AGO2. Its involvement in antiviral responses is established predominantly by
      studies employing mutants of Arabidopsis thaliana. In the virological model
      plant, Nicotiana benthamiana, the contribution of AGO2 to antiviral immunity is
      much less certain due to the lack of appropriate genetic mutants. Previous
      studies employed various RNAi based tools to down-regulate AGO2 expression.
      However, these techniques have several disadvantages, especially in the context
      of antiviral RNA silencing. Here, we have utilized the CRISPR/Cas9 technology to
      inactivate the AGO2 gene of N. benthamiana. The ago2 plants exhibit differential
      sensitivities towards various viruses. AGO2 is a critical component of the
      plants' immune responses against PVX, TuMV and TCV. In contrast, AGO2 deficiency
      does not significantly influence the progression of tombusvirus and CMV
      infections. In summary, our work provides unequivocal proof for the virus
      specific antiviral role of AGO2 in a plant species other than A. thaliana for the
      first time.

PMID- 28432339
TI  - Multifunctional substrate of label-free electrochemical immunosensor for
      ultrasensitive detection of cytokeratins antigen 21-1.
AB  - Poly(thionine)-Au, a novel multifunctional substrate with excellent redox signal,
      enzyme-like activity, and easy antibody immobilisation, was synthesised using
      HAuCl4 as the oxidising agent and thionine as the monomer. The prepared
      poly(thionine)-Au composite exhibited an admirable electrochemical redox signal
      at -0.15 V and excellent H2O2 catalytic ability. In addition, gold nanoparticles
      in this composite were found to directly immobilise antibodies and further
      improve conductivity. In addition, a label-free electrochemical immunosensor was
      developed using poly(thionine)-Au as the sensing substrate for ultrasensitive
      detection of cytokeratin antigen 21-1 (CYFRA 21-1), an immunoassay found in human
      serum. The prepared immunosensor showed a wide liner range from 100 ng mL-1 to 10
      fg mL-1 and an ultralow detection limit of 4.6 fg mL-1 (the ratio of signal to
      noise (S/N) = 3). Additionally, this method was used to analyse human serum
      samples and yielded results consistency with those of ELISA, implying its
      potential application in clinical research. The poly(thionine)-Au composite can
      be easily extended to other polymer-based nanocomposites, which is significant
      for other electrochemical immunoassays.

PMID- 28432340
TI  - Phenome-wide association study for CYP2A6 alleles: rs113288603 is associated with
      hearing loss symptoms in elderly smokers.
AB  - To identify novel phenotypic associations related to Cytochrome P450 Family 2
      Subfamily A Member 6 (CYP2A6), we investigated the human phenome in a total of
      11,271 individuals. Initially, we conducted a phenome-wide association study in
      3,401 nicotine-exposed elderly subjects considering 358 phenotypic traits. We
      identified a significant association between CYP2A6 rs113288603 and hearing loss
      symptoms (p = 5.75 * 10-5). No association was observed in a sample of 3,245
      nicotine-unexposed individuals from the same discovery cohort, consistent with
      the conclusion that the finding is related to CYP2A6 involvement in nicotine
      metabolism. Consistent results were obtained (p < 0.1) in an independent sample
      of 2,077 nicotine-exposed elderly subjects, and similarly, no significance was
      observed in the nicotine-unexposed sample (n = 2,548) of the replication cohort.
      Additional supporting evidence for this association was provided by gene
      expression data: rs113288603 is associated with increased CYP2A6 expression in
      cerebellar hemispheres (p = 7.8 * 10-4). There is a well-known correlation
      between smoking and age-related hearing loss. Cigarette smoking is associated
      with structural changes in the brain and CYP2A6 mediates these changes. In this
      context, the regulatory role of rs113288603 in cerebellum appears to be
      consistent with the known involvement of this brain region in auditory function.

PMID- 28432341
TI  - Detection of red blood cell surface antigens by probe-triggered cell collision
      and flow retardation in an autonomous microfluidic system.
AB  - Microfluidic devices exploit combined physical, chemical and biological phenomena
      that could be unique in the sub-millimeter dimensions. The current goal of
      development of Point-of-Care (POC) medical devices is to extract the biomedical
      information from the blood. We examined the characteristics of blood flow in
      autonomous microfluidic devices with the aim to realize sensitive detection of
      interactions between particulate elements of the blood and the appropriately
      modified surfaces of the system. As a model experiment we demonstrated the fast
      analysis of the AB0 blood group system. We observed that the accumulation of red
      blood cells immobilized on the capillary wall leads to increased lateral movement
      of the flowing cells, resulting in the overall selective deceleration of the red
      blood cell flow column compared to the plasma fraction. We showed that by
      monitoring the flow rate characteristics in capillaries coated with blood type
      reagents it is possible to identify red blood cell types. Analysis of
      hydrodynamic effects governing blood flow by Finite Element Method based
      modelling supported our observations. Our proof-of-concept results point to a
      novel direction in blood analysis in autonomous microfluidic systems and also
      provide the basis for the construction of a simple quantitative device for blood
      group determination.

PMID- 28432342
TI  - Hypermethylation of Interferon Regulatory Factor 8 (IRF8) Confers Risk to Vogt
      Koyanagi-Harada Disease.
AB  - Aberrant methylation change of IRF8 confers risk to various tumors, and abnormal
      expression of IRF8 is involved in many autoimmune diseases, including ocular
      Behcet's disease. However, whether the methylation change of IRF8 is associated
      with Vogt-Koyanagi-Harada (VKH) disease remains unknown. In the present study, we
      found a decreased IRF8 mRNA expression in association with a higher methylation
      level in monocyte-derived dendritic cells (DCs) from active VKH patients compared
      with the normal and inactive subjects. DCs incubated with cyclosporin a (CsA) or
      dexamethasone (DEX) showed a lower methylation and higher mRNA expression of IRF8
      in active VKH patients. A demethylation reagent, 5-Aza-2'-deoxycytidine (DAC)
      showed a notable demethylation effect as evidenced by increasing the mRNA
      expression and reducing the methylation level of IRF8. It also suppressed the Th1
      and Th17 responses through down-regulating the expression of co-stimulatory
      molecules (CD86, CD80, CD40), and reducing the production of pro-inflammatory
      cytokines (IL-6, IL-1beta, IL-23, IL-12) produced by DCs. These findings shows
      that hypermethylation of IRF8 in DCs confers risk to VKH disease. Demethylation
      of IRF8 may offer a novel therapeutic strategy protect against VKH disease.

PMID- 28432343
TI  - COX-1/PGE2/EP4 alleviates mucosal injury by upregulating beta-arr1-mediated Akt
      signaling in colitis.
AB  - COX-1/PGE2 is an important protective mediator in ulcerative colitis (UC). beta
      arrestin1 (beta-arr1), which acts as a scaffold protein, is involved in PGE2
      mediated signaling pathways. However, the interaction between PGE2 and beta-arr1
      in maintaining mucosal barrier integrity remains unexplored. In this study, we
      demonstrated that COX-1 and PGE2 were significantly decreased, and EP4 mRNA was
      downregulated in both UC patients and mice during the injury phase. PGE2
      treatment was found to alleviate mucosal injury and induce EP4 expression during
      dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) mice. Following
      DSS-induced injury, beta-arr1 deficient mice showed increased signs of colitis
      compared to beta-arr1 WT mice, and the expression of PI3K and p-Akt were
      remarkably downregulated in beta-arr1 deficient mice. In parallel, HCT116 cells
      transfected with beta-arr1 siRNA were examined in the presence or absence of PGE2
      in vitro. PGE2 treatment in the beta-arr1 WT/KO DSS model and beta-arr1 siRNA
      transfection of HCT116 cells confirmed that PGE2 upregulated beta-arr1 in vivo
      and in vitro. Collectively, our results indicate that COX-1/PGE2/EP4 upregulates
      the beta-arr1 mediated Akt signaling pathway to provide mucosal protection in
      colitis. Thus, these findings provide support for the future development and
      clinical application of COX-1/PGE2 in UC.

PMID- 28432344
TI  - Aptamer- Based Label-Free Electrochemical Biosensor Array for the Detection of
      Total and Glycated Hemoglobin in Human Whole Blood.
AB  - The increase of the level of glucose in blood leads to an increase in the
      fraction of glycated hemoglobin (HbA1c). Therefore, the percentage of HbA1c in
      the blood can serve as a marker for the average glucose level over the past three
      months and thus, it can be used to diagnose diabetes. Here, we report the
      selection, identification and characterization of specific DNA aptamers against
      HbA1c- and total hemoglobin (tHb) and their integration into an electrochemical
      array sensing platform. High affinity and specificity aptamers were selected in
      vitro showing dissociation constants of 2.8 and 2.7 nM for HbA1c and tHb,
      respectively. Thiol-modified forms of the aptamers were then immobilised on gold
      nanoparticles (AuNPs)-modified array electrodes and used for the label-free
      detection of HbA1c and tHb using square wave voltammetry. The voltammetric
      aptasensors showed high sensitivity with detection limits of 0.2 and 0.34 ng/ml
      for HbA1c and tHb, respectively. This array platform is superior to the currently
      available immunoassays in terms of simplicity, stability, ease of use, reduction
      of sample volume and low cost. Moreover, this method enabled the detection of
      HbA1c % in human whole blood without any pre-treatment, suggesting great promise
      of this platform for the diagnosis of diabetes.

PMID- 28432345
TI  - Distant Phe345 mutation compromises the stability and activity of Mycobacterium
      tuberculosis isocitrate lyase by modulating its structural flexibility.
AB  - Isocitrate lyase (ICL), a potential anti-tubercular drug target, catalyzes the
      first step of the glyoxylate shunt. In the present investigation, we studied the
      conformational flexibility of MtbICL to better understand its stability and
      catalytic activity. Our biochemical results showed that a point mutation at
      Phe345, which is topologically distant (>10 A) to the active site signature
      sequence (189KKCGH193), completely abolishes the activity of the enzyme. In depth
      computational analyses were carried out for understanding the structural
      alterations using molecular dynamics, time-dependent secondary structure and
      principal component analysis. The results showed that the mutated residue
      increased the structural flexibility and induced conformational changes near the
      active site (residues 170-210) and in the C-terminal lid region (residues 411
      428). Both these regions are involved in the catalytic activity of MtbICL. Upon
      mutation, the residual mobility of the enzyme increased, resulting in a decrease
      in the stability, which was confirmed by the lower free energy of stabilization
      in the mutant enzyme suggesting the destabilization in the structure. Our results
      have both biological importance and chemical novelty. It reveals internal
      dynamics of the enzyme structure and also suggests that regions other than the
      active site should be exploited for targeting MtbICL inhibition and development
      of novel anti-tuberculosis compounds.

PMID- 28432346
TI  - Functionally interchangeable cis-acting RNA elements in both genome segments of a
      picorna-like plant virus.
AB  - Cis-acting RNA structures in the genomes of RNA viruses play critical roles in
      viral infection, yet their importance in the bipartite genomes of the picorna
      like, plant-infecting comoviruses has not been carefully investigated. We
      previously characterized SLC, a stem-loop structure in the 5' untranslated region
      (UTR) of the bean pod mottle comovirus (BPMV) RNA2, and found it to be essential
      for RNA2 accumulation in infected cells. Here we report the identification of
      SL1, a similar cis-acting element in the other BPMV genome segment - RNA1. SL1
      encompasses a portion of RNA1 5' UTR but extends into the coding sequence for
      nine nucleotides, thus was missed in the previous study. While the stems of SL1
      and SLC share little sequence similarity, their end loops are of the same size
      and identical for 11 of 15 nucleotides. Importantly, SL1 and SLC are functionally
      interchangeable, and separate exchanges of the stem and loop portions were
      likewise well tolerated. By contrast, the conserved loop sequence tolerated
      minimal perturbations. Finally, stem-loop structures with similar configurations
      were identified in two other comoviruses. Therefore, SL1 and SLC are likely
      essential comoviral RNA structures that play a conserved function in viral
      infection cycles.

PMID- 28432347
TI  - Identification and Characterization of Differentially-Regulated Type IVb Pilin
      Genes Necessary for Predation in Obligate Bacterial Predators.
AB  - Bdellovibrio bacteriovorus is an obligate predator of bacteria that grows and
      divides within the periplasm of its prey. Functions involved in the early steps
      of predation have been identified and characterized, but mediators of prey
      invasion are still poorly detailed. By combining omics data available for
      Bdellovibrio and like organisms (BALO's), we identified 43 genes expressed in B.
      bacteriovorus during the early interaction with prey. These included genes in a
      tight adherence (TAD) operon encoding for two type IVb fimbriae-like pilin
      proteins (flp1 and flp2), and their processing and export machinery. Two
      additional flp genes (flp3 and flp4) were computationally identified at other
      locations along the chromosome, defining the largest and most diverse type IVb
      complement known in bacteria to date. Only flp1, flp2 and flp4 were expressed;
      their respective gene knock-outs resulted in a complete loss of the predatory
      ability without losing the ability to adhere to prey cells. Additionally, we
      further demonstrate differential regulation of the flp genes as the TAD operon of
      BALOs with different predatory strategies is controlled by a flagellar sigma
      factor FliA, while flp4 is not. Finally, we show that FliA, a known flagellar
      transcriptional regulator in other bacteria, is an essential Bdellovibrio gene.

PMID- 28432348
TI  - White spot syndrome virus VP28 specific double-stranded RNA provides protection
      through a highly focused siRNA population.
AB  - Several studies have demonstrated that injection of double-stranded RNAs (dsRNA)
      homologous to mRNA for the white spot syndrome virus (WSSV) viral protein 28
      (VP28) can induce protection in shrimp against WSSV through RNA interference
      (RNAi). In comparison to shrimp injected with either PBS or a green fluorescent
      protein (GFP) nonspecific dsRNA, we obtained nearly complete protection against
      WSSV infection in shrimp injected with VP28 dsRNA. Upregulation of host genes
      associated with small RNA silencing was measured 48 hours post treatment in
      groups injected with dsRNA, and although the VP28-treated group remained
      moderately upregulated after challenge with WSSV, many-fold higher induction was
      observed in both control groups reflecting the ongoing viral infection. RNA
      sequencing of VP28-treated shrimp demonstrated a siRNA population dominated by
      high levels of 22 nt long molecules narrowly targeting the VP28 mRNA both before
      and after challenge with WSSV. Conversely, while no siRNAs targeting WSSV were
      detected before challenge, a broad response of 22 nt siRNAs mapping across the
      entire WSSV genome were found in both control groups after challenge. These
      results give detailed insight to how dsRNA targeting VP28 function to induce
      protection against WSSV, by generating a highly focused population of 22 nt long
      siRNA molecules.

PMID- 28432349
TI  - Augmentation of working memory training by transcranial direct current
      stimulation (tDCS).
AB  - Transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal
      cortex (dlPFC) can modulate working memory (WM) performance. However, evidence
      regarding the enhancement of WM training, its sustainability and transferability
      is ambiguous. Since WM functioning appears to be lateralized in respect to
      stimulus characteristics, this study examined the difference between task
      congruent (spatial-right, verbal-left), task-incongruent (spatial-left, verbal
      right) and sham tDCS in regards to the efficacy of WM training. In a randomized,
      sham-controlled experiment, 71 healthy adults trained on a spatial or verbal
      adaptive n-back task. After a baseline session, anodal or sham tDCS (1 mA) to the
      right or left dlPFC was applied during the next three training sessions.
      Sustainability of training gains and near-transfer (verbal or spatial 3-back
      task) were tested in a fourth training and a follow-up session. Compared to sham
      stimulation, we found a steeper learning curve when WM training was combined with
      task-congruent tDCS. This advantage was also present compared to task-incongruent
      tDCS. Moreover, these effects lasted for up to nine months and transferred to the
      respective untrained task. These long-lasting, transferable, task-specific
      effects demonstrate a behaviorally relevant and sustainable facilitation of
      neuroplastic processes by tDCS that could be harnessed for the treatment of
      disorders associated with deficient WM.

PMID- 28432350
TI  - Enhancing the throughput and multiplexing capabilities of next generation
      sequencing for efficient implementation of pooled shRNA and CRISPR screens.
AB  - Next generation sequencing is becoming the method of choice for functional
      genomic studies that use pooled shRNA or CRISPR libraries. A key challenge in
      sequencing these mixed-oligo libraries is that they are highly susceptible to
      hairpin and/or heteroduplex formation. This results in polyclonal, low quality,
      and incomplete reads and reduces sequencing throughput. Unfortunately, this
      challenge is significantly magnified in low-to-medium throughput bench-top
      sequencers as failed reads significantly perturb the maximization of sequence
      coverage and multiplexing capabilities. Here, we report a methodology that can be
      adapted to maximize the coverage on a bench-top, Ion PGM System for smaller shRNA
      libraries with high efficiency. This ligation-based, half-shRNA sequencing
      strategy minimizes failed sequences and is also equally amenable to high
      throughput sequencers for increased multiplexing. Towards this, we also
      demonstrate that our strategy to reduce heteroduplex formation improves
      multiplexing capabilities of pooled CRISPR screens using Illumina NextSeq 500.
      Overall, our method will facilitate sequencing of pooled shRNA or CRISPR
      libraries from genomic DNA and maximize sequence coverage.

PMID- 28432351
TI  - Early measurement of IL-10 predicts the outcomes of patients with acute
      respiratory distress syndrome receiving extracorporeal membrane oxygenation.
AB  - Patients diagnosed with acute respiratory distress syndrome are generally
      severely distressed and associated with high morbidity and mortality despite
      aggressive treatments such as extracorporeal membrane oxygenation (ECMO) support.
      To identify potential biomarker of predicting value for appropriate use of this
      intensive care resource, plasma interleukin-10 along with relevant inflammatory
      cytokines and immune cell populations were examined during the early and
      subsequent disease courses of 51 critically ill patients who received ECMO
      support. High interleukin-10 levels at the time of ECMO installation and during
      the first 6 hours after ECMO support of these patients stand as a promising
      biomarker associated with grave prognosis. The initial interleukin-10 level is
      correlated to other conventional risk evaluation scores as a predictive factor
      for survival, and furthermore, elevated interleukin-10 levels are also related to
      a delayed recovery of certain immune cell populations such as CD14+CD16+,
      CD14+TLR4+ monocytes, and T regulator cells. Genetically, high interleukin-10 is
      associated to two polymorphic nucleotides (-592 C and -819 C) at the interleukin
      10 gene promoter area. Our finding provides prognostic and mechanistic
      information on the outcome of severely respiratory distressed patients, and
      potentially paves the strategy to develop new therapeutic modality based on the
      principles of precision medicine.

PMID- 28432352
TI  - Low-cost, Low-bias and Low-input RNA-seq with High Experimental Verifiability
      based on Semiconductor Sequencing.
AB  - Low-input RNA-seq is powerful to represent the gene expression profiles with
      limited number of cells, especially when single-cell variations are not the aim.
      However, pre-amplification-based and molecule index-based library construction
      methods boost bias or require higher throughput. Here we demonstrate a simple,
      low-cost, low-bias and low-input RNA-seq with ion torrent semiconductor
      sequencing (LIEA RNA-seq). We also developed highly accurate and error-tolerant
      spliced mapping algorithm FANSe2splice to accurately map the single-ended reads
      to the reference genome with better experimental verifiability than the previous
      spliced mappers. Combining the experimental and computational advancements, our
      solution is comparable with the bulk mRNA-seq in quantification, reliably detects
      splice junctions and minimizes the bias with much less mappable reads.

PMID- 28432353
TI  - Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice
      after moderate noise exposure.
AB  - Noise induced hearing loss (NIHL) is a disease that affects millions of
      Americans. Identifying genetic pathways that influence recovery from noise
      exposure is an important step forward in understanding NIHL. The transcription
      factor Foxo3 integrates the cellular response to oxidative stress and plays a
      role in extending lifespan in many organisms, including humans. Here we show that
      Foxo3 is required for auditory function after noise exposure in a mouse model
      system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the
      middle and higher frequencies. SEM reveals persistent damage to some surviving
      outer hair cell stereocilia. However, DPOAE analysis reveals that some function
      is preserved in low frequency outer hair cells, despite concomitant profound
      hearing loss. Inner hair cells, auditory synapses and spiral ganglion neurons are
      all present after noise exposure in the Foxo3KO/KO fourteen days post noise
      (DPN). We also report anti-Foxo3 immunofluorescence in adult human outer hair
      cells. Taken together, these data implicate Foxo3 and its transcriptional targets
      in outer hair cell survival after noise damage. An additional role for Foxo3 in
      preserving hearing is likely, as low frequency auditory function is absent in
      noise exposed Foxo3KO/KOs even though all cells and structures are present.

PMID- 28432354
TI  - Structural and functional analysis of lysozyme after treatment with dielectric
      barrier discharge plasma and atmospheric pressure plasma jet.
AB  - The variation in the biological function of proteins plays an important role in
      plasma medicine and sterilization. Several non-thermal plasma sources with
      different feeding gases are used worldwide for plasma treatment, including
      dielectric barrier discharge (DBD) and atmospheric-pressure plasma jet (APPJ) as
      the most commonly used sources. Therefore, in the present work, we used both DBD
      and APPJ plasma sources with N2 and air as feeding gases to evaluate the effects
      on the structural, thermodynamic, and activity changes of enzymes. In the current
      work, we used lysozyme as a model enzyme and verified the structural changes
      using circular dichroism (CD), fluorescence, and X-ray crystallography. In
      addition, we investigated the lysozyme thermodynamics using CD thermal analysis
      and changes in the B-factor from X-ray crystallography. The results showed that
      lysozyme activity decreased after the plasma treatment. From these analyses, we
      concluded that N2-feeding gas plasma disturbs the structure and activity of
      lysozyme more than Air feeding gas plasma in our experimental studies. This study
      provides novel fundamental information on the changes to enzymes upon plasma
      treatment, which has been absent from the literature until now.

PMID- 28432355
TI  - Basal autophagy prevents autoactivation or enhancement of inflammatory signals by
      targeting monomeric MyD88.
AB  - Autophagy, the processes of delivery of intracellular components to lysosomes,
      regulates induction of inflammation. Inducible macroautophagy degrades
      inflammasomes and dysfunctional mitochondria to downregulate inflammatory
      signals. Nonetheless, the effects of constitutive basal autophagy on inflammatory
      signals are largely unknown. Here, we report a previously unknown effect of basal
      autophagy. Lysosomal inhibition induced weak inflammatory signals in the absence
      of a cellular stimulus and in the presence of a nutrient supply, and their
      induction was impaired by MyD88 deficiency. During lysosomal inhibition, MyD88
      was accumulated, and overabundant MyD88 autoactivated downstream signaling or
      enhanced TLR/IL-1R-mediated signaling. MyD88 is probably degraded via basal
      microautophagy because macroautophagy inhibitors, ATG5 deficiency, and an
      activator of chaperone-mediated autophagy did not affect MyD88. Analysis using a
      chimeric protein whose monomerization/dimerization can be switched revealed that
      monomeric MyD88 is susceptible to degradation. Immunoprecipitation of monomeric
      MyD88 revealed its interaction with TRAF6. In TRAF6-deficient cells, degradation
      of basal MyD88 was enhanced, suggesting that TRAF6 participates in protection
      from basal autophagy. Thus, basal autophagy lowers monomeric MyD88 expression,
      and thereby autoactivation of inflammatory signals is prevented. Given that
      impairment of lysosomes occurs in various settings, our results provide novel
      insights into the etiology of inflammatory signals that affect consequences of
      inflammation.

PMID- 28432356
TI  - A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of
      double-strand breaks.
AB  - DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity
      preservation. Defective DDR causes accumulation of deleterious mutations and DNA
      lesions that can lead to genomic instabilities and carcinogenesis. Identifying
      new players in the DDR, therefore, is essential to advance the understanding of
      the molecular mechanisms by which cells keep their genetic material intact. Here,
      we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex
      are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs
      double-strand break (DSB) repair by homology-directed repair (HDR), but has no
      deleterious effect on the integrity of non-homologous end joining. We also
      demonstrate that Rpp29 and Rpp21, but not Rpp14, Rpp25 and Rpp38, are rapidly and
      transiently recruited to laser-microirradiated sites. Rpp29 and Rpp21 bind poly
      ADP-ribose moieties and are recruited to DNA damage sites in a PARP1-dependent
      manner. Remarkably, depletion of the catalytic H1 RNA subunit diminishes their
      recruitment to laser-microirradiated regions. Moreover, RNase P activity is
      augmented after DNA damage in a PARP1-dependent manner. Altogether, our results
      describe a previously unrecognized function of the RNase P subunits, Rpp29 and
      Rpp21, in fine-tuning HDR of DSBs.

PMID- 28432358
TI  - Differential sensitivity to infections and antimicrobial peptide-mediated immune
      response in four silkworm strains with different geographical origin.
AB  - The domesticated silkworm Bombyx mori has an innate immune system, whose main
      effectors are the antimicrobial peptides (AMPs). Silkworm strains are commonly
      grouped into four geographical types (Japanese, Chinese, European and Tropical)
      and are generally characterised by a variable susceptibility to infections. To
      clarify the genetic and molecular mechanisms on which the different responses to
      infections are based, we exposed one silkworm strain for each geographical area
      to oral infections with the silkworm pathogens Enterococcus mundtii or Serratia
      marcescens. We detected a differential susceptibility to both bacteria, with the
      European strain displaying the lowest sensitivity to E. mundtii and the Indian
      one to S. marcescens. We found that all the strains were able to activate the AMP
      response against E. mundtii. However, the highest tolerance of the European
      strain appeared to be related to the specific composition of its AMP cocktail,
      containing more effective variants such as a peculiar Cecropin B6 isoform. The
      resistance of the Indian strain to S. marcescens seemed to be associated with its
      prompt capability to activate the systemic transcription of AMPs. These data
      suggest that B. mori strains with distinct genetic backgrounds employ different
      strategies to counteract bacterial infections, whose efficacy appears to be
      pathogen-dependent.

PMID- 28432357
TI  - In-Silico Drug discovery approach targeting receptor tyrosine kinase-like orphan
      receptor 1 for cancer treatment.
AB  - Receptor tyrosine kinases (RTK) are important cell signaling molecules that
      influence many cellular processes. Receptor tyrosine kinase such as orphan
      receptor 1 (Ror1), a surface antigen, is a member of the RTK family of Ror, which
      plays a crucial role in cancers that have high-grade histology. As Ror1 has been
      implicated to be a potential target for cancer therapy, we selected this protein
      for further investigation. The secondary and tertiary structure of this protein
      was determined, which revealed that this protein contained three beta-sheets,
      seven alpha-helices, and coils. The prediction of the active site revealed its
      cage-like function that opens for ligand entry and then closes for interacting
      with the ligands. Optimized ligands from the database were virtually screened to
      obtain the most efficient and potent ones. The screened ligands were evaluated
      for their therapeutic usefulness. Furthermore, the ligands that passed the test
      were docked to the target protein resulting in a few ligands with high score,
      which were analyzed further. The highest scoring ligand, Beta-1, 2,3,4,6-Penta-O
      Galloyl-D-Glucopyranose was reported to be a naturally occurring tannin. This in
      silico approach indicates the potential of this molecule for advancing a further
      step in cancer treatment.

PMID- 28432360
TI  - Functional ectopic neuritogenesis by retinal rod bipolar cells is regulated by
      miR-125b-5p during retinal remodeling in RCS rats.
AB  - Following retinal degeneration, retinal remodeling can cause neuronal
      microcircuits to undergo structural alterations, which particularly affect the
      dendrites of bipolar cells. However, the mechanisms and functional consequences
      of such changes remain unclear. Here, we used Royal College of Surgeon (RCS) rats
      as a model of retinal degeneration, to study structural changes in rod bipolar
      cells (RBCs) and the underlying mechanisms of these changes. We found that, with
      retinal degeneration, RBC dendrites extended into the outer nuclear layer (ONL)
      of the retina, and the ectopic dendrites formed synapses with the remaining
      photoreceptors. This ectopic neuritogenesis was associated with brain-derived
      neurotrophic factor (BDNF) - expression of which was negatively regulated by miR
      125b-5p. Overexpression of miR-125b-5p in the retinae of RCS rats diminished RBC
      ectopic dendrites, and compromised the b-wave of the flash electroretinogram
      (ERG). In contrast, down-regulation of miR-125b-5p (or exogenous BDNF treatment)
      increased RBC ectopic dendrites, and improved b-wave. Furthermore, we showed that
      the regulation of ectopic neuritogenesis by BDNF occurred via the downstream
      modulation of the TrkB-CREB signaling pathway. Based on these findings, we
      conclude that ectopic dendrites are likely to be providing functional benefits
      and that, in RCS rats, miR-125b-5p regulates ectopic neuritogenesis by RBCs
      through modulation of the BDNF-TrkB-CREB pathway. This suggests that therapies
      that reduce miR-125b-5p expression could be beneficial in human retinal
      degenerative disease.

PMID- 28432359
TI  - Role of the Ion Channel Extracellular Collar in AMPA Receptor Gating.
AB  - AMPA subtype ionotropic glutamate receptors mediate fast excitatory
      neurotransmission and are implicated in numerous neurological diseases. Ionic
      currents through AMPA receptor channels can be allosterically regulated via
      different sites on the receptor protein. We used site-directed mutagenesis and
      patch-clamp recordings to probe the ion channel extracellular collar, the binding
      region for noncompetitive allosteric inhibitors. We found position and
      substitution-dependent effects for introduced mutations at this region on AMPA
      receptor gating. The results of mutagenesis suggested that the transmembrane
      domains M1, M3 and M4, which contribute to the ion channel extracellular collar,
      undergo significant relative displacement during gating. We used molecular
      dynamics simulations to predict an AMPA receptor open state structure and
      rationalize the results of mutagenesis. We conclude that the ion channel
      extracellular collar plays a distinct role in gating and represents a hub for
      powerful allosteric modulation of AMPA receptor function that can be used for
      developing novel therapeutics.

PMID- 28432361
TI  - Disease biomarker identification from gene network modules for metastasized
      breast cancer.
AB  - Advancement in science has tended to improve treatment of fatal diseases such as
      cancer. A major concern in the area is the spread of cancerous cells, technically
      refered to as metastasis into other organs beyond the primary organ. Treatment in
      such a stage of cancer is extremely difficult and usually palliative only. In
      this study, we focus on finding gene-gene network modules which are functionally
      similar in nature in the case of breast cancer. These modules extracted during
      the disease progression stages are analyzed using p-value and their associated
      pathways. We also explore interesting patterns associated with the causal genes,
      viz., SCGB1D2, MET, CYP1B1 and MMP9 in terms of expression similarity and pathway
      contexts. We analyze the genes involved in both the stages- non metastasis and
      metastatsis and change in their expression values, their associated pathways and
      roles as the disease progresses from one stage to another. We discover three
      additional pathways viz., Glycerophospholipid metablism, h-Efp pathway and CARM1
      and Regulation of Estrogen Receptor, which can be related to the metastasis phase
      of breast cancer. These new pathways can be further explored to identify their
      relevance during the progression of the disease.

PMID- 28432362
TI  - Succinate supplementation improves metabolic performance of mixed glial cell
      cultures with mitochondrial dysfunction.
AB  - Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels
      and oxygen, contributes to pathological changes following traumatic spinal cord
      or traumatic brain injury (TBI). In the present study, we tested the hypothesis
      that succinate supplementation can improve cellular energy state under
      metabolically stressed conditions in a robust, reductionist in vitro model of
      mitochondrial dysfunction in which primary mixed glial cultures (astrocytes,
      microglia and oligodendrocytes) were exposed to the mitochondrial complex I
      inhibitor rotenone. Cellular response was determined by measuring intracellular
      ATP, extracellular metabolites (glucose, lactate, pyruvate), and oxygen
      consumption rate (OCR). Rotenone produced no significant changes in glial ATP
      levels. However, it induced metabolic deficits as evidenced by lactate/pyruvate
      ratio (LPR) elevation (a clinically-established biomarker for poor outcome in
      TBI) and decrease in OCR. Succinate addition partially ameliorated these
      metabolic deficits. We conclude that succinate can improve glial oxidative
      metabolism, consistent our previous findings in TBI patients' brains. The mixed
      glial cellular model may be useful in developing therapeutic strategies for
      conditions involving mitochondrial dysfunction, such as TBI.

PMID- 28432363
TI  - Joint-based description of protein structure: its application to the geometric
      characterization of membrane proteins.
AB  - A macroscopic description of a protein structure allows an understanding of the
      protein conformations in a more simplistic manner. Here, a new macroscopic
      approach that utilizes the joints of the protein secondary structures as a basic
      descriptor for the protein structure is proposed and applied to study the
      arrangement of secondary structures in helical membrane proteins. Two types of
      dihedral angle, Omega and lambda, were defined based on the joint points of the
      transmembrane (TM) helices and loops, and employed to analyze 103 non-homologous
      membrane proteins with 3 to 14 TM helices. The Omega-lambda plot, which is a
      distribution plot of the dihedral angles of the joint points, identified the
      allowed and disallowed regions of helical arrangement. Analyses of consecutive
      dihedral angle patterns indicated that there are preferred patterns in the
      helical alignment and extension of TM proteins, and helical extension pattern in
      TM proteins is varied as the size of TM proteins increases. Finally, we could
      identify some symmetric protein pairs in TM proteins under the joint-based
      coordinate and 3-dimensional coordinates. The joint-based approach is expected to
      help better understand and model the overall conformational features of
      complicated large-scale proteins, such as membrane proteins.

PMID- 28432364
TI  - RRM domain of ALS/FTD-causing FUS characteristic of irreversible unfolding
      spontaneously self-assembles into amyloid fibrils.
AB  - 526-residue FUS functions to self-assemble into reversible droplets/hydrogels,
      which could be further solidified into pathological fibrils. FUS is intrinsically
      prone to aggregation, composed of N-terminal low-sequence complexity (LC); RNA
      recognition motif (RRM) and C-terminal LC domains. Intriguingly, previous in vivo
      studies revealed that its RRM is required for manifesting FUS cytotoxicity but
      the underlying mechanism remains unknown. Here, we characterized solution
      conformations of FUS and its five differentially dissected fragments, followed by
      detailed investigations on thermal unfolding, NMR dynamics and self-assembly of
      RRM. The results decipher: (1) the N- and C-terminal LC domains are intrinsically
      disordered, while RRM is folded. Intriguingly, well-dispersed HSQC peaks of RRM
      disappear in the full-length FUS, reminiscent of the previous observation on TDP
      43. (2) FUS RRM is characteristic of irreversible unfolding. "Model-free"
      analysis of NMR relaxation data decodes that RRM has high ps-ns conformational
      dynamics even over some residues within secondary structure regions. (3) RRM
      spontaneously self-assembles into amyloid fibrils. Therefore, in addition to the
      well-established prion-like region, FUS RRM is also prone to self-assembly to
      form amyloid fibrils. Taken together, FUS RRM appears to play a crucial role in
      exaggerating the physiological/reversible self-assembly into
      pathological/irreversible fibrillization, thus contributing to manifestation of
      FUS cytotoxicity.

PMID- 28432365
TI  - Effects of porosity on dynamic indentation resistance of silica nanofoam.
AB  - The dynamic indentation behaviors of monolithic silica nanofoams of various
      porosities are investigated. When the pore size is on the nm scale, as the
      porosity increases, despite the decrease in mass density, the resistance offered
      by silica nanofoam to dynamic indentation is maintained at a high level, higher
      than the resistance of solid silica or regular porous silica. This phenomenon is
      related to the fast collapse of nanocells, which produces a locally hardened
      region and significantly increases the volume of material involved in impact
      energy dissipation.

PMID- 28432366
TI  - Exploring quantum Griffiths phase in Ni1-x V x nanoalloys.
AB  - Metallic Ni1-x V x alloys exhibit a ferromagnetic to paramagnetic disordered
      quantum phase transition in bulk. Such a phase transition is accompanied by a
      quantum Griffiths phase (QGP), featuring fractional power-law temperature
      dependences of physical variables, like magnetic susceptibility and specific
      heat, at low temperatures. As nanoparticles (NP's) usually exhibit properties
      significantly different from their bulk counterparts, it is intriguing to explore
      the occurrence of quantum Griffiths phase in Ni1-x V x nanoalloys. NP's of Ni1-x
      V x (0 <= x <= 0.17) alloys are prepared by a chemical reflux method. The
      structure and composition of the nanoalloys are determined by X-ray diffraction,
      X-ray photoelectron spectroscopy and electron microscopy techniques. Metallicity
      of the samples has been ensured by electrical resistivity measurements. DC
      magnetization results suggest that ferromagnetism persists in the NP's until x =
      0.17. Low-temperature upturns in magnetic susceptibility and heat capacity hint
      at critical fluctuations evolving with V-doping. The fluctuations might stem from
      isolated Ni-clusters within the ferromagnetic NP, indicating a QGP region ranging
      from x = 0.085 to x ? 0.17.

PMID- 28432367
TI  - Predatory or Legitimate Journals.

PMID- 28432368
TI  - Indoor Radon in Micro-geological Setting of an Indigenous Community in Canada: A
      Pilot Study for Hazard Identification.
AB  - BACKGROUND: Radon is the second leading cause of lung cancer after smoking. In
      Canada, the health authorities have no access to comprehensive profile of the
      communities built over uranium-rich micro-geological settings. The present indoor
      radon monitoring guideline is unable to provide an accurate identification of
      health hazards due to discounting several parameters of housing characteristics.
      OBJECTIVE: To explore indoor radon levels in a micro-geological setting known for
      high uranium in bedrock and to develop a theoretical model for a revised radon
      testing protocol. METHODS: We surveyed a remote Inuit community in Labrador,
      located in the midst of uranium belt. We selected 25 houses by convenience
      sampling and placed electret-ion-chamber radon monitoring devices in the lowest
      levels of the house (basement/crawl space). The standard radon study
      questionnaire developed and used by Health Canada was used. RESULTS: 7 (28%)
      houses had radon levels above the guideline value (range 249 to 574 Bq/m3).
      Housing characteristics, such as floors, sump holes, ventilation, and heating
      systems were suspected for high indoor radon levels and health consequences.
      CONCLUSION: There is a possibility of the existence of high-risk community in a
      low-risk region. The regional and provincial health authorities would be
      benefited by consulting geologists to identify potentially high-risk communities
      across the country. Placing testing devices in the lowest levels provides more
      accurate assessment of indoor radon level. The proposed protocol, based on
      synchronized testing of radon (at the lowest level of houses and in rooms of
      normal occupancy) and thorough inspection of the houses will be a more effective
      lung cancer prevention strategy.

PMID- 28432370
TI  - The Threshold Temperature and Lag Effects on Daily Excess Mortality in Harbin,
      China: A Time Series Analysis.
AB  - BACKGROUND: A large number of studies have reported the relationship between
      ambient temperature and mortality. However, few studies have focused on the
      effects of high temperatures on cardio-cerebrovascular diseases mortality (CCVDM)
      and their acute events (ACCVDM). OBJECTIVE: To assess the threshold temperature
      and time lag effects on daily excess mortality in Harbin, China. METHODS: A
      generalized additive model (GAM) with a Poisson distribution was used to
      investigate the relative risk of mortality for each 1  degrees C increase above
      the threshold temperature and their time lag effects in Harbin, China. RESULTS:
      High temperature threshold was 26  degrees C in Harbin. Heat effects were
      immediate and lasted for 0-6 and 0-4 days for CCVDM and ACCVDM, respectively. The
      acute cardiovascular disease mortality (ACVDM) seemed to be more sensitive to
      temperature than cardiovascular disease mortality (CVDM) with higher death risk
      and shorter time lag effects. The lag effects lasted longer for cerebrovascular
      disease mortality (CBDM) than CVDM; so did ACBDM compared to ACVDM. CONCLUSION:
      Hot temperatures increased CCVDM and ACCVDM in Harbin, China. Public health
      intervention strategies for hot temperatures adaptation should be concerned.

PMID- 28432369
TI  - Sensitivity to Antibiotics of Bacteria Exposed to Gamma Radiation Emitted from
      Hot Soils of the High Background Radiation Areas of Ramsar, Northern Iran.
AB  - BACKGROUND: Over the past several years our laboratories have investigated
      different aspects of the challenging issue of the alterations in bacterial
      susceptibility to antibiotics induced by physical stresses. OBJECTIVE: To explore
      the bacterial susceptibility to antibiotics in samples of Salmonella enterica
      subsp. enterica serovar Typhimurium (S. typhimurium), Staphylococcus aureus, and
      Klebsiella pneumoniae after exposure to gamma radiation emitted from the soil
      samples taken from the high background radiation areas of Ramsar, northern Iran.
      METHODS: Standard Kirby-Bauer test, which evaluates the size of the zone of
      inhibition as an indicator of the susceptibility of different bacteria to
      antibiotics, was used in this study. RESULTS: The maximum alteration of the
      diameter of inhibition zone was found for K. pneumoniae when tested for
      ciprofloxacin. In this case, the mean diameter of no growth zone in non
      irradiated control samples of K. pneumoniae was 20.3 (SD 0.6) mm; it was 14.7 (SD
      0.6) mm in irradiated samples. On the other hand, the minimum changes in the
      diameter of inhibition zone were found for S. typhimurium and S. aureus when
      these bacteria were tested for nitrofurantoin and cephalexin, respectively.
      CONCLUSION: Gamma rays were capable of making significant alterations in
      bacterial susceptibility to antibiotics. It can be hypothesized that high levels
      of natural background radiation can induce adaptive phenomena that help
      microorganisms better cope with lethal effects of antibiotics.

PMID- 28432371
TI  - Impact of Diabetes Mellitus on Occupational Health Outcomes in Canada.
AB  - BACKGROUND: Research suggests that diabetes mellitus (DM) has a negative impact
      on employment and workplace injury, but there is little data within the Canadian
      context. OBJECTIVE: To determine if DM has an impact on various occupational
      health outcomes using the Canadian Community Health Survey (CCHS). METHODS: CCHS
      data between 2001 and 2014 were used to assess the relationships between DM and
      various occupational health outcomes. The final sample size for the 14-year study
      period was 505 606, which represented 159 432 239 employed Canadians aged 15-75
      years during this period. RESULTS: We found significant associations between
      people with diabetes and their type of occupation (business, finance,
      administration: 2009, p=0.002; 2010, p=0.002; trades, transportation, equipment:
      2008, p=0.025; 2011, p=0.002; primary industry, processing, manufacturing,
      utility: 2013, p=0.018), reasons for missing work (looking for work: 2001,
      p=0.024; school or education: 2003, p=0.04; family responsibilities: 2014,
      p=0.015; other reasons: 2001, p<0.001; 2003, p<0.001; 2010, p=0.015), the number
      of work days missed (2010, 3 days, p=0.033; 4 days, p=0.038; 11 days, p<0.001; 24
      days, p<0.001), and work-related injuries (traveling to and from work: 2014,
      p=0.003; working at a job or business: 2009, p=0.021; 2014, p=0.001). CONCLUSION:
      DM is associated with various occupational health outcomes, including work
      related injury, work loss productivity, and occupation type. This allows
      stakeholders to assess the impact of DM on health outcomes in workplace.

PMID- 28432372
TI  - Evaluation of the Auditory Pathway in Traffic Policemen.
AB  - BACKGROUND: Traffic policemen working at heavy traffic junctions are continuously
      exposed to high level of noise and its health consequences. OBJECTIVE: To assess
      the hearing pathway in traffic policemen by means of brainstem evoked response
      audiometry (BERA), mid-latency response (MLR), and slow vertex response (SVR).
      METHODS: In this observational comparative study, BERA, MLR, and SVR were tested
      in 35 male traffic policemen with field posting of more than 3 years. 35 age
      matched men working in our college served as controls. RESULTS: Increase in the
      latencies of waves I and III of BERA, and IPL I-III were observed. Compared to
      controls, the MLR and SVR waves showed no significant changes in studied
      policemen. CONCLUSION: We found that chronic exposure of traffic policemen to
      noise resulted in delayed conduction in peripheral part of the auditory pathway,
      ie, auditory nerve up to the level of superior olivary nucleus; no impairment was
      observed at the level of sub-cortical, cortical, or the association areas.

PMID- 28432373
TI  - Identifying Predatory or Pseudo-Journals.

PMID- 28432374
TI  - Bacterial Endotoxins and their Impact on Respiratory System among Greek Cotton
      Industry Workers.

PMID- 28432375
TI  - Occupational Cutaneous Burn.

PMID- 28432376
TI  - MDMA does not alter responses to the Trier Social Stress Test in humans.
AB  - RATIONALE: +/-3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a stimulant
      psychedelic drug with unique social effects. It may dampen reactivity to negative
      social stimuli such as social threat and rejection. Perhaps because of these
      effects, MDMA has shown promise as a treatment for post-traumatic stress disorder
      (PTSD). However, the effect of single doses of MDMA on responses to an acute
      psychosocial stressor has not been tested. OBJECTIVES: In this study, we sought
      to test the effects of MDMA on responses to stress in healthy adults using a
      public speaking task. We hypothesized that the drug would reduce responses to the
      stressful task. METHODS: Volunteers (N = 39) were randomly assigned to receive
      placebo (N = 13), 0.5 mg/kg MDMA (N = 13), or 1.0 mg/kg MDMA (N = 13) during a
      stress and a no-stress session. Dependent measures included subjective reports of
      drug effects and emotional responses to the task, as well as salivary cortisol,
      heart rate, and blood pressure. RESULTS: The stress task produced its expected
      increase in physiological responses (cortisol, heart rate) and subjective ratings
      of stress in all three groups, and MDMA produced its expected subjective and
      physiological effects. MDMA alone increased ratings of subjective stress, heart
      rate, and saliva cortisol concentrations, but contrary to our hypothesis, it did
      not moderate responses to the Trier Social Stress Test. CONCLUSIONS: Despite its
      efficacy in PTSD and anxiety, MDMA did not reduce either the subjective or
      objective responses to stress in this controlled study. The conditions under
      which MDMA relieves responses to negative events or memories remain to be
      determined.

PMID- 28432377
TI  - Emerging roles of calpain proteolytic systems in macrophage cholesterol handling.
AB  - Calpains are Ca2+-dependent intracellular proteases that play central roles in
      the post-translational processing of functional proteins. In mammals, calpain
      proteolytic systems comprise the endogenous inhibitor calpastatin as well as 15
      homologues of the catalytic subunits and two homologues of the regulatory
      subunits. Recent pharmacological and gene targeting studies in experimental
      animal models have revealed the contribution of conventional calpains, which
      consist of the calpain-1 and -2 isozymes, to atherosclerotic diseases. During
      atherogenesis, conventional calpains facilitate the CD36-dependent uptake of
      oxidized low-density lipoprotein (LDL), and block cholesterol efflux through ATP
      binding cassette transporters in lesional macrophages, allowing the expansion of
      lipid-enriched atherosclerotic plaques. In addition, calpain-6, an unconventional
      non-proteolytic calpain, in macrophages reportedly potentiates pinocytotic uptake
      of native LDL, and attenuates the efferocytic clearance of apoptotic and necrotic
      cell corpses from the lesions. Herein, we discuss the recent progress that has
      been made in our understanding of how calpain contributes to atherosclerosis, in
      particular focusing on macrophage cholesterol handling.

PMID- 28432379
TI  - High-Resolution Tomography-Based Quantification of Cortical Porosity and Cortical
      Thickness at the Surgical Neck of the Humerus During Aging.
AB  - Fractures of the proximal humerus are highly related to age and osteoporotic bone
      remodeling. Previous studies have highlighted the cortex as a major side of the
      bone loss, but the microstructural changes of the humerus have not been evaluated
      entirely. Sixty-four (n = 64) humeri of a representative collective (18-100
      years) were scanned with high-resolution peripheral quantitative computed
      tomography (82 um). Bone mineral density (BMD), trabecular bone volume fraction
      (Tb.BV/TV), cortical thickness (Ct.Th), and cortical porosity (Ct.Po) were
      determined with respect to four age groups. The BMD (r = -0.42), Ct.Th (r =
      0.57), and Tb.BV/TV (r = 0.68) showed an age group-related decrease, while the
      Ct.Po increased (r = -0.55). The oldest group (80-100 years) revealed an
      extensively higher Ct.Po of +87% compared to the youngest group (18-44 years),
      while the Ct.Th and Tb.BV/TV were significantly lower by -35 and -49% (p < 0.05).
      The main cortical bone loss occurred after 65 years with the Ct.Th (-34%) and
      Tb.BV/TV (-40%) being clearly lower and the Ct.Po (+93%) clearly higher compared
      to the youngest group. In summary, osteoporosis leads to an age-related higher
      Ct.Po and reduced Ct.Th at the humeral cortex of the surgical neck. The bone loss
      of the cortex predominantly occurs around the age of 65 years and is very likely
      to reduce the mechanical strength and highly increases the fracture risk.

PMID- 28432378
TI  - Advances in anti-viral immune defence: revealing the importance of the IFN
      JAK/STAT pathway.
AB  - Interferon-alpha (IFN-alpha) is a potent anti-viral cytokine, critical to the
      host immune response against viruses. IFN-alpha is first produced upon viral
      detection by pathogen recognition receptors. Following its expression, IFN-alpha
      embarks upon a complex downstream signalling cascade called the JAK/STAT pathway.
      This signalling pathway results in the expression of hundreds of effector genes
      known as interferon stimulated genes (ISGs). These genes are the basis for an
      elaborate effector mechanism and ultimately, the clearance of viral infection.
      ISGs mark an elegant mechanism of anti-viral host defence that warrants renewed
      research focus in our global efforts to treat existing and emerging viruses. By
      understanding the mechanistic role of individual ISGs we anticipate the discovery
      of a new "treasure trove" of anti-viral mediators that may pave the way for more
      effective, targeted and less toxic anti-viral therapies. Therefore, with the aim
      of highlighting the value of the innate type 1 IFN response in our battle against
      viral infection, this review outlines both historic and recent advances in
      understanding the IFN-alpha JAK/STAT pathway, with a focus on new research
      discoveries relating to specific ISGs and their potential role in curing existing
      and future emergent viral infections.

PMID- 28432381
TI  - Modulation of the multidrug efflux pump EmrD-3 from Vibrio cholerae by Allium
      sativum extract and the bioactive agent allyl sulfide plus synergistic
      enhancement of antimicrobial susceptibility by A. sativum extract.
AB  - The causative agent of cholera, Vibrio cholerae, is a public health concern.
      Multidrug-resistant V. cholerae variants may reduce chemotherapeutic efficacies
      of severe cholera. We previously reported that the multidrug efflux pump EmrD-3
      from V. cholerae confers resistance to multiple structurally distinct
      antimicrobials. Medicinal plant compounds are potential candidates for EmrD-3
      efflux pump modulation. The antibacterial activities of garlic Allium sativum,
      although poorly understood, predicts that a main bioactive component, allyl
      sulfide, modulates EmrD-3 efflux. Thus, we tested whether A. sativum extract acts
      in synergy with antimicrobials and that a main bioactive component allyl sulfide
      inhibits EmrD-3 efflux. We found that A. sativum extract and allyl sulfide
      inhibited ethidium bromide efflux in cells harboring EmrD-3 and that A. sativum
      lowered the MICs of multiple antibacterials. We conclude that A. sativum and
      allyl sulfide inhibit EmrD-3 and that A. sativum extract synergistically enhances
      antibacterial agents.

PMID- 28432382
TI  - Two distinct periplasmic enzymes are responsible for tellurite/tellurate and
      selenite reduction by strain ER-Te-48 associated with the deep sea hydrothermal
      vent tube worms at the Juan de Fuca Ridge black smokers.
AB  - Strain ER-Te-48 isolated from a deep-ocean hydrothermal vent tube worm is capable
      of resisting and reducing extremely high levels of tellurite, tellurate, and
      selenite, which are used for respiration anaerobically. Tellurite and tellurate
      reduction is accomplished by a periplasmic enzyme of 215 kDa comprised of 3
      subunits (74, 42, and 25 kDa) in a 2:1:1 ratio. The optimum pH and temperature
      for activity is 8.0 and 35  degrees C, respectively. Tellurite reduction has a V
      max of 5.6 umol/min/mg protein and a K m of 3.9 mM. In the case of the tellurate
      reaction, V max and K m were 2.6 umol/min/mg protein and 2.6 mM, respectively.
      Selenite reduction is carried out by another periplasmic enzyme with a V max of
      2.8 umol/min/mg protein, K m of 12.1 mM, and maximal activity at pH 6.0 and 38 
      degrees C. This protein is 165 kDa and comprised of 3 subunits of 98, 44, and 23
      kDa in a 1:1:1 ratio.

PMID- 28432383
TI  - Increased blood cadmium levels were not associated with increased fracture risk
      but with increased total mortality in women: the Malmo Diet and Cancer Study.
AB  - : This study aimed to investigate if high levels of blood cadmium at baseline
      were associated with increased fracture risk during follow-up in middle-aged
      women. No increased fracture risk was observed during follow-up, but women with
      higher levels of cadmium had an increased overall mortality. INTRODUCTION:
      Exposure to high levels of cadmium has been associated with an increased fracture
      risk. The aim was to investigate a perceived association between low levels of
      blood cadmium (B-Cd) at baseline and risk of first incident fracture. METHODS:
      From the population-based Malmo Diet and Cancer Study Cardiovascular cohort, 2920
      middle-aged women with available background questionnaire and B-Cd measurements
      were included. Women were divided into quartiles (Q) according to their cadmium
      levels (Cd-Q1 <0.18 MUg/L, Cd-Q2 0.18-0.28 MUg/L, Cd-Q3 0.28-0.51 MUg/L, and Cd
      Q4 >0.51 MUg/L). National registries were analysed for prospective risk of
      fractures or death. Associations between B-Cd and fracture risk were assessed by
      survival analysis (Cox regression analysis). RESULTS: In total, 998 first
      incident fractures occurred in women during a follow-up lasting 20.2 years
      (median) (12.5-21.2 years) (25th-75th percentile). Women in Cd-Q4 were more often
      current smokers than in Cd-Q1 78.4 vs. 3.3% (p < 0.001) and the number of
      cigarettes smoked per day correlated with B-Cd (r = 0.49; p < 0.001). The risk of
      fracture was not associated with baseline B-Cd in adjusted models. The hazard
      ratio (HR) Cd-Q4 vs. Cd-Q1 was 1.06 (95% confidence interval (CI) 0.89-1.27). In
      the multivariate Cox regression, independent variables for increased fracture
      risk were history of gastric ulcer and increasing age, whereas increasing body
      mass index (BMI) lowered fracture risk. Overall mortality was significantly
      higher for women with high B-Cd, HR 2.06 (95% CI 1.57-2.69). CONCLUSIONS: Higher
      blood levels of cadmium did not increase fracture risk in middle-aged women but
      reduced overall survival.

PMID- 28432384
TI  - The probability of object-scene co-occurrence influences object identification
      processes.
AB  - Contextual information allows the human brain to make predictions about the
      identity of objects that might be seen and irregularities between an object and
      its background slow down perception and identification processes. Bar and
      colleagues modeled the mechanisms underlying this beneficial effect suggesting
      that the brain stocks information about the statistical regularities of object
      and scene co-occurrence. Their model suggests that these recurring regularities
      could be conceptualized along a continuum in which the probability of seeing an
      object within a given scene can be high (probable condition), moderate
      (improbable condition) or null (impossible condition). In the present experiment,
      we propose to disentangle the electrophysiological correlates of these context
      effects by directly comparing object-scene pairs found along this continuum. We
      recorded the event-related potentials of 30 healthy participants (18-34 years
      old) and analyzed their brain activity in three time windows associated with
      context effects. We observed anterior negativities between 250 and 500 ms after
      object onset for the improbable and impossible conditions (improbable more
      negative than impossible) compared to the probable condition as well as a parieto
      occipital positivity (improbable more positive than impossible). The brain may
      use different processing pathways to identify objects depending on whether the
      probability of co-occurrence with the scene is moderate (rely more on top-down
      effects) or null (rely more on bottom-up influences). The posterior positivity
      could index error monitoring aimed to ensure that no false information is
      integrated into mental representations of the world.

PMID- 28432385
TI  - Bioresorbable vascular scaffolds in coronary chronic total occlusions
      revascularization: safety assessment related to struts coverage and apposition in
      6-month OCT follow-up.
AB  - Beneficial properties of bioresorbable vascular scaffolds (BVS) regarding to
      vasomotility restoration and no caging of the vessel make them attractive devices
      in chronic total occlusions (CTO) revascularization. However, more evidence is
      needed attending to their use in this specific setting. We aim to determine
      feasibility and safety of BVS use in CTO revascularization attending to struts
      coverage and apposition, as well as re-stenosis and stent thrombosis (ST) rates.
      29 BVS were deployed in 9 CTO lesions revascularization (mean J-CTO score >=3)
      with an acute procedural success rate of 100%. Clinical and angiographic follow
      up was performed 6 months later, including intracoronary analyses from optical
      coherence tomography (OCT) images. 44,723 struts were analyzed within the total
      636 mm of scaffolded vessel. Mean length scaffolded per lesion was 70.66 +/-
      31.01 mm with a mean number of 3.22 BVS. 2051 struts (4.59%) were identified as
      uncovered, being most of them (98.4%) neither malapposed nor disrupted. Mean
      thickness of struts' coverage was 0.13 +/- 0.05 mm. Incomplete strut apposition
      (ISA) percentage was 0% as no malapposed struts were detected and 134 struts were
      identified as disrupted, which represents a 0.29% from the total. Mean vessel,
      scaffold, and lumen diameters were 3.87 +/- 0.51, 2.97 +/- 0.49, and 2.68 +/-
      0.50 mm, respectively. Neither in-stent re-stenosis nor ST was detected. During
      follow-up, none of our patients died, suffered from stroke or needed target
      lesion revascularization. Clinical and angiographic 6-month follow-up (including
      OCT analyses) of BVS in CTO revascularization suggests their effectiveness and
      safety, even in very complex chronic occluded lesions. Nevertheless, more
      evidence is needed.

PMID- 28432386
TI  - Is a Routine Chest X-ray Necessary in Every Patient After Percutaneous CT-Guided
      Lung Biopsy? A Retrospective Review of 278 Cases.
AB  - PURPOSE: To determine the rate, clinical significance, and predictors of delayed
      pneumothorax after CT-guided lung biopsy. METHODS: Medical and imaging records of
      all patients who underwent CT-guided lung biopsy between January 1, 2012, and
      January 9, 2015, were reviewed. "Early pneumothorax" was defined as one
      visualized on CT scan at the time of biopsy, "delayed pneumothorax" as one
      discovered on the first follow-up chest X-ray (CXR), and "clinically significant
      pneumothorax" as one requiring chest tube placement. RESULTS: Three hundred fifty
      seven lung biopsies were performed; 79 patients did not have follow-up CXR and
      were excluded. Out of 278 cases included in the study, early pneumothorax
      occurred in 109 patients. Follow-up CXRs were available in the remaining 169
      patients without early pneumothorax and were obtained 3.1 +/- 2.9 h after biopsy.
      The rate of delayed pneumothorax was 8.6% (24/278). Clinically significant
      pneumothorax occurred in 10/24 (41.7%) patients with delayed pneumothorax,
      including one case of tension pneumothorax. Patients with delayed pneumothorax (n
      = 24) had smaller lesion long axial diameter (18.58 +/- 9.84 vs 25.83 +/- 17.69
      mm, p = 0.005), longer intrapulmonary needle tract (23.45 +/- 14.98 vs 14.17 +/-
      14.49, p = 0.004), and lower FEV1/FVC ratio (53.30 +/- 22.47 vs 71.15 +/- 13.77,
      p = 0.015), compared to those without delayed pneumothorax (n = 145). The length
      of intrapulmonary needle tract was the only independent predictor of delayed
      pneumothorax (p = 0.008) and symptomatic delayed pneumothorax (p = 0.019).
      CONCLUSION: Obtaining a routine follow-up CXR in all patients after CT-guided
      lung biopsy appears warranted, given the high rate of delayed pneumothorax and
      large percentage of patients who will require a chest tube. The only independent
      predictor of (symptomatic) delayed pneumothorax was the length of intrapulmonary
      needle tract.

PMID- 28432387
TI  - Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular
      Cholangiocarcinoma.
AB  - PURPOSE: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare mixed
      cell type primary liver cancer with limited data to guide management.
      Transarterial radioembolization with yttrium-90 microspheres (RE) is an emerging
      treatment option for both hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma. This study explored the safety and efficacy of RE for
      unresectable cHCC-CC. METHODS: Patients with histopathologically confirmed cHCC
      CC treated with RE were retrospectively evaluated. Clinical and biochemical
      toxicities were assessed using the Common Toxicity Criteria for Adverse Events
      v4.03. Radiological response was analyzed using the Response Criteria in Solid
      Tumors (RECIST) v1.1 and modified RECIST criteria. Survival times were calculated
      and prognostic variables identified. RESULTS: Ten patients (median age 59 years;
      six men, four women) with unresectable cHCC-CC underwent 14 RE treatments with
      resin (n = 6 patients) or glass (n = 4 patients) microspheres. Clinical
      toxicities were limited to grade 1-2 fatigue, anorexia, nausea, or abdominal
      pain. No significant biochemical toxicities were observed. Median overall
      survivals from the first RE treatment and from initial diagnosis were 10.2 and
      17.7 months, respectively. Six of seven patients with elevated tumor biomarker
      levels before RE showed decreased levels after treatment (median decrease of 72%,
      range 13-80%). Best hepatic radiological response was 60% partial response and
      40% stable disease by modified RECIST, and 100% stable disease by RECIST v1.1.
      Poor performance status and the presence of macrovascular invasion were
      identified as predictors of reduced survival after RE. CONCLUSION: RE appears to
      be a safe and promising treatment option for patients with unresectable cHCC-CC.
      LEVEL OF EVIDENCE: Level 4.

PMID- 28432389
TI  - [University Pathology in Germany].

PMID- 28432390
TI  - Biomass Resources: Agriculture.
AB  - Bioenergy is the single largest source of renewable energy in the European Union
      (EU-28); of this, 14% was produced from agricultural feedstocks in 2012. This
      chapter provides an overview of the current use (for bioenergy) and future
      potential of agricultural feedstocks for (amongst others) biorefinery purposes in
      the European Union. The main application of these feedstocks is currently the
      production of biofuels for road transport. Biodiesel makes up 80% of the European
      biofuel production, mainly from rapeseed oil, and the remaining part is
      bioethanol from wheat and sugar beet. Dedicated woody and grassy crops (mainly
      miscanthus and switchgrass) are currently only used in very small quantities for
      heat and electricity generation. There is great potential for primary
      agricultural residues (mainly straw) but currently only part of this is for heat
      and electricity generation. Agricultural land currently in use for energy crop
      cultivation in the EU-28 is 4.4 Mio ha, although the land area technically
      available in 2030 is estimated to be 16-43 Mio ha, or 15-40% of the current
      arable land in the EU-28. There is, however, great uncertainty on the location
      and quality of that land. It is expected that woody and grassy crops together
      with primary agricultural residues should become more important as agricultural
      feedstocks.

PMID- 28432391
TI  - Patterns and Outcomes of Recurrent Esophageal Cancer After Curative
      Esophagectomy.
AB  - BACKGROUND: The recurrence patterns and therapeutic outcomes of patients with
      recurrent esophageal cancer after curative esophagectomy are not fully
      understood. METHODS: Data on recurrence patterns and sites of recurrence in
      patients with recurrent esophageal cancer after curative esophagectomy from 2005
      to 2015 were retrospectively analyzed. Time to recurrence after curative
      esophagectomy and survival after recurrence were compared among groups stratified
      by recurrence pattern and site. Multivariate analysis was performed to identify
      clinicopathological parameters influencing survival after recurrence. RESULTS: Of
      the 290 patients identified, a single pattern of recurrence occurred in 224
      patients (77.2%) and a multiple pattern of recurrence occurred in 66 patients
      (22.8%). The most frequent recurrence pattern was lymph node in 173 patients
      (59.7%), followed by distant organ in 133 patients (45.9%). Median time to
      recurrence and median survival after recurrence of all patients were 228 and 327
      days, respectively. Among patients with lymph node or lung recurrence, there were
      5-year survivors after recurrence who underwent multimodal therapy. Multivariate
      analysis revealed that longer disease-free interval [hazard ratio (HR) 0.70, 95%
      confidence interval (95% CI) 0.52-0.93], single pattern of recurrence (HR 0.54,
      95% CI 0.39-0.74), and curative treatment for recurrence (HR 0.17, 95% CI 0.10
      0.28) were significantly associated with favorable prognosis. CONCLUSIONS:
      Although the prognosis of recurrent esophageal cancer remains unfavorable, if
      multimodal treatment that includes local therapy was curative, prognosis could
      improve, especially in patients with lymph node or lung recurrence.

PMID- 28432392
TI  - Rare Appearance, Rare Location and Unusual Patient Age : Report of Osteolytic
      Fibrous Dysplasia in the Temporal Bone of a 52-year-old Patient.

PMID- 28432394
TI  - [Vitamin D and UV protection].
AB  - A high percentage of people present with reduced vitamin D3 levels. Reduced
      vitamin D3 levels have to be supplemented. Oral supplementation can be performed
      easily and without significant side effects. Because vitamin D3 can be produced
      in the skin via ultraviolet B (UVB) irradiation, it is possible to elevate
      reduced vitamin D3 levels by UVB exposure. However, UVB, which is classified as a
      complete carcinogen, induces skin cancer. Therefore, UVB irradiation should not
      be utilized to stimulate vitamin D3 synthesis. Sun protection, especially wearing
      of clothes and seeking shade and appropriate use of sunscreens, correlates with
      reduced D3 levels. A risk-benefit calculation shows that oral supplementation of
      vitamin D3 is preferred to UVB/sun expsure to increase serum vitamin D3 levels.

PMID- 28432393
TI  - More functions of torpor and their roles in a changing world.
AB  - Increased winter survival by reducing energy expenditure in adult animals is
      often viewed as the primary function of torpor. However, torpor has many other
      functions that ultimately increase the survival of heterothermic mammals and
      birds. In this review, we summarize new findings revealing that animals use
      torpor to cope with the conditions during and after natural disasters, including
      fires, storms, and heat waves. Furthermore, we suggest that torpor, which also
      prolongs longevity and was likely crucial for survival of mammals during the time
      of the dinosaur extinctions, will be advantageous in a changing world. Climate
      change is assumed to lead to an increase in the occurrence and intensity of
      climatic disasters, such as those listed above and also abnormal floods,
      droughts, and extreme temperatures. The opportunistic use of torpor, found in
      many heterothermic species, will likely enhance survival of these challenges,
      because these species can reduce energy and foraging requirements. However, many
      strictly seasonal hibernators will likely face the negative consequences of the
      predicted increase in temperature, such as range contraction. Overall, available
      data suggest that opportunistic heterotherms with their flexible energy
      requirements have an adaptive advantage over homeotherms in response to
      unpredictable conditions.

PMID- 28432395
TI  - The magnetic resonance imaging appearance of the anterolateral ligament of the
      knee in association with anterior cruciate rupture.
AB  - OBJECTIVE: The magnetic resonance imaging (MRI) appearance of the anterolateral
      ligament (ALL) has been described. However, the appearance of this structure and
      injury, in the presence of anterior cruciate ligament (ACL) injury, is less well
      defined. We studied the incidence of injury to the ALL and the pattern of this
      injury on MRI. MATERIALS AND METHODS: Following Institutional Review Board
      approval, a retrospective study of 375 consecutive MRI studies was performed.
      Cases were identified from a prospective database of ACL reconstruction patients.
      Following exclusions, 280 MRIs (277 patients; 197 males: 80 females; mean age
      30.2 years, range, 16-54) were evaluated. Injury was defined as full thickness,
      partial thickness, or an avulsion fracture. Each study was independently assessed
      by two consultant musculoskeletal radiologists. RESULTS: Injury to the ALL was
      identified (by at least one observer) in only 10.7% of cases (2.50% full
      thickness, 7.50% partial thickness, and 0.71% avulsion fracture). There was an
      almost perfect level of interobserver agreement for both the identification of an
      injury (kappa = 0.854) and grading of injury (kappa = 0.858). The MRI incidence
      of ALL injury was significantly greater within 6 weeks of the knee injury (18.5
      vs. 8.37%; p < 0.05). CONCLUSIONS: ALL injury was identified in only one-tenth of
      cases of ACL rupture. MRI changes can be reliably identified with strong
      agreement between observers. ALL injury is found more frequently on MRI within 6
      weeks of the knee injury (compared to scans performed after this time period)
      suggesting that some injuries may resolve or become less visible.

PMID- 28432396
TI  - Weight-bearing computed tomography findings in varus ankle osteoarthritis:
      abnormal internal rotation of the talus in the axial plane.
AB  - OBJECTIVES: To assess the incidence of abnormal internal rotation of the talus in
      the axial plane in patients with varus ankle osteoarthritis, and to determine
      whether this incidence differs from the severity of varus ankle osteoarthritis
      (moderate versus severe). MATERIALS AND METHODS: We retrospectively evaluated
      weight-bearing computed tomography (CT) and plain radiographs of 52 ankles with
      no abnormalities (control group) and 96 ankles with varus osteoarthritis (varus
      OA group), which were further stratified into a moderate-OA subgroup (50 ankles)
      and a severe-OA subgroup (46 ankles). A new radiographic parameter on weight
      bearing CT, the talus rotation ratio, was used to assess the rotation of the
      talus in the axial plane. The normal range of the talus rotation ratio was
      defined as the 95% prediction interval for talus rotation ratio values in the
      control group. Abnormal internal rotation of the talus was defined for talus
      rotation ratio values above the normal range. We determined the incidence of
      abnormal internal rotation of the talus in the varus-OA group, moderate-OA
      subgroup, and severe-OA subgroup. RESULTS: In the varus-OA group, the incidence
      of abnormal internal rotation of the talus was 45% (43 ankles), which
      corresponded to an incidence of 32% (16 ankles) in the moderate-OA subgroup and
      59% (27 ankles) in the severe-OA subgroup (p = 0.013). CONCLUSION: Our study
      demonstrates that abnormal internal rotation of the talus occurs in patients with
      varus ankle osteoarthritis, and is more frequently noted in severe than in
      moderate varus ankle osteoarthritis.

PMID- 28432397
TI  - Downregulation of neuropilin-1 on macrophages modulates antibody-mediated
      tumoricidal activity.
AB  - Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune
      functions via various mechanisms. In this study, we investigated the role of NRP
      1 on macrophages in antibody-mediated tumoricidal activity. Treatment of
      macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody
      significantly suppressed antibody-dependent cellular cytotoxicity and modulated
      cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using
      a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)
      positive breast cancer xenografts showed that antibody-mediated antitumor
      activity and tumor infiltration of CD4+ T lymphocytes were significantly
      downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked
      down were co-administered with an anti-HER2 antibody. These results revealed that
      NRP-1 expressed on macrophages plays an important role in antibody-mediated
      antitumor immunity. Taken together, the induction of NRP-1 on macrophages may be
      a therapeutic indicator for antibody treatments that exert antibody-dependent
      cellular cytotoxicity activity, although further studies are needed in order to
      support this hypothesis.

PMID- 28432398
TI  - ECTES-Abstracts 2017.

PMID- 28432399
TI  - [When is surgical resection of metastases in testicular germ cell tumors
      indicated and is there a scientific basis?]
AB  - Surgical resection of metastases represents an integral part of curative
      management in patients with testicular germ cell tumors (GCT). Primary nerve
      sparing retroperitoneal lymph node dissection (nsRPLND) for low volume metastases
      in clinical stages I-IIB has to be differentiated from the more complex and more
      extensive postchemotherapeutic procedures. In Europe, primary nerve-sparing
      retroperitoneal lymph node dissection (nsRPLND) for clinical stage I
      nonseminomatous GCT (NSGCT) plays a subordinate. In clinical stage IIA/B, nsRPLND
      is indicated for patients with marker-negative metastases in whom cure rates of
      about 65% can be achieved with surgery alone. For clinical stage IIA/B seminomas,
      nsRPLND represents an individual, still experimental procedure with high cure
      rates. Postchemotherapy residual tumor resection (pRTR) for advanced seminomas is
      only indicated in the context of a FDG-PET/CT-positive residual mass >3 cm in
      diameter. For NSGCT, pRTR is indicated in patients with residual masses >1 cm and
      negative or plateauing tumor markers to resect persisting teratoma or vital
      cancer. Complete resection of all masses including resection of adjacent
      vascular, visceral or skeletal metastases is mandatory to achieving the highest
      cure rate possible. Due to the complexity and the lower rate of significant
      morbidity and mortality, these procedures should be done at tertiary referral
      centers.

PMID- 28432400
TI  - [The intestinal microbiome and metabolic diseases : From obesity to diabetes and
      nonalcoholic steatohepatitis].
AB  - BACKGROUND: The intestinal microbiome consists of about 10 million genes, many of
      which encode digestive enzymes. This explains why animal and human experiments
      revealed that the intestinal microbiome adapts to food intake and optimizes
      energy harvest from food. This function is considered beneficial in states of
      lack of food, but following overnutrition, it might support the development of
      obesity. OBJECTIVES: The relevance of the intestinal microbiome for the
      pathogenesis of obesity and associated metabolic diseases such as fatty liver
      disease and type 2 diabetes mellitus and for the clinical management of such
      diseases shall be discussed. MATERIALS AND METHODS: Recent literature related to
      the topic has been selected, presented, and discussed with regard to the
      objectives. RESULTS: The intestinal microbiome plays a role in the pathogenesis
      of both obesity (by increasing the energy absorption from food) and fatty liver
      disease as well as type 2 diabetes mellitus (via induction of low-grade
      inflammation following translocation of lipopolysaccharides from the gut and
      dysregulation of metabolic pathways). CONCLUSIONS: The findings might have
      consequences for diagnosis (identification of risk groups) and therapy (usage of
      known and novel probiotics or bacterial metabolites) of metabolic diseases.

PMID- 28432401
TI  - Erratum to: Capacity of muscle derived stem cells and pericytes to promote tendon
      graft integration and ligamentization following anterior cruciate ligament
      reconstruction.

PMID- 28432402
TI  - Predictors of missed appointments in patients referred for congenital or
      pediatric cardiac magnetic resonance.
AB  - BACKGROUND: Congenital cardiac magnetic resonance is a limited resource because
      of scanner and physician availability. Missed appointments decrease scheduling
      efficiency, have financial implications and represent missed care opportunities.
      OBJECTIVE: To characterize the rate of missed appointments and identify
      modifiable predictors. MATERIALS AND METHODS: This single-center retrospective
      study included all patients with outpatient congenital or pediatric cardiac MR
      appointments from Jan. 1, 2014, through Dec. 31, 2015. We identified missed
      appointments (no-shows or same-day cancellations) from the electronic medical
      record. We obtained demographic and clinical factors from the medical record and
      assessed socioeconomic factors by U.S. Census block data by patient ZIP code.
      Statistically significant variables (P<0.05) were included into a multivariable
      analysis. RESULTS: Of 795 outpatients (median age 18.5 years, interquartile range
      13.4-27.1 years) referred for congenital cardiac MR, a total of 91 patients
      (11.4%) missed appointments; 28 (3.5%) missed multiple appointments. Reason for
      missed appointment could be identified in only 38 patients (42%), but of these,
      28 (74%) were preventable or could have been identified prior to the appointment.
      In multivariable analysis, independent predictors of missed appointments were
      referral by a non-cardiologist (adjusted odds ratio [AOR] 5.8, P=0.0002),
      referral for research (AOR 3.6, P=0.01), having public insurance (AOR 2.1,
      P=0.004), and having scheduled cardiac MR from November to April (AOR 1.8,
      P=0.01). CONCLUSION: Demographic factors can identify patients at higher risk for
      missing appointments. These data may inform initiatives to limit missed
      appointments, such as targeted education of referring providers and patients.
      Further data are needed to evaluate the efficacy of potential interventions.

PMID- 28432403
TI  - Bone marrow fat content in 70 adolescent girls with anorexia nervosa: Magnetic
      resonance imaging and magnetic resonance spectroscopy assessment.
AB  - BACKGROUND: Adolescents and women with anorexia nervosa have increased bone
      marrow fat and decreased bone formation, at least in part due to hormonal changes
      leading to preferential stem cell differentiation to adipocytes over osteoblasts.
      OBJECTIVE: The purpose of this study was to evaluate marrow fat content and
      correlate with age and disease severity using knee MRI with T1 relaxometry (T1-R)
      and MR spectroscopy (MRS) in 70 adolescents with anorexia nervosa. MATERIALS AND
      METHODS: We enrolled 70 girls with anorexia nervosa who underwent 3-T knee MRI
      with coronal T1-W images, T1-R and single-voxel proton MRS at 30 and 60 ms TE.
      Metaphyses were scored visually on the T1-W images for red marrow. Visual T1
      score, T1 relaxometry values, MRS lipid indices and fat fractions were analyzed
      by regression on age, body mass index (BMI) and bone mineral density (BMD) as
      disease severity markers. MRS measures included unsaturated fat index, T2 water,
      unsaturated and saturated fat fractions. RESULTS: All red marrow measures
      declined significantly with age. T1-R values were associated negatively with BMI
      and BMD for girls <=16 years (P=0.03 and P=0.002, respectively) and positively
      for those>=17 years (P=0.05 and P=0.003, respectively). MRS identified a strong
      inverse association between T2 water and saturated fat fraction from 60 ms TE
      data (r=-0.85, P<0.0001). There was no association between unsaturated fat index
      and BMI or BMD. CONCLUSIONS: The association between T1 and BMI and BMD among
      older girls suggests more marrow fat in those with severe anorexia nervosa. In
      contrast, the physiological association between marrow fat content and age
      remained dominant in younger patients. The strong association between T2 water
      and saturated fat may relate to the restricted mobility of water with increasing
      marrow fat.

PMID- 28432404
TI  - Pediatric neuro MRI: tricks to minimize sedation.
AB  - Magnetic resonance imaging (MRI) is the workhorse modality in pediatric
      neuroimaging because it provides excellent soft-tissue contrast without ionizing
      radiation. Until recently, studies were uninterpretable without sedation;
      however, given development of shorter sequences, sequences that correct for
      motion, and studies showing the potentially deleterious effects of sedation on
      immature laboratory animals, it is prudent to minimize sedation when possible.
      This manuscript provides basic guidelines for performing pediatric neuro MRI
      without sedation by both modifying technical factors to reduce scan time and
      noise, and using a multi-disciplinary team to coordinate imaging with the
      patient's biorhythms.

PMID- 28432405
TI  - [Extracorporeal membrane oxygenation : System selection, (contra)indications, and
      management].
AB  - There are a large number of extracorporeal membrane oxygenation (ECMO) systems
      and configurations. Thorough planning and evaluation of specific therapeutic
      needs are necessary to tailor ECMO therapy to the individual patient situation.
      Indications tend towards lowering the threshold towards respiratory ECMO.
      Patients with severe acute respiratory distress syndrome (ARDS) not improving to
      optimization of ventilation and supportive therapeutic measures potentially
      qualify for ECMO. Contraindications are relative and have to be considered in the
      light of the individual risk-benefit ratio. The same is true for decisions to
      stop ECMO therapy in case of futility for which reliable evidence does not exist.

PMID- 28432407
TI  - The arterial supply of the nipple areola complex (NAC) and its relations: an
      analysis of angiographic CT imaging for breast pedicle design.
AB  - PURPOSE: To investigate the blood supply to the nipple areola complex (NAC) on
      thoracic CT angiograms (CTA) to improve breast pedicle design in reduction
      mammoplasty. METHODS: In a single centre, CT scans of the thorax were
      retrospectively reviewed for suitability by a cardiothoracic radiologist.
      Suitable scans had one or both breasts visible in extended fields, with contrast
      enhancement of breast vasculature in a female patient. The arterial sources,
      intercostal space perforated, glandular/subcutaneous course, vessel entry point,
      and the presence of periareolar anastomoses were recorded for the NAC of each
      breast. RESULTS: From 69 patients, 132 breasts were suitable for inclusion. The
      most reproducible arterial contribution to the NAC was perforating branches
      arising from the internal thoracic artery (ITA) (n = 108, 81.8%), followed by the
      long thoracic artery (LTA) (n = 31, 23.5%) and anterior intercostal arteries (AI)
      (n = 21, 15.9%). Blood supply was superficial versus deep in (n = 86, 79.6%) of
      ITA sources, (n = 28, 90.3%) of LTA sources, and 10 (47.6%) of AI sources. The
      most vascularly reliable breast pedicle would be asymmetrical in 7.9% as a
      conservative estimate. CONCLUSION: We suggest that breast CT angiography can
      provide valuable information about NAC blood supply to aid customised pedicle
      design, especially in high-risk, large-volume breast reductions where the risk of
      vascular-dependent complications is the greatest and asymmetrical dominant
      vasculature may be present. Superficial ITA perforator supplies are predominant
      in a majority of women, followed by LTA- and AIA-based sources, respectively.

PMID- 28432408
TI  - A rare anastomosis between the common hepatic artery and the superior mesenteric
      artery: a case report.
AB  - For decades, anastomoses between unpaired branches of the abdominal aorta have
      attracted the attention of anatomists, surgeons and radiologists, due to their
      significance in many clinical procedures. This report presents a rare anastomosis
      between the common hepatic artery and the superior mesenteric artery, which gave
      off three branches to the jejunum. The diameter of the anastomosis measured at
      the point of its branching off the common hepatic artery and at the level of
      union with the superior mesenteric artery was 4.46 and 4.19 mm, respectively.
      Moreover, the anastomosis gave off the branch to the head of the pancreas. Both
      embryological background and potential clinical implications of this variation
      are discussed. Knowledge of these vascular connections may be important for
      diagnostic and surgical procedures.

PMID- 28432410
TI  - Complete radiologic and molecular response of HIV-negative primary effusion
      lymphoma with short-course lenalidomide.

PMID- 28432409
TI  - Innovative treatment modalities for urinary incontinence: a European survey
      identifying experience and attitude of healthcare providers.
AB  - INTRODUCTION AND HYPOTHESIS: Urinary incontinence is a common condition in women,
      with a reported prevalence ranging from 25% to 51%. Of these women, an estimated
      38% suffer from stress urinary incontinence (SUI). A European research consortium
      is investigating an innovative system based on information and communication
      technology for the conservative treatment of women with SUI. When introducing a
      new intervention, implementation barriers arise and need to be identified.
      Therefore, we investigated healthcare providers' experience with and attitude
      towards innovative care options. METHODS: We performed an online survey to assess
      (1) the characteristics and practice of healthcare providers, (2) current
      protocols for SUI, (3) current use of biofeedback, and (4) knowledge about
      serious gaming. The survey was sent to members of professional societies in
      Europe (EUGA), UK (BSUG) and The Netherlands (DPFS). RESULTS: Of 341
      questionnaires analyzed (response rate between 18% and 30%), 64% of the
      respondents had access to a protocol for the treatment of SUI, and 31% used
      biofeedback when treating patients with SUI. However, 92% considered that
      biofeedback has a clear or probable added value, and 97% of those who did not use
      biofeedback would change their practice if research evidence supported its use.
      Finally, 89% of respondents indicated that they had no experience of serious
      gaming, but 92% considered that it could be useful. CONCLUSIONS: Although
      inexperienced, European urogynecologists and physical therapists welcome
      innovative treatment options for the conservative treatment of SUI such as
      portable wireless biofeedback and serious gaming. Scientific evidence is
      considered a prerequisite to incorporate such innovations into clinical practice.

PMID- 28432411
TI  - Donor lymphocyte infusion reversed graft rejection in matched-unrelated donor
      hematopoietic stem cell transplantation for a child with thalassemia.

PMID- 28432412
TI  - Genotyping-by-sequencing targeting of a novel downy mildew resistance gene Pl 20
      from wild Helianthus argophyllus for sunflower (Helianthus annuus L.).
AB  - KEY MESSAGE: Genotyping-by-sequencing revealed a new downy mildew resistance
      gene, Pl 20 , from wild Helianthus argophyllus located on linkage group 8 of the
      sunflower genome and closely linked to SNP markers that facilitate the marker
      assisted selection of resistance genes. Downy mildew (DM), caused by Plasmopara
      halstedii, is one of the most devastating and yield-limiting diseases of
      sunflower. Downy mildew resistance identified in wild Helianthus argophyllus
      accession PI 494578 was determined to be effective against the predominant and
      virulent races of P. halstedii occurring in the United States. The evaluation of
      114 BC1F2:3 families derived from the cross between HA 89 and PI 494578 against
      P. halstedii race 734 revealed that single dominant gene controls downy mildew
      resistance in the population. Genotyping-by-sequencing analysis conducted in the
      BC1F2 population indicated that the DM resistance gene derived from wild H.
      argophyllus PI 494578 is located on the upper end of the linkage group (LG) 8 of
      the sunflower genome, as was determined single nucleotide polymorphism (SNP)
      markers associated with DM resistance. Analysis of 11 additional SNP markers
      previously mapped to this region revealed that the resistance gene, named Pl 20 ,
      co-segregated with four markers, SFW02745, SFW09076, S8_11272025, and
      S8_11272046, and is flanked by SFW04358 and S8_100385559 at an interval of 1.8
      cM. The newly discovered P. halstedii resistance gene has been introgressed from
      wild species into cultivated sunflower to provide a novel gene with DM
      resistance. The homozygous resistant individuals were selected from BC2F2
      progenies with the use of markers linked to the Pl 20 gene, and these lines
      should benefit the sunflower community for Helianthus improvement.

PMID- 28432415
TI  - Use of Computer Imaging in Rhinoplasty: A Survey of the Practices of Facial
      Plastic Surgeons.
AB  - OBJECTIVE: The objective of this study was to quantify the use of computer
      imaging by facial plastic surgeons. METHODS: AAFPRS Facial plastic surgeons were
      surveyed about their use of computer imaging during rhinoplasty consultations.
      The survey collected information about surgeon demographics, practice settings,
      practice patterns, and rates of computer imaging (CI) for primary and revision
      rhinoplasty. For those surgeons who used CI, additional information was also
      collected, which included who performed the imaging and whether the patient was
      given the morphed images after the consultation. RESULTS: A total of 238 out of
      1200 (19.8%) facial plastic surgeons responded to the survey. Out of those who
      responded, 195 surgeons (83%) were board certified by the American Board of
      Facial Plastic and Reconstructive Surgeons (ABFPRS). The majority of respondents
      (150 surgeons, 63%) used CI during rhinoplasty consultation. Of the surgeons who
      use CI, 92% performed the image morphing themselves. Approximately two-thirds of
      surgeons who use CI gave their patient a printout of the morphed images after the
      consultation. CONCLUSIONS: Computer imaging (CI) is a frequently utilized tool
      for facial plastic surgeons during cosmetic consultations with patients. Based on
      these results of this study, it can be suggested that the majority of facial
      plastic surgeons who use CI do so for both primary and revision rhinoplasty. As
      more sophisticated systems become available, it is possible that utilization of
      CI modalities will increase. This provides the surgeon with further tools to use
      at his or her disposal during discussion of aesthetic surgery. LEVEL OF EVIDENCE
      V: This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 28432416
TI  - Commentary on 3D Photogrammetric Analysis of the Nasal Tip Projection and
      Derotation Based on the Nasal Tip Quadripod Concept.
AB  - Asian noses are mainly characterized by a low nasal dorsum, a short nose and an
      underprojected nasal tip due to underdeveloped (short and weak) alar cartilages.
      The goals of the surgery are to increase the tip projection, elongate the nose
      and augment the dorsum. In Asian noses the structural approach helps strengthen
      the weak cartilages and add definition to the nasal tip. There are various
      methods to increase tip projection and definition. Columellar strut, caudal
      septal extension graft, tip grafts and lateral crural grafts in order to elongate
      the upper legs of the nasal tip tripod can be used. The method described in this
      article seems a useful solution in Asian rhinoplasty patients who do not want to
      use rib cartilage. The "Skiff Graft" functions similar to caudal septal extension
      graft with its elongation and raise effect at the caudal septum. However in cases
      which need significant increase in tip projection and nose elongation, this
      method may be insufficient. In such cases, stronger structural grafts prepared
      from rib cartilage will give a better tip definition and more predictable
      outcome.

PMID- 28432417
TI  - Exploring the Possibility of a Retrograde Embolism Pathway from the Facial Artery
      to the Ophthalmic Artery System In Vivo.
AB  - BACKGROUND: Blindness caused by soft tissue fillers is an extremely low
      probability event, but it results in great concern because of its devastating
      consequences. Currently, the mechanism of an embolism is usually considered to be
      an accidental injection of fillers into the blood vessels of the face, such as a
      facial artery, and then retrograding into the ophthalmic artery system, which
      causes retinal ischemic necrosis. In addition, previous studies have shown that
      there are anastomoses between facial arteries and branches of the ophthalmic
      artery in cadavers. An in vivo study, however, has not yet been reported.
      METHODS: This study was approved by the institutional review board of Xijing
      Hospital, Fourth Military Medical University. Under general anesthesia, we
      dissected the same side of the face and eyeball in rabbits to manifest the facial
      artery and retina separately. Later, a needle (27 g) connected to a syringe (10
      ml) full of methylene blue was inserted into a rabbit facial artery. Then, after
      poking a tiny hole in the central retinal artery, methylene blue was injected
      into the facial artery as quickly as possible (0.5 ml per second). At the same
      time, we carefully observed whether the central retinal artery had dye spillover
      or staining in the sclera. If blue dye was observed in the eye ground and/or the
      sclera, then it was thought to have entered the ophthalmic artery system (a
      positive result). In contrast, if none of the blue dye was observed, it was
      considered a negative result. A Chi-square (chi 2) test with a fourfold table was
      used to compare the differences in the frequencies of blue dye observed between
      living and dead rabbits. A value of p < 0.05 was considered significant. RESULTS:
      One of the 20 rabbits showed the appearance of blue dye in the ophthalmic artery
      system in vivo, and the remaining 19 living rabbits had negative results. All 20
      of the dead rabbits showed dye appearance in the eye ground. A statistically
      significant difference existed between the living and dead rabbits (p < 0.05).
      CONCLUSION: In vivo, fillers can retrogradely enter the ophthalmic artery if the
      fillers entered the facial artery. Although the possibility is much lower in vivo
      than it is in corpses, adequate attention should be paid because of the
      catastrophic complications. LEVEL OF EVIDENCE V: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266 .

PMID- 28432418
TI  - ["Because we feel, we have to do something" - Barriers in the prevention of
      violence and key areas requiring action : A qualitative interview study with
      professional nurses and managers in the field of elderly care].
AB  - BACKGROUND: In recent years, politics and society have shown an increasing
      interest in the prevention of violence. Despite the scientific studies and
      prevention programs that have been conducted over the past few years, there is no
      indication that the prevalence of violence in elderly care is falling. A high
      number of unreported cases may still be assumed. OBJECTIVE: The present study
      examined the barriers in transferring research knowledge into practice.
      Furthermore, it dealt with the requirements of an interventional approach which
      is practical and which effectively addresses the barriers. MATERIAL AND METHODS:
      The data were collected in qualitative interviews (n = 20) and analyzed by using
      qualitative content analysis. RESULTS: The study revealed uncertainties in
      dealing with violence. The institutions lacked a clear definition of violence and
      the respondents did not have a clear concept of when and where violence starts. A
      high proportion of the respondents stated that violence occurred in various forms
      in daily nursing care but that there were no specific strategies for action. Only
      very few cases were documented at all. Moreover, a lack of practical further
      training was reported. The visibility of these barriers opens up new approaches
      to developing preventive measures which work in practice. CONCLUSION: A common
      definition of violence, clear and binding standards, regular training and
      education measures are central to the prevention of violence in care.

PMID- 28432419
TI  - [Driving and dementia : An issue for general practice?!]
AB  - BACKGROUND: With most forms of dementia, the risk of road traffic accidents
      increases with disease progression. Addressing the issue of fitness to drive at
      an early stage can help to reduce driving-related risks and simultaneously
      preserve mobility. General practitioners (GPs) are central contact persons for
      dementia patients and their relatives in medical and psychosocial matters, and
      also play a key role in addressing the issue of driving safety. OBJECTIVE:
      Identification of relevant aspects of managing fitness to drive in dementia, as
      well as of support requirements for German general practice. MATERIALS AND
      METHODS: Seven focus groups with dementia patients, family caregivers and GPs
      were conducted in order to define the different requirements for counselling in
      the general practice setting. The transcribed discussions were analysed by a
      multiprofessional research team using content analysis. RESULTS: For people with
      dementia, declining mobility and driving cessation is related to a loss of
      autonomy. Addressing fitness to drive in dementia is thus a subject of conflict
      and uncertainty for both family caregivers and GPs. The difficulties include the
      assessment of fitness to drive in the general practice setting, concerns about
      compromising the patient-physician relationship by raising the issue of driving
      fitness, as well as uncertainties about the GP's own role. GPs consider the
      involvement of caregivers to be important to successfully address the topic of
      driving safety and organise alternative transport. Support is required in the
      form of criteria defining the time point at which fitness to drive should be
      assessed, information on compensation possibilities and mobility alternatives.
      CONCLUSION: Resource-oriented and patient-centred development of management
      strategies for limited mobility is needed in general practice. Finding the
      correct balance between documentation, adequately informing the patient and
      establishing patient-centred strategies represents a challenge.

PMID- 28432420
TI  - Sex differences in neuromuscular function after repeated eccentric contractions
      of the knee extensor muscles.
AB  - PURPOSE: This study examined the mechanisms for force and power reduction during
      and up to 48 h after maximal eccentric contractions of the knee extensor muscles
      in young men and women. METHODS: 13 men (22.8 +/- 2.6 years) and 13 women (21.6
      +/- 2.2 years) performed 150 maximal effort eccentric contractions (5 sets of 30)
      with the knee extensor muscles at 60 degrees  s-1. Maximal voluntary isometric
      contractions (MVIC) and maximal voluntary concentric contractions (MVCC) were
      performed before and after the 150 eccentric contractions. The MVCCs involved a
      set of two isokinetic contractions at 60 degrees  s-1 and sets of isotonic
      contractions performed at seven different resistance loads (1 N m, 10, 20, 30,
      40, 50, and 60% MVIC). Electrical stimulation was used during the MVICs and at
      rest to determine changes in voluntary activation and contractile properties.
      RESULTS: At baseline, men were stronger than women (MVIC: 276 +/- 48 vs. 133 +/-
      37 N m) and more powerful (MVCC: 649 +/- 77 vs. 346 +/- 78 W). At termination of
      the eccentric contractions, voluntary activation, resting twitch amplitude, and
      peak power during concentric contractions at the seven loads and at 60 degrees  s
      1 decreased (P < 0.05) similarly in the men and women. At 48 h post-exercise, the
      MVIC torque, power (for loads >=20-60% MVIC), and voluntary activation remained
      depressed (P < 0.05), but the resting twitch had returned to baseline (P > 0.05)
      with no sex differences. CONCLUSION: Central mechanisms were primarily
      responsible for the depressed maximal force production up to 48 h after repeated
      eccentric contractions of the knee extensors and these mechanisms were similar in
      men and women.

PMID- 28432421
TI  - The effect of nitric oxide synthase inhibition with and without inhibition of
      prostaglandins on blood flow in different human skeletal muscles.
AB  - PURPOSE: Animal studies suggest that the inhibition of nitric oxide synthase
      (NOS) affects blood flow differently in different skeletal muscles according to
      their muscle fibre type composition (oxidative vs glycolytic). Quadriceps femoris
      (QF) muscle consists of four different muscle parts: vastus intermedius (VI),
      rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) of which VI
      is located deep within the muscle group and is generally regarded to consist
      mostly of oxidative muscle fibres. METHODS: We studied the effect of NOS
      inhibition on blood flow in these four different muscles by positron emission
      tomography in eight young healthy men at rest and during one-leg dynamic
      exercise, with and without combined blockade with prostaglandins. RESULTS: At
      rest blood flow in the VI (2.6 +/- 1.1 ml/100 g/min) was significantly higher
      than in VL (1.9 +/- 0.6 ml/100 g/min, p = 0.015) and RF (1.7 +/- 0.6 ml/100
      g/min, p = 0.0015), but comparable to VM (2.4 +/- 1.1 ml/100 g/min). NOS
      inhibition alone or with prostaglandins reduced blood flow by almost 50% (p <
      0.001), but decrements were similar in all four muscles (drug * muscle
      interaction, p = 0.43). During exercise blood flow was also the highest in VI
      (45.4 +/- 5.5 ml/100 g/min) and higher compared to VL (35.0 +/- 5.5 ml/100
      g/min), RF (38.4 +/- 7.4 ml/100 g/min), and VM (36.2 +/- 6.8 ml/100 g/min). NOS
      inhibition alone did not reduce exercise hyperemia (p = 0.51), but combined NOS
      and prostaglandin inhibition reduced blood flow during exercise (p = 0.002),
      similarly in all muscles (drug * muscle interaction, p = 0.99). CONCLUSION: NOS
      inhibition, with or without prostaglandins inhibition, affects blood flow
      similarly in different human QF muscles both at rest and during low-to-moderate
      intensity exercise.

PMID- 28432423
TI  - Note on the coefficient of variations of neuronal spike trains.
AB  - It is known that many neurons in the brain show spike trains with a coefficient
      of variation (CV) of the interspike times of approximately 1, thus resembling the
      properties of Poisson spike trains. Computational studies have been able to
      reproduce this phenomenon. However, the underlying models were too complex to be
      examined analytically. In this paper, we offer a simple model that shows the same
      effect but is accessible to an analytic treatment. The model is a random walk
      model with a reflecting barrier; we give explicit formulas for the CV in the
      regime of excess inhibition. We also analyze the effect of probabilistic synapses
      in our model and show that it resembles previous findings that were obtained by
      simulation.

PMID- 28432422
TI  - Country differences of psychosocial working conditions in Europe: the role of
      health and safety management practices.
AB  - BACKGROUND: In times of demographic change, maintaining health and employability
      of older employees is important. In this context, studies show that stressful
      working conditions differ by countries. Yet, it is unclear if specific national
      management practices to deal with these conditions contribute towards explaining
      country differences. METHODS: This study combines two different data sources. The
      first one provides detailed information on psychosocial working conditions in 17
      European countries, based on 12,284 employees from the Survey of Health, Ageing
      and Retirement in Europe (SHARE) and the English Longitudinal Study of Ageing
      (ELSA). We link this information to the second data source that provides
      information on health and safety management practices in each of the countries
      under study (collected among 17,477 managers at the level of companies in the
      Enterprise survey on new and emerging risks (ESENER)). We distinguish six
      different types of risk management procedures in the analysis. RESULTS: Results
      show that levels of psychosocial risks are generally lower in countries with more
      developed management practices, in particular if national management practices
      are marked by (1) procedures to deal with work stress, (2) information about whom
      to address in case of work-related psychosocial problems, and (3) health and
      safety services provided by psychologists. CONCLUSION: The findings underline the
      importance of a comprehensive psychosocial risk management approach in reducing
      work-related stress, as lower levels of psychosocial risks are linked to specific
      psychosocial risk management practices within companies, in particular those
      pointing to clear responsibilities and coordinated procedures in dealing with
      psychosocial risks.

PMID- 28432424
TI  - Variations of isovaline structure related to activity in the formalin foot assay
      in mice.
AB  - Current centrally acting analgesics such as opioids are associated with adverse
      effects that limit their use and threaten patient safety. Isovaline is a novel
      prototype analgesic that produces peripheral antinociception in several pain
      models with little or no effect on the central nervous system. The aim of this
      study was to establish a preliminary structure-activity relationship for
      isovaline derivatives by assaying efficacy in the formalin foot assay and central
      adverse effect profile in mice. Selected compounds were tested using the formalin
      foot assay to determine efficacy in reducing formalin-induced behaviors. Of the
      compounds tested, R-isovaline, S-isovaline, and 1-amino-1-cyclobutanecarboxylic
      acid reduced nocifensive behavior in phase II of the assay. These effects
      occurred without affecting performance on the rotarod, indicating that the
      reduction in nocifensive behaviors was not due to sedation or motor
      incoordination. Modifications to isovaline that increased its steric size without
      a cyclobutane ring formation produced compounds with no activity in the formalin
      foot assay. These findings indicate that the conformational stability of
      isovaline or the ability to form a cyclobutane ring is necessary for activity in
      the formalin foot assay.

PMID- 28432425
TI  - The problem with myelomeningoceles, hydrocephalus, and progressive neurological
      deficits-what do we know?

PMID- 28432426
TI  - Posterior cranial fossa tumours in children at National Cancer Institute, Sudan:
      a single institution experience.
AB  - BACKGROUND: Posterior cranial fossa tumours (PCF) comprise 54-70% of childhood
      brain tumours. The clinical profile and outcomes of these tumours differ in area
      of the world. The aim of this study is to describe clinical characteristics,
      treatment and outcome of posterior cranial fossa tumours in Sudan. MATERIAL AND
      METHODS: A retrospective study of children diagnosed with posterior cranial fossa
      tumours and treated between January 1998 and December 2015 at National Cancer
      Institute, Sudan. RESULTS: A total of 31 paediatric patients with a posterior
      cranial fossa brain tumour were identified over the study period. The mean age
      was 7.9 years (standard deviation (SD) = 3.37). Females were slightly more
      affected (51%) than males (49%), and the majority of patients were from rural
      areas (71%). Brainstem tumours were the most frequent tumour type (48%) followed
      by medulloblastoma (36%). The mean pre-diagnostic symptomatic interval was 3.6
      months (SD = 3.95). Overall survival rate of our total study population at 1, 2
      and 5 years was 23, 19 and 13%, respectively. CONCLUSION: Overall, this study
      draws attention to the situation of paediatric brain tumours in Sudan. Late
      presentation, misdiagnosis and limited diagnostic and treatment resources are
      challenges that may contribute to poor outcome in these patients.

PMID- 28432427
TI  - Concurrent paediatric medulloblastoma and Chiari I malformation with
      syringomyelia.

PMID- 28432429
TI  - Enhanced production of recombinant proteins by a small molecule protein synthesis
      enhancer in combination with an antioxidant in recombinant Chinese hamster ovary
      cells.
AB  - The improvement in the production of recombinant proteins has been linked in a
      number of small molecules such as carboxylic acids to the inhibition of histone
      deacetylase, leading to increased transcription of genes. However, carboxylic
      acids such as pentanoic acid and butanoic acid have been shown to promote an
      apoptotic response in Chinese hamster ovary (CHO) cell culture. Supplementation
      of cultures with antioxidants has shown the ability to reduce the apoptotic
      response of carboxylic acid supplementation, leading to increased therapeutic
      protein production. In this study, we showed that pentanoic acid reduced the
      number of cells entering early apoptosis relative to butanoic acid by 15.4%.
      Additionally, supplementation of butanoic acid- and pentanoic acid-treated
      cultures with N-acetyl cysteine (NAC) reduced the population of cells entering
      early apoptosis by 5.3 and 10.0%, respectively, while increasing productivity by
      19.5% in the presence of pentanoic acid and NAC. Conversely, a decrease of 5.7%
      in production was observed in response to combined butanoic acid and N-acetyl
      cysteine treatment. The results presented herein provide evidence that a culture
      supplementation method is critical for optimization of biopharmaceutical
      manufacturing processes.

PMID- 28432430
TI  - Changes in quick phases of downbeat nystagmus during visual fixation.

PMID- 28432428
TI  - Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis.
AB  - Uncontrolled massive bleeding with subsequent derangement of the coagulation
      system is a major challenge in the management of both surgical and seriously
      injured patients. Under physiological conditions activators and inhibitors of
      coagulation regulate the sensitive balance between clot formation and
      fibrinolysis. In some cases, excessive and diffuse bleeding is caused by systemic
      activation of fibrinolysis, i. e. hyperfibrinolysis (HF). Uncontrolled HF is
      associated with a high mortality. Polytrauma patients and those undergoing
      surgical procedures involving organs rich in plasminogen proactivators (e. g.
      liver, kidney, pancreas, uterus and prostate gland) are at a high risk for HF.
      Antifibrinolytics, such as tranexamic acid (TXA) are used for prophylaxis and
      treatment of bleeding caused by a local or generalized HF as well as other
      hemorrhagic conditions. TXA is a synthetic lysine analogue that has been
      available in Austria since 1966. TXA is of utmost importance in the prevention
      and treatment of traumatic and perioperative bleeding due to the resulting
      reduction in perioperative blood loss and blood transfusion requirements. The
      following article presents the different fields of application of TXA with
      particular respect to indications and dosages, based on a literature search and
      on current guidelines.

PMID- 28432431
TI  - Initial cell adhesion of three cell types in the presence and absence of serum
      proteins.
AB  - With the development of a wide range of new biomaterials for the sensing of
      different cell behaviour, it is important to consider whether the cells tested in
      vitro are in direct contact with the material or whether cell-biomaterial contact
      is mediated by an interfacial layer of proteins originating from the culture
      medium or from the cells themselves. Thus, this study describes the differences
      between the cell adhesion mediated by proteins originating from foetal bovine
      serum and without the presence of such proteins 2 h following cell seeding
      exemplarily with different cell types (an osteoblastic cell line, primary
      fibroblasts, and mesenchymal stem cells). Three of the examined cell types were
      found to react differently to differing conditions in terms of cell shape, area,
      and number. Nevertheless, the expression and localization of the various proteins
      involved in cell adhesion and signalling (CD44, vinculin, talin, actin, focal
      adhesion kinase, Rho-GTPases and extracellular signal-regulated kinases 1 and 2)
      were, in general, similar with respect to all the cell types tested, albeit
      varying according to the presence or absence of serum. Moreover, no classical
      focal adhesions were formed during cell adhesion without serum proteins, while
      different signalling pathways were involved in this process. The study
      systematically describes and discusses the cell adhesion of three different human
      cell types to a well-known substrate without the presence of external proteins
      and it is hoped that this knowledge will be subsequently applied in biomaterial
      applications in which the presence of external proteins is undesirable (e.g. for
      biosensing purposes).

PMID- 28432432
TI  - TGFbeta splicing and canonical pathway activation in high-grade serous carcinoma.
AB  - The present study analyzed the expression and clinical role of the transforming
      growth factor-beta (TGFbeta) pathway in high-grade serous carcinoma (HGSC), with
      focus on malignant effusions. TGFbeta1-3 and TGFbetaRI-III mRNA expression by qRT
      PCR was analyzed in 70 HGSC effusions and 55 solid specimens (28 ovarian, 27
      abdominal metastases). Protein expression of Smad2 and Smad3 and their
      phosphorylated forms by Western blotting was analyzed in 73 specimens (42
      effusions, 13 ovarian carcinomas, 18 solid metastases). Expression was analyzed
      for association with anatomic site and clinical parameters, including survival.
      TGFbetaRI and TGFbetaRII mRNA was overexpressed in effusions and solid
      metastases, particularly the former, compared to that in the ovarian tumors (p <
      0.001 to p = 0.05), with anatomic site-dependent expression of splice variants.
      Conversely, Smad2, p-Smad2, and p-Smad3 were overexpressed in solid specimens
      (ovarian and peritoneal) compared to those in effusions (p < 0.001 for all). In
      univariate survival analysis, higher TGFbetaRI variant 1 and TGFbetaRIII mRNA
      levels were associated with a trend for shorter overall survival in patients with
      post-chemotherapy effusions (p = 0.066 and p = 0.087, respectively), and the
      latter was an independent prognostic marker in Cox multivariate analysis (p =
      0.041). Smad3 protein expression was associated with a trend for shorter overall
      survival in univariate survival analysis (p = 0.052). TGFbeta receptor splice
      variant expression is anatomic site-dependent in HGSC. Elevated levels of TGFbeta
      signaling pathway mRNAs are seen in metastatic HGSC, but are not accompanied by
      increased Smad expression and activation in HGSC effusions, evidence of failure
      to activate canonical TGFbeta signaling. Assessment of the prognostic role of
      this pathway in HGSC effusions merits further research.

PMID- 28432433
TI  - Glypican-3 mRNA expression level in Wilms tumor: correlation with histological
      type, stage, and outcome.
AB  - PURPOSE: To correlate expression of Glypican-3 in Wilms tumor with
      histopathology, stage, and outcome. METHODS: Glypican-3 mRNA expression by real
      time PCR on tumor and normal germline samples from 75 fresh nephrectomies for
      Wilms tumor with fold change after normalization against GAPDH was compared.
      Survival analysis for event-free and overall survival (EFS, OS) with 2-year
      follow-up for Glypican-3 overexpression (>1.5 times) and clinicopathological
      parameters was performed. RESULTS: Glypican-3 was overexpressed in 37/75 (49.3%).
      It was overexpressed in 77% (10/13) cases with blastema predominance or
      anaplastic histology, as compared to 44% of other histologies (27/62) (p = 0.03).
      OS was 73 and 93%, respectively (p = 0.016), for those with and without GPC-3
      overexpression. EFS was not significantly different with Glypican-3
      overexpression (p = 0.11). All 5 deaths among blastema predominant tumors and 4/5
      deaths among triphasic tumors had overexpressed Glypican-3. Most deaths in Stage
      IV, Stage III, and Stage I + II (5/7, 3/3, 1/1) had GPC-3 overexpression. On
      multivariate analysis, only histology and stage were found to have independent
      prognostic value. CONCLUSION: Glypican-3 overexpression in Wilms tumor correlates
      with poor OS on univariate analysis. However, only histology and stage have
      independent prognostic value. Glypican-3 levels may help to stratify intermediate
      outcome histology (triphasic) and Stage III Wilms tumors.

PMID- 28432434
TI  - Ventricular androgenic-anabolic steroid-related remodeling: an
      immunohistochemical study.
AB  - BACKGROUND: Several fatal cases of bodybuilders, following a myocardial
      infarction after long exposure to androgenic-anabolic steroids (AAS), are
      reported. In recent years, evidence has emerged of cases of heart failure related
      to AAS consumption, with no signs of coronary or aorta atherosclerosis. This
      study aims to further investigate the pathogenesis of the ventricular AAS-related
      remodeling performing immunohistochemistry (IHC). METHOD: In order to examine
      innate immunity activity and myocytes and endothelial cell apoptosis, IHC
      analyses were performed on heart tissue of two cases of bodybuilders who died
      after years of supratherapeutic use of metelonone and nandrolone and where no
      atherosclerosis or thrombosis were found, using the following antibodies: anti
      CD68, anti-iNOS, anti-CD163, anti-CD 15, anti-CD8, anti-CD4, anti-HIF1 alpha, and
      in situ TUNEL staining. RESULTS: Results confirm the experimental findings of
      recent research that, in the absence of other pathological factors, if intensive
      training is combined with AAS abuse, myocytes and endothelial cells undergo
      apoptotic alterations. The absence of inflammatory reactions and the presence of
      an increased number of M2 macrophages in the areas of fibrotic remodeling confirm
      that the fibrotic changes in the heart are apoptosis-related and not necrosis
      related. CONCLUSIONS: In conclusion, the study indicates that, in very young
      subjects with chronic hypoxia-related alterations of the heart, signs of a heart
      failure in the other organs and a history of AAS abuse, death can be ascribed to
      progressive heart failure due to the direct apoptotic cardiac and endothelial
      changes produced by AAS.

PMID- 28432435
TI  - C4/5 foraminal stenosis predicts C5 palsy after expansive open-door laminoplasty.
AB  - INTRODUCTION: Laminoplasty is frequently performed in cervical myelopathy
      patients, but can lead to unexpected postoperative C5 palsy. Although several
      studies have examined the pathogenesis and prevention of postoperative C5 palsy,
      many controversies remain and some radiological findings identified as risk
      factors were not correlated with our outcomes. PURPOSE: This study sought
      reliable radiological findings that predict C5 palsy after laminoplasty and
      examined why the predictors of C5 palsy did not apply in our series. METHODS:
      This study reviewed 116 patients who underwent open-door laminoplasty for
      cervical spondylotic myelopathy between January 2014 and April 2016,
      retrospectively. C5 palsy was defined as weakness of the deltoid muscle. We
      evaluated the incidence of C5 palsy, the preoperative C2-7 Cobb's angle, and
      Pavlov ratio at the C4/C5 level using simple cervical lateral radiographs. We
      also evaluated the existence of an ossified posterior longitudinal ligament, the
      transverse diameter of the C4/5 foramen, and increases in the anteroposterior
      diameter of the spinal canal at the C4/5 levels after surgery. Furthermore, a
      high signal intensity on T2-weighted images of the cervical spinal cord
      preoperatively was noted. RESULTS: Of the 116 patients, 16 cases were excluded
      and 100 cases were analyzed; postoperative C5 palsy occurred in 8 patients (8%).
      There were no significant differences between the two groups except the average
      diameter of the C4/5 foramen. A diameter of the C4/5 foramen of less than 2 mm
      was significantly related to C5 palsy in the binary logistic regression test.
      CONCLUSIONS: A smaller diameter of the C4/5 foramen was the only factor
      significantly correlated with C5 palsy after laminoplasty. The results suggest
      that C4/5 foraminal stenosis is one of the best predictors of C5 palsy, which
      might be related to ischemic/reperfusion injury of the C5 root nerve after
      laminoplasty.

PMID- 28432438
TI  - Abstracts of the MASCC/ISOO 2017 Annual Meeting.

PMID- 28432436
TI  - Chemokine Involvement in Lung Injury Secondary to Ischaemia/Reperfusion.
AB  - INTRODUCTION: During transplant surgeries, the lung experiences an ischaemia
      reperfusion (I/R)-induced damage identified as a significant cause of morbidity
      and mortality. However, the mechanisms by which I/R induces leucocyte
      accumulation and subsequent tissue damage in lung surgeries remain unknown.
      Therefore, the present study aims to assess the role of monocyte chemotactic
      protein 1 (MCP-1) and macrophage inflammatory protein 2 (MIP-2) in leucocyte
      chemotaxis related to lung injury secondary to I/R. METHODS: Six pigs were
      subjected to an orthotopic left caudal lobe lung transplantation with a
      subsequent 60-min graft reperfusion (Transplant group). In addition, six animals
      underwent to sham surgery (Sham Group). Plasma samples and lung biopsies were
      collected before the beginning of pneumonectomy, before starting the reperfusion,
      and 30 min and 60 min after the beginning of the reperfusion. Plasma levels of
      intercellular adhesion molecule 1 (ICAM-1) and lung expressions of MCP-1, MIP-2,
      myeloperoxidase (MPO), and lung oedema were measured. RESULTS: Lung I/R caused
      substantial damage observed as pulmonary oedema. The oedema was evident after the
      ischemic insult and increased after reperfusion. After reperfusion, increased
      levels of MPO were observed which suggests an activation and infiltration of
      neutrophils into the lung tissue. After 30 min of reperfusion, MCP-1, MIP-2, and
      ICAM-1 levels were significantly increased compared to prepneumonectomy levels (p
      < 0.05) and a further increase was observed after 60 min of reperfusion (p <
      0.05). CONCLUSION: The present study demonstrates that activated neutrophils, as
      well as MCP-1, MIP-2, and ICAM-1, are involved in inflammatory response induced
      by ischaemia-reperfusion-induced lung injury.

PMID- 28432437
TI  - An Italian multicentre study on adult atopic dermatitis: persistent versus adult
      onset disease.
AB  - Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease which
      predominantly affects children. However, AD may persist until adulthood
      (persistent AD), or directly start in adults (adult-onset AD). AD often shows a
      non-flexural rash distribution, and atypical morphologic variants in adults and
      specific diagnostic criteria are lacking. Moreover, adult AD prevalence as well
      as detailed data which can characterize persistent vs adult-onset subtype are
      scant. The aim of this study was to investigate on the main features of adult AD
      particularly highlighting differences between persistent vs adult-onset form. An
      Italian multicentre observational study was conducted between April 2015-July
      2016 through a study-specific digital database. 253 adult AD patients were
      enrolled. Familiar history of AD was negative in 81.0%. Erythemato-desquamative
      pattern was the most frequent clinical presentation (74.3%). Flexural surface of
      upper limbs was most commonly involved (47.8%), followed by eyelid/periocular
      area (37.9%), hands (37.2%), and neck (32%). Hypertension (7.1%) and thyroiditis
      (4.3%) were the most frequent comorbidities. A subgroup analysis between
      persistent (59.7%) vs adult-onset AD patients (40.3%) showed significant results
      only regarding AD severity (severe disease was more common in persistent group, p
      < 0.05), itch intensity (higher in adult-onset disease), and comorbidities
      (hypertension was more frequent in adult-onset group, p < 0.01). Adult AD showed
      uncommon features such as significant association with negative AD family history
      and lacking of association with systemic comorbidities respect to general
      population. No significant differences among persistent vs adult-onset subgroup
      were registered except for hypertension, itch intensity, and disease severity.

PMID- 28432439
TI  - Characterization of a functional recombinant human creatine kinase-MB isoenzyme
      prepared by tandem affinity purification from Escherichia coli.
AB  - Creatine kinase isoform CK-MB has been widely applied as a biomarker of
      myocardial injury. While a variety of methods have been used to measure CK-MB
      activity or mass in clinical laboratories, a CK-MB standard is needed to
      eliminate between-method bias. Because the in vitro expression of human creatine
      kinase generates three isoenzymes, CK-MM, CK-MB, and CK-BB, it is important to
      establish an effective method to purify the isoform CK-MB from the mixture. In
      this study, we aimed at using tandem affinity purification (TAP) to purify
      recombinant CK-MB protein and evaluate its value in clinical laboratories. After
      the optimized sequence coding CK-M and CK-B were synthesized, they were combined
      with TAP tags (6His and SBP) and inserted into a pRSFDuet vector; then, the
      constructed 6His-CK-M-SBP-CK-B-pRSF plasmid was transformed into Escherichia coli
      BL21 (DE3) for expression. After TAP, we obtained purified CK-MB protein. We also
      did recovery testing using the engineered CK-MB and standard CK-MB (Randox) at
      different concentrations, and the results suggested that the engineered CK-MB
      could be used as the reference material. Moreover, the stability study of
      recombinant CK-MB showed high stability during long-term storage at -80  degrees
      C. In conclusion, the TAP-purified recombinant CK-MB protein may be a much better
      and cheaper standard or reference material for clinical laboratories.

PMID- 28432440
TI  - Application of recombinant Pediococcus acidilactici BD16 (fcs +/ech +) for
      bioconversion of agrowaste to vanillin.
AB  - Biotechnological production of vanillin is gaining momentum as the natural
      synthesis of vanillin that is very expensive. Ferulic acid (FA), a costly
      compound, is used as the substrate to produce vanillin biotechnologically and the
      making process is still expensive. Therefore, this study investigated the
      practical use of an agrobiomass waste, rice bran, and provides the first evidence
      of a cost-effective production of vanillin within 24 h of incubation using
      recombinant Pediococcus acidilactici BD16 (fcs +/ech +). Introduction of two
      genes encoding feruloyl CoA synthetase and enoyl CoA hydratase into the native
      strain increased vanillin yield to 4.01 g L-1. Bioconversion was monitored
      through the transformation of phenolic compounds. A hypothetical metabolic
      pathway of rice bran during the vanillin bioconversion was proposed with the
      inserted pathway from ferulic acid to vanillin and compared with that of other
      metabolic engineered strains. These results could be a gateway of using
      recombinant lactic acid bacteria for industrial production of vanillin from
      agricultural waste.

PMID- 28432441
TI  - Direct quantification of lipopeptide biosurfactants in biological samples via
      HPLC and UPLC-MS requires sample modification with an organic solvent.
AB  - The rapid and accurate quantification of biosurfactants in biological samples is
      challenging. In contrast to the orcinol method for rhamnolipids, no simple
      biochemical method is available for the rapid quantification of lipopeptides.
      Various liquid chromatography (LC) methods are promising tools for relatively
      fast and exact quantification of lipopeptides. Here, we report strategies for the
      quantification of the lipopeptides pseudofactin and surfactin in bacterial
      cultures using different high- (HPLC) and ultra-performance liquid chromatography
      (UPLC) systems. We tested three strategies for sample pretreatment prior to LC
      analysis. In direct analysis (DA), bacterial cultures were injected directly and
      analyzed via LC. As a modification, we diluted the samples with methanol and
      detected an increase in lipopeptide recovery in the presence of methanol.
      Therefore, we suggest this simple modification as a tool for increasing the
      accuracy of LC methods. We also tested freeze-drying followed by solvent
      extraction (FDSE) as an alternative for the analysis of "heavy" samples. In FDSE,
      the bacterial cultures were freeze-dried, and the resulting powder was extracted
      with different solvents. Then, the organic extracts were analyzed via LC. Here,
      we determined the influence of the extracting solvent on lipopeptide recovery.
      HPLC methods allowed us to quantify pseudofactin and surfactin with run times of
      15 and 20 min per sample, respectively, whereas UPLC quantification was as fast
      as 4 and 5.5 min per sample, respectively. Our methods provide highly accurate
      measurements and high recovery levels for lipopeptides. At the same time, UPLC-MS
      provides the possibility to identify lipopeptides and their structural isoforms.

PMID- 28432443
TI  - Progastrin: a potential predictive marker of liver metastasis in colorectal
      cancer.
AB  - BACKGROUND AND AIMS: Staging of colorectal cancer often fails to discriminate
      outcomes of patients with morphologically similar tumours that exhibit different
      clinical behaviours. Data from several studies suggest that the gastrin family of
      growth factors potentiates colorectal cancer tumourigenesis. The aim of this
      study was to investigate whether progastrin expression may predict clinical
      outcome in colorectal cancer. METHODS: Patients with colorectal adenocarcinoma of
      identical depth of invasion who had not received neoadjuvant therapy were
      included. The patients either had stage IIa disease with greater than 3-year
      disease-free survival without adjuvant therapy or stage IV disease with liver
      metastases on staging CT. Progastrin expression in tumour sections was scored
      with reference to the intensity and area of immunohistochemical staining.
      RESULTS: Progastrin expression by stage IV tumours was significantly greater than
      stage IIa tumours with mean progastrin immunopositivity scores of 2.1 +/- 0.2
      versus 0.5 +/- 0.2, respectively (P < 0.001). CONCLUSIONS: This is the first
      study to show that progastrin expression may be predictive of aggressive tumour
      behaviour in patients with colorectal cancer and supports its clinical relevance
      and potential use as a biomarker.

PMID- 28432442
TI  - Smokeless tobacco products harbor diverse bacterial microbiota that differ across
      products and brands.
AB  - Smokeless tobacco products contain numerous chemical compounds, including known
      human carcinogens. Other smokeless tobacco constituents, including bacteria, may
      also contribute to adverse health effects among smokeless tobacco users. However,
      there is a lack of data regarding the microbial constituents of smokeless
      tobacco. Our goal was to characterize the bacterial microbiota of different
      smokeless tobacco products and evaluate differences across product types and
      brands. DNA was extracted from 15 brands of smokeless tobacco products (including
      dry snuff, moist snuff, snus, and Swedish snus) and 6 handmade products (e.g.,
      toombak) using an enzymatic and mechanical lysis approach. Bacterial community
      profiling was performed using PCR amplification of the V1-V2 hypervariable region
      of the 16S rRNA gene, followed by 454 pyrosequencing of the resulting amplicons
      and sequence analysis using the QIIME package. Total viable counts were also
      determined to estimate the number of viable bacteria present in each product.
      Average total viable counts ranged from 0 to 9.35 * 107 CFU g-1. Analysis of the
      16S rRNA gene sequences revealed high bacterial diversity across the majority of
      products tested: dry snuff products where characterized by the highest diversity
      indices compared to other products. The most dominant bacterial phyla across all
      products were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes.
      Significant differences in both bacterial community composition and in silico
      predicted gene content were observed between smokeless tobacco product types and
      between brands of specific smokeless tobacco products. These data are useful in
      order to comprehensively address potential health risks associated with the use
      of smokeless tobacco products.

PMID- 28432444
TI  - Endoscopic ultrasonography and computed tomography scanning for preoperative
      staging of colonic cancer.
AB  - PURPOSE: With an increasing demand for more accurate preoperative staging methods
      for colon cancer, we aimed to compare preoperative tumour (T)- and nodal (N)
      stage in patients with left-sided colon cancer by endoscopic ultrasonography
      (EUS) and computed tomography (CT) with post-operative histology as gold
      standard. METHODS: A total of 44 patients were prospectively recruited at Herlev
      and Roskilde University Hospitals during November 2014-January 2016. Thirty-five
      patients were included in the final analysis and underwent EUS, CT and surgery
      within 2 weeks. Diagnostic values were evaluated for "low risk" (T1+T2+T3 with
      <=5 mm extramural invasion) and "high risk" (T3 with >5 mm of extramural spread +
      T4) colonic cancer. RESULTS: Sensitivity and specificity in "low risk" colonic
      cancer evaluated with EUS was 0.90 [0.74;0.98] and 0.75 [0.19;0.99] and with CT
      0.96 [0.80;0.99] and 0.25 [<0.01;0.81]. EUS and CT were poor in predicting N0 or
      N+ disease. CONCLUSIONS: The sensitivity of EUS and CT were good and comparable
      regarding T-stage evaluation, while EUS had a significantly higher specificity in
      the evaluation of "low risk" tumours. The results obtained for "high risk"
      colonic cancer were difficult to evaluate due to small patient numbers. EUS could
      be considered as a supplement to CT scans in selecting patients for neoadjuvant
      therapies, or local transmural treatment, in the future. TRIAL REGISTRATION:
      NCT02324023.

PMID- 28432445
TI  - The impact of transportation and translocation on dispersal behaviour in the
      invasive cane toad.
AB  - Biological invasions transport organisms to novel environments; but how does the
      translocation process influence movement patterns of the invader? Plausibly, the
      stress of encountering a novel environment, or of the transport process, might
      induce rapid dispersal from the release site-potentially enhancing (or reducing)
      invader success and spread. We investigated the effect of transportation and
      release to novel environments on dispersal-relevant traits of one of the world's
      most notorious invaders, the cane toad (Rhinella marina). We collected toads in
      northern New South Wales from heath and woodland habitats, manipulated the level
      of transport stress and either returned toads to their exact collection point
      (residents) or reciprocally translocated them to a novel site. Both translocation
      and the level of transport stress drastically altered toad dispersal rates for at
      least 5 days post-release. Translocated toads (depending on their level of
      transport stress and release habitat) moved on average two to five times further
      per day (mean range 67-148 m) than did residents (mean range 22-34 m).
      Translocated toads also moved on more days, and moved further from their release
      point than did resident toads, but did not move in straighter lines. A higher
      level of transport stress (simulating long-distance translocation) had no
      significant effect on movements of resident toads but amplified the dispersal of
      translocated toads only when released into woodland habitat. These behavioural
      shifts induced by translocation and transportation may affect an invader's
      ability to colonise novel sites, and need to be incorporated into plans for
      invader control.

PMID- 28432447
TI  - Twofold minimum variance beamforming for enhanced ultrasound imaging.
AB  - PURPOSE: To calculate the optimal weights of a minimum variance (MV) beamformer,
      the covariance matrix of the received data should be estimated. In ultrasound
      imaging, it is done through spatial smoothing. However, this technique reduces
      the effective aperture and consequently limits the attainable resolution. To
      mitigate this effect, we propose a new configuration for applying an adaptive
      beamforming method. METHODS: The method is based on applying MV in a twofold
      configuration such that the outputs of the subarrays are combined through an
      adaptive MV-like beamformer, instead of simply summing them. In this way, a fully
      adaptive beamformer is obtained. RESULTS: Applying the method on a phantom
      containing point targets has shown that off-axis signals are attenuated more in
      comparison to MV. This results in a lowered mainlobe width and decreased sidelobe
      levels. Moreover, simulation results of a cyst phantom confirm the superiority of
      the method over the MV in terms of contrast. CONCLUSION: The method yields
      significant improvement in the resolving capability and the contrast compared
      with the conventional MV. At the presence of the steering vector errors, these
      superiorities were achieved at a cost of slightly more errors in estimating the
      reflectivity coefficients.

PMID- 28432446
TI  - Biasing spatial attention with semantic information: an event coding approach.
AB  - We investigated the influence of conceptual processing on visual attention from
      the standpoint of Theory of Event Coding (TEC). The theory makes two predictions:
      first, an important factor in determining the influence of event 1 on processing
      event 2 is whether features of event 1 are bound into a unified representation
      (i.e., selection or retrieval of event 1). Second, whether processing the two
      events facilitates or interferes with each other should depend on the extent to
      which their constituent features overlap. In two experiments, participants
      performed a visual-attention cueing task, in which the visual target (event 2)
      was preceded by a relevant or irrelevant explicit (e.g., "UP") or implicit (e.g.,
      "HAPPY") spatial-conceptual cue (event 1). Consistent with TEC, we found relevant
      explicit cues (which featurally overlap to a greater extent with the target) and
      implicit cues (which featurally overlap to a lesser extent), respectively,
      facilitated and interfered with target processing at compatible locations.
      Irrelevant explicit and implicit cues, on the other hand, both facilitated target
      processing, presumably because they were less likely selected or retrieved as an
      integrated and unified event file. We argue that such effects, often described as
      "attentional cueing", are better accounted for within the event coding framework.

PMID- 28432448
TI  - Resistance to radial expansion limits muscle strain and work.
AB  - The collagenous extracellular matrix (ECM) of skeletal muscle functions to
      transmit force, protect sensitive structures, and generate passive tension to
      resist stretch. The mechanical properties of the ECM change with age, atrophy,
      and neuromuscular pathologies, resulting in an increase in the relative amount of
      collagen and an increase in stiffness. Although numerous studies have focused on
      the effect of muscle fibrosis on passive muscle stiffness, few have examined how
      these structural changes may compromise contractile performance. Here we combine
      a mathematical model and experimental manipulations to examine how changes in the
      mechanical properties of the ECM constrain the ability of muscle fibers and
      fascicles to radially expand and how such a constraint may limit active muscle
      shortening. We model the mechanical interaction between a contracting muscle and
      the ECM using a constant volume, pressurized, fiber-wound cylinder. Our model
      shows that as the proportion of a muscle cross section made up of ECM increases,
      the muscle's ability to expand radially is compromised, which in turn restricts
      muscle shortening. In our experiments, we use a physical constraint placed around
      the muscle to restrict radial expansion during a contraction. Our experimental
      results are consistent with model predictions and show that muscles restricted
      from radial expansion undergo less shortening and generate less mechanical work
      under identical loads and stimulation conditions. This work highlights the
      intimate mechanical interaction between contractile and connective tissue
      structures within skeletal muscle and shows how a deviation from a healthy, well
      tuned relationship can compromise performance.

PMID- 28432449
TI  - Enteroparasitoses and Toxocarosis Affecting Children from Mar del Plata City,
      Argentina.
AB  - This study evaluated the existence of enteroparasitoses and toxocarosis in
      children of peripheral (PC) and urban communities (UC) from Mar del Plata city
      (Argentina) and their associations with socio-environmental conditions. A
      Parasite Vulnerability Index (PVI) was elaborated using variables such as
      overcrowding, floor type, drinking water source, wastewater disposal, solid waste
      disposal, presence of animals and schooling level. The PC evidenced statistically
      significant higher frequencies of families with high (38.9%) and medium (55.5%)
      PVI, while in the UC low PVI (93%) was the most frequent. A statistically
      significant higher frequency of PC children was parasitized (30.2 vs. 14.5%; chi
      2 Pearson = 5.21; P < 0.05), presented higher parasite frequencies, specific
      richness, parasitic loads, and they also evidenced polyparasitism. The Multiple
      Correspondence Analysis (MCA) showed associations between PC-parasitized
      children, overcrowding and contact with pets and farm animals. The ELISA test to
      the specified determination of Toxocara canis IgG was reactive in a statistically
      significant higher proportion of PC children than the UC (55 vs. 8.5%; chi 2 =
      30.5; P < 0.01). The MCA associated PC reactive children, not adequate hand
      washing, moderate and hypereosinophilia and contact with pets and farm animals.
      Deficient socio-environmental conditions became children more vulnerable to get
      enteroparasitoses and toxocarosis in the PC than in the UC.

PMID- 28432450
TI  - Genetic aberrations and molecular biology of skull base chordoma and
      chondrosarcoma.
AB  - Chordomas and chondrosarcomas are two major malignant bone neoplasms located at
      the skull base. These tumors are rarely metastatic, but can be locally invasive
      and resistant to conventional chemotherapies and radiotherapies. Accordingly,
      therapeutic approaches for the treatment of these tumors can be difficult.
      Additionally, their location at the skull base makes them problematic. Although
      accurate diagnosis of these tumors is important because of their distinct
      prognoses, distinguishing between these tumor types is difficult due to
      overlapping radiological and histopathological findings. However, recent
      accumulation of molecular and genetic studies, including extracranial location
      analysis, has provided us clues for accurate diagnosis. In this report, we review
      the genetic aberrations and molecular biology of these two tumor types. Among the
      abundant genetic features of these tumors, brachyury immunohistochemistry and
      direct sequencing of IDH1/2 are simple and useful techniques that can be used to
      distinguish between these tumors. Although it is still unclear why these tumors,
      which have such distinct genetic backgrounds, show similar histopathological
      findings, comparison of their genetic backgrounds could provide essential
      information.

PMID- 28432451
TI  - Investigating the Use of World Knowledge During On-line Comprehension in Adults
      with Autism Spectrum Disorder.
AB  - The on-line use of world knowledge during reading was examined in adults with
      autism spectrum disorder (ASD). Both ASD and typically developed adults read
      sentences that included plausible, implausible and anomalous thematic relations,
      as their eye movements were monitored. No group differences in the speed of
      detection of the anomalous violations were found, but the ASD group showed a
      delay in detection of implausible thematic relations. These findings suggest that
      there are subtle differences in the speed of world knowledge processing during
      reading in ASD.

PMID- 28432452
TI  - Fluorescent angioscopic imaging of calcium phosphate tribasic: precursor of
      hydroxyapatite, the major calcium deposit in human coronary plaques.
AB  - Coronary calcification is a risk factor for ischemic heart disease.
      Hydroxyapatite that is formed by polymerization from calcium phosphate tribasic
      (CPT) is the major constituent of coronary calcium deposits. If CPT could be
      visualized, coronary calcification could be predicted and prevented. We
      discovered that when CPT and collagen I, the main constituent of collagen fibers,
      are mixed with lac dye (LD) and then exposed to fluorescent light excited at 345
      +/- 15 nm and emitted at 420 nm, a purple fluorescence that is characteristic of
      CPT only is elicited. So, we examined localization of CPT and its relation to
      plaque morphology by color fluorescent angioscopy (CFA) or microscopy (CFM) in 24
      coronary arteries obtained from 12 autopsy subjects. By CFA, the incidence (%) of
      CPT as confirmed by purple fluorescence in 15 normal segments, 25 white plaques,
      14 yellow plaques without necrotic core (NC) and 8 yellow plaques with NC was 20,
      36, 64 and 100 (p < 0.05 vs. normal segments), respectively. By CFM, the CPT was
      either deposited alone amorphously or surrounded hydroxyapatite that was
      identified by Oil Red O, methylene blue and von Kossa's stain. The results
      suggested that CFA using LD is feasible for imaging CPT, that is a precursor of
      hydroxyapatite, in human coronary plaques, and this technique would help
      prediction and discovery of a preventive method of coronary calcification.

PMID- 28432453
TI  - The influence of oxo-bridged binuclear gold(III) complexes on Na/K-ATPase
      activity: a joint experimental and theoretical approach.
AB  - The in vitro effects of oxo-bridged binuclear gold(III) complexes, i.e.,
      [(bipy2Me)2Au2(MU-O)2][PF6]2 (Auoxo6), Au2[(bipydmb-H)2(MU-O)][PF6] (Au2bipyC)
      and [Au2(phen2Me)2(MU-O)2](PF6)2 (Au2phen) on Na/K-ATPase, purified from the
      porcine cerebral cortex, were investigated. All three studied gold complexes
      inhibited the enzyme activity in a concentration-dependent manner achieving IC50
      values in the low micromolar range. Kinetic analysis suggested an uncompetitive
      mode of inhibition for Auoxo6 and Au2bipyC, and a mixed type one for Au2phen.
      Docking studies indicated that the inhibitory actions of all tested complexes are
      related to E2-P enzyme conformation binding to ion channel and intracellular part
      between N and P sub-domain. In addition, Au2phen was able to inhibit the enzyme
      by interacting with its extracellular part as well. Toxic effects of the
      gold(III) complexes were evaluated in vitro by following lactate dehydrogenase
      activity in rat brain synaptosomes and incidence of micronuclei and cytokinesis
      block proliferation index in cultivated human lymphocytes. All investigated
      complexes turned out to induce cytogenetic damage consisting of a significant
      decrease in cell proliferation and an increase in micronuclei in a dose-dependent
      manner. On the other hand, lactate dehydrogenase activity, an indicator of
      membrane integrity/viability, was not affected by Auoxo6 and Au2bipyC, while
      Au2phen slightly modified its activity.

PMID- 28432454
TI  - Cobalt tetradehydrocorrins coordinated by imidazolate-like histidine in the heme
      pocket of horseradish peroxidase.
AB  - Horseradish peroxidase was reconstituted with cobalt tetradehydrocorrin,
      rHRP(Co(TDHC)), as a structural analog of cobalamin coordinated with an
      imidazolate-like His residue, which is generally seen in native enzymes. In
      contrast to the previously reported cobalt tetradehydrocorrin-reconstituted
      myoglobin, rMb(Co(TDHC)), the HRP matrix was expected to provide strong axial
      ligation by His170 which has imidazolate character. rHRP(CoII(TDHC)) was
      characterized by EPR and its reaction with reductants indicates a negative shift
      of its redox potential compared to rMb(Co(TDHC)). Furthermore, aqua- and CN-forms
      of Co(III) state were prepared. The former species was obtained by oxidation of
      rHRP(CoII(TDHC)) with K3[Fe(CN)6]. The cyanide-coordinated Co(III) species in the
      latter was prepared by ligand exchange of rHRP(CoIII(OH)(TDHC)) with exogenous
      cyanide upon addition of KCN. The 13C NMR chemical shift of cyanide in
      rHRP(CoIII(CN)(TDHC)) was determined to be 121.8 ppm. IR measurements show that
      the cyanide of rHRP(CoIII(CN)(TDHC)) has a stretching frequency peak at 2144 cm
      1. The 13C NMR and IR measurements indicate strong coordination of cyanide to
      CoIII(TDHC) relative to rMb(CoIII(CN)(TDHC)). Thus, the extent of pi-back
      donation from the cobalt ion to the cyanide ion is relatively high in
      rHRP(CoIII(CN)(TDHC)). The pK 1/2 values of rHRP(CoIII(OH)(TDHC)) and
      rHRP(CoIII(CN)(TDHC)) are the same (pK 1/2 = 3.2) as determined by a pH titration
      experiment, indicating that cyanide ligation does not affect Co-His ligation,
      whereas cyanide ligation weakens the Co-His ligation in rMb(CoIII(CN)(TDHC)).
      Taken together, these results indicate that HRP reconstituted with cobalt
      tetradehydrocorrin is a suitable cobalamin-dependent enzyme model with
      imidazolate-like His residue.

PMID- 28432456
TI  - Deregulated BCL-2 family proteins impact on repair of DNA double-strand breaks
      and are targets to overcome radioresistance in lung cancer.
AB  - PURPOSE: DNA damage-induced cell death is a major effector mechanism of
      radiotherapy. Aberrant expression of anti-apoptotic BCL-2 family proteins is
      frequently observed in lung cancers. Against this background, we studied
      radioresistance mediated by BCL-2 family proteins at the mechanistic level and
      its potential as target for radiochemotherapy. METHODS: Lung cancer models stably
      expressing BCL-xL or MCL-1 were irradiated to study cell death, clonogenic
      survival, and DNA repair kinetics in vitro, and growth suppression of established
      tumors in vivo. Additionally, endogenous BCL-xL and MCL-1 were targeted by shRNA
      or pharmacologic agents prior to irradiation. RESULTS: Radiation exposure induced
      apoptosis at negligible levels. Yet, anti-apoptotic BCL-xL and MCL-1 expression
      conferred short-term and long-term radioresistance in vitro and in vivo.
      Radioresistance correlated with pertubations in homologous recombination repair
      and repair of DNA double-strand breaks by error-prone, alternative end-joining.
      Notably, genetic or pharmacologic targeting of BCL-xL or MCL-1 effectively
      sensitized lung cancer cells to radiotherapy. CONCLUSIONS: In addition to
      directly suppressing apoptosis, BCL-2 family proteins confer long-term survival
      benefits to irradiated cancer cells associated with utilization of error-prone
      repair pathways. Targeting BCL-xL and MCL-1 is an attractive strategy for
      improving lung cancer radiotherapy.

PMID- 28432457
TI  - Outcome and revision rate of uncemented glenohumeral resurfacing (C.A.P.) after 5
      8 years.
AB  - BACKGROUND: Resurfacing of the glenohumeral joint for patients with glenohumeral
      arthritis has gained popularity since the first introduction. We report the mid
      term results of the Global C.A.P. uncemented resurfacing shoulder prosthesis
      (DePuy Synthes). METHODS: From January 2007 to December 2009, 48 humeral
      cementless resurfacing prostheses in 46 patients were performed. All patients
      were diagnosed with primary glenohumeral osteoarthritis. Patients were contacted
      for review; the Constant Score, visual analog pain scale, Dutch Simple Shoulder
      Test, SF-12 scores and physical examination were assessed both preoperatively and
      yearly postoperatively. Complications and revision surgery were documented.
      Radiographs were evaluated for component size, offset, inclination, height,
      loosening and subluxation. RESULTS: Forty-six patients (12 males) with a mean age
      of 72 years old (range 59-89) were included. At a mean 6.4-year follow-up (range
      5-8), the Constant Score, visual analog pain scale and the Dutch Simple Shoulder
      Test scores improved significantly (p < 0.05) from baseline. Three patients were
      lost to follow-up. One patient died and two patients were not able to attend the
      follow-up appointments, due to other health-related issues. Eleven patients (23%)
      had a revision operation. CONCLUSIONS: The most important findings of this study
      of the Global C.A.P. shoulder resurfacing arthroplasty were an increase of range
      of motion, a reduction of pain complaints, but a concerning high rate of revision
      after mid-term follow-up. LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 28432458
TI  - Is the evaluation of the anterior inferior iliac spine (AIIS) in the AP pelvis
      possible? Analysis of conventional X-rays and 3D-CT reconstructions.
AB  - INTRODUCTION: A hypertrophic AIIS has been identified as a cause for
      extraarticular hip impingement and is classified according to Hetsroni using 3D
      CT reconstructions. The role of the conventional AP pelvis X-ray, which is the
      first standard imaging step for the evaluation of hip pain, has not been
      investigated yet. MATERIALS AND METHODS: AP pelvis X-rays and 3D-CT
      reconstructions of patients were evaluated regarding their morphology of the
      AIIS. The conventional X-rays were categorized into three groups according to the
      projection of the AIIS: above (A) or below (B) the acetabular sourcil or even
      exceeding the anterior acetabular rim (C). They were compared to the morphologic
      types in the 3D-CT reconstruction (Hetsroni type I-III). RESULTS: Ninety patients
      with an equal distribution of type A, B or C projection in the AP pelvis were
      evaluated and compared to the morphology in the 3D-CT reconstruction. The
      projection of the AIIS below the acetabular sourcil (B + C) showed only moderate
      sensitivity (0.76) and specificity (0.64) for a hypertrophic AIIS (Hetsroni type
      II + III), but if the AIIS exceeds the anterior rim, all cases showed a
      hypertrophic AIIS in the 3D-CT reconstructions (Hetsroni type II + III).
      CONCLUSIONS: Distinct differentiation of the AIIS morphology in the AP pelvis is
      not possible, but the projection of the AIIS below the anterior acetabular rim
      represented a hypertrophic AIIS in all cases and should, therefore, be critically
      investigated for a relevant AIIS impingement.

PMID- 28432455
TI  - Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor
      vaccines in murine models of metastatic breast cancer.
AB  - PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost
      antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines
      upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were
      generated from mouse bone marrow or peripheral blood from healthy human donors
      and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9
      agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated
      in BALB/c mice bearing metastatic mammary adenocarcinomas. RESULTS: CpG-DCs
      improved the survival of tumor-bearing mice, reduced the development of lung
      metastases and generated immunological memory. However, dual activation of TLRs
      impaired the efficacy of DC vaccines. In vitro, we found that R848 inhibited CpG
      mediated maturation of murine DCs. A positive feedback loop in TLR9 mRNA
      expression was observed upon CpG stimulation that was inhibited in the presence
      of R848. Impaired activation of NF-kappaB was detected when TLR9 and TLR7 were
      simultaneously activated. Blockade of nitric oxide synthase (NOS) and indoleamine
      pyrrole-2,3-dioxygenase (IDO) improved the activation of CpG-DCs. When we
      evaluated the effect of combined activation of TLR9 and TLR7 in human DCs, we
      found that R848 induced robust DC activation that was inhibited by TLR9 agonists.
      CONCLUSIONS: These observations provide insight in the biology of TLR9 and TLR7
      crosstalk and suggest caution in the selection of agonists for multiple TLR
      stimulation. Blockade of NOS and IDO could improve the maturation of antitumor DC
      vaccines. R848 could prove a useful adjuvant for DC vaccines in human patients.

PMID- 28432459
TI  - Using an anatomically preshaped low-profile locking plate system leads to
      reliable results in comminuted radial head fractures.
AB  - INTRODUCTION: For comminuted and displaced fractures of the radial head open
      reduction and internal fixation (ORIF) is recommended nowadays as the treatment
      of choice. Due to the development of locking plates the possibilities of ORIF in
      complex fracture types were extended. The purpose of this retrospective survey
      therefore was to review the preliminary subjective and objective results in
      patients treated by anatomically preshaped locked plating. A reliable fracture
      healing for these recently introduced plating devices was hypothesized. MATERIALS
      AND METHODS: Subjective and objective criteria included patient's satisfaction,
      pain rating on a visual analogue scale (VAS) and active range of motion (ROM)
      compared to the contralateral armside. Functional scoring included the Morrey
      elbow performance score (MEPS), the QuickDASH and the elbow self-assessment score
      (ESAS). Furthermore, follow-up radiographs were reviewed. RESULTS: Between 2011
      and 2014 a total of 24 patients were managed with ORIF using anatomically
      preshaped low-profile locking plates. All patients had suffered from comminuted
      radial head fractures (type III-IV according to Mason classification). Twenty of
      24 patients returned for follow-up examination after a mean of 30 months (range
      18-53 months). Patients' satisfaction was rated as highly satisfied in 17 cases
      and satisfied in 3 cases. An unrestricted ROM for extension-flexion arc and
      pronation-supination arc was rated in 10 cases. Minor ROM deficiencies with a 5
      degrees  limited extension compared to the contralateral side was evaluated in 6
      cases. Only four patients were rated with and extension and supination deficiency
      of 10 degrees , one of whom with an additional pronation deficiency of 10 degrees
      . The calculated MEPS was O 98 +/- 4 (range 85-100), and the QuickDASH was O 3 +/
      6 (range 0-21). The ESAS was completed by 18 patients with a mean of O 96.54 +/-
      2.95 (range 94-100) indicating a non-restricted elbow function. CONCLUSIONS: The
      treatment of comminuted radial head fractures using anatomically preshaped
      locking radial head plates represents a reliable and safe surgical approach,
      leading to good to excellent functional results. Being aware of the importance of
      the radial head for elbow stability, open reduction and internal fixation should
      be preferred prior to radial head resection or replacement in complex radial head
      fractures. Further trials with a higher number of patients are needed to confirm
      the advantages of preshaped radial head plates.

PMID- 28432460
TI  - 24th International Congress of the European Association for Endoscopic Surgery
      (EAES) Amsterdam, The Netherlands, 15-18 June 2016 : Video Presentations.

PMID- 28432461
TI  - Laparoscopic surgery for T4 colon cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: In colon cancer, T4 stage is still assumed to be a relative
      contraindication for laparoscopic surgery considering the oncological safety. The
      aim of this systematic review with meta-analysis was to evaluate short- and long
      term oncological outcomes after laparoscopic surgery for T4 colon cancer, and to
      compare these with open surgery. METHODS: Using systematic review of literature,
      studies reporting on radicality of resection, disease-free survival (DFS), and/or
      overall survival (OS) after laparoscopic surgery for T4 colon cancer were
      identified, with or without a control group of open surgery. Pooled proportions
      and risk ratios were calculated using an inverse variance method. RESULTS:
      Thirteen observational cohort studies published between 2012 and 2017 were
      included, together consisting of 1217 patients that received laparoscopic surgery
      and 1357 with an open procedure. The proportion of multivisceral resections was
      larger in the open group in five studies. Based on 11 studies, the pooled
      proportion of R0 resection was 0.96 (95% CI: 0.91-0.99) and 0.96 (95% CI: 0.90
      0.98) after laparoscopic and open surgery, respectively. Analysing (mainly) T4a
      subgroups in 6 evaluable studies revealed pooled R0 resection rates of 0.94 in
      both groups. No significant differences were found between laparoscopic and open
      surgery for any survival measure: RR 1.07 (95% CI: 0.96-1.20) for 3-year DFS, RR
      1.04 (95% CI: 0.95-1.15) for 5-year DFS, RR 1.07 (95% CI: 0.99-1.14) for 3-year
      OS, and RR 1.05 (95% CI: 0.98-1.12) for 5-year OS. CONCLUSION: Literature on
      laparoscopic surgery for T4 colon cancer is restricted to non-randomized
      comparisons with substantial allocation bias. Laparoscopic surgery for T4a
      tumours might be safe, whereas for T4b colon cancer requiring multivisceral
      resection it should be applied with caution.

PMID- 28432462
TI  - Novel esophageal stent for treatment of cervical anastomotic leakage after
      esophagectomy.
AB  - BACKGROUND: Dedicated stents for treatment of cervical anastomotic leakage are
      currently unavailable. In this study, we aimed to assess the feasibility and
      efficacy of using custom-designed stents for treatment of cervical anastomotic
      leakage after esophagectomy. METHODS: The stents were designed according to the
      location and size of the leakage and the residual esophageal length as determined
      by esophagography in each case. It had a cup-shaped upper end and a globular
      lower end and a total height of 60-85 mm. The diameter of the upper cup-shaped
      part was 24-26 mm and the length 20-25 mm. The cup part and the stent main body
      were connected at a right angle. Data from cervical anastomotic leakage patients
      treated with these stents were retrospectively analyzed. RESULTS: Data from a
      total of 27 patients with cervical anastomotic leakage were retrospectively
      analyzed. The custom-designed esophageal covered stents were placed successfully
      at the first attempt in 24 cases (88.9%). The total operative time was 5-15 min.
      The stents were removed 7 days to 3 months after leakage healing. Follow-up
      showed no leakage recurrence; three patients had anastomosis scar strictures.
      Fifteen patients died (median survival 13.4 months) and nine survived.
      CONCLUSION: Placement of the novel esophageal covered stent is a minimally
      invasive, efficacious treatment option for the patients with cervical anastomotic
      leakage after esophagectomy.

PMID- 28432464
TI  - Insights into autosomal dominant polycystic kidney disease by quantitative mass
      spectrometry-based proteomics.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic
      disorder that is caused by mutations in the genes PKD1 and PKD2 encoding
      polycystin-1 and polycystin-2, respectively. Polycystin-1 and -2 form a complex,
      interact with several proteins involved in signal transduction and localize to
      discrete subcellular positions, most importantly the primary cilium. Whereas the
      causative mutations leading to ADPKD are known, the underlying deregulated
      cellular pathways are not well understood. In the current review, we introduce
      state-of-the-art mass spectrometry (MS)-based proteomic techniques and summarize
      their use in kidney and ADPKD research. Proteomic profiling approaches, the
      elucidation of ADPKD-relevant protein-protein interactions and the regulation of
      posttranslational modifications are included. We also discuss the use of MS-based
      methods for ADPKD prognosis, diagnosis and disease monitoring by using protein-
      and peptide-based biomarkers.

PMID- 28432463
TI  - Malignant transformation of sinonasal inverted papilloma and related genetic
      alterations: a systematic review.
AB  - Schneiderian papillomas are uncommon tumors which may develop within the nasal
      cavity and comprise three well-defined histological types: sinonasal inverted
      papilloma (SNIP), exophytic papilloma, and oncocytic papilloma. It is well known
      the rate of Schneiderian papilloma may also present a malignant degeneration and
      SNIP represents the most important subgroup in consideration of its frequency and
      malignant propensity. Although HPV infection is always considered the first event
      favoring the development of SNIP, however, it is not established as an eventual
      connection between viral actions and malignant transformation. In fact, different
      molecular mechanisms are suspected to play a crucial role in this process and,
      currently, many authors agree that only by improving our knowledge about these
      mechanisms it will be possible to achieve new and effective targeted therapies.
      So the aim of this study was firstly to systematically review the literature
      focusing on different biomarkers that could be implicated in the stages of SNIP
      malignant degeneration. Secondly, a systematic review with meta-analysis was
      performed to better define the incidence of sinonasal malignancies originating
      from Schneiderian papilloma (SNIP, exophytic papilloma, and oncocytic papilloma).
      Twenty-nine studies comprising a total of 3177 patients were statistically
      analyzed. Results showed a 9% (95% CI = 7-11) overall rate of malignant
      transformation from Schneiderian papilloma. In conclusion, this analysis
      confirmed that the potential malignancy of Schneiderian papilloma should not be
      underestimated. On the other hand, our review showed the paucity of studies
      investigating the molecular alterations which may be related with the malignant
      transformation of SNIP.

PMID- 28432465
TI  - PPARgamma activation regulates lipid droplet formation and lactate production in
      rat Sertoli cells.
AB  - Sertoli cells provide the structural and nutritional support for germ cell
      development; they actively metabolize glucose and convert it to lactate, which is
      an important source of energy for germ cells. Furthermore, Sertoli cells can
      oxidize fatty acids, a metabolic process that is assumed to fulfill their own
      energy requirements. Fatty acids are stored as triacylglycerides within lipid
      droplets. The regulation of fatty acid storage in conjunction with the regulation
      of lactate production may thus be relevant to seminiferous tubule physiology. Our
      aim is to evaluate a possible means of regulation by the PPARgamma activation of
      lipid droplet formation and lactate production. Sertoli cell cultures obtained
      from 20-day-old rats were incubated with Rosiglitazone (10 MUM), a PPARgamma
      activator, for various periods of time (6, 12, 24 and 48 h). Increased
      triacylglycerides levels and lipid droplet content were observed, accompanied by
      a rise in the expression of genes for proteins involved in fatty acid storage,
      such as the fatty acid transporter Cd36, glycerol-3-phosphate-acyltransferases 1
      and 3, diacylglycerol acyltransferase 1 and perilipins 1, 2 and 3, all proteins
      that participate in lipid droplet formation and stabilization. However, PPARgamma
      activation increased lactate production, accompanied by an augmentation in
      glucose uptake and Glut2 expression. These results taken together suggest that
      PPARgamma activation in Sertoli cells participates in the regulation of lipid
      storage and lactate production thereby ensuring simultaneously the energetic
      metabolism for the Sertoli and germ cells.

PMID- 28432466
TI  - Calpain inhibition prevents flotillin re-ordering and Src family activation
      during capacitation.
AB  - Prior to fertilization, mammalian sperm undergo several molecular, biochemical
      and physiological changes in a process termed capacitation. However, the
      mechanisms explaining the involvement of cytoskeletal remodeling and membrane re
      ordering in each process prior to fertilization remain poorly understood. We
      found that the migration of both flotillin microdomains and Src family kinases
      towards the apical ridge of guinea pig sperm occurs under capacitating
      conditions. This re-ordering is associated with spectrin cleavage by calpain.
      Moreover, Src, Fyn, Lyn and Hck interact with flotillin-1; this interaction
      increases in a capacitation-dependent manner and the increased
      autophosphorylation of these kinases is linked to flotillin-1 association. The
      aforementioned results are prevented by the inhibition of calpain by calpeptin.
      Thus, spectrin cytoskeleton cleavage during capacitation seems to precede the
      reorganization of flotillin microdomains and Src family kinases towards the
      apical ridge of the sperm head in order to initiate the signaling cascade
      required for proper capacitation and further acrosome reaction. The significance
      of the Src family kinase reorganization for capacitation is demonstrated by the
      inhibition of calpain during capacitation also preventing the Src-family-kinase
      dependent phosphorylation of FAK at Tyr576/577. Our work further highlights the
      scaffolding properties of flotillin microdomains and reveals the importance of
      their large-scale segregation during capacitation.

PMID- 28432467
TI  - Renal-skin syndromes.
AB  - Renal-skin syndroms are a group of genetic disorders with renal and cutaneous
      manifestations that target molecular components present in both organs. Inherited
      renal-skin syndromes are mainly associated with defects of cell-matrix adhesion.
      We provide a non-exhaustive overview of the main molecular players at cell-matrix
      adhesions in mouse models and in human genetic disorders affecting kidney and
      skin. Renal and urinary tract involvement is described in all four major
      epidermolysis bullosa types and, in particular, in junctional subtypes and in
      recessive dystrophic epidermolysis bullosa. Here, we describe in detail those
      subtypes for which reno-urinary involvement is a constant and primary feature.
      Furthermore, complex multiorgan disorders with a predisposition to malignancies
      or attributable to metabolic defects that involve both kidney and skin are
      briefly summarized.

PMID- 28432468
TI  - Population pharmacokinetics of intravenous acetaminophen in Japanese patients
      undergoing elective surgery.
AB  - INTRODUCTION: Intravenous (i.v.) acetaminophen is administered during surgery for
      postoperative analgesia. However, little information is available on the
      pharmacokinetics of i.v. acetaminophen in Japanese patients undergoing surgery
      under general anesthesia. METHODS: The study was approved by the Institutional
      Review Board and registered at UMIN-CTR (UMIN000013418). Patients scheduled to
      undergo elective surgery under general anesthesia were enrolled after obtaining
      written informed consent. During surgery, 1 g of i.v. acetaminophen was
      administered over 15, 60, or 120 min. Acetaminophen concentrations (15 or 16
      samples per case) were measured at time points from 0-480 min after the start of
      administration (liquid chromatography-mass spectrometry/tandem mass spectrometry;
      limit of quantitation 0.1 MUg/mL). The predictive performance of three published
      pharmacokinetic models was evaluated. Population pharmacokinetics were also
      analyzed using a nonlinear mixed-effect model based on the NONMEM program.
      RESULTS: Data from 12 patients who underwent endoscopic or lower limb procedures
      were analyzed (male/female = 7/5, median age 55 years, weight 63 kg). Anesthesia
      was maintained with remifentanil and propofol or sevoflurane. The pharmacokinetic
      model of i.v. acetaminophen reported by Wurthwein et al. worked well. Using 185
      datapoints, the pharmacokinetics of i.v. acetaminophen were described by a two
      compartment model with weight as a covariate but not age, sex, or creatinine
      clearance. The median prediction error and median absolute prediction error of
      the final model were -1 and 10%, respectively. CONCLUSION: A population
      pharmacokinetic model of i.v. acetaminophen in Japanese patients was constructed,
      with performance within acceptable ranges.

PMID- 28432469
TI  - Renal findings in patients with Mulibrey nanism.
AB  - BACKGROUND: Mulibrey nanism (MUL) is a rare inherited disease caused by genetic
      defects affecting peroxisomal TRIM37 protein. MUL affects multiple organs,
      leading to growth retardation and early onset type 2 diabetes. We aimed to
      characterize the structure and function of kidneys and the urinary tract in a
      large cohort of Finnish MUL patients. METHODS: Ultrasound, magnetic resonance
      imaging (MRI), and autopsy findings of the kidneys and urinary tract from 101 MUL
      patients were retrospectively analyzed. Renal function was examined using blood
      and urine biochemistry. Kidney pathology was assessed by histology and
      immunohistochemistry from biopsy and autopsy samples. RESULTS: Structural
      anomalies of the kidneys and urinary tract were found in 13 % of MUL patients and
      renal tumors and macroscopic cystic lesions in 14 % and 43 % respectively.
      Overall, kidney histology was well preserved, but glomerular cysts with a wide
      Bowman's space were observed in most samples (87 %). Also, prominent and abundant
      blood vessels with thick walls were typically seen. Expression of endothelial
      cell markers and angiogenic growth factors PDGF-B and FGF1 (but not VEGF-A) was
      significantly increased in MUL kidneys. Markers of fibrosis and epithelial
      mesenchymal transformation, alpha-SMA, and vimentin were moderately up-regulated.
      Despite radiological and histological changes, most MUL patients (age 0.2-51
      years) had normal kidney function. However, 9 out of 36 patients (25 %) had
      hypertension and 6 out of 26 (23 %) had mildly decreased glomerular filtration.
      CONCLUSIONS: Genetic defects in the TRIM37 gene lead to an increased risk for
      kidney anomalies, renal tumors, and solitary cysts in addition to glomerular
      cystic lesions, but not to progressive deterioration of renal function.

PMID- 28432470
TI  - Male behavioural plasticity depends on maternal mating status in the two-spotted
      spider mite.
AB  - In haplodiploid organisms including the two-spotted spider mite, Tetranychus
      urticae (Acari: Tetranychidae), both unmated and mated females can produce male
      offspring. A previous study reported that males produced by unmated females (UM
      males) find pre-reproductive females more quickly than males produced by mated
      females (M males) in T. urticae. However, it remains unclear what factors cause
      the difference. We investigated effects of maternal mating status on mate
      searching behaviour of their sons by changing the sons' developmental
      environment. In T. urticae, the primary sex ratio of mated-female colonies is
      female-biased. For both UM and M males, half of individuals were reared with
      males to imitate unmated-female colonies, whereas the rest were reared with
      females to imitate mated-female colonies. In UM males, individuals that had
      developed with males found pre-reproductive females more quickly than those that
      had developed with females. However, such a difference was not observed in M
      males. This indicates that behavioural response to the developmental environment
      differs between UM and M males. It means that the behavioural plasticity depends
      on maternal mating status. When males were individually reared, however, there
      was no significant difference in the mate-searching behaviour between UM and M
      males, indicating that maternal mating status does not independently affect their
      sons' mate-searching behaviour. This study showed that male mate-searching
      behaviour is changed by their developmental environment and maternal mating
      status. This behavioural plasticity depending on maternal mating status is the
      first reported in haplodiploid organisms.

PMID- 28432472
TI  - Anti-Infective and Anti-Inflammatory Pharmacotherapies.
AB  - Ocular infection and inflammation are common and are associated with myriad
      ocular conditions ranging from mild disease to blinding conditions. There are
      numerous anti-invectives with spectra against inciting pathogens. Given the
      potential for ocular infections to rapidly progress initial broad spectrum
      therapy is usually required, with therapy tailored as microbiological
      identification and sensitivities become available. The emergence of antibiotic
      resistance has become a major health problem. Anti-inflammatory therapy can be
      institutes to prevent ocular symptoms and end-organ damage. A therapy should be
      selected which is potent enough to interrupt the inflammatory cascades in play,
      but which avoids potential side effects. Glucocorticoids, NSAIDs, and biological
      agents may be used singularly or in combination. New drug delivery devices may
      allow for better local treatment of chronic ocular inflammation.

PMID- 28432471
TI  - Differentiating Middle Ear and Medial Olivocochlear Effects on Transient-Evoked
      Otoacoustic Emissions.
AB  - The response of the inner ear is modulated by the middle ear muscle (MEM) and
      olivocochlear (OC) efferent systems. Both systems can be activated reflexively by
      acoustic stimuli delivered to one or both ears. The acoustic middle ear muscle
      reflex (MEMR) controls the transmission of acoustic signals through the middle
      ear, while reflex activation of the medial component of the olivocochlear system
      (the MOCR) modulates cochlear mechanics. The relative prominence of the two
      efferent systems varies widely between species. Measuring the effect of either of
      these systems can be confounded by simultaneously activating the other. We
      describe a simple, sensitive online method that can identify the effects both
      systems have on otoacoustic emissions (OAEs) evoked by transient stimuli such as
      clicks or tone pips (TEOAEs). The method detects directly in the time domain the
      changes in the stimulus and/or emission pressures caused by contralateral noise.
      Measurements in human participants are consistent with other reports that the
      threshold for MOCR activation is consistently lower than for MEMR. The method
      appears to control for drift and subject-generated noise well enough to avoid the
      need for post hoc processing, making it promising for application in animal
      experiments (even if awake) and in the hearing clinic.

PMID- 28432473
TI  - Vasopressin and Vasopressin Antagonists in Heart Failure.
AB  - Despite the introduction of multiple new pharmacological agents over the past
      three decades in the field of heart failure (HF), overall prognosis remains poor.
      Hyponatremia is prevalent in HF patients and has been suggested as a contributor
      to poor response to standard therapy. Elevated levels of arginine vasopressin
      (AVP), a peptide hormone produced in the hypothalamus, play a role in development
      of hyponatremia, and AVP and its surrogate, copeptin, are related to changes in
      osmolality, hemodynamics, neuro-hormones as well as in overall outcome in HF
      patients. Of current pharmacological interest are the selective and non-selective
      vasopressin receptor antagonists (VRAs), which inhibit vasoconstriction and
      cardiac remodeling mediated by the V1a receptors in smooth blood vessels, and
      water retention (increased urine osmolality and decreased water excretion) by
      increasing aquaporin-2 water channels mediated by the V2 receptors in the renal
      collecting tubules. The optimal use of VRAs is yet to be determined, especially
      in patients with congestive HF. Although long-term effects on improvement in
      mortality have not been shown in the Efficacy of Vasopressin Antagonism in Heart
      Failure Outcome Study with Tolvaptan (EVEREST) trial, the only long-term outcome
      trial to date, many short-term studies indicate beneficial aquaretic- and
      hemodynamic-effects of the VRAs. In contrast to loop diuretics, these new agents
      tend to increase urine flow and the excretion of electrolyte-free water (so
      called aquaresis) in patients with HF, without substantial changes in sodium or
      potassium excretion. This chapter reviews the role of AVP and copeptin in HF, and
      the treatment potential of VRAs in HF.

PMID- 28432474
TI  - Have group A and B streptococcal infections become neglected diseases in Europe?

PMID- 28432475
TI  - A Shinella beta-N-acetylglucosaminidase of glycoside hydrolase family 20 displays
      novel biochemical and molecular characteristics.
AB  - beta-N-Acetylglucosaminidases (GlcNAcases) are important for many biological
      functions and industrial applications. In this study, a glycoside hydrolase
      family 20 GlcNAcase from Shinella sp. JB10 was expressed in Escherichia coli BL21
      (DE3). Compared to many GlcNAcases, the purified recombinant enzyme (rJB10Nag)
      exhibited a higher specificity activity (538.8 umol min-1 mg-1) or V max (1030.0
      +/- 82.1 umol min-1 mg-1) toward p-nitrophenyl beta-N-acetylglucosaminide and
      N,N'-diacetylchitobiose (specificity activity of 35.4 umol min-1 mg-1) and a
      higher N-acetylglucosaminide tolerance (approximately 50% activity in 70.0 mM N
      acetylglucosaminide). The degree of synergy on enzymatic degradation of chitin by
      a commercial chitinase and rJB10Nag was as high as 2.35. The enzyme was tolerant
      to most salts, especially 3.0-15.0% (w/v) NaCl and KCl. These biochemical
      characteristics make the JB10 GlcNAcase a candidate for use in many potential
      applications, including processing marine materials and the bioconversion of
      chitin waste. Furthermore, the enzyme has the highest proportions of alanine
      (16.5%), glycine (10.5%), and random coils (48.8%) with the lowest proportion of
      alpha-helices (24.9%) among experimentally characterized GH 20 GlcNAcases from
      other organisms.

PMID- 28432476
TI  - Immunological Mechanisms of Adsorptive Cytapheresis in Inflammatory Bowel
      Disease.
AB  - Ulcerative colitis and Crohn's disease are the two main forms of inflammatory
      bowel disease (IBD). The study of immunological pathways involved in the onset of
      IBD is of fundamental importance to identify potential biological markers of
      disease activity and specific targets for therapy. Removing excess and activated
      circulating leukocytes with adsorptive cytapheresis has been shown to be a
      potentially effective treatment for patients with an inflamed bowel. Adsorptive
      cytapheresis is a non-pharmacological approach for active IBD, in which known
      sources of inflammatory cytokines such as activated myeloid lineage leucocytes
      are selectively depleted from the circulatory system. The decrease in
      inflammatory load caused by removing these cells is thought to enhance drug
      therapy and thereby promote disease remission. The benefit of cytapheresis
      appears to rest upon its ability to reduce levels of certain immune cell
      populations; however, whether this depletion results in further changes in
      lymphocyte populations and cytokine production needs further clarification. In
      this review, we aim to summarize existing evidence on the role of cytapheresis in
      patients with IBD, its effect on cytokine levels and cellular populations, and to
      discuss its potential impact on disease activity.

PMID- 28432477
TI  - Usefulness of Non-magnifying Narrow Band Imaging in EVIS EXERA III Video Systems
      and High-Definition Endoscopes to Diagnose Dysplasia in Barrett's Esophagus Using
      the Barrett International NBI Group (BING) Classification.
AB  - BACKGROUND: Narrow band imaging (NBI) allows identification of abnormal areas of
      Barrett's esophagus (BE) and could facilitate targeted biopsies. AIMS: We
      evaluated the diagnostic accuracy for dysplasia prediction using non-magnifying
      NBI in Evis Exera III processors and high-definition endoscopes using the Barrett
      International NBI Group (BING) classification, as well as inter/intraobserver
      agreement for dysplasia prediction and mucosal/vascular patterns. METHODS: Eight
      observers (4 staff endoscopists and 4 trainee endoscopists) evaluated 100 images
      selected from an anonymized bank of 470 photographs using the BING
      classification. Observers were to assign their individual assessment of the
      mucosal and vascular pattern, and prediction for dysplasia. Accuracy for
      dysplasia prediction and intra/interobserver agreement was calculated. RESULTS:
      Dysplasia prediction had an accuracy of 81.1%, sensitivity of 48.4%, and a
      specificity of 91%. Positive predictive value and negative predictive value (NPV)
      were 61.4 and 85.5%, respectively. Dysplasia prediction done with a high degree
      of confidence (vs. low degree of confidence) had better diagnostic accuracy (85.8
      vs. 70.7%). Interobserver concordance for dysplasia was weak: Kappa = 0.40.
      Agreement for mucosal and vascular patterns was 0.39 and 0.30, respectively.
      Intraobserver concordance (assessed 6 months after initial test) for mucosal
      pattern, vascular pattern, and dysplasia prediction was moderate: Kappa = 0.56,
      Kappa = 0.47 and Kappa = 0.60, respectively. CONCLUSIONS: Our results showed that
      NBI had a significant accuracy in BE assessment for dysplasia prediction, high
      specificity (>90%), and NPV (>85%), with suboptimal sensitivity. NBI could be a
      useful additional tool for BE inspection and targeted biopsies, but cannot avoid
      the need for biopsies following the Seattle protocol.

PMID- 28432478
TI  - The Arabidopsis splicing factors, AtU2AF65, AtU2AF35, and AtSF1 shuttle between
      nuclei and cytoplasms.
AB  - KEY MESSAGE: The Arabidopsis splicing factors, AtU2AF65, AtU2AF35, and AtSF1
      shuttle between nuclei and cytoplasms. These proteins also move rapidly and
      continuously in the nuclei, and their movements are affected by ATP depletion.
      The U2AF65 proteins are splicing factors that interact with SF1 and U2AF35
      proteins to promote U2snRNP for the recognition of the pre-mRNA 3' splice site
      during early spliceosome assembly. We have determined the subcellular
      localization and movement of these proteins' Arabidopsis homologs. It was found
      that Arabidopsis U2AF65 homologs, AtU2AF65a, and AtU2AF65b proteins interact with
      AtU2AF35a and AtU2AF35b, which are Arabidopsis U2AF35 homologs. We have examined
      the mobility of these proteins including AtSF1 using fluorescence recovery after
      photobleaching and fluorescence loss in photobleaching analyses. These proteins
      displayed dynamic movements in nuclei and their movements were affected by ATP
      depletion. We have also demonstrated that these proteins shuttle between nuclei
      and cytoplasms, suggesting that they may also function in cytoplasm. These
      results indicate that such splicing factors show very similar characteristics to
      their human counterparts, suggesting evolutionary conservation.

PMID- 28432479
TI  - Pharmacokinetics and efficacy of an ivermectin implant for long-term prevention
      of Dirofilaria immitis infection in dogs.
AB  - An exploratory study was carried out to assess the in vivo efficacy of different
      prototypes of subcutaneous implants containing ivermectin (IVM) for the
      prevention of canine Dirofilaria immitis infection. The implants consisted of an
      ethylcellulose matrix containing IVM (3.0, 4.5, and 6.0 mg/implant; from 0.29 to
      0.63 mg/kg bw) as active ingredient designed to release approximately 0.1 ng of
      IVM/mL in the plasma for at least 12 months. Six dogs were implanted on day -365.
      On day -12, three heartworm-free dogs were included in the study as a control
      group. All nine dogs were examined on day -7 and day 0 for circulating D. immitis
      microfilariae and by an antigen ELISA kit to confirm that the dogs were heartworm
      free. The dogs were artificially infected with 75 D. immitis infective larvae
      (L3) each on day 0. Dogs in the control group were humanely euthanized on day 153
      to verify the infectivity of the larvae, while implanted dogs were further
      examined for circulating D. immitis microfilariae and antigen on days 153, 195,
      and 246. The treated dogs were not necropsied. The pharmacokinetic profile of the
      IVM implant was assessed in plasma samples taken on day -364, then at different
      times until the infection day, and again on days, 15, 30, 60, 90, 120, and 153.
      Throughout the study, body weights were measured during clinical examination on
      days 0, 30, 60, 90, 120, and 153. At necropsy, all control dogs were found
      infected, each with 10-11 adult heartworms. Implanted dogs were negative at both
      microfilaria and D. immitis antigen examinations until day 246 (8 months from the
      infection). IVM plasma levels ranged 0.06-0.16 ng/mL on day 0 and remained stable
      until day 60, afterward they gradually decreased under the limit of
      quantification of the method. Throughout the study, no side effect was observed.
      On the basis of these results, it was possible to conclude that the different
      prototypes of implants were able to protect the dogs from D. immitis artificial
      infection for at least 12 months.

PMID- 28432480
TI  - Predictive Value of 18F-FDG PET/CT for Axillary Lymph Node Metastasis in Invasive
      Ductal Breast Cancer.
AB  - BACKGROUND: This study assessed whether primary tumor maximum standardized uptake
      value (pSUVmax) measured by 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron
      emission tomography/computed tomography (PET/CT) could improve the prediction of
      axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC).
      METHODS: In this study, 128 IDC patients who underwent pretreatment 18F-FDG
      PET/CT and surgical resection of primary tumor with sentinel lymph node biopsy,
      ALN dissection, or both were analyzed. All the patients were classified as five
      molecular subtypes. The optimal cutoff values of pSUVmax for all the patients and
      each molecular subtype for the prediction of ALN metastasis were determined using
      receiver operating characteristic (ROC) analysis. Furthermore, the prognostic
      accuracy of ALN metastasis was assessed using c-statistics. RESULTS: The findings
      showed ALN metastasis in 52 patients (40.6%). The 18F-FDG PET/CT procedure had a
      sensitivity of 48.1% and a specificity of 94.7% for ALN metastasis. In the ROC
      analysis of pSUVmax for ALN metastasis, the optimal cutoff value was 3.9 for all
      the patients, 2.8 for the luminal A subtype, 3.3 for the luminal B (human
      epidermal growth factor receptor 2 [HER2]-negative) subtype, 5.3 for the luminal
      B (HER2-positive) subtype, 12.7 for the HER2-positive subtype, and 11.5 for the
      triple-negative subtype. A predictive ALN metastasis model using nodal 18F-FDG
      uptake finding gave a c-statistic of 0.714, and a model combination of nodal 18F
      FDG uptake finding with pSUVmax of all the patients gave a c-statistic of 0.736
      (P = 0.3926). However, the combination of nodal the 18F-FDG uptake finding with
      the pSUVmax of each molecular subtype gave a c-statistic of 0.791 (P = 0.0047).
      CONCLUSIONS: Combining the pSUVmax of each molecular subtype with the nodal 18F
      FDG uptake finding can improve the prediction of ALN metastasis in IDC.

PMID- 28432481
TI  - The Pretreatment Neutrophil-to-Lymphocyte Ratio is a Prognostic Determinant of T3
      4 Hypopharyngeal Squamous Cell Carcinoma.
AB  - OBJECTIVE: This study aimed to investigate the clinicopathological factors that
      influence recurrence and survival in patients who undergo operations for T3-4
      hypopharyngeal squamous cell carcinomas (SCCs). MATERIALS AND METHODS: One
      hundred and five patients who underwent surgery between 2001 and 2008 for
      advanced hypopharyngeal SCCs were consecutively enrolled and reviewed. RESULTS:
      The pretreatment neutrophil-to-lymphocyte ratio (NLR; median 3.22, range 0.62
      46.50) was associated with disease recurrence and patient survival. A difference
      in the 5-year cumulative disease recurrence rate between patients with high
      (>=3.22) and low (<3.22) NLRs was significant (60.4 and 36.5%, respectively; p =
      0.004). A multivariate analysis confirmed that an NLR >=3.22 was an independent
      indicator of a poor prognosis for advanced hypopharyngeal SCC, as per the
      following parameters: overall survival (hazard ratio [HR] 2.53, 95% confidence
      interval [CI] 1.48-4.30, p = 0.001), disease-specific survival (HR 2.45, 95% CI
      1.38-4.34, p = 0.002), and disease-free survival (HR 2.18, 95% CI 1.24-3.83, p =
      0.007). Additional prognostic factors per the survival analyses included lymph
      node density, surgical margin, lymphovascular invasion, and perineural invasion.
      CONCLUSIONS: An NLR >=3.22 is associated with a higher risk of disease recurrence
      and poor survival in patients with T3-4 hypopharyngeal SCCs. We propose the use
      of the NLR to broaden the current TNM staging system; the development of a more
      effective treatment protocol for patients with high NLRs will be essential.

PMID- 28432482
TI  - The sensible health care professional: a care ethical perspective on the role of
      caregivers in emotionally turbulent practices.
AB  - This article discusses the challenging context that health care professionals are
      confronted with, and the impact of this context on their emotional experiences.
      Care ethics considers emotions as a valuable source of knowledge for good care.
      Thinking with care ethical theory and looking through a care ethical lens at a
      practical case example, the authors discern reflective questions that (1) shed
      light on a care ethical approach toward the role of emotions in care practices,
      and (2) may be used by practitioners and facilitators for care ethical reflection
      on similar cases, in the particular and concrete context where issues around
      emotional experiences arise. The authors emphasize the importance of allowing
      emotions to exist, to acknowledge them and to not repress them, so that they can
      serve as a vehicle for ethical behavior in care practices. They stress the
      difference between acknowledging emotions and expressing them limitlessly.
      Formational practices and transformational research practices are being proposed
      to create moral space in care institutions and to support health care
      professionals to approach the emotionally turbulent practices they encounter in a
      way that contributes to good care for all those involved.

PMID- 28432483
TI  - What's in a gold standard? In defence of randomised controlled trials.
AB  - The standardised randomised clinical trial (RCT) has been exceedingly popular in
      medical research, economics, and practical policy making. Recently, RCTs have
      faced criticism. First, it has been argued by John Worrall that we cannot be
      certain that our sample is not atypical with regard to possible confounding
      factors. I will argue that at least in the case of medical research, we know
      enough about the relevant causal mechanisms to be justified to ignore a number of
      factors we have good reason not to expect to be disruptive. I will also argue
      against an argument provided by Nancy Cartwright and Eileen Munro that RCTs
      should not be taken to deductively infer probabilistic causal claims, but
      ampliatively. The paper will end on a discussion of evidence hierarchies and a
      defence of the stance of evidence-based medicine that RCTs are the best available
      method to assess a treatment's efficacy.

PMID- 28432484
TI  - Complete mitochondrial genome sequences of Korean native horse from Jeju Island:
      uncovering the spatio-temporal dynamics.
AB  - The Korean native horse (Jeju horse) is one of the most important animals in
      Korean historical, cultural, and economical viewpoints. In the early 1980s, the
      Jeju horse was close to extinction. The aim of this study is to explore the
      phylogenomics of Korean native horse focusing on spatio-temporal dynamics. We
      determined complete mitochondrial genome sequences for the first Korean native (n
      = 6) and additional Mongolian (n = 2) horses. Those sequences were analyzed
      together with 143 published ones using Bayesian coalescent approach as well as
      three different phylogenetic analysis methods, Bayesian inference, maximum
      likelihood, and neighbor-joining methods. The phylogenomic trees revealed that
      the Korean native horses had multiple origins and clustered together with some
      horses from four European and one Middle Eastern breeds. Our phylogenomic
      analyses also supported that there was no apparent association between breed or
      geographic location and the evolution of global horses. Time of the most recent
      common ancestor of the Korean native horse was approximately 13,200-63,200 years,
      which was much younger than 0.696 My of modern horses. Additionally, our results
      showed that all global horse lineages including Korean native horse existed prior
      to their domestication events occurred in about 6000-10,000 years ago. This is
      the first study on phylogenomics of the Korean native horse focusing on spatio
      temporal dynamics. Our findings increase our understanding of the domestication
      history of the Korean native horses, and could provide useful information for
      horse conservation projects as well as for horse genomics, emergence, and the
      geographical distribution.

PMID- 28432485
TI  - Persistent Impairment of T-Cell Regeneration in a Patient with Activated PI3K
      delta Syndrome.

PMID- 28432488
TI  - Editorial for clinical investigations: toward the vision and spirit of CARS with
      innovative clinical investigations.

PMID- 28432487
TI  - Sodium-Hydrogen-Exchanger expression in human sperm and its relationship with
      semen parameters.
AB  - PURPOSE: Sperm-specific sodium-hydrogen exchanger (sNHE) is essential to maintain
      sperm normal function in mice; however, its role in human sperm has not been
      clarified to date. The aim of this study is to investigate the expression pattern
      of sNHE in human spermatozoa and its relationship with sperm functional
      parameters. METHOD: Semen samples from 68 asthenozoospermic and 61
      normozoospermic men were analyzed for sperm concentration, motility, and acrosome
      reaction, and high motile spermatozoa were collected by swim-up method. The
      expression of sNHE in spermatozoa was detected by Western blot and
      immunofluorescence staining. The relationship between sNHE expression and sperm
      parameters was assessed. RESULTS: We identified sNHE is mainly localized to the
      principal piece of the human sperm tail. The expression of sNHE was positively
      correlated with sperm concentration, total number, and progressive motility.
      Moreover, sNHE expression was upregulated in swim-up sperm and associated with
      most of sperm motility parameters including straight line velocity and
      curvilinear velocity. Our results also showed that sNHE expression is decreased
      in sperm from patients with asthenozoospermia compared with that from normal
      controls. However, no correlation was found between sNHE expression and acrosome
      reaction in spermatozoa. CONCLUSIONS: The expression pattern of sNHE suggested
      that this protein may be involved in the regulation of sperm motility, and
      aberration of its expression in sperm may contribute to the pathogenesis of
      asthenozoospermia.

PMID- 28432486
TI  - Cholesterol as a modifying agent of the neurovascular unit structure and function
      under physiological and pathological conditions.
AB  - The brain, demanding constant level of cholesterol, precisely controls its
      synthesis and homeostasis. The brain cholesterol pool is almost completely
      separated from the rest of the body by the functional blood-brain barrier (BBB).
      Only a part of cholesterol pool can be exchanged with the blood circulation in
      the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and
      24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and
      neuroglia, constituting neurovascular unit (NVU), are crucial for the brain
      cholesterol metabolism and undergo precise regulation by numerous modulators,
      metabolites and signal molecules. In physiological conditions maintaining the
      optimal cholesterol concentration is important for the energetic metabolism,
      composition of cell membranes and myelination. However, a growing body of
      evidence indicates the consequences of the cholesterol homeostasis dysregulation
      in several pathophysiological processes. There is a causal relationship between
      hypercholesterolemia and 1) development of type 2 diabetes due to long-term high
      fat diet consumption, 2) significance of the oxidative stress consequences for
      cerebral amyloid angiopathy and neurodegenerative diseases, 3) insulin resistance
      on progression of the neurodegenerative brain diseases. In this review, we
      summarize the current state of knowledge concerning the cholesterol influence
      upon functioning of the NVU under physiological and pathological conditions.

PMID- 28432489
TI  - Design, development and clinical validation of computer-aided surgical simulation
      system for streamlined orthognathic surgical planning.
AB  - PURPOSE: There are many proven problems associated with traditional surgical
      planning methods for orthognathic surgery. To address these problems, we
      developed a computer-aided surgical simulation (CASS) system, the
      AnatomicAligner, to plan orthognathic surgery following our streamlined clinical
      protocol. METHODS: The system includes six modules: image segmentation and three
      dimensional (3D) reconstruction, registration and reorientation of models to
      neutral head posture, 3D cephalometric analysis, virtual osteotomy, surgical
      simulation, and surgical splint generation. The accuracy of the system was
      validated in a stepwise fashion: first to evaluate the accuracy of
      AnatomicAligner using 30 sets of patient data, then to evaluate the fitting of
      splints generated by AnatomicAligner using 10 sets of patient data. The
      industrial gold standard system, Mimics, was used as the reference. RESULT: When
      comparing the results of segmentation, virtual osteotomy and transformation
      achieved with AnatomicAligner to the ones achieved with Mimics, the absolute
      deviation between the two systems was clinically insignificant. The average
      surface deviation between the two models after 3D model reconstruction in
      AnatomicAligner and Mimics was 0.3 mm with a standard deviation (SD) of 0.03 mm.
      All the average surface deviations between the two models after virtual osteotomy
      and transformations were smaller than 0.01 mm with a SD of 0.01 mm. In addition,
      the fitting of splints generated by AnatomicAligner was at least as good as the
      ones generated by Mimics. CONCLUSION: We successfully developed a CASS system,
      the AnatomicAligner, for planning orthognathic surgery following the streamlined
      planning protocol. The system has been proven accurate. AnatomicAligner will soon
      be available freely to the boarder clinical and research communities.

PMID- 28432491
TI  - Anti-Biofilm Activity of Polyazolidinammonium Modified with Iodine Hydrate Ions
      against Microbial Biofilms of Uropathogenic Coliform Bacteria.
AB  - The dynamics of microbial biofilm formation by standard strain and by clinical
      strains of uropathogenic coliform bacteria was investigated in vitro and the
      effect of sublethal concentrations of the polymer compound polyazolidinammonium
      modified with iodine hydrate ions on the initial stages of biofilm formation was
      assessed. Treatment of immunological plate wells with the polymeric compound
      prevented film formation, especially in case of clinical E. coli strain carrying
      FimH virulence gene.

PMID- 28432490
TI  - Thallium-201 washout rate of stress myocardial perfusion imaging as a predictor
      of mortality in diabetic kidney disease patients initiating hemodialysis: an
      observational, follow-up study.
AB  - BACKGROUND: Thallium-201 washout rate of stress myocardial perfusion imaging
      (MPI) has been reported to correlate with coronary flow reserve which is a
      parameter of myocardial microcirculation. However, the evidence for its use in
      diabetic kidney disease (DKD) has been lacking, and the association between
      thallium-201 washout rate and adverse outcomes including death is unknown.
      Therefore, the present study was conducted to evaluate the predictive ability of
      thallium-201 washout rate for mortality in DKD patients initiating hemodialysis.
      METHODS: A total of 96 patients with type 2 diabetes who had been started on
      maintenance hemodialysis undergoing stress MPI with thallium-201 within 1 year,
      72 men and 24 women, with a median age of 67 years, were studied. The endpoint
      was defined as all-cause death. The Cox proportional hazards model was used to
      calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: During
      the mean follow-up period of 3.4 +/- 2.1 years, 18 (18.8%) deaths occurred.
      Cumulative survival rates during the follow-up period, with thallium-201 washout
      rate levels in the lowest tertile (3.1-36.2%), the middle tertile (36.5-46.3%),
      and the highest tertile (46.4-66.2%), were 51.0, 86.5, and 85.3%, respectively.
      Overall, the multivariate Cox regression analysis revealed that thallium-201
      washout rate remained an independent predictor of death after adjusting by
      confounding variables (HR 0.91, 95% CI 0.85-0.97). CONCLUSIONS: Among DKD
      patients initiating hemodialysis, thallium-201 washout rate seems to be useful
      for predicting death.

PMID- 28432492
TI  - Effect of Anti-Norepinephrine Antibodies on the Development of Neuropathic Pain.
AB  - The study focuses on induction of autoantibodies directed against
      neurotransmitter norepinephrine during neuropathic pain syndrome and on the
      effect of immunization with norepinephrine-protein conjugated antigen on the
      development of this syndrome. The formation of anti-norepinephrine antibodies
      aggravated and prolonged neuropathic pain.

PMID- 28432493
TI  - Effect of Pharmacological Modulation of Activity of Metabotropic Glutamate
      Receptors on Their Gene Expression after Excitotoxic Damage in Hippocampal
      Neurons.
AB  - Microinjection of kainic acid into rat hippocampus causes excitotoxic neuronal
      damage predominantly in the CA3 and CA1 fields. These lesions can be
      significantly reduced by simultaneous administration of MPEP, a negative
      allosteric modulator of type 5 metabotropic glutamate receptors, and LY354740, an
      agonist of type 2 metabotropic glutamate receptors. The decrease in neuronal
      death in the hippocampus during pharmacological modulation was paralleled by
      adaptive changes in gene expression. In the hippocampus, gene expression of type
      5 postsynaptic metabotropic glutamate receptor was close to the control level,
      and in the frontal cortex expression of the gene of alpha1-subunit of the GABAA
      receptor returned to normal. In the frontal cortex, a reciprocal relationship was
      observed for type 2 metabotropic glutamate receptor: expression of the
      corresponding gene decreased in response to pharmacological activation.

PMID- 28432494
TI  - Primary prevention and screening practices among long-term breast cancer
      survivors.
AB  - PURPOSE: Parallel to increasing survival of breast cancer (BC) patients, a need
      has arisen to characterize the follow-up required to improve and maintain their
      health. Our study aimed to assess changes in lifestyle habits over time among the
      study population, compare compliance rates of selected primary and secondary
      prevention practices between long-term BC survivors and an age-matched comparison
      group, and identify factors associated with compliance to these practices.
      METHODS: The study population comprised 250 Israeli BC survivors, diagnosed with
      BC between 1999 and 2003, without evidence of disease after 8-12 years, and 250
      women with no cancer history, individually matched to survivors by age and area
      of residence. Data collection and analysis were conducted during August 2012-June
      2015 and included socio-demographic variables, lifestyle habits, health promotion
      by the family physician, and participation in screening procedures and prevention
      measures. RESULTS: Higher performance rates of mammography and colonoscopy among
      BC survivors were observed, as well as a greater likelihood of receiving an
      influenza vaccine and undergoing a bone mineral density scan (adjusted-ORs: 7.7,
      1.48, 1.42, and 2.59, respectively) compared to controls. Factors identified with
      compliance to selected practices were age, higher levels of education and income,
      never smoking, and strenuous physical activity. The survivors adopted healthier
      lifestyles, which were similar to those of women who never had cancer.
      CONCLUSIONS: About 10 years after BC diagnosis, the survivors generally comply
      with primary and secondary prevention practices.

PMID- 28432495
TI  - Investigating emotional contagion in dogs (Canis familiaris) to emotional sounds
      of humans and conspecifics.
AB  - Emotional contagion, a basic component of empathy defined as emotional state
      matching between individuals, has previously been shown in dogs even upon solely
      hearing negative emotional sounds of humans or conspecifics. The current
      investigation further sheds light on this phenomenon by directly contrasting
      emotional sounds of both species (humans and dogs) as well as opposed valences
      (positive and negative) to gain insights into intra- and interspecies empathy as
      well as differences between positively and negatively valenced sounds. Different
      types of sounds were played back to measure the influence of three dimensions on
      the dogs' behavioural response. We found that dogs behaved differently after
      hearing non-emotional sounds of their environment compared to emotional sounds of
      humans and conspecifics ("Emotionality" dimension), but the subjects responded
      similarly to human and conspecific sounds ("Species" dimension). However, dogs
      expressed more freezing behaviour after conspecific sounds, independent of the
      valence. Comparing positively with negatively valenced sounds of both species
      ("Valence" dimension), we found that, independent of the species from which the
      sound originated, dogs expressed more behavioural indicators for arousal and
      negatively valenced states after hearing negative emotional sounds. This response
      pattern indicates emotional state-matching or emotional contagion for negative
      sounds of humans and conspecifics. It furthermore indicates that dogs recognized
      the different valences of the emotional sounds, which is a promising finding for
      future studies on empathy for positive emotional states in dogs.

PMID- 28432497
TI  - Immobilization of Ulp1 protease on NHS-activated Sepharose: a useful tool for
      cleavage of the SUMO tag of recombinant proteins.
AB  - OBJECTIVE: To fabricate an active and stable enzyme through covalent
      immobilization, a Ubl-specific protease (Ulp1) was used to cleave small ubiquitin
      like modifier (SUMO) fusion proteins. RESULTS: We immobilized Ulp1 on N
      hydroxysuccinimide (NHS)-activated Sepharose with a coupling efficiency of 1.7
      mg/ml. The immobilized Ulp1 maintains 95% substrate-cleavage ability and
      significantly enhances pH and thermal stability, especially can withstand pH of
      10.5. Besides resistance against some small molecules, the immobilized Ulp1 can
      tolerate 15% (v/v) DMSO and 20% (v/v) ethanol. It can be reused for more than 15
      batch reactions with 90% activity retention. This provides a fast purification
      system to quickly obtain cleaved recombinant proteins with 95% purity from cell
      lysates with the application of immobilized Ulp1. CONCLUSIONS: Ulp1 used in
      immobilization form is a potentially useful tool for cleavage of SUMO-tagged
      proteins and may reduce time and cost of protein purification.

PMID- 28432496
TI  - Reproductive effects of life-cycle exposure to difenoconazole on female marine
      medaka (Oryzias melastigma).
AB  - Difenoconazole (DFZ) is a widely used triazole fungicide which has been detected
      in some estuaries and embayments. This study was conducted to investigate the
      effects of DFZ on ovarian development in female marine medaka (Oryzias
      melastigma). After 180 days exposure of the embryo to DFZ (0, 1, 10, 100 and 1000
      ng/L), the gonadosomatic index and percentage of mature oocytes produced were
      significantly reduced in the 1, 10 and 100 ng/L treatments but not the 1000 ng/L
      treatment compared to the control, thus exhibiting a U-shaped dose response
      curve. The relative mRNA levels of brain follicle-stimulating hormone, ovarian
      cytochrome P450 aromatase (CYP19s), hepatic estrogen receptors and vitellogenin,
      and the ratio of 17beta-estradiol to testosterone in the muscle, also showed a U
      shaped dose response, which was consistent with the development of oocytes. In
      addition, glutathione S-transferase activity in the ovary showed a U-shaped dose
      response. These results gave an explanation for this U-shaped dose-response. The
      egg number produced, the hatch ability and the swim-up success in the F1
      generation all showed a U-shaped dose response, indicating that exposure to DFZ
      at low concentrations can cause a decrease of fecundity and viability of the next
      generation. Thus, a more extensive evaluation of the impact of DFZ on marine fish
      reproduction at realistic environmental concentrations is needed.

PMID- 28432498
TI  - Co-cultivation of Chlamydomonas reinhardtii with Azotobacter chroococcum improved
      H2 production.
AB  - OBJECTIVES: To improve H2 production, the green algae Chlamydomonas reinhardtii
      cc849 was co-cultured with Azotobacter chroococcum. RESULTS: The maximum H2
      production of the co-culture was 350% greater than that of the pure algal
      cultures under optimal H2 production conditions. The maximum growth and the
      respiratory rate of the co-cultures were about 320 and 300% of the controls, and
      the dissolved O2 of co-cultures was decreased 74%. Furthermore, the in vitro
      maximum hydrogenase activity of the co-culture was 250% greater than that of the
      control, and the in vivo maximum hydrogenase activity of the co-culture was 1.4
      fold greater than that of the control. In addition, the maximum starch content of
      co-culture was 1400% that of the control. CONCLUSIONS: Azotobacter chroococcum
      improved the H2 production of the co-cultures by decreasing the O2 content and
      increasing the growth and starch content of the algae and the hydrogenase
      activity of the co-cultures relative to those of pure algal cultures.

PMID- 28432499
TI  - Depressive Symptoms and Tobacco Use: Does Religious Orientation Play a Protective
      Role?
AB  - Many studies have established an association between depression and smoking. The
      main objective of this study was to determine whether religious orientation
      moderates the relationship between depressive symptoms and tobacco use. This
      study utilized a cross-sectional data collection strategy to examine the
      relationship among depressive symptoms, religious orientation, and tobacco use
      among undergraduate students (N = 349) at a midsize southeastern university.
      Participants completed a demographic questionnaire, the Center for Epidemiologic
      Studies Depression Scale, the Extrinsic/Intrinsic Religious Orientation Scale
      Revised and the Drinking and Drug Habits Questionnaire. Analyses using
      hierarchical linear regression indicate a significant interaction effect
      (depressive symptoms * extrinsic religious orientation) on tobacco use.
      Additional moderation analyses reveal a significant interaction effect between
      depressive symptoms and the extrinsic-personal religious orientation on tobacco
      use. Results suggest that having an extrinsic religious orientation, and
      specifically, the extrinsic-personal subtype, can protect against the effects of
      depressive symptoms. In this regard, individuals who turn to religion for solace
      or comfort may be less likely to engage in tobacco use when experiencing
      depressive symptoms. Limitations, future directions, and implications are
      discussed.

PMID- 28432500
TI  - Walking over 4 Gya: Chemical Evolution from Photochemistry to Mineral and Organic
      Chemistries Leading to an RNA World.
AB  - Here we overview the chemical evolution of RNA molecules from inorganic material
      through mineral-mediated RNA formation compatible with the plausible early Earth
      environments. Pathways from the gas-phase reaction to the formation of
      nucleotides, activation and oligomerization of nucleotides, seem to be compatible
      with specific environments. However, how these steps interacted is not clear
      since the chemical conditions are frequently different and can be incompatible
      between them; thus the products would have migrated from one place to another,
      suitable for further chemical evolution. In this review, we summarize certain
      points to scrutinize the RNA World hypothesis.

PMID- 28432502
TI  - Erratum to: Sex Differences and Predictors of Changes in Body Weight and
      Noncommunicable Diseases in a Random, Newly-Arrived Group of Refugees Followed
      for Two Years.

PMID- 28432501
TI  - High-scale yield of nano hydroxyapatite through combination of mechanical
      activation and chemical dispersion.
AB  - The aim of this study is to develop a simple, convenient and effective approach
      to synthesize nano-sized hydroxyapatite (nano-HA) at high-scale yield. Nano-HA
      was wet synthesized in the presence or absence of alendronate sodium (ALN), one
      of bisphosphonates for anti-osteoporotic. Then aged and washed nano-HA
      precipitate was directly treated by mechanical activation combined with the
      chemical dispersion of ALN to prevent the agglomeration of nano-HA. ALN acted not
      only as a chemical dispersant but also as an orthopedic drug. In vitro release
      showed that ALN was released slowly from nano-HA. Transmission electron
      microscopy (TEM) revealed that nano-HA with size less than 100 nm appeared as
      single particle after being treated by mechanical activation combined with the
      dispersion of ALN (AMA-HA and MA-HA). High resolution transmission electron
      microscopy (HRTEM) and X-ray diffraction (XRD) confirmed that as-prepared
      nanoparticles were HA with low crystallinity and crystallite size. Fourier
      transform infrared spectroscopy (FTIR) indicated that the phosphonate groups in
      ALN were introduced to bond with the Ca2+ of HA to impede the growth of HA
      crystal. Zeta potential illustrated that the absolute value of surface negative
      charge of nano-HA increased significantly with the addition of ALN, which
      inhibited the agglomeration of nano-HA. The present approach makes it feasible to
      produce nano-HA at high-scale yield, which provide the possibility to construct
      bone graft.

PMID- 28432503
TI  - High-voltage zones within the pulmonary vein antra: Major determinants of acute
      pulmonary vein reconnections after atrial fibrillation ablation.
AB  - PURPOSE: Recurrence of atrial fibrillation (AF) after pulmonary vein isolation
      (PVI) is mainly due to PV reconnections. Patient-specific tissue characteristics
      that may contribute remain unidentified. This study aimed to assess the
      relationship between the bipolar electrogram voltage amplitudes recorded from the
      PV-left atrial (LA) junction and acute PV reconnection sites. METHODS: Three
      dimensional LA voltage maps created before an extensive encircling PVI in 47 AF
      patients (31 men; mean age 62 +/- 11 years) were examined for an association
      between the EGM voltage amplitude recorded from the PV-LA junction and acute post
      PVI PV reconnections (spontaneous PV reconnections and/or ATP-provoked dormant PV
      conduction). RESULTS: Acute PV reconnections were observed in 17 patients (36%)
      and in 24 (3%) of the 748 PV segments (16 segments per patient) and were
      associated with relatively high bipolar voltage amplitudes (3.26 +/- 0.85 vs.
      1.79 +/- 1.15 mV, p < 0.0001) and a relatively low mean force-time integral (FTI)
      (428 +/- 56 vs. 473 +/- 76 gs, p = 0.0039) as well as FTI/PV-LA bipolar voltage
      (137 [106, 166] vs. 295 [193, 498] gs/mV, p < 0.0001). An analysis of the
      receiver operating characteristic curves revealed a high prognostic performance
      of the LA bipolar voltage and FTI/PV-LA bipolar voltage for acute PV
      reconnections (areas under the curve: 0.86 and 0.89, respectively); the best
      cutoff values were >2.12 mV and <=183 gs/mV, respectively. CONCLUSIONS: The PV-LA
      voltage on the PV-encircling ablation line and FTI/PV-LA voltage were related to
      the acute post-PVI PV reconnections. A more durable ablation strategy is
      warranted for high-voltage zones.

PMID- 28432504
TI  - 3T MRI of the knee with optimised isotropic 3D sequences: Accurate delineation of
      intra-articular pathology without prolonged acquisition times.
AB  - OBJECTIVES: To investigate optimised isotropic 3D turbo spin echo (TSE) and
      gradient echo (GRE)-based pulse sequences for visualisation of articular
      cartilage lesions within the knee joint. METHODS: Optimisation of experimental
      imaging sequences was completed using healthy volunteers (n=16) with a 3-Tesla
      (3T) MRI scanner. Imaging of patients with knee cartilage abnormalities (n=57)
      was then performed. Acquired sequences included 3D proton density-weighted (PDW)
      TSE (SPACE) with and without fat-suppression (FS), and T2*W GRE (TrueFISP)
      sequences, with acquisition times of 6:51, 6:32 and 5:35 min, respectively.
      RESULTS: One hundred sixty-one confirmed cartilage lesions were detected and
      categorised (Grade II n=90, Grade III n=71). The highest sensitivity and
      specificity for detecting cartilage lesions were obtained with TrueFISP with
      values of 84.7% and 92%, respectively. Cartilage SNR mean for PDW SPACE-FS was
      the highest at 72.2. TrueFISP attained the highest CNR means for joint
      fluid/cartilage (101.5) and joint fluid/ligament (156.5), and the lowest CNR for
      cartilage/meniscus (48.5). Significant differences were identified across the
      three sequences for all anatomical structures with respect to SNR and CNR
      findings (p-value <0.05). CONCLUSION: Isotropic TrueFISP at 3T, optimised for
      acquisition time, accurately detects cartilage defects, although it demonstrated
      the lowest contrast between cartilage and meniscus. KEY POINTS: * Cartilage is
      better visualised with 3D TrueFISP than 3D SPACE sequences. * 3D TrueFISP is a
      reliable sequence for detecting low- and high-grade cartilage defects. * 3D
      TrueFISP at 3T provides excellent contrast between cartilage and joint fluid.

PMID- 28432505
TI  - 3D double-echo steady-state sequence assessment of hip joint cartilage and labrum
      at 3 Tesla: comparative analysis of magnetic resonance imaging and intraoperative
      data.
AB  - OBJECTIVES: To assess the diagnostic accuracy of a high-resolution, three
      dimensional (3D) double-echo steady-state (DESS) sequence with radial imaging at
      3 Tesla (T) for evaluating cartilage and labral alterations in the hip. METHODS:
      Magnetic resonance imaging (MRI) data obtained at 3 T, including radially
      reformatted DESS images and intraoperative data of 45 patients (mean age 42 +/-
      13.7 years) who underwent hip arthroscopy, were compared. The acetabular
      cartilage and labrum of the upper hemisphere of the acetabulum and the central
      femoral head cartilage were evaluated. Sensitivity, specificity, accuracy, and
      negative and positive predictive values were determined. RESULTS: Sensitivity,
      specificity and accuracy of the DESS technique were 96.7%, 75% and 93.7% for
      detecting cartilage lesions and 98%, 76.2% and 95.9% for detecting labral
      lesions. The positive and negative predictive values for detecting or ruling out
      cartilage lesions were 96% and 78.9%. For labral lesions, the positive and
      negative predictive values were 97.5% and 80%. CONCLUSION: A high-resolution, 3D
      DESS technique with radial imaging at 3 T demonstrated high accuracy for
      detecting hip cartilage and labral lesions with excellent interobserver agreement
      and moderate correlation between MRI and intraoperative assessment. KEY POINTS: *
      High-resolution, 3D DESS with radial imaging allows accurate cartilage and labrum
      evaluation. * DESS demonstrated high sensitivity, specificity, accuracy for
      detecting cartilage and labral lesions. * Highly accurate sequence may influence
      treatment decisions in patients with hip pain.

PMID- 28432506
TI  - Elective Colectomy for Diverticulitis in Transplant Patients: Is It Worth the
      Risk?
AB  - BACKGROUND: The aim of this study was to determine morbidity and mortality for
      transplant patients undergoing elective colectomy for diverticulitis and
      determine the impact of recurrent diverticulitis on postoperative complications.
      METHODS: We identified transplant recipients that underwent elective colectomy
      for diverticulitis between 2000 and 2015 at a tertiary care institution. Patient
      and procedure variables, postoperative complications, length of stay, 30-day
      readmission, and mortality were identified through retrospective chart review.
      Complication rates were compared between patients with one previous episode of
      diverticulitis versus two or more. RESULTS: Thirty transplant recipients
      underwent colectomy for primary (n = 13) or recurrent (n = 17) diverticulitis.
      Primary anastomosis was performed in 26 (87%) with proximal diversion in 10
      (38%). The overall complication rate was 57%, with surgical site infection being
      the most common (23%). There were no anastomotic leaks at the colorectal
      anastomosis or reoperations. Median length of stay was 8 days (range 4-23).
      Postoperative complications were not significantly different between groups (54
      vs. 59%, p = 0.94). CONCLUSIONS: Postoperative morbidity after elective colectomy
      for diverticulitis in transplant recipients was common. There were no differences
      in complications for patients with primary versus recurrent diverticulitis. Fear
      of postoperative complications from recurrent diverticulitis should not be a
      reason to recommend elective colectomy after an initial attack of diverticulitis
      in transplant patients.

PMID- 28432508
TI  - Estimation of environmental flow incorporating water quality and hypothetical
      climate change scenarios.
AB  - Environmental flows (Eflow, hereafter) are the flows to be maintained in the
      river for its healthy functioning and the sustenance and protection of aquatic
      ecosystems. Estimation of Eflow in any river stretch demands consideration of
      various factors such as flow regime, ecosystem, and health of river. However,
      most of the Eflow estimation studies have neglected the water quality factor.
      This study urges the need to consider water quality criterion in the estimation
      of Eflow and proposes a framework for estimating Eflow incorporating water
      quality variations under present and hypothetical future scenarios of climate
      change and pollution load. The proposed framework is applied on the polluted
      stretch of Yamuna River passing through Delhi, India. Required Eflow at various
      locations along the stretch are determined by considering possible variations in
      future water quantity and quality. Eflow values satisfying minimum quality
      requirements for different river water usage classes (classes A, B, C, and D as
      specified by the Central Pollution Control Board, India) are found to be between
      700 and 800 m3/s. The estimated Eflow values may aid policymakers to derive
      upstream storage-release policies or effluent restrictions. Generalized nature of
      this framework will help its implementation on any river systems.

PMID- 28432507
TI  - Study of the potential of barnyard grass for the remediation of Cd- and Pb
      contaminated soil.
AB  - In this study, the microwave digestion method was used to determine total cadmium
      (Cd) and lead (Pb) concentrations, the BCR method was used to determine different
      states of Cd and Pb, and atomic absorption spectroscopy (AAS) and inductively
      coupled plasma optical emission spectrometry (ICP-OES) were used to determine Cd
      and Pb concentrations in simulated soil and barnyard grass before and after
      planting barnyard grass to provide a theoretical basis for the remediation of Cd-
      and Pb-contaminated soil. The results showed that the bioconcentration factor
      changes with different Cd concentrations are relatively complex and that the
      removal rate increases regularly. The 100 mg kg-1 Cd treatment had the highest
      removal rate, which reached 36.66%. For Pb, the bioconcentration factor decreased
      and tended to reach equilibrium as the Pb concentration increased. The highest
      removal rate was 41.72% and occurred in the 500 mg kg-1 Pb treatment; however,
      this removal rate was generally lower than that of Cd. In addition, the reduction
      state had the highest change rate, followed by the residual, acid soluble and
      oxidation states. For Pb, the residual state has the highest change rate,
      followed by the acid soluble state, reduction state and oxidation state. In
      addition, a significant correlation was observed between the soil Pb and Cd
      concentrations and the concentrations of Pb and Cd that accumulated in the
      belowground biomass of the barnyard grass, but no significant correlation was
      observed between the soil Pb and Cd concentrations and the amounts of Pb and Cd
      that accumulated in the aboveground biomass of the barnyard grass. The highest
      transfer factor of Cd was 0.49, which occurred in the 5 mg kg-1 Cd treatment. The
      higher transfer factor of Pb was 0.48 in the 100 mg kg-1 Pb treatment. All of
      these factors indicate that the belowground biomass of barnyard grass plays a
      more important role in the remediation of Cd- and Pb-contaminated soils than the
      aboveground biomass of barnyard grass. Remediation should occur through
      phytostabilization. Thus, with its strong adaptability and lush growth, barnyard
      grass can be applied as a pioneer species for the phytoremediation of Cd- and Pb
      contaminated soils.

PMID- 28432509
TI  - Assessment of cadmium content of potato grown in Weining County, Guizhou
      Province, China.
AB  - A total of 54 soil and 54 potato samples have been collected from Weining County
      to evaluate the accumulation of cadmium in potatoes. The concentrations of the
      total Cd and the available Cd in the soil samples have been detected. The total
      concentrations of Cd were from 0.41 to 10.0 mg/kg with an average value of 2.60
      mg/kg in soil. The concentrations of available Cd in the soil were 0.07 to 3.47
      mg/kg with an average value of 0.59 mg/kg. The concentration of the available Cd
      showed a good linear positive correlation with the total Cd content in the soil.
      For the 54 potato samples, the Cd concentrations were from 0.023 to 0.18 mg/kg
      with an average value 0.083 mg/kg (fresh weight).The bioconcentration factor
      (BCF) values of Cd in potatoes, based on dry weight, were from 0.02 to 0.96 with
      an average value 0.24. The uptake of cadmium by plants is dependent on various
      soil and environmental factors. A regression model to predict the concentration
      of cadmium in Weining potatoes based on soil properties and elevation was
      developed. The results showed the elevation and the soil pH played an important
      role and had a negative influence on the uptake of Cd by potato in Weining
      County. The mean intake of Cd by adults through consumption of potato from
      Weining would be 5.9 MUg/day, and it is well below the provisionally tolerable
      daily intake for Cd (70 MUg/day).

PMID- 28432510
TI  - Epilithic diatom assemblages and their relationships with environmental variables
      in the Nilufer Stream Basin, Bursa, Turkey.
AB  - Patterns of epilithic diatom species distribution in relation to environmental
      variables from 12 sampling sites on the main stream and some of its tributaries
      in the Nilufer Stream Basin were determined using multivariate statistical
      techniques. The stream basin has been heavily influenced by anthropogenic
      effects. The upper part of the basin that is distant from pollution sources
      mostly has a spring water quality, while the lower part where the stream flows
      through the urban area and receives domestic and industrial wastewater has a
      quite low quality. Ordination techniques using both diatom taxa and 21
      environmental variables revealed non- to slightly polluted upper basin sites and
      highly polluted lower basin sites along the stream. The results showed that the
      stream catchment is polluted gradually from upstream to downstream and that most
      of the downstream sites have very low water quality especially in summer months.
      A total of 134 epilithic diatom taxa belonging to 50 genera were recorded for 12
      sample sites. Partial CCA results indicated that water temperature (T), discharge
      (Q), and total phosphorus (TP) were the most important variables affecting the
      distribution of diatom species. Unpolluted or slightly polluted upper basin sites
      were dominated by Achnanthidium minutissimum, Cocconeis placentula var. euglypta,
      Gomphonema olivaceum, and Navicula tripunctata. Highly polluted lower basin sites
      were characterized by high levels of organic and inorganic matters and low
      dissolved oxygen (DO) values. Species widespread in the highly polluted lower
      basin sites such as Nitzschia umbonata, Nitzschia amphibia, Nitzschia
      capitellata, Nitzschia palea, Nitzschia paleacea, Luticola mutica, and
      Stephanodiscus niagarae were mostly related to pollution indicator variables such
      as ammonium nitrogen (NH4+-N), sodium (Na+), total phosphorus (TP), and total
      organic matter (TOM).

PMID- 28432511
TI  - Environmental management zoning for coal mining in mainland China based on
      ecological and resources conditions.
AB  - The purpose of this research is to establish an environmental management zoning
      for coal mining industry which is served as a basis for making environmental
      management policies. Based on the specific impacts of coal mining and regional
      characteristics of environment and resources, the ecological impact, water
      resources impact, and arable land impact are chose as the zoning indexes to
      construct the index system. The ecological sensitivity is graded into three
      levels of low, medium, and high according to analytical hierarchy processes and
      gray fixed weight clustering analysis, and the water resources sensitivity is
      divided into five levels of lower, low, medium, high, and higher according to the
      weighted sum of sub-indexes, while only the arable land sensitive zone was
      extracted on the basis of the ratio of arable land to the county or city. By
      combining the ecological sensitivity zoning and the water resources sensitive
      zoning and then overlapping the arable-sensitive areas, the mainland China is
      classified into six types of environmental management zones for coal mining
      except to the forbidden exploitation areas.

PMID- 28432512
TI  - Squamous cell carcinoma of the breast in the United States: incidence,
      demographics, tumor characteristics, and survival.
AB  - PURPOSE: Squamous cell carcinoma of breast accounts for less than 0.1% of all
      breast cancers. The purpose of this study is to describe the epidemiology and
      survival of this rare malignancy. METHODS: Data were extracted from the National
      Cancer Institute's Surveillance, Epidemiology and End Results Registry to
      identify women diagnosed with squamous cell carcinoma of breast between 1998 and
      2013. SEER*Stat 8.3.1 was used to calculate age-adjusted incidence, age-wise
      distribution, and annual percentage change in incidence. Kaplan-Meier curves were
      plotted for survival analysis. Univariate and multivariate Cox proportional
      hazard regression model was used to determine predictors of survival. RESULTS: A
      total of 445 cases of squamous cell carcinoma of breast were diagnosed during the
      study period. The median age of diagnosis was 67 years. The overall age-adjusted
      incidence between 1998 and 2013 was 0.62 per 1,000,000 per year, and the
      incidence has been on a decline. Approximately half of the tumors were poorly
      differentiated. Stage II was the most common stage at presentation. Majority of
      the cases were negative for expression of estrogen and progesterone receptor. One
      third of the cases underwent breast conservation surgery while more than half of
      the cases underwent mastectomy (unilateral or bilateral). Approximately one-third
      of cases received radiation treatment. The 1-year and 5-year cause-specific
      survival was 81.6 and 63.5%, respectively. Excluding patient with metastasis or
      unknown stage at presentation, in multivariate Cox proportional hazard model,
      older age at diagnosis and higher tumor stage (T3 or T4) or nodal stage at
      presentation were significant predictors of poor survival. CONCLUSIONS: Our study
      describes the unique characteristics of squamous cell carcinoma of breast and
      demonstrates that it is an aggressive tumor with a poor survival. Older age and
      higher tumor or nodal stages at presentation were independent predictors of poor
      survival for loco-regional stages.

PMID- 28432513
TI  - The relationship between statins and breast cancer prognosis varies by statin
      type and exposure time: a meta-analysis.
AB  - PURPOSE: Breast cancer is the most common cancer in females and the leading cause
      of death worldwide. The effects of statins on breast cancer prognosis have long
      been controversial; thus, it is important to investigate the relationship between
      statin type, exposure time, and breast cancer prognosis. This study sought to
      explore the effect of statins, as well as the different effects of statin
      solubility and variable follow-up times, on breast cancer prognosis. METHODS: We
      searched the MEDLINE (via PubMed), EMBASE (via OvidSP), Cochrane Library, and ISI
      Web of Knowledge databases using combinations of the terms "breast
      neoplasms[MeSH]," "statins" or "lipid-lowering drug," "prognosis" or "survival,"
      or "mortality" or "outcome" with no limit on the publication date. We searched
      the databases between inception and October 15, 2016. Reference lists of the
      included studies and relevant reviews were also manually screened. The initial
      search identified 71 publications, and 7 of these studies, which included a total
      of 197,048 women, met the selection criteria. Two authors independently screened
      each study for inclusion and extracted the data. The data were analyzed using
      Stata/SE 11.0. RESULTS: Overall statin use was associated with lower cancer
      specific mortality and all-cause mortality, although the benefit appeared to be
      constrained by statin type and follow-up time. Lipophilic statins were associated
      with decreased breast cancer-specific and all-cause mortality; however,
      hydrophilic statins were weakly protective against only all-cause mortality and
      not breast cancer-specific mortality. Of note, one group with more than 4 years
      of follow-up did not show a significant correlation between statin use and cancer
      specific mortality or all-cause mortality, whereas groups with less than 4 years
      of follow-up still showed the protective effect of statins against cancer
      specific mortality and all-cause mortality. CONCLUSIONS: Although statins can
      reduce breast cancer patient mortality, the benefit appears to be constrained by
      statin type and follow-up time. Lipophilic statins showed a strong protective
      function in breast cancer patients, whereas hydrophilic statins only slightly
      improved all-cause mortality. Finally, the protective effect of statins could
      only be observed in groups with less than 4 years of follow-up. These findings
      are meaningful in clinical practice, although some conclusions contradict
      conventional wisdom and will thus require further exploration.

PMID- 28432514
TI  - Breast cancer treatment costs in younger, privately insured women.
AB  - PURPOSE: Younger women (under age 45 years) diagnosed with breast cancer often
      face more aggressive tumors, higher treatment intensity, lower survival rates,
      and greater financial hardship. The purpose of this study was to estimate breast
      cancer costs by stage at diagnosis during the first 18 months of treatment for
      privately insured younger women. METHODS: We analyzed North Carolina cancer
      registry data linked to claims data from private insurers from 2003 to 2010.
      Breast cancer patients were split into two cohorts: a younger and older group
      aged 21-44 and 45-64 years, respectively. We conducted a cohort study and matched
      women with and without breast cancer using age, ZIP, and Charlson Comorbidity
      Index. We calculated mean excess costs between breast cancer and non-breast
      cancer patients at 6, 12, and 18 months. RESULTS: For younger women, AJCC 6th
      edition stage II cancer was the most common at diagnosis (40%), followed by stage
      I (34%). On the other hand, older women had more stage I (46%) cancer followed by
      stage II (34%). The excess costs for younger and older women at 12 months were
      $97,486 (95% confidence interval [CI] $93,631-101,341) and $75,737 (95% CI
      $73,962-77,512), respectively. Younger breast cancer patients had both a higher
      prevalence of later-stage disease and higher within-stage costs. CONCLUSIONS: The
      study reports high costs of treatment for both younger and older women than a non
      cancer comparison group; however, the estimated excess cost was significantly
      higher for younger women. The financial implications of breast cancer treatment
      costs for younger women need to be explored in future studies.

PMID- 28432515
TI  - MRI predicts pathologic complete response in HER2-positive breast cancer after
      neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant treatment of HER2-positive breast cancer frequently leads
      to a pathologic complete response (pCR), which is associated with favourable long
      term outcome. Treatment regimens typically consist of 6-9 cycles of trastuzumab
      based chemotherapy, although many patients achieve early radiologic complete
      response (rCR). If rCR accurately predicts pCR, the number of chemotherapy cycles
      can possibly be reduced. METHODS: We performed a diagnostic accuracy study to
      determine the association between rCR and pCR in patients with stage II-III HER2
      positive breast cancer treated with neoadjuvant trastuzumab-based chemotherapy at
      the Netherlands Cancer Institute. RCR was defined as the disappearance of
      pathologic contrast enhancement in the original tumour region on repeated
      magnetic resonance imaging (MRI). PCR was defined as the absence of invasive
      tumour cells in the resected breast specimen (ypT0/is). Diagnostic accuracy was
      estimated in the overall population and in subgroups based on hormone receptor
      (HR) status. The prognostic value of rCR for recurrence-free interval was
      evaluated as an exploratory analysis. RESULTS: We identified 296 eligible
      patients with 297 HER2-positive tumours (154 HR-negative and 143 HR-positive)
      treated with neoadjuvant trastuzumab-based chemotherapy between 2004 and 2016.
      Overall, the rCR rate was 69% (206/297) and the pCR rate was 61% (181/297). Among
      206 patients with rCR, 150 also had pCR (negative predictive value [NPV] =
      150/206 = 73%). Among 91 patients without rCR, 60 had residual tumour at
      pathology (positive predictive value [PPV] = 60/91 = 66%). The NPV was better in
      HR-negative compared to HR-positive tumours (88 vs. 57%), while the PPV was
      better in HR-positive tumours (50 vs. 78%). Achieving rCR was associated with a 5
      year recurrence-free interval of 88% compared to 68% without rCR (hazard ratio
      0.34, 95% confidence interval 0.17-0.65, P = 0.001). CONCLUSION: Achieving rCR
      corresponds well with pCR in HER2-positive breast cancer, particularly in the HR
      negative subgroup. RCR is also associated with improved long-term outcome.

PMID- 28432516
TI  - The Tower of London (ToL) in Italy: standardization of the ToL test in an Italian
      population.
AB  - Deficit in planning and problem-solving, affecting a wide range of
      neuropsychological patients, has been widely investigated using the Tower of
      London (ToL) test, as developed by Shallice (Philos Trans R Soc Lond Ser B Biol
      Sci 298:199-209, 1). The ToL taps on several executive functions (EF), such as
      planning, time for planning or rule breaks, which may be usefully indexed by
      different ToL measurements. However, in its original version, the different
      aspects involved in ToL are not evaluated in a specific way.Here, we report the
      standardization of the ToL, on 896 individuals aged 15-86 years, taking in
      account individual factors (i.e. gender, age, years of education) which may
      affect performances on ToL. We computed several indexes on the ToL including
      score, planning and execution times, perseverations, rule breaks and self
      monitoring. We found that these indexes were affected by individual factors such
      as gender, age and education. Present results not only provide extensive
      normative data according to gender, as well as different age and education
      ranges, but also represent a very useful instrument for a more fine-grained
      diagnosis of EF deficits in a wide range of neuropsychological patients,
      including traumatic brain injury and brain-damaged patients, as well as
      Alzheimer's disease and Parkinson's disease patients.

PMID- 28432517
TI  - Cerebral large-vessel vasculitis as an unusual manifestation of POEMS syndrome.

PMID- 28432518
TI  - Correlation between heavy metal exposure and GSTM1 polymorphism in Iranian
      multiple sclerosis patients.
AB  - Multiple sclerosis (MS) is an immune-mediated chronic inflammatory disease of the
      central nervous system. Various exposures to heavy metals can lead to toxicity
      and oxidative stress. While glutathione-S-transferases are known as oxidative
      stress-related genes and involved in metal biotransformation. The aim of the
      present study is to investigate the correlation of GSTM1 polymorphism in MS
      patients and the possible association with blood concentration of arsenic (As)
      and cadmium (Cd) as major heavy metal pollutants. This study included 69
      relapsing-remitting multiple sclerosis patients and 74 age/gender-matched healthy
      subjects. The genetic profile was analyzed by PCR, and heavy metal concentrations
      were measured by electrothermal atomic absorption spectrometry. Our results
      demonstrated that patients with the GSTM1 null genotype had considerably lower
      age of onset. However, the frequency of the GSTM1 null genotype was not
      significantly different between MS and control groups. In addition, the blood As
      and Cd concentrations were considerably higher in MS patients in comparison with
      healthy individuals. Also, it revealed that the GSTM1 null genotype associated
      with high Cd level in MS patients. There was also a trend toward an increase in
      As level in MS patients. These data may point to susceptibility to cadmium
      toxicity especially in RR-MS patients with smoking habit. Furthermore, the M1
      null genotype will help in a prognosis of MS considering the age of onset. It
      confirms that the long-term prognosis in MS and patient's disability are
      influenced by their ability to remove the toxic products and perhaps to decrease
      oxidative stress.

PMID- 28432519
TI  - Carotid plaque with expansive arterial remodeling is a risk factor for ischemic
      complication following carotid artery stenting.
AB  - BACKGROUND: Carotid artery stenting (CAS) is associated with a higher risk of
      periprocedural stroke than carotid endarterectomy. For better patient selection,
      more accurate risk factors should be identified. The aim of this study was to
      determine whether expansive arterial remodeling can predict ischemic
      complications in patients undergoing CAS. METHODS: This retrospective study
      included 82 patients with carotid stenosis treated by CAS. The plaque component
      was evaluated using MR plaque imaging before the procedure. Following the
      procedure, lesion assessment was performed using MRI diffusion-weighted imaging
      (DWI), and patients were classified as DWI positive or negative for comparison
      between groups. RESULTS: Fifteen patients were classified as DWI positive and 67
      patients as DWI negative. The mean expansive remodeling rate was 1.76 +/- 0.21 in
      the DWI-positive group and 1.35 +/- 0.18 in the DWI-negative group (P < 0.001).
      Receiver-operating characteristic analysis revealed that the threshold for the
      expansive remodeling rate separating the two groups was 1.52 (area under the
      curve = 0.933). The positive predictive value of postoperative new DWI lesions in
      the high-intensity plaque associated with a high expansive remodeling rate was
      64.3%, and the negative predictive value of the isointensity plaque associated
      with a low expansive remodeling rate was 97.8%. These values were higher than
      those of the plaque component alone (32.1% and 81.7%, respectively). CONCLUSIONS:
      This study revealed that expansive arterial remodeling is a strong risk predictor
      of ischemic complication in CAS. Expansive remodeling rate measurements are very
      simple and provide useful information for determining treatment strategies for
      patients with carotid stenosis.

PMID- 28432520
TI  - Unexpected death after occipital condylar fracture.
AB  - We present a rare fatal complication of an occipital condylar fracture. The
      patient was initially neurologically intact, but showed secondary clinical
      deterioration. Imaging revealed extensive extra-axial hemorrhage at the
      craniocervical junction and an acute obstructive hydrocephalus. MR imaging
      demonstrated a T2 hyperintens signal in both the lower brainstem and upper
      cervical spinal cord, likely caused by the extra-axial hemorrhage. As prognosis
      was estimated infaust, supportive treatment was discontinued and the patient died
      soon thereafter. This case report illustrates a rare, delayed complication and
      unexpected death in a patient having sustained an occipital condylar fracture.

PMID- 28432521
TI  - Intermittent food restriction initiated late in life prolongs lifespan and
      retards the onset of age-related markers in the annual fish Nothobranchius
      guentheri.
AB  - Two of the most studied and widely accepted conjectures on possible aging
      mechanisms are the oxidative stress hypothesis and the insulin/insulin-like
      growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is
      known to modulate aging and to prolong lifespan in a variety of organisms, but
      the mechanisms are still under debate. In this study, we first demonstrated that
      late-onset two consecutive days a week fasting, a form of IF, termed intermittent
      food restriction (IFR), exhibited a time-dependent effect, and long-term late
      onset IFR extended the mean lifespan and maximum lifespan by approximately 3.5
      and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We also
      showed that IFR reduced the accumulation of lipofuscin in the gills and the
      protein oxidation and lipid peroxidation levels in the muscles. Moreover, IFR was
      able to enhance the activities of antioxidant enzymes catalase, glutathione
      peroxidase, and superoxide dismutase in the fish. Finally, IFR was also able to
      decelerate the decrease of SirT1 and Foxo3A, but accelerate the decrease of IGF
      1. Collectively, our findings suggest that late-onset IFR can retard the onset of
      age-related markers, and prolong the lifespan of the aging fish, via a
      synergistic action of an anti-oxidant system and the IIS pathway. It also
      proposes that the combined assessment of anti-oxidant system and IIS pathway will
      contribute to providing a more comprehensive view of anti-aging process.

PMID- 28432522
TI  - Diagnostic uncertainty and epistemologic humility.

PMID- 28432523
TI  - Hypothesis-free analyses from a large psoriatic arthritis cohort support merger
      to consolidated peripheral arthritis definition without subtyping.
AB  - Current ClASsification criteria for Psoriatic ARthritis classification criteria
      for psoriatic arthritis (PsA) provide a preliminary definition of inflammatory
      articular disease. This study aimed to further characterize PsA peripheral
      arthritis using purely data-driven approaches for the affected joint distribution
      pattern. PsA patients from the Swiss Clinical Quality Management in Rheumatic
      Diseases (SCQM) database were clustered according to similarities in 66 swollen
      and in 68 tender joints. Clusters were compared in terms of other disease
      characteristics and studied for coincidence with traditional PsA subtypes,
      stability over time and treatment response upon first tumour necrosis factor
      alpha (TNF-alpha) therapy. Clustering of 957 patients resulted in an
      oligoarticular, a polyarticular hand dominated, a polyarticular foot dominated
      and a fourth cluster which was characterized by polyarticular involvement of the
      hands and feet. Of the traditional PsA subtypes, only a non-PsA-specific
      oligoarticular joint involvement pattern was retrieved by clustering. When
      comparing clusters in other disease manifestations, only minor and clinically
      probably irrelevant differences occurred. Over time, clusters were more robust
      than traditional PsA subtypes. Patients in different joint clusters had similar
      response rates upon first anti-TNF-alpha therapy, and minimal disease activity
      was achieved in 56% of 285 patients, irrespective of cluster membership.
      Hypothesis-free approaches to group PsA patients yield clusters with improved
      consistency, but without clinically important differences. Taken together, the
      current peripheral arthritis definition by GRAPPA without further specification
      into subtypes is strongly supported by the data.

PMID- 28432525
TI  - CORR Insights(r): Which Clinical and Patient Factors Influence the National
      Economic Burden of Hospital Readmissions After Total Joint Arthroplasty.

PMID- 28432526
TI  - Erratum to: How Trace Element Levels of Public Drinking Water Affect Body
      Composition in Turkey.

PMID- 28432524
TI  - Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients
      with ankylosing spondylitis: a pilot study.
AB  - The studies aimed to assess a set of biomarkers for their correlations with
      disease activity/severity of patients with ankylosing spondylitis (AS). A total
      of 24 AS patients were treated with etanercept and prospectively followed for 12
      weeks. Serum levels of TNF-alpha, IFN-gamma, TGF-beta, IL6, IL15, IL17, MMP3, and
      MICA were measured at baseline and after treatment. The change of these
      biomarkers was analyzed for correlations with MRI indices for joint inflammation,
      Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis
      Functional Index, AS Disease Activity Score, serum CRP, and ESR. The Wilcoxon
      rank sum test was used to compare the biomarker levels between pre- and post
      treatment and between pre-treatment and controls. Both step-wise procedures based
      on the Akaike information criterion (AIC) and least absolute shrinkage and
      selection operator with fivefold cross-validation were used to select the best
      model for pairwise correlations between the above clinical measures and the serum
      biomarkers. Serum levels of both MMP3 and IL6 were significantly higher in AS
      patients at baseline. After treatment, the levels of MMP3 decreased, but TGF-beta
      and TNF-alpha increased significantly . The changes of serum MMP3 and MICA were
      significantly associated with MRI sacroiliac joint (SIJ) scores. CRP was
      positively correlated with serum MMP3 and IL6. The pattern of combined changes of
      serum MICA, MMP3, TGF-beta, IL17, TNF-alpha, and IFN-gamma predicted the MRI
      score of SIJ by logistic regression analysis. Specific serum biomarkers were
      significantly associated with clinical measures of AS. Most prominently, serum
      MMP3 level was found to have a positive correlation with the MRI score of SIJ and
      CRP. Serum MICA level negatively correlated with disease remission.

PMID- 28432527
TI  - Effects of Agaricus blazei Murill Polysaccharide on Cadmium Poisoning on the MDA5
      Signaling Pathway and Antioxidant Function of Chicken Peripheral Blood
      Lymphocytes.
AB  - This experimental study investigated the effect of Agaricus blazei Murill
      polysaccharide (ABP) on cadmium (Cd) poisoning on the melanoma differentiation
      associated gene 5 (MDA5) signaling pathway and antioxidant function of peripheral
      blood lymphocytes (PBLs) in chickens. The experiments were divided into four
      groups: 7-day-old chickens with normal saline (0.2 mL single/day), Cd (140
      mg/kg), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP(140 mg/kg/day + 0.2 mL
      ABP). Peripheral blood was collected on the 20th, 40th, and 60th days for each
      group, and PBLs were separated. We attempted to detect the expression of MDA5,
      downstream signaling molecules, and convergence protein (interferon promoter
      stimulating factor 1); transcription factors (IRF3 and NF-kappaB); the content of
      cytokines (IL-1beta, IL-6, TNF-alpha, and IFN-beta) in PBLs; and the antioxidant
      index of superoxide dismutase (SOD), malondialdhyde (MDA), and glutathione
      peroxidase (GSH-Px). The results showed that ABP can reduce the accumulation of
      Cd in the peripheral blood of chickens; reduce the expression of MDA5 and
      downstream signaling molecules; and reduce the content of IL-1beta, IL-6, TNF
      alpha, and IFN-beta in PBLs of chickens. The activity of antioxidant enzymes (SOD
      and GSH-Px) significantly increased, and the content of MDA decreased. These
      results showed that they have a certain protective effect of ABP on Cd poisoning
      in chicken PBLs caused by injury.

PMID- 28432528
TI  - Conventional Acupuncture for Cardiac Arrhythmia: A Systematic Review of
      Randomized Controlled Trials.
AB  - OBJECTIVE: To exam the effect and safety of conventional acupuncture (CA) on
      cardiac arrhythmia. METHODS: Nine medical databases were searched until February
      2016 for randomized controlled trials. Heterogeneity was measured by Cochran Q
      test. Meta-analysis was conducted if I2 was less than 85% and the characteristics
      of included trials were similar. RESULTS: Nine qualified studies involving 638
      patients were included. Only 1 study had definitely low risk of bias, while 7
      trials were rated as unclear and 1 as high. Meta-analysis of CA alone did not
      have a significant benefit on response rate compared to amiodarone in patients
      with atrial fibrillation (Af) and atrial flutter (AF) [relative risk (RR): 1.09;
      95% confidence interval (CI): 0.79-1.49; P=0.61; I2=61%, P=0.11]. However, 1
      study with higher methodological quality detected a lower recurrence rate of Af
      in CA alone as compared with sham acupuncture plus no treatment, and benefits on
      ventricular rate and time of conversion to normal sinus rhythm were found in CA
      alone group by 1 study, as well as the response rate in CA plus deslanoside group
      by another study. Meta-analysis of CA plus anti-arrhythmia drug (AAD) was
      associated with a significant benefit on the response rate when compared with AAD
      alone in ventricular premature beat (VPB) patients (RR, 1.19, 95% CI: 1.05-1.34;
      P=0.005; I2=13%, P=0.32), and an improvement in quality-of-life score (QOLS) of
      VPB also showed in 1 individual study. Besides, a lower heart rate was detected
      in the CA alone group by 1 individual study when compared with no treatment in
      sinus tachycardia patients (MD-21.84 [-27.21,-16.47]) and lower adverse events of
      CA alone were reported than amiodarone. CONCLUSIONS: CA may be a useful and safe
      alternative or additive approach to AADs for cardiac arrhythmia, especially in
      VPB and Af patients, which mainly based on a pooled estimate and result from 1
      study with higher methodological quality. However, we could not reach a robust
      conclusion due to low quality of overall evidence.

PMID- 28432530
TI  - An integrated microsystem with dielectrophoresis enrichment and impedance
      detection for detection of Escherichia coli.
AB  - An integrated microsystem device with matched interdigitated microelectrode chip
      was fabricated for enrichment and detection of Escherichia coli O157:H7. The
      microsystem has integrated with positive dielectrophoresis (pDEP) enrichment and
      in situ impedance detection, whose total volume is only 3.0 * 10-3 m3, and could
      provide impedance testing voltages of 0 ~ 10 V, detection frequencies of 1 KHz ~
      1 MHz, DEP excitation signals with amplitude of 0 ~ 10 Vpp and frequencies of
      1KHz ~ 1 MHz, which fully meets the demands of pDEP enrichment and impedance
      detection for bacteria. The microfluidic chip with interdigitated microelectrodes
      was manufactured by microfabrication methods. The interdigital microelectrode
      array has sufficient contact area with a bacterial suspension to improve
      enrichment efficiency and detection sensitivity. Bacteria in the interdigital
      microelectrode area of the microfluidic chip were firstly captured and enriched
      by pDEP. Then, in situ impedance detection of the enriched bacteria was realized
      by switching test conditions. Using the self-assembly microsystem, a novel
      quantitative detection method was established and demonstrated to detect
      Escherichia coli O157:H7. Experimental results showed that the detection limits
      of Escherichia coli O157:H7 was 5 * 104 cfu mL-1, and testing time was only 6 min
      under the optimized detection voltage of 100 mV and frequency of 500 KHz. The
      method was successfully used to detect Escherichia coli O157:H7 in synthetic
      chicken synthetic samples.

PMID- 28432529
TI  - Ginseng-Derived Panaxadiol Saponins Promote Hematopoiesis Recovery in
      Cyclophosphamide-Induced Myelosuppressive Mice: Potential Novel Treatment of
      Chemotherapy-Induced Cytopenias.
AB  - OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component
      (PDS-C), a biologically active fraction isolated from total ginsenosides, to
      reverse chemotherapy-induced myelosuppression and pancytopenia caused by
      cyclophamide (CTX). METHODS: Mice with myelosuppression induced by CTX were
      treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80
      mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC),
      neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony
      formation were observed, the protein kinase and transcription factors in
      hematopoietic cells were determined by immunohistochemical staining and Western
      blot. RESULTS: In response to PDS-C therapy, the peripheral WBC, NEU and PLT
      counts of CTX-induced myelosuppressed mice were significantly increased in a dose
      dependent manner. Similarly, bone marrow histopathology examination showed
      reversal of CTX-induced myelosuppression with increase in overall bone marrow
      cellularity and the number of hematopoietic cells (P<0.01). PDS-C also promoted
      proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated
      mice, as evidenced by significantly increase in colony formation units
      granulocytes/monocytes and -megakaryocytes (P<0.01). The enhancement of
      hematopoiesis by PDS-C appears to be mediated by an intracellular signaling
      pathway, this was evidenced by the up-regulation of phosphorylated mitogen
      activated protein kinase (p-MEK) and extracellular signal-regulated kinases (p
      ERK), and receptor tyrosine kinase (C-kit) and globin transcription factor 1
      (GATA-1) in hematopoietic cells of CTX-treated mice (P<0.05). CONCLUSIONS: PDS-C
      possesses hematopoietic growth factor-like activities that promote proliferation
      and also possibly differentiation of hematopoietic progenitor cells in
      myelosuppressed mice, probably mediated by a mechanism involving MEK and ERK
      protein kinases, and C-kit and GATA-1 transcription factors. PDS-C may
      potentially be a novel treatment of myelosuppression and pancytopenia caused by
      chemotherapy.

PMID- 28432531
TI  - Effectiveness of nanoencapsulated methotrexate against osteosarcoma cells: in
      vitro cytotoxicity under dynamic conditions.
AB  - Cancer is a leading cause of mortality in the world, with osteosarcoma being one
      of the most common types among children between 1 and 14 years old. Current
      treatments including preoperative chemotherapy, surgery and postoperative
      chemotherapy produce several side effects with limited effectiveness. The use of
      lipid nanoparticles as biodegradable shells for controlled drug delivery shows
      promise as a more effective and targeted tumor treatment. However, in vitro
      validation of these vehicles is limited due to fluid stagnation in current
      techniques, in which nanoparticles sediment onto the bottom of the wells killing
      the cells by asphyxiation. In the current series of experiments, results obtained
      with methotrexate-lipid nanoparticles under dynamic assay conditions are
      presented as a promising alternative to current free drug based therapies.
      Effects on the viability of the U-2 OS osteosarcoma cell line of recirculation of
      cell media, free methotrexate and blank and methotrexate containing lipid
      nanoparticles in a 11 MUM concentration were successfully assessed. In addition,
      several designs for the microfluidic platform used were simulated using COMSOL
      Multiphysics, optimized devices were fabricated using soft-lithography and
      simulated parameters were experimentally validated. Nanoparticles did not
      sediment to the bottom of the platform, demonstrating the effectiveness of the
      proposed system. Moreover, encapsulated methotrexate was the most effective
      treatment, as after 72 h the cell population was reduced nearly 40% while under
      free methotrexate circulation the cell population doubled. Overall, these results
      indicate that methotrexate-lipid nanoparticles are a promising targeted therapy
      for osteosarcoma treatment.

PMID- 28432532
TI  - A portable battery powered microfluidic impedance cytometer with smartphone
      readout: towards personal health monitoring.
AB  - We present a portable system for personalized blood cell counting consisting of a
      microfluidic impedance cytometer and portable analog readout electronics, feeding
      into an analog-to-digital converter (ADC), and being transmitted via Bluetooth to
      a user-accessible mobile application. We fabricated a microfluidic impedance
      cytometer with a novel portable analog readout. The novel design of the analog
      readout, which consists of a lock-in-amplifier followed by a high-pass filter
      stage for subtraction of drift and DC offset, and a post-subtraction high gain
      stage, enables detection of particles and cells as small as 1 MUm in diameter,
      despite using a low-end 8-bit ADC. The lock-in-amplifier and the ADC were set up
      to receive and transmit data from a Bluetooth module. In order to initiate the
      system, as well as to transmit all of the data, a user friendly mobile
      application was developed, and a proof-of-concept trial was run on a blood
      sample. Applications such as personalized health monitoring require robust device
      operation and resilience to clogging. It is desirable to avoid using channels
      comparable in size to the particles being detected thus requiring high levels of
      sensitivity. Despite using low-end off-the-shelf hardware, our sensing platform
      was capable of detecting changes in impedance as small as 0.032%, allowing
      detection of 3 MUm diameter particles in a 300 MUm wide channel. The sensitivity
      of our system is comparable to that of a high-end bench-top impedance
      spectrometer when tested using the same sensors. The novel analog design allowed
      for an instrument with a footprint of less than 80 cm2. The aim of this work is
      to demonstrate the potential of using microfluidic impedance spectroscopy for low
      cost health monitoring. We demonstrated the utility of the platform technology
      towards cell counting, however, our platform is broadly applicable to assaying
      wide panels of biomarkers including proteins, nucleic acids, and various cell
      types.

PMID- 28432533
TI  - Erratum to: Deep Phenotyping of Systemic Arterial Hemodynamics in HFpEF (Part 1):
      Physiologic and Technical Considerations.

PMID- 28432534
TI  - Individual Differences in Adolescents' Emotional Reactivity across Relationship
      Contexts.
AB  - Understanding individual differences in adolescents' ability to regulate emotions
      within interpersonal relationships is paramount for healthy development. Thus,
      the effect of individual vulnerabilities (depressive affect, social anxiety, self
      blame, and coping efficacy problems) on the transmission of emotional reactivity
      in response to conflict from family to peers (friends and romantic partners) was
      prospectively examined across six waves of data in a community-based sample of
      416 adolescents (Mage Wave 1 = 11.90, 51% girls). Multiple-group models estimated
      in structural equation modeling suggested that youth who were higher in social
      anxiety or coping efficacy problems were more likely to transmit emotional
      reactivity developed in the family-of-origin to emotional reactivity in response
      to conflict in close friendships. Additionally, those youth higher in self-blame
      and depressive affect were more likely to transmit emotional reactivity from
      friendships to romantic relationships.

PMID- 28432536
TI  - Erratum to: A Qualitative Study to Explore the Views and Attitudes towards
      Prenatal Testing in Adults who Have Muenke Syndrome and their Partners.

PMID- 28432535
TI  - Exploring the Carbamazepine Interaction with Human Pregnane X Receptor and Effect
      on ABCC2 Using in Vitro and in Silico Approach.
AB  - PURPOSE: Over expression of ATP-binding cassette transporters is considered one
      of the major reasons for non-responsiveness to antiepileptic drugs. Carbamazepine
      (CBZ), one of first line antiepileptic drug is known to influence ABCC2
      expression but its exact molecular mechanism is unknown. METHODS: We investigated
      the effect of CBZ on expression of ABCC2 and pregnane X receptor (PXR) in HepG2
      cell line and compared with hyperforin (agonist of PXR) and ketoconazole
      (antagonist of PXR) through realtime PCR and western blot assay. Involvement of
      PXR was demonstrated through nuclear translocation and RNA interference and
      related effect of CBZ on ABCC2 through functional activity assay. Molecular
      docking and dynamic simulation approach was used to understand the interaction of
      CBZ with PXR. RESULTS: CBZ and hyperforin increased the PXR and ABCC2 expression
      whereas reversed when present it in combination with ketoconazole. Experiments
      confirmed CBZ induced ABCC2 expression is PXR dependent. Molecular dynamic (MD)
      simulation and in vitro experiment indicated possibility of CBZ to be PXR agonist
      and PXR residue Gln285 to be important for CBZ-PXR interaction. CONCLUSIONS: CBZ
      alters the functional activity of ABCC2 through PXR, which in turn can interfere
      with therapy. Mutational analysis of residues revealed the importance of Gln285
      in ligand interaction.

PMID- 28432537
TI  - Erratum to: Information Mismatch: Cancer Risk Counseling with Diverse Underserved
      Patients.

PMID- 28432538
TI  - Superoxide generated in the chloroplast stroma causes photoinhibition of
      photosystem I in the shade-establishing tree species Psychotria henryi.
AB  - Our previous studies indicated that high light induced significant
      photoinhibition of photosystem I (PSI) in the shade-establishing tree species
      Psychotria henryi. However, the underlying mechanism has not been fully
      clarified. In the present study, in order to investigate the mechanism of PSI
      photoinhibition in P. henryi, we treated detached leaves with constant high light
      in the presence of methyl viologen (MV) or a soluble alpha-tocopherol analog,
      2,2,5,7,8-pentamethyl-6-chromanol (PMC). We found that MV significantly depressed
      photochemical quantum yields in PSI and PSII when compared to PMC. On condition
      that no PSI photoinhibition happened, although cyclic electron flow (CEF) was
      abolished in the MV-treated samples, P700 oxidation ratio was maintain at higher
      levels than the PMC-treated samples. In the presence of PMC, PSI photoinhibition
      little changed but PSII photoinhibition was significantly alleviated.
      Importantly, PSI photoinhibition was largely accelerated in the presence of MV,
      which stimulates the production of superoxide and subsequently other reactive
      oxygen species at the chloroplast stroma by accepting electrons from PSI.
      Furthermore, MV largely aggravated PSII photoinhibition when compared to control.
      These results suggest that high P700 oxidation ratio cannot prevent PSI
      photoinhibition in P. henryi. Furthermore, the superoxide produced in the
      chloroplast stroma is critical for PSI photoinhibition in the higher plant P.
      henryi, which is opposite to the mechanism underlying PSI photoinhibition in
      Arabidopsis thaliana and spinach. These findings highlight a new mechanism of PSI
      photoinhibition in higher plants.

PMID- 28432540
TI  - Preliminary clinical study on non-transecting anastomotic bulbomembranous
      urethroplasty.
AB  - This study aims to investigate the effect of non-transecting anastomotic
      urethroplasty for treatment of posterior urethral stricture. A total of 23
      patients with traumatic posterior urethral stricture were enrolled and then
      divided into two groups. In one group, 12 patients underwent non-transecting
      anastomotic urethroplasty. In the other group, 11 patients underwent conventional
      posterior urethra end-to-end anastomosis. The effect of operation was evaluated
      using the following parameters: the bleeding amount during operation, operation
      time, IIEF-5 scores after operation, maximum flow rate (Qmax), and rating scale
      of quality of life (QoL). The comparison between the conventional posterior
      urethra end-to-end anastomosis group and the non-transecting anastomotic
      urethroplasty group showed no significant difference with regard to average
      operation time. However, a significant difference was observed between the groups
      with regard to the bleeding amount during operation. The patients in the group of
      non-transecting anastomotic urethroplasty urinated smoothly after the removal of
      catheter. Meanwhile, one patient from the group of conventional posterior urethra
      end-to-end anastomosis had difficulty urinating after the removal of catheter.
      Furthermore, significant differences in the operation time, bleeding amount
      during operation, IIEF-5 scores after operation, and rating scale of QoL were
      observed, whereas no significant difference was observed between urine flow rates
      of the two groups after operation. Overall, nontransecting anastomotic
      urethroplasty is effective for posterior urethra reconstruction, and it can
      reduce the occurrence rate of erectile dysfunction after operation.

PMID- 28432539
TI  - Early-Onset Ventilator-Associated Pneumonia in Patients with Severe Traumatic
      Brain Injury: Incidence, Risk Factors, and Consequences in Cerebral Oxygenation
      and Outcome.
AB  - BACKGROUND: Early-onset ventilator-associated pneumonia (EOVAP) occurs frequently
      in severe traumatic brain-injured patients, but potential consequences on
      cerebral oxygenation and outcome have been poorly studied. The objective of this
      study was to describe the incidence, risk factors for, and consequences on
      cerebral oxygenation and outcome of EOVAP after severe traumatic brain injury
      (TBI). METHODS: We conducted a retrospective, observational study including all
      intubated TBI admitted in the trauma center. An EOVAP was defined as a clinical
      pulmonary infection score >6, and then confirmed by an invasive method. Patient
      characteristics, computed tomography (CT) scan results, and outcome were
      extracted from a prospective register of all intubated TBI admitted in the
      intensive care unit (ICU). Data concerning the cerebral oxygenation monitoring by
      PbtO2 and characteristics of EOVAP were retrieved from patient files.
      Multivariate logistic regression models were developed to determine the risk
      factors of EOVAP and to describe the factors independently associated with poor
      outcome at 1-year follow-up. RESULTS: During 7 years, 175 patients with severe
      TBI were included. The overall incidence of EOVAP was 60.6% (47.4/1000 days of
      ventilation). Significant risk factors of EOVAP were: therapeutic hypothermia (OR
      3.4; 95% CI [1.2-10.0]), thoracic AIS score >=3 (OR 2.4; 95% CI [1.1-5.7]), and
      gastric aspiration (OR 5.2, 95% CI [1.7-15.9]). Prophylactic antibiotics
      administration was a protective factor against EOVAP (OR 0.3, 95% CI [0.1-0.8]).
      EOVAP had negative consequences on cerebral oxygenation. The PbtO2 was lower
      during EOVAP: 23.5 versus 26.4 mmHg (p <0.0001), and there were more brain
      hypoxia episodes: 32 versus 27% (p = 0.03). Finally, after adjusting for
      confounders, an EOVAP was an independent factor associated with unfavorable
      neurologic functional outcome at the 1-year follow-up (OR 2.71; 95% CI [1.01
      7.25]). CONCLUSIONS: EOVAP is frequent after a severe TBI (overall rate: 61%),
      with therapeutic hypothermia, severe thoracic lesion, and gastric aspiration as
      main risk factors. EOVAP had a negative impact on cerebral oxygenation measured
      by PbtO2 and was independently associated with unfavorable outcome at 1-year
      follow-up. This suggests that all precautions available should be taken to
      prevent EOVAP in this population.

PMID- 28432541
TI  - Genome characteristics of the proteorhodopsin-containing marine flavobacterium
      Polaribacter dokdonensis DSW-5.
AB  - Bacteria in the genus Polaribacter, belonging to the family Flavobacteriaceae,
      are typically isolated from marine environments. Polaribacter dokdonensis DSW-5,
      the type strain of the species, is a Gram-negative bacterium isolated from the
      East Sea of Korea. Whole genome shotgun sequencing was performed with the HiSeq
      2000 platform and paired-end reads were generated at 188-fold coverage. The
      sequencing reads were assembled into two contigs with a total length of 3.08 Mb.
      The genome sequences of DSW-5 contain 2,776 proteincoding sequences and 41 RNA
      genes. Comparison of average nucleotide identities among six available
      Polaribacteria genomes including DSW-5 suggested that the DSW-5 genome is most
      similar to that of Polaribacter sp. MED152, which is a proteorhodopsin-containing
      marine bacterium. A phylogenomic analysis of the six Polaribacter strains and 245
      Flavobacteriaceae bacteria confirmed a close relationship of the genus
      Polaribacter with Tenacibaculum and Kordia. DSW-5's genome has a gene encoding
      proteorhodopsin and genes encoding 85 enzymes belonging to carbohydrate-active
      enzyme families and involved in polysaccharide degradation, which may play
      important roles in energy metabolism of the bacterium in the marine ecosystem.
      With genes for 238 CAZymes and 203 peptidases, DSW-5 has a relatively high number
      of degrading enzymes for its genome size suggesting its characteristics as a free
      living marine heterotroph.

PMID- 28432542
TI  - Limb-shaking TIA: on the borders of evidence-based medicine.

PMID- 28432543
TI  - Understanding and improving decisions in clinical medicine (I): Reasoning,
      heuristics, and error.

PMID- 28432544
TI  - Expression of CphB- and CphE-type cyanophycinases in cyanophycin-producing
      tobacco and comparison of their ability to degrade cyanophycin in plant and plant
      extracts.
AB  - Increasing the arginine (Arg) content in plants used as feed or food is of
      interest, since the supplementation of food with conditionally essential Arg has
      been shown to have nutritional benefits. An increase was achieved by the
      expression of the Arg-rich bacterial storage component, cyanophycin (CGP), in the
      chloroplast of transgenic plants. CGP is stable in plants and its degradation
      into beta-aspartic acid (Asp)-Arg dipeptides, is solely catalyzed by bacterial
      cyanophycinases (CGPase). Dipeptides can be absorbed by animals even more
      efficiently than free amino acids (Matthews and Adibi 1976; Wenzel et al. 2001).
      The simultaneous production of CGP and CGPase in plants could be a source of beta
      Asp-Arg dipeptides if CGP degradation can be prevented in planta or if dipeptides
      are stable in the plants. We have shown for the first time that it is possible to
      co-express CGP and CGPase in the same plant without substrate degradation in
      planta by transient expression of the cyanobacterial CGPase CPHB (either in the
      plastid or cytosol), and the non-cyanobacterial CGPase CPHE (cytosol) in CGP
      producing Nicotiana tabacum plants. We compared their ability to degrade CGP in
      planta and in crude plant extracts. No CGP degradation appeared prior to cell
      homogenization independent of the CGPase produced. In crude plant extracts, only
      cytosolic CPHE led to a fast degradation of CGP. CPHE also showed higher
      stability and in vitro activity compared to both CPHB variants. This work is the
      next step to increase Arg in forage plants using a stable, Arg-rich storage
      protein.

PMID- 28432545
TI  - Genome edited animals: Learning from GM crops?
AB  - Genome editing of livestock is poised to become commercial reality, yet questions
      remain as to appropriate regulation, potential impact on the industry sector and
      public acceptability of products. This paper looks at how genome editing of
      livestock has attempted to learn some of the lessons from commercialisation of GM
      crops, and takes a systemic approach to explore some of the complexity and
      ambiguity in incorporating genome edited animals in a food production system.
      Current applications of genome editing are considered, viewed from the
      perspective of past technological applications. The question of what is genome
      editing, and can it be considered natural is examined. The implications of
      regulation on development of different sectors of livestock production systems
      are studied, with a particular focus on the veterinary sector. From an EU
      perspective, regulation of genome edited animals, although not necessarily the
      same as for GM crops, is advocated from a number of different perspectives. This
      paper aims to open up new avenues of research on genome edited animals, extending
      from the current primary focus on science and regulation, to engage with a wider
      range of food system actors.

PMID- 28432546
TI  - Affective, cognitive and behavioral outcomes associated with a false positive
      ovarian cancer screening test result.
AB  - While participation in cancer screening can facilitate early detection and
      improved prognosis, all screening tests yield some proportion of abnormal test
      results which are later determined benign. These false positive (FP) results can
      negatively impact affective, cognitive, and behavioral outcomes. Women
      participating in an ovarian cancer (OC) screening program receiving an abnormal
      screening test result (n = 375) were matched with women receiving normal results
      (n = 375). Both groups completed a baseline and 1- and 4-month follow-up
      assessments. FP test results were clearly associated with increased cancer
      specific distress and increased perceptions of OC risk with more limited evidence
      for increased perceived positive consequences of screening and increased
      intentions to participate in future OC screening. FP OC screening test results
      negatively impact both affective and cognitive outcomes which may serve to reduce
      motivation to participate in future routine screening. The development and
      testing of brief, timely interventions to minimize this negative impact is
      warranted.

PMID- 28432547
TI  - Health-Related Quality-of-Life and Diabetes Self-Care Activity in Elderly
      Patients with Diabetes in Korea.
AB  - A critical goal in the management of elderly patients with diabetes is to improve
      their health-related quality of life (HRQOL). This study aimed to identify the
      factors affecting HRQOL in elderly Korean patients with diabetes. Participants
      were 365 elderly patients with diabetes who were treated in a general hospital in
      Korea. The data were analysed using independent t-tests, Pearson correlations,
      and stepwise multiple regression. The mean total HRQOL score was 74.77, and HRQOL
      showed positive correlations with activities of daily living (ADL), instrumental
      activities of daily living (IADL), and the Summary of Diabetes Self-care
      Activities (SDSA). There was a negative correlation between HRQOL and Short
      Geriatric Depression Scale (SGDS). Lower SGDS scores, higher SDSA scores, and
      being male were associated with higher HRQOL, with these variables explaining
      57.5% of the variance in participants' HRQOL. Improvement in the HRQOL of elderly
      patients with diabetes requires the development of interventions for depression,
      and improvements in methods of diabetes self-care and gender-dependent managerial
      measures.

PMID- 28432548
TI  - Prostate Knowledge, Attitudes and Beliefs in Black College Men: A Qualitative
      Study.
AB  - This qualitative study explores prostate cancer knowledge and risk in Black
      college men. Using the Health Belief Model as a guide, focus groups and
      interviews were conducted with 35 Black males at a historically black college and
      university. Thematic analysis was conducted and general themes were found.
      Results indicate that Black college males have very little knowledge and
      understanding of what their prostate is and what it does. They are also unaware
      of their risk of developing prostate cancer. Additionally, while many believe
      prostate cancer is severe, few believe they are susceptible to getting it. These
      findings suggest more work needs to be done to educate young Black males on not
      only their prostate and prostate cancer, but on their general health. Efforts
      should focus on increasing the health knowledge of younger Black males in
      addition to that of middle-aged and older Black males so that health disparities
      can decrease.

PMID- 28432549
TI  - Factors Associated with HPV Vaccination in Young Males.
AB  - Human papilloma virus (HPV) affects both men and women; however, recommendations
      for HPV vaccination among men were not issued in the United States until 2011.
      The purpose of this study was to describe and compare characteristics of men who
      did and did not report receiving at least one dose of the HPV vaccine. Data from
      the ten states that completed the HPV vaccination module in the 2013 Behavioral
      Risk Factor Surveillance System (BRFSS) were included in the study. Young men
      ages 18-26 were included (N = 1624). Categorical variables were compared between
      those who did and did not receive the HPV vaccine using Chi square. Logistic
      regression was used to examine the odds of HPV vaccination by the above factors.
      Only 16.5% of men reported at least one dose of HPV vaccine. Having health
      insurance, having a primary doctor, and receiving an HIV test were predictive of
      HPV vaccination. Men in Texas were more likely to report HPV vaccination than all
      other states. Overall, HPV vaccination is low in men. Targeted interventions for
      improving HPV vaccination rates in men are warranted, especially for those
      without health insurance or a routine source of care.

PMID- 28432550
TI  - Estradiol mitigates ischemia reperfusion-induced acute renal failure through NMDA
      receptor antagonism in rats.
AB  - In the present study, we investigated possible involvement of N-methyl-D
      aspartate receptors (NMDAR) in estradiol mediated protection against ischemia
      reperfusion (I/R)-induced acute renal failure (ARF) in rats. Bilateral renal
      ischemia of 40 min followed by reperfusion for 24 h induced ARF in male wistar
      rats. Quantification of serum creatinine, creatinine clearance (CrCl), blood urea
      nitrogen (BUN), uric acid, potassium, fractional excretion of sodium (FeNa), and
      urinary microproteins was done to assess I/R-induced renal damage in rats.
      Oxidative stress in kidneys was measured in terms of myeloperoxidase activity,
      thiobarbituric acid reactive substances, superoxide anion generation, and reduced
      glutathione levels. Hematoxylin & eosin and periodic acid Schiff stains were used
      to reveal structural changes in renal tissues. Estradiol benzoate (0.5 and 1.0
      mg/kg, intraperitoneally, i.p.) was administered 1 h prior to I/R in rats. In
      separate groups, rats were treated with NMDAR agonists, glutamic acid (200 mg/kg,
      i.p.), and spermidine (20 mg/kg, i.p.) before administration of estradiol. Marked
      increase in serum creatinine, BUN, uric acid, serum potassium, FeNa,
      microproteinuria, and reduction in CrCl demonstrated I/R-induced ARF in rats.
      Treatment with estradiol mitigated I/R-induced changes in serum/urine parameters.
      Moreover, estrogen attenuated oxidative stress and structural changes in renal
      tissues. Prior administration of glutamic acid and spermidine abolished estradiol
      mediated renoprotection in rats. These results indicate the involvement of NMDAR
      in estradiol mediated renoprotective effect. In conclusion, we suggest that NMDAR
      antagonism serves as one of the mechanisms in estradiol-mediated protection
      against I/R-induced ARF in rats.

PMID- 28432551
TI  - Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells.
AB  - The bacterial antibiotic anisomycin is known to induce apoptosis by activating
      several mitogen-activated protein kinases and by inhibiting protein synthesis. In
      this study, the influence of p53 protein on the apoptosis-inducing effect of
      anisomycin was investigated. The effect of protein synthesis-inhibiting
      concentration of anisomycin on apoptotic events was analyzed using Western blot,
      DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53
      protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic
      pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to
      the drug than their wild-type counterparts. Anisomycin caused the activation of
      the main stress kinases, phosphorylation of the p53 protein and the eukaryotic
      initiation factor eIF2alpha, proteolytic cleavage of protein kinase R, Bid,
      caspase-9 and -3. Furthermore, anisomycin treatment led to the activation of
      TRAIL and caspase-8, two proteins involved in the extrinsic apoptotic pathway.
      All these changes were stronger and more sustained in wtPC12 cells. In the
      presence of the dominant inhibitory p53 protein, p53- dependent genes involved in
      the regulation of apoptosis may be less transcribed and this can lead to the
      decrease of apoptotic processes in p143p53PC12 cells.

PMID- 28432552
TI  - Subchronic nandrolone administration reduces cardiac oxidative markers during
      restraint stress by modulating protein expression patterns.
AB  - Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in
      collegiate and professional sports, is associated with detrimental cardiovascular
      effects through redox-dependent mechanisms. We previously observed that high-dose
      short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart
      ventricular hypertrophy and, paradoxically, improved postischemic response,
      whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly
      reduced the cardioprotective effect of postconditioning, with an increase in
      infarct size and a decrease in cardiac performance. We wanted to determine
      whether short-term ND administration could affect the oxidative redox status in
      animals exposed to acute restraint stress. Our hypothesis was that, depending on
      treatment schedule, ND may have a double-edged sword effect. Measurement of
      malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma
      and left heart ventricular tissue, revealed that the levels of both markers were
      increased in animals exposed to restraint stress, whereas no increase in marker
      levels was noted in animals pretreated with ND, indicating a possible protective
      action of ND against stress-induced oxidative damage. Furthermore, isolation and
      identification of proteins extracted from the left heart ventricular tissue
      samples of rats pretreated or not with ND and exposed to acute stress showed a
      prevalent expression of enzymes involved in amino acid synthesis and energy
      metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both
      involved in the oxidative stress response, were predominantly expressed in the
      left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems
      to reduce oxidative stress by inducing the expression of antioxidant proteins in
      the hearts of restraint-stressed animals, thus contributing to amelioration of
      postischemic heart performance.

PMID- 28432553
TI  - Cardiolipin deficiency causes triacylglycerol accumulation in Saccharomyces
      cerevisiae.
AB  - In yeast, the synthesis of cardiolipin (CL) and phosphatidylethanolamine (PE)
      occurs mainly in mitochondria. CL and PE have overlapping functions, and they are
      required for mitochondrial function. PE is physiologically linked with
      triacylglycerol (TAG) metabolism in Saccharomyces cerevisiae, involving an acyl
      CoA-independent pathway through the phospholipid:diacylglycerol acyltransferase
      activity of the Lro1 protein. There is no report on the physiological link
      between CL and TAG metabolism. Here we report a metabolic link between CL and TAG
      accumulation in the S. cerevisiae. Our data indicated that CL deficiency causes
      TAG accumulation, involving an acyl-CoA-dependent pathway through the
      diacylglycerol acyltransferase activity of the Dga1 protein with no changes in
      the TAG molecular species. The DGA1 gene deletion from the CL-deficient strains
      reduced the TAG levels. Data from in vitro and in vivo analyses showed that CL
      did not affect the enzymatic activity of Dga1. Our data also showed that CL
      deficiency leads to the up-regulation of acetyl-CoA synthetase genes (ACS1 and
      ACS2) of the cytosolic pyruvate dehydrogenase bypass pathway. This study
      establishes a physiological link between CL and TAG metabolism in S. cerevisiae.

PMID- 28432554
TI  - Epigallocatechin gallate protects BEAS-2B cells from lipopolysaccharide-induced
      apoptosis through upregulation of gastrin-releasing peptide.
AB  - Gastrin-releasing peptide (GRP) plays a major role in the development and
      maintenance of lung epithelial cells by promoting cell division, whereas its
      suppression causes growth arrest and apoptosis. The present study shows that
      human bronchial epithelial BEAS-2B cells challenged with lipopolysaccharide
      (LPS), an endotoxin from gram-negative bacteria, downregulated GRP expression and
      induced apoptosis via upregulation of p53 and active caspase-3, signifying the
      importance of GRP in lung epithelial cell survival. However, in the presence of
      epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, BEAS-2B cells
      resisted LPS-induced apoptosis and restored the expression of GRP and its
      downstream effectors such as epidermal growth factor receptor and NF-kappaB, as
      analysed by immunoblotting and qPCR. Based on our findings, we objectify that
      cytoprotective functions of EGCG, via upregulation of GRP in cells challenged
      with LPS, are novel and can be further explored in a therapeutic point of view
      for diseases such as septic shock.

PMID- 28432555
TI  - Rotundarpene inhibits TNF-alpha-induced activation of the Akt, mTOR, and NF
      kappaB pathways, and the JNK and p38 associated with production of reactive
      oxygen species.
AB  - Ilex Rotunda Thunb has been shown to have anti-inflammatory and antioxidant
      effects. In human keratinocytes, we investigated the effect of rotundarpene (4
      caffeoyl-3-methyl-but-2-ene-1,4-diol) on the TNF-alpha-stimulated production of
      inflammatory mediators in relation to the Akt, mTOR, and NF-kappaB pathways, and
      the JNK and p38-MAPK. Rotundarpene, Akt inhibitor, Bay 11-7085, rapamycin, and N
      acetylcysteine inhibited the TNF-alpha-stimulated production of cytokines and
      chemokines, increase in the levels of p-Akt and mTOR, activation of NF-kappaB,
      and production of reactive oxygen species in keratinocytes. TNF-alpha treatment
      induced phosphorylation of the JNK and p38-MAPK. Inhibitors of the c-JNK
      (SP600125) and p38-MAPK (SB203580) reduced the TNF-alpha-induced production of
      inflammatory mediators, binding of NF-kappaB to DNA, and activation of the JNK
      and p38-MAPK in keratinocytes. The results show that rotundarpene may reduce the
      TNF-alpha-stimulated inflammatory mediator production by suppressing the reactive
      oxygen species-dependent activation of the Akt, mTOR, and NF-kappaB pathways, and
      activation of the JNK and p38-MAPK in human keratinocytes. Additionally,
      rotundarpene appears to attenuate the Akt, mTOR, and NF-kappaB pathways and the
      JNK and p38-MAPK-mediated inflammatory skin diseases.

PMID- 28432556
TI  - Enzymes that hydrolyze adenine nucleotides in a model of hypercholesterolemia
      induced by Triton WR-1339: protective effects of beta-caryophyllene.
AB  - Purinergic system has been proven to play a critical role in the inflammatory
      process and to represent an important therapeutic target to improve the immune
      response during hypercholesterolemia. beta-caryophyllene, a phytocannabinoid
      compound, has a powerful hypolipidemic and anti-inflammatory actions. However,
      the effects of beta-caryophyllene on seric enzymes of purinergic system have not
      been evaluated. The purpose of this study was to investigate whether beta
      caryophyllene is able to ameliorate the seric activities of NTPDase and adenosine
      deaminase (ADA) in a model of hypercholesterolemia induced by Triton WR-1339. The
      activities of NTPDase and ADA were evaluated enzymatically, and the seric levels
      of beta-caryophyllene were evaluated by high-performance liquid chromatography.
      We found that treatment with beta-caryophyllene ameliorates the enzymatic
      activities of NTPDase and ADA in serum of hypercholesterolemic rats, in a
      concentration-dependent manner. These results indicated that beta-caryophyllene
      treatment could improve the immune response during hypercholesterolemia through
      purinergic pathway.

PMID- 28432559
TI  - The Marriage Wealth Premium Revisited: Gender Disparities and Within-Individual
      Changes in Personal Wealth in Germany.
AB  - This study examines the association between marriage and economic wealth of women
      and men. Going beyond previous research that focused on household wealth, I
      examine personal wealth, which allows identifying gender disparities in the
      association between marriage and wealth. Using unique data from the German Socio
      Economic Panel Study (2002, 2007, and 2012), I apply random-effects and fixed
      effects regression models to test my expectations. I find that both women and men
      experience substantial marriage wealth premiums not only in household wealth but
      also in personal wealth. However, I do not find consistent evidence for gender
      disparities in these general marriage premiums. Additional analyses indicate,
      however, that women's marriage premiums are substantially lower than men's
      premiums in older cohorts and when only nonhousing wealth is considered. Overall,
      this study provides new evidence that women and men gain unequally in their
      wealth attainment through marriage.

PMID- 28432557
TI  - Proteomic analysis of mitochondrial proteins in the guinea pig heart following
      long-term normobaric hyperoxia.
AB  - Normobaric hyperoxia is applied for the treatment of a wide variety of diseases
      and clinical conditions related to ischemia or hypoxia, but it can increase the
      risk of tissue damage and its efficiency is controversial. In the present study,
      we analyzed cardiac mitochondrial proteome derived from guinea pigs after 60 h
      exposure to 100% molecular oxygen (NBO) or O2 enriched with oxygen cation (NBO+).
      Two-dimensional gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry
      identified twenty-two different proteins (among them ten nonmitochondrial) that
      were overexpressed in NBO and/or NBO+ group. Identified proteins were mainly
      involved in cellular energy metabolism (tricarboxylic acid cycle, oxidative
      phosphorylation, glycolysis), cardioprotection against stress, control of
      mitochondrial function, muscle contraction, and oxygen transport. These findings
      support the viewpoint that hyperoxia is associated with cellular stress and
      suggest complex adaptive responses which probably contribute to maintain or
      improve intracellular ATP levels and contractile function of cardiomyocytes. In
      addition, the results suggest that hyperoxia-induced cellular stress may be
      partially attenuated by utilization of NBO+ treatment.

PMID- 28432558
TI  - Resolved Parental Infertility and Children's Educational Achievement.
AB  - Although difficulty conceiving a child has long been a major medical and social
      preoccupation, it has not been considered as a predictor of long-term outcomes in
      children ultimately conceived. This is consistent with a broader gap in knowledge
      regarding the consequences of parental health for educational performance in
      offspring. Here we address that omission, asking how resolved parental
      infertility relates to children's academic achievement. In a sample of all
      Swedish births between 1988 and 1995, we find that involuntary childlessness
      prior to either a first or a second birth is associated with lower academic
      achievement (both test scores and GPA) in children at age 16, even if the period
      of infertility was prior to a sibling's birth rather than the child's own. Our
      results support a conceptualization of infertility as a cumulative physical and
      social experience with effects extending well beyond the point at which a child
      is born, and emphasize the need to better understand how specific parental health
      conditions constrain children's educational outcomes.

PMID- 28432560
TI  - Executive function and life-space mobility in old age.
AB  - BACKGROUND: Life-space assessment incorporates all movements in terms of the
      distance from home, the frequency of movement and the need of assistance for
      movement. Executive function (EF) is an important higher order cognitive ability
      that controls and guides people's goal-directed actions. We examined the cross
      sectional and longitudinal associations between EF and life-space mobility, and
      investigated if perceived walking difficulties, lower extremity performance, and
      transportation difficulties explain the association. METHODS: 157 community
      dwelling persons aged 76-91 years participated in the study at the baseline, and
      103 of them in 2-year follow-up study. Based on the distribution on the Trail
      Making Test participants were categorized into tertiles of EF. Life-space
      mobility was assessed using the Life-Space Assessment (range 0-120). Perceived
      walking difficulties and transportation difficulties were self-reported, and
      lower extremity performance was assessed with the short physical performance
      battery (SPPB). Adjustments were made for gender, age, number of chronic
      conditions, and years of education. RESULTS: Average age of participants at the
      baseline was 82.6 (SD 4.2) years and 61% were women. Individuals with poor EF had
      lower life-space mobility compared to those with good EF. SPPB and transportation
      difficulties explained the association. Over the 2-year follow-up, those with
      poor EF at the baseline showed steeper decline but the difference did not quite
      reach statistical significance (p = 0.068). CONCLUSIONS: People with better
      executive function had higher life-space mobility. This was explained by better
      lower extremity performance and absence of transportation difficulties. Cognitive
      decline may hinder access to community amenities, which in turn may further
      accelerate cognitive decline.

PMID- 28432561
TI  - Predicting fluid responsiveness in whom? A simulated example of patient spectrum
      influencing the receiver operating characteristics curve.
AB  - The influence of patient spectrum on the sensitivities and specificities of
      diagnostic methods has been termed spectrum bias or spectrum effect. Receiver
      operating characteristics curves are often used to assess the ability of
      diagnostic methods to predict fluid responsiveness. As a receiver operating
      characteristics curve is a presentation of sensitivity and specificity, the
      purpose of the present manuscript was to explore if patient spectrum could affect
      areas under receiver operating characteristics curves and their gray zones.
      Relationships between stroke volume variation and change in stroke volume in two
      different patient populations using simulated data. Simulated patient populations
      with stroke volume variation values between 5 and 15 or 3 and 25% had median
      (2.5th-97.5th percentiles) areas under receiver operating characteristics curves
      of 0.79 (0.65-0.90) and 0.93 (0.85-0.99), respectively. The gray zones indicating
      range of diagnostic uncertainty were also affected. The patient spectrum can
      affect common statistics from receiver operating characteristics curves,
      indicating the need for considering patient spectrum when evaluating the
      abilities of different methods to predict fluid responsiveness.

PMID- 28432563
TI  - Complete sequences of the RNA 1 and RNA 2 segments of chronic bee paralysis virus
      strain CBPV-BJ detected in China.
AB  - Chronic bee paralysis virus (CBPV) is an important viral pathogen that affects
      adult bees. Although several CBPV strains have been reported, little information
      has been obtained from China. In this study, two major segments of the CBPV
      Chinese isolate CBPV-BJ, RNA 1 and RNA 2, were determined to be 3657 and 2267
      nucleotides (nt) in length, respectively. RNA 1 and RNA 2 contained three and
      four open reading frames (ORFs), respectively, which agreed with known reference
      strains (EU122229 and EU122230). The RNA 1 had 98% nucleotide sequence identity
      to a known Chinese strain (KU950353), and RNA 2 had 97% nucleotide sequence
      identity to another Chinese strain (KU950354). Although the lengths of the RNA 1
      and RNA 2 sequences were 17 nt and 38 nt shorter than those of the CBPV reference
      strains EU122229 and EU122230, respectively, the complete CBPV-BJ RNA 1 and RNA 2
      sequences shared 91% and 92% identity with them. Phylogenetic analysis based on
      the sequences of the RNA-dependent RNA polymerase (RdRp) and putative structural
      proteins (pSPs) showed that CBPV-BJ was most closely related to the other two
      Chinese isolate (KU950353 and KU950354) and clustered with most Asian strains.
      These data provide new information that will lead to a better understanding of
      the diversity of the CBPV genome.

PMID- 28432562
TI  - Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in
      corticotroph pituitary adenomas is associated with tumor invasion and Crooke's
      cell morphology.
AB  - PURPOSE: MCM7 (minichromosome maintenance complex component 7), a DNA replication
      licensing factor, is a host gene for the oncogenic miR-106b~25 cluster. It has
      been recently revealed as a relevant prognostic biomarker in a variety of
      cancers, including pituitary adenomas. The purpose of this study was to assess
      whether miR-106b~25 and MCM7 levels correlate with tumor invasiveness in a cohort
      of ACTH-immunopositive adenomas. METHODS: Tissue samples were obtained
      intraoperatively from 25 patients with pituitary adenoma. Tumor invasiveness was
      assessed according to the Knosp grading scale. MCM7, Ki-67 and TP53 levels were
      assessed by immunohistochemical staining, while the expression of miR-106b-5p,
      miR-93-5p, miR-93-3p and miR-25-3p were measured using quantitative real-time PCR
      performed on RNA isolated from FFPE tissues. RESULTS: We have found a significant
      increase in MCM7 and Ki-67 labeling indices in invasive ACTHomas. Moreover, MCM7
      was ubiquitously overexpressed in Crooke's cell adenomas. The expression of miR
      93-5p was significantly elevated in invasive compared to noninvasive tumors. In
      addition, all four microRNAs from the miR-106b~25 cluster displayed marked
      upregulation in Crooke's cell adenomas. Remarkably, MCM7 and miR-106b-5p both
      strongly correlated with Knosp grade. A combination of MCM7 LI and miR-106b~25
      cluster expression was able to accurately differentiate invasive from noninvasive
      tumors and had a significant discriminatory ability to predict postoperative
      tumor recurrence/progression. CONCLUSIONS: miR-106b~25 and its host gene MCM7 are
      potential novel biomarkers for invasive ACTH-immunopositive pituitary adenomas.
      Additionally, they are both significantly upregulated in rare Crooke's cell
      adenomas and might therefore contribute to their aggressive phenotype.

PMID- 28432564
TI  - Unintended Pregnancy and Contraceptive Use Among Women Veterans: The ECUUN Study.
AB  - BACKGROUND: Little is known about contraceptive care for the growing population
      of women veterans who receive care in the Veterans Administration (VA) healthcare
      system. OBJECTIVE: To determine rates of contraceptive use, unmet need for
      prescription contraception, and unintended pregnancy among reproductive-aged
      women veterans. DESIGN AND PARTICIPANTS: We conducted a cross-sectional,
      telephone-based survey with a national sample of 2302 women veterans aged 18-44
      years who had received primary care in the VA within the prior 12 months. MAIN
      MEASURES: Descriptive statistics were used to estimate rates of contraceptive use
      and unintended pregnancy in the total sample. We also estimated the unmet need
      for prescription contraception in the subset of women at risk for unintended
      pregnancy. For comparison, we calculated age-adjusted US population estimates
      using data from the 2011-2013 National Survey of Family Growth (NSFG). KEY
      RESULTS: Overall, 62% of women veterans reported current use of contraception,
      compared to 68% of women in the age-adjusted US population. Among the subset of
      women at risk for unintended pregnancy, 27% of women veterans were not using
      prescription contraception, compared to 30% in the US population. Among women
      veterans, the annual unintended pregnancy rate was 26 per 1000 women; 37% of
      pregnancies were unintended. In the age-adjusted US population, the annual rate
      of unintended pregnancy was 34 per 1000 women; 35% of pregnancies were
      unintended. CONCLUSIONS: While rates of contraceptive use, unmet contraceptive
      need, and unintended pregnancy among women veterans served by the VA are similar
      to those in the US population, these rates are suboptimal in both populations,
      with over a quarter of women who are at risk for unintended pregnancy not using
      prescription contraception, and unintended pregnancies accounting for over a
      third of all pregnancies. Efforts to improve contraceptive service delivery and
      to reduce unintended pregnancy are needed for both veteran and civilian
      populations.

PMID- 28432565
TI  - Parapharyngodon hugoi n. sp., a new nematode (Oxyuroidea: Pharyngodonidae) of the
      tree frog Trachycephalus typhonius (Linnaeus) from the Brazilian Pantanal,
      including a key to the congeners from amphibians of the American continent.
AB  - A new nematode Parapharyngodon hugoi n. sp. (Oxyuroidea: Pharyngodonidae) is
      described parasitising the large intestine of the tree frog Trachycephalus
      typhonius (Linnaeus) (Anura: Hylidae) from the wetlands of Pantanal, State of
      Mato Grosso do Sul, Brazil. The new species exhibits a unique structure of the
      posterior cloacal lip in males, which is supported by a rigid V-shaped structure.
      Parapharyngodon hylidae parasitic in hylid frogs, including T. typhonius, from
      Mexico, is the most similar congener to P. hugoi n. sp. but is distinguished from
      the new species by the presence of a gubernaculum (vs absence), by the lateral
      alae in males ending far anterior to cloacal opening (vs near to it) and because
      in gravid females the ovaries encircle the oesophageal corpus. Additionally, the
      new species differs from its congeners as well as from species of Thelandros
      Wedl, 1862, a very closely related genus, by the combination of features such as
      spicule length, number of caudal papillae, morphology of the anterior cloacal
      lip, which is echinate, and position of ovaries. The geographical distribution of
      hosts seems to play an important role in the speciation process of
      Parapharyngodon spp.; however, due the lack of molecular data this issue along
      with the validity of both Thelandros and Parapharyngodon are still questions to
      be solved in the future, after improvement of the genetic database. A key to the
      species of Parapharyngodon parasitic in amphibians from the American continent is
      provided.

PMID- 28432566
TI  - Four new species of Dactylogyrus Diesing, 1850 (Monogenea: Dactylogyridae)
      parasitising the gills of northern Moroccan Luciobarbus Heckel (Cyprinidae):
      morphological and molecular characterisation.
AB  - Four new species of Dactylogyrus Diesing, 1850 are described from the gills of
      three species of Luciobarbus Heckel collected from various hydrographical basins
      in northern Morocco: Dactylogyrus scorpius n. sp. from Luciobarbus rifensis
      Doadrio, Casal-Lopez & Yahyaoui; D. benhoussai n. sp. from L. moulouyensis
      Pellegrin; and D. varius n. sp. and D. falsiphallus n. sp. from L. maghrebensis
      Doadrio, Perea & Yahyaoui. The descriptions of the new species are confirmed by
      molecular data (partial 18S rDNA, ITS1, and partial 28S rDNA sequences). All four
      species belong to the group of Dactylogyrus species, possessing a cross-shaped
      ventral bar and a male copulatory organ composed of a loosely coiled copulatory
      tube and an accessory piece with a capsule-like base and recurved distal portion.
      Given the high shape variability of the haptoral anchors reported among specimens
      of D. varius n. sp., three morphological forms within this species (D. varius f.
      vulgaris, D. varius f. magnus, and D. varius f. dromedarius) are recognised.
      However, specimens belonging to D. benhoussai n. sp. and D. varius f. vulgaris
      were morphologically very similar and were discriminated with certainty, only
      when using molecular data.

PMID- 28432568
TI  - The MUSOS (MUsic SOftware System) Toolkit: A computer-based, open source
      application for testing memory for melodies.
AB  - Despite numerous innovative studies, rates of replication in the field of music
      psychology are extremely low (Frieler et al., 2013). Two key methodological
      challenges affecting researchers wishing to administer and reproduce studies in
      music cognition are the difficulty of measuring musical responses, particularly
      when conducting free-recall studies, and access to a reliable set of novel
      stimuli unrestricted by copyright or licensing issues. In this article, we
      propose a solution for these challenges in computer-based administration. We
      present a computer-based application for testing memory for melodies. Created
      using the software Max/MSP (Cycling '74, 2014a), the MUSOS (Music Software
      System) Toolkit uses a simple modular framework configurable for testing common
      paradigms such as recall, old-new recognition, and stem completion. The program
      is accompanied by a stimulus set of 156 novel, copyright-free melodies, in audio
      and Max/MSP file formats. Two pilot tests were conducted to establish the
      properties of the accompanying stimulus set that are relevant to music cognition
      and general memory research. By using this software, a researcher without
      specialist musical training may administer and accurately measure responses from
      common paradigms used in the study of memory for music.

PMID- 28432567
TI  - Less approach, more avoidance: Response inhibition has motivational consequences
      for sexual stimuli that reflect changes in affective value not a lingering global
      brake on behavior.
AB  - Response inhibition negatively impacts subsequent hedonic evaluations of
      motivationally relevant stimuli and reduces the behavioral incentive to seek and
      obtain such items. Here we expand the investigation of the motivational
      consequences of inhibition by presenting sexually appealing and nonappealing
      images in a go/no-go task and a subsequent image-viewing task. Each initially
      obscured image in the viewing task could either be made more visible or less
      visible by repeatedly pressing different keys. Fewer key presses were made to
      obtain better views of preferred-sex images when such images had previously been
      inhibited as no-go items than when previously encountered as noninhibited go
      items. This finding replicates prior results and is consistent with the
      possibility that motor-response suppression has lingering effects that include
      global reductions in all behavioral expression. However, for nonpreferred images,
      prior inhibition resulted in more key presses to obscure their visibility than
      when such images had not been inhibited. This novel finding suggests that the
      motivational consequences of response inhibition are not due to a global brake on
      action but are instead linked to negative changes in stimulus value that induce
      corresponding increases in avoidance and decreases in approach.

PMID- 28432569
TI  - Are multiple-trial experiments appropriate for eyewitness identification studies?
      Accuracy, choosing, and confidence across trials.
AB  - Eyewitness identification experiments typically involve a single trial: A
      participant views an event and subsequently makes a lineup decision. As compared
      to this single-trial paradigm, multiple-trial designs are more efficient, but
      significantly reduce ecological validity and may affect the strategies that
      participants use to make lineup decisions. We examined the effects of a number of
      forensically relevant variables (i.e., memory strength, type of disguise, degree
      of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence
      across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376
      lineup decisions). The rates of correct rejections and choosing (across both
      target-present and target-absent lineups) did not vary across the 24 trials, as
      reflected by main effects or interactions with trial number. Trial number had a
      significant but trivial quadratic effect on correct identifications (OR = 0.99)
      and interacted significantly, but again trivially, with disguise type (OR =
      1.00). Trial number did not significantly influence participants' confidence in
      correct identifications, confidence in correct rejections, or confidence in
      target-absent selections. Thus, multiple-trial designs appear to have minimal
      effects on eyewitness accuracy, choosing, and confidence. Researchers should thus
      consider using multiple-trial designs for conducting eyewitness identification
      experiments.

PMID- 28432570
TI  - Vascular and Endothelial Function in Youth with Type 2 Diabetes Mellitus.
AB  - PURPOSE OF REVIEW: This review aims to discuss the burden of type 2 diabetes in
      youth and summarize the studies that have utilized noninvasive techniques to
      assess early vascular disease in youth with type 2 diabetes. RECENT FINDINGS:
      Noninvasive imaging modalities provide researchers with tools to investigate the
      vasculature in adolescents with type 2 diabetes. The data published to date
      consistently show adolescents with type 2 diabetes have greater vascular
      thickness and stiffness and worse endothelial function compared to their obese
      and lean peers. As the prevalence of type 2 diabetes continues to increase
      adolescent youth, there is concern adolescents with type 2 diabetes are at risk
      to develop early onset cardiovascular disease and complications. Future studies
      need to address treatments that have the potential to improve or reverse vascular
      dysfunction and decrease the rate of cardiovascular disease and complications.

PMID- 28432571
TI  - Cell Therapy for Type 1 Diabetes: Current and Future Strategies.
AB  - PURPOSE OF THE REVIEW: Type 1 diabetes (T1D) is defined by an autoimmune
      destruction of insulin producing beta-cells located in the endocrine part of the
      pancreas, the islets of Langerhans. As exogenous insulin administration fails at
      preventing severe complications associated with this disease, cell replacement
      therapies are being considered as a means to treat T1D. The purpose of this
      manuscript is to review the challenges associated with current strategies and
      discuss the potential of stem cell therapy for the treatment of T1D. RECENT
      FINDINGS: The most prominent therapy offered to T1D patients is exogenous insulin
      administration which, despite formulations improvement, remains a suboptimal
      treatment, due to the frequency of injections and the issues associated with
      precise dosing. As immunotherapy approaches have remained unsuccessful, the only
      cure for T1D is transplantation of donor-derived pancreas or islets. However,
      donor scarcity, graft loss, and immune response to the foreign tissue are issues
      challenging this approach and limiting the number of patients who can benefit
      from such treatments. In this review, we discuss the causes of T1D and the
      shortcomings of the current treatments. Furthermore, we summarize the cutting
      edge research that aims to tackle the current challenges in reaching a quality
      controlled product with long-term effects, with a focus on regenerative medicine
      approaches using human pluripotent stem cells.

PMID- 28432572
TI  - Micropapillary bladder cancer: a clinico-pathological characterization and
      treatment analysis.
AB  - PURPOSE: Micropapillary bladder cancer (MPBC) is a very rare and aggressive
      variant of urothelial carcinoma (UC). The aim of this study was to investigate
      the clinico-pathological characteristics, treatment, and prognosis of MPBC to
      improve the understanding of this invasive disease. METHODS: We reviewed the
      records of 6 patients with MPBC who were evaluated and treated at our hospital
      between 2009 and 2015, and additionally reviewed 38 cases reported in the
      literature. RESULTS: In 44 cases, 36 cases (81.8%) were male and 8 cases (18.2%)
      were female, with a male:female ratio of 4.5:1; the median age of the patients
      was 68 years (range 45-91 years). A majority (81.8%) of patients with cT1 above
      or with lymph node and distant metastasis (cT2N0 in 18.2%, cT3-4N0 in 13.6%,
      cTanyN+ in 43.2%, and cTanyM+ in 6.8%). There was a high grade in 70.5% of
      patients. Lymphovascular invasion (LVI) was present in 61.4% of patients, and LVI
      in cT2 was more common than in cT1 (71.4 vs 22.2%). 52.3% of patients were
      treated with radical cystectomy (RC). After a mean follow-up of 16.2 months,
      77.3% of patients developed distant metastases, and 47.7% of patients died of the
      disease. The mean overall survival (OS) was 28.9 months and the median OS was 20
      months, and the amount of micropapillary (MPP) is correlated inversely with
      prognosis. CONCLUSIONS: Micropapillary bladder cancer is a rare variant of UC
      associated with a poor prognosis, which often presents at an advanced stage with
      LVI and distant metastases. The optimal treatment strategy is early RC combined
      with chemotherapy.

PMID- 28432573
TI  - Clinical Outcomes in Trials Evaluating Lipid-Lowering Drugs.
AB  - While statins have formed the cornerstone of strategies for cardiovascular
      prevention, the residual risk related to low-density lipoprotein cholesterol (LDL
      C) and other lipoprotein factors provides a landscape for development of new
      therapies. However, a number of lipid-modifying therapies have failed to reduce
      cardiovascular event rates in contemporary clinical trials of statin-treated
      patients. The factors considered in outcome measure selection for clinical trials
      of novel lipid-lowering therapies are reviewed. Evaluation of lipid-modifying
      drugs in clinical trials spans a spectrum from their effects on conventional
      circulating lipid parameters through to their impact on atherosclerotic plaque
      and ultimately clinical outcomes. The design of these trials has an important
      impact on the result and ultimate interpretation of these studies.

PMID- 28432574
TI  - A critical appraisal of the quality of adult dual-energy X-ray absorptiometry
      guidelines in osteoporosis using the AGREE II tool: An EuroAIM initiative.
AB  - OBJECTIVES: Dual energy X-ray absorptiometry (DXA) is the most widely used
      technique to measure bone mineral density (BMD). Appropriate and accurate use of
      DXA is of great importance, and several guidelines have been developed in the
      last years. Our aim was to evaluate the quality of published guidelines on DXA
      for adults. METHODS: Between June and July 2016 we conducted an online search for
      DXA guidelines, which were evaluated by four independent readers blinded to each
      other using the AGREE II instrument. A fifth independent reviewer calculated
      scores per each domain and agreement between reviewers' scores. RESULTS: Four out
      of 59 guidelines met inclusion criteria and were included. They were published
      between 2005 and 2014. Three out of four guidelines reached a high level of
      quality, having at least five domain scores higher than 60%. Domain 1 (Scope and
      Purpose) achieved the highest result (total score = 86.8 +/- 3.7%). Domain 6
      (Editorial Independence) had the lowest score (total score = 54.7 +/- 12.5%).
      Interobserver agreement ranged from fair (0.230) to good (0.702). CONCLUSIONS:
      Overall, the quality of DXA guidelines is satisfactory when evaluated using the
      AGREE II instrument. The Editorial Independence domain was the most critical,
      thus deserving more attention when developing future guidelines. MAIN MESSAGES: *
      Three of four guidelines on DXA had a high quality level (>60%). * Scope/purpose
      had the highest score (86.8 +/- 3.7%). * Editorial Independence had the lowest
      score (54.7 +/- 12.5%). * Interobserver agreement ranged from fair (0.230) to
      good (0.702).

PMID- 28432575
TI  - Liver Transplantation: the Role of Metabolic Syndrome.
AB  - OPINION STATEMENT: The long-term survival in liver transplant recipients (LTRs)
      is currently at an historical high level stemming from improvement in
      perioperative care, infection control, and immunosuppression medications.
      However, compared to the general population, LTRs have decreased survival.
      Metabolic diseases like hypertension, dyslipidemia, type 2 diabetes, and obesity
      are key determinants of long-term mortality in LTRs. The incidence and prevalence
      of these metabolic comorbidities is considerably higher in LTRs and likely
      results from a combination of factors including exposure to chronic
      immunosuppression, weight gain, and recurrence of chronic liver disease after
      liver transplantation (LT). Although there is currently little guidance in
      managing these metabolic conditions post-LT, recommendations are often
      extrapolated from non-transplant cohorts. In the current review, we explore the
      relationship between metabolic syndrome and its comorbidities in LTRs.

PMID- 28432576
TI  - Clinical benefit of neoadjuvant chemoradiotherapy for the avoidance of
      pneumonectomy; assessment in 12 consecutive centrally located non-small cell lung
      cancers.
AB  - BACKGROUND: Considering that pneumonectomy itself is a disease, avoidance of
      pneumonectomy needs to be deliberated. Herein, we evaluated the role of
      neoadjuvant chemoradiotherapy for avoidance of pneumonectomy in patients with
      centrally located locally advanced non-small cell lung cancer. METHODS: Patients
      who underwent neoadjuvant chemoradiotherapy after being judged to require
      pneumonectomy by cancer board between 1997 and 2011 were retrospectively
      evaluated. RESULTS: Twelve patients, including 10 males and 2 females with median
      age 63.5 years, were referred. Clinical stage was IB (1 patient), IIB (2
      patients), IIIA (8 patients), and IIIB (1 patient). There were no disease
      progression after neoadjuvant chemoradiotherapy, and all patients underwent
      curative resection. For 8 patients, pneumonectomy was avoided, with 3
      bronchoplasties and 3 pulmonary arterial angioplasties. We had 4 pneumonectomies:
      three cases of metastatic enlarged lymph nodes invading either the carina or a
      more central portion of the pulmonary artery than the left A3 branch or vein
      which needs incision of the inner pericardium and 1 case with a tumor involving
      the upper lobe bronchus to the inferior lobe bronchus. There were no
      postoperative deaths and 1 case of bronchopleural fistula. The 5-year disease
      free and overall survival rates were 55.6 and 72.7% without stump or anastomotic
      recurrence. CONCLUSIONS: Neoadjuvant chemoradiotherapy for centrally located
      NSCLC appeared to be a useful treatment option for avoiding pneumonectomy without
      impairing curability and safety, especially in highly selected cases without
      invasion to carina or right-or-left main trunk of pulmonary artery or vein at
      pretreatment.

PMID- 28432577
TI  - Implicit Reasons for Disclosure of the Use of Complementary Health Approaches
      (CHA): a Consumer Commitment Perspective.
AB  - BACKGROUND: Disclosure of the use of complementary health approaches (CHA) is an
      important yet understudied health behavior with important implications for
      patient care. Yet research into disclosure of CHA has been atheoretical and
      neglected the role of health beliefs. PURPOSE: Using a consumer commitment model
      of CHA use as a guiding conceptual framework, the current study tests the
      hypotheses that perceived positive CHA outcomes (utilitarian values) and positive
      CHA beliefs (symbolic values) are associated with disclosure of CHA to
      conventional care providers in a nationally representative US sample. METHODS:
      From a sample of 33,594 with CHA use information from the 2012 National Health
      Interview Survey (NHIS), a subsample of 7348 who used CHA within the past 12
      months was analyzed. The 2012 NHIS is a cross-sectional survey of the non
      institutionalized US adult population, which includes the most recent nationally
      representative CHA use data. RESULTS: The 63.2% who disclosed CHA use were older,
      were less educated, and had visited a health care provider in the past year.
      Weighted logistic regression analyses controlling for demographic variables
      revealed that those who disclosed were more likely to report experiencing
      positive psychological (improved coping and well-being) and physical outcomes
      (better sleep, improved health) from CHA and hold positive CHA-related beliefs.
      CONCLUSIONS: CHA users who perceive physical and psychological benefits from CHA
      use and who hold positive attitudes towards CHA are more likely to disclose their
      CHA use. Findings support the relevance of a consumer commitment perspective for
      understanding CHA disclosure and suggest CHA disclosure as an important proactive
      health behavior that warrants further attention.

PMID- 28432578
TI  - A Randomized Controlled Trial of Rise, a Community-Based Culturally Congruent
      Adherence Intervention for Black Americans Living with HIV.
AB  - BACKGROUND: Evidence-based HIV treatment adherence interventions have typically
      shown medium-sized effects on adherence. Prior evidence-based HIV treatment
      adherence interventions have not been culturally adapted specifically for
      Black/African Americans, the population most affected by HIV disparities in the
      USA, who exhibit lower adherence than do members of other racial/ethnic groups.
      PURPOSE: We conducted a randomized controlled trial of Rise, a 6-month culturally
      congruent adherence counseling intervention for HIV-positive Black men and women.
      METHODS: Rise was delivered by a trained peer counselor who used a problem
      solving approach to address culturally congruent adherence barriers (e.g.,
      medical mistrust, HIV stigma) and assisted with linkage to supportive services. A
      total of 215 participants were randomized to the intervention group (n = 107) or
      a wait-list control group (n = 108). Adherence was assessed daily via electronic
      monitoring. RESULTS: In a repeated measures multivariate logistic regression
      model of dichotomous adherence (using a clinically significant cutoff of 85% of
      doses taken), adjusted for sociodemographic and medical covariates, adherence in
      the intervention group improved over time relative to the control group, (OR =
      1.30 per month (95% CI = 1.12-1.51), p < 0.001), representing a large cumulative
      effect after 6 months (OR = 4.76, Cohen's d = 0.86). CONCLUSIONS: Rise showed a
      larger effect on adherence than prior HIV adherence intervention studies. For
      greater effectiveness, interventions to improve adherence among Black people
      living with HIV may need to be customized to address culturally relevant barriers
      to adherence. ( ClinicalTrials.gov #NCT01350544).

PMID- 28432579
TI  - HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who
      Inject Drugs.
AB  - PURPOSE OF REVIEW: Highly effective, well-tolerated interferon-free direct-acting
      antivirals (DAA) have revolutionised hepatitis C virus (HCV) therapeutics, with
      the opportunity for broad treatment scale-up among marginalised or "high-risk"
      populations, including people who inject drugs (PWID) and people with HIV/HCV
      coinfection. RECENT FINDINGS: Concern that HCV reinfection may compromise HCV
      treatment outcomes is sometimes cited as a reason for not offering treatment to
      current and former PWID. However, the incidence of reinfection following
      interferon-based treatment for chronic HCV is low among PWID. Reinfection rates
      in HIV-positive men-who-have-sex-with-men (MSM) are varied, with high incidence
      reported in some cohorts. Mathematical modelling suggests that substantial
      reductions in HCV incidence and prevalence could be achieved with targeted DAA
      therapy among those at the highest risk of ongoing transmission. This review will
      summarise the recent literature on DAA efficacy in PWID and people with HIV/HCV
      coinfection, discuss the individual- and population-level impact of DAA treatment
      scale-up and reinfection, and highlight ongoing and future research questions in
      expanding HCV care and treatment to those populations at high risk of ongoing HCV
      transmission.

PMID- 28432580
TI  - Corneal melting in rheumatoid arthritis patients treated with a tectonic
      reinforcing corneolimbal graft: an interventional case series.
AB  - PURPOSE: Corneal melting with perforation is a severe ophthalmic complication of
      autoimmune disorders such as rheumatoid arthritis. It requires urgent medical
      management in order to maintain the integrity of the globe and preserve vision.
      Treating this complication by penetrating keratoplasty is problematic due to the
      high rate of recurrence of corneal melting as well as other complications. We
      describe the use of a tectonic fresh-tissue corneolimbal covering graft. METHODS:
      An interventional case series including three patients that presented to our
      tertiary center between 2000 and 2015 with corneal melting and perforation,
      secondary to rheumatoid arthritis. Emergency surgery included suturing of a 13.00
      to 13.50-mm full-thickness fresh-tissue corneolimbal covering graft to the
      patient's posterior limbal zone. RESULTS: The corneolimbal graft maintained the
      integrity of the cornea in all cases, by sealing the perforation and promoting
      the creation of a fibrovascular scar at the area of corneal melting. There were
      no complications, recurrences of host corneal melting, or perforation during the
      follow-up period. CONCLUSION: Fresh-tissue full-thickness corneolimbal grafts may
      be used to cover emergency corneal melting and perforations secondary to
      rheumatoid arthritis.

PMID- 28432582
TI  - Hand Foot and Mouth Disease Like Illness in Office Practice: Correspondence.

PMID- 28432581
TI  - Comparison of immediate versus deferred intravitreal Bevacizumab in macular
      oedema due to branch retinal vein occlusion: a pilot study.
AB  - PURPOSE: To compare visual and anatomical recovery of immediate versus deferred
      intravitreal Bevacizumab for the treatment of macular oedema secondary to branch
      retinal vein occlusion (BRVO). METHODS: In a pilot study, 40 treatment naive
      patients of branch retinal vein occlusion with macular oedema and vision 6/12 or
      less presenting within one month of onset were randomised into 2 groups (20 each)
      to receive either immediate intravitreal Bevacizumab or deferred (after 3 months
      of observation). Outcome in terms of visual recovery and decrease in central
      macular thickness on the Optical Coherence Tomography (OCT) from pre-treatment
      level was analysed at 6 and 12 months from starting of treatment and compared
      between the two groups. RESULTS: The mean visual gain in the two groups early and
      delayed intervention was 0.38 log MARs and 0.15 log MAR units, respectively, and
      the superior vision gain in the early intervention group was statistically
      significant (p < 0.001). The difference in visual improvement between the two
      groups persisted till 1 year of follow-up. The early intervention group required
      fewer injections (2.6 +/- 71 vs. 3.5 +/- 0.51), and rescue laser treatment (15
      vs. 25%) as compared to deferred group. Both groups showed significant decrease
      in central macular thickness (328 and 289 u, respectively) from baseline
      thickness, but the difference between the two groups was not statistically
      significant (p = 0.45). CONCLUSIONS: Both early as well as deferred injection of
      Bevacizumab in macular oedema due to BRVO resulted in reduction of macular oedema
      and visual gain but immediate injection were associated with significantly
      greater visual gain with lesser number of injections fewer rescue laser
      treatment.

PMID- 28432583
TI  - Can Long-Term Pharmacotherapy Prevent Relapses in Generalized Anxiety Disorder? A
      Systematic Review.
AB  - BACKGROUND AND OBJECTIVES: Generalized anxiety disorder (GAD) is a persistent
      anxiety disorder with a high rate of relapse. While several trials have
      demonstrated the efficacy of pharmacotherapy for GAD treatment, fewer studies
      have investigated its efficacy in preventing symptom relapse in long-term
      treatment. The aim of this study is to evaluate if long-term pharmacotherapy may
      prevent relapses in GAD patients. METHODS: This is a systematic review of the
      relapse prevention trials with GAD patients. RESULTS: Eight trials were included
      in this review with 5304 patients in total. All patients showed a higher risk of
      relapse if treatment was not maintained for at least 6 months after remission,
      with hazard ratios ranging from 0.12 to 0.58 and mostly moderate effect sizes
      (0.19-1.06). CONCLUSION: Long-term pharmacotherapy may prevent symptom relapse in
      GAD patients. As the relapse rate is very high, the data support the continuation
      of pharmacotherapy for as long as possible.

PMID- 28432584
TI  - Clinical features and long-term outcomes of pediatric spinal meningiomas.
AB  - Pediatric spinal meningiomas are very rare. Most studies on pediatric spinal
      meningiomas are case reports with literature reviews. This study presented a
      surgical series of 14 pediatric patients with histologically proven sporadic
      spinal meningiomas, including 5 WHO grade II tumors. In this series, there were 9
      male and 5 female patients with a mean age of 11.1 years. Seven tumors were
      located in the cervical spine, 5 in the thoracic spine, and 2 in the lumbar
      spine. Gross total resection (GTR) of the tumor with a well-demarcated dissection
      plane was achieved in 11 cases, subtotal resection was achieved in 2 cases, and
      partial resection was performed in 1 case. The symptoms were improved in 10 cases
      at the last follow-up and the current status of 2 patients worsened and 1 patient
      had no change compared to the preoperative presentation. One patient died of
      progressive tumor regrowth after partial resection and adjuvant radiotherapy. The
      postoperative follow-up magnetic resonance imaging showed tumor recurrence in one
      of the 11 GTR cases during the mean follow-up period of 72.5 months.
      Recurrence/regrowth of the residual tumors was observed in both the 2 STR cases.
      Although pediatric spinal meningiomas have a higher incidence of WHO grade II
      meningiomas, they are amenable to surgery if it is possible to achieve GTR. A
      good clinical outcome after GTR can be expected, even for WHO grade II
      meningiomas. Effect of adjuvant radiochemotherapy for controlling the tumors is
      still unclear and requires further investigation.

PMID- 28432585
TI  - Patterns of care and treatment outcomes in older adults with low grade glioma: a
      50-year experience.
AB  - The purpose of this study was to identify changes in presentation, treatment and
      outcomes of older patients with low-grade glioma (LGG) over the past 50 years. 94
      adults aged 55 or older upon diagnosis of a WHO grade II LGG at Mayo Clinic
      between 1960 and 2011 were included and grouped by those diagnosed before (group
      I: 1960-1989) and after (group II: 1990-2011) the routine use of post-operative
      MRI. Median follow-up was 11.4 years. Pathologic diagnoses included astrocytoma
      in 55%, mixed oligoastrocytoma in 18% and oligodendroglioma in 27%. Gross total
      resection (GTR) was achieved in 10%, radical subtotal resection (rSTR) in 6%,
      subtotal resection (STR) in 20% and biopsy only in 64%. Post-operative
      radiotherapy (PORT) was given in 77%. More patients in the modern era received
      GTR/rSTR (20 vs. 7%), though the difference was not statistically significant.
      Median progression-free survival (PFS) was 3.0 years, with 5- and 10-year PFS
      rates of 31 and 10%, respectively. Median, 5- and 10-year overall survival (OS)
      was 4.1 years, 43 and 17%, respectively. PFS and OS did not improve in the modern
      era. Factors negatively associated with PFS on multivariate analysis included
      astrocytoma histology, contrast enhancement and STR/biopsy. Factors associated
      with poor OS on multivariate analysis included astrocytoma histology, deep
      location, contrast enhancement and STR/biopsy. Despite reports of improving
      outcomes for younger patients treated in the modern era, outcomes have not
      significantly improved for older patients. Further efforts to improve outcomes
      based on molecular genotyping are needed to determine a rational strategy for
      treatment intensification.

PMID- 28432586
TI  - CDC20 with malignant progression and poor prognosis of astrocytoma revealed by
      analysis on gene expression.
AB  - The malignant transformation of astrocytoma may result from the accumulation of
      multiple genetic alterations. Current research shows that diffuse astrocytoma
      (AIIs, WHO grade II) is inherently predisposed to recur locally, and to
      spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and
      eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study
      was to identify and validate the important gene(s) associated with malignant
      progression and poor prognosis of astrocytoma. Average expression levels of 82
      samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through
      no-paired student test. Candidate genes were screened by DAVID and Kaplan-Meier
      survival analysis. Further, the significant candidate genes were validated
      through real-time PCR(qPCR), western blot and immunohistochemistry (IHC) in
      different grades of glioma. Finally, the association of target gene and clinical
      molecular characterization was analyzed by Chi-squared analysis. The cell
      division cycle protein 20(CDC20, p = 0.0129) and the polo-like kinase 1(PLK1, p =
      0.0046) were screened by statistical and Kaplan-Meier survival analysis. The
      expression levels of CDC20 and PLK1 rose significantly through real-time
      PCR(qPCR), western blot and IHC. A chi-squared analysis showed that patients with
      CDC20 high-expression differ from patients with CDC20 low-expression in terms of
      WHO classification (p < 0.0001), karnofsky performance score (KPS, p < 0.0001),
      isocitrate dehydrogenase mutation (IDH1, p < 0.0001), phosphatase and tensin
      homolog mutation (PTEN, p = 0.027) and epidermal growth factor receptor protein
      amplification (EGFR, p = 0.048). Moreover, the biological processes analyses
      indicate CDC20 might have an essential role in astrocyte cell proliferation. We
      demonstrated that the expression level of CDC20 increases significantly along
      with malignant progression and poor prognosis of astrocytoma.

PMID- 28432588
TI  - Patterns of care and outcomes of multi-agent versus single-agent chemotherapy as
      part of multimodal management of low grade glioma.
AB  - For high-risk low-grade gliomas (LGGs), adjuvant radiotherapy (RT) with
      procarbazine/lomustine/vincristine (PCV) chemotherapy increases overall survival
      (OS) over RT alone. However, in practice, temozolomide (TMZ) is often used
      instead of PCV. Using the National Cancer Data Base (NCDB), we provide the first
      investigation of practice patterns and outcomes of chemoradiotherapy with single
      agent chemotherapy (SAC, analogous to TMZ) or multi-agent chemotherapy (MAC,
      analogous to PCV) for LGG. Patients with high-risk Grade II LGGs were queried in
      the NCDB. Inclusion was limited to patients treated with definitive RT and
      chemotherapy. Patients were divided into cohorts receiving SAC or MAC. Kaplan
      Meier analysis compared overall survival (OS), and Cox proportional hazards
      models determined variables independently associated with OS. Of 1029 patients,
      989 (96.1%) received SAC, while 40 (3.9%) received MAC. Patients treated more
      recently (2010-2012) were less likely to receive MAC (p = 0.029). No differences
      in median OS were observed between patients treated with MAC and SAC (45.3 vs.
      59.2 months, p = 0.861). Independent predictors of worse OS included age >40,
      high Charlson-Deyo index, other governmental/unrecorded insurance status, biopsy
      only, astrocytoma histology, Western geographical region, and higher income.
      Substuting MAC with SAC had no impact on OS (p = 0.804). There is a significantly
      greater utilization of SAC compared to MAC in the US. There were no differences
      in OS between patients receiving SAC and MAC, nor did this factor impact OS on
      multivariate analysis, suggesting that the practice of substituting MAC with SAC
      for management of LGG may not adversely affect outcome.

PMID- 28432587
TI  - Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine
      consolidation for primary central nervous system lymphoma (PCNSL) in the elderly:
      a LOC network study.
AB  - Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based
      chemotherapy. However, responses in the elderly are short-lasting and outcome is
      poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe
      toxicities, alternative consolidation approaches need to be evaluated. In this
      multicenter study, we retrospectively analyzed consecutive patients with newly
      diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen
      consisted of three 28-day cycles of methotrexate (3.5 g/m2 D1, D15),
      procarbazine, vincristine, followed by three 28-day cycles of cytarabine
      consolidation (3 g/m2 D1-2). Addition of rituximab (375 mg/m2 D1) was optional.
      The results were compared with the historical MPV-A regimen. Ninety patients
      received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab.
      Median age was 68 and median KPS 60. 55% of patients achieved a complete
      response, 8% a partial response and 37% progressed. The median PFS was 10 months,
      the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of
      grade III-IV neutropenia and thrombopenia. The response rate was higher in
      patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was
      observed in terms of PFS or OS. When comparing the results to the historical MPV
      A, there was no difference in terms of response rate, PFS or OS, but a higher
      rate of hematotoxicity. This study suggests that extending cytarabine
      consolidation after methotrexate-based chemotherapy does not improve the MPV-A
      efficacy but increases toxicity in the elderly. The addition of rituximab may
      improve the response rate, but its impact on final outcome remains unclear.

PMID- 28432589
TI  - Expression and function of ABCG2 and XIAP in glioblastomas.
AB  - Despite multimodal treatment that includes surgery, radiation and chemotherapy,
      virtually all glioblastomas (GBM) recur, indicating that these interventions are
      insufficient to eradicate all malignant cells. To identify potential new
      therapeutic targets in GBMs, we examined the expression and function of proteins
      that are associated with therapy resistance and cancer cell survival. We measured
      the expression of eight such proteins in 50 GBM samples by immunohistochemistry
      and analyzed patient survival. We report that GBM patients with high expression
      of ABCG2 (also called BCRP) or XIAP at the protein level had worse survival than
      those with low expression. The adjusted hazard ratio for ABCG2 was 2.35 and for
      XIAP was 2.65. Since glioma stem cells (GSCs) have been shown to be more
      resistant than bulk tumor cells to anti-cancer therapies and to express high
      levels of these proteins, we also sought to determine if ABCG2 and XIAP have
      functional roles in GSCs. We used small molecule inhibitors to treat patient
      derived GBM tumorspheres in vitro and observed that inhibitors of ABCG2, Ko143
      and fumitremorgin, significantly reduced self-renewal. These results suggest that
      ABCG2 and XIAP proteins may be useful indicators of patient survival and that
      inhibition of ABCG2 may be a promising therapeutic strategy in GBMs.

PMID- 28432590
TI  - Pathological analysis of the surgical margins of resected glioblastomas excised
      using photodynamic visualization with both 5-aminolevulinic acid and fluorescein
      sodium.
AB  - During glioma resection, 5-aminolevulinic acid (5-ALA) and fluorescein sodium (Fl
      Na) are used for photodynamic tumor visualization. The objective of this study
      was to evaluate the pathological findings of the boundary zone between the tumor
      and adjacent normal brain in glioblastoma patients undergoing simultaneous double
      staining with 5-ALA and Fl-Na during surgery. Eight patients received 5-ALA (20
      mg/kg orally) before the induction of general anesthesia, and Fl-Na (20 mg/kg)
      was administered intravenously before the dural incision was performed. The tumor
      bulk was removed under the guidance of Fl-Na staining alone using conventional
      white light. Subsequently, residual tumor was removed under the guidance of both
      fluorescent agents within functionally safe limits until both were visibly
      undetectable. Twenty specimens exhibiting different staining intensities of both
      agents were obtained. The vessel index (VI) was calculated from CD31
      immunohistochemistry (IHC) samples. Boundary zone tumor cells were detected by
      IHC for olig2, and were expressed as the olig2 index (OLI). The VI was
      significantly higher in Fl-Na-positive areas than in Fl-Na-negative areas (p =
      0.0005). In contrast, the OLI was significantly higher in 5-ALA-positive areas
      than in 5-ALA-negative areas (p = 0.0149). 5-ALA-positive/Fl-Na negative areas
      were observed in 7 patients. These findings indicate that Fl-Na accumulates in
      areas with a disrupted blood-brain barrier, and that 5-ALA fluorescence is
      dependent on tumor cell protoporphyrin IX metabolism. In conclusion, 5-ALA was
      better for detecting tumor cells in the boundary zone than was Fl-Na. Of note,
      tumor cells existed outside the fluorescence-stained boundaries of both agents.

PMID- 28432591
TI  - Prior beliefs influence symmetrical or asymmetrical generalizations in human
      causal learning.
AB  - The generalization decrement between element A and compound AX has shown both
      symmetrical (Thorwart & Lachnit, 2009) and asymmetrical (Glautier, 2004) patterns
      in human contingency learning. In a series of experiments we examined the
      hypothesis that prior beliefs about the relationship between a distinctive
      element X and an outcome are important for determining the different
      generalization patterns. Participants learned which given enterobacteria caused a
      negative or a positive effect on gastrointestinal conditions. Subsequently, they
      were asked to evaluate learned cues and novel cues in which distinctive elements
      were added to or removed from the enterobacteria. The results generally
      demonstrated that relatedness between the elements and outcomes, such as negative
      features combined with a negative outcome or positive features combined with a
      positive outcome, resulted in asymmetrical generalization patterns. By contrast,
      unrelated combinations, such as positive features and a negative outcome,
      produced symmetrical patterns of generalization. Configural and elemental models
      of stimulus generalization are discussed.

PMID- 28432592
TI  - Perceptual learning with tactile stimuli in rodents: Shaping the somatosensory
      system.
AB  - The animal kingdom contains species with a wide variety of sensory systems that
      have been selected to function in different environmental niches, but that are
      also subject to modification by experience during an organism's lifetime. The
      modification of such systems by experience is often called perceptual learning.
      In rodents, the classic example of perceptual learning is the observation that
      simple preexposure to two visual stimuli facilitates a subsequent (reinforced)
      discrimination between them. However, until recently very little behavioral
      research had investigated perceptual learning with tactile stimuli in rodents, in
      marked contrast to the wealth of information about plasticity in the rodent
      somatosensory system. Here we present a selective review of behavioral analyses
      of perceptual learning with tactile stimuli, alongside evidence concerning the
      potential bases of such effects within the somatosensory system.

PMID- 28432593
TI  - Talking About Breast Cancer: Which Symptoms and Treatment Side Effects are
      Important to Patients with Advanced Disease?
AB  - BACKGROUND: Patients' experience of symptoms and associated treatment is an
      increasingly important consideration in both regulatory and health technology
      assessments, and can inform treatment decisions. OBJECTIVE: This study aimed to
      gain insight directly from patients with advanced breast cancer about which
      symptoms and treatment side effects are important to them. METHODS: Women with
      locally advanced or metastatic breast cancer were interviewed individually by
      trained interviewers, using a semi-structured interview guide. Verbatim
      transcripts were analyzed qualitatively, including whether symptoms were
      mentioned spontaneously (indicating their importance to patients) or only when
      questioned directly. RESULTS: Sixteen women (aged 38-74 years) participated. The
      most commonly reported symptom aspects were: pain (16/16 [all reported
      spontaneously]); feeling tired/fatigued (15/16 [12 spontaneously]); changes in
      weight (15/16 [2 spontaneously]); hair loss (15/16 [5 spontaneously]); changes in
      appetite (11/16 [8 spontaneously]); nausea (9/16 [all spontaneously]). Pain was
      attributed mostly to the disease or to its treatment. Tiredness, changes in
      weight/appetite, and hair loss were attributed mostly to the treatment. All women
      (14 spontaneously) reported that the cancer affected their emotional well-being
      and their ability to perform daily activities. CONCLUSIONS: Further qualitative
      research is needed to understand how patients distinguish cancer-related symptoms
      from treatment-related side effects, to gain insight into which patient
      experiences should be measured and how best to measure them.

PMID- 28432594
TI  - MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells.
AB  - PURPOSE OF REVIEW: Multiple myeloma remains an incurable disease, largely due to
      the tumor-supportive role of the bone marrow microenvironment. Bone marrow
      adipose tissue (BMAT) is one component of the fertile microenvironment which is
      believed to contribute to myeloma progression and drug resistance, as well as
      participate in a vicious cycle of osteolysis and tumor growth. RECENT FINDINGS:
      MicroRNAs (miRNAs) have recently emerged as instrumental regulators of cellular
      processes that enable the development and dissemination of cancer. This review
      highlights the intersection between two emerging research fields and pursues the
      scientific and clinical implications of miRNA transfer between BMAT and myeloma
      cells. This review provides a concise and provocative summary of the evidence to
      support exosome-mediated transfer of tumor-supportive miRNAs. The work may prompt
      researchers to better elucidate the mechanisms by which this novel means of
      genetic communication between tumor cells and their environment could someday
      yield targeted therapeutics.

PMID- 28432595
TI  - What Animal Models Have Taught Us About the Safety and Efficacy of
      Bisphosphonates in Chronic Kidney Disease.
AB  - PURPOSE OF REVIEW: Bisphosphonates (BPs) have long been the gold-standard anti
      remodeling treatment for numerous metabolic bone diseases. Since these drugs are
      excreted unmetabolized through the kidney, they are not recommended for
      individuals with compromised kidney function due to concerns of kidney and bone
      toxicity. The goal of this paper is to summarize the preclinical BP work in
      models of kidney disease with particular focus on the bone, kidney, and
      vasculature. RECENT FINDINGS: Summative data exists showing positive effects on
      bone and vascular calcifications with minimal evidence for bone or kidney
      toxicity in animal models. Preclinical data suggest it may be worthwhile to take
      a step back and reconsider the use of bisphosphonates to lessen skeletal/vascular
      complications associated with compromised kidney function.

PMID- 28432596
TI  - Exploiting the WNT Signaling Pathway for Clinical Purposes.
AB  - PURPOSE OF REVIEW: The goal of this paper is to evaluate critically the
      literature published over the past 3 years regarding the Wnt signaling pathway.
      The Wnt pathway was found to be involved in bone biology in 2001-2002 with the
      discovery of a (G171V) mutation in the lipoprotein receptor-related protein 5
      (LRP5) that resulted in high bone mass and another mutation that completely
      inactivated Lrp5 function and resulted in osteoporosis pseudoglioma syndrome
      (OPPG). The molecular biology has been complex, and very interesting. It has
      provided many opportunities for exploitation to develop new clinical treatments,
      particularly for osteoporosis. More clinical possibilities include: treatments
      for fracture healing, corticosteroid osteoporosis, osteogenesis imperfecta, and
      others. In addition, we wish to provide historical information coming from
      distant publications (~350 years ago) regarding bone biology that have been
      confirmed by study of Wnt signaling. RECENT FINDINGS: A recent finding is the
      development of an antibody to sclerostin that is under study as a treatment for
      osteoporosis. Development of treatments for other forms of osteoporosis, such as
      corticosteroid osteoporosis, is also underway. The full range of the applications
      of the work is not yet been achieved.

PMID- 28432598
TI  - Animal Posters.

PMID- 28432597
TI  - T Regulatory Cells in Bone Remodelling.
AB  - PURPOSE OF THE REVIEW: In this review, we present the role of regulatory T (Treg)
      cells in bone remodelling and bone-related disease such as osteoporosis or
      inflammatory bone loss. We also discuss the cellular and molecular mechanism how
      Treg cells regulate osteoclastogenesis. RECENT FINDINGS: Treg cells could
      regulate osteoclastogenesis by secreting TGF-beta and IL-10 as well as IL-4
      cytokines. Moreover, Treg cells can additionally regulate osteoclast
      differentiation, in a cell-to-cell contact via the cytotoxic T lymphocyte antigen
      (CTLA-4). The latter induces the apoptosis of osteoclasts dependent on CD80/86 in
      vitro and in vivo. Treg cells mediate immunosuppressive function that controls
      undesired immune reactions, such as autoimmunity. Recently, Treg cells have been
      shown to influence non-immunological processes, such as bone homeostasis.
      Accumulated evidences have demonstrated that Treg cells can suppress osteoclast
      differentiation in vitro and in vivo.

PMID- 28432599
TI  - The beneficial effect of repaglinide on in vitro maturation and development
      ability of immature mouse oocytes.
AB  - Repaglinide is a hypoglycemic drug, causing depolarization of the cell membrane,
      opening the voltage-gated calcium channels, and then increasing intracellular
      calcium in the pancreatic B cells by inhibition of the K-ATP-sensitive channels.
      Oocyte in vitro maturation (IVM) is influenced by different factors such as
      calcium signaling. In this study, we examined the effects of repaglinide on in
      vitro maturation and fertilization ability of mouse oocyte. Immature oocytes were
      isolated from female Naval Medical Research Institute mice which are 6-8 wk old
      mechanically and then cultured in 30 MUl droplets of T6 medium with different
      concentrations of repaglinide. The control group did not receive repaglinide
      (R0). Treatment groups received different concentrations (5, 10, and 100 nM and 1
      and 10 MUM) of repaglinide (R1, R2, R3, R4, and R5, respectively). Oocyte in
      vitro maturation rate was assessed after 24 h. In vitro fertilization was
      performed using metaphase II oocytes obtained from R0 and R4 treatments. Embryo
      cleavage rate was calculated at 48 h post-IVF. Chi-square test was used for
      evaluating difference between control and treatment groups (p < 0.05). Oocyte
      maturation rate after 24 h in treatment groups R2, R3, R4, and R5 was
      significantly higher than that in the control (p < 0.05). Supplementation of
      medium with 1 MUM of repaglinide (R4) during IVM significantly improved outcome
      of embryo cleavage rate than control at 48 h post-IVF (p < 0.05). In conclusion,
      repaglinide can be considered as an effective agent for in vitro oocyte
      maturation and embryo cleavage.

PMID- 28432600
TI  - Potentially Inappropriate Antihypertensive Prescriptions to Elderly Patients:
      Results of a Prospective, Observational Study.
AB  - INTRODUCTION: Previous studies of antihypertensive treatment of older patients
      have focused on blood pressure control, cardiovascular risk or adherence, whereas
      data on inappropriate antihypertensive prescriptions to older patients are
      scarce. OBJECTIVES: The aim of the study was to assess inappropriate
      antihypertensive prescriptions to older patients. METHODS: An observational,
      prospective multicentric study was conducted to assess potentially inappropriate
      prescription of antihypertensive drugs, in patients aged 75 years and older with
      arterial hypertension (HTN), in the month prior to hospital admission, using four
      instruments: Beers, Screening Tool of Older Person's Prescriptions (STOPP),
      Screening Tool to Alert Doctors to the Right Treatment (START) and Assessing Care
      of Vulnerable Elders 3 (ACOVE-3). Primary care and hospital electronic records
      were reviewed for HTN diagnoses, antihypertensive treatment and blood pressure
      readings. RESULTS: Of 672 patients, 532 (median age 85 years, 56% female) had
      HTN. 21.6% received antihypertensive monotherapy, 4.7% received no hypertensive
      treatment, and the remainder received a combination of antihypertensive
      therapies. The most frequently prescribed antihypertensive drugs were diuretics
      (53.5%), angiotensin-converting enzyme inhibitors (ACEIs) (41%), calcium
      antagonists (32.2%), angiotensin receptor blockers (29.7%) and beta-blockers
      (29.7%). Potentially inappropriate prescription was observed in 51.3% of patients
      (27.8% overprescription and 35% underprescription). The most frequent
      inappropriately prescribed drugs were calcium antagonists (overprescribed), ACEIs
      and beta-blockers (underprescribed). ACEI and beta-blocker underprescriptions
      were independently associated with heart failure admissions [beta-blockers odds
      ratio (OR) 0.53, 95% confidence interval (CI) 0.39-0.71, p < 0.001; ACEIs OR
      0.50, 95% CI 0.36-0.70, p < 0.001]. CONCLUSION: Potentially inappropriate
      prescription was detected in more than half of patients receiving
      antihypertensive treatment. Underprescription was more frequent than
      overprescription. ACEIs and beta-blockers were frequently underprescribed and
      were associated with heart failure admissions.

PMID- 28432602
TI  - Sphenopalatine Ganglion Block in the Management of Chronic Headaches.
AB  - PURPOSE OF REVIEW: Sphenopalatine ganglion (SPG) block has been used by
      clinicians in the treatment of a variety of headache disorders, facial pain
      syndromes, and other facial neuralgias. The sensory and autonomic fibers that
      travel through the SPG provided the scientific rationale for symptoms associated
      with these head and neck syndromes. Yet, despite the elucidation of this
      pathogenic target, the optimal method to block its pain-producing properties has
      not been determined. Clinicians have developed various invasive and non-invasive
      techniques, each of which has shown variable rates of success. We examined the
      available studies of sphenopalatine ganglion blockade and its efficacy in the
      treatment of cluster headaches, migraines, and other trigeminal autonomic
      cephalalgias. RECENT FINDINGS: Studies have demonstrated that SPG blockade and
      neurostimulation can provide pain relief in patients with cluster headaches,
      migraines, and other trigeminal autonomic cephalalgias. Patients with these
      conditions showed varying levels and duration of pain relief from SPG blockade.
      The efficacy of SPG blockade could be related to the different techniques
      targeting the SPG and choice of therapeutic agents. Based on current studies, SPG
      blockade is a safe and effective treatment for chronic headaches such as cluster
      headaches, migraines, and other trigeminal autonomic cephalalgias. Future studies
      are warranted to define the optimal image-guided technique and choice of
      pharmacologic agents for SPG blockade as an effective treatment for chronic
      headaches related to activation of the sphenopalatine ganglion.

PMID- 28432601
TI  - Neuropathic Pain: Central vs. Peripheral Mechanisms.
AB  - PURPOSE OF REVIEW: Our goal is to examine the processes-both central and
      peripheral-that underlie the development of peripherally-induced neuropathic pain
      (pNP) and to highlight recent evidence for mechanisms contributing to its
      maintenance. While many pNP conditions are initiated by damage to the peripheral
      nervous system (PNS), their persistence appears to rely on maladaptive processes
      within the central nervous system (CNS). The potential existence of an autonomous
      pain-generating mechanism in the CNS creates significant implications for the
      development of new neuropathic pain treatments; thus, work towards its resolution
      is crucial. Here, we seek to identify evidence for PNS and CNS independently
      generating neuropathic pain signals. RECENT FINDINGS: Recent preclinical studies
      in pNP support and provide key details concerning the role of multiple mechanisms
      leading to fiber hyperexcitability and sustained electrical discharge to the CNS.
      In studies regarding central mechanisms, new preclinical evidence includes the
      mapping of novel inhibitory circuitry and identification of the molecular basis
      of microglia-neuron crosstalk. Recent clinical evidence demonstrates the
      essential role of peripheral mechanisms, mostly via studies that block the
      initially damaged peripheral circuitry. Clinical central mechanism studies use
      imaging to identify potentially self-sustaining infra-slow CNS oscillatory
      activity that may be unique to pNP patients. While new preclinical evidence
      supports and expands upon the key role of central mechanisms in neuropathic pain,
      clinical evidence for an autonomous central mechanism remains relatively limited.
      Recent findings from both preclinical and clinical studies recapitulate the
      critical contribution of peripheral input to maintenance of neuropathic pain.
      Further clinical investigations on the possibility of standalone central
      contributions to pNP may be assisted by a reconsideration of the agreed terms or
      criteria for diagnosing the presence of central sensitization in humans.

PMID- 28432603
TI  - Immunoprophylaxis of multi-antigen peptide (MAP) vaccine for human lymphatic
      filariasis.
AB  - Human lymphatic filariasis, the parasitic disease caused by the filarial
      nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori, is ranked as
      the second most complex clinical condition leading to permanent and long-term
      disability. The multiple antigen peptide (MAP) approach is an effective method to
      chemically synthesize and deliver multiple T and B cell epitopes as the
      constituents of a single immunogen. Here, we report on the design, chemical
      synthesis, and immunoprophylaxis of three epitopes that have been identified from
      promising vaccine candidates reported in our previous studies, constructed as MAP
      on an inert lysine core for human lymphatic filariasis in Jird model. Two
      epitopes from Thioredoxin and one epitope from Transglutaminase were constructed
      as MAP in an inert lysine core. The immunoprophylaxis of the synthetic vaccine
      construct studied in Jird models showed protective antibody (1 in 64,000 titer)
      and cellular immune response. Thioredoxin-Transglutaminase MAP (TT MAP) conferred
      a significantly high protection of 63.04% compared to control (8.5%). Multi
      antigen peptide vaccine is one best approach to provide immunity against multiple
      antigens delivered by the complex filarial parasite.

PMID- 28432604
TI  - Phosphate imbalance in patients with heart failure.
AB  - Patients with heart failure often exhibit electrolyte abnormalities, such as
      hyponatremia or hypokalemia/hyperkalemia. Although not as common as the other
      electrolyte disturbances observed in patients with heart failure, phosphate
      imbalance is also of high importance in this population. The aim of this review
      is to present the mechanisms of low or high phosphate serum levels in patients
      with heart failure and its role in the pathogenesis and progression of heart
      dysfunction. Hypophosphatemia in patients with heart failure may be the result of
      co-existing electrolyte and acid-base abnormalities, pharmacological treatments,
      decreased intestinal absorption or secondary to sympathetic nervous system
      activation and co-morbidities, such as diabetes mellitus or heavy alcohol
      consumption. Hypophosphatemia can affect multiple organ systems including the
      cardiovascular system. Depletion of phosphate can lead to ventricular arrhythmias
      and elimination of ATP synthesis, resulting in reversible myocardial dysfunction.
      Hyperphosphatemia, observed mainly in patients with chronic kidney failure, is
      also associated with cardiac hypertrophy, which may worsen cardiac contractility
      and heart failure. Studies have also shown an association of high-normal serum
      phosphate levels with vascular and valvular calcification. Therefore, serum
      phosphate imbalances may exhibit a causal role in the pathogenesis and
      progression of heart failure.

PMID- 28432606
TI  - Neuromuscular electrostimulation: a new therapeutic option to improve radio
      cephalic arteriovenous fistula maturation in end-stage chronic kidney disease
      patients.
AB  - BACKGROUND: Radio-cephalic arteriovenous fistula (RCAVF) is the gold standard
      vascular access for end-stage chronic kidney disease patients. Exercises after
      arteriovenous fistula (AVF) creation improve maturation. No articles are
      published regarding neuromuscular electrostimulation (NMES) in AVF maturation.
      OBJECTIVES: To assess the usefulness of a NMES programme on RCAVF maturation
      process. METHODS: An 8-week single-centre prospective study. Two groups were
      established: control group (CG): underwent usual RCAVF forearm exercises and
      electrostimulation group (ESG): underwent RCAVF NMES programme. Handgrip (HG)
      measurement, preoperative Doppler ultrasonography (DUS) parameters, clinical and
      DUS maturation as well as surgical complications were assessed. RESULTS: Thirty
      six patients (54% men). Mean age 67.9 +/- 14.3 years; 12 ESG and 24 CG.
      Demographic data, comorbidities, medical treatment, HG and DUS measurement at
      baseline were similar. HG increased in both groups at the end of the study (CG
      24.5 +/- 9.5 vs. 26.1 +/- 10.1 kg, p 0.048; ESG 25.8 +/- 10.3 vs. 26.3 +/- 11.6
      kg, p 0.644). RCAVF forearm vein diameter (CG 3.1 +/- 0.7 vs. 5.7 +/- 1.1 mm; ESG
      2.9 +/- 0.8 vs. 6.1 +/- 1.7 mm) and humeral artery blood flow rate (CG 110.5 +/-
      20.7 vs. 1053.4 +/- 510.7 ml/min; ESG 118.2 +/- 31.6 vs. 954.1 +/- 542.2 ml/min)
      statistically increased for both groups. A significant increase in clinical
      maturation in ESG (62.5 vs. 91.7%, p 0.046) at 8 weeks was observed. Four
      patients in each group developed juxta-anastomotic stenosis and were surgically
      repaired. No adverse NMES effects were registered. CONCLUSIONS: NMES of forearm
      muscles is a safe and effective technique to improve RCAVF maturation and
      constitutes a novel alternative to forearm isometrics exercises. Nevertheless,
      further studies are required to confirm the potential effect of NMES in the
      vascular access maturation process.

PMID- 28432607
TI  - Impact of the medical specialty on knowledge regarding multidrug-resistant
      organisms and strategies toward antimicrobial stewardship.
AB  - PURPOSE: Evidence is scarce on subject-specific knowledge of multidrug-resistant
      organisms and rational use of antibiotics. We aimed at evaluating attitude,
      perception, and knowledge about multidrug-resistant organisms (MDRO) and
      antibiotic prescribing among urologists versus other medical specialties.
      METHODS: Within the MR2-study (Multiinstitutional Reconnaissance of practice with
      MultiResistant bacteria), a questionnaire was conducted targeting general
      surgeons, internists, gynecologists, and urologists in 18 German hospitals. The
      influence of medical specialty on predetermined endpoints was assessed by
      multivariable logistic regression models. RESULTS: With 456 evaluable
      questionnaires, the response rate was 43% (456/1061). Within seven workdays prior
      to survey, urologists prescribed antibiotics to >5 patients more often than non
      urologists (50.7 vs. 24.3%; p < 0.001). Urologists were more confident regarding
      dosage, frequency, and duration of antibiotic treatment (p = 0.038) as well as in
      interpreting antibiograms (p < 0.001). Both urologists and non-urologists had
      poor knowledge about antibiotic stewardship. Urologists were more confident
      regarding local resistance patterns (p < 0.001). However, local rates of
      ciprofloxacin-resistant E. coli strains were correctly categorized by only 36.3
      and 31.2% of urologists and non-urologists, respectively (p = 0.168). Compared to
      non-urologists, urologists more often acknowledged the use of broad-spectrum
      antibiotic agents as a problem, potentially resulting in increased resistance
      pattern (p = 0.036). Conversely, 31.5 and 30.7% of urologists and non-urologists
      (p = 0.424), respectively, would prescribe broad-spectrum antibiotics to a female
      patient with an uncomplicated urinary tract infection. Urologists did not attend
      more training courses regarding multidrug-resistance or antibiotic prescribing
      and did not perceive a better quality of discharge letters regarding MDRO.
      CONCLUSIONS: There is substantial need for advanced training regarding MDRO and
      antibiotic stewardship, regardless of medical specialty.

PMID- 28432605
TI  - Cardiac magnetic resonance imaging in heart failure: where the alphabet begins!
AB  - Cardiac Magnetic Resonance Imaging has become a cornerstone in the evaluation of
      heart failure. It provides a comprehensive evaluation by answering all the
      pertinent clinical questions across the full pathological spectrum of heart
      failure. Nowadays, CMR is considered the gold standard in evaluation of
      ventricular volumes, wall motion and systolic function. Through its unique
      ability of tissue characterization, it provides incremental diagnostic and
      prognostic information and thus has emerged as a comprehensive imaging modality
      in heart failure. This review outlines the role of main conventional CMR
      sequences in the evaluation of heart failure and their impact in the management
      and prognosis.

PMID- 28432608
TI  - FPGASW: Accelerating Large-Scale Smith-Waterman Sequence Alignment Application
      with Backtracking on FPGA Linear Systolic Array.
AB  - The Smith-Waterman (SW) algorithm based on dynamic programming is a well-known
      classical method for high precision sequence matching and has become the gold
      standard to evaluate sequence alignment software. In this paper, we propose fine
      grained parallelized SW algorithms using affine gap penalty and implement a
      parallel computing structures to accelerating the SW with backtracking on FPGA
      platform. We analysis the dynamic parallel computing features of anti-diagonal
      elements and storage expansion problem resulting from backtracking stage, and
      propose a series of optimization strategies to eliminate data dependency, reduce
      storage requirements, and overlap memory access latency. Our implementation is
      capable of supporting multi-type, large-scale biological sequence alignment
      applications. We obtain a speedup between 3.6 and 25.2 over the typical SW
      algorithm running on a general-purpose computer configured with an Intel Core i5
      3.2 GHz CPU. Moreover, our work is superior to other FPGA implementations in both
      array size and clock frequency, and the experiment results show that it can get a
      performance closed to that of the latest GPU implementation, but the power
      consumption is only about 26% of that of the GPU platforms.

PMID- 28432609
TI  - Mesenteric Cystic Teratoma Masquerading as Acute Abdomen.

PMID- 28432610
TI  - Left Versus Right: Does Location Matter for Refractory Metastatic Colorectal
      Cancer Patients in Phase 1 Clinical Trials?
AB  - PURPOSE: Location of the primary tumor is prognostic and predictive of efficacy
      with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal
      cancer (mCRC) patients. However, little is known regarding the effect of location
      on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF
      I and EGFR-I in regards to location of the primary tumor in patients with
      refractory mCRC enrolled in early phase studies. METHODS: A historical cohort
      analysis of mCRC patients, including 44 phase I trials our institution, from
      March 2004 to September 2012. Median Progression free survival (mPFS) and overall
      survival (mOS) were estimated from Kaplan-Meier curves and groups were
      statistically compared with the log-rank test. RESULTS: One hundred thirty-nine
      patients with a median age 59 (33-81). 73.9% received 3+ lines of therapy. All
      KRAS wild-type patients had received prior EGFR-I. LOCATION: right 20.9%, left
      61.9%, and transverse 4.3%. For survival analysis, transverse CRC were included
      with right. Of the 112 patients, mOS was left (N = 80) 6.6 months versus right (N
      = 32) 5.9 months, P = 0.18. mPFS was left (n = 86) 2.0 months versus right (N =
      35) 2.0 months, P = 0.76. In subgroup analysis, survival was significant for KRAS
      wild-type patients with left-sided mCRC had mOS of 6.2 months with other agents
      versus 9.4 months with EGFR-I (P = 0.03). CONCLUSIONS: In phase 1 clinical
      trials, although location alone was not prognostic in heavily pretreated
      patients, left-sided mCRC had improved survival with EGFR-I. Despite progression
      on EGFR-I, left-sided KRAS wild mCRC patients should be considered for phase 1
      studies of agents targeting growth factor pathways.

PMID- 28432611
TI  - Comparison of human erythrocyte purine nucleotide metabolism and blood purine and
      pyrimidine degradation product concentrations before and after acute exercise in
      trained and sedentary subjects.
AB  - This study aimed at evaluating the concentration of erythrocyte purine
      nucleotides (ATP, ADP, AMP, IMP) in trained and sedentary subjects before and
      after maximal physical exercise together with measuring the activity of purine
      metabolism enzymes as well as the concentration of purine (hypoxanthine,
      xanthine, uric acid) and pyrimidine (uridine) degradation products in blood. The
      study included 15 male elite rowers [mean age 24.3 +/- 2.56 years; maximal oxygen
      uptake (VO2max) 52.8 +/- 4.54 mL/kg/min; endurance and strength training 8.2 +/-
      0.33 h per week for 6.4 +/- 2.52 years] and 15 sedentary control subjects (mean
      age 23.1 +/- 3.41 years; VO2max 43.2 +/- 5.20 mL/kg/min). Progressive incremental
      exercise testing until refusal to continue exercising was conducted on a bicycle
      ergometer. The concentrations of ATP, ADP, AMP, IMP and the activities of adenine
      phosphoribosyltransferase (APRT), hypoxanthine-guanine phosphoribosyltransferase
      (HGPRT) and phosphoribosyl pyrophosphate synthetase (PRPP-S) were determined in
      erythrocytes. The concentrations of hypoxanthine, xanthine, uric acid and uridine
      were determined in the whole blood before exercise, after exercise, and 30 min
      after exercise testing. The study demonstrated a significantly higher
      concentration of ATP in the erythrocytes of trained subjects which, in part, may
      be explained by higher metabolic activity on the purine re-synthesis pathway
      (significantly higher PRPP-S, APRT and HGPRT activities). The ATP concentration,
      just as the ATP/ADP ratio, as well as an exercise-induced increase in this ratio,
      correlates with the VO2max level in these subjects which allows them to be
      considered as the important factors characterising physical capacity and exercise
      tolerance. Maximal physical exercise in the group of trained subjects results not
      only in a lower post-exercise increase in the concentration of hypoxanthine,
      xanthine and uric acid but also in that of uridine. This indicates the
      possibility of performing high-intensity work with a lower loss of not only
      purine but also pyrimidine.

PMID- 28432612
TI  - Evaluation of the analgesia nociception index (ANI) in healthy awake volunteers.
AB  - BACKGROUND: Analgesia might be evaluated with simple changes in vital signs, a
      non-specific and non-sensitive method. Heart rate variability (HRV) correlates
      with autonomous nervous system activity and can be used to evaluate painful
      stimuli. Heart rate variability is then transformed into a numeric scale called
      the analgesia nociception index (ANI), where higher values represent predominant
      parasympathetic tone, thus low nociception. Under general anesthesia, the ANI
      decreases following painful stimuli and increases after administration of
      analgesia, but significant interindividual variability is present. The goal of
      the present study was to evaluate the ANI as a pain index in healthy awake
      volunteers. METHODS: Following research ethics board approval, participants were
      positioned supine in a calm operating room. The participants' vital signs and ANI
      were monitored. After evaluation of all parameters without any stimulation, 23
      volunteers received a 2 Hz electrical stimulus at the wrist with increasing
      current intensity from 0-30 mA (5 mA increments). The current was kept constant
      for three minutes at each level, and the volunteers rated their pain on a numeric
      rating scale (NRS) every minute. The Pearson correlation coefficient and linear
      regression were used to analyze the relationship between the ANI and the NRS
      score. The ANI absolute values and the variations from baseline were both
      analyzed. RESULTS: There was a very weak negative correlation between the NRS
      score and ANImean (Pearson, -0.089; 95% confidence interval [CI], -0.192 to 
      0.014; P = 0.045) and between the NRS score and ?ANImean (Pearson, -0.174; 95%
      CI, -0.272 to -0.072; P < 0.001; regression slope, -0.586; 95% CI, -0.930 to 
      0.243; P < 0.001). Heart rate, blood pressure, and respiratory rate did not vary
      significantly throughout the study. CONCLUSIONS: These findings provide little
      evidence to support use of the ANI in awake subjects or in awake patients such as
      those in the emergency room or in the intensive care unit. Nevertheless, based on
      an important difference between the expected correlation and the real correlation
      between the ANI and the NRS scores found in our results, the present study might
      be underpowered. Studies with a larger sample size would be required to enable
      firm conclusions about the clinical utility of the ANI in this population of
      awake volunteers as well as in awake patients. This study was registered with
      ClinicalTrials.gov (NCT02589093).

PMID- 28432613
TI  - Pediatric tonsillectomy is a resource-intensive procedure: a study of Canadian
      health administrative data.
AB  - BACKGROUND: The majority of pediatric surgeries are performed in a day surgery
      setting. The rate of adverse postoperative outcomes and the factors that
      influence them are poorly described in the Canadian setting. Concerns about the
      safety of adenotonsillectomy (AT) have been raised. The objective of this Ontario
      based study was to determine the rates and risks of hospital readmission,
      emergency department (ED) visits, or deaths within 30 days following common
      pediatric surgeries, with an emphasis on AT. METHODS: Inpatient and day surgery
      children who were < 18 yr of age and undergoing one of the ten most common
      surgeries in Ontario from 2002-2013 were identified by linking four provincial
      health administrative databases. Risk of each outcome was determined separately
      for all surgeries. Cox regression was used to measure the association of
      demographics, clinical factors, Ontario drug benefit (ODB) status, and prescribed
      opioids with adverse outcomes. RESULTS: Among 364,629 children, AT accounted for
      30.5% of all surgeries. The AT patient rates of readmission and ED visits
      compared with the full study cohort were 2.7% vs 1.5% and 12.4% vs 9.2%,
      respectively. The study cohort postoperative death rate was 0.27 per 10,000
      children (95% confidence interval [CI], 0.18 to 0.39). For the study cohort, an
      increased risk of readmission was associated with previous urgent admission
      (hazard ratio [HR], 2.15; 95% CI, 1.75 to 2.63), length-of-stay >= four days (HR,
      2.04; 95% CI, 1.57 to 2.65), Charlson comorbidity score >= 1 (HR, 1.61; 95% CI,
      1.17 to 2.22), and age >= 14 yr (HR, 1.15; 95% CI, 1.02 to 1.19) or <= 3 yr (HR,
      1.16; 95% CI, 1.15 to 1.17). Similar factors were associated with an increased
      risk of ED visits. Patients covered by ODB (11.8%), particularly those prescribed
      opioids, had an increased risk for readmission and ED visit. CONCLUSIONS: Post
      discharge readmissions and ED visits are relatively common after pediatric
      surgery, particularly for AT. Perioperative treatment algorithms that consider
      risk factors for hospital revisits are required in children.

PMID- 28432614
TI  - Dual Activity of Hydroxypropyl-beta-Cyclodextrin and Water-Soluble Carriers on
      the Solubility of Carvedilol.
AB  - Carvedilol (CAR) is a non-selective alpha and beta blocker categorized as class
      II drug with low water solubility. Several recent studies have investigated ways
      to overcome this problem. The aim of the present study was to combine two of
      these methods: the inclusion complex using hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) with solid dispersion using two carriers: Poloxamer 188 (PLX) and
      Polyvinylpyrrolidone K-30 (PVP) to enhance the solubility, bioavailability, and
      the stability of CAR. Kneading method was used to prepare CAR-HPbetaCD inclusion
      complex (KD). The action of different carriers separately and in combination on
      Carvedilol solubility was investigated in three series. CAR-carrier and KD
      carrier solid dispersions were prepared by solvent evaporation method. In vitro
      dissolution test was conducted in three different media: double-distilled water
      (DDW), simulative gastric fluid (SGF), and PBS pH 6.8 (PBS). The interactions
      between CAR, HPbetaCD, and different carriers were explored by Fourier transform
      infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), and differential
      scanning colorimetry (DSC). The results showed higher solubility of CAR in KD-PVP
      solid dispersions up to 70, 25, and 22 fold compared to pure CAR in DDW, SGF, and
      PBS, respectively. DSC and XRD analyses indicated an improved degree of
      transformation of CAR in KD-PVP solid dispersion from crystalline to amorphous
      state. This study provides a new successful combination of two polymers with the
      dual action of HPbetaCD and PLX/PVP on water solubility and bioavailability of
      CAR.

PMID- 28432615
TI  - Fabrication, Physicochemical Characterization, and Performance Evaluation of
      Biodegradable Polymeric Microneedle Patch System for Enhanced Transcutaneous Flux
      of High Molecular Weight Therapeutics.
AB  - A revolutionary paradigm shift is being observed currently, towards the use of
      therapeutic biologics for disease management. The present research was focused on
      designing an efficient dosage form for transdermal delivery of alpha
      choriogonadotropin (high molecular weight biologic), through biodegradable
      polymeric microneedles. Polyvinylpyrrolidone-based biodegradable microneedle
      arrays loaded with high molecular weight polypeptide, alpha-choriogonadotropin,
      were fabricated for its systemic delivery via transdermal route. Varied process
      and formulation parameters were optimized for fabricating microneedle array,
      which in turn was expected to temporally rupture the stratum corneum layer of the
      skin, acting as a major barrier to drug delivery through transdermal route. The
      developed polymeric microneedles were optimized on the basis of quality
      attributes like mechanical strength, axial strength, insertion ratio, and
      insertion force analysis. The optimized polymeric microneedle arrays were
      characterized for in vitro drug release studies, ex vivo drug permeation studies,
      skin resealing studies, and in vivo pharmacokinetic studies. Results depicted
      that fabricated polymeric microneedle arrays with mechanical strength of above 5
      N and good insertion ratio exhibited similar systemic bioavailability of alpha
      choriogonadotropin in comparison to marketed subcutaneous injection formulation
      of alpha-choriogonadotropin. Thus, it was ultimately concluded that the designed
      drug delivery system can serve as an efficient tool for systemic delivery of
      therapeutic biologics, with an added benefit of overcoming the limitations of
      parenteral delivery, achieving better patient acceptability and compliance.

PMID- 28432616
TI  - Prognostic impact of PD-1 and its ligands in renal cell carcinoma.
AB  - Programmed death-1 receptor (PD-1) and programmed death-1 receptor-ligand (PD-L1)
      have been suggested to play a role as prognostic markers in clear cell renal cell
      carcinoma (ccRCC). The association between PD-L1 and prognosis seems to be more
      robust than for PD-1. Further, preliminary analyses suggest that neither PD-1 nor
      its ligands play a role as prognostic markers in non-clear cell RCC, while the
      prognostic role of PD-L2 in ccRCC as well as in non-clear cell RCC remains
      unclear.

PMID- 28432617
TI  - Prognostic significance of histologic subtype in pStage I lung adenocarcinoma.
AB  - The International Association for the Study of Lung Cancer, the American Thoracic
      Society, and the European Respiratory Society (IASLC/ATS/ERS) proposed a new
      histologic classification of lung adenocarcinoma in 2011. While several studies
      have already validated the prognostic value of this new classification of lung
      adenocarcinoma, we conducted own investigation in the present study. This study
      included 197 patients with invasive lung adenocarcinoma who underwent complete
      resection. Pathologic diagnoses were made in accordance with the new
      IASLC/ATS/ERS classification for lung adenocarcinoma. The
      lepidic/acinar/papillary group had a significantly better prognosis than the
      micropapillary/solid/invasive mucinous adenocarcinoma group (5-year recurrence
      free survival [RFS] 73 vs. 21%: p < 0.01, 5-year overall survival 85 vs. 52%: p <
      0.01). Age (hazard ratio [HR], 1.898; p = 0.03), CEA (HR, 1.873; p = 0.03),
      pStage (HR, 6.149; p < 0.01), and histologic subtype (HR, 2.342; p = 0.01) were
      independent prognostic factors for the RFS. Furthermore, age (HR, 3.242; p =
      0.04), CEA (HR, 3.405; p = 0.03) and histologic subtype (HR, 11.108; p < 0.01)
      were independent prognostic factors for the progression-free survival in pStage
      I. The histologic subtype correlated with the prognosis of pStage I of lung
      adenocarcinoma. Patients in the high-grade group of lung adenocarcinoma, which
      included solid, micropapillary and invasive mucinous adenocarcinoma with pStage
      I, should be considered candidates for postoperative adjuvant therapy.

PMID- 28432618
TI  - The identification of key genes and pathways in hepatocellular carcinoma by
      bioinformatics analysis of high-throughput data.
AB  - Liver cancer is a serious threat to public health and has fairly complicated
      pathogenesis. Therefore, the identification of key genes and pathways is of much
      importance for clarifying molecular mechanism of hepatocellular carcinoma (HCC)
      initiation and progression. HCC-associated gene expression dataset was downloaded
      from Gene Expression Omnibus database. Statistical software R was used for
      significance analysis of differentially expressed genes (DEGs) between liver
      cancer samples and normal samples. Gene Ontology (GO) term enrichment analysis
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, based on R
      software, were applied for the identification of pathways in which DEGs
      significantly enriched. Cytoscape software was for the construction of protein
      protein interaction (PPI) network and module analysis to find the hub genes and
      key pathways. Finally, weighted correlation network analysis (WGCNA) was
      conducted to further screen critical gene modules with similar expression pattern
      and explore their biological significance. Significance analysis identified 1230
      DEGs with fold change >2, including 632 significantly down-regulated DEGs and 598
      significantly up-regulated DEGs. GO term enrichment analysis suggested that up
      regulated DEG significantly enriched in immune response, cell adhesion, cell
      migration, type I interferon signaling pathway, and cell proliferation, and the
      down-regulated DEG mainly enriched in response to endoplasmic reticulum stress
      and endoplasmic reticulum unfolded protein response. KEGG pathway analysis found
      DEGs significantly enriched in five pathways including complement and coagulation
      cascades, focal adhesion, ECM-receptor interaction, antigen processing and
      presentation, and protein processing in endoplasmic reticulum. The top 10 hub
      genes in HCC were separately GMPS, ACACA, ALB, TGFB1, KRAS, ERBB2, BCL2, EGFR,
      STAT3, and CD8A, which resulted from PPI network. The top 3 gene interaction
      modules in PPI network enriched in immune response, organ development, and
      response to other organism, respectively. WGCNA revealed that the confirmed eight
      gene modules significantly enriched in monooxygenase and oxidoreductase activity,
      response to endoplasmic reticulum stress, type I interferon signaling pathway,
      processing, presentation and binding of peptide antigen, cellular response to
      cadmium and zinc ion, cell locomotion and differentiation, ribonucleoprotein
      complex and RNA processing, and immune system process, respectively. In
      conclusion, we identified some key genes and pathways closely related with HCC
      initiation and progression by a series of bioinformatics analysis on DEGs. These
      screened genes and pathways provided for a more detailed molecular mechanism
      underlying HCC occurrence and progression, holding promise for acting as
      biomarkers and potential therapeutic targets.

PMID- 28432619
TI  - Assessment of Saxagliptin Efficacy: Meta-Analysis of 14 Phase 2 and 3 Clinical
      Trials.
AB  - INTRODUCTION: This meta-analysis of data from 14 phase 2 and 3, double-blind,
      randomized, controlled 12- and 24-week studies (N = 4632) summarizes saxagliptin
      efficacy in patients with type 2 diabetes (T2D) across treatment regimens.
      METHODS: Patients received saxagliptin 5 mg/d or control as either monotherapy (n
      = 1196 vs placebo), add-on therapy (n = 2139 vs placebo and n = 514 vs uptitrated
      sulfonylurea), or initial combination therapy (n = 619 vs control monotherapy).
      Patients with renal impairment received saxagliptin 2.5 mg/d or placebo (n =
      164). RESULTS: Mean baseline glycated hemoglobin (A1C) ranged from 8.07% to 9.43%
      for the saxagliptin and control groups across treatment regimens. A1C reduction
      from baseline was greater with saxagliptin versus control for all studies
      combined (mean treatment difference [95% CI]: -0.55% [-0.63%, -0.47%]) and when
      used as monotherapy (-0.52% [-0.63, -0.40%]), add-on (-0.55% [-0.69%, -0.40%] vs
      placebo; -0.72% [-0.88%, -0.56%] vs uptitrated sulfonylurea), initial combination
      therapy (-0.54% [-0.73%, -0.35%] vs control monotherapy), and in patients with
      renal impairment (-0.42% [-0.75%, -0.09%]). Similar reductions in A1C versus
      control were noted for patients <65 years (-0.55% [-0.67%, -0.43%]) and >=65
      years (-0.54% [-0.69%, -0.38%]) and for men (-0.54% [-0.69%, -0.40%]) and women (
      0.55% [-0.64%, -0.47%]) across treatment regimens. More patients achieved A1C <7%
      (39% vs 23%) and A1C <=6.5% (24% vs 14%) with saxagliptin than with placebo or
      active-control treatment. Saxagliptin versus control was associated with a
      reduction in glucagon area under the curve (AUC) from baseline and increases in
      insulin AUC, C-peptide AUC, and the homeostasis model assessment of beta-cell
      function. CONCLUSION: Results of this meta-analysis demonstrate the consistency
      of saxagliptin efficacy in different subgroups of patients with T2D across
      treatment regimens. FUNDING: AstraZeneca.

PMID- 28432620
TI  - Cultivating hope for a better future: research contributions from young scholars
      in earth and environmental sciences.

PMID- 28432621
TI  - Comparison of air pollution in Shanghai and Lanzhou based on wavelet transform.
AB  - For a long-period comparative analysis of air pollution in coastal and inland
      cities, we analyzed the continuous Morlet wavelet transform on the time series of
      a 5274-day air pollution index in Shanghai and Lanzhou during 15 years and
      studied the multi-scale variation characteristic, main cycle, and impact factor
      of the air pollution time series. The analysis showed that (1) air pollution in
      the two cities was non-stationary and nonlinear, had multiple timescales, and
      exhibited the characteristics of high in winter and spring and low in summer and
      autumn. (2) The monthly variation in air pollution in Shanghai was not
      significant, whereas the seasonal variation of air pollution in Lanzhou was
      obvious. (3) Air pollution in Shanghai showed an ascending tendency, whereas that
      in Lanzhou presented a descending tendency. Overall, air pollution in Lanzhou was
      higher than that in Shanghai, but the situation has reversed since 2015. (4) The
      primary cycles of air pollution in these two cities were close, but the secondary
      cycles were significantly different. The aforementioned differences were mainly
      due to the impact of topographical and meteorological factors in Lanzhou, the
      weather process and the surrounding environment in Shanghai. These conclusions
      have reference significance for Shanghai and Lanzhou to control air pollution.
      The multi-timescale variation and local features of the wavelet analysis method
      used in this study can be applied to varied aspects of air pollution analysis.
      The identification of cycle characteristics and the monitoring, forecasting, and
      controlling of air pollution can yield valuable reference.

PMID- 28432622
TI  - Diversity shift in bacterial phenol hydroxylases driven by alkyl-phenols in oil
      refinery wastewaters.
AB  - Phenol hydroxylases (PHs) play a primary role in the bacterial degradation of
      phenol and alkylphenols. They are divided into two main classes, single-component
      and multi-component PHs, having distinctive catalytic subunits designated as
      PheA1 and LmPH, respectively. The diversity of these enzymes is still largely
      unexplored. Here, both LmPH and pheA1 gene sequences were examined in activated
      sludge from oil refinery wastewaters. Phenol, p-cresol, or 3,4-dimethylphenol
      (3,4-DMP) supplied as extra carbon sources were rapidly mineralized by the
      microbial community. Analysis of LmPH genes revealed a wide range of sequences,
      most of which exhibited moderate similarity with homologs found in
      Proteobacteria. Moreover, the LmPH diversity profiles showed a dramatic shift
      upon sludge treatment with p-cresol or 3,4-DMP amendment. This resulted in an
      enrichment in sequences similar to LmPHs from Betaproteobacteria and
      Gammaproteobacteria. RT-PCR analysis of RNA extracted from wastewater sludge
      highlighted LmPH genes best expressed in situ. A PCR approach was implemented to
      analyze the pheA1 gene diversity in the same microbial community. Retrieved
      sequences fell into four clusters and appeared to be distantly related to pheA1
      genes from Actinobacteria. Altogether, our results provide evidence that phenol
      degraders carrying LmPH are more diverse than PheA1 carrying bacteria and suggest
      that PHs with best adapted substrate specificity are recruited in response to
      (methyl)phenol availability.

PMID- 28432623
TI  - Performance of CSTR-EGSB-SBR system for treating sulfate-rich cellulosic ethanol
      wastewater and microbial community analysis.
AB  - Performance and microbial community composition were evaluated in a two-phase
      anaerobic and aerobic system treating sulfate-rich cellulosic ethanol wastewater
      (CEW). The system was operated at five different chemical oxygen demand
      (COD)/SO42- ratios (63.8, 26.3, 17.8, 13.7, and 10.7). Stable performance was
      obtained for total COD removal efficiency (94.5%), sulfate removal (89.3%), and
      methane production rate (11.5 L/day) at an organic loading rate of 32.4 kg
      COD/(m3.day). The acidogenic reactor made a positive contribution to net VFAs
      production (2318.1 mg/L) and sulfate removal (60.9%). Acidogenic bacteria
      (Megasphaera, Parabacteroides, unclassified Ruminococcaceae spp., and Prevotella)
      and sulfate-reducing bacteria (Butyrivibrio, Megasphaera) were rich in the
      acidogenic reactor. In the methanogenic reactor, high diversity of microorganisms
      corresponded with a COD removal contribution of 83.2%. Moreover, methanogens
      (Methanosaeta) were predominant, suggesting that these organisms played an
      important role in the acetotrophic methanogenesis pathway. The dominant aerobic
      bacteria (Truepera) appeared to have been responsible for the COD removal of the
      SBR. These results indicate that dividing the sulfate reduction process could
      effectively minimize sulfide toxicity, which is important for the successful
      operation of system treating sulfate-rich CEW.

PMID- 28432624
TI  - Delivering environmental benefit from the use of Environmental Quality Standards:
      why we need to focus on implementation.
AB  - The UK has adopted a broader approach to the introduction of Environmental
      Quality Standard (EQS) for the aquatic environment than many other jurisdictions
      around the world, with a greater focus on the implementation of scientifically
      derived standards. This follows the publication of a report by the Royal
      Commission on Environmental Pollution in 1998 which drew attention to the need to
      recognise that whilst an EQS is often just viewed as a numerical value, it also
      has other important characteristics that need to be recognised if it is to be a
      practical and effective regulatory tool. One of the aspects that has not always
      been recognised was that of implementation assessment, i.e. the steps needed to
      ensure that a standard actually delivers environmental benefit or improvements.
      In many jurisdictions, there is considerable technical and sometimes political
      emphasis on the numerical value of the EQS (e.g. the critical concentration in an
      environmental matrix like water), including the method of derivation, the
      scrutiny of the reliability and relevance of the ecotoxicity test data and
      extensive deliberations of unquantified uncertainties in relation to the choice
      of assessment factor. The regulatory value of an EQS only comes through a
      comparison against a measured environmental concentration, yet only relatively
      limited regulatory effort has historically been expended on this component of the
      classic environmental risk assessment paradigm. For example, there needs to be an
      acceptable (i.e. small) uncertainty in the EQS, an appropriate analytical method
      and detection limit in the correct matrix, a method to deliver a comparison with
      the EQS and a robust statistical method to draw unbiased conclusions about
      environmental risk. In addition, we argue that there is a case for checking the
      consequences of introducing a standard against field data, wherever possible.
      This validation of the EQS rarely happens currently. We explain what
      implementation assessment is and why it is needed. We give examples of how
      implementation assessment can be integrated with EQS derivation and also present
      examples of what happens when the focus is only upon the derivation of a
      numerical value. It is clear from this evidence that advances in derivation
      methods need to be coupled with practical solutions of implementation if we are
      to realise environmental benefit from an EQS in a cost-effective manner.

PMID- 28432625
TI  - Synthesis of magnetic CoFe2O4/ordered mesoporous carbon nanocomposites and
      application in Fenton-like oxidation of rhodamine B.
AB  - CoFe2O4/ordered mesoporous carbon (OMC) nanocomposites were synthesized and
      tested as heterogeneous peroxymonosulfate (PMS) activator for the removal of
      rhodamine B. Characterization confirmed that CoFe2O4 nanoparticles were tightly
      bonded to OMC, and the hybrid catalyst possessed high surface area, pore volume,
      and superparamagnetism. Oxidation experiments demonstrated that CoFe2O4/OMC
      nanocomposites displayed favorable catalytic activity in PMS solution and
      rhodamine B degradation could be well described by pseudo-first-order kinetic
      model. Sulfate radicals (SO4-.) were verified as the primary reactive species
      which was responsible for the decomposition of rhodamine B. The optimum loading
      ratio of CoFe2O4 and OMC was determined to be 5:1. Under optimum operational
      condition (catalyst dosage 0.05 g/L, PMS concentration 1.5 mM, pH 7.0, and 25 
      degrees C), CoFe2O4/OMC-activated peroxymonosulfate system could achieve almost
      complete decolorization of 100 mg/L rhodamine B within 60 min. The enhanced
      catalytic activity of CoFe2O4/OMC nanocomposites compared to that of CoFe2O4
      nanoparticles could be attributable to the increased adsorption capacity and
      accelerated redox cycles between Co(III)/Co(II) and Fe(III)/Fe(II).

PMID- 28432627
TI  - Inorganic fouling control in reverse osmosis wastewater reclamation by purging
      carbon dioxide.
AB  - Inorganic fouling on the membrane surface is one of the major prevalent issues
      affecting the performance and cost of reverse osmosis system. Chemical dosage is
      a widely adopted method for the inhibition of inorganic scale on the membrane
      surface. In this study, CO2 was used to control inorganic scale formation on
      surface of reverse osmosis (RO) membrane in wastewater reclamation. The pH of
      influent could be lowered by purging CO2. It caused an increase in solubility of
      inorganic salts in water resulting in discharge of principle ions in concentrate
      stream. A pilot plant study was conducted with four different RO modules
      including control, with dosage of antiscalant, with purging CO2 and with co
      addition of antiscalant and CO2. The effectiveness of CO2 purging was assessed on
      the basis of operational analysis, in-line analysis and morphological results.
      Ryznar stability index was used to determine the scaling potential of system. The
      examined data indicated that CO2 purging was successful to inhibit scale
      formation on the membrane surface. Moreover, CO2 was found more eco-friendly than
      antiscalant, as no by-products were generated in concentrate stream.

PMID- 28432626
TI  - Temporal trends of lipophilic persistent organic pollutants in serum from Danish
      nulliparous pregnant women 2011-2013.
AB  - The use of the lipophilic persistent organic pollutants (POPs) including
      polychlorinated biphenyls (PCBs) and several organochlorine pesticides (OCPs) has
      been prohibited for more than 30 years. In this study, we present the temporal
      trends of the lipophilic POP serum concentrations in Danish nulliparous pregnant
      women between 2011 and 2013. We randomly selected 197 pregnant women (gestational
      age 11-13) from the Aarhus Birth Cohort. The concentrations of the lipophilic
      POPs in the serum samples were analyzed using gas chromatography. The
      concentrations were corrected for total serum lipids. The statistical analysis
      was performed by regression analysis with adjustment for age, BMI, gestational
      age at blood draw, and smoking status. The serum concentrations of PCB 118, 138,
      153, 156, 170, 180, 187, and hexachlorobenzen, trans-nonachlor, beta
      hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene were
      lower in 2013 than in 2011. However, the oxychlordane concentration was lowest in
      2011. The serum levels of most lipophilic POPs followed downward trends during
      the study period, which was expected, as these compounds has been banned for many
      years. The upward trend of oxychlordane was unexpected and presumably a chance
      finding.

PMID- 28432628
TI  - Design of water quality monitoring networks with two information scenarios in
      tropical Andean basins.
AB  - Design and redesign of water quality monitoring networks were evaluated for two
      similarly sized watersheds in the tropical Andes via optimization techniques
      using geographic information system technology (GIS) and a matter-element
      analysis of 5-day biological oxygen demand (BOD5) and total suspended solids
      (TSS). This resulted in a flexible, objectively based design for a 1128-km2
      watershed without prior water quality data (La Miel River), and a network
      redesign of a 1052-km2 watershed with historical water quality monitoring
      (Chinchina River). Monitoring design for the undocumented basin incorporated
      mathematical expressions for physical, anthropological, and historical factors
      and was based on clear objectives for diagnosis and intervention of water
      pollution. Network redesign identified network redundancy, which resulted in a
      64% reduction in the number of water quality monitoring stations along the
      channel, and a 78% reduction of stations throughout the basin. Most tropical
      drainage basins throughout the world have little to no prior water quality data.
      But even in well-studied drainage basins like the Chinchina River, which is among
      the most thoroughly studied basins in Colombia, redesign of historical and
      existing monitoring networks will become a standard tool to advance the
      restoration of polluted surface waters, not only in Colombia, but also throughout
      the world.

PMID- 28432629
TI  - Aquatic photolysis of hydroxylated polybromodiphenyl ethers under direct UV
      irradiation: a case study of 2'-HO-BDE-68.
AB  - Hydroxylated polyhalodiphenyl ethers (HO-PXDEs) have attracted considerable
      scientific interest as examples of emerging aquatic pollutants. However, a
      comprehensive assessment of disposal methods for this particular pollutant was
      seldom investigated. This study examined the UV light degradation of HO-PXDEs,
      using 2'-HO-2, 3', 4, 5'-tetrabromodiphenyl ether (2'-HO-BDE-68) as a case study.
      The results showed that UV light was superior to visible light and electron beam
      irradiation for producing a high degradation rate of 2'-HO-BDE-68. At low
      concentrations of HO-BDE, the degradation rate was not obviously improved with
      decreasing initial concentration. The degradation efficiency was also found to be
      better in alkaline solutions. In a UV/H2O2 system, the hydroxyl radical provided
      by H2O2 was shown to enhance the degradation efficiency. The main photolysis
      products of 2'-HO-BDE-68 were identified, and the possible photodegradation
      pathways were proposed. 1, 3, 8-Tribromodibenzo-p-dioxin was one of the
      photoproducts, which indicates that secondary pollution must also be considered
      with the UV photolysis process.

PMID- 28432630
TI  - The influence of restoration measures on phosphorus internal loading from the
      sediments of a hypereutrophic lake.
AB  - Uzarzewskie Lake was a hypereutrophic, dimictic lake characterized by low water
      transparency, high chlorophyll-a concentration and intense phytoplankton blooms;
      thus, restoration treatment was started. A chemical treatment, based on
      phosphorus inactivation with small doses of iron sulphate, was undertaken in 2006
      2007. Nitrate-rich groundwater flowing from seepage springs was directed into the
      lake hypolimnion to increase redox potential since 2008. Phosphorus internal
      loading was reduced by more than 80% as a result of restoration treatment. In the
      profundal zone, where P release from the bottom sediments prevailed throughout
      the year, it decreased from 13.02 mg P m-2 day-1 in 2010 to 2.81 mg P m-2 day-1
      in 2015. Meanwhile, in the littoral zone, P accumulation in bottom sediments
      predominated; hence, the mean value of internal loading was increasing from 2.61
      mg P m-2 day-1 in 2011 to 10.24 mg P m-2 day-1 in 2015. The annual P load from
      the bottom sediments in the profundal zone was much higher than from the littoral
      zone as a result of (i) a higher P release in most years and (ii) the greater
      area of this zone (82% of the lake's area). The fraction of residual phosphorus
      (Res-P) has the largest share, and in recent years, this has shown a tendency to
      decrease. The sum of bioavailable fractions was low (average 5.7%) showing a
      downward trend in recent years. Sustainable restoration of the lake resulted in a
      slow but steady decreasing trend in internal phosphorus loading.

PMID- 28432631
TI  - Coumarin-Based Fluorescent Probe for Hypochlorites and Real Application in Tap
      Water.
AB  - Taking advantages of both the oxidation property of hypochlorite and different
      coordination properties of Cu+ and Cu2+ ions, we developed a new fluorescent
      probe for hypochlorite anion, namely, compound C1. In the presence of ClO-, the
      sensing system displayed extraordinary fluorescence quenching, which was
      beneficial to the production of a high signal output during detection process. By
      virtue of its special oxidation property, the probe displayed high selectivity
      for ClO- over other anions. Moreover, this novel sensing system could be used for
      the analysis of ClO- levels in tap water and potentially in environmental
      samples.

PMID- 28432632
TI  - Tryptophan Fluorescence Yields and Lifetimes as a Probe of Conformational Changes
      in Human Glucokinase.
AB  - Five variants of glucokinase (ATP-D-hexose-6-phosphotransferase, EC 2.7.1.1)
      including wild type and single Trp mutants with the Trp residue at positions 65,
      99, 167 and 257 were prepared. The fluorescence of Trp in all locations studied
      showed intensity changes when glucose bound, indicating that conformational
      change occurs globally over the entire protein. While the fluorescence quantum
      yield changes upon glucose binding, the enzyme's absorption spectra, emission
      spectra and fluorescence lifetimes change very little. These results are
      consistent with the existence of a dark complex for excited state Trp. Addition
      of glycerol, L-glucose, sucrose, or trehalose increases the binding affinity of
      glucose to the enzyme and increases fluorescence intensity. The effect of these
      osmolytes is thought to shift the protein conformation to a condensed, high
      affinity form. Based upon these results, we consider the nature of quenching of
      the Trp excited state. Amide groups are known to quench indole fluorescence and
      amides of the polypeptide chain make interact with excited state Trp in the
      relatively unstructured, glucose-free enzyme. Also, removal of water around the
      aromatic ring by addition of glucose substrate or osmolyte may reduce the
      quenching.

PMID- 28432634
TI  - New Chromophore Systems from Coumarin-Oxazol-5-one Combination.
AB  - Coumarin-oxazol-5-one (COX), 3a-d, were synthesized with 7-methoxy-2-oxo-2H
      chromene-4-carbaldehyde and benzoylglycine derivatives. The characterizations of
      the COX derivatives by 1H NMR, FT-IR and elemental analysis were achieved. To
      obtain the photophysical data of the synthesized COX derivatives were used
      spectrophotometric and spectrofluorimetric methods. Evaluation of the absorption
      and emission properties of the structures was carried out in six different
      solvents. Maximum absorption and emission wavelengths (lambda; nm), molar
      extinction coefficients (epsilon; cm-1 M-1), Stoke's shifts (DeltalambdaST; nm)
      and quantum yields (phiF), of the COX derivatives were declared.

PMID- 28432633
TI  - Synthesis, Spectral Properties and DFT Calculations of new Ruthenium (II)
      Polypyridyl Complexes; DNA Binding Affinity and in Vitro Cytotoxicity Activity.
AB  - In this paper a novel ligand debip (2-(4-N,N-diethylbenzenamine)1H-imidazo[4,5-f]
      [1, 10]phenanthroline) and its Ru(II) polypyridyl complexes [Ru(L)2(debip)]2+, (L
      = phen (1), bpy (2) and dmb (3)) have been synthesized and characterized by
      spectroscopic techniques. The DNA binding studies for all these complexes were
      examined by absorption, emission, quenching studies, viscosity measurements and
      cyclic voltammetry. The light switching properties of complexes 1-3 have been
      evaluated. Molecular docking, Density Functional Theory (DFT) and time dependent
      DFT calculations were performed. The Ru(II) complexes exhibited efficient
      photocleavage activity against pBR322 DNA upon irradiation and exhibited good
      antimicrobial activity. Also investigated 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) reduction assay, lactate dehydrogenase (LDH)
      release assay and reactive oxygen species (ROS) against selected cancer cell
      lines (HeLa, PC3, Lancap, MCF-7 and MD-MBA 231).

PMID- 28432635
TI  - Role of Inflammation in Heart Failure.
AB  - PURPOSE OF REVIEW: This paper aims to discuss the interactions between
      inflammatory cytokines, immune cells, and heart failure (HF). The association of
      heart failure with inflammation has led to multiple studies on anti-inflammatory
      agents in acute and chronic heart failure. RECENT FINDINGS: Recent findings have
      implicated leukocytes subclasses and multiple inflammatory mediators in the
      progression of heart failure and cardiovascular disease. Studies have discovered
      further details on the interaction between immune cells-particularly macrophages
      and lymphocytes-and inflammation. There are both cell-mediated and cytokine
      mediated pathways of inflammation, which are interconnected. Additionally, a
      number of markers have been used and studied in heart failure disease
      progression. In this review, we discuss inflammatory biomarkers and immune cell
      mediators involved in HF. We will focus on the correlations and role of these
      inflammatory mediators in the genesis of HF. We will also discuss the evidence on
      beneficial effects of anti-inflammatory agents in the setting of chronic HF.

PMID- 28432636
TI  - What is the Current Knowledge About the Cardiovascular Risk for Users of Cannabis
      Based Products? A Systematic Review.
AB  - PURPOSE OF REVIEW: The purpose of the study was to examine the published evidence
      on the cardiovascular risk related to the use of cannabis-based products by
      performing a systematic review of recent literature. RECENT FINDINGS: The World
      Health Organization (WHO) emphasizes that cannabis use represents a risky
      behavior as it may lead to many adverse effects, and in particular,
      cardiovascular effects. A systematic review of articles published between January
      1, 2011 and May 31, 2016 was performed in agreement with the PRISMA statement.
      Articles presenting data on humans exposed to cannabis-based products and
      suffering from any cardiovascular condition were eligible for inclusion. The
      inclusion process was based on a search algorithm and performed in a blinded
      standardized manner. Overall, 826 articles were found in the literature search,
      115 of which remained after performing the inclusion procedure. These were 81
      case reports, 29 observational studies, 3 clinical trials, and 2 experimental
      studies. A total of 116 individuals was the subject of case reports. The mean age
      was 31 years (95%CI = 29-34), and patients were more frequently men (81.9%) than
      women (18.1%). They mainly suffered from ischemic strokes or myocardial
      infarctions. Data provided by the 29 included observational studies evidenced an
      association between exposure to cannabis-based products and cardiovascular
      disease. Currently, this evidence is stronger for ischemic strokes than for any
      other cardiovascular diseases. While the data are limited, there is some
      suggestion that cannabis use may have negative cardiovascular consequences,
      particularly at large doses.

PMID- 28432638
TI  - Community Gardens as Environmental Health Interventions: Benefits Versus
      Potential Risks.
AB  - PURPOSE OF REVIEW: The purpose of this paper was to summarize current findings on
      community gardens relevant to three specific areas of interest as follows: (1)
      health benefits, (2) garden interventions in developing versus developed
      countries, and (3) the concerns and risks of community gardening. RECENT
      FINDINGS: Community gardens are a reemerging phenomenon in many low- and high
      income urban neighborhoods to address the common risk factors of modern
      lifestyle. Community gardens are not limited to developed countries. They also
      exist in developing low-income countries but usually serve a different purpose of
      food security. Despite their benefits, community gardens can become a source of
      environmental toxicants from the soil of mostly empty lands that might have been
      contaminated by toxicants in the past. Therefore, caution should be taken about
      gardening practices and the types of foods to be grown on such soil if there was
      evidence of contamination. We present community gardens as additional solutions
      to the epidemic of chronic diseases in low-income urban communities and how it
      can have a positive physical, mental and social impact among participants. On
      balance, the benefits of engaging in community gardens are likely to outweigh the
      potential risk that can be remedied. Quantitative population studies are needed
      to provide evidence of the benefits and health impacts versus potential harms
      from community gardens.

PMID- 28432639
TI  - Measuring patient experience in dialysis: a new paradigm of quality assessment.
AB  - Patients' experience of care (PEC) is as an important dimension in quality of
      care. As a distinct entity from patient satisfaction and patient health-related
      quality of life, PEC is defined as patients' perceptions of the range of
      interactions they have with the health care system, including care from
      providers, facilities, and health plans. While traditionally PEC may be
      ascertained via informal assessments, in recent years, especially in the United
      States, there has been a shift towards standardized surveillance of PEC amongst
      dialysis patients in order to: (1) set a normative expectation regarding the
      importance of PEC; (2) standardize the components of patients' experience that
      are assessed to minimize potential "blind spots"; (3) provide a direct "voice" to
      the patient in communicating perceptions of their care; (4) facilitate
      comparisons of quality across facilities; and (5) broaden accountability for PEC
      to the entire multidisciplinary dialysis care team. In this review, we will
      discuss the significance of PEC as a quality of care metric in dialysis patients;
      the history of PEC assessment across other health care arenas; the development of
      the In-Center Hemodialysis Consumer Assessment of Healthcare Provider and Systems
      survey as a means to standardize PEC assessment among US dialysis patients;
      experiences in PEC assessment across international dialysis populations; and
      future areas of research needed to refine the ascertainment of PEC and its impact
      upon patient outcomes.

PMID- 28432637
TI  - Polluted Pathways: Mechanisms of Metabolic Disruption by Endocrine Disrupting
      Chemicals.
AB  - PURPOSE OF REVIEW: Environmental toxicants are increasingly implicated in the
      global decline in metabolic health. Focusing on diabetes, herein, the molecular
      and cellular mechanisms by which metabolism disrupting chemicals (MDCs) impair
      energy homeostasis are discussed. RECENT FINDINGS: Emerging data implicate MDC
      perturbations in a variety of pathways as contributors to metabolic disease
      pathogenesis, with effects in diverse tissues regulating fuel utilization.
      Potentiation of traditional metabolic risk factors, such as caloric excess, and
      emerging threats to metabolism, such as disruptions in circadian rhythms, are
      important areas of current and future MDC research. Increasing evidence also
      implicates deleterious effects of MDCs on metabolic programming that occur during
      vulnerable developmental windows, such as in utero and early post-natal life as
      well as pregnancy. Recent insights into the mechanisms by which MDCs alter energy
      homeostasis will advance the field's ability to predict interactions with
      classical metabolic disease risk factors and empower studies utilizing targeted
      therapeutics to treat MDC-mediated diabetes.

PMID- 28432640
TI  - Osteoporosis, bone mineral density and CKD-MBD: treatment considerations.
AB  - Osteoporosis and chronic kidney disease (CKD) have both independently important
      potential impact on bone health. A significant number of patients with CKD stages
      3a-5D have been shown to have low bone mineral density (BMD), leading to a
      strikingly elevated risk of fractures (mainly hip fractures) and higher
      associated morbidity and mortality. Mechanical properties of bone beyond age and
      menopausal status are additionally affected by intrinsic uremic factors.
      Therefore, we review in this article not only general concepts of osteoporosis
      and related consequences, but also the diagnostic and therapeutic implications of
      low BMD and bone fractures in CKD, beyond increased vascular calcification.
      Antiresorptive agents (mainly bisphosphonates) were not previously recommended
      when the estimated glomerular filtration rate (GFR) was lower than 30 ml/min/1.73
      m2. However, post-hoc analysis of large randomized clinical trials found that
      these drugs (i.e. alendronate, ribandronate, denosumab) had comparable efficacy
      in improving BMD and reducing fracture risk in individuals (mainly women) with
      moderate reductions of GFR (mostly CKD stages 3-4). Therefore, at least in the
      absence of clear abnormalities of CKD-related mineral metabolism disturbances,
      bone antiresorptive agents (and maybe anabolic agents) that are or will be
      approved for general osteoporosis may be appropriate for CKD. Nephrologists
      should probably not ignore any longer fracture risk assessment, especially in
      patients with additional risk factors for osteoporosis if results will impact
      treatment decisions. However, although different therapeutic agents have been
      shown to reduce the risk of fracture in CKD patients with low BMD, specific
      prospective studies, with or without bone biopsies, in CKD are urgently needed.

PMID- 28432641
TI  - Dentatorubro-Pallidoluysian Atrophy (DRPLA) among 700 Families with Ataxia in
      Brazil.
AB  - Dentatorubro-pallidoluysian atrophy (DRPLA) is a spinocerebellar ataxia (SCA)
      very rare in non-Asian populations. To date, DRPLA was undetected in the general
      Brazilian population. Adult-onset ataxic patients have been recruited from
      several Brazilian neurology and neurogenetics centers. CAG lengths at SCA1, SCA2,
      SCA3/MJD, SCA6, SCA7, SCA12, SCA17 and DRPLA associated genes, and ATTCT
      expansions at SCA10 gene were studied. A single DRPLA case detected is reported.
      Proband was a 69-year-old Brazilian woman of mixed ancestry, with a late-onset
      pure ataxia: her alleles at the associated gene, ATN1, presented 14/52 CAG
      repeats. History of gait ataxia and dementia was observed in two out of six
      siblings but was absent in her parents. This was the single DRPLA diagnosis
      obtained from 700 Brazilian unrelated cases with adult-onset ataxia, 487 of them
      with clear autosomal dominant inheritance. DRPLA accounted for 0.14% of all adult
      onset ataxia cases and for 0.2% of families with autosomal dominant inheritance.
      Normal CAG repeats at ATN1 had a median (range) of 14 (5-20) repeats in other 410
      Brazilian chromosomes. DRPLA is quite rare in Brazilian SCA families, which is
      consistent with the lack of large normal alleles in our population.

PMID- 28432642
TI  - Emerging Use of Early Health Technology Assessment in Medical Product
      Development: A Scoping Review of the Literature.
AB  - Early health technology assessment is increasingly being used to support health
      economic evidence development during early stages of clinical research. Such
      early models can be used to inform research and development about the design and
      management of new medical technologies to mitigate the risks, perceived by
      industry and the public sector, associated with market access and reimbursement.
      Over the past 25 years it has been suggested that health economic evaluation in
      the early stages may benefit the development and diffusion of medical products.
      Early health technology assessment has been suggested in the context of iterative
      economic evaluation alongside phase I and II clinical research to inform clinical
      trial design, market access, and pricing. In addition, performing early health
      technology assessment was also proposed at an even earlier stage for managing
      technology portfolios. This scoping review suggests a generally accepted
      definition of early health technology assessment to be "all methods used to
      inform industry and other stakeholders about the potential value of new medical
      products in development, including methods to quantify and manage uncertainty".
      The present review also aimed to identify recent published empirical studies
      employing an early-stage assessment of a medical product. With most included
      studies carried out to support a market launch, the dominant methodology was
      early health economic modeling. Further methodological development is required,
      in particular, by combining systems engineering and health economics to manage
      uncertainty in medical product portfolios.

PMID- 28432643
TI  - Out-of-Pocket Payments and Subjective Unmet Need of Healthcare.
AB  - We present a critical review of the literature that discusses the link between
      the level of out-of-pocket payments in developed countries and the share of
      people in these countries reporting that they postpone or forgo healthcare for
      financial reasons. We discuss the pros and cons of measuring access problems with
      this subjective variable. Whereas the quantitative findings in terms of numbers
      of people postponing care must be interpreted with utmost caution, the picture
      for the vulnerable groups in society is reasonably robust and unsurprising:
      people with low incomes and high morbidity and incomplete (or non-existent)
      insurance coverage are most likely to postpone or forgo healthcare for financial
      reasons. It is more surprising that people with high incomes and generous
      insurance coverage also report that they postpone care. We focus on some policy
      relevant issues that call for further research: the subtle interactions between
      financial and non-financial factors, the possibility of differentiation of out-of
      pocket payments between patients and between healthcare services, and the
      normative debate around accessibility and affordability.

PMID- 28432644
TI  - Clinical Governance in Italy: 'Made in England' for Import?

PMID- 28432645
TI  - Efficacy of Lomitapide in the Treatment of Familial Homozygous
      Hypercholesterolemia: Results of a Real-World Clinical Experience in Italy.
AB  - INTRODUCTION: Homozygous familial hypercholesterolaemia (HoFH) is a rare form of
      inherited dyslipidemia resistant to conventional cholesterol-lowering medications
      so that lipoprotein apheresis (LA) is usually required. Lomitapide has been
      approved for the treatment of HoFH. The aim of this study was to evaluate the
      benefits of lomitapide in HoFH patients followed with the usual clinical care.
      METHODS: Clinical and biochemical data were retrospectively collected in 15 HoFH
      patients (10 with mutations in the LDLR gene and 5 in the LDLRAP1 gene) treated
      for at least 6 months with lomitapide in addition to lipid-lowering therapies
      (LLT) in different Lipid Clinics across Italy. RESULTS: The mean follow-up period
      was 32.3 +/- 29.7 months. During background therapies, HoFH patients showed a
      mean LDL-C level of 426.0 +/- 204.0 mg/dl. The addition of lomitapide at the
      average dosage of 19 mg/day lowered LDL-C levels by 68.2 +/- 24.8%. At their last
      visit, 60% of patients showed LDL-C <100 mg/dl and 46.6% <70 mg/dl. During follow
      up, 8 of 10 patients receiving LA (80%) stopped this treatment due to marked LDL
      C reduction. A wide range (13-95%) of individual LDL-C reduction was observed,
      but this was not related to genotype. During follow-up, 53.3% of patients
      reported at least one episode of diarrhea, but none was referred as severe; none
      had liver transaminase >5* ULN or had to stop treatment due to side effects. A
      subset of patients was evaluated by liver ultrasound and fibroscan (n = 5) or
      nuclear magnetic resonance with spectroscopy (MRS) (n = 1) not showing clinical
      evidence of liver damage. CONCLUSION: In this real-world experience, lomitapide
      was confirmed to be a very powerful cholesterol-lowering agent in HoFH showing a
      good safety profile.

PMID- 28432646
TI  - Is There a Role for Ivabradine in the Contemporary Management of Patients with
      Chronic Heart Failure in Academic and Community Heart Failure Clinics in Canada?
AB  - INTRODUCTION: In patients with heart failure (HF) and reduced ejection fraction,
      increased heart rate (HR) is an independent risk factor for adverse outcomes. In
      systolic HF treatment with the If inhibitor ivabradine trial (SHIFT), Ivabradine
      improved survival when added to conventional treatment including beta-blockers.
      However, the extent of benefit in the real world is unclear. We examined the
      characteristics of patients on guideline-directed therapy and determined who had
      SHIFT-like characteristics. METHODS: A total of 1096 patients with chronic HF
      were reviewed from June 2014 to April 2015 in two HF clinics in Toronto: an
      academic institution (AI), and a community hospital (CH) clinic. SHIFT-like
      characteristics [left ventricular ejection fraction (LVEF) <=35%; sinus rhythm;
      and HR >= 70 bpm] were described. RESULTS: For all patients, mean age was 75 +/-
      13 years, overall LVEF was 44 +/- 15%, AI less than CH (41.9 +/- 14.0% vs. 45.7
      +/- 15.0%; p < 0.0001). More than two-thirds of patients in both groups were on
      beta-blockers; with less than one-third at target dose. The proportion of
      patients with SHIFT-like characteristics was 8.4% AI and 11.7% CH, respectively
      (p = 0.0658). CONCLUSION: In HF clinics from both academic and community
      hospitals in Toronto, up-titration in the dose of beta-blockers and other
      guideline therapy can be improved on. A small proportion of patients with HF and
      SHIFT-like characteristics may potentially benefit from the addition of
      Ivabradine, just approved in Canada; this number will be further reduced if
      target dosage for beta-blockers is achieved. FUNDING: Servier Inc.

PMID- 28432648
TI  - Rationale for New Checkpoint Inhibitor Combinations in Melanoma Therapy.
AB  - The use of monoclonal antibodies that block immunologic checkpoints, which
      mediate adaptive immune resistance, has revolutionized the treatment of
      metastatic melanoma patients. Specifically, targeting single immune suppressive
      molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or
      programmed cell death protein 1 (PD-1) expressed on T cells or its primary
      ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical
      benefit for a subset of melanoma patients. Although single-agent immune
      checkpoint inhibitor therapy has demonstrated promising clinical activity in
      metastatic melanoma patients, there is still a significant proportion of patients
      who show primary resistance to these therapies. Increased clinical efficacy was
      reported in phase II and III randomized studies by co-targeting CTLA-4 and PD-1
      in the treatment of advanced melanoma, indicating the existence of multiple non
      redundant immunosuppressive pathways in the tumor microenvironment. Nevertheless,
      only 50% of patients responded to combined anti-CTLA-4 and anti-PD-1 treatment.
      Additionally, the combination regimen was associated with severe toxicity in >50
      60% of patients. In this review we summarize the rationale for new checkpoint
      inhibitor combinations in melanoma therapy and discuss how biologic-driven
      stratification enables the design of optimal combination therapies tailored to
      target different tumor microenvironments.

PMID- 28432649
TI  - Psoriasis, Depression, and Inflammatory Overlap: A Review.
AB  - Psoriasis has an enormous impact on patients' lives and is frequently associated
      with depression. Depression in psoriasis may be attributed, at least in part, to
      elevated proinflammatory cytokines rather than the psychosocial impact of
      psoriasis itself. Biologics that target inflammatory cytokines treat the clinical
      manifestations of psoriasis, but may also play a role in reducing associated
      depression. Multiple biologics have decreased symptoms of depression during
      clinical trials in psoriasis; however, these studies used a variety of depression
      screening tools, which limits comparison. Furthermore, it is difficult to
      distinguish whether improved depression is the result of the direct anti
      inflammatory effect of the biologic, or the indirect effect of improved psoriasis
      leading to better psychological status. Future studies evaluating depression in
      patients with psoriasis could benefit from a standardized depression screening
      tool to mitigate discrepancies and facilitate comparison across treatment types.
      Here, we highlight the inflammatory overlap between psoriasis and depression by
      examining the pathophysiology of depression, and reviewing psoriasis clinical
      studies that assessed depression as an outcome measure.

PMID- 28432647
TI  - The GENDER ATTENTION Observational Study: Gender and Hormonal Status Differences
      in the Incidence of Adverse Events During Cyclosporine Treatment in Psoriatic
      Patients.
AB  - INTRODUCTION: Female sex has been shown to be a risk factor for the development
      of adverse drug reactions; however, this has not been studied for cyclosporine
      (CsA). The aim of this study was to investigate, in Italian dermatological
      practice, the influence of gender and menopause and related hormones on the
      incidence of adverse events (AEs) during CsA treatment in psoriatic patients.
      METHODS: Multicenter, prospective, observational study conducted from May 2011 to
      June 2013. Patients with plaque psoriasis, undergoing a new CsA administration
      course, or about to start it, were enrolled in the outpatient clinics of Italian
      dermatological centers. During the 2-6 months of study duration, patients had to
      note all AEs that occurred in a diary that was reviewed by the investigators at
      the follow-up visit. Sex hormone levels were measured within 7 days from the
      start date of a menstrual cycle. RESULTS: A total of 969 adult psoriatic patients
      were enrolled in the study, divided into four cohorts: fertile women and
      corresponding age-matched men; postmenopausal women and corresponding age-matched
      men. A significant difference in the percentage of patients with AEs was observed
      between fertile and postmenopausal women, but not between women and age-matched
      men. AE incidence rate was about 37% higher in fertile women than in age-matched
      men and about 18% higher in postmenopausal women than in age-matched men, but
      differences were not statistically significant. Incidence rate ratio of fertile
      vs. postmenopausal women was 0.67, reaching statistical significance. AEs were
      mild or moderate in severity in the great majority of patients of all cohorts and
      postmenopausal women had significantly less grade 1-2 AEs compared to fertile
      women, but more grade 3-4 AEs. FSH levels were significantly higher in
      postmenopausal women reporting no AEs, and DHEA sulfate levels were about 10%
      higher in men with no AEs, compared to those reporting at least one AE. Cortisol
      levels were slightly though significantly higher in postmenopausal women with no
      AE. CONCLUSIONS: A better understanding of sex- and hormone-related influences on
      drug responses may help to improve drug safety and efficacy, by permitting one to
      tailor pharmacological treatments to individual subjects or defined patient
      cohorts. FUNDING: Novartis Farma S.p.A., Italy.

PMID- 28432650
TI  - Efficacy and Tolerability of a 2-Year Rituximab Maintenance Therapy in Patients
      with Advanced Follicular Lymphoma after Induction of Response with Rituximab
      Containing First Line-Regimens (HUSOM Study).
AB  - Follicular lymphoma is a lymphoid malignancy commonly showing slow progression
      which makes the treatment of the disease challenging. Rituximab monotherapy and
      rituximab added to standard chemotherapy has been proven to increase survival
      among patients with advanced stage of the disease. However, the benefit of a
      rituximab maintenance therapy after induction was still unclear at the time of
      the initiation of this study. HUSOM was a phase III open-label, single-arm, multi
      centre study aimed to assess the efficacy and the safety of the 12 cycles of
      rituximab (375 mg/m2 every 8 weeks) maintenance therapy in patients had already
      presented partial or complete response to R-CVP or R-CHOP. Efficacy endpoints
      such as event-free survival and overall survival were estimated. Adverse events
      were recorded during the entire course of the study. A total number of 124
      patients were enrolled by 15 Hungarian study sites. Out of these, 86 patients
      received 12 cycles of rituximab and 69 patients completed the 3-year follow-up
      phase as well. The probabilities of the event free survival and progression at
      4.3 years were estimated to be 70.3% and 74.4%, respectively. The overall and the
      disease free survival at 4 years were estimated to be 90.7% and 87.9%,
      respectively. A total number of 85 adverse events were reported during the study
      out of which 5 AEs were considered to be related to the administration of
      rituximab. Analyses of the efficacy variables have revealed comparable results to
      those reported by controlled clinical trials (EORTC 20981, PRIMA) conducted in
      parallel with the HUSOM study.

PMID- 28432651
TI  - cR and pR: The Residual Tumor Classification Revisited.

PMID- 28432652
TI  - Blood ties and trust: a comparative history of policy on family consent in Japan
      and the United States.
AB  - Informed consent honors the autonomous decisions of patients, and family consent
      places importance on decisions made by their families. However, there is little
      understanding of the relationship between these two medical decision-making
      approaches. Both approaches exist in Japan as part of its truth disclosure
      policy. What is the status of family consent in the United States, from which
      Japan introduced informed consent? This paper compares the situation in the
      United States with that in Japan, where family consent has been combined with
      informed consent. It then explains the history of policy development through
      which family consent was added to informed consent in the United States. Based on
      this analysis, the paper suggests that the relationship between informed consent
      and family consent in the United States was established on the basis of a family
      model that places more importance on trust-based relationships than it does on
      blood ties.

PMID- 28432653
TI  - Analyzing Glycopeptide Isomers by Combining Differential Mobility Spectrometry
      with Electron- and Collision-Based Tandem Mass Spectrometry.
AB  - Differential mobility spectrometry (DMS) has been employed to separate isomeric
      species in several studies. Under the right conditions, factors such as
      separation voltage, temperature, the presence of chemical modifiers, and
      residence time can combine to provide unique signal channels for isomeric
      species. In this study, we examined a set of glycopeptide isomers, MUC5AC-3 and
      MUC5AC-13, which bear an N-acetyl-galactosamine (GalNAc) group on either
      threonine-3 or threonine-13. When analyzed as a mixture, the resulting MS and
      MS/MS spectra yield fragmentation patterns that cannot discern these convolved
      species. However, when DMS is implemented during the analysis of this mixture,
      two features emerge in the DMS ionogram representing the two glycopeptide
      isomers. In addition, by locking in DMS parameters at each feature, we could
      observe several low intensity CID fragments that contain the GalNAc functionality
      specific amino acid residues - identifying the DMS separation of each isomer
      without standards. Besides conventional CID MS/MS, we also implemented electron
      capture dissociation (ECD) after DMS separation, and clearly resolved both
      isomers with this fragmentation method, as well. The electron energy used in
      these ECD experiments could be tuned to obtain maximum sequence coverage for
      these glycopeptides; this was critical as these ions were present as doubly
      protonated species, which are much more difficult to fragment efficiently via
      electron-transfer dissociation (ETD). Overall, the combination of DMS with
      electron- or collision-based MS/MS methods provided enhanced separation and
      sequence coverage for these glycopeptide isomers. Graphical Abstract ?.

PMID- 28432654
TI  - Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from
      Rat Brain Tissue Implanted with Silver Nanoparticles.
AB  - Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate
      (AgNP) matrix generates reproducible imaging of lipids in rodent models of
      disease and injury. Gas-phase production and acceleration of size-selected 8 nm
      AgNP is followed by controlled ion beam rastering and soft landing implantation
      of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality
      images for most lipid classes in rat brain tissue (in positive mode:
      galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl
      ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides,
      sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in
      serial sections of brain tissue is achieved within <10% tolerance by selecting
      argentated instead of alkali cationized ions. The imaging of brain tissues
      spotted with pure standards was used to demonstrate that Ag cationized ceramide
      and diacylglycerol ions are from intact, endogenous species. In contrast, almost
      all Ag cationized fatty acid ions are a result of fragmentations of numerous
      lipid types having the fatty acid as a subunit. Almost no argentated intact fatty
      acid ions come from the pure fatty acid standard on tissue. Graphical Abstract ?.

PMID- 28432655
TI  - Direct Analysis of Organic Compounds in Liquid Using a Miniature Photoionization
      Ion Trap Mass Spectrometer with Pulsed Carrier-Gas Capillary Inlet.
AB  - A miniature ion trap mass spectrometer with capillary direct sampling and vacuum
      ultraviolet photoionization source was developed to conduct trace analysis of
      organic compounds in liquids. Self-aspiration sampling is available where the
      samples are drawn into the vacuum chamber through a capillary with an extremely
      low flow rate (less than 1 MUL/min), which minimizes sample consumption in each
      analysis to tens of micrograms. A pulsed gas-assisted inlet was designed and
      optimized to promote sample transmission in the tube and facilitate the cooling
      of ions, thereby improving instrument sensitivity. A limit of detection of 2 ppb
      could be achieved for 2,4-dimethylaniline in a methanol solution. The sampling
      system described in the present study is specifically suitable for a miniature
      photoionization ion trap mass spectrometer that can perform rapid and online
      analysis for liquid samples. Graphical Abstract ?.

PMID- 28432656
TI  - Collisional Cross-Sections with T-Wave Ion Mobility Spectrometry without
      Experimental Calibration.
AB  - A method for relating traveling-wave ion mobility spectrometry (TWIMS) drift
      times with collisional cross-sections using computational simulations is
      presented. This method is developed using SIMION modeling of the TWIMS potential
      wave and equations that describe the velocity of ions in gases induced by
      electric fields. The accuracy of this method is assessed by comparing the
      collisional cross-sections of 70 different reference ions obtained using this
      method with those obtained from static drift tube ion mobility measurements. The
      cross-sections obtained here with low wave velocities are very similar to those
      obtained using static drift (average difference = 0.3%) for ions formed from both
      denaturing and buffered aqueous solutions. In contrast, the cross-sections
      obtained with high wave velocities are significantly greater, especially for ions
      formed from buffered aqueous solutions. These higher cross-sections at high wave
      velocities may result from high-order factors not accounted for in the model
      presented here or from the protein ions unfolding during TWIMS. Results from this
      study demonstrate that collisional cross-sections can be obtained from single
      TWIMS drift time measurements, but that low wave velocities and gentle instrument
      conditions should be used in order to minimize any uncertainties resulting from
      high-order effects not accounted for in the present model and from any protein
      unfolding that might occur. Thus, the method presented here eliminates the need
      to calibrate TWIMS drift times with collisional cross-sections measured using
      other ion mobility devices. Graphical Abstract ?.

PMID- 28432658
TI  - Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular
      Disease?
AB  - PURPOSE OF REVIEW: Omega-3 fatty acids are increasingly used for the protection
      of cardiovascular disease. The main but not the sole mechanism of action is the
      reduction of triglyceride levels. In this review, we summarize the effect of
      omega-3 supplements on all-cause and cardiovascular mortality, myocardial
      infarction, and stroke from the relevant randomized controlled trials. RECENT
      FINDINGS: Twenty-one randomized controlled trials assessed omega-3
      supplementation on mortality and cardiovascular-related outcomes. From these
      studies, as well as from the relevant meta-analyses, we found that omega-3
      supplements do not exert a consistent benefit for cardiovascular protection.
      There is uncertainty of a clear profit from omega-3 supplementation in
      cardiovascular disease.

PMID- 28432657
TI  - In vitro assay for measuring real time topotecan release from liposomes: release
      kinetics and cellular internalization.
AB  - Topotecan is a drug that is under investigation for the treatment of
      neuroblastoma and has been encapsulated into liposomes to improve its therapeutic
      efficacy. However, liposomal formulations still need to be optimized for drug
      retention and new techniques to measure drug release are required to better
      understand this process. Here, a novel in vitro method based on fluorescence de
      quenching and an automated microscopy imaging platform were developed for
      monitoring, in real time, the release of topotecan from a liposomal formulation.
      Drug release from liposomes was monitored for up to 15 h under different
      conditions including topotecan concentrations, fetal bovine serum amounts (0
      20%), and temperatures (25 and 37  degrees C). A cell-based assay was used to
      assess liposome association with cells in culture and to quantify amounts of
      topotecan internalized into cells after release from liposomes. Our results show
      that the liposomal topotecan concentration had an influence on drug release
      kinetics: there was a reduction in release rate as a function of increasing
      concentration. Our data also show that topotecan release from the liposomal
      formulation was dependent on serum concentration where faster release was
      observed at higher serum concentrations, and on temperature where faster release
      was found at 37  degrees C. This real-time liposomal drug release assay allows
      for better understanding of the factors important in governing release of
      topotecan. The assay will be essential towards designing liposomal formulations
      of topotecan (and potentially of other camptothecin derivatives such as
      irinotecan) with optimized retention times and better therapeutic efficacy for
      testing in the clinic.

PMID- 28432660
TI  - Management of Dyslipidemias in Europe and the USA: Same Evidence, Different
      Conclusions? Can We Find Common Ground?
AB  - PURPOSE OF REVIEW: An examination of the current ACC/AHA and ESC/EAS Guidelines
      on the management of dyslipidemias for common ground and differences. RECENT
      FINDINGS: There is much common ground. Both note that ASCVD is, in most people,
      the product of a number of risk factors, notably tobacco exposure,
      hyperlipidemia, hypertension, inactivity, overweight and diabetes. They stress
      that risk calculators can help in the assessment of risk in apparently healthy
      persons. Persons with established ASCVD and many with diabetes or renal
      impairment are at high to very high risk and warrant intensive risk factor
      advice. The ACC/AHA Guidelines favor the universal use of statins in all high
      risk subjects. In contrast, the ESC/EAS Guidelines favor a goal approach based on
      total risk and baseline LDL cholesterol level. Perhaps the most important
      challenges are to stress similarities rather than differences and to simplify
      communications with both healthcare professionals and the public. Subjects with
      established vascular disease and renal impairment and many with diabetes are at
      high to very high risk and need intensive risk factor management. A risk chart or
      calculator is recommended to assess total risk in apparently healthy persons. The
      higher the risk, the more intense the risk factor management.

PMID- 28432659
TI  - Current Role of Blood and Urine Biomarkers in the Clinical Care of Adults with
      Congenital Heart Disease.
AB  - PURPOSE OF REVIEW: There is an increasing number of adult patients with
      congenital heart disease (CHD). While several biomarkers have been validated and
      integrated into general cardiology clinical practice, these tests are often
      applied to adults with CHD in the absence of disease-specific validation.
      Although these patients are often grouped into a single population, there is
      heterogeneous pathophysiology, variable disease chronicity, extensive multisystem
      involvement, and a low event rate relative to acquired heart disease. These stand
      as challenges to systematic investigation and clinical application of biomarkers
      for adults with CHD. This paper reviews recent studies investigating the use of
      biomarkers in this population, with emphasis on biomarkers applied in clinical
      adult CHD care. RECENT FINDINGS: A handful of biomarkers have been integrated
      into adult CHD practice, such as iron studies in cyanotic heart disease and stool
      alpha-1 antitrypsin for diagnosis of protein losing enteropathy in the Fontan
      circulation. Use of kidney and liver tests has been studied in prognostication of
      adult CHD patients. A few other biomarkers like natriuretic peptides and
      troponins seem likely to provide useful information in other ACHD situations
      based on limited disease-specific data and extrapolation from acquired heart
      disease. More research is needed to support the robust validity of most existing
      clinical biomarkers in adult congenital cardiology practice. Until data from
      larger, prospectively enrolled cohorts are available, clinical use of biomarkers
      in these patients will require careful interpretation with attention to
      underlying pathophysiology, as well as detailed understanding of potential
      pitfalls of specific assays and clinical contexts.

PMID- 28432661
TI  - Lipid Biomarkers for Risk Assessment in Acute Coronary Syndromes.
AB  - PURPOSE OF REVIEW: The objective of this review was to summarize evidence
      gathered for the prognostic value of routine and novel blood lipids and
      lipoproteins measured in patients with acute coronary syndromes (ACS). RECENT
      FINDINGS: Data supports clear association with risk and actionable value for non
      high-density lipoprotein (Non-HDL) cholesterol and plasma ceramides in a setting
      of ACS. The prognostic value and clinical actionability of apolipoprotein B
      (apoB) and lipoprotein(a) [Lp(a)] in ACS have not been thoroughly tested, while
      the data for omega-3 fatty acids and oxidized low-density lipoprotein (Ox-LDL)
      are either untested or more varied. Measuring basic lipids, which should include
      Non-HDL cholesterol, at the time of presentation for ACS is guideline mandated.
      Plasma ceramides also provide useful information to guide both treatment
      decisions and follow-up. Additional studies targeting ACS patients are necessary
      for apoB, Lp(a), omega-3 fatty acids, and Ox-LDL.

PMID- 28432662
TI  - Targeting LDL Cholesterol: Beyond Absolute Goals Toward Personalized Risk.
AB  - PURPOSE OF REVIEW: The aim of this study was to review and assess the evidence
      for low-density lipoprotein cholesterol (LDL-C) treatment goals as presented in
      current guidelines for primary and secondary prevention of cardiovascular
      disease. RECENT FINDINGS: Different sets of guidelines and clinical studies for
      secondary prevention have centered on lower absolute LDL-C targets [<70 mg/dL
      (<1.8 mmol/L)], greater percent reductions of LDL-C (>=50%), or more intense
      treatment to achieve greater reductions in cardiovascular risk. Population-based
      risk models serve as the basis for statin initiation in primary prevention.
      Reviews of current population risk models for primary prevention show moderate
      ability to discriminate [with c-statistics ranging from 0.67 to 0.77 (95% CIs
      from 0.62 to 0.83) for men and women] with poor calibration and overestimation of
      risk. Individual clinical trial data are not compelling to support specific LDL-C
      targets and percent reductions in secondary prevention. Increasing utilization of
      electronic health records and data analytics will enable the development of
      individualized treatment goals in both primary and secondary prevention.

PMID- 28432663
TI  - The Vascular Wall: a Plastic Hub of Activity in Cardiovascular Homeostasis and
      Disease.
AB  - PURPOSE OF REVIEW: This review aims to summarize recent findings regarding the
      plasticity and fate switching among somatic and progenitor cells residing in the
      vascular wall of blood vessels in health and disease. RECENT FINDINGS: Cell
      lineage tracing methods have identified multiple origins of stem cells,
      macrophages, and matrix-producing cells that become mobilized after acute or
      chronic injury of cardiovascular tissues. These studies also revealed that in the
      disease environment, resident somatic cells become plastic, thereby changing
      their stereotypical identities to adopt proinflammatory and profibrotic
      phenotypes. Currently, the functional significance of this heterogeneity among
      reparative cells is unknown. Furthermore, mechanisms that control cellular
      plasticity and fate decisions in the disease environment are poorly understood.
      Cardiovascular diseases are responsible for the majority of deaths worldwide.
      From a therapeutic perspective, these novel discoveries may identify new targets
      to improve the repair and regeneration of the cardiovascular system.

PMID- 28432664
TI  - Human perinatal immunity in physiological conditions and during infection.
AB  - The intrauterine environment was long considered sterile. However, several
      infectious threats are already present during fetal life. This review focuses on
      the postnatal immunological consequences of prenatal exposure to microorganisms
      and related inflammatory stimuli. Both the innate and adaptive immune systems of
      the fetus and neonate are immature, which makes them highly susceptible to
      infections. There is good evidence that prenatal infections are a primary cause
      of preterm births. Additionally, the association between antenatal inflammation
      and adverse neonatal outcomes has been well established. The lung,
      gastrointestinal tract, and skin are exposed to amniotic fluid during pregnancy
      and are probable targets of infection and subsequent inflammation during
      pregnancy. We found a large number of studies focusing on prenatal infection and
      the host response. Intrauterine infection and fetal immune responses are well
      studied, and we describe clinical data on cellular, cytokine, and humoral
      responses to different microbial challenges. The link to postnatal immunological
      effects including immune paralysis and/or excessive immune activation, however,
      turned out to be much more complicated. We found studies relating prenatal
      infectious or inflammatory hits to well-known neonatal diseases such as
      respiratory distress syndrome, bronchopulmonary dysplasia, and necrotizing
      enterocolitis. Despite these data, a direct link between prenatal hits and
      postnatal immunological outcome could not be undisputedly established. We did
      however identify several unresolved topics and propose questions for further
      research.

PMID- 28432665
TI  - Systemic and microcirculatory effects of blood transfusion in experimental
      hemorrhagic shock.
AB  - BACKGROUND: The microvascular reperfusion injury after retransfusion has not been
      completely characterized. Specifically, the question of heterogeneity among
      different microvascular beds needs to be addressed. In addition, the
      identification of anaerobic metabolism is elusive. The venoarterial PCO2 to
      arteriovenous oxygen content difference ratio (Pv-aCO2/Ca-vO2) might be a
      surrogate for respiratory quotient, but this has not been validated. Therefore,
      our goal was to characterize sublingual and intestinal (mucosal and serosal)
      microvascular injury after blood resuscitation in hemorrhagic shock and its
      relation with O2 and CO2 metabolism. METHODS: Anesthetized and mechanically
      ventilated sheep were assigned to stepwise bleeding and blood retransfusion (n =
      10) and sham (n = 7) groups. We performed analysis of expired gases, arterial and
      mixed venous blood gases, and intestinal and sublingual videomicroscopy. RESULTS:
      In the bleeding group during the last step of hemorrhage, and compared to the
      sham group, there were decreases in oxygen consumption (3.7 [2.8-4.6] vs. 6.8
      [5.8-8.0] mL min-1 kg-1, P < 0.001) and increases in respiratory quotient (0.96
      [0.91-1.06] vs. 0.72 [0.69-0.77], P < 0.001). Retransfusion normalized these
      variables. The Pv-aCO2/Ca-vO2 increased in the last step of bleeding (2.4 [2.0
      2.8] vs. 1.1 [1.0-1.3], P < 0.001) and remained elevated after retransfusion,
      compared to the sham group (1.8 [1.5-2.0] vs. 1.1 [0.9-1.3], P < 0.001). Pv
      aCO2/Ca-vO2 had a weak correlation with respiratory quotient (Spearman R = 0.42,
      P < 0.001). All the intestinal and sublingual microcirculatory variables were
      affected during hemorrhage and improved after retransfusion. The recovery was
      only complete for intestinal red blood cell velocity and sublingual total and
      perfused vascular densities. CONCLUSIONS: Although there were some minor
      differences, intestinal and sublingual microcirculation behaved similarly.
      Therefore, sublingual mucosa might be an adequate window to track intestinal
      microvascular reperfusion injury. Additionally, Pv-aCO2/Ca-vO2 was poorly
      correlated with respiratory quotient, and its physiologic behavior was different.
      Thus, it might be a misleading surrogate for anaerobic metabolism.

PMID- 28432666
TI  - Optimizing myocardial metabolism for fluorine-18 fluorodeoxyglucose positron
      emission tomography imaging of cardiac inflammation.

PMID- 28432667
TI  - Fully automated analysis of perfusion data: The rise of the machines.

PMID- 28432668
TI  - Comparison of ESC and ACC/AHA guidelines for myocardial revascularization: are
      the differences clinically relevant? The European perspective.

PMID- 28432669
TI  - Advances in dual respiratory and ECG-gated SPECT imaging.

PMID- 28432670
TI  - The complementary nature of tissue Doppler to 99mTc-PYP imaging in diagnosis of
      right ventricular cardiac amyloidosis.

PMID- 28432671
TI  - Investigation of the physical effects of respiratory motion compensation in a
      large population of patients undergoing Tc-99m cardiac perfusion SPECT/CT stress
      imaging.
AB  - BACKGROUND: Respiratory motion can deteriorate image fidelity in cardiac
      perfusion SPECT. We determined the extent of respiratory motion, assessed its
      impact on image fidelity, and investigated the existence of gender differences,
      thereby examining the influence of respiratory motion in a large population of
      patients. METHODS: One thousand one hundred and three SPECT/CT patients underwent
      visual tracking of markers on their anterior surface during stress acquisition to
      track respiratory motion. The extent of motion was estimated by registration.
      Visual indicators of changes in cardiac slices with motion correction, and the
      correlation between the extent of motion with changes in segmental-counts were
      assessed. RESULTS: Respiratory motion in the head-to-feet direction was the
      largest component of motion, varying between 1.1 and 37.4 mm, and was
      statistically significantly higher (p = 0.002) for males than females. In 33.0%
      of the patients, motion estimates were larger than 10 mm. Patients progressively
      show more distinct visual changes with an increase in the extent of motion. The
      increase in segmental-count differences in the anterior, antero-lateral, and
      inferior segments correlated with the extent of motion. CONCLUSIONS: Respiratory
      motion correction diminished the artefactual reduction in anterior and inferior
      wall counts associated with respiratory motion. The extent of improvement was
      strongly related to the magnitude of motion.

PMID- 28432672
TI  - Para-atrial non-acute mediastinal hematoma after left atrial maze procedure
      mimicking tumor in a patient with treated melanoma.
AB  - INTRODUCTION: The Cox Maze III procedure is considered the gold standard open
      surgical procedure for management of atrial fibrillation. This article outlines a
      unique case of a para-atrial mediastinal hematoma following a bilateral
      thoracoscopic left atrial Maze procedure mimicking malignancy. REPORT: A 60-year
      old male, with past history of melanoma, underwent bilateral thoracoscopic left
      atrial mini maze procedure with radiofrequency energy and exclusion of the left
      atrial appendage. Seven months later, a chest computed tomography (CT) scan was
      performed to evaluate for pulmonary embolism. The CT scan unexpectedly showed an
      ill-defined, heterogeneous para-atrial mass immediately superior to the left
      atrium concerning for tumor and mediastinal adenopathy. The mass was moderately
      hypermetabolic on subsequent 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)
      positron emission tomography (PET) scan. A follow-up PET/CT three months later
      demonstrated near-complete resolution of the para-atrial mass with minimal
      residual hematoma. CONCLUSION: Non-acute mediastinal hematoma following a maze
      procedure can potentially be confused with a tumor mass and/or lymphadenopathy on
      CT and FDG PET/CT. With knowledge of the potential for false-positive FDG uptake
      in a hematoma, the lesion was monitored, and unnecessary biopsy was avoided.

PMID- 28432673
TI  - Prognostic value of left ventricular dyssynchrony evaluated by gated myocardial
      perfusion imaging in patients with chronic kidney disease and normal perfusion
      defect scores.
AB  - BACKGROUND: This study aimed to investigate whether indices of left ventricular
      (LV) dyssynchrony by gated myocardial perfusion SPECT (GMPS) could be useful to
      predict prognosis in chronic kidney disease (CKD) patients with normal perfusion
      defect scores. METHODS: One hundred and sixty-seven CKD patients with normal
      perfusion defect scores on adenosine-stress 201Tl GMPS and no previous history of
      overt heart diseases were enrolled. Phase standard deviation (PSD) and bandwidth
      (BW) were automatically calculated from GMPS. The major adverse cardiac events
      (MACEs) for a mean of 560 days were defined as sudden cardiac death, fatal
      arrhythmias, and acute coronary syndrome requiring urgent coronary
      revascularization. Patients were divided into two groups according to the
      presence or absence of MACEs. RESULTS: The MACEs occurred in 12 patients (7.1%).
      Patients who experienced MACEs showed significantly higher PSD and wider BW than
      those who did not. In the Kaplan-Meier event-free survival analysis, cardiac
      event rate was significantly higher in the high-PSD and wide-BW group (n = 81)
      than in the low-PSD and narrow-BW group (n = 71) (P = .002). The multivariate
      regression analysis revealed that the PSD was associated with MACEs (odds ratio
      1.33, 95% confidence interval 1.05-1.69, P = .01). CONCLUSION: The LV
      dyssynchrony indices from GMPS may be novel prognostic predictors in CKD patients
      with normal perfusion defect scores.

PMID- 28432674
TI  - Partial volume correction of brain PET studies using iterative deconvolution in
      combination with HYPR denoising.
AB  - BACKGROUND: Accurate quantification of PET studies depends on the spatial
      resolution of the PET data. The commonly limited PET resolution results in
      partial volume effects (PVE). Iterative deconvolution methods (IDM) have been
      proposed as a means to correct for PVE. IDM improves spatial resolution of PET
      studies without the need for structural information (e.g. MR scans). On the other
      hand, deconvolution also increases noise, which results in lower signal-to-noise
      ratios (SNR). The aim of this study was to implement IDM in combination with
      HighlY constrained back-PRojection (HYPR) denoising to mitigate poor SNR
      properties of conventional IDM. METHODS: An anthropomorphic Hoffman brain phantom
      was filled with an [18F]FDG solution of ~25 kBq mL-1 and scanned for 30 min on a
      Philips Ingenuity TF PET/CT scanner (Philips, Cleveland, USA) using a dynamic
      brain protocol with various frame durations ranging from 10 to 300 s. Van Cittert
      IDM was used for PVC of the scans. In addition, HYPR was used to improve SNR of
      the dynamic PET images, applying it both before and/or after IDM. The Hoffman
      phantom dataset was used to optimise IDM parameters (number of iterations, type
      of algorithm, with/without HYPR) and the order of HYPR implementation based on
      the best average agreement of measured and actual activity concentrations in the
      regions. Next, dynamic [11C]flumazenil (five healthy subjects) and [11C]PIB (four
      healthy subjects and four patients with Alzheimer's disease) scans were used to
      assess the impact of IDM with and without HYPR on plasma input-derived
      distribution volumes (V T) across various regions of the brain. RESULTS: In the
      case of [11C]flumazenil scans, Hypr-IDM-Hypr showed an increase of 5 to 20% in
      the regional V T whereas a 0 to 10% increase or decrease was seen in the case of
      [11C]PIB depending on the volume of interest or type of subject (healthy or
      patient). References for these comparisons were the V Ts from the PVE-uncorrected
      scans. CONCLUSIONS: IDM improved quantitative accuracy of measured activity
      concentrations. Moreover, the use of IDM in combination with HYPR (Hypr-IDM-Hypr)
      was able to correct for PVE without increasing noise.

PMID- 28432675
TI  - Transoral thyroidectomy: advantages and limitations.
AB  - In this opinion paper of the Journal of Endocrinological Investigation, leading
      experts in the field report on their current clinical experience with a novel
      approach for thyroid gland surgery, namely, "transoral thyroidectomy" (TOT). This
      feasible and novel surgical procedure does not require visible incisions and is,
      therefore, a truly scarless surgery. Patients meeting the following criteria can
      be considered as candidates for TOT: (a) an ultrasonographically (US) estimated
      thyroid diameter <=10 cm; (b) US-estimated gland volume <=45 mL; (c) nodule size
      <=50 mm; (d) presence of a benign tumor such as a thyroid cyst or a single- or
      multi-nodular goiter; (e) Bethesda 3 and/or 4 category and (f) papillary
      microcarcinoma without the evidence of metastasis. The procedure is conducted via
      a three-port technique at the oral vestibule using a 10-mm port for the 30
      degrees  endoscope and two additional 5-mm ports for the dissecting and
      coagulating instruments. TOT is performed using conventional endoscopic
      instruments and is probably the best scarless approach to the thyroid because of
      the short distance between the thyroid and the incisions placed intra-orally that
      do not result in any cutaneous scar and upon following the surgical planes.
      Experts in TOT organized a working group of general, endocrine, head and neck ENT
      surgeons and endocrinologist to develop the standards for practicing this
      emerging technique.

PMID- 28432676
TI  - Bifidobacterium adolescentis (DSM 20083) and Lactobacillus casei (Lafti L26-DSL):
      Probiotics Able to Block the In Vitro Adherence of Rotavirus in MA104 Cells.
AB  - Rotavirus is the leading worldwide cause of gastroenteritis in children under
      five years of age. Even though there are some available vaccines to prevent the
      disease, there are limited strategies for challenging diarrhea induced by
      rotavirus infection. For this reason, researchers are constantly searching for
      other approaches to control diarrhea by means of probiotics. In order to
      demonstrate the ability of some probiotic bacteria to interfere with the in vitro
      rotavirus infection in MA104 cells, strains of Lactobacillus sp. and
      Bifidobacterium sp. were tested in MA104 cells before the viral infection. As a
      preliminary assay, a blocking effect treatment was performed with viable
      bacteria. In this screening assay, four of initial ten bacteria showed a slight
      reduction of the viral infection (measured by percentage of infection). L. casei
      (Lafti L26-DSL), L. fermentum(ATCC 9338), B. adolescentis (DSM 20083), and B.
      bifidum (ATCC 11863) were used in further experiments. Three different treatments
      were tested in order to evaluate protein-based metabolites obtained from
      mentioned bacteria: (i) cell exposure to the protein-based metabolites before
      viral infection, (ii) exposure to protein-based metabolites after viral
      infection, and (iii) co-incubation of the virus and protein-based metabolites
      before viral infection to the cell culture. The best effect performed by protein
      based metabolites was observed during the co-incubation assay of the virus and
      protein-based metabolites before adding them into the cell culture. The results
      showed 25 and 37% of infection in the presence of L. casei and B. adolescentis
      respectively. These results suggest that the antiviral effect may be occurring
      directly with the viral particle instead of making a blocking effect of the
      cellular receptors that are needed for the viral entrance.

PMID- 28432677
TI  - Development of Yoghurt with Jucara Pulp (Euterpe edulis M.) and the Probiotic
      Lactobacillus acidophilus La5.
AB  - Yoghurts are dairy products consumed worldwide and can be supplemented with
      substances that provide extra health benefits as well as probiotic strains. In
      this context, the present study aimed to prepare a yoghurt added of jucara
      (Euterpe edulis M.) pulp and the commercial probiotic strain Lactobacillus
      acidophilus La5. Moreover, the probiotic survival during storage and after in
      vitro exposure to simulated gastric and enteric conditions was evaluated. Four
      formulations of yoghurt were prepared: (a) natural yoghurt, (b) yoghurt added of
      probiotic, (c) yoghurt added of jucara pulp, and (d) yoghurt added of probiotic
      culture and jucara pulp. The preparations were evaluated for survival of
      probiotic strain during storage and its tolerance to gastric and enteric
      conditions in vitro. The probiotic population in yoghurt remained unchanged
      during 28 days of storage. In addition, jucara pulp increased the probiotic
      resistance to simulated gastric and enteric conditions in the first day of
      storage. These data indicate that jucara pulp is a potential ingredient for the
      production of probiotic yoghurts.

PMID- 28432678
TI  - Anal metastasis of rectal cancer-adenocarcinoma of squamous cells: a case report
      and literature review.
AB  - Anal metastasis of colorectal cancer is very rare and is usually associated with
      a history of anal disease, including anal fistula, fissure, hemorrhoidectomy, and
      anastomotic injury. We report a case of rectal cancer with a synchronous anal
      metastasis consisting of adenocarcinoma of squamous cells without a history of
      anal disease. A 60-year-old woman had a chief complaint of melena. She had a 1.5
      cm anal tumor on the perianal skin, and a Bollman type 2 rectal tumor on the Ra
      portion was found on colonoscopy. Biopsy of both tumors revealed a similar
      histology of well- to moderately differentiated adenocarcinoma. There was no sign
      of metastases in lymph nodes or other organs. For the purpose of diagnosis and
      treatment, transperineal local resection of the anal tumor was performed, and it
      was histologically identified as adenocarcinoma of squamous cells with no
      invasion to muscles, lymph ducts, or microvessels. The pathological margin was
      free. Then, to achieve radical cure, laparoscopic low anterior resection (LAR)
      with D3 lymphadenectomy was performed. The histological diagnosis of the anal
      tumor was adenocarcinoma of squamous cells without invasion to muscles, lymph
      ducts, or vessels. The surgical margin was completely free. Immunohistochemical
      analysis of both tumors revealed similar staining patterns, and the final
      diagnosis was rectal cancer with metastasis to the anal skin. The patient
      received no postoperative therapy, and no recurrences have been observed 12
      months after surgery. We expect that our sphincter-preserving surgical strategy
      provided a good prognosis for the synchronous rectal cancer and anal metastasis.
      This is a rare report of a case with an anal metastasis of colorectal cancer on
      perianal squamous cells without a history of anal disease that was resected while
      preserving anal function.

PMID- 28432679
TI  - Potential use of cowpea (Vigna unguiculata (L.) Walp.) stover treated with white
      rot fungi as rabbit feed.
AB  - BACKGROUND: Lignin inhibitory effects within the cell wall structure constitute a
      serious drawback in maximizing the utilization of fibrous feedstuffs in animal
      feeding. Therefore treatments that promote efficient delignification of these
      materials must be applied. This study evaluated the potential of white-rot fungi
      to upgrade the nutritive value of cowpea stover for rabbit feeding. RESULTS:
      There was an increase in the crude protein content of all substrates as a result
      of fungi treatments, reaching a net gain of 13% for Pleurotus citrinopileatus
      incubation. Overall, net losses of dry and organic matter occurred during fungi
      treatments. Although the fiber content remained identical, higher consumption of
      cell wall contents was measured for P. citrinopileatus incubation (between 40 and
      45%). The incubation period did not influence lignin degradation for any of the
      fungi treatments. Differences within the fungal degradation mechanisms indicate
      that P. citrinopileatus treatment was most effective, enhancing in vitro organic
      matter digestibility by around 30% compared with the control. CONCLUSION:
      Treatment of cowpea stover with P. citrinopileatus led to an efficient
      delignification process which resulted in higher in vitro organic matter
      digestibility, showing its potential in the nutritional valorization of this
      feedstuff. (c) 2017 Society of Chemical Industry.

PMID- 28432680
TI  - Longitudinal physical activity and sedentary behaviour in preschool-aged children
      with cerebral palsy across all functional levels.
AB  - AIM: To investigate longitudinal changes of habitual physical activity (HPA) and
      sedentary time in children with cerebral palsy (CP) aged 1 year 6 months to 5
      years across all functional abilities. METHOD: At study entry, 95 children (62
      males, 33 females) were classified using the Gross Motor Function Classification
      System (GMFCS) at levels I (50), II (9), III (16), IV (6), and V (14). Physical
      activity was recorded on a total of 159 occasions at four possible time points: 1
      year 6 months to 2 years; 2 years 6 months to 3 years; 4 years; and 5 years using
      ActiGraph for 3 days. Mixed-effects regression models were used for analyses.
      RESULTS: Participants classified at GMFCS levels I and II had stable HPA as they
      aged. HPA significantly decreased at 5 years in children classified at GMFCS
      levels III to V. Sedentary time significantly increased at 4 years and 5 years in
      all participants. Annual HPA significantly reduced in children classified at
      GMFCS levels III to V (-123 counts/min, 95% confidence interval [CI] -206 to -40)
      while annual sedentary time significantly increased in all participants (GMFCS
      levels I-II: 2.4%, 95% CI 0.7-4.1; GMFCS levels III-V: 6.9%, 95% CI 4.6-9.2).
      INTERPRETATION: Children with CP at all GMFCS levels should be encouraged to be
      physically active from early childhood as HPA levels start to decline from 4
      years. Breaks in sedentary time are required for all children with CP from the
      age of 3 years.

PMID- 28432681
TI  - Retrospective single center study of the efficacy of large spot 532 nm laser for
      the treatment of facial capillary malformations in 44 patients with the use of
      three-dimensional image analysis.
AB  - OBJECTIVE: We wanted to asses the efficacy of large spot 532 nm laser for the
      treatment of facial capillary malformations with the use of three-dimensional
      (3D) image analysis. STUDY DESIGN AND METHODS: Retrospective single center study
      on previously non-treated patients with facial capillary malformations (CM) was
      performed. A total of 44 consecutive Caucasian patients aged 5-66 were included.
      Patients had 3D photography performed before and after and had at least one
      single session of treatment with 532 nm neodymium-doped yttrium aluminum garnet
      (Nd:YAG) laser with contact cooling, fluencies ranging from 8 to 11.5 J/cm2 ,
      pulse duration ranging from 5 to 9 milliseconds and spot size ranging from 5 to
      10 mm. Objective analysis of percentage improvement based on 3D digital
      assessment of combined color and area improvement (global clearance effect [GCE])
      were performed. RESULTS: Median maximal improvement achieved during the treatment
      (GCEmax ) was 70.4%. Mean number of laser procedures required to achieve this
      improvement was 7.1 (ranging from 2 to 14)). Improvement of minimum 25% (GCE 25)
      was achieved by all patients, of minimum 50% (GCE 50) by 77.3%, of minimum 75%
      (GCE 75) by 38.6%, and of minimum 90% (GCE 90) by 13.64. CONCLUSION: Large spot
      532 nm laser is highly effective in the treatment of facial CM. 3D color and area
      image analysis provides an objective method to compare different methods of
      facial CM treatment in future studies. Lasers Surg. Med. 49:743-749, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28432682
TI  - Prognostic factors and survival in acral lentiginous melanoma.
AB  - BACKGROUND: Acral lentiginous melanoma (ALM) is a rare melanoma subtype that
      disproportionately afflicts people of colour. ALMs have a worse prognosis than
      other melanoma subtypes; this has been attributed to aggressive biological
      behaviour, more advanced stage at presentation and possible disparities in access
      to health care. OBJECTIVES: To examine, using comprehensive patient data and long
      term follow-up information in a well-characterized cohort, how patient, tumour
      and clinical management variables impact overall and melanoma-specific survival.
      METHODS: We characterized a consecutive cohort of 123 ALMs diagnosed from 1987 to
      2013 and analysed predictors of overall and melanoma-specific survival for their
      association with survival. RESULTS: Univariate hazard ratios and 95% confidence
      intervals using Cox regression models showed that increased Breslow depth,
      presence of ulceration, receipt of radiation, chemo- and vaccine therapy were
      associated with worse melanoma-specific survival. Notably, nonwhite
      race/ethnicity was not associated with worse overall or melanoma-specific
      survival. Multivariate modelling adjusting for patient, tumour and management
      variables revealed Breslow depth > 2 mm and disease extent as significantly
      associated with poor melanoma-specific survival. CONCLUSIONS: Melanoma-specific
      mortality among patients with ALM is associated with increased tumour thickness
      and more advanced stage at presentation, but not with race/ethnicity. Advanced
      tumour features at presentation and access to care may account for less
      favourable survival outcomes reported among nonwhite patients.

PMID- 28432683
TI  - Prospective evaluation of the diagnostic value of sensitive KIT D816V mutation
      analysis of blood in adults with suspected systemic mastocytosis.
AB  - BACKGROUND: Sensitive KIT D816V mutation analysis of blood has been proposed to
      guide bone marrow (BM) investigation in suspected systemic mastocytosis (SM). The
      aim of this prospective study was for the first time to compare the D816V status
      of the "screening blood sample" used to guide BM biopsy in suspected SM to the
      outcome of the subsequent BM investigation. METHODS: Fifty-eight adult patients
      with suspected SM were included. The outcome of sensitive KIT D816V analysis of
      blood was compared to the result of the BM investigation. RESULTS: Screening
      blood samples from 44 of 58 patients tested D816V-positive. In 43 of these, SM
      was subsequently diagnosed in the BM investigation. One patient with a D816V
      positive screening sample was diagnosed with monoclonal MC activation syndrome.
      Screening blood samples from 14 patients tested D816V-negative. SM was
      subsequently diagnosed in five of these, whereas nine patients did not fulfill
      any diagnostic SM criteria (excluding tryptase criterion). Of the 48 SM patients,
      90% tested D816V-positive. Thirteen SM patients presented with Hymenoptera venom
      induced anaphylaxis, no skin lesions, and baseline serum tryptase <=20 ng/mL. Of
      these, 92% tested D816V-positive in the screening blood sample. CONCLUSION: This
      prospective study demonstrates that a D816V-positive result in a screening blood
      sample identifies SM among patients with hymenoptera venom-induced anaphylaxis in
      whom the diagnosis would most probably have been missed, with potential severe
      implications. The observed false-negative screening results also underline that
      BM investigation is mandatory in all adult patients with clear signs of, or
      highly suspected SM, regardless of the KIT mutation status.

PMID- 28432684
TI  - Characterization of interactions of metal-containing nanoparticles with
      biomolecules by CE: An update (2012-2016).
AB  - The methodological developments and applications of CE related to studying
      biotransformations of metal-based nanoscale particles of impending medicinal use
      are overviewed. This is an update to a previous review article (Aleksenko, S. S.,
      Shmykov, A. Y., Oszwaldowski, S., Timerbaev, A. R., Metallomics 2012, 4, 1141
      1148) and it covers the research papers published within the last five years. As
      was anticipated in that review, CE can now be seen as a customary technique in
      the analysis of biomolecular interactions that exert an impact on the mechanism
      of action of nanoparticles, comprising metabolism, delivery, cell processing, and
      targeting. Different ways by which the CE method is applied for such monitoring,
      including conjugation mode, sample preparation, separation, and detection, are
      critically assessed. Special emphasis is put on examinations using inductively
      coupled plasma MS detection recent advent of which to the area made CE a
      versatile speciation tool for biomedical studies of nanomaterials containing
      metals.

PMID- 28432685
TI  - Chiral analysis of alpha-diimine Ru(II) and Fe(II) complexes by capillary
      electrophoresis using sulfated cyclodextrins as stereoselectors.
AB  - CE using randomly highly sulfated alpha-, beta-, and gamma-CDs (S-alpha-CD, S
      beta-CD, S-gamma-CD), sulfobutylether-beta-CD (SBE-beta-CD), single isomer (6-O
      sulfo) alpha-, beta-, and gamma-CDs, and their derivatives as stereoselectors was
      applied to chiral analysis of polypyridyl complexes of [Ru(bpy)3 ]2+ , [Ru(phen)3
      ]2+ , and [Fe(phen)3 ]2+ (bpy = 2,2'-bipyridine; phen = 1,10 phenanthroline). The
      best separations of Delta- and Lambda-enantiomers of the these complexes with
      high resolution (up to R1,2  = 7.0) and short analysis times (10-20 min) were
      achieved in the BGE composed of 22 mM NaOH/35 mM H3 PO4 , pH 2.4, containing 1.5
      6.0 mM S-alpha-CD or S-beta-CD, or SBE-beta-CD as chiral selectors. The developed
      method was applied to the assessment of enantiomeric purity of several samples of
      [Ru(bpy)3 ]2+ catalyst. CE experiments were performed in a homemade analyzer
      equipped with bare or hydroxypropylcellulose-coated fused-silica capillaries
      (total/effective length 40/29 cm, id/od 50/375 MUm) and an UV absorption detector
      operating at 206 nm. In addition to chiral analysis, apparent binding constants
      of the complexes of [Ru(bpy)3 ]2+ , [Ru(phen)3 ]2+ , and [Fe(phen)3 ]2+
      enantiomers with five sulfated CDs (S-alpha-CD, S-beta-CD, S-gamma-CD, SBE-beta
      CD, and 16Me-8S-gamma-CD) were determined from the dependence of their effective
      electrophoretic mobilities on the concentration of the CDs in the BGE by
      nonlinear regression analysis. Calculated apparent binding constants of these
      complexes were found to be in the (1.10-4.66) * 103  L/mol range. Moreover, it
      was shown that at selected concentrations of some S-CDs and suppressed or very
      low electroosmotic flow, the exceptional enantioseparations with infinite
      resolution could be achieved.

PMID- 28432686
TI  - High level of reduced glutathione contributes to detoxification of lipid peroxide
      derived reactive carbonyl species in transgenic Arabidopsis overexpressing
      glutathione reductase under aluminum stress.
AB  - Lipid peroxide-derived reactive carbonyl species (RCS), generated downstream of
      reactive oxygen species (ROS), are critical damage-inducing species in plant
      aluminum (Al) toxicity. In mammals, RCS are scavenged primarily by glutathione
      (reduced form of glutathione, GSH), but in plant Al stress, contribution of GSH
      to RCS detoxification has not been evaluated. In this study, Arabidopsis plants
      overexpressing the gene AtGR1 (accession code At3g24170), encoding glutathione
      reductase (GR), were generated, and their performance under Al stress was
      examined. These transgenic plants (GR-OE plants) showed higher GSH levels and
      GSH/GSSG (oxidized form of GSH) ratio, and an improved Al tolerance as they
      suffered less inhibition of root growth than wild-type under Al stress. Exogenous
      application of 4-hydroxy-2-nonenal, an RCS responsible for Al toxicity in roots,
      markedly inhibited root growth in wild-type plants. GR-OE plants suffered
      significantly smaller inhibition, indicating that the enhanced GSH level
      increased the capacity of RCS detoxification. The generation of H2 O2 due to Al
      stress in GR-OE plants was lower by 26% than in wild-type. Levels of various RCS,
      such as malondialdehyde, butyraldehyde, phenylacetaldehyde, (E)-2-heptenal and n
      octanal, were suppressed by more than 50%. These results indicate that high
      levels of GSH and GSH/GSSG ratio by GR overexpression contributed to the
      suppression of not only ROS, but also RCS. Thus, the maintenance of GSH level by
      overexpressing GR reinforces dual detoxification functions in plants and is an
      efficient approach to enhance Al tolerance.

PMID- 28432687
TI  - Impact of caring for patients with severe and complex disabilities on health care
      workers' quality of life: determinants and specificities.
AB  - AIM: Individuals with severe and complex disabilities, defined by a combination
      of profound intellectual impairment and serious motor deficit resulting in
      extreme dependence, often remain in hospital or at residential facilities. The
      aim of this study was to identify the determinants of quality of life (QoL) of
      238 health care workers (HCWs) caring for individuals with severe and complex
      disabilities. METHOD: We conducted a cross-sectional study. The recruitment of
      the HCWs was performed in five French centres specializing in patients with
      severe and complex disabilities. The selection criteria were age above 18 years,
      being an institutional referent HCW (a resource person coordinating various
      issues for or about the patient), and agreeing to participate. Sociodemographic,
      health, professional variables, and psycho-behavioural (QoL, burn-out, and coping
      strategies) data were collected. RESULTS: Of the 362 eligible HCWs, 65.7%
      returned the questionnaires. The scores of the physical and social dimensions of
      QoL were significantly lower, and the score of the psychological dimension
      significantly higher, than those of a comparison group. The main factors
      modulating QoL were age, financial difficulties, nature of coping strategy, and
      burn-out. INTERPRETATION: This research provides preliminary evidence that caring
      for patients with severe and complex disabilities affects the QoL of HCWs. These
      results support the need for optimization of the work environments for HCWs.

PMID- 28432688
TI  - Adult T-cell leukemia/lymphoma with subungual hematomas in all fingers and toes
      as the first manifestation.

PMID- 28432689
TI  - Viscosity based droplet size controlling in negative pressure driven droplets
      generator for large-scale particle synthesis.
AB  - The poor control and regulation of droplets limit the applications of negative
      pressure driven droplet generator (NPDDG). Here, we present a simple method to
      control droplet size in NPDDG via varying the oil viscosity. Depending on the
      infinite intersolubility of high viscous mineral oil and low viscous hexadecane,
      we obtain a series of oils with kinematic viscosities linearly varied from 4.2 to
      194.6 mm2 /s. By using these oils as continuous phases, monodisperse droplets are
      fabricated with controllable size in NPDDG. This viscosity-based droplet
      regulation method is effective, reliable, and compatible with scale-up processes.
      Compared with droplet generator driven by positive pressure, the presented method
      can fabricate hydrogel particles massively, without complicated multilayer chip
      structure and complex fluid controlling, which may extend the potential of NPDDG
      in droplets based high-throughput assay or large-scale materials synthesis.

PMID- 28432690
TI  - Sucking behaviour in infants born preterm and developmental outcomes at primary
      school age.
AB  - AIM: To determine the association between sucking in infants born preterm and
      developmental outcomes at 5 years. METHOD: Thirty-four infants were included
      (mean gestational age 30wks 4d, mean birthweight 1407g). The Neonatal Oral-Motor
      Assessment Scale was used longitudinally from 37 to 50 weeks postmenstrual age.
      At 5 years, we assessed motor skills, intelligence, language, verbal memory, and
      behavioural problems. Linear regression analyses were performed to test whether
      aspects of sucking behaviour predicted these developmental outcomes. Where linear
      regression was not appropriate, Spearman's correlation coefficients were
      calculated between sucking and developmental outcomes. RESULTS: Sucking was
      associated with total motor skills (B [unstandardized correlation coefficient for
      normally distributed data]=22.66, 95% confidence interval [CI] 6.61 to 38.71),
      balance (Spearman's rho=0.64, p<0.001), total intelligence (B=-1.16, 95% CI -1.89
      to -0.44, B=10.48, 95% CI 0.39 to 20.71, B=-2.22, 95% CI -3.42 to -1.02), verbal
      intelligence (B=-0.95; 95% CI -1.83 to -0.07, B=-2.02; 95% CI -3.55 to -0.49),
      performance intelligence (B=-1.34, 95% CI -2.13 to -0.54, B=12.36, 95% CI 1.13 to
      23.60, B=-2.37, 95% CI -3.75 to -0.96), and language (B=-1.78, 95% CI -3.36 to 
      0.19). All associations were in the same direction: the better the sucking, the
      higher the test scores. Verbal memory and behavioural problems were not
      associated with sucking. INTERPRETATION: Abnormal sucking between 42 weeks and 50
      weeks postmenstrual age may reflect abnormal neurological functioning in children
      born preterm.

PMID- 28432691
TI  - Tenapanor administration and the activity of the H+ -coupled transporter PepT1 in
      healthy volunteers.
AB  - AIM: Tenapanor (RDX5791/AZD1722), an inhibitor of gastrointestinal Na+ /H+
      exchanger NHE3, is being evaluated for the treatment of patients with
      constipation-predominant irritable bowel syndrome and the treatment of
      hyperphosphataemia in patients with chronic kidney disease on dialysis. By
      reducing intestinal H+ secretion, inhibition of NHE3 by tenapanor could
      indirectly affect H+ -coupled transporter activity, leading to drug-drug
      interactions. We investigated the effect of tenapanor on the activity of the H+ 
      coupled peptide transporter PepT1 via assessment of the pharmacokinetics of
      cefadroxil - a compound transported by PepT1 - in healthy volunteers. METHODS: In
      this open-label, two-period crossover, phase 1 study (NCT02140281), 28 volunteers
      received in random order: a single dose of cefadroxil 500 mg for 1 day; and
      tenapanor 15 mg twice daily over 4 days followed by single doses of both
      cefadroxil 500 mg and tenapanor 15 mg on day 5. There was a 4-day washout between
      treatment periods. RESULTS: Cefadroxil exposure was similar when administered
      alone or in combination with tenapanor {geometric least-squares mean ratios
      [(cefadroxil + tenapanor)/cefadroxil] (90% confidence interval): area under the
      concentration-time curve 93.3 (90.6-96.0)%; maximum concentration in plasma 95.9
      (89.8-103)%}. Tenapanor treatment caused a softening of stool consistency and an
      increase in stool frequency, consistent with its expected pharmacodynamic effect.
      No safety concerns were identified and tenapanor was not detected in plasma.
      CONCLUSIONS: These results suggest that tenapanor 15 mg twice daily does not have
      a clinically relevant impact on the activity of the H+ -coupled transporter PepT1
      in humans. This may guide future research on drug-drug interactions involving
      NHE3 inhibitors.

PMID- 28432692
TI  - Functional status and amount of hip displacement independently affect acetabular
      dysplasia in cerebral palsy.
AB  - AIM: Acetabular dysplasia is the one of main causes of hip displacement in
      patients with cerebral palsy (CP). Although several studies have shown a
      relationship between hip displacement and acetabular dysplasia, relatively few
      have evaluated the association between quantitative acetabular dysplasia and
      related factors, such as Gross Motor Function Classification System (GMFCS)
      level. METHOD: We performed a morphometric analysis of the acetabulum in patients
      with CP using multiplanar reformation of computed tomography data. The three
      directional acetabular indices (anterosuperior, superolateral, and
      posterosuperior) were used to evaluate acetabular dysplasia. Consequently, linear
      mixed-effects models were used to adjust for related factors such as age, sex,
      GMFCS level, and migration percentage. RESULTS: A total of 176 patients (mean age
      9y 5mo, range 2y 4mo-19y 6mo; 104 males, 72 females) with CP and 55 typically
      developing individuals (mean age 13y 6mo, range 2y 5mo-19y 10mo; 37 males, 18
      females) in a comparison group were enrolled in this study. Statistical modelling
      showed that all three directional acetabular indices independently increased with
      GMFCS level (p<0.001) and migration percentage (p<0.001). INTERPRETATION:
      Acetabular dysplasia was independently affected by both the amount of hip
      displacement and the GMFCS level. Thus, physicians should consider not only the
      migration percentage but also three-dimensional evaluation in patients at high
      GMFCS levels.

PMID- 28432693
TI  - Multimodal neurophysiological monitoring in healthy infants born at term:
      normative continuous somatosensory evoked potentials data.
AB  - AIM: To describe accurate, standardized 1h-multimodal neurophysiological
      monitoring (1h-MNM), while simultaneously recording VEEG, aEEG, and SEP-C
      bilaterally from median nerves, and to collect neonatal normative SEP-C data
      related to behavioural states. METHOD: Twenty healthy, term newborn infants (13
      males, 7 females; gestational age 37-42wks; mean 39.6wks, standard deviation [SD]
      1.3wks) underwent 1h-MNM within 2 days of life, with focus on recording of the
      SEP-C (band-pass setting 1-100 Hz, rate of stimulation 1.1 Hz, 50 alternate
      stimuli). RESULTS: 1h-MNM was easily obtained with identification of cervical
      (N13) and cortical (N1, P1) SEP-C responses in all infants. SEP-C minimal and
      maximum N1 latencies/N1-P1 amplitudes were identified, bilaterally, during
      periods of spontaneous sleep active-quiet-active (AS-QS-AS) and quiet
      wakefulness. Minimal latencies and amplitudes occurred in 60% of active
      sleep/quiet-wakefulness, with the maximums in 70% of quiet sleep. The SEP-C mean
      values were latencies of N13=13.6ms (SD 1.4ms) and N1=33.6ms (SD 3.9ms) to 34.2ms
      (SD 4.8ms) in left and right hemisphere respectively; central-conduction-time
      (CCT) (N13-N1), 20.0ms (SD 4.3ms) to 20.6ms (SD 4.8ms); N1-P1 amplitude=4.6ms (SD
      2.7ms) to 3.8MUV (SD 2.2MUV). INTERPRETATION: 1h-MNM can record simultaneously
      VEEG/aEEG/SEP-C in newborn infants, showing the modulation of SEP cortical
      responses in relation to behavioural states in all infants studied using an
      appropriate neonatal method. We emphasize the importance of obtaining neonatal
      SEP-C normative data to better identify pathological findings in neonatal brain
      injury.

PMID- 28432694
TI  - Allergic contact dermatitis caused by diethyl thiourea in a neoprene-containing
      wet suit.

PMID- 28432695
TI  - Recent strategies toward microfluidic-based surface-enhanced Raman spectroscopy.
AB  - Surface-enhanced Raman spectroscopy (SERS) is an extremely powerful analytical
      tool, which not only yields information about the molecular structure of the
      analyte in the form of characteristic vibrational spectrum but also gives
      sensitivities approaching those in fluorescence spectroscopy. The SERS
      measurement on the microfluidic platform provides possibility to manufacture the
      device with design perfectly fulfilling the needs of the application with minimal
      sample consumption. This review aims at describing basic strategies for SERS
      measurement in microfluidic devices published in the last decade and covers
      current trends in microfluidics with SERS detection in the field of bioanalysis
      and approaches toward on-line coupling of liquid-based separation techniques with
      SERS detection.

PMID- 28432697
TI  - Refractory acrodermatitis continua of Hallopeau successfully treated with oral
      alitretinoin.

PMID- 28432696
TI  - Systematic review of self-management interventions for people with eczema.
AB  - Eczema is a common long-term condition, but inadequate support and information
      can lead to poor adherence and treatment failure. We have reviewed the
      international literature of interventions designed to promote self-management in
      adults and children with eczema. MEDLINE, MEDLINE in process, Embase, CINAHL and
      the Global Resource for EczemA Trials database were searched from their inception
      to August 2016, for randomized controlled trials. Two authors independently
      applied eligibility criteria, assessed risk of bias for all included studies and
      extracted data. Twenty studies (3028 participants) conducted in 11 different
      countries were included. The majority (n = 18) were based in secondary care and
      most (n = 16) targeted children with eczema. Reporting of studies, including
      descriptions of the interventions and the outcomes themselves, was generally
      poor. Thirteen studies were face-to-face educational interventions, five were
      delivered online and two were studies of written action plans. Follow-up in most
      studies (n = 12) was short term (up to 12 weeks). Only six trials specified a
      single primary outcome. There was limited evidence of effectiveness. Only three
      studies collected and reported outcomes related to cost and just one study
      undertook any formal cost-effectiveness analysis. In summary, we have identified
      a general absence of well-conducted and well-reported randomized controlled
      trials with a strong theoretical basis. Therefore, there is still uncertainty
      about how best to support self-management of eczema in a clinically effective and
      cost-effective way. Recommendations on design and conduct of future trials are
      presented.

PMID- 28432698
TI  - Quantitative evaluation of metal artifacts using different CBCT devices, high
      density materials and field of views.
AB  - OBJECTIVE: To objectively compare the influence of different cone-beam computed
      tomography (CBCT) devices, high-density materials and field of views (FOVs) on
      metal artifact expression. MATERIAL AND METHODS: For this in vitro study, three
      customized acrylic resin phantoms containing high-density materials cylinders:
      titanium, copper-aluminum alloy and amalgam were scanned on three CBCT devices
      using high-resolution protocols, same voxel size (0.2 mm) and different FOVs.
      After fully automatic segmentation and image registration, the same region of
      interest was defined for the small and medium FOVs. The difference between the
      segmented and the real volume of the metal cylinders was assessed. Moreover for
      each segmented slice, the area difference between the segmented and the real
      axial section was determined. The artifacts on the background were measured as
      normalizing standard deviation of voxel values in the vicinity of the cylinder,
      in three different distances. RESULTS: Considerable differences were observed in
      volume measurements for all CBCTs devices and materials for both FOV sizes (up to
      67%). The slice per slice area analysis indicated higher artifacts at the edges
      of the metal cylinder. Within the materials, amalgam and titanium had,
      respectively, the worst and best artifact expression in all the CBCT devices.
      Standard deviation values varied differently between the three distances in each
      device. CONCLUSION: Our in vitro study showed that different CBCT devices, high
      density materials and FOV should be considered while evaluating CBCT images. More
      carefully, diagnosis conclusions should be drawn in images containing amalgam and
      copper-aluminum alloy.

PMID- 28432699
TI  - Sensitive methods and improved screening strategies are needed for the detection
      of pig viruses.

PMID- 28432700
TI  - Serum H-ficolin levels: Clinical association with interstitial lung disease in
      patients with systemic sclerosis.
AB  - Ficolins, a group of oligomeric lectins consisting of three isoforms (H-, L- and
      M-ficolin), contribute to innate immunity via activating the complement pathway
      and/or acting directly as opsonins against pathogens and apoptotic cells. Because
      apoptotic cells likely drive the development of systemic sclerosis (SSc) partly
      through innate immunity, we assessed the clinical association of serum H-ficolin
      levels in SSc patients. Despite no difference in serum H-ficolin levels between
      SSc and control subjects, SSc patients with decreased serum H-ficolin levels
      tended to have a higher prevalence of interstitial lung disease (ILD). More
      importantly, serum H-ficolin levels inversely correlated with ground-glass
      opacity score on chest computed tomography in SSc-ILD patients. Therefore, H
      ficolin-related innate immunity may be involved in SSc-ILD development.

PMID- 28432701
TI  - Ovarian follicle development and genital tract characteristics in different
      birthweight gilts at 150 days of age.
AB  - In the last decades, selection for improved prolificacy has resulted in higher
      litter sizes and has thereby increased the proportion of low birthweight (LW)
      piglets. It is well documented that LW piglets have lower growth performance,
      muscle accretion and poor carcass quality. However, little is known about the
      relations of birthweight with subsequent reproductive performance in gilts. This
      study investigated the effects of birthweight on reproductive tract and ovarian
      follicle development in 150-day-old gilts. Twenty eight female pigs of different
      birthweight ranges (high-HW: 1.8-2.2 kg; low-LW: 0.8-1.2 kg) from higher parity
      commercial sows were reared until 150 days of age, and their body weights were
      recorded at weaning, end of nursery and end of the grower-finisher phase. The
      animals were killed and their reproductive tracts collected for biometrical and
      histomorphometrical analysis. LW gilts showed significantly lower body weights
      and growth rates during all phases of production compared to their HW
      counterparts (p < .01). Most biometrical measurements of the reproductive tract
      were similar between the experimental groups, except vaginal length and the
      gonadossomatic index (relative ovarian weight), which were affected by
      birthweight class (p < .05). LW females also showed fewer medium size (3-5 mm; p
      < .01) ovarian follicles, pre-antral follicles (p < .07) and more atretic
      follicles per ovarian cortex area (p < .05). Therefore, besides the effects on
      post-natal growth performance, birthweight affects vaginal length and the
      follicular dynamics process, which may impair the reproductive performance of
      replacement gilts.

PMID- 28432702
TI  - Tunable Porous Coordination Polymers for the Capture, Recovery and Storage of
      Inhalation Anesthetics.
AB  - The uptake of inhalation anesthetics by three topologically identical frameworks
      is described. The 3D network materials, which possess square channels of
      different dimensions, are formed from the relatively simple combination of ZnII
      centres and dianionic ligands that contain a phenolate and a carboxylate group at
      opposite ends. All three framework materials are able to adsorb N2 O, Xe and
      isoflurane. Whereas the framework with the widest channels is able to adsorb
      large quantities of the various guests from the gas phase, the frameworks with
      the narrower channels have superior binding enthalpies and exhibit higher levels
      of retention. The use of ligands in which substituents are bound to the aromatic
      rings of the bridging ligands offers great scope for tuning the adsorption
      properties of the framework materials.

PMID- 28432703
TI  - Selective Calixarene-Directed Synthesis of MXene Plates, Crumpled Sheets,
      Spheres, and Scrolls.
AB  - Fully exploiting the electronic and mechanical properties of 2D laminar materials
      not only requires efficient and effective means of their exfoliation into low
      dimensional layers, but also necessitates a means of changing their morphology so
      as to explore any enhancement that this may offer. MXenes are a rapidly emerging
      new class of such laminar materials with unique properties. However, access to
      other morphologies of MXenes has not yet been fully realised. To this end we have
      developed the synthesis of MXenes (Ti2 C) as plates, crumpled sheets, spheres and
      scrolls, which involves selective intercalation of p-phosphonic calix[n]arenes,
      with control in morphology arising from the choice of the size of the macrocycle,
      n=4, 5, 6, or 8. This opens up wider avenues of discovery/design for new
      morphologies from the wider family of MXenes beyond Ti2 C, along with
      opportunities to exploit any new physico-chemical properties proffered.

PMID- 28432704
TI  - Human galectin-9 on the porcine cells affects the cytotoxic activity of M1
      differentiated THP-1 cells through inducing a shift in M2-differentiated THP-1
      cells.
AB  - BACKGROUND: In xenotransplantation, immune rejection by macrophages occurs
      rapidly and remains a major obstacle. Studies to control immune rejection in
      macrophages have been continuing to date. Recent studies have reported that human
      galectin-9 (hGal-9) can regulate the function of regulatory T cells (Treg), as
      well as cytotoxicity T cells (CTL) and natural killer cells (NK). Although the
      effect of hGal-9 on lymphocytes has been well studied, the relationship between
      hGal-9 and myeloid cells has been scarcely studied. METHODS: To confirm the
      decreased cytotoxic activity effect by hGal-9 in M1-differentiated THP-1 cells,
      we established the hGal-9 expressing transgenic porcine cell line. hGal-9 siRNA
      was transfected to transgenic cells and recombinant hGal-9 (rhGal-9) was treated
      to co-culturing condition, and then, flow cytometry assay was conducted for
      analyzing the cytotoxic activity of M1-differentiated THP-1 cells. Related
      inflammatory cytokines (IL-1beta, IL-10, TNF-alpha, IL-6, IL-12, IL-23, and TGF
      beta) and related enzymes (iNOS and Arginase 1) were analyzed by qPCR and Western
      blot assay. To identify the shift in M1/M2-differentiated THP-1 cells, expression
      levels of CCR7, CD163, iNOS, and Arginase 1 and population of M2 marker positive
      cells were analyzed. RESULTS: The expression levels of pro-inflammatory cytokines
      in M1-differentiated THP-1 cells co-cultured with hGal-9-expressing porcine
      kidney epithelial cells were decreased, but not in co-cultured THP-1 cells.
      However, the expression levels of anti-inflammatory cytokines were also increased
      in co-cultured M1-differentiated THP-1 cells. The cytotoxicity effect of M1
      differentiated THP-1 cells on transgenic cells was decreased while the expression
      levels of anti-inflammatory cytokines and M2 macrophages-related molecules were
      increased. M2 differentiation program was turned on while M1 program was turned
      down by enhancing the phosphorylation levels of Akt and PI3K and the expression
      level of PPAR-gamma. Due to these changes, differentiation of M2 program was
      enhanced in cells co-cultured with hGal-9. CONCLUSIONS: These data suggested that
      hGal-9 has a reduction in M1-differentiated THP-1 cell cytotoxic activity-related
      acute immune rejection in pig-to-human xenotransplantation in addition to its
      role in lymphoid lineage immune cell regulation.

PMID- 28432705
TI  - Prognosis of infantile food protein-induced enterocolitis syndrome in Japan.
AB  - BACKGROUND: Although serum C-reactive protein (CRP) and the percentage of
      eosinophils in peripheral blood (Eo) are increased at onset in infants with food
      protein-induced enterocolitis syndrome (FPIES), the relationship of these
      laboratory findings to prognosis is presently unknown. METHODS: Correlation of
      serum CRP and Eo at onset with prognosis was analyzed in 32 patients with FPIES
      caused by cow's milk (CM). RESULTS: The rate of tolerance acquisition was 18.8%,
      56.3%, 87.5%, and 96.9% at the ages of 6, 12, 24, and 36 months, respectively.
      Serum CRP increased in 50% of subjects at onset (median, 0.21 mg/dL; range, <0.20
      18.2 mg/dL) and Eo was elevated in 71.9% of subjects at onset (median, 7.1%;
      range, 1.0-50.5%). Age at tolerance acquisition was significantly positively
      correlated with serum CRP at onset (r = 0.45, P < 0.01), and significantly
      negatively correlated with Eo at onset (r = -0.36, P < 0.05). Although CM
      specific immunoglobulin E antibody (sIgE) was positive in nine of 32 FPIES
      patients at onset (median, 0.93; range, 0.38-18.9 kU/L), it decreased thereafter.
      CM-sIgE at onset did not correlate significantly with prognosis (r = 0.22, P >
      0.05). CONCLUSIONS: Serum CRP is not only an indicator of the activity of
      intestinal inflammation, it is also a useful parameter of poor prognosis in
      FPIES. In contrast, eosinophilia at onset could be used as a marker of good
      prognosis, suggesting that it has some beneficial effects in the pathophysiology
      of FPIES.

PMID- 28432706
TI  - Varied pathological and therapeutic response effects associated with CHCHD2
      mutant and risk variants.
AB  - Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix
      domain containing 2 (CHCHD2) have been associated with late-onset Parkinson
      disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking.
      Utilizing transgenic Drosophila model, we examined the relative pathophysiologic
      effect of the pathogenic (c.182C>T, p.Thr61Ile and c.434G>A, p.Arg145Gln) and the
      risk (c.5C>T, p.Pro2Leu) CHCHD2 variants. All the transgenic models exhibited
      locomotor dysfunction that could be exacerbated by rotenone exposure,
      dopaminergic neuron degeneration, reduction in lifespan, mitochondrial
      dysfunction, oxidative stress, and impairment in synaptic transmission. However,
      both mutants showed more severe early motor dysfunction, dopaminergic neuronal
      loss, and higher hydrogen peroxide production compared with the risk variant.
      p.Thr61Ile (co-segregated in three independent PD families) displayed the most
      severe phenotype followed by p.Arg145Gln (present only in index patient). We
      treated the transgenic flies with Ebselen, a mitochondrial hydrogen peroxide
      scavenger compound; Ebselen appears to be more effective in ameliorating motor
      function in the mutant than the risk variant models. We provide the first in vivo
      evidence of the pathological effects associated with CHCHD2 mutations. There was
      a difference in the pathological and drug response effects between the pathogenic
      and the risk variants. Ebselen may be a useful neuroprotective drug for carriers
      of CHCHD2 mutations.

PMID- 28432707
TI  - Suberoylanilide hydroxamic acid, a novel histone deacetylase inhibitor, improves
      the development and acetylation level of miniature porcine handmade cloning
      embryos.
AB  - Histone deacetylase inhibitors (HDACis) can change the histone acetylation and
      significantly enhance the developmental competence of the pre-implantation SCNT
      embryo. To select a proper histone deacetylase inhibitor to improve the success
      rate and potentially developmental ability of handmade cloning (HMC) embryos of
      miniature porcine, we compared the effect of two histone deacetylase inhibitors
      (SAHA vs. VPA) on HMC embryo development, their histone acetylation level and the
      expression level of relevant genes. The blastocyst rate and number of blastocyst
      cells of HMC embryos treated with SAHA (SAHA-HMC) or VPA (VPA-HMC) were
      significantly higher than those of control (Control-HMC), respectively, but there
      were no significant difference between SAHA-HMC and VPA-HMC groups. In addition,
      the acetylation level (AcH4K8) of Control-HMC and VPA-HMC embryos at the
      blastocyst stage, respectively, was significantly lower than that of in vitro
      fertilized (IVF) and SAHA-HMC embryos. However, the acetylation H4K8 of the
      blastocysts had no significant difference between SAHA-HMC and the IVF groups.
      The SAHA-HMC blastocysts indicated comparative expression levels of Oct4 and
      HDAC1 (histone deacetyltransferase gene) with those of IVF blastocysts. In
      contrast, the expression levels of Oct4 were lower and those of HDAC1 were higher
      in the VPA-HMC and Control-HMC blastocysts, respectively, compared to those of
      the IVF blastocysts. Our results demonstrated that the HMC embryos treated by
      SAHA could promote the pre-implantation development and increase the levels of
      histone H4K8 acetylation and the expression of the OCT4 gene, yet decrease the
      expression of the HDAC1 gene to the comparable level of the IVF embryos. Our
      results proved that SAHA may be a better histone deacetylase inhibitor for
      porcine HMC compared to VPA, and furthermore, it may indicate that SAHA can
      effectively correct the abnormal histone acetylation during the HMC embryo
      development and subsequently improve the full-term developmental potential of the
      HMC embryos after embryo transplantation.

PMID- 28432708
TI  - In vitro production of porcine zygotes using intracytoplasmic injection of
      vitrified sperm.
AB  - The objectives of this study were to evaluate if vitrified porcine spermatozoa
      are able to maintain their capacity to produce zygotes in vitro using
      intracytoplasmic sperm injection (ICSI) and to evaluate the zygote development in
      two in vitro atmospheric conditions: 5% CO2 and tri-gas. A group of porcine
      oocytes maturated in vitro were injected with vitrified-warmed sperm (treatment
      group) and another group, with sperm diluted and conserved at 17 degrees C
      (control group). To evidence parthenogenetic activation, some oocytes were
      submitted to a Sham test. The injected oocytes were cultured in G1 medium at 38
      degrees C, 100% humidity and 5% CO2 or tri-gas. No significant differences (p >
      .05) were observed in embryo development between the oocytes injected with
      vitrified-warmed sperm (31.8%; 36/113), and those injected with semen diluted and
      conserved at 17 degrees C (35.5%; 32/90), when cultured in 5% CO2 or under tri
      gas atmosphere (42.9%; 39/91 vs. 34.2%; 26/76, respectively). No significant
      differences (p > .05) were observed in the percentage of pronuclei (PN) obtained
      between 5% CO2 and tri-gas, within each treatment either. Of the 52 oocytes
      submitted to the Sham test, only two presented a female PN (activation)
      indicating that the PN observed in the treatment group were a product of
      fertilization and not parthenogenetic activation. To conclude, porcine sperm
      vitrified using spheres, at a concentration of 5 * 106  spermatozoa/ml in TALP
      medium with 1% bovine serum albumin (BSA), conserve condensed and intact
      chromatin capable of producing early embryo development up to the pronuclear
      stage.

PMID- 28432709
TI  - A new modality for the estimation of corrected flow time via electrocardiography
      as an alternative to Doppler ultrasonography.
AB  - BACKGROUND: Evaluation of corrected flow time (FTc) via ultrasonography is one of
      the suggested modalities for the assessment of intravascular volume status. This
      study aimed to compare the results of FTc of carotid artery measured via
      ultrasonography, as a measure of mechanical outcome of the cardiac cycle, with
      the results of FTc estimation from a new modified formula via electrocardiography
      (ECG), as a measure of electrical function of the cardiac cycle. METHODS: Healthy
      volunteers were evaluated before and after a passive leg raising (PLR) maneuver.
      FTc was measured concurrently before and after PLR via a modified method from ECG
      and via ultrasonography of the carotid artery. RESULTS: A total number of 98
      healthy volunteers (51 women and 47 men) with a mean age of 30.69 +/- 6.28 years
      were included. There was a significant correlation between FTc measured by
      ultrasonography and estimated by ECG both before PLR and after PLR (r = .878, p <
      .0001 and r = .797, p < .0001, respectively). Changes in FTc were slightly higher
      in measurements by ultrasonography compared to estimations by ECG (22.33 +/-
      17.15 ms0.5 vs. 15.86 +/- 14.25 ms0.5 , p = .001). CONCLUSION: Estimation of FTc
      via ECG is potentially an effective and feasible method for the assessment of
      volume status at the clinical settings. Further investigations should determine
      the significance of differences that may be observed between ultrasonography and
      ECG in patients with either dehydration or volume overload and in the need of
      real-time volume status assessment.

PMID- 28432710
TI  - Medical students' perceptions of the importance of exercise and their perceived
      competence in prescribing exercise to older people.
AB  - OBJECTIVE: To determine the effects of a 4.5-week geriatric medicine course on
      fifth year medical students' perception of the importance of and their competence
      in prescribing exercise to older people. METHODS: The modified Exercise and
      Physical Activity Competence Questionnaire was administered to 81 students before
      and after the course. Scores ranged from 0 to 6. One open-ended question about
      perceived barriers to exercise prescription was asked. RESULTS: Students'
      perceptions of the importance of designing an exercise prescription (P = 0.038),
      determining the training heart rate (P = 0.021), determining the body mass index
      (P > 0.001), referring an older person to an exercise program (P > 0.001) and
      identifying age-related limitations (P = 0.029) improved significantly after the
      course. Students' self-perceived competence improved significantly across all
      items (P > 0.001). Barriers to exercise prescription included lack of: knowledge
      (57%), patient compliance (39%) and time (33%). CONCLUSION: A geriatric medicine
      course contributes to improved senior medical students' perceptions of importance
      of and their competence in prescribing exercise to older people.

PMID- 28432711
TI  - VDR gene methylation as a molecular adaption to light exposure: Historic, recent
      and genetic influences.
AB  - OBJECTIVES: The vitamin D receptor (VDR) is a member of the nuclear receptor
      family of transcription factors. We examined whether degree of VDR gene
      methylation acts as a molecular adaptation to light exposure. We explored this in
      the context of photoperiod at conception, recent UV irradiance at 305 nm, and
      gene-latitude effects. METHODS: Eighty subjects were examined for VDR gene-CpG
      island methylation density. VDR gene variants were also examined by PCR-RFLP.
      RESULTS: Photoperiod at conception was significantly positively related to VDR
      methylation density, explaining 17% of the variance in methylation (r2  = 0.17; P
      = .001). Within this model, photoperiod at conception and plasma 25(OH)D
      independently predicted methylation density at the VDR-CpG island. Recent UV
      exposure at 305 nm led to a fivefold increase in mean methylation density (P =
      .02). Again, UV exposure and plasma 25(OH)D independently predicted methylation
      density at the VDR-CpG island. In the presence of the BsmI mutant allele,
      methylation density was increased (P = .01), and in the presence of the TaqI or
      FokI mutant allele, methylation density was decreased (P = .007 and .04
      respectively). Multivariate modelling suggests plasma 25(OH)D, photoperiod at
      conception, recent solar irradiance, and VDR genotype combine as independent
      predictors of methylation at the VDR-CpG island, explaining 34% of the variance
      in methylation (R2  = 0.34, P < .0001). CONCLUSIONS: Duration of early-life light
      exposure and strength of recent irradiance, along with latitudinal genetic
      factors, influence degree of VDR gene methylation consistent with this epigenetic
      phenomenon being a molecular adaptation to variation in ambient light exposure.
      Findings contribute to our understanding of human biology.

PMID- 28432712
TI  - Stroke etiology and collaterals: atheroembolic strokes have greater collateral
      recruitment than cardioembolic strokes.
AB  - BACKGROUND AND PURPOSE: Chronic hypoperfusion from athero-stenotic lesions is
      thought to lead to better collateral recruitment compared to cardioembolic
      strokes. It was sought to compare collateral flow in stroke patients with atrial
      fibrillation (AF) versus stroke patients with cervical atherosclerotic steno
      occlusive disease (CASOD). METHOD: This was a retrospective review of a
      prospectively collected endovascular database. Patients with (i) anterior
      circulation large vessel occlusion stroke, (ii) pre-treatment computed tomography
      angiography (CTA) and (iii) intracranial embolism from AF or CASOD were included.
      CTA collateral patterns were evaluated and categorized into two groups:
      absent/poor collaterals (CTA collateral score 0-1) versus moderate/good
      collaterals (CTA collateral score 2-4). CT perfusion was also utilized for
      baseline core volume and evaluation of infarct growth. RESULTS: A total of 122
      patients fitted the inclusion criteria, of whom 88 (72%) had AF and 34 (27%)
      CASOD. Patients with AF were older (P < 0.01) and less often males or smokers (P
      = 0.04 and P < 0.01 respectively). Baseline National Institutes of Health Stroke
      Scale and Alberta Stroke Program Early CT Score were comparable between groups.
      Collateral scores were lower in the AF group (P = 0.01) with patients having poor
      collaterals in 28% of cases versus 9% in the CASOD group (P = 0.03). Mortality
      rates (20% vs. 0%; P = 0.02) were higher in the AF patients whilst rates of any
      parenchymal hemorrhage (6% vs. 26%; P < 0.01) were higher in the CASOD group. On
      multivariable analysis, CASOD was an independent predictor of moderate/good
      collaterals (odds ratio 4.70; 95% confidence interval 1.17-18.79; P = 0.03).
      CONCLUSIONS: Atheroembolic strokes seem to be associated with better collateral
      flow compared to cardioembolic strokes. This may in part explain the worse
      outcomes of AF-related stroke.

PMID- 28432713
TI  - Case of recurrent severe cellulitis and cutaneous candidiasis during psoriasis
      treatment with ustekinumab.

PMID- 28432714
TI  - High human cytomegalovirus DNAemia early post-transplantation associates with
      irreversible and progressive loss of renal function - a retrospective study.
AB  - Transplant recipients are prone to viral infections, which could affect renal
      transplantation outcome. Our aim was to assess the effects of early human
      cytomegalovirus (CMV) DNAemia on transplant renal function. A total of 264 (age
      50.9 +/- 13.5; male 55%) renal transplantation recipients undergoing preemptive
      anti-CMV therapy were retrospectively categorized based on early (<3 months post
      Tx) CMV peak viral load (PVL); PVL <= 536, PVL536-6310, or PVL > 6310
      International Units/ml (IU/ml). Estimated glomerular filtration rate (eGFR) was
      analyzed between 1 and 36 months post-transplantation with Kruskal-Wallis test,
      linear regression, and a linear mixed-effects model. CMV infection was detectable
      in 113 (43%) recipients within 49 [38-67] days. Subjects with PVL > 6310 had
      statistically significant ~5-13 ml/min lower eGFR between 3 and 36 months
      compared to PVL <= 536 and PVL536-6310. eGFR declined from 46.1 to 40.7
      ml/min/1.73 m2 (-12%) over 3 years, and the annual decrease for pronounced
      infection with high PVL was 2.0 ml/min/1.73 m2 faster than for noninfected or
      mildly infected subjects. In conclusion, high CMV DNAemia early after renal
      transplantation was associated with significant loss of renal function, from
      which subjects did not recover. The severity of infection (high PVL early post
      transplantation), more than the infection per se, was related to irreversible and
      progressive loss of renal function.

PMID- 28432715
TI  - Complications of pregnancy and labour in women with Klippel-Trenaunay syndrome: a
      nationwide cross-sectional study.
AB  - OBJECTIVE: To evaluate complications of pregnancy, including thromboembolism, in
      women with extensive vascular malformations associated with Klippel-Trenaunay
      syndrome (KTS). DESIGN: Nationwide cross-sectional study. SETTING: Two tertiary
      expert centres and the Dutch Klippel-Trenaunay patient organisation. SAMPLE:
      Adult women with KTS. METHODS: Patients with KTS were invited to participate in a
      comprehensive online survey about their obstetric history. Reference data on
      pregnancy outcomes and complications of non-diseased women were collected from
      population-based cohorts from the literature. MAIN OUTCOME MEASURES: Prevalence
      of complications, specifically venous thromboembolism and postpartum haemorrhage.
      RESULTS: Sixty women completed the survey. Seventeen patients did not conceive,
      of whom three refrained from pregnancy because of KTS. A total of 97 pregnancies
      and 86 deliveries were reported in 43 patients. KTS-related symptoms were
      aggravated during pregnancy in 43% of patients. Deep vein thrombosis was present
      in 5.8% and pulmonary embolism was present in 2.3% of pregnancies, which was
      extremely high compared with the reference population (P < 0.0001), with a
      relative risk of 108.9 (95% confidence interval, 95% CI 46.48-255.03) and 106.2
      (95% CI 26.97-418.10), respectively. Severe postpartum haemorrhage (PPH) occurred
      in 11% of KTS pregnancies, compared with 5.8% of pregnancies in the reference
      population (relative risk, RR 1.81, 95% CI 0.97-3.37, P = 0.06). CONCLUSIONS: Our
      data suggest that women with KTS have a significant risk of venous thromboembolic
      events, severe postpartum haemorrhage, and aggravation of KTS symptoms during
      pregnancy, and in early postpartum period. Obstetricians should counsel patients
      about these risks in the preconception phase. Antithrombotic prophylaxis should
      be considered in the obstetric management of patients with KTS. TWEETABLE
      ABSTRACT: High risk of complications during pregnancy and labour in women with
      Klippel-Trenaunay syndrome.

PMID- 28432717
TI  - Depressive symptoms in older adults awaiting cataract surgery: methodological and
      statistical issues.

PMID- 28432718
TI  - Long-acting reversible contraception: conflicting perspectives of advocates and
      potential users.

PMID- 28432716
TI  - Deciphering Tacrolimus-Induced Toxicity in Pancreatic beta Cells.
AB  - beta Cell transcription factors such as forkhead box protein O1 (FoxO1), v-maf
      musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), pancreatic and
      duodenal homeobox 1, and neuronal differentiation 1, are dysfunctional in type 2
      diabetes mellitus (T2DM). Posttransplant diabetes mellitus resembles T2DM and
      reflects interaction between pretransplant insulin resistance and
      immunosuppressants, mainly calcineurin inhibitors (CNIs). We evaluated the effect
      of tacrolimus (TAC), cyclosporine A (CsA), and metabolic stressors (glucose plus
      palmitate) on insulinoma beta cells in vitro and in pancreata of obese and lean
      Zucker rats. Cells were cultured for 5 days with 100 MUM palmitate and 22 mM
      glucose; CsA (250 ng/mL) or TAC (15 ng/mL) were added in the last 48 h. Glucose
      plus palmitate increased nuclear FoxO1 and decreased nuclear MafA. TAC in
      addition to glucose plus palmitate magnified these changes in nuclear factors,
      whereas CsA did not. In addition to glucose plus palmitate, both drugs reduced
      insulin content, and TAC also affected insulin secretion. TAC withdrawal or
      conversion to CsA restored these changes. Similar results were observed in
      pancreata of obese animals on CNIs. TAC and CsA, in addition to glucose plus
      palmitate, induced comparable inhibition of calcineurin and nuclear factor of
      activated T cells (NFAT); therefore, TAC potentiates glucolipotoxicity in beta
      cells, possibly by sharing common pathways of beta cell dysfunction. TAC-induced
      beta cell dysfunction is potentially reversible. Inhibition of the calcineurin
      NFAT pathway may contribute to the diabetogenic effect of CNIs but does not
      explain the stronger effect of TAC compared with CsA.

PMID- 28432719
TI  - Effect of Ficus carica leaf extract on the gene expression of selected factors in
      HaCaT cells.
AB  - BACKGROUND: Ficus carica Linn. (Fc), common fig, has been traditionally used for
      many metabolic, cardiovasculary, respiratory, gastrointestinal, and skin
      disorders. Several studies were performed showing its anti-inflammatory, anti
      angiogenic, anticancerogenic, and tissue-protective effects. In all of those
      studies, the positive effects of Fc were concluded as the result of its
      antioxidant and anti-inflammatory features due to the polyphenols it contains.
      AIMS: To study the phenolic compounds of Fc extract and to investigate the
      molecular basis of anti-inflammatory, anti-angiogenic, antimitotic, and anti
      androgenic effects of Fc leaf extract in vitro. MATERIALS AND METHODS: The gene
      expression levels of vascular endothelial growth factor (VEGF), tumor necrosis
      factor-alpha (TNF-a), interleukin 1-alpha (IL-1a), and 5 alpha-reductase type II
      (SRD5A2) were tested in human keratinocyte cells (HaCaT) by RT-qPCR. RESULTS: The
      gene expression analysis showed that the plant extract caused statistically
      significant downregulation of VEGF, TNF-a, IL-1a, and SRD5A2 compared to the
      untreated cells. DISCUSSION: These preliminary results of this in vitro study may
      partially explain the clinical success of Fc in the traditional medicine.
      CONCLUSION: Topical Fc leaf extract may be beneficial for some inflammatory
      disorders and androgen-dependent disorders of the skin such as androgenetic
      alopecia.

PMID- 28432720
TI  - Androgen receptor dysfunction as a prevalent manifestation in young male carriers
      of a FLNA gene mutation.
AB  - Androgenic actions require the proper signal transmission by the androgen
      receptor (AR), a nuclear transcription factor. This is initially located in the
      cell cytoplasm and should translocates to the nucleus to interact with DNA. AR
      functional impairment causes diverse blockage degrees of androgenic steroid
      action, known as androgen insensitivity syndromes. Filamin A, a protein coded by
      the FLNA gene, is a co-activator of various cytoplasmic factors, including AR.
      The mutational inactivation of the FLNA gene induces insufficiency of
      translocation and activation of AR. Consequently, it causes a developmental
      disorder of the male gonad and hypogonadism, similar to those observed in partial
      androgen insensitivity. We report two brothers carrying a loss-of-function
      mutation of FNLA with gonadal differentiation disorder and hypospadias. Specific
      staining for AR shows almost an absolute absence of these receptors in the
      testicular tissue. This association recommends investigating a possible
      mutational inactivation of the FLNA gene in patients with cryptorchidism and
      epididymo-testicular dissociation. The study is especially indicated when the
      family history, more often that of the mother, is suggestive. Likewise, growth
      and gonadal development of all male patients carrying this genetic trait should
      be monitored since childhood.

PMID- 28432721
TI  - Emollients and moisturizers for eczema: abridged Cochrane systematic review
      including GRADE assessments.
AB  - Eczema is a chronic inflammatory skin disorder with considerable impact on
      quality of life. Emollients or moisturizers are widely recommended, but are these
      effective and safe? We searched for randomized controlled trials (RCTs) in the
      Cochrane Skin Group Specialised Skin Register, CENTRAL in The Cochrane Library,
      MEDLINE, Embase, LILACS, the GREAT database and five trial registers to December
      2015. We included 77 RCTs with 6603 participants. Seven studies (9%) were at low
      risk of bias, 34 (44%) had unclear risk and 36 (47%) were at high risk. The
      quality of the evidence was mainly low or moderate for the prespecified outcomes.
      The most important comparison, 'moisturizer vs. no moisturizer', showed improved
      Scoring Atopic Dermatitis values in the moisturizer group compared with no
      moisturizer [mean difference -2.42, 95% confidence interval (CI) -4.55 to -0.28],
      but did not meet the minimal important difference of 8.7. Fewer flares were seen
      (risk ratio 0.40, 95% CI 0.23-0.70) and the rate of flares was reduced (hazard
      ratio 3.74, 95% CI 1.86-7.50). The groups applying moisturizer used less topical
      corticosteroids over 6-8 weeks (mean difference -9.30 g, 95% CI 15.3 to -3.27).
      Glycyrrhetinic acid-, urea- and glycerol-containing creams worked better than
      their controls (vehicle, placebo or no moisturizer) according to both
      participants and physicians. More flares were reported with moisturizer alone
      than when combined with twice-weekly fluticasone propionate (risk ratio 2.17, 95%
      CI 1.55-3.11). Adding moisturizers to topical anti-inflammatory treatment was
      more effective than anti-inflammatory treatment alone and resulted in fewer
      flares.

PMID- 28432722
TI  - Efforts to redefine endometriosis prevalence in low-risk patients.

PMID- 28432723
TI  - Comment: Kidney Exchange to Overcome Financial Barriers to Kidney
      Transplantation.

PMID- 28432724
TI  - Fluorescent Aerolysin (FLAER)-based paroxysmal nocturnal hemoglobinuria (PNH)
      screening: a single center experience from India.
AB  - BACKGROUND: Fluorescent aerolysin (FLAER) has been recommended as an important
      part of antibody panel used for flow cytometric detection of paroxysmal nocturnal
      hemoglobinuria (PNH) clone. This study was aimed to observe the frequency of PNH
      positive clones and their sizes in patients screened for various indications.
      METHOD: A retrospective analysis of 624 patients screened over a period of 30
      months. Frequency and size of clone sizes noted, and laboratory parameters were
      compared among different groups of patient being screened. RESULTS: There were
      445 adults and 179 pediatric patients. Indications for screening included AA (n =
      433), myelodysplastic syndrome (MDS) (n = 34), hemolytic anemia (n = 84), and
      thrombophilia workup group (n = 63). PNH clones were found in 39.03%, 5.88%,
      26.19%, and 1.59% cases, respectively. No significant difference among adult or
      pediatric population was noted. The bone marrow failure (BMF) group [AA and MDS]
      with PNH clone had a significantly lower clone size (Median- 2.7%) as compared to
      classic PNH group (Median-77.2%). Most of the classic PNH cases (78.26%) and a
      small proportion of AA (9.9%) showed a large clone size (>50%). In spite of
      having large clone size, there was a significant difference between the median
      LDH values of these two groups (2511.5 vs 593 U/L). CONCLUSION: FLAER-based
      screening detects the presence of PNH clone in a high proportion of AA patients
      and some MDS patients. These patients usually have a small clone size. Even if
      they have a large clone, it does not get translated into a high LDH or severe
      clinical symptoms.

PMID- 28432725
TI  - Synthesis and biological potency of anilino-triazine insecticides.
AB  - BACKGROUND: An insecticide screening effort identified N-(4-bromophenyl)-4,6
      bis(2,2,2-trifluoroethoxy)-1,3,5-triazine-2-amine as having weak potency against
      two lepidopteran species, Helicoverpa zea and Spodoptera exigua. A structure
      activity relationship study about the trifluoroethoxy substituents and the
      aniline of this compound was carried out in an effort to improve insecticidal
      potency. RESULTS: Initially, a series of analogs bearing various substituents on
      the aniline were prepared, and the insecticidal potency was evaluated against H.
      zea and S. exigua in greenhouse diet feeding assays. The results showed that
      electron-withdrawing substituents, such as Cl, Br and CF3 , were preferred over
      electron-donating substituents, such as methoxy, and that potency was
      significantly better when the substituent was in the para-position. Additional
      investigations showed that bis(anilino)trifluoroethoxytriazines were more potent.
      Replacement of the remaining trifluoroethyl group in the bis(anilino)triazine
      series with an alkyl amine lead to compounds of equal or superior efficacy.
      CONCLUSION: The work presented showed that electron-withdrawing substituents in
      the para-position of the aniline ring of the initial hit delivered the best
      levels of insecticidal potency against the two insect species tested. Further
      investigations showed that potency could be improved by replacing one of the two
      trifluoroethoxy groups with additional 4-substituted aniline. This level of
      potency was maintained or further improved when the remaining trifluoroethoxy was
      replaced with a substituted amine. (c) 2017 Society of Chemical Industry.

PMID- 28432727
TI  - Efficacy of fractionated microneedle radiofrequency with and without adding
      subcision for the treatment of atrophic facial acne scars: A randomized split
      face clinical study.
AB  - BACKGROUND: There is no gold standard treatment for facial acne scars, and
      overall, little literature exists about the combination therapy for treatment of
      acne scar. AIMS: The aim of this study was to evaluate the efficacy of
      fractionated microneedle radiofrequency (FMR) vs FMR combined with subcision for
      the treatment of atrophic acne scars. PATIENTS/METHODS: This was a randomized,
      split-face clinical study of 25 patients with II-IV Fitzpatrick skin types with
      moderate to severe facial atrophic acne scars. Initially, standard subcision by
      Nokor needle was performed on one side. Two weeks after subcision, FMR treatment
      was performed on both cheeks of each participant. Second and third FMR treatment
      sessions were performed within 4-week intervals. Two-blinded dermatologists
      performed clinical assessments using a quartile grading scale, and patients were
      also asked to judge their satisfaction using a visual analog scale (VAS) scoring
      system. RESULTS: The age of the patients varied from 24 to 40 years (mean:
      30.08+/-4.94 years). Only nine patients (36%) were males. Clinical assessment by
      two-blinded dermatologists showed statistically significant improvement in the
      combination (FMR+subcision) group (P=.009). Patient satisfaction was
      statistically significantly better in the combination group (P=.001). A darkening
      of skin phototype was associated with a decrease in patient's satisfaction VAS
      score (P=.07). CONCLUSION: The combination of subcision and FMR is a safe and
      effective modality for mixed type acne scars. Additional randomized clinical
      study with long-term follow-up is necessary for further evaluation of FMR in
      combination with other procedures. The full trial protocol can be accessed in:
      http://www.irct.ir/searchresult.php?keyword=%20%20IRCT2016103130597N1&id=30597&nu
      ber=1&field=a&prt=1&total=1&m=1. The clinical trial registration number is
      IRCT2016103130597N1.

PMID- 28432726
TI  - Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor.
AB  - The SGLT2 inhibitors (SGLTi) and glucagon-like-1 receptor agonists (GLP-1 RAs)
      effectively reduce HbA1c, but via very different mechanisms, making them an
      effective duet for combination therapy. Recently, drugs in both of these
      antidiabetic classes have been shown to reduce cardiovascular events, most
      probably by different mechanisms. SGLT2i appear to exert their CV protective
      actions by haemodynamic effects, while GLP-1 RAs work via anti-atherogenic/anti
      inflammatory mechanisms, raising the possibility that combined therapy with these
      2 classes may produce additive CV benefits. The SGLT2i and GLP-1 RAs also reduced
      macroalbuminuria, decreased the time for doubling of serum creatinine, and slowed
      the time to end-stage renal disease. In this perspective, we review the potential
      benefit of combination SGLT2i/GLP-1 RA therapy on metabolic-cardiovascular-renal
      disease in patients with type 2 diabetes mellitus.

PMID- 28432728
TI  - Expansion of the clinical phenotype of the distal 10q26.3 deletion syndrome to
      include ataxia and hyperemia of the hands and feet.
AB  - Distal deletion of the long arm of chromosome 10 is associated with a dysmorphic
      craniofacial appearance, microcephaly, behavioral issues, developmental delay,
      intellectual disability, and ocular, urogenital, and limb abnormalities. Herein,
      we present clinical, molecular, and cytogenetic investigations of four patients,
      including two siblings, with nearly identical terminal deletions of 10q26.3, all
      of whom have an atypical presentation of this syndrome. Their prominent features
      include ataxia, mild-to-moderate intellectual disability, and hyperemia of the
      hands and feet, and they do not display many of the other features commonly
      associated with deletions of this region. These results point to a novel gene
      locus associated with ataxia and highlight the variability of the clinical
      presentation of patients with deletions of this region.

PMID- 28432729
TI  - Novel amino acid ester-chlorantraniliprole conjugates: design, synthesis, phloem
      accumulation and bioactivity.
AB  - BACKGROUND: Conjugating amino acid and glucose fragments with existing pesticide
      structures has been shown to be an effective way to introduce phloem mobility
      into non-phloem mobile species. However, the resulting derivatives always suffer
      from lower bioactivity compared with their parent compound. To solve this
      problem, we designed and synthesised a series of ester-capped amino-acid
      conjugated chlorantraniliproles. RESULTS: The systemic test showed that all
      conjugates exhibited excellent phloem mobility and xylem mobility in a Ricinus
      communis model. In particular, compounds 7b, 8b and 8c were able to accumulate in
      phloem tissues in the form of their hydrolysis products, and the concentrations
      in phloem sap can reach 3 times the concentration in the incubation medium.
      Although their insecticidal activity (LC50 ) against the beet armyworm
      (Spodoptera exigua) in vitro was weaker than that of chlorantraniliprole,
      compounds 7b, 8b and 8c showed similar insecticidal activity in vivo against beet
      armyworm compared with the parent compound. CONCLUSIONS: This work provides a
      potential strategy to obtain pesticide derivatives that possess both improved
      uptake and improved mobility in crops while retaining the in vivo insecticidal
      effect of the parent compound. (c) 2017 Society of Chemical Industry.

PMID- 28432730
TI  - Assessment of voluntary deep inspiration breath-hold with CINE imaging for breast
      radiotherapy.
AB  - Deep Inspiration Breath-Hold (DIBH) techniques for breast cancer radiation
      therapy (RT) have reduced cardiac dose compared to Free Breathing (FB). Recently,
      a voluntary deep inspiration breath-hold (vDIBH) technique was established using
      in-room lasers and skin tattoos to monitor breath-hold. An in-house quality
      assessment of positional reproducibility during RT delivery with vDIBH in
      patients with left-sided breast cancer was evaluated. The electronic portal
      imaging device (EPID) was used in cinematographic (CINE) mode to capture a
      sequence of images during beam delivery. Weekly CINE images were retrospectively
      assessed for 20 left-sided breast cancer patients receiving RT in vDIBH, and
      compared with CINE images of 20 patients treated in FB. The intra-beam motion was
      assessed and the distance from the beam central axis (CA) to the internal chest
      wall (ICW) was measured on each CINE image. These were then compared to the
      planned distance on digitally reconstructed radiograph (DRR). The maximum intra
      beam motion for any one patient measurement was 0.30 cm for vDIBH and 0.20 cm for
      FB. The mean difference between the distance from the CA to ICW on DRR and the
      equivalent distance on CINE imaging (as treated) was 0.28 cm (SD 0.17) for vDIBH
      patients and 0.25 cm (SD 0.14) for FB patients (P = 0.458). The measured values
      were comparable for patients undergoing RT in vDIBH, and for those in FB. This
      quality assessment showed that using in-room lasers and skin tattoos to
      independently monitor breath-hold in vDIBH as detected by 'on-treatment' CINE
      imaging is safe and effective.

PMID- 28432731
TI  - Association between progressive hepatic morphology changes on serial MR imaging
      and clinical outcome in primary sclerosing cholangitis.
AB  - INTRODUCTION: Hepatic morphology changes are well described in Primary Sclerosing
      Cholangitis and characterised by a combination of atrophy and hypertrophy
      changes. This study investigates the relationship between progression of these
      changes over time and clinical outcome in patients with PSC. METHODS: Fifty-three
      patients with PSC (mean age 44, 28 males and 25 females) who underwent serial MRI
      liver studies at least one year apart were identified. The first and the last MRI
      studies were selected for the retrospective analysis. Three radiologists reviewed
      and compared both studies for changes in hepatic morphology, specifically atrophy
      and/or hypertrophy. The imaging findings were correlated with adverse clinical
      outcomes defined as death or liver transplantation and with serum bilirubin.
      RESULTS: There was a mean interval of 60 months between MRI examinations and a
      mean clinical follow-up period thereafter of 22 months. Thirty-three (62.3%)
      patients had stable hepatic morphology, whilst 20 (37.7%) patients showed hepatic
      morphology changes (atrophy: 13 patients, 24%; hypertrophy: 16 patients, 30%).
      Eleven patients (21%) died or underwent liver transplantation. There was a
      significant correlation between interval hepatic atrophy and adverse clinical
      outcomes (P = 0.001). Significant correlations were found between increasing
      serum bilirubin level and interval hepatic atrophy, hepatic hypertrophy and
      combined changes (P = 0.025, P = 0.022, P = 0.027, respectively). CONCLUSION:
      Hepatic morphology changes over time in patients with PSC are heterogeneous with
      some patients developing atrophy and/or hypertrophy whilst other patients remain
      stable. In this retrospective study, progressive hepatic atrophy showed
      significant association with adverse clinical outcome defined by either death or
      liver transplantation.

PMID- 28432732
TI  - Novel de novo FOXC1 nonsense mutation in an Axenfeld-Rieger syndrome patient.

PMID- 28432733
TI  - Variability in HbA1c, blood pressure, lipid parameters and serum uric acid, and
      risk of development of chronic kidney disease in type 2 diabetes.
AB  - AIM: Variability in HbA1c and blood pressure is associated with the risk of
      diabetic kidney disease (DKD). No evidence exists on the role of variability in
      lipids or serum uric acid (UA), or the interplay between the variability of
      different parameters, in renal outcomes. METHODS: Within the AMD Annals database,
      we identified patients with >=5 measurements of HbA1c, systolic blood pressure
      (SBP) and diastolic blood pressure (DBP), total-, high-density lipoprotein (HDL)-
      and low-density lipoprotein (LDL)-cholesterol, triglycerides, and UA. Patients
      were followed-up for up to 5 years. The impact of measures of variability on the
      risk of DKD was investigated by Cox regression analysis and recursive
      partitioning techniques. RESULTS: Four-thousand, two-hundred and thirty-one
      patients were evaluated for development of albuminuria, and 7560 for decreased
      estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m2 ). A significantly
      higher risk of developing albuminuria was associated with variability in HbA1c
      [upper quartile hazard ratio (HR) = 1.3; 95% confidence interval (CI) 1.1-1.6].
      Variability in SBP, DBP, HDL-C, LDL-C and UA predicted the decline in eGFR, the
      association with UA variability being particularly strong (upper quartile HR =
      1.8; 95% CI 1.3-2.4). The concomitance of high variability in HbA1c and HDL-C
      conferred the highest risk of developing albuminuria (HR = 1.47; 95% CI 1.17
      1.84), while a high variability in UA (HR = 1.54; 95% CI 1.19-1.99) or DBP (HR =
      1.47; 95% CI 1.11-1.94) conferred the highest risk of decline in eGFR.
      CONCLUSION: The variability of several parameters influences the development of
      DKD, having a different impact on albuminuria development and on the decline in
      GFR.

PMID- 28432735
TI  - Perinatal outcomes among young Indigenous Australian mothers: A cross-sectional
      study and comparison with adult Indigenous mothers.
AB  - BACKGROUND: The teenage pregnancy rate is high among Indigenous Australian women,
      yet little is known about their pregnancy outcomes. Moreover, against a
      background of extreme social disadvantage, the relative importance of age as a
      risk factor for adverse outcomes among Indigenous pregnancies is unclear. We
      compared perinatal outcomes for Indigenous teenagers (<20 years) with adult
      Indigenous women (20-34 years), and described outcomes in subgroups of teenagers.
      METHODS: Data were analyzed for 2421 singleton births to Indigenous women aged
      <35 years in Australia's Northern Territory from 2003 to 2005. Regression was
      used to assess the effect of young maternal age on normal birth, healthy baby,
      preterm birth, low birthweight, special care admission, and mean birthweight,
      adjusting for covariates. RESULTS: Three-quarters of teenagers and 62% of adult
      mothers lived in remote areas. Smoking rates were around 50% in both groups.
      Teenagers were more likely to have a normal birth than adults (adjusted odds
      ratio 1.78 [95% CI 1.35-2.34]). The groups did not differ for healthy baby,
      preterm birth, or low birthweight. Babies of teenagers weighed 135 g less than
      those of adults; however, adjustment for covariates eliminated this difference.
      Examination of teenage subgroups (<=16 years and 17-19 years) revealed risk
      behaviors being higher for 17-19 years olds than for the younger group, and more
      prevalent among urban-based mothers. DISCUSSION: Young maternal age is not a risk
      factor for adverse perinatal outcomes among Indigenous women. Rather, they are
      having babies in disadvantaged circumstances within a system challenged to
      support them socially and clinically.

PMID- 28432736
TI  - Severe primary autoimmune thrombocytopenia in pregnancy: a national cohort study.
AB  - OBJECTIVE: To quantify the incidence of severe autoimmune thrombocytopenia (ITP)
      in pregnancy in the UK, determine current treatment strategies, and establish
      maternal and neonatal morbidity and mortality associated with severe ITP in
      pregnancy. DESIGN: A prospective national cohort study. SETTING: UK. POPULATION:
      Women with severe ITP, defined as platelets <50 * 109 /L in pregnancy or
      antenatal treatment of isolated low platelets. METHODS: Data collected via the UK
      Obstetric Surveillance System (UKOSS) between 1 June 2013 and 31 January 2015
      from all UK consultant-led obstetric units. MAIN OUTCOME MEASURE: Incidence of
      severe ITP in pregnancy. RESULTS: The estimated incidence of severe ITP in
      pregnancy is 0.83 per 10 000 maternities (95% CI 0.68-1.00). A total of 22
      pregnant women (21%) did not receive any antenatal therapy, and 85 pregnant women
      (79%) received therapy. There was no difference between asymptomatic treated and
      untreated cohorts in severity of disease or outcome. Postpartum haemorrhage (51%)
      and severe postpartum haemorrhage (21%) was reported more frequently than the
      rate reported in the general pregnant population (5-10%). No neonates required
      treatment for thrombocytopenia and there were no cases of neonatal intracranial
      bleeding. CONCLUSIONS: Current UK management of severe ITP in pregnancy results
      in an exceptionally low morbidity and mortality for the neonate. Mothers with ITP
      remain at increased risk of severe postpartum haemorrhage, and should be
      delivered at units that have the capacity to manage severe PPH effectively.
      Whilst balancing the risks for pregnancy from prophylactic antenatal treatment in
      asymptomatic women against observed low disease morbidity, we may be over
      treating asymptomatic patients. TWEETABLE ABSTRACT: UKOSS study of severe ITP in
      pregnancy shows exceptionally low neonatal morbidity with current UK management.

PMID- 28432734
TI  - Monogenic diabetes syndromes: Locus-specific databases for Alstrom, Wolfram, and
      Thiamine-responsive megaloblastic anemia.
AB  - We developed a variant database for diabetes syndrome genes, using the Leiden
      Open Variation Database platform, containing observed phenotypes matched to the
      genetic variations. We populated it with 628 published disease-associated
      variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and
      SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alstrom, and Thiamine
      responsive megaloblastic anemia syndromes, respectively; and included 23
      previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1.
      We then investigated genotype-phenotype relations for the WFS1 gene. The presence
      of biallelic loss-of-function variants predicted Wolfram syndrome defined by
      insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI
      75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function
      variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated
      congenital cataracts without development of the full syndrome (sensitivity 100%
      [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic
      prediction based on genotype will lead to improvements in patient care and
      counseling. The development of the database as a repository for monogenic
      diabetes gene variants will allow prognostic predictions for other diabetes
      syndromes as next-generation sequencing expands the repertoire of genotypes and
      phenotypes. The database is publicly available online at https://lovd.euro
      wabb.org.

PMID- 28432737
TI  - Outcome reporting across randomised controlled trials evaluating therapeutic
      interventions for pre-eclampsia.
AB  - BACKGROUND: Standardising outcome collection and reporting in pre-eclampsia
      trials requires an appraisal of current outcome reporting. OBJECTIVES: To map
      maternal and offspring outcome reporting across randomised trials evaluating
      therapeutic interventions for pre-eclampsia. SEARCH STRATEGY: Randomised trials
      were identified by searching bibliographical databases from inception to January
      2016. SELECTION CRITERIA: Randomised controlled trials. DATA COLLECTION AND
      ANALYSIS: We systematically extracted and categorised outcome reporting. MAIN
      RESULTS: Seventy-nine randomised trials, reporting data from 31 615 maternal
      participants and 28 172 of their offspring, were included. Fifty-five different
      interventions were evaluated. Included trials reported 119 different outcomes,
      including 72 maternal outcomes and 47 offspring outcomes. Maternal outcomes were
      inconsistently reported across included trials; for example, 11 trials (14%)
      reported maternal mortality, reporting data from 12 422 participants, and 16
      trials (20%) reported cardiovascular morbidity, reporting data from 14 963
      maternal participants. Forty-three trials (54%) reported fetal outcomes and 23
      trials (29%) reported neonatal outcomes. Twenty-eight trials (35%) reported
      offspring mortality. There was poor reporting of childhood outcomes: six trials
      (8%) reported neurodevelopmental outcomes. Less than half of included trials
      reported any relevant information regarding harms for maternal participants and
      their offspring. CONCLUSIONS: Most randomised trials evaluating interventions for
      pre-eclampsia are missing information on clinically important outcomes, and in
      particular have neglected to evaluate efficacy and safety in the offspring of
      participants. Developing and implementing a minimum data set, known as a core
      outcome set, in future pre-eclampsia trials could help to address these issues.
      TWEETABLE ABSTRACT: Future #preeclampsia research requires a core outcome set to
      reduce #research waste. @coreoutcomes @jamesmnduffy International Prospective
      Register of Systematic Reviews: CRD42015015529;
      www.crd.york.ac.uk/PROSPERO/display_record.aspID=CRD42015015529.

PMID- 28432738
TI  - Tick bite and Lyme disease-related emergency department encounters in New
      Hampshire, 2010-2014.
AB  - Lyme disease (LD) is a common tick-borne disease in New Hampshire (NH). While LD
      is a reportable condition and cases are counted for public health surveillance,
      many more people receive care for tick bites or diagnoses of LD than are
      reflected in surveillance data. NH's emergency department (ED) data system was
      queried for tick bite and LD-related encounters. Chief complaint text was queried
      for words related to LD or tick bites. International Classification of Diseases
      9th Revision (ICD-9) codes were queried for the LD diagnosis code (088.81).
      Emergency department patient data were matched to reportable disease data to
      determine the proportion of ED patients reported to the health department as a
      suspected LD case. Data were analysed to calculate frequencies for key
      demographic and reporting characteristics. From 2010 to 2014, 13,615 tick bite or
      LD-related ED encounters were identified in NH, with most due to tick bites
      (76%). Of 3,256 patients with a LD-related ED encounter, 738 (23%) were reported
      to the health department as a suspected LD case. The geographic distribution of
      ED patients was similar to reported LD cases; however, the regions of the state
      that experienced higher rates of ED encounters were different than the regions
      that observed higher rates of reported LD cases. Seasonal distribution of ED
      encounters peaked earlier than reported LD cases with a second peak in the fall.
      While age and sex distribution was similar among ED patients and reported LD
      cases, the rates for children 5 years and younger and adults 65 years and older
      were greater for ED encounters. Patients frequently visit the ED to seek care for
      tick bites and suspected LD. Results of ED data analyses can be used to target
      education, in particular for ED providers and the public through timely
      distribution of evidence-based educational materials and training programmes.

PMID- 28432739
TI  - Effect of a 4-week elastic resistance band training regimen on back kinematics in
      horses trotting in-hand and on the lunge.
AB  - BACKGROUND: Training and rehabilitation techniques aiming at improving core
      muscle strength may result in increased dynamic stability of the equine vertebral
      column. A system of elastic resistance bands is suggested to provide
      proprioceptive feedback during motion to encourage recruitment of core abdominal
      and hindquarter musculature for improved dynamic stability. OBJECTIVES: To
      quantify the effects of a specific resistance band system on back kinematics
      during trot in-hand and lungeing at beginning and end of a 4-week exercise
      programme. STUDY DESIGN: Quantitative analysis of back movement before/after a 4
      week exercise programme. METHODS: Inertial sensor data were collected from seven
      horses at weeks 1 and 4 of an exercise protocol with elastic resistance bands.
      Translational (dorsoventral, mediolateral) and rotational (roll, pitch) range of
      motion of six landmarks from poll to coccygeal region were quantified during trot
      in-hand (hard surface) and during lungeing (soft surface, both reins)
      with/without elastic exercise bands. A mixed model (P<0.05) evaluated the effects
      of exercise bands, time (week) and movement direction (straight, left, right).
      RESULTS: The bands reduced roll, pitch and mediolateral displacement in the
      thoracolumbar region (all P<=0.04). At week 4, independent of band usage,
      rotational movement (withers, thoracic) was reduced while dorsoventral movement
      (thoracic, coccygeal) increased. Increased back movement was measured in 80% of
      back movement parameters during lungeing. MAIN LIMITATIONS: Comparing each horse
      without and with bands without a control group does not distinguish whether the
      differences measured between weeks 1 and 4 are related to use of the bands, or
      only to the exercise regimen. CONCLUSIONS: Results suggest that the elastic
      resistance bands reduce mediolateral and rotational movement of the thoracolumbar
      region (increase dynamic stability) in trot. Further studies should investigate
      the underlying mechanism with reference to core abdominal and hindquarter muscle
      recruitment and study the long-term effects. The Summary is available in Chinese 
      see Supporting Information.

PMID- 28432740
TI  - Novel 3q27.2-qter deletion in a patient with Diamond-Blackfan anemia and
      immunodeficiency: Case report and review of literature.
AB  - 3q27.2-qter deletion syndromes feature an overlapping set of terminal and
      interstitial deletions with variable congenital malformations. Diamond-Blackfan
      anemia (DBA) is etiologically heterogeneous disorder in which one cause is
      dominant mutations of the RPL35A gene on 3q29. We report a child with a 3q27.2
      qter deletion that contains the RPL35A gene. She had clinical and laboratory
      features consistent with DBA and as well, an unexplained immunodeficiency
      disorder. Given these unusual findings, we reviewed other patients in the
      literature with overlapping genomic deletions. In addition, we evaluated our
      patient for the immunodeficiency disorder, RIDDLE syndrome, due to recessive
      mutations in the RNF168 gene on 3q29. A PubMed search for case reports of 3q27.2
      qter overlapping deletions was performed. To determine if RPL35A was in the
      deletion region, the chromosomal regions reported were mapped to genomic regions
      using the UCSC Genome Browser. We identified 85 overlapping deletions, of which
      six included the RPL35A gene and all should be had DBA. Interestingly, none of
      the reported cases had immunodeficiency. To evaluate RIDDLE syndrome
      (radiosensitivity, immunodeficiency, dysmorphic features, and learning
      difficulties), we sequenced the remaining RNF168 gene and examined her fibroblast
      culture for a DNA double strand break repair deficiency. These results were
      normal, indicating that the immunodeficiency is unlikely to result from a RNF168
      deficiency. We show that RPL35A haploinsufficiency is a cause of DBA and we
      report a novel case with 3q27.2-qter deletion and immunodeficiency. The etiology
      for the immunodeficiency remains unsolved and could be caused by an unknown gene
      effect or consequent to the DBA phenotype.

PMID- 28432741
TI  - Pharmacokinetic and pharmacodynamic effects of two omeprazole formulations on
      stomach pH and gastric ulcer scores.
AB  - REASONS FOR PERFORMING THE STUDY: Limited data are available on the relative
      pharmacokinetics and pharmacodynamics of different omeprazole formulations.
      OBJECTIVES: To compare pharmacokinetic and pharmacodynamic effects of a novel
      omeprazole formulation against a currently registered product. STUDY DESIGN:
      Masked 2 period, 2 treatment crossover. METHODS: Twelve clinically healthy horses
      were studied over two 6-day treatment periods. Horses were randomly assigned to
      receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered
      reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h
      on the day prior to commencing treatment (Day -1) and after 6 days of oral
      treatment (Day 5) using in situ antimony pH probes within an indwelling
      nasogastric tube. Plasma pharmacokinetics were determined on Days 0 and 6.
      RESULTS: Treatment significantly (P<0.005) increased gastric pH on Day 5,
      compared to results obtained prior to treatment (Day -1) and there was no
      significant difference between products (P = 0.773). Similarly, comparison of
      median hourly gastric pH (P = 0.593), mean gastric pH (P = 0.154), percentage
      time pH<4 (P = 0.259) and area under the time-gastric pH response curve (P =
      0.734) did not discriminate between products. Both treatments resulted in
      significantly lower gastric ulcer severity scores (both P = 0.004), with no
      difference between treatments (P = 0.688). Comparison of mean log area under time
      plasma concentration curves demonstrated that, although the lower limit of the
      90% confidence interval was within the -20% limit for bioequivalence, the upper
      limit was exceeded, suggesting that the test product could have greater
      bioavailability than the reference product. MAIN LIMITATIONS: The small sample
      size, large interhorse plasma omeprazole concentrations, and low bioavailability
      of omeprazole impacted the sensitivity of the bioequivalence analysis.
      CONCLUSIONS: ULS matched or slightly exceeded OMO plasma concentrations. Both
      products resulted in equivalent increases in gastric pH, gastric pH profiles and
      decrease in gastric ulcer scores. Thus, ULS was pharmacodynamically equivalent to
      OMO and was associated with an equivalent beneficial effect on gastric squamous
      mucosal ulceration.

PMID- 28432742
TI  - Living Donor Uterus Transplantation: A Single Center's Observations and Lessons
      Learned From Early Setbacks to Technical Success.
AB  - Uterus transplantation is a vascularized composite allograft transplantation. It
      allows women who do not have a uterus to become pregnant and deliver a baby. In
      this paper, we analyze the first five cases of living donor uterus
      transplantation performed in the United States. The first three recipients lost
      their uterus grafts at days 14, 12, and 6, respectively, after transplant.
      Vascular complications, related to both inflow and outflow problems, were
      identified as the primary reason for the graft losses. Two recipients, at 6 and 3
      mo, respectively, after transplant, have functioning grafts with regular
      menstrual cycles. Ultimate success will be claimed only after a live birth. This
      paper is an in-depth analysis of evaluation, surgical technique, and follow-up of
      these five living donor uterus transplants. The lessons learned were instrumental
      in allowing us to evolve from failure to technical and functional success. We aim
      to share our conclusions and build on knowledge in the evolving field of uterus
      transplantation.

PMID- 28432743
TI  - Global and local visual processing in autism: An objective assessment approach.
AB  - We examined global and local visual processing in autism spectrum disorder (ASD)
      via a match-to-sample task using Kanizsa illusory contours (KIC). School-aged
      children with ASD (n = 28) and age-matched typically developing controls (n = 22;
      7-13 years) performed a sequential match-to-sample between a solid shape (sample)
      and two illusory alternatives. We tracked eye gaze and behavioral performance in
      two task conditions: one with and one without local interference from background
      noise elements. While analyses revealed lower accuracy and longer reaction time
      in ASD in the condition with local interference only, eye tracking robustly
      captured ASD-related global atypicalities across both conditions. Specifically,
      relative to controls, children with ASD showed decreased fixations to KIC
      centers, indicating reduced global perception. Notably, they did not differ from
      controls in regard to fixations to local elements or touch response location.
      These results indicate impaired global perception in the absence of heightened
      local processing in ASD. They also underscore the utility of eye-tracking
      measures as objective indices of global/local visual processing strategies in
      ASD. Autism Res 2017, 10: 1392-1404. (c) 2017 International Society for Autism
      Research, Wiley Periodicals, Inc.

PMID- 28432744
TI  - Kidney Paired-Donation Program Versus Global Kidney Exchange in India.

PMID- 28432745
TI  - Safety of sitagliptin in patients with type 2 diabetes and chronic kidney
      disease: outcomes from TECOS.
AB  - AIMS: To characterize the incidence of diabetes-associated complications and
      assess the safety of sitagliptin in participants with chronic kidney disease
      (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).
      MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14
      528), baseline characteristics and safety outcomes were compared for the CKD
      cohort (eGFR < 60 mL/min per 1.73 m2 ) vs those without CKD. Within the CKD
      cohort, the same analyses were performed, comparing sitagliptin- and placebo
      assigned participants. Baseline characteristics were summarized for all
      participants, and serious adverse events were analysed in those who received at
      least 1 dose of study medication. Adverse events of interest and diabetes
      complications were summarized for the intention-to-treat population. RESULTS: CKD
      was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for
      this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0)
      years, and 62% were men. Incidences of serious adverse events, malignancy, bone
      fracture, severe hypoglycaemia and most categories of diabetes complications were
      higher in the CKD cohort compared with those without CKD. Over ~2.8 median years
      of follow-up, CKD participants assigned to sitagliptin had rates of diabetic eye
      disease, diabetic neuropathy, renal failure, malignancy, bone fracture,
      pancreatitis and severe hypoglycaemia similar to those of placebo-assigned
      participants. CONCLUSIONS: Participants in TECOS with CKD had higher incidences
      of serious adverse events and diabetes complications than those without CKD.
      Treatment with sitagliptin was generally well tolerated, with no meaningful
      differences in safety outcomes observed between those with CKD assigned to
      sitagliptin or placebo.

PMID- 28432746
TI  - Impact of baseline glycated haemoglobin, diabetes duration and body mass index on
      clinical outcomes in the LixiLan-O trial testing a titratable fixed-ratio
      combination of insulin glargine/lixisenatide (iGlarLixi) vs insulin glargine and
      lixisenatide monocomponents.
AB  - To determine whether baseline characteristics had an impact on clinical outcomes
      in the LixiLan-O trial (N = 1170), we compared the efficacy and safety of
      iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U (iGlar)
      and lixisenatide (Lixi) with iGlar or Lixi alone in patients with uncontrolled
      type 2 diabetes mellitus (T2DM) on oral therapy. Subgroups according to baseline
      glycated haemoglobin (HbA1c; <8% or >=8% [<64 or >=64 mmol/mol]), T2DM disease
      duration (<7 or >=7 years) and body mass index (BMI; <30 or >=30 kg/m2 ) were
      investigated. In all subpopulations, iGlarLixi was consistently statistically
      superior to iGlar and Lixi alone in reducing HbA1c from baseline to week 30;
      higher proportions of patients achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi
      vs iGlar and Lixi alone. Compared with iGlar, iGlarLixi resulted in a substantial
      decrease in 2-hour postprandial plasma glucose levels, and mitigation of weight
      gain, with no differences among subpopulations in incidence of symptomatic
      hypoglycaemia. iGlarLixi consistently improved glycaemic control compared with
      iGlar and Lixi alone, without weight gain or increase in hypoglycaemic risk
      compared with iGlar in the subpopulations tested, regardless of baseline HbA1c,
      disease duration and BMI.

PMID- 28432747
TI  - Whole-body adipose tissue and lean muscle volumes and their distribution across
      gender and age: MR-derived normative values in a normal-weight Swiss population.
AB  - PURPOSE: To determine age- and gender-dependent whole-body adipose tissue and
      muscle volumes in healthy Swiss volunteers in Dixon MRI in comparison with
      anthropometric and bioelectrical impedance (BIA) measurements. METHODS: Fat-water
      separated whole-body 3 Tesla MRI of 80 healthy volunteers (ages 20 to 62 years)
      with a body mass index (BMI) of 17.5 to 26.2 kg/m2 (10 men, 10 women per decade).
      Age and gender-dependent volumes of total adipose tissue (TAT), visceral adipose
      tissue (VAT), total abdominal subcutaneous adipose tissue (ASAT) and total
      abdominal adipose tissue (TAAT), and the total lean muscle tissue (TLMT)
      normalized for body height were determined by semi-automatic segmentation, and
      correlated with anthropometric and BIA measurements as well as lifestyle
      parameters. RESULTS: The TAT, ASAT, VAT, and TLMT indexes (TATi, ASATi, VATi, and
      TLMTi, respectively) (L/m2  +/- standard deviation) for women/men were 6.4 +/-
      1.8/5.3 +/- 1.7, 1.6 +/- 0.7/1.2 +/- 0.5, 0.4 +/- 0.2/0.8 +/- 0.5, and 5.6 +/-
      0.6/7.1 +/- 0.7, respectively. The TATi correlated strongly with ASATi (r >
      0.93), VATi, BMI and BIA (r > 0.70), and TAATi (r > 0.96), and weak with TLMTi
      for both genders (r > -0.34). The VAT was the only parameter showing an age
      dependency (r > 0.32). The BMI and BIA showed strong correlation with all MR
      derived adipose tissue volumes. The TAT mass was estimated significantly lower
      from BIA than from MRI (both genders P < .001; mean bias -5 kg). CONCLUSIONS: The
      reported gender-specific MRI-based adipose tissue and muscle volumes might serve
      as normative values. The estimation of adipose tissue volumes was significantly
      lower from anthropometric and BIA measurements than from MRI. Magn Reson Med
      79:449-458, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 28432749
TI  - Motor nerve excitability after childhood Guillain-Barre syndrome.
AB  - Residual motor nerve dysfunction after pediatric Guillain-Barre syndrome (GBS)
      was determined in an observational cross-sectional cohort study in patients who
      previously developed GBS during childhood (<18 years). Ulnar motor nerve
      dysfunction was defined by compound motor action potential (CMAP) scan in
      patients after a follow up of at least 1 year compared with age-matched healthy
      controls, in relation to clinical course and outcome. A total of 37 persons
      previously diagnosed with GBS in childhood were included with a mean age at
      current examination of 20.6 years (4-39 years). The median time between diagnosis
      and follow-up was 11 years (range: 1-22 years). CMAP scanning indicated ulnar
      motor nerve dysfunction in 25 (68%) participants. The most frequent abnormality
      was a reduction in nerve excitability observed both in those with residual limb
      weakness and in the majority of those with complete recovery. CMAP scan
      characteristics were not related to prognostic factors or outcome. In conclusion,
      GBS in childhood results in residual motor nerve excitability disturbances, even
      in those completely recovered, probably reflecting altered physiology of
      regenerated peripheral nerves.

PMID- 28432748
TI  - Future challenges and therapeutic opportunities in type 2 diabetes: Changing the
      paradigm of current therapy.
AB  - Most algorithms for type 2 diabetes mellitus (T2DM) do not recommend treatment
      escalation until glycated haemoglobin (HbA1c) fails to reach the recommended
      target of 7% (53 mmol/mol) within approximately 3 months on any treatment regimen
      ("treat to failure"). Clinical inertia and/or poor adherence to therapy
      contribute to patients not reaching glycaemic targets when managed according to
      this paradigm. Clinical inertia exists across the entire spectrum of anti
      diabetes therapies, although it is most pronounced when initiating and optimizing
      insulin therapy. Possible reasons include needle aversion, fear of hypoglycaemia,
      excessive weight gain and/or the need for increased self-monitoring of blood
      glucose. Studies have suggested, however, that early intensive insulin therapy in
      newly diagnosed, symptomatic patients with T2DM with HbA1c >9% (75 mmol/mol) can
      preserve beta-cell function, thereby modulating the disease process. Furthermore,
      postprandial plasma glucose is a key component of residual dysglycaemia, evident
      especially when HbA1c remains above target despite fasting normoglycaemia.
      Therefore, to achieve near normoglycaemia, additional treatment with prandial
      insulin or a glucagon-like peptide-1 receptor agonist (GLP-1 RA) is often
      required. Long- or short-acting GLP-1 RAs offer effective alternatives to basal
      or prandial insulin in patients inadequately controlled with other therapies or
      basal insulin alone, respectively. This review highlights the limitations of
      current algorithms, and proposes an alternative based on the early introduction
      of insulin therapy and the rationale for the sequential or fixed combination of
      GLP-1 RAs with insulin ("treat-to-success" paradigm).

PMID- 28432750
TI  - Effects of feeding two RRR-alpha-tocopherol formulations on serum, cerebrospinal
      fluid and muscle alpha-tocopherol concentrations in horses with subclinical
      vitamin E deficiency.
AB  - BACKGROUND: Alpha-tocopherol (alpha-TP) supplementation is recommended for the
      prevention of various equine neuromuscular disorders. Formulations available
      include RRR-alpha-TP acetate powder and a more expensive but rapidly water
      dispersible liquid RRR-alpha-TP (WD RRR-alpha-TP). No cost-effective means of
      rapidly increasing serum and cerebrospinal fluid (CSF) alpha-TP with WD RRR-alpha
      TP and then sustaining concentrations with RRR-alpha-TP acetate has yet been
      reported. OBJECTIVES: To evaluate serum, CSF and muscle alpha-TP concentrations
      in an 8-week dosing regimen in which horses were transitioned from WD RRR-alpha
      TP to RRR-alpha-TP acetate. STUDY DESIGN: Non-randomised controlled trial.
      METHODS: Healthy horses with serum alpha-TP of <2 MUg/mL were divided into three
      groups and followed for 8 weeks. In the control group (n = 5), no alpha-TP was
      administered. In the second group (Group A; n = 7), 5000 IU/day RRR-alpha-TP
      acetate was administered. In the third group (Group WD-A; n = 7), doses of 5000
      IU/day of WD RRR-alpha-TP were administered over 3 weeks, followed by a 4-week
      transition from WD RRR-alpha-TP to RRR-alpha-TP acetate, and a final 1 week of
      treatment with RRR-alpha-TP acetate. Serum samples were obtained weekly; muscle
      biopsies were obtained before, at 2.5 weeks and after supplementation. CSF
      samples were obtained before and after the 8-week period of supplementation.
      RESULTS: Serum alpha-TP increased significantly in Group WD-A at week 1 and
      remained significantly higher than in Group A and the control group throughout
      the transition, with inter-individual variation in response. Serum alpha-TP
      increased significantly by week 7 in Group A. CSF alpha-TP increased
      significantly in Group WD-A only. Muscle alpha-TP concentrations did not differ
      significantly across groups. Serum and CSF alpha-TP were closely correlated (r =
      0.675), whereas serum and muscle-alpha-TP concentrations were not correlated.
      MAIN LIMITATIONS: The study duration was short and data on pre-transition CSF was
      lacking. CONCLUSIONS: The administration of 5000 IU/day of water-dispersible RRR
      alpha-TP rapidly increases serum alpha-TP. Serum and CSF alpha-TP concentrations
      are sustained with a gradual transition to 5000 IU/day of RRR-alpha-TP acetate.
      Periodic evaluation of serum alpha-TP concentrations is recommended because
      responses vary among individuals.

PMID- 28432751
TI  - Acute kidney injury, plasma lactate concentrations and lactic acidosis in
      metformin users: A GoDarts study.
AB  - AIMS: Metformin is renally excreted and has been associated with the development
      of lactic acidosis. Although current advice is to omit metformin during illnesses
      that may increase the risk of acute kidney injury (AKI), the evidence supporting
      this is lacking. We investigated the relationship between AKI, lactate
      concentrations and the risk of lactic acidosis in those exposed to metformin.
      MATERIALS AND METHODS: We undertook a population-based case-control study of
      lactic acidosis in 1746 participants with Type 2 diabetes and 846 individuals
      without diabetes with clinically measured lactates with and without AKI between
      1994 and 2014. AKI was stratified by severity according to "Kidney Disease:
      Improving Global Outcomes" guidelines. Mixed-effects logistic and linear
      regression were used to analyse lactic acidosis risk and lactate concentrations,
      respectively. RESULTS: Eighty-two cases of lactic acidosis were identified. In
      Type 2 diabetes, those treated with metformin had a greater incidence of lactic
      acidosis [45.7 per 100 000 patient years; 95% confidence interval (CI) 35.9-58.3]
      compared to those not exposed to this drug (11.8 per 100 000 patient years; 95%
      CI 4.9-28.5). Lactate concentrations were 0.34 mmol/L higher in the metformin
      exposed cohort (P < .001). The risk of lactic acidosis was higher in metformin
      users [odds ratio (OR) 2.3; P = .002] and increased with AKI severity (stage 1:
      OR 3.0, P = .002; stage 2: OR 9.4, P < .001; stage 3: OR 16.1, P < .001).
      CONCLUSIONS: A clear association was found between metformin, lactate
      accumulation and the development of lactic acidosis. This relationship is
      strongest in those with AKI. These results provide robust evidence to support
      current recommendations to omit metformin in any illness that may precipitate
      AKI.

PMID- 28432752
TI  - Incretin-based glucose-lowering medications and the risk of acute pancreatitis
      and/or pancreatic cancer: Reassuring data from cardio-vascular outcome trials.

PMID- 28432753
TI  - Identification of indothiazinone as a natural antiplatelet agent.
AB  - Cardiovascular disease, which is caused by unregulated platelet aggregation, is
      one of the main causes of deaths worldwide. Many studies have focused on natural
      products with antiplatelet effects as a safe alternative therapy to prevent the
      disease. In this context, an in-house chemical library was screened to find
      natural products capable of inhibiting the interaction between platelet integrin
      alphaIIbbeta3 and fibrinogen, which is an essential step in platelet aggregation.
      On the basis of the screening results, indothiazinone, an alkaloid found in
      microbial cultures, was identified as a potential antiplatelet agent.
      Specifically, indothiazinone treatment significantly inhibited the binding of
      fibrinogen to Chinese hamster ovary cells expressing integrin alphaIIbbeta3. It
      also restricted thrombin- and adenosine diphosphate-dependent spreading of human
      platelets on a fibrinogen matrix. More importantly, surface plasmon resonance and
      molecular dynamics studies suggested that indothiazinone suppressed talin-induced
      activation of integrin alphaIIbbeta3 presumably by inhibiting talin-integrin
      interaction. In conclusion, these results suggest that indothiazinone can be used
      as a lead compound for the development of antiplatelet drugs with a novel mode of
      action.

PMID- 28432754
TI  - Intraclass differences in the risk of hospitalization for heart failure among
      patients with type 2 diabetes initiating a dipeptidyl peptidase-4 inhibitor or a
      sulphonylurea: Results from the OsMed Health-DB registry.
AB  - AIMS: To re-analyse data from a previous retrospective study on 127 555 patients,
      in which we showed that dipeptidyl peptidase-4 (DPP-4) inhibitor therapy was
      associated with a lower risk of hospitalization for HF (HHF) than sulphonylurea
      (SU) therapy, in order to evaluate intraclass differences among DPP-4 inhibitors
      and SUs. METHODS: We included patients with type 2 diabetes (T2D) initiating DPP
      4 inhibitor or SU therapy, alone or in combination with metformin. Patients
      undergoing intraclass switch, those with a previous HHF, those receiving insulin
      treatment, and those with <6 months observation were excluded. We calculated the
      incidence of first and total HHF events/1000 person-years. Cox proportional
      hazard and Poisson multiple regression models, as well as propensity-score
      matching, were used to account for baseline confounders. RESULTS: The analysis
      included 17 615 DPP-4 inhibitor users (60.1% sitagliptin; 27.0% vildagliptin;
      12.9% saxagliptin) and 86 734 SU users (37.5% glibenclamide; 34.6% glimepiride;
      27.9% gliclazide). No intraclass difference in the incidence rate of first and
      total HHF events was noted among the 3 DPP-4 inhibitors or among the 3 SUs.
      Multivariable adjustments for baseline confounders or propensity-score matching
      did not change the results. In addition, no intraclass difference in HHF risk was
      observed in patients at high compared with low cardiovascular risk. CONCLUSIONS:
      In a cohort of patients with T2D taken from approximately one-third of the
      Italian population, no intraclass difference was noted for DPP-4 inhibitor and SU
      therapy with regard to HHF risk.

PMID- 28432756
TI  - High rate of systemic corticosteroid prescription among outpatient visits for
      psoriasis: A population-based epidemiological study using the Korean National
      Health Insurance database.
AB  - The use of systemic corticosteroids (SC) for the treatment of psoriasis is not
      recommended according to textbooks and guidelines. In clinical practise, however,
      many physicians frequently prescribe SC for patients with psoriasis. To determine
      the magnitude of SC prescription for outpatients with psoriasis in Korea and
      identify factors associated with the use of SC, we used the 2010-2014 nationwide
      claims data of the Health Insurance Review and Assessment Service of Korea. In
      frequency analysis for the full scale of prescribed SC, oral methylprednisolone
      was the most frequently prescribed SC, followed by dexamethasone and
      betamethasone injections. The prescription rate of SC was 26.4% in outpatient
      visit episodes for psoriasis. The prescription rate of SC was higher in older
      patients, Medical Aid recipients, patients who visited office-based physician
      practices and hospitals, and patients living in non-metropolitan areas. In
      multiple logistic regression analyses, the older age group and smaller health
      care institutions were more associated with the SC prescription. In conclusion,
      SC were widely prescribed for patients with psoriasis in Korea despite the
      current guidelines. Both patients' individual and institutional characteristics
      were associated with the SC prescription.

PMID- 28432758
TI  - Specificity and sensitivity of magnetic resonance imaging findings in the
      diagnosis of progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative condition that can
      only be diagnosed conclusively on pathological examination. Currently, the
      diagnosis is based upon the National Institute of Neurological Disorders and
      Stroke and the Society for PSP criteria. These criteria consist of purely
      clinical findings. Elements of brain MRI that are being investigated for this
      role include identifying structural features on conventional MRI, volume changes,
      signal abnormalities and diffusion changes. The aim of this study is to conduct a
      systematic search to identify which MRI findings have evidence to support their
      sensitivity/specificity/accuracy in the diagnosis of PSP. A search was conducted
      of Pubmed and Medline on July 5th-6th 2016 using the medical subject headings
      progressive supranuclear palsy and MRI. Seventy articles were identified which
      assessed the sensitivity/specificity/accuracy of MRI signs for the diagnosis of
      PSP. There were 13 studies that identified MRI features that had >=95%
      sensitivity and specificity for the diagnosis of PSP. Four of these studies
      identified the magnetic resonance parkinsonism index as highly sensitive and
      specific. There were only four studies which assessed how effective given MRI
      features are at predicting the pathological diagnosis of PSP. Several markers,
      such as the magnetic resonance parkinsonism index, have been demonstrated to be
      both specific and sensitive for PSP. However, many studies assessing these
      markers have common weaknesses including small sample size and lacking autopsy
      correlation.

PMID- 28432757
TI  - Headache patients' satisfaction with telemedicine: a 12-month follow-up
      randomized non-inferiority trial.
AB  - BACKGROUND AND PURPOSE: We investigated non-acute headache patients' long-term
      satisfaction with a telemedicine consultation and consultation preferences in
      northern Norway. We hypothesized that patients were not less satisfied with
      telemedicine than traditional consultations. We also examined the influence of
      gender, age and education on satisfaction. METHODS: For 2.5 years, patients were
      consecutively screened, recruited and randomly assigned to telemedicine or
      traditional visits with a consultation at a neurological outpatient department.
      The primary endpoint was frequency of satisfied patients at 3 and 12 months.
      Secondary endpoints were satisfaction with consultation, communication,
      information, diagnosis, advice and prescriptions, and preferred visit form at 12
      months. RESULTS: Of 402 participants, 279 (69.4%) answered questionnaires at both
      3 and 12 month, and 291 (72.4%) responded at 12 months. The long-term
      satisfaction of telemedicine patients was 124/145 (85.5%) compared with 118/134
      (88.1%) in the traditional group (P = 0.653). The groups did not differ with
      respect to secondary endpoints, but females were more satisfied with telemedicine
      communication (P = 0.027). In the telemedicine group, 99/147 (67.3%) were
      indifferent to the type of consultation. Age and education did not alter the
      primary results. CONCLUSIONS: At 1 year after a specialist evaluation for
      headache, telemedicine patients did not express less satisfaction than those with
      traditional consultation. Telemedicine specialist consultations may be a good
      alternative for headache patients in secondary care.

PMID- 28432759
TI  - Anesthetic and Postanesthetic Effects of Alfaxalone-Butorphanol Compared with
      Dexmedetomidine-Ketamine in Chinchillas (Chinchilla lanigera).
AB  - Effective and safe anesthetic protocols are required for a variety of surgical
      and diagnostic procedures in chinchillas.Alfaxalone, a new anesthetic agent in
      the United States, can be administered intramuscularly and subcutaneously and is
      therefore potentially useful as an anesthetic induction agent in chinchillas.
      This study compared the anesthetic efficacy andpostanesthetic effects on food
      intake and fecal output of a combination of intramuscular alfaxalone (5 mg/kg)
      and butorphanol(0.5 mg/kg; AB anesthesia) with a combination of dexmedetomidine
      (0.015 mg/kg) and ketamine (4 mg/kg; DK anesthesia) in a blinded, randomized,
      complete crossover design in chinchillas (n = 12). The AB combination resulted in
      a rapid induction of short-term anesthesia, which was inconsistent in depth and
      length. In contrast, the DK protocol resulted in rapid induction of a consistent
      level surgical anesthesia and rapid recovery after administration of atipamezole
      (0.15 mg/kg IM). Food intake and fecal output were significantly more decreased
      in the AB group (food, -65.9% +/- 17.7%; feces, -72.2% +/- 18.7%) than in the DK
      group (food: -37.7% +/- 8.2%, feces: -16.5% +/- 15.8%) during the first 24 h
      after anesthesia. Food intake and fecal output remained significantly reduced
      compared with preanesthetic levels for 4 to 5 d after anesthesia with both
      protocols. Compared with the AB protocol, the DK protocol provided superior
      anesthetic efficacy and had fewer postanesthetic side effects in chinchillas and
      is therefore a more suitable injectable anesthetic combination for this species.

PMID- 28432760
TI  - Determination of Ochratoxin A in Black and White Pepper, Nutmeg, Spice Mix,
      Cocoa, and Drinking Chocolate by High-Performance Liquid Chromatography Coupled
      with Fluorescence Detection: Collaborative Study.
AB  - A method validation study for the determination of ochratoxin A in black and
      white pepper (Piper spp.), nutmeg (Myristica fragrans), spice mix (blend of
      ginger, turmeric, pepper, nutmeg, and chili), cocoa powder, and drinking
      chocolate was conducted according to the International Harmonized Protocol of the
      International Union of Pure and Applied Chemistry. The method is based on the
      extraction of samples with aqueous methanol, followed by a cleanup of the extract
      with an immunoaffinity column. The determination is carried out by reversed-phase
      LC coupled with a fluorescence detector. The study involved 25 participants
      representing a cross-section of research, private, and official control
      laboratories from 12 European Union (EU) Member States, together with Turkey and
      Macedonia. Mean recoveries ranged from 71 to 85% for spices and from 85 to 88%
      for cocoa and drinking chocolate. The RSDr values ranged from 5.6 to 16.7% for
      spices and from 4.5 to 18.7% for cocoa and drinking chocolate. The RSDR values
      ranged from 9.5 to 22.6% for spices and from 13.7 to 30.7% for cocoa and drinking
      chocolate. The resulting Horwitz ratios ranged from 0.4 to 1 for spices and from
      0.6 to 1.4 for cocoa and drinking chocolate according to the Horwitz function
      modified by Thompson. The method showed acceptable within-laboratory and between
      laboratory precision for each matrix, and it conforms to requirements set by
      current EU legislation.

PMID- 28432755
TI  - Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue.
AB  - Age is the most important risk factor for most diseases. Mitochondria play a
      central role in bioenergetics and metabolism. In addition, several lines of
      evidence indicate the impact of mitochondria in lifespan determination and
      ageing. The best-known hypothesis to explain ageing is the free radical theory,
      which proposes that cells, organs, and organisms age because they accumulate
      reactive oxygen species (ROS) damage over time. Mitochondria play a central role
      as the principle source of intracellular ROS, which are mainly formed at the
      level of complex I and III of the respiratory chain. Dysfunctional mitochondria
      generating less ATP have been observed in various aged organs. Mitochondrial
      dysfunction comprises different features including reduced mitochondrial content,
      altered mitochondrial morphology, reduced activity of the complexes of the
      electron transport chain, opening of the mitochondrial permeability transition
      pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial
      quality control or defects in mitochondrial dynamics have also been linked to
      senescence. Among the tissues affected by mitochondrial dysfunction are those
      with a high-energy demand and thus high mitochondrial content. Therefore, the
      present review focuses on the impact of mitochondria in the ageing process of
      heart and skeletal muscle. In this article, we review different aspects of
      mitochondrial dysfunction and discuss potential therapeutic strategies to improve
      mitochondrial function. Finally, novel aspects of adipose tissue biology and
      their involvement in the ageing process are discussed.

PMID- 28432762
TI  - Microvascular replantation of head and neck amputated parts: A systematic review.
AB  - BACKGROUND: As opposed to upper and lower extremity amputations representing a
      considerable volume of admissions, the prowess of microsurgeons is seldom
      solicited in complex cases of head and neck replantation. Our aim was to
      determine the rate of successful replantation of craniofacial parts in a
      systematic review of the literature. METHODS: We performed a systematic review of
      English literature using PubMed/MEDLINE for every replantation of a head and neck
      parts. Articles selected for analysis required to describe microvascular surgical
      techniques to be considered a replantation. The measured endpoint for a
      successful replantation was survival at hospital discharge. RESULTS: From 113
      articles from the literature, reported cases of replanted craniofacial parts
      included 90 scalps, 56 ears, 34 lips, 26 noses, 1 eyebrow, and 1 midface. A
      significant majority of amputations were described as an avulsion mechanism
      (78.4%), as opposed to cutting/sharp (17.3%) or crush-type (1.9%). The overall
      success rate at hospital discharge was 72.1%, with a partial failure at 20.2% and
      a complete failure at 7.7%. CONCLUSION: Urgent replantation of head and neck
      amputated parts allow patients to recover in a timely manner and to decrease the
      need for secondary reconstructive procedures. The significant rate of success is
      a strong argument in favor of promoting access to care for replantation of
      craniofacial parts.

PMID- 28432761
TI  - Protein S-sulfhydration by hydrogen sulfide in cardiovascular system.
AB  - : Hydrogen sulfide (H2 S), independently of any specific transporters, has a
      number of biological effects on the cardiovascular system. However, until now,
      the detailed mechanism of H2 S was not clear. Recently, a novel post
      translational modification induced by H2 S, named S-sulfhydration, has been
      proposed. S-sulfhydration is the chemical modification of specific cysteine
      residues of target proteins by H2 S. There are several methods for detecting S
      sulfhydration, such as the modified biotin switch assay, maleimide assay with
      fluorescent thiol modifying regents, tag-switch method and mass spectrometry. H2
      S induces S-sulfhydration on enzymes or receptors (such as p66Shc, phospholamban,
      protein tyrosine phosphatase 1B, mitogen-activated extracellular signal-regulated
      kinase 1 and ATP synthase subunit alpha), transcription factors (such as specific
      protein-1, kelch-like ECH-associating protein 1, NF-kappaB and interferon
      regulatory factor-1), and ion channels (such as voltage-activated Ca2+ channels,
      transient receptor potential channels and ATP-sensitive K+ channels) in the
      cardiovascular system. Although significant progress has been achieved in
      delineating the role of protein S-sulfhydration by H2 S in the cardiovascular
      system, more proteins with detailed cysteine sites of S-sulfhydration as well as
      physiological function need to be investigated in further studies. This review
      mainly summarizes the role and possible mechanism of S-sulfhydration in the
      cardiovascular system. The S-sulfhydrated proteins may be potential novel targets
      for therapeutic intervention and drug design in the cardiovascular system, which
      may accelerate the development and application of H2 S-related drugs in the
      future. LINKED ARTICLES: This article is part of a themed section on Spotlight on
      Small Molecules in Cardiovascular Diseases. To view the other articles in this
      section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

PMID- 28432764
TI  - Small-Molecule Anion Recognition by a Shape-Responsive Bowl-Type Dodecavanadate.
AB  - A dodecavanadate, [V12 O32 ]4- , is an inorganic bowl-type host with a cavity
      entrance with a diameter of 4.4 A in the optimized structure. Linear, bent, and
      trigonal planar anions are tested as guest anions and the formation of host-guest
      complexes, [V12 O32 (X)]5- (X=CN- , OCN- , NO2- , NO3- , HCO2- , and CH3 CO2- ),
      were confirmed by X-ray crystallographic analyses and a 51 V NMR spectroscopy
      study. The degree of distortion of the bowl from a regular to an oval shape
      depends on the type of guest anion. In 51 V NMR spectroscopy, all chemical shifts
      of the host-guest complexes are clearly shifted after guest incorporation. The
      incorporation reaction rates for OCN- , NO2- , HCO2- , and CH3 CO2- are much
      larger than those of NO3- and halides. The incorporated nonspherical molecular
      anions in the dodecavanadate host are easily dissociated or exchanged for other
      anions, whereas spherical halides in the host are preserved without dissociation,
      even in the presence of the tested anions.

PMID- 28432763
TI  - Multiple strong postmating and intrinsic postzygotic reproductive barriers
      isolate florally diverse species of Jaltomata (Solanaceae).
AB  - Divergence in phenotypic traits often contributes to premating isolation between
      lineages, but could also promote isolation at postmating stages. Phenotypic
      differences could directly result in mechanical isolation or hybrids with
      maladapted traits; alternatively, when alleles controlling these trait
      differences pleiotropically affect other components of development,
      differentiation could indirectly produce genetic incompatibilities in hybrids.
      Here, we determined the strength of nine postmating and intrinsic postzygotic
      reproductive barriers among 10 species of Jaltomata (Solanaceae), including
      species with highly divergent floral traits. To evaluate the relative importance
      of floral trait diversification for the strength of these postmating barriers, we
      assessed their relationship to floral divergence, genetic distance, geographical
      context, and ecological differences, using conventional tests and a new linear
      mixed modeling approach. Despite close evolutionary relationships, all species
      pairs showed moderate to strong isolation. Nonetheless, floral trait divergence
      was not a consistent predictor of the strength of isolation; instead this was
      best explained by genetic distance, although we found evidence for mechanical
      isolation in one species, and a positive relationship between floral trait
      divergence and fruit set isolation across species pairs. Overall, our data
      indicate that intrinsic postzygotic isolation is more strongly associated with
      genome-wide genetic differentiation, rather than floral divergence.

PMID- 28432765
TI  - Nature's Parkin experiment: Nix-a novel protective mechanism in Parkinson's
      disease.

PMID- 28432766
TI  - 2017 ACR/ARHP Pediatric Rheumatology Symposium.
AB  - For a searchable version of these abstracts, please visit www.acrabstracts.org.

PMID- 28432767
TI  - Categorical learning revealed in activity pattern of left fusiform cortex.
AB  - The brain is organized such that it encodes and maintains category information
      about thousands of objects. However, how learning shapes these neural
      representations of object categories is unknown. The present study focuses on
      faces, examining whether: (1) Enhanced categorical discrimination or (2) Feature
      analysis enhances face/non-face categorization in the brain. Stimuli ranged from
      non-faces to faces with two-toned Mooney images used for testing and gray-scale
      images used for training. The stimulus set was specifically chosen because it has
      a true categorical boundary between faces and non-faces but the stimuli
      surrounding that boundary have very similar features, making the boundary harder
      to learn. Brain responses were measured using functional magnetic resonance
      imaging while participants categorized the stimuli before and after training.
      Participants were either trained with a categorization task, or with non
      categorical semblance analyzation. Interestingly, when participants were
      categorically trained, the neural activity pattern in the left fusiform gyrus
      shifted from a graded representation of the stimuli to a categorical
      representation. This corresponded with categorical face/non-face discrimination,
      critically including both an increase in selectivity to faces and a decrease in
      false alarm response to non-faces. By contrast, while activity pattern in the
      right fusiform cortex correlated with face/non-face categorization prior to
      training, it was not affected by learning. Our results reveal the key role of the
      left fusiform cortex in learning face categorization. Given the known right
      hemisphere dominance for face-selective responses, our results suggest a rethink
      of the relationship between the two hemispheres in face/non-face categorization.
      Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28432768
TI  - The fate of recently fixed carbon after drought release: towards unravelling C
      storage regulation in Tilia platyphyllos and Pinus sylvestris.
AB  - Carbon reserves are important for maintaining tree function during and after
      stress. Increasing tree mortality driven by drought globally has renewed the
      interest in how plants regulate allocation of recently fixed C to reserve
      formation. Three-year-old seedlings of two species (Tilia platyphyllos and Pinus
      sylvestris) were exposed to two intensities of experimental drought during ~10
      weeks, and 13 C pulse labelling was subsequently applied with rewetting. Tracking
      the 13 C label across different organs and C compounds (soluble sugars, starch,
      myo-inositol, lipids and cellulose), together with the monitoring of gas exchange
      and C mass balances over time, allowed for the identification of variations in C
      allocation priorities and tree C balances that are associated with drought
      effects and subsequent drought release. The results demonstrate that soluble
      sugars accumulated in P. sylvestris under drought conditions independently of
      growth trends; thus, non-structural carbohydrates (NSC) formation cannot be
      simply considered a passive overflow process in this species. Once drought
      ceased, C allocation to storage was still prioritized at the expense of growth,
      which suggested the presence of 'drought memory effects', possibly to ensure
      future growth and survival. On the contrary, NSC and growth dynamics in T.
      platyphyllos were consistent with a passive (overflow) view of NSC formation.

PMID- 28432769
TI  - Pocketable ultrasonography for bedside flap monitoring.

PMID- 28432770
TI  - Chiral separation of aryloxyphenoxy-propionate herbicides in a permethyl-beta
      cyclodextrin based column. Influence of temperature and mobile phase composition
      on enantioselectivity.
AB  - We used a permethyl-beta-cyclodextrin chiral stationary phase under reversed
      phase conditions for the chiral separation of four aryloxyphenoxy-propionate
      herbicides (fenoxaprop-p-ethyl, quizalofop-p-ethyl and tefuryl, and haloxyfop-p
      methyl) with mixtures of methanol, ethanol, 2-propanol, n-propanol, tert-butanol,
      or acetonitrile and water as mobile phases and investigated the influence of
      mobile phase composition and column temperature (from 0 to 50 degrees C) on the
      separation. The retention factors (k) and selectivity factors (alpha) of all the
      herbicides investigated decreased with increasing temperature. The lnalpha versus
      1/T and lnk versus 1/T plots for the enantiomers of the chiral pesticides were
      linear within the range of 0-50 degrees C with all alcohol/water mixtures
      constituting the mobile phase, but the lnk versus 1/T plots were nonlinear for
      all the enantiomers chromatographed in acetonitrile/water mixtures. The
      thermodynamic parameters based on linear van't Hoff plots were calculated. The
      influence of temperature and mobile phase composition on the enantioseparation of
      the solutes has rarely been considered simultaneously. The temperature and the
      solvents used in the mobile phase, however, were found to have a profound effect
      on the enantioseparation of these herbicides.

PMID- 28432771
TI  - A rare variant in TOR1A exon 5 associated with isolated dystonia in southwestern
      Chinese.
AB  - BACKGROUND: TOR1A has been proposed as an important genetic factor in early-onset
      isolated dystonia. Variants located in the 3' untranslated region of TOR1A are of
      particular importance because they may influence gene expression, although
      related studies are limited. The objectives of the present study focused on
      variants in the TOR1A 3' untranslated region. METHODS: The last exon of TOR1A was
      sequenced in 229 cases with isolated dystonia and in 210 controls. In addition,
      471 controls were tested to determine the frequency of the variants in the 3'
      untranslated region. RESULTS: Except for c.904_906delGAG, 3 rare sequence
      variants (NM_000113.2:c.*454T>A, NM_000113.2:c.860C>A [rs766483672], and
      NM_000113.2:c.*302T>A [rs563498119]) were found only in the patients. The
      c.*302T>A variant was located in the conserved region of the human microRNA (hsa
      miR-494) binding site. A luciferase reporter assay showed that c.*302T>A
      significantly altered gene expression. CONCLUSIONS: Population frequencies,
      computational analyses, and function experiments in this study implied that
      c.*302T>A is associated with dystonia. (c) 2017 International Parkinson and
      Movement Disorder Society.

PMID- 28432772
TI  - Studies on the chitin/chitosan binding properties of six cuticular proteins
      analogous to peritrophin 3 from Bombyx mori.
AB  - Chitin deacetylation is required to make the cuticle rigid and compact through
      chitin chain crosslinking. Thus it is presumed that specialized proteins are
      required to bind deacetylated chitin chains together. However, deacetylated
      chitin binding proteins have not ever been reported. In a previous work, six
      cuticular proteins analogous to peritrophin 3 (CPAP3s) were found to be abundant
      in the moulting fluid of Bombyx mori. In this study, these BmCPAP3s (BmCPAP3-A1,
      BmCPAP3-A2, BmCPAP3-B, BmCPAP3-C, BmCPAP3-D1 and BmCPAP3-D2) were cloned and
      expressed in Escherichia coli and purified using metal-chelating affinity
      chromatography. Their binding activities demonstrated that although all of the
      BmCPAP3s showed similar binding abilities toward crystalline chitin and colloidal
      chitin, they differed in their affinities toward partially and fully deacetylated
      chitin. Amongst them, BmCPAP3-D1 exhibited the highest binding activity toward
      deacetylated chitin. The gene expression pattern of BmCPAP3-D1 was similar to
      BmCPAP3-A1 and BmCPAP3-C at most stages except that it was dramatically
      upregulated at the beginning of the pupa to adult transition stage. This work is
      the first report of a chitin-binding protein, BmCPAP3-D1, which exhibits high
      binding affinity to deacetylated chitin.

PMID- 28432773
TI  - Transition of the functional brain network related to increasing cognitive
      demands.
AB  - : Network neuroscience provides tools that can easily be used to verify main
      assumptions of the global workspace theory (GWT), such as the existence of highly
      segregated information processing during effortless tasks performance, engagement
      of multiple distributed networks during effortful tasks and the critical role of
      long-range connections in workspace formation. A number of studies support the
      assumptions of GWT by showing the reorganization of the whole-brain functional
      network during cognitive task performance; however, the involvement of specific
      large scale networks in the formation of workspace is still not well-understood.
      THE AIMS OF OUR STUDY WERE: (1) to examine changes in the whole-brain functional
      network under increased cognitive demands of working memory during an n-back
      task, and their relationship with behavioral outcomes; and (2) to provide a
      comprehensive description of local changes that may be involved in the formation
      of the global workspace, using hub detection and network-based statistic. Our
      results show that network modularity decreased with increasing cognitive demands,
      and this change allowed us to predict behavioral performance. The number of
      connector hubs increased, whereas the number of provincial hubs decreased when
      the task became more demanding. We also found that the default mode network (DMN)
      increased its connectivity to other networks while decreasing connectivity
      between its own regions. These results, apart from replicating previous findings,
      provide a valuable insight into the mechanisms of the formation of the global
      workspace, highlighting the role of the DMN in the processes of network
      integration. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28432774
TI  - Comprehensive two-dimensional PC-3 prostate cancer cell membrane chromatography
      for screening anti-tumor components from Radix Sophorae flavescentis.
AB  - Radix Sophorae flavescentis is generally used for the treatment of different
      stages of prostate cancer in China. It has ideal effects when combined with
      surgical treatment and chemotherapy. However, its active components are still
      ambiguous. We devised a comprehensive two-dimensional PC-3 prostate cancer cell
      membrane chromatography system for screening anti-prostate cancer components in
      Radix Sophorae flavescentis. Gefitinib and dexamethasone were chosen as positive
      and negative drugs respectively for validation and optimization the selectivity
      and suitability of the comprehensive two-dimensional chromatographic system. Five
      compounds, sophocarpine, matrine, oxymatrine, oxysophocarpine, and xanthohumol
      were found to have significant retention behaviors on the PC-3 cell membrane
      chromatography and were unambiguously identified by time-of-flight mass
      spectrometry. Cell proliferation and apoptosis assays confirmed that all five
      compounds had anti-prostate cancer effects. Matrine and xanthohumol had good
      inhibitory effects, with half maximal inhibitory concentration values of 0.893
      and 0.137 mg/mL, respectively. Our comprehensive two-dimensional PC-3 prostate
      cancer cell membrane chromatographic system promotes the efficient recognition
      and rapid analysis of drug candidates, and it will be practical for the discovery
      of prostate cancer drugs from complex traditional Chinese medicines.

PMID- 28432775
TI  - Application for lower facial fat reduction and tightening by static type
      monopolar 1-MHz radio frequency for body contouring.
AB  - INTRODUCTION: Liposuction and mesotherapy are popular treatments for fat
      reduction of lower face, but because these treatments are invasive, a novel non
      invasive treatment with similar or better efficacy has been sought. There are
      various devices such as CoolSculpt, laser, RF, and HIFU that are used as non
      invasive treatments for fat reduction and body contouring, but these applications
      have not been applied to facial fat reduction. In this study, we selected
      Monopolar 1-MHz RF for body contouring to be applied for fat reduction and
      tightening of the lower face. MATERIAL AND METHODS: From March through August of
      2016, we treated fourteen Asian women (average age: 44.6 years old) for fat
      reduction and tightening of the lower face using 1-MHz Monopolar RF (truSculptTM,
      Cutera, Inc., Brisbane, CA). We performed the treatment primarily in the
      nasolabial fold and buccal area weekly for five consecutive weeks, and evaluated
      the effects for fat reduction and tightening before each treatment and for 2
      months after the treatment using handy VECTRA 3D(r) (Canfield Scientific, Inc.)
      for imaging. Three-dimensional (3D) volumetric assessments were performed at pre-
      and post-two-months after treatment. Patients rated their satisfaction for
      tightening using a 5-points scale. RESULTS: During the study, more than ninety
      percent of patients showed volumetric change by fat reduction at the treated
      area, with an average of 2.7 ml. Sixty percent of patients were either
      "satisfied" or "very satisfied" with the tightening effects. The treatments were
      accompanied only by very mild heat pain. Efficacy was maintained for 2 months
      after the treatments, and three patients showed a higher fat reduction effect at
      2 months after the final treatment compared with the final treatment. A mild
      redness was observed just for few hours after the treatment, but complications
      such as, swelling, induration, burn, sensory disturbance or facial paralysis,
      were not observed. CONCLUSION: In this study, we found that Monopolar 1-MHz RF
      applied with a stationary applicator was effective especially for lower face fat
      reduction and with a tightening effect in facial contouring. A highly efficacious
      treatment with satisfactory comfort and safety can be achieved with no downtime,
      and the device has the potential for becoming one of the standard non-invasive
      treatments for fat reduction of facial contouring. Lasers Surg. Med.49:750-755,
      2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28432776
TI  - Exploring Non-obvious Hydrophobic Binding Pockets on Protein Surfaces: Increasing
      Affinities in Peptide-Protein Interactions.
AB  - A 42-residue polypeptide conjugated to a small-molecule organic ligand capable of
      targeting the phosphorylated side chain of Ser15 was shown to bind glycogen
      phosphorylase a (GPa) with a KD value of 280 nm. The replacement of hydrophobic
      amino acids by Ala reduced affinities, whereas the incorporation of l-2
      aminooctanoic acid (Aoc) increased them. Replacing Nle5, Ile9 and Leu12 by Aoc
      reduced the KD value from 280 to 27 nm. "Downsizing" the 42-mer to an undecamer
      gave rise to an affinity for GPa an order of magnitude lower, but the undecamer
      in which Nle5, Ile9 and Leu12 were replaced by Aoc showed a KD value of 550 nm,
      comparable with that of the parent 42-mer. The use of Aoc residues offers a
      convenient route to increased affinity in protein recognition as well as a
      strategy for the "downsizing" of peptides essentially without loss of affinity.
      The results show that hydrophobic binding sites can be found on protein surfaces
      by comparing the affinities of polypeptide conjugates in which Aoc residues
      replace Nle, Ile, Leu or Phe with those of their unmodified counterparts.
      Polypeptide conjugates thus provide valuable opportunities for the optimization
      of peptides and small organic compounds in biotechnology and biomedicine.

PMID- 28432777
TI  - Preparative isoelectric focusing in a cellulose-based separation medium.
AB  - An improved preparative method based on isoelectric focusing of analytes in a
      cellulose-based separation medium is described in this study. Cellulose is
      suspended in an aqueous solution of simple buffers, ethylene glycol, glycerol,
      nonionic surfactant, and colored pI markers. Water partially evaporates during
      focusing run and the separation takes place in an in situ generated layer of
      cellulose, which has a gel-like appearance at the end of analysis. Final
      positions of analytes are indicated by the positions of zones of focused pI
      markers. Fractions, segments of the separation medium with analytes, can be
      simply collected by spatula and analyzed by downstream analytical methods. Good
      focusing ability of the new method and almost quantitative recovery of model
      proteins, cytochrome c and bovine serum albumin, was verified by gel
      electrophoresis and capillary isoelectric focusing of the collected fractions.

PMID- 28432778
TI  - Cross-species studies of cognition relevant to drug discovery: a translational
      approach.
AB  - This review advances the case that bidirectional, cross-species translation of
      findings from experimental animals to and from humans is an important strategy
      for drug discovery. Animal models of mental disorders require appropriate
      behavioural or cognitive outcome variables that can be generalized cross-species.
      One example is the treatment of impulsive behaviour in attention deficit
      hyperactivity disorder (ADHD) with stimulant drugs. Performance on the stop
      signal reaction task as an index of impulsivity is improved both in healthy human
      volunteers and in patients with adult ADHD by stimulant drugs and also by the
      selective noradrenaline reuptake blocker atomoxetine. Functional neuroimaging
      evidence suggests a modulation of circuitry including the inferior prefrontal
      cortex by this drug. Parallel work in rats had shown that atomoxetine improves
      stop signal performance by affecting possibly homologous regions of the rodent
      prefrontal cortex. This parallel effect of atomoxetine in rodents and humans
      could potentially be exploited in other disorders in which impulsivity plays a
      role, such as stimulant abuse and Parkinson's disease. A contrasting relative
      lack of involvement of 5-HT mechanisms in the stop signal reaction time task will
      also be described. Research in humans and experimental animals that demonstrate
      effects of serotoninergic agents such as the selective serotonin (5-HT) reuptake
      inhibitor citalopram on probabilistic learning and reversal (upon which
      atomoxetine has little effect) will also be reviewed, possibly relevant to the
      treatment of clinical depression, Finally, other promising examples of parallel
      studies of behavioural effects of CNS-active drugs in animals and humans will
      also be described. Linked Articles This article is part of a themed section on
      Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the
      other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.

PMID- 28432780
TI  - Single-subject independent component analysis-based intensity normalization in
      non-quantitative multi-modal structural MRI.
AB  - Non-quantitative MRI is prone to intersubject intensity variation rendering
      signal intensity level based analyses limited. Here, we propose a method that
      fuses non-quantitative routine T1-weighted (T1w), T2w, and T2w fluid-saturated
      inversion recovery sequences using independent component analysis and validate it
      on age and sex matched healthy controls. The proposed method leads to consistent
      and independent components with a significantly reduced coefficient-of-variation
      across subjects, suggesting potential to serve as automatic intensity
      normalization and thus to enhance the power of intensity based statistical
      analyses. To exemplify this, we show that voxelwise statistical testing on single
      subject independent components reveals in particular a widespread sex difference
      in white matter, which was previously shown using, for example, diffusion tensor
      imaging but unobservable in the native MRI contrasts. In conclusion, our study
      shows that single-subject independent component analysis can be applied to
      routine sequences, thereby enhancing comparability in-between subjects. Unlike
      quantitative MRI, which requires specific sequences during acquisition, our
      method is applicable to existing MRI data. Hum Brain Mapp, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28432779
TI  - NMDAR-independent hippocampal long-term depression impairment after status
      epilepticus in a lithium-pilocarpine model of temporal lobe epilepsy.
AB  - Temporal lobe epilepsy is usually associated with cognitive decline and memory
      deficits. Despite numerous existing studies on various animal models, the
      mechanisms of these deficits remain largely unclear. A specific form of long-term
      synaptic efficacy changes-long-term depression (LTD)-is thought to play an
      important role in memory formation and learning. However, extremely little is
      known about the possible alteration of LTD induction and dynamics after a status
      epilepticus (SE). In this work, we investigated the acute and delayed effects of
      lithium-pilocarpine-induced SE on NMDAR-dependent and NMDAR-independent
      hippocampal LTD in vitro. We found that SE affected the NMDAR-dependent and NMDAR
      independent forms of LTD in different manners. The NMDAR-dependent form of LTD
      was almost intact 3 days after SE, but it switched from a predominantly
      presynaptic to a more postsynaptic locus of expression. In contrast, the NMDAR
      independent LTD in the hippocampal Schaffer collaterals-CA1 synapses was fully
      abolished 3 days after SE. Our results emphasize the role of non-NMDA-dependent
      synaptic plasticity changes in the processes of epileptogenesis and the potential
      for therapy development.

PMID- 28432782
TI  - The good lies: Altruistic goals modulate processing of deception in the anterior
      insula.
AB  - When it comes to lies, the beneficiaries of one's dishonesty play an important
      role in the decision-making process. Altruistic lies that are made with the
      intention of benefiting others are a specific type of lies and very common in
      real life. While it has been shown that altruistic goals influence (dis)honest
      behaviors, the neural substrates of this effect is still unknown. To reveal how
      the brain integrates altruistic goals into (dis)honest decisions, this study used
      functional magnetic resonance imaging to examine the neural activity of
      participants in a real incentivized context while they were making (dis)honest
      decisions. We manipulated the beneficiaries of individuals' decisions (self vs. a
      charity) and whether the choices of higher payoffs involved deception or not.
      While finding that participants lied more often to benefit charities than for
      themselves, we observed that the altruistic goal of benefiting a charity,
      compared with the self-serving goal, reduced the activity in the anterior insula
      (AI) when lying to achieve higher payoffs. Furthermore, the degree of altruistic
      goal-induced reduction of AI activity was positively correlated with the degree
      of altruistic goal-induced reduction of honesty concerns. These results suggest
      that the AI serves as a neural hub in modulating the effect of altruistic goals
      on deception, which shed light on the underlying neural mechanism of altruistic
      lies. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28432781
TI  - Cognitive functioning and emotion processing in breast cancer survivors and
      controls: An ERP pilot study.
AB  - Diagnosis and treatment of breast cancer is a very emotionally aversive and
      stressful life event, which can lead to impaired cognitive functioning and mental
      health. Breast cancer survivors responding with repressive emotion regulation
      strategies often show less adaptive coping and adverse outcomes. We investigated
      cognitive functioning and neural correlates of emotion processing using ERPs.
      Self-report measures of depression, anxiety, and fatigue, as well as hair
      cortisol as an index of chronic stress, were assessed. Twenty breast cancer
      survivors (BCS) and 31 carefully matched healthy controls participated in the
      study. After neuropsychological testing and subjective assessments, participants
      viewed 30 neutral, 30 unpleasant, and 30 pleasant pictures, and ERPs were
      recorded. Recognition memory was tested 1 week later. BCS reported stronger
      complaints about cognitive impairments and more symptoms of depression, anxiety,
      and fatigue. Moreover, they showed elevated hair cortisol levels. Except for
      verbal memory, cognitive functioning was predominantly in the normative range.
      Recognition memory performance was decreased in cancer survivors, especially for
      emotional contents. In ERPs, survivors showed smaller late positive potential
      amplitudes for unpleasant pictures relative to controls in a later time window,
      which may indicate less elaborative processing of this material. Taken together,
      we found cognitive impairments in BCS in verbal memory, impaired emotional
      picture memory accuracy, and reduced neural activity when breast cancer survivors
      were confronted with unpleasant materials. Further studies and larger sample
      sizes, however, are needed to evaluate the relationship between altered emotion
      processing and reduced memory in BCS in order to develop new treatment
      strategies.

PMID- 28432783
TI  - Gene structure and expression characteristic of a novel odorant receptor gene
      cluster in the parasitoid wasp Microplitis mediator (Hymenoptera: Braconidae).
AB  - Odorant receptors (ORs) expressed in the antennae of parasitoid wasps are
      responsible for detection of various lipophilic airborne molecules. In the
      present study, 107 novel OR genes were identified from Microplitis mediator
      antennal transcriptome data. Phylogenetic analysis of the set of OR genes from M.
      mediator and Microplitis demolitor revealed that M. mediator OR (MmedOR) genes
      can be classified into different subfamilies, and the majority of MmedORs in each
      subfamily shared high sequence identities and clear orthologous relationships to
      M. demolitor ORs. Within a subfamily, six MmedOR genes, MmedOR98, 124, 125, 126,
      131 and 155, shared a similar gene structure and were tightly linked in the
      genome. To evaluate whether the clustered MmedOR genes share common regulatory
      features, the transcription profile and expression characteristics of the six
      closely related OR genes were investigated in M. mediator. Rapid amplification of
      cDNA ends-PCR experiments revealed that the OR genes within the cluster were
      transcribed as single mRNAs, and a bicistronic mRNA for two adjacent genes
      (MmedOR124 and MmedOR98) was also detected in female antennae by reverse
      transcription PCR. In situ hybridization experiments indicated that each OR gene
      within the cluster was expressed in a different number of cells. Moreover, there
      was no co-expression of the two highly related OR genes, MmedOR124 and MmedOR98,
      which appeared to be individually expressed in a distinct population of neurons.
      Overall, there were distinct expression profiles of closely related MmedOR genes
      from the same cluster in M. mediator. These data provide a basic understanding of
      the olfactory coding in parasitoid wasps.

PMID- 28432784
TI  - Contributions of imprecision in PET-MRI rigid registration to imprecision in
      amyloid PET SUVR measurements.
AB  - Quantitative measurement of beta-amyloid from amyloid PET scans typically relies
      on localizing target and reference regions by image registration to MRI. In this
      work, we present a series of simulations where 50 small random perturbations of
      starting location and orientation were applied to each subject's PET scan, and
      rigid registration using spm_coreg was performed between each perturbed PET scan
      and its corresponding MRI. We then measured variation in the output PET-MRI
      registrations and how this variation affected the resulting SUVR measurements. We
      performed these experiments using scans of 1196 participants, half using 18F
      florbetapir and half using 11C PiB. From these experiments, we measured the
      magnitude of the imprecision in the rigid registration steps used to localize
      measurement regions, and how this contributes to the overall imprecision in SUVR
      measurements. Unexpectedly, we found for both tracers that the imprecision in
      these measurements depends on the degree of amyloid tracer uptake, and thus also
      indirectly on Alzheimer's disease clinical status. We then examined common
      choices of reference regions, and we show that SUVR measurements using
      supratentorial white matter references are relatively resistant to this source of
      error. We also show that the use of partial volume correction further magnifies
      the effects of registration imprecision on SUVR measurements. Together, these
      results suggest that this rigid registration step is an attractive target for
      future work in improving measurement techniques. Hum Brain Mapp, 2017. (c) 2017
      The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

PMID- 28432785
TI  - Phosphorylation of iRhom2 at the plasma membrane controls mammalian TACE
      dependent inflammatory and growth factor signalling.
AB  - Proteolytic cleavage and release from the cell surface of membrane-tethered
      ligands is an important mechanism of regulating intercellular signalling. TACE is
      a major shedding protease, responsible for the liberation of the inflammatory
      cytokine TNFalpha and ligands of the epidermal growth factor receptor. iRhoms,
      catalytically inactive members of the rhomboid-like superfamily, have been shown
      to control the ER-to-Golgi transport and maturation of TACE. Here, we reveal that
      iRhom2 remains associated with TACE throughout the secretory pathway, and is
      stabilised at the cell surface by this interaction. At the plasma membrane,
      ERK1/2-mediated phosphorylation and 14-3-3 protein binding of the cytoplasmic
      amino-terminus of iRhom2 alter its interaction with mature TACE, thereby
      licensing its proteolytic activity. We show that this molecular mechanism is
      responsible for triggering inflammatory responses in primary mouse macrophages.
      Overall, iRhom2 binds to TACE throughout its lifecycle, implying that iRhom2 is a
      primary regulator of stimulated cytokine and growth factor signalling.

PMID- 28432786
TI  - The comprehensive connectome of a neural substrate for 'ON' motion detection in
      Drosophila.
AB  - Analysing computations in neural circuits often uses simplified models because
      the actual neuronal implementation is not known. For example, a problem in
      vision, how the eye detects image motion, has long been analysed using
      Hassenstein-Reichardt (HR) detector or Barlow-Levick (BL) models. These both
      simulate motion detection well, but the exact neuronal circuits undertaking these
      tasks remain elusive. We reconstructed a comprehensive connectome of the circuits
      of Drosophila's motion-sensing T4 cells using a novel EM technique. We uncover
      complex T4 inputs and reveal that putative excitatory inputs cluster at T4's
      dendrite shafts, while inhibitory inputs localize to the bases. Consistent with
      our previous study, we reveal that Mi1 and Tm3 cells provide most synaptic
      contacts onto T4. We are, however, unable to reproduce the spatial offset between
      these cells reported previously. Our comprehensive connectome reveals complex
      circuits that include candidate anatomical substrates for both HR and BL types of
      motion detectors.

PMID- 28432787
TI  - Presynaptic morphology and vesicular composition determine vesicle dynamics in
      mouse central synapses.
AB  - Transport of synaptic vesicles (SVs) in nerve terminals is thought to play
      essential roles in maintenance of neurotransmission. To identify factors
      modulating SV movements, we performed real-time imaging analysis of fluorescently
      labeled SVs in giant calyceal and conventional hippocampal terminals. Compared
      with small hippocampal terminals, SV movements in giant calyceal terminals were
      faster, longer and kinetically more heterogeneous. Morphological maturation of
      giant calyceal terminals was associated with an overall reduction in SV mobility
      and displacement heterogeneity. At the molecular level, SVs over-expressing
      vesicular glutamate transporter 1 (VGLUT1) showed higher mobility than VGLUT2
      expressing SVs. Pharmacological disruption of the presynaptic microtubule network
      preferentially reduced long directional movements of SVs between release sites.
      Functionally, synaptic stimulation appeared to recruit SVs to active zones
      without significantly altering their mobility. Hence, the morphological features
      of nerve terminals and the molecular signature of vesicles are key elements
      determining vesicular dynamics and movements in central synapses.

PMID- 28432788
TI  - Structure of Fam20A reveals a pseudokinase featuring a unique disulfide pattern
      and inverted ATP-binding.
AB  - Mutations in FAM20A cause tooth enamel defects known as Amelogenesis Imperfecta
      (AI) and renal calcification. We previously showed that Fam20A is a secretory
      pathway pseudokinase and allosterically activates the physiological casein kinase
      Fam20C to phosphorylate secreted proteins important for biomineralization (Cui et
      al., 2015). Here we report the nucleotide-free and ATP-bound structures of
      Fam20A. Fam20A exhibits a distinct disulfide bond pattern mediated by a unique
      insertion region. Loss of this insertion due to abnormal mRNA splicing interferes
      with the structure and function of Fam20A, resulting in AI. Fam20A binds ATP in
      the absence of divalent cations, and strikingly, ATP is bound in an inverted
      orientation compared to other kinases. Fam20A forms a dimer in the crystal, and
      residues in the dimer interface are critical for Fam20C activation. Together,
      these results provide structural insights into the function of Fam20A and shed
      light on the mechanism by which Fam20A mutations cause disease.

PMID- 28432791
TI  - Immediate versus delayed postpartum insertion of contraceptive implant for
      contraception.
AB  - BACKGROUND: The spacing of pregnancies has a positive impact on maternal and
      newborn health. The progestin contraceptive implant, which is a long-acting,
      reversible method of contraception, has a well-established low failure rate that
      is compatible with tubal sterilization. The standard provision of contraceptive
      methods on the first postpartum visit may put some women at risk of unintended
      pregnancy, either due to loss to follow-up or having sexual intercourse prior to
      receiving contraception. Therefore, the immediate administration of contraception
      prior to discharge from the hospital that has high efficacy may improve
      contraceptive prevalence and prevent unintended pregnancy. OBJECTIVES: To compare
      the initiation rate, effectiveness, and side effects of immediate versus delayed
      postpartum insertion of implant for contraception. SEARCH METHODS: We searched
      for eligible studies up to 28 October 2016 in the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, Embase, and POPLINE. We examined review
      articles and contacted investigators. We also checked registers of ongoing
      clinical trials, citation lists of included studies, key textbooks, grey
      literature, and previous systematic reviews for potentially relevant studies.
      SELECTION CRITERIA: We sought randomised controlled trials (RCTs) that compared
      immediate postpartum versus delayed insertion of contraceptive implant for
      contraception. DATA COLLECTION AND ANALYSIS: Two review authors (JS, YW)
      independently screened titles and abstracts of the search results, and assessed
      the full-text articles of potentially relevant studies for inclusion. They
      extracted data from the included studies, assessed risk of bias, compared
      results, and resolved disagreements by consulting a third review author (PL or
      SK). We contacted investigators for additional data, where possible. We computed
      the Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI) for binary
      outcomes and the mean difference (MD) with 95% CI for continuous variables. MAIN
      RESULTS: Three studies that included 410 participants met the inclusion criteria
      of the review. We did not identify any ongoing trials. Two included studies were
      at low risk of selection, attrition, and reporting biases, but were at high risk
      of performance and detection biases due to the inability to blind participants to
      the intervention. One included study was at high risk of attrition bias. The
      overall quality of the evidence for each comparison ranged from very low to
      moderate; the main limitations were risk of bias and imprecision.Initiation rate
      of contraceptive implants at the first postpartum check-up visit was
      significantly higher in the immediate insertion group than in the delayed
      insertion group (RR 1.41, 95% CI 1.28 to 1.55; three studies, 410 participants;
      moderate quality evidence).There appeared to be little or no difference between
      the groups in the continuation rate of contraceptive implant used at six months
      after insertion (RR 1.02, 95% CI 0.93 to 1.11; two studies, 125 participants; low
      quality evidence) or at 12 months after insertion (RR 1.04; 95% CI 0.81 to 1.34;
      one study, 64 participants;very low quality evidence)Women who received an
      immediate postpartum contraceptive implant insertion had a higher mean number of
      days of abnormal vaginal bleeding within six weeks postpartum (MD 5.80 days, 95%
      CI 3.79 to 7.81; one study, 215 participants; low quality evidence) and a higher
      rate of other side effects in the first six weeks after birth (RR 2.06, 95% CI
      1.38 to 3.06; one study, 215 participants; low quality evidence) than those who
      received a delayed postpartum insertion. There appeared to be little or no
      difference between the groups in heavy, irregular vaginal bleeding or associated
      severe cramping within 12 months (RR 1.01, 95% CI 0.72 to 1.44, one study, 64
      participants;very low quality evidence).It was unclear whether there was any
      difference between the groups in scores for participant satisfaction on a 0-10
      scale (MD -0.40, 95% CI -1.26 to 0.46, low quality evidence), or in rates of
      unintended pregnancy (RR 1.82, 95% CI 0.38 to 8.71, 1 RCT, 64 women, very low
      quality evidence) at 12 months, or in rate of breastfeeding rate at six months
      (RR 2.01, 95% CI 0.72 ro 5.63, 1 RCT, 64 women, very low quality evidence) rate
      did not differ significantly between the groups. AUTHORS' CONCLUSIONS: Evidence
      from this review indicates that the rate of initiation of contraceptive implant
      at the first postpartum check-up visit was higher with immediate postpartum
      insertion than with delayed insertion. There appeared to be little or no
      difference between the groups in the continuation rate of contraceptive implant
      use at 6 months. It was unclear whether there was any difference between the
      groups in continuation of contraceptive use at 12 months or in the unintended
      pregnancy rate at 12 months.

PMID- 28432790
TI  - Single-molecule visualization of fast polymerase turnover in the bacterial
      replisome.
AB  - The Escherichia coli DNA replication machinery has been used as a road map to
      uncover design rules that enable DNA duplication with high efficiency and
      fidelity. Although the enzymatic activities of the replicative DNA Pol III are
      well understood, its dynamics within the replisome are not. Here, we test the
      accepted view that the Pol III holoenzyme remains stably associated within the
      replisome. We use in vitro single-molecule assays with fluorescently labeled
      polymerases to demonstrate that the Pol III* complex (holoenzyme lacking the
      beta2 sliding clamp), is rapidly exchanged during processive DNA replication.
      Nevertheless, the replisome is highly resistant to dilution in the absence of Pol
      III* in solution. We further show similar exchange in live cells containing
      labeled clamp loader and polymerase. These observations suggest a concentration
      dependent exchange mechanism providing a balance between stability and
      plasticity, facilitating replacement of replisomal components dependent on their
      availability in the environment.

PMID- 28432789
TI  - Probing protein flexibility reveals a mechanism for selective promiscuity.
AB  - Many eukaryotic regulatory proteins adopt distinct bound and unbound
      conformations, and use this structural flexibility to bind specifically to
      multiple partners. However, we lack an understanding of how an interface can
      select some ligands, but not others. Here, we present a molecular dynamics
      approach to identify and quantitatively evaluate the interactions responsible for
      this selective promiscuity. We apply this approach to the anticancer target PD-1
      and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a
      hard-to-drug hydrophilic interface, conserved specific triggers encoded in the
      cognate ligands activate a promiscuous binding pathway that reveals a flexible
      hydrophobic binding cavity. Specificity is then established by additional
      contacts that stabilize the PD-1 cavity into distinct bound-like modes.
      Collectively, our studies provide insight into the structural basis and evolution
      of multiple binding partners, and also suggest a biophysical approach to exploit
      innate binding pathways to drug seemingly undruggable targets.

PMID- 28432792
TI  - Monte Carlo study of the chamber-phantom air gap effect in a magnetic field.
AB  - PURPOSE: The aim of this study was to examine the effect of submillimeter air
      gaps that may exist between an ionization chamber and solid phantoms when
      measurements are performed in a magnetic field. METHODS: Geant4 Monte Carlo
      simulations were performed using a model of a PTW 30013 Farmer chamber in a water
      phantom. Symmetrical and asymmetrical air gaps of various thicknesses were
      modeled surrounding the chamber, and the dose to the air cavity of the chamber
      was scored in each case. Magnetic fields were modeled parallel to the long axis
      of the chamber with strengths of 0, 0.35 T, 1.0 T, and 1.5 T. To examine the
      phenomenon in more detail, the gyroradii of the electrons responsible for the
      energy deposited in the chamber were scored as they entered the chamber and the
      total energy deposited was split into three components: energy originating from
      inside the chamber, in the immediate vacinity of the chamber, or outside the
      chamber. RESULTS: Differences in the chamber dose of 1.6% were observed for
      asymmetric air gaps just 0.2 mm thick. No effect greater than 0.5% was observed
      for the symmetrical air gaps investigated in this work (1.4 mm thick or less) for
      this chamber/magnetic field configuration. The mean gyroradius of contributing
      electrons as they first enter the chamber was 4 mm. The presence of the air gap
      reduced the energy contributions from electrons released in the immediate
      vicinity of the chamber, and this loss was not completely compensated for when a
      magnetic field was present. CONCLUSIONS: The gyroradius of most electrons was too
      large to be responsible for the air gap effect via the electron return effect;
      instead, the effect is attributed to the loss of energy contributions from
      electrons originating inside the air gap volume, which is not completely
      compensated for by more distant electrons owing to their reduced range in the
      magnetic field. When the chamber is parallel with the magnetic field, symmetric
      air gaps have a smaller effect (< 0.5%) compared to asymmetric air-gaps (up to
      1.6%) on the chamber response.

PMID- 28432793
TI  - Single and dual cyclodextrins systems for the enantiomeric and diastereoisomeric
      separations of structurally related dihydropyridone analogues.
AB  - CD capillary electrophoresis methods were developed for complete enantiomeric and
      diastereoisomeric separations of a series of ten dihydropyridone analogues, of
      which eight were neutral, one was anionic, and one was cationic. Ten different
      systems comprising one or two CDs were found to successfully separate the isomers
      thanks to a screening approach. Among the tested CDs, highly sulfated-gamma-CD
      (HS-gamma-CD), either in a single or in a dual system, in a phosphate buffer
      using capillaries dynamically coated with polyethylene oxide, and SBE-beta-CD,
      either in a single or in a dual system, in a borate buffer using uncoated
      capillaries, were the most selective selectors. The effects of different
      parameters such as the nature and concentration of the CDs, nature and
      concentration of the buffer, and voltage were examined. The precision and LODs
      and limits of quantification were evaluated for the optimized methods.

PMID- 28432794
TI  - Posttraumatic stress and anxiety in patients with an implantable cardioverter
      defibrillator: Trajectories and vulnerability factors.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) therapy is the first
      line treatment for the primary and secondary prevention of sudden cardiac death.
      Despite the unequivocal medical benefits, living with an ICD may affect patients'
      psychological functioning and general well-being. We examined the trajectories of
      symptoms of posttraumatic stress disorder (PTSD) and anxiety in patients with an
      ICD and the vulnerability factors associated with an increased risk of symptoms
      of PTSD and anxiety. METHODS: A total of 249 patients were included as part of
      the WEB-based distress program for implantable CARdioverter dEfibrillator
      patients (WEBCARE) study. Data were analyzed using Latent class analyses, with
      trajectories of PTSD symptomatology and anxiety examined between baseline and 12
      months follow-up. RESULTS: The mean age of the sample was 58.9 +/- 9.8, with the
      majority being male (82%). Latent Class analyses (LatentGOLD) revealed four
      classes with respect to PTSD symptomatology, and three classes of patients with
      respect to anxiety. Younger age, increased depression score at baseline, and Type
      D personality were all associated with increased vulnerability for posttraumatic
      stress and anxiety symptoms. CONCLUSION: Comparable trajectories were found for
      symptoms of PTSD and anxiety over time. Patients with a younger age, increased
      depression score at baseline, and Type D personality were especially prone to
      experience PTSD and anxiety symptomatology at 12 months follow-up. Due to the
      negative association between PTSD, anxiety, and health outcomes, it is paramount
      to timely identify the subset of patients who are vulnerable to experience these
      symptoms and provide them with personalized support.

PMID- 28432795
TI  - Validation of Sun Exposure Reported Annually Against Interim Self-report and
      Daily Sun Diaries.
AB  - Data on personal sun exposure over a period exceeding the immediate past days or
      weeks are typically self-reported in brief questionnaire items. The validity of
      such self-reporting of longer term personal sun exposure, for example over a
      year, including detail on variation across seasons, has not previously been
      investigated. In a volunteer sample (n = 331) of Australian adults aged 18 years
      and over, we assessed the 12-month reliability of sun exposure reported
      separately for each season, and its accuracy compared to a daily sun diary in the
      same season. Seasonal time outdoors displayed fair-to-good reliability between
      baseline and end of study (12 months), with responses showing higher agreement at
      lower levels of time outdoors. There was good agreement for ranking of
      individuals' time outdoors with the daily sun diary data, although the actual
      diary time outdoors was typically considerably lower than the self-reported
      questionnaire data. Place of residence, education, being a smoker, day of the
      week (i.e. working day vs nonworking day) and working mainly outdoors were
      significant predictors of agreement. While participants overestimated their
      actual time outdoors, the self-report questionnaire provided a valid ranking of
      long-term sun exposure against others in the study that was reliable over time.

PMID- 28432796
TI  - An acetone-based phantom for quantitative diffusion MRI.
AB  - PURPOSE: To propose and evaluate an acetone-D2 O phantom that has an extended
      range of apparent diffusion coefficient (ADC) for quantitative diffusion magnetic
      resonance imaging (MRI), as well as to compare its properties to previously
      described water-based phantoms. MATERIALS AND METHODS: The proposed acetone-D2 O,
      and previously described sucrose water solution and polyvinylpyrrolidone (PVP)
      water solution phantoms, were constructed in a number of concentrations between
      0% and 50%. At 1.5T field strength, diffusion-weighted MR spectroscopy (DW-MRS),
      based on a point-resolved spectroscopy (PRESS) acquisition, nondiffusion-weighted
      stimulated echo acquisition mode (STEAM)-MRS, and diffusion-weighted echo-planar
      imaging (DW-EPI) were used to evaluate each phantom. The MR spectra, diffusion
      weighted signal decay pattern, tunability of ADC, and ADC range of each phantom
      were all evaluated. RESULTS: When placed in an ice-water bath, all phantoms
      provided desirable signal properties, including single-peak signal with Gaussian
      diffusion and tunable ADC. At 0 degrees C, however, water-based phantoms had ADC
      limited to less than 1.1.10-3 mm2 .s-1 (0.2-1.1.10-3 mm2 .s-1 ), while the
      proposed acetone-based phantom had ADC values spanning a wider range (0.6-3.5.10
      3 mm2 .s-1 ). CONCLUSION: The proposed acetone-D2 O phantom provided desirable
      signal properties over a wide range of ADCs with temperature controlled using an
      ice-water bath. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson.
      Imaging 2017;46:1683-1692.

PMID- 28432797
TI  - Effects of Levothyroxine Administration and Withdrawal on the Hypothalamic
      Pituitary-Thyroid Axis in Euthyroid Dogs.
AB  - BACKGROUND: Chronic supplementation can suppress the hypothalamic-pituitary
      thyroid axis (HPTA) and make it difficult to assess thyroid function after
      withdrawal of levothyroxine. OBJECTIVES: To determine whether the HPTA is
      suppressed after levothyroxine administration in euthyroid dogs and the time
      required for resolution of any suppression. ANIMALS: Twenty-eight healthy
      euthyroid dogs. METHODS: A prospective, randomized study administering
      levothyroxine to euthyroid dogs for 8 weeks (group 1) or 16 weeks (group 2).
      Serum concentrations of total thyroxine (T4 ), free thyroxine (fT4 ) by
      equilibrium dialysis, thyroid stimulating hormone; thyrotropin (TSH), and 3,5,3'
      triiodothyronine (T3 ) were measured every 4 weeks during supplementation and for
      16 weeks after levothyroxine was discontinued. RESULTS: Mean serum concentrations
      of T4 and fT4 were significantly higher (P < .0001) and TSH was lower (P < .0001)
      in all dogs during levothyroxine administration compared to baseline. Mean serum
      concentrations of T4 , fT4, and TSH in both groups, beginning 1 week after
      levothyroxine was discontinued, were significantly different (P < .01) compared
      to values during levothyroxine administration but not compared to baseline values
      (P > .3). CONCLUSIONS AND CLINICAL IMPORTANCE: Assessing thyroid function tests 1
      week after cessation of levothyroxine at 26 MUg/kg once a day for up to 16 weeks
      will provide an accurate assessment of thyroid function in healthy euthyroid
      dogs.

PMID- 28432798
TI  - Therapeutic drug monitoring of mitotane: Analytical assay and patient follow-up.
AB  - Adrenocortical carcinoma (ACC) is an aggressive malignancy of the adrenal gland.
      Mitotane (o,p'-DDD) is the most effective chemotherapy for ACC. According to the
      literature, mitotane plasma trough concentrations within 14-20 mg L-1 are
      correlated with a higher response rate with acceptable toxicity. Therapeutic drug
      monitoring (TDM) of mitotane is therefore recommended. The aim of this study was
      to propose a robust and simple method for mitotane quantification in plasma. The
      validation procedures were based on international guidelines. Sample preparation
      consisted of a single protein precipitation with methanol using 100 MUL of
      plasma. The supernatant was submitted to liquid chromatography coupled with ultra
      violet detection at 230 nm. Mitotane retention time was 7.1 min. The limit of
      detection was 0.1 mg L-1 and the limit of quantification was 0.78 mg L-1 . The
      assay demonstrated a linear range of 0.78-25 mg L-1 with correlation coefficients
      (r2 ) at 0.999. Inter- and intra-assay precision was <4.85%. Evaluation of
      accuracy showed a deviation <13.69% from target concentration at each quality
      control level. This method proved easy and rapid to perform mitotane TDM and
      required a small volume of sample. It was successfully applied to routine TDM in
      our laboratory.

PMID- 28432799
TI  - The Transformation of Hybrid Silica Nanoparticles from Solid to Hollow or Yolk
      Shell Nanostructures.
AB  - Here, a facile self-templating approach is presented for synthesis of hollow and
      yolk-shell mesoporous silica nanoparticles (HMSNs and YMSNs) through a selective
      etching of hybrid silica nanoparticles. The hybrid silica nanoparticles are from
      the co-condensation of tetraethylorthosilicate (TEOS) and N-[3
      (trimethoxysilyl)propyl]ethylenediamine (TSD) by a simple one-step process. Two
      kinds of products including HMSNs and YMSNs can be easily prepared only by tuning
      the TSD amounts in the precursor. Significantly, the transformation of hollow
      structure does not use any sacrificial template and surface-protective agent. The
      etching mechanism and formation process are systematically investigated by SEM,
      TEM, TG, CHN elemental analysis and Si MAS NMR spectroscopy. The results reveal
      that the selective etching is mainly attributed to the discrepancy in density
      between the outer layer and inner area of hybrid silica, where its inner section
      is more readily dissolved while the outer shell is robust in hydrofluoric acid
      (HF) aqueous solution. Specifically, the new understanding is further extended to
      precisely prepare multi-shelled hollow/yolk-shell silica nanoparticles.

PMID- 28432800
TI  - Effect of N-methyl deuteration on pharmacokinetics and pharmacodynamics of
      enzalutamide.
AB  - Enzalutamide, a second-generation antiandrogen, has been developed for the
      treatment of castration-resistance prostate cancer. We synthesized the deuterated
      analogues 6 and found that it showed higher drug exposure and thus stronger
      antitumor potency in preclinical settings. Compound 6 is being developed
      clinically for the potential to be differentiated from enzalutamide through
      reduced dosages and a higher safety margin.

PMID- 28432801
TI  - Weight loss in obese girls with polycystic ovarian syndrome is associated with a
      decrease in Anti-Muellerian Hormone concentrations.
AB  - OBJECTIVE: The Anti-Muellerian Hormone (AMH) has been reported as surrogate
      marker of antral follicles, which are the origins of hyperandrogenism in
      polycystic ovarian syndrome (PCOS). Therefore, AMH may be useful for the
      diagnosis of PCOS. The objective was to study the longitudinal changes in AMH
      concentrations in girls with and without PCOS. DESIGN: This is a longitudinal
      study of obese girls participating in a 1-year lifestyle intervention. PATIENTS:
      Forty obese girls aged 13-16 years (50% with PCOS) were included in the study.
      Girls with and without PCOS were matched to age, BMI and change in weight status.
      MEASUREMENTS: AMH, gonadotropins, androstenedione, testosterone, oestradiol and
      sex hormone-binding globulin (SHBG) were determined. RESULTS: Obese girls with
      PCOS demonstrated significantly (P<.001) higher AMH concentrations (5.8+/-3.1
      ng/mL) compared to obese girls without PCOS (2.4+/-1.4 ng/mL). None of the girls
      without PCOS had AMH concentrations >=6 ng/mL and none of the PCOS girls showed
      AMH concentrations <=3 ng/mL. Weight loss in girls with PCOS was associated with
      a significant drop in AMH concentrations (-1.4+/-1.8 ng/mL, P=.045). AMH was
      significantly related to testosterone (cross-sectional: b-coefficient 3.7+/-1.7,
      P=.001, longitudinal: b-coefficient 0.54+/-0.47, P=.026) and luteinizing hormone
      (LH) (cross-sectional: b-coefficient 0.05+/-0.04, P=.039, longitudinal: b
      coefficient 0.005+/-0.004, P=.039), but not to any other analysed parameter in
      multiple linear regression analyses adjusted to multiple confounders.
      CONCLUSIONS: AMH was increased in adolescent girls with PCOS and normalized with
      weight loss. AMH was cross-sectionally and longitudinally related to
      hyperandrogenism.

PMID- 28432802
TI  - Subsequent malignancies after allogeneic hematopoietic stem cell transplantation.
AB  - We evaluated 979 patients for the development of post-transplant
      lymphoproliferative disease (PTLD) and solid malignancies after allogeneic
      hematopoietic stem cell transplantations (allo-HSCT) as a late complication. We
      found 15 (1.5%) subsequent malignancies; three of these malignancies were PTLD,
      and twelve were solid tumors. The median time from allo-HSCT to the development
      of PTLD was 9 (3-20) months and that from allo-HSCT to the development of solid
      tumors was 93 (6-316) months. The cumulative incidence of evolving subsequent
      malignancy in patients was 1.3% (+/-0.5 SE) at 5 years and 3.9% (+/-1.2 SE) at 10
      years. The cumulative incidence of developing subsequent malignancy in patients
      with benign hematological diseases as the transplant indication was 7.4%+/-4.2 SE
      at 5 years. More subsequent malignancy developed in patients having >=1 year
      chronic graft-vs-host disease (GVHD; 3.7% in >=1 year chronic GVHD and 0.7% in <1
      year chronic GVHD patient groups, P=.002). Subsequent epithelial tumor risk was
      higher in >=1 year chronic GVHD patients than <1 year (3.7% vs 0.1%, P<.001). In
      multivariate analysis, benign hematological diseases as transplant indication
      (RR: 5.6, CI 95%: 1.4-22.3, P=.015) and >=1 year chronic GVHD (RR: 7.1, 95% CI:
      2.3-22.5, P=.001) were associated with the development of subsequent malignancy.

PMID- 28432803
TI  - Sequencing and functional validation of the JGI Brachypodium distachyon T-DNA
      collection.
AB  - Due to a large and growing collection of genomic and experimental resources,
      Brachypodium distachyon has emerged as a powerful experimental model for the
      grasses. To add to these resources we sequenced 21 165 T-DNA lines, 15 569 of
      which were produced in this study. This increased the number of unique insertion
      sites in the T-DNA collection by 21 078, bringing the overall total to 26 112.
      Thirty-seven per cent (9754) of these insertion sites are within genes (including
      untranslated regions and introns) and 28% (7217) are within 500 bp of a gene.
      Approximately 31% of the genes in the v.2.1 annotation have been tagged in this
      population. To demonstrate the utility of this collection, we phenotypically
      characterized six T-DNA lines with insertions in genes previously shown in other
      systems to be involved in cellulose biosynthesis, hemicellulose biosynthesis,
      secondary cell wall development, DNA damage repair, wax biosynthesis and
      chloroplast synthesis. In all cases, the phenotypes observed supported previous
      studies, demonstrating the utility of this collection for plant functional
      genomics. The Brachypodium T-DNA collection can be accessed at
      http://jgi.doe.gov/our-science/science-programs/plant
      genomics/brachypodium/brachypodium-t-dna-collection/.

PMID- 28432804
TI  - Premorbid BMI predicts binge-purge symptomatology among individuals with anorexia
      nervosa.
AB  - OBJECTIVE: A finding consistent with the transdiagnostic approach to eating
      disorders is that about half of those with restricting anorexia nervosa (AN)
      eventually undergo a transition to the binge/purge (BP) subtype or to bulimia
      nervosa. Given evidence that individuals with bulimic symptoms exhibit elevated
      weights premorbidly, we tested the hypothesis that among those with AN, highest
      premorbid BMI would predict which individuals with AN would develop AN-BP.
      METHOD: The current study used longitudinal data from a community sample of
      adolescents with AN in Sweden. Premorbid weights were obtained from growth
      charts, and participants were re-assessed at 6, 10, and 18 years after first
      presentation with AN. RESULTS: A greater highest premorbid BMI z score predicted
      a greater likelihood of developing binge/purge symptoms over 18 years.
      DISCUSSION: Among individuals who develop an eating disorder, premorbid BMI may
      be implicated in the type and course of the eating disorder that emerges.

PMID- 28432805
TI  - Pitfalls in electrogram interpretation: Subcutaneous cardioverter defibrillator
      malfunction in Brugada syndrome.
AB  - A patient with Brugada syndrome implanted with subcutaneous implantable
      cardioverter defibrillator (S-ICD) had oversensing episodes treated with S-ICD
      shocks. Comparable artifacts were not evocable with S-ICD pocket manipulation.
      The fluoroscopy excluded S-ICD macroscopic damage. The device extraction revealed
      undamaged pulse generator and connector, but the lead was inappropriately
      tunneled under the sixth rib. Then the S-ICD malfunction was due to lead
      microscopic damage caused by the lead rubbing the rib surface.

PMID- 28432806
TI  - Rapid acceptance testing of modern linac using on-board MV and kV imaging
      systems.
AB  - PURPOSE: The purpose of this study was to develop a novel process for using on
      board MV and kV Electronic Portal Imaging Devices (EPIDs) to perform linac
      acceptance testing (AT) for two reasons: (a) to standardize the assessment of new
      equipment performance, and (b) to reduce the time to clinical use while reducing
      physicist workload. METHODS AND MATERIALS: In this study, Varian TrueBeam linacs
      equipped with amorphous silicon-based EPID (aS1000) were used. The conventional
      set of AT tests and tolerances were used as a baseline guide. A novel methodology
      was developed or adopted from published literature to perform as many tests as
      possible using the MV and kV EPIDs. The developer mode on Varian TrueBeam linacs
      was used to automate the process. In the EPID-based approach, most of mechanical
      tests were conducted by acquiring images through a custom phantom and software
      tools were developed for quantitative analysis to extract different performance
      parameters. The embedded steel-spheres in a custom phantom provided both visual
      and radiographic guidance for beam geometry testing. For photon beams, open field
      EPID images were used to extract inline/crossline profiles to verify the beam
      energy, flatness and symmetry. EPID images through a double wedge phantom were
      used for evaluating electron beam properties via diagonal profile. Testing was
      augmented with a commercial automated application (Machine Performance Check)
      which was used to perform several geometric accuracy tests such as gantry,
      collimator rotations, and couch rotations/translations. RESULTS: The developed
      process demonstrated that the tests, which required customer demonstration, were
      efficiently performed using EPIDs. The AT tests that were performed using EPIDs
      were fully automated using the developer mode on the Varian TrueBeam system,
      while some tests, such as the light field versus radiation field congruence, and
      collision interlock checks required user interaction. CONCLUSIONS: On-board
      imagers are quite suitable for both geometric and dosimetric testing of linac
      system involved in AT. Electronic format of the acquired data lends itself to
      benchmarking, transparency, as well as longitudinal use of AT data. While the
      tests were performed on a specific model of a linear accelerator, the proposed
      approach can be extended to other linacs.

PMID- 28432807
TI  - Incidental Findings in Student Ultrasound Models: Implications for Instructors.
AB  - As ultrasonography continues to become integrated into undergraduate medical
      education, there have been concerns raised about the use of volunteer models and
      the ability to maintain patient privacy during scanning sessions. To date, there
      have been no reports on how instructors should manage situations in which
      incidental findings are made during educational ultrasonography sessions. We
      present three different examples of incidental findings that occurred at our
      institution and the various approaches taken by the instructors. Furthermore, we
      outline an approach that can be utilized by other medical schools to better
      maintain patient confidentiality.

PMID- 28432808
TI  - Mechanism of the vasorelaxant effect induced by trans-4-methyl-beta-nitrostyrene,
      a synthetic nitroderivative, in rat thoracic aorta.
AB  - Mechanisms underlying the vasorelaxant effects of trans-4-methyl-beta
      nitrostyrene (T4MeN) were studied in rat aortic rings. In endothelium-intact
      preparations, T4MeN fully and similarly relaxed contractions induced by
      phenylephrine (PHE) (IC50  = 61.41 [35.40-87.42] MUmol/L) and KCl (IC50  = 83.50
      [56.63-110.50] MUmol/L). The vasorelaxant effect of T4MeN was unchanged by
      endothelium removal, pretreatment with L-NAME, indomethacin, tetraethylammonium,
      ODQ or MDL-12,330A. Under Ca2+ -free conditions, T4MeN significantly reduced with
      a similar potency: (i) phasic contractions induced by PHE, but not by caffeine;
      (ii) contractions due to CaCl2 in aortic preparations stimulated with PHE (in the
      presence of verapamil) or high KCl; (iii) contractions evoked by the restoration
      of external Ca2+ levels after depletion of intracellular Ca2+ stores in the
      presence of thapsigargin. In contrast, T4MeN was more potent at inhibiting
      contractions evoked by the tyrosine phosphatase inhibitor, sodium orthovanadate,
      than those induced by the activator of PKC, phorbol-12,13-dibutyrate. These
      results suggest that T4MeN induces an endothelium- independent vasorelaxation
      that appears to occur intracellularly through the inhibition of contractions that
      are independent of Ca2+ influx from the extracellular milieu but involve
      phosphorylation of tyrosine residues.

PMID- 28432809
TI  - The honeybee as a model insect for developmental genetics.
AB  - Honeybees are an important component of modern agricultural systems, and a
      fascinating and scientifically engrossing insect. Honeybees are not commonly used
      as model systems for understanding development in insects despite their
      importance in agriculture. Honeybee embryogenesis, while being superficially
      similar to Drosophila, is molecularly very different, especially in axis
      formation and sex determination. In later development, much of honeybee biology
      is modified by caste development, an as yet poorly understood, but excellent,
      system to study developmental plasticity. In adult stages, developmental
      plasticity of the ovaries, related to reproductive constraint exhibits another
      aspect of plasticity. Here they review the tools, current knowledge and
      opportunities in honeybee developmental biology, and provide an updated embryonic
      staging scheme to support future studies.

PMID- 28432810
TI  - Cirrhosis is a risk factor for atrial fibrillation: A nationwide, population
      based study.
AB  - BACKGROUND & AIMS: Information is lacking regarding whether cirrhosis is
      associated with atrial fibrillation development. We aimed to investigate the
      incidence and clinical significance of atrial fibrillation in cirrhotic patients.
      METHODS: Cirrhotic patients (n=3596; mean age, 54.7+/-12.3 years; male, 72.5%)
      without previous atrial fibrillation were selected from the Korean National
      Health Insurance Service National Sample Cohort database between 2004 and 2008.
      Age- and sex-matched controls (n=17 980) were randomly sampled in a 5:1 ratio
      from non-cirrhotic individuals. Both cohorts were followed up for incident atrial
      fibrillation and death until 2013. RESULTS: During 9 years of follow-up, atrial
      fibrillation was newly detected in 113 (3.1%) cirrhosis patients and 385 (2.1%)
      controls (incidence: 3.48 and 2.16 per 1000 person-years respectively). Cirrhotic
      patients were at higher risk for atrial fibrillation development compared to
      controls (hazard ratio, 1.46; 95% confidence interval, 1.18-1.80) after
      multivariate adjustment. On subgroup analysis, cirrhosis increased the risk for
      atrial fibrillation, especially in younger (age younger than 65 years) men
      without comorbidities (CHA2 DS2 -VASc score, 0). Cirrhotic patients showed
      increased overall mortality compared to controls (hazard ratio, 4.80; 95%
      confidence interval, 4.47-5.15) as well as increased cardiovascular mortality
      (hazard ratio, 1.37; 95% confidence interval, 1.07-1.75). However, there was no
      significant association between development of atrial fibrillation and increased
      mortality in cirrhosis patients (P=.188 and .260). CONCLUSIONS: Cirrhosis was an
      independent risk factor for atrial fibrillation development, especially in
      younger, otherwise healthy men, stressing the importance of cardiac assessment in
      cirrhotic patients. Meanwhile, atrial fibrillation development in cirrhosis
      patients was not associated with increased mortality.

PMID- 28432811
TI  - Characterization of Host Cell Mutants Significantly Resistant to Cryptosporidium
      parvum Infection.
AB  - Cryptosporidium parvum is a parasitic protist and a causative agent of mild-to
      severe diarrheal diseases in humans and animals. Despite its globally recognized
      importance, knowledge on the mechanism of parasite invasion and molecular
      interactions between host cells and the parasite is limited. Here, we report the
      establishment of 43 mutant cell lines derived from HCT-8 cells by UV-induced
      mutagenesis and the characterization of three mutants with significantly reduced
      susceptibility to cryptosporidial infection. Based on qRT-PCR assay performed at
      18 h postinfection time, the parasite loads could be reduced by ~45%, ~35%, and
      ~20% in mutants A05, B08, and B12, respectively (p < 0.001 in all three mutants
      vs. HCT-8 cells). The mutagenesis mainly affected the attachment of parasite in
      A05 (i.e. ~30% reduction, p < 0.001 vs. HCT-8), and intracellular development in
      B08 and B12. The three cell mutants may serve as valuable reagents to further
      investigate the mechanism of parasite invasion and intracellular development by
      identifying the gene mutations associated with the parasite attachment (A05) and
      intracellular development (B08 and B12).

PMID- 28432812
TI  - Preparation, characterization, and in vivo study of rhein solid lipid
      nanoparticles for oral delivery.
AB  - In this study, rhein-SLNs were successfully produced by hot homogenization
      followed by ultrasonication. Precirol ATO5 in which rhein exhibited higher
      partition coefficient was selected for preparation of SLNs. In the dynamic light
      scattering, the rhein-SLNs showed a smaller size with a mean value of 120.8 +/-
      7.9 nm and with zeta potential of -16.9 +/- 2.3 mV. SLNs exhibited a good
      stability during the period of 2 months. The SLNs indicated faster drug release
      with a burst release within 2 hr and followed by a sustained release with a
      biphasic drug-release pattern. Comparing with the same concentration (free drug),
      the cellular cytotoxicity of rhein-loaded SLNs increased significantly at the
      same incubation condition. In vivo, the AUC0-t of rhein in the form of SLNs was
      significantly increased and was 2.06-fold that of suspensions group. The results
      showed an increased oral absorption and improved the oral bioavailability of
      rhein by the formulation of SLNs.

PMID- 28432813
TI  - Targeting on poly(ADP-ribose) polymerase activity with DNA-damaging hybrid lactam
      steroid alkylators in wild-type and BRCA1-mutated ovarian cancer cells.
AB  - Conjugated lactam-steroid alkylators (LSA) have been shown to exhibit superior
      activity at controlling cancer models and overlap drug resistance to conventional
      chemjournalapy. Hybrid LSA combine two active compounds in a single molecule and
      incorporate modified steroids bearing lactam moiety in one or more steroid rings
      functioning as vectors for cytotoxic agents. We first describe a novel class of
      LSA that generate excellent anticancer activity against UWB1.289 and UWB1.289 +
      BRCA1 human ovarian cancer cell lines. Both UWB1.289 and UWB1.289 + BRCA1 cells
      carry mutations in the tumor suppressor gene TP53 while UWB1.289 cell line
      carries a germline BRCA1 mutation. In vitro, in vivo, and in silico, experimental
      methods were utilized to determine the poly(ADP-ribose) polymerases (PARPs)
      activity and mRNA transcription, DNA damage, cytostatic and cytotoxic effects,
      and virtual molecular interactions, in order to study the molecular mechanisms of
      activity of the tested LSA. LSA produce anticancer activity through dual action
      by combining the direct induction of cellular DNA damage with the inhibition of
      PARP activity and consecutive DNA repair activity. BRCA1-mutated UWB1.289 ovarian
      cancer cells with defective PARP-oriented repair mechanism show significantly
      higher sensitivity to these agents. Combined drug effect on DNA damage and repair
      is a novel approach in cancer therapeutics.

PMID- 28432814
TI  - Do males choose their mates in the lekking moth Achroia grisella? Influence of
      female body mass and male reproductive status on male mate choice.
AB  - Lekking males aggregate to attract females and contribute solely to egg
      fertilization, without any further parental care. Evolutionary theory therefore
      predicts them to be nonchoosy toward their mates, because any lost mating
      opportunities would outweigh the benefits associated with such preferences.
      Nevertheless, due to time costs, the production of energetically costly sexual
      displays, and potential sperm limitation, the mating effort of lekking males is
      often considerable. These factors, combined with the fact that many females of
      varying quality are likely to visit leks, could favor the evolution of male mate
      preferences. Here, we show that males of the lekking lesser wax moth, Achroia
      grisella, were indeed more likely to mate with heavier females in choice
      experiments, even at their virgin mating (i.e., when their reproductive resources
      have not yet been depleted by previous matings). This differential female mating
      success could not be attributed to female behavior as heavy and light females
      showed similar motivation to mate (i.e., latency to approach the males) and time
      to copulate. Males seem to benefit from mating with heavier females, as fecundity
      positively correlated with female mass. This new empirical evidence shows that
      male mate choice may have been underestimated in lekking species.

PMID- 28432815
TI  - Immunoassays for the quantification of ALK and phosphorylated ALK support the
      evaluation of on-target ALK inhibitors in neuroblastoma.
AB  - Targeted inhibition of anaplastic lymphoma kinase (ALK) is a successful approach
      for the treatment of many ALK-aberrant malignancies; however, the presence of
      resistant mutations necessitates both the development of more potent compounds
      and pharmacodynamic methods with which to determine their efficacy. We describe
      immunoassays designed to quantitate phosphorylation of ALK, and their use in
      preclinical models of neuroblastoma, a pediatric malignancy in which gain-of
      function ALK mutations predict a poor overall outcome to conventional treatment.
      Validation of the immunoassays is presented using a panel of neuroblastoma cell
      lines and evidence of on-target ALK inhibition provided by treatment of a
      genetically engineered murine model of neuroblastoma with two clinical ALK
      inhibitors, crizotinib and ceritinib, highlighting the superior efficacy of
      ceritinib.

PMID- 28432816
TI  - Rhodnius prolixus: From classical physiology to modern developmental biology.
AB  - The hemiptera Rhodnius prolixus is a blood-feeding insect and a primary vector of
      Trypanosoma cruzi, the etiological agent of the Chagas disease. Over the past
      century, Rhodnius has been the subject of intense investigations, which have
      contributed to unveil important aspects of metabolism and physiology in insects.
      Recent technological innovations are helping dissect the genetic and molecular
      underpinnings of Rhodnius embryogenesis and organogenesis, thus fostering the use
      of this important species in the fields of developmental and evolutionary
      biology. Rhodnius represents also an excellent system to study development under
      stressful conditions, since the embryo must develop in the presence of a large
      amount of blood-derived reactive oxygen species. With a recently sequenced
      genome, small among other Hemiptera, and the identification of basic elements for
      all classical development pathways, functional studies in this species are
      revealing novel aspects of insect development and evolution. Here we review early
      studies on this model insect and how this paved the way for recent functional
      studies using the kissing bug.

PMID- 28432817
TI  - Factors involved in early polarization of the anterior-posterior axis in the
      milkweed bug Oncopeltus fasciatus.
AB  - The axes of insect embryos are defined early in the blastoderm stage. Genes
      involved in this polarization are well known in Drosophila, but less so in other
      insects, such as the milkweed bug Oncopeltus fasciatus. Using quantitative PCR,
      we looked at differential expression of several candidate genes for early
      anterior-posterior patterning and found that none of them are expressed
      asymmetrically in the early blastoderm. We then used an RNA-Seq approach to
      identify novel candidate genes that might be involved in early polarization in
      Oncopeltus. We focused on transcription factors (TFs) as these are likely to be
      central players in developmental processes. Using both homology and domain based
      identification approaches, we were unable to find any TF encoding transcripts
      that are expressed asymmetrically along the anterior-posterior axis at early
      stages. Using a GO-term analysis of all asymmetrically expressed mRNAs, we found
      an enrichment of genes relating to mitochondrial function in the posterior at the
      earliest studied time-point. We also found a gradual enrichment of transcription
      related activities, giving us a putative time frame for the maternal to zygotic
      transition. Our dataset provides us with a list of new candidate genes in early
      development, which can be followed up experimentally.

PMID- 28432818
TI  - Characterization of decellularized ovine small intestine submucosal layer as
      extracellular matrix-based scaffold for tissue engineering.
AB  - Extracellular matrix-based scaffolds derived from mammalian tissues have been
      used in tissue engineering applications. Among all the tissues, decellularized
      small intestine submucosal layer (SIS) has been recently investigated for its
      exceptional characteristics and biocompatibilities. These investigations have
      been mainly focused on the decellularized porcine SIS; however, there has not
      been any report on ovine SIS (OSIS) layer. In this study, OSIS was decellularized
      and its physical, chemical, and morphological properties were evaluated.
      Decellularization was carried out using chemical reagents and various physical
      conditions. The effects of different conditions were evaluated on histological
      and biomechanical properties, quality of residual DNA, GAPDH gene expression, and
      biocompatibility. Results revealed satisfactory decellularization of OSIS which
      could be due to its thin thickness. Mechanical properties, structural form, and
      glycosaminoglycan contents were preserved in all the decellularized groups. In
      SDS-treated groups, further cells and DNA residues were removed compared to the
      groups treated with Triton X-100 only. No toxicity was observed in all
      treatments, and viability, expansion, and cell proliferation were supported. In
      conclusion, our results suggest that OSIS decellularized scaffold could be
      considered as an appropriate biological scaffold for tissue engineering
      applications. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 106B: 933-944, 2018.

PMID- 28432819
TI  - Identification of bioactive compounds in Shaoyao-Gancao decoction using beta2
      adrenoceptor affinity chromatography.
AB  - Shaoyao-Gancao decoction, a Chinese herbal formula, is composed of Paeoniae Radix
      alba and Glycyrrhiza Radix et rhizoma. It has been widely used to treat muscle
      spasms and asthma. However, little is known about the bioactive components of
      Shaoyao-Gancao decoction. In the present study, the bioactive compounds in water
      extract of Shaoyao-Gancao decoction were separated by the immobilized beta2 
      adrenoceptor affinity column and identified using quadrupole time-of-flight mass
      spectrometry. The affinity constants of the separated compounds that bind to
      beta2 -adrenoceptor were determined by frontal analysis. Compound bioactivity was
      tested in a rat tracheal smooth muscle relaxation assay. We identified the
      bioactive compounds in the water extract of Shaoyao-Gancao decoction that bound
      to the beta2 -adrenoceptor as paeoniflorin and liquiritin. Paeoniflorin and
      liquiritin had only one binding site on the immobilized beta2 -adrenoceptor, and
      the affinity constants were (2.16 +/- 0.10) * 104  M-1 and (2.95 +/- 0.15) * 104 
      M-1 , respectively. Both compounds induced a concentration-dependent relaxation
      of tracheal smooth muscle following K+ -stimulated contraction, and the
      relaxation effects were abrogated by the beta2 -adrenoceptor antagonist, ICI
      118551. Therefore, paeoniflorin and liquiritin are bioactive compounds in Shaoyao
      Gancao decoction and the beta2 -adrenoceptor affinity chromatography is a useful
      tool for identifying potential beta2 -adrenoceptor ligands in natural products
      used in traditional Chinese medicine.

PMID- 28432820
TI  - The impact of small motion on the visualization of coronary vessels and lesions
      in cardiac CT: A simulation study.
AB  - PURPOSE: Coronary x-ray computed tomography angiography (CCTA) is used to non
      invasively assess coronary artery geometry and has, combined with computational
      modeling, demonstrated the potential to identify physiologically significant
      lesions. These measurements require robust and accurate coronary imaging and
      delineation of vessels despite the presence of small motion. This simulation
      study characterizes the impact of small, uncorrected vessel drifts during data
      acquisition on the assessment of vessel intensity, diameter, and shape. METHODS:
      We developed a digital phantom and simulated projection data for a clinical
      scanner geometry for a range of vessel drifts that can occur during relative
      vessel stasis (0 to 2 mm per 360 degrees  gantry rotation) for vessels between
      0.2 and 3.0 mm in diameter (covering 0% through 93% stenosis of a 3 mm vessel).
      In addition to the impact of vessel drift, we evaluated the performance of half
      scan acquisitions (relative to full-scans) over a range of gantry positions. The
      performance of FDK reconstructions was compared to an iterative technique and
      potential improvement in sampling from focal spot deflection and quarter detector
      offset was compared. RESULTS: At rest, vessel intensity and diameter were
      accurately obtained in vessels greater than 1.5 mm with all vessels appearing
      circular in shape (major-to-minor axis ratio ~1). Vessels between 1.5 and 0.2 mm
      in diameter demonstrated a rapid decrease in signal intensity with full width
      half maximum (FWHM) vessel diameters remaining above 0.75 mm as true vessel
      diameter decreased. Uncorrected vessel motion resulted in decreased vessel
      intensity, increased vessel diameter, and distortion of vessel shape. The extent
      of these changes depended on both the position of the gantry as well as the
      reconstruction approach (half- vs. full-scan). FDK reconstruction results
      depended on choice of filter with Ram-Lak results yielding comparable performance
      to an unconstrained iterative reconstruction. Focal spot deflection and quarter
      detector offset did not result in large changes in performance, likely due to the
      high sampling density near the isocenter. CONCLUSIONS: Despite improvement in
      gantry speed and acquisition of coronary images during cardiac phases that have
      relatively stationary vessels, small coronary drifts (0-2 mm per 360 degrees 
      rotation) have been reported and if uncorrected, can present challenges to visual
      grading and computational modeling of stenoses because vessels will appear
      dimmer, larger, and more ellipsoidal in shape. The impact of a particular motion
      depends on the gantry position, the use of half vs. full-scan acquisitions, and
      the reconstruction technique.

PMID- 28432821
TI  - Addition of Hydrogen Peroxide to Groundwater with Natural Iron Induces Water
      Disinfection by Photo-Fenton at Circumneutral pH and other Photochemical Events.
AB  - Samples of natural groundwater (with low turbidity, neutral pH and 0.3 mg L-1
      iron concentration) inoculated with Escherichia coli K-12 were exposed to
      simulated solar light both in the presence and in the absence 10 mg L-1 of H2 O2.
      Results demonstrated that the viability of E. coli (by DVC-FISH) was grounded to
      zero after 360 min of irradiation. This abatement could be caused by the
      oxidative stress induced by .OH radicals or another photo-induced reactive oxygen
      species. Two 23 factorial experimental designs enabled the evaluation of the
      effects of chemical factors on the inactivation of E. coli. The first
      experimental design considered the pH, iron and H2 O2 , while the second
      evaluated the ions fluoride, carbonate and phosphate found in groundwater. pH was
      found to play a key role in the inactivation of E. coli. The best reduction in
      viability was obtained at the lower pH (6.75), while a nonsignificant effect was
      observed when iron or H2 O2 concentrations were raised. At higher concentrations,
      anions, such as carbonate and phosphate, negatively affected the E. coli
      abatement. However, a higher concentration of fluoride accelerated it. In all
      experiments, the pH was observed to rise to values higher than 8.0 units after
      360 min of treatment.

PMID- 28432822
TI  - Focal liver lesions segmentation and classification in nonenhanced T2-weighted
      MRI.
AB  - PURPOSE: To automatically segment and classify focal liver lesions (FLLs) on
      nonenhanced T2-weighted magnetic resonance imaging (MRI) scans using a computer
      aided diagnosis (CAD) algorithm. METHODS: 71 FLLs (30 benign lesions, 19
      hepatocellular carcinomas, and 22 metastases) on T2-weighted MRI scans were
      delineated by the proposed CAD scheme. The FLL segmentation procedure involved
      wavelet multiscale analysis to extract accurate edge information and mean
      intensity values for consecutive edges computed using horizontal and vertical
      analysis that were fed into the subsequent fuzzy C-means algorithm for final FLL
      border extraction. Texture information for each extracted lesion was derived
      using 42 first- and second-order textural features from grayscale value
      histogram, co-occurrence, and run-length matrices. Twelve morphological features
      were also extracted to capture any shape differentiation between classes. Feature
      selection was performed with stepwise multilinear regression analysis that led to
      a reduced feature subset. A multiclass Probabilistic Neural Network (PNN)
      classifier was then designed and used for lesion classification. PNN model
      evaluation was performed using the leave-one-out (LOO) method and receiver
      operating characteristic (ROC) curve analysis. RESULTS: The mean overlap between
      the automatically segmented FLLs and the manual segmentations performed by
      radiologists was 0.91 +/- 0.12. The highest classification accuracies in the PNN
      model for the benign, hepatocellular carcinoma, and metastatic FLLs were 94.1%,
      91.4%, and 94.1%, respectively, with sensitivity/specificity values of 90%/97.3%,
      89.5%/92.2%, and 90.9%/95.6% respectively. The overall classification accuracy
      for the proposed system was 90.1%. CONCLUSIONS: Our diagnostic system using
      sophisticated FLL segmentation and classification algorithms is a powerful tool
      for routine clinical MRI-based liver evaluation and can be a supplement to
      contrast-enhanced MRI to prevent unnecessary invasive procedures.

PMID- 28432823
TI  - #GeriMedJC: The Twitter Complement to the Traditional-Format Geriatric Medicine
      Journal Club.
AB  - Twitter is a public microblogging platform that overcomes physical limitations
      and allows unrestricted participation beyond academic silos, enabling interactive
      discussions. Twitter-based journal clubs have demonstrated growth,
      sustainability, and worldwide communication, using a hashtag (#) to follow
      participation. This article describes the first year of #GeriMedJC, a monthly 1
      hour live, 23-hour asynchronous Twitter-based complement to the traditional
      format geriatric medicine journal club. The Twitter moderator tweets from the
      handle @GeriMedJC; encourages use of #GeriMedJC; and invites content experts,
      study authors, and followers to participate in critical appraisal of medical
      literature. Using the hashtag #GeriMedJC, tweets were categorized according to
      thematic content, relevance to the journal club, and authorship. Third-party
      analytical tools Symplur and Twitter Analytics were used for growth and effect
      metrics (number of followers, participants, tweets, retweets, replies,
      impressions). Qualitative analysis of follower and participant profiles was used
      to establish country of origin and occupation. A semistructured interview of
      postgraduate trainees was conducted to ascertain qualitative aspects of the
      experience. In the first year, @GeriMedJC has grown to 541 followers on six
      continents. Most followers were physicians (43%), two-thirds of which were
      geriatricians. Growth metrics increased over 12 months, with a mean of 121
      tweets, 25 participants, and 105,831 impressions per journal club. Tweets were
      most often related to the article being appraised (87.5%) and ranged in thematic
      content from clinical practice (29%) to critical appraisal (24%) to medical
      education (20%). #GeriMedJC is a feasible example of using social media platforms
      such as Twitter to encourage international and interprofessional appraisal of
      medical literature.

PMID- 28432824
TI  - An analysis of dental development in Pleistocene Homo using skeletal growth and
      chronological age.
AB  - OBJECTIVES: This study takes a new approach to interpreting dental development in
      Pleistocene Homo in comparison with recent modern humans. As rates of dental
      development and skeletal growth are correlated given age in modern humans, using
      age and skeletal growth in tandem yields more accurate dental development
      estimates. Here, I apply these models to fossil Homo to obtain more
      individualized predictions and interpretations of their dental development
      relative to recent modern humans. MATERIALS AND METHODS: Proportional odds
      logistic regression models based on three recent modern human samples (N = 181)
      were used to predict permanent mandibular tooth development scores in five
      Pleistocene subadults: Homo erectus/ergaster, Neanderthals, and anatomically
      modern humans (AMHs). Explanatory variables include a skeletal growth indicator
      (i.e., diaphyseal femoral length), and chronological age. RESULTS: AMHs Lagar
      Velho 1 and Qafzeh 10 share delayed incisor development, but exhibit considerable
      idiosyncratic variation within and across tooth types, relative to each other and
      to the reference samples. Neanderthals Dederiyeh 1 and Le Moustier 1 exhibit
      delayed incisor coupled with advanced molar development, but differences are
      reduced when femoral diaphysis length is considered. Dental development in KNM-WT
      15,000 Homo erectus/ergaster, while advanced for his age, almost exactly matches
      the predictions once femoral length is included in the models. DISCUSSION: This
      study provides a new interpretation of dental development in KNM-WT 15000 as
      primarily reflecting his faster rates of skeletal growth. While the two AMH
      specimens exhibit considerable individual variation, the Neanderthals exhibit
      delayed incisor development early and advanced molar development later in
      ontogeny.

PMID- 28432825
TI  - Small and preterm infants: The shrinking frontier of transcatheter patent ductus
      arteriosus closure.

PMID- 28432826
TI  - Ploidy has little effect on timing early embryonic events in the haplo-diploid
      wasp Nasonia.
AB  - The nucleocytoplasmic (N/C) ratio plays a prominent role in the maternal-to
      zygotic transition (MZT) in many animals. The effect of the N/C ratio on cell
      cycle lengthening and zygotic genome activation (ZGA) has been studied
      extensively in Drosophila, where haploid embryos experience an additional
      division prior to completing cellularization and triploid embryos cellularize
      precociously by one division. In this study, we set out to understand how the
      obligate difference in ploidy in the haplodiploid wasp, Nasonia, affects the MZT
      and which aspects of the Drosophila MZT are conserved. While subtle differences
      in early embryonic development were observed in comparisons among haploid,
      diploid, and triploid embryos, in all cases embryos cellularize at cell cycle 12.
      When ZGA was inhibited, both diploid female, and haploid male, embryos went
      through 12 syncytial divisions and failed to cellularize before dying without
      further divisions. We also found that key players of the Drosophila MZT are
      conserved in Nasonia but have novel expression patterns. Our results suggest that
      zygotically expressed genes have a reduced role in determining the timing of
      cellularization in Nasonia relative to Drosophila, and that a stronger reliance
      on a maternal timer is more compatible with species where variations in embryonic
      ploidy are obligatory.

PMID- 28432827
TI  - Parenting stress and its association with perceived agreement about the
      disclosure decision in parents following donor conception.
AB  - INTRODUCTION: For many donor-conceiving heterosexual parents, the process of
      deciding whether and what to tell children about their genetic origin is
      challenging. We hypothesized that incomplete couple agreement about disclosure
      could be associated with parenting stress. The aim of the study was to
      investigate: (1) parenting stress levels among heterosexual parents of young
      children following gamete donation and (2) whether parenting stress is related to
      perceived agreement about disclosure of the donor conception to the children.
      MATERIAL AND METHODS: This study is part of the longitudinal multicenter Swedish
      Study on Gamete Donation and included a total of 213 heterosexual parents with
      children aged 1-4 years following oocyte donation (n = 103) and sperm donation (n
      = 110). Parents individually completed a questionnaire that included validated
      instruments on parenting stress (SPSQ) and relationship quality (ENRICH), as well
      as a study-specific measure on disclosure agreement. Multiple regression analysis
      was applied. RESULTS: Incomplete couple agreement on disclosure to the children
      was not statistically significantly associated with increased levels of parenting
      stress. Relationship satisfaction consistently and significantly accounted for
      variation in parenting stress levels, indicating that relationship satisfaction
      had a buffering impact on parenting stress. CONCLUSIONS: Parental stress does not
      appear to be negatively influenced by incomplete couple agreement about
      disclosure to children. As children grow up, reaching agreement about what to
      tell the child about the donor conception might become more relevant for couples'
      stress related to parenthood.

PMID- 28432829
TI  - Trabecular mapping: Leveraging geometric morphometrics for analyses of trabecular
      structure.
AB  - OBJECTIVES: Trabecular microstructure of limb bone epiphyses has been used to
      elucidate the relationship between skeletal form and behavior among mammals. Such
      studies have often relied on the analysis of a single volume of interest (VOI).
      Here we present a method for evaluating variation in bone microstructure across
      articular surfaces by leveraging sliding semilandmarks. METHODS: Two samples were
      used to demonstrate the proposed methodology and test the hypothesis that
      microstructural variables are homogeneously distributed: tali from two ape genera
      (Pan and Pongo, n = 9) and modern human distal femora (n = 10). Sliding
      semilandmarks were distributed across articular surfaces and used to locate the
      position of multiple VOIs immediately deep to the cortical shell. Trabecular bone
      properties were quantified using the BoneJ plugin for ImageJ. Nonparametric
      MANOVA tests were used to make group comparisons and differences were explored
      using principal components analysis and visualized using color maps. RESULTS:
      Tests reveal that trabecular parameters are not distributed homogeneously and
      identify differences between chimpanzee and orangutan tali with regards to
      trabecular spacing and degree of anisotropy, with chimpanzee tali being more
      anisotropic and having more uniformly spaced trabeculae. Human males and females
      differed in the pattern of trabecular spacing with males having more uniform
      trabecular spacing across the joint surface. CONCLUSIONS: The proposed procedure
      quantifies variation in trabecular bone parameters across joint surfaces and
      allows for meaningful statistical comparisons between groups of interest.
      Consequently it holds promise to help elucidate links between trabecular bone
      structure and animal behavior.

PMID- 28432828
TI  - Quantitative contrast-enhanced spectral mammography based on photon-counting
      detectors: A feasibility study.
AB  - PURPOSE: To investigate the feasibility of accurate quantification of iodine mass
      thickness in contrast-enhanced spectral mammography. MATERIALS AND METHODS: A
      computer simulation model was developed to evaluate the performance of a photon
      counting spectral mammography system in the application of contrast-enhanced
      spectral mammography. A figure-of-merit (FOM), which was defined as the
      decomposed iodine signal-to-noise ratio (SNR) with respect to the square root of
      the mean glandular dose (MGD), was chosen to optimize the imaging parameters, in
      terms of beam energy, splitting energy, and prefiltrations for breasts of various
      thicknesses and densities. Experimental phantom studies were also performed using
      a beam energy of 40 kVp and a splitting energy of 34 keV with 3 mm Al
      prefiltration. A two-step calibration method was investigated to quantify the
      iodine mass thickness, and was validated using phantoms composed of a mixture of
      glandular and adipose materials, for various breast thicknesses and densities.
      Finally, the traditional dual-energy log-weighted subtraction method was also
      studied as a comparison. The measured iodine signal from both methods was
      compared to the known value to characterize the quantification accuracy and
      precision. RESULTS: The optimal imaging parameters, which lead to the highest
      FOM, were found at a beam energy between 42 and 46 kVp with a splitting energy at
      34 keV. The optimal tube voltage decreased as the breast thickness or the Al
      prefiltration increased. The proposed quantification method was able to measure
      iodine mass thickness on phantoms of various thicknesses and densities with high
      accuracy. The root-mean-square (RMS) error for cm-scale lesion phantoms was
      estimated to be 0.20 mg/cm2 . The precision of the technique, characterized by
      the standard deviation of the measurements, was estimated to be 0.18 mg/cm2 . The
      traditional weighted subtraction method also predicted a linear correlation
      between the measured signal and the known iodine mass thickness. However, the
      correlation slope and offset values were strongly dependent on the total breast
      thickness and density. CONCLUSION: The results of this study suggest that iodine
      mass thickness for cm-scale lesions can be accurately quantified with contrast
      enhanced spectral mammography. The quantitative information can potentially
      improve the differential power for malignancy.

PMID- 28432830
TI  - Prevalence of and risk factors for symptomatic urinary tract infection after
      endoscopic incision for the treatment of ureterocele in children.
AB  - OBJECTIVE: To clarify the impact of endoscopic incision (EI) for ureterocele as
      an initial procedure, by performing a retrospective chart review, focusing on the
      prevalence of and risk factors for symptomatic urinary tract infection (UTI)
      after EI. MATERIALS AND METHODS: In the present study we included children with
      ureterocele, managed between September 1994 and April 2016, who were observed
      conservatively without additional surgical management after EI. Ureterocele was
      categorized as intravesical or ectopic. Symptomatic UTI was defined as either
      recurrent non-febrile or febrile UTI. The prevalence of and risk factors for
      symptomatic UTI were analysed using Cox proportional hazard models or Kaplan
      Meier curves, and the log-rank test. RESULTS: A total of 36 children met the
      inclusion criteria. The median age of the participants at EI was 8.9 months.
      Eleven children had symptomatic UTIs (febrile, n = 9; recurrent non-febrile, n =
      2) during the median follow-up of 75.5 months. Initial symptomatic UTI in each
      child occurred <25 months after EI. The symptomatic UTI-free rate after EI was
      65.6%. The risk factors for symptomatic UTI were female gender, duplex system,
      ectopic ureterocele, and unchanged hydronephrosis after EI. CONCLUSIONS: The
      present study determined the critical period and risk factors for symptomatic UTI
      after EI for the treatment of ureterocele. The results suggest that when
      conservative management is indicated after EI, patients, especially those with
      risk factors, should be followed carefully at least for 25 months after EI for
      symptomatic UTI.

PMID- 28432831
TI  - Oncopeltus fasciatus as an evo-devo research organism.
AB  - The large milkweed bug Oncopeltus fasciatus was one of the main study insects for
      a range of biological questions throughout much of the 20th century. Its
      importance waned with the introduction of Drosophila melanogaster as a genetic
      model organism. The evo-devo revolution of the turn of the century re-introduced
      Oncopeltus into the scientific community, and it has proved increasingly useful,
      mostly within a comparative context for evolution driven research. The last few
      years have seen a number of significant contributions to our understanding of the
      evolution of developmental processes in insects, and in arthropods in general,
      arise from work on Oncopeltus. This review presents some of the key studies and
      shows how they have provided new insights into evolutionary questions. The advent
      of whole genome sequencing and genome editing techniques is reducing the gap
      between Drosophila and (re-)emerging systems such as Oncopeltus. We expect that
      the ease of work on Oncopeltus and its pivotal phylogenetic position will
      contribute to the expansion of its use within the evo-devo community and more
      broadly in arthropod research.

PMID- 28432832
TI  - Profiling microRNA from nephrectomy and biopsy specimens: predictors of
      progression and survival in clear cell renal cell carcinoma.
AB  - OBJECTIVE: To identify microRNA (miRNA) characteristic of metastatic clear cell
      renal cell carcinoma (ccRCC) and those indicative of cancer-specific survival
      (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA
      panel could differentiate benign from ccRCC tissue. MATERIALS AND METHODS: RNA
      was isolated from nephrectomy and kidney biopsy specimens (n = 156 and n = 46,
      respectively). Samples were grouped: benign, non-progressive, and progressive
      ccRCC. MiRNAs were profiled by microarray and validated by quantitative reverse
      transcription-polymerase chain reaction. Biomarker signatures were developed to
      predict cancer status in nephrectomy and biopsy specimens. CSS was examined using
      Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Microarray analysis
      revealed 20 differentially expressed miRNAs comparing non-progressive with
      progressive tumours. A biomarker signature validated in nephrectomy specimens had
      a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and
      ccRCC specimens. A second signature differentiated non-progressive vs progressive
      ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers
      also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b
      5p, and -223-3p were associated with CSS. CONCLUSION: This study identified
      miRNAs differentially expressed in ccRCC samples; as well as those correlating
      with CSS. Biomarkers identified in this study have the potential to identify
      patients who are likely to have progressive ccRCC, and although preliminary,
      these results may aid in differentiating aggressive and indolent ccRCC based on
      biopsy specimens.

PMID- 28432833
TI  - Cellular and humoral immunity after vaccination or natural mumps infection.
AB  - BACKGROUND: This study measured cell-mediated immunity (CMI) and serum antibody
      to clarify the basis of breakthrough after vaccination and reinfection after
      mumps. METHODS: From a pool of 54 college students, 17 seronegative subjects and
      14 subjects with intermediate level of antibodies against mumps were vaccinated
      with a monovalent mumps vaccine, and CMI was assessed using interferon-gamma
      release assay. RESULTS: CMI positivity according to pre-existing antibody level,
      defined as titer <2.0 index units, negative; 2.0-3.9 index units, intermediate;
      and >=4.0 index units, positive, was 8/17 (47.1%), 9/14 (64.3%) and 19/23 (82.6%)
      before vaccination, respectively. Of the 17 seronegative subjects, seven (41.2%)
      had a history of vaccination and/or natural infection, four (57.1%) of whom were
      CMI positive or intermediate. Ten (71%) of 14 subjects with intermediate antibody
      level had a history of vaccination or natural infection, eight (80%) of whom were
      CMI positive or intermediate. After vaccination the interferon (IFN)-gamma and
      antibody titers increased significantly, but seven (41.2%) of the 17 seronegative
      subjects and 13 (92.9%) of the 14 intermediate-level subjects tested positive for
      both antibody and CMI. In a comparison of the natural infection group (confirmed
      as IgG seropositive and/or CMI positive without vaccination) versus the
      vaccination group, IgG antibody titer (mean +/- SD) was 14.4 +/- 8.0 versus 3.6
      +/- 2.4 index units (P < 0.01) and IFN-gamma was 122.7 +/- 90.0 pg/mL versus 59.5
      +/- 37.8 pg/mL (P > 0.05), respectively. CONCLUSION: Vaccination or even natural
      mumps infection did not always induce both cellular and humoral immunity.

PMID- 28432834
TI  - Molecular control of gut formation in the spider Parasteatoda tepidariorum.
AB  - The development of a digestive system is an essential feature of bilaterians.
      Studies of the molecular control of gut formation in arthropods have been studied
      in detail in the fruit fly Drosophila melanogaster. However, little is known in
      other arthropods, especially in noninsect arthropods. To better understand the
      evolution of arthropod alimentary system, we investigate the molecular control of
      gut development in the spider Parasteatoda tepidariorum (Pt), the primary
      chelicerate model species for developmental studies. Orthologs of the ectodermal
      genes Pt-wingless (Pt-wg) and Pt-hedgehog (Pt-hh), of the endodermal genes, Pt
      serpent (Pt-srp) and Pt-hepatocyte-nuclear factor-4 (Pt-hnf4) and of the
      mesodermal gene Pt-twist (Pt-twi) are expressed in the same germ layers during
      spider gut development as in D. melanogaster. Thus, our expression data suggest
      that the downstream molecular components involved in gut development in
      arthropods are conserved. However, Pt-forkhead (Pt-fkh) expression and function
      in spiders is considerably different from its D. melanogaster ortholog. Pt-fkh is
      expressed before gastrulation in a cell population that gives rise to endodermal
      and mesodermal precursors, suggesting a possible role for this factor in
      specification of both germ layers. To test this hypothesis, we knocked down Pt
      fkh via RNA interference. Pt-fkh RNAi embryos not only fail to develop a proper
      gut, but also lack the mesodermal Pt-twi expressing cells. Thus, in spiders Pt
      fkh specifies endodermal and mesodermal germ layers. We discuss the implications
      of these findings for the evolution and development of gut formation in
      Ecdysozoans.

PMID- 28432835
TI  - Detection of soft-tissue abscess: Comparison of diffusion-weighted imaging to
      contrast-enhanced MRI.
AB  - PURPOSE: To compare the diagnostic performances of diffusion-weighted imaging
      (DWI)-combined magnetic resonance imaging (MRI) performed without intravenous
      contrast material with gadolinium contrast material-enhanced (CE) MRI for
      diagnosing soft-tissue abscesses. MATERIALS AND METHODS: In all, 119 patients
      (mean age: 56 years) with skin and soft-tissue infection who underwent contrast
      enhanced MRI with DWI (b = 0-800) were included. Two readers independently
      reviewed both image sets-nonenhanced conventional MR images (NECI)+DWI, and
      NECI+contrast enhanced fat-suppressed T1 -weighted imaging (CEFST1 )-for the
      presence of abscess. To compare the diagnostic performance for diagnosing abscess
      between NECI+DWI, and NECI+CEFST1 , McNemar tests for sensitivity and
      specificity, and areas under the receiver-operating characteristic curves (AUC)
      analyses, were performed. Interobserver agreements (kappa) were calculated for
      each image set. RESULTS: Forty of 119 patients were confirmed with abscess.
      Sensitivity and specificity were 90.0% and 88.6% for NECI+DWI, and 82.5% and
      89.9% for NECI+CEFST1 in reader 1, whereas 77.5% and 88.6% for NECI+DWI, and
      80.0% and 84.8% for NECI+CEFST1 in reader 2, respectively. There was no
      significant difference in sensitivities and specificities between NECI+DWI and
      NECI+CEFST1 (reader 1: P = 0.453, P = 0.999, reader 2: P = 0.999, P = 0.453,
      respectively). Likewise, AUC analyses demonstrated no significant difference
      between NECI+DWI and NECI+CEFST1 (P = 0.53 in reader 1, P = 0.97 in reader 2).
      Interobserver agreement between the two readers was substantial in both image
      sets: 0.80 (NECI+DWI), and 0.76 (NECI+CEFST1 ). CONCLUSION: Noncontrast-enhanced
      MRI with DWI has comparable diagnostic performance to contrast-enhanced MRI for
      diagnosing soft-tissue abscesses. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage
      2 J. Magn. Reson. Imaging 2018;47:60-68.

PMID- 28432836
TI  - Autoimmune hepatitis: From current knowledge and clinical practice to future
      research agenda.
AB  - Autoimmune hepatitis is a chronic inflammatory liver disease. Unknown triggers
      lead to a mainly T cell-mediated immune response targeting the liver, the main
      auto-antigen of which has not been identified yet. The diagnosis of autoimmune
      hepatitis is based on the elevation of immunoglobulin G/hypergammaglobulinemia,
      detection of characteristic autoantibodies as well as a typical pattern on liver
      histology. Exclusion of other causes of hepatitis and response to
      immunosuppressive treatment support the diagnosis of autoimmune hepatitis. The
      mainstay of autoimmune hepatitis treatment has, from its first description to the
      current time, consisted of predniso(lo)ne to induce remission, in combination
      with azathioprine, which is used to maintain it. Nonetheless, side effects and
      non-response with ongoing inflammation despite standard therapy demand treatment
      alternatives. Only through a better understanding of the pathogenesis of
      autoimmune hepatitis can a more selective and effective treatment be offered to
      patients in the future. Until this goal is reached, improvement of diagnostic
      approaches and optimization of current therapy rank highest on the research
      agenda for autoimmune hepatitis.

PMID- 28432838
TI  - Are poikilothermic animals real hosts for Toxoplasma gondii?
AB  - The protozoan Toxoplasma gondii is believed to be a common parasite of almost all
      endothermic animals and humans. However, recent reports of toxoplasmosis in
      marine mammals raise concern that cold-blooded animals may also be a potential
      source of T. gondii infection. The article discusses the presence of T. gondii in
      aquatic and terrestrial poikilothermic animals, which may be important elements
      in the transmission of the parasite.

PMID- 28432839
TI  - Aeromonas sobria serine protease (ASP): a subtilisin family endopeptidase with
      multiple virulence activities.
AB  - Aeromonas sobria serine protease (ASP) is secreted from Aeromonas sobria, a
      pathogen causing gastroenteritis and sepsis. ASP resembles Saccharomyces
      cerevisiae Kex2, a member of the subtilisin family, and preferentially cleaves
      peptide bonds at the C-terminal side of paired basic amino acid residues; also
      accepting unpaired arginine at the P1 site. Unlike Kex2, however, ASP lacks an
      intramolecular chaperone N-terminal propeptide, instead utilizes the external
      chaperone ORF2 for proper folding, therefore, ASP and its homologues constitute a
      new subfamily in the subtilisin family. Through activation of the
      kallikrein/kinin system, ASP induces vascular leakage, and presumably causes
      edema and septic shock. ASP accelerates plasma clotting by alpha-thrombin
      generation from prothrombin, whereas it impairs plasma clottability by fibrinogen
      degradation, together bringing about blood coagulation disorder that occurs in
      disseminated intravascular coagulation, a major complication of sepsis. From
      complement C5 ASP liberates C5a that induces neutrophil recruitment and
      superoxide release, and mast cell degranulation, which are associated with pus
      formation, tissue injury and diarrhea, respectively. Nicked two-chain ASP also
      secreted from A. sobria is more resistant to inactivation by alpha2-macroglobulin
      than single-chain ASP, thereby raising virulence activities. Thus, ASP is a
      potent virulence factor and may participate in the pathogenesis of A. sobria
      infection.

PMID- 28432840
TI  - Detection of EGFR mutations in patients with non-small cell lung cancer by high
      resolution melting. Comparison with other methods.
AB  - BACKGROUND: The discovery of mutations in the epidermal growth factor receptor
      gene (EGFR) related to the clinical response to tyrosine kinase inhibitors, has
      transformed the management of non-small cell lung cancer (NSCLC). Several methods
      have been developed for determination of mutations in EGFR, with different
      sensitivity and potential ability to detect a different number of mutations.
      METHODS: We developed a screening method by high resolution melting (HRM) to
      detect EGFR mutations, and compared the results of 123 fixed in formalin and
      paraffin embedded (FFPE) tumor tissue samples with the detection of mutations by
      allele-specific PCR. In samples with discordant results, Sanger and massive
      parallel sequencing (MPS) were additionally performed. RESULTS: Eight samples
      showed discordant results between both methods. Three samples with negative
      results by allele specific PCR and positive by HRM were confirmed by Sanger
      sequencing (p.S768I+p.V769L, T751_I759del and p.E709K+p.G719A; patients 1, 3 and
      4, respectively). One sample with a negative result by HRM, and positive by
      allele specific PCR (p.T790M; patient 2), was confirmed by Sanger sequencing.
      Additionally, two positive samples for a deletion in exon 19 by allele-specific
      PCR, were negative by Sanger sequencing and HRM (patients 2 and 5) and finally,
      two samples were negative by allele-specific PCR and positive by HRM and Sanger
      sequencing due to synonymous variants in exon 21. CONCLUSIONS: HRM is a good
      method for mutational screening in EGFR. It is able to detect any change in the
      sequence of exons 18-21, providing high cost/effectiveness, but samples with low
      tumor burden may produce false negatives results.

PMID- 28432841
TI  - Comparison of pneumatic tube system with manual transport for routine chemistry,
      hematology, coagulation and blood gas tests.
AB  - BACKGROUND: The pneumatic tube system (PTS) is commonly used in modern clinical
      laboratories to provide quick specimen delivery. However, its impact on sample
      integrity and laboratory testing results are still debatable. In addition, each
      PTS installation and configuration is unique to its institution. We sought to
      validate our Swisslog PTS by comparing routine chemistry, hematology, coagulation
      and blood gas test results and sample integrity indices between duplicate samples
      transported either manually or by PTS. METHODS: Duplicate samples were delivered
      to the core laboratory manually by human courier or via the Swisslog PTS. Head-to
      head comparisons of 48 routine chemistry, hematology, coagulation and blood gas
      laboratory tests, and three sample integrity indices were conducted on 41 healthy
      volunteers and 61 adult patients. RESULTS: The PTS showed no impact on sample
      hemolysis, lipemia, or icterus indices (all p<0.05). Although alkaline
      phosphatase, total bilirubin and hemoglobin reached statistical significance
      (p=0.009, 0.027 and 0.012, respectively), all had very low average bias which
      ranged from 0.01% to 2%. Potassium, total hemoglobin and percent deoxyhemoglobin
      were statistically significant for the neonatal capillary tube study (p=0.011,
      0.033 and 0.041, respectively) but no biases greater than +/-4% were identified
      for these parameters. All observed differences of these 48 laboratory tests were
      not clinically significant. CONCLUSIONS: The modern PTS investigated in this
      study is acceptable for reliable sample delivery for routine chemistry,
      hematology, coagulation and blood gas (in syringe and capillary tube) laboratory
      tests.

PMID- 28432842
TI  - Low-grade inflammation and tryptophan-kynurenine pathway activation are
      associated with adverse cardiac remodeling in primary hyperparathyroidism: the
      EPATH trial.
AB  - BACKGROUND: Primary hyperparathyroidism (pHPT) is associated with low-grade
      inflammation, left ventricular hypertrophy and increased cardiovascular
      mortality, but the association between inflammatory markers and parameters of
      adverse cardiac remodeling is unknown. We investigated the relationship between C
      reactive protein (CRP), the essential amino acid tryptophan and its pro
      inflammatory derivatives kynurenine and quinolinic acid (QUIN) with
      echocardiographic parameters. METHODS: Cross-sectional baseline data from the
      "Eplerenone in Primary Hyperparathyroidism" trial were analyzed. Patients with
      any acute illness were excluded. We assessed associations between CRP, serum
      levels of tryptophan, kynurenine and QUIN and left ventricular mass index (LVMI),
      left atrial volume index (LAVI) and E/e'. RESULTS: Among 136 subjects with pHPT
      (79% females), 100 (73%) had arterial hypertension and the prevalence of left
      ventricular hypertrophy was 52%. Multivariate linear regression analyses with
      LVMI, LAVI and E/e' as respective dependent variables, and C-reactive protein and
      tryptophan, kynurenine and QUIN as respective independent variables were
      performed. Analyses were adjusted for age, sex, blood pressure, parathyroid
      hormone, calcium and other cardiovascular risk factors. LVMI was independently
      associated with CRP (adjusted beta-coefficient=0.193, p=0.030) and QUIN
      (beta=0.270, p=0.007), but not kynurenine. LAVI was related with CRP (beta=0.315,
      p<0.001), kynurenine (beta=0.256, p=0.005) and QUIN (beta=0.213, p=0.044). E/e'
      was related with kynurenine (beta=0.221, p=0.022) and QUIN (beta=0.292, p=0.006).
      Tryptophan was not associated with any of the remodeling parameters. [Correction
      added after online publication (22 April 2017: The sentence "Among 136 subjects
      with pHPT (79% females), 100 (73%) had left ventricular hypertrophy." was
      corrected to "Among 136 subjects with pHPT (79% females), 100 (73%) had arterial
      hypertension and the prevalence of left ventricular hypertrophy was 52%."]
      Conclusions: Cardiac remodeling is common in pHPT and is associated with low
      grade inflammation and activation of the tryptophan-kynurenine pathway. The
      potential role of kynurenine and QUIN as cardiovascular risk factors may be
      further investigated in future studies.

PMID- 28432843
TI  - Vitamin B1 in critically ill patients: needs and challenges.
AB  - BACKGROUND: Thiamine has a crucial role in energy production, and consequently
      thiamine deficiency (TD) has been associated with cardiac failure, neurological
      disorders, oxidative stress (lactic acidosis and sepsis) and refeeding syndrome
      (RFS). This review aims to explore analytical methodologies of thiamine compound
      quantification and highlight similarities, variances and limitations of current
      techniques and how they may be relevant to patients. CONTENT: An electronic
      search of Medline, PubMed and Embase databases for original articles published in
      peer-reviewed journals was conducted. MethodsNow was used to search for published
      analytical methods of thiamine compounds. Keywords for all databases included
      "thiamine and its phosphate esters", "thiamine methodology" and terms related to
      critical illness. Enquiries were also made to six external quality assurance
      (EQA) programme organisations for the inclusion of thiamine measurement. SUMMARY:
      A total of 777 published articles were identified; 122 were included in this
      review. The most common published method is HPLC with florescence detection. Two
      of the six EQA organisations include a thiamine measurement programme, both
      measuring only whole-blood thiamine pyrophosphate (TPP). No standard measurement
      procedure for thiamine compound quantification was identified. OUTLOOK: Overall,
      there is an absence of standardisation in measurement methodologies for thiamine
      in clinical care. Consequently, multiple variations in method practises are
      prohibiting the comparison of study results as they are not traceable to any
      higher order reference. Traceability of certified reference materials and
      reference measurement procedures is needed to provide an anchor to create the
      link between studies and help bring consensus on the clinical importance of
      thiamine.

PMID- 28432844
TI  - Evaluating new HbA1c methods for adoption by the IFCC and NGSP reference networks
      using international quality targets.
AB  - BACKGROUND: As a reference laboratory for HbA1c, it is essential to have accurate
      and precise HbA1c methods covering a range of measurement principles. We report
      an evaluation of the Abbott Enzymatic (Architect c4000), Roche Gen.3 HbA1c (Cobas
      c513) and Tosoh G11 using different quality targets. METHODS: The effect of
      hemoglobin variants, other potential interferences and the performance in
      comparison to both the International Federation of Clinical Chemistry and
      Laboratory Medicine (IFCC) and the National Glycohemoglobin Standardization
      Program (NGSP) reference systems was assessed using certified evaluation
      protocols. RESULTS: Each of the evaluated HbA1c methods had CVs <3% in SI units
      and <2% in NGSP units at 46 mmol/mol (6.4%) and 72 mmol/mol (8.7%) and passed the
      NGSP criteria when compared with six secondary reference measurement procedures
      (SRMPs). Sigma was 8.6 for Abbott Enzymatic, 3.3 for Roche Cobas c513 and 6.9 for
      Tosoh G11. No clinically significant interference was detected for the common Hb
      variants for the three methods. CONCLUSIONS: All three methods performed well and
      are suitable for clinical application in the analysis of HbA1c. Partly based on
      the result of this study, the Abbott Enzymatic method on the Architect c4000 and
      the Roche Gen.3 HbA1c on the Cobas c513 are now official, certified IFCC and NGSP
      SRMPs in the IFCC and NGSP networks. Sigma metrics quality criteria presented in
      a graph distinguish between good and excellent performance.

PMID- 28432845
TI  - Effect of age on serum prostate-specific antigen in women.

PMID- 28432846
TI  - Pathological Internet use, cyberbullying and mobile phone use in adolescence: a
      school-based study in Greece.
AB  - Purpose This study investigated the prevalence of Internet addiction (IA) and
      cyberbullying and examined profiles of adolescents with increased risk to develop
      pathological behaviors. Methods In this cross-sectional, school-based study, 8053
      students of 30 middle and 21 high schools (12-18 years old) were invited to
      participate, based on a multistage stratified random sampling technique. The
      Internet aiddiction test (IAT) was used along with information on socio
      demographics, Internet activities and cyberbullying experience. Results Five
      thousand five hundred and ninety students participated (response rate 69.4%).
      Pathological Internet use (IAT >=50) was found in 526 (10.1%), while 403 (7.3%)
      experienced cyberbullying as victims and 367 (6.6%) as perpetrators during the
      last year. In multivariable models, the odds of IA increased with online hours on
      mobile phones and Internet use during weekends, Internet cafe visits, chatrooms
      usage and engagement in cyberbullying. Cyberbullying victims were more likely to
      be older, female, Facebook and chatrooms users, while perpetrators were more
      likely to be male, older Internet users and fans of pornographic sites. A
      perpetrator was significantly more likely to have also been a victim [odds ratio
      (OR) = 5.51, confidence interval (CI): 3.92-7.74]. Hours of daily Internet use on
      a mobile phone was independently associated with IA and cyberbullying (OR) 1.41,
      95% CI 1.30, 1.53 and OR 1.11, 95% CI 1.01, 1.21, respectively. Conclusions
      Cyberbullying is associated with IA and the hours spent online on a mobile phone
      affected both conditions. The increasing Internet access through mobile phones or
      other devices should be accompanied by the appropriate education of both parents
      and adolescents on safe Internet use.

PMID- 28432847
TI  - Genotype-phenotype correlation in paediatric pheochromocytoma and paraganglioma:
      a single centre experience from India.
AB  - BACKGROUND: Data on genotype-phenotype correlation in children is limited. Hence,
      we studied the prevalence of germline mutations and genotype-phenotype
      correlation in children with pheochromocytoma (PCC)/paraganglioma (PGL) and
      compared it with adult PCC/PGL cohort. METHODS: A total of 121 consecutive,
      unrelated, index PCC/PGL patients underwent genetic testing for five PCC/PGL
      susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) and were evaluated for
      clinical diagnosis of neurofibromatosis type1 (NF1). RESULTS: Thirty patients (12
      boys, 18 girls) presented at <=20 years of age (mean age of 15.9+/-3.8 years).
      Children were more frequently symptomatic and more frequently had bilateral PCC
      than adults. Fourteen (46.7%) PCC/PGL children had germline mutations (VHL 10
      [33.3%], SDHB 2 [6.6%], and SDHD 2 [6.6%]). Overall germline mutations (46.7% vs.
      26.4%, p=0.04) and VHL mutations (33.3% vs. 10.9%, p=0.026) were significantly
      more common in children than in adults. In children with VHL mutations, bilateral
      PCC were more frequent than in adults with VHL mutations. Within the paediatric
      cohort, bilateral PCC (60% vs. 5%, p=0.002), PCC+sPGL (30% vs. 0%, p=0.03) and
      occurrence of a second PCC/PGL (30% vs. 0%, p=0.03) were significantly more
      frequent among children with VHL mutations than others. CONCLUSIONS: All PCC/PGL
      children should be screened for germline mutations with first priority for VHL
      gene testing. Paediatric PCC/PGL patients with VHL mutations should be thoroughly
      evaluated for bilateral PCC and PCC+sPGL at initial presentation and closely
      followed up for occurrence of a second PCC/PGL.

PMID- 28432848
TI  - Trends in the prevalence of extreme obesity among Korean children and adolescents
      from 2001 to 2014.
AB  - BACKGROUND: We assessed nationwide trends in extreme obesity prevalence and its
      impact on metabolic syndrome in Korean youth. METHODS: Data from 19,593 youth
      (10,271 boys) aged 2-19 were obtained from the Korean National Health and
      Nutrition Examination Surveys (2001-2014). The prevalence of extreme obesity and
      the odds ratio of metabolic syndrome were calculated. Questionnaires on body
      weight perceptions and weight control behaviors were administered. RESULTS: The
      prevalence of extreme obesity increased significantly among boys (p<0.05). The
      odds ratios of extreme obesity on metabolic syndrome compared with obesity were
      3.781 and 1.979 in boys and girls, respectively. Obese teenage girls with
      appropriate weight perception attempted to lose weight more frequently than obese
      teenage boys did. CONCLUSIONS: Although the prevalence of childhood obesity in
      Korea was similar since early 2000s, extreme obesity prevalence has increased,
      especially among teenage boys. Considering greater morbidity risks, preventing
      progression to extreme obesity is crucial.

PMID- 28432849
TI  - Upper extremity deep venous thrombosis and stenosis after implantation of
      pacemakers and defibrillators; A prospective study.
AB  - BACKGROUND: Obstruction of the access vein following cardiac pacemaker and
      defibrillator implantation is a common complication. However, the exact incidence
      and contributing risk factors are unknown. The aim of this study is to determine
      the incidence and analyze the contribution of each risk factor. METHODS: 57
      consecutive patients candidate for their first transvenous pacemaker, implantable
      cardioverter-defibrillator (ICD), or cardiac resynchronization therapy device
      implantation were enrolled. After implantation, venography of the ipsilateral
      peripheral arm was performed. Patients underwent their second venography after
      the follow-up period of 3 to 6 months. RESULTS: 42 patients (13 females, mean age
      59.71 +/- 12.33) completed the study. The followup venography showed significant
      venous obstruction (more than 50%) in 9 (21%) patients, but in none of the
      individuals, venography revealed total occlusion of the veins. Patients with
      obstruction had more leads in their veins (2.56 +/- 0.53 vs 1.58 +/- 0.71, P =
      0.001). Venous obstruction was significantly more prevalent in patients with
      implanted cardiac resynchronization therapy device compared with an ICD or
      pacemaker (p = 0. 01). Age, gender, diabetes mellitus, hypertension, ischemic
      heart disease and antiplatelet consumption did not reveal any other contribution
      to the risk of thrombosis. In multivariate analysis, total lead number was a
      positive predictor for venous occlusion (P = 0.015, OR:19.2, and CI: 1.7-207.1).
      CONCLUSION: Venous obstruction is relatively frequent after pacemaker or ICD
      implantation. This study also shows that pacemaker and ICD leads have a similar
      risk for lead-related venous obstruction. However, patients with multiple leads
      are associated with an increased risk.

PMID- 28432850
TI  - A detailed experimental study of a DNA computer with two endonucleases.
AB  - Great advances in biotechnology have allowed the construction of a computer from
      DNA. One of the proposed solutions is a biomolecular finite automaton, a simple
      two-state DNA computer without memory, which was presented by Ehud Shapiro's
      group at the Weizmann Institute of Science. The main problem with this computer,
      in which biomolecules carry out logical operations, is its complexity -
      increasing the number of states of biomolecular automata. In this study, we
      constructed (in laboratory conditions) a six-state DNA computer that uses two
      endonucleases (e.g. AcuI and BbvI) and a ligase. We have presented a detailed
      experimental verification of its feasibility. We described the effect of the
      number of states, the length of input data, and the nondeterminism on the
      computing process. We also tested different automata (with three, four, and six
      states) running on various accepted input words of different lengths such as ab,
      aab, aaab, ababa, and of an unaccepted word ba. Moreover, this article presents
      the reaction optimization and the methods of eliminating certain biochemical
      problems occurring in the implementation of a biomolecular DNA automaton based on
      two endonucleases.

PMID- 28432851
TI  - Fungal production of the polysaccharide pullulan from a plant hydrolysate.
AB  - The ability of the fungus Aureobasidium pullulans ATCC 42023 to produce pullulan
      from hydrolysates of the native grass known as prairie cordgrass was investigated
      and examined relative to polysaccharide and cell biomass production, yield, and
      pullulan content of the polysaccharide. A pullulan concentration of 9.7 g l-1 and
      yield of 0.78 g g-1 was produced by ATCC 42023 when grown for 168 h at 30 degrees
      C on a phosphate-buffered hydrolysate. The highest biomass level of 7.7 g l-1 was
      produced by ATCC 42023 after 168 h on a hydrolysate-containing complete medium.
      The pullulan content of the polysaccharide produced by ATCC 42023 after 168 h on
      the hydrolysate medium alone was 77%. Unlike what has been observed for other
      biomass substrates, a polysaccharide with a high pullulan content can be produced
      at a relatively high yield by a fungus grown on a grass hydrolysate indicating
      that pullulan could be produced using a biomass-based process.

PMID- 28432852
TI  - Correlation Between Expression of High Temperature Requirement Serine Protease A1
      (HtrA1) in Nucleus Pulposus and T2 Value of Magnetic Resonance Imaging.
AB  - BACKGROUND Degrading enzymes play an important role in the process of disc
      degeneration. The objective of this study was to investigate the correlation
      between the expression of high temperature requirement serine protease A1 (HtrA1)
      in the nucleus pulposus and the T2 value of the nucleus pulposus region in
      magnetic resonance imaging (MRI). MATERIAL AND METHODS Thirty-six patients who
      had undergone surgical excision of the nucleus pulposus were examined by MRI
      before surgery. Pfirrmann grading of the target intervertebral disc was performed
      according to the sagittal T2-weighted imaging, and the T2 value of the target
      nucleus pulposus was measured according to the median sagittal T2 mapping. The
      correlation between the Pfirrmann grade and the T2 value was analyzed. The
      expression of HtrA1 in the nucleus pulposus was analyzed by RT-PCR and Western
      blot. The correlation between the expression of HtrA1 and the T2 value was
      analyzed. RESULTS The T2 value of the nucleus pulposus region was 33.11-167.91
      ms, with an average of 86.64+/-38.73 ms. According to Spearman correlation
      analysis, there was a rank correlation between T2 value and Pfirrmann grade
      (P<0.0001), and the correlation coefficient (rs)=-0.93617. There was a linear
      correlation between the mRNA level of HtrA1 and T2 value in nucleus pulposus
      tissues (a=3.88, b=-0.019, F=112.63, P<0.0001), normalized regression
      coefficient=-0.88. There was a linear correlation between the expression level of
      HtrA1 protein and the T2 value in the nucleus pulposus tissues (a=3.30, b=-0.016,
      F=93.15, P<0.0001) and normalized regression coefficient=-0.86. CONCLUSIONS The
      expression of HtrA1 was strongly related to the T2 value, suggesting that HtrA1
      plays an important role in the pathological process of intervertebral disc
      degeneration.

PMID- 28432853
TI  - An Evidence-Based Approach to Reducing Cardiac Telemetry Alarm Fatigue.
AB  - BACKGROUND: It is estimated that between 80% and 99% of alarms in the clinical
      areas are in actionable alarms (Gross, Dahl, & Nielson). Alarm management is one
      of the Joint Commission's National Patient Safety Goals (2014) because sentinel
      events have directly been linked to the devices generating these alarms. PURPOSE:
      At an acute care facility in Boston, a multidisciplinary team consisting of
      Nursing, Biomedical Engineers, Patient Safety and Providers was formed to conduct
      a pilot study on the state of telemetry alarms on a surgical floor. METHODS: An
      evidence-based approach was taken utilizing Philips Real-time data exporter
      alarms tracking software to capture all telemetry alarms during a 43-day time
      span. Likewise, noise meters were placed near telemetry alarm speakers to track
      decibel levels within the aforementioned timeframe for 21 days. Analysis of the
      data showed that clinically insignificant Premature Ventricular Contractions
      (PVC) alarms accounted for more than 40% of all alarms in the unit within the
      time span, while also contributing to an average noise level of 58.49 dB. In
      response to the data, the interdisciplinary team approved to permanently default
      the settings for PAIR PVC, MULTIFORM PVC, and RUN PVC alarms to off. RESULTS: The
      results showed a 54% decrease in the rate of alarms per bed per day, and an
      average noise reduction of 2.3 dB between the two selected noise measurement
      areas. LINKING EVIDENCE TO ACTION: Organizing a multidisciplinary team provides
      an effective framework toward analyzing and addressing cardiac telemetry alarm
      fatigue. Looking at quantitative datasets for clinical care areas through various
      lenses helps identify opportunities for improvement in regards to highlighting
      alarms that are not actionable. Pilot changes to alarm parameters can be tested
      for their environmental impact in the care area.

PMID- 28432854
TI  - Quality of death, rumination, and posttraumatic growth among bereaved family
      members of cancer patients in home palliative care.
AB  - OBJECTIVE: The current study was designed to test the hypothesis that quality of
      death (QOD) and intrusive and deliberate rumination are associated with
      posttraumatic growth (PTG) among bereaved family members of cancer patients in
      home palliative care. METHODS: Data were collected from 805 bereaved family
      members of cancer patients who died at home in Japan. We used a cross-sectional
      design and participants completed Good Death Inventory, Event-Related Rumination
      Inventory, and PTG Inventory. Structural equation modeling was used to test the
      hypothesized relationships. RESULTS: A direct pathway from QOD to PTG was
      significant. We also found significant indirect pathways between QOD and PTG via
      deliberate rumination soon after the death and recent deliberate rumination.
      CONCLUSIONS: Clinicians should provide high-quality end-of-life care with the
      goals of achieving a good death for terminally ill cancer patients and supporting
      the experience of PTG in bereaved family members after their loss.

PMID- 28432855
TI  - A systematic review of psychotherapeutic interventions for women with metastatic
      breast cancer: Context matters.
AB  - OBJECTIVES: To summarise the evidence-base of psychological interventions for
      women with metastatic breast cancer, by mode of delivery (group, individual, or
      low-intensity interventions). To synthesise data regarding core intervention
      elements (eg, intervention duration) and context factors (trial setting, uptake
      and adherence, and demographic characteristics). METHODS: Four databases were
      searched (inception-May 2016): MEDLINE (OvidSP), PsycINFO (OvidSP), CINAHL
      (EBSCO), and SCOPUS; reference lists were examined for additional publications.
      Grey literature was excluded. Outcome data were extracted for survival, distress,
      quality of life, coping, sleep, fatigue, and/or pain and summarised through
      narrative synthesis. RESULTS: Fifteen randomised clinical trials (RCTs), reported
      across 23 articles, met inclusion criteria: 7 groups, 4 individuals, and 4 low
      intensity interventions. Overall, interventions improved distress (8/13 RCTs),
      coping (4/5 RCTs), and pain (4/5 RCTs). No evidence of survival benefit was
      found. For remaining outcomes, evidence was either insufficient, or too mixed to
      draw conclusions. Group programs had the strongest evidence-base for efficacy;
      individual and low-intensity therapy had insufficient evidence to form
      conclusions. Group interventions had longest intervention durations and lowest
      uptake and adherence; low-intensity interventions had shortest durations and
      highest uptake and adherence. Disparities in uptake, adherence, and reach were
      evident, with the demographic profile of participants polarised to young,
      Caucasian, English-speaking, partnered women. CONCLUSIONS: There remains a
      paucity of psychological interventions for women with metastatic breast cancer.
      Those that exist have an inconsistent evidence-base across the range of patient
      reported outcomes. Further research is needed to evaluate accessible delivery
      formats that ensure efficacy as well as uptake.

PMID- 28432856
TI  - The Effectiveness of Exercise in Adults With Systemic Lupus Erythematosus: A
      Systematic Review and Meta-Analysis to Guide Evidence-Based Practice.
AB  - BACKGROUND: Fatigue is the most common and unpleasant symptom of patients with
      systemic lupus erythematosus (SLE). However, there is limited information
      regarding how exercise affects fatigue. AIMS: The purpose of this study is to
      review and synthesize the current knowledge concerning the effectiveness of
      exercise training for treating fatigue among adults with SLE. The characteristics
      of beneficial exercise training are further evaluated. METHODS: We conducted a
      systematic review and meta-analysis. The databases searched were MEDLINE, CINAHL,
      PEDro, Cochrane Library, Scopus, and PQDT from their inception to February 3,
      2016. The quality of each selected study was assessed using the PEDro scale. A
      between-group analysis was performed to evaluate the effectiveness of the
      exercise training. Data were analyzed using the Cochrane Collaboration's RevMan
      5.3 (Copenhagen, Denmark). RESULTS: Two randomized controlled trials and one
      quasiexperimental study were included in this systematic review and meta
      analysis. Aerobic exercise, three times a week and of moderate intensity, was a
      common component of the three studies. Two studies were conducted in a supervised
      setting and one study was based at home. One study lasted 8 weeks and two studies
      lasted 12 weeks. The meta-analysis showed that aerobic exercise could decrease
      fatigue (MD = -.52, 95% confidence interval [CI] [-.91, -.13], p = .009) and
      increase vitality (MD = 14.98, 95% CI [7.45, 22.52], p < .001). The subgroup
      analysis indicated that 12 weeks of exercise training and exercise under a
      supervised setting significantly benefited fatigue. LINKING EVIDENCE TO ACTION:
      The pooled data indicate that 12 weeks of an aerobic exercise program that is
      supervised by health professionals could reduce fatigue and increase vitality for
      patients with SLE. SLE patients with mild disease should begin with moderate
      intensity for at least 20 minutes, 3 days a week.

PMID- 28432857
TI  - On the importance of intramolecular hydrogen bond cooperativity in d-glucose - an
      NMR and QTAIM approach.
AB  - The idea that hydrogen bond cooperativity is responsible for the structure and
      reactivity of carbohydrates is examined. Density functional theory and gauge
      including atomic orbital calculations on the known conformers of the alpha and
      beta anomers of d-glucopyranose in the gas phase are used to compute proton NMR
      chemical shifts and interatomic distances, which are taken as criteria for
      probing intramolecular interactions. Atom-atom interaction energies are
      calculated by the interacting quantum atoms approach in the framework of the
      quantum theory of atoms in molecules. Association of OH1 in the counterclockwise
      conformers with a strong acceptor, pyridine, is accompanied by cooperative
      participation from OH2, but there is no significant change in the bonding of the
      two following 1,2-diol motifs. The OH6... O5 (G-g+/cc/t and G+g-/cc/t conformers)
      or OH6... O4 (Tg+/cc/t conformer) distance is reduced, and the OH6 proton is
      slightly deshielded. In the latter case, this shortening and the associated
      increase in the OH6-O4 interaction energy may be interpreted as a small
      cooperative effect, but intermolecular interaction energies are practically the
      same for all three conformers. In most of the pyridine complexes, one ortho
      proton interacts with the endocyclic oxygen O5. Analogous results are obtained
      when the clockwise conformer, G-g+/cl/g-, detected for the alpha anomer, and a
      hypothetical conformer, Tt/cl/g-, are complexed with pyridine through OH6.
      Generally, the cooperative effect does not go beyond the first two OH groups of a
      chain. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28432858
TI  - Regulatory function of parasites in autoimmune disease - outcome from
      experimental model infection
AB  - It is estimated that more than half of the nowadays known species are pathogenic
      parasites. Among macroparasites gastrointestinal nematodes are one of most common
      and having significant impact on life and health. Those organisms reveal strong,
      specific immune response in host, involving primary mechanisms associated with
      regulatory and Th2 cells. Referring to immunomodulatory abilities of helminths,
      parasite infections started to be considered as a possible therapy for many
      autoimmune diseases. Clinical trials on 2nd and 3rd stage are conducted in spite
      that treatment has not been recognized as safe for common use. Despite that the
      safety of treatment with parasites is still controversial and widely discussed.
      Our knowledge about mechanisms used by helminth to moderate immune response is
      still inadequate to predict possible effect of long lasting parasite infection on
      individual patients.

PMID- 28432859
TI  - The impact of global climate change on the spread of parasitic nematodes
AB  - Climate changes may influence the frequency, intensity and geographical
      distribution of parasites, directly affecting their dispersive stages in the
      environment (eggs, larvae) and, indirectly, the larvae living mainly in
      invertebrate intermediate hosts. In biologically diverse nematodes climate
      warming contributes to the increase in the range of distribution, colonization of
      new hosts and modification of their development cycles. This is particularly
      acute in the Arctic and pertains, for instance, to nematodes Ostertagia gruehneri
      and Setaria tundra parasitizing reindeer Rangifer tarandus and Umingmakstrongylus
      pallikuukensis in musk oxen (Ovibos moschatus). Increase in range expansion of
      mosquitoes Culicidae caused that nematodes of the genus Dirofilaria, especially
      D. repens, have beenlisted in autochthonous invasions even in the northern and
      eastern European countries. In addition, extended range of occurrence is also
      shown by Ancylostoma braziliense - a parasite of carnivores in the tropical and
      subtropical countries. In recent years over 20 cases of autochthonous creeping
      eruption (CE) caused by cutanea larva migrans (CLM) A. braziliense were detected
      in people in southern Europe (Italy, Spain, France, Germany).

PMID- 28432860
TI  - High Ki-67 expression is associated with prolactin secreting pituitary adenomas.
AB  - Pituitary adenomas represent the third most common primary intracranial tumor in
      neurosurgical practice. To understand the biological behaviour of the pituitary
      adenomas previous studies have determined the tumor proliferation rate using
      monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study
      was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas.
      The study included 50 pituitary adenomas. For histopathologic evaluation, the
      sections were stained with routine hematoxylin and eosin method. Additional
      paraffin sections from each tumor were immunostained using primary antibodies
      against the following pituitary hormones: somatotropin (STH), prolactin (PRL),
      adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle
      stimulating hormone (FSH), and luteinizing hormone (LH). To detect the expression
      of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The
      percentage of Ki-67 positive nuclei (Ki-67 labeling index) was assessed by
      counting approximately 1000 nuclei of the tumor cells at *400 magnification. Out
      of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative
      activity, and the proliferation rate was variable in this group. The overall mean
      Ki-67 labeling index was 1.59 +/- 1.47, ranging from 0.3% to 6.6%. In 5 cases,
      the Ki-67 index was >3%, all of them being prolactinomas. The Ki-67 index was
      higher in PRL-secreting adenomas (mean +/- SD was 3.37 +/- 1.80, range 0.9 -
      6.6%). Our study provides the evidence that a higher Ki-67 value is associated
      with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL
      secreting adenomas).

PMID- 28432861
TI  - Spirometry and volumetric capnography in lung function assessment of obese and
      normal-weight individuals without asthma.
AB  - OBJECTIVE: To analyze and compare lung function of obese and healthy, normal
      weight children and adolescents, without asthma, through spirometry and
      volumetric capnography. METHODS: Cross-sectional study including 77 subjects (38
      obese) aged 5-17 years. All subjects underwent spirometry and volumetric
      capnography. The evaluations were repeated in obese subjects after the use of a
      bronchodilator. RESULTS: At the spirometry assessment, obese individuals, when
      compared with the control group, showed lower values of forced expiratory volume
      in the first second by forced vital capacity (FEV1/FVC) and expiratory flows at
      75% and between 25 and 75% of the FVC (p<0.05). Volumetric capnography showed
      that obese individuals had a higher volume of produced carbon dioxide and
      alveolar tidal volume (p<0.05). Additionally, the associations between dead space
      volume and tidal volume, as well as phase-3 slope normalized by tidal volume,
      were lower in healthy subjects (p<0.05). These data suggest that obesity does not
      alter ventilation homogeneity, but flow homogeneity. After subdividing the groups
      by age, a greater difference in lung function was observed in obese and healthy
      individuals aged >11 years (p<0.05). CONCLUSION: Even without the diagnosis of
      asthma by clinical criteria and without response to bronchodilator use, obese
      individuals showed lower FEV1/FVC values and forced expiratory flow, indicating
      the presence of an obstructive process. Volumetric capnography showed that obese
      individuals had higher alveolar tidal volume, with no alterations in ventilation
      homogeneity, suggesting flow alterations, without affecting lung volumes.

PMID- 28432862
TI  - A closer look at the fetal programming hypothesis with obstetric ultrasound.

PMID- 28432863
TI  - Prevalence and factors associated with breast milk donation in banks that receive
      human milk in primary health care units.
AB  - OBJECTIVE: To estimate the prevalence and to analyze factors associated with
      breast milk donation at primary health care units in order to increase the human
      milk bank reserves. METHODS: Cross-sectional study carried out in 2013 in Rio de
      Janeiro, Brazil. A representative sample of 695 mothers of children younger than
      1 year attended to at the nine primary health care units with human milk donation
      services were interviewed. A hierarchical approach was used to obtain adjusted
      prevalence ratios (APR) by Poisson regression with robust variance. The final
      model included the variables associated with breast milk donation (p<=0.05).
      RESULTS: 7.3% of the mothers had donated breast milk. Having been encouraged to
      donate breast milk by healthcare professionals, relatives, or friends (APR=7.06),
      receiving information on breast milk expression by the primary health care unit
      (APR=3.65), and receiving help from the unit professionals to breastfeed
      (APR=2.24) were associated with a higher prevalence of donation. Admission of the
      newborn to the neonatal unit was associated with a lower prevalence of donation
      (APR=0.09). CONCLUSIONS: Encouragement to breast milk donation, and information
      and help provided by primary health care unit professionals to breastfeeding were
      shown to be important for the practice of human milk donation.

PMID- 28432864
TI  - Plutonium in the atmosphere: A global perspective.
AB  - A number of potential source terms have contributed plutonium isotopes to the
      atmosphere. The atmospheric nuclear weapon tests conducted between 1945 and 1980
      and the re-entry of the burned SNAP-9A satellite in 1964, respectively. It is
      generally believed that current levels of plutonium in the stratosphere are
      negligible and compared with the levels generally found at surface-level air. In
      this study, the time trend analysis and long-term behavior of plutonium isotopes
      (239+240Pu and 238Pu) in the atmosphere were assessed using historical data
      collected by various national and international monitoring networks since 1960s.
      An analysis of historical data indicates that 239+240Pu concentration post-1984
      is still frequently detectable, whereas 238Pu is detected infrequently.
      Furthermore, the seasonal and time-trend variation of plutonium concentration in
      surface air followed the stratospheric trends until the early 1980s. After the
      last Chinese test of 1980, the plutonium concentrations in surface air dropped to
      the current levels, suggesting that the observed concentrations post-1984 have
      not been under stratospheric control, but rather reflect the environmental
      processes such as resuspension. Recent plutonium atmospheric air concentrations
      data show that besides resuspension, other environmental processes such as global
      dust storms and biomass burning/wildfire also play an important role in
      redistributing plutonium in the atmosphere.

PMID- 28432865
TI  - Assessment of radiological efficiency of countermeasures on peat-bog soils of
      Ukrainian Polissya.
AB  - In the field conditions, the long-term (2013-2015) small-plots experiment was
      carried out for evaluation of radiological efficiency of application of
      ameliorants as the countermeasures for reduction of the 137Cs uptake to herbage
      at the Peat-boggy (Histosols) soils of Ukrainian Polissya. At the late stage
      after the Chernobyl accident, the average radiological efficiencies of
      application of sand (175-200 ton ha-1) and ferrocyn (0.2 ton ha-1) as the
      ameliorants were rather low ranging from 0.8 to 1.6. Application of 4 ton ha-1 of
      chalk and 5 ton ha-1 of peat ash decreased 1.7-1.9 times the 137Cs activity
      concentrations in plans. The highest radiological efficiencies, 4.4 +/- 2.0 and 7
      +/- 2, were reached at applications of chalk-ferrocyn ameliorant (4 + 0.2 ton ha
      1) and ferrocyn-bentonite absorbent HZH-90 (30 ton ha-1), respectively.

PMID- 28432867
TI  - Examining the direct and indirect effects of visual-verbal paired associate
      learning on Chinese word reading.
AB  - Associative learning, traditionally measured with paired associate learning (PAL)
      tasks, has been found to predict reading ability in several languages. However,
      it remains unclear whether it also predicts word reading in Chinese, which is
      known for its ambiguous print-sound correspondences, and whether its effects are
      direct or indirect through the effects of other reading-related skills such as
      phonological awareness and rapid naming. Thus, the purpose of this study was to
      examine the direct and indirect effects of visual-verbal PAL on word reading in
      an unselected sample of Chinese children followed from the second to the third
      kindergarten year. A sample of 141 second-year kindergarten children (71 girls
      and 70 boys; mean age=58.99months, SD=3.17) were followed for a year and were
      assessed at both times on measures of visual-verbal PAL, rapid naming, and
      phonological awareness. In the third kindergarten year, they were also assessed
      on word reading. The results of path analysis showed that visual-verbal PAL
      exerted a significant direct effect on word reading that was independent of the
      effects of phonological awareness and rapid naming. However, it also exerted
      significant indirect effects through phonological awareness. Taken together,
      these findings suggest that variations in cross-modal associative learning (as
      measured by visual-verbal PAL) place constraints on the development of word
      recognition skills irrespective of the characteristics of the orthography
      children are learning to read.

PMID- 28432866
TI  - Shared genetic influences among childhood shyness, social competences, and
      cortical responses to emotions.
AB  - Visual event-related potentials (ERPs) evoked by facial expressions are useful to
      map socioemotional responses among shy children and to predict transition into
      social phobia. We investigated the sources of covariation among childhood
      shyness, social competences, and ERPs to other children's happy, neutral, and
      angry expressions. Electrophysiological and twin analyses examined the phenotypic
      and etiological association among an index of childhood shyness, an index of
      social competences, and ERP responses to facial expressions in 200 twins (mean
      age=9.23years). Multivariate twin analyses showed that the covariation among
      shyness, social competences, and a composite of a frontal late negative component
      occurring around 200-400ms in response to happy, neutral, and angry expressions
      could be entirely explained by shared genetic factors. A coherent causal
      structure links childhood shyness, social competences, and the cortical responses
      to facial emotions. A common genetic substrate can explain the interrelatedness
      of individual differences for childhood shyness, social competences, and some
      associated electrophysiological responses to socioemotional signals.

PMID- 28432869
TI  - Editorial Comment.

PMID- 28432868
TI  - Reply by Authors.

PMID- 28432870
TI  - This Month in AJP.

PMID- 28432871
TI  - miR-24-3p Is Overexpressed in Hodgkin Lymphoma and Protects Hodgkin and Reed
      Sternberg Cells from Apoptosis.
AB  - miRNAs play important roles in biological processes, such as proliferation,
      metabolism, differentiation, and apoptosis, whereas altered expression levels
      contribute to diseases, such as cancers. We identified miRNAs with aberrant
      expression in Hodgkin lymphoma (HL) and investigated their role in pathogenesis.
      Small RNA sequencing revealed 84 significantly differentially expressed miRNAs in
      HL cell lines as compared to germinal center B cells. Three up-regulated miRNAs
      miR-23a-3p, miR-24-3p, and miR-27a-3p-were derived from one primary miRNA
      transcript. Loss-of-function analyses for these miRNAs and their seed family
      members resulted in decreased growth on miR-24-3p inhibition in three HL cell
      lines and of miR-27a/b-3p inhibition in one HL cell line. Apoptosis analysis
      indicated that the effect of miR-24-3p on cell growth is at least in part caused
      by an increase of apoptotic cells. Argonaute 2 immunoprecipitation revealed 1142
      genes consistently targeted by miRNAs in at least three of four HL cell lines.
      Furthermore, 52 of the 1142 genes were predicted targets of miR-24-3p. Functional
      annotation analysis revealed a function related to cell growth, cell death,
      and/or apoptosis for 15 of the 52 genes. Western blotting of the top five genes
      showed increased protein levels on miR-24-3p inhibition for CDKN1B/P27kip1 and
      MYC. In summary, we showed that miR-24-3p is up-regulated in HL and its
      inhibition impairs cell growth possibly via targeting CDKN1B/P27kip1 and MYC.

PMID- 28432872
TI  - Human Effector Memory T Helper Cells Engage with Mouse Macrophages and Cause
      Graft-versus-Host-Like Pathology in Skin of Humanized Mice Used in a Nonclinical
      Immunization Study.
AB  - Humanized mice engrafted with human hematopoietic stem cells and developing
      functional human T-cell adaptive responses are in critical demand to test human
      specific therapeutics. We previously showed that humanized mice immunized with
      long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65)
      exhibited a faster development and maturation of T cells. Herein, we evaluated
      these effects in a long-term (36 weeks) nonclinical model using two stem cell
      donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization
      boosted the output of effector memory CD4+ T cells in peripheral blood and lymph
      nodes. No weight loss, human malignancies, or systemic graft-versus-host (GVH)
      disease were observed. However, for one reconstitution cohort, some mice
      immunized with iDCpp65 showed GVH-like signs on the skin. Histopathology analyses
      of the inflamed skin revealed intrafollicular and perifollicular human CD4+ cells
      near F4/80+ mouse macrophages around hair follicles. In spleen, CD4+ cells formed
      large clusters surrounded by mouse macrophages. In plasma, high levels of human T
      helper 2-type inflammatory cytokines were detectable, which activated in vitro
      the STAT5 pathway of murine macrophages. Despite this inflammatory pattern, human
      CD8+ T cells from mice with GVH reacted against the pp65 antigen in vitro. These
      results uncover a dynamic cross-species interaction between human memory T cells
      and mouse macrophages in the skin and lymphatic tissues of humanized mice.

PMID- 28432873
TI  - Conditional Deletion of Bmal1 Accentuates Microvascular and Macrovascular Injury.
AB  - The brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein
      (BMAL)-1 constitutes a major transcriptional regulator of the circadian clock.
      Here, we explored the impact of conditional deletion of Bmal1 in endothelium and
      hematopoietic cells in murine models of microvascular and macrovascular injury.
      We used two models of Bmal1fx/fx;Tek-Cre mice, a retinal ischemia/reperfusion
      model and a neointimal hyperplasia model of the femoral artery. Eyes were
      enumerated for acellular capillaries and were stained for oxidative damage
      markers using nitrotyrosine immunohistochemistry. LSK (lineage-negative, stem
      cell antigen-1-positive, c-Kit-positive) cells were quantified and proliferation
      assessed. Hematopoiesis is influenced by innervation to the bone marrow, which we
      assessed using IHC analysis. The number of acellular capillaries increased
      threefold, and nitrotyrosine staining increased 1.5-fold, in the retinas of
      Bmal1fx/fx;Tek-Cre mice. The number of LSK cells from the Bmal1fx/fx;Tek-Cre mice
      decreased by 1.5-fold and was accompanied by a profound decrease in proliferative
      potential. Bmal1fx/fx;Tek-Cre mice also exhibited evidence of bone marrow
      denervation, demonstrating a loss of neurofilament-200 staining. Injured femoral
      arteries showed a 20% increase in neointimal hyperplasia compared with similarly
      injured wild-type controls. Our study highlights the importance of the circadian
      clock in maintaining vascular homeostasis and demonstrates that specific deletion
      of BMAL1 in endothelial and hematopoietic cells results in phenotypic features
      similar to those of diabetes.

PMID- 28432875
TI  - One-Step Surgical Correction of Transverse and Anteroposterior Maxillary
      Deficiencies Using Wire Fixation. A New Approach and Long-Term Stability.
AB  - PURPOSE: To describe a retrospective assessment of the long-term stability of a
      new approach using wire fixation for 1-step surgical correction of transverse and
      anteroposterior maxillary deficiencies. PATIENTS AND METHODS: The authors
      implemented a case series of 5 adult patients (3 men and 2 women; mean age, 31.4
      yr) needing maxillary advancement less than 5 mm and had transverse maxillary
      deficiency greater than 7 mm who underwent total Le Fort I and median palatal
      suture osteotomies and had their maxilla advanced and stabilized bilaterally with
      stainless steel wire. Transverse expansion was performed using a Hyrax expander,
      which also was used for retention for 4 months after completion of the planned
      expansion. Follow-up included clinical examination and studies of lateral
      radiographs and plaster models preoperatively (T0), soon after completion of
      maxillary expansion (T1), 4 months after T1 (T2), 12 months after T1 (T3), and an
      average of 4.8 years (minimum, 4 yr 1 month; maximum, 5 yr; standard deviation,
      0.3 yr) after T1 (T4). RESULTS: Maxillary expansions measured at the most
      cervical points on the palatal face of the upper first premolars and of the upper
      first molars at T2 were 7.8 and 7.4 mm on average, respectively. In all cases,
      surgery promoted maxillary anteroposterior advancement. Anteroposterior maxillary
      skeletal measurements of the angle formed by the sella, nasion, and A point; the
      distance from the vertical reference line to the A point (A-VRL); the distance of
      the VRL to the cementoenamel junction (CEJ); and the distance from the
      perpendicular line of the nasion (Nperp) to the CEJ showed a substantially
      increase at T1 (P < .05) and stability at T2, T3, and T4; however, A-VRL
      presented a significant relapse at T4 compared with T1 (P = .037) and T2 (P =
      .027). The soft tissues expanded at the same rate as the skeletal tissues. The
      anteroposterior soft tissue measurements Nperp to superior lip and Nperp to the
      A' point showed a substantial increase at T2 (P < .05) and stability at T3 and
      T4. The measurements associated with anteroposterior correction were stable at
      T4. CONCLUSION: The proposed technique provides long-term stability of maxillary
      expansion and anteroposterior repositioning with only 1 surgical intervention.
      However, considering the small number of patients, a multicenter study is needed
      before a definitive conclusion can be reached.

PMID- 28432874
TI  - Delayed changes in auditory status in cochlear implant users with preserved
      acoustic hearing.
AB  - This retrospective review explores delayed-onset hearing loss in 85 individuals
      receiving cochlear implants designed to preserve acoustic hearing at the
      University of Iowa Hospitals and Clinics between 2001 and 2015. Repeated measures
      of unaided behavioral audiometric thresholds, electrode impedance, and
      electrically evoked compound action potential (ECAP) amplitude growth functions
      were used to characterize longitudinal changes in auditory status. Participants
      were grouped into two primary categories according to changes in unaided
      behavioral thresholds: (1) stable hearing or symmetrical hearing loss and (2)
      delayed loss of hearing in the implanted ear. Thirty-eight percent of this sample
      presented with delayed-onset hearing loss of various degrees and rates of change.
      Neither array type nor insertion approach (round window or cochleostomy) had a
      significant effect on prevalence. Electrode impedance increased abruptly for many
      individuals exhibiting precipitous hearing loss; the increase was often
      transient. The impedance increases were significantly larger than the impedance
      changes observed for individuals with stable or symmetrical hearing loss.
      Moreover, the impedance changes were associated with changes in behavioral
      thresholds for individuals with a precipitous drop in behavioral thresholds.
      These findings suggest a change in the electrode environment coincident with the
      change in auditory status. Changes in ECAP thresholds, growth function slopes,
      and suprathreshold amplitudes were not correlated with changes in behavioral
      thresholds, suggesting that neural responsiveness in the region excited by the
      implant is relatively stable. Further exploration into etiology of delayed-onset
      hearing loss post implantation is needed, with particular interest in mechanisms
      associated with changes in the intracochlear environment.

PMID- 28432876
TI  - Effect of pistachio consumption on the modulation of urinary gut microbiota
      related metabolites in prediabetic subjects.
AB  - The specific nutritional composition of nuts could affect different metabolic
      pathways involved in a broad range of metabolic diseases. We therefore
      investigated whether chronic consumption of pistachio nuts modifies the urine
      metabolome in prediabetic subjects. We designed a randomized crossover clinical
      trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet
      (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a
      control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2
      week wash-out. Nuclear magnetic resonance (NRM) was performed to determine
      changes in 24-h urine metabolites. Significant changes in urine metabolites
      according to the different intervention periods were found in uni- and
      multivariate analysis. Score plot of the first two components of the multilevel
      partial least squares discriminant analysis (ML-PLS-DA) showed a clear separation
      of the intervention periods. Three metabolites related with gut microbiota
      metabolism (i.e., hippurate, p-cresol sulfate and dimethylamine) were found
      decreased in PD compared with CD (P<.05). Moreover, cis-aconitate [intermediate
      of the tricarboxylic acid (TCA)] was also found decreased following PD compared
      with CD. Intragroup analysis showed that creatinine levels were significantly
      increased in PD (P=.023), whereas trimethylamine N-oxide (TMAO) was found
      significantly reduced following PD (P=.034). Our results suggest that chronic
      pistachio consumption may modulate some urinary metabolites related to gut
      microbiota metabolism and the TCA cycle; all associated with metabolic
      derangements associated with insulin resistance and Type 2 diabetes.

PMID- 28432878
TI  - In vitro susceptibility of methicillin-resistant Staphylococcus aureus isolates
      from skin and soft tissue infections to vancomycin, daptomycin, linezolid and
      tedizolid.
AB  - INTRODUCTION: Treatment of multidrug-resistant Gram-positive infections caused by
      Staphylococcus aureus remains as a clinical challenge due to emergence of new
      resistance mechanisms. Tedizolid is a next-generation oxazolidinone, recently
      approved for skin and soft tissues infections. We conducted a study to determine
      in vitro susceptibility to vancomycin, daptomycin, linezolid and tedizolid in
      MRSA clinical isolates from adult patients with skin and soft tissue infections.
      MATERIAL AND METHODS: Methicillin-resistant S. aureus isolates were collected in
      three tertiary-care hospitals of Medellin, Colombia, from February 2008 to June
      2010 as part of a previous study. Clinical characteristics were assessed by
      medical records and MIC values were determined by Epsilometer test. Genotypic
      analysis included spa typing, MLST, and SCCmec typing. RESULTS: A total of 150
      MRSA isolates were evaluated and tedizolid MIC values obtained showed higher in
      vitro activity than other antimicrobials, with MIC values ranging from 0.13MUg/mL
      to 0.75MUg/mL and lower values of MIC50 and MIC90 (0.38MUg/mL and 0.5MUg/mL). In
      contrast, vancomycin and linezolid had higher MIC values, which ranged from
      0.5MUg/mL to 2.0MUg/mL and from 0.38MUg/mL to 4.0MUg/mL, respectively. Tedizolid
      MICs were 2- to 5-fold lower than those of linezolid. Clinical characteristics
      showed high previous antimicrobial use and hospitalization history. The majority
      of the strains belong to the CC8 harboring the SCCmec IVc and were associated
      with the spa t1610 (29.33%, n=44). CONCLUSION: In vitro effectiveness of
      tedizolid was superior for isolates from skin and soft tissue infections in
      comparison with the other antibiotics evaluated. The above added to its less
      toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment,
      make tedizolid in a promising alternative for the treatment of infections caused
      by MRSA.

PMID- 28432879
TI  - Seasonal variation and health risk assessment of organochlorine compounds in
      urban soils of Novi Sad, Serbia.
AB  - The aim of this paper was to determine spatial and seasonal variation of 6
      indicator polychlorinated biphenyls (PCBs) and 18 organochlorine pesticides
      (OCPs) in urban soils of Novi Sad, Serbia. Sixty surface soil samples were
      collected during both winter and summer season, from different types of
      locations: schools, recreational areas, residential and industrial zones. Samples
      were treated using the method of accelerated solvent extraction, which allows
      simultaneous extraction and clean up of PCBs and OCPs. Targeted compounds were
      analyzed by GC-MUECD and confirmed by GC-MS. The total concentrations of studied
      PCBs varied from <LOD to 18.9 ng g-1 (mean 2.84 ng g-1 and median value of 1.21
      ng g-1) in winter and from <LOD to 24.6 ng g-1 (mean 3.27 ng g-1 and median value
      of 1.60 ng g-1) in summer. Regarding the OCPs analyzed,
      dichlorodiphenyltrichloroethanes (DDTs) were only detected in both seasons. The
      total concentration of DDTs ranging from <LOD to 86.3 ng g-1 (mean 7.57 ng g-1
      and median value of 1.87 ng g-1) in summer and from <LOD to 182 ng g-1 (mean 15.6
      ng g-1 and median value of 3.15 ng g-1) in winter. There were no significant
      difference between seasons for studied PCBs and DDTs. Spatial distribution of
      PCBs and DDTs were also evaluated using Arc GIS. Additional, principle component
      analysis was performed to evaluate relationships between PCBs, DDTs and soil
      characteristics. Positive correlation was observed among p,p'-DDE, p,p'-DDD and
      organic matter. The total lifetime carcinogenic risk indicated that the lifetime
      cancer risk was acceptable.

PMID- 28432877
TI  - Maternal low-protein diet decreases brain-derived neurotrophic factor expression
      in the brains of the neonatal rat offspring.
AB  - Prenatal exposure to a maternal low-protein (LP) diet has been known to cause
      cognitive impairment, learning and memory deficits. However, the underlying
      mechanisms have not been identified. Herein, we demonstrate that a maternal LP
      diet causes, in the brains of the neonatal rat offspring, an attenuation in the
      basal expression of the brain-derived neurotrophic factor (BDNF), a neurotrophin
      indispensable for learning and memory. Female rats were fed either a 20% normal
      protein (NP) diet or an 8% LP 3 weeks before breeding and during the gestation
      period. Maternal LP diet caused a significant reduction in the Bdnf expression in
      the brains of the neonatal rats. We further found that the maternal LP diet
      reduced the activation of the cAMP/protein kinase A/cAMP response element binding
      protein (CREB) signaling pathway. This reduction was associated with a
      significant decrease in CREB binding to the Bdnf promoters. We also show that
      prenatal exposure to the maternal LP diet results in an inactive or repressed
      exon I and exon IV promoter of the Bdnf gene in the brain, as evidenced by fluxes
      in signatory hallmarks in the enrichment of acetylated and trimethylated histones
      in the nucleosomes that envelop the exon I and exon IV promoters, causing the
      Bdnf gene to be refractory to transactivation. Our study is the first to
      determine the impact of a maternal LP diet on the basal expression of BDNF in the
      brains of the neonatal rats exposed prenatally to an LP diet.

PMID- 28432880
TI  - Immobilization of Cu, Zn, Cd and Pb in mine drainage stream sediment using
      Chinese loess.
AB  - The in situ immobilization of metal-contaminated sediment, using various
      amendments, has attracted great attention owing to their cost-effectiveness. The
      present study investigated the effectiveness of Chinese loess on Cu, Zn, Cd and
      Pb stabilization by decreasing their bioavailability in contaminated sediment.
      The loess was mixed with the sediment in doses of 0, 0.5, 1, 2, 5, 10 and 20 kg.
      Approximately 70 d after loess application, the effectiveness was evaluated using
      the Tessier sequential extraction procedure and single extractants, including
      ethylenediaminetetraacetic acid disodium salt (EDTA-2Na),
      diethylenetriaminepentaacetic acid (DTPA), calcium chloride (CaCl2) and
      hydrochloric acid (HCl). The results indicated that the loess can effectively
      transform Cu from the carbonate fraction into the residual fraction when the
      loess dose was >=5 kg. However, loess had little effect on Zn, Cd and Pb
      immobilization. Correlation analysis showed that these four extractants can
      provide a good indication of the toxicity of Cu, Zn, Cd and Pb in the amended
      sediment. Additionally, the organic matter content in the amended sediment
      decreased by 1.4% for CK, 1.6% for L0.5, 1.7% for L1, 1.5% for L2, 1.5% for L5,
      1.9% for L10 and 1.9% for L20 (CK: untreated sediment; L0.5 to L20 represent
      loess doses of 0.5, 1, 2, 5, 10 and 20 kg, respectively) compared to the initial
      organic matter content in the unamended sediment, which may increase the
      atmospheric carbon dioxide owing to the degradation of organic matter.

PMID- 28432881
TI  - Improvement in cadmium tolerance of edible rape (Brassica rapa L.) with exogenous
      application of chitooligosaccharide.
AB  - Cadmium (Cd) is one of the most toxic heavy metals, which is readily taken up by
      plant roots and has deleterious effects on crop yield and quality. The study
      investigated the potential cross-protection roles of chitooligosaccharide (COS)
      in alleviating Cd toxicity in edible rape (Brassica rapa L.) under greenhouse
      conditions. The results demonstrated that spraying COS onto the leaves of edible
      rape could promote the plant growth and leaf chlorophyll contents, decrease the
      malondialdehyde (MDA) level in leaves as well as the Cd2+ concentration in shoots
      and roots of edible rape under Cd stress. Moreover, exogenous COS could obviously
      enhance the activities of superoxide dismutase (SOD), catalase (CAT) and
      peroxidase (POX) in edible rape leaves under Cd-toxicity. The alleviation effect
      of COS on Cd stress was concentration-dependent and COS of 50-100 mg L-1 showed
      the best activity. Subcellular distribution experiments further revealed that COS
      of 50 mg L-1 decreased the proportion of Cd in the organelle fraction of leaves
      by 40.1% while increased the proportion of Cd in the soluble fraction by 13.2%.
      These results indicated that COS had a potential to enhance plant resistance to
      Cd through promoting antioxidant enzyme activities and altering Cd subcellular
      distribution.

PMID- 28432882
TI  - Analysis of factors affecting the severity of crashes in urban road
      intersections.
AB  - Road crashes are events which depend on a variety of factors and which exhibit
      different magnitudes of outputs when evaluated with respect to the effects on
      road users. Despite a lot of research into the evaluation of crash likelihood and
      frequency, only a few works have focused exclusively on crash severity with these
      limited to sections of freeways and multilane highways. Hence, at present there
      is a large gap in knowledge on factors affecting the severity of crashes for
      other road categories, facilities, and scenarios. The paper deals with the
      identification of factors affecting crash severity level at urban road
      intersections. Two official crash records together with a weather database, a
      traffic data source with data aggregated into 5min intervals, and further
      information characterising the investigated urban intersections were used.
      Analyses were performed by using a back propagation neural network model and a
      generalized linear mixed model that enable the impact assessment of flow and
      other variables. Both methods demonstrate that flows play a role in the
      prediction of severity levels.

PMID- 28432883
TI  - Sagittal plane joint kinetics during stair ascent in patients with peripheral
      arterial disease and intermittent claudication.
AB  - Stair negotiation poses a substantial physical demand on the musculoskeletal
      system and this challenging task can place individuals at risk of falls.
      Peripheral arterial disease (PAD) can cause intermittent claudication (IC) pain
      in the calf and results in altered gait mechanics during level walking. However,
      whether those with PAD-IC adopt alternate strategies to climb stairs is unknown.
      Twelve participants with PAD-IC (six bilateral and six unilateral) and 10 healthy
      controls were recruited and instructed to ascend a five-step staircase whilst 3D
      kinematic data of the lower-limbs were recorded synchronously with kinetic data
      from force plates embedded into the staircase on steps two and three. Limbs from
      the unilateral group and both limbs from the bilateral claudicants were
      categorised as claudicating (N=18), asymptomatic (N=6) and control (N=10).
      Claudicants walked more slowly than healthy controls (trend; P=<0.066). Both
      claudicating- and asymptomatic-limb groups had reduced propulsive GRF (P=0.025
      and P=0.002, respectively) and vertical GRF (P=0.005 and P=0.001, respectively)
      compared to controls. The claudicating-limb group had a reduced knee extensor
      moment during forward continuance (P=0.060), ankle angular velocity at peak
      moment (P=0.039) and ankle power generation (P=0.055) compared to the controls.
      The slower gait speed, irrespective of laterality of symptoms, indicates
      functional capacity was determined by the limitations of the claudicating limb.
      Reduced ankle power generation and angular velocity (despite adequate
      plantarflexor moment) implies velocity-dependent limitations existed in the calf.
      The lack of notable compensatory strategies indicates reliance on an impaired
      muscle group to accomplish this potentially hazardous task, highlighting the
      importance of maintaining plantarflexor strength and power in those with PAD-IC.

PMID- 28432884
TI  - Use of presepsin and procalcitonin for prediction of SeptiFast results in
      critically ill patients.
AB  - PURPOSE: There is a need for identification of marker that could lead physicians
      to take the right step towards laboratory techniques for documentation of
      infection. The aim of this study was to investigate whether presepsin and
      procalcitonin (PCT) levels in patients with suspected sepsis could predict blood
      culture (BC) and SeptiFast (SF) results. MATERIAL AND METHODS: 100 patients were
      included in our study. PCT, C-reactive protein (CRP), and presepsin levels were
      determined. Differences between groups of patients were assessed by Mann-Whitney
      U test. Categorical variables were compared using chi-square test. Receiver
      operating characteristic (ROC) curves were plotted to determine predictive values
      of biomarkers for prediction of positive SF results. RESULTS: PCT (70.9+/-106.36
      vs. 16.35+/-26.79) and presepsin (4899.73+/-5207.81 vs. 1751.59+/-2830.62) were
      significantly higher in patients with positive SF in contrast to patients with
      negative SF. There was no significant difference between patients who had
      positive and negative BC for PCT and presepsin values. PCT and presepsin showed a
      similar performance in predicting positive SF results with AUC of 0.75 for PCT
      and 0.73 for presepsin. CONCLUSION: Presepsin can serve as good predictor of
      bacteremia detected by SF and it should be included with PCT in protocols for
      sepsis diagnosing.

PMID- 28432885
TI  - From laboratory to field studies - The assessment of Biscutella laevigata
      suitability to biological reclamation of areas contaminated with lead and
      cadmium.
AB  - The aim of the work was to evaluate the usefulness of the in vitro multiplication
      of Biscutella laevigata calamine ecotype for in situ reclamation of post
      flotation wastes polluted with Pb and Cd. The experiment was conducted on three
      steps: (i) plant shoots' production under in vitro condition, (ii) establishment
      of the material in greenhouse experiment, and finally (iii) field cultivation
      directly on the mining-waste heap of Olkusz Ore-Bearing Region, Poland. This
      region is known to be one of the most chemically-degraded area in central Europe.
      The laboratory-set in vitro analysis enabled to obtain the high-quality plant
      shoots, which multiply the most effectively (with growth tolerance index 130
      150%) on medium containing 5.0MUM CdCl2 and 0.5mM Pb(NO3)2. These plants were
      used for the next two ex vitro experiments. Several biometric and physiological
      analysis (i.e. of photosystem II activity Fv/Fm and PI, photosynthetic pigment
      contents) were done to indicate plant physiological status during these
      experiments. The main novelty of the work was to prove that in vitro-multiplied
      shoots of B. laevigata - the representative of native flora from Olkusz Ore
      Bearing Region - can be successfully implemented in situ for the restoration of
      these degraded area. Moreover, the addition of sewage sludge as a source of
      organic compounds significantly improved plants' growth and development what is
      especially important due to the lack of other legal solutions for the management
      of the sewage sludge in some countries.

PMID- 28432886
TI  - Evaluation of biochar-ultrafiltration membrane processes for humic acid removal
      under various hydrodynamic, pH, ionic strength, and pressure conditions.
AB  - The performance of an ultrafiltration (UF)-biochar process was evaluated in
      comparison with a UF membrane process for the removal of humic acid (HA). Bench
      scale UF experiments were conducted to study the rejection and flux trends under
      various hydrodynamic, pH, ionic strength, and pressure conditions. The resistance
      in-series model was used to evaluate the processes and it showed that unlike
      stirred conditions, where low fouling resistance was observed (28.7 * 1012 m-1 to
      32.5 * 1012 m-1), higher values and comparable trends were obtained for UF
      biochar and UF alone for unstirred conditions (28.7 * 1012 m-1 to 32.5 * 1012 m
      1). Thus, the processes were further evaluated under unstirred conditions.
      Additionally, total fouling resistance was decreased in the presence of biochar
      by 6%, indicating that HA adsorption by biochar could diminish adsorption fouling
      on the UF membrane and thus improve the efficiency of the UF-biochar process. The
      rejection trends of UF-biochar and UF alone were similar in most cases, whereas
      UF-biochar showed a noticeable increase in flux of around 18-25% under various
      experimental conditions due to reduced membrane fouling. Three-cycle filtration
      tests further demonstrated that UF-biochar showed better membrane recovery and
      antifouling capability by showing more HA rejection (3-5%) than UF membrane alone
      with each subsequent cycle of filtration. As a result of these findings, the UF
      biochar process may potentially prove be a viable treatment option for the
      removal of HA from water.

PMID- 28432887
TI  - Application of a gammaRS index-based method and techno-economic analysis for in
      situ treatment of 137Cs-contaminated soils by cement-barite based
      stabilisation/solidification.
AB  - This paper examines the application of cement (C)-barite (Ba) based
      Stabilisation/Solidification (S/S) for the remediation of 137Cs-contaminated
      soils, investigating the influence of soil: grout and C: Ba ratios on the
      shielding performance of the S/S mix assessed as gamma radiation shielding
      (gammaRS) index variation. Results from experiments were used to perform a novel
      approach and an economic analysis in order to calculate the effective dose
      reduction achievable by S/S and to assess the optimum quantities and costs of
      selected mixes, respectively. Gamma ray spectrometer measurements indicate that
      gammaRS index increases with increasing barite percentage up to a maximum level
      of 50%; however a further increase results in a worsening of the shielding
      performances. A maximum gammaRS variation of 46.5% was recorded with grout
      percentage increasing from 16.6 to 50%. At the photon energy of 662 keV (137Cs),
      the maximum grout amount results in the possibility to shield up to 24.1% of
      gamma-rays emitted. The effective dose reduction achievable by the investigated
      S/S allows a maximum 137Cs-soil contamination in the range 2.94-14.55 kBq kg-1
      successfully treatable employing a soil: grout ratio of 1: 1 (C: Ba = 1:1).
      Technical data, jointly with economic analysis findings, make cement-barite based
      S/S very competitive in cost-effectiveness and could provide a basis for decision
      making of 137Cs-contaminated site remediation.

PMID- 28432888
TI  - Removal of arsenate and dichromate ions from different aqueous media by amine
      based p(TAEA-co-GDE) microgels.
AB  - In this work, microgels based on tris(2-aminoethyl) amine (TAEA) and glycerol
      diglycidyl ether (GDE) via simple microemulsion polymerization was prepared as
      p(TAEA-co-GDE) microgels were used as adsorbent for removal of dichromate (Cr
      (VI)) and arsenate (As (V)) ions from different aqueous environments. The p(TAEA
      co-GDE) microgels were demonstrated very efficient adsorption capacity for Cr
      (VI), and As (V) that are 164.98 mg/g, and 123.64 mg/g from distilled (DI) water,
      respectively. The effect of the medium pH on the adsorption capacity of p(TAEA-co
      GDE) microgels for Cr (VI) and As (V) ions were investigated. The maximum
      adsorption capacity was obtained at pH 4.0 for both ions with maximum adsorbed
      amounts of 160.62, and 98.72 mg/g, respectively. In addition, the microgels were
      also shown moderate adsorption capacity for Cr (VI) and As (V) from other water
      sources; tap water with 115.18 mg/g and 82.86 mg/g, sea water with 64.24 mg/g and
      46.88 mg/g and creek water with 73.52 mg/g and 59.33 mg/g, respectively.
      Moreover, the increase in adsorbent dose from 0.025 to 0.125 g enhanced %
      adsorption of Cr (VI) from 54.13 to 98.03, and As (V) from % 26.72-98.70,
      respectively. For the adsorption process Langmuir and Freundlich adsorption
      isotherms were applied and found that Langmuir adsorption isotherm with R2 value
      of 0.99 for both the metal ions are suitable. Moreover, the experimental
      adsorption capacities of Cr (VI) and As (V) were found very close to the
      theoretical values calculated from Langmuir adsorption isotherm. More
      importantly, the microgels were made magnetic responsive to recover them easily
      from adsorption medium for reuse studies by applying external magnetic field with
      little decrease in adsorption capacity. Additionally, reusability of p(TAEA-co
      GDE) microgels was also evaluated for adsorption of Cr (VI) and As (V) from DI
      water.

PMID- 28432889
TI  - Reducing domestic heating demand: Managing the impact of behavior-changing
      feedback devices via marketing.
AB  - Feedback devices can be used to inform households about their energy-consumption
      behavior. This may persuade them to practice energy conservation. The use of
      feedback devices can also-via word of mouth-spread among households and thereby
      support the spread of the incentivized behavior, e.g. energy-efficient heating
      behavior. This study investigates how to manage the impact of these environmental
      innovations via marketing. Marketing activities can support the diffusion of
      devices. This study aims to identify the most effective strategies of marketing
      feedback devices. We did this by adapting an agent-based model to simulate the
      roll-out of a novel feedback technology and heating behavior within households in
      a virtual city. The most promising marketing strategies were simulated and their
      impacts were analyzed. We found it particularly effective to lend out feedback
      devices to consumers, followed by leveraging the social influence of well
      connected individuals, and giving away the first few feedback devices for free.
      Making households aware of the possibility of purchasing feedback devices was
      found to be least effective. However, making households aware proved to be most
      cost-efficient. This study shows that actively managing the roll-out of feedback
      devices can increase their impacts on energy-conservation both effectively and
      cost-efficiently.

PMID- 28432890
TI  - Characterization of spectral responses of dissolved organic matter (DOM) for
      atrazine binding during the sorption process onto black soil.
AB  - This study was aim to investigate the interaction between soil-derived dissolved
      organic matter (DOM) and atrazine as a kind of pesticides during the sorption
      process onto black soil. According to the experimental data, the adsorption
      capacity of Soil + DOM, Soil and DOM were 41.80, 31.45 and 9.35 mg kg-1,
      separately, which indicated that DOM significantly enhanced the adsorption
      efficiency of atrazine by soil. Data implied that the pseudo-second-order kinetic
      equation could well explain the adsorption process. The adsorption isotherms (R2
      > 0.99) had a satisfactory fit in both Langmuir and Freundlich models. Three
      dimensional excitation-emission matrix (3D-EEM), synchronous fluorescence, two
      dimensional correlation spectroscopy (2D-COS) and Fourier transform infrared
      spectroscopy (FT-IR) were selected to analyze the interaction between DOM and
      atrazine. 3D-EEM showed that humic acid-like substances were the main component
      of DOM. The fluorescence of DOM samples were gradually quenched with the
      increased of atrazine concentrations. Synchronous fluorescence spectra showed
      that static fluorescence quenching was the main quenching process. 2D-COS
      indicated that the order of the spectral changes were as following: 336 nm > 282
      nm. Furthermore, the fluorescence quenching of humic-like fraction occurred
      earlier than that of protein-like fraction under atrazine surroundings. FT-IR
      spectra indicated that main compositions of soil DOM include proteins,
      polysaccharides and humic substances. The findings of this study are significant
      to reveal DOM played an important role in the environmental fate of pesticides
      during sorption process onto black soil and also provide more useful information
      for understanding the interaction between DOM and pesticides by using spectral
      responses.

PMID- 28432891
TI  - Modification of an existing in vitro method to predict relative bioavailable
      arsenic in soils.
AB  - The soil matrix can sequester arsenic (As) and reduces its exposure by soil
      ingestion. In vivo dosing studies and in vitro gastrointestinal (IVG) methods
      have been used to predict relative bioavailable (RBA) As. Originally, the Ohio
      State University (OSU-IVG) method predicted RBA As for soils exclusively from
      mining and smelting sites with a median of 5,636 mg As kg-1. The objectives of
      the current study were to (i) evaluate the ability of the OSU-IVG method to
      predict RBA As for As contaminated soils with a wider range of As content and As
      contaminant sources, and (ii) evaluate a modified extraction procedure's ability
      to improve prediction of RBA As. In vitro bioaccessible (IVBA) by OSU-IVG and
      California Bioaccessibility Method (CAB) methods, RBA As, speciation, and
      properties of 33 As contaminated soils were determined. Total As ranged from 162
      to 12,483 mg kg-1 with a median of 73 mg kg-1. RBA As ranged from 1.30 to 60.0%
      and OSU-IVG IVBA As ranged from 0.80 to 52.3%. Arsenic speciation was
      predominantly As(V) adsorbed to hydrous ferric oxide (HFO) or iron (Fe),
      manganese (Mn), and aluminum (Al) oxides. The OSU-IVG often extracted
      significantly less As in vitro than in vivo RBA As, in particularly for soils
      from historical gold mining. The CAB method, which is a modified OSU-IVG method
      extracted more As than OSU-IVG for most soils, resulting in a more accurate
      predictor than OSU-IVG, especially for low to moderately contaminated soils
      (<1,500 mg As kg-1) with RBA As = 0.81 IVBA As + 3.2, r2 = 0.91.

PMID- 28432892
TI  - Arsenic, chromium, molybdenum, and selenium: Geochemical fractions and potential
      mobilization in riverine soil profiles originating from Germany and Egypt.
AB  - The fractionation and potential mobilization of As, Cr, Mo, and Se in four
      floodplain soil profiles collected along the Nile (Egypt) and Wupper (Germany)
      Rivers were assessed using the BCR sequential extraction procedure. The
      concentrations of total and the geochemical fractions (acid soluble (F1),
      reducible (F2), oxidizable (F3), and residual (F4) fraction) of the elements were
      determined. The Wupper soils had the highest total concentrations (mg kg-1) of As
      (378) and Cr (2,797) while the Nile soils contained the highest total Mo (12) and
      Se (42). The residual fraction of As, Cr, Mo, and Se was dominant in the Nile
      soils suggesting the geogenic source of the elements in these soils. The residual
      fraction of As and Mo and the oxidizable fraction of Cr and Se were dominant in
      the Wupper soils. Among the non-residual fractions (potential mobile fractions;
      PMF = ?F1-F3), the oxidizable fraction was dominant for Cr, Mo, and Se in the
      Nile soils and for Mo in the Wupper soils, while the reducible fraction was
      dominant for As in both soils. The PMF of As, Cr, and Se was higher in the Wupper
      than in the Nile soils which might reflect the anthropogenic sources of these
      elements in the Wupper soils, while the opposite was the case for the PMF of Mo.
      The high PMF of Se (87%), Cr (87%), and As (21%) in the Wupper soils suggested
      that a release of these toxic elements may happen which increase the potential
      environmental risks in the anthropogenically polluted soils.

PMID- 28432893
TI  - Optimism and benefit finding in parents of children with developmental
      disabilities: The role of positive reappraisal and social support.
AB  - BACKGROUND: Researchers have consistently documented the relationship between
      optimism and benefit finding; however, there is a dearth of research on the
      psychological mechanisms mediating their association. AIM: This cross-sectional
      study sought to elucidate the mediating role of positive reappraisal and social
      support in the optimism-benefit finding relationship in parents caring for
      children with developmental disabilities by testing a parallel multiple mediation
      model. METHOD: One hundred and forty-six parents caring for children with
      developmental disabilities completed an online survey assessing optimism,
      positive reappraisal, social support and benefit finding. RESULTS: Optimism was
      not directly related to benefit finding but rather influenced it indirectly
      through positive reappraisal and social support. Specifically, higher levels of
      optimism predicted greater positive reappraisal and social support, which in turn
      led to greater benefit finding in parents. CONCLUSION: These results underscore
      the importance of targeting parents' perceptions of benefits through both
      positive reappraisal and social support in order to help them cope with the
      demands of the caregiving context.

PMID- 28432894
TI  - The structure, correlates, and treatment related changes of mindfulness facets
      across the anxiety disorders and obsessive compulsive disorder.
AB  - Research with non-clinical and clinical samples has examined how mindfulness
      concepts relate to psychological symptom presentations. However, there is less
      clarity when examining treatment-seeking patients who experience DSM-diagnosed
      anxiety and obsessional disorders - both cross-sectionally, and following
      empirically-supported treatments. The Five Facet Mindfulness Questionnaire (FFMQ;
      Baer, Smith, Hopkins, Krietemeyer, & Toney, 2006) conceptualizes mindfulness as
      consisting of five facets: Observing, Describing, Acting with Awareness,
      Nonreactivity, and Nonjudging. The current study examines the factor structure
      and predictive validity of the FFMQ in a large sample of treatment-seeking
      individuals with obsessive compulsive disorder (OCD), panic disorder with or
      without agoraphobia (PD/A), social anxiety disorder (SAD), and generalized
      anxiety disorder (GAD). Confirmatory factor analyses (CFA) established that both
      four and five-factor models (i.e., with and without inclusion of the Observing
      factor) provided an acceptable representation of the underlying FFMQ structure,
      but did not support a one-factor solution. For each of these diagnostic groups,
      hierarchical regression analyses clarified the association between specific FFMQ
      facets and diagnosis specific symptom change during CBT treatment. These findings
      are discussed in the context of the possible transdiagnostic relevance of
      specific mindfulness facets, and how these facets are differentially associated
      with diagnosis specific symptom alleviation during CBT.

PMID- 28432895
TI  - Predictive ability of visit-to-visit variability in HbA1c and systolic blood
      pressure for the development of microalbuminuria and retinopathy in people with
      type 2 diabetes.
AB  - AIMS: We explored whether visit-to-visit variability in both glycated hemoglobin
      (HbA1c) and systolic blood pressure (SBP) simultaneously predicted the
      development of microalbuminuria and retinopathy, and whether the predictive
      ability of these measurements changed according to mean HbA1c and SBP levels in
      people with type 2 diabetes. METHODS: A retrospective observational cohort study
      was conducted on 243 type 2 diabetes patients with normoalbuminuria and 486
      without retinopathy at the first visit and within 1year thereafter. The two
      cohorts were followed up from 1995 until 2012. Multivariate and stratified
      analyses were performed using Cox proportional hazard models. RESULTS:
      Microalbuminuria developed in 84 patients and retinopathy in 108. Hazard ratios
      (HRs) for the development of microalbuminuria associated with the coefficient of
      variation (CV) and variation independent of mean (VIM) of both HbA1c and SBP
      significantly increased. In participants with a mean SBP <130mmHg, the HRs for
      the development of retinopathy associated with CV and VIM of HbA1c were abruptly
      elevated and significant compared with those with a mean SBP >=130mmHg.
      CONCLUSIONS: Visit-to-visit variability in both HbA1c and SBP simultaneously
      predict the development of microalbuminuria. HbA1c variability may predict the
      development of retinopathy when the mean SBP is normal (<130mmHg).

PMID- 28432896
TI  - Diabetes incidence and influencing factors in women with and without gestational
      diabetes mellitus: A 15year population-based follow-up cohort study.
AB  - AIM: Very few extensive follow-up investigations evaluating patients with history
      of gestational diabetes mellitus (GDM) have been documented. We conducted this
      longitudinal study to estimate the incidence of diabetes and its predictors in
      women with and without GDM. METHOD: A total of 2458 eligible women, aged 20
      50years (476 with GDM and 1982 without GDM) were selected from among participants
      of the Tehran Lipid and Glucose study, based on the World Health Organization
      definition for GDM screening. Pooled logistic regression was used to assess the
      association between time-dependent covariates and diabetes. RESULTS: The
      incidence rate of diagnosed diabetes was 9/1000 for women with GDM and 4/1000 for
      their counterparts, without GDM. Kaplan-Meier curve indicated a significantly
      shorter median time for developing diabetes in women with a history of GDM
      (6.95years [IQ: 4.22-10.71]), compared to their healthy peers (8.45years [IQ:
      5.08-10.89]). BMI and previous family history of diabetes were found as major
      risk factors for future diabetes in women with GDM. CONCLUSION: The results
      presented here lead to better identification and selection of at-risk women with
      prior GDM history.

PMID- 28432897
TI  - HbA1c variability in type 2 diabetes is associated with the occurrence of new
      onset albuminuria within three years.
AB  - AIMS: To evaluate the association between HbA1c coefficient of variation (HbA1c
      CV) and 3-year new-onset albuminuria risk. METHODS: A retrospective cohort study
      involving 716 normoalbuminuric type 2 diabetes patients was conducted between
      2010 and 2014. HbA1c-CV was used to categorize patients into low, moderate or
      high variability groups. Multivariate logistic models were constructed and
      validated. Integrated discrimination (IDI) and net reclassification (NRI)
      improvement indices were used to quantify the added predictive value of HbA1c-CV.
      RESULTS: The mean age of our cohort was 56.1+/-12.9years with a baseline HbA1c of
      8.3+/-1.3%. Over 3-years of follow-up, 35.2% (n=252) developed albuminuria. An
      incremental risk of albuminuria was observed with moderate (6.68-13.43%) and high
      (above 13.44%) HbA1c-CV categories demonstrating adjusted odds ratios of 1.63
      (1.12-2.38) and 3.80 (2.10-6.97) for 3-year new-onset albuminuria, respectively.
      Including HbA1c-CV for 3-year new-onset albuminuria prediction improved model
      discrimination (IDI: 0.023, NRI: 0.293, p<0.05). The final model had a C
      statistic of 0.760+/-0.018 on validation. CONCLUSION: HbA1c-CV improves 3-year
      prediction of new-onset albuminuria. Together with mean HbA1c, baseline urine
      albumin-to-creatinine ratio and presence of hypertension, accurate 3-year new
      onset albuminuria prediction may be possible.

PMID- 28432898
TI  - Cost-effectiveness of sensor-augmented pump therapy versus standard insulin pump
      therapy in patients with type 1 diabetes in Denmark.
AB  - AIMS: The use of continuous subcutaneous insulin infusion (CSII) in type 1
      diabetes (T1D) has increased in recent years. Sensor-augmented pump therapy (SAP)
      with low glucose suspend (LGS) (allowing temporary suspension of insulin delivery
      if blood glucose level falls below a pre-defined threshold level) provides
      additional benefits over CSII alone, but is associated with higher acquisition
      costs. Therefore, a cost-effectiveness analysis of SAP+LGS versus CSII in
      patients with T1D was performed. METHODS: Analyses were performed using the CORE
      Diabetes Model in two different patient cohorts in Denmark, one with
      hyperglycemia at baseline and one with increased risk for hypoglycemic events.
      Clinical input data were sourced from published literature. The analysis was
      performed over a lifetime time horizon from a societal perspective. Future costs
      and clinical outcomes were discounted at 3% per annum. RESULTS: In patients who
      were hyperglycemic at baseline the use of SAP+LGS versus CSII resulted in
      improved quality-adjusted life expectancy (12.44 versus 10.99 quality-adjusted
      life years [QALYs]) but higher mean lifetime costs (DKK 2,027,316 versus DKK
      1,801,293) leading to an incremental cost-effectiveness ratio (ICER) of DKK
      156,082 per QALY gained. For patients at increased risk for hypoglycemic events
      the ICER for SAP+LGS versus CSII was DKK 89,868 per QALY gained. CONCLUSIONS: The
      ICER for SAP+LGS versus CSII falls below commonly cited willingness-to-pay
      thresholds. Therefore, in Denmark, the use of SAP+LGS is likely to be considered
      cost-effective relative to CSII for patients with T1D who are either
      hyperglycemic, despite CSII use, or who experience frequent severe hypoglycemic
      events.

PMID- 28432899
TI  - Serum MicroRNAs Related with Chemoradiotherapy Resistance in Advanced-Stage
      Cervical Squamous Cell Carcinoma.
AB  - OBJECTIVE: To investigate the serum microRNAs as biomarkers in predicting
      chemoradiotherapy resistance in advanced-stage cervical squamous cell carcinoma
      (ACSCC) patients. METHODS: Serum samples were collected from International
      Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB cervical
      squamous cell carcinoma patients treated with platinum based Concomitant
      Chemoradiotherapy (CCRT) in our hospital during September 2013 to November 2015.
      Twenty well-matched samples (10 resistant and 10 sensitive) were chosen to screen
      the miRNA expression profile using serum samples pooled with microarrays. miRNAs
      expressed significantly different between two groups were further verified in 131
      patients (29 resistant and 102 sensitive) serum samples with TaqMan Real-time
      PCR. The AUC was used to evaluate the accuracy of the biomarkers for prediction.
      RESULTS: MiR-136-5, miR-152-3p and miR-206 were expressed significantly different
      between sensitive and resistant groups. Results of 131 patients verification
      showed that the levels of miR-206 in sensitive samples and resistant samples were
      2.715+/-0.2115 and 14.64+/-1.184, respectively, which was significantly different
      (P<.0001), while miR-136-5p and miR-152-3p could not be tested without pre
      amplification reactions. Univariate analysis revealed that miR-206 expression was
      significantly associated with patients' DFS. Multivariate analysis demonstrated
      that miR-206 expression, tumor differentiation and pelvic lymph nodes metastasis
      were the independent prognostic factors associated with DFS in this cohort
      (P=.008, 0.000, 0.000, respectively). The probability of the prognostic accuracy
      of miR-206 expression in predicting chemoradiotherapy sensitivity of ACSCC
      patients was 91.3% (79.3% sensitivity and 92.2% specificity). CONCLUSION: Serum
      miR-206 is a powerful tool in predicting chemoradiotherapy sensitivity in ACSCC
      patients.

PMID- 28432900
TI  - Lysophosphatidic acid induces expression of genes in human oral keratinocytes
      involved in wound healing.
AB  - OBJECTIVE: Epithelial cells participate in wound healing by covering wounds, but
      also as important mediators of wound healing processes. Topical application of
      the phospholipid growth factor lysophosphatidic acid (LPA) accelerates dermal
      wound healing and we hypothesized that LPA can play a role in human oral wound
      healing through its effects on human oral keratinocytes (HOK). DESIGN: HOK were
      isolated from gingival biopsies and exposed to LPA. The LPA receptor profile,
      signal transduction pathways, gene expression and secretion of selected cytokines
      were analyzed. RESULTS: HOK expressed the receptors LPA1, LPA5 and LPA6 and LPA
      activated the ERK1/2, JNK and p38 intracellular pathways, substantiated by
      secretion of IL-6 and IL-8. The early (2h) and intermediate (6h) gene expression
      profiles of HOK after LPA treatment showed a wide array of regulated genes. The
      majority of the strongest upregulated genes were related to chemotaxis and
      inflammation, and became downregulated after 6h. At 6h, genes coding for factors
      involved in extracellular matrix remodeling and re-epithelialization became
      highly expressed. IL-36gamma, not earlier known to be regulated by LPA, was
      strongly transcribed and translated but not secreted. CONCLUSIONS: After
      stimulation with LPA, HOK responded by regulating factors and genes that are
      essential in wound healing processes. As LPA is found in saliva and is released
      by activated cells after wounding, our results indicate that LPA has a favorable
      physiological role in oral wound healing. This may further point towards a
      beneficial role for application of LPA on oral surgical or chronic wounds.

PMID- 28432901
TI  - Neuromuscular rate of force development deficit in Parkinson disease.
AB  - BACKGROUND: Bradykinesia and reduced neuromuscular force exist in Parkinson
      disease. The interpolated twitch technique has been used to evaluate central
      versus peripheral manifestations of neuromuscular strength in healthy, aging, and
      athletic populations, as well as moderate to advanced Parkinson disease, but this
      method has not been used in mild Parkinson disease. This study aimed to evaluate
      quadriceps femoris rate of force development and quantify potential central and
      peripheral activation deficits in individuals with Parkinson disease. METHODS:
      Nine persons with mild Parkinson Disease (Hoehn & Yahr<=2, Unified Parkinson
      Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched
      controls were recruited in a cross-sectional investigation. Quadriceps femoris
      voluntary and stimulated maximal force and rate of force development were
      evaluated using the interpolated twitch technique. FINDINGS: Thirteen
      participants satisfactorily completed the protocol. Individuals with early
      Parkinson disease (n=7) had significantly slower voluntary rate of force
      development (p=0.008; d=1.97) and rate of force development ratio (p=0.004;
      d=2.18) than controls (n=6). No significant differences were found between groups
      for all other variables. INTERPRETATIONS: Persons with mild-to-moderate Parkinson
      disease display disparities in rate of force development, even without deficits
      in maximal force. The inability to produce force at a rate comparable to controls
      is likely a downstream effect of central dysfunction of the motor pathway in
      Parkinson disease.

PMID- 28432902
TI  - Ayahuasca's entwined efficacy: An ethnographic study of ritual healing from
      'addiction'.
AB  - BACKGROUND: A range of studies has demonstrated the efficacy of the psychoactive
      Amazonian brew ayahuasca in addressing substance addiction. These have revealed
      that physiological and psychological mechanisms are deeply enmeshed. This article
      focuses on how interactive ritual contexts support the healing effort. The study
      of psychedelic-assisted treatments for addiction has much to gain from
      ethnographic analyses of healing experiences within the particular ecologies of
      use and care, where these interventions are rendered efficacious. METHODS: This
      is an ethnographically grounded, qualitative analysis of addiction-recovery
      experiences within ayahuasca rituals. It draws on long-term fieldwork and
      participant observation in ayahuasca communities, and in-depth, semi-structured
      interviews of participants with histories of substance misuse. RESULTS:
      Ayahuasca's efficacy in the treatment of addiction blends somatic, symbolic and
      collective dimensions. The layering of these effects, and the direction given to
      them through ritual, circumscribes the experience and provides tools to render it
      meaningful. Prevailing modes of evaluation are ill suited to account for the
      particular material and semiotic efficacy of complex interventions such as
      ayahuasca healing for addiction. The article argues that practices of care
      characteristic of the ritual spaces in which ayahuasca is collectively consumed,
      play a key therapeutic role. CONCLUSION: The ritual use of ayahuasca stands in
      strong contrast to hegemonic understandings of addiction, paving new ground
      between the overstated difference between community and pharmacological
      interventions. The article concludes that fluid, adaptable forms of caregiving
      play a key role in the success of addiction recovery and that feeling part of a
      community has an important therapeutic potential.

PMID- 28432904
TI  - Optimising multi-frame ADF-STEM for high-precision atomic-resolution strain
      mapping.
AB  - Annular dark-field scanning transmission electron microscopy is a powerful tool
      to study crystal defects at the atomic scale but historically single slow-scanned
      frames have been plagued by low-frequency scanning-distortions prohibiting
      accurate strain mapping at atomic resolution. Recently, multi-frame acquisition
      approaches combined with post-processing have demonstrated significant
      improvements in strain precision, but the optimum number of frames to record has
      not been explored. Here we use a non-rigid image registration procedure before
      applying established strain mapping methods. We determine how, for a fixed total
      electron-budget, the available dose should be fractionated for maximum strain
      mapping precision. We find that reductions in scanning-artefacts of more than 70%
      are achievable with image series of 20-30 frames in length. For our setup, series
      longer than 30 frames showed little further improvement. As an application, the
      strain field around an aluminium alloy precipitate was studied, from which our
      optimised approach yields data whos strain accuracy is verified using density
      functional theory.

PMID- 28432903
TI  - The decidua of preeclamptic-like BPH/5 mice exhibits an exaggerated inflammatory
      response during early pregnancy.
AB  - Preeclampsia is a devastating complication of pregnancy characterized by late
      gestation hypertension and proteinuria. Because the only definitive treatment is
      delivery of the fetus and placenta, preeclampsia contributes to increased
      morbidity and mortality of both mother and fetus. The BPH/5 mouse model, which
      spontaneously develops a syndrome strikingly similar to preeclampsia, displays
      excessive inflammation and suppression of inflammation improves pregnancy
      outcomes. During early pregnancy, decidual macrophages play an important role in
      promoting maternal tolerance to fetal antigens and regulating tissue remodeling,
      two functions that are critical for normal placental development. BPH/5
      pregnancies are characterized by abnormal placentation; therefore, we
      hypothesized that macrophage localization and/or function is altered during early
      pregnancy at the site of placental formation (the decidua) compared to C57BL/6
      controls. At early gestation time points, before the onset of maternal
      hypertension or proteinuria, there was a reduction in the number of macrophages
      in BPH/5 decidua and a concomitant increase in activated T cells compared with
      C57BL/6. BPH/5 decidua also exhibited decreased expression of the
      immunosuppressive cytokine, IL-10, and increased expression of pro-inflammatory,
      inducible nitric oxide synthase. Together, these data suggest that a reduction in
      decidual macrophages during pregnancy is associated with immune activation in
      BPH/5 mice, inadequate placental development and may contribute to adverse
      pregnancy outcomes in this model.

PMID- 28432905
TI  - Statistical analysis of dislocations and dislocation boundaries from EBSD data.
AB  - Electron BackScatter Diffraction (EBSD) is often used for semi-quantitative
      analysis of dislocations in metals. In general, disorientation is used to assess
      Geometrically Necessary Dislocations (GNDs) densities. In the present paper, we
      demonstrate that the use of disorientation can lead to inaccurate results. For
      example, using the disorientation leads to different GND density in
      recrystallized grains which cannot be physically justified. The use of
      disorientation gradients allows accounting for measurement noise and leads to
      more accurate results. Misorientation gradient is then used to analyze
      dislocations boundaries following the same principle applied on TEM data before.
      In previous papers, dislocations boundaries were defined as Geometrically
      Necessary Boundaries (GNBs) and Incidental Dislocation Boundaries (IDBs). It has
      been demonstrated in the past, through transmission electron microscopy data,
      that the probability density distribution of the disorientation of IDBs and GNBs
      can be described with a linear combination of two Rayleigh functions. Such
      function can also describe the probability density of disorientation gradient
      obtained through EBSD data as reported in this paper. This opens the route for
      determining IDBs and GNBs probability density distribution functions separately
      from EBSD data, with an increased statistical relevance as compared to TEM data.
      The method is applied on deformed Tantalum where grains exhibit dislocation
      boundaries, as observed using electron channeling contrast imaging.

PMID- 28432906
TI  - Hydrophobic and hydrophilic properties of pollutants as a factor influencing
      their redistribution during snowpack melt.
AB  - Glaciers accumulate organic pollutants delivered by snow. However, our
      understanding of the exact dynamics of organic pollutants in the snowpack relies
      primarily on laboratory experiments and mathematical models. To fill the gap
      related to the detailed field data, we have conducted observations of melting
      snow profiles in two locations and three different stages of melting on one High
      Arctic glacier, as well as in superimposed ice. We monitored the chemical
      concentrations of formaldehyde, phenols, short-chain carboxylic acids, polycyclic
      aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) and snow water
      equivalents to derive chemical loads. The obtained organic contaminant
      redistribution patterns are compared to the meltwater removal model by Meyer and
      Wania (2011), in order to link the behaviour of chemicals to their hydrophilic or
      hydrophobic properties. Both the later snowpits and the superimposed ice layer
      were generally more abundant in particulate organics and hydrophobic compounds,
      despite the initial prevalence of hydrophilic organic chemicals. The chemical
      species with high water solubility also showed less predictable elution patterns,
      due to their chemical reactivity and possible photochemical reactions in the
      snowpack. Finally, ice layers in the snowpack showed very different chemical
      characteristics to the underlying superimposed ice, so one cannot be used as a
      chemical proxy for another. In order to interpret the ice core records correctly,
      the temporal changes in concentration of different pollutant types should be
      considered, as glaciers may preferentially accumulate hydrophobic organics that
      tarry in the snow cover.

PMID- 28432907
TI  - Assessment of field re-entry exposure to pesticides: A dislodgeable foliar
      residue study.
AB  - A dislodgeable foliar residue study was conducted in greenhouse pepper and tomato
      on the island of Crete, Greece, following the spray application of an SC
      insecticide (with active substance (a.s.) tebufenozide) and an EC fungicide (a.s.
      bupirimate). Furthermore, for the assessment of worker exposure to pesticides -
      as a result of re-entering the treated crops - a worker dermal exposure study was
      carried out during the tasks of tying or pruning, which allowed the transfer
      coefficient values for the specific tasks to be determined. Pesticide residues
      were analysed with an in house developed and fully validated HPLC-ESI/MS
      analytical method. The results from the study resulted in transfer coefficient
      values which were in agreement with current EFSA guideline values in most of the
      cases with the exception of bupirimate in a tomato greenhouse. In that case, high
      potential dermal exposure and low dislodgeable foliar residue values were
      observed, which is thought to be due to the moist leaves collected during
      sampling and monitoring, which led to greater than expected transfer coefficient
      values.

PMID- 28432908
TI  - Particulate matter pollution from aviation-related activity at a small airport of
      the Aegean Sea Insular Region.
AB  - The unprecedented growth in aviation during the last years has resulted in a
      notable increase of local air pollution related to airports. The impacts of
      aviation on air quality can be extremely high particularly around airports
      serving remote insular regions with pristine atmospheric environments. Here we
      report measurements that show how the atmospheric aerosol is affected by the
      activity at a small airport in a remote region. More specifically, we provide
      measurements performed at the airport of Mytilene, Greece, a regional yet
      international airport that serves the entire island of Lesvos; the third largest
      island of the country. The measurements show that the activity during landing,
      taxiing and take-off of the aircrafts accounted for up to a 10-fold increase in
      particulate matter (PM) mass concentration in the vicinity of the airport. The
      number concentration of particles having diameters from 10 to 500nm also
      increased from ca. 4*102 to 8*105particlescm-3, while the mean particle diameter
      decreased to 20nm when aircrafts were present at the airport. Elemental analysis
      on particle samples collected simultaneously at the airport and at a remote site
      3km away, showed that the former were significantly influenced by combustion
      sources, and specifically from the engines of the aircrafts. Our results show
      that despite their small size, local airports serving remote insular regions
      should be considered as important air pollution hotspots, raising concerns for
      the exposure of the people working and leaving in their vicinities to hazardous
      pollutants.

PMID- 28432909
TI  - Source-receptor relationships for PM2.5 during typical pollution episodes in the
      Pearl River Delta city cluster, China.
AB  - Located in the Southern China monsoon region, pollution days in Pearl River Delta
      (PRD) were classified into "Western type", "Central type" or "Eastern type", with
      a relative percentage of 67%, 24% and 9%, respectively. Using this classification
      system, three typical pollution events were selected for numerical simulations
      using the WRF-Chem model. The source sensitivity method for anthropogenic
      emissions of PM2.5 and its precursors was applied to identify the source-receptor
      relationships for PM2.5 among 9 cities in PRD. For "Western type" case, the PRD
      region was under control of a high-pressure system with easterly prevailing
      winds. The PM2.5 concentrations in the western PRD region were higher than those
      in the eastern region, with emissions from cities in the eastern PRD region
      having higher contributions. Within the PRD's urban cluster, PM2.5 in Huizhou,
      Dongguan and Shenzhen was mainly derived from local emissions, whereas the PM2.5
      in the other cities was primarily derived from external transport. For "Eastern
      type" case, the PRD was influenced by Typhoon Soulik with westerly prevailing
      winds. Emissions from cities in the western PRD region had the highest impacts on
      the overall PM2.5 concentration. PM2.5 in Jiangmen and Foshan was primarily
      derived from local emissions. Regarding "Central type" case, the PRD region was
      under control of a uniform pressure field with low wind speed. PM2.5
      concentrations of each city were primarily caused by local emissions. Overall,
      wind flows played a significant role in the transport and spatial distribution of
      PM2.5 across the PRD region. Ideally, local governments would be wise to
      establish joint prevention and control measures to reduce regional atmospheric
      pollution, especially for "Western type" pollution.

PMID- 28432910
TI  - Total mercury levels in hair of children aged 7years before and after the Great
      East Japan Earthquake.
AB  - The Great East Japan Earthquake on March 11, 2011 caused severe damage to the
      Sanriku coastal area, where we have been conducting a birth cohort study. The
      disaster occurred in the middle of 7-year-old examination. The mother-child pairs
      who participated in our study were compulsorily divided into two groups: the
      examination was finished for 157 children before the disaster, and for 335 after
      the disaster. We examined whether the disaster affected total mercury (THg)
      levels of the cohort, as well as a relationship between the THg levels at birth
      and at present. Although there was no significant difference between the
      predisaster and postdisaster groups for THg levels in cord blood (16.3 and
      16.1ngg-1, respectively) or maternal hair at parturition (2.57 and 2.55MUgg-1,
      respectively), the THg in hair of the 7-year-old children was significantly lower
      in the postdisaster group (1.79MUgg-1) than in the predisaster group (2.51MUgg
      1). The difference remained significant after adjusting for the prenatal exposure
      level of THg. In the 492 mother-child pairs, the cord-blood THg was significantly
      correlated with the THg in maternal hair at parturition (r=0.846) and in hair of
      the 7-year-old children (r=0.147). In conclusion, the 29% decrease in hair THg
      after the disaster appears to have been due to the fact that children in the
      affected area could not consume fish/seafood as usual, probably because of
      destructive damage to the fishery. Nevertheless, the THg levels at 7years of age
      reflected the prenatal exposure levels to some extent.

PMID- 28432911
TI  - Lifting the lid on geographic complexity in the relationship between body mass
      index and education in China.
AB  - In China, rising obesity has coincided with increasing affluence. Few studies
      have properly accounted for geographic variation, however, which may influence
      prior results. Using large data with biomarkers in China, we show body mass index
      (BMI) to be positively correlated with higher person-level education if estimated
      using ordinary least squares. In stark contrast, fitting the same data within a
      multilevel model gives the complete opposite result. We go on to show that the
      relationship between BMI and person-level education in China is dependent upon
      geography, underlining why multilevel modelling is crucial for revealing these
      types of people-place contingencies.

PMID- 28432912
TI  - The embodied spaces of children with complex care needs: Effects on the social
      realities and power negotiations of families.
AB  - This paper presents research findings that advance knowledge around the power and
      agency families with children with complex care needs (CCN). Our conceptual
      framework uses concepts from geography towards situating the experiences and
      social realities of family carers within the 'embodied space of care'. The data
      originate from a longitudinal qualitative study of Canadian families with
      children with CCN. Findings reveal that interactions and decision-making
      processes relating to health and everyday life were complex and socially
      interconnected, and emphasize the need for provisions for family-based decision
      making and enhanced social inclusion of families and the importance of the
      renegotiation of power.

PMID- 28432913
TI  - Spontaneously formed redox- and pH-sensitive polymersomes by mPEG based
      cytocompatible random copolymers.
AB  - Stimuli-sensitive polymersomes are one of the important vehicles and have been
      extensively studied as smart drug delivery system. Polymersomes have added
      advantage over the micelles because of having the ability to carry not only
      hydrophobic but also hydrophilic guest in their aqueous core. Among various
      stimuli, the change of pH and redox reaction is very important for drug delivery
      purpose especially for anticancer drug. Therefore, in this work, two
      poly(ethylene glycol) methyl ether methacrylate (mPEG) containing hydrophilic
      random anionic copolymers, poly[(2-hydroxyethyl methacrylate-3,3'
      dithiodipropanoic acid)x-co-(poly(ethylene glycol) methyl ether methacrylate)y],
      poly[(HEMA-DTDPA)x-co-mPEGy] with different copolymer ratios were designed and
      synthesized. The self-assembly behaviour of these copolymers were studied by use
      of various techniques, including fluorescence spectroscopy, light scattering, and
      electron and optical microscopy. Both the copolymers were observed to form
      negatively charged polymersomes spontaneously in aqueous media at pH 7. The
      polymersomes were shown to successfully encapsulate hydrophobic as well as
      hydrophilic guests. The polymersomes of both the polymers showed pH- and redox
      sensitive release of encapsulated guest leading to a very good system for
      cytoplasmic delivery. The polymers were found to be nontoxic and hemocompatible
      up to a reasonably high concentration. Also the polymers did not show any
      denaturizing effect on the secondary structure of carrier protein, human serum
      albumin. It was concluded that these two dual stimuli-sensitive cytocompatible
      polymersomes can have potential use as drug delivery system in cancer
      chemotherapy.

PMID- 28432914
TI  - Adaptive optimization of ultrasound beamforming sound velocity using sub-aperture
      differential phase gradient.
AB  - Ultrasound array imaging systems rely on a presumed beamforming sound velocity to
      calculate the time compensation of each element for receive focusing. The
      mismatch between the tissue sound velocity and the beamforming sound velocity can
      degrade the focusing quality due to loss of phase coherence. Since the tissue
      sound velocity cannot be known in prior, an adaptive optimization of beamforming
      sound velocity is required to improve the image quality. Differential phase
      gradient of channel data is proposed to estimate the optimal sound velocity for
      beamforming. The sound velocity optimization is achieved when the differential
      phase gradient between the left and the right sub-apertures approaches zero.
      Channel-domain autocorrelation is utilized for the estimation of phase gradient
      due to its high rejection to noise interference and low computational complexity.
      Results indicate that, compared to the conventional phase variance method, the
      proposed differential phase gradient reduces the standard deviation of sound
      velocity estimation from 0.5% to 0.2% while the accuracy remains comparable. The
      contrast ratio of the cyst region achieves the peak when the optimized sound
      velocity is utilized for beamforming. The lateral resolution of point target also
      improves by 14.3% after sound velocity optimization. The proposed method
      increases the robustness of sound velocity optimization. It is suggested to be
      implemented at transmit focal depth and without beam steering for better
      performance.

PMID- 28432915
TI  - Proton-induced production and radiochemical isolation of 44Ti from scandium metal
      targets for 44Ti/44Sc generator development.
AB  - Scandium-44g (half-life 3.97h) shows promise for application in positron emission
      tomography (PET), due to favorable decay parameters. One of the sources of 44gSc
      is the 44Ti/44gSc generator, which can conveniently provide this radioisotope on
      a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn,
      can be obtained via proton irradiation of scandium metal targets. A substantial
      44Ti product batch, however, requires high beam currents, long irradiation times
      and an elaborate chemical procedure for 44Ti isolation and purification. This
      study describes the production of a combined 175MBq (4.7mCi) batch yield of 44Ti
      in week long proton irradiations at the Los Alamos Isotope Production Facility
      (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion
      exchange chromatography based chemical separation method is introduced: first, a
      coarse separation of 44Ti via anion exchange sorption in concentrated HCl results
      in a 44Tc/Sc separation factor of 102-103. A second, cation exchange based step
      in HCl media is then applied for 44Ti fine purification from residual Sc mass. In
      summary, this method yields a 90-97% 44Ti recovery with an overall Ti/Sc
      separation factor of >=106.

PMID- 28432917
TI  - Chiral recognition of phenylglycinol enantiomers based on N-acetyl-l-cysteine
      capped CdTe quantum dots in the presence of Ag.
AB  - In this study, a novel method for chiral recognition of phenylglycinol (PG)
      enantiomers was proposed. Firstly, water-soluble N-acetyl-l-cysteine (NALC)
      capped CdTe quantum dots (QDs) were synthesized and experiment showed that the
      fluorescence intensity of the reaction system slightly enhancement when added PG
      enantiomers to NALC-capped CdTe quantum dots (QDs), but the R-PG and S-PG could
      not be distinguished. Secondly, when there was Ag+ presence in the reaction
      system, the experiment result was extremely interesting, the PG enantiomers cloud
      make NALC-capped CdTe QDs produce different fluorescence signal, in which the
      fluorescence of S-PG+Ag++NALC-CdTe system was significantly enhanced, and the
      fluorescence of R-PG+Ag++NALC-CdTe system was markedly decreased. Thirdly, all
      the enhanced and decreased of the fluorescence intensity were directly
      proportional to the concentration of R-PG and S-PG in the linearly range 10-5-10
      7mol.L-1, respectively. So, the new method for simultaneous determination of the
      PG enantiomers was built too. The experiment result of the method was
      satisfactory with the detection limit of PG can reached 10-7mol.L-1 and the
      related coefficient of S-PG and R-PG are 0.995 and 0.980, respectively. The
      method was highly sensitive, selective and had wider detection range compared
      with other methods.

PMID- 28432916
TI  - Colorimetric method for the detection of melamine using in-situ formed silver
      nanoparticles via tannic acid.
AB  - Melamine toxicity has recently attracted worldwide attention as it causes renal
      failure and the death of humans and animals. Therefore, developing a simple, fast
      and sensitive method for the routine detection of melamine is the need of the
      hour. Herein, we have developed a selective colorimetric method for the detection
      of melamine in milk samples based upon in-situ formation of silver nanoparticles
      (AgNPs) via tannic acid. The AgNPs thus formed were characterized by UV-Visible
      spectrophotometer, transmission electron microscope (TEM), zetasizer and dynamic
      light scattering (DLS). The AgNPs were used to detect melamine under in vitro
      condition and in raw milk spiked with melamine. Under optimal conditions,
      melamine could be selectively detected in vitro within the concentration range of
      0.05-1.4MUM with a limit of detection (LOD) of 0.01MUM, which is lower than the
      strictest melamine safety requirement of 1ppm. In spiked raw milk, the recovery
      percentage range was 99.5-106.5% for liquid milk and 98.5-105.5% for powdered
      milk. The present method shows extreme selectivity with no significant
      interference with other substances like urea, glucose, glycine, ascorbic acid
      etc. This assay method does not utilize organic cosolvents, enzymatic reactions,
      light sensitive dye molecules and sophisticated instrumentation, thereby
      overcoming some of the limitations of the other conventional methods.

PMID- 28432918
TI  - A quinoline-based Cu2+ ion complex fluorescence probe for selective detection of
      inorganic phosphate anion in aqueous solution and its application to living
      cells.
AB  - A quinaldine functionalized probe QP has been designed and synthesized. It
      exhibited selective turn-off fluorescence response toward Cu2+ ion over most of
      the biologically important ions at physiological pH. The binding ratio of the
      probe QP and Cu2+ ion was determined to be 1:1 through fluorescence titration,
      Job's plot and ESI-MS. The binding constant (K) of Cu2+ to probe QP was found to
      be 2.12*104M-1. Further, the Cu2+ ensemble of probe QP was found to respond H2PO4
      and HPO42- among other important biological anions via fluorescence turn-on
      response at physiological pH. Fluorescence microscopy imaging using living Hela
      cells showed that probe QP could be used as an effective fluorescent probe for
      detecting Cu2+ cation and H2PO4- and HPO42- anions in living cells.

PMID- 28432919
TI  - Synthesis, fluorescence-sensing and molecular logic of two water-soluble 1,8
      naphthalimides.
AB  - Two novel highly water-soluble fluorescence sensing 1,8-naphthalimides are
      synthesized and investigated. The novel compounds are designed on the
      "fluorophore-receptor1-spacer-receptor2" model as a molecular fluorescence probe
      for determination of cations and anions in 100% aqueous media. The novel probes
      comprising N-imide and N-phenylpiperazine or morpholine substituents are capable
      to operate simultaneously via ICT and PET signaling mechanism as a function of pH
      and to recognize selectively Cu2+ and Hg2+ over the other representative metal
      ions. Due to the remarkable fluorescence changes in the presence of protons,
      hydroxyl anions, Hg2+ and Cu2+, INH and doubly disabled INH logic gates are
      executed and the systems are able to act as a single output combinatorial logic
      circuit with four chemical inputs.

PMID- 28432920
TI  - Health, family strains, dependency, and life satisfaction of older adults.
AB  - Using stress process theory and structural equation modelling, this study
      investigated the complex relationship between health status, family strain,
      dependency, and the life satisfaction of rural older adults with reported
      functional impairments in India. Data were extracted from a large-scale study of
      903 randomly selected adults aged 61 years and older from 30 rural clusters of
      India. The sample for this study was confined to 653 older adults who reported
      functional impairments. Structural equation modelling showed that poor health
      status indirectly lowered the life satisfaction of older adults through family
      strains. Moreover, poor health status also indirectly influenced life
      satisfaction through dependency and family strain (poor health->dependency
      >family strains->life satisfaction). The findings indicate that for professionals
      who deal with the health of older adults, exploring relationship strains and
      dependency is vital to the assessment and intervention of subjective wellbeing.
      Inter-sectoral coordination and communication between healthcare and social
      service agencies might facilitate effective management of health problems among
      older adults. Moreover, taking family strains and dependency into account when
      caring for older adults with health problems is critical to help improve their
      quality of life and maintain their wellbeing.

PMID- 28432921
TI  - Gates for soluble and membrane proteins, and two trafficking systems (IFT and
      LIFT), establish a dynamic ciliary signaling compartment.
AB  - Primary cilia are microtubule-based organelles found on most mammalian cell
      surfaces. They possess a soluble matrix and membrane contiguous with the cell
      body cytosol and plasma membrane, and yet, have distinct compositions that can be
      modulated to enable dynamic signal transduction. Here, we discuss how specialized
      ciliary compartments are established using a coordinated network of gating,
      trafficking and targeting activities. Cilium homeostasis is maintained by a size
      selective molecular mesh that limits soluble protein entry, and by a membrane
      diffusion barrier localized at the transition zone. Bidirectional protein
      shuttling between the cell body and cilium uses IntraFlagellar Transport (IFT),
      and prenylated ciliary protein delivery is achieved through Lipidated protein
      IntraFlagellar Targeting (LIFT). Elucidating how these gates and transport
      systems function will help reveal the roles that cilia play in ciliary signaling
      and the growing spectrum of disorders termed ciliopathies.

PMID- 28432922
TI  - Restricted access magnetic core-mesoporous shell microspheres with C8-modified
      interior pore walls for the identification of 20(S)-protopanaxadiol metabolites
      in rat plasma using UPLC-Q-TOF-MS/MS.
AB  - In the present study, a novel sample preparation method based on magnetic core
      mesoporous shell microspheres with C8-modified interior pore walls (C8
      Fe3O4@mSiO2) was established for the identification of 20(S)-protopanaxadiol
      (PPD) metabolites in rat plasma by UPLC-Q-TOF-MS/MS analysis. C8-Fe3O4@mSiO2
      allowed selective extraction of PPD metabolites from rat plasma by excluding
      macromolecules in the plasma owing to size exclusion effect. Five extraction
      conditions including the amount of C8-Fe3O4@mSiO2 microspheres used, extraction
      time, elution solvents, elution volume, and elution time were investigated and
      optimized. The present method was compared with two conventional sample
      preparation methods: protein precipitation and C8 solid phase extraction (C8
      SPE). Our method provided higher UPLC intensity of result than protein
      precipitation method. While the resulting intensity of our method and that of C8
      SPE were not significantly different, it consumed less processing time (15min 55s
      for C8-Fe3O4@mSiO2, and 27min 30s for C8-SPE). Finally, the proposed method was
      successfully applied in the identification of PPD metabolites in vivo, in which a
      total of 17 metabolites and the parent drug were identified in rat plasma.

PMID- 28432923
TI  - Triterpenoid saponins from the roots of Spergularia marginata.
AB  - Phytochemical investigations of the roots of Spergularia marginata had led to the
      isolation of four previously undescribed triterpenoid saponins, a known one and
      one spinasterol glycoside. Their structures were established by extensive NMR and
      mass spectroscopic techniques as 3-O-beta-D-glucuronopyranosyl echinocystic acid
      28-O-alpha-L-arabinopyranosyl-(1 -> 2)-alpha-L-rhamnopyranosyl-(1 -> 3)-beta-D
      xylopyranosyl-(1 -> 4)-alpha-L-rhamnopyranosyl-(1 -> 2)-alpha-L- arabinopyranosyl
      ester, 3-O-beta-D-glucopyranosyl-(1 -> 3)-beta-D-glucuronopyranosyl echinocystic
      acid 28-O-alpha-L-arabinopyranosyl-(1 -> 2)-alpha-L-rhamnopyranosyl-(1 -> 3)-beta
      D-xylopyranosyl-(1 -> 4)-alpha-L-rhamnopyranosyl-(1 -> 2)- alpha-L
      arabinopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1 -> 4)-3-O-sulfate-beta-D
      glucuronopyranosyl echinocystic acid 28-O-alpha-L-arabinopyranosyl-(1 -> 2)-alpha
      L-rhamnopyranosyl-(1 -> 3)-beta-D-xylopyranosyl-(1 -> 4)-alpha-L-rhamnopyranosyl
      (1 -> 2)-alpha-L-arabinopyranosyl ester, and 3-O-beta-D-glucopyranosyl-(1 -> 4)
      beta-D-glucuronopyranosyl 21-O-acetyl acacic acid. Their cytotoxicity was
      evaluated against two human cancer cell lines SW480 and MCF-7. The most active
      compound showed a cytotoxicity with IC50 14.2 +/- 0.8 MUM (SW480), and 18.7 +/-
      0.8 MUM (MCF-7), respectively.

PMID- 28432924
TI  - Bringing a novel to practice: An interpretive study of reading a novel in an
      undergraduate nursing practicum course.
AB  - Novels are one humanities resource available to educators in health disciplines
      to support student reflection on their own professional practice and therapeutic
      relationships with patients. An interdisciplinary team, including nurses, a
      physician, and an English instructor, carried out an interpretive study of the
      use of a novel by clinical nursing instructors in an undergraduate practicum
      course. Students placed in assisted living or long term care facilities for the
      elderly were expected to read a contemporary work, Exit Lines, by Joan Barfoot,
      which is set in a comparable facility. The objective was to increase
      understanding of the meanings that participants ascribed to the novel reading
      exercise in relation to their development as student nurses. By using a
      hermeneutic approach, we used dialogue throughout the study to elicit
      perspectives among participants and the interdisciplinary research team. Major
      themes that emerged included the students' tacit awareness of epistemological
      plurality in nursing, and the consequent importance of cultivating a capacity to
      move thoughtfully between different points of view and ways of knowing.

PMID- 28432925
TI  - Structure of the S1 subunit C-terminal domain from bat-derived coronavirus HKU5
      spike protein.
AB  - Accumulating evidence indicates that MERS-CoV originated from bat coronaviruses
      (BatCoVs). Previously, we demonstrated that both MERS-CoV and BatCoV HKU4 use
      CD26 as a receptor, but how the BatCoVs evolved to bind CD26 is an intriguing
      question. Here, we solved the crystal structure of the S1 subunit C-terminal
      domain of HKU5 (HKU5-CTD), another BatCoV that is phylogenetically related to
      MERS-CoV but cannot bind to CD26. We observed that the conserved core subdomain
      and those of other betacoronaviruses (betaCoVs) have a similar topology of the
      external subdomain, indicating the same ancestor of lineage C betaCoVs. However,
      two deletions in two respective loops located in HKU5-CTD result in
      conformational variations in CD26-binding interface and are responsible for the
      non-binding of HKU5-CTD to CD26. Combined with sequence variation in the HKU5-CTD
      receptor binding interface, we propose the necessity for surveilling the mutation
      in BatCoV HKU5 spike protein in case of bat-to-human interspecies transmission.

PMID- 28432926
TI  - Tick-borne encephalitis virus infects human brain microvascular endothelial cells
      without compromising blood-brain barrier integrity.
AB  - Alteration of the blood-brain barrier (BBB) is a hallmark of tick-borne
      encephalitis (TBE), a life-threating human viral neuroinfection. However, the
      mechanism of BBB breakdown during TBE, as well as TBE virus (TBEV) entry into the
      brain is unclear. Here, primary human microvascular endothelial cells (HBMECs)
      were infected with TBEV to study interactions with the BBB. Although the number
      of infected cells was relatively low in culture (<5%), the infection was
      persistent with high TBEV yields (>106pfu/ml). Infection did not induce any
      significant changes in the expression of key tight junction proteins or
      upregulate the expression of cell adhesion molecules, and did not alter the
      highly organized intercellular junctions between HBMECs. In an in vitro BBB
      model, the virus crossed the BBB via a transcellular pathway without compromising
      the integrity of the cell monolayer. The results indicate that HBMECs may support
      TBEV entry into the brain without altering BBB integrity.

PMID- 28432927
TI  - Type 2 BVDV Npro suppresses IFN-1 pathway signaling in bovine cells and augments
      BRSV replication.
AB  - Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in
      conjunction with bovine respiratory syncytial virus (BRSV) contributes to the
      bovine respiratory disease complex. Bovine turbinate cells were single or co
      infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional Npro mutant
      (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF
      3, and IFN-beta mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed
      significantly up-regulated PKR, IRF-3, IRF-7, and IFN-beta mRNAs, whereas BVDV2
      wt, but not BVDV2-E, abolished this up-regulation in co-infection. No significant
      differences were observed in MAVS, NF-kappaB, and PIN-1 mRNAs. A dual-luciferase
      reporter assay showed that BVDV2-wt significantly increased NF-kappaB activity
      compared to BVDV2-E, while BVDV2-E significantly increased IFN-beta activity
      compared to BVDV2-wt. The BRSV titer and RNA levels significantly increased in
      cells co-infected with BRSV/BVDV2-wt compared to cells co-infected with
      BRSV/BVDV2-E or infected with BRSV alone. This data supports the synergistic
      action of BVDV2-wt and BRSV inhibition of IFN-1.

PMID- 28432929
TI  - Performance testing of the neutron flux monitors from 10keV to 1MeV developed for
      BNCT: A preliminary study.
AB  - The neutron flux monitors from 10keV to 1MeV designed for boron neutron capture
      therapy (BNCT) were experimentally tested with prototype monitors in an
      appropriate neutron field produced at the intense deuterium-tritium neutron
      source facility OKTAVIAN of Osaka University, Japan. The experimental test
      results and related analysis indicated that the performance of the monitors was
      good and the neutron fluxes from 10keV to 1MeV of practical BNCT neutron sources
      can be measured within 10% by the monitors.

PMID- 28432928
TI  - A humanized mouse-based HIV-1 viral outgrowth assay with higher sensitivity than
      in vitro qVOA in detecting latently infected cells from individuals on ART with
      undetectable viral loads.
AB  - Assays that can verify full viral eradication are essential in the context of
      achieving a cure for HIV/AIDS. In vitro quantitative viral out growth assays
      (qVOA) are currently the gold standard for measuring latent HIV-1 but these
      assays often fail to detect very low levels of replication-competent virus. Here
      we investigated an alternative in vivo approach for sensitive viral detection
      using humanized mice (hmVOA). Peripheral blood CD4+ T cell samples from HIV
      subjects on stable ART with undetectable viral loads by RT-PCR were first assayed
      by in vitro qVOA. Corresponding patient samples in which no virus was detected by
      qVOA were injected into humanized mice to allow viral outgrowth. Of the five qVOA
      virus negative samples, four gave positive viral outgrowth in the hmVOA assay
      suggesting that it is more sensitive in detecting latent HIV-1.

PMID- 28432930
TI  - An innovative procedure for NORM scales treatment and radionuclides separation.
AB  - The present study focuses on the development of a new chemical treatment method
      for naturally occurring radioactive materials (NORM) scale wastes from the oil
      industry. The method consists of three-stages, including the separation of oil
      using the Fenton oxidation process at room temperature, the complete dissolution
      of soluble and slightly soluble salts and separation of Ra and Pb isotopes. The
      proposed method can be considered as an innovative procedure for NORM scales
      treatment and radionuclides separation, which in turn support the radioactive
      waste management with economic benefits.

PMID- 28432931
TI  - Acute appendicitis presenting as an abdominal wall abscess: A case report.
AB  - INTRODUCTION: Amyand hernia (AH) is a rare type of hernia characterized by the
      presence of appendix vermiformis in the inguinal hernial sac. It is rarely
      reported in women. PRESENTATION OF CASE: We presented a case of a 60- year old
      woman who was admitted initially with an abdominal wall abscess and found to have
      perforated appendix in the right inguinal hernia. The patient underwent standard
      open appendectomy and the post-operative course was uneventful. DISCUSSION: The
      initial presentation of our case as an abdominal wall abscess is rare in the
      contemporary literature. CONCLUSIONS: A high index of suspicious, early diagnosis
      and timely surgical intervention are the keys to have favorable outcome in amyand
      hernia. The management should follow general guidelines of appendectomy, hernia
      repair and dealing with the associated pathology if present.

PMID- 28432932
TI  - Surveillance of Vittaforma corneae in hot springs by a small-volume procedure.
AB  - Vittaforma corneae is an obligate intracellular fungus and can cause human ocular
      microsporidiosis. Although accumulating reports of V. corneae causing
      keratoconjunctivitis in both healthy and immunocompromised persons have been
      published, little is known about the organism's occurrence in aquatic
      environments. Limitations in detection sensitivity have meant a large sampling
      volume is required to detect the pathogen up to now, which is problematic. A
      recent study in Taiwan has shown that some individuals suffering from
      microsporidial keratitis (MK) were infected after exposure to the pathogen at a
      hot spring. As a consequence of this, a survey and analysis of environmental V.
      corneae present in hot springs became an urgent need. In this study, sixty water
      samples from six hot spring recreation areas around Taiwan were analyzed. One
      liter of water from each sample site was filtered to harvest the fungi. The
      positive samples were detected using a modified nested PCR approach followed by
      sequencing using specific SSU rRNA gene primer pairs for V. corneae. In total
      fifteen V. corneae-like isolates were identified (25.0% of sites). Among them,
      six isolates, which were collected from recreational areas B, C and D, were
      highly similar to known V. corneae keratitis strains from Taiwan and other
      countries. Furthermore, five isolates, which were collected from recreation areas
      A, C, E and F, were very similar to Vittaforma-like diarrhea strains isolated in
      Portugal. Cold spring water tubs and public foot bath pools had the highest
      detection rate (50%), suggesting that hot springs might be contaminated via
      untreated water sources. Comparing the detection rate across different regions of
      Taiwan, Taitung, which is in the east of the island, gave the highest positive
      rate (37.5%). Statistical analysis showed that outdoor/soil exposure and a high
      heterotrophic plate count (HPC) were risk factors for the occurrence of V.
      corneae. Our findings provide empirical evidence supporting the need for proper
      control and regulations at hot spring recreational waters in order to avoid
      health risks from this pathogen. Finally, we have developed a small volume
      procedure for detecting V. corneae in water samples and this has proved to be
      very useful.

PMID- 28432934
TI  - J.S. Athertya, G. Saravana Kumar, "Automatic segmentation of vertebral contours
      from CT images using fuzzy corners" [Comput. Biol. Med. 72 (May 1, 2016) 75-89,
      https://www.ncbi.nlm.nih.gov/pubmed/27017068].

PMID- 28432933
TI  - (Non-)symbolic magnitude processing in children with mathematical difficulties: A
      meta-analysis.
AB  - Symbolic and non-symbolic magnitude representations, measured by digit or dot
      comparison tasks, are assumed to underlie the development of arithmetic skills.
      The comparison distance effect (CDE) has been suggested as a hallmark of the
      preciseness of mental magnitude representations. It implies that two magnitudes
      are harder to discriminate when the numerical distance between them is small, and
      may therefore differ in children with mathematical difficulties (MD), i.e. low
      mathematical achievement or dyscalculia. However, empirical findings on the CDE
      in children with MD are heterogeneous, and only few studies assess both symbolic
      and non-symbolic skills. This meta-analysis therefore integrates 44 symbolic and
      48 non-symbolic response time (RT) outcomes reported in nineteen studies (N=1630
      subjects, aged 6-14 years). Independent of age, children with MD show
      significantly longer mean RTs than typically achieving controls, particularly on
      symbolic (Hedges' g=0.75; 95% CI [0.51; 0.99]), but to a significantly lower
      extent also on non-symbolic (g=0.24; 95% CI [0.13; 0.36]) tasks. However, no
      group differences were found for the CDE. Extending recent work, these meta
      analytical findings on children with MD corroborate the diagnostic importance of
      magnitude comparison speed in symbolic tasks. By contrast, the validity of CDE
      measures in assessing MD is questioned.

PMID- 28432935
TI  - Accelerometry-based assessment and detection of early signs of balance deficits.
AB  - Falls are the cause for more than half of the injury-related hospitalizations
      among older people. Accurate assessment of individuals' fall risk could enable
      targeted interventions to reduce the risk. This paper presents a novel method for
      using wearable accelerometers to detect early signs of deficits in balance from
      gait. Gait acceleration data were analyzed from 35 healthy female participants
      (73.86+/-5.40 years). The data were collected with waist-mounted accelerometer
      and the participants performed three supervised balance tests: Berg Balance Scale
      (BBS), Timed-Up-and-Go (TUG) and 4m walk. The follow-up tests with the same
      protocol were performed after one year. Altogether 43 features were extracted
      from the accelerometer signals. Sequential forward floating selection and ten
      fold cross-validation were applied to determine models for 1) estimating the
      outcomes of BBS, TUG and 4m walk tests and 2) predicting decline in balance
      during one-year follow-up indicated as decline in BBS total score and one leg
      stance. Normalized root-mean-square errors (RMSE) of the assessment scale result
      estimates were 0.28 for BBS score, 0.18 for TUG time, and 0.22 for 4m walk test.
      Area under curve (AUC) was 0.78 for predicting decline in BBS total score and
      0.82 for one leg stance, respectively. The results suggest that the gait features
      can be used to estimate the result of a clinical balance assessment scale and
      predict decline in balance. A simple walk test with wearable monitoring could be
      applicable as an initial screening tool to identify people with early signs of
      balance deficits.

PMID- 28432936
TI  - The immunosuppressive characteristics of FB1 by inhibition of maturation and
      function of BMDCs.
AB  - Fumonisin B1 (FB1) is one kind of mycotoxins that has the neurotoxicity,
      carcinogenicity, hepatotoxicity and immunotoxicity produced by the fungus
      Fusarium verticillioides, which commonly infects corn and other crops and is
      harmful to animal and human health upon consumption of FB1-contaminated feed or
      food. However, the mechanism of immunotoxicity, especially the immunosuppression
      induced by FB1 is still unclear. The most pivotal cells in the induction of
      immune responses are dendritic cells (DCs). In this study, we used murine bone
      marrow-derived dendritic cells (BMDCs) as a model system to elucidate the effect
      of FB1 on the function of BMDCs through biological methods. We found that FB1
      reversed the morphological changes and enhanced the endocytosis of FITC-dextran
      in LPS-treated BMDCs. At the same time, FB1 decreased the LPS-induced expressions
      of MHC II, C[1]D80 and CD86 molecules in BMDCs (p<0.05), as well as the T-cell
      stimulatory capacity of BMDCs (p<0.01). Moreover, the secretions of IL-6, IL-10
      and IL-12, but not TNF-alpha induced by LPS exposure were suppressed by FB1 in a
      dose dependent (p<0.01). It was considered that the immunosuppressive effects of
      FB1 were mainly caused by changing the morphology and interfering with the
      process of antigen uptake, processing and presentation. The results highlighted
      that FB1 had the capacity to modulate the immune responses of BMDCs.

PMID- 28432937
TI  - Subantibiotic dose of azithromycin attenuates alveolar bone destruction and
      improves trabecular microarchitectures in a rat model of experimental
      periodontitis: A study using micro-computed tomography.
AB  - Azithromycin, a macrolide antibiotic, has anti-inflammatory and immunomodulatory
      activities apart from its antibacterial properties. In this study, we examined
      the efficacy of subantibiotic dose of azithromycin on ligature-induced
      periodontitis in rats using micro-computed tomography (micro-CT) imaging and bone
      parameter analysis. Male Sprague-Dawley rats were allocated to the following four
      groups: non-ligation (NL) group; ligation-only (L) group; ligation-plus
      subantibiotic dose azithromycin (SA) group; and 4) ligation-plus-antibiotic dose
      azithromycin (AA) group. The rats from Groups L, SA and AA were subjected to
      periodontitis by placing a ligature around lower right first molar. Immediately
      after ligation, the rats in SA and AA groups received daily intraperitoneal
      injections of azithromycin at a dosage of 3.5 or 10mg/kg body weight,
      respectively. The ligatures were maintained for 2weeks at which time the rats had
      their mandibles hemisected for micro-CT analysis. Subantibiotic dose of
      azithromycin strongly suppressed reductions in alveolar bone height and bone
      volume fraction caused by experimental periodontitis. When subantibiotic dosage
      of azithromycin was administered to rats, ligature-induced alterations in
      microarchitectural parameters of trabecular bone were significantly reversed.
      Rats treated with subantibiotic dose of azithromycin presented no significant
      difference compared to rats with antibiotic dosage in all parameters. While
      further studies are necessary, subantibiotic dose of azithromycin could be
      utilized as a host modulator for the treatment of periodontitis.

PMID- 28432938
TI  - The role of distress intolerance in the relationship between childhood sexual
      abuse and problematic alcohol use among Latin American MSM.
AB  - BACKGROUND: Despite the high prevalence of childhood sexual abuse (CSA) among men
      who have sex with men (MSM) and its well-documented association with substance
      use in adulthood, little research has examined the psychological mechanisms
      underlying this association. The current study utilized a large, multinational
      sample of MSM in Latin America to examine the role of distress intolerance (i.e.,
      decreased capacity to withstand negative psychological states) in the
      relationship between childhood sexual abuse history and problematic alcohol use.
      METHODS: As part of an online survey conducted among members of the largest
      social/sexual networking website for MSM in Latin America, participants
      (n=19,451) completed measures of childhood sexual abuse history, distress
      intolerance, and problematic alcohol use (CAGE score>=2). RESULTS: Participants
      who reported a history of childhood sexual abuse indicated higher levels of
      distress intolerance, which was in turn associated with greater odds of engaging
      in problematic alcohol use. A mediation analysis further showed that distress
      intolerance partially accounted for the significant association between childhood
      sexual abuse history and problematic alcohol use. CONCLUSION: These findings
      provide initial evidence for the role of distress intolerance as a process
      through which early trauma shapes MSM health later in life. These findings also
      underscore the potential utility of addressing distress intolerance in alcohol
      use prevention and intervention efforts that target MSM with a history of
      childhood sexual abuse.

PMID- 28432940
TI  - A sandwich immunoassay for brucellosis diagnosis based on immune magnetic beads
      and quantum dots.
AB  - Brucellosis is a serious zoonosis with a rapid increase in incidence across
      epidemic regions. Currently, there are numerous methods for diagnosing
      brucellosis. However, these studies often have a few defects, such as low
      sensitivity, poor specificity, time consuming, laborious, and even potential
      biological risk. To overcome these shortcomings, we have developed a rapid,
      sensitive and accurate diagnosis procedure for brucellosis based on the immune
      magnetic beads (IMB) probe and quantum dots (QDs) - staphylococcal protein A
      (SPA) probe. With the presence of Brucella antibody in the tested serum, the QDs
      SPA probe links to the IMB probe and an immune-sandwich complex is formed. As a
      result, the fluorescence intensity from QDs increased significantly and was
      correlated with the amount of Brucella antibody. Under the optimized conditions,
      248 blood samples were detected and the diagnosis effect was evaluated. The area
      under the receiver-operating characteristic (ROC) curve was 0.970 (95% confidence
      interval (CI), 0.9479-0.9920). The diagnostic sensitivity was 96.15% (95% CI,
      91.82-98.58%), the diagnostic specificity was 94.12% (95% CI, 87.64-97.81%) with
      a fluorescence intensity cutoff value of 150.4 and the detection time was only
      100min. This diagnostic procedure can be satisfactorily applied to the diagnosis
      of brucellosis.

PMID- 28432939
TI  - The association of psychiatric comorbidity with treatment completion among
      clients admitted to substance use treatment programs in a U.S. national sample.
AB  - BACKGROUND: Psychiatric disorders are highly comorbid with substance use
      disorders and play an important role in their course and recovery. However, the
      impact of comorbidity on treatment outcomes has not been examined in a U.S.
      national sample. This study explores the impact of psychiatric comorbidity on
      treatment completion among individuals admitted to publicly funded substance use
      treatment facilities across the United States. METHODS: Using data on first-time
      treatment episodes in the U.S. from the Treatment Episode Dataset-Discharges
      (TEDS-D) for the years 2009-2011, logistic regression was used to assess the
      association between psychiatric comorbidity and treatment non-completion, and Cox
      proportional hazards regression was used to assess the association between
      comorbidity and rate of attrition. Analyses were performed for all substances
      together and then stratified by primary substance of abuse (alcohol, cannabis,
      stimulants, or opioids). RESULTS: Of 856,385 client treatment episodes included
      in our analysis, 28% had a psychiatric comorbidity and 38% did not complete
      treatment. After adjusting for socio-demographic and treatment characteristics,
      clients with psychiatric comorbidity had higher odds of not completing treatment
      relative to those without comorbidity [OR=1.28 (1.27-1.29)], and had an earlier
      time to attrition [HR=1.14 (1.13-1.15)]. Psychiatric comorbidity was most
      strongly associated with treatment non-completion and rate of attrition in those
      admitted primarily for alcohol [OR=1.37 (1.34-1.39); HR=1.19 (1.17-1.21),
      respectively]. CONCLUSIONS: Individuals with psychiatric comorbidities receiving
      treatment for substance use disorders face unique challenges that impact their
      ability to complete treatment. The findings call for further efforts to integrate
      treatment for psychiatric comorbidities in substance use treatment settings.

PMID- 28432941
TI  - Validation of a SPE HPLC-UV method for the quantification of a new ER-specific
      photosensitizer OR-141 in blood serum using total error concept.
AB  - The aim of this work is to develop the first validated HPLC-UV method
      quantification in blood serum for a new endoplasmic reticulum (ER)-specific
      benzophenazine photosensitizer (OR-141). A fast solid phase extraction (SPE)
      cleaning sample procedure was achieved on C18 encapped (ec) SPE cartridges and
      the separation was performed on a RP-18e column (5MUM) using an isocratic elution
      with methanol. The method has been fully validated according to accuracy profiles
      based on total error and tolerance intervals. Calibration was performed in the
      matrix and trueness (<4.25% relative bias), repeatability (<4.75% relative
      standard deviation (RSD)), intermediate precision (<5.37% RSD), selectivity,
      response function, linearity, and dilution effect were evaluated for both OR-141
      regio-isomers. Afterwards the developed method was successfully applied to
      perform the quantitative determination of OR-141 in mouse blood serum samples in
      a preliminary pharmacokinetic study.

PMID- 28432942
TI  - Insights into the diversity of NOD-like receptors: Identification and expression
      analysis of NLRC3, NLRC5 and NLRX1 in rainbow trout.
AB  - Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are
      efficient soluble intracellular sensors that activate defense mechanisms against
      pathogens. In teleost fish, the involvement of NLRs in the immune response is not
      well understood. However, recent work has evidenced the expression of different
      NLRs in response to some pathogen associated molecular patterns (PAMPs). In the
      present work, the cDNA sequence encoding three new NOD-like receptors were
      identified in Oncorhynchus mykiss, namely OmNLRC3, OmNLRC5 and OmNLRX1. Results
      showed that their sequences coded for proteins of 1135, 836 and 1010 amino acids,
      respectively. The deduced protein sequences of all receptors showed
      characteristic domains of this receptor family, such as leucine rich repeats and
      NACHT domain. Phylogenetic analysis revealed a high degree of identity with other
      NOD-like receptors and they are clustered into different families. Transcript
      expression analysis indicated that OmNLRs are constitutively expressed in liver,
      spleen, intestine, gill, skin and brain. OmNLR expression was upregulated in
      kidney and gills from rainbow trout in response to LPS. In order to give new
      insights into the function of these new NLR members, an in vitro model of immune
      stimulation was established using the rainbow trout cell line RTgill-W1.
      Expression analysis revealed that RTgill-W1 overexpressed proinflammatory
      cytokines in response to LPS and poly I:C alongside with a differential
      overexpression of OmNLRC3, OmNLRC5 and OmNLRX1. The expression of OmNLRC5 was
      further verified at the protein level by immunofluorescence. Finally, the effect
      of the overexpressed cytokines on the OmNLR expression by RTgill-W1 cells was
      assessed, suggesting a regulatory mechanism on OmNLRC3 expression. Overall,
      results suggest that O. mykiss NOD-like receptors could play a key role in the
      defense mechanisms of teleost through PAMP recognition. Future studies will focus
      on gills which could be related with a key sensor mucosal system in one of the
      most environmentally fish exposed tissues.

PMID- 28432943
TI  - Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin
      activators for the treatment of systolic heart failure.
AB  - A series of flexible urea derivatives have been synthesized and demonstrated as
      selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3
      phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 MUM = 51.1%; FS =
      18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase
      activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro
      and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1
      (3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin
      ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1
      (2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation
      = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac
      myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for
      cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are
      potent scaffold to develop as a newer cardiac myosin activator for the treatment
      of systolic heart failure.

PMID- 28432944
TI  - Phototoxic action of a zinc(II) phthalocyanine encapsulated into poloxamine
      polymeric micelles in 2D and 3D colon carcinoma cell cultures.
AB  - Photodynamic therapy is emerging as a hopeful method for the treatment of
      oncological diseases. In the search of novel therapeutic strategies for
      colorectal cancer, in this work we reported the photocytotoxic activity of a
      lipophilic zinc(II) phthalocyanine on a murine colon adenocarcinoma cell line
      (CT26 cells). The 2,9(10),16(17),23(24) tetrakis[(2
      dimethylamino)ethylsulfanyl]phthalocyaninatozinc(II), named Pc9, was encapsulated
      into Tetronic(r) 1107 polymeric poloxamine micelles (T1107) and assayed in 2D and
      3D cell cultures. We showed that the formulation Pc9-T1107 was efficient to
      reduce cell viability after photodynamic treatment both in 2D cultures (IC50 10+/
      2nM) as well as in CT26 spheroids (IC50 370+/-11nM). Cellular uptake of Pc9-T1107
      was a time- and concentration-dependent process, being the phthalocyanine
      formulation mainly incorporated into lysosomal vesicles and endoplasmic reticulum
      cisterns, but not in mitochondria. Pc9-T1107 also induced the formation of
      reactive oxygen species immediately after cell irradiation. We also found that
      the phototoxic action of Pc9-T1107 was partially reversed in the presence of
      antioxidants, such as TROLOX and N-acetyl-cysteine. In addition, we showed that
      Pc9-T1107 treatment triggered an apoptotic cell death, as suggested by the
      detection of pyknotic nuclei, the reduction in the expression levels of
      procaspase-3 and the increase in caspase-3 enzymatic activity.

PMID- 28432945
TI  - Exploring isoxsuprine hydrochloride binding with human serum albumin in the
      presence of folic acid and ascorbic acid using multispectroscopic and molecular
      modeling methods.
AB  - Isoxsuprine hydrochloride (vasodilator drug), folic acid and ascorbic acid are
      medicines which can be utilized alone or simultaneously by pregnant women. In the
      present work the competitive binding of isoxsuprine hydrochloride (ISO) with
      human serum albumin (HSA) in the absence and presence of folic acid (FOL) and
      ascorbic acid (AS) was investigated using different spectroscopic probes and
      molecular docking studies. The results of fluorescence suggested that isoxsuprine
      alone or in the presence of ascorbic acid can bind to HSA and quench the
      fluorescence of HSA with static mechanism but For HSA-folic acid-isoxsuprine
      system, dynamic type of quenching mechanisms is involved. The values of binding
      constants (KHSA-ISO~1.2*103M-1, KHSA-AS-ISO~2.1*103M-1and KHSA-FOL-ISO~0.7*103M
      1) suggested that affinity of HSA to isoxsuprine increased in the presence of
      ascorbic acid while the presence of folic acid reduced the affinity of protein to
      isoxsuprine. The results of FT-IR and circular dichroism measurements indicated
      that the binding of isoxsuprine to HSA in the absence and the presence of folic
      acid and ascorbic acid may induce conformational and microenvironmental changes
      of protein. Not only do these types of spectroscopy techniques provide all the
      information about the systems, molecular docking, also emphasizes the results and
      is employed for the identification of the active site residues, bioactive
      conformer of Isoxsuprine and their critical interactions.

PMID- 28432946
TI  - Design and synthesis of sulfonamide-substituted diphenylpyrimidines (SFA-DPPYs)
      as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward
      B-cell lymphoblastic leukemia.
AB  - A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by
      introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine
      template, and then were biologically evaluated as potent Bruton's tyrosine kinase
      (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k
      displayed high potency against the BTK enzyme, with IC50 values of 1.18 nM, 0.92
      nM, 0.42 nM and 1.05 nM, respectively. In particular, compound 10c could
      remarkably inhibit the proliferation of the B lymphoma cell lines at
      concentrations of 6.49 MUM (Ramos cells) and 13.2 MUM (Raji cells), and was
      stronger than the novel agent spebrutinib. In addition, the inhibitory potency
      toward the normal PBMC cells showed that inhibitor 10c possesses low cell
      cytotoxicity. All these explorations indicated that molecule 10c could serve as a
      valuable inhibitor for B-cell lymphoblastic leukemia treatment.

PMID- 28432947
TI  - Pretreatment of Eucalyptus in biphasic system for furfural production and
      accelerated enzymatic hydrolysis.
AB  - Herein, an efficient biphasic pretreatment process was developed to improve the
      production of furfural (FF) and glucose from Eucalyptus. The influence of formic
      acid and NaCl on FF production from xylose in water and various biphasic systems
      was investigated. Results showed that the addition of formic acid and NaCl
      significantly promoted the FF yield, and the biphasic system of MIBK (methyl
      isobutyl ketone)/water exhibited the best performance for FF production. Then the
      Eucalyptus was pretreated in the MIBK/water system, and a maximum FF yield of
      82.0% was achieved at 180 degrees C for 60min. Surface of the pretreated
      Eucalyptus became relatively rough and loose, and its crystallinity index
      increased obviously due to the removal of hemicelluloses and lignin. The
      pretreated Eucalyptus samples showed much higher enzymatic hydrolysis rates (26.2
      70.7%) than the raw Eucalyptus (14.5%).

PMID- 28432948
TI  - Butanol fermentation of the brown seaweed Laminaria digitata by Clostridium
      beijerinckii DSM-6422.
AB  - Seaweed represents an abundant, renewable, and fast-growing biomass resource for
      3rd generation biofuel production. This study reports an efficient butanol
      fermentation process carried out by Clostridium beijerinckii DSM-6422 using
      enzymatic hydrolysate of the sugar-rich brown seaweed Laminaria digitata
      harvested from the coast of the Danish North Sea as substrate. The highest
      butanol yield (0.42g/g-consumed-substrates) compared to literature was achieved,
      with a significantly higher butanol:acetone-butanol-ethanol (ABE) molar ratio
      (0.85) than typical (0.6). This demonstrates the possibility of using the seaweed
      L. digitata as a potential biomass for butanol production. For the first time,
      consumption of alginate components was observed by C. beijerinckii DSM-6422. The
      efficient utilization of sugars and lactic acid further highlighted the potential
      of using this strain for future development of large-scale cost-effective butanol
      production based on (ensiled) seaweed.

PMID- 28432949
TI  - Dominance of candidate Saccharibacteria in a membrane bioreactor treating medium
      age landfill leachate: Effects of organic load on microbial communities,
      hydrolytic potential and extracellular polymeric substances.
AB  - A membrane bioreactor (MBR), accomplishing high nitrogen removal efficiencies,
      was evaluated under various landfill leachate concentrations (50, 75 and 100%
      v/v). Proteinous and carbohydrate extracellular polymeric substances (EPS) and
      soluble microbial product (SMP) were strongly correlated (p<0.01) with organic
      load, salinity and NH4+-N. Exceptionally high beta-glucosidase activities (6700
      10,100Ug-1) were determined during MBR operation with 50% v/v leachate, as a
      result of the low organic carbon availability that extendedly induced beta
      glucosidases to breakdown the least biodegradable organic fraction. Illumina
      sequencing revealed that candidate Saccharibacteria were dominant, independently
      of the leachate concentration applied, whereas other microbiota (21.2% of total
      reads) disappeared when undiluted leachate was used. Fungal taxa shifted from a
      Saccharomyces- to a newly-described Cryptomycota-based community with increasing
      leachate concentration. Indeed, this is the first report on the dominance of
      candidate Saccharibacteria and on the examination of their metabolic behavior in
      a bioreactor treating real wastewater.

PMID- 28432950
TI  - Effects of chlortetracycline and copper on tetracyclines and copper resistance
      genes and microbial community during swine manure anaerobic digestion.
AB  - As antibiotic and heavy metals are over used in the livestock industry, animal
      manure is a reservoir of antibiotic resistance genes (ARGs). Anaerobic digestion
      has been reported to have the potential to reduce ARGs. However, few studies
      investigated whether reduction of ARGs would be affected by different external
      pressures including antibiotics and heavy metals during anaerobic digestion. The
      purpose of this study was thus to investigate effects of both chlortetracycline
      (CTC) and Cu on reduction of ARGs, heavy metal resistance genes (HMRGs) and
      mobile genetic elements (MGEs) during the swine manure anaerobic digestion. The
      results showed that the predominant ARGs (tetO, tetW, tetX, tetL) could be
      effectively reduced (approximately 1.00 log copies/g TS) through mesophilic
      anaerobic digestion. Microbial community evolution was the main driver. It was
      interesting that Treponema might indicate the termination of anaerobic digestion
      and compete with ARGs host bacteria. Addition of CTC, Cu and CTC+Cu affected
      microbial community change and hindered removal of ARGs, especially, CTC+Cu
      seriously affected Treponema and ARGs during anaerobic digestion.

PMID- 28432951
TI  - Microbial communities in the functional areas of a biofilm reactor with anaerobic
      aerobic process for oily wastewater treatment.
AB  - Microbial communities in the functional areas of biofilm reactors with large
      height-diameter ratio using the anaerobic-aerobic (A/O) reflux process was
      investigated to treat heavy oil refinery wastewater without pretreatment. In the
      process, chemical oxygen demand (COD) and total nitrogen (TN) removal reached
      93.2% and 82.8%, and the anaerobic biofilm reactor was responsible for 95% and
      99%, respectively. Areas for hydrolysis acidification and acetic acid production,
      methane production, and COD recovery were obvious in the anaerobic reactor. Among
      all areas, area for hydrolysis acidification and acetic acid production was the
      key factor to improve COD removal efficiency. High throughput sequencing of 16S
      rDNA gene showed that the native community was mainly composed of functional
      groups for hydrocarbon degradation, syntrophic bacteria union body,
      methanogenesis, nitrification, denitrification, and sulfate reduction. The
      deviations between predicted values and actual COD and TN removal were less than
      5% in the optimal prediction model.

PMID- 28432952
TI  - Removal of antibiotics from piggery wastewater by biological aerated filter
      system: Treatment efficiency and biodegradation kinetics.
AB  - This study aimed to investigate the removal efficiency and mechanism for
      antibiotics in swine wastewater by a biological aerated filter system (BAF
      system) in combination with laboratory aerobic and anaerobic incubation
      experiments. Nine antibiotics including sulfamonomethoxine,
      sulfachloropyridazine, sulfamethazine, trimethoprim, norfloxacin, ofloxacin,
      lincomycin, leucomycin and oxytetracycline were detected in the wastewater with
      concentrations up to 192,000ng/L. The results from this pilot study showed
      efficient removals (>82%) of the conventional wastewater pollutants (BOD5, COD,
      TN and NH3-N) and the detected nine antibiotics by the BAF system. Laboratory
      simulation experiment showed first-order dissipation kinetics for the nine
      antibiotics in the wastewater under aerobic and anaerobic conditions. The
      biodegradation kinetic parameters successfully predicted the fate of the nine
      antibiotics in the BAF system. This suggests that biodegradation was the dominant
      process for antibiotic removal in the BAF system.

PMID- 28432953
TI  - New and practical mathematical model of membrane fouling in an aerobic submerged
      membrane bioreactor.
AB  - This study aimed to develop a practical semi-empirical mathematical model of
      membrane fouling that accounts for cake formation on the membrane and its pore
      blocking as the major processes of membrane fouling. In the developed model, the
      concentration of mixed liquor suspended solid is used as a lumped parameter to
      describe the formation of cake layer including the biofilm. The new model
      considers the combined effect of aeration and backwash on the foulants'
      detachment from the membrane. New exponential coefficients are also included in
      the model to describe the exponential increase of transmembrane pressure that
      typically occurs after the initial stage of an MBR operation. The model was
      validated using experimental data obtained from a lab-scale aerobic sponge
      submerged membrane bioreactor (MBR), and the simulation of the model agreed well
      with the experimental findings.

PMID- 28432954
TI  - Fully-automatic left ventricular segmentation from long-axis cardiac cine MR
      scans.
AB  - With an increasing number of large-scale population-based cardiac magnetic
      resonance (CMR) imaging studies being conducted nowadays, there comes the mammoth
      task of image annotation and image analysis. Such population-based studies would
      greatly benefit from automated pipelines, with an efficient CMR image analysis
      workflow. The purpose of this work is to investigate the feasibility of using a
      fully-automatic pipeline to segment the left ventricular endocardium and
      epicardium simultaneously on two orthogonal (vertical and horizontal) long-axis
      cardiac cine MRI scans. The pipeline is based on a multi-atlas-based segmentation
      approach and a spatio-temporal registration approach. The performance of the
      method was assessed by: (i) comparing the automatic segmentations to those
      obtained manually at both the end-diastolic and end-systolic phase, (ii)
      comparing the automatically obtained clinical parameters, including end-diastolic
      volume, end-systolic volume, stroke volume and ejection fraction, with those
      defined manually and (iii) by the accuracy of classifying subjects to the
      appropriate risk category based on the estimated ejection fraction. Automatic
      segmentation of the left ventricular endocardium was achieved with a Dice
      similarity coefficient (DSC) of 0.93 on the end-diastolic phase for both the
      vertical and horizontal long-axis scan; on the end-systolic phase the DSC was
      0.88 and 0.85, respectively. For the epicardium, a DSC of 0.94 and 0.95 was
      obtained on the end-diastolic vertical and horizontal long-axis scans; on the end
      systolic phase the DSC was 0.90 and 0.88, respectively. With respect to the
      clinical volumetric parameters, Pearson correlation coefficient (R) of 0.97 was
      obtained for the end-diastolic volume, 0.95 for end-systolic volume, 0.87 for
      stroke volume and 0.84 for ejection fraction. Risk category classification based
      on ejection fraction showed that 80% of the subjects were assigned to the correct
      risk category and only one subject (< 1%) was more than one risk category off. We
      conclude that the proposed automatic pipeline presents a viable and cost
      effective alternative for manual annotation.

PMID- 28432955
TI  - The calorimetric properties of liposomes determine the morphology of dried
      droplets.
AB  - The evaporation of liquid droplets deposited on a substrate is a very complex
      phenomenon. Driven by capillary and Marangoni flows, particle-particle and
      particle-substrate interactions, the deposits they leave are vestiges of such
      complexity. We study the formation of patterns during the evaporation of liposome
      suspension droplets deposited on a hydrophobic substrate at different
      temperatures. We observed that as we change the temperature of the substrate, a
      morphological phase transition occurs at a given temperature Tm. This temperature
      corresponds to the gel-fluid lipid melting transition of the liposome suspension.
      Optical microscopy and atomic force microscopy are used to study the morphology
      of the patterns. Based on the radial density profiles we found that all
      structures can be classified into two groups: patterns composed by nearly uniform
      deposition (below Tm) and prominent structures containing randomly distributed
      voids (above Tm).

PMID- 28432956
TI  - Introduction of N-cadherin-binding motif to alginate hydrogels for controlled
      stem cell differentiation.
AB  - Control of stem cell fate and phenotype using biomimetic synthetic extracellular
      matrices (ECMs) is an important tissue engineering approach. Many studies have
      focused on improving cell-matrix interactions. However, proper control of cell
      cell interactions using synthetic ECMs could be critical for tissue engineering,
      especially with undifferentiated stem cells. In this study, alginate hydrogels
      were modified with a peptide derived from the low-density lipoprotein receptor
      related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell
      interaction motif. In vitro changes in the morphology and differentiation of
      mouse bone marrow stromal cells (D1 stem cells) cultured in LRP5-alginate
      hydrogels were investigated. LRP5-alginate gels successfully induced stem cell
      aggregation and enhanced chondrogenic differentiation of D1 stem cells, compared
      to RGD-alginate gels, at low cell density. This approach to tailoring synthetic
      biomimetic ECMs using cell-cell interaction motifs may be critical in tissue
      engineering approaches using stem cells.

PMID- 28432957
TI  - Nanoencapsulation strategies for the delivery of novel bifunctional
      antioxidant/sigma1 selective ligands.
AB  - Nowadays sigma-1 receptors are considered as new therapeutic objectives for
      central nervous system neurodegenerative diseases. Among different molecules,
      alpha lipoic acid has been identified as a natural potent antioxidant drug, whose
      therapeutic efficacy is limited by its many drawbacks, such as fast metabolism,
      poor bioavailability and high physico-chemical instability. Alfa-lipoic acid
      derivatives have been recently developed demonstrating their neuroprotective
      activity and effectiveness in different types of oxidative stress. In this work,
      two derivatives containing an amide or an ester functional group with different
      lipophilicity, were selected for their important affinity for sigma-1 receptors.
      Herein, in order to improve the in vitro stability and antioxidant effectiveness
      of alpha-lipoic acid derivatives, we focused our efforts in the nanoencapsulation
      strategies. Aqueous-core nanocapsules for the delivery of the hydrophilic
      compound and nanostructured lipid carrier for the lipophilic derivative, were
      properly designed and prepared using a direct or inverse eco-friendly organic
      solvent-free procedure. All nanosystems were characterized in terms of mean size,
      polydispersity, stability, morphology, encapsulation efficiency and in vitro
      release profiles. In order to evaluate the nanocarriers biocompatibility and
      antioxidant effectiveness, in vitro biological studies (cell viability, total
      antioxidant capacity and total oxidative status) were developed on primary human
      whole blood cell cultures, on both unloaded and derivatives-loaded nanodevices.

PMID- 28432958
TI  - Membrane fusion between baculovirus budded virus-enveloped particles and giant
      liposomes generated using a droplet-transfer method for the incorporation of
      recombinant membrane proteins.
AB  - Giant proteoliposomes are generally useful as artificial cell membranes in
      biochemical and biophysical studies, and various procedures for their preparation
      have been reported. We present here a novel preparation technique that involves
      the combination of i) cell-sized lipid vesicles (giant unilamellar vesicles,
      GUVs) that are generated using the droplet-transfer method, where lipid monolayer
      coated water-in-oil microemulsion droplets interact with oil/water interfaces to
      form enclosed bilayer vesicles, and ii) budded viruses (BVs) of baculovirus
      (Autographa californica nucleopolyhedrovirus) that express recombinant
      transmembrane proteins on their envelopes. GP64, a fusogenic glycoprotein on
      viral envelopes, is activated by weak acids and is thought to cause membrane
      fusion with liposomes. Using confocal laser scanning microscopy (CLSM), we
      observed that the single giant liposomes fused with octadecyl rhodamine B
      chloride (R18)-labeled wild-type BV envelopes with moderate leakage of entrapped
      soluble compounds (calcein), and the fusion profile depended on the pH of the
      exterior solution: membrane fusion occurred at pH ~4-5. We further demonstrated
      that recombinant transmembrane proteins, a red fluorescent protein (RFP)-tagged
      GPCR (corticotropin-releasing hormone receptor 1, CRHR1) and envelope protein
      GP64 could be partly incorporated into membranes of the individual giant
      liposomes with a reduction of the pH value, though there were also some immobile
      fluorescent spots observed on their circumferences. This combination may be
      useful for preparing giant proteoliposomes containing the desired membranes and
      inner phases.

PMID- 28432959
TI  - Molecular dynamics simulation studies of novel beta-lactamase inhibitor.
AB  - New Delhi Metallo-beta-Lactamase-1 (NDM-1) has drawn great attention due to its
      diverse antibiotic resistant activity. It can hydrolyze almost all clinically
      available beta-lactam antibiotics. To inhibit the activity of NDM-1 a new
      strategy is proposed using computational methods. Molecular dynamics (MD)
      simulations are used to analyze the molecular interactions between selected
      inhibitor candidates and NDM-1 structure. The enzyme-ligand complex is subject to
      binding free energy calculations using MM(PB/GB)SA methods. The role of each
      residue of the active site contributing in ligand binding affinity is explored
      using energy decomposition analysis. Furthermore, a hydrogen bonding network
      between ligand and enzyme active site is observed and key residues are identified
      ensuring that the ligand stays inside the active site and maintains its movement
      towards the active site pocket. A production run of 150ns is carried out and
      results are analyzed using root mean square deviation (RMSD), root mean square
      fluctuation (RMSF), and radius of gyration (Rg) to explain the stability of
      enzyme ligand complex. Important active site residue e.g. PHE70, VAL73, TRP93,
      HIS122, GLN123, ASP124, HIS189, LYS216, CYS208, LYS211, ALA215, HIS250, and
      SER251 were observed to be involved in ligand attachemet inside the active site
      pocket, hence depicting its inhibitor potential. Hydrogen bonds involved in
      structural stability are analyzed through radial distribution function (RDF) and
      contribution of important residues involved in ligand movement is explained using
      a novel analytical tool, axial frequency distribution (AFD) to observe the role
      of important hydrogen bonding partners between ligand atoms and active site
      residues.

PMID- 28432960
TI  - Molecular dynamic simulations on TKX-50/RDX cocrystal.
AB  - Dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) is a newly synthesized
      energetic material with excellent comprehensive properties.
      Cyclotrimethylenetrinitramine (RDX) is currently one of the most widely used
      energetic materials in the world. TKX-50 and RDX supercell models and TKX-50/RDX
      cocrystal model were constructed based on their crystal cell parameters and the
      formation mechanism of cocrystal, respectively, then they were simulated by
      molecular dynamics (MD) simulations. The maximum trigger bond (NNO2)
      length(Lmax), binding energy (Ebind), radial distribution function (RDF),
      cohesive energy density(CED) and mechanical properties were simulated at
      different temperatures based on the simulated equilibrium structures of the
      models. The simulated results indicate that hydrogen bond and van der Waals force
      interactions exist in the cocrystal system and the hydrogen bonds are mainly
      derived from the hydrogen atom of TKX-50 with the oxygen or nitrogen atom of RDX.
      Moreover, TKX-50/RDX cocrystal structure significantly reduces the sensitivity
      and improves the thermodynamic stability of RDX, and it also shows better
      mechanical properties than pure TKX-50 and RDX, indicating that it will vastly
      expand the application scope of the single compound explosives.

PMID- 28432961
TI  - Diurnal patterns and relationships between physiological and self-reported stress
      in patients with epilepsy and psychogenic non-epileptic seizures.
AB  - PURPOSE: Patients with epilepsy and those with psychogenic non-epileptic seizures
      (PNES) experience high levels of stress and stress is one of the most frequently
      self-identified seizure precipitants. Although stress is a multifaceted
      phenomenon, few studies have systematically examined its different components in
      patients with seizures. The aim of this study was therefore to describe diurnal
      patterns of psychological and physiological measures of stress in patients with
      epilepsy and patients with PNES, and explore their relationships to each other in
      order to improve our understanding of the mechanisms underlying stress and
      seizure occurrence in these patients. METHOD: A range of stress markers including
      self-reported stress, salivary cortisol, and heart rate variability (HRV) were
      explored in adult patients with refractory epilepsy (N=22) and those with PNES
      (N=23) undergoing three- to five-day video-telemetry. RESULTS: A diurnal pattern
      was observed in the physiological measures, characterized by higher levels of
      physiological arousal in the mornings and lower levels at night in both patients
      with epilepsy and PNES. The physiological measures (cortisol and HRV) were
      associated with each other in patients with epilepsy; no close relationship was
      found with self-reported stress in either of the two patient groups. CONCLUSION:
      The findings contribute to and expand on previous studies of the patterns of
      stress in patients with seizures. The results also indicate a discrepancy between
      patients' physiological responses and their subjective stress perceptions,
      suggesting that simple self-reports cannot be used as a proxy of physiological
      arousal in patients with seizures and stress. Stress in these patient groups
      should be studied using a combination of complementary measures.

PMID- 28432962
TI  - GC-MS quantitative analysis of black market pharmaceutical products containing
      anabolic androgenic steroids seized by the Brazilian Federal Police.
AB  - The use of counterfeit or substandard medicines can have an important health
      impact, resulting in therapeutic failure, be toxic or even cause death. Anabolic
      steroids are a frequent target for counterfeiters worldwide, being the second
      most frequent counterfeited class in Brazil. The aims of this work were to
      optimize and validate a GC-MS method for the quantitative determination of
      anabolic steroids in tablet, aqueous suspension and oil solution forms, and to
      analyze pharmaceutical products sent to Brazilian Federal Police (BFP) for
      forensic analysis. Sample preparation included extraction with methanol in
      ultrasonic bath followed by centrifugation. The method was successfully validated
      and 345 samples of pharmaceutical products were analyzed (328 medicines and 17
      dietary supplements). About 42% of the medicines were counterfeits, 28.7% of
      tablets, 12.0% of suspensions and 65.2% of oil solutions; 11% were considered
      substandards. Five dietary supplements contained undeclared anabolic steroids,
      including two containing methandrostenolone at 5.4 and 5.8mg/capsule, equivalent
      to levels found in medicines. The proposed method is suitable for implementation
      in routine analysis for identification of counterfeits and substandard products.
      The analytical results show the need to raise awareness of consumers over the
      risks from the consumption of anabolic steroids from the clandestine market and
      for more incisive actions from government agencies aiming at decreasing the
      availability of these products.

PMID- 28432963
TI  - Health hazards of child labor in the leather products and surgical instrument
      manufacturing industries of Sialkot, Pakistan.
AB  - Child labor is a major challenge in the developing countries and comprehensive
      health hazard identification studies on this issue are still lacking. Therefore,
      the current study is an effort to highlight the health concerns of child labor
      exposed in the key small scale industries of Sialkot, Pakistan. Our findings
      revealed jolting levels of heavy metals in the urine, blood, serum, saliva, and
      hair samples collected from the exposed children. For example, in the urine
      samples, Cd, Cr, Ni, and Pb were measured at the respective concentrations of
      39.17, 62.02, 11.94 and 10.53 MUg/L in the surgical industries, and 2.10, 4.41,
      1.04 and 5.35 MUg/L in the leather industries. In addition, source apportionment
      revealed polishing, cutting, and welding sections in the surgical industries and
      surface coating, crusting, and stitching sections in the leather industries were
      the highest contributors of heavy metals in the bio-matrices of the exposed
      children, implying the dusty, unhygienic, and unhealthy indoor working
      conditions. Further, among all the bio-matrices, the hair samples expressed the
      highest bioaccumulation factor for heavy metals. In accordance with the heavy
      metal levels reported in the exposed children, higher oxidative stress was found
      in the children working in the surgical industries than those from the leather
      industries. Moreover, among heavy metals' exposure pathways, inhalation of
      industrial dust was identified as the primary route of exposure followed by the
      ingestion and dermal contact. Consequently, chemical daily intake (CDI),
      carcinogenic and non-carcinogenic hazard quotients (HQs) of heavy metals were
      also reported higher in the exposed children and were also alarmingly higher than
      the corresponding US EPA threshold limits. Taken all together, children were
      facing serious health implications in these industries and need immediate
      protective measures to remediate the current situation.

PMID- 28432964
TI  - Phytate induced arsenic uptake and plant growth in arsenic-hyperaccumulator
      Pteris vittata.
AB  - Phytate is abundant in soils, which is stable and unavailable for plant uptake.
      However, it occurs in root exudates of As-hyperaccumulator Pteris vittata (PV).
      To elucidate its effect on As uptake and growth, P. vittata were grown on agar
      media (63 MUM P) containing 50 MUM As and/or 50 or 500 MUM phytate with non As
      hyperaccumulator Pteris ensiformis (PE) as a congeneric control for 60 d. Phytate
      induced efficient As and P uptake, and enhanced growth in PV, but had little
      effects on PE. The As concentrations in PV fronds and roots were 157 and 31 mg kg
      1 in As50+phytate50, 2.2- and 3.1-fold that of As50 treatment. Phosphorus uptake
      by PV was reduced by 27% in As treatment than the control (P vs. P+As) but
      increased by 73% comparing phytate500 to phytate500+As, indicating that PV
      effectively took up P from phytate. Neither As nor phytate affected Fe
      accumulation in PV, but phytate reduced root Fe concentration in PE (46-56%). As
      such, the increased As and P and the unsuppressed Fe uptake in PV probably
      promoted PV growth. Thus, supplying phytate to As-contaminated soils may promote
      As uptake and growth in PV and its phytoremediation ability.

PMID- 28432965
TI  - Spatiotemporal description of BTEX volatile organic compounds in a Middle Eastern
      megacity: Tehran Study of Exposure Prediction for Environmental Health Research
      (Tehran SEPEHR).
AB  - The spatiotemporal variability of ambient volatile organic compounds (VOCs) in
      Tehran, Iran, is not well understood. Here we present the design, methods, and
      results of the Tehran Study of Exposure Prediction for Environmental Health
      Research (Tehran SEPEHR) on ambient concentrations of benzene, toluene,
      ethylbenzene, p-xylene, m-xylene, o-xylene (BTEX), and total BTEX. To date, this
      is the largest study of its kind in a low- and middle-income country and one of
      the largest globally. We measured BTEX concentrations at five reference sites and
      174 distributed sites identified by a cluster analytic method. Samples were taken
      over 25 consecutive 2-weeks at five reference sites (to be used for temporal
      adjustments) and over three 2-week campaigns in summer, winter, and spring at 174
      distributed sites. The annual median (25th-75th percentile) for benzene, the most
      carcinogenic of the BTEX species, was 7.8 (6.3-9.9) MUg/m3, and was higher than
      the national and European Union air quality standard of 5 MUg/m3 at approximately
      90% of the measured sites. The estimated annual mean concentrations of BTEX were
      spatially highly correlated for all pollutants (Spearman rank coefficient 0.81
      0.98). In general, concentrations and spatial variability were highest during the
      summer months, most likely due to fuel evaporation in hot weather. The annual
      median of benzene and total BTEX across the 35 sites in the Tehran regulatory
      monitoring network (7.7 and 56.8 MUg/m3, respectively) did a reasonable job of
      approximating the additional 144 city-wide sites (7.9 and 58.7 MUg/m3,
      respectively). The annual median concentrations of benzene and total BTEX within
      300 m of gas stations were 9.1 and 67.3 MUg/m3, respectively, and were higher
      than sites outside this buffer. We further found that airport did not affect
      annual BTEX concentrations of sites within 1 km. Overall, the observed ambient
      concentrations of toxic VOCs are a public health concern in Tehran.

PMID- 28432966
TI  - Risk for eating disorders modulates interpretation bias in a semantic priming
      task.
AB  - The current study used a semantic priming paradigm to investigate the presence of
      implicit interpretation biases for food and body shape words among 118
      undergraduate females. Reaction times (RTs) were recorded while participants made
      lexical decisions (i.e., word vs. non-word judgments) to lexical targets that
      were preceded by negatively valenced eating disorder related (e.g., fat-PIZZA),
      eating disorder unrelated (e.g., party-PIZZA), or semantically unrelated (e.g.,
      umbrella-PIZZA) prime words. Self-reported eating disorder traits were assessed
      using the Body Shape Questionnaire (BSQ-34), the Eating Attitudes Test (EAT-26),
      and the Eating Disorder Examination (EDE-Q 6.0). Results suggested that biased RT
      priming effects for eating disorder related word pairs were strongly associated
      with measures of body dissatisfaction and ED symptomology. Specifically, scales
      targeting eating disordered cognitions (the BSQ-34 and the Shape/Weight Concern
      subscales of the EDE-Q 6.0) demonstrated the strongest association with implicit
      interpretation biases as assessed by performance on the semantic priming task.

PMID- 28432967
TI  - Friendliness, functionality and freedom: Design characteristics that support
      midwifery practice in the hospital setting.
AB  - OBJECTIVE: to identify and describe the design characteristics of hospital birth
      rooms that support midwives and their practice. DESIGN: this study used a
      qualitative exploratory descriptive methodology underpinned by the theoretical
      approach of critical realism. Data was collected through 21 in-depth, face-to
      face photo-elicitation interviews and a thematic analysis guided by study
      objectives and the aims of exploratory research was undertaken. SETTING: the
      study was set at a recently renovated tertiary hospital in a large Australian
      city. PARTICIPANTS: participants were 16 registered midwives working in a
      tertiary hospital; seven in delivery suite and nine in birth centre settings.
      Experience as a midwife ranged from three to 39 years and the sample included
      midwives in diverse roles such as educator, student support and unit manager.
      FINDINGS: three design characteristics were identified that supported midwifery
      practice. They were friendliness, functionality and freedom. Friendly rooms
      reduced stress and increased midwives' feelings of safety. Functional rooms
      enabled choice and provided options to better meet the needs of labouring women.
      And freedom allowed for flexible, spontaneous and responsive midwifery practice.
      CONCLUSION: hospital birth rooms that possess the characteristics of
      friendliness, functionality and freedom offer enhanced support for midwives and
      may therefore increase effective care provision. IMPLICATIONS FOR PRACTICE: new
      and existing birth rooms can be designed or adapted to better support the
      wellbeing and effectiveness of midwives and may thereby enhance the quality of
      midwifery care delivered in the hospital. Quality midwifery care is associated
      with positive outcomes and experiences for labouring women. Further research is
      required to investigate the benefit that may be transmitted to women by
      implementing design intended to support and enhance midwifery practice.

PMID- 28432968
TI  - Applicability of light sources and the inner filter effect in UV/acetylacetone
      and UV/H2O2 processes.
AB  - Light source is a crucial factor in the application of a photochemical process,
      which determines the energy efficiency. The performances of acetylacetone (AA) in
      conversion of aqueous contaminants under irradiation with a low-pressure mercury
      lamp, a medium-pressure mercury lamp, a xenon lamp, and natural sunlight were
      investigated and compared with those of H2O2 as reference. In all cases, AA was
      superior to H2O2 in the degradation of Acid Orange 7. Using combinations of the
      different light sources with various cut-off and band-pass filters, the spectra
      responses of the absorbed photons in the UV/AA and UV/H2O2 processes were
      determined for two colored and two colorless compounds. The photonic efficiency
      (phi) of the two photochemical processes was found to be target-dependent. A
      calculation approach for the inner filter effect was developed by taking the
      obtained phi into account, which provides a more accurate indication of the
      reaction mechanisms.

PMID- 28432969
TI  - Quantitative effects of amination degree on the magnetic iron oxide nanoparticles
      (MIONPs) using as adsorbents to remove aqueous heavy metal ions.
AB  - The hierarchical effect of amine-functionalization on nanoparticle properties,
      magnetism especially, and adsorption of Cu2+, Ni2+, Pb2+ and Zn2+ by aminated
      MIONPs were investigated elaboratively. The results reflected that the
      dispersibility and stability of nanoparticles in aqueous solution were both
      enhanced as MIONPs grafted with amine groups, while saturation magnetism and
      magnetic recovery conveniences had a negatively correlative relation with the
      amination degree. In addition, the adsorption performances of Cu2+, Ni2+, Pb2+
      and Zn2+ by different aminated MIONPs were also studied comprehensively. The
      results showed that the initial adsorption rates and adsorption capacities of
      heavy metal ions increased with the amination degree. In addition, the
      quantitative correlation between amination degree and adsorption capacities of
      different heavy metal ions could be described well by a model built on basis of
      adsorption processes.

PMID- 28432970
TI  - Insights into key factors controlling GO stability in natural surface waters.
AB  - The effects of pH, cations (Na+, K+, Mg2+, Ca2+ and Al3+), and anions (Cl-, HCO3
      , HPO42- and SO42-) on graphene oxide (GO) stability were investigated to address
      the current limitations in the knowledge regarding the stability of GO in natural
      surface water and its underlying mechanism. The threshold values of cations that
      destabilize GO were obtained and affected by both pH and anions. By employing
      elemental mapping and studying the effects of polyacrylic acid (PAA) on GO
      sedimentation and the re-dispersion of GO aggregates, we find that the GO
      aggregates induced by Na+ and K+ via electric double layer suppression and by
      Ca2+ and Al3+ via strong complxing are difficult to re-disperse completely.
      Specifically, more PAA is needed to re-disperse GO aggregates than to stabilize
      GO, which suggests that after GO binds with heavy metal ions. It is less likely
      to be transported over a long distance even in natural water that are rich in
      natural organic matter. Finally, we find that the key factor controlling GO
      sedimentation in natural surface waters is its binding with Mg2+ and Ca2+. This
      study is expected to provide critical knowledge to more accurately predict the
      fate of GO in natural surface aquatic environments.

PMID- 28432971
TI  - Voids padding induced further enhancement in photocatalytic performance of porous
      graphene-like carbon nitride.
AB  - Design of 2-Dimensional nanostructured photocatalyst is an effective way to
      improve the photocatalytic activity of its bulk counterpart. However, the
      remaining (or newborn) drawbacks, such as enlarged band gap and the surface
      recombination of photogenerated charge carries, extremely limited the practical
      application of nanosheeted photocatalysts in solar energy conversion. In this
      study, we demonstrated that the voids padding with NH4Cl can eliminate part of
      quantum size effect to reduce the band gap of nanosheeted carbon nitride. In
      addition, the padded NH4Cl can create conjugate center and interface electric
      field in nanosheeted carbon nitride, and therefore to inhibit the surface
      recombination of photogenerated charge carries. This work not only provides a
      facile strategy to eliminate the drawbacks of nanosheeted carbon nitride, but
      also paves a new way to further improve the photocatalytic activity of other nano
      sheeted materials.

PMID- 28432972
TI  - Assessment of the bioavailability and depuration of uranium, cesium and thorium
      in snails (Cantareus aspersus) using kinetics models.
AB  - Uranium ore waste has led to soil contamination that may affect both
      environmental and soil health. To analyze the risk of metal transfer, metal
      bioavailability must be estimated by measuring biological parameters. Kinetic
      studies allow taking into account the dynamic mechanisms of bioavailability, as
      well as the steady state concentration in organisms necessary to take into
      account for relevant risk assessment. In this way, this work aims to model the
      snail accumulation and excretion kinetics of uranium (U), cesium (Cs) and thorium
      (Th). Results indicate an absence of Cs and Th accumulation showing the low
      bioavailability of these two elements and a strong uranium accumulation in snails
      related to the levels of soil contamination. During the depuration phase, most of
      the uranium ingested was excreted by the snails. After removing the source of
      uranium by soil remediation, continued snails excretion of accumulated uranium
      would lead to the return of their initial internal concentration, thus the
      potential trophic transfer of this hazardous element would stop.

PMID- 28432973
TI  - Methane explosion suppression characteristics based on the NaHCO3/red-mud
      composite powders with core-shell structure.
AB  - The NaHCO3/red-mud (RM) composite powders were successfully prepared by the
      solvent-anti-solvent method for methane explosion suppression. The RM was used as
      a carrier, and the NaHCO3 was used as a loaded inhibitor. The NaHCO3/RM composite
      powders showed a special core-shell structure and excellent endothermic
      performance. The suppression properties of NaHCO3/RM composite for 9.5% CH4
      explosion were tested in a 20L spherical explosion vessel and a 5L Perspex duct.
      The results showed that the NaHCO3/RM composite powders displayed a much better
      suppression property than the pure RM or NaHCO3 powders. The loading amount of
      NaHCO3 has an intensive influence on the inhibition property of NaHCO3/RM
      composite powders. The best loaded content of NaHCO3 is 35%. It exhibited
      significant inhibitory effect that the explosion max-pressure declined 44.9%, the
      max-pressure rise rate declined 96.3% and the pressure peak time delayed 366.7%,
      respectively.

PMID- 28432974
TI  - Highly efficient degradation of thidiazuron with Ag/AgCl- activated carbon
      composites under LED light irradiation.
AB  - Thidiazuron (TDZ; 1-phenyl-3-(1,2,3-thiadiazol-5-yl)urea) is one of the most
      widely used defoliant and easy to dissolve in surface water. Risk associated with
      the pesticide is not clearly defined, so it is important to remove/degrade TDZ
      with an efficient and environment friendly technology. Here, we investigated the
      use of Ag/AgCl-activated carbon (Ag/AgCl-AC) composites in photocatalytic
      degradation of TDZ under LED light. By the synergic effect of Ag/AgCl and AC, the
      optimum Ag/carbon weight ratio of 2:1 exhibited superior visible-light
      photocatalytic activity, the highest removal efficiency was close to 91% in pH 7
      matrix. Different types of Ag/AgCl-AC composites were tested, all showed much
      faster photodegradation kinetics than bare Ag/AgCl in 210min. The degradation
      products as identified by HPLC-MS revealed that the hydroxylation by hydroxyl
      radicals and that of oxidation by superoxide radicals as well as holes were the
      two main pathways for TDZ degradation. Results revealed that the adsorption
      concentrated TDZ molecules and the photocatalytically generated radicals rapidly
      degradated TDZ, the two contributions functioned together for removal of the
      pollutant from water.

PMID- 28432976
TI  - Cuticular wax coverage and composition differ among organs of Taraxacum
      officinale.
AB  - Primary plant surfaces are coated with hydrophobic cuticular waxes to minimize
      non-stomatal water loss. Wax compositions differ greatly between plant species
      and, in the few species studied systematically so far, also between organs,
      tissues, and developmental stages. However, the wax mixtures of more species in
      diverse plant families must be investigated to assess overall wax variability,
      and ultimately to correlate organ-specific composition with local water barrier
      properties. Here, we present comprehensive analyses of the waxes covering five
      organs of Taraxacum officinale (dandelion), to help close a gap in our
      understanding of wax chemistry in the Asteraceae family. First, novel wax
      constituents of the petal wax were identified as C25 6,8- and 8,10-ketols as well
      as C27 6,8- and 8,10-ketols. Nine other component classes (fatty acids, primary
      alcohols, esters, aldehydes, alkanes, triterpenols, triterpene acetates, sterols,
      and tocopherols) were detected in the wax mixtures covering leaves, peduncles,
      and petals, as well as fruit beaks and pappi. Wax coverages varied from 5 MUg/cm2
      on peduncles to 37 MUg/cm2 on petals. Alcohols predominated in leaf wax, while
      both alcohols and alkanes were found in similar amounts on peduncles and petals,
      and mainly alkanes on the fruit beaks and pappi. Chain length distributions
      within the wax compound classes were similar between organs, centered around C26
      for fatty acids, alcohols, and aldehydes, and C29 for alkanes. However, the
      quantities of homologs with longer chain lengths varied substantially between
      organs, reaching well beyond C30 on all surfaces except leaves, suggesting
      differences in elongation enzymes determining the alkyl chain structures. The
      detailed wax profiles presented here will serve as basis for future
      investigations into wax biosynthesis in the Asteraceae and into wax functions on
      different dandelion organs.

PMID- 28432977
TI  - Effect of short-term Zn/Pb or long-term multi-metal stress on physiological and
      morphological parameters of metallicolous and nonmetallicolous Echium vulgare L.
      populations.
AB  - The aim of the study was to determine the response of metallicolous and
      nonmetallicolous Echium vulgare L. populations to chronic multi-metal (Zn, Pb,
      Cd) and acute Zn (200, 400 MUM) and Pb (30, 60 MUM) stress. Three populations of
      E. vulgare, one from uncontaminated and two from metal-contaminated areas, were
      studied. Two types of experiments were performed - a short-term hydroponic
      experiment with acute Zn or Pb stress and a long-term manipulative soil
      experiment with the use of soils from the sites of origin of the three
      populations. Growth parameters, such as shoot and root fresh weight and leaf
      area, as well as organic acid accumulation were determined. Moreover, the
      concentration of selected secondary metabolites and antioxidant capacity in the
      three populations exposed to Pb or Zn excess were measured. Both metallicolous
      populations generally achieved higher biomass compared with the nonmetallicolous
      population cultivated under metal stress in hydroponics or on metalliferous
      substrates. Plants exposed to Pb or Zn excess or contaminated soil substrate
      exhibited higher malate and citrate concentrations compared with the reference
      (no metal stress) plants. It was observed that Zn or Pb stress increased
      accumulation of allantoin, chlorogenic and rosmarinic acids, total phenolics, and
      flavonoids. Moreover, it was shown that Pb sequestration in the roots or Zn
      translocation to the shoots may play a role in enhanced metal tolerance of
      metallicolous populations under acute Pb/Zn stress.

PMID- 28432975
TI  - Vaccination strategies against Zika virus.
AB  - The epidemic emergence of Zika virus (ZIKV) in 2015-2016 has been associated with
      congenital malformations and neurological sequela. Current efforts to develop a
      ZIKV vaccine build on technologies that successfully reduced infection or disease
      burden against closely related flaviviruses or other RNA viruses. Subunit-based
      (DNA plasmid and modified mRNA), viral vectored (adeno- and measles viruses) and
      inactivated viral vaccines are already advancing to clinical trials in humans
      after successful mouse and non-human primate studies. Among the greatest
      challenges for the rapid implementation of immunogenic and protective ZIKV
      vaccines will be addressing the potential for exacerbating Dengue virus infection
      or causing Guillain-Barre syndrome through production of cross-reactive immunity
      targeting related viral or host proteins. Here, we review vaccine strategies
      under development for ZIKV and the issues surrounding their usage.

PMID- 28432978
TI  - Cadmium hampers salt tolerance of Sesuvium portulacastrum.
AB  - It is well known that salinity reduces cadmium toxicity in halophytes. However,
      the possible interference of Cd with the mechanisms of salt tolerance is poorly
      explored. The aim of this study was to see whether Cd affects salt tolerance
      mechanisms in the halophyte Sesuvium portulacastrum. S. portulacastrum plants
      obtained from cuttings were grown in hydroponics for 3 weeks and then exposed to
      low (0.09 mM) or moderate (200 mM) NaCl concentrations, alone or in combination
      with 25 MUM CdCl2. Microscopy observation revealed two strategies of salt
      tolerance: euhalophytism and secretion of salt by bladder cells. Cadmium exposure
      hardly influenced the total leaf Na+ concentrations. However, Cd supply delayed
      the salt-induced upregulation of AHA1 (plasma membrane H+-ATPase 1) and SOS1
      (plasma membrane Na+ transporter "Salt Overly Sensitive 1"), genes that are
      essential for salt tolerance. Moreover, Cd induced the activation of BADH, coding
      for betaine aldehyde dehydrogenase, indicating enhanced osmotic stress due to Cd.
      Sodium-green fluorescence in protoplasts from plants grown with low or high NaCl,
      alone or in combination with Cd, revealed higher Na+ concentrations in the
      cytoplasm of Cd-exposed plants. Taken together the results indicate interference
      of Cd with salt tolerance mechanisms in S. portulacastrum. This may have
      consequences for the efficient use of halophytes in phytoremediation of Cd
      contaminated saline soils.

PMID- 28432979
TI  - The reality of economics for oncologists.
AB  - This article outlines the historical development of health economics and its
      present role in oncology related health technology assessments (HTAs). Despite
      concerns about the prices and immediate costs of new anticancer medicines for
      indications such as breast cancer overall spending on such treatments is
      affordable and offers long term value for money in countries such as the US,
      Canada and those of Western Europe. Oncologists wishing to protect the interests
      of current and future patients with both advanced and earlier stage cancers may
      be regarded as having a responsibility to understand the nature of health
      economic evaluations, and to be actively involved in decisions affecting access
      to current treatments and future levels of investment in incrementally improving
      therapies.

PMID- 28432980
TI  - Discovery of potential inhibitor against human acetylcholinesterase: a molecular
      docking and molecular dynamics investigation.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease of central
      nervous system among elderly people. Human acetylcholinesterase (hAChE), an
      important enzyme in neuronal signaling, is responsible for the degradation of
      acetylcholine which in turn prevents the post synaptic signal transmissions.
      hAChE has been an attractive target of drug discovery for the search of
      therapeutics against AD. In the recent past hAChE has become hot target for the
      investigation of new potential therapeutics. We performed virtual screening of
      entire database against hAChE. Further, the extra precision molecular docking was
      carried out to refine the docking results and the best complex was passed for
      molecular dynamics simulations in order of understanding the hAChE dynamics and
      its behavior in complex with the ligand which corroborate the outcomes of virtual
      screening. This also provides binding free energy data that establishes the
      ligands efficiency for inhibiting hAChE. The computational findings discussed in
      this paper provide initial information of inhibitory effects of ligand, (drugbank
      entry DB00983), over hAChE.

PMID- 28432981
TI  - Hidden Markov model and Chapman Kolmogrov for protein structures prediction from
      images.
AB  - Protein structure prediction and analysis are more significant for living organs
      to perfect asses the living organ functionalities. Several protein structure
      prediction methods use neural network (NN). However, the Hidden Markov model is
      more interpretable and effective for more biological data analysis compared to
      the NN. It employs statistical data analysis to enhance the prediction accuracy.
      The current work proposed a protein prediction approach from protein images based
      on Hidden Markov Model and Chapman Kolmogrov equation. Initially, a preprocessing
      stage was applied for protein images' binarization using Otsu technique in order
      to convert the protein image into binary matrix. Subsequently, two counting
      algorithms, namely the Flood fill and Warshall are employed to classify the
      protein structures. Finally, Hidden Markov model and Chapman Kolmogrov equation
      are applied on the classified structures for predicting the protein structure.
      The execution time and algorithmic performances are measured to evaluate the
      primary, secondary and tertiary protein structure prediction.

PMID- 28432982
TI  - Demyelinating polyradiculoneuropathy under combined BRAF/MEK inhibitors.

PMID- 28432983
TI  - Improved resolution and simplification of the spin-diffusion-based NMR method for
      the structural analysis of mixed-linker MOFs.
AB  - Nuclear magnetic resonance spectroscopy combined with modeling represents a
      powerful tool for the structural analysis of heterogeneous materials. In this
      contribution we describe an upgraded method, particularly suited for the
      structural analysis of mixed-linker metal-organic framework materials, which is
      based on the measurement and modeling of proton spin diffusion among
      constituents. We tested the method on a UiO-66-type metal-organic material, in
      which the organic building units were 1,4-benzenedicarboxylate and trans-1,4
      cyclohexanedicarboxylate anions distributed within the framework in an unknown
      manner. We showed that resolution of the signals of different building units
      could be significantly enhanced by the carbon-detected version of the proton spin
      diffusion measurement. Because this kind of measurement is much more time
      consuming than the proton-detected measurement and because one has to carry out
      several two-dimensional measurements to extract spin-diffusion curves, we
      inspected the possibility of reducing the number of such measurements. This could
      be done by limiting the analysis to short mixing times, for which, as shown in
      this contribution, linear approximation is valid. When working in the linear
      regime, only a few experimental points are needed to determine the slope of spin
      diffusion curves. Usage of short spin-diffusion mixing times significantly
      shortened the total measurement time and also markedly simplified the modeling of
      spin-diffusion curves.

PMID- 28432985
TI  - LIF endometrial expression is impaired in women with unexplained infertility
      while LIF-R expression in all infertility sub-groups.
AB  - The main objective of our study was to study LIF and LIF-R endometrial expression
      during the implantation window in the various sub-groups of infertile women
      according to infertility cause. A prospective observational case-control study
      was performed from March 2013 to February 2016. Infertile women consisted of the
      patients' group (group 2) while fertile women were the control group (group 1).
      Infertile women were divided according to infertility cause in women with tubal
      factor (group 2a), poor ovarian reserve (group 2b), endometriosis (group 2c) and
      unexplained infertility (group 2d). Endometrial biopsy was performed on 7th-8th
      postovulatory menstrual day. Leukemia Inhibitory Factor (LIF) and LIF-Receptor
      (LIF-R) expression in epithelial and stromal cells were assessed with
      Immunohistochemistry (IHC). There were 20 infertile with poor ovarian reserve, 15
      with tubal factor, 10 with endometriosis and 15 with unexplained infertility
      included in the analysis. LIF expression in patients with unexplained infertility
      was significantly compared with controls (P=0.006). No significant difference was
      observed between patients with tubal factor, poor ovarian reserve and
      endometriosis compared with control group (P=0.78, P=0.44 and P=0.56
      respectively). Analysis of LIF-R expression in sub-categories of infertility
      indicated that expression was significantly decreased in all sub-groups of
      infertility. Our study indicated impaired LIF expression levels only in women
      with unexplained infertility, while LIF-R expression was impaired in all sub
      groups of infertile women. Further multicenter prospective studies should be
      performed in order to assess the exact etiopathogenetic role of these cytokines
      in the molecular background of infertility.

PMID- 28432984
TI  - Cigarette smoke extract counteracts atheroprotective effects of high laminar flow
      on endothelial function.
AB  - Tobacco smoking and hemodynamic forces are key stimuli in the development of
      endothelial dysfunction and atherosclerosis. High laminar flow has an
      atheroprotective effect on the endothelium and leads to a reduced response of
      endothelial cells to cardiovascular risk factors compared to regions with
      disturbed or low laminar flow. We hypothesize that the atheroprotective effect of
      high laminar flow could delay the development of endothelial dysfunction caused
      by cigarette smoking. Primary human endothelial cells were stimulated with
      increasing dosages of aqueous cigarette smoke extract (CSEaq). CSEaq reduced cell
      viability in a dose-dependent manner. The main mediator of cellular adaption to
      oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2) and its
      target genes heme oxygenase (decycling) 1 (HMOX1) or NAD(P)H quinone
      dehydrogenase 1 (NQO1) were strongly increased by CSEaq in a dose-dependent
      manner. High laminar flow induced elongation of endothelial cells in the
      direction of flow, activated the AKT/eNOS pathway, increased eNOS expression,
      phosphorylation and NO release. These increases were inhibited by CSEaq. Pro
      inflammatory adhesion molecules intercellular adhesion molecule-1 (ICAM1),
      vascular cell adhesion molecule-1 (VCAM1), selectin E (SELE) and chemokine (C-C
      motif) ligand 2 (CCL2/MCP-1) were increased by CSEaq. Low laminar flow induced
      VCAM1 and SELE compared to high laminar flow. High laminar flow improved
      endothelial wound healing. This protective effect was inhibited by CSEaq in a
      dose-dependent manner through the AKT/eNOS pathway. Low as well as high laminar
      flow decreased adhesion of monocytes to endothelial cells. Whereas, monocyte
      adhesion was increased by CSEaq under low laminar flow, this was not evident
      under high laminar flow. This study shows the activation of major atherosclerotic
      key parameters by CSEaq. Within this process, high laminar flow is likely to
      reduce the harmful effects of CSEaq to a certain degree. The identified molecular
      mechanisms might be useful for development of alternative therapy concepts.

PMID- 28432986
TI  - The effects of thymoquinone on hippocampal cytokine level, brain oxidative stress
      status and memory deficits induced by lipopolysaccharide in rats.
AB  - OBJECTIVE: The study objective was to determine the protective effects of
      thymoquinone (TQ) on brain tissues oxidative stress status, hippocampal cytokine
      level, and learning and memory deficits induced by lipopolysaccharide (LPS) in
      rats. METHODS: Animals were randomly divided into the following groups and
      treated: (1) Control (saline), (2) LPS (1mg/kg i.p.), (3-5) 2, 5 or 10mg/kg TQ
      extract 30min before LPS injection. The treatment was started since two weeks
      before the behavioral experiments and continued during the behavioral tests (LPS
      injected 2h before each behavioral experiment). Finally, the brains were removed
      for biochemical assessments. RESULTS: Morris water maze (MWM) test results showed
      that LPS increased escape latency compared to control group whereas TQ decreased
      them vs. LPS group. In passive avoidance (PA) test, LPS reduced the latency to
      enter the dark compartment vs. control group, while TQ treatment attenuated this
      effect of LPS. Additionally, LPS increased interleukin-6 (IL-6) and tumor
      necrosis alpha (TNF-alpha) in the hippocampal tissues. It also elevated
      malondialdehyde (MDA) and nitric oxide (NO) metabolites and decreased thiol
      content, superoxide dismutase (SOD) and catalase (CAT) in both hippocampus and
      cortex vs. control group, while TQ decreased IL-6, TNF-alpha, MDA and NO
      metabolites and increased thiol content, SOD and CAT compared to LPS group.
      CONCLUSION: Findings of current study indicated that TQ improved LPS-induced
      learning and memory impairments induced by LPS in rats by attenuating the
      hippocampal cytokine levels and brain tissues oxidative damage.

PMID- 28432988
TI  - Comprehension of concrete and abstract words in semantic variant primary
      progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.
AB  - The aim of this study was to investigate the comprehension of concrete, abstract
      and abstract emotional words in semantic variant primary progressive aphasia
      (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups
      of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological
      assessment, a similarity judgment task, and structural brain MRI. The three types
      of words were processed similarly in the group of AD participants. In contrast,
      patients in the svPPA group were significantly more impaired at processing
      concrete words than abstract words, while comprehension of abstract emotional
      words was in between. VBM analyses showed that comprehension of concrete words
      relative to abstract words was significantly correlated with atrophy in the left
      anterior temporal lobe. These results support the view that concrete words are
      disproportionately impaired in svPPA, and that concrete and abstract words may
      rely upon partly dissociable brain regions.

PMID- 28432987
TI  - Multimodal imaging of language reorganization in patients with left temporal lobe
      epilepsy.
AB  - This study explored the relationships among multimodal imaging, clinical
      features, and language impairment in patients with left temporal lobe epilepsy
      (LTLE). Fourteen patients with LTLE and 26 controls underwent structural MRI,
      functional MRI, diffusion tensor imaging, and neuropsychological language tasks.
      Laterality indices were calculated for each imaging modality and a principal
      component (PC) was derived from language measures. Correlations were performed
      among imaging measures, as well as to the language PC. In controls, better
      language performance was associated with stronger left-lateralized temporo
      parietal and temporo-occipital activations. In LTLE, better language performance
      was associated with stronger right-lateralized inferior frontal, temporo
      parietal, and temporo-occipital activations. These right-lateralized activations
      in LTLE were associated with right-lateralized arcuate fasciculus fractional
      anisotropy. These data suggest that interhemispheric language reorganization in
      LTLE is associated with alterations to perisylvian white matter. These concurrent
      structural and functional shifts from left to right may help to mitigate language
      impairment in LTLE.

PMID- 28432989
TI  - The effect of natural ventilation strategy on indoor air quality in schools.
AB  - In order to reduce children's exposure to pollutants in classrooms a proper
      ventilation strategy need to be adopted. Such strategy is even more important in
      naturally ventilated schools where the air exchange rate is only based on the
      manual airing of classrooms. The present work aimed to evaluate the effect of the
      manual airing strategy on indoor air quality in Italian classrooms. For this aim,
      schools located in the Central Italy were investigated. Indoor air quality was
      studied in terms of CO2, particle number and PM concentrations and compared to
      corresponding outdoor levels. In particular two experimental analyses were
      performed: i) a comparison between heating and non heating season in different
      schools; ii) an evaluation of the effect of scheduled airing periods on the
      dilution of indoor-generated pollutants and the penetration of outdoor-generated
      ones. In particular, different airing procedures, i.e. different window opening
      periods (5 to 20min per hour) were imposed and controlled through contacts
      installed on classroom windows and doors. Results revealed that the airing
      strategy differently affect the several pollutants detected in indoors depending
      on their size, origin and dynamics. Longer airing periods may result in reduced
      indoor CO2 concentrations and, similarly, other gaseous indoor-generated
      pollutants. Simultaneously, higher ultrafine particle (and other vehicular
      related pollutants) levels in indoors were measured due to infiltration from
      outdoors. Finally, a negligible effect of the manual airing on PM levels in
      classroom was detected. Therefore, a simultaneous reduction in concentration
      levels for all the pollutant metrics in classrooms cannot be obtained just
      relying upon air permeability of the building envelope and manual airing of the
      classrooms.

PMID- 28432990
TI  - Influence of red mud on soil microbial communities: Application and comprehensive
      evaluation of the Biolog EcoPlate approach as a tool in soil microbiological
      studies.
AB  - Red mud can be applied as soil ameliorant to acidic, sandy and micronutrient
      deficient soils. There are still knowledge gaps regarding the effects of red mud
      on the soil microbial community. The Biolog EcoPlate technique is a promising
      tool for community level physiological profiling. This study presents a detailed
      evaluation of Biolog EcoPlate data from two case studies. In experiment "A" red
      mud from Ajka (Hungary) was mixed into acidic sandy soil in soil microcosms at 5
      50 w/w%. In experiement "B" red mud soil mixture was mixed into low quality
      subsoil in a field experiment at 5-50 w/w%. According to average well color
      development, substrate average well color development and substrate richness 5
      20% red mud increased the microbial activity of the acidic sandy soil over the
      short term, but the effect did not last for 10months. Shannon diversity index
      showed that red mud at up to 20% did not change microbial diversity over the
      short term, but the diversity decreased by the 10th month. 30-50% red mud had
      deteriorating effect on the soil microflora. 5-20% red mud soil mixture in the
      low quality subsoil had a long lasting enhancing effect on the microbial
      community based on all Biolog EcoPlate parameters. However, 50% red mud soil
      mixture caused a decrease in diversity and substrate richness. With the Biolog
      EcoPlate we were able to monitor the changes of the microbial community in red
      mud affected soils and to assess the amount of red mud and red mud soil mixture
      applicable for soil treatment in these cases.

PMID- 28432991
TI  - Characteristics of adapted hydrogenotrophic community during biomethanation.
AB  - The results presented in this study were carried out as concomitant experiments
      during the start-up and operation of a biomethanation unit to evaluate the effect
      of process parameters on carbon conversion, product formation (methane and
      acetate) and community composition. For that, two different samples were
      withdrawn from a trickle-bed reactor with immobilized enrichment culture of
      hydrogenotrophic methanogens adapted from sewage sludge. One sample was taken
      from the recirculation liquid during start-up phase while the other was withdrawn
      directly from the carrier material in the reactor. Elevated acid levels
      especially during start-up were shown to affect the overall carbon conversion.
      This effect was also seen during the acid tolerance testing reported here. Final
      acid concentrations of 1.6+/-0.3g/L resulted in a reduced conversion ratio of
      only 46%. Without acid addition complete conversion of CO2 in the headspace was
      achieved. However, maximum methane production of 0.55+/-0.02mmol after 4days of
      incubation was monitored at moderate initial acetate concentration of 0.4g/L. In
      both analyzed inoculation materials Methanobacterium species were by far the most
      dominant Archaea with 21.8% in the recirculation liquid during start-up and 84.8%
      in the enrichment culture immobilized on the carrier material. The microbial
      composition of the two analyzed samples is in accordance with the results
      obtained for the carbon conversion and product formation. With approximately 50%
      of Bacteroidetes and Firmicutes present during reactor start-up the acetic acid
      production significantly contributed to the overall carbon conversion. In
      contrast, methane was produced almost exclusively in trials representing
      continuous operation where acetogenic bacteria accounted only up to 17.5%. In
      summary, the acid accumulation monitored during reactor start-up of a
      biomethanation unit is most likely to result from the microbial composition
      present. Nevertheless, complete adaptation to hydrogenotrophic conditions was
      proven to alter the consortium and yield methane as main product alongside high
      carbon conversion of up to 70.5+/-1.8%.

PMID- 28432992
TI  - Bioaccumulation kinetics of copper in Ruditapes philippinarum exposed to
      increasing, continuous and pulsed exposure: Implications for growth.
AB  - Metal bioaccumulation and toxicity to aquatic organisms depends on factors such
      as magnitude, duration and frequency of the exposure. The type of the exposure
      affects the toxicokinetic processes in the organisms. In this study, we carried
      out 30-day toxicity tests on juveniles of Ruditapes philippinarum exposed to
      increasing, continuous and pulsed exposure. Organisms were exposed to copper
      spiked sediments followed by a 10-day recovery period. We assessed the
      interaction between the kinetics of subcellular copper partitioning and the
      growth response. Results showed that the growth rate of the bivalve was inversely
      correlated to the bioaccumulation rate and that sublethal copper concentrations
      stimulated the detoxification mechanisms inside the organism regardless the type
      of the exposure. However, a large stimulatory effect on growth was observed
      during the recovery period, associated with significant negative accumulation
      rate values and dependent on the type of antecedent exposure. This suggested that
      on individual and short-term basis pulsed exposures have a more adverse effect
      compared to increasing or continuous exposure scenarios.

PMID- 28432993
TI  - Chemical, biological, and DNA markers for tracing slaughterhouse effluent.
AB  - Agricultural practices, if not managed correctly, can have a negative impact on
      receiving environments via waste disposal and discharge. In this study, a chicken
      slaughter facility on the rural outskirts of Sydney, Australia, has been
      identified as a possible source of persistent effluent discharge into a peri
      urban catchment. Questions surrounding the facility's environmental management
      practices go back more than four decades. Despite there having never been a
      definitive determination of the facility's impact on local stream water quality,
      the New South Wales Environment Protection Authority (NSW EPA) has implemented
      numerous pollution reduction requirements to manage noise and water pollution at
      the slaughter facility. However, assessment of compliance remains complicated by
      potential additional sources of pollution in the catchment. To unravel this long
      standing conundrum related to water pollution we apply a forensic, multiple lines
      of evidence approach to delineate the origin of the likely pollution source(s).
      Water samples collected between 2014 and 2016 from irrigation pipes and a
      watercourse exiting the slaughter facility had elevated concentrations of ammonia
      (max: 63,000ug/L), nitrogen (max: 67,000ug/L) and phosphorus (max: 39,000ug/L),
      which were significantly higher than samples from adjacent streams that did not
      receive direct runoff from the facility. Arsenic, sometimes utilised in growth
      promoting compounds, was detected in water discharging from the facility up to ~4
      times (max 3.84ug/L) local background values (<0.5ug/L), with inorganic
      As(?V+III) being the dominant species. The spatial association of elevated water
      pollution to the facility could not unequivocally distinguish a source and
      consequently DNA analysis of a suspected pollution discharge event was
      undertaken. Analysis of catchment runoff from several local streams showed that
      only water sampled at the downstream boundary of the facility tested positive for
      chicken DNA, with traces of duck DNA being absent, which was a potential
      confounder given that wild ducks are present in the area. Further, PCR analysis
      showed that only the discharge water emanating from the slaughter facility tested
      positive for a generalized marker of anthropogenic pollution, the clinical class
      1 integron-integrase gene. The environmental data collected over a three-year
      period demonstrates that the slaughter facility is indisputably the primary
      source of water-borne pollution in the catchment. Moreover, application of DNA
      and PCR for confirming pollution sources demonstrates its potential for
      application by regulators in fingerprinting pollution sources.

PMID- 28432995
TI  - Eye disorder differentiates seasonality outcomes in persons with severe visual
      impairment.
AB  - BACKGROUND: Light plays a crucial role in both the pathogenesis and treatment of
      seasonal affective disorder (SAD). Consequently decreased retinal sensitivity to
      light has been suggested to be a risk factor for SAD. In a population of persons
      with severe visual impairment we recently found a highly increased prevalence of
      SAD. We now aimed to identify eye disorders or anatomical locations with specific
      association to seasonality. METHODS: In 912 cases (33%) from our prior seasonal
      pattern assessment questionnaire (SPAQ) screening study, we retrieved eye
      diagnoses from the Danish National Patient Registry and analyzed for specific eye
      disorders or anatomical locations that significantly differentiated SPAQ outcomes
      (global seasonality score, (GSS) and SPAQ-SAD prevalence). RESULTS: Persons with
      early life eye disorders (congenital conditions or retinopathy of prematurity)
      reported less symptoms of SAD (median GSS 4.5) than persons with acquired eye
      disorders (median GSS 5.0, p=0.005). Persons with macular degenerative disorders
      (MD) had highly increased seasonality outcomes (hazard ratio 2.23, p=0.002,
      median GSS 5 vs. 8, p=0.01). LIMITATIONS: the study is a cross-sectional study
      based on a self-report questionnaire. Register data may be incomplete.
      CONCLUSIONS: MD is significantly associated to high-level seasonality and SAD
      prevalence. Early life eye disorder is associated to slightly lower seasonality
      compared to acquired eye disorder. Longitudinal studies are needed to assess
      causality.

PMID- 28432994
TI  - Assessment of temporal variation for the risk of particulate matters on asthma
      hospitalization.
AB  - Increased ambient concentration of particulate matters are considered as one of
      major causes for increased prevalence or exacerbation of asthma or asthma like
      symptoms. Recently, possible temporal variation in risks of PM on mortality has
      been suggested. We investigated short-term effect of both PM10 and PM2.5 on
      asthma hospitalization, and assessed temporal variation of PM risks in Seoul,
      Korea, 2003-2011. Generalized additive model was used to estimate PM risks on
      asthma hospitalization with consideration by long-term trend, influenza epidemic,
      day of week, meteorological factors. To assess temporal variation of PM risks,
      year-round PM risks were estimated. Stratified analysis by season and age-group
      were also conducted. Estimated RRs of PM on asthma hospitalization by an increase
      of 10?/?were 1.0084 (95% CI: 1.0041-1.0127) and 1.0156 (95% CI: 1.0055-1.0259)
      respectively with 7-days lag periods (lag06). PM2.5 had stronger effect than PM10
      for all age group. Elderly group was most affected by PM. For the analysis of
      temporal variation of PM risks, we found increasing trend in total population and
      the elderly group. In the season-specific analysis, we also found increasing
      trend in winter for PM10, and in spring for PM2.5. PM10 and PM2.5 has adverse
      effect on asthma hospitalization with evidence suggesting temporal variation in
      PM risks. Further research will be needed to confirm the temporal variation of PM
      risk on asthma hospitalization, and to identify casual factors affecting this
      temporal variation. This study results could be evidentiary materials for
      establishing valid public health policies to reduce health burden or economic
      burden of asthma.

PMID- 28432996
TI  - Toxicological effects of phenol on four marine microalgae.
AB  - The toxic effects of phenol on four marine microalgae (Dunaliella salina,
      Platymonas subcordiformis, Phaeodactylum tricornutum Bohlin, and Skeletonema
      costatum) were evaluated. The 96h EC50 values were 72.29, 92.97, 27.32, and
      27.32mgL-1, respectively, which were lower than those values of freshwater
      microalgae reported in the literature. During a 96-h exposure to a sub-lethal
      concentration of phenol (1/2 96h EC50) with green alga (D. salina) and diatom (S.
      costatum), reactive oxygen species (ROS) accumulation, and chlorophyll a (Chl a)
      content decrease were simultaneously observed in diatom cells after 48h
      treatment. On the contrary, other chlorophylls in both algae were unaffected.
      Under transmission electron microscopy (TEM), the phenol-induced ultrastructure
      alterations included disappearance, or shrinkage, of nucleolus and enlargement of
      vacuoles, which may result in programmed cell death (PCD). The increase in number
      of lipid droplets may be related to phenol detoxification. These results indicate
      that the sensitivity of marine microalgae to phenol was dependent on some biotic
      factors such as cell size, ROS production, and phenol degradation ability in
      algal cells.

PMID- 28432997
TI  - Serum uric acid level is linked to the disease progression rate in male patients
      with multiple system atrophy.
AB  - OBJECTIVES: Multiple system atrophy (MSA) is a progressive neurodegenerative
      disorder that may be caused in part by oxidative stress. Uric acid (UA) protects
      neurons in neurodegenerative disorders via antioxidative effects. The aim of this
      study was to investigate the relationship between the serum UA concentration and
      disease progression in MSA patients. PATIENTS AND METHODS: A total of 53 Japanese
      MSA patients were enrolled in this study. The disease progression rate was
      estimated by the rate of global disability scale change per year. The
      relationship between the serum UA concentration and disease progression was
      assessed by Spearman's correlation analysis. Disease progression depending on the
      UA concentration was also estimated by multivariate logistic regression analysis.
      RESULTS: MSA patients with the highest serum UA concentration had lower disease
      progression rates than those with the lowest concentration. Spearman's
      correlation analysis showed an inverse correlation between the serum UA
      concentration and disease progression in male patients. Multivariate logistic
      regression analysis confirmed that the UA concentration was independently related
      to disease progression only in male patients. CONCLUSION: These results suggest
      that serum UA may be associated with disease progression in male patients with
      MSA.

PMID- 28432998
TI  - Non-ideal effects in bending response of soft substrates covered with biomimetic
      scales.
AB  - Biomimetic scales are known to substantially alter the mechanics response of the
      underlying substrate engendering complex nonlinearities that can manifest even in
      small deformations due to scales interaction. This interaction is typically
      modeled using a-priori homogenization with an enforced periodicity of engagement.
      Such a framework is fairly useful especially when dealing with the structural
      length scale which is at least one order of magnitude greater than the scales
      themselves since individual tracking of a large number of scales become
      insurmountable. On the other hand, this scheme makes several assumptions whose
      validity has not yet been investigated including infinite length of the substrate
      and rigidity of the scales. The validity of these assumptions and the accuracy
      and limitations of associated analytical models are investigated. Finite element
      based numerical studies were carried out to identify the critical role of edge
      effects and other non-ideal behavior such as violation of periodicity and
      nonlinear constitutive response on scale rotation. Our investigation shows that
      several important quantities show a strong saturation characteristic which
      justify many of the simplifying assumptions whereas others need much greater
      care.

PMID- 28432999
TI  - Effect of intra-oral aging on t->m phase transformation, microstructure, and
      mechanical properties of Y-TZP dental ceramics.
AB  - The aim of the present study was to evaluate the influence of intra-oral aging on
      the tetragonal-to-monoclinic (t->m) phase transformation of two Y-TZP dental
      ceramics - Lava Frame (Frame) and Lava Plus (Plus) - and determine the impact of
      this response on their microstructures and mechanical properties: flexural
      strength, Young's modulus, microhardness and fracture toughness. Standardized
      ceramic specimens were analyzed by X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and atomic force microscopy (AFM). After the baseline analysis,
      the specimens were attached to personalized intra-oral resin appliances and
      exposed to the oral cavity of 20 subjects for 60 days and then analyzed again.
      Specimens produced for mechanical properties evaluation were also analyzed before
      and after the 60-day intra-oral aging. The data were analyzed using two-way ANOVA
      and Tukey HSD's post hoc test (alpha=0.05). Weibull analysis was used to evaluate
      the strength reliability. Both Y-TZP ceramics suffered t->m phase transformation
      after 60-day intra-oral aging (Plus=4.7%/Frame=7.7%). SEM and AFM analyses showed
      dislodgement of ZrO2 grains and a significant increase in roughness after intra
      oral aging for both ceramics. Both Y-TZP ceramics suffered a decrease on flexural
      strength, Young's modulus and fracture toughness after intra-oral aging (p<0.05).
      Only Plus presented a decrease of microhardness after intra-oral aging (p<0.05).
      Intra-oral aging for 60 days produced t->m phase transformation, changed the
      microstructure and decreased the mechanical properties of two Y-TZP dental
      ceramics.

PMID- 28433000
TI  - Elastic moduli of electrospun mats: Importance of fiber curvature and specimen
      dimensions.
AB  - Success of tissue engineering relies on the architecture and properties of porous
      scaffolds. Electrospun nonwoven scaffolds in the form of mats are unique
      materials due to large surface area to volume ratio, high porosity, versatility
      in surface functionalities and excellent mechanical properties. Maneuvering the
      mechanical behavior of the electrospun mat is a major challenge both from
      theoretical and experimental perspectives. Herein, we report a two-dimensional
      (2D) analytical model of normalized elastic moduli of electrospun mats by
      formulating a relationship with the governing fiber and structural parameters.
      The analytical model of normalized mat modulus has also accounted for fiber
      curvature in the form of sinusoidal curve along with the specimen dimensions
      considered during the uniaxial tensile test. A comparison has been made between
      the magnitudes of normalized mat modulus obtained through predictive modeling and
      the experimental results adapted from the literature. In general, a good
      agreement has been found between the theoretical and the experimental results of
      normalized moduli of electrospun mats. An interplay of some of the governing
      parameters has been analyzed through parametric analysis. Through theoretical
      modeling, the normalized amplitude of fiber crimp via fiber diameter along with
      the aspect ratio of specimen dimensions are observed to be the dominant factors
      responsible for modulating the normalized mat modulus.

PMID- 28433002
TI  - Changes in microstructure of two ammonium-based protic ionic liquids proved by in
      situ variable-temperature 1 H NMR spectroscopy: influence of anion.
AB  - In this work, changes in microstructure of two protic ionic liquids (PILs),
      namely n-butylammonium acetate (N4Ac) and n-butylammonium nitrate (N4NO3 ), are
      proved by in situ variable-temperature 1 H NMR spectroscopy at the temperature
      range from 25 to 115  degrees C, and the influence of the nature of anion is
      discussed accordingly. The results demonstrate that 1 H NMR chemical shifts of
      alkyl protons of both N4Ac and N4NO3 are almost not changed with the increasing
      of temperature, due to the absence of hydrogen bond interaction between alkyl
      protons with anions. Whereas those of + N-H of cation decrease linearly with the
      temperature increasing, indicating that the hydrogen bond interaction between + N
      H and anion weakens gradually. In addition, the strength of hydrogen bond
      interaction between + N-H and NO3- is stronger than that between + N-H and Ac- ,
      suggesting that anions have a significant influence on microstructure due to the
      acidity of a Bronsted acid. Consequently, the proton transfer from cation to
      anion is much easier in N4Ac compared to N4NO3 . Further analyses of 1 H NMR
      chemical shifts of + N-H in N4Ac at the temperature range from 100 to 115 
      degrees C suggest that the splitting of + N-H peak may be attributed to obvious
      evidence of the existence of the proton transfer from + N-H to Ac- , which leads
      to dissociate the contact ion-pair in N4Ac to form the neutral ion-pair
      'molecule'. The results will help us to extensively understand the behavior of
      proton transfer and offer us some valuable information for the design of PILs.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28433001
TI  - Principal cell types of sleep-wake regulatory circuits.
AB  - Electrophysiological recordings indicate that neurons which discharge maximally
      in association with distinct sleep-wake states are distributed through the brain,
      albeit in differing proportions. As studied using juxtacellular recording and
      labeling within the basal forebrain, four functional principal cell types are
      distinguished as: wake/paradoxical sleep (W/PS)-, slow wave sleep (SWS)-, W- and
      PS-max active. They are each comprised by both GABA and glutamate neurons, in
      addition to acetylcholine neurons belonging to the W/PS group. By their discharge
      profiles and interactions, the GABA and glutamate neurons of different groups are
      proposed to have the capacity to generate sleep-wake states with associated EEG
      and EMG activities, though to also be importantly regulated by neuromodulatory
      systems, each of which belong to one functional cell group.

PMID- 28433003
TI  - The plastid outer membrane localized LPTD1 is important for glycerolipid
      remodelling under phosphate starvation.
AB  - Glycerolipid synthesis in plants is coordinated between plastids and the
      endoplasmic reticulum (ER). A central step within the glycerolipid synthesis is
      the transport of phosphatidic acid from ER to chloroplasts. The chloroplast outer
      envelope protein TGD4 belongs to the LptD family conserved in bacteria and plants
      and selectively binds and may transport phosphatidic acid. We describe a second
      LptD-family protein in A. thaliana (atLPTD1; At2g44640) characterized by a barrel
      domain with an amino-acid signature typical for cyanobacterial LptDs. It forms a
      cation selective channel in vitro with a diameter of about 9 A. atLPTD1 levels
      are induced under phosphate starvation. Plants expressing an RNAi construct
      against atLPTD1 show a growth phenotype under normal conditions. Expressing the
      RNAi against atLPTD1 in the tgd4-1 background renders the plants more sensitive
      to light stress or phosphate limitation than the individual mutants. Moreover,
      lipid analysis revealed that digalactosyldiacylglycerol and
      sulfoquinovosyldiacylglycerol levels remain constant in the RNAi mutants under
      phosphate starvation, while these two lipids are enhanced in wild-type. Based on
      our results, we propose a function of atLPTD1 in the transport of lipids from ER
      to chloroplast under phosphate starvation, which is combinatory with the function
      of TGD4.

PMID- 28433004
TI  - Plackett-Burman Design and Response Surface Optimization of Medium Trace
      Nutrients for Glycolipopeptide Biosurfactant Production
AB  - Background: A glycolipopeptide biosurfactant produced by Pseudomonas aeruginosa
      strain IKW1 reduced the surface tension of fermentation broth from 71.31 to 24.62
      dynes/cm at a critical micelle concentration of 20.80 mg/L. The compound proved
      suitable for applications in emulsion stabilization in food, as well as in
      cosmetic and pharmaceutical formulations. Method: In the present study, Plackett
      Burman design (PBD) and response surface method (RSM) were employed to screen and
      optimize concentrations of trace nutrients in the fermentation medium, to
      increase surfactant yield. Results: The PBD selected 5 out of the 12 screened
      significant trace nutrients. The RSM, on the other hand, resulted in the
      production of 84.44 g glycolipopeptide/L in the optimized medium containing 1.25
      mg/L nickel, 0.125 mg/L zinc, 0.075 mg/L iron, 0.0104 mg/L boron, and 0.025 mg/L
      copper. Conclusion: Significant second-order quadratic models for biomass
      (P<0.05; adjusted R2=94.29%) and biosurfactant (R2=99.44%) responses suggest
      excellent goodness-of-fit of the models. However, their respective non
      significant lack-of-fit (Biomass: F=1.28; P=0.418; Biosurfactant: F=1.20;
      P=0.446) test results indicate their adequacy to explain data variations in the
      experimental region. The glycolipopeptide is recommended for the formulation of
      inexpensive pharmaceutical products that require surface-active compounds.

PMID- 28433005
TI  - Geometrical eigen-subspace framework based molecular conformation representation
      for efficient structure recognition and comparison.
AB  - We have developed an extended distance matrix approach to study the molecular
      geometric configuration through spectral decomposition. It is shown that the
      positions of all atoms in the eigen-space can be specified precisely by their
      eigen-coordinates, while the refined atomic eigen-subspace projection array
      adopted in our approach is demonstrated to be a competent invariant in structure
      comparison. Furthermore, a visual eigen-subspace projection function (EPF) is
      derived to characterize the surrounding configuration of an atom naturally. A
      complete set of atomic EPFs constitute an intrinsic representation of molecular
      conformation, based on which the interatomic EPF distance and intermolecular EPF
      distance can be reasonably defined. Exemplified with a few cases, the
      intermolecular EPF distance shows exceptional rationality and efficiency in
      structure recognition and comparison.

PMID- 28433006
TI  - Electrolyte solutions at curved electrodes. I. Mesoscopic approach.
AB  - Within the Poisson-Boltzmann approach, electrolytes in contact with planar,
      spherical, and cylindrical electrodes are analyzed systematically. The
      dependences of their capacitance C on the surface charge density sigma and the
      ionic strength I are examined as a function of the wall curvature. The surface
      charge density has a strong effect on the capacitance for small curvatures,
      whereas for large curvatures the behavior becomes independent of sigma. An
      expansion for small curvatures gives rise to capacitance coefficients which
      depend only on a single parameter, allowing for a convenient analysis. The
      universal behavior at large curvatures can be captured by an analytic expression.

PMID- 28433007
TI  - Alternative definition of excitation amplitudes in multi-reference state-specific
      coupled cluster.
AB  - A central difficulty of state-specific Multi-Reference Coupled Cluster (MR-CC) in
      the multi-exponential Jeziorski-Monkhorst formalism concerns the definition of
      the amplitudes of the single and double excitation operators appearing in the
      exponential wave operators. If the reference space is a complete active space
      (CAS), the number of these amplitudes is larger than the number of singly and
      doubly excited determinants on which one may project the eigenequation, and one
      must impose additional conditions. The present work first defines a state
      specific reference-independent operator T~^m which acting on the CAS component of
      the wave function |Psi0m? maximizes the overlap between (1+T~^m)|Psi0m? and the
      eigenvector of the CAS-SD (Singles and Doubles) Configuration Interaction (CI)
      matrix |PsiCAS-SDm?. This operator may be used to generate approximate
      coefficients of the triples and quadruples, and a dressing of the CAS-SD CI
      matrix, according to the intermediate Hamiltonian formalism. The process may be
      iterated to convergence. As a refinement towards a strict coupled cluster
      formalism, one may exploit reference-independent amplitudes provided by
      (1+T~^m)|Psi0m? to define a reference-dependent operator T^m by fitting the
      eigenvector of the (dressed) CAS-SD CI matrix. The two variants, which are
      internally uncontracted, give rather similar results. The new MR-CC version has
      been tested on the ground state potential energy curves of 6 molecules (up to
      triple-bond breaking) and two excited states. The non-parallelism error with
      respect to the full-CI curves is of the order of 1 mEh.

PMID- 28433008
TI  - Nonlinear permittivity spectra of supercooled ionic liquids: Observation of a
      "hump" in the third-order permittivity spectra and comparison to double-well
      potential models.
AB  - We have measured the third-order permittivity spectra epsilon33 of a monocationic
      and of a dicationic liquid close to the glass transition temperature by applying
      ac electric fields with large amplitudes up to 180 kV/cm. A peak ("hump") in the
      modulus of epsilon33 is observed for a mono-cationic liquid after subtraction of
      the dc contribution from the imaginary part of epsilon33. We show that the origin
      of this experimental "hump" is a peak in the imaginary part of epsilon33, with
      the peak height strongly increasing with decreasing temperature. Overall, the
      spectral shape of the third-order permittivity of both ionic liquids is similar
      to the predictions of a symmetric double well potential model, although this
      model does not predict a "hump" in the modulus. In contrast, an asymmetric double
      well potential model predicts a "hump," but the spectral shape of both the real
      and imaginary part of epsilon33 deviates significantly from the experimental
      spectra. These results show that not only the modulus of epsilon33 but also its
      phase is an important quantity when comparing experimental results with
      theoretical predictions.

PMID- 28433009
TI  - Equation-of-motion coupled-cluster methods for atoms and molecules in strong
      magnetic fields.
AB  - A program for the direct calculation of excitation energies of atoms and
      molecules in strong magnetic fields is presented. The implementation includes the
      equation-of-motion coupled-cluster singles-doubles (EOM-CCSD) method for
      electronically excited states as well as its spin-flip variant. Differences to
      regular EOM-CCSD implementations are due to the appearance of the canonical
      angular-momentum operator in the Hamiltonian causing the wave function to become
      complex. The gauge-origin problem is treated by the use of gauge-including atomic
      orbitals. Therefore, a modified Davidson method for diagonalizing complex non
      Hermitian matrices is used. Excitation energies for selected atoms and molecules
      that are of importance in the astrochemical context are presented and their
      dependence on the magnetic field is discussed.

PMID- 28433010
TI  - About the nature of halogen bond interaction under the spatial confinement.
AB  - Nowadays, much attention is put toward the description of noncovalent complexes
      exposed to the high pressure or embedded in confining environments. Such
      conditions may strongly modify the physical and chemical properties of molecular
      systems. This study focuses on the theoretical description of the confinement
      induced changes in geometry and energetic parameters of the halogen bonded
      FCl?CNF complex. A model analytical potential is applied to render the effect of
      orbital compression. In order to analyze the nature of halogen bond interaction,
      in the presence of spatial confinement, the supermolecular approach together with
      the symmetry-adapted perturbation theory is used. Furthermore, a thorough
      analysis of topological parameters, characterizing the halogen bond upon orbital
      compression, is performed within the quantum theory of atoms in molecules. The
      calculations are carried out using the omegaB97x and CCSD(T) methods in
      connection with the aug-cc-pVTZ basis set. Among others, the obtained results
      indicate that the spatial confinement not only modifies the nature of halogen
      bond interaction but also induces the appearance of a completely new form of the
      studied FCl?CNF system.

PMID- 28433012
TI  - Internal dynamics of semiflexible polymers with active noise.
AB  - The intramolecular dynamics of flexible and semiflexible polymers in response to
      active noise is studied theoretically. The active noise may either originate from
      interactions of a passive polymer with a bath of active Brownian particles or the
      polymer itself is comprised of active Brownian particles. We describe the polymer
      by the continuous Gaussian semiflexible-polymer model, taking into account the
      finite polymer extensibility. Our analytical calculations predict a strong
      dependence of the polymer dynamics on the activity. In particular, active
      semiflexible polymers exhibit a crossover from a bending elasticity-dominated
      dynamics at weak activity to that of flexible polymers at strong activity. The
      end-to-end vector correlation function decays exponentially for times longer than
      the longest polymer relaxation time. Thereby, the polymer relaxation determines
      the decay of the correlation function for long and flexible polymers. For shorter
      and stiffer polymers, the relaxation behavior of individual active Brownian
      particles dominates the decay above a certain activity. The diffusive dynamics of
      a polymer is substantially enhanced by the activity. Three regimes can be
      identified in the mean square displacement for sufficiently strong activities: an
      activity-induced ballistic regime at short times, followed by a Rouse-type
      polymer-specific regime for any polymer stiffness, and free diffusion at long
      times, again determined by the activity.

PMID- 28433013
TI  - Shape resonances, virtual state, and Ramsauer-Townsend minimum in the low-energy
      electron collisions with benzene.
AB  - In this work, we revisit the low-energy electron scattering by benzene. We
      employed the Schwinger multichannel method implemented with pseudopotentials to
      carry out systematic cross section calculations with different schemes of
      polarization for the resonant and the totally symmetric irreducible
      representations within the D2h symmetry group. We present integral and
      differential cross sections for incident electron energies up to 12 eV and
      discuss the shape resonances and the presence of a Ramsauer-Townsend minimum and
      a virtual state in the former. We also discuss the relation of these physical
      phenomena with the different schemes of the polarization effects employed in our
      calculations. Finally, the comparison of our calculated integral and differential
      cross sections with the available data from the literature suggests improvement
      in the agreement between theory and experiment.

PMID- 28433011
TI  - Ramped-amplitude NOVEL.
AB  - We present a pulsed dynamic nuclear polarization (DNP) study using a ramped
      amplitude nuclear orientation via electron spin locking (RA-NOVEL) sequence that
      utilizes a fast arbitrary waveform generator (AWG) to modulate the microwave
      pulses together with samples doped with narrow-line radicals such as 1,3
      bisdiphenylene-2-phenylallyl (BDPA), sulfonated-BDPA (SA-BDPA), and trityl-OX063.
      Similar to ramped-amplitude cross polarization in solid-state nuclear magnetic
      resonance, RA-NOVEL improves the DNP efficiency by a factor of up to 1.6 compared
      to constant-amplitude NOVEL (CA-NOVEL) but requires a longer mixing time. For
      example, at taumix = 8 MUs, the DNP efficiency reaches a plateau at a ramp
      amplitude of ~20 MHz for both SA-BDPA and trityl-OX063, regardless of the ramp
      profile (linear vs. tangent). At shorter mixing times (taumix = 0.8 MUs), we
      found that the tangent ramp is superior to its linear counterpart and in both
      cases there exists an optimum ramp size and therefore ramp rate. Our results
      suggest that RA-NOVEL should be used instead of CA-NOVEL as long as the
      electronic spin lattice relaxation T1e is sufficiently long and/or the duty cycle
      of the microwave amplifier is not exceeded. To the best of our knowledge, this is
      the first example of a time domain DNP experiment that utilizes modulated
      microwave pulses. Our results also suggest that a precise modulation of the
      microwave pulses can play an important role in optimizing the efficiency of
      pulsed DNP experiments and an AWG is an elegant instrumental solution for this
      purpose.

PMID- 28433015
TI  - Probing the effects of surface hydrophobicity and tether orientation on antibody
      antigen binding.
AB  - Antibody microarrays have the potential to revolutionize molecular detection for
      many applications, but their current use is limited by poor reliability, and
      efforts to change this have not yielded fruitful results. One difficulty which
      limits the rational engineering of next-generation devices is that little is
      known, at the molecular level, about the antibody-antigen binding process near
      solid surfaces. Atomic-level structural information is scant because typical
      experimental techniques (X-ray crystallography and NMR) cannot be used to image
      proteins bound to surfaces. To overcome this limitation, this study uses
      molecular simulation and an advanced, experimentally validated, coarse-grain,
      protein-surface model to compare fab-lysozyme binding in bulk solution and when
      the fab is tethered to hydrophobic and hydrophilic surfaces. The results show
      that the tether site in the fab, as well as the surface hydrophobicity,
      significantly impacts the binding process and suggests that the optimal design
      involves tethering fabs upright on a hydrophilic surface. The results offer an
      unprecedented, molecular-level picture of the binding process and give hope that
      the rational design of protein-microarrays is possible.

PMID- 28433016
TI  - First-principles C band absorption spectra of SO2 and its isotopologues.
AB  - The low-energy wing of the C~B21<-X~1A1 absorption spectra for SO2 in the
      ultraviolet region is computed for the 32S,33S,34S and 36S isotopes, using the
      recently developed ab initio potential energy surfaces (PESs) of the two
      electronic states and the corresponding transition dipole surface. The state
      resolved absorption spectra from various ro-vibrational states of SO2(X~1A1) are
      computed. When contributions of these excited ro-vibrational states are included,
      the thermally averaged spectra are broadened but maintain their key characters.
      Excellent agreement with experimental absorption spectra is found, validating the
      accuracy of the PESs. The isotope shifts of the absorption peaks are found to
      increase linearly with energy, in good agreement with experiment.

PMID- 28433014
TI  - Phase behavior of supported lipid bilayers: A systematic study by coarse-grained
      molecular dynamics simulations.
AB  - Solid-supported lipid bilayers are utilized by experimental scientists as models
      for biological membranes because of their stability. However, compared to free
      standing bilayers, their close proximity to the substrate may affect their phase
      behavior. As this is still poorly understood, and few computational studies have
      been performed on such systems thus far, here we present the results from a
      systematic study based on molecular dynamics simulations of an implicit-solvent
      model for solid-supported lipid bilayers with varying lipid-substrate
      interactions. The attractive interaction between the substrate and the lipid head
      groups that are closest to the substrate leads to an increased translocation of
      the lipids from the distal to the proximal bilayer-leaflet. This thereby leads to
      a transbilayer imbalance of the lipid density, with the lipid density of the
      proximal leaflet higher than that of the distal leaflet. Consequently, the order
      parameter of the proximal leaflet is found to be higher than that of the distal
      leaflet, the higher the strength of lipid interaction is, the stronger the
      effect. The proximal leaflet exhibits gel and fluid phases with an abrupt melting
      transition between the two phases. In contrast, below the melting temperature of
      the proximal leaflet, the distal leaflet is inhomogeneous with coexisting gel and
      fluid domains. The size of the fluid domains increases with increasing the
      strength of the lipid interaction. At low temperatures, the inhomogeneity of the
      distal leaflet is due to its reduced lipid density.

PMID- 28433017
TI  - Correlation of the fragility of metallic liquids with the high temperature
      structure, volume, and cohesive energy.
AB  - The thermal expansion coefficients, structure factors, and viscosities of twenty
      five equilibrium and supercooled metallic liquids have been measured using an
      electrostatic levitation (ESL) facility. The structure factor was measured at the
      Advanced Photon Source, Argonne, using the ESL. A clear connection between liquid
      fragility and structural and volumetric changes at high temperatures is
      established; the observed changes are larger for the more fragile liquids. It is
      also demonstrated that the fragility of metallic liquids is determined to a large
      extent by the cohesive energy and is, therefore, predictable. These results are
      expected to provide useful guidance in the future design of metallic glasses.

PMID- 28433018
TI  - Atomistic insight into the non-classical nucleation mechanism during
      solidification in Ni.
AB  - Nucleation is a key step during crystallization, but a complete understanding of
      the fundamental atomistic processes remains elusive. We investigate the mechanism
      of nucleation during solidification in nickel for various undercoolings using
      transition path sampling simulations. The temperature dependence of the free
      energy barriers and rate constants that we obtain is consistent with the
      predictions of classical nucleation theory and experiments. However, our analysis
      of the transition path ensemble reveals a mechanism that deviates from the
      classical picture of nucleation: the growing solid clusters have predominantly
      non-spherical shapes and consist of face-centered-cubic and random hexagonal
      close-packed coordinated atoms surrounded by a cloud of prestructured liquid. The
      nucleation initiates in regions of supercooled liquid that are characterized by a
      high orientational order with structural features that predetermine the polymorph
      selection. These results provide atomistic insight not only into the nucleation
      mechanism of nickel but also into the role of the preordered liquid regions as
      precursors for crystallization.

PMID- 28433019
TI  - Tests for, origins of, and corrections to non-Gaussian statistics. The dipole
      flip model.
AB  - Linear response approximations are central to our understanding and simulations
      of nonequilibrium statistical mechanics. Despite the success of these approaches
      in predicting nonequilibrium dynamics, open questions remain. Laird and Thompson
      [J. Chem. Phys. 126, 211104 (2007)] previously formalized, in the context of
      solvation dynamics, the connection between the static linear-response
      approximation and the assumption of Gaussian statistics. The Gaussian statistics
      perspective is useful in understanding why linear response approximations are
      still accurate for perturbations much larger than thermal energies. In this
      paper, we use this approach to address three outstanding issues in the context of
      the "dipole-flip" model, which is known to exhibit nonlinear response. First, we
      demonstrate how non-Gaussian statistics can be predicted from purely equilibrium
      molecular dynamics (MD) simulations (i.e., without resort to a full
      nonequilibrium MD as is the current practice). Second, we show that the Gaussian
      statistics approximation may also be used to identify the physical origins of
      nonlinear response residing in a small number of coordinates. Third, we explore
      an approach for correcting the Gaussian statistics approximation for nonlinear
      response effects using the same equilibrium simulation. The results are discussed
      in the context of several other examples of nonlinear responses throughout the
      literature.

PMID- 28433020
TI  - Introducing the mean field approximation to CDFT/MMpol method: Statistically
      converged equilibrium and nonequilibrium free energy calculation for electron
      transfer reactions in condensed phases.
AB  - A new theoretical method to study electron transfer reactions in condensed phases
      is proposed by introducing the mean-field approximation into the constrained
      density functional theory/molecular mechanical method with a polarizable force
      field (CDFT/MMpol). The method enables us to efficiently calculate the
      statistically converged equilibrium and nonequilibrium free energies for diabatic
      states in an electron transfer reaction by virtue of the mean field approximation
      that drastically reduces the number of CDFT calculations. We apply the method to
      the system of a formanilide-anthraquinone dyad in dimethylsulfoxide, in which
      charge recombination and cis-trans isomerization reactions can take place,
      previously studied by the CDFT/MMpol method. Quantitative agreement of the
      driving force and the reorganization energy between our results and those from
      the CDFT/MMpol calculation and the experimental estimates supports the utility of
      our method. The calculated nonequilibrium free energy is analyzed by its
      decomposition into several contributions such as those from the averaged solute
      solvent electrostatic interactions and the explicit solvent electronic
      polarization. The former contribution is qualitatively well described by a model
      composed of a coarse-grained dyad in a solution in the linear response regime.
      The latter contribution reduces the reorganization energy by more than 10
      kcal/mol.

PMID- 28433021
TI  - To kink or not: A search for long-chain cumulenones using microwave spectral
      taxonomy.
AB  - A systematic search for carbon-chain cumulenones beyond H2C4O has been undertaken
      using microwave spectral taxonomy in combination with a pulsed jet discharge
      source. No evidence was found for the C2upsilon isomer of H2C5O or its longer
      derivatives, but HC(O)C4H, the longer variant of propynal, HC(O)CCH, was
      identified instead. Its rotational and leading centrifugal distortion constants
      have been derived to high accuracy from detection of both a- and b-type lines;
      those below 40 GHz were measured using a Fabry-Perot cavity, while lines between
      40 and 72 GHz were recorded by double resonance techniques. Overwhelming evidence
      for the identification is provided by detection of HC(O)C4D, DC(O)C4H, and
      HC(18O)C4H at the expected frequencies using isotopically enriched samples.
      Because HC(18O)C4H is produced with comparable abundance when using either 18O2
      or C18O as the source of oxygen, and because H13C(O)C4H is not preferentially
      formed when starting from 13CO, atomic oxygen appears to be a key reactant in
      formation, plausibly via O insertion, e.g., H2CC2n+2H + O -> HC(O)C2n+2H + H.
      Under the same experimental conditions, HC(O)CCH is more than 10 times more
      abundant than H2C3O, regardless of the source of oxygen, and no evidence is found
      for cyclopropenone, c-C3H2O. Taken together, these observations indicate that
      propynal and longer chains with an odd number of carbon atoms are either
      energetically more stable than cumulenones of the same size, are kinetically
      favored products, or both. On the basis of the HC(O)C4H discovery, searches for
      the isovalent sulfur species, HC(S)C4H, and HC(O)C6H have been conducted. Guided
      by new quantum chemical calculations, the rotational spectra of both were
      observed in the centimeter-wave band with the same spectrometer.

PMID- 28433022
TI  - Electrolyte solutions at curved electrodes. II. Microscopic approach.
AB  - Density functional theory is used to describe electrolyte solutions in contact
      with electrodes of planar or spherical shape. For the electrolyte solutions, we
      consider the so-called civilized model, in which all species present are treated
      on equal footing. This allows us to discuss the features of the electric double
      layer in terms of the differential capacitance. The model provides insight into
      the microscopic structure of the electric double layer, which goes beyond the
      mesoscopic approach studied in Paper I. This enables us to judge the relevance of
      microscopic details, such as the radii of the particles forming the electrolyte
      solutions or the dipolar character of the solvent particles, and to compare the
      predictions of various models. Similar to Paper I, a general behavior is observed
      for small radii of the electrode in that in this limit the results become
      independent of the surface charge density and of the particle radii. However, for
      large electrode radii, non-trivial behaviors are observed. Especially the
      particle radii and the surface charge density strongly influence the capacitance.
      From the comparison with the Poisson-Boltzmann approach, it becomes apparent that
      the shape of the electrode determines whether the microscopic details of the full
      civilized model have to be taken into account or whether already simpler models
      yield acceptable predictions.

PMID- 28433023
TI  - Rotational resonance for a heteronuclear spin pair under magic-angle spinning in
      solid-state NMR.
AB  - Rotational resonance (R2) is one of the widely applied techniques in solid-state
      NMR for recoupling a homonuclear dipolar interaction under magic-angle spinning
      (MAS). R2 occurs as the result of interference between the difference of the
      chemical shifts and MAS. In this work, we extend R2 to a heteronuclear dipolar
      interaction in the interaction frame of RF irradiation. Based on the average
      Hamiltonian theory, we show that the recoupling of the heteronuclear dipolar (I
      S) interaction occurs at the recoupling conditions written as OmegaI'+/
      OmegaS'=komegar (k=0,+/-1,+/-2), where OmegaX' is the RF offset for spin-X (X = I
      or S) scaled by RF irradiation. The new recoupling sequence for a heteronuclear
      spin pair is referred to as offset-driven cross polarization along the z axis (OD
      CPZ). With the robustness for RF inhomogeneity and ten recoupling conditions to
      choose, OD-CPZ can be a useful frequency-selective cross polarization method.
      Experiments and numerical simulations are shown with the results of the
      theoretical analysis.

PMID- 28433024
TI  - Perspective: Dissipative particle dynamics.
AB  - Dissipative particle dynamics (DPD) belongs to a class of models and
      computational algorithms developed to address mesoscale problems in complex
      fluids and soft matter in general. It is based on the notion of particles that
      represent coarse-grained portions of the system under study and allow, therefore,
      reaching time and length scales that would be otherwise unreachable from
      microscopic simulations. The method has been conceptually refined since its
      introduction almost twenty five years ago. This perspective surveys the major
      conceptual improvements in the original DPD model, along with its microscopic
      foundation, and discusses outstanding challenges in the field. We summarize some
      recent advances and suggest avenues for future developments.

PMID- 28433025
TI  - A combined theoretical and experimental study of phenol-(acetylene)n (n <= 7)
      clusters.
AB  - Structures and vibrational spectra of phenol-(acetylene)n (Ph(Ac)n) clusters are
      studied by a combination of theoretical calculations and infrared (IR)
      spectroscopy. The molecular electrostatic potential features are utilized for
      generating trial geometries of the medium-sized Ph(Ac)n (n = 1, 2, 4, 6, and 7)
      clusters. These initial geometries are subjected to geometry optimization within
      the second-order Moller-Plesset (MP2) theory, employing correlation consistent
      aug-cc-pVDZ (aVDZ) basis set. Minimal nature of the reported structures is
      confirmed by doing vibrational frequency run at MP2/aVDZ level of theory using
      full calculations for n = 1 and 2 and employing grafting based molecular
      tailoring approach for the n = 4, 6, and 7. Several isomers for n >= 4 are found
      to lie in an energy window of 1 kcal mol-1 of each other. Considering the
      formidability of MP2 level investigation for the large number of isomers for n =
      6 and 7, B97-D level theory is used for studying their energetics and IR spectra.
      It is seen that the number of energetically close isomers increases with
      increasing n. Moderately size-selected IR spectra of Ph(Ac)n (n = 4 and 7),
      prepared by a supersonic jet expansion, are measured for the acetylenic C-H and
      phenolic O-H stretch regions by infrared-ultraviolet (IR-UV) double resonance
      spectroscopy combined with time-of-flight mass spectrometry. Asymmetric line
      shape of the C-H stretch band and remarkable line broadening and weakening of the
      O-H stretch band are noteworthy features of the observed spectra. These findings
      of the experimental spectra are explained by the theoretical studies. The
      averaging of the vibrational spectrum of low-lying isomers of the Ph(Ac)n
      clusters lying in a narrow energy range is found to be responsible for the
      broadening and weakening of the O-H band.

PMID- 28433026
TI  - Variational Koopman models: Slow collective variables and molecular kinetics from
      short off-equilibrium simulations.
AB  - Markov state models (MSMs) and master equation models are popular approaches to
      approximate molecular kinetics, equilibria, metastable states, and reaction
      coordinates in terms of a state space discretization usually obtained by
      clustering. Recently, a powerful generalization of MSMs has been introduced, the
      variational approach conformation dynamics/molecular kinetics (VAC) and its
      special case the time-lagged independent component analysis (TICA), which allow
      us to approximate slow collective variables and molecular kinetics by linear
      combinations of smooth basis functions or order parameters. While it is known how
      to estimate MSMs from trajectories whose starting points are not sampled from an
      equilibrium ensemble, this has not yet been the case for TICA and the VAC.
      Previous estimates from short trajectories have been strongly biased and thus not
      variationally optimal. Here, we employ the Koopman operator theory and the ideas
      from dynamic mode decomposition to extend the VAC and TICA to non-equilibrium
      data. The main insight is that the VAC and TICA provide a coefficient matrix that
      we call Koopman model, as it approximates the underlying dynamical (Koopman)
      operator in conjunction with the basis set used. This Koopman model can be used
      to compute a stationary vector to reweight the data to equilibrium. From such a
      Koopman-reweighted sample, equilibrium expectation values and variationally
      optimal reversible Koopman models can be constructed even with short simulations.
      The Koopman model can be used to propagate densities, and its eigenvalue
      decomposition provides estimates of relaxation time scales and slow collective
      variables for dimension reduction. Koopman models are generalizations of Markov
      state models, TICA, and the linear VAC and allow molecular kinetics to be
      described without a cluster discretization.

PMID- 28433027
TI  - Potential of mean force for insertion of antimicrobial peptide melittin into a
      pore in mixed DOPC/DOPG lipid bilayer by molecular dynamics simulation.
AB  - Antimicrobial peptides (AMPs) inactivate microorganisms by forming transmembrane
      pores in a cell membrane through adsorption and aggregation. Energetics of
      addition of an AMP to a transmembrane pore is important for evaluation of its
      formation and growth. Such information is essential for the characterization of
      pore forming ability of peptides in cell membranes. This study quantifies the
      potential of mean force through molecular dynamics (MD) simulation for the
      addition of melittin, a naturally occurring AMP, into a DOPC/DOPG mixed bilayer,
      a mimic of bacterial membrane, for different extents of insertion into either a
      bilayer or a pore consisting of three to six transmembrane peptides. The energy
      barrier for insertion of a melittin molecule into the bilayer was highest in the
      absence of transmembrane peptides and decreased for the number of transmembrane
      peptides from three to six, eventually approaching zero. The decrease in free
      energy for complete insertion of peptide was found to be higher for larger pore
      size. Water channel formation occurred only for insertion into pores consisting
      of three or more transmembrane peptides with the radius of water channel being
      larger for a larger number of transmembrane peptides. The structure of the pore
      was found to be paraboloid. The estimated free energy barrier for insertion of
      melittin into an ideal paraboloid pore accounting for different intermolecular
      interactions was consistent with MD simulation results. The results reported in
      this manuscript will be useful for the development of a model for nucleation of
      pores and a rational methodology for selection of synthetic antimicrobial
      peptides.

PMID- 28433028
TI  - Incorporating nuclear vibrational energies into the "atom in molecules" analysis:
      An analytical study.
AB  - The quantum theory of atoms in molecules (QTAIM) is based on the clamped nucleus
      paradigm and solely working with the electronic wavefunctions, so does not
      include nuclear vibrations in the AIM analysis. On the other hand, the recently
      extended version of the QTAIM, called the multi-component QTAIM (MC-QTAIM),
      incorporates both electrons and quantum nuclei, i.e., those nuclei treated as
      quantum waves instead of clamped point charges, into the AIM analysis using non
      adiabatic wavefunctions. Thus, the MC-QTAIM is the natural framework to
      incorporate the role of nuclear vibrations into the AIM analysis. In this study,
      within the context of the MC-QTAIM, the formalism of including nuclear
      vibrational energy in the atomic basin energy is developed in detail and its
      contribution is derived analytically using the recently proposed non-adiabatic
      Hartree product nuclear wavefunction. It is demonstrated that within the context
      of this wavefunction, the quantum nuclei may be conceived pseudo-adiabatically as
      quantum oscillators and both isotropic harmonic and anisotropic anharmonic
      oscillator models are used to compute the zero-point nuclear vibrational energy
      contribution to the basin energies explicitly. Inspired by the results gained
      within the context of the MC-QTAIM analysis, a heuristic approach is proposed
      within the context of the QTAIM to include nuclear vibrational energy in the
      basin energy from the vibrational wavefunction derived adiabatically. The
      explicit calculation of the basin contribution of the zero-point vibrational
      energy using the uncoupled harmonic oscillator model leads to results consistent
      with those derived from the MC-QTAIM.

PMID- 28433029
TI  - Early stages of clathrin aggregation at a membrane in coarse-grained simulations.
AB  - The self-assembly process of clathrin coated pits during endocytosis has been
      simulated by combining and extending coarse grained models of the clathrin
      triskelion, the adaptor protein AP2, and a flexible network membrane. The AP2's
      core, upon binding to membrane and cargo, releases a motif that can bind
      clathrin. In conditions where the core-membrane-cargo binding is weak, the
      binding of this motif to clathrin can result in a stable complex. We characterize
      the conditions and mechanisms resulting in the formation of clathrin lattices
      that curve the membrane, i.e., clathrin coated pits. The mechanical properties of
      the AP2 beta linker appear crucial to the orientation of the curved clathrin
      lattice relative to the membrane, with wild-type short linkers giving rise to the
      inward curving buds enabling endocytosis while long linkers produce upside-down
      cages and outward curving bulges.

PMID- 28433030
TI  - Spontaneous beating and synchronization of extensile active filament.
AB  - We simulate a semi-flexible active filament that exhibits spontaneous
      oscillations on clamping and show self-propulsion when left free. The activity on
      the filament relies on the nano-dimers distributed at regular intervals along the
      chain. With an emphasis on the spontaneous beating of a clamped filament, we
      demonstrate that the two competing forces necessary for oscillation are the
      elastic forces due to polymer rigidity and the active forces due to chemical
      activity. In addition, we also study the synchronization of two extensile
      filaments and the role played by non-local hydrodynamic interactions. We observe
      a phase lock scenario between the filaments during their synchronous motion.

PMID- 28433031
TI  - Crystal structures of model lithium halides in bulk phase and in clusters.
AB  - We employ lattice energy calculations and molecular dynamics simulations to
      compare the stability of wurtzite and rock salt crystal structures of four
      lithium halides (LiF, LiCl, LiBr, and LiI) modeled using the Tosi-Fumi and Joung
      Cheatham potentials, which are models frequently used in simulation studies. Both
      infinite crystals and finite clusters are considered. For the Tosi-Fumi model, we
      find that all four salts prefer the wurtzite structure both at 0 K and at finite
      temperatures, in disagreement with experiments, where rock salt is the stable
      structure and wurtzite exists as a metastable state. For Joung-Cheatham
      potentials, rock salt is more stable for LiF and LiCl, but the wurtzite structure
      is preferred by LiBr and LiI. It is clear that the available lithium halide force
      fields need improvement to bring them into better accord with the experiment.
      Finite-size clusters that are more stable as rock salt in the bulk phase tend to
      solidify as small rock salt crystals. However, small clusters of salts that
      prefer the wurtzite structure as bulk crystals tend to form structures that have
      hexagonal motifs, but are not finite-size wurtzite crystals. We show that small
      wurtzite structures are unstable due to the presence of a dipole and rearrange
      into more stable, size-dependent structures. We also show that entropic
      contributions can act in favor of the wurtzite structure at higher temperatures.
      The possible relevance of our results for simulation studies of crystal
      nucleation from melts and/or aqueous solutions is discussed.

PMID- 28433032
TI  - IR spectral assignments for the hydrated excess proton in liquid water.
AB  - The local environmental sensitivity of infrared (IR) spectroscopy to a hydrogen
      bonding structure makes it a powerful tool for investigating the structure and
      dynamics of excess protons in water. Although of significant interest, the line
      broadening that results from the ultrafast evolution of different solvated proton
      water structures makes the assignment of liquid-phase IR spectra a challenging
      task. In this work, we apply a normal mode analysis using density functional
      theory of thousands of proton-water clusters taken from reactive molecular
      dynamics trajectories of the latest generation multistate empirical valence bond
      proton model (MS-EVB 3.2). These calculations are used to obtain a vibrational
      density of states and IR spectral density, which are decomposed on the basis of
      solvated proton structure and the frequency dependent mode character.
      Decompositions are presented on the basis of the proton sharing parameter delta,
      often used to distinguish Eigen and Zundel species, the stretch and bend
      character of the modes, the mode delocalization, and the vibrational mode
      symmetry. We find there is a wide distribution of vibrational frequencies
      spanning 1200-3000 cm-1 for every local proton configuration, with the region
      2000-2600 cm-1 being mostly governed by the distorted Eigen-like configuration.
      We find a continuous red shift of the special-pair O?H+?O stretching frequency,
      and an increase in the flanking water bending intensity with decreasing delta.
      Also, we find that the flanking water stretch mode of the Zundel-like species is
      strongly mixed with the flanking water bend, and the special pair proton
      oscillation band is strongly coupled with the bend modes of the central
      H5O2+moiety.

PMID- 28433033
TI  - Model for the alpha and beta shear-mechanical properties of supercooled liquids
      and its comparison to squalane data.
AB  - This paper presents data for supercooled squalane's frequency-dependent shear
      modulus covering frequencies from 10 mHz to 30 kHz and temperatures from 168 K to
      190 K; measurements are also reported for the glass phase down to 146 K. The data
      reveal a strong mechanical beta process. A model is proposed for the shear
      response of the metastable equilibrium liquid phase of supercooled liquids. The
      model is an electrical equivalent-circuit characterized by additivity of the
      dynamic shear compliances of the alpha and beta processes. The nontrivial parts
      of the alpha and beta processes are each represented by a "Cole-Cole retardation
      element" defined as a series connection of a capacitor and a constant-phase
      element, resulting in the Cole-Cole compliance function well-known from
      dielectrics. The model, which assumes that the high-frequency decay of the alpha
      shear compliance loss varies with the angular frequency as omega-1/2, has seven
      parameters. Assuming time-temperature superposition for the alpha and beta
      processes separately, the number of parameters varying with temperature is
      reduced to four. The model provides a better fit to the data than an equally
      parametrized Havriliak-Negami type model. From the temperature dependence of the
      best-fit model parameters, the following conclusions are drawn: (1) the alpha
      relaxation time conforms to the shoving model; (2) the beta relaxation loss-peak
      frequency is almost temperature independent; (3) the alpha compliance magnitude,
      which in the model equals the inverse of the instantaneous shear modulus, is only
      weakly temperature dependent; (4) the beta compliance magnitude decreases by a
      factor of three upon cooling in the temperature range studied. The final part of
      the paper briefly presents measurements of the dynamic adiabatic bulk modulus
      covering frequencies from 10 mHz to 10 kHz in the temperature range from 172 K to
      200 K. The data are qualitatively similar to the shear modulus data by having a
      significant beta process. A single-order-parameter framework is suggested to
      rationalize these similarities.

PMID- 28433034
TI  - Direct 1H NMR evidence of spin-rotation coupling as a source of para -> ortho-H2
      conversion in diamagnetic solvents.
AB  - At ambient temperature, conversion from 100% enriched para-hydrogen (p-H2;
      singlet state) to ortho-hydrogen (o-H2; triplet state) leads necessarily to the
      thermodynamic equilibrium proportions: 75% of o-H2 and 25% of p-H2. When p-H2 is
      dissolved in a diamagnetic organic solvent, conversion is very slow and can be
      considered as arising from nuclear spin relaxation phenomena. A first relaxation
      mechanism, specific to the singlet state and involving a combination of auto
      correlation and cross correlation spectral densities, can be retained: randomly
      fluctuating magnetic fields due to inter-molecular dipolar interactions. We
      demonstrate here that (i) this dipolar mechanism is not sufficient for accounting
      for the para->ortho conversion rate, (ii) spin-rotation interaction, an intra
      molecular mechanism, behaves similarly to random-field interaction and, thus, may
      be involved in the singlet relaxation rate. Also, as the para->ortho conversion
      is monitored by proton nuclear magnetic resonance (NMR) of dissolved o-H2 (p-H2
      is NMR-silent), one has to account for H2 exchange between the liquid phase and
      the gas phase within the NMR tube, as well as for dissolution effects.
      Experimental evidence of the above statements is brought here in the case of two
      organic solvents: acetone-d6 and carbon disulfide. The observed temperature
      dependence of the para->ortho conversion rate shows that spin-rotation can be the
      dominant contribution to the p-H2 relaxation rate in the absence of tangible
      dipolar interactions. Our findings shed new light on the "mysterious" mechanism
      of the para->ortho conversion which has been searched for several decades.

PMID- 28433035
TI  - Effects of Cr-doping on the adsorption and dissociation of S, SO, and SO2 on
      Ni(111) surfaces.
AB  - Nickel-based alloys are widely applied materials in high-temperature applications
      because they exhibit superior corrosion resistance and mechanical properties. The
      effects of sulfur, which is invariably present in industrial atmospheres, on the
      early stages of oxidation of Ni-based surfaces are not well understood. Here we
      use density functional theory to investigate the interactions of sulfur, SO, and
      SO2 with the Ni(111) and Cr-doped Ni(111) surface and elucidate their electronic
      interactions and potential energy surfaces. The results show that Cr doping of
      the Ni(111) surface increases the adsorption energies of sulfur, oxygen on the
      sulfur pre-adsorbed condition, SO and SO2. Further, this increase positively
      correlates with Cr concentration on top of the Ni(111) surface, although sulfur
      does not have any preferential interaction with Cr. This explains why Cr doping
      has little effect on the activation energy of sulfur for the most preferable
      diffusion path. Nevertheless, the increase in adsorption energies indicates a
      strong interaction with Cr-doped surfaces, which is due to the Cr-enhanced charge
      transfer to sulfur adsorbates. The existence of pre-adsorbed sulfur is shown to
      have a destabilizing effect on the oxygen interactions with the surfaces. Our
      results show that Cr doping helps to stabilize the protective oxide scale on
      Ni(111) surfaces and enhances its corrosion resistance.

PMID- 28433036
TI  - An EQT-based cDFT approach for thermodynamic properties of confined fluid
      mixtures.
AB  - We present an empirical potential-based quasi-continuum theory (EQT) to predict
      the structure and thermodynamic properties of confined fluid mixtures. The
      central idea in the EQT is to construct potential energies that integrate
      important atomistic details into a continuum-based model such as the Nernst
      Planck equation. The EQT potentials can be also used to construct the excess free
      energy functional, which is required for the grand potential in the classical
      density functional theory (cDFT). In this work, we use the EQT-based grand
      potential to predict various thermodynamic properties of a confined binary
      mixture of hydrogen and methane molecules inside graphene slit channels of
      different widths. We show that the EQT-cDFT predictions for the structure,
      surface tension, solvation force, and local pressure tensor profiles are in good
      agreement with the molecular dynamics simulations. Moreover, we study the effect
      of different bulk compositions and channel widths on the thermodynamic
      properties. Our results reveal that the composition of methane in the mixture can
      significantly affect the ordering of molecules and thermodynamic properties under
      confinement. In addition, we find that graphene is selective to methane
      molecules.

PMID- 28433037
TI  - Directed motion from particle size oscillations inside an asymmetric channel.
AB  - The motion of a spherical Brownian particle in an asymmetric periodic channel is
      considered. Under an external periodic stimulus, the particle switches between
      two states with different particle radius, every half-period. Using Brownian
      dynamics simulations, we show that the particle size oscillation, combined with
      the asymmetry of the channel, induces a drift along the channel axis, directed
      towards the steeper wall of the channel. The oscillation of the particle size is
      accompanied by a time variation of the space accessible to the particle and by an
      oscillation of its diffusion coefficient. The former underlies the drift inducing
      mechanism of purely entropic nature. The latter, combined with the former, leads
      to a significant amplification of the effect. The drift velocity vanishes when
      interconversion between the states occurs either very slow or very fast, having a
      maximum in between. The position and magnitude of the maximum are discussed by
      providing an analytical approach based on intuitively appealing assumptions.

PMID- 28433038
TI  - Four-dimensional coherent electronic Raman spectroscopy.
AB  - The correlations between different quantum-mechanical degrees of freedom of
      molecular species dictate their chemical and physical properties. Generally,
      these correlations are reflected in the optical response of the system but in low
      order or low-dimensionality measurement the signals are highly averaged. Here, we
      describe a novel four-dimensional coherent spectroscopic method that directly
      correlates within and between the manifold of electronic and vibrational states.
      The optical response theory is developed in terms of both resonant and non
      resonant field-matter interactions. Using resonance to select coherences on
      specific electronic states creates opportunities to directly distinguish coherent
      dynamics on the ground and electronically excited potentials. Critically, this
      method is free from lower-order signals that have plagued other electronically
      non-resonant vibrational spectroscopies. The theory presented here compliments
      recent work on the experimental demonstration of the 4D spectroscopic method
      described. We highlight specific means by which non-trivial effects such as
      anharmonicity (diagonal and off-diagonal), mode-specific vibronic coupling, and
      curvature of the excited states manifest in different projections of the 4D
      spectrum.

PMID- 28433039
TI  - Diffusion in quasi-one-dimensional channels: A small system n, p, T, transition
      state theory for hopping times.
AB  - Particles confined to a single file, in a narrow quasi-one-dimensional channel,
      exhibit a dynamic crossover from single file diffusion to Fickian diffusion as
      the channel radius increases and the particles begin to pass each other. The long
      time diffusion coefficient for a system in the crossover regime can be described
      in terms of a hopping time, which measures the time it takes for a particle to
      escape the cage formed by its neighbours. In this paper, we develop a transition
      state theory approach to the calculation of the hopping time, using the small
      system isobaric-isothermal ensemble to rigorously account for the volume
      fluctuations associated with the size of the cage. We also describe a Monte Carlo
      simulation scheme that can be used to calculate the free energy barrier for
      particle hopping. The theory and simulation method correctly predict the hopping
      times for a two-dimensional confined ideal gas system and a system of confined
      hard discs over a range of channel radii, but the method breaks down for wide
      channels in the hard discs' case, underestimating the height of the hopping
      barrier due to the neglect of interactions between the small system and its
      surroundings.

PMID- 28433040
TI  - Predicting miscibility of binary liquids from small cluster QCE calculations.
AB  - The quantum cluster equilibrium method is applied to model binary systems of
      molecular solvents. We minimize the computational effort as well as the
      experimental input and present the results obtained for the completely miscible
      acetonitrile/acetone, benzene/acetone, and water/acetone systems, as well as for
      the hardly miscible water/benzene system. Only clusters of sizes up to n = 3 are
      applied and these are optimized employing the low-cost functional PBEh-3c. The
      thermodynamic functions of the pure liquids are in reasonable agreement with
      experiments. For both non-water containing binary systems, the Gibbs energy of
      mixing can be reproduced with an accuracy of ~0.25 kJ/mol. Water containing
      systems are not sufficiently described by small clusters. The empirical mean
      field parameter amf and exclusion volume scaling parameter bxv which depend on
      the experimental input are approximated by linear interpolation between their
      neat liquids' reference values. This makes the approach independent from the
      experimental data of the binary system. Despite the roughness of the
      approximation as well as the small size of the cluster sets, the approach is able
      to correctly predict the mixing behavior of all acetone systems. The
      benzene/water system is correctly predicted to be non-miscible at most mole
      fractions. A small range at high benzene concentrations (x> 0.8) is falsely
      predicted to be miscible.

PMID- 28433041
TI  - Path integral molecular dynamics with surface hopping for thermal equilibrium
      sampling of nonadiabatic systems.
AB  - In this work, a novel ring polymer representation for a multi-level quantum
      system is proposed for thermal average calculations. The proposed representation
      keeps the discreteness of the electronic states: besides position and momentum,
      each bead in the ring polymer is also characterized by a surface index indicating
      the electronic energy surface. A path integral molecular dynamics with surface
      hopping (PIMD-SH) dynamics is also developed to sample the equilibrium
      distribution of the ring polymer configurational space. The PIMD-SH sampling
      method is validated theoretically and by numerical examples.

PMID- 28433042
TI  - [Alarmins and surgical injury].
AB  - Surgical intervention is an inseparable part of the management of serious
      surgical disease. However, surgery also presents a potential risk related to the
      so-called surgical injury causing immune response. When dysregulated the immune
      activation is able to cause local complications (i.e. wound dehiscence, impaired
      healing). Systemic decompartmentization of the immunologic disturbance can
      negatively influence long-term outcomes (i.e. hospital length of stay,
      mortality). Due to aseptic conditions in the operating room, such an immune
      activation is almost always of sterile nature. This involves the release of
      alarmins, protein-based molecules of the damage-associated molecular patterns
      family. The group includes e.g. high-mobility group box 1, heat-shock proteins,
      proteins S100A, and more. Under normal conditions, alarmins fulfil their
      physiologic intracellular functions. When the cell is stressed and/or damaged,
      alarmins are released into the extracellular space where they probably play their
      cytokine-like roles activating preferably the innate immune system. A number of
      experimental and clinical publications have been published concerning the role of
      alarmins in various acute and chronic diseases. However, to date a potential
      relationship between alarmins and surgical injury has not been extensively
      studied. Identification of alarmins that influence the pathological physiology of
      surgical trauma might play a role in the improvement of monitoring and predicting
      outcomes after major surgery.Key words: alarmins immune response major surgery
      sterile injury.

PMID- 28433043
TI  - [Complete minimally invasive Ivor-Lewis esophageal resection].
AB  - INTRODUCTION: Minimally invasive esophagectomy is becoming a standard procedure
      in the treatment of esophageal cancer. We would like to present our experience
      with Ivor Lewis esophagectomy completed by minimally invasive technique. METHODS:
      The primary aim of the study was to analyse potential technical difficulties and
      intraoperative complications of thoracolaparoscopic Ivor Lewis esophagectomy with
      intrathoracic anastomosis. A secondary aim of the study was to evaluate
      postoperative complications according to the Clavien-Dindo classification. The
      inclusion criterion for the study was a history of thoracolaparoscopic
      esophagectomy. Multidisciplinary approach was employed in the diagnosis, surgery
      indications and perioperative care of all patients. RESULTS: Between January 2011
      and January 2016, 19 patients underwent completely minimally invasive
      esophagectomy with intrathoracic anastomosis. There were 13 men and 6 women.
      Adenocarcinoma was confirmed by histopathological examination in all the
      patients. The cumulative postoperative morbidity was 68.4%. According to the
      Clavien-Dindo classification, we recorded grade I complications in 10.5% of the
      patients, grade II in 15.8%, grade III in 36.8% and grade IV in 5.3% of the
      patients. Anastomotic leak was the most serious complication; it was initially
      managed by negative pressure (vacuum) therapy followed by stent implantation.
      Postoperative mortality was 0%. Mean hospital stay was 12 days and mean stay at
      intensive care unit was 3.6 days. CONCLUSIONS: The basic oncosurgical principles
      of radicality need to be respected during minimally invasive procedures. However,
      functionality, safety, and cost effectiveness have to be preserved as well. In
      this paper, we present thoracolaparoscopic Ivor Lewis esophagectomy as one of
      feasible and accessible options of intrathoracic anastomosis. It seems to be safe
      with respect to technical obstacles, short-term and long-term complications.Key
      words: esophagectomy - intrathoracic - anastomosis - laparoscopy - thoracoscopy.

PMID- 28433044
TI  - [Laparoscopic diverting ileostomy in rectal cancer surgery].
AB  - INTRODUCTION: Low anterior resection (LAR) with total mesorectal excision (TME)
      represents the gold standard for patients with low rectal carcinoma. Protective
      ileostomy (PI) is commonly performed during LAR in an effort to protect low
      rectal anastomosis. The aim of this study is to analyse outcomes in our own
      patient population, focusing on morbidity associated with PI. METHOD: A
      retrospective clinical study of patients operated on between 2013 and 2015 was
      conducted in University Hospital Ostrava. All patients after LAR with PI due to
      low rectal cancer were included. The study design did not require randomisation.
      RESULTS: A total of 52 patients who underwent LAR with PI were included. Mean
      tumour height was 9.1+/-2.3 cm. 15.4% of the patients were classified as ASA I,
      53.8% were classified as ASA II and 32.7% of the patients as ASA III. 30-day
      postoperative morbidity was 38.5%, and complications associated with PI (within
      30 days after LAR) occurred in 7 (13.5%) patients. Three of these patients
      underwent urgent surgical revision due to small bowel obstruction (PI
      semirotation around its longitudinal axis in two patients and volvulus of the
      small bowel around PI in one patient). Mean time interval between PI creation and
      reversal was 252 days. During this period, complications associated with PI were
      detected in 25 (48.1%) patients; seven patients had more than one complication.
      Minor complications (such as peristomal dermatitis, stoma herniation or bleeding,
      wound infection after stoma reversal) were observed in 17 (32.7%) patients. Major
      complications (small bowel obstruction at the site of PI, dehydration due to high
      stoma output, intraabdominal abscess after stoma reversal) occurred in 8 (15.4%)
      patients. CONCLUSIONS: PI offers protection to low colorectal or coloanal
      anastomosis in rectal cancer surgery. However, this benefit is counterbalanced by
      a high risk of various complications which may occur during the whole period when
      PI is present. The decision for diversion should therefore be made only after
      careful consideration.Key words: rectal cancer - low anterior resection -
      laparoscopy - protective ileostomy - stoma complications.

PMID- 28433045
TI  - [Adherence to reporting guidelines in Perspectives in Surgery].
AB  - INTRODUCTION: Reporting guidelines were established to improve the quality of
      scientific papers. Currently, the most common are CONSORT (Consolidated Standards
      of Reporting Trials), STROBE (Strengthening the Reporting of Observational
      Studies in Epidemiology) and CARE (Clinical Consensus-based Case Reporting
      Guideline). Spin can be defined as (un)intentionally biased interpretation of
      results aimed at convincing readers of a positive benefit of any given
      intervention. The aim of the study was to evaluate the adherence of papers
      published in Perspectives in Surgery to CONSORT, STROBE or CARE and to identify
      the frequency of spin. METHODS: All articles published between 10/2014 and 9/2016
      were analysed. Editorials and letters to editor were excluded. Original papers
      and case reports were assessed using 12 parameters. Any conclusion not
      corresponding to outcomes from pre-defined measurements was identified as spin.
      Descriptive statistics were used. RESULTS: Of 210 articles, 144 (69%) were
      analysed - 67 (47%) retrospective studies, 3 (2%) prospective studies and 74
      (51%) case reports. The studies showed the highest compliance in terms of
      reporting the cohort size (89%). On the other hand, study limitations were
      presented in 22%. Performed investigations and interventions were described in
      all (100%) case reports. Conversely, limitations were not mentioned in any. None
      of the analysed papers met all of the 12 monitored parameters. Spin was
      identified in 47 (67%) original articles. CONCLUSION: None of the evaluated
      papers adhered completely to the current reporting guidelines. Spin occurred in
      more than 2/3 of the publications.Key words: reporting guidelines spin CONSORT
      STROBE CARE.

PMID- 28433046
TI  - [The risks of retroperitoneoscopic adrenalectomy].
AB  - INTRODUCTION: Minimally invasive adrenalectomy has become the gold standard for
      surgery of the suprarenal gland. Retroperitoneoscopic adrenalectomy with dorsal
      approach is preferred. The aim of our case report is to discuss potential
      complications that may arise from retroperitoneoscopic adrenalectomy,
      specifically an intra-operative injury of the inferior vena cava. CASE REPORT: A
      47-year-old male patient was admitted to undergo elective adrenalectomy on the
      right side. The reason for the surgery was a hormonally active adenoma with
      clinical signs of Conns syndrome. Biochemistry revealed the typical signs of
      hyperaldosteronism. A one-year history of unsuccessful treatment for hypertension
      was known. Ultrasound examination showed an enlarged suprarenal gland on the
      right side with the diameter of 5.2 cm. A CT scan confirmed the results of the
      ultrasound examination. Retroperitoneoscopic adrenalectomy was performed. The
      inferior vena cava was intraoperatively injured. The high pressure in the
      retroperitoneal space prevented bleeding. The injury to the vena cava was treated
      using a continuous stitch without the necessity of conversion to open surgery.
      The patient was discharged on the third postoperative day without any other
      complications. CONCLUSIONS: Retroperitoneoscopic approach is regarded by many
      authors as the new gold standard for adrenalectomy. However, very serious
      complications such as an injury of the inferior vena cava may occur. It is
      possible to treat this injury using retroperitoneoscopy. The risk of air
      embolization due to elevated pressure in the retroperitoneum (20 mm Hg) and open
      lumen of the IVC needs to be taken seriously.Key words: adrenalectomy -
      retroperitoneoscopy - complication.

PMID- 28433047
TI  - [Left hepatic vein injury during laparoscopic fundoplication for giant
      paraoesophageal hiatal hernia].
AB  - INTRODUCTION: After laparoscopic cholecystectomy, laparoscopic fundoplication has
      become another gold standard of minimal invasive surgery. The level of
      satisfaction of patients undergoing endoscopic surgery is almost 90%.
      Laparoscopic fundoplication, like other surgery methods, can also be burdened
      with grave complications, which could result in a fatal outcome even if the
      surgery is performed by a skilled surgeon. Even the authors themselves encounter
      complications despite their rich experience (more than 3,500 laparoscopic
      operations in the diaphragmatic hiatus area in more than 20 years). CASE REPORT:
      The authors report on a rare left hepatic vein injury during laparoscopic
      hiatoplasty and fundoplication according to Toupet for giant paraoesophageal
      hiatal hernia. CONCLUSION: For its low percentage of complications, laparoscopic
      fundoplication is considered as a safe operative method for gastroesophageal
      reflux disease and hiatal hernias. However, severe complications may still arise
      during the surgery and the surgeon should be familiar with them, be prepared for
      them and be able to manage such complications.Key words: gastroesophageal reflux
      disease hiatal hernia laparoscopic fundoplication left hepatic vein.

PMID- 28433048
TI  - [Wilkies syndrome - a rare cause of duodenal obstruction in an adult female
      patient].
AB  - Wilkies syndrome or superior mesenteric artery syndrome is a rare cause of
      obstruction of the upper part of the gastrointestinal tract caused by compression
      of the third part of the duodenum between the abdominal aorta and the superior
      mesenteric artery at its origin. Partial or complete compression of the duodenum
      is caused by a decreased aortomesenteric angle. In this paper, the authors
      present the case report of a patient with chronic upper abdominal ileus. The
      clinical course of the illness, symptoms and surgical treatment of the patient
      are presented. The discussion section then focuses on diagnostic methods,
      characteristic clinical course and management of Wilkies syndrome.Key words:
      duodenal obstruction duodenojejunostomy superior mesenteric artery syndrome.

PMID- 28433049
TI  - Erratum to: Partnering with patients in translational oncology research: ethical
      approach.

PMID- 28433051
TI  - Insect-Specific Viruses: A Historical Overview and Recent Developments.
AB  - Arthropod-borne viruses (arboviruses) have in recent years become a tremendous
      global health concern resulting in substantial human morbidity and mortality.
      With the widespread utilization of molecular technologies such as next-generation
      sequencing and the advancement of bioinformatics tools, a new age of viral
      discovery has commenced. Many of the novel agents being discovered in recent
      years have been isolated from mosquitoes and exhibit a highly restricted host
      range. Strikingly, these insect-specific viruses have been found to be members of
      viral families traditionally associated with human arboviral pathogens, including
      but not limited to the families Flaviviridae, Togaviridae, Reoviridae, and
      Bunyaviridae. These agents therefore present novel opportunities in the fields of
      viral evolution and viral/vector interaction and have tremendous potential as
      agents for biocontrol of vectors and or viruses of medical importance.

PMID- 28433052
TI  - Metabolomics: Strategies to Define the Role of Metabolism in Virus Infection and
      Pathogenesis.
AB  - Metabolomics is an analytical profiling technique for measuring and comparing
      large numbers of metabolites present in biological samples. Combining high
      throughput analytical chemistry and multivariate data analysis, metabolomics
      offers a window on metabolic mechanisms. Because they intimately utilize and
      often rewire host metabolism, viruses are an excellent choice to study by
      metabolomics techniques. Studies of the effects of viruses on metabolism during
      replication in vitro and infection in animal models or human subjects have
      provided novel insights into these networks and provided new targets for therapy
      and biomarker development. Identifying the common metabolic pathways utilized by
      viruses has the potential to reveal those that can be targeted by broad-spectrum
      antiviral and vaccine approaches.

PMID- 28433053
TI  - The Envelope Proteins of the Bunyavirales.
AB  - The Bunyavirales Order encompasses nine families of enveloped viruses containing
      a single-stranded negative-sense RNA genome divided into three segments. The
      small (S) and large (L) segments encode proteins participating in genome
      replication in the infected cell cytoplasm. The middle (M) segment encodes the
      viral glycoproteins Gn and Gc, which are derived from a precursor polyprotein by
      host cell proteases. Entry studies are available only for a few viruses in the
      Order, and in each case they were shown to enter cells via receptor-mediated
      endocytosis. The acidic endosomal pH triggers the fusion of the viral envelope
      with the membrane of an endosome. Structural studies on two members of this
      Order, the phleboviruses and the hantaviruses, have shown that the membrane
      fusion protein Gc displays a class II fusion protein fold and is homologous to
      its counterparts in flaviviruses and alphaviruses, which are positive-sense,
      single-stranded RNA viruses. We analyze here recent data on the structure and
      function of the structure of the phlebovirus Gc and hantavirus Gn and Gc
      glycoproteins, and extrapolate common features identified in the amino acid
      sequences to understand also the structure and function of their counterparts in
      other families of the Bunyavirales Order. Our analysis also identified clear
      structural homology between the hantavirus Gn and alphavirus E2 glycoproteins,
      which make a heterodimer with the corresponding fusion proteins Gc and E1,
      respectively, revealing that not only the fusion protein has been conserved
      across viral families.

PMID- 28433054
TI  - Technical aspects and challenges of colorimetric detection with microfluidic
      paper-based analytical devices (MUPADs) - A review.
AB  - Paper-based devices are a leading alternative among the main analytical tools for
      point-of-care testing, due to their portability, low-cost, and ease-of-use.
      Colorimetric readouts are the most common method of detection in these
      microfluidic devices, enabling qualitative, semi-quantitative and fully
      quantitative analysis of multiple analytes. There is a multitude of ways to
      obtain a colorimetric output in such devices, including nanoparticles, dyes,
      redox and pH indicators, and each has unique drawbacks and benefits. There are
      also multiple variables that impact the analysis of colorimetric reactions in
      microfluidic paper-based systems, including color homogeneity, image capture
      methods, and the data handling itself. Here, we present a critical review of
      recent developments and challenges of colorimetric detection on microfluidic
      paper-based analytical devices (MUPADs), and present thoughts and insights
      towards future perspectives in the area to improve the use of colorimetric
      readouts in conjunction with MUPADs.

PMID- 28433050
TI  - Zoonotic Potential of Emerging Paramyxoviruses: Knowns and Unknowns.
AB  - The risk of spillover of enzootic paramyxoviruses and the susceptibility of
      recipient human and domestic animal populations are defined by a broad collection
      of ecological and molecular factors that interact in ways that are not yet fully
      understood. Nipah and Hendra viruses were the first highly lethal zoonotic
      paramyxoviruses discovered in modern times, but other paramyxoviruses from
      multiple genera are present in bats and other reservoirs that have unknown
      potential to spillover into humans. We outline our current understanding of
      paramyxovirus reservoir hosts and the ecological factors that may drive
      spillover, and we explore the molecular barriers to spillover that emergent
      paramyxoviruses may encounter. By outlining what is known about enzootic
      paramyxovirus receptor usage, mechanisms of innate immune evasion, and other host
      specific interactions, we highlight the breadth of unexplored avenues that may be
      important in understanding paramyxovirus emergence.

PMID- 28433055
TI  - Pyrenyl carbon nanostructures for ultrasensitive measurements of formaldehyde in
      urine.
AB  - Measurement of ultra-low (e.g., parts-per-billion) levels of small-molecule
      markers in body fluids (e.g., serum, urine, saliva) involves a considerable
      challenge in view of designing assay strategies with sensitivity and selectivity.
      Herein we report for the first time an amperometric nano-bioelectrode design that
      uniquely combines 1-pyrenebutyric acid units pi-pi stacked with carboxylated
      multiwalled carbon nanotubes on the surface of gold screen printed electrodes for
      covalent attachment of NAD+ dependent formaldehyde dehydrogenase (FDH). The
      designed enzyme bioelectrode offered 6 ppb formaldehyde detection in 10-times
      diluted urine with a wide dynamic range of 10 ppb to 10 ppm. Fourier transform
      infrared, Raman, and electrochemical impedance spectroscopic characterizations
      confirmed the successful design of the FDH bioelectrode. Flow injection analysis
      provided lower detection limit and greater affinity for formaldehyde (apparent KM
      9.6 +/- 1.2 ppm) when compared with stirred solution method (apparent KM 19.9 +/-
      4.6 ppm). Selectivity assays revealed that the bioelectrode was selective toward
      formaldehyde with a moderate cross-reactivity for acetaldehyde (~25%) and
      negligible cross-reactivity toward propanaldehyde, acetone, methanol, and
      ethanol. Formaldehyde is an indoor pollutant, and studies have indicated
      neurotoxic characteristics and systemic toxic effects of this compound upon
      chronic and high doses of exposure. Moreover, reported chromatography and mass
      spectrometry methods identified elevated urine formaldehyde levels in patients
      with bladder cancer, dementia, and early stages of cognitive impairments compared
      to healthy people. Results demonstrate that pyrenyl carbon nanostructures-based
      FDH bioelectrode design represents novelty and simplicity for enzyme-selective
      electrochemical quantitation of small 30 Da formaldehyde. Broader applicability
      of the presented approach for other small-molecule markers is feasible that
      requires only the design of appropriate marker-specific enzyme systems or
      receptor molecules.

PMID- 28433056
TI  - Discriminative sensing of DOPA enantiomers by cyclodextrin anchored graphene
      nanohybrids.
AB  - Discriminative sensing of chiral species with a convenient and robust system is a
      challenge in chemistry, pharmaceutics and particularly in biomedical science.
      Advanced nanohybrid materials for discrimination of these biologically active
      molecules can be developed by combination of individual obvious advantages of
      different molecular scaffolds. Herein, we report on the comparison of the
      performance of cyclodextrin functionalized graphene derivatives (x-CD/rGO, x:
      alpha-, beta-, gamma-) for discrimination of DOPA enantiomers. Within this
      respect, electrochemical measurements were conducted and the experimental results
      were compared to molecular docking method. Thanks to cavity size of gamma-CD and
      the unique properties of graphene, rGO/gamma-CD nanohybrid is capable of
      selective recognition of DOPA enantiomers. Limit of detection (LOD) value and
      sensitivity were determined as 15.9 MUM and 0.2525 MUA MUM-1 for D-DOPA, and 14.9
      MUM and 0.6894 MUA MUM-1 for L-DOPA.

PMID- 28433057
TI  - Low-cost humic acid-bonded silica as an effective solid-phase extraction sorbent
      for convenient determination of aflatoxins in edible oils.
AB  - Aflatoxins (AFs) are highly toxic, mutagenic, carcinogenic, and teratogenic
      secondary metabolites produced by the toxigenic fungi Aspergillus flavus and
      Aspergillus parasiticus. AFs tend to contaminate a wide range of foods which is a
      serious and recurring food safety problem worldwide. Currently, immunoaffinity
      chromatography (IAC) has become the most conventional sample clean-up method for
      determining AFs in foodstuffs. However, IAC method is limited in the large-scale
      food analysis because it requires the use of expensive disposable cartridges and
      the IA procedure is time-consuming. Herein, to achieve the cost-effective
      determination of AFs in edible oils, we developed a promising solid-phase
      extraction (SPE) method based on commercially available humic acid-bonded silica
      (HAS) sorbent, followed by high performance liquid chromatography coupled with
      tandem mass spectrometry (HPLC-MS/MS) analysis. In HAS-SPE, AFs can be captured
      by the HAS sorbent with both hydrophobic and hydrophilic interactions, whereas
      the oil matrix was captured only with the hydrophobic interactions. The oil
      matrix can be sufficiently washed off with isopropanol, while the AFs were still
      retained on the SPE packing, thus achieving selective extraction of AFs and clean
      up of oil matrices. Under the optimal conditions of HAS-SPE, satisfactory
      recoveries ranging from 82% to 106% for four AFs (B1, B2, G1, and G2) were
      achieved in various oil matrices, containing blended oil, tea oil, rapeseed oil,
      peanut oil, sunflower seed oil, corn oil, blended olive oil, rice oil, soybean
      oil, and sesame oil. Only minor matrix effects ranging from 99% to 105% for four
      AFs were observed. Moreover, the LODs of AFs between 0.012 and 0.035 MUg/kg
      completely meet the regulatory levels fixed by the EU, China or other countries.
      The methodology was further validated for assaying the naturally contaminated
      peanut oils, and consistent results between the HAS-SPE and the referenced IAC
      were obtained. In addition, HAS-SPE can directly treat diluted oil sample without
      liquid-liquid extraction and is automatable, thus making it simple and convenient
      for the large-scale determination of AFs in edible oils. Using this method, we
      successfully detected four AFs in the naturally contaminated peanut oils, which
      is, to the best of our knowledge, the first report about the determination of AFs
      in edible oils using HA-based SPE.

PMID- 28433058
TI  - Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for
      highly specific enrichment of N-linked glycopeptides.
AB  - Protein glycosylation has been proven to participate in a variety of complex
      biological processes; however, the low abundance of glycopeptides in natural
      samples makes it essential to develop methods to isolate and enrich
      glycopeptides. In this study, a novel ultrathin Au nanowire assisted zwitterionic
      hydrophilic magnetic graphene oxide (GO-Fe3O4/SiO2/AuNWs/L-Cys) was synthesized
      with the good biocompatibility of GO, strong magnetic responses of Fe3O4, large
      surface area of ultrathin Au nanowires and excellent hydrophilicity of L-Cys via
      four simple and rapid steps. The ultrathin Au nanowires have a one-dimensional
      structure and were easily grafted with an abundant amount of L-Cys for the
      enrichment of glycopeptides. After the GO-Fe3O4/SiO2/AuNWs/L-Cys composites were
      applied to glycopeptide enrichment, 26 glycopeptides from a human IgG digest
      could be identified, with a detection limit as low as 10 fmol. Due to the
      abundant amount of grafted L-Cys, the composites also showed a large binding
      capacity (150 MUg mg-1). Furthermore, the composites were applied for the
      analysis of real biological samples. A total of 793 glycopeptides from 467
      glycoproteins were identified in three replicate analyses of 40 MUg of mouse
      liver proteins. The results demonstrated the great potential of GO
      Fe3O4/SiO2/AuNWs/L-Cys composites for the analysis of glycoproteins.

PMID- 28433059
TI  - An entropy-driven signal amplifying strategy for real-time monitoring of DNA
      methylation process and high-throughput screening of methyltransferase
      inhibitors.
AB  - Based on the entropy-driven toehold-mediated hairpin displacement (ETHDA), a
      facile and sensitive one-step fluorescence sensing platform has been proposed for
      the evaluation DNA methylation process catalyzed by methyltransferase (MTase). In
      this designed system, a hairpin probe is methylated by DNA adenine methylation
      (Dam) MTase and cleaved by DpnI endonuclease successively, liberating a catalyzer
      strand to initiate the signal amplification. The fluorescence intensity is
      increasing upon the catalyzer strand triggered circulating procedure of the ETHDA
      process. It is proved that the proposed biosensor is free of intricate procedures
      and avoids the interference of added amplification enzymes. According to the
      obtained result, the novel assay is exceedingly sensitive and selective in MTase
      detection with a low detection limit of 0.01 U mL-1 and a wide linear range of
      0.01-100 U mL-1, which indicatives of this method a great candidate for
      monitoring DNA methylation. Moreover, this biosensor can offer practical
      applications in the high-throughput screening of MTase inhibitors, of which
      broadens the potential in the clinical diagnostics and related biomedical
      research.

PMID- 28433060
TI  - Enhanced photoresponsive polyethyleneimine/citric acid co-carbonized dots for
      facile and selective sensing and intracellular imaging of cobalt ions at
      physiologic pH.
AB  - Whether as an important biological element or as a radioactive source/medicine,
      the monitoring of trace levels of cobalt ions (Co) has become a non-negligible
      factor for human health and green environment. Current technologies for the
      detection of Co are cost-expensive and time-consuming, and require cumbersome
      sample pretreatment process. Herein a novel sensing platform has been developed
      for Co detection based on the quenching of the enhanced fluorescence signal of
      polyamine functionalized C-dots. Amine groups at the surface of the C-dots can
      capture Zn2+/Cd2+ to form coordination compound, which can inhibit the
      photoinduced electron transfer pathways of C-dots and then induce the
      fluorescence enhancement of the C-dots by ~80% margin. Also, Co interacts with
      these amine groups to form an absorbent complex, which can strongly quench the
      enhanced fluorescence of C-dots via an inner filter effect. This C-dots-based
      probe showed a wide linear response to Co with a concentration ranging from 0.012
      to 12 MUM, and a detection limit of 8.0 nM and RSD of 5.7% (n = 5).
      Significantly, the C-Dots exhibit excellent properties, such as negligible
      cytotoxicity, excellent biocompatibility, low-cost and high photostability, etc.,
      which make C-dots favorable for label-free monitoring of Co and then successfully
      applied to the confocal imaging of intracellular Co.

PMID- 28433061
TI  - Graphene-coated polymeric anion exchangers for ion chromatography.
AB  - Carbonaceous stationary phases have gained much attention for their peculiar
      selectivity and robustness. Herein we report the fabrication and application of a
      graphene-coated polymeric stationary phase for anion exchange chromatography. The
      graphene-coated particles were fabricated by a facile evaporation-reduction
      method. These hydrophilic particles were proven appropriate substrates for
      grafting of hyperbranched condensation polymers (HBCPs) to make pellicular anion
      exchangers. The new phase was characterized by zeta potentials, Fourier transform
      infrared spectroscopy, thermogravimetry and scanning electron microscope. Frontal
      displacement chromatography showed that the capacities of the anion exchangers
      were tuned by both graphene amount and HBCPs layer count. The chromatographic
      performance of graphene-coated anion exchangers was demonstrated with separation
      of inorganic anions, organic acids, carbohydrates and amino acids. Good
      reproducibility was obtained by consecutive injections, indicating high chemical
      stability of the coating.

PMID- 28433063
TI  - Welcome, Dr. Brennan, to the National Library of Medicine!

PMID- 28433062
TI  - Electrospun Nafion-Polyacrylonitrile nanofibers as an ion exchange ultrathin
      layer chromatographic stationary phase.
AB  - An ion-exchange method to separate charged biomolecules on ultrathin layer
      chromatographic (UTLC) plates using electrospun Nafion-Polyacrylonitrile (PAN)
      nanofibers as the stationary phase is described. Sulfonate groups on Nafion
      provide the ion-exchange sites. The addition of PAN (a higher molecular weight
      polymer than Nafion) was used to facilitate the nanofiber formation process using
      electrospinning. Electrospinning parameters and separation conditions were
      optimized using fractional factorial design and response surface methodology.
      Nafion-PAN nanofibers containing 45% (w/w) Nafion with 0.407 mmol/g of SO3H group
      and 16.0 mmol/g of fluorine as an ion exchange stationary phase for UTLC were
      evaluated using the separations of amino acids and proteins, followed by
      visualizations using ninhydrin and fluorescamine, respectively. The electrospun
      Nafion-PAN plates showed high chemical stability under various mobile phase
      conditions. Mobile phase velocity decreased with the addition of Nafion into the
      electrospinning solutions. The sources of band broadening of analyte spots were
      investigated. The separation of amino acids showed high selectivity and
      separation efficiency. The separation of four proteins demonstrated the
      feasibility of Nafion-PAN UTLC for separating large biomolecules.

PMID- 28433064
TI  - Resilience.
AB  - Every child is a unique individual. This individuality is evident in children
      exposed to psychosocial trauma or adverse childhood experiences. There exists
      wide variation in the way children respond to toxic stressors in their lives.
      Some children appear to be relatively unaffected, while others develop a variety
      of psychological, behavioral, and physical consequences. What is the explanation
      for this phenomenon? Resiliency has been suggested to explain this variation in
      pathology expressions in trauma-exposed children. It is vital for pediatric nurse
      practitioners to understand the concept of resilience. This continuing education
      offering will define concepts of resilience and stress, explore the neurobiology
      of resilience, and examine interventions that promote resilience in children.

PMID- 28433065
TI  - Practice Guideline: Contraception for Adolescents with Chronic Illness.

PMID- 28433066
TI  - Erratum.

PMID- 28433067
TI  - Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by
      targeting basal autophagy and enhancing apoptosis.
AB  - Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are
      suggested to have potential anticancer properties. in the present study, we
      investigated the effects of CQ and HCQ on cell growth of bladder cancer with
      emphasis on autophagy inhibition and apoptosis induction in vitro. The results
      showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell
      lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion,
      especially in advanced bladder cancer cell lines (5637 and T24) compared to
      immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines
      (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly
      decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As
      human bladder cancer tumor exhibits high basal level of autophagic activities, we
      detected the autophagic flux in cells treated with CQ and HCQ, showing an
      alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer
      cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase
      3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP),
      caspase 3, and DNA fragmentation. Given these results, targeting autophagy with
      CQ and HCQ represents an effective cancer therapeutic strategy against human
      bladder cancer.

PMID- 28433068
TI  - The role of interleukin-1beta and extracellular signal-regulated kinase 1/2 in
      glucose-stimulated insulin secretion.
AB  - Glucose-stimulated insulin secretion (GSIS) is one of the important physiological
      characteristics of islet beta cells, and extracellular-regulated protein kinase
      1/2 (ERK1/2) is an important member of the mitogen-activated protein kinase
      family that regulates this process. The inflammatory cytokine interleukin (IL)
      1beta can inhibit the insulin secretion of pancreatic beta cells, but the exact
      mechanism is unclear. This study was designed to investigate the inhibitory
      effect of IL-1beta on GSIS in betaTC-6 cells and its relation with the ERK1/2
      signal transduction pathway. beta-TC6 cells were cultured and stimulated with
      0mM, 1.38mM, or 5.5mM glucose. In addition, GSIS in beta-TC6 cells was blocked by
      IL-1beta at concentrations of 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL. After glucose
      stimulation and IL-1beta intervention, the insulin level in the cell supernatant
      was detected by radioimmunoassay, and the phosphorylation level of ERK1/2 was
      detected by western blotting assay. The insulin level in the 1.38mM glucose group
      was 108.52 +/- 5.94 uIU/mL, which was significantly higher than the 0mM and 5.5mM
      glucose groups (p < 0.05). Compared with the 0mM glucose group, the level of
      ERK1/2 phosphorylation was increased in the 1.38mM and 5.5mM glucose groups.
      After intervention by 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL IL-1beta, the level of
      ERK1/2 phosphorylation induced by 1.38mM glucose stimulation decreased in a dose
      dependent manner, and the insulin level correspondingly decreased. IL-1beta can
      inhibit GSIS in betaTC-6 cells, which is related to its inhibition of the
      phosphorylation of ERK1/2.

PMID- 28433069
TI  - Assessment of therapeutic effect of human choriogonadotropin in a chemical
      cystitis model.
AB  - In this study, female rats induced with chemical cystitis were administered the
      hormone human choriogonadotropin (HCG), and it was aimed to reveal the usefulness
      of HCG in the treatment of interstitial cystitis/bladder pain syndrome. The
      materials for this study were 32 Wistar albino female rats. The study groups were
      formed as follows: the cystitis group (Group 1), the cystitis + HCG protection
      group (Group 2), the cystitis + HCG treatment group (Group 3), and the control
      group (Group 4), with eight rats in each group. In this study, blood and urine
      samples were taken from the rats, they were euthanized, and their bladders were
      removed for glutathione, malondialdehyde, tumor necrosis factor alpha, and
      interferon gamma measurements. It was observed that tissue damage in Group 2 was
      lower than that in the other two groups. Glutathione levels in Groups 2 and 4
      were significantly higher than in Groups 1 and 3 (p = 0.01). Malondialdehyde
      levels of Groups 2 and 4 were significantly lower than the values in Groups 1 and
      3 (p < 0.001). When the cystitis groups were compared in terms of their
      interferon gamma and tumor necrosis factor alpha levels, the lowest interferon
      gamma and tumor necrosis factor alpha levels were detected in Group 3. It was
      found that HCG has positive effects on experimental cystitis in rats. This study
      revealed that HCG should be researched as a therapeutic agent and formed a step
      for studies to be carried out on this subject.

PMID- 28433070
TI  - Effects of nicorandil on renal function and histopathology in rats with partial
      unilateral ureteral obstruction.
AB  - To evaluate the effects of nicorandil in a rat kidney model of partial unilateral
      ureteral obstruction (PUUO). Thirty male rats were randomly divided into three
      groups as follows: (1) Group 1 (Sham-control), ureters of the rats were
      manipulated but not ligated; (2) Group 2 (PUUO-untreated), PUUO was performed
      with two-thirds of the left ureter embedded in the psoas muscle; and (3) Group 3
      (PUUO-nicorandil treated). After PUUO was established, nicorandil (15 mg/kg/day)
      was administered by gastric lavage for 21 days to determine its effects on PUUO
      induced histopathological-, functional-, and oxidative stress-induced changes.
      The serum levels of blood urea nitrogen and creatinine were reduced in Group 3.
      The level of urinary albumin and the ratio of urinary protein/creatinine were
      increased in the kidneys of Group 2 but decreased in Group 3. Malondialdehyde
      value was decreased in Group 3 compared with Group 2. Antioxidant enzyme
      activities (catalase, superoxide dismutase, and glutathione peroxidase) were
      decreased in Group 2. Nicorandil treatment caused an increase in these enzyme
      activities. In Group 3, leukocyte infiltration and tubular dilatation were
      significantly reduced. Other parameters, such as degeneration of tubular
      epithelium and fibrosis, also showed a marked improvement in Group 3. Expression
      of inducible nitric oxide synthase in Group 2 and expression of endothelial
      nitric oxide synthase in Group 3 were significantly elevated. Nicorandil can
      inhibit renal tubular damage and tubulointerstitial fibrosis by reducing the
      effects of oxidative stress after PUUO.

PMID- 28433071
TI  - Association between the eruption of the third molar and caries and periodontitis
      distal to the second molars in elderly patients.
AB  - The objective of this study was to verify whether caries and periodontal
      diseases, when present on the distal surface of the second molars (M2s), are
      associated with the eruption of the third molars (M3s). In this split-mouth
      study, we evaluated 70 elderly patients with unilateral maxillary or mandibular
      M3s who presented to the outpatient clinics of two hospitals. Patients underwent
      comprehensive oral examinations and radiographical measurements, and we assessed
      the outcomes of periodontal disease and caries. Periodontal measurements included
      plaque index, bleeding on probing, and periodontal probing pocket depth (PD).
      Moreover, caries were assessed through visual-tactile examination and
      radiography. We performed the chi2 test to determine factors associated with M3
      and non-M3 outcomes. Eighty-one unilateral erupted M3s were observed in the study
      patients. Both the distobuccal region (p<0.0001) and the distolingual region
      (p=0.006) had a higher PD on the nonextraction side than the extraction side, and
      the caries rate was significantly higher on the nonextraction side than on the
      extraction side (p <0.0001 on M2 with caries and p=0.003 on M2 with distal
      caries). M3 eruption, at the same or different occlusal plane levels of M2, is a
      risk factor for periodontal diseases and caries in M2s in elderly patients. M3s
      may continue to negatively impact dental health well into later life.

PMID- 28433072
TI  - Correlations of dietary energy and protein intakes with renal function impairment
      in chronic kidney disease patients with or without diabetes.
AB  - Dietary energy and protein intake can affect progression of chronic kidney
      disease (CKD). CKD complicated with diabetes is often associated with a decline
      in renal function. We investigated the relative importance of dietary energy
      intake (DEI) and dietary protein intake (DPI) to renal function indicators in
      nondiabetic and diabetic CKD patients. A total of 539 Stage 3-5 CKD patients
      [estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2 using the
      Modification of Diet in Renal Disease equation] with or without diabetes were
      recruited from outpatient clinics of Nephrology and Nutrition in a medical center
      in Taiwan. Appropriateness of DEI and DPI was used to subcategorize CKD patients
      into four groups:(1) kidney diet (KD) A (KD-A), the most appropriate diet, was
      characterized by low DPI and adequate DEI; (2) KD-B, low DPI and inadequate DEI;
      (3) KD-C, excess DPI and adequate DEI; and (4) KD-D, the least appropriate diet,
      excess DPI and inadequate DEI. Inadequate DEI was defined as a ratio of actual
      intake/recommended intake less than 90% and adequate DEI as over 90%. Low DPI was
      defined as less than 110% of recommended intake and excessive when over 110%.
      Outcome measured was eGFR. In both groups of CKD patients, DEI was significantly
      lower (p<0.001) and DPI higher (p=0.002) than recommended levels. However, only
      in the nondiabetic CKD patients were KD-C and KD-D significantly correlated with
      reduced eGFR compared with KD-A at increments of -5.63 mL/min/1.73 m2 (p = 0.029)
      and -7.72 mL/min/1.73 m2 (p=0.015). In conclusion, inadequate energy and
      excessive protein intakes appear to correlate with poorer renal function in
      nondiabetic CKD patients. Patients with advanced CKD are in need of counseling by
      dietitians to improve adherence to diets.

PMID- 28433073
TI  - Neurocognitive function in clinically stable individuals with long-term bipolar I
      disorder: Comparisons with schizophrenia patients and controls.
AB  - This study compared the levels of the five domains of neurocognitive function
      executive function, attention, memory, verbal comprehension, and perceptual
      organization-among clinically stable individuals with long-term bipolar I
      disorder, individuals with long-term schizophrenia, and a group of controls. We
      recruited a total of 93 clinically stable individuals with bipolar I disorder, 94
      individuals with schizophrenia, and 106 controls in this study. Their
      neurocognitive function was measured using a series of neurocognitive function
      tests: the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), Line
      Cancellation Test, Visual Form Discrimination, Controlled Oral Word Association
      Test, Wisconsin Card Sorting Test, Continuous Performance Task, and Wechsler
      Memory Scale-Third Edition. Neurocognitive function was compared among the three
      groups through a multivariate analysis of variance. The results indicated that
      when the effect of age was controlled, clinically stable individuals with bipolar
      I disorder and those with schizophrenia demonstrated poor neurocognitive function
      on all tests except for the WAIS-III Similarity and Information and the Line
      Cancellation Test. The individuals with bipolar I disorder had similar levels of
      neurocognitive function compared with the schizophrenia group, but higher levels
      of neurocognitive function on the WAIS-III Comprehension, Controlled Oral Word
      Association Test, and Wechsler Memory Scale-Third Edition Auditory Immediate and
      Delayed Index and Visual Immediate and Delayed Index. The conclusions of this
      study suggest that compared with controls, individuals with long-term bipolar I
      disorder and those with long-term schizophrenia have poorer neurocognitive
      function, even when clinically stable. Individuals with long-term bipolar I
      disorder and those with long-term schizophrenia have similar levels of deficits
      in several domains of neurocognitive function.

PMID- 28433074
TI  - Nodular fasciitis causing progressive limitation of knee flexion in a marathon
      runner: Imaging with ultrasound and magnetic resonance.

PMID- 28433075
TI  - Upper gastrointestinal bleeding caused by Strongyloides stercoralis: Highlighting
      a neglected parasitic infection.

PMID- 28433076
TI  - Identification of NTRK3 Fusions in Childhood Melanocytic Neoplasms.
AB  - Spitzoid neoplasms are a distinct group of melanocytic tumors. Genetically, they
      lack mutations in common melanoma-associated oncogenes. Recent studies have shown
      that spitzoid tumors may contain a variety of kinase fusions, including ROS1,
      NTRK1, ALK, BRAF, and RET fusions. We report herein the discovery of recurrent
      NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or
      atypical features, based on genome-wide copy number analysis by single-nucleotide
      polymorphism array, which showed intragenic copy number changes in NTRK3. Break
      apart fluorescence in situ hybridization confirmed the presence of NTRK3
      rearrangement, and a novel MYO5A-NTRK3 transcript, representing an in-frame
      fusion of MYO5A exon 32 to NTRK3 exon 12, was identified using a rapid
      amplification of cDNA ends-based anchored multiplex PCR assay followed by next
      generation sequencing. The predicted MYO5A-NTRK3 fusion protein consists of
      several N-terminal coiled-coil protein dimerization motifs encoded by MYO5A and C
      terminal tyrosine kinase domain encoded by NTRK3, which is consistent with the
      prototypical structure of TRK oncogenic fusions. Our study also demonstrates how
      array-based copy number analysis can be useful in discovering gene fusions
      associated with unbalanced genomic aberrations flanking the fusion points. Our
      findings add another potentially targetable kinase fusion to the list of
      oncogenic fusions in melanocytic tumors.

PMID- 28433077
TI  - Development and Clinical Utility of a Blood-Based Test Service for the Rapid
      Identification of Actionable Mutations in Non-Small Cell Lung Carcinoma.
AB  - Nearly 80% of cancer patients do not have genetic mutation results available at
      initial oncology consultation; up to 25% of patients begin treatment before
      receiving their results. These factors hinder the ability to pursue optimal
      treatment strategies. This study validates a blood-based genome-testing service
      that provides accurate results within 72 hours. We focused on targetable variants
      in advanced non-small cell lung carcinoma-epidermal growth factor receptor gene
      (EGFR) variant L858R, exon 19 deletion (DeltaE746-A750), and T790M; GTPase
      Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated
      protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EML4-ALK)
      transcripts 1/2/3. Test development included method and clinical validation using
      samples from donors with (n = 219) or without (n = 30) cancer. Clinical
      sensitivity and specificity for each variant ranged from 78.6% to 100% and 94.2%
      to 100%, respectively. We also report on 1643 non-small cell lung carcinoma
      samples processed in our CLIA-certified laboratory. Mutation results were
      available within 72 hours for 94% of the tests evaluated. We detected 10.5%
      mutations for EGFR sensitizing (n = 2801 samples tested), 13.8% mutations for
      EGFR resistance (n = 1055), 13.2% mutations in KRAS (n = 3477), and 2% mutations
      for EML4-ALK fusion (n = 304). This rapid, highly sensitive, and actionable blood
      based assay service expands testing options and supports faster treatment
      decisions.

PMID- 28433078
TI  - Haplotype Counting for Sensitive Chimerism Testing: Potential for Early Leukemia
      Relapse Detection.
AB  - Fields of forensics, transplantation, and paternity rely on human identity
      testing. Currently, this is accomplished through amplification of microsatellites
      followed by capillary electrophoresis. An alternative and theoretically better
      approach uses multiple single-nucleotide polymorphisms located within a small
      region of DNA, a method we initially developed using HLA-A and called haplotype
      counting. Herein, we validated seven additional polymorphic loci, sequenced a
      total of 45 individuals from three of the 1000 Genomes populations (15 from
      each), and determined the number of haplotypes, heterozygosity, and polymorphic
      information content for each locus. In addition, we developed a multiplex PCR
      that amplifies five of these loci simultaneously. Using this strategy with a
      small cohort of leukemic patients who underwent allogeneic bone marrow
      transplantation, we first attempted to define a threshold (0.26% recipient) by
      examining seven patients who tested all donor and did not relapse. Although this
      initial threshold will need to be confirmed in a larger cohort, we detected
      increased recipient DNA above this threshold 90 to 145 days earlier than
      microsatellite positivity, and 127 to 142 days before clinical relapse in four of
      eight patients (50%). Haplotype counting using these novel loci may be useful for
      ultrasensitive detection in fields such as bone marrow transplantation, solid
      organ transplant rejection, patient identification, and forensics.

PMID- 28433080
TI  - Correction.

PMID- 28433081
TI  - Correction.

PMID- 28433082
TI  - Gender: An Issue, Not the Issue.

PMID- 28433079
TI  - Utilization of Whole-Exome Next-Generation Sequencing Variant Read Frequency for
      Detection of Lesion-Specific, Somatic Loss of Heterozygosity in a
      Neurofibromatosis Type 1 Cohort with Tibial Pseudarthrosis.
AB  - A subset of neurofibromatosis type 1 patients develop tibial dysplasia, which can
      lead to pseudarthrosis. The tissue from the tibial pseudarthrosis region commonly
      has a somatic second hit in NF1: single-nucleotide variants, small deletions, or
      loss of heterozygosity (LOH). We used exome next-generation sequencing (NGS)
      variant frequency data (allelic imbalance analysis) to detect somatic LOH in
      pseudarthrosis tissue from three individuals with clinically and diagnostically
      confirmed neurofibromatosis type 1, and verified the results with microarray. The
      variant files were parsed and plotted using python scripts, and the NGS variant
      frequencies between the affected tissue and blood sample were compared.
      Individuals without somatic single-nucleotide variants or small
      insertions/deletions were tested for somatic LOH using the NGS variant allele
      frequencies. One individual's NGS data indicated no LOH in chromosome 17. The
      other two individuals demonstrated somatic LOH inclusive of NF1: one had an LOH
      region of approximately one million bases and Contra (NGS copy number program)
      indicated a somatic deletion and the other individual had LOH for most of
      chromosome 17q and Contra indicated no copy number change (microarray data
      verified this sample as copy neutral somatic LOH). Both LOH and copy number
      variation detected by NGS data correlated with microarray data, demonstrating the
      somatic LOH second hit can be detected directly from the NGS data.

PMID- 28433083
TI  - Getting Write Into Therapy.

PMID- 28433084
TI  - Born at the Right Time: Examining the Role of Parental Age on Child
      Psychopathology.

PMID- 28433085
TI  - ROC on With ASEBA and the Attention Problems.

PMID- 28433086
TI  - Intergenerational Transmission of Maternal Childhood Maltreatment Exposure:
      Implications for Fetal Brain Development.
AB  - OBJECTIVE: Growing evidence suggests the deleterious consequences of exposure to
      childhood maltreatment (CM) not only might endure over the exposed individual's
      lifespan but also might be transmitted across generations. The time windows,
      mechanisms, and targets of such intergenerational transmission are poorly
      understood. The prevailing paradigm posits that mother-to-child transmission of
      the effects of maternal CM likely occurs after her child's birth. The authors
      seek to extend this paradigm and advance a transdisciplinary framework that
      integrates the concepts of biological embedding of life experiences and fetal
      origins of health and disease risk. METHOD: The authors posit that the period of
      embryonic and fetal life represents a particularly sensitive time for
      intergenerational transmission; that the developing brain represents a target of
      particular interest; and that stress-sensitive maternal-placental-fetal
      biological (endocrine, immune) pathways represent leading candidate mechanisms of
      interest. RESULTS: The plausibility of this model is supported by theoretical
      considerations and empirical findings in humans and animals. The authors
      synthesize several research areas and identify important knowledge gaps that
      might warrant further study. CONCLUSION: The scientific and public health
      relevance of this effort relates to achieving a better understanding of the
      "when," "what," and "how" of intergenerational transmission of CM, with
      implications for early identification of risk, prevention, and intervention.

PMID- 28433087
TI  - Paternal Age Alters Social Development in Offspring.
AB  - OBJECTIVE: Advanced paternal age (APA) at conception has been linked with autism
      and schizophrenia in offspring, neurodevelopmental disorders that affect social
      functioning. The current study explored the effects of paternal age on social
      development in the general population. METHOD: We used multilevel growth modeling
      to investigate APA effects on socioemotional development from early childhood
      until adolescence, as measured by the Strengths and Difficulties Questionnaire
      (SDQ) in the Twins Early Development Study (TEDS) sample. We also investigated
      genetic and environmental underpinnings of the paternal age effects on
      development, using the Additive genetics, Common environment, unique Environment
      (ACE) and gene-environment (GxE) models. RESULTS: In the general population, both
      very young and advanced paternal ages were associated with altered trajectory of
      social development (intercept: p = .01; slope: p = .03). No other behavioral
      domain was affected by either young or advanced age at fatherhood, suggesting
      specificity of paternal age effects. Increased importance of genetic factors in
      social development was recorded in the offspring of older but not very young
      fathers, suggesting distinct underpinnings of the paternal age effects at these
      two extremes. CONCLUSION: Our findings highlight that the APA-related deficits
      that lead to autism and schizophrenia are likely continuously distributed in the
      population.

PMID- 28433088
TI  - Parental Age and Offspring Psychopathology in the Philadelphia Neurodevelopmental
      Cohort.
AB  - OBJECTIVE: Increasing evidence implicates advanced paternal age at offspring
      birth in neuropsychiatric disorders. Advanced maternal age has also been
      associated with schizophrenia and other neurodevelopmental disorders, whereas
      younger maternal age has been linked with behavioral disorders. Few studies have
      considered the specificity of the associations with respect to comorbidity. In
      addition, most prior studies have been conducted in clinical samples or
      registries that may reflect more severe forms of psychopathology. The aim of this
      research is to examine the independent and joint associations of maternal and
      paternal age with specific subtypes of psychopathology in offspring in a
      pediatric sample of adolescents with emergent psychiatric syndromes. METHOD: A
      total of 8,725 youths (aged 8-21 years) from the Philadelphia Neurodevelopmental
      Cohort were included in the analyses. Logistic regression models with parental
      age predicting offspring psychopathology were adjusted for sociodemographic
      factors and comorbid disorders. RESULTS: We found that younger parental ages were
      generally associated with increased rates of offspring psychopathology. After
      controlling for sociodemographic characteristics and comorbidity, both younger
      maternal and paternal ages were associated with behavior syndromes and psychosis
      in youth, whereas advanced paternal age was associated with pervasive
      developmental disorders/autism spectrum disorder (PDD/ASD). CONCLUSION: These
      findings suggest that both younger and older parental age at birth are associated
      with specific forms of psychopathology in offspring. The persistence of the
      influence of parental age after control for demographic factors and an index of
      social environment suggests that additional explanations for these findings
      should be examined in future studies.

PMID- 28433089
TI  - Accuracy of Achenbach Scales in the Screening of Attention-Deficit/Hyperactivity
      Disorder in a Community Mental Health Clinic.
AB  - OBJECTIVE: To use receiver-operating characteristics analysis to identify
      multilevel diagnostic likelihood ratios and provide a framework for the diagnosis
      of attention-deficit/hyperactivity disorder (ADHD) in children (5-10 years old)
      and adolescents (11-18 years old) in an outpatient setting. METHOD: Caregiver,
      teacher, and youth reports from the Achenbach System of Empirically Based
      Assessment (ASEBA) were obtained for 299 children and 321 adolescents with
      multiple imputation of missing data. The reference standard was diagnosis of ADHD
      based on case history and a semistructured diagnostic interview masked to the
      ASEBA measurements. RESULTS: In children, caregiver-reported Attention Problems
      (area under the curve [AUC] = 0.74) outperformed all other subscales of the
      caregiver and teacher measures (AUCs <= 0.72). In the older sample, caregiver-
      and teacher-reported Attention Problems (caregiver AUC = 0.73; teacher AUC =
      0.61) were best at identifying ADHD. Inclusion of caregiver and teacher reports
      significantly (p < .001 for all comparisons) increased prediction of ADHD
      diagnosis, whereas youth self-report did not. CONCLUSION: Caregiver-reported
      Attention Problems were more useful than teacher-reports and self-report in
      identifying ADHD. Combining caregiver and teacher reports improved
      identification. Multilevel likelihood ratios are provided to facilitate routine
      clinical use.

PMID- 28433090
TI  - Neural Biomarker and Early Temperament Predict Increased Internalizing Symptoms
      After a Natural Disaster.
AB  - OBJECTIVE: Although most people will experience a traumatic event at some point
      in their life, only some will develop significant psychological symptoms in the
      aftermath. In the current study, we use a preexisting longitudinal study located
      in Long Island to examine the impact of Hurricane Sandy on internalizing symptoms
      in a large sample of children. We focused on temperamental fear and a biomarker
      of risk for anxiety, the error-related negativity (ERN). The ERN is a negative
      deflection in the event-related potential (ERP) occurring when individuals make
      mistakes and is increased in anxious individuals. METHOD: The final sample
      consisted of 223 children who had undergone an observational assessment of fear
      at age 3 years and an electroencephalogram assessment of the ERN at age 6 years.
      At the age 9 year assessment, internalizing symptoms were assessed, and then
      again after the hurricane (~65 weeks later). RESULTS: A significant three-way
      interaction among fearfulness, hurricane stressors, and the ERN in predicting
      posthurricane increases in internalizing symptoms suggested that children who
      were high in fear at age 3 years and experienced elevated hurricane stressors
      were characterized by subsequent increases in internalizing symptoms, but only
      when they were also characterized by an increased ERN at age 6 years. CONCLUSION:
      These findings support a diathesis-stress model, suggesting that early
      temperament and prestressor biological markers confer risk for increased
      psychological symptoms following environmental stressors.

PMID- 28433091
TI  - Internet-Delivered Parenting Program for Prevention and Early Intervention of
      Anxiety Problems in Young Children: Randomized Controlled Trial.
AB  - OBJECTIVE: The Cool Little Kids parenting group program is an effective
      intervention for preventing anxiety disorders in young children who are at risk
      because of inhibited temperament. The program has six group sessions delivered by
      trained psychologists to parents of 3- to 6-year-old children. An online
      adaptation (Cool Little Kids Online) has been developed to overcome barriers to
      its wide dissemination in the community. This study tested the efficacy of Cool
      Little Kids Online in a randomized controlled trial. METHOD: A total of 433
      parents of a child aged 3 to 6 years with an inhibited temperament were
      randomized to the online parenting program or to a 24-week waitlist. The online
      program has 8 interactive modules providing strategies that parents can implement
      with their child to manage their child's avoidant coping, reduce parental
      overprotection, and encourage child independence. Parents were provided telephone
      consultation support with a psychologist when requested. Parents completed self
      report questionnaires at baseline and at 12 and 24 weeks after baseline. RESULTS:
      The intervention group showed significantly greater improvement over time in
      child anxiety symptoms compared to the control group (d = 0.38). The intervention
      group also showed greater reductions in anxiety life interference (ds = 0.33
      0.35) and lower rates of anxiety disorders than the control group (40% versus
      54%), but there were minimal effects on broader internalizing symptoms or
      overprotective parenting. CONCLUSION: Results provide empirical support for the
      efficacy of online delivery of the Cool Little Kids program. Online dissemination
      may improve access to an evidence-based prevention program for child anxiety
      disorders. Clinical trial registration information-Randomised Controlled Trial of
      Cool Little Kids Online: A Parenting Program to Prevent Anxiety Problems in Young
      Children; http://www.anzctr.org.au/; 12615000217505.

PMID- 28433094
TI  - Trouble.

PMID- 28433092
TI  - Behavioral and Neural Sustained Attention Deficits in Disruptive Mood
      Dysregulation Disorder and Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: Disruptive mood dysregulation disorder (DMDD), characterized by severe
      irritability, and attention-deficit/hyperactivity disorder (ADHD) are highly
      comorbid. This is the first study to characterize neural and behavioral
      similarities and differences in attentional functioning across these disorders.
      METHOD: Twenty-seven healthy volunteers, 31 patients with DMDD, and 25 patients
      with ADHD (8 to 18 years old) completed a functional magnetic resonance imaging
      attention task. Group differences in intra-subject variability in reaction time
      (RT) were examined. The present functional magnetic resonance imaging analytic
      approach precisely quantified trial-wise associations between RT and brain
      activity. RESULTS: Group differences manifested in the relation between RT and
      brain activity (all regions: p < .01, F > 2.54, partial eta-squared [etap2] >
      0.06). Patients with DMDD showed specific alterations in the right paracentral
      lobule, superior parietal lobule, fusiform gyrus, and cerebellar culmen. In
      contrast, patients with DMDD and those with ADHD exhibited blunted compensatory
      increases in activity on long RT trials. In addition, youth with DMDD exhibited
      increased activity in the postcentral gyrus, medial frontal gyrus, and cerebellar
      tonsil and declive (all regions: p < .05, F > 2.46, etap2 > 0.06). Groups in the
      imaging sample did not differ significantly in intra-subject variability in RT
      (F2,79 = 2.664, p = .076, etap2 = 0.063), although intra-subject variability in
      RT was significantly increased in youth with DMDD and ADHD when including those
      not meeting strict motion and accuracy criteria for imaging analysis (F2,96 =
      4.283, p = .017, etap2 = 0.083). CONCLUSION: Patients with DMDD exhibited
      specific alterations in the relation between pre-stimulus brain activity and RT.
      Patients with DMDD and those with ADHD exhibited similar blunting of compensatory
      neural activity in frontal, parietal, and other regions. In addition, patients
      with DMDD showed increased RT variability compared with healthy youth. This work
      is the first to identify common and unique behavioral and neural signatures of
      DMDD and ADHD.

PMID- 28433093
TI  - Impact of a Common Genetic Variation Associated With Putamen Volume on Neural
      Mechanisms of Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: In a recent genomewide association study of subcortical brain volumes,
      a common genetic variation at rs945270 was identified as having the strongest
      effect on putamen volume, a brain measurement linked to familial risk for
      attention-deficit/hyperactivity disorder (ADHD). To determine whether rs945270
      might be a genetic determinant of ADHD, its effects on ADHD-related symptoms and
      neural mechanisms of ADHD, such as response inhibition and reward sensitivity,
      were explored. METHOD: A large population sample of 1,834 14-year-old adolescents
      was used to test the effects of rs945270 on ADHD symptoms assessed through the
      Strengths and Difficulties Questionnaire and region-of-interest analyses of
      putamen activation by functional magnetic resonance imaging using the stop signal
      and monetary incentive delay tasks, assessing response inhibition and reward
      sensitivity, respectively. RESULTS: There was a significant link between rs945270
      and ADHD symptom scores, with the C allele associated with lower symptom scores,
      most notably hyperactivity. In addition, there were sex-specific effects of this
      variant on the brain. In boys, the C allele was associated with lower putamen
      activity during successful response inhibition, a brain response that was not
      associated with ADHD symptoms. In girls, putamen activation during reward
      anticipation increased with the number of C alleles, most significantly in the
      right putamen. Remarkably, right putamen activation during reward anticipation
      tended to negatively correlate with ADHD symptoms. CONCLUSION: These results
      indicate that rs945270 might contribute to the genetic risk of ADHD partly
      through its effects on hyperactivity and reward processing in girls.

PMID- 28433095
TI  - History of Wilson disease: a personal account.
AB  - This chapter focuses on the historic aspects of the development of much of our
      current knowledge of the diagnosis and treatment of Wilson disease. Included are
      descriptions of the clinical signs of neurologic and hepatic disease, the natural
      history of disease progression, studies of disease pathogenesis and a unique
      perspective on the development of diagnostic testing and pharmacological therapy.

PMID- 28433096
TI  - Wilson disease: neurologic features.
AB  - Wilson disease (WD) is a neurodegenerative disorder, which presents as a spectrum
      of neurologic manifestations that includes tremor, bradykinesia, rigidity,
      dystonia, chorea, dysarthria, and dysphagia, together with a combination of
      neurologic symptoms that can easily lead to misdiagnosis. An early diagnosis of
      WD, and appropriate anticopper treatment, usually leads to a marked improvement
      in patient health. Conversely, delayed diagnosis can result in persistent
      pathology, which, left untreated, can ultimately prove lethal. The aim of this
      chapter is to present a detailed description of the neurologic features of WD,
      including their evaluation, together with relevant ophthalmologic examinations,
      brain neuroimaging, and other laboratory measurements that show the extent of the
      involvement of the nervous system.

PMID- 28433097
TI  - Cognitive and psychiatric symptoms in Wilson disease.
AB  - Wilson disease - can present with such a variety of psychiatric and cognitive
      symptoms that it has been named the "great masquerader." Symptoms may include
      cognitive deficits, impairment of executive function, mood disturbance or
      psychosis. These impairments may occur in different stages of the disease and
      with varying intensity in individual patients. This chapter reviews the
      literature and authors' clinical experiences of the assessment, mechanism, and
      prevalence of cognitive and psychiatric pathology occurring in Wilson disease.
      Evidence of pharmacologic and nonpharmacologic treatments is also discussed.

PMID- 28433098
TI  - Wilson disease in children.
AB  - Wilson disease (WD) is an inherited disorder mainly of hepatocellular copper
      disposition, due to dysfunction of the Wilson ATPase, a P1B-ATPase encoded by the
      gene ATP7B. In children, as in older age brackets, clinical disease is highly
      diverse. Although hepatic disease is the common presentation in
      children/adolescents, neurologic, psychiatric, and hematologic clinical
      presentations do occur. Very young children may have clinically evident liver
      disease due to WD. Early diagnosis, preferably when the child/adolescent is
      asymptomatic, is most likely to result in near-normal longevity with generally
      good health so long as the patient tolerates effective medication, is adherent to
      the lifelong treatment regimen, and has consistent access to the medication.
      Apart from a lively index of clinical suspicion on the part of physicians,
      biochemical tests including liver tests, serum ceruloplasmin, and basal 24-hour
      urinary copper excretion and genotype determination are key to diagnosis. Oral
      chelation treatment remains central to medical management, although zinc appears
      to be an attractive option for the presymptomatic child. Pediatric patients
      presenting with Wilsonian fulminant hepatic failure must be differentiated from
      those with decompensated cirrhosis, since the latter may respond to intensive
      medical interventions and not require liver transplantation. Recently identified
      WD-mimic disorders reveal important aspects of WD pathogenesis.

PMID- 28433099
TI  - Other organ involvement and clinical aspects of Wilson disease.
AB  - Wilson disease (WD) is a rare disorder of copper metabolism that presents mainly
      with hepatic and neuropsychiatric features. Copper accumulates not only in the
      liver and brain, but also in other organs. Liver injury can also be the cause of
      secondary impairment of other tissues. Therefore, the clinical manifestation of
      WD may be renal, cardiac, skin, osteoarticular, or endocrinologic and include
      other organ disturbances. Renal abnormalities include tubular dysfunction (e.g.,
      renal tubular acidosis, aminoaciduria) and nephrolithiasis. Bone demineralization
      is a common manifestation in patients with WD. Cardiac injury may include
      arrhythmia, cardiomyopathy, and autonomic dysfunction. Different endocrine system
      manifestations, such as infertility or repeated miscarriages, growth and puberty
      disturbances, and hypoparathyroidism, are observed. Other important clinical
      aspects of WD include pancreas involvement, immunologic abnormalities, the
      presence of lipomas, and skin changes. Although other organ involvement is not
      common in WD and usually not severe, delayed diagnosis may lead to irreversible
      changes in organs and tissues. Therefore, awareness of other possible WD
      presentations is important in the differential diagnosis of WD.

PMID- 28433100
TI  - Diagnosis of Wilson disease.
AB  - Clinical presentation of Wilson disease can vary widely; therefore diagnosis is
      not always straightforward. Wilson disease is not just a disease of children and
      young adults, but may present at any age. The key features of Wilson disease are
      liver disease and cirrhosis, neuropsychiatric disturbances, Kayser-Fleischer
      rings, and acute episodes of hemolysis, often in association with acute liver
      failure. Diagnosis is particularly difficult in children and in adults presenting
      with active liver disease. None of the available laboratory tests is perfect and
      may not be specific for Wilson disease. A detailed neurologic examination is
      required for all cases. Neuroimaging and electrophysiologic methods are helpful.
      To overcome the diagnostic challenge, several clinical signs (Kayser-Fleischer
      rings, neurologic symptoms) and laboratory features (copper in serum, urine,
      liver; serum ceruloplasmin; genetic testing) are scored 0 (absent) to 2 (present)
      and the Leipzig score is calculated. If the score is >=4, the diagnosis of Wilson
      disease is very likely. For asymptomatic siblings of index patients, mutation
      analysis is the most reliable approach.

PMID- 28433101
TI  - Wilson disease - currently used anticopper therapy.
AB  - Wilson disease (WD) is a genetic disorder of copper metabolism that can be
      treated successfully with pharmacologic treatment. Two groups of drugs are
      currently used: chelators (e.g., d-penicillamine and trientine), which increase
      urinary copper excretion, and zinc salts, which inhibit copper absorption in the
      digestive tract. The mechanisms of action lead to a negative copper balance,
      stopping pathologic accumulation of copper in the tissues and clearing affected
      organs of copper overload. Due to a lack of prospective clinical trials, the use
      of drugs depends mainly on center experience and the accessibility in different
      countries or regions. This chapter presents the different reports and
      recommendations regarding WD treatment. In addition to the different expert
      opinions on pharmacologic agents, there are a few axioms regarding WD treatment:
      treatment should start immediately after diagnosis, even in clinically
      presymptomatic cases; the patient should be treated for life, making compliance a
      key factor in treatment success; and the treatment should be monitored regularly
      via liver and hematologic tests, neurologic examination, and copper metabolism,
      modifying the treatment accordingly. Other drugs proposed for WD treatment (e.g.,
      tetrathiomolybdate) are in clinical trials and lack current recommendations.
      Thus, only the currently available options for WD pharmacologic treatment are
      discussed.

PMID- 28433103
TI  - Liver transplantation for Wilson disease.
AB  - Liver transplantation (LT) is a life-saving and curative treatment for Wilson
      disease (WD), providing restoration of function of the liver and mitigation of
      portal hypertension. Indications for LT in patients with WD include acute liver
      failure or end-stage liver disease not treatable by medical therapy. LT is also
      used to treat hepatocellular carcinoma when it develops in patients with WD when
      tumor resection is not feasible. LT solely for neurologic or psychiatric WD
      remains controversial. Living liver donation as well as cadaveric orthotopic and
      auxiliary LT are options for transplantation for WD. Outcomes for LT for WD are
      excellent, and supportive measures while awaiting transplantation help bridge the
      patient to a more successful outcome. Future hepatocyte or stem cell
      transplantation may augment or supplant current LT for WD.

PMID- 28433104
TI  - Wilson disease: symptomatic liver therapy.
AB  - Wilson disease leads to symptomatic impairment of liver function or liver
      cirrhosis. Strict adherence to decoppering agents is essential in these patients.
      Secondary prevention of additional hepatic damage by avoidance of other toxic
      substances (e.g., alcohol, drugs) and sufficient calorie intake is recommended.
      Routine examinations in cirrhotic patients include screening for signs of portal
      hypertension (esophagus varices), development of ascites, and hepatic
      encephalopathy. Where varices are present, primary or secondary preventive
      interventions may include treatment with nonselective beta-blockers or variceal
      ligation, similar to the approach in patients with liver cirrhosis due to other
      etiologies. For patients presenting with ascites, diuretics are the treatment of
      choice. Spontaneous bacterial peritonitis can be diagnosed by paracentesis and
      should be treated with antibiotics. Liver cirrhosis can also lead to accumulation
      of neurotoxins causing hepatic encephalopathy. It is characterized by unspecific
      neuropsychiatric impairment and is treated with laxatives and nonresorbable
      antibiotics. The best prophylaxis is regular defecation. Patients with liver
      cirrhosis are susceptible for bacterial infections of any cause and sepsis is one
      of the leading causes of death in these patients. In advanced stages of cirrhosis
      renal function impairment is a common feature. The hepatorenal syndrome shows a
      high mortality. Where Wilson disease patients have decompensated liver cirrhosis,
      liver transplantation should be evaluated.

PMID- 28433105
TI  - Symptomatic treatment of neurologic symptoms in Wilson disease.
AB  - Wilson disease (WD) is a potentially treatable neurodegenerative disorder. In the
      majority of cases, treatment with drugs that induce a negative copper balance
      (usually chelators or zinc salts) leads to improvements in liver function and
      neurologic signs. However, some patients show severe neurologic symptoms at
      diagnosis, such as tremor, dystonia, parkinsonism, and chorea. In this patient
      group, some neurologic deficits may persist despite adequate treatment, and
      further neurologic deterioration may be observed after treatment initiation. Such
      patients may require additional treatment to alleviate neurologic symptoms. Apart
      from general recommendations for WD anticopper treatment, there are currently no
      guidelines for managing neurologic symptoms in WD. The aim of this chapter is to
      summarize possible treatments of neurologic symptoms in WD based on the presently
      available medical literature.

PMID- 28433102
TI  - The genetics of Wilson disease.
AB  - Wilson disease (WD) is an autosomal-recessive disorder of hepatocellular copper
      deposition caused by pathogenic variants in the copper-transporting gene, ATP7B.
      Early detection and treatment are critical to prevent lifelong neuropsychiatric,
      hepatic, and systemic disabilities. Due to the marked heterogeneity in age of
      onset and clinical presentation, the diagnosis of Wilson disease remains
      challenging to physicians today. Direct sequencing of the ATP7B gene is the most
      sensitive and widely used confirmatory testing method, and concurrent biochemical
      testing improves diagnostic accuracy. More than 600 pathogenic variants in ATP7B
      have been identified, with single-nucleotide missense and nonsense mutations
      being the most common, followed by insertions/deletions, and, rarely, splice site
      mutations. The prevalence of Wilson disease varies by geographic region, with
      higher frequency of certain mutations occurring in specific ethnic groups. Wilson
      disease has poor genotype-phenotype correlation, although a few possible
      modifiers have been proposed. Improving molecular genetic studies continue to
      advance our understanding of the pathogenesis, diagnosis, and screening for
      Wilson disease.

PMID- 28433106
TI  - Novel perspectives on Wilson disease treatment.
AB  - Wilson disease is an autosomal-recessive copper overload disorder causing hepatic
      and neurologic symptoms. Commonly used medical therapy shows satisfactory results
      with regard to hepatic disease but only limited effects in neurologically
      affected patients. In recent years several new therapy options have been
      developed, showing promising results that might improve the management of Wilson
      disease in the near future. Optimization of treatment regimens depending on
      biochemical response pattern seems worthwhile, especially in the decoppering
      phase of therapy. The chelator tetrathiomolybdate (TTM) is a promising therapy
      option, currently under clinical investigation. TTM is a fast-acting and very
      potent chelator and appears to be associated with early neurologic deterioration
      after initiation of therapy to a lower extent than the drugs currently used.
      Treatment with nonchelating drugs characterized by alternative modes of action is
      under investigation, but restricted to animal or in vitro studies to date. This
      includes basic research studies demonstrating proof of principle for successful
      cell or gene therapy in Wilson disease in order to restore sufficient biliary
      copper excretion, even before the onset of disease.

PMID- 28433107
TI  - Patient support groups in the management of Wilson disease.
AB  - Patient support groups serve an important function for those affected by a
      disease but especially for people with a rare disease. Because of the complexity
      of Wilson disease there are some unique and difficult problems faced by groups
      that advocate for these patients. We give a comparative overview of the
      differences between groups that support people with more common diseases and
      groups that serve the rare disease population. The history and current status of
      the Wilson Disease Association and other worldwide Wilson disease groups are
      described and information about other organizations that support Wilson disease
      in additional ways is explained. The specific challenges faced in the support of
      Wilson disease patients are outlined and possible solutions proposed. Drawing
      from experience in speaking with many patients, we discuss some of the most
      common questions that are asked by patients who are seeking a possible diagnosis
      or are already on treatment. There are many options for improving patient
      advocacy efforts in the future that we hope will be accomplished.

PMID- 28433108
TI  - Genetic and environmental modifiers of Wilson disease.
AB  - Wilson disease (WD) is characterized by remarkable variety in its phenotypic
      presentation. Patients with WD can present with hepatic, neurologic, and
      psychiatric symptoms combined in different and unpredictable ways. Importantly,
      no convincing phenotype-genotype correlation has ever been identified, opening
      the possibility that other genes, aside from ATPase copper-transporting beta
      (ATP7B), are involved in the pathogenesis of this condition. In addition,
      modifier genes, or genes that can affect the expression of other genes, may be
      involved. Clinical and basic science data indicate that environmental and dietary
      factors can potentially modify gene expression in WD and, consequently, its
      clinical presentation and course. In particular, previously studied genes include
      copper metabolism domain-containing 1 (COMMD1), antioxidant 1 copper chaperone
      (ATOX1), X-linked inhibitor of apoptosis (XIAP), apolipoprotein E (APOE),
      hemochromatosis (HFE), and 5,10-methylenetetrahydrofolate reductase (MTHFR).
      Dietary factors include iron and methyl group donors which could affect
      methionine metabolism and epigenetic mechanisms of gene expression regulation.
      Most of the work conducted in this field is in its initial stages but it has the
      potential to change the diagnosis and treatment of WD.

PMID- 28433109
TI  - Pathogenesis of Wilson disease.
AB  - Wilson disease is an autosomal-recessive disorder originating from a genetic
      defect in the copper-transporting ATPase ATP7B that is required for biliary
      copper secretion and loading of ceruloplasmin with copper. Impaired ATP7B
      function in Wilson disease results in excessive accumulation of copper in liver,
      brain, and other tissues. Toxic copper deposits may induce oxidative stress,
      modify expression of genes, directly inhibit proteins, and impair mitochondrial
      function, leading to hepatic, neuropsychiatric, renal, musculoskeletal, and other
      symptoms. Hepatocyte dysfunction initially manifests as steatosis and later may
      progress to other hepatic phenotypes such as acute liver failure, hepatitis, and
      fibrosis. In the brain, copper accumulates in astrocytes, leading to impairment
      of the blood-brain barrier and consequent damage to neurons and oligodendrocytes.
      Basal ganglia and brainstem are the brain regions with highest susceptibility to
      copper toxicity and their lesions lead to various combinations of movement and
      psychiatric disorders. This chapter will give an overview of the essential
      requirement of copper for biologic processes and the molecular mechanisms
      employed by cells to maintain their copper levels in a proper range. We will
      specify the physiologic functions of ATP7B and the consequences of its
      dysfunction and summarize the current knowledge on the pathogenesis of liver and
      neuropsychiatric disease. Finally, we will describe the consequences of copper
      overload in Wilson disease in other tissues.

PMID- 28433110
TI  - Animal models of Wilson disease.
AB  - Wilson disease (WD) is caused by ATPase copper-transporting beta (ATP7B)
      mutations and results in copper toxicity in liver and brain. Although the
      defective gene was identified in 1993, the specific mechanisms underlying copper
      toxicity and the remarkable phenotypic diversity of the disease are still poorly
      understood. Animal models harboring defects in the ATP7B homolog have helped to
      reveal new insights into pathomechanisms of WD. Four rodent models with ATP7B
      gene defects have been described - the Long-Evans Cinnamon (LEC) rat, inbred
      mouse models (toxic milk (tx), the Jackson Laboratory toxic milk (tx-j)), and the
      genetically engineered ATP7B-/- (knockout) mouse - all of which develop liver
      disease to different extents. Copper accumulation in parts of the brain
      accompanied by some neurologic involvement was revealed in LEC rats and tx/tx-j
      mice, but the pathology is less severe than human neurologic WD. Several dogs
      show hepatic copper toxicity resembling WD; however, brain involvement has not
      been observed and the underlying genetic defect is different. These models are of
      great value for examination of copper distribution and metabolism, gene
      expression, and investigation of liver and brain pathology. The availability of
      disease models is essential for therapeutic interventions such as drug, gene, and
      cell therapy. Findings made by animal studies may facilitate the development of
      specific therapies to ameliorate WD progression.

PMID- 28433111
TI  - Epidemiology and introduction to the clinical presentation of Wilson disease.
AB  - Our understanding of the epidemiology of Wilson disease has steadily grown since
      Sternlieb and Scheinberg's first prevalence estimate of 5 per million individuals
      in 1968. Increasingly sophisticated genetic techniques have led to revised
      genetic prevalence estimates of 142 per million. Various population isolates
      exist where the prevalence of Wilson disease is higher still, the highest being
      885 per million from within the mountainous region of Rucar in Romania. In
      Sardinia, where the prevalence of Wilson disease has been calculated at 370 per
      million births, six mutations account for around 85% of Wilson disease
      chromosomes identified. Significant variation in the patterns of presentation may
      however exist, even between individuals carrying the same mutations. At either
      extremes of presentation are an 8-month-old infant with abnormal liver function
      tests and individuals diagnosed in their eighth decade of life. Three main
      patterns of presentation have been recognized - hepatic, neurologic, and
      psychiatric - prompting their presentation to a diverse range of specialists.
      Deviations in the family history from the anticipated autosomal-recessive mode of
      inheritance, with apparent "pseudodominance" and mechanisms of inheritance that
      include uniparental isodisomy (the inheritance of both chromosomal copies from a
      single parent), may all further cloud the diagnosis. It can therefore take the
      efforts of an astute clinician with a high clinical index of suspicion to clinch
      the diagnosis of this eminently treatable condition.

PMID- 28433112
TI  - Wilson disease - liver pathology.
AB  - The liver in Wilson disease may demonstrate a wide range of damage patterns. Some
      patients may present almost no detectable microscopic pathology, while others
      display lesions consistent with fulminant hepatitis or acute liver failure. Most
      liver biopsy specimens show moderate to severe steatosis, variable degree of
      portal and/or lobular inflammation, and fibrosis eventually progressing to
      cirrhosis. Additional findings include liver cell degeneration and ballooning,
      Mallory hyaline bodies, liver cell necrosis, and glycogenation of periportal
      hepatocytic nuclei. None of the above lesions are specific for Wilson disease and
      should be interpreted in a wider medical context and particular clinical setting.
      The main message concerning liver pathology is that Wilson disease may be
      microscopically misinterpreted as many other liver diseases, including viral or
      autoimmune hepatitis, alcoholic/nonalcoholic steatohepatitis, toxic liver injury,
      cryptogenic cirrhosis, metabolic liver disease, and many others. The possibility
      of Wilson disease should be considered in all patients, especially young ones
      presenting unexplained liver diseases with many variable patterns of microscopic
      liver involvement.

PMID- 28433113
TI  - Wilson disease: brain pathology.
AB  - In Wilson disease (WD), brain cellular damage is thought to be due to copper
      deposition. Striatal lesions are the most characteristic lesions found in the
      brain of patients with neurologic symptoms, as emphasized in the initial reports
      of S.A.K. Wilson. WD brain lesions can be more diffuse, including in the pons,
      midbrain, thalamus, dentate nucleus, and, less frequently, corpus callosum and
      cortex. In rare cases, extensive cortical-subcortical lesions have been reported.
      Increased cellularity is noted in the lesions due to the proliferation of
      modified astrocytes named Alzheimer types of glia and specific cells, called
      Opalski cells, that are characteristic of WD. Although abnormalities in the
      putamen predominate in patients with dystonic syndrome, clinicopathologic
      correlations are scarce. Furthermore, the cerebral copper content is not
      correlated with the severity of the neuropathologic abnormalities or with the
      neuropsychiatric symptomatology. This fact raises the question of factors other
      than copper toxicity that may contribute to the pathogenesis of WD neurologic
      disturbances.

PMID- 28433114
TI  - Hepatic features of Wilson disease.
AB  - In Wilson disease (WD) defective AT7B function leads to biliary copper excretion
      and pathologic copper accumulation, particularly in liver and brain, where it
      induces cellular damage. Liver disease most often precedes neurologic or
      psychiatric manifestations. In most patients with neurologic or psychiatric
      symptoms there is some degree of liver disease at the time of disease
      presentation. Hepatic manifestations of WD can be extremely variable. Patients
      with clinically asymptomatic WD are often found by family screening or identified
      on routine laboratory testing. Others may have a clinical picture of chronic
      active hepatitis or of end-stage liver disease with cirrhosis. A minority present
      with acute liver failure, often on the background of advanced fibrosis.
      Complications from liver disease may be related to portal hypertension and
      concomitant liver disease may accelerate the course of liver disease. Liver
      cancer may occur in patients with WD, most commonly when cirrhosis and
      inflammation are present. The prognosis of patients with WD is excellent,
      especially for those without cirrhosis at the time of diagnosis, but requires
      timely initiation of appropriate therapy specific for WD and for the patient's
      liver disease independent of WD.

PMID- 28433115
TI  - Preface.

PMID- 28433116
TI  - Foreword.

PMID- 28433117
TI  - To Address Health Disparities for Latino Youth, Promote Their Engagement in
      Health Care.

PMID- 28433118
TI  - The Role of Public Health in Combatting Synthetic Cannabinoid Use in Adolescents.
AB  - As the country struggles to address an epidemic of alcohol and drug overdose, a
      wide-ranging category of chemical substances known as synthetic drugs have
      provoked a new sense of public urgency over the past decade. Synthetic
      cannabinoids, a heterogeneous and evolving set of synthetic compounds that act on
      endogenous cannabinoid receptors, have become particularly popular among
      adolescents due to their relative ease of access and reputation as a "legal
      high." The Baltimore City Health Department has worked to combat the recent surge
      in synthetic drug use through a major public awareness campaign, legislative
      reform, and retailer engagement and compliance initiative. In doing so, the city
      has built a coalition of clinicians, advocates, retailers, educators,
      legislators, and community members to fight synthetic cannabinoid use in
      Baltimore City. In this commentary piece, we offer strategies from our work and
      from that of our colleagues across the country for clinicians and communities
      fighting to stem the tide of recreational synthetic cannabinoid use.

PMID- 28433119
TI  - Cognition and Chronic Disease.

PMID- 28433120
TI  - Additional Cost Because of Pneumonia in Nursing Home Residents: Results From the
      Incidence of Pneumonia and Related Consequences in Nursing Home Resident Study.
AB  - OBJECTIVES: Pneumonia is a frequent condition in older people. Our aim was to
      examine the total healthcare cost related to pneumonia in nursing home (NH)
      residents over a 1-year follow-up period. DESIGN: This was a prospective,
      longitudinal, observational, and multicenter study that was a part of the
      Incidence of Pneumonia and related Consequences in Nursing Home Resident study.
      SETTING: Thirteen NHs located in Languedoc Roussillon and Midi-Pyrenees regions
      in France were included. PARTICIPANTS: Resident in NH, older than 60 years and
      had a group iso-resource score ranging from 2 to 5. MEASUREMENTS: Pneumonia
      events were characterized according to the Observatoire du Risque Infectieux en
      Geriatrie criteria. Direct medical and nonmedical costs were assessed from the
      French health insurance perspective. Healthcare resources was retrospectively
      gathered from the French Social Health Insurance database and valued using the
      tariffs reimbursed by the French health insurance. Sociodemographic variables,
      clinical factors, vaccinations, cognition, depression, functional status, frailty
      index, as well as group iso-resource score were also recorded. RESULTS: Among the
      800 patients initially included in the Incidence of Pneumonia and Related
      Consequences in Nursing Home Resident study, 345 which were listed in the
      database of the French Social Health Insurance were included in this economic
      study. Among them, 64 (18%) experienced at least 1 episode of pneumonia during
      the 1-year follow-up period. Mean annual total additional cost for a patient who
      experienced at least 1 episode of pneumonia during the 1 year follow-up period is
      2813?. On average, total annual costs increased by 60% to 93% when a patient
      experienced at least 1 episode of pneumonia. CONCLUSIONS: NH-acquired pneumonia
      has a great impact on total cost of care for NH residents. Our results suggest
      the potential economic savings that could be achieved if pneumonia could be
      prevented in NHs.

PMID- 28433121
TI  - A New Complication Associated with the Use of Prophylactic Intracameral
      Antibiotics: Hemorrhagic Occlusive Retinal Vasculitis.

PMID- 28433123
TI  - Optical Coherence Tomography Angiography of a Central Retinal Artery Occlusion
      Before and After Anterior Chamber Paracentesis.

PMID- 28433122
TI  - Intracameral Antibiotics in the Shadow of Hemorrhagic Occlusive Retinal
      Vasculitis.

PMID- 28433125
TI  - Pediatric Choroidal Coloboma with Macular Hole at the Edge of the Coloboma.

PMID- 28433124
TI  - Subconjunctival Granulomas from Extrascleral Silicon Oil Leak.

PMID- 28433126
TI  - Neonatal Graves' Eye Disease.

PMID- 28433127
TI  - Orbital and Intraocular Lymphoma in Contralateral Eyes: A Case of Cutaneous
      Aggressive CD-8+ T-Cell Lymphoma.

PMID- 28433128
TI  - Unusual Presentation of Choroidal Tuberculoma.

PMID- 28433129
TI  - Swept-source Optical Coherence Tomography Angiography Imaging in a Case of Uveal
      Melanoma.

PMID- 28433131
TI  - Corrigendum.

PMID- 28433132
TI  - Corrigendum.

PMID- 28433130
TI  - Epimacular Membrane Detachment Following Intravitreal Bevacizumab for Retinal
      Vasoproliferative Tumor.

PMID- 28433133
TI  - Corrigendum.

PMID- 28433134
TI  - Re: Campbell et al.: Diagnostic discrepancies in retinopathy of prematurity
      classification (Ophthalmology. 2016;123:1795-1801).

PMID- 28433136
TI  - Re: Popvic et al.: Efficacy and safety of femtosecond laser-assisted cataract
      surgery compared with manual cataract surgery: a meta-anaylsis of 14 567 eyes
      (Ophthalmology. 2016;123:2113-2126).

PMID- 28433135
TI  - Reply.

PMID- 28433137
TI  - Reply.

PMID- 28433138
TI  - Re: Pasquale et al.: Prospective study of oral health and risk of primary open
      angle glaucoma in men: data from the health professionals follow-up study
      (Ophthalmology. 2016;123:2318-2327).

PMID- 28433139
TI  - Reply.

PMID- 28433140
TI  - Reply.

PMID- 28433141
TI  - Re: Yarmohammadi et al.: Relationship between optical coherence tomography
      angiography vessel density and severity of visual field loss in glaucoma
      (Ophthalmology. 2016;123:2498-2508).

PMID- 28433142
TI  - Enhanced degradation of chitosan by applying plasma treatment in combination with
      oxidizing agents for potential use as an anticancer agent.
AB  - Solution plasma (SP) treatment in combination with oxidizing agents, i.e.,
      hydrogen peroxide (H2O2), potassium persulfate (K2S2O8) and sodium nitrite
      (NaNO2) were adopted to chitosan degradation in order to achieve fast degradation
      rate, low chemicals used and high yield of low-molecular-weight chitosan and
      chitooligosaccharide (COS). Among the studied oxidizing agents, H2O2 was found to
      be the best choice in terms of appreciable molecular weight reduction without
      major change in chemical structure of the degraded products of chitosan. By the
      combination with SP treatment, dilute solution of H2O2 (4-60mM) was required for
      effective degradation of chitosan. The combination of SP treatment and dilute
      solution of H2O2 (60mM) resulted in the great reduction of molecular weight of
      chitosan and water-soluble chitosan was obtained as a major product. The
      resulting water-soluble chitosan was precipitated to obtain COS. An inhibitory
      effect against cervical cancer cell line (HeLa cells) of COS was also examined.

PMID- 28433143
TI  - Transcrystallization of polypropylene in the presence of polyester/cellulose
      nanocrystal composite fibers.
AB  - Pristine cellulose nanocrystal (CNC) and acetylated one (aCNC) were used as the
      modifier to change the surface properties of poly(trimethylene terephthalate)
      (PTT) fibers for the transcrystallization study of polypropylene (PP). The
      results reveal that all three kinds of fibers, including the neat PTT, PTT/CNC
      and PTT/aCNC ones can induce PP transcrystallization. But the PTT/aCNC fiber
      filled PP system shows the most remarkable transcrystallization behavior because
      of the highest nucleation density of PTT/aCNC fiber. The long period and lamellar
      thickness of two composite fiber-filled PP systems increase as compared with the
      neat PTT fiber-filled one, which is caused by the reduced system undercooling and
      higher surface energy level of composite fibers. Accordingly, the former two
      systems show the lower transcrystal growth rates than the latter, which is
      further analyzed by the secondary nucleation theory. This work can provide useful
      information on the control of PP transcrystallization using the CNC-filled
      polyester composite fibers.

PMID- 28433144
TI  - Purification, characterization, and bioactivities of a polysaccharide from
      mycelial fermentation of Bjerkandera fumosa.
AB  - In this work, a novel polysaccharide (named DBFM3) was isolated from mycelia of
      Bjerkandera fumosa by DEAE-32 and Sepharose CL-6B column chromatography. High
      performance gel permeation chromatography showed that DBFM3 was homogeneous, with
      an average molecular weight of 1.8*105Da. Structural characteristics of the
      purified fraction were investigated by high-performance liquid chromatography
      (HPLC), FT-IR, and NMR. HPLC analysis indicated that DBFM3 was composed of
      mannose, galacturonic acid, and galactose at molar ratios of 1:18.16:0.702.
      Spectral analysis suggested that DBFM3 had (1->6), (1->3,6), (1->3) linkages and
      pyranose conformation. Antioxidant assay in vitro showed that DBFM3 exhibited 1,1
      diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical scavenging activity, and
      has protective effect against DNA damage and damage to SH-SY5Y cells induced by
      H2O2. Immunological tests indicated that DBFM3 significantly increased lymphocyte
      proliferation in vitro. Furthermore, DBFM3 increased the proliferation of
      lymphocytes in the presence of concanavalin A or lipopolysaccharide as mitogen.

PMID- 28433145
TI  - Influence of the radial stem composition on the thermal behaviour of miscanthus
      and sorghum genotypes.
AB  - The hypothesis made is that thermal resistance of sorghum and miscanthus stem
      pieces taken at well-defined positions of the stem is simply related to their
      biochemical composition. For miscanthus, two different genotypes and two
      internode levels were selected. For each region, the stem was divided into three
      radial layers. For sorghum, two different genotypes were selected and the stem
      was divided into the same three radial layers. The results show that the thermal
      analysis is only sensitive to very large variations of compositions. But aside of
      such large composition differences, it is impossible to correlate thermal effects
      to biochemical composition even on very small size, well-identified pieces of
      plant materials. The interplay between sugar-based components, lignin and
      minerals is totally blurring the thermal response. Extreme care must be exercised
      when willing to explain why a given plant material has a thermal behaviour
      different of another plant material.

PMID- 28433147
TI  - Mucopolysaccharide from cuttlefish: Purification, chemical characterization and
      bioactive potential.
AB  - The sulfated mucopolysaccharide (GAG) was isolated from S. pharonis and the
      carbohydrate and protein content was found to be 62.4% and 3.9%. The disaccharide
      profile of sulfated GAG composed glucuronic acid, N-acetyl glucosamine and
      sulfate content by contributing 50.11%, 38.00% and 27.69% respectively. The
      carbon, hydrogen and nitrogen content of the sulfated GAG showed 14.80%, 1.68%
      and 2.99% respectively. The molecular weight of sulfated GAG was calculated as
      27kDa and the structural characterization was done by Fourier Transform Infrared
      (FT-IR) and NMR Spectroscopy. The Activated Partial Thromboplastin Time (APTT)
      and Prothrombin Time (PT) of sulfated GAG were determined as 91 IU and 39.55 IU
      at 25MUg/ml respectively. Further the sulfated GAG reported the cytotoxic effect
      (CC50) of 1100MUg/ml concentration on Vero cell line. The sulfated GAG reported
      the anticancer activity against HeLa cell line with an inhibition rate of 18.65%
      66.13% at 50-250MUg/ml concentration. The sulfated GAG can be considered as a
      potent anticoagulant and anticancer drug in future.

PMID- 28433146
TI  - Chemo-bacterial synthesis of conjugatable glycosaminoglycans.
AB  - Conjugatable glycosaminoglycans hold promise for medical applications involving
      the vectorization of specific molecules. Here, we set out to produce bacterial
      chondroitin and heparosan from a conjugatable precursor using metabolically
      engineered Escherichia coli strains. The major barrier to this procedure was the
      glucuronylation of a lactosyl acceptor required for polymerization. To overcome
      this barrier, we designed E. coli strains expressing mouse beta-1,3-glucuronyl
      transferase and E. coli K4 chondroitin and K5 heparosan synthases. These
      engineered strains were cultivated at high density in presence of a lactose-furyl
      precursor. Enzymatic polymerization occurred on the lactosyl precursor resulting
      in small chains ranging from 15 to 30kDa that accumulated in the cytoplasm. Furyl
      terminated polysaccharides were produced at a gram-per-liter scale, a yield
      similar to that reported for conventional strains. Their efficient conjugation
      using a Diels-Alder cycloaddition reaction in aqueous and catalyst-free
      conditions was also confirmed using N-methylmaleimide as model dienophile.

PMID- 28433148
TI  - Mechanics and transport phenomena in agarose-based hydrogels studied by
      compression-relaxation tests.
AB  - Hydrogels are widespread materials, used in several frontier fields, due to their
      peculiar behavior: they couple solvent mass transport to system mechanics,
      exhibiting viscoelastic and poroelastic characteristics. The full understanding
      of this behavior is crucial to correctly design such complex systems. In this
      study agarose gels has been investigated through experimental stress-relaxation
      tests and with the aid of a 3D poroviscoelastic model. At the investigated
      experimental conditions, the agarose gels samples show a prevalent viscoelastic
      behavior, revealing limited water transport and an increase of the stiffness as
      well as of the relaxation time along with the polymer concentration. The model
      parameters, derived from the fitting of some experimental data, have been
      generalized and used to purely predict the behavior of another set of gels. The
      stress-relaxation tests coupled with mathematical modeling demonstrated to be a
      powerful tool to study hydrogels' behavior.

PMID- 28433149
TI  - Fabrication and evaluation of thermosensitive chitosan/collagen/alpha, beta
      glycerophosphate hydrogels for tissue regeneration.
AB  - Thermosensitive hydrogels whose physiological properties are similar to
      extracellular matrix have been extensively used for tissue regeneration.
      Polysaccharides and proteins, as biocompatible substrates similar to bio
      macromolecules that could be recognized by human body, are two preferred polymers
      for fabrication of such hydrogels. A series of novel thermosensitive hydrogels
      (CS-ASC-HGs) containing chitosan (CS) and acid-soluble collagen (ASC) were thus
      prepared, in the presence of alpha, beta-glycerophosphate, to mimic extracellular
      microenvironment for tissue regeneration. Rheological measurements demonstrated
      excellent thermosensitivity. FT-IR and SEM indicated CS-ASC-HGs possessed 3D
      porous architectures with fibrous ASC, and the molecular structure of ASC was
      well-maintained in hydrogels. Hemolysis, acute toxicity, and cytotoxicity tests
      suggested CS-ASC-HGs were of good biocompatibility. CS-ASC-HGs were able to
      support the survival and proliferation of L929 cells encapsulated in them.
      Moreover, CS-ASC-HGs had better pH stability and biocompatibility than pure CS
      hydrogel. These results suggested that CS-ASC-HGs could serve as promising
      scaffolds for tissue regeneration.

PMID- 28433150
TI  - Production of prebiotic-xylooligosaccharides from alkali pretreated mahogany and
      mango wood sawdust by using purified xylanase of Clostridium strain BOH3.
AB  - Xylooligosaccharides (XOS) are emerging prebiotics which can be produced from
      lignocellulosic biomass including agro-residues and hardwood. In this study, we
      report the production of XOS from thermal-alkali pretreated hardwood such as
      mahogany and mango by using a purified xylanase from Clostridium strain BOH3. In
      the first approach, pure xylan is extracted from mahogany and mango hardwood and
      then the pure xylan is hydrolyzed by using the xylanase. In this case, 572 and
      504mg XOS/g pure xylan were obtained from mahogany and mango woods, respectively.
      In the second approach, the same xylanase is employed to hydrolyze sawdust of
      hardwood after different types of pretreatments. After a thermal (121 degrees C
      for 15min) pretreatment under a mild alkaline (0.05N NaOH) condition, the
      pretreated mahogany and mango sawdust can be utilized directly to produce 89.5
      and 67.6mg XOS/g pretreated sawdust, respectively. XOS produced from the
      pretreated sawdust show strong prebiotic effects on Bifidobacteria and
      Lactobacilli. This report shows the possibility of producing XOS from pretreated
      woody wastes without using pure xylan as a substrate.

PMID- 28433151
TI  - Integrated production of lignin containing cellulose nanocrystals (LCNC) and
      nanofibrils (LCNF) using an easily recyclable di-carboxylic acid.
AB  - Here we demonstrate di-carboxylic acid hydrolysis for the integrated production
      of lignin containing cellulose nanocrystals (LCNC) and nanofibrils (LCNF) using
      two unbleached mixed hardwood chemical pulps of lignin contents of 3.9 and 17.2%.
      Acid hydrolysis experiments used maleic acid solution of 60wt% concentration at
      120 degrees C for 120min under ambient pressure. Yields of LCNC were low of less
      than 6% under this set of conditions. The higher lignin content sample produced
      LCNC with greater height (diameter) of 25nm but similar length of approximately
      230nm to that from the lower lignin content fibers (height of 20nm).
      Interestingly, the higher lignin content sample resulted in LCNF with smaller
      height (diameter) of 7nm but longer length of >1MUm, or greater aspect ratio than
      the LCNF from the lower lignin fibers of height 10nm and length <1MUm. Lignin
      protected cellulose from esterification which resulted in LCNC and LCNF that was
      less carboxylated compared to those lignin-free CNC and CNF and therefore had
      lower charges. However, lignin is more hydrophobic and thermally stable than
      carbohydrates therefore LCNC and LCNF are favorable for composite applications.

PMID- 28433152
TI  - Biodegradable blends of urea plasticized thermoplastic starch (UTPS) and
      poly(epsilon-caprolactone) (PCL): Morphological, rheological, thermal and
      mechanical properties.
AB  - Biodegradable blends of urea plasticized thermoplastic starch (UTPS) and
      poly(epsilon-caprolactone) (PCL) were prepared in a co-rotating twin screw
      extruder. The UTPS and PCL content varied in a range of 25wt%. The materials were
      characterized by capillary rheometry, scanning electron microscopy (SEM),
      termogravimetry (TGA), differential scanning calorimetry (DSC) and tensile tests.
      Capillary rheometry showed better interaction between UTPS and PCL at 110 degrees
      C than at 130 degrees C. SEM showed immiscibility of all blends and good
      dispersion of UTPS in PCL matrix up to 50wt%. However, a co-continuous morphology
      was found for UTPS/PCL 75/25. Thermal analysis showed that introducing PCL in
      UTPS, increased Tonset due to higher thermal stability of PCL, and blends
      presented an intermediate behavior of neat polymers. The presence of PCL in
      blends improved significantly the mechanical properties of neat UTPS. Because
      they are totally biodegradable, these blends can be vehicles for controlled or
      slow release of nutrients to the soil while degraded.

PMID- 28433153
TI  - Polyethylenimine/kappa carrageenan: Micro-arc oxidation coating for passivation
      of magnesium alloy.
AB  - The aim of this study was to combine micro-arc oxidation (MAO) and self-assembly
      technique to improve corrosion resistivity of AZ91 alloy. While a silicate
      fluoride electrolyte was adopted for MAO treatment, polyethylenimine (PEI)/kappa
      carrageenan (KC) self-assembly coating was applied as the second coating layer.
      Resulted demonstrated the formation of forsterite-fluoride containing MAO coating
      on AZ91 alloy depending on the voltage and time of anodizing process. Addition of
      the second PEI/KC coating layer on MAO treated sample effectively enhanced the
      adhesive strength of MAO coated sample due to filling the pores with polymers and
      increase in the mechanical interlocking of coating to the substrate. Moreover,
      the corrosion evaluation considered by potentiodynamic polarization and
      electrochemical impedance spectroscopy confirmed that double layered PEI/KC:MAO
      coating presented superior resistance to corrosion attack. It is envisioned that
      the proposed double layered PEI/KC:MAO coating could be useful for biomedical
      applications.

PMID- 28433154
TI  - Non-immunogenic, porous and antibacterial chitosan and Antheraea mylitta silk
      sericin hydrogels as potential dermal substitute.
AB  - Limitation of existing grafts including restricted donor site, risks of immune
      reactions, infectious diseases and high cost alarms the growing need of natural,
      cost effective and functional graft as the dermal substitute. We fabricate stable
      (>6 weeks) and porous (57.23-75.22MUm) yet flexible (in variable pH) matrices
      using Antheraea mylitta sericin crosslinked with well known biocompatible
      polysaccharide chitosan by natural crosslinker (genipin) without using any harsh
      chemical. The fabricated matrices are characterized in terms of chemical
      modifications (Fourier transform infrared spectroscopy), crystallinity (X-ray
      diffraction), swelling, degradability and thermal stability. The hydrogels show
      good adhesion, migration, proliferation and viability of human dermal
      fibroblasts. The matrices cause no significant immune response of inflammatory
      cytokines (TNF-alpha and IL-1beta) and hemolysis of human blood. These also
      retain their intrinsic antioxidant (196.1+/-17.7MUM Fe (II)/mg) and antibacterial
      (8-15mm zone of inhibition) properties. These results indicate their potential as
      a cost effective and antibacterial dermal substitute.

PMID- 28433156
TI  - Ternary natural deep eutectic solvent (NADES) infused phthaloyl starch as cost
      efficient quasi-solid gel polymer electrolyte.
AB  - A first-of-its-kind, eco-friendly quasi-solid bioelectrolyte derived from potato
      starch was prepared. Starch was chemically modified via phthaloylation to
      synthesize amorphous, hydrophobic starch derivative and the attachment of the
      phthaloyl group was confirmed via FTIR which showed phthalate ester peak at
      1715cm-1; and 1H NMR peaks between 7.30-7.90ppm attributed to the aromatic
      protons of the phthaloyl group. The resulting starch derivative was then infused
      with ternary natural deep eutectic solvent (NADES) made from different molar
      ratios of choline chloride, urea and glycerol. Electrochemical Impedance
      Spectroscopy (EIS) revealed that the highest ionic conductivity was obtained by
      the system consisting of NADES with choline chloride:urea:glycerol in molar
      ratios of 4:6:2, with a magnitude of 2.86mScm-1, hence validating the prospects
      of the materials to be further experimented as an alternative electrolyte in
      various electrochemical devices.

PMID- 28433155
TI  - A highly regular fucosylated chondroitin sulfate from the sea cucumber Massinium
      magnum: Structure and effects on coagulation.
AB  - A fucosylated chondroitin sulfate MM was isolated from the sea cucumber Massinium
      magnum. Structure of this polysaccharide was determined using chemical and NMR
      spectroscopic methods. The backbone of MM was shown to consist mainly of
      chondroitin sulfate E units with a small portion (about 10%) of chondroitin
      sulfate A fragments. Practically one type of branches Fuc3S4S attached to O-3 of
      GlcA residues was found in the polysaccharide molecules. The main repeating units
      of MM are ->4)-[alpha-l-Fuc3S4S-(1->3)]-beta-d-GlcA-(1->3)-beta-d-GalNAc4S6S-(1
      >, whereas the minor repeating units are ->4)-[alpha-l-Fuc3S4S-(1->3)]-beta-d
      GlcA-(1->3)-beta-d-GalNAc4S-(1->. Anticoagulant activity of MM determined in APTT
      and TT tests was shown to be lower than that of heparin, but higher than that of
      enoxaparin. In the experiments with purified proteins MM effectively potentiated
      inhibition of thrombin and factor Xa by ATIII. Besides, MM did not induce
      platelets aggregation in platelets rich plasma.

PMID- 28433157
TI  - Enhanced mechanical properties of chitosan/nanodiamond composites by improving
      interphase using thermal oxidation of nanodiamond.
AB  - Polymer composite films based on chitosan (CS) and nanodimaond (ND) were prepared
      using solution casting method. ND with variable contents of carboxylic functional
      group was prepared using thermal oxidation at temperature of 420 degrees C under
      air atmosphere at various durations of 1.5 and 4.5h. The interfacial interaction
      between NDs and CS and morphological evolution of CS in presence of NDs were
      investigated by Fourier transform infrared (FTIR), differential scanning
      calorimeter (DSC) and X-ray diffraction (XRD) analyses. A significant improvement
      in tensile strength (~85%) and tensile modulus (~125%) of CS was achieved by
      oxidized ND (OND) obtained at higher oxidation time of 4.5 at low concentrations
      (below 1.5wt%). Theoretical analyses based on micromechanical models showed that
      the ND with higher degree of carboxylic functionality provided thicker and
      stronger interphase region which was reflected in higher mechanical properties.
      The equilibrium water uptake of CS decreased by incorporating ND and increasing
      its degree of carboxyl functionality.

PMID- 28433158
TI  - Characterization of a sulfated galactoglucan from Antrodia cinnamomea and its
      anticancer mechanism via TGFbeta/FAK/Slug axis suppression.
AB  - A sulfated 1,4-beta-d-galactoglucan (B86-III) with 1,6-branches was isolated and
      identified from Antrodia cinnamomea. The repeating unit of B86-III was proposed
      based on one-dimensional 1D (1H, 13C and DEPT-135) and 2D (DQF-COSY, TOCSY, HSQC
      and HMBC) NMR spectra. The conformation of the sugars was hypothesized to be a
      rare boat form instead of a 4C1 chair form. The sulfate substitutions were
      suggested to be on the C-2 and C-3 positions, resulting in the following
      structure: B86-III inhibited the viability of H1975 lung cancer cells via cell
      apoptosis, including the activation of caspase 3 and PARP. Transforming growth
      factor beta receptor (TGFR) and its downstream signaling FAK and Slug are
      involved in lung tumorigenesis. B86-III downregulated TGFR I protein levels and
      inhibited FAK phosphorylation, resulting in inhibition of Slug expression and
      migration. This study is the first to characterize sulfated polysaccharides with
      a rare boat-form conformation and identify the mechanism of inhibition lung
      cancer cell.

PMID- 28433159
TI  - Glucuronoarabinoxylans as major cell walls polymers from young shoots of the
      woody bamboo Phyllostachys aurea.
AB  - Young shoots of Phyllostachys aurea showed glucuronoarabinoxylans (GAX) as the
      major hemicellulosic components, being extracted in major amounts with 1M KOH
      (ratio Xyl:Ara:GlcA, 100:67:8), but also with water, showing a broad structural
      variability. Mixed linkage glucans were also present, but in minor amounts,
      mostly concentrated in the 4M KOH extracts, while pectin polymers were very
      scarce. Arabinogalactan proteins were an important part of water extracts,
      determined by the presence of the typical arabinogalactan structures (3- and 6
      linked Gal p; terminal and 5-linked Ara f), in addition to small amounts of
      hydroxyproline (2-3% of total protein) and positive reaction to Yariv's reagent.
      Morphological and anatomical characteristics of young shoots are described, as
      well as localization of some cell wall components, and related with chemical
      analysis. A method for determination of uronic acids as their N-propylaldonamide
      acetates and separation and quantification by GC/MS was adapted for its use with
      grass cell wall fractions.

PMID- 28433161
TI  - Does kappa-carrageenan thermoreversible gelation affect beta-carotene oxidative
      degradation and bioaccessibility in o/w emulsions?
AB  - In the present work oil-in-gel (o/g) emulsions comprising 0.4-1% w/w kappa
      carrageenan in the absence and presence of Ca2+ (20mM) were investigated for
      their ability to hamper the oxidative degradation under isothermal (5, 20 and 37
      degrees C) ambient air storage conditions and promote the in vitro
      bioaccessibility of beta-carotene. The mechanical and structure conformational
      aspects of the o/g emulsions throughout in vitro digestion were measured by means
      of oscillatory rheology and optical microscopy. Although the addition of kappa
      carrageenan reduced by more than 50% (from 0.85 to 0.40day-1) the beta-carotene
      oxidative degradation rates, only minor differences were detected in terms of
      gelation method (ca. 0.42 and 0.39day-1 for ionotropic and coldset systems) and
      biopolymer concentration (0.38-0.42day-1). The bioaccessibility of beta-carotene
      was significantly higher in coldset o/g emulsions (ca. 43%) compared to the
      ionically mediated ones (ca. 36%). With the exception of 0.4% kappa-carrageenan
      containing o/g emulsions (55.4 and 49.7% for control and 0.4% kappa-carrageenan
      respectively), the beta-carotene bioaccessibility was significantly reduced with
      the increase in kappa-carrageenan concentration (ranging from 34 to 38.9%).

PMID- 28433160
TI  - Thiolated chitosan micelles: Highly mucoadhesive drug carriers.
AB  - Current study was aimed to generate thiolated chitosan micelles based on
      amphiphilic chitosan-stearic acid conjugate (CSA) and to evaluate adhesive
      properties on mucosal membranes. Chitosan-stearic acid-thioglycolic acid (CSA
      TGA) conjugate was synthesized via stearic acid linkage to chitosan and later,
      thioglycolic acid was covalently attached to CSA. CSA-TGA and CSA were
      characterized by degree of amine substitution, thiol group determination, ATR
      FTIR and cytotoxicity analysis. Micelle size was 13.40+/-9.38 and 26.30+/-26.86nm
      and zeta potential -0.01 and 0.03mV for CSA and CSA-TGA, respectively. In porcine
      mucus CSA-TGA micelles exhibited 1.80-, 2.12- and 1.72-fold increase in dynamic
      viscosity, elastic modulus and viscous modulus, respectively. Compared to CSA
      micelles CSA-TGA micelles remained up to 56.1- fold and 28.6- fold higher degree
      attached on intestinal and vaginal mucosa, respectively. Taking possibility to
      incorporate both lipophilic and hydrophilic drugs into these micelles into
      account, thiol functionalized micelles could be promising carriers for mucosal
      drug delivery.

PMID- 28433162
TI  - Tocopheryl acetate release from microcapsules of waxy maize starch.
AB  - Diffusion coefficients are utilised to provide a realistic approach in the
      quantification of mass transport phenomena, which are important for the delivery
      of bioactivity from high-solid biopolymer systems. Following this mechanistic
      consideration, we employ spray drying to produce microcapsules of waxy maize
      starch that suspend homogeneously tocopheryl acetate. An array of physicochemical
      techniques including dynamic oscillation in-shear or compression mode, microDSC,
      WAXD, FTIR, scanning electron or optical microscopy, and UV-vis assays were
      utilised to relate structural properties of the macromolecular network to
      diffusivity of the bioactive compound. A modified version of the free-volume
      theory designed to address molecular diffusion was evaluated over a wide
      temperature range. Predictive capabilities were facilitated by proposing a
      mathematical relationship between diffusion coefficient of tocopheryl acetate and
      fractional free volume of waxy maize starch. Moreover, the theoretical approach
      is able to accurately describe the extent of cooperativity in the vitamin
      biopolymer interaction that determines transport kinetics.

PMID- 28433163
TI  - Fabrication of schizophyllan hydrogel via orthogonal thiol-ene
      photopolymerization.
AB  - Schizophyllan (SPG) is a water soluble beta-glucan, which is obtained from
      Schizophyllum commune. SPG has been widely explored with its unique properties
      such as triple helical structure, immune-modulation, and anti-tumoral activity.
      In this study, we tried to fabricate SPG hydrogel via thiol-ene
      photopolymerization. SPG-norbornene and SPG-thiol were synthesized from
      ultrasonicated SPG. Two types of SPG hydrogels (SPG and PEG/SPG hybrid) were
      formed via thiol-ene photo-click reaction. By controlling the SPG content and
      stoichiometric balance of norbornene and thiol groups, swelling ratio and shear
      elastic modulus of SPG hydrogel could be controlled in the range of 20-60 and 0.5
      10kPa, respectively. For PEG/SPG hybrid hydrogel, we found that the triple
      helical structure of SPG played a role in physical network formation with thiol
      ene cross-linking. The degradability of SPG hydrogel could be also modulated by
      varying formulation. Therefore, such highly tunable SPG hydrogels would be
      utilized for various applications.

PMID- 28433164
TI  - Characterization and application of cellulose acetate synthesized from sugarcane
      bagasse.
AB  - The synthesis and application of cellulose acetate (CA) from sugarcane bagasse
      were investigated. Firstly, cellulose was extracted by a sequential treatment
      with H2SO4 (10% v/v), NaOH (5% w/v), EDTA (0.5% w/V), and H2O2 (5% v/v), and
      characterized by X-ray diffraction (DRX). After the acetylation of the extracted
      cellulose, CA was characterized using Fourier transform infrared spectroscopy
      (FTIR), differential scanning calorimetry (DSC), and thermogravimetry analysis
      (TGA), and was applied in the membrane production. The membranes were analyzed by
      DSC and atomic force microscopy (AFM), and tested in the flux of water vapor to
      determinate the best conditions for membrane manufacturing. FTIR analysis proved
      the replacement of free OH groups by acetyl groups, and the thermal analysis
      showed that sugarcane bagasse CA possessed thermal properties compared to
      commercial grade CA. The best conditions to prepare membrane were: 3% (w/v) of
      polymer/solvent relation, 10min of solvent evaporation time, and 20 degrees C as
      temperature for the coagulation bath. These results show that CA can be
      successfully synthesized from sugarcane bagasse and applied in membrane
      preparation.

PMID- 28433165
TI  - Efficiency of xylanases from families 10 and 11 in production of xylo
      oligosaccharides from wheat arabinoxylans.
AB  - This study investigated the effect of xylanases from families 10 and 11 on the
      production of small chain arabinoxylo-oligosaccharides (AXOS) (X2-X4) from wheat
      arabinoxylans, and identified the impact that pH, temperature and time exposed to
      xylanase have on this process. Xylanase from family 10 had greater hydrolytic
      efficiency and resulted in heightened AXOS production compared with xylanase from
      family 11 or family 10 and 11 combined. The pH of the environment had a
      significant effect on AXOS production (P<0.001) and the greatest conversion of
      arabinoxylans into AXOS was observed at pH 2.5. The effects of temperature of the
      environment and amount of time the samples were exposed to the xylanase on AXOS
      production were inconsistent and were dictated by pH and xylanase family, as
      evidenced by interactions between temperature and pH (P=0.016) and xylanase
      family (P=0.032) and time and pH (P=0.007).

PMID- 28433166
TI  - Chitosan-graphene oxide films and CO2-dried porous aerogel microspheres:
      Interfacial interplay and stability.
AB  - The intimate interplay of chitosan (CS) and graphene oxide (GO) in aqueous acidic
      solution has been explored to design upon casting, nanostructured "brick-and
      mortar" films (CS-GO-f) and by acidic-to-basic pH inversion, porous CO2-dried
      aerogel microspheres (CS-GO-m). Owing to the presence of oxygenated functional
      groups in GO, good-quality crack-free hybrid films were obtained. Mechanical
      properties were improved independently of the GO content and it was found that a
      20wt% loading affords hybrid film characterized with a Young modulus three times
      superior to that reached with the same loading of layered clay. The presence of
      graphene oxide was found to be detrimental for the thermal stability of the
      polysaccharide at T <350 degrees C, a fact attributed to the well-established
      decomposition of the oxygenated functional groups of the graphene sheets.
      Irrespective to the graphene oxide loading, chitosan-graphene oxide mixture
      preserves the gelation memory of the polysaccharide. Supercritical drying of the
      resulting soft hydrogels provides macroporous network with surface areas ranging
      from 226m2g-1 to 554m2g-1. XPS and RAMAN analyses evidenced the selective
      reduction of GO sheets inside of these microspheres, affording the hitherto
      unknown macroporous chitosan-entangled-reduced graphene oxide (CS-rGO-m)
      aerogels. Improvement in both hydrothermal stability (under water reflux) and
      chemical stability (under acidic conditions) have been noticed for chitosan
      graphene oxide microspheres with respect to non-modified chitosan and chitosan
      clay bio-hybrids, a result rooted in the substantial hydrophobic character
      imparted by the addition of graphenic material to the polysaccharide skeleton. In
      essence, this contribution demonstrates that graphene oxide loading do not
      disturb neither the filmogenicity of chitosan nor its gelation ability and
      constitutes a promising route for novel chitosan-based functional hybrid
      materials.

PMID- 28433167
TI  - Ammonium-pillared montmorillonite-CoFe2O4 composite caged in calcium alginate
      beads for the removal of Cs+ from wastewater.
AB  - Novel and magnetic adsorbent ammonium-pillared montmorillonite-CoFe2O4 composite
      caged in calcium alginate beads was prepared by using non-toxic raw materials.
      The morphology, magnetic properties, functional groups, and crystal structure of
      the compound were characterized by SEM, VSM, FT-IR and XRD. The adsorption
      behaviors were also investigated via adsorption experiments and response surface
      methodology was used to optimize the operation conditions. The beads showed high
      selectivity for Cs+ in the presence of Na+ and could be rapidly separated from
      the mixed solution under an external magnetic field. The maximum adsorption
      capacity was 86.46mg/g, which is higher than that of previously reported magnetic
      adsorbents. The adsorption kinetics and adsorption isotherms could be expressed
      by the pseudo-second-order and Langmuir isotherm, respectively. The relationship
      between a dependent variable (i.e., removal efficiency or adsorption capacity)
      and an independent variable (i.e., initial concentration, contact time, and
      adsorbent dosage) could be fitted to a quadratic second-order polynomial
      equation. The adsorption mechanism primarily involved ion exchange while
      coordination reactions also contributed.

PMID- 28433168
TI  - Evaluation of the physical properties and conservation of the antioxidants
      content, employing inulin and maltodextrin in the spray drying of blueberry
      juice.
AB  - In this work, two carbohydrate polymers, inulin (I) and maltodextrin (MX), were
      compared as carrying agents in the spray drying of blueberry juice (BJ). The
      physicochemical properties and the conservation of the antioxidants content were
      characterized. Both systems, showed non-agglomerated particles and light-purple
      color appearance. Powders were subjected to the adsorption of water, and the
      glass transition temperature (Tg) decreased with the water activity. The
      evolution of the microstructure in the MX-BJ remained unchanged, while the I-BJ
      presented an abrupt change from amorphous to crystalline. This was corroborated
      by scanning electron microscopy (SEM), observing in the I-BJ system, the change
      from spherical into irregular shape particles. In the conservation of the
      antioxidants content, the MX-BJ showed a better performance. Anyhow, the
      performance of both carbohydrate polymers as carrying agents in the spray drying
      of BJ was effective.

PMID- 28433169
TI  - Effectiveness of N,O-carboxymethyl chitosan on destabilization of Marine Diesel,
      Diesel and Marine-2T oil for oil spill treatment.
AB  - Oil spills are the significant sources of hydrocarbons entering in the receiving
      aquatic environment. An efficient method to remove hydrocarbons from water
      resources is adsorption. In this study, water soluble N,O-carboxymethyl chitosan
      (NO-CS) was synthesized by carboxymethylation of chitosan in a hydro-alcoholic
      medium at 50 degrees C by chloroacetic acid. The polymer was characterized
      through degree of deacetylation, degree of substitution, FTIR and 1H NMR.
      Effectiveness of NO-CS as an adsorbent was studied as a function of dosage,
      salinity and pH to destabilize the Marine diesel (Oil-1), Diesel (Oil-2) and
      Marine-2T oil (Oil-3) into small oil droplets of less than 100MUm. Optical
      microscope was used for studying the size of oil droplets and adsorption effect
      of the oils on this polymer. The destabilization of marine diesel was the most
      effective among the studied three oils, which showed excellent adsorption at sea
      water alkalinity and salinity.

PMID- 28433170
TI  - Structural characterization and immuno-enhancing activity of a highly branched
      water-soluble beta-glucan from the spores of Ganoderma lucidum.
AB  - A water soluble beta-glucan (GLSWA-I) with a weight average molecular weight
      ~1.57*105g/mol, isolated from the aqueous extract of the broken cellular wall
      Ganoderma lucidum spores, was purified by anion-exchange and gel-permeation
      chromatography. The immunological activity test in vivo showed that GLSWA-I could
      significantly promote dinitrochlorobenzene (DNCB) induced delayed-type ear
      swelling in mice. Based on the monosaccharides composition analysis, methylation
      analysis, IR, 1D and 2D NMR spectroscopy, the repeating unit of polysaccharide
      GLSWA-I was elucidated as follows.

PMID- 28433171
TI  - Gellan gum based physical hydrogels incorporating highly valuable endogen
      molecules and associating BMP-2 as bone formation platforms.
AB  - Physical hydrogels have been designed for a double purpose: as growth factor
      delivery systems and as scaffolds to support cell colonization and formation of
      new bone. Specifically, the polysaccharide gellan gum and the ubiquitous
      endogenous molecules chondroitin, albumin and spermidine have been used as
      exclusive components of these hydrogels. The mild ionotropic gelation technique
      was used to preserve the bioactivity of the selected growth factor, rhBMP-2. In
      vitro tests demonstrated the effective delivery of rhBMP-2 in its bioactive form.
      In vivo experiments performed in the muscle tissue of Wistar rats provided a
      proof of concept of the ability of the developed platforms to elicit new bone
      formation. Furthermore, this biological effect was better than that of a
      commercial formulation currently used for regenerative purposes, confirming the
      potential of these hydrogels as new and innovative growth factor delivery
      platforms and scaffolds for regenerative medicine applications.

PMID- 28433172
TI  - Preparation and characterization of chitosan derivatives and their application as
      flame retardants in thermoplastic polyurethane.
AB  - Our previous work has demonstrated that chitosan (CS) can be directly used as
      charring agents. In this paper, efforts were made to further improve the thermal
      stability and charring ability of CS by reacting with benzaldehyde,
      salicylaldehyde and hydroxybenzaldehyde respectively to obtain different CS
      derivatives. CS derivatives in association with ammonium polyphosphate (APP) was
      then introduced into thermoplastic polyurethane (TPU) to prepare flame retardant
      TPU composites. The sample containing 18.75% APP and 6.25% salicylaldehyde
      modified CS (SCS) achieved the maximal limiting oxygen index of 29.5%, passed the
      V-0 rating and significantly decreased the peak heat release rate from 840.8kW/m2
      of neat TPU to 206.2kW/m2. Thermogravimetric analysis and char morphology
      observation demonstrated that SCS/APP could promote the char formation to form
      more intact intumescent char structure. It was proposed that the synergism
      between CS derivatives and APP might be responsible for the improvement of flame
      retardancy.

PMID- 28433173
TI  - Dye adsorption and photo-induced recycling of hydroxypropyl cellulose/molybdenum
      disulfide composite hydrogels.
AB  - A novel environmental friendly dye adsorbent composited of hydroxypropyl
      cellulose (HPC) and molybdenum disulfide (MoS2) were fabricated, which can be
      recycled and reused by illumination due to the photo-catalytic properties of
      MoS2. In order to promote a more homogeneous dispersion of MoS2 nanosheets in
      HPC, MoS2 was functionalized with HPC chains through esterification. The
      successful functionalization of MoS2 was confirmed by FTIR, XRD, XPS
      characterizations. The morphologies of the HPC and HPC-MoS2/HPC hydrogels were
      compared by SEM. The obtained HPC-MoS2/HPC hydrogels exhibited enhanced
      adsorption performance toward methylene blue. An adsorption improvement of HPC
      hydrogel had been brought by the incorporation of HPC-MoS2 sheets. Adsorption
      kinetics was then imitated by Lagergren pseudo-first-order and pseudo-second
      order models. Adsorption isotherms were imitated by Langmuir isotherm and
      Freundlich isotherm. The photo-regeneration experiments of HPC-MoS2/HPC hydrogel
      after absorption showed that the absorbent can be activated easily by
      illumination with little loss of dye adsorbing capacity.

PMID- 28433174
TI  - Corrigendum to "Production of a low molecular weight heparin production using
      recombinant glycuronidas"[Carbohydr. Polym., 134 (2015) 151-157].

PMID- 28433175
TI  - Corrigendum to "Advances in preparation, analysis and biological activities of
      single chitooligosaccharides" [Carbohydr. Polym. 139 (2016) 178-190].

PMID- 28433176
TI  - Novel hydroxyethyl chitosan/cellulose scaffolds with bubble-like porous structure
      for bone tissue engineering.
AB  - Hydrogels fabricated from natural polysaccharides may serve as ideal scaffolds
      for tissue engineering because of their similarity to the extracellular matrices.
      In this study, novel hydrogel scaffolds with bubble-like porous structure were
      prepared from hydroxyethyl chitosan (HECS) and cellulose (CEL) by a combination
      of chemical crosslinking, particle-leaching using silicon dioxide particles as
      porogen and freeze-drying method. The morphology, compression stress-strain
      curves, wettability, and swelling and rheological behaviors of the HECS/CEL
      scaffolds were characterized by SEM, mechanical test, contact angle measurement
      and rheometer. HECS/CEL scaffolds had good comprehensive performances and could
      reach equilibrium swelling state in water within 20s. The results from in vitro
      biocompatibility evaluated using SEM, live/dead cell viability and MTT assays
      demonstrated that the HECS/CEL scaffolds could well support the attachment,
      spreading and proliferation of osteoblastic MC3T3-E1 cells and showed good
      biocompatibility. Therefore, the novel HECS/CEL scaffolds may be promising for
      bone tissue engineering applications.

PMID- 28433177
TI  - Kinetic study of thermal degradation of chitosan as a function of deacetylation
      degree.
AB  - Thermal degradation of chitosan with varying deacetylation degree (DD) ranging
      between 50 and 85% was analyzed by dynamic thermogravimetric analysis at
      different heating rates. The present study focused on the temperature range
      between 500 and 800K, above water evaporation. Thermal degradation showed a main
      degradation stage in this temperature interval with a second stage that appeared
      in the weight derivative curves as a shoulder in the high temperature side of the
      main peak with increasing intensity as the DD decreased. The Kissinger and
      isoconversional Ozawa-Flynn-Wall models were employed to evaluate the Ea of both
      thermal degradation processes. Different kinetic models were tested to computer
      simulate the thermogravimetric traces calculating the model parameters with a non
      linear least squares fitting routine. The Sestack-Berggren model allowed
      reproducing accurately the overlapping of the two degradation mechanisms and
      calculating the mass fraction lost in each of them revealing the coupling between
      the two degradation mechanisms.

PMID- 28433178
TI  - Preparation and characterization of biodegradable nanocomposites derived from
      carboxymethyl cellulose and hydroxyapatite.
AB  - Development of a cost-effective technology for extraction and quantification of
      carcinogenic and toxic organic materials which are widely used in the industry
      are critical to humans. Membrane technology received much attention and has
      already been widely used in this area. In this work, we offer a newly developed
      bio-based nanocomposite membrane for removal of bisphenol-A (BPA) from water.
      Three natural components hydroxyapatite (HAp), carboxymethyl cellulose and lysine
      as a diluent were used for making the bio-based membrane. The membrane was
      fabricated by two different methods, the conventional casting method and the
      double decomposition method. Analysis and testing results showed that, membrane
      produced by the casting method is rough, stiff and partially soluble in water.
      However, the film made by the double decomposition method is smooth, flexible,
      and has low water solubility. The physicochemical characteristics of the prepared
      membranes were determined by Fourier transform infrared spectroscopy (FT-IR) and
      thermal gravimetric analysis (TGA/DTA). The morphology and components interface
      were observed by X-ray wide angle (WAXD), scanning electron microscopy (SEM) and
      electron microscopy (SEM/FEG). The spectral and crystallographic data showed the
      presence of an effective interaction between hydroxyapatite and CMC plasticized
      with lysine. Results also show that, the particles size of the composite decrease
      as the content of CMC increases, with an increase of a 2% by weight of CMC the
      size increases by 18+/-3nm. Produced membrane composite could be classified as
      tri-functional material: it could be useful for extracting toxic material
      bisphenol A (BPA) from baby food containers; has antimicrobial and antifungal
      properties; and a valuable candidate for use in bone tissue engineering.

PMID- 28433180
TI  - Novel carboxymethyl cellulose-polyvinyl alcohol blend films stabilized by
      Pickering emulsion incorporation method.
AB  - The aim of this study was to investigate the possibility of increasing the
      antimicrobial and antioxidant properties of biodegradable active films stabilized
      via Pickering emulsions. The blend films were prepared from carboxymethyl
      cellulose (CMC) and polyvinyl alcohol (PVA), emulsified with oleic acid (OL) and
      incorporated with rosemary essential oil (REO). Formation of Pickering emulsion
      was confirmed by scanning electron microscopy (SEM), optical microscopy, mean
      droplet size and emulsion stability. Morphological, optical, physical,
      mechanical, thermal, antifungal and antioxidant properties of the films
      incorporated with different concentrations of REO (0.5, 1.5 and 3%) were
      determined. The results showed an increase in UV absorbance and elongation at
      break but, a decrease in tensile strength and thermal stability of the films.
      Interestingly, films containing REO exhibited considerable antioxidant and
      antimicrobial properties. In vitro microbial tests exhibited 100% fungal
      inhibition against Penicillium digitatum in the films containing 3% REO. In
      addition, no fungal growth were observed after 60days of storage at 25 degrees C
      in bread slices were stored with active films incorporated with 3% REO, could
      attributed to the slow and regular release of REO caused by Pickering emulsions.
      The results of this study suggest that Pickering emulsion is a very promising
      method, which significantly affects antioxidant and antimicrobial activities of
      the films.

PMID- 28433179
TI  - Isolation of cellulose nanocrystals from medium density fiberboards.
AB  - Cellulose fibers have been successfully isolated from medium density fiberboards
      (MDFs) by sodium chlorite oxidation-potassium hydroxide (NaClO2-KOH) leaching
      process, at 37.6% yield, comparable to the 39.3% and 37.3% cellulose fibers from
      eucalyptus and eucalyptus with 12% cured urea-formaldehyde (UF) resin,
      respectively. At the same sulfuric acid hydrolysis conditions (65% H2SO4, 60
      degrees C and 30min), MDF cellulose nanocrystals (CNCs) were produced at 27.5%
      yield, similar to 27.4% of CNC yield from eucalyptus with UF resin, but less than
      31.2% yield from eucalyptus. MDF CNCs were slightly thicker in lateral dimension
      (16.8+/-8.6nm), less crystalline (59% CrI), and surface esterificated
      (0.045mmol/g sulfate/CNC) than eucalyptus CNCs (11.6+/-3.9nm, 75% CrI,
      0.060mmol/g) and CNCs from eucalyptus with UF resin (14.9+/-9.1nm, 65% CrI,
      0.046mmol/g). All CNCs were free of UF resin and thermal stable. The residual
      resin in cellulose pulps hydrolyzed completely during the sulfuric acid treatment
      and contributed to the unique properties of CNCs. Therefore, CNCs derived from
      MDF are comparable to CNC from wood and promising for expanded applications.

PMID- 28433181
TI  - Effects of Scutellaria barbata polysaccharide on the proliferation, apoptosis and
      EMT of human colon cancer HT29 Cells.
AB  - A water-soluble polysaccharide SPS2p was isolated from the whole grass of
      Scutellaria barbata and SPS2p contained 53.6% carbohydrates, 38.5% uronic acid
      and 8.2% proteins. The molecular weight of SPS2p showed only one molecular weight
      distribution (2.6*104Da) and the monosaccharide composition of SPS2p showed the
      presence of arabinose, mannose, glucose and galactose at the ratio of
      1.31:1.00:3.59:1.59. The results showed that SPS2p could improve the
      proliferation inhibition rate; SPS2p could also elevate apoptosis rate, apoptosis
      index and the levels of Bax and Bak, but lower levels of Bcl-2 and FN; SPS2p
      could up-regulate the expression of E-cadherin mRNA, and down-regulate the
      expressions of N-cadherin and vimentin mRNA, and the ratio of p-AKT/AKT in HT29
      cells. These results indicate that SPS2p can inhibit the proliferation and EMT,
      and promote the apoptosis in HT29 cells, which may be related to the inhibition
      of SPS2p on the PI3K/AKT pathway.

PMID- 28433182
TI  - Vitamin D-fortified chitosan films from mushroom waste.
AB  - Brown mushroom (Agaricus bisporus) stalk bases from mushroom waste were treated
      with UV-B light to rapidly increase vitamin D2 content. Chitin was also recovered
      from this waste and converted into chitosan by N-deacetylation. FTIR spectra
      showed that the mushroom chitosan were similar to chitosan from animal sources.
      Chitosan films were prepared using high molecular weight (HW), low molecular
      weight (LW) and fungal chitosan. UV-B treated mushroom particles were also
      incorporated into fungal chitosan films. The fungal chitosan films showed similar
      density, porosity and water vapor barrier properties to the LW and HW chitosan
      films. However, fungal chitosan films were more hydrophobic and less flexible
      than the LW and HW chitosan films. Addition of mushroom particles did not
      significantly affect mechanical or water barrier properties of the fungal
      chitosan films.

PMID- 28433183
TI  - Corrigendum to "Comparative tissue distribution and excretion study of alkaloids
      from Herba Ephedrae-Radix Aconiti Lateralis extracts in rats" [J. Pharm. Biomed.
      Anal., 134 (2017) 137-142].

PMID- 28433184
TI  - The Scientifically Elite and the Clinically Expert; an editorial interface.

PMID- 28433185
TI  - Dynamic surface tension measurement for the screening of biosurfactants produced
      by Lactobacillus plantarum subsp. plantarum PTCC 1896.
AB  - Currently, screening of microbial biosurfactants (BSs) is based on their
      equilibrium surface tension values obtained using static surface tension
      measurement. However, a good surfactant should not only have a low equilibrium
      surface tension, but its dynamic surface tension (DST) should also decrease
      rapidly with time. In this study, screening of BSs produced by Lactobacillus
      plantarum subsp. plantarum PTCC 1896 (probiotic) was performed based on their DST
      values measured by Wilhelmy plate tensiometry. The relationship between DST and
      structural and functional properties (anti-adhesive activity) of the BSs was
      investigated. The results showed that the changes in the yield, productivity and
      structure of the BSs were growth medium and incubation time dependent (p<0.05).
      Structurally different BSs produced exhibited identical equilibrium surface
      tension values. However, differences among the structure/yield of the BSs were
      observed through the measurement of their DST. The considerable dependence of DST
      on the concentration and composition of the BS proteins was observed (p<0.05).
      Moreover, the anti-adhesive activity of the BS was found to be positively
      correlated with its DST. The results suggest that the DST measurement could serve
      as an efficient method for the clever screening of BSs producer/production
      condition, and consequently, for the investigation of probiotic features of
      bacteria, since the anti-adhesive activity is an important criterion of
      probiotics.

PMID- 28433187
TI  - A study of CO/syngas bioconversion by Clostridium autoethanogenum with a flexible
      gas-cultivation system.
AB  - Bioconversion of CO/syngas to produce ethanol is a novel route in bioethanol
      production, which can be accomplished by some acetogens. Specific culture vessels
      and techniques are needed to cultivate these microorganisms since they are
      anaerobic and substrates are gaseous. In this work, gas-sampling bag was applied
      as a gas-cultivation system to study CO/syngas bioconversion by Clostridium
      autoethanogenum and was demonstrated to be efficient because of its flexibility
      and excellent ability to maintain the headspace atmosphere. C. autoethanogenum
      can use CO as the sole carbon and energy source to produce ethanol, acetate as
      well as CO2. In the experimental range, higher ethanol production was favored by
      higher yeast extract concentrations, and the maximum ethanol concentration of
      3.45g/L was obtained at 1.0g/L of yeast extract. Study with various bottled gases
      showed that C. autoethanogenum preferred to use CO other than CO2 and produced
      the highest level of ethanol with 100% CO as the substrate. C. autoethanogenum
      can also utilize biomass-generated syngas (36.2% CO, 23.0% H2, 15.4% CO2, 11.3%
      N2), but the process proceeded slowly and insufficiently due to the presence of
      O2 and C2H2. In our study, C. autoethanogenum showed a better performance in the
      bioconversion of CO to ethanol than Clostridium ljungdahlii, a strain which has
      been most studied, and for both strains, ethanol production was promoted by
      supplementing 0.5g/L of acetate.

PMID- 28433186
TI  - Characterization and thermal inactivation kinetics of highly thermostable ramie
      leaf beta-amylase.
AB  - We characterized ramie leaf beta-amylase, and determined its thermostability and
      kinetic parameters. The enzyme was purified 53-fold using ammonium sulfate
      fractionation (40-60% saturation), anion exchange chromatography on DEAE
      cellulose and gel permeation chromatography on Superdex-200. The purified enzyme
      was identified as beta-amylase with molecular mass of 42kD. The enzyme displayed
      Km and kcat values for soluble potato starch of 1.1mg/mL and 7.8s-1,
      respectively. The enzyme had a temperature optimum of 65 degrees C, and its
      activity at 70 degrees C was 92% of that at the optimal temperature after a 15
      min incubation. Furthermore, enzyme activity was stable during treatment at 55
      degrees C for 60min but was inactivated rapidly at >75 degrees C. This thermal
      behavior indicates that ramie leaf beta-amylase has excellent intermediate
      temperature-stable enzyme properties for the baking and bio-industries.
      Inactivation of the enzyme followed first-order kinetics in the range of 55-80
      degrees C. The enthalpy change of thermal inactivation (DeltaH?), DeltaG?, and
      DeltaS? were 237.2kJ/mol, 107.7kJ/mol, and 0.39kJ/molK at 333K, respectively. The
      D-value at 65 degrees C (=110min) and the z-value (=9.4 degrees C) are given for
      food processing.

PMID- 28433188
TI  - Metabolic engineering of Saccharomyces cerevisiae for production of spermidine
      under optimal culture conditions.
AB  - Spermidine is a polyamine compound exhibiting important biological activities,
      such as increasing lifespan, inflammation reduction, and plant growth control. As
      such, many applications of spermidine as a bio-modulating agent are anticipated.
      However, sustainable and scalable production of spermidine has not been achieved
      yet. Therefore, construction of a spermidine production system using
      Saccharomyces cerevisiae was attempted in this study. In order to secrete
      spermidine into fermentation broth, TPO1 coding for the polyamine transporter was
      overexpressed in an engineered S. cerevisiae strain capable of accumulating high
      concentrations of spermidine. Through optimization of fermentation conditions,
      the resulting strain (OS123/pTPO1) produced 63.6mg/l spermidine with a yield of
      1.3mg spermidine/g glucose. However, we observed that spermidine production was
      repressed in the presence of glucose. To circumvent this problem, the genetic
      modifications for overproducing spermidine were introduced into an engineered S.
      cerevisiae capable of fermenting xylose. In a fed-batch fermentation using a
      mixture of glucose and xylose, the resulting strain (SR8 OS123/pTPO1) produced
      224mg/l spermidine with a yield of 2.2mg spermidine/g sugars. These results
      suggest that engineered yeast constructed in this study can be employed for the
      production of spermidine.

PMID- 28433189
TI  - Synergic regulation of redox potential and oxygen uptake to enhance production of
      coenzyme Q10 in Rhodobacter sphaeroides.
AB  - The physiological role of Coenzyme Q10 (CoQ10) as an electron carrier suggests
      its association with redox potential. Overexpression of glyceraldehyde-3
      phosphate dehydrogenase type I (gapA-1) in Rhodobacter sphaeroides elevated the
      NADH/NAD+ ratio and meanwhile enhanced the CoQ10 content by 58%, but at the
      sacrifice of biomass. On the other hand, Vitreoscilla hemoglobin was
      heterologously expressed to enhance the oxygen uptake ability of the cells,
      leading to 127% improvement of biomass. Subsequent coexpression of gapA-1 and vgb
      resulted in a CoQ10 titer of 83.24mg/L, representing 71% improvement as compared
      to the control strain RspMCS. When gapA-1 and vgb genes were co-expressed in a
      previously created strain RspMQd [1], 163.5mg/L of CoQ10 was produced. Finally,
      600mg/L of CoQ10 production was achieved in fed-batch fermentation. These results
      demonstrated the synergic effect of redox potential regulation and oxygen uptake
      improvement on enhancing CoQ10 production in R. sphaeroides.

PMID- 28433190
TI  - Evaluation of the effects of isolated lignin on enzymatic hydrolysis of
      cellulose.
AB  - The different physical and chemical properties of lignin might have various
      effects on the enzymatic hydrolysis of lignocellulosic substrates. In this study,
      the influence of lignin on enzymatic digestibility of cellulose was assessed.
      Addition of 20% (4g/L) isolated enzymatic lignin (lignin 2 and 3) and kraft
      lignin (lignin 4) resulted in 5-20% drop of glucose yield, depending on lignin
      sources. The inhibitory effect of lignin was abated as the enzyme loading
      increased from 10 to 20FPU/g dry substrate. However, the increasing lignin amount
      to 40% (8g/L) did not appear to further decrease the cellulose hydrolysis
      efficiency. Ethanol lignin (lignin 1) and calcium lignosulfonate (lignin 5) had
      no negative effect on the enzymatic hydrolysis of cellulose at cellulase loading
      of 10 or 20FPU/g dry substrate, the increasing lignin content to 40% presented
      6.2% increase of glucose yield. The results indicated that different lignin had
      significantly influence on the enzymatic hydrolysis, which was confirmed by
      analysis in chemical composition, elemental analysis, functionality, and
      thermogravimetry.

PMID- 28433191
TI  - Enzymatic synthesis of isomaltotriose palmitate and evaluation of its emulsifying
      property.
AB  - Enzymatic syntheses of oligosaccharide fatty acid esters are important owing to
      their wide range of industrial applications in the food, cosmetic, and
      pharmaceutical industries. Transesterification of isomaltotriose and palmitic
      acid vinyl ester, catalyzed by the metalloprotease thermolysin, was performed in
      organic solvents. The process parameters (reaction time and temperature) were
      optimized to achieve the highest yield of isomaltotriose palmitate (IP). The
      water content of the reaction system played a key role in the acylation of
      isomaltotriose. Dimethyl sulfoxide was thought to be the most suitable reaction
      medium by taking the degree of substitution of the modified isomaltotriose into
      account. The optimum reaction time, temperature, water content, and enzyme
      concentration were 24h, 45 degrees C, 40%, and 0.05%, respectively, under which
      the product yield was as high as 89.7%. The enzyme operational stability study
      showed that thermolysin retained 51.5% of its initial activity for the synthesis
      of IP (even after repeated use for 72h). Moreover, test results showed that the
      emulsifying capacity and emulsion stability of IP are 107.5mL oil/g ester and
      16.3%, respectively.

PMID- 28433192
TI  - A Zymogram technique for preliminary screening and characterization of feruloyl
      esterases.
AB  - We report here, for the first time, a zymogram technique designed for rapid
      screening of feruloyl esterase using ethyl ferulate as enzyme substrate and
      casein precipitation as enzyme activity indicator.

PMID- 28433194
TI  - Keeping your teeth and mouth safe.

PMID- 28433193
TI  - Regulation of the catalytic behavior of pullulanases chelated onto nickel (II)
      modified magnetic nanoparticles.
AB  - Chelating of pullulanases onto nickel (II)-modified magnetic nanoparticles
      results in one-step purification and immobilization of pullulanase, and
      facilitates the commercial application of pullulanase in industrial scale. To
      improve the catalytic behavior, especially the operational stability, of the
      nanocatalyst in consecutive batch reactions, we prepared various iminodiacetic
      acid-modified magnetic nanoparticles differed in surface polarity and spacer
      length, on which the His6-tagged pullulanases were chelated via nickel ions, and
      then studied the correlation between the MNPs surface property and the
      corresponding catalyst behavior. When pullulanases were chelated onto the surface
      modified MNPs, the thermostability of all pullulanase derivatives were lower than
      that of free counterpart, being not relevant to the protein orientation guided by
      the locality of the His6-tag, but related to the MNPs basal surface polarity and
      the grafted spacer length. After chelating of pullulanases onto MNPs, there were
      changes observed in the pH-activity profile and the apparent Michaelis constant
      toward pullulan. The changing tendencies were mainly dependent on the His6-tagged
      pullulanase orientation, and the changing extents were tuned by the spacer
      length. The reusability of pullulanase immobilized by N-terminal His6-tag was
      higher than that of pullulanase immobilized by C-terminal His6-tag. Moreover, the
      reusability of the immobilized pullulanase tested increased till grafting
      polyether amine-400 as spacer-arm, therefore the N-terminal His6-tagged
      pullulanase chelating MNPs grafted polyether amine-400 gave the best reusability,
      which retained 60% of initial activity after 18 consecutive cycles with a total
      reaction time of 9h. Additionally, the correlation analysis of the catalyst
      behaviors indicated that the reusability was independent from other catalytic
      properties such as thermostability and substrate affinity. All the results
      revealed that the catalyst behavior can be mainly controlled by the His6-tagged
      pullulanase orientation than by the MNPs surface property which can tune the
      catalyst function.

PMID- 28433195
TI  - Predicting successful dental examinations for children with autism spectrum
      disorder in the context of a dental desensitization program.
AB  - BACKGROUND: The authors evaluated the effectiveness of a dental desensitization
      program for children with autism spectrum disorder (ASD) and determined
      characteristics associated with a successful dental examination. METHODS: The
      authors performed a retrospective review of clinical behavioral data and previsit
      questionnaires for 168 children with ASD who attended a university-based dental
      desensitization program. Data elements included demographic, treatment, and
      behavioral characteristics. The primary outcome was receiving a minimal threshold
      examination (MTE) while seated in a dental chair. RESULTS: An MTE was achieved
      for 77.4% of all children within 1 to 2 visits and 87.5% in 5 visits or less.
      Several factors predicted a successful dental examination: ability to be involved
      in group activities (relative risk [RR], 1.18; P = .02), ability to communicate
      verbally (RR, 1.17; P < .01), understanding of most language (RR, 1.14; P = .02),
      moderate versus severe caregiver-rated ASD severity (RR, 1.24; P = .04), and
      ability to dress self (RR, 1.27; P = .04). CONCLUSIONS: Desensitization was
      effective in achieving an MTE for most children. Those with characteristics
      consistent of a milder presentation of ASD were more likely to be successful.
      PRACTICAL IMPLICATIONS: Desensitization can be a successful approach to providing
      dental care for children with ASD.

PMID- 28433196
TI  - Relational information moderates approach-avoidance instruction effects on
      implicit evaluation.
AB  - Previous research demonstrated that instructions to approach one stimulus and
      avoid another stimulus can result in a spontaneous or implicit preference for the
      former stimulus. In the current study, we tested whether the effect of approach
      avoidance instructions on implicit evaluation depends on the relational
      information embedded in these instructions. Participants received instructions
      that they would move towards a certain non-existing word and move away from
      another non-existing word (self-agent instructions) or that one non-existing word
      would move towards them and the other non-existing word would move away from them
      (stimulus-agent instructions). Results showed that self-agent instructions
      produced stronger effects than stimulus-agent instructions on implicit
      evaluations of the non-existing words. These findings support the idea that
      propositional processes play an important role in effects of approach-avoidance
      instructions on implicit evaluation and in implicit evaluation in general.

PMID- 28433197
TI  - [What is the place of the combinations for immunotherapy with chemotherapy or
      with other immune checkpoint inhibitors?]
AB  - Immune checkpoint blockade by the use of anti-PD(L)1 or anti-CTLA4 antibodies can
      induce long lasting disease response and maybe cure in a lot of advanced cancer
      patients. This ongoing immunotherapy revolution has given new hope to cancer
      patients and oncologists. However, still the majority of cancer patients do not
      respond to immune checkpoint blockade and novel therapeutical possibilities are
      being tested in several clinical trials. One of the possibilities to enhance
      responses to immune checkpoint blockade is the combination with chemotherapy or
      with other immune checkpoint blockade molecules. In this review, we explore the
      preclinical rational for this synergism and the potential consequences for
      immunotherapy in oncology.

PMID- 28433198
TI  - Tumor promoting role of anti-tumor macrophages in tumor microenvironment.
AB  - Recent advances in tumor biology demand detailed analysis of the complex
      interaction of tumor cells with their adjacent microenvironment (tumor stroma) to
      understand the various mechanisms involved in tumor growth and metastasis.
      Mononuclear phagocytes or macrophages, a type of innate immune cells, defend the
      organism against infection and injury. On the otherhand, tumor associated
      macrophages (TAMs) constitute a significant part of the tumor-infiltrating immune
      cells, have been linked to the growth, angiogenesis, and metastasis of a variety
      of cancers, most likely through polarization of TAMs to the M2 (alternative)
      phenotype. Clinical and experimental evidences have shown that cancer tissues
      with high infiltration of TAMs are associated with poor patient prognosis and
      resistance to therapies, thus, targeting of TAMs in tumors is considered as a
      promising immunotherapeutic strategy. Depletion of M2 TAMs or 're-education' of
      them as anti-tumor effectors might contribute significantly to the search of new
      modalities in anti-cancer treatments. Basic questions on the factors responsible
      for homing of macrophages in tumors, mechanism of conversion of M1 to M2 TAMs,
      their functionality and, finally, the possible ways to target M2 TAMs are
      discussed.

PMID- 28433199
TI  - Glycoprotein non-metastatic melanoma protein b (Gpnmb) is highly expressed in
      macrophages of acute injured kidney and promotes M2 macrophages polarization.
AB  - Acute kidney injury (AKI) is an increasingly common disorder that is strongly
      linked to short- and long-term morbidity and mortality. During AKI process,
      macrophages, one of the important immune response cells, can polarize into M1 and
      M2 subtype from M0 subtype. It is well-known that M1 macrophages play a pro
      inflammatory role while M2 macrophages play an anti-inflammatory role.
      Glycoprotein non-metastatic melanoma protein b (Gpnmb) is a glycosylated
      transmembrane protein highly expressed in numerous cells, including osteoblasts,
      dendritic cells and macrophages. Gpnmb serves as a negative regulator of
      inflammation in macrophages and has a protective effect on injuries. In acute
      kidney injury, the macrophage has been shown diverse roles depending on different
      phenotype. This study provided gene expression and protein expression evidence
      that Gpnmb was highly expressed in M2 macrophages in the damaged areas of kidney
      after ischemia-reperfusion injury. Then, we successful isolated and culture mouse
      bone marrow-derived macrophages (BMMphi) and found that Gpnmb showed different
      expression levels in M0, M1 and M2 BMMphi: lowest in M1, highest in M2. After
      knocking down Gpnmb with si-Gpnmb, BMMphi M2 polarization and secretion of anti
      inflammatory cytokines IL-10 and TGF-beta were inhibited, while M1 polarization
      and secretion of proinflammatory cytokines IL-1beta and TNF-alpha were promoted.
      Moreover, IL-4-STAT6 pathway was involved in the promotion of M2 polarization by
      Gpnmb. Taken together, Gpnmb may serve as a potential biomarker of AKI and play a
      protective role against the AKI by modulating the polarization of macrophage.

PMID- 28433200
TI  - The case against performing pleural biopsies for the aetiological diagnosis of
      exudates.
AB  - In most cases, the etiological diagnosis of pleural exudates does not require a
      pleural biopsy. However, when it is considered necessary, the biopsy should
      seldom be conducted using invasive methods such as thoracoscopy. Two paradigmatic
      examples are pleural tuberculosis and malignant effusions. In many centres,
      pleural fluid adenosine deaminase measurement has replaced closed pleural
      biopsies in the diagnosis of tuberculosis. Similarly, pathological and molecular
      studies on pleural fluid cell blocks or alternatively, image-guided pleural
      biopsies have drastically reduced the need for thoracoscopy.

PMID- 28433201
TI  - Humoral primary immunodeficiency diseases: clinical overview and chest high
      resolution computed tomography (HRCT) features in the adult population.
AB  - Humoral primary immunodeficiency diseases (hPIDs) are a heterogeneous group of
      hereditary disorders resulting in abnormal susceptibility to infections of the
      sinopulmonary tract. Some of these conditions (e.g., common variable
      immunodeficiency disorders [CVID]) imply a number of non-infectious thoracic
      complications such as non-infectious airway disorders, diffuse lung parenchymal
      diseases, and neoplasms. Chest high-resolution computed tomography (HRCT) is a
      key imaging tool to characterise and quantify the extent of underlying thoracic
      involvement, as well as to direct and monitor treatment. The aims of this review
      are to provide a brief clinical overview of hPIDs and describe the related chest
      HRCT imaging features in the adult population, with a special focus on CVID and
      its complications.

PMID- 28433202
TI  - Tinea Faciei: Challenges in the Diagnosis.

PMID- 28433203
TI  - The Limitations of Transforming Very High Body Mass Indexes into z-Scores among
      8.7 Million 2- to 4-Year-Old Children.
AB  - OBJECTIVE: To examine the associations among several body mass index (BMI)
      metrics (z-scores, percent of the 95th percentile (%BMIp95) and BMI minus 95th
      percentile (DeltaBMIp95) as calculated in the growth charts from the Centers for
      Disease Control and Prevention (CDC). It is known that the widely used BMI z
      scores (BMIz) and percentiles calculated from the growth charts can differ
      substantially from those that directly observed in the data for BMIs above the
      97th percentile (z = 1.88). STUDY DESIGN: Cross-sectional analyses of 8.7 million
      2- to 4-year-old children who were examined from 2008 through 2011 in the CDC's
      Pediatric Nutrition Surveillance System. RESULTS: Because of the transformation
      used to calculate z-scores, the theoretical maximum BMIz varied by >3-fold across
      ages. This results in the conversion of very high BMIs into a narrow range of z
      scores that varied by sex and age. Among children with severe obesity, levels of
      BMIz were only moderately correlated (r ~ 0.5) with %BMIp95 and DeltaBMIp95.
      Among these children with severe obesity, BMIz levels could differ by more than 1
      SD among children who had very similar levels of BMI, %BMIp95 and DeltaBMIp95 due
      to differences in age or sex. CONCLUSIONS: The effective upper limit of BMIz
      values calculated from the CDC growth charts, which varies by sex and age,
      strongly influences the calculation of z-scores for children with severe obesity.
      Expressing these very high BMIs relative to the CDC 95th percentile, either as a
      difference or percentage, would be preferable to using BMI-for-age, particularly
      when assessing the effectiveness of interventions.

PMID- 28433204
TI  - [Post operative visual loss after cervical laminectomy in prone position].
AB  - Postoperative visual loss is a rare and devastating complication. The estimated
      incidence is 0.01-1% after non ocular surgery. It has been reported after spine,
      cardiac and head and neck surgeries. We report a patient who was operated for
      cervical laminectomy in prone position and complained of loss of vision in one
      eye postoperatively. He was thoroughly investigated after visual loss. The case
      was diagnosed as central retinal artery occlusion (CRAO) of the left eye. Here we
      consider the potential etiological factors causing this unilateral loss of vision
      and try to suggest strategies to reduce the incidence of the complication in
      spinal surgery.

PMID- 28433205
TI  - Federal research priorities in child abuse and neglect research: A commentary on
      multi-site research networks.
AB  - The National Institutes of Health has a long history of supporting investigator
      initiated child abuse research, including risk-factor studies on prevalence,
      course and consequences of child abuse and neglect. These studies laid the ground
      work for prevention research as well as the development and testing of
      therapeutic interventions. The newly established Pediatric Trauma and Critical
      Illness Branch at the Eunice Kennedy Shriver National Institute of Child Health
      and Human Development represents a new opportunity to call attention to the need
      for greater collaboration among researchers to build on prior work, pursue
      complex lines of inquiry, address more medically focused research and new
      clinical questions that will heighten the awareness of the unique needs for
      treatment and care of abused children.

PMID- 28433206
TI  - Efficacy and safety of rivaroxaban versus warfarin in patients from mainland
      China with nonvalvular atrial fibrillation: A subgroup analysis from the ROCKET
      AF trial.
AB  - BACKGROUND: The ROCKET AF study evaluated once-daily rivaroxaban versus dose
      adjusted warfarin for the prevention of stroke and systemic embolism in patients
      with atrial fibrillation (AF). In this analysis, we compared rivaroxaban with
      warfarin in patients with AF from China, East Asia, and the rest of the world
      (ROW). METHODS AND RESULTS: We assessed baseline demographics and interaction of
      treatment effects of rivaroxaban versus warfarin among patients from mainland
      China, other East Asian countries, and ROW. Of the 14,236 patients enrolled in
      the per-protocol population, 495 were from mainland China, 433 from other East
      Asian regions, and 13,308 from the rest of the world (ROW). At baseline, patients
      from China had significantly higher rates of previous stroke/transient ischemic
      attack (TIA) compared with patients from other East Asian regions and ROW (79.6%,
      44.6%, 51.6% respectively; p<0.0001) and lower rates of VKA use (33.7%, 66.7%,
      63.4%, respectively; p<0.0001). The rates of stroke or systemic embolism among
      those on warfarin while on treatment was 5.23% in patients from China, 1.82% in
      those from other East Asian regions, and 2.07% from ROW; on rivaroxaban, the
      rates were 2.29% in patients from China, 1.86% in those from other east Asian
      regions, and 1.67% from ROW. There were no significant treatment-by-region
      interactions for any efficacy or safety outcome (all p>0.12). Numerically higher
      rates of intracranial bleeding were seen in patients from China receiving
      warfarin versus rivaroxaban. CONCLUSIONS: In patients from China, rates of
      intracranial hemorrhage were numerically lower among those receiving rivaroxaban
      and consistent with the overall trial. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

PMID- 28433207
TI  - Correlation of frontal sinus recess anatomy with ethnicity, gender, and
      pathology.
AB  - PURPOSE: Research on frontal sinus cells has been conflicting regarding
      relationship between frontal sinus cells and frontal sinus disease. There are no
      published studies regarding gender differences in frontal sinus disease. No
      comparisons between African Americans and Caucasians and frontal sinus disease
      have been published. This study attempts to define the above relationships as
      well as the relationship between number and types of cells and disease. METHODS:
      A retrospective chart review was performed on sinus CT scans done from 2003 to
      2011 at an academic medical center. Exclusion criteria included previous frontal
      sinus surgery, sinus malignancy, obvious trauma, congenital anomalies, and poor
      quality of scan. Number and type of frontal cells were recorded for 602 scans.
      Statistical analysis performed demographic comparisons and compared number and
      types of cells to evidence of disease. RESULTS: Males were more likely than
      females to have frontal sinus disease. Patients with Type 3 and Type 4 cells were
      more likely to have disease. No significant ethnic related differences in disease
      were found using a multivariate logistic regression model. Total number of cells
      did not significantly affect likelihood of disease. CONCLUSIONS: This is one of
      the largest collections of data on frontal sinus cells as predictors of frontal
      sinus disease. These results suggest that gender and certain types of cells
      affect likelihood of disease. This study is the first to demonstrate a lack of
      difference in disease in African Americans and Caucasians. These results are
      significant regarding gender, race, number and type of cells as predictors of
      disease.

PMID- 28433208
TI  - Elucidating the fate of a mixed toluene, DHM, methanol, and i-propanol plume
      during in situ bioremediation.
AB  - Organic pollutants such as solvents or petroleum products are widespread
      contaminants in soil and groundwater systems. In-situ bioremediation is a
      commonly used remediation technology to clean up the subsurface to eliminate the
      risks of toxic substances to reach potential receptors in surface waters or
      drinking water wells. This study discusses the development of a subsurface model
      to analyse the performance of an actively operating field-scale enhanced
      bioremediation scheme. The study site was affected by a mixed toluene,
      dihydromyrcenol (DHM), methanol, and i-propanol plume. A high-resolution, time
      series of data was used to constrain the model development and calibration. The
      analysis shows that the observed failure of the treatment system is linked to an
      inefficient oxygen injection pattern. Moreover, the model simulations also
      suggest that additional contaminant spillages have occurred in 2012. Those
      additional spillages and their associated additional oxygen demand resulted in a
      significant increase in contaminant fluxes that remained untreated. The study
      emphasises the important role that reactive transport modelling can play in data
      analyses and for enhancing remediation efficiency.

PMID- 28433209
TI  - Practical recommendations for the management of cardiovascular risk associated
      with atherogenic dyslipidemia, with special attention to residual risk. Spanish
      adaptation of a European Consensus of Experts.
AB  - This document has discussed clinical approaches to managing cardiovascular risk
      in clinical practice, with special focus on residual cardiovascular risk
      associated with lipid abnormalities, especially atherogenic dyslipidaemia (AD). A
      simplified definition of AD was proposed to enhance understanding of this
      condition, its prevalence and its impact on cardiovascular risk. AD can be
      defined by high fasting triglyceride levels (>=2.3mmol/L / >=200mg/dL) and low
      high-density lipoprotein cholesterol (HDL-c) levels (<=1,0 / 40 and <=1,3mmol/L /
      50mg/dL in men and women, respectively) in statin-treated patients at high
      cardiovascular risk. The use of a single marker for the diagnosis and treatment
      of AD, such as non-HDL-c, was advocated. Interventions including lifestyle
      optimization and low density lipoprotein (LDL) lowering therapy with statins (+/
      ezetimibe) are recommended by experts. Treatment of residual AD can be performed
      with the addition of fenofibrate, since it can improve the complete lipoprotein
      profile and reduce the risk of cardiovascular events in patients with AD. Others
      clinical condictions in which fenofibrate may be prescribed include patients with
      very high TGs (>=5.6mmol/L / 500mg/dL), patients who are intolerant or resistant
      to statins, and patients with AD and at high cardiovascular risk. The fenofibrate
      statin combination was considered by the experts to benefit from a favorable
      benefit-risk profile. In conclusion, cardiovascular experts adopt a multifaceted
      approach to the prevention of atherosclerotic cardiovascular disease, with
      lifestyle optimization, LDL-lowering therapy and treatment of AD with fenofibrate
      routinely used to help reduce a patient's overall cardiovascular risk.

PMID- 28433210
TI  - Non-Tuberculous Mycobacteria. An Emerging Threat?
AB  - INTRODUCTION AND OBJECTIVE: Non-tuberculous mycobacteria (NTM) isolates are
      becoming more common. The main objective of our study was to establish the number
      and diversity of NTM species in our region and their distribution according to
      the source sample, age and gender of the patients, and to analyse clinically
      significant isolates. METHODOLOGY: Prospective study of all NTM isolated in
      Asturias from 2005 to 2012. Samples were processed following internationally
      accepted guidelines. Statistical analysis was based on Fisher's exact test for
      2*2 contingency tables. RESULTS: A total of 3,284 mycobacteria were isolated:
      1,499 Mycobacterium tuberculosis complex (MTB) and 1,785 NTM.During the study,
      NTM isolation rates increased while MTB isolation decreased. NTM were more
      frequent in men (P<.001). M.gordonae was the most frequently isolated species but
      did not cause disease in any case. NTM isolates from 212 patients were associated
      with clinically significant disease (17.1%). M.kansasii and M.avium were most
      commonly associated with disease. The number of M.kansasii isolates from men was
      statistically significant (P<.01). CONCLUSIONS: In our study, NTM isolates
      increased by 35%, compared with a 21% decline in cases of MTB. Both isolation of
      NTM and clinically significant cases were more common in men. Only 17.1% of NTM
      isolates were associated with disease, most commonly M.avium complex and
      M.kansasii.

PMID- 28433211
TI  - Adverse Events During a Randomized Trial of Ketamine Versus Co-Administration of
      Ketamine and Propofol for Procedural Sedation in a Pediatric Emergency
      Department.
AB  - BACKGROUND: The co-administration of ketamine and propofol (CoKP) is thought to
      maximize the beneficial profile of each medication, while minimizing the
      respective adverse effects of each medication. OBJECTIVE: Our objective was to
      compare adverse events between ketamine monotherapy (KM) and CoKP for procedural
      sedation and analgesia (PSA) in a pediatric emergency department (ED). METHODS:
      This was a prospective, randomized, single-blinded, controlled trial of KM vs.
      CoKP in patients between 3 and 21 years of age. The attending physician
      administered either ketamine 1 mg/kg i.v. or ketamine 0.5 mg/kg and propofol 0.5
      mg/kg i.v. The physician could administer up to three additional doses of
      ketamine (0.5 mg/kg/dose) or ketamine/propofol (0.25 mg/kg/dose of each). Adverse
      events (e.g., respiratory events, cardiovascular events, unpleasant emergence
      reactions) were recorded. Secondary outcomes included efficacy, recovery time,
      and satisfaction scores. RESULTS: Ninety-six patients were randomized to KM and
      87 patients were randomized to CoKP. There was no difference in adverse events or
      type of adverse event, except nausea was more common in the KM group. Efficacy of
      PSA was higher in the KM group (99%) compared to the CoKP group (90%). Median
      recovery time was the same. Satisfaction scores by providers, including nurses,
      were higher for KM, although parents were equally satisfied with both sedation
      regimens. CONCLUSIONS: We found no significant differences in adverse events
      between the KM and CoKP groups. While CoKP is a reasonable choice for pediatric
      PSA, our study did not demonstrate an advantage of this combination over KM.

PMID- 28433212
TI  - Comparison between piezoelectric surgery and conventional saw in sagittal split
      osteotomies: a systematic review.
AB  - A systematic review of the advantages and disadvantages of piezoelectric surgery
      in comparison with conventional saws for sagittal split osteotomy (SSO) was
      performed. Relevant studies published in the last 10 years were identified
      through a search of the PubMed/MEDLINE, Science Direct, and Embase databases and
      assessed against predetermined eligibility criteria. The initial search resulted
      in 1736 articles. After applying the inclusion and exclusion criteria, 12
      articles remained. A total of 799 patients with an average age of 27.5 years
      underwent SSO performed using a saw or ultrasonic device. Results showed that it
      took longer to perform the osteotomies using an ultrasonic device than using a
      conventional saw. At >=6 months of follow-up, neurosensory disturbance was seen
      in 4.7% of patients who underwent piezoelectric surgery versus 61.6% of patients
      who underwent surgery in which a conventional saw was used. It was found that the
      use of piezoelectric surgery in SSO leads to the best outcome regarding
      neurosensory disturbance when compared to conventional saws (P=0.04) at >=6
      months of follow-up. Further studies are required for the evaluation of the other
      clinical parameters assessed.

PMID- 28433213
TI  - Three-dimensional surgical modelling with an open-source software protocol: study
      of precision and reproducibility in mandibular reconstruction with the fibula
      free flap.
AB  - Very few surgical teams currently use totally independent and free solutions to
      perform three-dimensional (3D) surgical modelling for osseous free flaps in
      reconstructive surgery. This study assessed the precision and technical
      reproducibility of a 3D surgical modelling protocol using free open-source
      software in mandibular reconstruction with fibula free flaps and surgical guides.
      Precision was assessed through comparisons of the 3D surgical guide to the
      sterilized 3D-printed guide, determining accuracy to the millimetre level.
      Reproducibility was assessed in three surgical cases by volumetric comparison to
      the millimetre level. For the 3D surgical modelling, a difference of less than
      0.1mm was observed. Almost no deformations (<0.2mm) were observed post-autoclave
      sterilization of the 3D-printed surgical guides. In the three surgical cases, the
      average precision of fibula free flap modelling was between 0.1mm and 0.4mm, and
      the average precision of the complete reconstructed mandible was less than 1mm.
      The open-source software protocol demonstrated high accuracy without
      complications. However, the precision of the surgical case depends on the
      surgeon's 3D surgical modelling. Therefore, surgeons need training on the use of
      this protocol before applying it to surgical cases; this constitutes a
      limitation. Further studies should address the transfer of expertise.

PMID- 28433215
TI  - Meta-Analysis of Randomized Controlled Trials of Percutaneous Coronary
      Intervention With Drug-Eluting Stents Versus Coronary Artery Bypass Grafting in
      Left Main Coronary Artery Disease.
AB  - Few randomized controlled trials (RCTs) and observational studies had shown
      acceptable short-term efficacy and safety of percutaneous coronary intervention
      (PCI) with drug-eluting stents (DES) compared with coronary artery bypass
      grafting (CABG) in selected patients with left main coronary artery disease
      (LMCAD). We aimed to evaluate long-term outcomes of PCI using DES compared with
      CABG in patients with LMCAD. On November 1, 2016, we searched available databases
      for published RCTs directly comparing DES PCI with CABG in patients with LMCAD.
      Odds ratios (ORs) were used as the metric of choice for treatment effects using a
      random-effects model. I-squared index was used to assess heterogeneity across
      trials. Prespecified end points were all-cause mortality, cardiovascular
      mortality, myocardial infarction (MI), stroke, and repeat revascularization at
      maximal available follow-up. We identified 5 RCTs including a total of 4,595
      patients, with a median follow-up of 60 months. The risk of all-cause mortality
      (OR 1.01; 95% confidence interval [CI] 0.76 to 1.34) and cardiovascular mortality
      (OR 1.02; 95% CI 0.73 to 1.42) were comparable between PCI with DES and CABG.
      Similarly, there were no statistically significant differences between PCI with
      DES and CABG for MI (OR 1.45; 95% CI 0.87 to 2.40) and stroke (OR 0.87; 95% CI
      0.38 to 1.98). Conversely, repeat revascularization was significantly higher with
      PCI compared with CABG (OR 1.82; 95% CI 1.51 to 2.21). In conclusion, in patients
      with LMCAD, PCI with DES appears to be a viable alternative to CABG at long-term
      follow-up, with similar risks of ischemic adverse events (mortality, MI, and
      stroke) but a higher risk of repeat revascularization.

PMID- 28433214
TI  - Maturational Patterns of Systolic Ventricular Deformation Mechanics by Two
      Dimensional Speckle-Tracking Echocardiography in Preterm Infants over the First
      Year of Age.
AB  - BACKGROUND: The aim of this study was to determine the maturational changes in
      systolic ventricular strain mechanics by two-dimensional speckle-tracking
      echocardiography in extremely preterm neonates from birth to 1 year of age and
      discern the impact of common cardiopulmonary abnormalities on the deformation
      measures. METHODS: In a prospective multicenter study of 239 extremely preterm
      infants (<29 weeks gestation at birth), left ventricular (LV) global longitudinal
      strain (GLS) and global longitudinal systolic strain rate (GLSRs),
      interventricular septal wall (IVS) GLS and GLSRs, right ventricular (RV) free
      wall longitudinal strain and strain rate, and segmental longitudinal strain in
      the RV free wall, LV free wall, and IVS were serially measured on days 1, 2, and
      5 to 7, at 32 and 36 weeks postmenstrual age, and at 1 year corrected age (CA).
      Premature infants who developed bronchopulmonary dysplasia or had
      echocardiographic findings of pulmonary hypertension were analyzed separately.
      RESULTS: In uncomplicated preterm infants (n = 103 [48%]), LV GLS and GLSRs
      remained unchanged from days 5 to 7 to 1 year CA (P = .60 and P = .59). RV free
      wall longitudinal strain, RV free wall longitudinal strain rate, and IVS GLS and
      GLSRs significantly increased over the same time period (P < .01 for all
      measures). A significant base-to-apex (highest to lowest) segmental longitudinal
      strain gradient (P < .01) was seen in the RV free wall and a reverse apex-to-base
      gradient (P < .01) in the LV free wall. In infants with bronchopulmonary
      dysplasia and/or pulmonary hypertension (n = 119 [51%]), RV free wall
      longitudinal strain and IVS GLS were significantly lower (P < .01), LV GLS and
      GLSRs were similar (P = .56), and IVS segmental longitudinal strain persisted as
      an RV-dominant base-to-apex gradient from 32 weeks postmenstrual age to 1 year
      CA. CONCLUSIONS: This study tracks the maturational patterns of global and
      regional deformation by two-dimensional speckle-tracking echocardiography in
      extremely preterm infants from birth to 1 year CA. The maturational patterns are
      ventricular specific. Bronchopulmonary dysplasia and pulmonary hypertension leave
      a negative impact on RV and IVS strain, while LV strain remains stable.

PMID- 28433216
TI  - Implications of Alternative Hepatorenal Prognostic Scoring Systems in Acute Heart
      Failure (from DOSE-AHF and ROSE-AHF).
AB  - Because hepatic dysfunction is common in patients with heart failure (HF), the
      Model for End-Stage Liver Disease (MELD) may be attractive for risk
      stratification. Although alternative scores such as the MELD-XI or MELD-Na may be
      more appropriate in HF populations, the short-term clinical implications of these
      in patients with acute heart failure (AHF) are unknown. The MELD-XI and MELD-Na
      were calculated at baseline in 453 patients with AHF in the DOSE-AHF and ROSE-AHF
      trials. The correlations and associations for each score with cardiorenal
      biomarkers, short-term end points at 72 hours including worsening renal function
      and clinical events to 60 days were determined. The median MELD-XI and MELD-Na
      was 16 and 17, respectively. Both were correlated with baseline cystatin C, amino
      terminus pro-B-type natriuretic peptide, and plasma renin activity (p <0.003 for
      all). MELD-XI <=16 and MELD-Na <=17 were associated with a slight increase in
      cystatin C (p <0.02 for both), higher diuretic efficiency (p <0.001 for both),
      but not with change in global visual assessment scores (p >0.05 for both) at 72
      hours. Neither score was associated with worsening renal function or worsening HF
      (p >0.05 for all). Similarly, both the MELD-XI and MELD-Na were not associated
      with 60-day death/any rehospitalization and 60-day death/HF rehospitalization in
      adjusted analyses when analyzes as a dichotomous or continuous variable (p >0.05
      for all). In conclusion, the alternative MELD scores correlated with baseline
      cardiorenal biomarkers, and lower baseline MELD scoring was associated with
      higher diuretic efficiency and a slight increase in cystatin C through 72 hours.
      However, MELD-Na and MELD-XI were not predictive of 60-day clinical events.

PMID- 28433217
TI  - Clinical Significance of Prognostic Nutritional Index After Surgical Treatment in
      Lung Cancer.
AB  - BACKGROUND: The prognostic nutritional index (PNI), calculated as 10 * serum
      albumin (g/dL) + 0.005 * total lymphocyte count (cells/mm3), can reportedly
      predict postoperative complications and prognosis for various types of
      malignancy. However, the clinical significance and prognostic value of the PNI
      for both short- and long-term outcomes remains uncertain in patients with lung
      cancer. METHODS: We retrospectively reviewed 248 patients with completely
      resected non-small cell lung cancer (NSCLC). Clinicopathologic characteristics
      were evaluated according to the PNI, and the prognostic significance for
      postoperative outcomes was assessed using Cox proportional regression analysis.
      The survival rate was calculated using the Kaplan-Meier method. RESULTS: An
      optimal cutoff of 48 for recurrence-free survival (RFS) was determined using the
      minimum p value approach. Old age, low body mass index, large tumor size, and
      elevated C-reactive protein levels correlated significantly with low PNI.
      Logistic regression analysis demonstrated that low PNI status was statistically
      related to postoperative complications (Clavien-Dindo grade >=II) and pulmonary
      air leakage. Five-year overall survival (OR) rates in the high- and low-PNI
      groups were 80.6% and 58.5%, respectively (p = 0.002). Five-year RFS rates were
      73.6% and 48.6%, respectively (p < 0.001). Furthermore, PNI was identified as an
      independent prognostic factor for OS (hazard ratio [HR], 2.18; 95% confidence
      interval [CI], 1.08-4.21) and RFS (HR, 2.57; 95% CI, 1.46-4.38) by multivariate
      analysis. CONCLUSIONS: The PNI could represent a useful biomarker to predict
      postoperative complications and survival in patients with completely resected
      NSCLC.

PMID- 28433218
TI  - Cardiac Arrhythmia After Open Thoracoabdominal Aortic Aneurysm Repair.
AB  - BACKGROUND: Cardiac arrhythmias commonly arise after cardiac surgery and are
      associated with poor prognosis. In thoracoabdominal aortic aneurysm (TAAA)
      repair, these complications are poorly understood. We assessed characteristics,
      incidence, outcomes, and potential predictors of postoperative arrhythmia (PA)
      after open TAAA repair. METHODS: From 2010 to 2014, 403 consecutive open TAAA
      replacement operations were performed in patients without preoperative cardiac
      rhythm abnormalities at a single tertiary center. We compared preoperative
      characteristics, operative factors, and postoperative outcomes in patients with
      and without PA, and we used multivariable logistic regression to identify
      predictors of PA. RESULTS: PA occurred after 107 (26.5%) procedures. Atrial
      fibrillation (23%) was the most common type of PA. Length of hospital stay and
      operative mortality were greater in patients with PA than in patients without it
      (p < 0.01 for both). Kaplan-Meier cumulative survival for patients with PA was
      lower than for patients without PA: 69.2% +/- 4.6% versus 88.3% +/- 2.0% at 1
      year and 59.0% +/- 5.3% versus 85.0% +/- 2.3% at 3 years (p < 0.001 for both).
      The odds of PA increased with advancing age (1.07 per year; p < 0.001). In
      addition, the odds of developing PA were higher in patients who received visceral
      perfusion (odds ratio, 2.58; p = 0.001) and were lower in patients who underwent
      extent IV repair (odds ratio, 0.44; p = 0.01). CONCLUSIONS: Postoperative cardiac
      arrhythmia was common after open TAAA repair. Older patients and patients who
      underwent visceral perfusion were more likely to develop PA. Cardiac arrhythmia
      after TAAA repair was associated with prolonged hospital stay, higher early
      mortality, and lower midterm survival.

PMID- 28433219
TI  - Importance of Ground Glass Opacity Component in Clinical Stage IA Radiologic
      Invasive Lung Cancer.
AB  - BACKGROUND: We evaluated the clinical significance of the presence of a ground
      glass opacity (GGO) component in clinical stage IA radiologic invasive non-small
      cell lung cancer (NSCLC). METHODS: We reviewed 497 surgically resected clinical
      stage IA radiologic invasive NSCLCs, which were then classified into two groups
      based on consolidation tumor ratio (CTR), that is part-solid (0.5 <= CTR < 1.0, n
      = 177) and pure-solid (CTR = 1.0, n = 320). The part-solid tumors were subdivided
      into GGO-predominant (0.5 <= CTR < 0.75, n = 115) and solid-predominant (0.75 <=
      CTR < 1.0, n = 62) groups. Impact of tumor size was assessed based on CTR using
      Cox proportional hazards model. RESULTS: Among the radiologic invasive NSCLCs,
      multivariate analyses revealed that the presence of the carcinoembryonic antigen
      and a radiologic pure-solid appearance were independent significant prognostic
      variables (p = 0.019 and 0.034). The 5-year overall survival (OS) revealed
      significant differences between pure-solid and part-solid tumors (82.7% versus
      95.3%, p < 0.0001) and differed significantly among radiologic pure-solid NSCLCs
      in terms of maximum tumor size (<=20 mm: 86.1%, 21 to 30 mm: 78.1%, p = 0.0274).
      However, oncologic characteristics between GGO-predominant and solid-predominant
      types are clinicopathologically similar. The 5-year OS was equivalent in the GGO
      predominant and solid-predominant arms (5-year OS: 95.3% versus 96.8%, p =
      0.703). Furthermore, it was identical despite the maximum tumor size (<=20 mm:
      96.6%, 21 to 30 mm: 94.9%, p = 0.4810) or the solid component size (<=20 mm:
      96.0%, 21 to 30 mm: 93.8%, p = 0.6119). CONCLUSIONS: Presence of a GGO component
      might have a notable impact on a favorable prognosis even in clinical stage IA
      radiologic invasive NSCLCs. Therefore, a clear distinction between part-solid and
      pure-solid findings on thin-section computed tomography is extremely important
      when evaluating the oncologic outcomes of radiologically solid NSCLCs.

PMID- 28433220
TI  - Comparison of Two Minimally Invasive Techniques and Median Sternotomy in Aortic
      Valve Replacement.
AB  - BACKGROUND: Propensity score-matched analysis of the anterolateral
      minithoracotomy and the partial upper hemisternotomy vs the median sternotomy
      approach has not been reported to date for isolated aortic valve replacement.
      METHODS: From 2005 to 2013, isolated aortic valve replacement was performed
      through a partial upper hemisternotomy in 315 patients (38.9%), through a median
      sternotomy in 328 patients (40.5%), and through an anterolateral minithoracotomy
      in 167 patients (20.6%). After propensity score-matched analysis, both minimally
      invasive techniques were independently compared with median sternotomy in 118
      matched pairs. RESULTS: In the anterolateral group, conversion to median
      sternotomy was significantly higher (17 [14.4%]), a second pump run (6 [5.1%])
      and second cross clamp (12 [10.2%]) were significantly more often necessary, the
      median cross-clamp time (94 minutes; range, 43 to 231 minutes) and median
      perfusion time (141 minutes; range, 77 to 456 minutes) were significantly longer,
      and more groin complications occurred (17 [14.4%]), all compared with the median
      sternotomy group. No difference in perioperative results was identified between
      the partial upper hemisternotomy and the median sternotomy group. There was no
      significant difference in 1-year survival among the three groups, although a
      trend of better survival was observed in the partial upper hemisternotomy group.
      CONCLUSIONS: In minimally invasive isolated aortic valve replacement, the partial
      upper hemisternotomy shows similar perioperative outcome as the median
      sternotomy, whereas, the anterolateral minithoracotomy is associated with more
      perioperative complications. Therefore, only the partial upper hemisternotomy
      should be the preferred surgical technique for minimally invasive aortic valve
      replacement in the daily routine for a broad spectrum of surgeons.

PMID- 28433222
TI  - Long-Term Mortality Effect of Early Pacemaker Implantation After Surgical Aortic
      Valve Replacement.
AB  - BACKGROUND: The need for pacemaker implantation is a well-described complication
      of aortic valve replacement. Not so well described is the effect such an event
      has on long-term outcome. This study reviewed a 21-year experience at the Mayo
      Clinic (Rochester, Minnesota) with aortic valve replacement to understand the
      influence of early postoperative pacemaker implantation on long-term mortality
      rates more clearly. METHODS: This study retrospectively reviewed the records of
      5,842 patients without previous pacemaker implantation who underwent surgical
      aortic valve replacement from January 1993 through June 2014. The median age of
      these patients was 73 years (range, 65 to 79 years), the median ejection fraction
      was 62% (range, 53% to 68%), 3,853 patients were male (66%), and coronary artery
      bypass graft operation was performed in 2,553 (44%) of the patients studied.
      Early pacemaker implantation occurred in 146 patients (2.5%) within 30 days of
      surgical aortic valve replacement. RESULTS: The median follow-up of patients was
      11.1 years (range, 5.8 to 16.5 years), and all-cause mortality rates were 2.4% at
      30 days, 6.4% at 1 year, 23.1% at 5 years, 48.3% at 10 years, and 67.9% at 15
      years postoperatively. Early pacemaker implantation was associated with an
      increased risk of death after multivariable adjustment for baseline patients'
      characteristics (hazard ratio, 1.49; 95% confidence interval, 1.20, 1.84; p <
      0.001). CONCLUSIONS: Early pacemaker implantation as a complication of surgical
      aortic valve replacement is associated with an increased risk of long-term death.
      Valve replacement-related pacemaker implantation rates should be important
      considerations with respect to new valve replacement paradigms, especially in
      younger and lower-risk patients.

PMID- 28433221
TI  - C-Reactive Protein Predicts Acute Kidney Injury and Death After Coronary Artery
      Bypass Grafting.
AB  - BACKGROUND: A better prediction of postoperative acute kidney injury (AKI) is
      worthwhile in patients undergoing coronary artery bypass grafting (CABG) because
      AKI is associated with high rates of morbidity and mortality. The present study
      was performed to investigate whether preoperative C-reactive protein (CRP)
      predicted AKI and the long-term rate of mortality in CABG. METHODS: This
      retrospective cohort study included 1,656 patients whose high-sensitivity CRPs
      were measured before CABG at two tertiary referral centers from 2004 to 2010. The
      odds ratios and hazard ratios for AKI and all-cause mortality were measured
      according to the tertiles of CRP levels after the adjustment of multiple
      covariates. The net reclassification improvement and integrated discrimination
      improvement were calculated to determine whether the addition of CRP to the risk
      model improves predictive capacity. Patients were followed for 12 years. RESULTS:
      The prevalence of AKI was increased in the third tertile group (42.7%) compared
      with in the first tertile group (25.6%). The corresponding odds ratio of AKI and
      p values were 1.86 (95% confidence interval: 1.39 to 2.49) and <0.001,
      respectively. Compared with the existing risk model, the addition of CRP improved
      the predictability with 0.135 of net reclassification improvement (p = 0.005) and
      0.084 of integrated discrimination improvement (p < 0.001). There were 474 deaths
      (28.6%) during follow-up. The third tertile group exhibited a higher hazard ratio
      for mortality (1.63, 95% confidence interval: 1.27 to 2.08) than the first
      tertile group. This predictability for mortality remained consistent regardless
      of the presence of AKI. CONCLUSIONS: Preoperative CRP level is a predictor of
      postoperative AKI and mortality in patients undergoing CABG.

PMID- 28433223
TI  - Risk of Intraatrial Thrombi After Thoracoscopic Ablation in Absence of Heparin
      and Appendage Closure.
AB  - BACKGROUND: Catheter and surgical ablation of atrial fibrillation (AF) can be
      associated with a risk of thromboembolic events. The goal of this study was to
      assess optimal anticoagulation management during thoracoscopic ablation of AF.
      METHODS: Fifty-two patients with persistent or long-standing persistent AF
      underwent hybrid ablation consisting of thoracoscopic ablation followed by
      electrophysiologic (EP) evaluation and consecutive ablation if indicated. The
      thoracoscopic ablation was performed using three different anticoagulation
      protocols: (1) without periprocedural heparin and without occlusion of the left
      atrial appendage; (2) with periprocedural heparin but without left atrial
      appendage occlusion; and (3) with periprocedural heparin and left atrial
      appendage occlusion. Transesophageal echocardiography (TEE) was obligatorily used
      to screen for intraatrial thrombi before the surgical and EP procedure and before
      hospital discharge for patients in protocols 2 and 3. RESULTS: In group 1 (n =
      20), 1 patient (5%) had a postoperative stroke with persistent neurologic
      deficit, and 6 other patients (30%) had a new thrombus in the left atrial
      appendage seen on the pre-EP TEE. In group 2 (n = 6), 3 left atrial appendage
      thrombi occurred (50%; 2 on predischarge TEE and 1 on pre-EP TEE). In group 3 (n
      = 26), no intracardiac thrombi were found on predischarge and pre-EP TEE, and
      there were no strokes in this group of patients, namely, the rates of thrombus or
      stroke were significantly reduced when compared with groups 1 and 2 (p = 0.001).
      CONCLUSIONS: Thoracoscopic ablation of AF can be associated with a risk of left
      atrial appendage thrombus formation and possibly also stroke. With administration
      of heparin during the ablation, followed by occlusion of the left atrial
      appendage as a part of the procedure, this risk can be effectively reduced.

PMID- 28433224
TI  - The Importance of Age on Short-Term Outcomes Associated With Repair of Giant
      Paraesophageal Hernias.
AB  - BACKGROUND: Older patients have an increased incidence of paraesophageal hernia
      (PEH) and can be denied surgical assessment due to the perception of increased
      complications and mortality. This study examines the influence of age and
      comorbidities on early complications and other short-term outcomes of PEH repair.
      METHODS: From 2000 to 2016, data of surgically treated patients with PEH were
      prospectively recorded in an Institutional Review Board-approved database. Only
      patients whose hernia involved over 50% of the stomach were included. Patients
      were stratified by age (<70, 70 to 79, >=80 years of age) and compared in
      univariate and multivariate analyses. RESULTS: Overall, 524 patients underwent
      surgical PEH repair (<70: 261 [50%]; 70 to 79: 163 [31%]; >=80: 100 [19%]).
      Patients greater than or equal to 80 years of age had higher American Society of
      Anesthesiologists class, more comorbidities, larger hernias, and higher
      incidences of type IV PEH and acute presentation. Patients greater than or equal
      to 80 years of age had more postoperative complications, but not higher grade
      complications (Clavien-Dindo grade >=IIIa). Median length of stay was 1 day
      longer for patients greater than or equal to 80 years of age (5 days versus 4
      days for patients <70 and 70 to 79 years of age, respectively). Objective,
      radiologic hernia recurrence at 4.3 months postoperation was 17.3% and was not
      increased in the greater than or equal to 80 years of age group. After adjustment
      for comorbidities and other factors, age greater than or equal to 80 years was
      not a significant factor in predicting severe complications, readmission within
      30 days, or early recurrence. CONCLUSIONS: PEH repair is safe in physiologically
      stable patients, irrespective of age. Incidence of complications is higher in
      older patients, but complication severity and mortality are similar to those of
      younger patients. Patients with giant PEH should be given the opportunity to
      review treatments options with an experienced surgeon.

PMID- 28433226
TI  - A note from Editor's desk.

PMID- 28433225
TI  - Adjuvant Chemotherapy Is Associated With Improved Survival in Locally Invasive
      Node Negative Non-Small Cell Lung Cancer.
AB  - BACKGROUND: The objectives of this study are to explore factors that are
      associated with use of adjuvant chemotherapy and to evaluate its impact on
      overall survival in node-negative patients who undergo lung and chest wall
      resection for non-small cell lung cancer (NSCLC). METHODS: Patients who underwent
      concomitant lung and chest wall resection for NSCLC were abstracted from the
      National Cancer Database. Clinical, pathologic, treatment, and follow-up data
      were obtained. Patients with pathologic nodal metastases or patients who received
      any radiation treatment were excluded, and the cohort was dichotomized based on
      administration of adjuvant postoperative chemotherapy. RESULTS: Between 1998 and
      2010, 824 patients met the inclusion criteria. This cohort exclusively consisted
      of pT3 N0 patients who did not receive any induction treatment or adjuvant
      radiation treatment. Adjuvant chemotherapy was administered to 255 patients
      (31%). Patients in the chemotherapy group were younger and had shorter inpatient
      length of stay. Both groups had similar comorbidities, tumor size, unplanned
      readmission rate, and incomplete resection rate. In multivariable analysis,
      younger age and shorter length of stay were associated with a greater likelihood
      of receiving adjuvant chemotherapy. Adjuvant chemotherapy was associated with
      improved survival (hazard ratio 0.74, 95% CI: 0.6 to 0.9), whereas increasing
      age, white race, length of inpatient stay, tumor size, and residual tumor were
      independently associated with greater risk of death. CONCLUSIONS: Patients who
      undergo lobectomy with chest wall resection for locally advanced NSCLC should be
      strongly considered for postoperative adjuvant chemotherapy even in the absence
      of nodal disease. Actual selection of patients for adjuvant chemotherapy is
      affected by perioperative factors.

PMID- 28433228
TI  - [Arterial hypertension in the elderly].

PMID- 28433227
TI  - Nonsurgical Therapies for Basal Cell Carcinoma: A Review.
AB  - Basal cell carcinoma (BCC) is the most prevalent malignant tumor in humans and
      the local destruction of tissue that can result from excision has a significant
      impact on well-being. Treating BCC is costly for health care systems given the
      high incidence of this tumor, especially in older patients. Standard treatment
      involves either resection with histologic assessment of margins or Mohs
      micrographic surgery. Surgery is sometimes contraindicated, however, due to the
      presence of significant comorbidity or high cosmetic expectations. For such
      patients, nonsurgical treatments have become available. These alternatives can
      offer good local control of disease, preserve function, and achieve excellent
      cosmetic results.

PMID- 28433229
TI  - Splenectomy is associated with higher infection and pneumonia rates among trauma
      laparotomy patients.
AB  - Splenectomy increases lifetime risk of thromboembolism (VTE) and is associated
      with long-term infectious complications, primarily, overwhelming post-splenectomy
      infection (OPSI). Our objective was to evaluate risk of VTE and infection at
      index hospitalization post-splenectomy. Retrospective review of all patients who
      received a laparotomy in the NTDB. Propensity score matching for splenectomy was
      performed, based on ISS, abdominal abbreviated injury score >3, GCS, sex and
      mechanism. Major complications, VTE, and infection rates were compared. Multiple
      logistic regression models were utilized to evaluate splenectomy-associated
      complications. 93,221 laparotomies were performed and 17% underwent splenectomy.
      Multiple logistic regression models did not demonstrate an association between
      splenectomy and major complications (OR 0.96, 95% CI 0.91-1.03, p = 0.25) or VTE
      (OR 1.05, 95% CI 0.96-1.14, p = 0.33). Splenectomy was independently associated
      with infection (OR 1.07, 95% CI 1.00-1.14, p = 0.045). Subgroup analysis of
      patients with infection demonstrated that splenectomy was most strongly
      associated with pneumonia (OR 1.41, 95% CI 1.26-1.57, p < 0.001). Splenectomy is
      not associated with higher overall complication or VTE rates during index
      hospitalization. However, splenectomy is associated with a higher rate of
      pneumonia.

PMID- 28433230
TI  - North Pacific Surgical Association Presidential Address 2016 - Us, Them and You.
AB  - This is the Presidential Address from the 104th meeting of the North Pacific
      Surgical Association held in Tacoma, Washington November 8-9, 2016.

PMID- 28433231
TI  - Liver transplantation for acute liver failure.
AB  - Before liver transplantation became widely applicable as a treatment option, the
      mortality rate for acute liver failure was as high as 85%. Today, acute liver
      failure is a relatively common transplant indication in some settings, but the
      results of liver transplantation in this context appear to be worse than those
      for chronic forms of liver disease. In this review, we discuss the indications
      and contraindications for urgent liver transplantation. In particular, we
      consider the roles of auxiliary, ABO-incompatible, and urgent living donor liver
      transplantation and address the management of a "status 1" patient with total
      hepatectomy and portocaval shunt for toxic liver syndrome.

PMID- 28433232
TI  - Risk factors for psychiatric and behavioural adverse events associated with
      antiepileptic drugs in adolescents and children.

PMID- 28433233
TI  - Vagus nerve stimulation in children: A focus on intellectual disability.

PMID- 28433234
TI  - Response to "Sleep and executive functions in children with ADHD".

PMID- 28433235
TI  - [Stone free rate assesment after percutaneous nephrolithotomy using
      nephrolitometric nomogram].
AB  - BACKGROUND: Percutaneous nephrolithotomy remains the standard of care for kidney
      stones larger than 2cm. Therefore, setting a prognosis for complete stone
      resolution through this method is essential. The prognostic tools available have
      limited prediction. OBJECTIVES: To evaluate the stone-free rate in patients
      undergoing percutaneous nephrolithotomy with the Clinical Research Office of the
      Endourological Society nomogram and suggest modifications to improve the
      classification. MATERIAL AND METHODS: We analyzed a retrospective cohort of
      patients undergoing percutaneous nephrolithotomy applying the nephrolithometric
      nomogram specified. We modified the scale dividing the patients into 3groups: i
      from 80 to 110 points, II from 111 to 170 points, and III more than 170 points,
      respectively assessing the stone-free rate (Kruskall-Wallis test was performed,
      p<0.05). RESULTS: A total of 126 patients were included. According to the
      nehrolithometric nomogram the stone-free rate was 12.5% for patients with fewer
      than 111 points and 70.9% for those with 111 points or more. In the modification
      proposed for groups I, IIand III the stone-free rate was 12.5%, 50% and 80%
      respectively (p=0.000). CONCLUSIONS: Evaluation using the nephrolithometric
      nomogram demonstrated accurate stone-free rate prediction for complex and simple
      stones, with a lack of discrimination for patients with intermediate scores. Our
      modification enabled better differentiation of the intermediate groups from the
      high and low stone-free rate groups.

PMID- 28433236
TI  - Stretch for the treatment and prevention of contracture: an abridged
      republication of a Cochrane Systematic Review.
AB  - QUESTION: Is stretch effective for the treatment and prevention of contractures
      in people with neurological and non-neurological conditions? DESIGN: A Cochrane
      Systematic Review with meta-analyses of randomised trials. PARTICIPANTS: People
      with or at risk of contractures. INTERVENTION: Trials were considered for
      inclusion if they compared stretch to no stretch, or stretch plus co-intervention
      to co-intervention only. The stretch could be administered in any way. OUTCOME
      MEASURES: The outcome of interest was joint mobility. Two sets of meta-analyses
      were conducted with a random-effects model: one for people with neurological
      conditions and the other for people with non-neurological conditions. The quality
      of evidence supporting the results of the two sets of meta-analyses was assessed
      using GRADE. RESULTS: Eighteen studies involving 549 participants examined the
      effectiveness of stretch in people with neurological conditions, and provided
      useable data. The pooled mean difference was 2 deg (95% CI 0 to 3) favouring
      stretch. This was equivalent to a relative change of 2% (95% CI 0 to 3). Eighteen
      studies involving 865 participants examined the effectiveness of stretch in
      people with non-neurological conditions, and provided useable data. The pooled
      standardised mean difference was 0.2 SD (95% CI 0 to 0.3) favouring stretch. This
      translated to an absolute mean increase of 1 deg (95% CI 0 to 2) and a relative
      change of 1% (95% CI 0 to 2). The GRADE level of evidence was high for both sets
      of meta-analyses. CONCLUSION: Stretch does not have clinically important effects
      on joint mobility. [Harvey LA, Katalinic OM, Herbert RD, Moseley AM, Lannin NA,
      Schurr K (2017) Stretch for the treatment and prevention of contracture: an
      abridged republication of a Cochrane Systematic Review. Journal of Physiotherapy
      63: 67-75].

PMID- 28433237
TI  - Inspiratory muscle training improves respiratory muscle strength, functional
      capacity and quality of life in patients with chronic kidney disease: a
      systematic review.
AB  - QUESTION: Does inspiratory muscle training improve respiratory muscle strength,
      functional capacity, lung function and quality of life of patients with chronic
      kidney disease? Does inspiratory muscle training improve these outcomes more than
      breathing exercises? DESIGN: Systematic review and meta-analysis of randomised
      trials. PARTICIPANTS: People with chronic kidney disease undergoing dialysis
      treatment. OUTCOME MEASURES: The primary outcomes were: maximal inspiratory
      pressure, maximal expiratory pressure, and distance covered on the 6-minute walk
      test. The secondary outcomes were: forced vital capacity, forced expiratory
      volume in the first second (FEV1), and quality of life. RESULTS: The search
      identified four eligible studies. The sample consisted of 110 participants. The
      inspiratory muscle training used a Threshold(r) or PowerBreathe(r) device, with a
      load ranging from 30 to 60% of the maximal inspiratory pressure and lasting from
      6 weeks to 6 months. The studies showed moderate to high risk of bias, and the
      quality of the evidence was rated low or very low, due to the studies'
      methodological limitations. The meta-analysis showed that inspiratory muscle
      training significantly improved maximal inspiratory pressure (MD 23 cmH2O, 95% CI
      16 to 29) and the 6-minute walk test distance (MD 80m, 95% CI 41 to 119) when
      compared with controls. Significant benefits in lung function and quality of life
      were also identified. When compared to breathing exercises, significant benefits
      were identified in maximal expiratory pressure (MD 6 cmH2O, 95% CI 2 to 10) and
      FEV1 (MD 0.24litres 95% CI 0.14 to 0.34), but not maximal inspiratory pressure or
      forced vital capacity. CONCLUSION: In patients with chronic renal failure on
      dialysis, inspiratory muscle training with a fixed load significantly improves
      respiratory muscle strength, functional capacity, lung function and quality of
      life. The evidence for these benefits may be influenced by some sources of bias.
      REGISTRATION: PROSPERO (CRD 42015029986). [de Medeiros AIC, Fuzari HKB, Rattesa
      C, Brandao DC, de Melo Marinho PE (2017) Inspiratory muscle training improves
      respiratory muscle strength, functional capacity and quality of life in patients
      with chronic kidney disease: a systematic review. Journal of Physiotherapy 63: 76
      83].

PMID- 28433238
TI  - Pulmonary rehabilitation referral and participation are commonly influenced by
      environment, knowledge, and beliefs about consequences: a systematic review using
      the Theoretical Domains Framework.
AB  - QUESTION: What are the barriers and enablers of referral, uptake, attendance and
      completion of pulmonary rehabilitation for people with chronic obstructive
      pulmonary disease (COPD)? DESIGN: Systematic review of qualitative or
      quantitative studies reporting data relating to referral, uptake, attendance
      and/or completion in pulmonary rehabilitation. PARTICIPANTS: People aged >18years
      with a diagnosis of COPD and/or their healthcare professionals. DATA EXTRACTION
      AND ANALYSIS: Data were extracted regarding the nature of barriers and enablers
      of pulmonary rehabilitation referral and participation. Extracted data items were
      mapped to the Theoretical Domains Framework (TDF). RESULTS: A total of 6969
      references were screened, with 48 studies included and 369 relevant items mapped
      to the TDF. The most frequently represented domain was 'Environment' (33/48
      included studies, 37% of mapped items), which included items such as waiting
      time, burden of illness, travel, transport and health system resources. Other
      frequently represented domains were 'Knowledge' (18/48 studies, including items
      such as clinician knowledge of referral processes, patient understanding of
      rehabilitation content) and 'Beliefs about consequences' (15/48 studies,
      including items such as beliefs regarding role and safety of exercise,
      expectations of rehabilitation outcomes). Barriers to referral, uptake,
      attendance or completion represented 71% (n=183) of items mapped to the TDF. All
      domains of the TDF were represented; however, items were least frequently coded
      to the domains of 'Optimism' and 'Memory'. The methodological quality of included
      studies was fair (mean quality score 9/12, SD 2). CONCLUSION: Many factors -
      particularly those related to environment, knowledge, attitudes and behaviours -
      interact to influence referral, uptake, attendance and completion of pulmonary
      rehabilitation. Overcoming the challenges associated with the personal and/or
      healthcare system environment will be imperative to improving access and uptake
      of pulmonary rehabilitation. TRIAL REGISTRATION: PROSPERO CRD42015015976. [Cox
      NS, Oliveira CC, Lahham A, Holland AE (2017) Pulmonary rehabilitation referral
      and participation are commonly influenced by environment, knowledge, and beliefs
      about consequences: a systematic review using the Theoretical Domains Framework.
      Journal of Physiotherapy 63: 84-93].

PMID- 28433240
TI  - An elicitation study of critical care nurses' salient hand hygiene beliefs.
AB  - AIM: To describe critical care nurses' hand hygiene attitudinal, normative
      referent, and control beliefs. BACKGROUND: Hand hygiene is the primary strategy
      to prevent healthcare-associated infections. Social influence is an
      underdeveloped hand hygiene strategy. METHODS: This qualitative descriptive study
      was conducted with 25 ICU nurses in the southeastern United States. Data were
      collected using the Nurses' Salient Belief Instrument. RESULTS: Thematic analysis
      generated four themes: Hand Hygiene is Protective; Nurses look to Nurses; Time
      related Concerns; and Convenience is Essential. CONCLUSION: Nurses look to nurses
      as hand hygiene referents and believe hand hygiene is a protective behaviour that
      requires time and functional equipment.

PMID- 28433239
TI  - Shame feeling in the Intensive Care Unit patient's family members.
AB  - OBJECTIVE: To investigate the levels of internal and external shame among family
      members of critically ill patients. RESEARCH METHODOLOGY/ DESIGN: This
      prospective study was conducted in 2012/2013 on family members of Intensive Care
      Unit patients using the Others As Shamer Scale and the Experiential Shame Scale
      questionnaires. SETTING: Greek university hospital. RESULTS: Two hundred and
      twenty-three family members mean-aged (41.5+/-11.9) were studied, corresponding
      to 147 ICU patients. Out of these 223, 81 (36.3%) were men and 142 (63.7%) were
      women, while 79 (35.4%) lived with the patient. Family members who lived with the
      patient experienced higher internal and external shame compared to those who did
      not live with the patient (p=0.046 and p=0.028 respectively). Elementary and
      Junior High School graduates scored significantly higher than the other grades
      graduates in total Others As Shamer Scale, inferiority and emptiness scale
      (p<0.001). CONCLUSION: Intensive Care Unit patients' family members are prone to
      shame feelings, especially when being of low educational level. Health
      professionals have to take into consideration the possible implications for the
      patients and their care.

PMID- 28433241
TI  - Mechanics of additively manufactured biomaterials.
AB  - Additive manufacturing (3D printing) has found many applications in healthcare
      including fabrication of biomaterials as well as bioprinting of tissues and
      organs. Additively manufactured (AM) biomaterials may possess arbitrarily complex
      micro-architectures that give rise to novel mechanical, physical, and biological
      properties. The mechanical behavior of such porous biomaterials including their
      quasi-static mechanical properties and fatigue resistance is not yet well
      understood. It is particularly important to understand the relationship between
      the designed micro-architecture (topology) and the resulting mechanical
      properties. The current special issue is dedicated to understanding the
      mechanical behavior of AM biomaterials. Although various types of AM biomaterials
      are represented in the special issue, the primary focus is on AM porous metallic
      biomaterials. As a prelude to this special issue, this editorial reviews some of
      the latest findings in the mechanical behavior of AM porous metallic biomaterials
      so as to describe the current state-of-the-art and set the stage for the other
      studies appearing in the issue. Some areas that are important for future research
      are also briefly mentioned.

PMID- 28433242
TI  - Freeform extrusion fabrication of titanium fiber reinforced 13-93 bioactive glass
      scaffolds.
AB  - Although implants made with bioactive glass have shown promising results for bone
      repair, their application in repairing load-bearing long bone is limited due to
      their poor mechanical properties in comparison to human bone. This work
      investigates the freeform extrusion fabrication of bioactive silicate 13-93 glass
      scaffolds reinforced with titanium (Ti) fibers. A composite paste prepared with
      13-93 glass and Ti fibers (~16um in diameter and lengths varying from ~200um to
      ~2 mm) was extruded through a nozzle to fabricate scaffolds (0-90 degrees 
      filament orientation pattern) on a heated plate. The sintered scaffolds measured
      pore sizes ranging from 400 to 800um and a porosity of ~50%. Scaffolds with
      0.4vol% Ti fibers measured fracture toughness of ~0.8MPam1/2 and a flexural
      strength of ~15MPa. 13-93 glass scaffolds without Ti fibers had a toughness of
      ~0.5MPam1/2 and a strength of ~10MPa. The addition of Ti fibers increased the
      fracture toughness of the scaffolds by ~70% and flexural strength by ~40%. The
      scaffolds' biocompatibility and their degradation in mechanical properties in
      vitro were assessed by immersing the scaffolds in a simulated body fluid over a
      period of one to four weeks.

PMID- 28433243
TI  - CoCr F75 scaffolds produced by additive manufacturing: Influence of chemical
      etching on powder removal and mechanical performance.
AB  - Additive manufacturing techniques such as Selective Laser Melting (SLM) allow
      carefully controlled production of complex porous structures such as scaffolds.
      These advanced structures can offer many interesting advantages over
      conventionally produced products in terms of biological response and patient
      specific design. The surface finish of AM parts is often poor because of the
      layer wise nature of the process and adhering particles. Loosening of these
      particles after implantation should be avoided, as this could put the patient's
      health at risk. In this study the use of hydrochloric acid and hydrogen peroxide
      mixtures for surface treatment of cobalt-chromium F75 scaffolds produced by SLM
      is investigated. A 27% HCl and 8% H2O2 etchant proved effective in removing
      adhering particles while retaining the quasi-static and fatigue performance of
      the scaffolds.

PMID- 28433244
TI  - Reliability in cerebellar size assessment by 2D cranial ultrasonography in
      neonates.
AB  - BACKGROUND: Cerebellar size appears to be correlated with the long-term outcome
      of preterm infants. Two-dimensional cranial ultrasonography (2D-cUS) is the first
      line, routine tool to characterize newborn cerebral structures. Information
      regarding the accuracy of 2D-cUS for assessing cerebellar size is scarce.
      OBJECTIVES: To assess the reliability of cerebellar size using 2D-cUS. METHODS:
      Fifty infants were prospectively scanned for a variety of clinical indications.
      The scans were stored and then independently analyzed offline by two observers.
      The transverse cerebellar diameter coronally from the anterior and mastoid
      fontanels (TCD-AF and TCD-MF, respectively); the midsagittal cerebellar vermis
      height and the anterior-posterior diameter from the AF; and the width and height
      of the fourth ventricle coronally from the MF view were measured. Interobserver
      variability was assessed using the intraclass correlation (ICC) with 95%
      confidence interval (CI) for each of the paired measures. RESULTS: A total 294
      images were included in the analysis. The interobserver ICCs were TCD-AF = 0.85
      (0.76-0.91), TCD-MF = 0.9 (0.83-0.94), vermis height = 0.79 (0.66-0.88), anterior
      posterior vermis diameter = 0.71 (0.5-0.84), width of the fourth ventricle = 0.72
      (0.33-0.9), height of the fourth ventricle = 0.86 (0.7-0.92). The ICC for the TCD
      comparing the AF and the MF approach was >=0.9 for both observers. CONCLUSIONS:
      The reliability of the offline 2D-cUS cerebellar size assessments is good, and
      TCD-MF is the most consistent measure. Further studies should address the
      predictive value for the neurodevelopmental outcome of serial cerebellar size
      assessments by 2D-cUS for preterm infants.

PMID- 28433245
TI  - Council happenings.

PMID- 28433246
TI  - What nurses are fighting for: The elevator briefing.

PMID- 28433247
TI  - Outpatient Laparoscopic Appendectomy: Feasible in a Public County Hospital?
AB  - BACKGROUND: Outpatient laparoscopic appendectomy is being used increasingly as a
      treatment option for acute, uncomplicated appendicitis. This was a prospective
      validation study in a large, urban, public safety-net hospital. STUDY DESIGN:
      From 2014 to 2016, all patients undergoing laparoscopic appendectomy for acute,
      uncomplicated appendicitis were enrolled in a prospective observational trial.
      Standard baseline perioperative practice (control group) was documented for 1
      year. An outpatient appendectomy protocol was then introduced. Inclusion criteria
      required intraoperative confirmation of uncomplicated appendicitis and strict
      discharge criteria, including physician assessment before discharge. Data
      collection then continued for 1 year (outpatient group). The outcomes measures
      examined included complications, length of stay, nursing transitions, emergency
      department visits, readmissions, and patient satisfaction. RESULTS: The study
      enrolled 351 patients (178 control, 173 outpatient). Of the 173 candidates for
      outpatient appendectomy, 113 went home. Reasons for admission included surgeon
      discretion due to intraoperative findings/medical comorbidities and lack of
      transportation home. The outpatient group had shorter operative time (69 vs 83
      minutes; p < 0.001), longer time in recovery (242 vs 141 minutes; p < 0.001),
      fewer nursing transitions (4 vs 5; p < 0.001), and shorter postoperative length
      of stay (9 vs 19 hours; p < 0.001). There was no difference in complications,
      emergency department visits, or readmissions. In the outpatient group, none of
      the patients sent home from recovery had postoperative complications or required
      readmission. Satisfaction surveys revealed no change in satisfaction with either
      protocol. CONCLUSIONS: Outpatient appendectomy is safe in a public hospital and
      results in shorter hospital length of stay and decreased healthcare costs. Strict
      criteria for discharge are important to identify patients who should be admitted
      for observation.

PMID- 28433248
TI  - There is no evidence that Podoctidae carry eggs of their own species: Reply to
      Machado and Wolff (2017).
AB  - In our recent publication (Sharma et al., 2017), we tested the hypothesis that
      eggs attached to the legs of male Podoctidae (Opiliones, Laniatores) constituted
      a case of paternal care, using molecular sequence data in tandem with multiple
      sequence alignments to test the prediction that sequences of the eggs and the
      adults that carried them would indicate conspecific identity. We discovered that
      the sequences of the eggs belonged to spiders, and thus rejected the paternal
      care hypothesis for these species. Machado and Wolff (2017) recently critiqued
      our work, which they regarded as a non-critical interpretation and over-reliance
      on molecular sequence data, and defended the traditional argument that the eggs
      attached to podoctids are in fact harvestman eggs. Here we show that additional
      molecular sequence data also refute the identity of the eggs as conspecific
      harvestman eggs, using molecular cloning techniques to rule out contamination. We
      show that individual gene trees consistently and reliably place the egg and adult
      sequences in disparate parts of the tree topology. Phylogenetic methods
      consistently place all egg sequences within the order Araneae (spiders). We
      submit that evidence for the paternal care hypothesis based on behavioral,
      morphological, and natural history approaches is either absent or insufficient
      for concluding that the eggs of podoctids are conspecific.

PMID- 28433249
TI  - Multicenter analysis of impact of anastomotic leakage on long-term oncologic
      outcomes after curative resection of colon cancer.
AB  - BACKGROUND: In rectal cancer, anastomotic leakage was reported to have a negative
      impact on both short- and long-term outcomes. However, there is limited data on
      the impact of anastomotic leakage on oncologic outcomes in patients with colon
      cancer. We aimed to evaluate the impact of anastomotic leakage on disease
      recurrence and long-term survival after curative resection of colon cancer.
      METHODS: This multicenter, retrospective cohort study of 4,919 consecutive
      patients utilized data from the Japanese Society for Cancer of the Colon and
      Rectum. Multivariable Cox regression analysis was used to adjust for confounding.
      RESULTS: The incidence of anastomotic leakage was 2.5% and 30-day mortality was
      0.21%. The 5-year overall survival rate was 80.8% in the anastomotic leakage
      group, compared with 90.3% in the no leak group (P = .001). In the multivariable
      analysis, anastomotic leakage was significantly associated with reduced overall
      survival rate (hazard ratio = 1.84; 95% confidence interval, 1.06-2.96). Overall
      disease recurrence rate was 14.1%: 21.2% in the anastomotic leakage group and
      13.9% in the no leak group. There was a significant association between
      anastomotic leakage and local recurrence (hazard ratio = 4.63; 95% confidence
      interval, 1.60-10.6). In contrast, anastomotic leakage was not significantly
      associated with total distant recurrence. However, anastomotic leakage did show a
      tendency toward increasing peritoneal recurrence, although it did not reach
      statistical significance (hazard ratio = 2.59; 95% confidence interval, 0.79
      6.29). CONCLUSION: In our study population, anastomotic leakage was associated
      with reduced overall survival and with increased rate of local recurrence after
      curative resection for colon cancer.

PMID- 28433250
TI  - Public-private implementation of integrated emergency response services: Case
      study of GVK Emergency Management and Research Institute in Karnataka, India.
AB  - BACKGROUND: Emergency medical services are important to the functioning of health
      systems, but these services tend to be neglected in low- and middle-income
      countries, such as India. In recent years, several models of pre-hospital
      emergency medical services have emerged in India. Research on these models holds
      important lessons for existing and future emergency medical service programs in
      low- and middle-income countries. Our objective was to provide a comprehensive
      description of the organizational structure and service delivery model of a
      public-private partnership in the southern Indian state of Karnataka, GVK
      Emergency Management and Research Institute, with a particular focus on its
      operations in Bengaluru. METHODS: A case study methodology was used to explore
      systematically the organizational model of GVK Emergency Management and Research
      Institute in Karnataka. Qualitative data were collected through an in-person site
      visit to GVK Emergency Management and Research Institute headquarters in
      Bengaluru in July 2013. Three sources were used: in-depth, semistructured
      interviews, document review, and nonparticipant observation. Data were analyzed
      according to the health system "building blocks" proposed by the World Health
      Organization. RESULTS: The organization follows a standardized model across the
      states and union territories where they have contractual arrangements, including
      Karnataka. Processes for fleet maintenance, information systems/information
      technology and training, and deployment were well structured at the
      organizational level. The public-private partnership appears pro-poor in
      orientation; however, further demand-side research is required on the perspective
      of patients. CONCLUSION: Our study reveals a functional structure at the
      organizational level, which provides a key service at no cost to users. Detailed
      analyses of this nature can help inform global efforts for the development and
      strengthening of emergency medical services systems.

PMID- 28433251
TI  - Erratum to "Exploring links between language and cognition in autism spectrum
      disorders: Complement sentences, false belief, and executive functioning" [J.
      Commun. Disord. 54 (2015) 15-31].

PMID- 28433252
TI  - NRASQ61R immunohistochemistry detects both NRASQ61R and KRASQ61R mutations in
      colorectal cancer.
AB  - The NRASQ61R monoclonal antibody (clone sp174) is a mutation-specific antibody
      that is increasingly being used to detect the NRASQ61R mutation in melanomas.
      This antibody has been reported to be highly correlated with the NRASQ61R
      mutation status in melanomas and follicular neoplasms of the thyroid gland.
      However, its utility in colorectal carcinoma (CRC) has remained largely unknown.
      In this study, we assessed the sensitivity, specificity, and diagnostic utility
      of NRASQ61R immunohistochemistry in a cohort consisting of tissue sections of 113
      CRCs, which were molecularly profiled for the KRAS, NRAS, and BRAF mutations.
      Five CRCs tested positive for NRASQ61R immunohistochemistry. Four of these CRCs
      exhibited the NRASQ61R mutation and one exhibited the KRASQ61R mutation. All of
      the other 108 colorectal carcinomas lacking the NRASQ61R or KRASQ61R mutation
      tested negative for NRASQ61R immunohistochemistry. In the positively stained
      cases, we observed a diffuse staining pattern in >90% of the tumour cells with a
      moderate-to-strong intensity. By contrast, the staining was essentially entirely
      negative in cases negative for the NRASQ61R or KRASQ61R mutations. We concluded
      that although it cross-reacts with the mutant KRASQ61R protein, the NRASQ61R
      antibody is a useful diagnostic tool that assists in the molecular testing of
      CRCs and facilitates patient management.

PMID- 28433253
TI  - Neuropeptide S increases motor activity and thermogenesis in the rat through
      sympathetic activation.
AB  - The central role of neuropeptide S (NPS), identified as the endogenous ligand for
      GPR154, now named neuropeptide S receptor (NPSR), has not yet been fully
      clarified. We examined the central role of NPS for body temperature, energy
      expenditure, locomotor activity and adrenal hormone secretion in rats.
      Intracerebroventricular (icv) injection of NPS increased body temperature in a
      dose-dependent manner. Energy consumption and locomotor activity were also
      significantly increased by icv injection of NPS. In addition, icv injection of
      NPS increased the peripheral blood concentration of adrenalin and corticosterone.
      Pretreatment with the beta1- and beta2-adrenergic receptor blocker timolol
      inhibited the NPS-induced increase of body temperature. The expression of both
      NPS mRNA in the brainstem and NPSR mRNA in the hypothalamus showed a nocturnal
      rhythm with a peak occurring during the first half of the dark period. To examine
      whether the endogenous NPS is involved in regulation of body temperature, NPSR
      antagonist SHA68 was administered one hour after darkness. SHA68 attenuated the
      nocturnal rise of body temperature. These results suggest that NPS contributes to
      the regulation of the sympathetic nervous system.

PMID- 28433254
TI  - Does adjuvant therapy improve overall survival for stage IA/B pancreatic
      adenocarcinoma?
AB  - BACKGROUND: Current guidelines recommend adjuvant chemotherapy for resected
      pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival
      benefit for stage I patients as they comprise <10% of PDAC. METHODS: Using the
      NCDB 2006-2012, resected PDAC patients with stage I disease who received adjuvant
      therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with
      overall survival (OS) were identified. RESULTS: 3909 patients with resected stage
      IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and
      36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant
      chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant
      chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and
      <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age >=70 (p <
      0.001), higher grade (p < 0.001), <=10 lymph nodes examined (p = 0.008), positive
      margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were
      associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar
      associations were observed with the exception of adjuvant chemoradiation whereby
      there was no significant association (p = 0.35). CONCLUSION: Adjuvant
      chemotherapy was associated with an OS benefit for patients with stage I PDAC;
      adjuvant chemoradiation was either of no benefit or associated with worse OS.

PMID- 28433255
TI  - Digital Cohorts Within the Social Mediome: An Approach to Circumvent Conventional
      Research Challenges?

PMID- 28433257
TI  - Patterns of global health financing and potential future spending on health.

PMID- 28433258
TI  - Securing investments to realise the social and economic rights of adolescents.

PMID- 28433256
TI  - Evolution and patterns of global health financing 1995-2014: development
      assistance for health, and government, prepaid private, and out-of-pocket health
      spending in 184 countries.
AB  - BACKGROUND: An adequate amount of prepaid resources for health is important to
      ensure access to health services and for the pursuit of universal health
      coverage. Previous studies on global health financing have described the
      relationship between economic development and health financing. In this study, we
      further explore global health financing trends and examine how the sources of
      funds used, types of services purchased, and development assistance for health
      disbursed change with economic development. We also identify countries that
      deviate from the trends. METHODS: We estimated national health spending by type
      of care and by source, including development assistance for health, based on a
      diverse set of data including programme reports, budget data, national estimates,
      and 964 National Health Accounts. These data represent health spending for 184
      countries from 1995 through 2014. We converted these data into a common inflation
      adjusted and purchasing power-adjusted currency, and used non-linear regression
      methods to model the relationship between health financing, time, and economic
      development. FINDINGS: Between 1995 and 2014, economic development was positively
      associated with total health spending and a shift away from a reliance on
      development assistance and out-of-pocket (OOP) towards government spending. The
      largest absolute increase in spending was in high-income countries, which
      increased to purchasing power-adjusted $5221 per capita based on an annual growth
      rate of 3.0%. The largest health spending growth rates were in upper-middle
      income (5.9) and lower-middle-income groups (5.0), which both increased spending
      at more than 5% per year, and spent $914 and $267 per capita in 2014,
      respectively. Spending in low-income countries grew nearly as fast, at 4.6%, and
      health spending increased from $51 to $120 per capita. In 2014, 59.2% of all
      health spending was financed by the government, although in low-income and lower
      middle-income countries, 29.1% and 58.0% of spending was OOP spending and 35.7%
      and 3.0% of spending was development assistance. Recent growth in development
      assistance for health has been tepid; between 2010 and 2016, it grew annually at
      1.8%, and reached US$37.6 billion in 2016. Nonetheless, there is a great deal of
      variation revolving around these averages. 29 countries spend at least 50% more
      than expected per capita, based on their level of economic development alone,
      whereas 11 countries spend less than 50% their expected amount. INTERPRETATION:
      Health spending remains disparate, with low-income and lower-middle-income
      countries increasing spending in absolute terms the least, and relying heavily on
      OOP spending and development assistance. Moreover, tremendous variation shows
      that neither time nor economic development guarantee adequate prepaid health
      resources, which are vital for the pursuit of universal health coverage. FUNDING:
      The Bill & Melinda Gates Foundation.

PMID- 28433259
TI  - Building the foundations for sustainable development: a case for global
      investment in the capabilities of adolescents.
AB  - Investment in the capabilities of the world's 1.2 billion adolescents is vital to
      the UN's Sustainable Development Agenda. We examined investments in countries of
      low income, lower-middle income, and upper-middle income covering the majority of
      these adolescents globally to derive estimates of investment returns given
      existing knowledge. The costs and effects of the interventions were estimated by
      adapting existing models and by extending methods to create new modelling tools.
      Benefits were valued in terms of increased gross domestic product and averted
      social costs. The initial analysis showed high returns for the modelled
      interventions, with substantial variation between countries and with returns
      generally higher in low-income countries than in countries of lower-middle and
      upper-middle income. For interventions targeting physical, mental, and sexual
      health (including a human papilloma virus programme), an investment of US$4.6 per
      capita each year from 2015 to 2030 had an unweighted mean benefit to cost ratio
      (BCR) of more than 10.0, whereas, for interventions targeting road traffic
      injuries, a BCR of 5.9 (95% CI 5.8-6.0) was achieved on investment of $0.6 per
      capita each year. Interventions to reduce child marriage ($3.8 per capita each
      year) had a mean BCR of 5.7 (95% CI 5.3-6.1), with the effect high in low-income
      countries. Investment to increase the extent and quality of secondary schooling
      is vital but will be more expensive than other interventions-investment of $22.6
      per capita each year from 2015 to 2030 generated a mean BCR of 11.8 (95% CI 11.6
      12.0). Investments in health and education will not only transform the lives of
      adolescents in resource-poor settings, but will also generate high economic and
      social returns. These returns were robust to substantial variation in
      assumptions. Although the knowledge base on the impacts of interventions is
      limited in many areas, and a major research effort is needed to build a more
      complete investment framework, these analyses suggest that comprehensive
      investments in adolescent health and wellbeing should be given high priority in
      national and international policy.

PMID- 28433261
TI  - Dyspnea in Children: What is driving it and how to approach it.
AB  - Dyspnea in children has important physical and psychosocial impact. It is useful
      to define the quality of the dyspnea and quantify its magnitude in a child
      friendly manner. Through careful history taking and physical examination, a
      targeted investigation can lead to identification of the cause and potential
      treatment. This article provides a framework for the clinical approach to dyspnea
      in children, including important information to gather during the history,
      physical assessment, how to quantify dyspnea, and choice and use of laboratory
      measurements.

PMID- 28433262
TI  - Primary motor cortex alterations in Alzheimer disease: A study in the 3xTg-AD
      model.
AB  - INTRODUCTION: In humans and animal models, Alzheimer disease (AD) is
      characterised by accumulation of amyloid-beta peptide (Abeta) and
      hyperphosphorylated tau protein, neuronal degeneration, and astrocytic gliosis,
      especially in vulnerable brain regions (hippocampus and cortex). These
      alterations are associated with cognitive impairment (loss of memory) and non
      cognitive impairment (motor impairment). The purpose of this study was to
      identify cell changes (neurons and glial cells) and aggregation of Abeta and
      hyperphosphorylated tau protein in the primary motor cortex (M1) in 3xTg-AD mouse
      models at an intermediate stage of AD. METHODS: We used female 3xTg-AD mice aged
      11 months and compared them to non-transgenic mice of the same age. In both
      groups, we assessed motor performance (open field test) and neuronal damage in M1
      using specific markers: BAM10 (extracellular Abeta aggregates), tau 499
      (hyperphosphorylated tau protein), GFAP (astrocytes), and Kluver-Barrera staining
      (neurons). RESULTS: Female 3xTg-AD mice in intermediate stages of the disease
      displayed motor and cellular alterations associated with Abeta and
      hyperphosphorylated tau protein deposition in M1. CONCLUSIONS: Patients with AD
      display signs and symptoms of functional impairment from early stages. According
      to our results, M1 cell damage in intermediate-stage AD affects motor function,
      which is linked to progression of the disease.

PMID- 28433263
TI  - Memory assessment in patients with temporal lobe epilepsy to predict memory
      impairment after surgery: A systematic review.
AB  - INTRODUCTION: Given that surgical treatment of refractory mesial temporal lobe
      epilepsy may cause memory impairment, determining which patients are eligible for
      surgery is essential. However, there is little agreement on which presurgical
      memory assessment methods are best able to predict memory outcome after surgery
      and identify those patients with a greater risk of surgery-induced memory
      decline. OBJECTIVE: We conducted a systematic literature review to determine
      which presurgical memory assessment methods best predict memory outcome. MATERIAL
      AND METHODS: The literature search of PubMed gathered articles published between
      January 2005 and December 2015 addressing pre- and postsurgical memory assessment
      in mesial temporal lobe epilepsy patients by means of neuropsychological testing,
      functional MRI, and other neuroimaging techniques. We obtained 178 articles, 31
      of which were included in our review. RESULTS: Most of the studies used
      neuropsychological tests and fMRI; these methods are considered to have the
      greatest predictive ability for memory impairment. Other less frequently used
      techniques included the Wada test and FDG-PET. CONCLUSIONS: Current evidence
      supports performing a presurgical assessment of memory function using both
      neuropsychological tests and functional MRI to predict memory outcome after
      surgery.

PMID- 28433264
TI  - Practical Tips for Insulin Use in Primary Care.

PMID- 28433260
TI  - Future and potential spending on health 2015-40: development assistance for
      health, and government, prepaid private, and out-of-pocket health spending in 184
      countries.
AB  - BACKGROUND: The amount of resources, particularly prepaid resources, available
      for health can affect access to health care and health outcomes. Although health
      spending tends to increase with economic development, tremendous variation exists
      among health financing systems. Estimates of future spending can be beneficial
      for policy makers and planners, and can identify financing gaps. In this study,
      we estimate future gross domestic product (GDP), all-sector government spending,
      and health spending disaggregated by source, and we compare expected future
      spending to potential future spending. METHODS: We extracted GDP, government
      spending in 184 countries from 1980-2015, and health spend data from 1995-2014.
      We used a series of ensemble models to estimate future GDP, all-sector government
      spending, development assistance for health, and government, out-of-pocket, and
      prepaid private health spending through 2040. We used frontier analyses to
      identify patterns exhibited by the countries that dedicate the most funding to
      health, and used these frontiers to estimate potential health spending for each
      low-income or middle-income country. All estimates are inflation and purchasing
      power adjusted. FINDINGS: We estimated that global spending on health will
      increase from US$9.21 trillion in 2014 to $24.24 trillion (uncertainty interval
      [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase
      fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This
      growth is driven by continued growth in GDP, government spending, and government
      health spending. Lower-middle income countries are expected to grow at 4.2% (3.8
      4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low
      income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth,
      health spending per capita in low-income countries is expected to remain low, at
      $154 (UI 133-181) per capita in 2030 and $195 (157-258) per capita in 2040.
      Increases in national health spending to reach the level of the countries who
      spend the most on health, relative to their level of economic development, would
      mean $321 (157-258) per capita was available for health in 2040 in low-income
      countries. INTERPRETATION: Health spending is associated with economic
      development but past trends and relationships suggest that spending will remain
      variable, and low in some low-resource settings. Policy change could lead to
      increased health spending, although for the poorest countries external support
      might remain essential. FUNDING: Bill & Melinda Gates Foundation.

PMID- 28433265
TI  - High-pressure microscopy for tracking dynamic properties of molecular machines.
AB  - High-pressure microscopy is one of the powerful techniques to visualize the
      effects of hydrostatic pressures on research targets. It could be used for
      monitoring the pressure-induced changes in the structure and function of
      molecular machines in vitro and in vivo. This review focuses on the dynamic
      properties of the assemblies and machines, analyzed by means of high-pressure
      microscopy measurement. We developed a high-pressure microscope that is optimized
      both for the best image formation and for the stability to hydrostatic pressure
      up to 150 MPa. Application of pressure could change polymerization and
      depolymerization processes of the microtubule cytoskeleton, suggesting a
      modulation of the intermolecular interaction between tubulin molecules. A novel
      motility assay demonstrated that high hydrostatic pressure induces
      counterclockwise (CCW) to clockwise (CW) reversals of the Escherichia coli
      flagellar motor. The present techniques could be extended to study how molecular
      machines in complicated systems respond to mechanical stimuli.

PMID- 28433266
TI  - Mike Begon: Winning Public Arguments As Ecologists: Time for a New Doctrine?

PMID- 28433267
TI  - Dose-response effects of supplementation with calcifediol on serum 25
      hydroxyvitamin D status and its metabolites: A randomized controlled trial in
      older adults.
AB  - BACKGROUND & AIMS: Oral supplementation with vitamin D is recommended for older
      adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout
      the year. While supplementation with vitamin D2 or D3 is most common, alternative
      treatment regimens exist which require further investigation with respect to
      increasing 25(OH)D concentration. We investigated the dose-response effects of
      supplementation with calcifediol compared to vitamin D3 and assessed the dose
      which results in mean serum 25(OH)D3 concentrations between 75 and 100 nmol/L.
      METHODS: This randomized, double-blind intervention study included men and women
      aged >=65 years (n = 59). Participants received either 5, 10 or 15 MUg
      calcifediol or 20 MUg vitamin D3 per day, for a period of 24 weeks. Blood samples
      were collected every four weeks to assess response profiles of vitamin D related
      metabolites; serum vitamin D3, 25(OH)D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)
      and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Further, serum calcium, plasma
      parathyroid hormone, and urinary calcium were evaluated. RESULTS: Supplementation
      with 20 MUg vitamin D3 increased 25(OH)D3 concentrations towards 70 nmol/L within
      16 weeks. Supplementation with 10 or 15 MUg calcifediol increased 25(OH)D3 levels
      >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12
      onwards with serum 25(OH)D3 levels stabilizing between 84 and 89 nmol/L in the 10
      MUg calcifediol group. A significant association was observed between the changes
      in 25(OH)D3 and 24,25(OH)2D3 (R2 = 0.83, P < 0.01), but not between 25(OH)D3 and
      1,25(OH)2D3 (R2 = 0.04, P = 0.18). No cases of hypercalcemia occurred in any
      treatment during the study period. CONCLUSIONS: Calcifediol supplementation
      rapidly and safely elevates serum 25(OH)D3 concentrations to improve vitamin D
      status in older adults. A daily dose of 10 MUg calcifediol allows serum 25(OH)D3
      concentrations to be maintained between 75 and 100 nmol/L. TRIAL REGISTRATION
      NUMBER: NCT01868945.

PMID- 28433268
TI  - Mumps 2017: The role of educational institutes in preventing the spread of the
      disease.

PMID- 28433269
TI  - New volatile sulfur-containing compounds from wild garlic (Allium ursinum L.,
      Liliaceae).
AB  - In many countries, the leaves of Allium ursinum L. (Liliaceae) are a popular
      substitute for garlic and, for centuries, the herb has been taken internally to
      treat an array of medical conditions. Herein, we report the chemical composition
      of 12 different A. ursinum essential-oil samples (five populations; fresh/air
      /oven-dried plant material; leaves/inflorescences). GC-MS/GC-FID analyses,
      quantitative structure-property relationship modeling (simple 0D/1D-descriptors)
      of retention indices and the synthesis of selected compounds, enabled the
      identification of >200 different constituents, mainly organo(poly)sulfides. Some
      of these were new compounds (allyl (methylthio)methyl, (methylthio)methyl (Z)/(E)
      1-propenyl and allyl 1-(methylthio)propyl disulfides) or were previously not
      detected in samples of natural origin (heptyl methyl, methyl octyl, allyl hexyl
      (1), allyl octyl (2) and propyl (propylthio)methyl sulfides). A multivariate
      statistical analysis revealed the onset of significant changes in the plant
      material volatile profile during the drying process.

PMID- 28433270
TI  - Estimate of the prevalence and burden of food poisoning by natural toxic
      compounds in South Korea.
AB  - Many studies have attempted to accurately estimate the overall number of cases of
      foodborne illness, but there have not been many attempts to estimate the burden
      of foodborne disease caused by natural toxic compounds. This study estimated the
      number of cases due to specific natural toxins (seafood toxins, plant toxins, and
      mycotoxins) during 2008-2012 in South Korea, using data from the Health Insurance
      Review and Assessment Service (HIRA), while accounting for uncertainty in the
      estimate. The estimated annual occurrences of foodborne illness from natural
      toxic agents were 1088 (90% credible interval [CrI]: 883-1315), which suggests
      there are 21 times more cases than are reported, with 45.6% (n=496 [388-614]) and
      54.4% (n=592 [423-790]), accounting for inpatient stays and outpatient visits,
      respectively. Among toxins, mushroom and plant toxins caused the highest
      illnesses, followed by toxic agents in seafood and mycotoxins. The 55-59year olds
      had the highest proportion of illnesses and those over the age of 40 accounted
      for 70.6% of all cases. The cases caused by mushroom poison, poisonous plants,
      and seafood toxins showed clear seasonal and regional differences. These results
      will be useful to food safety policymakers for the prevention and control of
      natural food poisons in South Korea.

PMID- 28433271
TI  - Environmental implications of food loss probability in packaging design.

PMID- 28433272
TI  - Digestion property and synergistic effect on biological activity of purple rice
      (Oryza sativa L.) anthocyanins subjected to a simulated gastrointestinal
      digestion in vitro.
AB  - Anthocyanins, a group of polyphenolic pigments, have been proved to possess
      various bioactivities. However, they are unstable in the small intestine and
      absorbed with low bioavailability. The discrepancy between the low
      bioavailability of anthocyanins and their good bioactivities has not been
      illuminated yet. Moreover, information about the digested property and stability
      of purple rice anthocyanins in the alimentary tract is still limited. Thus, the
      present work was designed to study the digestion property and the changes in
      antioxidant and cytoprotective activities of purple rice anthocyanins using an in
      vitro digestion model, and to investigate the interactions between gastric and
      intestinal digested anthocyanins. The results showed that anthocyanins amount and
      antioxidant and cytoprotective effects didn't change significantly during gastric
      digestion. However, about 76% of total anthocyanins were degraded during
      intestinal digestion. The IC50 values of intestinal digested sample tested by
      DPPH and ABTS methods were about 19.1 and 16.9MUg/mL, respectively, far higher
      than that of non-digested sample (about 7.7 and 7.1MUg/mL, respectively).
      Cytoprotective effect of intestinal digested sample also decreased significantly.
      Synergistic effects on antioxidant and cytoprotective activities were observed
      between the gastric and intestinal digested samples at a relative low
      concentration. Those results suggest that the bioactivities of purple rice
      anthocyanins may be changed after digestion and enhanced through the synergies
      between their gastric and intestinal digested catabolites.

PMID- 28433273
TI  - Rapid microwave assisted extraction of meat lipids.

PMID- 28433274
TI  - Stability of bioactive solid lipid nanoparticles loaded with herbal extracts when
      exposed to simulated gastrointestinal tract conditions.

PMID- 28433275
TI  - How is an ideal satiating yogurt described? A case study with added-protein
      yogurts.
AB  - Protein is recognized as the macronutrient with the highest satiating ability.
      Yogurt can be an excellent basis for designing satiating food as it is protein
      based food product. Five different set-type yogurts were formulated by adding
      extra skim milk powder (MP), whey protein concentrate (WPC), calcium caseinate
      (CAS) or a blend of whey protein concentrate with calcium caseinate (CAS-WPC). A
      control yogurt without extra protein content was also prepared. Differences in
      sensory perceptions (through CATA questions) were related to the consumers'
      expected satiating ability and liking scores (of several modalities). In
      addition, an "Ideal satiating yogurt" was included in the CATA question to
      perform a penalty analysis to show potential directions for yogurt reformulation
      and to relate sensory and non-sensory yogurt characteristics to satiating
      capacity.

PMID- 28433277
TI  - Ultrasound-assisted encapsulation of annatto seed oil: Retention and release of a
      bioactive compound with functional activities.
AB  - This paper brings forward the encapsulation of annatto seed oil (rich in
      geranylgeraniol) assisted by high intensity ultrasound using gum Arabic (GA) as
      stabilizing agent. We studied the effects of time (min) and ultrasonication power
      (W) over the emulsion characteristics. After forming microparticles from the best
      emulsion using freeze-drying (FD) and spray-drying (SD) techniques, we evaluated
      particle size distribution, moisture, water activity, surface oil, entrapment
      efficiency, encapsulation efficiency, geranylgeraniol retention, oxidative
      stability and kinetic release of geranylgeraniol, a biocompound with functional
      activities. The combined intensification of time and ultrasonication power
      reduced the superficial mean diameter (D32) and polydispersity (PDI) of
      emulsions. Drying the continuous phase of the optimized emulsion (smallest
      D32=0.69+/-0.03MUm) using FD and SD formed microparticles with different
      morphological characteristics, Brouckere diameter (D43), particle size
      distribution, moisture and water activity. SD process led to microparticles with
      the highest oil encapsulation efficiency (85.1+/-0.1wt.%) as a consequence of
      their lowest surface oil (SO). However, GA-FD microparticles presented the
      highest oil entrapment efficiency (97+/-1wt.%). Geranylgeraniol retention (80
      86wt.%) was similar for both drying techniques. GA-FD microparticles were more
      stable against oxidation through accelerated test Rancimat, even though
      presenting higher SO. This behavior is associated with the likely phase
      transition on the GA-SD matrix. The difference on the kinetic release of
      geranylgeraniol is linked to the difference on the particles morphology and
      particle size distribution.

PMID- 28433276
TI  - Comparison of TCATA and TDS for dynamic sensory characterization of food
      products.
AB  - Temporal Check-All-That-Apply (TCATA) has been recently introduced as a method
      for temporal sensory product characterization. Building on the standard Check-All
      That-Apply (CATA) question format, assessors select all the terms they consider
      applicable for describing the sensations they perceive, and they do so at each
      moment of the evaluation process. This research further investigates the TCATA
      method, through its application to products of varying complexity (yogurt,
      salami, cheese, orange juice, French bread, and marinated mussels) using
      consumers and trained panellists as assessors. More importantly, to deliver new
      methodological insights we compare TCATA to Temporal Dominance of Sensations
      (TDS). This comparison will aid researchers to select the temporal method best
      suited to their needs. Across three countries, six studies were conducted. Within
      subjects experimental designs were used in Studies 1-3 and involved trained
      panellists using both TCATA and TDS on the same set of products. In Studies 4-6,
      between-subjects experimental designs were used, and the assessors, who were
      consumers, evaluated samples using either TCATA or TDS. The results confirmed
      that TCATA is suitable for measuring the temporal sensory characteristics of
      products. By enabling identification of several sensory characteristics that are
      concurrently perceived in products, the results from this research also suggest
      that TCATA may provide a more detailed description of the dynamics of the sensory
      characteristics of products. The TDS concept of dominance appears to decrease
      detailed description and discrimination of attributes that are simultaneously
      perceived, particularly when dealing with multiple sensory modalities. The
      practical implications of these differences are discussed.

PMID- 28433278
TI  - Bioaccessibility, changes in the antioxidant potential and colonic fermentation
      of date pits and apple bagasse flours obtained from co-products during simulated
      in vitro gastrointestinal digestion.

PMID- 28433279
TI  - Development of hydrocolloid microgels as starch granule mimetics: Hydrogel
      particles fabricated from gelatin and pectin.
AB  - In this study, hydrocolloid microgels fabricated by electrostatic complexation of
      gelatin and pectin were developed as possible starch mimetics. The impact of
      covalent cross-linking on the physicochemical and structural properties of the
      microgels was investigated. Microgels were formed by acidifying a mixture of
      gelatin (0.5wt.%) and pectin (0.01wt.%) from pH10 to 5 at 40 degrees C, followed
      by cross-linking with glutaraldehyde (0 to 2mM). At low glutaraldehyde levels
      (<0.5mM), cross-linking occurred primarily within the microgels and did not
      affect particle dimensions, whereas at high levels (2mM), cross-linking connected
      adjacent microgels leading to the formation of large flocs. Rheological and
      microscopic analysis showed that the degree of cross-linking impacted the thermal
      transitions of the microgels. A simulated oral processing study indicated that
      the melt-in-the-mouth behavior of the hydrocolloid microgels could be made to be
      similar to that of starch granules by controlling the degree of cross-linking.
      This study may be useful for designing starch mimetics with improved texture
      modifying properties and reduced-calories.

PMID- 28433280
TI  - Stabilization of biopolymer microgels formed by electrostatic complexation:
      Influence of enzyme (laccase) cross-linking on pH, thermal, and mechanical
      stability.
AB  - Biopolymer microgels formed by electrostatic complexation are often susceptible
      to disintegration when environmental conditions are changed, and so methods are
      required to improve their stability. In this study, microgels were formed by
      electrostatic complexation of a protein (type-B gelatin) and a polysaccharide
      (beet pectin). The impact of enzyme (laccase) crosslinking of the ferulic acid
      groups on the beet pectin was then studied as a method to improve microgel
      stability to environmental stresses. Gelatin-beet pectin (1:0.25w/w) microgels
      were formed at 35 degrees C and pH4.4, and then the pH dependence of the zeta
      potential, size, turbidity, and microstructure of the microgels was measured in
      the absence and presence of laccase cross-linking. Our results suggested that
      crosslinking occurred within the microgels (rather than between them) since no
      particle aggregation was observed after enzyme treatment. Enzyme crosslinking did
      not affect the zeta-potential of the microgels, but it did decrease their size.
      Both cross-linked and non-cross-linked microgels were stable to aggregation at
      low (2-3) and high (4.4-7) pH values, but not at intermediate values (3-4.4),
      which was attributed to their low surface charge. Cross-linking improved the
      resistance of the microgels to shearing-induced disruption (300rpm for 24h) and
      to thermal-induced disruption (50 degrees C for 2min). These cross-linked
      biopolymer microgels may have applications for texture modification,
      encapsulation, or controlled release.

PMID- 28433281
TI  - Volatile profile of human milk subjected to high-pressure thermal processing.

PMID- 28433282
TI  - Viable and culturable populations of Saccharomyces cerevisiae, Hanseniaspora
      uvarum and Starmerella bacillaris (synonym Candida zemplinina) during Barbera
      must fermentation.
AB  - The present study analyzed the viable and/or culturable populations of
      Saccharomyces cerevisiae, Hanseniaspora uvarum and Starmerella bacillaris
      (synonym Candida zemplinina) during laboratory grape must fermentation, in order
      to investigate the interaction between the three species considered. Firstly,
      population dynamics during wine fermentation were followed by culture-dependent
      techniques, and non-Saccharomyces yeast became non-culturable at late stages of
      fermentation when S. cerevisiae dominated. Four different culture-independent
      techniques were further applied to detect viable yeast cells at the late stage of
      fermentation. Both quantitative PCR techniques applied, namely ethidium monoazide
      bromide (EMA)-qPCR and Reverse Transcription (RT)-qPCR, detected H. uvarum and
      Starm. bacillaris at a concentration of 105 to 106cells/mL. These non-culturable
      cells had membranes impermeable to EMA and stable rRNA. The background signals
      from dead cells did not interfere with the quantification of viable cells in wine
      samples by EMA-qPCR technique. As a qualitative culture-independent technique,
      DGGE technique was coupled with EMA treatment (EMA-PCR-DGGE) or with RT (RT-PCR
      DGGE). With EMA-PCR-DGGE non-Saccharomyces species during fermentation were
      detected although it was limited by the predominance of S. cerevisiae.

PMID- 28433283
TI  - The soluble recombinant N-terminal domain of HMW 1Dx5 and its aggregation
      behavior.
AB  - This study seeks to clarify and determine the fundamental properties of N
      terminal domain of high molecular weight glutenin subunits (HMW-GS) 1Dx5 (1Dx5
      N). 1Dx5-N was expressed in E. coli and its solubility was measured by
      spectrophotometry. Effects of edible salts (NaCl, Na2CO3), disulfide bond
      reductant dithiothreitol (DTT) and hydrophobic interactions of denaturant sodium
      dodecyl sulfonate (SDS) on 1Dx5-N polymer were investigated by native
      polyacrylamide gelelectrophoresis (PAGE), nonreducing/reducing SDS-PAGE,
      intrinsic fluorescence, size exclusion chromatography (SEC), dynamic light
      scattering (DLS) and circular dichroism (CD). Results showed that 1Dx5-N formed a
      soluble aggregate in aqueous solutions by native-PAGE, clarifying the role of N
      terminal of HMW-GS in the insolubility of the whole subunits. Meanwhile, the
      hydrophobic interaction was more potent in promoting the aggregation of 1Dx5-N in
      aqueous solutions from the results of SEC, DLS and CD. Edible salts, NaCl and
      Na2CO3, could improve the polymer formation of 1Dx5-N through disulfide bonds.
      Moreover, Na2CO3 at high concentrations (>200mM) greatly favored polymer
      formation by disulfide bonds, and it induced other types of cross-links between
      amino acids in 1Dx5-N according to nonreducing/reducing SDS-PAGE and fluorescence
      spectrum. Moreover, the formation of covalent bonds was reinforced by hydrophobic
      interactions between 1Dx5-N. Therefore, these results provide much novel
      information on the N-terminal domain of HMW-GS to facilitate the understanding of
      its functional properties in wheat flour.

PMID- 28433284
TI  - Effect of in vitro gastrointestinal digestion on the bioavailability of phenolic
      components and the antioxidant potentials of some Turkish fruit wines.
AB  - This study was designed to evaluate the effects of in vitro gastrointestinal
      simulation method on the antioxidant potentials and phenolic profile of some
      Turkish fruit wines and to compare the results with a Turkish red wine prepared
      from native grape varieties (Papazkarasi). For this purpose, blueberry, black
      mulberry and cherry wines were studied since they are widely consumed in Turkey.
      Papazkarasi wine was chosen due to the lack of studies regarding this type of
      wine. Antioxidant potentials of samples were measured with four different
      methods: DPPH radical-scavenging activity, H2O2-scavenging activity, cupric
      reducing capacity and total antioxidant capacity assays. The phenolic profiles of
      samples were evaluated by the determination of total phenolic content and HPLC
      DAD analysis of seven different molecules. The results of this study provided
      information not only the effect of gastrointestinal digestion on parameters
      mentioned above, but also the bioaccessibility about the phenolic compounds found
      in these four different wine samples.

PMID- 28433285
TI  - Identification of antioxidative peptides from defatted walnut meal hydrolysate
      with potential for improving learning and memory.
AB  - Defatted walnut meal (DWM), a main byproduct of walnut oil production, is rich in
      proteins with a high essential amino acid content. Our research was focused on
      the functional activities of defatted walnut meal hydrolysate (DWMH). DWMH
      exhibited relatively strong hydroxyl scavenging and oxygen radical absorbance
      capacities, protective effect on H2O2-injured PC12 cells compared with GSH and
      cerebrolysin. Besides, DWMH could combat d-galactose induced learning and memory
      impairments in the Morris water maze test and in the Dark/light avoidance test of
      mice. Seventy-seven peptides were identified by UPLC-ESI-MS/MS in the most potent
      antioxidative fraction of DWMH. WSREEQEREE and ADIYTEEAGR were the peptides that
      most likely accounted for the suppression of H2O2-induced apoptosis in PC12
      cells. The mixture of the commercially available amino acids did not offer any
      protection on H2O2-injured PC12 cells, suggesting that amino acid sequence rather
      than amino acid composition was the dominant influencing factor. DWMH could be
      recommended as natural antioxidants for the development of functional foods
      targeting memory impairments.

PMID- 28433286
TI  - Investigation and kinetic evaluation of furan formation in tomato paste and pulp
      during heating.

PMID- 28433287
TI  - Production of volatile phenols by kimchi Lactobacillus plantarum isolates and
      factors influencing their phenolic acid decarboxylase gene expression profiles.
AB  - Potential of kimchi lactic acid bacteria (LAB) isolates to produce volatile
      phenols and factors affecting their phenolic acid decarboxylase (padA) gene
      expression profiles were investigated in this study. Twelve percent (12%) of 50
      tested LAB isolates were found to decarboxylate hydroxycinnamic acids. All six
      isolates were identified as Lactobacillus plantarum and possessed the padA gene.
      The highest padA expression was achieved on the third day of incubation with
      ferulic acid, with a relative expression of 3.30+/-0.32. The effects of glucose,
      substrate, and product concentrations, and the pH of the medium were investigated
      using response surface methodology for the first time in this study. The
      expression profiles of the padA gene were diverse in various stress environments.
      The concentration of p-coumaric acid was the most significant factor being
      positively correlated with the expression levels of the padA gene, but other
      factors did not show any significant effects. High concentrations of substrates
      could confer antibacterial activity. Therefore, decarboxylation reaction was
      suggested as a bacterial response to overcome the antibacterial activity. The
      phenolic acid decarboxylase activities of L. plantarum isolates found in this
      study can provide insights for their potential application in the development of
      food-grade flavors and additives.

PMID- 28433289
TI  - Identification and quantification of phenolic and other polar compounds in the
      edible part of Annona cherimola and its by-products by HPLC-DAD-ESI-QTOF-MS.

PMID- 28433288
TI  - In vitro evidence for gut hormone stimulation release and dipeptidyl-peptidase IV
      inhibitory activity of protein hydrolysate obtained from cuttlefish (Sepia
      officinalis) viscera.

PMID- 28433290
TI  - Synthesis of potentially-bioactive lactosyl-oligofructosides by a novel bi
      enzymatic system using bacterial fructansucrases.
AB  - Efficient enzymatic synthesis of lactosyl-oligofructosides (LFOS) with a degree
      of polymerization from 4 to 8 was achieved in the presence of
      sucrose:lactosucrose and sucrose:lactose mixtures by transfructosylation
      reaction. The main synthesized LFOS which consist of beta-2,1-linked fructose to
      lactosucrose: beta-d-galactopyranosyl-(1->4)-alpha-d-glucopyranosyl-[(1->2)-beta
      d-fructofuranosyl]n-(1->2)-beta-d-fructofuranoside (where n refers to the number
      of transferred fructose moieties) was structurally characterized by nuclear
      magnetic resonance (NMR). The maximum formation of LFOS was 81% (in weight with
      respect to the initial amount of lactosucrose) and was obtained after 24h of
      transfructosylation reaction based on sucrose:lactosucrose (250gL-1 each)
      catalyzed by an inulosucrase from Lactobacillus gasseri DSM 20604 (IS). The
      production of LFOS in the presence of sucrose:lactose mixtures required a
      previous high-yield lactosucrose synthesis step catalyzed by using a levansucrase
      from Bacillus subtilis CECT 39 (LS) before the inulosucrase-catalyzed reaction.
      This novel one-pot bi-enzymatic system led to the synthesis of about 22% LFOS in
      weight, with respect to the initial amount of lactose (250gL-1). The results
      revealed a high specificity for the substrate involved in the inulosucrase
      catalyzed reaction given that, although lactosucrose (O-beta-d-galactopyranosyl
      (1->4)-O-alpha-d-glucopyranosyl-(1->2)-beta-d-fructofuranoside) acted as a strong
      acceptor of beta-2,1-linked fructose, lactose (beta-d-galactopyranosyl-(1->4)
      alpha-d-glucose) was found to be an extremely weak acceptor.

PMID- 28433291
TI  - Contributor factors for the occurrence of salmonellosis during preparation,
      storage and consumption of homemade mayonnaise salad.
AB  - This study aimed to analyze the impact of practices adopted for preparation,
      storage and consumption of homemade mayonnaise salad (HMS) as contributor factors
      for the occurrence of salmonellosis. A total of 493 individuals answered a
      questionnaire composed of demographic and socioeconomic questions and, preparing,
      storage and consumption practices of HMS. The level of good hygiene practices
      (GHP) of respondents was calculated using Good Practice and Outbreak Prevention
      Indexes. The consumer behavior and the correlation between practices were
      performed using Multiple Correspondence Analysis (MCA). 75% of respondents
      consume HMS, being 43% of interviewers doing this at least once per month. HMS
      was prepared from 30min to 1h before being served by 46% of individuals, it
      remaining for 30min to 1h at room temperature during the meal by 63% of people.
      Furthermore, 51% of respondents left the HMS container open or improperly closed,
      which may lead to cross-contamination. Most respondents (66%) stated reuse the
      HMS for less than one day (44%), at once (76%). 77% of participants declared that
      they prepare HMS, being only 7% preparing HMS without eggs. The majority (51%)
      used a cooked and a raw egg yolk. In addition, 75% of the cases showed raw eggs
      in recipe. The Weighted Good Practice Index, Weighted Outbreak Prevention Index
      and Weighted Harmonic Outbreak Prevention Index were 63%, 62% and 27% of
      participants, respectively. The MCA gathered the participants into two groups one
      commits various errors and other commits few errors on GHP. Thus, a consumer
      would probably perform multiple either good or bad practices simultaneously.

PMID- 28433292
TI  - Electrostatic spraying of organic acids on biofilms formed by E. coli O157:H7 and
      Salmonella Typhimurium on fresh produce.
AB  - Electrostatic spraying which has an even and retained surface coverage could be
      an effective novel technique to completely cover the surface of fresh produce to
      disrupt biofilm formation by pathogenic bacteria. Spinach leaves and cantaloupe
      rind were spot-inoculated with a bacterial culture and stored at 8 degrees C for
      72h to allow biofilm formation. Among various green fluorescent protein-labeled
      strains, ED 14 strain of E. coli O157:H7 and SD 10strain of Salmonella
      Typhimurium had the best attachment based on colony counts. The produce samples
      were electrostatically sprayed with malic (MA) and lactic (LA) acid solutions
      alone (1.0/2.0/3.0/4.0% w/v) or in combination (0.5+0.5/1.0+1.0/1.5+1.5/2.0+2.0%
      w/v) to test for a reduction in the attached bacteria. A combined treatment of LA
      2.0% w/v+MA 2.0% w/v had the highest log reduction (CFU/disk) of 4.14 and 3.6 on
      the attached E. coli strain ED 14 (spinach) and Salmonella strain SD 10
      (cantaloupe), respectively. Crystal violet assay demonstrated the disruptive
      effect of organic acids on biofilms formed by the pathogenic bacteria.
      Application of electrostatic spray with a combination of malic and lactic acids
      resulting in a log reduction (CFU/disk) of 3.6 or higher can improve the
      microbial safety of spinach and cantaloupe by preventing the pathogenic biofilm
      formation and bacterial growth.

PMID- 28433293
TI  - Comparative proteomic approaches to analysis of litchi pulp senescence after
      harvest.
AB  - Litchi fruit (Litchi chinensis Sonn.) is highly perishable after harvest. The
      shelf life is only 4-6days under ambient temperature storage conditions, which
      has restricted the development of the litchi industry to a considerable extent.
      To investigate the molecular mechanisms of litchi fruit senescence, comparative
      proteomic analysis was carried out on litchi pulp. After two-dimensional gel
      electrophoresis (2-DE), 64 spots were significantly differentially expressed, 61
      of which were successfully identified using liquid chromatography-electrospray
      ionization-tandem mass spectrometry (LC-ESI-MS/MS). All of the identified
      proteins were classified according to biological process, molecular function, and
      cellular component using Blast2GO. Results showed that those proteins were mainly
      involved in signal transduction, cell wall metabolism, primary and secondary
      metabolism, energy metabolism. Specifically, many up-regulated proteins were
      involved in auxin/ethylene regulation, which suggested that auxin and ethylene
      might cooperate to regulate litchi pulp senescence. Histone deacetylase and DNA
      methyltransferase might involve the down-regulation of proteins related to
      reactive oxygen species (ROS) scavenging, glycolysis, tricarboxylic acid cycle,
      and ATP synthesis in litchi senescence. A higher proportion of differentially
      expressed proteins were up-regulated and these were involved in a range of
      processes including cell wall organization or biogenesis, anaerobic respiration,
      protein degradation, lipid degradation. All of those proteins might accelerate
      fruit softening, deterioration and senescence. This study is the first to carry
      out proteomic analysis of the regulation of litchi fruit senescence.

PMID- 28433294
TI  - Phytochemicals and bioactive properties of Ilex paraguariensis: An in-vitro
      comparative study between the whole plant, leaves and stems.
AB  - The leaves, stems and whole plant of Ilex paraguariensis (yerba mate) were
      characterized in terms of their chemical composition and biological activities in
      order to determine which part of the plant is more interesting to develop
      bioactive formulations. The yerba mate samples contain at least five free sugars,
      five organic acids, eighteen fatty acids, one tocopherol, nine hydroxycinnamoyl
      derivatives and two flavonols. The leaf extract revealed the highest antioxidant
      activity, correlating with its highest levels of phenolic compounds. By contrast,
      the stem extract showed the highest anti-inflammatory potential and was also the
      most potent against MCF-7 and HepG2 cell lines, probably due to the presence of
      other phytochemicals. The absence of hepatotoxicity in the extracts was confirmed
      in porcine liver primary cells. Although the yerba mate extracts have been widely
      studied, this report shows for the first time the distinct potentialities of each
      individual part of the plant.

PMID- 28433295
TI  - Novel methodology for the in situ assessment of CO2 production rate and its
      application to anaerobic ripened cheese.
AB  - CO2 is produced by many microorganisms present in cheese and it can affect cheese
      quality both during processing and storage. The knowledge of the extent of CO2
      production by cheese microorganism (CO2 production rate coefficients) may be used
      to predict gas exchange in cheese/packaging systems, helping dairy industries in
      the right choice of the packaging (higher/lower gas permeability) and mastering
      of cheese ripening. However very few coefficients for CO2 production rate have
      been published and the ones assessed in vitro (not inside real food) may not well
      describe the activity of the microorganisms in situ. We have therefore developed
      a methodology for the in situ assessment of CO2 production rate and applied it to
      cheese with propionic acid fermentation. The proposed methodology is based on
      infra-red measurement of CO2 and it allows measuring its accumulation up to 1%
      with 0.001% resolution, while monitoring the level of oxygen. The method showed a
      good repeatability, with a low coefficient of variation within samples (6.6%) and
      between samples (8.4%) compared to 10-30% between samples found in literature.
      The method was compared with a gas chromatography based method, which is also
      described.

PMID- 28433296
TI  - Adaptability of some French red grape varieties cultivated at two different
      Portuguese terroirs: Comparative analysis with two Portuguese red grape varieties
      using physicochemical and phenolic parameters.

PMID- 28433297
TI  - Copigmentation between malvidin-3-O-glucoside and hydroxycinnamic acids in red
      wine model solutions: Investigations with experimental and theoretical methods.
AB  - The copigmentation effect between malvidin-3-O-glucoside and three
      hydroxycinnamic acids (p-coumaric, caffeic and ferulic acids) on the color
      expression was assessed in red wine model solutions. The colorimetric parameters
      indicated that the increasing concentration of these copigments could enhance the
      color intensity of the wine-like solutions (hyperchromic effect and bathochromic
      shift), and displayed the darker and more vivid bluish chromatic properties. The
      equilibrium constant (K), stoichiometric ratio (n) and thermodynamic parameters
      (?G degrees , ?H degrees , ?S degrees ) were determined by the spectrophotometric
      methods, showing the generally spontaneous exothermic character of the process.
      In addition, quantum chemical investigations were performed to interpret the
      absorption differences. The results showed that the ferulic acid was the more
      powerful copigment compared with the other two hydroxycinnamic counterparts,
      indicating that the copigmentation was not only correlated to the concentration
      of the copigments but also strongly dependent on their molecular structures. AIM
      analysis was also used to explore the driving forces contributing to the
      copigmentation, which suggested that the hydrogen bond and van der Waals
      interactions were the main driving forces for the three pigment-copigment
      complexes.

PMID- 28433298
TI  - How do consumers describe wine astringency?
AB  - Astringency is one of the most important sensory characteristics of red wine.
      Although a hierarchically structured vocabulary to describe the mouthfeel
      sensations of red wine has been proposed, research on consumers' astringency
      vocabulary is lacking. In this context, the aim of this work was to gain an
      insight on the vocabulary used by wine consumers to describe the astringency of
      red wine and to evaluate the influence of wine involvement on consumers'
      vocabulary. One hundred and twenty-five wine consumers completed and on-line
      survey with five tasks: an open-ended question about the definition of wine
      astringency, free listing the sensations perceived when drinking an astringent
      wine, free listing the words they would use to describe the astringency of a red
      wine, a CATA question with 44 terms used in the literature to describe
      astringency, and a wine involvement questionnaire. When thinking about wine
      astringency consumers freely elicited terms included in the Mouth-feel Wheel,
      such as dryness and harsh. The majority of the specific sub-qualities of the
      Mouth-feel Wheel were not included in consumer responses. Also, terms not
      classified as astringency descriptors were elicited (e.g. acid and bitter). Only
      17 out of the 31 terms from the Mouth-feel Wheel were used by more than 10% of
      participants when answering the CATA question. There were no large differences in
      the responses of consumer segments with different wine involvement. Results from
      the present work suggest that most of the terms of the Mouth-feel Wheel might not
      be adequate to communicate the astringency characteristics of red wine to
      consumers.

PMID- 28433299
TI  - Volatiles and primary metabolites profiling in two Hibiscus sabdariffa (roselle)
      cultivars via headspace SPME-GC-MS and chemometrics.
AB  - Hibiscus sabdariffa (roselle) is a plant of considerable commercial importance
      worldwide as functional food due to its organic acids, mucilage, anthocyanins,
      macro and micro-nutrients content. Although Hibiscus flowers are emerging as very
      competitive targets for phytochemical studies, very little is known about their
      volatile composition and or aroma, such knowledge can be suspected to be relevant
      for understanding its olfactory and taste properties. To provide insight into
      Hibiscus flower aroma composition and for its future use in food and or
      pharmaceutical industry, volatile constituents from 2 cultivars grown in Egypt,
      viz. Aswan and Sudan-1 were profiled using solid-phase microextraction (SPME)
      coupled to GCMS. A total of 104 volatiles were identified with sugar and fatty
      acid derived volatiles amounting for the major volatile classes. To reveal for
      cultivar effect on volatile composition in an untargeted manner, multivariate
      data analysis was applied. Orthogonal projection to latent structures
      discriminant analysis (OPLS-DA) revealed for 1-octen-3-ol versus furfural/acetic
      acid enrichment in Aswan and Sudan-1 cvs., respectively. Primary metabolites
      contributing to roselle taste and nutritional value viz. sugars and organic acids
      were profiled using GC-MS after silylation. The impact of probiotic bacteria on
      roselle infusion aroma profile was further assessed and revealed for the increase
      in furfural production with Lactobacillus plantarum inoculation and without
      affecting its anthocyanin content. This study provides the most complete map for
      volatiles, sugars and organic acids distribution in two Hibiscus flower cultivars
      and its fermented product.

PMID- 28433300
TI  - Crust morphology and crispness development during deep-fat frying of potato.
AB  - Crust formation is an important factor in determining the crispness of French
      fries. This study aimed at unravelling detailed structural and textural
      properties of the crust in relation to crispness during frying as a function of
      the process temperature and time. X-ray tomography showed a larger overall pore
      volume at higher frying times, while a lower final moisture content mainly
      resulted in an increase in the amount of large pores. Texture analysis revealed
      that the increase in porosity, due to the increased formation of pores, results
      in a more crispy behaviour after frying with oil of up to 180 degrees C. At
      temperatures above 180 degrees C crispness is actually found to decrease again,
      which is explained by the increased plastic behaviour of the crust. This may be
      related to the reduced glass transition temperature of the crust because of
      increased sugar degradation at a very high temperature.

PMID- 28433301
TI  - Eggshell penetration by Salmonella Typhimurium in table eggs: Examination of
      underlying eggshell structures by micro-computed tomography and scanning electron
      microscopy.
AB  - Horizontal infection of table eggs by food borne, human infection causative
      agents such as Salmonella is a serious concern for consumers and industry. In
      this study, we investigated the relationship between eggshell translucency,
      mammillary layer abnormalities and pore structure using Computed Tomography (CT)
      and scanning electron microscopy. The effects of eggshell pore structure, size
      and number on Salmonella Typhimurium penetration was also investigated. The eggs
      were infected with S. Typhimurium and were incubated at 37 degrees C for 3 or
      6days. Micro CT results comparing shell features to shell translucency found that
      there was a significantly increased incidence of externally branching pores found
      in the high translucency score eggshell group, and more straight pores found in
      the low translucency score group. Different pore structures, the total number of
      pores and the shell thickness do not appear to play a role in the horizontal
      infection of eggs by the S. Typhimurium strain used in this study. While it is
      likely that the presence of shell pores is responsible for shell penetration,
      other unknown shell factors must also play a role, and eggshells with a higher
      incidence of shell pores are not penetrated at a higher rate.

PMID- 28433302
TI  - Metabolomics of Lonicera caerulea fruit during ripening and its relationship with
      color and antioxidant activity.
AB  - We performed mass spectrometry-based metabolites profiling in Lonicera caerulea
      fruits according to seven ripening stages. During ripening, fruit color
      significantly changed from green to red, with sugars, organic acids, phenolic
      acids, anthocyanins, and flavonoids significantly altered. In particular, the
      contents of cyanidin-3-glucoside, peonidin-glucoside, peonidin-3-rutinoside and
      cyanidin-3-rutinoside, which are closely associated with color, were elevated
      from stages four to seven. The changes of antioxidant activity during ripening
      were similar to those of total phenolic and flavonoid contents. L. caerulea
      fruits at stage six (pale-purple) had higher antioxidant activity and total
      phenolic and flavonoid contents with higher cyanidin-3,5-diglucoside contents
      than those at stage seven (fully purple). From this study, we revealed the
      changes in the contents of primary and secondary metabolites with antioxidant
      properties during ripening, and these results could be helpful to determine the
      optimal harvest stage of L. caerulea fruit.

PMID- 28433303
TI  - Apple, grape or orange juice: Which one offers the best substrate for
      lactobacilli growth? - A screening study on bacteria viability, superoxide
      dismutase activity, folates production and hedonic characteristics.

PMID- 28433304
TI  - Identification of novel saponins in vegetable amaranth and characterization of
      their hemolytic activity.

PMID- 28433305
TI  - Relating dynamic perception of reformulated cheese pies to consumers'
      expectations of satiating ability.
AB  - Designing satiating food is not an easy task. Food reformulation is normally done
      by altering the proportion of basic ingredients or by adding new minor
      ingredients. In general, the texture varies concomitantly with these changes,
      altering the way the food is processed orally and the complete eating experience.
      This highlights the interest of discovering how variations in minor ingredients
      influence texture and how this affects the dynamics of the oral trajectory. Six
      cheese pie formulations were prepared: basic recipe (Base), no egg (-Egg), no
      corn starch (-Corn starch) no sugar (-Sugar), added diary cream (+Cream) and
      extra skimmed milk powder (+Milk powder). Temporal dominance of sensations was
      used to show that the appearance and disappearance of each texture sensation
      dominance experienced in the mouth during the eating process differed among the
      six pies, as did their relation to the consumers' expectation of satiating
      capacity scores and to the changes in composition. Two extreme behaviors were
      found: suppression of egg/addition of extra milk powder made the pies initially
      drier and harder, while suppression of corn starch/addition of cream gave the
      samples a soft, moist early sensation. The former elicited higher expectations of
      satiating capacity. In addition, overall liking, liking evolving with time
      (dynamic liking) and the level of several key texture attributes' divergence from
      those of an "ideal" cheese pie were evaluated on bipolar just-about-right scales
      and through penalty analysis to gain insights into potential directions for
      reformulating acceptable pies.

PMID- 28433306
TI  - Impact of in vitro simulated digestion on the potential health benefits of
      proanthocyanidins from Choerospondias axillaris peels.
AB  - The influence of passage through a simulated gastrointestinal tract (GIT) on the
      stability and bioaccessibility of proanthocyanidins isolated from fruit
      (Choerospondias axillaris) peel was studied. In addition, the effects of the
      simulated GIT on the antioxidant and alpha-glucosidase inhibitory activities of
      proanthocyanidins extracts were evaluated. Gastric digestion had little effect on
      total polyphenol content (TPC) or mean degree of polymerization (mDP) of crude
      and purified extracts. However, intestinal digestion led to a significant
      decrease (about 26% and 19%) in TPC and (about 12% and 7%) in mDP for crude and
      purified extracts, respectively. The observed reduction in TPC and mDP levels was
      attributed to interactions of proanthocyanidins with pancreatic enzymes, rather
      than due to the chemical conditions during digestion. Only small flavan-3-ol
      molecules (monomers, dimers and trimers) could diffuse into the dialysis tubing
      used to simulate the intestinal wall. Changes in antioxidant activity during
      digestion were correlated to changes in TPC. After simulated GIT digestion, over
      85% of alpha-glucosidase inhibitory activity of both extracts was preserved.
      These results indicate that the majority of the proanthocyanidins maintained
      their biological activities after passage through the simulated GIT, and were
      therefore still capable of providing valuable health benefits.

PMID- 28433307
TI  - Simulating shelf life determination by two simultaneous criteria.
AB  - The shelf life of food and pharmaceutical products is frequently determined by a
      marker's concentration or quality index falling below or surpassing an assigned
      threshold level. Naturally, different chosen markers would indicate different
      shelf life for the same storage temperature history. We demonstrate that if there
      are two markers, such as two labile vitamins, the order in which their
      concentrations cross their respective thresholds may depend not only on their
      degradation kinetic parameters but also on the particular storage temperature
      profile, be it isothermal or non-isothermal. Thus, at least theoretically, the
      order observed in accelerated storage need not be always indicative of the actual
      order at colder temperatures, except where the two degradation reactions follow
      the same kinetic order and their temperature-dependence rate parameter is also
      the same. This is shown with simulated hypothetical degradation reactions that
      follow first or zero order kinetics and whose rate constant's temperature
      dependence obeys the exponential model. It is also demonstrated with simulated
      hypothetical Maillard reaction's products whose synthesis rather than their
      degradation follows pseudo zero order kinetics. The software developed to do the
      simulations and calculate the thresholds crossing points has been posted on the
      Internet as a freely downloadable interactive Wolfram Demonstration, which can be
      used as a tool in storage studies and shelf life prediction. In principle, the
      methodology can be extended from two to any number of markers.

PMID- 28433308
TI  - Quality changes of pasteurised mango juice during storage. Part I: Selecting
      shelf-life markers by integration of a targeted and untargeted multivariate
      approach.
AB  - For the first time, a multivariate approach combining targeted and untargeted
      data was used to obtain insight into quality changes in pasteurised mango juice
      (cv. 'Totapuri') as a function of storage (42 degrees C for 8weeks). Mango juice
      samples were formulated with addition of different potential precursors for
      different quality-related chemical reactions: ascorbic acid, citric acid and
      sugars. Control (diluted mango puree with water), ascorbic acid-enriched (AA250
      and AA500), citric acid-enriched (CA, CA+AA250 and CA+AA500) and sugar-enriched
      (S) samples were characterised for a range of targeted quality parameters as well
      as for a volatile fingerprint (untargeted). Selection of shelf-life markers or
      quality parameters significantly changing during shelf-life was performed over
      all formulations as well as per mango juice formulation. Our study showed that a
      common trend over all formulations was observed for colour values (VID>?0.90?),
      while specific shelf-life markers were selected for each formulation. In
      acidified mango juice samples (CA, CA+AA250, CA+AA500), more terpene oxides were
      selected compared to other formulations. In ascorbic acid-enriched samples
      (AA250, AA500, CA+AA250, CA+AA500), furfural and ascorbic acid were significantly
      changing during shelf-life. It seems that the reaction pathways for compounds
      being formed or degraded upon shelf-life are clearly affected by the acidity
      level.

PMID- 28433309
TI  - Proteomic and peptidomic insights on myofibrillar protein hydrolysis in a sausage
      model during fermentation with autochthonous starter cultures.
AB  - The hydrolysis of myofibrillar proteins during fermentation of sausage models by
      an autochthonous starter culture was investigated. In order to provide a whole
      map of the generated products, proteomic and peptidomic were used and
      complemented with the amino acid profile. Beaker sausages (BS) were used as
      models which were inoculated or not with Lactobacillus curvatus CRL705 and
      Staphylococcus vitulinus GV318 as starter cultures. The hydrolysis of actin,
      myosin light chain 1/3 (MLC 1/3), myosin regulatory light chain-2 (MRLC-2) and
      myosin heavy chain (MHC) was evidenced by two-dimensional gel electrophoresis (2
      DE). In addition, a total of 33 peptides arisen from troponin T, MRLC-2 and
      particularly from actin were identified by LC-MS/MS. These results showed that
      the starter culture significantly enhanced the proteolysis of the proteins named
      above, even when the endogenous enzymes induced a clear breakdown. L. curvatus
      CRL705 highly enriched both peptide pattern and amino acid concentrations. When
      the autochthonous starter culture was inoculated, although proteolysis was
      remarkably reinforced, a reduction in peptide and amino acid composition was
      observed. Regarding actin primary structure, three regions of this protein were
      highly susceptible to degradation by the starter culture. Additionally, the
      essential role of exopeptidases - from meat and bacteria - in diversity of actin
      peptides during fermentation was shown. This study improved the knowledge of the
      proteolysis of myofibrillar proteins and the involved enzymes, as well as,
      completed the previously reported degradation of sarcoplasmic proteins by the
      same autochthonous starter culture. The singular peptides and amino acids pattern
      generated might contribute to the uniqueness of produced fermented sausages while
      they may be used as quality markers.

PMID- 28433310
TI  - Quality changes of pasteurised mango juice during storage. Part II: Kinetic
      modelling of the shelf-life markers.
AB  - The present work shows the potential of the integrated fingerprinting-kinetics
      approach in evaluating shelf-life changes of pasteurised mango juice (cv.
      'Totapuri'). Seven mango juice formulations (i.e. control (mango puree and
      water), ascorbic acid-enriched (AA250 and AA500), citric acid-enriched (CA,
      CA+AA250 and CA+AA500) and sugar-enriched (S) samples) were pasteurised and
      stored at 42 degrees C for 8weeks. In this part, the kinetics of the shelf-life
      markers selected from the multivariate fingerprinting approach was modelled.
      Changes in selected targeted parameters could be best described by a zero-order
      (colour values,  degrees Brix, furfural, HMF), a first-order (ascorbic acid), a
      fractional conversion (fructose, glucose, oxygen) and a second-order model
      (sucrose). Differences in the rate constant were observed, with faster ascorbic
      acid degradation and furfural formation in AA-enriched samples and faster
      hydrolysis of sugars and HMF formation in CA-enriched samples compared to control
      samples. To describe changes in selected volatiles (terpenes, sulphur compounds,
      acids, ketones and esters), different kinetic models were selected. Two trends
      were observed: changes as affected by different mango juice formulations (e.g.,
      faster reaction in CA-enriched samples or in a lower pH condition) and changes
      irrespective of the formulations. Referring to the literature, in general, acid
      catalysed reactions, ascorbic acid degradation and oxidation reactions are the
      main reactions responsible for the observed quality changes in stored mango
      juice.

PMID- 28433311
TI  - Effect of processing conditions on quality of green beans subjected to
      reciprocating agitation thermal processing.
AB  - The effect of reciprocating agitation thermal processing (RA-TP) on quality of
      canned beans was evaluated in a lab-scale reciprocating retort. Green beans were
      selected due to their soft texture and sensitive color. Green beans (2.5cm
      length*0.8cm diameter) were filled into 307*409 cans with carboxylmethylcellulose
      (0-2%) solutions and processed at different temperatures (110-130 degrees C) and
      reciprocation frequency (1-3Hz) for predetermined heating times to achieve a
      process lethality (Fo) of 10min. Products processed at higher temperatures and
      higher reciprocation frequencies resulted in better retention of chlorophyll and
      antioxidant activity. However, high reciprocation frequency also resulted in
      texture losses, with higher breakage of beans, increased turbidity and higher
      leaching. There was total loss of product quality at the highest agitation speed,
      especially with low viscosity covering solutions. Results suggest that
      reciprocating agitation frequency needs to be adequately moderated to get the
      best quality. For getting best quality, particularly for canned liquid
      particulate foods with soft particulates and those susceptible to high impact
      agitation, a gentle reciprocating motion (~1Hz) would be a good compromise.

PMID- 28433312
TI  - Silver/chitosan-based Janus particles: Synthesis, characterization, and
      assessment of antimicrobial activity in vivo and vitro.
AB  - Janus particles containing chitosan and silver were synthesized in an eco
      friendly manner and were confirmed using transmission electron microscopy. Based
      on the data of the antimicrobial activity assessment, this material exhibited a
      higher antimicrobial activity than virgin chitosan with long-lasting
      antibacterial effectiveness against Staphylococcus aureus, Bacillus subtilis,
      Escherichia coli and Salmonella choleraesuis bacteria, as well as Botrytis
      cinerea fungi. The results showed that the Janus polymer could completely
      suppress the growth and germination of B. cinerea at a concentration of 0.02mg/mL
      in vitro and in vivo. This Janus polymer is an advanced functional material that
      combines the suitable properties of both components and could be an alternative
      new antimicrobial agent due to its unique chemical properties and pronounced
      antimicrobial activity. This material is a potential candidate for use in the
      food industry to prevent microbial contamination and to inhibit the growth of
      microorganisms, enhancing product quality and, extend shelf-life of fresh and
      processed agri-food products.

PMID- 28433313
TI  - Flavonol profile of cactus fruits (Opuntia ficus-indica) enriched cereal-based
      extrudates: Authenticity and impact of extrusion.

PMID- 28433314
TI  - Approaches for the assembly of molecularly imprinted electrospun nanofibre
      membranes and consequent use in selected target recognition.

PMID- 28433315
TI  - New insights in antibiotic resistance of Lactobacillus species from fermented
      foods.

PMID- 28433316
TI  - Effect of pH, sodium chloride and sodium pyrophosphate on the thermal resistance
      of Escherichia coli O157:H7 in ground beef.

PMID- 28433317
TI  - Relating physicochemical and microbiological safety indicators during processing
      of linguica, a Portuguese traditional dry-fermented sausage.
AB  - Linguica is a Portuguese traditional fermented sausage whose microbiological
      quality and safety can be highly variable. In order to elucidate risk factors and
      the particularities of the manufacturing technology that explain the between
      batch variability in total viable counts (TVC), Enterobacteriaceae,
      Staphylococcus aureus and Listeria monocytogenes in the product; microbiological
      and physicochemical characterisation of linguica at five stages of production
      (i.e., raw pork meat, mixed with ingredients, macerated, smoked and ripened) was
      carried out. A total of six production batches were surveyed from two factories;
      one utilised curing salts and polyphosphate in their formulation (Factory II).
      The delayed fermentation in the nitrite-formulated sausages was partly
      responsible for the increase (p<0.01) in Enterobacteriaceae, S. aureus and L.
      monocytogenes from raw meat (3.21logCFU/g, 1.30logCFU/g and 22.2CFU/g,
      respectively) to the end of maceration (4.14logCFU/g, 2.10logCFU/g and 140CFU/g,
      respectively) while the better acidification process in the nitrite-free sausages
      (Factory I) led to lower counts of S. aureus (2.64logCFU/g) and L. monocytogenes
      (10CFU/g) in the finished products. In Factory II, although L. monocytogenes
      entered the chain at the point of mixing, it became steadily inactivated during
      smoking and ripening (<50CFU/g), despite the initially-delayed fermentation.
      Nitrite had a strong effect on reducing Enterobacteriaceae throughout smoking (r=
      0.73) and ripening (r=-0.59), while it failed to control the growth of S. aureus.
      The main hurdle preventing the development of S. aureus in linguica is the pH,
      and other factors contributing to its control are: longer ripening days
      (p=0.019), low S. aureus in raw meat (p=0.098), properly-washed casings
      (p=0.094), and less contamination during mixing (p=0.199). In the case of L.
      monocytogenes, at least three hurdles hinder its development in linguica: low aw
      (p=0.004), low pH (p=0.040) and nitrite (p=0.060), and other factors contributing
      to its control are: longer ripening (p=0.072) and maceration (p=0.106) periods,
      lower aw at the end of smoking (p=0.076) and properly-washed casings (p=0.099).
      Results have shown that there is a need to standardise the productive process of
      linguica, to optimise the initial acidification process, and to reinforce proper
      programmes of quality control of ingredients and good hygiene practices, so as to
      minimise the introduction of Enterobacteriaceae and pathogens from external
      sources.

PMID- 28433318
TI  - Physicochemical properties of different thickeners used in infant foods and their
      relationship with mineral availability during in vitro digestion process.
AB  - Locust bean gum (LBG) and modified starches are commonly used as thickeners in
      food products for infants. However, there is no consensus on their possible
      effects on infant nutrition, especially on mineral availability. The aim of the
      present work was to characterize the effect of LBG, cross-linked,
      hydroxypropylated maize starch (Mhdp) and pre-gelatinized rice starch (gRS) on
      Ca, Fe and Zn availability during a gastric and intestinal in vitro digestion
      assay in relation to their physicochemical properties in solution (apparent
      viscosity, solubility, molar mass (M) and conformational properties) through the
      simulated digestion process. LBG gave the highest decrease in Ca and Fe gastric
      (17.96% and 17.6% respectively) and intestinal (19.5% and 13.5%) solubility with
      respect to the reference without thickeners. Ca (11.1%+/-1.1), Fe (2.77%+/-0.3)
      and Zn (7.78%+/-0.6) dialyzability was also lower than for the reference (23.4%+/
      2.9; 19.65%+/-3.53 and 27.74%+/-3.3 respectively). LBG solubility remained stable
      during gastric digestion, decreasing significantly from a range of 65-69% to
      61.1% after intestinal digestion. LBG viscosity remained stable during the
      digestion process, being these findings attributable to its resistance to
      enzymes. On the other hand, the addition to Mhdp or gRS slightly affected Ca and
      Fe solubility or Ca dialyzability, decreasing after gastric digestion and then
      increasing after intestinal digestion with respect to the reference. These
      results correlated to the changes in their viscosity enhancing properties, which
      increased during gastric digestion and decreased after intestinal digestion,
      being attributable to their digestion by pancreatic enzymes. Gastric digestion
      resulted in an increase in M for the modified starches (more pronounced for gRS).
      The increase in mineral solubility and dialyzability after intestinal digestion
      with respect to the gastric stage was explained by the degradation of starches by
      intestinal enzymes, which resulted in a decrease in apparent shear viscosity
      (from 1.2 to 1Pas, measured in a shear rate range 0.00-50s-1) and an increase in
      solubility (from 3 to 6% to approximately 70%) after intestinal digestion. In
      conclusion, LBG could be more effective than Mhdp and gRS as thickener, providing
      higher viscosity and resistance to digestive process. However, its negative
      effect on mineral solubility and dialyzability should be taken into account. On
      the contrary, Mhdp and gRS showed to be degraded after intestinal digestion.

PMID- 28433319
TI  - Antihypertensive effect of peptides naturally generated during Iberian dry-cured
      ham processing.

PMID- 28433320
TI  - Simulated gastrointestinal fate of lipids encapsulated in starch hydrogels:
      Impact of normal and high amylose corn starch.
AB  - The influence of starch type (resistant starch (RS) versus native (NS) starch)
      and concentration (10 and 35wt.%) on the potential gastrointestinal fate of
      digestible lipid (corn oil) droplets encapsulated within starch hydrogels was
      studied using a simulated gastrointestinal tract (GIT). The NS used was a normal
      corn starch, whereas the RS used was a high amylose corn starch. Changes in
      morphology, organization, size, and charge of the particles in the delivery
      systems were measured as they passed through each stage of the GIT model: mouth,
      stomach, and small intestine. The GIT fates of three types of delivery system
      were compared: free lipid droplets; lipid droplets in RS-hydrogels; and, lipid
      droplets in NS-hydrogels. Encapsulation of the lipid droplets in the hydrogels
      had a pronounced influence on their GIT behavior, with the effect depending
      strongly on starch type. The starch granules in the RS-hydrogels remained intact
      throughout the simulated GIT because their compact structure makes them resistant
      to enzyme digestion. The initial rate of lipid digestion in the small intestine
      phase also depended on delivery system type: emulsion>RS-hydrogels>NS-hydrogels.
      However, the lipid phase appeared to be fully digested at the end of the
      digestion period for all samples. These results provide useful information for
      designing functional foods for improved health. For example, food matrices could
      be developed that slowdown the rate of lipid digestion, and therefore prevent a
      spike in serum triacylglycerols in the blood, which may be advantageous for
      developing functional foods to tackle diabetes.

PMID- 28433321
TI  - Consumer perception of carriers of a satiating compound. Influence of front-of
      package images and weight loss-related information.
AB  - Nowadays it is common to find dietary supplements on the market with the same
      health promoting compounds as certain functional food products. However, there is
      a lack of research comparing these two categories of carriers (food and
      supplements) for the same functional ingredient. This work focuses on konjac
      glucomannan (KGM) due to its recognized body weight reduction-related effect:
      when it swells in the stomach in the presence of sufficient water, it produces a
      sensation of fullness. In this context, the objectives of the present work were
      to gain knowledge about consumer perception of KGM and its different carriers or
      forms of presentation (in a food item or in capsules). In addition, the relative
      importance of the carrier, front-of-package images and weight loss-related
      information were studied by different sensory techniques, such as word
      association, projective mapping and conjoint analysis. The results showed that
      consumers formed negative perceptions when the information was not sufficiently
      complete and that they considered a food product containing KGM better than KGM
      capsules. Regarding the front of the package, health benefit-related images were
      more attractive than verbal information.

PMID- 28433322
TI  - An integrated method for the emotional conceptualization and sensory
      characterization of food products: The EmoSensory(r) Wheel.
AB  - Although acceptability is commonly used to examine liking for food products, more
      studies now emphasize the importance of measuring consumers' conceptualizations,
      such as emotions for food products. It is also important to identify how
      consumers perceive the sensory attributes of food products, as illustrated by the
      increasing involvement of consumers in product characterization. The objective of
      this paper is to examine the use of a wheel-format questionnaire to obtain both
      an emotional and sensory profiles for food products using a hands-on consumer
      tool. Terms selected were product-specific and the rate-all-that-apply (RATA)
      approach was used as a scaling technique. Three different experiments
      demonstrated that the EmoSensory(r) Wheel could discriminate within and between
      food product categories. The added value of the RATA approach was illustrated in
      the sample discrimination for some food products when using the weighted
      attribute scores for analysis. The tool was used in both blind and informed
      conditions to illustrate its applicability across different experimental designs.
      In general, the respondents did not find the task tedious when using the wheel
      questionnaire format, demonstrating the potential for collecting information in a
      more facile way. Although further studies with other food products are needed,
      this paper shows the potential for using this wheel format to obtain information
      about consumers' emotional and sensory profiling of food products.

PMID- 28433323
TI  - Is there a clinically meaningful difference in patient reported dyspnea in acute
      heart failure? An analysis from URGENT Dyspnea.
AB  - BACKGROUND: Dyspnea is the most common presenting symptom in patients with acute
      heart failure (AHF), but is difficult to quantify as a research measure. The
      URGENT Dyspnea study compared 3 scales: (1) 10 cm VAS, (2) 5-point Likert, and
      (3) a 7-point Likert (both VAS and 5-point Likert were recorded in the upright
      and supine positions). However, the minimal clinically important difference
      (MCID) to patients has not been well established. METHODS: We performed a
      secondary analysis from URGENT Dyspnea, an observational, multi-center study of
      AHF patients enrolled within 1 h of first physician assessment in the ED. Using
      the anchor-based method to determine the MCID, a one-category change in the 7
      point Likert was used as the criterion standard ('minimally improved or worse').
      The main outcome measures were the change in visual analog scale (VAS) and 5
      point Likert scale from baseline to 6-h assessment relative to a 1-category
      change response in the 7-point Likert scale ('minimally worse', 'no change', or
      'minimally better'). RESULTS: Of the 776 patients enrolled, 491 had a final
      diagnosis of AHF with responses at both time points. A 10.5 mm (SD 1.6 mm) change
      in VAS was the MCID for improvement in the upright position, and 14.5 mm (SD 2.0
      mm) in the supine position. However, there was no MCID for worsening, as few
      patients reported worse dyspnea. There was also no significant MCID for the 5
      point Likert scale. CONCLUSION: A 10.5 mm change is the MCID for improvement in
      dyspnea over 6 h in ED patients with AHF.

PMID- 28433324
TI  - Stakeholder views on criteria and processes for priority setting in Norway: a
      qualitative study.
AB  - Since 2013, Norway has engaged in political processes to revise criteria for
      priority setting. These processes have yielded key efficiency and equity
      criteria, but excluded potentially relevant social values. This study describes
      the views of 27 stakeholders in Norway's health system regarding a wider set of
      priority-setting criteria and procedural characteristics. Between January and
      February 2016, semi-structured interviews and focus groups were conducted with a
      purposive sample of policymakers, hospital administrators, practitioners,
      university students and seniors. Improving health among low-socioeconomic-status
      groups was considered an important policy objective: some favored giving more
      priority to diseases affecting socioeconomically disadvantaged groups, and some
      believed inequalities in health could be more effectively addressed outside the
      health sector. Age was not widely accepted as an independent criterion, but
      deemed relevant as an indicator of capacity to benefit, cost-effectiveness and
      health loss. Cost-effectiveness, severity and health-loss measures were judged
      relevant to policymaking, but cost-effectiveness and health loss were considered
      less influential to clinical decision-making. Public engagement was seen as
      essential yet complicated by media and stakeholder pressures. This study
      highlights how views on the relevance and implementation of criteria can vary
      significantly according to the health system level being evaluated. Further, the
      findings suggest that giving priority to socioeconomically disadvantaged groups
      and reducing inequalities in health may be relevant preferences not captured in
      recent policy proposals.

PMID- 28433325
TI  - The role of private non-profit healthcare organizations in NHS systems:
      Implications for the Portuguese hospital devolution program.
AB  - The national health services (NHS) of England, Portugal, Finland and other single
      payer universalist systems financed by general taxation, are based on the
      theoretical principle of an integrated public sector payer-provider. However, in
      practice one can find different forms of participation of non-public healthcare
      providers in those NHS, including private for profit providers, but also third
      sector non-profit organizations (NPO). This paper reviews the role of non-public
      non-profit healthcare organizations in NHS systems. By crossing a literature
      review on privatization of national health services with a literature review on
      the comparative performance of non-profit and for-profit healthcare
      organizations, this paper assesses the impact of contracting private non-profit
      healthcare organizations on the efficiency, quality and responsiveness of
      services, in public universal health care systems. The results of the review were
      then compared to the existing evidence on the Portuguese hospital devolution to
      NPO program. The evidence in this paper suggests that NHS health system reforms
      that transfer some public-sector hospitals to NPO should deliver improvements to
      the health system with minimal downside risks. The very limited existing evidence
      on the Portuguese hospital devolution program suggests it improved efficiency and
      access, without sacrificing quality.

PMID- 28433326
TI  - Status of the development of a vaccine against Mycoplasma bovis.
AB  - Mycoplasma bovis is an important pathogen of cattle and, despite numerous efforts
      an effective vaccine for control of the disease it causes remains elusive.
      Although we now know more about the biology of this pathogen, information is
      lacking about appropriate protective antigens, the type of immune response that
      confers protection and adjuvants selection. The use of conserved recombinant
      proteins, selected using in silico approaches, as components of a vaccine may be
      a better choice over bacterin-based vaccines due to the limited protection
      afforded by them and adverse reactions caused by them. More studies are needed on
      the characterization of host-pathogen interactions and to elucidate M. bovis
      products modulating these interactions. These products could be the basis for
      development of vaccines to control M. bovis infections in dairy farms and
      feedlots.

PMID- 28433327
TI  - Replacing antibodies with modified DNA aptamers in vaccine potency assays.
AB  - Vaccine in vitro potency assays are vital regulatory tests that are used to
      confirm the presence and concentration of an antigen of interest in a form that
      directly or indirectly relates to protective activity in patients. Current assays
      come in many forms, but they almost exclusively use antibody reagents for
      selective detection of the target antigen. Antibodies provide specific
      recognition of vaccine antigens but also exhibit drawbacks such as stability
      limitations, cost, and lot-to-lot variation, which can make it challenging to
      maintain the reagent throughout the lifetime of the vaccine. We explored
      replacing antibodies with aptamers. Aptamers are macromolecules, such as nucleic
      acids, which can bind to their targets with high specificity and affinity,
      similar to that of antibodies. Some of the advantages of using aptamers over
      antibodies is that aptamers can be more stable, smaller, less expensive to
      produce, synthesized in vitro, and logistically easier to supply throughout the
      multi-decade lifespan of a commercial vaccine. We created modified DNA aptamers
      against the common vaccine carrier protein, CRM197. Several aptamers were
      discovered and one was chosen for further characterization. The binding kinetics
      of the aptamer revealed an off-rate 16-fold slower than anti-CRM197 antibodies
      used for comparison. The aptamers were more sensitive than available antibodies
      in some assay formats and comparable in others. The aptamer epitope was mapped to
      the receptor-binding domain of CRM197, a site adjacent to a known antibody
      binding site. These data address some key aspects for a path forward in replacing
      antibodies with aptamers for use as critical reagents in vaccine assays. We
      further highlight the possibility of using nucleic acid reagents to develop next
      generation potency assays.

PMID- 28433328
TI  - Role of non-traditional locations for seasonal flu vaccination: Empirical
      evidence and evaluation.
AB  - This study investigated the role of non-traditional locations in the decision to
      vaccinate for seasonal flu. We measured individuals' preferred location for
      seasonal flu vaccination by examining the National H1N1 Flu Survey (NHFS)
      conducted from late 2009 to early 2010. Our econometric model estimated the
      probabilities of possible choices by varying individual characteristics, and
      predicted the way in which the probabilities are expected to change given the
      specific covariates of interest. From this estimation, we observed that non
      traditional locations significantly influenced the vaccination of certain
      individuals, such as those who are high-income, educated, White, employed, and
      living in a metropolitan statistical area (MSA), by increasing the coverage.
      Thus, based on the empirical evidence, our study suggested that supporting non
      traditional locations for vaccination could be effective in increasing
      vaccination coverage.

PMID- 28433329
TI  - Measles epidemics and seroepidemiology of population in Wujin, Changzhou city,
      Jiangsu province, China 2015.
AB  - The measles epidemic was rather severe in Wujin 2015, and a seroprevalence survey
      of measles antibody was conducted during June to September 2015 in Wjin district
      of Changzhou city. Blood samples were collected from community health population
      and convenient samples of residual blood from hospitals. Measles-specific IgG
      levels were measured by ELISA assay. A total of 122 measles cases were reported
      2015 in Wujin district with an incidence of 8.31 per 100000 populations. A large
      proportion of measles cases were adults >=20years (62.30%) and infants aged
      <18months (28.69%). Floating population accounted for 68.57% of all cases. 1070
      blood samples aged from 9months to 49years old were collected and the overall
      seroprevalence and geometric mean titer (GMT) of measles were 82.71% and
      551.19mIU/ml, respectively. Although the seroprevalence among children aged
      9months to 4years was consistently over 90%, it began to decrease since 24months,
      and till the age of >=10years, the seroprevalences were all <80%, however, the
      seroprevalence rised to above 80% in people over 40years. There were no
      significant differences between the two blood sample sources in the level of
      seroprevalence and GMT. Also no significant differences were observed in the
      seroprevalence of measles and GMT levels between genders. The seroprevalence and
      GMT in people with measles vaccination were higher than those without measles
      vaccination or people whose measles vaccination are unknown (P<0.001). Our study
      indicated that the adult measles cases have become a serious problem in Wujin
      district, which may mainly relate to the increasing size of the floating
      population with low measles vaccine coverage. The seroprevalence of measles
      decreased dramatically with increasing age since teenagers, which may mainly
      caused by waning vaccine-induced immunity. Therefore, it is necessary to
      strengthen measles vaccine in these people especially floating population.

PMID- 28433330
TI  - Bivalent rLP2086 (Trumenba(r)): Development of a well-characterized vaccine
      through commercialization.
AB  - The phrase "Process is the Product" is often applied to biologics, including
      multicomponent vaccines composed of complex components that evade complete
      characterization. Vaccine production processes must be defined and locked early
      in the development cycle to ensure consistent quality of the vaccine throughout
      scale-up, clinical studies, and commercialization. This approach of front-loading
      the development work helped facilitate the accelerated approval of the Biologic
      License Application for the well-characterized vaccine bivalent rLP2086
      (Trumenba(r), Pfizer Inc) in 2014 under Breakthrough Therapy Designation.
      Bivalent rLP2086 contains two rLP2086 antigens and is licensed for the prevention
      of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B
      in individuals 10-25years of age in the United States. This paper discusses the
      development of the manufacturing process of the two antigens for the purpose of
      making it amenable to any manufacturing facility. For the journey to
      commercialization, the operating model used to manage this highly accelerated
      program led to a framework that ensured "right the first time" execution, robust
      process characterization, and proactive process monitoring. This framework
      enabled quick problem identification and proactive resolutions, resulting in a
      robust control strategy for the commercial process.

PMID- 28433331
TI  - [Decrease in the incidence of chickenpox in the Community of Madrid after
      universal childhood immunization. Years 2001-2015].
AB  - OBJECTIVE: Varicella vaccine was recommended in the Community of Madrid (CM) at
      15months of age between November 2006 and December 2013. The objective was to
      describe the impact of vaccination on the incidence of varicella in the CM during
      the period 2001-2015. DESIGN: A descriptive study of cases of varicella reported
      to the Sentinel Physician Network of the CM and the cases recorded in the Minimum
      Basic Data Set at hospital discharge was carried out. Total incidence of cases
      and of hospital admissions were calculated, as well as specific incidence by age
      and sex. RESULTS: The incidence was 94.0% lower between 2012 and 2013 than
      between 2001 and 2003. Between 2014 and 2015 the incidence was 61.8% higher than
      between 2012 and 2013. The highest incidence was observed in children aged 0 to
      4years except for 2010-2014, which was exceeded by the incidence in children aged
      5 to 9. The trend in hospital admissions was also decreasing, with the highest
      incidence in children aged 0 to 1year, followed by 1-4years. CONCLUSIONS: There
      has been a significant decrease in the incidence of cases and of hospital
      admissions by varicella in all age groups after the recommendation to vaccinate
      at 15months of age, which is compatible with the effectiveness of a dose and its
      ability to produce immunity group. The withdrawal of this recommendation between
      2014 and 2015 has led to an increase in the incidence.

PMID- 28433332
TI  - Cardiovascular outcomes in patients with peripheral arterial disease as an
      initial or subsequent manifestation of atherosclerotic disease: Results from a
      Swedish nationwide study.
AB  - OBJECTIVE: Long-term progression of peripheral arterial disease (PAD) as initial
      manifestation of atherosclerotic arterial disease is not well described.
      Cardiovascular (CV) risk was examined in different PAD populations diagnosed in a
      hospital setting in Sweden. METHODS: Data for this retrospective cohort study
      were retrieved by linking data on morbidity, medication use, and mortality from
      Swedish national registries. Primary CV outcome was a composite of myocardial
      infarction, ischemic stroke (IS), and CV death. Kaplan-Meier analysis and Cox
      proportional hazards modeling was used for describing risk and relative risk.
      RESULTS: Of 66,189 patients with an incident PAD diagnosis (2006-2013), 40,136
      had primary PAD, 16,786 had PAD + coronary heart disease (CHD), 5803 had PAD +
      IS, and 3464 had PAD + IS + CHD. One-year cumulative incidence rates of major CV
      events for the groups were 12%, 21%, 29%, and 34%, respectively. Corresponding
      numbers for 1-year all-cause death were 16%, 22%, 33%, and 35%. Compared with the
      primary PAD population, the relative risk increase for CV events was highest in
      patients with PAD + IS + CHD (hazard ratio [HR], 2.01), followed by PAD + IS (HR,
      1.87) and PAD + CHD (HR, 1.42). Despite being younger, the primary PAD population
      was less intensively treated with secondary preventive drug therapy. CONCLUSIONS:
      PAD as initial manifestation of atherosclerotic disease diagnosed in a hospital
      based setting conferred a high risk: one in eight patients experienced a major CV
      event and one in six patients died within 1 year. Despite younger age and
      substantial risk of future major CV events, patients with primary PAD received
      less intensive secondary preventive drug therapy.

PMID- 28433333
TI  - Effects of hospital safety-net burden and hospital volume on failure to rescue
      after open abdominal aortic surgery.
AB  - OBJECTIVE: Failure to rescue (FTR) is defined as the inability to rescue a
      patient from major perioperative complications, resulting in operative mortality.
      FTR is a known contributor to operative mortality after open abdominal aortic
      surgery. Understanding the causes of FTR is essential to designing interventions
      to improve perioperative outcomes. The objective of this study was to determine
      the relative contributions of hospital volume and safety-net burden (the
      proportion of uninsured and Medicaid-insured patients) to FTR. METHODS: The
      Nationwide Inpatient Sample (2001-2011) was analyzed to investigate variables
      associated with FTR after elective open abdominal aortic operations in the United
      States. FTR was defined as in-hospital death following postoperative
      complications. Mixed multivariate regression models were used to assess
      independent predictors of FTR, taking into account the clustered structure of the
      data (patients nested into hospitals). RESULTS: A total of 47,233 elective open
      abdominal aortic operations were performed in 1777 hospitals during the study
      period. The overall incidences of postoperative complications, in-hospital
      mortality, and FTR in the whole cohort were 32.7%, 3.2%, and 8.6%, respectively.
      After adjusting for demographics, comorbidities, and hospital characteristics,
      safety-net burden was significantly associated with increased likelihood of FTR
      (highest vs lowest quartile of safety-net burden, odds ratio, 1.59; 95%
      confidence interval, 1.32-1.91; P < .0001). In contrast, after adjusting for
      safety-net burden, procedure-specific hospital volume was not significantly
      associated with FTR (P = .897). CONCLUSIONS: After adjusting for patient- and
      hospital-level variables, including hospital volume, safety-net burden was an
      independent predictor of FTR after open aortic surgery. Future investigations
      should be aimed at better understanding the relationship between safety-net
      hospital burden and FTR to design interventions to improve outcomes after open
      abdominal aortic surgery.

PMID- 28433335
TI  - Treatment of peripheral arterial disease via percutaneous brachial artery access.
AB  - OBJECTIVE: This review was conducted to evaluate the types of endovascular
      procedures that can be performed via brachial artery access, evaluate the access
      success rate, and determine the incidence of technical complications. METHODS: A
      retrospective 10-year record review at a tertiary facility from January 1, 2005,
      through June 30, 2015, was completed. Patients who underwent attempted brachial
      artery access were eligible for review. Outcomes intended to be evaluated
      included ability to access the vessel, reach an identified lesion, and perform an
      indicated procedure, while describing the incidence and type of complications
      that occurred to clarify the utility and safety of brachial artery access.
      RESULTS: The review included 265 access cases in 179 patients. The access success
      rate was 98.9%. Intervention was performed in 223 cases (84.2%). Angioplasty was
      the most common intervention (59%, [154 cases]), with stents, atherectomy,
      coiling, and percutaneous thrombectomy having also been performed. Complications
      included hematoma (2.3%) and pseudoaneurysm (1.5%). Complications requiring
      intervention occurred in 1.9% of procedures. Interventions were performed on all
      major vessels as distal as the dorsalis pedis. Sheath sizes ranged from 4F to 7F.
      Intervention was performed on bilateral lower extremities in 38 cases (14.5%). A
      femoral bypass graft was present in 141 patients (53%) as the main indication for
      brachial artery access. CONCLUSIONS: Brachial access is a reliable and effective
      option for treatment of peripheral vascular disease and should be considered when
      femoral access is difficult or contraindicated and when a bypass graft is present
      in the femoral region. In addition, bilateral lesions may be approached easily
      through one brachial artery access site, making this approach advantageous when
      bilateral lesions are expected. The complication rate is similar to femoral
      access and can be minimized with ultrasound-guided access distally over the
      humerus, micropuncture access, and a dedicated postprocedure "hold team."

PMID- 28433334
TI  - A reflection on the closing of a chapter in the history of American vascular
      surgery.

PMID- 28433336
TI  - The association of postoperative glycemic control and lower extremity procedure
      outcomes.
AB  - OBJECTIVE: The effect of postoperative hyperglycemia in patients undergoing open
      and endovascular procedures on the lower extremities has not been fully
      characterized with regard to associated admission diagnoses, hospital
      complications, mortality, and 30-day readmission. This study evaluated the
      relationship of postoperative hyperglycemia on outcomes after lower extremity
      vascular procedures for peripheral artery disease. METHODS: Patients with
      peripheral artery disease admitted for elective lower extremity procedures
      between September 2008 and March 2014 were selected from the Cerner Health Facts
      (Cerner Corporation, Kansas City, Mo) database using International Classification
      of Diseases, Ninth Edition, Clinical Modification diagnosis and procedure codes.
      Using chi2 analysis, we evaluated the relationship of postoperative hyperglycemia
      (>180 mg/dL) with sociodemographic characteristics, acute and chronic diagnoses,
      infections, hospital length of stay (LOS), and 30-day readmission. An adjusted
      multivariable logistic model was used to examine the association of postoperative
      hyperglycemia with infection and LOS. RESULTS: Of 3586 patients in the study,
      2812 (78%) had optimal postoperative glucose control, and 774 (22%) had
      suboptimal glucose control (hyperglycemia). On average, patients with
      postoperative hyperglycemia experienced longer hospital stays (6.9 vs 5.1 days; P
      < .0001), higher Charlson Comorbidity Index scores (3.4 vs 2.5, P < .0001),
      higher rates of infection (23% vs 14%, P < .0001), more acute complications (ie,
      fluid and electrolyte disorders, acute renal failure, postoperative respiratory
      complications), and chronic problems (ie, anemia, chronic heart disease, chronic
      kidney disease, and diabetes) than patients with optimal glucose control. Overall
      30-day readmission was 10.9% and was similar between the groups (10.9% for both;
      P = .93). Major amputations did not differ between groups (P = .21). After
      adjusting for other risk factors using multivariable logistic regression,
      patients with hyperglycemia have 1.3-times the odds to have an infectious
      complication compared with those with optimal glucose control (odds ratio [OR],
      1.34; 95% confidence interval [CI], 1.06-1.69) and 1.7-times the odds to have a
      hospital LOS >10 days (OR, 1.69; 95% CI, 1.32-2.15). As well, patients with
      postoperative hyperglycemia have 8.4-times the odds of dying in the hospital (OR,
      8.40; 95% CI, 3.95-17.9). CONCLUSIONS: One in five patients undergoing vascular
      procedures had postoperative hyperglycemia. Postoperative hyperglycemia was
      associated with adverse events after lower extremity vascular procedures in
      patients with and without diabetes, including infection, increased hospital
      utilization, and mortality. No difference was found with respect to hospital
      readmission. Postprocedure glucose management may represent an important quality
      marker for improving outcomes after lower extremity vascular procedures.

PMID- 28433337
TI  - Increased resource utilization and overall morbidity are associated with general
      versus regional anesthesia for carotid endarterectomy in data collected by the
      Michigan Surgical Quality Collaborative.
AB  - OBJECTIVE: Advocates for performing carotid endarterectomy (CEA) under regional
      anesthesia (RA) cite reduction in hemodynamic instability and the ability for
      neurologic monitoring, but many still prefer general anesthesia (GA) as benefits
      of RA have not been clearly demonstrated, reliable RA may not be available in all
      centers, and a certain amount of movement by the patient during the procedure may
      not be uniformly tolerated. We evaluated the association of anesthesia type and
      perioperative morbidity and mortality as well as resource utilization in patients
      undergoing CEA using the Michigan Surgical Quality Collaborative (MSQC) database.
      METHODS: Between 2012 and 2014, 4558 patients underwent CEA among the MSQC
      participating hospitals. Of these patients, 4008 underwent CEA under GA and 550
      underwent CEA under RA. Data points were collected for each procedure, and a
      review of 30-day perioperative outcomes was conducted using the chi2 test.
      Propensity score regression adjusted for case mix preoperative conditions as
      fixed effects, and a mixed model adjusted for site as a random effect. RESULTS:
      The two groups were similar in gender and incidence of hypertension, diabetes,
      congestive heart failure, and smoking history. The RA group tended to be of
      better functional status. After GA, there was a greater than twofold higher
      percentage of any morbidity (8.7% vs 4.2%). Further analysis demonstrated that
      patients undergoing GA had higher unadjusted rates for mortality (1.0% vs 0.0%),
      unplanned intubations (2.1% vs 0.6%), pneumonia (1.3% vs 0.0%), sepsis (0.8% vs
      0.0%), and readmissions (9.2% vs 6.1%). Adjusting for case mix and random effect,
      there was statistically significantly higher overall morbidity (P = .0002),
      unplanned intubation (P = .0196), extended length of stay (P = .0007), emergency
      department visits (P = .0379), and readmissions (P = .0149) in the GA group.
      There was no statistically significant difference in incidence of myocardial
      infarction or cerebrovascular accident. CONCLUSIONS: Based on this analysis from
      the MSQC database, there is an associated increased morbidity and resource
      utilization with GA vs RA for CEA. This has implications for enterprise resource
      planning initiatives and the CEA value proposition in general, which is of
      special interest to both hospitals and payers.

PMID- 28433338
TI  - Morbidity of endovascular abdominal aortic aneurysm repair is directly related to
      diameter.
AB  - OBJECTIVE: Previous randomized controlled trials have defined specific size
      thresholds to guide surgical decision-making in patients presenting with an
      abdominal aortic aneurysm (AAA). With recent advances in endovascular techniques,
      the anatomic considerations of AAA repair are rapidly changing. Our specific aims
      were to evaluate the most recent national population data to compare anatomic
      differences and perioperative outcomes in patients with AAA. METHODS: The
      American College of Surgeons National Surgical Quality Improvement Program was
      queried from 2011 to 2015 using the targeted vascular public use file. Patients
      with AAA undergoing elective open or endovascular repair were included. Risk
      factors and outcomes were stratified by size and divided into quartiles for
      categorical comparison. A logistic regression model was used to compare the
      impact of size on morbidity and mortality with each technique. A risk adjustment
      model used all preoperative criteria to generate observed and expected values for
      open and endovascular repair. RESULTS: There were 10,026 patients who underwent
      elective AAA repair, 8182 (81.6%) endovascular and 1844 (18.4%) open. Repairs
      were divided into density quartiles for a logistic analysis: smallest quartile,
      3.5 to 5 cm; second quartile, 5.01 to 5.5 cm; third quartile, 5.51 to 6.2 cm; and
      largest quartile, >6.2 cm. Patients with larger aneurysms (>6.2 cm) were more
      likely to be male, to have a dependent functional status, and to have increased
      blood urea nitrogen concentration and American Society of Anesthesiologists score
      (P < .05). Larger aneurysms had longer operative time (162 vs 135 minutes) and
      greater extension toward the renal and iliac vessels (all P < .05). Risk
      adjustment revealed an observed/expected morbidity plot that favored endovascular
      repair throughout the size range but confirmed lack of size effect within the
      open repair category. The adjusted increase in morbidity with endovascular repair
      is 9.7% per centimeter increase in size of AAA. These trends remained true with
      an infrarenal subgroup analysis. CONCLUSIONS: Patients with a larger AAA have
      comorbidities and anatomic factors associated with a more difficult repair. The
      higher morbidity seen with larger aneurysms represents both anatomic and patient
      factors but seems to have a greater impact on endovascular repairs. However,
      endovascular repair still results in fewer near-term complications than open
      repair across all size strata.

PMID- 28433339
TI  - A prospective randomized comparison of contralateral snare versus retrograde gate
      cannulation in endovascular aneurysm repair.
AB  - OBJECTIVE: The objective of this study was to compare snare vs the standard
      retrograde gate cannulation method during endovascular aneurysm repair to
      determine the most efficient technique and to evaluate whether time was affected
      by graft design or the surgeon's experience. METHODS: This was a prospective
      randomized study involving single-center elective endovascular aneurysm repairs.
      Patients were randomized to the snare or retrograde group in a 1:1 ratio. The
      initial method was attempted for 15 minutes; if it was unsuccessful, the team
      switched to the alternative technique for an additional 15 minutes. The protocol
      continued until success was achieved. Data collected on demographic, anatomic,
      and procedural factors were analyzed for statistically significant differences.
      RESULTS: A total of 101 patients were included. Average age was 75.3 years, and
      82% were male; 49 patients were randomized to snare and 52 to retrograde
      cannulation. The groups were overall similar. Median cannulation times were 3.9
      minutes for the snare and 2.7 minutes for the retrograde technique (P = .13). The
      snare group attempts were successful within the initial 15-minute period in all
      but one patient (98% success). In the retrograde group, 5 of the 52 (10%) crossed
      over to snare. This difference did not reach statistical significance (P = .11).
      A difference was seen in the extremes of cannulation times. The surgeon's
      experience and graft design were not found to have significant effects on
      cannulation times. Further analysis of the retrograde group patients with long
      cannulation time found a relative breakpoint at the 5-minute mark. In those
      exceeding this time mark, the chance of eventual cannulation within 15 minutes
      dropped to 67%. In this group, median time to cannulation was 12.2 minutes for
      retrograde compared with 7.1 minutes for snare after crossover. CONCLUSIONS: Gate
      cannulation was successful using both methods with no statistical difference
      between the two in median time. Retrograde cannulation was found to be more
      likely to have short times. If cannulation by retrograde technique had not been
      achieved in the first 5 minutes, the chances of eventual success dropped
      significantly, and crossover to snare was more efficient. This finding suggests
      that one should consider an alternative method of gate cannulation if it has not
      been accomplished within this time.

PMID- 28433340
TI  - Caregiver stress among inner-city school children with asthma.

PMID- 28433341
TI  - Thiocolchicoside: An unusual suspect of drug hypersensitivity.

PMID- 28433342
TI  - Could we compare two totally different groups of patients without adjustment?

PMID- 28433343
TI  - Guidelines for type 2 diabetes: keeping a finger on the pulse.

PMID- 28433344
TI  - Application of a rapid HILIC-UV method for synthesis optimization and stability
      studies of immunogenic neo-glycoconjugates.
AB  - Proteins and glycoproteins with therapeutic activity are susceptible to
      environmental factors, which can cause their degradation and the loss of their
      activity. Thus, the maintenance of their stability during the production process
      is a critical factor. In this work, a simple and rapid hydrophilic interaction
      liquid chromatography HILIC-UV method was validated in terms of accuracy,
      precision, linearity, LOD, LOQ and specificity and applied to the investigation
      of the stability of intact proteins and their neo-glycoconjugates with antigenic
      activity against tuberculosis. The method proved to be suitable for the
      estimation of the degradation of the proteins under critical conditions (i.e.
      freeze-thaw cycles) and for the monitoring of their coupling reaction with
      saccharidic moieties, without the need of sample preparation. In addition, the
      chromatographic analysis allowed to calculate the yields of the protein
      glycosylation reaction.

PMID- 28433345
TI  - The effect of pre-existing malnutrition on pediatric burn mortality in a sub
      Saharan African burn unit.
AB  - INTRODUCTION: Nutritional status predicts burn outcomes in the developed world,
      but its effect on burn mortality in the developing world has not been widely
      studied. In sub Saharan Africa, burn is primarily a disease of children, and the
      majority of children in sub-Saharan Africa are malnourished. We therefore sought
      to determine the prevalence and effect of malnutrition on burn mortality at our
      institution. METHODS: This is a retrospective review of children aged 0-5, with
      anthropomorphic measurements available, who were admitted to our burn unit from
      July 2011 to May 2016. Age-adjusted Z scores were calculated for height, weight,
      weight for height, and mid-upper arm circumference (MUAC). Following bivariate
      analysis, we used logistic regression to construct a fully adjusted model of
      predictors of mortality. RESULTS: Of the 1357 admitted patients, 839 (61.2%) were
      aged 0-5. Of those, 512 (62.9%) had one or more anthropomorphic measurements
      available, and were included in the analysis. 54% were male, and the median age
      was 28 months. The median TBSA was 15%, with a majority of burns caused by scalds
      (77%). Mortality was 16%. Average Z-score for any of the indicators of
      malnutrition was -1.45+/-1.66. TBSA (OR: 1.08, 95% CI: 1.06, 1.11), decreasing Z
      score (OR: 1.19, 95% CI: 1.00, 1.41), and flame burn (OR: 2.51, 95% CI: 1.40,
      4.49) were associated with an increase in mortality. CONCLUSION: Preexisting
      malnutrition in burn patients in sub-Saharan Africa increases odds of mortality
      after controlling for significant covariates. Survival of burn patients in this
      region will not reach that of the developed world until a strategy of aggressive
      nutritional support is implemented in this population.

PMID- 28433346
TI  - Biomechanical Flow Amplification Arising From the Variable Deformation of the
      Subglottic Mucosa.
AB  - OBJECTIVE: This study mapped the variation in tissue elasticity of the subglottic
      mucosa, applied these data to provide initial models of the likely deformation of
      the mucosa during the myoelastic cycle, and hypothesized as to the impact on the
      process of phonation. STUDY DESIGN: Six donor human larynges were dissected along
      the sagittal plane to expose the vocal folds and subglottic mucosa. A linear skin
      rheometer was used to apply a controlled shear force, and the resultant
      displacement was measured. These data provided a measure of the stress/strain
      characteristics of the tissue at each anatomic point. A series of measurements
      were taken at 2-mm interval inferior of the vocal folds, and the change in
      elasticity was determined. RESULTS: It was found that the elasticity of the
      mucosa in the subglottic region increased linearly with distance from the vocal
      folds in all 12 samples. A simple deformation model indicated that under low
      pressure conditions the subglottic mucosa will deform to form a cone, which could
      result in a higher velocity, thus amplifying the low pressure effect resulting
      from the Venturi principle, and could assist in maintaining laminar flow.
      CONCLUSIONS: This study indicated that the deformation of the subglottic mucosa
      could play a significant role in the delivery of a low pressure airflow over the
      vocal folds. A large scale study will now be undertaken to secure more data to
      evaluate this hypothesis, and using computational fluid dynamics based on actual
      three-dimensional structure obtained from computed tomography scans the
      aerodynamics of this region will be investigated.

PMID- 28433347
TI  - Phonological and semantic processing during comprehension in Wernicke's aphasia:
      An N400 and Phonological Mapping Negativity Study.
AB  - Comprehension impairments in Wernicke's aphasia are thought to result from a
      combination of impaired phonological and semantic processes. However, the
      relationship between these cognitive processes and language comprehension has
      only been inferred through offline neuropsychological tasks. This study used ERPs
      to investigate phonological and semantic processing during online single word
      comprehension. EEG was recorded in a group of Wernicke's aphasia n=8 and control
      participants n=10 while performing a word-picture verification task. The N400 and
      Phonological Mapping Negativity/Phonological Mismatch Negativity (PMN) event
      related potential components were investigated as an index of semantic and
      phonological processing, respectively. Individuals with Wernicke's aphasia
      displayed reduced and inconsistent N400 and PMN effects in comparison to control
      participants. Reduced N400 effects in the WA group were simulated in the control
      group by artificially degrading speech perception. Correlation analyses in the
      Wernicke's aphasia group found that PMN but not N400 amplitude was associated
      with behavioural word-picture verification performance. The results confirm
      impairments at both phonological and semantic stages of comprehension in
      Wernicke's aphasia. However, reduced N400 responses in Wernicke's aphasia are at
      least partially attributable to earlier phonological processing impairments. The
      results provide further support for the traditional model of Wernicke's aphasia
      which claims a causative link between phonological processing and language
      comprehension impairments.

PMID- 28433349
TI  - Micro-Coordination of Pacemaker Potentials in the Intestine of the Mouse.

PMID- 28433348
TI  - The influence of polyethylene bearing thickness on the tibiofemoral kinematics of
      a bicruciate retaining total knee arthroplasty.
AB  - BACKGROUND: The recently reintroduced bicruciate retaining Total Knee
      Arthroplasty (BCR TKA) is an effort to reproduce kinematics closer to the native
      knee. However, there is no data on appropriate balancing with this implant.
      Balancing is crucial and challenging as medial and lateral polyethylene (PE)
      inlays are modular, which allows for placement of different thicknesses in the
      medial and lateral compartments. This study aimed at providing a detailed
      kinematic view on balancing BCR TKA. METHODS: Seven fresh frozen cadaver legs
      were mounted in a kinematic rig that applied squatting under application of
      physiologic quadriceps and hamstring forces. Additionally, specimen laxity was
      assessed using Lachman tests and varus/valgus stress tests. Following testing on
      the native knee, a BCR TKA was implanted in each specimen and all trials were
      repeated. Using one millimeter increments, five inlay thicknesses were tested to
      simulate optimal balancing, symmetric under-, and overstuffing, valgus
      constellation, and varus constellation. RESULTS: Overall, knee kinematics
      following BCR TKA seem to be very close to the native knee. The changes as
      introduced to tibiofemoral kinematics through over- or understuffing the
      polyethylene inserts are affecting the system only to a minor degree and
      generally lack statistical significance. Reproduction of the tibial varus via PE
      Inlays did not lead to kinematics much closer to the native knee. CONCLUSIONS:
      The changes introduced to tibiofemoral kinematics by removal of the conforming
      meniscus and cartilage and replacement with a flat PE insert and femoral
      component are of more impact than different inlay sizes and their combinations
      for a BCR TKA.

PMID- 28433350
TI  - Open repair of chronic thoracic and thoracoabdominal aortic dissection using deep
      hypothermia and circulatory arrest.
AB  - BACKGROUND: Chronic dissection of the thoracic and thoracoabdominal aorta as
      sequela of a prior type A or B dissection is a challenging problem that requires
      close radiographic surveillance and prompt operative intervention in the presence
      of symptoms or aneurysm formation. Open repair of chronic thoracic and
      thoracoabdominal aortic dissection using deep hypothermia has been our preferred
      method to treat this complex pathology. The advantages of this technique include
      organ and spinal cord protection, the flexibility to extend the repair proximally
      into the arch, and the ability to limit ischemia to all vascular beds. METHODS:
      Open repair of arch by left thoracotomy and descending thoracic and
      thoracoabdominal aortic pathology using deep hypothermia was performed in 664
      patients from 1995 to 2015. A subset of this cohort had chronic thoracoabdominal
      aortic dissection (n = 196). All nonemergency cases received coronary angiography
      and echocardiography preoperatively. Significant coronary artery disease or
      severe aortic insufficiency was addressed before repair of the chronic
      dissection. In recent years, lumbar drains were placed preoperatively in the most
      extensive repairs (extents II and III). Important intercostal arteries from T8 to
      L1 were revascularized with smaller-diameter looped grafts. Multibranched grafts
      for the visceral segment have been preferred in recent years. RESULTS: Mean age
      of patients was 58 +/- 14 years. Men comprised 74% of the cohort. Aortopathy was
      confirmed in 18% of the cohort. Prior thoracic aortic repair occurred in 57% of
      patients, and prior abdominal aortic repair occurred in 14% of patients. Prior
      type A aortic dissection occurred in 44% of patients, and prior type B occurred
      in 56% of patients. Operative mortality was 3.6%, permanent spinal cord ischemia
      occurred in 2.6% of patients, permanent hemodialysis occurred in 0% of patients,
      and permanent stroke occurred in 1% of patients. Reexploration for bleeding was
      5.1%, and respiratory failure requiring tracheostomy occurred in 2.6%.
      Postoperative length of stay was 11.9 +/- 9.7 days. Reintervention for
      pseudoaneurysm or growth of a distal aneurysm was 6.9%. The 1-, 5-, and 10-year
      survivals were 93%, 79%, and 57%, respectively. CONCLUSIONS: Open repair of
      chronic thoracic and thoracoabdominal aortic dissection using deep hypothermia
      and circulatory arrest has low morbidity and mortality. The need for
      reintervention is low, and long-term survival is excellent. We believe that open
      repair continues to be the gold standard in patients who are suitable candidates
      for surgery.

PMID- 28433351
TI  - Is it time to take a new tack toward an old adversary?

PMID- 28433352
TI  - Replacement of the dissected thoracoabdominal aorta: Some like it cold.

PMID- 28433353
TI  - New nomenclature for robotic-assisted thoracic surgery also gets rid of RATS.

PMID- 28433354
TI  - Transcatheter aortic valve-in-valve implantation: Go with the flow?

PMID- 28433355
TI  - The no-touch saphenous vein graft in elderly coronary bypass patients with
      multiple comorbidities is a promising conduit to substitute the left internal
      thoracic artery.
AB  - OBJECTIVES: We investigated the patency rates of no-touch saphenous vein grafts
      anastomosed to the left anterior descending artery compared with the left
      internal thoracic artery. Further, we compared the patency of no-touch vein
      grafts to the left anterior descending artery with the patency of no-touch vein
      grafts to other coronary arteries. METHODS: Of 2635 consecutive patients
      undergoing coronary artery bypass grafting between 2003 and 2008, 168 (6.3%) were
      given at least a saphenous vein graft to the left anterior descending artery to
      avoid harvesting complications in high-risk patients or in response to a left
      internal thoracic artery injury. A total of 97 patients were consecutively
      included after informed consent. A clinical examination and computed tomography
      angiography were performed on 91 patients at a mean of 6 (4-9) years. RESULTS:
      The mean age of patients was 75.6 +/- 8.5 years. Postoperatively, 88.7% of
      patients (86/97) were free of angina. The 91 examined patients had 163 grafts
      with 286 distal anastomoses. Crude patency, according to distal anastomoses, was
      94.4% (270/286). The patency of single versus sequential no-touch vein grafts to
      the left anterior descending artery was 98% (50/51) versus 92.5% (37/40). The
      total patency rate was 95.6% (87/91), similar to the reported patency rate for
      the left internal thoracic artery. The no-touch grafts to the left anterior
      descending artery versus other coronaries had a patency of 95.6% (87/91) versus
      93.8% (183/195), a high similarity confirmed by an equivalence analysis.
      CONCLUSIONS: In elderly coronary bypass patients with multiple comorbidities, a
      no-touch saphenous vein graft is a promising substitute for the left internal
      thoracic artery.

PMID- 28433356
TI  - Aortic sinus flow stasis likely in valve-in-valve transcatheter aortic valve
      implantation.
AB  - OBJECTIVE: Valve-in-valve procedures using transcatheter aortic valves are
      increasingly performed to treat degenerated bioprosthetic surgical aortic valves
      because they are less invasive than redo aortic valve replacement. The objective
      of this study is to quantify the changes in aortic sinus blood flow dynamics
      before and after a valve-in-valve procedure to gain insight into mechanisms for
      clinical and subclinical thrombosis of leaflets. METHODS: A detailed description
      of the sinus hemodynamics for valve-in-valve implantation was performed in vitro.
      A Medtronic Hancock II (Medtronic Inc, Minneapolis, Minn) porcine bioprosthesis
      was modeled as a surgical aortic valve, and Medtronic CoreValve and Edwards
      Sapien (Edwards Lifesciences, Irvine, Calif) valves were used as the
      transcatheter aortic valves. High-resolution particle image velocimetry was used
      to compare the flow patterns from these 2 valves within both the left coronary
      and noncoronary sinuses in vitro. RESULTS: Velocity and vorticity within the
      surgical valve sinuses reached peak values of 0.7 m/s and 1000 s-1, with a 70%
      decrease in peak fluid shear stress near the aortic side of the leaflet in the
      noncoronary sinus. With the introduction of transcatheter aortic valves, peak
      velocity and vorticity were reduced to approximately 0.4 m/s and 550 s-1 and 0.58
      m/s and 653 s-1 without coronary flow and 0.60 m/s and 631 s-1 and 0.81 m/s and
      669 s-1 with coronary flow for the CoreValve and Sapien valve-in-valve
      implantations, respectively. Peak shear stress was approximately 38% higher along
      the aortic side of the coronary versus noncoronary transcatheter aortic valve
      leaflet. CONCLUSIONS: Decreased flow and shear stress in valve-in-valve
      procedures indicate a higher risk of leaflet thrombosis secondary to flow stasis,
      perhaps more so in the noncoronary sinus.

PMID- 28433357
TI  - Brain natriuretic peptide and N-terminal pro-brain natriuretic peptide confirmed
      the prognostic accuracy in pediatric cardiac surgery: Time for their inclusion in
      prediction risk models?

PMID- 28433358
TI  - Blood and the Zika virus.

PMID- 28433359
TI  - Feasibility of profound hypothermia as part of extracorporeal life support in a
      pig model.
AB  - OBJECTIVE: To investigate the feasibility of a refined aortic flush catheter and
      pump system to induce emergency preservation and resuscitation before
      extracorporeal cardiopulmonary resuscitation in a normovolemic cardiac arrest
      swine model simulating near real size/weight conditions of adults. METHODS: In
      this feasibility study, 8 female Large White breed pigs weighing 70 to 80 kg
      underwent ventricular fibrillation cardiac arrest for 15 minutes, followed by 4
      degrees C aortic flush (150 mL/kg for the brain; 50 mL/kg for the spine) via a
      new hardware ensued by resuscitation with extracorporeal cardiopulmonary
      resuscitation. RESULTS: Brain temperature was lowered from 39.9 degrees C
      (interquartile range [IQR] 39.6-40.3) to 24.0 degrees C (IQR 20.8-28.9) in 12
      minutes (IQR 11-16) with a median cooling rate of 1.3 degrees C (IQR 0.7-1.6) per
      minute. A median of 776 mL (IQR 673-840) per minute with a median pump pressure
      of 1487 mm Hg (IQR 1324-1545) were pumped to the brain. CONCLUSIONS: With the new
      hardware, we were able to cool the brain within a few minutes in a large pig
      cardiac arrest model. The exact position; the design, diameter, and length of the
      flush catheter; and the brain perfusion pressure seem to be critical to
      effectively reduce brain temperature. Redistribution of peripheral blood could
      lead to sterile inflammation again and might be avoided.

PMID- 28433360
TI  - The devil is in the detail.

PMID- 28433361
TI  - What and how to read: Staying current as a young cardiothoracic surgeon.

PMID- 28433362
TI  - Effect of preadmission bowel preparation on outcomes of elective colorectal
      procedures in young children.
AB  - BACKGROUND: The utility of mechanical bowel preparation (MBP) to minimize
      infectious complications in elective colorectal surgery is contentious. Though
      data is scarce in children, adult studies suggest a benefit to MBP when
      administered with oral antibiotics (OAB). METHODS: After IRB approval, the
      Pediatric Health Information System (PHIS) was queried for young children
      undergoing elective colon surgery from 2011 to 2014. Patients were divided into:
      no bowel preparation (Group 1), MBP (Group 2), and MBP plus OAB (Group 3).
      Statistical significance was determined using univariate and multivariate
      analysis with GEE models accounting for clustering by hospital. RESULTS: One
      thousand five hundred eighty-one patients met study criteria: 63.7% in Group 1,
      27.1% in Group 2, and 9.2% in Group 3. Surgical complication rate was higher in
      Group 1 (23.3%) compared to Groups 2 and 3 (14.2% and 15.5%; P<0.001). However,
      median length of stay was shorter in Group 1 (4, IQR 4days) compared to Group 2
      (5, IQR 3) and Group 3 (6, IQR 3) (P<0.001). 30-day readmission rates were
      similar. In multivariate analysis compared to patients in Group 1, the odds of
      surgical complications were 0.72 (95% CI 0.40-1.29, P=0.28) with MBP alone (Group
      2), 1.79 (95% CI 1.28-2.52, P=0.0008) with MBP+OAB (Group 3), and 1.13 (95% CI
      0.81-1.58, P=0.46) for the aggregate Group 2 plus 3. CONCLUSION: Utilization of
      bowel preparation in children is variable across children's hospitals nationally,
      and the benefit is unclear. Given the discrepancy with adult literature, a three
      armed pediatric-specific randomized controlled trial is warranted. LEVEL OF
      EVIDENCE: Level III treatment study - retrospective comparative study.

PMID- 28433363
TI  - The molecular impact of omega 3 fatty acids on hepatic pro-inflammatory cytokine
      signaling.
AB  - PURPOSE: Parenteral nutrition associated liver disease (PNALD) develops in a
      subset of children receiving parenteral nutrition for intestinal failure.
      OmegavenTM is an omega-3 fatty acid (Omega3FA) lipid emulsion high in
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that can lessen PNALD.
      Inflammatory cytokines (IL-1, TNF-alpha, TGF-beta) are elevated in PNALD and can
      decrease paraoxonase 1 protein expression (PON1). We sought to determine the
      effect of OmegavenTM, EPA, and DHA on inflammatory cytokines TNF-alpha, IL-1, and
      TGF-beta via ERK1/2 and p-Smad2/3 signaling pathways as well as the changes in
      intracellular PON1 protein expression as a potential mechanism explaining the
      protective effects of OmegavenTM and Omega3FA. METHODS: HepG2 cells were cultured
      with each cytokine and OmegavenTM, or EPA and DHA, or IntralipidTM. P-Smad2/3 and
      PON1 protein levels were measured by Western blotting. ERK1/2 signaling was
      studied using homogenous time resolved fluorescence. RESULTS: OmegavenTM
      decreased TGF-beta mediated Smad2/3 signaling by 30% (70% of control +/-12,
      p<0.03). OmegavenTM decreased IL-1 and TNF-alpha mediated ERK1/2 signaling (0.49
      fold +/-0.09, p<0.05 and 0.22+/-0.05, p<0.05) compared to control. CONCLUSION:
      Our results describe potential mechanisms by which OmegavenTM and Omega3FA can be
      hepatoprotective in the setting of PNALD by abating inflammatory cytokine
      signaling.

PMID- 28433364
TI  - Belts Evaluated as Limb Tourniquets: BELT Study Comparing Trouser Supporters Used
      as Medical Devices in a Manikin Model of Wound Bleeding.
AB  - OBJECTIVE: The purpose of the present study is to compare several models of
      commercially designed belts as used as a tourniquet. METHODS: In the Belts
      Evaluated as Limb Tourniquets (BELT) study, an experiment was designed to test
      the effectiveness of pants belts as nonimprovised medical devices to control
      hemorrhage in a manikin. Models of belts included Tourni-belt, Tourniquet Belt,
      ParaBelt, and Battle Buddy. Data collected included effectiveness, time to stop
      bleeding, total time of application, pressure, blood loss, and composite results
      (score count of good results; composite outcome good if every component was
      good). RESULTS: Differences in effectiveness percentages among models were not
      statistically significant. The difference in mean between users was statistically
      significant for stop time, total time, pressure, blood loss, composite score, and
      composite outcome. Mean time to stop bleeding differed for only 1 pair of models
      after the Tukey-Kramer adjustment; ParaBelt was faster than Tourniquet Belt. Mean
      total time of application differed between ParaBelt-Tourniquet Belt and Tourni
      belt-Tourniquet Belt; the former model in both pairs was faster. No significant
      difference in mean blood loss measured by model was found. For composite outcome
      score, no pairwise difference between models was significant. For composite
      outcome (good-bad), ParaBelt had good results in 75% of tests; the other 3 models
      had significantly worse results. CONCLUSIONS: In a preliminary laboratory
      analysis of belt tourniquet models using a manikin, performance differed by
      model. ParaBelt performed better than other models for the composite outcome.

PMID- 28433365
TI  - Introduction: To transfer or not transfer...a mosaic embryo, that is the
      question.
AB  - This issue's Views and Reviews section aims to offer readers a 360 degrees  view
      of the knowledge accumulated regarding the transfer of mosaic embryos by experts
      from around the world, as well as an in vitro fertilization worldwide survey on
      the topic.

PMID- 28433366
TI  - A first-choice combined oral contraceptive influences general well-being in
      healthy women: a double-blind, randomized, placebo-controlled trial.
AB  - OBJECTIVE: To determine whether there is a causal effect of oral contraceptive
      (OC) treatment on general well-being and depressed mood in healthy women. DESIGN:
      Double-blind, randomized, and placebo-controlled trial. SETTING: University
      hospital. PATIENT(S): Three hundred and forty healthy women aged 18-35 years
      randomized to treatment, of whom 332 completed the data collection at follow-up
      evaluation. INTERVENTION(S): A combined OC (150 MUg levonorgestrel and 30 MUg
      ethinylestradiol) or placebo for 3 months of treatment. MAIN OUTCOME MEASURE(S):
      Primary outcome measures: global score of Psychological General Well-Being Index
      (PGWBI) and the Beck Depression Inventory (BDI); secondary outcome measures: six
      separate dimensions of the PGWBI. RESULT(S): The OC treatment statistically
      significantly decreased general well-being compared with placebo -4.12 (95% CI, 
      7.18 to -1.06). Furthermore, OC decreased the following PGWBI dimensions compared
      with placebo: positive well-being -3.90 (95% CI, -7.78 to -0.01), self-control 
      6.63 (95% CI, -11.20 to -2.06), and vitality -6.84 (95% CI, -10.80 to -2.88). The
      effect of OC on depressive symptoms and on the PGWBI dimension depressed mood
      were not statistically significant. CONCLUSION(S): This study demonstrates a
      statistically significant reduction in general well-being by a first-choice OC in
      comparison with placebo in healthy women. We found no statistically significant
      effects on depressive symptoms. A reduction in general well-being should be of
      clinical importance.

PMID- 28433367
TI  - Abnormal implantation after fresh and frozen in vitro fertilization cycles.
AB  - OBJECTIVE: To determine whether fresh embryo transfers are at a higher risk of
      abnormal implantation compared with frozen embryo transfers while accounting for
      the embryo stage at transfer. DESIGN: Retrospective cohort study. SETTING: Not
      applicable. PATIENT(S): We used data from the Society for Assisted Reproductive
      Technologies to identify all fresh and frozen autologous IVF cycles from 2004
      2013 resulting in a positive pregnancy test. The cycles were parameterized into a
      four-level predictor of [1] fresh blastocyst transfer, [2] fresh non-blastocyst
      transfer, [3] frozen blastocyst transfer, and [4] frozen non-blastocyst transfer.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We examined a composite outcome
      of abnormal implantation, defined as biochemical pregnancy, ectopic/heterotopic
      pregnancy, and first-trimester pregnancy loss. Regression modeling was performed
      with repeated measures multivariable logistic regression, adjusted for age,
      parity, number of embryos transferred, infertility diagnosis, and calendar year
      of treatment. RESULT(S): Of 509,938 cycles analyzed, 31.8% resulted in abnormal
      implantation. Compared with a fresh blastocyst transfer, a fresh non-blastocyst
      transfer had a 22% increase risk of abnormal implantation, a frozen blastocyst
      transfer had a 36% increase risk, and a frozen non-blastocyst transfer had a 57%
      increase risk. When individual outcomes were analyzed, fresh embryo transfers had
      a lower risk of biochemical pregnancy and pregnancy loss but a higher risk for
      ectopic/heterotopic pregnancy. CONCLUSION(S): Fresh blastocyst transfers had the
      lowest overall risk of abnormal implantation but a higher risk of
      ectopic/heterotopic pregnancy. Although embryo cryopreservation is indicated in
      certain treatment cycles, elective embryo cryopreservation may not be the optimal
      strategy to adopt for all cycles.

PMID- 28433368
TI  - Chromosomal mosaicism detected during preimplantation genetic screening: results
      of a worldwide Web-based survey.
AB  - Embryonic mosaicism, the presence of more than one distinct cell line within an
      embryo, has recently become the focus of growing attention and controversy in the
      context of preimplantation genetic screening (PGS). To evaluate the extent of
      mosaic aneuploidy in clinical practice and to gain insight on the practices and
      views regarding this issue, we conducted a survey using a prospective, 20-item
      Web-based questionnaire with questions related to practices and views regarding
      mosaicism in PGS. A total of 102 in vitro fertilization (IVF) units from 32
      countries that performed 108,900 IVF cycles annually responded to the survey.
      More than half responded that embryonic mosaic aneuploidy is reported by the
      laboratory, but 31.9% stated that samples are reported as euploid or aneuploid
      only. If mosaic aneuploidy is reported, 46% stated that it was present in <=10%
      of the embryos. More than two-thirds were of the opinion that next-generation
      sequencing is required to reliably detect mosaicism. Among centers performing
      PGS, 47.9% consider embryonic mosaicism when detected in >20% of the cells, and
      nearly two-thirds believe that mosaic aneuploid embryos should be stored for
      potential therapeutic use after extensive and appropriate counseling. In summary,
      mosaicism has always existed in preimplantation embryos, and new technologies can
      now detect its presence with higher resolution. More studies are needed before
      definite conclusions can be drawn.

PMID- 28433369
TI  - Fertility preservation and refreezing of transplanted ovarian tissue-a potential
      new way of managing patients with low risk of malignant cell recurrence.
AB  - OBJECTIVE: To report the first successful refreezing of ovarian tissue recovered
      more than 3 years after transplantation in a woman previously treated for early
      stage ovarian cancer. DESIGN: Evaluation of cryopreserved and grafted ovarian
      tissue. SETTING: University hospital. PATIENT(S): A 23-year-old woman diagnosed
      with stage 1C ovarian mucinous cystadenocarcinoma. INTERVENTION(S): The patient
      underwent ovarian tissue cryopreservation for fertility preservation and
      subsequent heterotopic transplantation for fertility restoration 9 years after
      freezing. After a successful IVF twin pregnancy, grafted tissue was
      laparoscopically removed for safety reasons. The recovered tissue was refrozen.
      MAIN OUTCOME MEASURE(S): Live birth and histologic evaluation of the distribution
      of pre-antral follicle stages. RESULT(S): The previously grafted ovarian tissue
      was successfully refrozen, presenting follicular survival 4 weeks after
      xenografting. The follicular distribution in the recovered grafts showed a shift
      toward growing-stage follicles compared with the fresh tissue. The patient
      subsequently entered menopause, and histologic evaluation revealed a total of
      five follicles in two remaining grafts which had supported ovarian function a few
      months earlier. CONCLUSION(S): This is the second case of delivery following
      heterotopic grafting as well as the second case of successful transplantation of
      ovarian tissue from a patient with early-stage ovarian cancer. The recovered
      grafts showed that a lower number of functional follicles than previously
      estimated can actually support ovarian function. Removing and refreezing grafted
      tissue could be a new way of handling not only cancer patients with a risk of
      malignant cell recurrence, but also certain groups of patients with genetic
      conditions.

PMID- 28433370
TI  - Assessing the true incidence of mosaicism in preimplantation embryos.
AB  - Modern technologies applied to the field of preimplantation genetic diagnosis for
      aneuploidy screening (PGD-A) have improved the ability to identify the presence
      of mosaicism. Consequently, new questions can now be addressed regarding the
      potential impact of embryo mosaicism on diagnosis accuracy and the feasibility of
      considering mosaic embryos for transfer. The frequency of chromosomal mosaicism
      in products of conception (POCs) of early miscarriages has been reported to be
      low. Mosaic embryos with an aneuploid inner cell mass are typically lost during
      the first trimester owing to spontaneous miscarriages. Most of the mosaics in
      established pregnancies would derive from placental mosaicism or placental
      aneuploidy, and mosaic embryos with aneuploid inner cell mass should be lost
      mainly due to first-trimester spontaneous miscarriages. The well described
      clinical outcomes of live births from mosaic embryos suggest a wide spectrum of
      phenotypes, from healthy to severely impaired. Therefore, there is a need to
      balance the risks of discarding a possibly viable embryo with that of
      transferring an embryo that may ultimately have a lower implantation potential.

PMID- 28433372
TI  - Intrinsic fertility of human oocytes.
AB  - OBJECTIVE: To study the intrinsic fertility of the human oocyte. DESIGN: A large
      retrospective study of natural cycle single embryo transfer (ET) IVF cycles.
      SETTING: Private IVF clinic, university, and private hospital. PATIENT(S):
      Patients were enrolled consecutively over an 8-year period in a single ET natural
      cycle protocol. INTERVENTION(S): A total of 13,949 oocyte retrievals with natural
      IVF single ET. Software package R (version 3.2.5) was used for statistical
      calculations. MAIN OUTCOME MEASURE(S): Live baby rate per oocyte according to
      age. RESULT(S): A total of 14,185 natural cycle oocytes resulted in 1,913 live
      babies from single ET. The number of oocytes required to make one live baby in
      this large series varied with the age of the female partner. For those under 35,
      the live baby born per oocyte was 26%. For over age 42 it decreased to 1%. These
      results fit very robustly with a logistic function curve, which is at first
      steady (horizontal), followed by a linear decline after age 35 with a 10% loss
      every year until age 43, and then a flattening out (horizontal) by age 44.
      CONCLUSION(S): The intrinsic fertility per oocyte in natural cycle is far greater
      than reported in hyperstimulated cycles, varying robustly from 26% to 4% with age
      from <35 to 42 years. The curve is relatively flat until age 34, and then
      declines rapidly 10% per year thereafter.

PMID- 28433371
TI  - In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in
      advanced maternal age: a randomized, controlled study.
AB  - OBJECTIVE: To determine the clinical value of preimplantation genetic diagnosis
      for aneuploidy screening (PGD-A) in women of advanced maternal age (AMA; between
      38 and 41 years). DESIGN: This was a multicenter, randomized trial with two arms:
      a PGD-A group with blastocyst transfer, and a control group with blastocyst
      transfer without PGD-A. SETTING: Private reproductive centers. PATIENT(S): A
      total of 326 recruited patients fit the inclusion criteria, and 205 completed the
      study (100 in the PGD-A group and 105 in the control group). INTERVENTION(S): Day
      3 embryo biopsy, array comparative genomic hybridization, blastocyst transfer,
      and vitrification. MAIN OUTCOME MEASURE(S): Primary outcomes were delivery and
      live birth rates in the first transfer and cumulative outcome rates. RESULT(S):
      The PGD-A group exhibited significantly fewer ETs (68.0% vs. 90.5% for control)
      and lower miscarriage rates (2.7% vs. 39.0% for control). Delivery rate after the
      first transfer attempt was significantly higher in the PGD-A group per transfer
      (52.9% vs 24.2%) and per patient (36.0% vs. 21.9%). No significant differences
      were observed in the cumulative delivery rates per patient 6 months after closing
      the study. However, the mean number of ETs needed per live birth was lower in the
      PGD-A group compared with the control group (1.8 vs. 3.7), as was the time to
      pregnancy (7.7 vs. 14.9 weeks). CONCLUSION(S): Preimplantation genetic diagnosis
      for aneuploidy screening is superior compared with controls not only in clinical
      outcome at the first ET but also in dramatically decreasing miscarriage rates and
      shortening the time to pregnancy.

PMID- 28433374
TI  - Peritoneal fluid cytokines related to endometriosis in patients evaluated for
      infertility.
AB  - OBJECTIVE: Our aim was to characterize peritoneal cytokine profiles in patients
      with infertility, with and without endometriosis, to illuminate potential
      differences in immune profiles that may reflect mechanistic differences between
      these two patient populations. DESIGN: Cross-sectional study. SETTING: University
      hospital and research center. PATIENT(S): Women undergoing laparoscopy for
      infertility investigation (n = 107). INTERVENTION(S): Peritoneal fluid was
      collected during surgery. Clinical characteristics were registered
      preoperatively. MAIN OUTCOME MEASURE(S): We determined the concentration of 48
      different cytokines from the peritoneal fluid with multiplex immunoassays.
      Associations between cytokines and clinical findings were assessed with logistic
      regression and partial least squares discriminant analyses (PLS-DA). RESULT(S):
      Concentrations of SCGF-beta, IL-8, HGF, and MCP-1 were significantly higher,
      while IL-13 was significantly lower in the endometriosis group compared with the
      group without endometriosis. Multiple stepwise logistic regression identified a
      combination of SCGF-beta, IL-13, and G-CSF concentrations that predicted the
      presence of endometriosis with 86% sensitivity and 67% specificity. PLS-DA
      identified a class of 11 cytokines (SCGF-beta, HGF, IL-13, MCP-1, CTACK, MCP-3, M
      CSF, LIF, IL-5, IL-9, and IFN-a2) that were more characteristic of endometriosis
      than nonendometriosis patients. CONCLUSION(S): By combining univariate and
      multivariate analyses, profiles of cytokines more likely to be enriched or
      depleted in infertility patients with endometriosis compared with those without
      endometriosis were identified. These findings may inform future analyses of
      pathophysiological mechanisms of endometriosis in infertile patients, including
      dysregulated Th1/Th2 response and mobilization and proliferation of hematopoietic
      stem cells.

PMID- 28433373
TI  - Preimplantation genetic diagnosis for aneuploidy testing in women older than 44
      years: a multicenter experience.
AB  - OBJECTIVE: To report laboratory and clinical outcomes in preimplantation genetic
      diagnosis for aneuploidies (PGD-A) cycles for women 44 to 47 years old. DESIGN:
      Multicenter, longitudinal, observational study. SETTING: In vitro fertilization
      (IVF) centers. PATIENT(S): One hundred and thirty-seven women aged 44.7 +/- 0.7
      years (range: 44.0-46.7) undergoing 150 PGD-A cycles during April 2013 to January
      2016. INTERVENTION(S): Quantitative polymerase chain reaction-based PGD-A on
      trophectoderm biopsies and cryopreserved euploid single-embryo transfer (SET).
      MAIN OUTCOMES MEASURE(S): Primary outcome measure: delivery rate per cycle;
      secondary outcome measures: miscarriage rate, and the rate and reasons for cycle
      cancelation with subanalyses for female age and number of metaphase 2 oocytes
      retrieved. RESULT(S): In 102 (68.0%) of 150 cycles blastocyst development was
      obtained, but only 21 (14.0%) were euploid blastocysts. The overall euploidy rate
      was 11.8% (22 of 187). Twenty-one SET procedures were performed, resulting in 13
      clinical pregnancies, of which 1 miscarried and 12 delivered. The delivery rate
      was 57.1% per transfer, 8.0% per cycle, and 8.8% per patient. The logistic
      regression analysis found that only female age (odds ratio 0.78) and number of
      metaphase 2 oocytes retrieved (odds ratio 1.25) statistically significantly
      correlated with the likelihood of delivery. The delivery rate per cycle was 10.6%
      (11 of 104) in patients aged 44.0 to 44.9 years and 2.6% in patients aged 45.0 to
      45.9 years (n = 1 of 38). No euploid blastocysts were found for patients older
      than 45.0 years. CONCLUSION(S): Extensive counseling based on biological and
      clinical data should be provided to women older than 43 years who are requesting
      IVF because of their very low odds of success and high risk for embryonic
      aneuploidies. Nevertheless, the low miscarriage and good delivery rates reported
      in this study in women with good ovarian reserve aged 44 should encourage the use
      of PGD-A in this population.

PMID- 28433375
TI  - Mosaicism between trophectoderm and inner cell mass.
AB  - Defining the actual incidence and prevalence of mosaicism in human blastocysts
      still remains a difficult task. The small amount of evidence generated by animal
      and human studies does not support the existence of mechanisms involved in
      developmental arrest, clonal depletion, or aneuploidy rescue for abnormal cells
      in euploid/aneuploid embryos during preimplantation development. However, studies
      in humans are mainly descriptive and lack functional evidence. Understanding the
      biological mechanisms that beset preimplantation differentiation holds the
      potential to reveal the role of aneuploidies and gene dosage imbalances in cell
      fate decision, providing important clues on the origin and evolution of embryonic
      mosaicism. The evidence on human blastocysts suggests that a mosaic
      euploid/aneuploid configuration is detected in around 5% of embryos. This figure
      supports the extremely low level of mosaicism reported in natural and IVF
      pregnancies. Similarly, the clinical management of patterns consistent with the
      presence of mosaicism in a trophectoderm biopsy during preimplantation genetic
      diagnosis cycles (PGD-A) is still a controversial issue. Despite the facts that
      some contemporary comprehensive chromosomal screening platforms can detect mosaic
      samples in cell mixture models with variable accuracy and many reproductive
      genetics laboratories are now routinely including embryonic mosaicism on their
      genetic reports, a diagnosis of certainty for mosaicism in PGD-A cycles is
      conceptually impracticable. Indeed, several technical and biological sources of
      errors clearly exist when trying to estimate mosaicism from a single
      trophectoderm biopsy in PGD-A cycles and must be understood to adequately guide
      patients during clinical care.

PMID- 28433376
TI  - Is a Normal Testosterone Level Necessary for Erectile Function?

PMID- 28433377
TI  - Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer: Are Things Now
      Getting Personal?

PMID- 28433378
TI  - Prostate Cancer Management in an Ageing Population.

PMID- 28433379
TI  - Re: Richard J. Sylvester, Steven E. Canfield, Thomas B.L. Lam, et al. Conflict of
      Evidence: Resolving Discrepancies When Findings from Randomized Controlled Trials
      and Meta-analyses Disagree. Eur Urol 2017;71:811-9.

PMID- 28433380
TI  - Author Reply.

PMID- 28433381
TI  - Editorial Comment.

PMID- 28433382
TI  - Applications of the CRISPR-Cas9 system in kidney research.
AB  - The recently discovered clustered regularly interspaced short palindromic repeat
      (CRISPR)-CRISPR-associated protein 9 (Cas9) is an RNA-guided DNA nuclease, and
      has been harnessed for the development of simple, efficient, and relatively
      inexpensive technologies to precisely manipulate the genomic information in
      virtually all cell types and organisms. The CRIPSR-Cas9 systems have already been
      effectively used to disrupt multiple genes simultaneously, create conditional
      alleles, and generate reporter proteins, even in vivo. The ability of Cas9 to
      target a specific genomic region has also been exploited for various
      applications, such as transcriptional regulation, epigenetic control, and
      chromosome labeling. Here we first describe the molecular mechanism of the RNA
      guided DNA targeting by the CRISPR-Cas9 system and then outline the current
      applications of this system as a genome-editing tool in mice and other species,
      to better model and study human diseases. We also discuss the practical and
      potential uses of the CRISPR-Cas9 system in kidney research and highlight the
      further applications of this technology beyond genome editing. Undoubtedly, the
      CRISPR-Cas9 system holds enormous potential for revolutionizing and accelerating
      kidney research and therapeutic applications in the future.

PMID- 28433384
TI  - Cold ischemia time up to 16 hours has little impact on living donor kidney
      transplant outcomes in the era of kidney paired donation.
AB  - In living donor transplantation, cold ischemia time is a concern in transplants
      involving kidney paired donation. The impact of cold ischemia time over eight
      hours is unknown. Here we examined the association of cold ischemia time with
      delayed graft function and allograft loss among 48,498 living recipients in the
      Scientific Registry of Transplant Recipients registry. The incidence of delayed
      graft function was low but significantly higher among patients with longer cold
      ischemia times (0-2.0 hours: 3.3%; 2.1-4.0 hours: 3.9%; 4.1-8.0 hours: 4.3%; 8.1
      16.0 hours: 5.5%). In multivariate analyses, only those with cold ischemia times
      of 8.1-16.0 hours had increased odds of delayed graft function (odds ratio 1.47;
      95% confidence interval 1.05-2.05) compared to patients with times of 0-2.0
      hours. In multivariate time-to-event analyses, cold ischemia times of 16 hours or
      less were not associated with allograft loss from any cause including death or
      death-censored graft loss with hazard ratios for cold ischemia times between 8.0
      16.0 hours of 0.97 (95% confidence interval 0.74-1.26) and 1.09 (0.81-1.48)
      compared to patients with times of 0-2.0 hours). The results were consistent in
      paired and non-kidney paired donation transplants and in those with living donors
      over 50 years of age. In subgroup analysis restricted to kidney paired donation
      recipients, there was no difference in the risk of delayed graft function with an
      odds ratio of 1.40 (0.88, 2.40) or all-cause graft loss with a hazard ratio of
      0.89 (0.62, 1.30) in transplant recipients who received kidneys that were shipped
      versus not shipped. Thus, a cold ischemia time up to 16 hours has limited impact
      on living donor outcomes. These findings may help expand living donor
      transplantation through kidney paired donation.

PMID- 28433383
TI  - Screening for chronic kidney disease in Canadian indigenous peoples is cost
      effective.
AB  - Canadian indigenous (First Nations) have rates of kidney failure that are 2- to 4
      fold higher than the non-indigenous general Canadian population. As such, a
      strategy of targeted screening and treatment for CKD may be cost-effective in
      this population. Our objective was to assess the cost utility of screening and
      subsequent treatment for CKD in rural Canadian indigenous adults by both
      estimated glomerular filtration rate and the urine albumin-to-creatinine ratio. A
      decision analytic Markov model was constructed comparing the screening and
      treatment strategy to usual care. Primary outcomes were presented as incremental
      cost-effectiveness ratios (ICERs) presented as a cost per quality-adjusted life
      year (QALY). Screening for CKD was associated with an ICER of $23,700/QALY in
      comparison to usual care. Restricting the model to screening in communities
      accessed only by air travel (CKD prevalence 34.4%), this ratio fell to
      $7,790/QALY. In road accessible communities (CKD prevalence 17.6%) the ICER was
      $52,480/QALY. The model was robust to changes in influential variables when
      tested in univariate sensitivity analyses. Probabilistic sensitivity analysis
      found 72% of simulations to be cost-effective at a $50,000/QALY threshold and 93%
      of simulations to be cost-effective at a $100,000/QALY threshold. Thus, targeted
      screening and treatment for CKD using point-of-care testing equipment in rural
      Canadian indigenous populations is cost-effective, particularly in remote air
      access-only communities with the highest risk of CKD and kidney failure.
      Evaluation of targeted screening initiatives with cluster randomized controlled
      trials and integration of screening into routine clinical visits in communities
      with the highest risk is recommended.

PMID- 28433386
TI  - Bilateral Fusiform Aneurysms of the Internal Carotid Arteries Presenting with
      Subarachnoid Hemorrhage.
AB  - Fusiform aneurysms of cerebral arteries are less prevalent than saccular
      aneurysms and are rarely associated with subarachnoid hemorrhage (SAH). In this
      article, we report SAH due to a rare case of bilateral fusiform aneurysm of the
      supraclinoid segment of the internal carotid arteries (ICAs) (C4 segment of the
      ICA).

PMID- 28433385
TI  - Perioperative risks of narcolepsy in patients undergoing general anesthesia: A
      case-control study.
AB  - STUDY OBJECTIVE: To compare the perioperative outcomes between patients with
      narcolepsy and matched controls undergoing anesthetic management. DESIGN:
      Retrospective 2:1 matched study design. SETTING: Large tertiary medical center.
      PATIENTS: Narcoleptic patients who underwent general anesthesia from January 1,
      2011, through September 30, 2015, were matched with controls by age, sex, and
      type and year of surgery. MEASUREMENTS: Medical records were reviewed for
      episodes of respiratory depression during phase I recovery and for other
      meaningful perioperative outcomes. MAIN RESULTS: The perioperative courses of 76
      narcoleptic patients and their controls were examined. Compared to controls,
      narcoleptic patients were more often prescribed central nervous system stimulants
      (73.7% vs 4.0%, P<0.001) and antidepressants (46.1% vs 27.6%, P=0.007) and more
      often had obstructive sleep apnea (40.8% vs 19.1%, P<0.001). The intraoperative
      course was similar. The number of episodes of respiratory depression was not
      different between patients and controls (5 [6.6%] vs 12 [7.9%], respectively;
      P=0.80). Narcoleptic patients had a higher frequency of emergency response team
      activations (5 of 76 [6.6%]; 95% CI, 2.2%-14.7%) compared to controls (2 of 152
      [1.3%]; 95% CI, 0.2%-4.7%) (P=0.04). Hemodynamic instability was the indication
      for all emergency response team activations except 1, which was for a narcoleptic
      patient who had excessive postoperative sedation and respiratory depression.
      CONCLUSIONS: Narcoleptic patients had similar intraoperative courses as the
      matched controls, including phase I anesthetic recovery. However, they had a
      higher rate of emergency response team activations than the controls, which
      suggests that patients with narcolepsy may be at increased perioperative risk.

PMID- 28433387
TI  - How do rocker-soled shoes influence the knee adduction moment in people with knee
      osteoarthritis? An analysis of biomechanical mechanisms.
AB  - The primary objective was to examine mechanisms behind previously observed
      changes in the knee adduction moment (KAM) with rocker-soled shoes, in
      participants sub-grouped according to whether they experienced an immediate
      decrease, or increase, in peak KAM. In subgroups where frontal plane knee ground
      reaction force (GRF) lever-arm emerged as a significant predictor, a secondary
      aim was to examine biomechanical factors that contributed to change in this
      parameter. Thirty individuals with symptomatic, radiographic knee osteoarthritis
      (OA) underwent 3D gait analysis in unstable rocker-soled shoes and non-rocker
      soled shoes. Multiple regression analyses, within each subgroup, examined
      relationships between changes in frontal plane knee-GRF lever arm and frontal
      plane resultant GRF magnitude and changes in peak KAM and KAM impulse between
      shoe conditions. In the subgroup that decreased peak KAM with rocker-soled shoes
      (n=23), change in knee-GRF lever arm and frontal plane GRF magnitude at peak KAM
      together were significant predictors of change in peak KAM; however, only change
      in mean knee-GRF lever arm significantly predicted change in KAM impulse.
      Decreased medial GRF magnitude, increased lateral trunk lean towards the stance
      limb and reduced varus/increased valgus hip-knee-ankle angle were associated with
      a lower knee-GRF lever arm in this group, with rocker-soled shoes. In contrast,
      none of the independent variables predicted changes in KAM in the subgroup who
      increased peak KAM with rocker-soled shoes (n=7).

PMID- 28433388
TI  - Magnetic resonance and diffusion tensor imaging analyses indicate heterogeneous
      strains along human medial gastrocnemius fascicles caused by submaximal plantar
      flexion activity.
AB  - Sarcomere length changes are central to force production and excursion of
      skeletal muscle. Previous modeling indicates non-uniformity of that if mechanical
      interaction of muscle with its surrounding muscular and connective tissues is
      taken into account. Hence, quantifying length changes along the fascicles of
      activated human muscle in vivo is crucial, but this is lacking due to technical
      complexities. Combining magnetic resonance imaging deformation analyses and
      diffusion tensor imaging tractography, the aim was to test the hypothesis that
      submaximal plantar flexion activity at 15% MVC causes heterogeneous length
      changes along the fascicles of human medial gastrocnemius (GM) muscle. A general
      fascicle strain distribution pattern shown for all subjects indicates that
      proximal track segments are shortened, whereas distal ones are lengthened (e.g.,
      by 13% and 29%, respectively). Mean fiber direction strains of different tracts
      also shows heterogeneity (for up to 57.5% of the fascicles). Inter-subject
      variability of amplitude and distribution of fascicle strains is notable. These
      findings confirm the hypothesis and are solid indicators for the functionally
      dependent mechanics of human muscle, in vivo. Heterogeneity of fascicle strains
      can be explained by epimuscular myofascial force transmission. To the best of our
      knowledge, this is the first study, which quantified local deformations along
      human skeletal muscle fascicles caused by sustained submaximal activation. The
      present approach and indicated fascicle strain heterogeneity has numerous
      implications for muscle function in health and disease to estimate the muscle's
      contribution to the joint moment and excursion and to evaluate mechanisms of
      muscle injury and several treatment techniques.

PMID- 28433389
TI  - Comparison of methodologies to assess muscle co-contraction during gait.
AB  - The aim of this study was to compare co-contraction index (CCI) computed from
      muscle moments to different co-activation indexes (Co-Act) derived from EMG data
      at the ankle and the knee joint during gait. An EMG-driven model was used to
      estimate muscle moments during over-ground walking gait at a self-selected
      velocity from twelve healthy subjects. The CCI calculated from muscle moments was
      compared with three Co-Acts estimated from the normalized EMG data. The co
      activation methods produced lower values than the CCI during the first double
      support and the swing phase at the ankle joint and during the stance phase at the
      knee joint. The co-activation methods trend is to underestimate the simultaneous
      action of agonist and antagonist contraction. Because the EMG-driven model
      included the muscle mechanical properties (e.g. force-length-velocity
      relationship) and muscle moment-arm, the co-contraction based on major agonist
      and antagonist muscle moment may provide a more confident description of muscle
      action compared to co-activation indexes.

PMID- 28433390
TI  - A computational study of invariant I5 in a nearly incompressible transversely
      isotropic model for white matter.
AB  - The aligned axonal fiber bundles in white matter make it suitable to be modeled
      as a transversely isotropic material. Recent experimental studies have shown that
      a minimal form, nearly incompressible transversely isotropic (MITI) material
      model, is capable of describing mechanical anisotropy of white matter. Here, we
      used a finite element (FE) computational approach to demonstrate the significance
      of the fifth invariant (I5) when modeling the anisotropic behavior of white
      matter in the large-strain regime. We first implemented and validated the MITI
      model in an FE simulation framework for large deformations. Next, we applied the
      model to a plate-hole structural problem to highlight the significance of the
      invariant I5 by comparing with the standard fiber reinforcement (SFR) model. We
      also compared the two models by fitting the experiment data of asymmetric
      indentation, shear test, and uniaxial stretch of white matter. Our results
      demonstrated the significance of I5 in describing shear deformation/anisotropy,
      and illustrated the potential of the MITI model to characterize transversely
      isotropic white matter tissues in the large-strain regime.

PMID- 28433391
TI  - Mechanisms of anterior-posterior stability of the knee joint under load-bearing.
AB  - The anterior-posterior (AP) stability of the knee is an important aspect of
      functional performance. Studies have shown that the stability increases when
      compressive loads are applied, as indicated by reduced laxity, but the mechanism
      has not been fully explained. A test rig was designed which applied combinations
      of AP shear and compressive forces, and measured the AP displacements relative to
      the neutral position. Five knees were evaluated at compressive loads of 0, 250,
      500, and 750N, with the knee at 15 degrees  flexion. At each load, three cycles
      of shear force at +/-100N were applied. For the intact knee under load, the
      posterior tibial displacement was close to zero, due to the upward slope of the
      anterior medial tibial surface. The soft tissues were then resected in sequence
      to determine their role in AP laxity. After anterior cruciate ligament (ACL)
      resection, the anterior tibial displacement increased significantly even under
      load, highlighting its importance in stability. Meniscal resection further
      increased displacement but also the vertical displacement increased, implying the
      meniscus was providing a buffering effect. The PCL had no effect on any of the
      displacements under load. Plowing cartilage deformation and surface friction were
      negligible. This work highlighted the particular importance of the upward slope
      of the anterior medial tibial surface and the ACL to AP knee stability under
      load. The results are relevant to the design of total knees which reproduce
      anatomic knee stability behavior.

PMID- 28433392
TI  - Quantifying rates of cell migration and cell proliferation in co-culture barrier
      assays reveals how skin and melanoma cells interact during melanoma spreading and
      invasion.
AB  - Malignant spreading involves the migration of cancer cells amongst other native
      cell types. For example, in vivo melanoma invasion involves individual melanoma
      cells migrating through native skin, which is composed of several distinct
      subpopulations of cells. Here, we aim to quantify how interactions between
      melanoma and fibroblast cells affect the collective spreading of a heterogeneous
      population of these cells in vitro. We perform a suite of circular barrier assays
      that includes: (i) monoculture assays with fibroblast cells; (ii) monoculture
      assays with SK-MEL-28 melanoma cells; and (iii) a series of co-culture assays
      initiated with three different ratios of SK-MEL-28 melanoma cells and fibroblast
      cells. Using immunostaining, detailed cell density histograms are constructed to
      illustrate how the two subpopulations of cells are spatially arranged within the
      spreading heterogeneous population. Calibrating the solution of a continuum
      partial differential equation to the experimental results from the monoculture
      assays allows us to estimate the cell diffusivity and the cell proliferation rate
      for the melanoma and the fibroblast cells, separately. Using the parameter
      estimates from the monoculture assays, we then make a prediction of the spatial
      spreading in the co-culture assays. Results show that the parameter estimates
      obtained from the monoculture assays lead to a reasonably accurate prediction of
      the spatial arrangement of the two subpopulations in the co-culture assays.
      Overall, the spatial pattern of spreading of the melanoma cells and the
      fibroblast cells is very similar in monoculture and co-culture conditions.
      Therefore, we find no clear evidence of any interactions other than cell-to-cell
      contact and crowding effects.

PMID- 28433393
TI  - Potential mobility of inorganic nutrients and its controls at the sediment-water
      interface in the main path of Kuroshio Current off eastern Taiwan.
AB  - Surface sediments were collected from the main path of Kuroshio Current (KC) off
      eastern Taiwan (ETW), and laboratory incubation was conducted for the study of
      the nutrient exchange at the sediment-water interface. Exchange fluxes of NO3--N,
      NO2--N, NH4+-N, PO43--P and SiO32--Si under simulated site condition were 
      0.0866, 0.00146, 0.0634, -0.00812 and -0.181mmolm-2d-1, respectively. This
      indicated that sediments in the studied area might act as a source of NO2--N and
      NH4+-N and a sink of NO3--N, PO43--P and SiO32--Si. Factors affecting nutrient
      exchange fluxes were studied by changing incubation conditions. Compared with
      some coastal areas in China, the main path of KC off ETW showed relatively low
      nutrient exchange fluxes at the sediment-water interface. It could be inferred
      that the sediment-water exchange of nutrients in the main path of KC off ETW had
      little influence on the downstream nutrient transportation by KC year-round based
      on the results of this research.

PMID- 28433394
TI  - A modelling comparison between received sound levels produced by a marine
      Vibroseis array and those from an airgun array for some typical seismic survey
      scenarios.
AB  - Marine Vibroseis (MV) may provide a marine seismic sound source that has less
      environmental impact than conventional airguns. Modelled sound levels from a
      realistic MV array and airgun array with similar downward energy at frequencies
      <100Hz were compared under three scenarios: shallow, deep, and slope. Changing
      the layout of the MV array's higher frequency sources reduced sound exposure
      levels (SELs) by 4dB. At 100m range this MV was 20dB lower in peak-to-peak sound
      pressure level vs. the airgun array, decreasing to 12dB lower at 5km, the maximum
      modelled range for peak levels. SELs were less clear-cut, but for both shallow
      and deep water, MV produced 8dB lower SELs than the airguns at 100km range
      because of MV's reduced bandwidth. Overall, MV produced lower broadband SELs,
      especially at long range, and lower peak pressure, especially at short range,
      than airguns.

PMID- 28433395
TI  - Distribution, enrichment and source of heavy metals in Rizhao offshore area,
      southeast Shandong Province.
AB  - 50 surface sediments were collected from Rizhao offshore area to determine heavy
      metals (Cu, Pb, Zn, Cr, Cd, As, Hg) pollution. High heavy metal values were
      located near the two ports in the north and south study areas, which was
      consistent with the distribution of fine-grained sediments. According to
      threshold effect level (TEL) and probable effect level (PEL), Cu and As had
      occasionally adverse biological effects on the aquatic ecosystems. The enrichment
      factor (EF) values showed that most of the study area was moderate or moderately
      severe enrichment for As, and minor enrichment for Pb, but Hg was only moderately
      enriched in the river estuaries. The sources of Cu, Zn and Cr were mainly
      influenced by natural weathering processes via the river inputs, whereas Pb, Cd
      and As were mainly derived from anthropogenic sources. Hg may have both natural
      and anthropogenic sources.

PMID- 28433396
TI  - Lambs are Susceptible to Experimental Challenge with Spanish Goat Encephalitis
      Virus.
AB  - Spanish goat encephalitis virus (SGEV) is a member of the genus Flavivirus,
      family Flaviviridae, and causes encephalomyelitis in goats. The aim of this study
      was to determine whether sheep are susceptible to experimental challenge with
      SGEV by two different routes. The results show that SGEV can infect sheep by both
      the subcutaneous and intravenous routes, resulting in neurological clinical
      disease with extensive and severe histological lesions in the central nervous
      system. Lambs challenged subcutaneously developed more severe lesions on the
      ipsilateral side of the brain, but the lesion morphology was similar irrespective
      of the route of challenge. The clinical presentation, pathogenesis, lesion
      morphology and distribution shows that SGEV is very similar to louping ill virus
      (LIV) and therefore any disease control plan must take into account any host
      species and SGEV vectors as potential reservoirs. Furthermore, discriminatory
      diagnostics need to be applied to any sheep or goat suspected of disease due to
      any flavivirus in areas where SGEV and LIV co-exist.

PMID- 28433397
TI  - Multi-drug-resistant Enterobacteriaceae in a Portuguese neonatal intensive care
      unit.

PMID- 28433398
TI  - Multi-state survey of healthcare-associated infections in acute care hospitals in
      Brazil.
AB  - BACKGROUND: Healthcare-associated infections (HCAIs) challenge public health in
      developing countries such as Brazil, which harbour social inequalities and
      variations in the complexity of healthcare and regional development. AIM: To
      describe the prevalence of HCAIs in hospitals in a sample of hospitals in Brazil.
      METHODS: A prevalence survey conducted in 2011-13 enrolled 152 hospitals from the
      five macro-regions in Brazil. Hospitals were classified as large (>=200 beds),
      medium (50-199 beds) or small sized (<50 beds). Settings were randomly selected
      from a governmental database, except for 11 reference university hospitals. All
      patients with >48 h of admission to the study hospitals at the time of the survey
      were included. Trained epidemiologist nurses visited each hospital and collected
      data on HCAIs, subjects' demographics, and invasive procedures. Univariate and
      multivariate techniques were used for data analysis. FINDINGS: The overall HCAI
      prevalence was 10.8%. Most frequent infection sites were pneumonia (3.6%) and
      bloodstream infections (2.8%). Surgical site infections were found in 1.5% of the
      whole sample, but in 9.8% of subjects who underwent surgical procedures. The
      overall prevalence was greater for reference (12.6%) and large hospitals (13.5%),
      whereas medium- and small-sized hospitals presented rates of 7.7% and 5.5%,
      respectively. Only minor differences were noticed among hospitals from different
      macro-regions. Patients in intensive care units, using invasive devices or at
      extremes of age were at greater risk for HCAIs. CONCLUSION: Prevalence rates were
      high in all geographic regions and hospital sizes. HCAIs must be a priority in
      the public health agenda of developing countries.

PMID- 28433399
TI  - Simultaneous 68Ga DOTATATE Positron Emission Tomography/Magnetic Resonance
      Imaging in Meningioma Target Contouring: Feasibility and Impact Upon
      Interobserver Variability Versus Positron Emission Tomography/Computed Tomography
      and Computed Tomography/Magnetic Resonance Imaging.
AB  - AIMS: The increasing use of highly conformal radiation techniques to treat
      meningioma confers a greater need for accurate targeting. Several groups have
      shown that positron emission tomography/computed tomography (PET/CT) information
      alters meningioma targets contoured by single observers, but whether this
      translates into improved accuracy has not been defined. As magnetic resonance
      imaging (MRI) is the cornerstone of meningioma target contouring, simultaneous
      PET/MRI may be superior to PET/CT. We assessed whether 68Ga DOTATATE PET imaging
      (from PET/CT and PET/MRI) reduced interobserver variability (IOV) in meningioma
      target volume contouring. MATERIALS AND METHODS: Ten patients with meningioma
      underwent simultaneous 68Ga DOTATATE PET/MRI followed by PET/CT. They were
      selected as it was anticipated that target volume definition in their cases would
      be particularly challenging. Three radiation oncologists contoured target volumes
      according to an agreed protocol: gross tumour volume (GTV) and clinical target
      volume (CTV) on CT/MRI alone, CT/MRI+PET(CT) and CT/MRI+PET(MRI). GTV/CTV
      Kouwenhoven conformity levels (KCL), regions of contour variation and qualitative
      differences between PET(CT) and PET(MRI) were evaluated. RESULTS: There was
      substantial IOV in contouring. GTV mean KCL: CT/MRI 0.34, CT/MRI+PET(CT) 0.38,
      CT/MRI+PET(MRI) 0.39 (P = 0.06). CTV mean KCL: CT/MRI 0.31, CT/MRI+PET(CT) 0.35,
      CT/MRI+PET(MRI) 0.35 (P = 0.04 for all groups; P > 0.05 for individual pairs).
      One observer consistently contoured largest and one smallest. Observers rarely
      decreased volumes in relation to PET. Most IOV occurred in bone followed by dural
      tail, postoperative bed and venous sinuses. Tumour edges were qualitatively
      clearer on PET(MRI) versus PET(CT), but this did not affect contouring.
      CONCLUSION: IOV in contouring challenging meningioma cases was large and only
      slightly improved with the addition of 68Ga DOTATATE PET. Simultaneous PET/MRI
      for meningioma contouring is feasible, but did not improve IOV versus PET/CT.
      Whether volumes can be safely reduced according to PET requires evaluation.

PMID- 28433400
TI  - An In-home Advanced Robotic System to Manage Elderly Home-care Patients'
      Medications: A Pilot Safety and Usability Study.
AB  - PURPOSE: We examined the safety profile and usability of an integrated advanced
      robotic device and telecare system to promote medication adherence for elderly
      home-care patients. METHODS: There were two phases. Phase I aimed to verify under
      controlled conditions in a single nursing home (n = 17 patients) that no robotic
      malfunctions would hinder the device's safe use. Phase II involved home-care
      patients from 3 sites (n = 27) who were on long-term medication. On-time
      dispensing and missed doses were recorded by the robotic system. Patients' and
      nurses' experiences were assessed with structured interviews. FINDINGS: The 17
      nursing home patients had 457 total days using the device (Phase I; mean, 26.9
      per patient). On-time sachet retrieval occurred with 97.7% of the alerts, and no
      medication doses were missed. At baseline, Phase II home-dwelling patients
      reported difficulty remembering to take their medicines (23%), and 18% missed at
      least 2 doses per week. Most Phase II patients (78%) lived alone. The device
      delivered and patients retrieved medicine sachets for 99% of the alerts. All
      patients and 96% of nurses reported the device was easy to use. IMPLICATIONS:
      This trial demonstrated the safety profile and usability of an in-home advanced
      robotic device and telecare system and its acceptability to patients and nurses.
      It supports individualized patient dosing schedules, patient-provider
      communications, and on-time, in-home medication delivery to promote adherence.
      Real time dose-by-dose monitoring and communication with providers if a dose is
      missed provide oversight generally not seen in home care.

PMID- 28433401
TI  - Relaxed Open Mouth reciprocity favours playful contacts in South American sea
      lions (Otaria flavescens).
AB  - Fine-tuning communication is well documented in mammalian social play which
      relies on a large variety of specific and non-specific signals. Facial
      expressions are one of the most frequent patterns in play communication. The
      reciprocity of facial signals expressed by the players provides information on
      their reciprocal attentional state and on the correct perception/decoding of the
      signal itself. Here, for the first time, we explored the Relaxed Open Mouth
      (ROM), a widespread playful facial expression among mammals, in the South
      American sea lion (Otaria flavescens). In this species, like many others, ROM
      appears to be used as a playful signal as distinct from merely being a biting
      action. ROM was often reciprocated by players. Even though ROM did not vary in
      frequency of emission as a function of the number of players involved, it was
      reciprocated more often during dyadic encounters, in which the players had the
      highest probability to engage in a face-to-face interaction. Finally, we found
      that it was the reciprocation of ROMs, more than their frequency performance,
      that was effective in prolonging playful bouts. In conclusion, ROM is widespread
      in many social mammals and O. flavescens is not an exception. At least in those
      species for which quantitative data are available, ROM seems to be characterized
      by similar design features clearly indicating that the signal underwent to
      similar selective pressures.

PMID- 28433402
TI  - Sensing Bad: Are Co-stimulatory CAR-Expressing gammadelta T Cells Safer?

PMID- 28433403
TI  - [Public health competencies and contents in Spanish university degree programmes
      of Veterinary Medicine].
AB  - OBJECTIVE: To reach a consensus among public health faculty from various Spanish
      universities about the core public health competencies that should be integrated
      into the Veterinary Medicine degree training. METHODS: The 3rd Forum of
      University Professors of Public Health was held at the School of Veterinary
      Medicine of the University of Cordoba (12-13 January 2016). Forty-two university
      professors and lecturers from nine Spanish universities with veterinary degrees
      participated in the forum. They were divided into five working groups during
      three working sessions to identify and classify core public health competencies
      for the Veterinary Medicine degree, propose public health contents for the
      identified competencies and organize such contents in thematic blocks. The
      results were discussed in different plenary sessions. RESULTS: The highest number
      of core competencies was identified in the activities related to the following
      public health functions: "Assessment of the population's health needs" and
      "Developing health policies". The final programme included basic contents
      organized into five units: 1) Fundamentals of public health; 2) Study and
      research in public health; 3) Production, animal health and environment; 4) Food
      security; and 5) Health education. CONCLUSIONS: The public health core
      competencies and contents identified in this Forum may be considered as a
      starting point to update public health training programmes for future veterinary
      professionals.

PMID- 28433404
TI  - [Local food production for school feeding programmes in Spain].
AB  - OBJECTIVE: To identify and characterize initiatives that promote the purchase of
      locally-sourced foods to supply schools and the school centres carrying out the
      initiatives. METHOD: Exploratory, descriptive study based on secondary data and
      key informant reports. A search of governmental and non-governmental initiatives
      was carried out at the autonomous community level. Government initiatives were
      located through school feeding programmes in the different autonomous
      communities, their nutritional guides and representatives of the councils for
      education and agriculture. Non-governmental initiatives were found through their
      own websites and the snowball technique. Initiatives were analysed by their
      geographic distribution, organizational area (government vs. non-government),
      number of school centres carrying out the initiatives, management style and
      organic food purchase. A descriptive analysis of the data was carried out.
      RESULTS: 12 initiatives carried out by 318 schools (2.16% of all the schools with
      food service in Spain) were identified. Among these, 6 are governmental
      initiatives with a scope of 274 schools (1.86%), and 6 are non-governmental
      initiatives with a scope of 44 schools (0.30%). Most of these schools have a
      public management system in place (n=284). All the initiatives provide for the
      purchase of organic food. CONCLUSION: Local food purchase initiatives in Spain
      have a limited reach. However, the existence of a state directive could support
      and strengthen the development of such initiatives, given that school commitment
      is greater when initiatives are driven by the public sector.

PMID- 28433405
TI  - Epidemiology of Toxoplasma gondii among blood donors in Iran: A systematic review
      and meta-analysis.
AB  - INTRODUCTION: Asymptomatic Toxoplasma gondii transmitted from blood donors to
      receiving patients has become a concern. Numerous articles have been published on
      the epidemiology of T. gondii in blood donors in Iran and a systematic review of
      the results shows quite different findings, hence this study was conducted to
      determine the seroprevalence of T. gondii in Iranian blood donors using meta
      analysis. METHODS: We searched for epidemiological studies that were published
      until July 2016 in eight English databases including: Scopus, PubMed, Ovid,
      Science Direct, Cochrane, Web of Science, Springer, Wiley Online Library, and
      four Iranian databases: Magiran, Iranmedex, SID and Medlib as well as Google
      Scholar. To estimate pooled estimator, regarding high heterogeneity and
      significance of I2 index, Random effects model was used. Data analysis was
      conducted using Review Manager Ver5.3.5 and P<0.05 was considered significant.
      RESULTS: Among 10 studies with a sample size of 4538 Iranian blood donors, the
      seroprevalence of T. gondii was calculated to be 34.4% (CI95%: 24.9-43.9). The
      rate in males and females was 33.36% (CI95%: 19.92-46.81) and 37.63% (CI95%:
      20.81-54.45), respectively. The seroprevalence of IgM and IgG antibodies among
      blood donors were 2.74% (CI95%: 0.55-4.92) and 31.84% (CI95%: 20.61-43.08),
      respectively. The seroprevalence of T. gondii was significantly associated
      regarding blood group (P=0.04), but this relation was not significant with blood
      transfusion (P=0.62). CONCLUSION: The results of this review indicate a high
      seroprevalence of T. gondii (about one-third) in Iranian blood donors and
      emphasizes the importance of screening the seroprevalence of T. gondii of donated
      blood in Iranian Blood Transfusion Organization.

PMID- 28433407
TI  - Patient-provider communication in nephrology care for adolescents and young
      adults.
AB  - OBJECTIVE: To compare the relative quantity of talk between providers,
      caregivers, and adolescents and young adults (AYAs) with chronic kidney disease
      (CKD) and how communication differs by age. METHODS: During nephrology clinic
      visits, conversations between AYAs with CKD (N=99, ages 11-20, median=15), their
      caregivers, and providers (N=19) were audiotaped and coded using the Roter
      Interaction Analysis System. Linear mixed models tested AYA age differences in
      talk frequency by AYAs, caregivers, and providers. Post-hoc analyses tested
      differences in talk using AYA age groups. RESULTS: During clinic visits,
      providers spoke the most (63.7%), and caregivers spoke more (22.6%) than AYAs
      (13.7%). Overall talk differed by AYA age in AYAs (p<0.001) and caregivers
      (p<0.05), but not providers. Higher AYA age was associated with more AYA talk
      (biomedical information-giving, partnering, rapport-oriented) and less caregiver
      biomedical information-giving (ps<0.001-0.05). In post-hoc analyses, young adults
      talked more than adolescents; caregiver talk decreased in the middle-adolescent
      group. CONCLUSIONS: Increases in AYA talk occur primarily in young adulthood,
      whereas caregiver talk decreases in middle adolescence. This may indicate an
      appropriate developmental shift but raises concerns about conversational gaps
      during middle-adolescence. PRACTICE IMPLICATIONS: During transition-oriented
      treatment planning, providers should engage both AYAs and caregivers to avoid
      potential gaps in communication.

PMID- 28433406
TI  - Results of the implementation of a multidisciplinary programme of faecal
      microbiota transplantation by colonoscopy for the treatment of recurrent
      Clostridium difficile infection.
AB  - INTRODUCTION: Recurrent Clostridium difficile infection (CDI) is common and often
      difficult to manage. Faecal microbiota transplant (FMT) is an effective
      therapeutic tool in these cases, although its applicability and effectiveness in
      Spain is currently unknown. AIM: To analyse the technical aspects, safety and
      effectiveness of the first consolidated FMT programme in Spain. METHODS:
      Retrospective descriptive study of all patients with recurrent CDI treated with
      FMT performed by colonoscopy in a tertiary centre after the implementation of a
      multidisciplinary protocol between March 2015 and September 2016. RESULTS: A
      total of 13 FMT were performed in 12 patients (11/12; 91.7% women) with a median
      age of 84.6 years (range: 38.2-98.2). Recurrence of CDI was the indication for
      FMT in all cases. Patients had suffered a median of 3 previous episodes of CDI
      (range: 2-6) and all had failed treatment with fidaxomicin. All procedures were
      performed by colonoscopy. Effectiveness with one session of FMT was 91.7% (11/12;
      95% CI: 64.6 to 98.5%). In the non-responder patient, a second FMT was performed
      17 days after the first procedure, with disappearance of symptoms. No side
      effects related to the endoscopic procedure or the FMT were recorded after a
      median follow-up of 6.5 months (range: 1-16 months). Two patients died during
      follow-up due to causes unrelated to FMT. CONCLUSION: FMT by colonoscopy is an
      effective and safe therapeutic alternative in recurrent CDI. It is a simple
      procedure that should be implemented in more centres in Spain.

PMID- 28433408
TI  - Don't need help, don't want help, can't get help: How patients with brain tumors
      account for not using rehabilitation, psychosocial and community services.
AB  - OBJECTIVE: To understand why some adults with primary brain tumors do not use
      support services despite indications of a need for help. METHODS: Nineteen adults
      recently diagnosed with primary brain tumors participated in semi-structured
      interviews. Thematic analysis was used to identify recurrent ways participants
      explained their non-use of support services. RESULTS: Some patients indicated
      that they did not use support services as they did not need help, in particular
      reporting positive experiences relative to their expectations or to others, that
      their needs were met, or difficulties recognizing their needs. Some patients
      reported not wanting help, citing preferences to self-manage, other priorities,
      or negative perceptions of the services available. Many patients identified
      barriers to support service utilization, particularly problems recognizing that
      services could address their needs and that their needs were valid concerns.
      CONCLUSION: The gap between patients' needs and their service use may result from
      patients' expectations from the medical system, shifting of standards for well
      being, cognitive changes, and access issues. PRACTICE IMPLICATIONS: Addressing
      knowledge barriers and perceptions relating to help-seeking, as well as
      recognizing the challenges specific to this patient group in terms of need
      recognition and access issues, may assist in improving patients' physical,
      psychological and social well-being.

PMID- 28433409
TI  - Managing anthelmintic resistance in Parascaris spp.: A modelling exercise.
AB  - A previously described model for the dynamics of the parasitic stages of
      Parascaris spp. was modified to include eggs outside the host and the genetics of
      anthelmintic resistance before being used to address questions regarding the
      development of resistance. Three broad questions were addressed; i) How
      sustainable is the current common practice of treating foals monthly for their
      first year of life (i.e. 12 treatments/year)? ii) Does the timing of treatments
      have an effect on resistance development? (i.e. do certain treatments select for
      resistance more strongly than others?), and iii) How sustainable is the currently
      recommended strategy of targeting ascarid infections in foals with two treatments
      applied during the first five months of life? A range of variations within these
      broad questions were considered, such as the value in rotational deworming,
      whether larvicidal treatments are more selective for resistance, and whether
      combination anthelmintics should be introduced. Twelve anthelmintic treatments at
      monthly intervals resulted in the development of resistance to all the
      anthelmintics used, regardless of how they were used, indicating that such
      intensive treatment frequency is unlikely to be sustainable. The timing of a
      single annual treatment influenced resistance development with treatments at 3
      and 4 months of age being more selective than treatments at other times.
      Treatments administered to foals older than 6 months of age did not select for
      resistance within the timeframe of these simulations. Treatments with activity
      against migrating third stage larvae (ivermectin and a programme of 5 daily
      treatments with fenbendazole) were more selective for resistance than those which
      only killed worms in the intestine. Restricting the number of treatments to young
      foals to two, administered at 2 and 5 months of age slowed the development of
      resistance by allowing a small contribution from susceptible genotype worms to
      subsequent generations. If the interval between treatments was reduced,
      resistance developed more rapidly demonstrating the importance of allowing some
      susceptible worms to reach patency before the second treatment is administered.
      Under a reduced treatment schedule with a clearly defined 'refugium' of
      susceptibility, the use of effective actives in combination appears to offer
      advantages for delaying resistance development. The model offers insights into
      more sustainable drug use strategies and has identified some priority questions
      for future research.

PMID- 28433410
TI  - Echinococcus oligarthrus in the subtropical region of Argentina: First
      integration of morphological and molecular analyses determines two distinct
      populations.
AB  - Echinococcosis is a parasitic zoonosis that is considered as a neglected disease
      by the World Health Organization. The species Echinococcus oligarthrus is one of
      the causative agents of Neotropical echinococcosis, which is a poorly understood
      disease that requires a complex medical examination, may threaten human life, and
      is frequently associated with a low socioeconomic status. Morphological and
      genetic diversity in E. oligarthrus remains unknown. The aim of this work is to
      identify and characterize E. oligarthrus infections in sylvatic animals from the
      Upper Parana Atlantic Forest in the province of Misiones, Argentina, by following
      an integrative approach that links morphological, genetic and ecological aspects.
      This study demonstrates, for the first time, one of the complete life cycles of
      E. oligarthrus in an important ecoregion. The Upper Parana Atlantic Forest
      constitutes the largest remnant continuous forest of the Atlantic Forest,
      representing 7% of the world's biodiversity. This is the first molecular
      determination of E. oligarthrus in Argentina. In addition, the agouti (Dasyprocta
      azarae), the ocelot (Leopardus pardalis) and the puma (Puma concolor) were
      identified as sylvatic hosts of Neotropical echinococcosis caused by E.
      oligarthrus. Mitochondrial and nuclear molecular marker analyses showed a high
      genetic diversity in E. oligarthrus. Moreover, the genetic distance found among
      E. oligarthrus isolates is higher than the one observed among Echinococcus
      granulosus genotypes, which clearly indicates that there are at least two
      different E. oligarthrus populations in Argentina. This study provides valuable
      information to understand the underlying conditions that favour the maintenance
      of E. oligarthrus in sylvatic cycles and to evaluate its zoonotic significance
      for devising preventive measures for human and animal wellbeing.

PMID- 28433411
TI  - Metastatic nasopharyngeal carcinoma: Patterns of care and survival for patients
      receiving chemotherapy with and without local radiotherapy.
AB  - BACKGROUND AND PURPOSE: Radiotherapy (RT) to the primary nasopharyngeal tumor is
      frequently offered to patients with metastatic nasopharyngeal carcinoma (mNPC).
      However, only limited data exist to support RT in this setting. We used the
      National Cancer Database (NCDB) to evaluate outcomes for mNPC patients receiving
      chemotherapy with and without local RT. METHODS: The NCDB was queried for
      patients with mNPC with synchronous metastatic disease at diagnosis who received
      chemotherapy. Overall survival (OS) was analyzed using the Kaplan-Meier method,
      Cox proportional hazards models, and propensity score-matched analyses. RESULTS:
      From 2004 to 2013, 718 cases were identified (39% chemotherapy-alone, 61%
      chemotherapy+RT). At a median follow-up of 4.4years, RT was associated with
      improved survival on univariate analysis (median OS 21.4 vs 15.5months; 5-year OS
      28% vs 10%; p<0.001) and multivariate analyses (HR, 0.61; CI, 0.51-0.74;
      p<0.001). Propensity score analysis with matched baseline characteristics
      demonstrated a similar OS advantage with RT (HR, 0.68; CI, 0.55-0.84; p<0.001).
      The benefits of RT remained consistent in models controlling for single vs multi
      organ metastases and anatomic sites of metastatic involvement. RT dose was an
      independent prognostic factor as both a continuous and categorical variable, with
      OS benefits observed among patients receiving >=50Gy. Long-term survival of
      >10years was only observed in the RT cohort. CONCLUSIONS: This analysis supports
      strategies incorporating local RT with chemotherapy for mNPC. Prospective trials
      evaluating RT integration for mNPC are warranted.

PMID- 28433412
TI  - Quantitative imaging: Correlating image features with the segmentation accuracy
      of PET based tumor contours in the lung.
AB  - The purpose of this study was to investigate the correlation between image
      features extracted from PET images and the accuracy of manually drawn lesion
      contours in the lung. Such correlations are interesting in that they could
      potentially be used in predictive models to help guide physician contouring. In
      this work, 26 synthetic PET datasets were created using an anthropomorphic
      phantom and Monte Carlo simulation. Manual contours of simulated lesions were
      provided by 10 physicians. Contour accuracy was quantified using five commonly
      used similarity metrics which were then correlated with several features
      extracted from the images. Features were sub-divided into three groups using
      intensity, geometry, and texture as categorical descriptors. When averaged among
      the participants, the results showed relatively strong correlations with
      complexity and contrastI (r>=0.65, p<0.001), and moderate correlations with
      several other image features (r>=0.5, p<0.01). The predictive nature of these
      correlations was improved through stepwise regression and the creation of multi
      feature models. Imaging features were also correlated with the standard deviation
      of contouring error in order to investigate inter-observer variability. Several
      features were consistently identified as influential including integral of mean
      curvature and complexity. These relationships further the understanding as to
      what causes variation in the contouring of PET positive lesions.

PMID- 28433413
TI  - Stereotactic ablative radiotherapy in the treatment of low and intermediate risk
      prostate cancer: Is there an optimal dose?
AB  - PURPOSE: To investigate if stereotactic ablative radiotherapy (SABR) dose is
      associated with PSA at 3years (PSA3y) in the treatment of localized prostate
      cancer and to explore predictors of late genitourinary (GU) toxicity. MATERIALS
      AND METHODS: Three prospective trials of SABR were undertaken at our institution:
      1) 35Gy/5 fractions/29days; 2) 40Gy/5 fractions/29days; 3) 40Gy/5 fractions/11 or
      29days. PSA3y was analyzed as a continuous variable. Toxicity was defined as the
      worst new toxicity and assessed using the radiation therapy oncology group (RTOG)
      late morbidity scheme. Univariate and multivariable regression analyses were
      conducted to assess the association between dose and PSA3y, and to explore
      predictors of late grade 2+ GU toxicity. RESULTS: Median PSA3y was 0.64
      (intraquartile range (IQR): 0.41-1.12) and 0.27 (IQR: 0.12-0.55) ng/mL for
      patients treated with 35 and 40Gy respectively. A dose of 40Gy was an independent
      predictor of lower PSA3y on multivariable analysis (p<0.001). Dose of 40Gy (odds
      ratio (OR): 16.69, 95%CI: 5.78, 48.20, p<0.001) and higher International Prostate
      Symptom Score (OR: 1.01, 95%CI: 1.04, 1.16, p=0.001) predicted for late grade 2+
      GU toxicity on multivariable logistic regression. CONCLUSIONS: This analysis
      suggests that higher SABR dose is associated with lower PSA3y. Strategies to
      allow safe SABR dose escalation should be further investigated.

PMID- 28433414
TI  - Diffusion-Tensor Imaging Findings and Cognitive Function Following Hospitalized
      Mixed-Mechanism Mild Traumatic Brain Injury: A Systematic Review and Meta
      Analysis.
AB  - OBJECTIVE: To undertake a systematic review and meta-analysis of the relationship
      between microstructural damage and cognitive function after hospitalized mixed
      mechanism (HMM) mild traumatic brain injury (mTBI). DATA SOURCES: PsycInfo,
      EMBASE, and MEDLINE were used to find relevant empirical articles published
      between January 2002 and January 2016. STUDY SELECTION: Studies that examined the
      specific relationship between diffusion tensor imaging (DTI) and cognitive test
      performance were included. The final sample comprised previously medically and
      psychiatrically healthy adults with HMM mTBI. DATA EXTRACTION: Specific data were
      extracted including mTBI definitional criteria, descriptive statistics, outcome
      measures, and specific results of associations between DTI metrics and cognitive
      test performance. DATA SYNTHESIS: Of the 248 original articles retrieved and
      reviewed, 8 studies met all inclusion criteria and were included in the meta
      analysis. The meta-analysis revealed statistically significant associations
      between reduced white matter integrity and poor performance on measures of
      attention (fractional anisotropy [FA]: d=.413, P<.001; mean diffusivity [MD]: d=
      .407, P=.001), memory (FA: d=.347, P<.001; MD: d=-.568, P<.001), and executive
      function (FA: d=.246, P<.05), which persisted beyond 1 month postinjury.
      CONCLUSIONS: The findings from the meta-analysis provide clear support for an
      association between in vivo markers of underlying neuropathology and cognitive
      function after mTBI. Furthermore, these results demonstrate clearly for the first
      time that in vivo markers of structural neuropathology are associated with
      cognitive dysfunction within the domains of attention, memory, and executive
      function. These findings provide an avenue for future research to examine the
      causal relationship between mTBI-related neuropathology and cognitive
      dysfunction. Furthermore, they have important implications for clinical
      management of patients with mTBI because they provide a more comprehensive
      understanding of factors that are associated with cognitive dysfunction after
      mTBI.

PMID- 28433415
TI  - Effects of Transferring to the Rehabilitation Ward on Long-Term Mortality Rate of
      First-Time Stroke Survivors: A Population-Based Study.
AB  - OBJECTIVE: To assess the long-term health outcomes of acute stroke survivors
      transferred to the rehabilitation ward. DESIGN: Long-term mortality rates of
      first-time stroke survivors during hospitalization were compared among the
      following sets of patients: patients transferred to the rehabilitation ward,
      patients receiving rehabilitation without being transferred to the rehabilitation
      ward, and patients receiving no rehabilitation. SETTING: Retrospective cohort
      study. PARTICIPANTS: Patients (N = 11,419) with stroke from 2005 to 2008 were
      initially assessed for eligibility. After propensity score matching, 390 first
      time stroke survivors were included. INTERVENTIONS: None. MAIN OUTCOME MEASURE:
      Cox proportional hazards regression model was used to assess differences in 5
      year poststroke mortality rates. RESULTS: Based on adjusted hazard ratios (HRs),
      the patients receiving rehabilitation without being transferred to the
      rehabilitation ward (adjusted HR, 2.20; 95% confidence interval [CI], 1.36-3.57)
      and patients receiving no rehabilitation (adjusted HR, 4.00; 95% CI, 2.55-6.27)
      had significantly higher mortality risk than the patients transferred to the
      rehabilitation ward. Mortality rate of the stroke survivors was affected by age
      >=65 years (compared with age <45y; adjusted HR, 3.62), being a man (adjusted HR,
      1.49), having ischemic stroke (adjusted HR, 1.55), stroke severity (Stroke
      Severity Index [SSI] score>=20, compared with SSI score<10; adjusted HR, 2.68),
      and comorbidity (Charlson-Deyo Comorbidity Index [CCI] score>=3, compared with
      CCI score=0; adjusted HR, 4.23). CONCLUSIONS: First-time stroke survivors
      transferred to the rehabilitation ward had a 5-year mortality rate 2.2 times
      lower than those who received rehabilitation without transfer to the
      rehabilitation ward and 4 times lower than those who received no rehabilitation.

PMID- 28433416
TI  - Static Postural Control in Youth With Osteogenesis Imperfecta Type I.
AB  - OBJECTIVES: To assess static postural control in eyes-open and eyes-closed
      conditions in individuals with osteogenesis imperfecta (OI) type I as compared
      with typically developing (TD) individuals and to explore the relation between
      postural control and lower limb muscle function. DESIGN: Cross-sectional study.
      SETTING: Outpatient department of a pediatric orthopedic hospital. PARTICIPANTS:
      A convenience sample (N=38) of individuals with OI type I (n=22; mean age, 13.1y;
      range, 6-21y) and TD individuals (n=16; mean age, 13.1y; range, 6-20y) was
      selected. Participants were eligible if they were between 6 and 21 years and if
      they did not have any fracture or surgery in the lower limb in the 12 months
      before testing. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Postural
      control was assessed through static balance tests and muscle function through
      mechanographic tests on a force platform. Selected postural parameters were path
      length, velocity, 90% confidence ellipse area, and the ellipse's length of the
      mediolateral and anteroposterior axes. Mechanographic parameters were peak force
      and peak power as measured using the multiple two-legged hopping and the single
      two-legged jump test, respectively. RESULTS: Individuals with OI type I had
      poorer postural control than did TD individuals as indicated by longer and faster
      displacements and a larger ellipse area. Muscle function was unrelated to
      postural control in the OI group. Removing visual information resulted in a
      larger increase in postural control parameters in the OI group than in the TD
      group. CONCLUSIONS: A proprioceptive deficit could explain poorer postural
      control in individuals with OI type I.

PMID- 28433417
TI  - Mechanistic insights into epigenetic modulation of ethanol consumption.
AB  - There is growing evidence that small-molecule inhibitors of epigenetic
      modulators, such as histone deacetylases (HDAC) and DNA methyltransferases
      (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular
      and cellular processes underlying this behavioral effect are poorly understood.
      We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs,
      decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol
      consumption using two tests: binge-like drinking in the dark (DID) and chronic
      intermittent every other day (EOD) drinking. Decitabine but not SAHA reduced
      ethanol consumption in both tests. We further investigated decitabine's effects
      on the brain's reward pathway by gene expression profiling in the ventral
      tegmental area (VTA), using RNA sequencing and electrophysiological recordings
      from VTA dopaminergic neurons. Decitabine-induced decreases in EOD drinking were
      associated with global changes in gene expression, implicating regulation of
      cerebral blood flow, extracellular matrix organization, and neuroimmune functions
      in decitabine actions. In addition, an in vivo administration of decitabine
      shortened ethanol-induced excitation of VTA dopaminergic neurons in vitro,
      suggesting that decitabine reduces ethanol drinking via changes in the reward
      pathway. Taken together, our data suggest a contribution of both neuronal and non
      neuronal mechanisms in the VTA in the regulation of ethanol consumption.
      Decitabine and other epigenetic compounds have been approved for cancer
      treatment, and understanding their mechanisms of actions in the brain may assist
      in repurposing these drugs and developing novel therapies for central disorders,
      including drug addiction.

PMID- 28433418
TI  - Binge alcohol alters PNPLA3 levels in liver through epigenetic mechanism
      involving histone H3 acetylation.
AB  - The human PNPLA3 (patatin-like phospholipase domain-containing 3) gene codes for
      a protein which is highly expressed in adipose tissue and liver, and is
      implicated in lipid homeostasis. While PNPLA3 protein contains regions homologous
      to functional lipolytic proteins, the regulation of its tissue expression is
      reflective of lipogenic genes. A naturally occurring genetic variant of PNPLA3 in
      humans has been linked to increased susceptibility to alcoholic liver disease. We
      have examined the modulatory effect of alcohol on PNPLA3 protein and mRNA
      expression as well as the association of its gene promoter with acetylated
      histone H3K9 by chromatin immunoprecipitation (ChIP) assay in rat hepatocytes in
      vitro, and in vivo in mouse and rat models of acute binge, chronic, and chronic
      followed by acute binge ethanol administration. Protein expression of PNPLA3 was
      significantly increased by alcohol in all three models used. PNPLA3 mRNA also
      increased, albeit to a varying degree. ChIP assay using H3AcK9 antibody showed
      increased association with the promoter of PNPLA3 in hepatocytes and in mouse
      liver. This was less evident in rat livers in vivo except under chronic
      treatment. It is concluded for the first time that histone acetylation plays a
      role in the modulation of PNPLA3 levels in the liver exposed to binge ethanol
      both in vitro and in vivo.

PMID- 28433419
TI  - Disconnect between alcohol-induced alterations in chromatin structure and gene
      transcription in a mouse embryonic stem cell model of exposure.
AB  - Alterations to chromatin structure induced by environmental insults have become
      an attractive explanation for the persistence of exposure effects into subsequent
      life stages. However, a growing body of work examining the epigenetic impact that
      alcohol and other drugs of abuse exert consistently notes a disconnection between
      induced changes in chromatin structure and patterns of gene transcription. Thus,
      an important question is whether perturbations in the 'histone code' induced by
      prenatal exposures to alcohol implicitly subvert gene expression, or whether the
      hierarchy of cellular signaling networks driving development is such that they
      retain control over the transcriptional program. To address this question, we
      examined the impact of ethanol exposure in mouse embryonic stem cells cultured
      under 2i conditions, where the transcriptional program is rigidly enforced
      through the use of small molecule inhibitors. We find that ethanol-induced
      changes in post-translational histone modifications are dose-dependent, unique to
      the chromatin modification under investigation, and that the extent and direction
      of the change differ between the period of exposure and the recovery phase.
      Similar to in vivo models, we find post-translational modifications affecting
      histone 3 lysine 9 are the most profoundly impacted, with the signature of
      exposure persisting long after alcohol has been removed. These changes in
      chromatin structure associate with dose-dependent alterations in the levels of
      transcripts encoding Dnmt1, Uhrf1, Tet1, Tet2, Tet3, and Polycomb complex members
      Eed and Ezh2. However, in this model, ethanol-induced changes to the chromatin
      template do not consistently associate with changes in gene transcription, impede
      the process of differentiation, or affect the acquisition of monoallelic patterns
      of expression for the imprinted gene Igf2R. These findings question the inferred
      universal relevance of epigenetic changes induced by drugs of abuse and suggest
      that changes in chromatin structure cannot unequivocally explain dysgenesis in
      isolation.

PMID- 28433420
TI  - DNA Methylation program in normal and alcohol-induced thinning cortex.
AB  - While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders
      (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits
      are not clear. DNA methylation is known to regulate early development and tissue
      specification through gene regulation. Here, we examined DNA methylation in the
      onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6 (B6)
      mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7
      16, and their embryos were harvested at E17, along with isocaloric liquid diet
      and lab chow controls. Cortical neuroanatomy, neural phenotypes, and epigenetic
      markers of methylation were assessed using immunohistochemistry, Western blot,
      and methyl-DNA assays. We report that cortical thickness, neuroepithelial
      proliferation, and neuronal migration and maturity were found to be deterred by
      alcohol at E17. Simultaneously, DNA methylation, including 5-methylcytosine (5mC)
      and 5-hydroxcylmethylcytosine (5hmC), which progresses as an intrinsic program
      guiding normal embryonic cortical development, was severely affected by in utero
      alcohol exposure. The intricate relationship between cortical thinning and this
      DNA methylation program disruption is detailed and illustrated. DNA methylation,
      dynamic across the multiple cortical layers during the late embryonic stage, is
      highly disrupted by fetal alcohol exposure; this disruption occurs in tandem with
      characteristic developmental abnormalities, ranging from structural to molecular.
      Finally, our findings point to a significant question for future exploration:
      whether epigenetics guides neurodevelopment or whether developmental conditions
      dictate epigenetic dynamics in the context of alcohol-induced cortical
      teratogenesis.

PMID- 28433421
TI  - Strain-specific programming of prenatal ethanol exposure across generations.
AB  - Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted
      from in utero-exposed F1 generation to their F2 offspring. This type of
      transmission is modulated by genetic and epigenetic mechanisms. This study
      investigated the intergenerational consequences of prenatal exposure to a low
      ethanol dose (1 g/kg) during gestational days 17-20, on ethanol-induced hypnosis
      in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long
      Evans and Sprague-Dawley male rats were tested for sensitivity to ethanol-induced
      hypnosis at a 3.5-g/kg or 4.5-g/kg ethanol dose using the loss of righting reflex
      (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol
      induced hypnosis in the ethanol-exposed animals in these two strains and in both
      generations. Interestingly, we only found this effect in Sprague-Dawley rats.
      Lastly, we investigated PAE related changes in expression of GABAA receptor
      alpha1, alpha4, and delta subunits in the cerebral cortex of the PAE sensitive
      Sprague-Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA
      receptor subunits' expression in the F1 and F2 PAE groups compared to control
      animals. GABAA receptor alpha1, alpha4, and delta subunits protein expressions
      were quantified in the cerebral cortex of F1 and F2 male adolescents by western
      blotting. PAE did not alter cerebral cortical GABAA receptor subunit expressions
      in the F1 generation, but it decreased GABAA receptor alpha4 and delta subunits'
      expressions in the F2 generation, and had a tendency to decrease alpha1 subunit
      expression. We also found correlations between some of the subunits in both
      generations. These strain-dependent vulnerabilities to ethanol sensitivity, and
      intergenerational PAE-mediated changes in sensitivity to alcohol indicate that
      genetic and epigenetic factors interact to determine the outcomes of PAE animals
      and their offspring.

PMID- 28433422
TI  - Postnatal choline supplementation selectively attenuates hippocampal microRNA
      alterations associated with developmental alcohol exposure.
AB  - Prenatal alcohol exposure can result in a range of physical, neuropathological,
      and behavioral alterations, collectively termed fetal alcohol spectrum disorders
      (FASD). We have shown that supplementation with the nutrient choline reduces the
      severity of developmental alcohol-associated deficits in hippocampal-dependent
      behaviors and normalizes some aspects of hippocampal cholinergic development and
      DNA methylation patterns. Alcohol's developmental effects may also be mediated,
      in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene
      translation. To determine whether choline supplementation alters ethanol's long
      lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day
      ethanol from postnatal days (PD) 4-9 via intubation; controls received sham
      intubations. Subjects were treated with choline chloride (100 mg/kg/day) or
      saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were
      sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was
      assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol
      significantly increased miRNA expression variance, an effect that was attenuated
      with choline supplementation. Cluster analysis of stably expressed miRNAs that
      exceeded an ANOVA p < 0.05 criterion indicated that for both male and female
      offspring, control and ethanol-exposed groups were most dissimilar from each
      other, with choline-supplemented groups in between. MiRNAs that expressed an
      average 2-fold change due to ethanol exposure were further analyzed to identify
      which ethanol-sensitive miRNAs were protected by choline supplementation. We
      found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR
      200c was induced by ethanol exposure and that choline prevented this effect.
      Collectively, our data show that choline supplementation can normalize
      disturbances in miRNA expression following developmental alcohol exposure and can
      protect specific miRNAs from induction by ethanol. These findings have important
      implications for the mechanisms by which choline may serve as a potential
      treatment for FASD.

PMID- 28433424
TI  - Letter to the Editor on "Day of Surgery and Surgical Start Time Affect Hospital
      Length of Stay After Total Hip Arthroplasty".

PMID- 28433425
TI  - Effect of Spinal Fusion Surgery on Total Hip Arthroplasty Outcomes: A Matched
      Comparison Study.
AB  - BACKGROUND: Studies regarding postoperative outcomes after primary total hip
      arthroplasty (THA) in patients who have comorbid factors tend to focus on medical
      diseases. However, there is a paucity of literature examining the effect of a
      patient's orthopedic surgical history on outcomes after THA. Significantly, there
      are currently no studies on the effect of spinal fusion surgery on THA outcomes.
      METHODS: A review of 82 consecutive patients who had prior spinal fusion surgery
      who underwent elective THA from January 1, 2006 to December 31, 2015, was
      conducted. A matching cohort of 82 patients was selected from the remaining THA
      patients to maintain a 1:1 ratio control group. This cohort of 82 patients was
      matched for age, gender, body mass index +/-5, preoperative Oxford score +/-10,
      total Short Form-36 score +/-10, and total Western Ontario and McMaster
      Universities Arthritis Index (WOMAC) score +/-50. Data on the same functional
      outcomes were prospectively collected at 6-month and 2-year follow-up for
      comparison. RESULTS: Patients without spinal fusion had better outcome scores
      than patients with prior spinal fusion, specifically in their 6-month WOMAC
      scores (253.33-225.07; P = .046), their 2-year Short Form-36 total scores (79.71
      69.21; P = .041), and their 2-year WOMAC scores (213.5-267.41; P = .054).
      CONCLUSION: This study demonstrates that patients with prior spinal fusion had
      worse outcomes after THA than patients without prior spinal fusion. This has
      clinical significance in counseling patients with previous spinal fusion
      undergoing THA.

PMID- 28433423
TI  - Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice
      changes across ethanol dependence, withdrawal, and abstinence.
AB  - Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive
      ethanol consumption. Recent studies support the involvement of epigenetic
      mechanisms in the development of AUD. Studies carried out so far have focused on
      a few specific epigenetic modifications. The goal of this project was to
      investigate gene expression changes of epigenetic regulators that mediate a broad
      array of chromatin modifications after chronic alcohol exposure, chronic alcohol
      exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21
      days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone
      (WSP) selected mouse lines. We found that chronic vapor exposure to highly
      intoxicating levels of ethanol alters the expression of several chromatin
      remodeling genes measured by quantitative PCR array analyses. The identified
      effects were independent of selected lines, which, however, displayed baseline
      differences in epigenetic gene expression. We reported dysregulation in the
      expression of genes involved in histone acetylation, deacetylation, lysine and
      arginine methylation and ubiquitinationhylation during chronic ethanol exposure
      and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are
      consistent with decreased histone acetylation and with decreased deposition of
      the permissive ubiquitination mark H2BK120ub, associated with reduced
      transcription. On the other hand, ethanol-induced changes in the expression of
      genes involved in histone lysine methylation are consistent with increased
      transcription. The net result of these modifications on gene expression is likely
      to depend on the combination of the specific histone tail modifications present
      at a given time on a given promoter. Since alcohol does not modulate gene
      expression unidirectionally, it is not surprising that alcohol does not
      unidirectionally alter chromatin structure toward a closed or open state, as
      suggested by the results of this study.

PMID- 28433426
TI  - Initial Stability of Cemented vs Cementless Tibial Components Under Cyclic Load.
AB  - BACKGROUND: Cement fixation of total knee components remains the gold standard
      despite resurgence in cementless fixation with the goal of long-term durable
      fixation. Initial stability is paramount to achieve bony ingrowth of cementless
      components. METHODS: Twelve cemented and cementless tibial baseplates were
      implanted into sawbones and tested using a physiological medial-lateral load
      distribution for 10,000 cycles to represent 8 weeks of in vivo function.
      Micromotion was measured at 5 locations around the baseplate during loading.
      RESULTS: Cycling had a significant effect on the change in micromotion between
      maximum and minimum loads at the anterior, medial, lateral, posteromedial, and
      posterolateral tray edge locations. A significant effect of fixation technique
      was detected for the anterior (P < .001), medial (P = .002), and lateral (P =
      .0056) locations but not for the posteromedial (P = .36) or posterolateral (P =
      .82) locations. Differences in micromotion between cemented and cementless
      components did not exceed 150 MUm at any tested location. CONCLUSION: The
      micromotion experienced by cementless tibial components in the present study may
      indicate a lower initial mechanical stability than the cemented group. However,
      this difference in initial stability may be subclinical because the differences
      between average cemented and cementless micromotion were <150 MUm at all measured
      locations under the loading regime implemented.

PMID- 28433427
TI  - Do Medial Pivot Kinematics Correlate With Patient-Reported Outcomes After Total
      Knee Arthroplasty?
AB  - BACKGROUND: Many total knee arthroplasty (TKA) implants are designed to
      facilitate a medial pivot kinematic pattern. The purpose of this study was to
      determine whether intraoperative medial pivot kinematic patterns are associated
      with improved patient outcomes. METHODS: A retrospective review of consecutive
      primary TKAs was performed. Sensor-embedded tibial trials determined kinematic
      patterns intraoperatively. The center of rotation (COR) was identified from 0
      degrees  to 90 degrees  and from 0 degrees  to terminal flexion, and designated
      medial-pivot or non-medial pivot based on accepted criteria. Patient-reported
      outcomes were measured preoperatively and at minimum one-year follow-up. RESULTS:
      The analysis cohort consisted of 141 TKAs. Mean age and median BMI were 63.7
      years and 33.8 kg/m2, respectively. Forty-percent of TKAs demonstrated a medial
      pivot kinematic pattern intraoperatively. A medial pivot pattern was more common
      with posterior cruciate-retaining (CR) and posterior cruciate
      substituting/anterior lipped (CS) implants when compared to posterior stabilized
      (PS) TKAs (P <=.0150). Regardless of bearing type, minimum one-year Knee Society
      scores and UCLA activity level did not significantly differ based on medial vs
      non-medial pivot patterns (P >=.292). For patients with posterior cruciate
      sacrificing implants, there were trends for greater median improvement in Knee
      Society objective (46 vs 31.5 points, P =.057) and satisfaction (23 vs 14 points,
      P =.067) scores in medial pivot knees. CONCLUSION: A medial pivot pattern may not
      significantly govern clinical success after TKA based on intraoperative
      kinematics and modern outcome measures. Further research is warranted to
      determine if a particular kinematic pattern promotes optimal clinical outcomes.

PMID- 28433428
TI  - Effect of Risk Acceptance for Bundled Care Payments on Clinical Outcomes in a
      High-Volume Total Joint Arthroplasty Practice After Implementation of a
      Standardized Clinical Pathway.
AB  - BACKGROUND: The Bundled Payments for Care Improvement (BPCI) initiative and the
      Arkansas Payment Improvement (API) initiative seek to incentivize reduced costs
      and improved outcomes compared with the previous fee-for-service model. Before
      participation, our practice initiated a standardized clinical pathway (CP) to
      reduce length of stay (LOS), readmissions, and discharge to postacute care
      facilities. METHODS: This practice implemented a standardized CP focused on
      patient education, managing patient expectations, and maximizing cost outcomes.
      We retrospectively reviewed all primary total joint arthroplasty patients during
      the initial 2-year "at risk" period for both BPCI and API and determined
      discharge disposition, LOS, and readmission rate. RESULTS: During the "at risk"
      period, the average LOS decreased in our total joint arthroplasty patients and
      our patients discharged home >94%. Patients within the BPCI group had a decreased
      discharge to home and decreased readmission rates after total hip arthroplasty,
      but also tended to be older than both API and nonbundled payment patients.
      CONCLUSION: While participating in the BPCI and API, continued use of a
      standardized CP in a high-performing, high-volume total joint practice resulted
      in maintenance of a low-average LOS. In addition, BPCI patients had similar
      outcomes after total knee arthroplasty, but had decreased rates of discharge to
      home and readmission after total hip arthroplasty.

PMID- 28433429
TI  - Immunological function of Langerhans cells in HIV infection.
AB  - BACKGROUND: Langerhans cells (LCs) are one of the initial target cells for HIV
      following sexual exposure and they are productively infected by HIV. HIV-infected
      LCs migrate to the draining lymph nodes (dLNs) and transmit the virus to CD4+ T
      cells, leading to the dissemination of HIV. In contrast with the role of LCs in
      initial HIV acquisition, little is known about the modulation of immune responses
      by HIV-infected LCs. OBJECTIVE: We aimed to elucidate the induction of HIV
      specific CD8+ T cells and regulatory T cells (Tregs), both of which play
      important roles in regulating the progression of HIV infection. METHODS: We
      examined the inducibility of HLA-A*0201 restricted HIV-specific CD8+ T cells and
      Tregs by HIV-primed LCs or HIV-primed dendritic cells (DCs) as a control.
      RESULTS: The number of HIV-specific CD8+ T cells induced by HIV-primed monocyte
      derived LCs (mLCs) was significantly higher than that by HIV-primed monocyte
      derived DCs (mDCs). Additionally, HIV-specific CD8+ T cells induced by HIV-primed
      mLCs produced more IFN-gamma than HIV-nonspecific CD8+ T cells. HIV-primed human
      epidermal LCs also induced IFN-gamma-producing HIV-specific CD8+ T cells. As for
      the induction of Tregs, HIV-primed mLCs and human epidermal LCs significantly
      impaired the induction of FoxP3hiCD45RA- effector Tregs than HIV-unprimed mLCs
      and human epidermal LCs. CONCLUSIONS: HIV-primed LCs trigger beneficial immune
      responses against HIV infection through the increased induction of HIV-specific
      CD8+ T cells and the decreased induction of effector Tregs in the initial phase
      of HIV infection, thereby contributing to the prolonged onset of AIDS.

PMID- 28433430
TI  - Complementary effect of hydroquinone and retinoic acid on corneocyte desquamation
      with their combination use.
AB  - BACKGROUND: Retinoic acid (RA) enhances skin-lightening capabilities of
      hydroquinone (HQ), at least in part, by facilitating desquamation which leads to
      increase penetration of HQ. The desquamation also affects skin irritation levels.
      The mechanism of RA-induced desquamation, however, has not been completely
      explored and no such data has been available for HQ uses. OBJECTIVE: To examine
      the role of HQ, RA, and their combination in the desquamation. METHODS: Primary
      cultured normal human keratinocytes, which were treated with HQ and/or RA in
      presence or absence of serine-specific inhibitor Kazal type5 (SPINK5)/lympho
      epithelial Kazal-type-related inhibitor (LEKTI) knockdown or recombinant human
      SPINK5/LEKTI, and biopsied skin samples applied with HQ or RA were examined.
      Expression levels of corneodesmosin (CDSN), desmocollin1 (DSC1), kallikrein5
      (KLK5), KLK7, and SPINK5/LEKTI, and proteolysis activity against extracted human
      skin epidermal protein were determined using time-course real-time PCR, Western
      blotting, ELISA, and immunofluorescence staining. RESULTS: HQ increased but RA
      decreased the synthesis of CDSN and DSC1. HQ reduced corneodesmosome degradation
      by the upregulation of SPINK5/LEKTI, whereas RA showed opposite results without
      upregulation of SPINK5/LEKTI. The combination of HQ and RA was close to the sum
      of the individual components. CONCLUSIONS: HQ reduced corneocyte desquamation.
      However, RA enhanced desquamation. The combination induced more desquamation than
      HQ but less than RA.

PMID- 28433431
TI  - Application of structured support vector machine backpropagation to a
      convolutional neural network for human pose estimation.
AB  - In this study, for the first time, we show how to formulate a structured support
      vector machine (SSVM) as two layers in a convolutional neural network, where the
      top layer is a loss augmented inference layer and the bottom layer is the normal
      convolutional layer. We show that a deformable part model can be learned with the
      proposed structured SVM neural network by backpropagating the error of the
      deformable part model to the convolutional neural network. The forward
      propagation calculates the loss augmented inference and the backpropagation
      calculates the gradient from the loss augmented inference layer to the
      convolutional layer. Thus, we obtain a new type of convolutional neural network
      called an Structured SVM convolutional neural network, which we applied to the
      human pose estimation problem. This new neural network can be used as the final
      layers in deep learning. Our method jointly learns the structural model
      parameters and the appearance model parameters. We implemented our method as a
      new layer in the existing Caffe library.

PMID- 28433432
TI  - ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial
      Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam
      Boost for High- and Intermediate-Risk Prostate Cancer.
AB  - PURPOSE: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and
      erectile dysfunction in a randomized trial comparing 2 methods of dose escalation
      for high- and intermediate-risk prostate cancer. METHODS AND MATERIALS: ASCENDE
      RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated
      Radiation Therapy) enrolled 398 men, median age 68 years, who were then
      randomized to either a standard arm that included 12 months of androgen
      deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated
      external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm
      that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic
      visits, investigators recorded GU and GI morbidity and information on urinary
      continence, catheter use, and erectile function. Exclusion of 15 who received
      nonprotocol treatment and correction of 14 crossover events left 195 men who
      actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was
      6.5 years. RESULTS: The LDR-PB boost increased the risk of needing temporary
      catheterization and/or requiring incontinence pads. At 5 years the cumulative
      incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT
      (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade
      3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The
      5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2%
      for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than
      the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men
      reporting adequate baseline erections, 45% of LDR-PB patients reported similar
      erectile function at 5 years, versus 37% after DE-EBRT (P=.30). CONCLUSIONS: The
      incidence of acute and late GU morbidity was higher after LDR-PB boost, and there
      was a nonsignificant trend for worse GI morbidity. No differences in the
      frequency of erectile dysfunction were observed.

PMID- 28433433
TI  - Design, selection, and development of cyclic peptide ligands for human
      erythropoietin.
AB  - This work presents the selection and characterization of erythropoietin (EPO)
      binding cyclic peptide ligands. The sequences were selected by screening a
      focused library of cyclic depsipeptides cyclo[(Nalpha-Ac)Dap(A)-X1-X6-AE], whose
      structure and amino acid compositions were tailored to mimic the EPO receptor.
      The sequences identified through library screening were synthesized on
      chromatographic resin and characterized via binding-and-elution studies against
      EPO to select a pool of candidate ligands. Sequences with higher hydrophobicity
      consistently showed stronger binding to EPO, with the exception of FSLLSH, which
      was noted for its lower hydrophobicity and high EPO binding. Mutagenesis studies
      performed on FSLLSH with natural and non-natural amino acid substitutions led to
      the identification of critical EPO-binding determinants, and the discovery of new
      peptide ligands. In particular, histidine-scanning mutagenesis performed on three
      lead sequences yielded the discovery of variants whose EPO-binding is more pH
      sensitive, which facilitates EPO recovery. Selected ligands were studied to
      correlate the elution yield to the salinity of the binding buffer and the elution
      pH. Elution yields were consistently higher when EPO binding was performed at low
      ionic strength. The crystal structures of lead cyclic peptides were docked in
      silico against EPO to estimate the binding affinity in solution. Isotherm
      adsorption studies performed on FSLLSH indicated that the cyclic version of the
      ligand (KD=0.46MUM) has a higher affinity for EPO than its corresponding linear
      variant (KD=1.44MUM). Collectively, these studies set the stage for use of the
      cyclic peptide ligands as EPO purification and detection tools.

PMID- 28433434
TI  - Non-conventional solvents in liquid phase microextraction and aqueous biphasic
      systems.
AB  - The development of rapid, convenient, and high throughput sample preparation
      approaches such as liquid phase microextraction techniques have been continuously
      developed over the last decade. More recently, significant attention has been
      given to the replacement of conventional organic solvents used in liquid phase
      microextraction techniques in order to reduce toxic waste and to improve
      selectivity and/or extraction efficiency. With these objectives, non-conventional
      solvents have been explored in liquid phase microextraction and aqueous biphasic
      systems. The utilized non-conventional solvents include ionic liquids, magnetic
      ionic liquids, and deep eutectic solvents. They have been widely used as
      extraction solvents or additives in various liquid phase microextraction modes
      including dispersive liquid-liquid microextraction, single-drop microextraction,
      hollow fiber-liquid phase microextraction, as well as in aqueous biphasic
      systems. This review provides an overview into the use of non-conventional
      solvents in these microextraction techniques in the past 5 years (2012-2016).
      Analytical applications of the techniques are also discussed.

PMID- 28433435
TI  - Fabric phase sorptive extraction as a reliable tool for rapid screening and
      detection of freshness markers in oranges.
AB  - A simple, fast and sensitive analyte extraction method based on fabric phase
      sorptive extraction (FPSE) followed by gas chromatography-mass spectrometry (GC
      MS) and ultra-performance liquid chromatography-quadrupole time of flight mass
      spectrometry (UPLC-QTOF-MS) analysis was developed for the analysis of 12
      volatile compounds that represent most of the principal chemical families
      possessing different polarities and volatilities. Five FPSE media coated with
      different sol-gel sorbent chemistries having different polarities and
      selectivities were studied: long chain poly(dimethylsiloxane) (PDMS), short chain
      poly(tetrahydrofuran) (PTHF), Carbowax 20M (CW20M), short chain poly(dimethyl
      siloxane) (SC PDMS) and polyethylene glycol-polypropylene glycol-polyethylene
      glycol triblock copolymer (PEG-PPG-PEG). CW20M coated FPSE media was found to be
      the most efficient extraction media for the analytes of interest in the intended
      study. The developed methodology was applied to the analysis of orange juice
      obtained from fresh oranges and oranges after storing at 5 degrees C for two
      months in order to identify the best chemical markers, both volatiles and non
      volatiles, attributed to the freshness of orange. For this purpose, aliquots of
      the same juice extracts were analysed by GC-MS as well as by UPLC-QTOF-MS.
      Monoterpenes and terpenoids, such as terpinene, citronellal or estragole were
      among the volatile compounds that endured the biggest decrease after the extended
      storage period. Three non-volatile compounds including one amide (subaphyllin)
      and two flavanoids (tangeretin and nobiletin) also showed a clear decrease in
      signal intensity (>70%) after orange stored for two months.

PMID- 28433437
TI  - Optimal Ultrasound Exposure Conditions for Maximizing C2C12 Muscle Cell
      Proliferation and Differentiation.
AB  - Described here is an in vitro systematic investigation of the effects on C2C12
      myoblasts of exposure to finely controlled and repeatable low-intensity pulsed
      ultrasound of different frequencies (500 kHz, 1 MHz, 3 MHz and 5 MHz) and
      different intensities (250, 500 and 1000 mW/cm2). An in-house stimulation system
      and an ultrasound-transparent cell culture well minimized reflections and
      attenuations, allowing precise control of ultrasound delivery. Results indicated
      that a 3 MHz stimulation at 1 W/cm2 intensity maximized cell proliferation in
      comparison with the other exposure conditions and untreated controls. In
      contrast, cell differentiation and the consequent formation of multinucleated
      myotubes were maximized by 1 MHz stimulation at 500 mW/cm2 intensity. The highly
      controlled exposure conditions employed allowed precise correlation of the
      ultrasound delivery to the bio-effects produced, thus overcoming the
      inconsistency of some results available in the literature and contributing to the
      potential of ultrasound treatment for muscle therapy and regeneration.

PMID- 28433436
TI  - Subharmonic-Aided Pressure Estimation for Monitoring Interstitial Fluid Pressure
      in Tumors: Calibration and Treatment with Paclitaxel in Breast Cancer Xenografts.
AB  - Interstitial fluid pressure (IFP) in rats with breast cancer xenografts was non
      invasively estimated using subharmonic-aided pressure estimation (SHAPE) versus
      an invasive pressure monitor. Moreover, monitoring of IFP changes after
      chemotherapy was assessed. Eighty-nine rats (calibration n = 25, treatment n =
      64) were injected with 5 * 106 breast cancer cells (MDA-MB-231). Radiofrequency
      signals were acquired (39 rats successfully imaged) with a Sonix RP scanner (BK
      Ultrasound, Richmond, BC, Canada) using a linear array (L9-4, transmit/receive:
      8/4 MHz) after administration of Definity (Lantheus Medical Imaging, North
      Billerica, MA, USA; 180 MUL/kg) and compared with readings from an invasive
      pressure monitor (Stryker, Berkshire, UK). An inverse linear relationship was
      established between tumor IFP and SHAPE (y = -1.06x + 28.27, r = -0.69, p = 0.01)
      in the calibration group. Use of this relationship in the treatment group
      resulted in r = 0.74 (p < 0.05) between measured (pressure monitor) and SHAPE
      estimated IFP (average error: 6.24 mmHg). No significant before/after differences
      were observed with respect to paclitaxel treatment (5 mg/kg, Mayne Pharma,
      Paramus, NJ, USA) with either method (p >= 0.15).

PMID- 28433438
TI  - Analgesic Effects of Transcutaneous Ultrasound Nerve Stimulation in a Rat Model
      of Oxaliplatin-Induced Mechanical Hyperalgesia and Cold Allodynia.
AB  - This study investigated the effects and underlying mechanisms of therapeutic
      ultrasound (TUS) in a rat model of oxaliplatin-induced peripheral neuropathy.
      Animals received a total of eight injections with oxaliplatin (4 mg/kg),
      administered at 3-d intervals. TUS intervention (1 MHz, 0.5 W/cm2) started on the
      fifth oxaliplatin administration and continued for 10 consecutive d. Sensory
      behavioral examinations, protein levels of transient receptor potential channels
      (TRPM8 and TRPV1) in dorsal root ganglia (DRG) and substance P (SP) in spinal
      dorsal horn were examined. Results indicated that TUS can reduce mechanical and
      cold hyper-responsive behaviors caused by repeated administration of oxaliplatin.
      Oxaliplatin-related increases in protein levels of TRPM8 in DRG and SP in the
      dorsal horn were also reduced after TUS. Taken together, the results revealed
      beneficial effects of TUS on oxaliplatin-induced mechanical hyperalgesia and cold
      allodynia and suggested involvement of TUS biochemicals in suppressing TRPM8 in
      DRG and SP in spinal cords.

PMID- 28433439
TI  - Cardiac Amyloidosis Shows Decreased Diastolic Function as Assessed by
      Echocardiographic Parameterized Diastolic Filling.
AB  - Cardiac amyloidosis is a rare but serious condition with poor survival. One of
      the early findings by echocardiography is impaired diastolic function, even
      before the development of cardiac symptoms. Early diagnosis is important,
      permitting initiation of treatment aimed at improving survival. The parameterized
      diastolic filling (PDF) formalism entails describing the left ventricular filling
      pattern during early diastole using the mathematical equation for the motion of a
      damped harmonic oscillator. We hypothesized that echocardiographic PDF analysis
      could detect differences in diastolic function between patients with amyloidosis
      and controls. Pulsed-wave Doppler echocardiography of transmitral flow was
      measured in 13 patients with amyloid heart disease and 13 age- and gender matched
      controls. E- waves (2 to 3 per subject) were analyzed using in-house developed
      software. Nine PDF-derived parameters were obtained in addition to conventional
      echocardiographic parameters of diastolic function. Compared to controls, cardiac
      amyloidosis patients had a larger left atrial area (23.7 +/- 7.5 cm2 vs. 18.5 +/-
      4.8 cm2, p = 0.04), greater interventricular septum wall thickness (14.4 +/- 2.6
      mm vs. 9.3 +/- 1.3 mm, p < 0.001), lower e' (0.06 +/- 0.02 m/s vs. 0.09 +/- 0.02
      m/s, p < 0.001) and higher E/e' (18.0 +/- 12.9 vs. 7.7 +/- 1.3, p = 0.001). The
      PDF parameter peak resistive force was greater in cardiac amyloidosis patients
      compared to controls (17.9 +/- 5.7 mN vs. 13.1 +/- 3.1 mN, p = 0.03), and other
      PDF parameters did not differ. PDF analysis revealed that patients with cardiac
      amyloidosis had a greater peak resistive force compared to controls, consistent
      with a greater degree of diastolic dysfunction. PDF analysis may be useful in
      characterizing diastolic function in amyloid heart disease.

PMID- 28433440
TI  - Spatial Compounding Technique to Obtain Rotation Elastogram: A Feasibility Study.
AB  - The perception of stiffness and slipperiness of a breast mass on palpation is
      used by physicians to assess the level of suspicion of a lesion as being
      malignant or benign. However, most current ultrasound elastography imaging
      methods provide only stiffness-related information. There is no existing approach
      that provides information about the local rigid body rotation undergone by only a
      loosely bonded, asymmetrically oriented lesion subjected to a small quasi-static
      compression. The inherent poor lateral resolution in ultrasound imaging poses a
      limitation in estimating the local rigid body rotation. Several techniques have
      been reported in the literature to improve the lateral resolution in ultrasound
      imaging, and among them is spatial compounding. In this study, we explore the
      feasibility of obtaining better-quality rotation elastograms with spatial
      compounding through simulations using Field II and experiments on tissue
      mimicking phantoms. The phantom was subjected to axial compression (~1%-2%) from
      the top, and the angular axial and lateral displacement estimates were obtained
      using a multilevel 2-D displacement tracking algorithm at different
      insonification angles. A rotation elastogram (RE) was obtained by taking half of
      the difference between the lateral gradient of the axial displacement estimates
      and the axial gradient of the lateral displacement estimates. Contrast-to-noise
      ratio was used to quantify the improvements in quality of RE. Contrast-to-noise
      ratio values were calculated by varying the maximum steering angle and the
      incremental angle, and its effects on RE quality were evaluated. Both simulation
      and experimental results corroborated and indicated a significant improvement in
      the quality of RE using compounding technique.

PMID- 28433441
TI  - Role of Contrast-Enhanced Ultrasound in Diagnosis of Thyroid Nodules in Acoustic
      Radiation Force Impulse "Gray Zone".
AB  - The aim of this study was to evaluate the clinical value of contrast-enhanced
      ultrasound (CEUS) in the diagnosis of thyroid nodules in the acoustic radiation
      force impulse (ARFI) "gray zone" (the shear wave velocity is in the range 2.5-3
      m/s). ARFI was performed before thyroidectomy in 70 patients with 200 thyroid
      nodules, and then CEUS was performed in 40 thyroid nodules in the "gray zone."
      The accuracy of ARFI for the 200 thyroid nodules was 82% (164/200). The accuracy
      of ARFI for the 40 "gray zone" thyroid nodules was 70% (28/40), whereas the
      accuracy of CEUS for the "gray zone" thyroid nodules was 90% (36/40). There was a
      significant difference in accuracy (p < 0.05). CEUS has better accuracy for
      thyroid nodules in the ARFI "gray zone." CEUS supplemented ARFI in differential
      diagnosis of benign and malignant thyroid nodules.

PMID- 28433442
TI  - Strabismus and mental disorders among Israeli adolescents.
AB  - PURPOSE: To assess the association between strabismus and mental disorders in
      adolescents. METHODS: This case-control study included 662,641 Israeli teenagers
      that underwent medical evaluation by the Israel Defense Force as part of the
      preconscription assessment between 2005 and 2013. The association between common
      mental disorders (anxiety disorder, mood disorder, adjustment disorder, and
      attention deficit hyperactivity disorder [ADHD]) and either uncorrected
      strabismus or corrected strabismus was examined. The association with strabismus
      correction was assessed by the differences between the corrected and uncorrected
      groups. RESULTS: The mean age at the time of the examination was 17.3 +/- 0.53
      years, with a male predominance (59%). A total of 1,598 subjects (0.24%) had
      strabismus. Of those, 952 (60%) underwent successful correction and 646 (40%) did
      not undergo successful correction. A significant association was found between
      uncorrected strabismus and anxiety disorders (OR = 1.91; 95% CI = 1.02-3.57; P =
      0.047) and between corrected strabismus and ADHD (OR = 2.62; 95% CI = 1.18-5.87;
      P = 0.03). Strabismus correction (as assessed by comparing the uncorrected and
      corrected strabismus groups) was not significantly associated with the mental
      disorders we examined, but a nearly statistically significant association with
      anxiety disorder was observed (OR = 2.978; 95% CI, 1.013-8.754; P = 0.06).
      CONCLUSIONS: The evidence from our cohort suggests that strabismus correction,
      even in the absence of visual impairment, is not associated with mental disorders
      examined in this study.

PMID- 28433443
TI  - Arthroscopic Debridement Versus Platelet-Rich Plasma Injection: A Prospective,
      Randomized, Comparative Study of Chronic Lateral Epicondylitis With a Nearly 2
      Year Follow-Up.
AB  - PURPOSE: The purpose of this prospective, randomized study was to compare the
      efficacy of autologous platelet-rich plasma (PRP) injections and arthroscopic
      lateral release in treating chronic lateral epicondylitis (LE). METHODS: Patients
      who had a clinical diagnosis of LE confirmed by ultrasound (US) were included in
      this study. A total of 101 patients received arthroscopic release (n = 50) or US
      guided PRP injections (n = 51). Outcomes were assessed using a visual analog
      scale for pain, the Patient-Rated Tennis Elbow Evaluation (PRTEE), and a
      calibrated hand dynamometer for grip strength. RESULTS: Both patient groups
      experienced significant improvement in all measures. Between-group comparisons
      showed a significantly higher value in the PRP group only for grip strength at
      week 8 (P = .0073); all other significant differences were in favor of
      arthroscopy: overall pain (P = .0021), night pain (P = .0013), and PRTEE score (P
      = .0013) at week 104 and grip strength at weeks 24, 52, and 104 (all P < .0001).
      Consumption of rescue pain medication was not significantly different between the
      groups. CONCLUSIONS: The present findings suggest that (1) PRP injections and
      arthroscopic extensor carpi radialis brevis release are both effective in the
      short and medium term; (2) PRP patients experienced a significant worsening of
      pain at 2 years; (3) arthroscopic release ensured better long-term outcomes in
      terms of pain relief and grip strength recovery; and (4) both procedures were
      safe and well accepted by patients. LEVEL OF EVIDENCE: Level II, prospective
      comparative study.

PMID- 28433445
TI  - Parapapillary Choroidal Microvasculature Dropout in Glaucoma: A Comparison
      between Optical Coherence Tomography Angiography and Indocyanine Green
      Angiography.
AB  - PURPOSE: To investigate whether the parapapillary choroidal microvasculature
      dropout (MvD) determined by optical coherence tomography angiography (OCTA) in
      glaucomatous eyes indicates a true perfusion defect and whether the MvD
      accurately represents the area of nonperfusion. DESIGN: Observational case
      series. PARTICIPANTS: Thirty primary open-angle glaucoma (POAG) patients with
      choroidal MvD as determined by OCTA and 13 POAG patients without this dropout.
      METHODS: Peripapillary circulation was evaluated using both OCTA and indocyanine
      green angiography (ICGA). For OCTA, the choroidal microvasculature was evaluated
      using 4.5*4.5-mm choroid-disc vessel density maps of OCTA images of the optic
      nerve head. An MvD was identified in OCTA by the presence of a capillary dropout.
      A filling defect observed in ICGA was defined as a perfusion defect (ICGPD). MAIN
      OUTCOME MEASURES: The topographic correlations between MvD and ICGPD determined
      based on their circumferential extent, location, and area. RESULTS: The ICGPD was
      observed as a sectoral filling defect in the 30 POAG patients exhibiting MvD and
      appeared identical to the MvD in terms of the shape and location. The
      circumferential extent, location, and area of ICGPD did not differ from those of
      the MvD (all P > 0.05). The ICGPD was not found in any of the eyes not having the
      MvD. CONCLUSIONS: A localized MvD observed in the parapapillary choroid using
      OCTA coincided with the ICGPD detected by ICGA. These findings indicate that OCTA
      accurately images impaired parapapillary choroidal circulation.

PMID- 28433444
TI  - Risk of Ocular Hypertension in Adults with Noninfectious Uveitis.
AB  - PURPOSE: To describe the risk and risk factors for ocular hypertension (OHT) in
      adults with noninfectious uveitis. DESIGN: Retrospective, multicenter, cohort
      study. PARTICIPANTS: Patients aged >=18 years with noninfectious uveitis seen
      between 1979 and 2007 at 5 tertiary uveitis clinics. METHODS: Demographic,
      ocular, and treatment data were extracted from medical records of uveitis cases.
      MAIN OUTCOME MEASURES: Prevalent and incident OHT with intraocular pressures
      (IOPs) of >=21 mmHg, >=30 mmHg, and increase of >=10 mmHg from documented IOP
      recordings (or use of treatment for OHT). RESULTS: Among 5270 uveitic eyes of
      3308 patients followed for OHT, the mean annual incidence rates for OHT >=21 mmHg
      and OHT >=30 mmHg are 14.4% (95% confidence interval [CI], 13.4-15.5) and 5.1%
      (95% CI, 4.7-5.6) per year, respectively. Statistically significant risk factors
      for incident OHT >=30 mmHg included systemic hypertension (adjusted hazard ratio
      [aHR], 1.29); worse presenting visual acuity (<=20/200 vs. >=20/40, aHR, 1.47);
      pars plana vitrectomy (aHR, 1.87); history of OHT in the other eye: IOP >=21 mmHg
      (aHR, 2.68), >=30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or
      surgery in the other eye (aHR, 4.17); anterior chamber cells: 1+ (aHR, 1.43) and
      >=2+ (aHR, 1.59) vs. none; epiretinal membrane (aHR, 1.25); peripheral anterior
      synechiae (aHR, 1.81); current use of prednisone >7.5 mg/day (aHR, 1.86);
      periocular corticosteroids in the last 3 months (aHR, 2.23); current topical
      corticosteroid use [>=8*/day vs. none] (aHR, 2.58); and prior use of fluocinolone
      acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous
      hypotony (aHR, 0.43) were associated with statistically significantly lower risk
      of OHT. CONCLUSIONS: Ocular hypertension is sufficiently common in eyes treated
      for uveitis that surveillance for OHT is essential at all visits for all cases.
      Patients with 1 or more of the several risk factors identified are at
      particularly high risk and must be carefully managed. Modifiable risk factors,
      such as use of corticosteroids, suggest opportunities to reduce OHT risk within
      the constraints of the overriding need to control the primary ocular inflammatory
      disease.

PMID- 28433446
TI  - Functional Magnetic Resonance Imaging to Assess the Neurobehavioral Impact of
      Dysphotopsia with Multifocal Intraocular Lenses.
AB  - PURPOSE: To investigate the association between dysphotopsia and neural responses
      in visual and higher-level cortical regions in patients who recently received
      multifocal intraocular lens (IOL) implants. DESIGN: Cross-sectional study.
      PARTICIPANTS: Thirty patients 3 to 4 weeks after bilateral cataract surgery with
      diffractive IOL implantation and 15 age- and gender-matched control subjects.
      METHODS: Functional magnetic resonance imaging (fMRI) was performed when
      participants viewed low-contrast grating stimuli. A light source surrounded the
      stimuli in half of the runs to induce disability glare. Visual acuity, wavefront
      analysis, Quality of Vision (QoV) questionnaire, and psychophysical assessment
      were performed. MAIN OUTCOME MEASURES: Cortical activity (blood oxygen level
      dependent [BOLD] signal) in the primary visual cortex and in higher-level brain
      areas, including the attention network. RESULTS: When viewing low-contrast
      stimuli under glare, patients showed significant activation of the effort-related
      attention network in the early postoperative period, involving the frontal,
      middle frontal, parietal frontal, and postcentral gyrus (multisubject random
      effects general linear model (GLM), P < 0.03). In contrast, controls showed only
      relative deactivation (due to lower visibility) of visual areas (occipital lobe
      and middle occipital gyrus, P < 0.03). Patients also had relatively stronger
      recruitment of cortical areas involved in learning (anterior cingulate gyrus),
      task planning, and solving (caudate body). Patients reporting greater symptoms
      induced by dysphotic symptoms showed significantly increased activity in several
      regions in frontoparietal circuits, as well as cingulate gyrus and caudate
      nucleus (q < 0.05). We found no correlation between QoV questionnaire scores and
      optical properties (total and higher order aberration, modulation transfer
      function, and Strehl ratio). CONCLUSIONS: This study shows the association
      between patient-reported subjective difficulties and fMRI outcomes, independent
      of optical parameters and psychophysical performance. The increased activity of
      cortical areas dedicated to attention (frontoparietal circuits), to learning and
      cognitive control (cingulate), and to task goals (caudate) likely represents the
      beginning of the neuroadaptation process to multifocal IOLs.

PMID- 28433447
TI  - Impaired fasting glucose predicts the development of hypertension over 6years in
      female adults: Results from the rural Chinese cohort study.
AB  - AIMS: To investigate whether impaired fasting glucose (IFG) is an independent
      risk factor for incident hypertension in a rural Chinese population. METHODS: We
      selected 9583 eligible participants 18 to 75years old, who were without
      hypertension and diabetes at baseline (from 2007 to 2008) and were from a rural
      area in the middle of China. Concentration of fasting glucose at baseline was
      assessed in quartiles to predict hypertension risk by gender. Odds ratios (ORs)
      and 95% confidence intervals (CIs) for IFG (fasting glucose of 100 to 125mg/dl)
      associated with hypertension were estimated by logistic regression models.
      RESULTS: Risk of hypertension was increased for females with glucose levels in
      quartile 2 (90-96mg/dl), quartile 3 (96-102mg/dl), and quartile 4 (102-125mg/dl)
      versus quartile 1 (<90mg/dl): OR=1.27 (95% CI=1.01-1.60), 1.30 (1.04-1.63), and
      1.55 (1.24-1.93), respectively. During the 6-year follow-up, the cumulative
      incidence of hypertension was greater for people with IFG than normal fasting
      glucose (NFG) at baseline (23.9% vs 18.4%, p<0.001 for males and 23.8% vs 16.4%,
      p<0.001 for females). Risk of incident hypertension was significantly increased
      for females with IFG versus NFG (OR=1.23 95% CI=1.05-1.45). CONCLUSIONS: IFG may
      be an independent risk factor for hypertension in normotensive nondiabetic
      Chinese females.

PMID- 28433448
TI  - Anemia complicating type 2 diabetes: Prevalence, risk factors and prognosis.
AB  - AIMS: To determine the prevalence, risk factors and prognosis of anemia in
      representative community-based patients with type 2 diabetes. METHODS: Data from
      the Fremantle Diabetes Study Phase II (FDS2; n=1551, mean age 65.7years, 51.9%
      males) and Busselton Diabetes Study (BDS; n=186, mean age 70.2years, 50.0% males)
      cohorts, and from 186 matched BDS participants without diabetes, were analyzed.
      The prevalence of anemia (hemoglobin <=130g/L males, <=120g/L females) was
      determined in each sample. In FDS2, associates of anemia were assessed using
      multiple logistic regression and Cox proportional hazards modeling identified
      predictors of death during 4.3+/-1.2years post-recruitment. RESULTS: The
      prevalence of anemia at baseline was 11.5% in FDS2 participants, 17.8% in BDS
      type 2 patients and 5.4% in BDS participants without diabetes. In FDS2, 163 of
      178 patients with anemia (91.6%) had at least one other risk factor (serum
      vitamin B12<140pmol/L, serum ferritin <30MUg/L and/or transferrin saturation<20%,
      serum testosterone <10nmol/L (males), glitazone therapy, estimated glomerular
      filtration rate (eGFR) <60mL/min 1.73m2, malignancy, hemoglobinopathy). More
      anemic than non-anemic FDS2 patients died (28.7% versus 8.0%; P<0.001). After
      adjustment for other independent predictors (age as time-scale, male sex,
      Aboriginality, marital status, smoking, eGFR), anemia was associated with a 57%
      increase in mortality (P=0.015). CONCLUSIONS: Type 2 diabetes at least doubles
      the risk of anemia but other mostly modifiable risk factors are usually present.
      Anemia is associated with an increased risk of death after adjustment for other
      predictors.

PMID- 28433450
TI  - A retrospective cohort study of concomitant ipsilateral extra-capsular and intra
      capsular fractures of the proximal femur. Are they casual findings or an
      undervalued reality?
AB  - BACKGROUND: Fractures of the proximal femur constitute a major public health
      problem, with an annual incidence in Spain of 7.6 cases per 1000 inhabitants over
      65 years of age. Hip fractures are frequent in elderly patients, related to
      osteoporosis and with low energy trauma, which means that they can be considered
      a geriatric syndrome. Simultaneous ipsilateral extra- and intra-articular hip
      fractures are considered as very rare are, and generally speaking, classified as
      extra- or intra-capsular fractures. Moreover, there is no consensus with regard
      to treatment of these concomitant fractures. AIM: To estimate the incidence of
      concomitant ipsilateral extra- and intra-capsular fractures of the proximal
      femur, and to describe the diagnostic process and the clinical characteristics of
      these concomitant fractures. PATIENTS AND METHODS: Retrospective cohort study of
      patients with hip fractures. The incidence of combined extra- and intra-capsular
      fractures was estimated, a confidence interval of 95% (95%CI) was calculated and
      a descriptive analysis was drawn up. RESULTS: Between May 2010 (the date on which
      the Orthopaedic and Trauma Surgery Department of our new Hospital began the
      surgical activity) and December 2016, 33 (median age, 86 years-old) of the 2625
      hip fractures were classified as simultaneous extra- and intra-capsular
      ipsilateral fractures. The overall cumulative incidence was of 1.3% (95%CI:0.9
      1.8%). In 32 (97%) of the patients, the fracture was a consequence of a low
      energy trauma (ground level fall), while the remainder was due to a medium energy
      trauma (skating). In all cases the two fracture lines seem to be independent of
      each other, which suggests different mechanisms of injury from that of isolated
      subcapital or intrertrochanteric fracture. CONCLUSION: The incidence of
      concomitant ipsilateral extra- and intra-capsular fractures of the proximal femur
      must be taken into account in patients over 65 years of age. It is clinically
      relevant to identify these concomitant fractures in order to arrive at a correct
      diagnosis, which will facilitate preoperative planning and the choice of the best
      treatment to achieve a better outcome. Misdiagnosis may cause further problems,
      such as fixation failures, disability and, in a worst case scenario, an increased
      risk of death. Therefore, a good and complete preoperative study is important,
      along with both good quality X-ray projections and 2D and 3D Ct-Scans in case of
      doubt.

PMID- 28433449
TI  - Diabetes, depressive symptoms, and functional disability in African Americans:
      the Jackson Heart Study.
AB  - AIMS: To investigate the degree to which comorbid depression contributes to the
      relationship of diabetes with functional disability in African Americans (AAs), a
      population at high-risk for complications. METHODS: We examined 2989 African
      Americans (AAs) in the Jackson Heart Study who had diabetes and depressive
      symptoms (CES-D) assessed at baseline. Overall functional disability was defined
      as the inability to perform at least one task of daily living. Multivariable
      logistic regression models explored the association of diabetes and depressive
      symptoms with functional disability. RESULTS: Prevalence of overall functional
      disability was highest with both diabetes and depressive symptoms (54%), similar
      with diabetes alone (31%) or depressive symptoms alone (33%), and lowest with
      neither (15%). Adjusting for demographics, smoking, BMI, cardiovascular
      comorbidities, and hsCRP, the association of depressive symptoms alone
      (OR=2.30,95% CI 1.75-3.03) and both diabetes and depressive symptoms
      (OR=2.75,1.88-4.04) with overall functional disability was significant, but not
      for diabetes alone (OR=1.26,0.95-1.67), compared to neither. In regression
      analyses including any diabetes and any depressive symptoms together in models,
      the main effect of depressive symptoms but not diabetes was associated with
      overall functional disability, and the interaction term was not significant (p
      value=0.84). CONCLUSIONS: Functional disability was highest among AAs who have
      both diabetes and depressive symptoms; the latter was a stronger contributor.
      Future studies should explore mechanisms underlying functional disability in
      diabetes, particularly the role of depression.

PMID- 28433451
TI  - Prospective randomized study comparing two cephalomedullary nails for elderly
      intertrochanteric fractures: Zimmer natural nail versus proximal femoral nail
      antirotation II.
AB  - OBJECTIVES: Although both clinical and biomechanical studies suggest that
      cephalomedullary implants have a mechanical advantage over extramedullary
      implants, a high rate of complications or implant failure remains in elderly
      patients with osteoporosis. In an attempt to address some of these challenges,
      new implants with improved designs named proximal femoral nail antirotation II
      (PFNA II) and Zimmer natural nail (ZNN) were developed for elderly patients.
      Although the PFNA II reportedly has good clinical outcomes, it is unclear which
      implant achieves better safety and efficacy for treating intertrochanteric hip
      fractures. The primary objective of this prospective, randomized trial involved
      353 patients was to evaluate Harris Hip Score (HHS). The secondary objective was
      to compare results associated with clinical outcome such as operation time,
      fluoroscopy time, lateral hip pain, walking ability, and reoperation rate as well
      as the incidence of cut-out by using implant position and fracture reduction
      quality. METHODS: 353 patients with an intertrochanteric fracture amenable to
      either ZNN implant or PFNA II with a mean age of 77.0 years and a mean follow-up
      period of 12.3 months were included. We analyzed 353 patients with an
      intertrochanteric fracture treated using a ZNN implant (n=172, group I) or a PFNA
      II (n=181, group II) between January 2011 and August 2014. RESULTS: There were no
      significant inter-group differences in HHS, walking ability, and reoperation rate
      were observed. However, operation and fluoroscopy time were significantly
      different between the two groups as well as group I showed a higher incidence of
      lateral hip pain than group II. In addition, no significant inter-group
      differences in cut-out rate determined by implant position and fracture reduction
      quality. We also found that cut-out was associated with lag screw position in the
      femoral head measured by Tip-apex distance (TAD) but not with reduction quality.
      CONCLUSIONS: Although group I had significant longer operation and fluoroscopy
      time than group II, both implants are useful tools in the treatment of elderly
      intertrochanteric fractures as well as only TAD, but not Cleveland zone
      significantly correlated with lag screw cut-out.

PMID- 28433452
TI  - The timing of chest compressions and artificial ventilation: A re-appraisal.

PMID- 28433453
TI  - Attending documentation contribution to billing at an academic ED with an
      electronic health record.
AB  - INTRODUCTION: In emergency medicine (EM), patient care documentation serves many
      functions, including supporting reimbursement. In addition, many electronic
      health record systems facilitate automatically populating certain data fields. As
      a result, in the academic model, the attending's note may now more often
      recapitulate many of the same elements found in the resident's or physician
      assistant's (PA) note. We sought to determine the value of additional attending
      documentation, and how often the attending documentation prevented a downcoding
      event. METHODS: This retrospective, cross-sectional study was exempted by the
      Institutional Review Board. We randomly reviewed 10 charts for each attending
      physician during the study period. Outcome measures included the frequency of
      prevented downcoding events, and the difference in this incidence between
      residents and PAs. RESULTS: 530 charts were identified, but 6 were excluded as
      these patients left without being seen. 524 charts remained, of which 286 (45%)
      notes were written by residents and 238 (55%) notes were written by PAs.
      Attending documentation prevented 16 (3%) downcoding events, of which 11 were in
      patient encounters documented by residents and 5 were in encounters documented by
      PAs (p=0.057). CONCLUSIONS: In this study of an academic medical center
      documentation model with an EHR, EM attending documentation of the history of
      present illness, review of systems, physical exam, and medical decision making
      portions prevented downcoding in a small number of cases. In addition, there was
      no significant difference in the incidence of prevented downcoding events between
      residents and PAs.

PMID- 28433454
TI  - A randomized comparison of three chest compression techniques and associated
      hemodynamic effect during infant CPR: A randomized manikin study.
AB  - INTRODUCTION: Pediatric cardiac arrest is an uncommon but critical life
      threatening event requiring effective cardiopulmonary resuscitation. High-quality
      cardio-pulmonary resuscitation (CPR) is essential, but is poorly performed, even
      by highly skilled healthcare providers. The recently described two-thumb chest
      compression technique (nTTT) consists of the two thumbs directed at the angle of
      90 degrees  to the chest while having the fingers fist-clenched. This technique
      might facilitate adequate chest-compression depth, chest-compression rate and
      rate of full chest-pressure relief. METHODS: 42 paramedics from the national
      Emergency Medical Service of Poland performed three single-rescuer CPR sessions
      for 10 minutes each. Each session was randomly assigned to the conventional two
      thumb (TTHT), the conventional two-finger (TFT) or the nTTT. The manikin used for
      this study was connected with an arterial blood pressure measurement device and
      blood measurements were documented on a 10-seconds cycle. RESULTS: The nTTT
      provided significant higher systolic (82 vs. 30 vs. 41 mmHg). A statistically
      significant difference was noticed between nTTT and TFT (p<.001), nTTT and TTHT
      (p<0.001), TFT and TTHT (p=0.003). The median diastolic preassure using nTTT was
      16 mmHg compared with 9 mmHg for TFT (p<0.001), and 9.5 mmHg for TTHT (p<0.001).
      Mean arterial pressure using distinct methods varied and amounted to 40 vs. 22.
      vs. 26 mmHg (nTTT vs. TFT vs. TTHT, respectively). A statistically significant
      difference was noticed between nTTT and TFT (p<0.001), nTTT and TTEHT (p<0.001),
      and TFT and TTHT (p<0.001). The highest median pulse pressure was obtained by the
      nTTT 67.5 mmHg. Pulse pressure was 31.5 mmHg in the TTHT and 24 mmHg in the TFT.
      The difference between TFT and TTHT (p=0.025), TFT and nTTT (p<0.001), as well as
      between TTHT and nTTT (p<0.001) were statistically significant. CONCLUSIONS: The
      new nTTT technique generated higher arterial blood pressures compared to
      established chest compression techniques using an infant manikin model,
      suggesting a more effective chest compression. Our results have important
      clinical implications as nTTT was simple to perform and could be widely taught to
      both healthcare professionals and bystanders. Whether this technique translates
      to improved outcomes over existing techniques needs further animal studies and
      subsequent human trials.

PMID- 28433455
TI  - Peritoneal fluid localization on FAST examination in the pediatric trauma
      patient.
AB  - OBJECTIVE: To determine the location of intraperitoneal free fluid on FAST exam
      in pediatric patients undergoing evaluation for trauma. METHODS: Retrospective
      review of all FAST exams positive for intraperitoneal free fluid performed in
      patients sustaining trauma between August 2009 and February 2016 in an urban
      pediatric emergency department. Positive results were categorized into one of
      nine potential intraperitoneal locations; 4 each in the right and left upper
      quadrants, and the pelvis. RESULTS: One hundred and three complete positive
      studies were reviewed. The median age of patients was 10years (IQR 7-14) with 66%
      being male. Ninety-five percent had fluid present in the pelvis, 35% had fluid
      present in the RUQ, and 16.5% had fluid present in the LUQ. Overall, the most
      frequent location of fluid outside of the pelvis was found at the inferior tip of
      the liver, present in 83.3% of patients with fluid in the RUQ and 29% of all
      patients with a positive FAST. CONCLUSIONS: The majority of pediatric trauma
      patients with a positive FAST exam will exhibit free fluid in the pelvis.
      Particular attention should be directed to the inferior tip of the liver in
      children as this represents the most common location for fluid collection outside
      the pelvis.

PMID- 28433456
TI  - Cytokine alterations and cognitive impairment in major depressive disorder: From
      putative mechanisms to novel treatment targets.
AB  - Overwhelming evidence indicates the involvement of immune-inflammatory processes
      in the pathophysiology of major depressive disorder (MDD). Peripheral cytokine
      alterations serve as one of most consistently reported indices of subthreshold
      inflammatory state observed in MDD. Although cytokines cannot pass directly
      through the blood-brain barrier, a number of transport mechanisms have been
      reported. In addition, peripheral cytokines may impact central nervous system via
      downstream effectors of their biological activity. Animal model studies have
      provided evidence that cytokines might impact cognitive performance through
      direct and indirect effects on long-term potentiation, neurogenesis and synaptic
      plasticity. Therefore, it has been hypothesized that cytokine alterations might
      contribute to cognitive impairment that is widely observed in MDD and persists
      beyond episodes of acute relapse in the majority of patients. Although several
      studies have provided that peripheral cytokine alterations might be related to
      cognitive deficits in patients with MDD, the quality of evidence still leaves
      much to be desired due to methodological heterogeneity and limitations. In this
      article, we provide an overview of studies investigating the association between
      peripheral cytokine alterations and cognitive performance in MDD, discuss
      underlying mechanisms and neural substrates. Finally, we propose possible
      treatment targets related to cytokine alterations taking into account existing
      evidence for antidepressant efficacy of anti-inflammatory pharmacological
      treatment modalities.

PMID- 28433457
TI  - Spatial and temporal expression patterns of genes around nine neuroticism
      associated loci.
AB  - Neuroticism is a high-order personality trait. Individuals with higher
      neuroticism have increased risks of various psychiatric disorders and physical
      health outcomes. Neuroticism is related to physiological differences in the
      brain. A recent genome-wide association study identified nine distinct genomic
      loci that contribute to neuroticism. Brain development and function depend on the
      precise regulation of gene expression, which is differentially regulated across
      brain regions and developmental stages. Using multiple publicly available human
      post-mortem databases, we investigated, in brain and non-brain tissues and across
      several developmental life stages, the spatial and temporal expression patterns
      of genes arising from nine neuroticism-associated loci. Functional gene-network
      analysis for neuroticism-associated genes was performed. The spatial expression
      analysis revealed that the nearest genes (GRIK3, SRP9, KLHL2, PTPRD, ELAVL2,
      CRHR1 and CELF4) from index single-nucleotide polymorphisms (SNPs) at the nine
      loci were intensively enriched in the brain compared with their representation in
      non-brain tissues (p<1.56*10-3). The nearest genes associated with the glutamate
      receptor activity network consisted mainly of GRIK3 (FDR q=4.25*10-2). The
      temporal expression analysis revealed that the neuroticism-associated genes were
      divided into three expression patterns: KLHL2, CELF4 and CRHR1 were
      preferentially expressed during postnatal stages; PTPRD, ELAVL2 and MFHAS1 were
      expressed during prenatal stages; and the other three genes were not expressed
      during specific life stages. These findings suggest that the glutamate network
      might be a target for investigating the neurobiological mechanisms underlying
      susceptibilities to higher neuroticism and several psychiatric disorders and that
      neuroticism is mediated by genes specifically expressed in the brain during
      several developmental stages.

PMID- 28433458
TI  - Linking the biological underpinnings of depression: Role of mitochondria
      interactions with melatonin, inflammation, sirtuins, tryptophan catabolites, DNA
      repair and oxidative and nitrosative stress, with consequences for classification
      and cognition.
AB  - The pathophysiological underpinnings of neuroprogressive processes in recurrent
      major depressive disorder (rMDD) are reviewed. A wide array of biochemical
      processes underlie MDD presentations and their shift to a recurrent,
      neuroprogressive course, including: increased immune-inflammation, tryptophan
      catabolites (TRYCATs), mitochondrial dysfunction, aryl hydrocarbonn receptor
      activation, and oxidative and nitrosative stress (O&NS), as well as decreased
      sirtuins and melatonergic pathway activity. These biochemical changes may have
      their roots in central, systemic and/or peripheral sites, including in the gut,
      as well as in developmental processes, such as prenatal stressors and
      breastfeeding consequences. Consequently, conceptualizations of MDD have
      dramatically moved from simple psychological and central biochemical models, such
      as lowered brain serotonin, to a conceptualization that incorporates whole body
      processes over a lifespan developmental timescale. However, important hubs are
      proposed, including the gut-brain axis, and mitochondrial functioning, which may
      provide achievable common treatment targets despite considerable inter-individual
      variability in biochemical changes. This provides a more realistic model of the
      complexity of MDD and the pathophysiological processes that underpin the shift to
      rMDD and consequent cognitive deficits. Such accumulating data on the
      pathophysiological processes underpinning MDD highlights the need in psychiatry
      to shift to a classification system that is based on biochemical processes,
      rather than subjective phenomenology.

PMID- 28433459
TI  - Depressive disorders: Processes leading to neurogeneration and potential novel
      treatments.
AB  - Mood disorders are wide spread with estimates that one in seven of the population
      are affected at some time in their life (Kessler et al., 2012). Many of those
      affected with severe depressive disorders have cognitive deficits which may
      progress to frank neurodegeneration. There are several peripheral markers shown
      by patients who have cognitive deficits that could represent causative factors
      and could potentially serve as guides to the prevention or even treatment of
      neurodegeneration. Circadian rhythm misalignment, immune dysfunction and
      oxidative stress are key pathologic processes implicated in neurodegeneration and
      cognitive dysfunction in depressive disorders. Novel treatments targeting these
      pathways may therefore potentially improve patient outcomes whereby the primary
      mechanism of action is outside of the monoaminergic system. Moreover, targeting
      immune dysfunction, oxidative stress and circadian rhythm misalignment (rather
      than primarily the monoaminergic system) may hold promise for truly disease
      modifying treatments that may prevent neurodegeneration rather than simply
      alleviating symptoms with no curative intent. Further research is required to
      more comprehensively understand the contributions of these pathways to the
      pathophysiology of depressive disorders to allow for disease modifying treatments
      to be discovered.

PMID- 28433460
TI  - Stimulatory effect of desipramine on lung metastases of adenocarcinoma MADB 106
      in stress highly-sensitive and stress non-reactive rats.
AB  - The effect of antidepressant drugs on tumor progress is very poorly recognized.
      The aim of the present study was to examine the effect of individual reactivity
      to stress and 24-day desipramine (DES) administration on the metastatic
      colonization of adenocarcinoma MADB 106 cells in the lungs of Wistar rats. Wistar
      rats were subjected to stress procedure according to the chronic mild stress
      (CMS) model of depression for two weeks and stress highly-sensitive (SHS) and
      stress non-reactive (SNR) rats were selected. SHS rats were more prone to cancer
      metastasis than SNR ones and chronic DES treatment further increased the number
      of lung metastases by 59% and 50% in comparison to vehicle-treated appropriate
      control rats. The increase in lung metastases was connected with DES-induced skew
      macrophage activity towards M2 functional phenotype in SHS and SNR rats.
      Moreover, during 24h after DES injection in healthy rats, the decreased number of
      TCD8+ and B cells in SHS and SNR rats as well as NK cell cytotoxic activity in
      SNR rats could be attributed to the lowered capacity to defend against cancer
      metastasis observed in chronic DES treated and tumor injected rats.

PMID- 28433461
TI  - Severely impaired adult brain neurogenesis in cyclin D2 knock-out mice produces
      very limited phenotypic changes.
AB  - The discovery of new neurons being produced in the brains of adult mammals (adult
      brain neurogenesis) began a quest to determine the function(s) of these cells.
      Major hypotheses in the field have assumed that these neurons play pivotal role,
      in particular, in learning and memory phenomena, mood control, and
      epileptogenesis. In our studies summarized herein, we used cyclin D2 knockout
      (KO) mice, as we have shown that cyclin D2 is the key factor in adult brain
      neurogenesis and thus its lack produces profound impairment of the process. On
      the other hand, developmental neurogenesis responsible for the brain formation
      depends only slightly on cyclin D2, as the mutants display minor structural
      abnormalities, such as smaller hippocampus and more severe disturbances in the
      structure of the olfactory bulbs. Surprisingly, the studies have revealed that
      cyclin D2 KO mice did not show major deficits in several behavioral paradigms
      assessing hippocampal learning and memory. Furthermore, missing adult brain
      neurogenesis affected neither action of antidepressants, nor epileptogenesis. On
      the other hand, minor deficits observed in cyclin D2 KO mice in fine tuning of
      cognitive functions, species-typical behaviors and alcohol consumption might be
      explained by a reduced hippocampal size and/or other developmentally driven brain
      impairments observed in these mutant mice. In aggregate, surprisingly, missing
      almost entirely adult brain neurogenesis produces only very limited behavioral
      phenotype that could be attributed to the consequences of the development
      dependent minor brain abnormalities.

PMID- 28433462
TI  - [Health and access to health care of 18-25 years old people not in employment,
      education or training (NEETs) attending the French 'missions locales'].
AB  - BACKGROUND: In France, "missions locales" are public assistance units for young
      people aged 16-25 years not in employment, education or training (NEET). The
      health status of the more than 1.5 million young adults attending these units
      annually is unknown. The purpose of this study was to describe the health status
      and health care use of this population in comparison with the general population
      of the same age. METHODS: The Presaje survey was conducted in 2011 on a
      randomized sample of 1453 young adults aged 18-25 years who attended five
      "missions locales" in mainland France. Data were analyzed and compared with those
      of participants of the same age interviewed in a French national health survey
      (Barometre Sante 2010, n=2899) and in a regional cohort (SIRS, n=204) conducted
      in the Greater Paris area, both in 2010. RESULTS: The overall social profiles of
      this NEET population was diverse, but with globally more difficult living
      conditions than in the general population. Health-related vulnerability factors
      identified were: insufficient health insurance; low educational level; numerous
      adverse experiences during childhood and social isolation. Some of their health
      indicators were remarkably poor in comparison with participants in the Barometre
      sante study: 19.2 % (CI95 %=[17.2-21.3]) had a chronic disease-versus 8.2 % (CI95
      %=[7.0-9.4]) (P<0.001); 31.9 % (CI95 %=[26.8-37.4]) were overweight or obese
      versus 17.9 % (CI95 %=[16.3-19.6]) (P<0.001) and 19.6 % (CI95 %=[15.2-23.9]) were
      depressed-versus 7.3 %(CI95 %=[3.8-10.9]) (P<0.001). Compared with participants
      of the SIRS survey, fewer (70.4 %) (CI95 %=[68.0-72.7]) had a family doctor
      versus 79.7 % (CI95 %=[73.1-86.2]) (P<0.05). Among the women in the Presaje
      survey, 38.0 % [30.5-45.4] had a regular gynecological follow-up-versus 80.9 %
      (CI95 %=[71.5-90.4]) in the SIRS survey (P<0.001). CONCLUSION: Careful attention
      must be given to the young NEET population. Many of these youths are not familiar
      with health care services despite their important health care needs. Integrating
      health services into the "missions locales" may help detect health problems in
      this population, facilitating links to care.

PMID- 28433464
TI  - Electronic synoptic reporting: assessing the completeness of synoptic and
      narrative reports for Roux-en-Y gastric bypass.
AB  - BACKGROUND: Operative reporting is the foundation of surgical communication. The
      quality indicators (QIs) contained in these reports can be used to document the
      performance of processes that affect patient care and may afford quality
      assurance with improvement in healthcare. OBJECTIVES: We assessed the degree to
      which the electronic synoptic report (SR) documents the operative QIs compared
      with narrative reports (NR) for Roux-en-Y gastric bypass (RYGB). The time to
      report availability on patient chart was also identified as a secondary measure.
      SETTING: Academic center, public hospital, Canada. METHODS: A total of 40
      prospectively collected RYGB synoptic reports and 40 case-matched historical NRs
      were compared against checklist QIs that were established by a national Delphi
      process. These checklist QIs are validated and have high interrater agreement at
      our institution. Time from dictation to report availability on patient chart was
      measured. RESULTS: SR had a mean completion of 99.7% (+/-standard deviation [SD]
      1.3%) compared with 64.0% (+/-SD 6.3%) for NR (t = 36.0, P<.0001). All
      subsections of SR were>99% complete and significantly higher than NR (P<.001).
      The mean time from NR dictation to report availability was 4.14 days (SD+/-3.17,
      range 0-10 d). All SRs were in the operative area after the procedure and were
      available immediately. CONCLUSION: The RYGB synoptic report is superior to the
      narrative report for inclusion of accepted quality indicators and time to
      availability. Important elements, including process of care, demographic
      characteristics, and anatomic-related data, were often missing from the NR. SR is
      a promising method for improving documentation for RYGB.

PMID- 28433466
TI  - Orosensory responsiveness and alcohol behaviour.
AB  - Consumption of alcoholic beverages is widespread through much of the world, and
      significantly impacts human health and well-being. We sought to determine the
      contribution of orosensation ('taste') to several alcohol intake measures by
      examining general responsiveness to taste and somatosensory stimuli in a
      convenience sample of 435 adults recruited from six cohorts. Each cohort was
      divided into quantiles based on their responsiveness to sweet, sour, bitter,
      salty, umami, metallic, and astringent stimuli, and the resulting quantiles
      pooled for analysis (Kruskal-Wallis ANOVA). Responsiveness to bitter and
      astringent stimuli was associated in a non-linear fashion with intake of all
      alcoholic beverage types, with the highest consumption observed in middle
      quantiles. Sourness responsiveness tended to be inversely associated with all
      measures of alcohol consumption. Regardless of sensation, the most responsive
      quantiles tended to drink less, although sweetness showed little relationship
      between responsiveness and intake. For wine, increased umami and metallic
      responsiveness tended to predict lower total consumption and frequency. A limited
      examination of individuals who abstain from all alcohol indicated a tendency
      toward higher responsiveness than alcohol consumers to sweetness, sourness,
      bitterness, and saltiness (biserial correlation), suggesting that broadly-tuned
      orosensory responsiveness may be protective against alcohol use and possibly
      misuse. Overall, these findings confirm the importance of orosensory
      responsiveness in mediating consumption of alcohol, and indicate areas for
      further research.

PMID- 28433463
TI  - Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and
      function.
AB  - Actin is a profoundly influential protein; it impacts, among other processes,
      membrane morphology, cellular motility, and vesicle transport. Actin can
      polymerize into long filaments that push on membranes and provide support for
      intracellular transport. Actin filaments have polar ends: the fast-growing
      (barbed) end and the slow-growing (pointed) end. Depolymerization from the
      pointed end supplies monomers for further polymerization at the barbed end.
      Tropomodulins (Tmods) cap pointed ends by binding onto actin and tropomyosins
      (Tpms). Tmods and Tpms have been shown to regulate many cellular processes;
      however, very few studies have investigated their joint role in the nervous
      system. Recent data directly indicate that they can modulate neuronal morphology.
      Additional studies suggest that Tmod and Tpm impact molecular processes
      influential in synaptic signaling. To facilitate future research regarding their
      joint role in actin regulation in the nervous system, we will comprehensively
      discuss Tpm and Tmod and their known functions within molecular systems that
      influence neuronal development.

PMID- 28433465
TI  - Dumping symptoms is triggered by fat as well as carbohydrates in patients
      operated with Roux-en-Y gastric bypass.
AB  - BACKGROUND: Dumping syndrome after Roux-en-Y gastric bypass (RYGB) is
      traditionally associated with the consumption of refined carbohydrates, but the
      role of dietary fat is unclear. OBJECTIVES: This study compares symptoms after
      consumption of a carbohydrate-rich or fat-rich beverage to determine perceived
      symptoms, glycemic control, and pulse rate. SETTING: University hospital.
      METHODS: We assessed perceived symptoms (Sigstad's Dumping Index) and glycemic
      control (P-glucose and S-insulin) as well as autonomic nervous system activity
      (reflected by arterial pulse rate) after a standardized liquid meal test (440
      kcal/300 mL carbohydrates [CARB] or fat [FAT]) in a randomized crossover blinded
      setting. Blood samples were drawn before and 1, 15, 30, and 60 minutes after
      finishing each meal and the area under the curve (AUC) was calculated. RESULTS:
      Twelve patients 42+/-10 months after undergoing RYGB were studied. AUC differed
      between drinks for glucose (P = .003) and insulin (P = .005). Pulse rate
      increased more after CARB than after FAT (P = .01). AUC for perceived symptoms in
      the Sigstad's Dumping Index were similar after meals (P = .79), yet the pattern
      of type of symptoms differed. CONCLUSION: In patients with RYGB, a meal with
      predominant fat content resulted in as much perceived dumping symptoms as a
      carbohydrate-profiled meal. As expected, an increase in glucose and insulin
      levels were found only after carbohydrate intake and the pulse rise was more
      pronounced for carbohydrates than fat. Dietary counseling in patients undergoing
      RYGB should address dietary fat as well as traditional information about
      carbohydrates to avoid dumping symptoms.

PMID- 28433467
TI  - Modeling hypohedonia following repeated social defeat: Individual vulnerability
      and dopaminergic involvement.
AB  - Social defeat in rodents putatively can model hypohedonia. The present studies
      examined models for assessing hypohedonia-like behavior and tested the hypotheses
      that 1) individual differences in baseline reward sensitivity predict
      vulnerability, and 2) defeat elicits changes in pharmacological measures of
      striatal dopaminergic function. Male Wistar rats (n=142) received repeated defeat
      (3 "triad" blocks of 3 defeats) or control handling. To determine whether defeat
      influenced consumption of SuperSac (glucose-saccharin) over an isocaloric, less
      preferred, glucose solution, a 2-choice paradigm was used. To determine repeated
      defeat effects on the reinforcing efficacy of SuperSac, a progressive-ratio
      schedule of reinforcement was used. Amphetamine-induced locomotor activity
      (0.08mg/kg, s.c.) was determined as a measure sensitive to striatal dopaminergic
      function. Defeat reduced SuperSac consumption during the first two triads-an
      effect seen in the third triad only in defeated rats with High vs. Low baseline
      SuperSac intake. The characteristic escalation in PR breakpoint for SuperSac
      normally seen in controls was absent in defeated rats, leading to a significant
      difference by the third triad. Defeat-induced blunting of the escalation in PR
      performance was greater in rats with High antecedent PR breakpoints and persisted
      2.5weeks post-defeat. Repeated defeat also blunted amphetamine-induced locomotion
      13days post-defeat. Thus, hypohedonic-like effects of social defeat were detected
      and accompanied by persistently attenuated striatal dopamine function. Early
      effects were seen for consumption of differentially-palatable solutions, and
      persistent effects were seen for the "breakpoint" motivational measure. The
      results implicate initial reward sensitivity as a risk factor for stress-induced
      hypohedonia.

PMID- 28433468
TI  - Environmental structure and energetic consequences in groups of young mice.
AB  - Microenvironments can have considerable physiological consequences for the
      inhabitants by influencing the movements of individual members. The
      microenvironment can permit more diverse aggregation patterns or restrict
      movements to certain dimensions. Here, we tested whether aspects of the
      microenvironment that influenced aggregation patterns also influenced the
      energetics of groups of young animals. We tested the effects of enclosure
      configuration on the group temperature and respiration of infant mice (Mus
      musculus). We monitored the huddle temperature and respiration of groups in flat,
      concave and conical enclosures, which varied in shape and available space, and
      consequently the types of movements they permitted. We found that the amount of
      available space (or density) had a stronger effect on the group temperature than
      did the shape of the enclosure or types of permissible movements. We found no
      evidence that density or shape of the arena strongly affected the respiration
      rate of the group, with groups showing similar levels of oxygen consumption in
      all treatments. The lower density enclosures conveyed a considerable metabolic
      savings to groups in comparison to those tested in a higher density enclosure.
      These findings show density can have a large effect on the energetics of young
      mice, and provide insights on how simple features of the environment will
      influence physiology in a changing world.

PMID- 28433469
TI  - Delayed effect of early-life corticosterone treatment on adult anti-predator
      behavior in a common passerine.
AB  - Acute, short-term effects of early-life stress and associated glucocorticoid
      upregulation on behavior are widely documented across vertebrates. However, the
      persistence and severity of these effects are largely unknown, especially through
      the adult stage and in wild species. Here, we investigate long-term effects of
      experimental post-natal increases in a circulating glucocorticoid on antipredator
      behavior in wild house sparrows (Passer domesticus) tested in captivity. We
      manipulate circulating corticosterone concentration in wild, free-living
      nestlings, transfer fledglings to captivity, and test juveniles and adults for
      two measures of antipredator behavior: evasiveness during a direct human
      encounter, and propensity to escape from a risky environment. We find no effect
      of early-life stress hormone manipulation on escape behavior, but a delayed
      effect on evasive behavior: evasive behavior was depressed in adults but not
      juveniles, and influenced by current body condition. These results highlight the
      importance of state-behavior interactions and life stage in assessing long-term
      effects of early-life stress, and provide rare evidence for delayed effects of
      early-life stress to adults of a wild avian species.

PMID- 28433470
TI  - Daily supplementation of dietary protein improves the metabolic effects of GLP-1
      based pharmacotherapy in lean and obese rats.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from intestinal L
      cells in response to food entering into the gastrointestinal tract. GLP-1-based
      pharmaceuticals improve blood glucose regulation and reduce feeding. Specific
      macronutrients, when ingested, may trigger GLP-1 secretion and enhance the
      effects of systemic sitagliptin, a pharmacological inhibitor of DPP-IV (an enzyme
      that rapidly degrades GLP-1). In particular, macronutrient constituents found in
      dairy foods may act as potent secretagogues for GLP-1, and acute preclinical
      trials show that ingestion of dairy protein may represent a promising adjunct
      behavioral therapy in combination with sitagliptin. To test this hypothesis
      further, chow-maintained or high-fat diet (HFD)-induced obese rats received daily
      IP injections of sitagliptin (6mg/kg) or saline in combination with a twice-daily
      8ml oral gavage of milk protein concentrate (MPC; 80/20% casein/whey;
      0.5kcal/ml), soy protein (non-dairy control; 0.5kcal/ml) or 0.9% NaCl for two
      months. Food intake and body weight were recorded every 24-48h; blood glucose
      regulation was examined at baseline and at 3 and 6.5weeks via a 2h oral glucose
      tolerance test (OGTT; 25% glucose; 2g/kg). MPC and soy protein significantly
      suppressed cumulative caloric intake in HFD but not chow-maintained rats. AUC
      analyses for OGTT show suppression in glycemia by sitagliptin with MPC or soy in
      chow- and HFD-maintained rats, suggesting that chronic ingestion of dairy or soy
      proteins may augment endogenous GLP-1 signaling and the glycemic- and food intake
      suppressive effects of DPP-IV inhibition.

PMID- 28433471
TI  - Is transurethral resection alone enough for the diagnosis of histological
      variants? A single-center study.
AB  - INTRODUCTION: To evaluate incidence of histological variants and grade agreement
      between transurethral resection (TUR) and radical cystectomy (RC) in patients
      with bladder cancer. METHODS: A total of 779 patients treated with TUR and
      subsequently with RC between 1990 and 2013 at a single center were analyzed
      retrospectively. Variant histology classifications used in our analyses were
      sarcomatoid, small cell, squamous, or micropapillary. Grade agreement was
      calculated using the Cohen kappa coefficient. Logistic regression analyses were
      built to predict adverse pathologic features from histological variants at TUR.
      RESULTS: Considering TUR, 213 (27.3%) patients were diagnosed with histological
      variants. Of these, 2.1% (n = 16) were found with sarcomatoid variant, 1.7% (n =
      13) with small cell, 7.1% (n = 55) with squamous, 12.5% (n = 97) with
      micropapillary. Considering RC, 212 (27.2%) patients were diagnosed with
      histological variants. Poor agreement was found considering micropapillary
      variant and the presence of a histological variant in general (0.11 and 0.27,
      respectively). Intermediate agreement was found analyzing the presence of
      sarcomatoid, small cell, and squamous variants (0.43, 0.61, and 0.61,
      respectively). Small cell carcinoma at TUR was found associated with an increased
      risk of harboring positive soft tissue surgical margin (odds ratio = 2.08; CI:
      1.27-3.41; P = 0.03). CONCLUSIONS: One out of our patients with bladder cancer
      was diagnosed with a histological variant either at TUR and RC. We found poor
      agreement between TUR and RC. Our findings highlight that TUR alone is not
      sufficient to accurately evaluate the presence of histological variants that may
      have an effect on treatment and survival outcomes.

PMID- 28433472
TI  - The influence of platelet rich plasma on synovial fluid volumes, protein
      concentrations, and severity of pain in patients with knee osteoarthritis.
AB  - Knee pain is commonly seen in orthopedic and rehabilitation outpatient clinical
      settings. Patients with knee osteoarthritis (OA) are often complicated with joint
      soreness, swelling, weakness, and pain. These complaints are often caused by the
      excessive amount of synovial fluid (SF) accumulated in the bursae around the knee
      joint. This study was aimed to evaluate the effectiveness of platelet rich plasma
      (PRP) in treating patients with minor to moderate knee osteoarthritis (OA)
      combined with supra-patellar bursitis using a proteomic approach and clinical
      evaluation tool. In this study, 24 elderly patients with minor to moderate knee
      OA combined with supra-patellar bursitis were recruited. Musculoskeletal
      ultrasound was used for accurate needle placement for the aspiration of SF
      followed by subsequent PRP injections. Three monthly PRP injections were
      performed to the affected knees for a total of 3months. Approximately after the
      2nd PRP injection, significant decreases in SF total protein concentrations,
      volumes, and Lequesne index values were observed. SF proteins associated with
      chelation and anti-aging physiological functions such as matrilin, transthyretin,
      and complement 5 increased at least 2-fold in concentrations. Proteins associated
      with inflammation, such as apolipoprotein A-I, haptoglobin, immunoglobulin kappa
      chain, transferrin, and matrix metalloproteinase decreased at least 2-fold in
      concentrations. Therefore, at least two monthly PRP injections may be beneficial
      for treating patients with minor to moderate knee OA combined with supra-patellar
      bursitis.

PMID- 28433473
TI  - Sex difference in the heat shock response to high external load resistance
      training in older humans.
AB  - BACKGROUND: Literature reports on the effects of resistance training on heat
      shock protein70 (Hsp70) adaptation in older subjects are scarce. Moreover, the
      optimum training load required to obtain a beneficial adaptation profile is
      lacking. Therefore, the aim of this study was to determine the effects of
      resistance training at various external loads on extracellular Hsp70 (eHsp70)
      resting levels in older humans. METHODS: Fifty-six community-dwelling older (68+/
      5years) volunteers were randomized to 12weeks of resistance training (3*/week) at
      either high-resistance (HIGH, 8 males, 10 females, 2*10-15 repetitions at 80%
      1RM), low resistance (LOW, 9 Males, 10 Females, 1*80-100 repetitions at 20% 1RM),
      or mixed low resistance (LOW+, 9 Males, 10 Females, 1*60 repetitions at 20% 1RM
      followed by 1*10-20 repetitions at 40% 1RM). Serum was available from 48 out of
      the 56 participants at baseline and after 12weeks for determination of eHsp70.
      Mid-thigh muscle volume (computed tomography), muscle strength (1RM & Biodex
      dynamometer) and physical functioning (including 6min walk distance [6MWD]) were
      assessed. RESULTS: There was a sex-related dichotomy in the heat shock response
      to high external load training. We observed a significant decrease in eHsp70
      concentration in the HIGH group for female, but not male, subjects. At baseline,
      men had a larger muscle volume, leg press and leg extension 1RM compared to women
      (all p<0.001). Also, the 6MWD was significantly higher in men compared to women
      at baseline. However, this difference disappeared when correcting for height.
      Moreover, the overall functional performance and physical activity scores were
      similar in men and women. None of the participants' characteristics nor any of
      the outcome variables differed between groups at baseline. There was a
      significant increase in the strength and physical performance parameters in both
      men and women post-exercise (all p<0.05). Females in the HIGH group clearly
      demonstrated a larger gain in leg press 1RM and the isometric knee extensor
      strength compared to females in the LOW group (p=0.036 and p=0.044,
      respectively). More so, we found an inverse association between the change in
      eHsp70 levels and improvement in isometric knee extensor strength and 6MWD (r=
      0.443, p=0.002 and r=-0.428, p=0.002; respectively) post exercise. CONCLUSIONS:
      Our results show that resistance training at high external load decreases the
      resting levels of eHsp70 in older females. Whether this reflects a better health
      status requires further investigation.

PMID- 28433474
TI  - Beneficial effect of tocilizumab in myasthenia gravis refractory to rituximab.
AB  - Muscle fatigue associated with myasthenia gravis is caused by autoantibodies
      interfering with neuromuscular transmission. Immunomodulating treatment is widely
      used in moderate to severe myasthenia, although the use of newer biological drugs
      except rituximab is rare. We describe the effect of tocilizumab, a blocker of
      interleukin-6 signalling, in two female myasthenia patients with high titres of
      serum acetylcholine receptor antibodies and insufficient response to rituximab.
      The first patient had been treated with high dose immunoglobulins regularly for
      several years and the second patient had been treated both with different oral
      immune suppressants and immunoglobulins before testing a low dose of rituximab
      without significant clinical effect. Subsequent treatment with tocilizumab
      resulted in clinical improvement within a few months. The first patient was
      switched back to rituximab, which resulted in worsening until tocilizumab was
      restarted. Tocilizumab can be a therapeutic option in cases not responding to
      rituximab.

PMID- 28433475
TI  - Targeted population screening of late onset Pompe disease in unspecified myopathy
      patients for Korean population.
AB  - We performed targeted population screening of late onset Pompe disease (LOPD) in
      unspecified myopathy patients, because early diagnosis is difficult due to its
      heterogeneous clinical features. We prospectively enrolled 90 unrelated myopathic
      patients who had one or more signs out of five LOPD-like clinical findings
      (proximal weakness, axial weakness, lingual weakness, respiratory difficulty,
      idiopathic hyperCKemia). Acid alpha glucosidase activity was evaluated with dried
      blood spot and mixed leukocyte simultaneously. For a final diagnosis of LOPD, 16
      patients with decreased enzyme activity were genotyped by GAA molecular analysis.
      We found two patients with LOPD (2.2%), and the remaining 14 patients had at
      least one G576S or E689K mutation, known as the pseudodeficiency allele. Acid
      alpha glucosidase activity of LOPD patients was significantly lower than that of
      patients with at least one pseudodeficiency allele (p = 0.017). This study is the
      first LOPD screening study for targeted Korean population, and more generally, an
      Asian population. Our findings suggest that for diagnosis of LOPD in Asian
      population, modified cutoff value of acid alpha glucosidase activity with dry
      blood spot considering that of patients having heterozygote pathogenic variants
      or pseudodeficiency alleles may reduce time and cost requirements and increase
      the comfort of patients.

PMID- 28433476
TI  - Patient with multiple acyl-CoA dehydrogenation deficiency disease and FLAD1
      mutations benefits from riboflavin therapy.
AB  - Multiple acyl-CoA dehydrogenation deficiency is genetically heterogenous
      metabolic disease with mutations in genes involved in electron transfer to the
      mitochondrial respiratory chain. Disease symptoms vary from severe neonatal form
      to late-onset presentation with metabolic acidosis, lethargy, vomiting, muscle
      pain and weakness. Riboflavin therapy has been shown to ameliorate diseases
      symptoms in some of these patients. Recently, mutations in FAD synthase have been
      described to cause multiple acyl-CoA dehydrogenation deficiency. We describe here
      the effect of riboflavin supplementation therapy in a previously reported adult
      patient with multiple acyl-CoA dehydrogenation deficiency having compound
      heterozygous gene variations in FLAD1 (MIM: 610595) encoding FAD synthase. We
      present thorough clinical history including laboratory investigations, muscle
      MRI, muscle biopsy and spiroergometric analyses comprising of a follow-up of 20
      years. Our data suggest that patients with adult-onset multiple acyl-CoA
      dehydrogenation deficiency with FLAD1 gene mutations also benefit from long-term
      riboflavin therapy.

PMID- 28433477
TI  - Novel mutations in the C-terminal region of GMPPB causing limb-girdle muscular
      dystrophy overlapping with congenital myasthenic syndrome.
AB  - Mutations in the GMPPB gene may underlie both limb girdle muscular dystrophy
      (LGMD) and congenital myasthenic syndrome (CMS). Forty-one cases have been
      reported to date and hotspot mutations are emerging in the Caucasian population.
      Clinical and pathological features of 5 patients with compound heterozygous GMPPB
      mutations were collected and retrospectively reviewed. In vitro functional
      analysis was performed to investigate the pathogeneity of GMPPB variants. The
      patients presented with proximal limb weakness in their first to second decades.
      Fluctuating muscle weakness, myalgia and calf hypertrophy were the major
      complaints. Myogenic changes on electromyography and marked attenuation on 3 Hz
      repetitive nerve stimulation were observed in all patients. Four reported a
      beneficial response to pyridostigmine. Muscle MRI showed selective involvement in
      the calf in case 1. Immunolabeling of alpha-dystroglycan was abnormal for case 1
      and case 2. Four novel missense mutations in the C-terminal region of GMPPB were
      identified, with p.(Arg357His) being present in all the cases. In vitro
      functional assays demonstrated that these variants did not markedly reduce the
      amount of GMPPB, but gave rise to an increased propensity for protein
      aggregation. Increasingly, patients with GMPPB mutations are found to present
      with an overlapping LGMD/myasthenic syndrome. The mutation spectrum in Chinese
      patients may differ from that of European populations, with the mutation
      p.(Arg357His) most frequently found. These mutations may lead to abnormal folding
      of GMPPB leading to protein aggregates in the cytoplasm rather than an overall
      loss in protein expression.

PMID- 28433478
TI  - Investigation on acute effects of enzyme replacement therapy and influence of
      clinical severity on physiological variables related to exercise tolerance in
      patients with late onset Pompe disease.
AB  - Exercise intolerance is one of the clinical hallmarks of late-onset Pompe disease
      (LOPD). We studied the acute effects of ERT on the physiological variables
      associated with exercise tolerance in patients chronically ERT treated. Moreover,
      we assessed the influence of clinical severity on the investigated variables. The
      day before (B) and the day after (A) ERT injection, 11 LOPD patients performed on
      a cycle-ergometer an exercise tolerance test to voluntary exhaustion; VO2, HR,
      RPE, and GAA activity were determined in B and A. The disease severity was
      characterized by Walton scale, 6MWT, and pulmonary function tests. No significant
      differences in the variables related to exercise tolerance were found in A vs B,
      despite a significant increase in GAA activity in peripheral lymphocytes. No
      differences in VO2 peak were observed between patients with only skeletal muscle
      impairment and patients with both skeletal and respiratory muscle impairment.
      Distance walked at 6MWT was significantly higher than VO2 peak expressed as
      percentage of normal values. In conclusion, in LOPD patients the exercise
      tolerance test is not acutely affected by ERT administration; the peripheral
      muscle component seems more prominent in determining the VO2 peak decrease than
      the respiratory component; VO2 peak might be more sensitive than 6MWT in
      estimating exercise tolerance in LOPD.

PMID- 28433479
TI  - Modeling short-range substitution order and disorder in crystals: Application to
      the Ga/Si distribution in a natrolite zeolite.
AB  - Atomic substitutions are a central feature of the physicochemical properties of
      an increasing number of solid-state materials. The complexity that this chemical
      disorder locally generates in otherwise crystalline solids poses a major
      challenge to the understanding of the relationships between the structure and
      properties of materials at the atomic and molecular level. Strategies designed to
      efficiently explore the ensemble of local chemical environments present in
      disordered crystals and predict their signatures in local spectroscopies such as
      solid-state nuclear magnetic resonance (NMR) are therefore essential. Focusing on
      the Ga/Si disorder in the framework of rubidium-exchanged gallosilicate natrolite
      zeolite (Rb-PST-1) with a high Ga content (SiGa=1.28), we show how the structure
      generation approach implemented in the new program supercell (Okhotnikov et al.
      [26]) provides an excellent basis for the understanding of complex experimental
      spectroscopic data. Furthermore, we describe how exhaustive explorations of
      atomic configurations can be performed to seek local structural ordering and/or
      disordering factors. In the case of Rb-PST-1, we more specifically explore the
      possibility to form and to detect the presence of thermodynamically unfavorable
      Ga-O-Ga connectivities. While particularly adapted to the description of dense
      materials, we demonstrate that this approach may successfully be used to
      reproduce and interpret the distributions of local structural distortions (i.e.,
      the geometrical disorder) resulting from the chemical disorder in systems as
      complex as microporous zeolites.

PMID- 28433480
TI  - The case of homeopathy, "how to search PubMed" may be a first step.

PMID- 28433481
TI  - Genetics of common complex diseases: a view from Iceland.
AB  - In the past decade, large scale genotyping has led to discoveries of numerous
      sequence variants that confer increased risk of many common complex diseases.
      Interestingly, a substantial proportion of pioneering genetic work has originated
      from the small nation of Iceland and has been facilitated by an extensive
      genealogy database. We provide examples of relevant observations made so far in
      several major disease categories central to internal medicine practice. Some of
      these findings offer new mechanistic clues into the pathophysiology of common
      disorders and may suggest novel approaches in diagnosis and drug therapy.
      However, a number of unresolved issues remain that will be subject of future
      research, driven by recent advances in high-throughput sequencing of the genome.
      At the same time, we are ready to begin transforming the abundant existing
      genetic data into practical clinical knowledge with the aim of improving the
      delivery of medical care. The era of precision medicine has arrived.

PMID- 28433482
TI  - Variations of target volume definition and daily target volume localization in
      stereotactic body radiotherapy for early-stage non-small cell lung cancer
      patients under abdominal compression.
AB  - We aimed to compare gross tumor volumes (GTV) in 3-dimensional computed
      tomography (3DCT) simulation and daily cone beam CT (CBCT) with the internal
      target volume (ITV) in 4-dimensional CT (4DCT) simulation in stereotactic body
      radiotherapy (SBRT) treatment of patients with early-stage non-small cell lung
      cancer (NSCLC) under abdominal compression. We retrospectively selected 10
      patients with NSCLC who received image-guided SBRT treatments under abdominal
      compression with daily CBCT imaging. GTVs were contoured as visible gross tumor
      on the planning 3DCT and daily CBCT, and ITVs were contoured using maximum
      intensity projection (MIP) images of the planning 4DCT. Daily CBCTs were
      registered with 3DCT and MIP images by matching of bony landmarks in the thoracic
      region to evaluate interfractional GTV position variations. Relative to MIP-based
      ITVs, the average 3DCT-based GTV volume was 66.3 +/- 17.1% (range: 37.5% to
      92.0%) (p < 0.01 in paired t-test), and the average CBCT-based GTV volume was
      90.0 +/- 6.7% (daily range: 75.7% to 107.1%) (p = 0.02). Based on bony anatomy
      matching, the center-of-mass coordinates for CBCT-based GTVs had maximum absolute
      shift of 2.4 mm (left-right), 7.0 mm (anterior-posterior [AP]), and 5.2 mm
      (superior-inferior [SI]) relative to the MIP-based ITV. CBCT-based GTVs had
      average overlapping ratio of 81.3 +/- 11.2% (range: 45.1% to 98.9%) with the MIP
      based ITV, and 57.7 +/- 13.7% (range: 35.1% to 83.2%) with the 3DCT-based GTV.
      Even with abdominal compression, both 3DCT simulations and daily CBCT scans
      significantly underestimated the full range of tumor motion. In daily image
      guided patient setup corrections, automatic bony anatomy-based image registration
      could lead to target misalignment. Soft tissue-based image registration should be
      performed for accurate treatment delivery.

PMID- 28433484
TI  - Corrigendum to "Biological characterization of PM226, a chromenoisoxazole, as a
      selective CB2 receptor agonist with neuroprotective profile" [Pharmacol. Res. 110
      (August 2016) (2016) 205-215].

PMID- 28433483
TI  - Functional image-guided stereotactic body radiation therapy planning for patients
      with hepatocellular carcinoma.
AB  - The aim of the current planning study is to evaluate the ability of gadoxetate
      disodium-enhanced magnetic resonance imaging (EOB-MRI)-guided stereotactic body
      radiation therapy (SBRT) planning by using intensity-modulated radiation therapy
      (IMRT) techniques in sparing the functional liver tissues during SBRT for
      hepatocellular carcinoma. In this study, 20 patients with hepatocellular
      carcinoma were enrolled. Functional liver tissues were defined according to
      quantitative liver-spleen contrast ratios >= 1.5 on a hepatobiliary phase scan.
      Functional images were fused with the planning computed tomography (CT) images;
      the following 2 SBRT plans were designed using a "step-and-shoot" static IMRT
      technique for each patient: (1) an anatomical SBRT plan optimization based on the
      total liver; and (2) a functional SBRT plan based on the functional liver. The
      total prescribed dose was 48 gray (Gy) in 4 fractions. Dosimetric parameters,
      including dose to 95% of the planning target volume (PTV D95%), percentages of
      total and functional liver volumes, which received doses from 5 to 30 Gy (V5 to
      V30 and fV5 to fV30), and mean doses to total and functional liver (MLD and fMLD,
      respectively) of the 2 plans were compared. Compared with anatomical plans,
      functional image-guided SBRT plans reduced MLD (mean: plan A, 5.5 Gy; and plan F,
      5.1 Gy; p < 0.0001) and fMLD (mean: plan A, 5.4 Gy; and plan F, 4.9 Gy; p <
      0.0001), as well as V5 to V30 and fV5 to fV30. No differences were noted in PTV
      coverage and nonhepatic organs at risk (OARs) doses. In conclusion, EOB-MRI
      guided SBRT planning using the IMRT technique may preserve functional liver
      tissues in patients with hepatocellular carcinoma (HCC).

PMID- 28433485
TI  - Hospital mortality in cirrhotic patients at a tertiary care center.
AB  - INTRODUCTION: Cirrhosis of the liver is known for its high risk of mortality
      associated with episodes of acute decompensation. There is an even greater risk
      in patients that present with acute-on-chronic liver failure. The identification
      of patients at higher risk for adverse outcomes can aid in making the clinical
      decisions that will improve the prognosis for these patients. AIMS: To determine
      in-hospital mortality and evaluate the epidemiologic and clinical characteristics
      of patients with cirrhosis of the liver seen at a tertiary referral hospital.
      METHODOLOGY: A descriptive, observational, cohort study was conducted on adult
      patients with cirrhosis of the liver, admitted to a tertiary care center in
      Bucaramanga, Colombia, within the time frame of March 1, 2015 and February 29,
      2016. RESULTS: Eighty-one patients with a mean age of 62 years were included in
      the study. The main etiology of the cirrhosis was alcoholic (59.3%). In-hospital
      mortality was 23.5% and the most frequent cause of death was septic shock
      (68.4%), followed by hypovolemic shock (10.5%). A MELD score>=18, a leukocyte
      count>12,000/ul, and albumin levels below<2.5g/dl were independent factors
      related to hospital mortality. CONCLUSIONS: In-hospital mortality in cirrhotic
      patients is high. Sepsis and bleeding are the 2 events leading to acute-on
      chronic liver failure and death. A high MELD score, elevated leukocyte count, and
      low level of albumin are related to poor outcome during hospitalization. Adjusted
      prevention-centered public health measures and early and opportune diagnosis of
      this disease are needed to prevent the development of complications and to
      improve outcome in cirrhotic patients.

PMID- 28433486
TI  - Gallstone ileus: An overview of the literature.
AB  - INTRODUCTION: Gallstone ileus represents 4% of the causes of bowel obstruction in
      the general population, but increases to 25% in patients above the age of 65
      years. Gallstone ileus does not present with unique symptoms, making diagnosis
      difficult. Its management is surgical, but there is no consensus as to which of
      the different surgical techniques is the procedure of choice. At present, there
      is no recent review of this pathology. AIM: To conduct an up-to-date review of
      this disease. MATERIALS AND METHODS: Articles published within the time frame of
      2000 to 2014 were found utilizing the PUBMED, EMBASE, and Cochrane Library search
      engines with the terms "gallstone ileus" plus "review" and the following filters:
      "review", "full text", and "humans". RESULTS: The results of this review showed
      that gallstone ileus etiology was due to intestinal obstruction from a gallstone
      that migrated into the intestinal lumen through a bilioenteric fistula. The
      presence of 2 of the 3 Rigler's triad signs was considered diagnostic. Abdominal
      tomography was the imaging study of choice for gallstone ileus diagnosis and the
      surgical procedures for management were enterolithotomy, one-stage surgery, and
      two-stage surgery. Enterolithotomy had lower morbidity and mortality than the
      other 2 procedures. CONCLUSIONS: The aim of gallstone ileus treatment is to
      release the obstruction, which is done through enterolithotomy. It is the
      recommended technique for gallstone ileus management because of its lower
      morbidity and mortality, compared with the other techniques.

PMID- 28433488
TI  - Guided Internet-based Psycho-educational Intervention Using Cognitive Behavioral
      Therapy and Self-management for Individuals with Chronic Pain: A Feasibility
      Study.
AB  - When considering barriers to chronic pain treatment, there is a need to deliver
      nonpharmacological therapies in a way that is accessible to all individuals who
      may benefit. To conduct feasibility testing using a guided, Internet-based
      intervention for individuals with chronic pain, a novel, Internet-based, chronic
      pain intervention (ICPI) was developed, using concepts proven effective in face
      to-face interventions. This study was designed to assess usability of the ICPI
      and feasibility of conducting larger-scale research, and to collect preliminary
      data on effectiveness of the intervention. Data were collected at baseline, after
      each of the six intervention modules, and 12 weeks after intervention completion.
      Forty-one participants completed baseline questionnaires, and 15 completed the 12
      week postintervention questionnaires. At baseline, all participants reported
      satisfaction with the structure of the intervention and ease of use. Internet
      based platforms such as Facebook aided in accrual of participants, making further
      large-scale study of the ICPI feasible. There is preliminary evidence suggesting
      that the ICPI improves emotional function but not physical function, with a small
      but significant decrease in pain intensity and pain interference. Most
      participants felt they benefited at least minimally as a result of using the
      ICPI. The ICPI was well received by participants and demonstrated positive
      outcomes in this preliminary study. Further research with more participants is
      feasible and necessary to fully assess the effect of this intervention.

PMID- 28433487
TI  - rAMPing Up Stress Signaling: Protein AMPylation in Metazoans.
AB  - Protein AMPylation - the covalent attachment of an AMP residue to amino acid side
      chains using ATP as the donor - is a post-translational modification (PTM)
      increasingly appreciated as relevant for both normal and pathological cell
      signaling. In metazoans single copies of filamentation induced by cAMP (fic)
      domain-containing AMPylases - the enzymes responsible for AMPylation -
      preferentially modify a set of dedicated targets and contribute to the perception
      of cellular stress and its regulation. Pathogenic bacteria can exploit AMPylation
      of eukaryotic target proteins to rewire host cell signaling machinery in support
      of their propagation and survival. We review endogenous as well as parasitic
      protein AMPylation in metazoans and summarize current views of how fic-domain
      containing AMPylases contribute to cellular proteostasis.

PMID- 28433489
TI  - Analysis of the oligosaccharides in Japanese rice wine, sake, by hydrophilic
      interaction liquid chromatography-time-of-flight/mass spectrometry.
AB  - A traditional Japanese alcoholic beverage, sake, contains several
      oligosaccharides, which are associated with the taste of sake; however, little is
      known about the specific molecular species and concentrations of oligosaccharides
      in sake. Here, we developed an analytical method using hydrophilic interaction
      liquid chromatography-time-of-flight/mass spectrometry (HILIC-TOF/MS) which
      successfully detects the oligosaccharides in sake. A series of oligosaccharides
      with successive degree of polymerization (DP) values up to 18 were identified in
      sake for the first time, which we have named sake oligosaccharides (SAOs). The
      concentrations of the SAOs with DP = 3-8 were estimated to be in the range of 200
      2000 ppm. Quantitative analysis of 6 different sake samples for SAOs with DP=2-8
      and the other saccharides showed that the amount of each SAO differs
      significantly among the sake samples. Enzymatic digestion analysis suggested that
      the SAOs are probably branched maltooligosaccharides in structure, which are
      resistant to beta-amylase.

PMID- 28433490
TI  - Evaluating Health of Emerging Economies Through the Eyes of Heart Valve Disease
      in the Transcatheter Era.
AB  - China and India are the 2 fastest growing major world economies. However, they
      suffer from great differences in health policies, demographics, and rates of
      population growth. Whereas China has seen a steep decline in rheumatic heart
      disease (RHD) and a rise in life expectancy, India continues to suffer from a
      significant burden of RHD due to insufficient distribution of economic prosperity
      to health care, denser population, and ineffective application of World Health
      Organization RHD prevention guidelines. As China faces the burden of the world's
      largest geriatric population, focus has shifted to calcific aortic stenosis for
      which it prepares by expansions in the field of transcatheter aortic valve
      replacement. Conversely, India has a younger population and a lower average life
      expectancy. Therefore, focus in India has still not shifted to calcific aortic
      stenosis as a major cause of morbidity and mortality as RHD continues to
      constitute the bulk of valvular heart disease.

PMID- 28433491
TI  - Youth Engagement for NCD Prevention Policies: Rising NCD in India and Youth as
      Change Enablers.

PMID- 28433492
TI  - Is TAVR Ready for the Global Aging Population?
AB  - The emergence of the global pandemic of chronic diseases necessitates critical
      assessment of interventions that can be targeted at both the individual and
      population levels. Among cardiovascular diseases, the increasing prevalence of
      valvular heart diseases such as aortic stenosis parallels the rising burden of
      atherosclerotic cardiovascular diseases. As an alternative to surgical aortic
      valve replacement, technological innovation has allowed development of minimally
      invasive transcatheter aortic valve replacement (TAVR). This review examines
      whether TAVR can be applicable in low-resource regions across the world. Although
      revolutionary, TAVR is currently complex and requires a "Heart Team" approach for
      optimized patient care. We propose the emergence of telemedicine networks, newer
      valve designs that allow implementation of minimal approaches, and the use of
      minimal numbers of specialists for adapting TAVR to settings where surgical
      backup is not available. With efforts to reduce resource utilization, these
      alternate strategies have the potential to affect implementation of TAVR
      globally.

PMID- 28433493
TI  - A rare and emerging pathogen: Raoultella planticola identification based on 16S
      rRNA in an infant.
AB  - Raoultella planticola is rarely associated with clinical infection, and a limited
      number of pediatric cases have been reported. Herein we report a case of
      bacteremia presumptively secondary to bilateral conjunctivitis in an infant
      caused by R. planticola which was successfully treated with piperacillin
      tazobactam. It should be kept in mind that R. planticola can be a pathogen in
      pediatric age groups.

PMID- 28433494
TI  - Patterns of care and clinical outcomes in primary oesophageal gastrointestinal
      stromal tumours (GIST): A retrospective study of the French Sarcoma Group (FSG).
AB  - BACKGROUND: Oesophageal GIST (ESOGIST) are very rare tumours requiring special
      consideration regarding diagnosis, surgical management, and perioperative
      treatment. METHODS: A retrospective study was conducted across 9 centres in the
      French Sarcoma Group (FSG) to characterize all patients in the years 2000-2014.
      RESULTS: Seventeen patients (pts) with primary localized ESOGIST were identified,
      with median age 69 years (36-81) and 11 females. Eight tumours (T) occurred in
      the lower third of the oesophagus, five in the oesophageal gastric junction, two
      in the superior third, and two in the middle third. All pts underwent
      oesophagoscopy and/or endoscopic ultrasound (EUS) and CT scan. Fifteen had EUS
      guided biopsy. Nine pts received Imatinib (IM) as initial treatment resulting in
      six PR, three SD. Tumours were resected in nine pts (53%) (7 upfront, 2 after
      IM); via enucleation in four (44%) [median size 4 cm], oesophagectomy in five
      (56%) [median size 10 cm]. Resections were R0 in three pts (33%), R1 in six
      (66%). Eight pts (47%) had no tumour resection, and one patient was never
      treated. Six pts received adjuvant IM. With a median follow-up of 24 months (7
      101), 11 pts are alive (64.7%), five died (29.4%), one was lost to follow-up. Two
      pts of 4 pts relapsed following enucleation. CONCLUSIONS: ESOGIST can be reliably
      identified pre-operatively by EUS-guided biopsy. Surgery for ESOGIST is either
      enucleation or oesophagectomy depending on tumour size, location, and patient's
      individual surgical risk. Preoperative IM therapy could improve resectability and
      should be considered if surgery is contraindicated or would lead to negative
      impact on the functional status of the patient.

PMID- 28433495
TI  - Lymph node ratio as a prognostic factor in gastric cancer patients following D1
      resection. Comparison with the current TNM staging system.
AB  - INTRODUCTION: Nodal ratio (NR) has been demonstrated to be an independent
      prognostic factor in patients with gastric cancer. We evaluated the prognostic
      role of NR comparing it with the current TNM (2010) classification in gastric
      cancer patients treated with curative (R0) D1 resection. MATERIALS AND METHODS:
      We retrospectively reviewed 110 patients who underwent R0 resection for gastric
      cancer at University Hospital of Larissa between 2002 and 2011. All patients had
      a D1 lymphadenectomy plus the nodes along the left gastric artery. Factors
      affecting survival as well as correlations between the N status, NR status and
      resected nodes were investigated. RESULTS: In univariate analysis the N and NR
      status but not the numbers of retrieved nodes were significant prognostic
      factors. Inside N1 and N2 categories, patients with different NR groups were
      present and survival of some of these subpopulations was statistically different
      at long-rank test. There was a correlation between the nodes retrieved and N
      status but not with the NR category. In multivariate analysis both N status
      (HR=1.45; 95% C.I. = 1.19-1.89) and NR (HR=4.53; 95% C.I. = 1.86-11.03) found to
      be independent prognostic factors of survival. CONCLUSION: Prognostic
      significance of N status and NR status was comparable. Unlike N status, NR is
      independent by the number of resected nodes, and therefore it is particularly
      useful in case of conventional lymphadenectomy.

PMID- 28433496
TI  - A novel storage system for cryoEM samples.
AB  - We present here a new CryoEM grid boxes storage system designed to simplify
      sample labeling, tracking and retrieval. The system is based on the crystal pucks
      widely used by the X-ray crystallographic community for storage and shipping of
      crystals. This system is suitable for any cryoEM laboratory, but especially for
      large facilities that will need accurate tracking of large numbers of samples
      coming from different sources.

PMID- 28433498
TI  - Long-term effectiveness of aripiprazole once-monthly for schizophrenia is
      maintained in the QUALIFY extension study.
AB  - OBJECTIVE: To evaluate long-term safety and effectiveness of continued treatment
      with aripiprazole once-monthly 400mg (AOM 400) in patients with schizophrenia.
      METHODS: Patients who completed the QUALIFY study (NCT01795547) in the AOM 400
      arm were eligible for 6 additional once-monthly injections of AOM 400 during an
      open-label, 24-week extension (NCT01959035). Safety data were collected at each
      visit. Effectiveness measures included change from baseline in health-related
      qualify of life and functioning on the Heinrichs-Carpenter Quality of Life scale
      (QLS) and Clinical Global Impression - Severity (CGI-S) scale. RESULTS: Of the 88
      patients enrolled, 77 (88%) completed the extension study. Most common treatment
      emergent adverse events (incidence >=2%) were weight increased (6/88, 7%),
      toothache (3/88, 3%) and headache (3/88, 3%). Effectiveness was maintained during
      the extension study, with small but continued improvements from baseline: the
      least squares mean (LSM) change (95% CI) from baseline to week 24 was 2.32 (-1.21
      to 5.85) for the QLS total score and -0.10 (-0.26 to 0.06) for the CGI-S score.
      The aggregated LSM change (95% CI) from baseline of the lead-in study to week 24
      of the extension study was 11.54 (7.45 to 15.64) for the QLS total score and 
      0.98 (-1.18 to -0.79) for the CGI-S score. CONCLUSIONS: AOM 400 was well
      tolerated in patients continuing AOM treatment during the extension phase of the
      QUALIFY study. Robust and clinically meaningful improvements in health-related
      quality of life and functioning were maintained, further supporting the long-term
      clinical benefits of AOM 400 for the treatment of patients with schizophrenia.

PMID- 28433497
TI  - Clostridium difficile toxin glucosyltransferase domains in complex with a non
      hydrolyzable UDP-glucose analogue.
AB  - Clostridium difficile is the leading cause of hospital-acquired diarrhea and
      pseudomembranous colitis worldwide. The organism produces two homologous toxins,
      TcdA and TcdB, which enter and disrupt host cell function by glucosylating and
      thereby inactivating key signalling molecules within the host. As a toxin
      mediated disease, there has been a significant interest in identifying small
      molecule inhibitors of the toxins' glucosyltransferase activities. This study was
      initiated as part of an effort to identify the mode of inhibition for a small
      molecule inhibitor of glucosyltransferase activity called apigenin. In the course
      of trying to get co-crystals with this inhibitor, we determined five different
      structures of the TcdA and TcdB glucosyltransferase domains and made use of a non
      hydrolyzable UDP-glucose substrate. While we were able to visualize apigenin
      bound in one of our structures, the site was a crystal packing interface and not
      likely to explain the mode of inhibition. Nevertheless, the structure allowed us
      to capture an apo-state (one without the sugar nucleotide substrate) of the TcdB
      glycosyltransferase domain that had not been previously observed. Comparison of
      this structure with structures obtained in the presence of a non-hydrolyzable UDP
      glucose analogue have allowed us to document multiple conformations of a C
      terminal loop important for catalysis. We present our analysis of these five new
      structures with the hope that it will advance inhibitor design efforts for this
      important class of biological toxins.

PMID- 28433499
TI  - Changes in the expression of metabotropic glutamate receptor 5 (mGluR5) in a
      ketamine-based animal model of schizophrenia.
AB  - It has been shown that the metabotropic glutamate receptor subtype 5 (mGluR5) is
      functionally associated with the NMDA subtype of the glutamate receptor family
      (NMDA receptors). These two receptors colocalize in brain regions associated with
      schizophrenia. Although the role of the NMDA receptor in cognitive and negative
      symptoms of schizophrenia is well studied, information about the role of mGluR5
      receptors in schizophrenia is sparse. In our work, we show that subchronic
      administration of ketamine, a well-studied, non-competitive antagonist of NMDA
      receptors, caused cognitive deficits in rats as shown by testing novel object
      recognition (NOR). Moreover, we reveal that subchronic administration of ketamine
      increased the mRNA and protein expression levels of mGluR5 receptors in regions
      CA1 and CA3 of the dorsal part of the hippocampus, both of which are strongly
      associated with the formation of visual memory, which is tested via NOR. We
      postulate that increased expression of mGluR5 receptors in the dorsal part of the
      hippocampus may reflect compensatory changes to imbalanced glutamate
      neurotransmission associated with the hypoactivation of NMDA receptors.

PMID- 28433500
TI  - Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a
      large pooled cohort of stable schizophrenia patients.
AB  - The MATRICS Consensus Cognitive Battery (MCCB) was developed to assess cognitive
      treatment effects in schizophrenia clinical trials, and is considered the FDA
      gold standard outcome measure for that purpose. The aim of the present study was
      to establish pre-treatment psychometric characteristics of the MCCB in a large
      pooled sample. The dataset included 2616 stable schizophrenia patients enrolled
      in 15 different clinical trials between 2007 and 2016 within the United States
      (94%) and Canada (6%). The MCCB was administered twice prior to the initiation of
      treatment in 1908 patients. Test-retest reliability and practice effects of the
      cognitive composite score, the neurocognitive composite score, which excludes the
      domain Social Cognition, and the subtests/domains were examined using Intra-Class
      Correlations (ICC) and Cohen's d. Simulated regression models explored which
      domains explained the greatest portion of variance in composite scores. Test
      retest reliability was high (ICC=0.88) for both composite scores. Practice
      effects were small for the cognitive (d=0.15) and neurocognitive (d=0.17)
      composites. Simulated bootstrap regression analyses revealed that 3 of the 7
      domains explained 86% of the variance for both composite scores. The domains that
      entered most frequently in the top 3 positions of the regression models were
      Speed of Processing, Working Memory, and Visual Learning. Findings provide
      definitive psychometric characteristics and a benchmark comparison for clinical
      trials using the MCCB. The test-retest reliability of the MCCB composite scores
      is considered excellent and the learning effects are small, fulfilling two of the
      key criteria for outcome measures in cognition clinical trials.

PMID- 28433501
TI  - Disrupted in Schizophrenia 1 regulates the processing of reelin in the perinatal
      cortex.
AB  - Disrupted in Schizophrenia 1 (DISC1) is a prominent gene in mental illness
      research, encoding a scaffold protein known to be of importance in the developing
      cerebral cortex. Reelin is a critical extracellular protein for development and
      lamination of the prenatal cortex and which has also been independently
      implicated in mental illness. Regulation of reelin activity occurs through
      processing by the metalloproteinases ADAMTS-4 and ADAMTS-5. Through cross
      breeding of heterozygous transgenic DISC1 mice with heterozygous reeler mice,
      which have reduced reelin, pups heterozygous for both phenotypes were generated.
      From these, we determine that transgenic DISC1 leads to a reduction in the
      processing of reelin, with implications for its downstream signalling element
      Dab1. An effect of DISC1 on reelin processing was confirmed in vitro, and
      revealed that intracellular DISC1 affects ADAMTS-4 protein, which in turn is
      exported and affects processing of extracellular reelin. In transgenic rat
      cortical cultures, an effect of DISC1 on reelin processing could also be seen
      specifically in early, immature neurons, but was lost in calretinin and reelin
      positive mature neurons, suggesting cell-type specificity. DISC1 therefore acts
      upstream of reelin in the perinatal cerebral cortex in a cell type/time specific
      manner, leading to regulation of its activity through altered proteolytic
      cleavage. Thus a functional link is demonstrated between two proteins, each of
      independent importance for both cortical development and associated cognitive
      functions leading to behavioural maladaptation and mental illness.

PMID- 28433502
TI  - Una Ryan: On the Importance of Clean Potable Water.

PMID- 28433503
TI  - MR fingerprinting reconstruction with Kalman filter.
AB  - Magnetic resonance fingerprinting (MR fingerprinting or MRF) is a newly
      introduced quantitative magnetic resonance imaging technique, which enables
      simultaneous multi-parameter mapping in a single acquisition with improved time
      efficiency. The current MRF reconstruction method is based on dictionary
      matching, which may be limited by the discrete and finite nature of the
      dictionary and the computational cost associated with dictionary construction,
      storage and matching. In this paper, we describe a reconstruction method based on
      Kalman filter for MRF, which avoids the use of dictionary to obtain continuous MR
      parameter measurements. With this Kalman filter framework, the Bloch equation of
      inversion-recovery balanced steady state free-precession (IR-bSSFP) MRF sequence
      was derived to predict signal evolution, and acquired signal was entered to
      update the prediction. The algorithm can gradually estimate the accurate MR
      parameters during the recursive calculation. Single pixel and numeric brain
      phantom simulation were implemented with Kalman filter and the results were
      compared with those from dictionary matching reconstruction algorithm to
      demonstrate the feasibility and assess the performance of Kalman filter
      algorithm. The results demonstrated that Kalman filter algorithm is applicable
      for MRF reconstruction, eliminating the need for a pre-define dictionary and
      obtaining continuous MR parameter in contrast to the dictionary matching
      algorithm.

PMID- 28433504
TI  - Intensification of ultrasonic-assisted crude oil demulsification based on
      acoustic field distribution data.
AB  - Water removal is an essential step during crude oil production due to several
      problems such as increased transportation costs and high corrosion rate due to
      dissolved salts. Indirect low frequency ultrasonic energy (US), using baths, has
      been recently proposed as an effective alternative for crude oil demulsification.
      However, the reactor position during sonication and its influence on the
      demulsification efficiency for crude oil has not been evaluated. In this sense,
      the aim of this study was to develop an automated system based on an open source
      hardware for mapping the acoustic field distribution in an US bath operating at
      35kHz using a hydrophone. Data acquired with this system provided information to
      evaluate the demulsification efficiency in the different positions of the US bath
      and correlate it with the acoustic intensity distribution. The automated 3D
      mapping system revealed a higher acoustic intensity in the regions immediately
      above the transducers (ca. 0.6Wcm-2), while the other regions presented a
      relatively lower intensity (ca. 0.1Wcm-2). Experimental data demonstrated that
      reactors positioned in the most intense acoustic regions provided a much higher
      efficiency of demulsification in comparison with the ones positioned in the less
      intense acoustic field regions. Demulsification efficiency up to 93% was obtained
      with 15min of sonication (100% amplitude) using few amount of chemical
      demulsifier. Hence, this work demonstrated that the information acquired with the
      developed mapping system could be used for inducing a higher efficiency of
      demulsification only by finding the more suitable position of reactor in the US
      bath, which certainly will help development of appropriate reactors design when
      looking for such approach.

PMID- 28433505
TI  - Chemotherapy induces alternative transcription and splicing: Facts and hopes for
      cancer treatment.
AB  - Alternative promoter usage, alternative splicing and alternative
      cleavage/polyadenylation (referred here as to alternative transcription and
      splicing) are main instruments to diversify the transcriptome from a limited set
      of genes. There is a good deal of evidence that chemotherapeutic drugs affect
      these processes, but the therapeutic incidence of these effects is poorly
      documented. The scope of this study is to review the impact of chemotherapy on
      alternative transcription and splicing and to discuss potential implications in
      cancer therapy. A literature survey identified >2200 events induced by
      chemotherapeutic drugs. The molecular pathways involved in these regulations are
      briefly discussed. The GO terms associated with the alternative transcripts are
      mainly related to cell cycle/division, mRNA processing, DNA repair,
      macromolecules catabolism and chromatin. A large fraction (43%) of transcripts
      are also related to the new hallmarks of cancer, mostly genetic instability and
      replicative immortality. Finally, we ask the question of the impact of
      alternative transcription and splicing on drug efficacy and of the possible
      curative benefit of combining chemotherapy and pharmaceutical regulation of this
      process.

PMID- 28433506
TI  - Heifers express G-protein coupled receptor 61 in anterior pituitary gonadotrophs
      in stage-dependent manner.
AB  - Gonadotropin-releasing hormone receptors (GnRHRs) colocalize with insulin and
      glucocorticoid receptors in lipid rafts of the gonadotroph plasma membrane, where
      they facilitate downstream signaling. We recently found that orphan G-protein
      coupled receptor (GPR)61 is expressed in the anterior pituitary (AP) of heifers,
      leading us to speculate that GPR61 colocalizes with GnRHR in the plasma membrane
      of gonadotroph and is expressed at specific times of the reproductive cycle. To
      test this hypothesis, we examined the coexpression of GnRHR, GPR61, and either
      luteinizing hormone (LH) beta subunit or follicle-stimulating hormone (FSH) beta
      subunit in AP tissue and cultured AP cells by immunofluorescence microscopy.
      GPR61 was detected in gonadotrophs, with a majority of them being colocalized
      with GnRHR and the remainder present at other parts of the cell surface or in the
      cytoplasm. We obtained a strong positive overlap coefficient (0.71+/-0.01)
      between GPR61 and GnRHR on the cell-surface of cultured GnRHR-positive AP cells.
      Real-time PCR and western blot analyses found that expression was lower (P<0.05)
      in AP tissues during early luteal phase as compared to pre-ovulation or mid- or
      late luteal phases. Additionally, the 5?-flanking region of the GPR61 gene
      contained several sites with response elements similar to those of estrogen or
      progesterone. These data suggested that GPR61 colocalizes with GnRHR in the
      plasma membrane of gonadotrophs, and its expression changes stage-dependently in
      the bovine anterior pituitary gland.

PMID- 28433507
TI  - Use of bioreactor landfill for nitrogen removal to enhance methane production
      through ex situ simultaneous nitrification-denitrification and in situ
      denitrification.
AB  - High concentrations of nitrate-nitrogen (NO3--N) derived from ex situ
      nitrification phase can inhibit methane production during ex situ nitrification
      and in situ denitrification bioreactor landfill. A combined process comprised of
      ex situ simultaneous nitrification-denitrification (SND) in an aged refuse
      bioreactor (ARB) and in situ denitrification in a fresh refuse bioreactor (FRB)
      was conducted to reduce the negative effect of high concentrationsof NO3--N. Ex
      situ SND can be achieved because NO3--N concentration can be reduced and the
      removal rate of ammonium-nitrogen (NH4+-N) remains largely unchanged when the
      ventilation rate of ARB-A2 is controlled. The average NO3--N concentrations of
      effluent were 470mg/L in ex situ nitrification ARB-A1 and 186mg/L in ex situ SND
      ARB-A2. The average NH4+-N removal rates of ARB-A1 and ARB-A2 were 98% and 94%,
      respectively. Based on the experimental data from week 4 to week 30, it is
      predicted that NH4+-N concentration in FRB-F1 of the ex situ nitrification and in
      situ denitrification process would reach 25mg/L after 63weeks, and about 40weeks
      for the FRB-F2 of ex situ SND and in situ denitrification process . Ex situ SND
      and in situ denitrification process can improve themethane production of FRB-F2.
      The lag phase time of methane production for the FRB-F2 was 11weeks. This phase
      was significantly shorter than the 15-week phases of FRB-F1 in ex situ
      nitrification and in situ denitrification process. A seven-week
      stabilizationphase was required to increase methane content from 5% to 50% for
      FRB-F2. Methane content in FRB-F1 did not reach 50% but reached the 45% peak
      after 20weeks.

PMID- 28433508
TI  - Organs at risk in lung SBRT.
AB  - Lung stereotactic body radiotherapy (SBRT) is an accurate and precise technique
      to treat lung tumors with high 'ablative' doses. Given the encouraging data in
      terms of local control and toxicity profile, SBRT has currently become a
      treatment option for both early stage lung cancer and lung oligometastatic
      disease in patients who are medically inoperable or refuse surgical resection.
      Dose-adapted fractionation schedules and ongoing prospective trials should
      provide further evidence of SBRT safety trying to reduce toxicities and
      complications. In this heterogeneous scenario, a non-systematic review of dose
      constraints for lung SBRT was performed, including the main organs at risk in the
      thorax.

PMID- 28433509
TI  - Transcutaneous aortic valve implantation using the carotid artery access:
      Feasibility and clinical outcomes.
AB  - BACKGROUND: Transcarotid access is an alternative route for transcutaneous aortic
      valve implantation (TAVI) in patients with impossible transfemoral access. AIMS:
      We evaluated the safety, effectiveness and early and late clinical outcomes of
      CoreValve(r) implantation via the common carotid artery. METHODS: Eighteen
      patients (10 men, 8 women; mean age 84+/-5 years) at high surgical risk (mean
      EuroSCORE II 16+/-13%) with significant peripheral artery disease underwent TAVI
      via common carotid artery access under general anaesthesia. Mean aortic valve
      area was 0.64+/-0.13cm2 (0.36+/-0.07cm2/m2). RESULTS: At a mean follow-up of
      605+/-352 days, two patients (11%) had died in hospital, on days 6 and 20, as a
      result of sepsis with multiorgan failure (n=1) or pneumonia (n=1). There were no
      perioperative deaths, myocardial infarctions or strokes. Perioperative prosthesis
      embolization occurred in one patient (6%), requiring implantation of a second
      valve. In-hospital complications occurred in four patients (23%): blood
      transfusion for transient significant bleeding at the access site in one patient
      (6%); permanent pacemaker implantation in two patients (11%); and pericardial
      drainage in one patient (6%). The rate of event-free in-hospital stay was 66%.
      Post-procedural echocardiography showed very good haemodynamic performance, with
      a mean gradient of 8+/-3mmHg. Moderate paravalvular leak was present in one
      patient (6%). Mean intensive care unit stay was 48+/-31h; mean in-hospital stay
      was 7+/-3 days. CONCLUSION: TAVI performed by transcarotid access in this small
      series of severely ill patients was associated with a low incidence of
      complications, which were associated with the procedure itself rather than the
      access route.

PMID- 28433510
TI  - Biomaterial stiffness determines stem cell fate.
AB  - Stem cells have potential to develop into numerous cell types, thus they are good
      cell source for tissue engineering. As an external physical signal, material
      stiffness is capable of regulating stem cell fate. Biomaterial stiffness is an
      important parameter in tissue engineering. We summarize main measurements of
      material stiffness under different condition, then list and compare three main
      methods of controlling stiffness (material amount, crosslinking density and
      photopolymeriztion time) which interplay with one another and correlate with
      stiffness positively, and current advances in effects of biomaterial stiffness on
      stem cell fate. We discuss the unsolved problems and future directions of
      biomaterial stiffness in tissue engineering.

PMID- 28433511
TI  - Design, synthesis, and pharmacological evaluation of 4-azolyl-benzamide
      derivatives as novel GPR52 agonists.
AB  - G protein-coupled receptor 52 (GPR52) agonists are expected to improve the
      symptoms of psychiatric disorders. During exploration for a novel class of GPR52
      agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5
      (trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzamide (4u;
      half maximal effective concentration (EC50)=75nM, maximal response (Emax)=122%)
      starting from a high-throughput screening hit 3 (EC50=470nM, Emax=56%). The
      structural features of a reported GPR52 agonist were applied to 3, led to design
      4-azolylbenzamides as novel GPR52 agonists. A structure-activity relationship
      study of 4-azolylbenzamide resulted in the design of the 1,2,4-triazole
      derivative 4u, which demonstrated excellent bioavailability in rats (F=53.8%).
      Oral administration of 4u (10mg/kg) significantly suppressed methamphetamine
      induced hyperlocomotion in mice. Thus, 4u is a promising lead compound for drug
      discovery research of GPR52 agonists.

PMID- 28433512
TI  - Effect of 1,2,3-triazole salts, non-classical bioisosteres of miltefosine, on
      Leishmania amazonensis.
AB  - Here, we report the effect of new non-classical bioisosteres of miltefosine on
      Leishmania amazonensis. Fifteen compounds were synthesized and the compound
      dhmtAc, containing an acetate anion, a side chain of 10 carbon atoms linked to N
      1 and a methyl group linked to N-3, showed high and selective biological activity
      against L. amazonensis. On the intracellular amastigotes, stages of the parasite
      related to human disease, the IC50 values were near or similar to the 1.0MUM
      (0.9, 0.8 and 1.0MUM on L. amazonensis-WT, and two transgenic L. amazonensis
      expressing GFP and RFP, respectively), being more active than miltefosine.
      Furthermore, dhmtAc did not show toxic effects on human erythrocytes and
      macrophages (CC50=115.9MUM) being more destructive to the intracellular parasites
      (selectivity index>115). Promastigotes and intramacrophage amastigotes treated
      with dhmtAc showed low capacity for reversion of the effect of the compound. A
      study of the mechanism of action of this compound showed some features of
      metazoan apoptosis, including cell volume decreases, loss of mitochondrial
      membrane potential, ROS production, an increase in the intracellular lipid
      bodies, in situ labeling of DNA fragments by TUNEL labeling and
      phosphatidylserine exposure to the outerleaflet of the plasma membrane. In
      addition, the plasma membrane disruption, revealed by PI labeling, suggests cell
      death by necrosis. No increase in autophagic vacuoles formation in treated
      promastigotes was observed. Taken together, the data indicate that the
      bioisostere of miltefosine, dhmtAc, has promising antileishmanial activity that
      is mediated via apoptosis and necrosis.

PMID- 28433514
TI  - Cox-2 inhibition potentiates mouse bone marrow stem cell engraftment and
      differentiation-mediated wound repair.
AB  - BACKGROUND: Engraftment of transplanted stem cells is often limited by cytokine
      and noncytokine proinflammatory mediators at the injury site. We examined the
      role of Cyclooxygenase-2 (Cox-2)-induced cytokine-mediated inflammation on
      engraftment of transplanted bone marrow stem cells (BMSCs) at the wound site.
      METHODS: BMSCs isolated from male C57/BL6J mice were transplanted onto excisional
      splinting wounds in syngenic females in presence or absence of celecoxib, Cox-2
      specific inhibitor (50 mg/kg, body weight [b wt]), to evaluate engraftment and
      wound closure. Inflammatory cell infiltration and temporal expression of
      inflammatory cytokines at the wound bed were determined using immunohistochemical
      and quantitative-real time polymerase chain reaction (qPCR) analysis,
      respectively. Mechanistic studies were performed on a murine macrophage cell line
      (J774.2) to evaluate the effect of interleukin (IL)-17A. RESULTS: Celecoxib
      administration led to a significantly high percent of wound closure, cellular
      proliferation, collagen deposition, BMSCs engraftment and re-epithelialization at
      the wound site. Interestingly, recruitment of CD4+T cells and F4/80+ macrophages
      as well as BMSC transplantation induced up-regulation of Cox-2 and IL-17A gene
      expression levels were reverted by celecoxib administration. Exogenous
      supplementation of recombinant interleukin (rIL)-17 to J774.2 cells significantly
      increased proliferation and gene expression of cytokines -IL-1beta, IL-6, IL-8,
      IL-18 and tumor necrosis factor (TNF)-alpha via nuclear translocation of nuclear
      factor kappa B (NFkappaB)p65/50 subunit. Conditioned media of rIL-17 treated
      J774.2 cells when supplemented to BMSCs depicted a dose-dependent increase in the
      number of apoptotic cells and proapoptotic protein expression that was perturbed
      by celecoxib or IL-17 neutralizing antibody. Finally, celecoxib led to a dose
      dependent increase in BMSC differentiation into keratinocyte-like cells in vitro.
      CONCLUSION: Celecoxib protects transplanted BMSCs from Cox-2/IL-17-induced
      inflammation and increases their engraftment, differentiation into keratinocytes
      and re-epithelialization thereby potentiating wound tissue repair.

PMID- 28433513
TI  - Ortho group activation of a bromopyrrole ester in Suzuki-Miyaura cross-coupling
      reactions: Application to the synthesis of new microtubule depolymerizing agents
      with potent cytotoxic activities.
AB  - New microtubule depolymerizing agents with potent cytotoxic activities have been
      prepared with a 5-cyano or 5-oximino group attached to a pyrrole core. The
      utilization of ortho activation of a bromopyrrole ester to facilitate successful
      Suzuki-Miyaura cross-coupling reactions was a key aspect of the synthetic
      methodology. This strategy allows for control of regiochemistry with the
      attachment of four completely different groups at the 2, 3, 4 and 5 positions of
      the pyrrole scaffold. Biological evaluations and molecular modeling studies are
      reported for these examples.

PMID- 28433515
TI  - Understanding clinical development of chimeric antigen receptor T cell therapies.
AB  - BACKGROUND AIMS: In the past decade, many clinical trials with gene- and cell
      based therapies (GCTs) have been performed. Increased interest in the development
      of these drug products by various stakeholders has become apparent. Despite this
      growth in clinical studies, the number of therapies receiving marketing
      authorization approval (MAA) is lagging behind. To enhance the success rate of
      GCT development, it is essential to better understand the clinical development of
      these products. Chimeric antigen receptor (CAR) T cells are a GCT product subtype
      with promising efficacy in cancer treatment which are tested in many clinical
      trials, but have not yet received MAA. METHODS: We generated an overview of the
      characteristics of CAR T-cell clinical development in the United States, Canada
      and Europe. Subsequently, the characteristics of clinical trials with CAR T-cell
      products that proceeded to a subsequent clinical trial, used as a proxy for
      success, were compared with those that did not proceed. RESULT: From the U.S. and
      European Union clinical trial databases, 106 CAR T-cell trials were selected,
      from which 49 were linked to a subsequent trial and 57 were not. The majority of
      the trials had an academic sponsor from which most did not proceed, whereas most
      commercially sponsored trials were followed by another clinical trial.
      Furthermore, trials with a subsequent trial more frequently recruited large
      patient cohorts and were more often multicenter compared with trials that were
      not followed up. DISCUSSION: These characteristics can be used by investigators
      to better design clinical trials with CAR T cells. We encourage sponsors to plan
      clinical development ahead for a higher efficiency of product development and
      thereby achieving a higher success rate of development towards MAA.

PMID- 28433516
TI  - Intravenous mesenchymal stromal cell therapy for inflammatory bowel disease:
      Lessons from the acute graft versus host disease experience.
AB  - Bone marrow-derived mesenchymal stromal cells (BMSCs) are primitive, supportive
      cells of the bone marrow with tri-lineage potential to differentiate into bone,
      cartilage, fat and muscle. These cells possess both in vitro and in vivo
      immunomodulatory and wound-healing properties. Several studies have demonstrated
      efficacy of intravenously administered BMSCs in treating acute graft-versus-host
      disease (GvHD). Use of intravenous (IV) BMSCs in inflammatory bowel diseases
      (IBD) in humans has been limited to small studies in adults, but results have
      been promising. There remain many unanswered questions regarding safety,
      tolerability, effectiveness and optimal use of BMSCs to treat IBD, particularly
      in immunocompromised patients. This article reviews the evidence for using BMSCs
      to treat acute GvHD and how this experience may inform the potential use of BMSCs
      as a treatment for IBD.

PMID- 28433517
TI  - Causal attribution and psychobiological response to competition in young men.
AB  - A contribution to a special issue on Hormones and Human Competition.
      Psychoneuroendocrine effects of competition have been widely accepted as a clear
      example of the relationship between androgens and aggressive/dominant behavior in
      humans. However, results about the effects of competitive outcomes are quite
      heterogeneous, suggesting that personal and contextual factors play a moderating
      role in this relationship. To further explore these dimensions, we aimed to
      examine (i) the effect of competition and its outcome on the psychobiological
      response to a laboratory competition in young men, and (ii) the moderating role
      of some cognitive dimensions such as causal attributions. To do so, we compared
      the responses of 56 healthy young men faced with two competitive tasks with
      different instructions. Twenty-eight men carried out a task whose instructions
      led subjects to think the outcome was due to their personal performance ("merit"
      task), whereas 28 other men faced a task whose outcome was attributable to luck
      ("chance" task). In both cases, outcome was manipulated by the experimenter.
      Salivary steroid hormones (testosterone and cortisol), cardiovascular variables
      (heart rate and blood pressure), and emotional state (mood and anxiety) were
      measured at different moments before, during and after both tasks. Our results
      did not support the "winner-loser effect" because no significant differences were
      found in the responses of winners and losers. However, significantly higher
      values on the testosterone and cardiovascular variables, along with slight
      decreases in positive mood, were associated with the merit-based competition, but
      not the chance-based condition. In addition, an exploratory factorial analysis
      grouped the response components into two patterns traditionally related to more
      active or more passive behaviors. Thus, our results suggest that the perception
      of contributing to the outcome is relevant in the psychobiological response to
      competition in men. Overall, our results reveal the importance of the appraisal
      of control and causal attribution in understanding human competitive
      interactions.

PMID- 28433518
TI  - Efficacy of tranexamic acid on side effects of rhinoplasty: A randomized double
      blind study.
AB  - INTRODUCTION: The aim of this randomized double-blind study was to evaluate the
      efficacy of Tranexamic acid (TXA) on intraoperative bleeding, postoperative
      eyelid edema, and postoperative periorbital ecchymosis in rhinoplasty. MATERIALS
      AND METHODS: Sixty rhinoplasty patients who needed hump reduction and lateral
      osteotomy were included and then randomly assigned into two groups. In the
      intervention group (n = 30), 10 mg/kg of TXA was administered prior to the
      operation and in the control group, the patients were given 20 mL of normal
      saline. Intraoperative bleeding was evaluated by gravimetric method and pre and
      postoperative hemoglobin and hematocrit levels were determined. Eyelid edema and
      periorbital ecchymosis were evaluated using 0-4 points scoring system. Surgeon
      satisfaction was measured by asking questions of the surgeon. Data were analyzed
      by SPSS 20.0 (P < 0.05). RESULTS: In total, 10 participants were excluded from
      the research, and 50 patients were included in the study. Mean (SD) of
      intraoperative bleeding was 213 (65) mL and 254 (55) mL in the intervention and
      control group, respectively, based on the clinical methods (P = 0.013). Level of
      hemoglobin was 266.69 in the control group versus 241.25 in the TXA group,
      indicating that this effect on the intraoperative bleeding was not significant (P
      = 0.1). Hematocrit differences before and after operation were significant (P =
      0.03) (247.06 mL in TXA vs. 279.2 mL in the control group). TXA had a
      statistically significant effect on the eyelid edema (P = 0.03), periorbital
      ecchymosis (P = 0.04), and surgeon satisfaction (P = 0.03). CONCLUSION:
      Administration of 10 mm/kg TXA had a significant effect in decreasing the
      intraoperative bleeding rate, eyelid edema, and periorbital ecchymosis in the
      rhinoplasty with minimal side effects.

PMID- 28433519
TI  - Patients' Use and Evaluation of an Online System to Annotate Radiology Reports
      with Lay Language Definitions.
AB  - RATIONALE AND OBJECTIVES: The increasing availability of personal health portals
      has made it easier for patients to obtain their imaging results online. However,
      the radiology report typically is designed to communicate findings and
      recommendations to the referring clinician, and may contain many terms unfamiliar
      to lay readers. We sought to evaluate a web-based interface that presented
      reports of knee MRI (magnetic resonance imaging) examinations with annotations
      that included patient-oriented definitions, anatomic illustrations, and
      hyperlinks to additional information. MATERIALS AND METHODS: During a 7-month
      observational trial, a statement added to all knee MRI reports invited patients
      to view their annotated report online. We tracked the number of patients who
      opened their reports, the terms they hovered over to view definitions, and the
      time hovering over each term. Patients who accessed their annotated reports were
      invited to complete a survey. RESULTS: Of 1138 knee MRI examinations during the
      trial period, 185 patients (16.3%) opened their report in the viewing portal. Of
      those, 141 (76%) hovered over at least one term to view its definition, and 121
      patients (65%) viewed a mean of 27.5 terms per examination and spent an average
      of 3.5 minutes viewing those terms. Of the 22 patients who completed the survey,
      77% agreed that the definitions helped them understand the report and 91% stated
      that the illustrations were helpful. CONCLUSIONS: A system that provided
      definitions and illustrations of the medical and technical terms in radiology
      reports has potential to improve patients' understanding of their reports and
      their diagnoses.

PMID- 28433520
TI  - Corrigendum to "Therapeutic effect of ursolic acid in experimental visceral
      leishmaniasis" [Int. J. Parasitol. Drugs Drug Resist. 7 (2017) 1-11].

PMID- 28433521
TI  - Determination of cyclopeptide toxins in Amanita subpallidorosea and Amanita
      virosa by high-performance liquid chromatography coupled with high-resolution
      mass spectrometry.
AB  - Amanita subpallidorosea is a recently discovered lethal Amanita sect. Phalloideae
      species found in China that is clustered with A. virosa in the same clade based
      on molecular phylogenetic analysis. However, the cyclopeptide toxin contents of
      these lethal mushrooms remain poorly studied. In this study, the cyclopeptide
      toxins in A. subpallidorosea were reported for the first time and the
      cyclopeptide compositions of A. subpallidorosea and A. virosa species were
      systematically analyzed. Thirteen cyclopeptides and two unknown compounds were
      identified or observed from these two lethal mushrooms by high-performance liquid
      chromatography coupled with high-resolution mass spectrometry. Of the known
      cyclopeptides, the virotoxins alaviroidin, viroisin, and viroidin, which were
      previously thought to be restricted to A. virosa, were identified in A.
      subpallidorosea. The cyclopeptide compositions showed that there are diversities
      in the kinds and levels of amatoxins, phallotoxins, and virotoxins between A.
      subpallidorosea and A. virosa species, and that the amount of total toxins in the
      tested A. subpallidorosea is significantly higher than that in the tested A.
      virosa. Furthermore, consistency of the cyclopeptide toxins with the molecular
      phylogenetic relationships was demonstrated.

PMID- 28433522
TI  - Metaphors for human diseases.

PMID- 28433523
TI  - Association of preresidency peer-reviewed publications with radiation oncology
      resident choice of academic versus private practice career.
AB  - INTRODUCTION: The decision of radiation oncology residents to pursue academic
      versus private practice careers plays a central role in shaping the present and
      future of the field, but factors that are potentially predictive of this decision
      are lacking. This study was performed to examine the role of several factors
      publicly available before residency on postresidency career choice, including
      preresidency peer-reviewed publications (PRPs), which have been associated with
      resident career choice in comparably competitive subspecialties such as
      neurosurgery. METHODS AND MATERIALS: Using a combination of Internet searches,
      telephone interviews, and the 2015 Association of Residents in Radiation Oncology
      directory, a list of 2016 radiation oncology resident graduates was compiled,
      along with their postresidency career choice. PRP was defined as the number of
      PubMed publications encompassing the end of the calendar year (2010) in which
      residency applications were due; this number was then correlated with career
      choice. RESULTS: A total of 163 residents from 76 Accreditation Council for
      Graduate Medical Education-certified programs were examined: 78% were male, 22%
      were MDs/PhDs, and 79 graduates (48%) chose academic careers. Fifty-two percent
      of graduates had at least 1 PRP at the time of application to radiation oncology
      residency; 35% had more than 1 PRP. Regarding career choice, the difference
      between 0 and 1+ PRP was statistically significant (odds ratio, 3.3; P < .01),
      but not between 1 and >1 PRP. Sex, PhD, or non-PhD dual degree status were not
      associated with career choice. CONCLUSIONS: Radiation oncology residency
      graduates with 1 or more PRPs at the time of residency application were roughly 2
      times more likely to choose an academic career as their initial career choice
      than graduates with no preresidency PRPs. This information may prove useful to
      medical students, medical school advisors, and residency program directors and
      deserves further prospective investigation.

PMID- 28433524
TI  - An analysis of knowledge-based planning for stereotactic body radiation therapy
      of the spine.
AB  - PURPOSE: Planning for spine stereotactic body radiation therapy (SBRT) is time
      consuming, and differences in planner experience and technique result in
      discrepancies in plan quality between facilities. Here, knowledge-based planning
      is analyzed to determine if it may be effective in improving the quality and
      efficiency of spine SBRT planning. MATERIALS AND METHODS: Thirty-eight spine SBRT
      cases were collected from the University of Michigan database and inverse planned
      to deliver 3 10-Gy fractions to the planning target volume (PTV). These plans
      were used to train a knowledge-based model (model A) using RapidPlan (Varian
      Medical Systems). The model was evaluated for outliers and validated in 10
      independent cases. Each of these cases was manually planned to compare the
      quality of the model-generated plans with the manual plans. To further test the
      robustness of the software, 2 additional models (models B and C) were created
      with intentional outliers resulting from inconsistent contouring. RESULTS: Using
      models A, B, and C, all 10 generated plans met all dose objectives for modeled
      organs at risk (OARs) (spinal cord, cord planning risk volume, and esophagus)
      without user intervention. The target coverage and OAR dose sparing was improved
      or equivalent to manual planning by an expert dosimetrist; however, manually
      created plans typically required 1 to 1.5 hours to produce and model-generated
      plans required only 10 to 15 minutes with minimal human intervention to meet all
      dose objectives. CONCLUSIONS: The clinical quality of plans produced by RapidPlan
      were found to improve on or be similar to the manually created plans in terms of
      normal tissue objectives and PTV dose coverage and could be produced in a
      fraction of the time. RapidPlan is a robust technique that can improve planning
      efficiency in spine SBRT while maintaining or potentially improving plan quality
      and standardization across planners and centers.

PMID- 28433526
TI  - Orkambi in patients with severe disease - Bumps in the road to CFTR modulation.

PMID- 28433525
TI  - [Should we think hypercalcaemia?]

PMID- 28433527
TI  - Characterization of leukocyte subsets in buffalo (Bubalus bubalis) with cross
      reactive monoclonal antibodies specific for bovine MHC class I and class II
      molecules and leukocyte differentiation molecules.
AB  - Although buffaloes (Bubalus bubalis) are a major component of the livestock
      industry worldwide, limited progress has been made in the study of the mechanisms
      regulating the immune response to pathogens and parasites affecting their health
      and productivity. This has been, in part, attributable to the limited
      availability of reagents to study immune responses in buffalo. As reported here,
      a set of cross-reactive monoclonal antibodies (mAbs), developed against bovine,
      ovine and caprine leukocyte differentiation molecules (LDM) and major
      histocompatibility complex (MHC) molecules, were identified and used to compare
      expression of LDM in Italian and Egyptian buffalo. The results show most of the
      epitopes identified with the mAbs are conserved on LDM and MHC I and II molecules
      in both lineages of buffalo. Comparison of the composition of lymphocyte subsets
      between buffalo and cattle revealed they are similar except for expression of CD2
      and CD8 on workshop cluster one (WC1) positive gammadelta T cells. In cattle, CD8
      is expressed on a subset of CD2+/WC1- gammadelta T cells that are present in low
      frequency in blood of young and old animals, whereas, CD8-/CD2-/WC1+ gammadelta T
      cells are present in high frequency in young animals, decreasing with age. In the
      buffalo, CD2 is expressed on a subset of WC1+ gammadelta T cells and CD8 is
      expressed on all WC1+ gammadelta T cells. The availability of this extensive set
      of mAbs provides opportunities to study the immunopathogenesis of pathogens and
      parasites affecting the health of buffalo.

PMID- 28433528
TI  - Evolutionary history of the T cell receptor complex as revealed by small-spotted
      catshark (Scyliorhinus canicula).
AB  - In every jawed vertebrate species studied so far, the T cell receptor (TCR)
      complex is composed of two different TCR chains (alpha/beta or gamma/delta) and a
      number of CD3 subunits responsible for transmitting signals into the T cell. In
      this study, we characterised all of the TCR and CD3 genes of small-spotted
      catshark (Scyliorhinus canicula) and analysed their expression in a broad range
      of tissues. While the TCR complex is highly conserved across jawed vertebrates,
      we identified a number of differences in catshark, most notably the presence of
      two copies of both TCRbeta and CD3gammadelta, and the absence of a functionally
      important proline rich region from CD3epsilon. We also demonstrate that TCRbeta
      has duplicated independently multiple times in jawed vertebrate evolution,
      bringing additional diversity to the TCR complex. This study reveals new insights
      about the evolutionary history of the TCR complex and raises new avenues for
      future exploration.

PMID- 28433529
TI  - Antimicrobial peptides within the Yellowtail Kingfish (Seriola lalandi).
AB  - A number of Seriola species are currently farmed or being investigated as future
      aquaculture species in countries around the world. However they face a number of
      issues and limitations which will need to be overcome to ensure future stability
      and growth, one of which are disease outbreaks. Despite this, very little has
      been done to understand the immune system of Seriola species and very few immune
      genes have been characterised. Antimicrobial peptides (AMP) are naturally
      occurring low molecular weight polypeptides that play a major role in an
      organism's immune system and act effectively as a first line of defence. This
      investigation isolates the full length cDNA sequences of two AMP's, piscidin and
      hepcidin from the yellowtail kingfish (Seriola lalandi). The full-length cDNA of
      the piscidin gene encodes a 65 amino acid prepropeptide, containing a 25-residue
      peptide, predicted to form an amphipathic helix-loop-helix structure.
      Phylogenetic analysis using fish piscidin sequences, showed that this AMP is only
      found in bony fish within the Acanthomorpha clade and that a possible three
      groups within the piscidin family exists, with S. lalandi belonging to a
      particular group. The full-length cDNA of the hepcidin gene encodes a 90 amino
      acid preprohepcidin, which contains a typical RX(R/K)R motif for cleavage of the
      mature peptide which comprises of eight conserved cysteine residues. Phylogenetic
      analysis of known vertebrate hepcidin antimicrobial peptide (HAMP) sequences,
      shows sequences from the Neoteleostei clade of bony fish form two very separate
      groups, HAMP1 and HAMP2, with the S. lalandi hepcidin gene grouped with the HAMP1
      sequences. HAMP2 sequences are found to have multiple copies within fish and
      genome analysis showed very clearly that these two groups of genes are located on
      separate regions on the genome, with the multiple HAMP2 copies formed from tandem
      gene duplications. Lastly, using qPCR the expression of the S. lalandi piscidin
      gene within healthy fish was highest within, spleen and gills and lowest in
      liver, whereas hepcidin was highest in the liver with little or no expression in
      the spleen and gills.

PMID- 28433530
TI  - In memory of Professor Brian F. C. Clark: Tribute by Mike Taussig, Editor in
      Chief, New Biotechnology.

PMID- 28433531
TI  - Discovery and optimization of selective FGFR4 inhibitors via scaffold hopping.
AB  - Introduction of a Michael acceptor on a flexible scaffold derived from pan-FGFR
      inhibitors has successfully yielded a novel series of highly potent FGFR4
      inhibitors with selectivity over FGFR1. Due to reduced lipophilicity and aromatic
      ring count, this series demonstrated improved solubility and permeability.
      However, plasma instability and fast metabolism limited its potential for in vivo
      studies. Efforts have been made to address these problems, which led to the
      discovery of compound (-)-11 with improved stability, CYP inhibition, and good
      activity/selectivity for further optimization.

PMID- 28433533
TI  - Corrigendum to "Development of SERS substrate using phage-based magnetic template
      for triplex assay in sepsis diagnosis" [Biosens. Bioelectron. 85 (2016) 522-528].

PMID- 28433532
TI  - EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for
      tumor imaging.
AB  - Chemical Exchange Saturation Transfer (CEST) approach is a novel tool within
      magnetic resonance imaging (MRI) that allows visualization of molecules
      possessing exchangeable protons with water. Many molecules, employed as
      excipients for the formulation of finished drug products, are endowed with
      hydroxyl, amine or amide protons, thus can be exploitable as MRI-CEST contrast
      agents. Their high safety profiles allow them to be injected at very high doses.
      Here we investigated the MRI-CEST properties of several excipients (ascorbic
      acid, sucrose, N-acetyl-d-glucosamine, meglumine and 2-pyrrolidone) and tested
      them as tumor-detecting agents in two different murine tumor models (breast and
      melanoma cancers). All the investigated molecules showed remarkable CEST contrast
      upon i.v. administration in the range 1-3ppm according to the type of mobile
      proton groups. A marked increase of CEST contrast was observed in tumor regions
      up to 30min post injection. The combination of marked tumor contrast enhancement
      and lack of toxicity make these molecules potential candidates for the diagnosis
      of tumors within the MRI-CEST approach.

PMID- 28433534
TI  - Effect of surface energy of solid surfaces on the micro- and macroscopic
      properties of adsorbed BSA and lysozyme.
AB  - The surface energy, a macroscopic property, depends on the chemical functionality
      and micro- and macroscopic roughness of the surface. The adsorption of two widely
      used proteins bovine serum albumin (BSA) and lysozyme on surfaces of four
      different chemical functionalities were done to find out the interrelation
      between macroscopic and microscopic properties. We have observed the secondary
      structure of protein after its adsorption. In addition, we observed the variation
      of surface energy of proteins due to variation in adsorption time, change in
      protein concentration and effect of a mixture of proteins. Surfaces of three
      different chemical functionalities namely, amine, hydroxyl and octyl were
      obtained through self-assembled monolayer on silica surfaces and were tested for
      responses towards adsorption of lysozyme and BSA. The adsorbed lysozyme has
      higher surface energy than the adsorbed BSA on amine and octyl surfaces. On
      hydroxyl functional surface, the surface energy due to the adsorbed lysozyme or
      BSA increases slowly with time. The surface energy of the adsorbed protein
      increases gradually with increasing protein concentration on hydrophobic
      surfaces. On hydrophilic surfaces, with increasing BSA concentration in bulk
      solution, the surface energy of the adsorbed protein on GPTMS and amine surfaces
      is maximum at 1MUM concentration. During the adsorption from a mixture of BSA and
      lysozyme on octyl surface, first lysozyme adsorbs and subsequent BSA adsorption
      leads to a high surface energy.

PMID- 28433535
TI  - Bioimaging and biodetection assisted with TTA-UC materials.
AB  - Upconversion of light has attracted intensive studies for biomedical research,
      because it enables deeper tissue analysis owing to the longer wavelength of
      incident light, compared with conventional downconversion fluorescent materials.
      Triplet-triplet annihilation (TTA), as a typical mechanism of upconversion, does
      not necessitate high power excitation and exhibits a higher quantum yield than
      rare earth upconversion owing to more sensitizer options with higher absorption
      coefficients. A desirable wavelength range of excitation and emission can be
      realized by careful selection of the combination of sensitizer and activator.
      Therefore, TTA-UC is worth exploring further for biorelated applications, such as
      bioimaging and biodetection. Recent developments are reviewed in this article.

PMID- 28433536
TI  - Assessment of enamel cracks at adhesive cavosurface margin using three
      dimensional swept-source optical coherence tomography.
AB  - OBJECTIVES: Swept-source optical coherence tomography (SS-OCT) can construct
      cross-sectional images of internal biological structures. The aim of this study
      was to evaluate enamel cracks at the cavosurface margin of composite restorations
      using SS-OCT. METHODS: Bowl-shaped cavities were prepared at two locations (mid
      coronal and cervical regions) on the enamel surface of 60 bovine teeth. Half of
      the cavities (30) were treated with phosphoric acid gel. A two-step self-etch
      adhesive (Clearfil SE Bond) was applied to all cavities and a flowable composite
      was placed in bulk. After 7days in water at 37 degrees C, three-dimensional (3D)
      images of the specimens were obtained using SS-OCT, and cross-sectional views of
      the cavosurface margin were examined. Presence and extent of enamel cracks along
      the cavosurface margin circumference were evaluated using a 5-point scale. The
      results were statistically compared with Wilcoxon rank sum test with Bonferroni
      correction. RESULTS: 3D SS-OCT could detect enamel cracks at the cavosurface
      margin of composite restorations. Cervical regions caused more enamel cracking
      than mid-coronal regions. Phosphoric acid etching increased the incidence of
      enamel cracks compared with the preparations without etching. CONCLUSION: SS-OCT
      can be used to detect enamel cracks at the margins of composite restorations
      noninvasively. Presence and extent of enamel cracks depended on the enamel region
      and bonding protocol. CLINICAL SIGNIFICANCE: SS-OCT can be used to detect enamel
      cracks at the margins of composite restorations noninvasively. Selective
      phosphoric acid etching of the enamel significantly increased the incidence of
      marginal cracks, especially in cervical preparation.

PMID- 28433537
TI  - A Personal Perspective: My Four Encounters with John Kendrew.
AB  - By celebrating the 100th anniversary of John Kendrew's birth in 1917, the Journal
      of Molecular Biology recognizes his seminal contributions to science in general
      and structural biology in particular. John was first to use X-ray diffraction to
      solve the 3-dimensional structure of a protein, sperm-whale myoglobin, worthy of
      a Nobel Prize in Chemistry in 1962. John was the Founder and first Editor-in
      Chief of the Journal of Molecular Biology, Deputy Chairman of the Laboratory of
      Molecular Biology and Head of its Division of Structural Studies, a Founder of
      the European Molecular Biology Organization, first Director-General of the
      European Molecular Biology Laboratory, and 33rd President of St. John's College,
      Oxford. In this personal perspective I relate how I came to know John as his
      postdoctoral fellow at the Laboratory of Molecular Biology in 1967 and as his
      biographer 45 years later.

PMID- 28433538
TI  - The NS1 Protein from Influenza Virus Stimulates Translation Initiation by
      Enhancing Ribosome Recruitment to mRNAs.
AB  - The non-structural protein NS1 of influenza A viruses exerts pleiotropic
      functions during infection. Among these functions, NS1 was shown to be involved
      in the control of both viral and cellular translation; however, the mechanism by
      which this occurs remains to be determined. Thus, we have revisited the role of
      NS1 in translation by using a combination of influenza infection, mRNA reporter
      transfection, and in vitro functional and biochemical assays. Our data show that
      the NS1 protein is able to enhance the translation of virtually all tested mRNAs
      with the exception of constructs bearing the Dicistroviruses Internal ribosome
      entry segment (IRESes) (DCV and CrPV), suggesting a role at the level of
      translation initiation. The domain of NS1 required for translation stimulation
      was mapped to the RNA binding amino-terminal motif of the protein with residues
      R38 and K41 being critical for activity. Although we show that NS1 can bind
      directly to mRNAs, it does not correlate with its ability to stimulate
      translation. This activity rather relies on the property of NS1 to associate with
      ribosomes and to recruit them to target mRNAs.

PMID- 28433539
TI  - Rationally Designed PI3Kalpha Mutants to Mimic ATR and Their Use to Understand
      Binding Specificity of ATR Inhibitors.
AB  - ATR, a protein kinase in the PIKK family, plays a critical role in the cell DNA
      damage response and is an attractive anticancer drug target. Several potent and
      selective inhibitors of ATR have been reported showing significant antitumor
      efficacy, with most advanced ones entering clinical trials. However, due to the
      absence of an experimental ATR structure, the determinants contributing to ATR
      inhibitors' potency and specificity are not well understood. Here we present the
      mutations in the ATP-binding site of PI3Kalpha to progressively transform the
      pocket to mimic that of ATR. The generated PI3Kalpha mutants exhibit
      significantly improved affinity for selective ATR inhibitors in multiple chemical
      classes. Furthermore, we obtained the X-ray structures of the PI3Kalpha mutants
      in complex with the ATR inhibitors. The crystal structures together with the
      analysis on the inhibitor affinity profile elucidate the roles of individual
      amino acid residues in the binding of ATR inhibitors, offering key insights for
      the binding mechanism and revealing the structure features important for the
      specificity of ATR inhibitors. The ability to obtain structural and binding data
      for these PI3Kalpha mutants, together with their ATR-like inhibitor binding
      profiles, makes these chimeric PI3Kalpha proteins valuable model systems for
      structure-based inhibitor design.

PMID- 28433540
TI  - ER-alpha36 Interactions With Cytosolic Molecular Network in Acquired Tamoxifen
      Resistance.
AB  - According to the World Health Organization (WHO) published data in 2015; breast
      cancer is the most prevalent and the second leading cause of cancer death among
      females. As approximately 70% of breast cancer tumor cells are estrogen receptor
      (ER) positive, primary therapeutic agents such as Anti-estrogens were produced
      mostly in a way to target this receptor. Anti-estrogen therapies mostly target
      Estrogen receptor and block its underlying signaling pathways. Nevertheless,
      resistance to these agents made the condition more complicated. Recently the role
      of one molecule in the resistance development has been studied in some cases: ER
      alpha36 is a 36 kDa variant of estrogen receptor molecule which is mostly absent
      in normal breast cells. Its interactions with epidermal growth factor receptors
      and ER-alpha66 leads in over-activation and/or over-expression of estrogen
      independent pathways and suppression of estrogen-dependent pathways; they all in
      turn, will maintain tumor cell's growth even in the presence of tamoxifen. In
      this mini-review, we mainly surveyed different pathways which ER-alpha36 could
      lead to tamoxifen resistance. We also briefly mentioned how ER-alpha36 could
      switch the growth cascades from estrogen dependent into independent and make this
      resistance network become even more complicated.

PMID- 28433541
TI  - The Impact of 2013 Updated ASCO/CAP HER2 Guidelines on the Diagnosis and
      Management of Invasive Breast Cancer: A Single-Center Study of 1739 Cases.
AB  - BACKGROUND: The purpose of this study was to determine the impact of revised
      ASCO/CAP 2013 HER2 guidelines on the clinical practice of pathologists and
      oncologists. MATERIALS AND METHODS: Retrospective analysis of 1739 patients with
      invasive breast carcinoma who underwent reflex HER2 (fluorescence in situ
      hybridization [FISH]) testing, using both 2007 and 2013 guidelines (2007-2014).
      RESULTS: Using 2013 guidelines, 255 (15%; 95% confidence interval [CI], 13%-16%)
      cases were classified as HER2+ as opposed to 186 (11%; 95% CI, 9%-12%) by 2007
      guidelines (odds ratio [OR] 1.4; 95% CI, 1.2-1.8; P = .0005). Sixty-nine cases
      equivocal by 2007 guidelines (12% of all equivocal cases) were converted to HER2+
      by 2013 guidelines. Sixty-two of these 69 cases shifted from HER2 equivocal to
      positive due to change in FISH ratio cutoff from 2.2 to 2.0. Six cases had FISH
      ratio < 2.0 but immunohistochemistry (IHC) score 3+ in 10% to 30% of tumor cells.
      One case had FISH ratio of 2.0 and IHC score 3+ in 10% to 30% of tumor cells.
      FISH and IHC test results were discordant in 5% (95% CI, 4%-6%) of cases using
      2013 guidelines. No increase in HER2 FISH equivocal cases was observed. Reflex
      FISH testing of all IHC 1+ cases at our institution additionally detected 58
      patients (5%; 95% CI, 4%-6%) with HER2 amplification. CONCLUSIONS: The 2013
      guidelines increase the detection of HER2+ cases, without introducing significant
      difference in discordance rate of the IHC and FISH assays. Inclusion of HER2 copy
      number criterion does not increase the number of FISH equivocal cases in our
      cohort. We recommend IHC 1+ cases should be offered reflex FISH testing because
      failure to test them will miss a small number (5%) of potentially treatable
      cases.

PMID- 28433543
TI  - Phenformin Inhibits Myeloid-Derived Suppressor Cells and Enhances the Anti-Tumor
      Activity of PD-1 Blockade in Melanoma.
AB  - Biguanides, such as the diabetes therapeutics metformin and phenformin, have
      shown antitumor activity both in vitro and in vivo. However, their potential
      effects on the tumor microenvironment are largely unknown. Here we report that
      phenformin selectively inhibits granulocytic myeloid-derived suppressor cells in
      spleens of tumor-bearing mice and ex vivo. Phenformin induces production of
      reactive oxygen species in granulocytic myeloid-derived suppressor cells, whereas
      the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin.
      Co-treatment of phenformin enhances the effect of anti-PD-1 antibody therapy on
      inhibiting tumor growth in the BRAF V600E/PTEN-null melanoma mouse model.
      Combination of phenformin and anti PD-1 cooperatively induces CD8+ T-cell
      infiltration and decreases levels of proteins that are critical for immune
      suppressive activities of myeloid-derived suppressor cells. Our findings show a
      selective, inhibitory effect of phenformin on granulocytic myeloid-derived
      suppressor cell-driven immune suppression and support that phenformin improves
      the anti-tumor activity of PD-1 blockade immunotherapy in melanoma.

PMID- 28433544
TI  - Birth Outcomes in Children Fathered by Men Treated with Immunosuppressant Drugs
      before Conception-A Danish Population-Based Cohort Study.

PMID- 28433545
TI  - Authors' Reply to Twycross.

PMID- 28433542
TI  - Blockade of PDGF Receptors by Crenolanib Has Therapeutic Effect in Patient
      Fibroblasts and in Preclinical Models of Systemic Sclerosis.
AB  - Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment
      options. Activated fibroblasts are the key effector cells in SSc responsible for
      the excessive production of collagen and the development of fibrosis. Platelet
      derived growth factor (PDGF), a potent mitogen for cells of mesenchymal origin,
      has been implicated in the activation of SSc fibroblasts. Our aim was to examine
      the therapeutic potential of crenolanib, an inhibitor of PDGF receptor signaling,
      in cultured fibroblasts and in angiotensin II-induced skin and heart fibrosis.
      Crenolanib effectively inhibited proliferation and migration of SSc and healthy
      control fibroblasts and attenuated basal and transforming growth factor-beta
      induced expression of CCN2/CTGF and periostin. In contrast to healthy control
      fibroblasts, SSc fibroblasts proliferated in response to PDGFAA, whereas a
      combination of PDGFAA and CCN2 was required to elicit a similar response in
      healthy control fibroblasts. PDGF receptor alpha mRNA correlated with CCN2 and
      other fibrotic markers in the skin of SSc patients. In mice challenged with
      angiotensin II, PDGF receptor alpha-positive cells were increased in the skin and
      heart. These PDGF receptor alpha-positive cells co-localized with PDGF receptor
      beta, procollagen, and periostin. Treatment with crenolanib attenuated the skin
      and heart fibrosis. Our data indicate that inhibition of PDGF signaling presents
      an attractive therapeutic approach for SSc.

PMID- 28433546
TI  - Symptom Trajectories in Children Receiving Treatment for Leukemia: A Latent Class
      Growth Analysis With Multitrajectory Modeling.
AB  - CONTEXT: Cancer treatment symptoms play a major role in determining the health of
      children with cancer. Symptom toxicity often results in complications, treatment
      delays, and therapy dose reductions that can compromise leukemia therapy and
      jeopardize chances for long-term survival. Critical to understanding symptom
      experiences during treatment is the need for exploration of "why" inter
      individual symptom differences occur; this will determine who may be most
      susceptible to treatment toxicities. OBJECTIVES: This study examined specific
      symptom trajectories during the first 18 months of childhood leukemia treatment.
      Symptom measures included fatigue, sleep disturbances, pain, nausea, and
      depression. METHODS: Symptom trajectories of 236 children with leukemia three to
      18 years old were explored prospectively over four periods: initiation of post
      induction therapy, four and eight post-induction therapy, and the last time point
      was at the beginning of maintenance/continuation therapy. Latent class growth
      analysis was used to classify patients into distinctive groups with similar
      symptom trajectories based on patients' response patterns on the symptom measures
      over time. RESULTS: Three latent classes of symptom trajectories were identified
      and classified into mild, moderate, and severe symptom trajectories. The only
      demographic characteristic with a significant relationship to membership in the
      latent class symptom trajectories was race/ethnicity. All other demographic
      characteristics including leukemia risk levels showed no significant
      relationships. CONCLUSION: This study is unique in that groups of patients with
      similar symptoms were identified rather than groups of symptoms. Further research
      using latent class growth analysis is needed.

PMID- 28433547
TI  - Sodium Valproate as a Continuous Subcutaneous Infusion: A Case Series.

PMID- 28433548
TI  - Effects of Sex and Education on Cognitive Change Over a 27-Year Period in Older
      Adults: The Rancho Bernardo Study.
AB  - OBJECTIVE: This study investigated how cognitive function changes with age and
      whether rates of decline vary by sex or education in a large, homogenous
      longitudinal cohort characterized by high participation rates, long duration of
      follow-up, and minimal loss to follow-up. DESIGN/SETTING/PARTICIPANTS: Between
      1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo
      Study, aged 31 to 99 years at their initial cognitive assessment, completed
      neuropsychological testing approximately every 4 years, over a maximum 27-year
      follow-up. MEASUREMENTS: Linear mixed effects regression models defined sex
      specific cognitive trajectories, adjusting for education and retest effects.
      RESULTS: Significant decline across all cognitive domains began around age 65
      years and accelerated after age 80 years. Patterns of decline were generally
      similar between sexes, although men declined more rapidly than women on the
      global function test. Higher education was associated with slower decline on the
      tests of executive and global functions. After excluding 517 participants with
      evidence of cognitive impairment, accelerating decline with age remained for all
      tests, and women declined more rapidly than men on the executive function test.
      CONCLUSIONS: Accelerating decline with advancing age occurs across multiple
      cognitive domains in community-dwelling older adults, with few differences in
      rates of decline between men and women. Higher education may provide some
      protection against executive and global function decline with age. These findings
      better characterize normal cognitive aging, a critical prerequisite for
      identifying individuals at risk for cognitive impairment, and lay the groundwork
      for future studies of health and behavioral factors that affect age-related
      decline in this cohort.

PMID- 28433550
TI  - Evaluation of a Telephone-Delivered, Community-Based Collaborative Care
      Management Program for Caregivers of Older Adults with Dementia.
AB  - OBJECTIVES: To evaluate whether a community-based, telephone-delivered, brief
      patient/caregiver-centered collaborative dementia care management intervention is
      associated with improved caregiver and care recipient (CR) outcomes. DESIGN:
      Longitudinal program evaluation of a clinical intervention; assessments at
      baseline and 3- and 6-month follow-up. SETTING: General community. PARTICIPANTS:
      Caregivers (N = 440) of older, community-dwelling, low-income CRs prescribed a
      psychotropic medication by a primary care provider who met criteria for dementia
      and were enrolled in the SUpporting Seniors Receiving Treatment And INtervention
      (SUSTAIN) program for older adults. INTERVENTION: Dementia care management versus
      clinical evaluation only. MEASUREMENTS: Perceived caregiving burden and caregiver
      general health (primary outcomes); CR neuropsychiatric symptoms and caregiver
      distress in response to CRs' challenging dementia-related behaviors (secondary
      outcomes). RESULTS: Caregivers were, on average, 64.0 (SD: 11.8) years old and
      62.6% provided care for the CR for 20 or more hours per week. The majority of the
      sample was female (73.2%), non-Hispanic White (90.2%), and spousal caregivers
      (72.5%). Adjusted longitudinal models of baseline and 3- and 6-month data suggest
      that compared with caregivers receiving clinical evaluation only, caregivers
      receiving care management reported greater reductions in burden over time.
      Subgroup analyses also showed statistically significant reductions in caregiver
      reported frequency of CR dementia-related behaviors and caregiver distress in
      response to those symptoms at 3-month follow-up. CONCLUSIONS: A community-based,
      telephone-delivered care management program for caregivers of individuals with
      dementia is associated with favorable caregiver and CR-related outcomes. Findings
      support replication and further research in the impact of tailored, collaborative
      dementia care management programs that address barriers to access and engagement.

PMID- 28433551
TI  - In vitro investigation of metabolic profiling of newly developed topoisomerase
      inhibitors (ethyl fluorescein hydrazones, EtFLHs) in RLMs by LC-MS/MS.
AB  - Metabolic profiling of newly reported five topoisomerase inhibitors namely ethyl
      fluorescein hydrazones (EtFLHs) were studied in rat liver microsomes (RLMs) and
      the data were acquired in a liquid chromatography (LC) ion trap mass
      spectrometry. Hydroxyl group containing EtFLHs derivatives (1-3) were bio
      transformed into hydrolyzed, mono-hydroxylated and hydrolyzed together with mono
      hydroxylated metabolites. On the other hand, nitro and methoxy groups containing
      EtFLHs derivatives (4-5) were bio-transformed into hydrolyzed, hydrolyzed
      together with mono-hydroxylated and azo-reductive metabolites in the presence of
      NADPH. No metabolites were observed in the absence of either NADPH or microsomes
      for the compounds (1-5), indicating a likely involvement of CYP450 enzymes and
      cofactor NADPH in the metabolisms.

PMID- 28433549
TI  - Influence of Negative Life Events and Widowhood on Risk for Dementia.
AB  - OBJECTIVE: The aim of the current study was to examine the effect of negative
      life events and widowhood on the incidence of dementia. METHODS: Data were from
      four Swedish longitudinal cohort studies with a total of nearly 2,000
      participants and 8-25 years of follow-up. Seven stressful events were examined
      for which data were available in all cohorts. Clinical dementia diagnoses were
      made through medical and psychological examinations. Cox proportional hazards
      models were used to estimate the association between life events and dementia,
      adjusting for lifestyle and cardiovascular risk factors. RESULTS: The experience
      of one stressful life event was not associated with dementia incidence, but two
      or more negative life events at baseline predicted higher risk for dementia
      (pooled HR: 2.00). This was most apparent for the incidence of vascular dementia
      (pooled HR: 3.60) but not for Alzheimer disease (pooled HR: 1.29). Moreover,
      persons who were widowed and had experienced one or more negative life events
      were found to have a threefold risk for dementia. CONCLUSION: Widowhood augments
      the effect of negative life events on dementia incidence and negative life events
      specifically increase the risk for vascular dementia.

PMID- 28433552
TI  - Roscovitine attenuates intimal hyperplasia via inhibiting NF-kappaB and STAT3
      activation induced by TNF-alpha in vascular smooth muscle cells.
AB  - Roscovitine is a selective CDK inhibitor originally designed as anti-cancer
      agent, which has also been shown to inhibit proliferation in vascular smooth
      muscle cells (VSMCs). However, its effect on vascular remodeling and its
      mechanism of action remain unknown. In our study, we created a new intimal
      hyperplasia model in male Sprague-Dawley rats by trypsin digestion method, which
      cause to vascular injury as well as the model of rat carotid balloon angioplasty.
      Roscovitine administration led to a significant reduction in neointimal formation
      and VSMCs proliferation after injury in rats. Western blot analysis revealed
      that, in response to vascular injury, TNF-alpha stimulation induced p65 and STAT3
      phosphorylation and promoted translocation of these molecules into the nucleus.
      p65 can physically associate with STAT3 and bind to TNF-alpha-regulated target
      promoters, such as MCP-1 and ICAM-1, to initiate gene transcription. Roscovitine
      can interrupt activation of NF-kappaB and reduce expression of TNF-alpha-induced
      proinflammatory gene, thus inhibiting intimal hyperplasia. These findings provide
      a novel mechanism to explain the roscovitine-mediated inhibition of intimal
      hyperplasia induced by proinflammatory pathways.

PMID- 28433554
TI  - Catheter ablation to prevent sudden cardiac death.
AB  - Since ventricular arrhythmias are a common cause of sudden cardiac death (SCD),
      treatment for ventricular arrhythmias is the target area of interest in research
      field. Among different means to prevent ventricular arrhythmias, catheter
      ablation (CA) has emerged as an effective therapeutic method. CA can decrease the
      likelihood of SCD in the following arrhythmia categories: 1) idiopathic
      ventricular fibrillation (VF) that is usually triggered by premature ventricular
      beats originating in the Purkinje fibres; 2) VF in subjects with structural heart
      disease, especially after myocardial infarction, that is triggered by premature
      ventricular beats from surviving Purkinje fibres; 3) Brugada syndrome in which
      modification of an epicardial substrate in the right ventricular outflow tract
      might be the most promising strategy; 4) recurrent monomorphic ventricular
      tachycardias in the setting of structural heart disease; 5) ventricular
      preexcitation in which CA appears to be a method of choice in high risk patients,
      regardless of the presence or absence of symptoms. In conclusion, CA is a
      therapeutic method that may prevent SCD in different subsets of patients. Better
      understanding of mechanisms and substrates may further improve the rate of
      success and/or broaden such prophylactic indications.

PMID- 28433553
TI  - Identification and validation of microRNAs directly regulating the UDP
      glucuronosyltransferase 1A subfamily enzymes by a functional genomics approach.
AB  - Posttranscriptional repression of UDP-glucuronosyltransferase (UGT) 1A expression
      by microRNAs (miRNAs) may be an important mechanism underlying interindividual
      variability in drug glucuronidation. Furthermore, the UGT1A 3'-UTR shared by all
      UGT1A enzymes is polymorphic, containing three linked SNPs (rs10929303,
      rs1042640, and rs8330) that could influence miRNA binding. The aim of this study
      was to identify the complete complement of miRNAs that could regulate UGT1A
      expression through binding to the reference and/or common variant UGT1A 3'-UTR.
      Luciferase reporter plasmids containing either the reference or variant UGT1A 3'
      UTR were screened against a 2048 human miRNA library to identify those miRNAs
      that decrease luciferase activity by at least 30% when co-transfected into HEK293
      cells. Four novel miRNAs (miR-103b, miR-141-3p, miR-200a-3p, and miR-376b-3p)
      were identified that repressed both reference and variant UGT1A 3'-UTR, while two
      other miRNAs selectively repressed the reference (miR-1286) or variant (miR-21
      3p) 3'-UTR. Deletion and mutagenesis studies confirmed the binding site location
      for each miRNA. rs8330 disrupted miR-1286 binding to the reference UGT1A 3'-UTR,
      while rs10929303 enhanced miR-21-3p binding to the variant 3'-UTR. Transfection
      of miR-21-3p, miR-103b, miR-141-3p, miR-200a-3p, and miR-376b-3p mimics into
      LS180 human intestinal cells showed repression of UGT1A1 and UGT1A6 mediated
      glucuronidation and mRNA without affecting UGT2B7 activity or mRNA. Furthermore,
      transfection of miR-21-3p, miR-141-3p, and miR-200a-3p into primary human
      hepatocytes, repressed UGT1A1 activity and mRNA without affecting CYP3A activity.
      Finally, miR-21-3p and miR-200a-3p expression were negatively correlated with
      UGT1A6 activity and mRNA in human liver samples. Thus, UGT1A is regulated by
      multiple miRNAs with some showing allele-dependent effects.

PMID- 28433555
TI  - Systemic application of sirolimus prevents neointima formation not via a direct
      anti-proliferative effect but via its anti-inflammatory properties.
AB  - BACKGROUND: Systemic treatment with sirolimus, as used for immunosuppression in
      transplant patients, results in markedly low rates of in-stent restenosis. Since
      the underlying mechanisms remain obscure, we aimed to determine the molecular and
      cellular effects of systemic sirolimus treatment on vascular remodeling
      processes. METHODS AND RESULTS: Systemic sirolimus treatment significantly
      reduced smooth muscle cell (SMC) proliferation 14days after wire-induced injury
      and neointima formation 28days after injury in C57BL/6 mice, while simultaneously
      impairing re-endothelialization. Interestingly, in vitro, sirolimus had no direct
      effect on the proliferation of SMC or endothelial cells (EC) at serum
      concentrations observed after systemic application. In contrast, sirolimus
      reduced the adhesion of leukocytes (CD45+) and bone marrow-derived progenitor
      cells (CD34+) to activated EC by down-regulating the adhesion molecules ICAM-1
      and VCAM-1. In addition, sirolimus treatment also significantly reduced the
      upregulation of ICAM-1 and VCAM-1 and the recruitment of monocytic cells (MOMA
      2+) in neointimal lesions in vivo. CONCLUSION: Our findings show that systemic
      sirolimus treatment effectively prevents SMC and EC proliferation in vivo without
      directly affecting these cells. Instead, sirolimus prevents neointima formation
      and re-endothelialization by attenuating the inflammatory response after injury
      with secondary effects on SMC and EC proliferation. Thus, despite a similar net
      effect, the mechanisms of systemic sirolimus treatment are largely different from
      the local effects achieved after application of sirolimus-eluting stents.

PMID- 28433556
TI  - Bolus injections of novel thrombogenic site-targeted fusion proteins comprising
      annexin-V and Kunitz protease inhibitors attenuate intimal hyperplasia after
      balloon angioplasty.
AB  - BACKGROUND: Systemic administrations of conventional antithrombotics reduce
      neointima formation after angioplasty in experimental animals. However, clinical
      translation of these results has not been successful due to high risk for
      bleeding. OBJECTIVES: We sought to determine whether novel annexin-V (ANV)-Kunitz
      protease inhibitor fusion proteins, TAP-ANV and ANV-6L15, can specifically target
      to vascular injury site and limit neointima formation without inducing systemic
      hypo-coagulation in a rat carotid artery balloon angioplasty injury model.
      METHODS: Near infrared imaging was carried out after balloon-injury and injection
      of fluorescent ANV or ANV-6L15 to examine their bio-distributions. For peri
      procedure treatment, TAP-ANV or ANV-6L15 was administered as i.v. boluses 3
      times: 30-minutes before balloon-injury, immediate after procedure, and 120
      minutes post-balloon-injury. For extended treatment, additional i.v. bolus
      injection was given on day-2, day-3 and every other day thereafter. Carotid
      arteries were collected on day-7 and day-14 for analysis. Blood was collected for
      measurement of clotting parameters. RESULTS: Near infrared imaging and
      immunochemistry showed that fluorescent ANV and ANV-6L15 specifically localized
      to injured carotid artery and significant amount of ANV-6L15 remained bound to
      the injured artery after 24-h. Peri-procedure injections of TAP-ANV or ANV-6L15
      resulted in decrease of intima/media ratio by 56%. Extended injections of both
      yielded similar results. Both decreased the expression of PCNA on day-7 and
      increased the expression calponin on day-14 in the intima post-balloon-injury.
      CONCLUSIONS: TAP-ANV and ANV-6L15 can specifically localize to balloon injured
      carotid arteries after i.v. bolus injections, resulting in substantial
      attenuation of intimal hyperplasia without inducing a state of systemic hypo
      coagulation.

PMID- 28433557
TI  - Early changes of left ventricular filling pattern after reperfused ST-elevation
      myocardial infarction and doxycycline therapy: Insights from the TIPTOP trial.
AB  - AIM: Metalloproteinases inhibition by doxycycline reduces cardiac protein
      degradation at extracellular and intracellular level in the experimental model
      ischemia/reperfusion injury. Since both extracellular cardiac matrix and titin
      filaments inside the cardiomyocyte are responsible for the myocardial stiffness,
      we hypothesized that doxycycline could favorably act on left ventricular (LV)
      filling pressures in patients after reperfused acute ST-elevation myocardial
      infarction (STEMI). METHODS AND RESULTS: Seventy-three of 110 patients of the
      TIPTOP trial underwent a 2D-Echo-Doppler on admission, and at pre-discharge and
      at 6-month after a primary PCI for STEMI and LV dysfunction. From admission to
      pre-discharge, LV filling changed from a high filling pressure (HFP) to a normal
      filling pressure (NFP) pattern in 91% of the doxycycline-group, and in 67% of the
      control-group. Conversely, 1% of the doxycycline-group, and 37% of the control
      group changed the LV filling from NFP to HFP pattern. Overall, a pre-discharge
      HFP pattern was present in 4 patients (11%) of the doxycycline-group and in 13
      patients (36%) of the control-group (p=0.025). The evaluation of
      metalloproteinases and their tissue inhibitors plasma concentrations provide
      possible favorable action of doxycycline. On the multivariate analyses, troponine
      I peak (p=0.026), doxycycline (p=0.033), and on admission to pre-discharge LVEF
      changes (p=0.044) were found to be associated with pre-discharge HFP pattern.
      Independently of their baseline LV filling behavior, the 6-month remodeling was
      less in patients with pre-discharge NFP pattern than in patients with HFP
      pattern. CONCLUSIONS: In patients with STEMI and LV dysfunction doxycycline can
      favorably modulate the LV filling pattern early after primary PCI.

PMID- 28433558
TI  - Spatial relationship of organized rotational and focal sources in human atrial
      fibrillation to autonomic ganglionated plexi.
AB  - BACKGROUND: One approach to improve ablation for atrial fibrillation (AF) is to
      focus on physiological targets including focal or rotational sources or
      ganglionic plexi (GP). However, the spatial relationship between these potential
      mechanisms has never been studied. We tested the hypothesis that rotors and focal
      sources for AF may co-localize with ganglionated plexi (GP). METHODS: We
      prospectively identified locations of AF rotors and focal sources, and correlated
      these to GP sites in 97 consecutive patients (age 59.9+/-11.4, 73% persistent
      AF). AF was recorded with 64-pole catheters with activation/phase mapping, and
      related to anatomic GP sites on electroanatomic maps. RESULTS: AF sources arose
      in 96/97 (99%) patients for 2.6+/-1.4 sources per patient (left atrium: 1.7+/-0.9
      right atrium: 1.1+/-0.8), each with an area of 2-3cm2. On area analyses, the
      probability of an AF source randomly overlapping a GP area was 26%. Left atrial
      sources were seen in 94 (97%) patients, in whom >=1 source co-localized with GP
      in 75 patients (80%; p<0.05). AF sources were more likely to colocalize with left
      vs right GPs (p<0.05), and colocalization was more likely in patients with higher
      CHADS2VASc scores (age>65, diabetes; p<0.05). CONCLUSIONS: This is the first
      study to demonstrate that clinically detected AF focal and rotational sources in
      the left atrium often colocalize with regions of autonomic innervation. Studies
      should define if the role of AF sources differs by their anatomical location.

PMID- 28433560
TI  - Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with
      glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin
      plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial
      including 6-month extension).
AB  - AIMS: To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla
      100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and
      oral anti-hyperglycaemic drugs over 12 months. METHODS: EDITION JP 2 was a
      randomised, open-label, phase 3 study. Following a 6-month treatment period,
      participants continued receiving previously assigned once daily Gla-300 or Gla
      100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period.
      Glycaemic control, hypoglycaemia and adverse events were assessed. RESULTS: The
      12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable
      reasons for discontinuation. Mean HbA1c decrease from baseline to month 12 was
      0.3% in both groups. Annualised rates of confirmed (<=3.9mmol/L [<=70mg/dL]) or
      severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00
      05:59h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24h]:
      rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of
      hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles
      were comparable between treatments. CONCLUSION: Over 12 months, Gla-300-treated
      participants achieved sustained glycaemic control and experienced less
      hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results.

PMID- 28433559
TI  - The KCNH2-IVS9-28A/G mutation causes aberrant isoform expression and hERG
      trafficking defect in cardiomyocytes derived from patients affected by Long QT
      Syndrome type 2.
AB  - BACKGROUND: Long QT Syndrome type 2 (LQT2) is caused by mutations in the KCNH2
      gene that encodes for the alpha-subunit (hERG) of the ion channel conducting the
      rapid delayed rectifier potassium current (IKr). We have previously identified a
      disease causing mutation (IVS9-28A/G) in the branch point of the splicing of
      KCNH2 intron 9. However, the mechanism through which this mutation causes the
      disease is unknown. METHODS AND RESULTS: We generated human induced pluripotent
      stem cell-derived cardiomyocytes (iPSC-CMs) from fibroblasts of two IVS9-28A/G
      mutation carriers. IVS9-28A/G iPSC-CMs showed prolonged repolarization time,
      mimicking what observed at the ECG level in the same patients. The expression of
      the full-length ERG1a isoform resulted reduced, whereas the C-terminally
      truncated ERG1aUSO isoform was upregulated in mutant iPSC-CMs, with consequent
      alteration of the physiological ERG1aUSO/ERG1a ratio. Importantly, we observed an
      impairment of hERG trafficking to the cell membrane. The severity of the
      alterations in hERG expression and trafficking correlated with the clinical
      severity of the disease in the two patients under study. Finally, we were able to
      revert the trafficking defect and reduce the repolarization duration in LQT2 iPSC
      CMs using the proteasome inhibitor ALLN. CONCLUSION: Our results highlight the
      key role of the KCNH2 intron 9 branch point in the regulation of KCNH2 isoform
      expression and hERG channel function, and allow to categorize the IVS9-28A/G
      mutation as LQT2 class 2 mutation. These findings may result in a more
      personalized clinical management of IVS9-28A/G mutation carriers.

PMID- 28433561
TI  - Catheter ablation for acute management of electrical storm in ICD recipients: Is
      it prime time?

PMID- 28433562
TI  - Characterization of the complete mitochondrial genome of Khawia sinensis belongs
      among platyhelminths, cestodes.
AB  - Khawia sinensis is an important species in freshwater fish causing considerable
      economic losses to the breeding industry. This is the first mt genome of a
      caryophyllidean cestode characterised. The entire mt genome of K. sinensis is
      13,759 bp in length. This mt genome contains 12 protein-coding genes, 22 transfer
      RNA genes, two ribosomal RNA genes and two non-coding regions. The arrangement of
      the K. sinensis mt genome is the same as other tapeworms, however, the incomplete
      stop codon (A) is more frequent that other species. Phylogenetic analyses based
      on concatenated amino-acid sequences of the 12 protein-coding genes of 17
      tapeworms including K. sinensis were conducted to assess the relationship of K.
      sinensis with other species, the result indicated K. sinensis was closely related
      with cestode species. This complete mt genome of K. sinensis will enrich the
      mitochondrial genome databases of tapeworms and provide important molecular
      markers for ecology, diagnostics, population variation and evolution of K.
      sinensis and other species.

PMID- 28433564
TI  - Recognising the role of community-directed treatment and of women in the fight
      against NTDs.

PMID- 28433563
TI  - Aryl thiosemicarbazones: In vitro and immunomodulatory activities against L.
      amazonensis.
AB  - Leishmaniasis is an infection caused by different species of Leishmania genus.
      Currently, there is no vaccine available for Leishmania infections in humans and
      conventional treatments are limited due to side effects. Therefore, the
      development of new antileishmanial drugs is an urgent need. In present study, we
      evaluated the cytotoxicity in host cells, leishmanicidal activity and
      immunomodulatory potential of seven aryl thiosemicarbazones. Host cell
      cytotoxicity was determined in peritoneal macrophages of BALB/c mouse,
      antiparasitic activity was determined against promastigotes and amastigotes of
      WHOM/00LTB 0016 strain of L. amazonensis. Nitric oxide (NO) production,
      interleukin (IL)-12, IL-10 and TNF-alpha secretion were measured in the
      supernatant of uninfected and infected macrophage cultures. It was observed that
      aryl thiosemicarbazones presented in vitro antiparasitic activity against both
      extracellular and intracellular forms of L. amazonensis. However, unlike
      Amphotericin B, these compounds displayed low cytotoxicity towards host cells. In
      addition to observed antiparasitic activity, compounds exhibited modulatory
      properties in the secretion of cytokines and nitrite content from uninfected
      stimulated and L. amazonensis-infected macrophages. In conclusion, we
      demonstrated the in vitro antiparasitic activity against L. amazonensis for aryl
      thiosemicarbazones, which is possible achieved by Th1 cytokine profile
      modulation. These findings are potential useful for drug development against
      cutaneous leishmaniasis.

PMID- 28433565
TI  - Inhibitory effects of pine nodule extract and its component, SJ-2, on
      acetylcholine-induced catecholamine secretion and synthesis in bovine adrenal
      medullary cells.
AB  - Extract of pine nodules (matsufushi) formed by bark proliferation on the surface
      of trees of Pinus tabulaeformis or Pinus massoniana has been used as an analgesic
      for joint pain, rheumatism, neuralgia, dysmenorrhea and other complaints in
      Chinese traditional medicine. Here we report the effects of matsufushi extract
      and its components on catecholamine secretion and synthesis in cultured bovine
      adrenal medullary cells. We found that matsufushi extract (0.0003-0.005%) and its
      component, SJ-2 (5-hydroxy-3-methoxy-trans-stilbene) (0.3-100 MUM), but not the
      other three, concentration-dependently inhibited catecholamine secretion induced
      by acetylcholine, a physiological secretagogue. Matsufushi extract (0.0003
      0.005%) and SJ-2 (0.3-100 MUM) also inhibited 45Ca2+ influx induced by
      acetylcholine in a concentration-dependent manner, similar to its effect on
      catecholamine secretion. They also suppressed 14C-catecholamine synthesis and
      tyrosine hydroxylase activity induced by acetylcholine. In Xenopus oocytes
      expressing alpha3beta4 nicotinic acetylcholine receptors, matsufushi extract
      (0.00003-0.001%) and SJ-2 (1-100 MUM) directly inhibited the current evoked by
      acetylcholine. The present findings suggest that SJ-2, as well as matsufushi
      extract, inhibits acetylcholine-induced catecholamine secretion and synthesis by
      suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal
      medullary cells.

PMID- 28433566
TI  - beta-Aminoisobutyric acid ameliorates the renal fibrosis in mouse obstructed
      kidneys via inhibition of renal fibroblast activation and fibrosis.
AB  - Renal fibrosis is a hallmark feature of chronic kidney disease, which is
      reflected by proliferation and migration of interstitial fibroblasts and
      extracellular matrix (ECM) accumulation. beta-Aminoisobutyric acid (BAIBA) is
      recently demonstrated to exert a protective role from metabolic diseases.
      However, whether and how BAIBA on fibroblast activation and renal fibrosis
      response to angiotensin II (Ang II) remains largely obscure. Herein, we showed
      that BAIBA significantly depressed the proliferation and migration of NRK-49F
      cells in vitro. Treatment with Ang II remarkably up-regulated the expressions of
      fibronectin (FN), collagen 1 (COL 1), alpha-smooth muscle actin (alpha-SMA),
      interleukin-17 (IL-17) and nicotinamide adenine dinucleotide phosphate oxidase
      (NOX2)-derived reactive oxygen species (ROS) production in cultured NRK-49F
      cells. Pretreatment with BAIBA almost blocked Ang II-induced ECM production and
      IL-17-mediated oxidative stress in NRK-49F cells. BAIBA treatment ameliorates
      fibroblasts activation and renal fibrosis in rat obstructed kidneys involving
      inhibition of Ang II/IL-17/ROS signaling transduction, which may be considered as
      a therapeutic candidate for fibrosis-related diseases.

PMID- 28433567
TI  - PPAR-gamma agonist rosiglitazone reduces autophagy and promotes functional
      recovery in experimental traumaticspinal cord injury.
AB  - BACKGROUND: Secondary damage is often more important in determining the
      functional outcome and provides a practical target for therapeutic intervention.
      Rosiglitazone (ROSG) is a potent PPAR-gamma agonist and has been shown to induce
      neuroprotection in animal models of spinal cord injury (SCI). However, it is
      still unclear whether this PPAR-gamma agonist can mediate neuronal autophagy
      after SCI. METHODS: SCI was induced by application of vascular clips (force of
      24g) to the dura via a four-level T5-T8 laminectomy. The role of the PPAR-gamma
      agonist ROSG on neuronal autophagy induced by SCI was investigated. RESULTS: The
      expression of autophagy-related proteins, including microtubule-associated
      protein 1 light chain 3 type II (LC3-II), beclin-1, and cathepsin D, increased
      significantly after SCI. ROSG downregulated autophagy-related protein expression
      and improved the locomotor function after SCI. GW9662 (a PPAR-gamma inhibitor)
      significantly antagonized the effect of ROSG and abolished the protective effect
      on SCI. CONCLUSIONS: Our results clearly demonstrated that the administration of
      ROSG after SCI reduced autophagy and promoted functional recovery after SCI in
      rats.

PMID- 28433568
TI  - The role of copulatory plugs in the mosquito-parasitic nematode Strelkovimermis
      spiculatus.
AB  - The mosquito-parasitic nematode, Strelkovimermis spiculatus (Mermithidae:
      Nematoda) emerges from hosts and aggregates to form mating clusters characterized
      by intense male-male competition for females. Successful males deposit an
      adhesive copulatory plug over the female vulva after insemination. In choice
      experiments, males strongly preferred virgin females, whereas plugged females
      were ignored. Males made no attempt to displace copulatory plugs deposited by
      previous males. Plugged females repelled males without the need for physical
      contact. The observed chemical repellency was independent of females, since
      excised plugs alone showed the same negative male response. Removal of the plug
      shortly after mating reduced fecundity by 90%, presumably due to spermatids
      leaking from the vulva. The plug as a nutritional gift hypothesis was rejected
      because there was no post-mating reduction in plug size that would have indicated
      absorption. Despite being a male adaption to sperm competition, we conclude that
      the copulatory plug serves the fitness needs of both males and females in
      multiple roles that include paternity preservation, reduced male harassment,
      improved male search for mates, increased fecundity, and sperm retention.

PMID- 28433569
TI  - Vitamin D Binding Protein rs7041 polymorphism and high-residual platelet
      reactivity in patients receiving dual antiplatelet therapy with clopidogrel or
      ticagrelor.
AB  - BACKGROUND: Vitamin D deficiency represents a major health problem in general
      population, especially for its association with cardiovascular disorders and
      thrombotic risk, even in patients on dual antiplatelet therapy (DAPT). Vitamin D
      Binding Protein (VDBP) is the main transporter of vitamin D in the bloodstream
      and genetic polymorphisms of this protein have been shown to account for a
      significant variability of vitamin D levels and its systemic effects. Contrasting
      data have linked the rs7041 T->G substitution with cardiovascular disease.
      However, no study has so far addressed the role of rs7041 polymorphism on
      platelet reactivity in patients on DAPT, that was the aim of the present study.
      METHODS: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) for an
      ACS or elective PCI were scheduled for platelet function assessment at 30-90days
      post-discharge. Platelet function was assessed by Multiplate(r) (Roche
      Diagnostics AG), and VDBP genetic status by polymerase chain reaction and
      restriction fragment length polymorphism technique. Fasting samples were obtained
      for main chemistry parameters and vitamin D levels assessment. RESULTS: We
      included 400 patients, 187 (46.8%) receiving clopidogrel and 213 (53.2%)
      ticagrelor. The genetic polymorphism rs7041 (T->G) was observed in 318 patients,
      (79.5%), in 38.7% of them in homozygosis. Main clinical and chemistry features
      did not significantly differ according to genetic status, but for a higher rate
      of ACE-inhibitors and beta-blockers use among the carriers of the G allele
      (p=0.04 and p=0.01, respectively). VDBP genetic status did not affect the rate of
      HRPR with ADP-antagonists (25.6% vs 24.6% vs 28.5%, p=0.59; adjusted
      OR[95%CI]=0.94[0.52-1.7], p=0.83 for T/G patients; adjusted OR[95%CI]=1.14[0.6
      2.2], p=0.67 for G homozygotes). However, the rate of HRPR with ADP-antagonists
      was influenced by severe hypovitaminosis D (< 10ng/ml) only in patients carrying
      the G allele, especially in homozygosis (T/T: 25.9% vs 26.1%, p=0.99; G carriers:
      22.1% vs 35.3%, p=0.02, pinteraction=0.019; adjusted OR[95%CI]=1.93[1.11-3.34],
      p=0.02 for G carriers). CONCLUSION: The present study shows that rs7041
      polymorphism of Vitamin D Binding Protein does not affect platelet reactivity or
      the rate of HRPR among patients receiving DAPT. However the carriage of the G
      allele could condition the impact of hypovitaminosis D on the response to
      antiplatelet agents, increasing the occurrence of HRPR especially in homozygotes,
      thus suggesting a more significant role of vitamin D deficiency among these
      patients.

PMID- 28433570
TI  - Association Between Environmental Tobacco Smoke Exposure and the Occurrence of
      EGFR Mutations and ALK Rearrangements in Never-smokers With Non-Small-cell Lung
      Cancer: Analyses From a Prospective Multinational ETS Registry.
AB  - BACKGROUND: Molecular studies have demonstrated actionable driver oncogene
      alterations are more frequent in never-smokers with non-small-cell lung cancer
      (NSCLC). The etiology of these driver oncogenes in patients with NSCLC remains
      unknown, and environmental tobacco smoke (ETS) is a potential cause in these
      cases. MATERIALS AND METHODS: We assembled clinical and genetic information for
      never-smoker patients with NSCLC accrued in Japan, Korea, Singapore, and the
      United States. To determine an association between cumulative ETS and activating
      EGFR mutations or ALK rearrangements, the Mantel extension test was used.
      Multivariate analysis on activating EGFR and ALK gene rearrangements was
      performed using the generalized linear mixed model with nations as a random
      effect. RESULTS: From July 2007 to December 2012, 498 never-smokers with
      pathologically proven NSCLC were registered and tested for the association
      between ETS and EGFR and ALK status. EGFR mutations were more frequent in the
      ever-ETS cohort (58.4%) compared with the never-ETS cohort (39.6%), and the
      incidence of EGFR mutations was significantly associated with the increment of
      cumulative ETS (cETS) in female never-smokers (P = .033), whereas the incidence
      of ALK rearrangements was not significantly different between the ever-ETS and
      never-ETS cohorts. Odds ratio for EGFR mutations for each 10-year increment in
      cETS was 1.091 and 0.89 for female and male never-smokers (P = .031 and P = .263,
      respectively). CONCLUSION: Increased ETS exposure was closely associated with
      EGFR mutations in female never-smokers with NSCLC in the expanded multinational
      cohort. However, the association of ETS and ALK rearrangements in never-smokers
      with NSCLC was not significant.

PMID- 28433571
TI  - Antitumor and chemosensitizing action of 3-bromopyruvate: Implication of
      deregulated metabolism.
AB  - 3-Bromopyruvate (3-BP), brominated derivative of pyruvate, possesses strong
      antitumor potential, owing to its ability to inhibit multiple target molecules
      crucial for survival of neoplastic cells. Although, 3-BP displays cytotoxicity
      against a wide variety of tumors, there is no report with respect to malignancies
      of thymic origin. Therefore, we investigated its antineoplastic action in vitro
      against tumor cells of a murine transplantable lymphoma of thymoma origin,
      designated as Dalton's lymphoma (DL). 3-BP treatment of tumor cells inhibited
      metabolism and survival with augmented induction of apoptosis and necrosis. 3-BP
      treatment suppressed lactate release, glucose uptake, deregulated pH homeostasis
      and augmented chemosensitization. It also altered expression of metabolism,
      chemosensitivity and cell survival regulatory molecules including HK 2, GAPDH,
      LDH, SDH, HIF-1alpha, MDR-1 & GLUT-1 and cytokine repertoire of IFN-gamma, IL-6,
      IL-10, & VEGF. Pretreatment with MCT-1 inhibitor alpha-cyano-4-hydroxycinnamate
      and siRNA gene silencing of HK 2 implicated the role of MCT-1 and HK 2 in 3-BP
      cytotoxicity. 3-BP also altered expression of cell death regulatory Bcl-2, Mcl-1,
      caspase-3 accompanied by increased cytochrome c release, indicating mitochondrial
      mode of cell death. The study collates possible molecular mechanisms of cytotoxic
      action of 3-BP, which will help to optimize the therapeutic efficacy of 3-BP
      against tumors of thymic origin.

PMID- 28433572
TI  - Descriptions of the female and larva of Simulium (Gomphostilbia) udomi (Diptera:
      Simuliidae) from Thailand, and its transfer to the Simulium asakoae species
      group.
AB  - The female and larva of Simulium (Gomphostilbia) udomi Takaoka & Choochote from
      Thailand are described for the first time. The female of this species is similar
      to those of S. (G.) asakoae Takaoka & Davies from Peninsular Malaysia, Thailand,
      Hong Kong and Vietnam, and S. (G.) chiangdaoense Takaoka & Srisuka from Thailand.
      The larva of this species is similar to S. (G.) curtatum Jitklang et al. and S.
      (G.) nr. asakoae 2 from Thailand in having a medium-long postgenal cleft.
      Taxonomic notes are given to separate this species from these related species.
      The COI gene sequence of S. (G.) udomi is compared with those of eight species of
      the S. asakoae species-group and three species of the S. ceylonicum species
      group. This species is transferred from the S. ceylonicum species-group to the S.
      asakoae species-group based on the adult female and male morphological
      characters, comparisons of the genetic distances and phylogenetic relationships
      inferred from the COI gene sequences.

PMID- 28433573
TI  - Rodents as a reservoir of infection caused by multiple zoonotic species/genotypes
      of C. parvum, C. hominis, C. suis, C. scrofarum, and the first evidence of C.
      muskrat genotypes I and II of rodents in Europe.
AB  - Cryptosporidium spp. is an important causative agent of intestinal parasitoses
      induced diarrhoea in humans and animals worldwide. Rodents (small mammals), the
      main reservoir of infections, are globally expanded and overpopulated, which
      increases the risk of transfer of human and zoonotic pathogens from the genus
      Cryptosporidium. In this study, Cryptosporidium was detected in wild
      immunocompetent asymptomatic small mammals. Altogether 262 fecal samples were
      collected from five areas in Eastern Slovakia from four different rodent species
      (Myodes glareolus, Apodemus agrarius, Apodemus flavicollis, Rattus norvegicus),
      eight samples originated from two insectivore species (Sorex araneus, Crocidura
      suaveolens), and two sample from a carnivore Mustela nivalis. The samples were
      examined using a method modified in our laboratory, based on the use of specific
      primers on a small subunit rRNA (18S rRNA) gene for species identification, and
      amplification of GP60 gene coding 60-kDa glycoprotein for genotype determination.
      The following species were identified: Cryptosporidium parvum (n=15), genotypes
      IIaA18G3R1 (n=11; KU311673), IIaA10G1R1 (n=1; KU311670), IIcA5G3a (n=1;
      KU311669), IIiA10 (n=2; KU311672); Cryptosporidium suis (n=4; KU311671);
      Cryptosporidium scrofarum (n=28); Cryptosporidium environment sp. (n=12;
      KU311677); Cryptosporidium muskrat genotype I (n=3; KU311675); Cryptosporidium
      muskrat genotype II (n=3; KU311676). From one of the rodent, the species
      Cryptosporidium hominis genotype IbA10G2 (KU311668) was identified for the first
      time. The results of this study indicate low host specificity of the detected
      Cryptosporidium species and imply the importance of free-living small mammals in
      urban and suburban habitats as a potential source of human cryptosporidiosis.

PMID- 28433575
TI  - Skeletal myositis as the sole feature of relapsing drug reaction with
      eosinophilia and systemic symptoms syndrome.

PMID- 28433574
TI  - Serodiagnosis of Toxoplasmosis: The effect of measurement of IgG avidity in
      pregnant women in Rabat in Morocco.
AB  - BACKGROUND: The diagnosis of Toxoplasmosis in pregnant women during the early
      first trimester of pregnancy is very important for preventing congenital
      infection of the fetus; it will not only prevent the risk of transmitting the
      infection to the fetus but it will also enable to give these women a preventive
      treatment. In this study, the avidity test was performed on pregnant women during
      their first prenatal visit at the National Institute of Hygiene in Rabat,
      Morocco. FINDINGS: One hundred and twenty-eight sera samples were collected from
      128 pregnant women between August 2015 and June 2016; these women were chosen
      retrospectively and were in their first four months of pregnancy. The samples
      were screened using the specific anti-Toxoplasma IgG and IgM antibodies and were
      subjected to an IgG avidity test. After the serological screening, only 54 women
      (42.4%) were tested positive for IgG antibodies and five women (3.9%) were tested
      positive for both anti-Toxoplasma IgG and IgM antibodies. Four IgM-negative women
      had low-avidity antibodies. However, none of the IgG-avidity test had detected
      low-avidity antibodies in the five IgM-positive women; three women (60%) had high
      avidity antibodies, indicating that the infection was acquired in the distant
      past. CONCLUSION: The avidity test is a helpful tool to exclude a recently
      acquired toxoplasmosis infection within IgM-positive serum samples in pregnant
      women during their first trimester of pregnancy. Thus, allowing to perform an
      appropriate therapeutic intervention.

PMID- 28433576
TI  - Proptosis and vision loss as grave complications of allergic fungal sinusitis and
      polyposis.

PMID- 28433577
TI  - Asthma and risk of coronary heart disease: A meta-analysis of cohort studies.
AB  - BACKGROUND: Few studies have investigated the incidence of coronary heart disease
      (CHD) in patients with asthma, and their results remain inconclusive. OBJECTIVE:
      To conduct a meta-analysis to determine whether asthma increases the risk of CHD.
      METHODS: A systematic literature search of the PubMed and Embase databases from
      inception to August 2016, complemented with references screening of relevant
      articles and reviews, was performed to identify eligible studies. Only
      longitudinal cohort studies were included in our meta-analysis. RESULTS: The
      retrieval process yielded 7 studies (12 asthma cohorts) with 495,024 patients.
      Data pooling across the cohorts revealed that asthma was associated with an
      increased risk of CHD (hazard ratio [HR], 1.42; 95% confidence interval [CI],
      1.30-1.57; P < .001), without significant heterogeneity across the studies (I2 =
      26%, P = .19). This epidemiologic association was more pronounced in female than
      in male patients (female: HR, 1.50; 95% CI, 1.41-1.59; male: HR, 1.31; 95% CI,
      1.16-1.47; P for interaction = .046). In addition, subgroup and sensitivity
      analyses supported the positive correlation between asthma and incident CHD.
      CONCLUSION: Asthma is related to an increased incidence of CHD, particularly in
      women. Clinicians should be aware of this association when faced with a patient
      with asthma. Further investigations are required to examine how this excess risk
      should be managed in routine practice.

PMID- 28433578
TI  - A novel device for continuous long-term electroencephalogram recording and drug
      administration in mice with a nice, powerful and sophisticated wired system.
AB  - BACKGROUND: To elucidate mechanisms of epileptogenesis and epileptic maturation,
      and to develop new AEDs, it is indispensable to administer various drugs and to
      examine their effects on EEG over a long period of observation. NEW METHOD: We
      constructed a device for the continuous measurement of electroencephalography
      (EEG) and the infusion of anti-epileptic drugs over a prolonged period of time in
      moving mice. The system includes a slip ring and a swivel to prevent twisting of
      the recording cable and infusion tube, respectively. We introduced three arms,
      ball bearing, and stabilizing frame to rotate the slip ring and swivel with only
      a small applied force, and to facilitate the start of rotation of the slip ring
      and the swivel. RESULTS: Continuous EEG recording was successfully performed for
      up to 63 days in 99 mice, for a total of 1872 days of EEG data. Continuous drug
      infusion with continuous EEG recording was successfully performed for up to 22
      days. COMPARISON WITH EXISTING METHOD(S): Our system is superior to current
      system in continuous drug delivery during long-term EEG recording in moving
      mouse. CONCLUSIONS: Our device will be quite useful for long-term EEG recording
      and drug application in moving mice.

PMID- 28433579
TI  - Distinguishing septic from normal donors by detection of sPLA2-IIA from human
      plasma using a microsieve-based immunoassay.
AB  - Bloodstream infections that progress to septic shock are responsible for hundreds
      of thousands of deaths each year, and are associated with significant healthcare
      costs. Recent studies have shown that a member of the secreted phospholipase
      protein family, termed sPLA2-IIA, may play a role during the innate immune
      response to bacterial infections, and is elevated in the plasma of septic
      patients. In this report, the feasibility of a simple microsieve-based sPLA2-IIA
      detection immunoassay was explored. Microsieves containing 5MUm pores were
      covalently coupled with a sPLA2-IIA-specific monoclonal antibody at 0.1, 1.0, and
      10MUg/mL and then assayed with plasma-based positive and negative controls to
      determine the optimal coating concentration. Recombinant sPLA2-IIA was then
      serially diluted to a final concentration of 200, 100, 50, 25, 12.5, and
      6.25ng/mL and tested alongside a non-spiked sample to estimate the detection
      limit of the prototype assay. Recombinant sPLA2-IIA was also spiked into serum,
      EDTA-plasma, and Lithium-Heparin plasma, in an effort to evaluate assay
      performance when analyzing these sample matrices. The preliminary limit of
      detection studies suggests that the microsieve assay is able to distinguish
      approximately 6-12ng/mL of sPLA2-IIA from a non-spiked sample. When compared to
      an immunoassay diluent, the microsieve assay also yielded acceptable percent
      recoveries for each of the three sample matrices spiked with clinically
      significant levels of sPLA2-IIA. The sPLA2-IIA microsieve assay prototype also
      clearly distinguished five samples from septic patients from five normal donor
      samples, and the results were in good agreement with a comparator ELISA test
      system (R2=0.9347).

PMID- 28433580
TI  - Description of a novel multiplex avidity assay for evaluating HPV antibodies.
AB  - Limited data exists regarding antibody avidity for human papillomavirus (HPV). We
      describe development of a multiplex electrochemiluminescent avidity ELISA for
      four HPV types (HPV 6, 11, 16, 18) by adding a dissociating step to our
      established multiplex HPV VLP ELISA. Initial experiments exploring ammonium
      thiocyanate, sodium thiocyanate and guanidine hydrochloride (GuHCl) as
      dissociating agents identified GuHCl as most promising. Dissociation conditions
      with GuHCl were varied (concentration, incubation time, temperature) to select
      conditions with minimal impact on VLP integrity as measured with monoclonal
      antibodies to conformational epitopes. Avidity index (AI) was calculated based on
      a standard curve as ratio of bound IgG in GuHCl treated versus untreated sample.
      To evaluate our assay we determined AI in sera with known HPV titers. We selected
      32 residual anonymized sera from individuals with a wide range of titers for
      HPV6, 11, 16, and 18. AIs were similar across multiple dilutions of serum within
      the assay's dynamic range and were reproducible with two plate lots. This assay
      will aid in understanding HPV antibody avidity and maturation in response to
      natural infection and varying vaccine schedules. This is the first report of a
      VLP-based multiplexed avidity ELISA that evaluates assay parameters for all nine
      HPV vaccine types.

PMID- 28433581
TI  - Therapeutic burst-suppression coma in pediatric febrile refractory status
      epilepticus.
AB  - BACKGROUND: Evidence for the beneficial effect of therapeutic burst-suppression
      coma in pediatric patients with febrile refractory status epilepticus is limited,
      and the clinical outcomes of this treatment strategy are largely unknown.
      Therefore, the aim of this study was to explore the outcomes of therapeutic burst
      suppression coma in a series of children with febrile refractory status
      epilepticus. METHODS: We retrospectively reviewed consecutive pediatric patients
      with febrile refractory status epilepticus admitted to our pediatric intensive
      care unit between January 2000 and December 2013. The clinical characteristics
      were analyzed. RESULTS: Thirty-five patients (23 boys; age range: 1-18years) were
      enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of
      the patients received the continuous administration of intravenous antiepileptic
      drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved
      therapeutic burst-suppression coma. All of the patients received mechanical
      ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%)
      patients died within 1month. The neurologically functional outcomes at 6months
      were good in six (27.3%) of the 22 survivors, of whom two returned to clinical
      baseline. The patients with therapeutic burst-suppression coma were significantly
      associated with hemodynamic support than the patients with electrographic
      seizures control (p=0.03), and had a trend of higher 1-month mortality rate,
      worse 6months outcomes, and a longer duration of hospitalization. CONCLUSIONS:
      Our results suggest that therapeutic burst-suppression coma to treat febrile
      refractory status epilepticus may lead to an increased risk of hemodynamic
      instability and a trend of worse outcomes.

PMID- 28433582
TI  - Effects of twenty standard amino acids on biochemical constituents,
      docosahexaenoic acid production and metabolic activity changes of Crypthecodinium
      cohnii.
AB  - The influence of 20 standard amino acids was investigated on growth, lipid
      accumulation, docosahexaenoic acid (DHA) production and cell biochemical
      composition of Crypthecodinium cohnii. C. cohnii efficiently utilize organic
      nitrogen (predominantly threonine and to a lesser extent tyrosine and serine) as
      compared to inorganic nitrogen (NH4)2SO4. However, No significant effect was
      observed on major biochemical composition of C. cohnii (lipids, carbohydrates and
      proteins) under N limitation or supplementation with different N-sources. Key
      lipogenic enzymes glucose-6-phosphate dehydrogenase, ATP-citrate lyase, fatty
      acid synthase, malic enzyme, citrate synthase (CS), NAD+ and NADP+ dependent
      isocitrate dehydrogenase were shown to be vital in lipogenesis of C. cohnii. Our
      results indicated that the process of lipid accumulation in C. cohnii is growth
      associated and does not depend upon the trigger of nitrogen depletion. This
      unusual behavior would suggest that the metabolism of the cells may not be
      entirely the same as in other lipid-accumulating microorganisms.

PMID- 28433583
TI  - Effect of the reaction medium on the immobilization of nutrients in hydrochars
      obtained using sugarcane industry residues.
AB  - In this study, nutrients were immobilized on the hydrochars obtained by
      hydrothermal carbonization (HTC) of a vinasse and sugarcane bagasse mixture, in
      the presence of acid, base and salt additives at temperatures of 150, 190 and 230
      degrees C. The increase in temperature caused higher immobilization of Ca, Mg, K,
      N, Cu, Mn, Zn, B, P and Fe in all hydrochars produced. H3PO4 and NaOH immobilized
      higher amounts of P, Mg and Mn, while Ca was immobilized in higher quantities in
      the presence of H3PO4 and (NH4)2SO4. The addition of H2SO4, H3PO4 and (NH4)2SO4
      was responsible for an increased immobilization of P, N, Ca, Mg and K. The
      immobilization of B, not present in the starting raw material, was possible with
      the addition of H3BO3. The results showed that it is possible to alter the
      reaction medium to immobilize nutrients on hydrochars produced from vinasse and
      sugarcane bagasse, for agricultural applications.

PMID- 28433584
TI  - Electrohydrolysis pretreatment of water hyacinth for enhanced hydrolysis.
AB  - This study investigates the use of electrohydrolysis pretreatment on water
      hyacinth to cut short the hydrolysis step and increase biogas production at the
      same time. Electrohydrolysis pretreatment of water hyacinth at 20V for 60min
      exhibited improved solubilisation (42.9%). Therefore, bio-chemical methane
      potential (BMP) test was carried out between water hyacinth pretreated at 20V for
      60min and untreated water hyacinth. By the end of 30days, cumulative methane
      production of 2455+/-17mL CH4/g VS for electrohydrolysis pretreated substrate and
      1936+/-27mL CH4/g VS for the untreated substrate was achieved. Compositional
      analysis and characterization study revealed the efficiency of electrohydrolysis
      pretreatment in melting the lignin and lowering the cellulose crystallinity of
      water hyacinth.

PMID- 28433585
TI  - Scale-up for esters production from straw whiskers for biofuel applications.
AB  - Delignified wheat straw was fermented by a mixed bacterial anaerobic culture
      obtained from a UASB reactor to produce organic acids (OAs). Kissiris was used as
      immobilization carrier in a 2-compartment 82L bioreactor filled with 17L of
      fermentation broth for the first 7 fermentation batches and up to 40L for the
      subsequent batches. The amount of straw used was 30g/L and the temperature was
      set at 37 degrees C for all experiments. The total OAs reached concentrations up
      to 17.53g/L and the produced ethanol ranged from 0.3 to 1mL/L. The main OAs
      produced was acetic acid (6-8g/L) and butyric acid (3-8g/L). The OAs were
      recovered from the fermentation broth by a downstream process using 1-butanol,
      which was the solvent with the best recovery yields and also served as the
      esterification alcohol. The enzymatic esterification of OAs resulted to 90%
      yield.

PMID- 28433586
TI  - A comparison of hepatic steatosis index, controlled attenuation parameter and
      ultrasound as noninvasive diagnostic tools for steatosis in chronic hepatitis B.
AB  - AIMS: To evaluate the value of noninvasive tools for diagnosis of hepatic
      steatosis in patients with chronic hepatitis B (CHB). METHODS: Consecutive
      treatment-naive patients with CHB with body mass index less than 30kg/m2 who
      underwent liver biopsy, ultrasound and FibroScan(r) were enrolled. The diagnostic
      performance of controlled attenuation parameter (CAP), hepatic steatosis index
      (HSI) and ultrasound for hepatic steatosis compared with liver biopsy was
      assessed. The areas under receiver operating characteristics curves (AUROCs) were
      calculated to determine the diagnostic efficacy, with comparisons using the
      DeLong test. RESULTS: CAP and HSI accuracies were significantly higher than that
      of ultrasound to detect patients with biopsy-proven mild steatosis (S1, 65.3%,
      56.5%, respectively, vs. 17.7%, chi2=46.305, 31.736, both P<0.05)and moderate
      severe (S2-3) steatosis (92.3%, 100%, respectively, vs. 53.8%, chi2=4.887, 7.800,
      P=0.037, 0.007, respectively). Both CAP and HSI had lower underestimation rates
      of steatosis grade than ultrasound (12%, 14.8%, respectively, vs. 29.5%,
      chi2=9.765, 6.452; P<0.05 for both), but they exhibited higher overestimation
      rates (30.5%, 38.2%, respectively, vs. 12.4%, chi2=39.222, 70.986; both P<0.05).
      The AUROCs of CAP and HSI were 0.780 (95% confidence intervals [CIs] 0.735-0.822)
      and 0.655 (95%CI 0.604-0.704) for S >=1, 0.932 (95%CI 0.902-0.956) and 0.755
      (95%CI 0.707-0.799) for S >=2, 0.990 (95%CI 0.974-0.998) and 0.786 (95% CI 0.740
      0.827) for S3, respectively. CONCLUSION: CAP might be more accurate for detecting
      hepatic steatosis than HSI and ultrasound in patients with CHB, but further
      studies are needed to reduce the overestimation rates.

PMID- 28433587
TI  - Pharmacokinetic and toxicology comparator testing of biosimilar drugs - Assessing
      need.
AB  - A key element in the development of a biosimilar molecule is the comparability of
      the biological activity/nonclinical similarity to the innovator drug. Although
      some regulatory guidelines are encouraging little or no in vivo testing,
      currently a common practice is to perform at least one toxicology and/or one
      pharmacokinetic (PK) study to assess if any different findings occur for in-life,
      clinical pathology and histopathological parameters or in exposure. An exercise
      was performed in which the results of such testing were evaluated. It was found
      that 10 PK comparison studies in the cynomolgus monkey across 4 monoclonal (Mab)
      classes showed similar exposure in all cases. In 17 toxicology comparison studies
      with 5 Mab classes performed in the same species and in 7 toxicology comparison
      studies with non-Mab biosimilars in the rat, no new/unexpected findings were seen
      and drug exposure measurement gave comparable values in all cases. Overall,
      although this work does not rule out possible utility of some in vivo testing
      (notably in the form of stand-alone PK testing) to confirm similar exposure
      between the 2 molecules tested, it is unclear what benefit can be gained from
      toxicology testing, especially if comparability has been demonstrated from
      physiochemical and in vitro characterisation.

PMID- 28433588
TI  - How environmental noise can contract and destroy a persistence zone in population
      models with Allee effect.
AB  - A problem of the analysis of the noise-induced extinction in population models
      with Allee effect is considered. To clarify mechanisms of the extinction, we
      suggest a new technique combining an analysis of the geometry of attractors and
      their stochastic sensitivity. For the conceptual one-dimensional discrete Ricker
      type model, on the base of the bifurcation analysis, deterministic persistence
      zones are constructed in the space of initial states and biological parameters.
      It is shown that the random environmental noise can contract, and even destroy
      these persistence zones. A parametric analysis of the probabilistic mechanism of
      the noise-induced extinction in regular and chaotic zones is carried out with the
      help of the unified approach based on the sensitivity functions technique and
      confidence domains method.

PMID- 28433589
TI  - Low dose out-of-field radiotherapy, part 1: Measurement of scattered doses.
AB  - PURPOSE: To measure out-of-field doses in a phantom model to better quantify this
      radiation. MATERIAL AND METHODS: The individual contribution of photons and
      neutrons to the total out-of-field dose for 6 MV and 20 MV photons at open beam
      were measured in a purpose-designed water phantom. Radiation doses were measured
      at seven separate points (P1-P7) in the phantom with thermoluminescent detectors
      (TLD 100, 600, and 700) and GAFchromicTM EBT films. RESULTS: At a prescribed dose
      of 75Gy to the isocentre, the photon dose level in the close-to-field area (P2)
      ranged from 2.0-2.5Gy for 6 MV and 1.5-2.0Gy for 20 MV; the total out-of-field
      doses at P2 and P7, respectively, were estimated to be as follows: for 6 MV: TLD
      100 (<3.23% and<0.14%); radiochromic film (<2.52% and <0.03%); and for 20 MV: TLD
      100 (<2.94% and <0.78%); TLD 700 (<2.02% and <0.14%); and radiochromic film
      (<1.73% and <0.01%). Although the dose decreased rapidly as the distance from the
      central beam axis increased, even distant doses could be as high as several
      centigrays. The neutron dose for 20 MV photons at a distance of 25cm from the
      isocentre was 4.0mSv/Gy. CONCLUSION: Our results show that in the close-to-field
      area, the dose level could be as high as 1.5Gy assuming a prescribed dose of 75Gy
      to the isocentre. By contrast, the doses delivered to more distant areas from the
      planning target volume were much lower (centigrays). These findings show that
      both 6 MV and 20 MV photons could produce dosimetrically important dose levels
      outside of the field. The data reported here may be of value to study the
      potential impact of even very low doses of radiation on human tissues.

PMID- 28433590
TI  - Low dose out-of-field radiotherapy, part 3: Qualitative and quantitative impact
      of scattered out-of-field radiation on MDA-MB-231 cell lines.
AB  - PURPOSE: Patients who undergo external beam radiotherapy are at risk of
      developing second tumours due to scattered radiation outside the path of the
      primary beam. The aim of this study was to experimentally determine the in vitro
      radiobiological effects of scattered radiation in cells located outside the
      primary photon beam and to compare this to the effects that occur in cells inside
      the primary beam. The comparison was performed by assessing cell viability, DNA
      damage, and apoptosis. MATERIAL AND METHODS: Cells from the human breast cancer
      line MDA-MB-231 were inserted in a water phantom and irradiated at varying doses
      (1.5, 2.0, 2.5, and 3.0Gy). The cells were placed at two geometrical points: in
      the central beam axis and at 10cm out-of-field. The dose was constant in both
      geometrical points. Survival fraction, number of DNA double strand-breaks, and
      cleaved poly-(ADP-ribose) polymerase (PARP) levels were determined by clonogenic
      assay and flow cytometry. RESULTS: A slight, non-significant decrease of 3 to 5%
      in cell survival fraction was observed in cells irradiated outside the primary
      field. The number of PARP-positive cells and DNA double strand-breaks both
      increased after out-of-field irradiation. CONCLUSION: Scattered irradiation
      appears to induce an in vitro biological response on out-of-field cells that is
      stronger than the effect of primary radiation on in-field cells, independent of
      the bystander effect. These findings suggest that the biological response of
      healthy tissues outside the primary beam might be higher than previously
      believed.

PMID- 28433591
TI  - [Artificial intelligence applied to radiation oncology].
AB  - Performing randomised comparative clinical trials in radiation oncology remains a
      challenge when new treatment modalities become available. One of the most recent
      examples is the lack of phase III trials demonstrating the superiority of
      intensity-modulated radiation therapy in most of its current indications. A new
      paradigm is developing that consists in the mining of large databases to answer
      clinical or translational issues. Beyond national databases (such as SEER or
      NCDB), that often lack the necessary level of details on the population studied
      or the treatments performed, electronic health records can be used to create
      detailed phenotypic profiles of any patients. In parallel, the Record-and-Verify
      Systems used in radiation oncology precisely document the planned and performed
      treatments. Artificial Intelligence and machine learning algorithms can be used
      to incrementally analyse these data in order to generate hypothesis to better
      personalize treatments. This review discusses how these methods have already been
      used in previous studies.

PMID- 28433592
TI  - Toxicity assessment of multi-walled carbon nanotubes on Cucurbita pepo L. under
      well-watered and water-stressed conditions.
AB  - The rapid increase in the production and application of various types of
      nanomaterials increases the possibility of their presence in total environment,
      which subsequently raises concerns about their potential threats to the first
      trophic level of organisms, specifically under varying environmental constraints.
      In this work, seeds of Cucurbita pepo L. were cultured in MS basal medium exposed
      to multi-walled carbon nanotubes (MWCNTs) at different concentrations (0, 125,
      250, 500 and 1000MUgmL-1) under two levels of water potential, well-watered
      (0MPa) and water stress (-1.5MPa) induced by polyethylene glycol (PEG 6000) for
      14 days. Seeds exposed to MWCNTs showed reduction in germination percentage, root
      and shoot length, biomass accumulation and vigor index in a dose-dependent
      manner. However, seedlings germinated in MWCNTs-fortified media had significantly
      lower germination and growth attributes than those of control under water stress
      conditions. This happened due to increased oxidative injury indices including
      hydrogen peroxide (H2O2), and malondialdehyde (MDA) contents, as well as
      electrolyte leakage index (ELI) of tissues. The impaired morpho-physiological and
      biochemical processes of seedlings exposed to different concentrations of MWCNTs
      under both PEG-induced stress and non-stress growing conditions were consequence
      of changes in the activation of various cellular antioxidant enzymes such as
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (POD).
      Taken together, our findings reveal that MWCNTs played negative role on seed
      germination and subsequent growth of C. pepo L. seedlings under both levels of
      water potential.

PMID- 28433593
TI  - Tissue distribution and metabolism of triadimefon and triadimenol enantiomers in
      Chinese lizards (Eremias argus).
AB  - Triadimefon (TF, S-(+)-TF, R-(-)-TF) and its metabolite triadimenol (TN, TN-A1,
      A2 and TN-B1, B2) are two systemic fungicides and both of them are chiral
      pharmaceuticals which are widely used in agricultural industry. Many researches
      focused on the toxicity effects of triadimefon on mammals, while the
      ecotoxicological data of tiradimefon on reptiles is limited. In order to
      understand the toxicity mechanism of triadimefon in reptiles, the current study
      administrated S-(+)-TF or R-(-)-TF traidimefon (50mg/kgbw) to Chinese lizards
      (Eremias argus) respectively, the absorption, distribution of triadimefon and the
      formation of triadimenol were analysed at different sampling times. The metabolic
      pathways were demonstrated through relative gene expression using quantitative
      real-time PCR reaction. During the experiment time, triadimefon was quickly
      peaked to the maximum concentration within 12h in liver, brain, kidney, and
      plasma, eliminated slowly. The biotransformation in kidney was the lowest and fat
      possessed the worst degradation ability among others. The metabolite, triadimenol
      was detected in blood in 2h and reached to a plateau at about 12h in most organs
      (fat excepted), while the process of metabolism is stereoselective. The mainly
      metabolite in R-(-)-TF treated group was TN-B1, and TN-A2 in S-(+)-TF group which
      showed the selective metabolism to other species caused by environmental
      conditions, differences in the animal models and concentration of TF. The related
      gene expression of cyp1a1, cyp3a1 and hsd11beta mRNA level in lizards showed
      different metabolic pathways in the liver and brain. Both P450s enzymes and
      11beta-hydroxysteroid dehydrogenase participated in metabolic reaction in liver,
      while no 11beta-hydroxysteroid dehydrogenase pathway observed in brain. This
      diversity in liver and brain may cause different degradation rate and
      ecotoxicological effect in different organs.

PMID- 28433595
TI  - Effects of chlorpyrifos on soil carboxylesterase activity at an aggregate-size
      scale.
AB  - The impact of pesticides on extracellular enzyme activity has been mostly studied
      on the bulk soil scale, and our understanding of the impact on an aggregate-size
      scale remains limited. Because microbial processes, and their extracellular
      enzyme production, are dependent on the size of soil aggregates, we hypothesized
      that the effect of pesticides on enzyme activities is aggregate-size specific. We
      performed three experiments using an Andisol to test the interaction between
      carboxylesterase (CbE) activity and the organophosphorus (OP) chlorpyrifos.
      First, we compared esterase activity among aggregates of different size spiked
      with chlorpyrifos (10mgkg-1 wet soil). Next, we examined the inhibition of CbE
      activity by chlorpyrifos and its metabolite chlorpyrifos-oxon in vitro to explore
      the aggregate size-dependent affinity of the pesticides for the active site of
      the enzyme. Lastly, we assessed the capability of CbEs to alleviate chlorpyrifos
      toxicity upon soil microorganisms. Our principal findings were: 1) CbE activity
      was significantly inhibited (30-67% of controls) in the microaggregates (<0.25mm
      size) and smallest macroaggregates (<1.0 - 0.25mm), but did not change in the
      largest macroaggregates (>1.0mm) compared with the corresponding controls (i.e.,
      pesticide-free aggregates), 2) chlorpyrifos-oxon was a more potent CbE inhibitor
      than chlorpyrifos; however, no significant differences in the CbE inhibition were
      found between micro- and macroaggregates, and 3) dose-response relationships
      between CbE activity and chlorpyrifos concentrations revealed the capability of
      the enzyme to bind chlorpyrifos-oxon, which was dependent on the time of
      exposure. This chemical interaction resulted in a safeguarding mechanism against
      chlorpyrifos-oxon toxicity on soil microbial activity, as evidenced by the
      unchanged activity of dehydrogenase and related extracellular enzymes in the
      pesticide-treated aggregates. Taken together, these results suggest that
      environmental risk assessments of OP-polluted soils should consider the
      fractionation of soil in aggregates of different size to measure the CbE
      activity, and other potential soil enzyme activities.

PMID- 28433594
TI  - Favouring NO over H2O2 production will increase Pb tolerance in Prosopis farcta
      via altered primary metabolism.
AB  - Reactive oxygen species (ROS) and nitric oxide (NO) are known in triggering
      defense functions to detoxify heavy metal stresses. To investigate the relevance
      of ROS production, Pb treatment (400uM) alone and in combination with 400uM
      sodium ascorbate (Asc: as H2O2 scavenger) were given to hydroponically grown
      Prosopis farcta seedlings over a time course of 72h. Data presented here indicate
      that, the low extent of H2O2 due to scavenging by ascorbate, together with high
      level of NO improved Pb+Asc- treated Prosopis growth. Following the evoked
      potential of both the signals, significant increases in phenolic acids; caffeic,
      ferulic and salicylic acid were observed with Pb treatment; which are consistent
      with observed increase in lignin content and consequently with growth inhibition.
      In contrast, Pb+Asc treatment induced more flavonoids (quercetin, kaempferol,
      luteolin), diminished phenolic acids contents and also lignin. Elicited
      expression rate of phenylalanine ammonia-lyase gene (PAL) and also its enzymatic
      activity verified the induced phenylpropanoid metabolism by Pb and Pb+Asc
      treatments. In comparison with Pb stress, Asc+Pb application induced the high
      expression of arginine decarboxylase gene (ADC), in polyamines biosynthesis
      pathway, and conducted the N flow towards polyamines and gamma-amino butyric acid
      (GABA). Examining the impact on enzyme activities, catalase, and guaiacol
      peroxidase; Pb+Asc reduced activity but this increased ascorbate peroxidase, and
      aconitase activity. Our observations are consistent with conditions favouring NO
      production and reduced H2O2 can improve Pb tolerance via wide-ranging effects on
      a primary metabolic network.

PMID- 28433596
TI  - Effects of diuron and carbofuran and their mixtures on the microalgae
      Raphidocelis subcapitata.
AB  - In aquatic environments, organisms are often exposed to mixtures of several
      pesticides. In this study, the effects of carbofuran and diuron and their
      mixtures on the microalgae Raphidocelis subcapitata were investigated. For this
      purpose, toxicity tests were performed with the single compounds (active
      ingredients and commercial formulations) and their combinations (only active
      ingredients). According to the results, the toxicity of active ingredients and
      their commercial formulations to R. subcapitata was similar. In the single
      exposures, both carbofuran and diuron inhibited significantly the R. subcapitata
      growth and caused physiological (chlorophyll a content) and morphological
      (complexity and cell size) changes in cells, as captured by flow cytometry single
      cell properties. Regarding the mixture toxicity tests, data fitted to both
      reference models, concentration addition (CA) and independent action (IA), and
      evidenced significant deviations. After the CA fitting, dose-ratio dependent
      deviation had the best fit to the data, demonstrating synergism caused mainly by
      diuron and antagonism caused mainly by carbofuran. After fitting the IA model, a
      synergistic deviation represented the best fit for the diuron and carbofuran
      mixtures. In general, the two reference models indicated the occurrence of
      synergism in the mixtures of these compounds, especially when diuron was the
      dominant chemical in the combinations. The increased toxicity caused by the
      mixture of these pesticides could pose a greater environmental risk for
      phytoplankton. Thus, exposure to diuron and carbofuran mixtures must also be
      considered in risk assessments, since the combination of these compounds may
      result in more severe effects on algae population growth than single exposures.

PMID- 28433597
TI  - Prediction of toxicity of zinc and nickel mixtures to Artemia sp. at various
      salinities: From additivity to antagonism.
AB  - Few studies have examined the toxicity of metal mixtures to marine organisms
      exposed to different salinities. The aim of the present study was to investigate
      the acute toxicity of zinc and nickel exposures singly and in combination to
      Artemia sp. under salinities of 10, 17, and 35 psu. The mixture concentrations
      were determined according to individual toxic units (TUs) to follow a fixed ratio
      design. Zinc was more toxic than nickel, and both their individual toxicities
      were higher at lower salinities. These changes in toxicity can be attributed to
      the Biotic Ligand Model (BLM) rather than to metal speciation. To analyze the
      mixture effect, the observed data were compared with the expected mixture effects
      predicted by the concentration addition (CA) model and by deviations for
      synergistic/antagonistic interactions and dose-level and dose-ratio dependencies.
      For a salinity of 35 psu, the mixture had no deviations; therefore, the effects
      were additive. After decreasing the salinity to 17 psu, the toxicity pattern
      changed to antagonism at low concentrations and synergism at higher equivalent
      LC50 levels. For the lowest salinity tested (10 psu), antagonism was observed.
      The speciations of both metals were similar when in a mixture and when isolated,
      and changes in toxicity patterns are more related to the organism's physiology
      than metal speciation. Therefore, besides considering chemical interactions in
      real-world scenarios, where several chemicals can be present, the influence of
      abiotic factors, such as salinity, should also be considered.

PMID- 28433598
TI  - MiR-590-5p, a density-sensitive microRNA, inhibits tumorigenesis by targeting
      YAP1 in colorectal cancer.
AB  - YAP1, a transcription co-activator, mediates the biological functions of the
      Hippo pathway. YAP1 inactivation is involved in cell-cell contact inhibition. In
      various tumors, YAP1 is upregulated through multiple mechanisms, and it functions
      as an oncogene. Here, we provided evidence that YAP1 influenced multiple
      signaling pathways in colorectal cancer (CRC) cells. We reported that miR-590-5p
      directly targets YAP1 and inhibits tumorigenesis in CRC cells both in vitro and
      in vivo xenograft model. We analyzed different cell densities and found that
      increased density caused increased expression of miR-590-5p, and decreased
      expression of its precursors (pri- and pre-miR-590). Increasing cancer cell
      density upregulated the expression of a RNase III endonuclease, DICER1. DICER1
      increased miR-590 biogenesis and inhibited YAP1. In DICER1-defective CRC cells,
      addition of pre-miR-590 did not inhibit YAP1 expression. Analyses of clinical
      data demonstrated that the DICER1-miR-590-5p-YAP1 axis was dysregulated in CRC
      specimens and affected patient survival. Cell-cell contact inhibition is crucial
      to prevent uncontrolled cell proliferation. Identification of this cell density
      sensitive, DICER1-miR-590-5p-YAP1 axis may provide a basis for developing new
      biomarkers or targeted therapies for CRC.

PMID- 28433599
TI  - Coronectomy and dentigerous cysts: a review of 68 patients.
AB  - OBJECTIVE: This large case series retrospectively reviewed the outcomes of
      coronectomy in conjunction with dentigerous cyst removal in 68 patients at the
      oral surgery department of Guy's Hospital. STUDY DESIGN: A retrospective review
      of 68 patients was undertaken in a single department where 73 teeth with
      associated dentigerous cysts were treated by coronectomy to reduce the risk of
      inferior alveolar nerve injury or mandibular fracture. RESULTS: One patient
      experienced permanent injury of the inferior alveolar nerve. There were no
      intraoperative mandibular fractures in this series. Four coronectomy roots
      required retrieval at 2, 4, and 20 months and 10 years after the initial surgery
      due to persistent surgical site infection and incomplete coronectomy with
      retained enamel and associated cystic tissue leading to symptoms. The longest
      follow-up in this series was 10 years for 2 patients, and 30 of 68 patients were
      reviewed between 1 and 3 years postoperatively. CONCLUSION: Coronectomy in
      conjunction with dentigerous cysts is an effective treatment, with minimal
      morbidity seen in both short- and long-term periods.

PMID- 28433600
TI  - Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Metastases of
      Colorectal Cancer: A Multicenter Retrospective Study.
AB  - INTRODUCTION: Hepatic arterial infusion chemotherapy (HAIC) is a treatment used
      for liver metastases (LM) of colorectal cancer (CRC). Because of its technical
      conditions, it has been used in only a few experienced centers in France. Our aim
      was to evaluate its feasibility, efficacy and tolerance in 4 centers. METHODS:
      Clinical, biological, and radiological data of patients treated with HAIC for
      unresectable LM from CRC in 4 institutions from October 2011 to January 2016 were
      retrospectively analyzed. RESULTS: Sixty-one patients with unresectable LM from
      CRC were included. Patients had previously received systemic chemotherapy in 95%
      of patients and 82.8% had previous oxaliplatin treatment. Oxaliplatin was
      administered using an intra-arterial route combined with intravenous (I.V.) Five
      fluorouracil (5-FU) with leucovorin alone in 43.3% of patients, or combined with
      other I.V. chemotherapies or monoclonal antibodies in 56.7% of patients. Grade 3
      to 4 clinical toxicities were reported in 16% of patients, including 9.8% of
      neurotoxicity, and Grade 3 to 4 biological toxicities were reported in 24.6% of
      patients including 22.2% with neutropenia. Catheter-related complications were
      observed in 31.1%. Tumor response rate in first- and second-line was 26.5% and
      third- and fourth-line was 11%. Median overall survival (OS) in first- and second
      line was 13.5 months and third- and fourth-line was 8.3 months (hazard ratio
      [HR], 0.66; 95% confidence interval [CI], 0.39-1.12; P = .1729). Median
      progression-free survival (PFS) in first- and second-line was 9 months and third-
      and fourth-line were 6 months (HR, 0.53; 95% CI, 0.18-0.659; P = .0037). A
      secondary R0 resection was possible in 10 cases (16.4%) allowing a 2-year
      survival of 80%. CONCLUSION: These data confirm that in centers that recently
      developed HAIC using oxaliplatin, this treatment is feasible and has acceptable
      tolerance. The results, in terms of hepatic PFS, PFS, OS, and the rate of
      secondary resections of LM, are in the range of published data, and they confirm
      the interest of HAIC in patients in progression after multiple I.V. TREATMENTS: 

PMID- 28433602
TI  - FOLFOXIRI Regimen for Metastatic Colorectal Cancer: A Systematic Review and Meta
      Analysis.
AB  - INTRODUCTION: Cytotoxic chemotherapy is the mainstay treatment for metastatic
      colorectal cancer (mCRC). Fluoropyrimidines, oxaliplatin, and irinotecan are the
      most active drugs; however, their optimal sequencing has not yet been
      established. Some evidence has shown that upfront treatment with 5-fluorouracil,
      oxaliplatin, and irinotecan (FOLFOXIRI regimen) can improve outcomes for patients
      with mCRC. MATERIALS AND METHODS: We performed a systematic search in electronic
      databases. Studies reporting results from prospective, randomized clinical trials
      comparing FOLFOXIRI to less aggressive regimens for treatment of mCRC were
      selected for meta-analysis. Overall survival (OS), progression-free survival
      (PFS), overall response rate (ORR), and toxicity were the outcomes of interest.
      The pooled hazard ratio (HR) and pooled odds ratio (OR) was calculated for the
      time-to-event endpoints and dichotomous endpoints, respectively. RESULTS: Four
      studies were included in the final analysis. The pooled data showed a significant
      benefit favoring FOLFOXIRI in terms of OS (HR, 0.80; 95% confidence interval
      [CI], 0.70-0.92), PFS (HR, 0.68; 95% CI, 0.55-0.85), and ORR (OR, 1.9; 95% CI,
      1.36-2.67). Toxicity was significantly greater in the FOLFOXIRI arm.
      Heterogeneity across trials and risk of publication bias were low. CONCLUSION:
      FOLFOXIRI provides superior outcomes for mCRC compared with standard chemotherapy
      regimens. The toxicity is greater with FOLFOXIRI but manageable. The role of
      targeted agents combined with FOLFOXIRI is uncertain, and further research is
      warranted.

PMID- 28433601
TI  - Volumetric Versus Unidimensional Measures of Metastatic Colorectal Cancer in
      Assessing Disease Response.
AB  - INTRODUCTION: The purpose of this study was to compare unidimensional (1D/linear)
      and volumetric (3D) measures of metastatic colorectal cancer (mCRC) at computed
      tomography (CT) for predicting clinical outcome. PATIENTS AND METHODS: Analysis
      of CT images in 105 patients (mean age, 59 years; range, 25-81 years; 45 women,
      60 men) receiving treatment for mCRC was performed. Both unidimensional and
      volumetric measures were obtained on index lesions at 3 time points
      (baseline/midpoint/post-therapy; mean interval, 4.1 months; median, 3.7 months)
      by 3 readers using a semi-automated technique. Measurements were summed and
      compared using best overall response across the 3 time points. Patient response
      was categorized based on Response Evaluation Criteria In Solid Tumors (RECIST)
      1.1 thresholds for unidimensional and volume measures (CR, complete response; PR,
      partial response; SD, stable disease; PD, progressive disease). Survival data was
      correlated (mean follow-up, 19.9 +/- 17.1 months; median, 14.7 months).
      Intra/interobserver variability and reproducibility of 1D and 3D measures was
      assessed. Cox survival and Kaplan-Meier models were constructed and compared.
      RESULTS: Cox models and Kaplan-Meier curves for unidimensional versus volumetric
      assessment were very similar in appearance. Both 1D and 3D measurements
      effectively separated PD from the SD/PR groups, but neither separated SD from PR
      well. Volumetric measures showed comparable intra/interobserver variability on
      Bland-Altman analysis to unidimensional measures across readers using a semi
      automated measurement technique. Metastatic site (lung, liver, node, other) did
      not seem to impact measurement reproducibility. CONCLUSIONS: Although CT
      volumetric assessment of metastatic colorectal cancer is fairly reproducible by
      reader and site using a semi-automated technique, the ability to stratify
      progressive disease from other disease response categories in terms of survival
      was similar to unidimensional measurement.

PMID- 28433603
TI  - In Hindsight: What I Wish I Knew Before Becoming a Junior Faculty Member.

PMID- 28433604
TI  - Message From Frank J. Rybicki, MD, Incoming Chair of ACR Appropriateness
      Criteria.

PMID- 28433606
TI  - In silico methods for co-transcriptional RNA secondary structure prediction and
      for investigating alternative RNA structure expression.
AB  - RNA transcripts are the primary products of active genes in any living organism,
      including many viruses. Their cellular destiny not only depends on primary
      sequence signals, but can also be determined by RNA structure. Recent
      experimental evidence shows that many transcripts can be assigned more than a
      single functional RNA structure throughout their cellular life and that structure
      formation happens co-transcriptionally, i.e. as the transcript is synthesised in
      the cell. Moreover, functional RNA structures are not limited to non-coding
      transcripts, but can also feature in coding transcripts. The picture that now
      emerges is that RNA structures constitute an additional layer of information that
      can be encoded in any RNA transcript (and on top of other layers of information
      such as protein-context) in order to exert a wide range of functional roles.
      Moreover, different encoded RNA structures can be expressed at different stages
      of a transcript's life in order to alter the transcript's behaviour depending on
      its actual cellular context. Similar to the concept of alternative splicing for
      protein-coding genes, where a single transcript can yield different proteins
      depending on cellular context, it is thus appropriate to propose the notion of
      alternative RNA structure expression for any given transcript. This review
      introduces several computational strategies that my group developed to detect
      different aspects of RNA structure expression in vivo. Two aspects are of
      particular interest to us: (1) RNA secondary structure features that emerge
      during co-transcriptional folding and (2) functional RNA structure features that
      are expressed at different times of a transcript's life and potentially mutually
      exclusive.

PMID- 28433605
TI  - Stability of patient-specific features of altered DNA replication timing in
      xenografts of primary human acute lymphoblastic leukemia.
AB  - Genome-wide DNA replication timing (RT) profiles reflect the global three
      dimensional chromosome architecture of cells. They also provide a comprehensive
      and unique megabase-scale picture of cellular epigenetic state. Thus, normal
      differentiation involves reproducible changes in RT, and transformation generally
      perturbs these, although the potential effects of altered RT on the properties of
      transformed cells remain largely unknown. A major challenge to interrogating
      these issues in human acute lymphoid leukemia (ALL) is the low proliferative
      activity of most of the cells, which may be further reduced in cryopreserved
      samples and difficult to overcome in vitro. In contrast, the ability of many
      human ALL cell populations to expand when transplanted into highly
      immunodeficient mice is well documented. To examine the stability of DNA RT
      profiles of serially passaged xenografts of primary human B- and T-ALL cells, we
      first devised a method that circumvents the need for bromodeoxyuridine
      incorporation to distinguish early versus late S-phase cells. Using this and more
      standard protocols, we found consistently strong retention in xenografts of the
      original patient-specific RT features. Moreover, in a case in which genomic
      analyses indicated changing subclonal dynamics in serial passages, the RT
      profiles tracked concordantly. These results indicate that DNA RT is a relatively
      stable feature of human ALLs propagated in immunodeficient mice. In addition,
      they suggest the power of this approach for future interrogation of the origin
      and consequences of altered DNA RT in ALL.

PMID- 28433607
TI  - Transfer of vaginal chloramphenicol to circulating blood in pregnant women and
      its relationship with their maternal background and neonatal health.
AB  - Few clinical studies have determined the quantitative transfer of vaginal
      chloramphenicol to circulating blood in pregnant women. This study aimed to
      evaluate the plasma concentration of chloramphenicol in pregnant women treated
      with trans-vaginal tablets and its relationship with maternal background and
      neonatal health. Thirty-seven pregnant women treated with 100 mg of trans-vaginal
      chloramphenicol once daily for bacterial vaginosis and its suspected case were
      enrolled. The plasma concentration of chloramphenicol was determined using liquid
      chromatography coupled to tandem mass spectrometry at day 2 or later after
      starting the medication. The correlations between the maternal plasma
      concentration of chloramphenicol and the background and neonatal health at birth
      were investigated. Chloramphenicol was detected from all maternal plasma
      specimens and its concentration ranged from 0.043 to 73.1 ng/mL. The plasma
      concentration of chloramphenicol declined significantly with the administration
      period. The plasma concentration of chloramphenicol was lower at the second than
      the first blood sampling. No correlations were observed between the maternal
      plasma concentration of chloramphenicol and background such as number of previous
      births, gestational age at dosing, and clinical laboratory data. Neonatal infant
      health parameters such as birth-weight, Apgar score at birth, and gestational age
      at the time of childbearing were not related to the maternal plasma concentration
      of chloramphenicol. Vaginal chloramphenicol transfers to circulating blood in
      pregnant women. The maternal plasma concentration of chloramphenicol varied
      markedly and was associated with the administration day, but not with maternal
      background or her neonatal health.

PMID- 28433608
TI  - Toward biotechnology in space: High-throughput instruments for in situ biological
      research beyond Earth.
AB  - Space biotechnology is a nascent field aimed at applying tools of modern biology
      to advance our goals in space exploration. These advances rely on our ability to
      exploit in situ high throughput techniques for amplification and sequencing DNA,
      and measuring levels of RNA transcripts, proteins and metabolites in a cell.
      These techniques, collectively known as "omics" techniques have already
      revolutionized terrestrial biology. A number of on-going efforts are aimed at
      developing instruments to carry out "omics" research in space, in particular on
      board the International Space Station and small satellites. For space
      applications these instruments require substantial and creative reengineering
      that includes automation, miniaturization and ensuring that the device is
      resistant to conditions in space and works independently of the direction of the
      gravity vector. Different paths taken to meet these requirements for different
      "omics" instruments are the subjects of this review. The advantages and
      disadvantages of these instruments and technological solutions and their level of
      readiness for deployment in space are discussed. Considering that effects of
      space environments on terrestrial organisms appear to be global, it is argued
      that high throughput instruments are essential to advance (1) biomedical and
      physiological studies to control and reduce space-related stressors on living
      systems, (2) application of biology to life support and in situ resource
      utilization, (3) planetary protection, and (4) basic research about the limits on
      life in space. It is also argued that carrying out measurements in situ provides
      considerable advantages over the traditional space biology paradigm that relies
      on post-flight data analysis.

PMID- 28433609
TI  - Hb Moncloa: A new variant of haemoglobin that interferes in the quantification of
      Hb A1c.
AB  - BACKGROUND: In most routine laboratories in Spain, the commonly used method for
      evaluating HbA1c is ion-exchange high performance liquid chromatography (HPLC).
      The presence of a variant of Hb may interfere with the quantification of HbA1c.
      AIMS: Here, we report a novel haemoglobin variant, named Hb Moncloa, which was
      found during a routine health check at the Hospital Clinico San Carlos in Moncloa
      (Madrid), Spain. METHODS AND RESULTS: Molecular characterization of beta gene
      identified a novel transversion mutation [beta80(EF4)Asn>Ser; HBB:c.242A>G].
      CONCLUSIONS: When there is no correlation between clinical, glycemic status and
      glycated haemoglobin of the patient, the chromatogram of HbA1c should be
      carefully checked to detect the possible presence of variants that cause
      interference in their measurement.

PMID- 28433611
TI  - Preanalytical variables for liquid chromatography-mass spectrometry (LC-MS)
      analysis of human blood specimens.
AB  - The use of liquid chromatography-mass spectrometry (LC-MS) for both diagnostics
      and research purposes is rapidly growing in clinical laboratories. As for more
      conventional areas of in vitro diagnostic testing, many preanalytical variables
      have an impact on these techniques and may hence jeopardize the quality of tests
      results. The leading preanalytical variables include patient preparation, the
      nature of the blood collection tubes and additives, interference from spurious
      hemolysis, sample handling and management, composition of blood tubes,
      contamination, as well as storage conditions. Therefore, the aim of this article
      is provide a narrative overview about the leading preanalytical issues which may
      ultimately influence LC-MS testing of human blood samples, and provide tentative
      indications, as for current evidence, about optimal preanalytical management of
      blood samples for proteomics and metabolomics studies. These general
      recommendations entail pre-storage centrifugation, use of appropriate tubes and
      additives, addition of bacteriostatic preservatives, enrichment and purification
      of samples, elimination of unsuitable specimens, rapid analysis or immediate
      storage at -70 degrees C, and avoidance of analyzing frozen-thawed specimens.

PMID- 28433610
TI  - Paraoxonases and infectious diseases.
AB  - The paraoxonases (PON1, PON2 and PON3) are an enzyme family with a high
      structural homology. All of them have lactonase activity and degrade lipid
      peroxides in lipoproteins and cells. As such, they play a role in protection
      against oxidation and inflammation. Infectious diseases are often associated with
      oxidative stress and an inflammatory response. Infection and inflammation trigger
      a cascade of reactions in the host, known as the acute-phase response. This
      response is associated with dramatic changes in serum proteins and lipoproteins,
      including a decrease in serum PON1 activity. These alterations have clinical
      consequences for the infected patient, including an increased risk for
      cardiovascular diseases, and an impaired protection against the formation of
      antibiotic-resistant bacterial biofilms. Several studies have investigated the
      value of serum PON1 measurement as a biomarker of the infection process. Low
      serum PON1 activities are associated with poor survival in patients with severe
      sepsis. In addition, preliminary studies suggest that serum PON1 concentration
      and/or enzyme activity may be useful as markers of acute concomitant infection in
      patients with an indwelling central venous catheter. Investigating the
      associations between paraoxonases and infectious diseases is a recent, and
      productive, line of research.

PMID- 28433612
TI  - Use of enteroscopy for the detection of malignant and premalignant lesions of the
      small bowel in complicated celiac disease: a meta-analysis.
AB  - BACKGROUND AND AIMS: Enteroscopy (wireless or wired) is the reference standard
      for small-bowel (SB) diseases, and it has been applied to detect SB malignancies
      in complicated celiac disease (CD) with heterogeneous results. The aim of this
      meta-analysis was to obtain a diagnostic yield (DY) by pooling the data of
      studies that investigated the use of enteroscopy to detect SB adverse events in
      CD. METHODS: We performed an online search for studies estimating the DY of
      wireless and wired enteroscopy in predicting the presence of SB premalignant
      and/or malignant lesions. The DerSimonian and Laird random-effects method was
      used to pool the arcsine-transformed proportions of patients with the events.
      Three meta-analyses were performed considering the following events: the presence
      of a malignancy, premalignant damage (ulcerative jejunoileitis [UJ]), or the
      presence of a malignancy or UJ. A subgroup analysis was performed after
      extracting (if possible) patients with refractory CD (RCD). RESULTS: Of the 529
      titles initially resulting from the search, 10 studies on capsule enteroscopy
      (CE) and 3 on double-balloon or push enteroscopy met the inclusion criteria.
      Overall, 439 and 76 patients were enrolled in these studies using CE and
      enteroscopy, respectively. Twelve tumors and 47 UJs were found by CE versus 8
      tumors and 13 UJs detected by wired enteroscopy. For malignancies the CE yield
      was 1.9% (95% CI, .5%-3.8%) and wired enteroscopy yield 8.7% (95% CI, 0%-21.2%);
      similarly, for UJ the DYs were 8.4% (95% CI, 2.1%-17.7%) and 16.7% (95% CI, 8.7%
      26.3%); for either UJ or neoplasia the DYs were 13.0% (95% CI, 5.6%-22.5%) and
      27.7% (95% CI, 14.8%-42.6%). For RCD the DYs of all enteroscopic techniques were
      1.8% (95% CI, 0%-7.7%) for neoplasia, 22.3% (95% CI, 8.2%-39.7%) for UJ, and
      27.5% (95% CI, 13.1%-44.2%) for either. CONCLUSIONS: Enteroscopy is a powerful
      and efficient diagnostic tool for the detection of SB malignancies in complicated
      CD.

PMID- 28433613
TI  - Association between early ERCP and mortality in patients with acute cholangitis.
AB  - BACKGROUND AND AIMS: Acute cholangitis (AC) is associated with high mortality of
      up to 10%. The association between timing of ERCP and mortality in patients with
      AC remains unclear. The aim of this study was to investigate whether early ERCP
      within 24 hours was associated with improved survival. METHODS: All patients who
      underwent ERCP at Odense University Hospital, Denmark, between March 2009 and
      September 2016 were identified using a prospective ERCP database. Clinical data
      were collected from medical records. Patients fulfilling the Tokyo Guidelines
      2013 criteria and for whom a detailed review of medical records revealed evidence
      of AC were included. We investigated the association between ERCP within 24 hours
      and 30-day mortality using logistic regression analysis with adjustment for
      confounding factors. RESULTS: A total of 4066 consecutive patients underwent ERCP
      during the study period, and 166 patients fulfilled the inclusion criteria. Forty
      eight patients (29%) underwent ERCP within 24 hours from the time of
      hospitalization, and 118 patients (71%) underwent later ERCP. Patients undergoing
      ERCP within 24 hours were younger (medians: 65 vs 73 years; P = .01) and had a
      higher heart rate (medians: 95 vs 90 beats/minute; P = .02). Overall 30-day
      mortality was 16% (n = 27). Mortality was 8% (n = 4) among patients undergoing
      early ERCP and 19% (n = 23) among patients undergoing later ERCP (P = .10). After
      adjustment for confounding factors, performance of ERCP within 24 hours was
      associated with lower 30-day mortality (odds ratio, 0.23; 95% confidence
      interval, 0.05-0.95; P = .04). CONCLUSION: Our results indicate that early ERCP
      within 24 hours is associated with lower 30-day mortality in patients with AC.

PMID- 28433614
TI  - Association between breast cancer and the risk of colorectal cancer.
AB  - BACKGROUND: The literature to date has suggested a potential increase in
      colorectal cancer (CRC) among patients with breast cancer. METHODS: We performed
      a systematic review of the literature and included 37 retrospective cohort
      studies and 8 case-control studies. The primary aim was to determine the
      prevalence of CRC. Secondary aims included analysis of adenomatous polyps and
      analysis of CRC prevalence by age. We calculated pooled prevalence rates and odds
      ratios (ORs) using random effects models with 95% confidence intervals (CI).
      RESULTS: We identified 1,055,917 individuals with breast cancer among whom 9097
      cases of CRC were detected. The pooled event rate for CRC was 0.7% (95% CI, 0.6%
      0.9%; I2=97%). Four case-control studies reported prevalence of CRC (N=17,873
      patients with breast cancer and 70,366 controls), including 46 cases of CRC in
      the patients with breast cancer, and 272 CRC in the controls (OR, 1.2; 95% CI,
      0.4%-3.7%; P = .7). Six studies reported prevalence of advanced adenomas in
      patients with breast cancer (N=1087) compared with controls (N=1356) with 62
      cases of advanced adenomas in patients compared with 47 in the controls (OR, 1.5;
      95% CI, 0.97-2.2; P = .07). In patients with breast cancer <50 years old (4
      studies, N=64,706), the pooled OR was increased (OR, 2.5; 95% CI, 1.7-3.5; P
      =.001). In 3 studies of women <45 years old (N=92,594), the risk was increased
      (OR, 2.3; 95% CI, 1.7-2.6; P < .001). CONCLUSIONS: Patients with breast cancer
      should not undergo CRC screening at intervals different from the general
      population. In patients with breast cancer <50 years old, CRC screening should be
      considered at age 45 years.

PMID- 28433615
TI  - Digital technology for treating and preventing mental disorders in low-income and
      middle-income countries: a narrative review of the literature.
AB  - Few individuals living with mental disorders around the globe have access to
      mental health care, yet most have access to a mobile phone. Digital technology
      holds promise for improving access to, and quality of, mental health care. We
      reviewed evidence on the use of mobile, online, and other remote technologies for
      treatment and prevention of mental disorders in low-income and middle-income
      countries. Of the 49 studies identified, most were preliminary evaluations of
      feasibility and acceptability. The findings were promising, showing the potential
      effectiveness of online, text-messaging, and telephone support interventions. We
      summarised the evaluations as: technology for supporting clinical care and
      educating health workers, mobile tools for facilitating diagnosis and detection
      of mental disorders, technologies for promoting treatment adherence and
      supporting recovery, online self-help programmes for individuals with mental
      disorders, and programmes for substance misuse prevention and treatment.
      Continued research is needed to rigorously evaluate effectiveness, assess costs,
      and carefully consider potential risks of digital technology interventions for
      mental disorders, while determining how emerging technologies might support the
      scale-up of mental health treatment and prevention efforts across low-resource
      settings.

PMID- 28433616
TI  - Investigating the link between benign prostatic hypertrophy, BMI and type 2
      diabetes mellitus.
AB  - AIMS: To investigate the link between benign prostatic hypertrophy, BMI and type
      2 diabetes mellitus. MATERIALS AND METHODS: This was the retrospective study
      conducted at the urology clinic of NCRHA and SWRHA, in Trinidad. Data was
      obtained from 85 patients with high PSA values (>4.0ng/mL). The data collected
      were age, ethnicity, weight, height, lifestyle and their most recent blood sugar
      levels were recorded. Ultrasound reports of patients diagnosed with BPH were also
      analyzed to gather data on whether their hyperplasia was benign or malignant.
      RESULTS: The majority of the sample population was of Afro-Trinidadian descent
      (41) followed by East Indian descent (26) and then of mixed ethnicity (18).
      Individuals in the sample population with a normal BMI had a mean PSA value of
      23.66ng/mL, while those with a BMI in the overweight range had a mean PSA value
      of 28.1ng/mL, and those with a BMI in the obese range had a mean PSA value of
      18.5ng/mL. There were no statistically significant differences in the mean values
      of PSA levels between diabetics and non-diabetics, between the 3 major ethnic
      groups in our sample population and between the 3 different groupings based on
      BMI ranges. However it was found that the average mean age of patients of East
      Indian descent (62.96+/-2.23) was significantly lower than that of patients of
      African descent (70.15+/-2.02). CONCLUSIONS: This study did not show any
      significant differences in the mean values of PSA levels between diabetics and
      non-diabetics, between the 3 different groupings based on BMI ranges.

PMID- 28433617
TI  - Induced and controlled dietary ketosis as a regulator of obesity and metabolic
      syndrome pathologies.
AB  - A worsening epidemic of diabetes and its precursor, metabolic syndrome (MetS) is
      engulfing America. A healthy individual, with proper glucose regulation has an
      ability to switch between burning fat and carbohydrates. It has been suggested
      that signaling errors within this homeostatic system, characterized by impaired
      switching of substrate oxidation from glucose to fat in response to insulin, can
      contribute to the etiology of metabolic syndrome and occurs before the
      development of type II diabetes. Glucose regulation with restored insulin
      sensitivity facilitated through clinically regulated, benign dietary ketosis
      (BDK), may significantly reduce, regulate and reverse the adverse pathologies
      common to MetS and obesity. The study assessed if prolonged maintenance of
      induced and controlled physiological, dietary ketosis, would reverse pathological
      processes induced by MetS including a reduction in fasting triglycerides, BMI
      (body mass index) and body fat mass (BFM), weight, a significant decrease and/or
      normalization of hemoglobin A1c (HgA1c) and an increase in resting metabolic rate
      (RMR) and blood ketones. A group of 30 adults, previously diagnosed with MetS by
      their primary care physician, were randomly prescribed to one of three groups: a
      sustained ketogenic diet with no exercise, standard American diet (SAD) with no
      exercise or SAD with 3-5 days per week of exercise (30 min.). The results
      demonstrated that the change over time from week 0 to week 10 was significant
      (p=0.001) in the ketogenic group for weight, body fat percentage, BMI, HgA1c and
      ketones. All variables for the ketogenic group out-performed those of the
      exercise and non-exercise groups, with five of the seven demonstrating
      statistical significance.

PMID- 28433619
TI  - Lack of pathogenic mutations in SOS1 gene in phenytoin-induced gingival
      overgrowth patients.
AB  - OBJECTIVE: Gingival overgrowth is a side effect associated with some distinct
      classes of drugs, such as anticonvulsants, immunosuppressants, and calcium
      channel blockers. One of the main drugs associated with gingival overgrowth is
      the antiepileptic phenytoin, which affects gingival tissues by altering
      extracellular matrix metabolism. It has been shown that mutation of human SOS1
      gene is responsible for a rare hereditary gingival fibromatosis type 1, a benign
      gingival overgrowth. The aim of the present study is to evaluate the possible
      contribution of SOS1 mutation to gingival overgrowth-related phenotype. DESIGN:
      We selected and screened for mutations a group of 24 epileptic patients who
      experienced significant gingival overgrowth following phenytoin therapy. Mutation
      scanning was carried out by denaturing high-performance liquid chromatography
      analysis of the entire coding region of the SOS1 gene. Novel identified variants
      were analyzed in-silico by using Alamut Visual mutation interpretation software,
      and comparison with normal control group was done. RESULTS: Mutation scanning of
      the entire coding sequence of SOS1 gene identified seven intronic variants and
      one new exonic substitution (c.138G>A). The seven common intronic variants were
      not considered to be of pathogenic importance. The exonic substitution c.138G>A
      was found to be absent in 100 ethnically matched normal control chromosomes, but
      was not expected to have functional significance based on prediction
      bioinformatics tools. CONCLUSIONS: This study represents the first mutation
      analysis of the SOS1 gene in phenytoin-induced gingival overgrowth epileptic
      patients. Present results suggest that obvious pathogenic mutations in the SOS1
      gene do not represent a common mechanism underlying phenytoin-induced gingival
      overgrowth in epileptic patients; other mechanisms are likely to be involved in
      the pathogenesis of this drug-induced phenotype.

PMID- 28433618
TI  - Evidence-based recommendations for insulin intensification strategies after basal
      insulin in type 2 diabetes.
AB  - Over the time due to progressive nature of diabetes, proactive intensification of
      the existing insulin therapy becomes imminent as it minimizes patients' exposure
      to chronic hypo/hyperglycaemia and reduces weight gain while achieving
      individualized glycaemic targets. This review focuses on the strength of evidence
      behind various options for intensification, primarily the insulins as also the
      GLP-1 analogues. The recommendations presented here are meant to serve as a guide
      for the physician managing type 2 diabetes patients requiring insulin
      intensification upon failing of basal insulin therapy.

PMID- 28433620
TI  - Depressive behavior induced by unpredictable chronic mild stress increases dentin
      hypersensitivity in rats.
AB  - OBJECTIVE: The present study evaluated the nociceptive response induced by dentin
      hypersensitivity after dental erosion in rats that were exhibited to
      unpredictable chronic mild stress (UCMS)-induced depressive-like behavior.
      DESIGN: Adult male rats were subjected to UCMS (depression [D] group) or not (no
      depression [ND] group) for 30days and received either acidic solution to induce
      dental erosion (E) or water (W), thus forming the WND, END, WD, and ED groups.
      After the end of treatment, depressive-like parameters (i.e., sucrose preference
      and immobility in the forced swim test) and dentin hypersensitivity were
      evaluated. Plasma tumor necrosis factor alpha (TNF-alpha) and corticosterone
      levels were measured, and astrocytic glial fibrillary acidic protein (GFAP)
      expression was evaluated in the prefrontal cortex, hippocampus, amygdala, and
      hypothalamus. RESULTS: Administration of the acidic solution potentiated dentin
      hypersensitivity and increased corticosterone levels in the ED group compared
      with the WD group. TNF-alpha levels only increased in the WD group. The ED group
      exhibited an increase in astrocytic GFAP expression in the hypothalamus and
      prefrontal cortex but decreases in the hippocampus. CONCLUSIONS: These results
      suggest that UCMS exacerbated the nociceptive response associated with dentin
      hypersensitivity, concomitant with an increase in plasma corticosterone levels.
      Hypothalamic and prefrontal cortex astrogliosis in the ED group may be
      attributable to the increase in corticosterone associated to UCMS procedure. The
      reduction of astrocytic GFAP expression in the hippocampus in the ED group
      supports the association between dentin hypersensitivity and depression.

PMID- 28433621
TI  - Simultaneous speciation in the European high mountain flowering plant genus
      Facchinia (Minuartia s.l., Caryophyllaceae) revealed by genotyping-by-sequencing.
AB  - Understanding the relative importance of different mechanisms of speciation in a
      given lineage requires fully resolved interspecific relationships. Using
      Facchinia, a genus of seven species centred in the European Alps, we explore
      whether the polytomy found by Sanger sequencing analyses of standard nuclear
      (ITS) and plastid markers (trnQ-rps16) is a hard or soft polytomy by
      substantially increasing the amount of DNA sequence data, generated by genotyping
      by-sequencing. In comparison to 142 phylogenetically informative sites in the
      Sanger sequences the GBS sequences yielded 3363 phylogenetically informative
      sites after exclusion of apparently oversaturated SNPs. Maximum parsimony,
      maximum likelihood, NeighborNet, SVDquartets and Astral-II analyses all resulted
      in phylogenetic trees (and networks) in which interspecific relationships were
      largely unresolved. After excluding incomplete lineage sorting, hybridisation and
      oversaturation of characters as possible causes for lack of phylogenetic
      resolution, we conclude that the polytomy obtained most likely represents a hard
      polytomy. We hypothesize that diversification of Facchinia is best interpreted as
      the result of multiple simultaneous vicariance in response to climatic changes
      during the Early Quaternary.

PMID- 28433622
TI  - Diminished capacity of opsonization and immune complex solubilization, and
      detection of anti-C1q antibodies in sera from patients with hereditary
      angioedema.
AB  - BACKGROUND: Hereditary angioedema (HAE) is an autosomal dominant disease caused
      by deficiency of C1 esterase inhibitor. Symptoms of HAE include edema, which can
      potentially cause suffocation. Some patients with HAE exhibit immunological
      abnormalities, which could prevent an accurate diagnosis. Low levels of
      complement components are characteristic of HAE and in other settings are thought
      to reduce elimination of apoptotic cells and immune complex (IC). Thus, we aimed
      to experimentally clarify the mechanism of immunological abnormalities using sera
      from HAE patients. METHODS: Serum samples from 18 patients with HAE were
      collected when free from angioedema attack and compared with normal human pooled
      sera (NHPS) from 20 healthy volunteers. Opsonization was measured as the rate of
      phagocytosis of apoptotic Jurkat cells by macrophages differentiated from THP-1
      cells incubated with serum. IC solubilization in serum was analyzed by
      quantifying peroxidase released from a synthetic IC composed of peroxidase and
      anti-peroxidase antibodies. Anti-C1q antibody levels were detected using an
      enzyme-linked immunosorbent assay. RESULTS: Serological immunological
      abnormalities were detected in 12 patients. Opsonization in serum samples from
      each patient with HAE was lower than that in NHPS (~20% versus 70%,
      respectively). The rate of IC solubilization was lower in serum from HAE patients
      than NHPS. Some patients had high serum anti-C1q antibody levels with increased
      serum IC levels. CONCLUSIONS: Sera from patients with HAE exhibit anti-C1q
      antibodies, with a lower capacity for opsonization and IC solubilization. This
      may be associated with immunological abnormalities and should be investigated
      further to facilitate accurate diagnosis of HAE.

PMID- 28433623
TI  - Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the
      human brain.
AB  - Combined fMRI-MRS is a novel method to non-invasively investigate functional
      activation in the human brain using simultaneous acquisition of hemodynamic and
      neurochemical measures. The aim of the current study was to quantify neural
      activity using combined fMRI-MRS at 7T. BOLD-fMRI and semi-LASER localization MRS
      data were acquired from the visual cortex of 13 participants during short blocks
      (64s) of flickering checkerboards. We demonstrate a correlation between glutamate
      and BOLD-fMRI time courses (R=0.381, p=0.031). In addition, we show increases in
      BOLD-fMRI (1.43+/-0.17%) and glutamate concentrations (0.15+/-0.05 I.U., ~2%)
      during visual stimulation. In contrast, we observed no change in glutamate
      concentrations in resting state MRS data during sham stimulation periods.
      Spectral line width changes generated by the BOLD-response were corrected using
      line broadening. In summary, our results establish the feasibility of concurrent
      measurements of BOLD-fMRI and neurochemicals using a novel combined fMRI-MRS
      sequence. Our findings strengthen the link between glutamate and functional
      activity in the human brain by demonstrating a significant correlation of BOLD
      fMRI and glutamate over time, and by showing ~2% glutamate increases during 64s
      of visual stimulation. Our tool may become useful for studies characterizing
      functional dynamics between neurochemicals and hemodynamics in health and
      disease.

PMID- 28433625
TI  - Hemarthrosis and scurvy.

PMID- 28433626
TI  - Thrombin impairs human endometrial endothelial angiogenesis; implications for
      progestin-only contraceptive-induced abnormal uterine bleeding.
AB  - OBJECTIVE: Progestin-only contraceptives induce abnormal uterine bleeding,
      accompanied by prothrombin leakage from dilated endometrial microvessels and
      increased thrombin generation by human endometrial stromal cell (HESC)-expressed
      tissue factor. Initial studies of the thrombin-treated HESC secretome identified
      elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing
      pericyte-endothelial interactions. Thus, we investigated direct and CSPG4
      mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting
      endometrial angiogenesis. STUDY DESIGN: Liquid chromatography/tandem mass
      spectrometry, enzyme-linked immunosorbent assay (ELISA) and quantitative real
      time-polymerase chain reaction (PCR) evaluated conditioned medium supernatant and
      cell lysates from control versus thrombin-treated HESCs. Pre- and post-Depo
      medroxyprogesterone acetate (DMPA)-administered endometria were immunostained for
      CSPG4. Proliferation, apoptosis and tube formation were assessed in human
      endometrial endothelial cells (HEECs) incubated with recombinant human (rh)-CSPG4
      or thrombin or both. RESULTS: Thrombin induced CSPG4 protein expression in
      cultured HESCs as detected by mass spectrometry and ELISA (p<.02, n=3). Compared
      to pre-DMPA endometria (n=5), stromal cells in post-DMPA endometria (n=5)
      displayed stronger CSPG4 immunostaining. In HEEC cultures (n=3), total tube
      formed mesh area was significantly higher in rh-CSPG4 versus control (p<.05).
      However, thrombin disrupted HEEC tube formation by a concentration- and time
      dependent reduction of angiogenic parameters (p<.05), whereas CSPG4 co-treatment
      did not reverse these thrombin-mediated effects. CONCLUSION: These results
      suggest that disruption of HEEC tube formation by thrombin induces aberrant
      angiogenesis and abnormal uterine bleeding in DMPA users. IMPLICATIONS: Mass
      spectrometry analysis identified several HESC-secreted proteins regulated by
      thrombin. Therapeutic agents blocking angiogenic effects of thrombin in HESCs can
      prevent or minimize progestin-only contraceptive-induced abnormal uterine
      bleeding.

PMID- 28433624
TI  - Temporal slice registration and robust diffusion-tensor reconstruction for
      improved fetal brain structural connectivity analysis.
AB  - Diffusion weighted magnetic resonance imaging, or DWI, is one of the most
      promising tools for the analysis of neural microstructure and the structural
      connectome of the human brain. The application of DWI to map early development of
      the human connectome in-utero, however, is challenged by intermittent fetal and
      maternal motion that disrupts the spatial correspondence of data acquired in the
      relatively long DWI acquisitions. Fetuses move continuously during DWI scans.
      Reliable and accurate analysis of the fetal brain structural connectome requires
      careful compensation of motion effects and robust reconstruction to avoid
      introducing bias based on the degree of fetal motion. In this paper we introduce
      a novel robust algorithm to reconstruct in-vivo diffusion-tensor MRI (DTI) of the
      moving fetal brain and show its effect on structural connectivity analysis. The
      proposed algorithm involves multiple steps of image registration incorporating a
      dynamic registration-based motion tracking algorithm to restore the spatial
      correspondence of DWI data at the slice level and reconstruct DTI of the fetal
      brain in the standard (atlas) coordinate space. A weighted linear least squares
      approach is adapted to remove the effect of intra-slice motion and reconstruct
      DTI from motion-corrected data. The proposed algorithm was tested on data
      obtained from 21 healthy fetuses scanned in-utero at 22-38 weeks gestation.
      Significantly higher fractional anisotropy values in fiber-rich regions, and the
      analysis of whole-brain tractography and group structural connectivity, showed
      the efficacy of the proposed method compared to the analyses based on original
      data and previously proposed methods. The results of this study show that slice
      level motion correction and robust reconstruction is necessary for reliable in
      vivo structural connectivity analysis of the fetal brain. Connectivity analysis
      based on graph theoretic measures show high degree of modularity and clustering,
      and short average characteristic path lengths indicative of small-worldness
      property of the fetal brain network. These findings comply with previous findings
      in newborns and a recent study on fetuses. The proposed algorithm can provide
      valuable information from DWI of the fetal brain not available in the assessment
      of the original 2D slices and may be used to more reliably study the developing
      fetal brain connectome.

PMID- 28433627
TI  - Docosahexaenoic acid promotes differentiation of photoreceptor cells in three
      dimensional neural retinas.
AB  - Retinal tissues generated from human pluripotent stem cells can be an excellent
      tool for investigating pathogenesis of retinal diseases and developing new
      pharmacologic therapies. Moreover, patient derived retinal tissues could allow
      for retinal transplantation therapy for degenerative retinal diseases. However,
      obtaining retinal tissues with matured photoreceptor outer segments, which are
      essential for photoreceptor functions, is currently challenging. Here we
      investigated the effects of docosahexaenoic acid (DHA) for maturation of
      photoreceptor outer segments at the late stage and visual chromophore analog, 9
      cis-retinal for the early stage of differentiation to three-dimensional (3D)
      retinal tissues from human embryonic stem cells (hESCs), respectively. In the
      presence of DHA, differentiated 3D-retinal tissues demonstrated improved
      maturation of photoreceptor outer segments and increased number of photoreceptor
      cells compared with tissues without DHA. Increased mRNA expression of mature
      photoreceptor markers was additionally documented in retinal tissues cultured
      with DHA. Conversely supplementation with 9-cis-retinal failed to improve
      differentiation of retinal tissues perhaps due to chronic aldehyde toxicity. The
      current study demonstrated that the addition of DHA to culture medium can help
      promote differentiation of photoreceptor outer segments in vitro and utilization
      of this methodology may lead to future therapies for patients with blinding
      diseases.

PMID- 28433628
TI  - Ca2+-dependent hyperpolarization hypothesis for mammalian sleep.
AB  - The detailed molecular mechanisms underlying the regulation of sleep/wake cycles
      in mammals are elusive. In this regulation, at least two mechanisms with fast and
      slow time scales are involved. In the faster time scale, a state of non-rapid-eye
      movement (NREM) sleep can be microscopically characterized by the millisecond-to
      second-order electrical behavior of neurons, namely slow-wave oscillations
      described by electrophysiology. In the slower time scale, the total duration of
      NREM sleep is homeostatically regulated by sleep pressure (the need for sleep),
      which is usually sustained for hours or even days and can be macroscopically
      described by electroencephalogram (EEG). The longer dynamics of sleep regulation
      are often explained by the accumulation of sleep-inducing substances (SISs).
      However, we still do not have a concrete model to connect fast, microscopic
      dynamics and slow, macroscopic dynamics. In this review, we introduce a recent
      Ca2+-dependent hyperpolarization hypothesis, in which the Ca2+-dependent
      hyperpolarization of cortical-membrane potential induces slow-wave oscillation.
      Slow dynamics of the Ca2+-dependent hyperpolarization pathway might be regulated
      by recently identified sleep-promoting kinases as well as classical SISs.
      Therefore, cortical Ca2+-dependent hyperpolarization may be a fundamental
      mechanism connecting fast neural activity to the slow dynamics of sleep pressure.

PMID- 28433629
TI  - A novel strategy to dissect endogenous gene transcriptional regulation in live
      cells.
AB  - Gene transcription is a central tenet of biology, traditionally measured by RT
      PCR, microarray, or more recently, RNA sequencing. However, these measurements
      only provide a snapshot of the state of gene transcription and only represent an
      overall readout of complex transcriptional networks that regulate gene
      expression. In this report, we describe a novel strategy to dissect endogenous
      gene transcription regulation in live cells by knocking in a reporter gene, EGFP,
      under the control of the endogenous gene promoter, using the ARID1A gene as an
      example. The ARID1A gene, encoding a subunit of the ATP-dependent chromatin
      remodeling complex SNF/SWI, has recently been identified as a tumor suppressor in
      multiple cancers. Despite studies that elucidate the mechanism of ARID1A's tumor
      suppressor function, little is known of the genes/events that regulate ARID1A
      expression. Using the HEK293 cells as a model, we discovered novel aspects of
      ARID1A transcription regulation in response to cell cycle progression, DNA
      damage, and microRNAs, exemplifying the potential of our strategy in providing
      new insight to the mechanism of gene transcription regulation. This strategy can
      be generalized to essentially any gene of interest, making it a powerful tool for
      the study of gene expression heterogeneity, especially in cancer cells, and a
      robust readout for high-throughput screening of agents that modulate gene
      transcription.

PMID- 28433630
TI  - Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular
      smooth muscle cells and exacerbates abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with
      atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating
      the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal
      muscle cells and smooth muscle cells. Here, we show a novel functional role of
      MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both
      wild-type (WT) and MURC/Cavin-4 knockout (MURC-/-) mice subjected to periaortic
      application of CaCl2 developed AAAs. Six weeks after CaCl2 treatment, internal
      and external aortic diameters were significantly increased in MURC-/- AAAs
      compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica
      media of MURC-/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2
      and -9 were increased in MURC-/- AAAs compared with WT AAAs at 5 days after CaCl2
      treatment. At 6 weeks after CaCl2 treatment, MURC-/- AAAs exhibited attenuated
      JNK activity compared with WT AAAs. There was no difference in the activity of
      MMP-2 or -9 between saline and CaCl2 treatments. In MURC/Cavin-4-knockdown VSMCs,
      TNFalpha-induced activity of JNK and MMP-9 was enhanced compared with control
      VSMCs. Furthermore, WT, MURC-/-, apolipoprotein E-/- (ApoE-/-), and MURC/Cavin-4
      and ApoE double-knockout (MURC-/-ApoE-/-) mice were subjected to angiotensin II
      (Ang II) infusion. In both ApoE-/- and MURC-/-ApoE-/- mice infused for 4 weeks
      with Ang II, AAAs were promoted. The internal aortic diameter was significantly
      increased in Ang II-infused MURC-/-ApoE-/- mice compared with Ang II-infused ApoE
      /- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP
      9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4
      in VSMCs modulates AAA progression at the early stage via the activation of JNK
      and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA
      progression.

PMID- 28433631
TI  - Detection of cAMP and of PKA activity in Saccharomyces cerevisiae single cells
      using Fluorescence Resonance Energy Transfer (FRET) probes.
AB  - In Saccharomyces cerevisiae the second messenger cyclic adenosine monophosphate
      (cAMP) and protein kinase A (PKA) play a central role in metabolism regulation,
      stress resistance and cell cycle progression. To monitor cAMP levels and PKA
      activity in vivo in single S. cerevisiae cells, we expressed an Epac-based FRET
      probe and a FRET-based A-kinase activity reporter, which were proven to be useful
      live-cell biosensors for cAMP levels and PKA activity in mammalian cells.
      Regarding detection of cAMP in single yeast cells, we show that in wild type
      strains the CFP/YFP fluorescence ratio increased immediately after glucose
      addition to derepressed cells, while no changes were observed when glucose was
      added to a strain that is not able to produce cAMP. In addition, we had evidence
      for damped oscillations in cAMP levels at least in SP1 strain. Regarding
      detection of PKA activity, we show that in wild type strains the FRET increased
      after glucose addition to derepressed cells, while no changes were observed when
      glucose was added to either a strain that is not able to produce cAMP or to a
      strain with absent PKA activity. Taken together these probes are useful to follow
      activation of the cAMP/PKA pathway in single yeast cells and for long times (up
      to one hour).

PMID- 28433632
TI  - Role of microRNA-130b in placental PGC-1alpha/TFAM mitochondrial biogenesis
      pathway.
AB  - Diabetes during pregnancy is associated with abnormal placenta mitochondrial
      function and increased oxidative stress, which affect fetal development and
      offspring long-term health. Peroxisome proliferator-activated receptor-gamma
      coactivator-1alpha (PGC-1alpha) is a master regulator of mitochondrial biogenesis
      and energy metabolism. The molecular mechanisms underlying the regulation of PGC
      1alpha in placenta in the context of diabetes remain unclear. The present study
      examined the role of microRNA 130b (miR-130b-3p) in regulating PGC-1alpha
      expression and oxidative stress in a placental trophoblastic cell line (BeWo).
      Prolonged exposure of BeWo cells to high glucose mimicking hyperglycemia resulted
      in decreased protein abundance of PGC-1alpha and its downstream factor,
      mitochondrial transcription factor A (TFAM). High glucose treatment increased the
      expression of miR-130b-3p in BeWo cells, as well as exosomal secretion of miR
      130b-3p. Transfection of BeWo cells with miR-130b-3p mimic reduced the abundance
      of PGC-1alpha, whereas inhibition of miR-130b-3p increased PGC-1alpha expression
      in response to high glucose, suggesting a role for miR-130b-3p in mediating high
      glucose-induced down regulation of PGC-1alpha expression. In addition, miR-130b
      3p anti-sense inhibitor increased TFAM expression and reduced 4-hydroxynonenal (4
      HNE)-induced production of reactive oxygen species (ROS). Taken together, these
      findings reveal that miR-130b-3p down-regulates PGC-1alpha expression in
      placental trophoblasts, and inhibition of miR-130b-3p appears to improve
      mitochondrial biogenesis signaling and protect placental trophoblast cells from
      oxidative stress.

PMID- 28433633
TI  - Angiotensin-converting enzyme 2 is a potential therapeutic target for EGFR-mutant
      lung adenocarcinoma.
AB  - EGFR-mutant lung adenocarcinomas contain a subpopulation of cells that have
      undergone epithelial-to-mesenchymal transition and can grow independently of
      EGFR. To kill these cancer cells, we need a novel therapeutic approach other than
      EGFR inhibitors. If a molecule is specifically expressed on the cell surface of
      such EGFR-independent EGFR-mutant cancer cells, it can be a therapeutic target.
      We found that a mesenchymal EGFR-independent subline derived from HCC827 cells,
      an EGFR-mutant lung adenocarcinoma cell line, expressed angiotensin-converting
      enzyme 2 (ACE2) to a greater extent than its parental cells. ACE2 was also
      expressed at least partially in most of the primary EGFR-mutant lung
      adenocarcinomas examined, and the ACE2 expression level in the cancer cells was
      much higher than that in normal lung epithelial cells. In addition, we developed
      an anti-ACE2 mouse monoclonal antibody (mAb), termed H8R64, that was internalized
      by ACE2-expressing cells. If an antibody-drug conjugate consisting of a humanized
      mAb based on H8R64 and a potent anticancer drug were produced, it could be
      effective for the treatment of EGFR-mutant lung adenocarcinomas.

PMID- 28433634
TI  - Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil
      in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R
      signalling.
AB  - Hepatocellular carcinoma (HCC) represents the third leading cause of cancer
      related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first
      choice treatment for advanced HCC, it exerts poor efficacy and is associated with
      acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour
      promoting roles in different cancer types including HCC and thus represent
      promising pharmacological targets. In the present study, we have investigated for
      the first time the anticancer efficacy and underlying molecular mechanisms of
      combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4
      chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma
      cells. Here, we report that co-administration of 5-FU and SKI-II at low sub-toxic
      concentrations of 20 MUM and 5 MUM, respectively, synergistically inhibit cell
      proliferation, markedly reduce cell migration and the clonogenic survival, and
      increase apoptosis induction in HepG2 cells. Additional Western blot analyses
      have shown that possible mechanisms underlying enhanced sensitivity to 5-FU
      induced by dual Sphk 1/2 inhibition could include abrogation of FAK-regulated IGF
      1R activity and down-regulation of osteopontin expression culminating in the
      inhibition of NF-kappaB activity and its downstream signalling mediated by
      sirtuin 1 and p38 MAPK. Our results clearly show that pharmacological blockade of
      both Sphk isoforms represents a promising strategy to boost the anti-tumour
      efficacy of 5-FU and provide a rationale for further in vivo studies into the
      possible use of SKI-II inhibitor as an adjunct to 5-FU treatment in HCC.

PMID- 28433635
TI  - Prognostic significance and functional implication of immune activating receptor
      NKG2D in gastric cancer.
AB  - NKG2D, an activating receptor expressed on CD8+ T lymphocytes, serves as a co
      stimulation molecule by engagement with its ligands MICA/B and ULBPs to trigger
      immune activation against tumors. Currently, the biological function and clinical
      significance of NKG2D in gastric cancer remains unexplored. The study aims to
      investigate the expression of NKG2D in gastric cancer in association with
      clinical prognosis and its biological function. Real-time PCR was used to analyze
      NKG2D expression in paired cancer and adjacent non-malignant tissues in 139
      gastric cancer patients between 2007 and 2010 in Shanghai Cancer Center. NKG2D
      expression showed no association with any clinical characteristic parameters.
      High NKG2D level was significantly associated with better outcome (P = 0.018 for
      OS, P = 0.041 for DFS). Using univariate Cox regression model, high NKG2D mRNA
      resulted in 43% risk reduction in gastric cancer patients (HR = 0.57, CI (0.36
      0.91), P = 0.019). High NKG2D level displayed a significant association with
      longer OS in the multivariate analysis (HR = 0.59, CI (0.363-0.96), P = 0.034),
      independent of other prognostic factors including Lauren classification, neural
      infiltration, vascular/lymphatic invasion, TNM stage. Upon co-incubation with
      cancer cells, NKG2D expression in CD8+ T cells was markedly down-regulated.
      Functional study suggested that either blocking NKG2D or its ligand ULBP-2 could
      suppress tumor-killing activity of CD8+ T cells. Our data showed that NKG2D
      receptor could be an independent favorable prognostic indicator for gastric
      cancer. Furthermore, decreased NKG2D expression might be the mechanism underlying
      immune evasion by tumors in gastric cancer.

PMID- 28433636
TI  - Malassezia globosa MgMDL2 lipase: Crystal structure and rational modification of
      substrate specificity.
AB  - Lipases play an important role in physiological metabolism and diseases, and also
      have multiple industrial applications. Rational modification of lipase
      specificity may increase the commercial utility of this group of enzymes, but is
      hindered by insufficient mechanistic understanding. Here, we report the 2.0 A
      resolution crystal structure of a mono- and di-acylglycerols lipase from
      Malassezia globosa (MgMDL2). Interestingly, residues Phe278 and Glu282 were found
      to involve in substrate recognition because mutation on each residue led to
      convert MgMDL2 to a triacylglycerol (TAG) lipase. The Phe278Ala and Glu282Ala
      mutants also acquired ability to synthesize TAGs by esterification of glycerol
      and fatty acids. By in silicon analysis, steric hindrance of these residues
      seemed to be key factors for the altered substrate specificity. Our work may shed
      light on understanding the unique substrate selectivity mechanism of mono- and di
      acylglycerols lipases, and provide a new insight for engineering biocatalysts
      with desired catalytic behaviors for biotechnological application.

PMID- 28433637
TI  - Inhibition of pro-inflammatory enzymes by medicinal plants from the Argentinean
      highlands (Puna).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Human groups in the Argentinean Andes highlands
      (Puna) selected native plants as anti-inflammatory agents. The indications of use
      are mainly to relieve pain, as infusions, ethanolic extracts or plasters. AIM OF
      THE STUDY: The objective of the study was to assess the effect of hydroalcoholic
      extracts from native highland plants as anti-inflammatory agents according to the
      traditional indications of use. The chemical profile of the three most active
      species was analyzed by HPLC-ESI-MS to get an insight into the constituents and
      the effects observed according to the ethnopharmacological information. MATERIALS
      AND METHODS: Hydroalcoholic extracts from 13 Argentinean Puna plants used as anti
      inflammatory were evaluated as inhibitors of the pro-inflammatory enzymes
      phospholipase A2 (sPLA2), lipoxygenase (LOX), hyaluronidase, and for their
      capacity to stabilize red blood cells membrane. In addition, the extracts were
      evaluated to determine their reducing power, iron chelating capacity and ABTS*+
      radical scavenging effect. The chemical profiles of the most active species were
      analyzed by HPLC-ESI-MS. RESULTS: Among the species investigated, Ephedra
      multiflora was the most active as LOX inhibitor (IC50:132ug/mL), by reducing the
      non-heme iron group and by scavenging radicals. The IC50 values of the reference
      compounds caffeic acid and naproxen were 57.0 and 14.0ug/mL, respectively.
      Parastrephia lucida showed the highest sPLA2 inhibitory effect (63% of inhibition
      at 200ug/mL). Under the same experimental conditions, the IC50 of the reference
      compound acetylsalicylic acid was 65+/-1ug/mL. Tessaria absinthioides exhibited
      the best inhibition towards hyaluronidase with an IC50 of 93.2+/-4.3ug/mL. Under
      the same experimental conditions, the reference compounds quercetin and
      indomethacin presented IC50 values of 340.0+/-17.0 and 502.0+/-10.0ug/mL,
      respectively. Among the most active species, 13 compounds were tentatively
      identified by HPLC-ESI-MS in E. multiflora and P. lucida, and 12 compounds in T.
      absinthioides. The constituents included caffeoyl- and feruloylquinic acid
      derivatives, flavonoids, simple phenolics and sesquiterpene glycosides.
      CONCLUSIONS: Six out of the 13 species investigated showed a moderate to strong
      effect towards the enzyme sPLA2 (>40% inhibition at 200ug/mL) while three species
      presented a strong activity against LOX with IC50<250ug/mL and three were very
      active against hyaluronidase. Most of the crude drug extracts were able to
      stabilize the red blood cells membrane, preventing their lysis. The compounds
      identified in the extracts explain, at least in part, the activity found in the
      samples. The effect observed for the most active species supports their
      traditional use as anti-inflammatory agents. However, more studies should be
      undertaken to disclose the potential of the Puna plants as anti-inflammatory
      crude drugs.

PMID- 28433638
TI  - Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in
      rats.
AB  - Pesticides and heavy metals are widespread environmental pollutants. Although the
      acute toxicity of organophosphorus pesticide chlorpyrifos (CPF) and toxic heavy
      metal cadmium (Cd) is well characterized, the combined toxicity of CPF and Cd,
      especially the hepatotoxicity of the two chemicals with long-term exposure at a
      low dose, remained unclear. In this study, we investigated the toxicity in the
      liver of rats upon subchronic exposure to CPF and Cd at environmentally relevant
      doses. Rats were given three different doses (1/135 LD50, 1/45 LD50 and 1/15
      LD50) of CPF and Cd as well as their mixtures by oral gavage for 90days. After
      treatment, the liver tissues were subjected to histopathological examination and
      biochemical analysis. Gas chromatography-mass spectrometry (GC-MS) was used to
      analyze the metabolomic changes in the rat liver upon CPF, Cd and their mixtures
      treatment. The results showed that CPF and Cd-induced oxidative damage and
      disrupted energy, amino acid, and fatty acid metabolism in the liver. Eleven
      biomarkers in liver were identified for CPF-, Cd-, and their mixture-treated
      rats. Three metabolites, i.e., butanedioic acid, myo-inositol, and urea, were
      identified as unique biomarkers for the mixture-treated rats. Moreover, we found
      that Cd could accelerate the metabolism of CPF in the liver when given together
      to the rats, which may lead to the potential antagonistic interaction between CPF
      and Cd. In conclusion, our results indicated that even at environmentally
      relevant doses, CPF and Cd could disrupt the liver metabolism. In addition, the
      accelerated metabolism of CPF by Cd may lead to their potential antagonistic
      interaction.

PMID- 28433639
TI  - Optimization of atrazine and imidacloprid removal from water using biochars:
      Designing single or multi-staged batch adsorption systems.
AB  - BACKGROUND: Contamination of surface and ground water by pesticides from
      agricultural runoff and industrial discharge is one of the main causes of aqueous
      contaminations world over. Biochar, agricultural waste derived highly aromatic
      substance produced after pyrolysis and carbonification of biomass have exhibited
      good adsorption capacity for pesticides and can be used to develop on-site bio
      purification systems for organic contaminant removal from polluted waters.
      However, high amounts of adsorbent required in single stage-batch sorption plant
      increases the cost of water treatment; therefore, multistage plant systems were
      investigated. METHODS: Normal (RSBC) and phosphoric acid treated (T-RSBC) rice
      straw biochars were evaluated for atrazine and imidacloprid sorption and data
      fitted to the Freundlich isotherm. The adsorption data was modelled to develop
      single or multi-staged adsorber plants for pesticide removal from water. RESULTS:
      Both biochars showed significantly high adsorption capacity for imidacloprid and
      atrazine. Modelling studies using the Freundlich adsorption parameters suggested
      that the amounts (kg/1000L) of RSBC and T-RSBC for 95% of atrazine removal
      (10mg/L) in single-, two- and three-staged adsorber plant models were 8.84, 2.44,
      1.61kg and 4.47, 1.42, 0.98kg, respectively. Corresponding amounts for 95%
      imidacloprid removal (10mg/L) were 3.97, 1.22, 0.84kg and 3.98, 1.38, 0.96kg,
      respectively. Thus, the two-staged model suggested 65-72% reduction in amount of
      adsorbent required over the single stage model, while the three-staged model
      suggested 30-34% adsorbent saving over the two-staged plant model. Single and two
      staged adsorber plant model findings were validated for atrazine removal using T
      RSBC. Results suggested that amounts calculated using modelling studies were
      fairly accurate. CONCLUSION: Biochars, as low cost adsorbents for atrazine and
      imidacloprid removal from contaminated water, can be used to develop low cost
      adsorber plants based on multiple batch sorption systems for the removal of these
      pesticides. Upscaled use of the 2-stage adsorber plant model will substantially
      reduce the cost of the treatment process, especially at pesticide concentration
      <10mg/L as lesser amounts of biochar will be used for treatment process.

PMID- 28433640
TI  - Partial Gland Treatment of Prostate Cancer Using High-Intensity Focused
      Ultrasound in the Primary and Salvage Settings: A Systematic Review.
AB  - PURPOSE: Advances in prostate imaging, biopsy and ablative technologies have been
      accompanied by growing enthusiasm for partial gland ablation, particularly using
      high-intensity focused ultrasound, to treat prostate cancer. Preserving
      noncancerous prostate tissue and minimizing damage to the neurovascular bundles
      and external urethral sphincter may improve functional outcomes. MATERIALS AND
      METHODS: A systematic review was performed following PRISMA (Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses) guidelines using a combination of
      MeSH(r) terms, free text search and examination of relevant bibliographies using
      MEDLINE(r) and Embase(r) from the inception of each database through October 10,
      2016. We excluded studies describing exclusively whole gland ablation, case
      reports and series where treatment was followed by immediate resection. RESULTS:
      A total of 13 studies that enrolled 543 patients were included. Of the studies 11
      were performed in the primary setting and 2 in the salvage setting. Median
      followup ranged from 6 months to 10.6 years. Rates of posttreatment erectile
      dysfunction and urinary incontinence ranged from 0% to 48% and 0% to 50%,
      respectively, with definitions varying by study. Overall there were 254 reported
      complications. Marked heterogeneity between studies limited the ability to pool
      results regarding functional and oncologic outcomes. A total of 76 patients (14%)
      subsequently received further oncologic treatment. CONCLUSIONS: Early evidence
      suggests that partial gland ablation is a safe treatment option for men with
      localized disease. Longer term data are needed to evaluate oncologic efficacy and
      functional outcomes, and will aid in identifying the optimal candidates for
      therapy. Standardization of outcomes definitions will allow for better comparison
      between studies and among treatment modalities.

PMID- 28433641
TI  - Analysis of Complications of Pelvic Mesh Excision Surgery Using the Clavien-Dindo
      Classification System.
AB  - PURPOSE: We describe and categorize complications using the Clavien-Dindo
      classification system in patients who underwent vaginal mesh excision surgery.
      MATERIALS AND METHODS: With institutional review board approval we
      retrospectively reviewed the records of 277 patients who underwent vaginal mesh
      extraction between 2007 and 2015 at a single institution. Surgical complications
      were stratified using the Clavien-Dindo classification system. Complications were
      perioperative (prior to discharge) or postoperative (within 90 days). Indications
      for initial mesh placement, mesh revision procedure, time to resolution and
      medical comorbidities were assessed. RESULTS: Of the 277 patients 47.3% had at
      least 1 surgical complication, including multiple complications in 7.2%. A total
      of 155 complications were identified, which were grade II in 49.0% of cases,
      grade I in 25.8%, grade IIIb in 18.7%, grade IIIa in 5.2% and grade IVa in 1.3%.
      No grade IVb or V complications were identified. The indication for initial mesh
      placement did not significantly affect complication frequency. Patients who
      underwent combined stress urinary incontinence and pelvic organ prolapse mesh
      revision surgeries had an increased frequency of complications compared to those
      treated with mesh revision surgery for pelvic organ prolapse or stress urinary
      incontinence alone (p = 0.045). Most complications occurred postoperatively and
      resolved by 90 days. Age, body mass index, smoking status and diabetes were not
      associated with increased complications. CONCLUSIONS: Despite the complexity of
      mesh revision surgery most complications are minor. Serious complications may
      develop, emphasizing the need for proper patient counseling and surgical
      experience when performing these procedures.

PMID- 28433642
TI  - Predicting Nonmuscle Invasive Bladder Cancer Recurrence and Progression in a
      United States Population.
AB  - PURPOSE: We assessed the performance of the EORTC (European Organisation for
      Research and Treatment of Cancer) and CUETO (Club Urologico Espanol de
      Tratamiento Oncologico) nonmuscle invasive bladder cancer predictive models
      compared to current United States NCCN Guidelines(r) in an American population.
      MATERIALS AND METHODS: We retrospectively analyzed the electronic medical records
      of patients with nonmuscle invasive bladder cancer in a multicenter population in
      the United States. We evaluated recurrence-free and progression-free survival
      according to EORTC and CUETO, and assessed discriminative performance with the c
      index at 1 and 5 years. We then compared the discrimination of EORTC and CUETO to
      the discrimination of the 4 nonmuscle invasive bladder cancer treatment groups
      described in NCCN Guidelines. RESULTS: We identified 1,333 patients with
      nonmuscle invasive bladder cancer and a median followup of 37 months. At 5 years
      the recurrence c-index of EORTC and CUETO was 0.59 and 0.56 while for progression
      it was higher at 0.74 and 0.72, respectively. NCCN Guidelines demonstrated a
      similar c-index of 0.56 and 0.75, respectively. The discrimination of all 3 risk
      models decreased in patients who received bacillus Calmette-Guerin. EORTC was
      better able to identify patients at low risk for recurrence or progression but it
      overestimated the 5-year risk of progression in patients at high risk. This study
      was limited by its retrospective design. CONCLUSIONS: Our work illustrates the
      need for improved predictive tools for clinicians who treat patients with
      nonmuscle invasive bladder cancer. However, until new tools are developed NCCN
      Guidelines are a simple option for clinicians who treat patients with nonmuscle
      invasive bladder cancer. Those guidelines provide predictive power comparable to
      that of the EORTC and CUETO models.

PMID- 28433643
TI  - Green light for lipid fingerprinting.
AB  - The use of targeted lipidomic approaches for the analysis of plant lipids has
      steadily increased during recent years. We review recent developments of these
      methods and suggest the introduction of discovery lipidomics as additional
      approach through a new workflow, lipid fingerprinting, that integrates the
      advantages of shotgun lipidomics (quantitative data) with LC-MS-based strategies
      (higher resolution and/or coverage). This article is part of a Special Issue
      entitled:BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.

PMID- 28433645
TI  - Cranberry Capsules do not Appear to Reduce Bacteriuria and Pyuria in Elderly
      Women Residing in Nursing Homes.

PMID- 28433646
TI  - Therapeutic Intention: Into the Next Generation.

PMID- 28433647
TI  - [Two siblings with acute lymphoblastic leukaemia: chance or genetics?]

PMID- 28433644
TI  - Supraspinal respiratory plasticity following acute cervical spinal cord injury.
AB  - Impaired breathing is a devastating result of high cervical spinal cord injuries
      (SCI) due to partial or full denervation of phrenic motoneurons, which innervate
      the diaphragm - a primary muscle of respiration. Consequently, people with
      cervical level injuries often become dependent on assisted ventilation and are
      susceptible to secondary complications. However, there is mounting evidence for
      limited spontaneous recovery of respiratory function following injury,
      demonstrating the neuroplastic potential of respiratory networks. Although many
      studies have shown such plasticity at the level of the spinal cord, much less is
      known about the changes occurring at supraspinal levels post-SCI. The goal of
      this study was to determine functional reorganization of respiratory neurons in
      the medulla acutely (>4h) following high cervical SCI. Experiments were conducted
      in decerebrate, unanesthetized, vagus intact and artificially ventilated rats. In
      this preparation, spontaneous recovery of ipsilateral phrenic nerve activity was
      observed within 4 to 6h following an incomplete, C2 hemisection (C2Hx).
      Electrophysiological mapping of the ventrolateral medulla showed a reorganization
      of inspiratory and expiratory sites ipsilateral to injury. These changes included
      i) decreased respiratory activity within the caudal ventral respiratory group
      (cVRG; location of bulbospinal expiratory neurons); ii) increased proportion of
      expiratory phase activity within the rostral ventral respiratory group (rVRG;
      location of inspiratory bulbo-spinal neurons); iii) increased respiratory
      activity within ventral reticular nuclei, including lateral reticular (LRN) and
      paragigantocellular (LPGi) nuclei. We conclude that disruption of descending and
      ascending connections between the medulla and spinal cord leads to immediate
      functional reorganization within the supraspinal respiratory network, including
      neurons within the ventral respiratory column and adjacent reticular nuclei.

PMID- 28433648
TI  - Repeated threat (without direct harm) alters metabolic capacity in select regions
      that drive defensive behavior.
AB  - To understand the behavioral consequences of intermittent anticipatory stress
      resulting from threats without accompanying physiological challenges, we
      developed a semi-naturalistic rodent housing and foraging environment that can
      include threats that are unpredictable in timing. Behavior is automatically
      recorded while rats forage for food or water. Over three weeks, the threats have
      been shown to elicit risk assessment behaviors, increase defensive burying and
      increase adrenal gland weight. To identify brain regions activated by this
      manipulation, we measured cytochrome c oxidase (COX), which is tightly coupled to
      neural activity. Adolescent male Sprague-Dawley rats were randomly assigned to
      control (CT) or unpredictable threat/stress (ST) housing conditions consisting of
      two tub cages, one with food and another with water, separated by a tunnel. Over
      three weeks (P31-P52), the ST group received randomly timed (probability of
      0.25), simultaneous presentations of ferret odor, an abrupt light, and sound at
      the center of the tunnel. The ST group had consistently fewer tunnel crossings
      than the CT group, but similar body weights. Group differences in COX activity
      were detected in regions implicated in the control of defensive burying. There
      was an increase in COX activity in the hypothalamic premammillary dorsal nucleus
      (PMD) and lateral septum (LS), whereas a decrease was observed in the
      periaqueductal gray (PAG) and CA3 region of the hippocampus. There were no
      significant differences in the anterior cingulate cortex, prefrontal cortex,
      striatum or motor cortex. The sites with changes in metabolic capacity are
      candidates for the sites of plasticity that may underlie the behavioral
      adaptations to intermittent threats.

PMID- 28433649
TI  - Chronic nicotine attenuates behavioral and synaptic plasticity impairments in a
      streptozotocin model of Alzheimer's disease.
AB  - Brain glucose metabolism is altered in sporadic Alzheimer's disease (sAD), whose
      pathologies are reproduced in rodents by intracerebroventricular (icv) infusion
      of streptozotocin (STZ) in subdiabetogenic doses. The icv-STZ model also
      culminates in central cholinergic dysfunctions, which in turn are known to
      underlie both the sAD cognitive decline, and synaptic plasticity impairments.
      Considering the cognitive-enhancing potential of chronic nicotine (Nic), we
      investigated whether it attenuates icv-STZ-induced impairments in recognition
      memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal
      CA1-medial prefrontal cortex (mPFC) pathway. Rats treated with icv-STZ were
      submitted to a chronic Nic regime, and were evaluated for recognition memory. We
      then examined long-term potentiation (LTP), paired-pulse facilitation (PPF) under
      urethane anesthesia, and brains were also evaluated for hippocampus-mPFC cell
      density. We found that Nic treatment prevents icv-STZ-induced disruptions in
      recognition memory and LTP. STZ did not precipitate neuronal death, while Nic
      alone was associated with higher neuronal density in CA1 when compared to vehicle
      injected animals. Through combining behavioral, neurophysiological, and
      neuropathological observations into the Nic-STZ interplay, our study reinforces
      that cholinergic treatments are of clinical importance against early-stage
      Alzheimer's disease and mild cognitive impairments.

PMID- 28433650
TI  - Long noncoding RNA Malat1 is a potent autophagy inducer protecting brain
      microvascular endothelial cells against oxygen-glucose deprivation/reoxygenation
      induced injury by sponging miR-26b and upregulating ULK2 expression.
AB  - Brain microvascular endothelial cell (BMEC) injury induced by ischemia
      reperfusion (I/R) is the initial stage of blood-brain barrier (BBB) disruption,
      which results in a poor prognosis in ischemic stroke patients. Autophagy has been
      shown to have protective effects on BMECs against cerebral ischemic insults.
      However, molecular mechanism of BMEC autophagy during I/R is unclear. Long
      noncoding RNAs (lncRNAs) are emerging as new factors involved in cell autophagy.
      LncRNA Malat1 is one of the most highly upregulated I/R or OGD/R-responsive
      endothelial lncRNA and plays a protective role in BMECs against cerebral ischemic
      insults. Oxygen-glucose deprivation/reoxygenation (OGD/R) is used to mimic I/R
      injury in vitro. Based on these findings, we hypothesized that Malat1 might play
      a protective role by enhancing BMEC autophagy. We performed GFP-LC3 puncta
      formation, LC3 conversion, p62 expression, and cell death assays, and the results
      were consistent with our hypothesis that Malat1 promoted BMEC autophagy and
      survival under OGD/R condition. We further explored the molecular mechanisms by
      which Malat1 exerted regulatory effects, and found that Malat1 served as an
      endogenous sponge to downregulate miR-26b expression by binding directly to miR
      26b. Furthermore, Malat1 overturned the inhibitory effect of miR-26b on BMEC
      autophagy and survival, which involved in promoting the expression of miR-26b
      target ULK2. Collectively, our study illuminated a new Malat1-miR-26b-ULK2
      regulatory axis in which Malat1 served as a competing endogenous RNA by sponging
      miR-26b and upregulating ULK2 expression, thereby promoting BMEC autophagy and
      survival under OGD/R condition.

PMID- 28433651
TI  - The surge of predatory open-access in neurosciences and neurology.
AB  - Predatory open access is a controversial publishing business model that exploits
      the open-access system by charging publication fees in the absence of transparent
      editorial services. The credibility of academic publishing is now seriously
      threatened by predatory journals, whose articles are accorded real citations and
      thus contaminate the genuine scientific records of legitimate journals. This is
      of particular concern for public health since clinical practice relies on the
      findings generated by scholarly articles. Aim of this study was to compile a list
      of predatory journals targeting the neurosciences and neurology disciplines and
      to analyze the magnitude and geographical distribution of the phenomenon in these
      fields. Eighty-seven predatory journals operate in neurosciences and 101 in
      neurology, for a total of 2404 and 3134 articles issued, respectively.
      Publication fees range 521-637 USD, much less than those charged by genuine open
      access journals. The country of origin of 26.0-37.0% of the publishers was
      impossible to determine due to poor websites or provision of vague or non
      credible locations. Of the rest 35.3-42.0% reported their headquarters in the
      USA, 19.0-39.2% in India, 3.0-9.8% in other countries. Although calling
      themselves "open-access", none of the journals retrieved was listed in the
      Directory of Open Access Journals. However, 14.9-24.7% of them were found to be
      indexed in PubMed and PubMed Central, which raises concerns on the criteria for
      inclusion of journals and publishers imposed by these popular databases. Scholars
      in the neurosciences are advised to use all the available tools to recognize
      predatory practices and avoid the downsides of predatory journals.

PMID- 28433652
TI  - Ketamine potentiates oxidative stress and influences behavior and inflammation in
      response to lipolysaccharide (LPS) exposure in early life.
AB  - Immune activation (IA) during the early neonatal period is a risk factor for the
      development of schizophrenia. Lipopolysaccharide (LPS) injected in neonates lead
      to behavioral and brain changes that persist to adult life. We investigated
      oxidative stress, levels of cytokines, and the locomotor activity of IA in a
      schizophrenia animal model in which neonatal male Wistar rats were administered
      with an injection of LPS (50MUg/kg) on postnatal day 3 and different doses of
      ketamine (5, 15 and 25mg/kg) for 7days during adulthood. Rats LPS-induced did not
      have locomotor activity alterations. Locomotor activity was elevated in
      neonatally saline-injected in the higher dose ketamine-treated animals. Carbonyl
      protein in the prefrontal cortex (PFC), hippocampus and striatum were increased
      in the LPS- and saline-induced in the ketamine (25mg/kg)-treated animals. Lipid
      damage occurred in the PFC, striatum and hippocampus in the LPS- and saline
      induced in the ketamine (15 and 25mg/kg) -treated animals. In the hippocampus the
      superoxide dismutase (SOD) was decreased in the LPS- and saline-induced in the
      ketamine-treated with the dose of 25mg/kg. In the PFC SOD was reduced in the LPS
      induced in the ketamine (25mg/kg)-treated animals. Catalase in the PFC and
      hippocampus was reduced in the LPS- and saline-induced in the ketamine (25mg/kg)
      treated animals. Pro- and anti-inflammatory cytokines were lower in the brains of
      LPS-induced in the higher dose ketamine-treated rats. IA influences the locomotor
      activity and cytokine levels induced by ketamine, and it has a negative effect in
      potentiating the oxidative stress by higher doses of ketamine in the brain.

PMID- 28433653
TI  - Self-awareness and the medial temporal lobe in neurodegenerative diseases.
AB  - Accurate self-awareness is essential for adapting one's behaviour to one's actual
      abilities, to avoid risky behaviour. Impaired self-awareness of deficits is
      common in neurodegenerative diseases. Numerous studies show an involvement of
      midline cortical areas in impaired self-awareness. Among the other brain regions
      implicated stand the medial temporal lobe (MTL) structures (i.e. hippocampus,
      amygdala, and temporopolar, entorhinal, perirhinal and posterior parahippocampal
      cortices). This review aims at evaluating the role of those structures in self
      awareness in neurodegenerative diseases. To this aim, we briefly review impaired
      self-awareness in neurodegenerative diseases, give a neuroanatomical background
      on the MTL structures, and report those identified in neuroimaging studies on
      self-awareness. The MTL shows neuropathological, and structural or functional
      changes in patients who overestimate their abilities in the cognitive, socio
      emotional or daily life activities domains. The structures implicated differ
      depending on the domain considered, suggesting a modality-specific involvement.
      The functional significance of the findings is discussed in view of the
      neuroanatomical networks of the MTL and in the context of theoretical models of
      self-awareness.

PMID- 28433654
TI  - High molecular weight FGF2 isoforms demonstrate canonical receptor-mediated
      activity and support human embryonic stem cell self-renewal.
AB  - Basic fibroblast growth factor (FGF2) is a highly pleiotropic member of a large
      family of growth factors with a broad range of activities, including mitogenesis
      and angiogenesis (Ornitz et al., 1996; Zhang et al., 2006), and it is known to be
      essential for maintenance of balance between survival, proliferation, and self
      renewal in human pluripotent stem cells (Eiselleova et al., 2009; Zoumaro-Djayoon
      et al., 2011). A single FGF2 transcript can be translated into five FGF2 protein
      isoforms, an 18kDa low molecular weight (LMW) isoform and four larger high
      molecular weight (HMW) isoforms (Arese et al., 1999; Arnaud et al., 1999). As
      they are not generally secreted, high molecular weight (HMW) FGF2 isoforms have
      predominantly been investigated intracellularly; only a very limited number of
      studies have investigated their activity as extracellular factors. Here we report
      over-expression, isolation, and biological activity of all recombinant human FGF2
      isoforms. We show that HMW FGF2 isoforms can support self-renewal of human
      embryonic stem cells (hESCs) in vitro. Exogenous supplementation with HMW FGF2
      isoforms also activates the canonical FGFR/MAPK pathway and induces mitogenic
      activity in a manner similar to that of the 18kDa FGF2 isoform. Though all HMW
      isoforms, when supplemented exogenously, are able to recapitulate LMW FGF2
      activity to some degree, it appears that certain isoforms tend to do so more
      poorly, demonstrating a lesser functional response by several measures. A better
      understanding of isoform-specific FGF2 effects will lead to a better
      understanding of developmental and pathological FGF2 signaling.

PMID- 28433655
TI  - Targeting sarcoma tumor-initiating cells through differentiation therapy.
AB  - Human leukocyte antigen class I (HLA-I) down-regulation has been reported in many
      human cancers to be associated with poor clinical outcome. However, its
      connection to tumor-initiating cells (TICs) remains unknown. In this study, we
      report that HLA-I is down-regulated in a subpopulation of cells that have high
      tumor initiating capacity in different types of human sarcomas. Detailed
      characterization revealed their distinct molecular profiles regarding
      proliferation, apoptosis and stemness programs. Notably, these TICs can be
      induced to differentiate along distinct mesenchymal lineages, including the
      osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed
      in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced
      osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting
      in significantly decreased tumor formation. Thus, our findings indicate down
      regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and
      differentiation therapy strategies may specifically target undifferentiated TICs
      and inhibit tumor formation.

PMID- 28433657
TI  - miR-938 promotes colorectal cancer cell proliferation via targeting tumor
      suppressor PHLPP2.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths
      worldwide. Although the development of therapy approaches, the outcome of CRC
      patients still is poor, understanding the biological mechanism of CRC progression
      is critical to improve the treatment strategies. miRNAs regulate CRC progression,
      we found miR-938 was upregulated in CRC tissues and cells, MTT assay, colony
      formation assay and soft agar growth assay suggested miR-938 overexpression
      promoted CRC cell proliferation, miR-938 knockdown inhibited CRC cell
      proliferation. Tumor suppressor PH domain Leucine-rich-repeats Protein
      Phosphatase 2 (PHLPP2) was a target of miR-938, miR-938 inhibited PHLPP2,
      luciferase activity assay suggested miR-938 directly bound to the 3'UTR of
      PHLPP2, meanwhile, we found miR-938 promoted c-Myc and Cyclin D1 expression,
      confirming miR-938 promoted CRC cell proliferation. Double knockdown of miR-938
      and PHLPP2 promoted CRC cell proliferation, suggesting miR-938 promoted CRC cell
      proliferation by inhibiting PHLPP2.

PMID- 28433656
TI  - Impaired endothelium-derived hyperpolarization-type relaxation in superior
      mesenteric arteries isolated from female Otsuka Long-Evans Tokushima Fatty rats.
AB  - Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism
      of endothelium-dependent vasorelaxation, and little attention has been paid to
      the EDH-type responses in female metabolic syndrome such as that observed with
      type-2 diabetes. We previously reported that EDH-type relaxation was impaired in
      superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF)
      rat, a model of type-2 diabetes, however, the response was unclear in female
      OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was
      altered in superior mesenteric arteries isolated from female OLETF rats compared
      to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50
      59 weeks. We investigated concentration-relaxation curves for acetylcholine (at
      age 50-53 weeks), NS309 (an activator of small- and intermediate-conductance
      calcium-activated potassium channels) (at age 50-53 weeks), and GSK1016790A (an
      agonist of transient receptor potential vanilloid type 4, TRPV4) (at age 58 or 59
      weeks) in the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine
      and the cyclooxygenase inhibitor indomethacin to investigate EDH-type responses
      in the superior mesenteric artery. Obesity, mild hyperglycemia, hyperinsulinemia,
      and hyperlipidemia (i.e., increased total cholesterol, triglyceride, and non
      esterified fatty acids) were more frequent in OLETF rats than in age-matched LETO
      rats at age 50-53 weeks. Acetylcholine-, NS309-, and GSK1016790A-induced
      relaxations in arteries from OLETF rats were all significantly reduced compared
      to those in LETO rats. These results indicated that EDH-type relaxations were
      impaired in female OLETF rats. This novel experimental model may provide new
      insights into vascular dysfunction in metabolic syndrome in females.

PMID- 28433658
TI  - Molecular cloning of ESR2 and gene expression analysis of ESR1 and ESR2 in the
      pituitary gland of the Chinese alligator (Alligator sinensis) during female
      reproductive cycle.
AB  - Estrogens play critical roles in reproductive physiology via estrogen receptors
      (ESRs) in vertebrates, including reptiles. Chinese alligator (Alligator sinensis)
      is an endemic and endangered reptile species in China. In the present study, we
      cloned ESR2 gene from the ovary using rapid amplification of cDNA ends (RACE),
      investigated the spatial expression of ESRs in various tissues and temporal
      expression of ESRs in the pituitary glands during the reproductive cycle in
      Chinese alligators by quantitative real-time PCR (qPCR). Bioinformatics and
      phylogenetic analysis of deduced ESR2 protein were also performed. The full
      length cDNA of the ESR2 is 1647bp in length, with an open-reading frame encoding
      548 amino acids. The bioinformatics analysis indicated that the deduced amino
      acid sequence of alligator ESR2 was highly conserved with that of other
      vertebrate species. In addition, compared to human ESR2, the 14 amino acids in
      the alligator ESR2 that are essential for specific recognition of estradiol are
      entirely conserved. The phylogenetic analysis showed that alligators were more
      closely related to birds than to other reptiles. The results of qPCR showed that
      the tissue distribution patterns of both ESR subtype mRNAs appeared to be
      different. In male tissues, the highest mRNA level of both ESRs is in the liver.
      While in female tissues, ESR1 and ESR2 showed the highest mRNA level in the
      hypothalamus and pituitary gland, respectively. During the female reproductive
      cycle, the expression level of ESR1 mRNA increased from the initial post
      hibernation period to the reproductive period, reached its peak in the
      reproductive period, and then decreased in the autumn active period and
      hibernation period. Conversely, the highest transcription level of ESR2 was
      observed in the hibernation period.

PMID- 28433659
TI  - Carbonic anhydrase XII functions in health and disease.
AB  - Human CAXII was initially identified as a cancer marker in different cancers and
      tumors. Expression of CAXII is regulated by hypoxia and estrogen receptors. CAXII
      expression has been also detected in several tissues, whereas in cancer and tumor
      tissues its expression is several fold higher. In brain tumors, an alternatively
      spliced form of CAXII is expressed. Higher expression of CAXII in breast cancer
      is indicative of lower grade disease. CAXII plays a key role in several
      physiological functions. Mutation in the CAXII gene causes cystic fibrosis-like
      syndrome and salt wasting disease. CAXII is also seen in nuclear pulposus cells
      of the vertebrae. Aging dependent stiffness or degeneration of backbone
      correlates with CAXII expression level. This finding suggests a possible
      implication of CAXII as a biomarker for chronic back pain and a pharmacological
      target for possible treatment of chronic back pain.

PMID- 28433661
TI  - Differential protein acetylation assists import of excess SOD2 into mitochondria
      and mediates SOD2 aggregation associated with cardiac hypertrophy in the murine
      SOD2-tg heart.
AB  - SOD2 is the primary antioxidant enzyme neutralizing *O2- in mitochondria. Cardiac
      specific SOD2 overexpression (SOD2-tg) induces supernormal function and cardiac
      hypertrophy in the mouse heart. However, the reductive stress imposed by SOD2
      overexpression results in protein aggregation of SOD2 pentamers and differential
      hyperacetylation of SOD2 in the mitochondria and cytosol. Here, we studied SOD2
      acetylation in SOD2-tg and wild-type mouse hearts. LC-MS/MS analysis indicated
      the presence of four acetylated lysines in matrix SOD2 and nine acetylated
      lysines in cytosolic SOD2 from the SOD2-tg heart. However, only one specific
      acetylated lysine residue was detected in the mitochondria of the wild-type
      heart, which was consistent with Sirt3 downregulation in the SOD2-tg heart. LC
      MS/MS further detected hyperacetylated SOD2 with a signaling peptide in the
      mitochondrial inner membrane and matrix of the SOD2-tg heart, indicating partial
      arrest of the SOD2 precursor in the membrane during translocation into the
      mitochondria. Upregulation of HSP 70 and cytosolic HSP 60 enabled the
      translocation of excess SOD2 into mitochondria. In vitro acetylation of matrix
      SOD2 with Ac2O deaggregated pentameric SOD2, restored the profile of cytosolic
      SOD2 hyperacetylation, and decreased matrix SOD2 activity. As revealed by 3D
      structure, acetylation of K89, K134, and K154 of cytosolic SOD2 induces unfolding
      of the tertiary structure and breaking of the salt bridges that are important for
      the quaternary structure, suggesting that hyperacetylation and HSP 70
      upregulation maintain the unfolded status of SOD2 in the cytosol and mediate the
      import of SOD2 across the membrane. Downregulation of Sirt3, HSP 60, and
      presequence protease in the mitochondria of the SOD2-tg heart promoted protein
      misfolding that led to pentameric aggregation.

PMID- 28433662
TI  - Iron and thiol redox signaling in cancer: An exquisite balance to escape
      ferroptosis.
AB  - Epidemiological data indicate a constant worldwide increase in cancer mortality,
      although the age of onset is increasing. Recent accumulation of genomic data on
      human cancer via next-generation sequencing confirmed that cancer is a disease of
      genome alteration. In many cancers, the Nrf2 transcription system is activated
      via mutations either in Nrf2 or Keap1 ubiquitin ligase, leading to persistent
      activation of the genes with antioxidative functions. Furthermore, deep
      sequencing of passenger mutations is clarifying responsible cancer causative
      agent(s) in each case, including aging, APOBEC activation, smoking and UV.
      Therefore, it is most likely that oxidative stress is the principal initiating
      factor in carcinogenesis, with the involvement of two essential molecules for
      life, iron and oxygen. There is evidence based on epidemiological and animal
      studies that excess iron is a major risk for carcinogenesis, suggesting the
      importance of ferroptosis-resistance. Microscopic visualization of catalytic
      Fe(II) has recently become available. Although catalytic Fe(II) is largely
      present in lysosomes, proliferating cells harbor catalytic Fe(II) also in the
      cytosol and mitochondria. Oxidative stress catalyzed by Fe(II) is counteracted by
      thiol systems at different functional levels. Nitric oxide, carbon monoxide and
      hydrogen (per)sulfide modulate these reactions. Mitochondria generate not only
      energy but also heme/iron sulfur cluster cofactors and remain mostly
      dysfunctional in cancer cells, leading to Warburg effects. Cancer cells are under
      persistent oxidative stress with a delicate balance between catalytic iron and
      thiols, thereby escaping ferroptosis. Thus, high-dose L-ascorbate and non-thermal
      plasma as well as glucose/glutamine deprivation may provide additional benefits
      as cancer therapies over preexisting therapeutics.

PMID- 28433664
TI  - Ovaries of the white worm (Enchytraeus albidus, Annelida, Clitellata) are
      composed of 16-celled meroistic germ-line cysts.
AB  - The paired ovaries of E. albidus are like a bunch of grapes and are composed of
      clearly separated units, syncytial germ cysts (clusters), which are surrounded by
      a thin layer of somatic cells. Each cyst maintains the connection with the ovary
      by an extended stalk that is composed of somatic cells. The spatial architecture
      of the germ-line cysts found in E. albidus is the same as in other clitellate
      annelids that have been studied to date. As a rule, germ cells are located at the
      cyst periphery and each has only one ring canal that connects it to the common
      and centrally located cytoplasmic mass, the cytophore. Here we present data about
      the F-actin and microtubular cytoskeleton and some molecular components of the
      germ-line cysts. We show that the ring canals have an inner rim that is enriched
      with microfilaments and proteins that contain phosphotyrosine. The microtubules
      form a loose network in the cytoplasm of the oocyte and nurse cells; moreover,
      some of them pass through the ring canals to the cytophore. Numerous microtubules
      are also located in the somatic cells. The germ-line cysts in E. albidus ovaries
      consist of 16 cells, which is the lowest known number of interconnected germ
      cells within clitellate annelids. During oogenesis, the fate of interconnected
      germ cells differentiates and only one cell develops as the future egg, while the
      other 15 become nurse cells. This differentiation means ovary meroism. The nurse
      cells gather cell organelles and storage material that then pass through the ring
      canals and cytophore moving towards the growing oocyte. At the end of oogenesis,
      the vitellogenic oocyte surrounds the siblings' cells together with the cytophore
      and engulfs their remnants into the ooplasm. No morphological or molecular
      markers of the apoptosis of the nurse cells were found. Moreover, the nurse cells
      did not undergo polyploidisation. The measured DNA level was 4C, which indicates
      that these cells are not highly-specialised.

PMID- 28433663
TI  - Mitochondrial mechanisms of neuronal rescue by F-68, a hydrophilic Pluronic block
      co-polymer, following acute substrate deprivation.
AB  - Global brain ischemia can lead to widespread neuronal death and poor neurologic
      outcomes in patients. Despite detailed understanding of the cellular and
      molecular mechanisms mediating neuronal death following focal and global brain
      hypoxia-ischemia, treatments to reduce ischemia-induced brain injury remain
      elusive. One pathway central to neuronal death following global brain ischemia is
      mitochondrial dysfunction, one consequence of which is the cascade of
      intracellular events leading to mitochondrial outer membrane permeabilization. A
      novel approach to rescuing injured neurons from death involves targeting cellular
      membranes using a class of synthetic molecules called Pluronics. Pluronics are
      triblock copolymers of hydrophilic poly[ethylene oxide] (PEO) and hydrophobic
      poly[propylene oxide] (PPO). Evidence is accumulating to suggest that hydrophilic
      Pluronics rescue injured neurons from death following substrate deprivation by
      preventing mitochondrial dysfunction. Here, we will review current understanding
      of the nature of interaction of Pluronic molecules with biological membranes and
      the efficacy of F-68, an 80% hydrophilic Pluronic, in rescuing neurons from
      injury. We will review data indicating that F-68 reduces mitochondrial
      dysfunction and mitochondria-dependent death pathways in a model of neuronal
      injury in vitro, and present new evidence that F-68 acts directly on mitochondria
      to inhibit mitochondrial outer membrane permeabilization. Finally, we will
      present results of a pilot, proof-of-principle study suggesting that F-68 is
      effective in reducing hippocampal injury induced by transient global ischemia in
      vivo. By targeting mitochondrial dysfunction, F-68 and other Pluronic molecules
      constitute an exciting new approach to rescuing neurons from acute injury.

PMID- 28433665
TI  - Advancing the Science of Myocardial Recovery With Mechanical Circulatory Support:
      A Working Group of the National, Heart, Lung and Blood Institute.
AB  - The medical burden of heart failure (HF) has spurred interest in clinicians and
      scientists to develop therapies to restore the function of a failing heart. To
      advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI)
      convened a Working Group of experts on June 2-3, 2016, in Bethesda, Maryland, to
      develop recommendations for the NHLBI aimed at advancing the science of cardiac
      recovery in the setting of mechanical circulatory support (MCS). MSC devices
      effectively reduce volume and pressure overload that drives the cycle of
      progressive myocardial dysfunction, thereby triggering structural and functional
      reverse remodeling. Research in this field could be innovative in many ways, and
      the Working Group specifically discussed opportunities associated with genome
      phenome systems biology approaches, genetic epidemiology, bioinformatics and
      precision medicine at the population level, advanced imaging modalities including
      molecular and metabolic imaging, and developing minimally invasive surgical and
      percutaneous bioengineering approaches. These new avenues of investigations could
      lead to new treatments that target phylogenetically conserved pathways involved
      in cardiac reparative mechanisms. A central point that emerged from the NHLBI
      Working Group meeting was that the lessons learned from the MCS investigational
      setting can be extrapolated to the broader HF population. With the precedents set
      by the significant impact of studies of other well controlled and tractable
      subsets on larger populations, such as the genetic work in both cancer and
      cardiovascular disease, the work to improve our understanding of cardiac recovery
      and resilience in MCS patients could be transformational for the greater HF
      population.

PMID- 28433660
TI  - Redox regulation of gasotransmission in the vascular system: A focus on
      angiogenesis.
AB  - Reactive oxygen species have emerged as key participants in a broad range of
      physiological and pathophysiological processes, not least within the vascular
      system. Diverse cellular functions which have been attributed to some of these
      pro-oxidants within the vasculature include the regulation of blood pressure,
      neovascularisation and vascular inflammation. We here highlight the emerging
      roles of the enzymatically-generated reaction oxygen species, O2- and H2O2, in
      the regulation of the functions of the gaseous signalling molecules: nitric oxide
      (NO), carbon monoxide (CO), and hydrogen sulphide (H2S). These gasotransmitters
      are produced on demand from distinct enzymatic sources and in recent years it has
      become apparent that they are capable of mediating a number of homeostatic
      processes within the cardiovascular system including enhanced vasodilation,
      angiogenesis, wound healing and improved cardiac function following myocardial
      infarction. In common with O2- and/or H2O2 they signal by altering the functions
      of target proteins, either by the covalent modification of thiol groups or by
      direct binding to metal centres within metalloproteins, most notably haem
      proteins. The regulation of the enzymes which generate NO, CO and H2S have been
      shown to be influenced at both the transcriptional and post-translational levels
      by redox-dependent mechanisms, while the activity and bioavailability of the
      gasotransmitters themselves are also subject to oxidative modification. Within
      vascular cells, the family of nicotinamide adenine dinucleotide phosphate
      oxidases (NAPDH oxidases/Noxs) have emerged as functionally significant sources
      of regulated O2- and H2O2 production and accordingly, direct associations between
      Nox-generated oxidants and the functions of specific gasotransmitters are
      beginning to be identified. This review focuses on the current knowledge of the
      redox-dependent mechanisms which regulate the generation and activity of these
      gases, with particular reference to their roles in angiogenesis.

PMID- 28433666
TI  - Tricuspid Regurgitation in Heart Failure: No Longer Ignored.

PMID- 28433667
TI  - Cognitive Impairment and Heart Failure: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Cognitive impairment and dementia are associated with a range of
      cardiovascular conditions, including hypertension, coronary artery disease, and
      atrial fibrillation. We aimed to describe the association with heart failure,
      summarizing published data to give estimates of prevalence, incidence, and
      relative risk of cognitive impairment/dementia in heart failure. METHODS: We
      searched multidisciplinary databases including MEDLINE (OVID), EMBASE (OVID),
      CINAHL (EBSCO), PsychINFO (EBSCO), Web of Science (Thomson Reuters), and CENTRAL
      (Cochrane Library) from inception until May 31, 2015. All relevant studies
      looking at cognitive impairment/dementia in heart failure were included. Studies
      were selected by 2 independent reviewers using prespecified inclusion/exclusion
      criteria. Where data allowed, we performed meta-analysis and pooled results using
      random effects models. RESULTS: From 18,000 titles, 37 studies were eligible (n =
      8411 participants). Data from 4 prospective cohorts (n = 2513 participants)
      suggest greater cognitive decline in heart failure compared with non-heart
      failure over the longer term. These data were not suitable for meta-analysis. In
      case control studies describing those with and without heart failure (n = 4
      papers, 1414 participants) the odds ratio for cognitive impairment in the heart
      failure population was 1.67 (95% confidence interval 1.15-2.42). Prevalence of
      cognitive impairment in heart failure cohorts (n = 26 studies, 4176 participants)
      was 43% (95% confidence interval 30-55). CONCLUSIONS: This review suggests a
      substantial proportion of patients with heart failure have concomitant cognitive
      problems. This has implications for planning treatment and services. These data
      do not allow us to comment on causation, and further work is needed to describe
      the underlying pathophysiology.

PMID- 28433668
TI  - Deactivation of Ventricular Assist Devices: Perspectives and Experiences of Adult
      Cardiovascular Providers.

PMID- 28433669
TI  - Environmental enrichment reverses memory impairment induced by toluene in mice.
AB  - Toluene is the main component of a variety of inhalants that are used for
      intoxication purposes. Alterations in memory have been reported in inhalant
      users; however, it is unclear whether these impairments could be reversed, and
      the mechanisms involved in the putative recovery. Therefore, the main purpose of
      this study was to model the deleterious effects of toluene on memory in mice and
      to evaluate the effect of environmental enrichment on that response. In the
      second part of the study, the concentrations of glutamate and GABA, following
      chronic toluene exposure and after environmental enrichment treatment, were
      evaluated. Adolescent mice were exposed to either a single or repeated schedule
      of toluene administration and their responses to object recognition were
      analyzed. An independent group of mice was repeatedly exposed to toluene and then
      housed either under environmental enrichment or standard conditions for four
      weeks. At the end of the housing period, the rodents' performance in object
      recognition test, as well as the concentrations of neurotransmitters, were
      analyzed. The results showed that toluene caused memory impairment in mice that
      received a single or repeated solvent exposure. Remarkably, environmental
      enrichment could reverse memory deficits induced by repeated administration of
      toluene. Cessation of toluene exposure in mice in standard housing did not
      produce that response. The glutamate and GABA tissue contents were not involved
      in the effects of toluene or environmental enrichment of memory.

PMID- 28433670
TI  - Evaluation of the routine antimicrobial susceptibility testing results of
      clinically significant anaerobic bacteria in a Slovenian tertiary-care hospital
      in 2015.
AB  - The aim of our study was to determined antimicrobial susceptibility profiles of
      2673 clinically significant anaerobic bacteria belonging to the major genera,
      isolated in 2015 in a large tertiary-care hospital in Slovenia. The species
      identification was performed by MALDI-TOF mass spectrometry. Antimicrobial
      susceptibility was determined immediately at the isolation of the strains
      against: penicillin, co-amoxiclav, imipenem, clindamycin and metronidazole, using
      gradient diffusion methodology and EUCAST breakpoints. The most frequent
      anaerobes were Bacteroides fragilis group with 31% (n = 817), Gram positive
      anaerobic cocci (GPACs) with 22% (n = 589), Prevotella with 14% (n = 313) and
      Propionibacterium with 8% (n = 225). Metronidazole has retained full activity
      (100%) against all groups of anaerobic bacteria intrinsically susceptible to it.
      Co-amoxiclav and imipenem were active against most tested anaerobes with zero or
      low resistance rates. However, observed resistance to co-amoxiclav (8%) and
      imipenem (1%) is worrying especially among B. fragilis group isolates. High
      overall resistance (23%) to clindamycin was detected in our study and was highest
      among the genera Prevotella, Bacteroides, Parabacteroides, GPACs and Clostridium.
      Routine testing of antimicrobial susceptibility of clinically relevant anaerobic
      bacteria is feasible and provides good surveillance data.

PMID- 28433671
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Paper 3: patient
      reported outcomes can facilitate shared decision-making and guide self
      management.
AB  - BACKGROUND: There is a shift toward making health care patient centered, whereby
      patients are part of medical decision-making and take responsibility for managing
      their health. Patient-reported outcomes (PROs) capture the patient voice and can
      be used to engage patients in medical decision-making. OBJECTIVE: The objective
      of this paper is to present important factors from patients', clinicians',
      researchers', and decision-makers' perspectives that influence successful
      adoption of PROs in clinical practice. Factors recommended in this paper were
      informed by a patient partner. DISCUSSION: Based on themes arising from the
      Montreal Accord proceedings, we describe factors that influence the adoption of
      PROs and how PROs can have a positive effect by enhancing communication and
      providing opportunities to engage patients, carers, and clinicians in care.
      Consideration of patient factors (e.g., health literacy), family support and
      networks (e.g., peer-support networks), technology (e.g., e-health), and health
      care system factors (e.g., resources to implement PROs) is necessary to ensure
      PROs are successfully adopted. PRO evaluation plans most likely to succeed over
      the long term are those incorporating PROs identified by patients as necessary
      for self-management and that coincide with providers' needs for collaboratively
      developing treatment plans with patients and families.

PMID- 28433672
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Paper 1:
      introduction.
AB  - BACKGROUND: Patient-centered health care, where we design and deliver care to
      address the needs and preferences of patients, represents an important paradigm
      shift. Patient-reported outcomes (PROs) are critical to capture the patient
      voice, understand how illness and treatments affect people, and establish how
      well services and treatments address what matters most to patients. OBJECTIVE:
      Originally developed for use in research, PROs are now used to monitor
      individuals and populations, manage care, evaluate services and providers, and
      inform policy. However, moving PROs beyond research settings incurs considerable
      methodological, organizational, technological, and ethical considerations.
      National collaborative networks of researchers, clinicians, patients, and other
      stakeholders can address these challenges by coordinating development, creating
      standards for use, sharing costs and delivery platforms, and improving widespread
      uptake of core sets of measures to better inform health care decisions and
      improve outcomes. DISCUSSION: We introduce eight papers from researchers,
      clinicians, patients, and decision makers who participated in deliberations
      around creating a national network to accelerate the application and harmonized
      use of PROs in Canada. They offer a snap shot of the strategies that pioneers and
      innovative thinkers are using to integrate the patient voice into comprehensive
      care, research, and health policy planning of chronic diseases.

PMID- 28433673
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Paper 2:
      terminology proposed to measure what matters in health.
AB  - BACKGROUND: We outline different health outcomes and describe how multiple
      perspectives can be harnessed to optimize accuracy of key data collected about
      patients with chronic conditions. The terms health status, health-related quality
      of life, and quality of life are often used interchangeably without recognizing
      that they have different meanings, as are the terms used to refer to the
      different components of function. Although the advantages and limitations of
      existing frameworks and perspectives are largely understood, greater precision is
      needed when using health outcome terminology and identifying optimal sources of
      information. OBJECTIVE: A refinement of the current taxonomy is proposed to
      distinguish between patient-reported outcomes and self-report outcomes and expand
      the concept of clinically reported outcomes to include those assessed by
      performance and emerging technologies. DISCUSSION: Health outcomes yield
      important information that can be used to improve the lives of many people. Now
      is the time to "talk the talk" as part of larger coordinated efforts within and
      across countries to identify and measure what matters most in health.

PMID- 28433674
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Paper 6:
      creating national initiatives to support development and use-the PROMIS example.
AB  - BACKGROUND: Patient-reported outcome (PRO) data are beneficial to a range of
      stakeholders including patients, clinicians, researchers, national funding and
      regulatory agencies, health system administrators, and policymakers. OBJECTIVE:
      Because stakeholders represent diverse groups and needs, it is challenging to
      reach consensus on how to advance PRO development and harmonize data across
      settings to enable use for multiple secondary purposes. Collaborative national
      networks can facilitate the sharing of expertise, resources, and necessary
      infrastructure; create development, use, and reporting standards; optimize
      formats to efficiently store and transfer data; and disseminate tools and
      information for widespread uptake. DISCUSSION: In the United States, the National
      Institutes of Health's Patient-Reported Outcomes Measurement Information System
      offers an example of how collaborators can work across distances to form
      essential partnerships, create a common vision, and leverage technology to
      accelerate the development and testing of universal PROs that are broadly
      applicable across health conditions and settings.

PMID- 28433675
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Paper 8: patient
      reported outcomes in electronic health records can inform clinical and policy
      decisions.
AB  - BACKGROUND: Given that the goal of health care systems is to improve and maintain
      the health of the populations they serve, the indicators of performance must
      include outcomes that are meaningful to patients. The growth of health
      technologies provides an unprecedented opportunity to integrate the patient voice
      into clinical care by linking electronic health records (EHRs) to patient
      reported outcome (PRO) data collection. However, PRO data must be relevant,
      meaningful, and actionable for those who will have to invest the time and effort
      to collect it. OBJECTIVE: In this study, we highlight opportunities to integrate
      PRO data collection into EHRs. We consider how stakeholder perspectives should
      influence the selection of PROs and ways to enhance engagement in and commitment
      to PRO implementation. We propose a research and policy agenda to address
      unanswered questions and facilitate the widespread adoption of PRO data
      collection into EHRs. DISCUSSION: Building a learning health care system that
      gathers PRO data in ways that can inform individual patient care, quality
      improvement, and comparative effectiveness research has the potential to
      accelerate the application of new evidence and knowledge to patient care.

PMID- 28433676
TI  - Further exploration of dissemination bias in qualitative research required to
      facilitate assessment within qualitative evidence syntheses.
AB  - OBJECTIVES: To conceptualise and discuss dissemination bias in qualitative
      research. RESULTS: It is likely that the mechanisms leading to dissemination bias
      in quantitative research, including time lag, language, gray literature, and
      truncation bias also contribute to dissemination bias in qualitative research.
      These conceptual considerations have informed the development of a research
      agenda. CONCLUSION: Further exploration of dissemination bias in qualitative
      research is needed, including the extent of non-dissemination and related
      dissemination bias, and how to assess dissemination bias within qualitative
      evidence syntheses. We also need to consider the mechanisms through which
      dissemination bias in qualitative research could occur to explore approaches for
      reducing it.

PMID- 28433677
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Paper 9:
      anonymization and ethics considerations for capturing and sharing patient
      reported outcomes.
AB  - BACKGROUND: Patient-reported outcomes (PROs) are collected with consent for care;
      however, using the data for any other purpose requires consent for that
      additional purpose, or the anonymization of the data. Collecting explicit consent
      to use this data for secondary purposes, before the patient completes a PRO, can
      also bias the responses. OBJECTIVE: We consider the ethical and security issues
      related to the collection of data at the point of care or in the population and
      the aggregation and integration of PRO data with administrative databases to
      facilitate decision making and comparative effectiveness research. DISCUSSION: In
      this article, we describe risk-based anonymization, taking the context of the
      data release into account, so that we may consider the degree by which the
      release is considered anonymized. We also consider the ethical use of anonymized
      data, the anonymization of free-form text, and the secure linking data sets
      without sharing any personal information. Many good standards and best practices
      exist for the sharing of health data and could be used as a baseline in the
      development of a national PRO initiative.

PMID- 28433678
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Paper 4: patient
      reported outcomes can inform clinical decision making in chronic care.
AB  - BACKGROUND: Providing patient-centered health care requires that patient needs,
      preferences, and valued outcomes are more fully integrated into all decisions.
      Patient-reported outcome (PRO) measures provide unique information from the
      patient perspective on overall health, symptoms, burden, and treatment response.
      OBJECTIVE: We sought to describe applications of PROs in clinical settings and
      considerations for implementation from the perspectives of PRO researchers,
      clinicians, administrators, policy makers, and patients attending a
      multidisciplinary meeting. DISCUSSION: Clinical applications of PROs include
      individual level use for medical decision making and aggregate use for
      comparative effectiveness research, program evaluation, quality improvement, and
      performance assessments. Considerations of feasibility on workflow impact and
      patient burden, display of results, and administration frequency are important.
      PROs with strong psychometric properties, actionable thresholds, and
      interpretable results should be selected. We provide current exemplars of PRO use
      in various clinical applications, initial lessons learned, and highlight
      conceptual, logistical, and consequential considerations of PRO data collection.
      A research agenda is proposed to address critical knowledge gaps. In conclusion,
      PROs can be used in clinical settings to support patient-centered care. This
      requires an assessment of feasibility in the intended setting of use, measurement
      considerations, and process measures to optimize integration and use.

PMID- 28433679
TI  - Part I: Design, synthesis and biological evaluation of novel pyrazole
      benzimidazole conjugates as checkpoint kinase 2 (Chk2) inhibitors with studying
      their activities alone and in combination with genotoxic drugs.
AB  - Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main
      enzymes that affect the cell cycle. 2-Biarylbenzimidazoles are potent selective
      class of Chk2 inhibitors; the structure-based design was applied to synthesize a
      new series of this class with replacing the lateral aryl group by substituted
      pyrazoles. Ten pyrazole-benzimidazole conjugates from the best fifty candidates
      according to docking programs have been subjected to chemical synthesis in this
      study. The activities of the conjugates 5-14 as checkpoint kinase inhibitors and
      as antitumor alone and in combination with genotoxic drugs were evaluated. The
      effect of compounds 7 and 12 on cell-cycle phases was analyzed by flow cytometry
      analysis. Antitumor activity of compounds 7 and 12 as single-agents and in
      combinations with doxorubicin was assessed in breast cancer bearing animals
      induced by MNU. The Results indicated that compounds 5-14 inhibited Chk2 activity
      with high potency (IC50 52.8 nM-5.5 nM). The cytotoxicity of both cisplatin and
      doxorubicin were significantly potentiated by the most of the conjugates against
      MCF-7 cell lines. Compounds 7 and 12 and their combinations with doxorubicin
      induced the cell cycle arrest in MCF-7 cells. Moreover, compound 7 exhibited
      marked higher antitumor activity as a single agent in animals than it's
      combination with doxorubicin or doxorubicin alone. The combination of compound 12
      with doxorubicin was greatly effective on animal than their single-dose
      treatment. In conclusion, pyrazole-benzimidazole conjugates are highly active
      Chk2 inhibitors that have anticancer activity and potentiate activity of
      genotoxic anticancer therapies and deserve further evaluations.

PMID- 28433680
TI  - Organocatalyzed and mechanochemical solvent-free synthesis of novel and
      functionalized bis-biphenyl substituted thiazolidinones as potent tyrosinase
      inhibitors: SAR and molecular modeling studies.
AB  - Eluding the involvement of solvents in organic synthesis and introducing
      environment friendly procedures can control environmental problems. A facile and
      an efficient solvent free mechanochemical method (grinding) is achieved to
      synthesize novel bis-biphenyl substituted thiazolidinones using non-toxic and
      cheap N-acetyl glycine (NAG). Organocatalytic condensation of a series of
      Schiff's bases bearing different substituents with thioglycolic acid produces a
      variety of thiazolidinones derivatives in good to excellent yield. In vitro
      inhibition studies against mushroom tyrosinase of these thiazolidinone analogues
      revealed that many of them possessed good to excellent tyrosinase inhibition at
      low micro-molar concentrations. In particular, six compounds exhibited potent
      inhibitory potential with IC50 values ranging from 0.61 +/- 0.31 to 21.61 +/-
      0.11 MUM as compared with that of standard kojic acid (IC50 6.04 +/- 0.11 MUM).
      Further molecular docking studies revealed that the thiazolidinones moiety plays
      a key role in the inhibition mechanism by well fitting into the enzyme bounding
      pocket.

PMID- 28433681
TI  - N-Aryl-N'-ethyleneaminothioureas effectively inhibit acetylcholinesterase 1 from
      disease-transmitting mosquitoes.
AB  - Vector control of disease-transmitting mosquitoes by insecticides has a central
      role in reducing the number of parasitic- and viral infection cases. The
      currently used insecticides are efficient, but safety concerns and the
      development of insecticide-resistant mosquito strains warrant the search for
      alternative compound classes for vector control. Here, we have designed and
      synthesized thiourea-based compounds as non-covalent inhibitors of
      acetylcholinesterase 1 (AChE1) from the mosquitoes Anopheles gambiae (An.
      gambiae) and Aedes aegypti (Ae. aegypti), as well as a naturally occurring
      resistant-conferring mutant. The N-aryl-N'-ethyleneaminothioureas proved to be
      inhibitors of AChE1; the most efficient one showed submicromolar potency.
      Importantly, the inhibitors exhibited selectivity over the human AChE (hAChE),
      which is desirable for new insecticides. The structure-activity relationship
      (SAR) analysis of the thioureas revealed that small changes in the chemical
      structure had a large effect on inhibition capacity. The thioureas showed to have
      different SAR when inhibiting AChE1 and hAChE, respectively, enabling an
      investigation of structure-selectivity relationships. Furthermore, insecticidal
      activity was demonstrated using adult and larvae An. gambiae and Ae. aegypti
      mosquitoes.

PMID- 28433682
TI  - A mechanistic review on vermifiltration of wastewater: Design, operation and
      performance.
AB  - With global population explosion, the available water resources are slowly being
      polluted due to the excessive human interference. To encounter this, it is the
      need of this hour to find out sustainable pollution remediating technologies to
      meet the stringent discharge standards for domestic as well as industrial
      wastewaters. In addition, those techniques should have the capabilities for
      effective implementation even in developing countries. Based on the available
      literatures, one such technique, named vermifilter, has been identified which
      takes care of almost all the sustainable and economical criteria for its
      effective implementation even in developing countries. The aim of this meta
      analysis is to provide a comprehensive review on assessment mechanisms involved,
      factors affecting the process and performance of vermifiltration under different
      scenarios. The present review envisages the current state of the knowledge
      regarding physical, chemical and biological aspects related to the treatment
      mechanisms and effective functioning of earthworms. This review has also proposed
      several suggestive plans on its application at any proposed site.

PMID- 28433683
TI  - Municipal wastewater sludge as a sustainable bioresource in the United States.
AB  - Within the United States and Puerto Rico, publicly owned treatment works (POTWs)
      process 130.5 Gl/d (34.5 Bgal/d) of wastewater, producing sludge as a waste
      product. Emerging technologies offer novel waste-to-energy pathways through whole
      sludge conversion into biofuels. Assessing the feasibility, scalability and
      tradeoffs of various energy conversion pathways is difficult in the absence of
      highly spatially resolved estimates of sludge production. In this study, average
      wastewater solids concentrations and removal rates, and site specific daily
      average influent flow are used to estimate site specific annual sludge production
      on a dry weight basis for >15,000 POTWs. Current beneficial uses, regional
      production hotspots and feedstock aggregation potential are also assessed.
      Analyses indicate 1) POTWs capture 12.56 Tg/y (13.84 MT/y) of dry solids; 2) 50%
      are not beneficially utilized, and 3) POTWs can support seven regions that
      aggregate >910 Mg/d (1000 T/d) of sludge within a travel distance of 100 km.

PMID- 28433684
TI  - Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER
      stress-mediated liver injury.
AB  - Endoplasmic reticulum (ER) stress is characterized by an accumulation of
      misfolded proteins, and ER stress reduction is essential for maintaining tissue
      homeostasis. However, the molecular mechanisms that protect cells from ER stress
      are not completely understood. The present study investigated the role of sestrin
      2 (SESN2) on ER stress and sought to elucidate the mechanism responsible for the
      hepatoprotective effect of SESN2 in vitro and in vivo. Treatment with tunicamycin
      (Tm) increased SESN2 protein and mRNA levels and reporter gene activity.
      Activating transcription factor 6 (ATF6) bound to unfolded protein response
      elements of SESN2 promoter, transactivated SESN2, and increased SESN2 protein
      expression. In addition, dominant negative mutant of ATF6alpha and siRNA against
      ATF6alpha blocked the ER stress-mediated SESN2 induction, whereas chemical
      inhibition of PERK or IRE1 did not affect SESN2 induction by Tm. Ectopic
      expression of SESN2 in HepG2 cells inhibited CHOP and GRP78 expressions by Tm.
      Moreover, SESN2 decreased the phosphorylations of JNK and p38 and PARP cleavage,
      and blocked the cytotoxic effect of excessive ER stress. In a Tm-induced liver
      injury model, adenoviral delivery of SESN2 in mice decreased serum ALT, AST and
      LDH activities and the mRNA levels of CHOP and GRP78 in hepatic tissues.
      Moreover, SESN2 reduced numbers of degenerating hepatocytes, and inhibited
      caspase 3 and PARP cleavages. These results suggest ATF6 is essential for ER
      stress-mediated SESN2 induction, and that SESN2 acts as a feedback regulator to
      protect liver from excess ER stress.

PMID- 28433685
TI  - p62-Mediated mitochondrial clustering attenuates apoptosis induced by
      mitochondrial depolarization.
AB  - Parkin/PINK1-mediated mitophagy is implicated in the pathogenesis of Parkinson's
      disease (PD). Prior to elimination of damaged mitochondria, Parkin translocates
      to mitochondria and induces mitochondrial clustering. While the mechanism of
      PINK1-dependent Parkin redistribution to mitochondria is now becoming clear, the
      role of mitochondrial clustering has been less well understood. In our study, we
      found that loss of p62 disrupted mitochondrial aggregation and specifically
      sensitized Parkin-expressing cells to apoptosis induced by mitochondrial
      depolarization. Notably, altering mitochondrial aggregation through regulating
      p62 or other methods was sufficient to affect such apoptosis. Moreover,
      disruption of mitochondrial aggregation promoted proteasome-dependent degradation
      of outer mitochondrial membrane (OMM) proteins. The accelerated degradation in
      turn facilitated cytochrome c release from mitochondria, leading to apoptosis.
      Together, our study demonstrates a protective role of mitochondrial clustering in
      mitophagy and helps in understanding how aggregation defends cells against
      stress.

PMID- 28433686
TI  - Mitochatting - If only we could be a fly on the cell wall.
AB  - Mitochondria, cellular metabolic hubs, perform many essential processes and are
      required for the production of metabolites such as ATP, iron-sulfur clusters,
      heme, amino acids and nucleotides. To fulfill their multiple roles, mitochondria
      must communicate with all other organelles to exchange small molecules, ions and
      lipids. Since mitochondria are largely excluded from vesicular trafficking
      routes, they heavily rely on membrane contact sites. Contact sites are areas of
      close proximity between organelles that allow efficient transfer of molecules,
      saving the need for slow and untargeted diffusion through the cytosol. More
      globally, multiple metabolic pathways require coordination between mitochondria
      and additional organelles and mitochondrial activity affects all other cellular
      entities and vice versa. Therefore, uncovering the different means of
      mitochondrial communication will allow us a better understanding of mitochondria
      and may illuminate disease processes that occur in the absence of proper cross
      talk. In this review we focus on how mitochondria interact with all other
      organelles and emphasize how this communication is essential for mitochondrial
      and cellular homeostasis. This article is part of a Special Issue entitled:
      Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.

PMID- 28433688
TI  - Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3
      innate lymphoid cells.
AB  - BACKGROUND: Vitamin D deficiency is a risk factor for inflammatory bowel disease
      (IBD). The IL-23-driven tissue-resident group 3 innate lymphoid cells (ILC3s)
      play essential roles in intestinal immunity, and targeting IL-23/12 is a
      promising approach in IBD therapy. OBJECTIVE: We set out to define the role of
      1alpha,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of
      human mucosal ILC3s to IL-23 plus IL-1beta stimulation. METHODS: Transcriptomes
      of sorted tonsillar ILC3s were assessed by using microarray analysis. ILC3
      cytokine production, proliferation, and differentiation were determined by means
      of flow cytometry, ELISA, and multiplex immunoassay. Intestinal cell suspensions
      and ILC3s sorted from gut biopsy specimens of patients with IBD were also
      analyzed along with plasma 25-hydroxy vitamin D3 (25D) detection. RESULTS: ILC3s
      stimulated with IL-23 plus IL-1beta upregulated the vitamin D receptor and
      responded to 1,25D with downregulation of the IL-23 receptor pathway.
      Consequently, 1,25D suppressed IL-22, IL-17F, and GM-CSF production from
      tonsillar and gut ILC3s. In parallel, 1,25D upregulated genes linked to the IL
      1beta signaling pathway, as well as the IL-1beta-inducible cytokines IL-6, IL-8,
      and macrophage inflammatory protein 1alpha/beta. The 1,25D-triggered skewing in
      ILC3 function was not accompanied or caused by changes in viability,
      proliferation, or phenotype. Finally, we confirmed low 25D plasma levels in
      patients with IBD with active inflammation. CONCLUSION: In light of the
      beneficial targeting of IL-23/12 in patients with IBD, 1,25D appears as an
      interesting therapeutic agent that inhibits the IL-23 receptor pathway, providing
      a novel mechanism for how ILC3s could be manipulated to regulate intestinal
      inflammation.

PMID- 28433687
TI  - Steroid resistance of airway type 2 innate lymphoid cells from patients with
      severe asthma: The role of thymic stromal lymphopoietin.
AB  - BACKGROUND: Type 2 innate lymphoid cells (ILC2s) represent an important type 2
      immune cell. Glucocorticoid regulation of human ILC2s is largely unknown.
      OBJECTIVE: We sought to assess steroid resistance of human blood and airway ILC2s
      from asthmatic patients and to examine its mechanism of induction. METHODS: We
      studied human blood and lung ILC2s from asthmatic patients and control subjects
      using flow cytometry and ELISA. RESULTS: Dexamethasone inhibited (P = .04)
      chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes and
      type 2 cytokine expression by blood ILC2s stimulated with IL-25 and IL-33.
      However, it did not do so when ILC2s were stimulated with IL-7 and thymic stromal
      lymphopoietin (TSLP), 2 ligands of IL-7 receptor alpha. Unlike blood ILC2s,
      bronchoalveolar lavage (BAL) fluid ILC2s from asthmatic patients were resistant
      to dexamethasone. BAL fluid from asthmatic patients had increased TSLP but not IL
      7 levels. BAL fluid TSLP levels correlated (r = 0.74) with steroid resistance of
      ILC2s. TSLP was synergistically induced in epithelial cells by IL-13 and human
      rhinovirus. Mechanistically, dexamethasone upregulated ILC2 expression of IL-7
      receptor alpha, which augmented and sustained signal transducer and activator of
      transcription (STAT) 5 signaling by TSLP. TSLP induced mitogen-activated protein
      kinase kinase (MEK), c-Fos, inhibitor of DNA binding 3, phosphorylated signal
      transducer and activator of transcription (pSTAT) 3, and pSTAT5, molecules linked
      to steroid resistance. Dexamethasone inhibited c-Fos, inhibitor of DNA binding 3,
      and pSTAT3 but not pSTAT5 and MEK. The MEK inhibitor trametinib, the Janus kinase
      STAT inhibitor tofacitinib, and the STAT5 inhibitor pimozide reversed steroid
      resistance of BAL ILC2s. CONCLUSIONS: Dexamethasone inhibited type 2 cytokine
      production by blood ILC2s. IL-7 and TSLP abrogated this inhibition and induced
      steroid resistance of ILC2s in a MEK- and STAT5-dependent manner. BAL fluid ILC2s
      from asthmatic patients with increased TSLP levels were steroid resistant, which
      was reversed by clinically available inhibitors of MEK and STAT5.

PMID- 28433689
TI  - Type 3 innate lymphoid cells induce proliferation of CD94+ natural killer cells.

PMID- 28433690
TI  - Asthma: The past, future, environment, and costs.

PMID- 28433691
TI  - Direct monitoring of basophil degranulation by using avidin-based probes.

PMID- 28433692
TI  - Enhanced Biological Phosphorus Removal at low Sludge Retention Time in view of
      its integration in A-stage systems.
AB  - The two-stage A/B WWTP configuration is being studied as a possible wastewater
      treatment with low energy consumption or even with a net energy generation. The
      first phase, A-stage, is designed to remove organic matter at very short Sludge
      Retention Time (SRT), while the B-stage is based on autotrophic nitrogen removal.
      However, P-removal in the A/B process usually only relies on precipitation. This
      work studies the potential inclusion of Enhanced Biological Phosphorus Removal
      (EBPR) in the A-stage phase. For this aim, the long-term operation of three
      different Sequencing Batch Reactors (SBR) enriched in Accumulibacter at low SRT
      was thoroughly monitored for more than three months each one. This work shows
      that EBPR can be sustained with a minimal SRT of 3.6 d at 25  degrees C. Lower
      values, SRT = 3 d, led to the PAO washout because of a reduction in P-release and
      P-uptake, an increase of the VSS/TSS ratio and a decrease of the P/C ratio. The
      Yobs could be related to the SRT with the parameters Y = 0.39 +/- 0.05 gCODX.g
      1CODS and kD = 0.06 +/- 0.04 d-1 which leads to a 24% increase of biomass yield
      when SRT was reduced from 10 to 4 d.

PMID- 28433693
TI  - Cyanotoxins: Which detection technique for an optimum risk assessment?
AB  - The presence of toxigenic cyanobacteria (blue-green algae) in drinking water
      reservoirs poses a risk to human and animal health worldwide. Guidelines and
      health alert levels have been issued in the Australian Drinking Water Guidelines
      for three major toxins, which are therefore the subject of routine monitoring:
      microcystin, cylindrospermopsin and saxitoxin. While it is agreed that these
      toxic compounds should be monitored closely, the routine surveillance of these
      bioactive chemicals can be done in various ways and deciding which technique to
      use can therefore be challenging. This study compared several assays available
      for the detection of these toxins and their producers in environmental samples:
      microscopy (for identification and enumeration of cyanobacteria), ELISA (Enzyme
      Linked ImmunoSorbant Assay), PPIA (Protein phosphatase inhibition assay), PSI
      (Protein synthesis inhibition), chemical analysis and PCR (Polymerase Chain
      Reaction). Results showed that there was generally a good correlation between the
      presence of potentially toxigenic cyanobacteria and the detection of the toxin by
      ELISA. Nevertheless data suggest that cell numbers and toxin concentrations
      measured in bioassays do not necessarily correlate and that enumeration of
      potentially toxic cyanobacteria by microscopy, while commonly used for monitoring
      and risk assessment, is not the best indicator of real toxin exposure. The
      concentrations of saxitoxins quantified by ELISA were significantly different
      than those measured by LC-MS, while results were comparable in both assays for
      microcystin and cylindrospermopsin. The evaluation of these analytical methods
      led to the conclusion that there is no "gold standard" technique for the
      detection of the aforementioned cyanotoxins but that the choice of detection
      assay depends on cost, practicality, reliability and comparability of results and
      essentially on the question to be answered, notably on toxin exposure potential.

PMID- 28433694
TI  - Bacteroidales markers for microbial source tracking in Southeast Asia.
AB  - The island city country of Singapore served as a model to validate the use of
      host-associated Bacteroidales 16S rRNA gene marker assays for identifying sources
      of fecal pollution in the urban tropical environment of Southeast Asia. A total
      of 295 samples were collected from sewage, humans, domesticated animals (cats,
      dogs, rabbits and chicken), and wild animals (birds, monkeys and wild boars).
      Samples were analyzed by real time PCR using five human-associated assays (HF183
      SYBR Green, HF183, BacHum, BacH and B. thetaiotaomicron alpha-1-6, mannanase (B.
      theta), one canine-associated assay (BacCan), and a total Bacteroidales assay
      (BacUni). The best performing human-associated assay was B. theta with a
      diagnostic sensitivity of 69% and 100% in human stool and sewage, respectively,
      and a specificity of 98%. BacHum achieved the second highest sensitivity and
      specificity for human stool at 65% and 91%, respectively. The canine-associated
      Bacteroidales assay (BacCan) had a sensitivity and specificity above 80% and was
      validated for tracking fecal pollution from dogs. BacUni demonstrated a
      sensitivity and specificity of 100% for mammals, thus BacUni was confirmed for
      total Bacteroidales detection in the region. We showed for the first time that
      rabbit fecal samples cross-react with human-associated assays (HF183-SYBR Green,
      HF183, BacHum and BacH) and with BacCan. Our findings regarding the best
      performing human-associated assays differ from those reported in Bangladesh and
      India, which are geographically close to Southeast Asia, and where HF183 and
      BacHum were the preferred assays, respectively.

PMID- 28433695
TI  - Disinfection of water inoculated with Enterococcus faecalis using
      solar/Fe(III)EDDS-H2O2 or S2O82- process.
AB  - In this study, the activation of H2O2 and persulfate ions induced by solar
      photolysis of Fe(III)EDDS complex were investigated in water disinfection,
      applying solar AOPs processes. The use of Fe(III)EDDS complex maintains iron in
      soluble form until slightly basic pH and so the photolysis is efficient in a
      large range of pH compatible with natural waters. Moreover, for the first time,
      the impact of photogenerated hydroxyl and sulfate radicals on the inactivation of
      Enterococcus faecalis in water was studied. E. faecalis was proposed as
      alternative model microorganism given its higher resistance than the commonly
      used E. coli. The reactivity of hydroxyl radicals seems to be more efficient for
      the inactivation of such strain than the reactivity of sulfate radicals.
      Moreover, experimental results show that the concentration of Fe(III)EDDS complex
      is a key parameter for the inactivation of microrganisms. For the direct
      application in natural waters, the efficiency of the process in the presence of
      ubiquitous inorganic compounds, such as carbonate (HCO3-/CO32-) and chloride ions
      (Cl-), was also investigated. Carbonates showed a strong reduction on the E.
      faecalis inactivation in all cases; meanwhile chloride ions enhanced the
      inactivation in the presence of persulfate as also shown by using a complementary
      kinetic modeling approach. A dual role of Fe(III)EDDS complex was established and
      discussed; essential for the generation of radical species but a trap for the
      reactivity of these same radicals.

PMID- 28433696
TI  - FOXC2 positively regulates YAP signaling and promotes the glycolysis of
      nasopharyngeal carcinoma.
AB  - YAP signaling has been reported to be dysregulated in numerous cancer types.
      However, its roles in nasopharyngeal carcinoma (NPC) are poorly understood.
      Although several studies have shown that FOXC2 promotes the progression of NPC,
      the underlying molecular mechanism remains largely unknown. Here, we have shown
      that FOXC2 interacted with YAP and TEAD, and activated YAP signaling.
      Furthermore, FOXC2-YAP signaling positively regulated the expression of
      Hexokinase 2 (HK2) and promoted the glycolysis. Moreover, the inhibitor of HK2, 3
      BrPA effectively inhibited the tumorigenesis of NPC cells in vitro and in vivo.
      Collectively, our study demonstrated that FOXC2 promoted the glycolysis in
      progression of NPC by activating YAP signaling, and suggested that FOXC2 might be
      promising therapeutic target.

PMID- 28433697
TI  - Rab22a enhances CD147 recycling and is required for lung cancer cell migration
      and invasion.
AB  - Rab22a is a member of the Ras-related small GTPase family, which plays a key role
      in regulating the recycling of cargo proteins entering cells through clathrin
      independent endocytosis (CIE). Rab22a is overexpressed in different cancer types,
      including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma.
      However, its oncogenic role remains unknown. In this study, we found that
      silencing of Rab22a suppressed the migration and invasion of lung cancer cells.
      Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147
      recycling and promotes CD147 degradation. Taken together, our findings indicate
      that Rab22a enhances recycling of CD147, which is required for lung cancer cell
      migration and invasion,and targeting CD147 recycling may be a rational strategy
      for lung cancer therapy.

PMID- 28433698
TI  - Adipose crosstalk with other cell types in health and disease.
AB  - In addition to storing and mobilizing energy, adipocytes secrete circulating
      factors to signal to other tissues and coordinate energy metabolism. These
      functions can become disrupted in the setting of obesity, contributing to the
      development of diabetes, cardiovascular disease, and cancer. Since the discovery
      of leptin and adiponectin, an increasing number of adipokines have been
      identified and their functions elucidated. More recent studies have highlighted
      other modes by which adipose tissue can participate in crosstalk with other cell
      types and tissues. These modes of communication, which are reviewed here, include
      the secretion of enzymes, lipid species, and exosomes. Advances in profiling
      technology suggest that a substantial number of adipose-derived factors remain to
      be characterized. Further advances in this growing field are likely to provide
      important basic insights into the molecular control of metabolism.

PMID- 28433700
TI  - Isotopic characterization and thermal neutron flux determination of a PuBe
      neutron source.
AB  - The Indian Institute of Technology Kanpur (IIT Kanpur) possesses a PuBe neutron
      source facility with an initial activity of 5 Ci, dated September 1966 (nearly 50
      years ago). An understanding of the present activity and the rate of its change
      will allow implementation of proper radiological safety procedures and future
      radiological safety planning. Knowing the absolute neutron flux will help us in
      future neutron activation studies. These details are also important to ensure
      proper security precautions. In our work, we attempt to identify the isotopic
      composition to determine the rate of change of the source and the absolute
      thermal neutron flux of plutonium beryllium (PuBe) sample at IIT Kanpur. We have
      used gamma-ray spectroscopy for determining the isotopic composition of the PuBe
      neutron source. After utilizing gamma-ray spectroscopy it is found that the
      source is composed of 239Pu and a small amount of 241Am is present as an
      impurity. The mass ratio of 241Am to 239Pu is found to be approximately 18.1ug/g
      with an uncertainty of 1.39%. Delayed gamma neutron activation analysis (DGNAA)
      is used to determine the thermal neutron flux of the same PuBe neutron source
      using copper, cobalt, nickel and cadmium samples. The average thermal neutron
      flux as calculated from DGNAA is approximately 1.27*103n/(cm2-s) at 1cm above the
      PuBe neutron source.

PMID- 28433699
TI  - EGFR-mediated apoptosis via STAT3.
AB  - The Epidermal Growth Factor Receptor (EGFR) is a cell surface receptor with
      primary implications in cell growth in both normal and malignant tissue.
      Paradoxically, cell lines that hyperexpress the EGFR have been documented to
      undergo receptor-mediated apoptosis. The underlying mechanism by which EGF
      induced apoptosis occurs however remains inexplicit. In an attempt to identify
      this mechanism, we assessed downstream effectors of EGFR in MDA-MB-468 cells
      during conditions of EGF-induced apoptosis. The effector assessment revealed
      STAT3 as a potential mediator of EGF-induced apoptosis. Alternative strategies
      for activating STAT3, independent of EGFR stimulation, resulted in the induction
      of the apoptotic pathways. A reduction in STAT3 expression via RNAi resulted in a
      significant attenuation of EGF-induced PARP cleavage. Our findings support STAT3
      as a positive mediator of EGF-induced apoptosis in MDA-MB-468 cells.

PMID- 28433701
TI  - Thyroid monitoring of adults and children after reactor accidents with a new dose
      rate measurement device.
AB  - A specialized dose rate measurement device that was designed for monitoring the
      thyroid dose of children and adults after reactor accidents was tested. In
      measurements with neck phantoms and a human patient, the device was found to be
      capable of measuring the required low dose rates, even within increased ambient
      radiation. It is suitable for the application in emergency care centers.

PMID- 28433702
TI  - Group B streptococcus and respiratory syncytial virus immunisation during
      pregnancy: a landscape analysis.
AB  - Group B streptococcus and respiratory syncytial virus are leading causes of
      infant morbidity and mortality worldwide. No licensed vaccines are available for
      either disease, but vaccines for both are under development. Severe respiratory
      syncytial virus disease can be prevented by passively administered antibody. The
      presence of maternal IgG antibody specific to respiratory syncytial virus is
      associated with reduced prevalence and severity of respiratory syncytial virus
      disease in the first few weeks of life, whereas maternal serotype-specific
      anticapsular antibody is associated with protection against both early-onset and
      late-onset group B streptococcus disease. Therefore, vaccination in pregnancy
      might protect infants against both diseases. This report describes what is known
      about immune protection against group B streptococcus and respiratory syncytial
      virus, identifies knowledge gaps regarding the immunobiology of both diseases,
      and aims to prioritise research directions in maternal immunisation.

PMID- 28433703
TI  - Corrections.

PMID- 28433704
TI  - Pertussis and influenza immunisation during pregnancy: a landscape review.
AB  - Immunisation during pregnancy is a relatively new strategy, and is currently
      limited to tetanus, pertussis, and influenza vaccines. None of these vaccines
      were developed specifically for use in pregnancy, but they provide an effective
      method of protecting mothers and young infants. In response to increases in
      pertussis morbidity and mortality among young infants, several countries have
      recommended universal tetanus, diphtheria, and acellular pertussis immunisation
      during pregnancy. Similarly, many countries recommend influenza immunisation
      during pregnancy to reduce the risk of disease for mother and infant. Although
      scientific evidence to support maternal immunisation against pertussis and
      influenza is rapidly accumulating, important knowledge gaps remain that need to
      be addressed by future research, which we have highlighted in this Series paper.

PMID- 28433705
TI  - Maternal immunisation: collaborating with mother nature.
AB  - Maternal immunisation has the potential to substantially reduce morbidity and
      mortality from infectious diseases after birth. The success of tetanus,
      influenza, and pertussis immunisation during pregnancy has led to consideration
      of additional maternal immunisation strategies to prevent group B streptococcus
      and respiratory syncytial virus infections, among others. However, many gaps in
      knowledge regarding the immunobiology of maternal immunisation prevent the
      optimal design and application of this successful public health intervention.
      Therefore, we did an innovative landscape analysis to identify research
      priorities. Key topics were delineated through review of the published
      literature, consultation with vaccine developers and regulatory agencies, and a
      collaborative workshop that gathered experts across several maternal immunisation
      initiatives-group B streptococcus, respiratory syncytial virus, pertussis, and
      influenza. Finally, a global online survey prioritised the identified knowledge
      gaps on the basis of expert opinion about their importance and relevance. Here we
      present the results of this worldwide landscape analysis and discuss the
      identified research gaps.

PMID- 28433706
TI  - Global perspectives on maternal immunisation.

PMID- 28433707
TI  - Genetic susceptibility to toxicologic lung responses among inbred mouse strains
      following exposure to carbon nanotubes and profiling of underlying gene networks.
AB  - The risk of human exposure to fiber nanoparticles has risen in recent years due
      to increases in the manufacture and utilization of carbon nanotubes (CNTs). CNTs
      are present as airborne particulates in occupational settings and their hazard
      potential has been demonstrated in experimental lung exposure studies using
      inbred mouse strains. However, it is not known whether different inbred strains
      differ in lung responses to CNTs by virtue of their genetics. In this work,
      common inbred strains (BALB/c, C57Bl/6, DBA/2, and C3H/He) were exposed to CNTs
      via oropharyngeal aspiration and lung histology and bronchoalveolar lavage (BAL)
      samples were evaluated over 28days with the objective of evaluating
      sensitivity/resistance among strains. C57Bl/6 mice developed significantly more
      extensive type II pneumocyte (T2P) hyperplasia and alveolar infiltrate compared
      to DBA/2 mice, which were resistant. Surprisingly, DBA/2 but not C57Bl/6 mice
      were extremely sensitive to increases in leukocytes recovered in BAL fluid.
      Underlying global gene expression patterns in the two strains were compared using
      mRNA sequencing to investigate regulatory networks associated with the different
      effects. The impact of exposure on gene networks regulating various aspects of
      immune response and cell survival was limited in DBA/2 mice compared to C57Bl/6.
      Investigation of B6D2F1 (C57Bl/6*DBA/2 hybrid) mice demonstrated inheritance of
      sensitivity to CNT exposures in regard to toxicologic lung pathology and BAL
      leukocyte accumulations. These findings demonstrate a genetic basis of
      susceptibility to CNT particle exposures and both inform the use of inbred mouse
      models and suggest the likelihood of differences in genetic susceptibility among
      humans.

PMID- 28433708
TI  - Toxicological characterisation of two novel selective aryl hydrocarbon receptor
      modulators in Sprague-Dawley rats.
AB  - The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also
      plays important physiological roles. Selective AHR modulators, which elicit some
      effects imparted by this receptor without causing the marked toxicity of dioxins,
      are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N
      acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3
      carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2
      dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). They represent, as
      diacetyl prodrugs, AHR-active metabolites of the drug compounds laquinimod and
      tasquinimod, respectively, which are intended for the treatment of autoimmune
      diseases and cancer. Here, we toxicologically assessed the novel compounds in
      Sprague-Dawley rats, after a single dose (8.75-92.5mg/kg) and 5-day repeated
      dosing at the highest doses achievable (IMA-08401: 100mg/kg/day; and IMA-07101:
      75mg/kg/day). There were no overt clinical signs of toxicity, but body weight
      gain was marginally retarded, and the treatments induced minimal hepatic
      extramedullary haematopoiesis. Further, both the absolute and relative weights of
      the thymus were significantly decreased. Cyp1a1 gene expression was substantially
      increased in all tissues examined. The hepatic induction profile of other AHR
      battery genes was distinct from that caused by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). The only marked alterations in serum clinical chemistry variables
      were a reduction in triglycerides and an increase in 3-hydroxybutyrate. Liver and
      kidney retinol and retinyl palmitate concentrations were affected largely in the
      same manner as reported for TCDD. In vitro, the novel compounds activated CYP1A1
      effectively in H4IIE cells. Altogether, these novel compounds appear to act as
      potent activators of the AHR, but lack some major characteristic toxicities of
      dioxins. They therefore represent promising new selective AHR modulators.

PMID- 28433709
TI  - Pulmonary pathobiology induced by zinc oxide nanoparticles in mice: A 24-hour and
      28-day follow-up study.
AB  - Inhaled zinc oxide nanoparticles (ZnONPs) have high deposition rates in the
      alveolar region of the lungs; however, the adverse health effects of ZnONPs on
      the respiratory system are unclear. Herein, pathobiological responses of the
      respiratory system of mice that received intratracheal administration of ZnONPs
      were investigated by a combination of molecular and imaging (SPECT and CT)
      approaches. Also, normal BEAS-2B and adenocarcinoma A549 cells were used to
      confirm the results in mice. First, female BALB/c mice were administrated a
      series of doses of 20-nm ZnONPs and were compared to the phosphate-buffered
      saline control for 24-h and 28-day follow-up observations. Field emission
      scanning electron microscopy and an energy-dispersive X-ray microanalysis were
      first used to characterize ZnONPs. After 24h, instilled ZnONPs had caused
      significant increases in lactic dehydrogenase (LDH) in bronchoalveolar lavage
      fluid (BALF) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and the p63
      tumor marker in lung tissues (p<0.05). Airway inflammation was present in a dose
      dependent manner from the upper to the lower airway as analyzed by SPECT. After
      28days, p63 had significantly increased due to ZnONP exposure in lung tissues
      (p<0.05). Pulmonary inflammatory infiltration mainly occurred in the left and
      right subsegments of the secondary bronchial bifurcation as observed by CT. A
      significant increase in p63 and decrease in TTF1 levels were observed in BEAS-2B
      cells by ZnONP (p<0.05), but not in A549 cells. Our results demonstrated that
      regional lung inflammation occurred with ZnONP exposure. We also showed that p63
      was consistently overexpressed due to ZnONP exposure in vivo and in vitro. This
      work provides unique findings on the p63 response and the pathobiology in
      response to ZnONPs, which could be important to the study of pulmonary toxicity
      and repair.

PMID- 28433710
TI  - Down-regulation of islet amyloid polypeptide expression induces death of human
      annulus fibrosus cells via mitochondrial and death receptor pathways.
AB  - Islet amyloid polypeptide (IAPP) exerts its biological effects by participating
      in the regulation of glucose metabolism and cell apoptosis. The main goal of the
      present study was to investigate the expression of IAPP in degenerated
      intervertebral disc tissue and IAPP's modulation of extracellular matrix (ECM)
      catabolic and anabolic genes in human AF cells. We found that the expression of
      IAPP, the calcitonin receptor, and receptor activity modifying protein decreased
      considerably in AF cells during the progression of intervertebral disc
      degeneration (IDD). Meanwhile, transfection with pLV-siIAPP decreased the
      expression of IAPP and its receptors and reduced glucose uptake and the
      expression of aggrecan, Col2A1, and BG. Down-regulation of IAPP also induced a
      significant increase in reactive oxygen species generation in AF cells, along
      with a decrease in matrix metalloproteinases and an increase in the concentration
      of cellular Ca2+, ultimately leading to death. Further analysis revealed that
      siIAPP intervention promoted the release of cytochrome c from mitochondria,
      resulting in the activation of Caspase-3 and Caspase-9. In contrast,
      significantly decreased expression of Caspase-3 and Caspase-9 was observed in AF
      cells transfected with pLV-IAPP. The concentrations of Fas and FasL proteins were
      significantly decreased in AF cells transfected with PLV-IAPP, while activation
      of the Fas/FasL system and cell death were induced by siIAPP intervention.
      Mechanistically, AMPK/Akt-mTOR signaling pathways were involved. In conclusion,
      down-regulation of IAPP expression induces the death of human AF cells via
      mitochondrial and death receptor pathways, potentially offering a novel
      therapeutic target for the treatment of IDD.

PMID- 28433711
TI  - MDH2 is an RNA binding protein involved in downregulation of sodium channel Scn1a
      expression under seizure condition.
AB  - Voltage-gated sodium channel alpha-subunit type I (NaV1.1, encoded by SCN1A gene)
      plays a critical role in the excitability of brain. Downregulation of SCN1A
      expression is associated with epilepsy, a common neurological disorder
      characterized by recurrent seizures. Here we reveal a novel role of malate
      dehydrogenase 2 (MDH2) in the posttranscriptional regulation of SCN1A expression
      under seizure condition. We identified that MDH2 was an RNA binding protein that
      could bind two of the four conserved regions in the 3' UTRs of SCN1A. We further
      showed that knockdown of MDH2 or inactivation of MDH2 activity in HEK-293 cells
      increased the reporter gene expression through the 3' UTR of SCN1A, and MDH2
      overexpression decreased gene expression by affecting mRNA stability. In the
      hippocampus of seizure mice, the upregulation of MDH2 expression contributed to
      the decrease of the NaV1.1 levels at posttranscriptional level. In addition, we
      showed that the H2O2 levels increased in the hippocampus of the seizure mice, and
      H2O2 could promote the binding of MDH2 to the binding sites of Scn1a gene,
      whereas beta-mercaptoethanol decreased the binding capability, indicating an
      important effect of the seizure-induced oxidation on the MDH2-mediated
      downregulation of Scn1a expression. Taken together, these data suggest that MDH2,
      functioning as an RNA-binding protein, is involved in the posttranscriptional
      downregulation of SCN1A expression under seizure condition.

PMID- 28433712
TI  - Common PHOX2B poly-alanine contractions impair RET gene transcription,
      predisposing to Hirschsprung disease.
AB  - HSCR is a congenital disorder of the enteric nervous system, characterized by the
      absence of neurons along a variable length of the gut resulting from loss-of
      function RET mutations. Congenital Central Hypoventilation Syndrome (CCHS) is a
      rare neurocristopathy characterized by impaired response to hypercapnia and
      hypoxemia caused by heterozygous mutations of the PHOX2B gene, mostly polyalanine
      (polyA) expansions but also missense, nonsense, and frameshift mutations, while
      polyA contractions are common in the population and believed neutral. HSCR
      associated CCHS can present in patients carrying PHOX2B mutations. Indeed, RET
      expression is orchestrated by different transcriptional factors among which
      PHOX2B, thus suggesting its possible role in HSCR pathogenesis. Following the
      observation of HSCR patients carrying in frame trinucleotide deletions within the
      polyalanine stretch in exon 3 (polyA contractions), we have verified the
      hypothesis that these PHOX2B variants do reduce its transcriptional activity,
      likely resulting in a down-regulation of RET expression and, consequently,
      favouring the development of the HSCR phenotype. Using proper reporter
      constructs, we show here that the in vitro transactivation of the RET promoter by
      different HSCR-associated PHOX2B polyA variants has resulted significantly lower
      compared to the effect of PHOX2B wild type protein. In particular, polyA
      contractions do induce a reduced transactivation of the RET promoter, milder
      compared to the severe polyA expansions associated with CCHS+HSCR, and correlated
      with the length of the deleted trait, with a more pronounced effect when
      contractions are larger.

PMID- 28433714
TI  - Effects of dietary supplementation with fenugreek seeds, alone or in combination
      with probiotics, on gilthead seabream (Sparus aurata L.) skin mucosal immunity.
AB  - Despite increasing interest in modulating the immune response of fish, providing
      a combination of probiotics and herbal immunostimulants in aquafeed has rarely
      has been studied. The effects on gilthead seabream (Sparus aurata L.) of the
      dietary administration of fenugreek (Trigonella foenum graecum) seeds alone (FE),
      or combined with one of the following probiotic strains: Bacillus licheniformis
      (FEBL), Lactobacillus plantarum (FELP) or Bacillus subtilis (FEBS) were
      evaluated. Fish were fed a control or one of the supplemented diets for 3 weeks.
      After 2 and 3 weeks of the feeding trial, the abundance of terminal
      carbohydrates, IgM levels, enzymatic activities (proteases, alkaline phosphatase,
      esterase and ceruloplasmin) and bactericidal activity were determined in skin
      mucus. Our results demonstrated that the dietary administration of FE in
      combination with L. plantarum, particularly, increased carbohydrate abundance,
      the activity of certain enzymes such as ceruloplasmin, and bactericidal activity
      against the pathogenic bacterium Photobacterium damselae and the non-pathogenic
      bacterium B. subtilis in skin mucus at the end of the trial. The carbohydrates
      most affected by the FELP diet were mannose/glucose, N-acetyl-d-galactosamine and
      N-acetyl-beta-d-glucosamine. Interestingly, IgM levels were significantly higher
      in fish fed the FELP and FEBS diets whilst protease activity generally increased
      in all supplemented diets, which could suggests that the main effect in this
      activity was to the result of FE supplementation although that fact cannot be
      confirmed because the effects of probiotics addition alone were not studied.
      These results suggest that the combined dietary administration of fenugreek and
      L. plantarum will best enhance the skin mucosal immunity response of gilthead
      seabream.

PMID- 28433715
TI  - Aloe vera enhances the innate immune response of pacu (Piaractus mesopotamicus)
      after transport stress and combined heat killed Aeromonas hydrophila infection.
AB  - In this study, pacu (Piaractus mesopotamicus) were fed with diets containing Aloe
      vera for 10 days prior to transport stress and infection with heat killed
      Aeromonas hydrophila. A. vera is popular around the world due to its medicinal
      properties, including immunostimulatory effects which was observed in this study.
      The results show that transport causes immunosuppression, an effect that was
      prevented by A. vera. Specifically, A. vera prevented reductions of both
      leukocyte respiratory burst and hemolytic activity of complement system caused by
      transport. Further, fish fed with A. vera also showed significantly higher
      leukocyte respiratory burst, serum lysozyme concentrations and activity of
      complement system 24 h after bacterial infection. Additionally, we observed that
      A. vera may modulate the innate response through activation of complement system
      during bacterial immune stimulation. In summary, A. vera extract enhanced innate
      immune parameters and consequently the ability of fish to cope with pathogens
      following transport stress. These findings show that A. vera has promise for use
      in aquaculture and add further evidence that medicinal herbs added to fish feed
      assist to prevent disease outbreaks.

PMID- 28433713
TI  - Biased signaling at neural melanocortin receptors in regulation of energy
      homeostasis.
AB  - The global prevalence of obesity highlights the importance of understanding on
      regulation of energy homeostasis. The central melanocortin system is an important
      intersection connecting the neural pathways controlling satiety and energy
      expenditure to regulate energy homeostasis by sensing and integrating the signals
      of external stimuli. In this system, neural melanocortin receptors (MCRs),
      melanocortin-3 and -4 receptors (MC3R and MC4R), play crucial roles in the
      regulation of energy homeostasis. Recently, multiple intracellular signaling
      pathways and biased signaling at neural MCRs have been discovered, providing new
      insights into neural MCR signaling. This review attempts to summarize biased
      signaling including biased receptor mutants (both naturally occurring and lab
      generated) and biased ligands at neural MCRs, and to provide a better
      understanding of obesity pathogenesis and new therapeutic implications for
      obesity treatment.

PMID- 28433716
TI  - Development of a monoclonal antibody against the CD3epsilon of olive flounder
      (Paralichthys olivaceus) and its application in evaluating immune response
      related to CD3epsilon.
AB  - The T cell receptor (TCR) is the binding site of antigen and is responsible for
      specifically activating the adaptive immune response. CD3, an essential component
      of the CD3-TCR complex, is known to be composed of gammadelta and epsilon chains
      in teleost. However, there are few monoclonal antibodies (mAb) available to
      identify these molecules on T cells, so we aimed to produce a mAb against
      CD3epsilon to improve our understanding of T cell immune response in olive
      flounder (Paralichthys olivaceus). CD3epsilon recombinant protein was expressed
      in yeast, the expression of which was confirmed by SDS-PAGE, MALDI-TOF/TOF MS and
      Western blot analysis. A CD3epsilon-specific mAb 4B2 was selected, the
      specificity of which was examined by confocal microscopy, flow cytometry and RT
      PCR, and the mAb was subsequently used to examine the CD3epsilon lymphocyte
      population in several different immune organs, with relatively high percentages
      of these cells seen in trunk-kidney and spleen, while lower percentages were seen
      in the liver and peripheral blood of olive flounder. During a viral hemorrhagic
      septicemia virus (VHSV) infection in olive flounder, the number of CD3epsilon
      lymphocytes was seen to gradually increase in the liver, spleen and trunk-kidney
      of infected fish until 7 days post infection (dpi). In peripheral blood, on the
      other hand, the increase in CD3epsilon lymphocyte numbers peaked by 3 dpi. These
      results suggest that CD3epsilon lymphocytes might be involved in the immune
      response against VHSV.

PMID- 28433717
TI  - Response a chronic effects of PBDE-47: Up-regulations of HSP60 and HSP70
      expression in freshwater bivalve Anodonta woodiana.
AB  - Heat shock proteins (HSPs) play an important role in adaption of environmental
      stress by protein folding, membrane translocation, degradation of misfolded
      proteins and other regulatory processes. Our previous study showed oxidative
      stress generated from polybrominated diphenyl ether-47 (PBDE-47) could cause an
      acute toxicity on freshwater bivalve Anodonta Woodiana, but the effect of chronic
      toxicity need to be elucidated. In order to further investigate the chronic
      effect of PBDE-47, clams A. Woodiana were randomly divided into the PBDE-47
      treated group administrated with PBDE-47 at a concentration 3.36 MUg/L and
      control group treated with a similar volume dimethyl sulfoxide. Two complete HSP
      sequences were isolated from A. Woodianaa and respectively named AwHSP60 and
      AwHSP70. They were widely distributed in foot, gill, hepatopancreas, adductor
      muscle, heart, hemocytes and mantle. Administration of PBDE-47 could result in a
      significant up-regulation of AwHSP60 and AwHSP70 expressions in the
      hepatopancreas, gill and hemocytes. In the hepatopancreas, compared with that of
      control group, mRNA level of AwHSP60 increased more than 89.9% (P < 0.05) from
      day 1-15, AwHSP70 increased more 2.79 times (P < 0.01). In the gill, during
      experiment observed, expression of AwHSP60 increased more 2.09 times (P < 0.01)
      in contrasted with that of control group. Significant up-regulation of AwHSP70
      expression showed a reversed U shape. In the hemocytes, AwHSP60 and AwHSP70
      expressions of PBDE-47 treated group respectively increased more 2.09 times (P <
      0.05) and 1.81 times (P < 0.05) compared with that of control group. These
      results indicated that up-regulations of AwHSP60 and AwHSP70 expression are
      contribute to enhancing adaption of bivalve A. Woodiana exposed to PBDE-47
      treatment.

PMID- 28433718
TI  - Three new piscidins from orange-spotted grouper (Epinephelus coioides):
      Phylogeny, expression and functional characterization.
AB  - The present study reports the identification, and characterization of three new
      putative piscidin paralogues, ecPis-2, ecPis-3 and ecPis-4, from orange-spotted
      grouper (Epinephelus coioides). The cDNA of the three piscidins with the 207,
      216, and 231 nt open reading frame encoded respectively a 68-, 71-, and 76-amino
      acid preprotein consisting of the predicted signal peptide, and putative mature
      peptide and prodomain. The phylogenetic analysis indicated that multiple piscidin
      paralogues in one fish species are highly diversified, the analysis suggested
      that the piscidins should be a family belonging to the superfamily of ancient
      cationic, linear, and amphipathic host defence peptides widespread across
      invertebrate and vertebrate taxa comprising insect cecropins and ceratotoxins,
      and the amphibian dermaseptins. The synthetic putative mature peptides, ecPis-2S,
      ecPis-3S and ecPis-4S, had strong activities against bacterial and fungal
      species. EcPis-3S exhibited powerful activity against the infective stage of
      Cryptocaryon irritans, theronts. The full length ecPis-2 and ecPis-4 by removal
      of signal peptide, ecPis-2L and ecPis-4L respectively, had potency against
      bacterial, fungal and parasitic species. The peptide ecPis-2S was proved to exist
      in spleen of orange-spotted grouper by HPLC followed by ESI-LCMS analysis. Basal
      transcriptions of ecPis-2, ecPis-3 and ecPis-4 were detected not only in the
      potential sites of pathogen entry such as gills, skin and intestine, but also in
      tissues such as head kidney, trunk kidney, blood cells, and spleen with highly
      abundant immune cells, however different paralogues expressed constitutively with
      different levels in the tissues. In addition, the expression of ecPis-2, ecPis-3
      and ecPis-4 was upregulated in orange-spotted grouper challenged by Vibrio
      Parahaemolyticus, in different tissues at different time point after bacteria
      injection. These results support ecPis-2, ecPis-3 and ecPis-4 being the important
      immune-related genes in orange-spotted grouper innate immune system and playing
      multifunctional and complementary roles following their structural and functional
      diversification, and expression pattern difference. Finally, this study
      facilitates the evaluation of ecPis-2S, 2L, ecPis-3S, and ecPis-4S, -4L as
      potential templates of therapeutic agents against pathogens.

PMID- 28433719
TI  - Isolation and characterization of monocyte/macrophage from peripheral blood of
      half smooth tongue sole (Cynoglossus semilaevis).
AB  - In the present study, the peripheral blood cells of half smooth tongue sole
      (Cynoglossus semilaevis) were examined by blood smear under the light microscopy.
      The proportion of main types of blood cells are as following: erythrocyte
      occupied the majority (92.3%), followed by thrombocyte (4.15%), granulocyte
      (1.7%), lymphocyte (1.5%) and monocyte (0.3%), respectively. Meanwhile, the
      isolation method of monocytes was established, by density gradient centrifugation
      to isolate mononuclear leukocytes of peripheral blood. In primary culture, the
      monocytes were adhered to the bottom of the flask without feeder cells and
      separated easily with suspended leukocytes in the medium in 3 h. After suspended
      leukocytes were removed, the monocytes multiplied rapidly with the two doubly
      during the 24 h, then the cells proliferated and kept stable until 48 h. When co
      cultured with suspended leukocytes after three days, the monocytes could derive
      to typical macrophages, of which the size enlarged significantly and showed
      various forms such as like fried eggs, and giant irregular shape with pseudopod
      because cells fusion or deformation occurred until macrophages died in about two
      weeks. Monocytes showed strong respiratory burst activity after treated with
      Phorbol ester PMA and challenged by bacteria respectively. In addition,
      macrophage of half smooth tongue sole had typical macrophage features such as
      phagocytic capability, positive esterase activity, and the considerable
      expression of M-CSFR, MHC-II, IL-6, IL-10, TNF and arginase genes. That arginase
      expression in macrophages (3d and 5d after differentiation) was upregulated
      fluctuant suggest that the cultivation was mixture of alternatively activated
      type macrophage (M2) in the majority while the classically activated type (M1)
      win the minority. Furthermore, MHC-II, M-CSFR and IL-6 were significantly induced
      following LPS challenge. Collectively, the present study will be useful for the
      study on half smooth tongue sole immune systems and immune function.

PMID- 28433720
TI  - Establishment of a non-invasive method for stress evaluation in farmed salmon
      based on direct fecal corticoid metabolites measurement.
AB  - Fish welfare is an important issue for growth of the aquaculture industry. Stress
      responses represent animal's natural reactions to challenging conditions and
      could be used as a welfare indicator. Cortisol level is relevant to fish welfare
      condition, and is a readily measured component of the primary stress response
      system. Generally, cortisol is measured by blood sampling. However, fish blood
      cortisol level could be instantly influenced by handling-stress at sampling.
      Fecal corticoid metabolites (FCM) are a mixture of several different metabolites
      with a wide range of polarities. Thus, feces could be promising alternative less
      handling-sensitive and non-invasive biological matrices for cortisol evaluation
      in Atlantic salmon. In this study we developed non-invasive method for
      determination of fecal corticoid metabolites in farmed Atlantic salmon (Salmo
      salar L.) using enzyme-linked immunosorbent assay (ELISA). It was demonstrated
      that salmon FCM extracted from salmon feces is insoluble in non-polar solvents
      like diethyl ether, but well soluble in polar solvents like methanol. The proper
      extraction ratio could be one ml 100% methanol for 100 MUL of the liquid part of
      salmon feces or 100 mg of the solid part. The FCM directly detected in
      unextracted liquid part of feces correlated well with the FCM extracted from both
      liquid and solid part of the corresponding samples, without significant
      difference. Thus, it is feasible to measure FCM directly in the liquid part of
      salmon feces without any extraction procedure. Then, we applied this assay for
      FCM analysis in the group of salmon that experienced salmon pancreas disease (PD)
      and amoebic gill disease (AGD). We demonstrated 1) both plasma cortisol and FCM
      increased significantly during the outbreak of inflammatory disease (P < 0.01).
      Plasma cortisol level was elevated from 28 +/- 40 ng/ml to 164.4 +/- 62.5 ng/ml,
      FCM from 14.4 +/- 13.2 ng/ml to 170.7 +/- 89.7 ng/ml 2) Growth and starvation has
      no significant impact on either cortisol or FCM level. 3) FCM correlated well
      with plasma cortisol level (P < 0.01). Furthermore, there seems more individual
      variation in plasma cortisol levels than in FCM levels. These results suggest FCM
      could be directly analyzed in liquid part of salmon feces without extraction.
      This directly detected FCM level could represent the total fecal FCM level and
      plasma cortisol level. This simple and non-invasive method makes FCM a proper
      indicator for salmon welfare.

PMID- 28433721
TI  - Optimizing the restored chemotactic behavior of anticancer agent Salmonella
      enterica serovar Typhimurium VNP20009.
AB  - Bacteria, including strains of Salmonella, have been researched and applied as
      therapeutic cancer agents for centuries. Salmonella are particularly of interest
      due to their facultative anaerobic nature, facilitating colonization of
      differentially oxygenated tumor regions. Additionally, Salmonella can be
      manipulated with relative ease, resulting in the ability to attenuate the
      pathogen or engineer vectors for drug delivery. It was recently discovered that
      the anti-cancer Salmonella enterica serovar Typhimurium strain VNP20009 is
      lacking in chemotactic ability, due to a non-synonymous single nucleotide
      polymorphism in cheY. Replacing the mutated copy of cheY with the wild-type
      sequence restored chemotaxis to 70% of the parental strain. We aimed to
      investigate further if chemotaxis of VNP20009 can be optimized. By restoring the
      gene msbB in VNP20009 cheY+, which confers attenuation by lipid A modification,
      we observed a 9% increase in swimming speed, 13% increase in swim plate
      performance, 19% increase in microfluidic device partitioning towards the
      attractant at the optimum concentration gradient, and mitigation of a non-motile
      cell subpopulation. We conclude that chemotaxis can be enhanced further but at
      the cost of changing one defining characteristic of VNP20009. A less compromised
      strain might be needed to employ for investigating bacterial chemotaxis in tumor
      interactions.

PMID- 28433722
TI  - High precision genome sequencing of engineered Gluconobacter oxydans 621H by
      combining long nanopore and short accurate Illumina reads.
AB  - State of the art and novel high-throughput DNA sequencing technologies enable
      fascinating opportunities and applications in the life sciences including
      microbial genomics. Short high-quality read data already enable not only
      microbial genome sequencing, yet can be inadequately to solve problems in genome
      assemblies and for the analysis of structural variants, especially in engineered
      microbial cell factories. Single-molecule real-time sequencing technologies
      generating long reads promise to solve such assembly problems. In our study, we
      wanted to increase the average read length of long nanopore reads with R9
      chemistry and conducted a hybrid approach for the analysis of structural variants
      to check the genome stability of a recombinant Gluconobacter oxydans 621H strain
      (IK003.1) engineered for improved growth. Therefore we combined accurate Illumina
      sequencing technology and low-cost single-molecule nanopore sequencing using the
      MinION(r) device from Oxford Nanopore. In our hybrid approach with a modified
      library protocol we could increase the average size of nanopore 2D reads to about
      18.9kb. Combining the long MinION nanopore reads with the high quality short
      Illumina reads enabled the assembly of the engineered chromosome into a single
      contig and comprehensive detection and clarification of 7 structural variants
      including all three known genetically engineered modifications. We found the
      genome of IK003.1 was stable over 70 generations of strain handling including 28h
      of process time in a bioreactor. The long read data revealed a novel 1420 bp
      transposon-flanked and ORF-containing sequence which was hitherto unknown in the
      G. oxydans 621H reference. Further analysis and genome sequencing showed that
      this region is already present in G. oxydans 621H wild-type strains. Our data of
      G. oxydans 621H wild-type DNA from different resources also revealed in 73
      annotated coding sequences about 91 uniform nucleotide differences including
      InDels. Together, our results contribute to an improved high quality genome
      reference for G. oxydans 621H which is available via ENA accession PRJEB18739.

PMID- 28433723
TI  - Elimination of the cryptic plasmid in Leuconostoc citreum by CRISPR/Cas9 system.
AB  - Leuconostoc spp. are important lactic acid bacteria for the fermentation of
      foods. In particular, L. citreum strains isolated from various foods have been
      used as host strains for genetic and metabolic engineering studies. In order to
      develop a food-grade genetic engineering system, L. citreum CB2567 was isolated
      from Kimchi. However, the isolated bacterium contained a cryptic plasmid which
      was difficult to eliminate. As the existence of the plasmid might hinder strain
      engineering, we eliminated the plasmid using an RNA-guided DNA endonuclease
      CRISPR/Cas9 system. We demonstrated that a plasmid-free L. citreum CB2567 host
      strain could be efficiently constructed through a two-step procedure: 1)
      transformation of the "killer" plasmid expressing Cas9 endonuclease and a guide
      RNA (gRNA) targeting for a specific sequence in the cryptic plasmid, and 2)
      serial subculture without antibiotics for curing the killer plasmid. When the
      crude extract of L. citreum expressing Cas9 and the guide RNA was incubated with
      a PCR fragment containing the specific sequence recognized by the guide RNA, the
      PCR fragment was cleaved. Also, the cryptic plasmid pCB42 was successfully
      eliminated from the host strain after transforming the plasmid harboring Cas9 and
      the guide RNA. The Cas9 and gRNA expression plasmid used in this study can be
      applied for genome engineering purposes by additionally introducing an editing
      DNA template to repair the double strand DNA breakage caused by Cas9 in the
      genome of L. citreum. This study demonstrates the feasibility of developing
      CRISPR/Cas9-based genetic engineering tools to develop a safe host strain and
      construct food-grade lactic acid bacteria without residual antibiotic markers.

PMID- 28433724
TI  - Whole-genome de novo sequencing of wood rot fungus Fomitopsis palustris
      (ATCC62978) with both a cellulolytic and ligninolytic enzyme system.
AB  - Fomitopsis palustris is a model brown rot fungus causing destructive wood decay
      based on the cellulase system. Endoglucanase secreted by F. palustris hydrolyzes
      cellulose in both the crystalline and amorphous form. In this study, whole-genome
      sequencing was conducted to identify genes related to F. palustris cellulose
      degradation and their functions. We determined the 43-Mb complete draft genome of
      F. palustris (ATCC 62978), comprising 14,592 predicted gene models. Gene
      annotation provided crucial information about the location and function of
      protein-encoding genes. Three types of endoglucanases were expressed: endo-1,3
      beta-glucanase, endo-1,4-beta-d-glucanase, and endoglucanase. In addition,
      various ligninolytic enzymes such as laccase, aromatic compound dioxygenase, and
      aryl alcohol dehydrogenase were expressed in F. palustris (ATCC 62978). Colony
      polymerase chain reaction (PCR) indicated that the endo-1,4-beta-d-glucanase gene
      comprises 732bp. Optimization of the expression conditions of endoglucanase by
      real-time PCR revealed that endoglucanase was highly expressed after 7days in all
      conditions, which was secreted during the secondary metabolism. Studies for large
      scale cellulase production from this fungus and investigation of its ligninolytic
      system will promote its extensive use in various applications. The genomic
      information determined herein provides a basis for molecular genetics studies to
      understand the genome functions of F. palustris (ATCC 62978).

PMID- 28433726
TI  - Managing responsible antimicrobial use: perspectives across the healthcare
      system.
AB  - BACKGROUND: Healthcare systems consist of building blocks. Shaping how these
      building blocks function and interact can promote responsible antimicrobial use,
      and this represents an important opportunity for managers at different points
      within healthcare systems to act upon. AIMS: To review real-world examples of how
      healthcare systems can promote responsible antimicrobial use, focusing on the
      role of governance and managers. SOURCES: We searched and reviewed existing
      literature and official documents, which mostly focused on antibiotics. We also
      drew on the diverse experiences of the ESGAP (the ESCMID (European Society of
      Clinical Microbiology and Infectious Diseases) Study Group for Antimicrobial
      stewardshiP) network. CONTENT: First, we explored at the institution level the
      implementation of antimicrobial stewardship programmes, the need to embrace
      multidisciplinary approaches, the benefits of engaging with social sciences
      experts, and the role of governance and leadership. We look beyond individual
      institutions and highlight the urgent need for workforce capacity estimates for
      antimicrobial stewardship activities, how antimicrobial stewardship efforts can
      connect to form networks, and the importance of governance and regulation at
      national and international levels. IMPLICATIONS: Managers in the healthcare
      system are in a strong position to look beyond individual prescriptions and to
      recognize the many ways in which different healthcare system building blocks can
      contribute to responsible use of antimicrobials. At the institution level this
      can be achieved by implementing antimicrobial stewardship programmes, ensuring
      they are adequately resourced, and driving buy-in across clinical leadership. At
      regional and national levels this includes facilitating the sharing of
      experiences and resources between institutions, and developing the standards and
      regulations needed to support responsible antimicrobial use.

PMID- 28433725
TI  - Clinical characteristics and surgical treatment of spinal paraganglioma: A case
      series of 18 patients.
AB  - BACKGROUND AND OBJECTIVES: Paraganglioma rarely develops in the spine. With few
      cases reported, little knowledge about this disease was known. The objective of
      this study is to illustrate the clinical features, imaging manifestations,
      pathological appearances and long-term outcomes of the consecutive surgeries by
      literature review. METHODS: The clinical and follow-up data of 18 patients who
      were diagnosed of spinal paraganglioma and treated with surgeries in our
      hospitals from 2003 to 2014 were retrospectively analyzed. RESULT: A total of
      fourteen patients radiographed of intra-spinal tumor underwent extra-capsular
      tumor resection. Of five patients with obvious vertebral bone damage, four cases
      underwent piecemeal resection, and the left one with sacral tumor underwent en
      bloc tumor excision. Spinal reconstruction was performed in all cases. Follow-up
      lasted for 16-96 months (44.1 months on average). There was no local recurrence
      or distant metastasis in cases without obvious bone invasion. Of those five cases
      with vertebral bone damage, one case suffered and survived from the repeat
      relapse of T1 vertebral body tumor. Local recurrence was not observed in one case
      with T10 vertebral tumor after tumor resection, but the tumor metastasized to T2
      attachment during the follow-up and was finally eradicated by re-operation. No
      tumor recurrence was observed in the left three cases. CONCLUSION: Paraganglioma,
      usually benign, rarely occurs. Surgical resection, especially complete surgical
      resection, is preferred to treat spinal paraganglioma. Chemotherapy,
      radiotherapy, use of octreotide and other somatostatin are selected as adjuvant
      therapies, but their effects remain unknown.

PMID- 28433727
TI  - Superficial swab versus deep-tissue biopsy for the microbiological diagnosis of
      local infection in advanced-stage pressure ulcers of spinal-cord-injured
      patients: a prospective study.
AB  - OBJECTIVE: To assess the predictive value of superficial ulcer swab culture to
      make a microbiological diagnosis of deep wound infections in spinal cord injury
      (SCI) patients with advanced-stage pressure ulcers. METHODS: From July 2011 to
      February 2014, we performed a prospective, single-centre study on adult SCI
      patients undergoing scheduled surgical debridement and reconstruction for
      advanced-stage pressure ulcers, at Montecatone Rehabilitation Institute, a 150
      bed hospital dedicated to SCI care. Three superficial ulcer swabs were
      preoperatively collected using the Levine technique, then sent for culture. In
      surgery, multiple bone and soft-tissue specimens were taken and sent for culture
      and histological examination. No antibiotics were administered before surgery.
      The results of swabs and intraoperative specimens were compared. RESULTS: In all,
      116 patients were included, median age 49 years; a majority were males with post
      traumatic paraplegia. According to intraoperative specimen cultures, the most
      common micro-organisms were Staphylococcus aureus, Proteus mirabilis, and
      Pseudomonas aeruginosa, found in 31, 27, and 16 cases, respectively. Concordance
      between superficial swabs and intraoperative specimen culture was found in only
      in 25 out of 116 cases (22%). The main reason for non-concordance was the
      yielding of different micro-organisms (41 out of 116); false negatives (swab
      negative/intraoperative positive) accounted for 31 out of 116 and false positives
      (swab positive/intraoperative negative) for 19 out of 116. When compared with
      intraoperative specimens, sensitivity and specificity of the swab culture were
      80% and 54%, respectively. CONCLUSIONS: Our results confirm that in patients with
      advanced-stage pressure ulcers, the cultures of a superficial ulcer swab are not
      useful in either the diagnosis of a superinfection or the prediction of the role
      of involved micro-organisms.

PMID- 28433728
TI  - Vector competence of Amblyomma americanum (Acari: Ixodidae) for Rickettsia
      rickettsii.
AB  - Rickettsia rickettsii - the etiologic agent of Rocky Mountain spotted fever
      (RMSF) - is widely spread across the Americas. In the US, Dermacentor spp. ticks
      are identified as primary vectors of R. rickettsii and Rhipicephalus sanguineus
      s.l. has been implicated in transmission of this pathogen in several locations in
      the Southwest. Conversely, ticks of the genus Amblyomma are recognized vectors of
      RMSF in Central and South America, but not in the US. A. americanum is one of the
      most aggressive human-biting ticks in the US, whose geographical range overlaps
      with that of reported RMSF cases. Despite sporadic findings of R. rickettsii DNA
      in field-collected A. americanum and circumstantial association of this species
      with human RMSF cases, its vector competence for R. rickettsii has not been
      appropriately studied. Therefore, we assessed the ability of A. americanum to
      acquire and transmit two geographically distant isolates of R. rickettsii. The Di
      6 isolate of R. rickettsii used in this study originated in Virginia and the AZ-3
      isolate originated in Arizona. Under laboratory conditions, A. americanum
      demonstrated vector competence for both isolates, although the efficiency of
      acquisition and transovarial transmission was higher for Di-6 than for AZ-3
      isolate. Uninfected larvae acquired the pathogen from systemically infected
      guinea pigs, as well as while feeding side by side with Rickettsia-infected ticks
      on non-rickettsiemic hosts. Once acquired, R. rickettsii was successfully
      maintained through the tick molting process and transmitted to susceptible
      animals during subsequent feedings. Guinea pigs and dogs infested with infected
      A. americanum developed fever, scrotal edema and dermatitis or macular rash. R.
      rickettsii DNA was identified in animal blood, skin, and internal organs. The
      prevalence of infection within tick cohorts gradually increased due to side-by
      side feeding of infected and uninfected individuals from 33 to 49% in freshly
      molted nymphs to 71-98% in engorged females. Moreover, R. rickettsii was
      transmitted transovarially by approximately 28% and 14% of females infected with
      Di-6 and AZ-3 isolates, respectively. Hence, A. americanum is capable of
      acquiring, maintaining and transmitting R. rickettsii isolates originating from
      two different geographical regions of the US, at least under laboratory
      conditions. Its role in ecology and epidemiology of RMSF in the US deserves
      further investigation.

PMID- 28433730
TI  - Detection of Rickettsia helvetica and Candidatus R. tarasevichiae DNA in Ixodes
      persulcatus ticks collected in Northeastern European Russia (Komi Republic).
AB  - The number of tick-borne infections in the northern European regions of Russia
      has increased considerably in the last years. In the present study, 676 unfed
      adult Ixodes persulcatus ticks were collected in the Komi Republic from 2011 to
      2013 to study tick-borne rickettsioses. Rickettsia spp. DNA was detected by PCR
      in 51 (7.6%) ticks. The nucleotide sequence analysis of gltA fragments (765bp)
      from 51 ticks indicated that 60.8% and 39.2% of the ticks were infected with
      Rickettsia helvetica and Candidatus R. tarasevichiae, respectively. The gltA
      fragments showed 100% identity with those of Candidatus R. tarasevichiae
      previously discovered in Siberia and China, whereas R. helvetica showed 99.9%
      sequence identity with European isolates. The ompB had 8 nucleotide
      substitutions, 6 of which resulted in amino acid substitutions. In the sca9 gene,
      3 nucleotide substitutions were detected, and only one resulted in amino acid
      substitution. The smpA, ompW, and beta-lactamase genes of R. helvetica also
      showed a high level of sequence identity.

PMID- 28433731
TI  - Effectiveness of a role-play simulation program involving the sbar technique: A
      quasi-experimental study.
AB  - BACKGROUND: Accurate, skilled communication in handover is of high priority in
      maintaining patients' safety. Nursing students have few chances to practice nurse
      to-doctor handover in clinical training, and some have little knowledge of what
      constitutes effective handover or lack confidence in conveying information.
      OBJECTIVES: This study aimed to develop a role-play simulation program involving
      the Situation, Background, Assessment, Recommendation technique for nurse-to
      doctor handover; implement the program; and analyze its effects on situation,
      background, assessment, recommendation communication, communication clarity,
      handover confidence, and education satisfaction in nursing students. DESIGN: Non
      equivalent control-group pretest-posttest quasi-experimental. PARTICIPANTS: A
      convenience sample of 62 senior nursing students from two Korean universities.
      METHOD: The differences in SBAR communication, communication clarity, handover
      confidence, and education satisfaction between the control and intervention
      groups were measured before and after program participation. RESULTS: The
      intervention group showed higher Situation, Background, Assessment,
      Recommendation communication scores (t=-3.05, p=0.003); communication clarity
      scores in doctor notification scenarios (t=-5.50, p<0.001); and Situation,
      Background, Assessment, Recommendation education satisfaction scores (t=-4.94,
      p<0.001) relative to those of the control group. There was no significant
      difference in handover confidence between groups (t=-1.97, p=0.054). CONCLUSIONS:
      The role-play simulation program developed in this study could be used to promote
      communication skills in nurse-to-doctor handover and cultivate communicative
      competence in nursing students.

PMID- 28433729
TI  - Comparative vertical transmission of Rickettsia by Dermacentor variabilis and
      Amblyomma maculatum.
AB  - The geographical overlap of multiple Rickettsia and tick species coincides with
      the molecular detection of a variety of rickettsial agents in what may be novel
      tick hosts. However, little is known concerning transmissibility of rickettsial
      species by various tick hosts. To examine the vertical transmission potential
      between select tick and rickettsial species, two sympatric species of ticks,
      Dermacentor variabilis and Amblyomma maculatum, were exposed to five different
      rickettsial species, including Rickettsia rickettsii, Rickettsia parkeri,
      Rickettsia montanensis, Rickettsia amblyommatis, or flea-borne Rickettsia felis.
      Fitness-related metrics including engorgement weight, egg production index,
      nutrient index, and egg hatch percentage were then assessed. Subsamples of egg
      clutches and unfed larvae, nymphs, and adults for each cohort were assessed for
      transovarial and transstadial transmission of rickettsiae by qPCR. Rickettsial
      exposure had a minimal fitness effect in D. variabilis and transovarial
      transmission was observed for all groups except R. rickettsii. In contrast,
      rickettsial exposure negatively influenced A. maculatum fitness and transovarial
      transmission of rickettsiae was demonstrated only for R. amblyommatis- and R.
      parkeri-exposed ticks. Sustained maintenance of rickettsiae via transstadial
      transmission was diminished from F1 larvae to F1 adults in both tick species. The
      findings of this study suggest transovarial transmission specificity may not be
      tick species dependent, and sustained vertical transmission is not common.

PMID- 28433732
TI  - The clinical significance of an estimated fetal weight below the 10th percentile:
      a comparison of outcomes of <5th vs 5th-9th percentile.
AB  - BACKGROUND: The association between small-for-gestational-age (birthweight <10th
      percentile for gestational age) and neonatal morbidity is well established. Yet,
      there is a paucity of data on the relationship between suspected small for
      gestational age (sonographic-estimated fetal weight <10th percentile) at 2
      thresholds and subsequent neonatal morbidity. OBJECTIVE: The objective of this
      study was to determine the relationship between sonographic-estimated fetal
      weight <5th percentile vs 5-9th percentile and neonatal morbidity. STUDY DESIGN:
      This retrospective study involved 5 centers and included nonanomalous, singletons
      with sonographic-estimated fetal weight <10th percentile for gestational age who
      delivered from 2009-2012. Composite neonatal morbidity included respiratory
      distress syndrome, proven sepsis, intraventricular hemorrhage grade III or IV,
      necrotizing enterocolitis, thrombocytopenia, seizures, or death. Odd ratios were
      adjusted for center, maternal age, race, body mass index at first visit, smoking
      status, use of alcohol, use of drugs, and neonatal gender. RESULTS: Of 834 women
      with suspected small-for-gestational-age fetuses, 513 (62%) had sonographic
      estimated fetal weight <5th percentile, and 321 (38%) had sonographic-estimated
      fetal weight of 5-9th percentile for gestational age. At delivery, 81% of women
      with a suspected small-for-gestational-age fetus had a confirmed small-for
      gestational-age fetus. In the group with a sonographic-estimated fetal weight
      <5th percentile, 59% of neonates had birthweight <5th percentile; in the group
      with a sonographic-estimated fetal weight 5-9th percentile, 41% had birthweight
      <5th percentile, and 36% had birthweight at 5-9th percentile. Neonatal intensive
      care unit admission differed significantly for those fetuses at <5th percentile
      (29%) compared with those fetuses at 5-9th percentile (15%; P<.001). The
      composite neonatal morbidity among the sonographic-estimated fetal weight <5th
      percentile group was higher than the sonographic-estimated fetal weight of 5-9th
      percentile group (31% vs 13%; adjusted odds ratio, 2.41; 95% confidence interval,
      1.53-3.80). Similar findings were noted when the analysis was limited to
      sonographic-estimated fetal weight within 28 days of delivery (adjusted odds
      ratio, 2.22; 95% confidence interval, 1.34-3.67). CONCLUSION: Eight of 10
      suspected small-for-gestational-age fetuses had birthweight <10th percentile for
      gestational age; the prediction of actual birthweight was more accurate in the
      <5th percentile group. Neonates with sonographic-estimated fetal weight of <5th
      percentile were more likely to be admitted to the neonatal intensive care unit
      and have complications than were those neonates with sonographic-estimated fetal
      weight of 5-9th percentile.

PMID- 28433733
TI  - Factors influencing repeated teenage pregnancy: a review and meta-analysis.
AB  - OBJECTIVE: Existing evidence of predictors of repeated teenage pregnancy has not
      been assessed rigorously. This systematic review provides a comprehensive
      evaluation of protective and risk factors that are associated with repeated
      teenage pregnancy through a metaanalytical consensus. DATA SOURCES: We used
      PubMed, EMBASE, CINAHL, ProQuest, PsychINFO, ScienceDirect, Scopus, and Web of
      Science databases from 1997-2015 and the reference list of other relevant
      research papers and related reviews. STUDY ELIGIBILITY CRITERIA: Eligibility
      criteria included (1) epidemiologic studies that analyzed factors associated with
      repeated pregnancy or birth among adolescents <20 years of age who were
      nulliparous or experienced at least 1 pregnancy, and (2) experimental studies
      with an observational component that was adjusted for the intervention. STUDY
      APPRAISAL AND SYNTHESIS METHODS: We performed narrative synthesis of study
      characteristics, participant characteristics, study results, and quality
      assessment. We also conducted random-effects and quality-effects metaanalyses
      with meta-regression to obtain pooled odds ratios of identified factors and to
      determine sources of between-study heterogeneity. RESULTS: Twenty-six eligible
      epidemiologic studies, most from the United States (n=24), showed >47 factors
      with no evidence of publication bias for each metaanalysis. Use of contraception
      (pooled odds ratio, 0.60; 95% confidence interval, 0.35-1.02), particularly long
      acting reversible contraceptives (pooled odds ratio, 0.19; 95% confidence
      interval, 0.08-0.45), considerably reduced repeated teenage pregnancy risk. Among
      studies about contraception, the number of follow-up visits (adjusted
      coefficient, 0.72; P=.102) and country of study (unadjusted coefficient, 2.57;
      permuted P=.071) explained between-study heterogeneity. Education-related
      factors, which included higher level of education (pooled odds ratio, 0.74; 95%
      confidence interval, 0.60-0.91) and school continuation (pooled odds ratio, 0.53;
      95% confidence interval, 0.33-0.84), were found to be protective. Conversely,
      depression (pooled odds ratio, 1.46; 95% confidence interval, 1.14-1.87), history
      of abortion (pooled odds ratio, 1.66; 95% confidence interval, 1.08-2.54), and
      relationship factors, such as partner support, increased the repeated teenage
      pregnancy risk. CONCLUSION: Contraceptive use, educational factors, depression,
      and a history of abortion are the highly influential predictors of repeated
      teenage pregnancy. However, there is a lack of epidemiologic studies in low- and
      middle-income countries to measure the extent and characteristics of repeated
      teenage pregnancy across more varied settings.

PMID- 28433735
TI  - Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy
      of unknown location.
AB  - BACKGROUND: Pregnancies of unknown location with abnormal beta-human chorionic
      gonadotropin trends are frequently treated as presumed ectopic pregnancies with
      methotrexate. Preliminary data suggest that outpatient endometrial aspiration may
      be an effective tool to diagnose pregnancy location, while also sparing women
      exposure to methotrexate. OBJECTIVE: The purpose of this study was to evaluate
      the utility of an endometrial sampling protocol for the diagnosis of pregnancies
      of unknown location after in vitro fertilization. STUDY DESIGN: A retrospective
      cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles
      from October 2007 to September 2015 was performed; 110 patients were diagnosed
      with pregnancy of unknown location, defined as a positive beta-human chorionic
      gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and
      an abnormal beta-human chorionic gonadotropin trend (<53% rise or <15% fall in 2
      days). These patients underwent outpatient endometrial sampling with Karman
      cannula aspiration. Patients with a beta-human chorionic gonadotropin decline
      >=15% within 24 hours of sampling and/or villi detected on pathologic analysis
      were diagnosed with failing intrauterine pregnancy and had weekly beta-human
      chorionic gonadotropin measurements thereafter. Those patients with beta-human
      chorionic gonadotropin declines <15% and no villi identified were diagnosed with
      ectopic pregnancy and treated with intramuscular methotrexate (50 mg/m2) or
      laparoscopy. RESULTS: Across 8 years of follow up, among women with pregnancy of
      unknown location, failed intrauterine pregnancy was diagnosed in 46 patients
      (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical
      variables that included fresh or frozen embryo transfer, day of embryo transfer,
      serum beta-human chorionic gonadotropin at the time of sampling, endometrial
      thickness, and presence of an adnexal mass were not significantly different
      between patients with failed intrauterine pregnancy or ectopic pregnancy. In
      patients with failed intrauterine pregnancy, 100% demonstrated adequate
      postsampling beta-human chorionic gonadotropin declines; villi were identified in
      just 46% (n=21 patients). Patients with failed intrauterine pregnancy had
      significantly shorter time to resolution (negative serum beta-human chorionic
      gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6
      vs 26.3 days; P<.001). CONCLUSION: With the use of this safe and effective
      protocol of endometrial aspiration with Karman cannula, a large proportion of
      women with pregnancy of unknown location are spared methotrexate, with a shorter
      time to pregnancy resolution than those who receive methotrexate.

PMID- 28433734
TI  - Prospective association of fetal liver blood flow at 30 weeks gestation with
      newborn adiposity.
AB  - BACKGROUND: The production of variation in adipose tissue accretion represents a
      key fetal adaptation to energy substrate availability during gestation. Because
      umbilical venous blood transports nutrient substrate from the maternal to the
      fetal compartment and because the fetal liver is the primary organ in which
      nutrient interconversion occurs, it has been proposed that variations in the
      relative distribution of umbilical venous blood flow shunting either through
      ductus venosus or perfusing the fetal liver represents a mechanism underlying
      this adaptation. OBJECTIVE: The objective of the present study was to determine
      whether fetal liver blood flow assessed before the period of maximal fetal fat
      deposition (ie, the third trimester of gestation) is prospectively associated
      with newborn adiposity. STUDY DESIGN: A prospective study was conducted in a
      cohort of 62 uncomplicated singleton pregnancies. Fetal ultrasonography was
      performed at 30 weeks gestation for conventional fetal biometry and
      characterization of fetal liver blood flow (quantified by subtracting ductus
      venosus flow from umbilical vein flow). Newborn body fat percentage was
      quantified by dual energy X-ray absorptiometry imaging at 25.8 +/- 3.3 (mean +/-
      standard error of the mean) postnatal days. Multiple regression analysis was used
      to determine the proportion of variation in newborn body fat percentage explained
      by fetal liver blood flow. Potential confounding factors included maternal age,
      parity, prepregnancy body mass index, gestational weight gain, gestational age at
      birth, infant sex, postnatal age at dual energy X-ray absorptiometry scan, and
      mode of infant feeding. RESULTS: Newborn body fat percentage was 13.5% +/- 2.4%
      (mean +/- standard error of the mean). Fetal liver blood flow at 30 weeks
      gestation was significantly and positively associated with newborn total fat mass
      (r=0.397; P<.001) and body fat percentage (r=0.369; P=.004), but not with lean
      mass (r=0.100; P=.441). After accounting for the effects of covariates, fetal
      liver blood flow explained 13.5% of the variance in newborn fat mass. The
      magnitude of this association was pronounced particularly in
      nonoverweight/nonobese mothers (prepregnancy body mass index, <25 kg/m2; n=36) in
      whom fetal liver blood flow explained 24.4% of the variation in newborn body fat
      percentage. CONCLUSION: Fetal liver blood flow at the beginning of the third
      trimester of gestation is associated positively with newborn adiposity,
      particularly among nonoverweight/nonobese mothers. This finding supports the role
      of fetal liver blood flow as a putative fetal adaptation underlying variation in
      adipose tissue accretion.

PMID- 28433736
TI  - On the role of the second-order derivative term in the calculation of convergent
      beam diffraction patterns.
AB  - The simulation of (scanning) transmission electron microscopy images and
      diffraction patterns is most often performed using the forward-scattering
      approximation where the second-order derivative term in z is assumed to be small
      with respect to the first-order derivative term in the modified Schrodinger
      equation. This assumption is very good at high incident electron energies, but
      breaks down at low energies. In order to study the differences between first- and
      second-order methods, convergent beam electron diffraction patterns were
      simulated for silicon at the [111] zone-axis orientation at 20 keV and compared
      using electron intensity difference maps and integrated intensity profiles. The
      geometrical differences in the calculated diffraction patterns could be explained
      by an Ewald surface analysis. Furthermore, it was found that solutions based on
      the second-order derivative equation contained small amplitude oscillations that
      need to be resolved in order to ensure numerical integration stability. This
      required the use of very small integration steps resulting in significantly
      increased computation time compared to the first-order differential equation
      solution. Lastly, the efficiency of the numerical integration technique is
      discussed.

PMID- 28433737
TI  - Exploring biochemical pathways for mono-ethylene glycol (MEG) synthesis from
      synthesis gas.
AB  - Mono-ethylene glycol (MEG) is an important petrochemical with widespread use in
      numerous consumer products. The current industrial MEG-production process relies
      on non-renewable fossil fuel-based feedstocks, such as petroleum, natural gas,
      and naphtha; hence, it is useful to explore alternative routes of MEG-synthesis
      from gases as they might provide a greener and more sustainable alternative to
      the current production methods. Technologies of synthetic biology and metabolic
      engineering of microorganisms can be deployed for the expression of new
      biochemical pathways for MEG-synthesis from gases, provided that such promising
      alternative routes are first identified. We used the BNICE.ch algorithm to
      develop novel and previously unknown biological pathways to MEG from synthesis
      gas by leveraging the Wood-Ljungdahl pathway of carbon fixation of acetogenic
      bacteria. We developed a set of useful pathway pruning and analysis criteria to
      systematically assess thousands of pathways generated by BNICE.ch. Published
      genome-scale models of Moorella thermoacetica and Clostridium ljungdahlii were
      used to perform the pathway yield calculations and in-depth analyses of seven (7)
      newly developed biological MEG-producing pathways from gases, including CO2, CO,
      and H2. These analyses helped identify not only better candidate pathways, but
      also superior chassis organisms that can be used for metabolic engineering of the
      candidate pathways. The pathway generation, pruning, and detailed analysis
      procedures described in this study can also be used to develop biochemical
      pathways for other commodity chemicals from gaseous substrates.

PMID- 28433738
TI  - Crimean-Congo hemorrhagic fever virus in ticks in Turkey: A broad range tick
      surveillance study.
AB  - In Turkey, Crimean-Congo hemorrhagic fever (CCHF) outbreaks started in northern
      regions in 2002. Human cases still continue to increase and the disease spreads
      in many other provinces of Turkey. The ecological role of the vector tick species
      occurring in Turkey is not certain exactly. Therefore, we planned a broad range
      tick study in three different ecological and geographical areas extending from
      the West Black Sea regions down to the Central Anatolia. The aim of this study
      was to determine and characterize CCHFV molecularly in feeding-ticks collected
      from various wild and domestic animals and from humans as well as in questing and
      unfed ticks. In this study, 4283 tick samples derived from 21 tick species were
      collected from 76 villages and 10 central districts in total. All tick pools were
      screened for the presence of CCHFV RNA by two nested RT-PCRs. PCR assays were
      positive for 27 (3.6%) of 736 pools. CCHFV was detected in Hyalomma marginatum,
      Dermacentor marginatus, Rhipicephalus bursa, Rhipicephalus turanicus, Hyalomma
      excavatum and Haemaphysalis parva pools. As a result of the phylogenetic
      analysis, it was determined that the obtained CCHFV sequences are clustered into
      Europe 1 clade. CCHFV was detected among ticks obtained from cattle, goats, wild
      boar, hare, and the ground. The presence of CCHFV in ticks obtained from various
      domestic and wild hosts and the nature, and thereby the distribution patterns of
      the virus in different ecological areas were presented in this study.
      Furthermore, CCHFV was also detected in unusual tick species. Consequently, these
      results indicate that tick surveillance studies in large-scale and wide varieties
      contribute to the ecology and epidemiology of CCHF in that region, and can be
      used as an early-warning system.

PMID- 28433739
TI  - Dual-functional drug liposomes in treatment of resistant cancers.
AB  - Efficacy of regular chemotherapy is significantly hampered by multidrug
      resistance (MDR) and severe systemic toxicity. The reduced toxicity has been
      evidenced after administration of drug liposomes, consisting of the first
      generation of regular drug liposomes, the second generation of long-circulation
      drug liposomes, and the third generation of targeting drug liposomes. However,
      MDR of cancers remains as an unsolved issue. The objective of this article is to
      review the dual-functional drug liposomes, which demonstrate the potential in
      overcoming MDR. Herein, dual-functional drug liposomes are referring to the drug
      containing phospholipid bilayer vesicles that possess a dual-function of
      providing the basic efficacy of drug and the extended effect of the drug carrier.
      They exhibit unique roles in treatment of resistant cancer via circumventing drug
      efflux caused by adenosine triphosphate binding cassette (ABC) transporters,
      eliminating cancer stem cells, destroying mitochondria, initiating apoptosis,
      regulating autophagy, destroying supply channels, utilizing microenvironment, and
      silencing genes of the resistant cancer. As the prospect of an estimation, dual
      functional drug liposomes would exhibit more strength in their extended function,
      hence deserving further investigation for clinical validation.

PMID- 28433740
TI  - Xenotransplantation of layer-by-layer encapsulated non-human primate islets with
      a specified immunosuppressive drug protocol.
AB  - Islet transplantation is as effective as but also less immunogenic than pancreas
      transplantation for the treatment of type 1 diabetes mellitus. However, as the
      complete elimination of immunogenicity still remains a major obstacle in islet
      transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using
      biocompatible polymers offers a rational approach to reducing host immune
      response towards transplanted islets. We investigated the effect of LbL of non
      human primate (NHP) islets on reducing immunogenicity as a preclinical model
      since NHPs have close phylogenetic and immunological relationship with humans.
      LbL with three-layers of polyethylene glycol (PEG) molecules (SH-6-arm-PEG-NHS, 6
      arm-PEG-catechol and linear PEG-SH) showed a uniform nano-shielding on islets
      without the loss of viability or function of islets. An immunosuppressive drug
      protocol was also combined to improve the survival rate of the transplanted
      islets in vivo. A xenorecipient (C57BL/6 mice) of LbL islet transplanted along
      with our immunosuppressive drug protocol showed 100% survival rate for 150days
      after transplantation. On the other hand, naked islet recipients showed poor
      survival time of 5.5+/-1.4days without drugs and 77.5+/-42days with the drug
      protocol. Immunohistochemistry of the transplanted grafts and serum cytokine
      concentration demonstrated less immunogenicity in the LbL islet transplanted
      recipients compared with the naked islet ones.

PMID- 28433742
TI  - Transposon-Mediated NLR Exile to the Pollen Allows Rice Blast Resistance without
      Yield Penalty.

PMID- 28433741
TI  - Loss of the neurodevelopmental gene Zswim6 alters striatal morphology and motor
      regulation.
AB  - The zinc-finger SWIM domain-containing protein 6 (ZSWIM6) is a protein of unknown
      function that has been associated with schizophrenia and limited educational
      attainment by three independent genome-wide association studies. Additionally, a
      putatively causal point mutation in ZSWIM6 has been identified in several cases
      of acromelic frontonasal dysostosis with severe intellectual disability. Despite
      the growing number of studies implicating ZSWIM6 as an important regulator of
      brain development, its role in this process has never been examined. Here, we
      report the generation of Zswim6 knockout mice and provide a detailed anatomical
      and behavioral characterization of the resulting phenotype. We show that Zswim6
      is initially expressed widely during embryonic brain development but becomes
      restricted to the striatum postnatally. Loss of Zswim6 causes a reduction in
      striatal volume and changes in medium spiny neuron morphology. These changes are
      associated with alterations in motor control, including hyperactivity, impaired
      rotarod performance, repetitive movements, and behavioral hyperresponsiveness to
      amphetamine. Together, our results show that Zswim6 is indispensable to normal
      brain function and support the notion that Zswim6 might serve as an important
      contributor to the pathogenesis of schizophrenia and other neurodevelopmental
      disorders.

PMID- 28433743
TI  - The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium
      species.
AB  - The genus Fusarium comprises many species, including Fusarium oxysporum, Fusarium
      solani, Fusarium graminearum and Fusarium verticillioides, and causes severe
      infections in plants and humans. In clinical settings, Fusarium is the third most
      frequent mould to cause invasive fungal infections after Aspergillus and the
      Mucorales. F. solani and F. oxysporum are the most prevalent Fusarium spp.
      causing clinical disease. However, few effective antifungal drugs are available
      to treat human and plant Fusarium infections. The cationic peptide antibiotic
      polymyxin B (PMB) exhibits antifungal activity against the human fungal pathogens
      Candida albicans and Cryptococcus neoformans, but its efficacy against Fusarium
      spp. is unknown. In this study, the antifungal activity of PMB was tested against
      12 Fusarium strains that infect humans and plants (banana, tomato, melon, pea,
      wheat and maize). PMB was fungicidal against all 12 Fusarium strains, with
      minimum fungicidal concentrations of 32 ug/mL or 64 ug/mL for most strains
      tested, as evidenced by broth dilution, methylene blue staining and XTT reduction
      assays. PMB can reduce the germination rates of conidia, but not chlamydospores,
      and can cause defects in cell membrane integrity in Fusarium strains. PMB
      exhibits synergistic activity with posaconazole and can potentiate the effect of
      fluconazole, voriconazole or amphotericin B against Fusarium spp. However, PMB
      does not show synergistic effects with fluconazole against Fusarium spp. as it
      does against Candida glabrata and C. neoformans, indicating evolutionary
      divergence of mechanisms between yeast pathogens and the filamentous fungus
      Fusarium.

PMID- 28433744
TI  - Emergence of the colistin resistance gene mcr-1 in Citrobacter freundii.

PMID- 28433745
TI  - Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral
      edema in mice.
AB  - High altitude cerebral edema (HACE) is a life-threatening illness that develops
      during the rapid ascent to high altitudes, but its underlying mechanisms remain
      unclear. Growing evidence has implicated inflammation in the susceptibility to
      and development of brain edema. In the present study, we investigated the
      inflammatory response and its roles in HACE in mice following high altitude
      hypoxic injury. We report that acute hypobaric hypoxia induced a slight
      inflammatory response or brain edema within 24h in mice. However, the
      lipopolysaccharide (LPS)-induced systemic inflammatory response rapidly
      aggravated brain edema upon acute hypobaric hypoxia exposure by disrupting blood
      brain barrier integrity and activating microglia, increasing water permeability
      via the accumulation of aquaporin-4 (AQP4), and eventually leading to impaired
      cognitive and motor function. These findings demonstrate that hypoxia augments
      LPS-induced inflammation and induces the occurrence and development of cerebral
      edema in mice at high altitude. Here, we provide new information on the impact of
      systemic inflammation on the susceptibility to and outcomes of HACE.

PMID- 28433746
TI  - Transforming growth factor-beta 1 signaling regulates neuroinflammation and
      apoptosis in mild traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) is a low-level injury, which often remains
      undiagnosed, and in most cases it leads to death and disability as it advances as
      secondary injury. Therefore, it is important to study the underlying signaling
      mechanisms of mTBI-associated neurological ailments. While transforming growth
      factor-beta1 (TGF-beta1) has a significant role in inflammation and apoptosis in
      myriads of other pathophysiological conditions, the precise function of increased
      TGF-beta1 after mTBI is unknown. In this study, our objective is to study the
      physiological relevance and associated mechanisms of TGF-beta1-mediated
      inflammation and apoptosis in mTBI. Using an in vitro stretch-injury model in rat
      neuronal cultures and the in vivo fluid percussion injury (FPI) model in rats, we
      explored the significance of TGF-beta1 activation in mTBI. Our study demonstrated
      that the activation of TGF-beta1 in mTBI correlated with the induction of free
      radical generating enzyme NADPH oxidase 1 (NOX1). Further, using TGF-beta type I
      receptor (TGF-betaRI) inhibitor SB431542 and transfection of TGF-beta1 siRNA and
      TGF-beta antagonist Smad7, we established the neuroinflammatory and apoptotic
      role of TGF-beta1 in mTBI. Inhibition of TGF-betaRI or TGF-beta1 diminished TGF
      beta1-induced inflammation and apoptosis. Further, the enhanced TGF-beta1
      activation increased the phosphorylation of R-Smads including Smad2 and Smad3
      proteins. By immunofluorescence, western blotting, ELISA and TUNEL experiments,
      we demonstrated the up-regulation of pro-inflammatory cytokines IL-1beta and TNF
      alpha and apoptotic cell death in neurons. In conclusion, this study could
      establish the significance of TGF-beta1 in transforming the pathophysiology of
      mTBI into secondary injury.

PMID- 28433747
TI  - Chemical composition of Ocimum sanctum by LC-ESI-MS/MS analysis and its
      protective effects against smoke induced lung and neuronal tissue damage in rats.
AB  - Smoke induced oxidative stress is known to cause various cancers and associated
      health problems including lung cancer. Herbal extracts have been reported as
      antioxidant supplements which attenuate free radical induced oxidative damage of
      tissues, among which Ocimum sanctum has been reported as the elixir of life due
      to its innumerable health benefits. In the present study, we investigated the
      protective effect of O. sanctum against cracker smoke induced lung and brain
      tissue damage. The results of the study demonstrate that O. sanctum regulates the
      hematological and serum biochemical parameters such as RBC, WBC, blood urea
      nitrogen and creatinine kinase. O. sanctum supplementation inhibited oxidative
      stress as analyzed by SOD, CAT enzyme levels and i-NOS, HSP-70 protein
      expression. O. sanctum administration also regulated neurotransmitter levels,
      such as serotonin, dopamine, and regulated acetylcholine esterase levels which
      play a vital role in neuronal function. Further O. sanctum treatment also
      preserved the morphology of lung and brain tissues of smoke stress induced rats
      as observed by histopathology and transmission electron microscope analysis. The
      biodistribution of O. sanctum was showed its accumulation in key tissues such as
      kidney, liver, lungs and heart. The LC-ESI-MS/MS analysis of O. sanctum showed
      the presence of polyphenols, flavonoids and fatty acids which might be
      responsible for the observed anti-stress effects.

PMID- 28433748
TI  - The repertoire of epithelial morphogenesis on display: Progressive elaboration of
      Drosophila egg structure.
AB  - Epithelial structures are foundational for tissue organization in all metazoans.
      Sheets of epithelial cells form lateral adhesive junctions and acquire apico
      basal polarity perpendicular to the surface of the sheet. Genetic analyses in the
      insect model, Drosophila melanogaster, have greatly advanced our understanding of
      how epithelial organization is established, and how it is modulated during tissue
      morphogenesis. Major insights into collective cell migrations have come from
      analyses of morphogenetic movements within the adult follicular epithelium that
      cooperates with female germ cells to build a mature egg. Epithelial follicle
      cells progress through tightly choreographed phases of proliferation, patterning,
      reorganization and migrations, before they differentiate to form the elaborate
      structures of the eggshell. Distinct structural domains are organized by
      differential adhesion, within which lateral junctions are remodeled to further
      shape the organized epithelia. During collective cell migrations, adhesive
      interactions mediate supracellular organization of planar polarized
      macromolecules, and facilitate crawling over the basement membrane or traction
      against adjacent cell surfaces. Comparative studies with other insects are
      revealing the diversification of morphogenetic movements for elaboration of
      epithelial structures. This review surveys the repertoire of follicle cell
      morphogenesis, to highlight the coordination of epithelial plasticity with
      progressive differentiation of a secretory epithelium. Technological advances
      will keep this tissue at the leading edge for interrogating the precise
      spatiotemporal regulation of normal epithelial reorganization events, and provide
      a framework for understanding pathological tissue dysplasia.

PMID- 28433749
TI  - Novel sulphur-containing imatinib metabolites found by untargeted LC-HRMS
      analysis.
AB  - Untargeted metabolite profiling using high-resolution mass spectrometry coupled
      with liquid chromatography (LC-HRMS), followed by data analysis with the Compound
      Discoverer 2.0TM software, was used to study the metabolism of imatinib in humans
      with chronic myeloid leukemia. Plasma samples from control (drug-free) and
      patient (treated with imatinib) groups were analyzed in full-scan mode and the
      unknown ions occurring only in the patient group were then, as potential imatinib
      metabolites, subjected to multi-stage fragmentation in order to elucidate their
      structure. The application of an untargeted approach, as described in this study,
      enabled the detection of 24 novel structurally unexpected metabolites. Several
      sulphur-containing compounds, probably originating after the reaction of reactive
      intermediates of imatinib with endogenous glutathione, were found and annotated
      as cysteine and cystine adducts. In the proposed mechanism, the cysteine adducts
      were formed after the rearrangement of piperazine moiety to imidazoline. On the
      contrary, in vivo S-N exchange occurred in the case of the cystine adducts. In
      addition, N-O exchange was observed in the collision cell in the course of the
      fragmentation of the cystine adducts. The presence of sulphur in the cysteine and
      cystine conjugates was proved by means of ultra-high resolution measurements
      using Orbitrap Elite. The detection of metabolites derived from glutathione might
      improve knowledge about the disposition of imatinib towards bioactivation and
      help to improve understanding of the mechanism of its hepatotoxicity or
      nephrotoxicity in humans.

PMID- 28433751
TI  - Elevated chaperone proteins are a feature of winter freeze avoidance by larvae of
      the goldenrod gall moth, Epiblema scudderiana.
AB  - Winter survival for many insect species includes a need to maintain metabolic
      homeostasis and structural/functional integrity of macromolecules not only over a
      wide range of cold temperatures but also in response to rapid temperature change.
      Chaperones are well-known to protect/stabilize protein structure with regard to
      heat stress but less is known about their potential involvement in long-term
      protection of the proteome at subzero temperatures. The present study assessed
      the participation of chaperone proteins in the cold hardiness of larvae of the
      goldenrod gall moth, Epiblema scudderiana (Clemens) (Lepidoptera, Olethreutidae),
      monitoring changes in nine proteins over the winter months as well as their
      responses to laboratory cold acclimation or anoxia exposure. Four heat shock
      proteins (HSPs: Hsp110, Hsp70, Hsp60, Hsp40), three glucose-regulated proteins
      (GRPs: Grp78, Grp 94, Grp170) and the tailless complex polypeptide 1 (TCP-1) as
      well as the heat shock transcription factor (HSF1) were investigated. In general,
      all were significantly elevated in larvae collected from an outdoor site between
      October and March, as compared with September values, and chaperone levels were
      reduced again in April. The October to March interval also includes the period of
      diapause followed by cold quiescence in the species. Relative expression of
      Hsp70, Hsp60 and Hsp40 rose by 2-3-fold, GRPs increased 1.5-3-fold, and levels of
      active (hyperphosphorylated) HSF1 increased by 4-4.8-fold over the midwinter
      months. Chilling from 15 degrees C to 4 degrees C in the laboratory upregulated
      Grp78 protein content that remained high as temperature was further reduced to -4
      degrees C and then -20 degrees C whereas Hsp110, Hsp70 and HSF1 levels increased
      when larvae were exposed to -4 degrees C and -20 degrees C. Grp170 (also known as
      oxygen-regulated protein 150) was the only chaperone that increased significantly
      in the larvae in response to anoxia exposure at 4 degrees C. The data also
      indicated that multiple subcellular compartments received enhanced protection for
      their proteome since upregulation of chaperones included proteins known to occur
      in cytosolic (Hsp40, Hsp70), mitochondrial (Hsp60) and endoplasmic reticulum
      (Grp170) locations. Overall, the data indicate that chaperones have a significant
      role to play in the winter cold hardiness of E. scudderiana and identify
      declining temperatures (and perhaps also oxygen restriction) as potential
      modulators of chaperone production. The data add support to a relatively
      understudied area of insect cold hardiness - the long-term protection and
      stabilization of the proteome over the winter months.

PMID- 28433750
TI  - Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of
      acetazolamide.
AB  - In the present work the antiglaucoma drug, acetazolamide, was formulated as an
      ion induced nanoemulsion-based in situ gel for ocular delivery aiming a sustained
      drug release and an improved therapeutic efficacy. Different acetazolamide loaded
      nanoemulsion formulations were prepared using peanut oil, tween 80 and/or
      cremophor EL as surfactant in addition to transcutol P or propylene glycol as
      cosurfactant. Based on physicochemical characterization, the nanoemulsion
      formulation containing mixed surfactants and transcutol P was selected to be
      incorporated into ion induced in situ gelling systems composed of gellan gum
      alone and in combination with xanthan gum, HPMC or carbopol. The nanoemulsion
      based in situ gels showed a significantly sustained drug release in comparison to
      the nanoemulsion. Gellan/xanthan and gellan/HPMC possessed good stability at all
      studied temperatures, but gellan/carbopol showed partial drug precipitation upon
      storage and was therefore excluded from the study. Gellan/xanthan and gellan/HPMC
      showed higher therapeutic efficacy and more prolonged intraocular pressure
      lowering effect relative to that of commercial eye drops and oral tablet.
      Gellan/xanthan showed superiority over gellan/HPMC in all studied parameters and
      is thus considered as a promising mucoadhesive nanoemulsion-based ion induced in
      situ gelling formula for topical administration of acetazolamide.

PMID- 28433752
TI  - Serotonergic transmission and gap junctional coupling in proventricular muscle
      cells in the American cockroach, Periplaneta americana.
AB  - The visceral muscle tissues of insects consist of striated muscle cells. The
      mechanisms responsible for delivering signals to the contractile muscles in the
      insect digestive tract remain unclear. We found that serotonergic nerves
      innervate the hemocoel surfaces of foregut and midgut muscles in the American
      cockroach. Electron microscopy of the neuromuscular junctions in the
      proventriculus (gizzard) revealed typical synaptic structures, the accumulation
      of large core/cored vesicles (neuropeptides) and small clear vesicle
      (neurotransmitter) at presynapses, and synaptic clefts. However, only a limited
      number of muscle cells, which were located in the outer part of the muscle layer,
      came into contact with synapses, which contained classical neurotransmitters,
      such as glutamate. A gap junction channel-permeable fluorescent dye, Lucifer
      yellow, was microinjected into single muscle cells, and it subsequently spread to
      several neighboring muscle cells. The dye movement occurred in the radial
      (hemocoel-lumen) direction rather than tangential directions. A gap junction
      blocker, octanol, reversibly inhibited the dye coupling. Messenger RNA for
      innexin 2, a gap junction-related protein, was detected in the proventriculus.
      These results suggest that motile signals in the insect digestive tract only
      reach the outermost part of the visceral muscles and are propagated to the inner
      muscle cells via gap junctions. Therefore, invertebrate gap junction-related
      proteins have potential as new targets for pest control.

PMID- 28433753
TI  - Computational image analysis for prognosis determination in DME.
AB  - In this pilot study, we evaluated the potential of computational image analysis
      of optical coherence tomography (OCT) data to determine the prognosis of patients
      with diabetic macular edema (DME). Spectral-domain OCT scans with fully automated
      retinal layer segmentation and segmentation of intraretinal cystoid fluid (IRC)
      and subretinal fluid of 629 patients receiving anti-vascular endothelial growth
      factor therapy for DME in a randomized prospective clinical trial were analyzed.
      The results were used to define 312 potentially predictive features at three
      timepoints (baseline, weeks 12 and 24) for best-corrected visual acuity (BCVA) at
      baseline and after one year used in a random forest prediction path.
      Preliminarily, IRC in the outer nuclear layer in the 3-mm area around the fovea
      seemed to have the greatest predictive value for BCVA at baseline, and IRC and
      the total retinal thickness in the 3-mm area at weeks 12 and 24 for BCVA after
      one year. The overall model accuracy was R2=0.21/0.23 (p<0.001). The outcomes of
      this pilot analysis highlight the great potential of the proposed machine
      learning approach for large-scale image data analysis in DME and other retinal
      diseases.

PMID- 28433755
TI  - Response to letter to the editor on the article "Impact on the upper airway space
      of different types of orthognathic surgery for the correction of skeletal class
      III malocclusion: A systematic review and meta-analysis".

PMID- 28433754
TI  - miR-146a suppresses STAT3/VEGF pathways and reduces apoptosis through IL-6
      signaling in primary human retinal microvascular endothelial cells in high
      glucose conditions.
AB  - microRNA (miRNA) play critical roles in the pathological processes of diabetic
      retinopathy, including inflammatory responses, insulin signaling, and
      angiogenesis. In addition to their regulatory functions on gene expression, miRNA
      is considered as a potential therapeutic target, as well as a diagnostic marker
      for many diseases. Our understanding on the pathological mechanisms underlying
      diabetic retinopathy is still incomplete and additional investigations are
      required to develop novel therapeutic strategies. The aim of this study was to
      investigate our hypothesis that miR-146a plays a role in suppressing pro
      inflammatory pathways, involving STAT3 and VEGF, through regulating IL-6
      signaling to reduce apoptosis of human retinal endothelial cells (REC) in high
      glucose conditions. Human REC were cultured in normal (5mM) glucose or high
      glucose medium (25mM) for 3days. We performed transfections on REC with miRNA
      mimics (hsa-miR-146a-5p). Overexpression of miR-146a reduced IL-6 levels, STAT3
      phosphorylation, and VEGF levels in REC cultured in high glucose. Cellular
      apoptosis was decreased in REC overexpressing miR-146a, as demonstrated by the
      inhibition of DNA fragmentation. More importantly, we demonstrated that the
      regulatory role of miR-146a on STAT3/VEGF and apoptosis was mediated by IL-6
      receptor signaling in REC. Overall, we report that miR-146a suppressed IL-6
      signaling, leading to reduced levels of STAT3 and VEGF in REC in high glucose
      conditions, leading to decreased apoptosis. The outcome suggests that miR-146a is
      a potential molecular target for inhibiting inflammation and apoptosis in the
      diabetic retina through the suppression of the IL-6-mediated STAT3/VEGF pathway.

PMID- 28433756
TI  - Letter to the editor on the article "Impact on the upper airway space of
      different types of orthognathic surgery for the correction of skeletal class III
      malocclusion: A systematic review and meta-analysis".

PMID- 28433757
TI  - Surgical volunteerism or voluntourism - Are we doing more harm than good?
AB  - The significant rise in the number of international health electives undertaken
      by medical students and doctors in the US, Canada and UK reflects acknowledgement
      of the inter-connected nature of these challenges to health systems and the drive
      to help solve them. However, the next generation of international volunteers
      often operate under a conflicting duality: whilst many of their role models have
      devoted their lives to global health following a similar volunteering experience,
      there are pervasive ethical problems associated with transient global health work
      that must be identified and addressed to ensure positive outcomes for all parties
      involved. The majority of populations served by shortterm surgical volunteer
      trips are vulnerable communities; this raises ethical questions such as the lack
      of informed consent, use of unauthorised photos for marketing, and practicing new
      procedural techniques. 2 Whilst there exist various models that can be used to
      facilitate effective international health electives, there is a lack of stringent
      monitoring and enforcement both on the part of healthcare institutions deploying
      volunteers as well as recipient bodies in LMICS. Well-organised programmes
      prevent cases of 'poor care given to poor people' as medical students and doctors
      are expected to act in their patients' best interests as they would do in their
      home country. As clinician interest in global health projects continue to rise,
      too-common trainee naivety - while rooted in goodwill - must be supplanted by
      adequate training, ethical coherence, and cultural fluency. The onus lies on
      medical schools and healthcare bodies endorsing international electives to ensure
      that individuals are appropriately prepared and only travel through programmes
      that are able to demonstrate that they meet the necessary requirements and follow
      guidelines to avoid doing more harm than good.

PMID- 28433758
TI  - Osteomicrobiology: The influence of gut microbiota on bone in health and disease.

PMID- 28433759
TI  - Reverse shoulder arthroplasty combined with latissimus dorsi transfer: A systemic
      review.
AB  - : Reverse shoulder arthroplasty (RSA) combined with latissimus dorsi transfer
      (LDT) is described for patients with cuff arthropathy and a combined loss of
      abduction and external rotation. The purpose of this systemic review was to
      present clinical and radiological outcomes following RSA combined with LDT. A
      comprehensive literature review was performed to identify studies reporting
      clinical and radiological results of RSA combined with LDT. Seven articles that
      describe the treatment of 116 patients were selected. Functional scores, range of
      motion, radiological outcome, complications, rehabilitation regime, surgical
      technique, patient demographics and indication were analyzed and discussed. All
      studies reported significant improvement in functional scores and abduction and
      external rotation. Complications occurred in 26% of patients. Although high-level
      studies are lacking, this systemic review shows that RSA combined with LDT is a
      reliable surgical method with which to treat patients with loss of active
      abduction and loss of external rotation. The available data are insufficient to
      draw conclusions regarding the long-term outcomes of this procedure. LEVEL OF
      EVIDENCE: IV.

PMID- 28433760
TI  - Elucidation of the dynamic nature of interactome networks: A practical tutorial.
AB  - : Considering that proteins are usually engaged in complex and dynamic networks
      of interactions to exert their activity, a way to understand proteins' functions
      and the molecular mechanisms in which those proteins are involved, is by studying
      their interactome. In this sense, this tutorial presents a simple pipeline for
      the analysis of the network of interactions of a protein in order to reach a
      biological interpretation of the mechanisms modulated by those interactions, and
      to understand how these interactions are affected by the experimental conditions.
      The entire pipeline is explained using as example the previously published work
      "Interacting network of the gap junction protein connexin43 is modulated by
      ischemia and reperfusion in the heart", and by using user-friendly and freely
      available software. Moreover, the pipeline presented in this article is not
      limited to interactomic approaches, being also useful for the analysis of dynamic
      alterations of other proteomic screenings. SIGNIFICANCE: This tutorial presents a
      simplified pipeline for the analysis of the network of interactions of a protein
      in order to reach to a biological interpretation of the mechanisms modulated by
      those interactions, which constitutes an important way to understand proteins'
      functions and the molecular mechanisms in which those proteins are involved.
      Moreover, when interactomics is applied to perform an in-depth molecular analysis
      of novel disease proteins, it can result in an understanding of disease-causing
      mechanisms and create drug discovery opportunities. Nevertheless, the pipeline
      presented can be also useful for the analysis of dynamic alterations of other
      biomolecules.

PMID- 28433761
TI  - A glycoproteomic approach reveals that the S-layer glycoprotein of Lactobacillus
      kefiri CIDCA 83111 is O- and N-glycosylated.
AB  - : In Gram-positive bacteria, such as lactic acid bacteria, general glycosylation
      systems have not been documented so far. The aim of this work was to characterize
      in detail the glycosylation of the S-layer protein of Lactobacillus kefiri CIDCA
      83111. A reductive beta-elimination treatment followed by anion exchange high
      performance liquid chromatography analysis was useful to characterize the O
      glycosidic structures. MALDI-TOF mass spectrometry analysis confirmed the
      presence of oligosaccharides bearing from 5 to 8 glucose units carrying
      galacturonic acid. Further nanoHPLC-ESI analysis of the glycopeptides showed two
      O-glycosylated peptides: the peptide sequence SSASSASSA already identified as a
      signature glycosylation motif in L. buchneri, substituted on average with eight
      glucose residues and decorated with galacturonic acid and another O-glycosylated
      site on peptide 471-476, with a Glc5-8GalA2 structure. As ten characteristic
      sequons (Asn-X-Ser/Thr) are present in the S-layer amino acid sequence, we
      performed a PNGase F digestion to release N-linked oligosaccharides. Anion
      exchange chromatography analysis showed mainly short N-linked chains. NanoHPLC
      ESI in the positive and negative ion modes were useful to determine two different
      peptides substituted with short N-glycan structures. To our knowledge, this is
      the first description of the structure of N-glycans in S-layer glycoproteins from
      Lactobacillus species. SIGNIFICANCE: A detailed characterization of protein
      glycosylation is essential to establish the basis for understanding and
      investigating its biological role. It is known that S-layer proteins from kefir
      isolated L. kefiri strains are involved in the interaction of bacterial cells
      with yeasts present in kefir grains and are also capable to antagonize the
      adverse effects of different enteric pathogens. Therefore, characterization of
      type and site of glycosidic chains in this protein may help to understand these
      important properties. Furthermore, this is the first description of N-glycosidic
      chains in S-layer glycoprotein from Lactobacillus spp.

PMID- 28433762
TI  - Novel viral and host targets to cure hepatitis B.
AB  - Hepatitis B virus (HBV) infection is a global health threat with 240 million
      chronic carriers at high risk to develop hepatocellular carcinoma. Current
      antiviral treatment can efficiently control viral replication and reduce liver
      inflammation, but is still quite far from achieving a cure. Significant progress
      has been made in understanding the virus life cycle and virus-host interaction in
      the past few years. With identification of the HBV receptor, cell-culture
      infection systems have become available that allow drug screening and
      establishing a pipeline of potential antivirals targeting either viral or host
      factors. Most of the candidate antivirals summarized in this review are still in
      preclinical development, but some have already entered or are about to enter
      early clinical trials.

PMID- 28433763
TI  - Biomass burning sources and their contributions to the local air quality in Hong
      Kong.
AB  - In this paper, we present a quantitative estimation of the impacts of biomass
      burning emissions from different source regions to the local air quality in Hong
      Kong in 2014 using global chemistry transport model simulations, sun photometer
      measurements, satellite observations and local monitoring network data. This
      study focuses on two major biomass burning pollutants, black carbon aerosols and
      carbon monoxide (CO). The model simulations of atmospheric black carbon and CO
      show excellent agreement with sun photometer aerosol optical depth (AOD)
      measurements, satellite CO columns observations and local monitoring stations
      data. From the model simulation results, we estimated that biomass burning
      contributes 12% of total black carbon and 16% of atmospheric CO in Hong Kong on
      annual average. South East Asia shows the largest influence to the black carbon
      and CO levels in Hong Kong, accounts for 11% of the total atmospheric black
      carbon and 8% of CO. Biomass burning in North East Asia and Africa also show
      significant impacts to Hong Kong. Elevated levels of atmospheric black carbon
      aerosols and CO were observed during springtime (March and April) which is mainly
      due to the enhancement of biomass burning contributions. Black carbon and CO
      originating from biomass burning sources are estimated to contribute 40% of
      atmospheric black carbon and 28% of CO in Hong Kong during March 2014. An
      investigation focusing on the biomass burning pollution episode during springtime
      suggests the intensified biomass burning activities in the Indochinese Peninsula
      are the major sources of black carbon and CO in Hong Kong during the time.

PMID- 28433764
TI  - Modeling of retention and re-entrainment of mono- and poly-disperse particles:
      Effects of hydrodynamics, particle size and interplay of different-sized
      particles retention.
AB  - In this paper, numerical simulations of experimental data were performed with
      kinetic rate coefficients to characterize the retention and re-entrainment
      dynamics under different hydrodynamic conditions for monodisperse and
      polydisperse latex particles (3, 10, 16MUm and the mixture). The results show
      that drastic increase in fluid velocity provokes hardly any remarkable decrease
      in retention in the presence of large energy barriers (>2000kT). Systematical
      increases in deposition and re-entrainment dynamic rates were observed with fluid
      velocity and/or particle size. Increased irreversible deposition rate indicates
      straining and wedging dominate deposition in this study. Excess retention of 3MUm
      particle in the polydisperse particle suspension was observed. The origins are
      reckoned that deposited larger particles may hinder the re-entrainment of smaller
      particles near the grain-to-grain contact and can provide additional sites of
      attachment.

PMID- 28433765
TI  - Geochemical processes controlling the distribution and concentration of metals in
      soils from a Patagonian (Argentina) salt marsh affected by mining residues.
AB  - Heavy metal pollution that affects salt marshes is a major environmental concern
      due to its toxic nature, persistence, and potential risk to organisms and to
      human health. Mining waste deposits originated four decades ago, by the
      metallurgical extraction of heavy metals, are found near to the San Antonio salt
      marsh in Patagonia. The aim of the work was to determine the geochemical
      processes that control the distribution and concentration of Cu, Fe, Pb and Zn in
      the soils of this Patagonian salt marsh. A survey of the mining waste deposits
      was carried out where three dumps were identified. Samples were collected to
      determine soil texture, Eh pH, organic matter and metal contents and the soil
      mineralogical composition. The results shows that the soils developed over the
      mining waste deposits are predominantly reddish constituted mainly by iron oxide,
      hydroxide and highly soluble minerals such as Zn and Cu sulphates. The drainage
      from these deposits tends to move towards the salt marsh. Within the salt marsh,
      the highest concentrations of Cu, Pb and Zn occur in the sectors closest to the
      mining wastes deposits. The sulphide oxidation and the dissolution of the Cu, Pb
      and Zn sulphates could be the mainly source of these metals in the drainage
      water. The metals in solution that reach the salt marsh, are adsorbed by the
      organic matter and the fine fraction of the soils. These adsorbed metals are then
      remobilized by tides in the lower sectors of the marsh by desorption from the
      cations present in the tidal flow. On the other hand, Fe tends to form non
      soluble oxides, hydroxides and sulphates which remain as altering material within
      the mining waste deposit. Finally, the heavy metal pollutants recorded in the San
      Antonio salt marsh shows that the mining waste deposits that were abandoned four
      decades ago are still a source metal contamination.

PMID- 28433767
TI  - Temporal dynamics of human-excreted pollutants in wastewater treatment plant
      influents: Toward a better knowledge of mass load fluctuations.
AB  - The occurrence of 25 drug target residues (illicit drugs or pharmaceutically
      active compounds) was investigated during 85 consecutive days in the influents of
      a wastewater treatment plant in the Region Centre-Val de Loire, France. This long
      tracking period allowed a better understanding of the patterns affecting the
      occurrence of this type of contaminants. Among them, 2 were never detected (i.e.
      heroin and amphetamine). Concerning illicit drugs two patterns were found.
      Cocaine and ecstasy median loads varied considerably between weekdays and weekend
      days (i.e. 18.3 and 35.9% respectively) whereas cannabis and heroin (based on 6
      mono-acetylmorphine loads) loads were within the same order of magnitude with a
      significant statistical correlation with pharmaceuticals such as acetaminophen or
      ketoprofen. The consumption of selected drugs was back-calculated from the loads.
      Among illicit drugs the highest consumption was found for cannabis with a median
      consumption of 51mg.day-1.inhabitant-1 (inh) whereas the median consumption for
      cocaine (based on benzoylecgonine loads) and ecstasy was 32 and 6mg.day-1.103.inh
      1 respectively. The highest consumption values of pharmaceutically active
      compounds (PACs) were found for acetaminophen and acetylsalicylic acid with 108.8
      and 34.1mg.day-1.inh-1 respectively, in good agreement with national sales data.
      A statistically significant weekly pattern was found for several PACs such as
      metoprolol and trimethoprim, but with the opposite pattern to that of illicit
      drugs. The variations in daily PAC loads could provide information about the
      mobility of people in the catchment, especially on the basis of daily taken PACs
      (i.e. to treat chronicle diseases).

PMID- 28433766
TI  - 1,4-Dioxane drinking water occurrence data from the third unregulated contaminant
      monitoring rule.
AB  - This study examined data collected from U.S. public drinking water supplies in
      support of the recently-completed third round of the Unregulated Contaminant
      Monitoring Rule (UCMR3) to better understand the nature and occurrence of 1,4
      dioxane and the basis for establishing drinking water standards. The purpose was
      to evaluate whether the occurrence data for this emerging but federally
      unregulated contaminant fit with common conceptual models, including its
      persistence and the importance of groundwater contamination for potential
      exposure. 1,4-Dioxane was detected in samples from 21% of 4864 PWSs, and was in
      exceedance of the health-based reference concentration (0.35MUg/L) at 6.9% of
      these systems. In both measures, it ranked second among the 28 UCMR3
      contaminants. Although much of the focus on 1,4-dioxane has been its role as a
      groundwater contaminant, the detection frequency for 1,4-dioxane in surface water
      was only marginally lower than in groundwater (by a factor of 1.25; p<0.0001).
      However, groundwater concentrations were higher than those in surface water
      (p<0.0001) and contributed to a higher frequency of exceeding the reference
      concentration (by a factor of 1.8, p<0.0001), indicating that surface water
      sources tend to be more dilute. Sampling from large systems increased the
      likelihood that 1,4-dioxane was detected by a factor of 2.18 times relative to
      small systems (p<0.0001). 1,4-Dioxane detections in drinking water were highly
      associated with detections of other chlorinated compounds particularly 1,1
      dichlorethane (odds ratio=47; p<0.0001), which is associated with the release of
      1,4-dioxane as a chlorinated solvent stabilizer. Based on aggregated nationwide
      data, 1,4-dioxane showed evidence of a decreasing trend in concentration and
      detection frequency over time. These data suggest that the loading to drinking
      water supplies may be decreasing. However, in the interim, some water supply
      systems may need to consider improving their treatment capabilities in response
      to further regulatory review of this compound.

PMID- 28433768
TI  - Response of evapotranspiration to changes in land use and land cover and climate
      in China during 2001-2013.
AB  - Land surface evapotranspiration (ET) is a central component of the Earth's global
      energy balance and water cycle. Understanding ET is important in quantifying the
      impacts of human influences on the hydrological cycle and thus helps improving
      water use efficiency and strengthening water use planning and watershed
      management. China has experienced tremendous land use and land cover changes
      (LUCC) as a result of urbanization and ecological restoration under a broad
      background of climate change. This study used MODIS data products to analyze how
      LUCC and climate change affected ET in China in the period 2001-2013. We examined
      the separate contribution to the estimated ET changes by combining LUCC and
      climate data. Results showed that the average annual ET in China decreased at a
      rate of -0.6mm/yr from 2001 to 2013. Areas in which ET decreased significantly
      were mainly distributed in the northwest China, the central of southwest China,
      and most regions of south central and east China. The trends of four climatic
      factors including air temperature, wind speed, sunshine duration, and relative
      humidity were determined, while the contributions of these four factors to ET
      were quantified by combining the ET and climate datasets. Among the four climatic
      factors, sunshine duration and wind speed had the greatest influence on ET. LUCC
      data from 2001 to 2013 showed that forests, grasslands and croplands in China
      mutually replaced each other. The reduction of forests had much greater effects
      on ET than change by other land cover types. Finally, through quantitative
      separation of the distinct effects of climate change and LUCC on ET, we conclude
      that climate change was the more significant than LULC change in influencing ET
      in China during the period 2001-2013. Effective water resource management and
      vegetation-based ecological restoration efforts in China must consider the
      effects of climate change on ET and water availability.

PMID- 28433769
TI  - Healing activity evaluation of the galactomannan film obtained from Cassia
      grandis seeds with immobilized Cratylia mollis seed lectin.
AB  - Galactomannan films from Cassia grandis seeds, associated or not with Cramoll
      1,4, were used on topical wounds of rats for the evaluation of the healing
      process during 14days. All of the films were evaluated by cytotoxic assay, FTIR
      and lectin hemagglutinating activity (HA). Forty-five male rats were submitted to
      aseptic dermal wounds (O=0.8cm) and divided in groups (n=15): control, test 1,
      and test 2, treated respectively with saline, galactomannan film and film with
      immobilized Cramoll 1,4. Macroscopic evaluations were performed by clinical
      observations and area measurements, and microscopic analysis by histological
      criteria. Epithelial cell proliferation and differentiation was
      immunohistochemically assessed using CK14 and PCNA. The presence of CO peaks in
      the FTIR spectrum confirmed the immobilization of Cramoll 1,4 in the film, while
      the residual HA confirmed the stability of the lectin after immobilization with
      90.94% of the initial HA. The films presented non-cytotoxicity and cell viability
      exceeding 80%. All of the animals presented re-epithelization around 10days,
      furthermore test 2 group showed a diffuse response at the stromal tissue and the
      basal layer associated with wounds completely closed with 11days of experiment.
      The results suggest a promising use of the films as topical wound curatives.

PMID- 28433770
TI  - Preparation of low digestible and viscoelastic tigernut (Cyperus esculentus)
      starch by Bacillus acidopullulyticus pullulanase.
AB  - Tigernut starch is an underutilized food resource. In this study, pullulanase
      (PUL) hydrolysis was used to change its physiochemical properties for different
      food applications. The content of low digestible fractions, resistant starch and
      slow digestible starch, in PUL modified tigernut starch significantly increased
      from 2.03% to 25.08% (P<0.05) using 100U/g starch of PUL in the debranching
      reaction. The paste or dispersion of PUL modified tigernut starch had a
      significantly decreased viscoelasticity (P<0.05), but the paste still exhibited a
      typical property of pseudoplasticity. Molecular weight, amylopectin A B2 and B3
      chain of PUL modified starch were lower, while amylose content, amylopectin B1
      chain were higher than those of natural tigernut starch. The low digestible and
      viscous tigernut starch is highly valued as a component in some functional foods.

PMID- 28433771
TI  - A Versatile Tumor Gene Deletion System Reveals a Crucial Role for FGFR1 in Breast
      Cancer Metastasis.
AB  - RCAS avian viruses have been used to deliver oncogene expression and induce
      tumors in transgenic mice expressing the virus receptor TVA. Here we report the
      generation and characterization of a novel RCAS-Cre-IRES-PyMT (RCI-PyMT) virus
      designed to specifically knockout genes of interest in tumors generated in
      appropriate mutant mouse hosts. FGF receptor 1 (FGFR1) is a gene that is
      amplified in human breast cancer, but there have been no definitive studies on
      its function in mammary tumorigenesis, progression, and metastasis in vivo in
      spontaneous tumors in mice. We used the retroviral tumor knockout, or TuKO,
      strategy to delete fgfr1 in PyMT-induced mammary tumors in K19-tva/fgfr1loxP/loxP
      mice. The similarly injected control K19-tva mice developed mammary tumors
      exhibiting high metastasis to lung, making this an ideal model for breast cancer
      metastasis. The fgfr1 TuKO tumors showed significantly decreased primary tumor
      growth and, most importantly, greatly reduced metastasis to lung. In contrast to
      previous reports, FGFR1 action in this spontaneous mammary tumor model does not
      significantly induce epithelial-to-mesenchymal transition. Loss of FGFR1 does
      generate a gene signature that is reverse correlated with FGFR1 gene
      amplification and/or upregulation in human breast cancer. Our results suggest
      that FGFR1 signaling is a key pathway driving breast cancer lung metastasis and
      that targeting FGFR1 in breast cancer is an exciting approach to inhibit
      metastasis.

PMID- 28433773
TI  - Who's calling? Social networks and mobile phone use among motorcyclists.
AB  - Mobile phone use while riding a motorcycle poses a key safety risk, particularly
      among younger people who have been found to be more susceptible to distracted
      driving. While previous research has examined the influence of social networks on
      mobile phone use while driving a car, no research has explored this association
      in the context of motorcycle use. Using a survey of university students in
      Vietnam, this research explores the association between social networks and
      mobile phone use among motorcyclists and the links this has to reported
      crashes/falls. Results show that the majority of students are most likely to use
      a mobile phone to communicate with a friend while riding, either through talking
      (56.5%) or text messaging (62.0%). However, respondents who frequently talk to a
      girlfriend/boyfriend or spouse while riding were more likely to experience a
      crash/fall than those who frequently talk with others while riding (e.g. parent,
      brother/sister). In addition, those who frequently text message a friend while
      riding were more likely to experience a crash/fall than those who frequently text
      message others while riding. The results highlight a clear association between
      social networks and mobile phone use while riding a motorcycle. Developing a
      culture of societal norms, where mobile phone use while riding a motorcycle is
      considered socially unacceptable, will help to reduce the prevalence and ultimate
      crash risk associated with mobile phone use while riding.

PMID- 28433772
TI  - Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon
      Cancer Cells through Direct Cell-to-Cell Contact.
AB  - We previously reported that in an orthotopic nude mouse model of human colon
      cancer, bone marrow-derived mesenchymal stem cells (MSCs) migrated to the tumor
      stroma and promoted tumor growth and metastasis. Here, we evaluated the
      proliferation and migration ability of cancer cells cocultured with MSCs to
      elucidate the mechanism of interaction between cancer cells and MSCs.
      Proliferation and migration of cancer cells increased following direct coculture
      with MSCs but not following indirect coculture. Thus, we hypothesized that direct
      contact between cancer cells and MSCs was important. We performed a microarray
      analysis of gene expression in KM12SM colon cancer cells directly cocultured with
      MSCs. Expression of epithelial-mesenchymal transition (EMT)-related genes such as
      fibronectin (FN), SPARC, and galectin 1 was increased by direct coculture with
      MSCs. We also confirmed the upregulation of these genes with real-time polymerase
      chain reaction. Gene expression was not elevated in cancer cells indirectly
      cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture
      with MSCs, we examined the immune localization of FN, a well-known EMT marker. In
      coculture assay in chamber slides, expression of FN was seen only at the edges of
      cancer clusters where cancer cells directly contacted MSCs. FN expression in
      cancer cells increased at the tumor periphery and invasive edge in orthotopic
      nude mouse tumors and human colon cancer tissues. These results suggest that MSCs
      induce EMT in colon cancer cells via direct cell-to-cell contact and may play an
      important role in colon cancer metastasis.

PMID- 28433774
TI  - The role of Compensatory Health Beliefs in eating behavior change: A mixed method
      study.
AB  - Compensatory Health Beliefs (CHBs), defined as beliefs that an unhealthy behavior
      can be compensated for by engaging in another healthy behavior, are assumed to
      hinder health behavior change. The aim of the present study was to investigate
      the role of CHBs for two distinct eating behaviors (increased fruit and vegetable
      consumption and eating fewer unhealthy snacks) with a mixed method approach.
      Participants (N = 232, mean age = 27.3 years, 76.3% women) were randomly assigned
      to a fruit and vegetable or an unhealthy snack condition. For the quantitative
      approach, path models were fitted to analyze the role of CHBs within a social
      cognitive theory of health behavior change, the Health Action Process Approach
      (HAPA). With a content analysis, the qualitative approach investigated the
      occurrence of CHBs in smartphone chat groups when pursuing an eating goal. Both
      analyses were conducted for each eating behavior separately. Path models showed
      that CHBs added predictive value for intention, but not behavior over and above
      HAPA variables only in the unhealthy snack condition. CHBs were significantly
      negatively associated with intention and action planning. Content analysis
      revealed that people generated only a few CHB messages. However, CHBs were more
      likely to be present and were also more diverse in the unhealthy snack condition
      compared to the fruit and vegetable condition. Based on a mixed method approach,
      this study suggests that CHBs play a more important role for eating unhealthy
      snacks than for fruit and vegetable consumption.

PMID- 28433775
TI  - Looking is buying. How visual attention and choice are affected by consumer
      preferences and properties of the supermarket shelf.
AB  - There is a battle in the supermarket isle, a battle between what the consumer
      wants and what the retailer and others want her to see, and subsequently to buy.
      Product packages and displays contain a number of features and attributes
      tailored to catch consumers' attention. These are what we call external factors
      comprising the visual saliency, the number of facings, and the placement of each
      product. But a consumer also brings with her a number of goals and interests
      related to the products and their attributes. These are important internal
      factors, including brand preferences, price sensitivity, and dietary
      inclinations. We fit mobile eye trackers to consumers visiting real-life
      supermarkets in order to investigate to what extent external and internal factors
      affect consumers' visual attention and purchases. Both external and internal
      factors influenced what products consumers looked at, with a strong positive
      interaction between visual saliency and consumer preferences. Consumers appear to
      take advantage of visual saliency in their decision making, using their knowledge
      about products' appearance to guide their visual attention towards those that fit
      their preferences. When it comes to actual purchases, however, visual attention
      was by far the most important predictor, even after controlling for all other
      internal and external factors. In other words, the very act of looking longer or
      repeatedly at a package, for any reason, makes it more likely that this product
      will be bought. Visual attention is thus crucial for understanding consumer
      behaviour, even in the cluttered supermarket environment, but it cannot be
      captured by measurements of visual saliency alone.

PMID- 28433776
TI  - Increasing water intake in pre-school children with unhealthy drinking habits: A
      year-long controlled longitudinal field experiment assessing the impact of
      information, water affordance, and social regulation.
AB  - OBJECTIVE: We investigated the effect of three interventions to increase the
      plain water consumption of children with unhealthy drinking habits, with an
      innovative approach combining the three layers of Installation Theory: embodied
      competences, affordances and social regulation. METHODS: 334 preschool children
      and their carers were allocated to three interventions: Control (control): no
      intervention, Information (info): online coaching sessions on water health
      benefits aiming at modifying embodied competences (knowledge), Information +
      Water Affordance (info + w): the same plus home delivery of small bottles of
      water. After three months, half of the info and info + w subjects were allocated
      to Social Regulation (+social) (on-line discussion forum) or no further
      intervention (-social). Intake of plain water and all other fluid types of the
      children were recorded by the carers 6 times over a year using an online 7-day
      fluid-specific dietary record. RESULTS: Over 1 year, all groups significantly
      increased daily water consumption by 3.0-7.8 times (+118 to +222 mL). Info + w +
      social and Info-social generated the highest increase in plain water intake after
      one year compared to baseline, by 7.8 times (+216 mL) and 6.7 times (+222 mL)
      respectively; both significantly exceeded the control (3.0 times, +118 mL),
      whilst the effect of info + w-social (5.0 times, +158 mL) and info + social (5.3
      times, +198 mL) did not differ from that of control. All groups saw a decrease of
      sweetened beverages intake, again with info + w + social generating the largest
      decrease (-27%; -172 mL). No changes in other fluids or total fluid intake were
      observed. CONCLUSIONS: Sustainable increased water consumption can be achieved in
      children with unhealthy drinking habits by influencing representations, changing
      material affordances, and providing social regulation. Combining the three
      provided the strongest effect as predicted by Installation Theory.

PMID- 28433777
TI  - Design and expeditious synthesis of organosilanes as potent antivirals targeting
      multidrug-resistant influenza A viruses.
AB  - The efficacy of current influenza vaccines and small molecule antiviral drugs is
      curtailed by the emerging of multidrug-resistant influenza viruses. As resistance
      to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu),
      continues to rise, there is a clear need to develop the next-generation of
      antiviral drugs. Since more than 95% of current circulating influenza A viruses
      carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel
      represents an attractive target for the development of broad-spectrum antivirals.
      In this study we report the design and synthesis of the first class of
      organosilanes that have potent antiviral activity against a panel of human
      clinical isolates of influenza A viruses, including viruses that are resistant to
      amantadine, oseltamivir, or both.

PMID- 28433778
TI  - Novel lipid-mimetic prodrugs delivering active compounds to adipose tissue.
AB  - Obesity and associated pathologies are a dramatically growing problem. New
      therapies to prevent and/or cure them are strongly needed. Adipose tissue is a
      logical target for pharmacological intervention, since it is now recognized to
      exert an important endocrine function, secreting a variety of adipokines
      affecting, for example, adiposity and insulin resistance. This proof of principle
      work focuses on the development of novel lipid-mimetic prodrugs reaching fat
      deposits by the same lymphatic absorption route followed by dietary
      triglycerides. Pterostilbene, a natural phenolic compound with potential anti
      obesity effects, was used as model "cargo", attached via a carbamate group to an
      omega-aminodecanoate chain linked to either position 1 or position 2 of the
      glycerol moiety of synthetic triglycerides. The prodrugs underwent position
      selective hydrolysis when challenged with pancreatic lipases in vitro.
      Pterostilbene-containing triglycerides as well as pterostilbene and its
      metabolites were present in the adipose tissue of mice fed an obesogenic diet
      containing one or the other of the derivatives. For the first time this approach
      is used to deliver an obesity antagonist to the adipose tissue. The results
      demonstrate the feasibility of delivering active compounds to adipose tissue by
      reversibly incorporating them into triglyceride-mimetic structures. Upon release
      in the target site these compounds are expected to exert their pharmacological
      activity precisely where needed.

PMID- 28433780
TI  - The Impact of Family History on the Risk of Colorectal Neoplasia and Screening
      Practices.

PMID- 28433779
TI  - Identification of new anti-inflammatory agents based on nitrosporeusine natural
      products of marine origin.
AB  - Nitrosporeusines A and B are two recently isolated marine natural products with
      novel skeleton and exceptional biological profile. Interesting antiviral activity
      of nitrosporeusines and promising potential in curing various diseases, evident
      from positive data from various animal models, led us to investigate their anti
      inflammatory potential. Accordingly, we planned and synthesized nitrosporeusines
      A and B in racemic as well as enantiopure forms. The natural product synthesis
      was followed by preparation of several analogues, and all the synthesized
      compounds were evaluated for in vitro and in vivo anti-inflammatory potential.
      Among them, compounds 25, 29 and 40 significantly reduced levels of nitric oxide
      (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines. In addition,
      these compounds suppressed several pro-inflammatory mediators including inducible
      nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF
      kappaB), and thereby can be emerged as potent anti-inflammatory compounds.
      Furthermore, all possible isomers of lead compound 25 were synthesized,
      characterized and profiled in same set of assays and found that one of the
      enantiomer (-)-25a was superior among them.

PMID- 28433782
TI  - Dietary Recommendations for Ulcerative Colitis Remain a Mystery.

PMID- 28433781
TI  - Prevalence of Celiac Disease Autoimmunity Among Adolescents and Young Adults in
      China.
AB  - BACKGROUND & AIMS: In China, epidemiologic information on celiac disease
      autoimmunity is scarce and fragmented. We investigated the prevalence of celiac
      disease autoimmunity in the general Chinese population. METHODS: In a cross
      sectional prospective study, 19,778 undiagnosed Chinese adolescents and young
      adults (age, 16-25 y) were recruited from consecutive new students who underwent
      routine physical examinations at 2 universities in Jiangxi, China, from September
      2010 through October 2013; the students were from 27 geographic regions in China.
      All subjects were tested for serum IgG, IgG against deamidated gliadin peptides
      (IgG anti-DGP), and IgA anti-tissue transglutaminase antibodies (IgA anti-tTG).
      We also analyzed HLA genotypes in subgroups of participants with different
      results from tests for serum markers of celiac disease. RESULTS: A total of 434
      students (2.19%) tested positive for serum markers for celiac disease (95%
      confidence interval [CI], 1.99%-2.41%), 0.36% of the students tested positive for
      anti-tTG IgA (95% CI, 0.28%-0.46%), and 1.88% tested positive for anti-DGP IgG
      (95% CI, 1.70%-2.09%). The prevalence of celiac disease autoimmunity (positive
      results in assays for anti-tTG IgA and anti-DGP-IgG) was 0.06% (95% CI, 0.03%
      0.10%). Celiac disease autoimmunity was associated with the consumption of wheat
      and female sex. The prevalence in the Shandong province in north China, where
      wheat is a staple in the diet, was 0.76% (95% CI, 0.21%-1.95%). The frequencies
      of the HLA-DQ2/-DQ8 genotypes associated with celiac disease were higher in
      subjects with celiac disease autoimmunity, based on detection of both serum
      markers, than in subjects with positive results from a single test (P < .01). All
      subjects with positive results from both assays carried the HLA-DQ2 genotype.
      CONCLUSIONS: Approximately 2% of adolescents or young adults in China had
      positive results from assays for serum markers for celiac disease. The prevalence
      of celiac disease autoimmunity in the Shandong province in north China, where
      wheat is a staple in the diet, was 0.76%.

PMID- 28433783
TI  - Efficacy of Balloon Overtube-Assisted Colonoscopy in Patients With Incomplete or
      Previous Difficult Colonoscopies: A Meta-analysis.

PMID- 28433784
TI  - Needle Tract Tumor Seeding Following Endoscopic Ultrasound-Guided Fine Needle
      Aspiration of Metastatic Squamous Cell Carcinoma.

PMID- 28433785
TI  - Barriers and motivations for non-invasive drug delivery.

PMID- 28433786
TI  - Mucoadhesive tetrahydrocannabinol-loaded NLC - Formulation optimization and long
      term physicochemical stability.
AB  - Tetrahydrocannabinol (THC) is used to treat pain in cancer patients. On the
      market there are mainly oral formulations. Especially to treat the problematic
      breakthrough pain in cancer, an easy applicable formulation with fast onset is
      desired. This formulation was developed as an aqueous nasal spray using
      nanostructured lipid carriers (NLC). The NLC were prepared with cetyl palmitate,
      having good miscibility with the oily THC and yielding particles with 1year
      physical long-term stability. To make the particles mucoadhesive, small particles
      with diameters of about 200nm were produced and additionally their surface
      positively charged using a cationic stabilizer. Optimal NLC suspensions contained
      1% particles (lipid:THC ratio 7:1) stabilized with 0.05% cetylpyridinium chloride
      (CPC), and 2% particles with a mixture of 0.05% CPC, and 0.05% Tween(r) 80. The
      particle size remained unchanged during spraying using commercial spray bottle,
      and PARI BOY. A strong interaction with negatively charged mucin was shown by a
      sharp decrease of the positive NLC zeta potential and fast charge reversal in the
      mucin solution test. The solid matrix of the NLC had a stabilizing effect on THC.
      91% THC remained after 6months storage at 4 degrees C, and 79% under stress
      conditions at 40 degrees C. By adding additional chemical stabilizers, and
      producing under protective conditions, a commercial formulation for patient seems
      feasible.

PMID- 28433787
TI  - Facile encapsulation of hydroxycamptothecin nanocrystals into zein-based
      nanocomplexes for active targeting in drug delivery and cell imaging.
AB  - : Nano-drug delivery systems that integrate inorganic and organic or even
      bioactive components into a single nanoscale platform are playing a hugely
      important role in cancer treatment. In this article, the fabrication of a
      versatile nanocarrier based on self-assembled structures of gold nanoparticles
      (AuNPs)-zein is reported, which displays high drug-loading efficiency for needle
      shaped hydroxycamptothecin (HCPT) nanocrystals. The surface modification with
      folate-conjugated polydopamine (PFA) renders them stable and also facilitates
      their selective cellular internalization and enhancement of endocytosis. The
      release of payloads from nanocomplexes (NCs) was shown to be limited at
      physiological pH (17.1+/-2.8%) but significantly elevated at endosomal/lysosomal
      pH (58.4+/-3.0%) and at enzymatic environment (81.4+/-4.2%). Compared to free
      HCPT and its non-targeting equivalent, HCPT@AuNPs-Zein-PFA exerted a superior
      tumor suppression capacity as well as low side effects due to its active and
      passive targeting delivery both in vitro and in vivo. These results suggest that
      the NCs with well-defined core@shell nanostructures encapsulated with HCPT
      nanocrystals hold great promise to improve cancer therapy with high efficiency in
      the clinic. STATEMENT OF SIGNIFICANCE: A novel nanocomplex with HCPT nanocrystals
      encapsulated was designed to achieve selective cellular uptake by endocytosis,
      acid responsive release in the tumor microenvironment and excellent tumor
      suppression without toxicity. This nanocomplex with conjugation of folate was
      stable in the bloodstream, with minimal drug release in extracellular conditions,
      leading to prolonged blood circulation and high accumulation in tumor tissues.
      The entrapment of a nanocrystal drug into nanomaterials might be capable of
      delivering drugs in a predictable and controllable manner.

PMID- 28433789
TI  - Macromolecular crowding for tailoring tissue-derived fibrillated matrices.
AB  - : Tissue-derived fibrillated matrices can be instrumental for the in vitro
      reconstitution of multiphasic extracellular microenvironments. However, despite
      of several advantages, the obtained scaffolds so far offer a rather narrow range
      of materials characteristics only. In this work, we demonstrate how
      macromolecular crowding (MMC) - the supplementation of matrix reconstitution
      media with synthetic or natural macromolecules in ways to create excluded volume
      effects (EVE) - can be employed for tailoring important structural and
      biophysical characteristics of kidney-derived fibrillated matrices. Porcine
      kidneys were decellularized, ground and the obtained extracellular matrix (ECM)
      preparations were reconstituted under varied MMC conditions. We show that MMC
      strongly influences the fibrillogenesis kinetics and impacts the architecture and
      the elastic modulus of the reconstituted matrices, with diameters and relative
      alignment of fibrils increasing at elevated concentrations of the crowding agent
      Ficoll400, a nonionic synthetic polymer of sucrose. Furthermore, we demonstrate
      how MMC modulates the distribution of key ECM molecules within the reconstituted
      matrix scaffolds. As a proof of concept, we compared different variants of kidney
      derived fibrillated matrices in cell culture experiments referring to specific
      requirements of kidney tissue engineering approaches. The results revealed that
      MMC-tailored matrices support the morphogenesis of human umbilical vein
      endothelial cells (HUVECs) into capillary networks and of murine kidney stem
      cells (KSCs) into highly branched aggregates. The established methodology is
      concluded to provide generally applicable new options for tailoring tissue
      specific multiphasic matrices in vitro. STATEMENT OF SIGNIFICANCE: Tissue-derived
      fibrillated matrices can be instrumental for the in vitro reconstitution of
      multiphasic extracellular microenvironments. However, despite of several
      advantages, the obtained scaffolds so far offer a rather narrow range of
      materials characteristics only. Using the kidney matrix as a model, we herein
      report a new approach for tailoring tissue-derived fibrillated matrices by means
      of macromolecular crowding (MMC), the supplementation of reconstitution media
      with synthetic or natural macromolecules. MMC-modulation of matrix reconstitution
      is demonstrated to allow for the adjustment of fibrillation kinetics and nano
      architecture, fiber diameter, alignment, and matrix elasticity. Primary human
      umbilical vein endothelial cells (HUVEC) and murine kidney stem cells (KSC) were
      cultured within different variants of fibrillated kidney matrix scaffolds. The
      results showed that MMC-tailored matrices were superior in supporting desired
      morphogenesis phenomena of both cell types.

PMID- 28433788
TI  - Regulation of human nucleus pulposus cells by peptide-coupled substrates.
AB  - : Nucleus pulposus (NP) cells are derived from the notochord and differ from
      neighboring cells of the intervertebral disc in phenotypic marker expression and
      morphology. Adult human NP cells lose this phenotype and morphology with age in a
      pattern that contributes to progressive disc degeneration and pathology. Select
      laminin-mimetic peptide ligands and substrate stiffnesses were examined for their
      ability to regulate human NP cell phenotype and biosynthesis through the
      expression of NP-specific markers aggrecan, N-cadherin, collagen types I and II,
      and GLUT1. Peptide-conjugated substrates demonstrated an ability to promote
      expression of healthy NP-specific markers, as well as increased biosynthetic
      activity. We show an ability to re-express markers of the juvenile NP cell and
      morphology through control of peptide presentation and stiffness on well
      characterized polyacrylamide substrates. NP cells cultured on surfaces conjugated
      with alpha3 integrin receptor peptides P4 and P678, and on alpha2, alpha5,
      alpha6, beta1 integrin-recognizing peptide AG10, show increased expression of
      aggrecan, N-cadherin, and types I and II collagen, suggesting a healthier, more
      juvenile-like phenotype. Multi-cell cluster formation was also observed to be
      more prominent on peptide-conjugated substrates. These findings indicate a
      critical role for cell-matrix interactions with specific ECM-mimetic peptides in
      supporting and maintaining a healthy NP cell phenotype and bioactivity. STATEMENT
      OF SIGNIFICANCE: NP cells reside in a laminin-rich environment that deteriorates
      with age, including a loss of water content and changes in the extracellular
      matrix (ECM) structure that may lead to the development of a degenerated IVD.
      There is great interest in methods to re-express healthy, biosynthetically active
      NP cells using laminin-derived biomimetic peptides toward the goal of using
      autologous cell sources for tissue regeneration. Here, we describe a novel study
      utilizing several laminin mimetic peptides conjugated to polyacrylamide gels that
      are able to support an immature, healthy NP phenotype after culture on "soft"
      peptide gels. These findings can support future studies in tissue regeneration
      where cells may be directed to a desired regenerative phenotype using niche
      specific ECM peptides.

PMID- 28433790
TI  - A strain-mediated corrosion model for bioabsorbable metallic stents.
AB  - : This paper presents a strain-mediated phenomenological corrosion model, based
      on the discrete finite element modelling method which was developed for use with
      the ANSYS Implicit finite element code. The corrosion model was calibrated from
      experimental data and used to simulate the corrosion performance of a WE43
      magnesium alloy stent. The model was found to be capable of predicting the
      experimentally observed plastic strain-mediated mass loss profile. The non-linear
      plastic strain model, extrapolated from the experimental data, was also found to
      adequately capture the corrosion-induced reduction in the radial stiffness of the
      stent over time. The model developed will help direct future design efforts
      towards the minimisation of plastic strain during device manufacture, deployment
      and in-service, in order to reduce corrosion rates and prolong the mechanical
      integrity of magnesium devices. STATEMENT OF SIGNIFICANCE: The need for corrosion
      models that explore the interaction of strain with corrosion damage has been
      recognised as one of the current challenges in degradable material modelling
      (Gastaldi et al., 2011). A finite element based plastic strain-mediated
      phenomenological corrosion model was developed in this work and was calibrated
      based on the results of the corrosion experiments. It was found to be capable of
      predicting the experimentally observed plastic strain-mediated mass loss profile
      and the corrosion-induced reduction in the radial stiffness of the stent over
      time. To the author's knowledge, the results presented here represent the first
      experimental calibration of a plastic strain-mediated corrosion model of a
      corroding magnesium stent.

PMID- 28433791
TI  - Employment and choice-making for adults with intellectual disability, autism, and
      down syndrome.
AB  - BACKGROUND: Adults with disabilities are employed at a significantly lower rate
      than adults without disabilities. Of adults with disabilities in the workforce,
      more individuals work in a facility setting rather than a community setting,
      despite efforts to improve community inclusion. Choice-making has been proposed
      as a predictive factor for employment for individuals with disabilities. AIMS:
      The purpose of this research was to examine the current state of employment for
      three groups of adults with intellectual disability (ID): individuals with autism
      spectrum disorder (ASD), individuals with Down syndrome (DS), and individuals
      with idiopathic ID. Choice-making and its relation to improved employment
      outcomes was explored. METHODS: This study used National Core Indicator's Adult
      Consumer Survey datasets from years 2011-2012 and 2012-2013. Factor analyses
      revealed latent variables from six choice-making questions in the Adult Consumer
      Survey. Ordinal logistic regression was used to identify factors related to
      employment status. RESULTS: Adults with DS had the highest rates of paid
      community jobs, but adults with ID had the highest rates of choice-making. ID
      severity level and short-term choice-making had the greatest effects on
      employment status in all three groups. CONCLUSIONS: Employment rates remain low
      despite national efforts to find jobs for people with disabilities. Choice-making
      is a unique factor that was found to be associated with employment status and
      provides a target for interventions to increase employability.

PMID- 28433792
TI  - A Pilot Study Examining a Computer-Based Intervention to Improve Recognition and
      Understanding of Emotions in Young Children with Communication and Social
      Deficits.
AB  - BACKGROUND: A common social impairment in individuals with ASD is difficulty
      interpreting and or predicting emotions of others. To date, several interventions
      targeting teaching emotion recognition and understanding have been utilized both
      by researchers and practitioners. The results suggest that teaching emotion
      recognition is possible, but that the results do not generalize to non
      instructional contexts. This study sought to replicate earlier findings of a
      positive impact of teaching emotion recognition using a computer-based
      intervention and to extend it by testing for generalization on live models in the
      classroom setting. METHOD: Two boys and one girl, four to eight years in age,
      educated in self-contained classrooms for students with communication and social
      skills deficits, participated in this study. A multiple probe across participants
      design was utilized. Measures of emotion recognition and understanding were
      assessed at baseline, intervention, and one month post-intervention to determine
      maintenance effects. Social validity was assessed through parent and teacher
      questionnaires. RESULTS: All participants showed improvements in measures
      assessing their recognition of emotions in faces, generalized knowledge to live
      models, and maintained gains one month post intervention. CONCLUSIONS: These
      preliminary results are encouraging and should be utilized to inform a group
      design, in order to test efficacy with a larger population.

PMID- 28433793
TI  - What does handedness reveal about ADHD? An analysis based on CPT performance.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a developmental
      disorder. Continuous performance Tests (CPTs) aid the diagnosis. Handedness is
      linked to disabilities. OBJECTIVES: 1-To study the association between handedness
      and ADHD; 2-To verify the usefulness of the CPT in school settings; 3-To exam the
      relationship between handedness and CPT performance. METHOD: Each child was
      classified as right-consistent, left-consistent, or non-consistent. From the
      sample, 171 controls and 68 ADHDs fulfilled the inclusion criteria. The effect of
      handedness on the CPT was studied using a paired-sample that matched handedness
      by age, grade, gender, and ADHD. RESULTS: Left-handed students had a probability
      of suffering from ADHD 2.88 greater than right-handers. ANOVAs on standardized
      scores indicated that the ADHD students exhibited higher number of errors and
      higher variability of reaction times as compared to the controls. Discriminant
      analysis indicated that these CPT parameters could discriminate ADHD from
      controls. Repeated ANOVAs showed a significant effect of handedness on commission
      errors (CE) because left-handers made more CEs than right-handers. CONCLUSIONS: 1
      The association between ADHD and handedness reflects that left-handers are less
      lateralized and have decreased interhemispheric connections; 2-The CPT can be
      used to measure different attention domains in school settings; 3- Left-handers
      have problems in the impulsive/hyperactivity domain.

PMID- 28433794
TI  - Detection of melanoma metastases with PET-Comparison of 18F-5-FPN with 18F-FDG.
AB  - INTRODUCTION: 18F-5-fluoro-N-(2-(Diethylamino)ethyl)picolinamide (18F-5-FPN) is a
      new positron-emission tomography (PET) radiopharmaceutical with potential for the
      detection of lymph node (LN) and pulmonary metastatic lesions of melanoma. We
      compared its performance with that of 18F-deoxyglucose (18F-FDG). METHODS:
      Cervical LN and lung melanoma metastasis models were established in C57BL/6 mice.
      Primary tumors were created by injection of melanoma cells into the pinna, and
      the resulting cervical LN metastases were evaluated. Lung metastases were created
      by intravenous injection of melanoma cells. The mice underwent 18F-FDG and 18F-5
      FPN positron emission tomography (PET) imaging. A biodistribution study was
      conducted after imaging. Histopathologic evaluation of the tumors was also
      performed. RESULTS: LN metastases with a diameter<1cm were more visible on 18F-5
      FPN PET imaging than 18F-FDG imaging. Quantitative analysis showed that the
      uptake of 18F-5-FPN was significantly higher than that of 18F-FDG, with values of
      13.29+/-3.80% ID/g and 7.24+/-1.95% ID/g (n=5, P<0.05), respectively. LN-to
      muscle ratios were 21.23+/-6.02 and 4.50+/-2.11 (n=5, P<0.01) for 18F-5-FPN and
      18F-FDG, respectively. Biodistribution results were similar, with high uptake of
      18F-5-FPN in the LN. 18F-5-FPN imaging manifested the pulmonary lesions clearly,
      while the 18F-FDG imaging showed no uptake in lesions <2mm. The related uptakes
      of 18F-5-FPN and 18F-FDG were 3.12+/-1.17% ID/g and 1.48+/-0.15% ID/g,
      respectively (n=5, P<0.05), with lung metastasis-to-muscle ratios of 8.16+/-3.12
      and 1.28+/-0.18 (n=5, P<0.01), respectively. H&E and Prussian blue staining
      displayed pluri nucleated or mega nucleus cells and dark brown granules in the
      metastatic tissues, characteristic of melanoma. CONCLUSIONS: 18F-5-FPN targeted
      small metastatic lesions with a higher target-to-normal ratio of uptake than
      those of 18F-FDG, which suggests its ability to detect metastatic lesions earlier
      than 18F-FDG. Further studies with a wide range of melanoma cell lines should be
      needed to confirm the similar performance.

PMID- 28433795
TI  - Helicobacter pylori cagL amino acid polymorphism D58E59 pave the way toward
      peptic ulcer disease while N58E59 is associated with gastric cancer in north of
      Iran.
AB  - The cagL protein of Helicobacter pylori involving in pathogenesis of
      gastroduodenal disorders. Therefore, the current study was conducted to determine
      the cagL amino acid polymorphisms in patients with gastric diseases. One hundred
      gastric biopsies were collected from gastritis, peptic ulcer (PUD) and gastric
      cancer (GC) patients and were screened for cagL using polymerase chain reaction
      (PCR). Also, sequence variations of the cagL were assessed via sequence
      translation. The cagL geneopositivity was 71.6% in patients were infected with H.
      pylori. The cagL from PUD indicated a higher rate of D58 amino acid sequence
      polymorphism than those of the GC and gastritis (P < 0.05). The D58 polymorphism
      showed an increased risk of PUD up to 6.5-fold (95% CI: 1.2-35.7). This position
      was occupied with amino acid N58 in GC. The E59 polymorphism was more frequently
      found in PUD and GC than gastritis patients. Additionally, presence of Q62 and
      N122 significantly observed in PUD and GC, whereas I60 was detected in PUD
      patients. Our results demonstrated that presence of the D, I, Q and N at position
      58, 60, 62 and 122, respectively increased the risk of peptic ulcer. However,
      amino acid N, M, Q and N at the same position alongside V134 increased the risk
      of gastric cancer.

PMID- 28433796
TI  - Genetic diversity and virulence genes of Salmonella enterica subspecies enterica
      serotype Enteritidis isolated from meats and eggs.
AB  - Salmonella enterica subspecies enterica serotype Enteritidis (S. Enteritidis) is
      one of the leading causes of food-borne gastroenteritis associated with the
      consumption of contaminated food products of animal origin. Little is known about
      the genetic diversity and virulence content of S. Enteritidis isolated from
      poultry meats and eggs in Iran. A total of 34 S. Enteritidis strains were
      collected from different food sources of animal origin in Tehran from May 2015 to
      July 2016. All of the S. Enteritidis strains were serotyped, antimicrobial
      susceptibility tested, and characterized for virulence genes. Pulsed-field gel
      electrophoresis (PFGE) was also applied for comparison of genetic relatedness.
      All of the strains harbored invA, hilA, ssrA, sefA, spvC, and sipA genes. A high
      prevalence of resistance against certain antibiotics such as cefuroxime (79.4%),
      nalidixic acid (47%), and ciprofloxacin (44.2%) was also observed. Regarding
      PFGE, S. Enteritidis strains from different sources showed considerable overlap,
      suggesting the lack of diversity among these isolates. Moreover, no correlation
      between virulence profiles or antibiotypes and PFGE clusters was observed. In
      conclusion, our study provided valuable information on virulence gene content,
      antibiotic resistance, and genetic diversity of S. Enteritidis isolated from food
      sources.

PMID- 28433797
TI  - Development of comorbid crying, sleeping, feeding problems across infancy:
      Neurodevelopmental vulnerability and parenting.
AB  - BACKGROUND: Regulatory problems (excessive crying, feeding, and sleeping
      difficulties), specifically their comorbidity, are early warning signs of future
      problems. Insensitive parenting and neurodevelopmental vulnerabilities have been
      suggested as factors explaining development or maintenance of regulatory
      problems. Nevertheless, none of the previous studies investigated these factors
      within the same sample across infancy, taking into account the reciprocal
      influences between maternal sensitivity and regulatory problems. AIM: To
      investigate the prospective association between very preterm birth, comorbid
      regulatory problems and maternal sensitivity. SUBJECTS: 178 participants
      including 73 very preterm/very low birth weight and 105 full-term infants and
      their caretakers. STUDY DESIGN: A prospective study from birth to 18months.
      MEASURES: Regulatory problems were measured at term, 3months and 18months with a
      structured parental interview. Maternal sensitivity was measured with a nurse
      observation at term; and a researcher observation of play tasks at 3months and at
      18months. RESULTS: Very preterm birth was associated with regulatory problems at
      term (beta=0.19, SE=0.10, p<0.05) and at 18months (beta=0.21, SE=0.10, p<0.05),
      while it had no association to maternal sensitivity across infancy. There were no
      cross-lagged reciprocal effects between maternal sensitivity and regulatory
      problems across infancy. Maternal sensitivity at term had a negative association
      to regulatory problems at 3months (beta=-0.26, SE=0.12, p<0.05), but not from 3
      to 18months. CONCLUSIONS: Neurodevelopmental vulnerabilities provided more
      consistent prediction of regulatory problems in comparison to sensitive
      parenting.

PMID- 28433798
TI  - Randomized trial of early erythropoietin supplementation after preterm birth:
      Iron metabolism and outcome.
AB  - BACKGROUND: Excess of iron and oxidant injury shortly after birth may be
      associated with neonatal morbidities in preterm infants. AIMS: The aim was to
      determine whether administration of erythropoietin without iron supplementation
      decreases iron load and morbidity. STUDY DESIGN AND SUBJECTS: In a randomized
      trial, we administered erythropoietin (EPO 250IU/kg daily during the first 6days
      of life) or placebo to 39 preterm infants (BW 700-1500g, GA<=30.0weeks). OUTCOME
      MEASURES: The iron status, postnatal morbidities and follow-up at the age of two
      years were investigated. RESULTS: In all, 21 EPO- and 18 placebo-treated infants
      were recruited. A requirement of red blood cell transfusions during first 28days
      was similar between the study groups. EPO treatment decreased total serum iron
      concentration (p=0.035). EPO supplementation had no significant effect on serum
      transferrin receptors or reactive non-protein-bound iron. There were no
      differences in neonatal morbidity or in survival without major neurological
      abnormality at two years of age. CONCLUSIONS: A 6-day course of EPO decreased the
      iron load in preterm infants. There was no change in reactive, non-protein bound
      iron plasma levels and no influence on the outcomes during early childhood.
      Whether the neurocognitive effects of early EPO treatment can be detectable later
      in childhood remained to be verified.

PMID- 28433799
TI  - Affinity Proteomics Exploration of Melanoma Identifies Proteins in Serum with
      Associations to T-Stage and Recurrence.
AB  - BACKGROUND: Blood-based proteomic profiling may aid and expand our understanding
      of diseases and their different phenotypes. The aim of the presented study was to
      profile serum samples from patients with malignant melanoma using affinity
      proteomic assays to describe proteins in the blood stream that are associated to
      stage or recurrence of melanoma. MATERIAL AND METHODS: Multiplexed protein
      analysis was conducted using antibody suspension bead arrays. A total of 232
      antibodies against 132 proteins were selected from (i) a screening with 4595
      antibodies and 32 serum samples from melanoma patients and controls, (ii)
      antibodies used for immunohistochemistry, (iii) protein targets previously
      related with melanoma. The analysis was performed with 149 serum samples from
      patients with malignant melanoma. Antibody selectivity was then assessed by
      Western blot, immunocapture mass spectrometry, and epitope mapping. Lastly,
      indicative antibodies were applied for IHC analysis of melanoma tissues. RESULTS:
      Serum levels of regucalcin (RGN) and syntaxin 7 (STX7) were found to be lower in
      patients with both recurring tumors and a high Breslow's thickness (T-stage 3/4)
      compared to low thickness (T-stage 1/2) without disease recurrence. Serum levels
      of methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) were instead elevated
      in sera of T3/4 patients with recurrence. The analysis of tissue sections with
      S100A6 and MTHFD1L showed positive staining in a majority of patients with
      melanoma, and S100A6 was significantly associated to T-stage. CONCLUSIONS: Our
      findings provide a starting point to further study RGN, STX7, MTHFD1L and S100A6
      in serum to elucidate their involvement in melanoma progression and to assess a
      possible contribution to support clinical indications.

PMID- 28433800
TI  - Chromosomal Alterations and Gene Expression Changes Associated with the
      Progression of Leukoplakia to Advanced Gingivobuccal Cancer.
AB  - We present an integrative genome-wide analysis that can be used to predict the
      risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC)
      arising in the gingivobuccal complex (GBC). We find that the genomic and
      transcriptomic profiles of leukoplakia resemble those observed in later stages of
      OSCC and that several changes are associated with this progression, including
      amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2,
      ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of
      primary tumors with and without lymph-node metastasis, we identify alterations
      associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1,
      11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers
      that have never or rarely been reported in previous OSCC studies, including
      amplifications of 1p36.33 (attributable to MXRA8), 3q26.31 (EIF5A2), 9p24.1
      (CD274), and 12q13.2 (HOXC9 and HOXC13). Additionally, we find that
      amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical
      outcome. Overall, our findings delineate genomic changes that can be used in
      treatment management for patients with potentially malignant leukoplakia and OSCC
      patients with higher risk of lymph-node metastasis.

PMID- 28433801
TI  - Moderate within-person variability in cortisol is related to executive function
      in early childhood.
AB  - Lab-based experimental studies with humans and in animal models demonstrate that
      the relation between glucocorticoid (GC) levels and performance on measures of
      higher-order cognitive ability such as executive function (EF) is best described
      by an inverted U-shape curve. Moderate levels of GCs (cortisol/corticosterone)
      are associated with comparatively better performance relative to GC levels that
      are particularly high or low. Although findings from experimental studies are
      definitive and have high internal validity, the external validity of this
      association as an aspect of children's development is unknown. Here we analyze
      data from the Family Life Project (N=1292), a prospective longitudinal sample of
      children and families in predominantly low-income and rural communities followed
      longitudinally from infancy through age 60 months. Consistent with the prior
      experimental literature, we found evidence of an inverted-U relation. For
      children with relatively low cortisol levels, on average, between the ages 7, 15,
      24, and 48 months, those illustrating moderate fluctuations in their cortisol
      levels over this span tended to show subsequently better EF performance at 60
      months, than did children with either highly stable or highly variable temporal
      profiles. This curvilinear function did not extend to children whose cortisol
      levels were high, on average. These children tended to show lower EF performance,
      irrespective the stability of their cortisol levels over time.

PMID- 28433803
TI  - Colorimetric and fluorimetric response of salicylaldehyde dithiosemicarbazone
      towards fluoride, cyanide and copper ions: Spectroscopic and TD-DFT studies.
AB  - The sensing mechanism of salicylaldehyde phenyldithiosemicarbazone (SDTSC)
      chemosensor has been investigated by spectroscopic and TD-DFT methods. The SDTSC
      shows colourimetric and spectral changes towards fluoride, cyanide and copper
      ions. The interaction between SDTSC with fluoride, cyanide and copper ions was
      examined through their absorption and fluorescence behaviour, and found that
      SDTSC has more sensing ability towards Cu2+ ion than CN- and F- ions. The 1H NMR
      titration with SDTSC and F- gives the structural changes in the sensing process.
      The reversibility of SDTSC was also evaluated and thus it is confirmed as a
      reusable chemosensor which can be clarified by the "Read-Erase-Read-Write" logic
      system. The DFT and TD-DFT calculations give the detailed sensing mechanism of
      SDTSC towards fluoride ion. The potential energy surface (PES) analysis confirms
      the excited state electron transfer mechanism.

PMID- 28433802
TI  - Role of environmental stressors in determining the developmental outcome of
      neonatal anesthesia.
AB  - BACKGROUND: The majority of studies evaluating neurocognition in humans who had
      procedures under anesthesia early in life found long-term deficits even though
      the typical anesthesia duration normalized to the human life span is much shorter
      than that shown to induce developmental abnormalities in rodents. Therefore, we
      studied whether subsequent environmental stressors contribute to deficiencies
      programmed by a brief neonatal etomidate exposure. METHODS: Postnatal days (P) 4,
      5, or 6, Sprague-Dawley rats, pretreated with vehicle or the Na+-K+-2Cl- (NKCC1)
      inhibitor, bumetanide, received two injections of etomidate resulting in
      anesthesia for 2h. To simulate stress after anesthesia, the animals were exposed
      to a single maternal separation for 3h at P10. 3-7days after exposure to
      etomidate the rats had increased hypothalamic NKCC1 mRNA and corticotropin
      releasing hormone (CRH) mRNA and decreased K+-2Cl- (KCC2) mRNA levels with
      greater changes in males. In rats neonatally exposed to both etomidate and
      maternal separation, these abnormalities persisted into adulthood. These animals
      also exhibited extended corticosterone responses to restraint stress with
      increases in total plasma corticosterone more robust in males, as well as
      behavioral abnormalities. Pretreatment with the NKCC1 inhibitor ameliorated most
      of these effects. CONCLUSIONS: Post-anesthesia stressors may exacerbate/unmask
      neurodevelopmental abnormalities even after a relatively short anesthetic with
      etomidate, leading to dysregulated stress response systems and neurobehavioral
      deficiencies in adulthood. Amelioration by bumetanide suggests a mechanistic role
      for etomidate-enhanced gamma-aminobutyric acid type A receptor-mediated
      depolarization in initiating long-lasting alterations in gene expression that are
      further potentiated by subsequent maternal separation.

PMID- 28433804
TI  - Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries
      in rats.
AB  - We aimed to evaluate the effect of natural antioxidant crocin in alleviating
      hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin
      during resuscitation. Mortality at 12h and 24h post resuscitation was documented.
      HS and resuscitation induced organ injuries, as characterized by elevated wet/dry
      ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate
      aminotransferase and alanine aminotransferase, whereas rats received crocin
      treatment demonstrated improvements in all the above characteristics. This
      protective effect coincided with reduced malondialdehyde and increased
      glutathione in both serum and lung tissues, indicating attenuated oxidative
      stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver
      were also reduced. Crocin can potentially be used to protect organs from HS
      induced damages during resuscitation due to its anti-oxidative role.

PMID- 28433805
TI  - Chronic early childhood exposure to arsenic is associated with a TNF-mediated
      proteomic signaling response.
AB  - Exposure to inorganic arsenic (iAs) in drinking water is a global public health
      concern and is associated with a range of health outcomes, including immune
      dysfunction. Children are a particularly sensitive population to the effects of
      inorganic arsenic, yet the biological mechanisms underlying adverse health
      outcomes are understudied. Here we used a proteomic approach to examine the
      effects of iAs exposure on circulating serum protein levels in a cross-sectional
      children's cohort in Mexico. To identify iAs-associated proteins, levels of total
      urinary arsenic (U-tAs) and its metabolites were determined and serum proteins
      assessed for differences in expression. The results indicate an enrichment of
      Tumor Necrosis Factor-(TNF)-regulated immune and inflammatory response proteins
      that displayed decreased expression levels in relation to increasing U-tAs.
      Notably, when analyzed in the context of the proportions of urinary arsenic
      metabolites in children, the most robust response was observed in relation to the
      monomethylated arsenicals. This study is among the first serum proteomics
      assessment in children exposed to iAs.

PMID- 28433806
TI  - Polymorphism of CYP1A1 gene variants rs4646903 and rs1048943 relation to the
      incidence of cervical cancer in Chhattisgarh.
AB  - Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in
      the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is
      therefore possible that polymorphism of CYP1A1 gene producing functional changes
      in the enzyme may be susceptible factors in cervical carcinogenesis. This study
      was aimed to look association of CYP1A1m1 (T>C) and m2 (A>G) gene polymorphisms
      in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA
      from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls). All
      subjects were genotyped for CYP1A1m1 (T>C) and m2 (A>G) using PCR-RFLP with
      statistical analysis by using SPSS version 16.0 and VassarStats (online). Among
      the two gene variants rs4646903 (T>C) and rs1048943 (A>G), individuals with AG
      and GG genotypes of CYP1A1m2 polymorphism have significantly higher and increased
      risk of cervical cancer (OR=2.0, 95%CI=1.04-3.84, p=0.035; OR=62.9, 95%CI=3.72
      1063.83, p=0.004 respectively) and the association of CYP1A1m1 polymorphism did
      not show any significant relationship with cervical cancer patients (p=0.23). The
      'G' allele showed strong association with the disease (p<0.0001). Thus, CYP1A1m2
      polymorphism showed an increased risk in the population leading to cervical
      cancer. Our study suggested that the presence of 'C' allele of rs4646903 (T>C)
      showed no risk and 'G' allele of rs1048943 (A>G) might be a leading allele to
      cause increased cervical cancer susceptibility due to significant association of
      CYP1A1m2 gene polymorphism.

PMID- 28433807
TI  - Silver nanoparticle induced toxicity to human sperm by increasing ROS(reactive
      oxygen species) production and DNA damage.
AB  - Silver nanoparticles (AgNPs) have been used in medical products and industrial
      coatings, due to their antimicrobial properties. Excessive use of AgNPs can have
      adverse effects on the human body, however, their toxicity characteristics to
      human sperm and the potential mechanisms are not entirely clear. In this study,
      we exposed human sperm to different doses of AgNPs (0, 50MUgml-1, 100MUgml-1,
      200MUgml-1 or 400MUgml-1) for various times (15min, 30min, or 60min), followed by
      analyses of the sperm viability, motility and the ratio of abnormal to normal
      sperm.Then, transmission electron microscopy(TEM) was used to explore the sperm
      ultrastructural characteristics. Reactive oxygen species production and DNA
      fragmentation were tested using standard kits and the sperm chromatin dispersion
      method, respectively. The results showed a dose- and time-dependent decline in
      sperm viability and motility and an increased ratio of abnormal to normal sperm
      after 30min and 60min of exposure to AgNPs at 200MUgml-1 and 400MUgml-1. The most
      common abnormalities were sperm heads with disrupted chromatin or absent
      acrosomes, bent tails, and curved mid-pieces. The ultrastructural characteristics
      of AgNP-treated sperm included disrupted, swollen, granular and vacuolar defects
      of the chromatin. In addition, ROS(reactive oxygen species)production and DNA
      fragmentation were markedly increased after 60min of exposure to AgNPs at
      200MUgml-1 and 400MUgml-1. Our results indicated that AgNPs caused detrimental
      changes in human sperm characteristics, and the excessive use of AgNPs should be
      carried out with caution.

PMID- 28433808
TI  - Comparisons of hip strength and countermovement jump height in elite tennis
      players with and without acute history of groin injuries.
AB  - BACKGROUND: Despite the high groin-injury (GI) prevalence in tennis, no studies
      have assessed the extent to which intrinsic groin injury risk factors, such as
      hip muscle strength, have recovered in elite tennis players with a history of
      previous GI. OBJECTIVE: To investigate whether elite tennis players with a
      history of GI show differences in hip strength and jump height between injured
      and uninjured limbs and compared with dominant limb in tennis players without
      history of acute groin-injuries (NGI). DESIGN: Cohort study. PARTICIPANTS: Sixty
      one tennis players completed this study: 17 in the GI group and 44 in the NGI.
      Isometric adductor and abductor hip strength were assessed with a handheld
      dynamometer, and unilateral counter-movement jump tests were performed on a
      contact mat connected to an Ergo tester. Paired t-tests were conducted to
      identify differences between injured and non-injured limbs in the GI group, and
      independent measures t-tests were conducted to compare between GI and NGI groups.
      RESULTS: Isometric adductor strength and adductor/abductor strength ratios were
      lower in the injured limb (16.4% and 20.1%, respectively) compared with uninjured
      side within the GI group, and lower than the dominant side in the NGI group. No
      significant differences were found for unilateral jump heights between sides in
      the GI, nor isometric abductor strength, when comparing GI to NGI groups.
      CONCLUSIONS: Isometric adductor weakness and adductor/abductor strength ratio
      deficits suggest that adductor muscle strength is not fully recovered in these
      athletes, potentially increasing their risk of a repeat groin injury.

PMID- 28433809
TI  - Biocorona formation on gold nanoparticles modulates human proximal tubule kidney
      cell uptake, cytotoxicity and gene expression.
AB  - Gold nanoparticles (AuNP) adsorb macromolecules to form a protein corona (PC)
      after systemic delivery, to which the kidney as the primary excretory organ is
      constantly exposed. The role of the PC on AuNP cell uptake and toxicity was
      investigated in vitro in human proximal tubule cells (HPTC) using 40 and 80nm
      branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG)
      coated AuNP with or without (bare) PCs composed of human plasma (HP) or human
      serum albumin (HSA) for 0.25 to 24h. Time-dependent intracellular uptake,
      assessed by ICP-MS showed PC modulated cell uptake and cytotoxicity; with bare
      40nm BPEI-AuNP showing the greatest responses. All AuNP showed minimal to no
      cytokine release. At the nontoxic dose, 40nm bare BPEI-AuNP significantly
      modified gene expression related to immunotoxicity, steatosis, and mitochondrial
      metabolism; while at the high dose, pathways of DNA damage and repair, apoptosis,
      fatty acid metabolism and heat shock response were modulated. HP corona BPEI-AuNP
      response was comparable to control. These studies clearly showed reduced uptake
      and cytotoxicity, as well as differentiated gene expression of AuNP with PCs,
      questioning the utility of in vitro studies using bare NP to assess in vivo
      effects. Significantly, only cationic bare BPEI-AuNP had HPTC uptake or
      cytotoxicity suggesting the relative safety of PEG and LA-AuNP as nanomedicine
      constructs.

PMID- 28433810
TI  - Generation mechanism of nonlinear ultrasonic Lamb waves in thin plates with
      randomly distributed micro-cracks.
AB  - Since the identification of micro-cracks in engineering materials is very
      valuable in understanding the initial and slight changes in mechanical properties
      of materials under complex working environments, numerical simulations on the
      propagation of the low frequency S0 Lamb wave in thin plates with randomly
      distributed micro-cracks were performed to study the behavior of nonlinear Lamb
      waves. The results showed that while the influence of the randomly distributed
      micro-cracks on the phase velocity of the low frequency S0 fundamental waves
      could be neglected, significant ultrasonic nonlinear effects caused by the
      randomly distributed micro-cracks was discovered, which mainly presented as a
      second harmonic generation. By using a Monte Carlo simulation method, we found
      that the acoustic nonlinear parameter increased linearly with the micro-crack
      density and the size of micro-crack zone, and it was also related to the
      excitation frequency and friction coefficient of the micro-crack surfaces. In
      addition, it was found that the nonlinear effect of waves reflected by the micro
      cracks was more noticeable than that of the transmitted waves. This study
      theoretically reveals that the low frequency S0 mode of Lamb waves can be used as
      the fundamental waves to quantitatively identify micro-cracks in thin plates.

PMID- 28433811
TI  - Rapid and sensitive detection of salmonid alphavirus using TaqMan real-time PCR.
AB  - Salmonid alphavirus (SAV) infection has led to the spread of salmon pancreas
      disease (PD) and sleeping disease (SD) to salmonids in several countries in
      Europe, resulting in tremendous economic losses to the fish farming industry.
      Recently, with increases in the fish import trade, many countries in which SAV
      has been unreported, such as China, may be seriously threatened by these
      diseases. It is therefore necessary to develop efficient detection methods for
      the prevention and diagnosis of SAV infection. In this study, a rapid and
      sensitive TaqMan real-time PCR method was established and assessed for this
      purpose. A specificity assay showed no cross-reactions with other common RNA
      viruses. Regression analysis and standard curves calculated from the Ct values of
      10-fold serial dilutions of the standard plasmid showed that the assay was highly
      reproducible over a wide range of RNA input concentrations. The real-time PCR
      assay was able to detect SAV at a concentration as low as 1.5 * 101 copies,
      indicating that it is 107 times more sensitive than the approved conventional RT
      PCR method (detection limit, 1.5 * 107 copies) after use on the same samples.
      Assessment of infected fish samples showed that this assay has a higher
      sensitivity than the previously reported Q_nsP1 assay. Thus, this TaqMan real
      time PCR assay provides a rapid, sensitive, and specific detection method for
      SAV, offering improved technical support for the clinical diagnosis and
      epidemiology of SAV.

PMID- 28433812
TI  - The perlecan-interacting growth factor progranulin regulates ubiquitination,
      sorting, and lysosomal degradation of sortilin.
AB  - Despite extensive clinical and experimental studies over the past decades, the
      pathogenesis and progression to the castration-resistant stage of prostate cancer
      remains largely unknown. Progranulin, a secreted growth factor, strongly binds
      the heparin-sulfate proteoglycan perlecan, and counteracts its biological
      activity. We established that progranulin acts as an autocrine growth factor and
      promotes prostate cancer cell motility, invasion, and anchorage-independent
      growth. Progranulin was overexpressed in prostate cancer tissues vis-a-vis non
      neoplastic tissues supporting the hypothesis that progranulin may play a key role
      in prostate cancer progression. However, progranulin's mode of action is not well
      understood and proteins regulating progranulin signaling have not been
      identified. Sortilin, a single-pass type I transmembrane protein of the Vps10
      family, binds progranulin in neurons and targets progranulin for lysosomal
      degradation. Significantly, in DU145 and PC3 cells, we detected very low levels
      of sortilin associated with high levels of progranulin production and enhanced
      motility. Restoring sortilin expression decreased progranulin levels, inhibited
      motility and anchorage-independent growth and destabilized Akt. These results
      demonstrated a critical role for sortilin in regulating progranulin and suggest
      that sortilin loss may contribute to prostate cancer progression. Here, we
      provide the novel observation that progranulin downregulated sortilin protein
      levels independent of transcription. Progranulin induced sortilin ubiquitination,
      internalization via clathrin-dependent endocytosis and sorting into early
      endosomes for lysosomal degradation. Collectively, these results constitute a
      regulatory feed-back mechanism whereby sortilin downregulation ensures sustained
      progranulin-mediated oncogenesis.

PMID- 28433813
TI  - New tools to make percutaneous epicardial access safer: Is the real-time
      pressure/frequency monitoring on the needle tip the best way?

PMID- 28433814
TI  - Synovial fluid pro-inflammatory profile differs according to the characteristics
      of knee pain.
AB  - OBJECTIVE: The role of inflammation and pain in osteoarthritis (OA) is not fully
      understood. We evaluated the association between pro-inflammatory biomarkers and
      pain. METHODS: We used baseline data and samples from a randomized controlled
      trial of colchicine for symptomatic knee OA. Severity of pain of the more
      symptomatic knee was assessed by National Health and Nutrition Examination Survey
      I (NHANES-I) criterion and Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) pain index. Pains on movement and at rest were self
      reported on an 11-point Likert scale. Severity of radiographic tibiofemoral OA
      was assessed by Kellgren and Lawrence (KL) grade. Concentrations of synovial
      fluid (sf) IL-1beta, IL-6, IL-8, TNFalpha, C-terminal telopeptides of Type I
      collagen (CTXI) and C-telopeptide of Type II collagen (CTXII), as well as urinary
      (u) CTXII were measured. RESULTS: Of the 109 patients enrolled in the study, 70
      patients (70% women) with synovial fluid obtained by direct aspiration were
      included for analysis. The mean +/- SD age and body mass index (BMI) of the
      patients were 57.6 +/- 8.3 years and 28.8 +/- 5.2 kg/m2. After adjustment for
      age, sex, and BMI, sf IL-6 and IL-8 were statistically significantly associated
      with 11-point pain on movement, but not with pain at rest. No significant
      associations were observed with WOMAC pain scores. sf IL-1beta (analyzed as
      detectable/non-detectable) was inversely associated with pain. In contrast, after
      adjustment, Sf TNFalpha was associated with WOMAC total pain and both pain on
      movement and at rest. sf/u CTXII was associated with radiographic severity, but
      not with knee pain. CONCLUSIONS: This study provides indication that OA pain
      mechanisms may differ according to the characteristics of the pain.

PMID- 28433816
TI  - L-carnitine prevents memory impairment induced by chronic REM-sleep deprivation.
AB  - Sleep deprivation (SD) negatively impacts memory, which was related to oxidative
      stress induced damage. L-carnitine is a naturally occurring compound, synthesized
      endogenously in mammalian species and known to possess antioxidant properties. In
      this study, the effect of L-carnitine on learning and memory impairment induced
      by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep
      deprivation was induced using modified multiple platform model (8h/day, for 6
      weeks). Simultaneously, L-carnitine was administered (300mg/kg/day)
      intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was
      used to assess spatial learning and memory. Additionally, the hippocampus levels
      of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized
      glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and
      superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS)
      were assessed. The results showed that chronic REM-sleep deprivation impaired
      both short- and long-term memory (P<0.05), whereas L-carnitine treatment
      protected against this effect. Furthermore, L-carnitine normalized chronic REM
      sleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG,
      activity of catalase, GPx, and SOD. No change was observed in TBARS among tested
      groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory
      impairment, and treatment with L-carnitine prevented this impairment through
      normalizing antioxidant mechanisms in the hippocampus.

PMID- 28433817
TI  - Climate change risks, extinction debt, and conservation implications for a
      threatened freshwater fish: Carmine shiner (Notropis percobromus).
AB  - Climate change is affecting many freshwater species, particularly fishes.
      Predictions of future climate change suggest large and deleterious effects on
      species with narrow dispersal abilities due to limited hydrological connectivity.
      In turn, this creates the potential for population isolation in thermally
      unsuitable habitats, leading to physiological stress, species declines or
      possible extirpation. The current extent of many freshwater fish species' spatio
      temporal distribution patterns and their sensitivity to thermal impacts from
      climate change - critical information for conservation planning - are often
      unknown. Carmine shiner (Notropis percobromus) is an ecologically important
      species listed as threatened or imperilled nationally (Canada) and regionally
      (South Dakota, United States) due to its restricted range and sensitivity to
      water quality and temperature. This research aimed to determine the current
      distribution and spatio-temporal variability in projected suitable habitat for
      Carmine shiner using niche-based modeling approaches (MaxEnt, BIOCLIM, and DOMAIN
      models). Statistically downscaled, bias-corrected Global Circulation Models
      (GCMs) data was used to model the distribution of Carmine shiner in central North
      America for the period of 2041-2060 (2050s). Maximum mean July temperature and
      temperature variability were the main factors in determining Carmine shiner
      distribution. Patterns of projected habitat change by the 2050s suggest the
      spatial extent of the current distribution of Carmine shiner would shift north,
      with >50% of the current distribution changing with future projections based on
      two Representative Concentrations Pathways for CO2 emissions. Whereas the
      southern extent of the distribution would become unsuitable for Carmine shiner,
      suitable habitats are predicted to become available further north, if accessible.
      Importantly, the majority of habitat gains for Carmine shiner would be in areas
      currently inaccessible due to dispersal limitations, suggesting current
      populations may face an extinction debt within the next half century. These
      results provide evidence that Carmine shiner may be highly vulnerable to a
      warming climate and suggest that management actions - such as assisted migration 
      may be needed to mitigate impacts from climate change and ensure the long-term
      persistence of the species.

PMID- 28433815
TI  - Patterns and predictors of persistent opioid use following hip or knee
      arthroplasty.
AB  - OBJECTIVE: The relationship between arthroplasty and long-term opioid use in
      patients with knee or hip osteoarthritis is not well studied. We examined the
      prevalence, patterns and predictors of persistent opioid use after hip or knee
      arthroplasty. METHOD: Using claims data (2004-2013) from a US commercial health
      plan, we identified adults who underwent hip or knee arthroplasty and filled >=1
      opioid prescription within 30 days after the surgery. We defined persistent
      opioid users as patients who filled >=1 opioid prescription every month during
      the 1-year postoperative period based on group-based trajectory models.
      Multivariable logistic regression was used to determine preoperative predictors
      of persistent opioid use after surgery. RESULTS: We identified 57,545 patients
      who underwent hip or knee arthroplasty. The mean +/- SD age was 61.5 +/- 7.8
      years and 87.1% had any opioid use preoperatively. Overall, 7.6% persistently
      used opioids after the surgery. Among patients who used opioids in 80% of the
      time for >=4 months preoperatively (n = 3023), 72.1% became persistent users. In
      multivariable analysis, knee arthroplasty vs hip, a longer hospitalization stay,
      discharge to a rehabilitation facility, preoperative opioid use (e.g., a longer
      duration and greater dosage and frequency), a higher comorbidity score, back
      pain, rheumatoid arthritis, fibromyalgia, migraine and smoking, and
      benzodiazepine use at baseline were strong predictors for persistent opioid use
      (C-statistic = 0.917). CONCLUSION: Over 7% of patients persistently used opioids
      in the year after hip or knee arthroplasty. Given the adverse health effects of
      persistent opioid use, strategies need to be developed to prevent persistent
      opioid use after this common surgery.

PMID- 28433818
TI  - Spatial-temporal variability and transportation mechanism of polychlorinated
      biphenyls in the Yangtze River Estuary.
AB  - Although the variability of polychlorinated biphenyls (PCBs) is strongly
      dependent on the hydro-sediment pattern, the quantification of this interaction
      is still not well described, especially for estuary areas. In this study, both
      chemical analyses and numerical simulation were conducted to explain the temporal
      spatial variability and transportation mechanism of PCBs in the Yangtze River
      Estuary (YRE). The impacts of the upstream Three Gorges Dam (TGD) on estuarine
      PCBs were also addressed with a simulated scenario. The results showed that the
      PCBs levels in the YRE were relatively low or moderate and the highest levels
      were related to the maximum turbidity zone. The spatial variability of PCBs is
      strongly dependent on the hydrological circulation, which resulted in a declining
      trend from the inner YRE to the adjacent sea. The seasonal variability of PCBs
      could be due to the joint influence of the current and the erosion/deposition
      environment. The opposite temporal trends of the overlaying water and sediment
      are driven by the seasonal characteristics of hydro-sediment patterns. The
      simulated results also indicated that the distribution, fluxes and transport
      ability of PCBs in the South Branch changed as a result of the sediment discharge
      reduction after construction of the TGD.

PMID- 28433819
TI  - Environmentally and economically efficient utilization of coal processing waste.
AB  - High concentrations of hazardous anthropogenic emissions (sulfur, nitrogen and
      carbon oxides) from solid fuel combustion in coal burning plants cause
      environmental problems that have been especially pressing over the last 20-30
      years. A promising solution to these problems is a switch from conventional
      pulverized coal combustion to coal-water slurry fuel. In this paper, we pay
      special attention to the environmental indicators characterizing the combustion
      of different coal ranks (gas, flame, coking, low-caking, and nonbaking coals) and
      coal-water slurry fuels based on the coal processing waste - filter cakes. There
      have been no consistent data so far on the acceptable intervals for the
      anthropogenic emissions of sulfur (SOx), nitrogen (NOx) and carbon (CO, CO2)
      oxides. Using a specialized combustion chamber and gas analyzing system, we have
      measured the concentrations of typical coal and filter-cake-based CWS combustion
      products. We have also calculated the typical combustion heat of the fuels under
      study and measured the ratio between environmental and energy attributes. The
      research findings show that the use of filter cakes in the form of CWS is even
      better than coals in terms of environment and economy. Wide utilization of filter
      cakes solves many environmental problems: the areas of contaminated sites shrink,
      anthropogenic emissions decrease, and there is no need to develop new coal mines
      anymore.

PMID- 28433820
TI  - Effects of punctal occlusion on global tear proteins in patients with dry eye.
AB  - PURPOSE: To investigate effects of punctal occlusion on global tear protein
      levels in patients with dry eye. METHODS: In this prospective, longitudinal,
      single-center study, nonabsorbable punctal plugs were inserted bilaterally into
      the lower punctum of 30 patients with moderate dry eye. Dry eye symptoms,
      fluorescein corneal staining, Schirmer I test, tear film break-up time, and
      safety were assessed in the more severely affected eye. Tear proteins at weeks 1
      and 3 were quantified by iTRAQ relative to baseline preocclusion levels. RESULTS:
      Of 29 patients who completed the study, 23 (mean age 49.8 years) had sufficient
      tear samples for analysis. After 3 weeks, punctal occlusion significantly
      upregulated tear proteins, including glutathione synthase (mean of 1.6-fold, P =
      0.01) and interleukin-1 receptor antagonist (1.7-fold, P = 0.032) and
      downregulated cholinergic receptor (neuronal) alpha-7 (0.79-fold, P = 0.039) and
      lymphocyte cytosolic protein-1 (0.66-fold, P = 0.012). Clustering analysis of
      global tear proteins revealed two clear profile changes; the first group of
      patients (cluster 1, n = 10) had a reduction in the inflammatory proteins (e.g.,
      S100A8) and rise in lacrimal proteins supporting the ocular surface (e.g.,
      lysozyme), whereas the second group (cluster 2, n = 13) had an increase in
      inflammatory proteins and a decrease in lacrimal proteins. Logistic regression
      analysis revealed that cluster 1 patients had significantly (P = 0.006) lower
      Schirmer scores at baseline (mean [standard deviation]: 4.3 [4.3] mm) than
      cluster 2 (6.8 [2.6] mm). CONCLUSIONS: Punctal plugs produced a beneficial
      pattern of tear protein change in patients with relatively low Schirmer scores
      within 3 weeks of punctal occlusion.

PMID- 28433821
TI  - Developmental change in children's sensitivity to sound symbolism.
AB  - The current study examined developmental change in children's sensitivity to
      sound symbolism. Three-, five-, and seven-year-old children heard sound symbolic
      novel words and foreign words meaning round and pointy and chose which of two
      pictures (one round and one pointy) best corresponded to each word they heard.
      Task performance varied as a function of both word type and age group such that
      accuracy was greater for novel words than for foreign words, and task performance
      increased with age for both word types. For novel words, children in all age
      groups reliably chose the correct corresponding picture. For foreign words, 3
      year-olds showed chance performance, whereas 5- and 7-year-olds showed reliably
      above-chance performance. Results suggest increased sensitivity to sound symbolic
      cues with development and imply that although sensitivity to sound symbolism may
      be available early and facilitate children's word-referent mappings, sensitivity
      to subtler sound symbolic cues requires greater language experience.

PMID- 28433822
TI  - Programming experience promotes higher STEM motivation among first-grade girls.
AB  - The gender gap in science, technology, engineering, and math (STEM) engagement is
      large and persistent. This gap is significantly larger in technological fields
      such as computer science and engineering than in math and science. Gender gaps
      begin early; young girls report less interest and self-efficacy in technology
      compared with boys in elementary school. In the current study (N=96), we assessed
      6-year-old children's stereotypes about STEM fields and tested an intervention to
      develop girls' STEM motivation despite these stereotypes. First-grade children
      held stereotypes that boys were better than girls at robotics and programming but
      did not hold these stereotypes about math and science. Girls with stronger
      stereotypes about robotics and programming reported lower interest and self
      efficacy in these domains. We experimentally tested whether positive experience
      with programming robots would lead to greater interest and self-efficacy among
      girls despite these stereotypes. Children were randomly assigned either to a
      treatment group that was given experience in programming a robot using a
      smartphone or to control groups (no activity or other activity). Girls given
      programming experience reported higher technology interest and self-efficacy
      compared with girls without this experience and did not exhibit a significant
      gender gap relative to boys' interest and self-efficacy. These findings show that
      children's views mirror current American cultural messages about who excels at
      computer science and engineering and show the benefit of providing young girls
      with chances to experience technological activities.

PMID- 28433823
TI  - Simultaneous monitoring of intra- and extracellular nitric oxide in living cells
      by means of dual-color fluorescence imaging.
AB  - A dual-color fluorescence imaging method for simultaneous monitoring of intra-
      and extracellular nitric oxide (NO) was developed. Assisted by confocal laser
      scanning microscope, the intra- and extracellular NO can be successfully
      visualized by using two selected probes, 4,4-difluoro-8-(3,4-diaminophenyl)-3,5
      bis(4-methoxyphenyl)-4-bora-3a,4a-diaza-s-indacene (p-MOPB) and disodium 2,6
      disulfonate-1,3-dimethyl-5-hexadecyl-8-(3,4-diaminophenyl)-4,4'-difluoro-4-bora
      3a,4a-diaza-s-indacene (DSDMHDAB), which display distinct membrane permeability
      and show different colors of fluorescence after reaction with NO. Results
      indicated that intra- and extracellular NO could be fluorometrically detected
      without mutual interference. The applicability of the proposed method was
      validated by dual-color imaging of NO on both sides of the plasma membrane in RAW
      264.7 murine macrophages and human vascular endothelial (ECV-304) cells. This
      multi-labeling approach using multi-laser excitation and multi-color fluorescence
      detection holds great promise for simultaneous analysis of NO as well as other
      gasotransmitters in living cells with subcellular resolution.

PMID- 28433824
TI  - ENFSI collaborative testing programme for fingermarks: Past experiences and
      future perspectives.
AB  - As early as 2004 the Fingerprint Working Group of the European Network of
      Forensic Science Institutes (ENFSI) has organised proficiency tests (PT's) as
      well as collaborative exercises (CE's) as a way of raising standards within the
      fingerprint profession. Participation in PT's and CE's is a key element in the
      ISO/IEC accreditation process as they enable laboratories to monitor the quality
      of their analytical results. On the basis of the European Council Framework
      Decision 2009/905/JHA, of 30 November 2009, on Accreditation of forensic service
      providers carrying out laboratory activities[1], from November 15th of 2015, only
      accredited laboratories are allowed to exchange fingerprint data with other EU
      countries. This article will provide an overview of the ENFSI collaborative tests
      for fingermarks in the fields of visualisation, imaging and individualisation.
      The characteristics of the testing programme are summarised, followed by an
      overview of the knowledge that has been gained, including lessons learnt. It is
      hoped that this reflective process can outline the critical issues that should be
      addressed as well as highlight future opportunities in relation to Monopoly
      Project 2013, "Proficiency Tests and Collaborative Exercises for the Fingerprint
      Domain".

PMID- 28433825
TI  - A distributed framework for health information exchange using smartphone
      technologies.
AB  - Nationwide health information exchange (NHIE) continues to be a persistent
      concern for government agencies, despite the many efforts and the conceived
      benefits of sharing patient data among healthcare providers. Difficulties in
      ensuring global connectivity, interoperability, and concerns on security have
      always hampered the government from successfully deploying NHIE. By looking at
      NHIE from a fresh perspective and bearing in mind the pervasiveness and power of
      modern mobile platforms, this paper proposes a new approach to NHIE that builds
      on the notion of consumer-mediated HIE, albeit without the focus on central
      health record banks. With the growing acceptance of smartphones as reliable,
      indispensable, and most personal devices, we suggest to leverage the concept of
      mobile personal health records (PHRs installed on smartphones) to the next level.
      We envision mPHRs that take the form of distributed storage units for health
      information, under the full control and direct possession of patients, who can
      have ready access to their personal data whenever needed. However, for the actual
      exchange of data with health information systems managed by healthcare providers,
      the latter have to be interoperable with patient-carried mPHRs. Computer industry
      has long ago solved a similar problem of interoperability between peripheral
      devices and operating systems. We borrow from that solution the idea of providing
      special interfaces between mPHRs and provider systems. This interface enables the
      two entities to communicate with no change to either end. The design and
      operation of the proposed approach is explained. Additional pointers on potential
      implementations are provided, and issues that pertain to any solution to
      implement NHIE are discussed.

PMID- 28433826
TI  - Data summarization method for chronic disease tracking.
AB  - OBJECTIVES: Bearing in mind the rising prevalence of chronic medical conditions,
      the chronic disease management is one of the key features required by medical
      information systems used in primary healthcare. Our research group paid a
      particular attention to this specific area by offering a set of custom data
      collection forms and reports in order to improve medical professionals' daily
      routine. The main idea was to provide an overview of history for chronic
      diseases, which, as it seems, had not been properly supported in previous
      administrative workflows. After five years of active use of medical information
      systems in more than 25 primary healthcare institutions, we were able to identify
      several scenarios that were often end-user-action dependent and could result in
      the data related to chronic diagnoses being loosely connected. An additional
      benefit would be a more effective identification of potentially new patients
      suffering from chronic diseases. METHODS: For this particular reason, we
      introduced an extension of the existing data structures and a summarizing method
      along with a specific tool that should help in connecting all the data related to
      a patient and a diagnosis. The summarization method was based on the principle of
      connecting all of the records pertaining to a specific diagnosis for the selected
      patient, and it was envisaged to work in both automatic and on-demand mode. The
      expected results were a more effective identification of new potential patients
      and a completion of the existing histories of diseases associated with chronic
      diagnoses. RESULTS: The current system usage analysis shows that a small number
      of doctors used functionalities specially designed for chronic diseases affecting
      less than 6% of the total population (around 11,500 out of more than 200,000
      patients). In initial tests, the on-demand data summarization mode was applied in
      general practice and 89 out of 155 users identified more than 3000 new patients
      with a chronic disease over a three-month test period. During the tests, more
      than 100,000 medical documents were paired up with the existing histories of
      diseases. Furthermore, a significant number of physicians that accepted the
      standard history of disease helped with the identification of the additional 22%
      of the population. Applying the automatic summarization would help identify all
      patients with at least one record related to the diagnosis usually marked as
      chronic, but ultimately, this data had to be filtered and medical professionals
      should have the final say. Depending on the data filter definition, the total
      percentage of newly discovered patients with a chronic disease is between 35% and
      53%, as expected. CONCLUSIONS: Although the medical practitioner should have the
      final say about any medical record changes, new, innovative methods which can
      help in the data summarization are welcome. In addition to being focused on the
      summarization in relation to the patient, or to the diagnosis, this proposed
      method and tool can be effectively used when the patient-diagnosis relation is
      not one-to-one but many-to-many. The proposed summarization principles were
      tested on a single type of the medical information system, but can easily be
      applied to other medical software packages, too. Depending on the existing data
      structure of the target system, as well as identified use cases, it is possible
      to extend the data and customize the proposed summarization method.

PMID- 28433827
TI  - A comparison of medication administration errors from original medication
      packaging and multi-compartment compliance aids in care homes: A prospective
      observational study.
AB  - BACKGROUND: No published study has been specifically designed to compare
      medication administration errors between original medication packaging and multi
      compartment compliance aids in care homes, using direct observation. OBJECTIVES:
      Compare the effect of original medication packaging and multi-compartment
      compliance aids on medication administration accuracy. DESIGN: Prospective
      observational. SETTING: Ten Greater London care homes. PARTICIPANTS: Nurses and
      carers administering medications. METHODS: Between October 2014 and June 2015, a
      pharmacist researcher directly observed solid, orally administered medications in
      tablet or capsule form at ten purposively sampled care homes (five only used
      original medication packaging and five used both multi-compartment compliance
      aids and original medication packaging). The medication administration error rate
      was calculated as the number of observed doses administered (or omitted) in error
      according to medication administration records, compared to the opportunities for
      error (total number of observed doses plus omitted doses). RESULTS: Over 108.4h,
      41 different staff (35 nurses, 6 carers) were observed to administer medications
      to 823 residents during 90 medication administration rounds. A total of 2452
      medication doses were observed (1385 from original medication packaging, 1067
      from multi-compartment compliance aids). One hundred and seventy eight medication
      administration errors were identified from 2493 opportunities for error (7.1%
      overall medication administration error rate). A greater medication
      administration error rate was seen for original medication packaging than multi
      compartment compliance aids (9.3% and 3.1% respectively, risk ratio (RR)=3.9, 95%
      confidence interval (CI) 2.4 to 6.1, p<0.001). Similar differences existed when
      comparing medication administration error rates between original medication
      packaging (from original medication packaging-only care homes) and multi
      compartment compliance aids (RR=2.3, 95%CI 1.1 to 4.9, p=0.03), and between
      original medication packaging and multi-compartment compliance aids within care
      homes that used a combination of both medication administration systems (RR=4.3,
      95%CI 2.7 to 6.8, p<0.001). A significant difference in error rate was not
      observed between use of a single or combination medication administration system
      (p=0.44). CONCLUSION: The significant difference in, and high overall, medication
      administration error rate between original medication packaging and multi
      compartment compliance aids supports the use of the latter in care homes, as well
      as local investigation of tablet and capsule impact on medication administration
      errors and staff training to prevent errors occurring. As a significant
      difference in error rate was not observed between use of a single or combination
      medication administration system, common practice of using both multi-compartment
      compliance aids (for most medications) and original packaging (for medications
      with stability issues) is supported.

PMID- 28433828
TI  - Poly-cyclodextrin cryogels with aligned porous structure for removal of
      polycyclic aromatic hydrocarbons (PAHs) from water.
AB  - Cyclodextrins (CDs) are sugar-based cyclic oligosaccharides, which form inclusion
      complexes with small guest molecules through their hydrophobic cavity. Here we
      successfully synthesized highly porous poly-cyclodextrin (poly-CD) cryogels,
      which were produced under cryogenic conditions by the cross-linking of amine
      functional CDs with PEG-based diepoxide cross-linker. The poly-CD cryogels showed
      aligned porous network structures owing to the directional freezing of the
      matrix, of which the pore size and architecture exposed variations depending on
      the composition of the reactants. The cryogels were employed for the removal of
      genotoxic polycyclic aromatic hydrocarbons (PAHs) from aqueous solutions. They
      reached PAH sorption capacities as high as 1.25mg PAH per gram cryogel. This high
      sorption performance is due to interactions between PAHs and the complete swollen
      network, and thus, is not restricted by interfacial adsorption. Given that the
      hydrophilic nature of the components, the sorption performance could only be
      attributed to the inclusion complex formation of CDs with PAH molecules. The poly
      CD cryogels could be recycled with an exposure to ethanol and reused without any
      significant loss in the sorption capacity of PAHs.

PMID- 28433829
TI  - Successful Repeat Sacroplasty in a Patient With a Recurrent Sacral Insufficiency
      Fracture: A Case Presentation.
AB  - : The standard of care for treatment of sacral insufficiency fracture (SIF)
      remains conservative management with limited weight-bearing and analgesics, as
      most fractures heal within 12 weeks. For those who fail to respond to
      conservative therapy, are immobile, or cannot tolerate the pain despite analgesic
      therapy, as well as those who do not improve with time, rest, or activity
      modification, minimally invasive surgery with percutaneous transverse screw
      fixation across the fracture is effective. However, a less invasive procedure,
      percutaneous sacroplasty, may be an option for potential rapid pain reduction.
      This is a novel report of repeat sacroplasty in a patient with a recurrent SIF to
      the same anatomical area as a previously treated SIF. To our knowledge, this is
      the first report of such an occurrence. LEVEL OF EVIDENCE: Not applicable.

PMID- 28433830
TI  - Spasticity Management: The Current State of Transcranial Neuromodulation.
AB  - : This narrative review aims to provide an objective view of the noninvasive
      neuromodulation (NINM) protocols available for treating spasticity, including
      repetitive transcranial magnetic stimulation (rTMS) and transcranial direct
      current stimulation (tDCS). On the basis of the relevant randomized controlled
      trials, we infer that NINM is more effective in reducing spasticity when combined
      with the conventional therapies than used as a stand-alone treatment. However,
      the magnitude of NINM after-effects depends significantly on the applied
      hemisphere and the underlying pathology. Being in line with these arguments, low
      frequency rTMS and cathodal-tDCS over the unaffected hemisphere are more
      effective in reducing spasticity than high-frequency rTMS and anodal-tDCS over
      the affected hemisphere in chronic poststroke. However, most of the studies are
      heterogeneous in the stimulation setup, patient selection, follow-up duration,
      and the availability of the sham operation. Therefore, the available data on the
      usefulness of NINM in reducing spasticity need to be confirmed by larger and
      multicentric randomized controlled trials to gather evidence on the efficiency of
      NINM regimens in reducing spasticity in various neurologic conditions. LEVEL OF
      EVIDENCE: V.

PMID- 28433831
TI  - Ultrasonography of the Transverse Movement and Deformation of the Median Nerve
      and Its Relationships With Electrophysiological Severity in the Early Stages of
      Carpal Tunnel Syndrome.
AB  - BACKGROUND: To date, there have been conflicting suggestions regarding the
      initial pathogenesis of carpal tunnel syndrome (CTS). It has been characterized
      as either inflammation of the median nerve caused by compression or
      noninflammatory fibrosis of the subsynovial connective tissue (SSCT). OBJECTIVE:
      To investigate the initial pathogenesis of CTS, we compared the deformation and
      displacement of the median nerve in accordance with the electrophysiological
      severity between patients with CTS (via the Bland scale) and healthy controls.
      DESIGN: Cross-sectional, case-control study. SETTING: General teaching hospital,
      rehabilitation unit. PATIENTS: Thirteen hands of 10 healthy participants and 39
      hands of 27 patients with CTS were recruited and classified into 4 groups (stage
      0-3) according to the severity of the electrodiagnostic test results. METHODS:
      Ultrasound images of the median nerve in response to the wrist and finger motions
      were analyzed. MAIN OUTCOME MEASURE: We measured the deformation of the median
      nerve (the maximal change values of the median nerve area, and aspect ratio of
      the minimum-enclosing rectangle [MER]) and movement of the median nerve (the
      maximal change value of the median nerve displacement) in response to the motions
      of wrists and finger. The maximal change value of the median nerve displacement
      was normalized with respect to the width of the wrist. Moreover, the maximal
      change values of the median nerve area, and the aspect ratio of the MER, were
      also normalized to the median nerve area and the aspect ratio of the MER in wrist
      neutral position with finger extension. RESULT: CTS patients in stage 3 showed a
      significantly lower normalized maximal change of the median nerve movement
      compared with CTS patients in stages 0, 1, and 2 (P <.001). Regarding the
      deformation of the median nerve, however, there were statistically significant
      differences among all groups (area, P < .001; MER, P <.001). According to
      multivariate logistic regression analysis, the normalized maximal change of the
      aspect ratio of the MER is a meaningful parameter in diagnosing the initial stage
      of CTS (P < .01). CONCLUSION: These results showed that the deformation of the
      median nerve may be associated with the initial pathogenesis; however, further
      studies are necessary to validate the findings of this study. LEVEL OF EVIDENCE:
      III.

PMID- 28433832
TI  - The theoretical study of excited-state intramolecular proton transfer of 2,5
      bis(benzoxazol-2-yl)thiophene-3,4-diol.
AB  - The symmetrical structures 2,5-bis(benzoxazol-2-yl)thiophene-3,4-diol (BBTD) can
      take shape two intramolecular hydrogen bonds in chloroform. In order to research
      the molecular dynamic behavior of BBTD upon photo-induced process, we utilize
      density functional theory (DFT) and time-dependent density functional theory
      (TDDFT) to complete theoretical calculation. Through the comparison of bond
      length, bond angle, IR spectra, and frontier molecular orbitals between ground
      state (S0) and first excited state (S1), it clearly indicates that
      photoexcitation have slightly influence for intensity of hydrogen bond. For the
      sake of understanding the mechanism of excited state intramolecular proton
      transfer (ESIPT) of BBTD in chloroform, potential energy surfaces have been
      scanned along with the orientation of O1-H2 and O4-H5 in S0 and S1 state,
      respectively. A intrigued hydrogen bond dynamic phenomenon has been found that
      ESIPT of BBTD is not a synergetic double proton transfer process, but a stepwise
      single proton transfer process BBTD->BBTD-S->BBTD-D. Moreover, the proton
      transfer process of BBTD-S->BBTD-D is easier to occur than that of BBTD->BBTD-S
      in S1 state.

PMID- 28433833
TI  - In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and
      BSA of some gold(III) complexes with N,N'-ethylenediamine bidentate ester
      ligands.
AB  - Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R2eddl}]PF6
      (R2eddl=O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R=n
      Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by
      elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution
      mass spectrometry. Density functional theory calculations pointed out that (R,R)
      N,N'-configuration diastereoisomers were energetically the most favorable. Duo to
      high cytotoxic activity complex 3 was chosen for stability study in DMSO, no
      decomposition occurs within 24h, and for the reaction with ascorbic acid in which
      was reduced immediately. Additionally, 3 interacts with bovine serum albumin
      (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was
      determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia
      (K562), and human melanoma (Fem-x) cancer cell lines, as well as against non
      cancerous human embryonic lung fibroblast cells MRC-5. The highest activity was
      observed against K562 cells (IC50: 5.04-6.51MUM). Selectivity indices showed that
      these complexes are less toxic than cisplatin. 3 had a similar viability kinetics
      on HeLa cells as cisplatin. Drug accumulation studies in HeLa cells showed that
      the total gold uptake increased much faster than that of cisplatin pointing out
      that 3 more efficiently enters the cells than cisplatin. Furthermore,
      morphological and cell cycle analysis reveal that gold(III) complexes induced
      apoptosis in time- and dose-dependent manner.

PMID- 28433834
TI  - Antimicrobial and anticancer photodynamic activity of a phthalocyanine
      photosensitizer with N-methyl morpholiniumethoxy substituents in non-peripheral
      positions.
AB  - Photodynamic therapy involves the use of a photosensitizer that is irradiated
      with visible light in the presence of oxygen, resulting in the formation of
      reactive oxygen species. A novel phthalocyanine derivative, the quaternary iodide
      salt of magnesium(II) phthalocyanine with N-methyl morpholiniumethoxy
      substituents, was synthesized, and characterized. The techniques used included
      mass spectrometry (MALDI TOF), UV-vis, NMR spectroscopy, and photocytotoxicity
      against bacteria, fungi and cancer cells. The phthalocyanine derivative possessed
      typical characteristics of compounds of the phthalocyanine family but the effect
      of quaternization was observed on the optical properties, especially in terms of
      absorption efficiency. The results of the photodynamic antimicrobial effect study
      demonstrated that cationic phthalocyanine possesses excellent photodynamic
      activity against planktonic cells of both Gram-positive and Gram-negative
      bacteria. The bactericidal effect was dose-dependent and all bacterial strains
      tested were killed to a significant degree by irradiated phthalocyanine at a
      concentration of 1*10-4M. There were no significant differences in the
      susceptibility of Gram-positive and Gram-negative bacteria to the applied
      photosensitizer. The photosensitivity of bacteria in the biofilm was lower than
      that in planktonic form. No correlation was found between the degree of biofilm
      formation and susceptibility to antimicrobial photodynamic inactivation. The
      anticancer activity of the novel phthalocyanine derivative was tested using A549
      adenocarcinomic alveolar basal epithelial cells and the human oral squamous cell
      carcinoma cells derived from tongue (HSC3) or buccal mucosa (H413). No
      significant decrease in cell viability was observed under different conditions or
      with different formulations of the compound.

PMID- 28433835
TI  - The relationship between pre-verbal event representations and semantic
      structures: The case of goal and source paths.
AB  - We explored the nature of infants' concepts for goal path and source path in
      motion events (e.g., the duck moved into the bowl/out of the bowl), specifically
      asking how infants' representations could support the acquisition of the semantic
      roles of goal path and source path in language. The results showed that 14.5
      month-old infants categorized goal paths across different motion events (moving
      to X, moving on Y), and they also categorized source paths if the source
      reference objects were highly salient (relatively large in size and colorful).
      Infants at 10months also categorized goal paths, suggesting that the broad
      concept GOAL PATH precedes the acquisition of the relevant spatial terms (e.g.,
      "to", "onto"). These results are discussed in terms of the nature of goal and
      source path representations in infancy (e.g., whether they are represented at a
      general level - one that encompasses specific relations such as containment and
      support) as well as the possible mechanisms that may be involved in the mapping
      of these representations to language.

PMID- 28433836
TI  - Recent advances in diagnostic and therapeutic guidelines for primary and
      secondary hemophagocytic lymphohistiocytosis.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory
      syndrome characterized by excessive activation of macrophages and T cells
      resulting from defective cytotoxicity. It is potentially life threatening due to
      the large amounts of cytokines released by the activated macrophages and
      lymphocytes secondary to a hyperinflammatory response. It has a high fatality in
      children with an incidence of approximately 1.2cases/million per year. METHOD:
      The literature was extensively searched in PubMed, MEDLINE and Google scholar.
      RESULTS: A variable and nonspecific symptomatology can delay the diagnosis and
      hence requires a high index of suspicion in both primary and secondary HLH.

PMID- 28433837
TI  - Internal Maxillary Bypass for Complex Pediatric Aneurysms.
AB  - BACKGROUND: Complex pediatric aneurysms (PAs) are an unusual clinicopathologic
      entity. Data regarding the use of a bypass procedure to treat complex PAs are
      limited. METHODS: Internal maxillary artery-to-middle cerebral artery bypass with
      radial artery graft was used to isolate PAs. Bypass patency and aneurysm
      stability were evaluated using intraoperative Doppler ultrasound, indocyanine
      green videoangiography, and postoperative angiography. Modified Rankin Scale was
      used to assess neurologic function. RESULTS: Over a 5-year period, 7 pediatric
      patients (<=18 years old) were included in our analysis. Mean age of patients was
      14.4 years (range, 12-18 years), and mean size of PAs was 23.6 mm (range, 9-37
      mm). All cases manifested with complex characteristics. Proximal artery occlusion
      was performed in 3 cases, complete excision following aneurysmal distal internal
      maxillary artery bypass was performed in 2 cases, and combined proximal artery
      occlusion and aneurysm excision was performed in the 2 remaining cases. Mean
      intraoperative blood flow was 61.6 mL/minute (range, 40.0-90.8 mL/minute). Graft
      patency rate was 100% during postoperative recovery and at the last follow-up
      examination (mean, 20 months; range, 7-45 months). All patients had excellent
      outcomes except for 1 patient who died of multiple-organ failure. CONCLUSIONS:
      Internal maxillary artery bypass is an essential technique for treatment of
      selected cases of complex PAs.

PMID- 28433838
TI  - Outcome of Anterior Lumbar Interbody Fusion: A Retrospective Study of Clinical
      and Radiologic Parameters.
AB  - OBJECTIVE: This study critically evaluates the long-term results of standalone
      anterior lumbar interbody fusion (ALIF), without use of rhBMP-2, as a therapeutic
      option for symptomatic patients with degenerative disc disease (DDD).
      Furthermore, this study intends to identify predictive parameters for anterior
      lumbar interbody fusion outcome. METHODS: A retrospective cohort study with
      additional telephone interview to obtain missing data was performed. All patients
      who underwent an L4-L5 or L5-S1 ALIF-procedure, or both, in the period between
      2006 and 2011 were identified. The medical files of 123 patients with 154 fusion
      levels were reviewed. All patients were contacted by telephone to gather
      supplementary and missing information. Pain and functionality scores (Visual
      Analogue Scale [VAS] and Oswestry Disability Index [ODI]), radiologic
      (intervertebral disc height, Modic and Pfirrmann classifications), and different
      clinical parameters were gathered. RESULTS: The mean age of the population at
      surgery was 46.2 years. Overall, 59 female and 64 male patients were included in
      the study. The mean VAS score for back and leg pain improved significantly (P <
      0.001) with 5 and 4.4 points respectively at 3-year follow-up. Modic-type I
      changes are associated with a better improvement in VAS score for back pain (P =
      0.026), Pfirrmann-grades IV and V and an intervertebral disc height of less than
      5 mm are associated with a better improvement in leg pain (respective P-values:
      0.045 and 0.033). Overall, 89% of patients would reconsider the surgical
      intervention. CONCLUSIONS: The ALIF technique is a durable treatment option for
      patients with DDD. This study suggests different predictive parameters for
      treatment outcome.

PMID- 28433839
TI  - The Diagnostic Accuracy of Evoked Potential Monitoring Techniques During
      Intracranial Aneurysm Surgery for Predicting Postoperative Ischemic Damage: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To investigate the diagnostic accuracy of various evoked potential
      monitoring techniques in predicting postoperative neurologic deficit in
      intracranial aneurysm surgery. METHODS: A literature search of the MEDLINE,
      Embase, and Cochrane databases was conducted for English language articles
      published between March 31, 1983 and March 31, 2016. Original studies that
      reported the use of evoked potential monitoring during intracranial aneurysm
      surgery in predicting postoperative neurologic damage were selected, and their
      relevant reference lists were hand searched. Test performance characteristics
      were summarized using hierarchic summary receiver operating characteristic (ROC)
      curves and bivariable random-effects models. RESULTS: Thirteen qualifying studies
      (1597 patients; 1689 aneurysms) from 6 countries were identified. Eight studies
      investigated the use of the somatosensory evoked potential (SSEP) monitoring
      technique, 5 investigated transcranial motor evoked potential (TcMEP) and another
      5 investigated direct cortical motor evoked potential (DMEP). Bivariable pooled
      sensitivity and specificity were 48% (95% confidence interval [CI], 30.7-65.0)
      and 92% (CI, 88%-94.4%), respectively, for SSEP; 73% (CI, 21.0%-96.7%) and 94%
      (CI, 87.1%-97.5%) for TcMEP; and 97% (CI, 74.43%-99.99%) and 89% (CI, 84.0%
      94.5%) for DMEP. ROC curve analysis showed that TcMEP had the highest accuracy
      (area under ROC curve 0.95; 95% CI, 0.93-0.97), followed by DMEP (0.91, 0.89
      0.94) and SSEP (0.88, 0.85-0.91). CONCLUSIONS: TcMEP and DMEP have higher
      diagnostic accuracy than SSEP in predicting postoperative neurologic deficit. The
      type of anesthetic agent, the use of neuromuscular blocking drugs, and the choice
      of diagnostic criteria for significant change in cerebral blood flow during
      aneurysm surgery affect the diagnostic accuracy of evoked potential techniques in
      predicting postoperative neurologic deficit.

PMID- 28433840
TI  - The Unusual Presentation of a Myxoma Within the Sphenoid Sinus: Case Report and
      Review of the Literature.
AB  - BACKGROUND: We describe a rare case of a sphenoid sinus myxoma that was resected
      via an endoscopic endonasal skull base approach. We review the literature
      regarding these rare tumors of the paranasal sinuses. CASE DESCRIPTION: A 72-year
      old woman was diagnosed with an incidental sphenoid sinus tumor and left sphenoid
      wing meningioma during a workup for left-sided proptosis and diplopia. Biopsies
      of the sphenoid wing and sphenoid sinus tumors were obtained. After undergoing
      surgical resection of the meningioma, the patient then underwent definitive
      resection of the sphenoid sinus myxoma via endoscopic endonasal skull base
      approach. Postoperative imaging demonstrated a gross total resection. The patient
      suffered postoperative thromboembolic complications due to underlying
      hypercoagulable state but made a complete recovery and returned to her neurologic
      baseline. There has been no evidence of recurrent myxoma in the sphenoid sinus 24
      months after surgery. DISCUSSION: Myxomas are benign tumors derived from
      primitive mesenchyme. Myxomas very rarely present in the paranasal or skull base
      location. Complete surgical resection is the primary treatment for these tumors.
      The endoscopic endonasal approach is an effective technique for resecting various
      benign and more aggressive extradural skull base tumors. CONCLUSIONS: Myxomas of
      the sphenoid sinus are rare. The endoscopic endonasal skull base approach is an
      effective and minimal access technique for resection of this rare tumor of the
      sphenoid sinus.

PMID- 28433842
TI  - Therapeutic Options for Recurrent High-Grade Gliomas: A Perspective Statement.

PMID- 28433841
TI  - A Simple and Reliable Method for the Diagnosis of Ventriculoperitoneal Shunt
      Malfunction.
AB  - OBJECTIVE: To provide a simple and reliable method for the diagnosis of
      ventriculoperitoneal shunt malfunction. METHODS: A total of 14 participants were
      enrolled in this study, consisting of 7 patients with suspected shunt malfunction
      and 7 control cases with apparent normal drainage. In all cases, 0.1 mL of 5%
      glucose solution was injected into the reservoir and 0.1 mL of cerebrospinal
      fluid was withdrawn from the reservoir 20 minutes later to measure glucose
      concentration. RESULTS: The glucose concentration in cerebrospinal fluid of the
      shunt malfunction group was greater than that of the control group (P < 0.05).
      CONCLUSIONS: The proposed method is reliable, safe, and relatively simple for the
      diagnosis of ventriculoperitoneal shunt malfunction and provides a reference for
      treatment.

PMID- 28433843
TI  - Use of Pneumoperitoneal Puncture for Peritoneal Catheter Placement in
      Lumboperitoneal Shunt Surgery: Technical Note.
AB  - BACKGROUND: In hydrocephalus shunt surgery, a peritoneal catheter is
      traditionally inserted with laparotomy incision. The abdominal incision length
      will not be shorter than 3 cm in most cases. A longer incision has to be made in
      obese patients. The lateral position in lumboperitoneal shunt (LPS) surgery also
      increases the difficulty of laparotomy. This report introduces a simple technique
      of pneumoperitoneal puncture for peritoneal catheter placement in LPS surgery.
      METHODS: Twenty-eight communicating hydrocephalus cases underwent
      pneumoperitoneal puncture in an LPS operation. Abdominal incision length, time
      for peritoneal catheter placement, and postoperative complications were recorded.
      RESULTS: The length of the abdominal incision was 1 cm, and the average time for
      peritoneal catheter placement was 3.5 minutes. No patient suffered from infection
      and obstruction. Two cases of subdural hematoma because of cerebrospinal fluid
      overdrainage occurred. CONCLUSIONS: The pneumoperitoneal puncture technique has
      proven, in our experience, to be a minimally invasive, simple, and reliable
      method in a peritoneal catheter placement procedure. This technique, which needs
      to be assessed further by larger case series, may be considered a new method of
      choice for peritoneal catheter placement in LPS surgery.

PMID- 28433844
TI  - Neurologic Decline in an Older Patient with Repaired Myelomeningocele Complicated
      with Lumbar Canal Stenosis.
AB  - BACKGROUND: Tethered cord syndrome is a well-known complication after
      myelomeningocele (MMC) repair in childhood. However, late complications in adults
      with a repaired MMC are not well understood. In particular, the influence of a
      degenerative spinal deformity on a sustained tethered cord is still unclear. CASE
      DESCRIPTION: A 63-year-old man with a repaired MMC exhibited a progressive gait
      disturbance and numbness in both lower limbs. Magnetic resonance imaging
      demonstrated that the tethered spinal cord was compressed by severe canal
      stenosis along the entire lumbar spine. After a multi-level lumbar decompression
      surgery, the patient recovered to baseline neurologic status. CONCLUSION: In
      adults with a repaired MMC, lumbar canal stenosis should be investigated as a
      possible cause of late neurologic decline. Clinical manifestations may be
      complicated by the coexistence of both the original and subsequent neurologic
      disorders. Because these additional disorders result from compressive myelopathy,
      early surgical decompression is indicated to avoid irreversible spinal cord
      dysfunction.

PMID- 28433845
TI  - Clinical Outcome After Extended Endoscopic Endonasal Resection of
      Craniopharyngiomas: Two-Institution Experience.
AB  - BACKGROUND: The extended endoscopic endonasal approach (EEA) to the anterior
      cranial base is used for the resection of craniopharyngiomas. OBJECTIVE: We
      present clinical experience and outcomes of using EEA for craniopharyngiomas.
      METHODS: A total of 116 patients in 2 remote institutions were enrolled in this
      retrospective study. Surgical, endocrinologic, and ophthalmologic outcomes were
      assessed. RESULTS: The mean follow-up was 35 months (range, 1-115). Gross total
      resection (GTR), near total resection (NTR, >95%), and subtotal resection (STR)
      were achieved in 46%, 39%, and 15% of the patients, respectively. Surgery
      performed after 2010 was the only variable significantly associated with greater
      extent of resection, which might be explained by the learning curve. Overall
      tumor recurrence rate was 15.5%, with a median interval until recurrence of 14.5
      months (range, 3-58). Extent of resection was significantly associated with
      recurrence-free survival (P = 0.0116). Those who underwent NTR/STR followed by
      adjuvant radiotherapy had a similar median recurrence-free survival rate compared
      with those who underwent GTR (26.5 vs. 20 months, P = 0.167). Endocrinologic
      examination revealed that 47.4% of patients experienced worsening of anterior
      pituitary function following surgery while 25.5% developed new-onset diabetes
      insipidus. Of the 89 patients with preoperative visual deficits, 68 (76.4%)
      experienced improvement in visual field assessment. CONCLUSION: EEA is effective
      for the surgical resection of craniopharyngiomas, resulting in high rates of
      visual improvement and low complication rates. Adjuvant radiotherapy is a useful
      method for tumor control after incomplete resection.

PMID- 28433846
TI  - Factors Associated with Postoperative Complications in Hydrocephalic Infants
      Diagnosed at Bernard Mevs Hospital in Port-au-Prince, Haiti, from 2011 to 2013.
AB  - OBJECTIVE: Complications worsen the prognosis of hydrocephalic children who
      undergo surgery. The main objective of this study was to determine factors
      associated with postoperative complications in Haitian infants with hydrocephaly.
      METHODS: This was a cross-sectional study conducted on hydrocephalic infants
      diagnosed in a Haitian hospital from 2011 to 2013. Records were consulted to
      gather key variables that were evaluated in relation to the occurrence of
      postoperative complications. Any variable whose P value was less than 0.05 for
      the Mantel-Haenszel chi2 test was considered a factor associated with
      postoperative complications. RESULTS: The prevalence of hydrocephalus in our
      sample was 6.6%. Of the 131 cases of hydrocephalus surveyed, 75 were selected.
      The sex ratio was 1.02, and the age group from 1 to 6 months old was the most
      affected (52% of cases). The increase in head circumference (96% of cases) was
      the most common clinical sign. A total of 70.7% of the infants underwent imaging
      work-up, and 26.7% had central nervous system malformations. A total of 84%
      received surgical treatment, and one third of the operated infants presented with
      complications, the most common being infection (8%). Postoperative mortality was
      6.7%, and 40% of operated infants had no postoperative care after medical
      discharge. Ventriculoperitoneal shunt was more significantly associated with
      complications than endoscopic third ventriculostomy (odds ratio 3.25, P = 0.03).
      CONCLUSIONS: Hydrocephalus in Haitian infants is diagnosed late and inadequately
      investigated, treated, and monitored. Ventriculoperitoneal shunts are
      significantly related to more postoperative complications than endoscopic third
      ventriculostomy.

PMID- 28433847
TI  - Is It Reliable to Predict the Outcome of Elderly Patients with Severe Traumatic
      Brain Injury Using the IMPACT Prognostic Calculator?
AB  - BACKGROUND: Many investigators endeavor to predict the outcome based on admission
      characteristics using some established models to determine which management
      should be applied. However, the efficacy and applicability of the models using in
      the geriatric patients with severe traumatic brain injury (TBI) have not yet been
      evaluated. METHODS: A total of 137 geriatric severe TBI patients were enrolled in
      this retrospective study. Receiver operating characteristic (ROC) curves were
      constructed to evaluate the efficacy and usability of the International Mission
      for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic model in
      evaluating the prognosis for these patients. RESULTS: The observed mortality and
      unfavorable outcomes at 6 months in patients with severe TBI were 54.7% and
      70.8%, respectively, slightly lower than the predicted outcomes using the IMPACT
      model. ROC curve analysis showed areas under the curve (AUCs) for mortality of
      0.76 and for unfavorable outcome of 0.80 in the Core model, of 0.76 and 0.79,
      respectively, in the Extended model, and of 0.73 and 0.77, respectively, in the
      Lab model. When expected risk of fatal outcome was >90% in any model, the true
      positive rate was 100%. Moreover, when the predicted risk for unfavorable
      outcomes was >70% in any model, the actual rate of unfavorable outcomes was >80%.
      CONCLUSIONS: The IMPACT prognosis calculator showed just fair discrimination when
      predicting the outcome of the elderly patients with severe TBI. Management
      decisions should be made on a case-by-case basis rather than by relying on the
      predicted risks identified by this model; conservative treatment might be
      preferable when expected risk of fatal outcome is >90%.

PMID- 28433848
TI  - Instrumented Circumferential Fusion in Two Stages for Instable Lumbar Fracture:
      Long-Term Results of a Series of 74 Patients on Sagittal Balance and Functional
      Outcomes.
AB  - OBJECTIVE: To report the radiologic and functional results of a multicenter,
      prospective case series of patients with comminuted lumbar fractures treated with
      2-stage circumferential arthrodesis. METHODS: A multicenter prospective case
      series of 74 patients with comminuted lumbar fractures was analyzed. The strategy
      entailed initial posterior osteosynthesis, followed by physical replacement with
      an expandable titanium cage filled with autologous bone via retroperitoneal
      lumbotomy. The mechanism of lesion formation and epidemiologic characteristics
      were recorded. Clinical and quality-of-life analyses (visual analog scale [VAS],
      Oswesty Disability Index [ODI], Short Form 12 [SF-12]) were performed over a
      minimum observation period of 1 year. Radiologic parameters, including deformity
      measurements, were recorded at each evaluation. Fusion was analyzed by means of a
      1-year monitoring scan. RESULTS: The mean patient age was 38.1 years, and median
      duration of follow-up was 2.1 years (interquartile range, 1.3-2.9). The
      distribution of fractures according to the Magerl classification scheme was as
      follows: A, 64.8%; B, 16.7%; C, 18.5%. At the last follow-up, fusion was
      considered certain in 57 cases (77%). The mean VAS score was 2.1 +/- 1.3, mean
      ODI was 14.7 +/- 8.0, mean SF-12 Physical Component Summary score was 43.2 +/-
      9.3, and mean SF-12 Mental Component Summary score was 50.8 +/- 5.9. Correction
      of the regional sagittal deformity was significant during the postoperative
      period, with a mean increase in lordosis of 9.0 degrees  (P < 0.0001). The loss
      of mean correction at the last follow-up (-2.9 degrees ) was not significant.
      CONCLUSIONS: Circumferential arthrodesis, including posterior osteosynthesis and
      physical replacement with an expandable cage and autologous graft, is applicable
      to the treatment of comminuted lumbar fractures. A high rate of fusion was
      obtained with significant and long-lasting correction of the sagittal deformity.
      Functional scores measured at 1 year suggest mild disability. The ODI, SF-12, and
      VAS scores were positively correlated with fusion at the last follow-up.

PMID- 28433849
TI  - Clinical Significance of Long-Term Follow-Up of Children with Posttraumatic Skull
      Base Fracture.
AB  - OBJECTIVE: To assess the incidence of cerebrospinal fluid (CSF) leak and
      meningitis, and the need for prophylactic antibiotics, antipneumococcal
      vaccination, and surgical interventions, in children with a skull base fracture.
      METHODS: We reviewed the records of children with a skull base fracture who were
      admitted to our tertiary care center between 2009 and 2014. RESULTS: A total of
      196 children (153 males), age 1 month to 18 years (mean age, 6 +/- 4 years), were
      hospitalized with skull base fracture. Causes of injury were falls (n = 143),
      motor vehicle accidents (n = 34), and other (n = 19). Fracture locations were the
      middle skull base in 112 patients, frontal base in 62, and occipital base in 13.
      Fifty-four children (28%) had a CSF leak. In 34 of these children (63%),
      spontaneous resolution occurred within 3 days. Three children underwent surgery
      on admission owing to a CSF leak from an open wound, 3 underwent CSF diversion by
      spinal drainage, and 4 (2%) required surgery to repair a dural tear after failure
      of continuous spinal drainage and acetazolamide treatment. Twenty-eight children
      (14%) received prophylactic antibiotic therapy, usually due to other injuries,
      and 11 received pneumococcal vaccination. Two children developed meningitis, and
      3 children died. Long-term follow up in 124 children revealed 12 children with
      delayed hearing loss and 3 with delayed facial paralysis. CONCLUSIONS: This is
      the largest pediatric series of skull base fractures reporting rates of morbidity
      and long-term outcomes published to date. The rate of meningitis following skull
      base fracture in children is low, supporting a policy of not administering
      prophylactic antibiotics or pneumococcal vaccine. Long-term follow up is
      important to identify delayed complications.

PMID- 28433850
TI  - Surgical Resection and Histopathological Analysis of a Thrombosed Giant Fusiform
      MCA Aneurysm After Initial Treatment with a Flow Diversion Construct.
AB  - BACKGROUND: We describe the histopathology of an unruptured giant calcified left
      middle cerebral artery (MCA) fusiform aneurysm initially treated with
      endovascular flow diversion. The flow diversion construct underwent postoperative
      in-stent thrombosis, necessitating surgical resection of the aneurysm to
      eliminate mass effect. METHODS: A 75-year-old woman with a known left MCA
      aneurysm presented to the emergency department with moderate right hemibody
      weakness. Owing to the clinical and radiographic progression of the aneurysm, the
      patient was offered treatment. She was initially offered open surgical management
      of the lesion but declined it, indicating that she would consider only
      endovascular treatment. The patient underwent endovascular reconstruction of the
      aneurysmal segment with an overlapping pipeline construct. Postoperatively, the
      patient experienced in-stent thrombosis of the pipeline construct. The thrombosed
      aneurysm exerted a progressive local mass effect, necessitating en bloc surgical
      resection of the aneurysm and stent construct. The aneurysm was submitted for
      pathological analysis, which demonstrated chronologically older thrombus outside
      the flow diversion construct. RESULTS: Postsurgical imaging demonstrated a left
      MCA territory stroke. The patient gradually gained strength in her right
      hemibody. The histopathological analysis indicated that the degrees of platelet
      activation and clot formation in this case were dependent on the aggregate
      surface area of the thrombus and surface area of the pipeline device used in the
      reconstruction. CONCLUSIONS: This technical report with histopathological
      analysis provides useful insight into the mechanism of aneurysmal thrombosis
      after flow diversion. It also raises new questions regarding the roles of
      thrombus formation, platelet aggregation, and stent construct surface area in the
      maintenance of vessel patency.

PMID- 28433851
TI  - DNA Methylation Regulates Gene Expression in Intracranial Aneurysms.
AB  - BACKGROUND: Different gene expression profiles are observed in intracranial
      aneurysm tissues. Understanding these genes and what regulates their expression
      will provide insight into the pathogenesis of intracranial aneurysms. We
      investigated whether differences in DNA methylation regulate gene expression in
      intracranial aneurysms. METHODS: We compared 20 intracranial aneurysm tissue
      specimens with 20 matched specimens from the superficial temporal artery as
      controls. We identified the gene expression profiles in these samples using the
      GeneChip Human U133 Plus 2.0 array and evaluated DNA methylation modifications
      using the Infinium HumanMethylation450 BeadChip Kit. RESULTS: A total of 11,022
      differentially methylated sites between aneurysm tissues and matched control
      tissues were identified, and 2142 differentially expressed gene transcripts were
      detected based on the 2 gene expression profiles. Gene Ontology and Kyoto
      Encyclopedia of Genes and Genomes analyses and verification analysis showed that
      the MYH11, LIFR, and TLR4 genes were associated with the occurrence and
      development of intracranial aneurysms. These genes mainly encode cell adhesion
      molecules or are involved in the NF-kappaB, JAK-STAT, and ERK/JNK signaling
      pathways. CONCLUSIONS: In the development of intracranial aneurysms, DNA
      methylation plays an important role in the regulation of genetic expression
      involved in immune and inflammatory reactions, cell function, cell maintenance,
      and cell signal transduction.

PMID- 28433852
TI  - Efficiency of low versus high airline pressure in stunning cattle with a
      pneumatically powered penetrating captive bolt gun.
AB  - The efficiency of stunning cattle was assessed in 443 animals (304 pure Zebu and
      139 crossbred cattle), being mainly mature bulls and cows. Cattle were stunned
      using a Jarvis pneumatically powered penetrating captive bolt gun operating with
      low (160-175psi, N=82) and high (190psi, N=363) airline pressure, which was
      within the manufactures specifications. Signs of brain function and the position
      of the shots on the heads were recorded after stunning. Velocity of the captive
      bolt and its physical parameters were calculated. Cattle shot with low pressures
      showed more rhythmic respiration (27 vs. 8%, P<0.001), less tongue protrusion (4
      vs. 12%, P=0.03) and less masseter relaxation (22 vs. 48%, P<0.001). There was an
      increased frequency of shots in the ideal position when cattle were shot with the
      low compared to high airline pressures (15.3 vs. 3.1%). Bolt velocity and its
      physical parameters were significantly (P<0.01) higher when using high pressure.
      Airline pressures below 190psi are inappropriate when shooting adult Zebu beef
      cattle with pneumatically powered penetrating captive bolt guns.

PMID- 28433853
TI  - Addition of an extract of lucerne (Medicago sativa L.) to cattle diets - Effects
      on fatty acid profile, meat quality and eating quality of the M. longissimus
      muscle.
AB  - There is considerable interest in enhancing beneficial fatty acids, particularly
      18:3n-3, conjugated linoleic acid and long chain n-3 fatty acids such as
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in beef to provide
      benefits to human health. Here, the potential to enhance these fatty acids by
      feeding a n-3 polyunsaturated fatty acid (PUFA)-rich plant extract (PX) from
      lucerne is presented. Cattle (n=8/diet) were assigned to the following finishing
      diets: straw and concentrate (S-CC); straw and concentrate containing 25% PX and
      2000IUvitaminE/kg PX-concentrate (S-PXC); grass silage (GS); GS plus 75gPX/kg dry
      matter intake (DMI) (GS-LPX) or GS plus 150g PX/kg DMI (GS-HPX). Addition of PX
      to concentrates or GS increased the n-3 fatty acid content of loin muscle and had
      favourable effects on the n-6:n-3 PUFA ratio (P<0.05), without detrimental
      effects on loin muscle sensory characteristics.

PMID- 28433854
TI  - Comorbidity, age of onset and suicidality in obsessive-compulsive disorder (OCD):
      An international collaboration.
AB  - OBJECTIVES: To collate data from multiple obsessive-compulsive disorder (OCD)
      treatment centers across seven countries and five continents, and to report
      findings in relation to OCD comorbidity, age of onset of OCD and comorbid
      disorders, and suicidality, in a large clinical and ethnically diverse sample,
      with the aim of investigating cultural variation and the utility of the
      psychiatric diagnostic classification of obsessive-compulsive and related
      disorders. METHODS: Researchers in the field of OCD were invited to contribute
      summary statistics on current and lifetime psychiatric comorbidity, age of onset
      of OCD and comorbid disorders and suicidality in their patients with OCD.
      RESULTS: Data from 3711 adult patients with primary OCD came from Brazil (n=955),
      India (n=802), Italy (n=750), South Africa (n=565), Japan (n=322), Australia
      (n=219), and Spain (n=98). The most common current comorbid disorders were major
      depressive disorder (28.4%; n=1055), obsessive-compulsive personality disorder
      (24.5%, n=478), generalized anxiety disorder (19.3%, n=716), specific phobia
      (19.2%, n=714) and social phobia (18.5%, n=686). Major depression was also the
      most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n=1874). OCD
      generally had an age of onset in late adolescence (mean=17.9years, SD=1.9).
      Social phobia, specific phobia and body dysmorphic disorder also had an early age
      of onset. Co-occurring major depressive disorder, generalized anxiety disorder
      and psychotic disorders tended to have a later age of onset than OCD. Suicidal
      ideation within the last month was reported by 6.4% (n=200) of patients with OCD
      and 9.0% (n=314) reported a lifetime history of suicide attempt. CONCLUSIONS: In
      this large cross-continental study, comorbidity in OCD was common. The high rates
      of comorbid major depression and anxiety disorders emphasize the need for
      clinicians to assess and monitor for these disorders. Earlier ages of onset of
      OCD, specific phobia and social phobia may indicate some relatedness between
      these disorders, but this requires further study. Although there do not appear to
      be significant cultural variations in rates or patterns of comorbidity and
      suicidality, further research using similar recruitment strategies and
      controlling for demographic and clinical variables may help to determine whether
      any sociocultural factors protect against suicidal ideation or psychiatric
      comorbidity in patients with OCD.

PMID- 28433855
TI  - The electrophysiology of neuroHIV: A systematic review of EEG and MEG studies in
      people with HIV infection since the advent of highly-active antiretroviral
      therapy.
AB  - OBJECTIVE: The Human Immunodeficiency Virus (HIV) has an impact on the brain,
      even when the infection is well-controlled with modern highly-active
      antiretroviral therapy (HAART). While dementia is rare in those on HAART, milder
      cognitive impairment is common. The causes, patterns, and evolution of brain
      dysfunction in people living with HIV remain uncertain. We evaluate whether
      electrophysiological methods provide informative measures of brain dysfunction in
      this population. METHODS: A systematic literature search identified studies that
      used EEG or MEG to evaluate persons living with HIV published between 1996 (when
      HAART became available) and 2016. RESULTS: Twenty-eight studies were identified.
      Most involved small samples, and all but four were cross-sectional. Reduced
      amplitude of Event Related Potentials and decreased power in the alpha band at
      rest were the most frequent differences between people with and without HIV
      infection. Of the 16 studies that also assessed cognitive ability, 13 found a
      significant relationship between cognition and electrophysiological changes in
      the HIV+ groups. Five of those studies also reported a significant relationship
      with current immunosuppression, suggesting a direct effect of HIV on the brain.
      There were few longitudinal studies; whether these electrophysiological changes
      progress over time, or respond to treatment, remains unclear. CONCLUSIONS: EEG
      and MEG can provide useful information about brain dysfunction in people with HIV
      infection, but more consistent assessments of both cognition and EEG patterns, as
      well as longitudinal studies with larger, better characterized samples are
      needed. SIGNIFICANCE: This is the first systematic review of electrophysiological
      findings in HIV since the availability of HAART. EEG and MEG measures are
      sensitive to brain dysfunction in this population, and could complement other
      approaches in improving the assessment, understanding and treatment of
      neurocognitive disorders in HIV.

PMID- 28433856
TI  - Detection of recurrent activation patterns across focal seizures: Application to
      seizure onset zone identification.
AB  - OBJECTIVE: We introduce a method that quantifies the consistent involvement of
      intracranially monitored regions in recurrent focal seizures. METHODS: We
      evaluated the consistency of two ictal spectral activation patterns (mean power
      change and power change onset time) in intracranial recordings across focal
      seizures from seven patients with clinically marked seizure onset zone (SOZ). We
      examined SOZ discrimination using both patterns in different frequency bands and
      periods of interest. RESULTS: Activation patterns were proved to be consistent
      across more than 80% of recurrent ictal epochs. In all patients, whole-seizure
      mean activations were significantly higher for SOZ than non-SOZ regions (P<0.05)
      while activation onset times were significantly lower for SOZ than for non-SOZ
      regions (P<0.001) in six patients. Alpha-beta bands (8-20Hz) achieved the highest
      patient-average effect size on the whole-seizure period while gamma band (20
      70Hz) achieved the highest discrimination values between SOZ and non-SOZ sites
      near seizure onset (0-5s). CONCLUSIONS: Consistent spectral activation patterns
      in focal epilepsies discriminate the SOZ with high effect sizes upon appropriate
      selection of frequency bands and activation periods. SIGNIFICANCE: The present
      method may be used to improve epileptogenic identification as well as pinpoint
      additional regions that are functionally altered during ictal events.

PMID- 28433857
TI  - The relationship between joint attention and theory of mind in neurotypical
      adults.
AB  - Joint attention (JA) is hypothesized to have a close relationship with developing
      theory of mind (ToM) capabilities. We tested the co-occurrence of ToM and JA in
      social interactions between adults with no reported history of psychiatric
      illness or neurodevelopmental disorders. Participants engaged in an experimental
      task that encouraged nonverbal communication, including JA, and also ToM
      activity. We adapted an in-lab variant of experience sampling methods (Bryant et
      al., 2013) to measure ToM during JA based on participants' subjective reports of
      their thoughts while performing the task. This experiment successfully elicited
      instances of JA in 17/20 dyads. We compared participants' thought contents during
      episodes of JA and non-JA. Our results suggest that, in adults, JA and ToM may
      occur independently.

PMID- 28433858
TI  - Reduced graphene oxide-chitosan-aptamer interface as new platform for
      ultrasensitive detection of human epidermal growth factor receptor 2.
AB  - The present work describes an ultrasensitive electrochemical aptamer-based assay
      for detection of human epidermal growth factor receptor 2 protein (HER2) cancer
      biomarker as a model analyte. Results show that the reduced graphene oxide
      chitosan (rGO-Chit) film as a suitable electrode material possesses great
      favorable properties including high homogeneity, good stability, large surface
      area and high fraction of amine groups as aptamer binding sites. Various steps of
      aptasensor fabrication were characterized using microscopic, energy-dispersive X
      ray spectroscopy (EDAX), Fourier transform infrared (FTIR) spectroscopy and
      electrochemical techniques. Using methylene blue (MB) as an electrochemical probe
      and differential pulse voltammetry (DPV) technique, two linear concentration
      ranges of 0.5-2ngml-1 and 2-75ngml-1 were obtained with a high sensitivity of
      0.14MUAng-1ml and a very low detection limit of 0.21ngml-1 (very lower than the
      clinical cut-off). The fabricated aptasensor showed excellent selectivity for
      detection of HER2 in complex matrix of human serum samples. The sensitive
      detection of HER2 can be attributed to the multiple signal amplification of MB
      during its accumulation to the modified electrode surface via both affinity
      interaction to aptamer molecules and electrostatic adsorption to the HER2 analyte
      as well as high charge transfer kinetic properties of the applied rGO-Chit film.
      The rapid and simple preparation of the proposed aptasensor as well as its high
      selectivity, stability and reproducibility provided a promising protocol for non
      invasive diagnosis for various points of care application. The proposed
      aptasensor showed excellent analytical performance in comparison with current
      HER2 biosensors.

PMID- 28433859
TI  - Photoelectrochemical immunosensor for methylated RNA detection based on g
      C3N4/CdS quantum dots heterojunction and Phos-tag-biotin.
AB  - N6-methyladenosine (m6A) is an enigmatic and abundant internal modification in
      eukaryotic messenger RNA (mRNA), which could affect various aspects of RNA
      metabolism and mRNA translation. Herein, a novel photoelectrochemical (PEC)
      immunosensor was constructed for m6A detection based on the inhibition of Cu2+ to
      the photoactivity of g-C3N4/CdS quantum dots (g-C3N4/CdS) heterojunction, where g
      C3N4/CdS heterojunction was used as photoactive material, anti-m6A antibody as
      recognition unit for m6A-containing RNA, Phos-tag-biotin as link unit and avidin
      functionalized CuO as PEC signal indicator. When CuO was captured on electrode
      through biotin-avidin affinity reaction and then treated with HCl, Cu2+ could be
      released and CuxS would be formed based on the selective interaction between CdS
      and Cu2+, leading the photocurrent obviously decreased. Under the optimal
      detection conditions, the PEC biosensor displayed a linear range of 0.01-10nM and
      a low detection limit of 3.53 pM for methylated RNA determination. Furthermore,
      the developed method could also be used to detect the expression level of m6A
      methylated RNA in serum samples of breast cancer patient before and after
      operative treatment. The proposed assay strategy has a great potential for
      detecting the expression methylation level of RNA in real sample.

PMID- 28433860
TI  - Cognitive intrusion of pain and catastrophic thinking independently explain
      interference of pain in the activities of daily living.
AB  - Patients with musculoskeletal illness often report that pain interferes with
      their ability to engage in activities of daily living. Catastrophic thinking is
      consistently depicted as an important cognitive factor that hinders adjustment to
      pain. Current research has also shown that pain negatively impacts an
      individual's ability to maintain attention on the task at hand. While a measure
      of the experience of cognitive intrusion of pain (ECIP) has been recently
      developed to quantify the extent of that impact, little research has explored
      this issue in everyday settings. This study tested the mediating roles of
      cognitive intrusion of pain and pain catastrophizing scale (PCS) on the
      association of pain intensity with pain interference in 142 patients with upper
      extremity musculoskeletal illness. We found that both cognitive intrusion of pain
      (b = 0.136, bootstrap SE = 0.048, 95% BCa CI [0.052, 0.245]) and pain
      catastrophizing (b = 0.114, bootstrap SE = 0.044, 95% BCa CI [0.047, 0.221])
      partly and independently mediated the relationship between pain intensity and
      pain interference. Although comparable, the mediation effect of cognitive
      intrusion of pain was slightly larger than that of pain catastrophizing (25.7%,
      bootstrap SE = 0.094 vs. 21.5%, bootstrap SE = 0.080). Results suggest that pain
      sensations can interfere with activities of daily living through two distinct
      mechanisms. A combination of traditional cognitive behavioral therapy and
      mindfulness skills training targeting both pain catastrophizing and cognitive
      intrusion has the potential to decrease pain interference and help patients
      return to normal healthy living in spite of acute or persistent pain.

PMID- 28433861
TI  - C reactive protein and enzymatically modified LDL cooperatively promote dendritic
      cell-mediated T cell activation.
AB  - BACKGROUND: Enzymatically modified low density lipoprotein (eLDL), C reactive
      protein (CRP), dendritic cells (DCs), and T cells were shown to be involved in
      the pathogenesis of atherosclerosis. This study aimed to investigate whether eLDL
      and CRP could cooperatively promote DC-mediated T cell activation and
      proliferation. METHOD: Low density lipoprotein was isolated from healthy human
      plasma and treated with proteases and cholesterol esterase. CD14+ monocytes were
      isolated from human peripheral blood by gradient centrifugation and enriched with
      CD14 Microbeads, which were then induced with recombinant human IL-4 and
      granulocyte-macrophage colony-stimulating factor before treated with eLDL and/or
      CRP. DC differentiation was assessed by flow cytometry. T cell activation was
      induced by coculture of peripheral blood mononuclear cells with autologous DCs. T
      cell proliferation was monitored by Carboxyfluorescein succinimidyl ester weak
      and CD3 positive. Cytokine production was analyzed by enzyme-linked immunosorbent
      assay and gene expression by quantitative polymerase chain reaction. RESULTS: CRP
      and eLDL promoted monocytic DC differentiation individually and cooperatively
      evidenced by the increase of CD11b, CD13, CD40, CD80 and CD86 positive cells.
      Accordingly, the production of IL-12 and TNF-alpha was significantly increased by
      CRP and/or eLDL treatment. CRP and eLDL-treated DCs elicited strong Th1 reaction
      and T cell proliferation. CONCLUSIONS: CRP and eLDL additively promoted DC
      maturation/activation and DC-mediated T cell activation and Th1 responses.

PMID- 28433862
TI  - Left ventricular outflow tract rupture during transcatheter aortic valve
      implantation: anatomic evidence of the vulnerable area.

PMID- 28433863
TI  - Corrigendum to "Structural elucidation of a polysaccharide from Lonicera japonica
      flowers, and its neuroprotective effect on cerebral ischemia-reperfusion injury
      in rat" [Int. J. Biol. Macromol. 99 (2017) February (28) 350-357].

PMID- 28433864
TI  - Arsenic metabolism and cancer risk: A meta-analysis.
AB  - OBJECTIVE: To describe the studies that have reported association measures
      between risk of cancer and the percentage distribution of urinary inorganic
      arsenic (iAs) metabolites by anatomical site, in non-ecological epidemiological
      studies. METHODS: Studies were identified in the PubMed database in the period
      from 1990 to 2015. Inclusion criteria were: non-ecological epidemiological study,
      with histologically confirmed cancer cases, reporting the percentage distribution
      of inorganic arsenic (iAs), monomethylated (MMA) and dimethylated (DMA)
      metabolites, as well as association measures with confidence intervals (CI)
      between cancer and %iAs and/or %MMA and/or %DMA. A descriptive meta-analysis was
      performed by the method of the inverse of the variance for the fixed effects
      model and the DerSimonian and Laird's method for the random effects model.
      Heterogeneity was tested using the Q statistic and stratifying for
      epidemiological design and total As in urine. The possibility of publication bias
      was assessed through Begg's test. RESULTS: A total of 13 eligible studies were
      found, most of them were performed in Taiwan and focused on skin and bladder
      cancer. The positive association between %MMA and various types of cancer was
      consistent, in contrast to the negative relationship between %DMA and cancer that
      was inconsistent. The summary risk of bladder (OR=1.79; 95% CI: 1.42, 2.26, n=4
      studies) and lung (OR=2.44; 95% CI: 1.57, 3.80, n=2 studies) cancer increased
      significantly with increasing %MMA, without statistical heterogeneity. In
      contrast, lung cancer risk was inversely related to %DMA (OR=0.58; 95% CI: 0.36,
      0.93, n=2 studies), also without significant heterogeneity. These results were
      similar after stratifying by epidemiological design and total As in urine. No
      evidence of publication bias was found. CONCLUSION: These findings provide
      additional support that methylation needs to be taken into account when assessing
      the potential iAs carcinogenicity risk.

PMID- 28433865
TI  - High sensitivity HPLC method for analysis of in vivo extracellular GABA using
      optimized fluorescence parameters for o-phthalaldehyde (OPA)/sulfite derivatives.
AB  - Reversed-phase HPLC with derivatization using o-phthalaldehyde (OPA) and sulfite
      allows electrochemical detection of gamma-aminobutyric acid (GABA) in
      microdialysis samples. However, OPA/sulfite derivatives have been reported to
      produce lower fluorescent yield than OPA derivatives using organic thiols as the
      nucleophile. To overcome this limitation we examined excitation and emission
      spectra, reaction time, pH, and concentration of reagents in the derivatization
      solution. Optimal detection parameters were determined as lambdaex=220nm and
      lambdaem=385nm for maximal fluorescence. The derivatization reaction occurred
      immediately and the product was stable up to 24 h [corrected]. A pH of 10.4 for
      the borate buffer used in the derivatization solution was significantly better
      than lower pH. Increasing the amount of sulfite combined with diluting the
      derivatization solution in borate buffer resulted in complete separation of the
      GABA peak from contaminants without any loss in signal. Controlling the
      temperature of the detector at 15 degrees C significantly improved sensitivity
      with a detection limit of approximately 1nM. To validate this assay, we performed
      microdialysis in the dorsal striatum and ventral tegmental area (VTA) of adult
      Long Evans rats. GABA concentrations in dialysates were determined using external
      standards and standard additions, in order to further confirm interfering peaks
      were not present in biological samples. Within the dorsal striatum (n=4), basal
      GABA concentrations were 12.9+/-2.2 and 14.5+/-2.2nM (external and additions,
      respectively). Respective basal GABA concentrations in the VTA (n=3) were 4.6+/
      1.1 and 5.1+/-0.6nM. Thus, we have developed a novel, sensitive fluorescence
      method to determine GABA in microdialysates using HPLC of an OPA/sulfite
      derivative.

PMID- 28433866
TI  - The effect of vacuum assisted socket suspension on prospective, community-based
      falls by users of lower limb prostheses.
AB  - Individuals with lower limb amputation are at increased risk of falling compared
      to age-matched peers. The purpose of this study was to quantify the effect of
      socket suspension on the risk of falling, by comparing prospectively tracked
      falls between a group of participants that used vacuum assisted socket suspension
      (VASS) and a group that did not use this system. Fifteen current users of VASS
      and 12 non-VASS users received an email every two weeks for one year, with a link
      to an online survey that asked whether they fell (i.e., "unintentionally came to
      rest on a lower surface") or stumbled (i.e., lost balance but did not fall) in
      the prior two weeks. A Chi-squared test was used to compare fall and stumble risk
      between groups, after stratifying by level of amputation, and the phi coefficient
      (phi) was used to quantify effect size. While the use of VASS did not affect the
      rate of falling (i.e., falls per person year) for either persons with transtibial
      amputation (TTA) or those with transfemoral amputation (TFA), the absolute risk
      of having multiple falls was reduced by nearly 75% in the former (phi=0.83),
      which is particularly important given that recurrent falls are associated with
      more severe injuries. There was no effect of VASS on the risk of falls in TFA.
      Further work is warranted to demonstrate the persistence of these effects in
      larger, more controlled samples.

PMID- 28433868
TI  - Effects of attentional focus on walking stability in elderly.
AB  - INTRODUCTION: Balance performance in the elderly is related to psychological
      factors such as attentional focus. We investigated the effects of internal vs.
      external focus of attention and fall history on walking stability in healthy
      older adults. METHOD: Walking stability of twenty-eight healthy older adults was
      assessed by applying random unilateral decelerations on a split-belt treadmill
      and analysing the resulting balance recovery movements. The internal focus
      instruction was: concentrate on the movement of your legs, whereas the external
      focus instruction was: concentrate on the movement of the treadmill. In both
      conditions participants were asked to look ahead at a screen. Outcome measures
      were coefficient of variation of step length and step width, and characteristics
      of the centre of mass velocity time-series as analysed using statistical
      parametric mapping. Fall history was assessed using a questionnaire. RESULTS:
      After each perturbation participants required two to three strides to regain a
      normal gait pattern, as determined by the centre of mass velocity response. No
      effects were found of internal and external focus of attention instructions and
      fall history on any of the outcome measures. DISCUSSION: We conclude that,
      compared to an internal focus of attention instruction, external focus to the
      walking surface does not lead to improved balance recovery responses to gait
      perturbations in the elderly.

PMID- 28433867
TI  - Validity and repeatability of inertial measurement units for measuring gait
      parameters.
AB  - Inertial measurement units (IMUs) are small wearable sensors that have tremendous
      potential to be applied to clinical gait analysis. They allow objective
      evaluation of gait and movement disorders outside the clinic and research
      laboratory, and permit evaluation on large numbers of steps. However,
      repeatability and validity data of these systems are sparse for gait metrics. The
      purpose of this study was to determine the validity and between-day repeatability
      of spatiotemporal metrics (gait speed, stance percent, swing percent, gait cycle
      time, stride length, cadence, and step duration) as measured with the APDM Opal
      IMUs and Mobility Lab system. We collected data on 39 healthy subjects. Subjects
      were tested over two days while walking on a standard treadmill, split-belt
      treadmill, or overground, with IMUs placed in two locations: both feet and both
      ankles. The spatiotemporal measurements taken with the IMU system were validated
      against data from an instrumented treadmill, or using standard clinical
      procedures. Repeatability and minimally detectable change (MDC) of the system was
      calculated between days. IMUs displayed high to moderate validity when measuring
      most of the gait metrics tested. Additionally, these measurements appear to be
      repeatable when used on the treadmill and overground. The foot configuration of
      the IMUs appeared to better measure gait parameters; however, both the foot and
      ankle configurations demonstrated good repeatability. In conclusion, the IMU
      system in this study appears to be both accurate and repeatable for measuring
      spatiotemporal gait parameters in healthy young adults.

PMID- 28433869
TI  - Community based barriers to the wider acceptance of Solid State NMR.
AB  - During August 2015, the author surveyed 76 solid state NMR scientists from
      materials science to biology, academic to industrial, based in North America,
      Europe, India, China, Japan and Australia. The subject concerned barriers to the
      wider acceptance of solid state NMR and included the various barriers based on
      experimental, funding, vendor based and community aspects. This survey was
      confidential. However, many of the survey participants requested that at least
      the results of the part of the survey relevant to our community be made public.
      This was agreed by the commissioner of the survey and these findings were
      presented at the 'Developments and Applications of Solid State NMR', Varna,
      Bulgaria during May 2016. Following the resultant discussion, members of the
      conference requested that the author publish these findings. These findings are a
      collection of the opinions of the survey participants and include additional
      anecdotes from the author, with the intention of stimulating a community debate
      to ensure that a subject we all have close to our hearts; solid state NMR
      continues to thrive moving forwards.

PMID- 28433870
TI  - Automated detection of premature delivery using empirical mode and wavelet packet
      decomposition techniques with uterine electromyogram signals.
AB  - An accurate detection of preterm labor and the risk of preterm delivery before 37
      weeks of gestational age is crucial to increase the chance of survival rate for
      both mother and the infant. Thus, the uterine contractions measured using uterine
      electromyogram (EMG) or electro hysterogram (EHG) need to have high sensitivity
      in the detection of true preterm labor signs. However, visual observation and
      manual interpretation of EHG signals at the time of emergency situation may lead
      to errors. Therefore, the employment of computer-based approaches can assist in
      fast and accurate detection during the emergency situation. This work proposes a
      novel algorithm using empirical mode decomposition (EMD) combined with wavelet
      packet decomposition (WPD), for automated prediction of pregnant women going to
      have premature delivery by using uterine EMG signals. The EMD is performed up to
      11 levels on the normal and preterm EHG signals to obtain the different intrinsic
      mode functions (IMFs). These IMFs are further subjected to 6 levels of WPD and
      from the obtained coefficients, eight different features are extracted. From
      these extracted features, only the significant features are selected using
      particle swarm optimization (PSO) method and selected features are ranked by
      Bhattacharyya technique. All the ranked features are fed to support vector
      machine (SVM) classifier for automated differentiation and achieved an accuracy
      of 96.25%, sensitivity of 95.08%, and specificity of 97.33% using only ten EHG
      signal features. Our proposed algorithm can be used in gynecology departments of
      hospitals to predict the preterm or normal delivery of pregnant women.

PMID- 28433871
TI  - Automatic cumulative sums contour detection of FBP-reconstructed multi-object
      nuclear medicine images.
AB  - The problem of determining the contours of objects in nuclear medicine images has
      been studied extensively in the past, however most of the analysis has focused on
      a single object as opposed to multiple objects. The aim of this work is to
      develop an automated method for determining the contour of multiple objects in
      positron emission tomography (PET) and single photon emission computed tomography
      (SPECT) filtered backprojection (FBP) reconstructed images. These contours can be
      used for computing body edges for attenuation correction in PET and SPECT, as
      well as for eliminating streak artifacts outside the objects, which could be
      useful in compressive sensing reconstruction. Contour detection has been
      accomplished by applying a modified cumulative sums (CUSUM) scheme in the
      sinogram. Our approach automatically detects all objects in the image, without
      requiring a priori knowledge of the number of distinct objects in the
      reconstructed image. This method has been tested in simulated phantoms, such as
      an image-quality (IQ) phantom and two digital multi-object phantoms, as well as a
      real NEMA phantom and a clinical thoracic study. For this purpose, a GE Discovery
      PET scanner was employed. The detected contours achieved root mean square
      accuracy of 1.14 pixels, 1.69 pixels and 3.28 pixels and a Hausdorff distance of
      3.13, 3.12 and 4.50 pixels, for the simulated image-quality phantom PET study,
      the real NEMA phantom and the clinical thoracic study, respectively. These
      results correspond to a significant improvement over recent results obtained in
      similar studies. Furthermore, we obtained an optimal sub-pattern assignment
      (OSPA) localization error of 0.94 and 1.48, for the two-objects and three-objects
      simulated phantoms, respectively. Our method performs efficiently for sets of
      convex objects and hence it provides a robust tool for automatic contour
      determination with precise results.

PMID- 28433872
TI  - Biosynthesis of silver nanoparticles by using Camellia japonica leaf extract for
      the electrocatalytic reduction of nitrobenzene and photocatalytic degradation of
      Eosin-Y.
AB  - In the present study, sphere-like silver nanoparticles (Ag-NPs) were synthesized
      by using Camellia japonica leaf extract and its remediation industrial pollutants
      such as nitrobenzene and Eosin-Y (EY). As-prepared sphere-like Ag-NPs were
      characterized by various analytical and spectroscopic methods such as UV-visible
      spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy
      (FT-IR), High-resolution transmission electron microscopy (HR-TEM), Energy
      dispersive X-ray spectra (EDX), and the chemical constituents of the leaf extract
      were also analyzed by using Gas chromatography and Mass Spectroscopy (GC-MS).
      Fascinatingly, the as-prepared sphere-like Ag-NPs exhibits excellent
      electrocatalytic and photocatalytic activity for the reduction of nitrobenzene
      and photo-degradation of EY dye respectively. The Cyclic voltammetry (CV) and
      amperometric (i-t) studies realized that the electrochemical behavior of sphere
      like Ag-NPs modified electrode on nitrobenzene reduction. The proposed
      nitrobenzene sensor exhibited appreciable wide linear response range and low
      detection limit of 0.05-21MUM, 23-2593MUM and 12nM, respectively. The Ag-NPs
      modified electrode showed excellent selectivity towards the nitrobenzene
      detection even in the presence of common metal ions and nitroaromatic containing
      substances. On the other hand, Ag-NPs have excellent photocatalytic activity with
      >97% degradation of EY dye after irradiated 60min. These results indicated that
      the growth of sphere-like Ag-NPs should be a proficient.

PMID- 28433874
TI  - Systematically characterize the absorbed effective substances of Wutou Decoction
      and their metabolic pathways in rat plasma using UHPLC-Q-TOF-MS combined with a
      target network pharmacological analysis.
AB  - Wu-tou Decoction (WTD) is a famous traditional Chinese medicine (TCM) formula
      which is applied to treat arthritis and pain of joints. In this study, a
      sensitive and rapid method was developed for the separation and identification of
      the absorbed constituents and metabolites of WTD in the rats plasma by ultra high
      performance liquid chromatography coupled with quadrupole time-of-flight mass
      spectrometry (UHPLC-Q-TOF-MS). A total of 22 absorbed prototype constituents and
      49 metabolites were identified or tentatively characterized in dosed plasma. The
      possible metabolic pathways of these constituents involved sulfation,
      glucuronidation, demethylation, hydroxylation and so on. What's more, we
      optimized the conventional process ways of network pharmacology and proposed a
      new concept called target-network pharmacology (T-NP). T-NP method used the
      absorbed constituents and the corresponding target proteins to generate compound
      target network, and compare to the conventional method indifferent using the
      compounds collected from herbs, it could reduce the false positive results. We
      found that the following proteins were related to the WTD therapeutic effects,
      such as PTGS2, PTGS1, MAPK3, PPARG, TNF, IL4 and IL6. On the whole, the proposed
      method clearly presented the metabolic processes of WTD and the results gave a
      comprehensive metabolic profile of WTD in vivo for the first time. The combining
      use of the T-NP method could discover potential drug targets and disclose the
      biological processes of WTD, which will open up a new approach in the study of
      TCM in future.

PMID- 28433873
TI  - pH Dependent synthesis of two isomeric dinuclear Cerium(II) complexes:
      Structures, DNA interactions, cytotoxic activity and apoptotic study.
AB  - Two isomeric dinuclear Cerium(II) complexes 1 and 2, formulated as
      Ce2(phen)2(NO3)2(L)4 [L=phenylacetic acid, phen=1,10-phenanthroline] was
      synthesized under solvothermal conditions at different pH values. The two
      complexes were characterized by elemental analysis, IR and single crystal X-ray
      diffraction. Complexes 1 and 2 were studied the binding with DNA and against
      cytotoxic activity. Fluorescence analysis indicated that the two complexes can
      bind to DNA. The changes with different gradient concentration of DNA added into
      the complexes in absorption spectra show a strongpi-stacking interaction between
      the complexes and DNA base pairs. The Cerium(II) complexes showed good cytotoxic
      activity against cancer cell lines, being 2 the most potent complex. Apoptotic
      studies of the two novel dinuclear complexes showed significant inhibitory rate
      on cancer cell growth line KB.

PMID- 28433875
TI  - Framing causal questions about the past: The Cambrian explosion as case study.
AB  - About 540 million years ago, a rapid radiation of animal phyla radically changed
      the Earth's biota in a geological eye-blink. What caused this "Cambrian
      explosion"? Over the years, paleontologists have pointed to a wide array of
      different physical mechanisms as the causal "trigger" for the explosion. More
      recently, some paleontologists have proposed complex causal pathways to which
      multiple physical mechanisms are said to have contributed. Despite their variety,
      these answers share an assumption that a single explanation can in principle be
      constructed that identifies some factor or confluence of factors as the cause of
      the Cambrian explosion. That assumption is unjustifiable. The Cambrian explosion
      had multiple causes, and different aspects of the event are best explained by
      different causes. These different causes cannot, even in principle, be integrated
      into a single causal explanation. We can learn much about the causes of the
      Cambrian explosion-or for that matter about any historical event-but only by
      attending more carefully to how we frame our causal questions about the past.

PMID- 28433876
TI  - Maternal responsivity to infants in the "High Chair" assessment: Longitudinal
      relations with toddler outcomes in a diverse, low-income sample.
AB  - Infant-parent interactions occur across many situations, yet most home-based
      assessments of parenting behaviors are conducted under conditions of low stress,
      such as free play. In this study, low-income mothers from the Early Head Start
      Research and Evaluation Project were observed at home interacting with their 14
      month-olds in the mildly stressful "High Chair" assessment (n=1718 dyads). This
      methodological study tested whether High Chair maternal responsiveness and
      detachment predicted later toddler cognitive and emotion outcomes, over and above
      equivalent maternal predictors during free play. High Chair responsiveness and
      detachment were significant, although modest, predictors of child cognitive and
      emotion outcomes, over and above maternal responsiveness and detachment during
      free play; except High Chair responsiveness did not predict the emotion outcome.
      There were no significant differences between ethnic groups in prediction of
      outcomes. Results are discussed in terms of the methodological value of assessing
      parenting behaviors across diverse situations and populations.

PMID- 28433877
TI  - Affordances in the home environment for motor development: Validity and
      reliability for the use in daycare setting.
AB  - The range of stimuli provided by physical space, toys and care practices
      contributes to the motor, cognitive and social development of children. However,
      assessing the quality of child education environments is a challenge, and can be
      considered a health promotion initiative. This study investigated the validity of
      the criterion, content, construct and reliability of the Affordances in the Home
      Environment for Motor Development - Infant Scale (AHEMD-IS), version 3-18 months,
      for the use in daycare settings. Content validation was conducted with the
      participation of seven motor development and health care experts; and, face
      validity by 20 specialists in health and education. The results indicate the
      suitability of the adapted AHEMD-IS, evidencing its validity for the daycare
      setting a potential tool to assess the opportunities that the collective context
      offers to child development.

PMID- 28433878
TI  - Effect of freshwater sediment characteristics on the persistence of fecal
      indicator bacteria and genetic markers within a Southern California watershed.
AB  - In this study, the aging of culturable FIB and DNA representing genetic markers
      for Enterococcus spp. (ENT1A), general Bacteroides (GB3), and human-associated
      Bacteroides (HF183) in freshwater sediments was evaluated. Freshwater sediment
      was collected from four different sites within the upper and lower reach of the
      Topanga Creek Watershed and two additional comparator sites within the Santa
      Monica Bay, for a total of six sites. Untreated (ambient) and oven-dried (reduced
      microbiota) sediment was inoculated with 5% sewage and artificial freshwater.
      Microcosms were held for a 21-day period and sampled on day 0, 1, 3, 5, 7, 12,
      and 21. There were substantial differences in decay among the sediments tested,
      and decay rates were related to sediment characteristics. In the ambient
      sediments, smaller particle size and higher levels of organic matter and
      nutrients (nitrogen and phosphorus) were associated with increased persistence of
      the GB3 marker and culturable Escherichia coli (cEC) and enterococci (cENT). The
      HF183 marker exhibited decay rates of -0.50 to -0.96 day-1, which was 2-5 times
      faster in certain ambient sediments than decay of culturable FIB and the ENT1A
      and GB3 markers. The ENT1A and GB3 markers decayed at rates of between -0.07 and 
      0.28 and -0.10 to -0.44 day-1, and cEC and cENT decayed at rates of between -0.22
      and -0.81 and -0.03 and -0.40 day-1, respectively. In the oven-dried sediments,
      increased persistence of all indicators and potential for limited growth of
      culturable FIB and the GB3 and ENT1A markers was observed. A simplified two-box
      model using the HF183 marker and cENT decay rates generated from the microcosm
      experiments was applied to two reaches within the Topanga Canyon watershed in
      order to provide context for the variability in decay rates observed. The model
      predicted lower ambient concentrations of enterococci in sediment in the upper
      (90 MPN g-1) versus lower Topanga watershed (530 MPN g-1) and low ambient levels
      of the HF183 marker (below the LLOQ) in sediments in both lower and upper
      watersheds. It is important to consider the variability in the persistence of
      genetic markers and FIB when evaluating indicators of fecal contamination in
      sediments, even within one watershed.

PMID- 28433879
TI  - Sulfamethoxazole degradation in anaerobic sulfate-reducing bacteria sludge
      system.
AB  - Sulfamethoxazole (SMX) is one of the most commonly used antibiotics. SMX
      degradation in sulfate-reducing bacteria (SRB) sludge systems has not been
      reported so far. This research investigated the SMX degradation using SRB sludge
      in a sulfate-reducing up-flow sludge bed reactor. Moreover, the mechanisms and
      kinetics of SMX removal were also investigated using SRB sludge via a series of
      batch experiments. The results showed that SMX removal was characterized by a
      rapid sorption onto SRB sludge, and desorption from SRB sludge to aqueous phase
      until achieving equilibrium, and then followed by slow biodegradation.
      Biodegradation was the dominant route for SMX removal. The sorption process
      conformed well to a pseudo-second-order kinetic model, meaning that the sorption
      occurred primarily via a chemical sorption process. The removal of SMX followed
      the pseudo-zero-order kinetic model with a specific removal rate of 13.2 +/- 0.1
      MUg/L/d at initial SMX concentration 100 MUg/L in batch tests. Based on the
      analysis of metabolites, most of the SMX biotransformation products' structures
      altered in the isoxazole ring, which were significantly different from that
      produced by aerobic and anaerobic sludge systems. Thus, SRB sludge system could
      play an important role in SMX biodegradation, especially in Sulfate-reduction
      Autotrophic denitrification and Nitrification Integrated (SANI) process for
      sewage treatment.

PMID- 28433880
TI  - Predicting trace organic compound attenuation by ozone oxidation: Development of
      indicator and surrogate models.
AB  - Ozone oxidation has been demonstrated to be an effective treatment process for
      the attenuation of trace organic compounds (TOrCs); however, predicting TOrC
      attenuation by ozone processes is challenging in wastewaters. Since ozone is
      rapidly consumed, determining the exposure times of ozone and hydroxyl radical
      proves to be difficult. As direct potable reuse schemes continue to gain
      traction, there is an increasing need for the development of real-time monitoring
      strategies for TOrC abatement in ozone oxidation processes. Hence, this study is
      primarily aimed at developing indicator and surrogate models for the prediction
      of TOrC attenuation by ozone oxidation. To this end, the second-order kinetic
      equations with a second-phase Rct value (ratio of hydroxyl radical exposure to
      molecular ozone exposure) were used to calculate comparative kinetics of TOrC
      attenuation and the reduction of indicator and spectroscopic surrogate
      parameters, including UV absorbance at 254 nm (UVA254) and total fluorescence
      (TF). The developed indicator model using meprobamate as an indicator compound
      and the surrogate models with UVA254 and TF exhibited good predictive power for
      the attenuation of 13 kinetically distinct TOrCs in five filtered and unfiltered
      wastewater effluents (R2 values > 0.8). This study is intended to help provide a
      guideline for the implementation of indicator/surrogate models for real-time
      monitoring of TOrC abatement with ozone processes and integrate them into a
      regulatory framework in water reuse.

PMID- 28433881
TI  - Fouling behavior of lysozyme on different membrane surfaces during the MD
      operation: An especial interest in the interaction energy evaluation.
AB  - The membrane fouling behaviors of lysozyme (LYS) on three different membranes
      were systematically investigated during the membrane distillation (MD) process,
      including polypropylene (PP), polytetrafluoroethylene (PTFE) and polyvinylidene
      fluoride (PVDF) membranes. The results showed that PP membrane was not suitable
      for the MD operation due to its lower heat resistance. A flux decline of 50% was
      observed for the PTFE, while PVDF displayed a more severe decrement of 70%.
      Additionally, the PTFE and PVDF membranes both demonstrated a faster flux decline
      during the early period, and then a clear decrement of fouling rate was obtained
      at the later period. To better understand the interactions between LYS and
      different membranes, the interaction energy between LYS and the reconstructed
      membrane surface, represented by XDLVO potential, was calculated by surface
      element integration. The PVDF membrane exhibited higher roughness and lower
      energy barrier, indicating that rougher membrane was tended to be fouled by LYS.
      Finally, a "four stages model" was suggested for the MD fouling process, which
      was associated with three LYS deposition patterns of smooth, protuberance and
      valley.

PMID- 28433882
TI  - Hypothyroidism following allogeneic hematopoietic stem cell transplantation for
      acute myeloid leukemia.
AB  - BACKGROUND: Hypothyroidism may complicate allogeneic hematopoietic stem cell
      transplantation (allo-HSCT); we therefore analyzed risk factors in this study.
      PATIENTS AND METHODS: We studied 229 patients with acute myeloid leukemia (AML)
      who underwent an allo-HSCT between 2003 and 2013 with different conditioning
      regimens (myeloablative, reduced-intensity, chemotherapy-based, or total body
      irradiation-based). Thyroid-stimulating hormone (TSH) and free thyroxine levels
      (fT4) were available in 104 patients before and after allo-HSCT. RESULTS: The
      median age at transplantation (n=104) was 47 (IQR 40-59)], 37 (35.6%) patients
      were female, and the overall mortality was 34.6% (n=36). After a median follow-up
      period of 47 (IQR 25-84) months, overt hypothyroidism (basal TSH>4.49mIU/l,
      FT4<11.6pmol/l) was observed in 4 patients (3.8%) and subclinical hypothyroidism
      (basal TSH>4.49mIU/l, normal fT4) was observed in 20 patients (19.2%). Positive
      thyroperoxidase (TPO) antibodies were found in 5 (4.8%) patients. A total of 13
      patients (12.5%) were treated with thyroid hormone replacement. Acute graft
      versus-host disease (aGvHD) >=grade 2 occurred in 55 (52.9%) and chronic GvHD
      (cGvHD) in 74 (71.2%) of the patients. The risk of developing hypothyroidism was
      higher in the patients with repeated allo-HSCTs (P=0.024) and with positive TPO
      antibodies (P=0.045). Furthermore, the development of overt hypothyroidism was
      inversely proportional to age (P=0.043). No correlation was found with GvHD, HLA
      mismatch, total body irradiation, and gender. CONCLUSION: After allo-HSCT, a
      significant number of patients experience thyroid dysfunction, including
      subclinical and overt hypothyroidism. Long-term and continuous follow-up for
      thyroid function after HSCT is important to provide timely and appropriate
      treatment.

PMID- 28433883
TI  - Understanding the wettability of rough surfaces using simultaneous optical and
      electrochemical analysis of sessile droplets.
AB  - The interaction of a droplet with a solid surface is characterized by two
      parameters, the contact angle and the wetted area under the droplet. The Cassie
      Baxter and the Wenzel modes make predictions on the interfacial area by comparing
      the contact angles on smooth surfaces (the intrinsic wettability) with those on
      rough surfaces (the apparent wettability). In these models, the actual wetted
      area is used as a fitting parameter. In this work, we highlight the significance
      of determining the actual wetted area under the droplet and the limitation of
      using only the contact angle to represent the wetting behavior of a surface. Our
      experimental studies were performed on hydrophilic carbon surfaces where a
      combination of optical measurements (contact angle and hysteresis) along with an
      electrochemical approach was employed. An electrochemical method was used to
      determine the true wetted area using a droplet of aqueous electrolyte on the
      surface. The interfacial area was then used to correlate wetting behavior to that
      of the model predictions. We examined the impact of electrolyte concentration and
      potential sweep rate in our evaluation of the wetted area. Our results show that,
      for a rough hydrophilic surface, the decrease in contact angles with increasing
      solid-liquid interfacial areas is not always valid, as generally predicted by the
      Wenzel and the Cassie-Baxter models.

PMID- 28433884
TI  - Synthetic control of the size, shape, and polydispersity of anisotropic silica
      colloids.
AB  - The microstructure and rheological properties of colloidal suspensions depend on
      particle size and shape. This work aims to further control the size, shape, and
      polydispersity of anisotropic silica colloids, to reduce particle size, and to
      provide additional mechanistic insights on a prevalent, water-in-oil emulsion
      synthesis method. Key findings show that the dimensions of anisotropic silica
      particles can be systematically varied by approximately fivefold, with a limiting
      minimum particle size (D~60nm, L~300nm) obtained from emulsions with excess
      polyvinylpyrrolidone (PVP) and sodium citrate. The synthesis conditions are
      identified and discussed for which the emulsion composition, temperature,
      sonication, polymer entanglements, mixing, and other perturbations may induce or
      mitigate emulsion instabilities, citrate precipitation, a competing mechanism of
      templated growth, termination of anisotropic growth, irregular silica structures,
      and fiber formation. An improved mechanistic understanding will expand the
      roadmap for rational design and synthetic control of anisotropic colloids using
      sol-gel silica chemistry confined within water-in-oil emulsions.

PMID- 28433885
TI  - Electric fields within clay materials: How to affect the adsorption of metal
      ions.
AB  - Electric fields exist ubiquitously in chemical and biological systems while how
      to affect the interfacial adsorption processes remain elusive. Here, molecular
      dynamics simulations are used to understand at a molecular level the adsorption
      of metal ions at the interface of aqueous solutions and clay materials that are
      generally endowed with strong electric fields. In absence of electric fields,
      even Cs+, one of the strongest adsorbed metal ions, is facile to detach from
      solvated clay surfaces. Electric fields are critical to construct stable inner
      sphere complexes and enhance pronouncedly the adsorption strengths of both inner-
      and outer-sphere complexes. Heavy metal ions such as Pb2+ that are exclusively
      outer-sphere adsorbed are driven inner-sphere by electric fields, causing the
      adsorption strengths to surpass Cs+ and explaining partially the serious
      pollution to clay systems. Adsorption quantities of inner-sphere alkali ions
      increase with electric fields and in the case of Pb2+, are closely correlated
      with the intensities of electric fields. Previous models fail to account for
      Hofmeister effects occurring at solvated clay surfaces, and forceful supports are
      given to polarization effects that correctly interpret Hofmeister series
      (Cs+>Na+) and respond towards the change of electric fields.

PMID- 28433886
TI  - Controlled release of metformin from chitosan-based nanocomposite films
      containing mesoporous MCM-41 nanoparticles as novel drug delivery systems.
AB  - Biocompatible nanocomposite films based on blended chitosan and poly(ethylene
      glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (BP) polymers
      containing metformin (MET) drug and MCM-41 or MCM-41-APS (APS=aminopropylsilane)
      nanoparticles (NPs) were designed and fabricated in order to prepare novel drug
      delivery systems which are useful for controlled drug release purposes. The total
      pore volume and mesopore volume of MCM-41 were measured equal to 1.08 and 1.05
      cm3/g but those of MCM-41-APS were 0.54 and 0.26 cm3/g indicating smaller values
      for the APS functionalized material. The film thickness was the highest for CS-BP
      G-10%MET (70MUm) but it was the smallest for the CS-BP-G-4%MCM-41 (49MUm). For
      all of the films, the swelling percent was the highest in acidic medium but it
      was decreased in PBS and the least water uptake occurred in the alkaline
      environment. The lowest and the highest water uptake was observed for the films
      incorporated with 4%MCM-41NPs and 4%MCM-41-APS-10%MET, respectively. The SEM
      micrographs of the films after three days water uptake in pH=4 medium exhibited
      that all of the films were stable against cracking and/or tearing. It was found
      that increasing the MCM-41 or MCM-41-APS amount within the films decreased the
      elongation at break but enhanced the tensile stress. The release of the MET was
      sharply increased within ~22-24h (burst release) but after that the drug release
      was slowly enhanced during 15days (sustained release). Finally, it was concluded
      that the film 4% MCM-41-APS-10%MET NPs was the most promising drug delivery
      system because it had improved hydrophilicity, hydrolytic stability,
      biocompatibility, mechanical and drug release properties.

PMID- 28433887
TI  - Effects of clay art therapy on adults outpatients with major depressive disorder:
      A randomized controlled trial.
AB  - BACKGROUND: Depression has become a critical global health problem, affecting
      millions of people. Cost-effective nonpharmacological treatment in community
      settings has been proposed to complement medical treatment. Short-term clay art
      therapy (CAT) is an alternative treatment that promotes the enhancement of
      various aspects of mental health for depressed individuals. METHODS: One-hundred
      and six adults with depression were randomized into a CAT group or visual art
      (VA) control group for six 2.5-h weekly sessions. Intervention effects were
      measured using the Beck Depression Inventory, 12-Item General Health
      Questionnaire (Chinese version), Body-Mind-Spirit Well-Being Inventory, and 20
      Item Toronto Alexithymia Scale (Chinese version) at baseline, immediately
      postintervention (T1), and 3-weeks postintervention (T2). RESULT: Multivariate
      analysis of covariance results indicated a more significant time * group effect
      for CAT than for VA on depressive signs, general health, and body-mind-spirit
      well-being (all p<0.05). Significant within-groups changes were observed in these
      three aspects after treatment and at T2 (all p<0.001) and in alexithymia at T2
      (p<0.01) in the CAT group, but the change was nonsignificant in the VA group at
      T1 and T2. LIMITATIONS: The homogeneity of the participants affected the
      generalizability of the study findings. The short-term postintervention follow-up
      (3 weeks) presented difficulties in demonstrating the long-term effects of CAT.
      CONCLUSIONS: CAT can aid emotion regulation and benefit various aspects of mental
      health in adults. The short duration of the intervention suggests additional
      application value in treating depression. Further investigation is warranted
      regarding the potential effect of CAT on alleviating physical symptoms and
      improving social function.

PMID- 28433888
TI  - Plasma-derived exosomes contribute to inflammation via the TLR9-NF-kappaB pathway
      in chronic heart failure patients.
AB  - Exosomes are small vesicles that contain proteins, DNA and RNA, and play an
      important role in inflammation; however, the underlying mechanism remains
      unclear. In the present study, we found increased plasma-derived exosomes in
      chronic heart failure patients compared with healthy controls. Further, our data
      demonstrated that plasma-derived exosomes carried mtDNA, and triggered an
      inflammatory response via the TLR9-NF-kappaB pathway, as well, the inflammatory
      effect was closely related to exosomal mtDNA copy number. However, the effect
      could be blocked by chloroquine (CQ), a TLR9 inhibitor. These findings reveal a
      new mechanism of exosome-induced inflammation, and provide a new perspective for
      intervention and treatment of inflammation-related diseases, such as chronic
      heart failure.

PMID- 28433889
TI  - Quantitative proteomic profiling for clarification of the crucial roles of
      lysosomes in microbial infections.
AB  - Lysosomes play vital roles in both innate and adaptive immunity. It is widely
      accepted that lysosomes do not function exclusively as a digestive organelle. It
      is also involved in the process of immune cells against pathogens. However, the
      changes in the lysosomal proteome caused by infection with various microbes are
      still largely unknown, and our understanding of the proteome of the purified
      lysosome is another obstacle that needs to be resolved. Here, we performed a
      proteomic study on lysosomes enriched from THP1 cells after infection with
      Listeria monocytogenes (L.m), Herpes Simplex Virus 1 (HSV-1) and Vesicular
      Stomatitis Virus (VSV). In combination with the gene ontology (GO) analysis, we
      identified 284 lysosomal-related proteins from a total of 4560 proteins. We also
      constructed the protein-protein interaction networks for the differentially
      expressed proteins and revealed the core lysosomal proteins, including SRC in the
      L. m treated group, SRC, GLB1, HEXA and HEXB in the HSV-1 treated group and GLB1,
      CTSA, CTSB, HEXA and HEXB in the VSV treated group, which are involved in
      responding to diverse microbial infections. This study not only reveals variable
      lysosome responses depending on the bacterial or virus infection, but also
      provides the evidence based on which we propose a novel approach to proteome
      research for investigation of the function of the enriched organelles.

PMID- 28433890
TI  - IL-37 induces autophagy in hepatocellular carcinoma cells by inhibiting the
      PI3K/AKT/mTOR pathway.
AB  - Autophagy is an intracellular "self-eating" process that is closely related to
      inflammation and cellular immunity. New studies indicate that autophagy is also
      involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL
      37) has been shown to have tumor-suppressive abilities in hepatocellular
      carcinoma (HCC). Notably, autophagy appears to play a dual role in the
      development of HCC and may be involved in both tumorigenesis and tumor
      suppression. However, the potential role of IL-37 in autophagy is currently
      unknown. In this study, we investigated the effect of IL-37 on autophagy in
      multiple HCC cell lines. In doing so, we found that IL-37 inhibits proliferation
      in HCC cells and also induces autophagy and apoptosis in the SMMC-7721 and Huh-7
      cell lines. Further experiments revealed that IL-37 treatment reduced the levels
      of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of
      rapamycin (p-mTOR), phosphorylated p70 ribosomal protein s6 kinase (p-p70S6K) and
      phosphorylated 4E-binding protein 1 (4E-BP1). Moreover, treatment with an AKT
      agonist, insulin-like growth factor 1 (IGF-1), reversed these IL-37-mediated
      effects on autophagy, and treatment with an phosphoinositide-3-kinase (PI3K)/AKT
      inhibitor, LY294002, mimicked the effects of IL-37. Taken together, these results
      indicate that IL-37 regulates autophagy in SMMC-7721 and Huh-7 cells via
      inhibition of the PI3K/AKT/mTOR signaling pathway.

PMID- 28433891
TI  - Stakeholder driven indicators for eHealth performance management.
AB  - The goal of the present article is to compile a corpus of indicators of eHealth
      development evaluation that would essentially reflect stakeholder approaches and
      complement technical indicators of assessment of an eHealth system. Consequently,
      the assessment of the development of an eHealth system would reflect stakeholder
      approaches and become an innovative solution in attempting to improve
      productivity of IT projects in the field of health care. The compiled minimum set
      of indicators will be designed to monitor implementation of the national eHealth
      information system. To ensure reliability of the quality research, the
      respondents were grouped in accordance to the geographical distribution and
      diversity of the levels and types of the represented jobs and institutions. The
      applied analysis implies several managerial insights on the hierarchy of eHealth
      indicators. These insights may be helpful in recommending priority activities in
      implementation of an eHealth data system on the national or international level.
      The research is practically useful as it is the first to deal with the topic in
      Lithuania and its theoretical and practical aspect are particularly relevant in
      implementation of an eHealth data system in Lithuania. The eHealth assessment
      indicators presented in the article may be practically useful in two aspects: (1)
      as key implementation guidelines facilitating the general course of eHealth
      system development and (2) as a means to evaluate eHealth outcomes.

PMID- 28433892
TI  - Longitudinal associations between the use of sexually explicit material and
      adolescents' attitudes and behaviors: A narrative review of studies.
AB  - This review analyzed longitudinal studies examining the effects of sexually
      explicit material on adolescents' attitudes, beliefs and behaviors. The review
      also aimed to provide an analysis of the limitations of the existing studies, as
      well as recommendations for future research. To be included, publications had to
      employ repeated measurements, include a measure of sexually explicit material use
      and participants aged 18 years or under. A total of 20 papers from nine different
      research projects were reviewed. The results show that sexually explicit material
      is associated with sexual behavior, sexual norms and attitudes, gender attitudes,
      self-esteem, sexual satisfaction, uncertainty and preoccupancy. In addition, the
      studies reported developmental effects on adolescents' behavioral, cognitive and
      emotional well-being. Because experimental studies among adolescents are not
      feasible, more methodologically rigorous longitudinal studies-followed by a meta
      analysis-are needed to further our understanding of the effects of sexually
      explicit material in this population.

PMID- 28433893
TI  - Cytokine profile in chronic hepatitis C: An observation.
AB  - The data addressing cytokine profile in chronically infected HCV patients are
      conflicting, ranging from Th1 or Th2 cytokine prevalence to the expression of
      both types of cytokines. Therefore, the aim of this study was to evaluate
      cytokine profile in these patients. Cytokine sera levels in HCV patients and
      healthy controls were evaluated using 13plex FlowCytomix Multiplex. Median values
      of both proinflammatory and anti-inflammatory cytokines were lower in HCV
      patients then in controls. In addition, the number of subjects producing
      detectable quantities of cytokines was significantly lower in the group of HCV
      patients. Yet, cytokine levels in those patients were remarkably heterogeneous
      ranging from low to extremely high, much higher than the maximal values in
      control group. Similarly, grouping data according to HCV genotype, HCV RNA load,
      ALT/AST ratio and the stage of fibrosis showed marked standard deviations,
      reflecting high intragroup diversity. No correlation was found between each
      disease-related factor and cytokine levels. Patients investigated in our and
      similar studies were disparate pursuant to characteristics of the hosts, pathogen
      and course of the disease. Therefore, the inconsistency of the literature data
      regarding cytokine pattern in chronic HCV patients may be a consequence of the
      disregarded/overlooked heterogeneity of these patients.

PMID- 28433894
TI  - A functional SNP MCP-1 (-2518A/G) predispose to renal disorder in Indian Systemic
      Lupus Erythematosus patients.
AB  - Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous chronic,
      inflammatory autoimmune disorder that affects multiple organs where exact
      etiology of the disease is not yet clearly understood. Various evidences suggest
      that genetic polymorphisms in inflammatory mediators like cytokines and
      chemokines may influence development of the disease. Here, we investigated
      whether functional polymorphism at the Monocyte Chemoattractant Protein-1 (MCP-1)
      regulatory region associates with disease phenotype in Indian SLE patients. This
      case control study included 200 SLE patients and 201 ethnically matched healthy
      controls. Genotyping of MCP-1 (-2518 A/G) polymorphism was performed using PCR
      RFLP method. Serum MCP-1 levels were detected by bead-based multiplex
      immunoassay. Serum MCP-1 levels were found to be higher in patients compared with
      healthy individuals (p<0.0001). A significant difference for MCP-1G allele
      frequency (OR=1.9, 95%CI=1.4-2.6, p<0.0001) was observed among SLE patients
      against healthy individuals. A significant difference in the distribution of MCP
      1 -2518GG (OR=3.0, 95%CI=1.4-6.7, p=0.0041) and AG+GG genotypes (OR=2.0,
      95%CI=1.4-3.0, p=0.0005) was also noted among SLE patients when compared with
      healthy individuals. A significant association was observed between A/G and G/G
      versus A/A genotypes with renal manifestations (p<0.0001, Pc<0.001). Serum MCP-1
      levels in active LN patients were found to be significantly higher than inactive
      LN (p=0.0059), mild LN (p=0.0061) as well as non-LN patients (p=0.0001). These
      findings suggest that -2518G allele of MCP-1 -2518 A/G polymorphism is associated
      with renal disorders and may influence MCP-1 gene expression among Indian SLE
      patients.

PMID- 28433895
TI  - Evaluating network-level predictors of behavior change among injection networks
      enrolled in the HPTN 037 randomized controlled trial.
AB  - BACKGROUND: Little is known about ways network-level factors that may influence
      the adoption of combination prevention behaviors among injection networks, or how
      network-oriented interventions might moderate this behavior change process.
      METHODS: A total of 232 unique injection risk networks in Philadelphia, PA, were
      randomized to a peer educator network-oriented intervention or standard of care
      control arm. Network-level aggregates reflecting the injection networks' baseline
      substance use dynamics, social interactions, and the networks exposure to gender-
      and structural-related vulnerabilities were calculated and used to predict
      changes in the proportion of network members adopting safer injection practices
      at 6-month follow-up. RESULTS: At follow-up, safer injection practices were
      observed among 46.31% of a network's members on average. In contrast, 25.7% of
      networks observed no change. Controlling for the effects of the intervention,
      significant network-level factors influencing network-level behavior change
      reflected larger sized injection networks (b=2.20, p=0.013) with a greater
      proportion of members who shared needles (b=0.29, p<0.001) and engaged in poly
      drug use at baseline (b=6.65, p=0.021). Changes in a network's safer injection
      practices were also observed for networks with fewer new network members (b=
      0.31, p=0.008), and for networks whose members were proportionally less likely to
      have experienced incarceration (b=-0.20, p=0.012) or more likely to have been
      exposed to drug treatment (b=0.17, p=0.034) in the 6-months prior to baseline. A
      significant interaction suggested the intervention uniquely facilitated change in
      safer injection practices among female-only networks (b=-0.32, p=0.046).
      CONCLUSIONS: Network-level factors offer insights into ways injection networks
      might be leveraged to promote combination prevention efforts.

PMID- 28433896
TI  - In-situ sludge pretreatment in a single-stage anaerobic digester.
AB  - This study aimed to develop an in-situ sludge pretreatment method by increasing
      the temperature from thermophilic to extreme thermophilic condition in a single
      stage anaerobic digester. The results revealed that a stable performance was
      obtained within the temperature range of 55-65 degrees C, and the maximum methane
      yield of 208.51+/-13.66mL/g VS was obtained at 65 degrees C. Moreover, the
      maximum extent of hydrolysis (33%) and acidification (27.1%) was also observed at
      65 degrees C. However, further increase of temperature to 70 degrees C did not
      improve the organic conversion efficiency. Microbial community analysis revealed
      that Coprothermobacter, highly related to acetate oxidisers, appeared to be the
      abundant bacterial group at higher temperature. A progressive shift in
      methanogenic members from Methanosarcina to Methanothermobacter was observed upon
      increasing the temperature. This work demonstrated single-stage sludge digestion
      system can be successfully established at high temperature (65 degrees C) with
      stable performance, which can eliminate the need of conventional thermophilic
      pretreatment step.

PMID- 28433897
TI  - Low temperature microwave-assisted pyrolysis of wood sawdust for phenolic rich
      compounds: Kinetics and dielectric properties analysis.
AB  - Microwave-assisted pyrolysis of wood sawdust for phenolic rich compounds was
      carried out between 400 and 550 degrees C in a batch reactor. An efficient
      preparation of liquid products was observed at 500 degrees C with a yield of
      58.50%, which was similar to conventional fast pyrolysis. The highest
      concentration of phenolic compounds in liquid product reached up to 78.7% (area)
      in which the alkoxy phenols contributed 81.8% at 500 degrees C. Microwave
      thermogravimetric analysis using KAS method was used firstly to investigate the
      low-temperature pyrolytic behaviors and activation energy. The results indicated
      that effective pyrolytic range was 250-400 degrees C and average activation
      energy was 42.78kJ/mol, which were 50-100 degrees C and 50-100kJ/mol lower than
      conventional pyrolysis, respectively. Analysis on dielectric properties of
      pyrolytic products confirmed that accelerated pyrolysis and low temperature were
      attributed to the formation of instantaneous "hot spots".

PMID- 28433898
TI  - Performance and microbial population dynamics during stable operation and
      reactivation after extended idle conditions in an aerobic granular sequencing
      batch reactor.
AB  - The evolution of removal performance and bacterial population dynamics of an
      aerobic granular sequencing batch reactor were investigated during stable
      operation and reactivation after prolonged storage. The system was run for a
      period of 130days including the stable condition phase, storage period and the
      subsequent reactivation process. Excellent removal performance was obtained
      during the stable operation period, which was decayed by the extended idle
      conditions. The removal efficiencies for both carbon and nitrogen decayed while
      phosphorus removal remained unaffected. Both granules structure and physical
      properties could be fully restored. Microbial populations shifted sharply and the
      storage perturbations irreversibly altered the microbial communities at different
      levels. Extracellular polymeric substances (especially protein) and key groups
      were identified as contributors for storage and re-startup of the aerobic
      granular system.

PMID- 28433899
TI  - Sustainable production of a new generation biofuel by lipase-catalyzed
      esterification of fatty acids from liquid industrial waste biomass.
AB  - In this work we suggest a methodology comprising the design and use of cost
      effective, sustainable, and environmentally friendly process for biofuel
      production compatible with the market demands. A new generation biofuel is
      produced using fatty acids, which were generated from acidogenesis of industrial
      wastes of bioethanol distilleries, and esterified with selected alcohols by
      immobilized Candida antarctica Lipase-B. Suitable reactors with significant
      parameters and conditions were studied through experimental design, and novel
      esterification processes were suggested; among others, the continuous removal of
      the produced water was provided. Finally, economically sustainable biofuel
      production was achieved providing high ester yield (<97%) along with augmented
      concentration (3.35M) in the reaction mixtures at relatively short esterification
      times, whereas the immobilized lipase maintained over 90% of its initial
      esterifying ability after reused for ten cycles.

PMID- 28433900
TI  - Production of new human milk fat substitutes by enzymatic acidolysis of
      microalgae oils from Nannochloropsis oculata and Isochrysis galbana.
AB  - Human milk fat substitutes (HMFs) with four kinds of n-3 fatty acid for infant
      formula were firstly synthesized using triacylglycerols (TAGs) from
      Nannochloropsis oculata rich in PA at the sn-2 position and free fatty acids
      (FFAs) from Isochrysis galbana rich in n-3 polyunsaturated fatty acids (n-3 PUFAs
      ALA/SDA/DHA) via solvent-free acidolysis with Novozym 435, Lipozyme 435, TL-IM
      and RM-IM as biocatalysts. The results show that the resulting HMFs contain total
      n-3 PUFA of 13.92-17.12% and PA of 59.38-68.13% at the sn-2 position under the
      optimal conditions (mole ratio FFAs/TAG 3:1, 60 degrees C (Novozym 435 and
      Lipozyme TL-IM) and 50 degrees C (Lipozyme 435 and RM-IM), lipase loading 10%,
      reaction time 24h). Moreover, among the tested enzymes, Lipozyme 435, TL-IM, and
      RM-IM display the fatty acid selectivity towards SDA, LA and ALA, and OA,
      respectively. Overall, the examined lipases are promising biocatalysts for
      producing high-value microalgal HMFs in a cost-effective manner.

PMID- 28433901
TI  - Significantly enhanced enzymatic hydrolysis of rice straw via a high-performance
      two-stage deep eutectic solvents synergistic pretreatment.
AB  - A two-stage deep eutectic solvents (DESs) treatment was shown to be an effective
      method for improving the utilization of certain DESs, and the specific order of
      pretreatment, such as malic acid/proline (MP) or choline chloride/oxalic acid
      (CO) during the first stage and choline chloride/urea (CU) during the second
      stage, resulted in better performance for enhancing the sugar yield due to the
      synergistic effect of the two DESs on biomass fractionation. Moreover, the
      presence of water during these processes could balance the loss of components by
      tuning the pretreatment severity, thus ensuring higher sugar yields. By
      eliminating the washing step after the first stage treatment, enhanced cellulose
      recovery and glucose yield were achieved for the CO-CU pretreatment in the
      presence of 5% water, and a simpler process was established with a glucose yield
      of 90.2% after a 3-h treatment at 100 degrees C.

PMID- 28433902
TI  - Evaluation of different types of anaerobic seed sludge for the high rate
      anaerobic digestion of pig slurry in UASB reactors.
AB  - Three different types of anaerobic sludge (granular, thickened digestate and
      anaerobic sewage) were evaluated as seed inoculum sources for the high rate
      anaerobic digestion of pig slurry in UASB reactors. Granular sludge performance
      was optimal, allowing a high efficiency process yielding a volumetric methane
      production rate of 4.1LCH4L-1d-1 at 1.5days HRT (0.248LCH4g-1COD) at an organic
      loading rate of 16.4gCODL-1d-1. The thickened digestate sludge experimented
      flotation problems, thus resulting inappropriate for the UASB process. The
      anaerobic sewage sludge reactor experimented biomass wash-out, but allowed high
      process efficiency operation at 3days HRT, yielding a volumetric methane
      production rate of 1.7LCH4L-1d-1 (0.236LCH4g-1COD) at an organic loading rate of
      7.2gCODL-1d-1. To guarantee the success of the UASB process, the settleable
      solids of the slurry must be previously removed.

PMID- 28433903
TI  - One-step production of biodiesel from wet and unbroken microalgae biomass using
      deep eutectic solvent.
AB  - One-step and Two-step methods were studied for lipid extraction from wet and
      unbroken (water content is 65-67%) Chlorella sp. and Chlorococcum sp. (GN38)
      using deep eutectic solvent (DES) treated microalgae cells. Further we optimized
      the extraction process and studied on its underlying mechanism. Among all DES,
      Choline chloride-Acetic acid (Ch-Aa) DES treatment showed optimal conditions at
      the mass ratio of DES: methanol-H2SO4 (2.00%) mixture: algae biomass was 60:40:3
      with reaction time was 60min, and the optimum temperature was 110 degrees C
      (Chlorococcum sp.) and 130 degrees C (Chlorella sp.) respectively. The total
      content of FAME by One-step method with DES treatment was improved by 30%
      compared with Two-step method. This process is effective on wet and unbroken
      paste of microalgae biomass, so the FAME extracted using one-step with DES
      process is feasible for microalgae based biodiesel production.

PMID- 28433904
TI  - Biodegradation of naproxen by freshwater algae Cymbella sp. and Scenedesmus
      quadricauda and the comparative toxicity.
AB  - Naproxen is one of the most prevalent pharmaceuticals and of great environment
      concern. Information about bioremediation of naproxen by algae remains limited
      and no study has been reported on the degradation mechanism and the toxicity of
      NPX on algae. In this study, both Cymbella sp. and Scenedesmus quadricauda showed
      complete growth inhibition (100%) at 100mgL-1 within 24h. Biochemical
      characteristics including chlorophyll a, carotenoid contents and enzyme
      activities for these two microalgae were affected by NPX at relatively high
      concentrations after 4d of exposure. Degradation of naproxen was accelerated by
      both algae species. Cymbella sp. showed a more satisfactive effect in the
      bioremediation of NPX with higher removal efficiency. A total of 12 metabolites
      were identified by LC-MS/MS and the degradation pathways of naproxen in two algae
      were proposed. Hydroxylation, decarboxylation, demethylation, tyrosine
      conjunction and glucuronidation contributed to naproxen transformation in algal
      cells.

PMID- 28433905
TI  - Pretreating wheat straw by phosphoric acid plus hydrogen peroxide for enzymatic
      saccharification and ethanol production at high solid loading.
AB  - Wheat straw was pretreated by phosphoric acid plus hydrogen peroxide (PHP) for
      enzymatic hydrolysis and ethanol fermentation at high solid loadings. Results
      indicated solid loading could reach 20% with 77.4% cellulose-glucose conversion
      and glucose concentration of 164.9g/L in hydrolysate, it even was promoted to 25%
      with only 3.4% decrease on cellulose-glucose conversion as the pretreated-wheat
      straw was dewatered by air-drying. 72.9% cellulose-glucose conversion still was
      achieved as the minimized enzyme input of 20mg protein/g cellulose was employed
      for hydrolysis at 20% solid loading. In the corresponding conditions, 100g wheat
      straw can yield 11.2g ethanol with concentration of 71.2g/L by simultaneous
      saccharification and fermentation. Thus, PHP-pretreatment benefitted the glucose
      or ethanol yield at high solid loadings with lower enzyme input. Additionally,
      decreases on the maximal cellulase adsorption and the direct-orange/direct-blue
      indicated drying the PHP-pretreated substrates negatively affected the hydrolysis
      due to the shrinkage of cellulase-size-accommodable pores.

PMID- 28433906
TI  - Treatment of urban sludge by hydrothermal carbonization.
AB  - Urban sludge was treated by Hydrothermal carbonization (HTC). The effect of
      hydrothermal carbonization temperature, mixing with or without catalysts on solid
      products yield, heavy metal contents, turbidity and COD value was evaluated. The
      result showed solid products yield decreased from 92.04% to 52.65% when the
      temperature increased from 180 to 300 degrees C. And the Cu, Zn, and Pb contents
      under exchangeable states decreased and reached discharge standard. Addition of
      FeCl3 or Al(OH)3 resulted in a significant increase in the exchangeable states of
      Zn, Pb, Cr, and Cd and decrease in their residual states. The turbidity and COD
      value of hydrothermal liquid decreased from 450 degrees  to 175 degrees , and 13
      to 6.8g/L, with increasing hydrothermal temperature. Comparison with HTC, solid
      productivity from low-temperature pyrolysis is higher. The exchangeable states of
      Cu, Zn, and Cr exceeded the limiting values. Our results show HTC can facilitate
      transforming urban sludge into no-pollution and energy-rich products.

PMID- 28433907
TI  - Rapid generation of volatile fatty acids (VFA) through anaerobic acidification of
      livestock organic waste at low hydraulic residence time (HRT).
AB  - The purpose of this study was to investigate the effect of pre-treatment and F/M
      (Food to Microorganism) ratios for the rapid generation of volatile fatty acids
      (VFA) from livestock organic wastes (cattle manure (CM) and poultry litter (PL))
      through an anaerobic acidification process at a pH range of 4.5-5.5. Experiments
      were organized using CM and PL in batch reactors (1L and 25L) with and with no
      pre-treatment of substrate at F/M ratios (0.4, 0.6, 0.8 and 1). Among various
      existing pre-treatments methods, thermal-acidic (120 degrees C; 1% H2SO4) pre
      treatment was found effective. The results revealed that 0.31 and 0.47kg VFA/(kg
      VS reduced) could be obtained from CM and PL respectively with no pre-treatment,
      whereas it improvised to 0.43 and 0.67kg VFA/(kg VS reduced) correspondingly due
      to pre-treatment. Aforesaid, better yield of VFA was obtained at F/M ratio of
      1.0, pH-5.5 and hydraulic residence time of 4days.

PMID- 28433908
TI  - Steam torrefaction of Eucalyptus globulus for producing black pellets: A pilot
      scale experience.
AB  - Steam torrefaction of Eucalyptus globulus was performed at temperatures between
      245 degrees C and 265 degrees C in a 100kg/h pilot plant. Torrefied biomass was
      then pelletized in a 300kg/h unit and the pellets were subject to durability,
      density and combustion tests. The structural changes measured with FTIR were
      studied along with the combustion behavior of the materials. Compositional
      analysis showed that increasing the torrefaction temperature reduced both
      hemicellulose fraction and overall mass yield (MY). Furthermore, there was a
      linear relationship between the energy yield (EY) and mass yield (EY=[1.04-0.9(1
      MY)]) for these samples. The ignition and comprehensive indexes confirmed that
      the stability of the torrefied biomass in a combustion environment was higher
      than for untreated biomass. Finally, pellets showed high durability (98%), and
      had an energy density (13-14GJ/m3), which is comparable to low-rank coals.

PMID- 28433909
TI  - Culturing of Selenastrum on diluted composting fluids; conversion of waste to
      valuable algal biomass in presence of bacteria.
AB  - Growth and fatty acid production of microalga Selenastrum sp. with associated
      bacteria was studied in lab-scale experiments in three composting leachate
      liquids. Nutrient reduction in cultures was measured at different initial
      substrate strengths. A small, pilot-scale photobioreactor (PBR) was used to
      verify lab-scale results. Similar growth conditions supported growth of both
      Selenastrum and bacteria. CO2 feed enhanced the production of biomass and lipids
      in PBR (2.4gL-1 and 17% DW) compared to lab-scale (0.1-1.6gL-1 and 4.0-6.5% DW)
      experiments. Also prolonged cultivation time increased lipid content in PBR. At
      both scales, NH4-N with an initial concentration of ca. 40mgL-1 was completely
      removed from the biowaste leachate. In lab-scale, maximal COD reduction was over
      2000mgL-1, indicating mixotrophic growth of Selenastrum. Co-cultures are
      efficient in composting leachate liquid treatment, and conversion of waste to
      biomass is a promising approach to improve the bioeconomy of composting plants.

PMID- 28433910
TI  - Succinic acid production by immobilized cultures using spent sulphite liquor as
      fermentation medium.
AB  - Spent sulphite liquor (SSL) was used as carbon source for the production of
      succinic acid using immobilized cultures of Actinobacillus succinogenes and
      Basfia succiniciproducens on two different supports, delignified cellulosic
      material (DCM) and alginate beads. Fed-batch immobilized cultures with A.
      succinogenes in alginates resulted in higher sugar to succinic acid conversion
      yield (0.81g/g) than the respective yield achieved (0.65g/g) when DCM immobilized
      cultures were used. The final succinic acid concentration and yield achieved in
      fed-batch with immobilized cultures of B. succiniciproducens in alginates (45g/L
      and 0.66g/g) were higher than A. succinogenes immobilized cultures (35.4g/L and
      0.61g/g) using nano-filtrated SSL as fermentation medium. Immobilized cultures of
      B. succiniciproducens in alginate beads were reused in four sequential fed-batch
      fermentations of nano-filtrated SSL leading to the production of 64.7g of
      succinic acid with a yield range of 0.42-0.67g/g and productivity range of 0.29
      0.65g/L/h. The immobilized cultures improved the efficiency of succinic acid
      production as compared to free cell cultures.

PMID- 28433911
TI  - Enhanced nitrogen removal by membrane-aerated nitritation-anammox in a
      bioelectrochemical system.
AB  - A bioelectrochemical system (BES) containing membrane-aerated nitritation-anammox
      in its cathode has been developed for enhancing nitrogen removal. Long-term
      performance and microbial community structure were investigated. The BES using
      loop operation and external voltage achieved the highest total nitrogen removal
      efficiency of 94.8+/-7.7%, and COD removal of 98.2+/-3.3% at hydraulic retention
      time of 60h and the lumen pressure of 10psi. The energy consumption of the system
      was 0.90kWhkgN-1 or 0.38kWhkg COD-1. Sequencing analyses revealed that ammonia
      oxidizing bacteria (0.2-7.4%), anammox bacteria (0.4-10.3%), denitrifying
      bacteria (5.8-13.1%), and electrogenic bacteria (4.6-12.8%) were in abundance of
      the microbial community in the cathode chamber, and their distributions were
      affected by the aeration and physical locations. These results encourage further
      investigation of membrane-aerated nitritation-anammox in BES for optimization and
      potential applications with actual wastewater.

PMID- 28433912
TI  - Achieving partial denitrification through control of biofilm structure during
      biofilm growth in denitrifying biofilter.
AB  - Partial denitrification was one of most effective ways to provide nitrite for
      annamox; whereas very limited research has been done to achieve nitrite
      accumulation in biofilm system. In this study, partial denitrification was
      studied in a lab-scale denitrifying biofilter (DNBF). The results showed biofilm
      structure variations caused the differences between nitrate specific reduction
      rate (NaSRR) and nitrite specific reduction rate (NiSRR), which led to nitrite
      accumulation in different degree at different biofilm formation phases.
      Hydrodynamic conditions also significantly influenced biofilm structure, nitrate
      and nitrite reduction activities. At the filtration velocity of 3.86mh-1, not
      only biofilm structure, NaSRR and NiSRR kept relatively stable, but also 60% of
      nitrite accumulation and no nitrate in the effluent were achieved. Furthermore,
      Thauera genus bacteria, benefited for nitrite accumulation, became the dominant
      communities in high nitrite accumulation conditions. The partial denitrification
      combine with anammox in biofilter have the great potential applied in WWTPs.

PMID- 28433913
TI  - Simultaneous partial nitrification and 2-fluorophenol biodegradation with aerobic
      granular biomass: Reactor performance and microbial communities.
AB  - An aerobic granular bioreactor was operated for over 4months, treating a
      synthetic wastewater with a high ammonium content (100mgNL-1). The inoculum was
      collected from a bioreactor performing simultaneous partial nitrification and
      aromatic compounds biodegradation. From day-56 onwards, 2-fluorophenol (2-FP)
      (12.4mgL-1) was added to the feeding wastewater and the system was bioaugmented
      with a 2-FP degrading bacteria (Rhodococcus sp. FP1). By the end of operation,
      complete 2-FP biodegradation and partial nitrification were simultaneously
      achieved. Aerobic granules remained stable over time. During the 2-FP loading, a
      shift in the community structure occurred, coinciding with the improvement of 2
      FP degradation. DGGE analysis did not allow to infer on the bioaugmented strain
      presence but pyrosequencing analysis detected Rhodococcus genus by the end of
      operation. Together with other potential phenolic-degraders within granules,
      these microorganisms were probably responsible for 2-FP degradation.

PMID- 28433914
TI  - Accumulation of sugar from pulp and xylitol from xylose by pyruvate decarboxylase
      negative white-rot fungus Phlebia sp. MG-60.
AB  - Phlebia sp. MG-60 is a white-rot fungus that produces ethanol with high
      efficiency from lignocellulosic biomass without additional enzymes. Through
      engineering of this powerful metabolic pathway for fermentation in Phlebia sp. MG
      60, chemical compounds other than ethanol could be produced. Here, we demonstrate
      sugar accumulation from unbleached hardwood kraft pulp and conversion of xylose
      to xylitol by pyruvate decarboxylase (pdc)-negative Phlebia sp. MG-60. We
      isolated Phlebia sp. strain MG-60-P2 from protoplasts to unify the protoplast
      phenotypes of the regenerated strains. Homologous recombination achieved a stable
      pdc-knockout line, designated KO77. The KO77 line produced traces of ethanol, but
      accumulated xylitol from xylose or glucose from unbleached hardwood kraft pulp.
      These metabolic changes in the pdc-knockout strain reflect the potential of
      metabolic engineering in Phlebia sp. MG-60 for direct production of chemical
      compounds from lignocellulosic biomass.

PMID- 28433915
TI  - Stimulation of the anaerobic digestion of the dry organic fraction of municipal
      solid waste (OFMSW) with carbon-based conductive materials.
AB  - Growth of bacterial and archaeal species capable of interspecies electron
      exchange was stimulated by addition of conductive materials (carbon cloth or
      granular activated carbon (GAC)) to anaerobic digesters treating dog food (a
      substitute for the dry-organic fraction of municipal solid waste (OFMSW)).
      Methane production (772-1428mmol vs <80mmol), volatile solids removal (78%-81% vs
      54%-64%) and COD removal efficiencies (~80% vs 20%-30%) were all significantly
      higher in reactors amended with GAC or carbon cloth than controls. OFMSW
      degradation was also significantly accelerated and VFA concentrations were
      substantially lower in reactors amended with conductive materials. These results
      suggest that both conductive materials (carbon cloth and GAC) can promote
      conversion of OFMSW to methane even in the presence of extremely high VFA
      concentrations (~500mM).

PMID- 28433916
TI  - A novel method for contributing to composting start-up at low temperature by
      inoculating cold-adapted microbial consortium.
AB  - Low temperature climate presented a technical challenge to start-up composting in
      northern region of China. This study investigated if the cold-adapted microbial
      consortium (CAMC) could promote composting start-up at low temperature. In this
      work, the CAMC was inoculated when food waste was composted at 10 degrees C. The
      results showed that inoculating CAMC accelerated the piles temperature
      effectively, the piles passed through the start-up period within 37h. Moreover,
      the inoculants could enhance the abundances of dominant strains related to
      organic matters degradation rate. Redundancy analysis (RDA) indicated that the
      relationships among indigenous bacteria, organic substrates degradation and
      temperature evolution were influenced by the inoculants. Furthermore, the heat
      generation value and degradation rate of the hydrolysable carbohydrate, lipids
      and protein were significantly enhanced with CAMC inoculated. This work
      demonstrated that inoculating CAMC was beneficial to composting self-heating, it
      provided a novel biotechnology support to ensure the normal start-up of winter
      composting.

PMID- 28433917
TI  - Hydrothermal carbonisation of poultry litter: Effects of initial pH on yields and
      chemical properties of hydrochars.
AB  - In this study, hydrothermal carbonisation (HTC) of poultry litter (PL) was
      carried out to evaluate the impact of initial pH using acetic acid (CH3COOH) or
      sulfuric acid (H2SO4) on the yields and properties of hydrochar (HC). The PL
      samples were treated by HTC at various initial pH and at 250 degrees C for 2h.
      The HCs produced were characterized by ultimate, proximate and fibre analyses as
      well as heating value and surface area measurements. The results indicated that
      undertaking HTC in the presence of acids (CH3COOH, H2SO4) significantly affects
      the yields and properties of HC. The C content and HHV of the HC increased with
      decreasing initial pH. In the presence of H2SO4, the hydrochar yield (HY)
      increased while the ash content was significantly reduced. The lowest ash content
      and the highest HY were measured in the HC produced from the suspension with an
      initial pH of 2 using H2SO4.

PMID- 28433918
TI  - Chronic responses of aerobic granules to zinc oxide nanoparticles in a sequencing
      batch reactor performing simultaneous nitrification, denitrification and
      phosphorus removal.
AB  - The reactor performance, granules characteristics and microbial population
      dynamics were investigated to assess the chronic responses of aerobic granules to
      zinc oxide nanoparticles (ZnO NPs) of 0, 5, 10 and 20mg/L for a period of
      180days. The results showed that ZnO NPs stimulated COD removal, whereas caused
      inhibition to both nitrification and denitrification. However, biological
      phosphorus removal remained effective and stable. Introduction of ZnO NPs sharply
      decreased the respiration of granules, while did not change the settleability.
      Both content of extracellular polymeric substances (EPS) and the ratio of protein
      to polysaccharides (PN/PS) rose significantly. MiSeq pyrosequencing was employed
      to explore the microbial population dynamics. Results demonstrated that up to
      20mg/L reduced the alpha-diversity of bacterial communities. Finally,
      phylogenetic classification of the dominant functional species involved in
      biological nutrients removal were identified to assess the effects of ZnO NPs to
      aerobic granules from the molecular level.

PMID- 28433919
TI  - Identification of differentially expressed miRNAs through high-throughput
      sequencing in the chicken lung in response to Mycoplasma gallisepticum HS.
AB  - Mycoplasma gallisepticum (MG) infects chickens, causes chronic respiratory
      diseases (CRD) and severely damages the poultry industry. It has been suggested
      that micro-ribonucleic acids (miRNAs) are involved in microbial pathogenesis.
      Here, we identified miRNAs that are associated with MG infection in chicken lungs
      at 3 and 10days post-infection by deep sequencing. Thirty-six down-regulated and
      9 up-regulated miRNAs belonging to 31 miRNA families were detected at 3days post
      infection, whereas 50 down-regulated and 18 up-regulated miRNAs belonging to 41
      miRNA families were found at 10days post-infection. The 45 and 68 differentially
      expressed miRNAs at 3 and 10days target 6280 and 7181 genes, respectively. In
      this study, 8 candidate novel chicken miRNAs were identified. Analyses via GO,
      KEGG, miRNA-GO-network, path-net and gene-net showed that these altered miRNAs
      might be involved in regulating the host response to MG infection by targeting
      genes in many pathways, such as the MAPK pathway, focal adhesion, Wnt pathway,
      endocytosis, Jak/STAT pathway, phosphatidylinositol pathway, adherens junctions,
      regulation of actin cytoskeleton among others. These analyses indicate that the
      MAPK pathway may be a key regulatory route. Also, the miR-8 family, miR-499
      family, miR-17 family, and PIK3 family genes, as well as the MAP2K1 and RAC1
      genes, might be important in MG infection. miR-20 of the miR-17 family was
      further confirmed by RT-qPCR. The important miRNAs, mRNAs and pathways associated
      with MG infection in chicken are valuable for further research. Our data provide
      new insights into the mechanism of these miRNAs on the regulation of host-MG
      interactions.

PMID- 28433920
TI  - Proteomic analysis of sockeye salmon serum as a tool for biomarker discovery and
      new insight into the sublethal toxicity of diluted bitumen.
AB  - Pipelines carrying diluted bitumen (dilbit) from Canada's oil sands traverse
      North America, including the freshwater habitat of Pacific salmon, posing a risk
      of environmental release and aquatic exposure. Swimming performance is impacted
      in juvenile sockeye (Oncorhynchus nerka) exposed to dilbit; therefore biomarkers
      of dilbit exposure will be valuable for monitoring at-risk salmon stocks. This
      study characterized changes in the serum proteome of sockeye exposed to a sub
      lethal and environmentally relevant concentration of dilbit using isobaric tags
      for relative and absolute quantitation (iTRAQ), and included a range of
      experimental conditions to permit identification of biomarkers that are robust
      across time (1 and 4wk) and exercise level (at rest and following a swim test).
      Over 500 proteins were identified and quantified in sockeye serum, with dilbit
      exposure significantly altering the abundance of 24 proteins irrespective of time
      and exercise, including proteins associated with immune and inflammatory
      responses, coagulation, and iron homeostasis. An increase in creatine kinase (CK)
      activity in serum of dilbit-exposed salmon confirmed the higher CK protein
      abundance measured using iTRAQ. The combination of 4wk dilbit exposure and a swim
      test had a greater effect on the serum proteome than either treatment alone,
      including a marked increase in tissue leakage proteins, suggesting that aerobic
      exercise exacerbates the serum proteome response to dilbit, and the increased
      cellular damage could impede exercise recovery. This study provides a foundation
      for the development of bio-monitoring tools for salmon stock assessments, and
      offers new insights into the sub-lethal toxicity of crude oil exposure in fish.

PMID- 28433921
TI  - A contribution to the phylogeny of agglutinating Arcellinida (Amoebozoa) based on
      SSU rRNA gene sequences.
AB  - Arcellinid testate amoebae include a wide variety of amoeboid organisms whose
      test (shell) varies in shape, composition and size. A decade ago, we initiated
      molecular phylogenetic analyses based on SSU rRNA gene sequences and a taxonomic
      revision of Arcellinida. However, many lineages within Arcellinida still lack
      molecular data, and the phylogeny of this group is largely incomplete. In this
      study, we obtained SSU rRNA gene sequences from seven taxa, of which six have
      agglutinated shell (Difflugia oblonga, D. labiosa, D. gramen, Mediolus corona,
      Netzelia wailesi, and N. tuberculata), and one has an entirely proteinaceous
      shell (Arcella intermedia). All species but Difflugia oblonga branched within the
      recently erected suborder Sphaerothecina, confirming the synapomorphic value of
      an oviform or discoid shell. Thus, we propose that species with an oviform or
      discoid shell currently classified within genus Difflugia must be transferred to
      other genera, thus continuing the process of taxonomic revision of genus
      Difflugia, the largest Arcellinida genus. We therefore transferred the current
      and the previously sequenced oviform Difflugia spp. to Netzelia spp., based on
      the shared globular/oviform shell shape and their monophyly. Another species, D.
      labiosa, formed an independent lineage that branched as a sister clade to Arcella
      spp.; based on the shell morphology and their phylogenetic position, we
      considered D. labiosa as incertae sedis.

PMID- 28433923
TI  - UHPLC-Q-Orbitrap-HRMS-based global metabolomics reveal metabolome modifications
      in plasma of young women after cranberry juice consumption.
AB  - Plasma metabolome in young women following cranberry juice consumption were
      investigated using a global UHPLC-Q-Orbitrap-HRMS approach. Seventeen female
      college students, between 21 and 29 years old, were given either cranberry juice
      or apple juice for three days using a cross-over design. Plasma samples were
      collected before and after juice consumption. Plasma metabolomes were analyzed
      using UHPLC-Q-Orbitrap-HRMS followed by orthogonal partial least squares
      discriminant analyses (OPLS-DA). S-plot was used to identify discriminant
      metabolites. Validated OPLS-DA analyses showed that the plasma metabolome in
      young women, including both exogenous and endogenous metabolites, were altered
      following cranberry juice consumption. Cranberry juice caused increases of
      exogenous metabolites including quinic acid, vanilloloside, catechol sulfate, 3,4
      dihydroxyphenyl ethanol sulfate, coumaric acid sulfate, ferulic acid sulfate, 5
      (trihydroxphenyl)-gamma-valerolactone, 3-(hydroxyphenyl)proponic acid,
      hydroxyphenylacetic acid and trihydroxybenzoic acid. In addition, the plasma
      levels of endogenous metabolites including citramalic acid, aconitic acid,
      hydroxyoctadecanoic acid, hippuric acid, 2-hydroxyhippuric acid,
      vanilloylglycine, 4-acetamido-2-aminobutanoic acid, dihydroxyquinoline, and
      glycerol 3-phosphate were increased in women following cranberry juice
      consumption. The metabolic differences and discriminant metabolites observed in
      this study may serve as biomarkers of cranberry juice consumption and explain its
      health promoting properties in human.

PMID- 28433922
TI  - Effects of aging on prefrontal brain activation during challenging walking
      conditions.
AB  - BACKGROUND: Deficits in cognitive domains, in particular, those related to the
      prefrontal cortex, contribute to diminished walking performance in complex
      conditions in older age. Studies using functional near infra-red spectroscopy
      (fNIRS) reported inconsistent findings of brain activation age-related changes in
      response to increased task demands. We aimed to study the effects of aging on
      gait and prefrontal activation in complex walking tasks with internal and
      external task demands. METHODS: Twenty-three healthy young adults (30.9+/-3.7yrs)
      and 20 healthy older adults (69.7+/-5.8yrs) participated in this study. Gait and
      prefrontal activation were assessed during three walking conditions: (1) usual
      walking, (2) dual tasking (internal task demands) and, (3) obstacle negotiation
      (external task demands). fNIRS measured changes in oxygenated hemoglobin
      concentrations in the prefrontal cortex. RESULTS: Several gait measures were
      worse in older compared to younger adults under all walking conditions (p<0.005).
      Even at the lowest level of challenge, older adults had significant increases in
      HbO2 levels during usual walking, relative to standing (p=0.006). Both groups
      showed increased activation during dual-task (p<0.002) and during obstacle
      negotiation (p<0.003). CONCLUSIONS: Prefrontal activation during walking is
      dependent on age and task properties and that older adults apparently rely more
      on cognitive resources even during usual walking task.

PMID- 28433924
TI  - The metabolic fate of isotopically labeled trimethylamine-N-oxide (TMAO) in
      humans.
AB  - Trimethylamine-N-oxide (TMAO) is associated with chronic disease risk. However,
      little is known about the metabolic fate of dietary TMAO. This study sought to
      quantitatively elucidate the metabolic fate of orally consumed TMAO in humans. As
      part of a crossover feeding study, healthy young men (n=40) consumed 50-mg
      deuterium-labeled methyl d9-TMAO (d9-TMAO), and enrichments of TMAO and its
      derivatives were measured in blood for 6 h, urine and stool, as well as skeletal
      muscle in a subset of men (n=6). Plasma d9-TMAO was detected as early as 15 min,
      increased until 1 h and remained elevated through the 6-h period. TMAO exhibited
      an estimated turnover time of 5.3 h, and ~96% of the dose was eliminated in urine
      by 24 h, mainly as d9-TMAO. No d9-TMAO was detected in feces. Notably, d9-TMAO
      and d9-trimethylamine were detected in skeletal muscle (n=6) at 6 h, and the
      enrichment ratio of d9-TMAO to d9-trimethylamine was influenced by a genetic
      variant in flavin-containing monooxygenase isoform 3 (FMO3 G472A). These results
      suggest that the absorption of orally consumed TMAO is near complete and does not
      require processing by gut microbes. TMAO exhibits fast turnover in the
      circulation with the majority being eliminated in urine within 24 h. A small
      portion of the dose, however, is taken up by extrahepatic tissue in a manner that
      appears to be under the influence of FMO3 G472A polymorphism. This trial was
      registered at clinicaltrials.gov as NCT02558673.

PMID- 28433925
TI  - Low-dose pollutant mixture triggers metabolic disturbances in female mice leading
      to common and specific features as compared to a high-fat diet.
AB  - Environmental pollutants are potential etiologic factors of obesity and diabetes
      that reach epidemic proportions worldwide. However, it is important to determine
      if pollutants could exert metabolic defects without directly inducing obesity.
      The metabolic disturbances triggered in nonobese mice lifelong exposed to a
      mixture of low-dose pollutants (2,3,7,8-tetrachlorodibenzo-p-dioxine,
      polychlorinated biphenyl 153, diethylhexyl-phthalate, and bisphenol A) were
      compared with changes provoked by a high-fat high-sucrose (HFHS) diet not
      containing the pollutant mixture. Interestingly, females exposed to pollutants
      exhibited modifications in lipid homeostasis including a significant increase of
      hepatic triglycerides but also distinct features from those observed in diet
      induced obese mice. For example, they did not gain weight nor was glucose
      tolerance impacted. To get more insight, a transcriptomic analysis was performed
      in liver for comparison. We observed that in addition to the xenobiotic/drug
      metabolism pathway, analysis of the hepatic signature illustrated that the
      steroid/cholesterol, fatty acid/lipid and circadian clock metabolic pathways were
      targeted in response to pollutants as observed in the diet-induced obese mice.
      However, the specific sets of dysregulated annotated genes (>1300) did not
      overlap more than 40% between both challenges with some genes specifically
      altered only in response to pollutant exposure. Collectively, results show that
      pollutants and HFHS affect common metabolic pathways, but by different, albeit
      overlapping, mechanisms. This is highly relevant for understanding the
      synergistic effects between pollutants and the obesogenic diet reported in the
      literature.

PMID- 28433926
TI  - Discredited legacy: Stigma and familial amyloid polyneuropathy in Northwestern
      Portugal.
AB  - RATIONALE: Genetic inherited conditions may result in feelings of stigmatisation,
      mainly because of visible physical appearance and its transmissibility to
      offspring. OBJECTIVE: This article reports accounts of stigmatisation from
      Portuguese patients affected by the inherited neurodegenerative disease, familial
      amyloid polyneuropathy (FAP), living in the largest cluster of patients
      worldwide. METHOD: We draw on semi-structured interviews conducted with
      individuals at-risk or affected by FAP, recruited through the national patients'
      association, about their experiences of stigmatisation related to the illness.
      RESULTS: Findings highlight the influence of a discrediting social context in the
      enactment of stigma. FAP was described as a source of devaluation and social
      distance and was permeated by beliefs of contagion in the community, especially
      in the past. The multigenerational nature of the illness within small communities
      was felt as a source of rejection for courtship and of devalued reproductive
      worth. Decisions to have (potentially affected) children seemed to be a target of
      implicit negative judgment. Dealing with stigma entailed restraint in talking
      about FAP especially outside the family, resistance to being treated as
      different, and social withdrawal. Some participants referred to recent
      substantial improvements in their social acceptance and a reduction in the
      intensity of the stigmatisation to which they are subject. CONCLUSION: The
      pattern of stigma may have changed considerably within the past few decades, as
      medical information about the disease became more widespread, as new medications
      have been introduced and as clinical trials of other potential treatments have
      been established. Our findings report the social consequences of stigma towards
      this disease group and may help to understand how stigma is experienced in other
      heritable diseases.

PMID- 28433927
TI  - Performing boundary work: The emergence of a new practice in a hybrid operating
      room.
AB  - This paper addresses the processes of boundary work, in relation to the
      introduction of new technology, unfolding during the emergence of new medical
      practices. Inspired by Gieryn's fluid and practical view of boundaries and
      boundary work, and by Actor-Network Theory's description of scripting processes,
      we study the processes of negotiating and (re-)constructing boundaries in order
      to reveal both the interactions between different kinds of boundary work and
      their situatedness in the context of the emerging practice. We conducted a
      longitudinal and qualitative study of a generic Hybrid Operating Room at a
      Swedish university hospital, where sophisticated imaging devices are combined
      with open surgery procedures in a single room; consequently, medical requirements
      regarding radiology, surgery and anesthesia, as well as the specificities of the
      new technology, all need to be met at the same time. The study shows how the
      visibility of boundaries is a result of as well as a condition for boundary work,
      how boundary work is a dynamic and iterative process, and how it unfolds in a
      recursive relationship between practice and boundaries.

PMID- 28433928
TI  - Child disability and siblings' healthcare expenditures in a context of child
      fostering.
AB  - Many studies have assessed the impact of disability on healthcare expenditures
      for the disabled child, but practically none has considered the externalities of
      a child's disability in terms of healthcare expenditures for his/her siblings.
      This study therefore seeks to measure the impact of a child's disability on the
      allocation of healthcare expenditures among children of a household. It uses data
      from the 2011 Demographic Health and Multiple Indicator Cluster Survey (DHS-MICS)
      conducted in Cameroon by the National Statistics Institute (INS), with support
      from UNFPA, UNICEF, the World Bank and USAID. The disability module of the survey
      was administered to 17,864 children under age 18. Multivariate analyses (two-part
      model with logistic then GLM regression) showed that a disability significantly
      increases the monthly healthcare expenditures for the disabled child by XAF 204.
      This effect does not differ significantly whether or not the disabled child is
      fostered (does not live with his/her mother). Living with a disabled child has no
      impact on healthcare expenditures of a child. However, if the child is a true
      sibling (same mother), having a disabled sibling reduces the healthcare
      expenditures allocated to that child by XAF 102. Childhood disability therefore
      has a potentially wider effect on the health of siblings.

PMID- 28433929
TI  - Pollution characteristics and human health risks of potentially (eco)toxic
      elements (PTEs) in road dust from metropolitan area of Hefei, China.
AB  - This study aims to investigate the pollution characteristics of road dust and
      their associated health risks of potentially toxic elements (PTEs) to humans
      using array-based risk assessment models described by United States Environmental
      Protection Agency (USEPA) in a metropolitan area of Hefei, China. Geoaccumulation
      index (Igeo) was used to describe pollution characteristics of roadside dust in
      urban, periurban and industrial areas. Results indicate that industrial roadside
      dust was contaminated with Fe, Ni, Cu, Ti, V, Pb, Ba, Sb, Cr, Sn, Pb, As and Ga
      showing Igeo value (log2 (x)) between Igeo class 3 to 4. In other hand, urban
      roadside dust contamination with Cu, Zn, Sb and Ga ranged between Igeo classes 2
      to 3 and with As and Pb ranged between Igeo classes 4 to 5. Furthermore, health
      risk assessment revealed negligible non-cancerous health hazard in all sites
      including urban, periurban and industrial areas. The hazard quotient (HQ) and
      hazard Index (HI) values for all exposure routes (ingestion, inhalation, and
      dermal contact) were <1 except for chromium with HI value of 1.06E+00 in
      industrial areas. Moreover, the most prominent exposure route was ingestion
      (HQing) and the non-carcinogenic health risks were found to be high in case of
      children compared to the adults. The cancer risk from As, Co, Cr, Ni, and Pb was
      found to be in safe levels as the RI (carcinogenic risks) values were below the
      limits for carcinogens (1.00E-6 to 1.00E-4).

PMID- 28433930
TI  - Environmental Electrokinetics for a sustainable subsurface.
AB  - Soil and groundwater are key components in the sustainable management of the
      subsurface environment. Source contamination is one of its main threats and is
      commonly addressed using established remediation techniques such as in-situ
      chemical oxidation (ISCO), in-situ chemical reduction (ISCR; most notably using
      zero-valent iron [ZVI]), enhanced in-situ bioremediation (EISB),
      phytoremediation, soil-washing, pump-and-treat, soil vapour extraction (SVE),
      thermal treatment, and excavation and disposal. Decades of field applications
      have shown that these techniques can successfully treat or control contaminants
      in higher permeability subsurface materials such as sands, but achieve only
      limited success at sites where low permeability soils, such as silts and clays,
      prevail. Electrokinetics (EK), a soil remediation technique mostly recognized in
      in-situ treatment of low permeability soils, has, for the last decade, been
      combined with more conventional techniques and can significantly enhance the
      performance of several of these remediation technologies, including ISCO, ISCR,
      EISB and phytoremediation. Herein, we discuss the use of emerging EK techniques
      in tandem with conventional remediation techniques, to achieve improved
      remediation performance. Furthermore, we highlight new EK applications that may
      come to play a role in the sustainable treatment of the contaminated subsurface.

PMID- 28433931
TI  - Alkaline-earth elements of scalp hair and presence of hypertension in housewives:
      A perspective of chronic effect.
AB  - The relationship between population intakes of alkaline-earth elements (AEEs) and
      hypertension risk remains under discussion. Hair AEE concentrations can indicate
      their intake levels into human body. Thus, we aimed to investigate an association
      of hair AEE concentrations with hypertension risk, and the potential effect of
      dietary habit on this association. We recruited 398 housewives [163 subjects with
      hypertension (case group) and 235 subjects without hypertension (control group)]
      in Shanxi Province of north China. The scalp hair grown in the recent 2 years of
      each subject was collected and analyzed for the four concerned AEEs [i.e. calcium
      (Ca), magnesium (Mg), strontium (Sr), and barium (Ba)]. Our study results
      revealed that median concentrations (MUg/g hair) of hair AEEs in the case group
      were systematically lower than those in control group [i.e. 701 vs. 1271 of Ca,
      55.2 vs. 88.3 of Mg, 4.60 vs. 10.4 of Sr, and 1.02 vs. 1.68 of Ba]. Lower levels
      of the four individual AEEs of hair were associated with an increased presence of
      hypertension, respectively. Moreover, hair AEE concentrations were all positively
      correlated with the ingestion frequencies of meat, eggs, fresh vegetables, and
      fruits, while negatively with that of salted vegetables. A high ingestion
      frequency of fresh vegetables was associated with a lower prevalence of
      hypertension with or without adjusting confounders, while salted vegetables
      revealed a reverse tend. It was concluded that low hair AEEs, as markers of their
      long-term dietary intake, were associated with the presence of hypertension in a
      rural Chinese women.

PMID- 28433932
TI  - The unseen rhizosphere root-soil-microbe interactions for crop production.
AB  - The underground root-soil-microbe interactions are extremely complex, but vitally
      important for aboveground plant growth, health and fitness. The pressure to
      reduce our reliance on agrochemicals, and sustainable efforts to develop
      agriculture makes rhizosphere interactions' research a hotspot. Recent advances
      provide new insights about the signals, pathways, functions and mechanisms of
      these interactions. In this review, we provide an overview about recent progress
      in rhizosphere interaction networks in crops. We also discuss a holistic view of
      the root-soil-rhizomicrobiome interactions achieved through the advances of omics
      and bioinformatics technologies, and the potential strategies to manage the
      complex rhizosphere interactions for enhancing crop production.

PMID- 28433933
TI  - Functional foods in pet nutrition: Focus on dogs and cats.
AB  - Functional foods provide health benefits if they are consumed on a regular basis
      as part of a varied diet. In this review, we discuss the availability and role of
      functional foods in pet nutrition with a focus on dogs and cats. Indeed,
      functional foods modify gastrointestinal physiology, promote changes in
      biochemical parameters, improve brain functions and may reduce or minimize the
      risk of developing specific pathologies. This evidence derives largely from
      clinical studies while only limited evidence is available from studies in dogs
      and cats. Therefore, functional food consumption should be further investigated
      in pet nutrition to understand how dietary interventions can be used for disease
      prevention and treatment.

PMID- 28433934
TI  - Amino acid functionalized gadofullerene nanoparticles with superior antitumor
      activity via destruction of tumor vasculature in vivo.
AB  - Researchers have been puzzled of the therapy of malignant tumors and the current
      therapeutic strategies are always accompanied by toxicity or side effects.
      Developing efficient nanodrugs could reduce the dosage and greatly improve the
      therapeutic effects in cancer treatments. Here we initially reported a novel kind
      of gadofullerene nanoparticles functionalized with amino acid (beta-alanine),
      which exhibited a superior antitumor activity in hepatoma H22 models via a novel
      therapeutic mechanism. The involvement of beta-alanine improved the tumor
      inhibition rate up to 76.85% for a single treatment by strengthening the
      interaction with radiofrequency (RF) and extending blood circulation time. It
      realized a highly antivascular treatment to cut off the nutrient supply of tumor
      cells by physically destroying the abnormal tumor blood vessels assisted by RF.
      In situ and real-time observation of the vascular change was conducted using the
      dorsal skin fold chamber model, which corresponded to the erythrocyte diapedesis
      in histopathological examination. The ultrastructural changes of vascular
      endothelial cells were further investigated by environmental scanning electron
      microscopy and transmission electron microscopy. Long-term toxicity evaluation
      showed that the GF-Ala nanoparticles could be eliminated from the mice after
      several days and no obvious toxicity was found to the main organs. All these
      encouraging results suggest GF-Ala nanoparticles are valuable for the significant
      therapeutic potential with high-efficacy and low-toxicity.

PMID- 28433936
TI  - Sustained viral gene delivery from a micro-fibrous, elastomeric cardiac patch to
      the ischemic rat heart.
AB  - Biodegradable and elastomeric patches have been applied to the surface of
      infarcted hearts as temporary mechanical supports to effectively alter adverse
      left ventricular remodeling processes. In this report, recombinant adeno
      associated virus (AAV), known for its persistent transgene expression and low
      pathogenicity, was incorporated into elastomeric polyester urethane urea (PEUU)
      and polyester ether urethane urea (PEEUU) and processed by electrospinning into
      two formats (solid fibers and core-sheath fibers) designed to influence the
      controlled release behavior. The extended release of AAV encoding green
      fluorescent protein (GFP) was assessed in vitro. Sustained and localized viral
      particle delivery was achieved over 2 months in vitro. The biodegradable cardiac
      patches with or without AAV-GFP were implanted over rat left ventricular lesions
      three days following myocardial infarction to evaluate the transduction effect of
      released viral vectors. AAV particles were directly injected into the infarcted
      hearts as a control. Cardiac function and remodeling were significantly improved
      for 12 weeks after patch implantation compared to AAV injection. More GFP genes
      was expressed in the AAV patch group than AAV injection group, with both alpha
      SMA positive cells and cardiac troponin T positive cells transduced in the patch
      group. Overall, the extended release behavior, prolonged transgene expression,
      and elastomeric mechanical properties make the AAV-loaded scaffold an attractive
      option for cardiac tissue engineering where both gene delivery and appropriate
      mechanical support are desired.

PMID- 28433935
TI  - Distinct ON/OFF fluorescence signals from dual-responsive activatable nanoprobes
      allows detection of inflammation with improved contrast.
AB  - Visualization of biochemical changes associated with disease is of great clinical
      significance, as it should allow earlier, more accurate diagnosis than structural
      imaging, facilitating timely clinical intervention. Herein, we report combining
      stimuli-responsive polymers and near-infrared fluorescent dyes (emission max: 790
      nm) to create robust activatable fluorescent nanoprobes capable of simultaneously
      detecting acidosis and oxidative stress associated with inflammatory
      microenvironments. The spectrally-resolved mechanism of fluorescence activation
      allows removal of unwanted background signal (up to 20-fold reduction) and
      isolation of a pure activated signal, which enables sensitive and unambiguous
      localization of inflamed areas; target-to-background ratios reach 22 as early as
      3 h post-injection. This new detection platform could have significant clinical
      impact in early detection of pathologies, individual tailoring of drug therapy,
      and image-guided tumor resection.

PMID- 28433937
TI  - Perturbation effect of reduced graphene oxide quantum dots (rGOQDs) on aryl
      hydrocarbon receptor (AhR) pathway in zebrafish.
AB  - Graphene quantum dots (GQDs) has been widely used in enormous fields, however,
      the inherent molecular mechanism of GQDs for potential risks in biological system
      is still elusive to date. In this study, the outstanding reduced graphene quantum
      dots (rGOQDs) with the QY as high as 24.62% were successfully synthesized by the
      improved Hummers method and DMF hydrothermal treatment approach. The rGOQDs were
      N-doped photoluminescent nanomaterials with functional groups on the surface. The
      fluorescent bio-imaging was performed by exposing zebrafish in different
      concentrations of the as-prepared rGOQDs, and the distribution of rGOQDs was
      successfully observed. Moreover, the developmental toxicity and genotoxicity were
      evaluated to further investigate the potential hazard of rGOQDs. The result
      indicated that rGOQDs were responsible for the dose-dependent abnormalities on
      the development of zebrafish. Since the real-time polymerase chain reaction (RT
      PCR) results showed that the expression of cyp1a was the highest expression in
      the selected genes and significantly up-regulated 8.49 fold in zebrafish, the
      perturbation of rGOQDs on aryl hydrocarbon receptor (AhR) pathway was
      investigated by using the Tg(cyp1a:gfp) zebrafish for the first time. The results
      demonstrated that rGOQDs significantly increased the green fluorescent protein
      (GFP) expression promoted by cyp1a in a dose-dependent manner, which was also
      further confirmed by the western blotting. This study offered an opportunity to
      reveal the potential hazards of in vivo bio-probes, which provided a valuable
      reference for investigating the graphene-based materials on the disturbance of
      AhR pathway in biological organisms.

PMID- 28433938
TI  - Imaging lysosomal highly reactive oxygen species and lighting up cancer cells and
      tumors enabled by a Si-rhodamine-based near-infrared fluorescent probe.
AB  - Lysosomes have recently been regarded as the attractive pharmacological targets
      for selectively killing of cancer cells via lysosomal cell death (LCD) pathway
      that is closely associated with reactive oxygen species (ROS). However, the
      details on the ROS-induced LCD of cancer cells are still poorly understood,
      partially due to the absence of a lysosome-targetable, robust, and biocompatible
      imaging tool for ROS. In this work, we brought forward a Si-rhodamine-based
      fluorescent probe, named PSiR, which could selectively and sensitively image the
      pathologically more relavent highly reactive oxygen species (hROS: HClO, HO, and
      ONOO-) in lysosomes of cancer cells. Compared with many of the existing hROS
      fluorescent probes, its superiorities are mainly embodied in the high stability
      against autoxidation and photoxidation, near-infrared exitation and emission,
      fast fluorescence off-on response, and specific lysosomal localization. Its
      practicality has been demonstrated by the real-time imaging of hROS generation in
      lysosomes of human non-small-cell lung cancer cells stimulated by anticancer drug
      beta-lapachone. Moreover, the probe was sensitive enough for basal hROS in cancer
      cells, allowing its further imaging applications to discriminate not only cancer
      cells from normal cells, but also tumors from healthy tissues. Overall, our
      results strongly indicated that PSiR is a very promising imaging tool for the
      studies of ROS-related LCD of cancer cells, screening of new anticancer drugs,
      and early diagnosis of cancers.

PMID- 28433939
TI  - Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes
      stimulated by a nitric oxide releasing polymer.
AB  - Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new
      candidates for the treatment of degenerative diseases or injury and may provide
      an alternative to cell-based therapy. However, the compositions in MSC-derived
      exosomes are highly influenced by the microenvironment in which their original
      cells reside. Here, we hypothesized that a nitric oxide (NO)-releasing polymer
      can boost the proangiogenic compositions of exosomes and enhance their
      proangiogenic capacity. Our results demonstrated that exosomes, released from
      human placenta-derived MSCs (hP-MSCs) by NO stimulation, augment the angiogenic
      effects of human umbilical vein endothelial cells (HUVECs) in vitro. Moreover,
      exosomes released from hP-MSCs by NO stimulation revealed superior angiogenic
      effects and ameliorated limb function in a murine model of hind limb ischemia.
      Further analysis demonstrated that increased VEGF and miR-126 levels in exosomes
      released from hP-MSCs by NO stimulation were identified as a novel mechanism
      contributing to the increased capacity of these exosomes to promote angiogenic
      processes. In conclusion, designing specific microenvironments for in vitro stem
      cell culture, such as those containing bioactive material, will facilitate the
      development of customized exosomes encapsulating a beneficial composition of stem
      cells for cell-free therapeutic applications.

PMID- 28433940
TI  - A novel dual-ratiometric-response fluorescent probe for SO2/ClO- detection in
      cells and in vivo and its application in exploring the dichotomous role of SO2
      under the ClO- induced oxidative stress.
AB  - Intracellular reactive sulfur species and reactive oxygen species play vital
      roles in immunologic mechanism. As an emerging signal transmitter, SO2 can be
      generated as the anti-oxidant, while SO2 is also a potential oxidative stress
      inducer in organism. Aiming to elucidate in-depth the dichotomous role of SO2
      under oxidative stress, we designed a dual-response fluorescent probe that
      enabled the respective or successive detection of SO2 and ClO-. The probe itself
      emits the red fluorescence (625 nm) which can largely switch to blue (410 nm) and
      green fluorescence (500 nm) respectively in response to SO2 and ClO-, allowing
      the highly selective and accurate ratiometric quantification for both SO2 and ClO
      in cells. Moreover the ultrafast (SO2: <60 s; ClO-: within sec) and highly
      sensitive (detection limits: SO2: 3.5 nM; ClO-: 12.5 nM) detection were achieved.
      With the robust applicability, the developed probe was successfully used to
      quantify SO2 and endogenous ClO- in respectively the HeLa cells and the RAW 264.7
      cells, as well as to visualize the dynamic of SO2/ClO- in zebrafish. The
      fluorescent imaging studies and flow cytometry analysis confirmed the burst-and
      depletion and meanwhile the oxidative-and-antioxidative effects of intracellular
      SO2 under the NaClO induced oxidative stress.

PMID- 28433941
TI  - Self assembled dual responsive micelles stabilized with protein for co-delivery
      of drug and siRNA in cancer therapy.
AB  - Design of safe and efficient vehicles for the combinatorial delivery of drugs and
      genetic agents is an emerging requisite for achieving enhanced therapeutic effect
      in cancer. Even though several nanoplatforms have been explored for the co
      delivery of drugs and genetic materials the translation of these systems to
      clinical phase is still a challenge, mainly due to tedious synthesis procedures,
      lack of serum stability, inefficient scalability etc. Here in, we report
      development of reduction and pH sensitive polymeric graft of low molecular weight
      poly (styrene -alt -maleic anhydride) and evaluation of its efficacy in co
      delivering drug and siRNA. The polymer was modified with suitable components,
      which could help in overcoming various systemic and cellular barriers for
      successful co-delivery of drugs and nucleic acids to cancer cells, using simple
      chemical reactions. The polymeric derivative could easily self assemble in water
      to form smooth, spherical micellar structures, indicating their scalability.
      Doxorubicin and PLK-1 siRNA were selected as model drug and nucleic acid,
      respectively. Doxorubicin could be loaded in the self assembling micelles with an
      optimum loading content of ~8.6% w/w and efficient siRNA complexation was
      achieved with polymer/siRNA weight ratios >40. The polyplexes were stabilized in
      physiological saline by coating with bovine serum albumin (BSA). Stable drug
      loaded nanoplexes, for clinical administration, could be easily formulated by
      gently dispersing them in physiological saline containing appropriate amount of
      albumin. Drug release from the nanoplexes was significantly enhanced at low pH
      (5) and in the presence of 10 mM glutathione (GSH) showing their dual stimuli
      sensitive nature. In vitro cell proliferation assay and in vivo tumor regression
      study have shown synergistic effect of the drug loaded nanoplexes in inhibiting
      cancer cell proliferation. Facile synthesis steps, scalability and ease of
      formulation depict excellent clinical translation potential of the proposed
      nanosystem.

PMID- 28433942
TI  - Synthesis and characterization of poly(propylene imine)-dendrimer-grafted gold
      nanoparticles as nanocarriers of doxorubicin.
AB  - The aim of current work is synthesis 4th-generation-poly(propylene imine) (PPI)
      dendrimer modified gold nanoparticles (Au-G4A) as nanocarriers for doxorubicin
      (DOX) and studying in vitro drug release kinetics from nanocarriers into
      different media. Accordingly, AuNPs were synthesized by reduction of chloroauric
      acid (HAuCl4) aqueous solution with trisodium citrate and modified with
      cysteamine to obtain amine-functionalized (Au-NH2) nanoparticles. Au-NH2
      nanoparticles were used as multifunctional cores and participated in Michael
      addition of acrylonitrile and reduction process by lithium aluminum hydride (LAH)
      to synthesize Au-G4A nanoparticles. Also, peripheral primary amine groups of Au
      G4A were conjugated with folic acid (FA) (Au-G4F) to study the bioconjugation
      effect on drug release behavior of nanostructures. Ultraviolet spectroscopy (UV
      vis), atomic force microscopy (AFM), transmission electron microscopy (TEM),
      Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis
      (TGA) were used to approve the synthesis of different nanostructures. Finally, Au
      G4A and Au-G4F samples were loaded with DOX and exposed to environments with
      different pH values to examine the release properties of nanostructures. Also,
      drug release kinetics was investigated by fitting of experimental data with
      different release models. As a result, synthesized dendritic structures showed
      Higuchi and Korsmeyer-Peppas models release behavior due to better solubility of
      drug in release media with respect to dendrimer cavities and drug release through
      polymeric matrix respectively.

PMID- 28433943
TI  - Acute lung injury leads to depression-like symptoms through upregulation of
      neutrophilic and neuronal NADPH oxidase signaling in a murine model.
AB  - There is an increased prevalence of comorbid major depressive disorders with a
      number of inflammatory conditions which is thought to result from activation of
      the immune system. Acute lung injury (ALI) in humans has been also shown to be
      associated with depression previously. However, no study has explored the
      mechanism behind ALI-induced depression. NADPH oxidase (NOX-2) derived reactive
      oxygen species (ROS) are associated with neuropsychiatric disorders including
      depression. ROS generation via NOX-2 is also shown to be involved in the
      pathogenesis of ALI. Therefore, we hypothesized that ROS generation may be a
      common link between ALI and depression. The present study utilized LPS model of
      ALI in mice to explore the effect of lung inflammation on depression-like
      behavior and further delineate the role of NOX-2 signaling in it. ALI led to
      enhanced NOX-2 activation in neutrophils/brain and neuronal oxidative stress
      which was concurrent with depression-like symptoms as assessed by sucrose
      preference and tail suspension test. Role of neutrophilic NOX-2 in ALI-induced
      depression was confirmed by depletion of neutrophils as well NOX-2 inhibitor,
      apocynin. Both of these approaches led to reduction in depressive symptoms
      induced by ALI. The present study suggests that ALI-induced upregulation of
      neutrophilic NOX-2/ROS may contribute to depression-like symptoms in mice.

PMID- 28433944
TI  - Evaluation of vaccinal effectiveness of preparations containing membrane antigens
      of Leishmania (L.) amazonensis in experimental cutaneous leishmaniasis model.
AB  - American tegumentary leishmaniasis (ATL) is considered a neglected disease, for
      which an effective vaccine or an efficient diagnosis is not yet available and
      whose chemotherapeutic arsenal is threatened by the emergence of resistance by
      etiological agents such as Leishmania amazonensis. ATL is endemic in poor
      countries and has a high incidence in Brazil. Vaccines developed from native
      parasite fractions have led to the identification of defined antigenic subunits
      and the development of vaccine adjuvant technology. The purpose of the present
      study was to develop and compare preparations based on membrane antigens from L.
      amazonensis, as a biotechnological prototype for the immunoprophylaxis of the
      disease in a murine experimental model. For this purpose, batches of
      biodegradable polymeric micro/nanoparticles were produced, characterized and
      compared with other parasite's antigens in solution. All preparations containing
      membrane antigens presented low toxicity on murine macrophages. The in vivo
      evaluation of immunization efficacy was performed against a challenge with L.
      amazonensis, along with an evaluation of the immune response profile generated in
      BALB/C mice. The animals were followed for sample processing and quantification
      of serum-specific cytokines, nitrites and antibodies. The sera of animals
      immunized with the non-encapsulated antigen formulations showed higher
      intensities of nitrites and total IgGs. This approach evidenced the importance of
      the biological studies involving the immune response of the host against the
      parasite being interconnected and related to the subfractionation of its proteins
      in the search for more effective vaccine candidates.

PMID- 28433945
TI  - CQMUH-011, a novel adamantane sulfonamide compound, inhibits lipopolysaccharide-
      and D-galactosamine-induced fulminant hepatic failure in mice.
AB  - CQMUH-011, a novel adamantane sulfonamide compound, was shown to suppress
      macrophage activation and proliferation in our previous study. However, it is
      unknown whether CQMUH-011 has anti-inflammatory and hepatoprotective properties.
      In this study, we investigated the potential effects and mechanisms of CQMUH-011
      on lipopolysaccharide (LPS)-induced RAW264.7 cell activation in vitro and LPS-
      and D-galactosamine (D-GalN)-induced fulminant hepatic failure (FHF) in vivo. The
      results showed that in RAW264.7 cells challenged by LPS, CQMUH-011 inhibited cell
      proliferation and induced cell cycle arrest and apoptosis. Furthermore, CQMUH-011
      reduced tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta production
      and down-regulated the overexpression of toll-like receptor 4 (TLR4) and nuclear
      factor (NF)-kappaB induced by LPS in RAW264.7 cells. In vivo, CQMUH-011 reduced
      serum levels of aspartic aminotransferase and alanine transaminase and improved
      the mortality and hepatic pathological damage induced by LPS/D-GalN in mice.
      Moreover, CQMUH-011 significantly inhibited the serum levels of proinflammatory
      mediators, including TNF-alpha, IL-6, IL-1beta, nitric oxide (NO), and
      prostaglandin E2 (PGE2), and down-regulated the protein expression of TLR4, p38
      mitogen-activated protein kinases, NF-kappaB, NF-kappaB inhibitor alpha
      (IkappaBalpha), IkappaB kinase beta (IKKbeta), cyclooxygenase-2 (COX-2) and
      inducible NO synthases (iNOS) induced by LPS/D-GalN in mice. In conclusion, these
      results demonstrated that CQMUH-011 has a notable anti-inflammatory effect and
      protects mice from LPS/D-GalN-induced FHF and that the molecular mechanisms might
      be related to the inhibition of the TLR4/NF-kappaB signaling pathway activation,
      the subsequent decrease in proinflammatory mediator production, and the
      inhibition of macrophage activation.

PMID- 28433946
TI  - The activities of the E3 ubiquitin ligase COP1/SPA, a key repressor in light
      signaling.
AB  - Light is a critical signal to integrate plant growth and development with the
      environment. Downstream of photoreceptors, the E3 ubiquitin ligase COP1/SPA is a
      key repressor of photomorphogenesis which targets many positive regulators of
      light signaling, mainly transcription factors, for degradation in darkness. In
      light-grown plants COP1/SPA activity is repressed, allowing light responses to
      occur. This review provides an overview on our current knowledge on COP1/SPA
      repressor function, focusing in particular on the roles of the respective protein
      domains and the mechanisms of light-induced inactivation of COP1/SPA. Moreover,
      we summarize how COP1 activity is regulated by other interacting proteins, such
      as a SUMO E3 ligase and Phytochrome-Interacting Factors (PIFs), as well as by
      hormones. At last, several novel functions of COP1 that were recently revealed
      are included.

PMID- 28433947
TI  - Maximum likelihood estimation of cardiac fiber bundle orientation from
      arbitrarily spaced diffusion weighted images.
AB  - We propose an estimation scheme for local fiber bundle direction in the left
      ventricle directly from gray values of arbitrarily spaced cardiac diffusion
      weighted images (DWI). The approach is based on a parametric and space-dependent
      mathematical representation of the myocardial fiber bundle orientation and hence
      the diffusion tensor (DT) for the ventricular geometry. By solving a nonlinear
      inverse problem derived from a maximum likelihood estimator, the degrees of
      freedom of the fiber and DT model can be estimated from the measured gray values
      of the DWIs. The continuity of the DT model allows to relax the restriction to
      the individual DWIs to match spatially like for voxelwise DT calculation. Hence,
      the spatial misalignment between image slices with different diffusion encoding
      directions, that is encountered in-vivo cardiac imaging practice can be
      integrated into the estimation scheme. This feature results then in a negligible
      impact of the spatial misalignment on the reconstructed solution. We illustrate
      the methodology using synthetic data and compare it against a previously reported
      fiber bundle reconstruction technique. To show the potential for real data, we
      also present results for multi-slice data constructed from ex-vivo cardiac
      diffusion weighted measurements in both mono- and bi-ventricular configurations.

PMID- 28433948
TI  - Metabolic syndrome in subjects with bipolar disorder and major depressive
      disorder in a current depressive episode: Population-based study: Metabolic
      syndrome in current depressive episode.
AB  - OBJECTIVE: To assess the differences in the prevalence of the metabolic syndrome
      (MetS) and their components in young adults with bipolar disorder (BD) and major
      depressive disorder (MDD) in a current depressive episode. METHODS: This was a
      cross-sectional study with young adults aged 24-30 years old. Depressive episode
      (bipolar or unipolar) was assessed using the Mini International Neuropsychiatric
      Interview - Plus version (MINI Plus). The MetS was assessed using the National
      Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). RESULTS:
      The sample included 972 subjects with a mean age of 25.81 (+/-2.17) years. Both
      BD and MDD patients showed higher prevalence of MetS compared to the population
      sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of
      glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of
      HDL cholesterol, and a higher prevalence of abdominal obesity were observed in
      both BD and MDD individuals with current depressive episode compared to the
      general population. Moreover, there was a significant difference on BMI values in
      the case of BD and MDD subjects (p = 0.016). CONCLUSION: Metabolic components
      were significantly associated with the presence of depressive symptoms,
      independently of the diagnosis.

PMID- 28433949
TI  - The dimensional structure of psychopathology in 22q11.2 Deletion Syndrome.
AB  - BACKGROUND: 22q11.2 Deletion Syndrome (22q11.2DS) is one of the strongest known
      genetic risk factors for developing schizophrenia. Individuals with 22q11.2DS
      have high rates of neurodevelopmental disorders in childhood, while in adulthood
      ~25% develop schizophrenia. Similar to the general population, high rates of
      comorbidity are common in 22q11.2DS. Employing a dimensional approach where
      psychopathology is examined at the symptom-level as complementary to diagnostic
      categories in a population at such high genetic risk for schizophrenia can help
      gain a better understanding of how psychopathology is structured as well as its
      genetic underpinnings. This is the first study to examine the dimensional
      structure of a wide spectrum of psychopathology in the context of a homogeneous
      genetic etiology like 22q11.2DS. METHODS: We evaluated 331 individuals with
      22q11.2DS, mean age (SD) = 16.9(8.7); 51% males, who underwent prospective
      comprehensive phenotyping. We sought to replicate previous findings by examining
      a bi-factor model that derives a general factor of psychopathology in addition to
      more specific dimensions of psychopathology (i.e., internalizing, externalizing
      and thought disorder). RESULTS: Psychopathology in 22q11.2DS was divided into one
      'general psychopathology' factor and four specific dimensions (i.e., 'anxiety',
      'mood', 'ADHD' and 'psychosis'). The 'psychosis' symptoms loaded strongly on the
      'general psychopathology' factor. CONCLUSIONS: The similarity of the symptom
      structure of psychopathology between 22q11.2DS and community and clinical
      populations without the deletion indicate that 22q11.2DS can provide a model to
      explore alternative approaches to our current nosology. Our findings add to a
      growing literature indicating the need to reorganize current diagnostic
      classification systems.

PMID- 28433950
TI  - An electrocortical investigation of emotional face processing in military-related
      posttraumatic stress disorder.
AB  - PTSD is a disorder of emotion dysregulation. Although much work has intended to
      elucidate the neural underpinnings of the disorder, much remains unknown about
      the neurobiological substrates of emotion dysregulation in PTSD. In order to
      assess the relationship between a neural measure of attention to emotion (i.e.
      the late positive potential; LPP) and PTSD symptoms, EEG was recorded and
      examined as a potential predictor of military-related PTSD symptoms in a sample
      of 73 OEF/OIF/OND veterans. Results revealed that higher PTSD symptoms were
      related to an attenuated LPP response to angry facial expressions. This finding
      was not observed for happy or fearful faces. The current study provides initial
      evidence that, in a relatively young, mostly male sample of OEF/OIF/OND veterans,
      hyporeactivity to angry faces at the neural level may provide phenotypic data to
      characterize individual differences in PTSD symptom severity. This work may
      assist in future studies that seek to examine useful psychophysiologic targets
      for treatment and early interventions.

PMID- 28433951
TI  - Transesophageal echocardiography in the evaluation of the trauma patient: A
      trauma resuscitation transesophageal echocardiography exam.
AB  - The point-of-care ultrasound exam has become an essential tool for hemodynamic
      monitoring and resuscitation in the trauma bay as well as the intensive care
      unit. Transthoracic ultrasound provides a dynamic assessment of cardiac function,
      volume status, and fluid responsiveness that offers potential advantage over
      traditional methods of hemodynamic monitoring. More recently, a focused
      transthoracic echocardiography exam was described to improve immediate
      resuscitation of severely injured patients in the trauma bay. Transesophageal
      echocardiography (TEE) for trauma could expand upon the role of focused
      echocardiography. TEE offers improved visualization of cardiac anatomy and
      physiology, improved diagnostic accuracy, and real-time assessment of
      intraoperative resuscitation progress, particularly in the operating room. This
      review discusses the fundamental principles of echocardiography as well as
      different ultrasound modes with their respective strengths and limitations. It
      reviews the current literature on the use of TEE in trauma, and suggests views
      for a trauma resuscitation transesophageal echocardiography exam (TREE),
      including sample images and videos.

PMID- 28433952
TI  - What chickens might tell us about the MHC class II system.
AB  - Almost all knowledge about the structure and function of MHC class II molecules
      outside of mammals comes from work with chickens. Most of the genes implicated in
      the class II system are present in chickens, so it is likely that the machinery
      of antigen processing and peptide-loading is similar to mammals. However, there
      is only one isotype (lineage) of classical class II genes, with one monomorphic
      DR-like BLA gene and two polymorphic BLB genes, located near one DMA and two DMB
      genes. The DMB2 and BLB2 genes are widely expressed at high levels, whereas the
      DMB1 and BLB1 genes are only expressed at highest levels in spleen and intestine,
      suggesting the possibility of two class II systems in chickens.

PMID- 28433953
TI  - The ability of early serial developmental assessment to predict outcome at 5years
      following neonatal hypoxic-ischaemic encephalopathy.
AB  - BACKGROUND: Neurodevelopmental difficulties in children following hypoxic
      ischaemic encephalopathy (HIE) may not emerge until school age. AIMS: To evaluate
      the value and stability of early serial developmental assessments in predicting
      long-term outcome. STUDY DESIGN: Prospective study of infants with neonatal HIE
      and early continuous EEG at birth. SUBJECTS: Term infants with HIE were recruited
      at birth. Development was measured at 6, 12 and 24months using the Revised
      Griffiths' Scales (GMDS-R). OUTCOME MEASURES: Intellectual abilities at age five
      were measured using the Wechsler Preschool & Primary Scale of Intelligence (WPPSI
      IIIUK) and the 'numbers' subtest from the Children's Memory Scale. Overall five
      year outcome was also reported. RESULTS: IQ outcome was available in forty-seven
      surviving children (28 male, 19 female: mean (SD) age 64.0(5.7) months. Mean
      processing speed (p=0.01) and short-term verbal memory (p=0.005) were below the
      norm. Global development (GDQ) at 6, 12 and 24months correlated (p<0.01) with
      five-year global, verbal and performance IQ with improved correlation over time.
      Normal GDQ throughout early childhood predicted normal IQ at 5years (24month
      AUROC value=0.941, p=0.001). An abnormal early GDQ score at any stage in the
      first 24months had excellent negative predictive values, superior to those for
      neonatal Sarnat and EEG grading. CONCLUSIONS: Normal early development predicts
      normal 5year IQ with prediction increasing over time. Repeated measurement is
      warranted due to instability of findings across the first two years. Follow-up
      for children with abnormal early development is warranted given high sensitivity
      for school-age global abnormal outcome.

PMID- 28433954
TI  - Lipidomic profile in three species of dinoflagellates (Amphidinium carterae,
      Cystodinium sp., and Peridinium aciculiferum) containing very long chain
      polyunsaturated fatty acids.
AB  - This study describes the identification of very long chain polyunsaturated fatty
      acids (VLCPUFAs) in three strains of dinoflagellates (Amphidinium carterae,
      Cystodinium sp., and Peridinium aciculiferum). The strains were cultivated and
      their lipidomic profiles were obtained by high resolution mass spectrometry with
      the aid of positive and negative electrospray ionization (ESI) mode by Orbitrap
      apparatus. Hydrophilic interaction liquid chromatography (HILIC/ESI) was used to
      separate major lipid classes of the three genera of dinoflagellates by neutral
      loss scan showing the ion [M + H-28:8]+, where 28:8 was octacosaoctaenoic acid,
      and by precursor ion scanning of ions at m/z 407, which was an ion corresponding
      to the structure of acyl of 28:8 acid (C27H39COO-). Based on these analyzes, it
      was found that out of more than a dozen lipid classes present in the total
      lipids, only two classes of neutral lipids, i.e. major triacylglycerols and minor
      diacylglycerols contain VLCPUFAs. In polar lipids, VLCPUFAs were identified only
      in phosphatidic acid (PA) and phosphatidyl choline (PC) or in their lyso-forms
      (LPA and LPC). Further analysis of individual lipid classes by reversed-phase
      high-performance liquid chromatography (RP-HPLC) showed the presence of
      triacylglycerols (TAGs) containing VLCPUFAs, i.e. molecular species of the sn
      28:7/28:8/28:8, sn-26:7/28:7/28:8, or sn-26:7/28:8/28:8 types. These TAGs are the
      longest and most unsaturated TAGs isolated from a natural source that have yet
      been synthesized. In the case of PA and PC, tandem MS identified sn-28:8/16:0-PA
      and sn-28:8/16:0-PC and the corresponding lyso-forms (28:8-LPC and 28:8-LPA). All
      these results indicate that TAGs containing VLCPUFAs are biosynthesized in
      dinoflagellates in the same manner as in higher eukaryotic organisms, which means
      that the PA, after conversion to DAG, serves as a precursor in the biosynthesis
      of other phospholipids, e.g. PC, and, after further acylation, also of TAG.

PMID- 28433955
TI  - 5,6,7,8-Tetrahydro-2-(2-phenylethyl)chromones from artificial agarwood of
      Aquilaria sinensis and their inhibitory activity against acetylcholinesterase.
AB  - Thirteen previously undescribed 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones
      named tetrahydrochromone A-M, together with nine known ones, were isolated from
      artificial agarwood (induced by holing) originating from Aquilaria sinensis
      (Lour.) Gilg. The structures of these compounds were unambiguously determined
      based on extensive NMR spectroscopic analyses, and the absolute configuration was
      resolved by CD analyses, X-ray crystallographic, chemical and Mosher's method.
      Tetrahydrochromone A, B, K-M, and Oxidoagarochromone An exhibited inhibitory
      activity against AChE with the percentage inhibition range from 17.5% to 47.9%
      (with Tacrine as the positive control; inhibition ratio: 66.7%) when tested at 50
      MUg/mL. Tetrahydrochromone A-E, F-J feature one methoxy and three hydroxys linked
      at the cyclohexene ring rather than usual four hydroxys, and tetrahydrochromone K
      M represent the first examples of 7,8-epoxy tetrahydrochromones.

PMID- 28433956
TI  - 40 years of angioplasty - remembering patients and pioneers.

PMID- 28433957
TI  - The translational journey of a new ultra-hydrophilic stent platform: what can we
      learn?

PMID- 28433958
TI  - Feasibility and safety of vitamin K antagonist monotherapy in atrial fibrillation
      patients undergoing transcatheter aortic valve implantation.
AB  - AIMS: We aimed to assess the efficacy and safety of vitamin K antagonist (VKA)
      monotherapy in atrial fibrillation (AF) patients undergoing transcatheter aortic
      valve implantation (TAVI). METHODS AND RESULTS: In 735 TAVIs since 2008 we
      identified 167 patients suffering from concomitant AF who received either VKA
      monotherapy (n=77), VKA plus single antiplatelet therapy (SAPT, n=41) or a triple
      anticoagulation regimen (n=49). Thromboembolic as well as bleeding complications
      were analysed for six months after TAVI. Only one minor bleeding and no
      thromboembolic events occurred after VKA therapy had been initiated post TAVI.
      Compared to patients being treated with additional either single or dual
      antiplatelet therapy, the incidence of major/life-threatening bleeding
      complications was significantly lower in the VKA mono group (0/77 [VKA mono] vs.
      3/41 [VKA+SAPT; p=0.04] vs. 4/49 [triple anticoagulation; p=0.02]). Analysis of a
      combined endpoint of post-procedural death, stroke, embolism and major bleeding
      revealed a significant superiority of VKA monotherapy compared to VKA plus SAPT
      or DAPT, respectively (5/77 vs. 9/41 [p=0.02] vs. 14/49 [p=0.002]). CONCLUSIONS:
      VKA therapy without additional antiplatelet treatment is effective and safe in AF
      patients undergoing TAVI.

PMID- 28433959
TI  - Single coronary artery arising from the right aortic sinus with dual LAD supply
      from separate branches.

PMID- 28433960
TI  - Multiple spontaneous intimal dissections with single left coronary artery and
      coronary artery aneurysm.

PMID- 28433961
TI  - Harnessing the medical humanities for experiential learning.
AB  - A month-long workshop on medical humanities was held in the Jorhat Medical
      College, Assam in September 2015. It employed experiential learning (both online
      and onsite) using humanities tools, such as the theatre of the oppressed, art,
      literature, reflective narratives, movies, the history of medicine, graphic
      medicine, poetry and diversity studies. As a result of the interactions, 28
      volunteer participants, comprising students and faculty members, wrote reflective
      narratives on doctor-patient relationships, produced a newsletter and a logo for
      their medical humanities group, and staged cultural performances and forum
      theatre. The narratives, participants' reflections and feedback received were
      subjected to qualitative analysis; the workshop was evaluated using Kirkpatrick's
      model. The participants learned to examine their attitudes and behaviour,
      communicate with their bodies, and experience respect for diversity. There was an
      improvement in their understanding of empathy, ethics and professionalism. The
      workshop achieved level-3 (behaviour) on Kirkpatrick's model, suggesting that
      such workshops can initiate a change in the ABCDE attributes (attitude,
      behaviour, communication, diversity, ethics and empathy) of medical
      professionals.

PMID- 28433962
TI  - Ten-minute snapshots - a team approach to teaching postgraduates about
      professional dilemmas.
AB  - As medical professionals, most of us face professional dilemmas that catch us
      unawares and are not discussed in medical training. One often learns about these
      dilemmas on one's own and deals with them with a common sense approach, rather
      than reflection. The professional dilemmas may concern receiving gifts from
      patients, handling issues of confidentiality or dealing with personal questions.
      There is seldom any formal instruction in competencies related to
      professionalism, especially in India. We adopted a team approach to provide
      training in these issues to postgraduate trainees in mental health and to engage
      them in discussion, using team feedback on snapshots of real-life professional
      situations, which were simulated through role play. We found that the trainees
      felt that these methods were acceptable and to their liking. However, a more
      formal method of assessing how this approach actually influences day-to-day
      practice must be evolved.

PMID- 28433963
TI  - Schuklenk's critique of the CIOMS guidelines: All procedure, no substance.

PMID- 28433964
TI  - Ethical management of substance use disorders: the Indian scenario.
AB  - Substance use disorders are among the most prevalent and emergent public health
      problems in India. The treatment of individuals with these disorders is
      associated with many ethical dilemmas. Due to the pervasiveness of substance use
      disorders, the majority of mental health professionals working in the area of
      addiction medicine face several ethical dilemmas. When discussing substance use
      disorders, it must be borne in mind that there are important differences between
      India and the western countries in terms of the social and cultural aspects, as
      well as the legislative framework and healthcare delivery system. In this paper,
      we discuss the common ethical dilemmas that practitioners of addiction medicine
      face when dealing with patients with substance use disorders. We use the
      principlist approach defined by the four ethics principles - autonomy,
      beneficence, nonmaleficence and justice - to deliberate upon these dilemmas and
      how they may be resolved. Further, we emphasise the need to sensitise
      practitioners to the importance of giving due consideration to the ethical
      aspects in their clinical work..

PMID- 28433965
TI  - National Health Policy 2017: a cautious welcome.
AB  - On March 15, 2017 the union cabinet approved the new National Health Policy. The
      next day a 28-page policy text and an accompanying 13-page situational analysis
      were placed in Parliament and in the public domain. To have, at all times, a
      health policy in place that shows a road map on how a nation would show
      "progressive realization" of health as a basic human right is an obligation under
      the International Covenant on Economic, Social and Cultural Rights. This is an
      international treaty adopted in 1976, to which India became a signatory in 1979,
      and this was one of the catalysts for the adoption of the first National Health
      Policy in 1983. The immediate political backdrop to the articulation of a
      National Health Policy 2017 (NHP 2017), replacing the 2002 policy, is that a new
      health policy and a national health assurance plan were both part of the BJP's
      electoral manifesto. It has taken close to 34 months after the government took
      office, and some 26 months after the draft was circulated for public discussion,
      to finally approve the policy. This is reflective of the considerable
      contestation and contradictory pressures, often almost evenly matched, that went
      into finalising this policy.

PMID- 28433966
TI  - Correction.

PMID- 28433968
TI  - Correction.

PMID- 28433967
TI  - Correction.

PMID- 28433969
TI  - Gastrocolic fistula in a child following corrosive acid ingestion.
AB  - Gastrocolic fistulas in children are most commonly seen after placement of a
      percutaneous endoscopic gastrostomy. We present a 14-year-old girl who developed
      a gastrocolic fistula following accidental corrosive acid ingestion. On
      evaluation of her symptoms, a barium swallow identified the gastrocolic fistula.
      It healed spontaneously in 3 months. This was both unexpected and remarkable. To
      the best of our knowledge this is the first case of a gastrocolic fistula
      occurring following corrosive ingestion.

PMID- 28433970
TI  - Simultaneous transient global amnesia and right MCA stroke after Valsalva
      manoeuvre.
AB  - A 61-year-old man suffered an episode of transient confusion and anterograde
      amnesia after a Valsalva-related manoeuvre. The MRI diffusion weighted imaging
      (DWI) sequences showed a left hippocampal and two right parietal lesions that
      were deemed as acute. The MR angiography disclosed a high-grade stenosis in the
      right middle cerebral artery as was described by a transcranial colour-coded
      ultrasound as well. Ultrasound investigation of the jugular veins showed a right
      jugular venous reflux after a Valsalva manoeuvre. The patient was diagnosed with
      transient global amnesia based on clinical grounds and the right parietal lesions
      were considered as silent strokes. The Valsalva manoeuvre could have played as a
      common trigger for both diseases.

PMID- 28433971
TI  - The seatbelt sign: early recognition may be life-saving.

PMID- 28433973
TI  - A 'limb-girdle muscular dystrophy' responsive to asthma therapy.

PMID- 28433972
TI  - Paraneoplastic jaundice and prostate cancer.
AB  - Cholestasis has numerous causes. We present the case of a 78-year-old man with a
      common diagnosis in this age group and gender but with an unusual presentation.
      There are only 11 articles published of patients with jaundice due to a
      paraneoplastic syndrome associated with prostate cancer. Interleukin 6 and other
      proinflammatory cytokines appear to contribute to the pathophysiology of this
      syndrome. Our patient remains symptom free 4 months after treatment initiation.

PMID- 28433974
TI  - Hypoactive-hypoalert behaviour and thalamic hypometabolism due to intracranial
      hypotension.
AB  - A 47-year-old man presented with a 9-year history of a hypoalert hypoactive
      behaviour syndrome, caused by the deep brain swelling variant of spontaneous
      intracranial hypotension. Along with apathy with retained cognition, he had
      stable ataxia, impaired upgaze and episodes of central apnoea. MRI brain showed a
      sagging brainstem, pointed ventricles and reduced angle between the vein of Galen
      and the straight sinus, but no meningeal enhancement or subdural collections. A
      dopamine transporter scan showed preganglionic dopamine receptor deficiency; a
      fluorodeoxy glucose positron emission tomography scan showed bilateral
      hypothalamic hypometabolism. This variant of spontaneous intracranial hypotension
      may alter deep brain functioning within the basal ganglia and thalamus, causing
      the hypoactive-hypoalert behaviour phenotype.

PMID- 28433975
TI  - Absolute benefits of empagliflozin in type 2 diabetes: a game changer?

PMID- 28433976
TI  - Isolated duodenal rupture: primary repair without diversion; is it safe? Review
      of literature.
AB  - Isolated duodenal rupture is a rare injury encountered among children following
      blunt abdominal trauma. Early diagnosis and treatment are essential to decrease
      the associated morbidity and mortality. The debate is about the optimum operative
      management. We report a 6-year-old child who presented with acute abdominal pain
      due to isolated duodenal injury following blunt abdominal trauma. Emergency
      laparotomy revealed duodenal rupture at the junction of the first and second part
      of duodenum and absence of any other visceral injuries. The duodenal injury was
      defined as grade III, that is, involving 75% of the circumference. We opted to
      perform primary repair of the injured duodenum in two layers alone without
      diversion. The abdominal cavity was drained using an open system drain next to
      the repair. Nasogastric and jejunostomy tubes were used postoperatively for
      gastric decompression and enteral feeding, respectively. The child had an
      uneventful recovery, was discharged well on the 10th postoperative day and no
      stenosis was found on long-term follow-up. The debate was whether to repair the
      defect primarily or to combine the repair with diversion. Early diagnosis, the
      isolated nature of the duodenal injury and the possibility of minimal
      contamination favoured primary repair of the defect without diversion. The good
      outcome attributed to these factors were in agreement with most of the
      literature.

PMID- 28433977
TI  - Pupilloplasty to prevent dexamethasone intravitreal implant migration to anterior
      chamber.

PMID- 28433978
TI  - Rugger-jersey spine in osteopetrosis.

PMID- 28433979
TI  - Lethal high: acute disseminated encephalomyelitis (ADEM) triggered by toxic
      effect of synthetic cannabinoid black mamba.
AB  - A previously well 25-year-old man presented with agitation, double incontinence
      and left-sided incoordination. His symptoms started after smoking a synthetic
      cannabinoid (black mamba) 5 days earlier. Over 48 hours, he developed aphasia,
      generalised hypertonia, hyper-reflexia and dense left hemiparesis. This
      progressed to profuse diaphoresis, fever, tachycardia, hypertension and a
      possible seizure necessitating admission to the intensive care unit. CT head and
      cerebrospinal fluid analysis were unremarkable. MRI brain demonstrated asymmetric
      multifocal hyperintense lesions in white and grey matter, which raised suspicions
      of acute disseminated encephalomyelitis (ADEM). An electroencephalogram showed
      widespread brain wave slowing, indicating diffuse cerebral dysfunction. Cerebral
      angiogram was normal. Toxicology analysis of the substance confirmed a potent
      synthetic cannabinoid NM2201, technically legal at the time. The patient made a
      slow but significant recovery after a course of intravenous methylprednisolone,
      intravenous immunoglobulins and oral steroids, and was later transferred to a
      rehabilitation bed.

PMID- 28433980
TI  - A paediatric case of bilateral mandibular condyle fracture presenting with bloody
      otorrhoea following trauma.
AB  - A 7-year-old boy presented to the emergency department with bilateral bloody
      otorrhoea after falling from his scooter. Skull base fracture was suspected. CT
      showed no evidence of skull base fracture but bilateral mandibular condyle and
      external acoustic canals fractures. We report this case to illustrate a rare
      possibility of bilateral external acoustic canal fracture associated with
      condylar fracture in trauma patients presented with bloody otorrhoea.

PMID- 28433981
TI  - Physical urticaria.

PMID- 28433982
TI  - Acute on chronic gastrointestinal bleeding: a unique clinical entity.
AB  - Gastrointestinal bleeding is defined in temporal-spatial terms-as acute or
      chronic, and/or by its location in the gastrointestinal tract. Here, we define a
      distinct type of bleeding, which we have coined 'acute on chronic'
      gastrointestinal bleeding. We prospectively identified all patients who underwent
      endoscopic evaluation for any form of gastrointestinal bleeding at a University
      Hospital. Acute on chronic bleeding was defined as the presence of new symptoms
      or signs of acute bleeding in the setting of chronic bleeding, documented as iron
      deficiency anemia. Bleeding lesions were categorized using previously established
      criteria. We identified a total of 776, 254, and 430 patients with acute,
      chronic, or acute on chronic bleeding, respectively. In patients with acute on
      chronic gastrointestinal bleeding, lesions were most commonly identified in
      esophagus (28%), colon and rectum (27%), and stomach (21%) (p<0.0001 vs locations
      for acute or chronic bleeding). In those specifically with acute on chronic upper
      gastrointestinal bleeding (n=260), bleeding was most commonly due to portal
      hypertensive lesions, identified in 47% of subjects compared with 29% of acute
      and 25% of chronic bleeders, (p<0.001). In all patients with acute on chronic
      bleeding, 30-day mortality was less than that after acute bleeding alone (2%
      (10/430) vs 7% (54/776), respectively, p<0.001). Acute on chronic
      gastrointestinal bleeding is common, and in patients with upper gastrointestinal
      bleeding was most often a result of portal hypertensive upper gastrointestinal
      tract pathology. Reduced mortality in patients with acute on chronic
      gastrointestinal bleeding compared with those with acute bleeding raises the
      possibility of an adaptive response.

PMID- 28433983
TI  - Pulmonary metastasis from renal epithelioid angiomyolipoma in the setting of
      breast cancer.
AB  - A 68-year-old woman presented with visible haematuria. Ultrasonography and
      triphasic CT revealed a 2.6 cm mass in the lower pole of the left kidney. A
      biopsy suggested low-grade renal cell carcinoma. Radical nephrectomy was
      performed and revealed an epithelioid angiomyolipoma. At year 3, the patient
      developed ductal carcinoma of the right breast and underwent a wide local
      excision and sentinel lymph node biopsy followed by chemotherapy and
      radiotherapy. 4 months later, she was noted to have a 1.6 cm nodule in the middle
      lobe of her right lung. The primary differential diagnosis was a breast cancer
      metastasis. Biopsy revealed a metastatic renal epithelioid angiomyolipoma. The
      patient elected to have stereotactic radiotherapy over surgical excision. Renal
      angiomyolipomata are generally regarded as benign tumours. In the present report,
      we describe the first case of pulmonary metastasis from renal epithelioid
      angiomyolipoma in the setting of breast cancer.

PMID- 28433984
TI  - Haemophagocytic lymphohistiocytosis presenting as HELLP syndrome: a diagnostic
      and therapeutic challenge.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal,
      haematological disorder, which can be clinically challenging to diagnose and
      manage. We report a case of HLH in a previously healthy 33-year-old primigravida.
      The patient presented at 22 weeks gestation with dyspnoea, abdominal pain,
      anaemia, thrombocytopenia and elevated liver enzymes suggestive of HELLP
      syndrome.HELLP, a syndrome characterised by haemolysis, elevated liver enzymes
      and low platelets is considered a severe form of pre-eclampsia. Despite delivery
      of the fetus, her condition deteriorated over 3-4 days with high-grade fever,
      worsening thrombocytopenia and anaemia requiring transfusion support. A bone
      marrow biopsy showed haemophagocytosis and a diagnosis of HLH was made. Partial
      remission was achieved with etoposide-based chemotherapy and complete remission
      following bone marrow transplantation. Eleven months post-transplant, the disease
      aggressively recurred, and the patient died within 3 weeks of relapse.

PMID- 28433985
TI  - Lingual hyperpigmentation after 5-fluorouracil chemotherapy.

PMID- 28433986
TI  - An unusual guest in a patient with Hodgkin's lymphoma.

PMID- 28433987
TI  - Radiofrequency Lesions through Deep Brain Stimulation Electrodes in Movement
      Disorders: Case Report and Review of the Literature.
AB  - BACKGROUND: Although there are few reports of radiofrequency lesions performed
      through deep brain stimulation (DBS) electrodes in patients with movement
      disorders, experience with this method is scarce. METHODS: We present 2 patients
      who had been previously treated with DBS of subthalamic nuclei (STN) and the
      ventral intermediate (VIM) nucleus of the thalamus for Parkinson's disease and
      essential tremor, respectively, and underwent a radiofrequency lesion through
      their DBS electrodes after developing a hardware infection. The authors conduct a
      review of the literature regarding this method. RESULTS: Both patients had a good
      clinical outcome after 20 and 8 months, respectively, as assessed by a reduction
      in Fahn-Tolosa-Marin Scale and Unified Parkinson's Disease Rating Scale scores.
      The second patient underwent a second DBS system implantation surgery after his
      radiofrequency treatment to optimize his management, achieving optimal clinical
      control with lower current and drug requirements than before the radiofrequency
      intervention. No adverse effects were observed. CONCLUSIONS: Radiofrequency
      lesions through DBS electrodes allow the creation of small and localized lesions.
      Its effectiveness and low-risk profile, in addition to its low cost, make this
      procedure suitable and a possible alternative in the therapeutic repertoire for
      the surgical treatment of movement disorders.

PMID- 28433988
TI  - Comparison of Choriocapillaris Flow Measurements between Two Optical Coherence
      Tomography Angiography Devices.
AB  - PURPOSE: To evaluate choriocapillaris (CC) perfusion in healthy subjects using 2
      different optical coherence tomography angiography (OCT-A) devices. PROCEDURES:
      Macular OCT-A imaging (36 eyes of 36 subjects) was performed using Optovue
      AngioVue and Zeiss AngioPlex devices. CC decorrelation signal index was assessed,
      and CC data were analyzed regarding intra-device variability, inter-device
      correlation, age, signal strength, and fields of view. RESULTS: The intra-device
      variability of CC measurements in the 3 * 3 mm2 field was 5.3 and 2.6% (Angiovue
      and Angioplex, coefficients of variation; 6 * 6 mm2: 8.0 and 2.8%, respectively).
      Mean CC decorrelation signal index in 3 * 3 mm2 was 104.3 +/- 6.7 (Angiovue) and
      81.3 +/- 9.2 (Angioplex) (6 * 6 mm2: 95.6 +/- 8.1, 81.1 +/- 6.5) with high
      correlation between both devices (3 * 3 mm2: p = 0.0053; 6 * 6 mm2: p = 0.0139).
      CC decorrelation signal index in 3 * 3 mm2 was significantly higher in subjects
      aged <=58 years compared to subjects aged >=59 years (Angiovue: 107.3 +/- 3.6,
      101.3 +/- 7.7, p = 0.0156; Angioplex: 84.6 +/- 7.6, 78.0 +/- 9.5, p = 0.0371).
      Signal strength was 64.6 +/- 8.9 (Angiovue) and 9.5 +/- 0.8 (Angioplex).
      CONCLUSION: Both devices showed low intra-device variability and a high inter
      device correlation. CC decorrelation signal index was negatively correlated with
      advancing age.

PMID- 28433990
TI  - Two-Dimensional Ultrasound Evaluation of the Fetal Cerebral Aqueduct: Improving
      the Antenatal Diagnosis and Counseling of Aqueductal Stenosis.
AB  - OBJECTIVE: To describe a technique for the visualization and measurement of
      cerebral aqueduct diameter through a 2D sagittal median plane, and to report its
      aspect and measurement in fetuses with aqueductal stenosis (AS). METHODS: This
      was a cross-sectional study of 207 morphologically normal fetuses in low-risk
      pregnancies between 20 and 36 weeks of gestation. The cerebral aqueduct was
      visualized transvaginally in a midsagittal plane, and measurements of its
      greatest diameter (ampulla) were taken independently by an expert and a nonexpert
      sonographer. In addition, the aqueduct morphology from 7 fetuses with AS and
      complete follow-up were compared to the reference range. RESULTS: Aqueductal
      measurements were obtained in 206 of 207 normal fetuses. Aqueductal growth
      occurred linearly with gestational age. Our method demonstrated excellent
      interobserver reproducibility. Among the 7 fetuses with AS, the aqueductal lumen
      could not be identified in 6 and had a funneling aspect in 1. DISCUSSION: Our
      study demonstrated that it is possible to visualize and measure the cerebral
      aqueduct directly through a 2D ultrasound median plane. In fetuses with severe
      ventriculomegaly, the morphology and width of this structure could represent a
      relevant tool in improving AS diagnosis, differentiating it from other causes of
      significant ventricular dilation that carry a different outcome.

PMID- 28433989
TI  - Oral Contraceptives after Bariatric Surgery.
AB  - OBJECTIVE: Bariatric surgery offers a highly effective mode of treatment for
      obese patients. Some procedures such as bypass cause an alteration in normal
      gastrointestinal tract with possible consequences for the uptake of orally
      administered drugs. METHODS: We assessed the literature to ascertain whether the
      use of oral drugs and especially oral contraceptives is effective and adequate
      after bariatric surgery. RESULTS: The bioavailability of drugs could be affected
      by the solubility and pH of the modified medium after bariatric surgery and by
      the loss of gastrointestinal transporters. Bariatric surgery could potentially
      result in a transient change in the absorption of drugs such as analgesics,
      antibiotics, antiarrhythmics, anticoagulants, psychotropic, and oral
      contraceptive drugs. Effective contraception is especially critical in the
      postoperative period, and implants might be representing a safe contraceptive
      method in women undergoing bariatric surgery. CONCLUSION: Each drug will have to
      be evaluated with respect to its site of absorption and its mechanism of
      absorption, with special attention on parameters influencing the effectiveness of
      the absorption processes.

PMID- 28433991
TI  - The Effect of Traumatic Experiences and Psychiatric Symptoms on the Life
      Satisfaction of North Korean Refugees.
AB  - BACKGROUND: Successful adaptation of refugees to a new society can be hindered by
      traumatic experiences and psychiatric symptoms. This study aims to examine the
      relationship between trauma, psychiatric symptoms and life satisfaction of North
      Korean refugees resettled in South Korea. METHODS: A total of 211 North Korean
      refugees living in South Korea completed a series of questionnaires on the
      history of their previous traumatic experiences, life satisfaction in South
      Korea, depression, anxiety, somatization and post-traumatic stress disorder
      (PTSD) symptoms. RESULTS: North Korean refugees who had experienced more
      traumatic events were less satisfied with their economic status in South Korea.
      Severe depression, anxiety, somatization or PTSD symptoms negatively correlated
      with their overall satisfaction in South Korea. In the stepwise regression model
      including all psychiatric symptoms and the number of traumatic experiences as
      dependent variables, only anxiety, but not trauma, predicted lower life
      satisfaction in South Korea. CONCLUSIONS: Traumatic experiences of North Korean
      refugees negatively affected the life satisfaction, especially the economic
      satisfaction, in South Korea. Since the negative effect of trauma was mainly
      mediated by psychiatric symptoms, the strategy of relieving psychiatric symptoms
      of traumatized refugees may help the adaptation of refugees.

PMID- 28433992
TI  - The Aachen Minipig: Phenotype, Genotype, Hematological and Biochemical
      Characterization, and Comparison to the Gottingen Minipig.
AB  - BACKGROUND: The pig is one of the most frequently used large animal models for
      biomedical research, especially in the field of translational research and
      surgical models. While standard livestock breeds are used in short-term and acute
      studies, minipig breeds are the preferred breeds in long-term and chronic studies
      due to their limited growth and body weight. OBJECTIVE: In consideration of the
      3R principle (refinement, reduction, replacement) and the increasing demand, the
      aim of this study was to generate a new, robust, non-specific-pathogen-free
      minipig breed, the Aachen minipig. METHODS: Phenotype, genotype, and
      hematological as well as clinical chemistry parameters were characterized, and
      reference values of the Aachen minipig were generated and compared to the values
      in the commonly used Gottingen minipig. Organ weights of the heart, kidney,
      liver, lung, spleen, and brain were determined using a laboratory balance. Blood
      samples were collected for hematology and clinical chemistry. Assessment of
      genetic diversity was performed by microsatellite markers. Nasal swabs were
      collected from 11 individual minipigs representing 6 races for DNA extraction.
      DNA was quantified and the identity and origin of the Aachen minipigs at the
      genomic level was determined by microsatellites. RESULTS: The Aachen minipig
      established here is based on the Mini-LEWE breed and consists of the Vietnamese
      potbelly pig, the Schwabisch Hallisch Landpig, the German Landrace, and the
      Minnesota minipig. Relative organ weights (lung, heart, kidneys, brain),
      hematology (hemoglobin, hematocrit, platelet count, mean corpuscular hemoglobin
      concentration, segmented neutrophils, lymphocytes, eosinophils, basophils), and
      clinical chemistry parameters (sodium, calcium, chloride, alkaline phosphatase,
      aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase,
      lactate dehydrogenase, triglycerides, blood urea nitrogen, creatinine, total
      bilirubin, total protein, creatine kinase) of the Aachen minipigs and the
      Gottingen minipigs were not significantly different. Significant differences
      where only seen in relative organ weights (liver, spleen), hematology (red blood
      cell count, mean corpuscular volume, mean corpuscular hemoglobin, white blood
      cell count, banded neutrophils, monocytes), and clinical chemistry parameters
      (inorganic phosphorus, potassium, glucose, cholesterol, albumin, amylase).
      CONCLUSION: The Aachen minipig is a suitable model for research due to its
      similarity to other minipig breeds, especially the Gottingen minipig. The
      reference values established in this study may be used for the comparison of
      scientific data and encourage the use of the Aachen minipig as an animal model
      for biomedical research.

PMID- 28433994
TI  - The cHS4 Chromatin Insulator Reduces the Rate of Retroviral Vector-Mediated Gene
      Dysregulation Associated with Aberrant Vector Transcription.
AB  - Integrating gammaretroviral vectors can dysregulate the expression of cellular
      genes through a variety of mechanisms, leading to genotoxicity and malignant
      transformation. Although most attention has focused on the activation of cellular
      genes by vector enhancers, aberrant fusion transcripts involving cellular gene
      sequences and vector promoters, vector splice elements, and vector transcription
      termination sequences have also been mechanistically associated with dysregulated
      expression of cellular genes. Chromatin insulators have emerged as an effective
      tool for reducing the frequency of vector-mediated genotoxicity and malignant
      transformation and have been shown to block the activation of cellular genes by
      vector enhancers. We report here evidence that flanking a gammaretroviral
      reporter vector with the cHS4 chromatin insulator also reduces the frequency of
      vector-mediated cellular gene dysregulation associated with aberrant vector
      transcripts, including vector transcription run-through and aberrant splicing. We
      demonstrate that the cHS4 element does not function to terminate transcription
      directly, implicating other mechanisms for this activity.

PMID- 28433995
TI  - Effect of Prophylactic Dialysis on Morbidity and Mortality in Non-Dialysis
      Dependent Patients after Coronary Artery Bypass Grafting: A Pilot Study.
AB  - BACKGROUND/AIMS: Coronary artery bypass grafting (CABG) is associated with an
      increased risk of morbidity and mortality in patients with pre-existing renal
      dysfunction. Numerous measures have been implemented to overcome this problem;
      however, no improvement in outcomes has been achieved. This study was aimed at
      investigating the effects of prophylactic dialysis on mortality and morbidity in
      these patients. METHODS: This randomized-controlled clinical trial enrolled 88
      non-dialysis-dependent patients with chronic kidney disease awaiting CABG
      surgery. Thirty-nine randomly selected patients received dialysis 3 times prior
      to surgery, and 49 patients formed the control group. Kaplan-Meier analysis and
      Cox proportional-hazards models were used to identify factors associated with
      survival. RESULTS: There was no significant difference in the development of
      morbidities between the groups (p = 0.413). A significant difference was evident
      in the average survival time (p = 0.037). Cox proportional-hazards models
      determined that the hazard ratio of death after surgery was 10.854-fold greater
      in non-dialysis patients than in patients who received dialysis (hazard ratio =
      2). CONCLUSION: Prophylactic dialysis prior to CABG decreases mortality, but does
      not affect morbidity, in patients with renal insufficiency.

PMID- 28433993
TI  - Determinants of Perceived Stress in Individuals with Obesity: Exploring the
      Relationship of Potentially Obesity-Related Factors and Perceived Stress.
AB  - OBJECTIVE: Associations of specific types of stress with increased food intake
      and subsequent weight gain have been demonstrated in animal models as well as in
      experimental and epidemiological studies on humans. This study explores the
      research question of to what extent potentially obesity-related factors determine
      perceived stress in individuals with obesity. METHODS: N = 547 individuals with
      obesity participated in a cross-sectional study assessing perceived stress as the
      outcome variable and potential determinants of stress related to obesity. Based
      on the available evidence, a five factorial model of 'obesity-related obesogenic
      stressors' was hypothesized, including the dimensions, 'drive for thinness',
      'impulse regulation', 'ineffectiveness', 'social insecurity', and 'body
      dissatisfaction'. The model was tested using multiple linear regression analyses.
      RESULTS: The five factorial model of 'potentially obesity-related stressors'
      resulted in a total variance explanation of adjusted R2 = 0.616 for males and
      adjusted R2 = 0.595 for females for perceived stress. The relative variance
      contribution of the five included factors differed substantially for the two
      sexes. CONCLUSION: The findings of this cross-sectional study support the
      hypothesized, potentially obesity-related factors: 'drive for thinness', 'impulse
      regulation', 'ineffectiveness', 'social insecurity', and 'body dissatisfaction'
      as relevant determinants of perceived stress in individuals with obesity.

PMID- 28433997
TI  - Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats.
AB  - BACKGROUND: The liver can heal up to restitutio ad integrum following damage
      resulting from various causes. Different studies have demonstrated the protective
      effect of argon on various cells and organs. To the best of our knowledge, the
      organ-protective effects of the noble gas argon on the liver have not yet been
      investigated, although argon appears to influence signal paths that are well
      known mediators of liver regeneration. We hypothesized that argon inhalation
      prior to partial hepatectomy (70%) has a positive effect on the initiation of
      liver regeneration in rats. METHODS: Partial hepatectomy (70%) with or without
      inhaled argon (50 vol%) was performed for 1 h. Liver tissue was harvested after
      3, 36, and 96 h to analyze the mRNA and protein expression of hepatocyte growth
      factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-alpha, and
      extracellular signal-regulated kinase 1/2. Histological tissue samples were
      prepared for immunohistochemistry (bromodeoxyuridine [BrdU], Ki-67, and TUNEL)
      and blood was analyzed regarding the effects of argon on liver function.
      Statistical analyses were performed using 1-way ANOVA followed by the post hoc
      Tukey-Kramer test. RESULTS: After 3 h, the primary outcome parameter of
      hepatocyte proliferation was significantly reduced with argon 50 vol% inhalation
      in comparison to nitrogen inhalation (BrdU: 15.7 +/- 9.7 vs. 7.7 +/- 3.1 positive
      cells/1,000 hepatocytes, p = 0.013; Ki-67: 17.6 +/- 13.3 vs. 4.7 +/- 5.4 positive
      cells/1,000 hepatocytes, p = 0.006). This was most likely mediated by significant
      downregulation of HGF (after 3 h: 5.2 +/- 3.2 vs. 2.3 +/- 1.0 fold, p = 0.032;
      after 96 h: 2.1 +/- 0.5 vs. 1.3 +/- 0.3 fold, p = 0.029) and IL-6 (after 3 h:
      43.7 +/- 39.6 vs. 8.5 +/- 9.2 fold, p = 0.032). Nevertheless, we could detect no
      significant effect on the weight of the residual liver, liver-body weight ratio,
      or liver blood test results after argon inhalation. CONCLUSION: Impairment of
      liver regeneration was apparent after argon 50 vol% inhalation that was most
      probably mediated by downregulation of HGF and IL-6 in the initial phase.
      However, the present study was not adequately powered to prove that argon has
      detrimental effects on the liver. Further studies are needed to evaluate the
      effects of argon on livers with preexisting conditions as well as on ischemia
      reperfusion models.

PMID- 28433996
TI  - Factor XII as a Risk Marker for Hemorrhagic Stroke: A Prospective Cohort Study.
AB  - BACKGROUND: Coagulation factor XII (FXII) is involved in pathological thrombus
      formation and is a suggested target of anticoagulants. It is unclear whether FXII
      levels are correlated with cardiovascular risk factors and whether they are
      associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim
      of this study was to investigate the correlation between FXII and cardiovascular
      risk factors in the general population. We also aimed to study the associations
      between FXII levels and future myocardial infarction and ischemic and hemorrhagic
      stroke. METHODS: This prospective cohort study measured FXII levels in 1,852
      randomly selected participants in a health survey performed in northern Sweden in
      1994. Participants were followed until myocardial infarction, stroke, death, or
      until December 31, 2011. RESULTS: During the median follow-up of 17.9 years, 165
      individuals were diagnosed with myocardial infarction, 108 with ischemic stroke,
      and 30 with hemorrhagic stroke. There were weak correlations between FXII and
      body mass index, cholesterol, and hypertension. There was no association between
      FXII and myocardial infarction or ischemic stroke, neither in univariable Cox
      regression analysis nor after adjustment for age, sex, smoking, body mass index,
      cholesterol, hypertension, and diabetes. In univariable Cox regression analysis,
      the hazard ratio for the association between FXII levels and hemorrhagic stroke
      was 1.42 per SD (95% confidence interval: 0.99-2.05). In the multivariable model,
      higher levels of FXII were associated with increased risk of hemorrhagic stroke
      (hazard ratio 1.51 per SD; 95% confidence interval: 1.03-2.21). CONCLUSION: We
      found an independent association between FXII levels and the risk of hemorrhagic
      stroke, but not between FXII levels and ischemic stroke or myocardial infarction.

PMID- 28433998
TI  - Interferon-beta 1a Modulates Expression of RAGE but Not S100A12 and Nuclear
      Factor-kappaB in Multiple Sclerosis Patients.
AB  - OBJECTIVES: Interferon-beta 1a (IFN-beta 1a) is a common strategy therapy for
      multiple sclerosis (MS) with unknown mechanisms. S100A12 (S100 calcium-binding
      protein A12) is a damage-associated molecular pattern molecule which binds to its
      receptor, RAGE (receptor for advanced glycation end products), and activates
      nuclear factor-kappaB (NF-kappaB). NF-kappaB is transcribed from proinflammatory
      molecules, which may participate in the pathogenesis of MS. Therefore, the aims
      of this study were to compare mRNA levels of S100A12, RAGE, and NF-kappaB in
      newly diagnosed MS patients with healthy controls and determine whether IFN-beta
      1a therapy affects the expression of the molecules. METHODS: S100A12, RAGE, and
      NF-kappaB mRNA levels in 30 new cases of untreated MS patients and 35 healthy
      controls were evaluated using the real-time PCR technique. The mRNA levels were
      also evaluated in the MS patients after 6 months of IFN-beta 1a therapy. RESULTS:
      S100A12, RAGE, and NF-kappaB mRNA levels were significantly decreased in the new
      cases of untreated MS patients in comparison to healthy controls. IFN-beta 1a
      therapy results in upregulation of RAGE in MS patients, but not S100A12 and NF
      kappaB. CONCLUSIONS: It appears that S100A12 participates in the pathogenesis of
      MS, and it seems that IFN-beta 1a modulates immune responses in an S100A12
      independent manner. Based on the reported anti-inflammatory effects of RAGE, it
      seems that RAGE may be considered as a mechanism by IFN-beta 1a to modulate
      immune responses. NF-kappaB is produced permanently in the human cells and is
      inactive in the cytoplasm; therefore, the effects of IFN-beta 1a may be related
      to its functions rather than expressions.

PMID- 28433999
TI  - Circadian Plasma Cortisol Measurements Reflect Severity of Hypercortisolemia in
      Children with Different Etiologies of Endogenous Cushing Syndrome.
AB  - BACKGROUND: The utility of circadian cortisol variation in estimating the degree
      of hypercortisolemia in different forms of endogenous Cushing syndrome (CS) has
      not been evaluated in children yet. METHODS: A retrospective cohort study,
      including children who underwent surgery due to CS (n = 115), was divided into
      children with a pituitary adenoma (Cushing disease) (n = 88), primary adrenal CS
      (n = 21), or ectopic adrenocorticotropin- or corticotropin-releasing hormone
      (ACTH-/CRH)-secreting tumors (n = 6). Circadian plasma cortisol measurements were
      obtained at 11: 30 p.m. and at midnight, and at 7: 30 and 8: 00 a.m. The ratios
      between the morning and late-night concentrations were calculated. RESULTS:
      Plasma cortisol early-morning and midnight (AM/PM) ratios negatively correlated
      with 24-h urinary free cortisol (UFC) collections among the full study population
      and in each of the individual etiologies. Plasma ACTH concentrations positively
      correlated with plasma cortisol AM/PM ratios among patients with ACTH-independent
      CS. Finally, patients with primary pigmented nodular adrenocortical disease
      showed no correlation between UFC collections and the plasma cortisol AM/PM
      ratio, in contrast with other etiologies for primary adrenal CS, which showed a
      strong negative correlation between them. CONCLUSION: Our study shows the
      association between the plasma cortisol AM/PM ratio and the degree of
      hypercortisolemia in children with CS.

PMID- 28434000
TI  - Apolipoprotein A1 Inhibits the TGF-beta1-Induced Endothelial-to-Mesenchymal
      Transition of Human Coronary Artery Endothelial Cells.
AB  - OBJECTIVE: Transforming growth factor beta1 (TGF-beta1) is the major cytokine for
      stimulating endothelial cells (ECs) to transdifferentiate to mesenchymal cells
      (MCs) in the process known as endothelial-to-mesenchymal transition (EndMT).
      Recently, TGF-beta1-induced EndMT has been implicated in the pathogenesis of
      atherosclerosis (AS). It has been identified that apolipoprotein A1 (ApoA-I)
      obstructs TGF-beta1-induced endothelial dysfunction, providing a protective
      effect for ECs and also anti-AS activity. However, the exact role of ApoA-I in
      TGF-beta1-induced EndMT is not clear. In this study, we aimed to investigate
      whether ApoA-I can modulate TGF-beta1-induced EndMT in human coronary artery ECs
      (HCAECs). METHODS AND RESULTS: The HCAECs were treated with TGF-beta1 with or
      without ApoA-I. Morphological changes in HCAECs and the expression of EndMT
      related markers were evaluated. HCAECs treated with TGF-beta1 were found to
      transform to MC morphology, with inconspicuous expression of EC markers such as
      vascular endothelial cadherin and CD31, and conspicuous expression of fibroblast
      specific protein 1 (FSP-1) and alpha-smooth muscle actin. The treatment of HCAECs
      with ApoA-I inhibited the TGF-beta1-induced EndMT, and elevated expression of EC
      markers was observed but reduced expression of MC markers. Moreover, ApoA-I
      impeded the expression level of Slug and Snail, crucial transcriptional factors
      of EndMT, and it inhibited the TGF-beta1-induced phosphorylation of Smad2 and
      Smad3 which affected the EC morphology. In addition, the knockdown of ABCA1 by
      RNA interference eliminated the inhibition effect of ApoA-I on TGF-beta1-induced
      EndMT. CONCLUSIONS: Our findings revealed a novel mechanism for the ApoA-I
      protective effect on endothelium function via the inhibition of TGF-beta1-induced
      EndMT. This might provide new insights for developing strategies for modulating
      AS and vascular remodeling.

PMID- 28434001
TI  - Antibiotic Decision in Severe Chronic Obstructive Pulmonary Disease
      Exacerbations.

PMID- 28434002
TI  - In situ Hearing Tests for the Purpose of a Self-Fit Hearing Aid.
AB  - This study investigated the potential and limitations of a self-fit hearing aid.
      This can be used in the "developing" world or in countries with large distances
      between the hearing-impaired subjects and the professional. It contains an on
      board tone generator for in situ user-controlled, automated audiometry, and other
      tests for hearing aid fitting. Twenty subjects with mild hearing losses were
      involved. In situ audiometry showed a test-retest reliability (SD <3.7 dB) that
      compared well with the precision of diagnostic audiometry using headphones. There
      was good correspondence (SD <5.2 dB) with traditional pure-tone audiometry. In
      situ loudness scaling yielded important information about suprathreshold
      perception, which will have an added value for the selection of compression and
      the selection of maximum power output to be allowed in hearing aids.

PMID- 28434003
TI  - Cytotoxic Effects of Transthyretin Aggregates in an Epidermoid Cell Line.
AB  - OBJECTIVE: Skin amyloid deposits can occur as part of systemic amyloidoses
      including those involving misfolded- aggregated transthyretins (agTTR).
      Pathological effects of agTTR on the skin are not well understood. The main
      objective of the current study was to examine the toxicity of agTTR upon a human
      keratinocyte cell line. METHODS: Cells were analyzed for indicators of oxidative
      stress after treatment with normal soluble TTR or the same pre-aggregation
      concentration of agTTR. Hydrogen peroxide production was analyzed as an indicator
      for the involvement of reactive oxygen species. RESULTS: Treatment of cells with
      agTTR significantly increased hydrogen peroxide production (p < 0.05 vs.
      controls). Glutathione (GSH) and catalase were analyzed as indicators of
      endogenous cellular antioxidant activity. Treatment of cells with agTTR resulted
      in significant decreases in both catalase activity and GSH levels (p < 0.05 vs.
      controls). CONCLUSION: agTTR disrupts redox balance and induces oxidative stress
      in these epidermoid cells.

PMID- 28434004
TI  - What Do Medical Students Know about Deep Brain Stimulation?
AB  - BACKGROUND: Deep brain stimulation (DBS) is an established therapy for movement
      disorders. It is currently under investigation in neuropsychiatric disorders.
      Neurophobia is a common phenomenon that might have a negative impact in medical
      education. Little is known about medical students' knowledge about DBS when they
      enter university and what they learn about it during their medical formation.
      METHODS: A 10-item questionnaire was designed. Questions addressed indications
      for DBS, costs of DBS, complications, the percentage of Parkinson disease (PD)
      patients who might profit from DBS, etc. Students at Hannover Medical School were
      asked to complete the questionnaire in the preclinical study period and in the
      last year of the study. RESULTS: Comparing the "early group" (204 students) and
      the "advanced group" (162 students), there was a significant gain of knowledge.
      More common disorders such as PD and tremor were known to be indications for DBS.
      Knowledge about the impact of DBS on specific symptoms in PD and about DBS
      targets was limited in both groups. CONCLUSIONS: DBS is partly known among
      medical students in the preclinical phase with a gain of knowledge during further
      study. Future studies on this topic addressing general practitioners as
      neurologists are needed to better understand why knowledge on DBS is still
      limited.

PMID- 28434005
TI  - Chorioamniotic Membrane Separation after Fetoscopic Laser Photocoagulation.
AB  - INTRODUCTION: This study aimed to investigate the risk factors, incidence, and
      influence on the perinatal outcome of chorioamniotic membrane separation (CMS)
      after fetoscopic laser photocoagulation (FLP). MATERIAL AND METHODS: This
      retrospective study included 312 women who underwent FLP for twin-to-twin
      transfusion syndrome (TTTS). Clinical records were used to review obstetrical
      examinations, complications, operative data, ultrasonographic findings, and
      perinatal and neonatal follow-up data in all patients. RESULTS: A total of 260
      cases of TTTS were analyzed. The incidence of CMS was 12.7% (33 cases). The only
      independent risk factor of CMS was performing FLP before 20 weeks of gestational
      age (GA) (odds ratio = 3.38 [1.44-7.93], p = 0.005). Concerning perinatal
      outcome, CMS was only related with increased risk of premature rupture of
      membranes (PROM) before 32 weeks (33.3 vs. 13.9%, p = 0.005), with no differences
      in GA at delivery and survival rate. DISCUSSION: In our cohort, the incidence of
      CMS after FLP was approximately 13%, with surgery before 20 weeks being the only
      risk factor identified. Although in our population CMS did not worsen perinatal
      outcome in terms of preterm delivery or survival, the preterm PROM rate was
      increased and this should be considered for the patients' management.

PMID- 28434007
TI  - 5th Update on Fabry Nephropathy: Biomarkers, Progression and Treatment
      Opportunities. April 25-27, 2017, Mexico City, Mexico: Abstracts.

PMID- 28434006
TI  - Unbiased Quantification of Subplate Neuron Loss following Neonatal Hypoxia
      Ischemia in a Rat Model.
AB  - BACKGROUND: Cellular targets of neonatal hypoxia-ischemia (HI) include both
      oligodendrocyte and neuronal lineages with differences in the patterns of
      vulnerable cells depending upon the developmental stage at which the injury
      occurs. Injury to the developing white matter is a characteristic feature of
      human preterm brain injury. Data are accumulating, however, for neuronal injury
      in the developing cerebral cortex. In the most widely used rodent model of
      preterm HI brain injury, conflicting data have been reported regarding the
      sensitivity of subplate neurons to early neonatal HI, with some reports of
      selective vulnerability and others that find no increased loss of subplate
      neurons in comparison with other cortical layers. Methods used to identify
      subplate neurons and quantify their numbers vary across studies. OBJECTIVE: To
      use recently developed cortical layer-specific markers quantified with definitive
      stereologic methods to determine the magnitude and specificity of subplate neuron
      cell loss following neonatal HI in a rodent model. METHODS: Postnatal day 2 (P2)
      rats underwent right common carotid artery coagulation followed by 2-3 h of
      hypoxia (5.6% oxygen). Categorically moderately injured brains were stained with
      subplate and cortical layer III-V markers (Complexin3 and Foxp1, respectively) at
      P8 and P21 (Foxp1 only). An Optical Fractionator was used to quantify subplate
      and middle/lower cortical neuronal numbers and these were compared across groups
      (naive control, hypoxia hemisphere, and HI hemisphere). RESULTS: Following HI at
      P2 in rats, the total Complexin3-expressing subplate neuron number decreases
      significantly in the HI hemisphere compared with naive controls or hypoxia alone
      (HI vs. control 26,747 +/- 7,952 vs. 35,468 +/- 8,029, p = 0.04; HI vs. hypoxia,
      26,747 +/- 7,952 vs. 40,439 +/- 7,363, p = 0.003). In contrast, the total Foxp1
      expressing layer III-V cell number did not differ across the 3 conditions at P8
      (HI vs. control 1,195,085 +/- 436,609 vs. 1,234,640 +/- 178,540, p = 0.19; HI vs.
      hypoxia, 1,195,085 +/- 436,609 vs. 1,289,195 +/- 468,941, p = 0.35) and at P21
      (HI vs. control 1,265,190 +/- 48,089 vs. 1,195,632 +/- 26,912, p = 0.19; HI vs.
      hypoxia, 1,265,190 +/- 48,089 vs. 1,309,563 +/- 41,669, p = 0.49). CONCLUSIONS:
      There is significant biological variability inherent in both the subplate neuron
      cell number and the pattern and severity of cortical injury following HI at P2 in
      rats. Despite this variability, the subplate neuron cell number is lower
      following P2 HI in animals with mild or moderate cortical injury, whereas the
      middle-to-lower-layer cortical neuronal number is unchanged. In more severe
      cases, neurons are lost from the lower cortical layers, suggesting a relative
      vulnerability of subplate neurons.

PMID- 28434009
TI  - Hypoxic-Ischaemic Encephalopathy and the Blood-Brain Barrier in Neonates.
AB  - This review aims to highlight a possible relationship between hypoxic-ischaemic
      encephalopathy (HIE) and the disruption of the blood-brain barrier (BBB).
      Inflammatory reactions perpetuate a large proportion of cerebral injury. The
      extent of injury noted in HIE is not only determined by the biochemical cascades
      that trigger the apoptosis-necrosis continuum of cell death in the brain
      parenchyma, but also by the breaching of the BBB by pro-inflammatory factors. We
      examine the changes that contribute to the breakdown of the BBB that occur during
      HIE at a macroscopic, cellular, and molecular level. The BBB is a permeability
      barrier which separates a large majority of brain areas from the systemic
      circulation. The concept of a physiological BBB is based at the anatomical level
      on the neurovascular unit (NVU). The NVU consists of various cellular components
      that jointly regulate the exchanges that occur at the interface between the
      systemic circulation and the brain parenchyma. There is increased understanding
      of the contribution of the components of the NVU, e.g., astrocytes and pericytes,
      to the maintenance of this physiological barrier. We also explore the development
      of therapeutic options in HIE, such as harnessing the transport systems in the
      BBB, to enable the delivery of large molecules with molecular Trojan horse
      technology, and the reinforcement of the physical barrier with cell-based therapy
      which utilizes endothelial progenitor cells and stem cells.

PMID- 28434008
TI  - Impact of Weight-Related Discrimination, Body Dissatisfaction and Self-Stigma on
      the Desire to Weigh Less.
AB  - AIM: Currently, health care professionals plead for stabilization of weight and
      improving health conditions rather than focusing on weight loss only. Individuals
      with obesity have been shown to report weight loss goals that are much higher
      than what has been suggested by guidelines. The aim was to determine whether
      weight discrimination and body dissatisfaction have an impact on how much weight
      an individual with obesity wants to lose. METHODS: In this representative
      telephone survey, 878 participants with obesity were asked about their
      experiences with weight stigma, their body image concerns, and about the amount
      of weight they would like to weigh using random digital dialing and Kish
      selection grid to ensure random selection of participants. RESULTS: Regression
      analysis reveals that being female, having a higher BMI, being younger, and
      trying to lose weight was related to a greater discrepancy between current weight
      and desired weight. The discrepancy between current weight and desired weight was
      greater when participants reported discrimination due to their weight as well as
      internalized stigma and body image concerns. CONCLUSION: Independent on the
      weight loss method, treating obesity should include realistic weight loss goals
      without being affected by social pressure or weight stigma, especially since
      stigma can result in further weight gain and decline health issues related to
      obesity and overweight.

PMID- 28434010
TI  - Dynamic Analysis of Kidney Function and Its Correlation with Nutritional
      Indicators in a Large Sample of Hospitalized Elderly Patients.
AB  - BACKGROUND The aim of this study was to analyze changes in kidney function and
      its correlation with nutritional metabolism indicators in hospitalized elderly
      patients in a large medical center over the past 7 years. MATERIAL AND METHODS
      The renal function of patients over 60 years old in the Chinese PLA General
      Hospital in 2008, 2011, and 2014 were comparatively analyzed. The hemoglobin,
      serum albumin, triglycerides, cholesterol, uric acid, and urea nitrogen data were
      collected and used as the nutritional metabolism indicators. In addition, the
      correlation between these indicators and the eGFR was analyzed. RESULTS The
      numbers of patients who received kidney function assessments in the 3 years were
      15 752, 23 539, and 49 828; their mean ages were 69.97+/-6.99, 69.51+/-7.11, and
      69.45+/-7.74 years. The median values of serum creatinine were 75.4, 76.5, and
      77.5 MUmol/L in the men and 59.6, 60.7, and 62.1 MUmol/L in the women. The eGFR
      in both sexes demonstrated a gradual decreasing trend over the 3 years. According
      to the CKD staging method, analysis of the different percentages of eGFR
      intervals in the patients showed that the percentages of the 3 groups with an
      eGFR lower than 60 mL/min/1.73 m2 exhibited a rising trend annually.
      Correlational analysis of the nutritional indicators showed that the correlations
      between Hb, ALB, TG, TC, Ur, and BUN with an eGFR lower than 60 mL/min/1.73 m2
      were 0.582, 0.780, 1.219, 1.364, 2.180, and 3.677, respectively. CONCLUSIONS
      Serum creatinine showed a gradually increasing trend over the 3 study years. The
      CKD-EPI equation calculation results showed that the eGFR in elderly people of
      both sexes gradually decreased. Reduction of hemoglobin and albumin was a risk
      factor for decreased kidney function, while increases in uric acid and blood
      lipids affected the progression of renal insufficiency.

PMID- 28434011
TI  - Management of Coxa Vara Septica and Pseudoarthrosis of the Femoral Neck: A Case
      Report.
AB  - BACKGROUND Coxa vara and pseudoarthrosis of the femoral neck after septic hip
      arthritis is a very rare disease. The aim of this study was to present a case
      with pseudoarthrosis of the femoral neck, with coxa vara after neonatal septic
      arthritis of the right hip, and treatment of the pseudarthrosis with proximal
      femoral valgus osteotomy. CASE REPORT A 12-month-old female, who had suffered
      neonatal septic arthritis with a five-day history of fever and painful right hip
      now demonstrated painless limping to the right hip, pelvic obliquity,
      Trendelenburg-Duchenne gait, limitation of hip abduction, lower-extremity length
      discrepancy with 3.0 cm of shortening of right femur, and walking on her tiptoes.
      In addition, a viable femoral head, coxa vara, and pseudoarthrosis of the femoral
      neck were observed. At the age of 26-months, the patient had a realignment valgus
      osteotomy of the proximal femur and adductor tenotomy was performed. At the last
      follow-up postoperative evaluation, at the age of four and a half years, the
      patient showed successful consolidation of pseudoarthrosis, correction of
      Trendelenburg gait, restored right lower extremity alignment, and corrected lower
      extremity length discrepancy. CONCLUSIONS In the case of coxa vara and
      pseudoarthrosis of the femoral neck, realignment of the proximal femoral valgus
      osteotomy and bone grafting of the pseudoarthrosis resulted in ossification of
      the femoral neck as the epiphyseal plate was placed at right angle to the
      compressive forces.

PMID- 28434012
TI  - Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor
      5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma).
AB  - BACKGROUND Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of
      hyperthyroidism. Somatostatin analogs have proved to be effective for inhibiting
      pituitary hormones secretion, working via interactions with somatostatin
      receptors (SSTRs). Moreover, antiproliferative activity of somatostatin analog is
      now demonstrated in several studies. In the present study, we determined the
      relative predominance of SSTR2 and SSTR5 subtypes among the different types of
      adenomas, especially TSHoma, and investigated the relationship between efficacy
      of short-term octreotide (OCT) treatment and SSTR expression. MATERIAL AND
      METHODS Serum hormone determinations and histological findings in resected tissue
      resulted in 5 diagnoses: 16 TSHomas, 8 acromegaly, 3 prolactinomas, 3
      corticotropinomas, 4 clinically nonfunctioning adenomas (NFPAs), and 4 normal
      pituitary specimens. IHC was performed on formalin-fixed and paraffin-embedded
      tissue in tissue microarrays. RESULTS IHC of SSTR subtypes in the different
      cohorts showed SSTR2 staining intensity scores higher than SSTR5 in TSHoma,
      acromegaly and prolactinoma, whereas the expression of SSTR5 was stronger than
      SSTR2 in corticotropinoma and NFPA. SSTR2 and SSTR5 expressions were
      significantly higher in TSHoma than in other pituitary adenomas. OCT treatment
      for a median of 8.4 days (range: 3-18 days) and with a total median dose of 1.9
      mg (range: 0.9-4.2 mg) showed a significant decrease of thyroid hormone levels
      (TSH [MUIU/ml] in all patients. Patients with low SSTR5 expression presented a
      significantly higher TSH suppression rate (P values <0.05). CONCLUSIONS The
      present data confirm that somatostatin analogs should be considered as a medical
      alternative to surgical treatment, especially in patients with TSHoma, and short
      term response to OCT therapy may be related to the expression of SSTR5.

PMID- 28434014
TI  - Prospective open-label evaluation of long-term low-dose doxycycline for difficult
      to-treat chronic rhinosinusitis with nasal polyps.
AB  - BACKGROUND: This study aimed to assess clinical outcomes of long-term low-dose
      oral doxycycline therapy in difficult-to-treat chronic rhinosinusitis with polyps
      (CRSwNP). METHODS: This was a prospective, open-label study of 60 patients with
      difficult-to-treat CRSwNP who had undergone endoscopic sinus surgery. Patients
      were divided into two groups: 28 received nasal steroids, saline irrigation, and
      doxycycline (200 mg on the first day, followed by 100 mg once daily) for 12
      weeks, while 30 received only nasal steroids and saline irrigation. The main
      outcome measure was an adequate effect size of doxycycline treatment on
      clinically meaningful significant improvement of SNOT-20. Other outcome measures
      were the SNOT-20, NOSE, and Lund-Kennedy scores. The following parameters were
      also analyzed: asthma, rhinitis, non-steroidal-exacerbated respiratory disease
      (NERD), and baseline serum IgG, IgA, IgE, IgM, ANCA, and eosinophil count.
      RESULTS: There was an adequate effect size of doxycycline treatment on clinically
      meaningful significant improvement of SNOT-20. Patients who received doxycycline
      also had significantly better outcomes regarding SNOT-20, NOSE, and Lund-Kennedy
      scores. There was a negative association among a clinically significant
      improvement of SNOT-20 and presence of asthma, NERD, and elevated serum IgE
      levels before treatment. CONCLUSION: These findings suggest that doxycycline may
      have a beneficial role for CRSwNP patients, especially for patients without
      asthma, NERD or high levels of serum IgE before treatment.

PMID- 28434015
TI  - Low lymphatic vessel density associates with chronic rhinosinusitis with nasal
      polyps.
AB  - OBJECTIVES: Chronic rhinosinusitis with and without nasal polyps (CRSwNP and
      CRSsNP) and antrochoanal polyps (ACP) are different upper airway inflammation
      phenotypes with different pathomechanisms. In order to understand the development
      of tissue edema, the present study aimed to evaluate lymphatic vessel density in
      CRSsNP, CRSwNP and ACP. MATERIALS AND METHODS: 120 retrospective nasal and
      maxillary sinus specimens were stained immunohistochemically with a von
      Willebrand factor polyclonal antibody recognizing vascular and lymphatic
      endothelium, and with a podoplanin monoclonal antibody recognizing lymphatic
      endothelium. Vessels were studied by microscopy in a blinded fashion, and the
      vessel density and the relative density of lymphatic vessels were calculated.
      Patient characteristic factors and follow-up data of in average 9 years were
      collected from patient records. RESULTS AND CONCLUSION: In the nasal cavity, the
      low absolute and relative density of vessels and of lymphatic vessels was
      associated with CRSwNP and ACP tissues compared to control inferior turbinate.
      This was observed also in the inflammatory hotspot area. In the maxillary sinus,
      lower absolute and relative density of lymphatic vessels associated with the
      CRSwNP phenotype. High lymphatic vessel density in polyp tissue associated with
      the need for revision CRS-surgery. As a conclusion, low density of lymphatic
      vessels distinguished patients with CRSwNP not only in the hotspot area of polyp
      tissue, but also in maxillary sinus mucosa. Yet, higher lymphatic vessel density
      seems to associate with polyp recurrence. Further studies are still needed to
      explore if formation of nasal polyps could be diminished by intranasal
      therapeutics affecting lymphangiogenesis.

PMID- 28434016
TI  - Chronic rhinosinusitis and mood disturbance.
AB  - BACKGROUND: This study is part of the Chronic Rhinosinusitis Epidemiology Study
      (CRES). The overarching aim is to determine factors that influence the onset and
      severity of chronic rhinosinusitis (CRS). The aim of this analysis is to
      determine whether those with CRS are more likely to report psychiatric morbidity
      and in particular mood disturbance compared with healthy controls. METHODS: CRES
      consists of a study-specific questionnaire regarding demographic and
      socioeconomic factors and past medical history as well as a nasal symptom score
      (SNOT-22) and SF-36 (QoL - quality of life tool). Both of these tools contain
      mental health or emotional well-being domains. Participants were specifically
      asked whether they had ever consulted with their General Practitioner for anxiety
      or depression. Questionnaires were distributed to patients with CRS attending ENT
      outpatient clinics at 30 centres across the United Kingdom from 2007-2013.
      Controls were also recruited at these sites. Patients were divided into subgroups
      of CRS according to the absence/presence of polyps (CRSsNPs/CRSwNPs) or allergic
      fungal rhinosinusitis (AFRS). RESULTS: Consultations with a family physician for
      depression or anxiety were higher amongst those with CRS than controls, but this
      was only significant for those with CRSsNPs. Odds ratio (OR) for CRSsNPs vs
      controls: 1.89; OR for CRSwNPs: 1.40. Patients with CRS showed significantly
      higher mental health morbidity than controls across the mental health and
      emotional wellbeing domains of the SF-36 and SNOT-22. Mean difference in the
      mental health domain of SF-36 was 8.3 for CRSsNPs and 5.3 for CRSwNPs. For the
      emotional domain of SNOT-22, differences were 7.7 and 6.3 respectively.
      CONCLUSIONS: Depression and anxiety are significantly more common in patients
      with CRS compared to healthy controls, especially in those with CRSsNPs. This
      added mental health morbidity needs consideration when managing these patients in
      primary and secondary care settings.

PMID- 28434017
TI  - Recurrent epistaxis: predicting risk of 30-day readmission, derivation and
      validation of RHINO-ooze score.
AB  - BACKGROUND: To derive and validate a predictive scoring tool (RHINO-ooze score)
      with good sensitivity and specificity in identifying patients with epistaxis at
      high risk of 30 day readmission and to enable risk stratification for possible
      definitive intervention. METHODS: Using medical databases, we searched for
      factors influencing recurrent epistaxis. The information ascertained together
      with our analysis of retrospective data on patients admitted with epistaxis
      between October 2013 and September 2014, was used as the derivation cohort to
      develop the predictive scoring model (RHINO-ooze score). The tool was validated
      by performing statistical analysis on the validation cohort of patients admitted
      with epistaxis between October 2014 and October 2015. Multiple linear regressions
      with backwards elimination was used to derive the predictive model. The area
      under the curve (AUC), sensitivity and specificity were calculated. RESULTS: 834
      admissions were encountered within the study period. Using the derivative cohort
      (n= 302) the RHINO-ooze score with a maximum score of 8 from five variables
      (Recent admission, Haemorrhage point unidentified, Increasing age over 70,
      posterior Nasal packing, Oral anticoagulant) was developed. The RHINO-ooze score
      had a chi-square value of 99.72 with a significance level of smaller than 0.0001
      and hence an overall good model fit. Comparison between the derivative and
      validation groups revealed similar rates of 30-day readmission between the
      cohorts. The sensitivity and specificity of predicting 30-day readmission in high
      risk patients with recurrent epistaxis (RHINO-ooze score equal/larger than 6) was
      81% and 84%, respectively. CONCLUSIONS: The RHINO-ooze scoring tool demonstrates
      good specificity and sensitivity in predicting the risk of 30 day readmission in
      patients with epistaxis and can be used as an adjunct to clinical decision making
      with regards to timing of operative intervention in order to reduce readmission
      rates.

PMID- 28434018
TI  - Low-dose nivolumab induced remission in refractory classical Hodgkin lymphoma.

PMID- 28434020
TI  - Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of
      patients with chronic heart failure.
AB  - AIMS: Beta-blockers are recommended for the treatment of chronic heart failure
      (CHF). However, it is disputed whether beta-blockers exert a class effect or
      whether there are differences in efficacy between agents. METHODS AND RESULTS:
      6010 out-patients with stable CHF and a reduced left ventricular ejection
      fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were
      identified from three registries in Norway, England, and Germany. In three
      separate matching procedures, patients were individually matched with respect to
      both dose equivalents and the respective propensity scores for beta-blocker
      treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%),
      and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol,
      and metoprolol, respectively. In univariable analysis of the general sample,
      bisoprolol and carvedilol were both associated with lower mortality as compared
      with metoprolol succinate (HR 0.80, 95% CI 0.71-0.91, p < 0.01, and HR 0.86, 95%
      CI 0.78-0.94, p < 0.01, respectively). Patients prescribed bisoprolol or
      carvedilol had similar mortality (HR 0.94, 95% CI 0.82-1.08, p = 0.37). However,
      there was no significant association between beta-blocker choice and all-cause
      mortality in any of the matched samples (HR 0.90; 95% CI 0.76-1.06; p = 0.20; HR
      1.10, 95% CI 0.93-1.31, p = 0.24; and HR 1.08, 95% CI 0.95-1.22, p = 0.26 for
      bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol
      vs. metoprolol succinate, respectively). Results were confirmed in a number of
      important subgroups. CONCLUSION: Our results suggest that the three beta-blockers
      investigated have similar effects on mortality amongst patients with CHF.

PMID- 28434019
TI  - Recent developments in olive (Olea europaea L.) genetics and genomics:
      applications in taxonomy, varietal identification, traceability and breeding.
AB  - KEY MESSAGE: The latest results in DNA markers application and genomic studies in
      olive. Olive (Olea europaea L.) is among the most ancient tree crops worldwide
      and the source of oil beneficial for human health. Despite this, few data on
      olive genetics are available in comparison with other cultivated plant species.
      Molecular information is mainly linked to molecular markers and their application
      to the study of DNA variation in the Olea europaea complex. In terms of genomic
      research, efforts have been made in sequencing, heralding the era of olive
      genomic. The present paper represents an update of a previous review work
      published in this journal in 2011. The review is again mainly focused on DNA
      markers, whose application still constitutes a relevant percentage of the most
      recently published researches. Since the olive genomic era has recently started,
      the latest results in this field are also being discussed.

PMID- 28434021
TI  - Correlation between proton pump inhibitors and risk of pyogenic liver abscess.
AB  - BACKGROUND/OBJECTIVE: Little is known about the relationship between proton pump
      inhibitors use and pyogenic liver abscess. The objective of this study was to
      evaluate the correlation between proton pump inhibitors use and pyogenic liver
      abscess in Taiwan. METHODS: This was a population-based case-control study using
      the database of the Taiwan National Health Insurance Program since 2000 to 2011.
      Subjects aged 20 to 84 who experienced their first episode of pyogenic liver
      abscess were enrolled as the case group (n = 1372). Randomly selected subjects
      aged 20 to 84 without pyogenic liver abscess were enrolled as the control group
      (n = 1372). Current use, early use, and late use of proton pump inhibitors was
      defined as subjects whose last one tablet for proton pump inhibitors was noted
      <=30 days, between 31 to 90 days and >=91 days before the date of admission for
      pyogenic liver abscess. Subjects who never received a prescription for proton
      pump inhibitors were defined as nonusers of proton pump inhibitors. A
      multivariable unconditional logistic regression model was used to measure the
      odds ratio and 95% confidence interval to evaluate the correlation between proton
      pump inhibitors use and pyogenic liver abscess. RESULTS: After adjusting for
      confounders, the adjusted odds ratio of pyogenic liver abscess was 7.59 for
      subjects with current use of proton pump inhibitors (95% confidence interval
      5.05, 11.4), when compared with nonusers. CONCLUSIONS: Current use of proton pump
      inhibitors is associated with a greater risk of pyogenic liver abscess.

PMID- 28434023
TI  - Developing a statistically powerful measure for quartet tree inference using
      phylogenetic identities and Markov invariants.
AB  - Recently there has been renewed interest in phylogenetic inference methods based
      on phylogenetic invariants, alongside the related Markov invariants. Broadly
      speaking, both these approaches give rise to polynomial functions of sequence
      site patterns that, in expectation value, either vanish for particular
      evolutionary trees (in the case of phylogenetic invariants) or have well
      understood transformation properties (in the case of Markov invariants). While
      both approaches have been valued for their intrinsic mathematical interest, it is
      not clear how they relate to each other, and to what extent they can be used as
      practical tools for inference of phylogenetic trees. In this paper, by focusing
      on the special case of binary sequence data and quartets of taxa, we are able to
      view these two different polynomial-based approaches within a common framework.
      To motivate the discussion, we present three desirable statistical properties
      that we argue any invariant-based phylogenetic method should satisfy: (1)
      sensible behaviour under reordering of input sequences; (2) stability as the taxa
      evolve independently according to a Markov process; and (3) explicit dependence
      on the assumption of a continuous-time process. Motivated by these statistical
      properties, we develop and explore several new phylogenetic inference methods. In
      particular, we develop a statistically bias-corrected version of the Markov
      invariants approach which satisfies all three properties. We also extend previous
      work by showing that the phylogenetic invariants can be implemented in such a way
      as to satisfy property (3). A simulation study shows that, in comparison to other
      methods, our new proposed approach based on bias-corrected Markov invariants is
      extremely powerful for phylogenetic inference. The binary case is of particular
      theoretical interest as-in this case only-the Markov invariants can be expressed
      as linear combinations of the phylogenetic invariants. A wider implication of
      this is that, for models with more than two states-for example DNA sequence
      alignments with four-state models-we find that methods which rely on phylogenetic
      invariants are incapable of satisfying all three of the stated statistical
      properties. This is because in these cases the relevant Markov invariants belong
      to a class of polynomials independent from the phylogenetic invariants.

PMID- 28434022
TI  - Effects of vestibular disorders on vestibular reflex and imagery.
AB  - The aim of this study was to establish the effect of vestibular lesion on
      vestibular imagery. Subjects were required to estimate verbally their passively
      travelled rotation angles in complete darkness, i.e., to activate vestibular
      imagery. During motion, the vestibulo-ocular reflex (VOR) was measured. Thus, we
      examined the coherence between the vestibulo-ocular reflex and self-rotation
      imagery, with vestibular-lesioned patients and healthy participants. Unilateral
      acute and chronic patients, bilateral patients, and healthy subjects were
      compared. The stimulus was a sequence of eight successive passive rotations, with
      four amplitudes (from 90 degrees  to 360 degrees ) in two directions. The VOR
      gain was lower in patients with unilateral lesions, for ipsilateral rotations.
      The healthy subjects had the highest gain and the bilateral group the lowest, on
      both rotation sides. Thanks to vestibular compensation after acute unilateral
      neuritis, the VOR gain increased in lesion side and decreased in healthy side,
      resulting in a similar gain in both sides. A deficit of vestibular imagery was
      found exclusively in patients with bilateral hyporeflexia, on both sides. The
      performance in vestibular imagery was good in the control group and correct in
      the unilateral patients. Finally, we found a significant correlation between the
      efficiency of the VOR and that of vestibular imagery, exclusively in the
      bilateral patients. The present study shows the complex relationship between
      vestibular imagery and the VOR. This imagery test contributes to another
      assessment of the spatial handicap of vestibular patients. It seems particularly
      interesting for patients with bilateral canal paresis and could be used to
      confirm this diagnosis.

PMID- 28434024
TI  - Chaotic dynamics in the seasonally forced SIR epidemic model.
AB  - We prove analytically the existence of chaotic dynamics in the forced SIR model.
      Although numerical experiments have already suggested that this model can exhibit
      chaotic dynamics, a rigorous proof (without computer-aided) was not given before.
      Under seasonality in the transmission rate, the coexistence of low birth and
      mortality rates with high recovery and transmission rates produces infinitely
      many periodic and aperiodic patterns together with sensitive dependence on the
      initial conditions.

PMID- 28434025
TI  - Erratum to: Identification of molecular variants of the nonrestoring restorer-of
      fertility 1 allele in sugar beet (Beta vulgaris L.).

PMID- 28434026
TI  - Erratum to: Transposon insertion resulted in the silencing of Wx-B1n in Chinese
      wheat landraces.

PMID- 28434027
TI  - Can ultrasound be used as the primary imaging in children with suspected Crohn
      disease?
AB  - BACKGROUND: There is growing literature on the use of ultrasound (US) for
      evaluation of Crohn disease in adults, but few studies have been conducted on
      children. Several studies demonstrated high accuracy of US in the diagnosis of
      Crohn disease. Using US as the primary screening imaging modality for Crohn
      disease can reduce health care costs, the need for sedation and ionizing
      radiation exposure. OBJECTIVE: The aim of our study is to determine if US can be
      used for screening evaluation of pediatric Crohn disease. MATERIALS AND METHODS:
      A prospective cohort study of pediatric patients undergoing MR enterography (MRE)
      for suspected or known history of Crohn disease was performed, with gray-scale
      and Doppler US of the terminal ileum done immediately before or after MRE. US
      images were interpreted by two radiologists (Reader 1 and Reader 2) not involved
      in image acquisition, in blinded and randomized fashion. US findings of Crohn
      disease including bowel wall thickening, wall stratification, increased
      vascularity on Doppler, lymphadenopathy, fat infiltration and extraintestinal
      complications were evaluated. MRE findings of terminal ileitis were considered
      the reference standard. Demographic data, body mass index (BMI), symptoms, and
      laboratory, endoscopic and histopathological data were obtained from electronic
      medical records. RESULTS: Forty-one patients (mean age: 13.7 years: 4.6-18.9
      years) were evaluated. Mean BMI was 21.2 (range: 13-40.2); 10 patients (24.3%)
      were either overweight or obese. Final diagnoses were Crohn disease (n=24),
      ulcerative colitis (n=4) and normal/non-inflammatory bowel disease-related
      diagnoses (n=13). US demonstrated sensitivity of 67% and 78% and specificity of
      78% and 83%, by Reader 1 and Reader 2, respectively. MRE sensitivity and
      specificity were 75% and 100%, respectively, compared to final
      clinicopathological diagnosis. Interobserver agreement between Reader 1 and
      Reader 2 was good (0.6< kappa <0.8). CONCLUSION: In screening for Crohn disease
      in children, US has limited sensitivity for detecting terminal ileitis.

PMID- 28434028
TI  - Reply to Offiah et al.: The triad of shaken baby syndrome.

PMID- 28434029
TI  - Health of midlife and older adults in China: the role of regional economic
      development, inequality, and institutional setting.
AB  - OBJECTIVES: To document the association between economic development, income
      inequality, and health-related public infrastructure, and health outcomes among
      Chinese adults in midlife and older age. METHODS: We use a series of multi-level
      regression models with individual-level baseline data from the China Health and
      Retirement Longitudinal Survey (CHARLS). Provincial-level data are obtained both
      from official statistics and from CHARLS itself. Multi-level models are estimated
      with different subjective and objective health outcomes. RESULTS: Economic growth
      is associated with better self-rated health, but also with obesity. Better health
      infrastructure tends to be negatively associated with health outcomes, indicating
      the likely presence of reverse causality. No supportive evidence is found for the
      hypothesis that income inequality leads to worse health outcomes. CONCLUSIONS:
      Our study shows that on top of individual characteristics, provincial variations
      in economic development, income inequality, and health infrastructure are
      associated with a range of health outcomes for Chinese midlife and older adults.
      Economic development in China might also bring adverse health outcomes for this
      age group; as such specific policy responses need to be developed.

PMID- 28434030
TI  - Spatial and Temporal Distributions of Air Pollutants and Size Distribution of
      Aerosols over Central and Eastern China.
AB  - The origins and spatial and temporal distributions of air pollutants (PM2.5,
      PM10, CO, SO2, NO2 and O3) during May to June of 2015 were investigated using
      data from 1490 monitoring sites in China. Aerosol number concentrations and
      meteorological data from Shijiazhuang, Nanjing, and Suzhou were combined with the
      MIX Asian emission data and the HYSPLIT model. Furthermore, the diurnal
      variation, size distribution, and main sources of air pollutants and aerosols
      were selectively characterized in the North China Plain (NCP) and the Yangtze
      River Delta (YRD). High values of particulate matter concentrations (PM),
      including PM2.5 and PM10, occurred in the northwestern and central regions of
      eastern China. Elevated PM2.5 and PM10 concentrations represented natural dust
      sources and anthropogenic resident, power plant, industry, and traffic emissions
      sources, respectively. The concentrated distributions of SO2 were similar to
      those of PM. The CO concentrations were distributed uniformly in China. High O3
      values occurred above the Qinghai province. During the observation period, the
      air masses mainly originated from the northwest NCP and from the southwest or
      northeastern ocean in the YRD, resulting in high concentrations of PM2.5, PM10,
      SO2, and CO in the NCP, the average values of which were 61.8 +/- 40.0, 118.8 +/-
      66.4, 24.1 +/- 24.6 MUg m-3, and 1.2 +/- 0.9 mg m-3, respectively, and were 1.2,
      1.4, 1.5, and 1.3 times larger than those in the YRD. NO2 had higher
      concentrations in the YRD with an average of 43.7 +/- 24.8 MUg m-3, which was 1.2
      times larger than that in the NCP. The diurnal variations of PM, NO2 and CO had
      bimodal distributions and SO2 and O3 had unimodal distributions in the NCP and
      YRD. The aerosol number concentrations had average values of 12,661 +/- 5266,
      11,189 +/- 5905, and 12,797 +/- 5931 cm-3 in Shijiazhuang, Nanjing, and Suzhou.
      Their diurnal variations displayed trimodal peaks at 18:00-21:00, 11:00-14:00,
      and 06:00-08:00, and their spectra distributions were all unimodal with peaks at
      60-70, 60-70, and 100-110 nm, respectively.

PMID- 28434031
TI  - FKBP51s signature in peripheral blood mononuclear cells of melanoma patients as a
      possible predictive factor for immunotherapy.
AB  - The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of
      the FKBP5 gene, resulting in increased expression of its variant 4 in the
      peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript
      is translated into the truncated FKBP51s protein. Given the importance of co
      inhibitory signalling in tumour immune escape, here we tested the potential for
      using FKBP51s expression to predict immunotherapy outcomes. To do this, we
      immunophenotyped PBMCs from 118 melanoma patients and 77 age- and sex-matched
      healthy controls. Blood samples were collected before patients underwent
      ipilimumab treatment. In 64 of the 118 patients, FKBP51s expression was also
      assessed in regulatory T cells (Tregs). We found that each PBMC subset analysed
      contained an FKBP51spos fraction, and that this fraction was greater in the
      melanoma patients than healthy controls. In CD4 T lymphocytes, the FKBP51sneg
      fraction was significantly impaired. Tregs count was increased in melanoma
      patients, which is in line with previous studies. Also, by analyses of FKBP51s in
      Tregs, we identified a subgroup of ipilimumab nonresponder patients (p = 0.002).
      In conclusion, FKBP51s-based immunophenotyping of melanoma patients revealed
      several profiles related to a negative immune regulatory control and identified
      an unknown Treg subset. These findings are likely to be useful in the selection
      of the patients that are candidate for immunotherapy.

PMID- 28434032
TI  - Diabetes, bone and glucose-lowering agents: basic biology.
AB  - Skeletal fragility often accompanies diabetes and does not appear to correlate
      with low bone mass or trauma severity in individuals with diabetes. Instead (and
      in contrast to those with osteoporotic bone disease), bone remodelling and bone
      turnover are compromised in both type 1 and type 2 diabetes, contributing to
      defective bone material quality. This review is one of a pair discussing the
      relationship between diabetes, bone and glucose-lowering agents; an accompanying
      review is provided in this issue of Diabetologia by Ann Schwartz (DOI:
      10.1007/s00125-017-4283-6 ). This review presents basic science evidence that,
      alongside other organs, bone is affected in diabetes via impairments in glucose
      metabolism, toxic effects of glucose oxidative derivatives (advance glycation end
      products [AGEs]), and via impairments in bone microvascular function and muscle
      endocrine function. The cellular and molecular basis for the effects of diabetes
      on bone are discussed, as is the impact of diabetes on the stem cell niche and
      fracture healing. Furthermore, the safety of clinically approved glucose-lowering
      therapies and the possibility of developing a single therapy that would be
      beneficial for both insulin sensitisation and diabetes bone syndrome are
      outlined.

PMID- 28434034
TI  - Erratum to: Houttuynia cordata aqueous extract attenuated glycative and oxidative
      stress in heart and kidney of diabetic mice.

PMID- 28434033
TI  - The gut microbiome as a target for prevention and treatment of hyperglycaemia in
      type 2 diabetes: from current human evidence to future possibilities.
AB  - The totality of microbial genomes in the gut exceeds the size of the human
      genome, having around 500-fold more genes that importantly complement our coding
      potential. Microbial genes are essential for key metabolic processes, such as the
      breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis
      of amino acids and vitamins, and production of neurotransmitters and hormones.
      During the last decade, evidence has accumulated to support a role for gut
      microbiota (analysed from faecal samples) in glycaemic control and type 2
      diabetes. Mechanistic studies in mice support a causal role for gut microbiota in
      metabolic diseases, although human data favouring causality is insufficient. As
      it may be challenging to sort the human evidence from the large number of animal
      studies in the field, there is a need to provide a review of human studies. Thus,
      the aim of this review is to cover the current and future possibilities and
      challenges of using the gut microbiota, with its capacity to be modified, in the
      development of preventive and treatment strategies for hyperglycaemia and type 2
      diabetes in humans. We discuss what is known about the composition and
      functionality of human gut microbiota in type 2 diabetes and summarise recent
      evidence of current treatment strategies that involve, or are based on,
      modification of gut microbiota (diet, probiotics, metformin and bariatric
      surgery). We go on to review some potential future gut-based glucose-lowering
      approaches involving microbiota, including the development of personalised
      nutrition and probiotic approaches, identification of therapeutic components of
      probiotics, targeted delivery of propionate in the proximal colon, targeted
      delivery of metformin in the lower gut, faecal microbiota transplantation, and
      the incorporation of genetically modified bacteria that express therapeutic
      factors into microbiota. Finally, future avenues and challenges for understanding
      the interplay between human nutrition, genetics and microbial genetics, and the
      need for integration of human multi-omic data (such as genetics, transcriptomics,
      epigenetics, proteomics and metabolomics) with microbiome data (such as strain
      level variation, transcriptomics, proteomics and metabolomics) to make
      personalised treatments a successful future reality are discussed.

PMID- 28434036
TI  - Acromion morphology and bone mineral density distribution suggest favorable
      fixation points for anatomic acromioclavicular reconstruction.
AB  - PURPOSE: Recent techniques for acromioclavicular (AC) joint reconstruction focus
      on additional AC cerclage to coracoclavicular (CC)-reconstructions. Due to the
      specific slim bone morphology at the acromion, there are concerns regarding these
      additional bone tunnels, as they may predispose to fracture and break out. The
      purpose of this study was to investigate anatomic properties of the acromion
      which may help improve surgical techniques directed at injuries to the AC joint.
      It was hypothesized that via measurements of thickness and density points of
      increased strength and support could be identified on the acromion. METHODS:
      Eighty-five fresh frozen cadaveric shoulders were used for this study. A
      standardized 3D-net was developed and thicknesses of the acromion were taken from
      defined points using a certified caliper. To define the acromial arch, the angle
      and radius of curvature between the antero-lateral, the highest point of the
      acromial arch and the postero-lateral aspect of the acromion were measured.
      Additional bone mineral density (BMD) evaluation was performed on 43 specimens in
      an anterio-posterior and latero-medial direction using 5-mm slices with a maximum
      of 10 and 6 slices, respectively. RESULTS: Median specimen age was 63.0 (range
      36) years (55 female, and 30 male). There was no statistical significance between
      male (62.0, range: 35 years) and female (64.5, range 32 years) regarding age
      (n.s.). Thickness of acromion points of interest were ranging from 3.5 to 24.3
      mm. Median radius of curvature of acromial arch for female was 48.2 (range 92.7)
      mm and 66.2 (range 85.6) for male (p = 0.019). The median angle for female
      specimens was 21.4 degrees  (range: 44.6 degrees ) and 23.3 degrees  (range 51.7
      degrees ) for male (p = 0.047). The latero-medial measurements showed significant
      difference between the region of interest (ROI): 1 and 4, 5, 6 (p = 0.001, p =
      0.001, p = 0.001), 2 and 4, 5, 6 (p = 0.007, p = 0.001, p = 0.001), 3 and 5, 6 (p
      = 0.001, p = 0.001), 4 and 5, 6 (p = 0.010, p = 0.001). Antero-posterior
      measurements showed significant difference between the ROI: 1 and 8 (p = 0.031).
      CONCLUSION: The posterior-medial acromion close to the AC joint revealed the
      highest BMD with an increasing density from lateral to medial. In combination
      with thickness measurements this region would support additional anatomical
      fixation of the AC joint using bone tunnels if necessary. CLINICAL RELEVANCE: To
      anatomically reproduce the insertions of the AC ligaments at the acromion, either
      bone tunnels or anchors are needed. Therefore, several techniques have been
      developed. This study provides the anatomical data for these techniques and
      confirms the reconstructive approach of techniques using anatomical points of
      fixation and orientation.

PMID- 28434035
TI  - Does soy protein affect circulating levels of unbound IGF-1?
AB  - INTRODUCTION: Despite the enormous amount of research that has been conducted on
      the role of soyfoods in the prevention and treatment of chronic disease, the
      mechanisms by which soy exerts its physiological effects are not fully
      understood. The clinical data show that neither soyfoods nor soy protein nor
      isoflavones affect circulating levels of reproductive hormones in men or women.
      However, some research suggests that soy protein, but not isoflavones, affects
      insulin-like growth factor I (IGF-1). METHODS: Since IGF-1 may have wide-ranging
      physiological effects, we sought to determine the effect of soy protein on IGF-1
      and its major binding protein insulin-like growth factor-binding protein (IGFBP
      3). Six clinical studies were identified that compared soy protein with a control
      protein, albeit only two studies measured IGFBP-3 in addition to IGF-1. RESULTS:
      Although the data are difficult to interpret because of the different
      experimental designs employed, there is some evidence that large amounts of soy
      protein (>25 g/day) modestly increase IGF-1 levels above levels observed with the
      control protein. CONCLUSION: The clinical data suggest that a decision to
      incorporate soy into the diet should not be based on its possible effects on IGF
      1.

PMID- 28434037
TI  - Open capsular and ligament reconstruction with semitendinosus hamstring autograft
      successfully controls superior and posterior translation for type V
      acromioclavicular joint dislocation.
AB  - PURPOSE: Appropriate surgical management for type V complete acromioclavicular
      (AC) joint dislocation remains controversial. The purpose of this paper is to
      retrospectively report the clinical and radiographic outcomes of an open surgical
      technique consisting for AC joint ligamentous and capsular reconstruction using
      autologous hamstring tendon grafts and semi-permanent sutures. METHODS: Between
      January 2005 and December 2011, 32 consecutive patients with symptomatic type V
      complete AC joint dislocation underwent surgical treatment using the same
      technique. The median time from injury to surgery was 45 days (range 24-90). The
      average median postoperative clinical and radiographic follow-up time was 30
      months (range 24-33). Clinical outcomes measures included the ASES score, the
      visual analog score (VAS), and subjective patient satisfaction score. Minimum
      follow-up was 2 years. RESULTS: ASES score increased from a median of 38.2 +/-
      6.2 preoperative to 92.1 +/- 4.7 postoperatively (p <= 0.05). The median VAS
      score improved from 62 mm (range 45-100 mm) preoperatively to 8 mm (range 0-20
      mm) at final follow-up (p <= 0.05). No patient experienced pain or discomfort
      with either direct palpation of the AC joint or with cross-body adduction. Final
      radiographs demonstrated symmetric AC joint contour in 25/32 (78%) patients.
      Seven patients (22%) radiographically demonstrated superior translation of the
      distal clavicle relative to the superior margin of the acromion but less than 50%
      of the clavicular width. 30/32 patients (93%) were able to return to their pre
      injury level of work and sports activities. CONCLUSIONS: This novel surgical
      technique using a free graft and braided suture for simultaneous coracoclavicular
      ligament and AC joint capsular reconstruction successfully controls superior and
      posterior translations after type V AC joint dislocation and minimizes the
      incidence of persistent postoperative AC joint subluxation. LEVEL OF EVIDENCE:
      Retrospective case series, Level IV.

PMID- 28434039
TI  - Outcome of stoma closure in babies with necrotising enterocolitis: early vs late
      closure.
AB  - : Newborns undergoing surgery for necrotizing enterocolitis (NEC) often require a
      stoma. Currently, there is no consensus regarding the best time for stoma closure
      (SC). Our aim was to determine the outcomes of early versus late closure.
      METHODS: Retrospective analysis of patients who underwent SC following stoma
      formation for NEC between Jan 2009 and July 2015 was done. Early (EC) versus late
      closure (LC) was defined as less than 10 weeks versus at or after 10 weeks of
      stoma formation. RESULTS: Of 36 patients, M:F was 23:13. Indications for
      laparotomy were pneumoperitoneum (30) and gangrene (6). Postoperatively, 9/15
      (60.0%) of EC group required ventilator support versus none in LC group (p <
      0.05). It took longer to establish full feeds following EC (12 days) versus LC (8
      days). Median duration of postoperative hospital stay following EC was 31 days
      (18-35) versus 7 days (4-54) following LC. Three patients were re-operated for
      intestinal obstruction (two following EC, one following LC). Three patients
      developed incisional hernia after EC versus none after LC (p < 0.05). One patient
      died after EC due to staphylococcus septicaemia. CONCLUSION: Early closure before
      10 weeks of formation for NEC patients is associated with significant morbidity,
      increased ventilator requirements and chances of developing incisional hernia.

PMID- 28434040
TI  - Primary ventral or groin hernia in pregnancy: a cohort study of 20,714 women.
AB  - BACKGROUND: Prevalence, management, and risk of emergency operation for primary
      ventral or groin hernia in pregnancy are unknown. The objective of this study was
      to estimate the prevalences of primary ventral or groin hernia in pregnancy and
      the potential risks for elective and emergency repair. METHODS: This single
      institutional retrospective study included all pregnant women attending one or
      more prenatal consultations at Hvidovre Hospital, Denmark, during a 3-year
      period. Patients' medical records were electronically retrieved. A free-text
      search algorithm and subsequent manual review was conducted to identify patients
      registered with a primary ventral or groin hernia in pregnancy. Follow-up was
      conducted by review of medical record notes within the Capital Region of Denmark
      supplemented with structured telephone interviews on indication. RESULTS: In
      total, 20,714 pregnant women were included in the study cohort. Seventeen (0.08%)
      and 25 (0.12%) women were registered with a primary ventral and groin hernia,
      respectively. None underwent elective or emergency repair in pregnancy, and all
      had uncomplicated childbirth. In 10 women, the groin bulge disappeared
      spontaneously after delivery. During postpartum follow-up of median 4.4 years
      (range 0.2-6.0 years), five (0.02%) and four (0.02%) underwent elective primary
      ventral and groin hernia repair, respectively. CONCLUSION: Primary ventral or
      groin hernia seems rare in pregnancy, and the incidence of emergency repair is
      extremely low. Watchful waiting strategy is recommended during pregnancy in women
      suspected for a primary ventral or groin hernia.

PMID- 28434041
TI  - Airway spray efficacy of local anesthetic with fiberscope.

PMID- 28434038
TI  - Emerging potential of gene silencing approaches targeting anti-chondrogenic
      factors for cell-based cartilage repair.
AB  - The field of cartilage repair has exponentially been growing over the past
      decade. Here, we discuss the possibility to achieve satisfactory regeneration of
      articular cartilage by means of human mesenchymal stem cells (hMSCs) depleted of
      anti-chondrogenic factors and implanted in the site of injury. Different types of
      molecules including transcription factors, transcriptional co-regulators,
      secreted proteins, and microRNAs have recently been identified as negative
      modulators of chondroprogenitor differentiation and chondrocyte function. We
      review the current knowledge about these molecules as potential targets for gene
      knockdown strategies using RNA interference (RNAi) tools that allow the specific
      suppression of gene function. The critical issues regarding the optimization of
      the gene silencing approach as well as the delivery strategies are discussed. We
      anticipate that further development of these techniques will lead to the
      generation of implantable hMSCs with enhanced potential to regenerate articular
      cartilage damaged by injury, disease, or aging.

PMID- 28434042
TI  - Erratum to: Curcumin induces G2/M arrest, apoptosis, NF-kappaB inhibition, and
      expression of differentiation genes in thyroid carcinoma cells.

PMID- 28434043
TI  - Early whole brain radiotherapy in primary CNS lymphoma: negative impact on
      quality of life in the randomized G-PCNSL-SG1 trial.
AB  - PURPOSE: In the randomized G-PCNSL-SG-1 trial, the addition of whole brain
      radiotherapy (45 Gy) to high-dose methotrexate (HD-MTX)-based chemotherapy (early
      WBRT arm) did not prolong overall survival (OS) as compared to HD-MTX-based
      chemotherapy alone (no early WBRT arm) in primary CNS lymphoma (PCNSL) patients.
      To determine whether WBRT might lead to quality of life (QoL)-relevant late
      neurotoxicity, this trial prospectively monitored QoL. METHODS: QoL measurements
      were performed using the EORTC-QLQ-C30 and BN20 questionnaires and combined with
      repeated Mini Mental State Examinations (MMSE). Exploratory data analysis
      included the 318 patients in the per-protocol population. RESULTS: In year 2
      after randomization, cognitive functioning and global health status were reduced
      in the early WBRT arm as compared to the no early WBRT arm (p = 0.004 and p =
      0.022, respectively). Also, fatigue (p = 0.037), appetite loss (p = 0.006) and
      hair loss (p = 0.002) were more intense in the early WBRT arm. MMSE testing
      revealed lower values (p = 0.002) in the early WBRT arm. A mixed model analysis
      of longitudinal data additionally showed differences favoring the no early WBRT
      arm in 15 of 26 dimensions of QoL. CONCLUSIONS: The analysis of subjective QoL
      questionnaires and objective MMSE testing revealed that QoL and cognition were
      conserved in the arm without early WBRT. Thus, even though it was an exploratory
      analysis, the results of G-PCNSL-SG1 challenge the place of WBRT in the primary
      therapy of PCNSL.

PMID- 28434045
TI  - Slow drilling speeds for single-drill implant bed preparation. Experimental in
      vitro study.
AB  - AIMS: To evaluate the real-time bone temperature changes during the preparation
      of the implant bed with a single-drill protocol with different drill designs and
      different slow drilling speeds in artificial type IV bone. MATERIALS AND METHODS:
      For this experimental in vitro study, 600 implant bed preparations were performed
      in 10 bovine bone disks using three test slow drilling speeds (50/150/300 rpm)
      and a control drilling speed (1200 rpm). The temperature at crestal and apical
      areas and time variations produced during drilling with three different drill
      designs with similar diameter and length but different geometry were recorded
      with real-life thermographic analysis. Statistical analysis was performed by two
      way analysis of variance. Multiple comparisons of temperatures and time with the
      different drill designs and speeds were performed with the Tukey's test. RESULTS:
      T Max values for the control drilling speed with all the drill designs (D1 +
      1200; D2 + 1200; D3 + 1200) were higher compared to those for the controls for 11
      +/- 1.32  degrees C (p < 0.05). The comparison of T Max within the test groups
      showed that drilling at 50 rpm resulted in the lowest temperature increment
      (22.11 +/- 0.8  degrees C) compared to the other slow drilling speeds of 150
      (24.752 +/- 1.1  degrees C) and 300 rpm (25.977 +/- 1.2  degrees C) (p < 0.042).
      Temperature behavior at crestal and apical areas was similar being lower for slow
      drilling speeds compared to that for the control drilling speed. Slow drilling
      speeds required significantly more time to finish the preparation of the implant
      bed shown as follows: 50 rpm > 150 rpm > 300 rpm > control (p < 0.05).
      CONCLUSIONS: A single-drill protocol with slow drilling speeds (50, 150, and 300
      rpm) without irrigation in type IV bone increases the temperature at the coronal
      and apical levels but is below the critical threshold of 47  degrees C. The drill
      design in single-drill protocols using slow speeds (50, 150, and 300 rpm) does
      not have an influence on the thermal variations. The time to accomplish the
      implant bed preparation with a single-drill protocol in type IV bone is
      influenced by the drilling speed and not by the drill design. As the speed
      decreases, then more time is required.

PMID- 28434046
TI  - Oral arginine supplementation protects female mice from the onset of non
      alcoholic steatohepatitis.
AB  - Dietary arginine (Arg) supplementation has been proposed to have positive effects
      on the development of liver diseases. In the present study, we investigate if an
      oral Arg supplementation in diet protects mice fed a fructose, fat and
      cholesterol enriched Western-style diet (WSD) from the development of non
      alcoholic steatohepatitis (NASH). Female C57BL/6J mice were fed a liquid control
      diet or a liquid WSD +/- Arg (2.49 g/kg body weight/day) for 6 weeks. Indices of
      liver injury, glucose metabolism and intestinal permeability were determined.
      While Arg supplementation had no effects on body weight gain, fasting blood
      glucose levels were significantly lower in WSD+Arg-fed mice than in C+Arg-fed
      animals. WSD-fed mice developed liver steatosis accompanied with inflammation,
      both being significantly attenuated in WSD+Arg-fed mice. These effects of Arg
      supplementation went along with a protection against WSD-induced decreased tight
      junction protein levels in the upper parts of the small intestine, increased
      levels of bacterial endotoxin in portal plasma as well as increased hepatic toll
      like receptor-4 mRNA and 4-hydroxynonenal protein adduct levels. In conclusion,
      Arg supplementation may protect mice from the development of NASH.

PMID- 28434044
TI  - Faulty RNA splicing: consequences and therapeutic opportunities in brain and
      muscle disorders.
AB  - Alternative splicing is a powerful mechanism that largely expands the coding
      potential of eukaryotic genomes. Indeed, its complex and flexible regulation is
      exploited by cells to adapt to various environmental conditions, through
      production of protein variants displaying different functions. Such flexibility,
      however, is accompanied by high risk of errors, and dysregulation of splicing is
      now recognized as an important factor in human diseases. Notably, the RNA-based
      nature of splicing, which involves high specificity through base pair
      recognition, offers a remarkable therapeutic opportunity by allowing design of
      tools with elevated target selectivity. Herein, we illustrate examples of how
      defective splicing, obtained by mutations affecting multiple layers of
      regulation, can result in pathology. In particular, we focus on splicing-related
      defects occurring in brain and muscle diseases and describe therapeutic
      approaches currently available for these pathologies.

PMID- 28434047
TI  - Late renal toxicity of treatment for childhood malignancy: risk factors, long
      term outcomes, and surveillance.
AB  - Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%,
      respectively, of children and adolescents treated with ifosfamide and 60-80% and
      10-30%, respectively, of those given cisplatin. Up to 20% of children display
      evidence of chronic glomerular damage after unilateral nephrectomy for a renal
      tumour. Overall, childhood cancer survivors have a ninefold higher risk of
      developing renal failure compared with their siblings. Such chronic
      nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy
      exposure to kidneys, renal surgery, supportive care drugs and tumour-related
      factors. These cause a wide range of chronic glomerular and tubular toxicities,
      often with potentially severe clinical sequelae. Many risk factors for developing
      nephrotoxicity, mostly patient and treatment related, have been described, but we
      remain unable to predict all episodes of renal damage. This implies that other
      factors may be involved, such as genetic polymorphisms influencing drug
      metabolism. Although our knowledge of the long-term outcomes of chronic
      nephrotoxicity is increasing, there is still much to learn, including how we can
      optimally predict or achieve early detection of nephrotoxicity. Greater
      understanding of the pathogenesis of nephrotoxicity is needed before its
      occurrence can be prevented.

PMID- 28434048
TI  - Clinical and radiological outcomes of endoscopic partial facetectomy for
      degenerative lumbar foraminal stenosis.
AB  - BACKGROUND: Several different techniques exist to treat degenerative lumbar
      foraminal stenosis. Failure to adequately decompress the lumbar foramen may lead
      to failed back surgery syndrome. However, wide decompression often causes spinal
      instabilities or may require an additional fusion surgery. The aim of this study
      was to report the outcomes of endoscopic partial facetectomy (EPF) performed on
      patients with degenerative lumbar foraminal stenosis. METHODS: Between 2012 and
      2014, 25 consecutive patients (12 women and 13 men) who underwent EPF were
      included in the study. The patients were assessed before surgery and followed-up
      regularly during outpatient visits (preoperatively and 1, 3, 6, 12, and 24 months
      postoperatively). The clinical outcomes were evaluated using the visual analog
      scale (VAS), Oswestry Disability Index (ODI), and Short Form-36 (SF-36) outcome
      questionnaire. The radiological outcome was measured using the lumbar Cobb angle,
      disc wedging angle, lumbar lordosis (LL), slip percentage, and disc height index
      (DHI) in plain standing radiographs. RESULTS: The VAS, ODI, and SF-36 scores
      significantly improved at 1 month of follow-up compared with the baseline mean
      values and were maintained within the 2-year follow-up period. There was no
      radiologic progression in the lumbar Cobb's angle, disc wedging angle, LL, slip
      percentage, and DHI between preoperatively and 2 years postoperatively. In
      addition, the EPF with discectomy group and the EPF group were not significantly
      different in terms of clinical and radiological outcomes. CONCLUSIONS: EPF is an
      effective option in decompressing the lumbar exiting nerve root without causing
      spinal instabilities for the treatment of patients with lumbar foraminal
      stenosis.

PMID- 28434049
TI  - A prospective study of the safety and efficacy of a combined bipolar
      radiofrequency, intense pulsed light, and infrared diode laser treatment for
      global facial photoaging.
AB  - The clinical features of photoaging include: skin texture changes, laxity,
      rhytides, pigmentary changes, and vascular changes such as erythema and
      telangiectasias. In order to meet patients' increasing demands for improving all
      aspects of photoaging at one office visit, employing a multi-modality treatment
      for all aspects of photoaging has become increasingly desirable for the physician
      and patient alike. We examine a novel device that employs bipolar radiofrequency
      (RF), intense pulsed light (IPL), and infrared diode laser. These laser and light
      source treatments are performed sequentially. This study aims to evaluate the
      clinical efficacy and safety of this device (i.e., ELOS TrinitiTM). Twenty-six
      subjects received four ELOS TrinitiTM treatments at 1-month intervals. They were
      followed up 1, 3, and 6 months after completing the treatments. Two blinded
      dermatologists used a comprehensive grading scale to evaluate the degree of the
      photoaging in terms of rhytides, laxity, dyschromia, erythema, telangiectasias,
      and texture. Subjects used a 0-10 grading scale for self-assessment of
      photoaging. Additionally, we measured the Erythema Index (EI), Melanin Index
      (MI), transepidermal water loss scores (TEWL), stratum corneum moisture scores
      (SC), and dermis moisture scores (D) before treatment and 1, 3, and 6 months
      after treatment. There was a statistically significant improvement in all five
      aspects of the comprehensive grading scale. Overall, it had excellent efficacy
      for improving erythema, telangiectasias, and skin texture. It also had a
      relatively long effect on improving skin laxity; however, it had only a limited
      ability to improve rhytides and dyschromia. It can mildly to moderately improve
      the global photoaging. This global effect can be noted 1 month after treatment
      and becomes most clinically apparent 3 months after treatment. This is maintained
      at least 6 months after treatment. MI index and SC and D values increased while
      EI index and TEWL values decreased after the treatment. The subjects' self
      assessment improved by 2.7 +/- 1.2 points. The overall satisfaction rate was 88%.
      The degree of pain measured 2.5 +/- 1.9 points on average. There was no downtime
      and no severe side effects reported. The sequential implementation of bipolar
      radiofrequency based optical combination devices (IPL, IR, diode laser) is
      effective and safe for global facial photoaging.

PMID- 28434050
TI  - Prevalence of Toxoplasma gondii infection in HIV-infected patients and food
      animals and direct genotyping of T. gondii isolates, Southern Ghana.
AB  - Toxoplasma gondii is of public health and veterinary importance causing severe
      diseases in immunocompromised individuals including HIV/AIDS patients and in
      congenital cases and animals. There is limited information on the epidemiology of
      T. gondii infection in humans, particularly HIV patients and food animals and the
      parasite genotypes in Ghana. A total of 394 HIV-infected patients from three
      hospitals were screened for T. gondii anti-IgG and IgM using ELISA. DNAs from
      blood samples of seropositve participants and 95 brain tissues of food animals
      were PCR assayed to detect Toxoplasma gra6. DNA positive samples were genotyped
      using multilocus nested polymerase chain reaction restriction fragment length
      polymorphism at 10 loci: sag1, alt.sag2, sag3, btub, gra6, l358, c22-8, c29-2,
      pk1, and apico. The overall seroprevalence was 74.37% (293/394). Toxoplasma DNAs
      were detected in 3.07% of the seropositive participants and 9.47% of the animals.
      Six of the human DNA positive samples were partly typed at sag3: 33.33, 50, and
      16.67% isolates had type I, II, and III alleles, respectively. All nine isolates
      from food animals typed at nine loci except apico were atypical: six isolates
      were identical to ToxoDB #41 and #145, and one was identical to TgCkBrRj2 all
      identified in Brazil. The genotype of two isolates has not been reported
      previously and was named as TgCtGh1. T. gondii seroprevalence is high among the
      HIV-infected individuals with T. gondii circulating in Ghana being genetically
      diverse.

PMID- 28434051
TI  - Evidence of a link between fever and microscopic hematuria in children.
AB  - : Despite the common conception that febrile illnesses are associated with
      microscopic hematuria in children, a review of the literature failed to disclose
      supportive evidence. The aim of this study was to evaluate this relationship.
      Background data were collected for a convenience sample of children aged 4-18
      years who presented to the emergency department (ED) of a tertiary pediatric
      medical center. Vital signs were measured and a midstream urine specimen was
      collected. Specimens positive for the presence of blood (>5 erythrocytes/MUl;
      Combur 10 Test Strips) were examined microscopically. Patients found to have
      microscopic hematuria (>5 erythrocytes/high power field) were asked to undergo
      repeated urine testing within 3 weeks or at least 1 week after the fever (if
      present) resolved. A telephone interview was conducted 9-10 years after the ED
      visit, for all children with microscopic hematuria. Data were coded and
      transferred to Microsoft Excel 2007 (Raymond Wa), and then analyzed using SPSS 15
      (SPSS Inc., Chicago, IL). Six hundred sixty patients were enrolled in the study;
      161 were febrile (mean temperature 39.2 +/- .08  degrees C), and 499 were
      afebrile (mean temperature 36.7 +/- 0.4  degrees C) (p < 0.001). The febrile
      group was significantly younger than the afebrile group (mean age 8 +/- 3.6 years
      versus 9.4 +/- 3.7 years, respectively, p < 0.001). There was no significant
      between-group difference in sex distribution (55 and 60% boys, respectively, p =
      0.199). Microscopic hematuria was found in 12 children, 9 febrile (5.6%), and 3
      afebrile (0.6%) (p < 0.001). All repeated urine tests (n = 12) were negative for
      microscopic hematuria. CONCLUSION: The findings suggest that fever is associated
      with transient microscopic hematuria in children. The study is limited by its
      single-center setting and relatively small sample. What is known: * It is
      commonly believed that fever increases the incidence of microscopic hematuria. *
      However, to the best of our knowledge, this assumption has not been proven. What
      is new: * This study demonstrates a significant association between fever and
      transient microscopic hematuria in children. * The transient nature of the
      hematuria may be reassuring for both parents and healthcare providers.

PMID- 28434052
TI  - Core curriculum illustration: orbital blow out fracture.
AB  - This is the 32nd installment of a series that will highlight one case per
      publication issue from the bank of cases available online as part of the American
      Society of Emergency Radiology (ASER) educational resources. Our goal is to
      generate more interest in and use of our online materials. To view more cases
      online, please visit the ASER Core Curriculum and Recommendations for Study
      online at: http://www.erad.org/page/CCIP_TOC.

PMID- 28434053
TI  - Chinese Beliefs in Luck are Linked to Gambling Problems via Strengthened
      Cognitive Biases: A Mediation Test.
AB  - Problematic patterns of gambling and their harms are known to have culturally
      specific expressions. For ethnic Chinese people, patterns of superstitious belief
      in this community appear to be linked to the elevated rates of gambling-related
      harms; however, little is known about the mediating psychological mechanisms. To
      address this issue, we surveyed 333 Chinese gamblers residing internationally and
      used a mediation analysis to explore how gambling-related cognitive biases,
      gambling frequency and variety of gambling forms ('scope') mediate the
      association between beliefs in luck and gambling problems. We found that
      cognitive biases and scope were significant mediators of this link but that the
      former is a stronger mediator than the latter. The mediating erroneous beliefs
      were not specific to any particular type of cognitive bias. These results suggest
      that Chinese beliefs in luck are expressed as gambling cognitive biases that
      increase the likelihood of gambling problems, and that biases that promote
      gambling (and its harms) are best understood within their socio-cultural context.

PMID- 28434054
TI  - Patterns of Gambling Activities and Gambling Problems Among Italian High School
      Students: Results from a Latent Class Analysis.
AB  - This study aims to provide an estimate of the prevalence of gambling among
      Italian adolescents and a description of their patterns of gambling activities
      (PGAs) using a latent class analysis on 13 different types of games. A nationwide
      sample of 10,959 Italian high school students was recruited in 2013. We assessed
      problem gambling using the South Oaks Gambling Screen: Revisited for Adolescent
      (SOGS-RA) scale. Approximately half (50.6%) of students reported gambling at
      least once in the previous year; 5.0% of them were problem gamblers and 9.1% were
      at-risk gamblers according to their SOGS-RA scores. Eight PGAs were identified,
      among which heavy players (1.7% of students) could be classified as problem
      gamblers and broad skill players (2.0%) and lotteries & sports players (2.4%) as
      "at-risk" players. These high-risk classes were consistently associated with
      risky behaviours in terms of substance use, school performance, money spent on
      gambling and family environment; the other five classes identified low-risk
      players associated with safe behaviours. To the best of our knowledge, this is
      the first study to identify PGAs among Italian adolescents. Problem gamblers are
      not a homogeneous group in terms of patterns of gambling activities and are
      associated with different risk factors, among which environmental factors, such
      as parents' gambling attitude and behaviour, deserve special attention. The
      acknowledgment of such patterns and risk factors could be useful in developing
      sensible public policies addressing prevention strategies and regulatory
      instruments.

PMID- 28434056
TI  - Beyond the Primary Endpoint Paradigm: A Test of Intervention Effect in HIV
      Behavioral Intervention Trials with Numerous Correlated Outcomes.
AB  - Behavioral interventions are increasingly based on holistic approaches to health
      with an understanding that health-related behaviors are linked. A motivating
      example is provided by the Philani study, an intervention trial conducted to
      improve the health of South African mothers and their children. Inter-related
      health problems around maternal alcohol use, malnutrition, and HIV were
      addressed; multiple endpoints were targeted. The traditional hypothesis testing
      paradigm that tests significance on one primary outcome did not suffice. Past
      multiple endpoint studies have utilized a sign test on the number of estimated
      differences between treatment and control that favor the intervention. However,
      in order to preserve type 1 error, one must account for correlations among the
      outcomes. We propose an alternative approach that counts the number of
      significant treatment-control differences. Monte Carlo simulation is used to
      adjust for correlation, providing updated critical values and p values. Our
      method is implemented through an R package and applied to the Philani data to
      test the intervention's overall effect.

PMID- 28434057
TI  - Predictive control of intersegmental tarsal movements in an insect.
AB  - In many animals intersegmental reflexes are important for postural and movement
      control but are still poorly undesrtood. Mathematical methods can be used to
      model the responses to stimulation, and thus go beyond a simple description of
      responses to specific inputs. Here we analyse an intersegmental reflex of the
      foot (tarsus) of the locust hind leg, which raises the tarsus when the tibia is
      flexed and depresses it when the tibia is extended. A novel method is described
      to measure and quantify the intersegmental responses of the tarsus to a stimulus
      to the femoro-tibial chordotonal organ. An Artificial Neural Network, the Time
      Delay Neural Network, was applied to understand the properties and dynamics of
      the reflex responses. The aim of this study was twofold: first to develop an
      accurate method to record and analyse the movement of an appendage and second, to
      apply methods to model the responses using Artificial Neural Networks. The
      results show that Artificial Neural Networks provide accurate predictions of
      tarsal movement when trained with an average reflex response to Gaussian White
      Noise stimulation compared to linear models. Furthermore, the Artificial Neural
      Network model can predict the individual responses of each animal and responses
      to others inputs such as a sinusoid. A detailed understanding of such a reflex
      response could be included in the design of orthoses or functional electrical
      stimulation treatments to improve walking in patients with neurological disorders
      as well as the bio/inspired design of robots.

PMID- 28434055
TI  - Addressing Methodologic Challenges and Minimizing Threats to Validity in
      Synthesizing Findings from Individual-Level Data Across Longitudinal Randomized
      Trials.
AB  - Integrative Data Analysis (IDA) encompasses a collection of methods for data
      synthesis that pools participant-level data across multiple studies. Compared
      with single-study analyses, IDA provides larger sample sizes, better
      representation of participant characteristics, and often increased statistical
      power. Many of the methods currently available for IDA have focused on examining
      developmental changes using longitudinal observational studies employing
      different measures across time and study. However, IDA can also be useful in
      synthesizing across multiple randomized clinical trials to improve our
      understanding of the comprehensive effectiveness of interventions, as well as
      mediators and moderators of those effects. The pooling of data from randomized
      clinical trials presents a number of methodological challenges, and we discuss
      ways to examine potential threats to internal and external validity. Using as an
      illustration a synthesis of 19 randomized clinical trials on the prevention of
      adolescent depression, we articulate IDA methods that can be used to minimize
      threats to internal validity, including (1) heterogeneity in the outcome measures
      across trials, (2) heterogeneity in the follow-up assessments across trials, (3)
      heterogeneity in the sample characteristics across trials, (4) heterogeneity in
      the comparison conditions across trials, and (5) heterogeneity in the impact
      trajectories. We also demonstrate a technique for minimizing threats to external
      validity in synthesis analysis that may result from non-availability of some
      trial datasets. The proposed methods rely heavily on latent variable modeling
      extensions of the latent growth curve model, as well as missing data procedures.
      The goal is to provide strategies for researchers considering IDA.

PMID- 28434058
TI  - Medical Conditions in the First Years of Life Associated with Future Diagnosis of
      ASD in Children.
AB  - This study examines medical conditions diagnosed prior to the diagnosis of autism
      spectrum disorder (ASD). Using a matched case control design with 3911 ASD cases
      and 38,609 controls, we found that 38 out of 79 medical conditions were
      associated with increased ASD risk. Developmental delay, mental health, and
      neurology conditions had the strongest associations (ORs 2.0-23.3). Moderately
      strong associations were observed for nutrition, genetic, ear nose and throat,
      and sleep conditions (ORs 2.1-3.2). Using machine learning methods, we clustered
      children based on their medical conditions prior to ASD diagnosis and
      demonstrated ASD risk stratification. Our findings provide new evidence
      indicating that children with ASD have a disproportionate burden of certain
      medical conditions preceding ASD diagnosis.

PMID- 28434060
TI  - Erratum to: The patient-reported outcome content of international ovarian cancer
      randomised controlled trial protocols.

PMID- 28434059
TI  - Early warning score independently predicts adverse outcome and mortality in
      patients with acute pancreatitis.
AB  - PURPOSE: The aim of this study was to compare the prognostic value of established
      scoring systems with early warning scores in a large cohort of patients with
      acute pancreatitis. METHODS: In patients presenting with acute pancreatitis, age,
      sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score,
      Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for
      the first 72 h following admission. These variables were compared between
      survivors and non-survivors, between patients with mild/moderate and severe
      pancreatitis (based on the 2012 Atlanta Classification) and between patients with
      a favourable or adverse outcome. RESULTS: A total of 629 patients were
      identified. EWS was the best predictor of adverse outcome amongst all of the
      assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1,
      2 and 3, respectively) and was the most accurate predictor of mortality on both
      days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis
      revealed that an EWS >=2 was independently associated with severity of
      pancreatitis, adverse outcome and mortality. CONCLUSION: This study confirms the
      usefulness of EWS in predicting the outcome of acute pancreatitis. It should
      become the mainstay of risk stratification in patients with acute pancreatitis.

PMID- 28434061
TI  - The sources of calcium for noradrenaline-induced contraction in the human
      thoracic internal artery.
AB  - The aim of the present study was to examine the contribution of intracellular and
      extracellular calcium sources in contraction caused by noradrenaline (NA) of the
      human internal thoracic artery (ITA) in vitro. Distal segments of ITA were
      obtained from 20 patients (aged 38-73, at the time of routine coronary artery
      surgical revascularization (CABG)). Contractile responses to 10-6 mol/L NA in the
      physiological salt solution and in Ca2+-free solution without and after
      incubation with 10-6 mol/L thapsigargin (TSG) were recorded under isometric
      conditions. Responses of ITA rings to 1 MUM NA without incubation with TSG
      accounted (% of reaction to 80 mM KCl) 224.70 +/- 14.06% in PSS solution, 141.30
      +/- 8.66% in Ca2+-free solution, and 80.03 +/- 1.71% after PSS restoration and
      were statistically significantly different (p < 0.0001, one-way ANOVA). Responses
      of ITA rings to 1 MUM NA with 1 MUM TSG accounted (% of reaction to 80 mM KCl)
      114.50 +/- 2.79% in Ca2+-free solution and 36.70 +/- 2.38% after PSS restoration.
      Responses in Ca2+-free solution and after PSS restoration without and with TSG
      were statistically significantly different (p = 0.0257 and p < 0.0001,
      respectively-t test). ITA contraction is caused by calcium derived not only from
      the SR and the extracellular matrix. The delivery of calcium to the space
      surrounding tissue does not immediately deliver calcium to the myofilaments.

PMID- 28434062
TI  - NLOphoric 3,6-di(substituted quinoxalin) Carbazoles - Synthesis, Photophysical
      Properties and DFT Studies.
AB  - Synthesis of novel 3,6-di(substituted quinoxalin) carbazole fluorophores by the
      condensation of 1,1'-(9-ethyl-9H-carbazole-3,6-diyl)bis(2-bromoethanone) with
      methyl, chloro and unsubstituted o-phenylenediamine is presented. Synthesized
      derivatives are well characterized by 1H NMR, 13C NMR, FTIR and Mass
      spectroscopy. Photophysical studies are carried out using solvents of varying
      polarities revealed positive solvatochromism and intramolecular charge transfer
      from carbazole (Donor) to quinoxalin (Acceptor). Intramolecular charge transfer
      properties are correlated by dipole moment changes and different polarity
      functions like Lippert-Mataga, Bilot-Kawski, Bakhshiev and Liptay plots with very
      good regression factors. Mulliken hush-analysis further support charge transfer
      characteristic. Linear and Nonlinear optical properties are explained by
      solvatochromic data using two-level quantum mechanical model and are correlated
      with computational calculations using density functional theory at B3LYP/6-31G(d)
      level. First hyperpolarizability value of all the synthesized compounds is found
      to be greater than urea by >333 times. Moreover, increase of hyperpolarizability
      values from non-polar to polar solvents are in good correlation with the
      significant charge transfer characteristic in polar solvents.

PMID- 28434063
TI  - Constrained Photophysics of 5,7-dimethoxy-2,3,4,9-tetrahydro-1H-carbazol-1-one in
      the Bioenvironment of Serum Albumins: A Spectroscopic Endeavour Supported by
      Molecular Docking Analysis.
AB  - This paper vividly indicates that steady state as well as time-resolved
      fluorescence techniques can serve as highly sensitive monitors to explore the
      interactions of 5,7-dimethoxy-2,3,4,9-tetrahydro-1H-carbazol-1-one with model
      transport proteins, bovine serum albumin (BSA) and human serum albumin (HSA).
      Besides these, we have used fluorescence anisotropy study to assess the degree of
      restrictions imparted by the micro-environments of serum albumins. Again, to
      speculate the triplet excited state interaction between such fluorophore and
      albumin proteins (BSA& HSA), laser flash-photolysis experiments have been carried
      out. Molecular docking experiments have also been performed to support the
      conclusions obtained from steady state experiments.

PMID- 28434064
TI  - The utility of CT and MRI in detecting male urethral recurrence after radical
      cystectomy.
AB  - PURPOSE: To evaluate the utility of computed tomography (CT) and magnetic
      resonance imaging (MRI) in detecting male urethral recurrence (UR). MATERIALS AND
      METHODS: Between December 2008 and March 2016, 12 men (age range 61-85 years;
      median, 74 years) with urethral bloody discharge or pain were histologically
      confirmed as UR after radical cystectomy due to urothelial carcinoma. Of these
      patients, eight underwent both CT and MRI. The remaining four patients underwent
      CT only. CT and MRI were compared regarding UR detection rate. CT and MRI were
      also evaluated to determine which modality was more accurate for depicting UR. UR
      detection rate of each MRI sequence were recorded. Standard reference was biopsy
      or urethrectomy in 11 patients and size change in one patient after treatment.
      RESULTS: UR detection rate with CT was 41.7% (5/12), while that with MRI was 100%
      (8/8) (p = 0.0147). Of the eight patients who were diagnosed UR with MRI, six
      were detected with MRI alone and two with both MRI and CT (p = 0.0313). UR
      detection rates of T2-weighted, T1-weighted, diffusion-weighted, and contrast
      enhanced MRI were 87.5% (7/8), 62.5% (5/8), 100% (5/5), and 87.5% (7/8),
      respectively. CONCLUSION: MRI is superior to CT in detecting male URs in
      symptomatic patients after radical cystectomy. T2-weighted, diffusion-weighted,
      and contrast-enhanced MRI sequences are useful for detecting male UR.

PMID- 28434065
TI  - Alternative reverse genetics system for influenza viruses based on a synthesized
      swine 45S rRNA promoter.
AB  - We generated an alternative reverse genetics (RG) system based on a synthesized
      swine 45S rRNA promoter to rescue the H3N2 subtype swine influenza virus. All
      eight flanking segment cassettes of A/swine/Henan/7/2010 (H3N2) were amplified
      with ambisense expression elements from RG plasmids. All segments were then
      recombined with the pHC2014 vector, which contained the synthesized swine 45S
      rRNA promoter (spol1) and its terminal sequence (t1) in a pcDNA3 backbone. As a
      result, we obtained a set of RG plasmids carrying the corresponding eight-segment
      cassettes. We efficiently generated the H3N2 virus after transfection into
      293T/PK15, PK15, and 293T cells. The efficiency of spol1-driven influenza virus
      rescue in PK15 cells was similar to that in 293T cells by titration using the
      human pol1 RG system. Our approach suggests that an alternative spol1-based RG
      system can produce influenza viruses.

PMID- 28434066
TI  - Toxicity and Genotoxicity of Three Antimicrobials Commonly Used in Veterinary
      Medicine.
AB  - The toxicity of chlortetracycline (CTC), oxytetracycline (OTC) and enrofloxacin
      (ENF) was tested on two green algal species: the international standard
      Pseudokirchneriella subcapitata and the native Argentine species Ankistrodesmus
      fusiformis. All three antibiotics inhibited the algal growth. The most sensitive
      species was P. subcapitata, for which the EC50 for CTC, OTC and ENF were 1.19 +/-
      0.53, 0.92 +/- 0.30 and 5.18 +/- 3.80 mg L-1, respectively. The EC50 for A.
      fusiformis, were 3.23 +/- 0.53, 7.15 +/- 2.69 and 10.6 +/- 1.28 mg L-1,
      respectively. The genotoxicity of these veterinary antibiotics was also assessed
      using chromosome aberration (CA) and micronuclei (MN) induction in Allium cepa
      roots. Three concentrations were tested (0.1, 1 and 10 mg L-1). Only ENF at 1 and
      10 mg L-1 showed any significant MN induction. These data revealed that CTC, OTC
      and ENF could cause toxicity on green algae, whereas ENF could cause genotoxicity
      on A. cepa plants.

PMID- 28434067
TI  - Sediment Metal Contamination in the Kafue River of Zambia and Ecological Risk
      Assessment.
AB  - Zambia's Kafue River receives wastes from various sources, resulting in metal
      pollution. This study determined the degree of contamination of 13 metals (Al,
      Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Hg and Pb) in Kafue River sediment and
      the associated ecological risks at six sites in three different seasons. The
      level of contamination for most metals showed significant site and seasonal
      differences. The contamination factor and pollution load index indicated that
      concentrations of most metals particularly copper (Cu), cobalt (Co), manganese
      (Mn) and arsenic (As) were very high at sites within the Copperbelt mining area.
      The geoaccumulation index showed an absence of anthropogenic enrichment with Cd
      and Hg at all the study sites and extreme anthropogenic enrichment with Cu at
      sites in the Copperbelt mining area. Potential ecological risk showed that Cu and
      As were likely to cause adverse biological effects to aquatic organisms in the
      Copperbelt mining region of the Kafue River.

PMID- 28434068
TI  - Assessment of DDT and Metabolites in Soil and Sediment of Potentially
      Contaminated Areas of Belem, Amazon Region, Brazil.
AB  - The aim of this study was to evaluate the distribution of DDT and metabolites in
      surface soils and soil profiles from two areas containing deposits of obsolete
      pesticides in Belem, Amazon Region, Brazil. DDT and metabolites were extracted by
      microwave assisted extraction and analyzed by gas chromatography with electron
      capture detection. Concentrations of total DDT in surface soil samples ranged
      from 64.22 mg kg-1 in area 1 (A1) to 447.84 mg kg-1 in area 2 (A2). Lower levels
      were found in soil profiles than at the surface (6.21-21.17 mg kg-1 in A1 and
      36.13-113.66 mg kg-1 in A2). pp'-DDT, pp'-DDE and pp'-DDD were detected in
      sediments at levels of 2.01, 0.96 and 0.35 mg kg-1, respectively. The ratio (DDE
      + DDD)/SigmaDDT was low indicating the recent introduction of DDT to the
      environment in the two study areas, through the volatilization and atmospheric
      deposition of the obsolete pesticides.

PMID- 28434069
TI  - Herpes zoster keratitis development after acute retinal necrosis.
AB  - PURPOSE: To report a case of herpes zoster keratitis in a patient undergoing
      treatment for herpetic acute retinal necrosis. METHODS: Case report. RESULTS: A
      71 year old male presented with acute retinal necrosis of the left eye due to
      herpes zoster and was treated with intravitreal foscarnet and oral valcyclovir.
      He developed a retinal detachment and underwent surgical repair. After four
      weeks, he developed an ipsilateral herpetic zoster keratitis demonstrated by Rose
      Bengal staining that was responsive to topical ganciclovir gel. CONCLUSIONS: This
      case report describes the unusual development of herpes zoster keratitis after
      the development of unilateral acute retinal necrosis (ARN) in a patient on
      antiviral treatment.

PMID- 28434070
TI  - Subconjunctival hemorrhage and vision loss after regional ocular anesthesia.
AB  - PURPOSE: To report two cases of retinal vascular occlusion and associated
      subconjunctival hemorrhage in needle optic nerve injury during local bulbar
      anesthesia. METHODS: Surgical records of these two subjects who presented with
      acute vision loss after cataract extraction were studied, and systemic workup and
      ocular imaging were carried out to establish the cause. RESULTS: Computerized
      tomography showed evidence of optic nerve injury. CONCLUSION: Subconjunctival
      hemorrhage could be an associated clinical finding in hypodermic needle injury
      related retinal vascular occlusion during ocular anesthesia.

PMID- 28434071
TI  - Repeatability and agreement of central corneal thickness measurement with non
      contact methods: a comparative study.
AB  - PURPOSE: To compare the central corneal thickness (CCT) measurements and
      reliability of RTVue XR-100 anterior segment optical coherence tomography (AS
      OCT), AL-scan optical biometer and Schwind Sirius anterior segment analysis
      system. METHODS: The CCT was measured in one hundred and twenty-seven eyes of 127
      healthy subjects with AS-OCT, AL-scan and Sirius system. Mean CCT was compared
      among the instruments, and the level of agreement was assessed using Bland-Altman
      plots. One eye each of 30 subjects was randomly assigned for intrasession
      intraoperator and interoperator repeatability which was assessed using
      coefficient of variation and intraclass correlation coefficient. RESULTS: Mean
      CCT with AS-OCT, AL-scan and Sirius system was 496.72 +/- 32.75, 507.43 +/- 33.54
      and 512.08 +/- 33.1 um, respectively. There was no statistically significant
      difference between AL-scan and Sirius system (p = 0.26). Significant difference
      was found between AS-OCT/AL-scan (p = 0.01) and AS-OCT/Sirius system (p <
      0.0001). Bland-Altman analysis showed a high level of agreement between AL
      Scan/Sirius system (Mean difference -4.6 um) and a low level of agreement between
      AS-OCT/AL-scan (Mean difference -10.7 um) and OCT/Sirius system (Mean difference 
      15.4 um). CONCLUSIONS: AS-OCT underestimated CCT measurements when compared to
      other two devices in healthy subjects. Hence, one must be cautious when analyzing
      the results from different machines and should be aware that the measurement
      values are not interchangeable.

PMID- 28434072
TI  - Risk factors for childhood obesity: Do the birth weight, type of delivery, and
      mother's overweight have an implication on current weight status?
AB  - BACKGROUND: The aim of this study was to identify risk factors, including the
      type of delivery, breastfeeding and its duration, birth weight, the timing of
      solid food introduction, the mother's education level at birth, and smoking
      status during pregnancy, that are associated with obesity in children living in
      Istanbul. METHODS: This study involving 4990 healthy children aged 2-14 years, at
      an outpatient clinic in a tertiary care hospital from June 2012 to July 2014.
      RESULTS: The overall rates of overweight and obesity in children were 13.1% and
      7.8%, respectively. Results demonstrated that 44.5% of children were delivered by
      caesarean section. In all age groups, 7.8% of children delivered by caesarean
      section were obese compared with 7.9% of children born vaginally. No significant
      association between caesarean section delivery and obesity in childhood was found
      in our study [odds ratio (OR)=0.98, 95% confidence interval (CI)=0.64-2.87,
      P=0.454]. There was also no association between duration of breastfeeding and the
      introduction of solid foods before 4 months or after 6 months of age and
      childhood obesity (OR=0.95, 95% CI=0.69-1.3, P=0.771; OR=0.99, 95% CI=0.64-1.53,
      P=0.261). Regression analyses revealed that children with birth weights greater
      than 3801 g or those with maternal body mass index (BMI) equal to or greater than
      30 had an increased risk of being obese or overweight (OR=1.78, 95% CI=1.19-2.65;
      OR=3.95, 95% CI=1.94-5.81). CONCLUSIONS: This study demonstrated that increased
      birth weight and maternal BMI are significant risk factors for obesity in
      children living in Istanbul, Turkey. No relation between caesarean section
      delivery and childhood obesity was found in this study.

PMID- 28434073
TI  - Direct Downregulation of B-Cell Translocation Gene 3 by microRNA-93 Is Required
      for Desensitizing Esophageal Cancer to Radiotherapy.
AB  - BACKGROUND: Esophageal squamous carcinoma (ESC) is one of the most fatal
      malignancies worldwide with increasing occurrences yet poor outcome. MicroRNAs
      were reported to play roles in ESC. AIMS: We aimed to understand how miRNAs
      affect the radiotherapy resistance of ESC. METHODS: MicroRNA assays, real-time
      PCR, and Western blot were performed for expression analysis of miR-93 and BTG3.
      Luciferase activity assay was conducted with mutated B-cell translocation gene 3
      (BTG3) 3'-UTR sequence in the 3' end of luciferase sequence with miR-93
      inhibitor. ESC cells were treated with irradiation (IR) and clonogenic assay was
      utilized to detect the cell viability. Human ESC xenograft mouse model was
      established and subjected to target IR treatment followed by tumor size analysis.
      RESULTS: MiR-93 was decreased and BTG3 was increased in ESC cells, with negative
      correlation of their expression in ESC tissues. MiR-93 directly targeted BTG3 3'
      UTR by luciferase activity assay. Either miR-93 inhibition or BTG3 overexpression
      decreased radiation resistance. Furthermore, miR-93 inhibition suppressed
      radiation resistance through BTG3. CONCLUSIONS: Direct downregulation of BTG3 by
      miR-93 is able to render ESC resistant to radiotherapy, and both BTG3 and miR-93
      may potentially serve as clinical markers for ESC and contribute to the treatment
      of ESC.

PMID- 28434074
TI  - Adipose-Derived Stem Cells Ameliorate Experimental Murine Colitis via TSP-1
      Dependent Activation of Latent TGF-beta.
AB  - BACKGROUND: Adipose tissue-derived stem cells (ASCs) have been investigated as
      therapeutic tools for a variety of autoimmune diseases, including inflammatory
      diseases. However, the mechanisms underlying the immunomodulatory properties of
      ASCs are not well understood. Here, we investigated the mechanism of regulatory T
      cell (Treg) induction in ASC therapy in a murine model of inflammatory bowel
      disease. METHODS: Acute colitis was induced in mice using dextran sulfate sodium
      and ASCs administered intraperitoneally. Tregs and CD103+ dendritic cells were
      analyzed in the mesenteric lymph nodes (MLNs), spleen, and colonic lamina propria
      (CLP). Activation of latent TGF-beta by ASCs was analyzed in vitro using ELISA.
      siRNA technology was used to create ASCs in which TSP-1 or integrinalphav was
      knocked down in order to investigate the involvement of these proteins in the
      activation of latent TGF-beta. In addition, TSP-1-knockdown ASCs were
      administered to mice with colitis to assess their clinical efficacy in vivo.
      RESULTS: Systemic administration of ASCs significantly lessened the clinical and
      histopathological severity of colitis. ASCs were distributed throughout the
      lymphatic system in the MLNs and spleen. Tregs were increased in the MLNs and
      CLP, but CD103+ dendritic cells were not significantly altered. The ASCs
      activated latent TGF-beta. TSP-1 knockdown impaired TGF-beta activation in vitro
      and abrogated the therapeutic effects of the ASCs in vivo. Furthermore, Tregs
      were not increased in the MLNs and CLP from mice treated with TSP-1-knockdown
      ASCs. CONCLUSIONS: These results demonstrate that ASCs induce Tregs by activating
      latent TGF-beta via TSP-1, independent of CD103+ dendritic cell induction.

PMID- 28434075
TI  - Associations of self-reported smoking, cotinine levels and epigenetic smoking
      indicators with oxidative stress among older adults: a population-based study.
AB  - Tobacco smoking and oxidative stress (OS) are both related to a wide spectrum of
      adverse age-related health outcomes, but their association is not yet well
      established. We examined the associations of self-reported smoking indicators,
      serum cotinine levels and smoking-related DNA methylation biomarkers with two
      urinary proxy markers of OS, 8-isoprostane (8-iso) and 8-hydroxy-2'
      deoxyguanosine (8-oxodG), in two independent subsets of older adults recruited in
      Germany (discovery set: n = 978, validation set: n = 531). We obtained DNA
      methylation profiles in whole blood samples by Illumina Human Methylation450K
      Beadchip and measured the urinary levels of both OS markers using commercial
      ELISA kits. After controlling for potential confounders, current smoking,
      cumulative smoking exposure (pack-years) and serum cotinine levels (ng/ml) were
      strongly associated with 8-iso levels (p values <0.0001, 0.004 and 0.001,
      respectively). Of 151 previously identified smoking-related CpG sites, 71 loci
      were associated with 8-iso levels after correction for multiple testing (FDR <
      0.05) in the validation phase and were designated as loci related to 8-iso levels
      defined OS. In addition, serum cotinine levels, cumulative smoking exposure and a
      smoking index (SI) based on the 71 identified loci manifested monotonic
      associations with 8-iso levels. However, we did not observe any associations
      between these smoking indicators and 8-oxodG levels. In conclusion, this study
      suggests that smoking-related epigenetic alterations are closely correlated with
      smoking-induced OS. The identified CpG sites could potentially be prognostic
      epigenetic markers of OS and OS-related health outcomes. Our findings and the
      underlying mechanisms should be followed up in further, preferably longitudinal
      studies.

PMID- 28434076
TI  - alpha-Synuclein nonhuman primate models of Parkinson's disease.
AB  - Proper understanding of the mechanism(s) by which alpha-synuclein misfolds and
      propagates may hold the key to unraveling the complex pathophysiology of
      Parkinson's disease. A more complete understanding of the disease itself, as well
      as establishing animal models that fully recapitulate pathological and functional
      disease progression, are needed to develop treatments that will delay, halt or
      reverse the disease course. Traditional neurotoxin-based animal models fail to
      mimic crucial aspects of Parkinson's and thus are not relevant for the study of
      neuroprotection and disease-modifying therapies. Therefore, a new era of animal
      models centered on alpha-synuclein has emerged with the utility of nonhuman
      primates in these studies beginning to become important. Indeed, disease modeling
      in nonhuman primates offers a more similar anatomical and genetic background to
      humans, and the ability to assess complex behavioral impairments that are
      difficult to test in rodents. Furthermore, results obtained from monkey studies
      translate better to applications in humans. In this review, we highlight the
      importance of alpha-synuclein in Parkinson's disease and discuss the development
      of alpha-synuclein based nonhuman primate models.

PMID- 28434077
TI  - Muscle size and strength: another study not designed to answer the question.

PMID- 28434078
TI  - Muscle size and strength: debunking the "completely separate phenomena"
      suggestion.

PMID- 28434080
TI  - Predictive risk factors for peritoneal recurrence after pancreatic cancer
      resection and strategies for its prevention.
AB  - PURPOSE: To evaluate the risk factors for peritoneal recurrence (PR) of
      pancreatic adenocarcinoma and to discuss the appropriate management strategies.
      METHODS: We reviewed the medical records of 236 patients who underwent
      pancreatectomy for pancreatic adenocarcinoma. We then compared the
      clinicopathological characteristics of patients with vs. those without PR. The
      independent risk factors for PR were defined using the Cox proportional hazards
      regression model. RESULTS: The median survival of patients with PR was 13.3
      months after surgical treatment. The PR group had a significantly higher
      incidence of portal vein resection, longer operative time (>=648 min), greater
      blood loss (>=2179 mL), blood transfusion, tumor size, portal vein invasion,
      artery invasion, pancreatic nerve plexus invasion, and histological grade.
      Multivariate analysis revealed that excessive blood loss (>=2179 mL; P = 0.010),
      artery invasion (P = 0.025), pancreatic nerve plexus invasion (P = 0.001), and
      histological grade 3 (P = 0.011) were independent risk factors for PR. Excessive
      blood loss was also strongly related to tumor size (P = 0.018). CONCLUSIONS:
      Local invasion and tumor size-related factors suggested the possibility of
      intraoperative dissemination at the time of tumor resection. Preoperative
      treatment and an operative procedure to prevent tumor exposure may help prevent
      PR.

PMID- 28434081
TI  - The outcomes of pediatric liver retransplantation from a living donor: a 17-year
      single-center experience.
AB  - PURPOSE: Liver retransplantation is the only therapeutic option for patients with
      graft failure after liver transplantation. The aim of this study is to evaluate
      the outcomes of pediatric retransplantation from living donor at a single center.
      METHODS: Between December 1998 to August 2015, retransplantation from a living
      donor was performed for 14 children (<18 years of age) at Kumamoto University
      Hospital. The characteristics of the retransplantation recipient and the
      clinicopathological factors between primary transplantation and retransplantation
      were analyzed to detect the prognostic factors. RESULTS: In retransplantation,
      the operative time was longer and the amount of blood loss was greater in
      comparison to primary transplantation. The 1-, 3-, and 5-year survival rates from
      the date of retransplantation were 85.7, 85.7, and 78.6%, respectively. The rates
      of re-laparotomy after primary transplantation, bile leakage and postoperative
      bleeding after retransplantation were higher than after primary transplantation.
      Among the three patients who died after retransplantation, the operative time,
      the rate of re-laparotomy after primary transplantation and the incidence of
      gastrointestinal complications were higher in comparison to the surviving
      patients. CONCLUSION: Pediatric retransplantation from a living donor is an
      acceptable procedure that could save the lives of recipients with failing
      allografts when organs from deceased donors are scarce. To ensure good results,
      it is essential to make an appropriate assessment of the cardiopulmonary function
      and the infectious state of the patients before Re-LDLT.

PMID- 28434079
TI  - Cell culture: complications due to mechanical release of ATP and activation of
      purinoceptors.
AB  - There is abundant evidence that ATP (adenosine 5'-triphosphate) is released from
      a variety of cultured cells in response to mechanical stimulation. The release
      mechanism involved appears to be a combination of vesicular exocytosis and
      connexin and pannexin hemichannels. Purinergic receptors on cultured cells
      mediate both short-term purinergic signalling of secretion and long-term
      (trophic) signalling such as proliferation, migration, differentiation and
      apoptosis. We aim in this review to bring to the attention of non-purinergic
      researchers using tissue culture that the release of ATP in response to
      mechanical stress evoked by the unavoidable movement of the cells acting on
      functional purinergic receptors on the culture cells is likely to complicate the
      interpretation of their data.

PMID- 28434082
TI  - Senior general surgery residents can be trained to perform focused assessment
      with sonography for trauma patients accurately.
AB  - PURPOSES: Researchers studying trauma have found that physicians are able to
      perform a focused assessment with sonography for trauma (FAST) with minimal
      training and achieve ideal accuracy. However, there are currently no consensus or
      standard guidelines regarding the performance of this assessment. The aim of our
      study was to clarify the value of FAST performed by well-qualified senior general
      surgery residents in cases of suspected blunt abdominal trauma, which presents an
      important diagnostic problem in emergency departments. METHODS: This was a
      retrospective study in the emergency department (ED) of our hospital performed
      from January 2011 to September 2013. Patients were included if they (1) had
      undergone a FAST examination performed by qualified residents and (2) had
      received subsequent formal radiographic or surgical evaluations. The results were
      compared against subsequent surgical findings or formal Department of Radiology
      reference standards. RESULTS: Among the 438 patients enrolled, false-negative
      results were obtained in 8 and false-positive results in 5. Only one patient was
      missed and required laparotomy to repair a small intestine perforation. The
      sensitivity and specificity were 87 and 99%, respectively; the accuracy was 97%.
      CONCLUSIONS: Senior general surgery residents can be trained to perform accurate
      FAST examinations on trauma patients.

PMID- 28434083
TI  - Predictors of a successful outcome for infants with short bowel syndrome: a 30
      year single-institution experience.
AB  - PURPOSE: Short-bowel syndrome (SBS) is associated with high morbidity and
      mortality. We conducted this study to establish the predictors of survival and
      weaning off parenteral nutrition (PN). METHODS: We reviewed the medical records
      of 16 SBS infants treated at our institution within a 30-year period. SBS was
      defined as a residual small-bowel length (RSBL) of <75 cm. Loss of the ileocecal
      valve (ICV), cholestasis (D-Bil >2.0 mg/dl), enterostomy, and RSBL were all
      evaluated. Kaplan-Meier analysis was used to analyze the predictors. RESULTS: The
      mean RSBL was 34.9 +/- 22.9 cm. Six patients died (37.5%) and nine patients were
      weaned off PN (56.3%). Significant differences were observed in cholestasis (p <
      0.03), enterostomy (p < 0.01), an absolute RSBL of <30 cm (p < 0.04), and a
      percentage of expected RSBL of <10% (p < 0.04) as survival predictors.
      Significant differences were also observed for cholestasis (p < 0.01), loss of
      the ICV (p < 0.04), an absolute RSBL of <20 cm (p < 0.01), and a percentage of
      expected RSBL of <10% (p < 0.03) as predictors of weaning off PN. CONCLUSION:
      These predictors may help us select the optimal treatments for pediatric patients
      with SBS.

PMID- 28434084
TI  - Population data of 23 autosomal STR loci in the Chinese Han population from
      Guangdong Province in southern China.
AB  - The genetic polymorphisms of 23 autosomal short tandem repeat (STR) loci included
      in the HuaxiaTM Platinum kit were evaluated in 1533 unrelated healthy Guangdong
      Han individuals living in the Guangdong Province in southern China. All of the
      loci reached the Hardy-Weinberg equilibrium. These loci were examined to
      determine the allele frequencies and forensic statistical parameters. The genetic
      relationship between the Guangdong Han and other Chinese populations was also
      estimated. The combined discrimination power and the probability of excluding the
      paternity of 23 STR loci were 0.999 999 999 999 999 999 999 999 999 74 and 0.999
      999 999 72, respectively. These results suggested that the 23 STR loci are highly
      polymorphic and suitable for personal forensic identification and paternity
      testing.

PMID- 28434085
TI  - Exploring the oral microflora of preschool children.
AB  - The oral cavity is one of the most important and complicated habitats in our body
      and supports diverse microbial communities. In this study, we aimed to determine
      the bacterial diversity and composition of various oral micro-niches. Samples
      were collected from supragingival plaque, saliva, and tongue coating from 10
      preschool children (30 samples total). 16S rRNA gene pyrosequencing dataset
      generated 314,639 clean reads with an average of 10,488 +/- 2,787 reads per
      sample. The phyla Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and
      Fusobacteria were predominant, accounting for more than 90% of the total
      sequences. We found the highest alpha diversity, microbial richness, and evenness
      in plaque, compared with saliva and tongue coating. Plaque was also distinguished
      from saliva and tongue coating by phylogenetic distances (weighted UniFrac). Taxa
      with different relative abundances were further identified, confirming the
      existence of microbial differences across the three niches. Core microbiomes were
      defined of each niche; however, only a small proportion of operational taxonomic
      units (8.07%) were shared by the three niches. Coaggregation between Actinomyces
      spp. and Streptococcus spp. and other correlations among periodontal pathogens,
      such as Prevotella, Fusobacteria, Capnocytophaga, and Tannerella, were shown by a
      co-occurrence network. In summary, our study provides a framework of oral
      microbial communities in the population of preschool children as a baseline for
      further studies of oral diseases related to microbes.

PMID- 28434086
TI  - The inability of Bacillus licheniformis perR mutant to grow is mainly due to the
      lack of PerR-mediated fur repression.
AB  - PerR, a member of Fur family protein, is a metal-dependent H2O2 sensing
      transcription factor that regulates genes involved in peroxide stress response.
      Industrially important bacterium Bacillus licheniformis contains three PerR-like
      proteins (PerRBL, PerR2, and PerR3) compared to its close relative Bacillus
      subtilis. Interestingly, unlike other bacteria including B. subtilis, no
      authentic perR BL null mutant could be established for B. licheniformis. Thus, we
      constructed a conditional perR BL mutant using a xylose-inducible promoter, and
      investigated the genes under the control of PerRBL. PerRBL regulon genes include
      katA, mrgA, ahpC, pfeT, hemA, fur, and perR as observed for PerRBS. However,
      there is some variation in the expression levels of fur and hemA genes between B.
      subtilis and B. licheniformis in the derepressed state. Furthermore, katA, mrgA,
      and ahpC are strongly induced, whereas the others are only weakly or not induced
      by H2O2 treatment. In contrast to the B. subtilis perR null mutant which
      frequently gives rise to large colony phenotype mainly due to the loss of katA,
      the suppressors of B. licheniformis perR mutant, which can form colonies on LB
      agar, were all catalase-positive. Instead, many of the suppressors showed
      increased levels of siderophore production, suggesting that the suppressor
      mutation is linked to the fur gene. Consistent with this, perR fur double mutant
      could grow on LB agar without Fe supplementation, whereas perR katA double mutant
      could only grow on LB agar with Fe supplementation. Taken together, our data
      suggest that in B. licheniformis, despite the similarity in PerRBL and PerRBS
      regulon genes, perR is an essential gene required for growth and that the
      inability of perR null mutant to grow is mainly due to elevated expression of
      Fur.

PMID- 28434087
TI  - Hepatitis B During Pregnancy in Endemic Areas: Screening, Treatment, and
      Prevention of Mother-to-Child Transmission.
AB  - The proper management of pregnant women infected with hepatitis B virus (HBV) is
      necessary to prevent maternal and fetal morbidity and mortality and to protect
      the baby from HBV infection. In the majority of cases, vertical transmission can
      be prevented with a universal screening program, HBV vaccine immunoprophylaxis,
      and administration of hepatitis B immunoglobulin (HBIg) for babies born to
      mothers with HBV. However, in mothers with a high viral load (>200,000 or
      >1,000,000 IU/ml, depending on the guideline), the chance of immunoprophylaxis
      failure remains high. The standard recommendation is to give an antiviral agent
      during the third trimester in these patients. US FDA pregnancy category B agents
      such as tenofovir and telbivudine are allowed through all trimesters of
      pregnancy. Breastfeeding for patients who receive antiviral agents can be allowed
      after a risk-benefit discussion with the patient.

PMID- 28434088
TI  - Addressing the Heterogeneity of Heart Failure in Future Randomized Trials.
AB  - PURPOSE OF THE REVIEW: The aim of review is to describe the essential role of
      study designs beyond RCTs in contemporary contest of HF patients giving
      perspectives on its evolving. The article concludes with concern about the
      support of observational studies for future randomized clinical trials. RECENT
      FINDINGS: With the aging population and spectacular advance in cardiovascular
      therapy, the clinical syndrome comprising heart failure (HF) is increasingly in
      complexity of heterogeneity. It remains among the most challenging of clinical
      syndromes with a magnitude of proposed pathophysiological mechanisms involving
      the heart and the interplay with cardiac and non-cardiac comorbidities. In this
      epidemiological scenario, randomized clinical trials are suffering from growing
      failed treatment, so that a deeper understanding of heterogeneity represents a
      major unmet need. This field also is greatly in a more nuanced comprehension
      about the applicability in clinical practice of trials' results derived from well
      selected HF population. Thus, we need to reflect on trials failures and the
      translation of previous trials in clinical practice in order to redirect the
      future trial intervention.

PMID- 28434089
TI  - Pregnancy and kidney disease: from medicine based on exceptions to exceptional
      medicine.
AB  - The Webster dictionary defines exception as an anomaly, a person or thing that
      does not follow a rule, while the adjective exceptional has a different nuance,
      and means "above average". These two words may describe how obstetric nephrology
      has shifted from the description of very rare cases, to the development of a
      complex new and fascinating branch of medicine, that counterbalances
      obstetricians' usually optimistic outlook by focusing on subtle challenges posed
      by chronic diseases, and mitigate the frequently grim approach of nephrologists,
      with a message of hope: women with kidney disease can have the same basic life
      goals as healthy women their age. Although studies relating to kidney disease in
      pregnancy are being published more frequently, not all questions have been
      considered or answered, and clinicians are often challenged by a lack of detailed
      information and practical guidelines. Thus in this complex, difficult, but also
      fascinating and evolving panorama, the Journal of Nephrology is publishing a
      issue dedicated to obstetric nephrology, in an attempt to contribute to the
      development of this field, with the specific aim of offering practical insights
      and critical contributions capable of helping clinicians in the management of
      these "exceptional exceptions".

PMID- 28434091
TI  - Continued Bullying Victimization in Adolescents: Maladaptive Schemas as a
      Mediational Mechanism.
AB  - Bullying victimization in adolescence is a significant social problem that can
      become persistent over time for some victims. However, there is an overall
      paucity of research examining the factors that contribute to continued bullying
      victimization. Schema therapy proposes a model that can help us understand why
      bullying victimization can be persistent for some victims. This study examines
      the role of maladaptive schemas, the key concept in schema therapy, as a
      mechanism of continued bullying victimization. The hypothesis was that
      maladaptive schemas of rejection mediate the predictive association between
      victimization in both the family and at school and future bullying victimization.
      Social anxiety was also considered, as previous research suggests that it can
      increase the risk of victimization. The participants were 1328 adolescents (45%
      female) with a mean age of 15.05 years (SD = 1.37), who completed questionnaires
      at three time points with a 6-month interval between them. Time 2 maladaptive
      schemas of rejection significantly mediated the predictive association from Time
      1 bullying victimization, family abuse and social anxiety to Time 3 bullying
      victimization. The findings pertaining to potentially malleable factors, such as
      maladaptive schemas that maintain continued interpersonal victimization, have
      important implications for prevention and treatment strategies with adolescents.

PMID- 28434090
TI  - A best practice position statement on the role of the nephrologist in the
      prevention and follow-up of preeclampsia: the Italian study group on kidney and
      pregnancy.
AB  - Preeclampsia (PE) is a protean syndrome causing a transitory kidney disease,
      characterised by hypertension and proteinuria, ultimately reversible after
      delivery. Its prevalence is variously estimated, from 3 to 5% to 10% if all the
      related disorders, including also pregnancy-induced hypertension (PIH) and HELLP
      syndrome (haemolysis, increase in liver enzyme, low platelets) are included. Both
      nephrologists and obstetricians are involved in the management of the disease,
      according to different protocols, and the clinical management, as well as the
      role for each specialty, differs worldwide. The increased awareness of the role
      of chronic kidney disease in pregnancy, complicating up to 3% of pregnancies, and
      the knowledge that PE is associated with an increased risk for development of CKD
      later in life have recently increased the interest and redesigned the role of the
      nephrologists in this context. However, while the heterogeneous definitions of
      PE, its recent reclassification, an emerging role for biochemical biomarkers, the
      growing body of epidemiological data and the new potential therapeutic
      interventions lead to counsel long-term follow-up, the lack of resources for
      chronic patients and the increasing costs of care limit the potential for
      preventive actions, and suggest tailoring specific interventional strategies. The
      aim of the present position statement of the Kidney and Pregnancy Study Group of
      the Italian Society of Nephrology is to review the literature and to try to
      identify theoretical and pragmatic bases for an agreed management of PE in the
      nephrological setting, with particular attention to the prevention of the
      syndrome (recurrent PE, presence of baseline CKD) and to the organization of the
      postpartum follow-up.

PMID- 28434092
TI  - Cyberbullying Victimization and Adolescent Mental Health: Evidence of
      Differential Effects by Sex and Mental Health Problem Type.
AB  - The use of electronic communication technologies has become a core method for
      adolescent communication. While there are many benefits to such technologies,
      cyberbullying has emerged as a potential harm. This study examines the
      association between cyberbullying and adolescent mental health problems and the
      extent to which this association differs by sex and mental health problem type. A
      clustered sample of 31,148 students in grades 6-12 (Female = 51.9%; 56.5%
      Caucasian, 10.2% South Asian) completed an anonymous survey asking their
      frequency of exposure to traditional forms of bullying, cyberbullying, and
      experiences of mental health problems over the past 6 months. Multilevel
      structural equation modelling was used to examine the associations. Controlling
      for age and traditional forms of bullying, cyberbullying was a significant
      predictor of adolescents' emotional and behavioral problems. Cyberbullying was
      more strongly associated with emotional problems for females and with behavioral
      problems for males. This evidence identifies unique adverse effects associated
      with cyberbullying on both emotional and behavioural problems and sex differences
      in the strength of these associations.

PMID- 28434093
TI  - Software to obtain accurate Gaussian expansions for a wide range of radial
      functions.

PMID- 28434095
TI  - Patient-reported outcomes in cancer survivors: a population-wide cross-sectional
      study.
AB  - PURPOSE: There is a lack of robust population-based data regarding the lived
      experience of cancer survivors. This study assessed the quality of life (QoL) of
      survivors of breast, colorectal, or prostate cancer, non-Hodgkin lymphoma or
      melanoma 1, 3 and 5 years post-diagnosis. Associations between various
      demographic and disease-related factors and QoL were assessed. METHODS: A cross
      sectional postal survey was undertaken. Eligible participants were identified
      from a population-based cancer registry. Patient-reported outcomes including QoL,
      symptom issues and information needs were collected using validated
      questionnaires. RESULTS: Difficulties with all QoL domains were more prevalent
      amongst cancer survivors compared with the general population, particularly
      difficulties with usual activities (28 vs 15%) and anxiety or depression (35 vs
      22%). Symptoms such as trouble sleeping, always feeling tired, trouble
      concentrating and fear of cancer recurrence persisted up to 5 years post
      diagnosis. Factors associated with reduced QoL included having another long
      standing health condition, cancer not responding fully to treatment, not having
      or not being certain of having a written care plan and being female. CONCLUSIONS:
      Cancer survivors experience inferior QoL and cancer-related symptoms for years
      following diagnosis. These results support further investigation into factors
      that contribute to poorer survivor outcomes and enhanced identification and
      intervention strategies for those requiring additional support.

PMID- 28434094
TI  - A systematic review of psychosocial interventions for colorectal cancer patients.
AB  - PURPOSE: A significant minority of colorectal cancer (CRC) patients experience
      clinically meaningful distress that may warrant intervention. The goal of this
      systematic review was to assess the impact of psychosocial interventions on
      quality-of-life and psychosocial outcomes for CRC patients. METHODS: A systematic
      search of CINAHL, MEDLINE, PsycINFO, and PsycARTICLES was undertaken to obtain
      relevant randomized controlled trials (RCTs) published through October 2016.
      RESULTS: Fourteen RCTs of psychosocial interventions for CRC patients were
      identified. Only three of these RCTs showed significant intervention effects on
      multiple mental health outcomes. These interventions included written and verbal
      emotional expression, progressive muscle relaxation training, and a self-efficacy
      enhancing intervention. Eight of the 14 trials, testing a range of
      psychoeducational and supportive care interventions, produced little to no
      effects on study outcomes. An evaluation of RCT quality highlighted the need for
      greater rigor in study methods and reporting. CONCLUSION: A limited evidence base
      supports the efficacy of psychosocial interventions for CRC patients. Large-scale
      trials are needed before drawing definitive conclusions regarding intervention
      impact.

PMID- 28434096
TI  - Benefits and risks of a percutaneous endoscopic gastrostomy (PEG) for
      decompression in patients with malignant gastrointestinal obstruction.
AB  - PURPOSE: Gastrointestinal obstruction presents many burdens for patients with end
      stage abdominal cancer, such as nausea and vomiting. Few detailed data on the
      efficacy of a percutaneous endoscopic gastrostomy (PEG) for decompression exists.
      This retrospective cohort study investigates the quantity of symptom relief
      realized with PEG and the corresponding complications. METHODS: Chart reviews of
      75 patients with malignant gastrointestinal obstruction, who received a PEG for
      decompression, were performed. Abstracted data includes symptoms (vomiting,
      nausea, abdominal pain) and medication up to 7 days before and after the
      intervention, complications, demographics, potential influencing factors and
      survival. Generalized estimating equations (GEE) models determined symptom
      reduction. RESULTS: PEG decreased the mean frequency of vomiting per day from 2.2
      (95% confidence interval (CI) 1.7-2.7) to 0.4 (95% CI 0.3-0.6) (p < 0.001). The
      probability of the occurrence of nausea on a given day was 80% (95% CI 74-85%)
      prior to the PEG placement and 40% (95% CI 34-47%) afterwards (p < 0.001). One
      hundred twelve complications were reported in 56 patients (none 19/75 patients
      (25%), minor 52/75 (69%), major 18/75 (24%)). Stomal leakage (18/75 patients),
      mild wound pain (17/75) and tube occlusion (13/75) occurred most frequently. The
      failure of the first attempt of the PEG placement (7/75) presented as the leading
      major complication. CONCLUSIONS: The PEG for decompression significantly reduces
      vomiting and nausea in patients with malignant gastrointestinal obstruction (p <
      0.001). Minor complications are common and should be discussed prior to the
      intervention. Nevertheless, the PEG appears to demonstrate prevailing benefits in
      comparison to the risks.

PMID- 28434097
TI  - Impact of a complementary/integrative medicine program on the need for supportive
      cancer care-related medications.
AB  - OBJECTIVE: Despite the growing evidence supporting the use of
      complementary/integrative medicine (CIM) in the treatment of chemotherapy-induced
      toxicities, little is known on CIM impact of these therapies regarding the use of
      medications for supportive cancer care. In this study, we examined the impact of
      CIM on the need for supportive cancer care-related medications. PATIENTS AND
      METHODS: Patients with breast or gynecological cancer referred to and attending
      an integrative physician (IP) consultation for gastrointestinal (GI) concerns
      were designated as the treatment group; those not attending as controls.
      Adherence to the integrative care program (AIC) was defined as attending >=4 CIM
      interventions. The need for conventional supportive care-related medications and
      doses was determined from patients' medical files, as well as the implications on
      the potential for cost reduction. RESULTS: Of the 205 patients diagnosed with GI
      concerns, 116 attended the IP consultation and weekly CIM treatments (56.6%;
      treatment group), of which 85 (73.3%) were adherent to the program (AIC
      subgroup); 89 did not undergo an IP consultation (43.4%; controls). Within-group
      analysis found a greater decrease in the use of non-opioid analgesics (NOAs) at 6
      weeks in the treatment group (P = 0.01), more so in the AIC subgroup (P = 0.02).
      A cost analysis suggests that reduced NOA use in the treatment group reduced the
      cost of supportive care, covering 27.1% of the overall expense of CIM treatments.
      Controls were less likely to require anti-emetics (P = 0.007). Between-group
      analysis showed a trend for reduced use of anxiolytics (P = 0.06) and NOAs (P =
      0.08) among treated patients, with lower dose equivalents for NOAs than controls
      (P < 0.001). CONCLUSION: CIM treatments may reduce the need for NOAs among
      patients with breast or gynecological cancer.

PMID- 28434098
TI  - Changes to taxonomy and the International Code of Virus Classification and
      Nomenclature ratified by the International Committee on Taxonomy of Viruses
      (2017).
AB  - This article lists the changes to virus taxonomy approved and ratified by the
      International Committee on Taxonomy of Viruses (ICTV) in March 2017.

PMID- 28434099
TI  - The complete genome sequence of a novel virus, bellflower veinal mottle virus,
      suggests the existence of a new genus within the family Potyviridae.
AB  - A new virus was isolated from a bellflower (Campanula takesimana) plant showing
      veinal mottle symptoms, and its complete genome sequence was determined. The
      viral genome consists of a positive-sense single-stranded RNA of 8,259
      ribonucleotides. Electron microscopic observation revealed that the viral genome
      is packaged as a filamentous particle with an average length of approximately 760
      nm. BLAST searches of protein databases showed that the encoded polyprotein has a
      maximum amino acid sequence identity of 34.1% (with 95% coverage) to that of the
      isolate AD of Chinese yam necrotic mosaic virus (CYNMV; genus Macluravirus).
      Phylogenetic analysis and comparison of the encoded amino acid sequences with
      those of other viruses demonstrated that the identified virus shows minimal
      sequence similarity to known viruses and should therefore be considered a member
      of a new genus in the family Potyviridae. The name bellflower veinal mottle virus
      (BVMoV) is proposed for this new virus.

PMID- 28434100
TI  - Complete genome sequence of jacquemontia yellow vein virus, a novel begomovirus
      infecting Jacquemontia tamnifolia in Venezuela.
AB  - Wild plants of the family Convolvulaceae are hosts for a few New World
      begomoviruses (genus Begomovirus, family Geminiviridae). In this work, we report
      the complete genome sequence of a new begomovirus infecting the wild
      convolvulaceous plant Jacquemontia tamnifolia in Venezuela. The cloned bipartite
      genome showed the organization of typical New World begomoviruses and was found
      to be phylogenetically related to those of begomoviruses from Venezuela and other
      Caribbean countries. Several recombination events have been shown to have
      occurred involving genome fragment exchange with related begomoviruses infecting
      crops such as tomato and cucurbits and wild plants, including Jacquemontia sp. We
      propose the name jacquemontia yellow vein virus (JacYVV) for this new
      begomovirus.

PMID- 28434101
TI  - Predicting Dream Recall: EEG Activation During NREM Sleep or Shared Mechanisms
      with Wakefulness?
AB  - The common knowledge of a uniqueness of REM sleep as a privileged scenario of
      dreaming still persists, although consolidated empirical evidence shows that the
      assumption that dreaming is just an epiphenomenon of REM sleep is no longer
      tenable. However, the brain mechanisms underlying dream generation and its
      encoding in memory during NREM sleep are still mostly unknown. In fact, only few
      studies have investigated on the mechanisms of dream phenomenology related to
      NREM sleep. For this reason, our study is specifically aimed to elucidate the
      electrophysiological (EEG) correlates of dream recall (DR) upon NREM sleep
      awakenings. Under the assumption that EEG activity predicts the presence/absence
      of DR also during NREM sleep, we have investigated whether DR from stage 2 NREM
      sleep shares similar brain mechanisms to those involved in the encoding of
      episodic memory during wakefulness, or it depends on the specific
      electrophysiological milieu of the sleep period along the
      desynchronized/synchronized EEG continuum. We collected DR from a multiple nap
      protocol in a within-subjects design. We found that DR is predicted by an
      extensive reduction of delta activity during the last segment of sleep,
      encompassing left frontal and temporo-parietal areas. The results could represent
      an update on the mechanisms underlying the sleep mentation during NREM sleep. In
      particular, they support the hypothesis that an increased cortical EEG activation
      is a prerequisite for DR, and they are not necessarily in conflict with the
      hypothesis of common wake-sleep mechanisms. We also confirmed that EEG correlates
      of DR depend on a state-like relationship.

PMID- 28434102
TI  - Outcomes Following Surgical Management of Cauda Equina Syndrome: Does Race
      Matter?
AB  - Cauda equina syndrome (CES) is a surgical emergency requiring urgent spinal
      decompression. Our objective is to analyze the association between race and in
      hospital outcomes (complications, mortality, length of stay, and discharge
      disposition) in patients with CES. This is a retrospective cohort study of CES
      patients identified via the Nationwide Inpatient Sample (NIS) from 2000 to 2010
      in inpatient hospitalizations in the USA. The patient sample includes 46,017
      patients >=18 undergoing spine surgery for CES. Using ICD9-CM codes, patient
      records with a diagnosis of CES from 2003 to 2010 were selected from the NIS
      database and sorted by mortality, complications, length of hospital stay, and
      discharge status. Demographic information (age, gender, race, and insurance
      status) and hospital characteristics were evaluated. African-American patients
      were 1.38-fold (p < 0.02; 95% odds ratio [OR] 1.05-1.83) more likely than
      Caucasian patients to develop complications based on a multivariate logistic
      regression model adjusted for patient age, insurance status, surgical approach,
      and hospital size. There was no difference in mortality among patients of various
      races in both univariate and multivariate analysis. A multivariate linear
      regression model adjusted for insurance status, surgical approach, and hospital
      size revealed that, compared to Caucasian patients, length of hospitalization in
      African-American patients was 1.92 days longer (p < 0.01), 1.34 days longer (p <
      0.01) in Hispanic patients, and 2.24 days longer (p < 0.01) in Asian-American
      patients. African-American patients were 0.59-fold (p < 0.01; 95% OR 0.494-0.708)
      less likely than Caucasian patients to have routine discharge to home. African
      American patients hospitalized for surgical management of CES experience
      significantly more complications, longer length of hospitalizations, and higher
      discharge to non-home locations, compared to Caucasian patients.

PMID- 28434103
TI  - Structure restraints from heteronuclear pseudocontact shifts generated by
      lanthanide tags at two different sites.
AB  - Pseudocontact shifts (PCS) encode long-range information on 3D structures of
      protein backbones and side-chains. The level of structural detail that can be
      obtained increases with the number of different sites tagged with a paramagnetic
      metal ion to generate PCSs. Here we show that PCSs from two different sites can
      suffice to determine the structure of polypeptide chains and their location and
      orientation relative to the magnetic susceptibility tensor chi, provided that
      PCSs are available for 1H as well as heteronuclear spins. In addition, PCSs from
      two different sites are shown to provide detailed structural information on the
      conformation of methyl group-bearing amino-acid side-chains. A previously
      published ensemble structure of ubiquitin is shown to explain the magnetic
      susceptibility and alignment tensors slightly better than structures that try to
      explain the experimental data by a single conformation, illustrating the
      potential of PCSs as a tool to investigate small conformational changes.

PMID- 28434104
TI  - Mullerian dysgenesis: a critical review of the literature.
AB  - PURPOSE: To present an update of the genetic, clinical, diagnostic, and
      therapeutic aspects of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. METHODS:
      Studies were considered eligible if they have evaluated patients with MRKH
      syndrome. Eligible articles were identified by a search of MEDLINE
      bibliographical database from 1950 to August 2016. A purely descriptive approach
      was adopted concerning all outcomes examined by the individual studies. RESULTS:
      MRKH syndrome is defined as congenital aplasia of the upper vagina and impairment
      of uterine development in normal 46XX females. Accounting for 1:4500 women, MRKH
      is the second most common cause of primary amenorrhea following gonadal
      dysgenesis. Potential association of MRKH syndrome to specific genes has been the
      focus of recent research. Null-association results of HOXA genes and Wnt5a,
      Wnt7a, and Wnt9a have been reported, while point mutations of the WNT4 gene point
      mutations have been associated with an MRKH-like syndrome characterized by
      Mullerian duct regression and hyperandrogenism. Ultrasound and Magnetic Resonance
      Imaging (MRI) are the main techniques to establish an accurate diagnosis of the
      syndrome. Several non-surgical and surgical procedures have been reported for the
      creation of a functional neovagina; in general, non-surgical treatment should be
      the first initially pursued. Along with psychological support, recent
      developments in assisted reproductive technologies of IVF techniques and the
      availability of gestational surrogacy, as well as the recent breakthrough of
      successful uterus transplantation, enable women with MRKH syndrome to attain
      their own genetic child. CONCLUSION(S): MRKH syndrome is a medical modality with
      important social, legal, and ethical projections that require a multi
      disciplinary approach.

PMID- 28434105
TI  - Far-infrared ray for treating chronic lower extremity lymphedema with
      dermatolymphangioadenitis: a postoperative complication of gynecological tumor
      resection.
AB  - PURPOSE: Lower extremity lymphedema is regarded as a relatively common
      postoperative complication and is often accompanied with
      dermatolymphangioadenitis (DLA). This study combines clinical assessment and
      laboratory investigation to explore therapeutic effects of far-infrared radiation
      (FIR) therapy for chronic lower extremity lymphedema accompanied with DLA,
      occurring after gynecological tumor resection. METHODS: Patients who met
      inclusion and exclusion criteria would be enrolled. They received regular
      sessions using the FIR therapy machine over the 4-week treatment course. Clinical
      and laboratory outcome measures were carried out before and after treatment.
      Clinical outcome measures included DLA seizure frequency (episodes/year),
      patients' subjective feedback for lymphedema-related symptoms and quality of life
      (QOL). Laboratory outcome measures included bacterial cultures and concentrations
      of inflammatory cytokines: IL-1beta, IL-2, IL-4, IL-10, IL-12, IL-18, TNF-alpha,
      TNF-beta, caspase-1 and INF-gamma, detected in serum and local lymphedema tissue
      fluid samples using protein microarray and ELISA. RESULTS: Between 2012 and 2016,
      a total of 120 female patients were screened for study enrollment. Sixty-four
      recruited patients underwent clinical evaluation both before FIR radiation
      therapy and 1 year after a single course of FIR radiation therapy. Eleven
      patients (17.2%), randomly chosen from the study group, underwent additional
      laboratory analysis of blood and local lymphedema tissue fluid samples. The
      frequency of DLA decreased following treatment (p < 0.001). Fifty patients (78%)
      did not experience a single episode of DLA recurrence in the year subsequent to
      treatment. The efficiency rate calculated using DLA frequencies was greater than
      50% for 63 (98%) patients following treatment. Patients reported a subjective
      decrease in lymphedema-related symptoms (p < 0.05). Patients' QOL scores were
      higher after treatment (p < 0.001). Laboratory analysis showed an elevation in
      serum concentration of IL-1beta after FIR therapy (p < 0.05) and reduced local
      tissue fluid concentrations of inflammatory cytokines IL-2, IL-10 and IL-18 (p <
      0.05). Bacterial culture results before and after treatment were both negative.
      CONCLUSION: FIR radiation therapy provides an effective treatment modality for
      patients with chronic lymphedema accompanied with DLA that develops secondarily
      to treatment of gynecological malignancies, whose therapeutic effects may be due
      to reduced immune dysfunction within local lymphedema tissues.

PMID- 28434106
TI  - What do patients want to know about contraception and which method would they
      prefer?
AB  - PURPOSE: The aim of this study was to determine the extent to which women's
      choice of contraceptive method depends on the advice received from their
      gynecologist and whether more intensive counseling might lead to more frequent
      use of long-acting reversible contraception (LARC). METHODS: A total of 1089
      physicians and 18,521 women responded to 32 or 37 questions, respectively, using
      an online questionnaire. The women were asked about their current use of
      contraceptive methods, the extent of their satisfaction with them, their
      satisfaction with the counseling they had received, and whether they wanted to
      have more information about contraception. The physicians were similarly asked
      which contraceptive methods were being used, how satisfied with them they were,
      how they would assess their patients' satisfaction with them, and whether the
      women wanted to have more information. RESULT: The results showed that 61% of the
      women were using oral contraceptives, and a total of only 9% were using behavior
      independent long-term contraceptive methods. However, 60% of the women stated
      that long-term contraception would be an option for them if they had more
      information about it. Gynecologists underestimated this figure, at only 18%.
      Whereas 66% of the gynecologists believed that their patients never forgot to
      take the pill, nearly, half of the women stated that they had forgotten it at
      least once during the previous 3 months. CONCLUSION: The small number of women
      who use long-term contraception is in clear contrast to the fact that many women
      want to have a very safe but also behavior-independent method.

PMID- 28434107
TI  - Early-Life Obesity Prevention: Critique of Intervention Trials During the First
      One Thousand Days.
AB  - PURPOSE OF REVIEW: To critique the evidence from recent and ongoing obesity
      prevention interventions in the first 1000 days in order to identify evidence
      gaps and weaknesses, and to make suggestions for more informative future
      intervention trials. RECENT FINDINGS: Completed and ongoing intervention trials
      have had fairly modest effects, have been limited largely to high-income
      countries, and have used relatively short-term interventions and outcomes.
      Comparison of the evidence from completed prevention trials with the evidence
      from systematic reviews of behavioral risk factors shows that some life-course
      stages have been neglected (pre-conception and toddlerhood), and that
      interventions have neglected to target some important behavioral risk factors
      (maternal smoking during pregnancy, infant and child sleep). Finally, while
      obesity prevention interventions aim to modify body composition, few intervention
      trials have used body composition measures as outcomes, and this has limited
      their sensitivity to detect intervention effects. The new WHO Healthy Lifestyles
      Trajectory (HeLTI) initiative should address some of these weaknesses. Future
      early obesity prevention trials should be much more ambitious. They should,
      ideally: extend their interventions over the first 1000 days; have longer-term
      (childhood) outcomes, and improved outcome measures (body composition measures in
      addition to proxies for body composition such as the BMI for age); have greater
      emphasis on maternal smoking and child sleep; be global.

PMID- 28434108
TI  - Emotional Eating, Binge Eating and Animal Models of Binge-Type Eating Disorders.
AB  - PURPOSE OF REVIEW: The objective of this paper is to review the role that hedonic
      factors, emotions and self-regulation systems have over eating behaviours from
      animal models to humans. RECENT FINDINGS: Evidence has been found to suggest that
      for some high-risk individuals, obesity/binge eating may develop as an impulsive
      reaction to negative emotions that over time becomes a compulsive habit. Animal
      models highlight the neural mechanisms that might underlie this process and
      suggest similarities with substance use disorders. Emotional difficulties and
      neurobiological factors have a role in the aetiology of eating and weight
      disorders. Precise treatments targeted at these mechanisms may be of help for
      people who have difficulties with compulsive overeating.

PMID- 28434110
TI  - The risk of radiation necrosis following stereotactic radiosurgery with
      concurrent systemic therapies.
AB  - To investigate late toxicity among patients with newly-diagnosed brain metastases
      undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies
      with or without whole-brain radiation therapy (WBRT). Patients with newly
      diagnosed brain metastasis who underwent SRS at a single tertiary-care
      institution from 1997 to 2015 were eligible for inclusion. The class and timing
      of all systemic therapies were collected for each patient. The primary outcome
      was the cumulative incidence of radiographic radiation necrosis (RN).
      Multivariable competing risks regression was used to adjust for confounding.
      During the study period, 1650 patients presented with 2843 intracranial
      metastases. Among these, 445 patients (27%) were treated with SRS and concurrent
      systemic therapy. Radiographic RN developed following treatment of 222 (8%)
      lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences
      of RN among lesions treated with and without concurrent therapies were 6.6 and
      5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a
      significantly increased rate of RN among lesions treated with upfront SRS and
      WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies
      significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p
      < 0.01). Among these therapies, significantly increased rates of RN were observed
      with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR
      TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely
      delivered concurrently with SRS in the management of newly-diagnosed brain
      metastases. However, the rate of radiographic RN is significantly increased with
      the addition of concurrent systemic therapies to SRS and WBRT.

PMID- 28434109
TI  - Insights into the Link Between Obesity and Cancer.
AB  - PURPOSE OF REVIEW: Adipocytes have adapted to store energy in the form of lipid
      and also secrete circulating factors called adipokines that signal to other
      tissues to coordinate energy homeostasis. These functions are disrupted in the
      setting of obesity, promoting the development of diseases such as diabetes,
      cardiovascular disease, and cancer. RECENT FINDINGS: Obesity is linked to an
      increased risk of many types of cancer and increased cancer-related mortality.
      The basis for the striking association between obesity and cancer is not well
      understood. Here, we review the cellular and molecular pathways that appear to be
      involved in obesity-driven cancer. We also describe possible therapeutic
      considerations and highlight important unanswered questions in the field.

PMID- 28434111
TI  - IDH mutation and 1p19q codeletion distinguish two radiological patterns of
      diffuse low-grade gliomas.
AB  - Diffuse low-grade gliomas (DLGG) prognosis is variable, depending on several
      factors, including the isocitrate dehydrogenase (IDH) mutation and the 1p19q
      codeletion. A few studies suggested associations between these parameters and
      tumor radiological characteristics including topography. Our aim was analyzing
      the correlations between the IDH and 1p19q statuses and the tumor intracerebral
      distribution (at the lobar and voxel levels), volume, and borders. We conducted a
      retrospective, monocentric study on a consecutive series of 198 DLGG patients.
      The IDH and 1p19q statuses were recorded. The pre-treatment magnetic resonance
      FLAIR imagings were reviewed for determination of lobar topography, tumor volume,
      and characterisation of tumor borders (sharp or indistinct). We conducted a voxel
      based lesion-symptom mapping analysis to investigate the correlations between the
      IDH and 1p19q statuses and topography at the voxel level. The IDH mutation and
      1p19q statuses were correlated with the tumor topography defined using lobar
      anatomy (p < 0.001 and p = 0.004, respectively). Frontal tumors were more
      frequently IDH-mutant (87.1 vs. 57.4%) and 1p19q codeleted (45.2 vs. 17.0%) than
      temporo-insular lesions. At the voxel level, these associations were not found.
      Tumors with sharp borders were more frequently IDH-mutant (p = 0.001) while
      tumors with indistinct borders were more frequently IDH wild-type and 1p19q non
      codeleted (p < 0.001). Larger tumors at diagnosis (possibly linked to a slower
      growth rate) were more frequently IDH-mutant (p < 0.001). IDH wild-type, 1p19q
      non-codeleted temporo-insular tumors are distinct from IDH-mutant, 1p19q
      codeleted frontal tumors. Further studies are needed to determine whether the
      therapeutic strategy should be adapted to each pattern.

PMID- 28434112
TI  - Dendritic cell based vaccination strategy: an evolving paradigm.
AB  - Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed
      primary intracranial malignancies in adults. Currently available treatments have
      provided only modest improvements in overall survival and remain limited by
      inevitable local recurrence, necessitating exploration of novel therapies. Among
      approaches being investigated, one of the leading contenders is immunotherapy,
      which aims to modulate immune pathways to stimulate the selective destruction of
      malignant cells. Dendritic cells (DCs) are potent initiators of adaptive immune
      responses and therefore crucial players in the development and success of
      immunotherapy. Clinical trials of various DC-based vaccinations have demonstrated
      the induction of anti-tumor immune responses and prolonged survival in the
      setting of many cancers. In this review, we summarize current literature
      regarding DCs and their role in the tumor microenvironment, their application and
      current clinical use in immunotherapy, current challenges limiting their efficacy
      in anti-cancer therapy, and future avenues for developing successful anti-tumor
      DC-based vaccines.

PMID- 28434114
TI  - A 4-year phase II study of everolimus in NF2 patients with growing vestibular
      schwannomas.

PMID- 28434113
TI  - Precision knockdown of EGFR gene expression using radio frequency electromagnetic
      energy.
AB  - Electromagnetic fields (EMF) in the radio frequency energy (RFE) range can affect
      cells at the molecular level. Here we report a technology that can record the
      specific RFE signal of a given molecule, in this case the siRNA of epidermal
      growth factor receptor (EGFR). We demonstrate that cells exposed to this EGFR
      siRNA RFE signal have a 30-70% reduction of EGFR mRNA expression and ~60%
      reduction in EGFR protein expression vs. control treated cells. Specificity for
      EGFR siRNA effect was confirmed via RNA microarray and antibody dot blot array.
      The EGFR siRNA RFE decreased cell viability, as measured by Calcein-AM measures,
      LDH release and Caspase 3 cleavage, and increased orthotopic xenograft survival.
      The outcomes of this study demonstrate that an RFE signal can induce a specific
      siRNA-like effect on cells. This technology opens vast possibilities of targeting
      a broader range of molecules with applications in medicine, agriculture and other
      areas.

PMID- 28434115
TI  - Interaction of Selected Phenylpropenes with Dipalmitoylphosphatidylcholine
      Membrane and Their Relevance to Antibacterial Activity.
AB  - The effect of structurally closely related phenylpropenes (PPs), estragole,
      anethole, eugenol, and isoeugenol, on the fluidity of dipalmitoyl phosphatidyl
      choline (DPPC) liposome membrane was investigated by DSC, Raman, and fluorescence
      anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH). Liposomes were prepared by
      thin-film hydration method at various DPPC:PP molar ratios. The DPH anisotropy
      measurements of blank and PP-loaded liposomes were performed at 28, 41, and 50 
      degrees C, which correspond, respectively, to gel phase, main transition
      temperature of DPPC, and liquid phase. The Raman images showed the formation of
      nano- and micrometric spherical multi-lamellar vesicles. All studied PPs
      exhibited a membrane fluidizing effect which was reinforced by the presence of
      phenolic hydroxyl group in eugenol and isoeugenol. The PPs interacted with the
      choline head group and the alkyl chains of DPPC membrane, wherein isoeugenol and
      anethole possessing the same C7-C8 position of the double bond in the propenyl
      side chain, incorporated deeply in the bilayer. Additionally, the PPs were
      analyzed for antibacterial activity against E. coli by macrobroth dilution
      method. Anethole and estragole were more efficient in inhibiting the bacterial
      growth than eugenol and isoeugenol. We conclude that the fluidizing effect of PPs
      on the membrane is a common mechanism that is not related to the hydrophobicity
      of the PP molecule. Besides, other target sites may be involved in PP
      antibacterial activity against Gram-negative bacteria. The greater hydrophobicity
      of these PPs may contribute to their penetrability through the outer bacterial
      membrane.

PMID- 28434116
TI  - Activation of the Serotonin Pathway is Associated with Poor Outcome in COPD
      Exacerbation: Results of a Long-Term Cohort Study.
AB  - BACKGROUND/INTRODUCTION: Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan
      to kynurenine. An increase of its activity is associated with severity in
      patients with pneumonia. In chronic obstructive pulmonary disease (COPD)
      patients, an elevation of serotonin has been reported. Experimental models showed
      that cigarette smoke inhibits monoamine oxidase (MAO) leading to higher levels of
      serotonin. We investigated the prognostic ability of tryptophan, serotonin,
      kynurenine, IDO, and tryptophan hydroxylase (TPH) to predict short- and long-term
      outcomes in patients with a COPD exacerbation. METHODS: We measured tryptophan,
      serotonin, and kynurenine on admission plasma samples in patients with a COPD
      exacerbation from a previous trial by liquid chromatography coupled with tandem
      mass spectrometry (LC-MS/MS). IDO and TPH were calculated as ratios of kynurenine
      over tryptophan, and serotonin over tryptophan, respectively. We studied their
      association with parameters measured in clinical routine at emergency department
      admission representing inflammation (C-reactive protein [CRP]), infection
      (procalcitonin [PCT]), oxygenation (SpO2), as well as patients' clinical outcome,
      confirmed by structured phone interviews. RESULTS: Mortality in the 149 included
      patients was 53.7% within six years of follow-up. While IDO activity showed
      strong positive correlations, tryptophan was negatively correlated with CRP and
      PCT. For 30-day adverse outcome defined as death and/or intensive care unit (ICU)
      admission, a multivariate regression analysis adjusted for age and comorbidities
      found strong associations for IDO activity (adjusted odds ratios of 31.4 (95%CI
      1.1-857), p = 0.041) and TPH (adjusted odds ratios 27.0 (95%CI 2.2-327), p =
      0.010). TPH also showed a significant association with mortality at 18 months,
      (hazard ratio 2.61 (95%CI 1.2-5.8), p = 0.020). CONCLUSION: In hospitalized
      patients with a COPD exacerbation, higher IDO and TPH activities independently
      predicted adverse short-term outcomes and TPH levels were also predictive of 18
      month mortality. Whether therapeutic modulation of the serotonin pathway has
      positive effects on outcome needs further investigation.

PMID- 28434117
TI  - Associations of TIM-1 Genetic Polymorphisms with Asthma: A Meta-analysis.
AB  - PURPOSE: Recently, the roles of TIM-1 genetic polymorphisms in asthma have been
      extensively studied, with conflicting results. Therefore, we performed the
      present meta-analysis to better assess potential associations of TIM-1 genetic
      polymorphisms with asthma. METHODS: Eligible articles were searched in PubMed,
      Medline, EMBASE, Google Scholar, and CNKI up to December 2016. Odds ratios (ORs)
      and 95% confidence intervals (CIs) were used to detect any potential associations
      between TIM-1 genetic polymorphisms and asthma. RESULTS: A total of 12 articles
      including 3120 asthma patients and 2825 control subjects were analyzed. The
      overall and subgroup analyses revealed that TIM-1-416G>C single nucleotide
      polymorphism was significantly associated with asthma for the Asian population in
      the codominant (G/G vs. G/C, p = 0.0003, OR 1.86, 95% CI 1.33-2.60) and dominant
      (G/G vs. G/C + C/C, p < 0.0001, OR 1.94, 95% CI 1.40-2.69) genetic models.
      Nevertheless, we failed to detect any significant associations between TIM-1
      416G>C single nucleotide polymorphism and asthma in Caucasians. Additionally,
      according to our analyses, TIM-1 5383_5397 insertion/deletion polymorphism was
      not correlated with asthma in both Asians and Caucasians. CONCLUSIONS: In
      conclusion, our findings suggest that TIM-1-416G>C single nucleotide polymorphism
      is associated with asthma susceptibility for the Asian ethnicity in certain
      genetic models. However, TIM-1 5383_5397 insertion/deletion polymorphism may not
      be correlated with the risk of asthma.

PMID- 28434118
TI  - Hyperoside inhibits the effects induced by oxidized low-density lipoprotein in
      vascular smooth muscle cells via oxLDL-LOX-1-ERK pathway.
AB  - Hyperoside is a major active constituent in many medicinal plants traditionally
      used in Chinese medicines for their anti-inflammatory, antioxidative, and
      vascular protective effects. Recent studies have focused on the protective
      effects of hyperoside on hyperlipidemia. However, the molecular mechanisms
      underlying these effects are unknown. In this study, vascular smooth muscle cells
      (VSMCs) were treated in vitro with oxidized low-density lipoprotein (oxLDL) in
      the presence or absence of hyperoside. Western blotting, quantitative PCR, and
      tetrazolium assay were used to detect lectin-like oxLDL receptor-1 (LOX-1)
      expression and extracellular signal-regulated kinases (ERK) activation, and to
      determine VSMCs viability. The results demonstrated that oxLDL promoted LOX-1
      expression, ERK activation, and proliferation in VSMCs. Hyperoside significantly
      inhibited the oxLDL-stimulated effects after long time exposure. However, it
      promoted ERK activation directly following a short incubation duration (25 min).
      In conclusion, hyperoside inhibits oxLDL-induced LOX-1 expression, ERK
      activation, and cell proliferation through the oxLDL-LOX-1-ERK pathway in VSMCs.
      Our findings suggest a novel role of hyperoside in treating and preventing
      atherosclerosis.

PMID- 28434119
TI  - Cost analysis for the implementation of a medication review with follow-up
      service in Spain.
AB  - Background Medication review with follow-up (MRF) is a professional pharmacy
      service proven to be cost-effective. Its broader implementation is limited,
      mainly due to the lack of evidence-based implementation programs that include
      economic and financial analysis. Objective To analyse the costs and estimate the
      price of providing and implementing MRF. Setting Community pharmacy in Spain.
      Method Elderly patients using poly-pharmacy received a community pharmacist-led
      MRF for 6 months. The cost analysis was based on the time-driven activity based
      costing model and included the provider costs, initial investment costs and
      maintenance expenses. The service price was estimated using the labour costs,
      costs associated with service provision, potential number of patients receiving
      the service and mark-up. Main outcome measures Costs and potential price of MRF.
      Results A mean time of 404.4 (SD 232.2) was spent on service provision and was
      extrapolated to annual costs. Service provider cost per patient ranged from ?196
      (SD 90.5) to ?310 (SD 164.4). The mean initial investment per pharmacy was ?4594
      and the mean annual maintenance costs ?3,068. Largest items contributing to cost
      were initial staff training, continuing education and renting of the patient
      counselling area. The potential service price ranged from ?237 to ?628 per
      patient a year. Conclusion Time spent by the service provider accounted for 75
      95% of the final cost, followed by initial investment costs and maintenance
      costs. Remuneration for professional pharmacy services provision must cover
      service costs and appropriate profit, allowing for their long-term
      sustainability.

PMID- 28434120
TI  - Involvement of Fas/FasL pathway in the murine model of atopic dermatitis.
AB  - OBJECTIVE AND DESIGN: The aim of this study was to elucidate the role of
      apoptosis mediated through Fas/FasL pathway using the mouse model of atopic
      dermatitis (AD). MATERIALS AND TREATMENT: AD was induced by epicutaneous
      application of ovalbumin (OVA) in wild-type C57BL/6, B6. MRL-Faslpr/J (Fas-) and
      B6Smn.C3-Faslgld/J (FasL-) mouse strains. METHODS: Skin samples were subjected to
      staining for Fas/FasL expression, M30 epitope and assessment of inflammatory
      response via immunohistochemical staining. Cytokine and chemokine production was
      assessed by real-time PCR. RESULTS: In comparison to wild-type mice, OVA
      sensitization of Fas- and FasL-deficient mice led to increased epidermal and
      dermal thickness, collagen deposition and local inflammation consisting of
      macrophages, neutrophils and CD4+ T cells. Fas- and FasL-deficient mice showed
      increased total counts of regulatory T cells (Tregs) and IgE levels in blood as
      well as increased expression of IL-1beta, IL-4, IL-5, IL-13 and TGF-1beta mRNA in
      comparison to wild-type mice. On the other hand, expression of CXCL9 and CXCL10,
      IL-17 mRNAs in the skin samples in Fas- and FasL-deficient mice was decreased.
      CONCLUSIONS: Our results show that lack of the Fas-induced apoptosis leads to
      exacerbation of AD characteristics such as Th2 inflammation and dermal
      thickening. Therefore, Fas receptor can play an important role in AD pathogenesis
      by controlling development of the local inflammation.

PMID- 28434121
TI  - Intracellular position of mitochondria in mesophyll cells differs between C3 and
      C4 grasses.
AB  - In C3 plants, part of the CO2 fixed during photosynthesis in chloroplasts is
      released from mitochondria during photorespiration by decarboxylation of glycine
      via glycine decarboxylase (GDC), thereby reducing photosynthetic efficiency. The
      apparent positioning of most mitochondria in the interior (vacuole side of
      chloroplasts) of mesophyll cells in C3 grasses would increase the efficiency of
      refixation of CO2 released from mitochondria by ribulose 1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) in chloroplasts. Therefore, in mesophyll cells of
      C4 grasses, which lack both GDC and Rubisco, the mitochondria ought not to be
      positioned the same way as in C3 mesophyll cells. To test this hypothesis, we
      investigated the intracellular position of mitochondria in mesophyll cells of 14
      C4 grasses of different C4 subtypes and subfamilies (Chloridoideae,
      Micrairoideae, and Panicoideae) and a C3-C4 intermediate grass, Steinchisma
      hians, under an electron microscope. In C4 mesophyll cells, most mitochondria
      were positioned adjacent to the cell wall, which clearly differs from the
      positioning in C3 mesophyll cells. In S. hians mesophyll cells, the positioning
      was similar to that in C3 cells. These results suggest that the mitochondrial
      positioning in C4 mesophyll cells reflects the absence of both GDC and Rubisco in
      the mesophyll cells and the high activity of phosphoenolpyruvate carboxylase. In
      contrast, the relationship between the mitochondrial positioning and enzyme
      distribution in S. hians is complex, but the positioning may be related to the
      capture of respiratory CO2 by Rubisco. Our study provides new possible insight
      into the physiological role of mitochondrial positioning in photosynthetic cells.

PMID- 28434122
TI  - The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5,
      STAT4, IRAK1, and CTGF polymorphisms.
AB  - Pulmonary fibrosis (PF) is one of the leading causes of death in systemic
      sclerosis (SSc) patients. Although all SSc patients are characterized by
      autoimmunity, only part of them suffer from PF, suggesting that beside
      autoimmunity, some additional factors are involved in the initiation of PF in
      SSc. In this study, we aimed to identify genetic polymorphisms associated with
      the status of PF in SSc. We performed that an exhaustive search of the PubMed
      database was performed to identify eligible studies. Then, a comprehensive meta
      analysis was performed by comparing PF+-SSc and PF--SSc patients to identify
      genetic polymorphisms associated with the status of PF in SSc. Among eight SSc
      associated susceptibility polymorphisms which were applied for meta-analysis,
      IRF5 rs2004640 polymorphism (OR 1.12; 95% CI 1.02-1.22, P = 1.39 * 10-2), STAT4
      rs7574865 polymorphism (OR 1.25; 95% CI 1.07-1.47, P = 5.3 * 10-3), IRAK1
      rs1059702 polymorphism (OR 1.20; 95% CI 1.05-1.37, P = 0.007), and CTGF G-945C
      polymorphism (OR 1.42; 95% CI 1.18-1.71, P = 0.002) are associated with PF status
      in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5
      rs10488631 polymorphisms are not. Since IRF5, STAT4, and IRAK1 are important
      regulatory factors in the control of innate immune responses and CTGF is involved
      in the synthesis of extracellular matrix, these results suggest a role of the
      innate immunity and matrix compounds in the pathogenesis of PF in SSc.

PMID- 28434123
TI  - Conversion Disorder, Functional Neurological Symptom Disorder, and Chronic Pain:
      Comorbidity, Assessment, and Treatment.
AB  - PURPOSE OF REVIEW: This paper examines the overlap of conversion disorder with
      chronic pain conditions, describes ways to assess for conversion disorder, and
      provides an overview of evidence-based treatments for conversion disorder and
      chronic pain, with a focus on conversion symptoms. RECENT FINDINGS: Conversion
      disorder is a significant problem that warrants further study, given that there
      are not many well-established guidelines. Accurate and timely assessment should
      help move treatment in a more fruitful direction and avoid unnecessary medical
      interventions. Advances in neuroimaging may also help further our understanding
      of conversion disorder. Creating a supportive environment and a collaborative
      treatment relationship and improving understanding of conversion symptoms appear
      to help individuals diagnosed with conversion disorder engage in appropriate
      treatments. Novel uses of earlier treatments, such as hypnosis and psychodynamic
      approaches, could potentially be beneficial and require a more vigorous and
      systematic study. There are treatments that produce significant improvements in
      functioning and reduction of physical symptoms from conversion disorder even for
      very severe cases. Hypnotherapy, cognitive behavioral therapy, and inpatient
      multidisciplinary treatment with intensive physiotherapy for severe cases have
      the most evidence to support reduction of symptoms. Components of treatment for
      conversion disorder overlap with treatments for chronic pain and can be used
      together to produce therapeutic effects for both conditions. Treatment needs to
      be tailored for each individual's specific symptoms.

PMID- 28434124
TI  - Comparative outcome of PFNA, Gamma nails, PCCP, Medoff plate, LISS and dynamic
      hip screws for fixation in elderly trochanteric fractures: a systematic review
      and network meta-analysis of randomized controlled trials.
AB  - The ideal implant for the treatment of an unstable intertrochanteric femoral
      fracture is still a matter of discussion. The aim of this systematic review is to
      conduct a network meta-analysis of randomized controlled trials (RCTs) comparing
      clinical outcomes between dynamic hip screws (DHS), Medoff sliding plating,
      percutaneous compression plating (PCCP), proximal femoral nails (PFN), Gamma
      nails and less invasive stabilization system fixation in femoral trochanteric
      fractures in the elderly. These clinical outcomes consist of total intra
      operative time, intra-operative fluoroscopy time, intra-operative blood loss,
      blood component transfusion, length of hospital stay, postoperative general
      complications, wound complications, late complications and reoperation rates.
      This systematic review was conducted using PubMed and Scopus search engines for
      RCTs comparing clinical outcomes between treatments from inception to February
      22, 2015. Thirty-six of 785 studies identified were eligible. Compared to the
      other implants, PCCP showed the lowest total operative time and units of blood
      transfusion with an unstandardized mean difference (UMD) of 29.27 min (95% CI
      5.24, 53.50) and 0.89 units (95% CI 0.52, 1.25). The lowest incidence of general
      complications, wound complications and late complications of PCCP was 0.09 (95%
      CI 0.04, 0.18), 0.01 (95% CI 0.01, 0.04) and 0.05 (95% CI 0.02, 0.11),
      respectively, when compared to others. The lowest fluoroscopic time was with DHS
      with an UMD of 0.24 min (95% CI 0.16, 0.32), whereas the lowest blood loss and
      shortest hospital stay were with PFN with an UMD of 233.61 ml of blood loss (95%
      CI 153.17, 314.04) and 7.23 days of hospital stay (95% CI 7.15, 7.31) when
      compared to all other fixation methods. Reoperation rates of all implants had no
      statistically significant difference. The network meta-analysis suggested that
      fixation with PCCP significantly shortens operative time and decreases the units
      of blood transfusion required, while also lowering risks of general
      complications, wound complications and late complications when compared to
      fixation. Use of PFN showed the least intra-operative blood loss and shortest
      hospital stay. Multiple active treatment comparisons indicate that PCCP fixation
      in trochanteric fractures in the elderly is the treatment of choice in terms of
      intra-operative outcomes and postoperative complications.

PMID- 28434125
TI  - Kidney morphological parameters measured using noncontrast-enhanced steady-state
      free precession MRI with spatially selective inversion recovery pulse correlate
      with eGFR in patients with advanced CKD.
AB  - BACKGROUND: It is well known that atrophic renal changes are associated with
      chronic kidney disease (CKD) progression, but conventional diagnostic imaging
      methods such as noncontrast-enhanced computed tomography and magnetic resonance
      imaging (MRI) have been insufficient for precisely assessing kidney function
      because they cannot clearly distinguish between the medulla and cortex. Hence,
      here we used noncontrast-enhanced steady-state free precession (SSFP) MRI with a
      spatially selective inversion recovery (IR) pulse to improve visibility for renal
      corticomedullary differentiation and evaluated the association between
      morphological parameters and kidney function in patients with CKD. METHODS:
      Kidney corticomedullary contrast ratio, cortical and medullary areas, and minimal
      cortical thickness of 107 patients with CKD G1-G5 were measured using SSFP MRI
      with a spatially selective IR pulse and the association between these
      morphological parameters and kidney function were evaluated. RESULTS:
      Corticomedullary contrast ratio was significantly improved on SSFP MRI compared
      with conventional in-phase T1-weighted gradient-echo MRI and positively
      correlated with estimated glomerular filtration ratio (eGFR), raw eGFR, and 24-h
      creatinine clearance. The medullary and cortical areas and minimal cortical
      thickness also positively correlated with those of kidney functional markers and
      the age. In patients with CKD and diabetes mellitus (DM), the correlation
      coefficients between raw eGFR and morphological parameters were higher than those
      in patients without DM, while minimal cortical thickness was larger in CKD
      patients with DM with a raw eGFR >= 45 mL/min. CONCLUSION: Kidney morphological
      parameters measured with SSFP MRI were clearly correlated with kidney function in
      patients with CKD, including those with advanced kidney dysfunction.

PMID- 28434126
TI  - Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte
      depletion.
AB  - BACKGROUND: Rituximab is effective against complicated childhood steroid
      dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell)
      depletion is strongly correlated with persistent remission, relapse rarely
      occurring during B-cell depletion; however, we have encountered several such
      patients. METHODS: We retrospectively analyzed the characteristics and clinical
      course of 82 patients with SDNS treated with rituximab from January 2007 to
      December 2012 in our institution. RESULTS: Six of 82 patients (7.3%) had relapses
      during B-cell depletion after receiving rituximab (relapsed group). The remaining
      76 patients did not have relapses during B-cell depletion (non-relapsed group).
      The median time to initial relapse during B-cell depletion was 85 days after
      receiving rituximab, which is significantly shorter than in the non-relapsed
      group (410 days, p = 0.0003). The median annual numbers of relapses after
      receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups,
      respectively (p < 0.0001). Five patients in the relapsed group also had a total
      of 10 relapses after B-cell recovery; their median time from B-cell recovery to
      initial relapse was significantly shorter than in the non-relapsed group (31 vs.
      161 days, p = 0.014). Number of relapses before rituximab, history of steroid
      resistance, onset age, previous treatment, time to ceasing steroids after
      rituximab, and duration of B-cell depletion did not differ between the two
      groups. CONCLUSION: Relapse during B-cell depletion after receiving rituximab
      suggests that various pathophysiological mechanisms play a part in childhood
      nephrotic syndrome.

PMID- 28434127
TI  - Intranasal vitamin A is beneficial in post-infectious olfactory loss.
AB  - Vitamin A plays a decisive role in the regeneration of olfactory receptor
      neurons. In this retrospective study we investigated the effectiveness of topical
      vitamin A in patients with post-infectious and posttraumatic smell disorders.
      Retrospective cohort. A total of 170 patients (age range 18-70 years, mean age 52
      years) participated. Forty-six patients were treated with smell training only.
      The remaining 124 patients received smell training and topical vitamin A.
      Olfactory function was assessed using the Sniffin' Sticks test kit, a validated
      technique to measure odor thresholds, discrimination and identification. The
      duration of olfactory training was 12 weeks. In patients receiving vitamin A,
      this was applied topically (head back position) at a dose of 10,000 IU/day for 8
      weeks. Follow-up testing was performed approximately 10 months after the first
      assessment. Thirty-seven per cent of all post-infectious patients treated with
      vitamin A exhibited clinical improvement, whereas only 23% improved in controls.
      Using a Chi-square test, this was a significant result (chi 2 = 7.06, df = 2, p =
      0.03). In addition, when comparing change in score after treatment, olfactory
      training + vitamin A produced significantly greater improvement compared with
      training alone, in discrimination score for all patients (1.4 points, p = 0.008),
      and in threshold and discrimination in the post-infectious group (1.6 points, p =
      0.01 and 1.4 points, p = 0.04, respectively). Intranasal vitamin A at a dose of
      10,000 IU per day for 2 months may be useful in the treatment of post-infectious
      olfactory loss. Further work with prospective, placebo-controlled studies is
      required to confirm these findings.

PMID- 28434128
TI  - Aspects on the history of transmission and favor of distribution of viruses by
      iatrogenic action: perhaps an example of a paradigm of the worldwide spread of
      HIV.
AB  - Transmission of infectious agents might be associated with iatrogenic actions of
      charitable help in health care. An example is the vaccination against yellow
      fever in USA that transmitted hepatitis B virus. Another example is injections of
      praziquantel for treatment and cure of schistosomiasis in Central and Northern
      Africa, with a focus in Egypt that has spread hepatitis C virus. There is no
      indication that human T-lymphotropic virus type 1 was spread by injection
      treatment for African trypanosomiasis, syphilis and treponematosis, but these
      treatments might have contributed to the early spread of human immunodeficiency
      virus type 1 (HIV-1) in Central Africa. Slave trade contributed as well to the
      spread of viruses from Africa to the Americas; it was stopped in 1850. Until that
      date HIV-1 was not transported to the Americas. By analysis of nucleic acid
      sequence data it can be concluded that the continental spread of HCV and HIV-1
      might have started around 1920 with an exponential phase from 1940 to 1970.
      Further iatrogenic actions that promoted the spread of HCV and HIV-1 might be
      vaccinations to prevent deadly diseases. The successful vaccination was followed
      by diminution of the infectious agent in the population such as small pox, yellow
      fever and measles. Measurements to reduce the spread of plague and cholera were
      further benefits increasing survival of diseased subjects in a population. Thus,
      the reduction of exposure to deadly infectious agents might have given a chance
      to HIV-1 infected subjects to survive and for HIV-1 to be distributed around the
      world starting from Central Africa in the 1950s.

PMID- 28434129
TI  - Phage-displayed peptides that mimic epitopes of hepatitis E virus capsid.
AB  - Hepatitis E is an emerging zoonotic infection of increasing public health threat
      for the UK, especially for immunosuppressed individuals. A human recombinant
      vaccine has been licensed only in China and is not clear whether it protects
      against hepatitis E virus (HEV) genotype 3, the most prevalent in Europe. The aim
      of this study was to use phage display technology as a tool to identify peptides
      that mimic epitopes of HEV capsid (mimotopes). We identified putative linear and
      conformational mimotopes using sera from Scottish blood donors that have the
      immunological imprint of past HEV infection. Four mimotopes did not have homology
      with the primary sequence of HEV ORF2 capsid but competed effectively with a
      commercial HEV antigen for binding to anti-HEV reference serum. When the
      reactivity profile of each mimotope was compared with Wantai HEV-IgG ELISA, the
      most sensitive HEV immunoassay, mimotopes showed 95.2-100% sensitivity while the
      specificity ranged from 81.5 to 95.8%. PepSurf algorithm was used to map affinity
      selected peptides onto the ORF2 crystal structure of HEV genotype 3, which
      predicted that these four mimototopes are clustered in the P domain of ORF2
      capsid, near conformational epitopes of anti-HEV neutralising monoclonal
      antibodies. These HEV mimotopes may have potential applications in the design of
      structural vaccines and the development of new diagnostic tests.

PMID- 28434130
TI  - Characterization of extracellular membrane vesicles of an Antarctic bacterium,
      Shewanella livingstonensis Ac10, and their enhanced production by alteration of
      phospholipid composition.
AB  - A cold-adapted bacterium, Shewanella livingstonensis Ac10, which produces
      eicosapentaenoic acid (EPA) as a component of its membrane phospholipids, is
      useful as a model to study the function of EPA and as a host for heterologous
      production of thermolabile proteins at low temperatures. In this study, we
      characterized extracellular membrane vesicles (EMVs) of this bacterium to examine
      the involvement of EPA in the biogenesis of EMVs and for the future application
      of EMVs to extracellular protein production. We found that this strain produced
      EMVs from the cell surface. Cryo-electron microscopic observation showed that the
      majority of the EMVs had a single-bilayer structure with an average diameter of
      110 nm, though EMVs with double-bilayer membranes and other diverse structures
      were also observed. Quantitative analysis demonstrated that the EMV production
      was significantly increased (3-5 fold) by the depletion of EPA-containing
      phospholipids. The lack of EPA also altered the protein composition of EMVs. In
      particular, incorporation of one of the cold-inducible outer membrane proteins,
      OmpC176, was significantly increased in EMVs after the depletion of EPA. These
      results provide a basis for the construction of an EMV-based, low-temperature
      protein production system and show the involvement of EPA in the regulation of
      EMV biogenesis.

PMID- 28434131
TI  - Knowing How and Knowing Why: testing the effect of instruction designed for
      cognitive integration on procedural skills transfer.
AB  - Transfer is a desired outcome of simulation-based training, yet evidence for how
      instructional design features promote transfer is lacking. In clinical reasoning,
      transfer is improved when trainees experience instruction integrating basic
      science explanations with clinical signs and symptoms. To test whether integrated
      instruction has similar effects in procedural skills (i.e., psychomotor skills)
      training, we studied the impact of instruction that integrates conceptual (why)
      and procedural (how) knowledge on the retention and transfer of simulation-based
      lumbar puncture (LP) skill. Medical students (N = 30) were randomized into two
      groups that accessed different instructional videos during a 60-min self
      regulated training session. An unintegrated video provided procedural How
      instruction via step-by-step demonstrations of LP, and an integrated video
      provided the same How instruction with integrated conceptual Why explanations
      (e.g., anatomy) for key steps. Two blinded raters scored post-test, retention,
      and transfer performances using a global rating scale. Participants also
      completed written procedural and conceptual knowledge tests. We used simple
      mediation regression analyses to assess the total and indirect effects (mediated
      by conceptual knowledge) of integrated instruction on retention and transfer.
      Integrated instruction was associated with improved conceptual (p < .001) but not
      procedural knowledge test scores (p = .11). We found no total effect of group (p
      > .05). We did find a positive indirect group effect on skill retention (B ab  =
      .93, p < .05) and transfer (B ab  = .59, p < .05), mediated through participants
      improved conceptual knowledge. Integrated instruction may improve trainees' skill
      retention and transfer through gains in conceptual knowledge. Such integrated
      instruction may be an instructional design feature for simulation-based training
      aimed at improving transfer outcomes.

PMID- 28434132
TI  - Water regulation: a Sword of Damocles for migratory waterbirds in China?

PMID- 28434133
TI  - Stiripentol in the Management of Epilepsy.
AB  - Stiripentol is a structurally unique antiepileptic drug that has several possible
      mechanisms of action, including diverse effects on the gamma-aminobutyric acid
      (GABA)-A receptor and novel inhibition of lactate dehydrogenase. Because of its
      inhibition of several cytochrome P450 enzymes, it has extensive pharmacokinetic
      interactions, which often necessitates reduction in doses of certain co
      therapies, particularly clobazam. Stiripentol also has a neuroprotective action,
      by reducing calcium-mediated neurotoxicity. Evidence of its efficacy is most
      robust for Dravet syndrome, where stiripentol added to clobazam and valproic acid
      reduces seizure frequency and severity in the majority of cases. Small case
      series have also suggested benefit for malignant migrating partial seizures in
      infancy, super-refractory status epilepticus, and intractable focal epilepsy,
      although larger prospective studies are needed in these disorders.

PMID- 28434135
TI  - Son Preference of Immigrants to the United States: Data from U.S. Birth
      Certificates, 2004-2013.
AB  - Son preference has existed for centuries in many cultures and societies. In some
      Asian countries, including China and India, the sex ratio at birth (SRB, number
      of male infants divided by number of female infants times 100) is elevated above
      the worldwide biological norm of about 105. We investigate whether this ratio is
      elevated in the U.S. for immigrant women. We analyze U.S. birth certificates for
      2004-2013 and categorize births by mother's and father's race/ethnicity; mother's
      place of birth, and birth order of the child. The SRB is elevated for two groups
      of women: Chinese women born in China for children of birth order 2 and higher,
      and Indian women born in India for children of birth order 3 and higher. The SRB
      is not elevated for Chinese and Indian women born in the U.S., nor for Mexican
      women, Black women, nor White women, regardless of place of birth. The
      race/ethnicity of the child's father does not appear to be a strong factor in the
      SRB. In the early twenty-first century the elevated SRB for Chinese and Indian
      women born in China and India respectively suggests sex selection for higher
      order births in the U.S.

PMID- 28434134
TI  - Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic
      Review and Meta-Analysis.
AB  - INTRODUCTION: Lamotrigine is used in pregnancy to control epilepsy and mood
      disorders. The reproductive safety of this widely used drug remains undefined and
      may represent a significant public health concern. OBJECTIVE: We aimed to perform
      a systematic review and meta-analysis of existing knowledge related to
      malformation rates and maternal-neonatal outcomes after in utero exposure to
      monotherapy with lamotrigine. METHODS: Relevant studies were identified through
      systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid),
      and Web of Science (Thomson Reuters) from database inception to July 2016; no
      language or date restrictions were applied. All publications of clinically
      relevant outcomes of pregnancies following in utero exposure to lamotrigine were
      included in this systematic review and meta-analysis. RESULTS: A total of 21
      studies describing immediate pregnancy outcomes and rates of congenital
      malformations fulfilled the inclusion criteria. Compared with disease-matched
      controls (n = 1412, total number of patients) and healthy controls (n = 774,571,
      total number of patients), in utero exposure to lamotrigine monotherapy was found
      to be associated with significantly decreased rates of inborn defects (odds ratio
      [OR] 1.15; 95% confidence interval [CI] 0.62-2.16 and OR 1.25; 95% CI 0.89-1.74,
      respectively). Rates of miscarriages, stillbirths, preterm deliveries, and small
      for gestational age (SGA) neonates were not found to have been increased after in
      utero exposure to LTG compared to the general population. Similarly, in utero
      exposure to lamotrigine monotherapy was not found to be associated with increased
      rates of inborn defects compared with in utero exposure to carbamazepine, and
      lamotrigine was found to be statistically significantly less teratogenic than
      valproic acid (n = 12,958 and 10,748; OR 0.84; 95% CI 0.68-1.03 and OR 0.32; 95%
      CI 0.26-0.39, respectively). CONCLUSION: No association was found between
      prenatal lamotrigine monotherapy and increased rates of birth defects and other
      explored variables related to adverse pregnancy outcomes.

PMID- 28434136
TI  - Facial expressions and speech acts: experimental evidences on the role of the
      upper face as an illocutionary force indicating device in language comprehension.
AB  - Language scientists have broadly addressed the problem of explaining how language
      users recognize the kind of speech act performed by a speaker uttering a sentence
      in a particular context. They have done so by investigating the role played by
      the illocutionary force indicating devices (IFIDs), i.e., all linguistic elements
      that indicate the illocutionary force of an utterance. The present work takes a
      first step in the direction of an experimental investigation of non-verbal IFIDs
      because it investigates the role played by facial expressions and, in particular,
      of upper-face action units (AUs) in the comprehension of three basic types of
      illocutionary force: assertions, questions, and orders. The results from a pilot
      experiment on production and two comprehension experiments showed that (1)
      certain upper-face AUs seem to constitute non-verbal signals that contribute to
      the understanding of the illocutionary force of questions and orders; (2)
      assertions are not expected to be marked by any upper-face AU; (3) some upper
      face AUs can be associated, with different degrees of compatibility, with both
      questions and orders.

PMID- 28434137
TI  - Cholesterol Hydroperoxide Generation, Translocation, and Reductive Turnover in
      Biological Systems.
AB  - Cholesterol is like other unsaturated lipids in being susceptible to peroxidative
      degradation upon exposure to strong oxidants like hydroxyl radical or
      peroxynitrite generated under conditions of oxidative stress. In the eukaryotic
      cell plasma membrane, where most of the cellular cholesterol resides,
      peroxidation leads to membrane structural and functional damage from which
      pathological states may arise. In low density lipoprotein, cholesterol and
      phospholipid peroxidation have long been associated with atherogenesis. Among the
      many intermediates/products of cholesterol oxidation, hydroperoxide species
      (ChOOHs) have a number of different fates and deserve special attention. These
      fates include (a) damage-enhancement via iron-catalyzed one-electron reduction,
      (b) damage containment via two-electron reduction, and (c) inter-membrane, inter
      lipoprotein, and membrane-lipoprotein translocation, which allows dissemination
      of one-electron damage or off-site suppression thereof depending on antioxidant
      location and capacity. In addition, ChOOHs can serve as reliable and conveniently
      detected mechanistic reporters of free radical-mediated reactions vs. non-radical
      (e.g., singlet oxygen)-mediated reactions. Iron-stimulated peroxidation of
      cholesterol and other lipids underlies a newly discovered form of regulated cell
      death called ferroptosis. These and other deleterious consequences of radical
      mediated lipid peroxidation will be discussed in this review.

PMID- 28434138
TI  - Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced
      Thromboembolism.
AB  - Cerebral tissue oxygenation (oxygen tension, pO2) is a critical parameter that is
      closely linked to brain metabolism, function, and pathophysiology. In this work,
      we have used electron paramagnetic resonance oximetry with a deep-tissue multi
      site oxygen-sensing probe, called implantable resonator, to monitor temporal
      changes in cerebral pO2 simultaneously at four sites in a rabbit model of
      ischemic stroke induced by embolic clot. The pO2 values in healthy brain were not
      significantly different among the four sites measured over a period of 4 weeks.
      During exposure to 15% O2 (hypoxia), a sudden and significant decrease in pO2 was
      observed in all four sites. On the other hand, brief exposure to breathing
      carbogen gas (95% O2 + 5% CO2) showed a significant increase in the cerebral pO2
      from baseline value. During ischemic stroke, induced by embolic clot in the left
      brain, a significant decline in the pO2 of the left cortex (ischemic core) was
      observed without any change in the contralateral sites. While the pO2 in the non
      infarct regions returned to baseline at 24-h post-stroke, pO2 in the infarct core
      was consistently lower compared to the baseline and other regions of the brain.
      The results demonstrated that electron paramagnetic resonance oximetry with the
      implantable resonator can repeatedly and simultaneously report temporal changes
      in cerebral pO2 at multiple sites. This oximetry approach can be used to develop
      interventions to rescue hypoxic/ischemic tissue by modulating cerebral pO2 during
      hypoxic and stroke injury.

PMID- 28434139
TI  - Neurological manifestations of atypical celiac disease in childhood.
AB  - Various typical and atypical neurological manifestations can be seen as the
      initial symptoms of celiac disease (CD). We suggest that gluten toxicity is the
      most suspicious triggering risk factor for probable pathophysiological pathways
      of neurological involvement in atypical CD. The medical charts of 117 patients
      diagnosed with atypical CD were retrieved from a tertiary center in Ankara,
      Turkey. Eight patients reported as having neurologic manifestations as initiating
      symptoms were evaluated in detail. The initial neurological manifestations of CD
      in our study included atypical absence, which was reported first in this study,
      generalized tonic-clonic seizures, complex partial seizures, severe axial
      hypotonia and down phenotype, multifocal leukoencephalopathy, mild optic
      neuritis, attention deficit hyperactivity disorder, and short duration headaches.
      Seizures mostly emphasizing atypical absence could be the initial presentation
      manifestation of CD, first described in this literature. Gluten toxicity could be
      one of the most powerful triggering factors for developing epilepsy in CD.
      Learning disorders such as attention deficit hyperactivity disorder, short
      duration headaches, mild optic neuritis, encephalopathy, and DS could also be the
      initial neurological manifestations of atypical CD. A gluten-restricted diet may
      improve neurological complaints, epileptic discharges, and neuropsychiatric
      symptoms. All we found may be a small part of the full range of neurological
      disorders of unknown origin related to CD. Clinical suspicion should be the rule
      for accurate diagnosis of the disease.

PMID- 28434140
TI  - Radiation therapy for recurrent cardiac undifferentiated pleomorphic sarcoma
      after three operations.
AB  - We report the case of a 57-year-old female suffering from recurrent malignant
      undifferentiated pleomorphic sarcoma of the left atrium. Metastasis to the
      posterior mediastinum was detected upon first presentation. Incomplete resections
      were carried out twice before mitral valve replacement was finally performed. The
      tumor recurred 16 months later and was treated with radiation therapy, which has
      proved to be effective in bringing about tumor regression for 2 years, to date.
      The patient has survived for 7 years since the first surgery.

PMID- 28434141
TI  - Prescription Appropriateness of Cyproterone Acetate/Ethinylestradiol in Primary
      Care: A Population-Based Study in Italy.
AB  - BACKGROUND AND OBJECTIVE: We evaluated the prescription appropriateness of
      cyproterone acetate in combination with ethinylestradiol (CPA/EE) in a primary
      care setting before and after the 2013 European Medicines Agency's (EMA)
      recommendation relating to the risk profile of CPA/EE. METHODS: Data were
      obtained from the Health Search IMS Health Longitudinal Patient Database (HSD).
      We compared the results from 2011 to 2012 with the results of 2014, namely before
      and after the 2013 EMA recommendation, and investigated the burden of concurrent
      use of CPA/EE and other hormonal contraceptives (HCs) and the reported indication
      at the time of CPA/EE prescription. RESULTS: Overall, 1189 new users of CPA/EE
      were identified: 495 in 2011, 446 in 2012, and 261 in 2014. Concomitant use of
      CPA/EE and other HCs was found in 1% of cases in 2011-2012 and 2% of cases in
      2014, while potential concomitant use was observed in 4% of cases in 2011 and 2%
      of cases in 2012 and 2014. A recent (within 365 days) diagnosis of any
      hyperandrogenic condition was detected in 22 and 24% of CPA/EE users in 2011 and
      2012, respectively, and in 24% of cases in 2014. The percentage of CPA/EE users
      with a recent acne diagnosis and/or treatment was 19, 21, and 18% in 2011, 2012,
      and 2014, respectively. CONCLUSIONS: Apart from an overall reduction in CPA/EE
      prescriptions in the HSD, no substantial difference was found in terms of the
      proportions of patients diagnosed with acne or other hyperandrogenic conditions
      and/or potential concomitant use of HCs before and after the EMA recommendation.

PMID- 28434142
TI  - Cancer Genetic Counseling and Testing in an Era of Rapid Change.
AB  - The impacts of the Association for Molecular Pathology vs. Myriad Supreme Court
      decision regarding patenting DNA segments and multi-gene testing on cancer
      genetic counseling practice have not been well described. We aimed to assess
      genetic counselors' perceptions of how their genetic testing-related practices
      for hereditary breast and/or ovarian cancer (HBOC) changed after these events.
      One-hundred fifty-two genetic counselors from the National Society of Genetic
      Counselors Cancer Special Interest Group completed an anonymous, online, mixed
      methods survey in November 2013. The survey presented four hypothetical patients
      and asked about changes in testing practice. Across the vignettes, a majority of
      participants reported specific changes in testing decisions following Association
      for Molecular Pathology vs. Myriad and availability of multi-gene testing. Ninety
      three percent of participants reported changing the types of first- and second
      line tests they order for HBOC; the degree of change varied geographically.
      Qualitative analysis indicated that some counselors have altered the counseling
      session content, trading depth of information for breadth and spending more time
      counseling about uncertainty. This study shows that cancer genetic counselors are
      adapting quickly to genetic testing changes, but with wide variability. Findings
      suggest future research to elucidate clinicians' and patients' preferences for
      guidance on the clinical implementation of next-generation sequencing.

PMID- 28434143
TI  - The mTOR Signaling Pathway in Myocardial Dysfunction in Type 2 Diabetes Mellitus.
AB  - PURPOSE OF REVIEW: T2DM (type 2 diabetes mellitus) is a risk factor for heart
      failure. The mTOR (mechanistic target of rapamycin) is a key mediator of the
      insulin signaling pathway. We will discuss the role of mTOR in myocardial
      dysfunction in T2DM. RECENT FINDINGS: In T2DM, chronically activated mTOR induces
      multiple pathological events, including a negative feedback loop that suppresses
      IRS (insulin receptor substrate)-1. While short-term treatment with rapamycin, an
      mTOR inhibitor, is a promising strategy for cardiac diseases such as acute
      myocardial infarction and cardiac hypertrophy in T2DM, there are many concerns
      about chronic usage of rapamycin. Two mTOR complexes, mTORC1 and mTORC2, affect
      many molecules and processes via distinct signaling pathways that regulate
      cardiomyocyte function and survival. Understanding mechanisms underlying mTOR
      mediated pathophysiological features in the heart is essential for developing
      effective therapies for cardiac diseases in the context of T2DM.

PMID- 28434144
TI  - Peer Coaching Interventions for Parents of Children with Type 1 Diabetes.
AB  - PURPOSE OF REVIEW: Peer support is a promising model of providing psychosocial
      support to parents of children with type 1 diabetes. This review seeks to discuss
      the findings of the existing literature in peer coaching as it relates to parents
      and diabetes as well as to identify gaps in knowledge for future intervention
      development and implementation. RECENT FINDINGS: Peer support programs vary
      widely with regard to recruitment, training, and delivery protocols. Across most
      programs, ongoing support and supervision are provided to peer coaches. Despite
      inconsistent effects on psychosocial and child health outcomes, parent coaching
      is consistently a highly acceptable and feasible intervention with parents of
      children with T1D. Current evidence supports use of parent coaching as part of a
      multicomponent intervention or program to increase patient satisfaction, but more
      research is needed to determine if it can stand alone as an active mechanism for
      behavior change. The use of peer coach interventions for parents of young
      children with diabetes is feasible to implement and highly acceptable. However,
      more research is needed to understand the enduring impact for target parents and
      peer coaches alike, as well as impact on child outcomes.

PMID- 28434145
TI  - mTORC1 signaling in hepatic lipid metabolism.
AB  - The mechanistic target of rapamycin (mTOR) signaling pathway regulates many
      metabolic and physiological processes in different organs or tissues.
      Dysregulation of mTOR signaling has been implicated in many human diseases
      including obesity, diabetes, cancer, fatty liver diseases, and neuronal
      disorders. Here we review recent progress in understanding how mTORC1 (mTOR
      complex 1) signaling regulates lipid metabolism in the liver.

PMID- 28434146
TI  - Differential regulation of H3S10 phosphorylation, mitosis progression and cell
      fate by Aurora Kinase B and C in mouse preimplantation embryos.
AB  - Coordination of cell division and cell fate is crucial for the successful
      development of mammalian early embryos. Aurora kinases are evolutionarily
      conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B
      (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically
      expressed in gametes and preimplantation embryos. We found that increasing AurkC
      level in one blastomere of the 2-cell embryo accelerated cell division and
      decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite
      effect. The kinase domains of AurkB and AurkC were responsible for their
      different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate
      metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP)
      and fluorescence decay after photoactivation assay, we found that AurkB
      overexpression reduced Oct4 retention in the nucleus. Finally, we show that
      blastomeres with higher AurkC level elevated pluripotency gene expression, which
      were inclined to enter the inner cell mass lineage and subsequently contributed
      to the embryo proper. Collectively, our results are the first demonstration that
      the activity of mitotic kinases can influence cell fate decisions in mammalian
      preimplantation embryos and have important implications to assisted reproduction.

PMID- 28434147
TI  - Increasing the safety and efficacy of chimeric antigen receptor T cell therapy.
AB  - Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment
      that has recently been undergoing rapid development. However, there are still
      some major challenges, including precise tumor targeting to avoid off-target or
      "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to
      solid tumors and T cell proliferation and persistence across the physical and
      biochemical barriers of solid tumors. In this review, we focus on the primary
      challenges and strategies to design safe and effective CAR T cells, including
      using novel cutting-edge technologies for CAR and vector designs to increase both
      the safety and efficacy, further T cell modification to overcome the tumor
      associated immune suppression, and using gene editing technologies to generate
      universal CAR T cells. All these efforts promote the development and evolution of
      CAR T cell therapy and move toward our ultimate goal-curing cancer with high
      safety, high efficacy, and low cost.

PMID- 28434148
TI  - Advancing chimeric antigen receptor T cell therapy with CRISPR/Cas9.
AB  - The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is
      triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated
      great potential for genetic manipulation. In this review, we discuss the current
      development of CRISPR/Cas9 technologies for therapeutic applications, especially
      chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different
      methods used to facilitate efficient CRISPR delivery and gene editing in T cells
      are compared. The potential of genetic manipulation using CRISPR/Cas9 system to
      generate universal CAR T cells and potent T cells that are resistant to
      exhaustion and inhibition is explored. We also address the safety concerns
      associated with the use of CRISPR/Cas9 gene editing and provide potential
      solutions and future directions of CRISPR application in the field of CAR T cell
      immunotherapy. As an integration-free gene insertion method, CRISPR/Cas9 holds
      great promise as an efficient gene knock-in platform. Given the tremendous
      progress that has been made in the past few years, we believe that the
      CRISPR/Cas9 technology holds immense promise for advancing immunotherapy.

PMID- 28434149
TI  - Solvent-dependent transformation of aflatoxin B1 in soil.
AB  - To date, all studies of aflatoxin B1 (AFB1) transformation in soil or in purified
      mineral systems have identified aflatoxins B2 (AFB2) and G2 (AFG2) as the primary
      transformation products. However, identification in these studies was made using
      thin layer chromatography which has relatively low resolution, and these studies
      did not identify a viable mechanism by which such transformations would occur.
      Further, the use of methanol as the solvent delivery vehicle in these studies may
      have contributed to formation of artifactual transformation products. In this
      study, we investigated the role of the solvent vehicle in the transformation of
      AFB1 in soil. To do this, we spiked soils with AFB1 dissolved in water (93:7,
      water/methanol) or methanol and used HPLC-UV and HPLC-MS to identify the
      transformation products. Contrasting previous published reports, we did not
      detect AFB2 or AFG2. In an aqueous-soil environment, we identified aflatoxin B2a
      (AFB2a) as the single major transformation product. We propose that AFB2a is
      formed from hydrolysis of AFB1 with the soil acting as an acid catalyst.
      Alternatively, when methanol was used, we identified methoxy aflatoxin species
      likely formed via acid-catalyzed addition of methanol to AFB1. These results
      suggest that where soil moisture is adequate, AFB1 is hydrolyzed to AFB2a and
      that reactive organic solvents should be avoided when replicating natural
      conditions to study the fate of AFB1 in soil.

PMID- 28434150
TI  - High-sensitive troponin T assay can predict anthracycline- and trastuzumab
      induced cardiotoxicity in breast cancer patients.
AB  - BACKGROUND: Trastuzumab following anthracycline causes cardiotoxicity in up to
      28% of patients. Although the cardiotoxicity is often irreversible once cardiac
      dysfunction is detected, the early predictor has not been established yet.
      METHODS: We prospectively observed breast cancer patients treated with
      anthracycline or trastuzumab at Tonan Hospital. All patients underwent
      echocardiography and blood sampling at baseline, and every three months during
      chemotherapy. Cardiotoxicity was defined as a decline in left ventricular
      ejection fraction >10% points. RESULTS: Of 40 patients, 34 patients (85%) were
      treated with anthracycline (epirubicin), 18 (45%) with trastuzumab, and 12 (30%)
      with both agents. Cardiotoxicity was observed in four patients (10%), who were
      all treated with both agents. The absolute levels of high-sensitive troponin T
      (hs-TnT) were increased in all four patients with cardiotoxicity, and all the
      highest points were observed before or at the time of detection of
      cardiotoxicity. The highest level of hs-TnT was not significantly different in
      patients with and without cardiotoxicity. "Hs-TnT increment from baseline to the
      highest value" and "hs-TnT integration value above baseline" were significantly
      greater in patients with cardiotoxicity (0.039 vs. 0.007 ng/mL, P = 0.046, 0.113
      vs. 0.022 ng months/mL, P = 0.013, respectively). The integration value had 100%
      sensitivity and specificity with a cutoff level at 0.070 ng months/mL.
      CONCLUSIONS: Hs-TnT assay may be able to predict anthracycline- and trastuzumab
      induced cardiotoxicity in breast cancer patients, and the hs-TnT increment or hs
      TnT integration value above baseline was more reliable than the absolute value.

PMID- 28434151
TI  - CBF2A-CBF4B genomic region copy numbers alongside the circadian clock play key
      regulatory mechanisms driving expression of FR-H2 CBFs.
AB  - The C-Repeat Binding Factors (CBFs) are DNA-binding transcriptional activators
      that were identified using Arabidopsis thaliana. In barley, Hordeum vulgare, a
      cluster of CBF genes reside at FROST RESISTANCE-H2, one of two loci having major
      effects on winter-hardiness. FR-H2 was revealed in a population derived from the
      winter barley 'Nure' and the spring barley 'Tremois'. 'Nure' harbors two to three
      copies of CBF2A and CBF4B as a consequence of tandem iteration of the genomic
      region encompassing these genes whereas 'Tremois' harbors single copies, and
      these copy number differences are associated with their transcript level
      differences. Here we explore further the relationship between FR-H2 CBF gene copy
      number and transcript levels using 'Admire', a winter barley accumulating FR-H2
      CBF gene transcripts to very high levels, and a group of lines related to
      'Admire' through descent. DNA blot hybridization indicated the CBF2A-CBF4B
      genomic region is present in 7-8 copies in 'Admire' and is highly variable in
      copy number across the lines related to 'Admire'. At normal growth temperatures
      transcript levels of CBF12, CBF14, and CBF16 were higher in lines having greater
      CBF2A-CBF4B genomic region copy numbers than in lines having fewer copy numbers
      at peak expression level time points controlled by the circadian clock. Chromatin
      immunoprecipitation indicated CBF2 was at the CBF12 and CBF16 promoters at normal
      growth temperatures. These data support a scenario in which CBF2A-CBF4B genomic
      region copy numbers affect expression of other FR-H2 CBFs through a mechansim in
      which these other FR-H2 CBFs are activated by those in the copy number variable
      unit.

PMID- 28434152
TI  - Compression Garments and Recovery from Exercise: A Meta-Analysis.
AB  - BACKGROUND: Adequate recovery from exercise is essential to maintain performance
      throughout training and competition. While compression garments (CG) have been
      demonstrated to accelerate recovery, the literature is clouded by conflicting
      results and uncertainty over the optimal conditions of use. OBJECTIVES: A meta
      analysis was conducted to assess the effects of CG on the recovery of strength,
      power and endurance performance following an initial bout of resistance, running,
      or non-load-bearing endurance (metabolic) exercise. METHODS: Change-score data
      were extracted from 23 peer-reviewed studies on healthy participants. Recovery
      was quantified by converting into standardized mean effect sizes (ES) [+/-95%
      confidence interval (CI)]. The effects of time (0-2, 2-8, 24, >24 h), pressure
      (<15 vs. >=15 mmHg) and training status (trained vs. untrained) were also
      assessed. RESULTS: CG demonstrated small, very likely benefits [p < 0.001, ES =
      0.38 (95% CI 0.25, 0.51)], which were not influenced by pressure (p = 0.06) or
      training status (p = 0.64). Strength recovery was subject to greater benefits
      than other outcomes [p < 0.001, ES = 0.62 (95% CI 0.39, 0.84)], displaying large,
      very likely benefits at 2-8 h [p < 0.001, ES = 1.14 (95% CI 0.72, 1.56)] and >24
      h [p < 0.001, ES = 1.03 (95% CI 0.48, 1.57)]. Recovery from using CG was greatest
      following resistance exercise [p < 0.001, ES = 0.49 (95% CI 0.37, 0.61)],
      demonstrating the largest, very likely benefits at >24 h [p < 0.001, ES = 1.33
      (95% CI 0.80, 1.85)]. Recovery from metabolic exercise (p = 0.01) was
      significant, although large, very likely benefits emerged only for cycling
      performance at 24 h post-exercise [p = 0.01, ES = 1.05 (95% CI 0.25, 1.85)].
      CONCLUSION: The largest benefits resulting from CG were for strength recovery
      from 2 to 8 h and >24 h. Considering exercise modality, compression most
      effectively enhanced recovery from resistance exercise, particularly at time
      points >24 h. The use of CG would also be recommended to enhance next-day cycling
      performance. The benefits of CG in relation to applied pressures and participant
      training status are unclear and limited by the paucity of reported data.

PMID- 28434153
TI  - Machine learning-XGBoost analysis of language networks to classify patients with
      epilepsy.
AB  - Our goal was to apply a statistical approach to allow the identification of
      atypical language patterns and to differentiate patients with epilepsy from
      healthy subjects, based on their cerebral activity, as assessed by functional MRI
      (fMRI). Patients with focal epilepsy show reorganization or plasticity of brain
      networks involved in cognitive functions, inducing 'atypical' (compared to
      'typical' in healthy people) brain profiles. Moreover, some of these patients
      suffer from drug-resistant epilepsy, and they undergo surgery to stop seizures.
      The neurosurgeon should only remove the zone generating seizures and must
      preserve cognitive functions to avoid deficits. To preserve functions, one should
      know how they are represented in the patient's brain, which is in general
      different from that of healthy subjects. For this purpose, in the pre-surgical
      stage, robust and efficient methods are required to identify atypical from
      typical representations. Given the frequent location of regions generating
      seizures in the vicinity of language networks, one important function to be
      considered is language. The risk of language impairment after surgery is
      determined pre-surgically by mapping language networks. In clinical settings,
      cognitive mapping is classically performed with fMRI. The fMRI analyses allowing
      the identification of atypical patterns of language networks in patients are not
      sufficiently robust and require additional statistic approaches. In this study,
      we report the use of a statistical nonlinear machine learning classification, the
      Extreme Gradient Boosting (XGBoost) algorithm, to identify atypical patterns and
      classify 55 participants as healthy subjects or patients with epilepsy. XGBoost
      analyses were based on neurophysiological features in five language regions
      (three frontal and two temporal) in both hemispheres and activated with fMRI for
      a phonological (PHONO) and a semantic (SEM) language task. These features were
      combined into 135 cognitively plausible subsets and further submitted to
      selection and binary classification. Classification performance was scored with
      the Area Under the receiver operating characteristic curve (AUC). Our results
      showed that the subset SEM_LH BA_47-21 (left fronto-temporal activation induced
      by the SEM task) provided the best discrimination between the two groups (AUC of
      91 +/- 5%). The results are discussed in the framework of the current debates of
      language reorganization in focal epilepsy.

PMID- 28434154
TI  - Protective Effects of Cell-Free Supernatant and Live Lactic Acid Bacteria
      Isolated from Thai Pigs Against a Pandemic Strain of Porcine Epidemic Diarrhea
      Virus.
AB  - Porcine epidemic diarrhea virus (PEDV) is a coronavirus which causes severe
      diarrhea and fatal dehydration in piglets. In general, probiotic supplements
      could enhance recovery and protect piglets against enteric pathogens. Seven local
      lactic acid bacteria (LAB), (Ent. faecium 79N and 40N, Lact. plantarum 22F, 25F
      and 31F, Ped. acidilactici 72N and Ped. pentosaceus 77F) from pig feces were well
      characterized as high potential probiotics. Cell-free supernatants (CFS) and live
      LAB were evaluated for antiviral activities by co-incubation on Vero cells and
      challenged with a pandemic strain of PEDV isolated from pigs in Thailand. Cell
      survival and viral inhibition were determined by cytopathic effect (CPE)
      reduction assay and confirmed by immunofluorescence. At 1:16, CFS dilution (pH
      6.3-6.8) showed no cytotoxicity in Vero cells and was therefore used as the
      dilution for antiviral assays. The diluted CFS of all Lact. plantarum showed the
      antiviral effect against PEDV; however, the same antiviral effect could not be
      observed in Ent. faecium and Pediococcus strains. In competitive experiment, only
      live Lact. plantarum 25F and Ped. pentosaceus 77F showed CPE reduction in the
      viral infected cells to <50% observed field area. This study concluded that the
      CFS of all tested lactobacilli, and live Lact. plantarum (22F and 25F) and
      Pediococcus strains 72N and 77F could reduce infectivity of the pandemic strain
      of PEDV from pigs in Thailand on the target Vero cells.

PMID- 28434155
TI  - Nitrogen fertility and abiotic stresses management in cotton crop: a review.
AB  - This review outlines nitrogen (N) responses in crop production and potential
      management decisions to ameliorate abiotic stresses for better crop production. N
      is a primary constituent of the nucleotides and proteins that are essential for
      life. Production and application of N fertilizers consume huge amounts of energy,
      and excess is detrimental to the environment. Therefore, increasing plant N use
      efficiency (NUE) is important for the development of sustainable agriculture. NUE
      has a key role in crop yield and can be enhanced by controlling loss of
      fertilizers by application of humic acid and natural polymers (hydrogels), having
      high water-holding capacity which can improve plant performance under field
      conditions. Abiotic stresses such as waterlogging, drought, heat, and salinity
      are the major limitations for successful crop production. Therefore, integrated
      management approaches such as addition of aminoethoxyvinylglycine (AVG), the film
      antitranspirant (di-1-p-menthene and pinolene) nutrients, hydrogels, and
      phytohormones may provide novel approaches to improve plant tolerance against
      abiotic stress-induced damage. Moreover, for plant breeders and molecular
      biologists, it is a challenge to develop cotton cultivars that can tolerate plant
      abiotic stresses while having high potential NUE for the future.

PMID- 28434156
TI  - Paediatric sepsis: old wine in new bottles?

PMID- 28434157
TI  - General practitioner attitudes towards prescribing aspirin to carriers of Lynch
      Syndrome: findings from a national survey.
AB  - A dose non-inferiority study comparing 100 mg, 300 mg and 600 mg of aspirin for
      cancer prevention among Lynch Syndrome carriers is underway (Colorectal
      Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation
      of the findings, we investigated general practitioner (GP) attitudes towards
      aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6%
      response rate). Using a within-subjects design, GPs read a statement on harms and
      benefits of aspirin and indicated their willingness to prescribe aspirin at three
      doses (100 mg, 300 mg, 600 mg). Approximately two-thirds (70.8%) of GPs had heard
      of Lynch Syndrome or its associated names, and among those 46.7% were aware of
      the cancer preventive effects of aspirin among carriers. Two-thirds (68.1%) of
      GPs reported feeling comfortable discussing harms and benefits of aspirin with a
      Lynch Syndrome patient. Willingness to prescribe was 91.3% at 100 mg, and
      declined to 81.8% at 300 mg and 62.3% at 600 mg (p < 0.001). In multivariable
      analyses, willingness to prescribe (600 mg) was higher among GPs >=50 years (OR
      1.46, 95% CI 1.03-2.07), more experienced GPs (OR 1.50, 95% CI 1.10-2.04), GPs
      who were aware of the cancer preventive effects of aspirin (OR 1.58, 95% CI 1.20
      2.09), and those who reported seeing a Lynch Syndrome patient in practice (OR
      1.44, 95% CI 1.01-2.05, p = 0.045). GPs report limited awareness of Lynch
      Syndrome and the preventive effects of aspirin among carriers. To ensure the
      optimal dose identified in the CaPP3 trial is readily available to patients,
      prescribing guidance and strategies to educate GPs should be developed.

PMID- 28434158
TI  - Physical performance in newly diagnosed hypothyroidism: a pilot study.
AB  - OBJECTIVE: Hypothyroidism is complicated by neuromuscular symptoms (myalgias,
      slowness of movements, and tiredness) and signs (easy fatigability and cramps),
      which may have a negative impact on general well-being and quality of life. In a
      pilot, prospective, controlled study, we investigated the features of muscle
      dysfunction in hypothyroidism by disease questionnaire, biochemical measures, and
      physical performance tests. MATERIALS AND METHODS: Fifty-seven consecutive
      patients with newly diagnosed hypothyroidism were enrolled, 27 subclinical (S
      Hypo) and 30 overt (O-Hypo). A series of 30 euthyroid subjects, with similar
      demographic characteristics, served as controls. Patients were administered a
      short disease questionnaire and underwent laboratory exams and standardized
      physical tests, both at baseline and after restoration of biochemical
      euthyroidism. RESULTS: Compared to euthyroid controls, the O-Hypo group showed
      significantly higher prevalence of neuromuscular symptoms and significantly
      higher serum creatine phosphokinase (CPK) levels (p value < 0.0001). S-Hypo had
      slightly higher CPK levels and prevalence of neuromuscular symptoms than
      controls. Both S-Hypo and O-Hypo patients performed worse than controls in the
      six-minute walking test. Differences between patients and controls in handgrip
      strength test and timed chair standing test failed to reach statistical
      significance (although a trend was noticeable), possibly due to the small sample
      size. In O-Hypo, an inverse correlation was found between CPK levels and the
      handgrip strength test (p value < 0.001). Restoration of euthyroidism was
      associated with normalization of questionnaire responses, six-minute walking
      test, as well as serum CPK levels. CONCLUSION: In addition to neuromuscular
      symptoms, hypothyroidism is associated with abnormalities of physical
      performance. The six-minute walking test is the most valuable test to assess this
      aspect. In the pilot study, levothyroxine therapy could reverse muscle functional
      abnormalities.

PMID- 28434160
TI  - Repeated mild traumatic brain injuries is not associated with volumetric
      differences in former high school football players.
AB  - We investigated potential brain volumetric differences in a sample of former high
      school football players many years after these injuries. Forty community-dwelling
      males ages 40-65 who played high school football, but not college or professional
      sports, were recruited. The experimental group (n = 20) endorsed experiencing two
      or more mTBIs on an empirically validated mTBI assessment tool (median = 3, range
      = 2-15). The control group (n = 20) denied ever experiencing an mTBI.
      Participants completed a self-report index of current mTBI symptomatology and
      underwent high-resolution T1-weighted MRI scanning, which were analyzed using the
      Freesurfer software package. A priori regions of interest (ROIs) included total
      intracranial volume (ICV), total gray matter, total white matter, bilateral
      anterior cingulate cortex, bilateral hippocampi, and lateral ventricles. ROIs
      were corrected for head size using a normalization method that took ICV into
      account. Despite an adequate sample size and being matched on age, education,
      estimated premorbid IQ, current concussive symptomatology, there were no
      statistically significant volumetric group differences across all of the ROIs.
      These data suggest that multiple mTBIs from high school football may not be
      associated with measurable brain atrophy later in life. Accounting for the
      severity of injury and chronicity of sport exposure may be especially important
      when measuring long-term neuroanatomical differences.

PMID- 28434159
TI  - Decreased hemispheric connectivity and decreased intra- and inter- hemisphere
      asymmetry of resting state functional network connectivity in schizophrenia.
AB  - Many studies have shown that schizophrenia patients have aberrant functional
      network connectivity (FNC) among brain regions, suggesting schizophrenia
      manifests with significantly diminished (in majority of the cases) connectivity.
      Schizophrenia is also associated with a lack of hemispheric lateralization.
      Hoptman et al. (2012) reported lower inter-hemispheric connectivity in
      schizophrenia patients compared to controls using voxel-mirrored homotopic
      connectivity. In this study, we merge these two points of views together using a
      group independent component analysis (gICA)-based approach to generate hemisphere
      specific timecourses and calculate intra-hemisphere and inter-hemisphere FNC on a
      resting state fMRI dataset consisting of age- and gender-balanced 151
      schizophrenia patients and 163 healthy controls. We analyzed the group
      differences between patients and healthy controls in each type of FNC measures
      along with age and gender effects. The results reveal that FNC in schizophrenia
      patients shows less hemispheric asymmetry compared to that of the healthy
      controls. We also found a decrease in connectivity in all FNC types such as intra
      left (L_FNC), intra-right (R_FNC) and inter-hemisphere (Inter_FNC) in the
      schizophrenia patients relative to healthy controls, but general patterns of
      connectivity were preserved in patients. Analyses of age and gender effects
      yielded results similar to those reported in whole brain FNC studies.

PMID- 28434161
TI  - Can Valproic Acid Regulate Neurogenesis from Nestin+ Cells in the Adult Midbrain?
AB  - Degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc)
      causes the motor symptoms (e.g. tremor, muscle rigidity, bradykinesia, postural
      instability) of Parkinson's disease (PD). It is generally agreed that replacing
      these neurons will provide better motor symptom relief and fewer side effects
      than current pharmacotherapies. One potential approach to this is up-regulating
      endogenous DA neurogenesis in SNc. In the present study, we conducted
      bioinformatics analyses to identify signalling pathways that control expression
      of Pax6 and Msx1 genes, which have been identified as potentially important
      neurogenic regulators in the adult midbrain. From this Valproic acid (VPA) was
      identified as a regulator of these pathways, and we tested VPA for its ability to
      regulate midbrain neurogenesis in adult mice. VPA was infused directly into the
      midbrain of adult NesCreERT2/R26eYFP mice using osmotic pumps attached to
      implanted cannula. These mice enable permanent eYFP+ labelling of adult Nestin
      expressing neural precursor cells and their progeny/ontogeny. VPA did not affect
      the number of eYFP+ midbrain cells, but significantly reduced the number of
      Pax6+, Pax6+/NeuN+, eYFP+/NeuN+ and eYFP-/NeuN+ cells. However, this reduction in
      NeuN expression was probably via VPA's Histone de-acetylase inhibitory properties
      rather than reduced neuronal differentiation by eYFP + cells. We conclude that
      Pax6 and Msx1 are not viable targets for regulating neurogenesis in the adult
      midbrain.

PMID- 28434162
TI  - Isolation of Astrocytes Displaying Myofibroblast Properties and Present in
      Multiple Sclerosis Lesions.
AB  - A wide heterogeneity of lesions can affect the central nervous system (CNS). In
      all situations where neurons are damaged, including multiple sclerosis (MS), a
      common reactive astrocytosis is present. Sedimentation field-flow fractionation
      (SdFFF) was used to sort astrocyte subpopulations. After SdFFF elution, cells,
      prepared from rat newborn cortex, were cultured and analyzed by
      immunocytofluorescence for glial fibrillary acidic protein (GFAP) and alpha
      smooth muscle (SM) actin (a specific marker for myofibroblasts) expression. Cell
      contractile capacity was studied. Samples from patients with MS were also
      analyzed. Three main fractions (F1, F2, and F3) were isolated and compared with
      the total eluted population (TP). TP, F1, F2, and F3, contained respectively 74,
      96, 12, and 98% of GFAP expressing astrocytes. In F3, astrocytes only expressed
      GFAP while in F1, astrocytes expressed both GFAP and alpha-SM actin. In F2 and
      TP, alpha-SM actin expression was barely detected. F3-derived cells showed higher
      contractile capacities compared with F1-derived cells. In one specific case of MS
      known as Balo's concentric MS, astrocytes expressing both GFAP and alpha-SM actin
      were detected. Using SdFFF, a population of astrocytes presenting myofibroblast
      properties was isolated. This subpopulation of astrocytes was also observed in a
      MS sample suggesting that it could be involved in lesion formation and remodeling
      during CNS pathologies.

PMID- 28434163
TI  - Biomarkers of Epileptogenesis: The Focus on Glia and Cognitive Dysfunctions.
AB  - The need to find measures that reliably predict the onset of epilepsy after
      injurious events or how the patient will respond to anti-seizure drugs led to
      intensive pre-clinical and clinical research to discover non-invasive biomarkers
      that could increase the sensitivity of existing clinical indicators. The use of
      experimental models of epileptogenesis and of drug-resistance is instrumental to
      select the most promising approaches to explore such biomarkers in the pre
      clinical setting for further clinical validation. The approaches most frequently
      used to find clinically useful biomarkers of epileptogenesis include molecular
      brain imaging, EEG signal analysis and the measure of soluble molecules in
      biofluids which may reflect brain intrinsic events involved in epilepsy
      development. Among those, we focused our attention on proton magnetic resonance
      imaging (1H-MRS)-based analysis of astrocytic activation, and related blood
      biomarkers, since this cell population appears to be pivotally involved in
      various epileptogenesis processes triggered by differing insults. Moreover, we
      also investigated behavioral biomarkers by focusing on cognitive dysfunctions
      since this deficit represents a typical co-morbidity in epilepsy which may
      manifest even before the onset of spontaneous seizures. In this review article,
      we will report our recently published evidence supporting the utility of
      measuring astrocyte activation, the soluble molecules they release, and the
      associated cognitive deficits during epileptogenesis for early stratification of
      animals developing epilepsy. We will discuss the potential clinical translation
      of our findings for enriching the patient population in preventive clinical
      trials designed to study anti-epileptogenic treatments.

PMID- 28434164
TI  - Microglia Loss Contributes to the Development of Major Depression Induced by
      Different Types of Chronic Stresses.
AB  - Recently, the loss and dystrophy of hippocampal microglia induced by chronic
      unpredictable stress (CUS) has been reported to mediate the development of major
      depression in mice whose microglial cells were labeled with enhanced green
      fluorescent protein-conjuncted-CX3C receptor type 1. However, whether this
      happens in endogenous microglia with no genetic intervention remains unclear.
      Here, we addressed this issue in mice treated with different types of chronic
      stresses, including the CUS, chronic restraint stress (CRS) and chronic social
      defeat stress (CSDS). Results showed that the cellular numbers, process lengths,
      soma areas and activation markers of endogenous hippocampal but not cortical
      microglia, were markedly reduced by CUS, CRS and CSDS treatment. Administration
      of mice with two classical stimulators of microglia, lipopolysaccharide (LPS) or
      macrophage colony-stimulating factor (M-CSF), reversed the CUS-, CRS- and CSDS
      induced reductions in endogenous hippocampal microglial numbers, and also
      improved the CUS-, CRS- or CSDS-induced behavioral abnormalities, including the
      increases in the immobile time in the forced swimming test and tail suspension
      test, the inhibition of sucrose preference, and the decrease in the time spent in
      the center of open field. Furthermore, inhibition of the initial activation of
      hippocampal microglia by minocycline pretreatment also reversed the reduction in
      hippocampal microglial numbers as well as the behavioral abnormalities induced by
      CUS, CRS and CSDS treatment. These results provide compelling evidences to show
      that different types of chronic stresses can trigger the loss of endogenous
      hippocampal microglia and restoration of microglial numbers may have therapeutic
      values in major depression.

PMID- 28434166
TI  - Antibody Uptake Assay in the Embryonic Zebrafish Forebrain to Study Notch
      Signaling Dynamics in Neural Progenitor Cells In Vivo.
AB  - Stem cells can generate cell fate heterogeneity through asymmetric cell division
      (ACD). ACD derives from the asymmetric segregation of fate-determining molecules
      and/or organelles in the dividing cell. Radial glia in the embryonic zebrafish
      forebrain are an excellent model for studying the molecular mechanisms regulating
      ACD of stem cells in vertebrates, especially for live imaging concerning in vivo
      molecular and cellular dynamics. Due to the current difficulty in expressing
      fluorescent reporter-tagged proteins at physiological levels in zebrafish for
      live imaging, we have developed an antibody uptake assay to label proteins in
      live embryonic zebrafish forebrain with high specificity. DeltaD is a
      transmembrane ligand in Notch signaling pathway in the context of ACD of radial
      glia in zebrafish. By using this assay, we have successfully observed the in vivo
      dynamics of DeltaD for studying ACD of radial glia in the embryonic zebrafish
      forebrain.

PMID- 28434167
TI  - Analysis of S1P Receptor Expression by Uterine Immune Cells Using Standardized
      Multi-parametric Flow Cytometry.
AB  - Flow cytometry is a powerful tool for phenotypic and functional analyses of
      single immune cells. The increasing capability of flow cytometry technology has
      driven a more detailed understanding of immune cell subsets and functions in
      complex cellular systems such as the developing human decidua/placenta. We
      propose a standardized procedure for the isolation and analysis of human decidual
      natural killer (dNK) cells and this method can be extended to investigation of
      other uterine lymphocytes. Here this platform is used to examine the expression
      of sphingosine-1-phosphate (S1P) receptor and functional growth factors by dNK
      cells.

PMID- 28434165
TI  - Connexin Hemichannels in Astrocytes: An Assessment of Controversies Regarding
      Their Functional Characteristics.
AB  - Astrocytes in the mammalian central nervous system are interconnected by gap
      junctions made from connexins of the subtypes Cx30 and Cx43. These proteins may
      exist as hemichannels in the plasma membrane in the absence of a 'docked'
      counterpart on the neighboring cell. A variety of stimuli are reported to open
      the hemichannels and thereby create a permeation pathway through the plasma
      membrane. Cx30 and Cx43 have, in their hemichannel configuration, been proposed
      to act as ion channels and membrane pathways for different molecules, such as
      fluorescent dyes, ATP, prostaglandins, and glutamate. Published studies about
      astrocyte hemichannel behavior, however, have been highly variable and/or
      contradictory. The field of connexin hemichannel research has been complicated by
      great variability in the experimental preparations employed, a lack of highly
      specific pharmacological inhibitors and by confounding changes associated with
      genetically modified animal models. This review attempts to critically assess the
      gating, inhibition and permeability of astrocytic connexin hemichannels and
      proposes that connexins in their hemichannel configuration act as gated pores
      with isoform-specific permeant selectivity. We expect that some, or all, of the
      controversies discussed here will be resolved by future research and sincerely
      hope that this review serves to motivate such clarifying investigations.

PMID- 28434168
TI  - Dysphagia in a Patient with Cervical Dystonia.

PMID- 28434170
TI  - Establishment and characterization of novel epithelial-like cell lines derived
      from human periodontal ligament tissue in vitro.
AB  - In this study, novel human-derived epithelial-like cells (hEPLCs) lines were
      established from periodontal ligament (PDL) tissues, which were composed of a
      variety of cell types and exhibited complex cellular activities. To elucidate the
      putative features distinguishing these from epithelial rest of Malassez (ERM), we
      characterized hEPLCs based on cell lineage markers and tight junction protein
      expression. The aim of this study was, therefore, to establish and characterize
      hEPLCs lines from PDL tissues. The hEPLCs were isolated from PDL of third molar
      teeth. Cellular morphology and cell organelles were observed thoroughly. The
      characteristics of epithelial-endothelial-mesenchymal-like cells were compared in
      several markers by gene expression and immunofluorescence, to ERM and human
      umbilical-vein endothelial cells (HUVECs). The resistance between cellular
      junctions was assessed by transepithelial electron resistance, and inflammatory
      cytokines were detected by ELISA after infecting hEPLCs with periodontopathic
      bacteria. The hEPLCs developed into small epithelial-like cells in pavement
      appearance similar to ERM. However, gene expression patterns and
      immunofluorescence results were different from ERM and HUVECs, especially in
      tight junction markers (Claudin, ZO-1, and Occludins), and endothelial markers
      (vWF, CD34). The transepithelial electron resistance indicated higher resistance
      in hEPLCs, as compared to ERM. Periodontopathic bacteria were phagocytosed with
      upregulation of inflammatory cytokine secretion within 24 h. In conclusion,
      hEPLCs that were derived using the single cell isolation method formed tight
      multilayers colonies, as well as strongly expressed tight junction markers in
      gene expression and immunofluorescence. Novel hEPLCs lines exhibited differently
      from ERM, which might provide some specific functions such as metabolic exchange
      and defense mechanism against bacterial invasion in periodontal tissue.

PMID- 28434169
TI  - Inflammation, Immune Activation, and Antiretroviral Therapy in HIV.
AB  - PURPOSE OF REVIEW: This review focuses on the differential effects of
      contemporary antiretrovirals on systemic inflammation as heightened immune
      activation is linked to important co-morbidities and mortality with HIV
      infection. RECENT FINDINGS: Antiretroviral therapy (ART) reduces dramatically
      systemic inflammation and immune activation, but not to levels synchronous with
      HIV-uninfected populations. In one ART initiation trial, integrase inhibitors
      appear to reduce inflammation to a greater degree than non-nucleoside reverse
      transcriptase inhibitors (NNRTIs); however, it is not clear that there are
      beneficial effects on inflammation resulting from treatment with integrase
      inhibitors compared to PIs, between PIs and NNRTIs, between specific nucleoside
      reverse transcriptase inhibitors, or with maraviroc in ART-naive patients. In ART
      switch studies, changing to an integrase inhibitor from a PI-, NNRTI-, or
      enfuvirtide-containing regimen has resulted in improvement in several markers of
      inflammation. Additional research is needed to conclusively state whether there
      are clear differences in effects of specific antiretrovirals on inflammation and
      immune activation in HIV.

PMID- 28434171
TI  - Peroxidatic cysteine residue of peroxiredoxin 2 separated from human red blood
      cells treated by tert-butyl hydroperoxide is hyperoxidized into sulfinic and
      sulfonic acids.
AB  - Peroxiredoxin 2 (Prx2) is a redox enzyme that is abundantly expressed in red
      blood cells (RBCs) and has been the focus of clinical attention for monitoring
      the oxidative status. We previously developed a method to quantify the reduced
      and hyperoxidized forms of Prx2 in human RBCs using reverse-phase high
      performance liquid chromatography (HPLC). In the present study, we investigated
      the hyperoxidative status of Prx2 at the molecular level in a post-translational
      modification analysis using a liquid chromatography-tandem mass spectrometry (LC
      MS/MS) system. The LC-MS/MS analysis of the trypsin digests of Prx2 fractionated
      by reverse-phase HPLC demonstrated that the cysteine-51 residue (Cys-51) of the
      protein was modified with the hyperoxidative functional groups, sulfinic acid (
      SO2H) and sulfonic acid (-SO3H), in RBCs treated with tert-butyl hydroperoxide (t
      BHP). Furthermore, a selected ion monitoring (SIM) analysis quantitatively showed
      that sulfinic acid- and sulfonic acid-induced modifications in Prx2 Cys-51 were
      increased by the treatment with the oxidant. It was demonstrated that the
      peroxidatic cysteine of Prx2 separated using our HPLC system for oxidative
      monitoring was hyperoxidized into sulfinic acid and sulfonic acid in RBCs under
      an oxidative stress condition.

PMID- 28434172
TI  - Lactobacillus paracasei strain 06TCa19 suppresses inflammatory chemokine induced
      by Helicobacter pylori in human gastric epithelial cells.
AB  - Helicobacter (H.) pylori infection is an important risk factor for gastric cancer
      that causes gastric inflammation. Inflammatory chemokines such as interleukin
      (IL)-8 and regulated on activation normal T cell expressed and secreted (RANTES)
      are elevated in the gastric mucosa by H. pylori. This study aimed to investigate
      the effects of Lactobacillus paracasei strain 06TCa19, a probiotic strain, on IL
      8 and RANTES expression and production induced by H. pylori using human gastric
      epithelial cell lines. Strain 06TCa19 was shown to suppress H. pylori-mediated
      elevation of gene expression related to these chemokines in MKN45 cells. The
      strain also suppressed the increase in IL-8 and RANTES products induced by H.
      pylori in AGS cells as well as in MKN45 cells. In MKN45 cells inoculated with H.
      pylori, strain 06TCa19 was shown to downregulate the activation of NF-kappaB and
      p38 MAPK signaling pathways. Additionally, the level of the CagA virulence
      protein of H. pylori in the MKN45 cells and the number of viable H. pylori
      adhering to MKN45 cells decreased with the addition of strain 06TCa19. Moreover,
      the strain 06TCa19 notably increased lactic acid in the supernatant of MKN45
      cells. Thus, lactic acid released from strain 06TCa19 might have inhibited the
      adhesion of H. pylori to MKN45 cells and prevented the insertion of H. pylori
      CagA into the cells, and elevation of IL-8 and RANTES genes and proteins might be
      suppressed by downregulating the NF-kappaB and p38 MAPK pathways. Therefore, use
      of strain 06TCa19 may prevent H. pylori-associated gastric inflammation.

PMID- 28434173
TI  - The effect of resilience on task persistence and performance during repeated
      exposure to heat pain.
AB  - The Pain Resilience Scale was recently developed to assess dimensions of
      resilience critical to pain-related adaptation and was found to predict
      experimental pain sensitivity in a pain-free population. Pain resilience has also
      been theoretically linked to behavioral persistence despite pain. To date,
      however, this hypothesis has not been experimentally tested. To address this gap
      in the literature, in the current study 105 healthy young adults underwent a
      baseline administration of the Paced Auditory Serial Addition Test (PASAT), a
      stressful mental arithmetic task, delivered with somatosensory distraction (i.e.
      detection of warm and cool thresholds), and finally simultaneous administration
      of the PASAT and a series of five heat pain threshold assessments. Results of
      hierarchical multiple linear regressions indicated that, after controlling for
      scores on a baseline PASAT and pain sensitivity, pain resilience was positively
      related to task persistence, B = 0.12, p = 0.04, and task performance, B = 0.14,
      p = 0.04, on the PASAT. These findings provide novel support for the relationship
      between pain resilience and behavioral perseverance.

PMID- 28434174
TI  - Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non
      Small-Cell Lung Carcinoma.
AB  - Large tumor suppressor (LATS) is an important member of the Hippo pathway which
      can regulate organ size and cell proliferation. However, very little is known
      about the expression and clinical significance of LATS in lung cancer especially
      from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter
      hypermethylation (by methylation-specific PCR) and expression (by real-time PCR)
      in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their
      corresponding normal lung tissue samples. We found promoter hypermethylation
      frequencies of LATS1 & LATS1to be 66.66% (46/69) and 71% (49/69) in NSCLC
      tissues. Decreased LATS1 & LATS2 mRNA expression was found in 55% and 66.66% of
      NSCLC patients. The LATS1 mRNA expression was significantly higher in normal lung
      tissues. Also, the mRNA levels of LATS1 and LATS2 NSCLC tissues with
      hypermethylation were significantly lower. Multivariable analysis confirmed that
      LATS1 under expression increased the hazard of death after adjusting for other
      clinicopathological factors. Importantly, the loss of LATS1 mRNA expression was
      associated with overall short survival. LATS1 is an independent prognostic factor
      and may play an important role in NSCLC progression and may serve as a novel
      therapeutic target of NSCLC.

PMID- 28434175
TI  - Myoxinol ointment for the treatment of acute fissure.
AB  - Myoxinol is a complex of oligopeptides obtained from the seeds of Hibiscus
      esculentus used in cosmetic as natural alternative to botulin toxin. The aim of
      the study was to evaluate the safety and effectiveness of local myoxinol for the
      treatment of acute anal fissure. All the consecutive patients with acute fissure
      treated from January to June 2014 underwent 30 days of topical treatment
      (twice/day) with a mioxinol based ointment. Pain, symptomatic relief, fissure
      healing and re-epithelization, 1-year recurrence rate, subjective satisfaction
      and need for further treatments were evaluated. During the study period 157
      patients were eligible for data analysis (91 males: 58%; mean age 38 years: range
      17-83). Median anal pain score was 7.1 pre-treatment and 1.7 and 0.9 after 30
      days and 12 months from treatment, respectively (p: 0.0001). After the treatment
      period complete healing was achieved in 103 patients (65.5%), relevant
      improvement in 31 (20%) and no improvement in 21 patients (13.5%). Overall
      efficacy rate was 85.5%. A significant difference was reported considering
      patients with pre-treatment VAS between 1-5 and 6-10 (p: 0.004). Twenty-nine
      patients (18.5%) required further treatments. Hydrolyzed Hibiscus esculentus
      extract was proven to be an effective and well-tolerated topical treatment for
      acute fissure, with a high healing rate, a significant reduction of pain and a
      low 1-year recurrence rate.

PMID- 28434176
TI  - Persistent and recurrent hyperparathyroidism.
AB  - Despite remarkable progress in imaging modalities and surgical management,
      persistence or recurrence of primary hyperparathyroidism (PHPT) still occurs in
      2.5-5% of cases of PHPT. The aim of this review is to expose the management of
      persistent and recurrent hyperparathyroidism. A literature search was performed
      on MEDLINE using the search terms "recurrent" or "persistent" and
      "hyperparathyroidism" within the past 10 years. We also searched the reference
      lists of articles identified by this search strategy and selected those we judged
      relevant. Before considering reoperation, the surgeon must confirm the diagnosis
      of PHPT. Then, the patient must be evaluated with new imaging modalities. A
      single adenoma is found in 68% of cases, multiglandular disease in 28%, and
      parathyroid carcinoma in 3%. Others causes (<1%) include parathyromatosis and
      graft recurrence. The surgeon must balance the benefits against the risks of a
      reoperation (permanent hypocalcemia and recurrent laryngeal nerve palsy). If
      surgery is necessary, a focused approach can be considered in cases of
      significant imaging foci, but in the case of multiglandular disease, a bilateral
      neck exploration could be necessary. Patients with multiple endocrine neoplasia
      syndromes are at high risk of recurrence and should be managed regarding their
      hereditary pathology. The cure rate of persistent-PHPT or recurrent-PHPT in
      expert centers is estimated from 93 to 97%. After confirming the diagnosis of
      PHPT, patients with persistent-PHPT and recurrent-PHPT should be managed in an
      expert center with all dedicated competencies.

PMID- 28434177
TI  - Eating disorders and food addiction in men with heroin use disorder: a controlled
      study.
AB  - PURPOSE: We aimed to determine the prevalence estimates of binge eating disorder,
      bulimia nervosa, anorexia nervosa, and food addiction in men with heroin use
      disorder and a matched sample of control participants. METHODS: A group of 100
      men with heroin use disorder, consecutively admitted to a detoxification and
      therapy unit, were screened for DSM-5 eating disorders, along with a group of 100
      male controls of similar age, education, and body mass index. The Yale Food
      Addiction Scale (YFAS), the Barratt Impulsivity Scale-version 11, and the Eating
      Attitudes Test were used for data collection. Patients were also evaluated for
      various aspects of heroin use disorder (e.g., craving) using the Addiction
      Profile Index. RESULTS: Binge eating disorder that met DSM-5 criteria was more
      prevalent in patients with heroin use disorder (21%) than in control subjects
      (8%) (odds ratio 3.1, 95% confidence interval 1.3-7.3; p < 0.01). Food addiction
      based on the YFAS was also more common among men with heroin use disorder (28%)
      than among control participants (12%) (odds ratio 2.9, 95% confidence interval
      1.4-6.1; p < 0.01). A current food addiction was associated with more severe
      craving and having a history of suicide attempts in the patients. CONCLUSIONS: Co
      occurring binge eating disorder and food addiction are highly frequent in men
      with heroin use disorder. Screening for binge eating disorder and food addiction
      in patients with substance use disorder is important, as interventions may
      improve treatment outcome in this patient group.

PMID- 28434178
TI  - Massilia chloroacetimidivorans sp. nov., a chloroacetamide herbicide-degrading
      bacterium isolated from soil.
AB  - A Gram-stain negative, rod-shaped, aerobic bacterial strain, designated TA-C7eT,
      was isolated from an agricultural soil obtained from Taean region, Korea.
      Phylogenetically, the strain was grouped with the genus Massilia and shared 95.33
      97.97% 16S rRNA sequence similarity with the type strains of other species of the
      genus Massilia. The DNA-DNA hybridisation between TA-C7eT and Massilia
      haematophila KACC 13771T, Massilia suwonesis KACC 12635T, and Massilia
      yuzhufengensis KACC 16569T revealed a low level of relatedness (<40%). The low
      levels of DNA-DNA hybridisation values identified strain TA-C7eT as a novel
      species in the genus Massilia. The major fatty acids of the strain were C16:0
      (37.3%) and summed feature 3 (C16:1 omega7c and/or C16:1 omega6c) (40.6%). Q-8
      was identified as the only isoprenoid quinone. The polar lipids profile of the
      strain showed the presence of phosphatidylglycerol, phosphatidylethanolamine,
      diphosphatidylglycerol, an unidentified aminophospholipid and three unidentified
      lipids. The DNA G+C content of the strain was found to be 63.2 mol%. On the basis
      of the phenotypic, genotypic and chemotaxonomic characteristics, strain TA-C7eT
      represents a novel species in the genus Massilia, for which the name Massilia
      chloroacetimidivorans sp. nov. (=KACC 18674T = NBRC 112463T) is proposed.

PMID- 28434179
TI  - Erratum.

PMID- 28434180
TI  - Stated Uptake of Physical Activity Rewards Programmes Among Active and
      Insufficiently Active Full-Time Employees.
AB  - BACKGROUND: Employers are increasingly relying on rewards programmes in an effort
      to promote greater levels of activity among employees; however, if enrolment in
      these programmes is dominated by active employees, then they are unlikely to be a
      good use of resources. OBJECTIVE: This study uses a stated-preference survey to
      better understand who participates in rewards-based physical activity programmes,
      and to quantify stated uptake by active and insufficiently active employees.
      METHODS: The survey was fielded to a national sample of 950 full-time employees
      in Singapore between 2012 and 2013. Participants were asked to choose between
      hypothetical rewards programmes that varied along key dimensions and whether or
      not they would join their preferred programme if given the opportunity. A mixed
      logit model was used to analyse the data and estimate predicted uptake for
      specific programmes. We then simulated employer payments based on predictions for
      the percentage of each type of employee likely to meet the activity goal.
      RESULTS: Stated uptake ranged from 31 to 67% of employees, depending on programme
      features. For each programme, approximately two-thirds of those likely to enrol
      were insufficiently active. CONCLUSION: Results showed that insufficiently active
      employees, who represent the majority, are attracted to rewards-based physical
      activity programmes, and at approximately the same rate as active employees, even
      when enrolment fees are required. This suggests that a programme with generous
      rewards and a modest enrolment fee may have strong employee support and be within
      the range of what employers may be willing to spend.

PMID- 28434181
TI  - Management Options for Biochemically Recurrent Prostate Cancer.
AB  - Prostate cancer is the most common solid tumor malignancy in men worldwide.
      Treatment with surgery and radiation can be curative in organ-confined disease.
      Unfortunately, about one third of men develop biochemically recurrent disease
      based only on rising prostate-specific antigen (PSA) in the absence of visible
      disease on conventional imaging. For these patients with biochemical recurrent
      prostate cancer, there is no uniform guideline for subsequent management. Based
      on available data, it seems prudent that biochemical recurrent prostate cancer
      should initially be evaluated for salvage radiation or prostatectomy, with
      curative intent. In selected cases, high-intensity focused ultrasound and
      cryotherapy may be considered in patients that meet very narrow criteria as
      defined by non-randomized trials. If salvage options are not practical or
      unsuccessful, androgen deprivation therapy (ADT) is a standard option for disease
      control. While some patients prefer ADT to manage the disease immediately, others
      defer treatment because of the associated toxicity. In the absence of definitive
      randomized data, patients may be followed using PSA doubling time as a trigger to
      initiate ADT. Based on retrospective data, a PSA doubling time of less than 3-6
      months has been associated with near-term development of metastasis and thus
      could be used signal to initiate ADT. Once treatment is begun, patients and their
      providers can choose between an intermittent and continuous ADT strategy. The
      intermittent approach may limit side effects but in patients with metastatic
      disease studies could not exclude a 20% greater risk of death. In men with
      biochemical recurrence, large studies have shown that intermittent therapy is non
      inferior to continuous therapy, thus making this a reasonable option. Since
      biochemically recurrent prostate cancer is defined by technological limitations
      of radiographic detection, as new imaging (i.e., PSMA) strategies are developed,
      it may alter how the disease is monitored and perhaps managed. Furthermore,
      patients have no symptoms related to their disease and thus many prefer options
      that minimize toxicity. For this reason, herbal agents and immunotherapy are
      under investigation as potential alternatives to ADT and its accompanying side
      effects. New therapeutic options combined with improved imaging to evaluate the
      disease may markedly change how biochemically recurrent prostate cancer is
      managed in the future.

PMID- 28434182
TI  - Recent Trends in Alcohol and Other Drug Use Among Police Detainees in New
      Zealand, 2010-2015.
AB  - BACKGROUND: New Zealand has unusual patterns of recreational substance use by
      international standards including low levels of cocaine and heroin use, and high
      methamphetamine use. AIMS: This paper examines recent trends in alcohol and other
      drug use among police detainees in New Zealand over the past six years. METHOD:
      The paper utilises data from the New Zealand Arrestee Drug Use Monitoring (NZ
      ADUM) study. NZ-ADUM interviewed approximately 800 police detainees each year at
      four central city police watch houses (i.e. Whangarei, Auckland, Wellington,
      Christchurch) from 2010 to 2015. RESULTS: The proportion of police detainees who
      had used methamphetamine in the previous year increased from 28% in 2012 to 36%
      in 2015. Drinking prior to arrest declined from 41% in 2013 to 28% in 2015. The
      use of cannabis in the past year declined slightly from 76% in 2011 to 69% in
      2015. The proportion using ecstasy in the previous year steadily declined from
      28% in 2011 to 19% in 2015. Only small minorities had recently used cocaine or an
      opioid. Use of methamphetamine and ecstasy increased in Christchurch. CONCLUSION:
      Growing methamphetamine use is consistent with record seizures of methamphetamine
      over the past 2-3 years. Increasing drug use in Christchurch may reflect factors
      related to the devastating earthquakes in 2011 and the subsequent city rebuild,
      including an influx of construction workers, more organised trafficking groups
      and earthquake-related stress. The decline in cannabis use may be related to the
      emergence of 'legal' synthetic cannabinoids. The decline in ecstasy use may be
      the result of recent domestic enforcement operations and the overall global
      shortage of MDMA. The decline in alcohol drinking may be due to the introduction
      of pre-charge formal warnings for minor alcohol and disorder offences, and new
      restrictions on alcohol premise opening hours. Acknowledgements: The New Zealand
      Drug Use Monitoring (NZ-ADUM) research study is funded by the New Zealand Police
      and is conducted by SHORE and Whariki Research Centre, College of Health at
      Massey University, Auckland. We would like to thank New Zealand Police staff at
      Whangarei, Auckland Central, Wellington Central and Christchurch Central police
      watch houses for their assistance and cooperation with this research. We would
      also like to thank all the interviewers who worked with us on NZ-ADUM and all the
      police detainees who agreed to be interviewed for the study. The views expressed
      in this paper are entirely our own and do not necessarily reflect those of New
      Zealand Police.

PMID- 28434183
TI  - Impacts of forestry on boreal forests: An ecosystem services perspective.
AB  - Forests are widely recognized as major providers of ecosystem services, including
      timber, other forest products, recreation, regulation of water, soil and air
      quality, and climate change mitigation. Extensive tracts of boreal forests are
      actively managed for timber production, but actions aimed at increasing timber
      yields also affect other forest functions and services. Here, we present an
      overview of the environmental impacts of forest management from the perspective
      of ecosystem services. We show how prevailing forestry practices may have
      substantial but diverse effects on the various ecosystem services provided by
      boreal forests. Several aspects of these processes remain poorly known and
      warrant a greater role in future studies, including the role of community
      structure. Conflicts among different interests related to boreal forests are most
      likely to occur, but the concept of ecosystem services may provide a useful
      framework for identifying and resolving these conflicts.

PMID- 28434184
TI  - Complex problems and unchallenged solutions: Bringing ecosystem governance to the
      forefront of the UN sustainable development goals.
AB  - Sustainable development aims at addressing economic, social, and environmental
      concerns, but the current lack of responsive environmental governance hinders
      progress. Short-term economic development has led to limited actions,
      unsustainable resource management, and degraded ecosystems. The UN Sustainable
      Development Goals (SDGs) may continue to fall short of achieving significant
      progress without a better understanding of how ecosystems contribute to achieving
      sustainability for all people. Ecosystem governance is an approach that
      integrates the social and ecological components for improved sustainability and
      includes principles such as adaptive ecosystem co-management, subsidiarity, and
      telecoupling framework, as well as principles of democracy and accountability. We
      explain the importance of ecosystem governance in achieving the SDGs, and suggest
      some ways to ensure that ecosystem services are meaningfully considered. This
      paper reflects on how integration of these approaches into policies can enhance
      the current agenda of sustainability.

PMID- 28434185
TI  - Can targeted policies reduce obesity and improve obesity-related behaviours in
      socioeconomically disadvantaged populations? A systematic review.
AB  - This review synthesized evidence from controlled studies pertaining to the impact
      of targeted policies on anthropometric, dietary and physical activity outcomes
      amongst socioeconomically disadvantaged children and adults. Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses-Equity guidelines were followed.
      Eligible studies were published from 2004 to August 2015 and examined the impact
      of targeted policies on anthropometric, dietary and physical activity outcomes
      amongst socioeconomically disadvantaged populations. Twenty articles (18 studies)
      were included. Eight studies examined organizational policies within multi
      component interventions in schools. Common elements of successful policy
      containing interventions included nutritional standards, enhancements to physical
      education, additional physical activity opportunities, school self-assessments,
      and nutrition and physical activity education. Of the 10 studies of government
      policies, policies providing information/education and fruit and vegetable
      subsidies had positive impacts amongst children, but no impact amongst adults.
      Policies involving changes to built environments yielded nearly uniformly null
      findings in children and adults. Overall, the largest quantity of high-quality
      evidence of effectiveness was for comprehensive interventions that included
      school policies, and government policies targeting disadvantaged children in
      schools. None of the government policies targeting disadvantaged adults proved
      effective. Interventions during childhood may ameliorate negative obesity-related
      manifestations of socioeconomic disadvantage. Gaps in knowledge remain
      surrounding effective policies in adults, adolescents and very young children.

PMID- 28434187
TI  - Ultrasound-Guided Intra-articular Injection of the Radio-ulnar and Radio-humeral
      Joints and Ultrasound-Guided Dry Needling of the Affected Limb Muscles to Relieve
      Fixed Pronation Deformity and Myofascial Issues around the Shoulder, in a Case of
      Complex Regional Pain Syndrome Type 1.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) occurs due to different
      pathophysiological mechanisms. Presently there is no description of definitive
      treatment that can resolve the especially recalcitrant motor issues of disability
      in CRPS type 1 (CRPS-1). CASE REPORT: We have herein described the successful
      management of motor disability with a multimodal approach in a patient with CRPS
      1 that occurred as a result of a fracture sustained in the lower end of the
      radius. Sensory/sudomotor/vasomotor symptoms were relieved completely by
      medications and stellate ganglion block in 2 weeks. Ultrasound-guided dry
      needling secured near-complete improvement of shoulder and hand movements in 45
      days. Ultrasound guided intra-articular (radio-ulnar and radio-humeral joint)
      injections with steroid reduced residual pain and improved forearm movements by
      50% initially. The patient continued to receive regular sessions of dry needling,
      physiotherapy, and cognitive behavioral therapy. By the end of 1 year, the
      functions of the limb improved remarkably, as did the functional outcome scores.
      CONCLUSION: In this patient with CRPS-1, intra-articular injections with steroid
      reduced nociception in the affected local structures and sensitization in the
      nervous system; dry needling resolved the myofascial issues; sustained
      physiotherapy maintained the motor recovery; and behavioral therapy techniques
      addressed the cognitive and life stress issues. It was concluded that the
      presenting symptoms in this case were a consequence of interactions between
      humoral, nervous, and myofascial systems.

PMID- 28434186
TI  - New thiourea and 1,3-thiazolidin-4-one derivatives effective on the HIV-1 virus.
AB  - Thiourea derivatives have been reported to possess many biological activities,
      among them antiviral and antitumoral properties. As part of our continuing effort
      to develop new active compounds, we report the synthesis and the evaluation of
      new fifteen thiourea derivatives with 1,3-benzothiazole-2-yl moiety, among them a
      group of biologically active (1-7) also underwent cyclization to 1,3-thiazolidin
      4-ones. Molecular structure of four compounds (4, 13, 15 and 3a) was determined
      by an X-ray crystallography. We here report the evaluation of their cytotoxicity
      against human leukaemia/lymphoma- and solid tumour-derived cell lines and of
      their antiviral activity against HIV-1 and representatives of ssRNA and dsDNA
      viruses. Derivative 5 showed an interesting activity against HIV-1 wild type and
      against variants carrying clinically relevant mutations. A colorimetric enzyme
      immunoassay clarified its mode of action as a non-nucleoside inhibitor of the
      reverse transcriptase.

PMID- 28434188
TI  - Drivers of community assembly in tropical forest restoration sites: role of local
      environment, landscape, and space.
AB  - There is increasing recognition that community assembly theory can offer valuable
      insights for ecological restoration. We studied community assembly processes
      following tropical forest restoration efforts, using dung beetles (Scarabaeinae)
      as a focal taxon to investigate taxonomic and functional patterns of biodiversity
      recovery. We evaluated the relative importance of the local environment (i.e.,
      canopy cover, understory cover, tree basal area, and soil texture), landscape
      context (i.e., habitat patch proximity and availability and percentage of
      surrounding area classified as natural forest or Eucalyptus spp. plantation), and
      space (i.e., spatial proximity of the study areas to estimate dispersal
      limitation or unmeasured spatially structured processes) on dung beetle species
      and functional trait composition across a gradient of 15 restoration sites in
      Brazilian Atlantic Forest. We also assessed which factors were the primary
      determinants in the establishment of individual dung beetle functional groups,
      classified according to size, food relocation habit, diet, and period of flight
      activity. Both species and functional trait composition were most strongly
      influenced by the local environment, indicating that assembly was predominantly
      driven by niche-based processes. Most of the variation explained by space was co
      explained by local environment and landscape context, ruling out a strong
      influence of dispersal limitation and random colonization on assembly following
      restoration. In addition, nearly all of the variance explained by landscape
      context was co-explained by local environment, suggesting that arrival and
      establishment at a site depends on both local and landscape-scale environmental
      factors. Despite strong evidence for niche-based assembly, a large amount of
      variation remained unexplained in all models, suggesting that stochastic
      processes and/or unmeasured environmental variables also play an important role.
      The relative importance of local environment, landscape context, and space
      changed considerably when analyzing the assembly mechanisms of each functional
      group separately. Therefore, to recover distinct functional traits in restoration
      sites, it may be necessary to manipulate different components of the local
      environment and surrounding landscape. Overall, this study shows that assembly
      rules can help to better understand recovery processes, enabling improvement of
      future restoration efforts.

PMID- 28434189
TI  - Changes in rumen protozoal community by condensed tannin fractions of different
      molecular weights from a Leucaena leucocephala hybrid in vitro.
AB  - AIMS: To evaluate the effects of condensed tannins (CTs) fractions of differing
      molecular weights (MWs) from a Leucaena leucocephala hybrid-Rendang on the rumen
      protozoal community in vitro. METHODS AND RESULTS: The effects of unfractionated
      CTs (F0) and CT fractions of different MWs (F1 > F2 > F3 > F4 > F5) on protozoal
      population and community were evaluated in vitro using rumen microbes and ground
      guinea grass as the substrate. Higher-MW CT fractions F1 and F2 significantly (P
      < 0.05) decrease the number of ciliate protozoa. The real-time PCR analysis
      showed that the total protozoa was significantly (P < 0.05) lower in F0 and all
      CTs with fractions F1 and F2 having the lowest value. High-throughput sequencing
      of the partial 18S rRNA gene showed that the genus Entodinium significantly (P <
      0.05) decreased with increasing MWs of CT, whereas Anoplodinium-Diplodinium were
      significantly (P < 0.05) increased. Inclusion of the highest MW CT fraction F1
      decreased the relative abundance of the minor genera such as Eudiplodinium and
      Polyplastron compared to the control and CT fractions F2-F5. CONCLUSION: CTs of
      differing MWs could reduce and alter the rumen protozoa population in vitro. This
      effect was more pronounced for higher-MW CTs. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The high MW CTs should be considered as a feed supplement in the ruminant
      diet to reduce the protozoal population which are known to be associated with
      methanogens as a means to mitigate methane production in the rumen.

PMID- 28434190
TI  - Mixed-severity fire history at a forest-grassland ecotone in west central British
      Columbia, Canada.
AB  - This study examines spatially variable stand structure and fire-climate
      relationships at a low elevation forest-grassland ecotone in west central British
      Columbia, Canada. Fire history reconstructions were based on samples from 92 fire
      scarred trees and stand demography from 27 plots collected over an area of about
      7 km2 . We documented historical chronologies of widespread fires and localized
      grassland fires between AD 1600 and 1900. Relationships between fire events,
      reconstructed values of the Palmer Drought Severity Index, and annual
      precipitation were examined using superposed epoch and bivariate event analyses.
      Widespread fires occurred during warm, dry years and were preceded by multiple
      anomalously dry, warm years. Localized fires that affected only grassland
      proximal forests were more frequent than widespread fires. These localized fires
      showed a lagged, positive relationship with wetter conditions. The landscape
      pattern of forest structure provided further evidence of complex fire activity
      with multiple plots shown to have experienced low-, mixed-, and/or high-severity
      fires over the last four centuries. We concluded that this forest-grassland
      ecotone was characterized by fires of mixed severity, dominated by frequent, low
      severity fires punctuated by widespread fires of moderate to high severity. This
      landscape-level variability in fire-climate relationships and patterns in forest
      structure has important implications for fire and grassland management in west
      central British Columbia and similar environments elsewhere. Forest restoration
      techniques such as prescribed fire and thinning are oftentimes applied at the
      forest-grassland ecotone on the basis that historically high frequency, low
      severity fires defined the character of past fire activity. This study provides
      forest managers and policy makers with important information on mixed-severity
      fire activity at a low elevation forest-grassland ecotone, a crucial prerequisite
      for the effective management of these complex ecosystems.

PMID- 28434192
TI  - Modified Ipswich procedure: Patient-perceived benefit and surgical outcomes in a
      series of ten patients.

PMID- 28434193
TI  - Mediators of socioeconomic differences in adiposity among youth: a systematic
      review.
AB  - BACKGROUND: Youth with a low socioeconomic position in developed countries are at
      a disproportionately higher risk of being overweight or obese than their
      counterparts. Tackling these inequalities requires that the mechanisms behind
      them are well understood. OBJECTIVES: The aim of this review was to summarize
      existing evidence regarding the factors that mediate or contribute to the
      explanation of the relationship between socioeconomic position and adiposity
      among youth. METHODS AND RESULTS: A systematic literature search, conducted using
      the databases Medline, Embase, Web of Science and PsycINFO, yielded 28 eligible
      studies. These studies were of low to moderate methodological quality. The most
      consistent mediators of the association between socioeconomic position and
      adiposity identified in this review were as follows: consumption of sugar
      sweetened beverages, television viewing, computer use, parental body mass index,
      breastfeeding duration, breakfast consumption, maternal smoking during pregnancy
      and infant feeding practices. The mediating role of physical activity as well as
      fruit and vegetable consumption was found to be indeterminate. Other potential
      mediators were explored in too few studies to make conclusions about their
      mediating role. CONCLUSION: The review found several modifiable factors that
      could be targeted as feasible in interventions aimed at reducing socioeconomic
      differences in overweight and obesity among youth.

PMID- 28434191
TI  - The effect of parotid gland-sparing intensity-modulated radiotherapy on salivary
      composition, flow rate and xerostomia measures.
AB  - OBJECTIVES: To describe parotid gland (PG) saliva organic and inorganic
      composition and flow rate changes, after curative intensity-modulated
      radiotherapy (IMRT) for head and neck cancer (HNC), and analyse the relationship
      between PG saliva analytes and xerostomia measures. METHODS AND MATERIALS: Twenty
      six patients recruited to five prospective phase 2 or 3 trials which assessed
      toxicity and efficacy of IMRT by HNC subsite, provided longitudinal PG saliva.
      Salivary flow rate, and subjective and objective xerostomia measures were
      prospectively collected and saliva tested for inorganic and organic analytes.
      Statistical comparisons of longitudinal analyte changes and analysis for a
      relationship between dichotomized xerostomia score and saliva analytes were
      performed. RESULTS: One hundred and forty-two PG saliva samples from 26 patients
      were analysed. At 3-6 months after IMRT, stimulated and unstimulated saliva
      showed significantly decreased flow rate, total protein (TP) secretion rate,
      phosphate concentration and increased lactoferrin (LF) concentration. Stimulated
      saliva alone had elevated LF secretion rate and beta-2-microglobulin (B2 M)
      concentration with decreased calcium (Ca2+ ) and magnesium (Mg2+ ) concentrations
      and Ca2+ secretion rate. At >12 months, under stimulated and unstimulated
      conditions, increased LF concentration and decreased Mg2+ and phosphate
      concentration persisted and, in stimulated saliva, there was decreased potassium
      (K+ ) and Mg2+ concentration. Unstimulated TP secretion rate was lower in the
      presence of high-grade xerostomia. Otherwise, no relationship between xerostomia
      grade and PG salivary flow rate, TP and Ca2+ secretion rate was found.
      CONCLUSION: Fewer significant differences in PG saliva analytes >12 months after
      IMRT indicate good functional recovery. Residual xerostomia after IMRT will only
      be further reduced by addressing the sparing of subsites of the PG or other
      salivary gland tissues, in addition to the PG.

PMID- 28434194
TI  - Cytotoxic Triterpenoids from the Stalks of Microtropis triflora.
AB  - Bioassay-guided phytochemical investigation of the stalks of Microtropis triflora
      Merr. & F.L. Freeman led to the isolation of ten triterpenes 1 - 10, including
      one novel compound 3,24-epoxy-2alpha,24-dihydroxyfriedelan-29-oic acid (1). Their
      chemical structures were identified on the basis of spectroscopic analysis,
      including HR-ESI mass spectrometry, 1D- and 2D-NMR (1 H, 13 C, 1 H,1 H-COSY,
      HSQC, HMBC, and NOESY), and by comparison with the data reported. The
      cytotoxicities of compounds 1 - 10 against a panel of cultured human tumor cell
      lines (Bcap37, SMMC7721, HeLa, CNE) were evaluated. The new compound 1 showed
      moderate anti-tumor activities with IC50 values of 39.22, 29.24, 23.28, and 68.81
      MUm/ml, respectively. These results might be helpful for explaining the use of M.
      triflora in traditional medicine. Triterpenes are characteristic of Microtropis
      genus and could be useful as potential chemotaxonomic markers.

PMID- 28434195
TI  - Use of isavuconazole in a patient with voriconazole-induced QTc prolongation.
AB  - A 22-year-old woman with cystic fibrosis developed QTc interval prolongation
      following lung transplantation in the setting of voriconazole therapy. After the
      discontinuation of voriconazole and initiation of isavuconazole, her QTc interval
      normalized. This case highlights the unique property of QTc interval shortening
      by isavuconazole among the triazole antifungals.

PMID- 28434197
TI  - Multimodal signalling in estrildid finches: song, dance and colour are associated
      with different ecological and life-history traits.
AB  - Sexual traits (e.g. visual ornaments, acoustic signals, courtship behaviour) are
      often displayed together as multimodal signals. Some hypotheses predict joint
      evolution of different sexual signals (e.g. to increase the efficiency of
      communication) or that different signals trade off with each other (e.g. due to
      limited resources). Alternatively, multiple signals may evolve independently for
      different functions, or to communicate different information (multiple message
      hypothesis). We evaluated these hypotheses with a comparative study in the family
      Estrildidae, one of the largest songbird radiations, and one that includes many
      model species for research in sexual selection and communication. We found little
      evidence for either joint evolution or trade-offs between song and colour
      ornamentation. Some negative correlations between dance repertoire and song
      traits may suggest a functional compromise, but generally courtship dance also
      evolved independently from other signals. Instead of correlated evolution, we
      found that song, dance and colour are each related to different socio-ecological
      traits. Song complexity evolved together with ecological generalism, song
      performance with investment in reproduction, dance with commonness and habitat
      type, whereas colour ornamentation was shown previously to correlate mostly with
      gregariousness. We conclude that multimodal signals evolve in response to various
      socio-ecological traits, suggesting the accumulation of distinct signalling
      functions.

PMID- 28434196
TI  - Role of gut microbiota, bile acids and their cross-talk in the effects of
      bariatric surgery on obesity and type 2 diabetes.
AB  - Type 2 diabetes mellitus is becoming increasingly prevalent worldwide, and has
      become one of the greatest threats to global health. Bariatric surgery was
      initially designed to achieve weight loss, and subsequently was noted to induce
      improvements or remission of type 2 diabetes. Currently, these bariatric
      operations, such as Roux-en-Y gastric bypass and sleeve gastrectomy, are the most
      effective procedures for the treatment of obesity and type 2 diabetes mellitus
      worldwide. However, the specific mechanism mediating the beneficial effects of
      metabolic surgery has remained largely unknown. Those mechanical explanations,
      such as restriction and malabsorption, are challenged by accumulating evidence
      from human and animal models of these procedures, which points to the weight
      independent factors, such as hormones, bile acids, gut microbiota, nervous system
      and other potential underlying mechanisms. A growing body of evidence suggests
      that gut microbiota are associated with the development of several metabolic
      disorders, and bile acids and FXR signaling are important for the metabolic
      benefits of bariatric surgery. Given the close relationship between bacteria and
      bile acids, it is reasonable to propose that microbiota-bile acid interactions
      play a role in the mechanisms underlying the effects of metabolic surgery.

PMID- 28434198
TI  - Eukaryotic diversity in late Pleistocene marine sediments around a shallow
      methane hydrate deposit in the Japan Sea.
AB  - Marine sediments contain eukaryotic DNA deposited from overlying water columns.
      However, a large proportion of deposited eukaryotic DNA is aerobically
      biodegraded in shallow marine sediments. Cold seep sediments are often anaerobic
      near the sediment-water interface, so eukaryotic DNA in such sediments is
      expected to be preserved. We investigated deeply buried marine sediments in the
      Japan Sea, where a methane hydrate deposit is associated with cold seeps.
      Quantitative PCR analysis revealed the reproducible recovery of eukaryotic DNA in
      marine sediments at depths up to 31.0 m in the vicinity of the methane hydrate
      deposit. In contrast, the reproducible recovery of eukaryotic DNA was limited to
      a shallow depth (8.3 m) in marine sediments not adjacent to the methane hydrate
      deposit in the same area. Pyrosequencing of an 18S rRNA gene variable region
      generated 1,276-3,307 reads per sample, which was sufficient to cover the
      biodiversity based on rarefaction curves. Phylogenetic analysis revealed that
      most of the eukaryotic DNA originated from radiolarian genera of the class
      Chaunacanthida, which have SrSO4 skeletons, the sea grass genus Zostera, and the
      seaweed genus Sargassum. Eukaryotic DNA originating from other planktonic fauna
      and land plants was also detected. Diatom sequences closely related to
      Thalassiosira spp., indicative of cold climates, were obtained from sediments
      deposited during the last glacial period (MIS-2). Plant sequences of the genera
      Alnus, Micromonas, and Ulmus were found in sediments deposited during the warm
      interstadial period (MIS-3). These results suggest the long-term persistence of
      eukaryotic DNA from terrestrial and aquatic sources in marine sediments
      associated with cold seeps, and that the genetic information from eukaryotic DNA
      from deeply buried marine sediments associated with cold seeps can be used to
      reconstruct environments and ecosystems from the past.

PMID- 28434199
TI  - Repeated evolution of digital adhesion in geckos: a reply to Harrington and
      Reeder.
AB  - We published a phylogenetic comparative analysis that found geckos had gained and
      lost adhesive toepads multiple times over their long evolutionary history (Gamble
      et al., PLoS One, 7, 2012, e39429). This was consistent with decades of
      morphological studies showing geckos had evolved adhesive toepads on multiple
      occasions and that the morphology of geckos with ancestrally padless digits can
      be distinguished from secondarily padless forms. Recently, Harrington & Reeder
      (J. Evol. Biol., 30, 2017, 313) reanalysed data from Gamble et al. (PLoS One, 7,
      2012, e39429) and found little support for the multiple origins hypothesis. Here,
      we argue that Harrington and Reeder failed to take morphological evidence into
      account when devising ancestral state reconstruction models and that these
      biologically unrealistic models led to erroneous conclusions about the evolution
      of adhesive toepads in geckos.

PMID- 28434200
TI  - Land use for animal production in global change studies: Defining and
      characterizing a framework.
AB  - Land use for animal production influences the earth system in a variety of ways,
      including local-scale modification to biodiversity, soils, and nutrient cycling;
      regional changes in albedo and hydrology; and global-scale changes in greenhouse
      gas and aerosol concentrations. Pasture is furthermore the single most extensive
      form of land cover, currently comprising about 22-26% of the earth's ice-free
      land surface. Despite the importance and variable expressions of animal
      production, distinctions among different systems are effectively absent from
      studies of land use and land cover change. This deficiency is improving; however,
      livestock production system classifications are rarely applied in this context,
      and the most popular global land cover inventories still present only a single,
      usually poorly defined category of "pasture" or "rangeland" with no
      characterization of land use. There is a marked lack of bottom-up, evidence-based
      methodology, creating a pressing need to incorporate cross-disciplinary evidence
      of past and present animal production systems into global change studies. Here,
      we present a framework, modified from existing livestock production systems, that
      is rooted in sociocultural, socioeconomic, and ecological contexts. The framework
      defines and characterizes the range of land usage pertaining to animal
      production, and is suitable for application in land use inventories and
      scenarios, land cover modeling, and studies on sustainable land use in the past,
      present, and future.

PMID- 28434201
TI  - How much alcohol is consumed outside of the lifetime risk guidelines in
      Australia?
AB  - INTRODUCTION AND AIMS: This study aims to estimate the prevalence of long-term
      risky drinking within the Australian population and the proportion of standard
      drinks that is consumed outside of the long-term risk (LTR) guidelines of two
      Australian standard drinks (ASD) per day. DESIGN AND METHODS: Recruited by phone,
      2020 Australian adults with an oversampling of risky drinkers were asked detailed
      questions about how much alcohol they consumed at a range of locations in 2013.
      Descriptive statistical analyses of data weighted to be representative of the
      Australian adult population were undertaken, with a focus on the ASD consumed
      above the LTR guidelines. RESULTS: Although 28% of respondents drink at levels
      above the LTR drinking guidelines, 56% of all ASD consumed are above the two per
      day recommended to reduce LTR. Three-quarters of cask wine and liqueurs were
      consumed outside of the LTR guidelines, as were 58% of all ASD consumed in the
      home, similar to the proportion of ASD consumed above the guidelines in pubs
      (55%). DISCUSSION AND CONCLUSIONS: While the minority of Australians drink to LTR
      levels, the majority of alcohol is consumed by long-term risky drinkers. More
      research and policy focus on the patterns of alcohol consumption that lead to
      long-term risk, particularly outside of licensed premises, is required. [Callinan
      S, Livingston M, Room R, Dietze PM. How much alcohol is consumed outside of the
      lifetime risk guidelines in Australia?. Drug Alcohol Rev 2018;37:42-47].

PMID- 28434202
TI  - Distribution of norovirus genotypes and subtypes in river water by ultra-deep
      sequencing-based analysis.
AB  - : To determine the distribution of Norovirus (NoV) genotypes in natural river
      water in Thailand, we conducted a genome analysis using a next-generation
      sequencer. Twenty-five river water samples were collected at five different sites
      of the Khlong Klon River in the suburbs of Bangkok between August 2013 and
      December 2014. The partial genome of NoV was detected in 15 of the 25 samples
      (60.0%). Seven of these 15 samples (46.7%) contained multiple NoV GII genotypes:
      GII.4, GII.6, and GII.17. Our data showed that GII.17 had already emerged in
      August 2013 as a minor population, and it became a major genotype in December
      2014. Our findings indicate that the virus was likely to have been circulating in
      the community before it appeared in the river water. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Our study was to investigate the frequencies of multiple genogroups
      and genotypes of norovirus in the river water near Bangkok, Thailand, by ultra
      deep sequencing-based analysis. This study revealed that the epidemic strain was
      likely to have been circulating in the community before it appeared in the river
      water. Monitoring of the Norovirus (NoV) genomes in the natural environment may
      contribute to an understanding of the emergence of new epidemic NoV strains in
      human populations.

PMID- 28434203
TI  - Topiramate monotherapy for juvenile myoclonic epilepsy.
AB  - BACKGROUND: Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some
      studies have shown the benefits of topiramate monotherapy in the treatment of
      juvenile myoclonic epilepsy (JME). However, there are no current systematic
      reviews to determine the efficacy and tolerability of topiramate monotherapy in
      people with JME. This is an updated version of the original Cochrane Review
      published in Issue 12, 2015. OBJECTIVES: To evaluate the efficacy and
      tolerability of topiramate monotherapy in the treatment of JME. SEARCH METHODS:
      For the latest update, on 21 February 2017 we searched Cochrane Epilepsy's
      Specialized Register, CENTRAL, MEDLINE, and ClinicalTrials.gov. We also searched
      ongoing trials registers, reference lists and relevant conference proceedings,
      and contacted study authors and pharmaceutical companies. SELECTION CRITERIA: We
      included randomized controlled trials (RCTs) investigating topiramate monotherapy
      versus placebo or other AED treatment for people with JME, with the outcomes of
      proportion of responders or experiencing adverse events (AEs). DATA COLLECTION
      AND ANALYSIS: Two review authors independently screened the titles and abstracts
      of identified records, selected studies for inclusion, extracted data, cross
      checked the data for accuracy and assessed the methodological quality. We
      performed no meta-analyses due to the limited available data. MAIN RESULTS: We
      included three studies with 83 participants. For efficacy, a greater proportion
      of participants in the topiramate group had a 50% or more reduction in primarily
      generalized tonic-clonic seizures (PGTCS) compared with participants in the
      placebo group. There were no significant differences between topiramate versus
      valproate in participants responding with a 50% or more reduction in myoclonic
      seizures or in PGTCS or seizure-free. Concerning tolerability, we ranked AEDs
      associated with topiramate as moderate-to-severe, while we ranked 59% of AEDs
      linked to valproate as severe complaints. Moreover, systemic toxicity scores were
      higher in the valproate group than the topiramate group. We judged the quality of
      the evidence from the studies to be very low. AUTHORS' CONCLUSIONS: Since the
      last version of this review we found no new studies. This review does not provide
      sufficient evidence to support topiramate for the treatment of people with JME.
      Based on the current limited available data, topiramate seems to be better
      tolerated than valproate, but there were no more benefits of efficacy in
      topiramate compared with valproate. In the future, well-designed, double-blind
      RCTs with large samples are required to test the efficacy and tolerability of
      topiramate in people with JME.

PMID- 28434204
TI  - Positive airway pressure adherence and mask interface in the setting of sinonasal
      symptoms.
AB  - OBJECTIVES/HYPOTHESIS: Despite reports of lower positive pressure adherence rates
      with oronasal masks, patients with sinonasal problems are often prescribed this
      interface over a nasal interface. The aim of this study was to characterize the
      relationship between mask type and therapy adherence in the setting of sinonasal
      symptoms. STUDY DESIGN: Retrospective case series with chart review. METHODS: We
      reviewed 328 patients who underwent positive pressure titration between January
      2012 and May 2015. Follow-up adherence data were available for 218 patients
      (66.5%). Multivariate analysis examined whether patients with sinonasal symptoms
      have improved adherence with oronasal masks compared to nasal or nasal pillow
      interfaces. RESULTS: At a median follow-up of 95 days, positive pressure
      adherence in patients with sinonasal symptoms was highest with the nasal pillow
      interface. When compared with oronasal interfaces, the odds of adequate therapy
      adherence were >5 times greater with nasal pillow interfaces (odds ratio [OR] =
      5.20, 95% confidence interval [CI] = 1.61-16.80, P = .006) and >3 times greater
      with nasal interfaces (OR = 3.67, 95% CI = 1.20-11.26, P = .02) in these
      symptomatic patients. CONCLUSIONS: The presence of nasal problems does not
      predict the need for an oronasal mask. Positive pressure adherence rates are
      higher with nasal and nasal pillow interfaces compared to oronasal masks, even in
      patients with sinonasal complaints. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2418
      2422, 2017.

PMID- 28434205
TI  - Molecular systematics reveals increased diversity within the South African
      Laurencia complex (Rhodomelaceae, Rhodophyta).
AB  - Previous publications list ten species in the Laurencia complex from South Africa
      with all ascribed to the genus Laurencia sensu stricto. However, the diversity of
      the complex in South Africa has not yet been re-assessed following the numerous
      recent taxonomic changes. This study investigated the phylogenetic relationships
      and taxonomy of this group in South Africa using recent collections. Methods
      included molecular phylogenetic analyses of plastid rbcL gene sequences (a total
      of 146; including eleven outgroup taxa) using Maximum Likelihood and Bayesian
      Inference, and the examination of morphological and anatomical characters,
      including the number of corps en cerise when present. The seven genera of the
      Laurencia complex formed monophyletic clades with high posterior probabilities.
      Seventeen morphotypes were identified: 14 in the genus Laurencia sensu stricto,
      among which eight corresponded to Laurencia species currently recognized from
      South Africa and one each to species of Palisada, Chondrophycus, and
      Laurenciella. The six remaining morphotypes in Laurencia sensu stricto did not
      match any descriptions and are described here as five new species: Laurencia
      alfredensis sp. nov., Laurencia dichotoma sp. nov., Laurencia digitata sp. nov.,
      Laurencia multiclavata sp. nov. and Laurencia sodwaniensis sp. nov. and a new
      variety: Laurencia pumila var. dehoopiensis var. nov. Laurencia stegengae nom.
      nov. is established to replace Laurencia peninsularis Stegenga, Bolton and
      Anderson nom. illeg. The diversity is likely greater, with six additional
      unidentified specimens found in this molecular investigation. These findings
      place South Africa alongside Australia in having one of the most diverse floras
      of this group in the world.

PMID- 28434206
TI  - A phylogeographic investigation of the kelp genus Laminaria (Laminariales,
      Phaeophyceae), with emphasis on the South Atlantic Ocean.
AB  - The genus Laminaria has a wide distribution range compared with other kelp genera
      because it is found in both the North and the South Atlantic, on both sides of
      the North Pacific, as well as in the Mediterranean. Hypotheses behind this
      biogeographical pattern have been discussed by several authors but have not yet
      been fully evaluated with time-calibrated phylogenies. Based on the analysis of
      four molecular markers (ITS2, rbcL, atp8 and trnWI), our goal was to reassess the
      Laminaria species diversity in South Africa, assess its relationship with the
      other species distributed in the South Atlantic and reconstruct the historical
      biogeography of the genus. Our results confirm the occurrence of a single
      species, L. pallida, in southern Africa, and its sister relationship with the
      North Atlantic L. ochroleuca. Both species belonged to a clade containing the
      other South Atlantic species: L. abyssalis from Brazil, and the Mediterranean L.
      rodriguezii. Our time-calibrated phylogenies suggest that Laminaria originated in
      the northern Pacific around 25 mya, followed by at least two migration events
      through the Bering Strait after its opening (~5.32 mya). Today, the first is
      represented by L. solidungula in the Arctic, while the second gave rise to the
      rest of the Atlantic species. The colonization of the North Atlantic was followed
      by a gradual colonization southward along the west coast of Europe, into the
      Mediterranean (~2.07 mya) and two recent, but disconnected, migrations (~1.34 and
      0.87 mya) across the equator, giving rise to L. abyssalis in Brazil and L.
      pallida in southern Africa, respectively.

PMID- 28434207
TI  - Maternal rates of lipolysis and glucose production in late pregnancy are
      independently related to foetal weight.
AB  - OBJECTIVE: Associations between maternal glucose levels and increased foetal
      growth are well established, and independent relationships with maternal weight,
      weight gain and insulin resistance are also observed. The relative roles of
      lipolysis and glucose production in the determination of these observations
      remain unclear. DESIGN: We examined, through detailed physiological studies, the
      relationship between maternal late gestational energy substrate production
      (glucose and glycerol), maternal weight and weight gain, and estimated foetal
      size in the third trimester. PATIENTS: Twenty-one nulliparous pregnant women,
      without gestational diabetes (GDM) assessed at 28 weeks with oral glucose
      tolerance test, were recruited. MEASUREMENTS: Rates of hepatic glucose production
      (GPR) and rates of glycerol production (reflecting lipolysis) using [13 C6 ]
      glucose and [2 H5 ]-glycerol were measured at 34-36 weeks of gestation.
      Respiratory quotient was assessed by indirect calorimetry and body composition by
      measurements of total body water (TBW; H218 O) and body density (BODPOD). Foetal
      weight was estimated from ultrasound measures of biparietal diameter, femoral
      length and abdominal circumference. RESULTS: At 34-36 weeks, bivariate analyses
      showed that GPR and lipolysis correlated with estimated foetal weight (r=.71 and
      .72, respectively) as well as with maternal weight, fat mass and fat-free mass,
      but not maternal weight gain. In multivariate analyses, rates of both glucose
      production (r=.42) and lipolysis (r=.47) were independently associated with
      foetal size explaining 63% of the variance. CONCLUSIONS: Both maternal rates of
      lipolysis and hepatic glucose production in late gestation are strongly related
      to estimated foetal weight.

PMID- 28434208
TI  - Dietary interventions for adults with chronic kidney disease.
AB  - BACKGROUND: Dietary changes are routinely recommended in people with chronic
      kidney disease (CKD) on the basis of randomised evidence in the general
      population and non-randomised studies in CKD that suggest certain healthy eating
      patterns may prevent cardiovascular events and lower mortality. People who have
      kidney disease have prioritised dietary modifications as an important treatment
      uncertainty. OBJECTIVES: This review evaluated the benefits and harms of dietary
      interventions among adults with CKD including people with end-stage kidney
      disease (ESKD) treated with dialysis or kidney transplantation. SEARCH METHODS:
      We searched the Cochrane Kidney and Transplant Specialised Register (up to 31
      January 2017) through contact with the Information Specialist using search terms
      relevant to this review. Studies contained in the Specialised Register are
      identified through search strategies specifically designed for CENTRAL, MEDLINE,
      and EMBASE; handsearching conference proceedings; and searching the International
      Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised RCTs of dietary
      interventions versus other dietary interventions, lifestyle advice, or standard
      care assessing mortality, cardiovascular events, health-related quality of life,
      and biochemical, anthropomorphic, and nutritional outcomes among people with CKD.
      DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for
      inclusion and extracted data. Results were summarised as risk ratios (RR) for
      dichotomous outcomes or mean differences (MD) or standardised MD (SMD) for
      continuous outcomes, with 95% confidence intervals (CI) or in descriptive format
      when meta-analysis was not possible. Confidence in the evidence was assessed
      using GRADE. MAIN RESULTS: We included 17 studies involving 1639 people with CKD.
      Three studies enrolled 341 people treated with dialysis, four studies enrolled
      168 kidney transplant recipients, and 10 studies enrolled 1130 people with CKD
      stages 1 to 5. Eleven studies (900 people) evaluated dietary counselling with or
      without lifestyle advice and six evaluated dietary patterns (739 people),
      including one study (191 people) of a carbohydrate-restricted low-iron,
      polyphenol enriched diet, two studies (181 people) of increased fruit and
      vegetable intake, two studies (355 people) of a Mediterranean diet and one study
      (12 people) of a high protein/low carbohydrate diet. Risks of bias in the
      included studies were generally high or unclear, lowering confidence in the
      results. Participants were followed up for a median of 12 months (range 1 to 46.8
      months).Studies were not designed to examine all-cause mortality or
      cardiovascular events. In very-low quality evidence, dietary interventions had
      uncertain effects on all-cause mortality or ESKD. In absolute terms, dietary
      interventions may prevent one person in every 3000 treated for one year avoiding
      ESKD, although the certainty in this effect was very low. Across all 17 studies,
      outcome data for cardiovascular events were sparse. Dietary interventions in low
      quality evidence were associated with a higher health-related quality of life (2
      studies, 119 people: MD in SF-36 score 11.46, 95% CI 7.73 to 15.18; I2 = 0%).
      Adverse events were generally not reported.Dietary interventions lowered systolic
      blood pressure (3 studies, 167 people: MD -9.26 mm Hg, 95% CI -13.48 to -5.04; I2
      = 80%) and diastolic blood pressure (2 studies, 95 people: MD -8.95, 95% CI 
      10.69 to -7.21; I2 = 0%) compared to a control diet. Dietary interventions were
      associated with a higher estimated glomerular filtration rate (eGFR) (5 studies,
      219 people: SMD 1.08; 95% CI 0.26 to 1.97; I2 = 88%) and serum albumin levels (6
      studies, 541 people: MD 0.16 g/dL, 95% CI 0.07 to 0.24; I2 = 26%). A
      Mediterranean diet lowered serum LDL cholesterol levels (1 study, 40 people: MD 
      1.00 mmol/L, 95% CI -1.56 to -0.44). AUTHORS' CONCLUSIONS: Dietary interventions
      have uncertain effects on mortality, cardiovascular events and ESKD among people
      with CKD as these outcomes were rarely measured or reported. Dietary
      interventions may increase health-related quality of life, eGFR, and serum
      albumin, and lower blood pressure and serum cholesterol levels.Based on
      stakeholder prioritisation of dietary research in the setting of CKD and
      preliminary evidence of beneficial effects on risks factors for clinical
      outcomes, large-scale pragmatic RCTs to test the effects of dietary interventions
      on patient outcomes are required.

PMID- 28434209
TI  - Urine clusterin/apolipoprotein J is linked to tubular damage and renal outcomes
      in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: The objective of this study was to evaluate the association of urine
      clusterin/apolipoprotein J (Apo J) with the development and/or progression of
      diabetic kidney disease (DKD) in type 2 diabetes. MATERIALS AND METHODS: A total
      of 159 type 2 diabetic patients and 20 nondiabetic subjects with estimated
      glomerular filtration rate (eGFR) >=60 mL/min/1.73 m2 were enrolled. The baseline
      values of urine clusterin and tubular damage markers were measured. The primary
      outcome was the annual decline rate in eGFR, and secondary outcomes were the
      development of chronic kidney disease (CKD) stage 3 or greater and the
      persistence/progression of albuminuria. The median follow-up duration of enrolled
      patients was 3.0 (1.0-5.9) years. RESULTS: Baseline clusterin levels in urine
      were significantly increased in type 2 diabetic subjects compared with those of
      nondiabetic subjects. The levels of urine clusterin had a significant correlation
      with urine tubular damage markers. A positive correlation between the annual rate
      of decline in eGFR and urine clusterin after adjusting for clinical confounding
      factors was detected. Multivariate analysis further indicated that urine
      clusterin correlated with the development of CKD stage 3 or greater and
      persistence/progression of albuminuria. In type 2 diabetic subjects with
      albuminuria, urine clusterin remained associated with the annual decline rate in
      eGFR and the progression of CKD stage. CONCLUSIONS: Urine clusterin reflects
      tubular damage in the early stage of DKD. The increase in urine clusterin along
      with albuminuria could be an independent predictive marker for the progression of
      DKD in type 2 diabetes.

PMID- 28434210
TI  - Changes in perinatal hospital deaths occurring outside the neonatal intensive
      care unit over a decade.
AB  - AIM: Perinatal deaths occurring outside the neonatal intensive care unit (NICU)
      are rarely recorded in outcome studies, despite having a direct impact on
      perinatal statistics. Our aim was to investigate the timing and modes of
      perinatal deaths that occurred outside the NICU and changes over time. METHOD: We
      reviewed all perinatal deaths from 22 weeks of gestation onwards, without NICU
      admissions, during two periods in a Canadian tertiary mother and baby hospital
      and categorised deaths according to nine specific categories. RESULTS: There were
      444 perinatal deaths that satisfied the inclusion criteria. The total number of
      perinatal deaths increased from 2000 to 2002 (n = 197) and 2007 to 2010 (n =
      247). The proportion of foetuses alive at the time of their mother's hospital
      admission, but then stillborn, decreased. There was a significant increase in
      terminations for congenital anomalies in the second cohort and a decrease in
      deaths following induction of labour and comfort care for foetal anomalies.
      CONCLUSION: Approaches to end-of-life care changed between the two study periods.
      Paediatricians should be aware of the epidemiology of perinatal mortality in
      their own practice, as it has a direct impact on the denominator in NICU outcome
      studies.

PMID- 28434212
TI  - Effects of Environmental Factors on Cyanobacterial Production of Odorous
      Compounds: Geosmin and 2-Methylisoborneol.
AB  - Geosmin and 2-methylisoborneol (2-MIB), responsible for earthy or musty smell,
      are a major concern for safe drinking water supplies. This study investigated the
      effects of environmental factors on odorous compound production and cell growth
      in cyanobacterial strains. Anabaena sp. FACHB-1384, a 2-MIB producer, was
      sensitive to low temperature (<20 degrees C). However, geosmin producers,
      Anabaena sp. Chusori and Anabaena sp. NIER, were sensitive to high light
      intensity (>100 MUmol/m2/sec), but not to low temperature. Geosmin concentrations
      increased under higher nitrate concentrations, being linearly proportional to
      cell density. A P-limited chemostat showed that P-stress decreased the geosmin
      productivity and extracellular geosmin amount per cell in Anabaena sp. NIER.
      However, only 2-MIB productivity was reduced in Planktothrix sp. FACHB-1374 under
      P-limitation. The extracellular 2-MIB amount per cell remained constant at all
      dilution rates. In conclusion, high light intensity and P-stress can contribute
      to the lower incidence of geosmin, whereas 2-MIB reduction could be attainable at
      a lower temperature.

PMID- 28434211
TI  - Health conditions and motivations for marijuana use among young adult medical
      marijuana patients and non-patient marijuana users.
AB  - INTRODUCTION: While marijuana has been legal for medical purposes in California
      since 1996, little is known about the health histories of young adult medical
      marijuana patients who are a significant proportion of medical marijuana
      patients. We examined whether young adult medical marijuana patients reported
      health conditions and motivations for use that were consistent with medical use
      of marijuana in California. METHODS: Young adults (N = 366) aged 18 to 26 years
      were sampled in Los Angeles in 2014-2015 and segmented into medical marijuana
      'patients' (n = 210), marijuana users with a current recommendation, and non
      patient users or 'non-patients' (n = 156), marijuana users who never had a
      medical marijuana recommendation. Differences between patients and non-patients
      regarding self-reported health histories and past/current motivations for
      marijuana use were expressed as unadjusted risk ratios. RESULTS: Compared with
      non-patients, patients were significantly more likely to report a range of
      lifetime health problems, such as psychological, physical pain and
      gastrointestinal. In the past 90 days, patients were significantly more likely to
      report motivations for marijuana use than non-patients concerning sleep, anxiety,
      physical pain and focusing. Psychological and pain problems were the most common
      health conditions reported to receive a medical marijuana recommendation.
      Patients were significantly less likely than non-patients to report any privacy
      concerns about obtaining a medical marijuana recommendation. CONCLUSIONS:
      Patients were significantly more likely to report a range of health conditions
      and motivations associated with medical use than non-patients. A great majority
      of patients reported obtaining a medical marijuana recommendation for health
      problems in accordance with the California law. [Lankenau SE, Ataiants J,Mohanty
      S, Schrager S, Iverson E, Wong CF.Health conditions and motivations for marijuana
      use among young adultmedical marijuana patients and non-patient marijuana users.
      Drug Alcohol Rev 2017;00:000-000].

PMID- 28434213
TI  - Evaluation of the Synergistic Effect of Mixed Cultures of White-Rot Fungus
      Pleurotus ostreatus and Biosurfactant-Producing Bacteria on DDT Biodegradation.
AB  - DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane) is one of the organic
      synthetic pesticides that has many negative effects for human health and the
      environment. The purpose of this study was to investigate the synergistic effect
      of mixed cutures of white-rot fungus, Pleurotus ostreatus, and biosurfactant
      producing bacteria, Pseudomonas aeruginosa and Bacillus subtilis, on DDT
      biodegradation. Bacteria were added into the P. ostreatus culture (mycelial wet
      weight on average by 8.53 g) in concentrations of 1, 3, 5, and 10 ml (1 ml ~ 1.25
      * 109 bacteria cells/ml culture). DDT was degraded to approximately 19% by P.
      ostreatus during the 7-day incubation period. The principal result of this study
      was that the addition of 3 ml of P. aeruginosa into P. ostreatus culture gave the
      highest DDT degradation rate (approximately 86%) during the 7-day incubation
      period. This mixed culture combination of the fungus and bacteria also gave the
      best ratio of optimization of 1.91. DDD (1,1-dichloro-2,2-bis(4-chlorophenyl)
      ethane), DDE (1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene), and DDMU (1-chloro
      2,2-bis(4-chlorophenyl) ethylene) were detected as metabolic products from the
      DDT degradation by P. ostreatus and P. aeruginosa. The results of this study
      indicate that P. aeruginosa has a synergistic relationship with P. ostreatus and
      can be used to optimize the degradation of DDT by P. ostreatus.

PMID- 28434214
TI  - Chitinimonas naiadis sp. nov., Isolated from a Freshwater River.
AB  - A rod shaped, aerobic, Gram-stain-negative, and motile bacterium, strain AR2T,
      was isolated from a water sample of Yeongsan river, Republic of Korea. Strain
      AR2T clustered closely with the members of the genus Chitinimonas and showed the
      highest 16S rRNA gene sequence similarity with Chitinimonas prasina LY03T
      (96.4%), Chitinimonas viridis HMD2169T (96.4%), Chitinimonas taiwanensis cfT
      (96.2%), and Chitinimonas koreensis R2A43-10T (94.2%). The predominant fatty
      acids of strain AR2T were identified to be summed feature 3 (comprising
      C16:1omega7c and/or C16:1omega6c), C16:0, and C10:03-OH. Diphosphatidylglycerol,
      phosphatidylglycerol, and phosphatidylethanolamine were found to be the major
      polar lipids. The genomic DNA G+C content was 60.4 mol%. Based on the polyphasic
      characterization, the isolated strain AR2T is described as a representative of a
      novel species in the genus Chitinimonas, for which the name Chitinimonas naiadis
      sp. nov. (type strain =AR2T =KCTC 42755T =JCM 31504T) is proposed.

PMID- 28434215
TI  - Long-Term Survival in Stage IV Esophageal Adenocarcinoma with Chemoradiation and
      Serial Endoscopic Cryoablation.
AB  - Esophageal cancer has a poor overall prognosis and is frequently diagnosed at a
      late stage. Conventional treatment for metastatic esophageal cancer involves
      chemotherapy and radiation. Local disease control plays a significant role in
      improving survival. Endoscopic spray cryotherapy is a novel modality that
      involves freezing and thawing to produce local ablation of malignant tissue via
      ischemic mechanisms. Spray cryotherapy has been shown to be effective,
      particularly for early T-stage, superficial esophageal adenocarcinomas. We
      present the case of a 72-year-old-male with locally recurrent stage IV esophageal
      adenocarcinoma and long-term survival of 7 years to date, with concurrent
      chemoradiation and serial cryoablation. He remains asymptomatic and continues to
      undergo chemotherapy and sequential cryoablation. The findings highlight the long
      term safety and efficacy of cryotherapy in combination with chemoradiation, and
      suggest that cryoablation may have an additive role in the treatment of advanced
      stage esophageal adenocarcinoma.

PMID- 28434217
TI  - Bilateral Hypoplasia of the Medial and Lateral Menisci.
AB  - Hypoplasia of the meniscus is a very rare congenital abnormality, with only a few
      cases reported to date. A 9-year-old girl visited our hospital due to lateral
      knee pain following a hyperextension injury to the left knee. Magnetic resonance
      imaging showed hypoplasia of the medial and lateral menisci, as well as a
      posterior horn tear of the lateral meniscus, in both knee joints. To our
      knowledge, this is the first report of a patient with hypoplasia of the medial
      and lateral menisci in both knee joints.

PMID- 28434216
TI  - Can Endoscopic Ulcerations in Early Gastric Cancer Be Clearly Defined before
      Endoscopic Resection? A Survey among Endoscopists.
AB  - BACKGROUND/AIMS: Early gastric cancer (EGC) with ulcerations can be treated via
      endoscopic resection (ER) when it is differentiated pathologically, limited to
      the mucosa, and <3 cm in diameter. The presence of ulceration is a key factor in
      deciding treatment strategies and is usually diagnosed during endoscopic
      examination. The aim of this study was to evaluate whether ulcerations in EGC can
      be clearly defined among endoscopists and which factors are related to the
      differences. METHODS: A survey questionnaire, composed of demographic features
      and endoscopic images of seven patients with EGC, was presented to the
      endoscopists via e-mail. The endoscopists were asked whether such patients have
      ulcerations in the lesions. RESULTS: The questionnaires were e-mailed to 197
      endoscopists, and 103 doctors replied. The presence of an endoscopic ulceration
      was defined differently among the endoscopists, depending on the duration of
      endoscopic practice and the experience of endoscopic submucosal dissection. The
      differences were especially high in the lesions without mucosal breaks and
      converging folds, which were expected to be viewed as non-ulcerative.
      CONCLUSIONS: Before ER, endoscopic ulcerations in EGC must be reviewed by
      experienced endoscopists to reduce overestimations, and adequate educational
      programs for trainees should be established.

PMID- 28434218
TI  - [Urinary tract infection by Lactobacillus delbrueckii, microorganism used as
      probiotic].

PMID- 28434219
TI  - Hydrogen Peroxide-Responsive Nanoprobe Assists Circulating Tumor Cell
      Identification and Colorectal Cancer Diagnosis.
AB  - In the clinic, numeration of circulating tumor cells (CTCs) plays a critical role
      in cancer diagnosis and treatment, but conventional CTC identification and
      counting that rely on specific antibodies to characterize a cell's surface
      antigens are costive and with limitations. Importantly, false positive or
      negative results may occur due to the high heterogeneity and epithelial
      mesenchymal transition (EMT) of CTCs. Herein we demonstrate a novel and effective
      CTC detecting nanoprobe that could rapidly respond to the high level of
      endogenous H2O2 of CTCs and report the signal through fluorescence emission.
      Briefly, a hydrophobic coumarin-benzene boronic acid pinacol ester (Cou-Bpin) was
      grafted onto hydrophilic glycol chitosan (GC) to form an amphiphilic molecule,
      which further assembled into micellar nanoparticles in aqueous solution. This new
      nanoprobe was highly sensitive to H2O2 with a detection limit of 0.1 MUM and
      could rapidly enter the cells within 30 min. Upon exposure to intracellular H2O2,
      the nanoprobe exhibited remarkable one-photon and two-photon luminescent
      characteristics, which were suitable for imaging of endogenous H2O2 of various
      human colorectal cancer cells and assist the identification of CTCs. Compared to
      a conventional CTC counting assay, the nanoprobe-based CTC numeration could
      overcome the false-negative findings due to the low expression of cytokeratin 19
      (CK19). In a clinic test, CTC counting results based on the new nanoprobe match
      better to the postoperative pathological results of four clinic patients who had
      colorectal cancer at different stages.

PMID- 28434220
TI  - Effects of the Backbone and Chemical Linker on the Molecular Conductance of
      Nucleic Acid Duplexes.
AB  - Scanning tunneling microscope break junction measurements are used to examine how
      the molecular conductance of nucleic acids depends on the composition of their
      backbone and the linker group to the electrodes. Molecular conductances of 10
      base pair long homoduplexes of DNA, aeg-PNA, gamma-PNA, and a heteroduplex of
      DNA/aeg-PNA with identical nucleobase sequence were measured. The molecular
      conductance was found to vary by 12 to 13 times with the change in backbone.
      Computational studies show that the molecular conductance differences between
      nucleic acids of different backbones correlate with differences in backbone
      structural flexibility. The molecular conductance was also measured for duplexes
      connected to the electrode through two different linkers, one directly to the
      backbone and one directly to the nucleobase stack. While the linker causes an
      order-of-magnitude increase in the overall conductance for a particular duplex,
      the differences in the electrical conductance with backbone composition are
      preserved. The highest molecular conductance value, 0.06G0, was measured for aeg
      PNA duplexes with a base stack linker. These findings reveal an important new
      strategy for creating longer and more complex electroactive, nucleic acid
      assemblies.

PMID- 28434221
TI  - Characterization of Mesocarp and Kernel Lipids from Elaeis guineensis Jacq.,
      Elaeis oleifera [Kunth] Cortes, and Their Interspecific Hybrids.
AB  - Morphological traits, total lipid contents, and fatty acid profiles were assessed
      in fruits of several accessions of Elaeis oleifera [Kunth] Cortes, Elaeis
      guineensis Jacq., and their interspecific hybrids. The latter featured the
      highest mesocarp-to-fruit ratios (77.9-78.2%). The total lipid contents of both
      E. guineensis mesocarp and kernel were significantly higher than for E. oleifera
      accessions. Main fatty acids comprised C16:0, C18:1n9, and C18:2n6 in mesocarp
      and C12:0, C14:0, and C18:1n9 in kernels. E. oleifera samples were characterized
      by higher proportions of unsaturated long-chain fatty acids. Saturated medium
      chain fatty acids supported the clustering of E. guineensis kernels in
      multivariate statistics. Hybrid mesocarp lipids had an intermediate fatty acid
      composition, whereas their kernel lipids resembled those of E. oleifera
      genotypes. Principal component analysis based on lipid contents and proportions
      of individual fatty acids permitted clear-cut distinction of E. oleifera, E.
      guineensis, and their hybrids.

PMID- 28434222
TI  - Isomer-Specific Transplacental Transfer of Perfluoroalkyl Acids: Results from a
      Survey of Paired Maternal, Cord Sera, and Placentas.
AB  - Currently, information regarding isomer-specific concentrations of PFHxS, PFOS,
      and PFOA in human placenta, and corresponding placental-maternal ratios (RPM) of
      these compounds does not exist. The objective of the present study was to assess
      the occurrence, and distribution of different PFHxS, PFOS, and PFOA isomers in
      maternal serum, umbilical cord serum, and placenta to gain a better understanding
      of transplacental transport efficiency and prenatal exposure risks. The study
      involved quantitative determination of isomer-specific concentrations of PFHxS,
      PFOS, and PFOA in samples of maternal serum (n = 32), cord serum (n = 32), and
      placenta (n = 32) from pregnant women in Wuhan, China. The results indicate that
      both linear and branched PFHxS, PFOS and PFOA can be efficiently transported
      across the placenta, with exposure levels ordered maternal serum > cord serum >
      placenta. For PFOS isomers, the concentration ratios between cord serum and
      maternal serum (RCM) were ordered n < iso < 4m < (3 + 5)m < 1m < ?m2. The RPM
      values exhibited a similar trend for branched PFOS isomers: iso < 4m ~ (3 + 5)m <
      1m ~ ?m2. Conversely, PFOA isomers did not exhibit an obvious structure-activity
      relationship for RCM and RPM. n-PFHxS transported across the placenta to a
      greater extent than br-PFHxS. To the best of our knowledge, this is the first
      study to report the occurrence of PFHxS, PFOS, and PFOA isomers in human
      placenta. Further, RPM values of these compounds are reported here for the first
      time. The findings help to better understand the mechanisms of the placental
      transfer and neonatal exposure to these important contaminants of concern.

PMID- 28434223
TI  - Ultraclean Single Photon Emission from a GaN Quantum Dot.
AB  - Wide bandgap III-nitride quantum dots (QDs) are promising materials for the
      realization of solid-state single-photon sources, especially operating at room
      temperature. However, so far a large degree of inhomogeneous broadening induced
      by spectral diffusion has compromised their use. Here, we demonstrate the
      ultraclean emission from single GaN QDs formed at macrostep edges in a GaN/AlGaN
      quantum well. As a likely consequence of the high growth temperature and hence a
      reduced defect density, spectral diffusion is heavily suppressed to levels at
      least 1 order of magnitude lower than conventional GaN QDs. A record narrow line
      width of as small as 87 MUeV is obtained, while the low inhomogeneous broadening
      enables us to assess an upper limit of homogeneous broadening in the QDs (27
      MUeV). Furthermore, the uncontaminated emission facilitates the generation of
      ultraviolet single-photons with unprecedented purity (g(2)(0) = 0.02). The
      realization of high-quality GaN QDs will enable exploration of optoelectronic
      properties of III-nitrides, opening up the possibility of realizing single-photon
      quantum information systems operating at room temperature.

PMID- 28434224
TI  - Modeling Coordination-Directed Self-Assembly of M2L4 Nanocapsule Featuring
      Competitive Guest Encapsulation.
AB  - Exploring the mechanism of self-assembly and guest encapsulation of nanocapsules
      is highly imperative for the design of sophisticated molecular containers and
      multistimuli-responsive functional materials. Here we present a molecular
      dynamics simulation protocol with implicit solvent and simulated annealing
      techniques to investigate the self-assembly and competitive guest (C60 and C70
      fullerenes) encapsulation of a M2L4 nanocapsule that is self-assembled by the
      coordination of mercury cations and bent bidentate ligands. Stepwise formation of
      the nanocapsule and competitive fullerene encapsulation during dynamic structural
      changes in the self-assembly were detected successfully. Such processes were
      driven by coordination bonding and pi-pi stacking and obey the minimum total
      potential energy principle. Potential of mean force calculations for guest
      binding to the M2L4 nanocapsule explained the mechanism underlying the
      competitive encapsulations of C60 and C70. This work helps design new functional
      nanomaterials capable of guest encapsulation and release.

PMID- 28434225
TI  - In-Depth Proteome Coverage by Improving Efficiency for Membrane Proteome
      Analysis.
AB  - Although great achievement has been made in the mapping of human proteome, the
      efficiency of sample preparation still needs to be improved, especially for
      membrane proteins. Herein, we presented a novel method to deepen proteome
      coverage by the sequential extraction of proteins using urea and 1-dodecyl-3-
      methylimidazolium chloride (C12Im-Cl). With such a strategy, the commonly lost
      hydrophobic proteins by 8 M urea extraction could be further recovered by C12Im
      Cl, as well as the suppression effect of high abundance soluble proteins could be
      decreased. Followed by the in situ sample preparation and separation with
      different stationary phases, more than 9810 gene products could be identified,
      covering 8 orders of magnitude in abundance, which was, to the best of our
      knowledge, the largest data set of HeLa cell proteome. Compared with previous
      work, not only the number of proteins identified was obviously increased, but
      also the analysis time was shortened to a few days. Therefore, we expect that
      such a strategy has great potential applications to achieve unprecedented
      coverage for proteome analysis.

PMID- 28434226
TI  - In Situ Microprobe Single-Cell Capillary Electrophoresis Mass Spectrometry:
      Metabolic Reorganization in Single Differentiating Cells in the Live Vertebrate
      (Xenopus laevis) Embryo.
AB  - Knowledge of single-cell metabolism would provide a powerful look into cell
      activity changes as cells differentiate to all the tissues of the vertebrate
      embryo. However, single-cell mass spectrometry technologies have not yet been
      made compatible with complex three-dimensional changes and rapidly decreasing
      cell sizes during early development of the embryo. Here, we bridge this
      technological gap by integrating capillary microsampling, microscale metabolite
      extraction, and capillary electrophoresis electrospray ionization mass
      spectrometry (CE-ESI-MS) to enable direct metabolic analysis of identified cells
      in the live frog embryo (Xenopus laevis). Microprobe CE-ESI-MS of <0.02% of the
      single-cell content allowed us to detect ~230 different molecular features
      (positive ion mode), including 70 known metabolites, in single dorsal and ventral
      cells in 8-to-32-cell embryos. Relative quantification followed by multivariate
      and statistical analysis of the data found that microsampling enhanced detection
      sensitivity compared to whole-cell dissection by minimizing chemical
      interferences and ion suppression effects from the culture media. In addition,
      higher glutathione/oxidized glutathione ratios suggested that microprobed cells
      exhibited significantly lower oxidative stress than those dissected from the
      embryo. Fast (5 s/cell) and scalable microsampling with minimal damage to cells
      in the 8-cell embryo enabled duplicate and triplicate metabolic analysis of the
      same cell, which surprisingly continued to divide to the 16-cell stage. Last, we
      used microprobe single-cell CE-ESI-MS to uncover previously unknown
      reorganization of the single-cell metabolome as the dorsal progenitor cell from
      the 8-cell embryo formed the neural tissue fated clone through divisions to the
      32-cell embryo, peering, for the first time, into the formation of metabolic
      single-cell heterogeneity during early development of a vertebrate embryo.

PMID- 28434227
TI  - How Proteins Aggregate Can Reduce Allergenicity: Comparison of Ovalbumins Heated
      under Opposite Electrostatic Conditions.
AB  - Heated foods are recommended for avoiding sensitization to food proteins, but
      depending on the physicochemical conditions during heating, more or less unfolded
      proteins aggregate differently. Whether the aggregation process could modulate
      allergenicity was investigated. Heating ovalbumin in opposite electrostatic
      conditions led to small (A-s, about 50 nm) and large (A-L, about 65 MUm)
      aggregates that were used to sensitize mice. The symptoms upon oral challenge and
      rat basophil leukemia degranulation with native ovalbumin differed on the basis
      of which aggregates were used during the sensitization. Immunoglobulin-E (IgE)
      production was significantly lower with A-s than with A-L. Although two common
      linear IgE-epitopes were found, the aggregates bound and cross-linked IgE
      similarly or differently, depending on the sensitizing aggregate. The ovalbumin
      aggregates thus displayed a lower allergenic potential when formed under
      repulsive rather than nonrepulsive electrostatic conditions. This further
      demonstrates that food structure modulates the immune response during the
      sensitization phase with some effects on the elicitation phase of an allergic
      reaction and argues for the need to characterize the aggregation state of
      allergens.

PMID- 28434228
TI  - Rapid Biodegradation of the Herbicide 2,4-Dichlorophenoxyacetic Acid by
      Cupriavidus gilardii T-1.
AB  - Phytotoxicity and environmental pollution of residual herbicides have caused much
      public concern during the past several decades. An indigenous bacterial strain
      capable of degrading 2,4-dichlorophenoxyacetic acid (2,4-D), designated T-1, was
      isolated from soybean field soil and identified as Cupriavidus gilardii. Strain T
      1 degraded 2,4-D 3.39 times more rapidly than the model strain Cupriavidus
      necator JMP134. T-1 could also efficiently degrade 2-methyl-4-chlorophenoxyacetic
      acid (MCPA), MCPA isooctyl ester, and 2-(2,4-dichlorophenoxy)propionic acid (2,4
      DP). Suitable conditions for 2,4-D degradation were pH 7.0-9.0, 37-42  degrees C,
      and 4.0 mL of inoculums. Degradation of 2,4-D was concentration-dependent. 2,4-D
      was degraded to 2,4-dichlorophenol (2,4-DCP) by cleavage of the ether bond and
      then to 3,5-dichlorocatechol (3,5-DCC) via hydroxylation, followed by ortho
      cleavage to cis-2-dichlorodiene lactone (CDL). The metabolites 2,4-DCP or 3,5-DCC
      at 10 mg L-1 were completely degraded within 16 h. Fast degradation of 2,4-D and
      its analogues highlights the potential for use of C. gilardii T-1 in
      bioremediation of phenoxyalkanoic acid herbicides.

PMID- 28434230
TI  - Single-Layer Graphene Membranes Withstand Ultrahigh Applied Pressure.
AB  - High mechanical strength is essential for pressure-driven membrane separations
      with nanoporous single-layer graphene, but its ability to withstand high
      pressures remains to be demonstrated. We monitored failure of centimeter-scale
      single-layer graphene membranes on porous supports subjected to high pressures.
      Consistent with theory, the membranes were found to withstand higher pressures
      when placed on porous supports with smaller pore diameters, but failure occurred
      over a surprisingly broad range of pressures, attributed to heterogeneous
      susceptibility to failure at wrinkles, defects, and slack in the suspended
      graphene. Remarkably, nonwrinkled areas withstood pressure exceeding 100 bar at
      which many kinds of membrane suffer from compaction. Our study shows that single
      layer graphene membranes can sustain ultrahigh pressure especially if the effect
      of wrinkles is isolated using supports with small pores and suggests the
      potential for the use of single-layer graphene in high-pressure membrane
      separations.

PMID- 28434229
TI  - Cell Cycle-Dependent Kinase Cdk9 Is a Postexposure Drug Target against Human
      Adenoviruses.
AB  - Human adenoviruses (HAdVs) infect respiratory, gastrointestinal, and urinary
      tracts and give rise to eye infections and epidemic keratoconjunctivitis (EKC).
      They persist in lymphoid tissue and cause morbidity and mortality in
      immunocompromised people. Treatments with significant postexposure efficacy are
      not available. Here, we report that inhibition of the cell cycle-dependent kinase
      9 (Cdk9) by RNA interference, or the compound flavopiridol, blocked infections
      with HAdV-C2/5, EKC-causing HAdV-D8/37, and progeny formation in human corneal
      epithelial and cancer cells. Flavopiridol abrogated the production of the
      immediate early viral transactivating protein E1A without affecting nuclear
      import of viral DNA. In morphometric plaque assays, the compound exhibited
      antiviral efficacy in both pre- and postexposure regimens with therapeutic
      indexes exceeding 10. The study identifies Cdk9 as a postexposure drug target
      against adenovirus infections in vitro and suggests that the clinically tested
      anticancer drug flavopiridol is a candidate for treating adenoviral EKC or
      adenovirus emergence upon immune suppression.

PMID- 28434231
TI  - Charge and Film Drainage of Colliding Oil Drops Coated with the Nonionic
      Surfactant C12E5.
AB  - The interaction forces between colliding tetradecane drops were measured in the
      presence of the nonionic surfactant pentaethylene glycol monododecyl ether
      (C12E5). The force behavior was measured in the range of premicellar compositions
      of the nonionic surfactant in various salt solutions and was consistent with the
      presence of a surface charge even though the surfactant was nonionic in nature.
      The surface potential of oil drops was found to decrease with an increase in
      C12E5 concentration. The measured electrophoretic mobilities and zeta potentials
      of emulsified tetradecane drops also decreased with an increase in the C12E5
      concentration. The surface potential decreased with an increase in the
      electrolyte at a constant C12E5 concentration, further confirming the presence of
      a charged oil-water interface. In addition to the charging behavior, the
      nonequilibrium film drainage between the tetradecane drops coated with C12E5 was
      also measured. In contrast to some existing experiments in the literature, it was
      found that oil drops coated with the nonionic surfactant were stable against
      coalescence, even when the drops were deformed on the order of their radii. These
      findings have significant implications on the stability of emulsions in food,
      personal care, and detergent industries.

PMID- 28434232
TI  - Modeling Bisolute Adsorption of Aromatic Compounds Based on Adsorbed Solution
      Theories.
AB  - A large number of organic contaminants are commonly found in industrial and
      municipal wastewaters. For proper unit design to remove contaminant mixtures by
      adsorption, multicomponent adsorption equilibrium models are necessary. The
      present work examined the applicability of Ideal Adsorbed Solution Theory (IAST),
      a prevailing thermodynamic model, and its derivatives, i.e., Segregated IAST
      (SIAST) and Real Adsorbed Solution Theory (RAST), to bisolute adsorption of
      organic compounds onto a hyper-cross-linked polystyrene resin, MN200. Both IAST
      and SIAST were found to be less accurate in fitting the experimental bisolute
      adsorption isotherms than RAST. RAST incorporated with an empirical four
      parameter equation developed in this work can fit the adsorbed phase activity
      coefficients, gammai, better than RAST combined with the Wilson equation or the
      Nonrandom two-liquid (NRTL) model. Moreover, two polyparameter linear free energy
      relationships were developed for the adsorption of a number of solutes at low
      concentrations in the presence of a major contaminant (4-methylphenol or
      nitrobenzene). Results show that these relationships have a great potential in
      predicting gammai of solutes when the adsorbed amounts are dominated by a major
      contaminant. To the best of our knowledge, this is the first study predicting
      gammai for bisolute adsorption based on molecular descriptors. Overall, our
      findings have proved a major step forward to accurately modeling multisolute
      adsorption equilibrium.

PMID- 28434233
TI  - Electrospinning Preparation of Nanostructured g-C3N4/BiVO4 Composite Films with
      an Enhanced Photoelectrochemical Performance.
AB  - Nanostructured g-C3N4/BiVO4 composite films with an enhanced photoelectrochemical
      (PEC) performance have been fabricated via the facile electrospinning technique.
      The g-C3N4 nanosheets can not only form heterojunctions with BiVO4 but also
      prevent the agglomeration of BiVO4, helping the formation of nanostructures. The
      as-prepared g-C3N4/BiVO4 films exhibit good coverage and stability. The PEC
      performance of the g-C3N4/BiVO4 films is much more enhanced compared with that
      for individual BiVO4 films because of the enhanced electron-hole separation. The
      photocurrent density is 0.44 mA/cm2 for g-C3N4/BiVO4 films at 0.56 V in the
      linear sweep current-voltage test, over 10 times higher than that of individual
      BiVO4 films (0.18 mA/cm2). The effects of the preparation conditions including
      the g-C3N4 content, collector temperature, calcination temperature, and
      electrospinning time on the PEC performance were investigated, and the reasons
      for the effects were proposed. The optimal preparation condition was with 3.9 wt
      % g-C3N4 content in the electrospinning precursor, 185  degrees C collector
      temperature, 450  degrees C calcination temperature, and 40 min electrospinning
      time. The excellent PEC performance and the facile preparation method suggest
      that the g-C3N4/BiVO4 films are good candidates in energy and environmental
      remediation area.

PMID- 28434234
TI  - Phages and immunomodulation.
AB  - In the past years, the microbiome and its role in the pathophysiology of diseases
      have gained great interest. The progress of our knowledge in this field opens
      completely novel prospects for treating disorders, including those which are most
      challenging to medicine today. Of special interest are studies on the
      interactions of the microbiome with the immune system. Only recently has the
      presence of bacteriophages in the microbiome been highlighted, and their
      potential role in maintaining normal immunity has gained increasing attention. We
      summarize the available data pointing to the potential impact of phages in
      maintaining immunological homeostasis.

PMID- 28434235
TI  - Recirculation zone length in renal artery is affected by flow spirality and renal
      to-aorta flow ratio.
AB  - Haemodynamic perturbations such as flow recirculation zones play a key role in
      progression and development of renal artery stenosis, which typically originate
      at the aorta-renal bifurcation. The spiral nature of aortic blood flow, division
      of aortic blood flow in renal artery as well as the exercise conditions have been
      shown to alter the haemodynamics in both positive and negative ways. This study
      focuses on the combinative effects of spiral component of blood flow, renal-to
      aorta flow ratio and the exercise conditions on the size and distribution of
      recirculation zones in renal branches using computational fluid dynamics
      technique. Our findings show that the recirculation length was longest when the
      renal-to-aorta flow ratio was smallest. Spiral flow and exercise conditions were
      found to be effective in reducing the recirculation length in particular in small
      renal-to-aorta flow ratios. These results support the hypothesis that in renal
      arteries with small flow ratios where a stenosis is already developed an
      artificially induced spiral flow within the aorta may decelerate the progression
      of stenosis and thereby help preserve kidney function.

PMID- 28434236
TI  - Incremental Validity of Self- and Informant Report of Personality Disorders in
      Later Life.
AB  - Research shows moderate agreement between different sources of information when
      assessing personality disorders (PDs) in older adults. The differences between
      measurement methods appear to be not only the result of measurement error, but
      also an indication that each source holds nonredundant information relevant to PD
      diagnosis. The current article examines three sources of diagnostic information
      (self-report, informant report, and clinical interview) and the utility of these
      instruments in predicting important outcomes in older adulthood. We analyzed data
      from 1,630 adults between the ages of 55 and 64 years participating in a
      longitudinal study of later life. PD symptomatology was assessed using multiple
      methods, which were then used to predict health, marital satisfaction, and
      cognitive decline. All three sources contributed significantly to the prediction
      of these outcomes, with important implications for the assessment of older adults
      in research and clinical settings.

PMID- 28434237
TI  - Factor Structure and Invariance of an Adolescent Risks and Needs Assessment.
AB  - The Washington Assessment of Risks and Needs of Students is a youth self-report
      screening instrument developed for use by high school and juvenile court
      personnel faced with the legal and practical challenges of high truancy and
      dropout rates. It purports to measure six facets of risks and needs of youth
      relevant to improving school outcomes. In this study, a bifactor model measuring
      a general factor and six specific factors was examined for fit and invariance
      across different groups defined by sex and race/ethnicity, with a sample of court
      petitioned high school students ( N = 937; ages 13-17 years). The results of
      multigroup confirmatory factor analysis revealed an essentially invariant
      bifactor structure across the groups. Further analysis of reliability support the
      use of the general factor to guide decision making for youth at risk for truancy
      and school failure, and scores deriving from the six specific factors as
      providing insight on specific areas of risk and need.

PMID- 28434238
TI  - The Characteristics and Long-Term Course of Epilepsy in Lipoid Proteinosis: A
      Spectrum From Mild to Severe Seizures in Relation to ECM1 Mutations.
AB  - Lipoid proteinosis (LP) is a rare autosomal recessive disease characterized by
      deposition of hyaline material in skin and mucosae. Epilepsy, as an
      extracutaneous manifestation associated with typical mesial temporal
      calcifications, has already been identified, but its characteristics and long
      term prognosis have not been thoroughly investigated. We included 7 consecutive
      patients with LP with typical intracranial calcifications out of 16 patients with
      ECM1 mutations and investigated the semiologic features, ictal and interictal EEG
      findings, and long-term prognosis of epilepsy in this genodermatosis. Four of
      them had seizures (57.1%), and focal seizures with motionless staring were the
      most common seizure phenotype, originating from bilateral mesial temporal areas,
      but interictal spikes were scant. Auras were observed in three patients, mostly
      as epigastric sensation and deja vu, which indicated mesial temporal lobe origin.
      Three patients with homozygous mutations in sixth and seventh exons of the ECM1
      gene had a drug-resistant course at the end of long-term follow-up. Molecular
      genetic testing showed a rare compound heterozygous mutation in one patient,
      which was also associated with seizures but without drug-resistance. Our findings
      indicated a spectrum for epilepsy with a desperate drug-resistant course for
      decades in most patients with LP, which is still an underrecognized disease by
      neurologists.

PMID- 28434239
TI  - PCB-126 effects on aryl hydrocarbon receptor, ubiquitin and p53 expression levels
      in a fish product (Sparus aurata L.).
AB  - The aim of the present study is to determine if Ahr ligands as PCB-126, a dioxin
      like, might contribute to inhibition of the tumour suppressor p53 by promoting
      its degradation through proteasome-ubiquitin system (UPS). The findings show, in
      the presence of PCB-126, a significant increase in p53 immunoreactivity in fish
      compared to the control. Subsequently, there is a decrease in p53
      immunoreactivity at 24 h which is maintained even at 72 h. There is also a slight
      decrease in ubiquitin immunoreactivity to 12 h compared to the control and a
      marked decrease to 24 and 72 h. It's very important to underline as in this study
      we demonstrate a marked decrease in ubiquitin and p53 immunoreactivity at 24 and
      72 h. Our result emphasise the need to deeply the role of this receptor in UPS
      regulation as potential therapeutic target for cancer treatment.

PMID- 28434241
TI  - [Facilitating role of traumatic experiences in art].
AB  - Traumatic experiences can not only have unfavourable consequences, they can also
      contribute, with a kind of creative twist, to the development of the person
      affected by the trauma. The artistic responses to traumas can be examined on the
      basis of the different types of trauma. This study reports on an investigation
      focusing on six types of trauma: emotional deprivation/neglect; near-death
      experience; becoming the victim of violence; war; accident/sickness and emotional
      frustration. Examples taken from the history of art indicate that works of art
      can draw attention to the traumatic experiences of the artists with frequently
      repeated motifs and portrayal techniques (sun, mother image, objects referring to
      the person lost, motifs of violence or symbols of violence, artistic
      manifestations of an exaggerated self-image, surreal visions, dry irony,
      substituting other objects for the beloved person), or a sudden change of style
      and subject that can express a heightened interest in human suffering (Lovis
      Corinth). An emphasis placed on self-portrayal can indicate the artist's
      increased self-examination, in cases of sickness, or continuous monitoring of the
      state of mind (Frida Kahlo, Otto Dix, Lovis Corinth, Edvard Munch). In some cases
      artistic activity can help to work through the trauma (Hans Bellmer, Oskar
      Kokoschka, Max Ernst, Rene Magritte), in other cases it is not able to prevent
      the development of psychological/psychiatric consequences of the trauma
      (Artemisia Gentileschi, Edvard Munch, Lajos Gulacsy). Traumas can be the sources
      of motivation and provide themes for works of art; and, although not in all
      cases, artistic creativity can contribute to effectively working through
      traumatic experiences. Orv Hetil. 2017; 158(17): 668-677.

PMID- 28434242
TI  - [Hungarian Diet and Nutritional Status Survey - OTAP2014. III. Macroelement
      intake of the Hungarian population].
AB  - INTRODUCTION AND AIM: The Hungarian Diet and Nutritional Status Survey examined
      the dietary habits of the Hungarian adult population. The aim of the study is to
      present the macroelement intake of the population. METHOD: The study represents
      the macrolement intake of the population with age 18 or over on the day of 31
      December 2013, of those who are non-institutionalised. RESULTS: Salt intake
      decreased compared to the findings of the previous study in 2009 but it is still
      extremely high (15.9 g in men and 11.2 g in women). The potassium intake is below
      the recommendation, which together with a high sodium intake increases the risk
      of high blood pressure. Calcium intake in the youngest age group reached the
      recommendations, whereas the intake in the oldest age group was well below the
      references. Magnesium intake complied with the recommendation, the intake of
      phosphorus however exceeded it. High sodium intake still represents substantial
      public health risk. CONCLUSION: The reduction that occured in the population's
      salt intake since 2009 demonstrates the effectiveness of implemented prevention
      programs, cooperation with the industry and public awareness campaigns. Orv
      Hetil. 2017; 158(17): 653-661.

PMID- 28434243
TI  - [Clinical and neuropathological characteristics of dementia with Lewy bodies].
AB  - Dementia with Lewy bodies (DLB) is the second most common neurodegenerative
      dementia. The accurate diagnosis is often possible only by neuropathological
      examination. The morphologic hallmarks are the presence of alpha-synuclein-rich
      Lewy bodies and Lewy neurites, identical to those seen in Parkinson's disease
      (PD) and Parkinson's disease dementia (PDD). Neurotransmitter deficits, synaptic
      and ubiquitin-proteasome system (UPS) dysfunction play major role in the
      pathomechanism. Characteristic symptoms are cognitive fluctuation, parkinsonism
      and visual hallucinations. Due to the often atypical clinical presentation novel
      imaging techniques and biomarkers could help the early diagnosis. Although
      curative treatment is not available, therapies can improve quality of life.
      Clinicopathological studies are important in exploring pathomechanisms, ensuring
      accurate diagnosis and identifying therapeutic targets. Orv Hetil. 2017; 158(17):
      643-652.

PMID- 28434244
TI  - [Helping reintegration of patients suffering from chronic musculoskeletal
      diseases with decreased working ability in the National Institute of Rheumatology
      and Physiotherapy, Budapest, Hungary].
AB  - INTRODUCTION: An important task of our institute is to support social
      reintegration: including occupational rehabilitation of patients suffering from
      chronic musculoskeletal diseases with decreased working ability. AIM: The aim of
      the authors was to provide informations of their daily practice, how they perform
      patient education, giving information for their patients about their disease, the
      rehabilitation possibilities, how they support the patients with decreased
      working ability to take part in their own rehabilitation. METHOD: Patients taking
      part in in-patient rehabilitation received teaching and education about their
      disease and rehabilitation options in groups. Patients interested in part-time
      jobs were individually interviewed by a 30-120 minutes talk about their
      educational level and training, social conditions and about the available part
      time jobs. The part time jobs were available with the help of the Motivation
      Foundation of the National Association of the Societies of Motion Disabled, and
      the Alfa Rehabilitation Nonprofit Rt. The data of patients receiving in-patient
      rehabilitation betwen the 1st of January 2009 and 31st of December 2014 were
      analyzed. RESULTS: Out of the 230 patients seeking our help for part time job,
      our social service could organise jobs for 180 disabled persons, all town
      inhabitants, but was unsuccesful in getting jobs for patients living in villages
      and separated farms. CONCLUSION: Part time jobs can be organized for
      musculoskeletal disabled living in cities and towns. For village-dwellers there
      are no suitable jobs and working places. It is necessary to organize
      rehabilitation working possibitities for musculoskeletal disabled patients living
      in villages. Orv Hetil. 2017; 158(17): 662-667.

PMID- 28434245
TI  - Simultaneous quantitation of the BACE1 inhibitor AZD3293 and its metabolite
      AZ13569724 in human matrices by LC-MS/MS.
AB  - AIM: AZD3293 is a novel BACE1 inhibitor in Phase III development for Alzheimer's
      disease. Sensitive and robust bioanalytical methods were required to quantitate
      AZD3293 and its metabolite AZ13569724 in human biological matrices.
      METHODOLOGY/RESULTS: Human plasma was prepared by protein precipitation.
      Linearity for both analytes was in the range of 0.5-500 ng/ml with up to 100-fold
      dilution. Plasma ultrafiltrate samples were prepared using Centrifree(r)
      ultrafiltration device. Urine and CSF samples were analyzed directly after
      dilution. A 27% decrease in AZD3293 concentrations in the CSF collection apparati
      was found due to nonspecific binding. Incurred sample reanalysis was acceptable.
      CONCLUSION: Methods for simultaneous quantitation of AZD3293 and its metabolite
      AZ13569724 in human biological matrices have been validated and successfully
      applied to clinical studies.

PMID- 28434246
TI  - Sociodemographic Determinants of Low Fruit and Vegetable Consumption Among
      Bangladeshi Adults: Results From WHO-STEPS Survey 2010.
AB  - This study aimed to investigate factors affecting fruit and vegetables (FAVs)
      intake among Bangladeshi adults. Dietary data of 9275 adults from the Bangladesh
      Noncommunicable Disease Risk Factor Survey 2010 were analyzed. The mean age of
      the respondents was 42.4 (+/-13.5) years. Multistage cluster sampling was applied
      to identify samples. Demographics, personal habits, physical activity, diet, and
      anthropometric data were collected using the WHO-STEPs questionnaire. Average
      daily intake of <5 servings of FAVs combined was considered to be low FAV
      consumption, and its prevalence was 82.8%. A mixed-effect logistic regression
      model was fitted to assess association of factors with low FAV intake. Higher
      educational attainment, greater wealth, female sex, low physical activity, body
      mass index >25 kg/m2, and smokeless tobacco consumption were significantly
      associated with higher FAV consumption. Frequency of low FAV intake increased
      with increasing age and decreased with increasing educational attainment.
      Programs targeting people at risk of low FAV consumption are needed to promote
      consumption.

PMID- 28434247
TI  - Premature Mortality From Noncommunicable Diseases in the Federated States of
      Micronesia, 2003-2012.
AB  - This study was conducted to assess status, and understand burden, of premature
      and leading causes of deaths from noncommunicable diseases (NCDs) in the
      Federated States of Micronesia (FSM). From 2003 to 2012, ICD-10 coded mortality
      data from the national Health Information System were analyzed. Proportional
      mortality was calculated and a ranking list of the leading causes of premature
      death was produced. Of the 2349 premature deaths reported, 1970 (83.9%) were due
      to NCDs, and 1680 (71.5%) were from 4 main NCD groups-cardiovascular diseases,
      cancer, diabetes, and chronic respiratory diseases. Diabetes (19.5%), ischemic
      heart diseases (13.2%), and cerebrovascular diseases (7.1%) were the leading
      causes of premature deaths. The findings indicate that the burden of premature
      NCD deaths in FSM is higher than global levels, and existing efforts need to be
      strengthened to alter their course.

PMID- 28434248
TI  - Are University Students in Singapore Meeting the International and National
      Recommended Daily Servings of Fruits and Vegetables?
AB  - Data are lacking on fruit and vegetable (FV) consumption among young adults in
      the Asia-Pacific region. The aim of this study is to assess the prevalence of
      students who met the international and national recommendation of daily
      consumption of 5 and 4 FV servings, respectively, in a university in Singapore
      and the factors associated with meeting the national recommendation. A cross
      sectional survey using proportional stratified random sampling was conducted on
      884 undergraduates in 2013. The prevalence of meeting the international and
      national recommendation was 13.6% and 27.1%, respectively. The significant
      factors of meeting national recommendation were those from higher socioeconomic
      status, those making conscious effort to eat food high in fiber, those not
      skipping breakfast, those having a lower frequency of deep fried food consumption
      and those with higher meal frequency. Behavioral and structural interventions to
      educate, motivate and nudge university students to promote FV consumption are
      required in Singapore.

PMID- 28434249
TI  - Pulmonary Tuberculosis Is Associated With Biomass Fuel Use Among Rural Women in
      Pakistan: An Age- and Residence-Matched Case-Control Study.
AB  - Facility-based, age- and residential area-matched case-control study was
      conducted in Sindh, Pakistan to determine association between biomass fuel use
      for cooking and pulmonary tuberculosis (TB). Cases were women with pulmonary TB,
      and controls were those suffering from other diseases. Current users of biomass
      fuel were at higher risk of pulmonary TB (adjusted matched odds ratio [mOR] =
      3.0; 95% CI = 1.1-4.9) compared with nonusers. In comparison with former biomass
      users (women not using biomass for >10 years), recent biomass users (women who
      switched from biomass to nonbiomass <=10 years ago), and current (lifetime) users
      were at a higher risk in a dose-response manner (adjusted mOR = 2.8, 95% CI = 0.9
      8.2 and adjusted mOR = 3.9, 95% CI = 1.4-10.7, respectively). Population
      attributable fraction for TB related to biomass fuel use was 40.6% (95% CI =
      35.5%-45.7%). This study strengthens the evidence that biomass fuel use for
      cooking is associated with pulmonary TB and risk increases with duration of
      exposure.

PMID- 28434250
TI  - Rolling Tobacco in Banana Leaves, Newspaper, or Copybook Paper Associated With
      Significant Reduction in Lung Function in Vanuatu.
AB  - In addition to the widespread availability of packaged cigarettes, the
      inhabitants of island nations of the Southwest Pacific frequently smoke
      commercially available loose tobacco using manufactured rolling papers, as well
      as locally grown tobacco rolled in manufactured rolling paper or wrapped in
      leaves, copybook paper, and newspaper. In this study, Vanuatu men who smoked
      local tobacco rolled in leaves, copybook paper, or newspaper showed significantly
      lower forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1),
      and FEV1/FVC ratios than men who smoked packaged cigarettes, store-bought tobacco
      rolled in manufactured rolling paper, or who smoked locally grown tobacco rolled
      in manufactured rolling papers. The addition of toxins from these unusual tobacco
      wrapping media produces lung function deficits similar to the pattern noted among
      tobacco smokers who also inhale smoke from burning biomass. Thus, public health
      initiatives should consider including strategies addressing the use of wrapping
      media among smokers in South Pacific island societies.

PMID- 28434251
TI  - A Mock Randomized Controlled Trial With Audience Response Technology for Teaching
      and Learning Epidemiology.
AB  - The study's objective was to apply and assess an active learning approach to
      epidemiology and critical appraisal. Active learning comprised a mock, randomized
      controlled trial (RCT) conducted with learners in 3 countries. The mock trial
      consisted of blindly eating red Smarties candy (intervention) compared to yellow
      Smarties (control) to determine whether red Smarties increase happiness. Audience
      response devices were employed with the 3-fold purposes to produce outcome data
      for analysis of the effects of red Smarties, identify baseline and subsequent
      changes in participant's knowledge and confidence in understanding of RCTs, and
      assess the teaching approach. Of those attending, 82% (117 of 143 learners)
      participated in the trial component. Participating in the mock trial was a
      positive experience, and the use of the technology aided learning. The trial
      produced data that learners analyzed in "real time" during the class. The mock
      RCT is a fun and engaging approach to teaching RCTs and helping students to
      develop skills in critical appraisal.

PMID- 28434252
TI  - Vegetable Stir Fry and Fruit Salad: The Super Diet for Health.

PMID- 28434253
TI  - Risky Sexual Behaviors as Correlates of Depression and Suicidal Ideation Among
      Male HIV Test-Seekers at a Voluntary Counseling and Testing Facility in Taiwan.
AB  - This study aims at determining the level of depression and suicidal status of
      adult HIV test-seekers. Of the total enrolled 850 males, almost 50% reported some
      risk behaviors, 38.9% experienced depression, and 7.2% had suicidal ideation.
      Subjects with risky sexual behaviors in terms of repeated HIV test, had a history
      of sexually transmitted disease, engaged in one-night stands, or did not use
      condoms all the time with causal sexual partners were more likely to have
      depression. Furthermore, subjects who were bisexual/homosexual, engaged in
      Internet sex, engaged in one-night stands, or used addictive drugs within the
      past 6 months were more likely to experience suicidal ideation. The HIV testers
      are at risk of experiencing depression and suicidal ideation; each is associated
      with different types of risky sexual behaviors. It is essential for the health
      authority to further provide mental health services for HIV testers and to draw
      up an effective strategy in reducing unprotected sexual behaviors.

PMID- 28434254
TI  - Association of GSTT1 null, XPD 751 CC and XPC 939 CC genotypes with increased
      levels of genomic damage among hospital pathologists.
AB  - CONTEXT: Hospital workers are at risk for genotoxic damage following
      occupationally exposure to xenobiotics. Pathologists are exposed to chemicals
      during their use in health care environments, particularly throughout inhalation
      of airborne agents, absorption through skin or contact with the patient's body
      fluids. OBJECTIVE: We evaluated the level of genomic damage in a sample of 61
      hospital pathologists (occupationally exposed to antineoplastic drugs and
      sterilizing agents) and 60 control subjects. MATERIALS AND METHODS: Lymphocytes
      were analyzed by SCEs and CAs assays and genotyped for GSTT1, GSTM1, CYP1A1
      Ile/Val, XPD (A751C) and XPC (A939C) gene polymorphisms. RESULTS: Pathologists
      showed significantly higher frequencies of SCEs and CAs with respect to control
      subjects. GSTT1 null genotype was found to be associated with higher SCEs and CAs
      frequencies, whereas XPD 751 CC and XPC 939 CC genotypes only with a higher level
      of SCEs. DISCUSSION AND CONCLUSIONS: The SCEs and CAs results are consistent with
      other published data, placing hospital workers as a category at risk for
      genotoxic damage caused by chronic exposure to xenobiotics. The higher levels of
      cytogenetic damage observed among GSTT1 null, XPD 751 and XPC 939 CC homozygote
      subjects confirm the importance of the genetic polymorphisms analysis associated
      to genotoxicological studies.

PMID- 28434255
TI  - Daratumumab for the treatment of multiple myeloma.
AB  - INTRODUCTION: Proteasome inhibitors and immunomodulatory drugs have contributed
      to the dramatic improvement in survival for patients with myeloma over the past
      decades. However, the disease typically relapses and new classes of drugs are
      needed. In 2015, two monoclonal antibodies were approved for the treatment of
      patients with relapsed multiple myeloma, and immunotherapy has rapidly become
      indispensable in the management of myeloma patients. Areas covered: Here, the
      authors discuss the published data regarding the mechanism of action, safety and
      clinical efficacy of the CD38-targeted monoclonal antibody daratumumab for the
      treatment of patients with multiple myeloma. Expert opinion: Daratumumab is
      indicated for myeloma patients who have received at least 3 prior therapies,
      including bortezomib, lenalidomide and pomalidomide. In 2016, daratumumab in
      combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone
      was approved for the treatment of patients with multiple myeloma who have
      received at least one prior therapy. Daratumumab displays an excellent safety
      profile. Moderate-grade infusion-related reactions occurring mostly during the
      first infusion are the main treatment-emergent adverse event. In the context of
      daratumumab therapy, attention should be paid to interference with blood
      compatibility testing and response assessment. Daratumumab-based combination
      therapies are currently under evaluation in relapsed and newly diagnosed
      patients.

PMID- 28434256
TI  - A bioinformatics roadmap for the human vaccines project.
AB  - Biomedical research has become a data intensive science in which high throughput
      experimentation is producing comprehensive data about biological systems at an
      ever-increasing pace. The Human Vaccines Project is a new public-private
      partnership, with the goal of accelerating development of improved vaccines and
      immunotherapies for global infectious diseases and cancers by decoding the human
      immune system. To achieve its mission, the Project is developing a Bioinformatics
      Hub as an open-source, multidisciplinary effort with the overarching goal of
      providing an enabling infrastructure to support the data processing, analysis and
      knowledge extraction procedures required to translate high throughput, high
      complexity human immunology research data into biomedical knowledge, to determine
      the core principles driving specific and durable protective immune responses.

PMID- 28434257
TI  - Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N
      oxide in non-diabetic subjects.
AB  - Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from
      phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further
      converted to trimethylamine-N-oxide (TMAO), which could play a role in
      cardiometabolic disease. Red meat-derived products are one of the major
      environmental sources of advanced glycation end products (AGEs) that may also
      contribute to the pathogenesis of cardiometabolic disorders through the
      interaction with receptor for AGEs (RAGE). However, the relationship among AGEs,
      soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic
      subjects underwent a physical examination, determination of blood chemistry and
      anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple
      regression analyses revealed that HbA1c, uric acid and AGEs were independently
      associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were
      independently correlated with log TMAO. Our present findings indicated that AGEs
      to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic
      disorders.

PMID- 28434258
TI  - Protective effects of casein-derived peptide VLPVPQK against hydrogen peroxide
      induced dysfunction and cellular oxidative damage in rat osteoblastic cells.
AB  - Oxidative stress inhibits osteoblast differentiation and function that lead to
      the development of osteoporosis. Casein-derived peptide VLPVPQK (PEP), a potent
      antioxidant, was isolated from beta-casein of buffalo milk. We used an in vitro
      oxidative stress model induced by hydrogen peroxide (H2O2) in rat osteoblastic
      cells to investigate the protective effects of PEP against H2O2-induced
      dysfunction and oxidative damage. Cells were pretreated with PEP (50-200 ng/mL)
      for 2, 7 or 21 days followed by 0.3 mM H2O2 treatment for 24 h and then markers
      of osteogenic development, oxidative damage and apoptosis were examined. PEP
      significantly increased the viability and differentiation markers of osteoblast
      cells such as alkaline phosphatase and calcium mineralization. Moreover, PEP
      suppressed the production of reactive oxygen species (ROS), lipid peroxidation
      and ameliorated H2O2-induced reduction in glutathione, superoxide dismutase and
      catalase activities. In addition, PEP partially inhibited caspase-9 and-3
      activities and reduced propidium iodide-positive cells. Altogether, our results
      demonstrated that PEP could protect rat osteoblast against H2O2-induced
      dysfunction and oxidative damage by reduction of ROS production, lipid
      peroxidation and increased antioxidant enzyme activities. Thus, our data suggest
      that PEP might be a valuable protective agent against oxidative stress-related
      diseases such as osteoporosis.

PMID- 28434259
TI  - Establishing and validating the fluorescent amyloid ligand h-FTAA (heptamer
      formyl thiophene acetic acid) to identify transthyretin amyloid deposits in
      carpal tunnel syndrome.
AB  - Transthyretin-derived (ATTR) amyloidosis is a frequent finding in carpal tunnel
      syndrome. We tested the following hypotheses: the novel fluorescent amyloid
      ligand heptameric formic thiophene acetic acid (h-FTAA) has a superior
      sensitivity for the detection of amyloid compared with Congo red-staining;
      Amyloid load correlates with patient gender and/or patient age. We retrieved 208
      resection specimens obtained from 184 patients with ATTR amyloid in the carpal
      tunnel. Serial sections were stained with Congo red, h-FTAA and an antibody
      directed against transthyretin (TTR). Stained sections were digitalized and
      forwarded to computational analyses. The amount of amyloid was correlated with
      patient demographics. Amyloid stained intensely with h-FTAA and an anti-TTR
      antibody. Congo red-staining combined with fluorescence microscopy was
      significantly less sensitive than h-FTAA-fluorescence and TTR-immunostaining: the
      highest percentage area was found in TTR-immunostained sections, followed by h
      FTAA and Congo red. The Pearson correlation coefficient was .8 (Congo red vs. h
      FTAA) and .9 (TTR vs. h-FTAA). Amyloid load correlated with patient gender,
      anatomical site and patient age. h-FTAA is a highly sensitive method to detect
      even small amounts of ATTR amyloid in the carpal tunnel. The staining protocol is
      easy and h-FTAA may be a much more sensitive procedure to detect amyloid at an
      earlier stage.

PMID- 28434260
TI  - Dapsone-associated fixed drug eruption.
AB  - INTRODUCTION: Dapsone is a sulfone drug used to treat infectious conditions and
      also numerous dermatologic diseases. Fixed drug eruption is a distinctive adverse
      cutaneous reaction associated with the initial administration and subsequent
      delivery of a specific agent. Areas covered: The authors preformed a literature
      search using the following keywords: dapsone, fixed drug eruption, and adverse
      cutaneous drug reaction. Bibliographies were also reviewed for pertinent
      articles. The results were combed for relevant papers and reviewed. Articles
      pertaining to dapsone-associated fixed drug eruption were included. Expert
      commentary: The majority of cases of dapsone-associated fixed drug eruption in
      the literature come from Africa or India where there is a high prevalence of
      patients treated for leprosy. Characteristics of these cases are similar to fixed
      drug eruption described in the western literature, with differences in frequency
      of multiple versus solitary lesions. Dapsone-associated fixed drug eruption
      should be considered when reviewing the drug history of a patient with fixed drug
      eruption. In the case of darker pigmented individuals, multiple fixed drug
      eruption lesions may be more common. Multiple lesions may mimic Kaposi's sarcoma
      in human immunodeficiency virus positive patients. Dapsone-associated fixed drug
      eruption should be considered in the differential diagnosis of multiple
      hyperpigmented lesions.

PMID- 28434261
TI  - Strategies to prevent infections associated with cardiovascular implantable
      electronic devices.
AB  - INTRODUCTION: Infections involving cardiovascular implantable electronic devices
      (CIED) are associated with high morbidity and mortality and substantial financial
      cost. In the past two decades, the rate of CIED infections has increased
      disproportionate to the number of devices implanted, likely due to aging patient
      population with multiple comorbidities. Microbial contamination of the generator
      pocket and or leads by skin flora at the time of implantation is a major
      mechanism for early CIED infections. Due to resistance to host immune cells and
      antibiotics caused by biofilm formation, complete removal of the device generator
      and leads is required to achieve cure. Areas covered: In this manuscript, we
      review the published literature regarding epidemiology, risk factors, and
      pathogenesis of CIED infections with primary focus on the preventative strategies
      to reduce the incidence of device infections. Expert commentary: Strict adherence
      to infection control measures at the time of CIED implantation is critical in
      reducing the risk of device infection while adjunctive strategies such as use of
      antimicrobial envelopes might help in certain high-risk individuals.
      Technological advances in device manufacturing with availability of subcutaneous
      devices without transvenous leads and self-contained intracardiac devices without
      leads and generator show promise with lower risk of infection.

PMID- 28434262
TI  - The emergence of acid ceramidase as a therapeutic target for acute myeloid
      leukemia.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) is the most common adult leukemia.
      Only a fraction of AML patients will survive with existing chemotherapy regimens.
      Hence, there is an urgent and unmet need to identify novel targets and develop
      better therapeutics in AML. In the past decade, the field of sphingolipid
      metabolism has emerged into the forefront of cancer biology due to its importance
      in cancer cell proliferation and survival. In particular, acid ceramidase (AC)
      has emerged as a promising therapeutic target due to its role in neutralizing the
      pro-death effects of ceramide. Areas covered: This review highlights key
      information about AML biology as well as current knowledge on dysregulated
      sphingolipid metabolism in cancer and AML. We describe AC function and
      dysregulation in cancer, followed by a review of studies that report elevated AC
      in AML and compounds known to inhibit the enzyme. Expert opinion: AML has a great
      need for new drug targets and better therapeutic agents. The finding of elevated
      AC in AML supports the concept that this enzyme represents a novel and realistic
      therapeutic target for this common leukemia. More effort is needed towards
      developing better AC inhibitors for clinical use and combination treatment with
      existing AML therapies.

PMID- 28434265
TI  - Adipose tissue infiltration in minor salivary glands of patients with Sjogren's
      syndrome: Lack of significant correlation with the disease. An image analysis of
      174 cases.
AB  - Fatty infiltration in minor salivary gland biopsies and its correlation to
      systemic autoimmune diseases are controversial in the literature. Presence and
      extent of fatty infiltration in minor salivary glands of 107 Sjogren's syndrome
      patients and 67 age-matched sicca controls were compared with statistical
      analyses. No significant difference was found regarding the presence or the
      extent of fatty infiltration between the two groups. Fatty infiltration seems to
      be unrelated to Sjogren's syndrome thus its examination in salivary gland biopsy
      samples cannot improve the diagnostic accuracy of the disease.

PMID- 28434264
TI  - Exploring effects of remote ischemic preconditioning in a pig model of
      hypothermic circulatory arrest.
AB  - OBJECTIVES: During aortic and cardiac surgery, risks for mortality and morbidity
      are inevitable. Surgical setups involving deep hypothermic circulatory arrest
      (DHCA) are effective to achieve organ protection against ischemic injury. The aim
      of this study was to identify humoural factors mediating additive protective
      effects of remote ischemic preconditioning (RIPC) in a porcine model of DHCA.
      DESIGN: Twenty-two pigs were randomized into the RIPC group (n = 11) and the
      control group (n = 11). The RIPC group underwent four 5-minute hind limb ischemia
      reperfusion cycles prior to cardiopulmonary bypass and DHCA. All animals
      underwent identical surgical procedures including 60 min DHCA at 18  degrees C.
      Blood samples were collected from vena cava and sagittal sinus at several time
      points. After the 8-hour follow-up period, the brain, heart, and kidney tissue
      samples were collected for tissue analyses. RESULTS: Serum levels of brain damage
      marker S100B recovered faster in the RIPC group, after 4 hours of the arrest, (p
      < .05). Systemic lactate levels were lower and cardiac index was higher in the
      RIPC group postoperatively. Immunohistochemical cerebellum regional scores of
      antioxidant response regulator Nrf2 were better in the RIPC group (mean: 1.1,
      IQR: 0.0-2.5) compared with the control group (mean: 0.0, IQR: 0.0-0.0), reaching
      borderline statistical significance (p = .064). RIPC induced detectable
      modulations of plasma proteome and metabolites. CONCLUSIONS: The faster recovery
      of S100B, lower systemic lactate levels and favourable regional antioxidant
      response suggest possible neuronal cellular and mitochondrial protection by RIPC,
      whereas better cardiac index underlines functional effects of RIPC. The exact
      humoural factor remains unclear.

PMID- 28434266
TI  - Factors associated with the efficacy of miniprobe endoscopic ultrasonography
      after conventional endoscopy for the prediction of invasion depth of early
      gastric cancer.
AB  - BACKGROUND: This study aimed to compare the accuracy of conventional endoscopy
      (CE) and endoscopic ultrasonography (EUS) to predict tumor invasion depth and to
      determine factors associated with higher accuracy of additional miniprobe EUS
      after CE. METHODS: Between May 2009 and February 2015, 273 lesions in 266
      patients were subjected to miniprobe EUS after CE and curative treatment for well
      to-moderately differentiated early gastric cancer (EGC). We reviewed preoperative
      CE and EUS findings and compared them to the pathologic findings. RESULTS: The
      accuracy of CE and EUS to estimate the invasion depth of EGCs was 78.8% (215/273)
      and 83.9% (229/273) (p = .124), respectively. Using multivariate analysis,
      irregular depressed surface (odds ratio [OR] 8.11; 95% confidence interval [CI]:
      2.79-23.53), fold change (OR 7.22; 95% CI: 2.33-22.38), size >2 cm (OR 2.72; 95%
      CI: 1.15-6.42) and ulcer scar (OR 2.64; 95% CI: 1.07-6.49) were associated with
      the higher accuracy of EUS than that of CE. CONCLUSIONS: Routine assessment using
      miniprobe EUS did not increase the accuracy of predicting invasion depth,
      compared to CE. However, EUS could be helpful in the treatment decision-making
      process for EGCs with lesions having irregular surfaces, fold change, size >2 cm,
      or ulcer scar.

PMID- 28434263
TI  - Plant protein-based hydrophobic fine and ultrafine carrier particles in drug
      delivery systems.
AB  - For thousands of years, plants and their products have been used as the mainstay
      of medicinal therapy. In recent years, besides attempts to isolate the active
      ingredients of medicinal plants, other new applications of plant products, such
      as their use to prepare drug delivery vehicles, have been discovered.
      Nanobiotechnology is a branch of pharmacology that can provide new approaches for
      drug delivery by the preparation of biocompatible carrier nanoparticles (NPs). In
      this article, we review recent studies with four important plant proteins that
      have been used as carriers for targeted delivery of drugs and genes. Zein is a
      water-insoluble protein from maize; Gliadin is a 70% alcohol-soluble protein from
      wheat and corn; legumin is a casein-like protein from leguminous seeds such as
      peas; lectins are glycoproteins naturally occurring in many plants that recognize
      specific carbohydrate residues. NPs formed from these proteins show good
      biocompatibility, possess the ability to enhance solubility, and provide
      sustained release of drugs and reduce their toxicity and side effects. The
      effects of preparation methods on the size and loading capacity of these NPs are
      also described in this review.

PMID- 28434267
TI  - Amyloid in bone marrow smears in systemic light-chain amyloidosis.
AB  - We performed a prospective sensitivity analysis to detect amyloid in bone marrow
      (BM) smears stained with Congo red (CR) and according to Pappenheim of patients
      with systemic light-chain (AL) amyloidosis. Results were directly compared to
      routine BM histology and fat aspiration. We analysed 198 BM smears from patients
      with the diagnosis or suspicion of systemic AL amyloidosis. Ultimately, the
      diagnosis could be established for 168 patients. Amyloid was detected on BM
      smears with CR in 33% (56/168). All patients suspicious for amyloid on Pappenheim
      staining (n = 39) showed substantial amyloid infiltration on CR. No patient
      without systemic AL amyloidosis stained positive. Sensitivity for routine BM
      histology was 57% (74/129) and for fat aspiration 96% (134/140). Patients with
      amyloid on BM smears had significantly more hepatic (42 vs. 9%, p < .001), renal
      (78 vs. 43%, p < .001) and gastrointestinal involvement (40 vs. 22%, p < .01) and
      less commonly cardiac involvement (58 vs. 76%, p < .03) and consecutively no
      adverse prognosis. CR staining of BM smears cannot be recommended as a primary
      screening tool for systemic AL as its overall sensitivity is far inferior to BM
      histology and fat aspiration. However, we recommend using the technique when
      suspecting amyloid on Pappenheim staining to establish the diagnosis of systemic
      AL amyloidosis.

PMID- 28434268
TI  - Ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a therapeutic and diagnostic target
      in neurodegeneration, neurotrauma and neuro-injuries.
AB  - INTRODUCTION: Since its discovery as a major CNS-abundant protein 25 years ago,
      Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in
      regulating brain protein metabolism, by coupling to the proteasome pathway of
      protein degradation. Areas covered: UCH-L1 is implicated in both familial and
      sporadic Parkinson disease and other chronic neurodegenerative diseases. Also,
      UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms
      of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity
      coupled with the gain of proteinopathy function are linked to neurodegeneration
      such as Parkinsonism and Alzheimer's disease. In addition, certain post
      translational modifications of UCH-L1 might promote the conversion of the
      cytosolic UCH-L1(C) to the membrane-associated UCH-L1(M) form, which seems to
      play a role in alpha-synucleinopathy formation. Thus, targeting the conversion of
      UCH-L1(C) to the UCH-L1(M) form might be the key to developing therapies for
      neurodegenerative diseases linked to UCH-L1. In parallel, UCH-L1 is also emerging
      as a promising neuron-derived biomarker for traumatic brain injury, ischemic and
      homographic stroke, pediatric hypoxic-ischemic encephalopathy, spinal cord
      injury, epileptic seizure and cardiac arrest. This shows that UCH-L1 has strong
      potential as a robust and universal biomarker target for various forms of CNS
      injury.

PMID- 28434269
TI  - Electronic adherence monitoring device performance and patient acceptability: a
      randomized control trial.
AB  - BACKGROUND: To investigate the performance and patient acceptability of an
      inhaler electronic monitoring device in a real-world childhood asthma population.
      METHODS: Children 6 to 15 years presenting with asthma to the hospital emergency
      department and prescribed inhaled corticosteroids were included. Participants
      were randomized to receive a device with reminder features enabled or disabled
      for use with their preventer. Device quality control tests were conducted.
      Questionnaires on device acceptability, utility and ergonomics were completed at
      six months. RESULTS: A total of 1306 quality control tests were conducted; 84%
      passed pre-issue and 87% return testing. The most common failure reason was
      actuation under-recording. Acceptability scores were high, with higher scores in
      the reminder than non-reminder group (median, 5th-95th percentile: 4.1, 3.1-5.0
      versus 3.7, 2.3-4.8; p < 0.001). Most (>90%) rated the device easy to use.
      Feedback was positive across five themes: device acceptability, ringtone
      acceptability, suggestions for improvement, effect on medication use, and effect
      on asthma control. CONCLUSIONS: This study investigates electronic monitoring
      device performance and acceptability in children using quantitative and
      qualitative measures. Results indicate satisfactory reliability, although failure
      rates of 13-16% indicate the importance of quality control. Favorable
      acceptability ratings support the use of these devices in children.

PMID- 28434270
TI  - What is stable pain control? A prospective longitudinal study to assess the
      clinical value of a personalized pain goal.
AB  - BACKGROUND: A universal consensus regarding standardized pain outcomes does not
      exist. The personalized pain goal has been suggested as a clinically relevant
      outcome measure. AIM: To assess the feasibility of obtaining a personalized pain
      goal and to compare a clinically based personalized pain goal definition versus a
      research-based study definition for stable pain. DESIGN: Prospective longitudinal
      descriptive study. MEASURES: The attending physician completed routine
      assessments, including a personalized pain goal and the Edmonton Classification
      System for Cancer Pain, and followed patients daily until stable pain control,
      death, or discharge. Stable pain for cognitively intact patients was defined as
      pain intensity less than or equal to desired pain intensity goal (personalized
      pain goal definition) or pain intensity ?3 (Edmonton Classification System for
      Cancer Pain study definition) for three consecutive days with <3 breakthroughs
      per day. SETTING/PARTICIPANTS: A total of 300 consecutive advanced cancer
      patients were recruited from two acute care hospitals and a tertiary palliative
      care unit. RESULTS: In all, 231/300 patients (77%) had a pain syndrome; 169/231
      (73%) provided a personalized pain goal, with 113/169 (67%) reporting a
      personalized pain goal ?3 (median = 3, range = 0-10). Using the personalized pain
      goal definition as the gold standard, sensitivity and specificity of the Edmonton
      Classification System for Cancer Pain definition were 71.3% and 98.5%,
      respectively. For mild (0-3), moderate (4-6), and severe (7-10) pain, the highest
      sensitivity was for moderate pain (90.5%), with high specificity across all three
      categories (95%-100%). CONCLUSION: The personalized pain goal is a feasible
      outcome measure for cognitively intact patients. The Edmonton Classification
      System for Cancer Pain definition closely resembles patient-reported personalized
      pain goals for stable pain and would be appropriate for research purposes. For
      clinical pain management, it would be important to include the personalized pain
      goal as standard practice.

PMID- 28434271
TI  - Minimizing atelectasis formation during general anaesthesia-oxygen washout is a
      non-essential supplement to PEEP.
AB  - BACKGROUND: Following preoxygenation and induction of anaesthesia, most patients
      develop atelectasis. We hypothesized that an immediate restoration to a low
      oxygen level in the alveoli would prevent atelectasis formation and improve
      oxygenation during the ensuing anaesthesia. METHODS: We randomly assigned 24
      patients to either a control group (n = 12) or an intervention group (n = 12)
      receiving an oxygen washout procedure directly after intubation. Both groups
      were, depending on body mass index, ventilated with a positive end-expiratory
      pressure (PEEP) of 6-8 cmH2O during surgery. The atelectasis area was studied by
      computed tomography before emergence. Oxygenation levels were evaluated by
      measuring blood gases and calculating estimated venous admixture (EVA). RESULTS:
      The atelectasis areas expressed as percentages of the total lung area were 2.0
      (1.5-2.7) (median [interquartile range]) and 1.8 (1.4-3.3) in the intervention
      and control groups, respectively. The difference was non-significant, and also
      oxygenation was similar between the two groups. Compared to oxygenation before
      the start of anaesthesia, oxygenation at the end of surgery was improved in the
      intervention group, mean (SD) EVA from 7.6% (6.6%) to 3.9% (2.9%) (P = .019) and
      preserved in the control group, mean (SD) EVA from 5.0% (5.3%) to 5.6% (7.1%) (P
      = .59). CONCLUSION: Although the oxygen washout restored a low pulmonary oxygen
      level within minutes, it did not further reduce atelectasis size. Both study
      groups had small atelectasis and good oxygenation. These results suggest that a
      moderate PEEP alone is sufficient to minimize atelectasis and maintain
      oxygenation in healthy patients.

PMID- 28434272
TI  - Wideband acoustic immittance in children with Down syndrome: prediction of middle
      ear dysfunction, conductive hearing loss and patent PE tubes.
AB  - OBJECTIVE: The purpose of this study was to evaluate pressurised wideband
      acoustic immittance (WAI) tests in children with Down syndrome (DS) and in
      typically developing children (TD) for prediction of conductive hearing loss
      (CHL) and patency of pressure equalising tubes (PETs). DESIGN: Audiologic
      diagnosis was determined by audiometry in combination with distortion-product
      otoacoustic emissions, 0.226 kHz tympanometry and otoscopy. WAI results were
      compared for ears within diagnostic categories (Normal, CHL and PET) and between
      groups (TD and DS). STUDY SAMPLE: Children with DS (n = 40; mean age 6.4 years),
      and TD children (n = 48; mean age 5.1 years) were included. RESULTS: Wideband
      absorbance was significantly lower at 1-4 kHz in ears with CHL compared to NH for
      both TD and DS groups. In ears with patent PETs, wideband absorbance and group
      delay (GD) were larger than in ears without PETs between 0.25 and 1.5 kHz.
      Wideband absorbance tests were performed similarly for prediction of CHL and
      patent PETs in TD and DS groups. CONCLUSIONS: Wideband absorbance and GD revealed
      specific patterns in both TD children and those with DS that can assist in
      detection of the presence of significant CHL, assess the patency of PETs, and
      provide frequency-specific information in the audiometric range.

PMID- 28434273
TI  - Development of Distinct Body Mass Index Trajectories Among Children Before Age 5
      Years: A Population-Based Study.
AB  - The prevalence of childhood obesity has increased over the past 3 decades. This
      study was designed to understand how childhood body mass index (BMI) influences
      later risk of obesity. We calculated BMIs for children residing in Olmsted
      County, Minnesota, between January 1, 2005 and December 31, 2012 using medical
      records data. We defined homogenous BMI trajectory clusters using a nonparametric
      hill-climbing algorithm. Overall, 16,538 (47%) children had >3 weight assessments
      at least 1 year apart and were included in the analyses. Within the 8-year follow
      up period, children who were younger than 2 years and overweight had a 3- fold
      increase of obesity (adjusted hazard ratio [HR] = 3.24; 95% confidence interval
      [CI] = 2.69-3.89) and those aged 5 years and overweight had a 10-fold increased
      risk of obesity (adjusted HR = 9.97, 95% CI = 8.55-11.62). Three distinct BMI
      trajectories could be distinguished prior to 5 years of age. The risk of
      developing obesity in those who are overweight increased dramatically with
      increasing age. Interventions to prevent obesity need to occur prior to school
      age to prevent children from entering unhealthy BMI trajectories.

PMID- 28434274
TI  - Myoinositol combined with alpha-lipoic acid may improve the clinical and
      endocrine features of polycystic ovary syndrome through an insulin-independent
      action.
AB  - The aim of our study was to investigate the effects of a combined treatment with
      alpha-lipoic acid (ALA) and myoinositol (MYO) on clinical, endocrine and
      metabolic features of women affected by polycystic ovary syndrome (PCOS). In this
      pilot cohort study, forty women with PCOS were enrolled and clinical, hormonal
      and metabolic parameters were evaluated before and after a six-months combined
      treatment with ALA and MYO daily. Studied patients experienced a significant
      increase in the number of cycles in six months (p < 0.01). The free androgen
      index (FAI), the mean androstenedione and DHEAS levels significantly decreased
      after treatment (p < 0.05). Mean SHBG levels significantly raised (p < 0.01). A
      significant improvement in mean Ferriman-Gallwey (F-G) score (p < 0.01) and a
      significant reduction of BMI (p < 0.01) were also observed. A significant
      reduction of AMH levels, ovarian volume and total antral follicular count were
      observed in our studied women (p< 0.05). No significant changes occurred in gluco
      insulinaemic and lipid parameters after treatment. The combined treatment of ALA
      and MYO is able to restore the menstrual pattern and to improve the hormonal
      milieu of PCOS women, even in the absence of apparent changes in insulin
      metabolism.

PMID- 28434275
TI  - Cost-effectiveness of a transitional home-based palliative care program for
      patients with end-stage heart failure.
AB  - BACKGROUND: Studies have shown positive clinical outcomes of specialist
      palliative care for end-stage heart failure patients, but cost-effectiveness
      evaluation is lacking. AIM: To examine the cost-effectiveness of a transitional
      home-based palliative care program for patients with end-stage heart failure
      patients as compared to the customary palliative care service. DESIGN: A cost
      effectiveness analysis was conducted alongside a randomized controlled trial
      (Trial number: NCT02086305). The costs included pre-program training,
      intervention, and hospital use. Quality of life was measured using SF-6D.
      SETTING/PARTICIPANTS: The study took place in three hospitals in Hong Kong. The
      inclusion criteria were meeting clinical indicators for end-stage heart failure
      patients including clinician-judged last year of life, discharged to home within
      the service area, and palliative care referral accepted. A total of 84 subjects
      (study = 43, control = 41) were recruited. RESULTS: When the study group was
      compared to the control group, the net incremental quality-adjusted life years
      gain was 0.0012 (28 days)/0.0077 (84 days) and the net incremental costs per case
      was -HK$7935 (28 days)/-HK$26,084 (84 days). The probability of being cost
      effective was 85% (28 days)/100% (84 days) based on the cost-effectiveness
      thresholds recommended both by National Institute for Health and Clinical
      Excellence (L20,000/quality-adjusted life years) and World Health Organization
      (Hong Kong gross domestic product/capita in 2015, HK$328117). CONCLUSION: Results
      suggest that a transitional home-based palliative care program is more cost
      effective than customary palliative care service. Limitations of the study
      include small sample size, study confined to one city, clinic consultation costs,
      and societal costs including patient costs and unpaid care-giving costs were not
      included.

PMID- 28434276
TI  - Exposure to mobile phone (900-1800 MHz) during pregnancy: tissue oxidative stress
      after childbirth.
AB  - BACKGROUND: The present study has investigated the effects of mobile phone (900
      1800 MHz)-induced electromagnetic radiation on redox status in the heart, liver,
      kidney, cerebellum, and hippocampus of dams and the offspring mice. MATERIALS AND
      METHODS: Pregnant Balb/C were divided into two groups including the control and
      the experimental group. The experimental group was exposed to mobile phone (900
      1800 MHz), during pregnancy (2 h/d for 20 d). The dams and the offspring of both
      groups were sacrificed and tissues of interest were harvested immediately after
      delivery. Malondialdehyde (MDA) concentration, total thiol groups (TTG) content,
      superoxide dismutase (SOD), and catalase (CAT) activities were determined in the
      tissues. RESULTS: In the experimental groups, MDA levels were significantly
      increased, while TTG, SOD, and CAT were significantly decreased in the total
      tissues of dams and their offspring. CONCLUSION: Exposure to mobile phone (900
      1800 MHz) during pregnancy induced oxidative stress in tissues of dams and their
      offspring.

PMID- 28434277
TI  - Patients are doing it for themselves: A survey on disease-specific knowledge
      acquisition among people with Parkinson's disease in Sweden.
AB  - Effective self-management is key to living well with Parkinson's disease and one
      important aspect is disease-specific knowledge. This article explores how people
      with Parkinson's disease in Sweden (1) acquire disease-specific knowledge and (2)
      use Parkinson's disease-related healthcare. Data were collected through an online
      survey, which had 346 respondents (16-87 years old, median age: 68 years, 51%
      male; time since diagnosis: 0-31 years, median time: 7 years). Our results show
      that disease-specific knowledge is mainly found online, especially for women with
      Parkinson's disease and people with Parkinson's disease of working age, that most
      people with Parkinson's disease in Sweden see their neurologist for 1 h or less
      per year and only one in two people with Parkinson's disease has regular contact
      with other Parkinson's disease-related healthcare professionals. We also find
      that people with Parkinson's disease reporting higher levels of specific
      knowledge also are more likely to be satisfied with the amount of time they get
      with their neurologist, regardless of the amount of time.

PMID- 28434278
TI  - Electronic health record use among cancer patients: Insights from the Health
      Information National Trends Survey.
AB  - Over 90% of US hospitals provide patients with access to e-copy of their health
      records, but the utilization of electronic health records by the US consumers
      remains low. Guided by the comprehensive information-seeking model, this study
      used data from the National Cancer Institute's Health Information National Trends
      Survey 4 (Cycle 4) and examined the factors that explain the level of electronic
      health record use by cancer patients. Consistent with the model, individual
      information-seeking factors and perceptions of security and utility were
      associated with the frequency of electronic health record access. Specifically,
      higher income, prior online information seeking, interest in accessing health
      information online, and normative beliefs were predictive of electronic health
      record access. Conversely, poorer general health status and lack of health care
      provider encouragement to use electronic health records were associated with
      lower utilization rates. The current findings provide theory-based evidence that
      contributes to the understanding of the explanatory factors of electronic health
      record use and suggest future directions for research and practice.

PMID- 28434279
TI  - Extended use of electronic health records by primary care physicians: Does the
      electronic health record artefact matter?
AB  - The deployment of electronic health record systems is deemed to play a decisive
      role in the transformations currently being implemented in primary care medical
      practices. This study aims to characterize electronic health record systems from
      the perspective of family physicians. To achieve this goal, we conducted a survey
      of physicians practising in private clinics located in Quebec, Canada. We used
      valid responses from 331 respondents who were found to be representative of the
      larger population. Data provided by the physicians using the top three electronic
      health record software products were analysed in order to obtain statistically
      adequate sub-sample sizes. Significant differences were observed among the three
      products with regard to their functional capability. The extent to which each of
      the electronic health record functionalities are used by physicians also varied
      significantly. Our results confirm that the electronic health record artefact
      'does matter', its clinical functionalities explaining why certain physicians
      make more extended use of their system than others.

PMID- 28434281
TI  - Crosstalk Between Human Monocytic U937 Cells and Gingival Fibroblasts in
      Coculturally Enhanced Matrix Metalloproteinase-2 Expression.

PMID- 28434280
TI  - Use of a custom-made limb-press model to assess intra- and extracapsular
      techniques for treating cranial cruciate ligament rupture in cats.
AB  - Objectives This study aimed to compare the under-and-over technique, a type of
      intracapsular treatment, and the standard fabella-tibial suture, a method for
      extracapsular treatment, in achieving immediate, postoperative stifle stability
      after cranial cruciate ligament (CrCL) rupture by using a feline, custom-made
      limb-press model. Methods Cadaveric feline hindlimb specimens (n = 14) were
      positioned in the limb press at predefined joint angles (stifle joint: 120
      degrees ; hock joint: 120 degrees ), and vertical loads of 5%, 10%, 20% and 30%
      body weight were applied statically. Mediolateral radiographic views were
      obtained of the stifles under each load before and after CrCL transection, as
      well as after treatment with either of the two surgical techniques, and
      differences in distance between two predefined radiographic points for each
      radiograph were analysed. Results The general linear model showed a significant
      effect of load ( P <0.01) and technique ( P = 0.004) and a significant
      interaction between load and technique ( P = 0.006) regarding craniocaudal stifle
      stability. Distances between predefined tibial and femoral reference points were
      consistently higher in transected CrCLs than in intact stifles. All standard
      fabella-tibial suture-treated stifles (n = 7) were stable at all loads tested. Of
      the seven under-and-over technique-treated stifles, one was unstable at 20% body
      weight load and three at 30% body weight load. Conclusions and relevance Our
      model, which appropriately reproduced certain aspects of domestic shorthair cat
      stifle mechanics, indicated that a 40 lb monofilament nylon prosthesis, tightened
      at 20 N, produces more favourable biomechanical stabilisation of craniocaudal
      cruciate-related stifle instability than a 0.5 cm wide strip of fascia lata
      applied intracapsularly.

PMID- 28434282
TI  - Macrophages Play a Key Role in the Obesity-Induced Periodontal Innate Immune
      Dysfunction via Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3
      Pathway.

PMID- 28434283
TI  - Considering tapentadol as a first-line analgesic: 14 questions.
AB  - Tapentadol is the newest centrally acting analgesic to be approved by the US FDA
      and regulatory bodies in other countries. It has been called the first-in-class
      of a novel-acting analgesic mechanism of action that combines u-opioid receptor
      agonist activity with neuronal norepinephrine-reuptake inhibition in a single
      molecule. This duality of action should combine inhibition of ascending
      (afferent) pain-transmitting signals with activation of descending (efferent)
      pain-attenuating systems (e.g., diffuse noxious inhibitory controls). However,
      not all novel mechanisms of action impart the characteristics needed for an
      analgesic to be considered for first-line therapy. These key questions may help
      inform clinical decision making.

PMID- 28434284
TI  - Injection of basic fibroblast growth factor for unilateral vocal cord paralysis.
AB  - OBJECTIVE: Unilateral vocal cord paralysis (UVCP) not only induces severe
      dysphonia, but aspiration as well. Although laryngeal framework surgery is
      usually performed to treat this condition, the procedure is not tolerated by some
      patients. In the previous study, basic fibroblast growth factor (bFGF) injections
      for vocal cord scarring and sulcus have been reported to provide favorable
      outcomes while being minimally invasive. In this study, the authors
      retrospectively investigated phonological outcomes after bFGF injection in
      patients with UVCP. METHODS: This study was registered in University hospital
      Medical Information Network - Clinical Trials Registry (UMIN000019347). Nineteen
      patients with unilateral cord paralysis were treated with bFGF injection. The
      treatment regimen involved a single injection of 50 MUg of bFGF into the muscle
      layer. More than six months after the injection, aerodynamic and acoustic
      outcomes were examined. RESULTS: The voice handicap index, maximum phonation
      time, mean airflow rate, and pitch range improved significantly after injection
      of bFGF. No sex-related differences were observed in any phonological parameter.
      CONCLUSION: bFGF injection, an easy method and suitable as an office procedure,
      significantly improved the hoarseness caused by UVCP. It is expected to be widely
      adopted and effective adjunctive drugs, and procedures are anticipated to be
      developed.

PMID- 28434285
TI  - Aortic diameter at age 65 in men with newly diagnosed type 2 diabetes.
AB  - OBJECTIVES: Type 2 diabetes mellitus has been linked to a decreased risk for
      abdominal aortic aneurysm (aortic diameter >=30 mm, AAA) development in men. The
      aim of this study was to evaluate if such an effect is detectable already around
      the time of diabetes diagnosis. DESIGN: We cross-sectionally compared aortic
      diameter at ultrasound screening for AAA in 691 men aged 65 years with incipient
      or newly diagnosed type 2 diabetes (group A) with 18,262 65-year old control men
      without diabetes (group B). RESULTS: Aortic diameter did not differ between
      groups (18.8[17.4-20.8] vs. 19.0[17.5-28.7] mm; p = 0.43). AAA prevalence was
      2.5% in group A and 1.5% in group B (p = .010). In logistic regression taking
      group differences in body mass index (BMI), smoking, presence of atherosclerotic
      disease and hypertension into account, the difference in AAA prevalence was no
      longer significant (p = .15). Among men in group A, C-peptide (r = .093; p =
      .034), but not HbA1c (r = .060; p = .24) correlated with aortic diameter.
      CONCLUSION: Among 65 year old men aortic diameter and AAA prevalence do not
      differ between those with newly diagnosed type 2 diabetes and those without
      diabetes. Putative protective effects of type 2 diabetes mellitus against aortic
      dilatation and AAA development therefore probably occur later after diagnosis of
      diabetes.

PMID- 28434286
TI  - Degradation of triclosan and its main intermediates during the combined
      irradiation and biological treatment.
AB  - Triclosan is an extensively applied antimicrobial agent which has been frequently
      detected in the environment. In this paper, the degradation of triclosan and its
      main intermediates was investigated during the combined irradiation and
      biological treatment. The results showed that triclosan degradation increased
      with increase of absorbed dose, the removal efficiency of triclosan was 62%, 77%,
      87%, 91% and 94%, respectively at 1, 2, 3, 4 and 5 kGy. The final removal
      efficiency of triclosan after the combined irradiation and biological process was
      81%, 86%, 90%, 92% and 95%, respectively. During the irradiation process, two
      main intermediates, that is, 4,4'-2'-phenoxyphenol (Intermediate 1) and 4-chloro
      2'-phenoxyphenol (Intermediate 2) were detected, in which Intermediate 1
      dominated during the irradiation process. In the following biological treatment
      process, Intermediates 1 and 2 could be further degraded. In single biological
      treatment process, the final removal efficiency of triclosan was 54%, and
      Intermediates 1 and 2 were detected. Intermediate 1 could be biodegraded while
      Intermediate 2 could not. The concentration of Intermediate 2 increased during
      biological treatment process. In conclusion, irradiation as pre-treatment process
      can enhance the degradation of triclosan and improve the biodegradability of
      Intermediate 2. Combined irradiation and biological process can be promising for
      treating antibiotic-containing wastewater.

PMID- 28434288
TI  - Amyloid A (AA) amyloidosis in CByB6 mice: a model to study gastrointestinal
      amyloidosis.

PMID- 28434287
TI  - La "Donna di Ostuni", a case of eclampsia 28,000 years ago?
AB  - La "Donna di Ostuni", the Lady from Ostuni (fortified medieval city, on the
      southern Italian Adriatic coast) is the skeleton of "the human most ancient
      mother" ever found by paleoanthropologists, grave dated of 28,000 years BP. It
      concerns a 20-years-old woman buried with her baby in her womb estimated at 8
      months gestation. To date, the cause of the maternal-fetal deaths is qualified of
      unknown origin. We propose that eclampsia may be a possible explanation for these
      deaths (mother and baby together). Eclampsia (convulsions), the curse of human
      births (non-existent in other mammals), has been described since writings has
      existed 5000 years ago in all civilisations. This plausible description dating
      from Palaeolithic times, 28,000 years BP, long before the emergence of
      agriculture (10,000 years BP) may be an interesting milestone. Further, she was
      buried with a shell-made headdress, as represented in several "Venus" figurines
      retrieved in all the Eurasiatic area (notably the "Willemdorf Venus"). The
      authors propose a new hypothesis that this headdress could be a protective device
      for pregnant women not only for birthing, but also against the terrorising
      convulsions (eclampsia) which could happen in all human pregnancy, especially in
      the first ones (primiparae).

PMID- 28434289
TI  - Regulated expression of amyloidogenic immunoglobulin light chains in mice.

PMID- 28434290
TI  - Extended characterization of the novel co-isogenic C57BL/6J Prnp-/- mouse line.

PMID- 28434291
TI  - The importance of pre-clinical studies in animal models of TTR amyloidosis for
      the discovery of novel patient disease biomarkers.

PMID- 28434292
TI  - Prognostication of survival and progression to dialysis in AA amyloidosis.

PMID- 28434293
TI  - Severity and reversibility of cardiac dysfunction and residual concentration of
      amyloidogenic light chain predict overall survival of patients with AL
      amyloidosis who attain complete response.

PMID- 28434294
TI  - Establishment of a diagnostic center for amyloidosis in Japan by Kumamoto
      University.

PMID- 28434295
TI  - Standard heart failure medication in cardiac transthyretin amyloidosis: useful or
      harmful?

PMID- 28434296
TI  - Serum amyloid A (SAA) treatment enhances the recovery of aggravated polymicrobial
      sepsis in mice, whereas blocking SAA's invariant peptide results in early death.

PMID- 28434297
TI  - Efficiency of siRNA for removal of transthyretin V30M in a TTR leptomeningeal
      animal model.

PMID- 28434298
TI  - Response to bendamustine is associated with a survival advantage in a heavily
      pretreated patients with AL amyloidosis.

PMID- 28434299
TI  - First report of MYD88L265P somatic mutation in IgM-associated light chain
      amyloidosis.

PMID- 28434300
TI  - BRICHOS - an anti-amyloid chaperone: evaluation of blood-brain barrier
      permeability of Bri2 BRICHOS.

PMID- 28434301
TI  - An Asp to Asn mutation is a toxic trigger in beta-2 microglobulin: structure and
      biophysics.

PMID- 28434302
TI  - Fibrinogen A alpha-chain amyloidosis: a non-negligible cause of chronic kidney
      disease in dialysis patients.

PMID- 28434303
TI  - Familial wild-type transthyretin cardiomyopathy.

PMID- 28434304
TI  - Immunoparesis status in AL amyloidosis at diagnosis affects response and survival
      by regimen type.

PMID- 28434305
TI  - Transthyretin amyloidosis: a little history of hereditary amyloidosis.

PMID- 28434306
TI  - Myocardial uptake of 99mTc-DPD in patients with AL amyloidosis.

PMID- 28434307
TI  - Clinicopathological characteristics of a patient with ureteral amyloidosis.

PMID- 28434308
TI  - AA cardiomyopathy.

PMID- 28434309
TI  - An aggressive form of transthyretin amyloidosis.

PMID- 28434310
TI  - Diagnostic accuracy of new indirect ELISAs for free light-chain quantification in
      fat tissue of patients with AL amyloidosis.

PMID- 28434311
TI  - Apolipoprotein A-II accelerates reactive AA amyloidosis.

PMID- 28434312
TI  - Occurrence factors and clinical picture of iatrogenic transthyretin amyloidosis
      after domino liver transplantation.

PMID- 28434313
TI  - Clinical and 123I-SAP scintigraphy findings in three members from a family
      affected by AGel amyloidosis.

PMID- 28434314
TI  - Caloric restriction prevents the progression of murine AApoAII amyloidosis.

PMID- 28434315
TI  - Diflunisal compassive use in transthyretin hereditary amyloid polyneuropathy:
      report of a first Spanish experience.

PMID- 28434316
TI  - Serendipitous inhibition of Abeta and rVlambda6Wil amyloid fibril growth by bi
      functional peptides.

PMID- 28434317
TI  - The demographic, genetic, and clinical characteristics of Brazilian subjects
      enrolled in the Transthyretin Amyloidosis Outcomes Survey.

PMID- 28434318
TI  - Probing the structural requirements of polybasic peptides for effective and
      specific amyloid reactivity.

PMID- 28434320
TI  - A good clonal response to chemotherapy in AL amyloidosis is associated with
      improved quality of life and function at 1 year.

PMID- 28434319
TI  - The ever-growing understanding of transthyretin amyloidosis nephropathy.

PMID- 28434321
TI  - Renal outcomes of autologous stem cell transplantation among patients with light
      chain amyloidosis: a single centre Spanish experience.

PMID- 28434322
TI  - The demographic, genetic, and clinical characteristics of Latin American subjects
      enrolled in the Transthyretin Amyloidosis Outcomes Survey.

PMID- 28434323
TI  - Identification and quantification of urinary monoclonal proteins by capillary
      electrophoresis in AL amyloidosis.

PMID- 28434324
TI  - A simple test for AA amyloid.

PMID- 28434325
TI  - Antiamyloidogenic and proamyloidogenic chaperone effects of C-reactive protein
      and serum amyloid P component.

PMID- 28434326
TI  - Urinary albumin to creatinine ratio in diagnosis and risk stratification of renal
      AL amyloidosis.

PMID- 28434327
TI  - Clinicopathological and biochemical findings of late-onset hereditary
      transthyretin amyloidosis 16 years after liver transplantation: an autopsy case
      study.

PMID- 28434328
TI  - Transthyretin-related hereditary amyloidosis in an Argentinian family with TTR
      Tyr114Cys mutation.

PMID- 28434329
TI  - De novo hereditary (familial) amyloid polyneuropathy (FAP) in a FAP liver
      recipient.

PMID- 28434330
TI  - Significant association between renal function and area of amyloid deposition
      evident in kidney biopsy specimens in both AA and AL amyloidosis.

PMID- 28434332
TI  - Hereditary transthyretin amyloidosis associated with a transthyretin variant
      Thr59Arg.

PMID- 28434331
TI  - Disruption of blood-nerve barriers in hereditary transthyretin (ATTR)
      amyloidosis.

PMID- 28434333
TI  - FAP plasma-induced cellular toxicity.

PMID- 28434334
TI  - Domino liver transplantation: full-length transthyretin in donor and recipient
      patients with ATTR Val30Met amyloidosis.

PMID- 28434335
TI  - Insulin: a diagnostic warning.

PMID- 28434336
TI  - Introduction.

PMID- 28434337
TI  - Treatment of transthyretin cardiomyopathy with a TTR-specific antisense
      oligonucleotide (IONIS-TTRRx).

PMID- 28434338
TI  - Sensitive and reliable immunohistochemical typing of 21 different amyloid classes
      in 782 patients using amyloid-type specific antibodies directed against the
      amyloidotic conformation. With comments on the gold standard debate.

PMID- 28434339
TI  - Global epidemiology of transthyretin hereditary amyloid polyneuropathy: a
      systematic review.

PMID- 28434340
TI  - Long-term effects of liver transplantation on small-fiber dysfunction in Japanese
      transthyretin (ATTR) V30M hereditary amyloidosis with polyneuropathy (FAP).

PMID- 28434341
TI  - Acceleration of alpha-synuclein aggregation.

PMID- 28434342
TI  - Patterns of relapse after upfront bortezomib therapy in AL amyloidosis.

PMID- 28434343
TI  - Patients with AL amyloidosis and low free light-chain burden have distinct
      clinical features and outcome.

PMID- 28434344
TI  - N-terminal region of serum amyloid A3 is responsible for up-regulation of MUC2
      mRNA expression in mouse epithelial cells.

PMID- 28434345
TI  - Epidemiological and clinical characteristics of persons with transthyretin
      hereditary amyloid polyneuropathy: a global synthesis of 532 cases.

PMID- 28434346
TI  - Refine penetrance estimates in the main pathogenic variants of transthyretin
      hereditary (familial) amyloid polyneuropathy (TTR-FAP) using a new non-parametric
      approach (NPSE).

PMID- 28434347
TI  - Interim analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal
      antibody 11-1F4 in patients with AL amyloidosis.

PMID- 28434349
TI  - Different population - different prevalence or, what is going on in the European
      brown hare (Lepus europaeus).

PMID- 28434348
TI  - Six-minute walk test (6MWT) in AL amyloidosis - baseline and 12-month follow-up
      after chemotherapy.

PMID- 28434350
TI  - Antibody therapy for transthyretin-related hereditary amyloid polyneuropathy:
      another therapeutic option.

PMID- 28434351
TI  - End-stage renal failure due to transthyretin amyloidosis after liver
      transplantation: outcomes in 19 registry cases.

PMID- 28434352
TI  - The challenging histological diagnosis of transthyretin (ATTR) amyloidosis.

PMID- 28434353
TI  - A novel murine system for validating the specific targeting of peptides to light
      chain associated (AL) amyloid.

PMID- 28434354
TI  - Preliminary characterization of a novel peptide-Fc-fusion construct for targeting
      amyloid deposits.

PMID- 28434355
TI  - Recruitment of human light chain proteins by synthetic fibrils is dependent on
      disease state and may be used to predict amyloidogenic propensity.

PMID- 28434356
TI  - A bifunctional peptide, "peptope", for pre-targeting antibody 7D8 to systemic
      amyloid deposits.

PMID- 28434357
TI  - Retinol binding protein 4 (RBP4) concentration identifies V122I transthyretin
      cardiac amyloidosis.

PMID- 28434359
TI  - Thioflavin T: not an all-rounder, but a trustworthy friend for over 27 years.

PMID- 28434358
TI  - Iatrogenic systemic transthyretin amyloid deposits in a case with domino liver
      transplantation: an autopsy case study.

PMID- 28434360
TI  - A case with a novel variant transthyretin A36D presenting cardiac phenotype.

PMID- 28434361
TI  - Feasibility study of cardiac magnetic resonance elastography in cardiac
      amyloidosis.

PMID- 28434362
TI  - In vitro and in vivo assessment of novel derivatives for detecting various
      amyloid deposits.

PMID- 28434363
TI  - Infrared spectroscopic imaging: a label free approach for the detection of
      amyloidosis in human tissue biopsies.

PMID- 28434364
TI  - The Swedish landscape of hereditary ATTR amyloidosis.

PMID- 28434365
TI  - Identification of amyloid precursor protein from autopsy and biopsy specimens
      using LMD-LC-MS/MS: the experience at Kumamoto University.

PMID- 28434366
TI  - Recommendations from the Amyloidosis Research Consortium Educational Roundtable
      at the American College of Cardiology Annual Meeting, 1 April 2016.

PMID- 28434367
TI  - A late-onset case of hereditary transthyretin amyloidosis with a novel compound
      heterozygous mutation.

PMID- 28434368
TI  - Outcome of very young (<=40 years) patients with immunoglobulin light chain (AL)
      amyloidosis.

PMID- 28434369
TI  - Seed-dependent templating of murine AA amyloidosis.

PMID- 28434370
TI  - Transthyretin (ATTR) amyloidosis nephropathy: lessons from a TTR stabilizer
      molecule.

PMID- 28434371
TI  - Immunoparesis in newly diagnosed AL amyloidosis is a marker for response and
      survival.

PMID- 28434372
TI  - Doxycycline-tauroursodeoxycholic acid treatment: effects in the heart of a
      transthyretin V30M transgenic mouse model.

PMID- 28434373
TI  - Thermal shift assay for evaluation of transthyretin stability in plasma.

PMID- 28434374
TI  - Cardiac amyloid imaging with 18F-florbetaben positron emission tomography: a
      pilot study.

PMID- 28434375
TI  - The role of adaptive trial designs in drug development.
AB  - INTRODUCTION: Clinical development of new drugs is a long and costly process.
      There is a need to find solutions which can improve and shorten this process. By
      introducing flexibility in to the design of clinical trials, adaptive design
      contributes to this improvement and allows to reach drug development decisions in
      a quicker way. Areas covered: We review the main methodological approaches to
      adaptive trial design, introducing key statistical concepts. For each phase of
      the clinical development, different uses and implementations of adaptive trial
      (AD) design are presented and examples of recent clinical trials are given. The
      guidance documents issued by the US and European regulatory authorities are also
      presented. Expert commentary: Despite inevitable challenges, prospects of this
      rapidly evolving approach to drug development are important. Controlling the risk
      of type 1 error and the potential operational risks which may be associated with
      adaptive trial strategy is paramount in late phase studies. However, with new
      methodological work, these risks are now well controlled and adaptive trial
      design will certainly shape the future of drug development.

PMID- 28434376
TI  - Pre-clinical and clinical development of the first placental malaria vaccine.
AB  - INTRODUCTION: Malaria during pregnancy is a massive health problem in endemic
      areas. Placental malaria infections caused by Plasmodium falciparum are
      responsible for up to one million babies being born with a low birth weight every
      year. Significant efforts have been invested into preventing the condition. Areas
      covered: Pub Med was searched using the broad terms 'malaria parasite placenta'
      to identify studies of interactions between parasite and host, 'prevention of
      placental malaria' to identify current strategies to prevent placental malaria,
      and 'placental malaria vaccine' to identify pre-clinical vaccine development.
      However, all papers from these searches were not systematically included. Expert
      commentary: The first phase I clinical trials of vaccines are well underway.
      Trials testing efficacy are more complicated to carry out as only women that are
      exposed to parasites during pregnancy will contribute to endpoint measurements,
      further it may require extensive follow-up to establish protection. Future second
      generation vaccines may overcome the inherent challenges in making an effective
      placental malaria vaccine.

PMID- 28434377
TI  - A primary extraskeletal osteosarcoma of the mesentery: a case report.
AB  - Extraskeletal osteosarcoma is a rare and invasive malignancy, typically located
      in the soft tissue without attachment to the skeleton. The present study reports
      a case of a primary mesenteric extraskeletal osteosarcoma of a 71-year-old woman.
      The patient complained of an incomplete defecation. Colonoscopy showed an ulcer
      with impression of external compression of the sigmoid. An additional abdominal
      computed tomography (CT) scan revealed a large, almost completely calcified, mass
      in the left lower abdomen causing hydronephrosis of the left kidney. The patient
      underwent surgery and the mass was resected completely. The histopathological
      diagnosis was a primary abdominal extraskeletal osteosarcoma arising from the
      mesocolon with local invasion of the sigmoid. She was in follow-up without
      adjuvant chemo- or radiotherapy. Five months after initial surgery the tumor
      recurred with widespread peritoneal metastasis.

PMID- 28434378
TI  - Performance properties, lactic acid specific migration and swelling by simulant
      of biodegradable poly(lactic acid)/nanoclay multilayer films for food packaging.
AB  - The aim of the study was the development of a multifunctional, high-performance,
      fully biodegradable multilayer polylactic acid (PLA) film for food packaging
      applications. In particular, sealable multilayer PLA-clay nanocomposite systems
      with different layouts in terms of composition and relative thickness of the
      layers, all consisting of a PLA-clay nanocomposite layer between two pure PLA
      layers for direct food contact, were designed and produced by blown film co
      extrusion. The films obtained were analysed for their morphology, functional
      properties and lactic acid (LA)-specific migration in 50% ethanol. The results
      showed that, with respect to the unfilled multilayer system, taken as a
      reference, the nanocomposite films had significant improvements, up to about 40%,
      in their barriers to oxygen and tensile strengths, and resulted in being more
      easily sealable over a wide heat-sealing temperature range (80-100 degrees C)
      with higher seal strength. Moreover, all films had LA migrations always well
      below the former generic overall migration limit of 60 mg kg-1 food (10 mg dm-2)
      of European Union Regulation No. 10/2011 (deleted by the amending Regulation No.
      2016/1416), even if their morphology was strongly modified during the migration
      tests due to the strong swelling action of the used simulant (simulant D1 = 50%
      ethanol (aq.) (v/v)) towards PLA.

PMID- 28434379
TI  - Hick's law for choice reaction time: A review.
AB  - In 1952, W. E. Hick published an article in the Quarterly Journal of Experimental
      Psychology, "On the rate of gain of information." It played a seminal role in the
      cognitive revolution and established one of the few widely acknowledged laws in
      psychology, relating choice reaction time to the number of stimulus-response
      alternatives (or amount of uncertainty) in a task. We review the historical
      context in which Hick conducted his study and describe his experiments and
      theoretical analyses. We discuss the article's immediate impact on researchers,
      as well as challenges to and shortcomings of Hick's law and his analysis,
      including effects of stimulus-response compatibility, practice, very large set
      sizes and sequential dependencies. Contemporary modeling developments are also
      described in detail. Perhaps most impressive about Hick's law is that it
      continues to spawn research efforts to the present and that it is regarded as a
      fundamental law of interface design for human-computer interaction using
      technologies that did not exist at the time of Hick's research.

PMID- 28434380
TI  - High poly to low poly workflows for real-time rendering.
AB  - This paper outlines a digital workflow that allows artists to add visual detail
      to 3D models whilst adhering to the strict polygonal budget that is vital to
      successfully render in real-time. Two versions of a model - a high-poly model,
      and a low-poly model - are produced to create a 2D normal map through a process
      known as 'baking', to achieve the illusion of the high resolution detail on the
      low-resolution model.

PMID- 28434381
TI  - IMI Gallery - PR.

PMID- 28434383
TI  - Bioimages 2016.

PMID- 28434382
TI  - The BMA Patient Information Awards: What's the history?
AB  - The British Medical Association (BMA) Patient Information Awards has been running
      since 1997. This article briefly looks back at it's history and origins.

PMID- 28434384
TI  - A healthbot future: utopian, dystopian, distraction?

PMID- 28434385
TI  - Digital curation and online resources: digital scanning of surgical tools at the
      royal college of physicians and surgeons of Glasgow for an open university
      learning resource.
AB  - Collection preservation is essential for the cultural status of any city.
      However, presenting a collection publicly risks damage. Recently this drawback
      has been overcome by digital curation. Described here is a method of digitisation
      using photogrammetry and virtual reality software. Items were selected from the
      Royal College of Physicians and Surgeons of Glasgow archives, and implemented
      into an online learning module for the Open University. Images were processed via
      Agisoft Photoscan, Autodesk Memento, and Garden Gnome Object 2VR. Although
      problems arose due to specularity, 2VR digital models were developed for online
      viewing. Future research must minimise the difficulty of digitising specular
      objects.

PMID- 28434386
TI  - Flibanserin - the female Viagra?
AB  - This article provides a clinically relevant review of the first medication
      approved by the US Food and Drug Administration for hypoactive sexual desire
      disorder (HSDD) in premenopausal women. In this short piece, the human sexual
      response cycle and its relevance to HSDD will be described as well as the
      pharmacological mechanism of action of flibanserin. Finally, efficacy and safety
      data of this new medication will be summarised.

PMID- 28434387
TI  - Cost-utility of biological treatment sequences for luminal Crohn's disease in
      Europe.
AB  - BACKGROUND: This study aims to compare the cost-effectiveness of treatment
      sequences with available biologics, including adalimumab (ADA), biosimilar
      infliximab (bsIFX), originator infliximab (IFX) and vedolizumab (VEDO) for
      luminal Crohn's disease in nine European countries. METHODS: A Markov-model was
      constructed to simulate five-year medical costs and quality-adjusted life years
      (QALYs). Data on clinical efficacy were obtained from randomised controlled
      trials. Country-specific unit costs, discount rates and a third-party payer
      perspective were applied. RESULTS: The bsIFX versus conventional therapy resulted
      in the most favourable incremental cost-utility ratios (ICURs) ranging from
      ?34,580 (Hungary) to ?77,062/QALY (Sweden). Compared to bsIFX, the bsIFX-ADA
      sequence was more cost-effective than the bsIFX-VEDO sequence with ICURs varying
      between ?70,277 (France) and ?162,069/QALY (Germany). The ICURs of the bsIFX-ADA
      VEDO sequence versus the bsIFX-ADA strategy were between ?206,266 (The
      Netherlands) and ?363,232/QALY (Spain). CONCLUSION: We are the first to compare
      cost-effectiveness of multiple biological sequences for luminal Crohn's disease.
      Based on our findings, bsIFX can be recommended as a first-line treatment in
      patients unresponsive to conventional treatments. While biological sequences only
      slightly differ in their associated health gains, their costs vary greatly. The
      bsIFX-ADA-VEDO seems to be the most cost-effective sequence of the available
      biologics across Europe.

PMID- 28434388
TI  - MicroRNA-221-3p is up-regulated and serves as a potential biomarker in pancreatic
      cancer.
AB  - It has been demonstrated that circulating MicroRNAs (miRNAs) could be potential
      biomarkers for cancer diagnosis and prognosis. For pancreatic cancer (PCa),
      little is known about miR-221-3p biological function or its prognostic value. In
      the current study, we profiled miR-221-3p expression in PCa cell lines. Compared
      with normal pancreases ductal epithelial cells, miR-221-3p is up-regulated in all
      PCa cell lines analysed. In SW1990 cells, overexpression of miR-221-3p increased
      cell proliferation and inhibited apoptosis, while inhibition of miR-221-3p
      decreased cell growth rate and promoted apoptosis. Compared with adjacent non
      tumour tissues, miR-221-3p was up-regulated in all 21 PCa tissues. Expression
      level of miR-221-3p was investigated in plasma and statistical analyses showed
      that circulating miR-221-3p expression level was correlated with distant
      metastasis and TNM stages. The receiver-operating characteristic (ROC) curves and
      the area under the ROC curve (AUC) suggested that the diagnostic efficacy for
      distant metastasis of miR-221-3p is better than CA19-9 (AUC: 0.689 vs. 0.587). To
      summary, we found miR-221-3p could promote cell proliferation and inhibit
      apoptosis in PCa cells and circulating miR-221-3p could serve as a biomarker for
      PCa.

PMID- 28434389
TI  - Evaluation of the protective effect of Botulinum toxin type A injection on otitis
      media with effusion.
AB  - OBJECTIVE: This study makes an analysis of the effect of Botulinum toxin type A
      on otitis media with effusion in rats. METHOD: As part of the study, 24 male
      Wistar Albino rats were divided into three groups: Group 1: Botulinum toxin Type
      A and Histamine (intratympanic 0.2 ml = 20 unit BTA); Group 2: Saline and
      Histamine (intratympanic 0.2 ml 0.9%); Group 3: Histamine (intratympanic 0.2 ml).
      Histamine (intratympanic 0.2 ml) was administered into the right ear for all
      groups. DPOAE and ABR tests were carried out on days 5, 10, 15 and 20 from the
      beginning of the study. RESULTS: There was no significant difference between
      DPOAE and ABR scores of the groups. In each group, the DPOAE scores for the right
      ear significantly decreased on day 5 when compared to the basal scores. In each
      group, there was no significant difference between days 5, 10 and 15 for the
      right ear. CONCLUSIONS: Botulinum toxin type A blocked the secretion of glands in
      the middle ear and showed no effect to prevent the formation of serous otitis. In
      addition, it was found out that Botulinum toxin did not lead to any morphological
      change in the cochlea.

PMID- 28434390
TI  - How Preferences for Continuity and Access Differ Between Multimorbidity and
      Healthy Patients in a Team Care Setting.
AB  - INTRODUCTION: Team-based care has become an essential part of modern medical
      practice. Patient-centered medical homes often struggle to balance the dual
      competing goals of acute access and continuity of care. Multimorbidity patients
      may value continuity more than healthy patients, and thus may prefer to wait to
      see their primary care physician (PCP). METHODS: A total of 1700 randomly
      selected healthy adults and multimorbidity patients were asked to rate
      satisfaction with care and presented with 4 acute and 4 chronic scenarios to
      choose an access and continuity preference in an anonymous mailed survey.
      RESULTS: In all, 770 responses were obtained. All respondents preferred to be
      seen 2.5 days sooner for acute appointments. Multimorbidity patients preferred to
      wait 0.28 days longer for acute issues to see their PCP. Patients who were not
      satisfied with their care team preferred to wait 0.75 days to see their PCP.
      Those not satisfied with their PCP choose to be seen 0.38 days sooner by their
      care team or any physician. CONCLUSIONS: All patients prefer continuity of care
      with their PCP for chronic disease management and value quick access to care for
      acute problems. For acute visits, multimorbidity patients prefer to wait longer
      to see their PCP than healthy adults. Satisfaction also plays an important role
      in patients' willingness to wait for an appointment with their PCP.

PMID- 28434391
TI  - A novel Integrated Clinical Apprenticeship: transforming medical students into
      student doctors.

PMID- 28434392
TI  - Does the EQ-5D capture the concerns measured by the Palliative care Outcome
      Scale? Mapping the Palliative care Outcome Scale onto the EQ-5D using statistical
      methods.
AB  - BACKGROUND: The main measure to generate utility data for economic evaluations is
      the EQ-5D, but no study has tested whether or how to map from palliative care
      measures to the EQ-5D. AIMS: To assess the level of conceptual overlap between
      palliative outcomes and the EQ-5D, and the feasibility of mapping between them to
      obtain utilities for the Palliative care Outcome Scale. DESIGN: A cross-sectional
      secondary analysis of data from three studies. SETTING/PARTICIPANTS: Patients
      receiving palliative care and bereaved relatives, recruited from three tertiary
      National Health Service hospitals in South London. METHODS: The overlap between
      both measures was assessed using principal component analysis. The Palliative
      care Outcome Scale was mapped onto the EQ-5D using three regression models.
      RESULTS: Spearman's correlations between both instruments were low (mean rho =
      0.11). The principal component analysis showed the Palliative care Outcome Scale
      is associated with only two EQ-5D dimensions (pain; and anxiety/depression). No
      Palliative care Outcome Scale items loaded onto the mobility, self-care and usual
      activities dimensions of the EQ-5D. The mapping models performed poorly at
      predicting utilities from Palliative care Outcome Scale data (mean absolute error
      >0.3 and R2 <0.10). Hence, none of the models can be recommended as acceptable
      for calculating utilities from Palliative care Outcome Scale responses.
      CONCLUSION: Differences between the Palliative care Outcome Scale and the EQ-5D
      do not undermine the qualities of either instrument when used for their own
      purposes. However, due to conceptual differences, the EQ-5D does not capture some
      of the concerns measured by the Palliative care Outcome Scale, and therefore,
      mapping onto the EQ-5D is unlikely to provide an appropriate basis for estimating
      utilities for conducting economic evaluations in palliative care studies.

PMID- 28434394
TI  - Assessing Research Benefits: Practical Ethicist.

PMID- 28434393
TI  - Barriers and Strategies Related to Qualitative Research on Genetic Ancestry
      Testing in Indigenous Communities.
AB  - Conducting genetics-related research with populations that have historically
      experienced considerable harm and little benefit from genetics research poses
      unique challenges for understanding community-based perceptions of new genetic
      technologies. This article identifies challenges and strategies for collecting
      qualitative data on the perceptions of direct-to-consumer (DTC) Genetic Ancestry
      tests (GAT) among diverse Indigenous communities. Based on a 3-year project
      related to perceptions, attitudes, and values associated with genetic ancestry
      testing among diverse Indigenous communities in Oklahoma, the engagement process
      revealed specific opportunities to improve the process of qualitative data
      collection related to GAT, and more broadly, to conduct genetics-related research
      with Indigenous communities in culturally and methodologically appropriate ways.
      Priority areas include issues related to participant recruitment and tribal
      advisory boards, challenges of self-identification as a recruitment mechanism,
      and the necessity of including Indigenous researchers in all aspects of the
      research process.

PMID- 28434395
TI  - Would Adults with Autism be less likely to Bury the Survivors? An Eye Movement
      Study of Anomalous Text Reading.
AB  - In a single eye movement experiment we investigated the effects of context on the
      time course of local and global anomaly processing during reading in adults with
      Autism Spectrum Disorder (ASD). In one condition short paragraph texts contained
      anomalous target words. Detection of the anomaly was only possible through
      evaluation of word meaning in relation to the global context of the whole
      paragraph (Passage Level Anomalies). In another condition the anomaly could be
      detected via computation of a local thematic violation within a single sentence
      embedded in the paragraph (Sentence Level Anomalies). For the sentence level
      anomalies the ASD group, in contrast with the typically developing (TD) group,
      showed early detection of the anomaly as indexed by regressive eye movements from
      the critical target word upon fixation. Conversely, for the passage level
      anomalies, and in contrast with the ASD group, the TD group showed early
      detection of the anomaly, with increased regressive eye movements once the
      critical word had been fixated. The reversal of the pattern of regression path
      data for the two groups, for the sentence and passage level anomalies, is
      discussed in relation to cognitive accounts of ASD.

PMID- 28434397
TI  - Watching the availability and use of rapid diagnostic tests (RDTs) and
      artemisinin-based combination therapy (ACT).
AB  - At the turn of this new century and after much debate, the malaria community
      reckoned with failing first line therapies and moved to a global recommendation
      for deployment of an artemisinin-based combination therapy (ACT) to treat
      infections due to Plasmodium falciparum. No one said it was going to be easy.
      This series in the Malaria Journal reports longitudinal snapshots of how the core
      pillar of malaria elimination of ensuring universal access to malaria diagnosis
      and treatment is faring-it is safe to say "not so well". Core issues that must be
      addressed to ensure universal access to diagnosis and treatment, and achieve
      elimination, include lack of access to these essential services for those with
      malaria and the lack of a common effective service delivery approach to ensure
      high quality diagnosis and treatment, especially in the private sector which
      provides the bulk of malaria case management services in many settings. The
      barriers to universal access to high quality diagnosis and treatment for malaria
      will need to be addressed if malaria elimination is to remain a real possibility
      in the foreseeable future.

PMID- 28434396
TI  - Immunotherapy in hematologic malignancies: past, present, and future.
AB  - The field of immunotherapy in cancer treatments has been accelerating over recent
      years and has entered the forefront as a leading area of ongoing research and
      promising therapies that have changed the treatment landscape for a variety of
      solid malignancies. Prior to its designation as the Science Breakthrough of the
      Year in 2013, cancer immunotherapy was active in the treatment of hematologic
      malignancies. This review provides a broad overview of the past, present, and
      potential future of immunotherapy in hematologic malignancies.

PMID- 28434398
TI  - The use of immunotherapy in the treatment of melanoma.
AB  - Patients with advanced melanoma have a compromised anti-tumor immune response
      leading to tumor immune tolerance and a tumor microenvironment conducive to
      disease progression. Immunotherapy that successfully overcomes this tumor
      mediated immune suppression has made the greatest impact in the management of
      this disease over the past few years. This progress through immunotherapy builds
      upon earlier successes that interferon-alpha had in the treatment of melanoma in
      the adjuvant setting, as well as that of high-dose interleukin-2 in advanced
      melanoma. The development of immune checkpoint inhibitors has led to dramatic
      clinical activity in advanced melanoma. In particular, anti-CTLA4 and anti-PD1
      monoclonal antibodies have taken us forward into the realm of longer survival and
      durable responses with the possibility of cure in a continuously increasing
      proportion of patients. Combination immunotherapeutic strategies and novel
      immunotherapeutic agents are being tested at an accelerated pace where the
      outlook for long-term survival benefits for the majority of patients appears
      brighter than ever.

PMID- 28434399
TI  - The next generation of immunotherapy: keeping lung cancer in check.
AB  - Lung cancer is the deadliest malignancy with more cancer deaths per year than the
      next three cancers combined. Despite remarkable advances in targeted therapy,
      advanced lung cancer patients have not experienced a significant improvement in
      mortality. Lung cancer has been shown to be immunogenic and responsive to
      checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1
      dampen T cell activation and allow tumors to escape the adaptive immune response.
      Response rates in patients with pretreated, advanced NSCLC were much higher and
      more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic
      chemotherapy. Therefore, PD-1 inhibitors such as nivolumab and pembrolizumab were
      rapidly approved for both squamous and nonsquamous lung cancer in the pretreated
      population. The advent of these new therapies have revolutionized the treatment
      of lung cancer; however, the majority of NSCLC patients still do not respond to
      PD-1/PD-L1 inhibition leaving an unmet need for a large and growing
      population.Immunotherapy combinations with chemotherapy, radiation therapy, or
      novel immunomodulatory agents are currently being examined with the hope of
      achieving higher response rates and improving overall survival rate. Chemotherapy
      and radiation therapy has been theorized to increase the release of tumor antigen
      leading to increased responses with immunotherapy. However, cytotoxic
      chemotherapy and radiation therapy may also destroy actively proliferating T
      cells. The correct combination and order of therapy is under investigation. The
      majority of patients who do respond to immunotherapy have a durable response
      attributed to the effect of adaptive immune system's memory. Unfortunately, some
      patients' tumors do progress afterward and investigation of checkpoint blockade
      resistance is still nascent.This review will summarize the latest efficacy and
      safety data for early and advanced NSCLC in both the treatment-naive and
      pretreated settings. The emerging role of immunotherapy for the treatment of
      small cell lung cancer and malignant mesothelioma will also be discussed.

PMID- 28434400
TI  - Role of modern immunotherapy in gastrointestinal malignancies: a review of
      current clinical progress.
AB  - Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with
      a huge disease burden worldwide. There is clearly a significant unmet need for
      new drugs and therapies to further improve the treatment outcomes of GI
      malignancies. Immunotherapy is a novel treatment strategy that is emerging as an
      effective and promising treatment option against several types of cancers. CTLA-4
      and PD-1 are critical immune checkpoint molecules that negatively regulate T cell
      activation via distinct mechanisms. Immune checkpoint blockade with antibodies
      directed against these pathways has already shown clinical efficacy that has led
      to their FDA approval in the treatment of several solid tumors including
      melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma,
      and head and neck cancer. This review will summarize the current clinical
      progress of modern immunotherapy in the field of GI tumors, with a special focus
      on immune checkpoint blockade.

PMID- 28434401
TI  - Ivermectin to reduce malaria transmission I. Pharmacokinetic and pharmacodynamic
      considerations regarding efficacy and safety.
AB  - Ivermectin is an endectocide that has been used broadly in single dose community
      campaigns for the control of onchocerciasis and lymphatic filariasis for more
      than 30 years. There is now interest in the potential use of ivermectin regimens
      to reduce malaria transmission, envisaged as community-wide campaigns tailored to
      transmission patterns and as complement of the local vector control programme.
      The development of new ivermectin regimens or other novel endectocides will
      require integrated development of the drug in the context of traditional
      entomological tools and endpoints. This document examines the main
      pharmacokinetic and pharmacodynamic parameters of the medicine and their
      potential influence on its vector control efficacy and safety at population
      level. This information could be valuable for trial design and clinical
      development into regulatory and policy pathways.

PMID- 28434402
TI  - Implementing the communication for development strategy to improve knowledge and
      coverage of measles vaccination in western Chinese immunization programs: a
      before-and-after evaluation.
AB  - BACKGROUND: Communication for Development (C4D) is a strategy promoted by the
      United Nations Children's Fund to foster positive and measurable changes at the
      individual, family, community, social, and policy levels of society. In western
      China, C4D activities have previously been conducted as part of province-level
      immunization programs. In this study, we evaluated the association of C4D with
      changes in parental knowledge of immunization services, measles disease, and
      measles vaccine, and changes in their children's measles vaccine coverage.
      METHODS: From April 2013 to April 2014, C4D activities were implemented as part
      of provincial immunization programs in the Inner Mongolia, Guangxi, Chongqing,
      Guizhou, Tibet, Shaanxi, Gansu, Ningxia, and Qinghai provinces. We used a before
      and-after study design and employed face-to-face interviews to assess changes in
      parental knowledge and vaccination coverage. RESULTS: We surveyed 2 107
      households at baseline and 2 070 households after 1 year of C4D activities.
      Following C4D, 95% of caregivers were aware of the vaccination record check
      requirement for entry into kindergarten and primary school; 80% of caregivers
      were aware that migrant children were eligible for free vaccination; more than
      70% of caregivers knew that measles is a respiratory infectious disease; and 90%
      of caregivers knew the symptoms of measles. Caregivers' willingness to take their
      children to the clinic for vaccination increased from 51.3% at baseline to 67.4%
      in the post-C4D survey. Coverage of one-dose measles-containing vaccine (MCV)
      increased from 83.8% at baseline to 90.1% after C4D. One-dose MCV coverage was
      greater than 95% in the Guangxi, Shaanxi, and Gansu provinces. Two-dose MCV
      coverage increased from 68.5 to 77.6%. House-to-house communication was the most
      popular C4D activity among caregivers (91.6% favoring), followed by posters and
      educational talks (64.8 and 49.9% favoring). CONCLUSIONS: C4D is associated with
      increased caregiver knowledge about measles, increased willingness to seek
      immunization services for their children, and increased measles vaccination
      coverage. Tailored communication strategies based on insights gained from these
      analyses may be able to increase vaccination coverage in hard-to-reach areas. C4D
      should be considered for larger scale implementation in China.

PMID- 28434404
TI  - Recent advances in cancer immunotherapy.

PMID- 28434403
TI  - Immunotherapy in genitourinary malignancies.
AB  - Treatment of cancer patients involves a multidisciplinary approach including
      surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic
      disease are treated with combination chemotherapies or targeted agents. These
      cytotoxic agents have good response rates and achieve palliation; however,
      complete responses are rarely seen. The field of cancer immunology has made rapid
      advances in the past 20 years. Recently, a number of agents and vaccines, which
      modulate the immune system to allow it to detect and target cancer cells, are
      being developed. The benefit of these agents is twofold, it enhances the ability
      the body's own immune system to fight cancer, thus has a lower incidence of side
      effects compared to conventional cytotoxic chemotherapy. Secondly, a small but
      substantial number of patients with metastatic disease are cured by immunotherapy
      or achieve durable responses lasting for a number of years. In this article, we
      review the FDA-approved immunotherapy agents in the field of genitourinary
      malignancies. We also summarize new immunotherapy agents being evaluated in
      clinical studies either as single agents or as a combination.

PMID- 28434405
TI  - Ivermectin to reduce malaria transmission II. Considerations regarding clinical
      development pathway.
AB  - The development of ivermectin as a complementary vector control tool will require
      good quality evidence. This paper reviews the different eco-epidemiological
      contexts in which mass drug administration with ivermectin could be useful.
      Potential scenarios and pharmacological strategies are compared in order to help
      guide trial design. The rationale for a particular timing of an ivermectin-based
      tool and some potentially useful outcome measures are suggested.

PMID- 28434406
TI  - Efavirenz-based simplification after successful early lopinavir-boosted-ritonavir
      based therapy in HIV-infected children in Burkina Faso and Cote d'Ivoire: the
      MONOD ANRS 12206 non-inferiority randomised trial.
AB  - BACKGROUND: The 2016 World Health Organization guidelines recommend all children
      <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens.
      But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income
      countries, including limited availability, requires refrigeration, interactions
      with anti-tuberculous drugs, twice-daily dosing, poor palatability in young
      children, and higher cost than non-nucleoside reverse transcriptase inhibitor
      (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children
      aged <2 years raises operational challenges that could be simplified by switching
      to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to
      date, EFV is not recommended in children <3 years. METHODS: The MONOD ANRS 12026
      study is a phase 3 non-inferiority open-label randomised clinical trial conducted
      in Abidjan, Cote d'Ivoire, and Ouagadougou, Burkina Faso (ClinicalTrial.gov
      registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and
      treated before the age of 2 years with 12-15 months of suppressive twice-daily
      LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were
      randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine
      (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily
      combination zidovudine ( ZDV) or  ABC + 3TC + LPV/r (referred to as LPV). The
      primary endpoint was the difference in the proportion of children with
      virological suppression by 12 months post-randomisation between arms (14% non
      inferiority bound, Chi-squared test). RESULTS: Between May 2011 and January 2013,
      156 children (median age 13.7 months) were initiated on ART. After 12-15 months
      on ART, 106 (68%) were randomised to one of the two treatment arms (54 LPV, 52
      EFV); 97 (91%) were aged <3 years. At 12 months post-randomisation, 46 children
      (85.2%) from LPV versus 43 (82.7%) from EFV showed virological suppression
      (defined as a VL <500 copies/mL; difference, 2.5%; 95% confidence interval (CI), 
      11.5 to 16.5), whereas seven (13%) in LPV and seven (13.5%) in EFV were classed
      as having virological failure (secondary outcome, defined as a VL >=1000
      copies/mL; difference, 0.5%; 95% CI, -13.4 to 12.4). No significant differences
      in adverse events were observed, with two adverse events in LPV (3.7%) versus
      four (7.7%) in EFV (p = 0.43). On genotyping, 13 out of 14 children with
      virological failure (six out of seven EFV, seven out of seven LPV) had a drug
      resistance mutation: nine (five out of six EFV, four out of seven LPV) had one or
      more major NNRTI-resistance mutations whereas none had an LPV/r-resistance
      mutation. CONCLUSIONS: At the VL threshold of 500 copies/mL, we could not
      conclusively demonstrate the non-inferiority of EFV on viral suppression compared
      to LPV because of low statistical power. However, non-inferiority was confirmed
      for a VL threshold of <1000 copies/mL. Resistance analyses highlighted a high
      frequency of NNRTI-resistance mutations. A switch to an EFV-based regimen as a
      simplification strategy around the age of 3 years needs to be closely monitored.
      TRIAL REGISTRATION: ClinicalTrial.gov registry n degrees  NCT01127204 , 19 May
      2010.

PMID- 28434408
TI  - SECURE INTERNET OF THINGS-BASED CLOUD FRAMEWORK TO CONTROL ZIKA VIRUS OUTBREAK.
AB  - OBJECTIVES: Zika virus (ZikaV) is currently one of the most important emerging
      viruses in the world which has caused outbreaks and epidemics and has also been
      associated with severe clinical manifestations and congenital malformations.
      Traditional approaches to combat the ZikaV outbreak are not effective for
      detection and control. The aim of this study is to propose a cloud-based system
      to prevent and control the spread of Zika virus disease using integration of
      mobile phones and Internet of Things (IoT). METHODS: A Naive Bayesian Network
      (NBN) is used to diagnose the possibly infected users, and Google Maps Web
      service is used to provide the geographic positioning system (GPS)-based risk
      assessment to prevent the outbreak. It is used to represent each ZikaV infected
      user, mosquito-dense sites, and breeding sites on the Google map that helps the
      government healthcare authorities to control such risk-prone areas effectively
      and efficiently. RESULTS: The performance and accuracy of the proposed system are
      evaluated using dataset for 2 million users. Our system provides high accuracy
      for initial diagnosis of different users according to their symptoms and
      appropriate GPS-based risk assessment. CONCLUSIONS: The cloud-based proposed
      system contributed to the accurate NBN-based classification of infected users and
      accurate identification of risk-prone areas using Google Maps.

PMID- 28434407
TI  - Ivermectin to reduce malaria transmission III. Considerations regarding
      regulatory and policy pathways.
AB  - Vector control is a task previously relegated to products that (a) kill the
      mosquitoes directly at different stages (insecticides, larvicides, baited traps),
      or (b) avoid/reduce human-mosquito contact (bed nets, repellents, house
      screening), thereby reducing transmission. The potential community-based
      administration of the endectocide ivermectin with the intent to kill mosquitoes
      that bite humans, and thus reduce malaria transmission, offers a novel approach
      using a well-known drug, but additional steps are required to address technical,
      regulatory and policy gaps. The proposed community administration of this drug
      presents dual novel paradigms; first, indirect impact on the community rather
      than on individuals, and second, the use of a drug for vector control. In this
      paper, the main questions related to the regulatory and policy pathways for such
      an application are identified. Succinct answers are proposed for how the
      efficacy, safety, acceptability, cost-effectiveness and programmatic suitability
      could result in regulatory approval and ultimately policy recommendations on the
      use of ivermectin as a complementary vector control tool.

PMID- 28434409
TI  - 'A very diadem of light': exhibitions in Victorian London, the Parliamentary
      light and the shaping of the Trinity House lighthouses.
AB  - In the midsummer of 1872 a lighthouse apparatus was installed in the Clock Tower
      of the House of Commons. The installation served the practical function of
      communicating at a distance when the House was sitting, but also provided a
      highly visible symbolic indication of the importance of lighthouse technology to
      national concerns. Further, the installation served as an experimental space in
      which rival technological designs, with corresponding visions for the lighthouse
      system, could compete in public. This article considers nineteenth-century
      lighthouse technology as a case study in the power and political significance of
      display. Manufacturers of lighthouse lenses, such as the firm of Chance Brothers,
      sought to manage interpretations of the lights through the framing of exhibitions
      and demonstrations; so too did scientific authorities, including Michael Faraday
      and John Tyndall, both of whom served in the role of scientific adviser to
      Trinity House, the body responsible for lighthouse management. Particularly
      notable in this process was the significance of urban, metropolitan display
      environments in shaping the development of the marine lighthouse system around
      the nation's periphery.

PMID- 28434410
TI  - DOSAGE AND DURATION OF ETANERCEPT THERAPY FOR ANKYLOSING SPONDYLITIS: A META
      ANALYSIS.
AB  - OBJECTIVES: We conducted a meta-analysis of recently published randomized
      controlled trials (RCTs) to identify the most effective and safe etanercept
      dosing regimen and duration of therapy for the treatment of patients with
      ankylosing spondylitis (AS). METHODS: We systematically reviewed PubMed, Embase,
      Cochrane Library, and Web of Science databases for RCTs. The proportion of
      patients attaining 20 percent improvement (according to the Spondyloarthritis
      International Society response criteria [ASAS 20]) was evaluated as a primary
      outcome. Secondary outcomes included 50 percent increase in the Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI 50) used for evaluating efficacy, as
      well as the BASDAI/Bath Ankylosing Spondylitis Functional Index (BASFI) scores
      and adverse events. RESULTS: ASAS 20 indicated that the efficacy of etanercept
      did not differ amongst dosing regimens (25 mg twice-weekly versus 50 mg once
      weekly: relative risk [RR], 2.18, 95 percent confidence interval [CI], 1.78-2.67
      versus RR, 2.00, 95 percent CI, 1.70-2.37). The ASAS 20 reported subgroup
      differences among treatment durations of less than 12 weeks (RR, 2.70; 95 percent
      CI, 2.09-3.49); 12 weeks (RR, 1.74; 95 percent CI, 1.37-2.22); and more than 12
      weeks (RR, 2.56; 95 percent CI, 1.88-3.48). Other outcomes included BASDAI,
      BASDAI 50, and BASFI. Drug safety differed according to the treatment regimen and
      duration. CONCLUSION: Our meta-analysis found that there was no significant
      efficacy difference between 50 mg once-weekly and 25 mg twice-weekly dosing for
      the treatment of AS, and a dosing duration of less than 12 weeks was more
      effective for treating AS patients.

PMID- 28434411
TI  - Direct and indirect resistance of sugarcane to Diatraea saccharalis induced by
      jasmonic acid.
AB  - Treating plants with synthetic jasmonic acid (JA) induces a defensive response
      similar to herbivore attack, and is a potential strategy for integrated pest
      management. Despite the importance of sugarcane, its JA-induced defences have not
      yet been studied. We investigated the effects of JA treatment on the direct and
      indirect resistance of sugarcane to the key-pest and specialist herbivore
      Diatraea saccharalis and the generalist Spodoptera frugiperda. Indirect defences
      were examined by testing the attraction of Cotesia flavipes, a sugarcane-borer
      parasitoid, to JA-induced volatile. The results showed that JA-treated sugarcane
      did not affect the weight gain of the two larvae. However, in dual-choice assays,
      both species preferred to feed on mock rather than JA-treated plants. Leaf
      colorimetric analyses showed that visual cues are unlikely to be involved in
      larval preference, whereas results from olfactometric assays revealed that D.
      saccharalis preferred JA-induced over mock plant volatiles. After 48 h of
      treatment, JA-treated plants emitted a volatile blend attractive to C. flavipes,
      comprised mainly of sesquiterpenes. However, the parasitoid did not discriminate
      JA-treated from host-damaged plant volatiles. When the wasps were given a choice
      between JA-treated and JA-treated + host-damaged plants, they preferred the
      latter, which emitted a more complex blend, suggesting that JA treatment likely
      does not hamper host-finding. We concluded that JA induces the emission of
      volatiles that are attractive to the sugarcane borer parasitoid, as well as an
      antixenosis type of resistance in sugarcane against the two pests, although
      neither volatiles nor visual cues alone are involved in the underlying mechanism.

PMID- 28434412
TI  - Molecular characterization and transcriptional analysis of the female-enriched
      chondroitin proteoglycan 2 of Toxocara canis.
AB  - Toxocara canis is an important but neglected zoonotic parasite, and is the
      causative agent of human toxocariasis. Chondroitin proteoglycans are biological
      macromolecules, widely distributed in extracellular matrices, with a great
      diversity of functions in mammals. However, there is limited information
      regarding chondroitin proteoglycans in nematode parasites. In the present study,
      a female-enriched chondroitin proteoglycan 2 gene of T. canis (Tc-cpg-2) was
      cloned and characterized. Quantitative real-time polymerase chain reaction (qRT
      PCR) was employed to measure the transcription levels of Tc-cpg-2 among tissues
      of male and female adult worms. A 485-amino-acid (aa) polypeptide was predicted
      from a continuous 1458-nuleotide open reading frame and designated as TcCPG2,
      which contains a 21-aa signal peptide. Conserved domain searching indicated three
      chitin-binding peritrophin-A (CBM_14) domains in the amino acid sequence of
      TcCPG2. Multiple alignment with the inferred amino acid sequences of
      Caenorhabditis elegans and Ascaris suum showed that CBM_14 domains were well
      conserved among these species. Phylogenetic analysis suggested that TcCPG2 was
      closely related to the sequence of chondroitin proteoglycan 2 of A. suum.
      Interestingly, a high level of Tc-cpg-2 was detected in female germline tissues,
      particularly in the oviduct, suggesting potential roles of this gene in
      reproduction (e.g. oogenesis and embryogenesis) of adult T. canis. The functional
      roles of Tc-cpg-2 in reproduction and development in this parasite and related
      parasitic nematodes warrant further functional studies.

PMID- 28434413
TI  - DRUG EVALUATION AND DECISION MAKING IN CATALONIA: DEVELOPMENT AND VALIDATION OF A
      METHODOLOGICAL FRAMEWORK BASED ON MULTI-CRITERIA DECISION ANALYSIS (MCDA) FOR
      ORPHAN DRUGS.
AB  - OBJECTIVES: The aim of this study was to adapt and assess the value of a Multi
      Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of Orphan
      drugs in Catalonia (Catalan Health Service). METHODS: The standard evaluation and
      decision-making procedures of CatSalut were compared with the EVIDEM methodology
      and contents. The EVIDEM framework was adapted to the Catalan context, focusing
      on the evaluation of Orphan drugs (PASFTAC program), during a Workshop with
      sixteen PASFTAC members. The criteria weighting was done using two different
      techniques (nonhierarchical and hierarchical). Reliability was assessed by re
      test. RESULTS: The EVIDEM framework and methodology was found useful and feasible
      for Orphan drugs evaluation and decision making in Catalonia. All the criteria
      considered for the development of the CatSalut Technical Reports and decision
      making were considered in the framework. Nevertheless, the framework could
      improve the reporting of some of these criteria (i.e., "unmet needs" or
      "nonmedical costs"). Some Contextual criteria were removed (i.e., "Mandate and
      scope of healthcare system", "Environmental impact") or adapted ("population
      priorities and access") for CatSalut purposes. Independently of the weighting
      technique considered, the most important evaluation criteria identified for
      orphan drugs were: "disease severity", "unmet needs" and "comparative
      effectiveness", while the "size of the population" had the lowest relevance for
      decision making. Test-retest analysis showed weight consistency among techniques,
      supporting reliability overtime. CONCLUSIONS: MCDA (EVIDEM framework) could be a
      useful tool to complement the current evaluation methods of CatSalut,
      contributing to standardization and pragmatism, providing a method to tackle
      ethical dilemmas and facilitating discussions related to decision making.

PMID- 28434414
TI  - HEALTH TECHNOLOGY ASSESSMENT OF PUBLIC HEALTH INTERVENTIONS: A SYNTHESIS OF
      METHODOLOGICAL GUIDANCE.
AB  - OBJECTIVES: The evaluation of public health interventions poses some challenges.
      As a consequence, health technology assessment (HTA) methods for public health
      interventions (PHI) have to be adapted. This study aimed to summarize the
      available guidance on methods for HTA of PHI. METHODS: We systematically searched
      for methodological guidance on HTA of PHIs. Our focus was on research synthesis
      methods to evaluate effectiveness. Relevant information was synthesized
      narratively in a standardized way. RESULTS: Only four guidance documents were
      identified specifically for HTAs of PHI. The approaches used for HTAs of PHIs are
      broader and more flexible than those for medical interventions. For this reason,
      there is a tendency to identify the intervention components and context factors
      that influence the effectiveness and transferability of an intervention rather
      than to assess its effectiveness in general. The details in the guidance vary
      without justification. Unjustified heterogeneity between the different guidance
      approaches is most pronounced for quality assessment, assessment of
      applicability, and methods to integrate qualitative and quantitative evidence.
      Descriptions for the assessment of integrity, heterogeneity, sustainability,
      context factors, and applicability are often vague. CONCLUSIONS: The
      heterogeneity in approaches indicates that there is currently no consensus on
      methods to deal with the challenges of the PHI evaluations. A possible
      explanation for this may be that the methods are not sufficiently developed, and
      advantages and disadvantages of a certain method in relation to the research
      question (e.g., broad/focused) have not yet been sufficiently evaluated.

PMID- 28434415
TI  - Does the Incredible Years reduce child externalizing problems through improved
      parenting? The role of child negative affectivity and serotonin transporter
      linked polymorphic region (5-HTTLPR) genotype.
AB  - In a randomized controlled trial, the Observational Randomized Controlled Trial
      of Childhood Differential Susceptibility (ORCHIDS study), we tested whether
      observed parental affect and observed and reported parenting behavior are
      mechanisms of change underlying the effects of the behavioral parent training
      program the Incredible Years (IY). Furthermore, we tested whether some children
      are more susceptible to these change mechanisms because of their temperamental
      negative affectivity and/or serotonin transporter linked polymorphic region (5
      HTTLPR) genotype. Participants were 387 Dutch children between 4 and 8 years of
      age (M age = 6.31, SD = 1.33; 55.3% boys) and their parents. Results showed that
      although IY was successful in improving parenting behavior and increasing
      parental positive affect, these effects did not explain the significant decreases
      in child externalizing problems. We therefore found no evidence for changes in
      parenting behavior or parental affect being the putative mechanisms of IY
      effectiveness. Furthermore, intervention effects on child externalizing behavior
      were not moderated by child negative affectivity or 5-HTTLPR genotype. However,
      child 5-HTTLPR genotype did moderate intervention effects on negative parenting
      behavior. This suggests that in research on behavioral parent training programs,
      "what works for which parents" might also be an important question.

PMID- 28434416
TI  - INTRODUCTION OF HEALTH TECHNOLOGY ASSESSMENT FOR MEDICINES IN SLOVAKIA.
AB  - OBJECTIVES: The aim of our study was to describe approaches to health technology
      assessment (HTA) for medicines in the Slovak healthcare system and the related
      decision-making processes concerning reimbursement for medicines. METHODS:
      Analysis of the Slovak legislative framework related to HTA and the reimbursement
      process for medicines was performed. Additionally, current practices of the
      Working Group for Pharmacoeconomics, Clinical Outcomes and Health Technology
      Assessment of the Slovak Ministry of Health were evaluated. RESULTS: In Slovakia,
      there is always at least one treatment available in each determined therapeutic
      class with no co-payment. HTA is becoming an established method for the
      evaluation of cost-effectiveness of medicines in Slovak healthcare policy. The
      majority of decision makers within Slovakia support the idea of increased use of
      and the quality and efficiency of HTA methods. However, it is crucial to overcome
      several practical barriers to facilitate progress in the field of HTA in the
      Slovak Republic. CONCLUSIONS: It can be seen that participation within the
      European Network for Health Technology Assessment (EUnetHTA JA 2 and EUnetHTA JA
      3 projects) has significantly improved the quality of the process of HTA in
      Slovakia. Further legislative activities in this field are required due to the
      approved strategy for European Union cooperation on HTA.

PMID- 28434417
TI  - HEALTH TECHNOLOGY ASSESSMENT IN CENTRAL-EASTERN AND SOUTH EUROPE COUNTRIES:
      BOSNIA AND HERZEGOVINA.
AB  - OBJECTIVES: The aim of this study was to describe the healthcare system and
      health financing in Bosnia and Herzegovina and recent trends in health technology
      assessment (HTA) placement in the system. METHODS: A short review of PubMed
      published literature has been conducted using key words related to reimbursement,
      HTA, and health policy. We also revised legislation in Bosnia and Herzegovina
      published in Official Gazettes related to healthcare financing and organization.
      RESULTS: A deecentralized system in Bosnia and Herzegovina led to high
      differences in health policy. HTA has been recognized in legislation in Bosnia
      and Herzegovina, but it still has not been introduced in practice in full
      capacity. A small number of publications are found in PubMed treating these
      issues, but generally the problem of introduction of HTA in Bosnia and
      Herzegovina is lack of experts, as well as the political environment and
      education in this field. CONCLUSIONS: HTA in the Federation of Bosnia and
      Herzegovina and the Republic of Srpska has a short history because of a huge
      political impact in the decision-making process, decentralized system, and
      multiple decision makers in these regions. Challenges remain in assessments, in
      development of more transparent approaches in different areas of the health
      system in these regions, and in consistent application of appropriate standards
      especially in education of professionals who will provide establishment of HTA in
      the health system of The Federation of Bosnia and Herzegovina and the Republic of
      Srpska.

PMID- 28434418
TI  - Beliefs and attitudes towards the influenza vaccine in high-risk individuals.
AB  - Societal and economic impact of influenza is mainly due to influenza infection of
      specific groups, who are at higher risk of health complications leading up to
      hospitalisation or death. In this study we applied the health belief model (HBM)
      to evaluate beliefs and attitudes towards influenza disease and vaccine in
      community-dwelling high-risk individuals (aged 65 or more or having a chronic
      disease). We conducted a mixed-method study using data collected through a
      telephone survey of a household unit sample. We used thematic analysis to map
      responses to HBM dimensions and Poisson regression to model vaccine non-uptake
      prevalence. The main self-reported reason not to take the vaccine referred to the
      susceptibility dimension: 'considering oneself to be a healthy person' (29.8%,
      (95% confidence interval (CI) 22.1-38.7)). Bad experiences after vaccination -
      barriers dimension - were also commonly reported (17.0%, (95% CI 10.8-23.8)).
      Vaccine non-uptake prevalence was 22% higher in those who did not consider
      themselves susceptible to contract flu (Prevalence Ratio (PR) = 1.22, (95% CI 1.0
      1.5)) and 18% lower in those who did not consider that the vaccine causes flu
      symptoms (PR = 0.82, (95% CI 0.68-0.99)). Results suggest that high-risk
      individuals do not think of themselves susceptible to influenza infection and
      fear adverse events following immunisation.

PMID- 28434419
TI  - Factors of nocturnal sleep and daytime nap durations in community-dwelling
      elderly: a longitudinal population-based study.
AB  - BACKGROUND: Durations of nocturnal sleep and daytime nap influence the well-being
      of older adults. It is thus essential to understand their determinants. However,
      much previous research did not assess sleep duration and nap duration
      individually, and longitudinal data is lacking. This study aimed at examining the
      impact of demographic, psychosocial, and health factors, including ethnicity,
      social networks outside the household, smoking and physical exercise on sleep
      duration and nap duration among community-dwelling elderly. METHODS: Our study
      involved over 2,600 older adults (>=60 years) from a longitudinal, nationally
      representative survey - the Panel on Health and Ageing of Singaporean Elderly.
      Sleep and nap durations at Time 2 (two years later) were regressed on predictors
      measured at Time 1. RESULTS: Time 2 short nocturnal sleep duration was predicted
      by Malay ethnicity (relative to Chinese and Indian), older age, lower education
      level, more depressive symptoms, and obesity, whereas future long nocturnal sleep
      duration was predicted by weaker social networks, older age, and more chronic
      diseases. Furthermore, smoking, obesity, Malay or Indian (relative to Chinese),
      older age, male gender, and cognitive impairment predicted longer daytime nap
      duration in the future. CONCLUSIONS: Older adults' nocturnal sleep and daytime
      nap durations may be affected by different demographic, psychosocial, and health
      factors. Thus, it is important to differentiate these two attributes in this age
      group.

PMID- 28434421
TI  - Galileo's legacy: a critical edition and translation of the manuscript of
      Vincenzo Viviani's Grati Animi Monumenta.
AB  - Having been found 'vehemently suspected of heresy' by the Holy Office in 1633, at
      the time of his death (1642) Galileo's remains were laid to rest in the tiny
      vestry of a lateral chapel of the Santa Croce Basilica, Florence. Throughout his
      life, Vincenzo Viviani, Galileo's last disciple, struggled to have his master's
      name rehabilitated and his banned works reprinted, as well as a proper funeral
      monument erected. He did not live to see all this come true, but his efforts
      triggered a mechanism that eventually led to the fulfilment of his wishes. A key
      element of his project was the transformation of the facade of his palace into a
      private (but publicly rendered) tribute to Galileo, with two long inscriptions
      celebrating Galileo's achievements and calling Florence's attention to the need
      to pay a proper tribute to him. Shortly afterwards, he revised the text and
      circulated it in print. This article presents the first critical edition and
      annotated translation of Viviani's original manuscript, long thought to be lost,
      and describes its role in Viviani's lifelong struggle for Galileo's intellectual
      legacy, as well as its impact on future historiography.

PMID- 28434420
TI  - Environmental sampling coupled with real-time PCR and genotyping to investigate
      the source of a Q fever outbreak in a work setting.
AB  - A Q fever outbreak was declared in February 2016 in a company that manufactures
      hoists and chains and therefore with no apparent occupational-associated risk.
      Coxiella burnetii infection was diagnosed by serology in eight of the 29 workers
      of the company; seven of them had fever or flu-like signs and five had pneumonia,
      one requiring hospitalisation. A further case of C. burnetii pneumonia was
      diagnosed in a local resident. Real-time PCR (RTi-PCR) showed a widespread
      distribution of C. burnetii DNA in dust samples collected from the plant
      facilities, thus confirming the exposure of workers to the infection inside the
      factory. Epidemiological investigations identified a goat flock with high C.
      burnetii seroprevalence and active shedding which was owned and managed by one of
      the workers of the company as possible source of infection. Genotyping by
      multispacer sequence typing (MST) and a 10-loci single-nucleotide polymorphism
      (SNP) discrimination using RTi-PCR identified the same genotype (MST18 and SNP
      type 8, respectively) in the farm and the factory. These results confirmed the
      link between the goat farm and the outbreak and allowed the identification of the
      source of infection. The circumstances and possible vehicles for the bacteria
      entering the factory are discussed.

PMID- 28434422
TI  - PATIENT WEB PORTALS AND PATIENT-PROVIDER RELATIONSHIPS: A SUMMARY PERSPECTIVE.
AB  - OBJECTIVES: Patient Web portals (PWPs) have been gaining traction as a means to
      collect patient-reported outcomes and maintain quality patient care between
      office visits. PWPs have the potential to impact patient-provider relationships
      by rendering additional channels for communication outside of clinic visits and
      could help in the management of common chronic medical conditions. Studies
      documenting their effect in primary care settings are limited. This perspective
      aims to summarize the benefits and drawbacks of using PWPs in the management of
      chronic conditions, such as diabetes mellitus, hypertension, and asthma, focusing
      on communication, disease management, compliance, potential barriers, and the
      impact on patient-provider dynamic. After a review of these topics, we present
      potential future directions. METHODS: We conducted an exploratory PubMed search
      of the literature published from inception through December 2015, and focused our
      subsequent searches specifically to assess benefits and drawbacks of using PWPs
      in the management of diabetes mellitus, hypertension, and asthma. RESULTS: Our
      search revealed several potential benefits of PWP implementation in the
      management of chronic conditions with regards to patient-provider relationships,
      such as improved communication, disease management, and compliance. We also noted
      drawbacks such as potentially unreliable reporting, barriers to use, and
      increased workload. CONCLUSIONS: PWPs offer opportunities for patients to report
      symptoms and outcomes in a timely manner and allow for secure online
      communication with providers. Despite the drawbacks noted, the overall benefits
      from successful PWP implementation could improve patient-provider relationships
      and help in the management of chronic conditions, such as diabetes mellitus,
      hypertension, and asthma.

PMID- 28434423
TI  - CURRENT IMPLEMENTATION OF HEALTH TECHNOLOGY ASSESSMENT IN HEALTHCARE SYSTEM IN
      SLOVENIA.
AB  - OBJECTIVES: The objective of this study was to analyze and present the current
      state of the implementation of health technology assessment (HTA) in Slovenia,
      identify its advantages and challenges, as well as potential improvements and
      developments. METHODS: The HTA structure and processes were analyzed and
      comprehensively described according to relevant literature, official documents,
      and experiences of the author. RESULTS: The important steps in the development
      and implementation of an HTA system are presented through eight key elements:
      capacity building; HTA funding; HTA legislation and organizational structure; the
      scope of HTA implementation; decision criteria; quality, timelines, and
      transparency of HTA implementation; use of local data; and international
      collaboration. Based on the current situation, possible further developments are
      presented. CONCLUSIONS: Currently, there is no systematic HTA in Slovenia;
      however, some basic use of HTA principles can be found in the decision making.
      The biggest deficiency in the HTA field is the lack of knowledge and systematic
      implementation. Legislation and guidelines for study appraisals are needed at
      decision-making levels. HTA principles across health technologies need to be
      unified along with a central HTA coordination office being set up to lead and
      establish priorities for HTA work.

PMID- 28434424
TI  - An investigation of residential facility staff usage of touchscreen technology.
AB  - Older adults may become more familiar and interested in using touchscreen
      technology (TT). TT can be used to engage older adults living in residential aged
      care facilities (RACFs) and staff there can play an important role in supporting
      residents to use TT. However, before these are introduced, it is crucial to
      investigate their opinions in using TT with residents. A questionnaire based on
      the Technology Acceptance Model was administered to assess staff usage and
      confidence in using TT, their perceptions in TT ease-of-use and usefulness in
      helping them care for their residents. Perhaps unsurprisingly, results found that
      respondents were familiar using TT. More importantly, staff reported that they
      were interested in engaging residents with TT and nominated different training
      methods to support them such as group in-services. This project provides
      information about staff experience and acceptance of the use of TT for residents
      in RACFs.

PMID- 28434425
TI  - Augmented Reality in Neurosurgery: A Review of Current Concepts and Emerging
      Applications.
AB  - Augmented reality (AR) superimposes computer-generated virtual objects onto the
      user's view of the real world. Among medical disciplines, neurosurgery has long
      been at the forefront of image-guided surgery, and it continues to push the
      frontiers of AR technology in the operating room. In this systematic review, we
      explore the history of AR in neurosurgery and examine the literature on current
      neurosurgical applications of AR. Significant challenges to surgical AR exist,
      including compounded sources of registration error, impaired depth perception,
      visual and tactile temporal asynchrony, and operator inattentional blindness.
      Nevertheless, the ability to accurately display multiple three-dimensional
      datasets congruently over the area where they are most useful, coupled with
      future advances in imaging, registration, display technology, and robotic
      actuation, portend a promising role for AR in the neurosurgical operating room.

PMID- 28434426
TI  - ATTITUDES OF ORTHOPEDIC SPECIALISTS TOWARD EFFECTS OF MEDICAL DEVICE PURCHASING.
AB  - OBJECTIVES: The aim of this study was to assess viewpoints of end-users
      concerning the purchasing process of high-risk medical devices and to discuss the
      relevance of health technology assessments (HTAs) at the hospital level and other
      potential areas for improvement of purchasing processes. METHODS: We used a cross
      sectional study and assessed the attitudes and thoughts of orthopedic
      specialists. The study took place between June and October 2015 in Mexico.
      RESULTS: We collected data from 187 orthopedic surgeons. Involvement of
      orthopedic specialists in purchasing was reported by 86 percent. However,
      clinical practice was perceived as negatively influenced by purchasing outcomes
      by 92 percent. The problems were described as: material failure; effectiveness of
      medical devices; obsolete medical device technology; incomplete provision of
      implant / instrument sets; delayed provision of implants and instruments.
      CONCLUSIONS: To prevent sub-standard outcomes of purchasing decisions, this study
      and the current literature suggest that technologies should be assessed during
      the purchasing process, end-users should be adequately involved, and decisions
      should be based on multiple criteria including clinical impact in the short-term
      (e.g., primary stability of implant) and long-term (e.g., survival of implant).
      The focus on Mexico is particularly novel and provides insights into a health
      system where HTA is mainly present at the macro level and can be used for the
      listing of medical device technologies in the standard list. This study concludes
      that Mexican stakeholders of the purchasing process underestimate the
      contribution of HTAs at the level of purchasing decisions. HTA in Mexico has
      improved over the past years but still requires more advancement.

PMID- 28434428
TI  - Local Response of Sialoliths to Lithotripsy: Cues on Fragmentation Outcome.
AB  - Lithotripsy methods show relatively low efficiency in the fragmentation of
      sialoliths compared with the success rates achieved in the destruction of renal
      calculi. However, the information available on the mechanical behavior of
      sialoliths is limited and their apparently tougher response is not fully
      understood. This work evaluates the hardness and Young's modulus of sialoliths at
      different scales and analyzes specific damage patterns induced in these calcified
      structures by ultrasonic vibrations, pneumoballistic impacts, shock waves, and
      laser ablation. A clear correlation between local mechanical properties and
      ultrastructure/chemistry has been established: sialoliths are composite materials
      consisting of hard and soft components of mineralized and organic nature,
      respectively. Ultrasonic and pneumoballistic reverberations damage preferentially
      highly mineralized regions, leaving relatively unaffected the surrounding organic
      matter. In contrast, shock waves leach the organic component and lead to erosion
      of the overall structure. Laser ablation destroys homogeneously the irradiated
      zones regardless of the mineralized/organic nature of the underlying
      ultrastructure; however, damage is less extensive than with mechanical methods.
      Overall, the present results show that composition and internal structure are key
      features behind sialoliths' comminution behavior and that the organic matter
      contributes to reduce the therapeutic efficiency of lithotripsy methods.

PMID- 28434427
TI  - Prenatal fish oil supplementation and early childhood development in the Upstate
      KIDS Study.
AB  - Fish oil contains omega-3 fatty acids, which play a vital role in fetal growth
      and development. In utero exposure to omega-3 fatty acids is exclusively
      dependent on maternal nutrition. Previous studies have suggested that prenatal
      fish oil supplementation has positive impacts on child neurodevelopment later in
      life. This study examines the associations between fish oil supplementation both
      before pregnancy and throughout pregnancy and subsequent child development.
      Mother-child pairs from the Upstate KIDS Study, a birth cohort consisting of
      children born between 2008 and 2010, were included. Self-reported prenatal fish
      oil supplementation data were available for 5845 children (3807 singletons and
      2038 twins). At multiple time points, from 4 months to 3 years of age, child
      development was reported by the parents on the Ages and Stages Questionnaire
      (ASQ). Five developmental domains were assessed: fine motor, gross motor,
      communication, personal-social functioning and problem solving. Generalized
      linear mixed models were used to estimate odds ratios (OR) while adjusting for
      covariates. Primary analyses showed that the risk of failing the ASQ problem
      solving domain was significantly lower among children of women who took fish oil
      before pregnancy (OR 0.40, 95% confidence intervals (CI) 0.18-0.89) and during
      pregnancy (OR 0.43, 95% CI 0.22-0.83). Gender interaction was not statistically
      significant, although stratified results indicated stronger associations among
      girls. Similarly, associations were primarily among singletons. Prenatal fish oil
      supplementation may be beneficial in regards to neurodevelopment. Specifically,
      it is associated with a lower risk of failing the problem-solving domain up to 3
      years of age.

PMID- 28434430
TI  - Studies of the Seasonal Pattern of Multiple Maternities.
AB  - The seasonality of population data has been of great interest in demographic
      studies. When seasonality is analyzed, the population at risk plays a central
      role. In a study of the monthly number of births and deaths, the population at
      risk is the product of the size of the population and the length of the month.
      Usually, the population can be assumed to be constant, and consequently, the
      population at risk is proportional to the length of the month. Hence, the number
      of cases per day has to be analyzed. If one studies the seasonal variation in
      twin or multiple maternities, the population at risk is the total number of
      monthly confinements, and the study should be based on the rates of the multiple
      maternities. Consequently, if one considers monthly twinning rates, the monthly
      number of birth data is eliminated and one obtains an unaffected seasonality
      measure of the twin maternities. The strength of the seasonality is measured by a
      chi-squared test or by the standard deviation. When seasonal models are applied,
      one must pay special attention to how well the model fits the data. If the
      goodness of fit is poor, it can erroneously result in a statement that the
      seasonality is slight, although the observed seasonal fluctuations are marked.

PMID- 28434429
TI  - Association between Sleep Disordered Breathing and Nighttime Driving Performance
      in Mild Cognitive Impairment.
AB  - OBJECTIVES: The effect of sleep disordered breathing (SDB) on driving performance
      in older adults has not been extensively investigated, especially in those with
      mild cognitive impairment (MCI). The aim of this study was to examine the
      relationship between severity measures of SDB and a simulated driving task in
      older adults with and without MCI. METHODS: Nineteen older adults (age >=50)
      meeting criteria for MCI and 23 age-matched cognitively intact controls underwent
      neuropsychological assessment and a driving simulator task in the evening before
      a diagnostic sleep study. RESULTS: There were no differences in driving simulator
      performance or SDB severity between the two groups. In patients with MCI, a
      higher oxygen desaturation index (ODI) was associated with an increased number of
      crashes on the simulator task, as well as other driving parameters such as
      steering and speed deviation. Poorer driving performance was also associated with
      poorer executive functioning (set-shifting) but the relationship between ODI and
      crashes was independent of executive ability. CONCLUSIONS: While driving ability
      did not differ between older adults with and without MCI, oxygen saturation dips
      in MCI were related to worse driving performance. These results suggest that
      decreased brain integrity may render those with SDB particularly vulnerable to
      driving accidents. In older adults, both cognition and SDB need to be considered
      concurrently in relation to driving ability. (JINS, 2017, 23, 502-510).

PMID- 28434431
TI  - A concept analysis in relation to the cultural competency of the palliative care
      workforce in meeting the needs of young people from South Asian cultures.
AB  - : ABSTRACTObjective:Our aims were to report an analysis of the concept of
      cultural competency and to explore how the cultural competency of the palliative
      care workforce impacts the holistic care of young people with palliative care
      needs from South Asian cultures. METHOD: Using keywords, we searched the online
      databases MEDLINE, CINAHL, ScienceDirect, and PubMed from January of 1990 through
      to December of 2016. Some 1543 articles were retrieved, and inclusion and
      exclusion criteria were applied. A total of 38 papers were included in the
      concept analysis. The data were analyzed using Coad's (2002) adapted framework
      based on Rodgers's (1989) evolutionary concept analysis, focusing on the
      attributes, antecedents, consequences, and related terms in relation to
      culturally competent care. A model case of culturally competent care was also
      constructed. RESULTS: The literature provides evidence that the concept of
      culturally competent care is a complex one, which is often expressed ambiguously.
      In addition, there is a paucity of research that involves service users as
      experts in defining their own needs and assessing their experiences related to
      cultural care. SIGNIFICANCE OF RESULTS: Cultural care should be integral to
      holistic patient care, irrespective of a person's race or ethnicity. There is an
      urgent need to involve young BAME patients with palliative care needs and their
      families in the development of a robust tool to assess cultural competency in
      clinical practice.

PMID- 28434432
TI  - Pattern Center and Distortion Determined from Faint, Diffuse Electron Diffraction
      Rings from Amorphous Materials.
AB  - Diffuse rings from amorphous materials sit on a steep background resulting in a
      monotonically decreasing intensity over scattering vector length, frequently with
      no clear local maximum that could be used to determine the center of the ring.
      The novelty of the method reported here is that it successful processes such weak
      patterns. It is based on separating the angular dependence of the positions of
      the maxima on the azimuthal angle in the measured two-dimensional pattern for a
      manually preselected peak. Both pattern center and elliptical distortion are
      simultaneously refined from this angular dependence. Both steps are based on
      nonlinear least square fitting, using the Levenberg-Marquardt method. It can be
      successfully applied to any amorphous patterns provided they were recorded with
      experimental conditions that facilitate dividing them into sectors with
      acceptable statistics. Patterns with the center shifted to the camera corner
      (recording a quadrant of a ring) can also be reliably evaluated, keeping
      precalibrated values of the elliptical distortion fixed during the fit. Finally,
      the limited number of counts in any pattern is overcome by cumulating many
      patterns (from equivalent areas) into a single pattern. Eliminating false effects
      is facilitated by masking out unwanted parts of any recorded pattern from
      processing.

PMID- 28434433
TI  - OVERVIEW ON THE CURRENT IMPLEMENTATION OF HEALTH TECHNOLOGY ASSESSMENT IN THE
      HEALTHCARE SYSTEM IN HUNGARY.
AB  - OBJECTIVES: Our objectives were to assess the current implementation of health
      technology assessment (HTA) in Hungary and to identify country-specific patterns
      of challenges and potential improvements. METHODS: We applied a structure that
      can be used to create HTA implementation roadmaps to evaluate various issues
      regarding HTA implementation. A comprehensive description of the Hungarian HTA
      system is presented according to relevant literature and experiences of the
      authors. RESULTS: By investigating eight components of HTA implementation, we
      identified the most important strengths and weaknesses of the Hungarian system.
      More specifically, we were mainly focusing on the emergence of HTA capacity, the
      establishment and current role of Department of HTA, the complex process of
      decision making, the quality elements developed in the near past, and the
      activity of Hungarian experts at international collaborations. CONCLUSIONS: We
      concluded that there is a sophisticated methodological and educational basis for
      HTA in Hungary. A permanent focus on capacity building and changes to the
      reimbursement procedure can further improve transparency and the scientific basis
      of decision making in the country.

PMID- 28434434
TI  - Local Structural Damage Evaluation of a C/C-SiC Ceramic Matrix Composite.
AB  - Ceramic matrix composites (CMCs) are structural materials, which have useful
      properties that combine high strength at high temperatures with moderate
      toughness. Carbon fibers within a matrix of carbon and silicon carbide, called
      C/C-SiC, are a particular class of CMC noted for their high oxidation resistance.
      Here we use a combination of four-point bending and X-ray radiography, to study
      the mechanical failure of C/C-SiC CMCs. Correlating X-ray radiographic and
      load/displacement curve data reveals that the fiber bundles act to slow down
      crack propagation during four-point bending tests. We attribute this to the fact
      that strain energy is expended in breaking these fibers and in pulling fiber
      bundles out of the surrounding matrix material. In addition, we find that the
      local distribution and concentration of SiC plays an important role in reducing
      the toughness of the material.

PMID- 28434435
TI  - Association between burnout and cortisol secretion, perceived stress, and
      psychopathology in palliative care unit health professionals.
AB  - : ABSTRACTObjective:A high incidence of burnout has been reported in health
      professionals working in palliative care units. Our present study aims to
      determine whether there are differences in the secretion of salivary cortisol
      between palliative care unit health professionals with and without burnout, and
      to elucidate whether there is a relationship between burnout syndrome and
      perceived stress and psychopathological status in this population. METHOD: A
      total of 69 health professionals who met the inclusion criteria participated in
      our study, including physicians, nurses, and nursing assistants. Some 58 were
      women (M = 29.65 years, SD = 8.64) and 11 men (M = 35.67 years, SD = 11.90). The
      level of daily cortisol was registered in six measurements taken over the course
      of a workday. Burnout syndrome was evaluated with the Maslach Burnout Inventory
      Human Services Survey (MBI-HSS), the level of perceived stress was measured using
      the Perceived Stress Scale, and psychopathological status was gauged using the
      SCL-90-R Symptoms Inventory. RESULTS: There were statistically significant
      differences in secretion of cortisol in professionals with high scores on a
      single subscale of the MBI-HSS [F(3.5) = 2.48, p < 0.03]. This effect was
      observed 15-30 minutes after waking up (p < 0.01) and at bedtime (p < 0.06).
      Moreover, the professionals with burnout showed higher scores on the
      psychopathology and stress subscales than professionals without it. SIGNIFICANCE
      OF RESULTS: A higher score in any dimension of the burnout syndrome in palliative
      care unit health professionals seems to be related to several physiological and
      psychological parameters. These findings may be relevant for further development
      of our understanding of the relationship between levels of burnout and cortisol
      secretion in the health workers in these units.

PMID- 28434437
TI  - Sudden Unilateral Impairment of Vision.

PMID- 28434436
TI  - Treatment Options for Gout.
AB  - BACKGROUND: 1-2% of adults in Germany suffer from gout. Gout is one of the few
      rheumatological diseases that can be cured. It arises through the deposition of
      uric acid crystals in joints as a result of hyperuricemia. Painful redness and
      swelling of the affected joints are typical findings. Multiple pertinent
      guidelines and treatment recommendations have been published, but there is reason
      to believe that patients with gout are not always treated accordingly. METHODS:
      This review is based on relevant publications from the years 2000-2016 that were
      retrieved by a selective search in the Cochrane and PubMed databases. RESULTS: In
      a person with normal renal function, asymptomatic hyperuricemia is not an
      indication for treatment to lower the serum uric acid level. The drugs of first
      choice for acute gouty arthritis are nonsteroidal antiinflammatory drugs (NSAID),
      corticosteroids, and colchicine. Treatment with xanthine oxidase inhibitors (XOI)
      or uricosuric drugs is indicated for patients with a recurrent or severe course;
      the target uric acid value is <6 mg/dL. Long-term treatment should be initiated
      only after resolution of the acute attack. For patients with refractory gout,
      lesinurad (approved in February 2016) in combination with XOI is a new treatment
      option that can be considered. Comprehensive patient education and counseling is
      an important component of the treatment of patients with gout. Regular laboratory
      follow-up is necessary as well. CONCLUSION: The prevalence of gout is rising
      around the world. Patients with gout could benefit greatly from consistent
      implementation of the existing treatment guidelines and recommendations. In the
      future, controlled trials should be conducted to determine the best time to start
      treatment and the optimal target level for the serum uric acid concentration in
      terms of a risk/benefit analysis.

PMID- 28434438
TI  - Effects Are not Clear.

PMID- 28434439
TI  - In Reply.

PMID- 28434440
TI  - Avoiding Errors in Chemotherapy.

PMID- 28434441
TI  - In Reply.

PMID- 28434442
TI  - A Right Atrial Mass in a Woman With Newly Diagnosed Breast Cancer.

PMID- 28434444
TI  - Mark E. Josephson, MD, Personal Remembrances.

PMID- 28434443
TI  - Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is associated with a
      mortality of more than 30%. Only about 30% of patients with SAB recover
      sufficiently to return to independent living. METHODS: This article is based on a
      selective review of pertinent literature retrieved by a PubMed search. RESULTS:
      Acute, severe headache, typically described as the worst headache of the
      patient's life, and meningismus are the characteristic manifestations of SAH.
      Computed tomog raphy (CT) reveals blood in the basal cisterns in the first 12
      hours after SAH with approximately 95% sensitivity and specificity. If no blood
      is seen on CT, a lumbar puncture must be performed to confirm or rule out the
      diagnosis of SAH. All patients need intensive care so that rebleeding can be
      avoided and the sequelae of the initial bleed can be minimized. The immediate
      transfer of patients with acute SAH to a specialized center is crucially
      important for their outcome. In such centers, cerebral aneurysms can be excluded
      from the circulation either with an interventional endovascular procedure
      (coiling) or by microneurosurgery (clipping). CONCLUSION: SAH is a life
      threatening condition that requires immediate diagnosis, transfer to a
      neurovascular center, and treatment without delay.

PMID- 28434445
TI  - Leadership Letter.

PMID- 28434446
TI  - Revisiting pulmonary vein isolation alone for persistent atrial fibrillation: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Early studies demonstrated relatively low success rates for pulmonary
      vein isolation (PVI) alone in patients with persistent atrial fibrillation
      (PeAF). However, the advent of new technologies and the observation that
      additional substrate ablation does not improve outcomes have created a new focus
      on PVI alone for treatment of PeAF. OBJECTIVE: The purpose of this study was to
      systematically review the recent medical literature to determine current medium
      term outcomes when a PVI-only approach is used for PeAF. METHODS: An electronic
      database search (MEDLINE, Embase, Web of Science, PubMed, Cochrane) was performed
      in August 2016. Only studies of PeAF patients undergoing a "PVI only" ablation
      strategy using contemporary radiofrequency (RF) technology or second-generation
      cryoballoon (CB2) were included. A random-effects model was used to assess the
      primary outcome of pooled single-procedure 12-month arrhythmia-free survival.
      Predictors of recurrence were also examined and a meta-analysis performed if >=4
      studies examined the parameter. RESULTS: Fourteen studies of 956 patients, of
      whom 45.2% underwent PVI only with RF and 54.8% with CB2, were included. Pooled
      single-procedure 12-month arrhythmia-free survival was 66.7% (95% confidence
      interval [CI] 60.8%-72.2%), with the majority of patients (80.5%) off
      antiarrhythmic drugs. Complication rates were very low, with cardiac tamponade
      occurring in 5 patients (0.6%) and persistent phrenic nerve palsy in 5 CB2
      patients (0.9% of CB2). Blanking period recurrence (hazard ratio 4.68, 95% CI
      1.70-12.9) was the only significant predictor of recurrence. CONCLUSION: A PVI
      only strategy in PeAF patients with a low prevalence of structural heart disease
      using contemporary technology yields excellent outcomes comparable to those for
      paroxysmal AF ablation.

PMID- 28434447
TI  - Could less be more in catheter ablation for persistent atrial fibrillation?
      Pulmonary vein isolation reconsidered.

PMID- 28434448
TI  - Gastric hypomotility after second-generation cryoballoon ablation-Unrecognized
      silent nerve injury after cryoballoon ablation.
AB  - BACKGROUND: Few data are available on gastric hypomotility (GH) after cryoballoon
      pulmonary vein isolation. Also, the use of esophageal temperature monitoring for
      the prevention of endoscopically detected esophageal lesions (EDELs) is not well
      established. OBJECTIVE: The purpose of this study was to investigate GH and the
      impact of an esophageal probe on EDELs during second-generation cryoballoon
      ablation. METHODS: One hundred four patients with paroxysmal atrial fibrillation
      undergoing second-generation cryoballoon ablation under conscious sedation
      followed by esophagogastroscopy were prospectively included. Temperature probes
      were used in the first 40 (38.5%) patients, but not in the latter 64 (61.5%).
      Pulmonary vein isolation was performed with one 28-mm balloon using single 3
      minute freeze techniques. RESULTS: Clinical and procedural characteristics were
      similar between the groups. Esophagogastroscopy 1.4 +/- 0.5 days postablation
      demonstrated GH and EDELs in 18 (17.3%) and 9 (8.7%) patients. The incidence of
      GH was similar (7 of 40 vs 11 of 64; P = .967) between the groups, while that of
      EDELs was significantly higher in the former than in the latter group (8 of 40 vs
      1 of 64; P < .0001). In multivariate analyses, the esophagus-right inferior
      pulmonary vein ostium distance (hazard ratio 0.870; 95% confidence interval 0.798
      0.948; P = .002) was the sole predictor of GH, and the optimal cutoff for the
      prediction was 18.2 mm (sensitivity 88.1%; specificity 77.8%). The use of
      esophageal probes was the sole predictor of EDELs (hazard ratio 15.750; 95%
      confidence interval 1.887-131.471; P = .011). All collateral damage was
      asymptomatic and healed on repeat esophagogastroscopy at a mean of 2 +/- 1 months
      postprocedure. CONCLUSION: Second-generation cryoballoon ablation is associated
      with an increased incidence of silent periesophageal nerve injury even using
      short freeze times, and anatomical information aids identifying high-risk
      populations. The use of esophageal probes increases the risk of EDELs.

PMID- 28434450
TI  - High-degree atrioventricular block in a 77-year-old man.

PMID- 28434449
TI  - Electrical superior vena cava isolation using a novel pace-and-ablate technique
      under diaphragmatic electromyography monitoring.
AB  - BACKGROUND: Diaphragmatic compound motor action potential (CMAP) amplitude
      monitoring is a standard technique to anticipate phrenic nerve injury during
      cryoballoon ablation. OBJECTIVE: The purpose of this study was to evaluate the
      feasibility of a novel superior vena cava isolation (SVCI) technique using
      simultaneous pacing and ablation through the tip of a single mapping/ablation
      catheter. METHODS: Fifty-four patients with atrial fibrillation were included.
      Radiofrequency energy was delivered point by point uniformly for 20 seconds with
      a power of 20 W until achieving SVCI. Diaphragmatic CMAPs were obtained from
      modified surface electrodes by high-output pacing from the mapping/ablation
      catheter throughout the procedure (pace-and-ablate group). Applications were
      interrupted if CMAP amplitudes significantly decreased without fluoroscopy. The
      data were compared with those of the 54 patients undergoing conventional SVCI
      (conventional group). RESULTS: Successful SVCI procedures were achieved in all
      with a mean of 10.3 +/- 2.9 applications. In total, among 559 ablation sites,
      CMAPs were recorded at 95 (17.0%) with baseline amplitudes of 0.45 +/- 0.23 mV.
      In 10 patients (18.5%), isolation was achieved without any radiofrequency
      deliveries at CMAP-recorded sites. Among the 95 applications, 6 (6.3%) were
      interrupted because of CMAP amplitude reductions. At the remaining 88 sites, 20
      second radiofrequency applications were delivered without any amplitude decrease
      (from 0.45 +/- 0.21 to 0.46 +/- 0.23 mV; P = .885). Phrenic nerve injury occurred
      in 1 patient in the pace-and-ablate group, which recovered 3 months later, and in
      3 conventional group patients, of whom 1 recovered 1 month later (P = .308). The
      total procedure time tended to be shorter (14.5 +/- 6.3 minutes vs 16.7 +/- 9.2
      minutes; P = .153) and fluoroscopy time significantly shorter (3.9 +/- 3.0
      minutes vs 6.7 +/- 5.7 minutes, P = .002) in the pace-and-ablate group than in
      the conventional group. CONCLUSION: A novel and simple pace-and-ablate technique
      under diaphragmatic electromyography monitoring might be feasible for an
      electrical SVCI.

PMID- 28434452
TI  - The Journal Welcomes Three Associate Editors.

PMID- 28434451
TI  - Editorial overview: Cell architecture: Mechanisms and scales of cellular
      organization and decision making.

PMID- 28434453
TI  - Exploring How to Better Measure and Improve the Quality of Medication
      Reconciliation.

PMID- 28434454
TI  - Measuring to Improve Medication Reconciliation in a Large Subspecialty Outpatient
      Practice.
AB  - BACKGROUND: To assess performance in medication reconciliation (med rec)-the
      process of comparing and reconciling patients' medication lists at clinical
      transition points-and demonstrate improvement in an outpatient setting,
      sustainable and valid measures are needed. METHODS: An interdisciplinary team at
      National Jewish Health (Denver) attempted to improve med rec in an ambulatory
      practice serving patients with respiratory and related diseases. Interventions,
      which were aimed at physicians, nurses (RNs), and medical assistants, involved
      changes in practice and changes in documentation in the electronic health record
      (EHR). New measures designed to assess med rec performance, and to validate the
      measures, were derived from EHR data. RESULTS: Across 18 months, electronic
      attestation that med rec was completed at clinic visits increased from 9.8% to
      91.3% (p <0.0001). Consistent with this improvement, patients with medication
      lists missing dose/frequency for at least one prescription-type medication
      decreased from 18.1% to 15.8% (p <0.0001). Patients with duplicate albuterol
      inhalers on their list decreased from 4.0% to 2.6% (p <0.0001). Percentages of
      patients increased for printing of the medication list at the visit (18.7% to
      94.0%; p <0.0001) and receipt of the printed medication list at the visit (52.3%
      to 67.0%; p = 0.0074). Documentation that patient education handouts were offered
      increased initially then declined to an overall poor performance of 32.4% of
      clinic visits. Investigation of this result revealed poor buy-in and a highly
      redundant process. CONCLUSION: Deriving measures reflecting performance and
      quality of med rec from EHR data is feasible and sustainable over the time
      periods necessary to demonstrate change. Concurrent, complementary measures may
      be used to support the validity of summary measures.

PMID- 28434455
TI  - Creating a Pediatric Joint Council to Promote Patient Safety and Quality,
      Governance, and Accountability Across Johns Hopkins Medicine.
AB  - BACKGROUND: Large multihospital health systems with multiple children's hospitals
      are relatively few in number. With a paucity of national pediatric measures for
      quality and patient safety, there are unique challenges to ensuring consistent
      levels of care across diverse health care delivery settings. At Johns Hopkins
      Medicine, a Pediatric Joint Council was created to help ensure high-quality and
      safe care across a health system encompassing two full-service children's
      hospitals and two community hospitals with significant pediatric volumes across
      two states. APPROACH: Across the health system, a governance, leadership, and
      management structure was developed to coordinate the quality and safety of
      patient care throughout the academic health system. Within the pediatric service
      line, the multidisciplinary Pediatric Joint Council included representation from
      each pediatric entity and was supported by project managers, quality improvement
      (QI) team leaders, QI leads from each entity, infection control, and clinical
      analysts. The Pediatric Joint Council was responsible for setting standards and
      improvement goals, as well as monitoring and improving performance of pediatric
      services across the health system and identifying training gaps and research
      opportunities. CONCLUSION: The Pediatric Joint Council model, as implemented,
      provides a focused structure for coordinated efforts across disparate pediatric
      entities, ensuring horizontal peer learning and entity-specific improvements, as
      well as vertical lines of accountability and central oversight with shared
      governance. This model has served to help identify areas in need of pediatric
      expertise and has facilitated the use of resources from across the entire health
      system focused on improving pediatric care.

PMID- 28434456
TI  - System Changes for Tracking Performance Measures in Tobacco Control: Can Health
      Information Technology Serve as an Accelerant for Moonshot Success in Cancer?

PMID- 28434457
TI  - System Changes to Implement the Joint Commission Tobacco Treatment (TOB)
      Performance Measures for Improving the Treatment of Tobacco Use Among
      Hospitalized Patients.
AB  - BACKGROUND: In 2012 The Joint Commission implemented new Tobacco Treatment (TOB)
      performance measures for hospitals. A study evaluated the impact of a hospital
      based electronic health record (EHR) intervention on adherence to the revised TOB
      measures. METHODS: The study was conducted in two acute care hospitals in New
      York City. Data abstracted from the EHR were analyzed retrospectively from 4,871
      smokers discharged between December 2012 and March 2015 to evaluate the impact of
      two interventions: an order set to prompt clinicians to prescribe pharmacotherapy
      and a nurse-delivered counseling module that automatically populated the nursing
      care plan for all smokers. The study estimated the relative odds of a patient
      being prescribed medication and/or receiving smoking cessation counseling in the
      intervention period compared to the baseline time period. RESULTS: There was a
      modest increase in medication orders (odds ratio [OR], 1.35). In contrast, rates
      of counseling increased 10-fold (OR, 10.54). Patients admitted through surgery
      were less likely to receive both counseling and medication compared with the
      medicine service. CONCLUSION: Hospitalization presents an important opportunity
      to engage smokers in treatment for primary and secondary prevention of tobacco
      related illnesses. EHRs can be leveraged to facilitate integration of TOB measure
      requirements into routine inpatient care; however, the smaller effect on
      prescribing patterns suggests limitations in this approach alone in changing
      clinician behavior to meet this measure. The success of the nurse-focused EHR
      driven intervention suggests an effective tool for integrating the cessation
      counseling component of the new measures and the importance of nursing's role in
      achieving the Joint Commission measure targets.

PMID- 28434458
TI  - Relationship Between State Malpractice Environment and Quality of Health Care in
      the United States.
AB  - BACKGROUND: One major intent of the medical malpractice system in the United
      States is to deter negligent care and to create incentives for delivering high
      quality health care. A study was conducted to assess whether state-level measures
      of malpractice risk were associated with hospital quality and patient safety.
      METHODS: In an observational study of short-term, acute-care general hospitals in
      the United States that publicly reported in the Centers for Medicaid & Medicare
      Services Hospital Compare in 2011, hierarchical regression models were used to
      estimate associations between state-specific malpractice environment measures
      (rates of paid claims, average Medicare Malpractice Geographic Practice Cost
      Index [MGPCI], absence of tort reform laws, and a composite measure) and measures
      of hospital quality (processes of care, imaging utilization, 30-day mortality and
      readmission, Agency for Healthcare Research and Quality Patient Safety
      Indicators, and patient experience from the Hospital Consumer Assessment of
      Healthcare Providers and Systems [HCAHPS]). RESULTS: No consistent association
      between malpractice environment and hospital process-of-care measures was found.
      Hospitals in areas with a higher MGPCI were associated with lower adjusted odds
      of magnetic resonance imaging overutilization for lower back pain but greater
      adjusted odds of overutilization of cardiac stress testing and brain/sinus
      computed tomography (CT) scans. The MGPCI was negatively associated with 30-day
      mortality measures but positively associated with 30-day readmission measures.
      Measures of malpractice risk were also negatively associated with HCAHPS measures
      of patient experience. CONCLUSIONS: Overall, little evidence was found that
      greater malpractice risk improves adherence to recommended clinical standards of
      care, but some evidence was found that malpractice risk may encourage defensive
      medicine.

PMID- 28434459
TI  - Becoming Parent and Nurse: High-Fidelity Simulation in Teaching Ambulatory
      Central Line Infection Prevention to Parents of Children with Cancer.
AB  - BACKGROUND: Ambulatory central-line infections in children with cancer are life
      threatening. Infections are two to three times more frequent in outpatients than
      inpatients, for whom evidence-based bundles have decreased morbidity. Most cancer
      care now takes place at home, where parents perform many of the same tasks as
      nurses. However, parents often feel stressed and unprepared. To address this,
      high-fidelity simulation, which has been effective for teaching novice nurses,
      was evaluated for parent central-line education. METHODS: In a feasibility study
      using a pretest/posttest design, after completion of usual central-line
      education, parents participated in a high-fidelity simulation practice session.
      Parents were assessed in three domains: (1) knowledge of infection prevention;
      (2) psychomotor skill competence; and (3) ability to recognize health care
      provider nonadherence to best practices. Parents also completed a 5-point Likert
      simulation experience survey. RESULTS: A convenience sample of 17 parents
      participated between December 2015 and March 2016. Knowledge median scores
      increased from pre- to posttest from 10 to 15 of 16 points possible (p <= 0.001;
      Wilcoxon signed rank test). Median skills scores increased from pre- to posttest
      from 8 to 12 points of 12 possible (p <= 0.001). Following simulation, median
      recognition scores increased from 3 to 6 with 6 points possible (p <= 0.001). For
      the parent experience survey, 100% of participants strongly agreed or agreed that
      simulation was meaningful for learning central-line care. CONCLUSIONS: As an
      adjunct to usual care central-line education, translation of high-fidelity
      simulation to parent education is a novel approach that shows promise for
      improving central-line care at home in children with cancer.

PMID- 28434460
TI  - Performance Measurement in Rural Communities: The Low-Volume, Large Measurement
      Challenge.

PMID- 28434461
TI  - Effect of black tea consumption on radial blood pulse spectrum and cognitive
      health.
AB  - Black tea consumption has been proven to improve endothelial function and to
      lower the risk of stroke and cognitive impairment. Several effects of black tea
      on cardiovascular system had been surveyed. However, the black tea effect on
      pressure pulse spectrum remains unknown. The study was aimed to investigate the
      influence of black tea on radial blood pressure and Pulse Spectrum. Fourteen
      healthy subjects received water and single doses of black tea (0.05g/Kg) in
      separate weeks. The radial blood pressure and pulse wave were measured and the
      pressure pulses were evaluated using harmonic analysis. This report confirmed
      that black tea consumption (dose=0.05g/Kg) significantly increased third, fifth,
      (P<0.1), sixth, seventh, and eighth harmonics (p<0.05) of radial pressure wave
      comparing to water control. We proposed that black tea may increase cerebral
      blood flow (CBF), which was deduced from the results and from the conclusions of
      previous studies. The results also showed that the harmonic components of
      pressure pulse could be the vascular kinetic index that assessed the hemodynamic
      status in each time frame before and after consumption of black tea.

PMID- 28434462
TI  - The effects of Tai Chi on physical and psychosocial function among persons with
      multiple sclerosis: A systematic review.
AB  - OBJECTIVES: Conduct a systematic review to evaluate the effects of Tai Chi on
      physical and psychosocial function among individuals with Multiple Sclerosis.
      METHODS: An electronic literature search of 12 databases using controlled
      vocabulary function and keywords from inception through August 2016. All Tai Chi
      intervention studies assessing physical and psychosocial function among persons
      with Multiple Sclerosis were included. Study quality was scored using an
      established tool examining 16 study elements (range=0-32). RESULTS: A total of 91
      articles were retrieved, with 3 additional articles identified through reviewing
      bibliographies of relevant articles. A total of 8 studies (randomized controlled
      trials, n=3; quasi-experimental, n=5) enrolled 193 participants with Multiple
      Sclerosis. Studies were conducted in the USA (n=3), Europe (n=3), Iran, (n=1),
      and India (n=1). A total of 3 studies reported using the Yang style of Tai Chi
      (not specified, n=5 studies). The Tai Chi intervention averaged 27 sessions over
      11 weeks. Study quality scores for the randomized controlled trials had a mean
      score of 23 (range 19-26), while quality scores for quasi-experimental studies
      had a mean score of 20 (range 13-26). Overall, participants enrolled in Tai Chi
      had better balance, gait and flexibility, less fatigue and depression, and better
      quality of life after the intervention; though mixed results were reported.
      CONCLUSION: The results indicate that Tai Chi is likely safe and may provide
      physical and psychosocial benefits in individuals with Multiple Sclerosis.
      Further research is needed using more rigorous study designs to assess the
      benefits of Tai Chi for individuals with Multiple Sclerosis.

PMID- 28434463
TI  - Effects of prenatal yoga on women's stress and immune function across pregnancy:
      A randomized controlled trial.
AB  - OBJECTIVE: The effects of prenatal yoga on biological indicators have not been
      widely studied. Thus, we compared changes in stress and immunity salivary
      biomarkers from 16 to 36 weeks' gestation between women receiving prenatal yoga
      and those receiving routine prenatal care. DESIGN: For this longitudinal,
      prospective, randomized controlled trial, we recruited 94 healthy pregnant women
      at 16 weeks' gestation through convenience sampling from a prenatal clinic in
      Taipei. Participants were randomly assigned to intervention (n=48) or control
      (n=46) groups using Clinstat block randomization. INTERVENTION: The 20-week
      intervention comprised two weekly 70-min yoga sessions led by a midwife certified
      as a yoga instructor; the control group received only routine prenatal care. MAIN
      OUTCOME MEASURES: In both groups, participants' salivary cortisol and
      immunoglobulin A levels were collected before and after yoga every 4 weeks from
      16 to 36 weeks' gestation. RESULTS: The intervention group had lower salivary
      cortisol (p<0.001) and higher immunoglobulin A (p<0.001) levels immediately after
      yoga than the control group. Specifically, the intervention group had
      significantly higher long-term salivary immunoglobulin A levels than the control
      group (p=0.018), and infants born to women in the intervention group weighed more
      than those born to the control group (p<0.001). CONCLUSION: Prenatal yoga
      significantly reduced pregnant women's stress and enhanced their immune function.
      Clinicians should learn the mechanisms of yoga and its effects on pregnant women.
      Our findings can guide clinicians to help pregnant women alleviate their stress
      and enhance their immune function.

PMID- 28434464
TI  - Development of a falls reduction yoga program for older adults-A pilot study.
AB  - OBJECTIVES: Work with local rural organizations to develop an evidence-based
      hatha yoga program intended to improve core strength and balance to reduce falls
      risk. Feasibility determined by successful recruiting, intervention and
      evaluation of participants and acceptable frequency of adverse events. DESIGN:
      Single-arm pilot study. SETTING: Rural Wisconsin town of 4200 people.
      INTERVENTION: Eight week yoga program with weekly group classes and home yoga
      practice three times per week. MAIN OUTCOME MEASURES: The primary outcomes were
      (1) ability to enroll at least 20 participants, (2) participant completion of
      intervention and post-intervention evaluation, and (3) adverse event description
      and frequency. RESULTS: A convenience sample of 20 adults over age 59 was
      enrolled and started the program with one drop out. Participants attended a mean
      of 7.1 (SD 1.47) of the 8 classes and a total of 141 out of 160 (88.1%) classes.
      Nineteen (95%) completed follow up evaluation. Participants reported 4 falls in
      the month before the intervention and 1 fall the month before the post
      intervention evaluation (p=0.34). No other serious adverse events occurred.
      CONCLUSIONS: This project suggests an evidence-based yoga program designed to
      improve core strength and balance is feasible and acceptable to participants.
      Future research will include a randomized trial to assess impact on falls risk.

PMID- 28434465
TI  - Therapeutic singing as an early intervention for swallowing in persons with
      Parkinson's disease.
AB  - OBJECTIVE: For persons with Parkinson's disease (PD), secondary motor symptoms
      such as swallow impairment impact the quality of life and are major contributors
      to mortality. There is a present need for therapeutic interventions aimed at
      improving swallow function during the early stages of PD. The purpose of this
      pilot study was to examine the effects of a group therapeutic singing
      intervention on swallowing in persons with PD with no significant dysphagia
      symptoms. DESIGN: Cohort study. SETTING: University in the United States.
      PARTICIPANTS: Twenty-four participants with PD. INTERVENTION: Eight weeks of
      group therapeutic singing. MAIN OUTCOME MEASURES: Electromyography (EMG) was used
      to assess muscle activity associated with swallow pre and post the group singing
      intervention. Swallow quality of life (SWAL-QOL) and the Unified Parkinson's
      Disease Rating Scale (UPDRS) were also obtained pre- and post-intervention.
      RESULTS: Participants reported minimal difficulty with swallowing, yet results
      revealed a significant increase in EMG outcome measures, as well as significant
      improvement in UPDRS total and UPDRS motor scores. No significant differences
      were revealed for SWAL-QOL. CONCLUSION: Increases in EMG timing measures may
      suggest that group singing results in the prolongation of laryngeal elevation,
      protecting the airway from foreign material for longer periods of time during
      swallow. Combined with the improvement in UPDRS clinical measures, therapeutic
      singing may be an engaging early intervention strategy to address oropharyngeal
      dysphagia while also benefiting additional clinical symptoms of PD.

PMID- 28434466
TI  - Cost-effectiveness of acupuncture in an employee population: A retrospective
      analysis.
AB  - OBJECTIVES: To determine whether acupuncture is a cost-effective adjunct to usual
      care for Mayo Clinic employees and their dependents experiencing pain symptoms.
      DESIGN: Retrospective review of the medical and billing records of 466 employee
      patients and their dependents who had received acupuncture as part of their care
      and 466 propensity score-matched control patients. INTERVENTIONS: Usual care in
      combination with acupuncture compared with usual care alone. MAIN OUTCOME
      MEASURES: The primary outcome measure was the total costs of care for all medical
      care and pharmacy services incurred from 1year before the index visit to 14
      months after the index date. Secondary outcomes included the number of hospital
      visits, total inpatient days, emergency department visits, primary care or
      general medicine office visits, specialty office visits, and physical therapy
      services. Pain scores (patient-rated scores from 0 to 10) were extracted from the
      medical record, if available. RESULTS: Costs of care were similar between the 2
      groups. No cost savings were noted for the acupuncture group. CONCLUSIONS:
      Several limitations to the study may have precluded a finding of cost
      effectiveness. Future studies should include prospective evaluation of costs and
      other outcomes in a comparison between acupuncture and usual care in a randomized
      control trial.

PMID- 28434467
TI  - Abdominal and auricular acupuncture reduces blood pressure in hypertensive
      patients.
AB  - INTRODUCTION: Hypertension is an important risk factor of cardiovascular disease
      (CVD), which is associated with premature death, myocardial infarction, stroke,
      peripheral vascular disease, and renal disease. The goal of the present study was
      to use a randomized controlled clinical trial to explore and compare the
      effectiveness of abdominal and auricular acupuncture on blood pressure in 440
      subjects with and without obesity. METHODS: Four hundred participants were
      recruited and randomized to one of four groups: cases and controls receiving
      auricular acupuncture (204 subjects) and cases and controls receiving abdominal
      electroacupuncture (196 subjects). Blood pressure and anthropometric parameters
      were measured before and after the intervention period. In order to match the
      initial diet of the groups, participants were required to follow an isocaloric
      diet for two weeks before the trial, and a low-calorie diet for 6 weeks during
      the intervention period. RESULTS: We observed a significant time dependent
      improvement in the systolic blood pressure measurements in the abdominal
      intervention group, although this improvement was more pronounce in the first
      period of study. Of note, in the auricular intervention group, a significant
      increasing in the level of SBP was detected. Importantly no statistically
      significant changes were found in the corresponding sham groups. CONCLUSIONS: Our
      findings demonstrated that abdominal electro-acupuncture for 6 weeks reduced both
      systolic and diastolic blood pressure and auricular acupuncture had a short-term
      adverse effect on both SBP and DBP.

PMID- 28434468
TI  - The effect of chinese herbal medicine Banxia Baizhu Tianma Decoction for the
      treatment of vertebrobasilar insufficiency vertigo: A systematic review and meta
      analysis of randomized controlled trials.
AB  - OBJECTIVES: Banxia Baizhu Tianma Decoction (BBTD) is widely used to treat
      vertebrobasilar insufficiency vertigo (VBIV) in China, but its efficacy remains
      largely unexplored. We systemically summarized relevant evidence from randomized
      controlled trials (RCTs) to assess the therapeutic effect of BBTD. METHODS: Seven
      electronic databases were searched for relevant electronic studies published
      before July 2016. We evaluated RCTs that compared BBTD, anti-vertigo drugs and a
      combination of BBTD and anti-vertigo drugs. We performed a meta-analysis in
      accordance with the Cochrane Collaboration criteria. The outcomes were clinical
      efficacy (CE), blood flow velocity of the vertebrobasilar artery by transcranial
      Doppler (TCD), and adverse effects. RESULTS: Twenty-seven studies with a total of
      2796 patients were identified. Compared with anti-vertigo drugs, BBTD showed
      slight effects on CE (n=350; RR, 1.09; 95% CI, 1.01-1.18; p=0.03; I2=0%);
      however, BBTD plus anti-vertigo drugs (BPAD) significantly improved the clinical
      efficacy (n=2446; RR, 1.20; 95% CI, 1.16-1.24; p<0.00001; I2=0%) and accelerated
      the blood flow velocity of the left vertebral artery (LVA) (n=1444; WMD,
      5.21cm/s; 95% CI, 3.72-6.70cm/s; p<0.00001; I2=91%), the blood flow velocity of
      the right vertebral artery (RVA) (n=1444; WMD, 5.45cm/s; 95% CI, 4.02-6.88cm/s;
      p<0.00001; I2=89%), and the blood flow velocity of the basilar artery (BA)
      (n=1872; WMD, 5.20cm/s; 95% CI, 3.86-6.54cm/s; p<0.00001; I2=90%). Adverse
      effects were mentioned in six studies. CONCLUSIONS: The current evidence
      indicates that BPAD is effective for the treatment of VBIV, but the efficacy and
      safety of BBTD is uncertain because of the limited number of trials and low
      methodological quality. Hence, high-quality and adequately powered RCTs are
      warranted.

PMID- 28434469
TI  - The North American yoga therapy workforce survey.
AB  - OBJECTIVE: To describe the personal, professional, practice, service and consumer
      characteristics of the North American yoga therapy workforce. DESIGN: Cross
      sectional, descriptive survey developed and informed by the contemporary
      workforce literature. A link to the e-survey was distributed to members of the
      International Association of Yoga Therapists. RESULTS: 367 members responded
      (~20% of eligible participants). Most were aged 40-69 years (88%) and female
      (91%). Almost half (42%) identified as a "seasoned yoga therapist" and few (9%)
      graduated from an accredited 800-h yoga therapy program. An average of 8h/week
      was spent in clinical practice with many (41%) earning an annual income of
      <US$10,000 from yoga therapy. Practice was informed by twenty different styles of
      yoga. Urban (39%) and suburban (38.1%) regions were the most common locations of
      practice. Most therapists conducted therapeutic yoga classes (91%) and 1:1
      sessions (94%), with more than half delivering 1-10 therapeutic classes/month
      (53%) and 1-10 1:1 sessions/month (52%). Conditions seen most frequently were
      anxiety (77%), back/neck pain (77%) and joint pain/stiffness (67%). CONCLUSION:
      While yoga therapists shared demographic characteristics with other complementary
      and integrative health (CIH) providers, they tended to work less and earn less
      than their CIH counterparts. Yoga therapists were less likely to work in rural
      settings, possibly contributing to the underutilization of yoga in underserved
      populations. Improving access to yoga therapy services, identifying common core
      components across the various styles of yoga, and building a stronger evidence
      base for key health indications may increase acceptance of, and demand for, yoga
      therapy.

PMID- 28434470
TI  - Complementary and alternative medicine among hospitalized pediatric patients.
AB  - OBJECTIVES: To estimate the prevalence and describe the characteristics of
      complementary and alternative medicine (CAM) use among hospitalized children, and
      to discover the awareness of medical staff regarding CAM use. DESIGN/SETTING:
      Parents of children aged 0-18 years admitted to the Pediatric Division at Assaf
      Harofeh Medical Center in Israel between January and July of 2015 (n=146) were
      provided a questionnaire regarding socio-economic status and evaluating the CAM
      use. The medical charts of the participants were reviewed in order to establish
      whether or not CAM use was documented. RESULTS: Of those who completed the
      questionnaire, 78 (54.3%) were using CAM. The major indications for CAM use were
      colic and teething. CAM use was advised by the family in 44.9%, physician 34.6%,
      pharmacist 34.6%, friends 30.8%, previous experience 23.1, advertisements 18%,
      nurses 6.4%, and homeopaths 2.6%. The family physician was aware of CAM use was
      in 42%. During the admission, only 5 patients were asked about CAM use (3.4%) by
      the medical staff. Reviewing the medical charts revealed there was no
      documentation of CAM use in any of the participants. Socio-demographic analysis
      of our population revealed no differences between users and non users of CAM, but
      significant differences in belief in CAM (p=0.018) were found. CAM use was age
      related; the older the child the less the use (p=0.010). CONCLUSION: CAM use is
      common among hospitalized pediatric patients and is often overlooked by the
      medical staff. CAM use should be included in the medical history.

PMID- 28434471
TI  - Factors associated with complementary medicine use in pediatric musculoskeletal
      conditions: Results from a national survey.
AB  - OBJECTIVES: Complementary and alternative medicine (CAM) use is common in
      children, but its use has only been investigated in children with musculoskeletal
      conditions (MSK) to a limited extent. We aimed to characterize factors associated
      with CAM use in children with MSK conditions. METHODS: Within the 2012 National
      Health Interview Survey dataset (including its child CAM supplement), we examined
      factors associated with CAM use in children with MSK conditions and performed an
      analysis examining the perceived usefulness of CAM therapies for MSK conditions.
      RESULTS: Overall, there were 10,218 children in the dataset. 28.0% of children
      with MSK conditions used CAM, compared to 8.8% of children without MSK
      conditions. Gender (p=0.003), region (p=0.001), race (p=0.001), parental CAM use
      (p<0.001), education (<0.001), and having anxiety, stress or depression (p=0.030)
      were correlated with CAM use. Among 90 children who reported on CAM use, 89.7%
      said that CAM helped some or a great deal for their MSK condition. CONCLUSIONS:
      Several factors, particularly parental education and parental CAM use, were
      associated with CAM use, and self-reported improvement rates were high.
      Interventional trials are needed to determine the efficacy of specific CAM
      therapies for treating different MSK conditions in children.

PMID- 28434472
TI  - Tai Chi with mental imagery theory improves soleus H-reflex and nerve conduction
      velocity in patients with type 2 diabetes.
AB  - OBJECTIVES: Diabetes is a disease that leads to damage to the peripheral nerves
      which may eventually cause balance instability. The purpose of this study was to
      determine the effect of 8 weeks of Tai Chi (TC) training combined with mental
      imagery (MI) on soleus H-reflex and nerve conduction velocity (NCV) of the sural
      and superficial peroneal nerves in people with diabetes. DESIGNS: Quasi
      experimental, one group pretest-posttest design. SETTING: Human Research
      Laboratory. INTERVENTIONS: A series of Yang style of Tai Chi classes with mental
      imagery, one hour, two sessions per week for 8 weeks was done. MAIN OUTCOME
      MEASURES: The Activities-specific Balance Confidence (ABC) Scale, Functional
      Reach Test (FRT), and One Leg Standing Test (OLS) were measured as functional
      data. Hoffman reflex (H-reflex), and sural and superficial peroneal NCV were
      measured as main outcomes. RESULTS: All functional outcomes measures were
      significantly improved after the intervention (p<0.01). In the H-reflex, there
      was a significant increase in amplitude (MUV) after completing 8 weeks of TC
      exercise (p=0.02). In the sural nerve, the velocity (p=0.01), amplitude (p=0.01),
      and latency (p=0.01) were significantly improved between pre and post-test. In
      the superficial peroneal nerve, significant improvements were observed in
      (p=0.02) and latency (p=0.01), but not in amplitude (MUV) (p>0.05). CONCLUSIONS:
      Combining TC intervention with MI theory showed an improvement in the H-reflex
      and NCV tests, which suggests improved balance and walking stability.

PMID- 28434473
TI  - The effect of applying pressure to the LIV3 and LI4 on the symptoms of
      premenstrual syndrome: A randomized clinical trial.
AB  - OBJECTIVE: To evaluate the effect of simple acupressure protocol in LIV3, LI4 and
      placebo points on the quality of life (QOL) in women with premenstrual syndrome
      (PMS). METHOD: This paper reports a randomized, single blinded clinical trial. 97
      participants (students in of Hormozgan University of Medical Sciences, Iran) with
      PMS were allocated to three groups to receive 20min acupressure on different
      acupoints for 14days before menstruation for three consecutive menstrual cycles
      (training and then two cycles self applied acupressure). The acupoints were LIV3
      and LI4; one group received acupressure at a placebo point. Each participant
      completed the PSST scale (to determine PMS severity), HADS scale (for depression
      and anxiety), and quality of life SF12. RESULTS: The number of people with
      moderate/severe PMS decreased in LIV3 and LI4 acupressure groups by the second
      and third cycles compared with the placebo group (p<0.04). Moreover, depression
      and anxiety scores significantly decreased in the LIV3 and LI4 groups by the
      second and third cycles compared with the placebo group (p<0.05).Analyzing the
      score of SF12 fields in the second and third cycles showed a significant
      difference in all dimensions between the intervention and placebo groups. There
      was no significant difference between LIV3 and LI4 acupressure groups in decrease
      of PMS symptoms, anxiety and depression and improving SF12scores (p<0.05).
      CONCLUSION: Performing the simple acupressure protocol at LIV3 and LI4 is an
      effective method to decrease the severity of PMS symptoms, anxiety and
      depression, and to improve the QOL. Pressure at LIV3 and LI4 appears to be
      equally effective.

PMID- 28434474
TI  - Chinese herbal medicine adjunct therapy in patients with acute relapse of
      multiple sclerosis: A systematic review and meta-analysis.
AB  - BACKGROUND: Many patients with multiple sclerosis (MS) resort to complementary
      and alternative medicine, which is used in 33%-80% of MS patients in the
      developed country. The purpose of this study is to assess the efficacy and safety
      of Chinese herbal medicine (CHM) as an adjunct therapy of patients with acute
      relapse of MS. METHODS: Six databases were searched for randomized-controlled
      trial of CHM for acute relapse of MS. The risk of bias was assessed by using the
      twelve criteria recommended by the Cochrane Back Review Group. The primary
      outcome measures of interest are the Expanded Disability Status Score, annual
      relapse frequency, annual relapse rate, and annual relapse interval. The
      secondary outcome measures are the clinical efficacy rate and adverse events. The
      selection criteria of high-frequency herbs for MS are those with cumulative
      frequency over 50%. We analyzed the data using Review Manager (version 5.3).
      RESULTS: A total of 1100 participants were included in the 20 studies from 2004
      to 2015. The number of risk of bias which met the criteria varied from 5/12 to
      7/12. The top 5 most frequently used herbs are ordinally Radix Angelicae
      Sinensis, Radix Glycyrrhizae, Radix Paeoniae Rubra, Radix Rehmanniae Preparata,
      and Bombyx Batryticatus. The meta-analysis showed a significant effect of CHM for
      improving Expanded Disability Status Score (P<0.01), annual relapse frequency
      (P<0.01) and the total clinical efficacy rate (P<0.01) compared with western
      conventional treatment. In analysis of annual relapse rate and annual relapse
      interval, there was a significant difference between CHMs and western
      conventional treatment (P<0.01). Adverse effects were monitored in 6 studies, and
      were well tolerated in all MS patients. CONCLUSIONS: The available evidence from
      present study supported but limited to recommend the routine use of CHM adjuvant
      therapy for MS because of the poor methodological quality and clinical
      heterogeneity. However, we identified an area that is worthy of further study.
      Furthermore, we selected high frequent use of CHMs as a promising candidate for
      further clinical application and MS trials. Further rigorous randomized
      controlled trials are needed.

PMID- 28434475
TI  - Music listening alleviates anxiety and physiological responses in patients
      receiving spinal anesthesia.
AB  - OBJECTIVE: The aim of this study was to explore the effects of listening to music
      on the anxiety levels and physiological responses of surgical patients receiving
      spinal anesthesia. METHODS: An experimental design was used in the study with an
      experimental group (n=50) and a control group (n=50). The experimental group
      received 30min of musical intervention and routine nursing care in the Post
      Anesthesia Care Unit (PACU) while the control group received only routine nursing
      care. RESULTS: The study found significant differences in both anxiety and
      physiological indices between the two groups. The mean score of the State-Trait
      Anxiety Inventory (STAI) in the study group decreased from a pre-test score of
      59.0 to a post-test score of 31.20 (t=28.63, p<0.001). Physiological indices such
      as heart rate (t=2.61, p=0.012), respiration rate (t=2.29, p=0.026), systolic
      blood pressure (t=2.30, p=0.026), and diastolic blood pressure (t=3.02, p=0.004)
      decreased significantly as well. Control group was not seeing significant changes
      from pre-op values. CONCLUSION: Listening to music while in the recovery room may
      decrease the level of anxiety in surgical patients receiving spinal anesthesia.
      The results of this study can serve as a reference for PACU nurses in utilizing
      music listening programs to achieve the goal of holistic care.

PMID- 28434476
TI  - A qualitative approach exploring the acceptability of yoga for minorities living
      with arthritis: 'Where are the people who look like me?'
AB  - OBJECTIVES: To examine the acceptability of yoga research tailored to recruit and
      retain a minority population (both English and Spanish speaking) with arthritis.
      Yoga research for arthritis often underrepresents minorities and acceptability
      for this population has not previously been investigated. DESIGN: Acceptability
      was evaluated using retention, adherence, journals, and semi-structured exit
      interviews from twelve participants with osteoarthritis or rheumatoid arthritis
      undergoing an 8-week yoga intervention. Journal quotes were analyzed using
      content analysis techniques. NVivo software was used to organize transcripts and
      assemble themes. Two methods of triangulation (data and investigator) were used
      to overcome potential bias from a single-perspective interpretation. Exit
      interview comments were content analyzed using a card sort method. The study was
      designed with a cultural infrastructure including a multicultural research team,
      translators, and bilingual materials and classes, to facilitate trust and
      acceptability for primarily Hispanic and Black/African-American adults. SETTING:
      Washington, D.C. metropolitan area, USA. RESULTS: On average participants
      attended 10 of 16 classes, with home practice 2-3days a week. All who completed
      were still practicing yoga three-months later. Qualitative narrative analysis
      identified major themes related to facilitating factors and barriers for yoga
      practice, self-efficacy, and support. Participant comments indicated that
      offering an arthritis-based yoga intervention and using a culturally congruent
      research design was found to be acceptable. CONCLUSIONS: As yoga research grows,
      there is a need to understand and promote acceptability for typically under
      represented populations. This study attempts to inform the expansion of
      multicultural research designed to recruit and retain those from diverse
      backgrounds.

PMID- 28434477
TI  - Niuhuang Jiangya Preparation (a traditional Chinese patent medicine) for
      essential hypertension: A systematic review.
AB  - OBJECTIVES: Niuhuang Jiangya Preparation (NHJYP) is one of the most commonly used
      traditional Chinese patent medicines for essential hypertension (EH) in China.
      Our meta-analysis performed a systematic evaluation on the therapeutic efficacy
      and safety of NHJYP for EH. DESIGN: Systematic review and meta-analysis. METHODS:
      PubMed, Embase, the Cochrane library, CNKI,VIP, Sinomed, and Wanfang Database
      were searched up to June 2015. Randomized controlled trials (RCTs) comparing
      NHJYP or combined with western antihypertensive drugs (WAD) versus WAD were
      included. Quality of each trial was assessed according to the Cochrane Reviewers'
      Handbook 5. 1.0. Statistical software (RevMan 5.3) was used for data analysis.
      The primary outcome was categorical or continuous blood pressure, and the
      secondary outcome was Traditional Chinese Medicine (TCM) syndrome. RESULTS: 12
      RCTs including 1651 cases were identified. The methodological quality of trials
      was low. Meta-analysis showed that, firstly, NHJYP used alone compared with WAD
      had no significant effect on BP reduction; however, subgroup analysis was used
      based on whether apply TCM diagnostic criteria in recruitment. It was suggested
      that, for population that applied TCM diagnostic criteria, RR=1.35,95% CI:1.17
      1.56,P<0.0001; for population that didn't apply TCM diagnostic criteria,
      RR=0.96,95% CI:0.70-1.33,P=0.81.Reduction in systolic blood pressure (SBP) levels
      showed similar results. But there was no significant difference in improving
      diastolic blood pressure (DBP). Secondly, we found that NHJYP plus WAD probably
      lower BP (RR=1.13,95% CI:1.03-1.24,P=0.01)and improve TCM symptoms than WAD only.
      And subgroup analysis suggested significant BP reduction effect for population
      that applied TCM diagnostic. No serious adverse events were reported.
      CONCLUSIONS: Our review indicated that NHJYP has some beneficial effects in EH
      patients with liver-yang hyperactivity and abundant phlegm-heat syndrome.
      However, the evidence is not reliable enough. To produce definite evidence, more
      rigorously designed trials are needed.

PMID- 28434480
TI  - How to assess and manage cardiovascular risk associated with lipid alterations
      beyond LDL.
AB  - BACKGROUND AND AIMS: The maintenance of clinically recommended levels of low
      density lipoprotein cholesterol (LDL-C) through a statin therapy is a gold
      standard in the management of patients with dyslipidaemia and cardiovascular
      disease (CVD). However, even when LDL-C levels are at or below clinically
      recommended target levels, residual cardiovascular (CV) risk still remains.
      Therefore, assessing lipoproteins beyond LDL-C in managing CV risk is imperative.
      METHODS: A working group of clinical experts have assessed the role of
      lipoproteins other than LDL-C in identifying the CV risk in patients with
      dyslipidaemia and CVD and in the management of atherogenic dyslipidaemia
      associated with a number of other diseases. The recommendations, in line with the
      European guidelines, are presented. RESULTS: A thorough evaluation of clinical
      data by the expert working group resulted in recommendations to consider non-high
      density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), remnant
      cholesterol and lipoprotein(a) (Lp[a]) as biomarkers of residual CV risk in
      patients with CVD. Elevated Lp(a) levels were also suggested to be a causal
      factor. The experts highlighted the significance of non-HDL-C and triglycerides
      (TG) in atherogenic dyslipidaemia associated with type 2 diabetes, metabolic
      syndrome, chronic kidney disease (CKD) and familial combined hyperlipidaemia
      (FCH). The working group recommended combinatorial therapeutic approaches in high
      risk patients, including agents impacting on TG and HDL-C levels. CONCLUSIONS:
      Evaluation of a lipoprotein landscape when LDL-C levels remain low strongly
      supports the role of non-HDL-C, Lp(a) and TGs in identifying patients with
      increased residual risk of CV and in selecting their treatment strategy.

PMID- 28434481
TI  - Is there a role for lifestyle changes in cardiovascular prevention? What, when
      and how?
AB  - BACKGROUND AND AIMS: Lifestyle has been found to play an important role in the
      prevention of cardiovascular disease (CVD). There is evidence to suggest that if
      lifestyle factors are modified successfully, the relative risk of CVD can be
      reduced. Risk factors for CVD such as high blood pressure, diabetes mellitus and
      dyslipidaemias can be modified by lifestyle changes. The main aim of this article
      is to provide best practice approaches and support for healthcare professionals
      on the role of lifestyle changes in the prevention of CVD. METHODS: A working
      group of experts discussed existing guidelines, clinical practice and evidence,
      and provided their recommendations on ten topics concerning the role of lifestyle
      in CVD prevention. These topics covered important lifestyle factors as well as
      tools/approaches to assess or encourage lifestyle changes. RESULTS: The group of
      clinical experts collaborated to provide their opinion on the following topics:
      one diet versus customised diets; the role of alcohol consumption in a healthy
      diet; a diet based on nutrient composition or on whole foods; a Mediterranean
      versus low-fat diet; the role of dietary supplements; physical activity; smoking
      cessation; the role of a nutritionist/dietitian in a CVD risk multidisciplinary
      team; tools to be implemented to assess diet, physical activity and smoking
      status; and the most effective approaches to encourage lifestyle changes.
      CONCLUSIONS: The expert working group agreed that lifestyle changes were
      important in preventing CVD and provided recommendations which complemented
      current guidance and increased clarity on several topics.

PMID- 28434482
TI  - How to implement clinical guidelines to optimise familial hypercholesterolaemia
      diagnosis and treatment.
AB  - BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is a genetic disorder
      associated with significantly elevated plasma low-density lipoprotein cholesterol
      (LDL-C) and premature coronary heart disease (CHD). Optimal management of FH
      relies on early identification and treatment with statins alone or in combination
      with other lipid-lowering therapies. A lack of awareness of FH and its
      manifestations among primary care physicians and specialists has led to many
      individuals being misdiagnosed in the early stages of the disease, further
      increasing the risk of CHD and requiring much more intensive lipid-lowering
      strategies. Therefore, implementing clinical guidelines to optimise the diagnosis
      and treatment of FH is essential. METHODS: A working group of clinical experts
      managing FH patients in their daily practice collaborated in order to provide
      healthcare professionals with a practical evidence-based guide to streamline
      early diagnosis and treatment of FH. RESULTS: Following thorough evaluation of
      available data and clinical guidelines, the expert working group provided
      recommendations on how to detect patients with a suspicion of FH; criteria for
      clinical and genetic diagnoses of FH; how to assess atherosclerosis in primary
      care and identify patients at the highest risk; follow-up approaches for
      patients' families; the most optimal treatment combinations; and when to start
      lipid-lowering therapy in children with FH. CONCLUSIONS: The expert working group
      placed great importance on an individualised approach in the management of FH and
      highlighted the unmet need for both improved education and communication with the
      laboratory for physicians when LDL-C levels are significantly elevated. Screening
      high-risk individuals, or cascade screening, is the most cost-effective way of
      identifying FH cases and initiating adequate statin therapy alone or in
      combination with other lipid-lowering therapies. In the case of severe FH, where
      plasma LDL-C levels remain high following maximum-tolerated statin and ezetimibe
      treatment, PCSK9 inhibitors should be considered.

PMID- 28434483
TI  - What imaging techniques should be used in primary versus secondary prevention for
      further risk stratification?
AB  - BACKGROUND AND AIMS: An accurate assessment of the cardiovascular (CV) risk of an
      individual is key for guiding the appropriate treatment strategy for
      cardiovascular disease (CVD). Although conventional risk factors for CVD are well
      established, there can be substantial variation in the extent of atherosclerosis
      between patients. The use of a variety of imaging modalities can be beneficial in
      the primary prevention stage and in the classification of an individual's CV
      risk. Therefore, appropriate implementation of these imaging techniques for risk
      assessment purposes, in line with clinical guidelines, can influence the outcomes
      of CVD prevention. METHODS: The expert working group collaborated to review
      current invasive and non-invasive imaging techniques available to healthcare
      practitioners and how they can be used in the measurement of preclinical vascular
      damage and CV risk assessment. RESULTS: After evaluation of the current guideline
      recommendations and clinical data available, the expert working group
      collaborated to produce recommendations regarding the use of imaging in the risk
      stratification in primary prevention, CV risk in peri-acute coronary syndrome and
      CV risk assessment in secondary prevention. CONCLUSIONS: Overall, a variety of
      both invasive and non-invasive imaging modalities were highlighted by the expert
      working group as having the potential to assist in the risk assessments of
      patients at risk of CVD. These imaging techniques can be utilised in both primary
      and secondary prevention strategies and have the potential to be important risk
      modifiers, improving the outcome of CV risk assessment.

PMID- 28434484
TI  - Practical aspects in the management of statin-associated muscle symptoms (SAMS).
AB  - BACKGROUND AND AIMS: Statin-associated muscle symptoms (SAMS) frequently cause
      statin non-adherence, switching and discontinuation, contributing to adverse
      cardiovascular (CV) outcomes. Therefore, the management of SAMS is key in the
      effective treatment of patients with cardiovascular disease (CVD), through
      achievement of maximum-tolerated statin dosing and other practical aspects. The
      aim of this article is to provide practical, focused advice for healthcare
      professionals on the management of patients with SAMS. METHODS: An expert working
      group combined current evidence, published guidelines and experiences surrounding
      a number of topics concerning SAMS to provide recommendations on how to best
      assess and manage this condition and reach the highest tolerated dose of statin
      for each individual patient. RESULTS: The group collaborated to provide guidance
      on definitions in the SAMS field, psychological issues, re-challenging and
      switching treatments, as well as interpretation of current guidelines and optimal
      treatment of SAMS in different patient populations. An algorithm was developed to
      guide the management of patients with SAMS. In addition, the expert working group
      considered some of the more complex scenarios in a series of frequently asked
      questions and suggested answers. CONCLUSIONS: The expert working group gave
      recommendations for healthcare professionals on the management of SAMS but
      highlighted the importance of tailoring the treatment approach to each individual
      patient. Evidence supporting the role of nutraceuticals and complementary
      therapies, such as vitamin D, was lacking, however the majority of the group
      favoured combination therapy with ezetimibe and the addition of PCSK9 inhibitors
      in high-risk patients.

PMID- 28434485
TI  - Insulin affordability.

PMID- 28434486
TI  - Bariatric surgery in adolescents.

PMID- 28434487
TI  - Bariatric surgery in adolescents - Author's reply.

PMID- 28434488
TI  - Analysis of the MAVIDOS trial - Author's reply.

PMID- 28434489
TI  - Analysis of the MAVIDOS trial.

PMID- 28434490
TI  - Semaglutide, lipid-lowering drugs, and NAFLD.

PMID- 28434491
TI  - Semaglutide, lipid-lowering drugs, and NAFLD - Author's reply.

PMID- 28434492
TI  - Correction to Lancet Diabetes Endocrinol 2017: 5: 125-33.

PMID- 28434493
TI  - Correction to Lancet Diabetes Endocrinol 2017; 5: 240-41.

PMID- 28434494
TI  - Correction to Lancet Diabetes Endocrinol 2017: 5: 174-83.

PMID- 28434495
TI  - Dysfunction of the Cerebral Glucose Transporter SLC45A1 in Individuals with
      Intellectual Disability and Epilepsy.
AB  - Glucose transport across the blood brain barrier and into neural cells is
      critical for normal cerebral physiologic function. Dysfunction of the cerebral
      glucose transporter GLUT1 (encoded by SLC2A1) is known to result in epilepsy,
      intellectual disability (ID), and movement disorder. Using whole-exome
      sequencing, we identified rare homozygous missense variants (c.526C>T
      [p.Arg176Trp] and c.629C>T [p.Ala210Val]) in SLC45A1, encoding another cerebral
      glucose transporter, in two consanguineous multiplex families with moderate to
      severe ID, epilepsy, and variable neuropsychiatric features. The variants
      segregate with the phenotype in these families, affect well-conserved amino
      acids, and are predicted to be damaging by in silico programs. Intracellular
      glucose transport activity of the p.Arg176Trp and p.Ala210Val SLC45A1 variants,
      measured in transfected COS-7 cells, was approximately 50% (p = 0.013) and 33% (p
      = 0.008) lower, respectively, than that of intact SLC45A1. These results indicate
      that residues at positions 176 and 210 are critical for the glucose transport
      activity of SLC45A1. All together, our data strongly suggest that recessive
      mutations in SLC45A1 cause ID and epilepsy. SLC45A1 thus represents the second
      cerebral glucose transporter, in addition to GLUT1, to be involved in
      neurodevelopmental disability. Identification of additional individuals with
      mutations in SLC45A1 will allow better definition of the associated phenotypic
      spectrum and the exploration of potential targeted treatment options.

PMID- 28434497
TI  - Letter From the Editor: Surviving Three Lifetimes of Infectious Diseases.

PMID- 28434496
TI  - A Pink Tumor: Angiolymphoid Hyperplasia With Eosinophilia.

PMID- 28434498
TI  - Imaging of Head and Neck Infections: Diagnostic Considerations, Potential Mimics,
      and Clinical Management.

PMID- 28434499
TI  - Imaging of Spine Infection.

PMID- 28434500
TI  - Infections of the Brain and Meninges.

PMID- 28434501
TI  - Pneumonia.

PMID- 28434502
TI  - Current Updates on Pediatric Pulmonary Infections.

PMID- 28434503
TI  - Cardiac Infections.

PMID- 28434504
TI  - Imaging of Osteomyelitis of the Extremities.

PMID- 28434505
TI  - Imaging of Musculoskeletal Soft Tissue Infection.

PMID- 28434506
TI  - Jean-Andre Rochoux (1787-1852), a physician philosopher at the dawn of vascular
      neurology.
AB  - Jean-Andre Rochoux (1787-1852) can be considered the author, in 1812, of the
      first clinical and neuropathological description of cerebral hemorrhage and
      ischemia, based on concepts that underlie current vascular neurology. His
      biography reveals how his thinking was shaped by materialist philosophy, which
      was also the basis of his rigorous scientific reasoning. Due to his intransigent
      defence of his philosophical ideas and his outspoken anticlericalism, he was
      often contradicted and had many opponents who were not inclined to perpetuate his
      memory after his death, despite the high quality of his medical research. Our
      biography traces the career of this iconoclastic thinker and physician ahead of
      his time.

PMID- 28434507
TI  - Motor neuropathies and lower motor neuron syndromes.
AB  - Motor or motor-predominant neuropathies may arise from disease processes
      affecting the motor axon and/or its surrounding myelin. Lower motor neuron
      syndrome (LMNS) arises from a disease process affecting the spinal motor neuron
      itself. The term LMNS is more generally used, rather than motor neuronopathy,
      although both entities are clinically similar. Common features are muscle
      weakness (distal or proximal) with atrophy and hyporeflexia, but no sensory
      involvement. They can be acquired or hereditary. Immune-mediated neuropathies
      (multifocal motor neuropathy, motor-predominant chronic inflammatory
      demyelinating polyneuropathy) are important to identify, as effective treatments
      are available. Other acquired neuropathies, such as infectious, paraneoplastic
      and radiation-induced neuropathies are also well known. Focal LMNS is an
      amyotrophic lateral sclerosis (ALS)-mimicking syndrome especially affecting young
      adults. The main hereditary LMNSs in adulthood are Kennedy's disease, late-onset
      spinal muscular atrophy and distal hereditary motor neuropathies. Motor
      neuropathies and LMNS are all clinical entities that should be better known,
      despite being rare diseases. They can sometimes be difficult to differentially
      diagnose from other diseases, particularly from the more frequent ALS in its pure
      LMN form. Nevertheless, correct identification of these syndromes is important
      because their treatment and prognoses are definitely different.

PMID- 28434508
TI  - Immune Biomarkers on the Radar-Comprehensive "Immunograms" for Multimodal
      Treatment Prediction.

PMID- 28434509
TI  - Lonely Driver ROS1.

PMID- 28434510
TI  - PD-L1 Testing for Immune Checkpoint Inhibitors in Mesothelioma: For Want of
      Anything Better?

PMID- 28434511
TI  - Erratum.

PMID- 28434512
TI  - Harmonization of PD-L1 Immunohistochemistry Assays for Lung Cancer: A Working
      Progress.

PMID- 28434513
TI  - Severe Aplastic Anemia during Osimertinib Therapy in a Patient with EGFR Tyrosine
      Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.

PMID- 28434514
TI  - Cutaneous Toxicity Induced by Hibiscus Tea in a Patient Treated with Erlotinib.

PMID- 28434515
TI  - Multiple Acquired Resistance Mutations of the ALK Tyrosine Kinase Domain after
      Sequential Use of ALK Inhibitors.

PMID- 28434516
TI  - Long-Lasting Response to Nivolumab and Immune-Related Adverse Events in a
      Nonsquamous Metastatic Non-Small Cell Lung Cancer Patient.

PMID- 28434517
TI  - ALK-Rearranged Squamous Cell Carcinoma of the Lung Treated with Two Lines of ALK
      Inhibitors.

PMID- 28434518
TI  - Treatment of Bronchial Carcinoid Tumors: Is Surgery Really Necessary?

PMID- 28434519
TI  - The Relationship between Histology, Stage, and Type of Treatment in Patients with
      Early-Stage Lung Cancer.

PMID- 28434520
TI  - Successful Osimertinib Rechallenge in a Patient with T790M-Mutant Non-Small Cell
      Lung Cancer after Osimertinib-Induced Interstitial Lung Disease.

PMID- 28434522
TI  - Improving Nutrition Research in Nephrology: An Appetite for Change.

PMID- 28434521
TI  - Scoring Risk Scores: Considerations Before Incorporating Clinical Risk Prediction
      Tools Into Your Practice.

PMID- 28434524
TI  - Erratum Regarding "US Renal Data System 2016 Annual Data Report: Epidemiology of
      Kidney Disease in the United States" (Am J Kidney Dis. 2017;69[3][suppl 1]:Svii
      Sviii, S1-S668).

PMID- 28434523
TI  - Belatacept: Where the BENEFITS Outweigh the Risk.

PMID- 28434525
TI  - Quiz Page May 2017: CKD and Nephrotic Syndrome After Allogeneic Hematopoietic
      Cell Transplantation.

PMID- 28434526
TI  - AJKD Atlas of Renal Pathology: Calcineurin Inhibitor Nephrotoxicity.

PMID- 28434527
TI  - AJKD Atlas of Renal Pathology: Kidney Transplant Interstitial Fibrosis/Tubular
      Atrophy.

PMID- 28434528
TI  - Canine Hip Dysplasia Screening Within the United States: Pennsylvania Hip
      Improvement Program and Orthopedic Foundation for Animals Hip/Elbow Database.
AB  - Canine hip dysplasia (CHD) is a complex, polygenic disease radiographically
      associated with hip subluxation and development of osteoarthritis. Screening
      programs have been established with the goal of hip improvement, with the most
      common in the United States being OFA hip scoring and the PennHIP method. When
      evaluating the single hip-extended view used by OFA versus the 3 radiographic
      views and associated distraction index (DI) used by PennHIP for CHD screening,
      the scientific evidence supports the use of the DI and PennHIP method. OFA
      scoring can be used to effect hip improvement, especially when incorporated into
      estimated breeding values.

PMID- 28434529
TI  - Stochastic multicomponent reactive transport analysis of low quality drainage
      release from waste rock piles: Controls of the spatial distribution of acid
      generating and neutralizing minerals.
AB  - In mining environmental applications, it is important to assess water quality
      from waste rock piles (WRPs) and estimate the likelihood of acid rock drainage
      (ARD) over time. The mineralogical heterogeneity of WRPs is a source of
      uncertainty in this assessment, undermining the reliability of traditional bulk
      indicators used in the industry. We focused in this work on the bulk neutralizing
      potential ratio (NPR), which is defined as the ratio of the content of non-acid
      generating minerals (typically reactive carbonates such as calcite) to the
      content of potentially acid-generating minerals (typically sulfides such as
      pyrite). We used a streamtube-based Monte-Carlo method to show why and to what
      extent bulk NPR can be a poor indicator of ARD occurrence. We simulated ensembles
      of WRPs identical in their geometry and bulk NPR, which only differed in their
      initial distribution of the acid generating and acid neutralizing minerals that
      control NPR. All models simulated the same principal acid-producing, acid
      neutralizing and secondary mineral forming processes. We show that small
      differences in the distribution of local NPR values or the number of flow paths
      that generate acidity strongly influence drainage pH. The results indicate that
      the likelihood of ARD (epitomized by the probability of occurrence of pH<4 in a
      mixing boundary) within the first 100years can be as high as 75% for a NPR=2 and
      40% for NPR=4. The latter is traditionally considered as a "universally safe"
      threshold to ensure non-acidic waters in practical applications. Our results
      suggest that new methods that explicitly account for mineralogical heterogeneity
      must be sought when computing effective (upscaled) NPR values at the scale of the
      piles.

PMID- 28434530
TI  - Accelerated cellular senescence as underlying mechanism for functionally impaired
      bone marrow-derived progenitor cells in ischemic heart disease.
AB  - BACKGROUND AND AIMS: Bone marrow (BM)-derived progenitor cells are functionally
      impaired in patients with ischemic heart disease (IHD), thereby hampering the
      outcome of autologous stem cell therapy. In search for underlying mechanisms for
      this BM dysfunction, accelerated cellular senescence was explored. METHODS: We
      analysed telomere length of BM-derived mononuclear cells (MNC) by MMqPCR in
      patients with coronary artery disease (n = 12), ischemic heart failure (HF; n =
      9), non-ischemic HF (n = 7) and controls (n = 10), and related it to their
      myeloid differentiation capacity. Expressions of senescence-associated genes p53,
      p21Cip1 and p16lnk4A; and telomere maintenance genes TERT, TRF1/2, Sirt1 in BM
      MNC were evaluated using qPCR. Pro-inflammatory cytokine levels (TNFalpha, IFNy,
      IL-6) in BM were measured by MSD. RESULTS: BM-MNC telomere length was shortened
      in patients with IHD, irrespective of associated cardiomyopathy, and shortened
      further with increasing angiographic lesions. This telomere shortening was
      associated with reduced myeloid differentiation capacity of BM-MNC, suggesting
      accelerated senescence as underlying cause for progenitor cell dysfunction in
      IHD. Both p16lnk4A and p21Cip1 were activated in IHD and inversely related to
      myeloid differentiation capacity of BM-MNC; hence, the BM-MNC functional
      impairment worsens with increasing senescence. While BM-MNC telomere attrition
      was not related with alterations in TERT, TRF1/2 and Sirt1 expression, IFNy
      levels were associated with p21Cip1/p16lnk4A upregulation, suggesting a link
      between inflammation and cellular senescence. Still, the trigger for telomere
      shortening in IHD needs to be elucidated. CONCLUSIONS: Accelerated replicative
      senescence is associated with a functional impairment of BM-derived progenitor
      cells in IHD and could be targeted to improve efficacy of stem cell therapy.

PMID- 28434531
TI  - Surface properties of magnetite in high temperature aqueous electrolyte
      solutions: A review.
AB  - Deposits and scales formed on heat transfer surfaces in power plant water/steam
      circuits have a significant negative impact on plant reliability, availability
      and performance, causing tremendous economic consequences and subsequent
      increases in electricity cost. Consequently, the improvement of the understanding
      of deposition mechanisms on power generating surfaces is defined as a high
      priority in the power industry. The deposits consist principally of iron oxides,
      which are steel corrosion products and usually present in colloidal form.
      Magnetite (Fe3O4) is the predominant and most abundant compound found in
      water/steam cycles of all types of power plants. The crucial factor that governs
      the deposition process and influences the deposition rate of magnetite is the
      electrostatic interaction between the metal wall surfaces and the suspended
      colloidal particles. However, there is scarcity of data on magnetite surface
      properties at elevated temperatures due to difficulties in their experimental
      measurement. In this paper a generalized overview of existing experimental data
      on surface characteristics of magnetite at high temperatures is presented with
      particular emphasis on possible application in the power industry. A thorough
      analysis of experimental techniques, mathematical models and results has been
      performed and directions for future investigations have been considered. The
      state-of-the-art assessment showed that for the characterization of
      magnetite/aqueous electrolyte solution interface at high temperatures acid-base
      potentiometric titrations and electrophoresis were the most beneficial and
      dependable techniques which yielded results up to 290 and 200 degrees C,
      respectively. Mass titrations provided data on magnetite surface charge up to 320
      degrees C, however, this technique is highly sensitive to the minor
      concentrations of impurities present on the surface of particle. Generally,
      fairly good correlation between the isoelectric point (pHiep) and point of zero
      charge (pHpzc) values has been obtained. All obtained results showed that the
      surface of magnetite particles is negatively charged in typical high temperature
      thermal power plant water, which indicates the low probability of aggregation and
      deposition on plant metal surfaces. The results also gave strong evidence on
      decline of pHiep and pHpzc with temperature in the same manner as neutral pH of
      water. The thermodynamic parameters of magnetite surface protonation reactions
      were in good agreement with each other and obtained using one site/two pK and
      mainly one site/one pK model. All collected data provided evidences for
      interaction between particles, probability of deposition and eventual attachment
      to the steel surface at various pH and temperatures and can serve as a foundation
      for future surface studies aimed at optimizing plant performances and reducing of
      magnetite deposition. In future works it would be indispensable to provide the
      surface experimental data for extended temperature ranges, typical solution
      chemistries and metal surfaces of power plant structural components and thus
      obtain entire set of results useful in modeling the surface behavior and control
      of deposition process in power reactors and thermal plant circuits. Moreover, the
      acquired results will be applicable and greatly valuable to all other types of
      power plants, industrial facilities and technological processes using the high
      temperature water medium.

PMID- 28434532
TI  - Total parenteral nutrition usage trends in the United States.
AB  - INTRODUCTION: This study examined how total parenteral nutrition (TPN) usage has
      changed in recent years, and whether a difference exists between teaching and non
      teaching institutions. MATERIALS AND METHODS: Using the National Inpatient Sample
      (NIS) database, total discharges of patients who received TPN (ICD-9 99.15) from
      2001 to 2014 were determined. The cohort was dichotomized for teaching and non
      teaching institutions, and analyzed using the Z-test statistic. RESULTS: Annual
      patients receiving TPN at all institutions increased significantly from 25,075 in
      2001 to 33,435 in 2014 (P<0.0001), peaking at 43,350 in 2012. Annual patients
      receiving TPN at teaching institutions increased significantly from 13,231 in
      2001 to 24,630 in 2014 (P<0.0001), peaking at 26,935 in 2012. Annual patients
      receiving TPN at non-teaching institutions decreased significantly from 11,844 in
      2001 to 8805 in 2014 (P<0.0001), peaking at 17,920 in 2011. DISCUSSION: It is
      unclear why TPN usage trended upward in United States hospitals, and why TPN
      usage peaked and subsequently decreased in non-teaching institutions while
      continuing to uptrend in teaching institutions. Further inquiry is indicated to
      determine the etiology of this discrepancy. CONCLUSIONS: Utilization of TPN
      increased in the United States between 2001 and 2014, eventually decreasing in
      non-teaching institutions but not in teaching institutions.

PMID- 28434533
TI  - Performance of Fixed Heart Rate Increment Targets of 20 vs 30 Beats per Minute
      for Exercise Rehabilitation Prescription in Outpatients With Heart Failure.
AB  - BACKGROUND: Patients with heart failure (HF) should exercise at 40%-60% heart
      rate reserve (HRR) during the first 3 weeks of an outpatient cardiac
      rehabilitation (CR) program and at 50%-80% HRR thereafter. Arbitrary methods to
      prescribe exercise intensity such as resting HR (RHR) plus 20 or 30 beats per
      minute (bpm) (RHR + 20 or RHR + 30) are recommended for inpatients after a
      myocardial infarction or those recovering from heart surgery. This approach has
      been repurposed by outpatient CR programs to prescribe exercise intensity for
      patients with HF, yet its efficacy has not been evaluated. METHODS: We examined
      the appropriateness of RHR + 20/30 for prescribing exercise intensity and
      improving functional capacity for 55 patients with HF in an outpatient CR
      program. RHR + 20/30 values were compared to % HRR derived from peak exercise
      testing in patients with HF. Changes in functional capacity as measured by 6
      minute walk test (6MWT) distance, and differences in ratings of perceived
      exertion (RPE), were examined between patients exercising at RHR + 20-29 and
      those exercising at RHR + >= 30. RESULTS: During weeks 1-3 and exercise at RHR +
      20, 26% of participants would exercise at 40%-60% HRR. At RHR + 30, 38% would
      exercise at 40%-60% HRR. During weeks 4-12 and exercise at RHR + 20, 20% of
      participants would exercise at 50%-80% HRR. At RHR + 30, 41% would exercise at
      50%-80% HRR. A smaller change in 6MWT distance was observed in participants
      exercising at RHR + 20-29 than in those exercising at RHR + >= 30 (Delta86.6 +/-
      70.3 vs Delta135.8 +/- 73.7 m; P = 0.005). No differences in RPE were observed
      between participants exercising at RHR + 20-29 and those exercising at RHR + >=
      30 (P > 0.05). CONCLUSIONS: RHR + 30 was more effective than RHR + 20 in
      assisting outpatients with HF achieve recommended exercise intensities and
      improve functional capacity.

PMID- 28434534
TI  - Comparative analysis of trabecular bone structure and orientation in South
      African hominin tali.
AB  - Tali of several hominin taxa are preserved in the fossil record and studies of
      the external morphology of these often show a mosaic of human-like and ape-like
      features. This has contributed to a growing recognition of variability
      characterizing locomotor kinematics of Australopithecus. In contrast, locomotor
      kinematics of another Plio-Pleistocene hominin, Paranthropus, are substantially
      less well-documented, in part, because of the paucity of postcranial fossils
      securely attributed to the genus. Since the talus transmits locomotor-based loads
      through the ankle and its internal structure is hypothesized to reflect
      accommodation to such loads, it is a cornerstone structure for reconstructing
      locomotor kinematics. Here we quantify and characterize trabecular bone
      morphology within tali attributed to Australopithecus africanus (StW 102, StW
      363, StW 486) and Paranthropus robustus (TM 1517), making quantitative
      comparisons to modern humans, extant non-human apes, baboons, and a hominin talus
      attributed to Paranthropus boisei (KNM-ER 1464). Using high-resolution images of
      fossil tali (25 MUm voxels), nine trabecular bone subregions of interest beneath
      the articular surface of the talar trochlea were segmented to quantify localized
      patterns in distribution and primary strut orientation. It was found that
      trabecular strut orientation and shape, in some cases, can discriminate amongst
      species characterized by different locomotor foot kinematics. Discriminant
      function analyses using standard trabecular bone structural properties align TM
      1517 with Pan and Gorilla, while other hominin tali structurally most resemble
      those of baboons. In primary strut orientation, Paranthropus tali (KNM-ER 1464
      and TM 1517) resemble the human condition in the anterior-medial subregion, where
      strut orientation appears positioned to distribute compressive loads medially and
      distally toward the talar head. In A. africanus tali (particularly StW 486),
      primary strut orientation in this region resembles that of apes. These results
      suggest that Paranthropus may have had a human-like medial weight shift during
      the last half of stance phase but Australopithecus did not.

PMID- 28434535
TI  - Fruits of the forest: Human stable isotope ecology and rainforest adaptations in
      Late Pleistocene and Holocene (~36 to 3 ka) Sri Lanka.
AB  - Sri Lanka has yielded some of the earliest dated fossil evidence for Homo sapiens
      (~38-35,000 cal. years BP [calibrated years before present]) in South Asia,
      within a region that is today covered by tropical rainforest. Archaeozoological
      and archaeobotanical evidence indicates that these hunter-gatherers exploited
      tropical forest resources, yet the contribution of these resources to their
      overall subsistence strategies has, as in other Late Pleistocene rainforest
      settings, remained relatively unexplored. We build on previous work in this
      tropical region by applying both bulk and sequential stable carbon and oxygen
      isotope analysis to human and faunal tooth enamel from the sites of Batadomba
      lena, Fa Hien-lena, and Balangoda Kuragala. Tooth enamel preservation was
      assessed by means of Fourier Transform Infrared Spectroscopy. We use these data
      to produce a detailed stable isotope ecology for Late Pleistocene-Holocene
      foragers in Sri Lanka from ~36-29,000 to 3000 cal. years BP, allowing us to test
      the degree of human tropical forest resource reliance over a considerable time
      period. Given that non-human primates dominate the mammalian assemblages at these
      sites, we also focus on the stable isotope composition of three monkey species in
      order to study their ecological preferences and, indirectly, human hunting
      strategies. The results confirm a strong human reliance on tropical forest
      resources from ~36-29,000 cal. years BP until the Iron Age ~3 cal. years BP,
      while sequential tooth data show that forest resources were exploited year-round.
      This strategy was maintained through periods of evident environmental change at
      the Last Glacial Maximum and upon the arrival of agriculture. Long-term tropical
      forest reliance was supported by the specialised capture of non-human primates,
      although the isotopic data revealed no evidence for niche distinction between the
      hunted species. We conclude that humans rapidly developed a specialisation in the
      exploitation of South Asia's tropical forests following their arrival in this
      region.

PMID- 28434536
TI  - Scaling of rotational inertia of primate mandibles.
AB  - The relative importance of pendulum mechanics and muscle mechanics in chewing
      dynamics has implications for understanding the optimality criteria driving the
      evolution of primate feeding systems. The Spring Model (Ross et al., 2009b),
      which modeled the primate chewing system as a forced mass-spring system,
      predicted that chew cycle time would increase faster than was actually observed.
      We hypothesized that if mandibular momentum plays an important role in chewing
      dynamics, more accurate estimates of the rotational inertia of the mandible would
      improve the accuracy with which the Spring Model predicts the scaling of primate
      chew cycle period. However, if mass-related momentum effects are of negligible
      importance in the scaling of primate chew cycle period, this hypothesis would be
      falsified. We also predicted that greater "robusticity" of anthropoid mandibles
      compared with prosimians would be associated with higher moments of inertia. From
      computed tomography scans, we estimated the scaling of the moment of inertia (Ij)
      of the mandibles of thirty-one species of primates, including 22 anthropoid and
      nine prosimian species, separating Ij into the moment about a transverse axis
      through the center of mass (Ixx) and the moment of the center of mass about
      plausible axes of rotation. We found that across primates Ij increases with
      positive allometry relative to jaw length, primarily due to positive allometry of
      jaw mass and Ixx, and that anthropoid mandibles have greater rotational inertia
      compared with prosimian mandibles of similar length. Positive allometry of Ij of
      primate mandibles actually lowers the predictive ability of the Spring Model,
      suggesting that scaling of primate chew cycle period, and chewing dynamics in
      general, are more strongly influenced by factors other than scaling of inertial
      properties of the mandible, such as the dynamic properties of the jaw muscles and
      neural control. Differences in cycle period scaling between chewing and
      locomotion systems reinforce the suggestion that displacement and force control
      are more important in the design of feeding systems than energetics and speed.

PMID- 28434537
TI  - New cranium of the endemic Caribbean platyrrhine, Antillothrix bernensis, from La
      Altagracia Province, Dominican Republic.
AB  - Recent paleontological collection in submerged caves in the eastern Dominican
      Republic has yielded new specimens of Antillothrix bernensis. Here we describe a
      complete cranium of an adult individual (MHD 20) and provide phenetic comparisons
      to other endemic Caribbean taxa and extant mainland platyrrhines using three
      dimensional geometric morphometric methods (3DGM). Qualitative and quantitative
      comparisons support conclusions based on other recently described fossil
      material: Antillothrix has a dentition lacking clear dietary specialization, an
      elongated brain case with strong temporal lines, and a vertically oriented nuchal
      plane. MHD 20 shares a combination of traits with a previously published subadult
      specimen (MHD 01) including a deep depression at glabella, dorsoventrally
      elongated orbits, and a relatively large face. This shared morphology reinforces
      the taxonomic affinity of the two specimens, with differences between the two
      likely reflecting the younger ontogenetic age of MHD 01. Comparisons to the
      extant platyrrhines paint a complicated picture as the results of between-group
      principal components analyses (bgPCA) indicate that Antillothrix does not share a
      suite of morphological features exclusively with any one genus. Depending on
      which bgPC axes are visualized, and which subset of landmarks is included (i.e.,
      only those describing the shape of the face/palate for inclusion of Xenothrix),
      MHD 20 is most similar in shape to the atelids, Alouatta, Lagothrix, and
      Brachyteles, or an otherwise "empty" region of shape space. It groups neither
      with Cebus nor Callicebus, two taxa that Antillothrix has been associated with in
      previous studies based on much less complete material. The Antillothrix cranium
      does not exhibit any of the derived characters classically used to diagnose or
      define any single clade; rather its morphology shares features with multiple
      platyrrhine groups. This is consistent with the interpretation that Antillothrix
      preserves a primitive morphology, which accords with the hypothesis positing an
      early arrival of platyrrhines in the Caribbean.

PMID- 28434538
TI  - Thinking locally: Environmental reconstruction of Middle and Later Stone Age
      archaeological sites in Ethiopia, Kenya, and Zambia based on ungulate stable
      isotopes.
AB  - Our knowledge of the Pleistocene environments of Africa consists primarily of
      data at a scale too coarse to capture the full habitat variation important to
      hominins 'on the ground.' These environments are complex, highly variable, and
      poorly understood. As such, data from individual sites are a needed addition to
      our current paleoenvironmental reconstructions. This study offers a site-based
      approach focusing on stable isotope analyses of fossil faunal tooth enamel from
      three archaeological sites in tropical Africa. Carbon and oxygen stable isotope
      data are reported from the sites of Porc Epic, Ethiopia, Lukenya Hill, Kenya, and
      Kalemba Rockshelter, Zambia. Stable isotope data from tooth enamel are used to
      measure two environmental variables: (1) aridity based on oxygen isotope
      composition and (2) dietary reconstructions of fossil ungulates based on the
      relative proportions of C3 browse and C4 graze in the diet. These data allow for
      a preliminary assessment of existing models that attempt to explain the
      behavioral and technological variation characteristic of the transition between
      the Middle and Later Stone Ages. Results indicate spatial and temporal variation
      in aridity and phytogeography in tropical Africa during the Pleistocene,
      suggesting that no single model is likely to provide an explanation for the
      transition at all sites across Africa.

PMID- 28434539
TI  - Evolutionary anatomy of the Neandertal ulna and radius in the light of the new El
      Sidron sample.
AB  - This paper aims to improve our understanding of the phylogenetic trait polarity
      related to hominin forearm evolution, in particular those traits traditionally
      defined as "Neandertal features." To this aim, twelve adult and adolescent
      fragmented forelimb elements (including ulnae and radii) of Homo neanderthalensis
      recovered from the site of El Sidron (Asturias, Spain) were examined
      comparatively using three-dimensional geometric and traditional morphometrics.
      Mean centroid size and shape comparisons, principal components analysis, and
      phylogenetic signal analysis were undertaken. Our investigations revealed that
      the proximal region of the ulna discriminated best between Neandertals and modern
      humans, with fewer taxonomically-informative features in the distal ulna and
      radius. Compared to modern humans, the divergent features in the Neandertal ulna
      are an increase in olecranon breadth (a derived trait), lower coronoid length
      (primitive), and anterior orientation of the trochlear notch (primitive). In the
      Neandertal radius, we observe a larger neck length (primitive), medial
      orientation of the radial tubercle (secondarily primitive), and a curved
      diaphysis (secondarily primitive). Anatomically, we identified three units of
      evolutionary change: 1) the olecranon and its fossa, 2) the coronoid-radius neck
      complex, and 3) the tubercle and radial diaphysis. Based on our data, forearm
      evolution followed a mosaic pattern in which some features were inherited from a
      pre-Homo ancestor, others originated in some post-ergaster and pre-antecessor
      populations, and other characters emerged in the specific Homo sapiens and H.
      neanderthalensis lineages, sometimes appearing as secondarily primitive. Future
      investigations might consider the diverse phylogenetic origin of apomorphies
      while at the same time seeking to elucidate their functional meaning.

PMID- 28434540
TI  - An updated age for the Xujiayao hominin from the Nihewan Basin, North China:
      Implications for Middle Pleistocene human evolution in East Asia.
AB  - The Xujiayao site in the Nihewan Basin (North China) is one of the most important
      Paleolithic sites in East Asia. Twenty Homo fossils, which were previously
      assigned to an archaic Homo sapiens group, have been excavated along with more
      than 30,000 lithic artifacts and ~5000 mammalian fossil specimens. Dating of the
      Xujiayao hominin has been pursued since its excavation in the 1970s, but its age
      has remained controversial because of limitations of the dating techniques that
      have been applied to available materials. Here, we report new ages for the
      Xujiayao hominin based on combined electron spin resonance (ESR) dating of quartz
      in the sediments and high-resolution magnetostratigraphy of the fluvio-lacustrine
      sequence. The magnetostratigraphy suggests that the upper Matuyama and Brunhes
      polarity chrons are recorded at Xujiayao. The ESR dating results indicate a
      pooled average age of 260-370 ka for the Homo-bearing layer, which is consistent
      with its position within the middle Brunhes normal polarity chron indicated by
      magnetostratigraphy. This age estimate makes the Xujiayao hominin among the
      oldest mid-Pleistocene hominins with derived Neanderthal traits in East Asia.
      This age is consistent with the time when early Denisovans, a sister group of
      Neanderthals, appeared and colonized eastern Eurasia. Our updated age and the
      Neanderthal-like traits of the Xujiayao Homo fossils, particularly the Denisovan
      like molar teeth, make it possible that the Xujiayao hominin could represent an
      early Denisovan.

PMID- 28434541
TI  - Phytoliths indicate significant arboreal cover at Sahelanthropus type locality
      TM266 in northern Chad and a decrease in later sites.
AB  - We analyzed phytolith and diatom remains preserved at 45 Miocene and Pliocene
      localities dated between 8 and 1 Ma in northern Chad (16-17 degrees N). Some of
      these localities yielded cranial remains, lower jaws, and teeth of the hominin
      species Australopithecus bahrelghazali (~3.6 Ma) and Sahelanthropus tchadensis
      (~7 Ma). Of the 111 sediment samples analyzed, 41 yielded phytoliths, 20 yielded
      diatoms, and seven yielded both phytoliths and diatoms. Freshwater planktonic and
      tychoplanktonic diatom species, indicative of lacustrine conditions, are dominant
      (>91%) in the samples. The phytolith assemblages indicate an opening of the
      vegetation and a general trend toward an expansion of grass-dominated
      environments during the time spanning the two hominin occurrences in Chad. The
      phytoliths suggest the presence of a mosaic environment, including closed forest
      patches, palm groves, and mixed/grassland formations, between 7.5 and 7 Ma, the
      replacement by palm grove-like vegetation at approximately 6.5-5 Ma, and the
      presence of exclusive grass-dominated formations after 4.5 Ma. The type-locality
      of S. tchadensis (TM266) was likely similar to modern palm grove formations with
      an arboreal cover percentage >=40%. The type locality of A. bahrelghazali (KT12)
      was a grass-dominated ecosystem (likely savanna) with an unrated percentage of
      arboreal cover. Furthermore, the grass phytolith data support the existence of a
      (recurrent) Sahelian-like dry climate in northern Chad since at least 8 Ma.
      Therefore the local closed vegetation formations in the Djurab region at 7.5-7 Ma
      were sustained by aquatic systems (such as lakes or related rivers, marshes)
      rather than by extensive annual precipitation.

PMID- 28434542
TI  - The Neandertal vertebral column 2: The lumbar spine.
AB  - Here we provide the most extensive metric and morphological analysis performed to
      date on the Neandertal lumbar spine. Neandertal lumbar vertebrae show differences
      from modern humans in both the vertebral body and in the neural arch, although
      not all Neandertal lumbar vertebrae differ from modern humans in the same way.
      Differences in the vertebral foramen are restricted to the lowermost lumbar
      vertebrae (L4 and L5), differences in the orientation of the upper articular
      facets appear in the uppermost lumbar vertebrae (probably in L1 and L2-L3), and
      differences in the horizontal angle of the transverse process appear in L2-L4.
      Neandertals, when compared to modern humans, show a smaller degree of lumbar
      lordosis. Based on a still limited fossil sample, early hominins (australopiths
      and Homo erectus) had a lumbar lordosis that was similar to but below the mean of
      modern humans. Here, we hypothesize that from this ancestral degree of lumbar
      lordosis, the Neandertal lineage decreased their lumbar lordosis and Homo sapiens
      slightly increased theirs. From a postural point of view, the lower degree of
      lordosis is related to a more vertical position of the sacrum, which is also
      positioned more ventrally with respect to the dorsal end of the pelvis. This
      results in a spino-pelvic alignment that, though different from modern humans,
      maintained an economic postural equilibrium. Some features, such as a lower
      degree of lumbar lordosis, were already present in the middle Pleistocene
      populations ancestral to Neandertals. However, these middle Pleistocene
      populations do not show the full suite of Neandertal lumbar morphologies, which
      probably means that the characteristic features of the Neandertal lumbar spine
      did not arise all at once.

PMID- 28434543
TI  - Predatory Publishing in Rehabilitation.

PMID- 28434544
TI  - Correction.

PMID- 28434545
TI  - Opportunities and obstacles in translating evidence to policy in occupational
      asthma.
AB  - PURPOSE: Occupational asthma (OA), a common respiratory disorder in Western
      countries, is caused by exposures at the workplace. It is part of a broader
      definition of work-related asthma (WRA) that also includes pre-existing asthma
      aggravated by substances present in the workplace environment, and it is
      potentially preventable. The purpose of this paper is to illustrate preventive
      measures for occupational asthma by case studies. METHODS: In three case studies
      we discuss preventive measures that have been associated with reductions in
      incidence of occupational asthma from natural rubber latex and from diisocyanates
      as supported by published literature. We also discuss challenges in relation to
      asthma from cleaning products in healthcare work. RESULTS AND CONCLUSIONS:
      Several preventive measures have been associated with reduction in incidence of
      occupational asthma from natural rubber latex and from diisocyanates, and may
      provide lessons for prevention of other causes of occupational asthma. Cleaning
      products remain an unresolved problem at present with respect to asthma risks but
      potential measures include the use of safer products and safer applications such
      as avoidance of spray products, use of occupational hygiene methods such as
      improving local ventilation, and when appropriate, the use of personal protective
      devices.

PMID- 28434546
TI  - Surgical Strategy Toward Biventricular Repair for Severe Ebstein Anomaly in
      Neonates and Infancy.
AB  - BACKGROUND: Neonates with severe forms of Ebstein anomaly present a surgical
      challenge, and the Starnes operation as single ventricle palliation is highly
      advocated. Cone reconstruction for tricuspid valvuloplasty (TVP) has become a
      widely accepted technique, although very few cases of TVP have been reported in
      neonates. This report describes a surgical strategy for neonatal Ebstein anomaly,
      with an aim toward biventricular repair. METHODS: Since 2007, 7 neonates or young
      infants with severe Ebstein anomalies have received TVP at the National Taiwan
      University Hospital, Taipei, Taiwan. The principle of cone reconstruction was
      applied with mobilization of all three leaflets and reattachment to the normal
      tricuspid annulus. The atrialized right ventricle was not plicated. In patients
      with pulmonary stenosis, the interatrial communication was not totally closed (n
      = 5), and a systemic-pulmonary shunt was added if needed (n = 3). RESULTS: All
      patients presented with intractable heart failure or severe cyanosis requiring
      mechanical ventilation, or both. All patients had marked adherence of the
      anterior leaflet to the right ventricular free wall. Intracardiac anomalies
      including ventricular septal defect (n = 2) and tetralogy of Fallot (n = 1) were
      also repaired simultaneously. Six of the 7 patients (86%) survived. There were no
      late deaths or repeat TVPs for a median follow-up of 4.3 years (range, 0.8 to 9.9
      years). CONCLUSIONS: Reconstruction of the tricuspid valve is an acceptable
      surgical strategy in patients with severe neonatal Ebstein anomaly. Fenestrated
      atrial septal defect and systemic-pulmonary shunt can help overcome anatomic
      pulmonary stenosis and high pulmonary resistance in the neonatal period. This
      surgical strategy has a good survival outcome and preserves the possibility of
      complete biventricular repair.

PMID- 28434547
TI  - Stress-Dose Corticosteroid Versus Placebo in Neonatal Cardiac Operations: A
      Randomized Controlled Trial.
AB  - BACKGROUND: Corticosteroids can improve the hemodynamic status of neonates with
      postoperative low cardiac output syndrome after cardiac operations. This study
      compared a prophylactically administered stress-dose corticosteroid (SDC) regimen
      against placebo on inflammation, adrenocortical function, and hemodynamic
      outcome. METHODS: Forty neonates undergoing elective open heart operations were
      randomized into two groups. The SDC group received perioperatively 2 mg/kg
      methylprednisolone, and 6 hours after the operation, a hydrocortisone infusion
      (0.2 mg/kg/h) was started with tapering doses for 5 days. Placebo was
      administered in a similar fashion. An adrenocorticotropic hormone stimulation
      test was performed after the therapy. The primary endpoint of the study was
      plasma concentration of interleukin (IL-6). Secondary clinical outcomes included
      plasma cortisol, IL-10, C-reactive protein, echocardiographic systemic ventricle
      contractility evaluated by the Velocity Vector Imaging program, the inotropic
      score, and time of delayed sternal closure. RESULTS: The IL-6 values of the SDC
      group were significantly lower postoperatively than in the placebo group.
      Significantly lower inotropic scores (p < 0.05), earlier sternal closure (p =
      0.03), and less deterioration in the systemic ventricle mean delta strain values
      between the preoperative and the first postoperative assessment (p = 0.01) were
      detected for the SDC group. The SDC therapy did not suppress the hypothalamic
      pituitary-adrenal axis more than placebo. The mean plasma cortisol level did not
      decline in the placebo group after the operation. CONCLUSIONS: The SDC regimen
      for 5 days postoperatively in neonates was safe and did not cause suppression of
      the hypothalamic-pituitary-adrenal axis. Furthermore, the open heart operation
      per se did not lead to adrenal insufficiency in neonates.

PMID- 28434548
TI  - Ex Vivo Lung Perfusion Rehabilitates Sepsis-Induced Lung Injury.
AB  - BACKGROUND: Sepsis is the number one cause of lung injury in adults. Ex vivo lung
      perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and
      rehabilitation and may expand the use of marginal organs for transplantation. We
      hypothesized that 4 hours of normothermic EVLP would improve compliance and
      oxygenation in a porcine model of sepsis-induced lung injury. METHODS: We used
      intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response
      in a porcine model of lung injury. Two groups of 4 animals each received a 2-hour
      infusion of LPS through the external jugular vein. Serial measurements of blood
      gases were performed every 30 minutes until the partial pressure of
      oxygen/fraction of inspired oxygen ratio dropped below 150 on two consecutive
      readings. Lungs were then randomized to treatment with 4 hours of normothermic
      EVLP with STEEN Solution (XVIVO Perfusion Inc, Englewood, CO) or 4 additional
      hours of in vivo perfusion (control). Airway pressures and blood gases were
      recorded for calculation of dynamic lung compliance and partial pressure of
      oxygen/fraction of inspired oxygen ratios. EVLP was performed with hourly
      recruitment maneuvers and oxygen challenge. RESULTS: All animals reached a
      partial pressure of oxygen/fraction of inspired oxygen ratio of less than 150 mm
      Hg within 3 hours after start of the LPS infusion. Oxygenation and compliance in
      the control animals continued to decline during the 4-hour in vivo perfusion
      period, and 3 of the 4 animals died of severe hypoxia within 4 hours. The EVLP
      group demonstrated significant improvements hour 1 to hour 4 in oxygenation
      (365.8 +/- 53.0 vs 584.4 +/- 21.0 mm Hg, p = 0.02) and dynamic compliance (9.0 +/
      2.8 vs 15.0 +/- 3.6, p = 0.02 mL/cm H2O). CONCLUSIONS: EVLP successfully
      rehabilitated LPS-induced lung injury in this preclinical porcine model and may
      thus provide a means to rehabilitate many types of acute lung injury.

PMID- 28434549
TI  - Systematic Review of Reintervention After Thoracic Endovascular Repair for
      Chronic Type B Dissection.
AB  - This review analyzed the incidence, mechanisms, and risk factors of aortic
      related reintervention after endovascular repair of chronic dissections. The
      systematic review identified 28 studies describing 1,249 patients at median 27
      months follow-up (range, 10.3 to 64.4). There were six reinterventions, 0.7
      ruptures, and 1.2 surgical conversions per 100 patient-years of follow-up. Stent
      related reinterventions were more frequent than nonstent related (80.2% vs
      19.8%). Distal false lumen perfusion was the most common complication (40.5%). No
      individual risk factor-treatment timing, disease extent, covered aorta length, or
      remodelling-was associated with reintervention. Further investigation based on
      consistent reporting standards is required.

PMID- 28434550
TI  - Renal Failure After Cardiac Operations: Not All Acute Kidney Injury Is the Same.
AB  - BACKGROUND: The Society of Thoracic Surgeons (STS) database does not distinguish
      between a decline in creatinine clearance vs new hemodialysis (HD) when
      qualifying acute renal failure (ARF) after a cardiac operation. We hypothesized
      that patients requiring HD experience significantly greater postoperative
      morbidity and death. METHODS: We included all patients who underwent STS index
      cardiac operations at our institution from 2008 to March 2015 and did not have
      preexisting renal failure (creatinine >4.0 mg/dL or preoperative HD). We
      identified patients meeting STS criteria for ARF: threefold rise in serum
      creatinine, creatinine exceeding 4.0 mg/dL (non-HD ARF) with minimum rise of 0.5
      mg/dL, or HD (ARF-HD). After propensity matching non-HD ARF and ARF-HD groups
      across 14 variables (including baseline glomerular filtration rate), we compared
      incidences of our primary outcome, death, and secondary outcomes, intensive care
      unit (ICU) and hospital length of stay (LOS), and discharge to a location other
      than home. RESULTS: Among 4,154 study patients, we identified 113 (2.7%) that
      experienced new-onset non-HD ARF (n = 57) or ARF-HD (n = 56) postoperatively.
      Propensity matching resulted in 51 well-matched pairs who experienced non-HD ARF
      or ARF-HD (all p > 0.10). Patients requiring HD suffered significantly greater
      operative mortality (67% vs 22%, p < 0.01), longer ICU LOS (326 vs 176 hours, p <
      0.01), and greater postoperative hospital LOS (34 vs 17 days, p < 0.01). ARF-HD
      patients also demonstrated a trend toward higher rates of discharge to a location
      other than home (71% vs 45%, p = 0.08). CONCLUSIONS: After cardiac operations,
      patients who experienced ARF-HD experienced triple the mortality and double the
      ICU and postoperative hospital LOS compared with patients who experienced non-HD
      ARF.

PMID- 28434551
TI  - Neuromuscular fatigue during exercise: Methodological considerations, etiology
      and potential role in chronic fatigue.
AB  - The term fatigue is used to describe a distressing and persistent symptom of
      physical and/or mental tiredness in certain clinical populations, with distinct
      but ultimately complex, multifactorial and heterogenous pathophysiology. Chronic
      fatigue impacts on quality of life, reduces the capacity to perform activities of
      daily living, and is typically measured using subjective self-report tools.
      Fatigue also refers to an acute reduction in the ability to produce maximal force
      or power due to exercise. The classical measurement of exercise-induced fatigue
      involves neuromuscular assessments before and after a fatiguing task. The
      limitations and alternatives to this approach are reviewed in this paper in
      relation to the lower limb and whole-body exercise, given the functional
      relevance to locomotion, rehabilitation and activities of daily living. It is
      suggested that under some circumstances, alterations in the central and/or
      peripheral mechanisms of fatigue during exercise may be related to the sensations
      of chronic fatigue. As such, the neurophysiological correlates of exercise
      induced fatigue are briefly examined in two clinical examples where chronic
      fatigue is common: cancer survivors and people with multiple sclerosis. This
      review highlights the relationship between objective measures of fatigability
      with whole-body exercise and perceptions of fatigue as a priority for future
      research, given the importance of exercise in relieving symptoms of chronic
      fatigue and/or overall disease management. As chronic fatigue is likely to be
      specific to the individual and unlikely to be due to a simple biological or
      psychosocial explanation, tailored exercise programmes are a potential target for
      therapeutic intervention.

PMID- 28434552
TI  - Re: The accuracy of interpretation of emergency abdominal CT in adult patients
      who present with non-traumatic abdominal pain: results of a UK national audit.

PMID- 28434553
TI  - Re: The accuracy of interpretation of emergency abdominal CT in adult patients
      who present with non-traumatic abdominal pain: results of a UK national audit. A
      reply.

PMID- 28434555
TI  - Phase 2 clinical trials with K-877 (pemafibrate): A promising selective PPAR
      alpha modulator for treatment of combined dyslipidemia.

PMID- 28434554
TI  - The Simulation-Based Assessment of Pediatric Rapid Response Teams.
AB  - OBJECTIVE: To create scenarios of simulated decompensating pediatric patients to
      train pediatric rapid response teams (RRTs) and to determine whether the scenario
      scores provide a valid assessment of RRT performance with the hypothesis that
      RRTs led by intensivists-in-training would be better prepared to manage the
      scenarios than teams led by nurse practitioners. STUDY DESIGN: A set of 10
      simulated scenarios was designed for the training and assessment of pediatric
      RRTs. Pediatric RRTs, comprising a pediatric intensive care unit (PICU)
      registered nurse and respiratory therapist, led by a PICU intensivist-in-training
      or a pediatric nurse practitioner, managed 7 simulated acutely decompensating
      patients. Two raters evaluated the scenario performances and psychometric
      analyses of the scenarios were performed. RESULTS: The teams readily managed
      scenarios such as supraventricular tachycardia and opioid overdose but had
      difficulty with more complicated scenarios such as aortic coarctation or head
      injury. The management of any particular scenario was reasonably predictive of
      overall team performance. The teams led by the PICU intensivists-in-training
      outperformed the teams led by the pediatric nurse practitioners. CONCLUSIONS:
      Simulation provides a method for RRTs to develop decision-making skills in
      managing decompensating pediatric patients. The multiple scenario assessment
      provided a moderately reliable team score. The greater scores achieved by PICU
      intensivist-in-training-led teams provides some evidence to support the validity
      of the assessment.

PMID- 28434556
TI  - CAD/CAM techniques help in the rebuilding of ideal marginal gingiva contours of
      anterior maxillary teeth: A case report.
AB  - BACKGROUND AND OVERVIEW: "Pink esthetics," which are considered to be as
      important as "white esthetics," have attracted increasing attention. To date,
      clinicians rarely have applied computer-aided design and computer-aided
      manufacturing (CAD/CAM) techniques in the rebuilding of the contour of the
      marginal gingiva in the esthetic zone. CASE DESCRIPTION: In this case report, the
      authors describe a female patient who had gingival inflammation and an
      asymmetrical contour of the marginal gingiva of the anterior maxillary teeth
      because previously placed ceramic crowns violated the biological width. The
      authors used a 3-dimensional-printing surgery template to guide precise crown
      lengthening surgery to expose subgingival shoulders and to obtain an ideal
      marginal gingival contour. Then the authors used interim CAD/CAM crowns to induce
      the growth of the interdental papilla by 0.5 to 1.5 millimeters. Finally, the
      patient had a symmetrical and well-balanced contour of the marginal gingiva. In
      addition, the authors reduced the patient's "black triangle" areas to the
      greatest possible extent. CONCLUSIONS AND PRACTICAL IMPLICATIONS: This case
      report illustrates that CAD/CAM products, including 3-dimensional-printing
      surgery templates and CAD/CAM interim crowns, are helpful in shaping and
      rebuilding the ideal contour of the marginal gingiva in the esthetic zone, such
      as the anterior maxillary teeth.

PMID- 28434557
TI  - Outcomes of parenchyma-preserving hepatectomy and right hepatectomy for solitary
      small colorectal liver metastasis: A LiverMetSurvey study.
AB  - BACKGROUND: Occasionally, right hepatectomy, rather than parenchyma-preserving
      hepatectomy, has been performed for solitary small colorectal liver metastasis.
      The relative oncologic benefits of parenchyma-preserving hepatectomy and right
      hepatectomy are unclear. This study compared the outcomes of patients with
      solitary small colorectal liver metastasis in the right liver who underwent
      parenchyma-preserving hepatectomy and those who underwent right hepatectomy.
      METHODS: The study population consisted of a multicentric cohort of 21,072
      patients operated for colorectal liver metastasis between 2000 and 2015 whose
      data were collected in the LiverMetSurvey registry. Patients with a
      pathologically confirmed solitary tumor of less than 30 mm in size in the right
      liver were included. The short- and long-term outcomes of patients who underwent
      parenchyma-preserving hepatectomy were compared to those of patients who
      underwent right hepatectomy. RESULTS: Of the 1,720 patients who were eligible for
      the study, 1,478 (86%) underwent parenchyma-preserving hepatectomy and 242 (14%)
      underwent right hepatectomy. The parenchyma-preserving hepatectomy group was
      associated with lower rates of major complications (3% vs 10%; P < .001) and 90
      day mortality (1% vs 3%; P = .008). Liver recurrence occurred similarly in both
      groups (20% vs 22%; P = .39). The 5-year recurrence-free survival and overall
      survival rates were similar in both groups. However, in patients with liver-only
      recurrence, repeat hepatectomy was more frequently performed in the parenchyma
      preserving hepatectomy group than in the right hepatectomy group (67% vs 31%; P <
      .001), and the overall 5-year survival rate was significantly higher in the
      parenchyma-preserving hepatectomy group than in the right hepatectomy group (55%
      vs 23%; P < .001). CONCLUSION: Parenchyma-preserving hepatectomy should be
      considered the standard procedure for solitary small colorectal liver metastasis
      in the right liver when technically feasible.

PMID- 28434559
TI  - What Do George Clooney and Sarah Jessica Parker Have in Common? Big Data.

PMID- 28434558
TI  - Resistance profiles and risk factors of resistant microorganisms in bacteraemia
      of abdominal origin.
AB  - OBJECTIVE: The presence of resistant microorganisms is a major cause of failure
      in initial empirical antimicrobial therapy. The objectives of this study are to
      determine the resistance profile of microorganisms that cause bacteraemia of
      abdominal origin and to identify whether the previous use of antibiotics and the
      place of acquisition of bacteraemia are risk factors associated with the presence
      of resistant organisms. MATERIAL AND METHODS: A clinical, observational,
      epidemiological, retrospective cohort study was conducted with all the adult
      patients admitted to a university hospital from 2011-2013. Antimicrobial
      resistance profiles were described and a 95% confidence interval chi-square test
      was used to determine whether the variables studied were risk factors in the
      isolation of resistant microorganisms. RESULTS: Of the 1245 patients with
      bacteraemia, 212 (17%) presented bacteraemia of abdominal origin. The resistance
      profile highlights the incidence of methicillin resistant Staphylococcus aureus
      (50%), coagulase-negative staphylococci resistant to linezolid (20.58%),
      enterococci resistant to vancomycin (3.12%), Escherichia coli resistant to third
      generation cephalosporins (9.9%) and fluoroquinolones (35.64%), Klebsiella
      pneumoniae resistant to third-generation cephalosporins (8.33%), Pseudomonas
      aeruginosa resistant to fluoroquinolones and carbapenem (25% and 25%
      respectively) and Acinetobacter baumanii resistant to fluoroquinolones and
      carbapenem (100% and 100% respectively), Candida albicans resistant to
      fluconazole (11.11%), single Candida krusei isolate resistant to fluconazole and
      Candida parapsilosis resistant to echinocandins (12.5%). In our study, previous
      use of antibiotics had a statistically significant association with the isolation
      of resistant microorganisms (P=.013) but not the place of acquisition of
      bacteraemia (P=.239). CONCLUSION: Establishing the incidence of resistant
      organisms can improve empirical antimicrobial therapy in patients with
      bacteraemia of abdominal origin. Previous use of antibiotics was statistically
      significantly related to the isolation of resistant microorganisms.

PMID- 28434562
TI  - Advancing the ball or holding the line in concussion?

PMID- 28434560
TI  - Accelerated fatigue testing of dentin-composite bond with continuously increasing
      load.
AB  - OBJECTIVES: The aim of this study was to evaluate an accelerated fatigue test
      method that used a continuously increasing load for testing the dentin-composite
      bond strength. METHODS: Dentin-composite disks (phi5mm*2mm) made from bovine
      incisor roots were subjected to cyclic diametral compression with a continuously
      increasingly load amplitude. Two different load profiles, linear and nonlinear
      with respect to the number of cycles, were considered. The data were then
      analyzed by using a probabilistic failure model based on the Weakest-Link Theory
      and the classical stress-life function, before being transformed to simulate
      clinical data of direct restorations. RESULTS: All the experimental data could be
      well fitted with a 2-parameter Weibull function. However, a calibration was
      required for the effective stress amplitude to account for the difference between
      static and cyclic loading. Good agreement was then obtained between theory and
      experiments for both load profiles. The in vitro model also successfully
      simulated the clinical data. SIGNIFICANCE: The method presented will allow tooth
      composite interfacial fatigue parameters to be determined more efficiently. With
      suitable calibration, the in vitro model can also be used to assess composite
      systems in a more clinically relevant manner.

PMID- 28434561
TI  - Concentration-response of short-term ozone exposure and hospital admissions for
      asthma in Texas.
AB  - BACKGROUND: Short-term exposure to ozone has been associated with asthma hospital
      admissions (HA) and emergency department (ED) visits, but the shape of the
      concentration-response (C-R) curve is unclear. METHODS: We conducted a time
      series analysis of asthma HAs and ambient ozone concentrations in six
      metropolitan areas in Texas from 2001 to 2013. Using generalized linear
      regression models, we estimated the effect of daily 8-hour maximum ozone
      concentrations on asthma HAs for all ages combined, and for those aged 5-14, 15
      64, and 65+years. We fit penalized regression splines to evaluate the shape of
      the C-R curves. RESULTS: Using a log-linear model, estimated risk per 10ppb
      increase in average daily 8-hour maximum ozone concentrations was highest for
      children (relative risk [RR]=1.047, 95% confidence interval [CI]: 1.025-1.069),
      lower for younger adults (RR=1.018, 95% CI: 1.005-1.032), and null for older
      adults (RR=1.002, 95% CI: 0.981-1.023). However, penalized spline models
      demonstrated significant nonlinear C-R relationships for all ages combined,
      children, and younger adults, indicating the existence of thresholds. We did not
      observe an increased risk of asthma HAs until average daily 8-hour maximum ozone
      concentrations exceeded approximately 40ppb. CONCLUSION: Ozone and asthma HAs are
      significantly associated with each other; susceptibility to ozone is age
      dependent, with children at highest risk. C-R relationships between average daily
      8-hour maximum ozone concentrations and asthma HAs are significantly curvilinear
      for all ages combined, children, and younger adults. These nonlinear
      relationships, as well as the lack of relationship between average daily 8-hour
      maximum and peak ozone concentrations, have important implications for assessing
      risks to human health in regulatory settings.

PMID- 28434563
TI  - Pediatric clinical trials-number needed to recruit.

PMID- 28434564
TI  - 50 Years Ago in The Journal of Pediatrics: Feeding Studies in Low-Birth-Weight
      Infants.

PMID- 28434565
TI  - Alcohol and children.

PMID- 28434566
TI  - Race and income affects outcomes in juvenile dermatomyositis.

PMID- 28434568
TI  - Early return to physical activity post-concussion associated with reduced
      persistent symptoms.

PMID- 28434567
TI  - Red reflex screening highly sensitive for anterior segment abnormalities.

PMID- 28434569
TI  - Hormonal therapy with vigabatrin is superior to hormonal therapy alone in
      infantile spasms.

PMID- 28434570
TI  - Novel binocular iPad game treatment for amblyopia.

PMID- 28434571
TI  - Ultrasound skin marking increases lumbar puncture success in infants.

PMID- 28434572
TI  - Pulmonary arterial capacitance index is a strong predictor for adverse outcome in
      children with idiopathic and heritable pulmonary arterial hypertension:
      methodological issues to avoid misinterpretation.

PMID- 28434573
TI  - Correction.

PMID- 28434575
TI  - Who orders echocardigrams?

PMID- 28434574
TI  - 50 Years Ago in The Journal of Pediatrics: Intervertebral Disk Infection in
      Children.

PMID- 28434576
TI  - Can lumbar puncture be deferred in febrile neonates with suspected UTI?

PMID- 28434577
TI  - 50 Years Ago in The Journal of Pediatrics: Thymic Dysplasia ("Swiss
      Agammaglobulinemia"). I. Graft Versus Host Reaction following Bone-Marrow
      Transfusion.

PMID- 28434578
TI  - 50 Years Ago in The Journal of Pediatrics: The Normal Achilles Tendon Reflex Time
      in Children as Measured with the Photomograph.

PMID- 28434579
TI  - Relationship of smoking quantity with outcome measures in patients with
      ankylosing spondylitis: Comments on the article by Villaverde-Garcia V. et al.

PMID- 28434580
TI  - [Gaceta Sanitaria joins the REWARD initiative to improve biomedical research and
      reduce waste in science].

PMID- 28434581
TI  - Hearing loss and auditory plasticity.

PMID- 28434582
TI  - Effectiveness between early and late temporary ileostomy closure in patients with
      rectal cancer: A prospective study.
AB  - A temporary stoma is often used in rectal cancer surgery to protect a distal
      anastomosis, which remains a major concern after rectal cancer surgery,
      particularly after low anterior resection. The temporary stoma is scheduled for
      closure. However, the optimal time of closure of the protecting stoma remains
      unclear because of sparse studies and data. We aimed to detect the efficacy
      between early and late temporary ileostomy closure in patients with rectal cancer
      during or after neoadjuvant chemoradiotherapy. We conducted a prospective, 2
      group design between early and late ileostomy closure group in patients after
      rectal cancer surgery with temporary stoma. Participants were recruited in a
      teaching hospital in Guangzhou, China. A total of 161 patients confirmed
      diagnosis of rectal cancer underwent curative surgery and temporary ileostomy.
      Participants with temporary ileostomy received closure surgery after 1 (early) or
      6 (late) months were assessed by clinical parameters and quality of life.
      Patients in late closure group received more adjuvant chemotherapy cycles but
      with comparable incidence of stoma closure-related complications and length of
      hospital stay compared to early closure group. Participants in late closure group
      with standardized postoperative chemotherapy might have a better prognosis
      compared with those in early closure group. An increased emphasis should be given
      to choose the optimal closure time of patients with rectal cancer having
      temporary ileostomy. Colorectal nurses could provide support to physician for
      observation of prognosis of different closure time.

PMID- 28434583
TI  - A proposal for new neurorehabilitative intervention on Moebius Syndrome patients
      after 'smile surgery'. Proof of concept based on mirror neuron system properties
      and hand-mouth synergistic activity.
AB  - Studies of the last twenty years on the motor and premotor cortices of primates
      demonstrated that the motor system is involved in the control and initiation of
      movements, and in higher cognitive processes, such as action understanding,
      imitation, and empathy. Mirror neurons are only one example of such theoretical
      shift. Their properties demonstrate that motor and sensory processing are coupled
      in the brain. Such knowledge has been also central for designing new
      neurorehabilitative therapies for patients suffering from brain injuries and
      consequent motor deficits. Moebius Syndrome patients, for example, are incapable
      of moving their facial muscles, which are fundamental for affective
      communication. These patients face an important challenge after having undergone
      a corrective surgery: reanimating the transplanted muscles to achieve a
      voluntarily control of smiling. We propose two new complementary rehabilitative
      approaches on MBS patients based on observation/imitation therapy (Facial
      Imitation Therapy, FIT) and on hand-mouth motor synergies (Synergistic Activity
      Therapy, SAT). Preliminary results show that our intervention protocol is a
      promising approach for neurorehabilitation of patients with facial palsy.

PMID- 28434584
TI  - How does sex matter? Behavior, stress and animal models of neurobehavioral
      disorders.
AB  - Many aspects of brain functioning exhibit important sex differences that affect
      behavior, mental health and mental disorders. However, most translational
      neuroscience research related to animal models of neurobehavioral disorders are
      carried out in male animals only. Based on published data from our laboratory on
      the House mouse, we discuss the following issues: (1) sex differences in social
      behavior of wild-derived mice; (2) artificial selection of laboratory strains and
      its consequences on social and reproductive competition; (3) sex-dependent
      effects of common experimental procedures; (4) differential effects of
      developmental events: the case of endocrine disruption; (5) implications for
      female models of stress and neurobehavioral disorders. Altogether, this review of
      data outline the marked differences of male and female responses to different
      social challenges and evinces the current lack of a relevant female mouse model
      of social stress. Whilst animal modelling is an important approach towards
      understanding mechanisms of neurobehavioral disorders, it is evident that data
      obtained in males may be irrelevant for inferring psychopathology and efficacy of
      pharmacological treatments for females.

PMID- 28434585
TI  - Translating dynamic defense patterns from rodents to people.
AB  - Specific defensive behaviors of rodents are shaped by features of the eliciting
      threat stimuli and situation. Threat scenarios confirmed these relationships in
      people, with results substantially replicated in 4 additional scenario studies.
      Subsequent human studies involve computer games measuring fear as flight from
      threat stimuli and anxiety as alternation between two threats. Stabilometric
      studies have shown reduction in sway (freezing) to inescapable (e.g. with gun
      pointed at subject) threatening photographs; but enhanced lateral sway (flight
      attempts) to escapable threats; (gun pointed away from subject). Relationships
      between threat ambiguity, risk assessment, and anxiety have been validated by
      identification of videos of facial expressions to ambiguous threats, as anxiety;
      and systematic biases toward threat stimuli by anxious individuals. Enhanced
      rumination, interpretable as unsuccessful risk assessment, is a dynamic component
      of both anxiety and depression, particularly in women. While there is less
      experimental work on defensive threat/attack, a transdiagnostic "Fear of Harm"
      phenotype of aggression associated with fear suggests that this is a component of
      pathological as well as normal human defensive behavior.

PMID- 28434586
TI  - The periaqueductal gray and primal emotional processing critical to influence
      complex defensive responses, fear learning and reward seeking.
AB  - The periaqueductal gray (PAG) has been commonly recognized as a downstream site
      in neural networks for the expression of a variety of behaviors and is thought to
      provide stereotyped responses. However, a growing body of evidence suggests that
      the PAG may exert more complex modulation of a number of behavioral responses and
      work as a unique hub supplying primal emotional tone to influence prosencephalic
      sites mediating complex aversive and appetitive responses. Of particular
      relevance, we review how the PAG is involved in influencing complex forms of
      defensive responses, such as circa-strike and risk assessment responses in
      animals. In addition, we discuss putative dorsal PAG ascending paths that are
      likely to convey information related to threatening events to cortico-hippocampal
      amygdalar circuits involved in the processing of fear learning. Finally, we
      discuss the evidence supporting the role of the PAG in reward seeking and note
      that the lateral PAG is part of the circuitry related to goal-oriented responses
      mediating the motivation to hunt and perhaps drug seeking behavior.

PMID- 28434587
TI  - Aligning physiology with psychology: Translational neuroscience in
      neuropsychiatric drug discovery.
AB  - This review presents an overview of some of the pre-clinical and clinical issues
      that have contributed to the failures of potential novel neuropsychiatric drugs,
      which have prompted a re-examination of the role of animal models of
      neuropsychiatric disorders. Advances both in basic neuroscience and technology
      have driven the development of animal models of aspects of neuropsychiatric
      disorders. Genetics and environmental factors have been the primary contributors
      to the development of new animal models. Neuroimaging has contributed to the
      search for biomarkers by which neuropsychiatric disorders may be identified and
      differentiated, its progression monitored and that the effects of therapy
      assessed. Parallel to these theoretical and practical advancements have been the
      changes in the diagnosis and classification of neuropsychiatric disorders from
      DSM-4 to DSM-5, and emergence of the NIH initiatives such as MATRICS; CNTRICS and
      RDoC. These latter changes are shifting our concepts of neuropsychiatric
      disorders away from phenomenology to their biology and thus aligning physiology
      with psychology.

PMID- 28434589
TI  - From an animal model to human patients: An example of a translational study on
      obsessive compulsive disorder (OCD).
AB  - The application of similar analyses enables a direct projection from
      translational research in animals to human studies. Following is an example of
      how the methodology of a specific animal model of obsessive-compulsive disorder
      (OCD) was applied to study human patients. Specifically, the quinpirole rat model
      for OCD was based on analyzing the trajectories of travel among different
      locales, and scoring the set of acts performed at each locale. Applying this
      analytic approach in human patients unveiled various aspects of OCD, such as the
      repetition and addition of acts, incompleteness, and the link between behavior
      and specific locations. It is also illustrated how the same analytical approach
      could be applicable to studying other mental disorders. Finally, it is suggested
      that the development of OCD could be explained by the four-phase sequence of
      Repetition, Addition, Condensation, and Elimination, as outlined in the study of
      ontogeny and phylogeny and applied to normal development of behavior. In OCD,
      this sequence is curtailed, resulting in the abundant repetition and addition of
      acts.

PMID- 28434590
TI  - Studies into abnormal aggression in humans and rodents: Methodological and
      translational aspects.
AB  - Here we review the principles based on which aggression is rendered abnormal in
      humans and laboratory rodents, and comparatively overview the main methodological
      approaches based on which this behavior is studied in the two categories of
      subjects. It appears that the discriminating property of abnormal aggression is
      rule breaking, which renders aggression dysfunctional from the point of view of
      the perpetrator. We show that rodent models of abnormal aggression were created
      by the translation of human conditions into rodent equivalents, and discuss how
      findings obtained with such models may be "translated back" to human conditions
      when the mechanisms underlying aggression and its possibilities of treatment are
      investigated. We suggest that the complementary nature of human and rodent
      research approaches invite a more intense cross-talk between the two sides of
      aggression research than the one presently observed.

PMID- 28434588
TI  - The endocannabinoid system as a target for novel anxiolytic drugs.
AB  - The endocannabinoid (eCB) system has attracted attention for its role in various
      behavioral and brain functions, and as a therapeutic target in neuropsychiatric
      disease states, including anxiety disorders and other conditions resulting from
      dysfunctional responses to stress. In this mini-review, we highlight components
      of the eCB system that offer potential 'druggable' targets for new anxiolytic
      medications, emphasizing some of the less well-discussed options. We discuss how
      selectively amplifying eCBs recruitment by interfering with eCB-degradation, via
      fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), has been
      linked to reductions in anxiety-like behaviors in rodents and variation in human
      anxiety symptoms. We also discuss a non-canonical route to regulate eCB
      degradation that involves interfering with cyclooxygenase-2 (COX-2). Next, we
      discuss approaches to targeting eCB receptor-signaling in ways that do not
      involve the cannabinoid receptor subtype 1 (CB1R); by targeting the CB2R subtype
      and the transient receptor potential vanilloid type 1 (TRPV1). Finally, we review
      evidence that cannabidiol (CBD), while representing a less specific
      pharmacological approach, may be another way to modulate eCBs and interacting
      neurotransmitter systems to alleviate anxiety. Taken together, these various
      approaches provide a range of plausible paths to developing novel compounds that
      could prove useful for treating trauma-related and anxiety disorders.

PMID- 28434592
TI  - Fenestrated and branched endovascular aortic repair has reached a state of
      maturity.

PMID- 28434594
TI  - Invited commentary.

PMID- 28434593
TI  - Invited commentary.

PMID- 28434595
TI  - Aneurysmosis requiring extensive longitudinal care.

PMID- 28434596
TI  - Choices.

PMID- 28434591
TI  - Oxytocin and vasopressin neural networks: Implications for social behavioral
      diversity and translational neuroscience.
AB  - Oxytocin- and vasopressin-related systems are present in invertebrate and
      vertebrate bilaterian animals, including humans, and exhibit conserved
      neuroanatomical and functional properties. In vertebrates, these systems
      innervate conserved neural networks that regulate social learning and behavior,
      including conspecific recognition, social attachment, and parental behavior.
      Individual and species-level variation in central organization of oxytocin and
      vasopressin systems has been linked to individual and species variation in social
      learning and behavior. In humans, genetic polymorphisms in the genes encoding
      oxytocin and vasopressin peptides and/or their respective target receptors have
      been associated with individual variation in social recognition, social
      attachment phenotypes, parental behavior, and psychiatric phenotypes such as
      autism. Here we describe both conserved and variable features of central oxytocin
      and vasopressin systems in the context of social behavioral diversity, with a
      particular focus on neural networks that modulate social learning, behavior, and
      salience of sociosensory stimuli during species-typical social contexts.

PMID- 28434597
TI  - The vascular surgeon's roadmap to success in the Quality Payment Program.

PMID- 28434598
TI  - Abdominal aortic aneurysm screening.

PMID- 28434599
TI  - Reply.

PMID- 28434600
TI  - Regarding "A short time interval between the neurologic index event and carotid
      endarterectomy is not a risk factor for carotid surgery".

PMID- 28434601
TI  - Regarding "Description of a risk predictive model of 30-day postoperative
      mortality after elective abdominal aortic aneurysm repair".

PMID- 28434602
TI  - Reply.

PMID- 28434603
TI  - Regarding "Outcomes for symptomatic abdominal aortic aneurysms in the American
      College of Surgeons National Surgical Quality Improvement Program".

PMID- 28434604
TI  - Regarding "Perioperative and long-term impact of chronic kidney disease on
      carotid artery interventions".

PMID- 28434605
TI  - Reply.

PMID- 28434606
TI  - Reply.

PMID- 28434607
TI  - A Review of the Design and Management of Footbaths for Dairy Cattle.
AB  - This article summarizes current footbath practices, questions the mechanism by
      which footbaths function, and reviews the available scientific literature testing
      footbaths in the field. Copper sulfate appears the most efficacious agent to
      include in a footbath program, but disposal concerns should limit the frequency
      of its use. Other agents such as formaldehyde have some merit when used with
      care. Use of water alone in a flush bath appears to have minimal impact.
      Footbaths should be used as infrequently as possible to achieve lameness
      prevention goals for the herd.

PMID- 28434608
TI  - A concept analysis of moral resilience.
AB  - BACKGROUND: Nurses experience moral distress, which has led to emotional
      distress, frustration, anger, and nurse attrition. Overcoming moral distress has
      become a significant focus in nursing research. PURPOSE: The continued focus on
      moral distress has not produced sustainable solutions within the nursing
      profession. Since positive language may alter the outcomes of morally distressing
      situations, we look to better understand one such positive phrase, moral
      resilience. METHODS: We explored moral resilience through a literature search
      using 11 databases to identify instances of the phrase. Occurrences of moral
      resilience were then divided into three distinct categories: antecedents,
      attributes, and consequences, and following this, major themes within each
      category were identified. DISCUSSION: There is a dearth of scholarship on moral
      resilience, and additionally, there is currently no unifying definition. Despite
      this, our analysis offers promising direction in refining the concept.
      CONCLUSION: This concept analysis reveals differences in how moral resilience is
      understood. More conceptual work is needed to refine the definition of moral
      resilience and understand how the concept is useful in mitigating the negative
      consequences of moral distress and other types of moral adversity.

PMID- 28434609
TI  - Letter to the editor in response to the Dols et al. article in the
      January/February, 2017 issue of No.

PMID- 28434610
TI  - Gene Duplicates: Agents of Robustness or Fragility?
AB  - A recent analysis of paralog deletion in yeast has shown that functional
      compensation and dependency occur equally. While theory predicts that
      compensation produces robustness, the authors hypothesized that stabilization of
      one paralogous protein through interaction with its copy could explain
      dependency. Here, we provide alternative explanations, such as selection for
      increased protein dosage and hypofunctionalization.

PMID- 28434611
TI  - Alcohol intake and risk of rosacea in US women.
AB  - BACKGROUND: The epidemiologic association between alcohol and rosacea is unclear
      and inconsistent based on the previous cross-sectional or case-control studies.
      OBJECTIVE: We conducted a cohort study to determine the association between
      alcohol intake and the risk of rosacea in women. METHODS: A total of 82,737 women
      were included from the Nurses' Health Study II (1991-2005). Information on
      alcohol intake was collected every 4 years during follow-up. Information on
      history of clinician-diagnosed rosacea and year of diagnosis was collected in
      2005. RESULTS: Over 14 years of follow-up, we identified 4945 cases of rosacea.
      Compared with never drinkers, increased alcohol intake was associated with a
      significantly increased risk of rosacea (Ptrend <.0001). The multivariate
      adjusted hazard ratios (HRs) and confidence intervals (CIs) were 1.12 (95% CI
      1.05-1.20) for alcohol intake of 1-4 g/day and 1.53 (1.26-1.84) for >=30 g/day.
      The associations remained consistent across categories of smoking status. Further
      examination of types of alcoholic beverage consumed revealed that white wine
      (Ptrend <.0001) and liquor intake (Ptrend = .0006) were significantly associated
      with a higher risk of rosacea. LIMITATIONS: This was an epidemiologic study
      without examination into etiologic mechanisms. CONCLUSIONS: Alcohol intake was
      significantly associated with an increased risk of rosacea in women.

PMID- 28434613
TI  - The diversity of beef safety: A global reason to strengthen our current systems.
AB  - The purpose of this paper is to propose a more integrated and more aggressive
      system approach to food safety rather than focusing on one segment of the
      industry, or on one approach as described by or constrained by one set of
      regulations. We focus on the prevalence and control measures for Salmonella and
      pathogenic Escherichia coli, particularly, Shiga toxin-producing E. coli (STEC)
      in live cattle on the farm and in the final raw beef product at retail. We
      describe the antimicrobial and process control strategies most commonly used
      during slaughter and processing to prevent and reduce the frequency and
      concentration of these pathogens in the final product, and we propose points
      along the food chain where more interventions can be applied to ultimately reduce
      the prevalence of foodborne pathogens associated with beef and beef products, and
      to protect public health as well the global food supply.

PMID- 28434612
TI  - Tracking nitrate sources in groundwater and associated health risk for rural
      communities in the White Volta River basin of Ghana using isotopic approach
      (delta15N, delta18ONO3 and 3H).
AB  - In this study, we present a first attempt on the use of integrated hydro-chemical
      and isotopic technique to trace the sources of groundwater nitrate contamination
      in the Upper East Region of Ghana to aid the sustainable management of this vital
      resource. The objectives of the study are (1) assess the present status and
      spatial distribution of the nitrate contamination (2) identify and distinguish
      the most likely sources of nitrate , (3) identify the relationship between 3H and
      NO3- and F-, and (4) ascertain the potential human risk from exposure to nitrate
      contamination. The results showed that, nitrate concentrations varied from 0.42
      to 431.17, 0.83 to 143.94, 0.03 to 28.94mg/l with mean values of 36.09, 21.54 and
      5.01mg/l for boreholes, hand dug wells and the surface water respectively. These
      values showed that, about 95% of boreholes and hand dug wells and 45% of the
      surface water have nitrate concentration above the baseline value in the area.
      The NO3-/Cl- ratio showed that, 98.4%, 95% and 64% of the NO3- in the borehole,
      hand dug wells and the surface water are from anthropogenic activities. The
      delta15NNO3 and delta18ONO3- data confirmed that NO3- in the samples was
      predominantly derived from manure (human and animal waste) and denitrification
      occurring in some areas. The isotopic data further affirms the hydro-chemical
      interpretation that, chemical fertilizer and atmospheric deposition are unlikely
      sources of NO3- in the area. The relationship between 3H and NO3- concentrations
      showed that, higher NO3- values are associated with younger waters. Non
      carcinogenic health risk for adults and children posed by oral ingestion of the
      NO3- contaminated water revealed some degree of health risk, especially to
      children whose risk is about 72% higher. The study provides a conceptual model of
      the NO3- dynamics and some recommendation for groundwater management in the area.

PMID- 28434614
TI  - Rebalancing Altered Computations: Considering the Role of Neural Excitation and
      Inhibition Balance Across the Psychiatric Spectrum.

PMID- 28434618
TI  - Borderline left ventricle: Trying to see the forest for the trees.

PMID- 28434615
TI  - Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing
      Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders.
AB  - Recent theoretical accounts have proposed excitation and inhibition (E/I)
      imbalance as a possible mechanistic, network-level hypothesis underlying neural
      and behavioral dysfunction across neurodevelopmental disorders, particularly
      autism spectrum disorder (ASD) and schizophrenia (SCZ). These two disorders share
      some overlap in their clinical presentation as well as convergence in their
      underlying genes and neurobiology. However, there are also clear points of
      dissociation in terms of phenotypes and putatively affected neural circuitry. We
      highlight emerging work from the clinical neuroscience literature examining
      neural correlates of E/I imbalance across children and adults with ASD and adults
      with both chronic and early-course SCZ. We discuss findings from diverse
      neuroimaging studies across distinct modalities, conducted with
      electroencephalography, magnetoencephalography, proton magnetic resonance
      spectroscopy, and functional magnetic resonance imaging, including effects
      observed both during task and at rest. Throughout this review, we discuss points
      of convergence and divergence in the ASD and SCZ literature, with a focus on
      disruptions in neural E/I balance. We also consider these findings in relation to
      predictions generated by theoretical neuroscience, particularly computational
      models predicting E/I imbalance across disorders. Finally, we discuss how human
      noninvasive neuroimaging can benefit from pharmacological challenge studies to
      reveal mechanisms in ASD and SCZ. Collectively, we attempt to shed light on
      shared and divergent neuroimaging effects across disorders with the goal of
      informing future research examining the mechanisms underlying the E/I imbalance
      hypothesis across neurodevelopmental disorders. We posit that such translational
      efforts are vital to facilitate development of neurobiologically informed
      treatment strategies across neuropsychiatric conditions.

PMID- 28434619
TI  - It's been a long time coming, but it finally came.

PMID- 28434617
TI  - Stem Cell Lineage Infidelity Drives Wound Repair and Cancer.
AB  - Tissue stem cells contribute to tissue regeneration and wound repair through
      cellular programs that can be hijacked by cancer cells. Here, we investigate such
      a phenomenon in skin, where during homeostasis, stem cells of the epidermis and
      hair follicle fuel their respective tissues. We find that breakdown of stem cell
      lineage confinement-granting privileges associated with both fates-is not only
      hallmark but also functional in cancer development. We show that lineage
      plasticity is critical in wound repair, where it operates transiently to redirect
      fates. Investigating mechanism, we discover that irrespective of cellular origin,
      lineage infidelity occurs in wounding when stress-responsive enhancers become
      activated and override homeostatic enhancers that govern lineage specificity. In
      cancer, stress-responsive transcription factor levels rise, causing lineage
      commanders to reach excess. When lineage and stress factors collaborate, they
      activate oncogenic enhancers that distinguish cancers from wounds.

PMID- 28434620
TI  - Fontan survival: As good as it gets?

PMID- 28434616
TI  - Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A
      Translational and Computational Neuroscience Perspective.
AB  - The functional optimization of neural ensembles is central to human higher
      cognitive functions. When the functions through which neural activity is tuned
      fail to develop or break down, symptoms and cognitive impairments arise. This
      review considers ways in which disturbances in the balance of excitation and
      inhibition might develop and be expressed in cortical networks in association
      with schizophrenia. This presentation is framed within a developmental
      perspective that begins with disturbances in glutamate synaptic development in
      utero. It considers developmental correlates and consequences, including
      compensatory mechanisms that increase intrinsic excitability or reduce inhibitory
      tone. It also considers the possibility that these homeostatic increases in
      excitability have potential negative functional and structural consequences.
      These negative functional consequences of disinhibition may include reduced
      working memory-related cortical activity associated with the downslope of the
      "inverted-U" input-output curve, impaired spatial tuning of neural activity and
      impaired sparse coding of information, and deficits in the temporal tuning of
      neural activity and its implication for neural codes. The review concludes by
      considering the functional significance of noisy activity for neural network
      function. The presentation draws on computational neuroscience and pharmacologic
      and genetic studies in animals and humans, particularly those involving N-methyl
      D-aspartate glutamate receptor antagonists, to illustrate principles of network
      regulation that give rise to features of neural dysfunction associated with
      schizophrenia. While this presentation focuses on schizophrenia, the general
      principles outlined in the review may have broad implications for considering
      disturbances in the regulation of neural ensembles in psychiatric disorders.

PMID- 28434621
TI  - Mesenchymal stem cells for cardiac repair: Is the placenta the answer?

PMID- 28434622
TI  - Young and thriving is okay; young and not thriving is not.

PMID- 28434623
TI  - Does unilateral insular resection disturb personality? A study with epileptic
      patients.
AB  - The insula is now regarded as a potential site of epileptogenesis in drug
      resistant epilepsy, and the advent of microsurgical techniques has allowed
      insular cortectomy to become a treatment of choice when the insular cortex is
      involved in the seizure focus. However, considering the evidence of an insular
      role in socio-emotional processing, it remains unknown whether these cortical
      resections disturb personality and social behavior as experienced in daily life.
      We examined such changes in a group of patients (n=19) who underwent epilepsy
      surgery involving partial or complete resection of the insula, and compared them
      to a group of patients who underwent standard temporal lobe epilepsy (TLE)
      surgery (n=19) as a lesion-control group. Participants were assessed on the Iowa
      Scales of Personality Change, filled by a close relative at least six months
      after surgery. While postoperative changes did not significantly differ between
      groups on any of the ISPC items, insular resections were associated with mild but
      significant increases in irritability, emotional lability, anxiety, and frugality
      postoperatively, which, apart from anxiety, were not significant among TLE
      patients. Our results are congruent with the idea that the insula contributes to
      emotion processing. To our knowledge, this study is the first to systematically
      assess personality changes in a consecutive sample of patients with insular
      resections.

PMID- 28434624
TI  - Obesity and kidney disease: Hidden consequences of the epidemic.

PMID- 28434625
TI  - Prinzmetals angina presenting with non critical lesion with normal FFR -to stent
      or not to stent.
AB  - Variant angina also called Prinzmetals angina is an enigma characterized by
      transient circadian symptoms of chest pain associated with ECG changes. The
      patient is symptom free with normal ECG and echo during symptom free periods. We
      present a case associated with transient ST-segment elevation with non critical
      lesion with normal FFR.

PMID- 28434626
TI  - [Continuous positive airway pressure in obstructive sleep apnea].
AB  - Continuous positive airway pressure (CPAP) is currently the most used and
      efficient therapy in OSAS. Efficiency of CPAP on sleep respiratory disorders is
      the same whether in fixed or automatic mode. Larger studies are required to
      evaluate their respective beneficial impact on cardiovascular or metabolic
      complications of OSAS. Close medical monitoring is necessary during the first
      weeks of CPAP therapy. Compliance to CPAP therapy is crucial for efficacy in
      preventing cardiovascular or metabolic complications of OSAS. As beneficial
      effects of CPAP in obese patients are modest, on blood pressure levels and
      metabolic disorders, its use has to be part of a comprehensive care of OSAS and
      related comorbidities.

PMID- 28434627
TI  - [Sports in children with congenital heart diseases].
AB  - The practice of physical activity is one of the essential elements for health in
      general but also for the well-being and the quality of life. It is highly
      desirable to encourage physical activities in children with congenital heart
      diseases, taking into account all the benefits associated with this practice
      (quality of life, life expectancy) and this especially since these children often
      have limited capacity (due to their heart disease but also often by relative
      deconditioning). While there is a transient increase in risk of cardiac
      complications during intense activity, it would nevertheless be inappropriate to
      contra-indicate physical activities considering the well-known benefits in the
      medium and long term. The risks associated with the practice of physical activity
      must be assessed, on one hand, in terms of the severity of the heart disease, and
      on the other hand, on the nature and intensity of the activity. The stress test
      is here an essential tool because it helps to assess the physical capacity and
      cardiorespiratory adaptations to exercise. The international recommendations for
      competitive sports generally give an appropriate advice for a specific situation
      but the practice of moderate activity or leisure sports which are highly
      desirable should not be neglected and be strongly encouraged.

PMID- 28434628
TI  - Becoming patient-centred: sobering insight into CPE-positive patients'
      experiences of clinical care.

PMID- 28434629
TI  - Does appropriate empiric antibiotic therapy modify intensive care unit-acquired
      Enterobacteriaceae bacteraemia mortality and discharge?
AB  - BACKGROUND: Conflicting results have been found regarding outcomes of intensive
      care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially
      modifying effect of appropriate empiric antibiotic therapy. AIM: To evaluate
      these associations while adjusting for potential time-varying confounding using
      methods from the causal inference literature. METHODS: Patients who stayed more
      than two days in two general ICUs in England between 2002 and 2006 were included
      in this cohort study. Marginal structural models with inverse probability
      weighting were used to estimate the mortality and discharge associated with
      Enterobacteriaceae bacteraemia and the impact of appropriate empiric antibiotic
      therapy on these outcomes. FINDINGS: Among 3411 ICU admissions, 195 (5.7%) ICU
      acquired Enterobacteriaceae bacteraemia cases occurred. Enterobacteriaceae
      bacteraemia was associated with an increased daily risk of ICU death [cause
      specific hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.10-1.99] and a
      reduced daily risk of ICU discharge (HR: 0.66; 95% CI: 0.54-0.80). Appropriate
      empiric antibiotic therapy did not significantly modify ICU mortality (HR: 1.08;
      95% CI: 0.59-1.97) or discharge (HR: 0.91; 95% CI: 0.63-1.32). CONCLUSION: ICU
      acquired Enterobacteriaceae bacteraemia was associated with an increased daily
      risk of ICU mortality. Furthermore, the daily discharge rate was also lower after
      acquiring infection, even when adjusting for time-varying confounding using
      appropriate methodology. No evidence was found for a beneficial modifying effect
      of appropriate empiric antibiotic therapy on ICU mortality and discharge.

PMID- 28434630
TI  - Generalized characteristic ratios assignment for commensurate fractional order
      systems with one zero.
AB  - In this paper, a new method for determination of the desired characteristic
      equation and zero location of commensurate fractional order systems is presented.
      The concept of the characteristic ratio is extended for zero-including
      commensurate fractional order systems. The generalized version of characteristic
      ratios is defined such that the time-scaling property of characteristic ratios is
      also preserved. The monotonicity of the magnitude frequency response is employed
      to assign the generalized characteristic ratios for commensurate fractional order
      transfer functions with one zero. A simple pattern for characteristic ratios is
      proposed to reach a non-overshooting step response. Then, the proposed pattern is
      revisited to reach a low overshoot (say for example 2%) step response. Finally,
      zero-including controllers such as fractional order PI or lag (lead) controllers
      are designed using generalized characteristic ratios assignment method. Numerical
      simulations are provided to show the efficiency of the so designed controllers.

PMID- 28434631
TI  - Passivity analysis of neural networks with two different Markovian jumping
      parameters and mixed time delays.
AB  - This paper studies the problem of passivity analysis for neural networks with two
      different Markovian jumping parameters and mixed time delays utilizing some
      integral inequalities. The integral inequalities produce sharper bounds than what
      the Jensen's inequality produces, consequently, better results are obtained. The
      Markovian jumping parameters in connection weight matrices and discrete delay are
      assumed to be different in the system model. By constructing a new appropriate
      Lyapunov-Krasovskii functional (LKF), some sufficient conditions are established
      which guarantee the passivity of the proposed model. Numerical examples are given
      to show the less conservatism and effectiveness of the proposed method.

PMID- 28434632
TI  - Obesity and lower urinary tract dysfunction in children and adolescents: Further
      research into new relationships.
AB  - INTRODUCTION: Lower urinary tract dysfunction (LUTD) involves faults in the
      filling and emptying phases of bladder function in toilet-trained children with
      no previous infection or any other obvious pathology. Lower urinary tract
      dysfunction is associated with conditions such as vesicoureteral reflux,
      recurrent urinary infection, behavioral alterations and decreased quality of
      life. The literature suggests an association between LUTD and obesity; however,
      the association between each individual symptom and obesity has yet to be
      evaluated. OBJECTIVE: To evaluate the association between excess weight and LUTD
      in children and adolescents in a community-based sample. STUDY DESIGN: This cross
      sectional study included 423 children and adolescents aged 5-17 years, and
      randomly selected in public places and schools between May and July 2015. The
      participants and their mothers completed the Dysfunctional Voiding Scoring System
      (DVSS) questionnaire, except for the questions on constipation and with the
      addition of a question on enuresis. They also completed the Rome III
      questionnaire, in which two positive responses defined the presence of
      constipation. Participants were classified as being of normal weight, overweight
      or obese, which was based on the BMI-for-age indicator. RESULTS: Mean age was 9.7
      years (SD 2.9), with girls comprising 50.6% of the sample and adolescents 52.5%.
      The prevalence of LUTD was 7.1%, with 13.5% of participants being overweight and
      12.1% obese (Figure). Constipation was present in 5.9% of participants and
      enuresis in 10.8%. In the multivariate analysis, three factors were independently
      and significantly associated with a positive DVSS: age <10 years (beta = 0.76;
      95% CI: 0.34-1.18), constipation (beta = 1.79; 95% CI: 0.88-2.70) and obesity
      (beta = 0.89; 95% CI: 0.25-1.52). DISCUSSION: Only bladder filling symptoms were
      associated with obesity. This may be explained by the fact that both obese
      individuals and those with emptying symptoms were shown to have activation
      alterations in the same brain regions. One limitation of this study was the use
      of questionnaires alone to diagnose LUTD and constipation. CONCLUSION: Only the
      bladder-emptying symptoms of LUTD appear to be associated with obesity. This
      hypothesis may serve as a basis for future studies.

PMID- 28434633
TI  - Echocardiographic evaluation of left ventricular mass index in children with
      hypospadias after hormonal stimulation with topical testosterone: A randomized
      controlled trial.
AB  - INTRODUCTION: Testosterone is often used in the preoperative period of
      hypospadias surgery. Previous studies have demonstrated the presence of androgen
      receptors in cardiac myocytes that can modulate the phenotype. The use of
      supraphysiological doses of androgens can lead to toxicity on the heart muscle
      and, in some cases, to left ventricular hypertrophy. This randomized double blind
      controlled clinical trial aims to evaluate the effect of topical testosterone on
      left ventricular mass index in boys with hypospadias. MATERIALS AND METHODS: Boys
      with hypospadias aged 6 months to 9 years were included. Children were divided
      into two groups: G1 - boys who received testosterone propionate 1% ointment twice
      a day for 30 days, and G2 - boys receiving placebo ointment in the same regimen.
      All children were submitted to bi-dimensional echocardiographic evaluation to
      compare the left ventricular mass index, blood pressure, and body mass index
      before and after treatment (30 and 90 days). Levels of serum testosterone, LH,
      and FSH were measured. RESULTS: Thirty-five children were analyzed: 17 in G1 and
      18 in G2. No differences were found in left ventricular mass index (left
      ventricular mass indexed by body surface area) prior to treatment. Left
      ventricular mass index was 59.21 +/- 11.91 g/m2 in G1 and 55.12 +/- 8.29 g/m2 in
      G2 (p = 0.244) after 30 days of treatment, and 61.13 +/- 11.69 g/m2 in G1 and
      62.84 +/- 35.99 g/m2 in G2 (p = 0.852) after 90 days. Serum testosterone levels
      were 12 (7-80) ng/dL in G1 and 5 (5-7) ng/dL in G2 (p = 0.018) after 30 days of
      treatment, and 10 (5-11) ng/dL in G1 and 5 (4-5) ng/dL in G2 (p = 0.155), after
      90 days (Figure). There was a small increase in systolic blood pressure (SBP)
      after 30 days (83.82 +/- 7.18 mmHg) in the group who receive testosterone (G1)
      compared with controls (77.5 +/- 6.69 mmHg) (p = 0.010). After 90 days, SBP
      levels returned to basal levels in G1 (82.35 +/- 5.62 mmHg) and in G2 (81.38 +/-
      4.79 mmHg) (p = 0.588). CONCLUSION: Topical testosterone can be considered safe
      in the preoperative period of children with hypospadias with no risk of left
      ventricular hypertrophy. An increase in systolic blood pressure occurs while
      using testosterone but it is transitory, returning to normal levels after 90
      days.

PMID- 28434634
TI  - Hypospadias surgery in England: Higher volume centres have lower complication
      rates.
AB  - INTRODUCTION: Hypospadias surgery has progressed steadily over recent years.
      There remains considerable variation in the operative management of boys with
      hypospadias in the UK, and it is therefore difficult to identify acceptable
      standards with regards to reoperation rates. OBJECTIVE: To determine the
      frequency of reoperations and complications from all centres performing
      hypospadias surgery in England and to identify variables that influence outcome.
      METHODS: All children undergoing NHS hypospadias surgery in England between 1999
      and 2009 were identified using the Hospital Episode Statistics database. Patient
      demographics, centre type, and associated diagnostic (ICD-10) and treatment codes
      (OPCS4.6) were collected for both primary repairs and postoperative
      complications. Centres were classed as high volume if they performed an average
      of 20 or more operations a year. Operative complications were split into
      revisions (repeat repairs), repairs of urethral fistulae, repairs of meatal
      stenosis, or urethral stricture repairs. Statistical analysis included logistic
      regression, Spearman's correlation, and Mann-Whitney U for non-parametric data,
      with p < 0.05 taken as significant. Data are presented as median (interquartile
      range) unless otherwise stated. RESULTS: children underwent a total of 23,962
      operations at 75 centres in England during the study period. The median age at
      primary repair was 21 (15-38) months. The overall complication rate was 18.1%.
      The median complication rate for individual centres was 20.0% (13.9-27.4%)
      overall; 10.8% (4.7-15.9%) for revision procedures, 8.1% (5.5-11.7%) for urethral
      fistulae, 2.3% (1.1-3.7%) for meatal stenosis repairs, and 1.8% (0-2.8%) for
      urethral strictures. High volume centres had significantly lower complication
      rates than low volume centres (17.5% vs. 25%, p = 0.01) (Figure), and this was
      proven to be an independent predictor of outcomes (p = 0.01). Staged repairs were
      associated with more complications (p < 0.001); however, patient age and centre
      type were not. Median time to repair of complication was 13 (8-22) months.
      DISCUSSION: This national population-based study used hospital episode statistics
      data. While accuracy is high and it has been validated for use in research, it
      has intrinsic limitations which affect our study. We are unable to fully account
      for the severity of hypospadias or the number of operating surgeons within
      institutions. CONCLUSIONS: This study has found a clear relationship between
      caseload volume and complications following hypospadias surgery. Furthermore,
      there is significant variability between centres in terms of their surgical
      outcomes. Taken together these results suggest that surgeons, particularly those
      in centres with small caseloads should assess their results against such
      benchmarks when evaluating the service they provide.

PMID- 28434635
TI  - Readmissions, unplanned emergency room visits, and surgical retreatment rates
      after anti-reflux procedures.
AB  - INTRODUCTION/BACKGROUND: The choice between endoscopic injection (EI) and
      ureteroneocystotomy (UNC) for surgical correction of vesicoureteral reflux (VUR)
      is controversial. OBJECTIVE: To compare postoperative outcomes of EI vs UNC.
      STUDY DESIGN: This study reviewed linked inpatient (SID), ambulatory surgery
      (SASD), and emergency department (SEDD) data from five states in the United
      States (2007-10) to identify pediatric patients with primary VUR undergoing EI or
      UNC as an initial surgical intervention. Unplanned readmissions, additional
      procedures, and emergency room (ER) visits were extracted. Statistical analysis
      was performed using multivariate logistic regression using generalized estimating
      equation (GEE) to adjust for hospital-level clustering. RESULTS: The study
      identified 2556 UNC and 1997 EI procedures. Compared with patients undergoing EI,
      those who underwent UNC were more likely to be younger (4.6 vs 6.0 years, P <
      0.001), male (30 vs 20%, P < 0.001), and publicly insured (34 vs 29%, P < 0.001).
      As shown in Summary Figure, compared with EI, UNC patients had lower rates of
      additional anti-reflux procedures within 12 months (25 (1.0) vs 121 (6.1%), P <
      0.001), but a higher rate of 30-day and 90-day readmissions and ER visits. On
      multivariate analysis, patients treated by UNC remained at higher odds of being
      readmitted (OR = 4.45; 2.69 in 30 days; 90 days, P < 0.001) and to have
      postoperative ER visits (OR = 3.33; 2.26 in 30 days; 90 days, P < 0.001);
      however, EI had significantly higher odds of repeat anti-reflux procedures in the
      subsequent year (OR = 7.12, P < 0.001). DISCUSSIONS: Endoscopic injection
      constituted nearly half of initial anti-reflux procedures in children. However,
      patients treated with UNC had significantly lower odds of requiring re-treatment
      in the first year relative to those treated with EI. By contrast, patients
      treated with UNC had more than twice the odds of being readmitted or visiting an
      ER postoperatively. Although the available data were amongst the largest and most
      well validated, the major limitation was the retrospective nature of the
      administrative database. The practice setting may not be generalizable to states
      not included in the analysis. CONCLUSIONS: Postoperative readmissions and ER
      visits were uncommon after any surgical intervention for VUR, but were more
      common among children undergoing UNC. The EI patients had a more than seven-fold
      increased risk of surgical re-treatment within 1 year.

PMID- 28434636
TI  - Contralateral metachronous undescended testis: Is it predictable?
AB  - INTRODUCTION: Metachronous undescended testis (mcUDT), an acquired UDT after
      contralateral orchiopexy, can occur in some boys. If one were able to predict its
      occurrence, one might consider a proactive approach or at least one would be able
      to counsel the parents accordingly. Our hypothesis was there may be
      characteristics evident at the time of initial orchiopexy which could predict the
      development of contralateral mcUDT. OBJECTIVE: The aim was to Identify factors
      present at initial orchiopexy that predict development of subsequent mcUDT. STUDY
      DESIGN: Subjects were identified using the Current Procedural Terminology code
      for inguinal orchiopexy (54640). We included patients from January 1997 to
      October 2015. We included patients who underwent orchiopexy for unilateral UDT
      (uUDT). The study population consisted of patients who had undergone metachronous
      orchiopexies; controls were patients who were 17 years at time of data collection
      with a single orchiopexy. Cox proportional hazard regression was used to model
      the relationship between possible predictors of subsequent UDT using PROC PHREG
      with SAS Software 9.4. RESULTS: From 1035 eligible patients we identified 38 with
      mcUDT and 207 controls (uUDT). Median age at the first orchiopexy of mcUDT
      patients was 2.5 years (min/max, 0.50/10.4 years) and 8.2 years (min/max
      0.70/12.8 years) for uUDT, p < 0.0001. Subjects with a contralateral retractile
      testis on preoperative exam had a 4.2 times higher rate of subsequent UDT than
      patients with a contralateral descended testis (95% CI 2.077-8.353). The rate of
      mcUDT was 6.7 times higher if the testis was a retractile testis under anesthesia
      (95% CI 2.7-16.5) (Table). DISCUSSION: Contralateral retractile UDT was a
      significant predictor of mcUDT. We believe patients with a contralateral
      retractile testis at time of orchiopexy should be counseled on bilateral
      orchiopexy. The risks of complications with orchiopexy should be weighed against
      risks of a subsequent surgery and anesthesia event. CONCLUSION: A discussion of
      risks and benefits regarding bilateral orchiopexies should be undertaken with the
      parents prior to surgery in the setting of an UDT with contralateral retractile
      testis.

PMID- 28434637
TI  - Clinical heterogeneity in children with gonadal dysgenesis associated with non
      mosaic 46,XY karyotype.
AB  - INTRODUCTION: Gonadal dysgenesis is unique in disorders of sex development (DSD),
      in that it can be associated with 46,XX, 46,XY or mosaic 45,X/46,XY karyotypes.
      Gonadal dysgenesis can be partial or complete. Gonadal dysgenesis associated with
      the Y-chromosome has increased risk of gonadal germ cell neoplasms. Most of the
      literature focus on 45,X/46,XY gonadal dysgenesis, while there are scanty data on
      the condition when the karyotype is non-mosaic 46,XY. OBJECTIVE: To investigate
      the diversity of clinical pictures of children presenting with 46,XY DSD due to
      gonadal dysgenesis. METHODS: A retrospective study on consecutive patients
      diagnosed with 46,XY gonadal dysgenesis at age <=18 years in a tertiary center
      from 1985 to 2015. The clinical presentations, phenotypes, gonadal features and
      associated anomalies were investigated. RESULTS: Twenty-eight patients with Y
      chromosome gonadal dysgenesis were identified during the study period and six
      (21.4%) had non-mosaic 46,XY karyotype. Three had complete gonadal dysgenesis
      (CGD) with normal female phenotype, while the other three had partial gonadal
      dysgenesis (PGD). Of the three patients with CGD, two presented with the
      classical Swyer syndrome at adolescence, while the third presented at birth with
      multiple congenital anomalies. The three PGD patients presented with ambiguous
      genitalia at birth (n = 2), and isolated hypospadias (n = 1), which was
      associated with Frasier syndrome. Three patients had germ cell neoplasms:
      bilateral gonadoblastoma (n = 1), bilateral intratubular germ cell neoplasia
      unclassified (n = 1), and dysgerminoma + gonadoblastoma (n = 1). Two patients had
      global developmental delay with other congenital anomalies, and another patient
      had learning difficulties with borderline intelligence (Table). DISCUSSION: The
      findings suggest that 46,XY gonadal dysgenesis is much rarer than 45,X/46,XY
      gonadal dysgenesis. Patients differed in their clinical presentations and well
      established syndromes happened in half of them. Overall, the risk of germ cell
      neoplasms and the association with other somatic anomalies appeared to be high.
      The study was limited by: its small number, single-center experience, and the
      possibility of missing the diagnosis in some male patients with mild
      undervirilization. CONCLUSION: Heterogeneity was noted in the clinical,
      phenotypic and gonadal features among pediatric patients with 46,XY gonadal
      dysgenesis.

PMID- 28434638
TI  - Response to Letter to the Editor re 'Comparison of variables affecting the
      surgical outcome of tubularized and tubularized incised plate urethroplasty in
      adult and pediatric hypospadias'.

PMID- 28434639
TI  - Response to Letter to the Editor re 'Urinary Continence Outcomes Following
      Vaginoplasty in Patients with Congenital Adrenal Hyperplasia'.

PMID- 28434640
TI  - Imaging Guidance for Transcatheter Aortic Valve Replacement: Is Transoesophageal
      Echocardiography the Gold Standard?
AB  - Transcatheter aortic valve replacement (TAVR) is traditionally performed under
      cardiac imaging guidance. In the early TAVR experience, intra-procedural
      transoesophageal echocardiography (TOE) is recommended to guide device
      deployment, in the context of general anaesthesia (GA). Intra-procedural TOE
      imaging is particularly useful during TAVR deployment as a contrast-saving
      strategy for patients with renal impairment. Evidence has emerged recently
      demonstrating that in selected patients, transthoracic echocardiography (TTE) can
      be used to provide intra-procedural guidance for TAVR. Additionally, there is a
      growing body of evidence supporting the performance of TAVR using fluoroscopy
      alone, without additional cardiac imaging. This article aims to provide a
      contemporary review of the various procedural imaging approaches for TAVR
      guidance, comparing the relative strengths and weaknesses of each approach (Table
      1).

PMID- 28434641
TI  - Reply to "The value of troponin during an episode of acute heart failure in
      emergency department. One more reason to request it".

PMID- 28434642
TI  - [Late life depression or prodromal Alzheimer's disease: Which tools for the
      differential diagnosis?]
AB  - INTRODUCTION: Depression and Alzheimer's disease are both very frequent in
      elderly people. Cognitive deficits are the hallmark of Alzheimer's disease, but
      they are also common in depressed elderly people who often present cognitive
      deficits such as memory, attention and executive function problems. On the other
      hand, people with early Alzheimer's disease demonstrate emotional and behavioral
      disorders generally encountered in depression such as loss of energy, apathy,
      mood disorder, and irritability. Thus, in older adults with depression, the
      presence of cognitive deficits can make it difficult to distinguish cognitive
      decline that is associated with a depressive illness and the decline encountered
      in Alzheimer's disease because the clinical picture of the two disorders are
      similar. However, early distinction between the two disorders is very important
      from a prognostic and therapeutical point of view. OBJECTIVE: After a brief
      description of the relationship between depression and early Alzheimer's disease
      in elderly people, this paper aims to present an updated literature review of
      data on differential diagnoses between these disorders. METHOD: We performed a
      non-systematical, yet as exhaustive as possible, literature search with Pubmed
      electronic database, screening studies from 2000 to 2016. RESULTS: The majority
      of the studies concerned cognitive aspects, but only a few studies investigated
      others markers such as cerebral imaging, electroencephalography, cerebrospinal
      fluid markers. At the neuropsychological examination, a detailed analysis of the
      mnesic profile revealed a better benefit of semantic cueing in patients with late
      life depression in comparison to those with prodromal Alzheimer's disease and
      better performances in recognition memory. Moreover, longitudinal follow-up of
      patients with depression indicated that deficits in delayed recall memory, but
      not in executive functions, were associated with the subsequent development of
      Alzheimer's disease. Several studies showed that tests of executive functions
      could not differentiate between patients with late life depression and patients
      with prodromal Alzheimer's disease. A measure of global cognitive decline does
      not seem to be helpful in differentiating early Alzheimer's disease and
      depression, unlike an analysis of the neuropsychological profile on several
      composite scales, such as the Mini Mental State Examination. Furthermore, recent
      work has investigated the utility of olfactory or gustative markers with
      promising results and convenient tools for clinical practice. Concerning
      morphological brain imaging, only detailed volumetric analysis could show
      differences between the two diseases, but these techniques are not always
      available for clinical practice. It is the same for other recent techniques, such
      as quantitative electroencephalography, Near InfraRed Spectroscopy, Single Photon
      Emission Computed Tomography, or Transcranial Doppler Ultrasonography, which have
      received little attention so far as differential diagnostic tools. Finally,
      cerebrospinal fluid analysis could be useful, including beta amyloid levels.
      CONCLUSION: Despite numerous efforts in recent years, differential diagnosis of
      dementia from depression in the elderly remains difficult. Results of this review
      highlight the necessity of conducting more research in this area, with multi
      method studies, using not only cognitive analysis but also cerebral imaging
      techniques.

PMID- 28434643
TI  - Assessment of cell death mechanisms triggered by 177Lu-anti-CD20 in lymphoma
      cells.
AB  - The aim of this research was to evaluate the cell cycle redistribution and
      activation of early and late apoptotic pathways in lymphoma cells after treatment
      with 177Lu-anti-CD20. Experimental and computer models were used to calculate the
      radiation absorbed dose to cancer cell nuclei. The computer model (Monte Carlo,
      PENELOPE) consisted of twenty spheres representing cells with an inner sphere
      (cell nucleus) embedded in culture media. Radiation emissions of the
      radiopharmaceutical located in cell membranes and in culture media were
      considered for nuclei dose calculations. Flow cytometric analyses demonstrated
      that doses as low as 4.8Gy are enough to induce cell cycle arrest and activate
      late apoptotic pathways.

PMID- 28434644
TI  - Research priorities for a multi-center child abuse network: Lessons learned from
      pediatric emergency medicine networks.

PMID- 28434645
TI  - Comparison of Outcomes in Men Versus Women After Percutaneous Coronary
      Intervention for Chronic Total Occlusion.
AB  - Conflicting evidence exists on gender differences in outcomes after coronary
      stenting, and gender-based data in patients with chronic total occlusions (CTO)
      who underwent percutaneous coronary intervention (PCI) are scarce. Consecutive
      patients who underwent CTO PCI from January 2005 to December 2013 were included
      in the analysis and stratified according to gender. The primary outcome measure
      was all-cause mortality. Median follow-up was 2.6 years (interquartile range 1.1
      to 3.1). Of 2002 patients, 332 (17%) were women. Procedural success was achieved
      in 82% and 83% of women and men (p = 0.31). All-cause mortality was 15% and 11%
      in women and men (log-rank p = 0.17) with an adjusted hazard ratio of 0.85 (95%
      confidence interval [CI] 0.61 to 1.17, p = 0.31). All-cause mortality was
      significantly reduced in patients with procedural success, both in women (12% vs
      32%, adjusted hazard ratio 0.44, 95% CI 0.24 to 0.79, p = 0.006) and men (9% vs
      21%, adjusted hazard ratio 0.64, 95% CI 0.47 to 0.88, p = 0.006), with similar
      mortality benefits associated with successful revascularization in both groups
      (interaction p = 0.35). In conclusion, recanalization of coronary arterial CTO is
      equally successful in both women and men.

PMID- 28434646
TI  - Factors Determining Aortic Valve Dysfunction in Korean Subjects With a Bicuspid
      Aortic Valve.
AB  - Bicuspid aortic valve (BAV) disease has a male predominance of approximately 3:1
      and shows diverse presentations about aortic valve dysfunction. This study aimed
      to find independent determinants for significant aortic stenosis (AS) or
      significant aortic regurgitation (AR) in adults with BAV. We retrospectively
      investigated the medical records of 1,073 subjects (773 men, mean age 55 +/- 14
      years) who were first diagnosed with BAV disease by transthoracic
      echocardiography. We excluded 52 subjects with both significant AS and
      significant AR. Of the remaining 1,021 subjects, 418 (41%) presented with
      significant AS, 249 (24%) showed significant AR, and the rest of the subjects
      were grouped into a normal functioning BAV (n = 354, 35%). BAV morphology was
      classified into the following 4 types according to position and pattern of raphe
      and cusps: (1) fusion of the right and left coronary cusps (type 1), (2) fusion
      of the right and noncoronary cusps (type 2), (3) fusion of the left and
      noncoronary (type 3), and (4) no raphe (type 0). Patients with significant AS
      were older, more likely to be women than men, and had a higher prevalence of type
      0 BAV. Patients with significant AR were younger and were more likely to be men.
      In multivariate logistic regression analysis, women, older age, and type 0 or
      type 3 BAV were associated with significant AS. In contrast, men, hypertension,
      and chronic kidney disease were correlated with significant AR. Significant valve
      dysfunction in adults with first diagnosed BAV was closely associated with age,
      gender, and BAV morphology.

PMID- 28434647
TI  - Anemia at Hospital Admission and Its Relation to Outcomes in Patients With Heart
      Failure (from the Polish Cohort of 2 European Society of Cardiology Heart Failure
      Registries).
AB  - Anemia is a commonly observed co-morbidity in heart failure (HF). The aim of the
      study was to assess prevalence, risk factors for, and effect of anemia on short-
      and long-term outcomes in HF. The study included 1,394 Caucasian patients
      hospitalized for HF, with known hemoglobin concentration on hospital admission,
      participating in 2 HF registries of the European Society of Cardiology (Pilot and
      Long-Term). Anemia was defined as hemoglobin concentration of <13 g/dl for men
      and <12 g/dl for women. Primary end points were (1) all-cause death at 1 year and
      (2) a composite of all-cause death and rehospitalization for HF at 1 year.
      Secondary end points included inter alia death during index hospitalization. In
      addition, we investigated the effect of changes in hemoglobin concentration
      during hospitalization on prognosis. Anemia occurred in 33% of patients.
      Predictors of anemia included older age, diabetes, greater New York Heart
      Association class at hospital admission and kidney disease. During 1-year follow
      up, 21% of anemic and 13% of nonanemic patients died (p <0.0001). Combined
      primary end point occurred in 45% of anemic and in 33% of nonanemic patients (p
      <0.0001). Anemia was strongly predictive of all the prespecified clinical end
      points in univariate analyses but not in multivariate analyses. Changes in
      hemoglobin concentration during hospitalization had no effect on 1-year outcomes.
      In conclusion, anemia was present in 1/3 of patients with HF. Mild-to-moderate
      anemia seems more a marker of older age, worse clinical condition, and a higher
      co-morbidity burden, rather than an independent risk factor in HF.

PMID- 28434648
TI  - Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an
      open-label, non-comparative, phase 1/2 dose escalation and expansion trial.
AB  - BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the
      only approved drug worldwide, and outcomes remain poor. We aimed to assess the
      safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune
      checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or
      without chronic viral hepatitis. METHODS: We did a phase 1/2, open-label, non
      comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in
      adults (>=18 years) with histologically confirmed advanced hepatocellular
      carcinoma with or without hepatitis C or B (HCV or HBV) infection. Previous
      sorafenib treatment was allowed. A dose-escalation phase was conducted at seven
      hospitals or academic centres in four countries or territories (USA, Spain, Hong
      Kong, and Singapore) and a dose-expansion phase was conducted at an additional 39
      sites in 11 countries (Canada, UK, Germany, Italy, Japan, South Korea, Taiwan).
      At screening, eligible patients had Child-Pugh scores of 7 or less (Child-Pugh A
      or B7) for the dose-escalation phase and 6 or less (Child-Pugh A) for the dose
      expansion phase, and an Eastern Cooperative Oncology Group performance status of
      1 or less. Patients with HBV infection had to be receiving effective antiviral
      therapy (viral load <100 IU/mL); antiviral therapy was not required for patients
      with HCV infection. We excluded patients previously treated with an agent
      targeting T-cell costimulation or checkpoint pathways. Patients received
      intravenous nivolumab 0.1-10 mg/kg every 2 weeks in the dose-escalation phase
      (3+3 design). Nivolumab 3 mg/kg was given every 2 weeks in the dose-expansion
      phase to patients in four cohorts: sorafenib untreated or intolerant without
      viral hepatitis, sorafenib progressor without viral hepatitis, HCV infected, and
      HBV infected. Primary endpoints were safety and tolerability for the escalation
      phase and objective response rate (Response Evaluation Criteria In Solid Tumors
      version 1.1) for the expansion phase. This study is registered with
      ClinicalTrials.gov, number NCT01658878. FINDINGS: Between Nov 26, 2012, and Aug
      8, 2016, 262 eligible patients were treated (48 patients in the dose-escalation
      phase and 214 in the dose-expansion phase). 202 (77%) of 262 patients have
      completed treatment and follow-up is ongoing. During dose escalation, nivolumab
      showed a manageable safety profile, including acceptable tolerability. In this
      phase, 46 (96%) of 48 patients discontinued treatment, 42 (88%) due to disease
      progression. Incidence of treatment-related adverse events did not seem to be
      associated with dose and no maximum tolerated dose was reached. 12 (25%) of 48
      patients had grade 3/4 treatment-related adverse events. Three (6%) patients had
      treatment-related serious adverse events (pemphigoid, adrenal insufficiency,
      liver disorder). 30 (63%) of 48 patients in the dose-escalation phase died (not
      determined to be related to nivolumab therapy). Nivolumab 3 mg/kg was chosen for
      dose expansion. The objective response rate was 20% (95% CI 15-26) in patients
      treated with nivolumab 3 mg/kg in the dose-expansion phase and 15% (95% CI 6-28)
      in the dose-escalation phase. INTERPRETATION: Nivolumab had a manageable safety
      profile and no new signals were observed in patients with advanced hepatocellular
      carcinoma. Durable objective responses show the potential of nivolumab for
      treatment of advanced hepatocellular carcinoma. FUNDING: Bristol-Myers Squibb.

PMID- 28434649
TI  - Immune oncology in hepatocellular carcinoma-hype and hope.

PMID- 28434651
TI  - Neonatal sepsis.
AB  - Neonatal sepsis is the cause of substantial morbidity and mortality. Precise
      estimates of neonatal sepsis burden vary by setting. Differing estimates of
      disease burden have been reported from high-income countries compared with
      reports from low-income and middle-income countries. The clinical manifestations
      range from subclinical infection to severe manifestations of focal or systemic
      disease. The source of the pathogen might be attributed to an in-utero infection,
      acquisition from maternal flora, or postnatal acquisition from the hospital or
      community. The timing of exposure, inoculum size, immune status of the infant,
      and virulence of the causative agent influence the clinical expression of
      neonatal sepsis. Immunological immaturity of the neonate might result in an
      impaired response to infectious agents. This is especially evident in premature
      infants whose prolonged stays in hospital and need for invasive procedures place
      them at increased risk for hospital-acquired infections. Clinically, there is
      often little difference between sepsis that is caused by an identified pathogen
      and sepsis that is caused by an unknown pathogen. Culture-independent
      diagnostics, the use of sepsis prediction scores, judicious antimicrobial use,
      and the development of preventive measures including maternal vaccines are
      ongoing efforts designed to reduce the burden of neonatal sepsis.

PMID- 28434652
TI  - Multifetal reduction of triplets to twins compared with non-reduced twins: a meta
      analysis.
AB  - The current systematic review and meta-analysis evaluates the perinatal outcomes
      in twin pregnancies following multifetal pregnancy reduction (MPR) compared with
      non-reduced twins. We considered all studies comparing perinatal outcomes of twin
      pregnancies following MPR to non-reduced twin pregnancies. Our search yielded 639
      publications, of which 91 were assessed for eligibility. A total of 22 studies
      met our inclusion criteria. Overall, fetal reduction of triplets to twins
      resulted in comparable perinatal outcomes to non-reduced twins with regards to
      gestational age and birthweight at delivery, pregnancy loss prior to 24 weeks, as
      well as the development of gestational diabetes and hypertensive disorders of
      pregnancy. Of all outcomes, only the Caesarean section rate was significantly
      higher in the MPR group compared with the non-reduced twins group with an odds
      ratio of 1.95 (95% confidence interval 1.33-2.87). This meta-analysis suggests
      that MPR of triplet pregnancies to twins is associated with comparable perinatal
      outcomes to that of non-reduced twins. This information can further help in
      guiding, and probably reassuring, clinician and patient decision-making when
      faced with high-order multifetal pregnancies.

PMID- 28434650
TI  - Global kidney health 2017 and beyond: a roadmap for closing gaps in care,
      research, and policy.
AB  - The global nephrology community recognises the need for a cohesive plan to
      address the problem of chronic kidney disease (CKD). In July, 2016, the
      International Society of Nephrology hosted a CKD summit of more than 85 people
      with diverse expertise and professional backgrounds from around the globe. The
      purpose was to identify and prioritise key activities for the next 5-10 years in
      the domains of clinical care, research, and advocacy and to create an action plan
      and performance framework based on ten themes: strengthen CKD surveillance;
      tackle major risk factors for CKD; reduce acute kidney injury-a special risk
      factor for CKD; enhance understanding of the genetic causes of CKD; establish
      better diagnostic methods in CKD; improve understanding of the natural course of
      CKD; assess and implement established treatment options in patients with CKD;
      improve management of symptoms and complications of CKD; develop novel
      therapeutic interventions to slow CKD progression and reduce CKD complications;
      and increase the quantity and quality of clinical trials in CKD. Each group
      produced a prioritised list of goals, activities, and a set of key deliverable
      objectives for each of the themes. The intended users of this action plan are
      clinicians, patients, scientists, industry partners, governments, and advocacy
      organisations. Implementation of this integrated comprehensive plan will benefit
      people who are at risk for or affected by CKD worldwide.

PMID- 28434653
TI  - A revised prediction model for natural conception.
AB  - One of the aims in reproductive medicine is to differentiate between couples that
      have favourable chances of conceiving naturally and those that do not. Since the
      development of the prediction model of Hunault, characteristics of the subfertile
      population have changed. The objective of this analysis was to assess whether
      additional predictors can refine the Hunault model and extend its applicability.
      Consecutive subfertile couples with unexplained and mild male subfertility
      presenting in fertility clinics were asked to participate in a prospective cohort
      study. We constructed a multivariable prediction model with the predictors from
      the Hunault model and new potential predictors. The primary outcome, natural
      conception leading to an ongoing pregnancy, was observed in 1053 women of the
      5184 included couples (20%). All predictors of the Hunault model were selected
      into the revised model plus an additional seven (woman's body mass index, cycle
      length, basal FSH levels, tubal status,history of previous pregnancies in the
      current relationship (ongoing pregnancies after natural conception, fertility
      treatment or miscarriages), semen volume, and semen morphology. Predictions from
      the revised model seem to concur better with observed pregnancy rates compared
      with the Hunault model; c-statistic of 0.71 (95% CI 0.69 to 0.73) compared with
      0.59 (95% CI 0.57 to 0.61).

PMID- 28434654
TI  - Compulsive Addiction-like Aggressive Behavior in Mice.
AB  - BACKGROUND: Some people are highly motivated to seek aggressive encounters, and
      among those who have been incarcerated for such behavior, recidivism rates are
      high. These observations echo two core features of drug addiction: high
      motivation to seek addictive substances, despite adverse consequences, and high
      relapse rates. Here we used established rodent models of drug addiction to
      determine whether they would be sensitive to "addiction-like" features of
      aggression in CD-1 mice. METHODS: In experiments 1 and 2, we trained older CD-1
      mice to lever press for opportunities to attack younger C57BL6/J mice. We then
      tested them for relapse to aggression seeking after forced abstinence or
      punishment-induced suppression of aggression self-administration. In experiment
      3, we trained a large cohort of CD-1 mice and tested them for choice-based
      voluntary suppression of aggression seeking, relapse to aggression seeking,
      progressive ratio responding, and punishment-induced suppression of aggression
      self-administration. We then used cluster analysis to identify patterns of
      individual differences in compulsive "addiction-like" aggressive behavior.
      RESULTS: In experiments 1 and 2, we observed strong motivation to acquire operant
      self-administration of opportunities to aggress and relapse vulnerability during
      abstinence. In experiment 3, cluster analysis of the aggression-related measures
      identified a subset of "addicted" mice (~19%) that exhibited intense operant
      reinforced attack behavior, decreased likelihood to select an alternative
      reinforcer over aggression, heightened relapse vulnerability and progressive
      ratio responding, and resilience to punishment-induced suppression of aggressive
      behavior. CONCLUSIONS: Using procedures established to model drug addiction, we
      showed that a subpopulation of CD-1 mice demonstrate "addiction-like" aggressive
      behavior, suggesting an evolutionary origin for compulsive aggression.

PMID- 28434656
TI  - An overview of EU and USA intestinal transplant current activity.
AB  - AIM OF THE STUDY: To report the current activity of intestinal transplantation in
      Europe (EU) and Unites States of America (USA), underlining outcomes in the last
      5 years and discussing possible trends. PATIENTS AND METHODS: Data review of
      results was performed through analysis of ITR and UNOS registries, Eurotransplant
      and newsletter transplant reports, congress abstracts, international published
      literature, personal communications and hospital web sites. RESULTS: The absence
      in Europe of a sole organization collecting donors and the presence of many low
      volume centers (less than 5 cases/year) makes the difference with USA: in the
      last 5 years (2010-2014), 222 intestinal/multivisceral transplants have been
      performed in EU countries (most of them in the UK), while in USA, the number of
      transplants achieved 634 procedures in the same period of time. Waiting list
      mortality remains unacceptable in both continents. Improved short-term results,
      with over 80% survival at 1 year, have been achieved in the busiest transplant
      centers likely due to immune-induction agents, more recently to innovative cross
      match strategies and optimizing organ allocation, but long term outcomes are
      still inferior to other organ transplants. Most long-term survivors were
      reintegrated to society with self-sustained socioeconomic status. The economic
      burden for the society is high and related costs are different between USA and EU
      (and inside Europe between member state's health-care systems), but cost
      effectiveness for intestinal transplantation still needs to be proved.
      CONCLUSION: Overall intestinal transplantation continues to develop in EU and USA
      together with surgical and medical rehabilitation of patients affected by short
      gut syndrome.

PMID- 28434657
TI  - Corrigendum to "Human GRIN2B variants in neurodevelopmental disorders" [J
      Pharmacol Sci 132 (2) 115-121].

PMID- 28434655
TI  - Apolipoprotein E, Receptors, and Modulation of Alzheimer's Disease.
AB  - Apolipoprotein E (apoE) is a lipid carrier in both the peripheral and the central
      nervous systems. Lipid-loaded apoE lipoprotein particles bind to several cell
      surface receptors to support membrane homeostasis and injury repair in the brain.
      Considering prevalence and relative risk magnitude, the epsilon4 allele of the
      APOE gene is the strongest genetic risk factor for late-onset Alzheimer's disease
      (AD). ApoE4 contributes to AD pathogenesis by modulating multiple pathways,
      including but not limited to the metabolism, aggregation, and toxicity of amyloid
      beta peptide, tauopathy, synaptic plasticity, lipid transport, glucose
      metabolism, mitochondrial function, vascular integrity, and neuroinflammation.
      Emerging knowledge on apoE-related pathways in the pathophysiology of AD presents
      new opportunities for AD therapy. We describe the biochemical and biological
      features of apoE and apoE receptors in the central nervous system. We also
      discuss the evidence and mechanisms addressing differential effects of apoE
      isoforms and the role of apoE receptors in AD pathogenesis, with a particular
      emphasis on the clinical and preclinical studies related to amyloid-beta
      pathology. Finally, we summarize the current strategies of AD therapy targeting
      apoE, and postulate that effective strategies require an apoE isoform-specific
      approach.

PMID- 28434658
TI  - Feasibility of Ultrasound-Based Computational Fluid Dynamics as a Mitral Valve
      Regurgitation Quantification Technique: Comparison with 2-D and 3-D Proximal
      Isovelocity Surface Area-Based Methods.
AB  - Current Doppler echocardiography quantification of mitral regurgitation (MR)
      severity has shortcomings. Proximal isovelocity surface area (PISA)-based
      methods, for example, are unable to account for the fact that ultrasound Doppler
      can measure only one velocity component: toward or away from the transducer. In
      the present study, we used ultrasound-based computational fluid dynamics (Ub-CFD)
      to quantify mitral regurgitation and study its advantages and disadvantages
      compared with 2-D and 3-D PISA methods. For Ub-CFD, patient-specific mitral valve
      geometry and velocity data were obtained from clinical ultrasound followed by 3-D
      CFD simulations at an assumed flow rate. We then obtained the average ratio of
      the ultrasound Doppler velocities to CFD velocities in the flow convergence
      region, and scaled CFD flow rate with this ratio as the final measured flow rate.
      We evaluated Ub-CFD, 2-D PISA and 3-D PISA with an in vitro flow loop, which
      featured regurgitation flow through (i) a simplified flat plate with round
      orifice and (ii) a 3-D printed realistic mitral valve and regurgitation orifice.
      The Ub-CFD and 3-D PISA methods had higher precision than the 2-D PISA method. Ub
      CFD had consistent accuracy under all conditions tested, whereas 2-D PISA had the
      lowest overall accuracy. In vitro investigations indicated that the accuracy of 2
      D and 3-D PISA depended significantly on the choice of aliasing velocity.
      Evaluation of these techniques was also performed for two clinical cases, and the
      dependency of PISA on aliasing velocity was similarly observed. Ub-CFD was
      robustly accurate and precise and has promise for future translation to clinical
      practice.

PMID- 28434659
TI  - HPV-related oropharyngeal carcinoma de-escalation protocols.

PMID- 28434661
TI  - Retrospective Review of Percutaneous Image-Guided Ablation of Oligometastatic
      Prostate Cancer: A Single-Institution Experience.
AB  - PURPOSE: To retrospectively review and report the efficacy and safety of
      percutaneous image-guided ablation (cryoablation or radiofrequency ablation) in
      the treatment of oligometastatic prostate cancer. MATERIALS AND METHODS: An
      institutional registry was retrospectively reviewed and revealed 16 patients with
      oligometastatic prostate cancer (median age, 67 y; range, 50-86 y) who underwent
      percutaneous image-guided ablation to treat 18 metastatic sites. A subgroup of 7
      patients with 8 metastases were androgen-deprivation therapy (ADT)-naive and
      underwent ablation to delay initiation of ADT. Local tumor control, progression
      free survival (PFS), ADT-free survival, and procedural complications were
      analyzed. RESULTS: Local tumor control was achieved in 15 of 18 metastases (83%)
      at a median follow-up of 27 months (range, 5-56 mo). Local tumor recurrence was
      found in 3 of 18 metastases (17%), with a median time to local recurrence of 3.5
      months (range, 3-38 mo). Estimated PFS rates at 12 and 24 months were 56% (95%
      confidence interval [CI], 30%-76%) and 43% (95% CI, 19%-65%), respectively. In
      the 7 ADT-naive patients, local tumor control was achieved in all metastases, and
      the median ADT-free survival period was 29 months. There were no major procedural
      complications. CONCLUSIONS: In this cohort of patients with oligometastatic
      prostate cancer, percutaneous image-guided ablation was feasible and well
      tolerated and achieved acceptable local tumor control rates. Percutaneous
      ablation may be of particular utility in patients who wish to delay initiation of
      ADT.

PMID- 28434662
TI  - Paclitaxel-Coated Balloons for the Treatment of Symptomatic Central Venous
      Stenosis in Dialysis Access: Results from a Randomized Controlled Trial.
AB  - PURPOSE: To compare the clinically-assessed intervention-free period (IFP) of
      paclitaxel-coated balloon (PCB) vs conventional balloon angioplasty (CBA) for the
      treatment of symptomatic central venous stenosis (CVS) in dialysis access.
      MATERIALS AND METHODS: Within 20 months, 40 dialysis patients (19/40
      arteriovenous fistulae [AVFs] and 21/40 arteriovenous grafts [AVGs]) were
      randomized to undergo angioplasty either with a PCB (PCB group, n = 20; 14/20
      male; age: 56.7) or CBA (CBA group, n = 20; 15/20 male; age: 57). There were
      15/20 restenotic lesions in PCB group and 12/20 in CBA group. In 25/40 cases,
      patients had an ipslateral catheter insertion in the past. Primary endpoint was
      clinically-assessed intervention-free period (IFP) of the treated segment at 6
      months, while secondary endpoints included complication rates during follow-up
      period and identification of factors influencing IFP. RESULTS: Median IFP was
      significantly better in PCB group (PCB group: 179 days, vs CBA group: 124.5 days,
      P = .026). Mean follow-up period was 180 days (range, 5-479). There was no
      significant difference between AVGs and AVFs (P = .17), treatment of de novo vs
      restenotic lesions (P = .33), or prior presence of catheter insertion (P = .21).
      No complications were observed. In restenotic lesions in PCB group, longitudinal
      comparison between treatments also showed a significant difference in favor of
      PCB treatment (median IFP in PCB* group 177 vs 91 days in CBA* group; P = .01).
      CONCLUSIONS: In this prospective study, PCB had significantly better results
      compared with CBA for the treatment of symptomatic central venous stenosis in
      dialysis access. Retrospective longitudinal comparison of treatments in the same
      patients also showed a significant difference in favor of PCBs.

PMID- 28434663
TI  - Evaluation of toxic elements As, Cd, Cr, Cu, Ni, Pb and Zn in the surficial
      sediments of the Red Sea (Saudi Arabia).

PMID- 28434660
TI  - Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell
      carcinoma of the oropharynx: a single-arm, phase 2 study.
AB  - BACKGROUND: Head and neck cancers positive for human papillomavirus (HPV) are
      exquisitely radiosensitive. We investigated whether chemoradiotherapy with
      reduced-dose radiation would maintain survival outcomes while improving
      tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS: We
      did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling
      patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell
      carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod
      performance status scores of 0 or 1. Patients received two cycles of induction
      chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the
      curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy
      with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly.
      Complete or partial responders to induction chemotherapy received 54 Gy in 27
      fractions, and those with less than partial or no responses received 60 Gy in 30
      fractions. The primary endpoint was progression-free survival at 2 years,
      assessed in all eligible patients who completed protocol treatment. This study is
      registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195.
      FINDINGS: Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with
      a median age of 60 years (IQR 54-67). One patient did not receive treatment and
      44 were included in the analysis. 24 (55%) patients with complete or partial
      responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with
      less than partial responses received 60 Gy. Median follow-up was 30 months (IQR
      26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant
      metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of
      44 patients had grade 3 adverse events, but no grade 4 events were reported. The
      most common grade 3 events during induction chemotherapy were leucopenia (17
      [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia
      (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a
      gastrostomy tube at 3 months and none was dependent 6 months after treatment.
      INTERPRETATION: Chemoradiotherapy with radiation doses reduced by 15-20% was
      associated with high progression-free survival and an improved toxicity profile
      compared with historical regimens using standard doses. Radiotherapy de
      escalation has the potential to improve the therapeutic ratio and long-term
      function for these patients. FUNDING: University of California.

PMID- 28434664
TI  - Marine debris in beaches of the Southwestern Atlantic: An assessment of their
      abundance and mass at different spatial scales in northern coastal Argentina.
AB  - Argentina is currently undergoing an intensive development of coastal-oriented
      tourism due to the temperate climate and coastal sceneries of the Southwestern
      Atlantic and particularly its wide ocean-open sandy beaches, which may turn into
      an important contributor of marine debris to the beaches. This study was designed
      to assess at four spatial scales (i) the variation of the abundance and mass of
      marine debris and (ii) the composition and sources of these items in sandy
      tourist beaches of coastal zones of the province of Buenos Aires, in northern
      Argentina. The abundance and mass of marine debris shifted between sampling
      localities (separated by ~1.5*105m) and beaches (~3*104m). Debris was primarily
      from recreational and fishing activities and over 20mm in size. Tackling the
      complications associated with marine debris in northern Argentina may include
      intensive educational and advertising campaigns oriented chiefly to beach users
      and fisherman.

PMID- 28434665
TI  - Eutrophication, harmful algae and biodiversity - Challenging paradigms in a world
      of complex nutrient changes.
AB  - Eutrophication is a complex process and often associated with not only a change
      in overall algal biomass but also with a change in biodiversity. Common metrics
      of eutrophication (e.g., chlorophyll a), total nitrogen (TN) and phosphorus (TP)
      are not adequate for understanding biodiversity changes, especially those
      associated with harmful algal bloom (HAB) proliferations. Harmful algae can
      increase disproportionately with eutrophication, depending on which nutrients
      change and in what proportion. This paper challenges several classic paradigms in
      our understanding of eutrophication and associated biodiversity changes. The
      underlying message is that nutrient proportions and forms can alter biodiversity,
      even when nutrients are at concentrations in excess of those considered limiting.
      The global HAB problem is on a trajectory for more blooms, more toxins, more
      often, in more places. Our approach to management of HABs and eutrophication must
      consider the broader complexity of nutrient effects at scales ranging from
      physiological to ecological.

PMID- 28434666
TI  - Heavy metal distribution and contamination status in the sedimentary environment
      of Cochin estuary.
AB  - Heavy metals (Fe, Mn, Cr, Zn, Ni, Pb, Cu, Co and Cd) in the surface sediments of
      Cochin estuary, Southwest coast of India were analyzed to understand the spatio
      temporal variation and contamination status via six sampling campaigns. Pollution
      indices like enrichment factor, geoaccumulation index and pollution load index
      inferred that the sediments of the northern arm of the estuary exhibited severe
      trace metal accumulation. Numerical sediment quality guidelines were applied to
      assess adverse biological effects of the trace metals, suggesting that occasional
      biological effect may occur due to Cr, Cu, Ni and Pb. Correlations between
      metals, organic carbon, silt and clay suggested that both fine grained sediment
      and organic matter were important carriers for these metals. Multivariate
      statistics indicated that the sources of Cu and Ni resulted primarily from
      natural weathering processes, whereas enriched levels of Cd, Cr, Zn and Pb were
      mainly attributed to anthropogenic activities.

PMID- 28434667
TI  - Sedimentary heavy metal(loid) contamination in the Veracruz shelf, Gulf of
      Mexico: A baseline survey from a rapidly developing tropical coast.
AB  - This study examines sediment texture, geochemistry and sediment accumulation in
      cores from four sites in the Veracruz shelf area of the Gulf of Mexico, to assess
      the inputs of heavy metal(loid)s (and their potential biological impacts) in this
      carbonate-dominated shelf system, and to examine the rate of sedimentation near
      to the mouths of the La Antigua and Jamapa Rivers. The use of different pollution
      indices showed enrichment with Pb in all cores studied, although based on
      sediment quality guidelines As was the only element that has potential to
      occasionally cause damage to the benthic organisms present in the area. Heavy
      metal(loid) and sediment input from terrestrial and coastal sources is limited
      compared to more proximal, near-shore areas. The sediment core data presented
      however give a baseline dataset for heavy metal(loid) concentrations in the
      Veracruz shelf, against which future anthropogenic inputs can be assessed.

PMID- 28434668
TI  - Parasite infection and immune and health-state in wild fish exposed to marine
      pollution.
AB  - Association between parasitism and immunity and health-state was investigated in
      wild Sebastes oculatus after having determined that pollution exposure is
      associated with altered immune and health-state parameters. Given the importance
      of the immune system in antiparasite defense we predicted: (i) parasite infection
      would be higher in pollution-exposed than in control fish and (ii) fish with
      lower immune and health-state parameters would show higher parasitism than fish
      in better condition. Metazoan parasite fauna was compared between pollution
      exposed and non-exposed fish and parasitic indices were correlated with
      integrated measures of immunity and health-state. Results provided little support
      for the predictions; some parasite taxa increased, some decreased, and some were
      not affected in pollution-exposed fish despite their altered health and immunity.
      Furthermore, there was no link between individual immune and health-state
      parameters and parasitism. These findings highlight the complexity of host
      parasite-environment interactions in relation to pollution in natural marine
      ecosystems.

PMID- 28434669
TI  - Diurnal variation of CO2, CH4, and N2O emission fluxes continuously monitored in
      situ in three environmental habitats in a subtropical estuarine wetland.
AB  - Wetlands play a crucial role in modulating atmospheric concentrations of
      greenhouse gases (GHGs) such as carbon dioxide (CO2), methane (CH4), and nitrous
      oxide (N2O). The key factors controlling GHG emission from subtropical estuarine
      wetlands were investigated in this study, which continuously monitored the
      uptake/emission of GHGs (CO2, CH4, and N2O) by/from a subtropical estuarine
      wetland located in the Minjiang estuary in the coastal region of southeastern
      China. A self-designed floating chamber was used to collect air samples on-site
      at three environmental habitats (Phragmites australis marsh, mudflats, and river
      water). The CO2, CH4, and N2O concentrations were then measured using an
      automated nondispersive infrared analyzer. The magnitudes of the CO2 and N2O
      emission fluxes at the three habitats were ordered as river water>P.
      australis>mudflats. P. australis emitted GHGs through photosynthesis and
      respiration processes. Emissions of CH4 from P. australis and the mudflats were
      revealed to be slightly higher than those from the river water. The total GHG
      emission fluxes at the three environmental habitats were quite similar (4.68
      4.78gm-2h-1). However, when the total carbon dioxide equivalent fluxes (CO2-e)
      were considered, the river water was discovered to emit the most CO2-e compared
      with P. australis and the mudflats. Based on its potential to increase global
      warming, N2O was the main contributor to the total GHG emission, with that
      emitted from the river water being the most considerable. Tidal water carried
      onto the marsh had its own GHG content and thus has acted as a source or sink of
      GHGs. However, water quality had a large effect on GHG emissions from the river
      water whereas the tidal water height did not. Both high salinity and large
      amounts of sulfates in the wetlands explicitly inhibited the activity of CH4
      producing bacteria, particularly at nighttime.

PMID- 28434670
TI  - Real-time eutrophication status evaluation of coastal waters using support vector
      machine with grid search algorithm.
AB  - The development of techniques for real-time monitoring of the eutrophication
      status of coastal waters is of great importance for realizing potential cost
      savings in coastal monitoring programs and providing timely advice for marine
      health management. In this study, a GS optimized SVM was proposed to model
      relationships between 6 easily measured parameters (DO, Chl-a, C1, C2, C3 and C4)
      and the TRIX index for rapidly assessing marine eutrophication states of coastal
      waters. The good predictive performance of the developed method was indicated by
      the R2 between the measured and predicted values (0.92 for the training dataset
      and 0.91 for the validation dataset) at a 95% confidence level. The
      classification accuracy of the eutrophication status was 86.5% for the training
      dataset and 85.6% for the validation dataset. The results indicated that it is
      feasible to develop an SVM technique for timely evaluation of the eutrophication
      status by easily measured parameters.

PMID- 28434671
TI  - Resveratrol improves mitochondrial function in the remnant kidney from 5/6
      nephrectomized rats.
AB  - Mitochondrial dysfunction is involved in the pathogenesis of chronic kidney
      disease (CKD). Resveratrol has been demonstrated to be beneficial for the
      recovery of kidney diseases. In this study, the 5/6 nephrectomized rat was used
      as a CKD model and the TGF-beta1-exposed mouse mesangial cells were used as an in
      vitro model. Pathological examination showed that resveratrol treatment
      attenuated glomerular injury in the remnant kidney of 5/6 nephrectomized rat.
      Additionally, resveratrol improved mitochondrial function in vivo and in vitro,
      as evidenced by increasing mitochondrial membrane potential, increasing ATP,
      decreasing reactive oxygen species production and enhancing activities of complex
      I and III. Furthermore, the dysregulated expressions of electron transport chain
      proteins and fission/fusion proteins in the kidney of 5/6 nephrectomize rats and
      TGF-beta1-exposed mesangial cells were restored by resveratrol. Finally,
      upregulated sirt1 and PGC-1alpha deacetylation were found after treatment with
      resveratrol in vivo and in vitro, which may contribute to the mitochondrial
      protective effects of resveratrol. The results demonstrate that resveratrol
      protects the mitochondria of kidney in 5/6 nephrectomized rats and TGF-beta1
      induced mesangial cells. The study provides new insights into the renoprotective
      mechanisms of resveratrol.

PMID- 28434672
TI  - Women's attitudes towards the medicalization of childbirth and their associations
      with planned and actual modes of birth.
AB  - PROBLEM: Rates of medical interventions in childbirth have greatly increased in
      the Western world. BACKGROUND: Women's attitudes affect their birth choices. AIM:
      To assess women's attitudes towards the medicalization of childbirth and their
      associations with women's background as well as their fear of birth and planned
      and unplanned modes of birth. METHODS: This longitudinal observational study
      included 836 parous woman recruited at women's health centres and natural birth
      communities in Israel. All women filled in questionnaires about attitudes towards
      the medicalization of childbirth, fear of birth, and planned birth choices. Women
      at <28 weeks gestation when filling in the questionnaire were asked to fill in a
      second one at ~34 weeks. Phone follow-up was conducted ~6 weeks postpartum to
      assess actual mode of birth. FINDINGS: Attitudes towards medicalization were more
      positive among younger and less educated women, those who emigrated from the
      former Soviet Union, and those with a more complicated obstetric background.
      Baseline attitudes did not differ by parity yet became less positive throughout
      pregnancy only for primiparae. More positive attitudes were related to greater
      fear of birth. The attitudes were significantly associated with planned birth
      choices and predicted emergency caesareans and instrumental births. DISCUSSION:
      Women form attitudes towards the medicalization of childbirth which may still be
      open to change during the first pregnancy. More favourable attitudes are related
      to more medical modes of birth, planned and unplanned. CONCLUSION: Understanding
      women's views of childbirth medicalization may be key to understanding their
      choices and how they affect labour and birth.

PMID- 28434673
TI  - Factors influencing midwives' use of an evidenced based Normal Birth Guideline.
AB  - Problem or issue: Rates of elective and unplanned caesarean sectioncontinue to
      increase in high income countries. Evidence-based clinical guidelines aim to
      promote andsupport normal birth but are rarely evaluated. What is already known:
      The Queensland Normal Birth Guideline was developed inconsultation with
      stakeholders and disseminated to publicand private hospitals and released in
      2012. Impact of theGuideline on practice has not been investigated. What this
      paper adds: Although most midwives (90%) were aware of theguideline, only 71%
      reported that it routinely guidedpractice.

PMID- 28434674
TI  - Transcriptome analysis of the brain of the sea bream (Sparus aurata) after
      exposure to human pharmaceuticals at realistic environmental concentrations.
AB  - Human pharmaceuticals such as Acetaminophen, Atenolol and Carbamazepine are
      pseudo persistent aquatic pollutants with yet unknown sub-lethal effects at
      environmentally relevant concentrations. Gilthead seabream (Sparus aurata) were
      exposed to Acetaminophen: 31.90 +/- 11.07 MUg L-1; Atenolol: 0.95 +/- 0.38 MUg L
      1 and Carbamazepine: 6.95 +/- 0.13 MUg L-1 in a 28 day flow through experiment to
      (1) determine whether exposure to low concentrations in the MUg.L-1 range of the
      pharmaceuticals alters the brain transcriptome and, (2) identify different
      expression profiles and treatment specific modes of action and pathways. Despite
      low exposure concentrations, 411, 7 and 612 differently expressed transcripts
      were identified in the individual treatments with Acetaminophen, Atenolol and
      Carbamazepine, respectively. Functional analyses of differentially expressed
      genes revealed a significant over representation of several biological processes,
      cellular compartment features and molecular functions for both Acetaminophen and
      Carbamazepine treatments. Overall, the results obtained in seabream brain suggest
      similar physiological responses to those observed in humans also at environmental
      concentrations, as well as the existence of treatment specific processes that may
      be useful for the development of biomarkers of contamination.

PMID- 28434675
TI  - CADASIL as a Useful Medical Model and Genetic Form of Vascular Depression.
AB  - OBJECTIVE: The main magnetic resonance imaging (MRI) findings of cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL) are white matter hyperintensities (WMHs), lacunar infarctions, and
      cerebral microbleeds (CMBs). The purpose of this study was to investigate the
      effects of these three neuroimaging markers of CADASIL on depression to determine
      whether CADASIL is a useful medical model supporting the vascular depression
      hypothesis. METHODS: Eighty-four subjects with CADASIL, aged 34-86 years,
      participated in this study. They underwent comprehensive clinical evaluation,
      including 3T MRI and genotyping of NOTCH3. The effects of WMH, lacunar
      infarctions, and CMBs were analyzed by path analyses and multivariate logistic
      regression analyses. RESULTS: Patients with CADASIL exhibited frequencies of
      17.9% for major depressive disorder (MDD) and 10.7% for minor depressive
      disorder. The frequency of MDD increased from 5.0% to 46.2% as WMH volume
      increased from first quartile to fourth quartile. WMH volume (OR: 1.03, 95% CI:
      1.003-1.06) in patients with CADASIL was associated with the current depressive
      disorder. Path analyses demonstrated that only WMH volume was associated with the
      Korean version of the short form Geriatric Depression Scale score, Center for
      Epidemiologic Studies Depression Scale score, and 17-item Hamilton depression
      scale score. The effects of lacunar infarctions and CMBs on depression were not
      significant in path analyses and multivariate logistic regression analyses.
      CONCLUSIONS: This study demonstrates that WMHs are closely associated with
      depression in patients with CADASIL. This supports that CADASIL might be a useful
      medical model and genetic form of vascular depression.

PMID- 28434676
TI  - Meta-analysis of Results of Testosterone Therapy on Sexual Function Based on
      International Index of Erectile Function Scores.
AB  - CONTEXT: The interpretation of available clinical evidence related to the effect
      of testosterone (T) treatment (TTh) on sexual function has been inconsistent, in
      part due to the use of different and self-reported measures to assess outcomes.
      The International Index of Erectile Function (IIEF) is the most frequently used
      validated tool to assess male sexual function. OBJECTIVE: To perform a meta
      analysis of available data evaluating the effect of TTh on male sexual function
      using IIEF as the primary outcome. EVIDENCE ACQUISITION: An extensive Medline,
      Embase, and Cochrane search was performed including all placebo-controlled
      randomized clinical trials enrolling men comparing the effect of TTh on sexual
      function. EVIDENCE SYNTHESIS: Out of 137 retrieved articles, 14 were included in
      the study enrolling 2298 participants, with a mean follow-up of 40.1 wk and mean
      age of 60.2+/-6.5 yr. Using IIEF-erectile function domain (IIEF-EFD) as the
      outcome, we found that TTh significantly improved erectile function compared with
      placebo (mean difference=2.31 [1.41;3.22] IIEF-EFD score, p<0.0001). Patients
      with more severe hypogonadism (total T<8 nmol/l) reported greater changes in
      final IIEF-EFD score when compared with those with a milder T deficiency (total
      T<12 nmol/l; 1.47 [0.90;2.03] and 2.95 [1.86;4.03] for total T<12 nmol/l and <8
      nmol/l, respectively, Q=5.61, p=0.02). The magnitude of the effect was lower in
      the presence of metabolic derangements, such as diabetes and obesity. Other
      aspects of sexual function, as evaluated by IIEF subdomains, were also improved
      with TTh including libido, intercourse satisfaction, orgasm, and overall sexual
      satisfaction. CONCLUSIONS: TTh significantly improves erectile function and other
      sexual parameters as measured by IIEF in hypogonadal men. These results argue
      that sexual dysfunction should be considered a hallmark manifestation of T
      deficiency, since those symptoms can be significantly improved with normalization
      of serum T. In addition, these results suggest that TTh alone may be considered a
      reasonable treatment for hypogonadal men with milder degrees of erectile
      dysfunction, whereas the addition of other treatments, such as phosphodiesterase
      type 5 inhibitors, may be more appropriate for men with more severe erectile
      dysfunction. PATIENT SUMMARY: We investigated the effect of testosterone
      treatment on sexual function by performing a meta-analysis of all available
      studies that used the most frequently used assessment tool, the International
      Index of Erectile Function. We found that testosterone treatment significantly
      improves erectile dysfunction, as well as other aspects of sexual function, in
      men with testosterone deficiency. This treatment may be all that is required for
      hypogonadal men with milder erectile dysfunction; however, additional treatments
      may be necessary in more severe cases.

PMID- 28434677
TI  - The Microbiome of the Prostate Tumor Microenvironment.
AB  - BACKGROUND: The advent of molecular-based methods of identification and
      characterization of complex microbial populations has led to a new era of
      microbial discovery. A detailed and comprehensive analysis of the microbial
      ecosystem of the pathologic and healthy prostate tissues has not been yet
      reported. OBJECTIVES: To characterize the microbiome possibly associated to the
      pathologic prostate microenvironment. DESIGN, SETTING, AND PARTICIPANTS: The
      microbiome profile of tumor, peri-tumor, and nontumor tissues was assessed on 16
      radical prostatectomy-specimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Microbiome analysis was assessed by massive ultradeep pyrosequencing. Bacteria
      load was expressed as a percentage of the total number of bacteria. The
      statistical significance of differences among specimen-groups was tested with
      Friedman's test (Dunn posthoc test) and Wilcoxon rank-sum test. RESULTS AND
      LIMITATIONS: Three phyla, six classes, nine orders, 14 families, and 11 genera
      were above the set threshold value of 1%, respectively. Significant differences
      in specific microbial populations among tumor/peri-tumor and nontumor prostate
      specimens were observed at certain taxonomic levels. Among genera,
      Propionibacterium spp. were the most abundant. Staphylococcus spp. were more
      represented in the tumor/peri-tumor tissues (p<0.05). The restricted number of
      specimens represents a potential limitation. CONCLUSIONS: The prostate contains a
      plethora of bacteria, which set themselves within the gland with a distribution
      dependent on the nature of the tissue, thus suggesting a possible
      pathophysiological correlation between the composition of the local microbial
      niche and the presence of the tumor itself. Future studies will help to clarify
      the role of these specific bacteria and their potential to be exploited as new
      biomarkers. PATIENT SUMMARY: The pathological prostate is populated by specific
      microbial populations, whose distribution varies according to the nature of the
      tissue. This finding opens interesting perspectives for the identification of
      novel therapeutic approaches and biomarkers.

PMID- 28434678
TI  - Do not let the Spanish "s" misguide you.
AB  - The orthographic representation of the "s" in the Spanish language may have three
      phonetic variations and be associated with other phonological phenomena that add
      to its unpredictability when used to evaluate the closest speaking space. These
      are of clinical interest since each of these variations may represent a more or
      less pronounced difference from what is observed in the English language and
      patient population. The present article explains the previously mentioned
      variations and reviews the suggested Spanish terms for evaluation of the closest
      speaking space.

PMID- 28434679
TI  - Effect of fabrication stages and cementation on the marginal fit of CAD-CAM
      monolithic zirconia crowns.
AB  - STATEMENT OF PROBLEM: Monolithic zirconia crowns fabricated using computer-aided
      design and computer-aided manufacturing (CAD-CAM) technology have recently become
      an alternative dental prosthetic treatment. The marginal fit of monolithic
      zirconia crown may be affected by different stages of the fabrication procedures
      in the laboratory and cementation. Information regarding the accuracy of fit of
      monolithic zirconia crowns at different stages of fabrication and cementation is
      limited. PURPOSE: The purpose of this in vitro study was to evaluate the effect
      of different stages of fabrication and cementation on the vertical marginal
      discrepancy (VMD) of CAD-CAM fabricated monolithic zirconia crowns. MATERIAL AND
      METHODS: Six ivorine right maxillary first molar typodont teeth with standardized
      anatomic preparations for complete coverage ceramic crowns were scanned with a 3
      dimensional laboratory scanner. Crowns were designed using CAD software and
      milled from presintered monolithic zirconia blocks in a 5-axis dental milling
      machine. A cement space of 25 MUm for the margins and a 50-MUm space starting 1
      mm above the finish lines of the teeth were virtually set in the CAD software. A
      total of 144 measurements were performed on 6 specimens with 8 measurement
      locations in 3 different stages using stereoscopic zoom microscopy; after initial
      production of the crowns (post-sintering group), after glazing (post-glazing
      group), and after cementation (post-cementation group). The VMD values were
      statistically analyzed with 1-way repeated measures ANOVA and the Holm-Sidak
      method (alpha=.05). RESULTS: Different stages of fabrication and cementation
      significantly affected the VMD of tested crowns (P=.003). The mean VMD was 38 MUm
      for post-sintering group, 38 MUm for post-glazing group, and 60 MUm for post
      cementation group, with statistical differences between the post-sintering group,
      the post-cementation group (P<.002), and the post-glazing group and post
      cementation group (P<.003); there were no statistical differences between the
      post-sintering group and the post-glazing group (P=.966). CONCLUSIONS: Within the
      limitations of this in vitro study, glazing did not significantly change the VMD
      of CAD-CAM monolithic zirconia crowns. Cementation significantly increased the
      VMD values.

PMID- 28434680
TI  - Inhibition of denture plaque by TiO2 coating on denture base resins in the mouth.
AB  - STATEMENT OF PROBLEM: Information is lacking about antiadhesion effect of
      titanium dioxide (TiO2) coating on denture base resins in the mouth. PURPOSE: The
      purpose of this clinical study was to investigate the antiadhesion effect of TiO2
      coating on denture base resins. MATERIAL AND METHODS: Ten healthy dentate
      participants (mean 27 +/-2 years of age) participated in this study. Disks and
      palatal appliances were made with denture base resin. They were divided into 2
      groups: a TiO2-coated group and an uncoated group. A primer and a top coat
      containing TiO2 were applied to the surfaces of the resin by means of an air
      spray. In the denture plaque staining test, resin disks were fixed to the
      retainer, placed in each participant's mouth for 3 days, and stained with a
      dental plaque-disclosing solution. The staining rate was calculated. The resin
      disks and palatal appliances were used to measure the total number of microbes.
      The resin specimens were placed in each participant's mouth for either 3 or 7
      days and swabbed to count the total number of microbes. The chewing gum adherence
      test was performed both subjectively and objectively. Subjectively, each
      participant wearing a palatal appliance rated adherence using a visual analog
      scale. The objective test was performed with a chewing gum adhesion test. The
      staining rate, the total number of microbes, and the visual analog scale values
      were statistically analyzed using the Wilcoxon signed rank test, and the adhesive
      force was statistically analyzed using a Student t test. RESULTS: In the denture
      plaque staining test, the measurement of microbes, and the resin chewing gum
      adherence test results, significant differences were observed between the TiO2
      coated groups and the uncoated groups. CONCLUSIONS: TiO2 coating of the denture
      base acrylic resin inhibited the adhesion of microbes, denture plaque, and highly
      adhesive food.

PMID- 28434681
TI  - The use of monolithic lithium disilicate for posterior screw-retained implant
      crowns.
AB  - Lithium disilicate is typically used for fabricating prosthetic crowns to be
      cemented on teeth or implant abutments. However, its use for producing screw
      retained implant crowns has been less commonly described. This report describes
      the use of monolithic lithium disilicate for a screw-retained implant crowns.

PMID- 28434682
TI  - A proposed linear skeletal distance to predict occlusal vertical dimension: A
      cephalometric study.
AB  - STATEMENT OF PROBLEM: Establishing a correct occlusal vertical dimension is
      considered one of the most important aspects of facial esthetics for patients in
      need of oral rehabilitation. PURPOSE: The purpose of this retrospective study was
      to evaluate the use of a proposed linear skeletal distance to predict the
      appropriate occlusal vertical dimension. MATERIAL AND METHODS: A total of 93
      digital cephalometric radiographs were collected in Joint Photographic Experts
      Group (JPEG) format (51 men, 42 women) from the archive of the orthodontics
      department at the Faculty of Dentistry, Sana'a University, Yemen. The distance
      from nasion (Na) to sella (Se) and the distance from anterior nasal spine (ANS)
      to menton (Me) were measured on the cephalometric radiographs, using ImageJ
      software. The data were compared statistically using the Pearson correlation
      coefficient, regression analysis, and paired- and 1-sample t tests (alpha=.05).
      RESULTS: The findings of the study revealed a significant positive correlation
      (P<.001) between the measured distances in men, with minimum difference between
      the variables. However, no significant correlation (P=.058) was found for women.
      CONCLUSIONS: The distance from Na to Se can be used as an additional aid in
      estimating the occlusal vertical dimension in men for the study population.

PMID- 28434683
TI  - A method of fabricating an accurate repositioning device for relocating multiple
      multiunit abutments.

PMID- 28434684
TI  - Surgical safety checklist for dental implant and related surgeries.

PMID- 28434685
TI  - Influence of inhomogeneous dental posts on stress distribution in tooth root and
      interfaces: Three-dimensional finite element analysis.
AB  - STATEMENT OF PROBLEM: In post-and-core crown restorations, the use of flexible
      posts concentrates stresses at the dentin and the use of stiff posts concentrates
      stresses at the interfaces. A class of inhomogeneous materials (called
      functionally graded materials) has been proposed for posts to resolve the
      weaknesses of both flexible and rigid posts. PURPOSE: The purpose of this in
      vitro study was to design an inhomogeneous post and investigate its influence on
      the stress distribution of post-and-core crown restorations. MATERIAL AND
      METHODS: An extracted tooth was mounted, sectioned, and photographed to create a
      3-dimensional model of the first premolar tooth. The post-and-core crown
      restoration was modeled with and without a ferrule. The surrounding tissues of
      the mandibular tooth, periodontal ligament, and cortical and trabecular bones
      were modeled. Fiber-reinforced composite (FRC), metallic, and inhomogeneous posts
      were investigated by finite element analysis and the stress distribution results
      compared. RESULTS: FRC posts resulted in the highest maximum tensile stress (MTS)
      at the remaining dentin (90.4 to 93.2 MPa), while inhomogeneous posts graded by
      index n=10 (FGM10) caused the lowest MTS, both with and without a ferrule (72.3
      to 74.8 MPa). CONCLUSIONS: The use of FRC posts concentrated more MTS at the
      dentin and less MTS at the dentin-adhesive interface than metallic posts.
      Inhomogeneous posts (FGM10) resolved the weaknesses of both flexible and rigid
      posts by simultaneously reducing stresses at the dentin and interface. The
      ferrule effect resulted in fewer dentin and interface stresses.

PMID- 28434686
TI  - Effects of trimethylsilane plasma coating on the hydrophobicity of denture base
      resin and adhesion of Candida albicans on resin surfaces.
AB  - STATEMENT OF PROBLEM: Candida-associated denture stomatitis is the most common
      oral mucosal lesion among denture wearers. Trimethylsilane (TMS) plasma coating
      may inhibit the growth of Candida albicans on denture surfaces. PURPOSE: The
      purpose of this in vitro study was to investigate whether TMS plasma coatings can
      effectively reduce C albicans adhesion on denture base acrylic resin surfaces.
      MATERIAL AND METHODS: Sixty denture base acrylic resin disks with smooth and
      rough surfaces were prepared and were either left untreated (control group) or
      coated with TMS monomer (experimental group) by using plasma. Contact angles were
      measured immediately after TMS plasma coating. The morphology of C albicans
      adhesion was observed with scanning electron microscopy (SEM). Energy-dispersive
      spectroscopy (EDS) was used to characterize the elemental composition of the
      specimen surface. An adhesion test was performed by incubating the resin disk
      specimens in C albicans suspensions (1*107 cells/mL) at 37 degrees C for 24 hours
      and further measuring the optical density of the C albicans by using a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay test. One-way
      ANOVA and 2-way ANOVA were followed by a post hoc test analysis (alpha=.05).
      RESULTS: The group with TMS coating exhibited a more hydrophobic surface than the
      control group. EDS analysis revealed successful TMS plasma coating. The
      difference in the mean contact angles between the uncoated group and the TMS
      coated group was statistically significant (P<.05), 79.0 +/-2.9 degrees versus
      105.7 +/-1.5 degrees for the smooth surface and 90.2 +/-7.6 degrees versus 131.5
      +/-2.1 degrees for the rough surface. In SEM analysis, the C albicans biofilm was
      found to grow more on the surface of the denture base resin without the TMS
      coating than on the surfaces of the experimental group. In the adhesion test, the
      amount of C albicans adhering to the surface of denture base resin with the TMS
      coating was significantly less than that on the surfaces without TMS coating
      (P<.05). CONCLUSIONS: TMS coating significantly reduced the adhesion of C
      albicans to the denture base resin and may reduce denture stomatitis.

PMID- 28434687
TI  - Vaccine hesitancy among parents in a multi-ethnic country, Malaysia.
AB  - BACKGROUND: Vaccine hesitancy is a threat in combating vaccine-preventable
      diseases. It has been studied extensively in the Western countries but not so
      among Asian countries. OBJECTIVES: To assess the test-retest reliability of the
      Parent Attitudes about Childhood Vaccines (PACV) questionnaire in Malay language;
      to determine the prevalence of vaccine hesitancy among parents and its
      associations with parents' socio-demographic characteristics. METHODS: Forward
      and backward translation of PACV in Malay language was carried out. The
      reliability of the Malay-PACV questionnaire was tested among parents with
      children. The same questionnaire was used to study vaccine hesitancy among
      parents in a tertiary hospital in Kuala Lumpur. Information pertaining to socio
      demographic characteristics, sources of information regarding vaccination and
      vaccine hesitancy were collected. Associations between vaccine hesitancy with
      socio-demographic factors were tested using Multivariable Logistic Regression.
      RESULTS: The Spearman correlation coefficient and Cronbach alpha for total PACV
      was 0.79 (p<0.001) and 0.79 respectively. The intra-class correlation
      coefficients of the subscales ranged from 0.54 to 0.90 demonstrating fair to
      excellent reliability. A total of 63 (11.6%) parents were noted to be vaccine
      hesitant. In the univariate analyses, vaccine hesitancy was associated with
      unemployed parents, parents who were younger, had fewer children and non-Muslim.
      In the multivariate model, pregnant mothers expecting their first child were four
      times more likely to be vaccine hesitant compared to those who already had one or
      more children (aOR: 3.91, 95% CI: 1.74-8.79) and unemployed parents were also
      more likely to be vaccine hesitant (aOR: 1.97, 95% CI: 1.08-3.59). The internet
      (65.6%) was the main source of information on vaccination followed by brochures
      (56.9%). CONCLUSION: The Malay-PACV questionnaire is reliable to be used. The
      prevalence of vaccine hesitancy among the multi-ethnic Malaysians was comparable
      with other populations. Pregnant mothers expecting their first child and
      unemployed parents were found to be more vaccine hesitant.

PMID- 28434688
TI  - Stability of heat stable, live attenuated Rotavirus vaccine (ROTASIIL(r)).
AB  - Vaccines currently available across the globe are stored and transported in a
      continuous cold-chain at 2-8 degrees C or below -20 degrees C. A temperature
      excursion outside this range affects the potency of the vaccines. Such vaccines
      need to be discarded leading wastage. The Rotavirus disease burden is
      predominantly reported in developing and low-income countries and therefore, has
      entered or poised to enter their national immunization programs. These countries
      already have several limitations for effective storage, maintenance and
      distribution of vaccines in a cold-chain and this introduction is expected to
      further stress this fragile ecosystem. To help mitigate the cold chain related
      issues, SIIPL has developed a thermostable rotavirus vaccine ROTASIIL(r) which
      can be stored at a temperature below 25 degrees C for 36months, completely by
      passing the standard 2-8 degrees C cold storages. In addition it has the
      capability to withstand temperatures of 37 degrees C and 40 degrees C for
      18months and short term exposure to 55 degrees C. It can also tolerate a
      temperature shock of being thawed from an extreme cold temperature of -20 degrees
      C to a high temperature of 42 degrees C. The vaccine contains serotypes G1, G2,
      G3, G4 and G9 (UK-Bovine reassortant strains procured from National Institute of
      Health-USA). The vaccine is recently licensed in India.

PMID- 28434689
TI  - Early childhood transmission of hepatitis B prior to the first hepatitis B
      vaccine dose is rare among babies born to HIV-infected and non-HIV infected
      mothers in Gulu, Uganda.
AB  - BACKGROUND: Hepatitis B (HBV) in sub-Saharan Africa is believed to be
      horizontally acquired. However, because of the high HBV prevalence in northern
      Uganda, no hepatitis B vaccination at birth and no access to HBV immunoglobulin,
      we hypothesize that vertical transmission also could also play an important role.
      We therefore investigated the incidence of HBV among babies presenting for their
      first HBV vaccine dose in Gulu, Uganda. METHODS: We recruited mothers and their
      babies (at least 6-week old) presenting for their postnatal care and first HBV
      vaccine dose respectively. Socio-demographic and risk factors for HBV
      transmission were recorded. Mothers were tested for Hepatitis B core antibody
      (anti-HBc-IgG) and hepatitis B surface antigen (HBsAg). HBsAg-positive sera were
      tested for hepatitis B e antigen (HBeAg) and HBV viral load (HBVDNA). Babies were
      tested for HBsAg at presentation and at the last immunization visit. A sample of
      HBsAg-negative babies were tested for HBVDNA. Incident HBV infection was defined
      by either a positive HBsAg or HBVDNA test. Chi-square or fisher's exact tests
      were utilized to investigate associations and t-tests or Wilcoxon rank-sum test
      for continuous differences. RESULTS: We recruited 612 mothers, median age 23years
      (IQR 20-28). 53 (8.7%) were HBsAg-positive and 339 (61.5%) were anti-HBc-IgG
      positive. Ten (18.9%) of the HBsAg-positive mothers were HBeAg-positive. Median
      HBVDNA levels of HBV-infected mothers was 5.7log (IQR 4.6-7.0) IU/mL with 9
      (17.6%) having levels>=105IU/mL. Eighty (13.3%) mothers were HIV-infected of whom
      9 (11.5%) were co-infected with HBV. No baby tested HBsAg or HBVDNA positive.
      CONCLUSION: Vertical transmission does not seem to contribute substantially to
      the high HBV endemicity in northern Uganda. The current practice of administering
      the first HBV vaccine to babies in Uganda at six weeks of age may be adequate in
      control of HBV transmission.

PMID- 28434690
TI  - Assessment of potential miRNA biomarkers of VERO-cell tumorigenicity in a new
      line (AGMK1-9T7) of African green monkey kidney cells.
AB  - Patterns of microRNA expression appear to delineate the process of spontaneous
      neoplastic development-transformation (SPNDT) occurring in the African green
      monkey kidney (AGMK) VERO cell line (Teferedegne et al., 2010). Analysis of
      microarray data identified 6 microRNAs whose high-level of expression peaked when
      the World Health Organization 10-87 VERO cells became tumorigenic at passage (p)
      190. Six miRNAs were identified as potential biomarkers for the expression of the
      VERO-cell tumorigenic phenotype (Teferedegne et al., 2014). However, the question
      remained whether these miRNA biomarkers are specific for VERO cells or can be
      generalizable to other cells originating from African green monkey kidneys. To
      examine miRNA expression patterns in AGMK cells at lower passage levels and to re
      examine the identified miRNAs as biomarkers associated with tumorigenic phenotype
      of VERO cells in another independently-derived line, we established a new line of
      African green monkey kidney cells (AGMK1-9T7) by serially passaging kidney cells
      from another AGM. The AGMK1-9T7 cells became tumorigenic in nude mice at p40.
      Evaluation of miRNA expression at intervals from p1 to p40 revealed similarities
      between the evolution of miRNA expression during SPNDT in the AGMK1-9T7 cells and
      the 10-87 VERO cells. Four of the 6 potential biomarker miRNAs (miR-376a, miR-654
      3p, miR-543, miR-134) in our earlier reports were detected by microarray in the
      AGMK1-9T7 cells; RT-qPCR analysis detected all 6 miRNAs. All 6 of these miRNAs
      have been associated with human tumors. Detection of the same miRNAs associated
      with the tumorigenic p40 AGMK1-9T7 cells and tumorigenic 10-87 VERO cells
      confirmed our proposal that these miRNA represent biomarkers for the tumor
      forming ability of AGMK/VERO cells. The similarities of expression of miRNAs in
      different AGMK cell lines that were established 50years apart suggest that the
      process of SPNDT in these non-human primate cells in tissue culture is based upon
      similar genetic and epigenetic mechanisms.

PMID- 28434691
TI  - Immunogenicity to poliovirus type 2 following two doses of fractional intradermal
      inactivated poliovirus vaccine: A novel dose sparing immunization schedule.
AB  - INTRODUCTION: The polio eradication endgame strategic plan calls for the
      sequential removal of Sabin poliovirus serotypes from the trivalent oral
      poliovirus vaccine (tOPV), starting with type 2, and the introduction of >=1 dose
      of inactivated poliovirus vaccine (IPV), to maintain an immunity base against
      poliovirus type 2. The global removal of oral poliovirus type 2 was successfully
      implemented in May 2016. However, IPV supply constraints has prevented
      introduction in 21 countries and led to complete stock-out in >20 countries.
      METHODS: We conducted a literature review and contacted corresponding authors of
      recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose
      administered intradermally, to conduct additional type 2 immunogenicity analyses
      of two fIPV doses compared with one full-dose IPV. RESULTS: Four studies were
      identified that assessed immunogenicity of two fIPV doses compared to one full
      dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2
      seroconversion rates improving between absolute 19-42% (median: 37%, p<0.001) and
      relative increase of 53-125% (median: 82%), and antibody titer to type 2
      increasing by 2-32-fold (median: 10-fold). Early age of administration and
      shorter intervals between doses were associated with lower immunogenicity.
      DISCUSSION: Overall, two fIPV doses are more immunogenic than a single full-dose,
      associated with significantly increased seroconversion rates and antibody titers.
      Two fIPV doses together use two-fifth of the vaccine compared to one full-dose
      IPV. In response to the current IPV shortage, a schedule of two fIPV doses at
      ages 6 and 14weekshas been endorsed by technical oversight committees and has
      been introduced in some affected countries.

PMID- 28434693
TI  - Letter to the Editor on "Abnormally High Dislocation Rates of Total Hip
      Arthroplasty After Spinal Deformity Surgery".

PMID- 28434694
TI  - A Prospective Randomized Trial of Mini-Incision Posterior and 2-Incision Total
      Hip Arthroplasty: Minimum 5-Year Follow-Up.
AB  - BACKGROUND: We previously described the results of a randomized controlled trial
      of mini-posterior vs 2-incision total hip arthroplasty and were unable to
      demonstrate significant differences in early outcomes. As less-invasive anterior
      approaches remain popular, the purpose of this report was to re-examine the
      outcomes at a minimum 5-year follow-up. METHODS: Seventy-two patients undergoing
      primary total hip arthroplasty were randomized to a mini-posterior or 2-incision
      approach. Complications, revisions, and clinical outcome measures were compared.
      Radiographs were reviewed for implant loosening. A power analysis using a minimal
      clinically important difference value of 6 points for the Harris hip score
      revealed 28 patients required per group. RESULTS: At a mean of 8.2 years (range,
      5-10 years), 6 patients died without revision surgery and 63 of 66 living
      patients were reviewed. There were 6 total failures, 3 in each group. For
      unrevised patients, there were no significant differences between groups
      (posterior vs 2-incision) in the Harris hip score (95.5 +/- 3.5 vs 95.7 +/- 6.3;
      P = .88), 12-item Short Form Survey physical composite score (50.5 +/- 8.5 vs
      49.0 +/- 9.1; P = .53), 12-item Short Form Survey mental composite score (57.3 +/
      4.1 vs 55.4 +/- 8.0; P = .25), or single assessment numeric evaluation score
      (97.1 +/- 3.7 vs 97.8 +/- 5.2; P = .55). CONCLUSION: We found no differences in
      midterm outcomes between the 2 approaches. Given the increased complexity,
      operative time, and need for fluoroscopy with the 2-incision approach combined
      with equivalent early and midterm outcomes, the 2-incision approach has been
      abandoned in the senior author's practice.

PMID- 28434692
TI  - Immune hyperreactivity of Abeta plaque-associated microglia in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is strongly associated with microglia-induced
      neuroinflammation. Particularly, Abeta plaque-associated microglia take on an
      "activated" morphology. However, the function and phenotype of these Abeta plaque
      associated microglia are not well understood. We show hyperreactivity of Abeta
      plaque-associated microglia upon systemic inflammation in transgenic AD mouse
      models (i.e., 5XFAD and APP23). Gene expression profiling of Abeta plaque
      associated microglia (major histocompatibility complex II+ microglia) isolated
      from 5XFAD mice revealed a proinflammatory phenotype. The upregulated genes
      involved in the biological processes (gene ontology terms) included: "immune
      response to external stimulus" such as Axl, Cd63, Egr2, and Lgals3, "cell
      motility", such as Ccl3, Ccl4, Cxcr4, and Sdc3, "cell differentiation", and
      "system development", such as St14, Trpm1, and Spp1. In human AD tissue with
      similar Braak stages, expression of phagocytic markers and AD-associated genes,
      including HLA-DRA, APOE, AXL, TREM2, and TYROBP, was higher in laser-captured
      early-onset AD (EOAD) plaques than in late-onset AD plaques. Interestingly, the
      nonplaque parenchyma of both EOAD and late-onset AD brains, the expression of
      above-mentioned markers were similarly low. Here, we provide evidence that Abeta
      plaque-associated microglia are hyperreactive in their immune response and
      phagocytosis in the transgenic AD mice as well as in EOAD brain tissue. We
      suggest that Abeta plaque-associated microglia are the primary source of
      neuroinflammation related to AD pathology.

PMID- 28434695
TI  - The Influence of a Failed Irrigation and Debridement on the Outcomes of a
      Subsequent 2-Stage Revision Knee Arthroplasty.
AB  - BACKGROUND: Previous work has suggested a failed irrigation and debridement (I&D)
      before a 2-stage exchange negatively impacts the outcome of the subsequent 2
      stage revision. METHODS: This was a retrospective review of 132 patients who
      underwent a 2-stage exchange without prior I&D (2-Stage), and 45 patients had a
      failed I&D before their 2-stage exchange (I&D+2Stage) between April 2009 and
      April 2015. Charts were reviewed for patient demographics, presenting
      inflammatory laboratory values, type of antibiotic spacer used, surgical details,
      microbiology data, length of postoperative antibiotic treatment, and reoperation.
      A logistic regression was used to assess the association between I&D and
      reoperation. RESULTS: The I&D+2Stage group had an 82.2% success rate, and the 2
      Stage group had an 82.5% success rate (P = .95). The odds of reoperation for
      infection with the use of greater than 2 grams of vancomycin was 0.33 (P = .01,
      95% confidence interval 0.14-0.79) as compared with having less than 2 grams of
      vancomycin in the construct. Spacer type, having a prior I&D to the 2-stage
      procedure, being infected with an antibiotic resistant organism, total grams of
      aminoglycoside were not associated with a risk of failure. CONCLUSION: Success
      rates between the I&D+2Stage group and the 2-Stage group were similar. The use of
      greater than 2 grams of vancomycin in the spacer construct decreased the odds of
      reoperation. I&D before a 2-stage exchange may not negatively influence the
      outcomes of a subsequent 2-stage revision procedure and requires further
      investigation.

PMID- 28434696
TI  - Complete Eradication of Biofilm From Orthopedic Materials.
AB  - BACKGROUND: Interest exists in finding alternatives to current management
      strategies in periprosthetic joint infections, which typically include a 2-stage
      revision with placement of an antibiotic spacer and delayed placement of a new
      implant. We studied the efficacy of autoclaving, ultrasonication, and mechanical
      scrubbing for sterilization and biofilm eradication on infected cobalt-chrome
      discs. METHODS: Strains of Staphylococcus aureus MRSA252 or Staphylococcus
      epidermidis RP62A were grown on the discs. For each strain, discs were divided
      into 5 groups (5 discs each) and exposed to several sterilization and biofilm
      eradication treatments: (1) autoclave, (2) autoclave + sonication, (3) autoclave
      + saline scrub, (4) autoclave + 4% chlorhexidine (CHC) scrub, and (5) autoclave +
      sonication + CHC scrub. Sterilization and biofilm eradication were quantified
      with crystal violet assays and scanning electron microscopy. RESULTS: Relative to
      nontreated controls, autoclaving alone reduced biofilm load by 33.9% and 54.7%
      for MRSA252 and RP62A strains, respectively. Biofilm removal was maximized with
      the combined treatment of autoclaving and CHC scrub for MRSA252 (100%) and RP62A
      (99.5%). The addition of sonication between autoclaving and CHC scrubbing
      resulted in no statistically significant improvement in biofilm removal. High
      resolution scanning electron microscopy revealed no cells or biofilm for this
      combined treatment. CONCLUSION: Using 2 commonly encountered bacterial strains in
      periprosthetic joint infection, infected cobalt-chrome discs were sterilized and
      eradicated of residual biofilm with a combination of autoclaving and CHC
      scrubbing.

PMID- 28434697
TI  - Poor Outcomes of Irrigation and Debridement in Acute Periprosthetic Joint
      Infection With Antibiotic-Impregnated Calcium Sulfate Beads.
AB  - BACKGROUND: One proposed strategy to increase the success of irrigation and
      debridement with implant retention for the treatment of acute periprosthetic
      joint infection (PJI) is the use of dissolvable antibiotic-impregnated calcium
      sulfate beads to provide a local depot of antibiotics. The purpose of this study
      was to evaluate the outcome of such an approach. METHODS: Thirty-two patients
      with acute hematogenous (18 patients; 1 bilateral) or acute postoperative (14
      patients) PJIs who underwent irrigation and debridement with implant retention
      and addition of antibiotic-impregnated calcium sulfate beads were retrospectively
      reviewed. PJI followed 27 total knee arthroplasties and 6 total hip
      arthroplasties. The most common infecting organisms were methicillin-sensitive
      Staphylococcus aureus (13 of 33) and Streptococcus (9 of 33). The primary outcome
      parameter was recurrence of infection according to the Musculoskeletal Infection
      Society criteria. Patients were followed up for a minimum of 3 months or until
      failure. RESULTS: At a mean of 12.7 months (range, 3-30 months), 16 of the 33
      patients failed (48%). Acute hematogenous and acute postoperative PJI had similar
      failure rates at 47% and 50%, respectively (P = .88). Seven failures required a 2
      stage exchange, while 8 patients were treated with chronic antibiotic
      suppression, being unwilling or unable to undergo further surgical intervention.
      CONCLUSION: The addition of antibiotic-impregnated calcium sulfate beads does not
      appear to improve outcomes of irrigation and debridement with implant retention
      in the setting of acute hematogenous or acute postoperative PJI. Given the short
      follow-up in this report, this represents a best-case scenario and the overall
      failure rate may be higher with further follow-up.

PMID- 28434698
TI  - Influence of Component Rotation in Total Knee Arthroplasty on Tibiofemoral
      Kinematics-A Cadaveric Investigation.
AB  - BACKGROUND: Physiological tibiofemoral kinematics have been shown to be important
      for good knee function after total knee arthroplasty (TKA). The purpose of the
      present study was to investigate the influence of component rotation on
      tibiofemoral kinematics during knee flexion. We asked which axial component
      alignment best reconstructs physiological tibiofemoral kinematics and which
      combinations should be avoided. METHODS: Ten healthy cadaveric knees were
      examined. By means of a navigational device, tibiofemoral kinematics between 0
      degrees  and 90 degrees  of flexion were assessed before and after TKA using the
      following different rotational component alignment: femoral components: ligament
      balanced, 6 degrees  internal, 3 degrees  external rotation, and 6 degrees 
      external rotation in relation to the posterior condylar line; tibial components:
      self-adapted, 6 degrees  internal rotation, and 6 degrees  external rotation.
      RESULTS: Physiological tibiofemoral kinematics could be partly reconstructed by
      TKA. Ligament-balanced femoral rotation and 6 degrees  femoral external rotation
      both in combination with 6 degrees  tibial component external rotation, and 3
      degrees  femoral external rotation in combination with 6 degrees  tibial
      component internal rotation or self-aligning tibial component were able to
      restore tibial longitudinal rotation. Largest kinematical differences were found
      for the combination femoral component internal and tibial component external
      rotations. CONCLUSION: From a kinematic-based view, surgeons should avoid
      internal rotation of femoral components. However, even often recommended
      combinations of rotational component alignment (3 degrees  femoral external and
      tibial external rotation) significantly change tibiofemoral kinematics. Self
      aligning tibial components solely restored tibiofemoral kinematics with the
      combination of 3 degrees  femoral component of external rotation. For the future,
      navigational devices might help to axially align components to restore patient
      specific and natural tibiofemoral kinematics.

PMID- 28434699
TI  - Reproducibility and Precision of CT Scans to Evaluate Tibial Component Rotation.
AB  - BACKGROUND: Component rotation likely plays a greater role on the survivorship
      and outcomes of total knee arthroplasties than is currently known. Our goal was
      to evaluate the precision, interobserver reliability, and intrarater reliability
      of tibial component rotation as measured by computed tomography (CT) scan,
      regardless of measurement technique. METHODS: Three fellowship-trained, academic
      arthroplasty surgeons independently measured tibial component rotation on CT
      scans of 62 total knee arthroplasties using their methods of choice. Measurements
      were repeated at least 2 weeks after the initial measurement. The precision of
      the measurements was assessed using a formal 8-step protocol as the gold
      standard. Intraclass correlation coefficients (ICCs) were calculated to evaluate
      precision, interobserver agreement, and intrarater reliability RESULTS: The
      interobserver agreement between the 3 surgeons for tibial component rotation was
      also moderate (ICC = 0.52). The intrarater reliability of tibial rotation was
      excellent (ICC = 0.81). Comparison of surgeons' measurement to a validated gold
      standard revealed only moderate precision for tibial component rotation (ICC =
      0.64). CONCLUSION: Practicing surgeons measuring tibial rotation were internally
      consistent, but failed to demonstrate satisfactory precision and interobserver
      agreement. We support the adoption of standardized criteria for the measurement
      of tibial component rotation on CT scans.

PMID- 28434700
TI  - Incidence, etiology, and management of type III endoleak after endovascular
      aortic repair.
AB  - OBJECTIVE: The objective of this study was to retrospectively assess the
      incidence, etiology, and management of type III endoleaks in a large cohort of
      patients treated with endovascular aneurysm repair (EVAR) in two European
      university centers. METHODS: From 1995 until 2014, 965 EVAR procedures were
      performed with use of first- and second-generation (n = 79) or third-generation
      (n = 886) endografts. Radiologic follow-up was performed with computed tomography
      and abdominal plain film examinations in accordance with the European
      Collaborators on Stent/graft Techniques for aortic Aneurysm Repair (EUROSTAR)
      scheme. The potential relationship between the type of endograft and the
      incidence of type III endoleak and the time interval between initial EVAR and
      diagnosis of type III endoleak were calculated. RESULTS: Twenty patients (2.1%)
      were identified with 25 type III endoleaks (n = 10/79 [12.7%] for first- and
      second-generation endografts and n = 10/886 [1.2%] for third-generation
      endografts; P < .001). Disconnection was found in 14 of 25 endoleaks (56%) and a
      fabric defect in 11 of 25 (44%) endoleaks, both without any difference between
      first- and second- vs third-generation endografts (P = .216). The time interval
      between initial EVAR and type III endoleak was 3.87 and 5.92 years, respectively,
      for first- or second-generation and third-generation endografts (P = .148).
      Twenty-five type III endoleaks were treated using endovascular techniques (n = 22
      [88%]) or by open surgical conversion (n = 3 [12%]). CONCLUSIONS: Type III
      endoleak rarely (2.1%) occurs after EVAR, with a higher incidence in first- and
      second-generation endografts. In the majority of cases, the underlying mechanism
      is disconnection of the stent graft components. Type III endoleaks may occur
      early or late after initial EVAR and can, in most cases, be managed
      endovascularly, although type III endoleak may recur.

PMID- 28434701
TI  - Upregulated interleukins (IL-6, IL-10, and IL-13) in immunoglobulin G4-related
      aortic aneurysm patients.
AB  - OBJECTIVE: Immunoglobulin (Ig) G4-related aortic aneurysms (IgG4-AAs) are a
      special aortic aneurysm among IgG4-related diseases (IgG4-RDs), which are
      inflammatory and fibrous conditions characterized by tumorous swelling of
      affected organs and high serum IgG4 concentrations. Recently, IgG4-RD
      pathogenesis was shown to be associated with T-helper-2 (Th2) and regulatory T
      (Treg) dominant cytokine production, such as interleukin (IL)-4, IL-10, and IL
      13. IL-6 is a key proinflammatory cytokine contributing to lymphocyte and
      plasmacyte maturation and to atherosclerosis and aneurysm development. We
      serologically and histopathologically evaluated the cytokine profile in IgG4-AA
      patients. METHODS: Patients with IgG4-AAs (n = 10), non-IgG4-related inflammatory
      abdominal aortic aneurysms (non-IgG4-AAAs; n = 5), atherosclerotic AAAs (aAAAs; n
      = 10), and normal aortas without dilatation (n = 10) were examined for serum IL
      10, IL-13, and IL-6 levels. Resected aortic tissues were evaluated for cluster of
      differentiation (CD) 34 (in the endothelial cells and mesenchymal cells) and
      CD163 (by macrophages) expression using immunohistochemistry and in situ
      hybridization. RESULTS: Serum IL-10 levels were rather higher in IgG4-AA patients
      (median, 1.3 pg/mL) than in non-IgG4-AAA and aAAA patients and in patients with
      normal aortas. Elevated serum IL-13 levels relative to standard values were
      detected in two IgG4-AA patients but not in the other groups. Cells
      immunopositive for IL-10 and IL-13 were more frequent in IgG4-AAs and
      significantly correlated with serum IgG4 levels. Serum IL-6 levels (median, 78.5
      pg/mL) were also significantly higher in IgG4-AA patients than in non-IgG4-AAA
      and aAAA patients and control patients with normal aortas (P = .01, P = .001, and
      P = .004, respectively). They positively correlated with serum IgG4 levels and
      adventitial thickness, but other cytokines did not. The number of IL-6
      immunopositive cells in the adventitia was significantly higher in IgG4-AA
      patients (median, 17.8/high-power field) than in aAAA patients or patients with
      normal aortas (P =.001 and P = .002, respectively). In situ hybridization
      confirmed frequent IL-6 messenger (m)RNA expression in the endothelium,
      mesenchymal cells, and histiocytes in IgG4-AA adventitia. In the same cells of
      IgG4-AAs, coexpression of IL-6 and CD34 mRNA or CD163 mRNA was detected.
      CONCLUSIONS: The cytokine profiles of IgG4-AA patients had two characteristics:
      local IL-10 and IL-13 upregulation in IgG4-AAs was related to Th2 and Treg
      predominant cytokine balance, similar to other IgG4-RDs, and IL-6 upregulation in
      the adventitia was characterized by activated immune reactions in IgG4-AA
      patients. IL-6 synthesis, through contributions of mesenchymal cells and
      macrophages in the adventitia, is strongly involved in IgG4-AA pathogenesis or
      progression, or both.

PMID- 28434703
TI  - Glomerular filtration rate estimation in people older than 85: Comparison between
      CKD-EPI, MDRD-IDMS and BIS1 equations.
AB  - BACKGROUND: The evidence of glomerular filtration rate (GFR) estimating with
      serum creatinine based formulae in the elderly population is scarce. The purpose
      of this study is to compare CKD-EPI, MRD4-IDMS and BIS1 equations to analyse
      correlation and concordance in a population older than 85 years old. PATIENTS AND
      METHODS: We designed a retrospective cross-sectional study, which included data
      from 600 patients older than 85 years. GFR was estimated by the following
      equations: CKD-EPI, MDR4-IDMS and BIS1, using as variables sex, age and serum
      creatinine concentration. Statistics analysis included Wilcoxon test, Bland
      Altman plot, non-parametric Passing-Bablok method and kappa statistic (simple and
      weighted). RESULTS: The patients' median (range) age was 87 (interval 85-98). The
      median GFR (range) was 42.4 (5.2-127.4) mL/min/1.73 m2, when it was estimated
      with MDRD-IDMS, 40.0 (4.5-93.1) for CKD-EPI and 36.9 (7.6-83.7) for BIS1. The
      comparison of BIS1 and CKD-EPI and MDRD-IDMS using the Wilcoxon test was
      significant (P<.001). The regression analysis yielded the following equations:
      MDRD-IDMS= 1,025*CKD-EPI+1.360; BIS1= 0.688*CKD-EPI+9.074 and BIS1= 0.666*MDRD
      IDMS+8.401. The weighted coefficient was 0.958 for the concordance between MDRD
      IDMS and CKD-EPI, 0.812 for the concordance between MDRD-IDMS and BIS1 and 0.846
      for CKD-EPI and BIS1. CONCLUSIONS: The GFR estimations obtained with BS1 equation
      are not interchangeable with MDRD-IDMS or CKD-EPI equations. BIS1 estimates lower
      GFR values than MDRD-IDMS and CKD-EPI and tends to classify the patients in a
      more advanced chronic kidney disease stage, especially for estimated GFR higher
      than 29mL/min/1.73 m2.

PMID- 28434702
TI  - Inhibition or deletion of angiotensin II type 1 receptor suppresses elastase
      induced experimental abdominal aortic aneurysms.
AB  - OBJECTIVE: Angiotensin (Ang) II type 1 receptor (AT1) activation is essential for
      the development of exogenous Ang II-induced abdominal aortic aneurysms (AAAs) in
      hyperlipidemic animals. Experimental data derived from this modeling system,
      however, provide limited insight into the role of endogenous Ang II in aneurysm
      pathogenesis. Consequently, the potential translational value of AT1 inhibition
      in clinical AAA disease management remains incompletely understood on the basis
      of the existing literature. METHODS: AAAs were created in wild-type (WT) and AT1a
      knockout (KO) mice by intra-aortic infusion of porcine pancreatic elastase (PPE).
      WT mice were treated with the AT1 receptor antagonist telmisartan, 10 mg/kg/d in
      chow, or the peroxisome proliferator-activated receptor gamma (PPARgamma)
      antagonist GW9662, 3 mg/kg/d through oral gavage, beginning 1 week before or 3
      days after PPE infusion. Influences on aneurysm progression as well as
      mechanistic insights into AT1-mediated pathogenic processes were determined using
      noninvasive ultrasound imaging, histopathology, aortic gene expression profiling,
      and flow cytometric analysis. RESULTS: After PPE infusion, aortic enlargement was
      almost completely abrogated in AT1a KO mice compared with WT mice. As defined by
      a >=50% increase in aortic diameter, no PPE-infused, AT1a KO mouse actually
      developed an AAA. On histologic evaluation, medial smooth muscle cellularity and
      elastic lamellae were preserved in AT1a KO mice compared with WT mice, with
      marked attenuation of mural angiogenesis and leukocyte infiltration. In WT mice,
      telmisartan administration effectively suppressed aneurysm pathogenesis after PPE
      infusion as well, regardless of whether treatment was initiated before or after
      aneurysm creation or continued for a limited or extended time. Telmisartan
      treatment was associated with reduced messenger RNA levels for CCL5 and matrix
      metalloproteinases 2 and 9 in aneurysmal aortae, with no apparent effect on
      PPARgamma-regulated gene expression. Administration of the PPARgamma antagonist
      GW9662 failed to "rescue" the aneurysm phenotype in telmisartan-treated, PPE
      infused WT mice. Neither effector T-cell differentiation nor regulatory T-cell
      cellularity was affected by telmisartan treatment status. CONCLUSIONS:
      Telmisartan effectively suppresses the progression of elastase-induced AAAs
      without apparent effect on PPARgamma activation or T-cell differentiation. These
      findings reinforce the critical importance of endogenous AT1 activation in
      experimental AAA pathogenesis and reinforce the translational potential of AT1
      inhibition in medical aneurysm disease management.

PMID- 28434704
TI  - Establishment of buttonhole technique as a puncture alternative for arteriovenous
      fistulas. experience of a centre over 3years.
AB  - INTRODUCTION: The buttonhole (BH) puncture technique for arteriovenous fistulas
      is an alternative to the classical staggered puncture. PURPOSE: We present
      3years' results incorporating the BH puncture technique for arteriovenous
      fistulas in our dialysis unit. MATERIAL AND METHODS: Twenty-two patients were
      started on BH technique, 15 men and 7 women (mean age: 62 years; SD: 12), with
      time spent on dialysis when starting the BH technique of 34 months (SD: 34,
      median: 27, range: 3-136). Seven patients received acenocoumarol and 9
      antiplatelet agents. The vascular access median time at the beginning of the
      technique was 27 months (range: 3-252). RESULTS: Between 5 and 8 consecutive
      dialysis sessions were necessary to achieve a proper tunnel puncture. No patient
      suffered major complications. The average time on BH technique until December
      2015 was 12 months (SD: 10, median: 9, range: 1-45). By the end of the study,
      5patients were performing self-puncture. Haemostasis times post-dialysis were
      reduced from 18.6min (SD: 8, prior to the BH technique), to 12.2minutes (SD: 3
      after BH) (P=.0005). CONCLUSIONS: The BH technique is an alternative puncture
      technique for dialysis patients. Self-puncture and reduction in hemostasis time
      are potential beneficial aspects. A greater diffusion of this technique in the
      hemodialysis units would allow it to be better applied. A highly motivated
      nursing staff is key and a necessary condition for its implementation.

PMID- 28434705
TI  - Protein-losing enteropathy in a patient on peritoneal dialysis.

PMID- 28434706
TI  - Role of kidney MRI to monitoring clearance of hemosiderin deposits in paroxysmal
      nocturnal hemoglobinuria.

PMID- 28434707
TI  - In-hospital complications after implantation of cardiac implantable electronic
      devices: Analysis of a national inpatient database in Japan.
AB  - BACKGROUND: Complications after implantation of cardiac implantable electronic
      devices (CIEDs), including permanent pacemakers (PMs) and other CIEDs, are
      associated with increased patient mortality and healthcare costs. This study
      aimed to investigate overall complications after implantation of CIEDs, analyze
      the associated risk factors, and compare complications after PM implantation
      between hospitals that performed only PM implantations (PM-only hospitals) and
      hospitals that implanted other CIEDs, as well as PMs (all-CIED hospitals).
      METHODS: Using the Japanese Diagnosis Procedure Combination database, we
      retrospectively collected data on inpatients who underwent CIED implantation from
      1 July 2010 to 31 March 2014. RESULTS: A total of 77,324 patients were
      identified, including 64,951 patients with PMs and 12,373 with other CIEDs. The
      overall incidences of in-hospital complications were 2.5% in patients with PMs
      and 2.1% in those with other CIEDs. The incidences of pocket infections, pocket
      problems, device- and lead-related problems, and sepsis were 0.9%, 0.5%, 0.4%,
      and 0.3%, respectively. The crude proportion of complications after PM
      implantation was higher in the PM-only hospitals than in the all-CIED hospitals
      (3.1% vs. 2.1%), but the multivariable logistic regression analysis showed no
      significant difference (odds ratio, 1.29; 95% confidence interval, 0.99-1.68).
      CONCLUSION: After adjusting for patient backgrounds, the occurrence of
      complications after PM implantation was not significantly different between
      patients in PM-only hospitals and those in all-CIED hospitals.

PMID- 28434709
TI  - Target analysis of tert-butyldimethylsilyl derivatives of nerve agent hydrolysis
      products by selectable one-dimensional or two-dimensional gas chromatography-mass
      spectrometry.
AB  - A target analysis method for the sensitive and discriminative determination of
      the nerve agent hydrolysis products alkyl methylphosphonic acids as their tert
      butyldimethylsilyl (TBDMS) derivatives was developed using a combination of
      selectable one- and two-dimensional (1D/2D) GC-MS, and applied to the analysis of
      samples with significant interfering matrices. After sample drying, the
      alkylmethylphosphonic acids and methylphosphonic acid (MPA) were converted to
      TBDMS derivatives by addition of N-methyl-N-(tert
      butyldimethylsilyl)trifluoroacetamide with heating, and subjected to 1D/2D GC-MS.
      The apparatus consisted of an initial low thermal mass DB-5 column and a second
      DB-17 column together with an electron ionization quadrupole mass spectrometer,
      offering simple and flexible switching between one- and two-dimensional GC-MS
      analysis in a single GC-MS system. Using 1D/2D GC-MS, analytes that do not co
      elute with matrix components can be separated using 1D GC mode alone. Only those
      parts of the chromatogram that are negatively affected by the co-elution of
      matrix components need to be transferred and separated with 2D GC. Quantitation
      can be performed by a combination of both separations and mass spectrometric
      detection. The TBDMS derivatives of ethyl-, isopropyl-, isobutyl-, pinacolyl-,
      and cyclohexyl-MPA (cHMPA) and MPA itself were well separated within 3min and
      determined in 1D GC-MS mode with detection limits of around 10ng/ml of reaction
      mixture (except for the cHMPA derivative, whose mass spectrum contained noisy
      background peaks). In 2D-GC-MS mode, where each 0.04min elution window from the
      1D GC was subjected to heart-cut (H/C) and transferred to the second column after
      back-flushing the first column, the peak for the cHMPA TBDMS derivative was
      isolated and afforded a clean mass spectrum within 6min. The recoveries of all
      the derivatives on 2D GC from 1D GC were estimated to be over 66%, and the
      detection limits were around 10ng/ml of reaction mixture. In the presence of
      urine extract, the target compounds were not detected as separated peaks in 1D GC
      MS mode (except for isobutyl-MPA), and quantification based on extracted ion
      monitoring could not be achieved. However, 2D GC-MS of the H/C fractions of the
      target derivatives gave single peaks with well-defined mass spectra, and the
      recoveries of the derivatives were over 70% except for cHMPA (31% at 1.25MUg/ml).
      Phosphonic acids could be detected at less than 60ng/ml. Sulfuric acid and
      phosphoric acid also negatively affected the determination of alkyl
      methylphosphonic acid TBDMS derivatives in 1D GC-MS, and the MPA-TBDMS-derivative
      peak was completely obscured by the large sulfuric-acid-derivative peak. However,
      under 1D/2D GC-MS conditions, baseline separation of the MPA derivative and
      sulfuric acid derivative was achieved, enabling highly sensitive MPA detection at
      20ng/ml.

PMID- 28434708
TI  - Dual-phase 18F-florbetapir positron emission tomography in patients with primary
      progressive aphasia, Alzheimer's disease, and healthy controls: A preliminary
      study.
AB  - BACKGROUND/PURPOSE: To determine whether dual-phase 18F-florbetapir positron
      emission tomography imaging with perfusion-like and amyloid deposition
      information can distinguish among primary progressive aphasia (PPA), Alzheimer's
      disease (AD), and healthy controls (HCs). METHODS: Patients diagnosed with PPA,
      including four semantic dementia (SD) and two progressive nonfluent aphasia
      (PNFA), as well as one logopenic variant (LV) of PPA, were studied. All PPA
      patients, and age-/sex-matched patients with probable AD (n=8) and HCs (n=8) were
      subjected to dual-phase 18F-florbetapir imaging. Atlas-based quantitative volumes
      of interest (VOIs) analysis for six cortical areas and whole cerebellum was
      performed. The standardized uptake value ratios were calculated by normalizing
      the dual-phase-integrated activities of the six VOIs to whole cerebellum counts.
      RESULTS: Early phase 18F-florbetapir image showed significantly lower global
      perfusion index in six PPA patients as compared with HCs. According to VOI
      analysis, the hypoperfusion lesions were identified in the frontal, anterior
      cingulate, parietal, precuneus, and temporal regions. Similar findings were
      confirmed by voxel-base image comparison. 18F-florbetapir late-phase image showed
      significantly increased amyloid burden in the global cortex index and all six
      brain regions of eight AD and LV patients when compared with the other six PPA
      patients and eight HCs. There was no apparent uptake of amyloid tracer in both
      six PPA patients and eight HCs. CONCLUSION: Dual-phase 18F-florbetapir images of
      six PPA (SD and PNFA) patients showed hypoperfusion in the frontotemporal cortex,
      and little global amyloid uptake, which may be a distinct image pattern for
      differentiation among HC, AD, and PPA patients.

PMID- 28434710
TI  - Shifting the paradigm in gas chromatography mass spectrometry pesticide analysis
      using high resolution accurate mass spectrometry.
AB  - In the last 10 years, the majority of the pesticide food control laboratories
      moved from GC-MS to GC-MS/MS as the preferred analytical technique to address GC
      amenable compounds. The main reason for this change was the negative impact on
      the single stage GC-MS analysis caused by the interference from coeluting matrix
      compounds. The new development of gas chromatography coupled to high resolution
      accurate mass spectrometry (GC-HRAMS) provides opportunities to overcome such
      matrix interferences as a result of its much higher selectivity; allowing
      laboratories to carry out full-scan analysis covering the most exigent analytical
      performance criteria. The aim of this work is the evaluation of the main
      analytical performance parameters for the multiresidue screening of pesticide
      residues by a gas chromatography-OrbitrapTM mass spectrometer in fruits and
      vegetables. Electron ionization and full-scan high resolution mass spectrometry
      was selected for this evaluation. Mass resolving power, selectivity, sensitivity,
      analyte identification and database generation are discussed in light of the
      analysis of various commodities and a large scope of pesticides. The selected
      operational conditions provided optimal mass accuracy, within +/-1mDa and
      achieved LOQs of 10MUg/kg or lower for practically all the selected pesticides
      and commodities. Applicability for quantitative residue analysis was verified by
      the validation of the 210 pesticides in four matrices (tomato, apple, leek and
      orange). The performance of the GC-EI-full scan Orbitrap HRAMS developed method
      was confirmed with the analysis of 102 real samples providing good results.

PMID- 28434711
TI  - Validation of an ultra-high-performance liquid chromatography-tandem mass
      spectrometry method to quantify illicit drug and pharmaceutical residues in
      wastewater using accuracy profile approach.
AB  - The analysis of biomarkers in wastewater has become a common approach to assess
      community behavior. This method is an interesting way to estimate illicit drug
      consumption in a given population: by using a back calculation method, it is
      therefore possible to quantify the amount of a specific drug used in a community
      and to assess the consumption variation at different times and locations. Such a
      method needs reliable analytical data since the determination of a concentration
      in the ngL-1 range in a complex matrix is difficult and not easily reproducible.
      The best analytical method is liquid chromatography - mass spectrometry coupling
      after solid-phase extraction or on-line pre-concentration. Quality criteria are
      not specially defined for this kind of determination. In this context, it was
      decided to develop an UHPLC-MS/MS method to analyze 10 illicit drugs and
      pharmaceuticals in wastewater treatment plant influent or effluent using a pre
      concentration on-line system. A validation process was then carried out using the
      accuracy profile concept as an innovative tool to estimate the probability of
      getting prospective results within specified acceptance limits. Influent and
      effluent samples were spiked with known amounts of the 10 compounds and analyzed
      three times a day for three days in order to estimate intra-day and inter-day
      variations. The matrix effect was estimated for each compound. The developed
      method can provide at least 80% of results within +/-25% limits except for
      compounds that are degraded in influent.

PMID- 28434712
TI  - Evidence for an imidazoline by-product from glycans using tandem mass
      spectrometry.
AB  - Herein is reported the separation and identification of a previously unknown
      imidazoline by-product originating from the fluorescent labeling procedure when
      applied to enzymatically released N-linked glycans of a human IgG1. The
      imidazoline by-product was generated via the reductive amination procedure with
      either sodium cyanoborohydride or 2-picoline borane. Using ultra performance
      liquid chromatography (UPLC) in conjunction with hydrophilic interaction-based
      chromatography (HILIC), the 2-aminobenzoic acid (2-AA)-labeled glycans were well
      resolved from imidazoline by-products to facilitate direct identification
      utilizing electrospray ionization mass spectrometry (ESI-MS) with fragmentation.
      It was found that this minor species (~2%) was 18.0105u less than the neighboring
      peak GlcNAc2Man3GlcNAc2Fuc peak, abbreviated as A2G0F at 1582.5899u. While this
      mass loss corresponds to the mass of a water molecule, the molecular location of
      loss of water was not straightforward in consideration of the biantennary A2G0F
      structure. Model studies were carried out using A2G0F standard and N
      acetyllactosamine to identify the impurity as an imidazoline ring structure
      located at the reducing end of the glycan as confirmed by high resolution mass
      fragment ions. Imidazoline content decreased when the reductant concentration was
      increased. To conclude, evidence for the imidazoline structure was accomplished
      through high resolution, high accuracy mass spectrometry (HRAM), and experiments
      showing chemical susceptibility and isotopically labeled tracers. This study is
      the first to identify these minor species which likely impact all N
      acetylglucosamine-type N-linked glycans from biologics.

PMID- 28434713
TI  - Detection of trace fluoride in serum and urine by online membrane-based
      distillation coupled with ion chromatography.
AB  - An online membrane-based distillation (MBD) coupled with ion chromatography (IC)
      method was proposed for automatic detection of trace fluoride (F-) in serum and
      urine samples. The system consisted of a sample vessel, a lab-made membrane
      module and an ion chromatograph. Hydrophobic polytetrafluoroethylene (PTFE)
      hollow fiber membrane was used in MBD which was directly performed in serum and
      urine samples to eliminate the matrix interferences and enrich fluoride, while
      enabling automation. The determination of fluoride in biological samples was
      carried out by IC with suppressed conductometric detection. The proposed method
      feasibly determined trace fluoride in serum and urine matrices with the optimized
      parameters, such as acid concentration, distillation temperature, and
      distillation time, etc. Fluoride exhibited satisfactory linearity in the range of
      0.01-5.0mg/L with a correlation coefficient of 0.9992. The limit of detection
      (LOD, S/N=3) and limit of quantification (LOQ, S/N=10) were 0.78MUg/L and
      2.61MUg/L, respectively. The relative standard deviations of peak area and peak
      height were all less than 5.15%. The developed method was validated for the
      determination of fluoride in serum and urine with good spiked recoveries ranging
      between 97.1-101.9%. This method also can be proposed as a suitable alternative
      for the analysis of fluoride in other complex biological samples.

PMID- 28434714
TI  - Speed-resolution advantage of turbulent supercritical fluid chromatography in
      open tubular columns: II - Theoretical and experimental evidences.
AB  - The potential advantage of turbulent supercritical fluid chromatography (TSFC) in
      open tubular columns (OTC) was evaluated on both theoretical and practical
      viewpoints. First, the dispersion model derived by Golay in 1958 and recently
      extended from laminar to turbulent flow regime is used for the predictions of the
      speed-resolution performance in TSFC. The average dispersion coefficient of
      matter in the turbulent flow regime was taken from the available experimental
      data over a range of Reynolds number from 2000 to 6000. Kinetic plots are built
      at constant pressure drop (DeltaP=4500psi) and Schmidt number (Sc=15) for four
      inner diameters (10, 30, 100, and 300MUm) of the OTC and for three retention
      factors (0, 1, and 10). Accordingly, in turbulent flow regime, for a Reynolds
      number of 4000 and a retention factor of 1 (the stationary film thickness is
      assumed to be negligible with respect to the OTC diameter), the theory projects
      that a 300MUm i.d. OTC has the same speed-resolution power (200,000 theoretical
      plates; 2.4min hold-up time) as that of a 10MUm i.d. OTC operated in laminar flow
      regime. Secondly, the experimental plate heights of n-butylbenzene are measured
      in laminar and turbulent flow regimes for a 180MUm*4.8m fused silica capillary
      column using pure carbon dioxide as the mobile phase. The back pressure regulator
      was set at 1500psi, the temperature was uniform at 297K, and the flow rate was
      increased step-wise from 0.50 to 3.60mL/min so that the experimental Reynolds
      number increases from 700 to 5400. The experiments are in good agreement with the
      plate heights projected in TSFC at high flow rates and with those expected at low
      flow rates in a laminar flow regime.

PMID- 28434715
TI  - Separation of Janus droplets and oil droplets in microchannels by wall-induced
      dielectrophoresis.
AB  - The continuous separation of different types of droplets from a mixture is
      important in industrial and research applications. Currently researches for
      droplet separation focus on homogeneous emulsion droplets, and there is no study
      on the separation of heterogeneous droplets. The wall-induced dielectrophoresis,
      which originates from the non-uniform electrical field around a sphere nearby a
      planar wall, can be applied to separate dielectric particle and cells. In this
      work, the continuous separations of oil droplets and the electrically induced
      Janus droplets (EIJDs) in a microchannel by using the wall-induced
      dielectrophoresis method were presented. The wall-induced dielectrophoretic
      lateral migration of a droplet depends on the size and surface charge of the
      droplet. In this study, the wall-induced dielectrophoretic lateral migrations of
      oil droplets and Janus droplets in a straight microchannel under different
      strengths of electrical fields were investigated first, and the experimental
      results match well with the theoretical predictions. Then, the separations of oil
      droplets by size, separations of Janus droplets by size, and separation of
      mixtures of Janus droplets and oil droplets with the same size were conducted,
      respectively. The experimental results demonstrate that, with this method, the
      separations of target oil droplets or Janus droplets with specific size can be
      accomplished by simply adjusting the voltages applied to the microchannel.

PMID- 28434716
TI  - A bioinformatics analysis of 3400 lytic polysaccharide oxidases from family AA9.
AB  - Lytic polysaccharide monooxygenases of family AA9 catalyze the oxidative cleavage
      of glycosidic bonds in cellulose and related polysaccharides. The N-terminal half
      of AA9 LPMOs displays a huge sequence variability that is in contradiction with
      the substrate simplicity so far observed for these enzymes. To understand the
      cause of the high multigenicity that prevails in the family, we have performed a
      clustering analysis of the N-terminal region of 3400 sequences of family AA9
      LPMOs, and have evaluated the coincidence of the clusters with distal visible
      features that may accompany functional differences. A method based on local
      pairwise alignments was devised to avoid the pitfalls of a global multiple
      alignment. Our analysis allowed the definition of 64 clusters, which successfully
      segregated several visible features associated to LPMO family AA9, such as the
      presence of carbohydrate-binding modules, of modules of unknown function and of
      the conspicuous H -> R substitution at the first residue of the histidine brace
      that holds the catalytic copper. Our analysis shows that the hypervariability of
      the N-terminal half of the AA9 sequences is not driven by random evolution as
      sequence similarity does not follow solely taxonomy. The results suggest that
      some clusters are perhaps able to target chitin instead of cellulose, and that
      preference for C1 or C4 oxidation (or lack thereof), does not appear to
      constitute a strong evolutionary constraint. On an evolutionary standpoint, there
      seems to be little constraints that apply to the N-terminal half of the sequences
      other than the conservation of the histidine brace. The weak evolutionary
      constraints that apply to the N-terminal half of AA9 LPMOs explain both their
      hypervariability and multigenicity.

PMID- 28434717
TI  - Relative Genetic and Environmental Contributions to Variations in Human Retinal
      Electrical Responses Quantified in a Twin Study.
AB  - PURPOSE: To estimate heritability of parameters of human retinal
      electrophysiology and to explore which parameters change with age. DESIGN:
      Prospective, classic twin study. PARTICIPANTS: Adult monozygotic and dizygotic
      twin pairs recruited from the TwinsUK cohort. METHODS: Electroretinogram
      responses were recorded using conductive fiber electrodes in response to stimuli
      incorporating standards set by the International Society for the Clinical
      Electrophysiology of Vision. These parameters were extracted; in addition,
      photopic negative-response (PhNR; originating from retinal ganglion cells) and i
      wave components were extracted from responses to the photopic single flash.
      Parameter values were averaged from both eyes. MAIN OUTCOME MEASURES: Mean values
      were calculated for the cohort. Correlation coefficients with age were calculated
      (averaging parameters from both twins from each pair). Coefficients of intrapair
      correlation were calculated for monozygotic and dizygotic twins. Age-adjusted
      heritability estimates were derived using standard maximum likelihood structural
      equation twin modeling. RESULTS: Responses were recorded from 210 participants in
      total (59 monozygotic and 46 dizygotic twin pairs). Ninety-three percent were
      women. Mean age for the cohort was 62.4 years (standard deviation, 11.4 years).
      In general, response amplitudes correlated negatively, and implicit times
      positively, with age. Correlations were statistically significant (P < 0.05) and
      moderate or strong (coefficient, >0.35) for the following parameters: scotopic
      standard and bright-flash a-wave implicit times, photopic 30-Hz flicker and
      single-flash b-wave implicit times, and PhNR and i-wave implicit times. Intrapair
      correlations were higher for monozygotic than dizygotic twins, suggesting
      important genetic influences. Age-adjusted estimates of heritability were
      significant for all parameters (except scotopic dim-flash b-wave implicit time),
      ranging from 0.34 to 0.85. Highest estimates were for photopic single-flash a
      wave and b-wave amplitudes (0.84 and 0.85, respectively). CONCLUSIONS: This study
      explored heritability of retinal electrophysiologic parameters and included
      measurements reflecting ganglion cell function. Most parameters showed
      significant heritability, indicating that genetic factors are important,
      determining up to 85% of the variance in some cone system response parameters.
      Scotopic responses tended to show lower heritability (possibly relating to
      greater rod system susceptibility to environmental factors). Future studies can
      explore the identity of these genetic factors, improving our understanding of how
      they shape retinal function.

PMID- 28434718
TI  - Corrigendum to "Extracting Low-Velocity Concentric and Eccentric Dynamic Muscle
      Properties from Isometric Contraction Experiments" Mathematical Biosciences 278
      (2016) 77-93.
AB  - We provide corrections to our paper "Extracting Low-Velocity Concentric and
      Eccentric Dynamic Muscle Properties from Isometric Contraction Experiments,
      Mathematical Biosciences 278 (2016), p. 77-93", where we used an erroneous form
      of Hatze's activation dynamics. The statements of the paper still hold true in
      general, even though the numerical values of Tables 1, 2, and 3 slightly vary.
      The authors would like to apologize for any inconvenience caused.

PMID- 28434719
TI  - Pituitary volume reduction in schizophrenia following cognitive behavioural
      therapy.
AB  - Cognitive behavioural therapy (CBT) for psychosis (CBTp) aims to lower the stress
      of psychotic symptoms. Given that the pituitary is involved in stress regulation,
      CBT-led stress reduction may be accompanied by a change in pituitary volume. This
      study aimed to determine whether CBTp reduces pituitary volume in schizophrenia.
      The relation between pre-therapy memory and CBTp-led pituitary volume change was
      also examined given that poor memory relates to a blunted cortisol awakening
      response, denoting impaired stress response, in schizophrenia. Pituitary volume
      was measured at baseline in 40 schizophrenia or schizoaffective disorder patients
      and 30 healthy participants before therapy. Pituitary volume was measured again 6
      9months after patients had either received CBTp in addition to standard care
      (CBTp+SC, n=24), or continued with standard care alone (SC, n=16). CBTp+SC and SC
      groups were compared on pituitary volume change from baseline to follow-up. Pre
      therapy memory performance (Hopkins Verbal Learning and Wechsler Memory Scale -
      Logical memory) was correlated with baseline-to-follow-up pituitary volume
      change. Pituitary volume reduced over time in CBTp+SC patients. Additionally, pre
      therapy verbal learning correlated more strongly with longitudinal pituitary
      volume reduction in the CBTp+SC group than the SC group. To conclude, CBTp
      reduces pituitary volume in schizophrenia most likely by enhancing stress
      regulation and lowering the distress due to psychotic symptoms.

PMID- 28434720
TI  - Short- and longer-term effects of feeding increased metabolizable protein with or
      without an altered amino acid profile to dairy cows immediately postpartum.
AB  - The first few weeks after parturition is marked by low, but increasing feed
      intake and sharply increasing milk production by dairy cows. Because of low
      intake, the nutrient density of the diet may need to be higher during this period
      to support increasing milk yields. We hypothesized that feeding higher levels of
      metabolizable protein (MP) or a protein supplement with rumen-protected lysine
      and methionine during the immediate postpartum period would increase yields of
      milk and milk components. Fifty-six Holstein cows (21 primiparous and 35
      multiparous) starting at 3 d in milk were used in a randomized block design. In
      phase 1 (3 through 23 d in milk), cows were fed 1 of 3 diets that differed in
      supply of MP and AA profile. At 23 d in milk, all cows were moved to a common
      freestall pen and fed the control diet used in phase 1 for an additional 63 d
      (phase 2). Diets were formulated using the National Research Council model and
      were control [16.5% crude protein (CP), 10.9% rumen-degradable protein (RDP), and
      5.6% rumen-undegradable protein (RUP)], high MP (HMP; 18.5% CP, 11.6% RDP, 6.9%
      RUP), and AA (MPAA; 17.5% CP, 10.5% RDP, 7.0% RUP 29.7). The MPAA diet included a
      proprietary spray-dried blood meal product (Perdue Agribusiness, Salisbury, MD)
      and contained a model-estimated 7.2 and 2.6% of digestible lysine and methionine
      (% of MP). The HMP and control diets contained 6.3 and 6.7% digestible lysine and
      both had 1.8% digestible methionine. In phase 1, diet did not affect milk yield
      (33.6, 34.7, and 33.2 kg for control, HMP, and MPAA, respectively), dry matter
      intake (17.8, 18.0, and 18.5 kg/d for control, HMP, and MPAA), or milk protein
      yield (1.07 kg/d). Feeding additional protein (HMP or MPAA) increased both the
      concentration and yield of milk fat, and milk protein concentration was greater
      (3.30 vs. 3.17%) for MPAA compared with the HMP diet. Energy-corrected milk was
      greater (38.4 and 38.6 vs. 35.3 kg/d, respectively) for MPAA and HP than for the
      control. Cows fed MPAA had the greatest plasma concentrations of Met and the
      lowest concentrations of isoleucine, but lysine was not affected by treatment.
      Feeding additional MP (HMP or MPAA) reduced the concentrations of 3
      methylhistidine in plasma, indicating reduced muscle breakdown. Diet effects on
      milk composition continued after cows were changed to a common diet in that cows
      fed MPAA the first 3 wk of lactation had greater concentration of milk protein
      for the entire experiment than cows fed HMP, and cows fed additional MP (HMP and
      MPAA) during phase 1 had greater concentrations of milk fat for the entire
      experiment. Increasing dietary protein and AA supply in early lactation had short
      term effects on yield of energy-corrected milk and long-term effects on milk
      composition.

PMID- 28434721
TI  - Characterization of probiotic bacteria involved in fermented milk processing
      enriched with folic acid.
AB  - Yogurt products fermented with probiotic bacteria are a consumer trend and a
      challenge for functional food development. So far, limited research has focused
      on the behavior of the various probiotic strains used in milk fermentation. In
      the present study, we characterized folic acid production and the sensory and
      textural characteristics of yogurt products fermented with probiotic bacteria.
      Yogurt fermented with Lactobacillus plantarum had improved nutrient content and
      sensory and textural characteristics, but the presence of L. plantarum
      significantly impaired the growth and survival of Lactobacillus delbrueckii ssp.
      bulgaricus during refrigerated storage. Overall, L. plantarum was a good
      candidate for probiotic yogurt fermentation; further studies are needed to
      understand the major metabolite path of lactic acid bacteria in complex
      fermentation.

PMID- 28434722
TI  - Prediction of milk fatty acid content with mid-infrared spectroscopy in Canadian
      dairy cattle using differently distributed model development sets.
AB  - The fatty acid profile of milk is a prevailing issue due to the potential
      negative or positive effects of different fatty acids to human health and
      nutrition. Mid-infrared spectroscopy can be used to obtain predictions of
      otherwise costly fatty acid phenotypes in a widespread and rapid manner. The
      objective of this study was to evaluate the prediction of fatty acid content for
      the Canadian dairy cattle population from mid-infrared spectral data and to
      compare the results produced by altering the partial least squares (PLS) model
      development set used. The PLS model development sets used to develop the
      predictions were reference fatty acids expressed as (1) grams per 100 g of fatty
      acid, (2) grams per 100 g of milk, (3) the natural logarithmic transform of grams
      per 100 g of milk, and (4) subsets of samples randomly selected by removing
      excess records around the mean to present a more uniform distribution, repeated
      10 times. Gas chromatography measured fatty acid concentration and spectral data
      for 2,023 milk samples of 373 cows from 4 breeds and 44 herds were used in the
      model development. The coefficient of determination of cross-validation (Rcv2)
      increased when fatty acids were expressed on a per 100 g of milk basis compared
      with on a per 100 g of fat basis for all examined fatty acids. The logarithmic
      transformation used to create a more Gaussian distribution in the development set
      had little effect on the prediction accuracy. The individual fatty acids C12:0,
      C14:0, C16:0, C18:0, C18:1n-9 cis, and saturated, monounsaturated, unsaturated,
      short-chain, medium-chain, and long-chain fatty acid groups had (Rcv2) greater
      than 0.70. When model development was performed with subsets of the original
      samples, slight increases in (Rcv2) values were observed for the majority of
      fatty acids. The difference in (Rcv2) between the top- and bottom-performing
      prediction equation across the different subsets for a single predicted fatty
      acid was on average 0.055 depending on which samples were randomly selected to be
      used in the PLS model development set. Predictions for fatty acids with high
      accuracies can be used to monitor fatty acid contents for cows in milk recording
      programs and possibly for genetic evaluation.

PMID- 28434723
TI  - Labeling strategies to overcome the problem of niche markets for sustainable milk
      products: The example of pasture-raised milk.
AB  - Pasture-raised milk is gaining in importance in some European countries and in
      the United States. The production of pasture-raised milk is linked to higher
      costs, as the milk is normally collected and processed separately from
      conventional barn milk. This could hinder the production of sustainable milk
      products. We discuss alternative labeling strategies that allow the mixing of
      pasture-raised (sustainable) and conventional milk to reduce costs and break free
      from the current niche market. The lower price would allow for more pasture
      raised milk to be produced and enter the mainstream market. The aim of this study
      was to analyze consumers' willingness to pay for alternative labeling types using
      a discrete choice experiment with 1,065 German milk buyers. The 2 alternative
      labels, besides the classical labeling approach, are based on the mass balance
      approach (at least 50% pasture-raised milk in a package) and cause-related
      marketing (support of farmers who keep their cows on pasture). The discrete
      choice experiment was combined with a cluster analysis to get a deeper
      understanding of the buying behavior of the diverse consumer segments for milk.
      We found that all consumer groups prefer the classical label where products are
      segregated but also understand the benefits of cause-related marketing. The
      average consumer was willing to pay ?0.50 more for pasture-raised milk certified
      with the classical label and ?0.38 more for pasture-raised milk labeled with a
      cause-related marketing claim. However, differences between the clusters are
      strong: The smallest cluster of ethically involved consumers (15%) is willing to
      pay the highest premiums, especially for the classical label. Cause-related
      marketing is an interesting alternative for involved buyers under price pressure
      (41%), whereas the mass balance approach is little understood and thus less
      valued by consumers. From our results we concluded that cause-related marketing
      (in our case, the support of pasturing of dairy cows) can be useful for dairies
      for which it is not efficient to collect and process products separately. This
      approach is furthermore suitable for reaching consumers who are mainly interested
      in altruistic issues but at the same time are more price sensitive, as this
      labeling strategy does not need separate collection and processing and can
      thereby be marketed at a lower price.

PMID- 28434724
TI  - The effect of presynchronization with prostaglandin F2alpha and gonadotropin
      releasing hormone simultaneously, 7 d before Ovsynch, compared with Presynch
      10/Ovsynch on luteal function and first-service pregnancies per artificial
      insemination.
AB  - Pregnancy per artificial insemination (P/AI) following Ovsynch is optimized when
      cows ovulate to the first GnRH of Ovsynch. Fertility programs are designed to
      presynchronize cows to d 6 or 7 of the estrous cycle to increase the chances of
      ovulation of a first-wave dominant follicle to the first GnRH of Ovsynch. The
      hypothesis of this experiment was that simplification of a presynchronization
      program through the combination of PGF2alpha and GnRH on the same day, 7 d before
      Ovsynch, would allow for similar P/AI compared with Presynch-10. Lactating dairy
      cows (n = 432) 41 to 47 d in milk (DIM) were randomly assigned to 2 treatments
      within parities for first service. Control cows received Presynch-10/Ovsynch
      consisting of the following: PGF2alpha-14 d-PGF2alpha-10 d-GnRH-7 d-PGF2alpha-56
      h-GnRH-16 h-AI. Treated cows received PGF2alpha and GnRH-7 d-GnRH-7 d-PGF2alpha
      56 h-GnRH-16 h-AI. All cows received a supplemental injection of PGF2alpha 24 h
      after the PGF2alpha of Ovsynch to enhance complete luteolysis. All cows received
      timed AI between 75 and 81 DIM. Blood was collected to assess circulating
      concentrations of progesterone (P4), and the number and size of corpora lutea
      (CL) were recorded using ultrasonography on day of PGF2alpha of Ovsynch. The
      administration of PGF2alpha simultaneously with GnRH and 7 d before Ovsynch
      (PG+G) had similar P/AI at 28 (46 vs. 48%), 35 (43 vs. 43%), 49 (39 vs. 39%), and
      77 d post-AI (38 vs. 39%) compared with Presynch-10. No differences were observed
      in P/AI in primiparous versus multiparous cows at 28 (52 vs. 45%), 35 (48 vs.
      41%), 49 (45 vs. 37%), and 77 d post-AI (43 vs. 36%). No difference existed
      between treatments in percentage of cows with functional CL at PGF2alpha of
      Ovsynch, total luteal area (mm2), or serum concentrations of P4 at time of
      PGF2alpha of Ovsynch, regardless of parity. Number of CL had a tendency to be
      greater for multiparous PG+G vs. Presynch-10 cows (2.34 +/- 0.09 vs. 2.15 +/-
      0.08) but not in primiparous cows (1.95 +/- 0.10 vs. 1.98 +/- 0.11). In summary,
      administering both PGF2alpha and GnRH on the same day, 7 d before the start of
      Ovsynch, appears to be a simple and effective alternative to Presynch-10 Ovsynch.

PMID- 28434725
TI  - Effects of breed, feeding system, and lactation stage on milk fat characteristics
      and spontaneous lipolysis in dairy cows.
AB  - Spontaneous lipolysis (SL) is an enzymatic reaction that leads to a release of
      fatty acids that can modify technological and sensory properties of milk and milk
      products. However, few studies have been done to assess the effect of feeding
      systems (FS) and breed on SL. Most of them were conducted in the 1980s and are
      not fully representative of cattle today. No previous study investigated the
      effect of cow breed at the whole-lactation scale. Thus, a trial was carried out
      to study the effects of 2 FS (high- and low-input FS) with 2 breeds [Holstein
      (HO) and Normande (NO)] during 1 entire lactation. Sixty-three cows were followed
      throughout 1 lactation. Cows were divided into 4 groups according to their breed
      and their FS. The high FS (HFS) consisted of a high-energy diet (in winter, corn
      silage with 30% concentrate; otherwise, pasture with 4 kg/d of concentrate) and
      the low FS (LFS) consisted of a low-energy diet (in winter, conserved grass with
      no concentrate; otherwise, pasture with no concentrate). The cows calved between
      January and March. Individual milk samples were collected every month from both
      morning and evening milkings for fat, protein, milk fat globule size, major fatty
      acids and proteins profiles, and SL determinations. Data were analyzed using the
      mixed procedure of SAS. The SL was higher in evening milks compared with morning
      milks. In early lactation, in evening milks, SL was higher in LFS than in HFS. No
      difference was shown according to the FS in mid and late lactation. Pasture was
      associated with low SL rate in mid lactation. The NO cows were less susceptible
      to SL during the entire lactation than HO cows. Finally, early and late lactation
      periods were identified as being more susceptible to SL, but this depended on
      breed and FS. During early lactation, HO cows and LFS were associated with higher
      levels of SL, particularly in evening milks, and, during late lactation, HO cows
      were associated with higher levels of SL. No intertreatment or intercow
      correlations (coefficient of determination <0.16) were found between SL, milk fat
      and protein contents, milk production, milk fat globule size, proportion of fatty
      acids and proteins, body condition, and weight during the entire lactation.
      Effects of breed, FS, and lactation stage were clearly identified and quantified.
      Causal mechanisms might involve energy balance and circadian secretion of milk
      fat globule components.

PMID- 28434726
TI  - Short communication: Sensory analysis of a kefir product designed for active
      cancer survivors.
AB  - Kefir is a fermented milk product that is a good source of protein and health
      promoting bacteria. It has the potential to improve recovery from exercise and
      the health and well-being of cancer survivors. The purpose of this study was to
      explore cancer survivor attitudes about and acceptance of a kefir recovery
      beverage made from cultured milk, whole fruit, natural sweeteners, and other
      natural ingredients. Kefir was made by inoculating and fermenting milk with kefir
      grains. The kefir was then mixed with a fruit base and given to cancer survivors
      (n = 52) following a bout of exercise. Participants evaluated the acceptability
      of the beverage samples (overall appearance, aroma, taste, mouthfeel, and overall
      liking) using a 9-point hedonic scale, and they evaluated the smoothness using a
      3-category just-about-right scale (not enough, just about right, and too much).
      They also expressed their physical and psychological feelings about the beverage
      using a 5-point scale (1 = not at all to 5 = extremely) and indicated their
      purchase intent using a binomial (yes/no) response. The health benefits of kefir
      were then explained, and participants sampled a second beverage (the same
      product), answering the same questions related to overall liking, feeling, and
      intent to purchase. We used a paired Student's t-test to compare beverage liking
      and emotion scores before and after participants learned about the health
      benefits of kefir. Data are presented as mean +/- standard deviations. The
      beverage scored significantly higher for overall liking after the health benefits
      were explained (6.5 +/- 1.8 and 7.0 +/- 1.7 out of 9 before and after the
      explanation of health benefits, respectively). Participants showed a high intent
      to purchase before they learned about the health benefits (75% of participants
      indicated an intent to purchase, and 89% after they learned about the health
      benefits). The beverage received high scores overall and, except for an
      improvement in overall liking, we observed no significant differences in physical
      and psychological feelings before and after participants learned that it
      contained kefir and had potential health benefits. We found the beverage to be
      acceptable for consumption by cancer survivors, and the majority of participants
      showed an interest in purchasing for after exercise.

PMID- 28434727
TI  - Short-term effects of soybean oil supplementation on performance, digestion, and
      metabolism in dairy cows fed sugarcane-based diets.
AB  - We aimed to quantify the productive and metabolic responses, and digestive
      changes in dairy cows fed various concentrations of soybean oil (SBO) in high
      concentrate, sugarcane-based diets. Eight rumen-cannulated multiparous Holstein
      cows in mid lactation (574 +/- 19.1 kg of body weight and 122 +/- 6.9 d in milk),
      averaging 22.5 +/- 1.22 kg/d of milk were assigned to replicated 4 * 4 Latin
      squares. The experimental period lasted 21 d as follows: 14 d for adaptation,
      followed by a sampling period from d 15 to 21. The diets were formulated with
      increasing concentrations of SBO [% of dry matter (DM)]: control (0%), low (LSBO;
      1.57%), medium (MSBO; 4.43%), and high (HSBO; 7.34%). Dry matter intake decreased
      quadratically in response to SBO addition. The greatest decrease in DM intake was
      observed in MSBO and HSBO diets. Both milk and energy-corrected milk yield were
      quadratically affected by the SBO inclusion, with a slight decrease up to MSBO
      and substantial decrease in the HSBO diet. The milk fat concentration linearly
      decreased from 3.78% in the control to 3.50% in the HSBO diet. The potentially
      digestible neutral detergent fiber digestibility in the rumen decreased from
      55.7% in the control to 35.2% in the HSBO diet. The fractional rate of digestion
      of potentially digestible neutral detergent fiber in the rumen decreased linearly
      from 3.13 to 1.39%/h from the control to HSBO diet. The fractional rate of
      indigestible neutral detergent fiber passage in the rumen was quadratically
      affected, with the lowest value (2.25%/h) for the HSBO diet. Rumen pH increased
      from 6.42 to 6.67, and ammonia nitrogen decreased from 28.1 to 21.4 mg/dL, in the
      control and HSBO diets, respectively. Rumen volatile fatty acids decreased
      quadratically, with the greatest decrease observed in MSBO and HSBO diets. Serum
      concentrations of glucose, fatty acids, and beta-hydroxybutyrate were unaffected
      by SBO inclusion. However, serum concentrations of total cholesterol and high-
      and low-density lipoproteins linearly increased with increasing concentrations of
      SBO in the diet. Inclusion of SBO at concentrations from 4.43 to 7.34% of the
      diet DM decreased DM intake, energy-corrected milk production, fiber
      digestibility, and rumen fermentation and was thus not recommended. Soybean oil
      supplementation at 1.57% of the diet DM proved to be a safe concentration for
      dairy cows fed high-concentrate diets with sugarcane as the sole forage.

PMID- 28434728
TI  - Short communication: Parameters of abomasal emptying and glucose-insulin dynamics
      in Holstein-Friesian calves at 2 ages and 2 levels of milk replacer intake.
AB  - Elevated planes of nutrition in the preweaning period of dairy calf management
      can increase average daily gain, shorten age at puberty, and increase milk yield.
      In a previous study, 12 Holstein calves were fed 2 meals/d of 4 or 2 L milk
      replacer up to 7 wk of age. The objective of the current study was to estimate
      parameters of abomasal emptying and glucose-insulin dynamics in these calves by
      fitting a mechanistic model to postprandial appearances of plasma glucose,
      insulin, and the abomasal emptying marker acetaminophen measured at 4 and 7 wk of
      age. Higher intake of milk replacer resulted in longer bouts of abomasal emptying
      at a slower rate. Parameters of glucose and insulin dynamics were not affected by
      milk replacer intake. However, older calves had decreased insulin-stimulated
      glucose utilization indicating impaired insulin sensitivity, as well as increased
      pancreatic responsiveness. Neither of these effects were apparent from i.v.
      glucose tolerance tests on the calves and may have been related to postprandial
      gut hormone release. Effects of age on parameters of glucose-insulin dynamics
      were larger than effects of milk replacer intake. Conversely, effects of milk
      replacer intake on abomasal emptying were larger than effects of age.

PMID- 28434729
TI  - Effects of intrauterine infusion of Escherichia coli lipopolysaccharide on
      uterine mRNA gene expression and peripheral polymorphonuclear leukocytes in
      Jersey cows diagnosed with purulent vaginal discharge.
AB  - The objectives of the current experiment were to investigate the effects of
      intrauterine treatment of cows with purulent vaginal discharge (PVD) using
      lipopolysaccharide (LPS) from Escherichia coli on uterine mRNA expression of
      genes related to inflammatory responses, peripheral polymorphonuclear leukocyte
      (PMN) function, hematological parameters, and blood concentrations of cortisol,
      haptoglobin, and progesterone (P4). Jersey cows (n = 3,084) were examined for PVD
      at 35 +/- 6 d postpartum using the Metricheck device (Simcro, Hamilton, New
      Zealand). At examination, 310 cows had PVD (10.1%), but to ensure proper
      collection and processing of samples, 267 cows were used in this experiment. Cows
      were balanced for lactation number, body condition score, and milk yield, and
      randomly assigned to the control treatment [intrauterine infusion of 20 mL of
      phosphate-buffered saline (PBS); n = 87] or to receive intrauterine infusion of
      20 mL of PBS containing 150 ug (LPS150; n = 91) or 300 ug (LPS300; n = 89) of E.
      coli LPS. Uteri were biopsied in a subgroup of cows at 6 h after infusion and in
      another subgroup of cows at 24 h after infusion. Peripheral PMN expression of
      adhesion molecules (L-selectin and MAC-1) and phagocytosis and oxidative burst
      were evaluated at 0, 2, and 6 h after infusion. Blood sampled 0, 2, 6, 24, 48,
      and 168 h after infusion was used for complete hemogram and to determine
      concentrations of cortisol, haptoglobin, and P4. Treatment did not affect uterine
      mRNA expression of adhesion molecules [endothelial leukocyte adhesion molecule (E
      selectin), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion
      molecule-1 (VCAM-1)], cytokines (tumor necrosis factor-alpha, IL-1beta, IL-6, IL
      8, and IL-10), and toll-like receptor-4. Treatment did not affect PMN expression
      of L-selectin, but intensity of expression of MAC-1 was higher for LPS150 cows
      than PBS cows, and tended to be higher in LPS150 than LPS300 cows. Furthermore, a
      greater percentage of PMN from LPS300 cows were positive for phagocytosis and
      oxidative burst compared with PBS and LPS150 cows. No effects were observed of
      treatment on hematological parameters and concentrations of cortisol,
      haptoglobin, and P4. These observations suggest that intrauterine infusion of E.
      coli LPS moderately stimulates peripheral PMN function, but further research is
      needed to better understand the immunomodulatory effects of LPS in the uterus of
      cows with PVD.

PMID- 28434730
TI  - The effect of vitamin concentrates on the flavor of pasteurized fluid milk.
AB  - Fluid milk consumption in the United States continues to decline. As a result,
      the level of dietary vitamin D provided by fluid milk in the United States diet
      has also declined. Undesirable flavor(s)/off flavor(s) in fluid milk can
      negatively affect milk consumption and consumer product acceptability. The
      objectives of this study were to identify aroma-active compounds in vitamin
      concentrates used to fortify fluid milk, and to determine the influence of
      vitamin A and D fortification on the flavor of milk. The aroma profiles of 14
      commercial vitamin concentrates (vitamins A and D), in both oil-soluble and water
      dispersible forms, were evaluated by sensory and instrumental volatile compound
      analyses. Orthonasal thresholds were determined for 8 key aroma-active compounds
      in skim and whole milk. Six representative vitamin concentrates were selected to
      fortify skim and 2% fat pasteurized milks (vitamin A at 1,500-3,000 IU/qt,
      vitamin D at 200-1,200 IU/qt, vitamin A and D at 1,000/200-6,000/1,200 IU/qt).
      Pasteurized milks were evaluated by sensory and instrumental volatile compound
      analyses and by consumers. Fat content, vitamin content, and fat globule particle
      size were also determined. The entire experiment was done in duplicate. Water
      dispersible vitamin concentrates had overall higher aroma intensities and more
      detected aroma-active compounds than oil-soluble vitamin concentrates. Trained
      panelists and consumers were able to detect flavor differences between skim milks
      fortified with water-dispersible vitamin A or vitamin A and D, and unfortified
      skim milks. Consumers were unable to detect flavor differences in oil-soluble
      fortified milks, but trained panelists documented a faint carrot flavor in oil
      soluble fortified skim milks at higher vitamin A concentrations (3,000-6,000 IU).
      No differences were detected in skim milks fortified with vitamin D, and no
      differences were detected in any 2% milk. These results demonstrate that vitamin
      concentrates may contribute to off flavor(s) in fluid milk, especially in skim
      milk fortified with water-dispersible vitamin concentrates.

PMID- 28434731
TI  - A prospective cohort study of digital cushion and corium thickness. Part 2: Does
      thinning of the digital cushion and corium lead to lameness and claw horn
      disruption lesions?
AB  - The aim of this study was to determine whether a decrease in thickness of the
      sole soft tissues (SST) beneath the flexor tuberosity of the distal phalanx
      (i.e., the digital cushion and corium) predisposed a claw to develop claw horn
      disruption lesions (CHDL) or a leg to lameness. Data were analyzed from a
      longitudinal study of 179 cows, which had been examined at 5 assessment points 
      8, +1, +9, +17, and +29 wk relative to their first, second, third, or fourth
      calving. At each assessment point, SST were measured using ultrasonography.
      Additional assessment point data included sole lesions and back fat thickness
      (BFT), and cows had been locomotion scored every 2 wk from calving. One hundred
      fifty-eight cows completed the study. Separate logistic regression survival
      analyses were constructed to assess the outcomes, either lameness on a leg or
      CHDL on a claw; combinations of lameness and lesions were tested as outcomes. Cow
      level variables tested included farm and lactation number. Variables were tested
      describing previous SST thickness, minimum previous SST thickness, BFT, and
      change in either variable between prior assessment points. Prior lesions/lameness
      strongly predicted repeat cases and the final models had the outcome first lesion
      or lameness on a claw or leg. In the reported lameness models, lameness was
      defined as a leg being recorded as lame twice within 3 consecutive scores, and in
      the reported lesion models, lesion was defined as the first presence of either a
      sole ulcer or a severe sole hemorrhage on a claw. Thin SST increased the
      likelihood of lesion occurrence; thin SST on the lateral claw predicted
      subsequent lameness on a leg. Thin BFT and thinning of BFT between previous
      assessment points increased the likelihood of future lesion occurrence. Thin SST
      and thinning of BFT had additional effects on the likelihood of lesion
      occurrence, suggesting that BFT and sole SST had independent effects on lesion
      occurrence. However, change in SST thickness between assessment points did not
      influence the likelihood of future lesions or lameness. This suggests that thin
      SST were not simply a result of depletion of body fat and challenges the theory
      that thinning of the digital cushion with body fat mobilization leads to CHDL.
      Other possible mechanisms by which SST become thin are discussed and could
      include changes in integrity of the suspensory apparatus with physiological
      events.

PMID- 28434732
TI  - The effect of a furnished individual hutch pre-weaning on calf behavior, response
      to novelty, and growth.
AB  - Housing preweaned dairy calves in individual outdoor hutches is common in North
      America. However, this type of housing lacks stimulation and minimizes calves'
      ability to express natural behavior. Providing a social companion has been shown
      to stimulate natural behavior and promote growth, but no research has assessed
      the effect of providing physical enrichment items to calves pre-weaning. The
      objective of this study was to determine calf use of physical items added to an
      individual hutch, and if providing these items affected growth, behavior (e.g.,
      locomotor play and sucking on pen fixtures), and response to novelty after
      weaning. At birth, Jersey heifer calves were allocated to 1 of 2 types of
      hutches: furnished (n = 9 calves) or standard (n = 10 calves). Calves were housed
      in individual hutches on loose gravel and bedded with straw. The outdoor
      enclosure of furnished hutches contained 2 artificial teats, a stationary brush,
      a calf "lollie," and a rubber chain link for calves to manipulate. Calves were
      video-recorded continuously between 0800 and 2000 h twice weekly at 1, 3, 5, and
      7 wk of age; behavioral data were collected using the Noldus Observer software
      program (Noldus Inc., Wageningen, the Netherlands). At 63 d of age (after
      weaning), calf response to social and environmental novelty was tested. Starter
      consumption was measured daily, and calves were weighed at birth and weekly
      thereafter. Pre-weaning behavioral data were not normally distributed, so raw
      data were square-root-transformed before analysis. Calves used all of the items
      depending on the time of day, but they spent the most time using the brush.
      Calves housed in furnished hutches spent almost 50% more time engaged in
      locomotor play, but they spent the same amount of time sucking pen fixtures as
      calves housed in standard hutches. We observed no effect of treatment on growth,
      starter intake, or behavioral response to social and environmental novelty after
      weaning. Results suggest that providing some physical complexity to a standard
      hutch has some benefits for young calves, but further research is encouraged to
      determine the long-term effects of physical and social complexity for young dairy
      heifer calves.

PMID- 28434733
TI  - Short communication: Discrimination between retail bovine milks with different
      fat contents using chemometrics and fatty acid profiling.
AB  - We used a multivariate chemometric approach to differentiate or associate retail
      bovine milks with different fat contents and non-dairy beverages, using fatty
      acid profiles and statistical analysis. We collected samples of bovine milk
      (whole, semi-skim, and skim; n = 62) and non-dairy beverages (n = 27), and we
      analyzed them using gas-liquid chromatography. Principal component analysis of
      the fatty acid data yielded 3 significant principal components, which accounted
      for 72% of the total variance in the data set. Principal component 1 was related
      to saturated fatty acids (C4:0, C6:0, C8:0, C12:0, C14:0, C17:0, and C18:0) and
      monounsaturated fatty acids (C14:1 cis-9, C16:1 cis-9, C17:1 cis-9, and C18:1
      trans-11); whole milk samples were clearly differentiated from the rest using
      this principal component. Principal component 2 differentiated semi-skim milk
      samples by n-3 fatty acid content (C20:3n-3, C20:5n-3, and C22:6n-3). Principal
      component 3 was related to C18:2 trans-9,trans-12 and C20:4n-6, and its lower
      scores were observed in skim milk and non-dairy beverages. A cluster analysis
      yielded 3 groups: group 1 consisted of only whole milk samples, group 2 was
      represented mainly by semi-skim milks, and group 3 included skim milk and non
      dairy beverages. Overall, the present study showed that a multivariate
      chemometric approach is a useful tool for differentiating or associating retail
      bovine milks and non-dairy beverages using their fatty acid profile.

PMID- 28434734
TI  - Cow-level associations of lameness, behavior, and milk yield of cows milked in
      automated systems.
AB  - This study evaluated differences in behavior and productivity between lame and
      nonlame cows in herds with automated milking systems (AMS). We monitored 30 cows
      per herd on 41 farms with AMS in Canada (26 herds in Ontario and 15 herds in
      Alberta). During a 6-d period, milking data (n = 1,184) and lying behavior data
      (n = 1,209) were collected from cows on 41 farms. Rumination behavior (n = 569)
      and activity (n = 615) data were available for cows at 22 farms. Locomotion was
      scored using a numerical rating system (NRS; 1 = sound; 5 = extremely lame). Cows
      were defined as clinically lame with NRS >= 3 (n = 353, 29%) and nonlame with NRS
      < 3 (n = 865, 71%). Greater parity, lower body condition, and lower environmental
      temperature were factors associated with lameness. When accounting for other
      factors, lame cows produced 1.6 kg/d less milk in 0.3 fewer milkings/d. Lame cows
      were 2.2 times more likely to be fetched more than 1 time during the 6-d period
      and spent 38 min/d more time lying down in bouts that were 3.5 min longer in
      comparison with nonlame cows. As the number of cows per AMS unit increased, the
      frequency of milkings and refusals per cow per day decreased and cow activity
      increased. For each 13.3-percentage-point increase in freestall stocking density
      (cows per stall), daily lying time decreased by 13 min/d and cows were 1.6 times
      more likely to be fetched more than 1 time during the 6-d period. There was no
      difference in daily rumination or activity between lame and nonlame cows or in
      night:day rumination time, but lame cows had greater night:day activity ratios.
      This study supports the growing knowledge that lameness has negative effects on
      milk production, voluntary milking behavior, and lying behavior of cows in herds
      with AMS. These results may help dairy producers gain a better appreciation of
      the negative effects of even moderate cases of lameness and may help motivate
      them to improve their lameness monitoring and treatment protocols.

PMID- 28434736
TI  - Incidence of clinical mastitis and distribution of pathogens on large Chinese
      dairy farms.
AB  - Knowledge of the incidence of clinical mastitis (CM) and the distribution of
      pathogens involved is essential for development of prevention and control
      programs as well as treatment protocols. No country-wide study on the incidence
      of CM and the distribution of pathogens involved has been conducted in China.
      Core objectives of this study were, therefore, to determine the cumulative
      incidence of CM and the distribution of pathogens causing CM on large Chinese
      (>500 cows) dairy farms. In addition, associations between the distribution of CM
      pathogens and bedding materials and seasonal factors were also investigated.
      Bacterial culture was done on a total of 3,288 CM quarter milk samples from 161
      dairy herds (located in 21 provinces) between March 2014 and September 2016.
      Additional data, including geographical region of herds, herd size, bedding
      types, and number of CM cases during the last month, were also recorded. Mean
      cumulative incidence of CM was 3.3 cases per 100 cows per month (range = 1.7 to
      8.1). The most frequently isolated pathogens were Escherichia coli (14.4%),
      Klebsiella spp. (13.0%), coagulase-negative staphylococci (11.3%), Streptococcus
      dysgalactiae (10.5%), and Staphylococcus aureus (10.2%). Streptococcus agalactiae
      was isolated from 2.8% of CM samples, whereas Streptococcus uberis were isolated
      from 2.1% of samples, and 15.8% of 3,288 samples were culture-negative. Coagulase
      negative staphylococci, E. coli, and other Enterobacter spp. were more frequently
      isolated in the northwest than the northeast or south of China. Streptococcus
      dysgalactiae, other streptococci, and Strep. agalactiae were more frequently
      isolated in winter (October-March), whereas E. coli and Klebsiella spp. were
      mostly isolated in summer (April-September). Streptococcus dysgalactiae was more
      often isolated from CM cases of herds using sand bedding, whereas Klebsiella spp.
      and other streptococci were more common in herds using organic bedding. The
      incidence of CM and distribution of pathogens differed among herds and better
      mastitis management is needed. Furthermore, geography, bedding materials, and
      season should be included when designing mastitis control and prevention schemes
      for Chinese dairies.

PMID- 28434735
TI  - Effects of graded removal of lysine from an intravenously infused amino acid
      mixture on lactation performance and mammary amino acid metabolism in lactating
      goats.
AB  - To investigate responses of milk protein synthesis and mammary AA metabolism to a
      graded decrease of postruminal Lys supply, 4 lactating goats fitted with jugular
      vein, mammary vein, and carotid artery catheters and transonic blood flow
      detectors on the external pudic artery were used in a 4 * 4 Latin square
      experiment. Goats were fasted for 24 h and then received a 9-h intravenous
      infusion of an AA mixture plus glucose. Milk yield was recorded and samples were
      taken in h 2 to 8 of the infusion period; a mammary biopsy was performed in the
      last hour. Treatments were graded decrease of lysine content in the infusate to
      100 (complete), 60, 30, or 0% as in casein. Lysine-removed infusions linearly
      decreased milk yield, tended to decrease lactose yield, and tended to increase
      milk fat to protein ratio. Milk protein content and yield were linearly decreased
      by graded Lys deficiency. Mammary Lys uptake was concomitantly decreased, but
      linear regression analysis found no significant relationship between mammary Lys
      uptake and milk protein yield. Treatments had no effects on phosphorylation
      levels of the downstream proteins measured in the mammalian target or rapamycin
      pathway except for a tended quadratic effect on that of eukaryotic initiation
      factor 2, which was increased and then decreased by graded Lys deficiency.
      Removal of Lys from the infusate linearly increased circulating glucagon and
      glucose. Removal of Lys from the infusate linearly decreased arterial and venous
      concentrations of Lys. Treatments also had a significant quadratic effect on
      venous Lys, suggesting mechanisms to stabilize circulating Lys at a certain
      range. The 2 infusions partially removing Lys resulted in a similar 20% decrease,
      whereas the 0% Lys infusion resulted in an abrupt 70% decrease in mammary Lys
      uptake compared with that of the full-AA mixture infusion. Consistent with the
      abrupt decrease, mammary Lys uptake-to-output ratio decreased from 2.2 to 0.92,
      suggesting catabolism of Lys in the mammary gland could be completely prevented
      when the animal faced severe Lys deficiency. Mammary blood flow was linearly
      increased, consistent with the linearly increased circulating nitric oxide by
      graded Lys deficiency, indicating mechanisms to ensure the priority of the
      mammary gland in acquiring AA for milk protein synthesis. Infusions with Lys
      removed increased mammary clearance rate of Lys numerically by 2 to 3 fold. In
      conclusion, the decreased milk protein yield by graded Lys deficiency was mainly
      a result of the varied physiological status, as indicated by the elevated
      circulating glucagon and glucose, rather than a result of the decreased mammary
      Lys uptake or depressed signals in the mTOR pathway. Mechanisms of Lys deficiency
      to promote glucagon secretion and mammary blood flow and glucagon to depress milk
      protein synthesis need to be clarified by future studies.

PMID- 28434737
TI  - Short communication: Microbiological quality of raw cow milk and its association
      with herd management practices in Northern China.
AB  - Contamination of raw milk with bacterial pathogens is potentially hazardous to
      human health. The aim of this study was to evaluate the total bacteria count
      (TBC) and presence of pathogens in raw milk in Northern China along with the
      associated herd management practices. A total of 160 raw milk samples were
      collected from 80 dairy herds in Northern China. All raw milk samples were
      analyzed for TBC and pathogens by culturing. The results showed that the number
      of raw milk samples with TBC <2 * 106 cfu/mL and <1 * 105 cfu/mL was 146 (91.25%)
      and 70 (43.75%), respectively. A total of 84 (52.50%) raw milk samples were
      Staphylococcus aureus positive, 72 (45.00%) were Escherichia coli positive, 2
      (1.25%) were Salmonella positive, 2 (1.25%) were Listeria monocytogenes positive,
      and 3 (1.88%) were Campylobacter positive. The prevalence of S. aureus was
      influenced by season, herd size, milking frequency, disinfection frequency, and
      use of a Dairy Herd Improvement program. The TBC was influenced by season and
      milk frequency. The correlation between TBC and prevalence of S. aureus or E.
      coli is significant. The effect size statistical analysis showed that season and
      herd (but not Dairy Herd Improvement, herd size, milking frequency, disinfection
      frequency, and area) were the most important factors affecting TBC in raw milk.
      In conclusion, the presence of bacteria in raw milk was associated with season
      and herd management practices, and further comprehensive study will be powerful
      for effectively characterizing various factors affecting milk microbial quality
      in bulk tanks in China.

PMID- 28434738
TI  - Relationships among superantigen toxin gene profiles, genotypes, and pathogenic
      characteristics of Staphylococcus aureus isolates from bovine mastitis.
AB  - Staphylococcus aureus is one of the major etiological agents of bovine mastitis,
      harboring a wide variety of staphylococcal superantigen (SAg) toxin genes. The
      SAg toxin genes are reported to be closely associated with the pathogenicity of
      the Staph. aureus causing the bovine mastitis. This study was conducted to
      investigate SAg toxin gene profiles and to assess the relationships among SAg
      toxin genes, genotypes of Staph. aureus, and their pathogenic properties. A total
      of 327 quarter milk samples were collected from bovine mastitis cases for
      isolation and identification of pathogens. In total, 35 isolates were identified
      as Staph. aureus, and the prevalence of Staph. aureus in milk samples was 13.6%
      (35/256). Polymerase chain reaction (PCR) and randomly amplified polymorphic DNA
      (RAPD) assays were used to detect the SAg toxin genes and to genotype Staph.
      aureus strains isolated from milk samples of bovine mastitis in 10 dairy herds
      located in Ningxia, China, respectively. The results showed that among the Staph.
      aureus isolates (n = 35), 71.4% (n = 25) of isolates carried at least one SAg
      toxin gene. In total, 18 SAg genes and 21 different gene combination patterns
      were detected among these isolates. The most common SAg genes in Staph. aureus
      isolates were sei, sen, and seu (44.0% each), followed by seo, tst, and etB
      (28.0% each), etA (24.0%), sem and sep (16.0% each), seb, sec, sed, and sek
      (12.0% each), and sea and seh genes (8.0% each); the seg, sej, and ser genes were
      present in 4.0% of the isolates. Three gene combinations were found to be related
      to mobile genetic elements that carried 2 or more genes. The egc-cluster of the
      seg-sei-sem-sen-seo genes, located on the pathogenicity island Type I
      upsilonSabeta, was detected in 16% of isolates. Interestingly, we observed 6 RAPD
      genotypes (I to VI) in Staph. aureus isolates, and 2 of these genotypes were
      strongly associated with the severity of bovine mastitis; there was a close
      relationship between the RAPD genotypes and SAg genes. Isolates of RAPD type III
      were more frequently associated with clinical and subclinical mastitis, whereas
      strains of type VI were mostly related to subclinical mastitis. In addition, SAg
      genes were related to severity of bovine mastitis. We conclude that an obvious
      relationship exists among RAPD genotypes, SAg toxin genes, and severity of bovine
      mastitis.

PMID- 28434739
TI  - The effect of conjugated linoleic acid, acetate, and their interaction on adipose
      tissue lipid metabolism in nonlactating cows.
AB  - During biohydrogenation-induced milk fat depression, adipose tissue lipogenesis
      may be increased through nutrients spared from milk fat synthesis. However, the
      direct effect of trans-10,cis-12 conjugated linoleic acid (CLA) and the indirect
      effect of spared nutrients on adipose tissue lipogenesis during milk fat
      depression is not clear. The objective of this study was to determine the direct
      effect of CLA, spared acetate, and their interaction on adipose tissue
      lipogenesis using nonlactating dairy cows as an experimental model, which allows
      separation of the effect of CLA and nutrient sparing. Eight ruminally cannulated,
      multiparous nonlactating and pregnant Holstein cows were randomly assigned to
      treatments in a 4 * 4 Latin square design with a 2 * 2 factorial arrangement of
      treatments. Factors were CLA and acetate, and treatments were control (CON),
      rumen acetate infusions (Ac; continuous infusion of 7 mol/d adjusted to pH 6.1
      with sodium hydroxide), abomasal infusion of trans-10,cis-12 CLA (CLA; 10 g/d of
      both trans-10,cis-12 CLA and cis-9,trans-11 CLA), and Ac + CLA (Ac + CLA). Dry
      matter intake was not affected by Ac, but tended to decrease by CLA. Plasma trans
      10,cis-12 CLA concentration as a percentage of fatty acids was increased by 0.3
      percentage points by CLA. No treatment effect was observed on plasma glucose and
      beta-hydroxybutyrate, but an interaction was observed of CLA and Ac on plasma
      insulin and nonesterified fatty acids. Insulin was increased 24% by CLA, but not
      by Ac + CLA, and nonesterified fatty acids were increased 55% by Ac + CLA, but
      not by CLA alone. Lipogenesis and oxidation capacity of adipose tissue explants
      were not affected by treatments. Adipose expression of key lipogenic factors
      (peroxisome proliferator-activated receptor gamma2 and sterol response element
      binding protein 1c) were reduced by CLA, by the interaction of Ac and CLA (sterol
      response element binding protein 1c), and tended to be reduced with Ac (S14 and
      peroxisome proliferator-activated receptor gamma1). Expression of several adipose
      lipogenic enzymes (fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA
      desaturase 1) was reduced by CLA and Ac. An interaction was observed of Ac and
      CLA for fatty acid binding protein 4, which was decreased by Ac, but not Ac +
      CLA. In conclusion, in the nonlactating cow, adipose tissue is sensitive to the
      anti-lipogenic effects of trans-10,cis-12 CLA at the transcription level and
      acetate does not stimulate lipogenesis.

PMID- 28434740
TI  - Effects of prepartum dietary cation-anion difference on aspects of peripartum
      mineral and energy metabolism and performance of multiparous Holstein cows.
AB  - The objectives of this study were to determine the effect of decreasing dietary
      cation-anion difference [DCAD; (Na+ + K+) - (Cl- + S2-)] of the prepartum diet on
      aspects of mineral metabolism, energy metabolism, and performance of peripartum
      dairy cows. Multiparous Holstein cows (n = 89) were enrolled between 38 and 31 d
      before expected parturition and randomized to treatments in a completely
      randomized design (restricted to balance for previous 305-d mature equivalent
      milk production, parity, and body condition score) at 24 d before expected
      parturition. Treatments consisted of a low-K ration without anion supplementation
      [CON; n = 30, DCAD = +18.3 mEq/100 g of dry matter (DM)]; partial anion
      supplementation to a low-K ration (MED; n = 30, DCAD = +5.9 mEq/100 g of DM); and
      anion supplementation to a low-K ration to reach a targeted average urine pH
      between 5.5 and 6.0 (LOW; n = 29, DCAD = -7.4 mEq/100 g of DM). Cows were fed a
      common postpartum diet and data collected through 63 d in milk. Urine pH (CON =
      8.22, MED = 7.89, and LOW = 5.96) was affected quadratically by decreasing
      prepartum DCAD. A linear relationship between urine pH and urine Ca:creatinine
      ratio was observed (r = -0.81). Plasma Ca concentrations in the postpartum period
      (d 0 to 14; CON = 2.16, MED = 2.19, and LOW = 2.27 mmol/L) were increased
      linearly with decreasing prepartum DCAD. A treatment by parity (second vs. third
      and greater) interaction for postpartum plasma Ca concentration suggested that
      older cows had the greatest response to the low DCAD diet and older cows fed LOW
      had decreased prevalence of hypocalcemia after calving. A quadratic effect of
      decreasing DCAD on prepartum DMI was observed (CON = 13.6, MED = 14.0, and LOW =
      13.2 kg/d). Milk production in the first 3 wk postpartum was increased linearly
      with decreasing DCAD (CON = 40.8, MED = 42.4, and LOW = 43.9 kg/d) and DMI in
      this period also tended to linearly increase (CON = 20.2, MED = 20.9, and LOW =
      21.3 kg/d). Overall, effects on intake and milk yield analyzed over wk 1 to 9
      postpartum were not significant. This study demonstrates that feeding lower DCAD
      diets prepartum improves plasma Ca status in the immediate postpartum period and
      results in increased DMI and milk production in the 3 wk after parturition.
      Compared with no anion supplementation or lower levels of anion supplementation,
      greater improvements were observed with the lower DCAD feeding strategy, in which
      an average urine pH of 5.5 to 6.0 was targeted.

PMID- 28434741
TI  - Dietary linseed oil increases trans-10,cis-15 18:2 in caprine milk fat.
AB  - Trans-10,cis-15 18:2 has been recently detected and characterized in digestive
      contents and meat and adipose tissue of ruminants, but its presence in milk and
      dairy products is hardly known. The aim of this study was to quantify trans
      10,cis-15 18:2 in milk fat, better understand its metabolic origin, and help to
      elucidate the mechanisms of rumen biohydrogenation when the diet composition
      might affect ruminal environment. To address these objectives, 16 dairy goats
      were allocated to 2 simultaneous experiments (2 groups of goats and 2 treatments
      in each experiment). Experimental treatments consisted of basal diets with the
      same forage-to-concentrate ratio (33/67) and 2 starch-to-nonforage neutral
      detergent fiber (NDF) ratios (0.8 and 3.1), which were supplemented or not with
      30 g/d of linseed oil for 25 d in a crossover design. Trans-10,cis-15 18:2
      contents in milk fat were determined by gas chromatography fitted with an
      extremely polar capillary column (SLB-IL111). Levels of trans-10,cis-15 18:2 in
      individual milk fat samples ranged from 0 to 0.2% of total fatty acids, and its
      content in milk fat increased 8 fold due to linseed oil supplementation,
      substantiating the predominant role of alpha-linolenic acid in its formation. The
      trans-10,cis-15 18:2 levels in milk fat were similar in both experiments, despite
      the fact starch-to-nonforage NDF ratio of their respective basal diets greatly
      differed. In conclusion, trans-10,cis-15 18:2 was clearly related to linseed oil
      supplementation, and its increase in milk fat was comparable when the basal diets
      were rich in either nonforage NDF or starch.

PMID- 28434742
TI  - Endocrine and metabolic changes in transition dairy cows are affected by
      prepartum infusions of a serotonin precursor.
AB  - Serotonin (5-HT) has been shown to be involved in calcium homeostasis, modulating
      calcium concentration in blood. In addition, 5-HT participates in a variety of
      metabolic pathways, mainly through the modulation of glucose and lipid
      metabolism. The hypothesis of the present study was that the prepartum
      administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, would affect
      endocrine systems related to calcium homeostasis, and interact with other
      endocrine and metabolic pathways during the transition period. In this study, 20
      Holstein dairy cows were randomly assigned to 2 experimental groups. Both groups
      received a daily i.v. infusion of 1 L of either 0.9% NaCl (control group; n = 10)
      or 0.9% NaCl containing 1 mg of 5-HTP/kg of BW (5-HTP group, n = 10). Infusions
      started d 10 before estimated parturition date and ended the day of parturition,
      resulting in a minimum of 4 d of infusion (8.4 +/- 0.7 d of infusion). Until
      parturition, blood samples were collected before the daily infusions, and
      postpartum daily until d 7, and on d 30. Plasma concentrations of parathyroid
      hormone (PTH) were transiently increased at parturition and on d 1 in control
      cows. In the 5-HTP group PTH remained unchanged. The concentration of
      pyridinoline (PYD), an established marker for calcium release from the bone to
      the bloodstream, increased on d 1 postpartum only in the 5-HTP group. In control
      cows, PYD concentrations did not change on d 1 postpartum. Melatonin
      concentrations were slightly but significantly increased in the 5-HTP group
      compared with the control group. Insulin concentrations decreased in both groups
      postpartum. Before parturition, leptin concentrations decreased in both groups
      and remained at this level until d 30 postpartum. Plasma IgG concentrations
      decreased in both groups on d -1 postpartum. Haptoglobin increased in both groups
      on d -1 and remained at this level until d 7 postpartum. No differences between
      groups were observed for insulin, glucagon, IgG, leptin, adiponectin, and
      haptoglobin concentrations. The results obtained in the present study evidenced
      that 5-HT is regulating calcium homeostasis independent of PTH. The lack of
      treatment effects on IgG and on other hormones and metabolites indicates that 5
      HTP did not affect these other metabolic pathways and the IgG concentration
      during the transition period.

PMID- 28434743
TI  - The effect of emulsifying salts on the turbidity of a diluted milk system with
      varying pH and protein concentration.
AB  - Solutions of 10 commonly used emulsifying salts (ES) listed in the Code of
      Federal Regulations (21CFR133.179) for pasteurized process cheese were tested for
      their effect on the turbidity of a diluted milk system at different pH and
      protein concentrations to characterize the conditions that affect micellar
      structure. Emulsifying salt solutions were made by mixing the ES in a 1-in-20
      dilution of water in skim milk ultrafiltrate (3 kDa molecular weight cut-off) to
      obtain ES concentrations from 0 to 248 mM. Skim milk was added to solutions
      containing nanopure water, skim milk ultrafiltrate, and a specific ES ranging in
      concentration from 0 to 248 mM and pH 5, 5.8, 6.8, 7.8, and 8.8. The turbidity of
      the samples was measured as the optical density at 400 nm immediately after
      mixing (time, t = 0), after 30 s (t = 30s), and after 30 min (t = 30min).
      Emulsifying salts were found to cause a decrease in the turbidity of the system,
      which was modeled using an exponential decay model, where C* represents a
      threshold salt concentration at which rapid dissociation occurs. At pH values 5.8
      and 6.8, the ES caused the greatest decrease in turbidity of the diluted milk
      system. At pH 5, the ES had the least effect on the turbidity of the system.
      Sodium hexametaphosphate was found to have the strongest dissociative effect,
      with a C* value of 0.33 mM for t = 0 at pH 6.8. In contrast, the largest C* value
      calculated at pH 6.8 was monosodium phosphate at 278.22 mM. Increased time
      resulted in lower C* values. The model established for this study can be used to
      predict the dissociation of casein micelles in the presence of various types of
      ES.

PMID- 28434744
TI  - A prospective cohort study of digital cushion and corium thickness. Part 1:
      Associations with body condition, lesion incidence, and proximity to calving.
AB  - Claw horn disruption lesions (CHDL) are a major cause of lameness in dairy cattle
      and are likely a result of excessive forces being applied to the germinal
      epithelium that produces the claw horn. The digital cushion is a connective
      tissue structure, containing depots of adipose tissue, that sits beneath the
      distal phalanx and has been shown to be thicker in fatter cows. Body condition
      score (BCS) loss is a risk factor for CHDL, and one possible explanation is that
      fat is mobilized from the digital cushion during negative energy balance, causing
      the digital cushion to thin and lose force-dissipating capacity, leading to
      disruption of claw horn growth. This prospective cohort study investigated the
      association between measures of body fat and sole soft tissue (SST) thickness (a
      combined measure of the corium and digital cushion beneath the distal phalanx) in
      a longitudinal manner. The SST of 179 cows in 2 high-yielding dairy herds were
      measured at 5 assessment points between 8 wk before and 35 wk postcalving. The
      BCS, back fat thickness (BFT), and lesion incidence were recorded. Data were
      analyzed in a 4-level mixed effects regression model, with the outcome being SST
      thickness beneath the flexor tuberosity of the distal phalanx. Data from 827
      assessment points were available for analysis. The overall mean of SST was 4.99
      mm (standard deviation: 0.95). The SST was thickest 8 wk before calving (5.22 mm,
      standard deviation: 0.91) and thinnest 1 wk postcalving (4.68 mm, standard
      deviation: 0.87), suggesting an effect of calving on SST. The BFT was positively
      correlated with SST in the model with a small effect size (a 10 mm decrease in
      BFT corresponded with a 0.13 mm decrease in SST), yet the nadir of BFT was 11.0
      mm at 9 to 17 wk postcalving (when SST was ~4.95 mm), rather than occurring with
      the nadir of SST immediately after calving. The SST also varied with other
      variables [e.g., cows that developed a sole ulcer or severe sole hemorrhage
      during the study had thinner SST (-0.24 mm)], except when a sole ulcer was
      present, when it was thicker (+0.53 mm). Cows that developed lesions had a
      thinner digital cushion before the lesion occurrence, which became thickened with
      sole ulcer presence, perhaps representing inflammation. Furthermore, although BFT
      was correlated with SST over time, SST may also have been influenced by other
      factors such as integrity of the suspensory apparatus, which could have a major
      effect on CHDL. Measures of body fat likely contributed to having thin SST, but
      other factors including calving, herd, and lesion presence also had an effect.

PMID- 28434745
TI  - Hot topic: 16S rRNA gene sequencing reveals the microbiome of the virgin and
      pregnant bovine uterus.
AB  - We tested the hypothesis that the uterus of virgin heifers and pregnant cows
      possessed a resident microbiome by 16S rRNA gene sequencing of the virgin and
      pregnant bovine uterus. The endometrium of 10 virgin heifers in estrus and the
      amniotic fluid, placentome, intercotyledonary placenta, cervical lumen, and
      external cervix surface (control) of 5 pregnant cows were sampled using aseptic
      techniques. The DNA was extracted, the V4 hypervariable region of the 16S rRNA
      gene was amplified, and amplicons were sequenced using Illumina MiSeq technology
      (Illumina Inc., San Diego, CA). Operational taxonomic units (OTU) were generated
      from the sequences using Qiime v1.8 software, and taxonomy was assigned using the
      Greengenes database. The effect of tissue on the microbial composition within the
      pregnant uterus was tested using univariate (mixed model) and multivariate
      (permutational multivariate ANOVA) procedures. Amplicons of 16S rRNA gene were
      generated in all samples, supporting the contention that the uterus of virgin
      heifers and pregnant cows contained a microbiome. On average, 53, 199, 380, 382,
      525, and 13,589 reads annotated as 16, 35, 43, 63, 48, and 176 OTU in the
      placentome, virgin endometrium, amniotic fluid, cervical lumen, intercotyledonary
      placenta, and external surface of the cervix, respectively, were generated. The 3
      most abundant phyla in the uterus of the virgin heifers and pregnant cows were
      Firmicutes, Bacteroidetes, and Proteobacteria, and they accounted for
      approximately 40, 35, and 10% of the sequences, respectively. Phyla abundance was
      similar between the tissues of the pregnant uterus. Principal component analysis,
      one-way PERMANOVA analysis of the Bray-Curtis similarity index, and mixed model
      analysis of the Shannon diversity index and Chao1 index demonstrated that the
      microbiome of the control tissue (external surface of the cervix) was
      significantly different from that of the amniotic fluid, intercotyledonary
      placenta, and placentome tissues. Interestingly, many bacterial species
      associated with postpartum uterine disease (i.e., Trueperella spp., Acinetobacter
      spp., Fusobacteria spp., Proteus spp., Prevotella spp., and Peptostreptococcus
      spp.) were also present in the uterus of virgin heifers and of pregnant cows. The
      presence of 16S rRNA gene sequence reads in the samples from the current study
      suggests that the uterine microbiome is established by the time a female reaches
      reproductive maturity, and that pregnancies are established and maintained in the
      presence of a uterine microbiome.

PMID- 28434746
TI  - Supplementing an immunomodulatory feed ingredient to modulate thermoregulation,
      physiologic, and production responses in lactating dairy cows under heat stress
      conditions.
AB  - This study compared vaginal temperature, physiologic, and productive parameters
      in lactating dairy cows supplemented or not with Omnigen-AF (Phibro Animal
      Health, Teaneck, NJ) during the summer months in a tropical environment. Thirty
      two lactating, primiparous (n = 16) and multiparous (n = 16) pregnant Holstein *
      Gir cows were ranked by parity, days in milk, body weight, and body condition
      score (BCS), and assigned to receive (SUPP; n = 16) or not (CON; n = 16) Omnigen
      AF (Phibro Animal Health, Teaneck, NJ) at 56 g/cow daily (as-fed basis). During
      the experimental period (d -6 to 56), cows were maintained in a single drylot pen
      with ad libitum access to water and a total mixed ration, and milked twice daily.
      Cows received Omnigen-AF mixed with 200 g of corn (as-fed basis) after the daily
      morning milking through self-locking head gates, whereas CON cows concurrently
      received 56 g of kaolin mixed with 200 g of corn. For feed intake evaluation,
      cows from both treatments were randomly divided in 4 groups of 8 cows each, and
      allocated to 8 individual feeding stations for 3 d. Intake was evaluated 4 times
      per group from d 1 to 56. From d -6 to 0, d 15 to 28, and d 43 to 56, cow vaginal
      temperature was recorded hourly. Environmental temperature-humidity index (THI)
      was also recorded hourly from d 15 to 28 and d 43 to 56. Cows were evaluated for
      body weight and BCS on d -6 and 56, individual milk production was recorded daily
      from d -6 to 56, and milk samples were collected on d -6, 0, 7, 14, 21, 28, 35,
      42, 49, and 56 for analyses of somatic cell count and milk components. Blood
      samples were collected on d -6, -3, 0, 9, 15, 18, 21, 24, 27, 36, 45, 48, 51, 54,
      and 56. Results from samples or observations collected from d -6 to 0 were
      included as an independent covariate in each respective analysis. Environmental
      THI was 74.2 +/- 0.5 and cows were exposed to THI >68 for 633 h within a total of
      672 h of evaluation. Cows assigned to CON had greater vaginal temperature on d
      28, 43, 45, and from d 48 to 55 (by 0.38 to 0.52%), as well as greater mean
      somatic cell count (by 97%) and serum haptoglobin concentrations (by 89%)
      compared with SUPP cows. Cows assigned to SUPP had greater mean dry matter intake
      (by 7%), BCS on d 56 (by 11%), and mean serum insulin concentrations (by 35%)
      compared with CON cows. Hence, SUPP ameliorated hyperthermia, improved
      nutritional status, and modulated systemic and mammary gland immune parameters in
      lactating dairy cows exposed to heat stress conditions.

PMID- 28434747
TI  - Bivariate threshold models for genetic evaluation of susceptibility to and
      ability to recover from mastitis in Danish Holstein cows.
AB  - Mastitis in dairy cows is an unavoidable problem and genetic variation in
      recovery from mastitis, in addition to susceptibility, is therefore of interest.
      Genetic parameters for susceptibility to and recovery from mastitis were
      estimated for Danish Holstein-Friesian cows using data from automatic milking
      systems equipped with online somatic cell count measuring units. The somatic cell
      count measurements were converted to elevated mastitis risk, a continuous
      variable [on a (0-1) scale] indicating the risk of mastitis. Risk values >0.6
      were assumed to indicate that a cow had mastitis. For each cow and lactation, the
      sequence of health states (mastitic or healthy) was converted to a weekly
      transition: 0 if the cow stayed within the same state and 1 if the cow changed
      state. The result was 2 series of transitions: one for healthy to diseased (HD,
      to model mastitis susceptibility) and the other for diseased to healthy (DH, to
      model recovery ability). The 2 series of transitions were analyzed with bivariate
      threshold models, including several systematic effects and a function of time.
      The model included effects of herd, parity, herd-test-week, permanent environment
      (to account for the repetitive nature of transition records from a cow) plus two
      time-varying effects (lactation stage and time within episode). In early
      lactation, there was an increased risk of getting mastitis but the risk remained
      stable afterwards. Mean recovery rate was 45% per lactation. Heritabilities were
      0.07 [posterior mean of standard deviations (PSD) = 0.03] for HD and 0.08 (PSD =
      0.03) for DH. The genetic correlation between HD and DH has a posterior mean of 
      0.83 (PSD = 0.13). Although susceptibility and recovery from mastitis are
      strongly negatively correlated, recovery can be considered as a new trait for
      selection.

PMID- 28434748
TI  - Predicting stage 2 of calving in Holstein-Friesian heifers.
AB  - The objective of this study was to predict stage 2 of calving in Holstein
      Friesian heifers. Interobserver reliability and predictive values of relevant
      signs of imminent parturition (i.e., tail raising, stepping, clear and bloody
      vaginal discharge, turning the head toward the abdomen, and lying lateral with
      abdominal contractions) were determined. In the first experiment 32 heifers were
      included. Three investigators participated as observers in the study. They walked
      through the precalving pen in pairs and observed pregnant heifers (>=267 d
      pregnant). Cohen's kappa results for the interobserver reliability were between
      0.51 and 0.91. Thirty-seven Holstein-Friesian heifers were enrolled in the second
      experiment. Heifers were observed hourly for 24 h/d. Signs of imminent
      parturition that occurred were noted on a checklist. Compared with a precalving
      control period (4 d before calving), tail raising, clear vaginal discharge, and
      bloody vaginal discharge were more likely to occur during the last 24 h before
      calving. Two equations were built using the GENLINMIXED procedure to predict the
      hours until parturition. In version 1, the absence or presence of each sign of
      imminent parturition except turning the head toward the abdomen was included. In
      version 2, hours until parturition were estimated with the factors days of
      gestation, tail raising, and clear vaginal discharge. Relaxation of the broad
      pelvic ligaments and teat filling were evaluated twice per day. Prediction of
      calving with these parameters was not satisfying (positive predictive values were
      between 35.1 and 72.7% depending on the day of gestation). The possibility of
      excluding calving for the next 12 h was considerably higher, ranging from 88.5 to
      97.1%. These results indicate that predicting stage 2 of calving via direct
      observation of plausible signs is imprecise and therefore not recommendable.

PMID- 28434749
TI  - Short communication: Muscle protein synthetic response to microparticulated whey
      protein in middle-aged men.
AB  - Whey protein concentrate (WPC) is a high-quality dairy ingredient that is often
      included in formulated food products designed to stimulate muscle anabolism. Whey
      protein concentrate can be affected by UHT processing, and its sensory properties
      are not compatible with some formulated food products. Microparticulated WPC
      (mWPC) is a novel ingredient that is resistant to heat treatment and has enhanced
      sensory properties. When 16 healthy middle-aged men consumed 20 g of either WPC
      or mWPC, both proteins increased plasma essential AA and leucine concentrations
      with no detectable difference in curve kinetics. Myofibrillar protein synthesis
      was increased in both groups for 90 min after ingestion with no difference
      between groups. Ingestion of mWPC resulted in a muscle anabolic response that was
      equivalent to that of WPC over the full 210-min measurement period. Formulated
      products incorporating mWPC or standard WPC would provoke equivalent anabolic
      responses.

PMID- 28434750
TI  - Integrating an automated activity monitor into an artificial insemination program
      and the associated risk factors affecting reproductive performance of dairy cows.
AB  - The aim of this study was to compare 2 reproductive programs for the management
      of first postpartum artificial insemination (AI) based on activity monitors and
      timed AI, as well as to determine the effect of health-related factors on
      detection and expression of estrus. Lactating Holstein cows (n = 918) from 2
      commercial farms were enrolled. Estrous cycles of all cows were presynchronized
      with 2 injections of PGF2alpha administered 2 wk apart. Treatments were (1) first
      insemination performed by timed AI (TAI) and (2) first insemination based upon
      the detection of estrus by activity monitors (ACT; Heatime, SCR Engineering,
      Netanya, Israel) after the presynchronization, whereas cows not inseminated by
      the detection of estrus were enrolled in the Ovsynch protocol. Body condition
      score (BCS; scale 1 to 5), hock score (scale: 1 to 4), gait score (scale: 1 to
      4), and corpus luteum presence detected by ovarian ultrasonography were recorded
      twice during the presynchronization. On the ACT treatment, 50.5% of cows were
      inseminated based on detected estrus, whereas 83.2% of the cows on the TAI
      treatment were inseminated appropriately after the timed AI protocol. Pregnancy
      per AI did not differ by treatment (30.8 vs. 33.5% for ACT and TAI,
      respectively). Success of pregnancy was affected by parity, cyclicity, BCS, milk
      production, and a tendency for leg health. In addition, treatment * cyclicity and
      treatment * parity interactions were found to affect pregnancy success, where
      anovulatory cows and older cows had compromised pregnancy outcomes on the ACT
      treatment but not on the TAI treatment. Factors affecting pregnancy outcomes
      varied among farms. Hazard of pregnancy by 300 DIM was affected by farm, parity,
      BCS, a treatment * cyclicity interaction, and a tendency for an interaction
      between leg health and farm. Detection of estrus was affected by farm, parity,
      cyclicity, and leg health, but not BCS or milk production. Expression of estrus
      was compromised in anovular and older cows, and by the timing of the estrus
      event, but not by gait score, BCS, or milk production. Increased duration of
      estrus, but not intensity of estrus, improved pregnancy per AI. In conclusion,
      using an automated activity monitor for the detection of estrus within a Presynch
      Ovsynch program resulted in similar pregnancy per AI and days open compared with
      a reproduction program that was strictly based on timed AI for first postpartum
      AI. In contrast, notable variations in reproductive outcomes were detected
      between farms, suggesting that the use of automated activity monitors is prone to
      individual farm management.

PMID- 28434751
TI  - Genome-wide mapping and estimation of inbreeding depression of semen quality
      traits in a cattle population.
AB  - Inbreeding depression is known to affect quantitative traits such as male
      fertility and sperm quality, but the genetic basis for these associations is
      poorly understood. Most studies have been limited to examining how pedigree- or
      marker-derived genome-wide autozygosity is associated with quantitative
      phenotypes. In this study, we analyzed possible associations of genetic features
      of inbreeding depression with percentage of live spermatozoa and total number of
      spermatozoa in 19,720 ejaculates obtained from 554 Austrian Fleckvieh bulls
      during routine artificial insemination programs. Genome-wide inbreeding
      depression was estimated and genomic regions contributing to inbreeding
      depression were mapped. Inbreeding depression did affect total number of
      spermatozoa, and such depression was predicted by pedigree-based inbreeding
      levels and genome-wide inbreeding levels based on runs of homozygosity (ROH).
      Genome-wide inbreeding depression did not seem to affect percentage of live
      spermatozoa. A model incorporating genetic effects of the bull, environmental
      factors, and additive genetic and ROH status effects of individual single
      nucleotide polymorphisms revealed genomic regions significantly associated with
      ROH status for total number of spermatozoa (4 regions) or percentage of live
      spermatozoa (5 regions). All but one region contains genes related to
      spermatogenesis and sperm morphology. These genomic regions contain genes
      affecting sperm morphogenesis and efficacy. The results highlight that next
      generation sequencing may help explain some of the genetic factors contributing
      to inbreeding depression of sperm quality traits in Fleckvieh bulls.

PMID- 28434752
TI  - Effects of intrauterine infusion of Escherichia coli lipopolysaccharide on
      uterine health, resolution of purulent vaginal discharge, and reproductive
      performance of lactating dairy cows.
AB  - The objectives of the current experiment were to evaluate the effects of
      intrauterine infusion of Escherichia coli lipopolysaccharide (LPS) in cows
      diagnosed with purulent vaginal discharge (PVD) on intrauterine cell population,
      resolution of PVD, uterine health, and reproductive performance. Jersey cows (n =
      3,084) were examined using the Metricheck device to diagnose PVD at 35 +/- 6 d
      postpartum. Purulent vaginal discharge was defined as the presence of purulent
      (>=50% pus) discharge detectable in the vagina. Of the 310 cows positive for PVD,
      267 cows were enrolled in the current experiment. To ensure proper timing of
      treatment and collection of samples, only 9 PVD-positive cows were treated per
      day. Selected cows were balanced at 35 +/- 6 d postpartum for lactation number,
      body condition score, and milk yield and were randomly assigned to receive an
      intrauterine infusion of 20 mL of phosphate-buffered saline (PBS; control, n =
      87), 20 mL of PBS with 150 ug LPS (LPS150, n = 91), or 20 mL of PBS with 300 ug
      of LPS (LPS300, n = 89). Uterine cytology was performed immediately before
      treatment and 1, 2, and 7 d after treatment to evaluate the effect of LPS
      treatment on intrauterine cell population. Cows were examined with the Metricheck
      device at 7 and 28 d after treatment to evaluate the effects of treatment on
      resolution of PVD. Reproductive status was recorded up to 200 d postpartum. Cows
      diagnosed with PVD had greater incidence of twinning, dystocia, retained
      placenta, and metritis after calving than cows without PVD. Count of
      polymorphonuclear leukocytes (PMNL) in uterine cytology 1, 2, and 7 d after
      intrauterine infusion was not statistically different among treatments. From d 0
      to 1, however, PMNL count in uterine cytology of PBS cows increased by 5%,
      whereas the PMNL count in uterine cytology of LPS150 and LPS300 cows increased by
      54 and 48%, respectively. Treatment did not affect the likelihood of cows being
      diagnosed with PVD 7 and 28 d after intrauterine infusion. Cows without PVD and
      LPS150 cows were more likely to be pregnant after the first postpartum AI than
      PBS cows. After the second postpartum AI, cows without PVD were more likely to be
      pregnant than PBS and LPS300 cows. Hazard of pregnancy up to 200 d postpartum was
      decreased for PBS and LPS300 cows compared with cows without PVD, and it tended
      to be decreased for LPS150 cows compared with cows without PVD. Intrauterine
      treatment with 150 ug of E. coli LPS of cows diagnosed with PVD improved
      likelihood of pregnancy after the first postpartum AI, but further research is
      needed to elucidate the mechanism by which LPS treatment improved fertility.

PMID- 28434753
TI  - Inform and consent: more than just "sign here".

PMID- 28434754
TI  - [Patient safety culture in Family practice residents of Galicia].
AB  - OBJECTIVE: To determine the views held by Family practice (FP) residents on the
      different dimensions of patient safety, in order to identify potential areas for
      improvement. DESIGN: A cross-sectional study. LOCATION: Seven FP of Galicia
      teaching units. PARTICIPANTS: 182 FP residents who completed the Medical Office
      Survey on Patient Safety Culture questionnaire. MEASUREMENTS: The Medical Office
      Survey on Patient Safety Culture questionnaire was chosen because it is
      translated, validated, and adapted to the Spanish model of Primary Care. The
      results were grouped into 12 composites assessed by the mentioned questionnaire.
      The study variables were the socio-demographic dimensions of the questionnaire,
      as well as occupational/professional variables: age, gender, year of residence,
      and teaching unit of FP of Galicia. RESULTS: The "Organisational learning" and
      "Teamwork" items were considered strong areas. However, the "Patient safety and
      quality issues", "Information exchange with other settings", and "Work pressure
      and pace" items were considered areas with significant potential for improvement.
      First-year residents obtained the best results and the fourth-year ones the
      worst. CONCLUSIONS: The results may indicate the need to include basic knowledge
      on patient safety in the teaching process of FP residents in order to increase
      and consolidate the fragile patient safety culture described in this study.

PMID- 28434755
TI  - [Evaluation of the operating results and costs associated with the implementation
      of a flexible ureteroscopy activity within a university hospital center].
AB  - INTRODUCTION: The increasing use of flexible ureteroscopy (USSR) sets the cost
      problems inevitably associated with the fragility of these endoscopes. The aim of
      this work is to clear from a recent example (universitary hospital) results,
      costs during the implementation of this technique. MATERIAL AND METHODS: This is
      a retrospective study conducted from December 2012 (date of introduction of the
      activity) in March 2015 concerning the USSR made in a French universitary
      hospital for stone disease. In this analysis, the cost of consumables was not
      evaluated, nor the costs of the operating theater or hospitalization. RESULTS:
      One hundred forty-one hundred and thirteen patients USSR were conducted by seven
      surgeons. Seventeen breakages and failures have been identified and have led to
      the sending of the endoscope for repair. Breakage rate and failure was 12%. All
      failures were treated with a standard exchange of the device (including 4
      standard exchanges made under warranty). The estimated average cost of outages
      was 3600 euros. This represents an average cost per procedure of about 625 euros
      (acquisition plus cost of failures) without counting the costs of sterilization
      or high-level disinfection. The impossibility of relocating the lower calyx
      stones is associated with an excess risk of breakage (odd ratio: 2.92 CI95:
      [1.02; 8.37]). CONCLUSION: This study is novel because it focuses on the cost of
      implementing a technique in a French university hospital. The use of flexible
      ureteroscope to unique uses might be an interesting source of savings in the
      implementation of this technique. This remains to be evaluated. LEVEL OF
      EVIDENCE: 5.

PMID- 28434756
TI  - Evaluation of tinnitus retraining therapy for patients with normal audiograms
      versus patients with hearing loss.
AB  - OBJECTIVE: A few chronic tinnitus patients show normal hearing thresholds in the
      pure tone audiometry from 125Hz to 8000Hz (<=20dB). We report the characteristics
      of the course of those patients underwent tinnitus retraining therapy (TRT)
      compared with other patients suffering from chronic and severe tinnitus. METHODS:
      We identified 13 patients with normal hearing thresholds among 242 patients
      suffering over 3 months, Tinnitus Handicap Inventory (THI) >=16/100, and follow
      up period is over 6 months. We divided into two groups - tinnitus with normal
      audiometry and with hearing loss - and contrasted these patients with age,
      gender, tinnitus duration, instruments for TRT, loudness and pitch of the
      tinnitus, THI and Visual Analogue Scale (VAS) scores. RESULTS: The pitch-match of
      the tinnitus was higher and tinnitus duration was shorter in normal audiometry.
      The age is younger and the tinnitus loudness was smaller in normal hearing group
      significantly. THI of normal audiogram group showed significant improvement on 18
      months treatment, though it once got worse on 12 months. THI of hearing loss
      group showed significant decreases in first 3 months and decreased slightly until
      48 months treatment. The VAS scores of annoyance also showed a large decrease in
      first 3 months and decreased slightly until 24 months. Both THI after 48 months
      and VAS scores after 24 months treatment showed almost stable until 72 months in
      hearing loss group. CONCLUSION: Chronic tinnitus with normal audiometry and with
      hearing loss both showed adaptation with TRT. Normal audiometry group with
      chronic tinnitus may have damage in high frequency though there were not
      significant differences between two groups as to tinnitus pitch-match. They also
      need at least 18 months TRT to become adaptation, while 48 months treatment is
      enough and first 3 months treatment is very important for hearing loss with
      chronic tinnitus.

PMID- 28434757
TI  - Unusual Kissing Lesions: Lessons From Rural Tanzania.

PMID- 28434758
TI  - Mallards (Anas platyrhynchos) and wastewater ponds, Part II: Developmental,
      physiological, morphological and behavioural effects of ingestion of secondary
      clarified effluent water.
AB  - Rather than migrating, mallard ducks may choose to overwinter in northern cities
      on open-water thermal refuges, such as municipal wastewater treatment ponds,
      which in Edmonton, Canada, stay >=10 degrees C during frigid winter months.
      Refuging mallards spend appreciable time daily on these ponds and hydrate using
      secondary clarified municipal wastewater (SCEW). We aimed to determine if SCEW
      ingestion affected mallard health. To this end, we gavaged newly hatched mallards
      (domesticated Pekin strain) over their first month with SCEW, as well as water
      representing negative and positive controls (municipal tap water, and the primary
      active ingredient from birth control pills, 17alpha-ethinyl estradiol (EE2),
      respectively). The gavage of SCEW did not affect mass of the body, liver, spleen
      or heart, but was associated with small increases in beak and wing chord length.
      In the positive control, EE2 gavage caused similar responses, but also increased
      tarsus and phallus length. The increases likely owed to the stimulatory effects
      of estrogenic substances on bone and phallus development. For the
      biotransformation enzyme CYP2H1, gene expression was numerically increased by
      both SCEW and EE2. In terms of behavior, SCEW and EE2 gavage reduced two
      infrequently detected behaviours, pecking and resting alone. Our results suggest
      that SCEW ingestion would be unlikely to cause any overt health effects in
      adults, but may evoke subtle, covert effects nevertheless.

PMID- 28434759
TI  - Corrigendum to "Ecotoxicity study of titania (TiO2) NPs on two microalgae
      species: Scenedesmus sp. and Chlorella sp." [Ecotoxicol. Environ. Saf. 74/5
      (2011) 1180-1187].

PMID- 28434760
TI  - Omega-3 Fatty Acid Supplementation is Associated With Oxidative Stress and
      Dyslipidemia, but Does not Contribute to Better Lipid and Oxidative Status on
      Hemodialysis Patients.
AB  - OBJECTIVE: The aim of the study was to explore the effects of n-3 polyunsaturated
      fatty acids (PUFA) supplementation in physiological doses on oxidative stress
      (OS) and dyslipidemia in patients on hemodialysis (HD). DESIGN AND METHODS:
      Randomized, double-blind, controlled, experimental trial. A total of 88 HD
      patients >=18 years old and on HD for at least 6 months. A total of 43 patients
      received 1.28 g/day of n-3 PUFA, and 45 other patients received soybean oil for
      12 weeks. Both oil supplements were vitamin E standardized. Routine tests, lipid
      profile, advanced oxidation protein products, isoprostanes, vitamins C and E,
      total antioxidant capacity, serum fatty acids, and adverse effects were
      evaluated. RESULTS: Supplementation was not able to alter lipid or OS profiles.
      There was an increase in the serum n-3 PUFA levels (eicosapentaenoic acid: +116%;
      docosahexaenoic acid: +100%) and an improvement in the n-6/n-3 ratio (-49%) in
      the supplemented group. Associations between n-3 PUFA and improvement in
      isoprostane and advanced oxidation protein product and HDL were observed.
      Treatment was well tolerated. CONCLUSION: Although the n-3 PUFA supplementation
      was associated with lower concentrations of isoprostane and advanced oxidation
      protein product and higher HDL levels, it was not sufficient for the improvement
      of highly prevalent risk factors, such as OS and dyslipidemia in HD patients.

PMID- 28434761
TI  - Improvement in Nutritional Status in Patients With Chronic Kidney Disease-4 by a
      Nutrition Education Program With No Impact on Renal Function and Determined by
      Male Sex.
AB  - OBJECTIVE: Protein-energy wasting (PEW) is associated with increased morbidity
      and mortality and a rapid deterioration of kidney function in patients with
      chronic kidney disease (CKD). However, there is little information regarding the
      effect of nutrition intervention. The aims of this study were to evaluate the
      efficacy and safety of a nutrition education program (NEP) in patients with
      nondialysis dependent CKD (NDD-CKD), based on the diagnostic criteria for PEW
      proposed by the International Society of Renal Nutrition and Metabolism. The
      design of the study was a 6-month longitudinal, prospective, and interventional
      study. The study was conducted from March 2008 to September 2011 in the
      Nephrology Department of La Paz University Hospital in Madrid, Spain. SUBJECTS: A
      total of 160 patients with NDD-CKD started the NEP, and 128 finished it.
      INTERVENTION: The 6-month NEP consisted of designing an individualized diet plan
      based on the patient's initial nutritional status, and 4 nutrition education
      sessions. MAIN OUTCOME MEASURES: Changes in nutritional status (PEW) and
      biochemical, anthropometric and body composition parameters. RESULTS: After 6
      months of intervention, potassium and inflammation levels decreased, and an
      improved lipid profile was found. Body mass index lowered, with increased muscle
      mass and a stable fat mass. Men showed increased levels of albumin and
      prealbumin, and women showed decreased proteinuria levels. The prevalence of PEW
      decreased globally (27.3%-10.9%; P = .000), but differently in men (29.5%-6.5%; P
      = .000) and in women (25.4%-14.9%; P = .070), 3 of the women having worsened.
      Kidney function was preserved, despite increased protein intake. CONCLUSION: The
      NEP in NDD-CKD generally improved nutritional status as measured by PEW
      parameters, but individual poorer results indicated the need to pay special
      attention to female sex and low body mass index at the start of the program.

PMID- 28434762
TI  - Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one derivatives
      containing thiourea and acylthiourea against Meloidogyne incognita.
AB  - Two series of novel 1,2,3-benzotriazin-4-one derivatives containing thiourea and
      acylthiourea were designed and synthesized. The bioassay results showed that most
      of the test compounds showed good nematicidal activity against M. incognita at
      the concentration of 10.0mgL-1in vivo. The compounds A13, A17 and B3 showed
      excellent nematicidal activity on the second stage juveniles of the root-knot
      nematode with the inhibition rate of 51.3%, 58.3% and 51.3% at the concentration
      of 1.0mgL-1 respectively. It suggested that the structure of 1,2,3-benzotriazin-4
      one derivatives containing thiourea and acylthiourea could be optimized further.

PMID- 28434764
TI  - Novel non-trimethoxylphenyl piperlongumine derivatives selectively kill cancer
      cells.
AB  - Piperlongumine (PL) is a natural alkaloid with broad biological activities.
      Twelve analogues have been designed and synthesized with non-substituted benzyl
      rings or heterocycles in this work. Most of the compounds showed better
      anticancer activities than the parent PL without apparent toxicity in normal
      cells. Elevation of cellular ROS levels was one of the main anticancer mechanisms
      of these compounds. Cell apoptosis and cell cycle arrest for the best compound
      ZM90 were evaluated and similar mechanism of action with PL was demonstrated. The
      SAR was also characterized, providing worthy directions for further optimization
      of PL compounds.

PMID- 28434763
TI  - Computer-aided discovery of two novel chalcone-like compounds active and
      selective against Leishmania infantum.
AB  - Leishmaniasis are infectious diseases caused by parasites of genus Leishmania
      that affect affects 12 million people in 98 countries mainly in Africa, Asia, and
      Latin America. Effective treatments for this disease are urgently needed. In this
      study, we present a computer-aided approach to investigate a set of 32 recently
      synthesized chalcone and chalcone-like compounds to act as antileishmanial
      agents. As a result, nine most promising compounds and three potentially inactive
      compounds were experimentally evaluated against Leishmania infantum amastigotes
      and mammalian cells. Four compounds exhibited EC50 in the range of 6.2-10.98MUM.
      In addition, two compounds, LabMol-65 and LabMol-73, exhibited cytotoxicity in
      macrophages >50MUM that resulted in better selectivity compared to standard drug
      amphotericin B. These two compounds also demonstrated low cytotoxicity and high
      selectivity towards Vero cells. The results of target fishing followed by
      homology modeling and docking studies suggest that these chalcone compounds could
      act in Leishmania because of their interaction with cysteine proteases, such as
      procathepsin L. Finally, we have provided structural recommendations for
      designing new antileishmanial chalcones.

PMID- 28434765
TI  - 4-Connected azabicyclo[5.3.0]decane Smac mimetics-Zn2+ chelators as dual action
      antitumoral agents.
AB  - Putative dual action compounds (DACs 3a-d) based on azabicyclo[5.3.0]decane (ABD)
      Smac mimetic scaffolds linked to Zn2+-chelating 2,2'-dipicolylamine (DPA) through
      their 4 position are reported and characterized. Their synthesis, their target
      affinity (cIAP1 BIR3, Zn2+) in cell-free assays, their pro-apoptotic effects, and
      their cytotoxicity in tumor cells with varying sensitivity to Smac mimetics are
      described. A limited influence of Zn2+ chelation on in vitro activity of DPA
      substituted DACs 3a-d was sometimes perceivable, but did not lead to strong
      cellular synergistic effects. In particular, the linker connecting DPA with the
      ABD scaffold seems to influence cellular Zn2+-chelation, with longer lipophilic
      linkers/DAC 3c being the optimal choice.

PMID- 28434766
TI  - Stereoselective synthesis of enantiopure N-substituted pyrrolidin-2,5-dione
      derivatives by 1,3-dipolar cycloaddition and assessment of their in vitro
      antioxidant and antibacterial activities.
AB  - 1,3-Dipolar cycloaddition between a chiral nitrone and N-substituted maleimides
      afforded unprecedented enantiopure spiro-fused heterocycles in good yields with a
      high enantio- and diastereoselectivity. The reaction was taking place on the less
      hindered face of the nitrone. The obtaining heterocycles were screened for their
      in vitro antioxidant properties and the results revealed that the potent
      antioxidant activity was generally recorded to compounds (3g) and (3e). The in
      vitro antibacterial activities of these two compounds were also investigated and
      the results demonstrated the strongest potential of compound (3g) against all the
      tested bacteria. Molecular properties were analyzed and showed good oral drug
      candidate like properties and that could be exploited as a potential antioxidant
      and antimicrobial agent. Finally, the preliminary results obtained from this
      investigation attempted to clarify if the structurally different side chains of
      active compounds interfere with their biological properties.

PMID- 28434767
TI  - Extrarenal rhabdoid tumor presented with an immobile arm in a one-year-old boy.
AB  - Infants with an immobile arm may be easily overlooked in primary care settings.
      Differential diagnoses include injuries, infections, neuropathies, ischemia and
      rarely, neoplasms. We report the case of a one-year-old boy with weakness in his
      left arm after minor trauma with a diagnosis of brachial plexus palsy initially.
      After rehabilitation for 2months, his weakness progressed to unsteady gait and
      quadriparesis. MRI revealed a huge solid tumor in the left supraclavicular fossa,
      which also involved the left brachial plexus, upper thoracic cavity, and left
      paravertebral space with invasion into the spinal canal. Microscopically, the
      medium-large polygonal tumor cells had an eccentric eosinophilic cytoplasm and
      immunostaining showed a loss of nuclear INI1 expression. Array comparative
      genomic hybridization of the tumor tissue confirmed a segmental deletion at
      chromosome region 22q11.23 involving the SMARCB1 gene. The final diagnosis was
      cervical paravertebral malignant rhabdoid tumor with intraspinal epidural and
      intradural invasion, a rare case of extrarenal extracranial rhabdoid tumor
      (ERRT). The intraspinal part of the tumor was resected followed by interval
      compressed chemotherapy with vincristine-doxorubicin-cyclophosphamide alternating
      with ifosfamide-etoposide (VDC/IE). The tumor showed very good partial response
      to four cycles of chemotherapy with gradual recovery of neurological symptoms.
      ERRT is a very rare and aggressive tumor that mainly occurs in infants and
      children and may manifest with vague neurological symptoms when it involves the
      spinal cord and/or peripheral nerves. A neoplasm such as ERRT originating from or
      involving the brachial plexus should be considered in the differential diagnosis
      of an immobile arm in infancy.

PMID- 28434768
TI  - Restless legs syndrome in adolescents.

PMID- 28434769
TI  - Kleine-Levin syndrome; An update and mini-review.
AB  - Since 1962, when Critchley and Hoffman coined the term Kleine-Levin Syndrome
      (KLS) for the triad of hypersomnia, excessive eating and "often abnormal
      behavior" which they have observed in 11 adolescent boys, the number of patients
      recognized with this rare syndrome expanded, the spectrum of the clinical
      presentation, disease course, prognosis, gender specificity and the presence of
      familial cases were established. However, in spite of the progress made in
      neuroscience, the search for the cause, neuroanatomy, pathophysiology and drug
      treatment of KLS is still ongoing. In this mini-review we will describe in some
      detail the scientific efforts made to understand in depth the complex
      symptomatology of KLS and refer also to updated findings reached up till now.

PMID- 28434770
TI  - Acute pulmonary edema associated with ketamine use in a patient with coronary
      artery disease.

PMID- 28434772
TI  - Neurointerventional staffing: The next frontier.

PMID- 28434771
TI  - Pharmacological management of cerebral venous sinus thrombosis with full-dose IV
      heparin infusion and its clinical outcomes.
AB  - OBJECTIVE: To report a case of successful use of unfractionated heparin (UFH)
      infusion to treat cerebral venous sinus thrombosis (CVST). CASE SUMMARY: A 54
      year-old female with a history of ovarian cancer addressed through palliative
      care, presents to the Emergency Department complaining of nausea, vomiting and
      headache for the last 72h. The patient was on a home regimen of enoxaparin
      1.5mg/kg subcutaneously daily for recent pulmonary embolism and deep vein
      thrombosis that developed while on warfarin therapy previously. CT scan showed
      superior sagittal sinus thrombosis. UFH infusion was initiated and continued for
      48h until the headache dissipated. DISCUSSION: Stable CVST may be treated with
      UFH infusion; however, there is limited literature that describes UFH dosing for
      CVST management. CONCLUSIONS: UFH may be considered as one of the pharmacological
      agents to manage CVST. The dosing for UFH bolus and infusion is similar to
      treatment dose for pulmonary embolism/deep vein thrombosis management with goal
      anti-Xa between 0.3 and 0.7units/mL.

PMID- 28434773
TI  - mStroke: "Mobile Stroke"-Improving Acute Stroke Care with Smartphone Technology.
AB  - OBJECTIVE: This study aimed to evaluate the effect of method and time of system
      activation on clinical metrics in cases utilizing the Stop Stroke (Pulsara, Inc.)
      mobile acute stroke care coordination application. METHODS: A retrospective
      cohort analysis of stroke codes at 12 medical centers using Stop Stroke from
      March 2013 to May 2016 was performed. Comparison of metrics (door-to-needle time
      [DTN] and door-to-CT time [DTC], and rate of DTN <= 60 minutes [goal DTN]) was
      performed between subgroups based on method (emergency medical service [EMS]
      versus emergency department [ED]) and time of activation. Effects were adjusted
      for confounders (age, sex, National Institutes of Health Stroke Scale [NIHSS]
      score) using multiple linear and logistic regression. RESULTS: The final dataset
      included 2589 cases. Cases activated by EMS were more severe (median NIHSS score
      8 versus 4, P < .0001) and more likely to receive recombinant tissue plasminogen
      activator (20% versus 12%, P < .0001) than those with ED activation. After
      adjustment, cases with EMS activation had shorter DTC (6.1 minutes shorter, 95%
      CI [-10.3, -2]) and DTN (12.8 minutes shorter, 95% CI [-21, -4.6]) and were more
      likely to meet goal DTN (OR 1.83, 95% CI [1.1, 3]). Cases between 1200 and 1800
      had longer DTC (7.7 minutes longer, 95% CI [2.4, 13]) and DTN (21.1 minutes
      longer, 95% CI [9.3, 33]), and reduced rate of goal DTN (OR .3, 95% CI [.15,
      .61]) compared to those between 0000 and 0600. CONCLUSIONS: Incorporating real
      time prehospital data obtained via smartphone technology provides unique insight
      into acute stroke codes. Activation of mobile electronic stroke coordination in
      the field appears to promote a more expedited and successful care process.

PMID- 28434774
TI  - Myocardial Infarction Following Intravenous Thrombolysis for Acute Ischemic
      Stroke: Case Report and Literature Review.
AB  - Embolic complications of intravenous thrombolysis for acute ischemic stroke are
      increasingly recognized, and to date several cases of myocardial infarction soon
      after the administration of alteplase have been reported. We describe a case of
      early anterior myocardial infarction during intravenous thrombolysis for stroke
      and review the current literature.

PMID- 28434775
TI  - Ibague Saludable: A novel tool of Information and Communication Technologies for
      surveillance, prevention and control of dengue, chikungunya, Zika and other
      vector-borne diseases in Colombia.

PMID- 28434776
TI  - A patient who made an impact on how I practice: Severe leptospirosis presenting
      as ARDS in the ICU.
AB  - Severe leptospirosis can be a rare cause of acute respiratory distress syndrome
      (ARDS) and multiorgan failure. A patient who made an impact on how I practice was
      a case of severe leptospirosis (Weil's disease) that presented as ARDS in the
      ICU. Leptospirosis is an under-reported infectious disease worldwide and should
      be considered as a cause of ARDS especially in patients with exposure history
      complicated with diffuse alveolar bleeding (DAH), icteric hepatitis and renal
      deterioration. Empiric treatment should be recommended before confirmation of
      laboratory tests as serological diagnosis is time consuming.

PMID- 28434777
TI  - The heat shock protein 60 promotes progesterone synthesis in mitochondria of JEG
      3 cells.
AB  - Progesterone synthesis in human placenta is essential to maintain pregnancy. The
      limiting step in placental progesterone synthesis is cholesterol transport from
      the cytoplasm to the inner mitochondrial membrane. Multiple proteins located in
      mitochondrial contact sites seem to play a key role in this process. Previously,
      our group identified the heat shock protein 60 (HSP60) as part of mitochondrial
      contact sites in human placenta, suggesting its participation in progesterone
      synthesis. Here, we examined the role of HSP60 in progesterone synthesis. Our
      results show that over-expression of HSP60 in human placental choriocarcinoma
      cells (JEG-3) and human embryonic kidney 293 cells (HEK293) promotes progesterone
      synthesis. Furthermore, incubation of the HSP60 recombinant protein with intact
      isolated mitochondria from JEG-3 cells also promotes progesterone synthesis in a
      dose-related fashion. We also show that HSP60 interacts with STARD3 and P450scc
      proteins from mitochondrial membrane contact sites. Finally, we show that the
      HSP60 recombinant protein binds cholesterol. Ours results demonstrate that HSP60
      participates in mitochondrial progesterone synthesis. These findings provide
      novel insights into progesterone synthesis in the human placenta and its role in
      maintaining pregnancy.

PMID- 28434778
TI  - Live birth potential of good morphology and vitrified blastocysts presenting
      abnormal cell divisions.
AB  - This study included 238 good morphology blastocysts, which were transferred after
      vitrification-warming to 152 women by single blastocyst transfer in Holbaek
      Fertility Clinic, Denmark. Time-lapse recordings of transferred good morphology
      blastocysts were reassessed to recognize every abnormal cell division (ACD) from
      the 1st to the 4th cell cycle. ACDs were distinguished as failed cell divisions
      and multi-cell divisions. ACDs were recognized in 37.0% (no. 88/238) of good
      morphology blastocysts that were vitrified-warmed and transferred in our clinic.
      Good morphology blastocysts with ACDs showed a lower live birth rate (17.0%) than
      blastocyst with solely regular cell divisions (29.3%). ACDs could occur at more
      than one cell division in the same good morphology blastocyst. Reported as
      independent events, we observed ACDs occurring more frequently at the later cell
      cycles (1st: 1.3%; 2nd: 8.0%; 3rd: 18.5%; 4th: 18.1%). More blastocysts presented
      failed cell divisions (no. 95) than multi-cell divisions (no. 14). Live births
      were achieved from blastocysts showing multi-cell divisions at any cell cycle and
      failed cell divisions from the 2nd cell cycle. Analyses of the subgroup of first
      blastocyst transferred to each patient showed similar to results. In conclusion,
      good morphology blastocysts presenting ACDs can result in live birth although
      lower compared to blastocysts with solely regular cell division. Pre-implantation
      embryos in vitro may undergo self-selection or correcting processes. This
      supports the transfer of blastocysts instead of cleavage stage embryos, giving
      first priority to blastocyst showing solely regular cell divisions, and giving
      second priority to blastocysts presenting ACDs at any cell cycle.

PMID- 28434779
TI  - A comparative study of Cutibacterium (Propionibacterium) acnes clones from acne
      patients and healthy controls.
AB  - BACKGROUND: Cutibacterium (Propionibacterium) acnes is assumed to play an
      important role in the pathogenesis of acne. OBJECTIVES: To examine if clones with
      distinct virulence properties are associated with acne. METHODS: Multiple C.
      acnes isolates from follicles and surface skin of patients with moderate to
      severe acne and healthy controls were characterized by multilocus sequence
      typing. To determine if CC18 isolates from acne patients differ from those of
      controls in the possession of virulence genes or lack of genes conducive to a
      harmonious coexistence the full genomes of dominating CC18 follicular clones from
      six patients and five controls were sequenced. RESULTS: Individuals carried one
      to ten clones simultaneously. The dominating C. acnes clones in follicles from
      acne patients were exclusively from the phylogenetic clade I-1a and all belonged
      to clonal complex CC18 with the exception of one patient dominated by the
      worldwide-disseminated and often antibiotic resistant clone ST3. The clonal
      composition of healthy follicles showed a more heterogeneous pattern with
      follicles dominated by clones representing the phylogenetic clades I-1a, I-1b, I
      2 and II. Comparison of follicular CC18 gene contents, allelic versions of
      putative virulence genes and their promoter regions, and 54 variable-length
      intragenic and inter-genic homopolymeric tracts showed extensive conservation and
      no difference associated with the clinical origin of isolates. CONCLUSIONS: The
      study supports that C. acnes strains from clonal complex CC18 and the often
      antibiotic resistant clone ST3 are associated with acne and suggests that
      susceptibility of the host rather than differences within these clones may
      determine the clinical outcome of colonization.

PMID- 28434780
TI  - Total chemical synthesis of methylated analogues of histone 3 revealed KDM4D as a
      potential regulator of H3K79me3.
AB  - Histone H3 methylation plays an important role in regulating gene expression. In
      histones in general, this mark is dynamically regulated via various demethylases,
      which found to control cell fate decisions as well as linked to several diseases,
      including neurological and cancer. Despite major progress in studying methylation
      mark at various positions in H3 histone proteins, less is known about the
      regulation of methylated H3 at Lys79. Methylation at this site is known to have
      direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and
      34, as well as with acetylated H3 at Lys9. Herein we applied convergent total
      chemical protein synthesis to prepare trimethylated H3 at Lys79 to perform
      initial studies related to the regulation of this mark. Our study enabled us to
      identify KDM4D lysine demethylase as a potential regulator for trimethylated H3
      at Lys79.

PMID- 28434781
TI  - Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2
      P3 ligands: Synthesis, biological evaluation and X-ray structural studies of
      inhibitor-HIV-1 protease complex.
AB  - Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1
      protease complexes, we have designed a series of isophthalamide-derived
      inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines
      as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound
      4b has shown an enzyme Ki of 0.025nM and antiviral IC50 of 69nM. An X-ray crystal
      structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33A
      resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at
      1.27A resolution. These structures revealed important molecular insight into the
      inhibitor-HIV-1 protease interactions in the active site.

PMID- 28434783
TI  - Electron ptychographic phase imaging of light elements in crystalline materials
      using Wigner distribution deconvolution.
AB  - Recent development in fast pixelated detector technology has allowed a two
      dimensional diffraction pattern to be recorded at every probe position of a two
      dimensional raster scan in a scanning transmission electron microscope (STEM),
      forming an information-rich four dimensional (4D) dataset. Electron ptychography
      has been shown to enable efficient coherent phase imaging of weakly scattering
      objects from a 4D dataset recorded using a focused electron probe, which is
      optimised for simultaneous incoherent Z-contrast imaging and spectroscopy in
      STEM. Therefore coherent phase contrast and incoherent Z-contrast imaging modes
      can be efficiently combined to provide a good sensitivity of both light and heavy
      elements at atomic resolution. In this work, we explore the application of
      electron ptychography for atomic resolution imaging of strongly scattering
      crystalline specimens, and present experiments on imaging crystalline specimens
      including samples containing defects, under dynamical channelling conditions
      using an aberration corrected microscope. A ptychographic reconstruction method
      called Wigner distribution deconvolution (WDD) was implemented. Experimental
      results and simulation results suggest that ptychography provides a readily
      interpretable phase image and great sensitivity for imaging light elements at
      atomic resolution in relatively thin crystalline materials.

PMID- 28434782
TI  - Dimeric isoxazolyl-1,4-dihydropyridines have enhanced binding at the multi-drug
      resistance transporter.
AB  - A series of dimeric isoxazolyl-1,4-dihydropyridines (IDHPs) were prepared by
      click chemistry and examined for their ability to bind the multi-drug resistance
      transporter (MDR-1), a member of the ATP-binding cassette superfamily (ABC).
      Eight compounds in the present study exhibited single digit micromolar binding to
      this efflux transporter. One monomeric IDHP m-Br-1c, possessed submicromolar
      binding of 510nM at MDR-1. Three of the dimeric IDHPs possessed <1.5uM activity,
      and 4b and 4c were observed to have superior binding selectivity compared to
      their corresponding monomers verses the voltage gated calcium channel (VGCC). The
      dimer with the best combination of activity and selectivity for MDR-1 was analog
      4c containing an m-Br phenyl moiety in the 3-position of the isoxazole, and a
      tether with five ethyleneoxy units, referred to herein as Isoxaquidar. Two
      important controls, mono-triazole 5 and pyridine 6, also were examined,
      indicating that the triazole - incorporated as part of the click assembly as a
      spacer - contributes to MDR-1 binding. Compounds were also assayed at the
      allosteric site of the mGluR5 receptor, as a GPCR 7TM control, indicating that
      the p-Br IDHPs 4d, 4e and 4f with tethers of from n=2 to 5 ethylenedioxy units,
      had sub-micromolar affinities with 4d being the most efficacious at 193nM at
      mGluR5. The results are interpreted using a docking study using a human ABC as
      our current working hypothesis, and suggest that the distinct SARs emerging for
      these three divergent classes of biomolecular targets may be tunable, and
      amenable to the development of further selectivity.

PMID- 28434784
TI  - Perspectives on in situ electron microscopy.
AB  - In situ transmission electron microscopy (TEM) with the ability to reveal
      materials dynamic processes with high spatial and temporal resolution has
      attracted significant interest. The recent advances in in situ methods, including
      liquid and gas sample environment, pump-probe ultrafast microscopy, nanomechanics
      and ferroelectric domain switching the aberration corrected electron optics as
      well as fast electron detector has opened new opportunities to extend the impact
      of in situ TEM in broad areas of research ranging from materials science to
      chemistry, physics and biology. In this article, we highlight the development of
      liquid environment electron microscopy and its applications in the study of
      colloidal nanoparticle growth, electrochemical processes and others; in situ
      study of topological vortices in ferroelectric and ferromagnetic materials. At
      the end, perspectives of future in situ TEM are provided.

PMID- 28434785
TI  - Significant gastric distension caused by superior mesenteric artery syndrome or
      Wilkie's syndrome.

PMID- 28434786
TI  - Laparoscopic sleeve gastrectomy after failed gastric banding: is it really
      effective? Six years of follow-up.

PMID- 28434787
TI  - Integrated ecotechnology approach towards treatment of complex wastewater with
      simultaneous bioenergy production.
AB  - Sequential integration of three stage diverse biological processes was studied by
      exploiting the individual process advantage towards enhanced treatment of complex
      chemical based wastewater. A successful attempt to integrate sequence batch
      reactor (SBR) with bioelectrochemical treatment (BET) and finally with microalgae
      treatment was studied. The sequential integration has showed individual substrate
      degradation (COD) of 55% in SBR, 49% in BET and 56% in microalgae, accounting for
      a consolidated treatment efficiency of 90%. Nitrates removal efficiency of 25%
      was observed in SBR, 31% in BET and 44% in microalgae, with a total efficiency of
      72%. The SBR treated effluents fed to BET with the electrode intervention showed
      TDS removal. BET exhibited relatively higher process performance than SBR. The
      integration approach significantly overcame the individual process limitations
      along with value addition as biomass (1.75g/L), carbohydrates (640mg/g), lipids
      (15%) and bioelectricity. The study resulted in providing a strategy of combining
      SBR as pretreatment step to BET process and finally polishing with microalgae
      cultivation achieving the benefits of enhanced wastewater treatment along with
      value addition.

PMID- 28434788
TI  - Bicarbonate-based cultivation of Dunaliella salina for enhancing carbon
      utilization efficiency.
AB  - In this study, bicarbonate was proposed as an alternative carbon source to
      overcome exceedingly low CO2 fixation efficiency of conventional microalgae
      cultivation system. 5gL-1 of sodium bicarbonate was found to well support the
      growth of Dunaliella salina, showing 2.84-fold higher specific growth rate than a
      bicarbonate-free control. This bicarbonate-fed cultivation also could yield
      biomass productivity similar to that of CO2-based system as long as pH was
      controlled. While the supplied CO2, because of its being a gas, was mostly lost
      and only 3.59% of it was used for biomass synthesis, bicarbonate was effectively
      incorporated into the biomass with 91.40% of carbon utilization efficiency. This
      study showed that the bicarbonate-based microalgae cultivation is indeed
      possible, and can even become a truly environment-friendly and workable approach,
      provided that a CO2 mineralization technology is concomitantly established.

PMID- 28434789
TI  - Conversion of biomass to hydroxymethylfurfural: A review of catalytic systems and
      underlying mechanisms.
AB  - Conversion of biomass waste to hydroxymethylfurfural (HMF), a value-added
      platform chemical, has captured great research interests driven by the economic
      and environmental incentives. This review evaluates the recent development of
      biomass conversion systems for high HMF yield and selectivity, with a focus on
      the performance of emerging catalysts and solvents from a mechanistic view. We
      highlight that the ratio and strength of Bronsted and Lewis acid in bifunctional
      catalyst are critical for maximizing HMF production by selective improvement in
      the kinetics of desirable reactions (hydrolysis, isomerization, and dehydration)
      over undesirable reactions (rehydration, polymerization). The characteristics of
      solvent mixture such as functional groups and speciation govern the reactivity of
      substrate towards desirable reactions and stability of HMF and intermediates
      against side reactions. Research efforts to unravel the interactions among co
      catalysts/co-solvents and between catalysts and solvents are encouraged, thereby
      engineering a synergistic conversion system for biomass valorization.

PMID- 28434790
TI  - Short N-terminal galanin fragments are occurring naturally in vivo.
AB  - : The galanin family currently consists of four peptides, namely galanin, galanin
      message associated peptide, galanin-like peptide and alarin. Unlike galanin that
      signals through three different G protein-coupled receptors; GAL1, GAL2, and
      GAL3, binding at its N-terminal end, the cognate receptors for other members of
      the galanin family are currently unknown. Research using short N-terminal galanin
      fragments generated either by enzymatic cleavage or solid-phase synthesis has
      revealed differences in their receptor binding properties exerting numerous
      biological effects distinct from galanin(1-29) itself. Our studies on tissue
      extracts derived from rat small intestine and bovine gut using chromatographic
      techniques and sensitive galanin(1-16)-specific radioimmunoassay revealed the
      presence of immunoreactive compounds reacting with antiserum against galanin(1
      16) distributed in distinct elution volumes. These results suggested a possible
      presence of short N-terminal galanin fragments also in vivo. Moreover, employing
      immunoaffinity chromatography and reverse-phase high performance liquid
      chromatography (HPLC) followed by mass spectrometry allowed specific enrichment
      of these immunoreactive compounds from rat tissues and identification of their
      molecular structure. Indeed, our study revealed presence of several distinct
      short N-terminal galanin sequences in rat tissue. To prove their receptor
      binding, four of the identified sequences were synthetized, namely, galanin(1
      13), galanin(1-16), galanin(1-20), galanin(6-20), and tested on coronal rat brain
      sections competing with 125I-labeled galanin(1-29). Our autoradiographs confirmed
      that galanin(1-13), galanin(1-16), and galanin(1-20) comprehensively displaced
      125I-galanin(1-29) but galanin(6-20) did not. Here we show, for the first time,
      that short N-terminal galanin fragments occur naturally in rat tissues and that
      similar or identical galanin sequences can be present also in tissues of other
      species. BIOLOGICAL SIGNIFICANCE: This study is first to provide an evidence of
      the presence of short N-terminal galanin fragments in vivo in a biological system
      and provides further foundations for the previous studies using synthetized short
      N-terminal galanin fragments.

PMID- 28434791
TI  - Neuronal cells derived from human induced pluripotent stem cells as a functional
      tool of melanocortin system.
AB  - BACKGROUND: The preparation of human neurons derived from human induced
      pluripotent stem (iPS) cells can serve as a potential tool for evaluating the
      physiological and pathophysiological properties of human neurons and for drug
      development. METHODS: In the present study, the functional activity in neuronal
      cells differentiated from human iPS cells was observed. RESULTS: The
      differentiated cells expressed mRNAs for classical neuronal markers (microtubule
      associated protein 2, beta-tubulin III, calbindin 1, synaptophysin and
      postsynaptic density protein 95) and for subunits of various excitatory and
      inhibitory transmitters (NR1, NR2A, NR2B, GABAA alpha1). Moreover, the
      differentiated cells expressed neuropeptides and receptors which are
      predominantly present in the hypothalamus. The expression of mRNA for
      preopiomelanocortin, agouti-related protein (AgRP), melanocortin-3 receptor
      (MC3R) and melanocortin-4 receptor (MC4R) increased in culture with a peak on Day
      30 which subsequently decreased at Day 45. Immunoreactivities for MC3R and MC4R
      were also observed in cells differentiated from human iPS cells. Application of a
      potent agonist for MC3R and MC4R, [Nle4, D-Phe7]-alpha-melanocyte-stimulating
      hormone, significantly increased intracellular cAMP levels, but this was
      suppressed by AgRP (83-132) and SHU9119. CONCLUSIONS: These findings offer the
      possibility for drug developments using neurons differentiated from normal or
      disease-associated human iPS cells.

PMID- 28434793
TI  - Reflections on a life in epilepsy. Evolution of epileptology in Australia: Early
      days.

PMID- 28434792
TI  - Cloning and expression patterns of neuromedin U and its receptors in pigs.
AB  - Neuromedin U (NMU) is a highly conserved neuropeptide that performs a variety of
      physiological functions in animals via neuromedin U receptor-1 (NMUR1) and
      neuromedin U receptor-2 (NMUR2). In this study, we cloned the pig NMU, NMUR1 and
      NMUR2 genes. Bioinformatics analysis demonstrated that the pig NMU cDNA encoded
      the amino acids Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH2 at the C-terminus and that the
      NMU receptors, which are G-protein-coupled receptors (GPCRs), contained the seven
      transmembrane domains typical of GPCRs. Systemic NMU, NMUR1 and NMUR2 mRNA
      expression was investigated in various pig tissues using real-time RT-PCR. NMU
      mRNA was expressed both in the central nervous system (CNS) and in peripheral
      tissues. NMUR1 mRNA was widely expressed in peripheral tissues, whereas NMUR2
      mRNA was mainly expressed in the CNS. Immunohistochemistry (IHC) was used to
      determine the expression patterns of NMU and NMUR1, which were predominantly
      located in the gastrointestinal tract, genitourinary organs, and immune organs.
      This study presents molecular and morphological data to aid in additional NMU
      research in pigs.

PMID- 28434794
TI  - Behavioral and physiological responses of yellow perch (Perca flavescens) to
      moderate hypoxia.
AB  - While severe hypoxia can be lethal and is usually avoided by mobile aquatic
      organisms, moderate hypoxic conditions are likely more prevalent and may affect
      organisms, such as fishes, in a variety of systems. However, fishes have the
      potential to adjust physiologically and behaviorally and thus reduce the negative
      effects of hypoxia. Quantifying such physiological responses may shed light on
      the ability of fishes to tolerate reduced oxygen concentrations. This study
      assessed how two different hatchery populations of yellow perch Perca flavescens,
      a fish that is likely to encounter moderate hypoxic conditions in a variety of
      systems, responded to moderate hypoxic exposure through three experiments: 1) a
      behavioral foraging experiment, 2) an acute exposure experiment, and 3) a chronic
      exposure experiment. No marked behavioral or physiological adjustments were
      observed in response to hypoxia (e.g., hemoglobin, feeding rate, movement
      frequency, gene expression did not change to a significant degree), possibly
      indicating a high tolerance level in this species. This may allow yellow perch to
      utilize areas of moderate hypoxia to continue foraging while avoiding predators
      that may be more sensitive to moderately low oxygen.

PMID- 28434795
TI  - Near Eastern Plant Domestication: A History of Thought.
AB  - The Agricultural Revolution and plant domestication in the Near East (among its
      components) have fascinated generations of scholars. Here, we narrate the history
      of ideas underlying plant domestication research since the late 19th century.
      Biological and cultural perspectives are presented through two prevailing models:
      one views plant domestication as a protracted, unconscious evolutionary
      mutualistic (noncentric) process. The second advocates a punctuated, knowledge
      based human initiative (centric). We scrutinize the research landscape while
      assessing the underlying evolutionary and cultural mechanisms. A parsimony
      measure indicates that the punctuated-centric view better accords with
      archaeological records, and the geobotany and biology of the species, and
      requires fewer assumptions. The protracted alternative requires many assumptions,
      does not account for legume biology, fails to distinguish domestication from
      postdomestication changes, and, therefore, is less parsimonious.

PMID- 28434796
TI  - Incidence of urinary tract injury and utility of routine cystoscopy during total
      laparoscopic hysterectomy for endometrial cancer.

PMID- 28434797
TI  - Patterns of care survey: Radiotherapy for women with locally advanced cervical
      cancer.
AB  - BACKGROUND AND PURPOSE: Regarding latest developments, the need of a radiotherapy
      'Patterns of Care' survey was expressed by the Dutch National Platform
      Radiotherapy for Gynaecological Cancer (LPRGT). Therefore, this study
      investigated current practice for cervical cancer in all 16 radiation oncology
      centres in the Netherlands specialised in gynaecological oncology. MATERIAL AND
      METHODS: A structured 'patterns of care' questionnaire was completed and followed
      by an in-depth interview with radiation oncologists from all radiotherapy centres
      specialised in gynaecological oncology. Specific topics addressed were:
      definition of target volumes, treatment preparation, imaging for treatment
      planning, treatment planning, and image-guided adaptive radiotherapy for external
      beam radiotherapy and brachytherapy. RESULTS: Current radiotherapy practice in
      the Netherlands for cervical cancer appears to be in accordance with
      international standards. However, at the time of the survey some differences were
      revealed that might have relevant clinical impact. For instance: 1) Half of the
      centres acquired positron emission tomography combined with CT (PET-CT) for
      staging and target delineation for every patient, 2) The definition of upper
      border of the para-aortal lymph node area and dose prescription for external beam
      radiotherapy varied between the centres, and 3) 12 centres used a single
      treatment plan for delivering EBRT, and four used a plan-of-the-day strategy with
      a library of 3-4 treatment plans. CONCLUSIONS: Most differences were found at the
      cutting edge of clinical evidence. However, the majority of these uncertainties
      are topics being addressed in current and planned (inter)national studies.

PMID- 28434798
TI  - Prognostic value of dynamic hypoxia PET in head and neck cancer: Results from a
      planned interim analysis of a randomized phase II hypoxia-image guided dose
      escalation trial.
AB  - BACKGROUND AND PURPOSE: To prospectively assess the prognostic value of tumour
      hypoxia determined by dynamic [18F]Fluoromisonidazole (dynFMISO) PET/CT, and to
      evaluate both feasibility and toxicity in patients with locally advanced squamous
      cell carcinomas of the head and neck (LASCCHN) treated with dynFMISO image-guided
      dose escalation (DE) using dose-painting by contours. PATIENTS AND METHODS: We
      present a planned interim analysis of a randomized phase II trial. N=25 patients
      with LASCCHN received baseline dynFMISO PET/CT to derive hypoxic volumes (HV).
      Patients with tumour hypoxia were randomized into standard radiochemotherapy
      (stdRT) (70Gy/35 fractions) or DE (77Gy/35 fractions) to the HV. Patients with
      non-hypoxic tumours were treated with stdRT. Loco-regional control (LRC) in
      hypoxic patients randomized to stdRT was compared to non-hypoxic patients.
      Feasibility and toxicity were analysed for patients in the DE arm and compared to
      stdRT. RESULTS: With a mean follow-up of 27months, LRC in hypoxic patients
      receiving stdRT (n=10) was significantly worse compared to the non-hypoxic group
      (n=5) (2y-LRC 44.4% versus 100%, p=0.048). The respective LRC for the DE group
      (n=10) was 70.0%. Treatment compliance as well as acute and late toxicity did not
      show significant differences between the DE and the standard dose arms.
      CONCLUSION: Tumour hypoxia determined by baseline dynFMISO PET/CT is associated
      with a high risk of local failure in patients with LASCCHN. First data suggest
      that DE to HV is feasible without excess toxicity.

PMID- 28434799
TI  - Improved outcomes with dose escalation in localized prostate cancer treated with
      precision image-guided radiotherapy.
AB  - BACKGROUND AND PURPOSE: Dose-escalated radiotherapy (DE) improves outcomes in
      localized prostate cancer (PCa). The impact of DE in the context of image-guided
      radiotherapy (IGRT) remains unknown. Herein, we determined outcomes of three
      sequential cohorts treated with progressive DE-IGRT. MATERIALS AND METHODS: We
      analyzed data from 1998 to 2012. Patients treated with radical radiotherapy were
      included, with three sequential institutional schedules: (A) 75.6Gy, (B) 79.8Gy,
      (C) 78Gy, with 1.8, 1.9 and 2Gy/fraction, respectively. IGRT consisted of
      fiducial markers and daily EPID (A, B) or CBCT (C). RESULTS: 961 patients were
      included, with median follow-up of 6.1y. 30.5%, 32.6% and 36.9% were treated in
      A, B and C, respectively. Risk category distribution was 179 (18.6%) low-, 653
      (67.9%) intermediate- and 129 (13.5%) high-risk. PSA, T-category, androgen
      deprivation use and risk distribution were similar among groups. BCR (biochemical
      recurrence) was different (p<0.001) between A, B and C with 5-year rates of 23%,
      17% and 9%, respectively (HR 2.68 [95% CI 1.87-3.85] and 1.92 [95% CI 1.33-2.78]
      for A and B compared to C, respectively). Findings were most significant in the
      intermediate-risk category. Metastasis, cause-specific-death and toxicities were
      not different between cohorts. CONCLUSION: Our findings suggest continuous BCR
      improvement with progressive DE-IGRT. Prospective validation considering further
      DE with IGRT seems warranted.

PMID- 28434800
TI  - Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal
      Neurons.
AB  - Recent studies have shown that hippocampal "time cells" code for sequential
      moments in temporally organized experiences. However, it is currently unknown
      whether these temporal firing patterns critically rely on upstream cortical
      input. Here we employ an optogenetic approach to explore the effect of large
      scale inactivation of the medial entorhinal cortex on temporal, as well as
      spatial and object, coding by hippocampal CA1 neurons. Medial entorhinal
      inactivation produced a specific deficit in temporal coding in CA1 and resulted
      in significant impairment in memory across a temporal delay. In striking
      contrast, spatial and object coding remained intact. Further, we extended the
      scope of hippocampal phase precession to include object information relevant to
      memory and behavior. Overall, our work demonstrates that medial entorhinal
      activity plays an especially important role for CA1 in temporal coding and memory
      across time.

PMID- 28434801
TI  - Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for
      Axon Guidance in the Spinal Cord.
AB  - Netrin1 has been proposed to act from the floor plate (FP) as a long-range
      diffusible chemoattractant for commissural axons in the embryonic spinal cord.
      However, netrin1 mRNA and protein are also present in neural progenitors within
      the ventricular zone (VZ), raising the question of which source of netrin1
      promotes ventrally directed axon growth. Here, we use genetic approaches in mice
      to selectively remove netrin from different regions of the spinal cord. Our
      analyses show that the FP is not the source of netrin1 directing axons to the
      ventral midline, while local VZ-supplied netrin1 is required for this step.
      Furthermore, rather than being present in a gradient, netrin1 protein accumulates
      on the pial surface adjacent to the path of commissural axon extension. Thus,
      netrin1 does not act as a long-range secreted chemoattractant for commissural
      spinal axons but instead promotes ventrally directed axon outgrowth by
      haptotaxis, i.e., directed growth along an adhesive surface.

PMID- 28434802
TI  - Active Touch and Self-Motion Encoding by Merkel Cell-Associated Afferents.
AB  - Touch perception depends on integrating signals from multiple types of peripheral
      mechanoreceptors. Merkel-cell associated afferents are thought to play a major
      role in form perception by encoding surface features of touched objects. However,
      activity of Merkel afferents during active touch has not been directly measured.
      Here, we show that Merkel and unidentified slowly adapting afferents in the
      whisker system of behaving mice respond to both self-motion and active touch.
      Touch responses were dominated by sensitivity to bending moment (torque) at the
      base of the whisker and its rate of change and largely explained by a simple
      mechanical model. Self-motion responses encoded whisker position within a whisk
      cycle (phase), not absolute whisker angle, and arose from stresses reflecting
      whisker inertia and activity of specific muscles. Thus, Merkel afferents send to
      the brain multiplexed information about whisker position and surface features,
      suggesting that proprioception and touch converge at the earliest neural level.

PMID- 28434804
TI  - Nurses' knowledge and perception of delirium screening and assessment in the
      intensive care unit: Long-term effectiveness of an education-based knowledge
      translation intervention.
AB  - OBJECTIVES: To determine the impact of education on nurses' knowledge of
      delirium, knowledge and perception of a validated screening tool, and delirium
      screening in the ICU. METHODS: A quasi-experimental single group pretest-post
      test design. SETTING: A 16 bed ICU in a Canadian urban tertiary care centre. MAIN
      OUTCOME MEASURES: Nursing knowledge and perception were measured at baseline, 3
      month and 18-month periods. Delirium screening was then assessed over 24-months.
      RESULTS: During the study period, 197 surveys were returned; 84 at baseline, 53
      at 3-months post education, and 60 at the final assessment period 18-months post
      intervention. The significant improvements in mean knowledge scores at 3-months
      post intervention (7.2, SD 1.3) were not maintained at 18-months (5.3, SD 1.1).
      Screening tool perception scores remained unchanged. Improvements in the
      perception of utility were significant at both time periods (p=0.03, 0.02
      respectively). Physician value significantly improved at 18-months (p=0.01).
      Delirium screening frequency improved after education (p<0.001) demonstrating a
      positive correlation over time (p<0.01). CONCLUSION: Multifaceted education is
      effective in improving delirium knowledge and screening; however, without
      sustained effort, progress is transient. Education improved perceived tool
      utility and over time utility perception and physician value improved.

PMID- 28434805
TI  - Pressure ulcers in ICU patients: Incidence and clinical and epidemiological
      features: A multicenter study in southern Brazil.
AB  - OBJECTIVES: To evaluate the incidence and risk factors of pressure ulcers (PU) in
      adult patients admitted to intensive care units (ICUs), as well as the outcome
      (including ICU and hospital mortality) of these patients. METHODS:
      Epidemiological cohort multicenter prospective study, evaluating patients
      admitted for a period of 31days (June 01 to July 01, 2015) until hospital
      discharge. Epidemiological and clinical data were collected daily until ICU
      discharge, as was the incidence of PU, either new or present on admission.
      SETTING: 10 general adult ICUs. RESULTS: We evaluated 332 patients, 52.1% male,
      mean age 63.1 years. The most common cause of admission was medical diseases
      (50.3%), and the mean APACHE II score was 14.9. A total of 45 patients (13.6%)
      had PU; the most common sites were sacral, calcaneal, ears, and trochanter. The
      incidence of PU was related to predictive factors, such as the Braden Scale and
      length of lack of nutrition. The presence of PU was strongly related to
      unfavorable outcomes, such as Mechanical Ventilation (MV) duration and ICU and
      hospital mortality. CONCLUSIONS: PU incidence is related to severity of the
      patient's condition and predicted by Braden Scale score. The presence of PU is
      also related to adverse outcomes, such as MV duration and ICU and hospital
      mortality. It was also shown that patients with PU have a higher incidence of
      medical complications, such as acute renal failure, pneumonia, and the need for
      vasoactive drugs.

PMID- 28434803
TI  - Genetic dissection of the planarian reproductive system through characterization
      of Schmidtea mediterranea CPEB homologs.
AB  - Cytoplasmic polyadenylation is a mechanism of mRNA regulation prevalent in
      metazoan germ cells; it is largely dependent on Cytoplasmic Polyadenylation
      Element Binding proteins (CPEBs). Two CPEB homologs were identified in the
      planarian Schmidtea mediterranea. Smed-CPEB1 is expressed in ovaries and yolk
      glands of sexually mature planarians, and required for oocyte and yolk gland
      development. In contrast, Smed-CPEB2 is expressed in the testes and the central
      nervous system; its function is required for spermatogenesis as well as non
      autonomously for development of ovaries and accessory reproductive organs.
      Transcriptome analysis of CPEB knockdown animals uncovered a comprehensive
      collection of molecular markers for reproductive structures in S. mediterranea,
      including ovaries, testes, yolk glands, and the copulatory apparatus. Analysis by
      RNA interference revealed contributions for a dozen of these genes during
      oogenesis, spermatogenesis, or capsule formation. We also present evidence
      suggesting that Smed-CPEB2 promotes translation of Neuropeptide Y-8, a prohormone
      required for planarian sexual maturation. These findings provide mechanistic
      insight into potentially conserved processes of germ cell development, as well as
      events involved in capsule deposition by flatworms.

PMID- 28434806
TI  - Fibronectin-adherent peripheral blood derived mononuclear cells as Paclitaxel
      carriers for glioblastoma treatment: An in vitro study.
AB  - BACKGROUND: Glioblastoma (GBM) represents the most aggressive malignant brain
      tumor in adults, with a risible median life expectancy despite gold standard
      treatment. Novel drug-delivery methods have been explored. Here we evaluated the
      possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic
      lineage as drug-carrier. METHODS: MCs were obtained from 10 patients harboring a
      GBM, and from healthy volunteers, considered as controls. GBM tissue was also
      obtained from patients. MCs were cultured and the adherent population on
      fibronectin (FN-MCs), after immunocytochemistry and flow cytometry
      characterization, was loaded with Paclitaxel (FN-MCs-PTX). Antiproliferative and
      migration activity of FN-MCs-PTX was evaluated in two-dimensional (2D) and three
      dimensional (3D) co-culture assays with red fluorescent U87 Malignant Glioma
      cells and primary GBM cells. Antiangiogenic properties of FN-MCs-PTX were tested
      on cultures with endothelial cells. RESULTS: Phenotypical characterization showed
      a high expression of monocytic-dendritic markers in GBM cells and FN-MCs. FN-MCs
      demonstrated to effectively uptake PTX and to strongly inhibit GBM growth in
      vitro (P <0.01). Moreover, tumor-induced migration of MCs, although partially
      affected by the PTX cargo, remained statistically significant when compared with
      unprimed cells and this was confirmed in a 3D Matrigel model (P <0.01) and in a
      Trans-well assay (P <0.01). FN-MCs-PTX also disclosed considerable antiangiogenic
      properties. DISCUSSION: Our results suggest that the fibronectin-adherent
      population of MCs isolated from peripheral blood can be an effective tool to
      inhibit GBM growth. Given the relative facility to obtain such cells and the
      short time needed for their culture and drug loading this approach may have
      potential as an adjuvant therapy for GBM.

PMID- 28434807
TI  - Claimed effects, outcome variables and methods of measurement for health claims
      proposed under European Community Regulation 1924/2006 in the framework of
      protection against oxidative damage and cardiovascular health.
AB  - BACKGROUND AND AIMS: The high number of negative opinions from the European Food
      Safety Authority (EFSA) to the requests for authorization of health claims is
      largely due to the design of human intervention studies, including the
      inappropriate choice of outcome variables (OVs) and of their methods of
      measurement (MMs). The present manuscript reports the results of an investigation
      aimed to collect, collate and critically analyse the information in relation to
      claimed effects, OVs and MMs, in the context of protection against oxidative
      damage and cardiovascular health compliant with Regulation 1924/2006. METHODS AND
      RESULTS: Claimed effects, OVs and the related MMs were collected from EFSA
      Guidance documents and applications for authorization of health claims under
      Articles 13.5 and 14. The OVs and their MMs were evaluated only if the claimed
      effect was sufficiently defined and was considered beneficial by EFSA. The
      collection, collation and critical analysis of the relevant scientific literature
      consisted in the definition of the keywords, the PubMed search strategies and the
      creation of databases of references. The critical analysis of the OVs and their
      MMs was performed on the basis of the literature review and was aimed at defining
      the appropriateness of OVs and MMs in the context of the specific claimed
      effects. CONCLUSIONS: The information provided in this document could serve to
      EFSA for the development of further guidance on the scientific requirements for
      health claims, as well as to the stakeholders for the proper design of human
      intervention studies aimed to substantiate such health claims.

PMID- 28434808
TI  - [Psoas abscess secondary to perforated acute diverticulitis].

PMID- 28434809
TI  - Real-world performance of the new US HIV testing algorithm in medical settings.
AB  - BACKGROUND: Our medical center laboratory recently adapted its 24/7, two-hourly
      testing program to use an ARCHITECT-Multispot-viral load (AR-MS-VL) algorithm in
      place of a previous rapid test-immunofluorescence (RT-IF) algorithm. OBJECTIVES:
      We evaluated screening test performance, acute case detection, turnaround time
      and ability to resolve HIV status under the new algorithm. STUDY DESIGN: We
      considered consecutive HIV tests from January to November 2015. AR-MS-VL results
      at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG) were
      compared with RT-IF results at ZSFG and also with AR-MS-VL results in the
      recently completed CDC Screening Targeted Populations to Interrupt On-going
      Chains of HIV Transmission with Enhanced Partner Notification (STOP) Study for
      targeted testing of MSM at publicly funded testing sites in San Francisco.
      RESULTS: Among 21,985 HIV tests performed at ZSFG, 16,467 were tested by RT-IF
      and 5518 by AR-MS-VL. There were 321 HIV infections detected, of which 274 (84%)
      were known HIV+ cases, and 47 were newly identified HIV infections. Considering
      only patients of HIV-negative or -unknown status, prevalence was 0.22%. Under the
      AR-MS-VL algorithm, turnaround times for screening results and full algorithm
      results were 3 and 21h; status-unresolved cases were reduced (from 47% to 22%)
      compared with the RT-IF algorithm. The positive predictive value (PPV) of a new
      positive AR screening test was low (0.44) at ZSFG, where no acute infections were
      detected. At STOP Study sites where HIV prevalence was higher and acute infection
      was more common, the AR PPV was higher (0.93). All 24 false-positive AR screening
      tests at ZSFG had a signal/cutoff (S/CO) ratio of <15 and all 88 true-positive
      tests had S/CO ratio >15. Of 62 acute infections in the STOP Study, 23 (37%) had
      an S/CO<15. DISCUSSION: An AR-MS-VL algorithm is feasible and can return rapid
      results in a large medical center. In this setting, reactive 4th generation assay
      tests that are negative for HIV antibodies are typically false-positive with low
      S/CO ratios.

PMID- 28434810
TI  - Comparative performance of the GeeniusTM HIV-1/HIV-2 supplemental test in
      Florida's public health testing population.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) published
      updated guidelines in 2014 for the laboratory diagnosis of HIV in the United
      States, which recommend use of a supplemental immunoassay (IA) that
      differentiates HIV-1 from HIV-2 after a repeatedly reactive HIV-1/2
      antigen/antibody "Combo" screening test. In October 2014, Bio-Rad Laboratories
      introduced the FDA-cleared Geenius HIV-1/HIV-2 Supplemental assay and in July
      2016, it replaced the Multispot HIV-1/HIV-2 differentiation rapid test as the
      second test in the HIV diagnostic algorithm. OBJECTIVE: To compare performance of
      the new FDA-cleared Bio-Rad Geenius HIV-1/HIV-2 Supplemental assay and the Bio
      Rad Multispot HIV-1/HIV-2 differentiation assay for use as the primary
      supplemental test in the 2014 CDC/APHL HIV Diagnostic Algorithm. STUDY DESIGN:
      Two sets of specimens were used to assess the performance of Geenius; 340 select
      retrospective specimens, obtained through routine clinical submissions from
      individuals seeking HIV serostatus determinations and 10 known HIV-2 antibody
      reactive specimens provided by Bio-Rad Laboratories. Panels were created and
      characterized solely by in-house laboratory results. The panels consisted of:
      algorithm-defined "established HIV-1 infections" (n=250), "acute HIV-1
      infections" (n=20), "early HIV-1 infections" (n=10) and "false positive Combo
      specimens" (n=60). RESULTS: CONCLUSIONS: The Geenius assay provides significant
      advantages over Multispot as an appropriate replacement for the primary
      supplemental test in the HIV Diagnostic Algorithm. In this retrospective study,
      Geenius was highly concordant with Multispot, reclassified some acute and early
      algorithm-defined HIV-1 positive specimens and demonstrated a potential decrease
      in the number HIV-1 RNA nucleic acid amplification tests needed to complete the
      diagnostic algorithm.

PMID- 28434811
TI  - Predicting and planning for SIEA flap utilisation in breast reconstruction: An
      algorithm combining pre-operative computed tomography analysis and intra
      operative angiosome assessment.
AB  - BACKGROUND: Low flap complication rates and excellent aesthetic outcomes are now
      commonplace in breast reconstruction. As a result, attention is now being
      focussed on minimising donor site morbidity. Despite its potential donor site
      advantages, the superficial inferior epigastric artery (SIEA) flap is often
      discounted, given concerns about the high flap failure rates. In this study, we
      present our experience of using the SIEA flap in breast reconstruction and
      provide an algorithm based on pre-operative computed tomography angiography (CTA)
      to aid pre-operative planning. METHODS: A retrospective analysis of SIEA flap
      breast reconstruction cases performed at our unit between 2009 and 2016 was
      performed and outcomes were assessed. In addition, the patients' pre-operative
      CTA images were assessed and compared to those of a matched group of patients who
      underwent deep inferior epigastric artery perforator (DIEP) flap breast
      reconstruction. RESULTS: Twenty-six patients who underwent SIEA flap breast
      reconstruction were eligible for inclusion. No flaps were lost. Donor site seroma
      rate was 20%. The largest SIEA diameter in those who underwent an SIEA flap was
      significantly larger (p = 0.0001) than in those who underwent DIEP flap breast
      reconstruction. Significantly more number of patients who underwent SIEA flap
      breast reconstruction had a SIEA diameter greater than or equal to that of the
      largest DIEP flap perforator (p = 0.0001) in the group where a DIEP flap was used
      for breast reconstruction. CONCLUSION: High success rates can be achieved with
      abdominal flaps based on the superficial vascular system and careful pre- and
      perioperative assessment of patients.

PMID- 28434812
TI  - ITK inhibition for the targeted treatment of CTCL.

PMID- 28434813
TI  - Rhythmic expressed clock regulates the transcription of proliferating cellular
      nuclear antigen in teleost retina.
AB  - Teleost fish continues to grow their eyes throughout life with the body size. In
      Astatotilapia burtoni, the fish retina increases by adding new retinal cells at
      the ciliary marginal zone (CMZ) and in the outer nuclear layer (ONL). Cell
      proliferation at both sites exhibits a daily rhythm in number of dividing cells.
      To understand how this diurnal rhythm of new cell production is controlled in
      retinal progenitor cells, we studied the transcription pattern of clock genes in
      retina, including clock1a, clock1b, bmal1a (brain and muscle ARNT-Like), and
      per1b (period1b). We found that these genes have a strong diurnal rhythmic
      transcription during light-dark cycles but not in constant darkness. An
      oscillation in pcna transcription was also observed during light-dark cycles, but
      again not in constant darkness. Our results also indicate an association between
      Clock proteins and the upstream region of pcna (proliferating cellular nuclear
      antigen) gene. A luciferase reporter assay conducted in an inducible clock
      knockdown cell line further demonstrated that the mutation on predicted E-Boxes
      in pcna promoter region significantly attenuated the transcriptional activation
      induced by Clock protein. These results suggested that the diurnal rhythmic
      expression of clock genes in A. burtoni retina could be light dependent and might
      contribute to the daily regulation of the proliferation of the retina progenitors
      through key components of cell cycle machinery, for instance, pcna.

PMID- 28434814
TI  - Novel protein biomarkers associated with coronary artery disease in statin
      treated patients with familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is the most common and serious
      monogenic disorder of lipid metabolism. The incidence of coronary artery disease
      (CAD) varies among both treated and untreated FH patients. OBJECTIVE: The aim of
      the study was to utilize proteomics to identify novel protein biomarkers that
      differentiate genetically confirmed heterozygous patients with FH at high CAD
      risk from those at low CAD risk. METHODS: Sixty genetically confirmed FH patients
      were recruited and stratified into (1) asymptomatic FH with low atherosclerotic
      burden (FH, n = 20); (2) asymptomatic FH with high atherosclerotic burden (FH +
      Ca, n = 20); and (3) FH with previously confirmed symptomatic CAD (FH + CAD, n =
      20). RESULTS: Six new potential proteins were identified; leucine-rich alpha-2
      glycoprotein (LRG1), inter-alpha-trypsin inhibitor heavy chain H3, complement C4
      B (C4B), complement C1q subcomponent subunit B (C1QB), monocyte differentiation
      antigen (CD14), and histidine-rich glycoprotein (HRG). There were significant
      associations between gender and C4B (Z = 2.31, P = .021), C1QB (Z = 2.49, P =
      .013), CD14 (Z = 2.17, P = .03), and HRG (Z = 2.14, P = .033). There were
      significant associations between smoking and LRG1 (chi22 = 6.59, P = .037), CB4
      (chi22 = 7.85, P = .02), and HRG (chi22 = 6.11, P = .047). All the peptides were
      significantly associated with advanced CAD stages, independently of age and
      smoking. However, the absence of the proteins was the strongest marker. The most
      accurate association with CAD was HRG (area under the receiver operating
      characteristic curve = 0.922), whereas LRG1, C4B, and C1QB were also associated
      with CAD (area under the receiver operating characteristic curve >0.9). For
      either coronary atherosclerosis or CAD, LRG1, C4B, C1QB, and HRG were relatively
      well associated. CONCLUSIONS: The present study has identified 6 novel protein
      biomarkers that are associated with more advanced stages of atherosclerotic
      disease and subsequent coronary events in patients with heterozygous FH.

PMID- 28434815
TI  - Is Canada Ready to Adopt Maternal Placental Growth Factor Testing to Improve
      Clinical Outcomes for Women with Suspected Preeclampsia?

PMID- 28434816
TI  - Co-existing Arterial Pathology: Stenosis and Aneurysm in Carotid Territory: To
      worry?

PMID- 28434817
TI  - The protective effect of hyperoside on carbon tetrachloride-induced chronic liver
      fibrosis in mice via upregulation of Nrf2.
AB  - CONTEXT: Hyperoside was used to treat cardiovascular disease for many years in
      China. It was shown great effect on regulation of lipid metabolism. But there is
      lack of reports about the effects of hyperoside on liver diseases. OBJECTIVE:
      This study was designed to investigate the potentially protective effects of
      hyperoside and the role of transcription factor nuclear factor-erythroid 2(NF-E2)
      related factor 2 (Nrf2) signaling in the regulation on Carbon Tetrachloride
      (CCl4)-induced chronic liver fibrosis in mice. MATERIALS AND METHODS: All mice
      were divided into six groups containing 6 animals per group. Mice in different
      group were given relative processing for 4 weeks. The potentially protective
      effects of hyperoside on CCl4-induced chronic liver fibrosis in mice were
      depicted histologically and biochemically. RESULTS: CCl4 administration caused a
      marked increase in the levels of serum aminotransferases, serum monoamine oxidase
      (MAO) and lipid peroxidation, MAO in mouse liver homogenates. Also decreased
      activities of cellular antioxidant defense enzymes were found after CCl4
      exposure. Histopathological changes induced by CCl4 including regenerative
      nodules, deteriorated parenchyma. Hyperoside and silymarin reduced these changes
      and attenuated the pathological effects of CCl4 induced liver injury. In
      addition, hyperoside exhibited antioxidant effects in vitro. In Western blot
      analysis, the protein level of Nrf2 was downregulated after CCl4 administration
      and reversed by hyperoside. CONCLUSION: Hyperoside increased the activity of the
      antioxidant and phase II detoxifying enzymes through the activation of Nrf2
      nuclear translocated in the CCl4-induced liver fibrosis mice.

PMID- 28434818
TI  - Expression of A-kinase anchor protein 13 and Rho-associated coiled-coil
      containing protein kinase in restituted and regenerated mucosal epithelial cells
      following mucosal injury and colorectal cancer cells in mouse models.
AB  - We demonstrate the expression patterns of A-kinase anchor protein 13 (AKAP13), a
      scaffold protein that acts upstream of Rho signaling, and Rho-associated coiled
      coil containing protein kinase (ROCK) 1/2 in mouse colorectal cancer and during
      the healing stage of mouse colitis. BALB/c mice received an intraperitoneal
      injection of azoxymethane at 10mg/kg, followed by two 7-day cycles of 3% dextran
      sulfate sodium (DSS) administered through their drinking water to induce colon
      cancer, or a 7-day administration of 4% DSS to induce colitis. The colorectal
      tissue was then analyzed for gene expression, histopathology, and
      immunohistochemistry. In the colorectal cancer, AKAP13 and ROCK1/2 were highly
      expressed in adenocarcinoma compared to the control tissue and low-grade
      dysplasia. In colitis, AKAP13 and ROCK1 were highly expressed in the restituted
      and regenerated mucosa but were only moderately expressed in the injured mucosal
      epithelium, compared to the normal epithelium that exhibited weak expression
      levels. ROCK2 was weakly expressed in these cells, consistent with the expression
      of AKAP13 and ROCK1. Furthermore, we found several clumps of epithelial cells
      expressing AKAP13 and ROCK1/2 in the lamina propria during the mucosal healing
      process, and these cells also expressed interleukin-6, which is a multipotential
      cytokine for both inflammation and healing. These data suggest that AKAP13 was
      expressed in relation with ROCK1/2, which probably play an overall role in both
      mucosal healing and tumorigenesis.

PMID- 28434819
TI  - Functional Test of the Hemiparetic Upper Extremity: A Rasch Analysis With
      Theoretical Implications.
AB  - OBJECTIVE: To investigate the measurement properties of the Functional Test of
      the Hemiparetic Upper Extremity (FTHUE) and examine how its score may or may not
      inform design of a rehabilitation program. DESIGN: The FTHUE was recently used in
      the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation randomized
      controlled trial. This circumstance provided the opportunity to examine the
      psychometric properties of the FTHUE as it pertains to contemporary poststroke
      rehabilitation and recovery models. SETTING: Outpatient rehabilitation clinic.
      PARTICIPANTS: Participants (N=109; mean age, 61.2+/-13.5y; mean days poststroke,
      46+/-20.3) with resultant hemiparesis in the upper extremity. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Dimensionality was examined with confirmatory
      factor analysis (CFA), and person and item measures were derived with Rasch item
      response analysis. Therapists' notes were also reviewed. RESULTS: The CFA results
      support unidimensionality, and 16 of 17 items fit the Rasch model. The Rasch
      person separation (2.17) and item separation (4.50) indices, ability strata
      (3.22), person reliability (.82), and item reliability (.95) indicate good
      measurement properties. Item difficulties ranked from -6.46 to 3.43 logits;
      however, there was a substantial ceiling effect of person measures. Post hoc
      examination of therapists' written observations indicated that the scoring
      criteria are not sensitive to the movement strategy used for task completion.
      CONCLUSIONS: The FTHUE's item difficulty hierarchy indicated that scores
      adequately distinguished the ability to perform simple versus complex motor
      movements of functional tasks. However, the FTHUE scoring method did not allow
      inclusion of the type of movement strategy used to accomplish task items.
      Therefore, we suggest modifications to the FTHUE that would allow it to be used
      for collaborative treatment planning and align well with more contemporary
      perspectives on treatment theory.

PMID- 28434820
TI  - Interrelationships of metal transfer factor under wastewater reuse and soil
      pollution.
AB  - The transfer of heavy metals under soil pollution wastewater reuse was studied in
      a Greenhouse experiment using a randomized block design, including 6 treatments
      of heavy metals mixtures composed of Zn, Mn, Cd, Co, Cu, Cr, Ni, and Pb, where
      each metal was taking part in the mixture with 0, 10, 20, 30, 40, 50 mg/kg
      respectively, in four replications. The Beta vulgaris L (beet) was used as a test
      plant. It was found that the metal transfer factors were statistically
      significantly related to the: (i) DTPA extractable soil metals, (ii) the soil
      pollution level as assessed by the pollution indices, (iii) the soil pH, (iv) the
      beet dry matter yield and (v) the interactions between the heavy metals in the
      soil. It was concluded that the Transfer Factor is subjected to multifactor
      effects and its real nature is complex, and there is a strong need for further
      study for the understanding of its role in metal-plant relationships.

PMID- 28434821
TI  - An overview of geophysical technologies appropriate for characterization and
      monitoring at fractured-rock sites.
AB  - Geophysical methods are used increasingly for characterization and monitoring at
      remediation sites in fractured-rock aquifers. The complex heterogeneity of
      fractured rock poses enormous challenges to groundwater remediation
      professionals, and new methods are needed to cost-effectively infer fracture and
      fracture-zone locations, orientations and properties, and to develop conceptual
      site models for flow and transport. Despite the potential of geophysical methods
      to "see" between boreholes, two issues have impeded the adoption of geophysical
      methods by remediation professionals. First, geophysical results are commonly
      only indirectly related to the properties of interest (e.g., permeability) to
      remediation professionals, and qualitative or quantitative interpretation is
      required to convert geophysical results to hydrogeologic information. Additional
      demonstration/evaluation projects are needed in the site remediation literature
      to fully transfer geophysical methods from research to practice. Second,
      geophysical methods are commonly viewed as inherently risky by remediation
      professionals. Although it is widely understood that a given method may or may
      not work at a particular site, the reasons are not always clear to end users of
      geophysical products. Synthetic modeling tools are used in research to assess the
      potential of a particular method to successfully image a target, but these tools
      are not widely used in industry. Here, we seek to advance the application of
      geophysical methods to solve problems facing remediation professionals with
      respect to fractured-rock aquifers. To this end, we (1) provide an overview of
      geophysical methods applied to characterization and monitoring of fractured-rock
      aquifers; (2) review case studies showcasing different geophysical methods; and
      (3) discuss best practices for method selection and rejection based on synthetic
      modeling and decision support tools.

PMID- 28434823
TI  - Influence of serum and polystyrene plate type on stability of Candida albicans
      biofilms.
AB  - Adhesion is a crucial initial step in microbial biofilm formation. Firm
      attachment to a target surface subsequently ensures successful colonization and
      survival despite turbulent conditions. In the laboratory, polystyrene plates are
      commonly used in biofilm experiments and the 'washing/rinse steps' before
      staining are critical for assaying biofilm viability. However, these rinse steps
      risk the removal (partially or entirely) of the formed biofilm, resulting in
      inconsistent results. The aim of the present study was to optimize conditions for
      firmer biofilms, less prone to disruption and thus significantly reducing well-to
      well variability. Candida albicans SC5314 was used in five different polystyrene
      96-well plates from four different manufacturers. Irrespective of how gently we
      performed the rinse, biofilms came off certain polystyrene plates more easily
      compared to others. Importantly, preconditioning the polystyrene surfaces with
      foetal bovine serum (FBS) had a negative impact on firm biofilm attachment.
      Costar(r) plates provided the most suitable surface for firm biofilm attachment,
      both in the presence and absence of FBS. Substratum properties even among
      seemingly identical synthetic materials may influence biofilm attachment and its
      subsequent sturdiness, affecting experimental results.

PMID- 28434824
TI  - Multiple pathogen biomarker detection using an encoded bead array in droplet PCR.
AB  - We present a droplet PCR workflow for detection of multiple pathogen DNA
      biomarkers using fluorescent color-coded Luminex(r) beads. This strategy enables
      encoding of multiple singleplex droplet PCRs using a commercially available bead
      set of several hundred distinguishable fluorescence codes. This workflow provides
      scalability beyond the limited number offered by fluorescent detection probes
      such as TaqMan probes, commonly used in current multiplex droplet PCRs. The
      workflow was validated for three different Luminex bead sets coupled to target
      specific capture oligos to detect hybridization of three microorganisms infecting
      poultry: avian influenza, infectious laryngotracheitis virus and Campylobacter
      jejuni. In this assay, the target DNA was amplified with fluorescently labeled
      primers by PCR in parallel in monodisperse picoliter droplets, to avoid
      amplification bias. The color codes of the Luminex detection beads allowed
      concurrent and accurate classification of the different bead sets used in this
      assay. The hybridization assay detected target DNA of all three microorganisms
      with high specificity, from samples with average target concentration of a single
      DNA template molecule per droplet. This workflow demonstrates the possibility of
      increasing the droplet PCR assay detection panel to detect large numbers of
      targets in parallel, utilizing the scalability offered by the color-coded Luminex
      detection beads.

PMID- 28434822
TI  - Current and potential imaging applications of ferumoxytol for magnetic resonance
      imaging.
AB  - Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool.
      Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme,
      AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is
      feasible in patients with impaired renal function. Other attractive imaging
      features of i.v. ferumoxytol include a prolonged blood pool phase and delayed
      intracellular uptake. With its unique pharmacologic, metabolic, and imaging
      properties, ferumoxytol may play a crucial role in future magnetic resonance
      imaging of the central nervous system, various organs outside the central nervous
      system, and the cardiovascular system. Preclinical and clinical studies have
      demonstrated the overall safety and effectiveness of this novel contrast agent,
      with rarely occurring anaphylactoid reactions. The purpose of this review is to
      describe the general and organ-specific properties of ferumoxytol, as well as the
      advantages and potential pitfalls associated with its use in magnetic resonance
      imaging. To more fully demonstrate the applications of ferumoxytol throughout the
      body, an imaging atlas was created and is available online as supplementary
      material.

PMID- 28434826
TI  - The accuracy of patient specific implant prebented with 3D-printed rapid
      prototype model for orbital wall reconstruction.
AB  - BACKGROUND: This study evaluated the accuracy of blow out fracture reduction
      using 3D-printed rapid prototyping (RP) skull modeling. PATIENTS AND METHODS:
      Retrospective review was performed for 82 patients who underwent post-traumatic
      orbital wall fracture reduction between 2012 and 2014. Patients were divided into
      two groups according to the use of 3D-printed RP skull model reproduced by
      mirroring technique, onto which a titanium mesh was anatomically molded. Using
      computed tomographic scans, the areas of pre- and post-operative orbital wall
      defect, the layout angles of the titanium mesh, and the gap lengths between the
      implant and fracture margin were compared between the two groups. RESULTS: Of the
      82 patients identified, 46 and 36 were diagnosed with medial and inferior orbital
      wall fractures, respectively. Bone defect area of the RP group was significantly
      reduced in comparison with that of the conventional group (8.03 +/- 3.5% versus
      18.7 +/- 15.41% for medial wall fractures, 7.14 +/- 5.74% versus 12.8 +/- 4.92%
      for inferior wall fractures, respectively, p < 0.01). Satisfactory results were
      achieved regarding the layout angles and the gap lengths, presenting
      significantly reduced values in the RP group compared to that in the conventional
      group (p < 0.01). CONCLUSIONS: More accurate restoration of traumatic orbital
      wall fractures can be achieved using patient-specific 3D-printed RP skull models.

PMID- 28434827
TI  - Comprehensive and reliable classification system for primary diagnosis of cleft
      lip and palate.
AB  - OBJECTIVE: Due to the lack of a universally accepted classification system, we
      are aiming to introduce a modified comprehensive, precise and relatively simple
      classification system for primary diagnosis of cleft lip and palate. METHODS: The
      proposed classification is based on the Kernahan's striped Y diagram with more
      details in cleft extent and with the addition of severity scores to each cleft
      component. Clear definitions of cleft extents and severity degrees were described
      based on 400 consecutive primary cases. Two medical students were taught the
      classification then diagnosed photographs of 100 cases twice to test its
      reliability. RESULTS: The students' results were 11% and 13% wrong diagnoses for
      student 1 and 2 in the first time, 8% and 10% in the second time, respectively.
      The inter-rater reliability for the two students in the first and second time was
      0.716 and 0.878, respectively. The intra-rater reliability for student 1 and 2
      were 0.826 and 0.755 respectively. The average duration to diagnose a case was
      less than a minute. CONCLUSION: This classification is comprehensive and records
      many diagnostic variables with high reliability and precision.

PMID- 28434825
TI  - RNA-binding proteins in human oogenesis: Balancing differentiation and self
      renewal in the female fetal germline.
AB  - Primordial germ cells undergo three significant processes on their path to
      becoming primary oocytes: the initiation of meiosis, the formation and breakdown
      of germ cell nests, and the assembly of single oocytes into primordial follicles.
      However at the onset of meiosis, the germ cell becomes transcriptionally
      silenced. Consequently translational control of pre-stored mRNAs plays a central
      role in coordinating gene expression throughout the remainder of oogenesis; RNA
      binding proteins are key to this regulation. In this review we examine the role
      of exemplars of such proteins, namely LIN28, DAZL, BOLL and FMRP, and highlight
      how their roles during germ cell development are critical to oogenesis and the
      establishment of the primordial follicle pool.

PMID- 28434828
TI  - Correlation between single photon emission computed tomography and
      histopathologic findings in condylar hyperplasia of the temporomandibular joint.
AB  - PURPOSE: To analyse the correlation between the level of activity measured in the
      single photon emission computed tomography (SPECT) and the pathological findings
      in patients with condylar hyperplasia (CH). MATERIALS AND METHODS: All patients
      evaluated in our department between 2007 and 2014 with a diagnosis of condylar
      hyperplasia who had undergone SPECT, evidenced signs of activity, and had
      undergone surgery were included. We included 28 patients, of whom 20 were women
      and 8 men. RESULTS: The male:female ratio was 2,5:1. The mean age of the subjects
      was 24.4 years at the time of diagnosis (with a range between 14 and 42 years).
      In 19 cases the affected condyle was the right, and in the remaining 9 it was the
      left (ratio R:L 2,1:1). On the SPECT, in 16 patients a high level of activity was
      identified (57.1%) and in the remaining 12 a low level (42.9%). Only 13 patients
      (6 in the low-activity group and 7 in the high-activity group) presented with
      islands of cartilage. When comparing the results between the two groups, the main
      differences were observed in the parameters related to the islands of cartilage.
      These were more frequent in the group with high activity compared with low
      activity (5.5 versus 0 per mm2 of median). Besides being more frequent, these
      islands were larger (more than double) in the high-activity group (385.1 MUm
      versus 169.7 MUm of median). This is the only statistically significant
      difference found, a fact that can be explained by the small sample size in the
      study. CONCLUSION: Radioisotope tests are the best indicator of the level of
      activity in condylar hyperplasia, which seems to be directly related to the
      intensity signal collection.

PMID- 28434829
TI  - Use of cutting guides during craniosynostosis sequelae surgery: A comparative
      study between computer-assisted planning and post-operative results.
AB  - BACKGROUND: The authors compared results of craniofacial reconstruction surgery
      using cutting guides with planned reconstruction on patients presenting
      craniosynostosis surgery sequelae. METHODS: This is a retrospective study
      performed on seven patients who had undergone craniofacial reconstructive surgery
      in University Hospital Center of Tours (France) in 2015. Patients had long-term
      sequelae of trigonocephaly and anterior plagiocephaly surgery. 3D computer model
      was constructed, based on CT scans and used for surgical planning. Cutting guides
      were realized to use patient autologous bone. Post-operative 3D cranioplasty was
      superimposed to the 3D pre-operative to determine the minimal distance between
      each point of the post-operative flap and its pre-operative point corresponding.
      RESULTS: Mean of minimal distances calculated per patient ranged from 0.89 mm to
      1.85 mm. The best result for percentage of points having the minimal distance
      inferior to 1.8 mm was 98.2 percent; the worst result was 55 percent. This value
      ranged from 77.5 to 98.2 percent for trigonocephaly cases. This value ranged from
      55 to 77.5 percent for plagiocephaly cases. No significant difference was found
      between pre and post-operative areas and volumes of each flap, p = 0.12 and p =
      0.19 respectively. CONCLUSION: Using cutting guides facilitates complex
      craniofacia reconstructions with patient autologous bone and obtains precise and
      reproducible results.

PMID- 28434830
TI  - Bone formation of demineralized human dentin block graft with different
      demineralization time: In vitro and in vivo study.
AB  - OBJECTIVE: To evaluate structural and physicochemical characteristics of
      demineralized human dentin block with increasing demineralization time and to
      assess new bone formation when onlay grafted at different demineralization times
      in rat calvaria. STUDY DESIGN: Extracted human permanent teeth were pretreated
      and demineralized for 10-90 min. Scanning electron microscopy, X-ray diffraction
      analysis, inductively coupled plasma spectrometry, and energy dispersive X-ray
      analysis were performed. Demineralized dentin blocks (DDBs) with the
      representatives of the different demineralization times (10 and 60 min) were
      implanted in vivo onto rat calvaria (male Sprague-Dawley, n = 20 for each
      carrier). For controls, collagen sponge and human freeze-dried corticocancellous
      bone blocks (FDBB) were implanted onto calvaria (n = 20). The rats were
      sacrificed 2 or 8 weeks postoperatively and evaluated radiographically,
      histologically, and histomorphometrically. RESULTS: With increasing
      demineralization time, the surface structure of dentin blocks showed increased
      number and size of dentinal tubules. Moreover, the organic components increased,
      whereas inorganic components decreased. Crystallinity decreased sharply between
      10 and 30 min demineralization time. In our in vivo study, at both time points,
      animals with DDBs showed significantly better bone formation than controls (p <
      0.05). The DDB/60 group showed significantly increased new bone area and bone
      density than the DDB/10 group at 8 weeks (p < 0.05), but showed higher resorption
      that significantly decreased total augmented area compared with the DDB/10 group
      (p < 0.05). CONCLUSION: DDB increased new bone formation and bone density.
      Further studies are needed to determine the optimal demineralization time to
      maximize space maintenance and bone formation of the graft material.

PMID- 28434831
TI  - Submuscular Versus Subcutaneous Ulnar Nerve Transposition: A Cadaveric Model
      Evaluating Their Role in Primary Ulnar Nerve Repair at the Elbow.
AB  - PURPOSE: To investigate the length gained from subcutaneous and submuscular
      transposition of the ulnar nerve at the elbow. Specifically, the study aimed to
      define an expected nerve gap able to be overcome, and to determine if a
      difference between transposition techniques exists. METHODS: Eleven cadaveric
      specimens from the scapula to fingertip were procured. In situ decompression and
      mobilization of the ulnar nerve at the elbow followed by simulated laceration of
      the nerve was performed. Nerves were marked 5 mm from the laceration site to
      facilitate overlap measurement and to simulate nerve end preparation to viable
      fascicles before primary coaptation. Nerve ends were attached to spring gauges
      set at 100 g of tension (strain <= 10%). Measurements of nerve overlap were
      obtained in varying degrees of wrist (0 degrees , 30 degrees , 60 degrees ) and
      elbow (0 degrees , 15 degrees , 30 degrees , 45 degrees , 60 degrees , 90 degrees
      ) flexion. Measurements were performed after in situ decompression and
      mobilization, and then repeated after both subcutaneous and submuscular
      transposition. RESULTS: Ulnar nerve transposition was found to increase nerve
      overlap at an elbow flexion of 30 degrees  or greater. No difference was seen
      between subcutaneous and submuscular transpositions at all wrist and elbow
      positions. In situ decompression and mobilization alone provided an average of
      3.5 cm of length gain with the elbow extended. Transposition in conjunction with
      clinically feasible wrist and elbow flexion (30 degrees  and 60 degrees ,
      respectively) provided 5.2 cm of length gain. Controlling for mobilization, a
      statistically significant increase in overlap of approximately 2 cm was gained
      from transposition. CONCLUSIONS: Although mobilization combined with wrist and
      elbow flexion may afford substantial gap reduction and should be used initially
      when approaching proximal ulnar nerve lacerations, transposition should be
      considered when faced with a large nerve gap greater than 3 cm at the elbow. No
      difference was seen between submuscular and subcutaneous transposition
      techniques. CLINICAL RELEVANCE: This study defines the extent an ulnar nerve gap
      at the elbow can be overcome by in situ mobilization, joint positioning, and
      transposition. It additionally compares the efficacy of submuscular and
      subcutaneous transposition techniques in closing this gap.

PMID- 28434832
TI  - Conventional Versus Computer-Assisted Corrective Osteotomy of the Forearm: a
      Retrospective Analysis of 56 Consecutive Cases.
AB  - PURPOSE: Accuracy and feasibility of corrective osteotomies using 3-dimensional
      planning tools and patient-specific instrumentation has been reported by multiple
      authors with promising results. However, studies describing clinical outcomes
      following these procedures are rare. Therefore, the purpose of this study was to
      compare the results of computer-assisted corrective osteotomies of the diaphyseal
      and distal radius with a conventional non-computer-assisted technique regarding
      duration of surgery, consolidation of the osteotomy, and complications. Also,
      subjective and objective clinical outcome parameters were assessed. METHODS: We
      retrospectively compared the results of 31 patients who underwent a corrective
      osteotomy performed conventionally with 25 patients treated with a computer
      assisted method (CA) using patient-specific instrumentation. Baseline data were
      similar among both groups. The duration of surgery, bony consolidation,
      complications, gain in range of motion, and subjective outcome were recorded.
      RESULTS: The mean operating time was significantly shorter in the CA group
      compared with the conventional group. After 12 weeks, significantly more
      osteotomies were considered healed in the CA group compared with the conventional
      group. Two patients in the CA group required revision surgery to treat nonunion
      of the osteotomy. Otherwise clinical results were similar among both groups.
      CONCLUSIONS: The results demonstrate that the computer-assisted method
      facilitates shorter operation times while providing similar clinical results.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 28434833
TI  - Metaphyseal Versus Diaphyseal Ulnar Shortening Osteotomy for Treatment of Ulnar
      Impaction Syndrome: A Comparative Study.
AB  - PURPOSE: To compare the clinical and radiographic outcomes and complication rates
      of diaphyseal and metaphyseal ulnar shortening osteotomies for the treatment of
      ulnar abutment syndrome. METHODS: We performed a retrospective study comparing 35
      patients who underwent either a metaphyseal (n = 14) or diaphyseal (n = 21)
      osteotomy. Radiographic and clinical outcomes were compared. Complication rates
      including infection, hardware removal, and reoperations were also assessed.
      RESULTS: There were no differences in patient characteristics, ulnar variance, or
      pain and functional scores between groups. Metaphyseal osteotomy surgery time was
      shorter (45.5 vs 71.7 minutes) and resulted in greater ulnar shortening (4.8 vs
      3.4 mm) compared with diaphyseal osteotomies. At an average 19.2-month follow-up,
      metaphyseal osteotomies were associated with greater improvement in pain and
      Quick-Disabilities of the Arm, Shoulder, and Hand questionnaire scores. The need
      for implant removal was the same in both groups. There were no complications in
      either group. CONCLUSIONS: Results from this study suggest that metaphyseal
      osteotomies are a safe and effective alternative to diaphyseal osteotomies for
      the management of ulnar abutment syndrome. Although improved surgical time and
      postoperative outcomes are encouraging, further large-scale and properly powered
      studies with long-term outcomes will help characterize the benefit of one
      technique over another. Ultimately, the decision between a metaphyseal and
      diaphyseal osteotomy may be surgeon preference. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 28434834
TI  - The Zitelli Bilobed Flap on Skin Coverage After Mucous Cyst Excision: A
      Retrospective Cohort of 33 Cases.
AB  - PURPOSE: To study the time to wound healing and recurrence rate achieved in the
      treatment of distal interphalangeal joint mucous cysts using the Zitelli modified
      bilobed flap. METHODS: We surgically treated 33 patients from January 2006 to
      June 2015. We assessed demographic data, comorbidities, location and size of the
      cyst, time to wound healing, and complications. RESULTS: The most affected finger
      was the right middle finger. All flaps survived and wounds healed in 14 days on
      average. The mucous cyst recurred in 1 of 33 cases. There were no major
      complications. CONCLUSIONS: The Zitelli bilobed flap can provide good-quality
      skin coverage over the distal interphalangeal joint in a short period. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 28434835
TI  - Use of a Bicortical Button to Safely Repair the Distal Biceps in a Two-Incision
      Approach: A Cadaveric Analysis.
AB  - PURPOSE: No consensus has been reached on the most effective anatomic approach or
      fixation method for distal biceps repair. It is our hypothesis that, using a
      cortical biceps button through a 2-incision technique, the distal biceps can be
      safely and anatomically repaired. METHODS: A 2-incision biceps button distal
      biceps repair was completed on 10 fresh-frozen cadavers. The proximity of the
      guide pin to the critical structures of the forearm, including the posterior
      interosseous nerve and recurrent radial artery, was measured. The location of
      repair was mapped and compared with anatomic insertion. RESULTS: The average
      distance from the tip of the guide pin to the posterior interosseous nerve was
      11.4 mm (range, 8-14 mm). The average distance from the tip of the guide pin to
      the recurrent radial artery was 12.5 mm (range, 8-19 mm). The distal biceps
      tendon was repaired to the anatomic insertion site on the tuberosity using the
      biceps button technique in all specimens. CONCLUSIONS: The 2-incision biceps
      button repair described here allows safe and accurate repair of the tendon to the
      radial tuberosity in this cadaveric study. CLINICAL RELEVANCE: The goal of distal
      biceps repair is to safely, securely, and anatomically repair the torn biceps
      tendon to the radial tuberosity. The most commonly performed techniques (single
      anterior incision with cortical button and the double-incision procedure with
      bone tunnels and trough) have limitations. A 2-incision button repair safely and
      anatomically repairs the distal biceps tendon.

PMID- 28434836
TI  - Retrograde superselective intra-arterial chemotherapy and daily concurrent
      radiotherapy for T2-4N0 tongue cancer: control of occult neck metastasis.
AB  - OBJECTIVE: To evaluate the therapeutic results and control of occult neck
      metastasis in patients with T2-4N0 oral tongue squamous cell carcinoma treated
      with retrograde superselective intra-arterial chemotherapy and daily concurrent
      radiotherapy. STUDY DESIGN: Forty-two patients with T2-4N0 tongue cancer (17 with
      late T2; 13 with T3; and 12 with T4a disease, M0) were treated with intra
      arterial chemoradiotherapy. Treatment consisted of retrograde superselective
      intra-arterial chemotherapy (docetaxel 50-70 mg/m2, cisplatin 125-175 mg/m2) and
      daily concurrent radiotherapy (50-70 Gy) for 5-7 weeks. RESULTS: The median
      follow-up for all patients was 46.5 months (range, 8-105 months). Primary-site
      complete response was achieved in 42 of 42 cases (100%). Three-year overall
      survival, progression-free survival, and local control rates were 85.0%, 77.8%,
      and 91.7%, respectively. Delayed neck metastasis was detected in 5 of 42 cases
      (11.9%). Grade 3 or 4 toxic changes included oral mucositis in 92.9%, neutropenia
      in 21.4%, and thrombocytopenia in 4.8%. Grade 3 toxicities included anemia in
      16.7%, radiation dermatitis in 9.5%, nausea in 4.8%, and fever in 2.4%.
      CONCLUSIONS: Retrograde superselective intra-arterial chemotherapy for T2-4N0
      tongue cancer provided good overall survival and local control rates and was
      effective for occult neck metastasis.

PMID- 28434838
TI  - Comment re: "Optimize CA19-9 in detecting pancreatic cancer by Lewis and Secretor
      genotyping".

PMID- 28434837
TI  - Metabolic syndrome components and diabetes incidence according to the presence or
      absence of impaired fasting glucose: The Japan Epidemiology Collaboration on
      Occupational Health Study.
AB  - BACKGROUND: We prospectively examined the association of diabetes risk with the
      number of metabolic abnormalities, as well as their combinations, according to
      the presence or absence of impaired fasting glucose (IFG) in a large-scale
      Japanese working population. METHODS: Participants included 55,271 workers at 11
      companies who received periodic health check-ups between 2008 and 2013. The
      metabolic syndrome (MetS) components were defined using the 2009 Joint Interim
      Statement. IFG was defined as fasting plasma glucose 5.6-6.9 mmol/L. Diabetes
      newly diagnosed after the baseline examination was defined according to the
      American Diabetes Association criteria. We calculated the hazard ratios (HRs) for
      diabetes incidence using the Cox proportional hazards model. RESULTS: During the
      follow-up period (median 4.95 years), 3183 subjects developed diabetes. In
      individuals with normal fasting glucose levels, the risk of diabetes increased
      steadily with the increasing number of MetS components; the multivariable
      adjusted HRs for incident diabetes for the number of MetS components were 2.0,
      4.3, 7.0, and 10.0 for one, two, three, or four MetS components, respectively,
      compared with the absence of components. A similar association was observed among
      individuals with IFG; the corresponding HRs were 17.6, 23.8, 33.9, and 40.7. The
      combinations that included central obesity appeared to be more strongly
      associated with diabetes risk than other combinations with the same number of
      MetS components within the same glucose status. CONCLUSIONS: Our findings
      indicate that risk stratification of individuals by the presence or absence of
      IFG and the number of MetS components can detect individuals with a high risk of
      diabetes.

PMID- 28434839
TI  - The evolution in the management of aortic valve disease: From surgical techniques
      to transcatheter interventions.

PMID- 28434840
TI  - Exercise versus targeting of endocannabinoid system for atheromatic plaque
      stabilization. Opposing or complementary roles?

PMID- 28434842
TI  - A simple and non-invasive method for analyzing local immune responses in vivo
      using fish fin.
AB  - Immunocompetence is an important parameter that reflects disease resistance in
      fish. Very few methods to examine immunocompetence in vivo have been developed,
      even for mammals. In the present study, we present a unique method for analyzing
      local immune responses using fish fin. We first demonstrated the migration of
      granulocytes to the site of zymosan injection in fin in a dose-dependent manner
      and that this could be easily observed macroscopically due to the fin membrane
      transparency. We also demonstrated phagocytic activity of accumulated leukocytes
      after zymosan administration and that almost all phagocytes were granulocytes. In
      addition, we succeeded to detect respiratory burst activity of granulocytes in
      vivo without any in vitro treatment of cells, indicating that our present method
      is suitable for the analysis of granulocyte phagocytic function in vivo. The
      method provides a unique tool applicable for fishes that possess transparent fins
      and may lead to better understanding of the mechanisms of local immune responses
      in fish.

PMID- 28434843
TI  - Becoming a "Winning" Radiology Group in a Value-Based Medical Reimbursement
      System: A Summary of the ACR-RBMA Practice Leaders Forum 2017.

PMID- 28434844
TI  - Quality and Value of Subspecialty Reinterpretation of Thoracic CT Scans of
      Patients Referred to a Tertiary Cancer Center.
AB  - INTRODUCTION: Patients referred to tertiary cancer centers often present with
      imaging studies performed and interpreted at other health care institutions.
      Although reinterpretation of imaging performed at another health care institution
      can reduce repeat imaging, unnecessary radiation dose, and cost, the benefit is
      uncertain. The purpose of this study is to evaluate the quality of initial
      imaging studies of patients seeking a second opinion at a tertiary cancer center,
      to compare the accuracy of initial interpretations to reinterpretations performed
      by subspecialty trained radiologists at a tertiary oncologic center, and to
      determine the potential impact on patient management. METHODS: An institutional
      review board-approved retrospective, single-institution database review was
      performed in 120 new patients presenting to the thoracic surgery clinics at our
      institution from 2010 through 2013, with initial chest CTs performed at another
      institution. Two thoracic radiologists blinded to the interpretation
      independently assessed the quality and performed a reinterpretation of 52 CTs.
      Fisher's exact tests were used to compare the frequency with which clinically
      important staging parameters appeared in the reinterpretations and initial
      reports. Discrepancies between the reinterpretations and initial interpretations
      were adjudicated independently by two thoracic radiologists at different tertiary
      cancer institutions to determine which interpretations were more accurate. The
      impact of discrepancies on clinical management was evaluated based on National
      Comprehensive Cancer Network guidelines. RESULTS: Of the 52 CTs, 32 (62%) were of
      inadequate image quality for staging. In 17 of 52 (33%), discrepancies were
      identified between reinterpretations and initial interpretations. For
      discrepancies, the reinterpretation was judged to be more accurate for staging
      than the initial interpretation. In nine of these patients, staging parameters
      were omitted in the initial interpretations that precluded adequate staging. In
      the remaining eight patients, six were upstaged, one was downstaged, and one was
      unchanged by the reinterpretation. CONCLUSIONS: Imaging studies from outside
      institutions are of variable image quality and often not adequate for appropriate
      staging of thoracic malignancies. Reinterpretation can decrease repeat imaging
      and associated technical costs. Additionally, the accuracy of staging is improved
      by reinterpretation of CTs by subspecialty trained radiologists and can
      significantly impact clinical management.

PMID- 28434841
TI  - Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma.
AB  - Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited
      therapeutic options. The majority of cases of DIPG exhibit a mutation in histone
      3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here
      that DIPG is vulnerable to transcriptional disruption using bromodomain
      inhibition or CDK7 blockade. Targeting oncogenic transcription through either of
      these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC
      inhibitor therapy retain sensitivity to CDK7 blockade. Identification of super
      enhancers in DIPG provides insights toward the cell of origin, highlighting
      oligodendroglial lineage genes, and reveals unexpected mechanisms mediating tumor
      viability and invasion, including potassium channel function and EPH receptor
      signaling. The findings presented demonstrate transcriptional vulnerabilities and
      elucidate previously unknown mechanisms of DIPG pathobiology.

PMID- 28434845
TI  - ABR Subspecialty Certifications in Hospice and Palliative Medicine and Pain
      Medicine.
AB  - The ACGME currently approves fellowship training in 11 subspecialties of
      radiology, and the ABR currently offers six subspecialty certificates (vascular
      interventional radiology will be phased out in 2017) to its primary certificate
      holders. Four of the ABR-sponsored or co-sponsored subspecialties have been
      available to ABR diplomates for more than 18 years, but two-hospice and
      palliative medicine and pain medicine-are relatively new. The nature of specialty
      and subspecialty certificate development and details related to these two
      specific programs will be considered.

PMID- 28434846
TI  - Effect of an Automated Tracking Registry on the Rate of Tracking Failure in
      Incidental Pulmonary Nodules.
AB  - OBJECTIVE: Following incidental lung nodules with interval CT scanning is an
      accepted method to detect early lung cancer, but delayed tracking or failure to
      track is reported in up to 40% of patients. METHODS: Our institution developed
      and implemented an automated lung nodule registry tracking system. This system
      uses a code at the time that a suspicious nodule is discovered to populate the
      registry. Suspicious nodules were defined as any nodule, solid or ground glass,
      <3 cm that the radiologist recorded as a potential malignancy or recommended for
      follow-up imaging. We exported the system to eight other Veterans Administration
      Medical Centers (VAMCs) with over 10,000 patients enrolled. We retrospectively
      reviewed 200 sequential CT scan reports containing incidental nodule(s) from two
      tertiary care university-affiliated VAMCs, both before and after the
      implementation of the registry tracking system. The primary outcome was the rate
      of tracking failure, defined as suspicious nodules that had no follow-up imaging
      or whose follow-up was delayed when compared with published guidelines. Secondary
      outcomes were predictors of tracking failure and reasons for tracking failure.
      RESULTS: After implementation of the registry tracking system in the two VAMCs,
      we found a significant decrease in tracking failure, from a preimplementation
      rate of 74% to a postimplementation rate of 10% (P < .001). We found that age,
      nodule size, number, and nodule characteristics were significant predictors.
      CONCLUSIONS: The automated lung nodule registry tracking system can be exported
      to other health care facilities and significantly reduces the rate of tracking
      failure.

PMID- 28434847
TI  - MRI Before Radiography for Patients With New Shoulder Conditions.
AB  - PURPOSE: To assess the patterns of Appropriate Criteria application among
      orthopedic specialists and other fields of medicine for use of MRI and
      radiography and the subsequent necessity for surgical intervention. METHODS: The
      hospital electronic medical record was used to identify all shoulder MRI studies
      at a single large urban teaching hospital between January 2, 2011, and June 30,
      2011. For each study, variables collected included ordering department, patient
      age, patient gender, patient's self-reported race/ethnicity, whether the patient
      obtained surgery for an issue related to the MRI diagnosis, the type of MRI
      ordered, the date of pain onset, the date of x-ray (if any), and the date of the
      MRI. RESULTS: A total of 475 patients who underwent shoulder MRI were included in
      our study. We found significant associations between a patient having had a prior
      x-ray and ordering department (P < .0001), male gender (P = .0005), and subjects
      who had subsequent surgery (P = .0006). Neither age nor race and ethnicity had an
      influence on x-ray before MRI. Orthopedic specialists ordering MRIs had the
      highest percentage of patients undergo subsequent surgery (33.3%) compared with
      the second-most, primary care (18.4%), and all other ordering departments (P =
      .0009). CONCLUSIONS: Detailed analysis suggests that providers who do not have
      specific training in shoulder pathology should consider consultation with an
      orthopedic surgeon before ordering shoulder MRI for patients who may need
      additional imaging after radiography.

PMID- 28434848
TI  - Evaluating the Effect of Unstructured Clinical Information on Clinical Decision
      Support Appropriateness Ratings.
AB  - OBJECTIVE: To determine the appropriateness rating (AR) of advanced inpatient
      imaging requests that were not rated by prospective, point-of-care clinical
      decision support (CDS) using computerized provider order entry. MATERIALS AND
      METHODS: During 30-day baseline and intervention periods, CDS generated an AR for
      advanced inpatient imaging requests (nuclear medicine, CT, and MRI) using
      provider-selected structured indications from pull-down menus in the computerized
      provider order entry portal. The AR was only displayed during the intervention,
      and providers were required to acknowledge the AR to finalize the request.
      Subsequently, the unstructured free text information accompanying all requests
      was reviewed, and the AR was revised when possible. The percentage of unrated
      requests and the overall AR, before and after radiologist review, were compared
      between periods and by provider type. RESULTS: CDS software prospectively
      generated an AR for only 25.4% and 28.4% of baseline and intervention imaging
      requests, respectively; however, radiologist review generated an AR for 82.4% and
      93.6% of the same requests. During the respective periods, the percentage of
      baseline and intervention imaging requests considered appropriate was 18.7% and
      22.9% by prospective CDS software rating and increased to 82.4% and 88.7% with
      radiologist review. CONCLUSION: Despite limited effective use of CDS software,
      the percentage of requests containing additional, relevant clinical information
      increased, and the majority of requests had overall high appropriateness when
      reviewed by a radiologist. Additional work is needed to improve the amount and
      quality of clinical information available to CDS software and to facilitate the
      entry of this information by appropriate end users.

PMID- 28434849
TI  - Effective Radiology Reporting.

PMID- 28434850
TI  - Three Trillion and Counting.

PMID- 28434851
TI  - Long-term audit of platelet consumption in a university hospital.
AB  - OBJECTIVES: To determine the long-term trend in platelet consumption in a
      university hospital. MATERIALS AND METHODS: The annual consumption of platelets
      concentrate (PC) was analyzed over 23 years (1985-2007) in King Khalid University
      Hospital (KKUH), Riyadh, Saudi Arabia. RESULTS: The total 23 years consumption
      was 100,466 units of PC. Consumption went through 3 phases: the first, 1985-1994:
      the annual consumption increased from 1706 to 5912 which coincided with the
      increase in the number of patient admissions; the second, 1994-2003:featured a
      remarkable drop (48.9%) in annual consumption while patient admission remained
      stable. There was a concurrent decline in platelet consumption and all-cause
      mortality/patient. Third phase: 2003-2007, the consumption increased to reach
      5642 units/year in 2007. The Department of Medicine consumed (52%), followed by
      Pediatrics (21%), and General Surgery (16%). CONCLUSION: This audit uncovered
      evidence of inappropriate platelet consumption that reached 48.9% in the period
      1994 to 2003, which coincided with widely publicized HIV scare that dominated
      blood transfusion during that period. We also found evidence suggesting that
      reducing platelet transfusion could improve patient outcome.

PMID- 28434852
TI  - P. falciparum malaria prevalence among blood donors in Bamako, Mali.
AB  - AIM: Malaria parasite is usually transmitted to humans by Anopheles mosquitoes
      but it can also be transmitted through blood transfusion. Usually malaria
      transmission is low in African urban settings. In West Africa where the P.
      falciparum is the most predominant malaria species, there are limited measures to
      reduce the risk of blood transfusion malaria. The aim of this study was to
      evaluate the prevalence of P. falciparum malaria carriage among blood donors in
      the National Blood Center of Bamako, capital city of Mali. METHODS: The study was
      conducted using a random sample of 946 blood donors in Bamako, Mali, from January
      to December 2011. Screening for malaria was performed by thick smear and rapid
      diagnostic test (RDT). Blood group was typed by Beth-Vincent and Simonin
      techniques. RESULTS: The frequency of malaria infection was 1.4% by thick smear
      and 0.8% by the RDT. The pick prevalence of P. falciparum malaria was in rainy
      season, indicating a probable high seasonal risk of malaria by blood transfusion,
      in Mali. The prevalence of P. falciparum infection was 2% among donors of group O
      the majority being in this group. CONCLUSION: There is a seasonal prevalence of
      malaria among blood donors in Bamako. A prevention strategy of transfusion
      malaria based on the combination of selection of blood donors through the medical
      interview, promoting a voluntary low-risk blood donation and screening all blood
      bags intended to be transfused to children under 5, pregnant women and immune
      compromised patients during transmission season using thick smear will reduce the
      risk of transfusion malaria in Mali.

PMID- 28434853
TI  - Interhospital transfers of a mobile team for organ preservation with
      extracorporeal membrane oxygenation in controlled donors after circulatory death.

PMID- 28434854
TI  - Opportunistic autoimmunity secondary to immunotherapy and melanoma: Back to
      ABCDE?

PMID- 28434855
TI  - Health-care use before a first demyelinating event suggestive of a multiple
      sclerosis prodrome: a matched cohort study.
AB  - BACKGROUND: Degenerative processes in neurodegenerative diseases can start years
      before clinical manifestation. We aimed to establish whether a multiple sclerosis
      prodromal period exists by examining patterns of health-care use before a first
      demyelinating event. METHODS: In this matched cohort study, we used data from
      linked health administrative and clinical databases from four Canadian provinces
      (British Columbia, Saskatchewan, Manitoba, and Nova Scotia) to compare hospital,
      physician, and prescription use data from people with multiple sclerosis and
      matched general population controls in the 5 years before the first demyelinating
      disease claim (health administrative index date) or clinically reported symptom
      onset (clinical index date). Rate ratios (RRs) were estimated using negative
      binomial regression and combined across provinces using random effect models. The
      primary outcome was all-cause use of health care during each of the 5 years
      before the health administrative or clinical index date. FINDINGS: The health
      administrative cohort included 14 428 multiple sclerosis cases and 72 059 matched
      controls for whom data were available between April, 1984, and April, 2014.
      Annual health-care use increased steadily between 5 years and 1 year before the
      first demyelinating disease claim in people with multiple sclerosis compared with
      controls (from RR 1.26 [95% CI 1.16-1.36] to 1.78 [1.50-2.10] for hospital
      admissions; from 1.24 [1.16-1.32] to 1.88 [1.72-2.07] for physician claims; and
      from 1.23 [1.06-1.41] to 1.49 [1.41-1.59] for prescriptions, assessed as drug
      classes). Similar patterns for physician claims and prescriptions were observed
      in the cohort with available clinical symptom onset (3202 individuals with
      multiple sclerosis and 16 006 controls), although the differences in use in each
      of the 5 years mostly did not reach statistical significance. INTERPRETATION:
      More frequent use of health care in patients with multiple sclerosis than in
      controls in the 5 years before a first demyelinating event, according to health
      administrative data, suggests the existence of a measurable multiple sclerosis
      prodrome. These findings have clinical and research implications, including the
      establishment of an earlier window of opportunity to identify and potentially
      treat multiple sclerosis. FUNDING: National Multiple Sclerosis Society.

PMID- 28434856
TI  - Can CT and MR Shape and Textural Features Differentiate Benign Versus Malignant
      Pleural Lesions?
AB  - RATIONALE AND OBJECTIVES: The study aimed to identify a radiomic approach based
      on CT and or magnetic resonance (MR) features (shape and texture) that may help
      differentiate benign versus malignant pleural lesions, and to assess if the
      radiomic model may improve confidence and accuracy of radiologists with different
      subspecialty backgrounds. MATERIALS AND METHODS: Twenty-nine patients with
      pleural lesions studied on both contrast-enhanced CT and MR imaging were reviewed
      retrospectively. Three texture and three shape features were extracted.
      Combinations of features were used to generate logistic regression models using
      histopathology as outcome. Two thoracic and two abdominal radiologists evaluated
      their degree of confidence in malignancy. Diagnostic accuracy of radiologists was
      determined using contingency tables. Cohen's kappa coefficient was used to assess
      inter-reader agreement. Using optimal threshold criteria, sensitivity,
      specificity, and accuracy of each feature and combination of features were
      obtained and compared to the accuracy and confidence of radiologists. RESULTS:
      The CT model that best discriminated malignant from benign lesions revealed an
      AUCCT = 0.92 +/- 0.05 (P < 0.0001). The most discriminative MR model showed an
      AUCMR = 0.87 +/- 0.09 (P < 0.0001). The CT model was compared to the diagnostic
      confidence of all radiologists and the model outperformed both abdominal
      radiologists (P < 0.002), whereas the top discriminative MR model outperformed
      one of the abdominal radiologists (P = 0.02). The most discriminative MR model
      was more accurate than one abdominal (P = 0.04) and one thoracic radiologist (P =
      0.02). CONCLUSION: Quantitative textural and shape analysis may help distinguish
      malignant from benign lesions. A radiomics-based approach may increase diagnostic
      confidence of abdominal radiologists on CT and MR and may potentially improve
      radiologists' accuracy in the assessment of pleural lesions characterized by MR.

PMID- 28434857
TI  - A study evaluating the postprandial plasma glucose control among type 2 diabetes
      patients attending a teaching hospital in Malaysia.
AB  - BACKGROUND AND OBJECTIVE: Type 2 DM is rapidly rising as a global health care
      problem that threatens to reach pandemic levels by 2030. Type 2 diabetes mellitus
      is a disease with no cure and chronic disease that results in major morbidity and
      mortality. The main objective of this study is to evaluate postprandial plasma
      glucose level and to determine factors affect on postprandial plasma glucose
      level among type 2 diabetes outpatients attending endocrinology clinics at
      Hospital Universiti Sains Malaysia, Teaching Hospital. SUBJECTS AND METHODS: The
      study design was observational prospective longitudinal follow-up study, the
      study was conducted with sample of 1077 type 2 diabetes mellitus outpatient
      recruited via attended the diabetes clinics at Hospital Universiti Sains Malaysia
      (HUSM) in Kelantan. Post prandial plasma glucose (PPG) parameter to measure the
      glycaemic control. Logistic regression analysis was used to assess the
      independent variables that affect the PPG control. RESULTS: About 426 (39.6%) of
      the patients did not achieve the optimal postprandial plasma glucose level
      (<10mmol/l). In this study, the possible factors that affect postprandial plasma
      glucose levels (PPG) were found to be gender (OR=0.77) and the duration of
      diabetes (OR=1.12). CONCLUSION: It has been found that gender and the duration of
      diabetes are the factors affecting PPG. New strategy to improve the current
      status of control of diabetes is needed. The study recommends that health-care
      providers should pay more attention to type 2 DM male patients and patients who
      had diabetic for long time.

PMID- 28434858
TI  - Stem Cell-Intrinsic, Seven-up-Triggered Temporal Factor Gradients Diversify
      Intermediate Neural Progenitors.
AB  - Building a sizable, complex brain requires both cellular expansion and
      diversification. One mechanism to achieve these goals is production of multiple
      transiently amplifying intermediate neural progenitors (INPs) from a single
      neural stem cell. Like mammalian neural stem cells, Drosophila type II
      neuroblasts utilize INPs to produce neurons and glia. Within a given lineage, the
      consecutively born INPs produce morphologically distinct progeny, presumably due
      to differential inheritance of temporal factors. To uncover the underlying
      temporal fating mechanisms, we profiled type II neuroblasts' transcriptome across
      time. Our results reveal opposing temporal gradients of Imp and Syp RNA-binding
      proteins (descending and ascending, respectively). Maintaining high Imp
      throughout serial INP production expands the number of neurons and glia with
      early temporal fate at the expense of cells with late fate. Conversely,
      precocious upregulation of Syp reduces the number of cells with early fate.
      Furthermore, we reveal that the transcription factor Seven-up initiates
      progression of the Imp/Syp gradients. Interestingly, neuroblasts that maintain
      initial Imp/Syp levels can still yield progeny with a small range of early fates.
      We therefore propose that the Seven-up-initiated Imp/Syp gradients create coarse
      temporal windows within type II neuroblasts to pattern INPs, which subsequently
      undergo fine-tuned subtemporal patterning.

PMID- 28434859
TI  - Tissue-Specific Emission of (E)-alpha-Bergamotene Helps Resolve the Dilemma When
      Pollinators Are Also Herbivores.
AB  - More than 87% of flowering plant species are animal-pollinated [1] and produce
      floral scents and other signals to attract pollinators. These floral cues may
      however also attract antagonistic visitors, including herbivores [2]. The dilemma
      is exacerbated when adult insects pollinate the same plant that their larvae
      consume. It remains largely unclear how plants maximize their fitness under these
      circumstances. Here we show that in the night-flowering wild tobacco Nicotiana
      attenuata, the emission of a sesquiterpene, (E)-alpha-bergamotene, in flowers
      increases adult Manduca sexta moth-mediated pollination success, while the same
      compound in leaves is known to mediate indirect defense against M. sexta larvae
      [3, 4]. Forward and reverse genetic analyses demonstrated that both herbivory
      induced and floral (E)-alpha-bergamotene are regulated by the expression of a
      monoterpene-synthase-derived sesquiterpene synthase (NaTPS38). The expression
      pattern of NaTPS38 also accounts for variation in (E)-alpha-bergamotene emission
      among natural accessions. These results highlight that differential expression of
      a single gene that results in tissue-specific emission of one compound
      contributes to resolving the dilemma for plants when their pollinators are also
      herbivores. Furthermore, this study provides genetic evidence that pollinators
      and herbivores interactively shape the evolution of floral signals and plant
      defense.

PMID- 28434860
TI  - Direct Brain Stimulation Modulates Encoding States and Memory Performance in
      Humans.
AB  - People often forget information because they fail to effectively encode it. Here,
      we test the hypothesis that targeted electrical stimulation can modulate neural
      encoding states and subsequent memory outcomes. Using recordings from
      neurosurgical epilepsy patients with intracranially implanted electrodes, we
      trained multivariate classifiers to discriminate spectral activity during
      learning that predicted remembering from forgetting, then decoded neural activity
      in later sessions in which we applied stimulation during learning. Stimulation
      increased encoding-state estimates and recall if delivered when the classifier
      indicated low encoding efficiency but had the reverse effect if stimulation was
      delivered when the classifier indicated high encoding efficiency. Higher encoding
      state estimates from stimulation were associated with greater evidence of neural
      activity linked to contextual memory encoding. In identifying the conditions
      under which stimulation modulates memory, the data suggest strategies for
      therapeutically treating memory dysfunction.

PMID- 28434861
TI  - Representation of Multiple Body Parts in the Missing-Hand Territory of Congenital
      One-Handers.
AB  - Individuals born without one hand (congenital one-handers) provide a unique model
      for understanding the relationship between focal reorganization in the
      sensorimotor cortex and everyday behavior. We previously reported that the
      missing hand's territory of one-handers becomes utilized by its cortical neighbor
      (residual arm representation), depending on residual arm usage in daily life to
      substitute for the missing hand's function [1, 2]. However, the repertoire of
      compensatory behaviors may involve utilization of other body parts that do not
      cortically neighbor the hand territory. Accordingly, the pattern of brain
      reorganization may be more extensive [3]. Here we studied unconstrained
      compensatory strategies under ecological conditions in one-handers, as well as
      changes in activation, connectivity, and neurochemical profile in their missing
      hand's cortical territory. We found that compensatory behaviors in one-handers
      involved multiple body parts (residual arm, lips, and feet). This diversified
      compensatory profile was associated with large-scale cortical reorganization,
      regardless of cortical proximity to the hand territory. Representations of those
      body parts used to substitute hand function all mapped onto the cortical
      territory of the missing hand, as evidenced by task-based and resting-state fMRI.
      The missing-hand territory also exhibited reduced GABA levels, suggesting a
      reduction in connectional selectivity to enable the expression of diverse
      cortical inputs. Because the same body parts used for compensatory purposes are
      those showing increased representation in the missing hand's territory, we
      suggest that the typical hand territory may not necessarily represent the hand
      per se, but rather any other body part that shares the functionality of the
      missing hand [4].

PMID- 28434862
TI  - Consequences of the Oculomotor Cycle for the Dynamics of Perception.
AB  - Much evidence indicates that humans and other species process large-scale visual
      information before fine spatial detail. Neurophysiological data obtained with
      paralyzed eyes suggest that this coarse-to-fine sequence results from
      spatiotemporal filtering by neurons in the early visual pathway. However, the
      eyes are normally never stationary: rapid gaze shifts (saccades) incessantly
      alternate with slow fixational movements. To investigate the consequences of this
      oculomotor cycle on the dynamics of perception, we combined spectral analysis of
      visual input signals, neural modeling, and gaze-contingent control of retinal
      stimulation in humans. We show that the saccade/fixation cycle reformats the flow
      impinging on the retina in a way that initiates coarse-to-fine processing at each
      fixation. This finding reveals that the visual system uses oculomotor-induced
      temporal modulations to sequentially encode different spatial components and
      suggests that, rather than initiating coarse-to-fine processing, spatiotemporal
      coupling in the early visual pathway builds on the information dynamics of the
      oculomotor cycle.

PMID- 28434863
TI  - Spatiotemporally Controlled Mechanical Cues Drive Progenitor Mesenchymal-to
      Epithelial Transition Enabling Proper Heart Formation and Function.
AB  - During early cardiogenesis, bilateral fields of mesenchymal heart progenitor
      cells (HPCs) move from the anterior lateral plate mesoderm to the ventral
      midline, undergoing a mesenchymal-to-epithelial transition (MET) en route to
      forming a single epithelial sheet. Through tracking of tissue-level deformations
      in the heart-forming region (HFR) as well as movement trajectories and traction
      generation of individual HPCs, we find that the onset of MET correlates with a
      peak in mechanical stress within the HFR and changes in HPC migratory behaviors.
      Small-molecule inhibitors targeting actomyosin contractility reveal a temporally
      specific requirement of bulk tissue compliance to regulate heart development and
      MET. Targeting mutant constructs to modulate contractility and compliance in the
      underlying endoderm, we find that MET in HPCs can be accelerated in response to
      microenvironmental stiffening and can be inhibited by softening. To test whether
      MET in HPCs was responsive to purely physical mechanical cues, we mimicked a high
      stress state by injecting an inert oil droplet to generate high strain in the
      HFR, demonstrating that exogenously applied stress was sufficient to drive MET.
      MET-induced defects in anatomy result in defined functional lesions in the larval
      heart, implicating mechanical signaling and MET in the etiology of congenital
      heart defects. From this integrated analysis of HPC polarity and mechanics, we
      propose that normal heart development requires bilateral HPCs to undergo a
      critical behavioral and phenotypic transition on their way to the ventral
      midline, and that this transition is driven in response to the changing
      mechanical properties of their endoderm substrate.

PMID- 28434864
TI  - Sensorimotor Representations in Cerebellar Granule Cells in Larval Zebrafish Are
      Dense, Spatially Organized, and Non-temporally Patterned.
AB  - A fundamental question in neurobiology is how animals integrate external sensory
      information from their environment with self-generated motor and sensory signals
      in order to guide motor behavior and adaptation. The cerebellum is a vertebrate
      hindbrain region where all of these signals converge and that has been implicated
      in the acquisition, coordination, and calibration of motor activity. Theories of
      cerebellar function postulate that granule cells encode a variety of sensorimotor
      signals in the cerebellar input layer. These models suggest that representations
      should be high-dimensional, sparse, and temporally patterned. However, in vivo
      physiological recordings addressing these points have been limited and in
      particular have been unable to measure the spatiotemporal dynamics of population
      wide activity. In this study, we use both calcium imaging and electrophysiology
      in the awake larval zebrafish to investigate how cerebellar granule cells encode
      three types of sensory stimuli as well as stimulus-evoked motor behaviors. We
      find that a large fraction of all granule cells are active in response to these
      stimuli, such that representations are not sparse at the population level. We
      find instead that most responses belong to only one of a small number of distinct
      activity profiles, which are temporally homogeneous and anatomically clustered.
      We furthermore identify granule cells that are active during swimming behaviors
      and others that are multimodal for sensory and motor variables. When we
      pharmacologically change the threshold of a stimulus-evoked behavior, we observe
      correlated changes in these representations. Finally, electrophysiological data
      show no evidence for temporal patterning in the coding of different stimulus
      durations.

PMID- 28434865
TI  - Allergens involved in the cross-reactivity of Aedes aegypti with other
      arthropods.
AB  - BACKGROUND: Cross-reactivity between Aedes aegypti and mites, cockroaches, and
      shrimp has been previously suggested, but the involved molecular components have
      not been fully described. OBJECTIVE: To evaluate the cross-reactivity between A
      aegypti and other arthropods. METHODS: Thirty-four serum samples from patients
      with asthma and/or allergic rhinitis were selected, and specific IgE to A
      aegypti, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia
      tropicalis, Periplaneta americana. and Litopenaeus vannamei was measured by
      enzyme-linked immunosorbent assay. Cross-reactivity was investigated using pooled
      serum samples from allergic patients, allergenic extracts, and the recombinant
      tropomyosins (Aed a 10.0201, Der p 10, Blo t 10, Lit v 1, and Per a 7). Four IgE
      reactive bands were further characterized by matrix-assisted laser
      desorption/ionization tandem time of flight. RESULTS: Frequency of positive IgE
      reactivity was 82.35% to at least one mite species, 64.7% to A aegypti, 29.4% to
      P americana, and 23.5% to L vannamei. The highest IgE cross-reactivity was seen
      between A aegypti and D pteronyssinus (96.6%) followed by L vannamei (95.4%), B
      tropicalis (84.4%), and P americana (75.4%). Recombinant tropomyosins from mites,
      cockroach, or shrimp inhibited the IgE reactivity to the mosquito at a lower
      extent than the extracts from these arthropods. Several bands of A aegypti cross
      reacted with arthropod extracts, and 4 of them were identified as odorant binding
      protein, mitochondrial cytochrome C, peptidyl-prolyl cis-trans isomerase, and
      protein with hypothetical magnesium ion binding function. CONCLUSION: We
      identified 4 novel cross-reactive allergens in A aegypti allergenic extract.
      These molecules could influence the manifestation of allergy to environmental
      allergens in the tropics.

PMID- 28434867
TI  - Two Decades of ASGCT: Dreams Become Reality.

PMID- 28434866
TI  - Lentiviral Vectors with Cellular Promoters Correct Anemia and Lethal Bone Marrow
      Failure in a Mouse Model for Diamond-Blackfan Anemia.
AB  - Diamond-Blackfan anemia is a congenital erythroid hypoplasia and is associated
      with physical malformations and a predisposition to cancer. Twenty-five percent
      of patients with Diamond-Blackfan anemia have mutations in a gene encoding
      ribosomal protein S19 (RPS19). Through overexpression of RPS19 using a lentiviral
      vector with the spleen focus-forming virus promoter, we demonstrated that the
      Diamond-Blackfan anemia phenotype can be successfully treated in Rps19-deficient
      mice. In our present study, we assessed the efficacy of a clinically relevant
      promoter, the human elongation factor 1alpha short promoter, with or without the
      locus control region of the beta-globin gene for treatment of RPS19-deficient
      Diamond-Blackfan anemia. The findings demonstrate that these vectors rescue the
      proliferation defect and improve erythroid development of transduced RPS19
      deficient bone marrow cells. Remarkably, bone marrow failure and severe anemia in
      Rps19-deficient mice was cured with enforced expression of RPS19 driven by the
      elongation factor 1alpha short promoter. We also demonstrate that RPS19-deficient
      bone marrow cells can be transduced and these cells have the capacity to
      repopulate bone marrow in long-term reconstituted mice. Our results collectively
      demonstrate the feasibility to cure RPS19-deficient Diamond-Blackfan anemia using
      lentiviral vectors with cellular promoters that possess a reduced risk of
      insertional mutagenesis.

PMID- 28434869
TI  - Worms on the spectrum - C. elegans models in autism research.
AB  - The small non-parasitic nematode Caenorhabditis elegans is widely used in
      neuroscience thanks to its well-understood development and lineage of the nervous
      system. Furthermore, C. elegans has been used to model many human developmental
      and neurological conditions to better understand disease mechanisms and identify
      potential therapeutic strategies. Autism spectrum disorder (ASD) is the most
      prevalent of all neurodevelopmental disorders, and the C. elegans system may
      provide opportunities to learn more about this complex disorder. Since basic cell
      biology and biochemistry of the C. elegans nervous system is generally very
      similar to mammals, cellular or molecular phenotypes can be investigated, along
      with a repertoire of behaviours. For instance, worms have contributed greatly to
      the understanding of mechanisms underlying mutations in genes coding for synaptic
      proteins such as neuroligin and neurexin. Using worms to model neurodevelopmental
      disorders like ASD is an emerging topic that harbours great, untapped potential.
      This review summarizes the numerous contributions of C. elegans to the field of
      neurodevelopment and introduces the nematode system as a potential research tool
      to study essential roles of genes associated with ASD.

PMID- 28434868
TI  - HIF-1alpha Dependent Wound Healing Angiogenesis In Vivo Can Be Controlled by Site
      Specific Lentiviral Magnetic Targeting of SHP-2.
AB  - Hypoxia promotes vascularization by stabilization and activation of the hypoxia
      inducible factor 1alpha (HIF-1alpha), which constitutes a target for angiogenic
      gene therapy. However, gene therapy is hampered by low gene delivery efficiency
      and non-specific side effects. Here, we developed a gene transfer technique based
      on magnetic targeting of magnetic nanoparticle-lentivirus (MNP-LV) complexes
      allowing site-directed gene delivery to individual wounds in the dorsal skin of
      mice. Using this technique, we were able to control HIF-1alpha dependent wound
      healing angiogenesis in vivo via site-specific modulation of the tyrosine
      phosphatase activity of SHP-2. We thus uncover a novel physiological role of SHP
      2 in protecting HIF-1alpha from proteasomal degradation via a Src kinase
      dependent mechanism, resulting in HIF-1alpha DNA-binding and transcriptional
      activity in vitro and in vivo. Excitingly, using targeting of MNP-LV complexes,
      we achieved simultaneous expression of constitutively active as well as inactive
      SHP-2 mutant proteins in separate wounds in vivo and hereby specifically and
      locally controlled HIF-1alpha activity as well as the angiogenic wound healing
      response in vivo. Therefore, magnetically targeted lentiviral induced modulation
      of SHP-2 activity may be an attractive approach for controlling patho
      physiological conditions relying on hypoxic vessel growth at specific sites.

PMID- 28434872
TI  - The use of emergency department-based psychological interventions to reduce
      repetition of self-harm behaviour.

PMID- 28434871
TI  - A brief psychological intervention to reduce repetition of self-harm in patients
      admitted to hospital following a suicide attempt: a randomised controlled trial.
AB  - BACKGROUND: We investigated whether a volitional helpsheet (VHS), a brief
      psychological intervention, could reduce repeat self-harm in the 6 months
      following a suicide attempt. METHODS: We did a prospective, single-site,
      randomised controlled trial. Patients admitted to a hospital in Edinburgh, UK,
      after a suicide attempt were deemed eligible for the study if they were over the
      age of 16 years, had a self-reported history of self-harm, were fluent in
      English, were medically fit to interview, and were not participating in other
      research studies within the hospital. Eligible patients were randomly assigned
      (1:1), via web-based randomisation, to receive either VHS plus usual treatment
      (intervention group) or only treatment as usual (control group). Randomisation
      was stratified by sex and self-reported past self-harm history. The Information
      Services Division of the National Health Service (NHS-ISD) staff and those
      extracting data from medical notes were masked to the study group the participant
      was allocated to. Clinical staff working within the hospital were also masked to
      participants' randomisation status. There were three primary outcomes: the
      proportion of paticipants who re-presented to hospital with self-harm during the
      6-month follow-up period; the number of times a participant re-presented to
      hospital with self-harm during the 6-month follow-up period; and cost
      effectiveness of the VHS as measured by estimated incremental cost per self-harm
      event averted. Primary outcomes were analysed in all randomised patients. Follow
      up data collection was extracted from the Information Services Division of the
      NHS and from patient medical records. The trial is registered with International
      Standard Randomised Controlled Trial Number Registry, number ISRCTN99488269.
      FINDINGS: Between May 9, 2012, and Feb 24, 2014, we assessed 1308 people for
      eligibility. Of these, 259 patients were randomly assigned to the intervention
      group and 259 to the control group. We obtained complete follow-up data on 512
      (99%) of 518 patients (five participants were lost to follow-up in the
      intervention group and one in the control group). 11 patients assigned to the
      intervention group did not complete the VHS in hospital. Overall, the
      intervention did not affect the number of people who re-presented with self-harm
      (67 [26%] of 254 patients in the intervention group vs 71 [28%] of 258 patients
      in the control group, odds ratio [OR] 0.90, 95% CI 0.58-1.39, p=0.63). The
      intervention had no effect on the number of re-presentations per patient (mean
      0.67 [SD 2.55] re-presentations for the intervention group vs 0.85 [2.79] for the
      control group, incident rate ratio [IRR] 1.65, 95% CI 0.74-3.67, p=0.21). Mean
      total costs per person for NHS hospital services in the VHS intervention group
      over the 6 months were L513 versus L561 in the control group but this difference
      was not significant (95% CI-L353 to L257, p=0.76). Three patients died by suicide
      in the 6 months following their index suicide attempt (one in the intervention
      group and two in the control group). There were no reported unintended effects or
      adverse events in either group. INTERPRETATION: For the primary outcomes, there
      were no significant differences between groups. Although the VHS had no overall
      effect, post-hoc analyses suggest VHS might be effective in reducing the number
      of self-harm repetitions following a suicide attempt in people who complete the
      helpsheet and who have been previously admitted to hospital with self-harm. This
      is the first study to investigate the usefulness of the VHS to reduce self-harm
      among those who have attempted suicide. These subgroup findings require
      replication. The potential use of the VHS in those who self-harm for different
      motives requires further exploration. FUNDING: Chief Scientist Office
      (CZH/4/704).

PMID- 28434870
TI  - Maternal socioeconomic disadvantage is associated with transcriptional
      indications of greater immune activation and slower tissue maturation in
      placental biopsies and newborn cord blood.
AB  - Children from economically disadvantaged families experience worse cognitive,
      psychiatric, and medical outcomes compared to more affluent youth. Preclinical
      models suggest some of the adverse influence of disadvantage could be transmitted
      during gestation via maternal immune activation, but this hypothesis has not been
      tested in humans. It also remains unclear whether prenatal interventions can
      mitigate such effects. To fill these gaps, we conducted two studies. Study 1
      characterized the socioeconomic conditions of 79 women during pregnancy. At
      delivery, placenta biopsies and umbilical blood were collected for
      transcriptional profiling. Maternal disadvantage was associated with a
      transcriptional profile indicative of higher immune activation and slower fetal
      maturation, particularly in pathways related to brain, heart, and immune
      development. Cord blood cells of disadvantaged newborns also showed indications
      of immaturity, as reflected in down-regulation of pathways that coordinate
      myeloid cell development. These associations were independent of fetal sex, and
      characteristics of mothers (age, race, adiposity, diabetes, pre-eclampsia) and
      babies (delivery method, gestational age). Study 2 performed the same
      transcriptional analyses in specimens from 20 women participating in
      CenteringPregnancy, a group-based psychosocial intervention, and 20 women in
      traditional prenatal care. In both placenta biopsies and cord blood, women in
      CenteringPregnancy showed up-regulation of transcripts found in Study 1 to be
      most down-regulated in conjunction with disadvantage. Collectively, these results
      suggest socioeconomic disparities in placental biology are evident at birth, and
      provide clues about the mechanistic origins of health disparities. They also
      suggest the possibility that psychosocial interventions could have mitigating
      influences.

PMID- 28434873
TI  - Editorial.

PMID- 28434874
TI  - Unusual isolated pelvic metastasis from a clear cell hepatocellular carcinoma
      demonstrated on 18F-FDG PET/CT after liver transplantation.

PMID- 28434875
TI  - Covalent Protein Labeling at Glutamic Acids.
AB  - Covalent labeling of amino acids in proteins by reactive small molecules, in
      particular at cysteine SH and lysine NH groups, is a powerful approach to
      identify and characterize proteins and their functions. However, for the less
      reactive carboxylic acids present in Asp and Glu, hardly any methodology is
      available. Employing the lipoprotein binding chaperone PDE6delta as an example,
      we demonstrate that incorporation of isoxazolium salts that resemble the
      structure and reactivity of Woodward's reagent K into protein ligands provides a
      novel method for selective covalent targeting of binding site carboxylic acids in
      whole proteomes. Covalent adduct formation occurs via rapid formation of enol
      esters and the covalent bond is stable even in the presence of strong
      nucleophiles. This new method promises to open up hitherto unexplored
      opportunities for chemical biology research.

PMID- 28434877
TI  - One Enzyme, Three Metabolites: Shewanella algae Controls Siderophore Production
      via the Cellular Substrate Pool.
AB  - Shewanella algae B516 produces avaroferrin, an asymmetric hydroxamate
      siderophore, which has been shown to inhibit swarming motility of Vibrio
      alginolyticus. We aimed to elucidate the biosynthesis of this siderophore and to
      investigate how S. algae coordinates the production of avaroferrin and its two
      symmetric counterparts. We reconstituted the reaction in vitro with the main
      enzyme AvbD and the putative biosynthetic precursors, and demonstrate that
      multispecificity of this enzyme results in the production of all three cyclic
      hydroxamate siderophores that were previously isolated as natural products from
      S. algae. Surprisingly, purified AvbD exhibited a clear preference for the larger
      cadaverine-derived substrate. In live cells, however, siderophore ratios are
      maximized toward avaroferrin production, and we demonstrate that these
      siderophore ratios are the result of a regulation on substrate pool level, which
      may allow rapid evolutionary adaptation to environmental changes. Our results
      thereby give insights into a unique evolutionary strategy toward metabolite
      diversity.

PMID- 28434876
TI  - Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN
      Riboswitch Disrupt Riboflavin Homeostasis in an Infectious Setting.
AB  - Riboswitches are bacterial-specific, broadly conserved, non-coding RNA structural
      elements that control gene expression of numerous metabolic pathways and
      transport functions essential for cell growth. As such, riboswitch inhibitors
      represent a new class of potential antibacterial agents. Recently, we identified
      ribocil-C, a highly selective inhibitor of the flavin mononucleotide (FMN)
      riboswitch that controls expression of de novo riboflavin (RF, vitamin B2)
      biosynthesis in Escherichia coli. Here, we provide a mechanistic characterization
      of the antibacterial effects of ribocil-C as well as of roseoflavin (RoF), an
      antimetabolite analog of RF, among medically significant Gram-positive bacteria,
      including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus
      faecalis. We provide genetic, biophysical, computational, biochemical, and
      pharmacological evidence that ribocil-C and RoF specifically inhibit dual FMN
      riboswitches, separately controlling RF biosynthesis and uptake processes
      essential for MRSA growth and pathogenesis. Such a dual-targeting mechanism is
      specifically required to develop broad-spectrum Gram-positive antibacterial
      agents targeting RF metabolism.

PMID- 28434878
TI  - Molecular Phenotyping Combines Molecular Information, Biological Relevance, and
      Patient Data to Improve Productivity of Early Drug Discovery.
AB  - Today, novel therapeutics are identified in an environment which is intrinsically
      different from the clinical context in which they are ultimately evaluated. Using
      molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show
      that by quantifying pathway reporter gene expression, molecular phenotyping can
      cluster compounds based on pathway profiles and dissect associations between
      pathway activities and disease phenotypes simultaneously. Molecular phenotyping
      was applicable to compounds with a range of binding specificities and triaged
      false positives derived from high-content screening assays. The technique
      identified a class of calcium-signaling modulators that can reverse disease
      regulated pathways and phenotypes, which was validated by structurally distinct
      compounds of relevant classes. Our results advocate for application of molecular
      phenotyping in early drug discovery, promoting biological relevance as a key
      selection criterion early in the drug development cascade.

PMID- 28434879
TI  - Sonoluminescence and acoustic emission spectra at different stages of cavitation
      zone development.
AB  - The way in which a cavitation zone develops in a focused pulsed ultrasound field
      is studied in this work. Sonoluminescence (SL), total hydrophone output and
      cavitation noise spectra have been recorded across a gradual, smooth increase in
      applied voltage. It is shown that the cavitation zone passes through a number of
      stages of evolution, according to increasing ultrasound intensity, decreasing
      pulse period and increasing ultrasound pulse duration. Sonoluminescence is absent
      in the first phase and the hydrophone output spectra consists of a main line with
      two or three harmonics whose intensity is much lower than that of the main
      (fundamental) line. The second stage sees the onset of SL whose intensity
      increases smoothly and is accompanied by the appearance of higher harmonics and
      subharmonics in the cavitation noise spectra. In some cases, the wide-band (WBN)
      component can be seen in noise spectra during the final part of the second stage.
      In the third stage, SL intensity increases significantly and often quite sharply,
      while WBN intensity increases in the same manner. This is accompanied by a
      synchronous increase in the absorption of ultrasound by the cavitation zone,
      which is manifested in a sharp decrease in the hydrophone output. In the fourth
      stage, both SL and WBN intensities tend to decrease despite the increased voltage
      applied to the transducer. Furthermore, the fundamental line tends to decrease in
      strength as well, despite the increasing ultrasound intensity. The obtained
      results clearly identify the different stages of cavitation zone development
      using cavitation noise spectra analyses. We then hypothesize that three of the
      above stages may be responsible for three known types of ultrasound action on
      biological cells: damping viability, reversible cell damage (sonoporation) and
      irreversible damage/cytotoxicity.

PMID- 28434880
TI  - Ultrasound-assisted extraction of rare-earth elements from carbonatite rocks.
AB  - In view of the increasing demand for rare-earth elements (REE) in many areas of
      high technology, alternative methods for the extraction of these elements have
      been developed. In this work, a process based on the use of ultrasound for the
      extraction of REE from carbonatite (an igneous rock) is proposed to avoid the use
      of concentrated reagents, high temperature and excessive extraction time. In this
      pioneer work for REE extraction from carbonatite rocks in a preliminary
      investigation, ultrasonic baths, cup horn systems or ultrasound probes operating
      at different frequencies and power were evaluated. In addition, the power
      released to the extraction medium and the ultrasound amplitude were also
      investigated and the temperature and carbonatite mass/volume of extraction
      solution ratio were optimized to 70 degrees C and 20mg/mL, respectively. Better
      extraction efficiencies (82%) were obtained employing an ultrasound probe
      operating at 20kHz for 15min, ultrasound amplitude of 40% (692Wdm-3) and using a
      diluted extraction solution (3% v/v HNO3+2% v/v HCl). It is important to mention
      that high extraction efficiency was obtained even using a diluted acid mixture
      and relatively low temperature in comparison to conventional extraction methods
      for REE. A comparison of results with those obtained by mechanical stirring
      (500rpm) using the same conditions (time, temperature and extraction solution)
      was carried out, showing that the use of ultrasound increased the extraction
      efficiency up to 35%. Therefore, the proposed ultrasound-assisted procedure can
      be considered as a suitable alternative for high efficiency extraction of REE
      from carbonatite rocks.

PMID- 28434882
TI  - A potential impact of Helicobacter pylori infection on both obstructive sleep
      apnea and atrial fibrillation-related stroke.

PMID- 28434881
TI  - Muramyl Dipeptide-Based Postbiotics Mitigate Obesity-Induced Insulin Resistance
      via IRF4.
AB  - Intestinal dysbiosis contributes to obesity and insulin resistance, but
      intervening with antibiotics, prebiotics, or probiotics can be limited by
      specificity or sustained changes in microbial composition. Postbiotics include
      bacterial components such as lipopolysaccharides, which have been shown to
      promote insulin resistance during metabolic endotoxemia. We found that bacterial
      cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic
      that requires NOD2. Injecting MDP lowered adipose inflammation and reduced
      glucose intolerance in obese mice without causing weight loss or altering the
      composition of the microbiome. MDP reduced hepatic insulin resistance during
      obesity and low-level endotoxemia. NOD1-activating muropeptides worsened glucose
      tolerance. IRF4 distinguished opposing glycemic responses to different types of
      peptidoglycan and was required for MDP/NOD2-induced insulin sensitization and
      lower metabolic tissue inflammation during obesity and endotoxemia. IRF4 was
      dispensable for exacerbated glucose intolerance via NOD1. Mifamurtide, an MDP
      based drug with orphan drug status, was an insulin sensitizer at clinically
      relevant doses in obese mice.

PMID- 28434883
TI  - Erratum.

PMID- 28434884
TI  - Neurotoxicity Outcomes in a Population-based Cohort of Elderly Patients Treated
      With Adjuvant Oxaliplatin for Colorectal Cancer.
AB  - BACKGROUND: The addition of oxaliplatin to adjuvant treatment regimens for
      colorectal cancer has been shown to improve overall survival at the expense of
      increased toxicity. The incidence and severity of toxicity might be greater among
      older patients who might also derive less benefit from oxaliplatin. We evaluated
      the association between adjuvant oxaliplatin-based chemotherapy and neurotoxicity
      outcomes in an elderly cohort of patients. PATIENTS AND METHODS: A population
      based cohort of patients aged > 65 years with stage II and III colorectal cancer
      treated with adjuvant therapy in Ontario, Canada was identified using the Ontario
      Cancer Registry. Cause-specific hazard models were used to estimate the effect of
      oxaliplatin exposure on the cause-specific hazard ratio (CHR) of peripheral
      neuropathy after accounting for the competing risk of death. RESULTS: We
      identified 3607 patients aged > 65 years with stage II and III colorectal cancer.
      Of these patients, 1541 (43%) had been treated with an oxaliplatin-based regimen.
      Compared with subjects receiving non-oxaliplatin-based regimens, patients aged >=
      70 years at the time of cancer diagnosis who are subsequently treated with
      oxaliplatin were more likely to develop peripheral neuropathy (CHR, 2.3; 95%
      confidence interval [CI], 1.53-3.35; P < .0001). This association was not
      significant in patients aged 66 to 69 years (CHR, 0.93; 95% CI, 0.50-1.72; P =
      .812). Formal interaction testing confirmed that the effect of oxaliplatin on
      neuropathy was more pronounced in patients aged >= 70 years compared with
      patients aged 66 to 69 years (P = .03). CONCLUSION: Colorectal cancer patients
      aged >= 70 years at the time of cancer diagnosis who are subsequently treated
      with oxaliplatin have a significant risk of developing peripheral neuropathy.
      This should be considered in clinical decision making, especially because of the
      limited data supporting an oxaliplatin benefit in this age group.

PMID- 28434886
TI  - Reply by Authors.

PMID- 28434885
TI  - Early Performance on an Eye Surgery Simulator Predicts Subsequent Resident
      Surgical Performance.
AB  - OBJECTIVE: To examine early performance on an eye surgery simulator and its
      relationship to subsequent live surgical performance in a single large residency
      program. DESIGN: Retrospective study. SETTING: Massachusetts Eye and Ear, Harvard
      Medical School, Department of Ophthalmology. METHODS: In a retrospective study,
      we compared performance of 30 first-year ophthalmology residents on an eye
      surgery simulator to their surgical skills as third-year residents. Variables
      collected from the eye surgery simulator included scores on the following modules
      of the simulator (Eyesi, VRmagic, Mannheim, Germany): antitremor training level
      1, bimanual training level 1, capsulorhexis level 1 (configured), forceps
      training level 1, and navigation training level 1. Subsequent surgical
      performance was assessed using the total number of phacoemulsification cataract
      surgery cases for each resident, as well as the number performed as surgeon
      during residency and scores on global rating assessment of skills in intraocular
      surgery (GRASIS) scales during the third year of residency. Spearman correlation
      coefficients were calculated between each of the simulator performance and
      subsequent surgical performance variables. We also compared variables in a small
      group of residents who needed extra help in learning cataract surgery to the
      other residents in the study. MAIN OUTCOME MEASURES: Relationships between Eyesi
      scores early in residency and surgical performance measures in the final year of
      residency. RESULTS: A total of 30 residents had Eyesi data from their first year
      of residency and had already graduated so that all subsequent surgical
      performance data were available. There was a significant correlation between
      capsulorhexis task score on the simulator and total surgeries (r = 0.745, p =
      0.008). There was a significant correlation between antitremor training level 1
      (r = 0.554, p = 0.040), and forceps training level 1 (r = 0.622, p = 0.023) with
      primary surgery numbers. There was a significant correlation between forceps
      training level 1 (r = 0.811, p = 0.002), and navigation training level 1 (r =
      0.692, p = 0.013) with total GRASIS score. There was a significant inverse
      correlation between total GRASIS score and residents in need of extra help (r = 
      0.358, p = 0.003). CONCLUSION: Module scores on an eye surgery simulator early in
      residency may predict a resident's future performance in the operating room.
      These scores may allow early identification of residents in need of supplemental
      training in cataract surgery.

PMID- 28434887
TI  - Editorial Comment.

PMID- 28434889
TI  - Depletion of TM6SF2 disturbs membrane lipid composition and dynamics in HuH7
      hepatoma cells.
AB  - A polymorphism of TM6SF2 associates with hepatic lipid accumulation and reduction
      of triacylglycerol (TAG) secretion, but the function of the encoded protein has
      remained enigmatic. We studied the effect of stable TM6SF2 knock-down on the
      lipid content and composition, mitochondrial fatty acid oxidation and organelle
      structure of HuH7 hepatoma cells. Knock-down of TM6SF2 resulted in intracellular
      accumulation of TAGs, cholesterol esters, phosphatidylcholine (PC) and
      phosphatidylethanolamine. In all of these lipid classes, polyunsaturated lipid
      species were significantly reduced while saturated and monounsaturated species
      increased their proportions. The PCs encountered relative and absolute
      arachidonic acid (AA, 20:4n-6) depletion, and AA was also reduced in the total
      cellular fatty acid pool. Synthesis and turnover of the hepatocellular
      glycerolipids was enhanced. The TM6SF2 knock-down cells secreted lipoprotein-like
      particles with a smaller diameter than in the controls, and more
      lysosome/endosome structures appeared in the knock-down cells. The mitochondrial
      capacity for palmitate oxidation was significantly reduced. These observations
      provide novel clues to TM6SF2 function and raise altered mebrane lipid
      composition and dynamics among the mechanism(s) by which the protein deficiency
      disturbs hepatic TAG secretion.

PMID- 28434888
TI  - Melorheostosis: Exome sequencing of an associated dermatosis implicates
      postzygotic mosaicism of mutated KRAS.
AB  - Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic
      or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal
      pattern. The prevailing hypothesis for MEL invokes postzygotic mosaicism.
      Sometimes scleroderma-like skin changes, considered a representation of the
      pathogenetic process of MEL, overlie the bony changes, and sometimes MEL becomes
      malignant. Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia
      that features symmetrically distributed punctate osteosclerosis due to
      heterozygous loss-of-function mutation within LEMD3. Rarely, radiographic
      findings of MEL occur in OPK. However, germline mutation of LEMD3 does not
      explain sporadic MEL. To explore if mosaicism underlies MEL, we studied a boy
      with polyostotic MEL and characteristic overlying scleroderma-like skin, a few
      bony lesions consistent with OPK, and a large epidermal nevus known to usually
      harbor a HRAS, FGFR3, or PIK3CA gene mutation. Exome sequencing was performed to
      ~100* average read depth for his two dermatoses, two areas of normal skin, and
      peripheral blood leukocytes. As expected for non-malignant tissues, the patient's
      mutation burden in his normal skin and leukocytes was low. He, his mother, and
      his maternal grandfather carried a heterozygous, germline, in-frame, 24-base-pair
      deletion in LEMD3. Radiographs of the patient and his mother revealed bony foci
      consistent with OPK, but she showed no MEL. For the patient, somatic variant
      analysis, using four algorithms to compare all 20 possible pairwise combinations
      of his five DNA samples, identified only one high-confidence mutation,
      heterozygous KRAS Q61H (NM_033360.3:c.183A>C, NP_203524.1:p.Gln61His), in both
      his dermatoses but absent in his normal skin and blood. Thus, sparing our patient
      biopsy of his MEL bone, we identified a heterozygous somatic KRAS mutation in his
      scleroderma-like dermatosis considered a surrogate for MEL. This implicates
      postzygotic mosaicism of mutated KRAS, perhaps facilitated by germline LEMD3
      haploinsufficiency, causing his MEL.

PMID- 28434891
TI  - Nanotechnology based therapeutic modality to boost anti-tumor immunity and
      collapse tumor defense.
AB  - Cancer is still the leading cause of death. While traditional treatments such as
      surgery, chemotherapy and radiotherapy play dominating roles, recent
      breakthroughs in cancer immunotherapy indicate that the influence of immune
      system on cancer development is virtually beyond our expectation. Manipulating
      the immune system to fight against cancer has been thriving in recent years.
      Further understanding of tumor anatomy provides opportunities to put a brake on
      immunosuppression by overcoming tumor intrinsic resistance or modulating tumor
      microenvironment. Nanotechnology which provides versatile engineered approaches
      to enhance therapeutic effects may potentially contribute to the development of
      future cancer treatment modality. In this review, we will focus on the
      application of nanotechnology both in boosting anti-tumor immunity and collapsing
      tumor defense.

PMID- 28434890
TI  - Brain lipidomic changes after morphine, cocaine and amphetamine administration -
      DESI - MS imaging study.
AB  - Drug addiction is a complex disorder, evoking significant changes in the proteome
      of the central nervous system. To check if there are also changes in the
      lipidomic profiles we used desorption electrospray-MS technique for imaging of
      the brain slices of rats exposed to morphine, cocaine and amphetamine. Our
      investigations showed alternative regulation of selected lipid's levels in the
      central nervous system structures, under the influence of applied drugs. Results
      of our investigations can show changes in the brain treated with drugs of abuse
      in the new light, indicating role of the lipids in the addiction development.

PMID- 28434892
TI  - Effective humoral immune response from a H1N1 DNA vaccine delivered to the skin
      by microneedles coated with PLGA-based cationic nanoparticles.
AB  - Intradermal DNA vaccination is a promising method of immunization that overcomes
      some practical drawbacks of conventional intramuscular vaccinations. However, it
      is difficult to deliver DNA vaccines to target cells in the skin and polyplexes.
      This study outlines the development of an intradermal pH1N1 DNA vaccine delivery
      platform using microneedles (MNs) coated with a polyplex containing poly lactic
      co-glycolic acid/polyethyleneimine (PLGA/PEI) nanoparticles (NPs). Stainless
      steel MNs with enhanced hydrophilicity have been manufactured by silanization,
      which improves coating efficiency. MNs coated with the polyplex encapsulating
      pDNA vaccine were prepared by optimizing the N/P ratio, with a 6:1 ratio showing
      the highest transfection efficiency in mammalian cells. Polyplexes were coated on
      MNs without severe aggregation of the polyplex in the dry form. The coated
      polyplex rapidly dissolved in porcine skin (within 5min) and induced a greater
      humoral immune response than that of intramuscular polyplex delivery or naked
      pH1N1 DNA vaccine delivery by a dry-coated MN. These results indicate that
      intradermal delivery of pDNA vaccines within a cationic polyplex coated on MNs
      has potential in skin immunizations.

PMID- 28434893
TI  - What makes people leave their food? The interaction of personal and situational
      factors leading to plate leftovers in canteens.
AB  - In order to provide a basis for the reduction of food losses, our study analyzes
      individual food choice, eating and leftover behavior in a university canteen by
      consideration of personal, social and environmental determinants. Based on an
      extended literature review, a structural equation model is derived and
      empirically tested for a sample of 343 students. The empirical estimates support
      the derived model with a good overall model fit and sufficient R2 values for
      dependent variables. Hence, our results provide evidence for a general
      significant impact of behavioral intention and related personal and social
      determinants as well as for the relevance of environmental/situational
      determinants such as portion sizes and palatability of food for plate leftovers.
      Moreover, we find that environmental and personal determinants are interrelated
      and that the impact of different determinants is relative to perceived time
      constraints during a visit of the university canteen. Accordingly, we conclude
      that simple measures to decrease avoidable food waste may take effects via
      complex and interrelated behavioral structures and that future research should
      focus on these effects to understand and change food leftover behavior.

PMID- 28434895
TI  - The use of endoprotheses for patients with complex asymmetry: A clinical case
      study.
AB  - Facial asymmetry requires multidisciplinary management. In some cases,
      predictable problems due to congenital abnormalities can be corrected by early
      orthodontic treatment. Orthodontics is nevertheless often part of an
      orthosurgical treatment plan. The solutions are conventional and familiar:
      maxillomandibular rotation osteotomy and genioplasty. Many cases can be treated
      in this way, but there is often persistent residual asymmetry due to loss of
      volume that is not corrected by these techniques. The use of maxillo-acial
      endoprostheses designed on the basis of three-dimensional craniofacial analyses
      can rebalance volumes simply and with due regard to the patient's anatomy. This
      multistage management will be illustrated here through a complex clinical case.

PMID- 28434894
TI  - [A real-world study focused on the effectiveness and safety of adalimumab as
      first-line anti-TNF treatment for pediatric Crohn's disease].
AB  - BACKGROUND AND OBJECTIVES: Adalimumab (ADA), a monoclonal humanised anti-TNF
      antibody, is usually prescribed as a second-line treatment in paediatric Crohn's
      disease (CD) patients who have become unresponsive or developed intolerance to
      infliximab (IFX). In the case series reported, more than 70% of patients had
      initially been treated with IFX. Data on short- and long-term effectiveness of
      ADA in anti-TNF naive patients is limited. The aim of this study is to describe
      our experience with ADA as a first-line anti-TNF in paediatric CD patients.
      MATERIAL AND METHODS: This is a multicentre retrospective study including anti
      TNF naive paediatric CD patients treated with ADA as first-line anti-TNF.
      RESULTS: Sixty-two patients (34males), with a mean age of 13.0+/-2.4years and a
      disease duration of 7.3 (IQR 2.7-21) months were included. Median wPCDAI was 35
      (IQR 24.3-47.5). Fifty-eight out of 62 (93.5%) were on combo therapy at baseline.
      Clinical remission at week12 was achieved in 50 out of 62 (80.6%) and in 57 out
      of 60 (95.0%) at week52. Eight patients (13%) reported adverse events. Mean
      height, growth rate and BMI z-scores improved significantly between baseline and
      week 52, especially in patients with growth failure. CONCLUSIONS: ADA treatment
      leads to lasting clinical remission in anti-TNF naive paediatric patients with
      CD. ADA significantly improved growth rate in children with CD who had growth
      delay at baseline.

PMID- 28434896
TI  - ?

PMID- 28434897
TI  - Epidemiology of polyomavirus BK (BKV) and the emergent African variant in kidney
      and bone marrow transplant recipients in the Fundacion Valle del Lili in Cali,
      Colombia.
AB  - To describe the epidemiology of BKV and to assess the presence of the African
      variant in bone marrow and kidney transplant patients who have suspected BKV
      reactivation. A descriptive study was conducted, using institutional records, at
      the Fundacion Valle del Lili, Cali-Colombia. The overall prevalence of BKV during
      the study period was 51%. The African variant was identified in 49.4% of samples
      that were positive for BKV. 50.6% of the samples were found to have the wild
      strain of BKV. Among BKV positive patients, 57% were kidney transplant recipients
      and 43% were bone marrow transplant recipients. This is the first epidemiological
      study describing the African variant of BKV in Colombia.

PMID- 28434898
TI  - Bacteraemia due to AmpC beta-lactamase-producing Escherichia coli in hospitalized
      cancer patients: risk factors, antibiotic therapy, and outcomes.
AB  - AmpC beta-lactamase-producing Escherichia coli (AmpC-EC) is one of the main
      antimicrobial resistant pathogens in patients with cancer. A cohort study was
      performed to evaluate the risk factors, antibiotic therapy, and outcomes of AmpC
      EC bacteraemia in hospitalized cancer patients from September 2012 through
      December 2015. Two hundred forty-eight cases of E. coli bacteraemia were
      documented in cancer patients, 51 (20.6%) were caused by AmpC-EC and 197 (79.4%)
      were caused with non-AmpC-EC. Prior exposure to cephalosporins (OR 2.786; 95% CI:
      1.094-7.091; P=0.032), carbapenems (OR 2.296; 95% CI: 1.054-5.004; P=0.036), and
      invasive procedures (OR 4.237; 95% CI: 1.731-10.37; P=0.002) were identified as
      independent risk factors for AmpC-EC. The time to positivity (TTP) of patients
      with AmpC-EC bacteraemia tended to be significantly shorter than that of non-AmpC
      EC (8.33+/-2.18h versus 9.48+/-3.82h; P=0.006), and had a higher 30-day mortality
      rate in AmpC-EC compared with non-AmpC-EC (25.5% versus 12.2%; P=0.018).
      Metastasis (OR=2.778, 95% CI: 1.078-7.162; P=0.034), the presence of septic shock
      (OR=4.983, 95% CI: 1.761-14.10; P=0.002), and organ failure (OR=24.51 95% CI:
      9.884-60.81; P<0.001) were independently associated with the overall mortality.
      The mortality rate showed a gradual increase when appropriate antibiotic therapy
      (AAT) was delayed more than 48h as determined by the trend test (P<0.001). In
      conclusion, this study showed that prevalence of AmpC-EC was high in hospitalized
      cancer patients of our area. Thus, it is necessary to apply appropriate
      therapeutic approaches and improve outcomes based on the analysis of risk factors
      for the acquisition of AmpC-EC.

PMID- 28434899
TI  - Mechanisms responsible for imipenem resistance among Pseudomonas aeruginosa
      clinical isolates exposed to imipenem concentrations within the mutant selection
      window.
AB  - The aim of this study was to determine the propensities of imipenem to select for
      resistant Pseudomonas aeruginosa mutants by determining the mutant prevention
      concentrations (MPCs) for 9 unrelated clinical isolates and the accession of any
      relationship with mechanisms of resistance development. The MPC/MIC ratios ranged
      from 4 to 16. Detection of resistance mechanisms in the mutant derivatives of the
      nine isolates mainly revealed inactivating mutations in the gene coding for outer
      membrane protein OprD. Point mutations leading to premature stop codons or amino
      acid substitution S278P, >=1bp deletion leading to frameshift mutations and
      interruption of the oprD by an insertion sequence, were observed. MPC and mutant
      selection window (MSW) are unique parameters that may guide the implementation of
      antimicrobial treatment, providing useful information about the necessary
      imipenem concentration needed in the infection area, in order to avoid the
      emergence of resistance, especially in clinical situations with high bacterial
      load.

PMID- 28434900
TI  - Breast Cancer in a Pectoralis Major Myocutaneous Flap Used for the Reconstruction
      of Tongue Cancer: A Case Report.
AB  - Breast cancers are the most common cancers in women. However, breast cancer
      occurring in a pectoralis major myocutaneous flap is extremely rare. This article
      describes a case of breast cancer occurring in such a flap used for
      reconstruction of the tongue in a 72-year-old woman. Follow-up computed tomogram
      depicted a slowly growing mass in the flap. Thirty-nine months postoperatively, a
      fine-needle aspiration biopsy specimen taken from the lesion suggested glandular
      carcinoma. The patient was diagnosed with breast cancer in the neck area of the
      flap and tumor excision was performed. Histologic examination of the excised
      tumor showed tumor cells arranged in cords, with tubular and cribriform
      carcinomas near the pectoral muscle with adipose tissue. The cytoplasm was
      abundant and eosinophilic. Thus, the patient was diagnosed with invasive ductal
      carcinoma in the pectoralis major flap. Sequential radiotherapy was performed to
      the neck with a total radiation dose of 50 Gy. Furthermore, the patient received
      oral anastrozole 1 mg daily as systemic adjuvant therapy for the receptor
      positive breast malignancy. One year after surgery, the patient was alive with no
      evidence of disease. Including this case, only 2 cases of breast cancer in a
      pectoralis major myocutaneous flap used for reconstruction in the head and neck
      region have been reported.

PMID- 28434901
TI  - Male song sparrows have elevated testosterone in response to neighbors versus
      strangers.
AB  - Upon hearing a conspecific signal, animals must assess their relationship with
      the signaller and respond appropriately. Territorial animals usually respond more
      aggressively to strangers than neighbors in a phenomenon known as the "dear enemy
      effect". This phenomenon likely evolved because strangers represent a threat to
      an animal's territory tenure and parentage, whereas neighbors only represent a
      threat to an animal's parentage because they already possess a territory
      (providing territory boundaries are established and stable). Although the dear
      enemy effect has been widely documented using behavioral response variables,
      little research has been conducted on the physiological responses of animals to
      neighbors versus strangers. We sought to investigate whether the dear enemy
      effect is observed physiologically by exposing territorial male song sparrows
      (Melospiza melodia) to playback simulating a neighbor or a stranger, and then
      collecting blood samples to measure plasma testosterone levels. We predicted that
      song sparrows would exhibit increased testosterone levels after exposure to
      stranger playback compared to neighbor playback, due to the role testosterone
      plays in regulating aggression. Contrary to our prediction, we found that song
      sparrows had higher testosterone levels after exposure to neighbor playback
      compared to stranger playback. We discuss several explanations for our result,
      notably that corticosterone may regulate the dear enemy effect in male song
      sparrows and this may inhibit plasma testosterone. Future studies will benefit
      from examining corticosterone in addition to testosterone, to better understand
      the hormonal underpinnings of the dear enemy effect.

PMID- 28434902
TI  - Intravital microscopy of biosensor activities and intrinsic metabolic states.
AB  - Intravital microscopy (IVM) is an imaging tool that is capable of detecting
      subcellular signaling or metabolic events as they occur in tissues in the living
      animal. Imaging in highly scattering biological tissues, however, is challenging
      because of the attenuation of signal in images acquired at increasing depths.
      Depth-dependent signal attenuation is the major impediment to IVM, limiting the
      depth from which significant data can be obtained. Therefore, making quantitative
      measurements by IVM requires methods that use internal calibration, or
      alternatively, a completely different way of evaluating the signals. Here, we
      describe how ratiometric imaging of genetically encoded biosensor probes can be
      used to make quantitative measurements of changes in the activity of cell
      signaling pathways. Then, we describe how fluorescence lifetime imaging can be
      used for label-free measurements of the metabolic states of cells within the
      living animal.

PMID- 28434903
TI  - Measuring transcription dynamics in living cells using a photobleaching approach.
AB  - The transcriptional kinetics of RNA polymerase II, the enzyme responsible for
      mRNA transcription in the nucleoplasm, can be modulated by a variety of factors.
      It is therefore important to establish experimental systems that will enable the
      readout of transcription kinetics of specific genes as they occur in real time
      within individual cells. This can be performed by implementing fluorescent
      tagging of the mRNA under live-cell conditions. This chapter describes how to
      generate fluorescently tagged genes and mRNA, and how a photobleaching approach
      can produce information on mRNA transcription kinetics.

PMID- 28434904
TI  - Deep sequencing approaches for the analysis of prokaryotic transcriptional
      boundaries and dynamics.
AB  - The identification of the protein-coding regions of a genome is straightforward
      due to the universality of start and stop codons. However, the boundaries of the
      transcribed regions, conditional operon structures, non-coding RNAs and the
      dynamics of transcription, such as pausing of elongation, are non-trivial to
      identify, even in the comparatively simple genomes of prokaryotes. Traditional
      methods for the study of these areas, such as tiling arrays, are noisy, labour
      intensive and lack the resolution required for densely-packed bacterial genomes.
      Recently, deep sequencing has become increasingly popular for the study of the
      transcriptome due to its lower costs, higher accuracy and single nucleotide
      resolution. These methods have revolutionised our understanding of prokaryotic
      transcriptional dynamics. Here, we review the deep sequencing and data analysis
      techniques that are available for the study of transcription in prokaryotes, and
      discuss the bioinformatic considerations of these analyses.

PMID- 28434905
TI  - Using quantitative intravital multiphoton microscopy to dissect hepatic transport
      in rats.
AB  - Hepatic solute transport is a complex process whose disruption is associated with
      liver disease and drug-induced liver injury. Intravital multiphoton fluorescence
      excitation microscopy provides the spatial and temporal resolution necessary to
      characterize hepatic transport at the level of individual hepatocytes in vivo and
      thus to identify the mechanisms and cellular consequences of cholestasis. Here we
      present an overview of the use of fluorescence microscopy for studies of hepatic
      transport in living animals, and describe how we have combined methods of
      intravital microscopy and digital image analysis to dissect the effects of drugs
      and pathological conditions on the function of hepatic transporters in vivo.

PMID- 28434906
TI  - The evolution of parasitic and mutualistic plant-virus symbioses through
      transmission-virulence trade-offs.
AB  - Virus-plant interactions range from parasitism to mutualism. Viruses have been
      shown to increase fecundity of infected plants in comparison with uninfected
      plants under certain environmental conditions. Increased fecundity of infected
      plants may benefit both the plant and the virus as seed transmission is one of
      the main virus transmission pathways, in addition to vector transmission. Trade
      offs between vertical (seed) and horizontal (vector) transmission pathways may
      involve virulence, defined here as decreased fecundity in infected plants. To
      better understand plant-virus symbiosis evolution, we explore the ecological and
      evolutionary interplay of virus transmission modes when infection can lead to an
      increase in plant fecundity. We consider two possible trade-offs: vertical seed
      transmission vs infected plant fecundity, and horizontal vector transmission vs
      infected plant fecundity (virulence). Through mathematical models and numerical
      simulations, we show (1) that a trade-off between virulence and vertical
      transmission can lead to virus extinction during the course of evolution, (2)
      that evolutionary branching can occur with subsequent coexistence of mutualistic
      and parasitic virus strains, and (3) that mutualism can out-compete parasitism in
      the long-run. In passing, we show that ecological bi-stability is possible in a
      very simple discrete-time epidemic model. Possible extensions of this study
      include the evolution of conditional (environment-dependent) mutualism in plant
      viruses.

PMID- 28434907
TI  - Historical Perspectives on the Use of Technology in Maternal and Infant Care.

PMID- 28434908
TI  - Duchenne muscular dystrophy in a female with compound heterozygous contiguous
      exon deletions.
AB  - Females with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy
      (BMD) mutations rarely exhibit clinical symptoms from childhood, although
      potential mechanisms for symptoms associated with DMD and BMD in females have
      been reported. We report the case of a female DMD patient with a clinical course
      indistinguishable from that of a male DMD patient, and who possessed compound
      heterozygous contiguous exon deletions in the dystrophin gene. She exhibited
      Gowers' sign, calf muscle hypertrophy, and a high serum creatine kinase level at
      2 years. Her muscle pathology showed most of the fibers were negative for
      dystrophin immunohistochemical staining. She lost ambulation at 11 years.
      Multiplex ligation-dependent probe amplification analysis of this gene detected
      one copy of exons 48-53; she was found to be a BMD carrier with an in-frame
      deletion. Messenger RNA from her muscle demonstrated out-of-frame deletions of
      exons 48-50 and 51-53 occurring on separate alleles. Genomic DNA from her
      lymphocytes demonstrated the accurate deletion region on each allele. To our
      knowledge, this is the first report on a female patient possessing compound
      heterozygous contiguous exon deletions in the dystrophin gene, leading to DMD.

PMID- 28434910
TI  - The composition and biomechanical properties of human cryopreserved aortas,
      pulmonary trunks, and aortic and pulmonary cusps.
AB  - Human cryopreserved allografts of pulmonary and aortic heart valves, aortas and
      pulmonary trunks are used for valve replacement. However, it is unknown how the
      composition of these allografts relate to their mechanical properties. Our aims
      were to correlate the histological compositions and passive mechanical properties
      of aortic and pulmonary valves and to observe the microcracks of aortas and
      pulmonary trunks. The following parameters were quantified: ultimate stress;
      ultimate strain; Young's modulus of elasticity; valve cusp wall thickness;
      pulmonary and aortic intima-media thickness; area fraction of elastin, collagen
      and calcification; and length density of elastic fibres. The propagation of
      experimentally induced microcracks avoided elastic fibres. Ultimate strain was
      negatively correlated with the area fraction of calcification (r=-0.4) in aortas.
      Ultimate stress (r=0.27) and Young's modulus in small deformation (r=0.29) and in
      large deformation (r=0.32) correlated with wall thickness in valve cusps. Young's
      modulus (r=0.34) and ultimate strain (r=0.31) correlated with intima-media
      thickness. Ultimate strain correlated with the area fraction of elastin (r=-0.40)
      and collagen in the arteries (r=0.31). As conventional histology does not fully
      explain the mechanical properties of cryopreserved grafts, both morphological and
      biomechanical tests should be used complementarily when characterizing the ageing
      of the grafts.

PMID- 28434909
TI  - Facilitating orphan drug development: Proceedings of the TREAT-NMD International
      Conference, December 2015, Washington, DC, USA.

PMID- 28434911
TI  - Does quantity ensure quality? Standardized OSCE-stations for outcome-oriented
      evaluation of practical skills at different medical faculties.
AB  - BACKGROUND: Practical skills are often assessed using Objective Structured
      Clinical Skill Exams (OSCE). Nevertheless, in Germany, interchange and agreement
      between different medical faculties or a general agreement on the minimum
      standard for passing is lacking. METHODS: We developed standardized OSCE-stations
      for assessing structured clinical examination of knee and shoulder joint with
      identical checklists and evaluation standards. These were implemented into the
      OSCE-course at five different medical faculties. Learning objectives for passing
      the stations were agreed beforehand. At each faculty, one reference examiner
      scored independently of the local examiner. Outcome of the students at the
      standardized station was compared between faculties and correlated to their total
      outcome at the OSCE, to their results at the Part One of the National Medical
      Licensing Examination as a reference test during medical studies and to their
      previous amount of lessons in examining joints. RESULTS: Comparing the results of
      the reference examiner, outcome at the station differed significantly between
      some of the participating medical faculties. Depending on the faculty, mean total
      results at the knee-examination-station differed from 64.4% to 77.9% and at the
      shoulder-examination-station from 62.6% to 79.2%. Differences were seen in
      knowledge-based items and also in competencies like communication and
      professional manner. There was a weak correlation between outcome at the joint
      examination-OSCE-station and Part One of the National Medical Licensing
      Examination, and a modest correlation between outcome at the joint-examination
      station and total OSCE-result. Correlation to the previous amount of lessons in
      examining joint was also weak. CONCLUSION: Although addressing approved learning
      objectives, different outcomes were achieved when testing a clinical skill at
      different medical faculties with a standardized OSCE-station. Results can be used
      as a tool for evaluating lessons, training and curricula at the different sites.
      Nevertheless, this study shows the importance of information exchange and
      agreement upon certain benchmarks and evaluation standards when assessing
      practical skills.

PMID- 28434912
TI  - The Role of Social-Emotional and Social Network Factors in the Relationship
      Between Academic Achievement and Risky Behaviors.
AB  - BACKGROUND: We examined whether standardized test scores and grades are related
      to risky behaviors among low-income minority adolescents and whether social
      networks and social-emotional factors explained those relationships. METHODS: We
      analyzed data from 929 high school students exposed by natural experiment to high
      or low-performing academic environments in Los Angeles. We collected information
      on grade point average (GPA), substance use, sexual behaviors, participation in
      fights, and carrying a weapon from face-to-face interviews and obtained
      California math and English standardized test results. Logistic regression and
      mediation analyses were used to examine the relationship between achievement and
      risky behaviors. RESULTS: Better GPA and California standardized test scores were
      strongly associated with lower rates of substance use, high-risk sexual
      behaviors, and fighting. The unadjusted relative odds of monthly binge drinking
      was 0.72 (95% confidence interval, 0.56-0.93) for 1 SD increase in standardized
      test scores and 0.46 (95% confidence interval, 0.29-0.74) for GPA of B- or higher
      compared with C+ or lower. Most associations disappeared after controlling for
      social-emotional and social network factors. Averaged across the risky behaviors,
      mediation analysis revealed social-emotional factors accounted for 33% of the
      relationship between test scores and risky behaviors and 43% of the relationship
      between GPA with risky behaviors. Social network characteristics accounted for
      31% and 38% of the relationship between behaviors with test scores and GPA,
      respectively. Demographic factors, parenting, and school characteristics were
      less important explanatory factors. CONCLUSIONS: Social-emotional factors and
      social network characteristics were the strongest explanatory factors of the
      achievement-risky behavior relationship and might be important to understanding
      the relationship between academic achievement and risky behaviors.

PMID- 28434913
TI  - Development of School-Based Asthma Management Programs in Rochester, New York:
      Presented in Honor of Dr Robert Haggerty.
AB  - In the spirit of Dr. Haggerty's teachings, we present an overview of our work to
      improve care for children with asthma in the context of 3 lessons learned: 1) the
      importance of providing integrated services across disciplinary boundaries for
      children with chronic illness, 2) the need to move from a care model focused only
      on the individual child to a model focused on the child, family, and community,
      and 3) the need to expand beyond the local community and take a broad perspective
      on improving health on a national level. The goal of our program is to develop
      sustainable models to overcome the multiple obstacles to effective preventive
      care for urban children with asthma. The primary intervention for our original
      School-Based Asthma Therapy program was directly observed administration of
      preventive asthma medications in school (with dose adjustments on the basis of
      National Heart, Lung, and Blood Institute guidelines). We found that children who
      received preventive medications in school through directly observed therapy had
      improved outcomes across multiple outcome measures. Our subsequent asthma
      programs have focused on dissemination and sustainability, with the incorporation
      of communication technology to enhance the system of care. We are currently
      testing the 'School-Based Telemedicine Enhanced Asthma Management' program,
      including 400 children with persistent asthma from the Rochester City School
      District. This program includes directly observed administration of preventive
      asthma medication at school, and school-based telemedicine to assure appropriate
      evaluation, preventive medication prescription, and follow-up care. It is
      designed to implement and sustain guideline-based asthma care through existing
      community infrastructure, and could serve as a model for the integration of
      services in rural as well as urban communities.

PMID- 28434914
TI  - Full-length, Oligomeric Structure of Wzz Determined by Cryoelectron Microscopy
      Reveals Insights into Membrane-Bound States.
AB  - Wzz is an integral inner membrane protein involved in regulating the length of
      lipopolysaccharide O-antigen glycans and essential for the virulence of many Gram
      negative pathogens. In all Wzz homologs, the large periplasmic domain is proposed
      to be anchored by two transmembrane helices, but no information is available for
      the transmembrane and cytosolic domains. Here we have studied purified oligomeric
      Wzz complexes using cryoelectron microscopy and resolved the transmembrane
      regions within a semi-continuous detergent micelle. The transmembrane helices of
      each monomer display a right-handed super-helical twist, and do not interact with
      the neighboring transmembrane domains. Modeling, flexible fitting and multiscale
      simulation approaches were used to study the full-length complex and to provide
      explanations for the influence of the lipid bilayer on its oligomeric status.
      Based on structural and in silico observations, we propose a new mechanism for O
      antigen chain-length regulation that invokes synergy of Wzz and its polymerase
      partner, Wzy.

PMID- 28434915
TI  - X-Ray Crystallography and Electron Microscopy of Cross- and Multi-Module
      Nonribosomal Peptide Synthetase Proteins Reveal a Flexible Architecture.
AB  - Nonribosomal peptide synthetases (NRPS) are macromolecular machines that produce
      peptides with diverse activities. Structural information exists for domains,
      didomains, and even modules, but little is known about higher-order organization.
      We performed a multi-technique study on constructs from the dimodular NRPS DhbF.
      We determined a crystal structure of a cross-module construct including the
      adenylation (A) and peptidyl carrier protein (PCP) domains from module 1 and the
      condensation domain from module 2, complexed with an adenosine-vinylsulfonamide
      inhibitor and an MbtH-like protein (MLP). The action of the inhibitor and the
      role of the MLP were investigated using adenylation reactions and isothermal
      titration calorimetry. In the structure, the PCP and A domains adopt a novel
      conformation, and noncovalent, cross-module interactions are limited. We
      calculated envelopes of dimodular DhbF using negative-stain electron microscopy.
      The data show large conformational variability between modules. Together, our
      results suggest that NRPSs lack a uniform, rigid supermodular architecture.

PMID- 28434917
TI  - Conformational Dynamics and Allostery in E2:E3 Interactions Drive Ubiquitination:
      gp78 and Ube2g2.
AB  - Conformational dynamics plays a fundamental role in molecular recognition and
      activity in enzymes. The ubiquitin-conjugating enzyme (E2) Ube2g2 functions with
      the ubiquitin ligase (E3) gp78 to assemble poly-ubiquitin chains on target
      substrates. Two domains in gp78, RING and G2BR, bind to two distant regions of
      Ube2g2, and activate it for ubiquitin (Ub) transfer. G2BR increases the affinity
      between the RING and Ube2g2 by 50-fold, while the RING catalyzes the transfer of
      Ub from the Ube2g2~Ub conjugate. How G2BR and RING activate Ube2g2 is unclear. In
      this work, conformational dynamics in Ube2g2 revealed a clear correlation of
      binding G2BR and RING with the sequential progression toward Ub transfer. The
      interrelationship of the existence and exchange between ground and excited states
      leads to a dynamic energy landscape model, in which redistribution of populations
      contributes to allostery and activation. These findings provide insight into
      gp78's modulation of conformational exchange in Ube2g2 to stimulate
      ubiquitination.

PMID- 28434918
TI  - Forming and activating an internal facilitation group for successful
      implementation: A qualitative study.
AB  - BACKGROUND: This study focuses on an implementation facilitation strategy to
      improve the delivery of anticoagulation care within pharmacy-run clinics across 8
      Veterans Health Administration (VA) medical centers. Other studies have explored
      various models of implementation facilitation, including external facilitation
      (EF), internal facilitation (IF), and blended facilitation (BF) combining both
      approaches. This study focuses on the use of an internal facilitation team of
      anticoagulation coordinators representing 8 VA anticoagulation clinics to enhance
      the implementation process. This study examines how the team became instrumental
      in the successful implementation of evidence-based practice change. METHODS: Semi
      structured interviews were conducted annually over 4 years with representatives
      from each site, the internal facilitators (site champions), at 8 VA hospitals (47
      interviews). Additionally, five external facilitators, experts in quality
      improvement and anticoagulation care who guided the implementation, were
      interviewed. Analysis drew on a deductive approach based on the Promoting Action
      on Research Implementation in Health Services (PARIHS) model and emergent
      thematic analysis to identify factors related to effectiveness of the internal
      facilitation team. RESULTS: Key findings are that the following factors enhanced
      successful uptake of the anticoagulation initiative: 1) Regular participation by
      the site champion in the internal facilitation team; 2) Champion strongly
      committed to being an agent of change; and 3) Champion received greater support
      from their supervisors. The first and second factors are interrelated, as
      internal facilitators who actively and regularly participated in the internal
      facilitation team often became truly committed to the improvement project. Both
      factors relate to the third, as supervisor support not only facilitated changes
      in practice, but also facilitated regular team attendance and stronger
      participation. CONCLUSIONS: Our study adds to implementation science by detailing
      how internal facilitators learn their skills over time, and how a group of
      internal facilitators can help each other succeed. These findings can guide those
      who wish to incorporate internal facilitation teams as an implementation
      strategy, and demonstrate how sites can build capacity for implementation
      efforts. SYNOPSIS: This study focuses on an implementation facilitation strategy
      to improve the delivery of anticoagulation care within pharmacy-run clinics
      across 8 Veterans Health Administration medical centers. Internal facilitators
      (IFs) guided by and supported by an external facilitators (EF), successfully
      implemented the clinical innovation. This study examines how the IF group became
      instrumental in the successful implementation of evidence-based practice change.

PMID- 28434916
TI  - The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to
      Specific Viral Glycans.
AB  - Select lectins have powerful anti-viral properties that effectively neutralize
      HIV-1 by targeting the dense glycan shield on the virus. Here, we reveal the
      mechanism by which one of the most potent lectins, BanLec, achieves its
      inhibition. We identify that BanLec recognizes a subset of high-mannose glycans
      via bidentate interactions spanning the two binding sites present on each BanLec
      monomer that were previously considered separate carbohydrate recognition
      domains. We show that both sites are required for high-affinity glycan binding
      and virus neutralization. Unexpectedly we find that BanLec adopts a tetrameric
      stoichiometry in solution whereby the glycan-binding sites are positioned to
      optimally target glycosylated viral spikes. The tetrameric architecture, together
      with bidentate binding to individual glycans, leads to layers of multivalency
      that drive viral neutralization through enhanced avidity effects. These
      structural insights will prove useful in engineering successful lectin
      therapeutics targeting the dense glycan shield of HIV.

PMID- 28434919
TI  - A review of DTCA techniques: Appraising their success and potential impact on
      medication users.
AB  - BACKGROUND: Direct-to-consumer advertising (DTCA) has been present in some
      countries for nearly two decades. Its success and ramifications have been
      examined but not yet cataloged recently in a comprehensive manner. OBJECTIVE: To
      review existing literature studies on the topic of DTCA techniques to provide an
      analysis of the current methods considered by drug marketers to enhance the
      effect of pharmaceutical product promotion and its success, as well as examine
      ramifications on the drug use process. METHODS: A search of 7 electronic
      databases including MEDLINE and SCOPUS was conducted in December 2015, and
      updated until February 2016. A scientific review of literature (2008-2015) was
      performed to identify and collate information from relevant, peer reviewed
      original study articles investigating various DTCA techniques commonly employed
      in pharmaceutical promotion. A thematic analysis was undertaken to categorize
      categories of drug promotion, or techniques, and the saliency and impact of
      these. RESULTS: Nineteen original study articles were included in this review.
      All articles were based in the U.S. and New Zealand, where DTCA is legal. After
      reviewing all the articles, 4 themes with 11 subcategories were generated. These
      themes included disease mongering and medicalization, drug references,
      advertisement strategies and eDTCA. The themes describe different categories of
      techniques used to augment DTC advertisements to increase their impact and
      overall success in promoting a pharmaceutical product. Many DTCA techniques
      utilized by pharmaceutical marketers are beneficial to the success of DTC
      promotion of a drug. These techniques include the use of drug efficacy
      information, comparative claims, non-branded help seeking advertisements,
      formatted risks information, celebrity or expert endorsers and website trust
      factors. Through their use, public perception of the drug is made more favorable,
      increased attention is drawn to the advertisement, and the pharmaceutical product
      gains greater credibility and subsequent success in sales. However some
      techniques, although beneficial to pharmaceutical promotion, need to be monitored
      by policymakers and regulatory advisors, as they have the potential to negatively
      impact consumer health knowledge. CONCLUSION: Overall, through this review it is
      evident that there are a number if techniques that employed by pharmaceutical
      marketers to augment the success of pharmaceutical promotion. While these
      techniques may be beneficial to pharmaceutical companies and might increase
      awareness amongst consumers, it is important to be critical of them, as they have
      the potential to be exploited by pharmaceutical marketers. This review indicated
      that although some techniques are successful and appear to be satisfactory in
      providing information to consumers, other techniques need to be appraised more
      closely.

PMID- 28434920
TI  - Corrigendum to "Characterization of a new alpha-l-fucosidase isolated from
      Fusarium proliferatum LE1 that is regioselective to alpha-(1 -> 4)-l-fucosidic
      linkage in the hydrolysis of alpha-l-fucobiosides" [Biochimie 132C (2017) 54-65].

PMID- 28434921
TI  - Identification of a novel and functional mutation in the TBX5 gene in a patient
      by screening from 354 patients with isolated ventricular septal defect.
AB  - Ventricular septal defect (VSD) is the most frequently occurring congenital heart
      disease in newborns. A number of genetic studies have linked TBX5 mutations to
      cardiac abnormalities. We aimed to identify potential pathogenic mutations in
      TBX5 and to provide insights into the etiology of sporadic and isolated VSD. Case
      control mutational and functional analyses were performed in 354 sporadic
      patients with isolated VSD and 341 controls. All the coding exons and intron-exon
      boundaries of TBX5 were first sequenced in a group of VSD patients and controls.
      Sanger sequencing with high-resolution melting (HRM) curve analysis in new
      patients and controls was then used to detect TBX5 mutation and frequency.
      Luciferase activities were measured to identify transcriptional regulation of
      TBX5 to MYH6 and ANF promoter. A novel heterozygous missense mutations c.40C > A
      (p.Pro14Thr) was identified in TBX5 gene exon-2, resulting proline to threonine
      substitution. TBX5 containing mutation reduced transcriptional activities of the
      MYH6 promoter but enhanced transcriptional activities of the ANF promoter,
      compared with the wild type. This novel heterozygous missense mutation in TBX5
      gene exon-2 that causes significant changes of the activity of TBX5 is therefore
      highly possible to be the cause of the defect in the VSD patients.

PMID- 28434922
TI  - Association of autoimmune thyroiditis and celiac disease with Juvenile Polyposis
      due to 10q23.1q23.31 deletion: Potential role of PI3K/Akt pathway dysregulation.
AB  - Juvenile Polyposis (JP) is a rare hereditary condition characterized by diffuse
      hamartomatous gastrointestinal polyposis, associated with a significantly
      increased risk of neoplastic transformation. Most of the cases are caused by SMAD
      and BMPR1A mutations, while 10q23 microdeletions, encompassing both PTEN and
      BMPR1A oncogenes, are extremely rare, typically associated with more aggressive
      JP, and extraintestinal features overlapping with PTEN Hamartoma Tumor Syndrome.
      We present the first case of a young female with multiple autoimmune disorders
      (i.e. thyroiditis and celiac disease), associated with JP, cardiac defects and
      epilepsy, who carries a de novo heterozygous 10q23.1q23.31 deletion. The
      dysregulation of the PI3K/Akt pathway is advanced as the putative mechanism
      connecting autoimmune, malformative and neoplastic disorders. A literature review
      of clinical manifestation, gene alterations and the treatment of patients with
      10q23 deletion is also provided, highlighting the importance of comprehensive,
      long-term, multi-disciplinary management, aimed at early identification and
      treatment of both intestinal and extraintestinal disorders.

PMID- 28434923
TI  - Deciphering the mechanism of Huang-Lian-Jie-Du-Decoction on the treatment of
      sepsis by formula decomposition and metabolomics: Enhancement of cholinergic
      pathways and inhibition of HMGB-1/TLR4/NF-kappaB signaling.
AB  - Sepsis is the major cause of morbidity and mortality in surgical patients. Huang
      Lian-Jie-Du-Decoction (HLJDD), a well-known Chinese herb formula, has long been
      used for the treatment of sepsis. In this investigation, by leaving one herb out
      each time, the four component herbs of HLJDD were reformulated to four HLJDD
      variants Form1-4, corresponding to the removal of Phellodendri Chinensis Cortex,
      Scutellariae Radix, Gardeniae Fructu and Coptidis Rhizoma, respectively.
      Metabolomics approach combined with histological inspection, biochemical
      measurement and molecular biology was used to investigate the treatment effects
      of HLJDD and its four variants on cecal ligation and puncture (CLP) model of
      sepsis, which were compared to decipher the formulating principles of HLJDD. Our
      results showed that HLJDD exhibit the strongest therapeutic effects in the CLP
      models as compared with the four variants, which could be ascribed to its most
      significant enhancement of cholinergic anti-inflammatory pathway and inhibition
      of HMGB-1/TLR4/NF-kappaB signaling pathway. Most of all, metabolites changed
      specifically between groups of HLJDD and its four variants were related with the
      exceptional treatment effects of HLJDD.

PMID- 28434925
TI  - Mature cystic teratomas of the ovary-reply.

PMID- 28434924
TI  - Tumor thickness and histological features as predictors of invasive foci within
      preoperatively diagnosed ductal carcinoma in situ.
AB  - Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in
      resected breast specimens. To disclose useful markers predictive of invasive foci
      within preoperatively diagnosed DCIS lesions, a retrospective histopathological
      comparison was made between postoperatively diagnosed invasive ductal carcinoma
      with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82).
      Through a multivariate logistic regression analysis model, 5 variables (DCIS
      grade, "tumor thickness," extent of retraction cleft, presence of lymph node
      metastasis, and HER2 score) were found to be significantly associated with the
      presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity,
      specificity, positive predictive value, and negative predictive value were 0.93,
      0.77, 0.68, and 0.95, respectively. No statistically significant difference was
      observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the
      IDCPIC curve showed a slightly earlier decline than the DCIS one. In general,
      preoperative detection of lymph node metastasis in DCIS patients is elusive
      because of the extremely tiny metastatic size in most cases; thus, a 4-variable
      model, without lymph node metastasis, would be the actual working model.
      Furthermore, tumor "thickness" was found to be the most significant parameter
      predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed
      similar recurrence-free survival curves, prediction of invasive foci within DCIS
      necessitates postoperative pathological analysis of surgically resected lesions.

PMID- 28434926
TI  - Scoping review to develop common data elements for lumbar spinal stenosis.
AB  - BACKGROUND CONTEXT: Common data elements (CDE) represent an important tool for
      understanding and classifying health outcomes across settings. Although CDEs have
      been developed for a number of disorders, to date CDEs for lumbar spinal stenosis
      (LSS) have not been fully developed. To facilitate the identification of CDEs and
      measures to assess them, this technical study leverages the International
      Classification of Functioning, Disability and Health (ICF), peer-reviewed
      research, and a panel of experts to identify CDEs specific to LSS. PURPOSE: The
      study aimed to define CDEs for disease characteristics and outcomes of LSS using
      the World Health Organization's ICF taxonomy, and to facilitate the selection of
      assessment instruments for research and clinical care. DESIGN: This is a scoping
      review using a modified Delphi approach with a technical expert panel composed of
      clinicians and scientists representing the academia, policy and advocacy
      stakeholders, and professional associations with expertise in LSS. METHODS: This
      is a scoping review to identify measures that assess LSS symptoms. Thirty-one
      subject matter experts (SMEs) prioritized ICF codes and evaluated instruments
      measuring specific domains. We used a modified Delphi technique to evaluate item
      level content and achieve consensus. RESULTS: SMEs prioritized 53 ICF codes; 3
      received 100% endorsement, 27 received >=90% endorsement, whereas the remaining
      23 received >=80% endorsement. Prioritized ICF codes represent diverse domains,
      including pain, activities and participation, and emotional well-being. The
      review yielded 58 instruments; we retained 24 for content analysis. CONCLUSIONS:
      The retained instruments adequately represent the ICFs activities and
      participation, and body function domains. Body structure and environmental
      factors were assessed infrequently. Adoption of these CDEs may guide clinical
      decision making and facilitate comparative effectiveness trials for interventions
      focused on LSS.

PMID- 28434927
TI  - Impact of Autologous Stem Cell Transplantation on the Incidence and Outcome of
      Oligoclonal Bands in Patients with Light-Chain Amyloidosis.
AB  - The emergence of oligoclonal bands (OB) in patients with multiple myeloma
      achieving a complete remission (CR) after autologous stem cell transplantation
      (ASCT) and the use of novel agents is a well-recognized event. The presence of OB
      is associated with favorable outcome. However, the emergence of OB in light-chain
      (AL) amyloidosis has never been investigated. The aim of the study was to
      determine the incidence, natural history, and prognostic impact of OB in 50
      patients with AL amyloidosis who achieved at least a partial response either
      after upfront ASCT (20 patients [40%]) or after conventional treatment in
      patients ineligible for transplantation (30 patients [60%]). OB were observed in
      60% of the patients, with IgG-kappa (30.7%) the most frequently detected isotype.
      This phenomenon was more prevalent in patients achieving CR than those in other
      response categories (88% versus 32%, P = .0001). The landmark analysis at 1 year
      after diagnosis demonstrates a significantly longer progression-free survival and
      an improvement trend in overall survival (P = .04 and P = .06, respectively).
      This prognostic impact was also observed in patients who achieved CR and in
      patients with more advanced stage. In summary, this is the first report of OB in
      patients with AL amyloidosis. Although its biological meaning remains unclear, it
      could reflect a more robust humoral immune response.

PMID- 28434928
TI  - Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone
      Chemotherapy in Mantle Cell Lymphoma Patients Is Associated with Higher Rates of
      Hematopoietic Progenitor Cell Mobilization Failure despite Plerixafor Rescue.
AB  - Induction regimens for mantle cell lymphoma (MCL) can be categorized into highly
      intensive regimens containing cytarabine and less intense regimens, such as
      rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R
      CHOP) or rituximab with bendamustine (R-bendamustine). Prior publications have
      shown rituximab and hyperfractionated cyclophosphamide, vincristine, doxorubicin,
      and dexamethasone (R-hyperCVAD) can be associated with stem cell mobilization
      failures. However, those studies did not include the use of plerixafor as rescue
      for stem cell mobilization failure. We examined our database of 181 consecutive
      MCL patients who received upfront therapy from 2005 to 2015 with either R
      hyperCVAD or less intense chemotherapy (R-bendamustine and R-CHOP only) regimens
      to assess impact of frontline chemotherapy on collection of hematopoietic cell
      progenitors before autologous stem cell transplantation (ASCT). In the
      preplerixafor era (before August 16, 2009), a significant difference in
      peripheral blood stem cell (PBSC) collection failure between the R-hyperCVAD
      (12%) and other chemotherapy (11%) groups was not established. However, in the
      postplerixafor era, use of R-hyperCVAD chemotherapy was associated with
      significantly higher rates of hematopoietic progenitor cell collection failures
      (17%) compared with that observed in the other chemotherapy group (4%; P = .04).
      The rates of mobilization failure declined to 4% in the postplerixafor era from
      11% in the preplerixafor era for patients receiving less intensive chemotherapy.
      Conversely, the rate of mobilization failure increased in the R-hyperCVAD group
      from 12% in the preplerixafor era to 17% in the postplerixafor era. Plerixafor
      does not overcome the negative impact of R-hyperCVAD on PBSC mobilization, and
      caution is warranted in using R-hyperCVAD in patients with newly diagnosed MCL
      who are candidates for ASCT.

PMID- 28434929
TI  - Rising to the Challenge of promoting research in primary care and nursing:
      Research productivity and professional view.
AB  - OBJECTIVE: To analyze the evolution of scientific production in a privately
      managed public institution, and to explore the perceptions of primary healthcare
      professionals with regard to research. METHOD: The institution includes a
      university hospital and 10 primary health centres, 673 physicians, and 747
      nurses. A bibliometric analysis on scientific production was performed. A
      questionnaire was designed, with 5 sections (sociodemographic data, competences,
      needs, motivation and satisfaction s with research) and 40 items (scale of 1-10).
      Its understanding, pertinence and validity of content were analyzed. RESULTS: In
      2014, the contribution of primary care to research accounted for 2.8% of the
      total impact factor of publications, and 4.8% of clinical trials. Nurses
      accounted for 0.6% of the impact factor, having published articles in first
      quartile journals. A total of 110(51%) primary care professionals participated in
      the survey. The average motivation for research was 7.85 points and satisfaction
      with research 4.37 points. The interest in receiving training in research (8.46
      points) was highlighted as well as the lack of leadership in research (2.93
      points). Regarding competences, research in teams was highlighted (6.87 points),
      and obtaining funding was noted as a negative (3.44 points). CONCLUSIONS:
      Research is experiencing a surge in all institutions, especially in hospitals.
      The primary care professionals expressed their motivation towards research and
      their dissatisfaction with the difficulties encountered, especially in obtaining
      funds.

PMID- 28434930
TI  - Enhancing targeted antibiotic therapy via pH responsive solid lipid nanoparticles
      from an acid cleavable lipid.
AB  - An acid cleavable lipid (SA-3M) was synthesized and used to develop pH-responsive
      solid lipid nanoparticles (SLNs) to deliver vancomycin base (VM-FB) to acidic
      infection sites. The size, polydispersity index and zeta potential of VM-FB_SA
      3M_SLNs were 132.9+/-9.1nm, 0.159+/-0.01 and -26+/-4.4mV respectively, with
      57.80+/-1.1% encapsulation efficiency. VM-FB release was significantly faster at
      pH6.5 than pH7.4. In vitro antibacterial activity against methicillin-susceptible
      and resistant Staphylococcus aureus (MSSA and MRSA) revealed that SLNs had
      enhanced activity at pH6.5 than pH7.4. In vivo study showed that the amount of
      MRSA remaining in the skin of VM-FB_SA-3M_SLNs treated mice was approximately 22
      fold lower than VM-FB treated mice. Histological investigations revealed that
      signs of inflammation in the skin treated with VM-FB_SA-3M_SLNs were minimal. In
      conclusion, this study confirmed that SA-3M can form pH-responsive SLNs capable
      of releasing antibiotic specifically at acidic infection sites.

PMID- 28434931
TI  - Effect of size and pegylation of liposomes and peptide-based synthetic
      lipoproteins on tumor targeting.
AB  - Synthetic high-density lipoprotein nanoparticles (sHDL) are a valuable class of
      nanomedicines with established animal safety profile, clinical tolerability and
      therapeutic efficacy for cardiovascular applications. In this study we examined
      how the scavenger receptor B-I-mediated (SR-BI) tumor-targeting ability of sHDL,
      long plasma circulation half-life, and small particle size (9.6+/-0.2nm) impacted
      sHDL accumulation in SR-BI positive colorectal carcinoma cells, 3D tumor
      spheroids, and in vivo xenografts. We compared tumor accumulation of sHDL with
      that of liposomes (LIP, 130.7+/-0.8nm), pegylated liposomes (PEG-LIP, 101+/-2nm),
      and pegylated sHDL (12.1+/-0.1nm), all prepared with the same lipid components.
      sHDL penetrated deep (210MUm) into tumor spheroids and exhibited 12- and 3-fold
      higher in vivo solid tumor accumulation, compared with LIP (p<0.01) and PEG-LIP
      (p<0.05), respectively. These results suggest that sHDL with established human
      safety possess promising intrinsic tumor-targeted properties.

PMID- 28434932
TI  - Combinatorial treatment of idiopathic pulmonary fibrosis using nanoparticles with
      prostaglandin E and siRNA(s).
AB  - Inhalation delivery of prostaglandin E (PGE2) in combination with selected
      siRNA(s) was proposed for the efficient treatment of idiopathic pulmonary
      fibrosis (IPF). Nanostructured lipid carriers (NLC) were used as a delivery
      system for PGE2 with and without siRNAs targeted to MMP3, CCL12, and HIF1Alpha
      mRNAs. The model of IPF was developed in SKH1 mice by intratracheal
      administration of bleomycin at a dose of 1.5U/kg. Results showed that NLC-PGE2 in
      combination with three siRNAs delivered locally to the lungs by inhalation
      markedly reduced mouse body mass, substantially limited hydroxyproline content in
      the lungs and disturbances of the mRNAs and protein expression, restricted lung
      tissue damage and prevented animal mortality. Our data provide evidence that IPF
      can be effectively treated by inhalation of the NLC-PGE2 in combination with
      siRNAs delivered locally into the lungs. This effect could not be achieved by
      using NLC containing just PGE2 or siRNA(s) alone.

PMID- 28434933
TI  - Assessing the Eligibility Criteria in Phase III Randomized Controlled Trials of
      Drug Therapy in Heart Failure With Preserved Ejection Fraction: The Critical Play
      Off Between a "Pure" Patient Phenotype and the Generalizability of Trial
      Findings.
AB  - AIMS: To investigate the effect of the different eligibility criteria used by
      phase III clinical studies in heart failure with preserved ejection fraction
      (HFpEF) on patient selection, phenotype, and survival. METHODS AND RESULTS: We
      applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis
      Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure
      and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People
      With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic
      Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac
      Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of
      LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure
      Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and
      well-characterized HFpEF population (n = 557) seen in modern European
      cardiological practice. Follow-up was available for a minimum of 24 months in
      each patient. Increasing the number of study eligibility criteria identifies a
      progressively smaller group of patients from real-life practice suitable for
      recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic
      patients would have been eligible, whereas the PARAGON-HF criteria significantly
      reduced this proportion to 32%. The patients identified from our clinical
      population had similar mortality rates using the different criteria, which were
      consistently higher than those reported in the actual clinic trials. CONCLUSIONS:
      Trial eligibility criteria have become stricter with time, which reduces the
      number of eligible patients, affecting both generalizability of any findings and
      feasibility of completing an adequately powered trial. We could not find evidence
      that the additional criteria used in more recent randomized trials in HFpEF have
      identified patients at higher risk of all-cause mortality.

PMID- 28434934
TI  - Introducing a novel gravitation-based high-velocity compaction analysis method
      for pharmaceutical powders.
AB  - With modern tableting machines large amounts of tablets are produced with high
      output. Consequently, methods to examine powder compression in a high-velocity
      setting are in demand. In the present study, a novel gravitation-based method was
      developed to examine powder compression. A steel bar is dropped on a punch to
      compress microcrystalline cellulose and starch samples inside the die. The
      distance of the bar is being read by a high-accuracy laser displacement sensor
      which provides a reliable distance-time plot for the bar movement. In-die height
      and density of the compact can be seen directly from this data, which can be
      examined further to obtain information on velocity, acceleration and energy
      distribution during compression. The energy consumed in compact formation could
      also be seen. Despite the high vertical compression speed, the method was proven
      to be cost-efficient, accurate and reproducible.

PMID- 28434935
TI  - Solid nanofoams based on cellulose nanofibers and indomethacin-the effect of
      processing parameters and drug content on material structure.
AB  - The unique colloidal properties of cellulose nanofibers (CNF), makes CNF a very
      interesting new excipient in pharmaceutical formulations, as CNF in combination
      with some poorly-soluble drugs can create nanofoams with closed cells. Previous
      nanofoams, created with the model drug indomethacin, demonstrated a prolonged
      release compared to films, owing to the tortuous diffusion path that the drug
      needs to take around the intact air-bubbles. However, the nanofoam was only
      obtained at a relatively low drug content of 21wt% using fixed processing
      parameters. Herein, the effect of indomethacin content and processing parameters
      on the foaming properties was analysed. Results demonstrate that a certain amount
      of dissolved drug is needed to stabilize air-bubbles. At the same time, larger
      fractions of dissolved drug promote coarsening/collapse of the wet foam. The
      pendant drop/bubble profile tensiometry was used to verify the wet-foam stability
      at different pHs. The pH influenced the amount of solubilized drug and the
      processing-window was very narrow at high drug loadings. The results were
      compared to real foaming-experiments and solid state analysis of the final
      cellular solids. The parameters were assembled into a processing chart,
      highlighting the importance of the right combination of processing parameters (pH
      and time-point of pH adjustment) in order to successfully prepare cellular solid
      materials with up to 46 wt% drug loading.

PMID- 28434936
TI  - Defining a Research Agenda to Address the Converging Epidemics of Tuberculosis
      and Diabetes: Part 1: Epidemiology and Clinical Management.
AB  - There is growing interest in the interaction between type 2 diabetes mellitus
      (DM) and TB, but many research questions remain unanswered. Epidemiologists,
      basic scientists, and clinical experts recently convened and identified
      priorities. This is the first of two reviews on this topic, summarizing priority
      areas of research regarding epidemiology, clinical management, and public health.
      First, from an epidemiologic point of view, more study is needed to determine the
      importance of transient hyperglycemia in patients with TB and on the importance
      of DM for the global epidemic of multidrug resistant (MDR)-TB. Second, regarding
      the screening and clinical management of combined TB and DM (TB-DM), clinical
      trials and large cohort studies should examine the benefits of improved DM care
      as well as prolonged or intensified TB treatment on the outcome of TB-DM and
      investigate the cost-effectiveness of screening methods for DM among patients
      newly diagnosed with TB. Third, from a public health and health systems point of
      view, the population health impact and cost-effectiveness of different
      interventions to prevent or treat DM and TB in high-burden populations should be
      examined, and health-system interventions should be developed for routine TB-DM
      screening, management of DM after completion of TB treatment, and better access
      to DM services worldwide. Studies are needed across different ethnicities and
      settings given the heterogeneity of metabolic perturbations, inflammatory
      responses, medications, and access to health care. Finally, studies should
      address interactions between TB, DM, and HIV because of the convergence of
      epidemics in sub-Saharan Africa and some other parts of the world.

PMID- 28434937
TI  - Defining a Research Agenda to Address the Converging Epidemics of Tuberculosis
      and Diabetes: Part 2: Underlying Biologic Mechanisms.
AB  - There is growing interest in the re-emerging interaction between type 2 diabetes
      (DM) and TB, but the underlying biologic mechanisms are poorly understood despite
      their possible implications in clinical management. Experts in epidemiologic,
      public health, basic science, and clinical studies recently convened and
      identified research priorities for elucidating the underlying mechanisms for the
      co-occurrence of TB and DM. We identified gaps in current knowledge of altered
      immunity in patients with DM during TB, where most studies suggest an
      underperforming innate immunity, but exaggerated adaptive immunity to
      Mycobacterium tuberculosis. Various molecular mechanisms and pathways may
      underlie these observations in the DM host. These include signaling induced by
      excess advanced glycation end products and their receptor, higher levels of
      reactive oxidative species and oxidative stress, epigenetic changes due to
      chronic hyperglycemia, altered nuclear receptors, and/or differences in cell
      metabolism (immunometabolism). Studies in humans at different stages of DM (no
      DM, pre-DM, and DM) or TB (latent or active TB) should be complemented with
      findings in animal models, which provide the unique opportunity to study early
      events in the host-pathogen interaction. Such studies could also help identify
      biomarkers that will complement clinical studies in order to tailor the
      prevention of TB-DM, or to avoid the adverse TB treatment outcomes that are more
      likely in these patients. Such studies will also inform new approaches to host
      directed therapies.

PMID- 28434938
TI  - Polycomb Group Gene E(z) Is Required for Spermatogonial Dedifferentiation in
      Drosophila Adult Testis.
AB  - Dedifferentiation is an important process to replenish lost stem cells during
      aging or regeneration after injury to maintain tissue homeostasis. Here, we
      report that Enhancer of Zeste [E(z)], a component of the Polycomb repression
      complex 2 (PRC2), is required to maintain a stable pool of germline stem cells
      (GSCs) within the niche microenvironment. During aging, germ cells with reduced
      E(z) activity cannot meet that requirement, but the defect arises from neither
      increased GSC death nor premature differentiation. Instead, we found evidence
      that the decrease of GSCs upon the inactivation of E(z) in the germline could be
      attributed to defective dedifferentiation. During recovery from genetically
      manipulated GSC depletion, E(z) knockdown germ cells also fail to replenish lost
      GSCs. Taken together, our data suggest that E(z) acts intrinsically in germ cells
      to activate dedifferentiation and thus replenish lost GSCs during both aging and
      tissue regeneration.

PMID- 28434939
TI  - Calreticulin Is Required for TGF-beta-Induced Epithelial-to-Mesenchymal
      Transition during Cardiogenesis in Mouse Embryonic Stem Cells.
AB  - Calreticulin, a multifunctional endoplasmic reticulum resident protein, is
      required for TGF-beta-induced epithelial-to-mesenchymal transition (EMT) and
      subsequent cardiomyogenesis. Using embryoid bodies (EBs) derived from
      calreticulin-null and wild-type (WT) embryonic stem cells (ESCs), we show that
      expression of EMT and cardiac differentiation markers is induced during
      differentiation of WT EBs. This induction is inhibited in the absence of
      calreticulin and can be mimicked by inhibiting TGF-beta signaling in WT cells.
      The presence of calreticulin in WT cells permits TGF-beta-mediated signaling via
      AKT/GSK3beta and promotes repression of E-cadherin by SNAIL2/SLUG. This is
      paralleled by induction of N-cadherin in a process known as the cadherin switch.
      We show that regulated Ca2+ signaling between calreticulin and calcineurin is
      critical for the unabated TGF-beta signaling that is necessary for the exit from
      pluripotency and the cadherin switch during EMT. Calreticulin is thus a key
      mediator of TGF-beta-induced commencement of cardiomyogenesis in mouse ESCs.

PMID- 28434940
TI  - Prospective Isolation and Comparison of Human Germinal Matrix and Glioblastoma
      EGFR+ Populations with Stem Cell Properties.
AB  - Characterization of non-neoplastic and malignant human stem cell populations in
      their native state can provide new insights into gliomagenesis. Here we developed
      a purification strategy to directly isolate EGFR+/- populations from human
      germinal matrix (GM) and adult subventricular zone autopsy tissues, and from de
      novo glioblastoma (GBM) resections, enriching for cells capable of binding EGF
      ligand (LBEGFR+), and uniquely compared their functional and molecular
      properties. LBEGFR+ populations in both GM and GBM encompassed all sphere-forming
      cells and displayed proliferative stem cell properties in vitro. In xenografts,
      LBEGFR+ GBM cells showed robust tumor initiation and progression to high-grade,
      infiltrative gliomas. Whole-transcriptome sequencing analysis confirmed
      enrichment of proliferative pathways in both developing and neoplastic freshly
      isolated EGFR+ populations, and identified both unique and shared sets of genes.
      The ability to prospectively isolate stem cell populations using native ligand
      binding capacity opens new doors onto understanding both normal human development
      and tumor cell biology.

PMID- 28434941
TI  - Dysregulation of the SIRT1/OCT6 Axis Contributes to Environmental Stress-Induced
      Neural Induction Defects.
AB  - Environmental stresses are increasingly acknowledged as core causes of abnormal
      neural induction leading to neural tube defects (NTDs). However, the mechanism
      responsible for environmental stress-triggered neural induction defects remains
      unknown. Here, we report that a spectrum of environmental stresses, including
      oxidative stress, starvation, and DNA damage, profoundly activate SIRT1, an NAD+
      dependent lysine deacetylase. Both mouse embryos and in vitro differentiated
      embryonic stem cells (ESCs) demonstrated a negative correlation between the
      expression of SIRT1 and that of OCT6, a key neural fate inducer. Activated SIRT1
      radically deacetylates OCT6, triggers an OCT6 ubiquitination/degradation cascade,
      and consequently increases the incidence of NTD-like phenotypes in mice or
      hinders neural induction in both human and mouse ESCs. Together, our results
      suggest that early exposure to environmental stresses results in the
      dysregulation of the SIRT1/OCT6 axis and increases the risk of NTDs.

PMID- 28434942
TI  - iPSC-Derived Regulatory Dendritic Cells Inhibit Allograft Rejection by Generating
      Alloantigen-Specific Regulatory T Cells.
AB  - Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic
      tool for transplant rejection. We generated DCregs from murine induced
      pluripotent stem cells (iPSCs), which could remain in a "stable immature stage"
      even under strong stimulation. Harnessing this characteristic, we hypothesized
      that iPS-DCregs worked as a negative vaccine to generate regulatory T cells
      (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA
      (H-2Kk) mice with B6 (H-2Kb) iPS-DCregs and found that Tregs (CD4+CD25+FOXP3+)
      significantly increased in CBA splenocytes. Moreover, immunized CBA recipients
      permanently accepted B6 cardiac grafts in a donor-specific pattern. We
      demonstrated mechanistically that donor-type iPS-DCregs triggered transforming
      growth factor beta1 secretion, under which the donor-antigen peptides directed
      naive CD4+ T cells to differentiate into donor-specific FOXP3+ Tregs instead of
      into effector T cells in vivo. These findings highlight the potential of iPS
      DCregs as a key cell therapy resource in clinical transplantation.

PMID- 28434943
TI  - Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress
      Related Pathogenesis and Current Challenges in Biomarker Development.
AB  - HPA axis genes implicated in glucocorticoid regulation play an important role in
      regulating the physiological impact of social and environmental stress, and have
      become a focal point for investigating the role of glucocorticoid regulation in
      the etiology of disease. We conducted a systematic review to critically assess
      the full range of clinical associations that have been reported in relation to
      DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5,
      and HSD11beta1/2 genes in adults. A total of 32 studies were identified. There is
      prospective evidence for an association between HSD11beta2 methylation and
      hypertension, and functional evidence of an association between NR3C1 methylation
      and both small cell lung cancer (SCLC) and breast cancer. Strong associations
      have been reported between FKBP5 and NR3C1 methylation and PTSD, and biologically
      plausible associations have been reported between FKBP5 methylation and
      Alzheimer's Disease. Mixed associations between NR3C1 methylation and mental
      health outcomes have been reported according to different social and
      environmental exposures, and according to varying gene regions investigated. We
      conclude by highlighting key challenges and future research directions that will
      need to be addressed in order to develop both clinically meaningful prognostic
      biomarkers and an evidence base that can inform public policy practice.

PMID- 28434944
TI  - Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV
      Immunization.
AB  - BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to
      test Ebola vaccine candidates. As part of the World Health Organisation-led VSV
      Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating
      rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine),
      which has recently demonstrated protection from Ebola virus disease (EVD) in
      phase III clinical trials and is currently in advanced stages of licensing. So
      far, correlates of immune protection are incompletely understood and the role of
      cell-mediated immune responses has not been comprehensively investigated to date.
      METHODS: We recruited 30 healthy subjects aged 18-55 into an open-label, dose
      escalation phase I trial testing three doses of rVSV-ZEBOV (3*105 plaque-forming
      units (PFU), 3*106 PFU, 2*107 PFU) (ClinicalTrials.gov; NCT02283099). Main study
      objectives were safety and immunogenicity, while exploratory objectives included
      lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were
      assessed using flow cytometry, ELISpot and LUMINEX assay. FINDINGS: Immunization
      with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse
      events. Ebola virus-specific neutralizing antibodies were induced in nearly all
      individuals. Additionally, vaccinees, particularly within the highest dose
      cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a
      cascade of signaling molecules following stimulation of peripheral blood
      mononuclear cells with Ebola GP peptides. INTERPRETATION: In addition to a benign
      safety and robust humoral immunogenicity profile, subjects immunized with 2*107
      PFU elicited higher cellular immune responses and stronger interlocked cytokine
      networks compared to lower dose groups. To our knowledge these data represent the
      first detailed cell-mediated immuneprofile of a clinical trial testing rVSV
      ZEBOV, which is of particular interest in light of its potential upcoming
      licensure as the first Ebola vaccine. VEBCON trial Hamburg, Germany
      (NCT02283099).

PMID- 28434947
TI  - Effect of Urinary Cytology for Detecting Recurrence in Remnant Urothelium After
      Radical Cystectomy: Insights From a 10-year Cytology Database.
AB  - BACKGROUND: We evaluated the diagnostic accuracy of urinary cytology (UCy) for
      detecting recurrence in the remnant urothelium (RRU) after radical cystectomy
      (RC) for urothelial cancer. PATIENTS AND METHODS: We conducted a 10-year
      retrospective analysis of a prospectively collected, single-center RC database
      comprising 177 patients who had undergone follow-up examinations at our
      department with >= 1 available postoperative UCy specimen. UCy specimens were
      classified using the Papanicolaou scheme. RESULTS: In total, 957 cytology
      specimens were collected. Negative UCy results were noted in 927 (96.8%),
      atypical urothelial cells in 19 (2.0%), and suspicious/positive for malignancy in
      11 (1.2%) cases. RRU was diagnosed in 16 patients (9.1%) during a mean follow-up
      period of 37 months (range, 1-118 months). The mean interval from RC to RRU was
      34.7 months. Only 2 of 11 positive UCy specimens (18.2%) were falsely positive,
      for an overall sensitivity and specificity of 56.3% and 98.8% for predicting RRU,
      respectively. Urethral recurrence was diagnosed by UCy alone before the patients
      had developed symptoms in 8 of 12 cases (66.7%). Patients with clinical symptoms
      at the diagnosis of RRU had poorer cancer-specific survival rates than those of
      asymptomatic patients, although this trend was not statistically significant (P =
      .496). Moreover, positive UCy findings were associated with significantly lower
      overall survival (P < .001) and cancer-specific survival (P = .04) compared with
      negative UCy findings. CONCLUSION: Our results underline the predictive value of
      UCy in the surveillance of the remnant urothelium, with early detection of
      urethral recurrence before the development of clinical symptoms.

PMID- 28434945
TI  - Prognostic Biomarker Identification Through Integrating the Gene Signatures of
      Hepatocellular Carcinoma Properties.
AB  - Many molecular classification and prognostic gene signatures for hepatocellular
      carcinoma (HCC) patients have been established based on genome-wide gene
      expression profiling; however, their generalizability is unclear. Herein, we
      systematically assessed the prognostic effects of these gene signatures and
      identified valuable prognostic biomarkers by integrating these gene signatures.
      With two independent HCC datasets (GSE14520, N=242 and GSE54236, N=78), 30
      published gene signatures were evaluated, and 11 were significantly associated
      with the overall survival (OS) of postoperative HCC patients in both datasets.
      The random survival forest models suggested that the gene signatures were
      superior to clinical characteristics for predicting the prognosis of the
      patients. Based on the 11 gene signatures, a functional protein-protein
      interaction (PPI) network with 1406 nodes and 10,135 edges was established. With
      tissue microarrays of HCC patients (N=60), we determined the prognostic values of
      the core genes in the network and found that RAD21, CDK1, and HDAC2 expression
      levels were negatively associated with OS for HCC patients. The multivariate Cox
      regression analyses suggested that CDK1 was an independent prognostic factor,
      which was validated in an independent case cohort (N=78). In cellular models,
      inhibition of CDK1 by siRNA or a specific inhibitor, RO-3306, reduced cellular
      proliferation and viability for HCC cells. These results suggest that the
      prognostic predictive capacities of these gene signatures are reproducible and
      that CDK1 is a potential prognostic biomarker or therapeutic target for HCC
      patients.

PMID- 28434946
TI  - Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related
      Injury.
AB  - Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and
      fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted
      by infiltration of circulating macrophages. Monocyte chemoattractant protein-1
      (MCP-1) has been shown to attract macrophages in kidney diseases. P2X7 receptors
      (P2X7R) are highly expressed on macrophages and are essential components of pro
      inflammatory signaling in multiple tissues. Here we show that in diabetic
      patients, renal P2X7R expression is associated with severe mesangial expansion,
      impaired glomerular filtration (<=40ml/min/1.73sq.m.), and increased interstitial
      fibrosis. P2X7R activation enhanced the release of MCP-1 in human mesangial cells
      cultured under high glucose conditions. In mice, P2X7R-deficiency prevented
      glomerular macrophage attraction and collagen IV deposition; however, the more
      severe interstitial inflammation and fibrosis often seen in human diabetic kidney
      diseases was not modelled. Finally, we demonstrate that a P2X7R inhibitor
      (AZ11657312) can reduce renal macrophage accrual following the establishment of
      hyperglycemia in a model of diabetic nephropathy. Collectively these data suggest
      that P2X7R activation may contribute to the high prevalence of kidney disease
      found in diabetics.

PMID- 28434949
TI  - Maternal immune activation during pregnancy in rats impairs working memory
      capacity of the offspring.
AB  - Maternal immune activation during pregnancy is an environmental risk factor for
      psychiatric illnesses such as schizophrenia in the offspring. Patients with
      schizophrenia display an array of cognitive symptoms, including impaired working
      memory capacity. Rodent models have been developed to understand the relationship
      between maternal immune activation and the cognitive symptoms of schizophrenia.
      The present experiment was designed to test whether maternal immune activation
      with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy
      affects working memory capacity of the offspring. Pregnant Long Evans rats were
      treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male
      offspring of the litters (2-3months of age) were subsequently trained on a
      nonmatching-to-sample task with odors. After a criterion was met, the rats were
      tested on the odor span task, which requires rats to remember an increasing span
      of different odors to receive food reward. Rats were tested using delays of
      approximately 40s during the acquisition of the task. Importantly, polyI:C- and
      saline-treated offspring did not differ in performance of the nonmatching-to
      sample task suggesting that both groups could perform a relatively simple working
      memory task. In contrast, polyI:C-treated offspring had reduced span capacity in
      the middle and late phases of odor span task acquisition. After task acquisition,
      the rats were tested using the 40s delay and a 10min delay. Both groups showed a
      delay-dependent decrease in span, although the polyI:C-treated offspring had
      significantly lower spans regardless of delay. Our results support the validity
      of the maternal immune activation model for studying the cognitive symptoms of
      neurodevelopmental disorders such as schizophrenia.

PMID- 28434948
TI  - International and multidisciplinary expert recommendations for the use of
      biologics in systemic lupus erythematosus.
AB  - BACKGROUND/PURPOSE: Despite conventional immunosuppressants, active and steroid
      dependent systemic lupus erythematosus (SLE) represents a therapeutic challenge.
      Only one biologic, belimumab, has been approved, but other biologics are
      sometimes used off-label. Given the lack of evidence-based data in some clinical
      situations encountered in real life, we developed expert recommendations for the
      use of biologics for SLE. METHODS: The recommendations were developed by a formal
      consensus method. This method aims to formalize the degree of agreement among
      experts by identifying, through iterative ratings with feedback, the points on
      which experts agree, disagree or are undecided. Hence, the recommendations are
      based on the agreed-upon points. We gathered the opinion of 59 French-speaking
      SLE experts from 3 clinical networks dedicated to systemic autoimmune diseases
      (FLEUR, IMIDIATE, FAI2R) from Algeria, Belgium, France, Italy, Morocco,
      Switzerland and Tunisia. Represented medical specialities were internal medicine
      (49%), rheumatology (34%), nephrology (7%), dermatology (5%), pediatrics (3%) and
      cardiology (2%). Two methodologists and 3 strictly independent SLE expert groups
      contributed to developing these recommendations: a steering group (SG) (n=9), an
      evaluation group (EG) (n=28) and a reading group (RG) (n=22). Preliminary
      recommendations were drafted by the SG, then proposed to the EG. Each EG member
      rated the degree of agreement from 1 to 9 (1: lowest; 9: strongest) for each
      recommendation. After 2 rating rounds, the SG submitted a new version of the
      recommendations to the RG. With comments from the RG, the SG finalised the
      recommendations. RESULTS: A total of 17 final recommendations were formulated by
      the SG, considering all agreement scores and comments by the EG and RG members
      and the two methodologists. These recommendations define the subset of patients
      who require a biologic; the type of biologics to use (belimumab, rituximab, etc.)
      depending on the organ involvement and associated co-treatments; what information
      should be given to patients; and how to evaluate treatment efficacy and when to
      consider discontinuation. CONCLUSION: Overall, 17 recommendations for the good
      use of biologics in SLE were formulated by a large panel of SLE experts to
      provide guidance for clinicians in daily practice. These recommendations will be
      regularly updated according to the results of new randomized trials and
      increasing real life experience.

PMID- 28434950
TI  - An Arabidopsis Lipid Flippase Is Required for Timely Recruitment of Defenses to
      the Host-Pathogen Interface at the Plant Cell Surface.
AB  - Deposition of cell wall-reinforcing papillae is an integral component of the
      plant immune response. The Arabidopsis PENETRATION 3 (PEN3) ATP binding cassette
      (ABC) transporter plays a role in defense against numerous pathogens and is
      recruited to sites of pathogen detection where it accumulates within papillae.
      However, the trafficking pathways and regulatory mechanisms contributing to
      recruitment of PEN3 and other defenses to the host-pathogen interface are poorly
      understood. Here, we report a confocal microscopy-based screen to identify
      mutants with altered localization of PEN3-GFP after inoculation with powdery
      mildew fungi. We identified a mutant, aberrant localization of PEN3 3 (alp3),
      displaying accumulation of the normally plasma membrane (PM)-localized PEN3-GFP
      in endomembrane compartments. The mutant was found to be disrupted in the P4
      ATPase AMINOPHOSPHOLIPID ATPASE 3 (ALA3), a lipid flippase that plays a critical
      role in vesicle formation. We provide evidence that PEN3 undergoes continuous
      endocytic cycling from the PM to the trans-Golgi network (TGN). In alp3, PEN3
      accumulates in the TGN, causing delays in recruitment to the host-pathogen
      interface. Our results indicate that PEN3 and other defense proteins continuously
      cycle through the TGN and that timely exit of these proteins from the TGN is
      critical for effective pre-invasive immune responses against powdery mildews.

PMID- 28434951
TI  - Role of CRF1 receptor in post-incisional plasma extravasation and nociceptive
      responses in mice.
AB  - The corticotropin-releasing factor (CRF) is involved in a number of physiological
      functions including pain perception. The purpose of this study was to evaluate
      the role of CRF1 receptor in the long-lasting post-surgical changes in somatic
      nociceptive thresholds and in local inflammatory responses, using genetically
      engineered mice lacking functional CRF1 receptor. Animals underwent a plantar
      incision under anaesthesia with remifentanil (80MUg/kg s.c.) and sevoflurane.
      Mechanical thresholds (von Frey) and plasma extravasation (Evan's blue) were
      evaluated at different time points. On postoperative day 20, mechanical
      thresholds had returned to baseline in CD1 mice (3.07+/-6.21%), while
      B6,129CRHtklee mice presented significant hyperalgesia, which was similar in wild
      type (WT) (-29.81+/-8.89%) and CRF1 receptor knockout (KO) (-37.10+/-10.75%)
      mice, showing strain differences. The administration of naloxone (1mg/kg, s.c.)
      on postoperative day 21 produced hyperalgesia revealing surgery-induced latent
      pain sensitization. The extent of hyperalgesia was greater in KO versus WT mice,
      suggesting a role of CRF1 receptors in the upward modulation of endogenous opioid
      release. Furthermore, two days after surgery, plasma extravasation returned to
      baseline in WT mice but remained elevated in KO mice. In non-manipulated
      B6,129CRHtklee KO mice we observed an increase in the number of writhes (41.25+/
      11.36) versus WT (23.80+/-4.71), while in the tail immersion test no differences
      could be detected. Our results show that CRF/CRF1 receptors seem to be a
      protective role in latent pain sensitization induced by surgery and in the local
      inflammatory response to injury.

PMID- 28434952
TI  - Motor Outcomes After Surgical Resection of Lesions Involving the Motor Pathway: A
      Prognostic Evaluation Scale.
AB  - BACKGROUND: Preservation of function is essential in surgical resection of
      lesions involving the motor pathways. The aim of this work is to evaluate the
      effect of anatomic features of lesions located in the motor pathway on neurologic
      and functional outcome. We propose an evaluation score to assess the risk of
      postoperative worsening. METHODS: A total of 92 patients suffering from lesions
      involving the motor pathways have been studied for what concerns motor functions
      (muscular strength scale [MRC]) after surgical treatment. Patient-related,
      surgery-related, and lesion-related data were recorded to identify relations with
      motor outcomes. Cortical surfacing of the lesion and amount of millimeters of
      interface between the lesion and corticospinal tract have been investigated with
      preoperative magnetic resonance imaging sequences and tractographic
      reconstructions. RESULTS: Means of the MRC Scale preoperative and 7 days
      postoperative were 3.6 +/- 2.23 and 3.8 +/- 2.28 for the upper limbs, and 4.1 +/-
      2.31 and 4.4 +/- 2.33 for the lower limbs, respectively. Patients that were
      stable or improved at 7 days from surgery were 82.6%. The anatomic features
      investigated have been summed up in a single score (envelopment/surfacing [ES]).
      In cases of ES classes V and VI, a total cumulative predicted worsening rate was
      24.2% and 14.8%, respectively. The risk of worsening was 1.682 times greater for
      the higher ES classes (IV-VI). CONCLUSIONS: The anatomic features of lesions are
      crucial in the prediction of motor outcome. The new proposed score (ES score) is
      useful to stratify motor function prognosis.

PMID- 28434953
TI  - The Multiscope Technique for Microvascular Decompression.
AB  - BACKGROUND: Endoscopic surgery has rapidly become widespread in neurosurgery in
      recent years. Endoscopy can offer close and panoramic surgical views with fine
      illumination, even in the deep intracranial area. However, it also has the
      following serious drawback: an intracranial blind area between the field lens of
      the endoscope and the site of the dural opening. This blind area cannot be viewed
      on the endoscopic monitor, and several surgical complications, including
      accidental intracranial neurovascular structural injury, can occur in this area.
      In this article, we report a new multiscope surgical technique that can
      compensate for this serious disadvantage of endoscopic surgery. METHODS: In the
      multiscope technique, endoscopic and exoscopic systems are used simultaneously
      with 2 monitors. Microvascular decompression (MVD) is performed fully
      endoscopically using an exoscope that compensates for the intracranial blind area
      of the endoscopic view. Two high-definition monitors for the endoscope and
      exoscope are placed side-by-side in front of the primary surgeon. RESULTS: Two
      patients with hemifacial spasm were treated by endoscopic MVD with the multiscope
      technique. In these procedures, fine surgical views were obtained by both the
      endoscope and exoscope. Two monitors were placed side-by-side in front of the
      surgeon; as a result, the physician could easily view them simultaneously during
      the operation. No surgery-related complications occurred. CONCLUSIONS: The
      multiscope technique can facilitate the performance of safer neuroendoscopic
      surgery than conventional endoscopic surgery. This technique can also be adopted
      in other skull base surgeries, in which the importance of endoscopy is growing.

PMID- 28434954
TI  - Coronal Multiplane Reconstructed Computed Tomography Image Determining Lateral
      Vertebral Notch-Referred Pedicle Screw Entry Point in Subaxial Cervical Spine: A
      Preclinical Study.
AB  - OBJECTIVE: To evaluate feasibility of computed tomography (CT) coronal multiplane
      reconstruction image (CMRI) to determine subaxial cervical pedicle screw (PS)
      entry point and guide lateral vertebral notch (LVN)-referred technique for
      subaxial cervical PS insertion. METHODS: Cervical CT scans were performed in 40
      volunteers. PS entry point was determined by quantitating PS entry point related
      to LVN on CMRI. Pedicle mediolateral angle (alpha) and cephalocaudad angle (beta)
      were also measured to guide the trajectory of PS insertion. Based on these
      quantitations, 12 human cadaveric subaxial cervical pedicles were inserted with
      PS referring to LVN. Cortical integrity of each pedicle was evaluated after
      dissecting the cadaveric vertebrae one by one and confirmed by radiography and
      CT. The cortical penetration and PS position were classified into 4 grades: 0
      (excellent position), I (good position), II (fair position), and III (poor
      position). RESULTS: On CT CMRI, PS entry point was consistently located
      approximately 2.2 mm medial to LVN from C3 to C7 and approximately 1.4 mm lower
      to LVN from C3 to C6, but 1.2 mm higher at C7. Bilateral alpha angle and beta
      angle showed substantial decrease from cranial to caudal. Cortical integrity of
      PS positions was excellent and good in 88.33%, fair in 8.33%, and poor in 3.33%.
      CONCLUSIONS: CMRI is reliable for determining subaxial cervical PS entry point.
      LVN is a consistent landmark for the notch-referred technique, which is a
      practical and easy to master technique for subaxial cervical spine PS insertion.

PMID- 28434955
TI  - Arterial Hypertension Is Associated with Symptomatic Spinal Dural Arteriovenous
      Fistulas.
AB  - OBJECTIVE: To determine possible systemic factors that may induce or be
      associated with the pathogenesis and pathologic course of spinal dural
      arteriovenous fistulas (SDAVFs), the most common type of arteriovenous disorder
      of the spinal cord and its meninges. METHODS: We assessed the role of possible
      systemic (vascular) risk factors (arterial hypertension, diabetes mellitus, fat
      metabolism disorders, and nicotine dependence) by comparing the prevalence of
      these risk factors in an SDAVF cohort of 59 patients with the prevalence in the
      general population. RESULTS: Age-corrected prevalence of arterial hypertension in
      the SDAVF cohort was significantly higher than in the general population (P <
      0.001). Prevalence of diabetes mellitus (P = 0.150.), nicotine dependence (P =
      0.561), adiposity (P = 0.217), and fat metabolism disorders (P = 0.125) did not
      differ from prevalence of comparable cohorts in the general population.
      CONCLUSIONS: Our results and data from the literature suggest that arterial
      hypertension may play an important role in the development of SDAVF-related
      symptoms or the development of SDAVFs in the presence of other predisposing
      factors.

PMID- 28434956
TI  - Superficial Temporal Artery-Middle Cerebral Artery Bypass Surgery for Refractory
      Symptomatic Intracranial Atherosclerotic Stenosis.
AB  - OBJECTIVE: To evaluate blood flow changes after bypass surgery for refractory
      symptomatic intracranial atherosclerotic stenosis (ICAS). METHODS: We examined a
      cohort of consecutive patients with symptomatic ICAS. Superficial temporal artery
      middle cerebral artery (MCA) bypass was performed in refractory patients with
      poor perfusion. Angiograms were graded systematically for antegrade, collateral,
      and bypass flow, and clinical variables were collected preoperatively, at 7 days
      postoperatively, and 3, 6, and 12 months postoperatively. RESULTS: Among 185
      consecutive cases with ICAS, 15 patients who were unsuitable for or did not
      respond to the best medical therapy or stenting underwent bypass surgery. No
      patients had new ischemic deficits within 7 days postoperatively. The mean follow
      up period was 30.2 +/- 12.3 months. Within this period, all anastomoses were
      patent by methods of ultrasound or computed tomography angiography. In 2
      patients, stenotic lesions exhibited early postoperative occlusion conversion at
      7 days on digital subtraction angiography. In 2 patients, stenotic lesions showed
      progression of occlusion at 6 and 8 months. The 2 lesions with early occlusion
      were both located in the MCA. The extent of retrograde blood flow via bypass
      anastomosis was correlated with early occlusion conversion. CONCLUSIONS: For
      refractory ICAS in patients with compromised hemodynamics, direct bypass might
      induce early occlusion of a stenotic area. MCA lesions may have a greater
      tendency toward early occlusion conversion.

PMID- 28434957
TI  - Amygdalohippocampectomy via the Lateral Extended Transsphenoidal Endoscopic
      Approach Through the Pterygopalatine Fossa: An Anatomic Study.
AB  - BACKGROUND: The lateral extended transsphenoidal endoscopic approach (LETEA) is
      used to remove tumors located lateral to the cavernous segment of the internal
      carotid artery under direct visual control and provides access to Meckel cave,
      pterygopalatine fossa, medial part of the middle cranial fossa, and orbit. We
      describe an extended transsphenoidal approach to the amygdalohippocampectomy
      through the pterygopalatine fossa. METHODS: The LETEA to the middle cranial fossa
      through the pterygopalatine fossa was studied on 3 injected human cadavers at the
      Burdenko Neurosurgery Institute in Moscow, Russia. RESULTS: LETEA and trepanation
      of the greater wing of the sphenoid bone allow access to the medial part of the
      middle cranial fossa. Medial segments of the temporal lobe (hippocampus and
      amygdala) and the temporal pole were removed under guidance of the 45 degrees 
      angled endoscope. CONCLUSIONS: LETEA through the pterygopalatine fossa is
      minimally invasive and provides direct access to the temporal pole and medial
      part of the temporal lobe. This approach may reduce risk of neurologic deficit
      and help to avoid cosmetic defects in the frontotemporal region associated with
      injury to temporal muscle and facial nerve injury as can occur during
      transcranial approaches. Disadvantages that limit application of LETEA include
      risk of cerebrospinal fluid leak and skills needed for manipulation in a narrow
      and deep surgical field with angled 30 degrees  and 45 degrees  endoscopes.

PMID- 28434958
TI  - Microsurgical Resection After Failed Gamma Knife Radiosurgery of Papillary Tumor
      of the Pineal Gland.

PMID- 28434959
TI  - Analysis of 137 Patients Who Underwent Endoscopic Transsphenoidal Pituitary
      Adenoma Resection Under High-Field Intraoperative Magnetic Resonance Imaging
      Navigation.
AB  - BACKGROUND: Pure endoscopic resection has become the most popular surgical
      approach for pituitary adenoma. Intraoperative magnetic resonance imaging (iMRI)
      systems have been in use for endoscopic resection of pituitary adenomas. This
      study aimed to evaluate the effectiveness of iMRI and neuroimaging navigation
      techniques during endoscopic endonasal transsphenoidal surgery of pituitary
      adenomas. METHODS: Data from 137 patients who underwent resection of endoscopic
      pituitary adenoma under 1.5T iMRI navigation were collected and analyzed.
      RESULTS: Of patients, 92 underwent complete resection and 45 had residual tumor
      on real-time iMRI. Twenty-three patients underwent further surgery, and total
      resection was achieved in 19. Extent of total resection increased from 67.15% to
      81.02%. iMRI revealed 3 patients with bleeding in the surgical area, which was
      successfully treated during the surgery. Review images obtained 3 months after
      surgery showed 26 patients with residual tumor; 14 patients had the same volume
      as intraoperatively, and 12 patients had a volume less than that observed
      intraoperatively. Residual tumor volume in the suprasellar region was less than
      that seen intraoperatively in 11 of 15 (73.3%) patients. CONCLUSIONS: The use of
      iMRI and neuronavigation not only leads to a higher rate of tumor resection but
      also helps in detecting and removing hematomas in the surgical area. Follow-up
      examinations of extent of residual tumor at 3 months postoperatively were
      consistent with intraoperative results. Residual tumor volume in the suprasellar
      region was usually less than that observed intraoperatively.

PMID- 28434961
TI  - Cranioplasty Infection and Resorption Are Associated with the Presence of a
      Ventriculoperitoneal Shunt: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Following decompressive craniectomy, hydrocephalus is a common
      complication often necessitating placement of a ventriculoperitoneal shunt (VPS).
      Complications in the presence of a VPS have been reported, but a clear
      association has not been established. METHODS: PRISMA guidelines were used to
      perform a literature search using PubMed to identify articles that published the
      complication rates associated with staged or simultaneous cranioplasty and VPS
      placement. From these event rates, odds ratios (ORs) with 95% confidence
      intervals (CIs) of complications were calculated. Data were pooled using the
      Mantel-Haenszel method. The Oxford Center for Evidence-Based Medicine guidelines
      were used to assess the quality of individual articles and studies. The Newcastle
      Ottawa Scale was used to assess the risk of bias in studies. RESULTS: Of the 30
      papers reviewed for complications in the presence and absence of a VPS, 7
      studies, with a total of 1635 patients, were eligible for meta-analysis. Overall
      rates of complications (n = 1635; OR, 9.75; 95% CI, 4.8-20.1), infection (OR,
      4.9; 95% CI, 2.2-10.7), and bone resorption (OR, 10.6; 95% CI, 4.9-23.0) were
      increased when a VPS was placed at the time of cranioplasty. Simultaneous
      procedures were associated with increased complication rates (n = 283; OR, 4.3;
      95% CI, 2.3-8.2) compared with staged procedures. CONCLUSIONS: Cranioplasty in
      the presence of a VPS is associated with a higher rate of overall complications,
      including infection and bone resorption. Performing cranioplasty and VPS
      placement in the same operation is associated with an increased rate of
      complications compared with staged procedures. Surgeons should consider staging
      these procedures when possible and counsel patients about these risks.

PMID- 28434960
TI  - Solitary Cysticercal Cyst Inside the Blake's Pouch Remnant of Mega Cisterna Magna
      with Associated Aqueductal Stenosis: Clinical and Management Implications.
AB  - BACKGROUND: Intraventricular and subarachnoid forms represent the relatively
      complex, albeit uncommon, manifestations of central nervous system involvement by
      cysticercal cysts. Cysticercal encystation inside the Blake's pouch remnant of
      mega cisterna magna (MCM) remains an extremely rare clinical scenario that, to
      the best of our knowledge, has not been reported previously. CASE PRESENTATION: A
      12-year-old boy presented with acute worsening and subsequent spontaneous
      resolution of his compensated hydrocephalus. Neuroimaging revealed features
      consistent with a MCM with septum inside, indicating remnants of the embryologic
      fourth ventricular diverticulum, the Blake's pouch. It also revealed a free
      floating intact cysticercal cyst inside the MCM limited by the septum with
      aqueductal stenosis. The spontaneous clinicoradiologic resolution of
      hydrocephalus raised the possibility of ball valve obstruction of the
      cerebrospinal fluid outflow, i.e., Bruns syndrome. We successfully treated this
      patient with endoscopic extraction of the viable cysticercal cyst through a
      suboccipital burrhole. CONCLUSIONS: The clinical scenario presented here has not
      been described previously. Endoscopic cyst removal in such a situation is an
      effective and low-risk procedure that obviates the further need for
      antihelminthic medications.

PMID- 28434962
TI  - Outcome of Biomedical Glue Sling Technique in Microvascular Decompression for
      Hemifacial Spasm Involving the Vertebral Artery.
AB  - BACKGROUND: Microvascular decompression (MVD) is the most useful treatment for
      hemifacial spasm (HFS). In cases of vertebral artery (VA) compression of the
      facial nerve, MVD is often difficult. In this study, we compared the outcome of
      the biomedical glue sling technique with the traditional technique in MVD for HFS
      involving the VA. METHODS: A retrospective study of patients with HFS treated by
      MVD was conducted between January 2013 and December 2015. A total of 327 patients
      with VA-associated HFS underwent their first MVD at our institution. Among them,
      the traditional technique was performed in 153 patients and the biomedical glue
      sling technique was performed in 174 patients. We measured effectiveness at 1
      day, 7 days, 1 month, 3 months, and 1 year after MVD surgery. RESULTS: In the
      traditional technique group, the effective rates of MVD were 89.54%, 88.89%,
      89.40%, 88.44%, and 86.71%, and the incidence rates of complication were 5.23%,
      4.58%, 3.97%, 2.72%, and 0.70%. In the biomedical glue sling technique group, the
      effective rates of operation were 96.55%, 96.55%, 97.66%, 95.86%, and 95.76% (P <
      0.05), and the incidence rates of complication were 8.62%, 8.62%, 7.60%, 4.73%,
      and 2.42% (P > 0.05). CONCLUSION: When the HFS were associated with the VA, the
      effective rate of biomedical glue sling technique of MVD was higher than the
      traditional technique, and there was no statistical difference between the 2
      groups about the incidence of complication.

PMID- 28434963
TI  - Recurrence Pattern Analysis of Primary Glioblastoma.
AB  - BACKGROUND: Typical recurrence of glioblastoma occurs locally, usually within 2
      cm from the original lesion. With improvement of surgical techniques, more
      aggressive surgical strategies have become feasible, resulting in a significantly
      increased rate of complete resection. We investigated whether these improvements
      are also reflected by tumor recurrence pattern. METHODS: Inclusion criteria were
      first diagnosis of glioblastoma with standard adjuvant radiochemotherapy and
      histologically proven tumor recurrence. Patients were divided according to
      recurrence pattern: local recurrence, distant recurrence, or both recurrence
      patterns. Data were correlated with extent of resection, molecular tumor
      configuration, clinical status, and survival data. RESULTS: This single-center
      retrospective study included 97 patients with glioblastoma treated between 2007
      and 2014. Local, distant, and combined tumor recurrence patterns were observed in
      77 (79.3%), 10 (10.3%), and 10 patients (10.3%). Median progression-free survival
      of all patients was 8 months; median overall survival was 20 months. Median
      progression-free survival was 7 months for patients with local recurrence, 13
      months for patients with distant recurrence, and 9 months for patients with both
      recurrence patterns (P = 0.646). Median overall survival in the 3 groups was 21
      months, 20 months, and 14 months (P = 0.098). No correlation between
      methylguanine-deoxyribonucleic acid methyltransferase methylation status and
      recurrence pattern was observed. CONCLUSIONS: Despite complete resection of
      contrast-enhancing tumor, most recurrences occurred locally. Patients with
      distant tumor recurrence demonstrated increased progression-free survival.
      Therefore, to gain local control, we may need to shift toward a more aggressive
      supramarginal resection, using extensive intraoperative monitoring to avoid
      permanent deficits.

PMID- 28434964
TI  - Reconstruction of Cranial Vault Defect with Polyetheretherketone Implants.
AB  - OBJECT: Reconstruction of a cranial vault defect is a frequent challenge in
      neurosurgery. Polyetheretherketone (PEEK) is used in many types of prostheses and
      has been employed for 10 years in our institution (University Hospital of
      Toulouse, France). The objectives of this study are to describe the benefits and
      drawbacks of reconstructing the cranial vault defect with a PEEK prosthesis.
      METHODS: Clinical data of the 37 patients who received a reconstruction with a
      custom-made PEEK prosthesis from 2007-2015 were retrospectively analysed.
      Operative technique, postoperative complications, and patient's satisfaction with
      the aesthetic result-on a scale ranging from 1 (very dissatisfied) to 5 (very
      satisfied)-were studied. RESULTS: Average follow-up was 4.3 years (from 2 months
      9 years). The placement of the prosthesis was performed 195 days on average (from
      0-1051 days, standard deviation 258 days) after the initial bone flap removal.
      One infection (2.7%), which required the removal of the prosthesis, was
      described. Six patients (16%) were reoperated by the maxillofacial surgery team
      to treat a lack of temporal projection related to muscle atrophy, using a fat
      cell autograft taken from the abdominal region. Overall, 30 patients (81%)
      answered the question about their aesthetic satisfaction, with good results on
      the satisfaction scale (average 4.5; from 3-5). CONCLUSION: The use of a PEEK
      prosthesis in cranial vault defect reconstruction is a reliable technique with a
      high patient satisfaction rate and few complications. Corrections of the temporal
      muscle atrophy by fat grafting may be performed in addition, without increasing
      the rate of complications.

PMID- 28434965
TI  - Trochlear Schwannoma Presenting with Isolated Trigeminal Neuralgia.
AB  - BACKGROUND: Schwannomas arising from the cranial nerves controlling extraocular
      eye movements are very rare and usually present with some degree of diplopia.
      CASE PRESENTATION: We report a 50-year-old woman who presented with isolated left
      sided trigeminal neuralgia of 6 months' duration. Imaging demonstrated a
      homogeneously enhancing mass in the left ambient cistern, and the patient was
      brought to the operating room for resection. A retrosigmoid approach was used,
      and the mass was directly visualized arising from the trochlear nerve and
      compressing the dorsal root entry zone of the trigeminal nerve. A gross total
      resection of the mass was achieved, and microvascular decompression of the
      trigeminal nerve was performed. The tumor was pathologically confirmed as a
      schwannoma. At 3-month follow-up, the patient's facial pain was resolved, and her
      extraocular eye movements were intact. CONCLUSIONS: A total of 32 pathology
      confirmed cases of trochlear schwannoma have been previously reported in the
      English-language literature. Most of these tumors arose from the cisternal
      segment of the nerve, and most patients presented with frank trochlear nerve
      palsy on exam. We report the first case of trochlear schwannoma presenting with
      isolated trigeminal neuralgia.

PMID- 28434966
TI  - Diagnostic Biopsy of a Motor Branch of the Superficial Peroneal Nerve to the
      Peroneus Longus: A Convenient Alternative for Motor Nerve Biopsy.
AB  - BACKGROUND: Motor nerve biopsy is performed to supplement clinical, serologic,
      and imaging data in the workup of neuropathies of unknown origin, especially when
      motor neuron disease is suspected. METHODS: We describe a surgical technique for
      biopsy of a motor branch of the superficial peroneal nerve innervating the
      peroneus longus muscle. RESULTS: Three patients presented with weakness
      concerning for motor neuropathy and underwent biopsy of a motor branch of the
      superficial peroneal nerve innervating the peroneus longus muscle. The surgical
      technique is described in detail. Biopsied tissue was sufficient for pathologic
      diagnosis. No patient suffered postsurgical sensory or motor deficits related to
      the procedure. No patient suffered postsurgical complications. CONCLUSIONS:
      Biopsy of the motor branch of the superficial peroneal nerve to the peroneus
      longus is a safe and effective alternative for motor nerve biopsy and can be
      easily combined with peroneus longus muscle biopsy.

PMID- 28434967
TI  - Cysteinylated transthyretin as a discriminator of cardiovascular risk in patients
      with diabetes mellitus.
AB  - BACKGROUND: The cysteine residue on transthyretin (TTR) is susceptible to be
      oxidized, and serum cysteinylated TTR (Cys-TTR) level is thought to reflect
      oxidative stress. The purpose of this study was to elucidate the relationship
      between Cys-TTR and arterial stiffness, a known predictor of cardiovascular
      disease, in patients with type 2 diabetes. METHODS: The subjects were 105 male
      outpatients with type 2 diabetes. Arterial stiffness was evaluated by measuring
      cardio-ankle vascular index (CAVI). The relationship between CAVI and ratio of
      Cys-TTR to total TTR (Cys-TTR ratio) was analyzed. RESULTS: Cys-TTR ratio was
      significantly correlated with CAVI (Pearson's correlation coefficient: 0.316,
      p<0.01), and CAVI was significantly higher in the 3rd tertile group for Cys-TTR
      ratio than in its 1st tertile group. These relationships were also significant
      after adjusting for age, smoking, alcohol drinking, body mass index, mean
      arterial pressure, hemoglobin A1c, LDL cholesterol-to-HDL cholesterol ratio and
      eGFR. Prevalence of high CAVI (>=10.0) was significantly higher in the 3rd
      tertile for Cys-TTR ratio than in its 1st tertile and tended to be higher with an
      increase in tertile (28.6% in the 1st tertile, 42.9% in the 2nd tertile and 60.0%
      in the 3rd tertile). Odds ratio (OR) for high CAVI of the 3rd vs. 1st tertile
      groups for Cys-TTR ratio was significantly higher than the reference level of
      1.00 both before and after adjustment for the above cardiovascular risk factors
      (crude OR, 3.75 [1.38-10.17]; adjusted OR, 5.09 [1.39-18.64]). CONCLUSIONS: Cys
      TTR ratio is associated with arterial stiffness in patients with diabetes and is
      proposed as a new discriminator of cardiovascular risk.

PMID- 28434968
TI  - Cardiac contractility: Correction strategies applied to telemetry data from a
      HESI-sponsored consortium.
AB  - INTRODUCTION: QT has a long history of heart rate (HR) correction but limited
      investigations have been undertaken to assess the impact of cardiovascular
      parameters on left ventricular (LV) contractility in drug safety testing. Cardiac
      contractility is affected by preload (Cyon-Frank-Starling law), afterload (Anrep
      effect) and HR (Bowditch effect). We evaluated multi-parameter correction methods
      to help with dP/dtmax interpretation. METHODOLOGY: Modeling was undertaken using
      data from dogs in single or double 4*4 Latin square studies. Correction models
      (16 fitting formulas*2 modeling approaches (universal and individualized)*2
      correction approaches (linear or proportional)) were evaluated. 3D/2D cloud
      analysis of the beat-to-beat data for the control, pimobendan, and either
      itraconazole or atenolol groups were used to evaluate correlations between
      parameters and derive an optimal correction method. RESULTS: Cardiac
      contractility (i.e., dP/dtmax) was best correlated to HR and systolic LV pressure
      with a correlation coefficient of 0.8. In decreasing order, dP/dtmin, mean
      arterial blood pressure (BP), systolic BP, diastolic BP, arterial pulse pressure
      and LV end diastolic pressure (LVEDP) showed a reduced correlation to dP/dtmax.
      Subject-specific models improved the correction by up to 14% when compared to
      universal correction models. The non-linear correction model was superior to the
      linear model. DISCUSSION: Results suggest that the optimal correction formula for
      dP/dtmax would be subject-specific, non-linear and would include HR and LV
      systolic pressure. Correcting contractility for HR and systolic LV pressure may
      enhance data interpretation in non-clinical drug safety assessments. Similar
      correction methods could be evaluated for other species used in safety
      pharmacology.

PMID- 28434969
TI  - Translational science approach for assessment of cardiovascular effects and
      proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron.
AB  - INTRODUCTION: Translational assessment of cardiac safety parameters is a
      challenge in clinical development of beta-3 adrenoceptor agonists. The
      preclinical tools are presented that were used for assessing human safety for
      mirabegron. METHODS: Studies were performed on electrical conductance at ion
      channels responsible for cardiac repolarization (IKr, IKs, Ito, INa, and ICa,L),
      on QT-interval, subendocardial APD90, Tpeak-end interval, and arrhythmia's in
      ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and
      QTc) in conscious dogs. RESULTS: In conscious dogs, mirabegron (0.01-10mg/kg,
      p.o.) dose-dependently increased HR, reduced SBP but DBP was unchanged.
      Propranolol blocked the decrease in SBP and attenuated HR increase at 100mg/kg
      mirabegron. Mirabegron, at 30, 60, or 100mg/kg, p.o., had no significant effect
      on the QTc interval. In paced dog ventricular wedge, neither mirabegron nor
      metabolites M5, M11, M12, M14, and M16 prolonged QT, altered transmural
      dispersion of repolarization, induced premature ventricular contractions, or
      induced ventricular tachycardia. Mirabegron nor its metabolites inhibited IKr,
      IKs, Ito INa, or ICa,L at clinically relevant concentrations. DISCUSSION: Up to
      exposure levels well exceeding human clinical exposure no discernible effects on
      ion channel conductance or on arrhythmogenic parameters in ventricular wedge
      resulted for mirabegron, or its main metabolites, confirming human cardiac safety
      findings. In vivo, dose-related increases in HR with effects markedly higher than
      seen clinically, was mediated in part by cross-activation of beta-1
      adrenoceptors. This non-clinical cardiac safety test program therefore proved
      predictive for human cardiac safety for mirabegron.

PMID- 28434971
TI  - Prevalence and genetic characterization of Toxoplasma gondii in badgers (Melogale
      moschata) in southern China by PCR-RFLP.
AB  - Toxoplasma gondii is an obligate intracellular apicomplexan parasite which is
      able to infect almost all warm-blooded animals. There is no information about the
      prevalence and genetic characterization of T. gondii in badgers (Melogale
      moschata) in China. Here, a total of 367 badgers were captured from different
      cities in Jiangxi province, Southern China. Genomic DNA was extracted from brain
      tissues of each badgers, and 57 (15.45%) of them were positive for T. gondii by
      semi-nested PCR of the B1 gene. The positive DNA samples were typed at 11 genetic
      markers, including 10 nuclear loci (SAG1, 5'-SAG2 and 3'-SAG2, alternative SAG2,
      SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1) and an apicoplast locus (Apico), with
      multilocus polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) technology. Among them, 4 were completely typed at all loci, and 2 was
      genotyped for 9 loci, showing that they belong to ToxoDB#9. This is the first
      report of prevalence and genetic characterization of T. gondii isolates from
      badgers in China, which contributes to broader understanding of population
      structure of T. gondii in China. It is important for the prevention and control
      of T. gondii infection in wild animals.

PMID- 28434970
TI  - Transfer of C-terminal residues of human apolipoprotein A-I to insect
      apolipophorin III creates a two-domain chimeric protein with enhanced lipid
      binding activity.
AB  - Apolipophorin III (apoLp-III) is an insect apolipoprotein (18kDa) that comprises
      a single five-helix bundle domain. In contrast, human apolipoprotein A-I (apoA-I)
      is a 28kDa two-domain protein: an alpha-helical N-terminal domain (residues 1
      189) and a less structured C-terminal domain (residues 190-243). To better
      understand the apolipoprotein domain organization, a novel chimeric protein was
      engineered by attaching residues 179 to 243 of apoA-I to the C-terminal end of
      apoLp-III. The apoLp-III/apoA-I chimera was successfully expressed and purified
      in E. coli. Western blot analysis and mass spectrometry confirmed the presence of
      the C-terminal domain of apoA-I within the chimera. While parent apoLp-III did
      not self-associate, the chimera formed oligomers similar to apoA-I. The chimera
      displayed a lower alpha-helical content, but the stability remained similar
      compared to apoLp-III, consistent with the addition of a less structured domain.
      The chimera was able to solubilize phospholipid vesicles at a significantly
      higher rate compared to apoLp-III, approaching that of apoA-I. The chimera was
      more effective in protecting phospholipase C-treated low density lipoprotein from
      aggregation compared to apoLp-III. In addition, binding interaction of the
      chimera with phosphatidylglycerol vesicles and lipopolysaccharides was
      considerably improved compared to apoLp-III. Thus, addition of the C-terminal
      domain of apoA-I to apoLp-III created a two-domain protein, with self
      association, lipid and lipopolysaccharide binding properties similar to apoA-I.
      The apoA-I like behavior of the chimera indicate that these properties are
      independent from residues residing in the N-terminal domain of apoA-I, and that
      they can be transferred from apoA-I to apoLp-III.

PMID- 28434972
TI  - One bacillus to rule them all? - Investigating broad range host adaptation in
      Mycobacterium bovis.

PMID- 28434973
TI  - Long-term oral kinetin does not protect against alpha-synuclein-induced
      neurodegeneration in rodent models of Parkinson's disease.
AB  - Mutations in the mitochondrial kinase PTEN-induced putative kinase 1 (PINK1)
      cause Parkinson's disease (PD), likely by disrupting PINK1's kinase activity.
      Although the mechanism(s) underlying how this loss of activity causes
      degeneration remains unclear, increasing PINK1 activity may therapeutically
      benefit some forms of PD. However, we must first learn whether restoring PINK1
      function prevents degeneration in patients harboring PINK1 mutations, or whether
      boosting PINK1 function can offer protection in more common causes of PD. To test
      these hypotheses in preclinical rodent models of PD, we used kinetin
      triphosphate, a small-molecule that activates both wild-type and mutant forms of
      PINK1, which affects mitochondrial function and protects neural cells in culture.
      We chronically fed kinetin, the precursor of kinetin triphosphate, to PINK1-null
      rats in which PINK1 was reintroduced into their midbrain, and also to rodent
      models overexpressing alpha-synuclein. The highest tolerated dose of oral kinetin
      increased brain levels of kinetin for up to 6 months, without adversely affecting
      the survival of nigrostriatal dopamine neurons. However, there was no
      degeneration of midbrain dopamine neurons lacking PINK1, which precluded an
      assessment of neuroprotection and raised questions about the robustness of the
      PINK1 KO rat model of PD. In two rodent models of alpha-synuclein-induced
      toxicity, boosting PINK1 activity with oral kinetin provided no protective
      effects. Our results suggest that oral kinetin is unlikely to protect against
      alpha-synuclein toxicity, and thus fail to provide evidence that kinetin will
      protect in sporadic models of PD. Kinetin may protect in cases of PINK1
      deficiency, but this possibility requires a more robust PINK1 KO model that can
      be validated by proof-of-principle genetic correction in adult animals.

PMID- 28434974
TI  - Proteomic approach to detect changes in hippocampal protein levels in an animal
      model of type 2 diabetes.
AB  - In our previous study, we demonstrated that type 2 diabetes affects blood-brain
      barrier integrity and ultrastructural morphology in Zucker diabetic fatty (ZDF)
      rats at 40 weeks of age. In the present study, we investigated the possible
      candidates for diabetes-related proteins in the hippocampus of ZDF rats and their
      control littermates (Zucker lean control, ZLC), by using two-dimensional
      fluorescence difference gel electrophoresis (2D-DIGE) followed by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF).
      Approximately 2756 protein spots were detected by 2D-DIGE, and an increase or
      decrease of more than 1.4-fold was observed for 13 proteins in the hippocampal
      homogenates of ZDF rats relative to those of ZLC rats. Among these proteins, we
      found four proteins whose levels were significantly lower in the hippocampi of
      ZDF rats than in those of ZLC rats: glial fibrillary acidic protein (GFAP),
      apolipoprotein A-I preprotein (apoAI-P), myelin basic protein (MBP), and
      rCG39881, isoform CRA_a. Among these proteins, apoAI-P protein levels were
      decreased most prominently in ZDF rats than in ZLC rats, based on Western blot
      analysis. In addition, immunohistochemical and Western blot studies demonstrated
      that MBP, not GFAP, immunoreactivity and protein levels were significantly
      decreased in the hippocampus of ZDF rats compared to ZLC rats. In addition,
      ultrastructural analysis showed that ZDF rats showed myelin degeneration and
      disarrangement in the hippocampal tissue. These results suggest that chronic type
      2 diabetes affects hippocampal function via reduction of MBP and apoAI-P levels
      as well as disarrangement of myelin.

PMID- 28434975
TI  - Protection of PC12 cells from cocaine-induced cell death by inhibiting
      mitochondrial permeability transition.
AB  - Cocaine abuse induces brain injury and neurodegeneration by a mechanism that has
      not yet been fully elucidated. Mitochondria play a key role in cell death
      processes, notably through the opening of the permeability transition pore (PTP).
      In this work, we examined the involvement of the PTP in cocaine-induced toxicity
      in PC12 cell lines. We used two different PTP inhibitors -i.e. cyclosporin A
      (CsA) and metformin-to assess their ability to counteract the cocaine induced
      effects. We first observed that a 48 h exposure to cocaine strongly sensitized
      cells to calcium overload, as measured by the calcium retention capacity. CsA and
      metformin significantly decreased the cocaine-induced PTP opening sensitization.
      We next showed by confocal microscopy that cocaine induced a permanent PTP
      opening in intact living cells, a phenomenon characterized by the collapse of the
      mitochondrial membrane potential and the relocation of the NAD(P)H from the
      mitochondrial matrix to the cytosol. As expected, a cocaine-induced PTP opening
      was prevented by PTP inhibitors. Finally, a flow cytometry analysis revealed that
      cocaine induced cell death while CsA and metformin promoted cell survival. Our
      results demonstrate that cocaine induces PC12 cell death through a mechanism
      involving permanent PTP opening.

PMID- 28434976
TI  - Compartmentalized microfluidic perfusion system to culture human induced
      pluripotent stem cell aggregates.
AB  - Microfluidic perfusion systems enable small-volume cell cultures under precisely
      controlled microenvironments, and are typically developed for cell-based high
      throughput screening. However, most such systems are designed to manipulate
      dissociated single cells, not cell aggregates, and are thus unsuitable to induce
      differentiation in human induced pluripotent stem cells (hiPSCs), which is
      conventionally achieved by using cell aggregates to increase cell-cell
      interactions. We have now developed a compartmentalized microfluidic perfusion
      system with large flow channels to load, culture, and observe cell aggregates.
      Homogeneously sized cell aggregates to be loaded into the device were prepared by
      shredding flat hiPSC colonies into squares. These aggregates were then seeded
      into microchambers coated with fibronectin and bovine serum albumin (BSA) to
      establish adherent and floating cultures, respectively, both of which are
      frequently used to differentiate hiPSCs. However, the number of aggregates loaded
      in fibronectin-coated microchambers was much lower than in BSA-coated
      microchambers, suggesting that fibronectin traps cell aggregates before they
      reach the chambers. Accordingly, hiPSCs that reached the microchambers
      subsequently adhered. In contrast, BSA-coated microchambers did not allow cell
      aggregates to adhere, but were sufficiently deep to prevent cell aggregates from
      flowing out during perfusion of media. Immunostaining for markers of
      undifferentiated cells showed that cultures on both fibronectin- and BSA-coated
      microchambers were successfully established. Notably, we found that floating
      aggregates eventually adhered to surfaces coated with BSA upon differentiation,
      and that differentiation depends on the initial size of aggregates. Collectively,
      these results suggest that the microfluidic system is suitable for manipulating
      hiPSC aggregates in compartmentalized microchambers.

PMID- 28434977
TI  - Starch-fueled microbial fuel cells by two-step and parallel fermentation using
      Shewanella oneidensis MR-1 and Streptococcus bovis 148.
AB  - Shewanella oneidensis MR-1 generates electricity from lactic acid, but cannot
      utilize starch. On the other hand, Streptococcus bovis 148 metabolizes starch and
      produces lactic acid. Therefore, two methods were trialed for starch-fueled
      microbial fuel cell (MFC) in this study. In electric generation by two-step
      fermentation (EGT) method, starch was first converted to lactic acid by S. bovis
      148. The S. bovis 148 were then removed by centrifugation, and the fermented
      broth was preserved for electricity generation by S. oneidensis MR-1. Another
      method was electric generation by parallel fermentation (EGP) method. In this
      method, the cultivation and subsequent fermentation processes of S. bovis 148 and
      S. oneidensis MR-1 were performed simultaneously. After 1, 2, and 3 terms (5-day
      intervals) of S. oneidensis MR-1 in the EGT fermented broth of S. bovis 148, the
      maximum currents at each term were 1.8, 2.4, and 2.8 mA, and the maximum current
      densities at each term were 41.0, 43.6, and 49.9 mW/m2, respectively. In the EGP
      method, starch was also converted into lactic acid with electricity generation.
      The maximum current density was 140-200 mA/m2, and the maximum power density of
      this method was 12.1 mW/m2.

PMID- 28434978
TI  - Calycosin promotes lifespan in Caenorhabditis elegans through insulin signaling
      pathway via daf-16, age-1 and daf-2.
AB  - The naturally occurring calycosin is a known antioxidant that prevents redox
      imbalance in organisms. However, calycosin's effect on lifespan and its
      physiological molecular mechanisms are not yet well understood. In this study, we
      demonstrated that calycosin could prolong the lifespan of Caenorhabditis elegans,
      and that such extension was associated with its antioxidant capability as well as
      its ability to enhance stress resistance and reduce ROS (reactive oxygen species)
      accumulation. To explore mechanisms of this longevity effect, we assessed the
      impact of calycosin on lifespans of insulin-signaling impaired worms: daf-2, age
      1, and daf-16 mutants. We found that calycosin did not alter the lifespan of all
      three mutants, thereby suggesting that calycosin requires insulin signaling to
      promote lifespan extension. On the other hand, we observed that calycosin could
      enhance the nuclear translocation of the core transcription factor DAF-16/FoXO
      instead of the conserved stress-responsive transcription factor SKN-1/Nrf-2. This
      observation is consistent with the understanding that the nuclear localized DAF
      16 up-regulates its downstream targets sod-3, ctl-1, and hsp-16.2. Lastly, it is
      also noteworthy that the longevity effect of calycosin is likely not associated
      with the calorie restriction mechanism. Collectively, our results strongly
      suggest that calycosin could function as an antioxidant to extend the lifespan of
      C. elegans by enhancing nucleus translocation of DAF-16 through the insulin
      signaling pathway.

PMID- 28434979
TI  - Synergistic effects of BMP-2, BMP-6 or BMP-7 with human plasma fibronectin onto
      hydroxyapatite coatings: A comparative study.
AB  - : Design of new osteoinductive biomaterials to reproduce an optimized
      physiological environment capable of recruiting stem cells and instructing their
      fate towards the osteoblastic lineage has become a priority in orthopaedic
      surgery. This work aims at evaluating the bioactivity of BMP combined with human
      plasma fibronectin (FN/BMP) delivered in solution or coated onto titanium
      hydroxyapatite (TiHA) surfaces. Herein, we focus on the comparison of in vitro
      osteogenic efficacy in mouse C2C12 pre-osteoblasts of three BMP members, namely:
      BMP-2, BMP-6 and BMP-7. In parallel, we evaluated the molecular binding strength
      between each BMP with FN using the Surface Plasmon Resonance (SPR) technology.
      The affinity of BMPs for FN was found totally different and dependent on BMP
      type. Indeed, the combination of FN with BMP-2 on TiHA surfaces potentiates the
      burst of gene-mediated osteogenic induction, while it prolongs the osteogenic
      activity of BMP-6 and surprisingly annihilates the BMP-7 one. These results
      correlate with FN/BMP affinity for TiHA, since BMP-6>BMP-2>BMP-7. In addition, by
      analyzing the osteogenic activity in the peri-implant environment, we showed that
      osteoinductive paracrine effects were significantly decreased upon (FN/BMP-6), as
      opposed to (FN/BMP-2) coatings. Altogether, our results support the use of FN/BMP
      6 to develop a biomimetic microenvironment capable to induce osteogenic activity
      under physiological conditions, with minimum paracrine signalization. STATEMENT
      OF SIGNIFICANCE: The originality of our paper relies on the first direct
      comparison of the in vitro osteogenic potential of three osteogenic BMPs (BMP-2, 
      6 and -7) combined with native human plasma fibronectin delivered in solution or
      coated by laser transfer onto titanium hydroxyapatite surfaces. We confirm that
      BMP association with fibronectin enhances the osteogenic activity of BMP-2, -6
      and -7, but with essential discrepancies, depending on the BMP member, and in
      agreement with the affinity of BMPs for fibronectin. Moreover, we bring elements
      to explain the origin of the BMP-2 medical life-threatening side-effects by
      analyzing in vitro paracrine effects. Finally, this work supports the alternative
      use of FN/BMP-6 to induce osteogenic activity under physiological conditions,
      with minimum side effects.

PMID- 28434980
TI  - Thaw-and-use target cells pre-labeled with calcein AM for antibody-dependent cell
      mediated cytotoxicity assays.
AB  - In vitro antibody-dependent cell-mediated cytotoxicity (ADCC) assays are
      routinely performed to support the research and development of therapeutic
      antibodies. In ADCC assays, target cells bound by the antibodies are lysed by
      activated effector cells following interactions between the Fc region of the
      bound antibody and Fcgamma receptors on effector cells. Target cell lysis is
      typically measured by quantification of released endogenous enzymes, e.g.,
      lactate dehydrogenase, or measurement of released exogenous labels, e.g., 51Cr,
      europium or calcein. ADCC assays based on the detection of exogenous labels
      released from lysed target cells generally show higher sensitivity and require
      shorter incubation times. However, target cells are usually labeled immediately
      prior to assay, which inadvertently introduces additional assay variations due to
      differences in target cell conditions and labeling/handling processes. In this
      report, we describe the use of thaw-and-use pre-labeled target cells for ADCC
      assays. Thaw-and-use target cells in our experiments were pre-labeled with the
      fluorescent dye calcein AM, cryopreserved in single-use aliquots and used
      directly in assays after thawing. Upon thaw, the pre-labeled cells displayed
      viability and label retention comparable to freshly labeled cells, responded to
      ADCC mediated by both peripheral blood mononuclear cells and engineered natural
      killer cells, performed stably for at least 3 years and provided favorable
      precision and accuracy to ADCC assays. Implementation of thaw-and-use pre-labeled
      target cells in ADCC assays can help to alleviate both cell culture and dye
      labeling derived variability, increase the flexibility of assay scheduling and
      improve assay consistency and robustness.

PMID- 28434981
TI  - Protein transport inhibitors downregulate the expression of LAG-3 on regulatory T
      cells.
AB  - Modern immunologic studies demand increasing complexity because of a need to
      improve our understanding of the relationship between a cell's phenotype and its
      function. Regulatory T cells (Tregs) have been defined by a narrow set of
      phenotypic markers, however their actual functional capacity has not been
      determined at the single-cell level. Although the lymphocyte activation gene 3
      (LAG-3; CD223) is a key marker for the identification of exhausted T cells, it
      may be useful also in resolving Treg subpopulations by indicating distinct
      functional breadths. Here we define the experimental conditions necessary for the
      optimal detection by flow cytometry of LAG-3 expression on activated Tregs. We
      stimulated human PBMCs with either PMA/ionomycin or Staphylococcal Enterotoxin B
      (SEB) and analyzed CD4+CD25+FoxP3+ Tregs for LAG-3 expression in concert with
      other Treg phenotypic markers. We prescribe a 24-hour stimulation period for the
      optimal detection of LAG-3 on Tregs. Furthermore, we determine LAG-3 protein
      expression on Tregs is compromised when the cells are treated with brefeldin A
      (BFA) and monensin. Therefore, the simultaneous assessment of Treg phenotype and
      function is complicated by the use of protein transport inhibitors.

PMID- 28434982
TI  - Novel monoclonal antibodies against Stx1d and 1e and their use for improving
      immunoassays.
AB  - Shiga toxins (Stxs) are major causative agents for bloody diarrhea and hemolytic
      uremic syndrome, a life-threatening disease in humans. No effective treatment is
      available. Early detection of Stxs in clinical samples is critical for disease
      management. As bacteria evolve, new Stxs are produced; therefore, methods used to
      identify them need to be improved as well. In this study, new monoclonal
      antibodies (mAbs) against Stx1d and 1e were developed and used to improve a
      commercial Stx1 kit. Incorporation of the new mAbs into the Abraxis Stx1 kit not
      only increased the assay sensitivity to Stx1d, but the assay was conferred the
      ability to detect Stx1e, a newly identified subtype of Stx1 produced by an
      atypical Stx-producing bacterial strain, Enterobacter cloacae M12X01451, isolated
      from a clinical specimen. This toxin was not detectable using existing commercial
      kits. The signal to noise ratio (s/n) of the new assay was increased 3-fold for
      Stx1d, and 44-fold for Stx1e at toxin concentration of 10ng/mL. The limit of
      detection (LOD) was 10pg/mL for Stx1a, and 100pg/mL for Stx1c, 1d and 1e. When
      used for bacterial strains, the sensitivity of the new assay was improved 2.5- to
      60-fold depending on subtypes produced. In summary, high affinity mAbs against
      Stx1d and 1e were developed and incorporation of these mAbs into the Stx1 kit
      significantly enhanced the assay sensitivity and broadened the subtype
      specificity. This improvement should be useful for reducing product recalls and
      disease mistreatment due to failures of detecting less common but clinically
      important subtypes of Stxs.

PMID- 28434983
TI  - Future perspective of butter flavorings-related occupational lung disease.

PMID- 28434986
TI  - The emerging landscape of scientific publishing.
AB  - We present emerging models of publishing which have grown from the phenomenon of
      open access, the changing role of peer review in the scientific process and the
      new position of the impact factor. We juxtapose the new models of paid review,
      eponymous review, no review, post publication review and light review with the
      classic model which has dominated for a century, detailing advantages, problems
      and examples of each model to provide a comprehensive overview of the changing
      landscape of scientific publishing.

PMID- 28434985
TI  - Performance specifications in extra-analytical phase of laboratory testing:
      Sample handling and transportation.

PMID- 28434984
TI  - The Nonpalpable Testis: A Narrative Review.
AB  - PURPOSE: While the nonpalpable testis represents a small portion of all
      cryptorchid testes, it remains a clinical challenge for pediatric urologists.
      Controversy exists surrounding the best evaluation and management of this entity.
      In this review we update what is known about the nonpalpable testis, including
      the etiology, preoperative evaluation and best surgical management as well as
      novel techniques and ongoing controversies. MATERIALS AND METHODS: We searched
      PubMed(r) and MEDLINE(r) from January 2000 to January 2017 using relevant key
      terms. Of 367 articles 115 were considered for inclusion based on a priori
      design. Using a narrative review format, an update on the evaluation and
      management of the nonpalpable testis including novel concepts and techniques was
      synthesized. RESULTS: The nonpalpable testis should be evaluated by physical
      examination only. Imaging is not indicated for routine cases. The optimal
      surgical approach and technique remain debatable but several novel techniques
      have been described. Due to the rarity of the nonpalpable testis, randomized
      controlled trials and other quality comparisons are difficult. Therefore,
      management remains controversial. CONCLUSIONS: Evaluation and management of the
      nonpalpable testis remain difficult, and some aspects are still debated. Future
      research should focus on multi-institutional collaborative trials to determine
      the optimal operative management.

PMID- 28434987
TI  - Appraising laboratory quality and value: What's missing?

PMID- 28434988
TI  - Genotyping of Helicobacter pylori shows high diversity of strains circulating in
      central Vietnam.
AB  - In Vietnam, the high prevalence of Helicobacter pylori infection represents a
      serious health problem. Virulence genes of H. pylori have been associated to
      increased risk of severe gastrointestinal diseases and the genetic background
      differs in geographical areas. We investigated cagA and vacA genotypes of H.
      pylori from dyspeptic patients from central Vietnam and the correlation with
      clinical outcomes; we also performed sequencing analysis of partial cagA gene.
      Overall, 84% of strains were cagA-positive, 75% were East-Asian type with a
      prevalence of vacAs1i1m1 and vacAs1i1m2 genotypes (66.7% and 33.3%, respectively)
      and 9% were Western type vacAs1i1m1 (n=4) and vacAs1i1m2 (n=4); vacAs1i2m2 (n=4)
      and vacAs2i2m2 (n=2) genotypes were associated to cagA-negative. Strains from
      gastric ulcer and cancer were of East-Asian type, while cagA-negative or Western
      strains were from gastritis and duodenal ulcer. H. pylori strains from gastric
      ulcer patients were predominantly vacAs1i1m1 compared to other vacA genotypes
      (p<0.05). East-Asian type strains vacAs1i1m1 or vacAs1i1m2 were found in gastric
      cancer patients and also in less severe disease. Phylogenetic tree analysis of
      CagA sequences showed the co-circulation of H. pylori of different geographical
      origins with Western sequences closer related to Cambodia, one of the entry of
      Western strains in Southeast-Asia through human migrations. Sequence analysis
      revealed in two Western type strains a chimeric CagA-3' region with identity with
      East-Asian CagA suggesting recombination event in the process of evolution among
      East-Asian and Western H. pylori strains. Moreover, polymorphism in CagA
      multimerization (CM) motif was observed including new East-Asian CM motifs. In
      conclusion, we have found in central Vietnam a geographically dependent diversity
      of cagA genotype, with higher rates of cagA-negative and Western-type strains
      compared with other nation's parts that can partly explain the lower risk of
      gastric cancer. The polymorphism of CM motifs may explain the variability of
      disease manifestations of vacAs1i1m1 and s1i1m2 East-Asian isolates.

PMID- 28434989
TI  - Colorimetric detection of microRNA based hybridization chain reaction for signal
      amplification and enzyme for visualization.
AB  - MicroRNAs (miRNAs) have key roles in gene expression and can be employed as
      biomarkers for early diagnosis of various diseases, especially cancers. Detection
      of miRNAs remains challenging and often requires detection platforms. Here, a
      horseradish peroxidase (HRP)-assisted hybridization chain reaction (HCR) for
      colorimetric detection of miR-155 was described. In the presence of target miRNA,
      the capture probe immobilized on the microplate sandwiched the target miR-155
      with the 3' end of the reporter probe. Another exposed part of the RP at the
      5'end triggered HCR producing double-stranded DNA polymers with multiple
      fluorescein isothiocyanates (FITC) for signal amplification. Finally, multiple
      HRP molecules were immobilized onto the long-range DNA nanostructures through
      FITC/anti-FITC monoclonal antibody interactions on the microplate for
      visualization by tetramethylbenzidine/H2O2 system and the colorless substrate
      turned into the blue product. To obtain accurate data, the absorbance at 450 nm
      was calculated by microplate reader. The detection limit was 31.8 fM (3.18 amol).
      Furthermore, this biosensor showed high specificity and was able to discriminate
      sharply between target miRNA and mismatched sequences. And this approach could be
      easily applied to the detection of miR-155 in serum sample, thereby ascribing it
      for a wide application.

PMID- 28434990
TI  - Role of circadian rhythm and REM sleep for memory consolidation.
AB  - Although sleep is strongly implicated in memory consolidation, the molecular
      basis for the role of sleep in memory is not known. It has been established that
      the consolidation of hippocampus-dependent memory depends on the activation of
      the Erk1,2 MAP kinase (MAPK) pathway which activates de novo CRE-mediated
      transcription and translation, two processes required for memory consolidation
      pathway. The activation of MAPK during memory formation and its nuclear
      translocation both depend upon cAMP signals generated by the calmodulin
      stimulated adenylyl cyclases, type 1 and type 8 (AC1 and AC8). This signaling
      pathway undergoes a circadian oscillation in the hippocampus with maximal
      activation during REM sleep. This data supports the hypothesis that the
      persistence of long-term memory traces may depend upon the reactivation and
      circadian oscillation of the cAMP/MAP kinase/CRE transcriptional pathway in
      tagged neurons which reaches a maximum during REM sleep.

PMID- 28434991
TI  - The control of sleep and wakefulness by mesolimbic dopamine systems.
AB  - The mesolimbic dopamine pathway between the ventral tegmental area (VTA) and the
      nucleus accumbens (NAc) plays a central role in motivational behaviors. Recent
      findings indicate that the VTA and NAc are also involved in sleep/wake regulation
      - the topic of this review. First, we present an overview of the growing evidence
      from rodent studies revealing a wake-regulatory role of VTA dopamine neurons. We
      also discuss brain areas and their neurotransmitters or neuromodulators that may
      regulate the activity of wake-promoting VTA dopamine neurons. This is followed by
      a summary of current knowledge of the role of the NAc in regulating slow-wave
      sleep and a discussion of where and how this control of sleep physiology might be
      regulated by upstream neurotransmitters and neuromodulators, including dopamine
      and the classic somnogen adenosine.

PMID- 28434992
TI  - Promising techniques to illuminate neuromodulatory control of the cerebral cortex
      in sleeping and waking states.
AB  - Sleep, a common event in daily life, has clear benefits for brain function, but
      what goes on in the brain when we sleep remains unclear. Sleep was long regarded
      as a silent state of the brain because the brain seemingly lacks interaction with
      the surroundings during sleep. Since the discovery of electrical activities in
      the brain at rest, electrophysiological methods have revealed novel concepts in
      sleep research. During sleep, the brain generates oscillatory activities that
      represent characteristic states of sleep. In addition to electrophysiology,
      opto/chemogenetics and two-photon Ca2+ imaging methods have clarified that the
      sleep/wake states organized by neuronal and glial ensembles in the cerebral
      cortex are transitioned by neuromodulators. Even with these methods, however, it
      is extremely difficult to elucidate how and when neuromodulators spread,
      accumulate, and disappear in the extracellular space of the cortex. Thus, real
      time monitoring of neuromodulator dynamics at high spatiotemporal resolution is
      required for further understanding of sleep. Toward direct detection of
      neuromodulator behavior during sleep and wakefulness, in this review, we discuss
      developing imaging techniques based on the activation of G-protein-coupled
      receptors that allow for visualization of neuromodulator dynamics.

PMID- 28434993
TI  - Effect of rat spinal cord injury (hemisection) on the ex vivo uptake and release
      of [3H]noradrenaline from a slice preparation.
AB  - We measured the ex vivo uptake and release of [3H]noradrenaline ([3H]NA) from
      perfused rat spinal cord slice preparations at 1, 3 and 14days after unilateral
      hemisection-induced spinal cord injury (SCI) compared with control slice
      preparations. After surgical hemisection under anaesthesia, the rats showed
      characteristic signs of hemiplegia, with no movement of the ipsilateral hindlimb.
      After 3days, the electron microscopy images showed overall degeneration of
      neuronal organelles and the myelin sheath, but the synapses seemed to be intact.
      In ex vivo experiments, the spinal cord injury did not influence uptake but
      increased [3H]NA release at rest and in response to axonal stimulation. The
      effect of a selective noradrenaline reuptake inhibitor, nisoxetine, was studied
      to identify the mechanisms underlying the increase in NA release. Nisoxetine
      potentiated stimulation-evoked [3H]NA release from the non-injured tissue, but it
      gradually lost its effectiveness after injury, depending on the time (1 and
      3days) elapsed after hemisection, indicating that the noradrenaline transporter
      binding sites of the terminals become impaired after decentralisation.

PMID- 28434994
TI  - Transient upregulation of Nav1.6 expression in the genu of corpus callosum
      following middle cerebral artery occlusion in the rats.
AB  - Focal ischemic stroke can lead to brain damage and cause human disability and
      death. Increased excitatory transmission and reduced neuronal inhibition are
      important pathological alterations in the cerebral ischemia, which can induce
      abnormal brain excitability. Nav1.6 is a key determinant of neuronal excitability
      in the nervous system. Here we investigate the expression of Nav1.6 at protein
      and mRNA levels in the rats subjected to middle cerebral artery occlusion (MCAO).
      Nav1.6 expression at mRNA levels in the ischemic and contralateral hemispheres of
      MCAO rats were persistently decreased at 6h, 12h and 24h after reperfusion
      compared to the sham-operated rats. However, a prominent, dynamic increase of
      Nav1.6 immunoreactivity in reactive astrocytes was observed in the genu of corpus
      callosum (GCC) of MCAO rats in the acute phase, reaching the peak at 6h after
      reperfusion, rapidly dropping at 12h and 24h after reperfusion. Furthermore, the
      upregulation of Nav1.6 expression was strongly correlated with the severity of
      reactive astrogliosis. Collectively, these findings suggest that this upregulated
      astrocytic sodium channel expression in the GCC of MCAO rats may contribute to
      the functional roles of reactive astrocytes in response to brain ischemia.

PMID- 28434995
TI  - An SIR-Dengue transmission model with seasonal effects and impulsive control.
AB  - In recent decades, Dengue fever and its deadly complications, such as Dengue
      hemorrhagic fever, have become one of the major mosquito-transmitted diseases,
      with an estimate of 390 million cases occurring annually in over 100 tropical and
      subtropical countries, most of which belonging to the developing world. Empirical
      evidence indicates that the most effective mechanism to reduce Dengue infections
      is to combat the disease-carrying vector, which is often implemented via chemical
      pesticides to destroy mosquitoes in their adult or larval stages. The present
      paper considers an SIR epidemiological model describing the vector-to-host and
      host-to-vector transmission dynamics. The model includes pesticide control
      represented in terms of periodic impulsive perturbations, as well as seasonal
      fluctuations of the vector growth and transmission rates of the disease. The
      effectiveness of the control strategy is studied numerically in detail by means
      of path-following techniques for non-smooth dynamical systems. Special attention
      is given to determining the optimal timing of the pesticide applications, in such
      a way that the number of infections and the required amount of pesticide are
      minimized.

PMID- 28434997
TI  - Multi-photon microscopy in cardiovascular research.
AB  - Multiphoton laser scanning microscopy has proven profound value for ex vivo 3D
      histology and in vivo imaging of motionless tissue. The development of triggering
      systems and fast imaging methods, combined with advanced preparation procedures
      solved the challenging task of intravital imaging of the fast pulsating heart and
      major arteries in animals and further increased the popularity of intravital
      multiphoton imaging in cardiovascular research. This review article will
      highlight the potential of multiphoton microscopy for the visualization and
      characterization of dynamical and structural processes involved in cardiac and
      vascular diseases, both in an ex vivo and an intravital animal setting. Examples
      will be given how multiphoton microscopy can be applied to imaging of
      atherosclerotic plaque development and progression at subcellular level as well
      as to intravital imaging of inflammatory processes in the heart. In addition to
      highlighting the potential of multiphoton microscopy in preclinical
      cardiovascular research, we will discuss how this tool and its applications may
      be clinically translated to support disease diagnosis and therapy in patients.

PMID- 28434996
TI  - Effect of heparin and heparan sulphate on open promoter complex formation for a
      simple tandem gene model using ex situ atomic force microscopy.
AB  - The influence of heparin and heparan sulphate (HepS) on the appearance and
      analysis of open promoter complex (RPo) formation by E. coli RNA polymerase
      (RNAP) holoenzyme (sigma70RNAP) on linear DNA using ex situ imaging by atomic
      force microscopy (AFM) has been investigated. Introducing heparin or HepS into
      the reaction mix significantly reduces non-specific interactions of the
      sigma70RNAP and RNAP after RPo formation allowing for better interpretation of
      complexes shown within AFM images, particularly on DNA templates containing more
      than one promoter. Previous expectation was that negatively charged
      polysaccharides, often used as competitive inhibitors of sigmaRNAP binding and
      RPo formation, would also inhibit binding of the DNA template to the mica support
      surface and thereby lower the imaging yield of active RNAP-DNA complexes. We
      found that the reverse of this was true, and that the yield of RPo formation
      detected by AFM, for a simple tandem gene model containing two lambdaPR
      promoters, increased. Moreover and unexpectedly, HepS was more efficient than
      heparin, with both of them having a dispersive effect on the sample, minimising
      unwanted RNAP-RNAP interactions as well as non-specific interactions between the
      RNAP and DNA template. The success of this method relied on the observation that
      E. coli RNAP has the highest affinity for the mica surface of all the molecular
      components. For our system, the affinity of the three constituent biopolymers to
      muscovite mica was RNAP>Heparin or HepS>DNA. While we observed that heparin and
      HepS can inhibit DNA binding to the mica, the presence of E. coli RNAP overcomes
      this effect allowing a greater yield of RPos for AFM analysis. This method can be
      extended to other DNA binding proteins and enzymes, which have an affinity to
      mica higher than DNA, to improve sample preparation for AFM studies.

PMID- 28434998
TI  - Use of two-photon microscopy to study Leishmania major infection of the skin.
AB  - Intra-vital two-photon microscopy (2P-IVM) allows for in-situ investigation of
      tissue organization, cell behavior and the dynamic interactions between different
      cell types in their natural environment. This methodology has also expanded our
      understanding of the immune response against pathogens. Leishmania are protozoan
      intracellular parasites that have adapted to successfully establish infection
      within the context of an inflammatory response in the skin following transmission
      by the bite of an infected sand fly. The generation of fluorescent transgenic
      parasites coupled with the increased availability of different types of
      fluorescent transgenic reporter mice has facilitated the study of the host
      parasite interaction in the skin, significantly impacting our understanding of
      cutaneous leishmaniasis. In this review we will discuss 2P-IVM in the context of
      Leishmania infection of the mouse ear skin and describe a simple and minimally
      invasive procedure that allows long-term imaging of this host-pathogen
      interaction.

PMID- 28434999
TI  - smFRET experiments of the RNA polymerase II transcription initiation complex.
AB  - Single-molecule fluorescence and in particular single-molecule Forster Resonance
      Energy Transfer (smFRET) is a powerful tool to provide real-time information on
      the dynamic architecture of large macromolecular structures such as eukaryotic
      transcription initiation complexes. In contrast to other structural biology
      methods, not only structural details, but dynamics transitions are revealed thus
      closing in on the underlying molecular mechanisms. Here, we describe a
      comprehensive quantitative biophysical toolbox which can be used for rigorous
      analysis of dynamic protein-nucleic acid complexes and is applied to the study of
      eukaryotic transcription initiation. We present detailed protocols for the
      purification of all essential protein components of the minimal eukaryotic
      transcription initiation complex. Moreover, we demonstrate how elaborate
      strategies for site-specific protein labeling can be used to produce complexes
      with dye molecules attached to arbitrary desired positions. These complexes are
      then used for smFRET measurements. Moreover, we describe the Nano-Positioning
      System (NPS) which allows us to quantitatively use the results from a network of
      smFRET measurements to obtain structural information. With this we provide a
      toolbox to answer open questions which could not be addressed using methods like
      X-ray crystallography or cryo-electron microscopy.

PMID- 28435000
TI  - Context-dependent intravital imaging of therapeutic response using intramolecular
      FRET biosensors.
AB  - Intravital microscopy represents a more physiologically relevant method for
      assessing therapeutic response. However, the movement into an in vivo setting
      brings with it several additional considerations, the primary being the context
      in which drug activity is assessed. Microenvironmental factors, such as hypoxia,
      pH, fibrosis, immune infiltration and stromal interactions have all been shown to
      have pronounced effects on drug activity in a more complex setting, which is
      often lost in simpler two- or three-dimensional assays. Here we present a
      practical guide for the application of intravital microscopy, looking at the
      available fluorescent reporters and their respective expression systems and
      analysis considerations. Moving in vivo, we also discuss the microscopy set up
      and methods available for overlaying microenvironmental context to the
      experimental readouts. This enables a smooth transition into applying higher
      fidelity intravital imaging to improve the drug discovery process.

PMID- 28435002
TI  - Systemic arterial hypertension secondary to chronic kidney disease in two captive
      born large felids.
AB  - Systemic arterial hypertension (SHT) has been widely described in the domestic
      cat (Felis catus). In these feline patients, SHT is considered as the most common
      vascular disorder of middle-aged to older animals, and secondary SHT related to
      chronic kidney disease (CKD) represents the most common form of the disease. We
      describe here the first two cases of spontaneous SHT in large felids, i.e. one 18
      year old, 34.4 kg, male North-Chinese leopard (Panthera pardus japonensis, case
      #1) and one 20-year old, 28.7 kg, female snow leopard (Panthera uncia, case #2),
      both captive-bred and previously diagnosed with CKD. Both animals underwent
      complete echocardiographic examination under general anesthesia due to abnormal
      cardiac auscultation (heart murmur and/or gallop sound), and recurrent lethargy
      in case #1. The combination of left ventricular remodeling with moderate aortic
      regurgitation of high velocity was highly suggestive of SHT, which was confirmed
      by indirect blood pressure measurement (systolic arterial blood pressure of 183
      mmHg for case #1 and 180 mmHg for case #2). Amlodipine was prescribed (0.35-0.70
      mg/kg/day orally) for 31 and 6 months respectively after the initial diagnosis.
      In case #1, concurrent amlodipine and benazepril treatment was associated with
      decreased heart murmur grade and reduced aortic insufficiency severity. These
      reports illustrate that, similarly to domestic cats, SHT should be suspected in
      old large felids with CKD and that amlodipine is a well-tolerated
      antihypertensive drug in these species.

PMID- 28435001
TI  - Hi-C 2.0: An optimized Hi-C procedure for high-resolution genome-wide mapping of
      chromosome conformation.
AB  - Chromosome conformation capture-based methods such as Hi-C have become mainstream
      techniques for the study of the 3D organization of genomes. These methods convert
      chromatin interactions reflecting topological chromatin structures into digital
      information (counts of pair-wise interactions). Here, we describe an updated
      protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single
      protocol for efficient and high-resolution capture of chromatin interactions.
      This protocol combines chromatin digestion and frequently cutting enzymes to
      obtain kilobase (kb) resolution. It also includes steps to reduce random ligation
      and the generation of uninformative molecules, such as unligated ends, to improve
      the amount of valid intra-chromosomal read pairs. This protocol allows for
      obtaining information on conformational structures such as compartment and
      topologically associating domains, as well as high-resolution conformational
      features such as DNA loops.

PMID- 28435003
TI  - The Hemodynamic Effects of Aortic Insufficiency in Patients Supported With
      Continuous-Flow Left Ventricular Assist Devices.
AB  - BACKGROUND: The impact of aortic insufficiency (AI) on the morbidity and
      mortality of left ventricular assist device (LVAD) patients remains
      controversial. This study's aim was to assess the hemodynamics of LVAD patients
      with at least mild AI, at baseline and in response to device speed changes.
      METHODS AND RESULTS: Asymptomatic LVAD patients were prospectively enrolled and
      underwent a hemodynamic and echocardiographic ramp study. Hemodynamics at rest
      and in response to device speed changes were compared between patients with at
      least mild AI at their baseline speed and patients without AI. Fift-five patients
      were enrolled in the study, and 42% had AI. The AI group had higher baseline
      central venous pressure (11 +/- 5 vs 8 +/- 5 mm Hg; P = .03), higher pulmonary
      capillary wedge pressure (PCWP) (16 +/- 6 vs 12 +/- 6 mm Hg; P = .02) and lower
      pulmonary artery pulsatility index (PAPI) (2.3 +/- 1.3 vs 3.6 +/- 2.4; P = .01).
      Cardiac index (CI) increased and PCWP decreased in both groups by similar degrees
      during the ramp study. AI worsened in 78% of patients during the ramp study.
      CONCLUSIONS: LVAD patients with at least mild AI have increased filling pressures
      and reduced PAPI. Normalization of filling pressures can be achieved by
      increasing LVAD speed; however, this concomitantly worsens AI severity. The long
      term hemodynamic consequences of this approach are unknown.

PMID- 28435005
TI  - Lessons in Bridge-Building: A Multidisciplinary Approach to Heart Failure Care.

PMID- 28435004
TI  - Improvements in Left Ventricular Diastolic Mechanics After Parachute Device
      Implantation in Patients With Ischemia Heart Failure: A Cardiac Computerized
      Tomographic Study.
AB  - BACKGROUND: Percutaneous ventricular restoration therapy with the use of a left
      ventricle (LV)-partitioning Parachute device has emerged as a clinical treatment
      option for LV apical aneurysm after extensive anterior myocardial infarction
      (AMI). We assessed changes of diastolic mechanics and functional improvements
      following LV Parachute device implantation by means of cardiac computerized
      tomography (CCT). METHODS AND RESULTS: CCT data were obtained from 28 patients
      before and after LV Parachute device implantation. Diastolic functional indices
      were determined by means of quantitative CCT assessment: 1) transmitral
      velocities in early (E) and late (A) diastole and ratio (E/A); 2) early diastolic
      mitral septal tissue velocity (Ea) and E/Ea; and 3) vortex formation time (VFT).
      Functional improvements were assessed with the use of New York Heart Association
      (NYHA) functional classification. Among the study patients, there were no
      significant differences in all transmitral velocities and E/A, though there was
      significantly increased Ea, reduced E/Ea, and greater VFT 6 months after LV
      Parachute device implantation. Finally, the improvement of diastolic functional
      indices after Parachute treatment correlated with observed clinical functional
      alterations (Delta E/Ea and Delta NYHA functional class:, r = 0.563; P = .002;
      Delta VFT and Delta NYHA functional class: r = -0.507; P = .006). CONCLUSIONS: LV
      Parachute device implantation therapy in heart failure caused by AMI and LV
      apical aneurysm formation showed improvements in several diastolic functional
      mechanics according to CCT-based measures.

PMID- 28435006
TI  - Horizontal transfer of chromosomal markers mediated by the large conjugative
      plasmid pXO16 from Bacillus thuringiensis serovar israelensis.
AB  - pXO16, a large plasmid originating from Bacillus thuringiensis serovar
      israelensis, displays unique conjugation capacities: besides efficient self
      transfer, it is able to mobilize and retro-mobilize non-conjugative plasmids,
      including those missing an oriT and/or a mob gene, also known as "non
      mobilizable" plasmids. In this paper, another peculiar transfer property of pXO16
      is described. This element is indeed able to transfer chromosomal loci at
      frequencies of ca. 10-5-10-6 transconjugants/donor cell. Whereas most other
      chromosomal transfer systems occur via the integration of the conjugative
      elements into the chromosome prior to its transfer, pXO16 appears to transfer the
      chromosomal markers in the absence of physical integration, but rather through a
      "donation-type" mobilization.

PMID- 28435007
TI  - Stem cells and their potential clinical applications in psychiatric disorders.
AB  - The robustness of stem cells is one of the major factors that directly impacts
      life quality and life span. Evidence has accumulated that changes in the stem
      cell compartment affect human mental health and serve as an indicator of
      psychiatric problems. It is well known that stem cells continuously replace
      differentiated cells and tissues that are used up during life, although this
      replacement occurs at a different pace in the various organs. However, the
      participation of local neural stem cells in regeneration of the central nervous
      system is controversial. It is known that low numbers of stem cells circulate
      continuously in peripheral blood (PB) and lymph and undergo a circadian rhythm in
      their PB level, with the peak occurring early in the morning and the nadir at
      night, and recent evidence suggests that the number and pattern of circulating
      stem cells in PB changes in psychotic disorders. On the other hand, progress in
      the creation of induced pluripotent stem cells (iPSCs) from patient somatic cells
      provides valuable tools with which to study changes in gene expression in
      psychotic patients. We will discuss the various potential sources of stem cells
      that are currently employed in regenerative medicine and the mechanisms that
      explain some of their beneficial effects as well as the emerging problems with
      stem cell therapies. However, the main question remains: Will it be possible in
      the future to modulate the stem cell compartment to reverse psychiatric problems?

PMID- 28435008
TI  - Cortical and amygdalar neuronal ensembles in alcohol seeking, drinking and
      withdrawal.
AB  - Alcohol induces many alterations in the brain that are thought to contribute to
      alcohol addiction. Most of the known alterations are induced in all neurons of a
      brain area or all neurons of a given cell type, regardless of whether they were
      activated during behavior. While these alterations can have important modulatory
      effects on behavior, they cannot explain why animals respond specifically to
      alcohol-paired cues as opposed to all other non-paired cues and evoke highly
      specific goal-directed learned responses in models of drug craving. As an
      alternative, we hypothesize another class of alterations that are induced only
      within sparsely distributed patterns of neurons, called neuronal ensembles, that
      are selectively activated by alcohol-specific cues during behavior and encode the
      long-term memories underlying these learned behaviors in animal models of alcohol
      addiction. Here we review recent studies and techniques used to identify the role
      of neuronal ensembles in animal models of different phases of the alcohol
      addiction cycle. This article is part of the Special Issue entitled "Alcoholism".

PMID- 28435009
TI  - Selective small-molecule inhibitors as chemical tools to define the roles of
      matrix metalloproteinases in disease.
AB  - The focus of this article is to highlight novel inhibitors and current examples
      where the use of selective small-molecule inhibitors has been critical in
      defining the roles of matrix metalloproteinases (MMPs) in disease. Selective
      small-molecule inhibitors are surgical chemical tools that can inhibit the
      targeted enzyme; they are the method of choice to ascertain the roles of MMPs and
      complement studies with knockout animals. This strategy can identify targets for
      therapeutic development as exemplified by the use of selective small-molecule MMP
      inhibitors in diabetic wound healing, spinal cord injury, stroke, traumatic brain
      injury, cancer metastasis, and viral infection. This article is part of a Special
      Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.

PMID- 28435010
TI  - Ribotypes associated with Clostridium difficile outbreaks in Brazil display
      distinct surface protein profiles.
AB  - Clostridium difficile is a spore-forming anaerobic intestinal pathogen that
      causes Clostridium difficile infection (CDI). C. difficile is the leading cause
      of toxin-mediated nosocomial antibiotic-associated diarrhea. The pathogenesis of
      CDI is attributed to two major virulence factors, TcdA and TcdB toxins, that
      cause the symptomatic infection. C. difficile also expresses a number of key
      proteins, including cell wall proteins (CWPs). S-layer proteins (SLPs) are CWPs
      that form a paracrystalline surface array that coats the surface of the
      bacterium. SLPs have a role in C. difficile binding to the gastrointestinal
      tract, but their importance in virulence need to be better elucidated. Here, we
      describe bottom-up proteomics analysis of surface-enriched proteins fractions
      obtained through glycine extraction of five C. difficile clinical isolates from
      Brazil using gel-based and gel-free approaches. We were able to identify
      approximately 250 proteins for each strain, among them SlpA, Cwp2, Cwp6, CwpV and
      Cwp84. Identified CWPs presented different amino acid coverage, which might
      suggest differences in post-translational modifications. Proteomic analysis of
      SLPs from ribotype 133, agent of C. difficile outbreaks in Brazil, revealed
      unique proteins and provided additional information towards in depth
      characterization of the strains causing CDI in Brazil.

PMID- 28435011
TI  - The in vitro activity of ceftazidime-avibactam against 417 Gram-negative bacilli
      collected in 2014 and 2015 at a teaching hospital in Sao Paulo, Brazil.

PMID- 28435012
TI  - IL-10 down-regulates the expression of survival associated gene hspX of
      Mycobacterium tuberculosis in murine macrophage.
AB  - Mycobacterium tuberculosis (MTB) adopts a special survival strategy to overcome
      the killing mechanism(s) of host immune system. Amongst the many known factors,
      small heat shock protein 16.3 (sHSP16.3) of MTB encoded by gene hspX has been
      reported to be critical for the survival of MTB. In the present study, the effect
      of recombinant murine interferon-gamma (rmIFN-gamma) and recombinant murine
      interleukin-10 (rmIL-10) on the expression of gene hspX of MTB in murine
      macrophage RAW264.7 has been investigated. By real-time RT-PCR, it was observed
      that three increasing concentrations (5, 25 and 50ng/ml) of rmIFN-gamma
      significantly up-regulated the expression of hspX whereas similar concentrations
      of rmIL-10 (5, 25 and 50ng/ml) significantly down-regulated the hspX expression.
      This effect was not only dependent on the concentration of the stimulus but this
      was time-dependent as well. A contrasting pattern of hspX expression was observed
      against combinations of two different concentrations of rmIFN-gamma and rmIL-10.
      The study results suggest that rIL-10 mediated down-regulation of hspX
      expression, in the presence of low concentration of rIFN-gamma, could be used as
      an important strategy to decrease the dormancy of MTB in its host and thus making
      MTB susceptible to the standard anti-mycobacterial therapy used for treating
      tuberculosis. However, as these are only preliminary results in the murine cell
      line model, this hypothesis needs to be first validated in human cell lines and
      subsequently in animal models mimicking the latent infection using clinical
      isolates of MTB before considering the development of modified regimens for
      humans.

PMID- 28435013
TI  - Modeling Chagas disease in Chile: From vector to congenital transmission.
AB  - Chagas disease is a human health problem in Latin America. It is highly prevalent
      in northern Chile between the Arica-Parinacota and Coquimbo regions, with
      reported incidence of 3-11/100000 inhabitants and mortality of 0.3-0.4/100000.
      The interruption of vector transmission was reported in 1999 by means of the
      elimination of the primary vector, Triatoma infestans, from human dwellings, thus
      the epidemiologic dynamics of this disease should be modified. Here we model the
      dynamics of Chagas disease based on previous models for vector and congenital
      transmission, propose a model that includes both transmission forms and perform
      simulations. We derive useful relationships for the reproductive number (R0)
      showing that it may be expressed as the sum of the vector (R0V) and congenital
      (R0C) contributions. The vector contribution is larger than the congenital one;
      without the former Chagas disease vanishes exponentially in two to three
      generations. Sensitivity analyses showed that the main parameters that intervene
      are the human bite rate, the density of vectors per human and the mortality rate
      of the insect vectors. Our model showed that the success of the eradication of
      Chagas disease is based on the interruption of domestic transmission. Once this
      is obtained, the control strategies should focus on avoiding the domiciliation of
      wild vectors, re-colonization by the primary vector, and an adequate coverage of
      congenital case treatment.

PMID- 28435014
TI  - Maximum likelihood estimates of pairwise rearrangement distances.
AB  - Accurate estimation of evolutionary distances between taxa is important for many
      phylogenetic reconstruction methods. Distances can be estimated using a range of
      different evolutionary models, from single nucleotide polymorphisms to large
      scale genome rearrangements. Corresponding corrections for genome rearrangement
      distances fall into 3 categories: Empirical computational studies, Bayesian/MCMC
      approaches, and combinatorial approaches. Here, we introduce a maximum likelihood
      estimator for the inversion distance between a pair of genomes, using a group
      theoretic approach to modelling inversions introduced recently. This MLE
      functions as a corrected distance: in particular, we show that because of the way
      sequences of inversions interact with each other, it is quite possible for
      minimal distance and MLE distance to differently order the distances of two
      genomes from a third. The second aspect tackles the problem of accounting for the
      symmetries of circular arrangements. While, generally, a frame of reference is
      locked, and all computation made accordingly, this work incorporates the action
      of the dihedral group so that distance estimates are free from any a priori frame
      of reference. The philosophy of accounting for symmetries can be applied to any
      existing correction method, for which examples are offered.

PMID- 28435015
TI  - Using classification models for the generation of disease-specific medications
      from biomedical literature and clinical data repository.
AB  - OBJECTIVE: Mining disease-specific associations from existing knowledge resources
      can be useful for building disease-specific ontologies and supporting knowledge
      based applications. Many association mining techniques have been exploited.
      However, the challenge remains when those extracted associations contained much
      noise. It is unreliable to determine the relevance of the association by simply
      setting up arbitrary cut-off points on multiple scores of relevance; and it would
      be expensive to ask human experts to manually review a large number of
      associations. We propose that machine-learning-based classification can be used
      to separate the signal from the noise, and to provide a feasible approach to
      create and maintain disease-specific vocabularies. METHOD: We initially focused
      on disease-medication associations for the purpose of simplicity. For a disease
      of interest, we extracted potentially treatment-related drug concepts from
      biomedical literature citations and from a local clinical data repository. Each
      concept was associated with multiple measures of relevance (i.e., features) such
      as frequency of occurrence. For the machine purpose of learning, we formed nine
      datasets for three diseases with each disease having two single-source datasets
      and one from the combination of previous two datasets. All the datasets were
      labeled using existing reference standards. Thereafter, we conducted two
      experiments: (1) to test if adding features from the clinical data repository
      would improve the performance of classification achieved using features from the
      biomedical literature only, and (2) to determine if classifier(s) trained with
      known medication-disease data sets would be generalizable to new disease(s).
      RESULTS: Simple logistic regression and LogitBoost were two classifiers
      identified as the preferred models separately for the biomedical-literature
      datasets and combined datasets. The performance of the classification using
      combined features provided significant improvement beyond that using biomedical
      literature features alone (p-value<0.001). The performance of the classifier
      built from known diseases to predict associated concepts for new diseases showed
      no significant difference from the performance of the classifier built and tested
      using the new disease's dataset. CONCLUSION: It is feasible to use classification
      approaches to automatically predict the relevance of a concept to a disease of
      interest. It is useful to combine features from disparate sources for the task of
      classification. Classifiers built from known diseases were generalizable to new
      diseases.

PMID- 28435016
TI  - The angiostatic molecule Multimerin 2 is processed by MMP-9 to allow sprouting
      angiogenesis.
AB  - Angiogenesis is a crucial process occurring under physiological and pathological
      conditions, including cancer. The development of blood vessels is tightly
      regulated by a plethora of cytokines, endothelial cell (EC) receptors and
      extracellular matrix (ECM) components. In this context, we have shown that
      Multimerin 2 (MMRN2), an ECM molecule specifically secreted by ECs, exerts
      angiostatic functions by binding VEGFA and other pro-angiogenic cytokines. Here,
      we demonstrate that during angiogenic stimuli MMRN2 mRNA levels significantly
      decrease. Furthermore, we provide evidence that MMRN2 is processed by matrix
      metalloproteinases (MMPs) including MMP-9 and, to a lesser degree, by MMP-2. This
      proteolytic cleavage correlates with an increased migration of ECs. Accordingly,
      MMRN2 down-regulation is associated with an increased number of EC pseudopodia at
      the migrating front and this effect is attenuated using specific MMP-9
      inhibitors. The down-modulation of MMRN2 occurs also in the context of tumor
      associated angiogenesis. Immunofluorescence performed on tumor sections indicate
      a broad co-localization of MMP-9 and MMRN2, suggesting that the molecule may be
      extensively remodeled during tumor angiogenesis. Given the altered expression in
      tumors and the key role of MMRN2 in blood vessel function, we postulate that
      analyses of its expression may serve as a marker to predict the efficacy of the
      treatments. In conclusion, these data further support the role of MMRN2 as a key
      molecule regulating EC function and sprouting angiogenesis.

PMID- 28435017
TI  - Association of paraoxonase 1 and oxidative stress with acute kidney injury in
      premature asphyxiated neonates.
AB  - OBJECTIVES: Acute kidney injury (AKI) is defined as a decrease in glomerular
      filtration rate with an increase in serum creatinine (sCr). Perinatal asphyxia
      (PNA) may be etiological factor for AKI with oxidative stress also implicated.
      Paraoxonase 1 (PON1) activity has been reported to be decreased in renal disease.
      The aim of our study was to evaluate paraoxonase 1 (PON1) activity and oxidative
      stress during the first hours and first days of life and to determine if these
      parameters could discriminate neonates having AKI from those who do not. METHODS:
      Serum samples at different time points after birth were obtained from 64 preterm
      newborns with PNA (45 defined as having AKI, 19 as non-AKI). Clinical markers,
      sCr, total oxidant status (TOS), total antioxidant status (TAS) and PON1 activity
      were measured. RESULTS: The AKI group had more newborns with hypoxic ischemic
      encephalopathy, significantly higher serum creatinine (sCr) at 3 and 7d, total
      antioxidant status (TAS) at 7d; decreased PON1 at 4h, 6h and 7d than the non-AKI
      group. Within the AKI group, significant positive correlations were found between
      PON1 activity at 2h and TAS at 2h, PON1 activity at 4h and base deficit (BD);
      whereas negative correlations between PON1 activity at 2h and DeltasCr (at 24h
      and at 3d), PON1 activity at 7d and DeltasCr (at 24h and 3d). Oxidative stress
      status parameters indicated excellent discriminative potential at 4h, 6h and 7d.
      CONCLUSIONS: AKI neonates were characterised by a marked decrease in PON1
      activity. PON1 activity may be an important factor for discrimination of newborns
      having AKI from those that do not.

PMID- 28435018
TI  - NDM-5-producing Escherichia coli in an urban river in Montpellier, France.

PMID- 28435019
TI  - Epidemiology and trends in the antibiotic susceptibilities of Gram-negative
      bacilli isolated from patients with intra-abdominal infections in the Asia
      Pacific region, 2010-2013.
AB  - This study was conducted to investigate the epidemiology and antimicrobial
      susceptibility patterns of Gram-negative bacilli (GNB) isolated from intra
      abdominal infections (IAIs) in the Asia-Pacific region (APR) from 2010-2013. A
      total of 17 350 isolates were collected from 54 centres in 13 countries in the
      APR. The three most commonly isolated GNB were Escherichia coli (46.1%),
      Klebsiella pneumoniae (19.3%) and Pseudomonas aeruginosa (9.8%). Overall, the
      rates of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K.
      pneumoniae were 38.2% and 24.3%, respectively, and they were highest in China
      (66.6% and 38.7%, respectively), Thailand (49.8% and 36.5%, respectively) and
      Vietnam (47.9% and 30.4%, respectively). During 2010-2013, the rates of ESBL
      producing E. coli and K. pneumoniae isolates causing community-associated (CA)
      IAIs (collected <48 h after admission) were 26.0% and 13.5%, respectively, and
      those causing hospital-associated (HA) IAIs were 48.0% and 30.6%, respectively.
      Amikacin, ertapenem and imipenem were the most effective agents against ESBL
      producing isolates. Piperacillin/tazobactam displayed good in vitro activity
      (91.4%) against CA ESBL-producing E. coli. For other commonly isolated
      Enterobacteriaceae, fluoroquinolones, cefepime and carbapenems exhibited better
      in vitro activities than third-generation cephalosporins. Amikacin possessed high
      in vitro activity against all GNB isolates (>80%) causing IAIs, except for
      Acinetobacter calcoaceticus-baumannii (ACB) complex (30.9% for HA-IAI isolates).
      All of the antimicrobial agents tested exhibited <45% in vitro activity against
      ACB complex. Antimicrobial resistance is a persistent threat in the APR and
      continuous monitoring of evolutionary trends in the susceptibility patterns of
      GNB causing IAIs in this region is mandatory.

PMID- 28435020
TI  - Migrant health-a cause for concern?

PMID- 28435021
TI  - The mTORC2/PKC pathway sustains compensatory insulin secretion of pancreatic beta
      cells in response to metabolic stress.
AB  - BACKGROUND: Compensation of the pancreatic beta cell functional mass in response
      to metabolic stress is key to the pathogenesis of Type 2 Diabetes. The mTORC2
      pathway governs fuel metabolism and beta cell functional mass. It is unknown
      whether mTORC2 is required for regulating metabolic stress-induced beta cell
      compensation. METHODS: We challenged four-week-old beta-cell-specific Rictor (a
      key component of mTORC2)-knockout mice with a high fat diet (HFD) for 4weeks and
      measured metabolic and pancreatic morphological parameters. We performed ex vivo
      experiments to analyse beta cell insulin secretion and electrophysiology
      characteristics. Adenoviral-mediated overexpression and lentiviral-ShRNA-mediated
      knocking down proteins were applied in Min6 cells and cultured primary mouse
      islets. RESULTS: betaRicKO mice showed a significant glucose intolerance and a
      reduced plasma insulin level and an unchanged level beta cell mass versus the
      control mice under HFD. A HFD or palmitate treatment enhanced both glucose
      induced insulin secretion (GIIS) and the PMA (phorbol 12-myristate 13-acetate)
      induced insulin secretion in the control islets but not in the betaRicKO islets.
      The KO beta cells showed similar glucose-induced Ca2+ influx but lower membrane
      capacitance increments versus the control cells. The enhanced mTORC2/PKC proteins
      levels in the control HFD group were ablated by Rictor deletion. Replenishing
      PKCalpha by overexpression of PKCalpha-T638D restored the defective GIIS in
      betaRicKO islets. CONCLUSIONS: The mTORC2/Rictor pathway modulates beta cell
      compensatory GIIS under nutrient overload mediated by its phosphorylation of
      PKCalpha. GENERAL SIGNIFICANCE: This study suggests that the mTORC2/PKC pathway
      in beta cells is involved in the pathogenesis of T2D.

PMID- 28435022
TI  - Maternal separation induces hippocampal changes in cadherin-1 (CDH-1) mRNA and
      recognition memory impairment in adolescent mice.
AB  - In rodents, disruption of mother-infant attachment induced by maternal separation
      (MS) is associated with recognition memory impairment and long-term
      neurobiological consequences. Particularly stress-induced modifications have been
      associated to disruption of cadherin (CDH) adhesion function, which plays an
      important role in remodeling of neuronal connection and synaptic plasticity. This
      study investigated the sex-dependent effect of MS on recognition memory and mRNA
      levels of classical type I and type II CDH and the related beta -catenin (beta 
      Cat) in the hippocampus and prefrontal cortex of late adolescent mice. We
      provided evidence that the BALB/c mice exposed to MS present deficit in
      recognition memory, especially females. Postnatal MS induced higher hippocampal
      CDH-2 and CDH-8 mRNA levels, as well as an upregulation of CDH-1 in the
      prefrontal cortex in both males and females. MS-reared female mice presented
      lower CDH-1 mRNA levels in the hippocampus. In addition, hippocampal CDH-1 mRNA
      levels were positively correlated with recognition memory performance in females.
      MS-reared male mice exhibited higher beta -Cat mRNA levels in the hippocampus.
      Considering sex-specific effects on CDH mRNA levels, it has been demonstrated
      mRNA changes in CDH-1, beta -Cat, and CDH-6 in the hippocampus, as well as CDH-1,
      CDH-8 and CDH-11 in the prefrontal cortex. Overall, these findings suggest a
      complex interplay among MS, CDH mRNA expression, and sex differences in the PFC
      and hippocampus of adolescent mice.

PMID- 28435023
TI  - The clinical significance of neutrophilic pleocytosis in cerebrospinal fluid in
      patients with viral central nervous system infections.
AB  - BACKGROUND: Viral central nervous system (CNS) infections are typically
      characterized by a cerebrospinal fluid (CSF) lymphocytic pleocytosis. A CSF
      neutrophilic pleocytosis presentation has been described, but its prognostic and
      clinical significance is unknown. The objectives of this study were to (1)
      compare the clinical and laboratory characteristics of viral CNS infections with
      a CSF neutrophilic pleocytosis to those with a lymphocytic pleocytosis, and (2)
      evaluate factors associated with an adverse clinical outcome. METHODS: A
      retrospective study of patients with confirmed viral CNS infections was
      conducted. The patients were divided into those with CSF neutrophilic pleocytosis
      and those with CSF lymphocytic pleocytosis. Clinical findings and outcomes were
      compared between the two groups. RESULTS: Of the 182 patients included in the
      study, 45 (24.7%) had CSF neutrophilic pleocytosis. Enterovirus infections were
      the cause of 64% of neutrophil-predominant CSF and 33% of lymphocyte-predominant
      CSF (p<0.001), while herpes infections were the cause of 46% of lymphocytic
      pleocytosis and 20% of neutrophilic pleocytosis (p=0.003). Moreover, neutrophilic
      pleocytosis was seen more commonly in younger patients (p=0.001), patients with
      respiratory symptoms (p=0.04), and patients with higher CSF white cell counts
      (p=0.004). Twenty-nine patients had an adverse clinical outcome (15.9%); the only
      predictor independently associated with an adverse clinical outcome on
      multivariable logistic regression analysis was an encephalitis presentation
      (p=0.01). CONCLUSIONS: The results of a study exploring the association between
      CSF neutrophilic pleocytosis and clinical and prognostic significance are
      presented here. This study suggests that CSF neutrophilic pleocytosis is not
      associated with higher adverse clinical outcomes.

PMID- 28435025
TI  - 3D printing in surgery - The evolving paradigm-shift in surgical implants on
      demand.

PMID- 28435024
TI  - Lkb1 deletion in murine B lymphocytes promotes cell death and cancer.
AB  - LKB1 (also known as STK11) is a potent tumor suppressor in solid tumors, such as
      melanoma and lung adenocarcinoma, but inactivation in hematopoietic cells causes
      cell death without signs of tumorigenesis. We noted somatic LKB1 deletion or
      mutation at low frequency in human B-cell lymphoma. To determine if LKB1
      inactivation is a passenger or driver event in lymphoid cancers, we examined the
      effects of conditional inactivation of Lkb1 in murine lymphocytes. Consistent
      with prior reports, Lkb1 deletion in either T or B cells resulted in massive,
      lineage-specific apoptosis. Surprisingly, despite an 80% reduction of peripheral
      B-cell number, animals harboring somatic B-lineage Lkb1 deletion developed
      aggressive B-cell lymphoma with high penetrance and moderate latency. Malignant B
      cells exhibited somatic Lkb1 recombination. In contrast, Lkb1 deletion in T cells
      did not promote tumorigenesis. Concomitant Ras activation with Lkb1 deletion
      reduced T-cell apoptosis, but did not enhance tumor formation in T or B cells.
      These results suggest that although physiologic LKB1 expression exerts a potent
      pro-survival effect in lymphocytes, LKB1 inactivation nonetheless facilitates
      transformation of B, but not T, lymphocytes.

PMID- 28435026
TI  - Complications in the anterior approach to the cervical spine: Which factors
      matter?

PMID- 28435027
TI  - Exercise-modulated epigenetic markers and inflammatory response in COPD
      individuals: A pilot study.
AB  - The study investigated the effects of exercise on epigenetic signals and systemic
      cytokine levels in chronic obstructive pulmonary disease (COPD) individuals. Ten
      participants of a pulmonary rehabilitation program were submitted to 24 sessions
      of a supervisioned exercise protocol thrice-weekly (90min/session). Blood samples
      were collected at baseline, after the 1st session, before and after the 24th
      session. A DNA hypomethylation status was observed after the 1st session when
      compared at baseline, while global histone H4 acetylation status was unaltered in
      any time-points evaluated. No significant changes were observed on cytokine
      levels after the 1st session. A significant enhancement on interleukin 6 (IL-6)
      and a decrease on transforming growth factor-beta (TGF-beta) levels were found
      after the 24th session when compared to the pre 24th session. Moreover, 23
      sessions of exercise were able to diminish significantly the basal levels of IL-6
      and interleukin 8 (IL-8). These data suggest a potential role of epigenetic
      machinery in mediating the anti-inflammatory effects of exercise in COPD
      patients.

PMID- 28435028
TI  - Antagonistic Effects of p53 and HIF1A on microRNA-34a Regulation of PPP1R11 and
      STAT3 and Hypoxia-induced Epithelial to Mesenchymal Transition in Colorectal
      Cancer Cells.
AB  - BACKGROUND & AIMS: In colorectal tumors, hypoxia causes resistance to therapy and
      promotes metastasis. Loss of the tumor suppressor p53 (encoded by TP53) provides
      cancer cells with a selective advantage under conditions of hypoxia, but little
      is known about the mediators of this effect. METHODS: Isogenic colorectal cancer
      (CRC) cell lines with different TP53 genotypes were placed under conditions of
      hypoxia. We examined the effects on levels and activity of microRNA-34a (MIR34A)
      in CRC cells. We determined the expression and localization of protein
      phosphatase 1 regulatory inhibitor subunit 11 (PPP1R11, also called INH3, HCGV,
      IPP3, HCGV, TCTE5, TCTEX5, or CFAP255) in 82 human colon cancers. We analyzed
      data on human colorectal carcinomas from the Cancer Genome Atlas collection to
      determine whether expression of PPP1R11 was affected by altered level or activity
      of p53, markers of epithelial-to-mesenchymal transition (EMT), or MIR34A or was
      associated with metastasis. We determined the effects of disruption Mir34a,
      Mir34b, and Mir34c in ApcMin/+ mice. DLD-1 cells were transfected with small
      inhibitor RNAs against PPP1R1, injected into the tail veins of immune-compromised
      mice, and followed by noninvasive bioluminescence imaging. RESULTS: The hypoxia
      inducible factor 1 alpha subunit (HIF1A) directly repressed the MIR34A gene in
      p53-defective CRC cells, whereas expression of MIR34A was induced in p53
      proficient CRC cells exposed to hypoxia. Down-regulation of MIR34A was required
      for hypoxia-induced EMT, invasion and migration, and activation of STAT3 in CRC
      cells. We identified PPP1R11, whose product inhibits PP1, as a target of MIR34A.
      PPP1R11 mediates phosphorylation (activation) of STAT3, so expression of MIR34A
      reduced activation of STAT3 in p53-deficient CRC cells. Ectopic expression of
      PPP1R11 in CRC cells induced EMT, invasion, and migration, which all required
      STAT3. Increased expression of PPP1R11 in p53-deficient CRC cells was required
      for hypoxia-induced EMT, invasion, migration, and resistance to 5-fluorouracil,
      as well as metastasis of xenograft tumors to lungs of mice. Adenomas and derived
      tumoroids of ApcMin/+ mice with disruption of Mir34a, Mir34b, and Mir34c had
      increased levels of PPP1R11. Colorectal tumors from patients had increased levels
      of PPP1R11 at areas of invasion, compared with other areas of the tumor;
      increased level PPP1R11 associated with TP53 mutations and metastasis to the
      liver. CONCLUSIONS: HIF1A represses, whereas p53 increases, expression of MIR34A
      in CRC cells. MIR34A reduces expression of PPP1R11 to prevent activation of STAT3
      and inhibit the EMT and metastasis. Strategies to target this pathway might be
      developed to inhibit CRC metastasis and overcome resistance to therapy associated
      with hypoxia.

PMID- 28435029
TI  - Activity of carboxylesterases, glutathione-S-transferase and monooxygenase on
      Rhipicephalus microplus exposed to fluazuron.
AB  - The objective of this study was to assess the effect of the exposure to fluazuron
      on the activity of common pesticide detoxification enzyme groups in the cattle
      tick (Rhipicephalus microplus). Engorged females of a susceptible strain (POA)
      and a resistant strain (Jaguar) were exposed in vitro to fluazuron and their eggs
      and larvae were used to compare the activities of the general esterases, mixed
      function oxidases (MFO) and glutathione-S-transferase (GST). The results showed
      significant elevation in MFO contents and esterases activity in the resistant
      strain when compared with the susceptible strain, in eggs and larvae
      respectively. In the POA strain, the MFO activity in eggs was down-regulated by
      fluazuron exposure. Based on these results, it can be concluded that different
      detoxification enzymes can act in distinct pathways depending on the tick's
      development stage, and may be related to fluazuron detoxification in resistant
      strains.

PMID- 28435030
TI  - The mitogen-activated protein kinase GlSlt2 regulates fungal growth, fruiting
      body development, cell wall integrity, oxidative stress and ganoderic acid
      biosynthesis in Ganoderma lucidum.
AB  - The mitogen-activated protein kinases (MAPKs) are crucial signaling instruments
      in eukaryotes that play key roles in regulating fungal growth, development, and
      secondary metabolism and in adapting to the environment. In this study, we
      characterized an Slt2-type MAPK in Ganoderma lucidum, GlSlt2, which was
      transcriptionally induced during the primordium and fruiting body stages. RNA
      interference was used to examine the function of GlSlt2. Knockdown of GlSlt2
      caused defects in growth and increased hyphal branching as well as
      hypersensitivity to cell wall-disturbing substances. Consistently, the chitin and
      beta-1,3-d-glucan contents and the expression of cell wall biosynthesis genes
      were decreased and down-regulated, respectively, in GlSlt2 knockdown strains
      compared with those in the wild type (WT). In addition, no primordium or fruiting
      body could be observed in GlSlt2 knockdown strains. Furthermore, the
      intracellular reactive oxygen species (ROS) content and ganoderic acid
      biosynthesis also decreased in GlSlt2 knockdown strains. Addition of H2O2 could
      recover the decreased ganoderic acid content in GlSlt2 knockdown strains,
      indicating that GlSlt2 might regulate ganoderic acid biosynthesis via the
      intracellular ROS level. Overall, GlSlt2 is involved in hyphal growth, fruiting
      body development, cell wall integrity, oxidative stress and ganoderic acid
      biosynthesis in G. lucidum.

PMID- 28435031
TI  - Clinical outcome associated with the use of different inhalation method with and
      without humidification in asthmatic mechanically ventilated patients.
AB  - BACKGROUND: Inhaled-medication delivered during mechanical-ventilation is
      affected by type of aerosol-generator and humidity-condition. Despite many in
      vitro studies related to aerosol-delivery to mechanically-ventilated patients,
      little has been reported on clinical effects of these variables. The aim of this
      study was to determine effect of humidification and type of aerosol-generator on
      clinical status of mechanically ventilated asthmatics. METHOD: 72 (36 females)
      asthmatic subjects receiving invasive mechanical ventilation were enrolled and
      assigned randomly to 6 treatment groups of 12 (6 females) subjects each received,
      as possible, all inhaled medication using their assigned aerosol generator and
      humidity condition during delivery. Aerosol-generators were placed immediately
      after humidifier within inspiratory limb of mechanical ventilation circuit. First
      group used vibrating-mesh-nebulizer (Aerogen Solo; VMN) with humidification;
      Second used VMN without humidification; Third used metered-dose-inhaler with
      AeroChamber Vent (MDI-AV) with humidification; Forth used MDI-AV without
      humidification; Fifth used Oxycare jet-nebulizer (JN) with humidification; Sixth
      used JN without humidification. Measured parameters included clinical-parameters
      reflected patient response (CP) and endpoint parameters e.g. length-of-stay in
      the intensive-care-unit (ICU-days) and mechanical-ventilation days (MV-days).
      RESULTS: There was no significant difference between studied subjects in the 6
      groups in baseline of CP. VMN resulted in trend to shorter ICU-days (~1.42days)
      compared to MDI-AV (p = 0.39) and relatively but not significantly shorter ICU
      days (~0.75days) compared JN. Aerosol-delivery with or without humidification did
      not have any significant effect on any of parameters studied with very light
      insignificant tendency of delivery at humid condition to decrease MV-days and ICU
      days. No significant effect was found of changing humidity during aerosol
      delivery to ventilated-patient. CONCLUSIONS: VMN to deliver aerosol in ventilated
      patient resulted in trend to decreased ICU-days compared to JN and MDI-AV.
      Aerosol-delivery with or without humidification did not have any significant
      effect on any of parameters studied. However, we recommend increasing the number
      of patients studied to corroborate this finding.

PMID- 28435032
TI  - Clinical Efficacy of 1-Year Intensive Systematic Dietary Manipulation as
      Complementary and Alternative Medicine Therapies on Female Patients With
      Interstitial Cystitis/Bladder Pain Syndrome.
AB  - OBJECTIVE: To evaluate the clinical efficacy of intensive systematic dietary
      manipulation (ISDM) for female patients with interstitial cystitis (IC)/bladder
      pain syndrome (BPS) in stable condition who were followed up in our hospital.
      MATERIALS AND METHODS: In cooperation with the nutrition control team, we created
      a basic IC/BPS diet menu for 1 month. Data regarding daily food intake and food
      related symptoms were collected by conducting a detailed interview of each
      patient, and we set meal menu to control IC/BPS symptoms and advised the patients
      to reduce the intake of specific food items to the maximum possible extent. The
      following food items were removed from or restricted in the diet of patients:
      tomatoes, tomato products, soybean, tofu product, spices, excessive potassium,
      citrus, high-acidity-inducing substances, etc. We evaluated the following factors
      3 months and 1 year after the start of the intervention: O'Leary-Sant symptom
      index, O'Leary-Sant problem index, urgency visual analogue scale score, bladder
      or pelvic pain visual analogue scale score, and numerical patient-reported
      quality of life index. RESULTS: All evaluated factors improved statistically
      significantly when the intensive group was compared with the nonintensive group
      (baseline to 3 months and 3 months to 1 year ISDM, P <.05, respectively).
      CONCLUSION: ISDM was found to alleviate the symptoms of IC/BPS in almost 3 months
      and continued clinical efficacy for at least 1 year. ISDM as one of the
      conservative treatment modality for IC/BPS should be attempted more strictly
      because of its noninvasiveness, without alterations to the other treatments.

PMID- 28435033
TI  - Could Reduced Fluid Intake Cause the Placebo Effect Seen in Overactive Bladder
      Clinical Trials? Analysis of a Large Solifenacin Integrated Database.
AB  - OBJECTIVE: To assess the hypothesis that patients receiving placebo in overactive
      bladder (OAB) trials who experience less benefit from "treatment" continue with
      behavioral modifications such as fluid restriction, whereas those on active
      treatment adopt more normal drinking patterns. This may manifest itself as a
      reduction in micturition frequency (MF). MATERIALS AND METHODS: We interrogated a
      large integrated database containing pooled patient data from 4 randomized,
      placebo-controlled phase III OAB solifenacin studies. A statistical correction
      was applied to MF to remove the influence of fluid intake. RESULTS: Pooled
      analysis using patient-level data from 3011 patients and accounting for the
      studies within the models showed that all patients voided progressively less
      total urine per 24 hours during treatment than at baseline. However, reduction in
      total urine volume voided per 24 hours was larger in patients receiving placebo
      vs those on solifenacin; with a substantial decrease in 24-hour urine output in
      the placebo group from baseline to week 4, which was not the case in active
      groups. After correcting MF for volume voided for each patient using the
      statistical correction and averaging the corrected MF per treatment arm, the
      placebo effect almost disappeared. Patients on solifenacin voided less often,
      with a statistically significant increase in volume voided each time they voided,
      vs placebo. CONCLUSION: Assuming volume voided is a good surrogate measure for
      fluid intake, this analysis shows that fluid restriction almost completely
      explains the reduction in MF in the placebo group. In contrast, patients
      receiving active treatment adopt more normal drinking patterns once they start to
      perceive improvement in their OAB symptoms.

PMID- 28435034
TI  - Cytoreductive Prostatectomy for Metastatic Prostate Cancer: First Lessons Learned
      From the Multicentric Prospective Local Treatment of Metastatic Prostate Cancer
      (LoMP) Trial.
AB  - OBJECTIVE: To prospectively evaluate patients with newly diagnosed metastatic
      prostate cancer in the context of the LoMP trial (which investigates the role of
      cytoreductive radical prostatectomy [cRP] in addition to standard of care [SoC])
      and to provide a preliminary analysis of patient's characteristics, safety of
      cRP, and early local symptoms. PATIENTS AND METHODS: cRP was performed in
      asymptomatic patients with a resectable tumor and who were fit to undergo surgery
      (group A, n = 17). Only SoC was administered to patients with metastatic prostate
      cancer ineligible or unwilling to undergo cRP (group B, n = 29). At 3 months,
      surgical complications related to cRP and local symptoms for both groups were
      evaluated. RESULTS: Median operation time, blood loss, and hospital stay for cRP
      were 215 minutes (150-290), 250 mL (100-900), and 4 days (2-7), respectively.
      Respectively 5 (29.4%) and 2 (11.8%) patients suffered grades 1 and 2
      complications within 3 months postoperatively. When compared with Group B,
      patients in group A were younger (64 vs 72 years, P = .005), had lower initial
      prostate-specific antigen (15.9 vs 156 ug/L, P = .002), and less high-volume
      metastatic disease (5.9% vs 69%, P <.001). At 3 months, 5 (29.4%) patients in
      group A reported stress urinary incontinence without any further local symptoms.
      In group B, respectively 2 (6.8%), 11 (37.9%), and 2 (6.8%) patients suffered
      urge incontinence, obstructive voiding needing medical intervention, and ureteric
      obstruction. CONCLUSION: In a group of well-selected patients, cRP is safe. These
      patients have more favorable characteristics compared with patients treated with
      only SoC. If only SoC can be offered, patients are at risk to suffer from local
      symptoms.

PMID- 28435035
TI  - The Expanding Role of Advanced Practice Providers in Urologic Procedural Care.
AB  - OBJECTIVE: To understand the role of Advanced Practice Providers (APPs) in
      urologic procedural care and its change over time. As the population ages and the
      urologic workforce struggles to meet patient access demands, the role of APPs in
      the provision of all aspects of urologic care is increasing. However, little is
      currently known about their role in procedural care. MATERIALS AND METHODS:
      Commonly performed urologic procedures were linked to Current Procedural
      Terminology (CPT) codes from 1994 to 2012. National Medicare Part B beneficiary
      claims frequency was identified using Physician Supplier Procedure Summary Master
      Files. Trends were studied for APPs, urologists, and all other providers
      nationally across numerous procedures spanning complexity, acuity, and technical
      skill set requirements. RESULTS: Between 1994 and 2012, annual Medicare claims
      for urologic procedures by APPs increased dramatically. Cystoscopy increased from
      24 to 1820 (+7483%), transrectal prostate biopsy from 17 to 834 (+4806%), complex
      Foley catheter placement from 471 to 2929 (+522%), urodynamics testing from 41 to
      9358 (+22,727%), and renal ultrasound from 18 to 4500 (+24,900%) CONCLUSION: We
      found dramatic growth in the provision of urologic procedural care by APPs over
      the past 2 decades. These data reinforce the known expansion of the APP role in
      urology and support the timeliness of ongoing collaborative multidisciplinary
      educational efforts to address unmet needs in education, training, and guideline
      formation to maximize access to urologic procedural services.

PMID- 28435036
TI  - Costunolide increases osteoblast differentiation via ATF4-dependent HO-1
      expression in C3H10T1/2 cells.
AB  - AIMS: Costunolide is a sesquiterpene lactones used in many herbal medicines, with
      well-established anti-inflammatory and anti-oxidant functions modulating
      endoplasmic reticulum (ER) stress pathways, and which promotes the expression of
      anti-oxidant genes. The aim of this study is to investigate whether costunolide
      is involved in osteoblast differentiation and, determine the mechanisms of
      differentiation in mesenchymal stem cells. MAIN METHODS: The cytotoxicity of
      costunolide was identified using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. The mRNA and protein expression levels
      of osteogenic genes were determined by RT-PCR and Western blot analysis. Alkaline
      phosphate (ALP) staining and Alizarin red S (ARS) staining were performed to
      evaluate ALP activity and matrix mineralization. Transcriptional activity was
      detected using a luciferase reporter assay. KEY FINDINGS: In this study, we
      determined that costunolide increased the expression of distal-less homeobox 5
      (Dlx5), runt-related transcription factor 2 (Runx2), ALP, and osteocalcin (OC) in
      C3H10T 1/2 cells. Furthermore, costunolide increased ALP activity and matrix
      mineralization. Interestingly, costunolide increased ER stress by Bip, activating
      transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). However, it
      did not exert effects on expression of activating transcription factor 6 (ATF6).
      ATF4 activation has a protective role in oxidative stress, and its transcription
      induces anti-oxidant genes in cells. Heme oxygenase-1 (HO-1) is a major anti
      oxidant enzyme, and is regulated by ATF4. We showed that costunolide treatment
      increased HO-1 expression. Furthermore, the HO-1 inhibitor, Sn(IV) Protoporphyrin
      IX dichloride (SnPP) was blocked costunolide-induced Runx2 expression.
      SIGNIFICANCE: Our results revealed that costunolide-induced osteoblast
      differentiation is regulated by ATF4-dependent HO-1 expression.

PMID- 28435037
TI  - Therapeutic strategies in Sickle Cell Anemia: The past present and future.
AB  - Sickle Cell Anemia (SCA) was one of the first hemoglobinopathies to be
      discovered. It is distinguished by the mutation-induced expression of a sickle
      cell variant of hemoglobin (HbS) that triggers erythrocytes to take a
      characteristic sickled conformation. The complex physiopathology of the disease
      and its associated clinical complications has initiated multi-disciplinary
      research within its field. This review attempts to lay emphasis on the evolution,
      current standpoint and future scope of therapeutic strategies in SCA.

PMID- 28435038
TI  - A convergent synthesis of novel alkyne-azide cycloaddition congeners of betulinic
      acid as potent cytotoxic agent.
AB  - In an endeavour to develop potent anti-tumor agents from betulinic acid (BA), a
      series of C-28 derived 1,2,3-triazolyl derivatives were designed and synthesized
      by employing Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition reaction. All the
      derivatives were evaluated for cytotoxic activity by MTT assay against five
      different human cancer cell lines: lung (A549), colon (HCT116), prostate (PC3),
      pancreatic (MIA PaCa-2) and breast (T47D). The data revealed that compounds 11c,
      11d, 11g, 11h and 13a possess most promising cytotoxic potential. The compound
      11h was one of the most active compounds, with IC50 values in the range of 4-6uM
      against all the five cancer cell lines. The results of this study suggested that
      derivatives with free -OH (11c, 11d and 11g) and free -COOH (11h and 13a)
      substitutions in the triazole moiety introduced at the C-28 position
      significantly improved the anti-tumor activity and may be the favourable position
      to synthesize potent anticancer leads from BA. Introduction of a non polar alkyl
      groups at C-28 position (10, 12 and 14) resulted in the significant loss of the
      activity. Further, DAPI staining, ROS generation and wound healing experiments
      revealed that compound 11h induces apoptosis in HCT-116 cells.

PMID- 28435039
TI  - Methodological considerations when calculating person-time at risk for patients
      with chronic hepatitis C undergoing antiviral treatment.

PMID- 28435040
TI  - Reply to: "Methodological considerations when calculating person-time at risk for
      patients with chronic hepatitis C undergoing antiviral treatment".

PMID- 28435041
TI  - Reply to: "Carvedilol and survival in cirrhosis with ascites: A cognitive bias?"

PMID- 28435042
TI  - Mesenchymal stromal cells for immunomodulatory cell therapy in liver
      transplantation: One step at a time.

PMID- 28435043
TI  - Carvedilol and survival in cirrhosis with ascites: A cognitive bias?

PMID- 28435044
TI  - Expertise-dependent motor somatotopy of music perception.
AB  - Precise mapping between sound and motion underlies successful communication and
      information transmission in speech and musical performance. Formation of the map
      typically undergoes plastic changes in the neuronal network between auditory and
      motor regions through training. However, to what extent the map is
      somatotopically-tuned so that auditory information can specifically modulate the
      corticospinal system responsible for the relevant motor action has not been
      elucidated. Here we addressed this issue by assessing the excitability of
      corticospinal system including the primary motor cortex (M1) innervating the hand
      intrinsic muscles by means of transcranial magnetic stimulation while trained
      pianists and musically-untrained individuals (non-musicians) were listening to
      either piano tones or noise. M1 excitability was evaluated at two anatomically
      independent muscles of the hand. The results demonstrated elevation of M1
      excitability at not all but one specific muscle while listening to piano tones in
      the pianists, but no excitability change in both of the muscles in the non
      musicians. However, listening to noise did not elicit any changes of M1
      excitability at both muscles in both the pianists and the non-musicians. These
      findings indicate that auditory information representing the trained motor action
      tunes M1 excitability in a non-uniform, somatotopically-specific manner, which is
      likely associated with multimodal experiences in musical training.

PMID- 28435045
TI  - Current direction-dependent modulation of human hand motor function by
      intermittent theta burst stimulation (iTBS).
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) with different current
      directions can activate different sets of neurons. Current direction can also
      affect the results of repetitive TMS. OBJECTIVE: To test the influence of uni
      directional intermittent theta burst stimulation (iTBS) using different current
      directions, namely posteroanterior (PA) and anteroposterior (AP), on motor
      behaviour. METHODS: In a cross-over design, PA- and AP-iTBS was applied over the
      left primary motor cortex in 19 healthy, right-handed volunteers. Performance of
      a finger-tapping task was recorded before and 0, 10, 20, and 30min after the
      iTBS. The task was conducted with the right and left hands separately at each
      time point. As a control, AP-iTBS with reduced intensity was applied to 14
      participants in a separate session (APweak condition). RESULTS: The finger
      tapping count with the left hand was decreased after PA-iTBS. Neither AP- nor
      APweak-iTBS altered the performance. CONCLUSIONS: Current direction had a
      significant impact on the after-effects of iTBS.

PMID- 28435046
TI  - A multilevel-ROI-features-based machine learning method for detection of
      morphometric biomarkers in Parkinson's disease.
AB  - Machine learning methods have been widely used in recent years for detection of
      neuroimaging biomarkers in regions of interest (ROIs) and assisting diagnosis of
      neurodegenerative diseases. The innovation of this study is to use multilevel-ROI
      features-based machine learning method to detect sensitive morphometric
      biomarkers in Parkinson's disease (PD). Specifically, the low-level ROI features
      (gray matter volume, cortical thickness, etc.) and high-level correlative
      features (connectivity between ROIs) are integrated to construct the multilevel
      ROI features. Filter- and wrapper- based feature selection method and multi
      kernel support vector machine (SVM) are used in the classification algorithm. T1
      weighted brain magnetic resonance (MR) images of 69 PD patients and 103 normal
      controls from the Parkinson's Progression Markers Initiative (PPMI) dataset are
      included in the study. The machine learning method performs well in
      classification between PD patients and normal controls with an accuracy of
      85.78%, a specificity of 87.79%, and a sensitivity of 87.64%. The most sensitive
      biomarkers between PD patients and normal controls are mainly distributed in
      frontal lobe, parental lobe, limbic lobe, temporal lobe, and central region. The
      classification performance of our method with multilevel ROI features is
      significantly improved comparing with other classification methods using single
      level features. The proposed method shows promising identification ability for
      detecting morphometric biomarkers in PD, thus confirming the potentiality of our
      method in assisting diagnosis of the disease.

PMID- 28435047
TI  - Histological and cognitive alterations in adult diabetic rats following an
      episode of juvenile diabetic ketoacidosis: Evidence of permanent cerebral injury.
AB  - Evidence suggests that diabetic ketoacidosis (DKA) may cause subtle cognitive
      alterations in children but the mechanisms are poorly understood. Acute DKA is
      associated with reactive astrogliosis and microglial activation in a rat model.
      Whether these inflammatory changes permanently alter brain histology is unknown.
      We aimed to determine whether DKA results in permanent alterations in brain
      histology and whether these changes are associated with cognitive deficits in a
      rat model. We induced diabetes in juvenile rats with streptozotocin at 4 weeks of
      age. We induced DKA in one group (n=21) at 5 weeks of age and compared this group
      to rats with diabetes without DKA episodes (n=13). Beginning at 7 weeks, rats
      underwent a series of cognitive tests to evaluate memory. At 15 weeks, rat brains
      were harvested and examined using immunohistochemistry (IHC). In tests of novel
      object recognition and social recognition, both groups performed similarly,
      however, the DKA group performed more poorly in object-place recognition tests,
      suggesting alterations in hippocampal function. IHC studies demonstrated
      increased glial fibrillary acidic protein staining intensity in the hippocampus
      of DKA rats suggesting astrogliosis, and decreased NeuN positive cell counts in
      the cortex suggesting neuron loss. These studies demonstrate that DKA results in
      permanent alterations in brain microstructure in a rat diabetes model. These
      structural changes are associated with deficits in hippocampal function.

PMID- 28435048
TI  - Morella serrata (Lam.) Killick stabilizes biomembrane and rejuvenates sexual
      competence in male Wistar rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Morella serrata L. is an indigenous medicinal
      plant to South and southern Africa with folkloric applications as aphrodisiac,
      laxative, antimicrobial, anti-inflammatory, analgesic, anti-hypertensive,
      antitussive and antidiabetic agent. AIM OF THE STUDY: This study evaluated the
      membrane stabilization and aphrodisiac potentials of its aqueous root extract in
      male Wistar rats. MATERIALS AND METHODS: While the membrane stabilization of the
      extract was investigated against bovine erythrocytes (BE), the male rats for the
      aphrodisiac study were randomized into five groups with animals in group 1 given
      sterile placebo and served as control. The rats in group 2 were treated with
      7.14mg/kg body weight of PowMaxM, while animals in groups 3, 4 and 5 were
      administered with the extract (100, 200 and 400mg/kg, respectively). All
      treatments (1mL) were done once daily for 4 weeks via oral gavaging and their
      mating behavioural, testicular, spermatogenetic and antioxidant parameters were
      evaluated. RESULTS: With the exception of the mount, intromission and post
      ejaculatory latencies that were dose-dependently reduced by the extract, other
      mating parameters were significantly improved when compared with the control.
      Similar patterns of significant improvement were also observed on the testes-body
      weight ratio, quality and viability of sperm cells as well as testicular
      concentrations of proteins, cholesterol, glycogen, testosterone, follicle
      stimulating hormone, leuitenizing hormone and glutathione (reduced) subsequent to
      treatment with the extract. Although, administration of M. serrata had no
      significant (p>0.05) effect on the testicular activity of gamma glutamyl
      transferase, those of lactate dehydrogenase, phosphatases (alkaline and acid),
      superoxide dismutase and catalase were significantly (p<0.05) induced in the
      treated animals. The extract also conferred respective significant (p<0.05)
      membrane stabilization potential of 66.02% and 60.87% on the BE against hypotonic
      solution and heat-induced hemolysis relative to 62.14% and 40.19% for ibuprofen.
      The effect elicited by the extract at the tested doses could partly be attributed
      to its antioxidant and adaptogenic constituents. CONCLUSION: The data presented
      in this study have enriched biochemical information on the root extract of M.
      serrata as a viable source of phytonutrients that could be potentially useful for
      the development of aphrodisiac drugs, and thus lending scientific credence to its
      much touted sex enhancing attributes by the Basothos of the eastern Free State
      Province of South Africa.

PMID- 28435050
TI  - The human Krebs cycle 2-oxoglutarate dehydrogenase complex creates an additional
      source of superoxide/hydrogen peroxide from 2-oxoadipate as alternative
      substrate.
AB  - Recently, we reported that the human 2-oxoglutarate dehydrogenase (hE1o)
      component of the 2-oxoglutarate dehydrogenase complex (OGDHc) could produce the
      reactive oxygen species superoxide and hydrogen peroxide (detected by chemical
      means) from its substrate 2-oxoglutarate (OG), most likely concurrently with one
      electron oxidation by dioxygen of the thiamin diphosphate (ThDP)-derived enamine
      intermediate to a C2alpha-centered radical (detected by Electron Paramagnetic
      Resonance) [Nemeria et al., 2014 [17]; Ambrus et al. 2015 [18]]. We here report
      that hE1o can also utilize the next higher homologue of OG, 2-oxoadipate (OA) as
      a substrate according to multiple criteria in our toolbox: (i) Both E1o-specific
      and overall complex activities (NADH production) were detected using OA as a
      substrate; (ii) Two post-decarboxylation intermediates were formed by hE1o from
      OA, the ThDP-enamine and the C2alpha-hydroxyalkyl-ThDP, with nearly identical
      rates for OG and OA; (iii) Both OG and OA could reductively acylate lipoyl domain
      created from dihydrolipoyl succinyltransferase (E2o); (iv) Both OG and OA gave
      alpha-ketol carboligaton products with glyoxylate, but with opposite chirality; a
      finding that could be of utility in chiral synthesis; (v) Dioxygen could oxidize
      the ThDP-derived enamine from both OG and OA, leading to ThDP-enamine radical and
      generation of superoxide and H2O2. While the observed oxidation-reduction with
      dioxygen is only a side reaction of the predominant physiological product
      glutaryl-CoA, the efficiency of superoxide/ H2O2 production was 7-times larger
      from OA than from OG, making the reaction of OGDHc with OA one of the important
      superoxide/ H2O2 producers among 2-oxo acid dehydrogenase complexes in
      mitochondria.

PMID- 28435049
TI  - Exposure of decidualized HIESC to low oxygen tension and leucine deprivation
      results in increased IGFBP-1 phosphorylation and reduced IGF-I bioactivity.
AB  - Phosphorylation of decidual IGFBP-1 enhances binding of IGF-I, limiting the
      bioavailability of this growth factor which may contribute to reduced placental
      and fetal growth. The mechanisms regulating decidual IGFBP-1 phosphorylation are
      incompletely understood. Using decidualized human immortalized endometrial
      stromal cells we tested the hypothesis that low oxygen tension or reduced leucine
      availability, believed to be common in placental insufficiency, increase the
      phosphorylation of decidual IGFBP-1. Multiple reaction monitoring-MS (MRM-MS) was
      used to quantify IGFBP-1 phosphorylation. MRM-MS validated the novel
      phosphorylation of IGFBP-1 at Ser58, however this site was unaffected by low
      oxygen tension/leucine deprivation. In contrast, significantly elevated
      phosphorylation was detected for pSer119, pSer98/pSer101 and pSer169/pSer174
      sites. Immunoblotting and dual-immunofluorescence using phosphosite-specific
      IGFBP-1 antibodies further demonstrated increased IGFBP-1 phosphorylation in
      HIESC under both treatments which concomitantly reduced IGF-I bioactivity. These
      data support the hypothesis that down regulation of IGF-I signaling links
      decidual IGFBP-1 hyperphosphorylation to restricted fetal growth in placental
      insufficiency.

PMID- 28435051
TI  - Akt1/NFkappaB signaling pathway activation by a small molecule DMA confers
      radioprotection to intestinal epithelium in xenograft model.
AB  - Normal tissue protection and recovery of radiation-induced damage are of
      paramount importance for development of radioprotector. Radioprotector which
      selectively protects normal tissues over cancerous tissues improves the
      therapeutic window of radiation therapy. In the present study, small
      bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy
      phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo
      radioprotective effects to selectively protect normal tissue over tumor with
      underlying molecular mechanism. Administration of single DMA dose prior to
      radiation has enhanced survival of Balb/c mice against sublethal and supralethal
      total body irradiation. DMA ameliorated radiation-induced damage of normal
      tissues such as hematopoietic (HP) and gastrointestinal tract (GI) system.
      Oxidative stress marker Malondialdehyde level was decreased by DMA whereas it
      maintained endogenous antioxidant status by increasing the level of reduced
      glutathione, glutathione reductase, glutathione-s-transferase, superoxide
      dismutase and total thiol content in hepatic tissue of irradiated mice.
      Mechanistic studies revealed that DMA treatment prior to radiation leads to
      Akt1/NFkappaB signaling which reduced radiation-induced genomic instability in
      normal cells. However, these pathways were not activated in tumor tissues when
      subjected to DMA treatment in similar conditions. Abrogation of Akt1 and NFkappaB
      genes resulted in no radioprotection by DMA and enhanced apoptosis against
      radiation. Plasma half-life of DMA was 3.5h and 2.65h at oral and intravenous
      dose respectively and 90% clearance was observed in 16h. In conclusion, these
      data suggests that DMA has potential to be developed as a safe radioprotective
      agent for radiation countermeasures and an adjuvant in cancer therapy.

PMID- 28435052
TI  - Neurovascular-neuroenergetic coupling axis in the brain: master regulation by
      nitric oxide and consequences in aging and neurodegeneration.
AB  - The strict energetic demands of the brain require that nutrient supply and usage
      be fine-tuned in accordance with the specific temporal and spatial patterns of
      ever-changing levels of neuronal activity. This is achieved by adjusting local
      cerebral blood flow (CBF) as a function of activity level - neurovascular
      coupling - and by changing how energy substrates are metabolized and shuttled
      amongst astrocytes and neurons - neuroenergetic coupling. Both activity-dependent
      increase of CBF and O2 and glucose utilization by active neural cells are
      inextricably linked, establishing a functional metabolic axis in the brain, the
      neurovascular-neuroenergetic coupling axis. This axis incorporates and links
      previously independent processes that need to be coordinated in the normal brain.
      We here review evidence supporting the role of neuronal-derived nitric oxide
      (*NO) as the master regulator of this axis. Nitric oxide is produced in tight
      association with glutamatergic activation and, diffusing several cell diameters,
      may interact with different molecular targets within each cell type. Hemeproteins
      such as soluble guanylate cyclase, cytochrome c oxidase and hemoglobin, with
      which *NO reacts at relatively fast rates, are but a few of the key in
      determinants of the regulatory role of *NO in the neurovascular-neuroenergetic
      coupling axis. Accordingly, critical literature supporting this concept is
      discussed. Moreover, in view of the controversy regarding the regulation of
      catabolism of different neural cells, we further discuss key aspects of the
      pathways through which *NO specifically up-regulates glycolysis in astrocytes,
      supporting lactate shuttling to neurons for oxidative breakdown. From a
      biomedical viewpoint, derailment of neurovascular-neuroenergetic axis is
      precociously linked to aberrant brain aging, cognitive impairment and
      neurodegeneration. Thus, we summarize current knowledge of how both neurovascular
      and neuroenergetic coupling are compromised in aging, traumatic brain injury,
      epilepsy and age-associated neurodegenerative disorders such as Alzheimer's
      disease and Parkinson's disease, suggesting that a shift in cellular redox
      balance may contribute to divert *NO bioactivity from regulation to dysfunction.

PMID- 28435053
TI  - In-depth analysis of the synaptic plasma membrane proteome of small hippocampal
      slices using an integrated approach.
AB  - Comprehensive knowledge of the synaptic plasma membrane (SPM) proteome of a
      distinct brain region in a defined pathological state would greatly advance the
      understanding of the underlying biology of synaptic plasticity. The development
      of innovative approaches for studying the SPM proteome of small brain tissues is
      highly desired. This study presents a suitable protocol that integrates
      biotinylation-based affinity capture of cell surface-exposed proteins, isolation
      of synaptosomes, and biochemical extraction of SPM proteins from biotinylated
      hippocampal slices. The effectiveness of this integrated method was initially
      confirmed using immunoblot analysis of synaptic markers. Subsequently, we used
      highly sensitive mass spectrometry and streamlined bioinformatics to analyze the
      obtained SPM protein-enriched fraction. Our workflow positively identified 241
      SPM proteins comprising 85 previously reported classical proteins from the pre-
      and/or post-synaptic membrane and 156 nonclassical proteins that localized to
      both the plasma membrane and synapse, and have not been previously reported as
      SPM proteins. Further analyses revealed considerable similarities in the
      physicochemical and functional properties of these proteins. Analysis of the
      interaction network using STRING indicated that the two groups showed a
      relatively strong functional correlation. Using MCODE analysis, we observed that
      65 nonclassical SPM proteins formed 12 highly interconnected clusters with 47
      classical SPM proteins, suggesting that they were the more likely SPM candidates.
      Taken together, the results of this study provide an integrated tool for
      analyzing the SPM proteome of small brain tissues, as well as a dataset of
      putative novel SPM proteins to improve the understanding of hippocampal synaptic
      plasticity.

PMID- 28435054
TI  - Experience With a Subretinal Cell-based Therapy in Patients With Geographic
      Atrophy Secondary to Age-related Macular Degeneration.
AB  - PURPOSE: To evaluate the safety and tolerability of and clinical response to a
      single, subretinal dose of human umbilical tissue-derived cells (palucorcel [CNTO
      2476]) in the eyes of adults aged >=50 years with bilateral geographic atrophy
      (GA) secondary to age-related macular degeneration (AMD). DESIGN: Phase 1/2a,
      multicenter, open-label, dose-escalation, fellow-eye-controlled study. METHODS:
      In the phase 1 portion, eyes were assigned to receive a single, subretinal dose
      of palucorcel (ranging from 6.0 * 104 to 5.6 * 105 viable cells). In the phase 2a
      portion, eyes were assigned to one of 2 palucorcel doses (6.0 * 104 or 3.0 * 105
      cells) determined during the phase 1 portion. The intervention eye was the eye
      with worse baseline visual acuity. RESULTS: A total of 35 eligible subjects
      underwent at least a partial surgical procedure. Palucorcel was administered in
      33 eyes. Overall, 17.1% (6/35) of subjects experienced retinal detachments and
      37.1% (13/35) experienced retinal perforations. No episodes of immune rejection
      or tumor formation were observed. At 1 year, >=10- and >=15-letter gains in best
      corrected visual acuity were observed in 34.5% (10/29) and 24.1% (7/29) of eyes
      receiving palucorcel, respectively, and in 3.3% (1/30; for both) of fellow eyes.
      CONCLUSIONS: The subretinal delivery procedure in this study was associated with
      a high rate of retinal perforations (n = 13) and retinal detachments (n = 6).
      When cells were sequestered in the subretinal space, palucorcel was well
      tolerated and may be associated with improvements in visual acuity. Larger
      randomized controlled studies are required to confirm these results. Future
      studies would require a modified surgical approach.

PMID- 28435055
TI  - Cloning and characterization of a new cold-adapted and thermo-tolerant iota
      carrageenase from marine bacterium Flavobacterium sp. YS-80-122.
AB  - iota-Carrageenases play a role in marine iota-carrageenan degradation, and their
      enzymatic hydrolysates are thought to be excellent antioxidants. In this study,
      we identified a new iota-carrageenase, encoded by cgiF, in psychrophilic
      bacterium Flavobacterium sp. YS-80-122. The deduced iota-carrageenase, CgiF,
      belongs to glycoside hydrolase family 82 and shows less than 40% amino acid
      identity with characterized iota-carrageenases. The activity of recombinant CgiF
      peaked at 30 degrees C (1,207.8U/mg). Notably, CgiF is a cold-adapted iota
      carrageenase, which showed 36.5% and 57% of the maximum activity at 10 degrees C
      and 15 degrees C, respectively. In addition, it is a thermo-tolerant enzyme that
      recovered 58.2% of its initial activity after heat shock. Furthermore, although
      the activity of CgiF was enhanced by NaCl, the enzyme is active in absence of
      NaCl. This study also shows that CgiF is an endo-type iota-carrageenase that
      hydrolyzes beta-1,4-linkages of iota-carrageenan, yielding neo-iota-carratetraose
      as the main product. Its cold-adaptation, thermo-tolerance, NaCl independence and
      high neo-iota-carratetraose yield make CgiF an excellent candidate for industrial
      applications in production of iota-carrageen oligosaccharides from seaweed
      polysaccharides.

PMID- 28435056
TI  - Interfacial shear rheology of beta-lactoglobulin-Bovine submaxillary mucin layers
      adsorbed at air/water interface.
AB  - The interfacial rheological properties of solutions of beta-lactoglobulin (BLG),
      as a model food compound, mixed with bovine submaxillary mucin (BSM), a major
      salivary protein, have been investigated. Time, frequency, stress sweep and flow
      measurements have been performed at different pHs (7.4, 5.0 and 3.0), to
      investigate the air/water interfacial properties. All protein layers (BLG, BSM,
      and BLG-BSM mixtures) formed an elastic network at the air/water interface with
      low frequency dependence of the interfacial modulus. The results indicated that
      BLG moves faster as smaller molecule than mucin, and dominate the surface
      adsorption and the network formation for the BLG-BSM mixtures. Moreover, BLG-BSM
      protein mixtures exhibited interfacial properties with lower elastic and viscous
      moduli than BLG, as a result of competitive displacement of BLG proteins with
      BSMs from the interface. It is suggested that hydrophobic patches of BSM can be
      imbedded into the BLG monolayer as driven by a strong hydrophobic interaction
      with air and disrupt the cohesive assembly of BLG, whereas the hydrophilic
      (negatively charged) parts of the BSM chain are protruding from the interface
      towards the bulk water.

PMID- 28435057
TI  - Accelerated wound-healing capabilities of a dressing fabricated from silkworm
      cocoon.
AB  - Silk fibroin materials have shown some success in wound dressing applications;
      however, their use for this purpose remains limited by a complex production
      process and wasted sericin. In the present study, Bombyx mori cocoon materials
      are used because the protective function of the silkworm cocoon resembles the
      manner in which the skin protects the human body. A series of silkworm cocoon sol
      gel film (SCSF) wound dressings are prepared by immersion in a CaCl2-ethanol-H2O
      solution for different treatment times. The accelerated wound-healing
      capabilities of SCSFs are systematically evaluated. Among them, the SCSF sample
      immersed for 90min exhibits stronger biocompatibility and antibacterial
      performance compared to other SCSFs. SCSF-90 also exhibits excellent
      transparency, a high swelling ratio, and good extensibility. Furthermore, in vivo
      experiments indicate that SCSF-90 can significantly accelerate the healing rate
      of wounds in New Zealand white rabbits, compared to the standard Mepitel(r)
      dressing, and histological examinations reveal that SCSF-90 aided in the
      successful reconstruction of intact and thickened epidermis. These results
      demonstrate that the proposed approach may be utilized in the design of
      antibacterial materials with promising applications in wound dressing.

PMID- 28435058
TI  - In vitro and in vivo evaluation of gastro-retentive carvedilol loaded chitosan
      beads using GastroplusTM.
AB  - The objective of present investigation was to develop gastro-retentive controlled
      release system of carvedilol using biological macromolecule, chitosan. 32 full
      factorial design was adopted for optimization of tripolyphosphate (X1) and curing
      time (X2). Bead stability in 0.1N HCl, buoyancy duration, density, drug loading,
      dissolution efficiency and cumulative percentage release at 8th hour were
      evaluated as dependent variables. The levels of X1 and X2 of optimized
      formulation having maximum desirability was found to 2.0% w/v and 62.66min,
      respectively. The in silico predicted responses and observed response were found
      to be in good agreement (percent bias error: -13.295 to +13.269). SEM images
      showed numerous pores in the cross sectional image that renders buoyancy. AUC0
      infinity of optimized formulation was 1.47 times higher as compared to suspension
      corroborating enhanced extent of absorption. Tmax and mean residence time were
      significantly higher from optimized formulation vis a vis suspension. In silico
      study indicated maximum regional absorption from the duodenum (94.1%) followed by
      jejunum (5.6%). Wagner-Nelson and Loo-Reigelman method were the preferred
      deconvolution approach over numerical deconvolution to establish IVIVC. In
      conclusion, the study showed that gastro-retentive controlled release system
      prepared using chitosan could be a potential drug carrier of carvedilol with
      improved bioavailability.

PMID- 28435059
TI  - In vivo cancer research using aggregation-induced emission organic nanoparticles.
AB  - Exploration of a nanoplatform that benefits precise cancer diagnosis and
      treatment in vivo is particularly valuable. In recent years, aggregation-induced
      emission luminogens (AIEgens) have emerged as advanced fluorescent materials for
      the design and preparation of organic nanoparticles (NPs); they also have unique
      advantages in biomedical applications, especially in cancer diagnosis and
      theranostics. In this review, we summarize the current status of the development
      of AIEgen-based NPs for in vivo cancer research, including in vivo tumor
      diagnosis, drug delivery, and photodynamic therapy. We hope that our review will
      inspire more exciting research in cross-disciplinary fields, contributing to
      precise cancer diagnostics and therapeutics.

PMID- 28435060
TI  - The multiple therapeutic applications of miRNAs for bone regenerative medicine.
AB  - With the aging of the general population, there is an increasing need for bone
      defect repair, prompting the development of reliable alternatives to autologous
      bone grafting, without the usually associated major drawbacks (i.e., limited
      volume and severe postoperative pain). Given the crucial role that miRNAs appear
      to have in bone tissue physiopathology, exploring their potential has recently
      garnered increased interest. In this review, we first describe the involvement of
      miRNAs in bone metabolism, and then focus on their potential therapeutic
      applications (as bone biomarkers and molecular targets). We also highlight the as
      yet unsolved biological (i.e., off-target effects) and technological (i.e.,
      specific delivering) challenges associated with their use.

PMID- 28435061
TI  - Nanomedicine-mediated drug targeting of cancer stem cells.
AB  - Tumors are heterogeneous and contain a small population of cells that has a
      crucial role in tumor progression, metastasis, drug resistance, and relapse as a
      result of their self-renewal, proliferation, and differentiation properties.
      These cells are known as cancer stem cells (CSCs) and accumulating evidence
      suggests that they show significant resistance to conventional chemotherapy.
      Thus, various antitumor strategies have been developed to eliminate therapeutic
      resistant CSCs by targeting the molecular differences between CSCs and bulk
      cancer cells. Here, we highlight the use of nanomedicine-mediated dual drug
      delivery to target CSCs and bulk cancer cells simultaneously. We also summarize
      current prospects and challenges associated with this therapy.

PMID- 28435062
TI  - Recent advances in activatable fluorescence imaging probes for tumor imaging.
AB  - Fluorescence imaging is superior in sensitivity and resolution compared with
      other imaging modalities; however, its application is hindered by high background
      noise. Tissue-selective strategies, such as passive, active, and activatable
      targeting, hold great promise in accelerating clinical translation by
      significantly improving the tumor:background ratio (TBR) and, in turn, the
      sensitivity and contrast of fluorescence imaging. Compared with the 'always on'
      contrast agents, activatable probes, which remain nonfluorescent until being
      activated by tumor-specific molecular targets, further enhance TBR and at the
      same time provide additional molecular information that can be related to tumor
      staging and therapy response. In this review, we summarize recent advances in the
      development of activatable fluorescence probes and provide insights into their
      advantages and limitations when used for tumor imaging.

PMID- 28435064
TI  - WITHDRAWN: Salvianolate attenuates renal fibrosis in rat models of diabetic
      nephropathy by inhibiting inflammation and oxidative stress mechanisms.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 28435063
TI  - Regulation of Nampt expression by transcriptional coactivator NCOA6 in pancreatic
      beta-cells.
AB  - Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator and
      crucial for insulin secretion and glucose metabolism in pancreatic beta-cells.
      However, the regulatory mechanism of beta-cell function by NCOA6 is largely
      unknown. In this study, we found that the transcript levels of nicotinamide
      phosphoribosyltransferase (Nampt) were decreased in islets of NCOA6+/- mice
      compared with NCOA6+/+ mice. Moreover, NCOA6 overexpression increased the levels
      of Nampt transcripts in the mouse pancreatic beta-cell line NIT-1. Promoter
      analyses showed that transcriptional activity of the Nampt promoter was
      stimulated by cooperation of sterol regulatory element binding protein-1c (SREBP
      1c) and NCOA6. Additional studies using mutant promoters demonstrated that SREBP
      1c activates Nampt promoter through the sterol regulatory element (SRE), but not
      through the E-box. Using chromatin immunoprecipitation assay, NCOA6 was also
      shown to be directly recruited to the SRE region of the Nampt promoter.
      Furthermore, treatment with nicotinamide mononucleotide (NMN), a product of the
      Nampt reaction and a key NAD+ intermediate, ameliorates glucose-stimulated
      insulin secretion from NCOA6+/- islets. These results suggest that NCOA6
      stimulates insulin secretion, at least partially, by modulating Nampt expression
      in pancreatic beta-cells.

PMID- 28435065
TI  - Influence of ER leak on resting cytoplasmic Ca2+ and receptor-mediated Ca2+
      signalling in human macrophage.
AB  - Mechanisms controlling endoplasmic reticulum (ER) Ca2+ homeostasis are important
      regulators of resting cytoplasmic Ca2+ concentration ([Ca2+]cyto) and receptor
      mediated Ca2+ signalling. Here we investigate channels responsible for ER Ca2+
      leak in THP-1 macrophage and human primary macrophage. In the absence of
      extracellular Ca2+ we employ ionomycin action at the plasma membrane to stimulate
      ER Ca2+ leak. Under these conditions ionomycin elevates [Ca2+]cyto revealing a
      Ca2+ leak response which is abolished by thapsigargin. IP3 receptors
      (Xestospongin C, 2-APB), ryanodine receptors (dantrolene), and translocon
      (anisomycin) inhibition facilitated ER Ca2+ leak in model macrophage, with
      translocon inhibition also reducing resting [Ca2+]cyto. In primary macrophage,
      translocon inhibition blocks Ca2+ leak but does not influence resting [Ca2+]cyto.
      We identify a role for translocon-mediated ER Ca2+ leak in receptor-mediated Ca2+
      signalling in both model and primary human macrophage, whereby the Ca2+ response
      to ADP (P2Y receptor agonist) is augmented following anisomycin treatment. In
      conclusion, we demonstrate a role of ER Ca2+ leak via the translocon in
      controlling resting cytoplasmic Ca2+ in model macrophage and receptor-mediated
      Ca2+ signalling in model macrophage and primary macrophage.

PMID- 28435066
TI  - Cross-talk between sumoylation and phosphorylation in mouse spermatocytes.
AB  - The meiotic G2/M1 transition is mostly regulated by posttranslational
      modifications, however, the cross-talk between different posttranslational
      modifications is not well-understood, especially in spermatocytes. Sumoylation
      has emerged as a critical regulatory event in several developmental processes,
      including reproduction. In mouse oocytes, inhibition of sumoylation caused
      various meiotic defects and led to aneuploidy. However, the role of sumoylation
      in male reproduction has only begun to be elucidated. Given the important role of
      several SUMO targets (including kinases) in meiosis, in this study, the role of
      sumoylation was addressed by monitoring the G2/M1 transition in pachytene
      spermatocytes in vitro upon inhibition of sumoylation. Furthermore, to better
      understand the cross-talk between sumoylation and phosphorylation, the activity
      of several kinases implicated in meiotic progression was also assessed upon down
      regulation of sumoylation. The results of the analysis demonstrate that
      inhibition of sumoylation with ginkgolic acid (GA) arrests the G2/M1 transition
      in mouse spermatocytes preventing chromosome condensation and disassembling of
      the synaptonemal complex. Our results revealed that the activity of PLK1 and the
      Aurora kinases increased during the G2/M1 meiotic transition, but was negatively
      regulated by the inhibition of sumoylation. In the same experiment, the activity
      of c-Abl, the ERKs, and AKT were not affected or increased after GA treatment.
      Both the AURKs and PLK1 appear to be "at the right place, at the right time" to
      at least, in part, explain the meiotic arrest obtained in the spermatocyte
      culture.

PMID- 28435067
TI  - The mitogen-activated protein kinase kinase 9 (MKK9) modulates nitrogen
      acquisition and anthocyanin accumulation under nitrogen-limiting condition in
      Arabidopsis.
AB  - Nitrogen (N) plays important roles as both a macronutrient and signal in plant
      growth and development. However, our understanding of N signaling and/or response
      mechanisms in plants is still limited. Here, we show that the mitogen-activated
      protein kinase kinase 9 (MKK9) is involved in plant N responses in Arabidopsis by
      regulating production of anthocyanins and the ability of N acquisition under low
      N conditions. Transgenic plants that express a constitutively active version of
      MKK9 (MKK9DD) showed decreased accumulation of anthocynanins and reduced
      expression of key anthocyanin biosynthetic genes under low N condition compared
      to the plants expressing the inactive form of MKK9 (MKK9KR). The decreased
      anthocyanin accumulation could be due to the increased N level in the MKK9DD
      plants as these plants were shown to accumulate more N and have higher expression
      of N acquisition-related genes under low N condition as compared with the MKK9KR
      plants. Taken together, our results suggest that MKK9 plays a role in plant
      adaptation to low N stress by modulating both anthocyanin accumulation and N
      status.

PMID- 28435068
TI  - Metal-metal interaction mediates the iron induction of Drosophila MtnB.
AB  - Metallothionein (MT) protein families are a class of small and universal proteins
      rich in cysteine residues. They are synthesized in response to heavy metal
      stresses to sequester the toxic ions by metal-thiolate bridges. Five MT family
      members, namely MtnA, MtnB, MtnC, MtnD and MtnE, have been discovered and
      identified in Drosophila. These five isoforms of MTs are regulated by metal
      responsive transcription factor dMTF-1 and play differentiated but overlapping
      roles in detoxification of metal ions. Previous researches have shown that
      Drosophila MtnB responds to copper (Cu), cadmium (Cd) and zinc (Zn).
      Interestingly in this study we found that Drosophila MtnB expression also
      responds to elevated iron levels in the diet. Further investigations revealed
      that MtnB plays limited roles in iron detoxification, and the direct binding of
      MtnB to ferrous iron in vitro is also weak. The induction of MtnB by iron turns
      out to be mediated by iron interference of other metals, because EDTA at even a
      partial concentration of that of iron can suppress this induction. Indeed, in the
      presence of iron, zinc homeostasis is altered, as reflected by expression changes
      of zinc transporters dZIP1 and dZnT1. Thus, iron-mediated MtnB induction appears
      resulting from interrupted homeostasis of other metals such as zinc, which in
      turns induced MtnB expression. Metal-metal interaction may more widely exist than
      we expected.

PMID- 28435069
TI  - Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human
      cardiac stem cells.
AB  - Aging of cardiac stem/progenitor cells (CSCs) impairs heart regeneration and
      leads to unsatisfactory outcomes of cell-based therapies. As the precise
      mechanisms underlying CSC aging remain unclear, the use of therapeutic strategies
      for elderly patients with heart failure is severely delayed. In this study, we
      used human cardiosphere-derived cells (CDCs), a subtype of CSC found in the
      postnatal heart, to identify secreted factor(s) associated with CSC aging. Human
      CDCs were isolated from heart failure patients of various ages (2-83 years old).
      Gene expression of key soluble factors was compared between CDCs derived from
      young and elderly patients. Among these factors, SFRP1, a gene encoding a Wnt
      antagonist, was significantly up-regulated in CDCs from elderly patients (>=65
      years old). sFRP1 levels was increased significantly also in CDCs, whose
      senescent phenotype was induced by anti-cancer drug treatment. These results
      suggest the participation of sFRP1 in CSC aging. We show that the administration
      of recombinant sFRP1 induced cellular senescence in CDCs derived from young
      patients, as indicated by increased levels of markers such as p16, and a
      senescence-associated secretory phenotype. In addition, co-administration of
      recombinant sFRP1 could abrogate the accelerated CDC proliferation induced by
      Wnt3A. Taken together, our results suggest that canonical Wnt signaling and its
      antagonist, sFRP1, regulate proliferation of human CSCs. Furthermore, excess
      sFRP1 in elderly patients causes CSC aging.

PMID- 28435070
TI  - Siderophores in clinical isolates of Klebsiella pneumoniae promote ciprofloxacin
      resistance by inhibiting the oxidative stress.
AB  - To explore the relevance of and understand the potential mechanisms behind the
      production of siderophores by clinical isolates of K. pneumoniae and
      ciprofloxacin (CIP) resistance, we divided the K. pneumoniae isolates into two
      groups based on bacterial siderophores production: high siderophore-yielding
      group (39 strains) and low siderophore-yielding group (38 strains). The rate of
      CIP resistance in K. pneumoniae (27/39 = 69.23%) from the high siderophore
      yielding group was significantly higher than that (16/38 = 42.11%) in the low
      siderophore-yielding group (p < 0.05). Furthermore, we noted that bacterial
      siderophores production was positively correlating with CIP resistance as
      indicated by the minimum inhibitory concentration (MIC; p < 0.05). However,
      siderophore-related antibiotic resistance had no relationship with DNA gyrase
      GyrA mutation (p > 0.05). Siderophore-related antibiotic resistance was
      accompanied by efflux pump functions, but was not directly relevant to it.
      Furthermore, we found that the oxidative stress response was significantly lower
      in high siderophore-yielding strains compared to those isolates which had a low
      siderophores yield (12.17 vs. 30.91 of average fluorescence value; p < 0.01).
      There was a consistent inverse correlation between the production of bacterial
      siderophores and oxidative stress response (p < 0.05). Although CIP induced
      oxidative stress in both high and low siderophore-yielding strains (p < 0.01),
      oxidative stress in high siderophore-yielding strains was significantly lower
      than in low siderophore-yielding strains (p < 0.01). Our data suggest that
      siderophores of K. pneumoniae clinical isolates promote CIP resistance through
      inhibition of the bacterial oxidative stress response, indicating that reduction
      of bacterial oxidative stress could provide a new avenue for control of bacterial
      drug resistance.

PMID- 28435071
TI  - ER-alpha36 mediates estrogen-stimulated MAPK/ERK activation and regulates
      migration, invasion, proliferation in cervical cancer cells.
AB  - OBJECTIVE: Estrogen receptor alpha 36 (ER-alpha36), a truncated variant of ER
      alpha, is different from other nuclear receptors of the ER-alpha family. Previous
      findings indicate that ER-alpha36 might be involved in cell growth,
      proliferation, and differentiation in carcinomas and primarily mediates non
      genomic estrogen signaling. However, studies on ER-alpha36 and cervical cancer
      are rare. This study aimed to detect the expression of ER-alpha36 in cervical
      cancer; the role of ER-alpha36 in 17-beta-estradiol (E2)-induced invasion,
      migration and proliferation of cervical cancer; and their probable molecular
      mechanisms. METHODS: Immunohistochemistry and immunofluorescence were used to
      determine the location of ER-alpha36 in cervical cancer tissues and cervical cell
      lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish
      stable cell lines with knockdown and overexpression of ER-alpha36. Wound healing
      assay, transwell invasion assay, and EdU incorporation proliferation assay were
      performed to evaluate the migration, invasion, and proliferation ability. The
      phosphorylation levels of mitogen-activated protein kinases/extracellular signal
      regulated kinase (MAPK/ERK) signaling molecules were examined with western blot
      analysis. RESULTS: ER-alpha36 expression was detected in both cervical cell lines
      and cervical cancer tissues. Downregulation of ER-alpha36 significantly inhibited
      cell invasion, migration, and proliferation. Moreover, upregulation of ER-alpha36
      increased the invasion, migration, and proliferation ability of CaSki and HeLa
      cell lines. ER-alpha36 mediates estrogen-stimulated MAPK/ERK activation.
      CONCLUSION: ER-alpha36 is localized on the plasma membrane and cytoplasm in both
      cervical cancer tissues and cell lines. ER-alpha36 mediates estrogen-stimulated
      MAPK/ERK activation and regulates migration, invasion, proliferation in cervical
      cancer cells.

PMID- 28435072
TI  - Development of a pseudovirus based assay for measuring neutralizing antibodies
      against coxsackievirus B5.
AB  - Coxsackievirus B5 (CV-B5), an important Coxsackie B virus from genus Enteroviruse
      within the family Picornaviridae, has also been isolated from Hand, Foot, and
      Mouth Disease (HFMD) patients, and often associated with neurological
      manifestations. In this study, we found out that Coxsackievirus B3 (CV-B3)
      replicon RNA could be encapsidated with CV-B5 capsid to assemble infectious CV-B5
      pseudovirus. We then utilized this single round infection system of CV-B5 to
      develop a neutralizing antibody quantification assay. This pseudovirus
      neutralization assay showed superiority in biosafety, sensibility,
      quantitativity, efficiency and high throughput, and would facilitate the
      epidemiological studies and vaccine development of CV-B5.

PMID- 28435073
TI  - Evaluation of a rapid detection for Coxsackievirus B3 using one-step reverse
      transcription loop-mediated isothermal amplification (RT-LAMP).
AB  - Coxsackievirus B3 (CVB3) is a member of the genus Enterovirus within the family
      Picornaviridae and is an important pathogen of viral myocarditis, which accounts
      for more than 50% viral myocarditis cases. VP1 is major capsid protein that this
      region has a low homology in both amino acid and nucleotide sequences among
      Enteroviruses. Therefore we have chosen this region for designed a set of RT-LAMP
      primers for CVB3 detection. For this the total RNA was extracted from 24-h post
      infected-HeLa cells with complete cytopathic effect (CPE), and applied to a one
      step reverse transcription loop-mediated isothermal amplification reaction (RT
      LAMP) using CVB3-specific primers. The optimization of RT-LAMP reaction was
      carried out with three variables factors including MgSO4 concentration,
      temperature and time of incubation. Amplification was analyzed by using 2%
      agarose gel electrophoresis and ethidium bromide and SYBR Green staining. Our
      results were shown the ladder-like pattern of the VP1 gene amplification. The
      LAMP reaction mix was optimized and the best result observed at 4mM MgSO4 and 60
      degrees C for 90min incubation. RT-LAMP had high sensitivity and specificity for
      detection of CVB3 infection. This method can be used as a rapid and easy
      diagnostic test for detection of CVB3 in clinical laboratories.

PMID- 28435074
TI  - Ultrastructure of male accessory glands in the scorpionfly Sinopanorpa tincta
      (Navas, 1931) (Mecoptera: Panorpidae).
AB  - The ultrastructure of male reproductive accessory glands was investigated in the
      scorpionfly Sinopanorpa tincta (Navas, 1931) (Mecoptera: Panorpidae) using light
      and transmission electron microscopy. The male accessory glands comprise one pair
      of mesodermal glands (mesadenia) and six pairs of ectodermal glands (ectadenia).
      The former opens into the vasa deferentia and the latter into the ejaculatory
      sac. The mesadenia consist of a mono-layered elongated columnar epithelium, the
      cells of which are highly microvillated and extrude secretory granules by means
      of merocrine mechanisms. The epithelium of ectadenia consists of two types of
      cells: the large secretory cells and the thin duct-forming cells. These two types
      of cells that join with a cuticular duct constitute a functional glandular unit,
      corresponding to the class III glandular cell type of Noirot and Quennedey. The
      cuticular duct consists of a receiving canal and a conducting canal. The
      secretory granules were taken up by the receiving canal and then plunged into the
      lumen through the conducting canal.

PMID- 28435075
TI  - Development of oral lyophilisates containing meloxicam nanocrystals using QbD
      approach.
AB  - The aim of this study was to develop oral lyophilisates with improved meloxicam
      (MEL) dissolution, optimizing each step of the preparation by design of
      experiments. First, meloxicam nanosuspensions were prepared by high-pressure
      homogenization (HPH), using PVP, Poloxamer or PEG as stabilizers and were
      subjected to freeze-drying using mannitol as cryoprotectant. The effects of the
      stabilizers and cryoprotectant were assessed and an optimal formulation was
      generated within the Design Space where the particle sizes and the PDIs are at
      their lowest values. The optimal formulation was used at the preparation of oral
      lyophilisates. Sodium alginate (SA) and croscarmellose sodium (CCS) were tested
      as matrix forming agents and three different freezing regimes were applied. The
      formulation was optimized, choosing the polymer that yielded both high mechanical
      strength and fast MEL dissolution. Poloxamer led to particle size reduction down
      to 10.27% of the initial size, meaning 477.6+/-7.5nm, with a slight increase
      during freeze-drying process. PEG showed lower nanonizing capacity during HPH,
      but freeze-drying produced further diminution of the particle size. Since
      Poloxamer provided advanced size reduction while preserving MEL crystallinity, it
      was used for the optimized formulation containing 1% Poloxamer and 5% mannitol
      added before freeze-drying. SA showed good structural properties when compared to
      CCS and allowed fast MEL dissolution at low ratios. The optimal formulation
      contained 1.157% of SA was subjected to thermal treatment during freeze-drying.
      It disintegrated in 3.33s and released 77.14% of the MEL after 2min. The quality
      by design (QbD) approach for the development of pharmaceutical products ensured
      high quality of the dosage form and good understanding of the preparation
      process.

PMID- 28435076
TI  - Design, synthesis, biological evaluation and molecular modelling of 2-(2
      aryloxyphenyl)-1,4-dihydroisoquinolin-3(2H)-ones: A novel class of TSPO ligands
      modulating amyloid-beta-induced mPTP opening.
AB  - Translocator protein (TSPO) is involved in modulating mitochondrial permeability
      transition pore (mPTP) opening/closure leading to either apoptotic cell death via
      opening of mPTP or cell protection mediated by mPTP blocking and hence
      intercepting mPTP induced apoptosis. Herein, 2-(2-aryloxyphenyl)-1,4
      dihydroisoquinolin-3(2H)-one derivatives have been designed and synthesized as
      new modulators for amyloid-beta-induced mPTP opening. Among all, compound 7c
      remarkably enhanced mPTP opening while compound 7e showed the highest mPTP
      blocking activity. Molecular modelling study revealed different binding modes
      which might underlie the observed opposing biological activities. Both compounds
      bound to the translocator protein 18kDa (TSPO) in low micromolar range and
      elicited good profiles on CYP2D6 and CYP1A2. Taken as a whole, this report
      presents compound 7e as a hit TSPO ligand for treatment of neurodegenerative
      diseases and compound 7c as a hit TSPO ligand for promoting cell death of cells
      over-expressing TSPO.

PMID- 28435077
TI  - Improving blend content uniformity via dry particle coating of micronized drug
      powders.
AB  - Content uniformity of low dose blends with fine active pharmaceutical ingredients
      (API) is adversely impacted due to API agglomeration caused by high powder
      cohesion. Dry coating using high-intensity vibratory mixing is employed to reduce
      API cohesion and granular Bond number as well as agglomeration as predicted by
      contact models, hence improve blend content uniformity (CU). Micronized
      acetaminophen (mAPAP) (~10MUm), a model API, was dry coated with nano-silica
      R972P (20nm), and mixed with Avicel 102. The amount of silica was varied from 0
      to 2.74wt%, corresponding to theoretical surface area coverage (SAC) from 0 to
      100% respectively. Bulk density, unconfined yield strength, and dispersive
      surface energy results indicated dry coating with 0.27 to 1.0wt% silica was
      adequate for API property enhancement; further corroborated by improved CU for
      5wt% API blends. Excellent CU was achieved for 3, 5 and 10wt% API loaded blends,
      where 30min of mixing was found to be acceptable for all three. The CU with dry
      coated mAPAP was significantly lower and within the acceptable range as compared
      to control blends without silica, as well as those with silica added during
      blending. Sieving of mAPAP illustrated the reduction in mAPAP agglomeration,
      necessary for improved CU after dry coating, corroborating model based
      predictions. Compared to theoretical predictions, actual CU was higher unless API
      agglomerate size distribution obtained via sieving was taken into account.
      Overall, cohesion reduction by dry coating is shown as a promising approach for
      improving content uniformity of cohesive API blends.

PMID- 28435078
TI  - Preformulation studies of ceftriaxone for pediatric non-parenteral administration
      as an alternative to existing injectable formulations.
AB  - Ceftriaxone, a third generation cephalosporin, has a wide antibacterial spectrum
      that has good CNS penetration, which makes it potentially suitable for initial
      treatment of severe neonatal pediatric infections providing suitable formulation.
      We evaluated its physicochemical and technical characteristics to assess its
      potential for development as a non-parenteral dosage form. As ceftriaxone is
      marked only for injectable use, these data are not available. Using HPLC and Karl
      Fischer titration, sensitivity of ceftriaxone to water, feasibility and impact of
      pharmaceutical processes and compatibility with common pharmaceutical excipients
      were assessed. X-ray diffraction studies gave deeper insight into the mechanisms
      involved in degradation. Chemometrical analysis of near infrared spectra enabled
      classification of ceftriaxone powder according to exposure conditions or
      processes applied. The results showed that ceftriaxone was not highly
      hygroscopic, could be processed in all climatic zones, but should be packaged
      protected against humidity. Controlling water presence in formulation was shown
      critical, as ceftriaxone degraded in the presence of water content above 2.4%
      w/w. To improve flowability, a critical parameter for dry dosage form
      development, granulation (wet and dry techniques, providing complete drying and
      moderate force compaction respectively) was shown feasible. Compression with
      moderate forces was possible, but grinding and high compression forces
      significantly affected long term ceftriaxone stability and should be avoided.
      Based on these results, development of ceftriaxone non-parenteral solid or liquid
      non-aqueous forms appears feasible.

PMID- 28435079
TI  - Polyurethane acrylates as effective substrates for sustained in vitro culture of
      human myotubes.
AB  - : Muscular disease has debilitating effects with severe damage leading to death.
      Our knowledge of muscle biology, disease and treatment is largely derived from
      non-human cell models, even though non-human cells are known to differ from human
      cells in their biochemical responses. Attempts to develop highly sought after in
      vitro human cell models have been plagued by early cell delamination and
      difficulties in achieving human myotube culture in vitro. In this work, we
      developed polyurethane acrylate (PUA) materials to support long-term in vitro
      culture of human skeletal muscle tissue. Using a constant base with modulated
      crosslink density we were able to vary the material modulus while keeping surface
      chemistry and roughness constant. While previous studies have focused on
      materials that mimic soft muscle tissue with stiffness ca. 12kPa, we investigated
      materials with tendon-like surface moduli in the higher 150MPa to 2.4GPa range,
      which has remained unexplored. We found that PUA of an optimal modulus within
      this range can support human myoblast proliferation, terminal differentiation and
      sustenance beyond 35days, without use of any extracellular protein coating.
      Results show that PUA materials can serve as effective substrates for successful
      development of human skeletal muscle cell models and are suitable for long-term
      in vitro studies. STATEMENT OF SIGNIFICANCE: We developed polyurethane acrylates
      (PUA) to modulate the human skeletal muscle cell growth and maturation in vitro
      by controlling surface chemistry, morphology and tuning material's stiffness. PUA
      was able to maintain muscle cell viability for over a month without any
      detectable signs of material degradation. The best performing PUA prevented
      premature cell detachment from the substrate which often hampered long-term
      muscle cell studies. It also supported muscle cell maturation up to the late
      stages of differentiation. The significance of these findings lies in the
      possibility to advance studies on muscle cell biology, disease and therapy by
      using human muscle cells instead of relying on the widely used animal-based in
      vitro models.

PMID- 28435080
TI  - Investigating mechanisms of tendon damage by measuring multi-scale recovery
      following tensile loading.
AB  - : Tendon pathology is associated with damage. While tendon damage is likely
      initiated by mechanical loading, little is known about the specific etiology.
      Damage is defined as an irreversible change in the microstructure that alters the
      macroscopic mechanical parameters. In tendon, the link between mechanical loading
      and microstructural damage, resulting in macroscopic changes, is not fully
      elucidated. In addition, tendon damage at the macroscale has been proposed to
      initiate when tendon is loaded beyond a strain threshold, yet the metrics to
      define the damage threshold are not determined. We conducted multi-scale
      mechanical testing to investigate the mechanism of tendon damage by
      simultaneously quantifying macroscale mechanical and microstructural changes. At
      the microscale, we observe full recovery of the fibril strain and only partial
      recovery of the interfibrillar sliding, indicating that the damage initiates at
      the interfibrillar structures. We show that non-recoverable sliding is a
      mechanism for tendon damage and is responsible for the macroscale decreased
      linear modulus and elongated toe-region observed at the fascicle-level, and these
      macroscale properties are appropriate metrics that reflect tendon damage. We
      concluded that the inflection point of the stress-strain curve represents the
      damage threshold and, therefore, may be a useful parameter for future studies.
      Establishing the mechanism of damage at multiple length scales can improve
      prevention and rehabilitation strategies for tendon pathology. STATEMENT OF
      SIGNIFICANCE: Tendon pathology is associated with mechanically induced damage.
      Damage, as defined in engineering, is an irreversible change in microstructure
      that alters the macroscopic mechanical properties. Although microstructural
      damage and changes to macroscale mechanics are likely, this link to
      microstructural change was not yet established. We conducted multiscale
      mechanical testing to investigate the mechanism of tendon damage by
      simultaneously quantifying macroscale mechanical and microstructural changes. We
      showed that non-recoverable sliding between collagen fibrils is a mechanism for
      tendon damage. Establishing the mechanism of damage at multiple length scales can
      improve prevention and rehabilitation strategies for tendon pathology.

PMID- 28435081
TI  - A Multiple Streams analysis of the decisions to fund gender-neutral HPV
      vaccination in Canada.
AB  - In Canada, the human papillomavirus (HPV) vaccine is licensed and recommended for
      females and males. Although all Canadian jurisdictions fund school-based HPV
      vaccine programs for girls, only six jurisdictions fund school-based HPV
      vaccination for boys. The research aimed to analyze the factors that underpin
      government decisions to fund HPV vaccine for boys using a theoretical policy
      model, Kingdon's Multiple Streams framework. This approach assesses policy
      development by examining three concurrent, but independent, streams that guide
      analysis: Problem Stream, Policy Stream, and Politics Stream. Analysis from the
      Problem Stream highlights that males are affected by HPV-related diseases and are
      involved in transmitting HPV infection to their sexual partners. Policy Stream
      analysis makes clear that while the inclusion of males in HPV vaccine programs is
      suitable, equitable, and acceptable; there is debate regarding cost
      effectiveness. Politics Stream analysis identifies the perspectives of six
      different stakeholder groups and highlights the contribution of government
      officials at the provincial and territorial level. Kingdon's Multiple Streams
      framework helps clarify the opportunities and barriers for HPV vaccine policy
      change. This analysis identified that the interpretation of cost-effectiveness
      models and advocacy of stakeholders such as citizen-advocates and HPV-affected
      politicians have been particularly important in galvanizing policy change.

PMID- 28435082
TI  - Anti-mitochondrial antibodies are not a hallmark of severity in idiopathic
      inflammatory myopathies.

PMID- 28435083
TI  - Subchronic glucocorticoids, glutathione depletion and a postpartum model elevate
      monoamine oxidase a activity in the prefrontal cortex of rats.
AB  - Recent human brain imaging studies implicate dysregulation of monoamine oxidase-A
      (MAO-A), in particular in the prefrontal cortex (PFC) and anterior cingulate
      cortex (ACC), in the development of major depressive disorder (MDD). This study
      investigates the influence of four alterations underlying important pathologies
      of MDD, namely, chronic elevation of glucocorticoid levels, glutathione
      depletion, changes in female gonadal sex hormones and serotonin concentration
      fluctuation, on MAO-A and MAO-B activities in rats. Young adult rats exposed
      chronically to the synthetic glucocorticoid dexamethasone at 0, 0.05, 0.5, and
      2.0mg/kg/day (osmotic minipumps) for eight days showed significant dose-dependent
      increases in activities of MAO-A in PFC (+17%, p<0.001) and ACC (+9%, p<0.01) and
      MAO-B in PFC (+14%, p<0.001) and increased serotonin turnover in the PFC (+31%,
      p<0.01), not accounted for by dexamethasone-induced changes in serotonin levels,
      since neither serotonin depletion nor supplementation affected MAO-A activity.
      Sub-acute depletion of the major antioxidant glutathione by diethyl maleate
      (5mmol/kg, i.p.) for three days, which resulted in a 36% loss of glutathione in
      PFC (p=0.0005), modestly, but significantly, elevated activities of MAO-A in PFC
      and MAO-B in PFC, ACC and hippocampus (+6-9%, p<0.05). Changes in estrogen and
      progesterone representing pseudopregnancy were associated with significantly
      elevated MAO-A activity in the ACC day 4-7 postpartum (10-18%, p<0.05 to
      p<0.0001) but not the PFC or hippocampus. Hence, our study provides data in
      support of strategies targeting glucocorticoid and glutathione systems, as well
      as changes in female sex hormones for normalization of MAO-A activities and thus
      treatment of mood disorders.

PMID- 28435084
TI  - Optimization of behavioural tests for the prediction of outcomes in mouse models
      of focal middle cerebral artery occlusion.
AB  - Intraluminal middle cerebral artery occlusion (MCAO) is the most widely used
      model of stroke. We aimed to predict the outcome of MCAO using a combination of
      fine behavioural tests for the prediction of unsuccessful surgery in mice leading
      to no infarction, haemorrhage and unexpected death. MCAO was performed on adult
      mice under the guidance of laser-Doppler flowmetry (LDF) to warrant a decrease in
      regional cerebral blood flow (rCBF) in the MCA territory. Four outcomes of MCAO
      were defined according to histological analysis: infarction, no infarction,
      haemorrhage and unexpected death (death within 24h post-surgery). Fine
      behavioural tests including the rotarod, modified neurological severity score
      (mNSS), Clark general and Clark focal tests were performed separately at 6h, 12h
      and 24h post-stroke. A total of 94 mice were included in the analysis. The
      infarction rate associated with MCAO was 58.5% (55/94). After optimization of the
      timing and behavioural tests, we found that higher Clark focal (>17.5) or higher
      mNSS scores (>10) were markedly related to early death, whereas a lower mNSS
      score (<3.5) was indicative of a tendency to show no infarction at 6h post
      stroke. After 24h post-stroke, there was a positive correlation between the
      infarct volume and Clark focal results. Behavioural tests could help to predict
      the outcomes in the MCAO mouse model.

PMID- 28435085
TI  - Adolescent changes in hindbrain noradrenergic A2 neurons in male rats.
AB  - During adolescence, the increased susceptibility to stress-related dysfunctions
      (e.g., anxiety, drug use, obesity) may be influenced by changes in the hormonal
      stress response mediated by the hypothalamic-pituitary-adrenal (HPA) axis. We
      have previously reported that restraint stress leads to significantly prolonged
      HPA responses in pre-adolescent compared to adult rats. Further, pre-adolescent
      animals exposed to restraint show greater levels of neural activation than adults
      in the paraventricular nucleus of the hypothalamus (PVN), a key nucleus
      integrating information from brain regions that coordinate HPA responses. Here,
      we examined the potential contribution of the noradrenergic A2 region of the
      nucleus of the solitary tract (NST) as a contributor to these age-dependent
      shifts in HPA reactivity. Specifically, we used double-labeled
      immunohistochemistry for FOS and dopamine-beta-hydroxylase (DbetaH) to measure
      cellular activation and noradrenergic cells, respectively, before or after
      restraint stress in pre-adolescent (30days old) and adult (70days old) male rats.
      We also measured the density of DbetaH-immunoreactive fibers in the PVN as an
      index of noradrenergic inputs to this area. We found that pre-adolescent animals
      have a greater number of DbetaH-positive cells in the A2 region compared to
      adults, yet the number and percentage of double-labeled DbetaH/FOS cells were
      similar between these two ages. We found no differences between the ages in the
      staining intensity of DbetaH-immunoreactive fibers in the PVN. These data
      indicate there are adolescent-related changes in the number of noradrenergic
      cells in the A2 region, but no clear association between the increased stress
      reactivity prior to pubertal maturation and activation of A2 noradrenergic
      afferents to the PVN.

PMID- 28435087
TI  - The complete mitochondrial genome of Clostera anachoreta (Lepidoptera:
      Notodontidae) and phylogenetic implications for Noctuoidea species.
AB  - In this study, the complete mitochondrial genome (mitogenome) of Clostera
      anachoreta (Lepidoptera: Notodontidae) was sequenced. It comprises 15,456 base
      pairs (bp), including 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs),
      22 transfer RNAs (tRNAs) and one non-coding control region (CR), as found in
      other lepidopterans. Gene order is identical to that of typical lepidopterans.
      There are 15 intergenic spacers ranging from 2 to 49bp, and 9 overlapping regions
      ranging from 1 to 8bp, occurring throughout the genome. The CR is 347bp long. All
      PCGs are initiated by ATN codons. We found a typical gene rearrangement in C.
      anachoreta (tRNAMet-tRNAIle-tRNAGln), which is different from ancestral insects
      (tRNAIle-tRNAGln-tRNAMet). The gene rearrangement can be explained by a
      duplication/random loss model. Phylogenetic analyses indicate that C. anachoreta
      belongs to Notodontidae, and that the monophyly of Lepidopteran families is well
      supported.

PMID- 28435086
TI  - Toxigenic Clostridium difficile colonization among hospitalised adults; risk
      factors and impact on survival.
AB  - OBJECTIVES: To establish risk factors for Clostridium difficile colonization
      among hospitalized patients in England. METHODS: Patients admitted to elderly
      medicine wards at three acute hospitals in England were recruited to a
      prospective observational study. Participants were asked to provide a stool
      sample as soon as possible after enrolment and then weekly during their hospital
      stay. Samples were cultured for C. difficile before ribotyping and toxin
      detection by PCR. A multivariable logistic regression model of risk factors for
      C. difficile colonization was fitted from univariable risk factors significant at
      the p < 0.05 level. RESULTS: 410/727 participants submitted >=1 stool sample and
      40 (9.8%) carried toxigenic C. difficile in the first sample taken. Ribotype 106
      was identified three times and seven other ribotypes twice. No ribotype 027
      strains were identified. Independent predictors of colonization were previous C.
      difficile infection (OR 4.53 (95% C.I. 1.33-15.48) and malnutrition (MUST score
      >=2) (OR 3.29 (95% C.I. 1.47-7.35)). Although C. difficile colonised patients
      experienced higher 90-day mortality, colonization was not an independent risk for
      death. CONCLUSIONS: In a non-epidemic setting patients who have previously had
      CDI and have a MUST score of >=2 are at increased risk of C. difficile
      colonization and could be targeted for active surveillance to prevent C.
      difficile transmission.

PMID- 28435088
TI  - Improving prediction accuracy using decision-tree-based meta-strategy and multi
      threshold sequential-voting exemplified by miRNA target prediction.
AB  - Lots of computational predictors have been developed for fast and large-scale
      analysis of biological data. However, many of them were developed long time ago
      when training datasets or sets of input features were rather small. Consequently,
      the utility of these predictors in much large datasets, which are very common in
      nowadays, need to be examined carefully. In addition, with the rapid development
      of scientific research, the expectation on the prediction accuracy of
      computational predictors is continuously uplifting. Therefore, developing novel
      strategies to improve the prediction accuracies of computational predictors
      becomes critical. In this study, the predictive results of existing individual
      miRNA target predictors were integrated into a decision-tree to make meta
      prediction. When the multi-threshold sequential-voting technique was used, the
      prediction accuracy of the decision-tree was significantly improved by at least
      thirty percentage points compared to the individual predictors.

PMID- 28435089
TI  - Cobalt chloride induces RhoA/ROCK activation and remodeling effect in H9c2
      cardiomyoblasts: Involvement of PI3K/Akt and MAPK pathways.
AB  - Chronic heart failure is a serious complication of myocardial infarction, one of
      the major causes of death worldwide that often leads to adverse cardiac
      hypertrophy and poor prognosis. Hypoxia-induced cardiac tissue remodeling is
      considered an important underlying etiology. This study aimed to delineate the
      signaling profiles of RhoA/ROCK, PI3K/Akt, and MAPK and their involvement in
      regulation of remodeling events in cultured H9c2 cardiomyoblast cells. In
      addition to its growth-suppressive effect, the hypoxia-mimetic chemical, cobalt
      chloride (CoCl2) significantly induced RhoA kinase activation as revealed by
      increased MBS phosphorylation and ROCK1/2 expression in H9c2 cells. CoCl2
      treatment up-regulated type I collagen and MMP-9, but did not affect MMP-2,
      implicating its role in tissue remodeling. Kinetic signal profiling study showed
      that CoCl2 also elicited Smad2 hyperphosphorylation and its nuclear translocation
      in the absence of TGF-beta1. In addition, CoCl2 activated Akt-, ERK1/2-, JNK-,
      and p38 MAPK-mediated signaling pathways. Kinase inhibition experiments
      demonstrated that hydroxyfasudil, a RhoA kinase inhibitor, significantly blocked
      the CoCl2- and lysophosphatidic acid-evoked Smad2 phosphorylation and
      overexpression of type I collagen and MMP-9, and that PI3K and ERK interplayed
      with RhoA and its downstream Smad2 signaling cascade. In conclusion, this study
      demonstrated that RhoA/ROCK, PI3K/Akt, and MAPK pathways are mechanistically
      involved in the CoCl2-stimulated tissue remodeling in H9c2 cardiomyoblast cells.
      Targeting signaling mediators might be used to mitigate hypoxia-related Smad2
      phosphorylation and cardiac remodeling events in ischemic cardiomyopathy.

PMID- 28435090
TI  - Trinucleotide-repeat expanded and normal DMPK transcripts contain unusually long
      poly(A) tails despite differential nuclear residence.
AB  - In yeast and higher eukaryotes nuclear retention of transcripts may serve in
      control over RNA decay, nucleocytoplasmic transport and premature cytoplasmic
      appearance of mRNAs. Hyperadenylation of RNA is known to be associated with
      nuclear retention, but the cause-consequence relationship between
      hyperadenylation and regulation of RNA nuclear export is still unclear. We
      compared polyadenylation status between normal and expanded DMPK transcripts in
      muscle cells and tissues derived from unaffected individuals and patients with
      myotonic dystrophy type 1 (DM1). DM1 is an autosomal dominant disorder caused by
      (CTG)n repeat expansion in the DMPK gene. DM1 etiology is characterized by an
      almost complete block of nuclear export of DMPK transcripts carrying a long
      (CUG)n repeat, including aberrant sequestration of RNA-binding proteins. We show
      here by use of cell fractionation, RNA size separation and analysis of poly(A)
      tail length that a considerable fraction of transcripts from the normal DMPK
      allele is also retained in the nucleus (~30%). They carry poly(A) tails with an
      unusually broad length distribution, ranging between a few dozen to >500
      adenosine residues. Remarkably, expanded DMPK (CUG)n transcripts from the mutant
      allele, almost exclusively nuclear, carry equally long poly(A) tails. Our
      findings thus suggest that nuclear retention may be a common feature of
      regulation of DMPK RNA expression. The typical forced nuclear residence of
      expanded DMPK transcripts affects this regulation in tissues of DM1 patients, but
      not through hyperadenylation.

PMID- 28435091
TI  - Antimicrobial peptides: Role in human disease and potential as immunotherapies.
AB  - Antimicrobial peptides (AMPs) have evolved through billions of years as part of
      our innate immune system. These agents are produced by various cells throughout
      the human body and play important roles in our ability to respond to infections.
      In this review, we outline evidence linking AMP expression with a range of
      inflammatory and autoimmune human diseases. Finally, we highlight the promise of
      endogenous AMP induction for the treatment of disease (i.e., host-directed
      therapy) and briefly mention the different peptide drugs that are currently
      undergoing clinical trials.

PMID- 28435092
TI  - (-)-Terpinen-4-ol changes intracellular Ca2+ handling and induces pacing
      disturbance in rat hearts.
AB  - (-)-Terpinen-4-ol is a naturally occurring plant monoterpene and has been shown
      to have a plethora of biological activities. The objective of this study was to
      investigate the effects of (-)-terpinen-4-ol on the rat heart, a key player in
      the control and maintenance of arterial blood pressure. The effects of (-)
      terpinen-4-ol on the rat heart were investigated using isolated left atrium
      isometric force measurements, in vivo electrocardiogram (ECG) recordings, patch
      clamp technique, and confocal microscopy. It was observed that (-)-terpinen-4-ol
      reduced contraction force in an isolated left atrium at millimolar
      concentrations. Conversely, it induced a positive inotropic effect and
      extrasystoles at micromolar concentrations, suggesting that (-)-terpinen-4-ol may
      have arrhythmogenic activity on cardiac tissue. In anaesthetized animals, (-)
      terpinen-4-ol also elicited rhythm disturbance, such as supraventricular
      tachycardia and atrioventricular block. To investigate the cellular mechanism
      underlying the dual effect of (-)-terpinen-4-ol on heart muscle, experiments were
      performed on isolated ventricular cardiomyocytes to determine the effect of (-)
      terpinen-4-ol on L-type Ca2+ currents, Ca2+ sparks, and Ca2+ transients. The
      arrhythmogenic activity of (-)-terpinen-4-ol in vitro and in vivo may be
      explained by its effect on intracellular Ca2+ handling. Taken together, our data
      suggest that (-)-terpinen-4-ol has cardiac arrhythmogenic activity.

PMID- 28435093
TI  - Plaque angiogenesis and intraplaque hemorrhage in atherosclerosis.
AB  - Acute cardiovascular events, due to rupture or erosion of an atherosclerotic
      plaque, represent the major cause of morbidity and mortality in patients. Growing
      evidence suggests that plaque neovascularization is an important contributor to
      plaque growth and instability. The vessels' immaturity, with profound structural
      and functional abnormalities, leads to recurrent intraplaque hemorrhage. This
      review discusses new insights of atherosclerotic neovascularization, including
      the effects of leaky neovessels on intraplaque hemorrhage, both in experimental
      models and humans. Furthermore, modalities for in vivo imaging and therapeutic
      interventions to target plaque angiogenesis will be discussed.

PMID- 28435095
TI  - Application of advanced preclinical models and methods in anesthetic
      neurotoxicity research.
AB  - Recently, there has been increasing concern regarding the potential of
      anesthetics to disturb the long-term function of the central nervous system
      (CNS). The field of anesthesia-related toxicology, therefore, has engaged
      multiple scientific disciplines and utilized a variety of pre-clinical research
      models in an attempt to identify the basic characteristics of the anesthetic
      agents that may produce acute and/or chronic adverse effects on the CNS. This
      review discusses how the application of advanced research approaches and models,
      such as the nonhuman primate, neural stem cell-derived organotypic slice cultures
      and/or organs-on-chips systems, can serve as translational models of infantile
      anesthetic exposure. Utilization of these models may expeditiously decrease the
      uncertainty in the risk posed to children by postnatal anesthetic exposure.

PMID- 28435094
TI  - Diammonium glycyrrhizinate alleviates hepatopulmonary syndrome via restoring
      superoxide dismutase 3 activity in rats.
AB  - Hepatopulmonary syndrome (HPS) has a fatal hypoxemia from pulmonary shunts.
      Superoxide dismutase 3 (SOD3) deficiency involves in this pathogenesis. The
      purpose of this study was to investigate the underlying mechanisms of diammonium
      glycyrrhizinate (DG) on HPS via SOD3. Carbon tetrachloride induced HPS rats were
      treated with captopril or DG for 56 days. Blood gas, pulmonary artery pressures,
      and histological changes were measured. Molecule dynamics of inducible (iNOS),
      endothelial (eNOS), neuronal nitric oxide synthase (nNOS) and SOD3 were assessed
      by immunohistochemistry, quantitative RT-PCR and western blot. The results showed
      that DG significantly increased partial pressure of oxygen (P<0.01), decreased
      alveolar-arterial oxygen gradient (P<0.01), and improved hypoxemia. In HPS model
      rats, anatomical pulmonary shunts were demonstrated as both constricted
      arterioles and dilated metarterioles, while physiological shunts were
      demonstrated by lowered pulmonary artery pressure in vivo. DG significantly
      reversed the vascular pathological changes. Elevated iNOS or eNOS, and decreased
      SOD3 expression in model rats indicated imbalance of nitric oxide (NO)
      bioavailability. Partial SOD3 potencies correlated with circulative events and
      NOSs, indicating that restorable SOD3 regulated arteriole constriction and
      metarteriole dilatation. DG reduced iNOS or eNOS, increased SOD3 expression,
      especially significantly increased the partial SOD3 located in pulmonary arteries
      (P<0.05), arterioles (P<0.05) and alveolus (P<0.05). These results suggested that
      DG relieved HPS shunts and limited HPS pathogenesis may associate with restoring
      SOD3 activity.

PMID- 28435096
TI  - Improving automated multiple sclerosis lesion segmentation with a cascaded 3D
      convolutional neural network approach.
AB  - In this paper, we present a novel automated method for White Matter (WM) lesion
      segmentation of Multiple Sclerosis (MS) patient images. Our approach is based on
      a cascade of two 3D patch-wise convolutional neural networks (CNN). The first
      network is trained to be more sensitive revealing possible candidate lesion
      voxels while the second network is trained to reduce the number of misclassified
      voxels coming from the first network. This cascaded CNN architecture tends to
      learn well from a small (n<=35) set of labeled data of the same MRI contrast,
      which can be very interesting in practice, given the difficulty to obtain manual
      label annotations and the large amount of available unlabeled Magnetic Resonance
      Imaging (MRI) data. We evaluate the accuracy of the proposed method on the public
      MS lesion segmentation challenge MICCAI2008 dataset, comparing it with respect to
      other state-of-the-art MS lesion segmentation tools. Furthermore, the proposed
      method is also evaluated on two private MS clinical datasets, where the
      performance of our method is also compared with different recent public available
      state-of-the-art MS lesion segmentation methods. At the time of writing this
      paper, our method is the best ranked approach on the MICCAI2008 challenge,
      outperforming the rest of 60 participant methods when using all the available
      input modalities (T1-w, T2-w and FLAIR), while still in the top-rank (3rd
      position) when using only T1-w and FLAIR modalities. On clinical MS data, our
      approach exhibits a significant increase in the accuracy segmenting of WM lesions
      when compared with the rest of evaluated methods, highly correlating (r>=0.97)
      also with the expected lesion volume.

PMID- 28435097
TI  - Defining the most probable location of the parahippocampal place area using
      cortex-based alignment and cross-validation.
AB  - The parahippocampal place area (PPA) is a widely studied high-level visual region
      in the human brain involved in place and scene processing. The goal of the
      present study was to identify the most probable location of place-selective
      voxels in medial ventral temporal cortex. To achieve this goal, we first used
      cortex-based alignment (CBA) to create a probabilistic place-selective region of
      interest (ROI) from one group of 12 participants. We then tested how well this
      ROI could predict place selectivity in each hemisphere within a new group of 12
      participants. Our results reveal that a probabilistic ROI (pROI) generated from
      one group of 12 participants accurately predicts the location and functional
      selectivity in individual brains from a new group of 12 participants, despite
      between subject variability in the exact location of place-selective voxels
      relative to the folding of parahippocampal cortex. Additionally, the prediction
      accuracy of our pROI is significantly higher than that achieved by volume-based
      Talairach alignment. Comparing the location of the pROI of the PPA relative to
      published data from over 500 participants, including data from the Human
      Connectome Project, shows a striking convergence of the predicted location of the
      PPA and the cortical location of voxels exhibiting the highest place selectivity
      across studies using various methods and stimuli. Specifically, the most
      predictive anatomical location of voxels exhibiting the highest place selectivity
      in medial ventral temporal cortex is the junction of the collateral and anterior
      lingual sulci. Methodologically, we make this pROI freely available
      (vpnl.stanford.edu/PlaceSelectivity), which provides a means to accurately
      identify a functional region from anatomical MRI data when fMRI data are not
      available (for example, in patient populations). Theoretically, we consider
      different anatomical and functional factors that may contribute to the consistent
      anatomical location of place selectivity relative to the folding of high-level
      visual cortex.

PMID- 28435098
TI  - Kinetics of chitin deacetylase activation by the ionic liquid [Bmim][Br].
AB  - Chitin deacetylase is the only known enzyme that can deacetylate the N-acetyl-d
      glucosamine units in chitin and chitosan to D-glucosamine. Unfortunately, this
      enzyme, originally obtained from fungi, usually has low activity. Here, we
      present that it is possible to enhance the activity of chitin deacetylase using
      the ionic liquid [Bmim][Br]. An increase in activity of up to 160% from the basal
      chitin deacetylase activity was observed. Kinetic investigations suggest that
      [Bmim][Br] is a non-essential activator.

PMID- 28435099
TI  - A meta-analysis but not a systematic review: an evaluation of the Global BMI
      Mortality Collaboration.
AB  - Meta-analyses of individual participant data (MIPDs) offer many advantages and
      are considered the highest level of evidence. However, MIPDs can be seriously
      compromised when they are not solidly founded upon a systematic review. These
      data-intensive collaborative projects may be led by experts who already have deep
      knowledge of the literature in the field and of the results of published studies
      and how these results vary based on different analytical approaches. If
      investigators tailor the searches, eligibility criteria, and analysis plan of the
      MIPD, they run the risk of reaching foregone conclusions. We exemplify this
      potential bias in a MIPD on the association of body mass index with mortality
      conducted by a collaboration of outstanding and extremely knowledgeable
      investigators. Contrary to a previous meta-analysis of group data that used a
      systematic review approach, the MIPD did not seem to use a formal search: it
      considered 239 studies, of which the senior author was previously aware of at
      least 238, and it violated its own listed eligibility criteria to include those
      studies and exclude other studies. It also preferred an analysis plan that was
      also known to give a specific direction of effects in already published results
      of most of the included evidence. MIPDs where results of constituent studies are
      already largely known need safeguards to their validity. These may include
      careful systematic searches, adherence to the Preferred Reporting Items for
      Systematic Review and Meta-Analyses of individual participant data guidelines,
      and exploration of the robustness of results with different analyses. They should
      also avoid selective emphasis on foregone conclusions based on previously known
      results with specific analytical choices.

PMID- 28435100
TI  - Montreal Accord on Patient-Reported Outcomes (PROs) use series - Paper 5: patient
      reported outcomes can be linked to epidemiologic measures to monitor populations
      and inform public health decisions.
AB  - BACKGROUND: A comprehensive picture of population health status can be captured
      by the incorporation of patient-reported outcome measures into population health
      monitoring. OBJECTIVE: The aim of the study was to identify the current state,
      opportunities, and future research related to the utilization of patient-reported
      outcome measures for population health monitoring in Canada. DISCUSSIONS: Patient
      reported outcome measures can help to identify community health needs in public
      health topics including injury, chronic disease, and communicable disease. They
      are currently collected in major national surveys in Canada, while electronic
      medical records, personal health records, and online patient communities could
      facilitate rapid and cost-effective collection of population-based data. Their
      effective use requires well-validated measurements and consideration to the
      factors affecting validity and reproducibility and the modes of administering
      questionnaires. Methodologically, relevant public health application of patient
      reported outcome measures includes analysis assessing measurement comparability
      across sociodemographically and clinically diverse population and the influence
      of physical and social environment. Research is needed to develop and apply
      analytical methods, harmonize patient-reported outcome measures across data
      sources and health jurisdictions, and link these measures to traditional
      epidemiologic indicators. Achieving these goals will benefit from collaboration
      among governmental agencies and expert groups.

PMID- 28435101
TI  - Interaction of glucocorticoids and progesterone derivatives with human serum
      albumin.
AB  - Glucocorticoids (GCs) and progesterone derivatives (PGDs) are steroid hormones
      with well-known biological activities. Their interaction with human serum albumin
      (HSA) may control their distribution. Their binding to albumin is poorly studied
      in literature. This paper deals with the interaction of a series of GCs
      (cortisol, cortisone, prednisolone, prednisone, 6-methylprednisolone and 9
      fluorocortisol acetate) and PGDs (progesterone, hydroxylated PGDs, methylated
      PGDs and dydrogesterone) with HSA solution (pH 7.4) at molar ratios steroid to
      HSA varying from 0 to 10. Similar titrations were conducted using Trp aqueous
      solution. Fluorescence titration method and Fourier transform infrared
      spectroscopy (FTIR) are used. PGDs (except dydrogesterone), cortisone and 9
      fluorocortisol acetate affected weakly the fluorescence of Trp in buffer solution
      while they decreased in a dose-dependent manner that of HSA. Their binding
      constants to HSA were then calculated. Moreover, displacement experiment was
      performed using bilirubin as a site marker. The binding constant of bilirubin to
      albumin was determined in the absence and presence of a steroid at a molar ratio
      steroid to HSA of 1. The results indicate that the steroids bind to HSA at site I
      in a pocket different from that of bilirubin. Furthermore, the peak positions of
      amide I and amide II bands of HSA were shifted in the presence of progesterone,
      dydrogesterone and GCs. Also a variation was observed in amide I region
      indicating the formation of hydrogen bonding between albumin and steroids.

PMID- 28435102
TI  - Simultaneous Time Interleaved MultiSlice (STIMS) for Rapid Susceptibility
      Weighted acquisition.
AB  - T2* weighted 3D Gradient Echo (GRE) acquisition is the main sequence used for
      Susceptibility Weighted Imaging (SWI) and Quantitative Susceptibility Mapping
      (QSM). These applications require a long echo time (TE) to build up phase
      contrast, requiring a long repetition time (TR), and leading to excessively
      lengthy scans. The long TE acquisition creates a significant amount of unused
      time within each TR, which can be utilized for either multi-echo sampling or
      additional image encoding with the echo-shift technique. The latter leads to
      significant saving in acquisition time while retaining the desired phase and T2*
      contrast. In this work, we introduce the Simultaneous Time Interleaved MultiSlice
      (STIMS) echo-shift technique, which mitigates slab boundary artifacts by
      interleaving comb-shaped slice groups with Simultaneous MultiSlice (SMS)
      excitation. This enjoys the same SNR benefit of 3D signal averaging as previously
      introduced multi-slab version, where each slab group is sub-resolved with kz
      phase encoding. Further, we combine SMS echo-shift with Compressed Sensing (CS)
      Wave acceleration, which enhances Wave-CAIPI acquisition/reconstruction with
      random undersampling and sparsity prior. STIMS and CS-Wave combination thus
      yields up to 45-fold acceleration over conventional full encoding, allowing a
      15sec full-brain acquisition with 1.5 mm isotropic resolution at long TE of 39 ms
      at 3T. In addition to utilizing empty sequence time due to long TE, STIMS is a
      general concept that could exploit gaps due to e.g. inversion modules in
      magnetization-prepared rapid gradient-echo (MPRAGE) and fluid attenuated
      inversion recovery (FLAIR) sequences.

PMID- 28435103
TI  - Magnetization Transfer Contrast and Chemical Exchange Saturation Transfer MRI.
      Features and analysis of the field-dependent saturation spectrum.
AB  - Magnetization Transfer Contrast (MTC) and Chemical Exchange Saturation Transfer
      (CEST) experiments measure the transfer of magnetization from molecular protons
      to the solvent water protons, an effect that becomes apparent as an MRI signal
      loss ("saturation"). This allows molecular information to be accessed with the
      enhanced sensitivity of MRI. In analogy to Magnetic Resonance Spectroscopy (MRS),
      these saturation data are presented as a function of the chemical shift of
      participating proton groups, e.g. OH, NH, NH2, which is called a Z-spectrum. In
      tissue, these Z-spectra contain the convolution of multiple saturation transfer
      effects, including nuclear Overhauser enhancements (NOEs) and chemical exchange
      contributions from protons in semi-solid and mobile macromolecules or tissue
      metabolites. As a consequence, their appearance depends on the magnetic field
      strength (B0) and pulse sequence parameters such as B1 strength, pulse shape and
      length, and interpulse delay, which presents a major problem for quantification
      and reproducibility of MTC and CEST effects. The use of higher B0 can bring
      several advantages. In addition to higher detection sensitivity (signal-to-noise
      ratio, SNR), both MTC and CEST studies benefit from longer water T1 allowing the
      saturation transferred to water to be retained longer. While MTC studies are non
      specific at any field strength, CEST specificity is expected to increase at
      higher field because of a larger chemical shift dispersion of the resonances of
      interest (similar to MRS). In addition, shifting to a slower exchange regime at
      higher B0 facilitates improved detection of the guanidinium protons of creatine
      and the inherently broad resonances of the amine protons in glutamate and the
      hydroxyl protons in myoinositol, glycogen, and glucosaminoglycans. Finally, due
      to the higher mobility of the contributing protons in CEST versus MTC, many new
      pulse sequences can be designed to more specifically edit for CEST signals and to
      remove MTC contributions.

PMID- 28435106
TI  - Comparative proteome analysis of the hepatopancreas from the Pacific white shrimp
      Litopenaeus vannamei under long-term low salinity stress.
AB  - : Litopenaeus vannamei is a typical euryhaline decapod model to study the
      osmoregulation mechanism in crustaceans. The proteomic was undertaken using
      isobaric tags for relative and absolute quantification together with the reverse
      phase in high-performance liquid chromatography mass spectrometry to
      quantitatively identify the proteins differentially expressed in the
      hepatopancreas under low salinity stress (3psu) compared with the control
      salinity (25psu). 533 proteins and 84 differentially expressed proteins were
      identified including 58 proteins with the 1.2-fold cut-off value under
      chronically low salinity stress. Among these proteins, 26 were up-regulated while
      32 were down-regulated. 48 out of 58 differentially expressed proteins were
      annotated in the Uniprot database and were mapped into 38 pathways by KEGG
      analysis. These proteins were categorized into the pathways for energy
      metabolism, signaling, immunization and detoxification, lipid and protein
      metabolism. A more active glycometabolism, positive response detoxification
      pathway, immunosuppression and positive osmoregulation were identified in
      L.vannamei under low salinity stress. This study suggests that under chronically
      low salinity stress, L. vannamei showed low immunity and high demand for energy
      especially from glycometabolism. Signaling transfer related pathways, especially
      the Wnt signaling pathways were involved in the process of salinity adaption, but
      the in-depth mechanism warrants further investigation. SIGNIFICANCE: In this
      study, a comprehensive physiological response was studied using proteomics to
      reveal the underlying mechanism of adaptation to low salinity in L.vannamei,
      which was the first report on the proteomic response of crustacean to salinity
      stress. The extensive proteomic investigation on hepatopancreas under low
      salinity stress provides a new insight into the adaptive mechanism of this
      euryhaline crustacean species to low salinity.

PMID- 28435105
TI  - Organ-specific proteomics of soybean seedlings under flooding and drought
      stresses.
AB  - : Organ-specific analyses enrich the understanding of plant growth and
      development under abiotic stresses. To elucidate the cellular responses in
      soybean seedlings exposed to flooding and drought stresses, organ-specific
      analysis was performed using a gel-free/label-free proteomic technique.
      Physiological analysis indicated that enzyme activities of alcohol dehydrogenase
      and delta-1-pyrroline-5-carboxylate synthase were markedly increased in leaf and
      root of plants treated with 6days of flooding and drought stresses, respectively.
      Proteins related to photosynthesis, RNA, DNA, signaling, and the tricarboxylic
      acid cycle were predominately affected in leaf, hypocotyl, and root in response
      to flooding and drought. Notably, the tricarboxylic acid cycle was suppressed in
      leaf and root under both stresses. Moreover, 17 proteins, including beta
      glucosidase 31 and beta-amylase 5, were identified in soybean seedlings under
      both stresses. The protein abundances of beta-glucosidase 31 and beta-amylase 5
      were increased in leaf and root under both stresses. Additionally, the gene
      expression of beta-amylase 5 was upregulated in leaf exposed to the flooding and
      drought, and the expression level was highly correlated with the protein
      abundance. These results suggest that beta-amylase 5 may be involved in
      carbohydrate mobilization to provide energy to the leaf of soybean seedlings
      exposed to flooding and drought. BIOLOGICAL SIGNIFICANCE: This study examined the
      effects of flooding and drought on soybean seedlings in different organs using a
      gel-free/label-free proteomic approach. Physiological responses indicated that
      enzyme activities of alcohol dehydrogenase and delta-1-pyrroline-5-carboxylate
      synthase were increased in leaf and root of soybean seedlings exposed to flooding
      and drought for 6days. Functional analysis of acquired protein profiles exhibited
      that proteins related to photosynthesis, RNA, DNA, signaling, and the
      tricarboxylic acid cycle were predominated affected in leaf, hypocotyl, and root
      under both stresses. Moreover, the tricarboxylic acid cycle was suppressed in
      leaf and root of stressed soybean seedlings. Additionally, increased protein
      abundance of beta-amylase 5 was consistent with upregulated gene expression in
      the leaf under both stresses, suggesting that carbohydrate metabolism might be
      governed in response to flooding and drought of soybean seedlings.

PMID- 28435104
TI  - Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor
      Parkinson's disease phenotypes.
AB  - Parkinson's disease (PD) is more commonly associated with its motor symptoms and
      the related degeneration of dopamine (DA) neurons. However, it is becoming
      increasingly clear that PD patients also display a wide range of non-motor
      symptoms, including memory deficits and disruptions of their sleep-wake cycles.
      These have a large impact on their quality of life, and often precede the onset
      of motor symptoms, but their etiology is poorly understood. The fruit fly
      Drosophila has already been successfully used to model PD, and has been used
      extensively to study relevant non-motor behaviours in other contexts, but little
      attention has yet been paid to modelling non-motor symptoms of PD in this
      genetically tractable organism. We examined memory performance and circadian
      rhythms in flies with loss-of-function mutations in two PD genes: PINK1 and
      parkin. We found learning and memory abnormalities in both mutant genotypes, as
      well as a weakening of circadian rhythms that is underpinned by
      electrophysiological changes in clock neurons. Our study paves the way for
      further work that may help us understand the mechanisms underlying these
      neglected aspects of PD, thus identifying new targets for treatments to address
      these non-motor problems specifically and perhaps even to halt disease
      progression in its prodromal phase.

PMID- 28435107
TI  - Wasp venomic: Unravelling the toxins arsenal of Polybia paulista venom and its
      potential pharmaceutical applications.
AB  - Polybia paulista (Hymenoptera: Vespidae) is a neotropical social wasp from
      southeast Brazil. As most social Hymenoptera, venom from P. paulista comprises a
      complex mixture of bioactive toxins ranging from low molecular weight compounds
      to peptides and proteins. Several efforts have been made to elucidate the
      molecular composition of the P. paulista venom. Data derived from proteomic,
      peptidomic and allergomic analyses has enhanced our understanding of the whole
      envenoming process caused by the insect sting. The combined use of
      bioinformatics, -omics- and molecular biology tools have allowed the
      identification, characterization, in vitro synthesis and recombinant expression
      of several wasp venom toxins. Some of these P. paulista - derived bioactive
      compounds have been evaluated for the rational design of antivenoms and the
      improvement of allergy specific diagnosis and immunotherapy. Molecular
      characterization of crude venom extract has enabled the description and isolation
      of novel toxins with potential biotechnological applications. Here, we review the
      different approaches that have been used to unravel the venom composition of P.
      paulista. We also describe the main groups of P. paulista - venom toxins
      currently identified and analyze their potential in the development of component
      resolved diagnosis of allergy, and in the rational design of antivenoms and novel
      bioactive drugs.

PMID- 28435108
TI  - Molecular characterization and antimicrobial susceptibility of the CA-MRSA
      isolated from healthcare workers, Tehran, Iran.
AB  - INTRODUCTION: Methicillin resistant Staphylococcus aureus (MRSA) has become as a
      nosocomial pathogen worldwide. Considering the importance of MRSA typing for
      understanding the evolution and dissemination of these strains, we studied the
      molecular characteristics of MRSA colonized healthcare workers (HCWs).
      METHODOLOGY: All MRSA isolated from HCWs, were genotyped using staphylococcal
      cassette chromosome mec (SCCmec) with multiplex PCR assay, multilocus sequence
      typing (MLST) and spa typing. Then antibiotic susceptibility pattern and presence
      of pvl genes were evaluated in MRSA isolates. RESULTS: Cluster analysis by
      eBURSTv3 showed that MRSA isolates belonged to two major clonal complexes (CC);
      CC88 (ST88, ST825, ST859) and CC30 (ST39, ST2, ST24) and five singletons. The
      most prevalent SCCmec type was type IV (70.59%) followed by type V (29.41%).
      Totally 11 different spa types were discriminated among which type t186 was
      predominant. All of the MRSA tested (100%) were susceptible to teicoplanin,
      linezolid and fusidic acid. Totally 52.94% of isolates were positive for pvl
      genes. CONCLUSIONS: The ST88-MRSA-IV accounted for most colonized MRSA isolates.
      We documented a different molecular epidemiology of MRSA nasal colonization in
      hospitals under studied, due to the introduction of epidemic clones (ST88, ST39,
      ST2235, ST80, ST813, ST398, ST825, ST24, ST22, ST859 and ST2).

PMID- 28435109
TI  - Visible light inactivation of E. coli, Cytotoxicity and ROS determination of
      biochemically capped gold nanoparticles.
AB  - The formation of metal nanoparticles is one of the most vast and intensifying
      research areas in favor of prospective applications for the advancement of new
      technologies. It is a well-founded, significant feature of green chemistry that
      making marvelous interconnection between nano-biotechnology and microbial
      biotechnology. In the present research, the aqueous extract of medicinally
      important plant Coptis Chinensis (in Chinese called "gold thread") was applied
      for the synthesis of gold nanoparticles (Au-NPs). The crystalline structure,
      size, shape and dispersion of Au-NPs were confirmed by using various
      characterization techniques i.e. X-ray Diffraction (XRD), High Resolution
      Transmission Electron Microscope (HRTEM) and Energy Dispersive X-ray (EDX). Well
      dispersed face centered cubic crystalline structures were obtained in the this
      contribution. The possible phyto-chemicals involved in the reduction and
      stabilization of Au-NPs were confirmed by Fourier Transform Infrared Spectroscopy
      (FT-IR). The prepared NPs were tested against highly drug resistance bacterium
      Escherichia coli both in light and dark. The results illustrated that the
      antibacterial efficiency of photo irradiated Au-NPs was several times higher than
      in dark Au-NPs. The zone of inhibition for irradiated Au-NPs was19 +/- 0.5 mm,
      which was higher than in dark 14 +/- 0.4 mm. This high antibacterial activity of
      photo irradiated Au-NPs are due to the production of reactive oxygen species
      which is responsible for the inhibition of bacteria.

PMID- 28435110
TI  - Truth or Consequences: The Growing Trend of Publication Retraction.

PMID- 28435111
TI  - Meta-Analysis on Safety and Efficacy of Microsurgical and Radiosurgical Treatment
      of Trigeminal Neuralgia.
AB  - BACKGROUND: Classic trigeminal neuralgia is often treated pharmacologically
      first. However, microvascular decompression (MVD) or radiosurgical treatment (RS)
      can render medication unnecessary. Objective appraisals of the 2 treatment
      modalities are scarce. OBJECTIVE: To compare the evidence regarding safety and
      efficiency of MVD and RS. METHODS: We searched PubMed for studies describing pain
      control, complications, and recurrences after MVD or RS between 2005 and 2015.
      Because randomized studies are lacking, we focused the statistical analysis on
      cohort clinical trials. Differences in outcome after treatment with either MVD or
      RS were analyzed using t tests and weighted averages. PRISMA (Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses) guidelines were followed.
      RESULTS: Fifty-three studies (13,805 patients, in 11 prospective and 42
      retrospective studies) were analyzed. Initial success rates were 71.1% for RS and
      86.9% for MVD (P < 0.0001). At last follow-up (>5 years after intervention),
      success rates decreased to 63.8% for RS versus 84% for MVD (P = 0.036). Thirty
      six months after the intervention, median percentage of recurrence was 11% for
      MVD and 25% for RS (P = 0.0015). The length of recurrence-free intervals was
      similar for MVD and RS (30.45 vs. 30.55 months; P = 0.987). There was no
      significant difference between the incidence of hearing loss after MVD and RS
      (1.51% vs. 0.74%; P = 0.21). Facial dysesthesia was reported more frequently
      after radiosurgery (2.3% vs. 28.8%; P = 0.02). CONCLUSIONS: MVD is a valid first
      line treatment option for young patients free of comorbidities. First-line RS can
      be advised in patients with a higher surgical risk.

PMID- 28435112
TI  - The Development of Better Neurosurgical Care Around the World.

PMID- 28435113
TI  - Microsurgical and Endoscopic Anatomy for Intradural Temporal Bone Drilling and
      Applications of the Electromagnetic Navigation System: Various Extensions of the
      Retrosigmoid Approach.
AB  - OBJECTIVE: The use of the retrosigmoid approach has recently been expanded by
      several modifications, including the suprameatal, transmeatal, suprajugular, and
      inframeatal extensions. Intradural temporal bone drilling without damaging vital
      structures inside or beside the bone, such as the internal carotid artery and
      jugular bulb, is a key step for these extensions. This study aimed to examine the
      microsurgical and endoscopic anatomy of the extensions of the retrosigmoid
      approach and to evaluate the clinical feasibility of an electromagnetic
      navigation system during intradural temporal bone drilling. METHODS: Five
      temporal bones and 8 cadaveric cerebellopontine angles were examined to clarify
      the anatomy of retrosigmoid intradural temporal bone drilling. Twenty additional
      cerebellopontine angles were dissected in a clinical setting with an
      electromagnetic navigation system while measuring the target registration errors
      at 8 surgical landmarks on and inside the temporal bone. RESULTS: Retrosigmoid
      intradural temporal bone drilling expanded the surgical exposure to allow access
      to the petroclival and parasellar regions (suprameatal), internal acoustic meatus
      (transmeatal), upper jugular foramen (suprajugular), and petrous apex
      (inframeatal). The electromagnetic navigation continuously guided the drilling
      without line of sight limitation, and its small devices were easily manipulated
      in the deep and narrow surgical field in the posterior fossa. Mean target
      registration error was less than 0.50 mm during these procedures. CONCLUSIONS:
      The combination of endoscopic and microsurgical techniques aids in achieving
      optimal exposure for retrosigmoid intradural temporal bone drilling. The
      electromagnetic navigation system had clear advantages with acceptable accuracy
      including the usability of small devices without line of sight limitation.

PMID- 28435114
TI  - The Decussating Fibers of the Lumbar Thoracolumbar Fascia: A Landmark for
      Identifying the L5 Spinous Process?
AB  - BACKGROUND: The thoracolumbar fascia (TLF) has been well studied and is known to
      have crisscrossing fibers. Based on surgical experience, we hypothesized that the
      decussating fibers of the TLF may indicate a specific vertebral level and
      performed an anatomic study. METHODS: Twenty adult fresh frozen cadavers aged 72
      84 years at death were placed in the prone position, and the skin of the lumbar
      and upper sacrum was removed. Careful attention was given to the TLF and any
      fibers of it that grossly crossed the midline to interdigitate with its
      contralateral counterpart. Once such decussations were identified, a metal wire
      was laid on them at their center, and fluoroscopy was performed to verify the
      vertebral level. RESULTS: Decussating fibers of the TLF were found on all but 1
      specimen (95%). The central part of the decussation on the midline corresponded
      to the spinous process of L5 in 17/19 (89%) of specimens and the lower edge (L4
      L5 interspace) of the spinous process of L4 in the remaining 2 specimens (11%).
      No specimens were found to have previous surgery in the area dissected or
      congenital anomalies of the spine. CONCLUSIONS: In our cadaveric study, the
      decussating fibers of the TLF in the lumbar region helped predict the L5 spinous
      process in 89% of specimens and the L4 spinous process in 11% of specimens. This
      anatomic landmark might be used as an adjunct to palpation and intraoperative
      imaging during surgical exploration of the lower lumbar region.

PMID- 28435115
TI  - Intraoperative Eptifibatide Administration During Urgent Arterial Bypass in
      Neurosurgery.
AB  - BACKGROUND: In some cases when risk of occlusion of a blood vessel is greater
      than risk of bleeding when patients undergo urgent or unplanned bypass during
      neurosurgery, the use of eptifibatide may be an option. We describe 2 patients
      who underwent arterial bypass in whom eptifibatide was used successfully
      intraoperatively during neurosurgery for prevention of bypass occlusion. CASE
      DESCRIPTION: The first patient presented with a right middle cerebral artery
      (MCA) aneurysm with subocclusive stenosis of the M1 branch. After right-sided
      osteoplastic frontotemporal craniotomy, the MCA bifurcation was exposed with a
      bifurcational 6-mm aneurysm with a wide neck. Prebifurcation stenosis was found,
      with yellow calcification of the vessel wall, and postbifurcation calcification
      was found on the upper M2 branch. Superficial temporal artery-MCA bypass and
      occlusion of the MCA aneurysm was done. Before the bypass, continuous intravenous
      infusion of eptifibatide 1 MUg/kg/minute was administered. The patient recovered
      normally without hemorrhage or neurologic deficit. The second patient presented
      with a left-sided lateral sphenoid wing meningioma. Left-sided frontotemporal
      craniotomy was performed, and the tumor was completely removed from the arachnoid
      layer. The temporal M3 branch was invaded by the meningioma. As there was no flow
      through the invaded segment of the aforementioned artery, termino-terminal M3
      arterial anastomosis was done. Continuous intravenous infusion of eptifibatide 1
      MUg/kg/minute was administered. Indocyanine green angiography showed normal flow
      through the anastomosis, and the patient recovered normally. CONCLUSIONS: Future
      studies are needed to test the safety and potential efficacy of eptifibatide in
      intraoperative settings.

PMID- 28435116
TI  - Chiari Malformation Type 1: A Systematic Review of Natural History and
      Conservative Management.
AB  - BACKGROUND: Chiari malformation type 1 (CM-1) is a variation of hindbrain
      development that can sometimes occur in asymptomatic individuals. Conventional
      treatment is surgical decompression, but little is known about the natural
      history of patients who do not undergo surgical management. This information is
      critical to determine how these patients should be managed. We conducted a
      systematic literature review to determine the natural history of CM-1,
      particularly in patients who did not undergo surgery and in asymptomatic
      individuals, to help patients and physicians determine when surgery is likely to
      be beneficial. METHODS: The literature search was performed following Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the
      electronic databases PubMed, Scopus, Cochrane Library, and Web of Science.
      Inclusion and exclusion criteria were predefined. RESULTS: In symptomatic
      patients who did not undergo surgery, headaches and nausea often improved,
      whereas ataxia and sensory disturbance tended not to improve spontaneously. Of
      patients, 27%-47% had an improvement in symptoms after 15 months, and 37%-40%
      with cough headache and 89% with nausea who were managed nonoperatively improved
      at follow-up. Most asymptomatic individuals with CM-1 remained asymptomatic
      (93.3%) even in the presence of syringomyelia. CONCLUSIONS: The natural history
      of mild symptomatic and asymptomatic CM-1 in adults is relatively benign and
      nonprogressive; the decision to perform surgical decompression should be based on
      severity and duration of a patient's symptoms at presentation. It is reasonable
      to observe a patient with mild or asymptomatic symptoms even in the presence of
      significant tonsillar descent or syringomyelia.

PMID- 28435117
TI  - Use of Intracranial Pressure Monitoring Frequently Refutes Diagnosis of
      Idiopathic Intracranial Hypertension.
AB  - BACKGROUND: The diagnosis and management of patients with idiopathic intracranial
      hypertension (IIH) frequently relies on lumbar puncture to ascertain intracranial
      pressure (ICP). However, ICP values derived this way may be spurious owing to
      patient body habitus and behavior. We recently incorporated direct continuous ICP
      monitoring into the work-up for IIH. METHODS: Through billing records, we
      identified all patients during a 3-year period who had a diagnosis of IIH and who
      underwent ICP monitoring before shunt placement or revision. Patient demographics
      and clinical data were reviewed. RESULTS: Of 30 patients who underwent ICP
      monitoring with an intraparenchymal wire, 17 had undergone lumbar puncture within
      the previous 6 months. Results from lumbar punctures showed an elevated opening
      pressure in all 17 patients, whereas only 2 patients (12%) were found to have
      consistently elevated ICP with direct ICP monitoring. Of 15 patients being
      evaluated for shunting, 4 (27%) were found to have elevated ICP. Of the 15
      patients with existing shunts, 2 patients (13%) were found to have malfunctioning
      shunts after pressure monitoring, and 3 patients (20%) had shunts that were found
      to be unnecessary and were removed. No patient experienced any complication from
      invasive monitoring. CONCLUSIONS: Direct ICP monitoring is the gold standard for
      determining ICP and can be safely and effectively applied to the work-up and
      treatment of patients with IIH to reduce the occurrence of misdiagnosis and
      unnecessary surgery.

PMID- 28435118
TI  - Transoral Intracranial Injury via Middle Skull Base by a Blunt Chopstick in a
      Child.
AB  - BACKGROUND: Transoral penetrating injury from a blunt-tipped chopstick is unusual
      and should be promptly dealt with because it is associated with high morbidity
      and mortality. CASE DESCRIPTION: We report a case of a 2-year-old girl who
      sustained a transoral penetrating brain injury after falling onto a bamboo
      chopstick, which penetrated through the hard palate and eventually led to middle
      skull base fracture as well as temporal lobe laceration and contusion. The
      chopstick was successfully extracted via a transoral approach followed by
      administration of empirical antibiotics and anticonvulsants. The postoperative
      course was uneventful, and a 2-year follow-up evaluation revealed a favorable
      outcome. CONCLUSIONS: Preoperative and postoperative imaging and extensive
      monitoring of the patient's condition are mandatory for evaluation of possible
      development of complications. An optimal result can be obtained by a tailored
      management and treatment approach for each specific patient.

PMID- 28435119
TI  - Linear Accelerator Stereotactic Radiosurgery of Central Nervous System
      Arteriovenous Malformations: A 15-Year Analysis of Outcome-Related Factors in a
      Single Tertiary Center.
AB  - BACKGROUND: Linear accelerator stereotactic radiosurgery is one of the modalities
      available for the treatment of central nervous system arteriovenous malformations
      (AVMs). The aim of this study was to describe our 15-year experience with this
      technique in a single tertiary center and the analysis of outcome-related
      factors. METHODS: From 1998 to 2013, 195 patients were treated with linear
      accelerator-based radiosurgery; we conducted a retrospective study collecting
      patient- and AVM-related variables. Treatment outcomes were obliteration,
      posttreatment hemorrhage, symptomatic radiation-induced changes, and 3-year
      neurologic status. We also analyzed prognostic factors of each outcome and
      predictability analysis of 5 scales: Spetzler-Martin grade, Lawton-Young
      supplementary and Lawton combined scores, radiosurgery-based AVM score, Virginia
      Radiosurgery AVM Scale, and Heidelberg score. RESULTS: Overall obliteration rate
      was 81%. Nidus diameter and venous drainage were predictive of obliteration (P <
      0.05), ruptured status and previous embolization were not related to rate of
      obliteration, and low-grade AVMs had higher obliteration rates. Posttreatment
      hemorrhage incidence was 8.72%; nidus diameter was the only predictor (P = 0.05).
      Symptomatic radiation-induced changes occurred in 11.79% of patients and were
      significantly associated with unruptured status (P < 0.05). Treatment success as
      a composite measure was obtained in 70.77% of patients. Receiver operating
      characteristic curves were presented for each scoring system and outcome measure;
      best area under the curve was 0.687 for Lawton combined score in the obliteration
      outcome. CONCLUSIONS: In the long-term, linear accelerator-based radiosurgery is
      a useful, valid, effective, and safe modality for treatment of brain AVMs.

PMID- 28435120
TI  - The role of platelets in hemostasis and the effects of snake venom toxins on
      platelet function.
AB  - The human body has a set of physiological processes, known as hemostasis, which
      keeps the blood fluid and free of clots in normal vessels; in the case of
      vascular injury, this process induces the local formation of a hemostatic plug,
      preventing hemorrhage. The hemostatic system in humans presents complex
      physiological interactions that involve platelets, plasma proteins, endothelial
      and subendothelial structures. Disequilibrium in the regulatory mechanisms that
      control the growth and the size of the thrombus is one of the factors that favors
      the development of diseases related to vascular disorders such as myocardial
      infarction and stroke, which are among the leading causes of death in the western
      world. Interfering with platelet function is a strategy for the treatment of
      thrombotic diseases. Antiplatelet drugs are used mainly in cases related to
      arterial thrombosis and interfere in the formation of the platelet plug by
      different mechanisms. Aspirin (acetylsalicylic acid) is the oldest and most
      widely used antithrombotic drug. Although highly effective in most cases, aspirin
      has limitations compared to other drugs used in the treatment of homeostatic
      disorders. For this reason, research related to molecules that interfere with
      platelet aggregation are of great relevance. In this regard, snake venoms are
      known to contain a number of molecules that interfere with hemostasis, including
      platelet function. The mechanisms by which snake venom components inhibit or
      activate platelet aggregation are varied and can be used as tools for the
      diagnosis and the treatment of several hemostatic disorders. The aim of this
      review is to present the role of platelets in hemostasis and the mechanisms by
      which snake venom toxins interfere with platelet function.

PMID- 28435121
TI  - Proteome analysis of human embryonic stem cells organelles.
AB  - : As the functions of proteins are associated with their cellular localization,
      the comprehensive sub-cellular proteome knowledge of human embryonic stem cells
      (hESCs) is indispensable for ensuring a therapeutic effect. Here, we have
      utilized a sub-cellular proteomics approach to analyze the localization of
      proteins in the nucleus, mitochondria, crude membrane, cytoplasm, heavy and light
      microsomes. Out of 2002 reproducibly identified proteins, we detected 762
      proteins in a single organelle whereas 160 proteins were found in all sub
      cellular fractions. We verified the localization of identified proteins through
      databases and discussed the consistency of the obtained results. With regards to
      the ambiguity in the definition of a membrane protein, we tried to clearly define
      the plasma membrane, peripheral membrane and membrane proteins by annotation of
      these proteins in databases, along with predictions of transmembrane helices.
      Among ten enriched signaling pathways highlighted in our results, non-canonical
      Wnt signaling were analyzed in greater detail. The functions of three novel hESC
      membrane proteins (ERBB4, GGT1 and ZDHHC13) have been assessed in terms of
      pluripotency. Our report is the most comprehensive for organellar proteomics of
      hESCs. SIGNIFICANCE: Mass spectrometric identification of proteins using a
      TripleTOF 5600 from nucleus, mitochondria, crude membrane, cytoplasm, heavy and
      light microsomal fractions highlighted the significance of the non-canonical Wnt
      signaling in human embryonic stem cells.

PMID- 28435123
TI  - Is having similar eye movement patterns during face learning and recognition
      beneficial for recognition performance? Evidence from hidden Markov modeling.
AB  - The hidden Markov model (HMM)-based approach for eye movement analysis is able to
      reflect individual differences in both spatial and temporal aspects of eye
      movements. Here we used this approach to understand the relationship between eye
      movements during face learning and recognition, and its association with
      recognition performance. We discovered holistic (i.e., mainly looking at the face
      center) and analytic (i.e., specifically looking at the two eyes in addition to
      the face center) patterns during both learning and recognition. Although for both
      learning and recognition, participants who adopted analytic patterns had better
      recognition performance than those with holistic patterns, a significant positive
      correlation between the likelihood of participants' patterns being classified as
      analytic and their recognition performance was only observed during recognition.
      Significantly more participants adopted holistic patterns during learning than
      recognition. Interestingly, about 40% of the participants used different patterns
      between learning and recognition, and among them 90% switched their patterns from
      holistic at learning to analytic at recognition. In contrast to the scan path
      theory, which posits that eye movements during learning have to be recapitulated
      during recognition for the recognition to be successful, participants who used
      the same or different patterns during learning and recognition did not differ in
      recognition performance. The similarity between their learning and recognition
      eye movement patterns also did not correlate with their recognition performance.
      These findings suggested that perceptuomotor memory elicited by eye movement
      patterns during learning does not play an important role in recognition. In
      contrast, the retrieval of diagnostic information for recognition, such as the
      eyes for face recognition, is a better predictor for recognition performance.

PMID- 28435124
TI  - Action recognition is viewpoint-dependent in the visual periphery.
AB  - Recognizing actions of others across the whole visual field is required for
      social interactions. In a previous study, we have shown that recognition is very
      good even when life-size avatars who were facing the observer carried out actions
      (e.g. waving) and were presented very far away from the fovea (Fademrecht,
      Bulthoff, & de la Rosa, 2016). We explored the possibility whether this
      remarkable performance was owed to life-size avatars facing the observer, which -
      according to some social cognitive theories (e.g. Schilbach et al., 2013) - could
      potentially activate different social perceptual processes as profile facing
      avatars. Participants therefore viewed a life-size stick figure avatar that
      carried out motion-captured social actions (greeting actions: handshake, hugging,
      waving; attacking actions: slapping, punching and kicking) in frontal and profile
      view. Participants' task was to identify the actions as 'greeting' or as 'attack'
      or to assess the emotional valence of the actions. While recognition accuracy for
      frontal and profile views did not differ, reaction times were significantly
      faster in general for profile views (i.e. the moving avatar was seen profile on)
      than for frontal views (i.e. the action was directed toward the observer). Our
      results suggest that the remarkable well action recognition performance in the
      visual periphery was not owed to a more socially engaging front facing view.
      Although action recognition seems to depend on viewpoint, action recognition in
      general remains remarkable accurate even far into the visual periphery.

PMID- 28435122
TI  - Global motion perception is related to motor function in 4.5-year-old children
      born at risk of abnormal development.
AB  - Global motion perception is often used as an index of dorsal visual stream
      function in neurodevelopmental studies. However, the relationship between global
      motion perception and visuomotor control, a primary function of the dorsal
      stream, is unclear. We measured global motion perception (motion coherence
      threshold; MCT) and performance on standardized measures of motor function in 606
      4.5-year-old children born at risk of abnormal neurodevelopment. Visual acuity,
      stereoacuity and verbal IQ were also assessed. After adjustment for verbal IQ or
      both visual acuity and stereoacuity, MCT was modestly, but significantly,
      associated with all components of motor function with the exception of fine motor
      scores. In a separate analysis, stereoacuity, but not visual acuity, was
      significantly associated with both gross and fine motor scores. These results
      indicate that the development of motion perception and stereoacuity are
      associated with motor function in pre-school children.

PMID- 28435125
TI  - The blockage of ventromedial hypothalamus CRF type 2 receptors impairs escape
      responses in the elevated T-maze.
AB  - In a previous study, the administration of corticotrophin-releasing factor (CRF)
      into the dorsomedial hypothalamus (DMH), a region that modulates defensive
      reactions, was shown to facilitate elevated T-maze (ETM) avoidance responses, an
      anxiogenic-like effect. Intra-DMH administration of the CRF type 1 receptor
      (CRFR1) antagonist antalarmin induced anxiolytic-like effects and counteracted
      the anxiogenic effects of CRF. The present study further investigates the role
      played by CRF receptors of the medial hypothalamus in anxiety. For that, male
      wistar rats were treated with CRFR1 and CRFR2-modulating drugs in the DMH or VMH,
      another hypothalamic nucleus implicated with defensive and emotional behavior,
      and tested in the ETM for inhibitory avoidance and escape measurements. In
      clinical terms, these responses have been respectively related to generalized
      anxiety and panic disorder. All animals were tested in an open field, immediately
      after the ETM, for locomotor activity assessment. The results showed that intra
      VMH CRF or antalarmin did not alter ETM avoidance or escape performance. Intra
      VMH injection of the CRFR2 preferential antagonist antisauvagine-30 or of the
      selective CRFR2 antagonist astressin 2-B inhibited escape performance, a
      panicolytic-like effect, without altering avoidance reactions. The CRFR2 agonist
      urocortin-2 intra-VMH was by itself without effect but blocked the effects of
      astressin 2-B. None of the drugs administered into the DMH altered ETM
      measurements. Additionally, none of the compounds altered locomotor activity
      measurements. These results suggest that VMH CRFR2 modulate a defensive response
      associated with panic disorder and are of relevance to the better understanding
      of the neural mechanisms underlying this pathological condition.

PMID- 28435126
TI  - Impulsivity in spontaneously hypertensive rats: Within-subjects comparison of
      sensitivity to delay and to amount of reinforcement.
AB  - Previous research has shown that spontaneously hypertensive rats (SHR) display
      higher levels of impulsive choice behavior, which is accompanied by a higher
      sensitivity to the delay of reinforcement, and by a normal sensitivity to the
      amount of reinforcement. Because those results were based on three different
      samples of subjects, in the present report we evaluated these three processes in
      the same individuals. SHR and WIS rats were exposed to concurrent-chains
      schedules in which the terminal links were manipulated to assess impulsivity,
      sensitivity to delay, and sensitivity to amount. For exploring impulsivity, a
      terminal link was associated with a small reinforcer (1 pellet) delivered after a
      short delay (2s) while the other terminal link was associated with a larger
      reinforcer (4 pellets) delivered after a longer delay (28s). For assessing
      sensitivity to delay, both alternatives delivered the same amount of
      reinforcement (1 pellet) and the only difference between them was in the delay
      before reinforcement delivery (2s vs 28s). For assessing sensitivity to amount,
      both alternatives were associated with the same delay (15s), but the alternatives
      differed in the amount of reinforcement (1 vs 4 pellets). In addition to
      replicating previously observed effects within-subjects, we were interested in
      analyzing different aspects of the regularity of rats' actions in the choice
      task. The results confirmed that previous findings were not a consequence of
      between-group differences: SHR were more impulsive and more sensitive to delay,
      while their sensitivity to amount was normal. Analyses of response regularity
      indicated that SHR subjects were more periodic in their responses to levers and
      in their feeder entries, had a higher number of short-duration bouts of
      responding, and made a substantially higher number of switches between the
      alternatives. We discuss the potential implications of these findings for the
      possible behavioral mechanisms driving the increased sensitivity to delay in SHR.

PMID- 28435127
TI  - Neural impact of low-level alcohol use on response inhibition: An fMRI
      investigation in young adults.
AB  - It is widely known that alcohol consumption adversely affects human health,
      particularly in the immature developing brains of adolescents and young adults,
      which may also have a long-lasting impact on executive functioning. The present
      study investigated the neural activity of 28 young adults from the Ottawa
      Prenatal Prospective Study (OPPS) using functional magnetic resonance imaging
      (fMRI). The purpose of this study was to discover the impact of regular low-level
      alcohol consumption on response inhibition as the participants performed a Go/No
      Go task. Results indicated that, despite a lack of performance differences, young
      adults who use alcohol on a regular basis differ significantly from those who do
      not use alcohol regularly (if at all) with respect to their neural activity as
      the circuitry engaged in response inhibition is being challenged. Specifically,
      areas that showed significantly more activation in users compared to controls
      included the left hippocampus, parahippocampal gyrus, superior frontal gyrus,
      precentral gyrus, right superior parietal lobule, and the cerebellum. These
      results suggest that even in low amounts, regular consumption of alcohol may have
      a significant impact on neurophysiological functioning during response inhibition
      in the developing brain of youth.

PMID- 28435129
TI  - Laparoscopic Sacral Colpopexy: The "6-Points" Technique.
AB  - STUDY OBJECTIVE: To illustrate laparoscopic sacral colpopexy for pelvic organ
      prolapse, a new method using a simplified mesh fixation technique, with only 6
      fixing points. DESIGN: Step-by-step explanation of the surgery using video
      (educative video). The video was approved by the local institutional review
      board. SETTING: University Hospital of Strasbourg, France (Canadian Task Force
      Classification III). PATIENTS: Women with multicompartment prolapse.
      INTERVENTION: We first dissected the promontorium and vertically incise the
      posterior parietal peritoneum on the right pelvic sidewall up the pouch of
      Douglas. We then dissect the rectovaginal septum up to the anal cap, laterally
      exposing the puborectalis muscle on each side. Middle rectal vessels can be
      coagulated and cut without increasing the risk of digestive disorders (especially
      constipation), but it is preferable to conserve them if the space is sufficient
      for suture. Then, we dissect the vesicovaginal space and realized the subtotal
      hysterectomy. Finally, we realized the fastening of the anterior and posterior
      meshes. The particularity is that we performed only 6 points for fixing the
      meshes: 1 on the puborectalis muscle on each side without tension (to reduce the
      risk of mesh contracture, dyspareunia, and chronic pelvic pain), 1 for the fixing
      of the anterior mesh on the anterior vaginal wall at the level of the bladder
      neck, and 1 on each side of the cervix for the reconstitution of the pericervical
      ring gathering together the anterior mesh, the pubocervical fascia, and the
      insertion of the uterosacral ligament at the level of the cervix and the
      posterior mesh. The sixth stitch fastened 1 of 2 meshes to the anterior
      paravertebral ligament at the level of the sacral promontory. We finished with
      the peritonization. MAIN RESULTS: The duration of surgery lasts approximately 120
      minutes in well-experienced hands. Based on our experience the 6-point technique
      was relatively simple (few laparoscopic stiches) with few operative difficulties
      and was also associated with a low rate of reintervention. CONCLUSION: Surgical
      management of middle compartment prolapse could be performed quickly and
      efficiently under laparoscopy with the "6-points" technique.

PMID- 28435128
TI  - Randomized Trial on Fast Track Care in Colorectal Surgery for Deep Infiltrating
      Endometriosis.
AB  - STUDY OBJECTIVE: To study the application of a fast-track care protocol in
      colorectal surgery for deep infiltrating endometriosis. Bowel endometriosis is an
      infrequent but not rare condition that often needs intestinal surgery and imposes
      a high economic burden on society. DESIGN: Prospective randomized trial (Canadian
      Task Force classification I). SETTING: Tertiary referral center. PATIENTS: Two
      hundred twenty-seven patients with preoperative evidence of bowel endometriosis.
      INTERVENTIONS: We randomly assigned 227 patients with preoperative evidence of
      bowel endometriosis to a fast-track protocol (no preoperative bowel preparation,
      early restoration of diet, no postoperative antibiotics, and early postoperative
      mobilization) or conventional care for laparoscopic intestinal surgery.
      Randomization was obtained on a double-blind, date-based schedule, and all
      procedures were performed by a homogenous group of expert surgeons. Surgical
      outcomes and a health economic evaluation were assessed. MEASUREMENTS AND MAIN
      RESULTS: The primary outcome was hospital stay. Patient's well-being and
      intraoperative and postoperative complications up to 30 days after surgery were
      also assessed. Subsequently, direct medical costs were analyzed. Patients
      assigned to the fast-track protocol were discharged earlier (median 3 vs 7 days,
      p < .001) with no significant differences in subjective well-being (p = .55).
      Operative details, postoperative complications, and need of temporary ileostomy
      were similar (p = .89) between groups as well as readmission rates within 30 days
      (p = .69). The application of a fast-track protocol resulted in an overall
      significant reduction of costs (USD 6699 vs 8674, p < .01), and differences were
      more evident in cases of protective stoma (7652 vs 8793, p < .05) and surgery
      with postoperative complications (10 835 vs 14 005, p < .01). CONCLUSION: The
      application of a fast-track care protocol for laparoscopy in cases of pelvic and
      intestinal endometriosis does not increase the risk of complications and ensures
      a reduction of medical costs.

PMID- 28435130
TI  - Intramyometrial Injection of Vasopressin: A Novel Method for Hemostasis at
      Laparoscopic Management of Cornual Ectopic.
AB  - STUDY OBJECTIVE: Although all ectopic pregnancies are associated with risk of
      hemorrhage, cornual pregnancies are feared for catastrophic hemorrhage and
      uncontrollable bleeding. The maternal mortality rate can be as high as 2.5%,
      which is 7 times higher than the mortality rate for ectopic pregnancies in
      general. Different techniques have been used to control hemostasis, including
      purse string suture, square suture, endo-loop, electrocoagulation, and
      devascularization. Injection of vasopressin into the uterus is a simple method
      that greatly reduces the blood loss at cornuostomy. DESIGN: A step by step
      demonstration of the surgical procedure (Canadian Task Force classification III).
      SETTING: Hospital. PATIENT, INTERVENTIONS, MEASUREMENTS AND MAIN RESULTS: A 32
      year-old woman, G7P3L3A3 (Gravida 7, Para 3, Living 3, Abortion 3), with 4 months
      of amenorrhea, was diagnosed with a cornual ectopic pregnancy. She was treated
      with 200 mg mifepristone and 800 MUg misoprostol. She had undergone dilatation
      and curettage twice and was referred for persisting cornual ectopic pregnancy. At
      laparoscopy, 20 U injection vasopressin in 100 mL .9% normal saline was injected
      into the myometrium of the uterus. Incision was made over the ectopic pregnancy
      with ultrasonic energy and the ectopic pregnancy enucleated using suction
      apparatus and ultrasonic energy. Hemostasis was ensured and the bed sutured with
      barbed suture. Surgery duration was 1 hour, and blood loss was 200 mL.
      Institutional review board and ethics committee approval was obtained.
      CONCLUSION: Injection of vasopressin into the uterus significantly reduces blood
      loss, operative time, and patient morbidity and mortality at laparoscopic
      cornuostomy.

PMID- 28435131
TI  - Repression of acetaminophen-induced hepatotoxicity by a combination of celastrol
      and brilliant blue G.
AB  - The sterile inflammatory response is an eminent contributor to acetaminophen
      (APAP)-hepatotoxicity in humans. Recent advances unraveled an axial role of the
      NLRP3-inflammasome in APAP-post injury inflammation. Nevertheless, the role of
      signaling events preceded the NLRP3-inflammasome activation, like the
      transcription factor NF-kappaB and the purinergic receptor P2X7, is still unclear
      and needs further elucidation. Here, we investigated the pharmacological
      inhibition of these upstream signaling molecules by celastrol and brilliant blue
      G (BBG) (separately or simultaneously) in APAP-hepatotoxicity in mice. The
      results indicated that both celastrol and BBG pretreatments, especially when
      combined together, curbed APAP-induced hepatocellular injury (ALT, AST and LDH)
      and death (necrosis and apoptosis). The underlying mechanisms of protection of
      such combination against APAP-challenge were attributed to their efficient
      cooperation in: i) preventing the consumption of hepatic antioxidants (reduced
      glutathione and superoxide dismutase); ii) limiting the overproduction of lipid
      peroxidation aldehydes (malondialdehyde and 4-hydroxynonenal) and total
      nitrate/nitrite products; iii) attenuating the inflammatory cells accumulation in
      the liver, as evidenced by reducing the number of F4/80 positive cells/field in
      immunostaining and myeloperoxidase activity; iv) reversing the dysregulation in
      production of pro-inflammatory (TNF-alpha, IL-17A and IL-23) and anti
      inflammatory (IL-10) cytokines; and v) enhancing the reparative capacity of
      injured hepatocytes, as demonstrated by increasing the percentage of PCNA
      positive hepatocytes per field of immunostaining. In conclusion, this murine
      study elicits a potential clinical applicability and therapeutic utility of
      celastrol and BBG combination in human cases of APAP-overdose hepatotoxicity.

PMID- 28435132
TI  - Phylogenetic position of the rainbow sardine Dussumieria (Dussumieriidae) and its
      bearing on the early evolution of the Clupeoidei.
AB  - The fish family Dussumieriidae (suborder Clupeoidei), commonly called round
      herrings, is traditionally considered to be a key taxon for understanding the
      evolution of the Clupeoidei because some of its morphological characteristics
      have been interpreted as being either derived or primitive, such as the nearly
      complete absence of abdominal scutes. Recent molecule-based studies showed that
      the Dussumieriidae is likely not a monophyletic group. None of those studies,
      however, included the genus Dussumieria (rainbow sardines) which is the type
      genus of the family Dussumieriidae. Herein, we investigated the phylogenetic
      position of Dussumieria within the Clupeoidei, using a dataset of complete
      mitogenomic sequences, including five newly determined using high-throughput
      sequencing technology. In the inferred phylogenetic reconstructions, the
      Dussumieriidae was never recovered as monophyletic, and Dussumieria was not
      exclusively related to any other of the three dussumieriid genera. Although the
      position of Dussumieria is not fully resolved, this genus represents a major
      evolutionary lineage within the Clupeoidei, along with the Engraulidae,
      Pristigasteridae, Clupeinae, Etrumeus, and two unnamed clades, one containing the
      Chirocentridae and Spratelloidinae and the other containing the Ehiravinae,
      Dorosomatinae, and Alosinae. Our results allow some comments regarding the early
      evolution of the Clupeoidei. In particular, they strongly support the hypothesis
      that the W-shaped pelvic scute does not represent a good phylogenetic character
      within the Clupeoidei as either it is primitive or, alternatively, it has
      independently evolved several times.

PMID- 28435133
TI  - De novo comparative transcriptome analysis of genes involved in fruit morphology
      of pumpkin cultivars with extreme size difference and development of EST-SSR
      markers.
AB  - The genetic basis of fruit size and shape was investigated for the first time in
      Cucurbita species and genetic loci associated with fruit morphology have been
      identified. Although extensive genomic resources are available at present for
      tomato (Solanum lycopersicum), cucumber (Cucumis sativus), melon (Cucumis melo)
      and watermelon (Citrullus lanatus), genomic databases for Cucurbita species are
      limited. Recently, our group reported the generation of pumpkin (Cucurbita pepo)
      transcriptome databases from two contrasting cultivars with extreme fruit sizes.
      In the current study we used these databases to perform comparative transcriptome
      analysis in order to identify genes with potential roles in fruit morphology and
      fruit size. Differential Gene Expression (DGE) analysis between cv. 'Munchkin'
      (small-fruit) and cv. 'Big Moose' (large-fruit) revealed a variety of candidate
      genes associated with fruit morphology with significant differences in gene
      expression between the two cultivars. In addition, we have set the framework for
      generating EST-SSR markers, which discriminate different C. pepo cultivars and
      show transferability to related Cucurbitaceae species. The results of the present
      study will contribute to both further understanding the molecular mechanisms
      regulating fruit morphology and furthermore identifying the factors that
      determine fruit size. Moreover, they may lead to the development of molecular
      marker tools for selecting genotypes with desired morphological traits.

PMID- 28435134
TI  - Association of calcitonin receptor gene (CALCR) polymorphism with kidney stone
      disease in the population of West Bengal, India.
AB  - Kidney Stone Disease (KSD) is a complex urologic disorder with strong genetic
      constituent. Earlier association studies have indicated that the genetic
      polymorphisms are the potential cause of stone materialization; however
      unfortunately, the actual genetic signature is still unknown. Therefore, present
      study was aimed to investigate the potential contribution of two important
      polymorphisms of calcitonin receptor gene (CALCR): (i) rs1801197 (Leu447Pro) and
      (ii) rs1042138 (3'UTR+18C>T) in renal stone formation. Accordingly, we enrolled
      152 patients registered with calcium-rich stone in kidney (case) and 144
      corresponding age, sex and ethnicity matched healthy individuals (controls).
      Epidemiological and clinical data were recorded as well as peripheral blood
      sample was collected from each individual. Serum creatinine and urinary calcium
      level was found high in patients, compared to controls. Out of two studied
      polymorphisms, we have not found any significant association against the
      rs1042138 with KSD, nonetheless, significant high frequency (p=0.001; Odds
      ratio=1.81; 95% CI: 1.28-2.55) of risk allele T against the rs1801197 (T>C) in
      patient was noted. Moreover, significant association with KSD was noted by
      genotypic analysis of rs1801197 (Leu447Pro) in our population. Interestingly,
      male patients carrying TT genotype was found to be at high risk of stone
      formation, while no such association was observed in female patients. Altogether,
      present study indicated that the rs1042138 might not be used as a useful marker
      for susceptibility of kidney stone formation, whereas, the rs1801197 could
      definitely be considered as one of the risk factors for KSD in Indian population
      at least in West Bengal in particular.

PMID- 28435135
TI  - Noninvasive delivery of oligonucleotide by penetratin-modified polyplexes to
      inhibit protein expression of intraocular tumor.
AB  - Our present study aimed to develop an antisense oligonucleotide (ASO) delivery
      system to achieve gene silencing in intraocular tumor via topical instillation.
      ASO specific for luciferase was chosen as model drug, polyamidoamine (PG5) was
      employed to condense ASO, and penetratin (Pene) was used to enhance cellular
      uptake. Nanoscale PG5/ASO/Pene polyplex was stabilized via noncovalent bonding.
      In vitro evaluations indicated that PG5/ASO/Pene exhibited improved cell
      penetrating and gene silencing ability compared with naked ASO and PG5/ASO.
      Subcutaneous and orthotopic tumor models expressing luciferase were established
      in nude mice. After treated by PG5/ASO/Pene, immunohistochemical results of
      subcutaneous tumors showed significant inhibition of luciferase expression via
      peritumoral injection, and bioluminescence from orthotopic tumor was obviously
      weakened via topical instillation. To date, few works were successful in
      noninvasive treatment of intraocular diseases using antisense strategy, this
      penetratin-modified polyplex could be a promising vector to inhibit protein
      expression by effectively delivering ASOs into the eye.

PMID- 28435136
TI  - Chitosan enhances nanoparticle delivery from the reproductive tract to target
      draining lymphoid organs.
AB  - To prime adaptive immune responses from the female reproductive tract (FRT),
      particulate antigens must be transported to draining lymph nodes (dLNs) since
      there are no local organized lymphoid structures equivalent to those found in the
      respiratory or gastrointestinal tracts. However, little is known about how to
      safely and effectively navigate successive barriers to transport such as crossing
      the epithelium and gaining access to migratory cells and lymphatic drainage that
      provide entry into dLNs. Here, we demonstrate that intravaginal pre-treatment
      with chitosan significantly facilitates translocation of nanoparticles (NPs)
      across the multilayered vaginal epithelium to target dLNs. In addition, chitosan
      pre-treatment was found to enhance NP associations with immunogenic antigen
      presenting cells in the vaginal submucosa. These observations indicate that
      chitosan may have great potential as an adjuvant for both local and systemic
      protective immunity against viral infections in the FRT.

PMID- 28435137
TI  - Group B Streptococcus and perinatal mortality.
AB  - The World Health Organization estimates that every year, one million neonatal
      deaths occur because of neonatal infection. Furthermore, an equal number of
      stillbirths are thought to be caused by infections. Here we discuss the role of
      Streptococcus agalactiae (group B Streptococcus, GBS) in neonatal disease and
      stillbirth.

PMID- 28435139
TI  - The role of lactic acid production by probiotic Lactobacillus species in vaginal
      health.
AB  - Vaginal eubiosis is characterised by beneficial lactobacillus-dominated
      microbiota. In contrast, vaginal dysbiosis (e.g. bacterial vaginosis, BV),
      characterised by an overgrowth of multiple anaerobes, is associated with an
      increased risk of adverse urogenital and reproductive health outcomes. A major
      distinguishing feature between the vaginal environment in states of eubiosis and
      dysbiosis is a high concentration of lactic acid, produced by lactobacilli, that
      acidifies the vagina in eubiosis versus a sharp drop in lactic acid and an
      increase in pH in dysbiosis. Here we review the antimicrobial, antiviral and
      immunomodulatory properties of lactic acid and the use of lactic acid and
      lactobacilli probiotics in preventing or treating BV.

PMID- 28435140
TI  - Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril.
AB  - Literature data relevant to the decision to allow a waiver of in vivo
      bioequivalence testing for the marketing authorization of immediate-release,
      solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a
      prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting
      enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly
      soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed
      from the gastrointestinal tract into the enterocytes. Consequently, enalapril
      maleate is a Biopharmaceutics Classification System class III substance. Because
      in situ conversion of the maleate salt to the sodium salt is sometimes used in
      production of the finished drug product, not every enalapril maleate-labeled
      finished product actually contains the maleate salt. Enalapril is not considered
      to have a narrow therapeutic index. With this background, a biowaiver-based
      approval procedure for new generic products or after major revisions to existing
      products is deemed acceptable, provided the in vitro dissolution of both test and
      reference preparation is very rapid (at least 85% within 15 min at pH 1.2, 4.5,
      and 6.8). Additionally, the test and reference product must contain the identical
      active drug ingredient.

PMID- 28435141
TI  - Thermodynamic Investigation of Carbamazepine-Saccharin Co-Crystal Polymorphs.
AB  - Polymorphism in active pharmaceutical ingredients can be regarded as critical for
      the potential that crystal form can have on the quality, efficacy, and safety of
      the final drug product. The current contribution aims to characterize
      thermodynamic interrelationship of a dimorphic co-crystal, FI and FII, involving
      carbamazepine (CBZ) and saccharin (SAC) molecules. Supramolecular synthesis of
      CBZ-SAC FI and FII has been performed using thermokinetic methods and
      systematically characterized by differential scanning calorimetry, powder X-ray
      diffraction, solubility, and slurry measurements. According to the heat of fusion
      rule by Burger and Ramberger, FI (DeltaHfus = 121.1 J/g; melting point, 172.5
      degrees C) and FII (DeltaHfus = 110.3 J/g; melting point, 164.7 degrees C) are
      monotropically related. The solubility and van't Hoff plot results suggest FI
      stable and FII metastable forms. This study reveals that CBZ-SAC co-crystal
      phases, FI or FII, could be stable to heat-induced stresses; however, FII
      converts to FI during solution-mediated transformation.

PMID- 28435138
TI  - Proteomic analysis of a mosquito host cell response to persistent Wolbachia
      infection.
AB  - Wolbachia pipientis, an obligate intracellular bacterium associated with
      arthropods and filarial worms, is a target for filarial disease treatment and
      provides a gene drive agent for insect vector population suppression/replacement.
      We compared proteomes of Aedes albopictus mosquito C/wStr1 cells persistently
      infected with Wolbachia strain wStr, relative to uninfected C7-10 control cells.
      Among approximately 2500 proteins, iTRAQ data identified 815 differentially
      abundant proteins. As functional classes, energy and central intermediary
      metabolism proteins were elevated in infected cells, while suppressed proteins
      with roles in host DNA replication, transcription and translation suggested that
      Wolbachia suppresses pathways that support host cell growth and proliferation.
      Vacuolar ATPase subunits were strongly elevated, consistent with high densities
      of Wolbachia contained individually within vacuoles. Other differential level
      proteins had roles in ROS neutralization, protein modification/degradation and
      signaling, including hypothetical proteins whose functions in Wolbachia infection
      can potentially be manipulated by RNAi interference or transfection. Detection of
      flavivirus proteins supports further analysis of poorly understood, insect
      specific flaviviruses and their potential interactions with Wolbachia,
      particularly in mosquitoes transinfected with Wolbachia. This study provides a
      framework for future attempts to manipulate pathways in insect cell lines that
      favor production of Wolbachia for eventual genetic manipulation, transformation
      and transinfection of vector species.

PMID- 28435142
TI  - Clinical Drug-Drug Interaction Evaluations to Inform Drug Use and Enable Drug
      Access.
AB  - Clinical drug-drug interactions (DDIs) can occur when multiple drugs are taken by
      the same patient. Significant DDIs can result in clinical toxicity or treatment
      failure. Therefore, DDI assessment is an integral part of drug development and
      the benefit-risk assessment of new therapies. Regulatory agencies including the
      Food and Drug Administration, the European Medicines Agency, and the
      Pharmaceuticals and Medical Devices Agency of Japan have made recommendations in
      their DDI guidance documents on various methodologies (in vitro, in silico, and
      clinical) to assess DDI potential and inform patient management strategies. This
      commentary focuses on clinical DDI evaluation for the purpose of drug development
      and regulatory evaluation.

PMID- 28435143
TI  - Estimation of Interindividual Variability of Pharmacokinetics of CYP2C9
      Substrates in Humans.
AB  - The activity of metabolic enzymes varies across individuals and populations.
      Activity varies even among individuals sharing the same genotype. Genetic
      polymorphisms in CYP2C9 cause significant interindividual variability in the
      metabolism of its substrates. However, the variability of CYP2C9 intrinsic
      hepatic clearance (CLint,h,CYP2C9) among subjects of the same genotype has not
      been reported. In this study, we estimated the coefficient of variation (CV) for
      the intrinsic hepatic clearance of tolbutamide by CYP2C9 for each CYP2C9 genotype
      using previously reported area under the blood concentration curve (AUC) and oral
      clearance (CLoral) values in a Monte Carlo simulation with a dispersion model.
      The CVs for tolbutamide CLint,h,CYP2C9 were estimated to be 18.1%, 23.9%, 25.4%,
      22.3%, 13.0%, and 19.8% for CYP2C9*1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3,
      respectively. These values are smaller than those previously reported for
      CYP2D6*1/*1 (43%), CYP2C19*1/*1 (66%), and CYP3A4 (33%). These CV values were
      used to predict AUC and CLoral variability of other CYP2C9 substrates, which are
      also substrates of other CYP isoforms. Then, the estimated CVs were consistent
      with those reported in previous studies of genotyped and ungenotyped subjects.
      Our estimates of CLint,h,CYP2C9 variability together with the variabilities of
      other isoforms are useful for predicting the AUC variability of CYP2C9
      substrates.

PMID- 28435144
TI  - Effects of Stanniocalcin-1 on glucose flux in rat brown adipose tissue.
AB  - The present work assesses in vitro the role of human Stanniocalcin 1 (hSTC-1) in
      14C-glucose metabolism in brown adipose tissue (BAT) from fed rat. In the fed
      state, hSTC-1 decreases the incorporation of 14C from glucose into lipids in the
      rat BAT. The data support the hypothesis that the capacity of the glycerol-3
      phosphate (G3P)-generating pathway (glycolysis) from glucose is regulated by hSTC
      1, decreasing the adequate supply of G3P needed for fatty acid esterification and
      triacylglycerol (TG) storage in BAT. The results also suggest the effect of hSTC
      1 on de novo fatty acid synthesis from pyruvate generated by 14C-glucose in the
      glycolysis pathway. In addition, by decreasing lipogenesis, hSTC-1 increased ATP
      levels and these two factors may decrease BAT thermogenic function. The presence
      of hSTC-1 in the incubation medium did not alter 14C-glucose and 14C-1-palmitic
      acid oxidation. The uncoupling protein 1 (UCP-1) expression was not altered by
      hSTC-1 either. In conclusion, hSTC-1 is one of the hormonal factors that control
      glucose metabolism in BAT in the fed state. The decrease of TG capacity synthesis
      from 14C-glucose by hSTC-1 compromises the BAT thermogenic capacity. Furthermore,
      the increase in ATP levels would inhibit a futile cycle via UCP-1, which
      dissipates oxidative energy as heat.

PMID- 28435145
TI  - Inhibition of Na+/K+-ATPase by 5,6,7,8-tetrafluoro-3-hydroxy-2-phenylquinolin
      4(1H)-one.
AB  - Na+/K+-ATPase (NKA) is an enzyme of crucial importance for all animal cells. We
      examined the inhibitory effects of halogenated phenylquinolinones on NKA. The
      5,6,7,8-tetrafluoro-3-hydroxy-2-phenylquinolin-4(1H)-one (TFHPQ) was identified
      as an efficient NKA inhibitor with IC50 near 10 MUM. The inhibition by TFHPQ is
      particularly efficient at higher concentrations of K+, where NKA adopts the E2
      conformation. The experimental observations are in a good agreement with the
      outcomes from molecular docking. We identified an energetically favourable TFHPQ
      binding site for the K+-bound NKA, which is located in the proximity of the
      cytoplasmic C-terminus.

PMID- 28435147
TI  - NHS must assess the evidence before closing emergency departments, report warns.

PMID- 28435146
TI  - Prognostic Analysis of Absolute Lymphocyte and Monocyte Counts after Autologous
      Stem Cell Transplantation in Children, Adolescents, and Young Adults with
      Refractory or Relapsed Hodgkin Lymphoma.
AB  - Previous studies in adults have shown that peripheral blood absolute lymphocyte
      and monocyte count ratio (ALC/AMC) after autologous stem cell transplantation
      (ASCT) can predict outcome in patients with relapsed/refractory (R/R) Hodgkin
      lymphoma (HL). We retrospectively reviewed all of our children, adolescent, and
      young adult (CAYA) patients (age <=26) who underwent transplantation for R/R HL
      between 2004 and 2015. Seventy-six patients (median age, 21; range, 10 to 26
      years) who reached day 100 disease free were analyzed; 33% of them had positron
      emission tomography (PET)-positive tumors before ASCT. Patients received high
      dose carmustine, etoposide, cytarabine, and melphalan (n = 40) or
      gemcitabine/busulfan/melphalan (n = 36). Median follow-up after day 100 was 3.9
      years (95% confidence interval [CI], 2.8 to 4.9). A day 100 ALC/AMC ratio >2.1
      correlated with lower risk of relapse (hazard ratio,  .097; 95% CI, .03 to .29; P
      <.0001). Patients with day 100 ALC/AMC ratios >2.1 and <=2.1 had 4-year relapse
      free survival rates of 93% and 33%, respectively (P = .0001) and 4-year overall
      survival rates of 96% and 76%, respectively (P = .0001). In addition, an ALC/AMC
      ratio increase >1.8 from day 15 to day 100 correlated with lower risk of relapse
      (hazard ratio, .24; 95% CI, .08 to 0.73; P = .01). Likewise, an ALC/AMC ratio
      change >.26 from day 30 to day 100 also correlated with a lower likelihood of
      relapse (hazard ratio, .20; 95% CI,  .081 to .51; P = .0007). Multivariate
      analysis showed that a positive PET scan at ASCT, day 100 ALC/AMC ratio <= 2.1,
      and an ALC/AMC ratio change either <=1.8 from day 15 to day 100 or <=.26 from day
      30 to day 100 were independent adverse predictors. In conclusion, our analysis
      confirms in CAYA patients prior observations in adults indicating a major
      prognostic effect of peripheral lymphocyte and monocyte counts at day 100 and
      earlier post-ASCT time points in R/R HL.

PMID- 28435148
TI  - Plasma mediated protein immobilisation enhances the vascular compatibility of
      polyurethane with tissue matched mechanical properties.
AB  - Polyurethanes are a diverse class of polymers, with independently tunable
      mechanical and biodegradation properties making them a versatile platform
      material for biomedical implants. Previous iterations have failed to adequately
      embody appropriate mechanical and biological properties, particularly for
      vascular medicine where strength, compliance and multifaceted biocompatibility
      are required. We have synthesized a new polyurethane formulation with finely
      tuned mechanical properties, combining high strength and extensibility with a low
      Young's modulus. Additional cross-linking during synthesis enhanced stability and
      limits leaching. Under cyclic testing, hysteresis was minimal following
      completion of the initial cycles, indicating the robustness of the material.
      Building on this platform, we used plasma immersion ion implantation to activate
      the polymer surface and functionalized it with recombinant human tropoelastin.
      With tropoelastin covalently bound to the surface, human coronary endothelial
      cells showed improved attachment and proliferation. In the presence of
      heparinized whole blood, tropoelastin-coated polyurethane showed very low
      thrombogenicity in both static and flow conditions. Using this formulation, we
      synthesized robust, elastic prototype conduits which easily retained multiple
      sutures and were successfully implanted in a pilot rat aortic interposition
      model. We have thus created an elastic, strong biomaterial platform,
      functionalized with an important regulator of vascular biology, with the
      potential for further evaluation as a new synthetic graft material.

PMID- 28435149
TI  - Regional Anesthesia Did Not Delay Diagnosis of Compartment Syndrome: A Case
      Report of Anterior Compartment Syndrome in the Thigh Not Masked by an Adductor
      Canal Catheter.
AB  - BACKGROUND Acute compartment syndrome (ACS) of the thigh after elective primary
      total knee arthroplasty is rare. If not recognized and treated promptly,
      devastating consequences may result. Certain regional anesthesia techniques are
      thought to mask the symptoms of acute compartment syndrome, but there are no
      cases reported of adductor canal catheters masking the symptoms of thigh
      compartment syndrome. We report a case where symptoms and diagnosis of acute
      anterior thigh compartment syndrome were not masked by a functioning adductor
      canal catheter. CASE REPORT A 56-year-old male developed anterior thigh
      compartment syndrome after an elective primary total knee arthroplasty. Surgery
      was performed under spinal anesthesia with periarticular local infiltration
      analgesia. Postoperatively, an adductor canal catheter was placed,
      atraumatically, under ultrasound guidance in the recovery room with a plan to
      begin a continuous infusion of 0.2% ropivacaine 10 hours after the periarticular
      injection. Six hours after surgery, the patient complained of tightness and 10/10
      pain in his right thigh, which was initially managed with parenteral opioids with
      moderate success. Continuous infusion through the adductor canal catheter was
      started and pain improved to 6/10 aching pain. Nonetheless, two hours after
      starting the continuous infusion, the patient reported tightness, swelling, and
      10/10 pressure-like pain that was not relieved by the peripheral catheter
      infusion or PRN boluses of additional opioids. Due to the patient's
      symptomatology compartment pressures were measured. The anterior compartment
      pressure was 47 mm Hg and emergent anterior compartment fasciotomy was performed.
      CONCLUSIONS In this case, a functioning adductor canal catheter did not mask
      symptoms of, or delay diagnosis of, acute compartment syndrome in the thigh.

PMID- 28435151
TI  - Osteoarthritis: Targeting peripheral pain neurons in OA.

PMID- 28435150
TI  - YM155 Down-Regulates Survivin and Induces P53 Up-Regulated Modulator of Apoptosis
      (PUMA)-Dependent in Oral Squamous Cell Carcinoma Cells.
AB  - BACKGROUND YM155, which inhibits the anti-apoptotic protein survivin, is known to
      exert anti-tumor effects in various cancers. However, there were few reports
      describing the inhibitory effect of YM155 on human oral squamous cell carcinoma
      (OSCC) cells that highly express survivin. In this study, we investigated the
      anti-tumor effects of YM155 on OSCC cells and then examined its molecular
      mechanisms. MATERIAL AND METHODS SCC9 cells of OSCC were treated with series of
      concentrations of YM155 (0.01, 0.1, 1, and 10 ng/ml) for 6, 12, and 24 h. The
      effect of YM155 on survival of SCC9 cells was detected by MTT and colony
      formation assay. Cell apoptosis was detected by flow cytometric analysis and the
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling
      (TUNEL) assays. Western blot was used to detect the protein expression of
      survivin, p53, and PUMA. Caspase-3 activity was measured by cleavage of the
      caspase-3 substrate. To test the role of PUMA and caspase-3 on YM155-induced
      apoptosis and growth inhibition, the SCC9 cells was transfected with PUMA siRNA
      or caspase-3 siRNA or control siRNA for 16 h before YM155 (1 and 10 ng/ml)
      treatment for 24 h. In addition, we also investigated the effect of YM155 in an
      in vivo xenograft model. RESULTS Treatment of YM155 efficiently reduced survivin
      expression and increased PUMA expression and caspase-3 activation in the SCC9
      cells. YM155 treatment resulted in 18-86% decrease in cell viability, 10-60%
      decrease in colony numbers, and 8-40% increase in cell apoptosis (p<0.05 and
      p<0.01). However, the induction of cell apoptosis growth inhibition was reversed
      by PUMA siRNA or caspase-3 transfection. In addition, animals treated with YM155
      showed more than 60% tumor growth inhibition compared to the controls (p<0.05).
      CONCLUSIONS YM155 is a potent inhibitor of progression of SCC9 cells, which could
      be due to attenuation of survivin, and activation of the PUMA/caspase-3 cellular
      signaling processes. This study suggests that YM155 may be a potential molecular
      target with therapeutic relevance for the treatment of OSCC.

PMID- 28435152
TI  - Systemic lupus erythematosus: Withdrawing standard of care therapies in SLE
      trials?

PMID- 28435153
TI  - Human rhinovirus-induced inflammatory responses are inhibited by
      phosphatidylserine containing liposomes.

PMID- 28435154
TI  - Broadly neutralizing antibodies suppress post-transcytosis HIV-1 infectivity.

PMID- 28435155
TI  - Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the
      pathogenesis of muco-obstructive lung disease.

PMID- 28435156
TI  - Polycystic kidney disease: PMM2 mutation causes PKD and hyperinsulinism.

PMID- 28435158
TI  - A balancing act between IFITM3 and IRF3.

PMID- 28435159
TI  - IFITM3 inhibits virus-triggered induction of type I interferon by mediating
      autophagosome-dependent degradation of IRF3.
AB  - Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that
      can be induced by viral infection and interferons (IFNs). It inhibits the entry
      and replication of many viruses, which are independent of receptor usage but
      dependent on processes that occur in endosomes. In this study, we demonstrate
      that IFITM3 plays important roles in regulating the RNA-virus-triggered
      production of IFN-beta in a negative-feedback manner. Overexpression of IFITM3
      inhibited Sendai virus-triggered induction of IFN-beta, whereas knockdown of
      IFITM3 had the opposite effect. We also showed that IFITM3 was constitutively
      associated with IRF3 and regulated the homeostasis of IRF3 by mediating the
      autophagic degradation of IRF3. These findings suggest a novel inhibitory
      function of IFITM3 on the RNA-virus-triggered production of type I IFNs and
      cellular antiviral responses.

PMID- 28435160
TI  - Anti-CYP4Z1 autoantibodies detected in breast cancer patients.

PMID- 28435161
TI  - Biofilms: Communities in sync.

PMID- 28435162
TI  - Self-regulation and household routines at age three and obesity at age eleven:
      longitudinal analysis of the UK Millennium Cohort Study.
AB  - OBJECTIVE: To examine, in a population-based cohort of 3-year-old children, the
      association between self-regulation and exposure to the household routines of
      regular bedtime, regular mealtime and limits on watching television/video, and to
      determine whether self-regulation and these routines predict the risk of obesity
      at age 11. METHODS: Analyses included 10 955 children in the nationally
      representative UK Millennium Cohort Study. When children were age 3, parents
      reported whether children had a regular bedtime and mealtime, and the amount of
      television/video watched. Emotional and cognitive self-regulation at age 3 were
      assessed by parent-report with the Child Social Behaviour Questionnaire.
      Children's height and weight were measured at age 11 and obesity was defined
      using the International Obesity Task Force (IOTF) criteria. RESULTS: At age 3,
      41% of children always had a regular bedtime, 47% always had a regular mealtime
      and 23% were limited to ?1 h television/video daily. At age 11, 6.2% of children
      were obese. All three household routines were significantly associated with
      better emotional self-regulation, but not better cognitive self-regulation. In a
      multi-variable logistic regression model, including emotional and cognitive self
      regulation, all routines and controlling for sociodemographic covariates, a 1
      unit difference in emotional self-regulation at age 3 was associated with an OR
      (95% CI) for obesity of 1.38 (1.11, 1.71) at age 11, and inconsistent bedtimes
      with an OR (95% CI) for obesity of 1.87 (1.39, 2.51) at age 11. There was no
      evidence that emotional self-regulation mediated the relationship between regular
      bedtimes and later obesity. Cognitive self-regulation was not associated with
      later obesity. CONCLUSIONS: Three-year-old children who had regular bedtimes,
      mealtimes and limits on their television/video time had better emotional self
      regulation. Lack of a regular bedtime and poorer emotional self-regulation at age
      3 were independent predictors of obesity at age 11.

PMID- 28435164
TI  - Navigation: Sounds like non-spatial navigation.

PMID- 28435163
TI  - Progranulin, lysosomal regulation and neurodegenerative disease.
AB  - The discovery that heterozygous and homozygous mutations in the gene encoding
      progranulin are causally linked to frontotemporal dementia and lysosomal storage
      disease, respectively, reveals previously unrecognized roles of the progranulin
      protein in regulating lysosome biogenesis and function. Given the importance of
      lysosomes in cellular homeostasis, it is not surprising that progranulin
      deficiency has pleiotropic effects on neural circuit development and maintenance,
      stress response, innate immunity and ageing. This Progress article reviews recent
      advances in progranulin biology emphasizing its roles in lysosomal function and
      brain innate immunity, and outlines future avenues of investigation that may lead
      to new therapeutic approaches for neurodegeneration.

PMID- 28435165
TI  - Teaching Pharmacology Graduate Students how to Write an NIH Grant Application.
AB  - Objective. To fill the gap in grant writing training in pharmacology graduate
      education using an active-learning strategy. Design. Graduate students wrote
      subsections of a grant according to NIH guidelines. Students revised their
      applications based on multiple rounds of critiques from professors and peers
      throughout a semester-long scientific writing course. Assessment. Prerevision and
      postrevision grant drafts were graded. Students were provided with questionnaires
      assessing their perception of the process. To determine the impact of feedback on
      the proposals, the quality of the pre/postrevision drafts was assessed by
      professors who were blinded and unaffiliated with the course. Conclusion. Student
      grades improved significantly upon resubmission. Perceptions of the proposals by
      blinded faculty members favored revised submissions based on multiple criteria.
      Survey feedback indicated an increase in student confidence in grant writing
      ability. The results of 3 independent measures demonstrate that intensive
      feedback on scientific writing improved the quality of student proposals.

PMID- 28435166
TI  - Fast sampling with Gaussian scale-mixture priors in high-dimensional regression.
AB  - We propose an efficient way to sample from a class of structured multivariate
      Gaussian distributions. The proposed algorithm only requires matrix
      multiplications and linear system solutions. Its computational complexity grows
      linearly with the dimension, unlike existing algorithms that rely on Cholesky
      factorizations with cubic complexity. The algorithm is broadly applicable in
      settings where Gaussian scale mixture priors are used on high-dimensional
      parameters. Its effectiveness is illustrated through a high-dimensional
      regression problem with a horseshoe prior on the regression coefficients. Other
      potential applications are outlined.

PMID- 28435157
TI  - The systemic nature of CKD.
AB  - The accurate definition and staging of chronic kidney disease (CKD) is one of the
      major achievements of modern nephrology. Intensive research is now being
      undertaken to unravel the risk factors and pathophysiologic underpinnings of this
      disease. In particular, the relationships between the kidney and other organs
      have been comprehensively investigated in experimental and clinical studies in
      the last two decades. Owing to technological and analytical limitations, these
      links have been studied with a reductionist approach focusing on two organs at a
      time, such as the heart and the kidney or the bone and the kidney. Here, we
      discuss studies that highlight the complex and systemic nature of CKD. Energy
      balance, innate immunity and neuroendocrine signalling are highly integrated
      biological phenomena. The diseased kidney disrupts such integration and generates
      a high-risk phenotype with a clinical profile encompassing inflammation, protein
      energy wasting, altered function of the autonomic and central nervous systems and
      cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD
      using omics techniques will hopefully enable in-depth study of the
      pathophysiology of this systemic disease, and has the potential to unravel
      critical pathways that can be targeted for CKD prevention and therapy.

PMID- 28435167
TI  - Circulating Tumor Cells in Early-Stage Breast Cancer.
AB  - Disseminated tumor cells (DTC) are routinely detected in bone marrow (BM) in 30
      40 % of primary breast cancer patients. Positive BM status at the time of
      diagnosis as well as DTC persistence after therapy are strong independent
      prognostic factors. Since repeated BM aspirations are not well tolerated,
      detection of single tumor cells in peripheral blood (circulating tumor cells;
      CTC) have become of interest in recent years. CTC are found in 10-80 % breast
      cancer patients. Variability can be explained by stage of the disease and
      detection method. Emerging data have shown CTC to be of prognostic relevance for
      both, patients with primary and metastatic disease. The assessment of CTC in
      blood may become an important biomarker for prognostication and therapy
      monitoring. Determination of their molecular characteristics will enable specific
      targeting of minimal residual as well as metastatic disease. This review
      summarizes recent research and future perspectives.

PMID- 28435168
TI  - How are Interactions Taken into Account in Studies on Conventional and
      Complementary Therapies for Breast Cancer Patients with Menopausal Complaints?
AB  - Introduction: Postmenopausal symptoms in breast cancer patients undergoing
      antihormone treatment lead to high drop-out rates from the therapy. From the
      therapeutic point of view, methods of both conventional and complementary
      medicine are concerned. Interactions are being discussed in cases of natural
      substances. However, they are also relevant for conventional medical substances.
      The aim of this analysis is to answer the question as to what extent potential
      interactions are taken into account in clinical studies and reviews on supportive
      therapies. Materials and Methods: Clinical studies and reviews were identified by
      means of a systematic search and analysed with regard to the consideration of
      potential interactions. Results: Altogether 46 clinical studies and one Cochrane
      review were found. Among the 35 studies on conventional drug therapies, 5 (14 %)
      took possible interactions into account. Among the 17 studies on complementary
      medicine, there were 2 (11.7 %) such publications. The Cochrane review did not
      mention interactions. Discussion: For future studies in which interactions cannot
      be excluded, a strategy to control for their clinically relevant consequences
      should be developed. The present authors suggest that the use of survival and
      recurrence data as secondary endpoints, also for studies on purely supportive
      therapies, is a reasonable approach. The resulting considerations for study
      routines are listed thematically.

PMID- 28435169
TI  - The State of Reproductive Medicine in Germany.
AB  - In the 1960s and 70s, Germany played a leading role in the field of
      gynaecological endocrinology, which was reflected by the scientific activity of
      German universities during this period. More recently, however, a dramatic change
      occurred, resulting in a decreasing number of publications in this field. This
      has undoubtedly contributed to the marginal scientific position of Germany in
      gynaecological endocrinology today. This change is reflected by the decreasing
      number of university centres carrying out active scientific research in the
      fields of gynaecological endocrinology, reproductive medicine and andrology.
      Universities now lack mid- and upper-level faculty staff, as interesting and
      senior positions in the field of reproductive medicine, andrology and
      reproductive medicine no longer exist. Moreover, in 1991 the German embryo
      protection law came into force, which severely curtailed scientific research and
      blocked scientific efforts in this area. German scientists and, of course,
      childless couples were cut off from scientific advances, e.g. the possibility of
      single embryo transfer. Germany's scientific position in the fields of
      gynaecological endocrinology, reproductive medicine and andrology needs to be
      strengthened. The creation of appropriate structures in German universities is
      therefore necessary. These would include important cooperations with private
      medical practices, which currently account for about 75 % of patient care. The
      lines of communication between the groups representing reproductive medicine in
      Germany need to be greatly improved. Moreover, we suggest that an important step
      would be the development of a general human embryology and fertilisation act
      which would allow German couples to benefit from the global advances in the field
      of reproductive technology. Germany must stop its policy of scientific
      obstruction and permit scientific progress in this field in German universities.

PMID- 28435170
TI  - Cervical Strip Biopsy for High-Grade Cervical Intraepithelial Lesions: a Valid
      Alternative to Conventional Punch Technique.
AB  - Introduction: To evaluate, if targeted strip biopsies decrease trauma/pain
      perception while maintaining diagnostic accuracy in patients with the diagnosis
      of high-grade squamous intraepithelial lesions of the uterine cervix. Patients
      and Methods: Between July 1st and December 31st 2014 we performed colposcopically
      directed strip biopsies in 102 patients with colposcopic suspicion of high-grade
      squamous intraepithelial lesions of the uterine cervix. We used a 3 mm curette
      for harvesting tissue samples under VITOM(r) videocolposcopy. So far, 60 patients
      underwent additional loop excision. Histologic examination of strip biopsies and
      loop specimens included routine hematoxylin and eosin staining as well as
      immunohistochemical staining for p16, Ki 67 and stathmin-1. Results: 55 patients
      (53 %), were histologically diagnosed with cervical intraepithelial neoplasia
      grade 3 on strip biopsies. Adenocarcinoma in situ was diagnosed in 2 patients (2
      %), cervical intraepithelial neoplasia grade 2 in 35 patients (34 %), and
      cervical intraepithelial neoplasia grade 1 in 10 patients (10 %). The agreement
      between histologic results of strip biopsy and loop specimen was highly
      significant: In all 60 strip biopsies diagnosed with high-grade squamous
      intraepithelial lesions this diagnosis was confirmed histologically during follow
      up loop specimen excision (high-grade squamous intraepithelial lesions in 58
      patients, invasive disease in 2 patients). The pain level experienced during
      strip biopsy was rated on average 0.25 on a scale from 0 to 10. No clinically
      significant bleeding was reported. Conclusion: Targeted strip biopsies with a 3
      mm curette are a reliable procedure to diagnose high-grade squamous
      intraepithelial lesions of the uterine cervix and yield high patient satisfaction
      (Video 1).

PMID- 28435171
TI  - Experts' Opinion on the Prenatal Therapy of Congenital Adrenal Hyperplasia (CAH)
      Due to 21-Hydroxylase Deficiency - Guideline of DGKED in cooperation with DGGG
      (S1-Level, AWMF Registry No. 174/013, July 2015).
AB  - Purpose: This guideline of the German Society of Pediatric Endocrinology and
      Diabetology (DGKED) is designed to be experts' opinion on the current concept of
      prenatal therapy for congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency (CAH). Several scientific medical societies have also participated in
      the guideline. It aims to offer guidance to physicians when they counsel affected
      families about prenatal therapy. Methods: The experts commissioned by the medical
      societies developed a consensus in an informal process. The consensus was
      subsequently confirmed by the steering committees of the respective medical
      societies. Recommendations: Prenatal CAH therapy is an experimental therapy. We
      recommend designing and using standardized protocols for the prenatal diagnosis,
      therapy and long-term follow-up of women and children treated prenatally with
      dexamethasone. If long-term follow-up is not possible, then prenatal therapy
      should not be performed.

PMID- 28435173
TI  - How attention influences perceptual decision making: Single-trial EEG correlates
      of drift-diffusion model parameters.
AB  - Perceptual decision making can be accounted for by drift-diffusion models, a
      class of decision-making models that assume a stochastic accumulation of evidence
      on each trial. Fitting response time and accuracy to a drift-diffusion model
      produces evidence accumulation rate and non-decision time parameter estimates
      that reflect cognitive processes. Our goal is to elucidate the effect of
      attention on visual decision making. In this study, we show that measures of
      attention obtained from simultaneous EEG recordings can explain per-trial
      evidence accumulation rates and perceptual preprocessing times during a visual
      decision making task. Models assuming linear relationships between diffusion
      model parameters and EEG measures as external inputs were fit in a single step in
      a hierarchical Bayesian framework. The EEG measures were features of the evoked
      potential (EP) to the onset of a masking noise and the onset of a task-relevant
      signal stimulus. Single-trial evoked EEG responses, P200s to the onsets of visual
      noise and N200s to the onsets of visual signal, explain single-trial evidence
      accumulation and preprocessing times. Within-trial evidence accumulation variance
      was not found to be influenced by attention to the signal or noise. Single-trial
      measures of attention lead to better out-of-sample predictions of accuracy and
      correct reaction time distributions for individual subjects.

PMID- 28435174
TI  - Therapist Training on Cognitive Behavior Therapy for Anxiety Disorders Using
      Internet-Based Technologies.
AB  - This study investigated a technology-enhanced training protocol to facilitate
      dissemination of therapist training on cognitive behavior therapy (CBT) for
      anxiety disorders. Seventy community clinicians received an online tutorial
      followed by live remote observation of clinical skills via videoconference.
      Impact of training on patient outcomes was also assessed. Training resulted in a
      significant increase in both trainee knowledge of CBT concepts and techniques and
      therapist competence in applying these skills. Patients treated by trainees
      following training had significant reductions in anxiety and depression. Ratings
      of user satisfaction were high. Results provide support for the use of these
      technologies for therapist training in CBT.

PMID- 28435172
TI  - Diagnosis and Treatment of Hypertensive Pregnancy Disorders. Guideline of DGGG
      (S1-Level, AWMF Registry No. 015/018, December 2013).
AB  - Purpose: Official guideline published and coordinated by the German Society of
      Gynecology and Obstetrics (DGGG). Hypertensive pregnancy disorders contribute
      significantly to perinatal as well as maternal morbidity and mortality worldwide.
      Also in Germany these diseases are a major course for hospitalization during
      pregnancy, iatrogenic preterm birth and long-term cardiovascular morbidity.
      Methods: This S1-guideline is the work of an interdisciplinary group of experts
      from a range of different professions who were commissioned by DGGG to carry out
      a systematic literature search of positioning injuries. Members of the
      participating scientific societies develop a consensus in an informal procedure.
      Afterwards the directorate of the scientific society approves the consensus.
      Recommendations: This guideline summarizes the state-of-art for classification,
      risk stratification, diagnostic, treatment of hypertensive pregnancy disorders.

PMID- 28435176
TI  - Climate shocks and rural-urban migration in Mexico: Exploring nonlinearities and
      thresholds.
AB  - Adverse climatic conditions may differentially drive human migration patterns
      between rural and urban areas, with implications for changes in population
      composition and density, access to infrastructure and resources, and the delivery
      of essential goods and services. However, there is little empirical evidence to
      support this notion. In this study, we investigate the relationship between
      climate shocks and migration between rural and urban areas within Mexico. We
      combine individual records from the 2000 and 2010 Mexican censuses (n=683,518)
      with high-resolution climate data from Terra Populus that are linked to census
      data at the municipality level (n=2,321). We measure climate shocks as monthly
      deviation from a 30-year (1961-1990) long-term climate normal period, and uncover
      important nonlinearities using quadratic and cubic specifications. Satellite
      based measures of urban extents allow us to classify migrant-sending and migrant
      receiving municipalities as rural or urban to examine four internal migration
      patterns: rural-urban, rural-rural, urban-urban, and urban-rural. Among our key
      findings, results from multilevel models reveal that each additional drought
      month increases the odds of rural-urban migration by 3.6%. In contrast, the
      relationship between heat months and rural-urban migration is nonlinear. After a
      threshold of ~34 heat months is surpassed, the relationship between heat months
      and rural-urban migration becomes positive and progressively increases in
      strength. Policy and programmatic interventions may therefore reduce climate
      induced rural-urban migration in Mexico through rural climate change adaptation
      initiatives, while also assisting rural migrants in finding employment and
      housing in urban areas to offset population impacts.

PMID- 28435175
TI  - Hierarchical Feature Selection Incorporating Known and Novel Biological
      Information: Identifying Genomic Features Related to Prostate Cancer Recurrence.
AB  - Our work is motivated by a prostate cancer study aimed at identifying mRNA and
      miRNA biomarkers that are predictive of cancer recurrence after prostatectomy. It
      has been shown in the literature that incorporating known biological information
      on pathway memberships and interactions among biomarkers improves feature
      selection of high-dimensional biomarkers in relation to disease risk. Biological
      information is often represented by graphs or networks, in which biomarkers are
      represented by nodes and interactions among them are represented by edges;
      however, biological information is often not fully known. For example, the role
      of microRNAs (miRNAs) in regulating gene expression is not fully understood and
      the miRNA regulatory network is not fully established, in which case new
      strategies are needed for feature selection. To this end, we treat unknown
      biological information as missing data (i.e., missing edges in graphs), different
      from commonly encountered missing data problems where variable values are
      missing. We propose a new concept of imputing unknown biological information
      based on observed data and define the imputed information as the novel biological
      information. In addition, we propose a hierarchical group penalty to encourage
      sparsity and feature selection at both the pathway level and the within-pathway
      level, which, combined with the imputation step, allows for incorporation of
      known and novel biological information. While it is applicable to general
      regression settings, we develop and investigate the proposed approach in the
      context of semiparametric accelerated failure time models motivated by our data
      example. Data application and simulation studies show that incorporation of novel
      biological information improves performance in risk prediction and feature
      selection and the proposed penalty outperforms the extensions of several existing
      penalties.

PMID- 28435177
TI  - Race and child maltreatment reporting: Are Blacks overrepresented?
AB  - This paper uses Census and child welfare report data from Missouri (1999, 2000 &
      2001) to determine if Whites and Blacks are reported for child maltreatment at
      similar or different rates while controlling for poverty and racial homogeneity.
      We do not find evidence for high levels of racial disproportionality once poverty
      is controlled. Poverty is generally associated with higher rates of reporting for
      both races. We found some evidence of differential sensitivity, with the
      relationship between poverty and report rate being somewhat stronger for Whites
      than for Blacks.

PMID- 28435179
TI  - Real-time measurement of size-resolved elemental composition ratio for flame
      synthesized composite nanoparticle aggregates using a tandem SMPS-ICP-OES.
AB  - Composite nanoparticles find application in catalysis, drug delivery, and energy
      storage and require increasingly fine control of their physical properties and
      composition. While composite nanoparticles have been widely synthesized and
      characterized, little work has systematically correlated the initial
      concentration of precursors and the final composition of flame synthesized
      composite nanoparticles. This relationship is explored in a diffusion flame
      aerosol reactor by coupling a scanning mobility particle sizer (SMPS) with an
      inductively coupled plasma optical emission spectrometer (ICP-OES). A framework
      for studying the relationship between the initial precursor concentrations of
      different elements and the final nanoparticle composition is explored. The size
      resolved elemental composition was measured by directly injecting size-selected
      fractions of aggregated magnetite and silicon dioxide composite nanoparticles
      into the ICP-OES plasma. This work showed a correlation between precursor molar
      ratio and the measured elemental ratio in the mobility size range of 50 to 140
      nm. Building on previous work studying size resolved elemental composition of
      engineered nanoparticles, the analysis is extended to flame synthesized composite
      nanoparticle aggregates in this work.

PMID- 28435178
TI  - Chaotic Experiences and Low-Income Children's Social-Emotional Development.
AB  - Development in early childhood is increasingly likely to take place in multiple
      contexts. Continuity and discontinuity in children's experiences across multiple
      contexts have important implications for their development. This study examines
      the extent to which children experience chaos in their homes and in their
      preschool settings is linked with their social-emotional development over the
      course of the preschool year. Data from a large, representative sample of low
      income preschool children attending Head Start was used to test a series of multi
      level models. Children whose experiences of their homes were highly chaotic,
      regardless of the how chaotic their experiences of their classroom were,
      decreased in their social-emotional skills over the preschool year. Chaotic
      experiences in the home environment thus appear to have more influence on
      children's development than do chaotic preschool experiences.

PMID- 28435180
TI  - Silence is not golden: the hissing calls of tits affect the behaviour of a nest
      predator.
AB  - ABSTRACT: Nest predation is one of the most important mortality factors of birds.
      Field observations showed that tits (Paridae) produce hissing calls and, usually,
      have lower breeding losses than nesting Ficedula flycatchers, which do not make
      such calls. We hypothesise that differences in fledgling success can be directly
      attributed to the vocal reaction of tits. We tested experimentally whether the
      hissing calls can affect the behaviour of a potential predator, analysing the
      response of the Yellow-necked Mouse Apodemus flavicollis to playback of calls of
      three Parid species. The number of visits by mice to two types of cavities (with
      playback and control) was not significantly different, but the average time spent
      by mice in cavities with playback (3.9 s) was significantly shorter than in
      cavities without playback (26.3 s). This suggests that hissing behaviour of tits
      significantly changes the exploration activity of predators, which may ultimately
      increase the breeding success of this group of birds relative to the flycatchers.
      SIGNIFICANCE STATEMENT: Nest predation is one of the most important mortality
      factors of small land birds, but some anti-predatory mechanisms are still poorly
      recognised. Numerous studies demonstrate that incubating tits make hissing
      sounds, when a predator is near, but despite almost a century of research, there
      is little evidence these calls indeed affect behaviour of predators. By using a
      simple laboratory experiment, we demonstrated that the hissing acoustic signals
      used by tits may change the behaviour of yellow-necked mice, which are an
      important predator of cavity-nesting birds in temperate forests. Intruding mice
      withdrew from cavities where hissing sounds were played back. Our results suggest
      that the hissing behaviour of tits can change the exploration activity of
      potential predators and may increase breeding success of this group of birds
      relative to the flycatchers, which stay silent when their nest is threatened.

PMID- 28435181
TI  - Orthogonality of the Mean and Error Distribution in Generalized Linear Models.
AB  - We show that the mean-model parameter is always orthogonal to the error
      distribution in generalized linear models. Thus, the maximum likelihood estimator
      of the mean-model parameter will be asymptotically efficient regardless of
      whether the error distribution is known completely, known up to a finite vector
      of parameters, or left completely unspecified, in which case the likelihood is
      taken to be an appropriate semiparametric likelihood. Moreover, the maximum
      likelihood estimator of the mean-model parameter will be asymptotically
      independent of the maximum likelihood estimator of the error distribution. This
      generalizes some well-known results for the special cases of normal, gamma and
      multinomial regression models, and, perhaps more interestingly, suggests that
      asymptotically efficient estimation and inferences can always be obtained if the
      error distribution is nonparametrically estimated along with the mean. In
      contrast, estimation and inferences using misspecified error distributions or
      variance functions are generally not efficient.

PMID- 28435182
TI  - A Collaboration for Health and Wellness: GRIOT Circle and Caring and Aging with
      Pride.
AB  - Despite growing racial and ethnic diversity among lesbian, gay, bisexual,
      transgender, and queer (LGBTQ) older adults in the United States, LGBTQ older
      adults of color largely are invisible in aging services, research, and public
      policy. GRIOT Circle and Caring and Aging with Pride are pioneering efforts in
      community-based services and research. This article describes innovative and
      effective ways to reach and serve LGBTQ older adults of color, how research can
      be designed collaboratively to address strengths and disparities in social,
      health, and economic well-being, and barriers to accessing aging services in
      these populations.

PMID- 28435183
TI  - A Factor Analytic Model of Drug-Related Behavior in Adolescence and Its Impact on
      Arrests at Multiple Stages of the Life Course.
AB  - OBJECTIVES: Recognizing the inherent variability of drug-related behaviors, this
      study develops an empirically-driven and holistic model of drug-related behavior
      during adolescence using factor analysis to simultaneously model multiple drug
      behaviors. METHODS: The factor analytic model uncovers latent dimensions of drug
      related behaviors, rather than patterns of individuals. These latent dimensions
      are treated as empirical typologies which are then used to predict an
      individual's number of arrests accrued at multiple phases of the life course. The
      data are robust enough to simultaneously capture drug behavior measures typically
      considered in isolation in the literature, and to allow for behavior to change
      and evolve over the period of adolescence. RESULTS: Results show that factor
      analysis is capable of developing highly descriptive patterns of drug offending,
      and that these patterns have great utility in predicting arrests. Results further
      demonstrate that while drug behavior patterns are predictive of arrests at the
      end of adolescence for both males and females, the impacts on arrests are longer
      lasting for females. CONCLUSIONS: The various facets of drug behaviors have been
      a long-time concern of criminological research. However, the ability to model
      multiple behaviors simultaneously is often constrained by data that do not
      measure the constructs fully. Factor analysis is shown to be a useful technique
      for modeling adolescent drug involvement patterns in a way that accounts for the
      multitude and variability of possible behaviors, and in predicting future
      negative life outcomes, such as arrests.

PMID- 28435184
TI  - Mining Electronic Health Records Data: Domestic Violence and Adverse Health
      Effects.
AB  - Intimate partner violence (IPV) often culminates in acute physical injury, sexual
      assault, and mental health issues. It is crucial to understand the healthcare
      habits of victims to develop interventions that can drastically improve a
      victim's quality of life and prevent future abuse. The objective of this study is
      to mine de-identified and aggregated Electronic Health Record data to identify
      women's health issues that are potentially associated with IPV. In this study we
      compared health issues of female domestic abuse victims to female non-domestic
      abuse victims. The Domestic abuse population contained 5870 patients, while the
      Non-Domestic Abuse population contained 14,315,140 patients. Explorys provides
      National Big Data from the entire USA. Statistical analysis identified 2429 terms
      as significantly more prevalent among victims of domestic abuse, compared to the
      general population. These terms were classified into broad categories, including
      acute injury, chronic conditions, substance abuse, mental health, disorders,
      gynecological and pregnancy related problems.

PMID- 28435186
TI  - A Low-Power Thermal-Based Sensor System for Low Air Flow Detection.
AB  - Being able to rapidly detect a low air flow rate with high accuracy is essential
      for various applications in the automotive and biomedical industries. We have
      developed a thermal-based low air flow sensor with a low-power sensor readout for
      biomedical applications. The thermal-based air flow sensor comprises a heater and
      three pairs of temperature sensors that sense temperature differences due to
      laminar air flow. The thermal-based flow sensor was designed and simulated by
      using laminar flow, heat transfer in solids and fluids physics in COMSOL
      MultiPhysics software. The proposed sensor can detect air flow as low as 0.0064
      m/sec. The readout circuit is based on a current- controlled ring oscillator in
      which the output frequency of the ring oscillator is proportional to the
      temperature differences of the sensors. The entire readout circuit was designed
      and simulated by using a 130-nm standard CMOS process. The sensor circuit
      features a small area and low-power consumption of about 22.6 uW with an 800 mV
      power supply. In the simulation, the output frequency of the ring oscillator and
      the change in thermistor resistance showed a high linearity with an R2 value of
      0.9987. The low-power dissipation, high linearity and small dimensions of the
      proposed flow sensor and circuit make the system highly suitable for biomedical
      applications.

PMID- 28435185
TI  - Influence of Rb/Cs Cation-Exchange on Inorganic Sn Halide Perovskites: From
      Chemical Structure to Physical Properties.
AB  - CsSnI3 is a potential lead-free inorganic perovskite for solar energy
      applications due to its nontoxicity and attractive optoelectronic properties.
      Despite these advantages, photovoltaic cells using CsSnI3 have not been
      successful to date, in part due to low stability. We demonstrate how gradual
      substitution of Rb for Cs influences the structural, thermodynamic, and
      electronic properties on the basis of first-principles density functional theory
      calculations. By examining the effect of the Rb:Cs ratio, we reveal a correlation
      between octahedral distortion and band gap, including spin-orbit coupling. We
      further highlight the cation-induced variation of the ionization potential (work
      function) and the importance of surface termination for tin-based halide
      perovskites for engineering high-performance solar cells.

PMID- 28435187
TI  - Effect of food processing on degradation of hexachlorocyclohexane and its isomers
      in milk.
AB  - AIM: To study the effect of different food processing techniques on the
      degradation of organochlorine compounds (alpha, beta, gamma and delta
      hexachlorocyclohexane isomers (HCH)) residues in both natural and fortified
      samples of milk. MATERIALS AND METHODS: Raw milk samples are collected from the
      local areas of Hyderabad, India. Naturally and fortified milk samples (HCH) were
      subjected to various food processing techniques, pasteurization (63oC for 1/2 h),
      sterilization (121oC for 15 min) and boiling for 5 min and analyzed by gas
      chromatography with electron capture detector using quick, easy, cheap,
      effective, rugged and safe method for multiresidue analysis of pesticides in milk
      with slight modification. RESULTS: The final mean residual concentration of
      pesticide in milk after heat processing and percentage of degradation were
      calculated with respective treatments. CONCLUSION: Heat treatments are highly
      effective on reduction of mean residual concentration of HCH in milk. In which
      Sterilization and boiling proved to be more effective in degradation of HCH
      isomers.

PMID- 28435188
TI  - Effect of kisspeptin on in vitro maturation of sheep oocytes.
AB  - AIM: The aim of this study was to investigate the effect of kisspeptin (KP) on in
      vitro maturation (IVM) of sheep oocytes aspirated from the ovaries collected from
      slaughterhouse. MATERIALS AND METHODS: Two different experiments were conducted
      to investigate the effect of KP (5, 10 and 15 ug/ml) alone (experiment 1) or in
      combination with follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      and Estradiol (E2) (experiment 2) on IVM of sheep oocytes. Tissue culture medium
      199 supplemented with Gentamicin was used as control medium. Good quality oocytes
      were randomly allocated into different IVM media and cultured at 38.5 degrees C
      in 5% CO2 under humidified atmosphere for 24 h. The oocytes were evaluated for
      their cumulus cell expansion (CCE) and extrusion of the 1st polar body (PB) at
      the end of maturation. RESULTS: The proportion of oocytes showing CCE and
      extrusion of PB was highest when the oocytes were matured in the medium
      supplemented with 10 ug/ml of KP. In experiment 2, oocytes were matured in 12
      different maturation media (G1-G12: G1: Control, G2: KP alone, G3: FSH, G4:
      FSH+KP, G5: LH, G6: LH+KP, G7: E2, G8: E2+KP, G9: FSH+LH+E2, G10: FSH+LH+E2+KP,
      G11: FSH+LH+E2+fetal bovine serum (FBS), G12: FSH+LH+E2+FBS+KP). The proportion
      of oocytes showing cumulus expansion and PB extrusion was highest (98.33+/-1.05
      and 89.17+/-2.38) when they were matured in FSH+LH+E2+FBS+KP (G12) and was
      significantly higher than other groups. The proportion of CCE and extrusion of PB
      was significantly increased when KP was supplemented to FSH and E2, but no effect
      was observed with LH. The maturation rates were significantly increased when FSH,
      LH, and E2 (G9) containing media were additionally supplemented with KP (G10).
      CONCLUSION: This study demonstrated that the addition of KP (10 ug/ml) to the
      FSH, LH, and E2 supplemented media would enhance the sheep oocyte maturation in
      vitro.

PMID- 28435189
TI  - In vitro evaluation of total mixed ration supplemented with exogenous fibrolytic
      enzymes for crossbred cows.
AB  - AIM: The study was conducted to evaluate the levels of exogenous fibrolytic
      enzymes (EFE) on in vitro digestibilities of dry matter (DM) and organic matter
      (OM), total gas production (TGP), metabolizable energy (ME) content, and
      microbial biomass production (MBP). MATERIALS AND METHODS: The total mixed ration
      (TMR) was prepared using 30% each of sorghum hay and groundnut straw and 40%
      compound concentrate mixture to meet nutritional requirement of cow (500 kg)
      producing 12 kg fat corrected milk. The EFE was incorporated at 0, 40, 60, 80,
      100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, and
      400 mg/kg TMR. The TMR substrates with different levels of EFE were in vitro
      incubated to ascertain their effect on digestibility, gas production, and
      nutritive values. RESULTS: The significantly (p<0.05) higher and optimum in vitro
      digestibilities of DM (63.03%) and OM (63.62%) as well as TGP (72.35 ml/500 mg
      TMR) were observed at supplementation of 240 mg EFE/kg TMR, while ME (7.16 MJ/kg
      DM) and MBP (97.63 mg/500 mg TMR) were also better. CONCLUSION: The incorporation
      of EFE at 240 mg/kg TMR resulted significantly (p<0.05) higher and optimum in
      vitro digestibilities of DM and OM. The TGP, ME, and MBP were also better. The
      levels of EFE 240 mg/kg TMR were found suitable for further in vivo study in
      crossbred cows.

PMID- 28435190
TI  - Prevalence of Salmonella in poultry processing environments in wet markets in
      Penang and Perlis, Malaysia.
AB  - AIM: The aim of this study was to determine the prevalence of various Salmonella
      serotypes in chickens, carcass contact surfaces as well as environmental samples
      collected from wet markets and small scale processing plant. MATERIALS AND
      METHODS: A total of 182 poultry and environmental samples were collected at
      random on separate occasions from wet markets and small scale processing plant,
      during the period of October 2014 to July 2015 in Penang and Perlis, Malaysia.
      The samples were analyzed for the presence of Salmonella using ISO 6579:2002
      conventional culture-based method. Presumptive Salmonella colonies were subjected
      to various biochemical tests (such as triple sugar iron and lysine iron test),
      serologically confirmed using polyvalent O and H antisera and further serotyped
      at Public Health Laboratory, Ministry of Health, Perak, Malaysia. RESULTS:
      Salmonella serotypes were isolated from 161 out of 182 samples (88.46%) with 100%
      prevalence in the whole chicken carcass and chicken cuts - as well as transport
      crate, cage, drum, knife, chopping board, display table, floor, bench wash water,
      wash water, and drain water. Salmonella was isolated from 91.67%, 83.33%, and
      66.67% of defeathering machines, drain swabs, and apron, respectively. 17
      serotypes were isolated in this study with Salmonella Albany (57/161), Salmonella
      Corvallis (42/161), and Salmonella Brancaster (37/161) being the predominant
      serovars. CONCLUSION: The most carcass contact and environmental samples
      collected along the wet market chicken processing line were consistently
      contaminated with Salmonella. This indicates that Salmonella has established
      itself in poultry processing environments by colonizing the surfaces of the
      equipment and survives in these environments by establishing biofilms. Our
      results highlight the need of implementing strict hygiene and sanitation
      standards to reduce the incidence of Salmonella. The prevalence of Salmonella in
      poultry can be reduced effectively by identifying and eliminating the sources and
      contamination sites during slaughter and processing of poultry.

PMID- 28435191
TI  - Occurrence of multidrug resistant Escherichia coli in groundwater of Brij region
      (Uttar Pradesh) and its public health implications.
AB  - AIM: The study evaluates the microbial as well as physicochemical pollution of
      groundwater of Brij region of Uttar Pradesh, a major tourist destination in the
      country along with estimating the drug resistance evident in the isolated
      Escherichia coli. MATERIALS AND METHODS: A total of 60 samples of groundwater
      were collected from six different sites and assessed for physicochemical (pH,
      color, taste, turbidity, total dissolved solids [TDS], total hardness [TH],
      chlorides, fluorides, nitrates, and iron) and microbiological parameters
      (standard plate count [SPC], most probable number test [MPN], E. coli). RESULTS:
      A majority of the samples were found to be out of the range for most of the
      parameters except iron. Particularly, high values of TDS (up to 9000 ppm), TH
      (1500 mg/L), chlorides (3250 mg/L), fluorides (2.5 mg/L), and nitrates (100.2
      mg/L) were observed at most of the sites in the region highlighting the fact that
      groundwater of the area is not potable. Samples were turbid and salty to taste.
      High SPC values, up to 3500 colony-forming unit/ml and coliforms beyond BIS range
      were found in 40% samples suggesting gross microbial contamination. Only 2 sites
      (G3 and G5) had low MPN values. Overall 16 (26.67%) E. coli were isolated with 3
      (18.75%) producing red colonies on conge red agar, hence supposed to be
      pathogenic. No E. coli O157:H7 was isolated. High antimicrobial resistance was
      observed against amoxicillin and erythromycin, whereas E. coli isolates were
      sensitive toward cefotaxime-clavulanic acid and imipenem. 12 isolates (75%) were
      multidrug resistant (MDR) with MDR index >20%, and 2 isolates (12.5%) were found
      to be extended spectrum beta-lactamases positive. CONCLUSION: Groundwater is
      considered to be a safe option for potable water but it is obvious from the
      findings of this study that considerable physicochemical and microbial
      contamination is there in groundwater samples of Brij region. The occurrence of
      MDR E. coli in these waters is a matter of great public health concern.

PMID- 28435192
TI  - Effect of peripartum nutritional management on plasma profile of steroid
      hormones, metabolites, and postpartum fertility in buffaloes.
AB  - AIM: The aim of this study was to evaluate the influence of peripartum protein
      and minerals supplementation on plasma profile of steroid hormones, metabolites,
      and fertility in rural buffaloes. MATERIAL AND METHODS: A total of 85 advanced
      pregnant (~8 months) pluriparous buffaloes selected at farmers' doorstep in three
      tribal villages of Middle Gujarat were randomly divided into two groups, viz.,
      control (n=45) and nutrients treatment (40). The buffaloes of treatment group
      (n=40), in addition to farmers feeding schedule/control, received daily 1.5 kg
      compound concentrate mixture (22% CP) and 50 g of chelated ASMM for 2 months each
      pre- and post-partum. Further, 15 buffaloes, each of control and treatment group,
      were injected parentrally (deep i/m) with 5 ml of micro-minerals (each ml
      containing Se, Zn, Cu and Mn at 5, 40, 15 and 10 mg, respectively), twice 2
      months before and on the day of calving, keeping rest of the animals (control,
      n=30 and treatment, n=25) as controls. Blood sampling was done on days -60, -30, 
      15, 0, 15, 30, 45, and 60 peripartum for estimation of plasma progesterone and
      estradiol by standard RIA techniques and other metabolites using assay kits on
      biochemistry analyzer. The puerperal events and postpartum fertility were
      monitored through history and by fortnightly palpation per rectum till day 45 and
      then again at 120 days postpartum for both the groups and subgroups. RESULTS: The
      mean plasma progesterone concentrations in all groups declined significantly
      (p<0.05) from day 60 to day 15 prepartum, reached to the basal levels (<0.5
      ng/ml) on the day of parturition, and subsequently, reduced nonsignificantly till
      day 15 postpartum and then showed a rising trend from day 30 to 60 postpartum
      with significantly higher values at day 45 and/or 60. The mean plasma estradiol
      values increased with approaching parturition and were at its peak on the day of
      calving (p<0.01). Thereafter, there was a rapid fall in the levels by day 15 and
      it remained low till day 45-60 postpartum. The blood glucose values showed an
      increasing trend with advancing gestation, reaching the highest on the day of
      calving, dropped significantly (p<0.01) within 15 days postpartum, and thereafter
      showed consistent values. The buffaloes supplemented with peripartum nutrients
      maintained significantly (p<0.05) higher blood glucose concentrations than the
      control during the peak lactation. The plasma protein levels varied significantly
      (p<0.05) between days within the group with the lowest values on the day of
      calving, as well as between groups with higher (p<0.05) values on day 30 and 60
      postpartum in treated group. Micro-minerals injected did not reveal significant
      influence on steroid hormones, blood glucose, or plasma protein. The mean plasma
      total cholesterol was significantly lower (p<0.05) in treatment than the control
      group. The mean values in micro-minerals injected subgroup were higher than the
      non-injected control subgroup during postpartum phase. The mean plasma
      triglyceride values in the pregnant buffaloes under both the groups and subgroups
      gradually decreased as parturition approached with significantly lowest values on
      the day of calving. The values increased nonsignificantly by day 15 and then
      remained steady throughout postpartum period without influence of nutrient
      supplementation or micro-minerals injection. The incidence of retained fetal
      membranes (RFMs) was 5.00 and 13.33% in treatment and control groups,
      respectively, with placental expulsion time of 3.27+/-0.37 and 4.44+/-0.53 h
      (p>0.05). The micro-minerals injection appreciably reduced the incidence of RFMs
      and significantly (p<0.05) reduced the placental expulsion time over non-injected
      controls. In treatment group, the period for involution of uterus was
      significantly shorter (29.39+/-0.50 vs. 32.12+/-0.82 days, p<0.05), with early
      onset of first postpartum estrus (67.65+/-1.67 vs. 79.43+/-3.06 days, p<0.01),
      shorter service period (90.89+/-4.41 vs. 105.09+/-4.76 days, p<0.05) and higher
      conception rate (55.00 vs. 40.00%) than in control group. The micro-minerals
      injection apparently and/or significantly improved all these traits in both the
      groups. Thus, the postpartum reproductive performance was significantly improved
      in treated than control groups and subgroups. CONCLUSION: The results showed that
      nutrient supplementation in terms of high protein concentrate, ASMM and injection
      of sustained release micro-minerals (Se, Zn, Cu, and Mn) during transition period
      minutely altered the plasma steroid hormones and blood metabolites though it
      significantly improved the postpartum reproductive performance in buffaloes under
      field conditions.

PMID- 28435194
TI  - Molecular characterization of velogenic viscerotropic Ranikhet (Newcastle)
      disease virus from different outbreaks in desi chickens.
AB  - AIM: Diagnosis of velogenic viscerotropic Ranikhet disease from six different
      flocks of desi chicken in and around Mumbai by gross and histopathological
      examination, isolation of virus and molecular methods. MATERIALS AND METHODS: A
      total of 25 carcasses (varying between 2 and 6 carcasses from each flock) of six
      different flocks of adult desi chicken were subjected to necropsy examination for
      diagnosis of the disease during the span of a year (2014-2015). After thorough
      gross examination, the tissue samples were collected and processed for virus
      isolation and histopathological examination. The 20% tissue homogenate was
      inoculated into 9-day-old specific pathogen free (SPF) embryonated eggs. Mean
      death time (MDT) of embryos after inoculation and intracerebral pathogenicity
      index (ICPI) were used to judge velogenic nature of the virus. Newcastle disease
      virus (NDV) was isolated from six cases and confirmed by reverse transcriptase
      polymerase chain reaction (RT-PCR) targeting the partial fusion protein gene of
      the viral genome. RESULTS: A total of 25 carcasses (varying between 2 and 6
      carcasses from each flock) of six different flocks of desi chicken were presented
      for postmortem examination to Department of Veterinary Pathology, Bombay
      Veterinary College, Parel, Mumbai during 2014-2015. The gross and
      histopathological examination revealed lesions suggestive of viscerotropic
      velogenic form of the Newcastle disease (ND). The 20% tissue homogenate was
      inoculated into 9-day-old embryonated eggs from SPF chicken. NDV was isolated
      from six cases and confirmed by RT-PCR targeting the partial fusion protein gene.
      MDT of all the isolates was <60 h which indicated velogenic nature of the virus.
      ICPI of the isolates ranged between the 1.63 and 1.78. In four out of six
      outbreaks concurrent moderate to heavy infection of Ascardii galli in one flock
      and Railetina spp. in three flocks was also noted. In this study, viscerotropic
      velogenic form of ND was confirmed in all six outbreaks by gross and microscopic
      examination, virus isolation and RT-PCR. CONCLUSIONS: In this study,
      viscerotropic velogenic form of ND was confirmed in all six outbreaks by gross
      and microscopic examination, virus isolation and RT-PCR. Nowadays, vaccine
      strains Lasota, B1 and F strains are used widely in India to control the
      infection of NDV. However, virulent NDV strains are still isolated frequently in
      the birds under backyard and also in commercial venture which demonstrates that
      NDV remains an on-going threat to commercial as well as backyard poultry flocks.

PMID- 28435193
TI  - Can methicillin-resistant Staphylococcus aureus prevalence from dairy cows in
      India act as potential risk for community-associated infections?: A review.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is classified as hospital
      associated (HA), community associated (CA), livestock associated (LA) and is a
      global concern. Developing countries, like India, are densely populated country
      challenging for public hygiene practices. HA-MRSA is comfortably recorded in
      India, and CA-MRSA is also reported as increasing one. CA-MRSA is serious disease
      which affects the community as endemic. MRSA is one among major mastitis-causing
      organisms in India as LA-MRSA. There were reports for transmission of MRSA as
      community between milk handlers and cow in global perspective. In India reports
      of MRSA in short among milk handlers and also transmission between animal and
      human. Hence, proper monitoring of MRSA transmission in India should be
      elucidated in account among milk handlers and dairy cows to avoid emerging CA
      MRSA as outbreak.

PMID- 28435195
TI  - Intestinal microbial ecology and hematological parameters of broiler fed cassava
      waste pulp fermented with Acremonium charticola.
AB  - AIM: The aim of this study was to evaluate the effect of feeding Acremonium
      charticola-fermented cassava pulp (AC-FCP) on the intestinal microbial ecology
      and hematological indices of broiler chickens. MATERIALS AND METHODS: A total of
      240 male Lohman day-old-chicks were randomly allotted to one of the four
      experimental diets including control diet, control diet + antimicrobials
      (neomycin; 300 mg/kg diet), diet containing AC-FCP (16 g/100 g diet) or diet
      containing AC-FCP + antimicrobials. At day 28, the birds from each pen were blood
      sampled, sacrificed and immediately the internal organs were removed and weighed.
      Digesta were obtained from the ileum and cecum. RESULTS: Birds fed AC-FCP had
      lower (p<0.05) coliform bacteria count in the ileal digesta than birds fed
      control diet or control diet + antimicrobials. Butiric acid was higher (p<0.05)
      in the cecal content of birds fed AC-FCP than in other birds. Propionic acid was
      also higher in AC-FCP fed birds than in other birds although statistically not
      significant. The percentages of lymphocytes and heterophils were higher (p<0.05)
      and tended (p=0.07) to be lower, respectively, in broilers fed control diet than
      in other birds. The birds provided control diet had lower (p<0.05) heterophils to
      lymphocytes ratio compared to those receiving AC-FCP or AC-FCP + antimicrobials.
      Serum total protein and globulin were higher (p<0.01) in birds fed control diet
      or control diet + antimicrobials compared to AC-FCP or AC-FCP + antimicrobials
      fed birds. Serum albumin was lower (p<0.01) in AC-FCP birds than that in other
      birds. There was a tendency (p=0.09) that birds fed AC-FCP diet had lower total
      serum cholesterol than other birds. CONCLUSION: Feeding AC-FCP has potential to
      improve the intestinal health and protect the birds from acute infections.

PMID- 28435196
TI  - Hemato-biochemical alterations and urinalysis in dogs suffering from benign
      prostatic hyperplasia.
AB  - AIM: The study was designed to evaluate the hemato-biochemical alterations,
      urinalysis along with histomorphological and histological changes of prostate
      glands in dogs affected with benign prostatic hyperplasia (BPH) in and around
      Bhubaneswar, Odisha, India. MATERIALS AND METHODS: In toto, 445 dogs presented to
      the Teaching Veterinary Clinical Complex of the College of Veterinary Sciences
      and Animal Husbandry, one Government Veterinary Hospital and two pet clinics in
      and around Bhubaneswar screened for the presence of BPH. Most of the 57 dogs were
      6 years and above as reported by the owners. Only 57 dogs found positive for BPH
      basing on the presence of typical clinical signs subjected for a detailed hemato
      biochemical study. Most of the 57 dogs were 6 years and above as reported by the
      owners. Routine and microscopic urinalyses were done as per the routine
      procedure. Histomorphological evaluations of prostate glands were done through
      manual rectal palpation. Histological examinations of prostate tissue sections of
      two dead dogs were conducted with routine hematoxylin and eosin stain. RESULTS:
      The study revealed about 12.8% (57/445) of dogs was suffering from BPH. Typical
      clinical signs - such as passing small thin tape-shaped feces, holding tail away
      from backward, tenesmus, and straining during urination and defecation - were
      seen in most of the cases. Urine samples of affected dogs were positive for
      glucose, occult blood, and protein. A significant decrease in lymphocytes and
      increase in eosinophil counts in dogs with BPH was recorded. Serum biochemical
      analysis showed a nonsignificant increase in creatinine and blood urea nitrogen
      with a significant decrease in total protein, albumin, globulin, A:G ratio.
      Histology of prostate glands collected during postmortem was characterized by
      fibrosis of prostate gland, and hyperplasia of the acinar epithelium.
      CONCLUSIONS: High rate of the prevalence of BPH in dogs poses an alarming
      condition which if diagnosed at an early stage can certainly prolong the
      longevity of the dogs.

PMID- 28435197
TI  - Development of nested polymerase chain reaction-based diagnosis of duck enteritis
      virus and detection of DNA polymerase gene from non-descriptive duck breeds of
      West Bengal, India.
AB  - AIM: The study was undertaken to detect the clinical signs, postmortem lesions of
      embryonated duck plague (DP) infected eggs, and histopathological changes of
      chorioallantoic membrane (CAM) in non-descriptive ducks of West Bengal with
      special reference to standardize nested polymerase chain reaction (PCR).
      MATERIALS AND METHODS: After postmortem of suspected carcasses, samples were
      collected for virus isolation and identification through specific pathogen free
      (Khaki Campbell) embryonated duck eggs. PCR was also done as confirmatory test
      after doing postmortem of duck embryos. DP specific nested PCR was standardized
      for better confirmation of the disease. Sensitivity of nested primers was also
      tested for DP virus. RESULTS: Gross, postmortem and histopathological changes
      were prominent in dead embryos. First set of primer was able to detect 602 bp
      fragments of DNA polymerase gene of duck enteritis virus from infected CAM.
      Subsequently, a DP specific nested PCR which was very much sensitive for very
      small amount of viral genome was successfully standardized. After NCBI blast
      nucleotide sequence of nested PCR product (Accession No. HG425076) showed
      homology with the sequences data available in GenBank. CONCLUSION: The study
      concludes that PCR assay is very much helpful to diagnose DP disease and
      developed nested PCR is a double confirmatory diagnostic tool for DP.

PMID- 28435198
TI  - Association between udder morphology and in vitro activity of milk leukocytes in
      high yielding crossbred cows.
AB  - AIM: The present investigation was conducted to study the association between
      udder morphology and in vitro activity of milk leukocytes in high yielding
      crossbred cows. MATERIALS AND METHODS: A total of 48 healthy high yielding
      crossbred cows were selected for the study. The udder configuration and
      teat/udder morphology were recorded before milking. Milk samples (100 ml/cow)
      were collected aseptically. Milk somatic cell counts (SCC) and milk differential
      leukocyte counts were performed microscopically. Milk leukocytes (viz.,
      neutrophils, lymphocytes, and macrophages) were isolated from milk samples by
      density gradient centrifugation. Phagocytic index (PI) of milk neutrophils and
      macrophages were evaluated by colorimetric nitro blue tetrazolium assay.
      Lymphocytes proliferation response was estimated by MTT assay and expressed as
      stimulation index. RESULTS: There was a significant (p<0.01) positive correlation
      between milk SCC with mid teat diameter, teat base diameter and significant
      (p<0.05) negative correlation between milk SCC and the height of the teat from
      the ground. Milk SCC was found to be significantly (p<0.01) lower in bowl-shaped
      udder and higher (p<0.01) in pendulous type. Milk macrophage percentage was
      positively (p<0.01) correlated with udder circumference. PI of milk neutrophil
      was negatively (p<0.01) correlation between teat base diameter, and PI of milk
      macrophages was found to be positively (p<0.01) correlated with teat apex
      diameter. Both PI of milk neutrophils and macrophages was found to be
      significantly (p<0.01) lower in the animals having flat and round teat and
      pendulous type of udder. In vitro PI of milk neutrophils was found to be
      significantly (p<0.01) lower in flat teat. In vitro PI of milk macrophages was
      found to be significantly (p<0.01) lower in the round and flat teats compared to
      pointed and cylindrical teats. CONCLUSION: Udder risk factors such as teat shape
      and size, teat to floor distance, udder shape, and size may decrease the in vitro
      activity of milk leukocytes hence facilitates the incidence intramammary
      infections.

PMID- 28435199
TI  - Genetic characterization of the non-structural protein-3 gene of bluetongue virus
      serotype-2 isolate from India.
AB  - AIM: Sequence analysis and phylogenetic studies based on non-structural protein-3
      (NS3) gene are important in understanding the evolution and epidemiology of
      bluetongue virus (BTV). This study was aimed at characterizing the NS3 gene
      sequence of Indian BTV serotype-2 (BTV2) to elucidate its genetic relationship to
      global BTV isolates. MATERIALS AND METHODS: The NS3 gene of BTV2 was amplified
      from infected BHK-21 cell cultures, cloned and subjected to sequence analysis.
      The generated NS3 gene sequence was compared with the corresponding sequences of
      different BTV serotypes across the world, and a phylogenetic relationship was
      established. RESULTS: The NS3 gene of BTV2 showed moderate levels of variability
      in comparison to different BTV serotypes, with nucleotide sequence identities
      ranging from 81% to 98%. The region showed high sequence homology of 93-99% at
      amino acid level with various BTV serotypes. The PPXY/PTAP late domain motifs,
      glycosylation sites, hydrophobic domains, and the amino acid residues critical
      for virus-host interactions were conserved in NS3 protein. Phylogenetic analysis
      revealed that BTV isolates segregate into four topotypes and that the Indian BTV2
      in subclade IA is closely related to Asian and Australian origin strains.
      CONCLUSION: Analysis of the NS3 gene indicated that Indian BTV2 isolate is
      closely related to strains from Asia and Australia, suggesting a common origin of
      infection. Although the pattern of evolution of BTV2 isolate is different from
      other global isolates, the deduced amino acid sequence of NS3 protein
      demonstrated high molecular stability.

PMID- 28435200
TI  - Mycotoxin binders potential on histological of ovary mice exposed by zearalenone.
AB  - AIM: This study was conducted to examine the potential of mycotoxin binder in
      ceasing zearalenone (ZEN) effect on mice reproduction. ZEN mycotoxin can induce
      reactive oxygen species that may cause damage and cell death. ZEN is estrogenic
      so that it may affect the reproductive organs failure. MATERIALS AND METHODS:
      Mycotoxin binder administration to female mice exposed to ZEN was aimed to count
      the number of primary follicles, secondary follicles, tertiary follicles, de
      Graaf's follicles, and the corpus luteum (CL). Negative control group (C) was not
      exposed to ZEN and without the administration of mycotoxin binders, while
      positive control group (C+) was exposed to 0.1 mg/mouse/day ZEN and without the
      provision of mycotoxin binders. Treatment groups (T1, T2, T3) were exposed to 0.1
      mg/mouse/day ZEN and mycotoxin binders 0.5; 1; 2 mg/BW/day. RESULTS: ZEN and
      mycotoxin binders administration was conducted for 10 days. The number of primary
      follicles, secondary, tertiary, de Graaf's follicles and CL in negative control
      (C-) was 14.2+/-1.36, 11.2+/-0.28, 6.5+/-0.53, 7.5+/-0.74, and 2.3+/-0.35. The
      number in positive control (C+) group was as follows 7.1+/-0.12, 3.7+/-1.17,
      3.8+/-1.21, 1.5+/-0.62, and 2.3+/-0.34. Results in treatment 1 (T1) were as
      follows 6.2+/-0.16, 5.2+/-0.16, 3.6+/-0.16, 2.6+/-0.19, and 2.6+/-0.10; in
      treatment 2 (T2) 7.8+/-0.28, 5.8+/-0.53, 3.7+/-0.26, 2.7+/-0.26, and 2.5+/-0.10;
      and in treatment 3 (T3) 8.4+/-0.34, 8.4+/-0.34, 4.6+/-0.34, 4.5+/-1.01, and 3.4+/
      0.23. CONCLUSION: The number of follicles and CL more in line with increasing
      doses of mycotoxin binders. Required more than 2 mg/mouse/day mycotoxin binders
      to inhibit the effects of ZEN so that its can maintain the number of primary
      follicle, secondary follicle, tertiary follicle, the de Graaf's follicle, and the
      number of CL in the ovary of ZEN-exposed female mice (Mus musculus).

PMID- 28435201
TI  - Association of claw disorders with subclinical intramammary infections in
      Egyptian dairy cows.
AB  - AIM: Bovine mastitis and lameness are the most common production diseases
      affecting dairy farms worldwide resulting in huge economic impact and impaired
      animal welfare. The objective of this field study was to investigate the
      association of infectious and non-infectious claw disorders with the occurrence
      of subclinical intramammary infections (IMIs) diagnosed by California mastitis
      test (CMT) in dairy cows under Egyptian conditions. MATERIALS AND METHODS: A
      total of 43 dairy cows were included in this field study. Subclinical IMI was
      diagnosed by CMT on all lactating quarters of cows. A cow was considered to have
      subclinical IMI if it had at least one subclinically infected quarter (>=3). Cows
      were inspected carefully for claw disorders that recorded based on type and site.
      Locomotion and body condition scores were also recorded for each cow in addition
      to the limb affected. The association between the CMT and other explanatory
      variables was tested by Fisher's exact test. RESULTS: The prevalence of
      infectious and non-infectious claw disorders was 81.4% (35/43) and 32.6% (14/43),
      respectively. Digital dermatitis (DD) and heel horn erosion were the most
      prevalent infectious type with 79% (34/43) and 58% (25/43), respectively, while
      wall fissure was the most identified non-infectious one 11.6% (5/43). The
      prevalence of claw disorders in hind limbs was 88.4% (38/43) and 11.6% (5/43) in
      the forelimbs. Infectious claw disorders were significantly associated with the
      subclinical IMI diagnosed by CMT (p<0.05). Non-infectious claw affections,
      locomotion score, body condition score, and the affected limb had no association
      with the occurrence of subclinical IMI. CONCLUSION: DD is the highest prevalent
      claw disorder observed in dairy cows in Egypt. The hind limbs are more
      susceptible to claw disorders than the forelimbs. Infectious type of claw
      disorders is significantly associated with subclinical IMI diagnosed by CMT in
      dairy cows under Egyptian conditions indicating that the infectious types of claw
      affections may influence the udder health.

PMID- 28435203
TI  - Dai-Kou type conjugate gradient methods with a line search only using gradient.
AB  - In this paper, the Dai-Kou type conjugate gradient methods are developed to solve
      the optimality condition of an unconstrained optimization, they only utilize
      gradient information and have broader application scope. Under suitable
      conditions, the developed methods are globally convergent. Numerical tests and
      comparisons with the PRP+ conjugate gradient method only using gradient show that
      the methods are efficient.

PMID- 28435202
TI  - Phenotypic and genotypic characterization of methicillin-resistant Staphylococcus
      aureus from bovine mastitis.
AB  - AIM: This study was conducted to determine the occurrence of methicillin
      sensitive and Staphylococcus aureus (MSSA) methicillin-resistant S. aureus (MRSA)
      from bovine mastitis and to characterize them with respect to antibiotic
      resistance gene mecA. MATERIALS AND METHODS: A total of 160 mastitic milk samples
      were screened for the presence of S. aureus. The presumptive positive isolates
      were confirmed using nuc and 23S rRNA gene-based polymerase chain reaction. All
      the confirmed isolates were subjected to in vitro antibiogram using a number of
      antibiotics. Isolates which showed resistance against methicillin were
      characterized for the presence of mecA gene. RESULTS: Out of the total 160 milk
      samples, 36 (22.5%) samples yielded S. aureus. The in vitro antibiogram revealed
      that 16.6% S. aureus isolates were resistant to all antibiotics screened for and
      5.5% isolates were sensitive to all of them. Furthermore, the study found 94.4%,
      83.3%, 77.7%, 66.6%, 50%, and 27.7% of S. aureus isolates resistant to
      penicillin, ampicillin, amoxicillin-sulbactam, enrofloxacin, ceftriaxone, and
      methicillin, respectively. Out of the 36 S. aureus isolates, only 6 (16.6%)
      isolates were confirmed as MRSA while rest were MSSA. CONCLUSION: The higher
      occurrence of S. aureus-mediated mastitis was concluded due to improper hygienic
      and poor farm management. The multiple drug resistance reveals the indiscriminate
      use of drugs and presence of methicillin resistance gene determinant is an
      alarming situation as such infections are difficult to treat.

PMID- 28435204
TI  - Bounds for the norm of lower triangular matrices on the Cesaro weighted sequence
      space.
AB  - This paper is concerned with the problem of finding bounds for the norm of lower
      triangular matrix operators from [Formula: see text] into [Formula: see text],
      where [Formula: see text] is the Cesaro weighted sequence space and [Formula: see
      text] is a non-negative sequence. Also this problem is considered for lower
      triangular matrix operators from [Formula: see text] into [Formula: see text],
      and the norms of certain matrix operators such as Cesaro, Norlund and weighted
      mean are computed.

PMID- 28435205
TI  - The disc separation and the eigenvalue distribution of the Schur complement of
      nonstrictly diagonally dominant matrices.
AB  - The result on the Gersgorin disc separation from the origin for strictly
      diagonally dominant matrices and their Schur complements in (Liu and Zhang in
      SIAM J. Matrix Anal. Appl. 27(3):665-674, 2005) is extended to nonstrictly
      diagonally dominant matrices and their Schur complements, showing that under some
      conditions the separation of the Schur complement of a nonstrictly diagonally
      dominant matrix is greater than that of the original grand matrix. As an
      application, the eigenvalue distribution of the Schur complement is discussed for
      nonstrictly diagonally dominant matrices to derive some significant conclusions.
      Finally, some examples are provided to show the effectiveness of theoretical
      results.

PMID- 28435206
TI  - New progress on the operator inequalities involving improved Young's and its
      reverse inequalities relating to the Kantorovich constant.
AB  - The purpose of this paper is to give a survey of the progress, advantages and
      limitations of various operator inequalities involving improved Young's and its
      reverse inequalities related to the Kittaneh-Manasrah inequality. We also present
      our new progress to the related research topics. New scalar versions of Young's
      inequalities are promoted, the operator version and the Hilbert-Schmidt form also
      get a promotion.

PMID- 28435207
TI  - Simultaneous feedback control of plasma rotation and stored energy on NSTX-U
      using neoclassical toroidal viscosity and neutral beam injection.
AB  - A model-based feedback system is presented enabling the simultaneous control of
      the stored energy through betan and the toroidal rotation profile of the plasma
      in National Spherical Torus eXperiment Upgrade device. Actuation is obtained
      using the momentum from six injected neutral beams and the neoclassical toroidal
      viscosity generated by applying three-dimensional magnetic fields. Based on a
      model of the momentum diffusion and torque balance, a feedback controller is
      designed and tested in closed-loop simulations using TRANSP, a time dependent
      transport analysis code, in predictive mode. Promising results for the ongoing
      experimental implementation of controllers are obtained.

PMID- 28435208
TI  - Is high myopia a risk factor for visual field progression or disk hemorrhage in
      primary open-angle glaucoma?
AB  - PURPOSE: The purpose of this study was to clarify differences between highly
      myopic and non-myopic primary open-angle glaucoma (POAG) patients, including
      normal-tension glaucoma patients. PATIENTS AND METHODS: A total of 269 POAG
      patients were divided into two groups: patients with >=26.5 mm of axial length
      (highly myopic group) and patients with <24.0 mm of axial length (non-myopic
      group). RESULTS: We analyzed 53 highly myopic and 93 non-myopic POAG patients.
      Age at first visit of the highly myopic group was significantly less than that of
      the non-myopic group (P<0.0001). Baseline intraocular pressures (IOPs) showed no
      significant differences. Follow-up IOPs of the non-myopic group were
      significantly lower than those of the highly myopic group (P=0.0009). According
      to the mean deviation definition of progression, the cumulative probability of
      non-progression of visual field (VF) loss was significantly greater in the highly
      myopic group (10-year survival rate, 73.7%+/-6.8%) than in the non-myopic group
      (10-year survival rate, 46.3%+/-5.8%; log-rank test, P=0.0142). The occurrence of
      disk hemorrhage (DH) in the non-myopic group (1.60+/-3.04) was significantly
      greater than that in the highly myopic group (0.93+/-2.13, P=0.0311). The
      cumulative probability of DH was significantly lower in the highly myopic group
      (10-year survival rate, 26.4%+/-5.4%) than in the non-myopic group (10-year
      survival rate, 47.2%+/-6.6%, P=0.0413). CONCLUSION: Highly myopic POAG is
      considered as a combination of myopic optic neuropathy and glaucomatous optic
      neuropathy (GON). If GON is predominant, it has frequent DH and more progressive
      VF loss. However, when the myopic optic neuropathy is predominant, it has less DH
      and less progressive VF loss.

PMID- 28435209
TI  - Increase in average foveal thickness after internal limiting membrane peeling.
AB  - PURPOSE: To report the findings in three cases in which the average foveal
      thickness was increased after a thin epiretinal membrane (ERM) was removed by
      vitrectomy with internal limiting membrane (ILM) peeling. METHODS: The foveal
      contour was normal preoperatively in all eyes. All cases underwent successful
      phacovitrectomy with ILM peeling for a thin ERM. The optical coherence tomography
      (OCT) images were examined before and after the surgery. The changes in the
      average foveal (1 mm) thickness and the foveal areas within 500 MUm from the
      foveal center were measured. The postoperative changes in the inner and outer
      retinal areas determined from the cross-sectional OCT images were analyzed.
      RESULTS: The average foveal thickness and the inner and outer foveal areas
      increased significantly after the surgery in each of the three cases. The
      percentage increase in the average foveal thickness relative to the baseline
      thickness was 26% in Case 1, 29% in Case 2, and 31% in Case 3. The percentage
      increase in the foveal inner retinal area was 71% in Case 1, 113% in Case 2, and
      110% in Case 3, and the percentage increase in foveal outer retinal area was 8%
      in Case 1, 13% in Case 2, and 18% in Case 3. CONCLUSION: The increase in the
      average foveal thickness and the inner and outer foveal areas suggests that a
      centripetal movement of the inner and outer retinal layers toward the foveal
      center probably occurred due to the ILM peeling.

PMID- 28435210
TI  - Incidence of interface fluid syndrome after laser in situ keratomileusis in
      Egyptian patients.
AB  - PURPOSE: To determine the incidence of interface fluid syndrome (IFS) secondary
      to steroid-induced elevation of intraocular pressure (IOP) following laser in
      situ keratomileusis (LASIK) in myopic Egyptian patients. METHODS: This
      retrospective case series study was conducted at El-Gowhara Private Eye Center.
      The medical records of 1,807 patients (3,489 eyes), who underwent LASIK to
      correct myopia from April 2012 to December 2015 were included. The patients were
      operated on and reviewed by one surgeon (AAG) for IFS after LASIK associated with
      elevation of IOP (as compared to preoperative values). RESULTS: This paper
      reports the incidence of 2.9% (54 patients) (102 eyes) of IFS induced by
      increased IOP after LASIK in Egyptian patients. The medical records of 1,807
      patients (3,489 eyes) with mean age +/- standard deviation (SD) 26.4+/-2.7 years,
      who presented with mean myopia +/- SD -4.50+/-1.3 D, mean astigmatism +/- SD 
      1.43+/-0.8, mean IOP +/- SD 15.2+/-1.2 mmHg, and mean central corneal thickness
      +/- SD 549+/-25.6 MUm, were included. The preoperative anterior and posterior
      segments, corneal topography, and Schirmer's test were unremarkable. CONCLUSION:
      Limiting topical steroids and routinely measuring the IOP post-LASIK are
      necessary steps to prevent IFS, especially in case of myopia. A high index of
      suspicion is required to make a diagnosis. High-resolution optical coherence
      tomography is helpful to confirm the diagnosis.

PMID- 28435211
TI  - Erratum: Prolongation of injection interval after switching therapy from
      ranibizumab to aflibercept in Japanese patients with macular edema secondary to
      branch retinal vein occlusion [Corrigendum].
AB  - [This corrects the article on p. 403 in vol. 11, PMID: 28260852.].

PMID- 28435212
TI  - Testing the clinical value of multifocal electroretinography and microperimetry
      and the effects of intravitreal therapy with ranibizumab on macular function in
      the course of wet age-related macular degeneration: a 1-year prospective study.
AB  - PURPOSE: To investigate the clinical value of multifocal electroretinography
      (mfERG) and microperimetry and the effects of intravitreal therapy with
      ranibizumab (Lucentis(r)) on macular function in the course of neovascular age
      related macular degeneration (nAMD). MATERIALS AND METHODS: We conducted a
      prospective single-arm interventional cohort study with 20 nAMD patients older
      than 50 years. Examinations were scheduled monthly for 1 year during intravitreal
      therapy with ranibizumab. The examinations included mfERG, microperimetry,
      spectral domain optical coherence tomography, and best-corrected visual acuity
      using ETDRS score. RESULTS: During the 12-month observation period, a significant
      positive linear correlation between the logarithm of minimum angle of resolution
      (logMAR) and scotoma area (r=0.28, 95% confidence interval [CI] 0.21-0.35),
      between logMAR and fovea thickness in optical coherence tomography (r=0.11, 95%
      CI 0.04-0.2), and a significant negative correlation between logMAR and mfERG (
      0.37, 95% CI -0.43 to -0.31) were observed. A significant ranibizumab effect on
      logMAR was found (P=0.0065). From a total of 25 relapses, 14 were able to be
      predicted correctly by mfERG P1 decrease in the preceding month. However, there
      was no statistically significant relation between prediction and observed
      relapses (Fisher's exact test, P=0.6726). CONCLUSION: Our results indicate a
      possible role of mfERG and microperimetry in the monitoring of macular function
      and prediction of recurrence during intravitreal pharmacotherapy in wet AMD.

PMID- 28435213
TI  - Comparison of 0.2% and 0.18% hyaluronate eye drops in patients with moderate to
      severe dry eye with keratitis or keratoconjunctivitis.
AB  - PURPOSE: Comparison of efficacy and safety of 0.2% and 0.18% hyaluronic acid (HA)
      eye drops three times a day (tid) in patients with moderate to severe dry eye
      disease, related to keratitis or keratoconjunctivitis. PATIENTS AND METHODS:
      Prospective, multicenter, randomized, single-masked, phase IIIb, noninferiority
      study (0.2% HA vs 0.18% HA) in two parallel groups over a period of 84 days. N=70
      patients were evaluated. Primary efficacy outcome was ocular surface (OS)
      staining change on day 35 (D35), compared to baseline. Fluorescein and lissamine
      green were used for staining of cornea and conjunctiva. Secondary efficacy
      outcome included tear film breakup time, OS staining score on day 84 (D84),
      ocular comfort index, as well as patients' and doctors' evaluation. RESULTS:
      Compared to day 0 (D0), 0.2% HA achieved a 47.7% reduction in staining score (
      3.00+/-2.81 [standard deviation] points, n=38 patients) at D35; 0.18% HA showed a
      41.2% reduction (-2.59+/-2.20 [standard deviation] points, n=32 patients).
      Statistical analysis showed noninferiority in efficacy of 0.2% HA compared to
      0.18% HA on D35. At D84, the reduction in staining score had further increased to
      64.5% for 0.2% HA and to 56.4% for 0.18% HA. Both eye drops improved tear film
      breakup time and ocular comfort index values. Investigators and patients assessed
      both treatments with 5 of 7 points (Likert Scale, medians). The rate of adverse
      events (AE) was 2.3% for 0.2% HA and 7.1% for 0.18% HA with no serious AE.
      CONCLUSION: 0.2% and 0.18% HA eye drops significantly improved signs and symptoms
      of dry eye disease and were well tolerated with few AEs. Noninferiority of 0.2%
      HA compared to 0.18% HA was demonstrated for reduction of OS lesions. In some
      parameters, there was a nonsignificant trend in favor of 0.2% HA concentration.

PMID- 28435214
TI  - Immediate sequential bilateral intravitreal injections: an Indian perspective.

PMID- 28435215
TI  - A comparison of mesopic visual acuity and objective visual quality following
      cataract surgery with hydrophobic acrylic intraocular lenses.
AB  - PURPOSE: To evaluate mesopic visual acuity and visual quality as measured by
      objective scatter index (OSI) in pseudophakic eyes with long-term follow-up after
      implantation of hydrophobic acrylic lenses made from two different lens
      materials. SETTING: This study was carried out in a private clinic. DESIGN: This
      study was an observational cohort study. METHODS: This pilot study included 181
      eyes of 136 patients who had undergone cataract surgery with implantation of
      monofocal hydrophobic acrylic intraocular lenses (IOLs), either Alcon AcrySof (82
      eyes) or Abbott Medical Optics' Tecnis (99 eyes). The monocular corrected
      distance visual acuity (CDVA) of the subjects was recorded under mesopic room
      illumination and OSI was measured by an optical quality analysis system using
      double-pass wavefront method. RESULTS: Mean follow-up duration was 60.07+/-18.82
      months. Eyes implanted with Tecnis IOLs had statistically significantly better
      mesopic CDVA (0.08+/-0.08) compared to those implanted with AcrySof IOLs (0.11+/
      0.07) (P=0.020). Mesopic CDVA of 20/25 or better was found in 79.8% of eyes in
      the Tecnis group compared to 62.2% of eyes in AcrySof group. Similarly, OSI was
      also found to be statistically significantly better for Tecnis IOLs compared to
      AcrySof IOL group (mean OSI, Tecnis: 1.65+/-0.92, AcrySof: 2.01+/-1.36; P=0.033).
      When glaucomatous eyes were excluded, OSI was still significantly better
      (P=0.028) in the Tecnis IOL group. CONCLUSION: The eyes implanted with Tecnis
      IOLs showed better long-term optical performance in terms of both OSI and mesopic
      visual acuity in comparison to those with AcrySof IOLs.

PMID- 28435216
TI  - Pain perception description after advanced surface ablation.
AB  - PURPOSE: The objective of this study was to characterize the evolution of ocular
      pain after advanced surface ablation (ASA) to improve strategies in postoperative
      pain management. METHODS: This was a multicenter, prospective, descriptive,
      cohort study. The inclusion criteria were healthy individuals >=18 years old
      receiving bilateral alcohol-assisted surface ablation with epithelial removal.
      Pain intensity was evaluated with the visual analog scale (VAS) and the numeric
      pain rating scale before and after surgery. Comorbidities (photophobia, burning,
      tearing, and foreign body sensation) and Hospital Anxiety and Depression (HAD)
      questionnaire were evaluated before and at 6 hours after surgery. Postoperative
      treatments included cold patch, topical cold antibiotics, topical steroids, and
      benzodiazepines. RESULTS: Thirty-two consecutive patients having similar profiles
      of postoperative pain evolution were included. At 0.5 hour after ASA, the pain
      score by VAS was 37+/-20 mm, and the maximum pain, 61+/-31 mm, occurred at 24
      hours. Afterward, it decreased progressively until 72 hours after surgery (19+/
      20 mm). Most patients (81%) scored >60 mm, and 44% required rescue medication.
      Among the comorbidities, all patients had photophobia and 84% had burning
      sensation. At 6 hours, the HAD score was 5.4+/-3.9, within the range of values
      considered as normal. CONCLUSION: Postoperative acute ocular pain after ASA
      showed a characteristic evolution over time. Recognition of the pattern could be
      important for improving the acceptance of ASA and for improving strategies in
      pain management in the postoperative period.

PMID- 28435218
TI  - Pharmacokinetics and safety of olopatadine hydrochloride 0.77% in healthy
      subjects with asymptomatic eyes: data from 2 independent clinical studies.
AB  - PURPOSE: To assess the pharmacokinetics and safety of hydrochloride ophthalmic
      solution 0.77% olopatadine from 2 independent (Phase I and Phase III,
      respectively) clinical studies in healthy subjects. MATERIALS AND METHODS: The
      Phase I, multicenter, randomized (2:1), vehicle-controlled study was conducted in
      subjects >=18 years old (N=36) to assess the systemic pharmacokinetics of
      olopatadine 0.77% following single- and multiple-dose exposures. The Phase III,
      multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects
      >=2 years old (N=499) to evaluate long-term ocular safety of olopatadine 0.77%.
      Subjects received olopatadine 0.77% or vehicle once daily bilaterally for 7 days
      in the pharmacokinetic study and 6 weeks in the safety study. RESULTS: In the
      pharmacokinetic study, olopatadine 0.77% was absorbed slowly and reached a peak
      plasma concentration (Cmax) of 1.65 ng/mL following single-dose and 1.45 ng/mL
      following multiple-dose exposures in 2 hours (time to reach maximum plasma
      concentration [Tmax]). After reaching peak concentrations, olopatadine showed a
      similar mono-exponential decay following single and multiple doses with mean
      elimination half-life ranging from 2.90 to 3.40 hours. No accumulation in
      olopatadine exposure (Cmax and area under the plasma concentration-time curve
      from 0 to 12 hours) was evident after multiple doses when compared to single
      dose. In the safety study, treatment-emergent adverse events were reported in
      26.7% and 31.4% of subjects with olopatadine 0.77% and vehicle, respectively.
      Blurred vision was the most frequent ocular treatment-emergent adverse event in
      both treatment groups (olopatadine 0.77% vs vehicle, 4.8% vs 4.1%). No deaths or
      serious adverse events were reported during the study. CONCLUSION: Olopatadine
      0.77% had minimal systemic exposure or accumulation in healthy subjects and was
      well tolerated in both adult and pediatric subjects.

PMID- 28435217
TI  - Patient selection for corneal collagen cross-linking: an updated review.
AB  - Corneal cross-linking (CXL) is an option that in the last decade has demonstrated
      its efficacy and safety in halting the progression of keratoconus (KCN) and other
      corneal ectasias. Its indication has been extended beyond the classic definition
      that required evidence of KCN progression, especially in the presence of some
      risk factors for a possible progression (particularly the younger age). However,
      the results can be still somewhat variable today. There are several protocols,
      each with its own advantages and disadvantages. Some predictors of CXL outcome
      have been identified. We will review the current knowledge on patient selection
      for CXL, its indications, and options in special cases (such as thin corneas).

PMID- 28435219
TI  - Clinical effectiveness of currently available low-vision devices in glaucoma
      patients with moderate-to-severe vision loss.
AB  - PURPOSE: The aim of this trial is to study the effectiveness of currently
      available low-vision devices in glaucoma patients with moderate-to-severe vision
      loss. DESIGN: This is a randomized pilot clinical trial. PARTICIPANTS: Sixteen
      low-vision glaucoma patients participated in this study. METHODS: Patients with a
      best-corrected visual acuity between 20/70 and 20/400 in the better eye and a
      diagnosis of stable primary or secondary open-angle glaucoma were randomized to a
      low-vision treatment group or a nonintervention control group. A telephone
      interview was conducted before and after the 4-week testing period to assess
      functional vision. Patients placed in the treatment group received a low-vision
      examination and used various currently available low-vision aids. Patients placed
      in the control group received a low-vision examination only. Changes in patients'
      reading ability and overall visual ability were chosen as the primary outcomes.
      Other visual functioning domains (mobility, visual information processing and
      visual motor skills) were considered as secondary outcomes. RESULTS: Ten patients
      in the treatment group showed a significant improvement in reading ability and
      overall visual ability compared to the control group. The difference in mean
      score for reading ability was 2.52 logits (2.02; P<0.05) and overall visual
      ability was 0.78 logits (0.64; P<0.05). However, no significant improvement was
      noted in the other visual functioning domains involving mobility and visual motor
      skills. CONCLUSION: Currently available low-vision devices primarily enhance
      central vision with limited benefits to functional activities relying on
      peripheral vision.

PMID- 28435220
TI  - Formulation, release characteristics, and bioavailability study of
      gastroretentive floating matrix tablet and floating raft system of Mebeverine
      HCl.
AB  - To prolong the residence time of dosage forms within the gastrointestinal tract
      until all drug is released at the desired rate is one of the real challenges for
      oral controlled-release drug delivery systems. This study was designed to develop
      a controlled-release floating matrix tablet and floating raft system of
      Mebeverine HCl (MbH) and evaluate different excipients for their floating
      behavior and in vitro controlled-release profiles. Oral pharmacokinetics of the
      optimum matrix tablet, raft system formula, and marketed Duspatalin(r) 200 mg
      retard as reference were studied in beagle dogs. The optimized tablet formula (FT
      10) and raft system formula (FRS-11) were found to float within 34+/-5 sec and
      15+/-7 sec, respectively, and both remain buoyant over a period of 12 h in
      simulated gastric fluid. FT-10 (Compritol/HPMC K100M 1:1) showed the slowest drug
      release among all prepared tablet formulations, releasing about 80.2% of MbH over
      8 h. In contrast, FRS-11 (Sodium alginate 3%/HPMC K100M 1%/Precirol 2%) had the
      greatest retardation, providing sustained release of 82.1% within 8 h. Compared
      with the marketed MbH product, the Cmax of FT-10 was almost the same, while FRS
      11 maximum concentration was higher. The tmax was 3.33, 2.167, and 3.0 h for
      marketed MbH product, FT-10, and FRS-11, respectively. In addition, the oral
      bioavailability experiment showed that the relative bioavailability of the MbH
      was 104.76 and 116.01% after oral administration of FT-10 and FRS-11,
      respectively, compared to marketed product. These results demonstrated that both
      controlled-released floating matrix tablet and raft system would be promising
      gastroretentive delivery systems for prolonging drug action.

PMID- 28435221
TI  - Phenotypic evaluation and in silico ADMET properties of novel arylimidamides in
      acute mouse models of Trypanosoma cruzi infection.
AB  - Arylimidamides (AIAs), previously termed as reversed amidines, present a broad
      spectrum of activity against intracellular microorganisms. In the present study,
      three novel AIAs were evaluated in a mouse model of Trypanosoma cruzi infection,
      which is the causative agent of Chagas disease. The bis-AIAs DB1957, DB1959 and
      DB1890 were chosen based on a previous screening of their scaffolds that revealed
      a very promising trypanocidal effect at nanomolar range against both the
      bloodstream trypomastigotes (BTs) and the intracellular forms of the parasite.
      This study focused on both mesylate salts DB1957 and DB1959 besides the
      hydrochloride salt DB1890. Our current data validate the high activity of these
      bis-AIA scaffolds that exhibited EC50 (drug concentration that reduces 50% of the
      number of the treated parasites) values ranging from 14 to 78 nM and 190 to 1,090
      nM against bloodstream and intracellular forms, respectively, also presenting
      reasonable selectivity indexes and no mutagenicity profile predicted by in silico
      absorption, distribution, metabolism, excretion, and toxicity (ADMET). Acute
      toxicity studies using murine models revealed that these AIAs presented only mild
      toxic effects such as reversible abdominal contractions and ruffled fur. Efficacy
      assays performed with Swiss mice infected with the Y strain revealed that the
      administration of DB1957 for 5 consecutive days, with the first dose given at
      parasitemia onset, reduced the number of BTs at the peak, ranging between 21 and
      31% of decrease. DB1957 was able to provide 100% of animal survival, while
      untreated animals showed 70% of mortality rates. DB1959 and DB1890B did not
      reduce circulating parasitism but yielded >80% of survival rates.

PMID- 28435222
TI  - Effects of intrathecal dexmedetomidine on shivering after spinal anesthesia for
      cesarean section: a double-blind randomized clinical trial.
AB  - BACKGROUND: Shivering is among the common troublesome complications of spinal
      anesthesia (SA), and causes discomfort and discontentment in parturients
      undergoing cesarean sections (CSs). The aim of this study was to investigate the
      effects of intrathecal dexmedetomidine in the prevention of shivering in those
      who underwent CS under SA. SUBJECTS AND METHODS: Fifty parturients planned for
      elective CSs under SA were enrolled in this prospective, double-blinded,
      controlled study and randomly divided into two equal groups. Spinal block was
      achieved with 12.5 mg 0.5% heavy bupivacaine plus 5 MUg dexmedetomidine (BD
      group) or 0.5 mL 0.9% normal saline (BN group). The incidence and intensity of
      shivering, peripheral and core body temperature, hemodynamic parameters, and
      adverse events was recorded. RESULTS: The incidence of shivering was
      significantly higher in the BN group (52%) than the BD group (24%) (P=0.04).
      Likewise, the intensity of shivering was significantly higher in the BN group
      than the BD group (P=0.04). The incidence of adverse events, such as hypotension,
      nausea/vomiting, and bradycardia, was not significantly different between the two
      groups, although the grade of sedation was higher in the BD group than the BN
      group (P=0.004). CONCLUSION: We conclude that intrathecal dexmedetomidine is
      effective in lowering the incidence and intensity of shivering in parturients
      undergoing CSs under SA without major adverse effects.

PMID- 28435223
TI  - Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with
      imatinib mesylate against chronic myelogenous leukemia cell lines.
AB  - BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin
      (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the
      effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and
      autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine
      kinase inhibitor in vitro. METHODS: Two human CML cell lines, K562 and KBM7R
      (T315I mutant strain), were used. The proliferation of CML cells was detected by
      MTS (Owen's reagent) assay. Cell cycle and apoptosis assay were examined by flow
      cytometric analysis. The phosphorylation levels and the expression levels were
      both evaluated by Western blot analysis. NVP-BEZ235 in combination with imatinib
      was also used to reveal the effect on proliferation and apoptosis. RESULTS: NVP
      BEZ235 significantly inhibited the proliferation in a time- and dose-dependent
      manner, and the half-maximal inhibitory concentration values of NVP-BEZ235
      inhibiting the proliferation of K562 and KBM7R were 0.37+/-0.21 and 0.43+/-0.27
      MUmol/L, respectively, after 48 h. Cell apoptosis assay showed that NVP-BEZ235
      significantly increased the late apoptotic cells. Cell cycle analysis indicated
      that the cells were mostly arrested in G1/G0 phase after treatment by NVP-BEZ235.
      In addition, results also found that, after treatment by NVP-BEZ235,
      phosphorylation levels of Akt kinase and S6K kinase significantly reduced, and
      the expression levels of cleaved caspase-3 significantly increased; meanwhile,
      the expression levels of caspase-3, B-cell lymphoma-2, cyclin D1, and cyclin D2
      significantly decreased, and the ratio of LC3II/LC3I was significantly increased
      with increased LC3II expression level. Moreover, imatinib in combination with NVP
      BEZ235 induced a more pronounced colony growth inhibition than imatinib alone.
      CONCLUSION: NVP-BEZ235 effectively inhibited cell proliferation by G0/G1 cell
      cycle arrest and induced apoptosis through deregulating PI3K/Akt/mTOR pathway in
      CML cells; in addition, NVP-BEZ235 can enhance cell autophagy, and is conducive
      to raising CML cell sensitivity to imatinib to inhibit the growth of imatinib
      resistant cells.

PMID- 28435224
TI  - Investigation of triamterene as an inhibitor of the TGR5 receptor: identification
      in cells and animals.
AB  - BACKGROUND: G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5)
      has been shown to participate in glucose homeostasis. In animal models, a TGR5
      agonist increases incretin secretion to reduce hyperglycemia. Many agonists have
      been developed for clinical use. However, the effects of TGR5 blockade have not
      been studied extensively, with the exception of studies using TGR5 knockout mice.
      Therefore, we investigated the potential effect of triamterene on TGR5. METHODS:
      We transfected the TGR5 gene into cultured Chinese hamster ovary cells (CHO-K1
      cells) to express TGR5. Then, we applied a fluorescent indicator to examine the
      glucose uptake of these transfected cells. In addition, NCI-H716 cells that
      secrete incretin were also evaluated. Fura-2, a fluorescence indicator, was
      applied to determine the changes in calcium concentrations. The levels of cyclic
      adenosine monophosphate (cAMP) and glucagon-like peptide (GLP-1) were estimated
      using enzyme-linked immunosorbent assay kits. Moreover, rats with streptozotocin
      (STZ)-induced type 1-like diabetes were used to investigate the effects in vivo.
      RESULTS: Triamterene dose dependently inhibits the increase in glucose uptake
      induced by TGR5 agonists in CHO-K1 cells expressing the TGR5 gene. In cultured
      NCI-H716 cells, TGR5 activation also increases GLP-1 secretion by increasing
      calcium levels. Triamterene inhibits the increased calcium levels by TGR5
      activation through competitive antagonism. Moreover, the GLP-1 secretion and
      increased cAMP levels induced by TGR5 activation are both dose dependently
      reduced by triamterene. However, treatment with KB-R7943 at a dose sufficient to
      block the Na+/Ca2+ exchanger (NCX) failed to modify the responses to TGR5
      activation in NCI-H716 cells or CHO-K1 cells expressing TGR5. Therefore, the
      inhibitory effects of triamterene on TGR5 activation do not appear to be related
      to NCX inhibition. Blockade of TGR5 activation by triamterene was further
      characterized in vivo using the STZ-induced diabetic rats. CONCLUSION: Based on
      the obtained data, we identified triamterene as a reliable inhibitor of TGR5.
      Therefore, triamterene can be developed as a clinical inhibitor of TGR5
      activation in future studies.

PMID- 28435225
TI  - Association of genetic variations with pharmacokinetics and lipid-lowering
      response to atorvastatin in healthy Korean subjects.
AB  - BACKGROUND: Statins are effective agents in the primary and secondary prevention
      of cardiovascular disease, but treatment response to statins varies among
      individuals. We analyzed multiple genetic polymorphisms and assessed
      pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment
      in healthy Korean individuals. METHODS: Atorvastatin 80 mg was given to 50
      healthy Korean male volunteers. Blood samples were collected to measure plasma
      atorvastatin and lipid concentrations up to 48 hours after atorvastatin
      administration. Subjects were genotyped for 1,936 drug metabolism and transporter
      genetic polymorphisms using the Affymetrix DMET plus array. RESULTS: The
      pharmacokinetics and lipid-lowering effect of atorvastatin showed remarkable
      interindividual variation. Three polymorphisms in the SLCO1B1, SLCO1B3, and ABCC2
      genes were associated with either the maximum concentration (Cmax) of
      atorvastatin or changes in total cholesterol or low-density lipoprotein
      cholesterol (LDL-C). Minor homozygotes (76.5 ng/mL) of SLCO1B1 c.-910G>A showed
      higher Cmax than heterozygotes (34.0 ng/mL) and major homozygotes (33.5 ng/mL,
      false discovery rate P=0.040). Cmax and the area under the plasma concentration
      curve from hour 0 to infinity (AUCinfinity) were higher in carriers of the
      SLCO1B1*17 haplotype that included c.-910G>A than in noncarriers (46.1 vs 32.8
      ng/mL for Cmax; 221.5 vs 154.2 ng/mL for AUCinfinity). SLCO1B3 c.334G>T
      homozygotes (63.0 ng/mL) also showed higher Cmax than heterozygotes (34.7 ng/mL)
      and major homozygotes (31.4 ng/mL, FDR P=0.037). A nonsynonymous ABCC2 c.1249G>A
      was associated with small total cholesterol and LDL-C responses (0.23% and -0.70%
      for G/A vs -11.9% and -17.4% for G/G). The Cmax tended to increase according to
      the increase in the number of minor allele of SLCO1B1 c. -910G>A and SLCO1B3
      c.334G>T. CONCLUSION: Genetic polymorphisms in transporter genes, including
      SLCO1B1, SLCO1B3, and ABCC2, may influence the pharmacokinetics and lipid
      lowering response to atorvastatin administration.

PMID- 28435227
TI  - Erratum: Relaxin inhibits cardiac fibrosis and endothelial-mesenchymal transition
      via the Notch pathway [Corrigendum].
AB  - [This corrects the article on p. 4599 in vol. 9.].

PMID- 28435226
TI  - Inhibition of lymphangiogenesis in vitro and in vivo by the multikinase inhibitor
      nintedanib.
AB  - PURPOSE: To investigate the feasibility of nintedanib, a novel triple angiokinase
      inhibitor, for inhibiting lymphatic endothelial cell (LEC)-induced
      lymphangiogenesis in vitro and inflammatory corneal lymphangiogenesis in vivo.
      MATERIALS AND METHODS: Methylthiazolyldiphenyl-tetrazolium bromide (MTT) test,
      transwell system, and tube-formation assay were used to evaluate the effects of
      nintedanib on the proliferation, migration, and tube formation of LECs stimulated
      by vascular endothelial growth factor-C (VEGF-C), basic fibroblast growth factor
      (bFGF), or platelet-derived growth factor-BB (PDGF-BB). The murine model of
      suture-induced corneal neovascularization was used to assess the anti
      hemangiogenic and anti-lymphangiogenic effects of nintedanib via systemic and
      topical applications. Corneal flatmounts were stained with lymphatic vessel
      endothelial hyaluronan receptor-1 (LYVE-1) and CD31, and the areas of involved
      blood and lymph vessels were analyzed morphometrically. Corneal cryosections were
      stained with F4/80 to evaluate inflammatory cell recruitment. RESULTS: We
      observed a significant enhanced effect of LEC proliferation, migration, and tube
      formation with the administration of VEGF-C, PDGF-BB, and bFGF, respectively,
      which was diminished by nintedanib. Both topical and systemic applications of
      nintedanib inhibited suture-induced hemangiogenesis and lymphangiogenesis in the
      murine cornea. A reduction in F4/80+ cell infiltration was observed at day 14
      after corneal suture for both systemic and topical applications of nintedanib. In
      comparison with controls, 61% of F4/80+ cell recruitment was inhibited via the
      systemic application of nintedanib, while 49% of F4/80+ cell recruitment was
      inhibited with the topical application of nintedanib. CONCLUSION: Nintedanib was
      shown to inhibit in vitro lymphangiogenesis stimulated by VEGF-C, bFGF, and PDGF
      BB. Applied topically or systemically, it effectively inhibited corneal
      hemangiogenesis and lymphangiogenesis, accompanied by reduced inflammatory cell
      recruitment, which represents a new promising treatment for graft rejection after
      penetrating keratoplasty.

PMID- 28435228
TI  - Erratum: Decitabine reverses TGF-beta1-induced epithelial-mesenchymal transition
      in non-small-cell lung cancer by regulating miR-200/ZEB axis [Corrigendum].
AB  - [This corrects the article on p. 969 in vol. 11.].

PMID- 28435229
TI  - Medication adherence and persistence in type 2 diabetes mellitus: perspectives of
      patients, physicians and pharmacists on the Spanish health care system.
AB  - OBJECTIVE: A good relationship between diabetes patients and their health care
      team is crucial to ensure patients' medication adherence and self-management. To
      this end, we aimed to identify and compare the views of type 2 diabetes mellitus
      (T2DM) patients, physicians and pharmacists concerning the factors and strategies
      that may be associated with, or could improve, medication adherence and
      persistence. METHODS: An observational, cross-sectional study was conducted using
      an electronic self-administered questionnaire comprising 11 questions (5-point
      Likert scale) concerning factors and strategies related to medication adherence.
      The survey was designed for T2DM patients and Spanish National Health System
      professionals. RESULTS: A total of 963 T2DM patients, 998 physicians and 419
      pharmacists participated in the study. Overall, a lower proportion of pharmacists
      considered the proposed factors associated with medication adherence important as
      compared to patients and physicians. It should be noted that a higher percentage
      of physicians in comparison to pharmacists perceived that "complexity of
      medication" (97% vs 76.6%, respectively) and "adverse events" (97.5% vs 72.2%,
      respectively) were important medication-related factors affecting adherence. In
      addition, both patients (80.8%) and physicians (80.8%) agreed on the importance
      of "cost and co-payment" for adherence, whereas only 48.6% of pharmacists
      considered this factor important. It is also noteworthy that nearly half of
      patients (43%) agreed that "to adjust medication to activities of daily living"
      was the best strategy to reduce therapeutic complexity, whereas physicians
      believed that "reducing the frequency of administration" (47.9%) followed by
      "reducing the number of tablets" (28.5%) was the most effective strategy to
      improve patients' adherence. CONCLUSION: Our results highlight the need for
      pharmacists to build a stronger relationship with physicians in order to improve
      patients monitoring and adherence rates. Additionally, these findings may help to
      incorporate greater patient-centeredness when developing management strategies,
      focusing on adjusting medication regimens to patients' daily lives.

PMID- 28435231
TI  - Complexity of care and strategies of self-management in patients with colorectal
      cancer.
AB  - PURPOSE: Given the inherent complexity of cancer care, in which personal, social,
      and clinical aspects accumulate and interact over time, self-management support
      need to become more comprehensive. This study has the following two aims: 1) to
      analyze and describe the complexity of individual patient situations and 2) to
      analyze and describe already established self-management strategies of patients
      to handle this complexity. METHODS: A qualitative study was conducted. Ten focus
      groups were performed collecting perspectives of the following three user groups:
      patients with colorectal cancer (n=12) and representatives from support groups
      (n=2), physicians (n=17), and other health care professionals (HCPs; n=16). Data
      were analyzed using qualitative content analysis. RESULTS: The results showed
      that cancer patients are struggling with the complexity of their individual
      situations characterized by the 1) "complexity of disease", 2) "complexity of
      care", and 3) "complexity of treatment-related data". To deal with these
      multifaceted situations, patients have established several individual strategies.
      These strategies are "proactive demanding" (eg, to get support and guidance or a
      meaningful dialog with the doctor), "proactive behavior" (eg, preparation of
      visits), and "proactive data management" (eg, in terms of merging treatment
      related data and to disseminate these to their health care providers).
      CONCLUSION: Patients with colorectal cancer have to handle a high complexity of
      individual situations within treatment and care of their disease. Private and
      social challenges have a culminating effect. This complexity increases as
      patients experience a longer duration of treatment and follow-up as patients have
      to handle a significantly higher amount of data over time. Self-management
      support should focus more on the individual complexity in a patient's life. This
      includes assisting patients with strategies that have already been established by
      themselves (like preparation of visits).

PMID- 28435230
TI  - Persistence with golimumab in immune-mediated rheumatic diseases: a systematic
      review of real-world evidence in rheumatoid arthritis, axial spondyloarthritis,
      and psoriatic arthritis.
AB  - PURPOSE: In immune-mediated rheumatic diseases (IMRDs), persistence to treatment
      may be used as a surrogate marker for long-term treatment success. In previous
      comparisons of persistence to tumor necrosis factor alpha inhibitors (TNFis), a
      paucity of data for subcutaneous (SC) golimumab was identified. The aim of this
      study was to conduct a systematic review of persistence to SC golimumab in
      clinical practice and contextualize these data with five-year persistence
      estimates from long-term open-label extension (OLE) trials of SC TNFis in IMRDs.
      PATIENTS AND METHODS: PubMed, Embase, MEDLINE, and conference proceedings from
      European League Against Rheumatism (EULAR), American College of Rheumatology
      (ACR), and International Society for Pharmacoeconomics and Outcomes Research
      (ISPOR) were searched. All studies on patients treated with SC golimumab for IMRD
      were included if they reported data on the persistence to golimumab. RESULTS: Of
      376 available references identified through the searches, 12 studies with a total
      of 4,910 patients met the inclusion criteria. Furthermore, nine OLE trials were
      available. Among the included studies from clinical practice, at six months, one
      year, two years, and three years, the proportion of patients persistent to
      treatment ranged from 63% to 91%, 47% to 80%, 40% to 77%, and 32% to 67%,
      respectively. In the four studies that included comparisons to other biologics,
      golimumab was either statistically noninferior or statistically superior to other
      treatments, an observation that was supported by indirect comparisons of
      unadjusted point estimates of OLE trials. CONCLUSION: The data reviewed in this
      study indicate that golimumab may have higher persistence than other TNFis, a
      notion that is supported by indirect comparisons of persistence data from OLEs of
      randomized controlled trials (RCTs). Furthermore, the study suggests that
      persistence may be lower in biologic-experienced compared with biologic-naive
      patients and higher in axial spondyloarthritis compared with rheumatoid arthritis
      and psoriatic arthritis.

PMID- 28435232
TI  - Self-reported adherence and associated factors to isoniazid preventive therapy
      for latent tuberculosis among people living with HIV/AIDS at health centers in
      Gondar town, North West Ethiopia.
AB  - PURPOSE: This study aimed to assess self-reported adherence and associated
      factors to isoniazid preventive therapy (IPT) for latent tuberculosis among
      people living with HIV/AIDS (PLWHA) at health centers in Gondar town, North West
      Ethiopia. PATIENTS AND METHODS: An institution-based prospective cross-sectional
      study was conducted from March 10 to June 11, 2016. A total of 154 eligible
      participants were included in the study, using the simple random sampling method,
      from the available four health centers and one teaching referral hospital that
      provided antiretroviral therapy (ART) for HIV/AIDS patients. Adherence was
      measured by self-report of isoniazid (INH) tablets taken for the preceding 7
      days. Participants were recruited through in-depth interviews. The collected data
      were entered and analyzed using the statistical packages for social sciences
      (SPSS) version 20. RESULTS: The adherence level to IPT was 90.3% for the last 7
      days of the study. ART was initiated for 84.4%, and all of them were on a first
      line regimen. Isoniazid-related side effects were reported by 48 (31.2%)
      participants, of which the most commonly identified were abdominal pain,
      vomiting, skin rash, jaundice, and numbness. Only 3 (2%) participants
      discontinued from the study. In the bivariate logistic regression analysis,
      respondents who had received an explanation about IPT were 83% times more likely
      to be adherent compared to those who had not received it (95% CI, AOR: 0.266
      [0.23-3.127]). Respondents who had taken IPT for >=5 months were more likely to
      be adherent than those who had taken it for 1-2 months [95% CI, COR: 1.484]. On
      the other hand, respondents who experienced side effects were 36% less likely to
      be adherent compared to those who did not experience any. CONCLUSION: The level
      of adherence to IPT among PLWHA was high. Among the predictors reported,
      carelessness and/or forgetfulness, side effects, and absence from home were the
      major factors identified for being nonadherent. Health professionals and the
      Ministry of Health should design and deliver appropriate health education tips
      and messages. Moreover, counseling of patients who are in their first 2 months of
      therapy should be strengthened further.

PMID- 28435233
TI  - Patient opinions on medicine-use review: exploring an expanding role of community
      pharmacists.
AB  - BACKGROUND: Current evidence supports the benefit of medicine-use review (MUR)
      for the safe and effective use of medicines. However, little is known about
      opinions of consumers regarding their preference for undertaking MUR, especially
      in the developing world, eg, in some Asian countries. We aimed to explore
      patients' opinions about potential MUR and other enhanced services provided by
      community pharmacists. PATIENTS AND METHODS: A qualitative study using focus
      groups was conducted at Naresuan University's community pharmacy, Phitsanulok,
      Thailand. MUR-naive patients were recruited from two pharmacies in Phitsanulok.
      All focus groups were audio-recorded, transcribed, and thematically analyzed.
      RESULTS: Twenty participants attended four focus groups. The following themes
      were identified: 1) requirement and need for the service, 2) accessibility and
      convenience of receiving the service, 3) pharmacist attributes needed in
      delivering the service, and 4) how to promote the use of MUR successfully. The
      majority of participants had poor understanding about their medicines and were
      interested in receiving a MUR service. Regarding accessibility, convenience and
      close proximity of pharmacies to homes were deemed to be supportive of
      participants to use the service. However, several potential barriers to uptake
      were identified: perceived difficulty on the part of recipients in making time to
      receive the service and the inconvenience of having to provide medicines/records
      of medicines to pharmacists. The following domains of pharmacists'
      characteristics were viewed as supportive determinants: personality (friendliness
      and confidence in giving information) and attitude (willingness to provide the
      service and not commercially oriented). The participants suggested that promoting
      the services using a mix of strategies would increase an awareness of MUR
      service. CONCLUSION: Recognizing the unmet needs of patients for information on
      their medicines provides a good opportunity for community pharmacists to offer an
      MUR service to ensure quality use of medicines in the community.

PMID- 28435234
TI  - Strengthening care teams to improve adherence in cystic fibrosis: a qualitative
      practice assessment and quality improvement initiative.
AB  - BACKGROUND: Treatment regimens for patients with cystic fibrosis (CF) are
      complex, time consuming, and burdensome, and adherence to CF treatment is
      suboptimal. CF care teams play a critical role in supporting patients' chronic
      self-management skills, but there is no uniform method for assessing patients'
      adherence to treatment or standard interventions to help patients improve when
      necessary. METHODS: Between May 2015 and March 2016, care team members from 10 CF
      centers in the USA participated in a practice assessment and quality improvement
      (QI) initiative. The intervention included a baseline practice assessment survey,
      personalized continuing medical education (CME)-certified Webconferences with
      expert study faculty, targeted reinforcement of key practice points, and follow
      up online survey and telephone interviews to evaluate the benefits and
      limitations of the intervention. RESULTS: Responses to the baseline practice
      assessment survey were received from 50 multidisciplinary care team members
      representing 10 CF centers. Primary barriers to adherence-related aspects of care
      in their clinics were motivating patients and caregivers to improve adherence and
      obtaining accurate information about adherence from patients. At the conclusion
      of the initiative, participants reported improvements in communication within
      their care team, implementation of new approaches to asking about adherence, and
      a renewed commitment to asking patients and caregivers about adherence at each
      clinic visit. CONCLUSION: Structured QI interventions that bring
      multidisciplinary care teams together to reflect on clinic processes and elicit
      objective insights from outside faculty have the potential to improve practice
      patterns related to the assessment and improvement of patient adherence in CF.

PMID- 28435235
TI  - Age-based model for metacarpophalangeal joint proprioception in elderly.
AB  - Neurological injuries such as stroke can lead to proprioceptive impairment. For
      an informed diagnosis, prognosis, and treatment planning, it is essential to be
      able to distinguish between healthy performance and deficits following the
      neurological injury. Since there is some evidence that proprioception declines
      with age and stroke occurs predominantly in the elderly population, it is
      important to create a healthy reference model in this specific age group.
      However, most studies investigate age effects by comparing young and elderly
      subjects and do not provide a model within a target age range. Moreover, despite
      the functional relevance of the hand in activities of daily living, age-based
      models of distal proprioception are scarce. Here, we present a proprioception
      model based on the assessment of the metacarpophalangeal joint angle difference
      threshold in 30 healthy elderly subjects, aged 55-80 years (median: 63,
      interquartile range: 58-66), using a robotic tool to apply passive flexion
      extension movements to the index finger. A two-alternative forced-choice paradigm
      combined with an adaptive algorithm to define stimulus magnitude was used. The
      mixed-effects model analysis revealed that aging has a significant, increasing
      effect on the difference threshold at the metacarpophalangeal joint, whereas
      other predictors (eg, tested hand or sex) did not show a significant effect. The
      adaptive algorithm allowed reaching an average assessment duration <15 minutes,
      making its clinical applicability realistic. This study provides further evidence
      for an age-related decline in proprioception at the level of the hand. The
      established age-based model of proprioception in elderly may serve as a reference
      model for the proprioceptive performance of stroke patients, or of any other
      patient group with central or peripheral proprioceptive impairments. Furthermore,
      it demonstrates the potential of such automated robotic tools as a rapid and
      quantitative assessment to be used in research and clinical settings.

PMID- 28435236
TI  - Activities-specific balance confidence scale for predicting future falls in
      Indian older adults.
AB  - BACKGROUND: Activities-specific balance confidence (ABC) scale is a subjective
      measure of confidence in performing various ambulatory activities without falling
      or experiencing a sense of unsteadiness. OBJECTIVE: This study aimed to examine
      the ability of the Hindi version of the ABC scale (ABC-H scale) to discriminate
      between fallers and non-fallers and to examine its predictive validity for
      prospective falls. DESIGN: This was a prospective cohort study. MATERIALS AND
      METHODS: A total of 125 community-dwelling older adults (88 were men) completed
      the ABC-H scale. The occurrence of falls over the follow-up period of 12 months
      was recorded. Discriminative validity was analyzed by comparing the total ABC-H
      scale scores between the faller and non-faller groups. A receiver operating
      characteristic curve analysis and a logistic regression analysis were used to
      examine the predictive accuracy of the ABC-H scale. RESULTS: The mean ABC-H scale
      score of the faller group was significantly lower than that of the non-faller
      group (52.6+/-8.1 vs 73.1+/-12.2; P<0.001). The optimal cutoff value for
      distinguishing faller and non-faller adults was <=58.13. The sensitivity,
      specificity, area under the curve, and positive and negative likelihood ratios of
      the cutoff score were 86.3%, 87.3%, 0.91 (P<0.001), 6.84, and 0.16, respectively.
      The percentage test accuracy and false-positive and false-negative rates were
      86.87%, 12.2%, and 13.6%, respectively. A dichotomized total ABC-H scale score of
      <=58.13% (adjusted odds ratio =0.032, 95% confidence interval =0.004-0.25,
      P=0.001) was significantly related with future falls. CONCLUSION: The ABC-H
      scores were significantly and independently related with future falls in the
      community-dwelling Indian older adults. The ability of the ABC-H scale to predict
      future falls was adequate with high sensitivity and specificity values.

PMID- 28435237
TI  - Evaluation of EX-PRESS glaucoma implant in elderly diabetic patients after 23G
      vitrectomy.
AB  - PURPOSE: The most frequent qualifications for pars plana vitrectomy (PPV) in
      diabetic patients include recurrent hemorrhage into the vitreous body chamber and
      vitreoretinal proliferation, also with traction retinal detachment. The aim of
      this study was to evaluate the effectiveness of EX-PRESS implant for the
      treatment of secondary glaucoma in elderly diabetic patients following PPV 23G
      with silicon oil or SF6 gas endotamponade. MATERIALS AND METHODS: This
      retrospective analysis comprised 18 patients (19 eyes). We applied EX-PRESS
      implants in 9 patients with neovascular glaucoma (NVG) and in 10 patients with
      non-NVG. All patients had earlier history of diabetes and vitrectomy 23G for
      diabetic complications. Intraocular pressure (IOP) was measured and compared
      before; 7 days; 1, 3, 6, and 12 months; and a year after the surgery. RESULTS:
      Application of the implant exhibited a lowering effect on IOP. After 1 month, 53%
      of patients had IOP values beyond 22 mmHg, while 86% after 1 year. CONCLUSION:
      The implant can be used to treat both NVG and non-NVG in diabetic patients
      following PPV.

PMID- 28435238
TI  - Automated versus manual oxygen titration in COPD exacerbation: machine or hands,
      this is the question.

PMID- 28435239
TI  - Pulmonary rehabilitation for COPD improves exercise time rather than exercise
      tolerance: effects and mechanisms.
AB  - BACKGROUND: COPD patients undergoing pulmonary rehabilitation (PR) show various
      responses. The purpose of this study was to investigate the possible mechanisms
      and predictors of the response to PR in COPD patients. METHODS: Thirty-six stable
      COPD patients underwent PR including a 4-week high-intensity exercise training
      program, and they were evaluated by cardiopulmonary exercise testing. All
      patients (mean age 69 years, severe and very severe COPD 94%) were classified
      into four groups by whether the exercise time (Tex) or the peak oxygen uptake
      [Formula: see text] increased after PR: two factors increased (both the Tex and
      the peak [Formula: see text] increased); two factors decreased; time only
      increased (the Tex increased, but the peak [Formula: see text] economized); and
      [Formula: see text] only increased (the Tex decreased, but the peak [Formula: see
      text] increased). Within all patients, the relationships between baseline
      variables and the post-to-pre-change ratio of the time-slope, Tex/(peak minus
      resting [Formula: see text]), were investigated. RESULTS: Compared with the two
      factors increased group (n=11), in the time only increased group (n=18), the mean
      differences from pre-PR at peak exercise in 1) minute ventilation [Formula: see
      text] (P=0.004), [Formula: see text] (P<0.0001), and carbon dioxide output
      [Formula: see text] (P<0.0001) were lower, 2) [Formula: see text]/ [Formula: see
      text] (P=0.034) and [Formula: see text]/ [Formula: see text] (P=0.006) were
      higher, and 3) the dead space/tidal volume ratio (VD/VT) and the dyspnea level
      were similar. After PR, there was no significant difference in the ratio of the
      observed peak heart rate (HR) to the predicted peak HR (220 - age [years])
      between the two groups. A significant negative correlation with the baseline time
      slope (r=-0.496, P=0.002) and a positive correlation with the baseline body mass
      index (BMI) (r=0.496, P=0.002) were obtained. CONCLUSIONS: PR in COPD patients
      improves Tex rather than exercise tolerance, economizing oxygen requirements,
      resulting in reduced ventilatory requirements without cardiac loads followed by
      reduced exertional dyspnea. In addition, the time-slope and BMI could be used to
      predict PR responses beforehand.

PMID- 28435240
TI  - Risk of pneumonia with budesonide-containing treatments in COPD: an individual
      patient-level pooled analysis of interventional studies.
AB  - BACKGROUND: Concerns have been raised that treatment of COPD with inhaled
      corticosteroids may increase pneumonia risk. Responding to a request from the
      European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled
      analysis of interventional studies compared pneumonia risk with inhaled
      budesonide-containing versus non-budesonide-containing treatments and the impact
      of other clinically relevant factors. METHODS: AstraZeneca-sponsored, parallel
      group, double-blind, randomized controlled trials meeting the following criteria
      were included: >8 weeks' duration; >=60 patients with COPD; inhaled budesonide
      treatment arm (budesonide/formoterol or budesonide); and non-budesonide
      containing comparator arm (formoterol or placebo). Primary and secondary outcomes
      were time to first pneumonia treatment-emergent serious adverse event (TESAE) and
      treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox
      regression models stratified by study. RESULTS: Eleven studies were identified;
      10,570 out of 10,574 randomized patients receiving >=1 dose of study treatment
      were included for safety analysis (budesonide-containing, n=5,750; non-budesonide
      containing, n=4,820). Maximum exposure to treatment was 48 months. The overall
      pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing
      treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83,
      1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36). The annual incidence of
      pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide
      containing treatments, respectively. Comparing budesonide/formoterol with non
      budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00
      (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively. For budesonide
      versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07
      for pneumonia TEAEs (95% CI: 0.83, 1.38). CONCLUSION: This pooled analysis found
      no statistically significant increase in overall risk for pneumonia TESAEs or
      TEAEs with budesonide-containing versus non-budesonide-containing treatments.
      However, a small increase in risk with budesonide-containing treatment cannot be
      ruled out; there is considerable heterogeneity in study designs and patient
      characteristics, particularly in the early budesonide studies, and each study
      contributes <40 pneumonia TESAEs.

PMID- 28435241
TI  - Magnitude of exercise capacity and quality of life improvement following repeat
      pulmonary rehabilitation in patients with COPD.
AB  - BACKGROUND: Maintenance and repeated pulmonary rehabilitation programs (PRPs) for
      patients with COPD have attempted to prolong PRP benefits beyond 12-24 months.
      However, there is limited evidence as to the magnitude of benefit or the ideal
      interval between repeating the program under "real-world" conditions in which
      patients are referred based on clinical necessity. Therefore, we reviewed the
      effects of repeating PRP in a physician-referred cohort of patients with COPD.
      METHODS: A total of 141 individuals with COPD completed PRP twice and 35
      completed PRP three times over a 12-year period. We used linear mixed-effects
      models to quantify the magnitude and change in 6-minute walk distance (6MWD), St
      George's Respiratory Questionnaire (SGRQ), and Hospital Anxiety and Depression
      Scale (HADS) for each PRP. One-way analysis of variance with Tukey's post hoc
      analysis compared the effects of different time intervals on 6MWD, SGRQ, and HADS
      between PRPs. RESULTS: Despite 39 mL/year average decrease in forced expiratory
      volume in 1 second, overall 6MWD improved following each PRP (PRP1=58 m,
      P<0.0001; PRP2=42 m, P<0.0001; PRP3=32 m, P<0.003). Mean SGRQ decreased after
      PRP1 (-7.0 units; P<0.001) and PRP2 (-4.9 units; P<0.0001) but not after PRP3 (
      3.2 units; P=0.10). HADS decreased after PRP1 (-1.9 units; P<0.0001) and PRP2 (
      1.7 units; P=0.0001) but not after PRP3 (-0.4 units; P=0.63). CONCLUSION: In
      physician-referred patients who underwent repeat PRP as clinically required,
      there were clear benefits in functional exercise capacity following each repeat
      PRP, which was not affected by the time interval between PRPs. Health-related
      quality of life and mood improved after the first two PRPs, but not after a
      third.

PMID- 28435242
TI  - Burden of asthma, dyspnea, and chronic cough in South Asia.
AB  - BACKGROUND: Asthma, dyspnea, and chronic cough are well-established risk factors
      of COPD and often associated with exacerbation of the disease, which is a leading
      cause of morbidity and mortality in South Asian countries. OBJECTIVE: The aims of
      this study were to, 1) measure the prevalence of asthma, dyspnea, and chronic
      cough, and 2) assess the relationship between these respiratory problems and self
      reported health status among South Asians. METHODS: Data for this research came
      from the World Health Survey (2002-2003) conducted by the World Health
      Organization. Subjects were 35,929 men and women, aged 18 years and older,
      selected from Bangladesh, India, Nepal, Pakistan, and Sri Lanka. Crude prevalence
      rates of asthma, dyspnea, and chronic cough were presented as percentages, and
      the results of their association with subjective health status were presented as
      odds ratios and corresponding 95% CIs. RESULTS: Prevalence of daily smoking was
      highest in Bangladesh (39.9%) and lowest in Sri Lanka (14.1%). Prevalence of
      asthma was highest in India (6.3%), while Nepal had the highest prevalence of
      dyspnea (11.3%) and chronic cough (15.3%). Overall prevalence of asthma and
      dyspnea was higher among women, while that of chronic cough was higher among men.
      Significant differences were observed in the prevalence rates of all the
      conditions among regular, occasional, and nonsmokers. A majority of the men and
      women who had asthma, dyspnea, and chronic cough had higher likelihood of
      reporting poor health status compared to those who did not have these diseases.
      CONCLUSION: Findings suggest that prevalence rates of asthma, dyspnea, and
      chronic cough were considerably high in all the countries and were significantly
      associated with poor subjective health. Being a high COPD-prone region, programs
      targeted to address these diseases could help reduce the burden of COPD and
      respiratory disease-related mortalities in South Asia.

PMID- 28435244
TI  - Accelerometer- versus questionnaire-based assessment of physical activity and
      their changes over time in patients with COPD.
AB  - BACKGROUND AND OBJECTIVE: Physical activity (PA) is an important outcome
      parameter in patients with COPD regarding hospitalizations and mortality. Both
      objective assessment by accelerometers and self-evaluation by questionnaires were
      used in studies investigating PA in COPD. Whether self-reported questionnaires
      can adequately reflect PA and its changes over time compared to objective
      assessments has not been thoroughly investigated in COPD. In this COPD cohort
      study, we evaluated whether PA measured by accelerometer and its annual changes
      can also be assessed by self-reported questionnaires. METHODS: In 178 COPD
      patients with at least two assessments of PA, the agreement between objectively
      measured and self-reported activity was analyzed by Bland-Altman plots. Daily PA
      was assessed by a triaxial activity monitor over 1 week and by the self-reported
      German PA questionnaire 50+. RESULTS: Comparison between the two methods of
      measurement revealed no convincing agreement with a mean difference and limits of
      agreement (+/-1.96 standard deviation [SD]) of time spent in at least moderate PA
      (>3 metabolic equivalent of task [MET]) of -77.6 (-340.3/185.2) min/day,
      indicating a self-reported overestimation of PA by the questionnaire. The mean
      difference and limits of agreement (+/-1.96SD) in the annual change of PA was 1.2
      min/day (-208.2/282.6 min/day), showing also a poor agreement on an individual
      level. CONCLUSION: Evaluation of objectively measured and self-reported PA and
      their annual changes revealed no agreement in patients with COPD. Therefore, the
      evaluated questionnaire seems not helpful for measurement of PA and its changes
      over time.

PMID- 28435243
TI  - Peripheral leukocyte microRNAs as novel biomarkers for COPD.
AB  - COPD is a multifactorial disease caused by environmental determinants as well as
      genetic risk factors. The prevalence and mortality of COPD continue to increase,
      and underdiagnosis of COPD remains a critical issue. Previous reports
      investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for
      the development of COPD; however, diagnostic and therapeutic markers for COPD
      have not yet been found. For this study, 20 representative COPD patients were
      separated into four groups based on increasing severity (A, B, C, and D) and
      compared to six healthy controls. Small RNA profiles of peripheral leukocytes
      were differentially expressed miRNAs (analyzed via next-generation sequencing)
      were validated via quantitative reverse transcriptase-polymerase chain reaction.
      Compared to healthy controls, 19 differentially expressed miRNAs were found in
      COPD patients. For all COPD groups, miR-3177-3p was downregulated, while 17
      miRNAs were upregulated. Furthermore, the results revealed 21 differentially
      expressed miRNAs, of which miR-183-5p was continually downregulated from A to B
      to D. Between respective bronchodilator reversibility positive and negative
      groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially
      expressed, while miR-100-5p was upregulated in the negative groups. In
      conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for
      the development of COPD. The severity of COPD was attenuated by miR-106b-5p, thus
      suggesting this miRNA as potential target for disease treatment.

PMID- 28435245
TI  - Long-term effects of beta-blocker use on lung function in Japanese patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Some recent studies have suggested that beta-blocker use in patients
      with chronic obstructive pulmonary disease (COPD) is associated with a reduction
      in the frequency of acute exacerbations. However, the long-term effects of beta
      blocker use on lung function of COPD patients have hardly been evaluated.
      PATIENTS AND METHODS: We retrospectively reviewed 31 Japanese COPD patients
      taking beta-blockers for >1 year and 72 patients not taking them. The association
      between beta-blocker use and the annual change in forced expiratory volume in 1
      second (FEV1) was assessed. RESULTS: At baseline, patient demographic
      characteristics were as follows: 97 males (mean age 67.0+/-8.2 years); 32 current
      smokers; and Global Initiative for Chronic Obstructive Lung disease (GOLD) stages
      I: n=26, II: n=52, III: n=19, and IV: n=6. Patients taking beta-blockers
      exhibited a significantly lower forced vital capacity (FVC), FEV1, and %FVC, and
      a more advanced GOLD stage. The mean duration of beta-blocker administration was
      2.8+/-1.7 years. There were no differences in the annual change in FEV1 between
      patients who did and did not use beta-blockers (-7.6+/-93.5 mL/year vs -4.7+/
      118.9 mL/year, P=0.671). After controlling for relevant confounders in
      multivariate analyses, it was found that beta-blocker use was not significantly
      associated with the annual decline in FEV1 (beta=-0.019; 95% confidence interval:
      -0.073 to 0.036; P=0.503). CONCLUSION: Long-term beta-blocker use in Japanese
      COPD patients might not affect the FEV1, one of the most important parameters of
      lung function in COPD patients.

PMID- 28435246
TI  - Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem
      cells.
AB  - Recent studies have shown that metal and metal oxide have a potential function in
      antitumor therapy. Our previous studies demonstrated that cuprous oxide
      nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in
      vitro but also inhibit the growth and metastasis of melanoma by targeting
      mitochondria with little hepatic and renal toxicities in mice. As a further
      study, our current research revealed that CONPs induced apoptosis of human
      melanoma stem cells (CD271+/high cells) in A375 and WM266-4 melanoma cell lines
      and could significantly suppress the expression of MITF, SOX10 and CD271 involved
      in the stemness maintenance and tumorigenesis of melanoma stem cells. CD271+/high
      cells could accumulate more CONPs than CD271-/low through clathrin-mediated
      endocytosis. In addition, lower dosage of CONPs exhibited good anti-melanoma
      effect by decreasing the cell viability, stemness and tumorigenesis of A375 and
      WM266-4 cells through reducing the expression of SOX10, MITF, CD271 and genes in
      MAPK pathway involved in tumor progression. Finally, CONPs obviously suppressed
      the growth of human melanoma in tumor-bearing nonobese diabetic-severe combined
      immunodeficiency (NOD-SCID) mice, accompanied with tumors structural necrosis and
      fibrosis remarkably and decreased expression of CD271, SOX10 and MITF. These
      results above proved the effectiveness of CONPs in inhibiting melanoma progress
      through multiple pathways, especially through targeting melanoma stem cells.

PMID- 28435247
TI  - Delivery of curcumin by directed self-assembled micelles enhances therapeutic
      treatment of non-small-cell lung cancer.
AB  - BACKGROUND: It has been widely reported that curcumin (CUR) exhibits anticancer
      activity and triggers the apoptosis of human A549 non-small-cell lung cancer
      (NSCLC) cells. However, its application is limited owing to its poor solubility
      and bioavailability. Therefore, there is an urgent need to develop a new CUR
      formulation with higher water solubility and better biocompatibility for clinical
      application in the future. MATERIALS AND METHODS: In this study, CUR-loaded
      methoxy polyethylene glycol-polylactide (CUR/mPEG-PLA) polymeric micelles were
      prepared by a thin-film hydration method. Their characteristics and antitumor
      effects were evaluated subsequently. RESULTS: The average size of CUR/mPEG-PLA
      micelles was 34.9+/-2.1 nm with its polydispersity index (PDI) in the range of
      0.067-0.168. The encapsulation efficiency and drug loading were 90.2%+/-0.78% and
      9.1%+/-0.07%, respectively. CUR was constantly released from the CUR/mPEG-PLA
      micelles, and its cellular uptake in A549 cells was significantly increased. It
      was also found that CUR/mPEG-PLA micelles inhibited A549 cell proliferation,
      increased the cell cytotoxicity, induced G2/M stage arrest and promoted cell
      apoptosis. Moreover, the CUR/mPEG-PLA micelles suppressed the migration and
      invasion of A549 cells more obviously than free CUR. Additionally, CUR/mPEG-PLA
      micelles inhibited human umbilical vein endothelial cells migration, invasion and
      corresponding tube formation, implying the antiangiogenesis ability. Its enhanced
      antitumor mechanism may be related to the reduced expression of vascular
      endothelial growth factor, matrix metalloproteinase (MMP)-2, MMP-9 and Bcl-2 as
      well as the increased expression of Bax. CONCLUSION: The mPEG-PLA copolymer
      micelles can serve as an efficient carrier for CUR. The CUR/mPEG-PLA micelles
      have promising clinical potential in treating NSCLC.

PMID- 28435248
TI  - Redox-sensitive Pluronic F127-tocopherol micelles: synthesis, characterization,
      and cytotoxicity evaluation.
AB  - Pluronic F127 (F127), an amphiphilic triblock copolymer, has been shown to have
      significant potential for drug delivery, as it is able to incorporate hydrophobic
      drugs and self-assemble into nanosize micelles. However, it suffers from
      dissociation upon dilution owing to the relatively high critical micelle
      concentration and lack of stimuli-responsive behavior. Here, we synthesized the
      alpha-tocopherol (TOC) modified F127 polymer (F127-SS-TOC) via a redox-sensitive
      disulfide bond between F127 and TOC, which formed stable micelles at relatively
      low critical micelle concentration and was sensitive to the intracellular redox
      environment. The particle size and zeta potential of the F127-SS-TOC micelles
      were 51.87+/-6.39 nm and -8.43+/-2.27 mV, respectively, and little changes in
      both particle size and zeta potential were observed within 7 days at room
      temperature. With 10 mM dithiothreitol stimulation, the F127-SS-TOC micelles
      rapidly dissociated followed by a significant change in size, which demonstrated
      a high reduction sensitivity of the micelles. In addition, the micelles showed a
      high hemocompatibility even at a high micelle concentration (1,000 MUg/mL). Low
      cytotoxicity of the F127-SS-TOC micelles at concentrations ranging from 12.5
      MUg/mL to 200 MUg/mL was also found on both Bel 7402 and L02 cells. Overall, our
      results demonstrated F127-SS-TOC micelles as a stable and safe aqueous
      formulation with a considerable potential for drug delivery.

PMID- 28435249
TI  - Detection of influenza viruses by coupling multiplex reverse-transcription loop
      mediated isothermal amplification with cascade invasive reaction using
      nanoparticles as a sensor.
AB  - Influenza virus infections represent a worldwide public health and economic
      problem due to the significant morbidity and mortality caused by seasonal
      epidemics and pandemics. Sensitive and convenient methodologies for detection of
      influenza viruses are essential for further disease control. Loop-mediated
      isothermal amplification (LAMP) is the most commonly used method of nucleic acid
      isothermal amplification. However, with regard to multiplex LAMP, differentiating
      the ladder-like LAMP products derived from multiple targets is still challenging
      today. The requirement of specialized instruments has further hindered the on
      site application of multiplex LAMP. We have developed an integrated assay
      coupling multiplex reverse transcription LAMP with cascade invasive reaction
      using nanoparticles (mRT-LAMP-CIRN) as a sensor for the detection of three
      subtypes of influenza viruses: A/H1N1pdm09, A/H3 and influenza B. The analytic
      sensitivities of the mRT-LAMP-CIRN assay were 101 copies of RNA for both
      A/H1N1pdm09 and A/H3, and 102 copies of RNA for influenza B. This assay
      demonstrated highly specific detection of target viruses and could differentiate
      them from other genetically or clinically related viruses. Clinical specimen
      analysis showed the mRT-LAMP-CIRN assay had an overall sensitivity and
      specificity of 98.3% and 100%, respectively. In summary, the mRT-LAMP-CIRN assay
      is highly sensitive and specific, and can be used as a cost-saving and instrument
      free method for the detection of influenza viruses, especially for on-site use.

PMID- 28435250
TI  - SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic
      biological effect with chemotherapy to combat colorectal cancer.
AB  - DNA nanostructures prepared by self-assembly possess good stability, high
      biocompatibility, and low immunogenicity as drug delivery vehicles. In this work,
      DNA tetrahedron (TD) was constructed and modified with SL2B aptamer (S) and folic
      acid (F). TD possessed a small diameter (~6 nm) and entered into the nucleus
      quickly. SL2B aptamer can inhibit cancer cell growth by disturbing vascular
      endothelial growth factor/Notch signaling pathways. To explore the effect of SL2B
      number on colorectal cancer inhibition, SL2B multimers (dimer, trimer, and
      tetramer) were constructed by functionalization of TD with different numbers of
      SL2B. One SL2B per TD was the most efficient anticancer strategy and showed
      significantly better anticancer efficacy than SL2B, probably due to the enhanced
      stability of SL2B by TD. Doxorubicin (DOX) is a potent anticancer agent that can
      intercalate into DNA double strands. Results showed that TD could facilitate DOX
      entrance into the nucleus and the intracellular delivery of DOX was further
      enhanced by functionalization of SL2B and F. DOX-intercalated TD modified with
      two F and two S (DOX@TD-2F2S) could cause sufficient HT-29 cell inhibition at a
      much lower DOX concentration. In sum, DOX@TD-2F2S exhibited a synergic anticancer
      biological effect with chemotherapy and can be a promising strategy for treating
      colorectal cancer.

PMID- 28435251
TI  - Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan
      scaffolds for bone regeneration in calvarial defects.
AB  - Hydroxyapatite (HAP; Ca10(PO4)6(OH)2) and whitlockite (WH; Ca18Mg2(HPO4)2(PO4)12)
      are widely utilized in bone repair because they are the main components of hard
      tissues such as bones and teeth. In this paper, we synthesized HAP and WH hollow
      microspheres by using creatine phosphate disodium salt as an organic phosphorus
      source in aqueous solution through microwave-assisted hydrothermal method. Then,
      we prepared HAP/chitosan and WH/chitosan composite membranes to evaluate their
      biocompatibility in vitro and prepared porous HAP/chitosan and WH/chitosan
      scaffolds by freeze drying to compare their effects on bone regeneration in
      calvarial defects in a rat model. The experimental results indicated that the
      WH/chitosan composite membrane had a better biocompatibility, enhancing
      proliferation and osteogenic differentiation ability of human mesenchymal stem
      cells than HAP/chitosan. Moreover, the porous WH/chitosan scaffold can
      significantly promote bone regeneration in calvarial defects, and thus it is more
      promising for applications in tissue engineering such as calvarial repair
      compared to porous HAP/chitosan scaffold.

PMID- 28435252
TI  - Polyphenol nanoformulations for cancer therapy: experimental evidence and
      clinical perspective.
AB  - Cancer is defined as the abnormal cell growth that can cause life-threatening
      malignancies with high financial costs for patients as well as the health care
      system. Natural polyphenols have long been used for the prevention and treatment
      of several disorders due to their antioxidant, anti-inflammatory, cytotoxic,
      antineoplastic, and immunomodulatory effects discussed in the literature; thus,
      these phytochemicals are potentially able to act as chemopreventive and
      chemotherapeutic agents in different types of cancer. One of the problems
      regarding the use of polyphenolic compounds is their low bioavailability.
      Different types of formulations have been designed for the improvement of
      bioavailability of these compounds, nanonization being one of the most notable
      approaches among them. This study aimed to review current data on the
      nanoformulations of natural polyphenols as chemopreventive and chemotherapeutic
      agents and to discuss their molecular anticancer mechanisms of action.
      Nanoformulations of natural polyphenols as bioactive agents, including
      resveratrol, curcumin, quercetin, epigallocatechin-3-gallate, chrysin, baicalein,
      luteolin, honokiol, silibinin, and coumarin derivatives, in a dose-dependent
      manner, result in better efficacy for the prevention and treatment of cancer. The
      impact of nanoformulation methods for these natural agents on tumor cells has
      gained wider attention due to improvement in targeted therapy and
      bioavailability, as well as enhancement of stability. Today, several
      nanoformulations are designed for delivery of polyphenolic compounds, including
      nanosuspensions, solid lipid nanoparticles, liposomes, gold nanoparticles, and
      polymeric nanoparticles, which have resulted in better antineoplastic activity,
      higher intracellular concentration of polyphenols, slow and sustained release of
      the drugs, and improvement of proapoptotic activity against tumor cells. To
      conclude, natural polyphenols demonstrate remarkable anticancer potential in
      pharmacotherapy; however, the obstacles in terms of their bioavailability in and
      toxicity to normal cells, as well as targeted drug delivery to malignant cells,
      can be overcome using nanoformulation-based technologies, which optimize the
      bioefficacy of these natural drugs.

PMID- 28435253
TI  - Antimicrobial photodynamic activity and cytocompatibility of Au25(Capt)18
      clusters photoexcited by blue LED light irradiation.
AB  - Antimicrobial photodynamic therapy (aPDT) has beneficial effects in dental
      treatment. We applied captopril-protected gold (Au25(Capt)18) clusters as a novel
      photosensitizer for aPDT. Photoexcited Au clusters under light irradiation
      generated singlet oxygen (1O2). Accordingly, the antimicrobial and cytotoxic
      effects of Au25(Capt)18 clusters under dental blue light-emitting diode (LED)
      irradiation were evaluated. 1O2 generation of Au25(Capt)18 clusters under blue
      LED irradiation (420-460 nm) was detected by a methotrexate (MTX) probe. The
      antimicrobial effects of photoexcited Au clusters (0, 5, 50, and 500 MUg/mL) on
      oral bacterial cells, such as Streptococcus mutans, Aggregatibacter
      actinomycetemcomitans, and Porphyromonas gingivalis, were assessed by
      morphological observations and bacterial growth experiments. Cytotoxicity testing
      of Au clusters and blue LED irradiation was then performed against NIH3T3 and
      MC3T3-E1 cells. In addition, the biological performance of Au clusters (500
      MUg/mL) was compared to an organic dye photosensitizer, methylene blue (MB; 10
      and 100 MUg/mL). We confirmed the 1O2 generation ability of Au25(Capt)18 clusters
      through the fluorescence spectra of oxidized MTX. Successful application of
      photoexcited Au clusters to aPDT was demonstrated by dose-dependent decreases in
      the turbidity of oral bacterial cells. Morphological observation revealed that
      application of Au clusters stimulated destruction of bacterial cell walls and
      inhibited biofilm formation. Aggregation of Au clusters around bacterial cells
      was fluorescently observed. However, photoexcited Au clusters did not negatively
      affect the adhesion, spreading, and proliferation of mammalian cells,
      particularly at lower doses. In addition, application of Au clusters demonstrated
      significantly better cytocompatibility compared to MB. We found that a
      combination of Au25(Capt)18 clusters and blue LED irradiation exhibited good
      antimicrobial effects through 1O2 generation and biosafe characteristics, which
      is desirable for aPDT in dentistry.

PMID- 28435254
TI  - Daphnia magna and Xenopus laevis as in vivo models to probe toxicity and uptake
      of quantum dots functionalized with gH625.
AB  - The use of quantum dots (QDs) for nanomedicine is hampered by their potential
      toxicologic effects and difficulties with delivery into the cell interior. We
      accomplished an in vivo study exploiting Daphnia magna and Xenopus laevis to
      evaluate both toxicity and uptake of QDs coated with the membranotropic peptide
      gH625 derived from the glycoprotein H of herpes simplex virus and widely used for
      drug delivery studies. We evaluated and compared the effects of QDs and gH625-QDs
      on the survival, uptake, induction of several responsive pathways and
      genotoxicity in D. magna, and we found that QDs coating plays a key role.
      Moreover, studies on X. laevis embryos allowed to better understand their
      cell/tissue localization and delivery efficacy. X. laevis embryos raised in Frog
      Embryo Teratogenesis Assay-Xenopus containing QDs or gH625-QDs showed that both
      nanoparticles localized in the gills, lung and intestine, but they showed
      different distributions, indicating that the uptake of gH625-QDs was enhanced;
      the functionalized QDs had a significantly lower toxic effect on embryos'
      survival and phenotypes. We observed that D. magna and X. laevis are useful in
      vivo models for toxicity and drug delivery studies.

PMID- 28435255
TI  - Recent developments in the nanostructured materials functionalized with ruthenium
      complexes for targeted drug delivery to tumors.
AB  - In recent years, the field of metal-based drugs has been dominated by other
      existing precious metal drugs, and many researchers have focused their attention
      on the synthesis of various ruthenium (Ru) complexes due to their potential
      medical and pharmaceutical applications. The beneficial properties of Ru, which
      make it a highly promising therapeutic agent, include its variable oxidation
      states, low toxicity, high selectivity for diseased cells, ligand exchange
      properties, and the ability to mimic iron binding to biomolecules. In addition,
      Ru complexes have favorable adsorption properties, along with excellent
      photochemical and photophysical properties, which make them promising tools for
      photodynamic therapy. At present, nanostructured materials functionalized with Ru
      complexes have become an efficient way to administer Ru-based anticancer drugs
      for cancer treatment. In this review, the recent developments in the
      nanostructured materials functionalized with Ru complexes for targeted drug
      delivery to tumors are discussed. In addition, information on "traditional" (ie,
      non-nanostructured) Ru-based cancer therapies is included in a precise manner.

PMID- 28435256
TI  - Doxorubicin-loaded cell-derived nanovesicles: an alternative targeted approach
      for anti-tumor therapy.
AB  - Cell-derived nanovesicles (CDNs) are an emerging class of biological drug
      delivery systems (DDS) that retain the characteristics of the cells they were
      derived from, without the need for further surface functionalization. CDNs are
      also biocompatible, being derived from natural sources and also take advantage of
      the enhanced permeability and retention effect due to their nanodimensions.
      Furthermore, CDNs derived from monocytes were shown to have an in vivo targeting
      effect, accumulating at the tumor site in a previous study conducted in a mouse
      tumor model. Here, we report a systematic approach pertaining to various loading
      methods of the chemotherapeutic drug doxorubicin into our CDNs and examine the
      differential cellular uptake of drug-loaded CDNs in cancerous (HeLa) and healthy
      (HEK293) cell lines. Lastly, we proved that the addition of doxorubicin-loaded
      CDNs to the HeLa and HEK293 co-cultures showed a clear discrimination toward
      cancer cells at the cellular level. Our results further reinforce the intriguing
      potential of CDNs as an alternative targeted strategy for anticancer therapy.

PMID- 28435257
TI  - Effects of arginine-glycine-aspartic acid peptide-conjugated quantum dots-induced
      photodynamic therapy on pancreatic carcinoma in vivo.
AB  - Quantum dots (QDs) conjugated with integrin antagonist arginine-glycine-aspartic
      acid (RGD) peptides (QDs-RGD) are novel nanomaterials with a unique optical
      property: a high molar extinction coefficient. Previously, we have shown that QDs
      RGD demonstrate a photodynamic therapy (PDT) effect as new photosensitizers for
      the pancreatic cancer cell line SW1990 in vitro. Here, we investigate the
      application of QDs-RGD in mice bearing pancreatic tumors using PDT. To ensure
      that more photosensitizers accumulated in tumors, QDs-RGD were injected
      intratumorally. After selection of an adequate dosage for injection from analyses
      of biodistribution images captured by an IVIS system, PDT was initiated. Three
      groups were created according to different PDT procedures. In group 1, mice were
      injected with QDs-RGD intratumorally, and an optical fiber connected to a laser
      light was inserted directly into the tumor. Irradiation was sustained for 20 min
      with a laser light (630 nm) at 100 mW/cm2. In group 2, the laser optical fiber
      was placed around, and not inserted into, tumors. In group 3, PDT was conducted
      as in group 1 but without injection of QDs-RGD. After 28 days of observation,
      tumors on the back of mice in group 1 grew slowly (V/V0 =3.24+/-0.70) compared
      with the control groups, whose tumors grew quickly, and the mean V/V0 reached
      6.08+/-0.50 (group 2) and 7.25+/-0.82 (group 3). Histology of tumor tissues
      showed more necrotic tissues, more inflammatory cells, and less vascular tissue
      in the PDT group than those in the control groups. These results suggest that QDs
      RGD-mediated PDT, with illumination using an optical fiber inserted directly into
      the tumor, can inhibit the growth of SW1990 tumors with high efficiency in nude
      mice.

PMID- 28435258
TI  - Quantum dots modulate intracellular Ca2+ level in lung epithelial cells.
AB  - While adverse effects of nanoparticles on lung health have previously been
      proposed, few studies have addressed the direct effects of nanoparticle exposure
      on the airway epithelium. In this work, we examine the response of the pulmonary
      airway to nanoparticles by measuring intracellular Ca2+ concentration ([Ca2+]i)
      in the Calu-3 epithelial layer stimulated by 3-mercaptopropionic-acid (3MPA)
      coated CdSe-CdS/ZnS core-multishell quantum dots (QDs). Simultaneous transient
      transepithelial electrical resistance (TEER) decrease and global [Ca2+]i increase
      in Calu-3 epithelial layer, accompanied by cell displacements, contraction, and
      expansion, were observed under QD deposition. This suggests that a QD-induced
      global [Ca2+]i increase in the Calu-3 epithelial layer caused the transient TEER
      decrease. The [Ca2+]i increase was marked and rapid in the apical region, while
      [Ca2+]i decreased in the basolateral region of the epithelial layer. TEER
      transient response and extracellular Ca2+ entry induced by QD deposition were
      completely inhibited in cells treated with stretched-activated (SA) inhibitor
      GdCl3 and store-operated calcium entry (SOCE) inhibitor BTP2 and in cells
      immersed in Ca2+-free medium. The voltage-gated calcium channel (VGCC) inhibitor
      nifedipine decreased, stabilized, and suppressed the TEER response, but did not
      affect the [Ca2+]i increase, due to QD deposition. This demonstrates that the
      Ca2+ influx activated by QDs' mechanical stretch occurs through activation of
      both SA and SOCE channels. QD-induced [Ca2+]i increase occurred in the Calu-3
      epithelial layer after culturing for 15 days, while significant TEER drop only
      occurred after 23 days. This work provides a new perspective from which to study
      direct interactions between airway epithelium and nanoparticles and may help to
      reveal the pathologies of pulmonary disease.

PMID- 28435259
TI  - Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse
      free treatment of T24 bladder tumors.
AB  - Heat-based approaches have been considered as promising tools due to their
      ability to directly eradicate tumor cells and/or increase the sensitivity of
      tumors to radiation- or chemotherapy. In particular, the heating of magnetic
      nanoparticles (MNPs) via an alternating magnetic field can provide a handy
      alternative for a localized tumor treatment. To amplify the efficacy of
      magnetically induced thermal treatments, we elucidated the superior tumor
      destructive effect of methotrexate-coupled MNPs (MTX/MNPs) in combination with
      magnetic heating (nanochemothermia) over the thermal treatment alone. Our studies
      in a murine bladder xenograft model revealed the enormous potential of
      nanochemothermia for a localized and relapse-free destruction of tumors which was
      superior to the thermal treatment alone. Nanochemothermia remarkably fostered the
      reduction of tumor volume. It impaired proapoptotic signaling (eg, p-p53), cell
      survival (eg, p-ERK1/2), and cell cycle (cyclins) pathways. Additionally, heat
      shock proteins (eg, HSP70) were remarkably affected. Moreover, nanochemothermia
      impaired the induction of angiogenic signaling by decreasing, for example, the
      levels of VEGF-R1 and MMP9, although an increasing tumor hypoxia was indicated by
      elevated Hif-1alpha levels. In contrast, tumor cells were able to recover after
      the thermal treatments alone. In conclusion, nanochemothermia on the basis of
      MTX/MNPs was superior to the thermal treatment due to a modification of cellular
      pathways, particularly those associated with the cellular survival and tumor
      vasculature. This allowed very efficient and relapse-free destruction of tumors.

PMID- 28435260
TI  - Development of gold nanoparticles coated with silica containing the antibiofilm
      drug cinnamaldehyde and their effects on pathogenic bacteria.
AB  - Emerging resistance to antibiotics is a mounting worldwide health concern and
      increases the need for nonantibiotic strategies to combat infectious diseases
      caused by bacterial pathogens. In this study, the authors used the antibiofilm
      activity of the naturally occurring antimicrobial cinnamaldehyde (CNMA)
      conjugated to the surface of gold nanoparticles (GNPs) to deliver CNMA
      efficiently and eradicate biofilms of Gram-negative organisms (enterohemorrhagic
      Escherichia coli O157:H7, and Pseudomonas aeruginosa), Gram positive (methicillin
      sensitive Staphylococcus aureus organisms, and methicillin-resistant
      Staphylococcus aureus) bacteria. CNMA-GNPs containing 0.005% (v/v) of CNMA were
      found to inhibit biofilm formation efficiently. The distributions of
      nanoparticles in biofilm cells and their biofilm disruption activities, including
      distorted cell morphology, were determined by transmission electron microscopy.
      In addition to their antibiofilm activities, CNMA-GNPs attenuated S. aureus
      virulence and protected Caenorhabditis elegans (C. elegans) worms. Here, the
      authors report the antibiofilm effects of CNMA-GNPs and suggest that they could
      be used to treat pathogenic bacterial infections in vivo.

PMID- 28435261
TI  - pH-sensitive Au-BSA-DOX-FA nanocomposites for combined CT imaging and targeted
      drug delivery.
AB  - Albumin-based nanoparticles (NPs) as a drug delivery system have attracted much
      attention owing to their nontoxicity, non-immunogenicity, great stability and
      ability to bind to many therapeutic drugs. Herein, bovine serum albumin (BSA) was
      utilized as a template to prepare Au-BSA core/shell NPs. The outer layer BSA was
      subsequently conjugated with cis-aconityl doxorubicin (DOX) and folic acid (FA)
      to create Au-BSA-DOX-FA nanocomposites. A list of characterizations was
      undertaken to identify the successful conjugation of drug molecules and targeted
      agents. In vitro cytotoxicity using a cell counting kit-8 (CCK-8) assay indicated
      that Au-BSA NPs did not display obvious cytotoxicity to MGC-803 and GES-1 cells
      in the concentration range of 0-100 MUg/mL, which can therefore be used as a safe
      drug delivery carrier. Furthermore, compared with free DOX, Au-BSA-DOX-FA
      nanocomposites exhibited a pH-sensitive drug release ability and superior
      antitumor activity in a drug concentration-dependent manner. In vivo computed
      tomography (CT) imaging experiments showed that Au-BSA-DOX-FA nanocomposites
      could be used as an efficient and durable CT contrast agent for targeted CT
      imaging of the folate receptor (FR) overexpressed in cancer tissues. In vivo
      antitumor experiments demonstrated that Au-BSA-DOX-FA nanocomposites have
      selective antitumor activity effects on FR-overexpressing tumors and no adverse
      effects on normal tissues and organs. In conclusion, the Au-BSA-DOX-FA
      nanocomposite exhibits selective targeting activity, X-ray attenuation activity
      and pH-sensitive drug release activity. Therefore, it can enhance CT imaging and
      improve the targeting therapeutic efficacy of FR-overexpressing gastric cancers.
      Our findings suggest that Au-BSA-DOX-FA nanocomposite is a novel drug delivery
      carrier and a promising candidate for cancer theranostic applications.

PMID- 28435262
TI  - Linseed hydrogel-mediated green synthesis of silver nanoparticles for
      antimicrobial and wound-dressing applications.
AB  - Polysaccharides are being extensively employed for the synthesis of silver
      nanoparticles (Ag NPs) having diverse morphology and applications. Herein, we
      present a novel and green synthesis of Ag NPs without using any physical reaction
      conditions. Linseed hydrogel (LSH) was used as a template to reduce Ag+ to Ag0.
      AgNO3 (10, 20, and 30 mmol) solutions were mixed with LSH suspension in deionized
      water and exposed to diffused sunlight. Reaction was monitored by noting the
      change in the color of reaction mixture up to 10 h. Ag NPs showed characteristic
      ultraviolet-visible (UV/Vis) absorptions from 410 to 437 nm in the case of
      sunlight and 397-410 nm in the case of temperature study. Transmission electron
      microscopy images revealed the formation of spherical Ag NPs in the range of 10
      35 nm. Face-centered cubic array of Ag NPs was confirmed by characteristic
      diffraction peaks in powder X-ray diffraction spectrum. Ag NPs were stored in LSH
      thin films, and UV/Vis spectra recorded after 6 months indicated that Ag NPs
      retained their texture over the storage period. Significant antimicrobial
      activity was observed when microbial cultures (bacteria and fungi) were exposed
      to the synthesized Ag NPs. Wound-healing studies revealed that Ag NP-impregnated
      LSH thin films could have potential applications as an antimicrobial dressing in
      wound management procedures.

PMID- 28435263
TI  - Neuroprotection against apoptosis of SK-N-MC cells using RMP-7- and lactoferrin
      grafted liposomes carrying quercetin.
AB  - A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with
      RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the
      blood-brain barrier (BBB) and rescue degenerated neurons, acting as an
      Alzheimer's disease (AD) pharmacotherapy. This colloidal formulation of QU
      encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse
      human brain microvascular endothelial cells (HBMECs) regulated by human
      astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic beta
      amyloid (Abeta) fibrils. We found that surface RMP-7 and Lf enhanced the ability
      of QU to cross the BBB without inducing strong toxicity and damaging the tight
      junction. In addition, RMP-7-Lf-QU-LS significantly reduced Abeta-induced
      neurotoxicity and improved the viability of SK-N-MC cells. Compared with free QU,
      RMP-7-Lf-QU-LS could also significantly inhibit the expression of phosphorylated
      c-Jun N terminal kinase, phosphorylated p38, and phosphorylated tau protein at
      serine 202 by SK-N-MC cells, indicating an important role of RMP-7, Lf, and LS in
      protecting neurons against apoptosis. RMP-7-Lf-QU-LS is a promising carrier
      targeting the BBB to prevent Abeta-insulted neurodegeneration and may have
      potential in managing AD in future clinical applications.

PMID- 28435264
TI  - Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by
      lipid emulsions for improved treatment of cancer.
AB  - Combinational nanomedicine is becoming a topic of much interest in cancer
      therapy, although its translation into the clinic remains extremely challenging.
      One of the main obstacles lies in the difficulty to efficiently co-deliver
      immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study
      was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible
      hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co
      delivery abilities between co-loaded LEs and mixture formulation. Multiple
      oxaliplatin/irinotecan drug-phospholipid complexes (DPCs) were formulated. Co
      loaded LEs were prepared using DPC technique to efficiently encapsulate both
      drugs. Co-loaded LEs exhibited uniform particle size distribution, desired
      stability and synchronous release profiles in both drugs. Co-loaded LEs
      demonstrated superior anti-tumor activity compared with the simple solution
      mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers
      could co-deliver both drugs into the same cells more efficiently and exhibited
      the optimized synergistic effect. These results indicate that co-loaded LEs could
      be a desired formulation for enhanced cancer therapy with potential application
      prospects. The comparison between co-loaded LEs and mixture formulation is
      significant for pharmaceutical designs aimed at co-delivery of multiple drugs.

PMID- 28435265
TI  - Toxicity studies of six types of carbon nanoparticles in a chicken-embryo model.
AB  - In the present study, the toxicity of six different types of carbon nanoparticles
      (CNPs) was investigated using a chicken-embryo model. Fertilized chicken eggs
      were divided into the following treatment groups: placebo, diamond NPs, graphite
      NPs, pristine graphene, small graphene oxide, large graphene oxide, and reduced
      graphene oxide. Experimental solutions at a concentration of 500 MUg/mL were
      administrated into the egg albumin. Gross pathology and the rate of survival were
      examined after 5, 10, 15, and 20 days of incubation. After 20 days of incubation,
      blood samples were collected and the weight of the body and organs measured. The
      relative ratio of embryo survival decreased after treatment all treatments except
      diamond NPs. There was no correlation between the rate of survival and the zeta
      potential or the surface charge of the CNPs in solution. Body and organ weight,
      red blood-cell morphology, blood serum biochemical parameters, and oxidative
      damage in the liver did not differ among the groups. These results indicate that
      CNPs can remain in blood circulation without any major side effects, suggesting
      their potential applicability as vehicles for drug delivery or active compounds
      per se. However, there is a need for further investigation of their properties,
      which vary depending on production methods and surface functionalization.

PMID- 28435266
TI  - EGFR-targeted delivery of DOX-loaded Fe3O4@ polydopamine multifunctional
      nanocomposites for MRI and antitumor chemo-photothermal therapy.
AB  - Multifunctional nanocomposites that have multiple therapeutic functions together
      with real-time imaging capabilities have attracted intensive concerns in the
      diagnosis and treatment of cancer. This study developed epidermal growth factor
      receptor (EGFR) antibody-directed polydopamine-coated Fe3O4 nanoparticles
      (Fe3O4@PDA NPs) for magnetic resonance imaging and antitumor chemo-photothermal
      therapy. The synthesized Fe3O4@PDA-PEG-EGFR-DOX NPs revealed high storage
      capacity for doxorubicin (DOX) and high photothermal conversion efficiency. The
      cell viability assay of Fe3O4@PDA-PEG-EGFR NPs indicated that Fe3O4@ PDA-PEG-EGFR
      NPs had no cell cytotoxicity. However, Fe3O4@PDA-PEG-EGFR-DOX NPs could
      significantly decrease cell viability (~5% of remaining cell viability) because
      of both photothermal ablation and near-infrared light-triggered DOX release.
      Meanwhile, the EGFR-targeted Fe3O4@PDA-PEG-EGFR-DOX NPs significantly inhibited
      the growth of tumors, showing a prominent in vivo synergistic antitumor effect.
      This study demonstrated the potential of using Fe3O4@PDA NPs for combined cancer
      chemo-photothermal therapy with increased efficacy.

PMID- 28435267
TI  - The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after
      intratracheal instillation in mice.
AB  - Cerium oxide nanoparticles (CeO2 NPs), used as a diesel fuel catalyst, can be
      emitted into the ambient air, resulting in exposure to humans by inhalation.
      Recent studies have reported the development of lung toxicity after pulmonary
      exposure to CeO2 NPs. However, little is known about the possible thrombotic
      effects of these NPs. The present study investigated the acute (24 hours) effect
      of intratracheal (IT) instillation of either CeO2 NPs (0.1 or 0.5 mg/kg) or
      saline (control) on pulmonary and systemic inflammation and oxidative stress and
      thrombosis in mice. CeO2 NPs induced a significant increase of neutrophils into
      the bronchoalveolar lavage (BAL) fluid with an elevation of tumor necrosis factor
      alpha (TNFalpha) and a decrease in the activity of the antioxidant catalase. Lung
      sections of mice exposed to CeO2 NPs showed a dose-dependent infiltration of
      inflammatory cells consisting of macrophages and neutrophils. Similarly, the
      plasma levels of C-reactive protein and TNFalpha were significantly increased,
      whereas the activities of catalase and total antioxidant were significantly
      decreased. Interestingly, CeO2 NPs significantly and dose dependently induced a
      shortening of the thrombotic occlusion time in pial arterioles and venules.
      Moreover, the plasma concentrations of fibrinogen and plasminogen activator
      inhibitor-1 were significantly elevated by CeO2 NPs. The direct addition of CeO2
      NPs (1, 5, or 25 MUg/mL) to mouse whole blood, collected from the inferior vena
      cava, in vitro neither caused significant platelet aggregation nor affected
      prothrombin time or partial thromboplastin time, suggesting that the thrombotic
      events observed in vivo may have resulted from systemic inflammation and/or
      oxidative stress induced by CeO2 NPs. This study concludes that acute pulmonary
      exposure to CeO2 NPs induces pulmonary and systemic inflammation and oxidative
      stress and promotes thrombosis in vivo.

PMID- 28435268
TI  - Biocompatible nanoemulsions based on hemp oil and less surfactants for oral
      delivery of baicalein with enhanced bioavailability.
AB  - Baicalein (BCL) possesses high pharmacological activities but low solubility and
      stability in the intestinal tract. This study aimed to probe the potential of
      nanoemulsions (NEs) consisting of hemp oil and less surfactants in ameliorating
      the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs) were prepared by high
      pressure homogenization technique to reduce the amount of surfactants. BCL-NEs
      were characterized by particle size, entrapment efficiency (EE), in vitro drug
      release, and morphology. Bioavailability was studied in Sprague-Dawley rats
      following oral administration of BCL suspensions, BCL conventional emulsions, and
      BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL
      NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and
      242.1% relative to the suspensions and conventional emulsions, respectively. BCL
      NEs exhibited excellent intestinal permeability and transcellular transport
      ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for
      oral purpose. Our findings suggest that such novel NEs and preparative process
      provide a promising alternative to current formulation technologies and suitable
      for oral delivery of drugs with bioavailability issues.

PMID- 28435269
TI  - Efficacy of silk fibroin-nano silver against Staphylococcus aureus biofilms in a
      rabbit model of sinusitis.
AB  - BACKGROUND: Staphylococcus aureus biofilms contribute significantly to the
      recalcitrant nature of chronic rhinosinusitis. In previous studies, it has been
      shown that silk fibroin-nano silver solution can eliminate S. aureus biofilms in
      vitro, which suggests a potential role of this novel agent in the treatment of
      biofilm-associated diseases, such as sinusitis. OBJECTIVE: The aim of this study
      was to investigate the efficacy of silk fibroin-nano silver solution as a topical
      anti-biofilm agent in a rabbit model of sinusitis. METHODS: Biofilm-associated
      sinusitis models were established in 24 New Zealand White rabbits by gelatin
      sponge placement and S. aureus inoculation through a hole drilled into the
      anterolateral wall of the right maxillary sinus. After 4 weeks, indwelling
      catheters were placed into the maxillary sinus. Different concentrations of silk
      fibroin-nano silver solution or normal saline were irrigated slowly into the
      maxillary sinus via the indwelling catheters. After 7 days of irrigation, the
      rabbits were sacrificed. The sinus mucosa was harvested and examined for biofilm
      biomass as well as morphological integrity of the epithelium by scanning electron
      microscopy. RESULTS: Silk fibroin-nano silver solution was found to be most
      effective in reducing the biomass of the S. aureus biofilms at a concentration of
      384 mg/L, followed by the concentration of 153.6 mg/L, when compared with saline.
      After treatment with 384 mg/L silk fibroin-nano silver solution, the biofilms
      were completely eliminated and the injured epithelium was almost restored with
      regenerated cilia on the surface. CONCLUSION: Silk fibroin-nano silver solution
      was found to be an effective topical agent against S. aureus biofilms in the
      rabbit model of sinusitis, and its effect was concentration-dependent.

PMID- 28435270
TI  - Relationship between hypnosis and personality trait in participants with high or
      low hypnotic susceptibility.
AB  - BACKGROUND: The relationship between normal personality and hypnotic
      susceptibility is important for understanding mental processing and mental
      disorders, but it is less consistent in normal people or in patients with a
      psychiatric disorder. We have hypothesized that the correlation exists but varies
      in individuals with different levels of hypnotizability. PARTICIPANTS AND
      METHODS: We invited 72 individuals with high (HIGH group) and 47 individuals with
      low (LOW group) hypnotic susceptibilities to undertake tests of NEO-PI-R and the
      Stanford Hypnotic Susceptibility Scale, Form C (SHSSC). RESULTS: The HIGH group
      scored significantly higher than the LOW group did on openness to experience and
      its facet openness to feelings. In the LOW group, SHSSC total was positively
      predicted by openness to ideas; age regression was positively predicted by
      openness to experience and negatively predicted by extraversion; anosmia to
      ammonia was negatively predicted by agreeableness; and negative visual
      hallucination was positively predicted by openness to experience. In the HIGH
      group, hallucinated voice was positively predicted by openness to experience and
      negatively predicted by agreeableness, and posthypnotic amnesia was positively
      predicted by extraversion and negatively predicted by openness to experience.
      CONCLUSION: The associations between normal personality traits and hypnotic
      susceptibility items were weak and different in the two groups, which imply that
      managing mental or somatoform disorders might be through adjusting
      hypnotizability and mobilizing personality functions.

PMID- 28435271
TI  - Recombinant human brain-derived neurotrophic factor prevents neuronal apoptosis
      in a novel in vitro model of subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) is a hemorrhagic stroke with high mortality and
      morbidity. An animal model for SAH was established by directly injecting a
      hemolysate into the subarachnoid space of rats or mice. However, the in vitro
      applications of the hemolysate SAH model have not been reported, and the
      mechanisms remain unclear. In this study, we established an in vitro SAH model by
      treating cortical pyramidal neurons with hemolysate. Using this model, we
      assessed the effects of recombinant human brain-derived neurotrophic factor
      (rhBDNF) on hemolysate-induced cell death and related mechanisms. Cortical
      neurons were treated with 10 ng/mL or 100 ng/mL rhBDNF prior to application of
      hemolysate. Hemolysate treatment markedly increased cell loss, triggered
      apoptosis, and promoted the expression of caspase-8, caspase-9, and cleaved
      caspase-3. rhBDNF significantly inhibited hemolysate-induced cell loss, neuronal
      apoptosis, and expression of caspase-8, caspase-9, and cleaved caspase-3. Our
      data revealed a previously unrecognized protective activity of rhBDNF against
      hemolysate-induced cell death, potentially via regulation of caspase-9-, caspase
      8-, and cleaved caspase-3-related apoptosis. This study implicates that
      hemolysate-induced cortical neuron death represents an important in vitro model
      of SAH.

PMID- 28435272
TI  - Quetiapine monotherapy versus placebo in the treatment of children and
      adolescents with bipolar depression: a systematic review and meta-analysis.
AB  - BACKGROUND: Some studies have indicated the efficacy of quetiapine in the
      treatment of bipolar depression in adult patients. However, its efficacy has been
      not shown in child and adolescent patients. OBJECTIVE: This systematic review
      purposefully determined the efficacy and acceptability of quetiapine in the
      treatment of children and adolescents with bipolar depression. DATA SOURCES: A
      database search of EMBASE, PubMed, CINAHL, and Cochrane Controlled Trials
      Register was carried out in March 2016. All randomized controlled trials (RCTs)
      of bipolar depression in children and adolescents were considered for inclusion
      in this review. STUDY ELIGIBILITY CRITERIA PARTICIPANTS AND INTERVENTIONS: RCTs
      of quetiapine in the treatment of child and adolescent patients with bipolar
      depression with end point outcomes were included in this study. Languages were
      not limited. STUDY APPRAISAL AND SYNTHESIS METHODS: The full-text versions of
      relevant clinical studies were thoroughly examined and extracted. The primary
      efficacy of outcome was measured by using the pooled mean-changed scores of the
      rating scales for bipolar depression. However, the response and remission rates
      were also measured. RESULTS: A total of 251 randomized patients in the three RCTs
      of quetiapine versus placebo in the treatment of bipolar depression for children
      and adolescents were eligible in this review. The pooled mean-changed score of
      the quetiapine-treated group was not greater than that of the placebo-treated
      group. Similarly, the pooled response and remission rates were not different
      between the two groups. The pooled overall discontinuation rate and the
      discontinuation rate due to adverse events were not different between the two
      groups. LIMITATIONS: Limited studies were eligible in this review. CONCLUSION:
      According to the findings in this review, quetiapine may not be efficacious in
      the treatment of bipolar depression in children and adolescents. Its
      acceptability, however, was comparable to a placebo. Therefore, the use of
      quetiapine in children and adolescents with bipolar depression is not
      recommended. Further well-defined clinical studies should be performed to confirm
      these outcomes.

PMID- 28435273
TI  - An innovative nonpharmacological intervention combined with intravenous patient
      controlled analgesia increased patient global improvement in pain and
      satisfaction after major surgery.
AB  - PURPOSE: This study aimed to evaluate whether a nonpharmacological approach
      through implementation of a communication improvement program (named CICARE for
      Connect, Introduce, Communicate, Ask, Respond and Exit) into standard operating
      procedure (SOP) in acute pain service (APS) improved satisfaction in patients
      receiving intravenous patient-controlled analgesia (IV-PCA). PATIENTS AND
      METHODS: This was a nonrandomized before-after study. Adult patients (aged
      between 20 and 80 years) who received IV-PCA after major surgery were included.
      Implementing CICARE into SOP was conducted in APS. Anonymous questionnaires were
      used to measure outcomes in this prospective two-part survey. The first part
      completed by APS nurses contained patients' characteristics, morphine dosage,
      delivery/demand ratios, IV-PCA side effects and pain at rest measured with an 11
      point numeric rating scale (NRS, 0-10). A score of NRS >=4 was defined as
      inadequately treated pain. The ten-question second part was completed by patients
      voluntarily after IV-PCA was discontinued. Each question was assessed with a 5
      point Likert scale (1: extremely poor; 5: excellent). Patients were separated
      into "before" and "after" CICARE groups. Primary outcomes were patient global
      impression of improvement in pain (PGI-Improvement) and patient satisfaction.
      Secondary outcomes included quality of communication skills, instrument
      proficiency and accessibility/availability of IV-PCA. RESULTS: The response rate
      was 55.3%, with 187 usable questionnaires. CICARE effectively improved patient
      global impression of improvement in pain, patient satisfaction, communication
      skills and accessibility/availability of IV-PCA. No significant differences were
      noted in instrument proficiency, morphine dosage, delivery/demand ratios, rates
      of inadequately treated pain at rest and side effects of IV-PCA between groups.
      Paradoxical findings were noted between the rates of inadequately treated
      pain/side effects and PGI-Improvement in pain/patient satisfaction, which were
      affected by psychological factors. CONCLUSION: Nonpharmacological interventions
      carried out by implementing CICARE into SOP for APS effectively improved patient
      satisfaction and postoperative pain management quality, but this did not affect
      actual pain.

PMID- 28435274
TI  - Hashimoto encephalopathy with high plasma monoamine metabolite levels: a case
      report.
AB  - Hashimoto encephalopathy (HE) is believed to be an immune-mediated disorder
      associated with Hashimoto's thyroiditis. It was suggested that neuropsychiatric
      symptoms, the presence of antithyroid antibody, and good response to steroids
      were important for the diagnosis of HE. It has been reported that homovanillic
      acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), which are monoamine
      metabolites of dopamine and noradrenaline, respectively, are the possible
      biomarkers of neuropsychiatric diseases. We report a case of Hashimoto
      encephalopathy, in which we longitudinally measured the plasma levels of
      monoamine metabolites. A 52-year-old woman developed acute psychosis, and was
      admitted to the psychiatric ward of our hospital due to psychotic state, 6 days
      after a traffic accident. An extensive evaluation showed no remarkable findings,
      except an increase in antithyroglobulin antibodies. Plasma levels of HVA and MHPG
      were extremely high at 66.5 and 41.8 ng/mL, respectively. On day 16, 50 mg/day
      oral prednisolone was administered, which improved her psychotic symptoms. Plasma
      levels of HVA and MHPG decreased to 7.2 and 9.9 ng/mL, respectively, on day 19.
      After the temporary worsening of psychosis and increase in plasma levels of HVA
      and MHPG, the dosage of prednisolone was tapered and low-dose risperidone was
      started. Her psychiatric symptoms gradually improved and plasma monoamine
      metabolite levels decreased again (HVA: 17.9 ng/mL; MHPG: 7.7 ng/mL). Although
      autoimmune mechanism has been suggested to be involved in HE, neural mechanism
      and pathogenesis of HE remain unknown. Our findings suggest that monoaminergic
      neural activity might be associated with psychotic symptoms in patients with HE
      and plasma levels of monoamine metabolites might be useful as state markers.

PMID- 28435275
TI  - Pathogenic beliefs among patients with depressive disorders.
AB  - INTRODUCTION: Pathogenic belief is a central construct within control-mastery
      theory, which is an integrated dynamic-cognitive-relational approach in
      psychotherapy. Pathogenic beliefs result from traumatic life experiences and are
      considered the root of any psychological disorders presented clinically.
      Nevertheless, how and what type of pathogenic beliefs are attributed to clinical
      depressive disorder is unknown. The present study aimed to examine this issue.
      PATIENTS AND METHODS: Thirty patients with depressive disorder, who came for
      psychotherapy at a psychotherapy clinic, were matched based on age and gender
      with healthy controls who were medical students. The 54-item pathogenic belief
      scale (PBS) was administered and compared between depressive and control groups
      using odds ratio (OR). RESULTS: The depressed group's PBS mean score was
      significantly higher than the healthy controls (t=3.78, P<0.001). Thirteen of 54
      items significantly differed between the two groups with ORs ranging from 3.76 to
      16.79. The content of pathogenic beliefs centered on the issues of negative sense
      of self, lack of self-efficacy and control, and relational difficulties related
      to feelings of fear and humiliation. Influences of culture and gender differences
      on pathogenic beliefs were discussed. CONCLUSION: Pathogenic beliefs relate to
      depression such that the higher the number of pathogenic beliefs one has, the
      more the likelihood of having depression. Since the PBS was developed based on
      clinical data (rather than theory based), cultural issues as well as age and
      gender may influence the development of pathogenic beliefs. Further study should
      be warranted and implications for clinical practice are discussed.

PMID- 28435276
TI  - Clinical and biochemical study of d-serine metabolism among schizophrenia
      patients.
AB  - BACKGROUND: Schizophrenia is a typical N-methyl-d-aspartate receptor (NMDA-R)
      hypofunction disorder. Decreased d-serine (d-Ser) levels in the periphery occur
      in schizophrenia and may reflect decreased availability of d-Ser to activate NMDA
      R in the brain. OBJECTIVE: The objective of this study was to investigate the
      role of d-Ser metabolism in the pathogenesis of schizophrenia via biochemical
      assays and correlates, the serum level of d-Ser, d-serine racemase (SR)
      (responsible for its formation from l-serine [l-Ser]) and d-amino acid oxidase
      (DAAO) (responsible for its catabolism), among different clinical types of
      schizophrenia patients. PATIENTS AND METHODS: This cross-sectional case-control
      study was carried out on 100 patients and 50 controls. They were recruited from
      the outpatients' psychiatric unit of the Neuropsychiatric Department of Assiut
      University Hospital, Upper Egypt. The type of schizophrenia was determined
      according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (DSM-IV), while the severity of schizophrenia was determined according to
      the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
      Serum d-Ser levels were estimated using high-performance liquid chromatography
      (HPLC), while serum SR and DAAO were measured using commercially available enzyme
      linked immunosorbent assay kits. RESULTS: There were significantly lower mean
      serum levels of d-Ser and SR and significantly higher mean serum levels of DAAO
      (P-value <0.01 for each) among schizophrenia patients when compared with the
      control group. Paranoid schizophrenia had the highest frequency, with a
      significantly lower serum levels of d-Ser and SR in the residual type and
      significantly higher serum levels of DAAO in undifferentiated and catatonic
      types. Combined receiver-operating characteristic curve for serum d-Ser, SR and
      DAAO indicated that the best serum level cutoff points at which schizophrenia
      manifestations started to appear were <= 61.4 mg/L for d-Ser, <= 15.5 pg/mL for
      SR and >35.6 pg/mL for DAAO. CONCLUSION: The present study confirms that
      disturbed d-Ser metabolism could be implicated in the pathogenesis of
      schizophrenia.

PMID- 28435277
TI  - Role of pirfenidone in the management of pulmonary fibrosis.
AB  - Pulmonary fibrosis is associated with a number of specific forms of interstitial
      lung disease (ILD) and can lead to progressive decline in lung function, poor
      quality of life, and, ultimately, early death. Idiopathic pulmonary fibrosis
      (IPF), the most common fibrotic ILD, affects up to 1 in 200 elderly individuals
      and has a median survival that ranges from 3 to 5 years following initial
      diagnosis. IPF has not been shown to respond to immunomodulatory therapies, but
      recent trials with novel antifibrotic agents have demonstrated lessening of lung
      function decline over time. Pirfenidone has been shown to significantly slow
      decline in forced vital capacity (FVC) over time and prolong progression-free
      survival, which led to its licensing by the United States Food and Drug
      Administration (FDA) in 2014 for the treatment of patients with IPF. However,
      pirfenidone has been associated with significant side effects, and patients
      treated with pirfenidone must be carefully monitored. We review recent and
      ongoing clinical research and experience with pirfenidone as a pharmacologic
      therapy for patients with IPF, provide a suggested approach to incorporate
      pirfenidone into a treatment algorithm for patients with IPF, and examine the
      potential of pirfenidone as a treatment for non-IPF forms of ILD accompanied by
      progressive pulmonary fibrosis.

PMID- 28435278
TI  - Genetic factors in pathogenesis of diabetes mellitus after kidney
      transplantation.
AB  - Posttransplant diabetes mellitus (PTDM) is one of the major metabolic
      complications after transplantation of solid organs including the kidney. This
      type of diabetes mellitus affects allograft survival, cardiovascular
      complications and overall patient survival. The modifiable risk factors that
      contribute to PTDM include obesity, some viral infections (eg, hepatitis C virus,
      cytomegalovirus) and especially immunosuppressive drugs including
      corticosteroids, tacrolimus, cyclosporine and sirolimus. Currently, predisposing
      genetic factors have been considered important in PTDM development. The commonly
      evaluated genetic determinants include genes encoding transcription factors,
      cytokines, chemokines, adipokines, ionic channels, glucose transporters,
      cytochrome P450 enzymes and other enzymes metabolizing drugs, drug transporters.
      Unfortunately, the results of studies are inconclusive and differ between
      populations. There is a need for large genome-wide association study to identify
      the genetic risk factors associated with PTDM development.

PMID- 28435279
TI  - Use of direct oral anticoagulants for the prevention and treatment of
      thromboembolic disease in patients with reduced renal function: a short review of
      the clinical evidence.
AB  - BACKGROUND: The use of direct oral anticoagulants (DOACs) is restricted by the
      limitations of clinical trials guiding therapy for patients with renal
      impairment, as many of these trials excluded patients with severe renal
      impairment. There are currently four agents available: dabigatran, rivaroxaban,
      apixaban, and edoxaban. The purpose of this review was to 1) describe current
      recommended dosing for each DOAC and published postmarketing data, including case
      reports, on the use of these agents in the renally impaired; and 2) discuss
      patient adherence and satisfaction and the cost of these agents. MATERIALS AND
      METHODS: A literature search was conducted using Medline and Embase with the
      terms "dabigatran" or "rivaroxaban" or "apixaban" or "edoxaban" and "renal
      impairment". Clinical trials and case reports describing the use of DOAC therapy
      in patients with renal impairment were reviewed. A second search was conducted to
      find articles evaluating patient adherence, patient satisfaction, and
      pharmacoeconomics of DOACs. RESULTS: There are a multitude of subgroup and post
      hoc analyses, as well as six case reports with dabigatran and one case report
      with apixaban, that provide insight for the clinical use of DOACs in patients
      with renal impairment. Dabigatran exhibits the greatest level of renal
      elimination, and there are data from clinical trials and several case reports
      that warrant reconsideration before use. Other DOACs may be a better option in
      patients with impaired renal function. Further, data from patient-adherence
      studies have suggested that DOACs that are dosed daily (rather than twice daily)
      are optimal and preferred. There does not appear to be a cost difference between
      DOACs and warfarin therapy. CONCLUSION: DOAC therapy in patients with impaired
      renal function requires more critical review of study data, as these patients may
      have increased risk of bleeding. It is also valuable to consider patient
      preferences and cost when selecting the appropriate option for oral
      anticoagulation.

PMID- 28435280
TI  - High adherence to therapy and low cardiac mortality and morbidity in patients
      after acute coronary syndrome systematically managed by office-based
      cardiologists in Germany: 1-year outcomes of the ProAcor Study.
AB  - We aimed to assess patient acceptance and effectiveness of a 12-month structured
      management program in patients after an acute coronary syndrome (ACS) event who
      were treated in a special setting of office-based cardiologists. The program
      comprised patient documentation with a specific tool (Bundesverband
      Niedergelassener Kardiologen [German Federation of Office-Based Cardiologists]
      cardiac pass with visit scheduling) shared by the hospital physician and the
      office-based cardiologist, the definition of individual treatment targets, and
      the systematic information of patients in order to optimize adherence to therapy.
      Participating centers (36 hospitals, 60 office-based cardiologists) included a
      total of 1,003 patients with ACS (ST-segment elevation myocardial infarction
      [STEMI] 44.3%, non-ST-segment elevation myocardial infarction [NSTEMI] 39.5%,
      unstable angina pectoris [UA] 15.2%, and unspecified 1.0%). During follow-up,
      treatment rates with cardiac medication remained high in all groups, with dual
      antiplatelet therapy in 91.0% at 3 months, 90.0% at 6 months, and 82.8% at 12
      months, respectively. Twelve months after the inclusion, a total of 798 patients
      (79.6%) still participated in the program. Eighteen patients (1.8%) had died
      after discharge from hospital (6 in the STEMI, 12 in the NSTEMI group), while for
      58 the status was unknown (5.8%). Based on a conservative approach that
      considered patients with unknown status as dead, 1-year mortality was 7.6%.
      Recurrent cardiac events were noted in 14.9% at 1 year, with an about equal
      distribution across STEMI and NSTEMI patients. In conclusion, patients'
      acceptance of the ProAcor program as determined by adherence rates over time was
      high. Treatment rates of recommended medications used for patients with coronary
      heart disease were excellent. The 1-year mortality rate was comparatively low.

PMID- 28435281
TI  - First, do no harm: institutional betrayal and trust in health care organizations.
AB  - PURPOSE: Patients' trust in health care is increasingly recognized as important
      to quality care, yet questions remain about what types of health care experiences
      erode trust. The current study assessed the prevalence and impact of
      institutional betrayal on patients' trust and engagement in health care.
      PARTICIPANTS AND METHODS: Participants who had sought health care in the US in
      October 2013 were recruited from an online marketplace, Amazon's Mechanical Turk.
      Participants (n = 707; 73% Caucasian; 56.8% female; 9.8% lesbian, gay, or
      bisexual; median age between 18 and 35 years) responded to survey questions about
      health care use, trust in health care providers and organizations, negative
      medical experiences, and institutional betrayal. RESULTS: Institutional betrayal
      was reported by two-thirds of the participants and predicted disengagement from
      health care (r = 0.36, p < 0.001). Mediational models (tested using bootstrapping
      analyses) indicated a negative, nonzero pathway between institutional betrayal
      and trust in health care organizations (b = -0.05, 95% confidence interval [CI] =
      [-0.07, -0.02]), controlling for trust in physicians and hospitalization history.
      These negative effects were not buffered by trust in one's own physician, but in
      fact patients who trusted their physician more reported lower trust in health
      care organizations following negative medical events (interaction b = -0.02,
      95%CI = [-0.03, -0.01]). CONCLUSION: Clinical implications are discussed,
      concluding that institutional betrayal decreases patient trust and engagement in
      health care.

PMID- 28435282
TI  - Managing the patient with osteogenesis imperfecta: a multidisciplinary approach.
AB  - Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue
      disorder characterized by low bone density. The type and severity of OI are
      variable. The primary manifestations are fractures, bone deformity, and bone
      pain, resulting in reduced mobility and function to complete everyday tasks. OI
      affects not only the physical but also the social and emotional well-being of
      children, young people, and their families. As such, medical, surgical, and
      allied health professionals' assessments all play a role in the management of
      these children. The multidisciplinary approach to the treatment of children and
      young people living with OI seeks to provide well-coordinated, comprehensive
      assessments, and interventions that place the child and family at the very center
      of their care. The coordinated efforts of a multidisciplinary team can support
      children with OI to fulfill their potential, maximizing function, independence,
      and well-being.

PMID- 28435283
TI  - Unlocking the "black box" of practice improvement strategies to implement
      surgical safety checklists: a process evaluation.
AB  - BACKGROUND: Compliance with surgical safety checklists (SSCs) has been associated
      with improvements in clinical processes such as antibiotic use, correct site
      marking, and overall safety processes. Yet, proper execution has been difficult
      to achieve. OBJECTIVES: The objective of this study was to undertake a process
      evaluation of four knowledge translation (KT) strategies used to implement the
      Pass the Baton (PTB) intervention which was designed to improve utilization of
      the SSC. METHODS: As part of the process evaluation, a logic model was generated
      to explain which KT strategies worked well (or less well) in the operating rooms
      of a tertiary referral hospital in Queensland, Australia. The KT strategies
      implemented included change champions/opinion leaders, education, audit and
      feedback, and reminders. In evaluating the implementation of these strategies,
      this study considered context, intervention and underpinning assumptions,
      implementation, and mechanism of impact. Observational and interview data were
      collected to assess implementation of the KT strategies relative to fidelity,
      feasibility, and acceptability. RESULTS: Findings from 35 structured observations
      and 15 interviews with 96 intervention participants suggest that all of the KT
      strategies were consistently implemented. Of the 220 staff working in the
      department, that is, nurses, anesthetists, and surgeons, 160 (72.7%) knew about
      the PTB strategies. Qualitative analysis revealed that implementation was
      generally feasible and acceptable. A barrier to feasibility was physician
      engagement. An impediment to acceptability was participants' skepticism about the
      ability of the KT strategies to effect behavioral change. CONCLUSION: Overall,
      results of this evaluation suggest that success of implementation was moderate.
      Given the probable impact of contextual factors, that is, team culture and the
      characteristics of participants, the KT strategies may need modification prior to
      widespread implementation.

PMID- 28435284
TI  - Clinical significance of serum cathepsin B and cystatin C levels and their ratio
      in the prognosis of patients with esophageal cancer.
AB  - OBJECTIVE: The main purpose of this study was to analyze the serum cathepsin B
      (CTSB) and cystatin C (CysC) levels in patients with esophageal carcinoma and
      their correlation with the clinical indices and prognosis. METHODS: The serum
      levels of CTSB and CysC from 56 patients with esophageal carcinoma and 30 healthy
      donors were determined preoperatively by using enzyme-linked immunosor-bent
      assay. The correlation between CTSB and CysC was evaluated by Spearman
      correlation coefficient test. Kaplan-Meier survival curves were plotted, while
      the survival rates were compared using the log-rank test. Univariate and
      multivariate analyses of prognostic factors for survival were performed using the
      Cox proportional hazard regression model with a 95% confidence interval. RESULTS:
      CTSB (38.35+/-4.3 ng/mL) and CysC (703.96+/-23.6 ng/mL) levels were significantly
      higher in the sera of the patients than in controls. A significant correlation
      was observed between CTSB and CysC (r=0.754, P<0.001). The levels of CTSB and
      CysC/CTSB in the patient serum significantly correlated with the T status.
      CysC/CTSB ratio was also found to be significantly correlated with lymph node
      metastasis. None of the parameters were observed to be related to CysC, including
      age, gender, pathologic type, tumor differentiation and tumor invasion depth.
      Kaplan-Meier analysis showed that patients with higher levels of CysC/CTSB and
      negative lymph node metastasis experienced significantly longer overall survival
      time, whereas patients with higher CSTB levels tended to live shorter, although
      the difference was not statistically significant (P=0.081). CONCLUSION: Serum
      CTSB and CysC levels are of diagnostic significance in esophageal cancer. The
      ratio of serum CysC/CTSB is prognostic for the survival of esophageal carcinoma
      patients.

PMID- 28435285
TI  - Exploratory cohort study and meta-analysis of BIM deletion polymorphism in
      patients with epidermal growth factor receptor-mutant non-small-cell lung cancer
      treated with epidermal growth factor receptor tyrosine kinase inhibitors.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC) patients with epidermal growth
      factor receptor (EGFR) mutations might develop primary and secondary resistance
      to tyrosine kinase inhibitors (TKIs). The proapoptotic protein Bcl-2-like 11
      (BIM) is a key modulator of apoptosis triggered by EGFR-TKIs. The recent studies
      have indicated that some patients with positive EGFR mutations were refractory to
      EGFR-TKIs if they harbored a BIM deletion polymorphism. The purpose of this study
      was to investigate whether BIM polymorphism predicts treatment efficacy of EGFR
      TKIs in Chinese NSCLC patients. PATIENTS AND METHODS: A cohort of advanced NSCLC
      patients with EGFR mutations and treated with EGFR-TKIs (gefitinib or erlotinib)
      were recruited. We drew peripheral blood to determinate BIM deletion status and
      then compared patients' clinical outcomes according to the BIM deletion status.
      Additionally, we electronically searched eligible cohort studies and conducted a
      meta-analysis to pool event risk. RESULTS: The exploratory cohort study included
      140 patients. Patients with and without the BIM deletion polymorphism had similar
      objective response rates (ORRs, 48.5 vs 63.0%, P=0.16), disease control rate
      (DCR, 93.9 vs 97.0%, P=0.60) and adverse reactions. Similar progression-free
      survival (PFS) and overall survival (OS) were noted in overall population (P=0.27
      for PFS and P=0.61 for OS) and prespecified patient subgroups. The meta-analysis
      included 10 eligible cohort studies involving 1,317 NSCLC patients. It showed the
      positive BIM deletion was associated with shorter PFS (hazard ratio =1.45;
      P=0.02). Nonsignificant differences existed for ORR, DCR and OS. CONCLUSION: The
      expanded meta-analysis results demonstrated the positive BIM deletion predicts
      shorter PFS in NSCLC patients after treatment with EGFR-TKIs while other clinical
      measures do not. A large multicenter well-designed cohort study involving other
      concurrent genetic alterations is warranted.

PMID- 28435286
TI  - HSD17B12 gene rs11037575 C>T polymorphism confers neuroblastoma susceptibility in
      a Southern Chinese population.
AB  - A previous genome-wide association study (GWAS) identified four genetic
      polymorphisms (rs1027702 near DUSP12, rs10055201 in IL31RA, rs2619046 in DDX4,
      and rs11037575 in HSD17B12 gene) that were associated with neuroblastoma
      susceptibility, especially for low-risk subjects. The aim of this study was to
      examine the association between these four polymorphisms and neuroblastoma
      susceptibility in a Southern Chinese population composed of 256 cases and 531
      controls. Overall, among all the polymorphisms, single-locus analysis only
      revealed significant association between the HSD17B12 rs11037575 C>T polymorphism
      and neuroblastoma susceptibility (CT vs CC: adjusted odds ratio [OR] =0.71, 95%
      confidence interval [CI] =0.51-0.97, P=0.030). Moreover, stratified analysis
      indicated that the rs11037575 T allele was associated with decreased
      neuroblastoma risk among the children aged 0-18 months (adjusted OR =0.60, 95% CI
      =0.37-0.97, P=0.036); regarding the tumor site, this polymorphism protected
      against tumor in the mediastinum (adjusted OR =0.59, 95% CI =0.37-0.94, P=0.025).
      When risk genotypes were combined, we found that girls with two to four risk
      genotypes were at a significantly increased risk of neuroblastoma (adjusted OR
      =1.65, 95% CI =1.03-2.64, P=0.039). In terms of clinical stages, individuals with
      two to four risk genotypes had a tendency toward the development of stage III/IV
      diseases (adjusted OR =1.69, 95% CI =1.12-2.54, P=0.012). In conclusion, we
      verified that the HSD17B12 rs11037575 T allele might negatively associate with
      neuroblastoma risk. These findings need further validation by prospective studies
      with larger sample size and different ethnicities.

PMID- 28435287
TI  - Serum galectin-1 in patients with multiple myeloma: associations with survival,
      angiogenesis, and biomarkers of macrophage activation.
AB  - Galectin-1 (Gal-1) is known to regulate cell signaling within the immune system
      and may be a target for new anticancer immune therapy. In patients with chronic
      lymphocytic leukemia (CLL) and classical Hodgkin lymphoma (cHL), high levels of
      Gal-1 within the tumor microenvironment were associated with worse disease state
      or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and
      levels in blood samples were associated with high tumor burden and worse disease
      state in cHL and CLL patients. However, serum levels of Gal-1 have never been
      investigated in patients with multiple myeloma (MM). We measured serum Gal-1
      levels in samples from patients with treatment demanding MM at the time of
      diagnosis (n=102) and after treatment (n=24) and examined associations of serum
      Gal-1 with clinicopathological information obtained from patient medical records,
      as well as data on bone marrow angiogenesis and the macrophage activation
      biomarkers soluble CD163 (sCD163) and soluble mannose receptor. Serum Gal-1
      levels were not elevated in patients with MM at diagnosis compared with healthy
      donors (median values 8.48 vs 11.93 ng/mL, P=0.05), which is in contrast to
      results in cHL and CLL. Furthermore, Gal-1 levels did not show association with
      bone marrow angiogenesis, clinicopathological parameters, overall survival, or
      response to treatment. There was a statically significant association between Gal
      1 and sCD163 levels (R=0.24, P=0.02), but not with soluble mannose receptor
      (P=0.92). In conclusion, our results indicate that Gal-1 is not an important
      serum biomarker in MM, which is in contrast to data from patients with cHL and
      CLL. However, the association with sCD163 is in line with previous data showing
      that Gal-1 may be involved in alternative (M2-like) activation of macrophages.

PMID- 28435288
TI  - The activity, safety, and evolving role of brigatinib in patients with ALK
      rearranged non-small cell lung cancers.
AB  - Brigatinib (AP26113) is a dimethylphosphine oxide group-containing tyrosine
      kinase inhibitor (TKI) constructed around a bisanilinopyrimidine scaffold with
      potent activity against the anaplastic lymphoma kinase (ALK) and several other
      targets. Despite the activity of first- and second-generation ALK inhibitors in
      advanced ALK-rearranged lung cancers, the development of acquired resistance
      represents an ongoing challenge. Later generation ALK inhibitors such as
      brigatinib are important potential tools in the management of patients with
      acquired resistance characterized by continued dependency on ALK. Brigatinib is
      active in vitro against many ALK kinase domain mutations that may mediate
      acquired resistance to other ALK TKIs, with reported activity (IC50 <50 nM)
      against ALK C1156Y, I1171S/T, V1180L, L1196M, L1152R/P, E1210K, and G1269A. In
      patients with ALK-rearranged lung cancers who receive brigatinib after
      crizotinib, substantial and durable responses and intracranial disease control
      can be achieved based on early-phase clinical trial data. The drug is also being
      explored in TKI-naive patients. From a safety perspective, early pulmonary
      toxicity has been observed, prompting the decision to pursue lead-in dosing for
      the drug. Early data point to ALK G1202R and ALK E1210K as potential mechanisms
      of clinical resistance to brigatinib.

PMID- 28435289
TI  - Long noncoding RNA NBAT-1 suppresses tumorigenesis and predicts favorable
      prognosis in ovarian cancer.
AB  - Long noncoding RNA (lncRNA) has been proven to be involved in many biological
      processes in ovarian cancer (OC). However, the mechanism still remains unknown.
      In this study, we screened significantly downregulated NBAT-1, which has been
      proven to play a significant role in breast cancer, clear cell renal cell
      carcinoma, and neuroblastoma, but not in OC, in two independent datasets with
      relatively more samples (GSE18520 and GSE38666) from Gene Expression Omnibus. We
      found that lncRNA NBAT-1 was obviously downregulated in OC tissue compared to
      normal ovarian tissue (P<0.001) which was free of OC, and the detected levels of
      NBAT-1 were associated with the International Federation of Gynecology and
      Obstetrics stage and tumor size guidelines. Moreover, it has been shown that
      lower levels of NBAT-1 predict poor outcomes of OC. In order to investigate the
      functional role of NBAT-1, pcDNA-NBAT-1 and empty vector were transfected into
      TOV112D and OVCAR-3 cell lines. Overexpressed NBAT-1 significantly inhibited cell
      proliferation, invasion, and migration in both TOV112D and OVCAR-3 cell lines.
      Finally, Western blot assay indicated that NBAT-1 may exert its function by
      targeting the ERK1/2 and AKT signaling pathways. In addition, tumor formation
      growth assay showed that overexpressed NBAT-1 significantly suppresses tumor
      growth in vivo. In conclusion, our study suggests that NBAT-1 acts as an anti
      oncogene in the development of OC.

PMID- 28435290
TI  - Altered status of programmed death-ligand 1 after recurrence in resected lung
      adenocarcinoma patients.
AB  - PURPOSE: Programmed death-ligand 1 (PD-L1) is found to be overexpressed in non
      small cell lung cancer. The present study intended to evaluate the status of PD
      L1 expression in patients with resection and recurrent lung adenocarcinoma.
      PATIENTS AND METHODS: Matched resection and recurrent tumor samples were
      harvested from 65 lung adenocarcinoma patients. Immunohistochemistry was used to
      evaluate the status of PD-L1 expression. Kaplan-Meier method was used for
      survival analysis. RESULTS: A total of 65 patients of lung adenocarcinoma were
      enrolled. They underwent complete resection and had recurrence after adjuvant
      treatment. PD-L1 expression was identified in 43.1% (28/65) of resection samples
      vs 55.4% (36/65) of recurrent samples. Ten patients shifted from negative to
      positive, whereas another two samples showed the opposite. Patients with PD-L1
      expression showed worse disease-free survival than the PD-L1-negative
      counterparts. The expression of PD-L1 in recurrent samples was a significant
      favorable factor for epidermal growth factor receptor tyrosine kinase inhibitors
      (EGFR-TKIs) (11.2 vs 8.2 months, P=0.030). CONCLUSION: The status of PD-L1
      expression may alter between resection and recurrent samples. Also, the status of
      PD-L1 expression after recurrence is a better prognostic factor for EGFR-TKIs.

PMID- 28435291
TI  - Role of postmastectomy radiotherapy in early-stage (T1-2N0-1M0) triple-negative
      breast cancer: a systematic review.
AB  - Triple-negative breast cancer (TNBC), which represents 15%-20% of all breast
      cancers, is defined by the absence of estrogen receptor (ER) and progesterone
      receptor (PR) and overexpression of human epidermal growth factor receptor 2
      (HER2). Owing to the absence of specific therapeutic targets and its aggressive
      biologic characteristics, TNBC patients often experience a high risk of disease
      progression and poor overall survival. Furthermore, TNBC exhibits an early
      pattern of recurrence with a peak recurrence risk at 2-3 years after surgery.
      Currently, chemotherapy continues to be the mainstay in TNBC patients; however,
      such treatment leaves them associated with a high rate of local and systemic
      relapses even in early-stage (T1-2N0-1M0). Therefore, in early-stage disease,
      greater emphasis is placed on locoregional treatments, based on radiation therapy
      (RT) after surgery, to reduce local and systemic relapses. However, there are no
      specific treatment guidelines for early-stage (T1-2N0-1M0) TNBC patients. In this
      review, we discuss the type of surgery received and the relevant adverse
      clinicopathologic factors and underlying BRCA1 mutation status regarding the
      influence of tailing postmastectomy radiotherapy (PMRT). In addition, we assess
      the role of PMRT in early-stage (T1-2N0-1M0) TNBC patients.

PMID- 28435292
TI  - REG3A promotes the proliferation, migration, and invasion of gastric cancer
      cells.
AB  - The mechanism underlying the metastasis of gastric cancer (GC) cells remains
      elusive. REG3A is considered an oncogene in various cancers, but in GC its role
      is unclear. Here, we report that the expression of REG3A was significantly
      increased in the tumor tissues of patients with GC compared with the matched
      normal tissues. Knockdown of REG3A induced by specific small interfering RNA
      (siRNA) significantly repressed the proliferation of GC cells for 24 h or 48 h.
      Moreover, knockdown of REG3A significantly suppressed the migration, invasion,
      and adhesion of GC cells in vitro. Furthermore, knockdown of REG3A reduced the
      phosphorylation of JAK2 and STAT3, and altered the messenger RNA (mRNA) and
      protein expression levels of E-cadherin, Snail, RhoC, MTA1, MMP-2, and MMP-9.
      Taken together, REG3A is overexpressed in GC and promotes the proliferation,
      migration, invasion, and adhesion of GC cells by regulating the JAK2/STAT3 signal
      pathway. REG3A may be a potential therapeutic target for GC.

PMID- 28435293
TI  - Expression and significance of GRHL2 in esophageal cancer.
AB  - Esophageal cancer (EC) is one of the most common causes of cancer-related
      mortality in the world. Although much effort has been made to improve the 5-year
      survival rate of patients with EC, it still remains low due to diagnosis at an
      advanced stage, aggressive local invasion, early metastasis, and resistance to
      chemotherapy. Although grainyhead-like 2 (GRHL2) has attracted interest since it
      has been recently identified as a novel suppressor of the epithelial-mesenchymal
      transition, clinical values of GRHL2 and its relationship with the metastasis
      related factors, such as hypoxia-inducible factor 1alpha (HIF-1alpha) and
      vascular endothelial growth factor (VEGF), remain unclear. In order to
      investigate the expression of GRHL2, HIF-1alpha, and VEGF, and their correlation
      with angiogenesis in EC, 63 patients with EC were examined. The expression of
      GRHL2, HIF-1alpha, and VEGF in tumor tissues was higher than that in adjacent
      tissues and was associated with tumor differentiation. GRHL2 expression was
      significantly correlated with lymph node metastasis and invasion depth, whereas
      VEGF expression was associated with tumor (TNM) stage. A significant correlation
      was found between the expression of GRHL2 and HIF-1alpha. The patients expressing
      low GRHL2 and high HIF-1alpha showed significant reduction in both overall
      survival rate and disease-free survival rate. The results demonstrated that
      abnormal expression of GRHL2 is common in EC, and low expression of GRHL2
      accompanied by a high expression of HIF-1alpha indicates poor prognosis.

PMID- 28435294
TI  - Patient considerations in metastatic colorectal cancer - role of panitumumab.
AB  - Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies,
      including colorectal cancer (CRC), making EGFR an attractive treatment option.
      Panitumumab and cetuximab, monoclonal antibodies (mAbs) directed at EGFR, are
      both currently utilized in the management of metastatic CRC (mCRC). Through the
      development of these agents in mCRC, key issues surrounding each mAbs use have
      been revealed. These key issues include negative patient outcome avoidance when
      determining use, the economic burden with high-cost medication, predictive
      biomarkers, tumor location, patient geographic location, patient quality of life,
      and the prevention of debilitating adverse effects. CRC remains a common
      malignancy, with many of these patients expected to receive targeted therapy,
      including EGFR mAb therapy. Oncologists must recognize these EGFR mAb factors in
      order to improve outcomes. This review aims to provide a chronological timeline
      on the development of panitumumab, clinical pearls, and guidance on the current
      use of panitumumab in mCRC.

PMID- 28435295
TI  - Silencing CDR1as inhibits colorectal cancer progression through regulating
      microRNA-7.
AB  - An increasing number of studies have demonstrated that circular RNAs (circRNAs)
      can regulate gene expression through interacting with microRNAs. In this study,
      we analyzed the expression of antisense to CDR1as in colorectal cancer (CRC).
      CDR1as had a higher expression in CRC tissues compared to adjacent, normal mucosa
      and was positively associated with tumor size, T stage, lymph node metastasis,
      and poor overall survival (OS). Downregulation of CDR1as suppressed CRC cell
      proliferation and invasion and increased microRNA-7 (miR-7) expression.
      Intriguingly, ectopic expression of miR-7 in CRC cells consistently inhibited
      proliferation and invasion, and the miR-7 inhibitor was able to rescue the
      function of CDR1as knockdown. Mechanistic studies demonstrated that CDR1as
      silencing suppressed EGFR and IGF-1R expression, which could be partially blocked
      by the miR-7 inhibitor. Finally, positive correlations between CDR1as expression
      and EGFR and IGF-1R expression were observed in CRC samples. Thus, given the
      importance of CDR1as in blocking miR-7 and positively regulating EGFR and IGF-1R,
      dysregulated CDR1as expression may play an important role in CRC progression.

PMID- 28435296
TI  - Spotlight on bevacizumab and its potential in the treatment of malignant pleural
      mesothelioma: the evidence to date.
AB  - Malignant pleural mesothelioma (MPM) is a rare, but aggressive cancer. Surgery
      and radiation offer limited benefit, and systemic chemotherapy remains the
      primary treatment modality for the majority of patients. Vascular endothelial
      growth factor (VEGF) and its receptor have been recognized as important players
      in the biology of this disease. Bevacizumab is a monoclonal antibody that binds
      VEGF and blocks its interaction with the VEGF receptor. Recent studies have shown
      benefit with the addition of bevacizumab to the combination of cisplatin and
      pemetrexed in MPM. This combination is now included in the National Comprehensive
      Cancer Network guidelines (with a category 2A recommendation) as a possible first
      line treatment for unresectable MPM in appropriately selected patients. This
      review discusses the rationale behind the use of bevacizumab in MPM, as well as
      summarizes the pharmacology, efficacy, safety, and toxicity of bevacizumab across
      multiple trials. The use of small-molecule inhibitors of angiogenesis in the
      treatment of MPM is also discussed.

PMID- 28435297
TI  - The role of KPNbeta1 in neuro-oncology.

PMID- 28435298
TI  - Therapeutic outcome of nasopharyngeal carcinoma with cranial nerve palsy: a
      single institution experience of 104 patients.
AB  - PURPOSE: Cranial nerve (CN) palsy is the main symptom in patients with locally
      advanced nasopharyngeal carcinoma (NPC). This study aimed to evaluate the
      therapeutic outcome of NPC with CN palsy and to analyze the prognostic factors.
      PATIENTS AND METHODS: A total of 104 NPC patients with CN palsy curatively
      treated by conventional (n=44) or conformal (n=60) radiotherapy (RT) were
      enrolled. Upper CN palsy was present in 81 patients, lower CN palsy in four
      patients, and both upper and lower CN palsy in 19 patients. Forty-one patients
      had CN palsy for >2 months before diagnosis. RESULTS: Complete recovery of CN
      palsy was observed in 74 patients. The actuarial 5-year locoregional control
      (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates
      were 58.2%, 62.2%, and 38.4%, respectively. No significant difference was
      observed in CN recovery, LRC, DMFS, or OS for patients treated by conventional
      versus conformal technique. However, significant reduction of grade 3 or greater
      toxicities was found in those treated by the conformal technique (odds ratio
      =0.28). CONCLUSION: Patients with CN palsy presenting >2 months before diagnosis
      were hard to recover from palsy. The LRC, OS, and recovery from CN palsy did not
      significantly change with the treatment evolution. Patients with complete
      recovery from CN palsy had longer OS.

PMID- 28435299
TI  - Genetic interrelations in the actinomycin biosynthetic gene clusters of
      Streptomyces antibioticus IMRU 3720 and Streptomyces chrysomallus ATCC11523,
      producers of actinomycin X and actinomycin C.
AB  - Sequencing the actinomycin (acm) biosynthetic gene cluster of Streptomyces
      antibioticus IMRU 3720, which produces actinomycin X (Acm X), revealed 20 genes
      organized into a highly similar framework as in the bi-armed acm C biosynthetic
      gene cluster of Streptomyces chrysomallus but without an attached additional
      extra arm of orthologues as in the latter. Curiously, the extra arm of the S.
      chrysomallus gene cluster turned out to perfectly match the single arm of the S.
      antibioticus gene cluster in the same order of orthologues including the the
      presence of two pseudogenes, scacmM and scacmN, encoding a cytochrome P450 and
      its ferredoxin, respectively. Orthologues of the latter genes were both missing
      in the principal arm of the S. chrysomallus acm C gene cluster. All orthologues
      of the extra arm showed a G +C-contents different from that of their counterparts
      in the principal arm. Moreover, the similarities of translation products from the
      extra arm were all higher to the corresponding translation products of orthologue
      genes from the S. antibioticus acm X gene cluster than to those encoded by the
      principal arm of their own gene cluster. This suggests that the duplicated
      structure of the S. chrysomallus acm C biosynthetic gene cluster evolved from
      previous fusion between two one-armed acm gene clusters each from a different
      genetic background. However, while scacmM and scacmN in the extra arm of the S.
      chrysomallus acm C gene cluster are mutated and therefore are non-functional,
      their orthologues saacmM and saacmN in the S. antibioticus acm C gene cluster
      show no defects seemingly encoding active enzymes with functions specific for Acm
      X biosynthesis. Both acm biosynthetic gene clusters lack a kynurenine-3
      monooxygenase gene necessary for biosynthesis of 3-hydroxy-4-methylanthranilic
      acid, the building block of the Acm chromophore, which suggests participation of
      a genome-encoded relevant monooxygenase during Acm biosynthesis in both S.
      chrysomallus and S. antibioticus.

PMID- 28435300
TI  - The identification of protein domains that mediate functional interactions
      between Rab-GTPases and RabGAPs using 3D protein modeling.
AB  - Currently, time-consuming serial in vitro experimentation involving
      immunocytochemistry or radiolabeled materials is required to identify which of
      the numerous Rab-GTPases (Rab) and Rab-GTPase activating proteins (RabGAP) are
      capable of functional interactions. These interactions are essential for numerous
      cellular functions, and in silico methods of reducing in vitro trial and error
      would accelerate the pace of research in cell biology. We have utilized a
      combination of three-dimensional protein modeling and protein bioinformatics to
      identify domains present in Rab proteins that are predictive of their functional
      interaction with a specific RabGAP. The RabF2 and RabSF1 domains appear to play
      functional roles in mediating the interaction between Rabs and RabGAPs. Moreover,
      the RabSF1 domain can be used to make in silico predictions of functional
      Rab/RabGAP pairs. This method is expected to be a broadly applicable tool for
      predicting protein-protein interactions where existing crystal structures for
      homologs of the proteins of interest are available.

PMID- 28435301
TI  - Egg introduction: differential allergic responses.
AB  - The use of egg protein preparations in clinical trials to reduce the incidence of
      egg allergy among infants includes a number of preparations of egg. These include
      whole egg, egg white protein, and egg yolk preparations. The study of the
      differential immune responses to these allergenic proteins in comparison is
      suggested as a future research area of investigation.

PMID- 28435302
TI  - In situ detection of Chlamydia pneumoniae, C. trachomatis, and cytokines among
      cardiovascular diseased patients from the Amazon region of Brazil.
AB  - BACKGROUND: Chronic coronary artery disease has been associated, as a consequence
      of the local inflammatory reaction with previous or persistent infection with
      Chlamydia pneumoniae, which led to the investigation of the association of
      cardiovascular disease and previous infection with C. trachomatis and the role of
      cytokine profile (in situ) markers in the vascular system tissues. METHODS: Sixty
      nine biopsies were collected for immunohistochemical analysis for the presence of
      IL-6, IL-8, TNF-alpha, IFN-gamma, TGF-beta, and IL-10, in 16 fragments from
      atheromatous plaques, 32 aorta fragments, and 21 valve fragments, using a tissue
      microarray technique for paraffin embedded tissues. RESULTS: Most patients
      undergoing revascularization surgery were men >50 years, while those undergoing
      valve replacement were mostly women <50 years. TNF-alpha was the most prevalent
      marker, detected in 91.7% (55/60) of the samples. The mean percent area stained
      was greater in patients infected with C. pneumoniae (3.81% vs 1.92%; p=0.0115)
      and specifically in the aorta (4.83% vs 2.25%; p=0.0025); C. trachomatis
      infection was higher in valves, and C. pneumoniae in plaques, both without
      statistical significance. There was no significant difference in the cytokine
      staining profile between patients previously infected with both species and
      uninfected patients. CONCLUSION: Although there was no difference in the cytokine
      profile between patients previously infected with both species of Chlamydia, and
      uninfected patients, the presence of the bacteria antigens in the three
      biological specimens indicates it is important to focus on the role of C.
      trachomatis. It is necessary to improve the understanding of the natural history
      of chronic coronary artery disease and the clinical history of the patients and
      cytokine dynamics in cardiac disease in the presence or absence of infectious
      agents.

PMID- 28435303
TI  - Economic benefit of back titration in the treatment of hypertension in Jos,
      Nigeria.
AB  - PURPOSE: Treatment of hypertension is expensive and cost is one of the reasons
      for inadequate blood pressure control. Where there are no social cost cushions,
      the burden is borne by patients. With pervasive poverty and inadequate control,
      complications are unchecked. Back titration in appropriate circumstances should,
      therefore, translate to economic benefit. This is an attempt to compute, in
      economic terms, the benefit of back titration. PATIENTS AND METHODS: Thirty-nine
      patients who entered an antihypertensive back titration program for 12 months and
      who had been earlier reported on, form the subject of this study. A survey of the
      cost of antihypertensives in pharmacy outlets in Jos, Nigeria was undertaken.
      Regimens of antihypertensives that patients were on at the onset and end of the
      12 months of back titration were costed in Nigerian currency and compared.
      RESULTS: Back titration translated to economic benefit in all patients with a
      cost reduction varying from 2.3% to 100%. This reflected in reduction in mean
      daily cost of treatment of N107.09-N54.61. CONCLUSION: The benefit of
      antihypertensive back titration apart from psychological relief of lower pill
      burden and side effect profile is in pharmacoeconomics. This permits greater
      adherence and prevents morbi-mortality consequences of hypertension. In this
      study, back titration over 12 months translated to average cost reduction of
      >50%, making treatment more affordable. In appropriate circumstances, back
      titration of antihypertensives results in economic relief for patients. This
      should improve adherence, reduce morbi-mortality and is recommended for wider
      application.

PMID- 28435304
TI  - Comparative effectiveness of glycemic control in patients with type 2 diabetes
      treated with GLP-1 receptor agonists: a network meta-analysis of placebo
      controlled and active-comparator trials.
AB  - BACKGROUND: Clinical studies of patients with type 2 diabetes show that GLP-1
      receptor agonists (GLP-1 RAs) improve glycemic control and promote weight loss.
      We conducted a Bayesian network meta-analysis (NMA) of placebo- and active
      controlled randomized trials to assess the comparative effectiveness of
      liraglutide, albiglutide, dulaglutide, and exenatide twice daily and once weekly,
      with a focus on glycemic control. MATERIALS AND METHODS: We searched Medline,
      Embase, and the Cochrane Library (up to December 2014) for core registration
      programs for US-approved GLP-1 RAs. Patients reaching an A1C target of <7% were
      analyzed with a binomial model and change in A1C from baseline with a normal
      model. A covariate analysis assessed the impact of baseline A1C and treatment
      background on outcomes. RESULTS: The base-case NMA used 23 trials reporting A1C
      outcomes at ~6 month follow-up. The results, unadjusted and adjusted for baseline
      A1C, indicated that all GLP-1 RAs resulted in statistically significantly lower
      A1C at follow-up compared with placebo. The odds of reaching the <7% target were
      also significantly better compared with placebo. With dulaglutide, exenatide once
      weekly, and liraglutide, the absolute reduction in A1C at 6 months was 0.9%-1.4%,
      and was significantly better than exenatide twice daily. Albiglutide was not
      significantly different from exenatide twice daily. We estimate that ~50% of
      patients will meet the <7% A1C target within 6 months of commencing GLP-1 RAs.
      CONCLUSION: This was a comprehensive assessment of the comparative effectiveness
      of GLP-1 RAs and A1C outcome. GLP-1 RAs are a viable addition to oral
      antidiabetes therapy, and dulaglutide, exenatide once weekly, and liraglutide are
      the most effective.

PMID- 28435305
TI  - Glucagon-like peptide-1 receptor agonists: a systematic review of comparative
      effectiveness research.
AB  - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by
      increasing insulin secretion, decreasing glucagon secretion, slowing gastric
      emptying, and increasing satiety. OBJECTIVE: Published evidence directly
      comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was
      systematically reviewed. METHODS: A literature search was performed using MEDLINE
      and Embase databases to identify papers comparing GLP-1RAs with other classes of
      glucose-lowering therapy in patients with T2D. RESULTS: Of the 1303 papers
      identified, 57 met the prespecified criteria for a high-quality clinical trial or
      retrospective study. The efficacy and tolerability of approved GLP-1RAs
      (exenatide twice daily or once weekly, dulaglutide, liraglutide, lixisenatide,
      and albiglutide) were compared with insulin products (23 prospective studies +
      seven retrospective studies), dipeptidyl peptidase-4 inhibitors (11 prospective
      studies + three retrospective studies), sulfonylureas (nine prospective studies +
      one retrospective study), thiazolidinediones (five prospective studies), and
      metformin (two prospective studies). GLP-1RAs are effective as a second-line
      therapy in improving glycemic parameters in patients with T2D. Reductions in
      glycated hemoglobin from baseline with GLP-1RAs tended to be greater or similar
      compared with insulin therapy. GLP-1RAs were consistently more effective in
      reducing body weight than most oral glucose-lowering drugs and insulin and were
      associated with lower hypoglycemia risk versus insulin or sulfonylureas. GLP-1RAs
      improved cardiovascular risk factors, and preliminary data suggest they improve
      cardiovascular outcomes in patients with T2D compared with oral glucose-lowering
      drugs. However, results from ongoing studies are awaited to confirm these early
      findings. CONCLUSION: This systematic review found that GLP-1RAs are an effective
      class of glucose-lowering drugs for T2D.

PMID- 28435306
TI  - Pediatric acute kidney injury: prevalence, impact and management challenges.
AB  - The incidence of pediatric acute kidney injury (AKI) is increasing globally, as
      are the associated morbidities and mortality. A recent standardization of the
      definition of AKI has allowed for a more accurate assessment of the epidemiology
      of pediatric AKI. Recent advances in leveraging electronic medical health record
      systems have allowed for real-time risk stratification and prevention of
      pediatric AKI in the hospital setting. Newly developed and validated clinical
      scores have improved our ability to predict AKI and provide a rational context
      for biomarker utilization in hospitalized children. Novel non-invasive diagnostic
      and predictive biomarkers have been launched globally to improve our ability to
      diagnose and predict AKI and its adverse outcomes as well as recovery. This
      review summarizes the most current literature, focusing on the epidemiology,
      management, and early diagnostic strategies in pediatric AKI.

PMID- 28435307
TI  - Comparison of CYP2C9, CYP2C19, CYP2D6, ABCB1, and SLCO1B1 gene-polymorphism
      frequency in Russian and Nanai populations.
AB  - BACKGROUND: The efficiency and safety of drug therapy depends on the
      peculiarities of functioning of the P450 cytochrome group and transporting
      proteins. There are significant differences for single-nucleotide polymorphism
      (SNP) frequency. MATERIALS AND METHODS: We studied the peculiarities of P450
      cytochrome polymorphisms, SLCO1B1 transporting protein, and P-glycoprotein
      carriage in healthy volunteers in the Nanai ethnic group living in Russia, and
      compared them to the carriage of SNPs in the Russian population according to
      literature data. RESULTS: After performing the real-time polymerase chain
      reactions on the samples from 70 healthy volunteers from the Nanai group, for the
      CYP2C9*2C430T polymorphism we determined 70 CC-genotype carriers. As for the
      CYP2C9*3A1075C polymorphism, we found 62 AA-genotype carriers and eight AC
      genotype carriers. For the CYP2C19*2G681A polymorphism, we determined 39 GG
      genotype carriers and 28 GA-genotype carriers, for the CYP2C19*3G636A
      polymorphism 58 GG-genotype carriers and 12 GA-genotype carriers, and for the
      CYP2C19*17C806T polymorphism 67 CC-genotype carriers and three CT-genotype
      carriers. For the CYP2D6*4G1846A polymorphism, the GG genotype had 68 carriers,
      and the GA genotype two carriers. For the ABCB1*6C3435T polymorphism, there were
      19 CC-genotype carriers and 39 CT-genotype carriers. For the SLCO1B1*5T521C
      polymorphism, the TT genotype had 41 carriers and the CT genotype 25 carriers.
      The distribution of genotypes fitted the Hardy-Weinberg equilibrium for all the
      polymorphisms, except those of CYP2C9*2. There were also significant differences
      in allele frequencies for some polymorphisms between the Nanais and the Russians.
      CONCLUSION: In the Nanai population, there are polymorphisms connected with the
      decrease in safety and efficiency of drug therapy. Studying the ethnic
      differences might influence the determination of priority in the introduction of
      pharmacogenetic tests in clinical practice in different regions of Russia.

PMID- 28435308
TI  - Association of the PPP3CA c.249G>A variant with clinical outcomes of tacrolimus
      based therapy in kidney transplant recipients.
AB  - BACKGROUND: The effects of genetic variants related to the pharmacodynamic
      mechanisms of immunosuppressive drugs on their therapeutic efficacy and safety
      have been poorly explored. This study was performed to investigate the influence
      of the PPP3CA c.249G>A variant on the clinical outcomes of kidney transplant
      recipients. PATIENTS AND METHODS: A total of 148 Brazilian patients received
      tacrolimus (TAC)-based immunosuppressive therapy for 90 days post-kidney
      transplantation. The PPP3CA rs3730251 (c.249G>A) polymorphism was determined by
      real-time polymerase chain reaction. Single-nucleotide polymorphism (SNP) data
      for CYP3A5 rs776746 (CYP3A5*3C; g.6986A>G) were used to eliminate the confounding
      effects of this variant. RESULTS: The PPP3CA c.249G>A SNP did not influence early
      TAC exposure, renal function, or other laboratory parameters, including levels of
      urea, creatinine, glucose, and lipids, and blood counts. This variant also did
      not account for the cumulative incidence of biopsy-confirmed acute rejection or
      delayed graft function. Regarding adverse events, PPP3CA c.249A allele carriers
      initially had a 3.05-fold increased probability of treatment-induced blood and
      lymphatic system disorders compared with c.249GG genotype individuals (95%
      confidence interval: 1.10-8.48, p=0.032). However, this result was not maintained
      after adjusting for body weight and CYP3A5*3C SNP status (p=0.086). CONCLUSION:
      The PPP3CA c.249G>A variant does not influence the clinical outcomes of Brazilian
      patients in the early phase of TAC-based immunosuppressive regimen.

PMID- 28435309
TI  - Recognition and management of platelet-refractory bleeding in patients with
      Glanzmann's thrombasthenia and other severe platelet function disorders.
AB  - Patients with rare qualitative platelet disorders or platelet function disorders
      (PFDs) may present to the hospital physician with severe bleeding episodes or
      excessive surgical bleeding. Although standard treatment consists of platelet
      transfusions, repeated transfusions may result in the development of antiplatelet
      antibodies (APA) or clinical refractoriness, rendering further platelet therapy
      ineffective. In such settings, an approved treatment option for patients with
      Glanzmann's thrombasthenia (GT), one of the well-known rare PFDs, is recombinant
      activated coagulation factor VII (rFVIIa). Data regarding the efficacy of rFVIIa
      in patients with GT and platelet refractoriness are available from a large
      patient registry, an international survey, and multiple case reports and
      demonstrate efficacy in patients with and without refractoriness or APA. This
      article reviews the rFVIIa clinical data in patients with GT and platelet
      refractoriness and discusses clinical implications relevant to the hospital-based
      physician. Because uncontrolled bleeding can be life-threatening, hospital
      physicians should be alert to the signs of platelet refractoriness, be able to
      recognize continued internal or external bleeding, and know how to adapt
      treatment regimens for the effective management of bleeding. The management of
      patients who receive rFVIIa should occur in consultation with a hematologist with
      experience in PFDs, and patients with suspected platelet refractoriness should be
      referred to such a hematologist as early as possible. A critical unmet need is
      the development of a definition of an adequate response to platelet transfusion,
      which would facilitate early recognition of platelet refractoriness in patients
      with PFDs who exhibit a normal platelet count.

PMID- 28435310
TI  - Tropical diseases of the myocardium: a review.
AB  - Cardiovascular diseases are widely distributed throughout the world. Human
      parasitic infections are ubiquitous. Tropical parasites are increasingly
      recognized as causes of cardiovascular diseases. In this review, we address the
      most frequently reported parasites that directly infect the myocardium, including
      Trypanosoma cruzi, the protozoal causative agent of American trypanosomiasis
      (Chagas disease), and Taenia solium, the cestode causative agent of taeniasis and
      cysticercosis. We also discuss tropical endomyocardial fibrosis, trichinellosis
      and schistosomiasis. Health systems, attitudes, the perceptions of both patients
      and physicians as well as socioeconomic factors should all be explored and
      recognized as crucial factors for improving the control of cardiovascular
      diseases in the tropics. Clinicians throughout the world must remain aware of
      imported parasites as potential causes of cardiac diseases.

PMID- 28435311
TI  - Application of Bayesian decision-making to laboratory testing for Lyme disease
      and comparison with testing for HIV.
AB  - In this study, Bayes' theorem was used to determine the probability of a patient
      having Lyme disease (LD), given a positive test result obtained using commercial
      test kits in clinically diagnosed patients. In addition, an algorithm was
      developed to extend the theorem to the two-tier test methodology. Using a disease
      prevalence of 5%-75% in samples sent for testing by clinicians, evaluated with a
      C6 peptide enzyme-linked immunosorbent assay (ELISA), the probability of
      infection given a positive test ranged from 26.4% when the disease was present in
      5% of referrals to 95.3% when disease was present in 75%. When applied in the
      case of a C6 ELISA followed by a Western blot, the algorithm developed for the
      two-tier test demonstrated an improvement with the probability of disease given a
      positive test ranging between 67.2% and 96.6%. Using an algorithm to determine
      false-positive results, the C6 ELISA generated 73.6% false positives with 5%
      prevalence and 4.7% false positives with 75% prevalence. Corresponding data for a
      group of test kits used to diagnose HIV generated false-positive rates from 5.4%
      down to 0.1% indicating that the LD tests produce up to 46 times more false
      positives. False-negative test results can also influence patient treatment and
      outcomes. The probability of a false-negative test for LD with a single test for
      early-stage disease was high at 66.8%, increasing to 74.9% for two-tier testing.
      With the least sensitive HIV test used in the two-stage test, the false-negative
      rate was 1.3%, indicating that the LD test generates ~60 times as many false
      negative results. For late-stage LD, the two-tier test generated 16.7% false
      negatives compared with 0.095% false negatives generated by a two-step HIV test,
      which is over a 170-fold difference. Using clinically representative LD test
      sensitivities, the two-tier test generated over 500 times more false-negative
      results than two-stage HIV testing.

PMID- 28435312
TI  - Prevalence of chronic pain with neuropathic characteristics: a randomized
      telephone survey among medical center patients in Kuwait.
AB  - BACKGROUND: Chronic pain with neuropathic characteristics is considered to be an
      international health problem. However, surveys on the actual incidence of
      neuropathic pain have not been conducted in many Middle East countries, including
      Kuwait. The aim of this study was to examine the incidence of pain and medical
      comorbidities among a random sample of patients treated at a large medical center
      in Kuwait. METHODS: A list of 1,000 patients was created from the hospital
      medical record system, and a telephone survey was conducted on 759 patients who
      responded to the phone call, of which 67.2% (N=510) participated. Those who
      stated that they had pain every day for the past 3 months were invited to answer
      additional questions about their pain. RESULTS: Fifty-six percentage of those
      surveyed (N=283) reported experiencing chronic pain. Total average age was 49.2
      years (SD=14.5), 45.5% were female, and 70.5% were Kuwaiti nationals. Most
      (74.3%) reported having diabetes and one-third (32.2%) showed evidence of
      neuropathic pain characteristics (mean DN4=2.8, SD=1.7). Other comorbid medical
      conditions were prevalent (48.4% hypertension, 30.4% arthritis, 22.6% heart
      disease, and 20.4% asthma) with an average of 2.3 (SD=1.3) medical problems per
      person. Those with pain tended to be older, female, unemployed, and overweight
      (p<0.01). The pain was mostly located in the lower extremities and those with
      neuropathic pain tended to report a higher intensity of pain and a higher
      frequency of seeking treatment for their pain in a clinic or hospital (p<0.05).
      Most relied on over-the-counter medications for their pain (38.1%). Very few were
      taking prescription medication for their pain. CONCLUSION: This survey suggests
      that chronic pain is more prevalent in a medical population in Kuwait than
      previously anticipated. Health care services and behavioral interventions to
      improve lifestyle changes in Kuwait and other Arab countries are needed to
      positively impact pain and reduce other comorbidities.

PMID- 28435314
TI  - Factors affecting patients' comfort during fiberoptic bronchoscopy and
      endobronchial ultrasound.
AB  - OBJECTIVE: This study investigated the factors that can affect the comfort of
      patients who underwent diagnostic fiberoptic bronchoscopy (FOB) and diagnostic
      endobronchial ultrasonography (EBUS) for the first time and the effect of the
      patients' anxiety level on their comfort during the procedure. MATERIALS AND
      METHODS: We recorded the demographics of the patients, the medications they used
      previously, the anesthesia applied during the procedure, the experience of the
      operator, the insertion technique of the bronchoscope, the types of the
      bronchoscopic interventions during the procedure, the duration of the procedure,
      and the anxiety levels of the patients before the session. Patients' discomfort
      level before and after the procedure and anxiety levels before the procedure were
      evaluated using a visual analog scale (VAS), and willingness for repeating FOB
      and EBUS was assessed using a questionnaire. RESULTS: We found that longer
      examination time, higher anxiety level before the procedure, the nasal insertion
      of bronchoscope, and higher number of interventions are related to the increased
      discomfort during FOB and EBUS. Patients' willingness for repeating FOB and EBUS
      increased as the level of discomfort decreased during the procedure. CONCLUSION:
      The patient's anxiety level should be determined using a questionnaire before the
      FOB and EBUS procedures, and the operator should adjust their procedure according
      to the patients' anxiety level.

PMID- 28435315
TI  - Retrospective analyses versus RCTs: comparing like with like?

PMID- 28435316
TI  - Subanesthetic ketamine for pain management in hospitalized children, adolescents,
      and young adults: a single-center cohort study.
AB  - BACKGROUND: Subanesthetic doses of ketamine, an N-methyl-d-aspartate receptor
      antagonist used as an adjuvant to opioid for the treatment of pain in adults with
      acute and chronic pain, have been shown, in some instances, to improve pain
      intensity and to decrease opioid intake. However, less is known about the role of
      ketamine in pain management in children, adolescents, and young adults. PURPOSE:
      We examined the effects of subanesthetic ketamine on pain intensity and opioid
      intake in children, adolescents, and young adults with acute and chronic pain
      syndromes treated in an inpatient setting. METHODS: This is a longitudinal cohort
      study of patients treated with subanesthetic ketamine infusions in regular
      patient care units in a tertiary pediatric hospital. Primary outcomes included
      changes in pain scores and morphine-equivalent intake. RESULTS: The study cohort
      included 230 different patients who during 360 separate hospital admissions
      received subanesthetic ketamine infusions for pain management. Overall, ketamine
      infusions were associated with significant reductions in mean pain scores from
      baseline (mean pain scores 6.64 [95% CI: 6.38-6.90]) to those recorded on the day
      after discontinuation of ketamine (mean pain scores 4.38 [95% CI: 4.06-4.69]),
      p<0.001. Importantly, the effect of ketamine on pain scores varied according to
      clinical diagnosis (p=0.011), infusion duration (p=0.004), and pain location
      (p=0.004). Interestingly, greater reductions in pain scores were observed in
      patients with cancer pain and patients with pain associated with pancreatitis and
      Crohn's disease. There were no records of psychotomimetic side effects requiring
      therapy. CONCLUSION: These data suggest that administration of subanesthetic
      ketamine for pain management is feasible and safe in regular inpatient care units
      and may benefit children, adolescents, and young adults with acute and chronic
      pain. This study is informative and can be helpful in determining sample and
      effect sizes when planning clinical trials to determine the role of subanesthetic
      ketamine infusions for pain management in pediatric patients.

PMID- 28435317
TI  - Systemic alterations in plasma proteins from women with chronic widespread pain
      compared to healthy controls: a proteomic study.
AB  - Chronic widespread pain (CWP) is a complex pain condition that is difficult to
      treat. The prevalence of CWP approximates ~10% of the general population, with
      higher prevalence in women. Lack of understanding of molecular mechanisms has
      been a challenge for diagnosis and treatment of chronic pain. The aim of this
      study was to explore the systemic protein changes in CWP compared to those in
      healthy controls (CON). By applying 2-dimensional gel electrophoresis, we
      analyzed the protein pattern of plasma samples from women with CWP (n=16) and
      healthy women (n=23). The proteomic data were analyzed using multivariate
      statistical models, and altered proteins were identified using mass spectrometry.
      The proteome analysis was further validated by gel-free Western blot.
      Multivariate statistical data analysis of quantified proteins revealed 22 altered
      proteins in women with CWP, compared to CON group. Many of the identified
      proteins are previously known to be involved in different parts of the complement
      system and metabolic and inflammatory processes, e.g., complement factor B,
      vitamin D-binding protein, ceruloplasmin, transthyretin and alpha-2-HS
      glycoprotein. These results indicate that important systemic protein differences
      exist between women with CWP and healthy women. Further, this study illustrates
      the potential use of proteomics to detect biomarkers that may provide new
      insights into the molecular mechanism(s) of chronic pain. However, further larger
      investigations are required in order to confirm these findings before it will be
      possible to identify proteins as potential pain biomarkers for clinical use.

PMID- 28435318
TI  - Prevalence, characteristics, and burden of failed back surgery syndrome: the
      influence of various residual symptoms on patient satisfaction and quality of
      life as assessed by a nationwide Internet survey in Japan.
AB  - We conducted a cross-sectional, Internet-based survey with a nationally
      representative sample of Japanese adults to assess the prevalence and
      characteristics of failed back surgery syndrome (FBSS). Data regarding the
      residual symptoms and patient satisfaction from an online survey of 1842 lumbar
      surgery patients revealed the prevalence of FBSS to be 20.6% (95% confidence
      interval [CI], 18.8-22.6). The prevalence of low back pain, dull ache, numbness,
      cold sensations, and paresthesia after surgery was 94.0%, 71.1%, 69.8%, 43.3%,
      and 35.3%, respectively. With a logistic regression model, severe residual low
      back pain (numerical rating scale 8-10), higher pain intensity, and multiple low
      back surgeries were strongly associated with FBSS, with odds ratios of 15.21 (95%
      CI, 7.79-29.7), 1.40 (95% CI, 1.32-1.49), and 1.87 (95% CI, 1.25-2.81),
      respectively. Respondents with FBSS had significantly lower EuroQol-5D (P<0.001)
      values and significantly higher scores on the Kessler six-item psychological
      distress scale (P<0.001), compared with the non-FBSS group. Our findings indicate
      that residual sensations have a significant effect on patient quality of life,
      similar to that of chronic low back pain. Precise presurgical provision of
      prognoses based on comprehensive epidemiologic data, as well as scrupulous
      attention to patient satisfaction and clinical progress may help reduce the
      incidence of FBSS.

PMID- 28435319
TI  - Sex differences in fear of pain: item-level analysis of the Fear of Pain
      Questionnaire III.
AB  - OBJECTIVES: This study aimed to investigate sex differences in fear of pain (FOP)
      measured by the Fear of Pain Questionnaire III (FPQ-III) in a nonclinical sample.
      The FPQ-III is a self-report inventory measuring FOP, with 30 items, divided into
      three subscales: Severe, Minor and Medical Pain. METHODS: A total of 185 subjects
      participated (49.7% females) in this study. Sex differences on overall FOP, the
      subscales, and at item level were examined. One-way analysis of variance tested
      the association between sex and FOP, measured by overall FOP and the subscales.
      Ordinal regression analysis enabled item-level analysis of the FPQ-III and was
      conducted to explore further specificity of FOP in males compared to females.
      RESULTS: Overall FOP and fear of Severe Pain was significantly higher in females
      than in males, as measured by the FPQ-Total and the FPQ-Severe. Moreover, females
      were more likely to report higher FOP than males on 16 items (p<0.05). Further
      inspection revealed that females scored significantly higher than males on all
      items on the Severe Pain subscale. When controlling for multiple comparisons six
      items reached significance (p<0.001). Five of these items belonged to the
      subscale Severe Pain. When controlling for overall FOP one item, also from the
      Severe Pain subscale, reached significance (p<0.001). CONCLUSION: There are sex
      differences in severe FOP, with higher FOP in females compared to males.
      Potential explanations are sex differences in the 1) psychosocial mechanisms of
      fear and anxiety, and 2) emotional reactions to and interpretation of FPQ-III
      Severe Pain items.

PMID- 28435313
TI  - Evidence and consensus recommendations for the pharmacological management of pain
      in India.
AB  - Despite enormous progress in the field of pain management over the recent years,
      pain continues to be a highly prevalent medical condition worldwide. In the
      developing countries, pain is often an undertreated and neglected aspect of
      treatment. Awareness issues and several misconceptions associated with the use of
      analgesics, fear of adverse events - particularly with opioids and surgical
      methods of analgesia - are major factors contributing to suboptimal treatment of
      pain. Untreated pain, as a consequence, is associated with disability, loss of
      income, unemployment and considerable mortality; besides contributing majorly to
      the economic burden on the society and the health care system in general.
      Available guidelines suggest that a strategic treatment approach may be helpful
      for physicians in managing pain in real-world settings. The aim of this
      manuscript is to propose treatment recommendations for the management of
      different types of pain, based on the available evidence. Evidence search was
      performed by using MEDLINE (by PubMed) and Cochrane databases. The types of
      articles included in this review were based on randomized control studies, case
      control or cohort studies, prospective and retrospective studies, systematic
      reviews, meta-analyses, clinical practice guidelines and evidence-based consensus
      recommendations. Articles were reviewed by a multidisciplinary expert panel and
      recommendations were developed. A stepwise treatment algorithm-based approach
      based on a careful diagnosis and evaluation of the underlying disease, associated
      comorbidities and type/duration of pain is proposed to assist general
      practitioners, physicians and pain specialists in clinical decision making.

PMID- 28435320
TI  - Identification, prevalence, and treatment of painful diabetic neuropathy in
      patients from a rural area in South Carolina.
AB  - Diabetic peripheral neuropathy (DPN) represents significant burdens to many
      patients and the public health-care system. Patients with diabetes in rural areas
      have higher risk of developing complications and having less access to proper
      treatment. We studied a rural population of patients with diabetes who attended a
      pharmacist-led free clinic for a diabetic education program. Our objectives were
      to 1) determine the prevalence of DPN and painful diabetic neuropathy (p-DN) in
      patients with type 2 diabetes; 2) assess the proportion of patients with DPN and
      p-DN left undocumented upon physician referral to a pharmacist-led free clinic;
      and 3) determine the appropriateness of pain medication regimen. We performed a
      retrospective analysis of clinical records of patients from the Presbyterian
      College School of Pharmacy (PCSP) Wellness Center located in Clinton, SC.
      Diagnoses of DPN and/or p-DN were obtained from referral notes in the clinical
      records and compared with results from foot examinations performed in the free
      clinic and clinical features. Medication regimens were also obtained and compared
      using American Academy of Neurology (AAN) treatment guidelines. Within our study
      population (n=111), the prevalence of DPN was 62.2% (national average of 28%-45%)
      and that of p-DN was 23.4% (national average of 11%-24%). In p-DN patients
      (n=26), 53.8% (n=14) had a documented diagnosis of p-DN by the referring
      physician, and 46.2% (n=12) were identified by the pharmacists. A total of 95%
      (19 of 20) of the patients treated for p-DN received adequate pharmacological
      agents, though suboptimal as per clinical guidelines. More than 50% of the
      patients used subtherapeutic doses of their medications. Gabapentin was the most
      frequently used medication in our population (65.4%). Patients in rural South
      Carolina had a higher prevalence of DPN and p-DN with >60% undocumented cases of
      p-DN. More than 95% of treated patients did not receive optimum therapy according
      to AAN guidelines.

PMID- 28435321
TI  - A behavioral medicine intervention for community-dwelling older adults with
      chronic musculoskeletal pain: protocol for a randomized controlled trial.
AB  - BACKGROUND: Chronic musculoskeletal pain is a major health problem among older
      adults, particularly those who live alone and/or those who are dependent on
      formal care. Chronic pain is associated with mobility problems, falls, fear of
      falling, catastrophizing thoughts, and a lower quality of life. Research shows
      that physical therapy interventions based on behavioral medicine approaches are
      beneficial for middle-aged adults with chronic pain. However, there appears to be
      no previous randomized controlled trials (RCTs) based on this theoretical
      framework that have examined the effect on older adults with chronic
      musculoskeletal pain who live alone at home and are dependent on formal care to
      manage their everyday lives. The aim of the planned study is to evaluate the
      effect of an individually tailored integrated physical therapy intervention based
      on a behavioral medicine approach compared with the effect of standard care.
      METHODS/DESIGN: The planned study is an RCT that will include one intervention
      and one control group involving a total of 150 adults aged >=75 years with
      chronic musculoskeletal pain who live alone at home and are dependent on formal
      care to manage their everyday lives. The intervention will involve a 12-week home
      based individually tailored intervention that will be designed to enhance the
      participants' ability to perform everyday activities by improving physical
      function and reducing pain-related disability and beliefs. The control group will
      be given standard care, including general advice about physical activity. The
      participants will be assessed at baseline and at 3 and 6 months after baseline.
      The primary outcome will be pain-related disability and physical performance.
      DISCUSSION: The intervention, if effective, will have the potential to be the
      basis of the first evidence-based guidelines for physical therapists who work
      with older adults with chronic musculoskeletal pain.

PMID- 28435322
TI  - Spinal anesthesia after intraoperative cardiac arrest during general anesthesia
      in an infant.
AB  - Although generally safe and effective, severe perioperative complications,
      including cardiac arrest, may occur during general anesthesia in infants. With
      the emergence of evidence that specific anesthetic agents may affect future
      neurocognitive outcomes, there has been an increased focus on alternatives to
      general anesthesia, including spinal anesthesia. We present a case of cardiac
      arrest during general anesthesia in an infant who required urologic surgery.
      During the subsequent anesthetic care, spinal anesthesia was offered as an
      alternative to general anesthesia. The risks of severe perioperative
      complications during general anesthesia are reviewed, etiologic factors for such
      events are presented, and the use of spinal anesthesia as an alternative to
      general anesthesia is discussed.

PMID- 28435323
TI  - Ambulatory thyroidectomy: an anesthesiologist's perspective.
AB  - Thyroidectomy has been performed on an inpatient basis because of concerns
      regarding postoperative complications. These include cervical hematoma, bilateral
      recurrent laryngeal nerve injury and symptomatic hypocalcemia. We have reviewed
      the current available evidence and aimed to collate published data to generate
      incidence of the important complications. We performed a literature search of
      Medline, EMBASE and the Cochrane database of randomized trials. One hundred sixty
      papers were included. Twenty-one papers fulfilled inclusion criteria. Thirty
      thousand four hundred fifty-three day-case thyroid procedures were included. Ten
      papers were prospective and 11 retrospective. The incidences of complications
      were permanent vocal cord paralysis 7/30259 (0.02%), temporary hypocalcemia
      129/4444 (2.9%), permanent hypocalcemia 405/29203 (1.39%), cervical hematoma
      145/30288 (0.48%) and readmission rate 105/29609 (0.35%). Analysis of cervical
      hematoma data demonstrated that in only 3/14 cases the hematoma presented as an
      inpatient, and in the remaining 11/14, it occurred late, with a range of 2-9
      days. There is a paucity of data relating to anesthetic techniques associated
      with ambulatory thyroidectomy. Cost comparison between outpatient and inpatient
      thyroidectomy was reported in three papers. Cost difference ranged from $676 to
      $2474 with a mean saving of $1301 with ambulatory thyroidectomy. There is a body
      of evidence that suggests that ambulatory thyroidectomy in the hands of
      experienced operating teams within an appropriate setting can be performed with
      acceptable risk profile. In most circumstances, this will be limited to
      hemithyroidectomies to reduce or avoid the potential for additional morbidity. We
      have found little evidence to support the use of one anesthetic technique over
      another. The rates of hospital admission and readmission related to anesthetic
      factors appear to be low and predominantly related to pain and postoperative
      nausea and vomiting. A balanced anesthetic technique incorporating appropriate
      analgesic and antiemetic regimens is essential to avoid unnecessary hospital
      admission/readmission.

PMID- 28435324
TI  - Symptomatic central nervous system involvement in adult patients with acute
      myeloid leukemia.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) rarely involves the central nervous
      system (CNS). Little is known about the clinical course in adult AML patients
      since most studies examined pediatric patients. Therefore, this study analyzed
      the data of patients treated in three prospective trials of the "Study Alliance
      Leukemia" (SAL) study group for CNS involvement. METHODS: In all, 3,261 AML
      patients included in the prospective AML96, AML2003, and AML60+ trials of the SAL
      study group were analyzed. Symptomatic patients underwent cerebrospinal fluid
      (CSF) puncture and CNS involvement was diagnosed depending on morphology and/or
      flow cytometry of the CSF. Cytogenetic, molecular, clinical, and laboratory
      parameters were analyzed in order to identify risk factors. RESULTS: A total of
      55 patients had proven symptomatic CNS involvement. Significantly more patients
      revealed CNS involvement at relapse (34 patients, 2.9%) compared with first
      diagnosis (21 patients, 0.6%), p<0.001. CNS involvement at initial diagnosis had
      a significantly higher frequency in patients with complex aberrant karyotypes,
      high serum lactate dehydrogenase activity, French-American-British M5 subtype,
      FLT3-internal tandem duplication (ITD) mutations alone, and co-occurrence of a
      FLT3-ITD and NPM1 mutation. Furthermore, AML patients with CNS involvement at
      diagnosis had an inferior outcome compared with patients without CNS involvement
      even if treated with intrathecal chemotherapy with an overall survival of 11%
      versus 30% at 5 years, p=0.004. CONCLUSION: This study analyzed the largest data
      set of adult AML patients with proven CNS involvement reported so far. The data
      demonstrated very low prevalence of CNS involvement at initial diagnosis in adult
      patients with AML, and described new risk factors. In patients with risk factors,
      intense diagnostic and treatment strategies should be employed in the future.

PMID- 28435325
TI  - The clinical development of obinutuzumab for the treatment of follicular
      lymphoma.
AB  - Impressive progress has been made in recent decades for advanced-stage follicular
      lymphoma with the availability of anti-CD20 monoclonal antibodies, initially
      rituximab and more recently obinutuzumab. Obinutuzumab is a unique, third
      generation, fully humanized glycoengineered IgG1 type II anti-CD20 monoclonal
      antibody. It has been shown to have increased antitumor activity compared to
      rituximab in preclinical studies, including whole-blood B-cell depletion assays,
      xenograft models, and primate models. This has spurred on the development of
      obinutuzumab through Phase I/II trials as monotherapy and in combination with
      chemotherapeutic agents and other targeted therapies. Its efficacy compared to
      rituximab and in rituximab-refractory disease has led to its continued
      development and eventual approval for the treatment of follicular lymphoma. Here
      in this review, we highlight the design and development of obinutuzumab in the
      treatment of advanced stage grade 1-3A follicular lymphoma and its future
      directions.

PMID- 28435326
TI  - The association between thyroid disorders and incident gout: population-based
      case-control study.
AB  - CONTEXT: Thyroid hormones influence kidney function and thereby might alter serum
      urate levels, a major risk factor for gouty arthritis. OBJECTIVE: To assess the
      risk of developing incident gout in association with hypothyroidism or
      hyperthyroidism. DESIGN: Retrospective population-based case-control analysis.
      SETTING: UK-based Clinical Practice Research Datalink, a primary care research
      database. PATIENTS: We identified adult patients with a diagnosis of incident
      gout between 1990 and 2014. We matched one control to each gout case in terms of
      age, sex, general practice, calendar time, and years of active history in the
      database. MAIN OUTCOME MEASURE: We used conditional logistic regression to
      calculate odds ratios (ORs) with 95% confidence intervals (CIs) for developing
      gout in association with hypo- or hyperthyroidism and adjusted for potential
      confounders. RESULTS: The study population encompassed 68,159 incident gout
      cases, of whom 78.8% were male, and the same number of matched controls. There
      was no increased risk of gout in patients with hypothyroidism: adjusted OR of
      gout of 1.12 (95% CI 1.05-1.20) compared with no hypothyroidism. Current short
      term treatment of thyroid hormone replacement therapy was associated with an
      adjusted OR of gout of 1.54 (95% CI 1.24-1.92), compared with no treatment.
      Neither hyperthyroidism nor current treatment with thyroid suppression therapy
      was associated with gout (adjusted OR, 1.08 [95% CI 0.95-1.22] and 0.82 [95% CI
      0.57-1.17], respectively). CONCLUSION: This large observational study does not
      provide evidence that hypothyroidism or hyperthyroidism, irrespective of
      treatment, is associated with a clinically relevant increased risk of developing
      incident gout. There may be an exception among patients with newly diagnosed and
      treated hypothyroidism.

PMID- 28435327
TI  - Effect of menopause on hormonal receptors in ampullae of the fallopian tube with
      a special reference to the p53 signature.
AB  - OBJECTIVES: Age-related changes in the expression of hormonal receptors have not
      been well examined in the fallopian tube (FT). We herein report the effect of
      menopause on the hormone receptors in ampullae of the FTs (AFTs), in comparison
      with cortical inclusion cysts (CICs) of the ovary. METHODS: A total of 84 AFTs
      and 16 fimbriae of FTs, which were obtained from 26 premenopausal and 58
      postmenopausal women; and 27 postmenopausal CICs were immunohistochemically
      studied for the expression of p53, Ki-67, estrogen receptor-alpha (ER-alpha), and
      progesterone receptor A (PRA). Apoptotic cells were identified using a TUNEL
      assay. RESULTS: Postmenopausal AFTs showed a significantly lower labeling index
      (LI) for Ki-67 (P<0.001), apoptosis (P=0.03), and PRA (P<0.001) than
      premenopausal AFTs. No significant correlation with immunohistochemical markers
      was found in premenopausal AFTs, but the LI for PRA was positively correlated
      with that for Ki-67 (P=0.004) and inversely with that for p53 (P=0.023) in
      postmenopausal AFTs. The expression of immunohistochemical markers was closely
      correlated between ampullae and fimbriae of the FT. The p53 signature (p53S) was
      detected in five postmenopausal AFTs (mean age: 70.2 years) and was not detected
      in any CICs. The immunohistochemical profile of p53S was low expression of Ki-67,
      apoptosis, and PRA, and high expression of ER-alpha. The expression of PRA in
      CICs was significantly higher than that in AFTs (P=0.001). CONCLUSION: The
      expression of PRA was significantly lower in postmenopausal AFTs than in
      premenopausal AFTs, whereas the expression of PRA was well preserved in
      postmenopausal CICs.

PMID- 28435328
TI  - Aortic valve papillary fibroelastoma causing embolic strokes: a case report and
      review.
AB  - Papillary fibroelastomas (PFEs) are the second most common benign neoplasms of
      the cardiac valves and are being recognized more frequently because of higher
      resolution imaging technology. PFEs are associated with substantial complications
      that are secondary to systemic embolism. Surgical resection should be offered to
      all patients who have symptoms and to asymptomatic patients who have pedunculated
      lesions or tumors larger than 1 cm in diameter. Herein, we present a patient who
      presented for a second time in 2 months with stroke symptoms. During his first
      admission, a transthoracic echocardiogram was performed and he was sent home
      after resolution of his symptoms and a grossly negative workup. During his second
      admission, a transesophageal echocardiogram was performed and the PFE was found
      and later excised. While this discussion reviews the literature with regard to
      detection and management, it will hopefully serve as a reminder to keep this on
      the differential when the workup has remained without an obvious source.

PMID- 28435329
TI  - The first 8 years: International Medical Case Reports Journal - summary of
      publications from 2008 to July 2016.

PMID- 28435330
TI  - First case of imported chikungunya infection in Croatia, 2016.
AB  - In recent years, several European countries reported cases of imported
      chikungunya infection. We present the first imported clinically manifested
      chikungunya fever in Croatia. A 27-year-old woman returned to Croatia on 21 March
      2016, after she stayed in Costa Rica for two months where she had noticed a
      mosquito bite on her left forearm. Five days after the mosquito bite she
      developed severe arthralgias, fever and erythematous papular rash. In next few
      days symptoms gradually subsided. After ten days she felt better, but arthralgias
      re-appeared accompanied with morning stiffness. Two weeks after the onset of the
      disease she visited the infectious diseases outpatient department. The physical
      examination revealed rash on the trunk, extremities, palms and soles. Laboratory
      findings showed slightly elevated liver transaminases. Serological tests
      performed on day 20 after disease onset showed a high titer of chikungunya virus
      (CHIKV) IgM and IgG antibodies which indicated CHIKV infection. CHIKV-RNA was not
      detected. Serology to dengue and Zika virus was negative. The patient was treated
      with nonsteroid anti-inflammatory drugs and paracetamol. Her symptoms
      ameliorated, however, three months later she still complaint of arthralgias. The
      presented case highlights the need for inclusion of CHIKV in the differential
      diagnosis of arthralgia in all travelers returning from countries with documented
      CHIKV transmission.

PMID- 28435331
TI  - Pulmonary alveolar hemorrhage following thrombolytic therapy.
AB  - We report a case of a 58-year-old male without any comorbidities who was
      thrombolysed with streptokinase for acute anterior wall myocardial infarction and
      developed massive hemoptysis with dyspnea and imaging features showing bilateral
      alveolar infiltrates. He was diagnosed with pulmonary alveolar hemorrhage and
      treated conservatively. His condition improved, and follow-up imaging showed
      resolution. Alveolar hemorrhage is a rare and life-threatening complication of
      thrombolytic therapy.

PMID- 28435332
TI  - Lacquer cracks observed in peripheral fundus of eyes with high myopia.
AB  - We report a case with lacquer cracks observed in the peripheral fundus. A 37-year
      old patient with bilateral high myopia who visited our clinic was examined by
      fluorescein angiography (FA) and fundus autofluorescence (FAF) to determine
      whether there were myopic fundus lesions. FA showed many arch-shaped,
      hyperfluorescent linear lesions running circumferentially in the peripheral
      fundus. FAF showed hypo-autofluorescence at the corresponding sites. These
      characteristics were very similar to the lacquer cracks present in the posterior
      fundus in highly myopic eyes. Although lacquer cracks in the peripheral fundus
      are rare, they should be considered in the differential diagnosis of peripheral
      linear lesions showing hyperfluorescence in FA.

PMID- 28435334
TI  - Bispectral index value correlates with Glasgow Coma Scale in traumatic brain
      injury patients.
AB  - BACKGROUND: Accuracy of consciousness level assessment is very important. It may
      determine and influence further clinical decisions, thus influences patients'
      outcomes. The widest method in determining the level of awareness is the Glasgow
      Coma Scale (GCS). Despite its common use, GCS scores obtained by one clinician
      may differ from others depending on their interpretations and past experience.
      One of the tools used to assess the level of consciousness objectively is
      bispectral index (BIS). The aim of this study was to identify the correlation
      between BIS and GCS score in patients with traumatic brain injury. PATIENTS AND
      METHODS: A total of 78 patients who were admitted to emergency room for traumatic
      brain injury were included in this study. One observer evaluated the GCS of all
      patients to minimize subjectivity. Another investigator then obtained the BIS
      values for each patient. Spear-man's rank correlation coefficient was used to
      determine whether GCS correlated with BIS value. RESULTS: In 78 patients, the BIS
      was found to be significantly correlated with GCS (r=0.744, p<0.01). The BIS
      values increased with an increasing GCS. Mean BIS values of mild, moderate, and
      severe head injury were 88.1+/-5.6, 72.1+/-11.1, and 60.4+/-11.7, respectively.
      CONCLUSION: In this study, a significant correlation existed between GCS and BIS.
      This finding suggests that BIS may be used for assessing GCS in patients with
      traumatic brain injury. However, the scatters of BIS values for any GCS level may
      limit the BIS in predicting GCS accurately.

PMID- 28435335
TI  - What is the effect of a shoulder-strengthening program to prevent shoulder pain
      among junior female team handball players?
AB  - BACKGROUND: Excessively high stresses are applied to the shoulder joint of
      handball players, mainly caused by overhead throwing. Shoulder pain is a
      significant problem among junior female team handball players and both male and
      female top-level team handball players in Norway. METHOD: A randomized selection
      was performed among the best female junior teams (J 16) in the Trondelag region
      of Norway in the 2014-2015 season. Three teams were randomized to the
      intervention group and three teams to the control group. Players in the
      intervention group (n=53) participated in a seven-month, three-times-a-week
      shoulder-muscle strength-training program, while those in the control group
      (n=53) participated in a comparable handball training, but did not conduct any
      specific strength training during the season. RESULTS: A strength-training
      program had no effect on the prevention of shoulder pain. Overall, the players
      reported shoulder pain, but graded the pain low on visual analog scale (VAS).
      Both the intervention group and the control group reported pain under 1 on VAS at
      baseline and posttest, and there was no significant difference within or between
      the groups when it came to the intensity of pain reported on VAS. A significant
      difference (p<0.048) was found between the groups on the sport-specific part of
      the quick-Disability of the Arm, Shoulder and Hand (DASH) form, but it did not
      fulfill the minimal demand to change and the players scored it low, something
      that indicates little functional problems when it comes to team handball. The
      intervention group was significantly stronger (p<0.008) on the push-ups test
      compared to the control group on the posttest. The intervention group increased
      the number of push-ups from 3.1 to 6.4, while the control group went from 2.3 to
      3.6. Aside from this, there were no significant differences in between the
      groups. CONCLUSION: A shoulder-strengthening program had no effect on the
      prevention of shoulder pain among junior female team handball players.

PMID- 28435333
TI  - New insights into therapeutic activity and anticancer properties of curcumin.
AB  - Natural compounds obtained from plants are capable of garnering considerable
      attention from the scientific community, primarily due to their ability to check
      and prevent the onset and progress of cancer. These natural compounds are
      primarily used due to their nontoxic nature and the fewer side effects they cause
      compared to chemotherapeutic drugs. Furthermore, such natural products perform
      even better when given as an adjuvant along with traditional chemotherapeutic
      drugs, thereby enhancing the potential of chemotherapeutics and simultaneously
      reducing their undesired side effects. Curcumin, a naturally occurring polyphenol
      compound found in the plant Curcuma longa, is used as an Indian spice. It
      regulates not only the various pathways of the immune system, cell cycle
      checkpoints, apoptosis, and antioxidant response but also numerous intracellular
      targets, including pathways and protein molecules controlling tumor progression.
      Many recent studies conducted by major research groups around the globe suggest
      the use of curcumin as a chemopreventive adjuvant molecule to maximize and
      minimize the desired effects and side effects of chemotherapeutic drugs. However,
      low bioavailability of a curcumin molecule is the primary challenge encountered
      in adjuvant therapy. This review explores different therapeutic interactions of
      curcumin along with its targeted pathways and molecules that are involved in the
      regulation of onset and progression of different types of cancers, cancer
      treatment, and the strategies to overcome bioavailability issues and new targets
      of curcumin in the ever-growing field of cancer.

PMID- 28435336
TI  - Anterior cruciate ligament injury/reinjury in alpine ski racing: a narrative
      review.
AB  - The purpose of the present review was to: 1) provide an overview of the current
      understanding on the epidemiology, etiology, risk factors, and prevention methods
      for anterior cruciate ligament (ACL) injury in alpine ski racing; and 2) provide
      an overview of what is known pertaining to ACL reinjury and return to sport after
      ACL injury in alpine ski racing. Given that most of the scientific studies on ACL
      injuries in alpine ski racing have been descriptive, and that very few studies
      contributed higher level scientific evidence, a nonsystematic narrative review
      was employed. Three scholarly databases were searched for articles on ACL injury
      or knee injury in alpine ski racing. Studies were classified according to their
      relevance in relation to epidemiology, etiology, risk factors, and return to
      sport/reinjury prevention. Alpine ski racers (skiers) were found to be at high
      risk for knee injuries, and ACL tears were the most frequent diagnosis. Three
      primary ACL injury mechanism were identified that involved tibial internal
      rotation and anteriorly directed shear forces from ski equipment and the
      environment. While trunk muscle strength imbalance and genetics were found to be
      predictive of ACL injuries in development-level skiers, there was limited
      scientific data on ACL injury risk factors among elite skiers. Based on expert
      opinion, research on injury risk factors should focus on equipment design, course
      settings/speed, and athlete factors (eg, fitness). While skiers seem to make a
      successful recovery following ACL injury, there may be persistent neuromuscular
      deficits. Future research efforts should be directed toward prospective studies
      on ACL injury/reinjury prevention in both male and female skiers and toward the
      effects of knee injury on long-term health outcomes, such as the early
      development of osteoarthritis. International collaborations may be necessary to
      generate sufficient statistical power for ACL injury/reinjury prevention research
      in alpine ski racing.

PMID- 28435337
TI  - Treatment strategies for the female athlete triad in the adolescent athlete:
      current perspectives.
AB  - Since the passage of Title IX in 1972, female sports participation has
      dramatically increased. The benefits of physical activity, including decreased
      risk for heart disease and diabetes as well as improved body image and self
      esteem, far outweigh the risks. However, a select population of adolescent and
      young adult females may experience symptoms related to the female athlete triad
      (Triad), which refers to the interrelatedness of energy availability, menstrual
      function, and bone mineral density (BMD). These conditions often manifest
      clinically as disordered eating behaviors, menstrual irregularity, and stress
      fractures; an individual may suffer from 1 or all of the Triad components
      simultaneously. Because of the complex nature of the Triad, treatment is
      challenging and requires a multidisciplinary approach. Team members often include
      a physician, psychologist or psychiatrist, nutritionist or dietitian, physical
      therapist, athletic trainer, coach, family members, and most importantly, the
      patient. A thorough physical examination by a primary care physician is essential
      to identify all organs/systems that may be impacted by Triad-related conditions.
      Laboratory tests, assessment of bone density, nutritional assessment, and
      behavior health evaluation guide the management of the female athlete with Triad
      related conditions. Treatment of the Triad includes adequate caloric consumption
      to restore a positive energy balance; this is often the first step in successful
      management of the Triad. In addition, determining the cause of menstrual
      dysfunction (MD) and resumption of menses is very important. Nonpharmacologic
      interventions are the first choice; pharmacologic treatment for MD is reserved
      only for those patients with symptoms of estrogen deficiency or infertility.
      Lastly, adequate intake of calcium and vitamin D is critical for lifelong bone
      health. For this review, a comprehensive search of relevant databases from the
      earliest dates to July 2016 was performed. Keywords, including female athlete
      triad, adolescent female athlete, disordered eating, eating disorder, low energy
      availability, relative energy deficit, anorexia, bulimia, menstrual dysfunction,
      amenorrhea, oligoamenorrhea, bone mineral density, osteopenia, osteoporosis,
      stress fracture, and stress reaction, were utilized to search for relevant
      articles. Articles that directly addressed assessment and management of any 1 or
      all of the Triad components were included in this comprehensive review. The
      purpose of this narrative review is to provide the reader with the latest terms
      used to define the components of the female athlete triad, to discuss examination
      and diagnosis of the Triad, and lastly, to provide the reader with the latest
      evidence to successfully implement a multidisciplinary treatment approach when
      providing care for the adolescent female athlete who may be suffering from Triad
      related components.

PMID- 28435339
TI  - Compulsive exercise: links, risks and challenges faced.
AB  - Compulsive exercise is a condition described since 1970s. It is characterized by
      a craving for physical training, resulting in uncontrollable excessive exercise
      behavior with harmful consequences, such as injuries and impaired social
      relations. It has not been accepted as a mental disorder in either International
      Classification of Diseases or Diagnostic and Statistical Manual of Mental
      Disorders. The aim of this literature review was to critically examine the
      research on links (comorbidity), risks (negative consequences), and challenges
      faced (problems in a treatment context). This review found that compulsive
      exercise is associated with eating disorder pathology, perfectionism,
      neuroticism, narcissism, and obsessive compulsive traits. The most prominent
      negative consequences were injuries, social impairment, and depression, but more
      research is needed to uncover the potential dysfunction resulting from compulsive
      exercise. As the condition is not recognized as a psychiatric disorder, studies
      on treatment interventions are sparse. Problems with compliance have been
      reported; therefore, motivational interviewing has been proposed as a treatment
      approach, in combination with cognitive behavioral therapy. This review
      summarizes and discusses findings on links/comorbidity, risks/negative
      consequences, and treatment challenges. We suggest that future studies should pay
      attention to both prevention and counseling in sports settings, where compulsive
      exercise appears, as the condition may be associated with harmful consequences.

PMID- 28435338
TI  - Recommendations for optimizing methotrexate treatment for patients with
      rheumatoid arthritis.
AB  - Methotrexate (MTX) remains the cornerstone therapy for patients with rheumatoid
      arthritis (RA), with well-established safety and efficacy profiles and support in
      international guidelines. Clinical and radiologic results indicate benefits of
      MTX monotherapy and combination with other agents, yet patients may not receive
      optimal dosing, duration, or route of administration to maximize their response
      to this drug. This review highlights best practices for MTX use in RA patients.
      First, to improve the response to oral MTX, a high initial dose should be
      administered followed by rapid titration. Importantly, this approach does not
      appear to compromise safety or tolerability for patients. Treatment with oral
      MTX, with appropriate dose titration, then should be continued for at least 6
      months (as long as the patient experiences some response to treatment within 3
      months) to achieve an accurate assessment of treatment efficacy. If oral MTX
      treatment fails due to intolerability or inadequate response, the patient may be
      "rescued" by switching to subcutaneous delivery of MTX. Consideration should also
      be given to starting with subcutaneous MTX given its favorable bioavailability
      and pharmacodynamic profile over oral delivery. Either initiation of subcutaneous
      MTX therapy or switching from oral to subcutaneous administration improves
      persistence with treatment. Upon transition from oral to subcutaneous delivery,
      MTX dosage should be maintained, rather than increased, and titration should be
      performed as needed. Similarly, if another RA treatment is necessary to control
      the disease, the MTX dosage and route of administration should be maintained,
      with titration as needed.

PMID- 28435340
TI  - Stress and its predictors in pregnant women: a study in Saudi Arabia.
AB  - BACKGROUND: Although stress during pregnancy has negative effects on children's
      development and pregnant women's health, no study has assessed stress and its
      predictors among pregnant Saudi women. The aim of this study was to assess stress
      and identify its predictors in a sample of pregnant Saudi women. METHODS: A
      correlational study was carried out at King Abdulaziz Medical City in Riyadh,
      Kingdom of Saudi Arabia, on 438 pregnant women who attended the
      obstetrics/gynecology clinic. We collected data on their sociodemographic and
      oral health status. Stress was assessed using the Perceived Stress Scale (PSS).
      RESULTS: The sample mean age was 30.6+/-5.4 years, and 33.4% of the sample
      reported high stress levels (PSS >=20). The study revealed significantly high
      stress levels in women with no or low income, chronic disease, sleep deprivation,
      no teeth brushing, irregular eating patterns, gestational diabetes, and no family
      support (P<0.05). Self-reported oral health problems were significantly
      associated with high stress levels (P<0.05). A multiple linear regression model
      showed that no teeth brushing, chronic disease, sleep deprivation, gestational
      diabetes, and gingival redness predicted an increase in stress by a score of 3.6,
      2.4, 2.1, 1.4, and 1.4, respectively. CONCLUSION: It was estimated that three in
      ten pregnant women in King Abdulaziz Medical City reported high stress levels.
      Our study shed light on the relationship between healthy habits, oral health
      status, and perceived stress in pregnant women. This research may help health
      care practitioners who provide care to pregnant women, to educate them in regard
      to healthy habits, and to develop a program to reduce stress.

PMID- 28435341
TI  - Empowering patients of a mental rehabilitation center in a low-resource context:
      a Moroccan experience as a case study.
AB  - Mental, neurological and substance use (MNS) disorders represent a major source
      of disability and premature mortality worldwide. However, in developing countries
      patients with MNS disorders are often poorly managed and treated, particularly in
      marginalized, impoverished areas where the mental health gap and the treatment
      gap can reach 90%. Efforts should be made in promoting help by making mental
      health care more accessible. In this article, we address the challenges that
      psychological and psychiatric services have to face in a low-resource context,
      taking our experience at a Moroccan rehabilitation center as a case study. A
      sample of 60 patients were interviewed using a semi-structured questionnaire
      during the period of 2014-2015. The questionnaire investigated the reactions and
      feelings of the patients to the rehabilitation program, and their perceived
      psychological status and mental improvement, if any. Interviews were then
      transcribed and processed using ATLAS.ti V.7.0 qualitative analysis software.
      Frequencies and co-occurrence analyses were carried out. Despite approximately 30
      million inhabitants within the working age group, Morocco suffers from a shortage
      of specialized health workers. Our ethnographic observations show that
      psychiatric treatment can be ensured, notwithstanding these hurdles, if a public
      health perspective is assumed. In resource-limited settings, working in the field
      of mental health means putting oneself on the line, exposing oneself to new
      experiences, and reorganizing one's own skills and expertise. In the present
      article, we have used our clinical experience at a rehabilitation center in Fes
      as a case study and we have shown how to use peer therapy to overcome the
      drawbacks that we are encountered daily in a setting of limited resources.

PMID- 28435343
TI  - London Measure of Unplanned Pregnancy: guidance for its use as an outcome
      measure.
AB  - BACKGROUND: The London Measure of Unplanned Pregnancy (LMUP) is a
      psychometrically validated measure of the degree of intention of a current or
      recent pregnancy. The LMUP is increasingly being used worldwide, and can be used
      to evaluate family planning or preconception care programs. However, beyond
      recommending the use of the full LMUP scale, there is no published guidance on
      how to use the LMUP as an outcome measure. Ordinal logistic regression has been
      recommended informally, but studies published to date have all used binary
      logistic regression and dichotomized the scale at different cut points. There is
      thus a need for evidence-based guidance to provide a standardized methodology for
      multivariate analysis and to enable comparison of results. This paper makes
      recommendations for the regression method for analysis of the LMUP as an outcome
      measure. MATERIALS AND METHODS: Data collected from 4,244 pregnant women in
      Malawi were used to compare five regression methods: linear, logistic with two
      cut points, and ordinal logistic with either the full or grouped LMUP score. The
      recommendations were then tested on the original UK LMUP data. RESULTS: There
      were small but no important differences in the findings across the regression
      models. Logistic regression resulted in the largest loss of information, and
      assumptions were violated for the linear and ordinal logistic regression.
      Consequently, robust standard errors were used for linear regression and a
      partial proportional odds ordinal logistic regression model attempted. The latter
      could only be fitted for grouped LMUP score. CONCLUSION: We recommend the linear
      regression model with robust standard errors to make full use of the LMUP score
      when analyzed as an outcome measure. Ordinal logistic regression could be
      considered, but a partial proportional odds model with grouped LMUP score may be
      required. Logistic regression is the least-favored option, due to the loss of
      information. For logistic regression, the cut point for un/planned pregnancy
      should be between nine and ten. These recommendations will standardize the
      analysis of LMUP data and enhance comparability of results across studies.

PMID- 28435342
TI  - Patient web portals, disease management, and primary prevention.
AB  - BACKGROUND: Efforts aimed at health care reform and continued advances in
      information technologies have prompted interest among providers and researchers
      in patient web portals. Patient web portals are password-protected online
      websites that offer the patients 24-hour access to personal health information
      from anywhere with an Internet connection. METHODS: This article, which is based
      upon bibliographic searches in PubMed, reviews important developments in web
      portals for primary and secondary disease prevention, including patient web
      portals tethered to electronic medical records, disease-specific portals, health
      disparities, and health-related community web portals. RESULTS: Although findings
      have not been uniformly positive, several studies of the effectiveness of health
      care system patient portals in chronic disease management have shown promising
      results with regard to patient outcomes. Patient web portals have also shown
      promising results in increasing adherence with screening recommendations. Racial
      and ethnic minorities, younger persons, and patients who are less educated or
      have lower health literacy have been found to be less likely to use patient
      portals. CONCLUSION: Additional studies are needed of the utility and
      effectiveness of different elements of web portals for different patient
      populations. This should include additional diseases and health topics such as
      smoking cessation and weight management.

PMID- 28435344
TI  - Development of performance and error metrics for ultrasound-guided axillary
      brachial plexus block.
AB  - PURPOSE: Change in the landscape of medical education coupled with a paradigm
      shift toward outcome-based training mandates the trainee to demonstrate specific
      predefined performance benchmarks in order to progress through training. A valid
      and reliable assessment tool is a prerequisite for this process. The objective of
      this study was to characterize ultrasound-guided axillary brachial plexus block
      to develop performance and error metrics and to verify face and content validity
      using a modified Delphi method. METHODS: A metric group (MG) was established,
      which comprised three expert regional anesthesiologists, an experimental
      psychologist and a trained facilitator. The MG deconstructed ultrasound-guided
      axillary brachial plexus block to identify and define performance and error
      metrics. Experts reviewed five video recordings of the procedure performed by
      anesthesiologists with different levels of expertise to aid task deconstruction.
      Subsequently, the MG subjected the metrics to "stress testing", a process to
      ascertain the extent to which the performance and error metrics could be scored
      objectively, either occurring or not occurring with a high degree of reliability.
      Ten experienced regional anesthesiologists used a modified Delphi method to reach
      consensus on the metrics. RESULTS: Fifty-four performance metrics, organized in
      six procedural phases and characterizing ultrasound-guided axillary brachial
      plexus block and 32 error metrics (nine categorized as critical) were identified
      and defined. Based on the Delphi panel consensus, one performance metric was
      modified, six deleted and three added. CONCLUSION: In this study, we
      characterized ultrasound-guided axillary brachial plexus block to develop
      performance and error metrics as a prerequisite for outcome-based training and
      assessment. Delphi consensus verified face and content validity.

PMID- 28435345
TI  - Practically prepared? Pre-intern student views following an education package: a
      response.

PMID- 28435346
TI  - Mastery learning: how is it helpful? An analytical review.
AB  - The desire to be good at one's work grows out of the aspiration, competition, and
      a yearning to be the best. Surgeons, in their aim to provide the best care
      possible to their patients, adopt this behavior to achieve high levels of expert
      performance through mastery learning, and the surgical training attempts to
      prepare them optimally to lead a virtuous and productive life. The proponents of
      the framework reject evidence that suggests that other variables are also
      necessary to achieve high levels of expert performance. Here, we review various
      models and designs to achieve mastery along with their pros and cons to help us
      understand how mastery learning is helpful in surgical practice.

PMID- 28435347
TI  - Five New Records of Soil-Derived Trichoderma in Korea: T. albolutescens, T.
      asperelloides, T. orientale, T. spirale, and T. tomentosum.
AB  - Despite the huge worldwide diversity of Trichoderma (Hypocreaceae, Ascomycota),
      only about 22 species have been reported in Korea. Thus, between 2013 and 2015,
      soil-derived Trichoderma spp. were isolated to reveal the diversity of Korean
      Trichoderma. Phylogenetic analysis of translation elongation factor 1 alpha gene
      was used for identification. Among the soil-derived Trichoderma, Trichoderma
      albolutescens, T. asperelloides, T. orientale, T. spirale, and T. tomentosum have
      not been previously reported in Korea. Thus, we report the five Trichoderma
      species as new in Korea with morphological descriptions and images.

PMID- 28435348
TI  - Three New Recorded Species of the Physalacriaceae on Ulleung Island, Korea.
AB  - Most known species in the Physalacriaceae are saprotrophs that grow on decaying
      leaves and wood, and approximately 21 genera in the Physalacriaceae have been
      reported worldwide. During an ongoing survey of indigenous fungi in Korea, four
      specimens belonging to the Physalacriaceae were collected on Ulleung Island.
      These specimens were identified as three species based on morphological
      characteristics and molecular analysis of rDNA-internal transcribed spacer
      sequences. Three species in three genera were shown to be new records in Korea:
      Hymenopellis orientalis, Paraxerula hongoi, and Ponticulomyces orientalis. The
      latter two are the first records of these genera in Korea. In this study, we
      provide detailed morphological descriptions of these species and describe their
      phylogenetic position within the Physalacriaceae.

PMID- 28435349
TI  - Proposal of a New Estimation Method of Colonization Rate of Arbuscular
      Mycorrhizal Fungi in the Roots of Chengiopanax sciadophylloides.
AB  - This study proposed a rapid method to quantify the colonization rate of
      arbuscular mycorrhizal fungi (AMF) in plant roots. The method involved the use of
      an image analysis software (WinRHIZO Pro). The colonization rate is defined as
      the ratio of the fungal body to the plant root area in a micrograph. Three
      seedlings of Chengiopanax sciadophylloides, a woody species that accumulates
      radiocesium, were collected from a secondary forest in the Yamakiya district of
      Kawamata, Fukushima Prefecture during May-September 2014. The colonization of AMF
      structures was examined under a light microscope, and the percentage of
      colonization was determined using the WinRHIZO method. The superiority of the new
      method was verified by comparing with a modified grid-line intersect method. The
      colonization of AMF was confirmed in all the seedlings, and a significant
      coefficient of determination (R2 = 0.94) was found with both the methods. The
      results suggested that the WinRHIZO method is reliable for estimating the
      colonization of AMF in C. sciadophylloides.

PMID- 28435350
TI  - Effects of Arbuscular Mycorrhizal Fungi and Soil Conditions on Crop Plant Growth.
AB  - We investigated the effects on various crops of inoculation with species of
      arbuscular mycorrhizal fungi (AMF) in soils from different sources and selected
      AMF species suitable for domestic environment-friendly farming. Effects on plants
      varied with the AMF species used. In carrot, Scutellospora heterogama,
      Acaulospora longula, and Funneliformis mosseae had a positive effect on growth of
      the host, whereas AMF had only weak effects on the growth of red pepper and leek.
      AMF inoculation had positive effects on the growth of carrot and sorghum. The
      results of this study indicate the nature of the relationship between soil,
      plants, and AMF; this study therefore has important implications for the future
      use of AMF in environment-friendly agriculture.

PMID- 28435351
TI  - In Vitro Antifungal Activity of (1)-N-2-Methoxybenzyl-1,10-phenanthrolinium
      Bromide against Candida albicans and Its Effects on Membrane Integrity.
AB  - Metal-based drugs, such as 1,10-phenanthroline, have demonstrated anticancer,
      antifungal and antiplasmodium activities. One of the 1,10-phenanthroline
      derivatives compounds (1)-N-2-methoxybenzyl-1,10-phenanthrolinium bromide (FEN),
      which has been demonstrated an inhibitory effect on the growth of Candida spp.
      This study aimed to explore the in vitro antifungal activity of FEN and its
      effect on the membrane integrity of Candida albicans. The minimum inhibitory
      concentration (MIC) and the minimum fungicidal concentration (MFC) of FEN against
      planktonic C. albicans cells were determined using the broth microdilution method
      according to the Clinical and Laboratory Standards Institute guidelines. Cell
      membrane integrity was determined with the propidium iodide assay using a flow
      cytometer and were visualized using scanning electron microscopy (SEM).
      Planktonic cells growth of C. albicans were inhibited by FEN, with an MIC of 0.39
      1.56 ug/mL and a MFC that ranged from 3.125 to 100 ug/mL. When C. albicans was
      exposed to FEN, the uptake of propidium iodide was increased, which indicated
      that membrane disruption is the probable mode of action of this compound. There
      was cells surface changes of C. albicans when observed under SEM.

PMID- 28435352
TI  - Development of High Cordycepin-Producing Cordyceps militaris Strains.
AB  - Cordyceps militaris, known as Dong-Chong-Xia-Cao, produces the most cordycepin
      among Cordyceps species and can be cultured artificially. For these reasons, C.
      militaris is widely used as herb or functional food in the East Asia. In this
      study, we developed a new strain of C. militaris that produces higher cordycepin
      content than parent strains through mating-based sexual reproduction. Twenty
      parent strains were collected and identified as C. militaris based on internal
      trasncrived spacer and rDNA sequences. Seven single spores of MAT 1-1 idiomorph
      and five single spores of MAT 1-2 idiomorph were isolated from 12 parent strains.
      When 35 combinations were mated on the brown rice medium with the isolated single
      spores, eight combinations formed a stroma with a normal perithecia and confirmed
      mated strains. High pressure liquid chromatography analysis showed that mated
      strain KSP8 produced the most cordycepin in all the media among all the tested
      strains. This result showed due to genetic recombination occurring during the
      sexual reproduction of C. militaris. The development of C. militaris strain with
      increased cordycepin content by this approach can help not only to generate new
      C. militaris strains, but also to contribute to the health food or medicine
      industry.

PMID- 28435353
TI  - Identification and Characterization of Pseudocercospora pyricola Causing Leaf
      Spots on Aronia melanocarpa.
AB  - Leaf spot disease on black chokeberry (Aronia melanocarpa) was observed at
      several locations in Korea during 2014-2015. Leaf spots were distinct, scattered
      over the leaf surface and along the leaf border, subcircular to irregular and
      brown surrounded by a distinct dark color, and were expanded and coalesced into
      irregularly shaped lesions. Severely infected leaves became dry and fell off
      eventually. The causative agent was identified as Pseudocercospora pyricola.
      Morphological observations and phylogenetic analyses of multiple genes, including
      internal transcribed spacer, translation elongation factor 1-alpha, actin, and
      the large subunit ribosomal DNA were conducted. The pathogenicity test was
      conducted twice yielding similar results, fulfilling Koch's postulates. To our
      knowledge, this is the first report on P. pyricola infection of A. melanocarpa
      globally.

PMID- 28435354
TI  - Control Efficacy of Streptomyces sp. A501 against Ginseng Damping-off and Its
      Antifungal Substance.
AB  - Ginseng damping-off, caused by the fungal pathogens Rhizoctonia solani and
      Pythium sp., is a critical disease in ginseng seedling. In a continuing effort to
      find microorganisms with the potential of acting as a biocontrol agent against
      Rhizoctonia damping-off, we found that a Streptomyces sp. A501 showed significant
      antifungal activity against Rhizoctonia solani. In field experiment to test the
      efficacy of Streptomyces sp. A501 in controlling ginseng damping-off, the
      incidence of damping-off disease was meaningfully reduced when ginseng seeds were
      soaked in the culture broth of Streptomyces sp. A501 before sowing. To perform
      characterization of the antifungal compound, we isolated it from the culture
      broth of strain A501 through Diaion HP-20 and silica gel column chromatographies
      and preparative high-performance liquid chromatography. The structure of the
      antifungal compound was assigned as fungichromin by spectroscopic methods, mainly
      nuclear magnetic resonance and electrospray ionization-mass analysis.

PMID- 28435355
TI  - Optimization of Fungal Enzyme Production by Trichoderma harzianum KUC1716 through
      Surfactant-Induced Morphological Changes.
AB  - The morphological optimization of Trichoderma harzianum was carried out using
      several surfactants to achieve increased cellulase production. Addition of the
      surfactants to the culture medium successfully modified the fungal morphology
      from an aggregated form to a dispersed form. Optimization of the fungal
      morphology increased cellulase activity up to 177%. The morphologically optimized
      conditions enhanced the accessibility of the fungus to substrates and thus
      promoted cellulase production.

PMID- 28435356
TI  - Screening and Production of Manganese Peroxidase from Fusarium sp. on Residue
      Materials.
AB  - In this study, we report the manganese peroxidase production ability from a
      Fusarium sp. strain using an inexpensive medium of agriculture residues of either
      rice straw or wood chips as carbon source. The highest manganese peroxidase
      activity on rice straw medium and on wood chips was 1.76 U/mL by day 9 and 1.91
      U/mL by day 12, respectively.

PMID- 28435357
TI  - Effectiveness of audiovisual distraction with computerized delivery of anesthesia
      during the placement of stainless steel crowns in children with Down syndrome.
AB  - OBJECTIVE: Assessing effectiveness of audiovisual (AV) distraction with/without
      video eyewear and computerized delivery system-intrasulcular (CDS-IS) for local
      anesthesia during placement of stainless steel crowns for the management of
      pathological tooth grinding in children with Down syndrome. MATERIALS AND
      METHODS: This clinical study includes 22 children (13 boys and 9 girls), with
      mean age being 7.1 years. The study involved three sessions 1-week apart. During
      Session I, dental prophylaxis to the upper jaw was done while watching a movie
      projected on the ceiling without video eyewear whereas prophylaxis for the lower
      jaw and impressions of both jaws were taken while watching another movie using
      eyewear projection. After 1 week, during Session II/III, children had their upper
      and lower second primary molars which were prepared and steel crowns inserted,
      respectively, while watching movies which were projected using video eyewear
      under the effect of CDS-IS local anesthesia. Changes in pulse oximeter and heart
      rate were recorded every 5 min. Independent sample t-test was used to assess
      significance of changes during each visit. RESULTS: A statistically significant
      difference (P < 0.03) was observed in mean pulse rate between dental prophylaxis
      without video eyewear and during dental prophylaxis and dental impression taken
      while children were distracted using AV distracter with video eyewear. We
      observed an increase in mean pulse rate during tooth preparation use dental
      drills, but this does not lead to disruptive behavior as children were being
      distracted by AV distracter with video eyewear. CONCLUSION: Routine psychological
      (Tell-Show-Do) intervention along with visual distraction using video eyewear and
      use of CDS-IS system for anesthetic delivery is recommended as an effective
      behavior management technique for children with Down syndrome during invasive
      dental treatment.

PMID- 28435358
TI  - Effect of cleaning agent, primer application and their combination on the bond
      strength of a resin cement to two yttrium-tetragonal zirconia polycrystal
      zirconia ceramics.
AB  - OBJECTIVE: The objective of this study is to evaluate the effect of a cleaning
      agent and priming on the bond strength (BS) of a resin cement (RC) to zirconia
      ceramics after 24 h and 1 year of water-storage. MATERIALS AND METHODS: Fifty-six
      Katana and 56 ZirCAD zirconia ceramic plates were prepared and each zirconia
      brand was divided into four groups (n = 14): (1) untreated; (2) treated with
      Ivoclean cleaning agent; (3) treated with Monobond Plus coupling agent; (4)
      treated with Ivoclean + Monobond Plus. Cleaning and coupling agents were applied
      to zirconia following the manufacturers' instructions. The RC was manipulated,
      inserted into tubes (0.75 mm diameter/1 mm height) that were positioned on the
      zirconia surfaces and light activated. Specimens were tested after 24 h and 1
      year of water storage. A shear load was applied to the base of the RC cylinders
      (until failure. Data were analyzed by three-way ANOVA and Tukey tests (alpha =
      5%). RESULTS: No significant difference in BS was noted between zirconia
      ceramics, except when the combination of cleaning and coupling agents was used.
      This combination increased the BS for Katana zirconia. One year of water storage
      leads to a decrease in BS for all experimental groups. CONCLUSION: The
      combination of cleaning agent and priming can yield higher BS for Katana at 24 h.
      BS to zirconia ceramics reduced approximately 50% after 1 year.

PMID- 28435359
TI  - Comparative antimicrobial efficacy of selected root canal irrigants on commonly
      isolated microorganisms in endodontic infection.
AB  - OBJECTIVE: This study aims to evaluate and compare the antimicrobial efficacy of
      three selected root canal irrigants (BioPure MTAD, metronidazole, aztreonam)
      against microbes commonly isolated from polymicrobial microbiota of root canal
      infection. MATERIALS AND METHODS: This study was designed with four experimental
      groups (Group I - Bacteroides fragilis, Group II - Propionibacterium acnes, Group
      III - Enterococcus faecalis, Group IV - Candida albicans) based on the microbes
      selected for the study. Group I and Group II bacteria were used to compare and
      evaluate antimicrobial effect of BioPure MTAD, metronidazole, aztreonam, and
      normal saline. Group III and Group IV bacteria were used to compare and evaluate
      antimicrobial efficacy of BioPure MTAD, aztreonam, and normal saline. Normal
      saline was used as a control irrigant in this study. Agar disc diffusion method
      was applied to assess and compare the antimicrobial action of selected irrigants.
      RESULTS: Metronidazole was found to be the most effective root canal irrigant
      against B. fragilis and P. acnes among the tested irrigants. Mean zone of
      inhibition against E. faecalis has been shown to be maximum by BioPure MTAD,
      followed by aztreonam. Antifungal effect against C. albicans was only shown by
      BioPure MTAD. CONCLUSIONS: Overall, BioPure MTAD is the most effective root canal
      irrigant as it has shown an antibacterial effect against all the tested
      microorganisms. However, metronidazole showed maximum antibacterial effect
      against obligate anaerobes. Aztreonam also showed an antibacterial effect in the
      present study, raising its possibility to be used as a root canal irrigant in the
      future.

PMID- 28435360
TI  - The confidence of undergraduate dental students in Saudi Arabia in performing
      endodontic treatment.
AB  - OBJECTIVE: This study examined the endodontic experience, perceptions of
      endodontic practice, and self-rated confidence of dental students enrolled in
      Taibah University, Saudi Arabia. MATERIALS AND METHODS: A questionnaire was
      distributed to 41 undergraduate dental students registered in endodontic courses
      in the 2015 academic year. The questionnaire evaluated their confidence
      performing nonsurgical root canal treatment. The level of confidence was
      classified using a 5-point scale as "very confident," "confident," "neutral,"
      "not very confident," or "not at all confident." The data were analyzed using
      SPSS version 20.0 (SPSS, Chicago, IL, USA). RESULTS: The participation rate was
      93%. The maxillary incisor was the most common first tooth treated. The students
      were relatively confident, but their confidence levels were lower regarding
      endodontic radiology, evaluation of root canal obturation, and determining the
      correct recall period for the patient. CONCLUSION: The confidence of
      undergraduates in endodontics must be enhanced to increase their clinical
      competence when performing root canal treatment.

PMID- 28435361
TI  - Effects of delivering the same radiant exposures at 730, 1450, and 2920 mW/cm2 to
      two resin-based composites.
AB  - OBJECTIVE: To evaluate the effects of curing two resin-based composites (RBC)
      with the same radiant exposures at 730, 1450, and 2920 mW/cm2. MATERIALS AND
      METHODS: Two types of RBC, Filtek Supreme Ultra and Tetric-EvoCeram-Bulk Fill,
      were light-cured to deliver the same radiant exposures for 5, 10, or 20 s by
      means of a modified Valo light emitted diode light-curing unit with the light tip
      placed directly over each specimen. The RBC was expressed into metal rings that
      were 2.0 and 4.0 mm in thickness, directly on an attenuated total reflectance
      Fourier transform infrared plate heated to 33 degrees C, and the degree of
      conversion (DC) of the RBC was recorded. The specimens were then removed and the
      Knoop microhardness (KHN) was tested at both the bottom and the top of each
      specimen. The KHN was tested again after 24 h and 7 days of storage in the dark
      at 37 degrees C and 100% humidity. The DC and KHN results were analyzed with
      Fisher's protected least significant difference at alpha = 0.05. RESULTS: The DC
      values for the specimens cured at the three different irradiance levels were
      similar. However, at different depths, there were differences in the DC values.
      In general, there were no clear differences among the samples cured in the three
      different groups, and the KHN was always greater 24 h and 7 days later (P <
      0.05). CONCLUSIONS: Despite the curing time, and as long as the samples were
      cured with the same radiant exposures, there were no significant effects on the
      DC and KHN of both RBCs.

PMID- 28435362
TI  - Awareness about the effects of tobacco consumption on oral health and the
      possibility of smoking behavior among male Saudi schoolchildren.
AB  - OBJECTIVE: To investigate an association between the awareness about the effects
      of tobacco consumption on oral health and the likelihood of smoking among male
      schoolchildren. MATERIALS AND METHODS: A cross sectional study was conducted
      using a multistage random sampling technique. The participants (ages 15-19 years)
      were recruited from male public high schools in Greater Dammam in Saudi Arabia. A
      pretested questionnaire inquired participants' awareness about the effects of
      smoking on oral health. SPSS (Released 2013, IBM SPSS Statistics for Windows,
      Version 22.0. Armonk, NY: IBM Corp) was used to calculate unadjusted and adjusted
      odds ratio (OR) and 95% confidence interval (CI). Multiple logistic regression
      and interaction analyses were performed to identify the factors associated with
      the probability of smoking behavior among children. RESULTS: More than 69.9% (n =
      277) of participants were aware of the adverse effects of tobacco consumption on
      oral health which included poor oral health, bad taste and breath, periodontal
      disease, dental caries, oral ulcers, and oral cancers. The odds of smoking were
      22%-47% lower among schoolchildren who were aware of the consequences of smoking
      on oral health than those who were unaware of these complications. The students
      who believed that smoking can cause oral ulcers and negatively affects oral
      health had a lower probability of smoking (OR: 0.414; CI: 0.201-0.50) and (OR:
      0.433; CI: 0.194-0.965), respectively in comparison with those who thought that
      smoking had no such negative impacts. CONCLUSIONS: Schoolchildren with increased
      awareness of smoking effects on oral health were less likely to smoke. Educating
      students about the complications of smoking on oral health should be the part of
      smoking cessation programs and policies.

PMID- 28435363
TI  - Lightness, chroma, and hue distributions in natural teeth measured by a
      spectrophotometer.
AB  - OBJECTIVE: The aim of the study was to analyze the distribution of color
      parameters, lightness (L*), chroma (C), hue (H), a* and b*, in the intercanine
      sector in maxilla. MATERIAL AND METHODS: Patients' tooth color measurements were
      performed using an intraoral spectrophotometer VITA Easyshade(r) (VITA Zahnfabrik
      H. Rauter GmbH and Co. KG, Bad Sackingen, Germany). The measurements were made in
      255 subjects in the intercanine sector in maxilla. RESULTS: The mean values for
      the group of 255 subjects were as follows: L*, a*, b*, C, and H as 81.6, 0.67,
      21.6, 21.7, and 92.7, respectively. For F=206.27 and P < 0.001 between L*, a*,
      b*, C, H, and central incisor/lateral incisor/canines, there were statistically
      significant differences. CONCLUSION: With the statistical analysis, it was
      determined that there are significant color differences between the teeth of the
      intercanine sector, which differences are clinically significant also.

PMID- 28435364
TI  - Influence of reuse and cervical preflaring on the fracture strength of
      reciprocating instruments.
AB  - OBJECTIVE: This study sought to assess the influence of cervical preflaring and
      reuse after resterilization, on fracture strength and plastic deformation and/or
      surface cracking in reciprocating nickel-titanium [NiTi] endodontic instruments
      after root canal instrumentation of extracted human teeth. MATERIALS AND METHODS:
      Forty engine-driven reciprocating NiTi instruments (20 Reciproc(r) [RC], VDW; 20
      WaveOne(r) [WO], Dentsply) were used in root canal instrumentation of extracted
      human molars. A total of 485 human upper molars with similar anatomical features
      were selected and randomly distributed across four groups according to the
      instrumentation procedures performed (G1 and G3: RC; G2 and G4: WO).
      Reciprocating instruments were used as per manufacturer instructions. In groups
      G3 and G4, cervical preflaring was performed prior to instrumentation. After each
      use of each instrument, sterilization was repeated and scanning electron
      microscope (SEM) images were obtained to check for plastic deformations and/or
      cracks on instrument surfaces. Each instrument was used repeatedly until fracture
      occurred. RESULTS: Regardless of flaring, RC files exhibited greater fracture
      strength than WO instruments (P <0.01) with and without preflaring. Cervical
      preflaring significantly reduced the risk of instrument fracture (P <0.01). No
      plastic deformations were observed before fracturing. However, cracks were found
      on WO instruments shortly after their first use. RC and WO instruments resisted
      fracturing after autoclave sterilization. CONCLUSIONS: Cervical preflaring
      allowed a significant increase in the number of times RC and WO files could be
      reused safely.

PMID- 28435365
TI  - Can onlay's be an alternative restoration for severely damaged primary teeth.
AB  - OBJECTIVE: The aim of this study was to evaluate indirect compomer and composite
      resin onlay restorations of severely damaged primary molars in vivo. MATERIALS
      AND METHODS: At the study, 48 restorations, in seven girls and ten boys totally
      17 patients aged 4-8, was evaluated clinically with using USPHS criteria for 15
      months. RESULTS: The study results revealed that the clinical success rate of
      compomer and composite onlay restorations was 79% and 96%, respectively. No
      significant differences were found statistically between the materials.
      CONCLUSIONS: In the children severely damaged primary molars, onlays are usually
      worked with an indirect technique in clinics. One of the advantages of indirect
      technique is being most similar to its original form morphologically.

PMID- 28435366
TI  - Comparative evaluation of antimicrobial efficacy of triple antibiotic paste,
      calcium hydroxide, and a proton pump inhibitor against resistant root canal
      pathogens.
AB  - OBJECTIVE: The objective of this study is to compare the antimicrobial efficacy
      of triple antibiotic paste (TAP) and a proton pump inhibitor (PPI) (omeprazole)
      in combination with calcium hydroxide (CH) against Enterococcus faecalis and
      Candida albicans. MATERIALS AND METHODS: E. faecalis and C. albicans were
      subcultured and inoculated at 37 degrees  overnight and were treated with
      different dilutions of TAP, 25 MUg/ml (Group 1), CH (Group 2, control), CH 16
      mg/ml + omeprazole 2 mg/ml (Group 3a) (CH 16 mg/ml + omeprazole 4 mg)/ml (Group
      3b) for 24, 48, and 72 h in sterile uncoated 96-well microtiter plates. Minimum
      concentration at which the medicaments produced least optical density was
      determined using ELISA reader (ELx 808 BioTek Inc., USA) device set at optical
      density of 630 nm. Results were analyzed statistically by one-way analysis of
      variance followed by Tukey's multiple comparison tests. The significance level
      was set at 0.05. RESULTS: Mean concentration (irrespective of time) for TAP at
      which mean minimum optical density was recorded at 1.25 MUg/ml (1:20 dilution)
      and 25 MUg/ml (0 dilution) against E. faecalis and C. albicans, respectively.
      Least optical density for CH plus PPI group was obtained 1.6 MUg/ml (1:10
      dilution) and 16 MUg/ml (0 dilution) for E. faecalis and C. albicans,
      respectively. However, CH alone showed a weaker antimicrobial action against
      either of the strains even at full concentration. CONCLUSIONS: PPI enhanced the
      antibacterial efficacy of CH against E. faecalis and C. albicans. However, TAP
      showed the best antibacterial property followed by CH plus PPIs against both the
      selected strains.

PMID- 28435367
TI  - "Ormocer an innovative technology": A replacement for conventional cements and
      veneer? A comparative in vitro analysis.
AB  - OBJECTIVE: This in vitro study was designed to assess shear bond strength (SBS)
      of ormocer flowable (OF) resin as a luting agent, ormocer as an indirect veneer
      material with portrayal of modes of failures using scanning electron microscope
      (SEM). MATERIALS AND METHODS: Sixty maxillary central incisors were divided into
      Group I, II, and III with 20 samples each based on luting cement used. They were
      OF, self-adhesive (SA) cement, and total etch (TE) cement. These groups were
      subdivided into "a" and "b" of ten each based on the type of veneering materials
      used. Veneer discs were fabricated using Ormocer restorative (O) and pressable
      ceramic (C). Specimens were thermocycled and loaded under universal testing
      machine for SBS. The statistical analysis was done using one-way ANOVA post hoc
      Tukey honest significant difference method. RESULTS: A significant difference was
      observed between the Groups I and II (P < 0.05). The highest mean bond strength
      when using ormocer veneer was obtained with the Group Ia (19.11 +/- 1.92 Mpa) and
      lowest by Group IIa (8.1 +/- 1.04 Mpa), whereas the highest mean bond strength
      while using ceramic veneer was of similar range for Group Ib (18.04 +/- 4.08 Mpa)
      and Group IIIb (18.07 +/- 1.40 Mpa). SEM analysis revealed OF and TE presented
      mixed type of failure when compared with SA where failure mode was totally
      adhesive. CONCLUSION: OF was found equally efficient like TE. Bond strength of
      ormocer as a veneer was not inferior to ceramic making it one of the promising
      additions in the field of dentistry.

PMID- 28435368
TI  - Correlation between frontal sinus dimensions and cephalometric indices: A cross
      sectional study.
AB  - OBJECTIVE: Growth prediction plays a significant role in accurate diagnosis and
      treatment planning of orthodontics patients. It was hypothesized that the unique
      pattern of pneumatization of the frontal sinus as a component of craniofacial
      structure would influence the skeletal growth pattern and may be used as a growth
      predictor. MATERIALS AND METHODS: A total of 144 subjects (78 females and 66
      males) with a mean age of 19.26 +/- 4.66 years were included in this
      retrospective study. Posterior-anterior and lateral cephalograms (LCs) were used
      to measure the frontal sinus dimensions. The skeletal growth pattern and
      relations of craniofacial structures were analyzed on LC using variables for
      sagittal and vertical analyses. Correlation between the frontal sinus dimensions
      and cephalometric indices was assessed by the Pearson's correlation coefficient.
      RESULTS: The SN-FH and SNA angles had significant associations with frontal sinus
      dimensions in all enrolled subjects (P < 0.05). In males, the SN-FH, sum of
      posterior angles, Pal-SN, and Jarabak index were significantly associated with
      the size of frontal sinus (P < 0.05). In females, the associations of SN-FH and
      gonial angles with frontal sinus dimensions were significant (P < 0.05).
      CONCLUSION: The results show that larger size of frontal sinus was associated
      with reduced inclination of the anterior cranial base, increased anterior facial
      height (in males), and increased gonial angle (in females) in the study
      population.

PMID- 28435369
TI  - In vitro comparative evaluation of different storage media (hank's balanced salt
      solution, propolis, Aloe vera, and pomegranate juice) for preservation of avulsed
      tooth.
AB  - OBJECTIVES: Prognosis of the avulsed teeth is mostly affected by extraoral dry
      period and storage medium used to store teeth before reimplantation. However,
      ability of storage media can affect cell viability and success of treatment.
      Various storage media were tried with some success. The present study was
      undertaken to comparatively evaluate the efficacy of hank's balanced salt
      solution (HBSS), propolis, Aloe vera, and pomegranate juice (PJ) in preserving
      the vitality of periodontal ligament (PDL) cells of avulsed teeth. MATERIALS AND
      METHODS: Fifty orthodontically extracted sound teeth with healthy PDL were
      selected for the present study. Selected teeth were randomly divided into study
      groups (10 in each) and 5 each as positive and negative control groups. All the
      teeth were immersed immediately after extraction into respective storage media.
      Data were statistically analyzed using IBM SPSS software for Windows, Version
      19.0., IBM Corp., Armonk, NY, USA. Analysis of variance and multiple range were
      done using Tukey's honestly significant difference with level of significance at
      5% (P > 0.05). RESULTS: Propolis (285,000 viable cells with standard deviation
      4.11028 and standard error of 1.38097) showed more viable PDL cells followed by
      HBSS, A. vera, and PJ. CONCLUSION: Propolis, A. vera, and PJ can be used as an
      alternative tooth storage media.

PMID- 28435370
TI  - Facial profile and maxillary arch dimensions in unilateral cleft lip and palate
      children in the mixed dentition stage.
AB  - OBJECTIVES: The aim of this study was to evaluate the vertical and sagittal
      facial profile and maxillary arch width, depth, and length of patients with
      unilateral cleft lip and palate (UCLP) and to compare them with healthy noncleft
      children in the mixed dentition stage (7-13 years). MATERIALS AND METHODS: This
      study is conducted at Hospital Universiti Sains Malaysia. UCLP group comprised 48
      patients with nonsyndromic UCLP who have had the lip and palate repaired, whereas
      the control group comprised 48 healthy noncleft cases. The lateral cephalometrics
      measurements were used to determine the vertical height, sagittal depth of the
      face, and cranial base length and angle. Maxillary arch dimensions were measured
      on the study cast including arch width, depth, and length. RESULTS: Vertical
      facial height and sagittal depth measurements showed a significant decrease (P <
      0.05) in the mean growth pattern in UCLP group. The anterior cranial base length
      (S-N) was shorter in UCLP children (P < 0.001), while Ba-N length had no
      significant difference (P = 0.639). Nasion-Sella Tursica-Basion angle was
      significantly higher in the UCLP group (P = 0.016). Dental arch width with
      reference to canine-to-canine and first premolar-to- first premolar distance was
      significantly larger in control (P = 0.001). CONCLUSION: Mean vertical and
      sagittal facial dimensions in the UCLP children who do not undergo orthodontic
      treatment are significantly lesser in all directions of growth than healthy
      noncleft children. The maxillary dental arch had a normal depth but constricted
      in width and arch length.

PMID- 28435371
TI  - Attitude and knowledge of isolation in operative field among undergraduate dental
      students.
AB  - OBJECTIVE: The purpose of this study was to evaluate the general attitude of
      undergraduate dental students toward rubber dam use, specifically focusing on
      operative procedures before starting to serve community. METHODS: Questionnaires
      were distributed to undergraduate clinical years' students of two private
      colleges; Al-Farabi Dental College, Riyadh, KSA and Buraidah Private Colleges,
      Qassim, KSA. Questions were asked about areas where the students used rubber dam
      in operative procedures, in which types of caries classes, and in which type of
      restoration they frequently used the rubber dam. RESULTS: We found that students
      of both private dental colleges agreed with the opinions that proper isolation
      cannot be achieved for the restoration of operative procedures without using
      rubber dam and restoration placed under rubber dam have a greater longevity than
      those placed without. CONCLUSIONS: Within the limitations of the present study,
      it can be concluded that the perceptions of dental students on rubber dam need to
      be improved and strategies should be developed so that this valuable adjunct will
      comprise one of the indispensable elements of dental care.

PMID- 28435372
TI  - Histologic evaluation of the effect of mineral trioxide aggregate-Fillapex as a
      root canal sealer in rat teeth submitted to late replantation.
AB  - OBJECTIVE: This study aims to analyze the effect of new root canal based silicate
      cement, in rat teeth after late replantation, comparing with calcium hydroxide
      (CH) in preventing tooth root resorption. MATERIALS AND METHODS: The study group
      included 16 Wistar rats in which the upper right central incisors were extracted
      and were left on a worktable for 60 min, simulating a case of tooth avulsion,
      after had been anesthetized. One group, (Group I), the canals were filled with CH
      past, before replantation. The second groups of teeth, (Group II), the canals
      were filled with mineral trioxide aggregate-Fillapex (MTAF). After removal, the
      blood clot of the socket, with saline solution irrigation, the teeth were
      replanted into their original socket, and splinted with silk 3/0. The rats were
      sacrificed 8 weeks after replantation and the specimens were prepared for
      histologic and histomorphometric analyses. The areas of inflammatory and
      replacement resorptions were selected and quantified. These data for each group
      of teeth were evaluated and analyzed using the Mann-Whitney test (P = 0.05).
      RESULT AND CONCLUSION: All the replanted teeth in both groups survived. Although
      root canal filled with MTAF provide better results than with CH past concerning
      inflammatory and replacement resorption, there was no statistical difference (P =
      0.527).

PMID- 28435373
TI  - Comparative clinical efficacy of three toothpastes in the control of
      supragingival calculus formation.
AB  - OBJECTIVES: The purpose of this double-blind, parallel clinical study was to
      assess clinical efficacy in supragingival calculus formation reduction using
      Abhaibhubejhr Herbal Toothpaste compared to Colgate Total and Colgate Cavity
      Protection toothpastes. MATERIALS AND METHODS: A total of 150 subjects
      participated in the pretest phase. All subjects were given oral soft/hard tissue
      evaluation, calculus examination using Volpe-Manhold calculus, and whole mouth
      oral prophylaxis. They received noncalculus control fluoride toothpaste and a
      soft-bristled toothbrush to brush for 1 min two times daily for 8 weeks. After
      which, subjects were given a test phase oral soft/hard tissue evaluation and
      calculus examination and were randomized into one of the three toothpaste groups.
      All subjects in the test phase received a whole mouth oral prophylaxis and were
      given their assigned toothpaste and a soft-bristled toothbrush to brush for 1 min
      two times a day for 12 weeks. Thereafter, subjects were assessed for their oral
      soft/hard tissue and calculus formation. RESULTS: Mean Volpe-Manhold calculus
      index scores for the Cavity Protection, Abhaibhubejhr, and Total toothpaste
      groups were 0.78, 0.62, and 0.48, respectively, at the 12-week test phase
      evaluation. Abhaibhubejhr and Total toothpaste groups show 20.51% and 38.46%
      significantly less calculus formation than the Cavity Protection toothpaste group
      (P < 0.05). Total toothpaste group also show 22.58% significantly less calculus
      formation than the Abhaibhubejhr toothpaste group (P < 0.05). CONCLUSION: The use
      of Colgate Total toothpaste over a 12-week period was clinically more effective
      than either Abhaibhubejhr or Colgate Cavity Protection toothpastes in controlling
      supragingival calculus formation.

PMID- 28435374
TI  - Spatial analysis of mandibular condyles in patients with temporomandibular
      disorders and normal controls using cone beam computed tomography.
AB  - OBJECTIVES: The aim of the study is to investigate the condylar position and its
      relation to articular eminence and axial condylar angle in temporomandibular
      joint disorder (TMD) patients and in normal controls using cone beam computed
      tomography (CBCT). MATERIALS AND METHODS: CBCT temporomandibular joint (TMJ)
      images of 70 participants (38 males and 32 females, mean age 26.4 years) were
      analyzed. They were divided into control group (including 35 subjects) and study
      group (including 35 subjects). Linear measurements of joint space and condyle
      determined the condylar position of each TMJ. Articular eminence height and
      inclination were also measured with axial condylar angle to determine its
      relation to condylar position. Independent and paired sample t-test was applied
      to compare between the groups and TMJ sides of the same group at significance
      level of 0.05. RESULTS: Statistical significant differences were found between
      males and females of both groups regarding superior joint space (SJS), lateral
      joint space, A-P, and M-L condyle distance (P < 0.05). SJS, medial joint space
      (MJS), and eminence angle were greater (P < 0.01) in male's joints with TMD with
      flatter axial condylar angle (P < 0.05), when compared with normal TMJ
      counterpart. Females TMJs showed significantly higher values of MJS of affected
      side when compared with normal counterpart with flatter axial condylar angle (P <
      0.05). CONCLUSION: Superior and MJS parameters were the ones that showed
      significant differences between affected and nonaffected joints. The mean axial
      condylar angle was smaller in joints with abnormal TMJ. This indicates that the
      condyles of the affected joints may rotate inward.

PMID- 28435375
TI  - Knowledge, attitude, and practice of pediatricians regarding pediatric liquid
      medicaments.
AB  - OBJECTIVE: To assess the knowledge, attitude, and practice of pediatricians
      regarding pediatric liquid medicaments (PLMs) and its effect on dental health.
      MATERIALS AND METHODS: A convenience sample of 103 pediatricians was asked to
      answer a questionnaire. RESULTS: A total number of 87 pediatricians completed the
      questionnaires. They considered age and body weight of the child (58%), cost of
      the medicine (40%), and pharmaceutical company (37%) to be relevant while
      prescribing. Eighty-eight percent of pediatricians knew that the PLM was sweet in
      nature. Sixty-seven percent of pediatricians stated that pH of PLM is responsible
      for deleterious effect on teeth. Seventy-two percent of pediatricians were aware
      of hidden sugars present in PLM. Only 48% of pediatricians were aware of
      availability of sugar-free medicine. Seventy percent of pediatricians were of the
      opinion that sugar-free medicine is not as sweet as sugar-containing medicines
      and is more expensive (65%). CONCLUSION: Knowledge, attitude, and practice of
      pediatricians regarding PLMs and its effect on dental health were not
      satisfactory.

PMID- 28435376
TI  - Comparative evaluation of antimicrobial efficacy of an alternative natural agent
      for disinfection of toothbrushes.
AB  - OBJECTIVE: The aim of this study was to assess the antimicrobial potency of
      aqueous extract of Psidium guajava leaves in two different concentrations as a
      toothbrush disinfectant against three oral bacterial species. MATERIALS AND
      METHODS: Aqueous extracts of P. guajava leaves were prepared at 20% and 30%
      concentrations and 0.2% chlorhexidine was used as control. The toothbrushes were
      equally divided into 9 groups with 10 toothbrushes per disinfectant, which were
      contaminated with Streptococcus mutans, Lactobacillus acidophilus, and
      Enterococcus faecalis. Microbial culture was done after 5 min and 3 h of
      decontamination. RESULTS: Group Ia and Ib showed that the presence of E. faecalis
      was observed in 8 (40%) of 20 toothbrushes. Group IIa and IIb showed a
      significant reduction in colony forming unit/toothbrush during 3 h evaluation.
      Group IIIa and IIIb showed nil growth during 3 h evaluation. Nil growth was
      observed with the control group for all three organisms. Statistically
      significant values were obtained for 5 min (P < 0.001) and 3 h (P < 0.001)
      disinfection period against L. acidophilus at two different concentrations.
      CONCLUSION: Aqueous extracts of guava leaves can be used as an alternative
      organic product for disinfection of toothbrushes.

PMID- 28435377
TI  - Frequency of impacted teeth and categorization of impacted canines: A
      retrospective radiographic study using orthopantomograms.
AB  - OBJECTIVE: The objective of this study is to determine the frequency of impacted
      maxillary canines using seven subtype classification system. For this purpose,
      impacted maxillary canines have been divided into seven various subtypes.
      MATERIALS AND METHODS: This is a descriptive, cross-sectional, and retrospective
      study conducted using radiographic data of residents of Madinah, Al Munawwarah.
      Radiographic data of 14,000 patients, who attended College of Dentistry, Taibah
      University, from January 2011 to February 2015, were screened against the
      selection criteria for the presence of impacted teeth. The individuals with
      maxillary impacted canines were matched to maxillary canine impaction. The
      occurrence of each subtype of impacted canines was calculated. RESULTS: Impacted
      teeth are more common in the maxilla compared to mandible. The impacted canine
      represented the highest proportion of all impacted maxillary teeth followed by
      the second premolars and the central incisors. According to the classification
      system represented, Type II of canine impaction comprised the highest proportion
      (51%) while Type IV (0.5%) comprised the lowest frequency. The maxillary canine
      is the most frequently impacted tooth followed by mandibular canines.
      CONCLUSIONS: Although there are many variations, the majority of impacted canines
      fall into Type II of the classification of impacted canines.

PMID- 28435378
TI  - Differentiating spontaneous vertical root fracture in endodontically treated
      tooth.
AB  - Although vertical root fracture (VRF) is mostly found in endodontically treated
      teeth, it also occurs spontaneously. If VRF is recognized after endodontic
      treatment, it is considered to be iatrogenic and can lead to legal trouble.
      However, legal problems can be averted if the dentist can prove that the VRF
      existed before endodontic treatment. This case report describes an unusual,
      spontaneous VRF in an endodontically treated tooth and presents a useful tip for
      determining whether a fracture is iatrogenic. We performed nonsurgical endodontic
      treatment on a mandibular first molar with irreversible pulpitis. After 6 months,
      the patient revisited with localized swelling, and we diagnosed VRF of the mesial
      root. We extracted the tooth and prepared it for microscopic examination. We
      found gutta-percha in the fracture line of the transversely sectioned root, and
      it appeared to have penetrated to the fracture line through the force generated
      from the filling. The patient was informed and agreed that the fracture occurred
      spontaneously before treatment. This case demonstrates the time point of VRF
      occurrence by identifying the presence of gutta-percha in the fracture line. We
      suggest that this procedure can be used to demonstrate whether VRFs in
      endodontically treated teeth are spontaneous or iatrogenic.

PMID- 28435379
TI  - Shifts of subgingival bacterial population after nonsurgical and pharmacological
      therapy of localized aggressive periodontitis, followed for 1 year by Ion Torrent
      PGM platform.
AB  - The possibility of targeting the hypervariable region V3 of the 16S rRNA gene
      using Ion Torrent Personal Genome Machine (PGM) could provide a complete analysis
      of subgingival plaque samples, potentially able to identify microbiological
      species missed by culture-based methods. A 16-year-old female smoker patient,
      affected by localized aggressive periodontitis, underwent a full-mouth
      disinfection protocol and was inserted in a 3-month recall program.
      Microbiological samples were collected at baseline and at 30, 100, 365 days
      follow-up and analyzed by Ion Torrent PGM. Capnocytophaga, Fusobacterium,
      Prevotella, and Treponema were the most represented pathogens at baseline.
      Nonsurgical treatment and systemic antibiotics drastically lowered the anaerobic
      species, and their presence remained limited after 100 days, while a consistent
      recolonization by anaerobic bacteria was detected at 365 days. The patient showed
      a general improvement of periodontal conditions. Differently from polymerase
      chain reaction and other microarray techniques, Ion Torrent performs a
      quantitative analysis of the microbiota, irrespective of the searched species. An
      accurate definition of the shifts of the bacterial community might help
      periodontal researchers for a better understanding of the impact of different
      treatment approaches or in intercepting nonresponsive conditions.

PMID- 28435380
TI  - A comparative assessment of prosthetic outcome on enucleation and evisceration in
      three different etiological eye defects: A case series.
AB  - Enucleation and evisceration are the most common surgical procedures that are
      performed to manage tumor, trauma, and infection. Given the consequences of
      surgical intervention, the conditions of the remaining eye socket may affect
      future prosthetic rehabilitation. A custom-made ocular prosthesis can be used to
      help restore the esthetics and functional defects and to improve the quality of
      life of patients with such conditions. An assessment must be performed on the
      prosthetic outcome before rehabilitation. The etiology of defect, type of
      surgery, condition of the remaining socket, and patient's age should all be
      considered. This report discusses three different etiological eye defects that
      have undergone enucleation and evisceration and describes the factors that have a
      significant role in the esthetic and functional outcome of the prosthesis. This
      report should serve as a helpful aid for maxillofacial prosthodontists to
      understand the primary objective of rehabilitating each eye defect and to meet
      patient expectations.

PMID- 28435382
TI  - Myobiid mites (Trombidiformes, Myobiidae) of the golden bat Mimon cozumelae from
      Mexico. Description of the male and tritonymph of Ioanella mimon and new records
      of Eudusbabekia mimon.
AB  - The male and the tritonymph of Ioanella mimon are described for the first time
      parasitizing to Mimon cozumelae from Yucatan, Mexico. Male of Ioanella mimon is
      characterized by the presence of legs I with the tibia and tarsus fused forming a
      small complex devoided of apical claws, legs II-IV with two claws, setae vi at
      level of anterior end of genital plate, genital plate rounded with an anterior
      projection, all intercoxal setae short; while the tritonymph is characterized by
      the presence of legs I unequal; legs II-IV with 2-1-1 claws, and posterior region
      of dorsal idiosoma with 3 pairs of cylindrical and toothed setae. Additionally,
      we include new locality and host records for Eudusbabekia mimon which was also
      found on Mimon cozumelae. Both species were described originally in association
      with Mimon bennettii at Bartica, Guyana.

PMID- 28435383
TI  - A review of the Neotropical genus Bidessodes Regimbart, 1895 including
      description of four new species (Coleoptera, Adephaga, Dytiscidae, Hydroporinae,
      Bidessini).
AB  - The Neotropical genus Bidessodes Regimbart, 1895 is reviewed. Four new species
      are described, Bidessodes chlorus Miller, sp. n., Bidessodes erythros Miller, sp.
      n., Bidessodes leukus Miller, sp. n., and Bidessodes melas Miller, sp. n.,
      bringing the total number of species in the genus to 20. A key to species is
      provided. Important diagnostic features are illustrated and described and
      distributions of all species based on examined specimens and published records
      are provided. Recognition of the subgenera of Bidessodes is not justified, and
      the two names Hughbosdineus Spangler, 1981 syn. n. and Youngulus Spangler, 1981
      syn. n., described at the genus rank, are placed in synonymy with Bidessodes.

PMID- 28435384
TI  - Two new species of Tipula (Vestiplex) from Southern China based on morphological
      and molecular data, with redescription of Tipula (Vestiplex) bicalcarata
      (Diptera, Tipulidae, Tipulinae).
AB  - Two new species of subgenus Tipula (Vestiplex) Bezzi, 1924, Tipula (Vestiplex)
      leigongshanensis Men & Young, sp. n. and Tipula (Vestiplex) maoershanensis Men &
      Young, sp. n. are described and illustrated. Tipula (Vestiplex) bicalcarata
      Savchenko, 1965 is redescribed and illustrated based on additional morphological
      characters. Partial mitochondrial cytochrome oxidase subunit I (COI) sequences of
      these three species are provided. Pairwise genetic distances among two new
      species and related species, Tipula (Vestiplex) bicalcarata, Tipula (Vestiplex)
      coxitalis Alexander, 1935, and Tipula (Vestiplex) sternotuberculata Alexander,
      1935 range from 0.028 to 0.091 using Kimura-2-parameter model. Diagnostic
      features of the sperm pump for taxonomic use are discussed.

PMID- 28435381
TI  - Complications in implant dentistry.
AB  - After tooth loss, an individual may seek tooth replacement so that his/her
      function and esthetics could be restored. Clinical prosthodontics, during the
      past decade, has significantly improved and developed according to the
      advancements in the science and patient's demands and needs. Conventional options
      in prosthodontics for substituting a missing single tooth include the removable
      partial denture, partial and full coverage bridgework, and resin-bonded
      bridgework. Dental implants have gained increasing popularity over the years as
      they are capable of restoring the function to near normal in both partial and
      completely edentulous arches. With substantial evidence available, fixed implant
      supported prosthesis are fully acknowledged as a reliable treatment option for
      the replacement of single or multiple missing teeth nowadays. While dental
      implants are increasingly becoming the choice of replacement for missing teeth,
      the impediments associated with them are progressively emerging too.

PMID- 28435385
TI  - A new species of Poropoea Foerster from Africa (Hymenoptera, Chalcidoidea,
      Trichogrammatidae).
AB  - A new species of Poropoea Foerster (Hymenoptera, Chalcidoidea, Trichogrammatidae)
      was obtained from eggs of attelabid beetles (Coleoptera: Attelabidae) associated
      with Combretum sp. (Myrtales, Combretaceae). This species is described from
      Ogooue-Ivindo province in north-eastern Gabon. The new species is easily
      distinguished from the known members of the genus Poropoea by the following
      combination of characters: female antennal club unsegmented, premarginal vein of
      the fore wing with a nodular premarginal vein and the stigma of the stigmal vein
      black, the wing lacks the RS1 track; front and hind legs more robust than the
      middle leg and with coxa and femur markedly enlarged, and ovipositor exserted to
      one-third of the gaster length. Morphological features of this new species are
      discussed and illustrated. A key to females of Poropoea species lacking the Rs1
      track in the fore wing has been constructed and is presented here.

PMID- 28435386
TI  - More new records of spider wasps from Colombia (Hymenoptera, Pompilidae).
AB  - Aporinellus Banks, Austrochares Banks and Dicranoplius Haupt are new generic
      records for Colombia, as well as the species Dipogon ariel Banks, Evagetes
      peruana Banks, and Euplaniceps notabilis (Smith). Five new combinations are
      formally endorsed: Aimatocare argentinica (Banks), comb. n.; Aimatocare longula
      (Banks), comb. n.; Aimatocare imitator (Evans), comb. n.; Aimatocare impensa
      (Evans), comb. n.; Aimatocare vitrea (Fox), comb. n. Although these names have
      been used in Pompilidae, no formal nomenclatural act had been proposed. The
      presence of Chirodamus paramicola Roig-Alsina, previously reported with
      uncertainty, is confirmed. Finally, a new combination for Euplaniceps notabilis
      (Smith), comb. n. is proposed based on molecular phylogenetics and morphological
      data. The Colombian fauna of Pompilidae sums up to 38 genera and approximately
      150 species.

PMID- 28435387
TI  - Larval morphology of Phratora koreana Takizawa, 1985 with a key to the larvae of
      the Palaearctic Phratora species (Coleoptera, Chrysomelidae, Chrysomelinae).
AB  - The first and third instar larvae of Phratora koreana Takizawa, 1985 are
      described and illustrated in detail for the first time. Morphological changes in
      the pigmentation, tubercular pattern and defensive glands during the larval
      development are discussed. The life cycle and host-plant of Phratora koreana and
      a key to the larvae of the Palaearctic Phratora species are also provided.

PMID- 28435388
TI  - Amphibians and reptiles of the state of Chihuahua, Mexico, with comparisons with
      adjoining states.
AB  - Chihuahua is Mexico's largest state, and its physiographic complexity affects the
      distribution of its herpetofauna. We list amphibians and reptiles for the state
      of Chihuahua, with their conservation status. We also compare this list to those
      of six adjoining states in the United States and Mexico (New Mexico, Texas,
      Coahuila, Durango, Sinaloa, and Sonora). A total of 175 species of amphibians and
      reptiles is found in Chihuahua. Thirty-eight are amphibians, and 137 reptiles.
      Chihuahuan amphibians and reptiles represent just over 37% of such species from
      Chihuahua and neighboring states. Chihuahua shares the highest proportion of its
      herpetofauna with Sonora and Durango. Most of the herpetofauna of Chihuahua falls
      in IUCNs least concern category and is not listed by SEMARNAT. However, turtles
      in Chihuahua are a group of particular conservation concern.

PMID- 28435389
TI  - Taxonomy of the Cryptopygus complex. II. Affinity of austral Cryptopygus s.s. and
      Folsomia, with the description of two new Folsomia species (Collembola,
      Isotomidae).
AB  - Folsomia minoraesp. n. and Folsomia australicasp. n. are described from New
      Zealand and Australia, respectively. Their possible affinity to two different
      groups of Cryptopygussensu stricto is discussed. Attention is paid to the
      variability of sensillary patterns of the genital segment in Cryptopygus: mainly,
      all s-chaetae are subequal, but in more advanced forms the dorsal triplet,
      lateral duplet or either of them become macrochaeta-like in length. Cryptopygus
      ulrikeae (= Folsomia ulrikeae Najt & Thibaud, 1987), comb. n. is given a new
      generic position.

PMID- 28435390
TI  - Synthesis and characterization of silver nanoparticles from (bis)alkylamine
      silver carboxylate precursors.
AB  - A comparative study of amine and silver carboxylate adducts [R1COOAg-2(R2NH2)]
      (R1 = 1, 7, 11; R2 = 8, 12) as a key intermediate in NPs synthesis is carried out
      via differential scanning calorimetry, solid-state FT-infrared spectroscopy, 13C
      CP MAS NMR, powder X-ray diffraction and X-ray photoelectron spectroscopy, and
      various solution NMR spectroscopies (1H and 13C NMR, pulsed field gradient spin
      echo NMR, and ROESY). It is proposed that carboxyl moieties in the presence of
      amine ligands are bound to silver ions via chelating bidentate type of
      coordination as opposed to bridging bidentate coordination of pure silver
      carboxylates resulting from the formation of dimeric units. All complexes are
      packed as lamellar bilayer structures. Silver carboxylate/amine complexes show
      one first-order melting transition. The evidence presented in this study shows
      that phase behavior of monovalent metal carboxylates are controlled, mainly, by
      head group bonding. In solution, insoluble silver salt is stabilized by amine
      molecules which exist in dynamic equilibrium. Using (bis)amine-silver carboxylate
      complex as precursor, silver nanoparticles were fabricated. During high
      temperature thermolysis, the (bis)amine-carboxylate adduct decomposes to produce
      silver nanoparticles of small size. NPs are stabilized by strongly interacting
      carboxylate and trace amounts of amine derived from the silver precursor
      interacting with carboxylic acid. A corresponding aliphatic amide obtained from
      silver precursor at high-temperature reaction conditions is not taking part in
      the stabilization. Combining NMR techniques with FTIR, it was possible to follow
      an original stabilization mechanism. Graphical abstractThe synthesis of a series
      (bis)alkylamine silver(I) carboxylate complexes in nonpolar solvents were carried
      out and fully characterized both in the solid and solution. Carboxyl moieties in
      the presence of amine ligands are bound to silver ions via chelating bidentate
      type of coordination. The complexes form layered structures which thermally
      decompose forming nanoparticles stabilized only by aliphatic carboxylates.

PMID- 28435391
TI  - Programmed cell death 1 checkpoint inhibitors in the treatment of patients with
      advanced melanoma.
AB  - The treatment landscape of advanced melanoma has changed significantly following
      the discovery and marketing authorisation of immune checkpoints inhibitors.
      Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated
      long-term survival in about 20% of patients. Subsequently, anti-programmed cell
      death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD
      1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy
      with lower toxicity comparing to ipilimumab. The highest clinical benefit in
      patients was observed when nivolumab and ipiliumumab were combined. However, the
      above strategy, due to very high toxicity, has limitations for use in all
      patients with advanced melanoma. Notwithstanding, patients treated with anti-PD1
      beyond disease progression benefit from treatment continuation; further studies
      are warranted in this indication. Furthermore, patients responding to treatment
      with anti-PD1 will benefit from the therapy after its discontinuation. Immune
      checkpoint inhibitors are clinically effective regardless of BRAF mutation.
      Currently there is no recommendation regarding which treatment option should be
      selected for the treatment of the population - immunotherapy or targeted therapy
      with BRAF and MEK inhibitors. Randomised trials are ongoing comparing these two
      treatment strategies in patients with BRAF mutation. Encouraging results were
      observed in early phase trials in patients receiving the combination of immune
      and targeted therapy. Phase 3 studies are underway. Patients with elevated serum
      lactate dehydrogenase present poor prognosis regardless of the systemic treatment
      used. novel treatment strategies should probably be developed for these patients.

PMID- 28435392
TI  - A systemic literature review of neuroimaging studies in women with breast cancer
      treated with adjuvant chemotherapy.
AB  - Chemotherapy-induced cognitive deficits in patients with breast cancer,
      predominantly in attention and verbal memory, have been observed in numerous
      studies. These neuropsychological findings are corroborated by the results of
      neuroimaging studies. The aim of this paper was to survey the reports on cerebral
      structural and functional alterations in women with breast cancer treated with
      chemotherapy (CTx). First, we discuss the host-related and disease-related
      mechanisms underlying cognitive impairment after CTx. We point out the direct and
      indirect neurotoxic effect of cytostatics, which may cause: a damage to neurons
      or glial cells, changes in neurotransmitter levels, deregulation of the immune
      system and/or cytokine release. Second, we focus on the results of neuroimaging
      studies on brain structure and function that revealed decreased: density of grey
      matter, integrity of white matter and volume of multiple brain regions, as well
      as their lower activation during cognitive task performance. Finally, we
      concentrate on compensatory mechanisms, which activate additional brain areas or
      neural connection to reach the premorbid cognitive efficiency.

PMID- 28435394
TI  - The role of mast cells in oral squamous cell carcinoma.
AB  - The mast cells are initial effective lineage in both humoral and adaptive
      immunity. They are ubiquitous in skin, mucosa, and in function. They contain
      biologically essential and dynamic mediators in healthy and harmful conditions of
      tissue. Mast cell malfunctioning could be attributed to various chronic allergic
      diseases. Considerately, emerging evidence of mast cell involvement in various
      cancers shows them to have both positive and negative roles in tumour growth. It
      mostly indulges in tumour progression and metastasis via angiogenesis,
      extracellular matrix degradation, and mitogenic activity in the tumour
      microenvironment. The current paper reviewed research papers on mast cells in
      oral squamous cell carcinoma through the PubMed database from 1980 to the present
      date. The present paper is an attempt to summarise the research reports on the
      role of mast cells in oral squamous cell carcinoma. Further to this note, this
      paper also outlines the role of mast cells in normal physiological processes and
      tumour biology.

PMID- 28435393
TI  - S-1 for treatment of advanced hepatocellular carcinoma: a systematic review of
      the literature.
AB  - Hepatocellular carcinoma (HCC) is the most common liver neoplasm worldwide. Based
      on its potent inhibition of dihydropyrimidine dehydrogenase (DPD), S-1 is
      expected to be more active than other fluoropyrimidines against HCC with DPD
      activity. This systematic review was aimed to assess the efficacy and safety of S
      1 for treatment of advanced HCC. PubMed, the Cochrane Library, EMBA-SE, and
      ClinicalTrials.gov were searched using the terms "Hepatocellular Carcinoma" or
      "HCC" or "Hepatoma" or "Liver cancer" and ''S-1''. Outcomes of main interest
      included overall survival (OS) and toxicities. We identified four studies of S-1
      treatment alone from 1059 references, including a total of 272 patients. There
      were two original articles and two conference abstracts. The percentage of male
      patients ranged from 88 to 91.3% and median age ranged from 59 to 70 years.
      Median OS ranged from 8.6 to 16.5 months. The incidences of toxicity of more than
      50% were thrombocytopaenia and fatigue. According to the original description,
      toxicities were acceptable. The current evidence from the available clinical
      studies suggests that S-1 may be an effective and tolerable treatment for
      advanced HCC. Further clinical studies are warranted to further investigate this
      treatment option.

PMID- 28435395
TI  - Prevention of pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDA) accounts for 95% of all pancreatic
      cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the
      lowest five-year survival rate as compared to others cancers. PDA in Poland is
      the fifth leading cause of death after lung, stomach, colon and breast cancer. In
      our paper we have analysed the newest epidemiological research, some of it
      controversial, to establish the best practical solution for pancreatic cancer
      prevention in the healthy population as well as treatment for patients already
      diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but
      is usually diagnosed too late, at its advanced stage. Screening for PDA is not
      very well defined except in subgroups of high-risk individuals with genetic
      disorders or with chronic pancreatitis. We present convincing, probable, and
      suggestive risk factors associated with pancreatic cancer, many of which are
      modifiable and should be introduced and implemented in our society.

PMID- 28435396
TI  - Lentivirus-mediated knockdown of P27RF-Rho inhibits hepatocellular carcinoma cell
      growth.
AB  - AIM OF THE STUDY: To investigate the effects of P27RF-Rho on hepatocellular
      carcinoma (HCC) cell growth and explore the possibility of using it as a novel
      therapeutic target for liver cancer treatment. MATERIAL AND METHODS: P27RF-Rho in
      HCC cells was silenced by lentivirus-mediated RNA interference, and the silencing
      effect was verified by RT-PCR. Cell proliferation was determined by MTT and clone
      formation assay. Cell cycle phase and apoptosis were detected through FACS. The
      expression level of cell growth, apoptosis, and metastasis associated genes was
      detected by quantitative PCR. RESULTS: Lentivirus-mediated P27RF-Rho knockdown
      inhibited HCC cell growth and clone formation. P27RF-Rho silence induced cell
      cycle arrest and apoptosis. The mRNA level of genes associated with cell cycle,
      apoptosis, and invasion also significantly altered after P27RF-Rho knockdown.
      Cyclin A, CDK2, BCL-2, and MMP-9 were down-regulated. P27 and Bax were up
      regulated. CONCLUSIONS: P27RF-Rho knockdown inhibits HCC cell growth, and P27RF
      Rho is probably a promising target for HCC treatment.

PMID- 28435397
TI  - Leptin receptor Q223R polymorphism in Egyptian female patients with breast
      cancer.
AB  - AIM OF THE STUDY: Breast cancer is the most common cause of death in women.
      Obesity has been associated with increased risk of breast cancer in post
      menopausal women. It induces chronic inflammation, which increases local and
      systemic levels of cytokines and adipokines such as leptin. Leptin (LEP) and
      leptin receptor (LEPR) genes have several polymorphisms in humans. This study
      aims to assess the association between blood levels of leptin and LEPR Q223R gene
      polymorphism in patients of cancer breast. MATERIAL AND METHODS: The current
      study was carried on 48 female breast cancer patients and 48 heathy female
      subjects. Carcinoembryonic antigen (CEA), cancer antibody CA15-3, and leptin
      hormone were determined. Single nucleotide polymorphism of LEPR Q223R was
      assessed by PCR/RFLP. Statistical analysis used: The statistical analysis of data
      was done by using SPSS version 20. RESULTS: There were significant increases in
      the concentrations of CEA (p = 0.004), CA15-3 (p < 0.001), and leptin hormone (p
      < 0.001) in BC patients in relation to the respective concentrations in control
      subjects. CEA and CA 15-3 showed significant differences between various BC
      stages. As regard to LEPR Q223R gene polymorphism, AA genotype showed
      significantly higher frequency in BC patients when compared to their respective
      controls, with higher risk to develop BC. CONCLUSIONS: Leptin hormone shows
      significantly higher concentrations in BC patients. As regard to LEPR Q223R gene
      polymorphism, AA genotype showed significantly higher frequency in BC patients.

PMID- 28435398
TI  - The changes of tumour vascular endothelial growth factor expression after
      neoadjuvant chemoradiation in patients with rectal adenocarcinoma.
AB  - AIM OF THE STUDY: The aim was to examine the effects of neoadjuvant
      chemoradiotherapy on VEGF expression in patients with locally advanced rectal
      cancer. MATERIALS AND METHODS: A total of 53 patients with locally advanced
      rectal cancer were retrospectively studied. Neoadjuvant treatment comprised
      external beam radiation (50.4 Gy/28 fractions) with continuous infusion of 5
      fluorouracil. Four to 6 weeks after the chemoradiotherapy, the patients underwent
      surgical resection. Immunohistochemistry was performed to assess VEGF expression
      in the pretreatment biopsies and in resected specimens. RESULTS: Resection with
      microscopic residual tumour (R1) was performed in two patients while in the
      remaining 51 patients radical resection with microscopically negative margins
      (R0) was possible. Downstaging after preoperative chemoradiotherapy was observed
      in 34 patients (64%). After chemoradiotherapy 24 patients (45%) had decreased
      VEGF expression, in 20 patients (38%) there was no change, and in two patients it
      was not possible to assess the dynamics of VEGF expression due to pathologic
      complete response after chemoradiotherapy. The five-year overall survival (OS)
      rate was 56% (95% CI: 43-70%). Although the median OS was 2.5 times shorter in
      patients who experienced decreased VEGF expression during therapy, this
      difference did not reach statistical significance. VEGF expression was not
      significant in Cox regression analysis or log-rank test. VEGF expression
      decreased after neoadjuvant chemoradiotherapy in most patients with rectal
      adenocarcinoma examined. This decrease was associated with a trend of inferior
      prognosis. CONCLUSIONS: VEGF expression decreased after neoadjuvant
      chemoradiotherapy in most patients examined. This decrease was associated with a
      trend of inferior prognosis.

PMID- 28435399
TI  - Serum atrial natriuretic peptide: a suspected biomarker of breast cancer.
AB  - AIM OF THE STUDY: To assess serum levels of ANP in breast cancer female patients
      and its relationship to metastasis and some clinical parameters among those
      patients. MATERIAL AND METHODS: One hundred breast cancer patients with and
      without metastasis along with 20 healthy closely matched controls, were enrolled
      in the present cross sectional study. Background: To assess the serum levels of
      atrial natriuretic peptide in breast cancer Serum levels of ANP were assessed
      using ELISA. RESULTS: Mean serum levels of ANP breast cancer patients (13.9 +/
      10.1 ng/ml) were significantly elevated compared to healthy control group (2.2 +/
      1.3 ng/ml) (p < 0.001). The metastatic breast cancer patients showed significant
      elevated ANP levels (17.1 +/-8.9 ng/ml) compared to non-metastatic group (6.4 +/
      8.8 ng/ml) p < 0.001. Within the metastatic group significant difference was
      detected between de novo metastatic, under follow-up, under hormonal control and
      locally advanced group (p = 0.007). CONCLUSIONS: This study showed significant
      elevated levels of ANP in the serum of metastatic breast cancer patients compared
      to non-metastatic patients. Within the metastatic group the lowest levels were
      detected in metastatic breast Cancer under hormonal treatment either tamoxifen or
      aromatase inhibitor.

PMID- 28435400
TI  - Neoadjuvant sequential chemoradiotherapy versus radiotherapy alone for treatment
      of high-risk extremity soft tissue sarcoma: a single-institution experience.
AB  - AIM OF THE STUDY: Patients with large and high-grade extremity soft-tissue
      sarcoma are at significant risk for distant metastasis and sarcoma-related death.
      There is no randomized trial comparing chemoradiotherapy to radiotherapy in the
      neoadjuvant setting for high risk extremity soft-tissue sarcoma. The aim of this
      study is to evaluate the outcomes of patients treated with two different
      modalities (neoadjuvant sequential chemoradiotherapy vs. radiotherapy alone) in a
      single center. MATERIAL AND METHODS: Data of 67 patients were analyzed
      retrospectively. Thirty-four patients received neoadjuvant sequential
      chemoradiotherapy (2-3 cycles of doxorubicin (75 mg/m2) and ifosfamide (6 g/m2)
      followed by radiotherapy of 28 Grays (Gy) administered as 8 fractions of 35 Gy)
      and 33 patients received radiotherapy alone. R0 resection rates and 3-year
      survival estimates were evaluated. RESULTS: Median follow-up time was 37 months.
      The estimated 3-year overall and disease-free survival rates for the whole
      patient group were 79% (95% CI: 67.0-86.4) and 57.9% (95% CI: 46.3-69.0),
      respectively. The most common side effects were nausea and leucopenia. Three-year
      overall, disease-free, local recurrence-free and distant recurrence-free survival
      rates did not differ significantly. All patients except one underwent wide
      excision or compartmental resection. R0 resection rate for the whole patient
      group was 92.5% (n = 62). Sites of progression were similar across both treatment
      arms. CONCLUSIONS: Preoperative hypofractionated radiotherapy alone or
      sequentially with chemotherapy result in high rates of limb salvage and
      acceptable toxicity. Our study results did not show a statistically significant
      treatment effect regarding survival and patterns of failure.

PMID- 28435401
TI  - Head and neck lymphomas - a retrospective ten-year observation.
AB  - AIM OF THE STUDY: Lymphomas are a heterogeneous group of tumours of lymphoid
      tissue in which there is an abnormal proliferation of cells of the lymphatic
      system. The literature notes a gradual increase in the incidence of this type of
      cancer in the whole population. The aim of the study was to evaluate whether the
      above tendency occurs in the head and neck area. MATERIAL AND METHODS: In the
      years 2005-2014, at the Otolaryngology and Laryngological Oncology Department of
      the Upper Silesian Medical Centre in Katowice, 77 cases of lymphoma were
      recorded, 58 of which were analysed in terms of location, histological type, age
      and sex of the patient, and the presence of risk factors. RESULTS: The vast
      majority of them were non-Hodgkin's lymphomas (NHL) - 67.53%. Hodgkin's lymphomas
      (HL) accounted for only a small fraction of diagnoses (7.79%). In terms of
      histopathological types, in most cases of NHL, there occurred diffuse large B
      cell lymphomas (DLBCL) - 51.92%. The most common location was the lymph nodes,
      representing the location of the primary lesion in more than half of the cases.
      As regards the extranodal location, the Waldeyer ring dominated (54.54%) along
      with the palatal tonsil (40.90%). There has been a significant upward trend,
      especially in the incidence of NHL.

PMID- 28435403
TI  - Comparative analysis of the incidence of head and neck cancer in south-eastern
      Poland and in Poland in the years 1990-2012.
AB  - AIM OF THE STUDY: To present the changes in the incidence of cancers of the head
      and neck organs in south-eastern Poland and in the whole country in the years
      1990-2012. MATERIAL AND METHODS: A retrospective analysis the incidence of
      cancers of the head and neck organs in south-eastern Poland in the years 1990
      2012. Statistical methods used for cancers of ICD-10 C00-C14 and C30-C32.
      RESULTS: For Poland, the absolute number of cases was 123,120 in the years 1990
      2012. For males, the number of cases per year increased from 4468 in 1990 to 4953
      in 2012, and for females from 816 to 1442. The percentage share of tumours of the
      head and neck in all malignant tumours decreased from 10.0% to 6.5% for males and
      from 2.1% to 1.9% for females. In the years 1990-2012 in south-eastern Poland,
      for males, the absolute number of cases per year decreased from 335 in 1990 to
      286 in 2012. For females, a minimal increase in cases was from 63 to 64 cases.
      The percentage share of tumours of the head and neck in all malignant tumours
      decreased from 12.2% to 6.7% for males and from 2.7% to 1.8% for females.
      CONCLUSIONS: Incidences of cancers of the head and neck organs in Poland have
      seen a slight upward trend in the absolute number of cases over the last two
      decades. In Poland a decrease in the incidence of cancer of the larynx was
      reported, with an increase in the incidence of oropharyngeal cancer.

PMID- 28435402
TI  - Synchronous bilateral testis cancer: clinical and oncological management.
AB  - Synchronous bilateral testis cancer (SBTC) is a rare event. It represents only
      0.5-1% of all new cases of testicular cancer. Patients with this disease require
      careful management for psychological, oncological, and medical problems. We
      performed a PubMed search for all series that reported SBTC. We considered only
      articles in English, reporting on more than three cases. We also performed an
      analysis of the reported evidence regarding testosterone replacement and surgical
      treatment. We found 10 studies satisfying inclusion criteria for a total of 73
      patients. The majority are bilateral seminoma, which present with a low stage at
      diagnosis, and mixed histology tumours, both with a good overall survival. On the
      other hand, cases with bilateral non-seminoma histology are associated with poor
      prognosis and high stage at presentation. Testis-sparing surgery should be an
      eligible choice in selected cases, to preserve fertility and avoid testosterone
      deficiency. Multiple biopsies are recommended in these patients, and in the case
      of intratubular germ cell neoplasia (ITGCN) presence, scrotal radiotherapy is
      mandatory. Subcutaneous testosterone pellets guarantee higher patient acceptance
      and physiological testosterone levels. Lifelong follow-up and psychological
      support, with special care for infertility and erectile dysfunction, must be
      considered in this cohort of patients.

PMID- 28435404
TI  - Phase II study of adjuvant docetaxel and carboplatin with/without doxorubicin and
      cyclophosphamide in triple negative breast cancer: a randomised controlled
      clinical trial.
AB  - AIM OF THE STUDY: The aim of this trial was to compare overall survival (OS),
      disease-free survival (DFS), and toxicity of two adjuvant regimens in triple
      negative patients with Iranian ethnicity. MATERIAL AND METHODS: In a phase II
      trial, patients with previously untreated triple negative breaststroke cancer
      were randomly assigned by using docetaxel 70 mg/m2 and carboplatin AUC = 7 every
      three weeks with granulocyte colony-stimulating factor for sin courses (arm A) or
      doxorubicin hydrochloride 60 mg/m2 and cyclophosphamide 600 mg/m2 every three
      weeks with G-CSF for four courses followed by docetaxel 70 mg/m2 and carboplatin
      AUC = 7 every three weeks with G-CSF for four courses (arm B). RESULTS: A total
      of 119 patients were randomly enrolled in our study (60 patients in Arm A and 59
      patients in Arm B) between 2011 and 2016. The mean follow-up was 40 months at the
      time of treatment analysis. The 2-year and 5-year DFS rates for Arm A were 92.7%
      vs. 85% and for Arm B were 82.6% vs. 64.4%. The 2-year and 5-year OS rates for
      Arm A were 96.5% vs. 91.7% and for Arm B were 90.5% vs. 81.3%. There was a
      significant correlation for DFS and OS in the two arms. There was no significant
      difference between adverse events with the two regimens. CONCLUSIONS: In our
      research, less progression was found with Arm A as compared to Arm B. Adding of
      anthracyclines such as doxorubicin hydrochloride did not increase OS and DFS in
      triple negative breast cancer (TNBC) patients.

PMID- 28435406
TI  - Treating the Whole Patient.

PMID- 28435405
TI  - Establishment and characterization of 6 novel patient-derived primary pancreatic
      ductal adenocarcinoma cell lines from Korean pancreatic cancer patients.
AB  - BACKGROUND: Pancreatic ductal adenocarcinomas are among the most malignant
      neoplasms and have very poor prognosis. Our understanding of various cancers has
      recently improved the survival of patients with cancer, except for pancreatic
      cancers. Establishment of primary cancer cell lines of pancreatic ductal
      adenocarcinomas will be useful for understanding the molecular mechanisms of this
      disease. METHODS: Eighty-one surgically resected pancreatic ductal
      adenocarcinomas were collected. Six novel pancreatic cancer cell lines, AMCPAC01
      06, were established and histogenetic characteristics were compared with their
      matched tissues. The clinicopathologic and molecular characteristics of the cell
      lines were investigated by KRAS and TP53 sequencing or SMAD4 and p53
      immunohistochemistry. Xenografts using AMCPAC cell lines were established.
      RESULTS: From the 81 pancreatic ductal adenocarcinomas, six (7.4% success rate)
      patient-derived primary cell lines were established. The six AMCPAC cell lines
      showed various morphologies and exhibited a wide range of doubling times. AMCPAC
      cell lines contained mutant KRAS in codons 12, 13, or 61 and TP53 in exon 5 as
      well as showed aberrant p53 (5 overexpression and 1 total loss) or DPC4 (all 6
      intact) expression. AMCPAC cell lines demonstrated homology for the KRAS mutation
      and p53 expression compared with matched primary cancer tissues, but showed
      heterogeneous DPC4 expression patterns. CONCLUSIONS: The novel AMCPAC01-06 cell
      lines established in this study may contribute to the understanding of pancreatic
      ductal adenocarcinomas. Trial registration Retrospectively registered.

PMID- 28435410
TI  - Proton Pump Inhibitor-Responsive Esophageal Eosinophilia.

PMID- 28435411
TI  - Surveillance for Hepatocellular Carcinoma.

PMID- 28435407
TI  - Hepatitis C Virus Treatment in HIV-Coinfected Patients: No Longer Different From
      Monoinfection Treatment.
AB  - Between 15% and 30% of patients infected with HIV in the United States and Europe
      are coinfected with hepatitis C virus (HCV), and rates of acute HCV infection
      have been increasing in some populations of HIV-positive patients. Liver disease
      is now a leading cause of death in HIV-infected patients. Patients with HIV/HCV
      coinfection have lower rates of spontaneous acute HCV clearance, poorer response
      to treatment of chronic HCV in the pre-direct-acting antiviral era, more rapid
      progression to cirrhosis, and increased risk of hepatocellular carcinoma. This
      article will summarize data on management of HIV/HCV coinfection, discuss the
      epidemic of acute HCV infection in HIV-infected patients, and examine the many
      new HCV treatment regimens on the horizon with data on coinfected patients.

PMID- 28435409
TI  - Insight Into the Relationship Between Gastroesophageal Reflux Disease and Asthma.
AB  - Gastroesophageal reflux disease (GERD) is a common condition that presents with
      symptoms of heartburn and regurgitation. Asthma is an equally common medical
      condition that often coexists with GERD. The clinical scenario of difficult-to
      treat asthma in the setting of concomitant GERD leads to the possibility of GERD
      induced asthma. However, asthma may also induce GERD, so confusion has developed
      about the role of GERD in patients with moderate to severe asthma. Acid
      suppressive therapy may be initiated in patients with asthma, but controlled
      studies have recently questioned the role of such therapy and, thus, have caused
      further confusion in this field. Recent advancements in the field of esophageal
      physiologic testing in GERD have introduced the concept of impedance-pH
      monitoring, which suggests a possible role of nonacid reflux in those who
      continue to be symptomatic despite acid-suppressive therapy. However, recent data
      caution about the role of surgical fundoplication based solely on the results of
      impedance monitoring. This article reviews current knowledge in the fields of
      GERD and asthma and suggests a possible treatment option for this group of
      patients.

PMID- 28435408
TI  - Clinical Review of Small-Bowel Endoscopic Imaging.
AB  - Endoscopic imaging of the small bowel, frequently used in gastroenterology
      practice, encompasses mainly video capsule endoscopy (VCE) and device-assisted
      enteroscopy (DAE). Both tests are essential diagnostic tools to evaluate obscure
      gastrointestinal bleeding and suspected small-bowel disorders, such as Crohn's
      disease. VCE solely identifies and localizes small-bowel pathology, whereas DAE
      offers both visualization and tissue sampling to diagnose diseased structures and
      perform therapeutic maneuvers, such as those needed to achieve hemostasis. In
      this context, VCE is frequently used as a screening test for small-bowel
      abnormalities that, when present, are then managed with DAE.

PMID- 28435412
TI  - Sleep and Inflammatory Bowel Disease.

PMID- 28435413
TI  - ERCP and Mortality.

PMID- 28435414
TI  - Nearest neighbor imputation using spatial-temporal correlations in wireless
      sensor networks.
AB  - Missing data is common in Wireless Sensor Networks (WSNs), especially with multi
      hop communications. There are many reasons for this phenomenon, such as unstable
      wireless communications, synchronization issues, and unreliable sensors.
      Unfortunately, missing data creates a number of problems for WSNs. First, since
      most sensor nodes in the network are battery-powered, it is too expensive to have
      the nodes retransmit missing data across the network. Data re-transmission may
      also cause time delays when detecting abnormal changes in an environment.
      Furthermore, localized reasoning techniques on sensor nodes (such as machine
      learning algorithms to classify states of the environment) are generally not
      robust enough to handle missing data. Since sensor data collected by a WSN is
      generally correlated in time and space, we illustrate how replacing missing
      sensor values with spatially and temporally correlated sensor values can
      significantly improve the network's performance. However, our studies show that
      it is important to determine which nodes are spatially and temporally correlated
      with each other. Simple techniques based on Euclidean distance are not sufficient
      for complex environmental deployments. Thus, we have developed a novel Nearest
      Neighbor (NN) imputation method that estimates missing data in WSNs by learning
      spatial and temporal correlations between sensor nodes. To improve the search
      time, we utilize a kd-tree data structure, which is a non-parametric, data-driven
      binary search tree. Instead of using traditional mean and variance of each
      dimension for kd-tree construction, and Euclidean distance for kd-tree search, we
      use weighted variances and weighted Euclidean distances based on measured
      percentages of missing data. We have evaluated this approach through experiments
      on sensor data from a volcano dataset collected by a network of Crossbow motes,
      as well as experiments using sensor data from a highway traffic monitoring
      application. Our experimental results show that our proposed ??-NN imputation
      method has a competitive accuracy with state-of-the-art Expectation-Maximization
      (EM) techniques, while using much simpler computational techniques, thus making
      it suitable for use in resource-constrained WSNs.

PMID- 28435415
TI  - The Gold Coast Integrated Care Model.
AB  - This article outlines the development of the Australian Gold Coast Integrated
      Care Model based on the elements identified in contemporary research literature
      as essential for successful integration of care between primary care, and acute
      hospital services. The objectives of the model are to proactively manage high
      risk patients with complex and chronic conditions in collaboration with General
      Practitioners to ultimately reduce presentations to the health service emergency
      department, improve the capacity of specialist outpatients, and decrease planned
      and unplanned admission rates. Central to the model is a shared care record which
      is maintained and accessed by staff in the Coordination Centre. We provide a
      process map outlining the care protocols from initial assessment to care of the
      patient presenting for emergency care. The model is being evaluated over a pilot
      three year proof of concept phase to determine economic and process perspectives.
      If found to be cost-effective, acceptable to patients and professionals and as
      good as or better than usual care in terms of outcomes, the strategic intent is
      to scale the programme beyond the local health service.

PMID- 28435416
TI  - Challenges in Achieving Collaboration in Clinical Practice: The Case of Norwegian
      Health Care.
AB  - INTRODUCTION: This article summarizes and synthesizes the findings of four
      separate but inter-linked empirical projects which explored challenges of
      collaboration in the Norwegian health system from the perspectives of providers
      and patients. The results of the four projects are summarised in eight articles.
      METHODS: The eight articles constituted our empirical material. Meta-ethnography
      was used as a method to integrate, translate, and synthesize the themes and
      concepts contained in the articles in order to understand how challenges related
      to collaboration impact on clinical work. RESULTS: Providers' collaboration
      across all contexts was hampered by organizational and individual factors,
      including, differences in professional power, knowledge bases, and professional
      culture. The lack of appropriate collaboration between providers impeded clinical
      work. Mental health service users experienced fragmented services leading to
      insecurity and frustration. The lack of collaboration resulted in inadequate
      rehabilitation services and lengthened the institutional stay for older patients.
      CONCLUSION: Focusing on the different perspectives and the inequality in power
      between patients and healthcare providers and between different providers might
      contribute to a better environment for achieving appropriate collaboration.
      Organizational systems need to be redesigned to better nurture collaborative
      relationships and information sharing and support integrated working between
      providers, health care professionals and patients.

PMID- 28435417
TI  - The Evolution of an Interprofessional Shared Decision-Making Research Program:
      Reflective Case Study of an Emerging Paradigm.
AB  - INTRODUCTION: Healthcare research increasingly focuses on interprofessional
      collaboration and on shared decision making, but knowledge gaps remain about
      effective strategies for implementing interprofessional collaboration and shared
      decision-making together in clinical practice. We used Kuhn's theory of
      scientific revolutions to reflect on how an integrated interprofessional shared
      decision-making approach was developed and implemented over time. METHODS: In
      2007, an interdisciplinary team initiated a new research program to promote the
      implementation of an interprofessional shared decision-making approach in
      clinical settings. For this reflective case study, two new team members analyzed
      the team's four projects, six research publications, one unpublished and two
      published protocols and organized them into recognizable phases according to
      Kuhn's theory. RESULTS: The merging of two young disciplines led to challenges
      characteristic of emerging paradigms. Implementation of interprofessional shared
      decision making was hindered by a lack of conceptual clarity, a dearth of
      theories and models, little methodological guidance, and insufficient evaluation
      instruments. The team developed a new model, identified new tools, and engaged
      knowledge users in a theory-based approach to implementation. However, several
      unresolved challenges remain. DISCUSSION: This reflective case study sheds light
      on the evolution of interdisciplinary team science. It offers new approaches to
      implementing emerging knowledge in the clinical context.

PMID- 28435418
TI  - "You Never Know What Happens Next" - Young Adult Service Users' Experience with
      Mental Health Care and Treatment through One Year.
AB  - Fragmented services are a well-known problem in the mental health sector. Mental
      health service users' experiences of treatment and care can provide knowledge for
      developing more user-oriented continuity of care. We followed nine young adults
      with mental health illnesses and complex needs, conducting four interviews with
      each informant in the course of a year. The aim was to capture their experiences
      and views about treatment and care, focusing on (dis)continuities and episodes
      occurring through that year. The users' experiences were affected by shifts and
      transitions between institutions, units and practitioners while their need was
      predictability and stability. A good and stable patient-provider relationship was
      considered highly useful but difficult to establish. The participants had a
      strong desire for explanation, adequate treatment and progress, but very
      different perceptions of the usefulness of diagnoses. Some felt rejected when
      they tried to tell the therapist about their trauma. Lack of user-involvement
      characterized many of the participants' stories while they desired to become more
      engaged and included in important decisions concerning treatment and medication.
      The participants' experiences stand in contrast to key policy goals of coherent
      mental health services. The article discusses what may explain the gap between
      policy and reality, and how continuity of care may be improved.

PMID- 28435419
TI  - The Process of Creating Integrated Home Care in Lithuania: from Idea to Reality.
AB  - BACKGROUND: The article presents an analysis of the formulation and
      implementation of a social innovation: integrated home care (IHC) in post-soviet
      Lithuania. From 1998 a series of top-down orders to implement IHC were issued,
      however, home nursing did not start. In 2011 the Ministry of Social Security and
      Labour began a process to develop integrated home care using new, collaborative
      processes. The result was 21 pilot projects with well-conceptualized IHC
      services. METHOD: Using data from focus groups, interviews, and recorded
      observations, the research team systematically documented the innovation process,
      including themes and deviations, employing Smale's Innovation Trinity framework
      to organize the larger picture. RESULTS: In the Lithuanian post-totalitarian
      context, top-down communication was found to be prevalent. Not only IHC, but also
      openness to change and dialogue at high levels were innovations. Patient-centered
      practice at local levels could only occur when a new attitude of mind was reached
      through dialogue with officials at higher levels and between peers. CONCLUSIONS:
      The enactment, rather than the mask of dialogue, participatory program
      development were critical in the success of IHC innovation. This is difficult to
      achieve in the light of antiquated public bureaucracies, but in this case, the
      Ministry team, rather than avoiding the expectation of top-down communication,
      made it into an asset through promotion of collaboration.

PMID- 28435420
TI  - Qualitative Evaluation of the Implementation of an Integrated Care Delivery Model
      for Chronic Patients with Multi-Morbidity in the Basque Country.
AB  - INTRODUCTION: The objective of this study was to assess a model for improving
      healthcare integration for patients with multiple chronic diseases in an
      integrated healthcare organisation in the Basque Country and to propose areas for
      improvement. METHODS: We organised four nominal groups composed of
      representatives from different categories of clinicians involved in the
      development of an integrated healthcare organisation and in the integrated care
      of patients with multiple diseases, namely, internists, general practitioners,
      and primary care and hospital nurses. RESULTS: The aspect rated most positively
      was the concept itself of an integrated care model, which is able to improve
      communication between levels of care, increase the quality of the care provided
      and enhance patient safety. Additionally, it was agreed that the role of assigned
      clinicians is a key element. The problems identified mostly concern its
      implementation in daily practice. CONCLUSIONS: The results of this study made it
      possible to suggest at least 8 areas of improvement to be implemented. These are
      related to: nurses' roles; care and monitoring of stable patients; team work;
      communication with patients; coordination with social workers and between
      internists and family doctors; as well as the development of an office of medical
      services to lead the integration process.

PMID- 28435421
TI  - Translating the Patient Perception of Integrated Care Survey to Measure
      Integrated Care in the Netherlands: Combining Equivalence and Contextualization
      Approaches for Optimal Results.
AB  - INTRODUCTION: An increase in initiatives to improve integration of care provides
      the need for instruments that assess the degree of integrated care as perceived
      by patients across cultural contexts. This article aims to explain the relevance
      of equivalence and contextualization approaches in translating and adapting the
      Patient Perception of Integrated Care Survey developed in the US for use in the
      Netherlands. THEORY AND METHODS: The World Health Organization guidelines guided
      the translation and adaptation, including a forward-backward translation and
      patient-feedback through informal contacts (N4) and cognitive interviews (N14).
      RESULTS: The forward-backward translation produced a Dutch version of the Patient
      Perception of Integrated Care Survey with minor adaptations. Patients evaluated
      the survey as very relevant. Alterations resulted from structural and cultural
      differences and specificities of patients with chronic conditions. CONCLUSIONS
      AND DISCUSSION: A context-sensitive translation process is key to developing
      instruments for cross-cultural health research. Our results show that equivalence
      and contextualization methods provide equally relevant, yet substantially
      different contributions to the translation outcome and should both be
      incorporated when translating instruments for different cultural contexts. The
      results support the applicability of the Patient Perception of Integrated Care
      Survey in the Netherlands and are promising for its adoption in other cultural
      contexts.

PMID- 28435422
TI  - Development and Validation of an Instrument for Assessing Patient Experience of
      Chronic Illness Care.
AB  - INTRODUCTION: The experience of chronic patients with the care they receive,
      fuelled by the focus on patient-centeredness and the increasing evidence on its
      positive relation with other dimensions of quality, is being acknowledged as a
      key element in improving the quality of care. There are a dearth of accepted
      tools and metrics to assess patient experience from the patient's perspective
      that have been adapted to the new chronic care context: continued, systemic, with
      multidisciplinary teams and new technologies. METHODS: Development and validation
      of a scale conducting a literature review, expert panel, pilot and field studies
      with 356 chronic primary care patients, to assess content and face validities and
      reliability. RESULTS: IEXPAC is an 11+1 item scale with adequate metric
      properties measured by Alpha Chronbach, Goodness of fit index, and satisfactory
      convergence validity around three factors named: productive interactions, new
      relational model and person's self-management. CONCLUSIONS: IEXPAC allows
      measurement of the patient experience of chronic illness care. Together with
      other indicators, IEXPAC can determine the quality of care provided according to
      the Triple Aim framework, facilitating health systems reorientation towards
      integrated patient-centred care.

PMID- 28435424
TI  - Stepped Care, System Architecture and Mental Health Services in Australia.

PMID- 28435423
TI  - Quality of Care and Job Satisfaction in the European Home Care Setting: Research
      Protocol.
AB  - INTRODUCTION: Since the European population is ageing, a growing number of
      elderly will need home care. Consequently, high quality home care for the elderly
      remains an important challenge. Job satisfaction among care professionals is
      regarded as an important aspect of the quality of home care. AIM: This paper
      describes a research protocol to identify elements that have an impact on job
      satisfaction among care professionals and on quality of care for older people in
      the home care setting of six European countries. METHODS: Data on elements at the
      macro-level (policy), meso-level (care organisations) and micro-level (clients)
      are of importance in determining job satisfaction and quality of care. Macro
      level indicators will be identified in a previously published literature review.
      At meso- and micro-level, data will be collected by means of two questionnaires
      utilsed with both care organisations and care professionals, and by means of
      interRAI Home Care assessments of clients. The client assessments will be used to
      calculate quality of care indicators. Subsequently, data will be analysed by
      means of linear and stepwise multiple regression analyses, correlations and
      multilevel techniques. CONCLUSIONS AND DISCUSSION: These results can guide health
      care policy makers in their decision making process in order to increase the
      quality of home care in their organisation, in their country or in Europe.

PMID- 28435426
TI  - Measuring Integrated Care - The Quest for Disentangling a Gordian Knot.

PMID- 28435425
TI  - Power and Integrated Health Care: Shifting from Governance to Governmentality.
AB  - Integrated care occurs within micro, meso and macro levels of governance
      structures, which are shaped by complex power dynamics. Yet theoretically-led
      notions of power, and scrutiny of its meanings and its functioning, are neglected
      in the literature on integrated care. We explore an alternative approach.
      Following a discussion on governance, two streams of theorising power are
      presented: mainstream and second-stream. Mainstream concepts are based on the
      notion of power-as-capacity, of one agent having the capacity to influence
      another-so the overall idea is 'power over?'. Studies on integrated care
      typically employ mainstream ideas, which yield rather limited analyses. Second
      stream concepts focus on strategies and relations of power-how it is channelled,
      negotiated and (re)produced. These notions align well with the contemporary shift
      away from the idea that power is centralised, towards more fluid ideas of power
      as dispersed and (re)negotiated throughout a range of societal structures,
      networks and actors. Accompanying this shift, the notion of governance is slowly
      being eclipsed by that of governmentality. We propose governmentality as a
      valuable perspective for analysing and understanding power in integrated care.
      Our contribution aims to address the need for more finely tuned theoretical
      frameworks that can be used to guide empirical work.

PMID- 28435427
TI  - Novel 4-thiazolidinone derivatives as agonists of benzodiazepine receptors:
      Design, synthesis and pharmacological evaluation.
AB  - A new series of 4-chloro-N-(2-(substitutedphenyl)-4-oxothiazolidin-3-yl)-2
      phenoxybenzamide derivatives were designed, synthesized and biologically
      evaluated as anticonvulsant agents. The designed compounds have the main
      essential functional groups for binding to the benzodiazepine receptors and 4
      thiazolidinone ring as an anticonvulsant pharmacophore. Some of the new
      synthesized compounds showed considerable anticonvulsant activity in electroshock
      and pentylenetetrazole-induced lethal convulsion tests. Compound 5i, 4-chloro-N
      (2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)-2-phenoxybenzamide, with the best
      activity was selected for evaluation of other benzodiazepine pharmacological
      effects. This compound induced significant sedative-hypnotic activity. However,
      it does not impair the learning and memory in the experimental condition.
      Flumazenil was able to antagonize the sedative-hypnotic and anticonvulsant
      effects of compound 5i indicating that benzodiazepine receptors are highly
      involved in the pharmacological properties of the novel compounds.

PMID- 28435428
TI  - In silico CD4+, CD8+ T-cell and B-cell immunity associated immunogenic epitope
      prediction and HLA distribution analysis of Zika virus.
AB  - Zika virus (ZIKV) is a mosquito-borne flavivirus distributed all over Africa,
      South America and Asia. The infection with the virus may cause acute febrile
      sickness that clinically resembles dengue fever, yet there is no vaccine, no
      satisfactory treatment, and no means of evaluating the risk of the disease or
      prognosis in the infected people. In the present study, the efficacy of the
      host's immune response in reducing the risk of infectious diseases was taken into
      account to carry out immuno-informatics driven epitope screening strategy of
      vaccine candidates against ZIKV. In this study, HLA distribution analysis was
      done to ensure the coverage of the vast majority of the population. Systematic
      screening of effective dominant immunogens was done with the help of Immune
      Epitope & ABCPred databases. The outcomes suggested that the predicted epitopes
      may be protective immunogens with highly conserved sequences and bear potential
      to induce both protective neutralizing antibodies, T & B cell responses. A total
      of 25 CD4+ and 16 CD8+ peptides were screened for T-cell mediated immunity. The
      predicted epitope "TGLDFSDLYYLTMNNKHWLV" was selected as a highly immunogenic
      epitope for humoral immunity. These peptides were further screened as non-toxic,
      immunogenic and non-mutated residues of envelop viral protein. The predicted
      epitope could work as suitable candidate(s) for peptide based vaccine
      development. Further, experimental validation of these epitopes is warranted to
      ensure the potential of B- and T-cells stimulation for their efficient use as
      vaccine candidates, and as diagnostic agents against ZIKV.

PMID- 28435429
TI  - Antibacterial and cytotoxic activities of naphthoquinone pigments from Onosma
      visianii Clem.
AB  - In this study, the antibacterial and cytotoxic activities of isolated compounds
      from the roots of Onosma visianii were investigated. By using different
      chromatographic techniques and appropriate spectroscopic methods, the seven
      naphthoquinones were described: deoxyshikonin ( 1 ), isobutyrylshikonin ( 2 ),
      alpha-methylbutyrylshikonin ( 3 ), acetylshikonin ( 4 ), beta
      hydroxyisovalerylshikonin ( 5 ), 5,8-O-dimethyl isobutyrylshikonin ( 6 ) and 5,8
      O-dimethyl deoxyshikonin ( 7 ). Among the tested compounds, 3 and 4 exhibited the
      highest antibacterial activities toward all tested bacterial species (MIC50 and
      MIC90 for gram positive bacteria: 6.40 MUg/mL-12.79 MUg/mL and 6.82 MUg/mL-13.60
      MUg/mL, respectively; for gram negative bacteria: 4.27 MUg/mL-8.53 MUg/mL and
      4.77 MUg/mL-9.54 MUg/mL, respectively). Also, naphthoquinones 3 and 4 exhibited
      strong cytotoxic activity against MDA-MB-231 cells (IC50 values 86.0 MUg/mL and
      80.2 MUg/mL, respectively), while compounds 1 , 3 , 4 and 5 significantly
      decreased viability of HCT116 cells (IC50 values of 97.8 MUg/mL, 15.2 MUg/mL,
      24.6 MUg/mL and 30.9 MUg/mL, respectively). Our results indicated that all tested
      naphthoquinone pigments are potential candidates for clinical uses as
      antibacterial and cytotoxic agents.

PMID- 28435430
TI  - Influence of daily oral prophylactic selenium treatment on the dibutyltin
      dichloride (DBTC)-induced pancreatitis in rats.
AB  - Dibutyltin dichloride (DBTC) is an organotin compound used as model for acute and
      chronic pancreatitis. Oxidative stress is one of the mechanisms of propagation of
      acinar cell injury in acute pancreatitis. Selenium is an essential cofactor in
      the antioxidant glutathione peroxidase pathway. Selenium levels are described to
      be subnormal in patients with acute and chronic pancreatitis. The aim of our
      studies was to determine the prophylactic effect of Na-selenite [5 mg kg-1 body
      weight (b.w.) per os (p.o.) 7 days] on the pathogenesis and course of DBTC-
      induced pancreatitis. Male inbred rats (LEW-1W Charles River) of 150 g body
      weight were used in this study. Experimental pancreatitis was induced by
      intravenous administration of 6 mg kg-1 b.w. DBTC in rats. Na-selenite was
      administered as daily oral dose of 5 mg kg-1 b.w. 7 days before induction of DBTC
      pancreatitis. Malondialdehyde (MDA) was measured for monitoring levels of
      oxidative stress. Elimination of DBTC was reflected as tin concentration in bile
      and urine. Organ changes were indicated by serum parameters as well as histology.
      A prophylactic Na-selenite application significantly diminished MDA- and
      bilirubin concentration in serum, activities of lipase and transaminases as well
      as organ injuries compared to DBTC- treated rats in the absence of Na-selenite.
      The prophylactic oral treatment with Na-selenite in the scope of DBTC-induced
      pancreatitis points to a reduced oxidative stress characterized by diminished MDA
      serum levels and a milder course of pancreatitis suggesting prophylactic
      substitution with Na-selenite to probably elicit beneficial effect on the
      clinical outcome in patients with endoscopic retrograde cholangiopancreatography
      (ERCP).

PMID- 28435431
TI  - Dioscin induces demethylation of DAPK-1 and RASSF-1alpha genes via the
      antioxidant capacity, resulting in apoptosis of bladder cancer T24 cells.
AB  - DNA methylation at CpG rich regions often occurs at tumor suppressor gene
      promoters, resulting in reduced gene expression and final carcinogenesis.
      Hypermethylation of tumor suppressor genes, including DAPK-1 and RASSF-1alpha
      genes, have been found in patients with bladder carcinoma (BC) in some western
      countries. Reactive oxygen species (ROS) was reported to play a causative role in
      gene hypermethylation. In this study, we detected the methylation status and
      expression of DAPK1 and RASSF-1alpha genes in tissue samples from Chinese BC
      patients, using methylation-specific PCR, reverse transcription PCR and western
      blotting. Further, we examined the ability of dioscin, a natural antioxidant, to
      regulate methylation status and expression of DAPK-1 and RASSF-1alpha genes in BC
      cell lines. In our results, DAPK-1 and RASSF-1alpha genes showed higher
      methylation level and lower express level in BC tissues than matched normal
      tissues. Treatment with dioscin decreased viability of BC 5637 and T24 cells, but
      not non-cancer bladder epithelial cell, SV-HUC-1. Dioscin triggered demethylation
      of DAPK1 and RASSF-1alpha genes in T24 cells and increased the gene and protein
      expression in 5637 and T24 cells. Both dioscin and substituted antioxidants (N
      acetyl cysteine and Vitamin E) decreased intracellular ROS, but the effect of
      dioscin was abolished by adding H2O2. Similar to dioscin, the substituted
      antioxidants also induced the gene demethylation and T24 cell apoptosis. Co
      treatment with dioscin and H2O2 had no such effects. Collectively, dioscin
      induces demethylation of DAPK-1 and RASSF-1alpha genes via the antioxidant
      capacity, resulting in apoptosis of bladder cancer T24 cells or inhibitory cell
      viability.

PMID- 28435433
TI  - Effect of melatonin supplemented at the light or dark period on recovery of
      sciatic nerve injury in rats.
AB  - Peripheral nerve injuries can cause disabilities, social or economic problems.
      Melatonin, the secretory product of the pineal gland has antioxidant and anti
      inflammatory actions. The aim of the present study was to investigate the effect
      of melatonin on the recovery of sciatic nerve after injury, comparing its effect
      when given in the light or the dark periods. Forty adult male Albino rats were
      allocated into four groups: control, nerve injury, nerve injury + melatonin given
      at light and nerve injury + melatonin given at dark. Nerve injury was initiated
      by clamping the sciatic nerve. Sciatic functional index (SFI) was measured
      preoperatively and postoperatively. Melatonin was given daily for six weeks.
      Recovery of the function was analyzed by functional analysis,
      electrophysiological analysis and biochemical measurement of Superoxide dismutase
      (SOD), Interleukin 1-beta (IL-1 beta), Nerve growth factor (NGF), and bcl-2.
      Melatonin improved SFI, nerve conduction velocity (NCV) and the force of
      gastrocnemius muscle contraction as compared to the untreated rats. SOD activity,
      NGF, and bcl-2 were significantly increased, while IL-1beta was significantly
      decreased after melatonin treatment as compared to the untreated injury group.
      SFI reached the control level; muscle contraction and IL-1B were significantly
      improved in the group treated with melatonin in the dark. Melatonin fastened the
      neural recovery and may be used in the treatment of nerve injury and it induced
      better nerve regeneration when the rats were treated during the dark period.

PMID- 28435432
TI  - Foundation and methodologies in computer-aided diagnosis systems for breast
      cancer detection.
AB  - Breast cancer is the most prevalent cancer that affects women all over the world.
      Early detection and treatment of breast cancer could decline the mortality rate.
      Some issues such as technical reasons, which related to imaging quality and human
      error, increase misdiagnosis of breast cancer by radiologists. Computer-aided
      detection systems (CADs) are developed to overcome these restrictions and have
      been studied in many imaging modalities for breast cancer detection in recent
      years. The CAD systems improve radiologists' performance in finding and
      discriminating between the normal and abnormal tissues. These procedures are
      performed only as a double reader but the absolute decisions are still made by
      the radiologist. In this study, the recent CAD systems for breast cancer
      detection on different modalities such as mammography, ultrasound, MRI, and
      biopsy histopathological images are introduced. The foundation of CAD systems
      generally consist of four stages: Pre-processing, Segmentation, Feature
      extraction, and Classification. The approaches which applied to design different
      stages of CAD system are summarised. Advantages and disadvantages of different
      segmentation, feature extraction and classification techniques are listed. In
      addition, the impact of imbalanced datasets in classification outcomes and
      appropriate methods to solve these issues are discussed. As well as, performance
      evaluation metrics for various stages of breast cancer detection CAD systems are
      reviewed.

PMID- 28435434
TI  - Study of the cytotoxic effects of 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone
      (MeDZQ) in mouse hepatoma cells.
AB  - A number of quinones have been shown to be efficient anticancer agents. However,
      some mechanisms of their action, in particular cell signaling are not well
      understood. The aim of this study was to partly fill this gap by characterizing
      the mode of cytotoxicity of 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone
      (MeDZQ) in malignant mouse hepatoma cells (MH-22A) with regard to the expression
      and activation of main molecules in MAPK cell signaling pathway. The study
      revealed unequal roles of MAP kinases in MeDZQ-induced cell death: the compound
      did not induce significant changes in ERK expression or its phosphorylation; JNK
      appeared to be responsible for cell survival, however, p38 kinase was shown to be
      involved in cell death. In order to assess the enzymatic activation mechanisms
      responsible for the action of MeDZQ, we have also found that the antioxidant N,N'
      diphenyl-p-phenylene diamine, the iron-chelating agent desferrioxamine, and DT
      diaphorase inhibitor, dicoumarol, partly protected the cells from MeDZQ
      cytotoxicity. It points to parallel oxidative stress and bioreductive alkylation
      modes of the cytotoxicity of MeDZQ.

PMID- 28435435
TI  - Corrigendum: Simplified Assay for Epigenetic Age Estimation in Whole Blood of
      Adults.
AB  - [This corrects the article on p. 126 in vol. 7, PMID: 27471517.].

PMID- 28435437
TI  - Lower suicide intention in patients with personality disorders admitted for
      deliberate self-poisoning than in patients with other diagnoses.
AB  - BACKGROUND: People with deliberate self-poisoning and personality disorders are
      in increased risk for suicide. Intention and psychiatric features are important
      factors in a psychiatric evaluation and for planning aftercare. METHODS: Patients
      admitted to medical departments after deliberate self-poisoning were studied (n =
      117). Patients with personality disorder according to (ICD-10, F.60-69) were
      compared to patients with affective disorders, substance use disorders, and
      unknown psychiatric diagnosis on Beck Suicide Intention Scale (SIS), Beck Suicide
      Ideation Scale (BSI), Beck Hopelessness Scale (BHS), and Beck Depression
      Inventory (BDI). RESULTS: The mean suicide intention score (SIS) was
      significantly lower among patients with personality disorders compared with
      patients with other psychiatric diagnoses 10.2 (95% CI 8.1-12.4) vs. 14.6 (95% CI
      12.7-16.4) (p = 0.040). The hopelessness scores (BHS) were significantly higher
      among patients with personality disorders 13.0 (95% CI 10.9-15.2) compared with
      patients with affective disorders 8.2 (95% CI 6.1-10.3) and substance use
      disorders 9.9 (95% CI 5.2-14.6) (p = 0.0014) and unknown psychiatric diagnoses
      10.6 (95% CI 9.1-12.2). There were no significant differences between the groups
      on suicide ideation (BSI) and depression (BDI). CONCLUSIONS: Although patients
      with personality disorders had lower suicide intention compared to patients with
      other psychiatric diagnoses, they reported significantly more hopelessness. This
      distinction is an important implication in the clinical assessment and planning
      of further treatment of DSP patients.

PMID- 28435436
TI  - Developments in our understanding of the effects of growth hormone on white
      adipose tissue from mice: implications to the clinic.
AB  - Adipose tissue (AT) is a well-established target of growth hormone (GH) and is
      altered in clinical conditions associated with excess, deficiency and absence of
      GH action. Due to the difficulty in collecting AT from clinical populations,
      genetically modified mice have been useful in better understanding how GH affects
      this tissue. Recent findings in mice would suggest that the impact of GH on AT is
      beyond alterations of lipolysis, lipogenesis or proliferation/ differentiation.
      AT depot-specific alterations in immune cells, extracellular matrix, adipokines,
      and senescence indicate an expanded role for GH in AT physiology. This mouse data
      will guide additional studies necessary to evaluate the therapeutic potential and
      safety of GH for conditions associated with altering AT, such as obesity. In this
      review, we introduce several relatively new intricacies of GH's effect on AT,
      focusing on recent studies in mice. Finally, we summarize the clinical
      implications of these findings.

PMID- 28435438
TI  - Breastfeeding woman are at higher risk of vitamin D deficiency than non
      breastfeeding women - insights from the German VitaMinFemin study.
AB  - BACKGROUND: Despite increased awareness of the adverse health effects of vitamin
      D deficiency, only a few studies have evaluated the vitamin D status (25
      hydroxyvitamin D [25(OHD)]) of breastfeeding women and up to now, no information
      exits for German breastfeeding women. Therefore, the aim of study was to
      determine the vitamin D status of breastfeeding women compared to non-pregnant
      and non-breastfeeding (NPNB) women. METHODS: This cross-sectional study
      investigated 124 breastfeeding women and 124 age and season matched NPNB women
      from the German "Vitamin and mineral status among German women" study. The study
      participants were recruited from April 2013 to March 2015 and did not take
      vitamin D supplements. Serum 25(OH)D was analyzed by chemiluminescent
      immunoassay. RESULTS: Vitamin D deficiency (<25.0 nmol/L) was prevalent in 26.6%
      of the breastfeeding women. The majority of women (49.2%) showed 25(OH)D
      concentration between 25.0 and 49.9 nmol/L. In multiple binary logistic
      regression analysis, breastfeeding women had a 4.0-fold higher odds ratio (OR)
      (95% confidence interval [CI] 1.8, 8.7) for vitamin D deficiency than NPNB women.
      For breastfeeding women, the risk of vitamin D deficiency was higher in the
      winter and spring months (OR: 2.6, 95% CI 1.1, 6.3) and increased with lower
      longitude per one unit (OR 0.7, 95% CI 0.6, 0.9). CONCLUSION: Breastfeeding women
      in Germany had a higher risk of deficient vitamin D levels than NPNB women. In
      further studies, the optimal vitamin D status for breastfeeding women should be
      investigated and also the required vitamin D doses to ensure this vitamin D
      status. TRIAL REGISTRATION: German Clinical Trial Register (identification
      number: DRKS00004789).

PMID- 28435439
TI  - Nanobiotechnology: Cell Membrane-Based Delivery Systems.
AB  - The increasingly rapid pace of research in the field of bioinspired drug delivery
      systems is revealing the promise of cell membrane-based nanovesicles for
      biomedical applications. Those cell membrane-based nanoparticles combine the
      natural functionalities of cell plasma membranes and the bioengineering
      flexibility of synthetic nanomaterials, and such versatility provides a means of
      designing exciting new drug formulations for personalized treatment in future
      nanomedicine.

PMID- 28435440
TI  - Core column prediction for protein multiple sequence alignments.
AB  - BACKGROUND: In a computed protein multiple sequence alignment, the coreness of a
      column is the fraction of its substitutions that are in so-called core columns of
      the gold-standard reference alignment of its proteins. In benchmark suites of
      protein reference alignments, the core columns of the reference alignment are
      those that can be confidently labeled as correct, usually due to all residues in
      the column being sufficiently close in the spatial superposition of the known
      three-dimensional structures of the proteins. Typically the accuracy of a protein
      multiple sequence alignment that has been computed for a benchmark is only
      measured with respect to the core columns of the reference alignment. When
      computing an alignment in practice, however, a reference alignment is not known,
      so the coreness of its columns can only be predicted. RESULTS: We develop for the
      first time a predictor of column coreness for protein multiple sequence
      alignments. This allows us to predict which columns of a computed alignment are
      core, and hence better estimate the alignment's accuracy. Our approach to
      predicting coreness is similar to nearest-neighbor classification from machine
      learning, except we transform nearest-neighbor distances into a coreness
      prediction via a regression function, and we learn an appropriate distance
      function through a new optimization formulation that solves a large-scale linear
      programming problem. We apply our coreness predictor to parameter advising, the
      task of choosing parameter values for an aligner's scoring function to obtain a
      more accurate alignment of a specific set of sequences. We show that for this
      task, our predictor strongly outperforms other column-confidence estimators from
      the literature, and affords a substantial boost in alignment accuracy.

PMID- 28435441
TI  - Comment on Haig et al. (): the conservation genetics juggling act: integrating
      genetics and ecology, science and policy.

PMID- 28435442
TI  - Response to Smith et al. 18 February 2016.

PMID- 28435443
TI  - Occurrence of plastidial triacylglycerol synthesis and the potential regulatory
      role of AGPAT in the model diatom Phaeodactylum tricornutum.
AB  - BACKGROUND: Microalgae have emerged as a potential feedstock for biofuels and
      bioactive components. However, lack of microalgal strains with promising
      triacylglycerol (TAG) content and desirable fatty acid composition have hindered
      its commercial feasibility. Attempts on lipid overproduction by metabolic
      engineering remain largely challenging in microalgae. RESULTS: In this study, a
      microalgal 1-acyl-sn-glycerol-3-phosphate acyltransferase designated AGPAT1 was
      identified in the model diatom Phaeodactylum tricornutum. AGPAT1 contained four
      conserved acyltransferase motifs I-IV. Subcellular localization prediction and
      thereafter immuno-electron microscopy revealed the localization of AGPAT1 to
      plastid membranes. AGPAT1 overexpression significantly altered the primary
      metabolism, with increased total lipid content but decreased content of total
      carbohydrates and soluble proteins. Intriguingly, AGPAT1 overexpression
      coordinated the expression of other key genes such as DGAT2 and GPAT involved in
      TAG synthesis, and consequently increased TAG content by 1.81-fold with a
      significant increase in polyunsaturated fatty acids, particularly EPA and DHA.
      Moreover, besides increased lipid droplets in the cytosol, ultrastructural
      observation showed a number of TAG-rich plastoglobuli formed in plastids.
      CONCLUSION: The results suggested that AGPAT1 overexpression could elevate TAG
      biosynthesis and, moreover, revealed the occurrence of plastidial TAG synthesis
      in the diatom. Overall, our data provide a new insight into microalgal lipid
      metabolism and candidate target for metabolic engineering.

PMID- 28435444
TI  - Role of Trichoderma reesei mitogen-activated protein kinases (MAPKs) in cellulase
      formation.
AB  - BACKGROUND: Despite being the most important cellulase producer, the cellulase
      regulating carbon source signal transduction processes in Trichoderma reesei are
      largely unknown. Elucidating these processes is the key for unveiling how
      external carbon sources regulate cellulase formation, and ultimately for the
      improvement of cellulase production and biofuel production from lignocellulose.
      RESULTS: In this work, the role of the mitogen-activated protein kinase (MAPK)
      signal transduction pathways on cellulase formation was investigated. The
      deletion of yeast FUS3-like tmk1 in T. reesei leads to improved growth and
      significantly improved cellulase formation. However, tmk1 deletion has no effect
      on the transcription of cellulase-coding genes. The involvement of the cell wall
      integrity maintenance governing yeast Slt2-like Tmk2 in cellulase formation was
      investigated by overexpressing tmk3 in T. reesei Deltatmk2 to restore cell wall
      integrity. Transcriptional analysis found little changes in cellulase-coding
      genes between T. reesei parent, Deltatmk2, and Deltatmk2::OEtmk3 strains. Cell
      wall integrity decreased in T. reesei Deltatmk2 over the parent strain and
      restored in Deltatmk2::OEtmk3. Meanwhile, cellulase formation is increased in T.
      reesei Deltatmk2 and then decreased in T. reesei Deltatmk2::OEtmk3. CONCLUSIONS:
      These investigations elucidate the role of Tmk1 and Tmk2 on cellulase formation:
      they repress cellulase formation, respectively, by repressing growth and
      maintaining cell wall integrity, while neither MAPK regulates the transcription
      of cellulase-coding genes. This work, together with the previous investigations,
      suggests that all MAPKs are involved in cellulase formation, while Tmk3 is the
      only MAPK involved in signal transduction for the regulation of cellulase
      expression on the transcriptional level.

PMID- 28435445
TI  - Cardiometabolic risk factors, metabolic syndrome and pre-diabetes in adolescents
      in the Sierra region of Ecuador.
AB  - BACKGROUND: Excess weight (overweight and obesity) is the major modifiable risk
      factor for type 2 diabetes mellitus (T2DM) and other non-communicable diseases.
      However, excess weight may not be as predictive of diabetes risk as once thought.
      While excess weight and other obesity-related non-communicable diseases are of
      growing concern in low-middle income countries in Latin America, there is limited
      research on risk factors associated with T2DM in adolescents. This study
      investigated prevalence of overweight, obesity, prediabetes, diabetes and
      metabolic syndrome in adolescents in Ecuador. METHODS: A cross-sectional study
      was conducted with 433 adolescents from two schools in a small urban center in
      southern Ecuador and two schools in a large urban center in Quito. Risk factors
      were measured, including: height, weight, BMI, waist-to-hip ratio, fasting
      glucose, lipid panel, and HbA1c. Multivariate analysis of variance (MANOVA) was
      separately applied to risk factors and demographic factors as a set of dependent
      variables with sex, location and their interaction included as predictors. An
      independent t test was run on the data at 95% confidence intervals for the mean
      difference. The values for the triglycerides, LDL and VLDL were positively
      skewed. A Mann-Whitney U test was run on these data. RESULTS: Using IOTF
      standards, 9.8% were overweight and 1.9% were obese. Only 1.6% of the sample met
      the criteria for prediabetes by fasting glucose but 12.4% of the sample met the
      criteria for prediabetes by HbA1c. None of the participants met criteria for
      diabetes. There were 2.3% of the participants that met the IDF criteria for
      metabolic syndrome. Adolescents from the larger urban center had higher rates of
      prediabetes, higher mean HbA1c, blood pressure, lipid values, and lower HDL
      levels. CONCLUSIONS: Use of HbA1c identified more adolescents with prediabetes
      than FBG. The HbA1c measure is an attractive screening tool for prediabetes in
      developing countries. Although rates of obesity in Ecuadorian adolescents are low
      there is significant evidence to suggest that prediabetes is permeating the
      smaller urban centers. Traditional screening tools may underestimate this risk.

PMID- 28435446
TI  - Cardiovascular risk assessment in patients with diabetes.
AB  - Although patients with diabetes have 2 to 4 times increased risk of
      cardiovascular morbidity and mortality than individuals without diabetes, recent
      studies indicate that a significant part of patients are in a lower
      cardiovascular risk category. Men younger than 35 years, women younger than 45
      years, patients with diabetes duration of less than 10 years without other risk
      factors have a much lower risk than patients who have traditional cardiovascular
      risk factors, and subclinical or established coronary artery disease (CAD). These
      patients are not risk equivalent as stated in previous studies. On the contrary,
      when in the presence of traditional risk factors or evidence of subclinical
      coronary disease (e.g. high coronary calcium score), the coronary risk is much
      increased and patients may be classified at a higher-risk category. Recent
      guidelines do not anymore consider diabetes as a CAD risk equivalent and
      recommend cardiovascular risk stratification for primary prevention.
      Stratification of diabetic patients improves accuracy in prediction of
      subclinical CAD, silent ischemia and future cardiovascular events. Stratification
      also discriminates higher from lower risk patients who may need intensive statin
      or aspirin prevention, while avoiding overtreatment in lower risk cases. It may
      also allow the clinician to decide whether to intensify risk reduction actions
      through specific newer drugs for glucose control such as SGLT-2 inhibitors or GLP
      1 agonists, which recently have shown additional cardiovascular protector effect.
      This review addresses the assessment of cardiovascular disease risk using
      traditional and non-traditional cardiovascular risk factors. It also reviews the
      use of risk calculators and new reclassification tools, focusing on the detection
      of subclinical atherosclerosis as well as silent ischemia in the asymptomatic
      patients with diabetes.

PMID- 28435447
TI  - A Unique Recombinant Fluoroprobe Targeting Activated Platelets Allows In Vivo
      Detection of Arterial Thrombosis and Pulmonary Embolism Using a Novel Three
      Dimensional Fluorescence Emission Computed Tomography (FLECT) Technology.
AB  - Progress in pharmaceutical development is highly-dependent on preclinical in vivo
      animal studies. Small animal imaging is invaluable for the identification of new
      disease markers and the evaluation of drug efficacy. Here, we report for the
      first time the use of a three-dimensional fluorescence bioimager called
      FLuorescence Emission Computed Tomography (FLECT) for the detection of a novel
      recombinant fluoroprobe that is safe, easily prepared on a large scale and stably
      stored prior to scan. This novel fluoroprobe (Targ-Cy7) comprises a single-chain
      antibody-fragment (scFvTarg), which binds exclusively to activated-platelets,
      conjugated to a near-infrared (NIR) dye, Cy7, for detection. Upon mouse carotid
      artery injury, the injected fluoroprobe circulates and binds within the platelet
      rich thrombus. This specific in vivo binding of the fluoroprobe to the thrombus,
      compared to its non-targeting control-fluoroprobe, is detected by the FLECT
      imager. The analyzed FLECT image quantifies the NIR signal and localizes it to
      the site of vascular injury. The detected fluorescence is further verified using
      a two-dimensional IVIS(r) Lumina scanner, where significant NIR fluorescence is
      detected in vivo at the thrombotic site, and ex vivo, at the injured carotid
      artery. Furthermore, fluorescence levels in various organs have also been
      quantified for biodistribution, with the highest fluoroprobe uptake shown to be
      in the injured artery. Subsequently, this live animal imaging technique is
      successfully employed to monitor the response of the induced thrombus to
      treatment over time. This demonstrates the potential of using longitudinal FLECT
      scanning to examine the efficacy of candidate drugs in preclinical settings.
      Besides intravascular thrombosis, we have shown that this non-invasive FLECT
      imaging can also detect in vivo pulmonary embolism. Overall, this report
      describes a novel fluorescence-based preclinical imaging modality that uses an
      easy-to-prepare and non-radioactive recombinant fluoroprobe. This represents a
      unique tool to study mechanisms of thromboembolic diseases and it will strongly
      facilitate the in vivo testing of antithrombotic drugs. Furthermore, the non
      radiation nature, low-cost, high sensitivity, and the rapid advancement of
      optical scanning technologies make this fluorescence imaging an attractive
      development for future clinical applications.

PMID- 28435448
TI  - Inhibition of platelet function using liposomal nanoparticles blocks tumor
      metastasis.
AB  - Extensive evidence has shown that platelets support tumor metastatic progression
      by inducing epithelial-mesenchymal transition of cancer cells and by shielding
      circulating tumor cells from immune-mediated elimination. Therefore, blocking
      platelet function represents a potential new avenue for therapy focused on
      eliminating metastasis. Here we show that liposomal nanoparticles bearing the
      tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) can deliver a platelet
      inhibitor, ticagrelor, into tumor tissues to specifically inhibit tumor
      associated platelets. The drug-loaded nanoparticles (CREKA-Lipo-T) efficiently
      blocked the platelet-induced acquisition of an invasive phenotype by tumor cells
      and inhibited platelet-tumor cell interaction in vitro. Intravenously
      administered CREKA-Lipo-T effectively targeted tumors within 24 h, and inhibited
      tumor metastasis without overt side effects. Thus, the CREKA-Lipo formulation
      provides a simple strategy for the efficient delivery of anti-metastatic drugs
      and shows considerable promise as a platform for novel cancer therapeutics.

PMID- 28435449
TI  - Zero-order controlled release of BMP2-derived peptide P24 from the chitosan
      scaffold by chemical grafting modification technique for promotion of
      osteogenesis in vitro and enhancement of bone repair in vivo.
AB  - Combination of tissue-engineered bone scaffolds with cell-adhesive,
      osteoconductive, or osteoinductive biomolecules is a critical strategy to improve
      their properties that significantly influence cellular behaviors, such as
      adhesion, proliferation, and differentiation, which is beneficial for critical
      sized bone defects repairing. However, the traditional surface modification
      techniques, such as physical adsorption, coating, and plasma treatment, et al,
      have great limitations for immobilization of bioactive molecules due to
      undesirable controlled delivery performance or overly complex multistep
      procedures. In this study, we functionalized the chitosan/hydroxyapatite (CS/HA)
      biomimetic composite scaffold for controlled delivery of BMP2-derived peptide
      (P24) by the chemical grafting modification technique: firstly, P24 was
      conjugated with a thiolated chitosan, chitosan-4-thiobutylamidine (CS-TBA);
      secondly, the resultant CS-P24 was then combined with HA to prepare CS-P24/HA
      scaffolds. The effect of CS-P24/HA scaffolds on bone regeneration was evaluated,
      along with the underlying biological mechanisms responsible in vitro and in vivo.
      In vitro, the controlled and sustained release of bioactive P24 could last up to
      90 days, furthermore, the release profiles of CS-5%P24/HA and CS-10%P24/HA were
      linear and could be fitted according to zero-order kinetic model (R2=0.9929;
      R2=0.9757); P24 on the scaffold significantly promoted cell adhesion,
      proliferation, osteodifferentiation, and mineralization with synergistic effects.
      Bone marrow stromal cells (BMSCs) revealed spindle-shaped surface morphology,
      indicating the CS-P24/HA scaffolds supported cell adhesion and possessed a high
      proliferation rate that varied according to the P24 concentration levels.
      Furthermore, mRNA levels for OCN, Runx2, and collagen I were significantly up
      regulated on CS-P24/HA scaffolds compared with cells grown on CS/HA scaffolds in
      vitro (p < 0.05). Similarly, the BMSCs exhibited a higher ALP expression and
      calcium deposition level on CS-P24/HA scaffolds compared with CS/HA scaffolds (p
      < 0.05). In vivo, osteoinductive studies revealed a significantly higher ectopic
      osteogenesis level of CS-10%P24/HA scaffolds in rat dorsal muscle pockets
      compared with that of CS/HA scaffolds. Finally, CS-P24/HA scaffolds showed
      superior performance in the reconstruction of rat calvarial bone defects. This
      novel CS-P24/HA scaffold is deemed a strong potential candidate for the repair of
      bone defects in human bone tissue engineering.

PMID- 28435450
TI  - Exome Sequencing of Oral Squamous Cell Carcinoma Reveals Molecular Subgroups and
      Novel Therapeutic Opportunities.
AB  - Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety
      of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC
      patients has not improved over the past decades due to its heterogeneous
      etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic
      strategies and tailored treatment options is an unmet need. To unveil the
      mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in
      Taiwan was conducted. Analyzing the contributions of the five mutational
      signatures extracted from the dataset of somatic variations identified four
      groups of tumors that were significantly associated with demographic and clinical
      features. In addition, known (TP53, FAT1, EPHA2, CDKN2A, NOTCH1, CASP8, HRAS,
      RASA1, and PIK3CA) and novel (CHUK and ELAVL1) genes that were significantly and
      frequently mutated in OSCC were discovered. Further analyses of gene alteration
      status with clinical parameters revealed that the tumors of the tongue were
      enriched with copy-number alterations in several gene clusters containing CCND1
      and MAP4K2. Through defining the catalog of targetable genomic alterations, 58%
      of the tumors were found to carry at least one aberrant event potentially
      targeted by US Food and Drug Administration (FDA)-approved agents. Strikingly, if
      targeting the p53-cell cycle pathway (TP53 and CCND1) by the drugs studied in
      phase I-III clinical trials, those possibly actionable tumors are predominantly
      located in the tongue, suggesting a better prediction of sensitivity to current
      targeted therapies. Our work revealed molecular OSCC subgroups that reflect
      etiological and prognostic correlation as well as defined the landscape of major
      altered events in the coding regions of OSCC genomes. These findings provide
      clues for the design of clinical trials for targeted therapies and stratification
      of OSCC patients with differential therapeutic efficacy.

PMID- 28435451
TI  - AHNAK2 is a Novel Prognostic Marker and Oncogenic Protein for Clear Cell Renal
      Cell Carcinoma.
AB  - Integrative database analysis was performed to identify novel candidate oncogene
      AHNAK2 overexpressed in clear cell renal cell carcinoma (ccRCC). However, the
      function of AHNAK2 in cancer cells is currently unknown. In this study, we first
      confirmed the upregulation of AHNAK2 in ccRCC tissues compared with adjacent
      normal tissues in 15 pairs of samples. Then we analyzed AHNAK2 expression in a
      large cohort of ccRCC patient samples (n = 355), and found that up-regulation of
      AHNAK2 was positively correlated with tumor progression and poor survival (p =
      0.032). Knockdown of AHNAK2 inhibited cancer cell proliferation, colony formation
      and migration in vitro and tumorigenic ability in vivo. Meanwhile, knockdown of
      AHNAK2 impaired the cell oncologic-metabolism by inhibiting lipid synthesis.
      Moreover, we observed that expression of AHNAK2 was greatly upregulated, at least
      in part, by hypoxia in cancer cells. By using chromatin immune-precipitation
      (CHIP) and promoter-luciferase reporter assays, we identified that upregulation
      of AHNAK2 induced by hypoxia was hypoxia-inducible factor-1alpha (HIF1alpha)
      dependent. Knockdown of AHNAK2 impaired hypoxia-induced epithelial-mesenchymal
      transition (EMT) and stem cell-like properties. Considered together, we reveal
      that AHNAK2 is upregulated in cancer cells and hypoxic upregulation of AHNAK2 can
      drive tumorigenesis and progression by supporting EMT and cancer cell stemness.
      Thus, AHNAK2 is a novel prognostic marker and an oncogenic protein for ccRCC.

PMID- 28435452
TI  - The YAP1/SIX2 axis is required for DDX3-mediated tumor aggressiveness and
      cetuximab resistance in KRAS-wild-type colorectal cancer.
AB  - The mechanism underlying tumor aggressiveness and cetuximab (CTX) resistance in
      KRAS-wild-type (KRAS -WT) colorectal cancer remains obscure. We here provide
      evidence that DDX3 promoted soft agar growth and invasiveness of KRAS-WT cells,
      as already confirmed in KRAS-mutated cells. Mechanistically, increased KRAS
      expression induced ROS production, which elevated HIF-1alpha and YAP1 expression.
      Increased HIF-1alpha persistently promoted DDX3 expression via a KRAS/ROS/HIF
      1alpha feedback loop. DDX3-mediated aggressiveness and CTX resistance were
      regulated by the YAP1/SIX2 axis in KRAS-WT cells and further confirmed in animal
      models. Kaplan-Meier and Cox regression analysis indicated that DDX3, KRAS, and
      YAP1 expression had prognostic value for OS and RFS in KRAS-WT and KRAS-mutated
      tumors, but SIX2 and YAP1/SIX2 were prognostic value only in KRAS-WT patients.
      The observation from patients seemed to support the mechanistic action of cell
      and animal models. We therefore suggest that combining YAP1 inhibitors with CTX
      may therefore suppress DDX3-mediated tumor aggressiveness and enhance CTX
      sensitivity in KRAS-WT colorectal cancer.

PMID- 28435453
TI  - SiRNA Delivery with PEGylated Graphene Oxide Nanosheets for Combined Photothermal
      and Genetherapy for Pancreatic Cancer.
AB  - Since the successful exfoliation of graphene from graphite in 2004, graphene and
      graphene oxide (GO) have been considered the most promising two-dimensional (2D)
      nanomaterials with distinguished physical and chemical characteristics and have
      attracted great attention in many different fields. Graphene oxide is well-known
      for its distinct physiochemical properties and shows only minimal cytotoxicity
      compared to carbon nanotubes. Until now, only limited efforts have been invested
      in utilizing GO for gene therapy in pancreatic cancer treatments. In this study,
      we utilized multi-functionalized monolayer GO as a gene delivery system to
      efficiently co-deliver HDAC1 and K-Ras siRNAs (small interfering RNAs targeting
      the HDAC1 gene and the G12C mutant K-Ras gene, respectively) to specifically
      target pancreatic cancer cells MIA PaCa-2. The systematic mechanistic elucidation
      of the dual gene silencing effects indicated the inactivation of both the HDAC1
      and the K-Ras gene, thereby causing apoptosis, proliferation inhibition and cell
      cycle arrest in treated MIA PaCa-2 cells. The synergistic combination of gene
      silencing and NIR light thermotherapy showed significant anticancer efficacy,
      inhibiting in vivo tumor volume growth by >80%. Furthermore, GO can be
      metabolized in the mouse model within a reasonable period of time without obvious
      side effects. Based on preliminary in vivo application, this study for the first
      time indicates the promising potential of functionalized GO as a vehicle for gene
      therapy delivery with low toxicity for the treatment of pancreatic
      adenocarcinoma.

PMID- 28435454
TI  - Dual Somatostatin Receptor/FDG PET/CT Imaging in Metastatic Neuroendocrine
      Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance.
AB  - Background: PET scans using FDG and somatostatin receptor imaging agents have
      both been used to study neuroendocrine tumours. Most reports have documented the
      sensitivity and specificity of each radiopharmaceutical independently, and even
      suggested the superiority of one over the other for different grades of disease.
      Aim: The aim of this work was to develop a grading scheme that describes the
      joint results of both the FDG and somatostatin receptor imaging PET scans in
      staging subjects with neuroendocrine tumours in a single combined parameter. The
      grading scheme that has been developed is referred to as the NETPET grade.
      Methods: This is a retrospective study which assessed subjects who had both FDG
      and somatostatin receptor PET imaging at our institution within 31 days of each
      other. The NETPET grade was assigned by experienced nuclear medicine physicians
      and compared with other clinical data such as WHO grade and overall survival.
      Results: In the period 2011-2015 we were able to recruit 62 subjects with
      histologically proven metastatic neuroendocrine tumour for review. The NETPET
      grade incorporating both the FDG and somatostatin receptor imaging results was
      significantly correlated with overall survival by univariate analysis (p=0.0018),
      whereas in this cohort the WHO grade at the time of diagnosis did not correlate
      with survival. Conclusions: The NETPET grade has promise as a prognostic imaging
      biomarker in neuroendocrine tumours. It permits the capturing of the complexity
      of dual radiotracer imaging in a single parameter which describes the subjects'
      disease and is readily amenable to use in patient management and further
      research.

PMID- 28435455
TI  - The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal
      Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors.
AB  - Neuroendocrine tumors (NET) are often metastatic at the time of diagnosis.
      Metastatic well-differentiated (G1/G2) NET may display a wide range of behaviors,
      ranging from indolent to aggressive, even within apparently homogeneous
      categories. Thus, selecting the optimal treatment strategy is a challenging task.
      Somatostatin receptor imaging (SRI) is the standard molecular imaging technique
      for well-differentiated NET. When performed with 68Ga-labeled somatostatin
      analogs (SRI-PET), it offers exquisite sensitivity for disease staging. SRI is
      also a prerequisite for using targeted radionuclide therapy (e.g. 177Lu
      DOTATATE). 18F-FDG imaging has traditionally been reserved for staging poorly
      differentiated G3 neuroendocrine carcinomas. However, recent data showed that FDG
      imaging has prognostic value in patients with well-differentiated NET: high
      uptake was associated with an increased risk of early progression while low
      uptake suggested an indolent tumor. In this issue of the Journal, Chan and
      colleagues propose a grading system where the results from the combined reading
      of SRI-PET and FDG-PET are reported as a single parameter, the "NETPET" score.
      While the scoring system still needs validation, it is clear that time has come
      to think about FDG and SRI in metastatic NET not as competitors but as
      complementary imaging modalities. Dual-tracer imaging can be viewed as a way to
      characterize disease phenotype in the whole-body. Moving from the prognostic
      value of dual-tracer imaging to a tool that allows for individualized management
      would require prospective trials. This editorial will argue that dual-tracer FDG
      PET and SRI-PET might influence management of patients with well-differentiated
      metastatic NET and help selecting between different therapy options.

PMID- 28435456
TI  - Physiological Effects of Ac4ManNAz and Optimization of Metabolic Labeling for
      Cell Tracking.
AB  - Metabolic labeling techniques are powerful tools for cell labeling, tracking and
      proteomic analysis. However, at present, the effects of the metabolic labeling
      agents on cell metabolism and physiology are not known. To address this question,
      in this study, we analyzed the effects of cells treated with Ac4ManNAz through
      microarray analysis and analyses of membrane channel activity, individual bio
      physiological properties, and glycolytic flux. According to the results,
      treatment with 50 MUM Ac4ManNAz led to the reduction of major cellular functions,
      including energy generation capacity, cellular infiltration ability and channel
      activity. Interestingly, 10 MUM Ac4ManNAz showed the least effect on cellular
      systems and had a sufficient labeling efficiency for cell labeling, tracking and
      proteomic analysis. Based on our results, we suggest 10 MUM as the optimum
      concentration of Ac4ManNAz for in vivo cell labeling and tracking. Additionally,
      we expect that our approach could be used for cell-based therapy for monitoring
      the efficacy of molecule delivery and the fate of recipient cells.

PMID- 28435457
TI  - Tumor Hypoxia Regulates Forkhead Box C1 to Promote Lung Cancer Progression.
AB  - Forkhead box C1 (FOXC1) is a member of the forkhead family of transcription
      factors that are characterized by a DNA-binding forkhead domain. Increasing
      evidence indicates that FOXC1 is involved in tumor progression. However, the role
      of tumor hypoxia in FOXC1 regulation and its impact on lung cancer progression
      are unclear. Here, we report that FOXC1 was upregulated in hypoxic areas of lung
      cancer tissues from rodents or humans. Hypoxic stresses significantly induced
      FOXC1 expression. Moreover, hypoxia activated FOXC1 transcription via direct
      binding of hypoxia-inducible factor-1alpha (HIF-1alpha) to the hypoxia-responsive
      element (HRE) in the FOXC1 promoter. FOXC1 gain-of-function in lung cancer cells
      promoted cell proliferation, migration, invasion, angiogenesis, and epithelial
      mesenchymal transition in vitro. However, a knockdown of FOXC1 in lung cancer
      cells inhibited these effects. Notably, knockdown of tumor hypoxia-induced FOXC1
      expression via HIF-1-mediated FOXC1 shRNAs in lung cancer xenograft models
      suppressed tumor growth and angiogenesis. Finally, systemic delivery of FOXC1
      siRNA encapsulated in lipid nanoparticles inhibited tumor growth and increased
      survival time in lung cancer-bearing mice. Taken together, these data indicate
      that FOXC1 is a novel hypoxia-induced transcription factor and plays a critical
      role in tumor microenvironment-promoted lung cancer progression. Systemic FOXC1
      blockade therapy may be an effective therapeutic strategy for lung cancer.

PMID- 28435459
TI  - Aptamer Internalization via Endocytosis Inducing S-Phase Arrest and Priming Maver
      1 Lymphoma Cells for Cytarabine Chemotherapy.
AB  - The goal of precision therapy is to efficiently treat cancer without side
      effects. Aptamers are a class of small ligands composed of single-stranded
      oligonucleotides that bind to their targets with high affinity and specificity.
      In this study, we identified an ssDNA aptamer specifically targeting Maver-1
      lymphoma cells with high binding affinity (Kd = 70+/-8 pmol/L). Interestingly,
      cellular cycle studies revealed that exposure of Maver-1 cells to synthetic
      aptamers triggered S-phase arrest of 40% of the cells (vs. 18% baseline).
      Confocal microscopy confirmed specific cell binding of aptamers and the resultant
      endocytosis into Maver-1 cells. Subsequent functional assays validated the fact
      that aptamer internalization into targeted cells is a prerequisite for Maver-1
      cell growth inhibition. Importantly, aptamer-induced S-phase arrest induced
      enhanced chemotherapeutic results involving cytarabine, which primarily kills
      lymphoma cells at S-phase. Combination treatments revealed that aptamer re
      exposure considerably primed Maver-1 cells for cytarabine chemotherapy, thus
      achieving a synergistic killing effect by reaching cell death rates as high as
      61% (vs. 13% or 14% induced by aptamer or cytarabine treatment alone). These
      findings demonstrated that aptamers do not only act as molecular ligands but can
      also function as biotherapeutic agents by inducing S-phase arrest of lymphoma
      cells. In addition, logical combination of aptamer and cytarabine treatments
      ushers the way to a unique approach in precision lymphoma chemotherapy.

PMID- 28435458
TI  - Phosphorylcholine-based stealthy nanocapsules enabling tumor microenvironment
      responsive doxorubicin release for tumor suppression.
AB  - The efficient delivery of anticancer drugs into tumor tissues to improve
      therapeutic efficacy remains an urgent demand. To satisfy this demand, a drug
      delivery system based on a stealthy nanocapsule was developed. This nanocapsule
      was fabricated by encapsulating stealthy cross-linked poly(2-methacryloyloxyethyl
      phosphorylcholine) (PMPC) and benzaldehyde groups around the protein bovine serum
      albumin (BSA) followed by conjugation of doxorubicin (Dox) through a pH
      responsive benzoic-imine bond. The in vitro results show that the Dox-conjugated
      nanocapsule (nBSA-Dox) released the drug under an acidic tumor microenvironment
      (pH ~6.5) and killed HepG2 human liver cancer cells. The half-life of Dox
      conjugated to nBSA in mice was significantly prolonged, and the area-under-curve
      of plasma Dox of the mice treated with nBSA-Dox was as much as 242 fold of free
      Dox. The in vivo results confirmed that this nanocapsule efficiently accumulated
      in tumor tissue and significantly suppressed the tumor growth.

PMID- 28435460
TI  - Size-dependent Effects of Gold Nanoparticles on Osteogenic Differentiation of
      Human Periodontal Ligament Progenitor Cells.
AB  - Gold nanoparticles (AuNPs) have been reported to promote osteogenic
      differentiation of mesenchymal stem cells and osteoblasts, but little is known
      about their effects on human periodontal ligament progenitor cells (PDLPs). In
      this study, we evaluated the effects of AuNPs with various diameters (5, 13 and
      45 nm) on the osteogenic differentiation of PDLPs and explored the underlying
      mechanisms. 5 nm AuNPs reduced the alkaline phosphatase activity, mineralized
      nodule formation and expression of osteogenic genes, while 13 and 45 nm AuNPs
      increased these osteogenic markers. Compared with 13 nm, 45 nm AuNPs showed more
      effective in promoting osteogenic differentiation. Meanwhile, autophagy was up
      regulated by 13 and 45 nm AuNPs but blocked by 5 nm AuNPs, which corresponded
      with their effects on osteogenic differentiation and indicated that autophagy
      might be involved in this process. Furthermore, the osteogenesis induced by 45 nm
      AuNPs could be reversed by autophagy inhibitors (3-methyladenine and
      chloroquine). These findings revealed that AuNPs affected the osteogenic
      differentiation of PDLPs in a size-dependent manner with autophagy as a potential
      explanation, which suggested AuNPs with defined size could be a promising
      material for periodontal bone regeneration.

PMID- 28435461
TI  - Recipient Glycemic Micro-environments Govern Therapeutic Effects of Mesenchymal
      Stem Cell Infusion on Osteopenia.
AB  - Therapeutic effects of mesenchymal stem cell (MSC) infusion have been revealed in
      various human disorders, but impacts of diseased micro-environments are only
      beginning to be noticed. Donor diabetic hyperglycemia is reported to impair
      therapeutic efficacy of stem cells. However, whether recipient diabetic condition
      also affects MSC-mediated therapy is unknown. We and others have previously shown
      that MSC infusion could cure osteopenia, particularly in ovariectomized (OVX)
      mice. Here, we discovered impaired MSC therapeutic effects on osteopenia in
      recipient type 1 diabetes (T1D). Through intensive glycemic control by daily
      insulin treatments, therapeutic effects of MSCs on osteopenia were maintained.
      Interestingly, by only transiently restoration of recipient euglycemia using
      single insulin injection, MSC infusion could also rescue T1D-induced osteopenia.
      Conversely, under recipient hyperglycemia induced by glucose injection in OVX
      mice, MSC-mediated therapeutic effects on osteopenia were diminished.
      Mechanistically, recipient hyperglycemic micro-environments reduce anti
      inflammatory capacity of MSCs in osteoporotic therapy through suppressing MSC
      interaction with T cells via the Adenosine monophosphate-activated protein kinase
      (AMPK) pathway. We further revealed in diabetic micro-environments, double
      infusion of MSCs ameliorated osteopenia by anti-inflammation, attributed to the
      first transplanted MSCs which normalized the recipient glucose homeostasis.
      Collectively, our findings uncover a previously unrecognized role of recipient
      glycemic conditions controlling MSC-mediated therapy, and unravel that
      fulfillment of potent therapeutic effects of MSCs requires tight control of
      recipient micro-environments.

PMID- 28435462
TI  - A Programmed Nanoparticle with Self-Adapting for Accurate Cancer Cell Eradication
      and Therapeutic Self-Reporting.
AB  - To achieve the best therapeutic efficacy and good prognosis, the drugs
      necessitate tailored profiles of excellent spatiotemporal control and therapeutic
      monitoring. Here we introduce a programmed theranostic nanoparticle with self
      adapting properties for tumor-specific systemic treatment, including stealthy
      surface to prolong circulation time in blood, surface charge-reversion for tumor
      targeting, receptor-mediated internalization to increase intracellular
      accumulation, "proton sponge effect" for controllable drug release and escape
      from endo/lysosome. Encouragingly, in the process of drug-induced apoptosis, the
      therapeutic efficacy can be reported by fluorescence imaging in vivo, in situ and
      in real time. Therefore, this work provides a new paradigm for design of
      programmed theranositc nanomedicine and offers promising prospects for precise
      tumor treatment.

PMID- 28435463
TI  - Design and Development of Fluorescent Vemurafenib Analogs for In Vivo Imaging.
AB  - Herein we describe fluorescent derivatives of vemurafenib to probe therapeutic
      BRAF inhibition in live cells and in vivo. The compounds were evaluated and
      compared by determining target binding, inhibition of mutant BRAF melanoma cell
      lines and live cell imaging. We show that vemurafenib-BODIPY is a superior
      imaging drug to visualize the targets of vemurafenib in live cells and in vivo in
      non-resistant and resistant melanoma tumors.

PMID- 28435464
TI  - Clinical efficacy of omalizumab in chronic spontaneous urticaria is associated
      with a reduction of FcepsilonRI-positive cells in the skin.
AB  - Background. Treatment with omalizumab, a humanized recombinant monoclonal anti
      IgE antibody, results in clinical efficacy in patients with Chronic Spontaneous
      Urticaria (CSU). The mechanism of action of omalizumab in CSU has not been
      elucidated in detail. Objectives. To determine the effects of omalizumab on
      levels of high affinity IgE receptor-positive (FcepsilonRI+) and IgE-positive
      (IgE+) dermal cells and blood basophils. Treatment efficacy and safety were also
      assessed. Study design. In a double-blind study, CSU patients aged 18-75 years
      were randomized to receive 300 mg omalizumab (n=20) or placebo (n=10)
      subcutaneously every 4 weeks for 12 weeks. Changes in disease activity were
      assessed by use of the weekly Urticaria Activity Score (UAS7). Circulating IgE
      levels, basophil numbers and levels of expression of FcepsilonRI+ and IgE+ cells
      in the skin and in blood basophils were determined. Results. Patients receiving
      omalizumab showed a significantly greater decrease in UAS7 compared with patients
      receiving placebo. At Week 12 the mean difference in UAS7 between treatment
      groups was -14.82 (p=0.0027), consistent with previous studies. Total IgE levels
      in serum were increased after omalizumab treatment and remained elevated up to
      Week 12. Free IgE levels decreased after omalizumab treatment. Mean levels of
      FcepsilonRI+ skin cells in patients treated with omalizumab 300 mg were decreased
      at Week 12 compared with baseline in the dermis of both non-lesional and lesional
      skin, reaching levels comparable with those seen in healthy volunteers (HVs).
      There were no statistically significant changes in mean FcERI+ cell levels in the
      placebo group. Similar results were seen for changes in IgE+ cells, although the
      changes were not statistically significant. The level of peripheral blood
      basophils increased immediately after treatment start and returned to Baseline
      values after the follow-up period. The levels of FcepsilonRI and IgE expression
      on peripheral blood basophils were rapidly reduced by omalizumab treatment up to
      Week 12. Conclusions. Treatment with omalizumab resulted in rapid clinical
      benefits in patients with CSU. Treatment with omalizumab was associated with
      reduction in FcERI+ and IgE+ basophils and intradermal cells.

PMID- 28435466
TI  - Design of Tumor Acidity-Responsive Sheddable Nanoparticles for
      Fluorescence/Magnetic Resonance Imaging-Guided Photodynamic Therapy.
AB  - Imaging-guided cancer therapy, which integrates diagnostic and therapeutic
      functionalities into a single system, holds great promise to enhance the accuracy
      of diagnosis and improve the efficacy of therapy. Specifically, for photodynamic
      therapy (PDT), it is highly desirable to precisely focus laser light onto the
      tumor areas to generate reactive oxygen species (ROS) that are cytotoxic tumor
      cells and avoid light-associated side effects. Herein, a distinct three-layer
      nanostructured particle with tumor acidity-responsiveness (S-NP) that
      encapsulates the photosensitizer chlorin e6 (Ce6) and chelates Gd3+ is
      successfully developed for fluorescence/magnetic resonance (MR) dual-model
      imaging-guided precision PDT. We show clear evidence that the outer PEG layer
      significantly prolongs circulation time, and the inner poly(epsilon-caprolactone)
      (PCL) core can physically encapsulate Ce6. More interestingly, the middle layer
      of the S-NP, acting as a molecular fence to keep Ce6 in the circulation system,
      was dismantled by the slightly acidic tumor microenvironment. Afterwards, the PEG
      shell is deshielded from the S-NP at the tumor tissue, resulting in improved cell
      uptake, enlarged MR signal intensity, rapid release of Ce6 within tumor cells,
      and elevated PDT efficacy. Our results suggest that tumor-acidity-responsive
      nanoparticles with fine design could serve as a theranostic platform with great
      potential in imaging-guided PDT treatment of cancer.

PMID- 28435465
TI  - Hypertension, cerebrovascular impairment, and cognitive decline in aged
      AbetaPP/PS1 mice.
AB  - Cardiovascular risk factors, especially hypertension, are also major risk factors
      for Alzheimer's disease (AD). To elucidate the underlying vascular origin of
      neurodegenerative processes in AD, we investigated the relation between systolic
      blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain
      structure and function in a 16-18 months old double transgenic AbetaPPswe/PS1dE9
      (AbetaPP/PS1) mouse model for AD. These aging AbetaPP/PS1 mice showed an
      increased SBP linked to a declined regional CBF. Furthermore, using advanced MRI
      techniques, decline of functional and structural connectivity was revealed in the
      AD-like mice coupled to impaired cognition, increased locomotor activity, and
      anxiety-related behavior. Post mortem analyses demonstrated also increased
      neuroinflammation, and both decreased synaptogenesis and neurogenesis in the
      AbetaPP/PS1 mice. Additionally, deviant levels of fatty acids and sterols were
      present in the brain tissue of the AbetaPP/PS1 mice indicating maladapted brain
      fatty acid metabolism. Our findings suggest a link between increased SBP,
      decreased cerebral hemodynamics and connectivity in an AD mouse model during
      aging, leading to behavioral and cognitive impairments. As these results mirror
      the complex clinical symptomatology in the prodromal phase of AD, we suggest that
      this AD-like murine model could be used to investigate prevention and treatment
      strategies for early AD patients. Moreover, this study helps to develop more
      efficient therapies and diagnostics for this very early stage of AD.

PMID- 28435468
TI  - Does H2 Alter Mitochondrial Bioenergetics via GHS-R1alpha Activation?
AB  - More than 400 original articles have been published from 2007 onwards evaluating
      therapeutic potential of molecular hydrogen (H2), the youngest member of medical
      gases family with selective anti-oxidative properties. However, recent studies
      suggest that H2 may tackle other mitochondrial processes besides oxidative
      stress, including metabolic pathways that drive cellular energy.

PMID- 28435467
TI  - Ultrasound Elastography: Review of Techniques and Clinical Applications.
AB  - Elastography-based imaging techniques have received substantial attention in
      recent years for non-invasive assessment of tissue mechanical properties. These
      techniques take advantage of changed soft tissue elasticity in various
      pathologies to yield qualitative and quantitative information that can be used
      for diagnostic purposes. Measurements are acquired in specialized imaging modes
      that can detect tissue stiffness in response to an applied mechanical force
      (compression or shear wave). Ultrasound-based methods are of particular interest
      due to its many inherent advantages, such as wide availability including at the
      bedside and relatively low cost. Several ultrasound elastography techniques using
      different excitation methods have been developed. In general, these can be
      classified into strain imaging methods that use internal or external compression
      stimuli, and shear wave imaging that use ultrasound-generated traveling shear
      wave stimuli. While ultrasound elastography has shown promising results for non
      invasive assessment of liver fibrosis, new applications in breast, thyroid,
      prostate, kidney and lymph node imaging are emerging. Here, we review the basic
      principles, foundation physics, and limitations of ultrasound elastography and
      summarize its current clinical use and ongoing developments in various clinical
      applications.

PMID- 28435469
TI  - Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic
      Myelogenous Leukemia cell growth.
AB  - Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved
      prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and
      long-term adverse effects is still being encountered. There is, therefore, urgent
      need to develop alternative strategies to overcome drug resistance. According to
      the molecules expressed on their surface, exosomes can target specific cells.
      Exosomes can also be loaded with a variety of molecules, thereby acting as a
      vehicle for the delivery of therapeutic agents. In this study, we engineered
      HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of
      Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML blasts
      compared to normal hematopoietic cells and thus is able to act as a receptor
      target in a cancer drug delivery system. Here we show that IL3L exosomes, loaded
      with Imatinib or with BCR-ABL siRNA, are able to target CML cells and inhibit in
      vitro and in vivo cancer cell growth.

PMID- 28435470
TI  - Downregulation of SIRT7 by 5-fluorouracil induces radiosensitivity in human
      colorectal cancer.
AB  - 5-Fluorouracil (5-FU) combined with radiotherapy is a common treatment strategy
      to treat human cancers, but the underlying mechanisms of this combination
      treatment remain unclear. Here, we report that NAD+-dependent deacetylase sirtuin
      7 (SIRT7) protein levels were decreased due to 5-FU exposure rendering colorectal
      cancer cells sensitive to radiation. We found that SIRT7 downregulation was
      mediated via a Tat-binding Protein 1 (TBP1) proteasome-dependent pathway.
      Specifically, TBP1 was dephosphorylated at tyrosine 381 upon 5-FU treatment,
      which enhanced its direct interaction with SIRT7 and targeted it for degradation.
      Depletion of SIRT7 in cultured colorectal cancer cells induced radiosensitivity
      triggering cell death. Interestingly, decreased levels of SIRT7 mediated by 5-FU
      correlated well with improved therapeutic effect in patients with rectal cancer
      and with inhibited tumor growth in immune-compromised mice post-irradiation.
      Taken together, these data suggest that 5-FU induces radiosensitivity via SIRT7
      degradation to favor a cell death pathway in targeted cancer cells. Thus,
      downregulation of SIRT7 could be a promising pharmacologic strategy to increase
      the effectiveness of chemoradiation therapy in cancer patients.

PMID- 28435472
TI  - Simultaneous targeting of CD44 and EpCAM with a bispecific aptamer effectively
      inhibits intraperitoneal ovarian cancer growth.
AB  - CD44 and EpCAM play crucial roles in intraperitoneal ovarian cancer development.
      In this study, we developed an RNA-based bispecific CD44-EpCAM aptamer that is
      capable of blocking CD44 and EpCAM simultaneously by fusing single CD44 and EpCAM
      aptamers with a double stranded RNA adaptor. With the aid of a panel of ovarian
      cancer cell lines, we found that bispecific CD44-EpCAM aptamer was much more
      effective than either single CD44 or EpCAM aptamer in the ability to inhibit cell
      growth and to induce apoptosis. When these aptamers were tested in
      intraperitoneal ovarian cancer xenograft model, bispecific CD44-EpCAM aptamer
      suppressed intraperitoneal tumor outgrowth much more significantly than single
      CD44 and EpCAM aptamer either alone or in combination. The enhanced efficacy of
      bispecific CD44-EpCAM aptamer is most likely to be attributed to its increased
      circulation time over the single aptamers. Moreover, we showed that bispecific
      CD44-EpCAM aptamer exhibited no toxicity to the host and was unable to trigger
      innate immunogenicity. Our study suggests that bispecific CD44-EpCAM aptamer may
      represent a promising therapeutic agent against advanced ovarian cancer.

PMID- 28435471
TI  - Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics
      Delivery to Breast Cancer.
AB  - Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic
      potential, yet their clinical application has been hampered by the lack of
      appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as
      a targeted delivery system for small RNAs. EVs are cell-derived small vesicles
      that participate in cell-to-cell communication for protein and RNA delivery. We
      used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to
      breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to
      nucleolin, which is highly expressed on the surface membrane of breast cancer
      cells. This delivery vesicle targeted let-7 miRNA delivery to MDA-MB-231 cells in
      vitro as confirmed with fluorescent microscopic imaging and flow cytometry. Also,
      intravenously delivered AS1411-EVs loaded with miRNA let-7 labeled with the
      fluorescent marker, Cy5, selectively targeted tumor tissues in tumor-bearing mice
      and inhibited tumor growth. Importantly, the modified EVs were well tolerated and
      showed no evidence of nonspecific side effects or immune response. Thus, the RNAi
      nanoplatform is versatile and can deliver siRNA or miRNA to breast cancer cells
      both in vitro and in vivo. Our results suggest that the AS1411-EVs have a great
      potential as drug delivery vehicles to treat cancers.

PMID- 28435474
TI  - The Vision of "Industrie 4.0" in the Making-a Case of Future Told, Tamed, and
      Traded.
AB  - Since industrial trade fair Hannover Messe 2011, the term "Industrie 4.0" has
      ignited a vision of a new Industrial Revolution and has been inspiring a lively,
      ongoing debate among the German public about the future of work, and hence
      society, ever since. The discourse around this vision of the future eventually
      spread to other countries, with public awareness reaching a temporary peak in
      2016 when the World Economic Forum's meeting in Davos was held with the motto
      "Mastering the Fourth Industrial Revolution." How is it possible for a vision
      originally established by three German engineers to unfold and bear fruit at a
      global level in such a short period of time? This article begins with a summary
      of the key ideas that are discussed under the label Industrie 4.0. The main
      purpose, based on an in-depth discourse analysis, is to debunk the myth about the
      origin of this powerful vision and to trace the narrative back to the global
      economic crisis in 2009 and thus to the real actors, central discourse patterns,
      and hidden intentions of this vision of a new Industrial Revolution. In
      conclusion, the discourse analysis reveals that this is not a case of
      visioneering but one of a future told, tamed, and traded.

PMID- 28435473
TI  - Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of
      nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1.
AB  - Cancer stem cells (CSCs) are a small subset of malignant cells, possessing
      stemness, with strong tumorigenic capability, conferring resistance to therapy
      and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study
      suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like
      side population (SP) cells in NPC. In the present study, we further found that
      COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial
      dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying
      both sorted SP cells from NPC cell lines and gene expression analyses in NPC
      tissues. Using both overexpression and knockdown of COX-2, we demonstrated that
      the localization of COX-2 at mitochondria promotes the stemness of NPC by
      recruiting the mitochondrial translocation of p53, increasing the activity of
      Drp1 and inducing mitochondrial fisson. Inhibition of the expression or the
      activity of Drp1 by siRNA or Mdivi-1 downregulates the stemness of NPC. The
      present study also found that inhibition of mitochondrial COX-2 with resveratrol
      (RSV), a natural phytochemical, increased the sensitivity of NPC to 5
      fluorouracil (5-FU), a classical chemotherapy drug for NPC. The underlying
      mechanism is that RSV suppresses mitochondrial COX-2, thereby reducing NPC
      stemness by inhibiting Drp1 activity as demonstrated in both the in vitro and the
      in vivo studies. Taken together, the results of this study suggest that
      mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC.
      Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for
      the effective clinical treatment of therapy-resistant NPC.

PMID- 28435475
TI  - Linear and Bilateral Multinucleated Cell Angiohistiocytoma (MCAH).
AB  - BACKGROUND: Multinucleated Cell Angiohistiocytoma (MCAH) is a rare disease, first
      described by Smith and Wilson Jones in 1985. Since then, less than 100 cases have
      been reported in the literature. Clinically it is characterized by papules or
      plaques arising from a specific anatomical area such as lower extremities, dorsum
      of the hands and face. Some generalized cases have been reported. MAIN
      OBSERVATIONS: We report a case of 77-year-old woman who presented with multiple
      itching. reddish to violaceous, flat to domed-shaped plaques on the lower legs
      with symmetrical and bilateral distribution along the saphena veins. On
      dermoscopy examination only a red-violaceous homogeneous area was visible.
      Histology showed remarkable proliferation of dilated small vessels in the upper
      and mid dermis and bizarre-shaped multinucleate giant cells with scalloped
      cytoplasm that were intermingled with numerous mononucleated spindle cells. Many
      mast cells containing the characteristic granules were also detected, often
      adjacent to the multinucleate cells. Based on the clinico-pathologic findings the
      diagnosis of MCAH was established. CONCLUSIONS: To our knowledge, this is the
      first documented case of MCAH with a bilateral and linear pattern disposed on the
      lower limbs, following the saphena veins. In this patient chronic trauma induced
      by ambulation might have contributed to development of the lesions.

PMID- 28435476
TI  - Successful treatment of bullous lichen planus with acitretin monotherapy. Review
      of treatment options for bullous lichen planus and case report.
AB  - BACKGROUND: Bullous lichen planus (BLP) is a rare variant of lichen planus,
      characterized by the development of vesicular and bullous lesions, of skin,
      nails, hair and/or mucosa. MAIN OBSERVATIONS: We present a case of 63-year-old
      woman with BLP, unresponsive to previous therapies with topical corticosteroids,
      topical calcipotriol, antihistamines and oral cyclosporine (4 mg/kg/day for 4
      months). She was already receiving treatment for arterial hypertension,
      hyperlipidemia, atrial fibrillation and uncontrolled diabetes mellitus. Acitretin
      was administered for 5 months with complete remission of BLP lesions and no major
      side effects. CONCLUSIONS: This is probably the first reported case of BLP
      treated with acitretin monotherapy. In this case acitretin was an efficacious and
      well-tolerated therapeutic option for BLP.

PMID- 28435477
TI  - Acrodermatitis enteropathica in a pair of twins.
AB  - BACKGROUND: Acrodermatitis enteropathica (AE) is a rare autosomal recessive
      metabolic disorder. First described by Brandt in 1936 and was named by Danbolt. A
      mutation in the SLC39A4 gene on chromosome 8 q24.3 is responsible for this
      disorder, which encodes zinc transporter Zip4. The diagnosis is made by the
      clinical presentation and histopathology and laboratory tests. In this case, we
      reported a twin presented with a typical rash and low zinc level. To our
      knowledge, very few cases reported as a twin with typical acrodermatitis
      enteropathica presentation. MAIN OBSERVATIONS: Four months old twins both
      females, first children of a non-consanguineous marriage. The twins were born at
      term, caesarian section, with no complications. Presented with erythema, scaling,
      crusting and oozing over perioral, perianal areas, hands and feet of 2-3 week
      duration. The lesions started around the same time for both children with a
      history of intermittent diarrhea, and hair loss. There were no nail changes or
      neurological deficit or myopathy. There was a history of recent weaning from
      breast milk and now both children on formula feeds, ragi, fruits. There was no
      other significant history of other medical problems in the patients or in their
      family. On examination, erythema, scaling, crusting and oozing over perioral,
      perianal areas, hands and feet was seen. Minimal diffuse alopecia was noted.
      Nails were normal. No other abnormalities were observed. Clinical diagnosis of
      acrodermatitis enteropathica was considered and confirmed by low zinc levels
      (repeated plasma zinc levels were below 0.6 mcg/ml). The twins were managed with
      zinc supplementation 1 mg/kg/day. A significant improvement was seen within two
      weeks. CONCLUSIONS: Early diagnosis of acrodermatitis enteropathica is essential
      for preventing complications. We report a rare case of typical clinical
      presentation of the disease developing simultaneously in twins.

PMID- 28435478
TI  - Disseminated extrafacial rosacea with papulonecrotic lesions.
AB  - BACKGROUND: Rosacea is a common skin disease and predominantly affects on the
      face of middle-aged women. It exceptionally occurs on the extrafacial areas such
      as ear, neck, axilla, and upper extremities, and has been reported as
      disseminated rosacea. MAIN OBSERVATION: A 40-year-old Japanese female presented
      with one-month history of erythematous skin eruption with burning sensation on
      the face, neck, and upper limbs. Physical examination showed rosacea-like
      eruption on the face as well as multiple papules disseminated on the neck,
      forearms, and hands. These extrafacial lesions demonstrated papulonecrotic
      appearance. Bilateral conjunctiva showed marked hyperemic which was consistent
      with ocular rosacea. Corneal opacity was also seen. Histology of the umbilicated
      papule on the neck revealed necrobiotic granulomas around the hair follicle with
      transepidermal elimination. Another tiny solid papule on the forearm suggesting
      early lesion also demonstrated necrobiosis with palisading granuloma but no
      transepidermal elimination. Systemic administration of minocycline and topical
      tacrolimus therapy promptly improved the skin lesions. Topical application of
      fluorometholone in temporary addition with levofloxacin improved ocular
      involvement 12 weeks after her 1st visit. The clinical course of the skin lesion
      and ocular symptoms mostly correlated. Then, the skin lesion and ocular symptoms
      often relapsed. Rosacea uncommonly associates with the extrafacial involvement as
      disseminated rosacea. The present case is characterized by the disseminated
      papulonecrotic lesions of the extrafacial areas histologically showing
      transepidermal elimination of necrobiotic granulomas. CONCLUSIONS: Dermatologists
      should recognize that papulonecrotic lesions of the neck and upper extremities
      might be extrafacial rosacea when the patient has rosacea on the face.

PMID- 28435479
TI  - A novel program for ABSN students to generate interest in geriatrics and
      geriatric nursing research.
AB  - The current shortage of nurse researchers in geriatrics adversely affects the
      capacity of nurses to conduct research to advance the evidence-based care of
      older adults. In an effort to generate interest in geriatrics and geriatric
      nursing research, the Duke University School of Nursing designed a summer
      internship for four students enrolled in the accelerated baccalaureate nursing
      (ABSN) program. This paper describes the experience of these ABSN students and
      the staff and faculty who worked with them. The program design, staff and faculty
      experiences, benefits and challenges, as well as recommendations for future
      programs are discussed. The purpose of this article is to highlight the benefits
      and challenges of offering research experiences to nursing students in an ABSN
      program to stimulate interest in geriatrics and geriatric nursing research.

PMID- 28435480
TI  - The Time Is Now to Use Clinical Outcomes as Quality Indicators for Effective
      Leadership in Trauma.

PMID- 28435481
TI  - A Patient-Centered Emergency Department Management Strategy for Sickle-Cell
      Disease Super-Utilizers.
AB  - INTRODUCTION: A subpopulation of sickle-cell disease patients, termed super
      utilizers, presents frequently to emergency departments (EDs) for vaso-occlusive
      events and may consume disproportionate resources without broader health benefit.
      To address the healthcare needs of this vulnerable patient population, we piloted
      a multidisciplinary intervention seeking to create and use individualized patient
      care plans that alter utilization through coordinated care. Our goals were to
      assess feasibility primarily, and to assess resource use secondarily. METHODS: We
      evaluated the effects of a single-site interventional study targeted at a
      population of adult sickle-cell disease super-utilizers using a pre- and post
      implementation design. The pre-intervention period was 06/01/13 to 12/31/13
      (seven months) and the post-intervention period was 01/01/14 to 02/28/15 (14
      months). Our approach included patient-specific best practice advisories (BPA);
      an ED management protocol; and formation of a "medical home" for these patients.
      RESULTS: For 10 subjects targeted initially we developed and implemented
      coordinated care plans; after deployment, we observed a tendency toward reduction
      in ED and inpatient utilization across all measured indices. Between the
      annualized pre- and post-implementation periods we found the following: ED visits
      decreased by 16.5 visits/pt-yr (95% confidence interval [CI] [-1.32-34.2]); ED
      length of state (LOS) decreased by 115.3 hours/pt-yr (95% CI [-82.9-313.5]); in
      patient admissions decreased by 4.20 admissions/pt-yr (95% CI [-1.73-10.1]); in
      patient LOS decreased by 35.8 hours/pt-yr (95% CI [-74.9-146.7]); and visits
      where the patient left before treatment were reduced by an annualized total of
      13.7 visits. We observed no patient mortality in our 10 subjects, and no patient
      required admission to the intensive care unit 72 hours following discharge.
      CONCLUSION: This effort suggests that a targeted approach is both feasible and
      potentially effective, laying a foundation for broader study.

PMID- 28435482
TI  - State Emergency Department Opioid Guidelines: Current Status.
AB  - INTRODUCTION: The purpose of this study was to evaluate and categorize current
      state-sponsored opioid guidelines for the practice of emergency medicine (EM).
      METHODS: We conducted a comprehensive search of EM-specific opioid prescribing
      guidelines and/or policies in each state to determine current state involvement
      in EM opioid prescribing, as well as to evaluate some of the specifics of each
      guideline or policy. The search was conducted using an online query and a follow
      up email request to each state chapter of ACEP. RESULTS: We found that 17 states
      had emergency department-specific guidelines. We further organized the guidelines
      into four categories: limiting prescriptions for opioids with 67 total
      recommendations; preventing/diverting abuse with 56 total recommendations;
      addiction-related guidelines with 29 total recommendations; and a community
      resources section with 24 total recommendations. Our results showed that current
      state guidelines focus on providers limiting opioid pain prescriptions and
      vetting patients for possible abuse/diversion. CONCLUSION: This study highlights
      the 17 states that have addressed opioid prescribing guidelines and categorizes
      their efforts to date. It is hoped that this study will provide the basis for
      similar efforts in other states.

PMID- 28435483
TI  - Cross-Sectional Study of Risky Substance Use by Injured Emergency Department
      Patients.
AB  - INTRODUCTION: Survey data regarding the prevalence of risky substance use in the
      emergency department (ED) is not consistent. The objective of this study was to
      identify the prevalence of risky substance use among injured ED patients based on
      the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST v3.0). A
      secondary objective was to report on the feasibility of administering the ASSIST
      to this population, based on the time to conduct screening. METHODS: This cross
      sectional study used screening data from a randomized controlled trial. Injured
      ED patients completed the ASSIST on a tablet computer, and an ASSIST score was
      computed that indicated the need for a brief or intensive treatment intervention
      (risky use) for alcohol and other substances. For a subsample, data on time to
      complete each step of screening was recorded. RESULTS: Between July 2010 and
      March 2013, 5,695 patients completed the ASSIST. Most (92%) reported lifetime use
      of at least one substance and 51% reported current risky use of at least one
      substance. Mean time to complete the ASSIST was 5.4 minutes and screening was
      considered feasible even when paused for clinical care to proceed. CONCLUSION:
      Estimates of risky substance use based on the ASSIST in our large sample of
      injured ED patients were higher than previously reported in other studies of ED
      patients, possibly due to the current focus on an injured population. In
      addition, it was feasible to administer the ASSIST to patients in the course of
      their clinical care.

PMID- 28435484
TI  - Outcomes by Mode of Transport of ST Elevation MI Patients in the United Arab
      Emirates.
AB  - INTRODUCTION: The purpose of this multicenter study was to assess differences in
      demographics, medical history, treatment times, and follow-up status among
      patients with ST-elevation myocardial infarction (STEMI), who were transported to
      the hospital by emergency medical services (EMS) or by private vehicle, or were
      transferred from other medical facilities. METHODS: This multicenter study
      involved the collection of both retrospective and prospective data from 455
      patients admitted to four hospitals in Abu Dhabi. We collected electronic medical
      records from EMS and hospitals, and conducted interviews with patients in person
      or via telephone. Chi-square tests and Kruskal-Wallis tests were used to examine
      differences in variables by mode of transportation. RESULTS: Results indicated
      significant differences in modes of transportation when considering symptom-onset
      to-balloon time (p < 0.001), door-to-balloon time (p < 0.001), and health status
      at six-month and one-year follow-up (p < 0.001). Median times (interquartile
      range) for patients transported by EMS, private vehicle, or transferred from an
      outside facility were as follows: symptom-onset-to-balloon time in hours, 3.1
      (1.8-4.3), 3.2 (2.1-5.3), and 4.5 (3.0-7.5), respectively; door-to-balloon time
      in minutes, 70 (48-78), 81 (64-105), and 62 (46-77), respectively. In all cases,
      EMS transportation was associated with a shorter time to treatment than other
      modes of transportation. However, the EMS group experienced greater rates of in
      hospital events, including cardiac arrest and mortality, than the private
      transport group. CONCLUSION: Our results contribute data supporting EMS
      transportation for patients with acute coronary syndrome. Although a lack of
      follow-up data made it difficult to draw conclusions about long-term outcomes,
      our findings clearly indicate that EMS transportation can speed time to
      treatment, including time to balloon inflation, potentially reducing readmission
      and adverse events. We conclude that future efforts should focus on encouraging
      the use of EMS and improving transfer practices. Such efforts could improve
      outcomes for patients presenting with STEMI.

PMID- 28435485
TI  - Impact of Health Policy Changes on Emergency Medicine in Maryland Stratified by
      Socioeconomic Status.
AB  - INTRODUCTION: On January 1, 2014, the financing and delivery of healthcare in the
      state of Maryland (MD) profoundly changed. The insurance provisions of the
      Patient Protection and Affordable Care Act (ACA) began implementation and a major
      revision of MD's Medicare waiver ushered in a Global Budget Revenue (GBR)
      structure for hospital reimbursement. Our objective was to analyze the impact of
      these policy changes on emergency department (ED) utilization, hospitalization
      practices, insurance profiles, and professional revenue. We stratified our
      analysis by the socioeconomic status (SES) of the ED patient population. METHODS:
      We collected monthly mean data including patient volume, hospitalization
      percentages, payer mix, and professional revenue from January 2013 through
      December 2015 from a convenience sample of 11 EDs in Maryland. Using regression
      models, we compared each of the variables 18 months after the policy changes and
      a six-month washout period to the year prior to ACA/GBR implementation. We
      included the median income of each ED's patient population as an explanatory
      variable and stratified our results by SES. RESULTS: Our 11 EDs saw an annualized
      volume of 399,310 patient visits during the study period. This ranged from a mean
      of 41 daily visits in the lowest volume rural ED to 171 in the highest volume
      suburban ED. After ACA/GBR, ED volumes were unchanged (95% confidence interval
      [CI] [-1.58-1.24], p=.817). Hospitalization percentages decreased significantly
      by 1.9% from 17.2% to 15.3% (95% CI [-2.47%-1.38%], p<.001). The percentage of
      uninsured patients decreased from 20.4% to 11.9%. This 8.5% change was
      significant (95% CI [-9.20%-7.80%], p<.001). The professional revenue per
      relative value unit increased significantly by $3.97 (95% CI [3.20-4.74],
      p<.001). When stratified by the median patient income of each ED, changes in each
      outcome were significantly more pronounced in EDs of lower SES. CONCLUSION:
      Health policy changes at the federal and state levels have resulted in
      significant changes to emergency medicine practice and finances in MD. Admission
      and observation percentages have been reduced, fewer patients are uninsured, and
      professional revenue has increased. All changes are significantly more pronounced
      in EDs with patients of lower SES.

PMID- 28435486
TI  - Prevalence of Homelessness in the Emergency Department Setting.
AB  - INTRODUCTION: According to the National Alliance to End Homelessness, the
      national rate of homelessness has been cited as 17.7 homeless people/10,000
      people in the general population, and 24.8 homeless veterans/10,000 veterans in
      the general population. However, it is unknown what the prevalence of
      homelessness is in the emergency department (ED) setting. We set out to determine
      the prevalence of homelessness or at risk for homelessness in the ED setting.
      METHODS: Using a five-question screening tool derived from the U.S. Department of
      Housing and Urban Development, Health and Human Services and the Veterans
      Administration definition for homelessness, we surveyed all patients meeting
      inclusion/exclusion criteria on scheduled shifts in one of three EDs in
      Northeastern Pennsylvania. To participate, subjects had to be a registered
      patient in the ED, be 18 years or older, speak English, have the capacity to
      answer survey questions, not be critically ill, be willing to participate, and
      not have taken the survey before. We selected two survey periods to represent
      seasonal variations. RESULTS: We included 4,395 subjects in the analysis. The
      mean age of those who screened positive for homelessness or at risk for
      homelessness was 43.1 (SD 16.6). Overall, 136 (3.1%) participants screened
      positive for at risk for homelessness and 309 (7.0%) screened positive for
      homelessness. A total of 103 subjects (9.8%) screened positive for homelessness
      or at risk for homelessness on weekends and 312 (10.3%) on weekdays (p=0.64). The
      proportion of those screening positive for homelessness or at risk for
      homelessness varied by site: 145 (7.5%) at the trauma center, 151(9.1%) at the
      suburban site, and 149 (18.7%) at the center city site, p<0.001.There was no
      statistical significance to the difference between the trauma center and the
      suburban site (p=.088), but there was statistical significance between both the
      suburban and the trauma center when compared to the center city site (both
      p<0.0001). The proportion of those screening positive for homelessness in the
      summer months (156, 7.5%) was similar to those in the winter months (153, 6.6%),
      p=0.23. CONCLUSION: In our study, the overall prevalence of homelessness or at
      risk for homelessness was 10.1 percent. This prevalence did not seem to vary
      between weekdays and weekends. Additionally, summer months had a prevalence that
      was as concerning as winter months. The prevalence does, however, seem to vary by
      institutional characteristics even in the same geographic region. Understanding
      the patterns of prevalence of homelessness is a step toward considering possible
      interventions to assist this vulnerable population.

PMID- 28435487
TI  - Randomized Trial of Adding Parenteral Acetaminophen to Prochlorperazine and
      Diphenhydramine to Treat Headache in the Emergency Department.
AB  - INTRODUCTION: Headaches represent over three million emergency department (ED)
      visits per year, comprising 2.4% of all ED visits. There are many proposed
      methods and clinical guidelines of treating acute headache presentations.
      However, data on intravenous acetaminophen usage in these settings are lacking.
      In this study, we sought to determine the efficacy of intravenous (IV)
      acetaminophen as an adjunct to a standard therapy for the treatment of patients
      who present to the ED with a chief complaint of "headache." METHODS: We conducted
      a single site, randomized, double-blind, placebo-controlled trial investigating
      the clinical efficacy of IV acetaminophen as an adjunct to a standard therapy
      with prochlorperazine and diphenhydramine for the treatment of patients who
      present to the ED with a chief complaint of "headache" or variants thereof. (See
      below for variants). The primary outcome measure of the efficacy of parenteral
      acetaminophen as an adjunct treatment for headache in addition to a standard
      therapy was a threshold two-point reduction in visual analog scale (VAS) pain
      scores on a 1-10 level at 90 minutes. Secondary outcomes measures included
      assessment of decreased requirement of "rescue" pain medicines, defined as any
      analgesic medications outside of diphenhydramine, prochlorperazine and
      acetaminophen, with particular interest to potential opioid-sparing effects with
      parenteral acetaminophen. Additional secondary outcome measure included time to
      disposition from arrival in the ED. RESULTS: For the acetaminophen group the
      initial mean pain score was 8.67, for the placebo group 8.61. At 90 minutes pain
      score was 2.23 for the acetaminophen group and 3.99 for placebo (p<0.01, 95%
      confidence interval (CI) [0.8%-16%]. Of 45 patients in each group, we observed at
      least a threshold two-point decrease in pain score 36/45 (80%) with acetaminophen
      vs. 25/45 (55%) with placebo (p <0.01) 95% CI [5%-41%], number needed to treat
      (NNT) = 4). Secondary outcome measure did not demonstrate a difference in length
      of stay (161 minutes for acetaminophen arm and 159 minutes for placebo). However,
      17/45 (38%) of patients who received IV acetaminophen required rescue analgesia,
      opposed to 24/45 (53%) of patients in the placebo group (p=0.13) 95% CI [-5%
      34%]. CONCLUSION: IV acetaminophen when used with prochlorperazine and
      diphenhydramine to treat acute headaches in the ED resulted in statistically
      significant pain reduction compared with prochlorperazine and diphenhydramine
      alone as measured by both threshold of lowering VAS pain score by at least two
      points (NNT = 4) and overall decline in VAS pain score. Further study is required
      to validate these results.

PMID- 28435488
TI  - Clinician-Performed Bedside Ultrasound in Improving Diagnostic Accuracy in
      Patients Presenting to the ED with Acute Dyspnea.
AB  - INTRODUCTION: Diagnosing acute dyspnea is a critical action performed by
      emergency physicians (EP). It has been shown that ultrasound (US) can be
      incorporated into the work-up of the dyspneic patient; but there is little data
      demonstrating its effect on decision-making. We sought to examine the impact of a
      bedside, clinician-performed cardiopulmonary US protocol on the clinical
      impression of EPs evaluating dyspneic patients, and to measure the change in
      physician confidence with the leading diagnosis before and after US. METHODS: We
      conducted a prospective observational study of EPs treating adult patients with
      undifferentiated dyspnea in an urban academic center, excluding those with a
      known cause of dyspnea after evaluation. Outcomes: 1) percentage of post-US
      diagnosis matching final diagnosis; 2) percentage of time US changed providers'
      leading diagnosis; and 3) change in physicians' confidence with the leading
      diagnosis before and after US. An US protocol was developed and standardized
      prior to the study. Providers (senior residents, fellows, attendings) were
      trained on US (didactics, hands on) prior to enrollment, and were supervised by
      an US faculty member. After patient evaluation, providers listed likely
      diagnoses, documenting their confidence level with their leading diagnosis (scale
      of 1-10). After US, providers revised their lists and their reported confidence
      level with their leading diagnosis. Proportions are reported as percentages with
      95% confidence interval (CI) and continuous variables as medians with quartiles.
      We used the Wilcoxon signed-rank test and Cohen's kappa statistics to analyze
      data. RESULTS: A total of 115 patients were enrolled (median age: 61 [51, 73],
      59% female). The most common diagnosis before US was congestive heart failure
      (CHF) (41%, 95%CI, 32-50%), followed by chronic obstructive pulmonary disease
      (COPD) and asthma. CHF remained the most common diagnosis after US (46%, 95%CI,
      38-55); COPD became less common (pre-US, 22%, 95%CI, 15-30%; post-US, 17%, 95%CI,
      11-24%). Post-US clinical diagnosis matched the final diagnosis 63% of the time
      (95%CI, 53-70%), compared to 69% pre-US (95%CI, 60-76%). Fifty percent of
      providers changed their leading diagnosis after US (95%CI, 41-59%). Overall
      confidence of providers' leading diagnosis increased after US (7 [6, 8]) vs. 9
      [8, 9], p: 0.001). CONCLUSION: Bedside US did not improve the diagnostic accuracy
      in physicians treating patients presenting with acute undifferentiated dyspnea.
      US, however, did improve providers' confidence with their leading diagnosis.

PMID- 28435489
TI  - Gender Differences in CDC Guideline Compliance for STIs in Emergency Departments.
AB  - INTRODUCTION: Sexually transmitted infections (STIs) are a common reason for
      emergency department (ED) visits. The objective of this study was to determine if
      there were gender differences in adherence to Centers for Disease Control and
      Prevention (CDC) STI diagnosis and treatment guidelines, as documented by
      emergency providers. METHODS: We performed a retrospective chart review to
      identify patients treated for urethritis, cervicitis, and pelvic inflammatory
      disease (PID) in the EDs of three hospitals in a Pennsylvania network during a
      calendar year. Cases were reviewed to assess for compliance with CDC guidelines.
      We used descriptive statistics to assess the distributions of study variables by
      patient sex. In the analysis we used Student's t-tests, chi-square tests, and
      logistic regression. Statistical significance was set at p <= 0.05. RESULTS: We
      identified 286 patient records. Of these, we excluded 39 for the following
      reasons: incorrect disease coding; the patient was admitted and treated as an
      inpatient for his/her disease; or the patient left the ED after refusing care. Of
      the 247 participants, 159 (64.4%) were female. Females were significantly younger
      (26.6 years, SD=8.0) than males (31.2, SD=11.5%), (95% confidence interval [CI]
      [2.0- 7.0], p=0.0003). All of the males (n=88) in the cohort presented with
      urethritis; 25.8% of females presented with cervicitis, and 74.2% with PID.
      Physician compliance for the five CDC criteria ranged from 68.8% for patient
      history to 93.5% for patient diagnostic testing, including urine pregnancy and
      gonorrhea/chlamydia cultures. We observed significant differences by patient sex.
      Fifty-four percent of the charts had symptoms recorded for female patients that
      were consistent with CDC characteristics for diagnostic criteria compared to over
      95% for males, OR=16.9; 95% CI [5.9-48.4], p<0.001. Similar results were observed
      for patient discharge instructions, with physicians completely documenting
      delivery of discharge instructions to 51.6% of females compared to 97.7% of
      complete documentation in males, OR=42.3; 95% CI [10.0-178.6] p<0.001). We
      observed no significant sex differences in physician documentation for physical
      exam or for therapeutic antibiotic treatment. CONCLUSION: This retrospective
      study found patient gender differences in how emergency providers complied with
      documenting with regard to the 2010 CDC guidelines for the diagnosis and
      treatment of urethritis, cervicitis, and PID. Specifically medical records of men
      were more likely to have complete documentation of symptoms recorded (95% CI 5.9
      48.4) and to have discharge instruction documentation (95% CI 10.0-178.6) than
      records of women.

PMID- 28435490
TI  - Correlation of Physical Exam Findings with Fever in Patients with Skin and Soft
      Tissue Infections.
AB  - INTRODUCTION: The objectives of this study were to determine the prevalence of
      fever in adult ED patients with skin and soft tissue infections (SSTI) and to
      determine which, if any, physical exam, radiograph and laboratory test findings
      were associated with fever. METHODS: We conducted a prospective, observational
      study at an urban county trauma center of adults who presented to the ED for
      evaluation of suspected SSTI. ED providers measured area of erythema and
      induration using a tape measure, and completed data sheets indicating comorbid
      conditions and the presence or absence of physical exam findings. Fever was
      defined as any recorded temperature >= 38 degrees C during the first six hours of
      ED evaluation. RESULTS: Of the 734 patients enrolled, 96 (13.1%) had fever.
      Physical and laboratory exam findings associated with the presence of a fever in
      multivariable logistic regression were the area of erythema, particularly the
      largest quartile of area of erythema, 144 - 5,000 cm2, (odd ratio [OR] = 2.9; 95%
      confidence interval [CI] [1.6 - 5.2]) and leukocytosis (OR = 4.4, 95% CI [2.7 -
      7.0]). Bullae, necrosis, streaks, adenopathy, and bone involvement on imaging
      were not associated with fever. CONCLUSION: Fever is uncommon in patients
      presenting to the ED for evaluation of suspected SSTI. Area of erythema and
      leukocytosis were associated with fever and should be considered in future
      decision rules for the evaluation and treatment of SSTI.

PMID- 28435491
TI  - Agreement Between Serum Assays Performed in ED Point-of-Care and Hospital Central
      Laboratories.
AB  - INTRODUCTION: Point-of-care (POC) testing allows for more time-sensitive
      diagnosis and treatment in the emergency department (ED) than sending blood
      samples to the hospital central laboratory (CL). However, many ED patients have
      blood sent to both, either out of clinical custom, or because clinicians do not
      trust the POC values. The objective of this study was to examine the level of
      agreement between POC and CL values in a large cohort of ED patients. METHODS: In
      an urban, Level I ED that sees approximately 120,000 patients/year, all patients
      seen between March 1, 2013, and October 1, 2014, who had blood sent to POC and CL
      labs had levels of agreement measured between serum sodium, potassium, blood urea
      nitrogen (BUN), creatinine, and hematocrit. We extracted data from the hospital's
      clinical information system, and analyzed agreement with the use of Bland-Altman
      plots, defining both 95% confidence intervals (CIs) and more conservative CIs
      based on clinical judgment. RESULTS: Out of 163,661 patients seen during the
      study period, 14,567 had blood samples sent both for POC and CL analysis. Using
      clinical criteria, the levels of agreement for sodium were 98.6% (within 5mg/dL),
      for potassium 90.7% (0.5 mmol/L), for BUN 89.0% (within 5 mg/dL), for creatinine
      94.5% (within 0.3 mg/dL), for hematocrit 96.5% (within 5 g/dL). CONCLUSION:
      Agreement between POC and CL values is excellent. Restricting the analysis to
      clinically important levels of agreement continues to show a high level of
      agreement. The data suggest that sending a serum sample to the hospital CL for
      duplicate assays is unnecessary. This may result in substantial savings and
      shorter ED lengths of stay.

PMID- 28435492
TI  - Applying Systems Engineering Reduces Radiology Transport Cycle Times in the
      Emergency Department.
AB  - INTRODUCTION: Emergency department (ED) crowding is widespread, and can result in
      care delays, medical errors, increased costs, and decreased patient satisfaction.
      Simultaneously, while capacity constraints on EDs are worsening, contributing
      factors such as patient volume and inpatient bed capacity are often outside the
      influence of ED administrators. Therefore, systems engineering approaches that
      improve throughput and reduce waste may hold the most readily available gains.
      Decreasing radiology turnaround times improves ED patient throughput and
      decreases patient waiting time. We sought to investigate the impact of systems
      engineering science targeting ED radiology transport delays and determine the
      most effective techniques. METHODS: This prospective, before-and-after analysis
      of radiology process flow improvements in an academic hospital ED was exempt from
      institutional review board review as a quality improvement initiative. We
      hypothesized that reorganization of radiology transport would improve radiology
      cycle time and reduce waste. The intervention included systems engineering
      science-based reorganization of ED radiology transport processes, largely using
      Lean methodologies, and adding no resources. The primary outcome was average
      transport time between study order and complete time. All patients presenting
      between 8/2013-3/2016 and requiring plain film imaging were included. We analyzed
      electronic medical record data using Microsoft Excel and SAS version 9.4, and we
      used a two-sample t-test to compare data from the pre- and post-intervention
      periods. RESULTS: Following the intervention, average transport time decreased
      significantly and sustainably. Average radiology transport time was 28.7 +/- 4.2
      minutes during the three months pre-intervention. It was reduced by 15% in the
      first three months (4.4 minutes [95% confidence interval [CI] 1.5-7.3]; to 24.3
      +/- 3.3 min, P=0.021), 19% in the following six months (5.4 minutes, 95% CI [2.7
      8.2]; to 23.3 +/- 3.5 min, P=0.003), and 26% one year following the intervention
      (7.4 minutes, 95% CI [4.8-9.9]; to 21.3 +/- 3.1 min, P=0.0001). This result was
      achieved without any additional resources, and demonstrated a continual trend
      towards improvement. This innovation demonstrates the value of systems
      engineering science to increase efficiency in ED radiology processes. CONCLUSION:
      In this study, reorganization of the ED radiology transport process using systems
      engineering science significantly increased process efficiency without additional
      resource use.

PMID- 28435493
TI  - Prehospital Care for the Adult and Pediatric Seizure Patient: Current Evidence
      based Recommendations.
AB  - INTRODUCTION: We sought to develop evidence-based recommendations for the
      prehospital evaluation and treatment of adult and pediatric patients with a
      seizure and to compare these recommendations against the current protocol used by
      the 33 emergency medical services (EMS) agencies in California. METHODS: We
      performed a review of the evidence in the prehospital treatment of patients with
      a seizure, and then compared the seizure protocols of each of the 33 EMS agencies
      for consistency with these recommendations. We analyzed the type and route of
      medication administered, number of additional rescue doses permitted, and
      requirements for glucose testing prior to medication. The treatment for eclampsia
      and seizures in pediatric patients were analyzed separately. RESULTS: Protocols
      across EMS Agencies in California varied widely. We identified multiple drugs,
      dosages, routes of administration, re-dosing instructions, and requirement for
      blood glucose testing prior to medication delivery. Blood glucose testing prior
      to benzodiazepine administration is required by 61% (20/33) of agencies for adult
      patients and 76% (25/33) for pediatric patients. All agencies have protocols for
      giving intramuscular benzodiazepines and 76% (25/33) have protocols for
      intranasal benzodiazepines. Intramuscular midazolam dosages ranged from 2 to 10
      mg per single adult dose, 2 to 8 mg per single pediatric dose, and 0.1 to 0.2
      mg/kg as a weight-based dose. Intranasal midazolam dosages ranged from 2 to 10 mg
      per single adult or pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose.
      Intravenous/intrasosseous midazolam dosages ranged from 1 to 6 mg per single
      adult dose, 1 to 5 mg per single pediatric dose, and 0.05 to 0.1 mg/kg as a
      weight-based dose. Eclampsia is specifically addressed by 85% (28/33) of
      agencies. Forty-two percent (14/33) have a protocol for administering magnesium
      sulfate, with intravenous dosages ranging from 2 to 6 mg, and 58% (19/33) allow
      benzodiazepines to be administered. CONCLUSION: Protocols for a patient with a
      seizure, including eclampsia and febrile seizures, vary widely across California.
      These recommendations for the prehospital diagnosis and treatment of seizures may
      be useful for EMS medical directors tasked with creating and revising these
      protocols.

PMID- 28435494
TI  - The Efficacy of LUCAS in Prehospital Cardiac Arrest Scenarios: A Crossover
      Mannequin Study.
AB  - INTRODUCTION: High-quality cardiopulmonary resuscitation (CPR) is critical for
      successful cardiac arrest outcomes. Mechanical devices may improve CPR quality.
      We simulated a prehospital cardiac arrest, including patient transport, and
      compared the performance of the LUCASTM device, a mechanical chest compression
      decompression system, to manual CPR. We hypothesized that because of the movement
      involved in transporting the patient, LUCAS would provide chest compressions more
      consistent with high-quality CPR guidelines. METHODS: We performed a crossover
      controlled study in which a recording mannequin was placed on the second floor of
      a building. An emergency medical services (EMS) crew responded, defibrillated,
      and provided either manual or LUCAS CPR. The team transported the mannequin
      through hallways and down stairs to an ambulance and drove to the hospital with
      CPR in progress. Critical events were manually timed while the mannequin recorded
      data on compressions. RESULTS: Twenty-three EMS providers participated. Median
      time to defibrillation was not different for LUCAS compared to manual CPR
      (p=0.97). LUCAS had a lower median number of compressions per minute (112/min vs.
      125/min; IQR = 102-128 and 102-126 respectively; p<0.002), which was more
      consistent with current American Heart Association CPR guidelines, and percent
      adequate compression rate (71% vs. 40%; IQR = 21-93 and 12-88 respectively;
      p<0.002). In addition, LUCAS had a higher percent adequate depth (52% vs. 36%;
      IQR = 25-64 and 29-39 respectively; p<0.007) and lower percent total hands-off
      time (15% vs. 20%; IQR = 10-22 and 15-27 respectively; p<0.005). LUCAS performed
      no differently than manual CPR in median compression release depth, percent fully
      released compressions, median time hands off, or percent correct hand position.
      CONCLUSION: In our simulation, LUCAS had a higher rate of adequate compressions
      and decreased total hands-off time as compared to manual CPR. Chest compression
      quality may be better when using a mechanical device during patient movement in
      prehospital cardiac arrest patient.

PMID- 28435495
TI  - Areas of Potential Impact of the Patient Protection and Affordable Care Act on
      EMS: A Synthesis of the Literature.
AB  - INTRODUCTION: This comprehensive review synthesizes the existing literature on
      the Patient Protection and Affordable Care Act (ACA) as it relates to emergency
      medical services (EMS) in order to provide guidance for navigating current and
      future healthcare changes. METHODS: We conducted a comprehensive review to
      identify all existing literature related to the ACA and EMS and all sections
      within the federal law pertaining to EMS. RESULTS: Many changes enacted by the
      ACA directly affect emergency care with potential indirect effects on EMS
      systems. New Medicaid enrollees and changes to existing coverage plans may alter
      EMS transport volumes. Reimbursement changes such as adjustments to the ambulance
      inflation factor (AIF) alter the yearly increases in EMS reimbursement by
      incorporating the multifactor productivity value into yearly reimbursement
      adjustments. New initiatives, funded by the Center for Medicare & Medicaid
      Innovation are exploring novel and cost-effective prehospital care delivery
      opportunities while EMS agencies individually explore partnerships with
      healthcare systems. CONCLUSION: EMS systems should be aware of the direct and
      indirect impact of ACA on prehospital care due to the potential for changes in
      financial reimbursement, acuity and volume changes, and ongoing new care delivery
      initiatives.

PMID- 28435496
TI  - "Choosing Wisely" Imaging Recommendations: Initial Implementation in New England
      Emergency Departments.
AB  - INTRODUCTION: In June 2016, the American College of Emergency Physicians (ACEP)
      Emergency Quality Network began its Reduce Avoidable Imaging Initiative, designed
      to "reduce testing and imaging with low risk patients through the implementation
      of Choosing Wisely recommendations." However, it is unknown whether New England
      emergency departments (ED) have already implemented evidence-based interventions
      to improve adherence to ACEP Choosing Wisely recommendations related to imaging
      after their initial release in 2013. Our objective was to determine this, as well
      as whether provider-specific audit and feedback for imaging had been implemented
      in these EDs. METHODS: This survey study was exempt from institutional review
      board review. In 2015, we mailed surveys to 195 hospital-affiliated EDs in all
      six New England states to determine whether they had implemented Choosing Wisely
      focused interventions in 2014. Initial mailings included cover letters denoting
      the endorsement of each state's ACEP chapter, and we followed up twice with
      repeat mailings to non-responders. Data analysis included descriptive statistics
      and a comparison of state differences using Fisher's exact test. RESULTS: A total
      of 169/195 (87%) of New England EDs responded, with all individual state response
      rates >80%. Overall, 101 (60%) of responding EDs had implemented an intervention
      for at least one Choosing Wisely imaging scenario; 57% reported implementing a
      specific guideline/policy/clinical pathway and 28% reported implementing a
      computerized decision support system. The most common interventions were for
      chest computed tomography (CT) in patients at low risk of pulmonary embolism (47%
      of EDs) and head CT in patients with minor trauma (45% of EDs). In addition, 40%
      of EDs had implemented provider-specific audit and feedback, without significant
      interstate variation (range: 29-55%). CONCLUSION: One year after release of the
      ACEP Choosing Wisely recommendations, most New England EDs had a
      guideline/policy/clinical pathway related to at least one of the recommendations.
      However, only a minority of them were using provider-specific audit and feedback
      or computerized decision support. Few EDs have embraced the opportunity to
      implement the multiple evidence-based interventions likely to advance the
      national goals of improving patient-centered and resource-efficient care.

PMID- 28435497
TI  - Improved Accuracy and Quality of Information During Emergency Department Care
      Transitions.
AB  - INTRODUCTION: Suboptimal communication during emergency department (ED) care
      transitions has been shown to contribute to medical errors, sometimes resulting
      in patient injury and litigation. The study objective was to determine whether a
      standardized checkout process would decrease the number of relevant missed
      clinical items (MCI). METHODS: In this prospective pre- and post-intervention
      study conducted in an urban academic ED, we collected data on omitted or
      inaccurately conveyed medical information before and after the initiation of a
      standardized checkout process. The intervention included group checkout in an
      optimal location, review of electronic medical records, case discussion and
      assigned roles. MCI were considered relevant if they resulted in a delay or
      alteration in disposition or treatment plan. The primary outcome was the change
      in the number of MCI. Secondary outcomes were duration of checkout and physician
      satisfaction with the intervention. RESULTS: Pre-intervention, there were 94
      relevant MCI during 164 care transitions. Post-intervention, there were 36 MCI in
      157 transitions. The mean MCI per transition decreased by 58% from 0.57 (95%
      confidence interval [CI] [0.41, 0.73]) to 0.23 (95% CI [0.11-0.35]). Instituting
      the intervention did not lengthen checkout duration, which was 15 minutes (95% CI
      [13.81-16.19]) pre-intervention and 14 minutes (95% CI [12.99-15.01]) post
      intervention. The majority of participants (73.4%) felt that the process
      decreased MCI, and 89.5% reported that the new process had a positive or neutral
      effect on their satisfaction with care transitions. CONCLUSION: The adoption of a
      standardized care transition process markedly decreased clinically relevant
      communication errors without lengthening checkout duration.

PMID- 28435498
TI  - Security, Violent Events, and Anticipated Surge Capabilities of Emergency
      Departments in Washington State.
AB  - INTRODUCTION: Over the past 15 years, violent threats and acts against hospital
      patients, staff, and providers have increased and escalated. The leading area for
      violence is the emergency department (ED) given its 24/7 operations, role in
      patient care, admissions gateway, and center for influxes during acute surge
      events. This investigation had three objectives: to assess the current security
      of Washington State EDs; to estimate the prevalence of and response to threats
      and violence in Washington State EDs; and to appraise the Washington State ED
      security capability to respond to acute influxes of patients, bystanders, and
      media during acute surge events. METHODS: A voluntary, blinded, 28-question Web
      based survey developed by emergency physicians was electronically delivered to
      all 87 Washington State ED directors in January 2013. We evaluated responses by
      descriptive statistical analyses. RESULTS: Analyses occurred after 90% (78/87) of
      ED directors responded. Annual censuses of the EDs ranged from < 20,000 to
      100,000 patients and represented the entire spectrum of practice environments,
      including critical access hospitals and a regional quaternary referral medical
      center. Thirty-four of 75 (45%) reported the current level of security was
      inadequate, based on the general consensus of their ED staff. Nearly two-thirds
      (63%) of EDs had 24-hour security personnel coverage, while 28% reported no
      assigned security personnel. Security personnel training was provided by 45% of
      hospitals or healthcare systems. Sixty-nine of 78 (88%) respondents witnessed or
      heard about violent threats or acts occurring in their ED. Of these, 93% were
      directed towards nursing staff, 90% towards physicians, 74% towards security
      personnel, and 51% towards administrative personnel. Nearly half (48%) noted
      incidents directed towards another patient, and 50% towards a patient's family or
      friend. These events were variably reported to the hospital administration. After
      an acute surge event, 35% believed the initial additional security response would
      not be adequate, with 26% reporting no additional security would be available
      within 15 minutes. CONCLUSION: Our study reveals the variability of ED security
      staffing and a heterogeneity of capabilities throughout Washington State. These
      deficiencies and vulnerabilities highlight the need for other EDs and regional
      emergency preparedness planners to conduct their own readiness assessments.

PMID- 28435499
TI  - The Fast and the Furious: Low-Risk Chest Pain and the Rapid Rule-Out Protocol.
AB  - Accelerated diagnostic pathways (ADP) have been designed to identify low-risk
      chest pain patients in the emergency department. This review article discusses
      the Asia-Pacific Evaluation of Chest Pain Trial (ASPECT) score, the Accelerated
      Diagnostic Protocol for Chest Pain Trial (ADAPT) score, the Emergency Department
      Assessment of Chest Pain Score (EDACS), the HEARTScore and the HEART pathway.
      These ADPs have been validated in various studies and aid the emergency provider
      with identifying the low-risk chest pain patient who is appropriate for discharge
      home, while at the same time highlighting those patients who would benefit from
      further in-patient work up. These approaches should be paired with patient input
      and shared decision-making strategies.

PMID- 28435500
TI  - Skin to Intramuscular Compartment Thigh Measurement by Ultrasound in Pediatric
      Population.
AB  - INTRODUCTION: Pediatric obesity threatens the efficacy of medications given
      intramuscularly. In anaphylactic patients, epinephrine auto-injector needle
      lengths are potentially too short to reach the muscle compartment in patients
      with elevated body habitus. The objective of the study was to determine needle
      length requirements for intramuscular injections in pediatric patients. METHODS:
      We used ultrasound to measure the distance from skin to muscle compartment of the
      thigh in 200 pediatric patients of various weight and body mass index who
      presented to the emergency department. RESULTS: Patients with higher body mass
      index had an increased distance to muscle and bone. If current recommendations
      were followed, 5% of patients within the EpiPen adult weight category and 11% of
      patients within the Centers for Disease Control and Prevention weight category
      would have potentially used a needle inadequate in length for intramuscular
      injections. CONCLUSION: With the increase in childhood obesity, needle lengths
      may be too short to effectively deliver medications to the intramuscular
      compartment. Needle length should be evaluated to accommodate pediatric patients
      with increased skin to muscle distance.

PMID- 28435501
TI  - Impact of Clinical Decision Support on Radiography for Acute Ankle Injuries: A
      Randomized Trial.
AB  - INTRODUCTION: While only 15-20% of patients with foot and ankle injuries
      presenting to urgent care centers have clinically significant fractures, most
      undergo radiography. We examined the impact of electronic point-of-care clinical
      decision support (CDS) on adherence to the Ottawa Ankle Rules (OAR), as well as
      use and yield of foot and ankle radiographs in patients with acute ankle injury.
      METHODS: We obtained institutional review board approval for this randomized
      controlled study performed April 18, 2012-December 15, 2013. All ordering
      providers credentialed at an urgent care affiliated with a quaternary care
      academic hospital were randomized to either receive or not receive CDS, based on
      the OAR and integrated into the physician order-entry system, with feedback at
      the time of imaging order. If the patient met OAR low-risk criteria, providers
      were advised against imaging and could either cancel the order or ignore the
      alert. We identified patients with foot and ankle complaints via ICD-9 billing
      codes and electronic health records and radiology reports reviewed for those who
      were eligible. Chi-square was used to compare adherence to the OAR (primary
      outcome), radiography utilization rate and radiography yield of foot and ankle
      imaging (secondary outcomes) between the intervention and control groups.
      RESULTS: Of 14,642 patients seen at urgent care during the study period, 613
      (4.2%, representing 632 visits) presented with acute ankle injury and were
      eligible for application of the OAR; 374 (59.2%) of these were seen by control
      group providers. In the intervention group, CDS adherence was higher for both
      ankle (239/258=92.6% vs. 231/374=61.8%, p=0.02) and foot radiography
      (209/258=81.0% vs. 238/374=63.6%; p<0.01). However, ankle radiography use was
      higher in the intervention group (166/258=64.3% vs. 183/374=48.9%; p<0.01), while
      foot radiography use (141/258=54.6% vs. 202/374=54.0%; p=0.95) was not.
      Radiography yield was also higher in the intervention group (26/307=8.5% vs.
      18/385=4.7%; p=0.04). CONCLUSION: Clinical decision support, previously
      demonstrated to improve guideline adherence for high-cost imaging, can also
      improve guideline adherence for radiography - as demonstrated by increased OAR
      adherence and increased imaging yield.

PMID- 28435502
TI  - Inferior Vena Cava Measurement with Ultrasound: What Is the Best View and Best
      Mode?
AB  - INTRODUCTION: Intravascular volume status is an important clinical consideration
      in the management of the critically ill. Point-of-care ultrasonography (POCUS)
      has gained popularity as a non-invasive means of intravascular volume assessment
      via examination of the inferior vena cava (IVC). However, there are limited data
      comparing different acquisition techniques for IVC measurement by POCUS. The goal
      of this evaluation was to determine the reliability of three IVC acquisition
      techniques for volume assessment: sub-xiphoid transabdominal long axis (LA),
      transabdominal short axis (SA), and right lateral transabdominal coronal long
      axis (CLA) (aka "rescue view"). METHODS: Volunteers were evaluated by three
      experienced emergency physician sonographers (EP). Gray scale (B-mode) and motion
      mode (M-mode) diameters were measured and IVC collapsibility index (IVCCI)
      calculated for three anatomic views (LA, SA, CLA). For each IVC measurement, we
      calculated descriptive statistics, intra-class correlation coefficients (ICC),
      and two-way univariate analyses of variance. RESULTS: EPs evaluated 39
      volunteers, yielding 351 total US measurements. Measurements of the three views
      had similar means (LA 1.9 +/- 0.4cm; SA 1.9 +/- 0.4cm; CLA 2.0 +/- 0.5cm). For B
      Mode, LA had the highest ICC (0.86, 95% CI [0.76-0.92]) while CLA had the poorest
      ICC (0.74, 95% CI [0.56-0.85]). ICCs for all M-mode IVCCI were low. Significant
      interaction effects between anatomical view and EP were observed for B-mode and M
      mode measurements. Post-hoc analyses revealed difficulty in consistent view
      acquisition between EPs. CONCLUSION: Inter-rater reliability of the IVC by EPs
      was highest for B-mode LA and poorest for all M-Mode IVC collapsibility indices
      (IVCCI). These results suggest that B-mode LA holds the most promise to deliver
      reliable measures of IVC diameter. Future studies may focus on validation in a
      clinical setting as well as comparison to a reference standard.

PMID- 28435503
TI  - Ultrasound-Guided Radial Artery Compression to Assess Blood Pressure.
AB  - INTRODUCTION: We proposed using compression sonography to observe the coaptation
      and collapse of the radial artery as a surrogate for automated cuff blood
      pressures (BP). We hypothesize that the pressure required to achieve coaptation
      and complete collapse of the artery would correlate to the diastolic and systolic
      BP, respectively. This pilot study was to assess the feasibility of ultrasound
      guided radial artery compression (URAC) for BP measurement and compare patient
      comfort levels during automated cuff with URAC measurements. METHODS: This was a
      prospective cohort pilot study with a convenience sampling of 25 adult patients
      at a single urban emergency department. URAC pressure was measured, followed by
      cuff manometry on the same arm. A 100mL normal saline bag was connected to the
      Stryker pressure monitor and placed on the volar wrist. Pressure was applied to
      the bag with a linear transducer and the radial artery was observed for
      coaptation of the anterior and posterior walls and complete collapse. Pressures
      required for coaptation and collapse were recorded from the Stryker display.
      Patient level of comfort was also documented during the URAC method, with
      patients reporting either "more," "same" or "less" comfort in comparison to
      automated cuffs. We analyzed data using intraclass correlation and paired t
      tests. Interrater reliability was calculated using intraclass correlation.
      RESULTS: The mean cuff systolic BP was 138.6 +/- 22.1 mmHg compared to 126.9 +/-
      19.8 mmHg for the URAC systolic BP (p=0.02). For diastolic BP, there was no
      significant difference between the cuff BP and the URAC BP (83.7 +/- 13.0 cuff
      vs. 86.5 +/- 19.8 URAC, p=0.46). The intraclass correlation (ICC) for systolic BP
      was 0.48 (p=0.04) and 0.57 (p=0.02) for diastolic BP. The agreement between the
      two observers was 0.88 for identifying coaptation on ultrasound (diastolic
      pressure) and was 0.92 for identifying collapse (systolic pressure). Eighty
      percent (20/25) of subjects found the URAC method more comfortable than the cuff
      measurement, and the remainder found it the same (5/20). CONCLUSION: This pilot
      study showed statistically significant moderate correlation between automated
      cuff diastolic BP and URAC measurements for vessel coaptation. Additionally, most
      patients found the URAC method more comfortable than traditional cuff
      measurements. Compression ultrasonography shows promise as an alternative method
      of BP measurement, though future studies are needed.

PMID- 28435504
TI  - Differentiating Urgent and Emergent Causes of Acute Red Eye for the Emergency
      Physician.
AB  - Patients commonly present with an acute red eye to the emergency department (ED).
      It is important to distinguish between benign and sight-threatening diagnoses.
      Here we provide a comprehensive overview on the acute red eye in the ED.

PMID- 28435505
TI  - Inter-rater Agreement of End-of-shift Evaluations Based on a Single Encounter.
AB  - INTRODUCTION: End-of-shift evaluation (ESE) forms, also known as daily encounter
      cards, represent a subset of encounter-based assessment forms. Encounter cards
      have become prevalent for formative evaluation, with some suggesting a potential
      for summative evaluation. Our objective was to evaluate the inter-rater agreement
      of ESE forms using a single scripted encounter at a conference of emergency
      medicine (EM) educators. METHODS: Following institutional review board exemption,
      we created a scripted video simulating an encounter between an intern and a
      patient with an ankle injury. That video was shown during a lecture at the
      Council of EM Residency Director's Academic Assembly with attendees asked to
      evaluate the "resident" using one of eight possible ESE forms randomly
      distributed. Descriptive statistics were used to analyze the results with Fleiss'
      kappa to evaluate inter-rater agreement. RESULTS: Most of the 324 respondents
      were leadership in residency programs (66%), with a range of 29-47 responses per
      evaluation form. Few individuals (5%) felt they were experts in assessing
      residents based on EM milestones. Fleiss' kappa ranged from 0.157 - 0.308 and did
      not perform much better in two post-hoc subgroup analyses. CONCLUSION: The kappa
      ranges found show only slight to fair inter-rater agreement and raise concerns
      about the use of ESE forms in assessment of EM residents. Despite limitations
      present in this study, these results and a lack of other studies on inter-rater
      agreement of encounter cards should prompt further studies of such methods of
      assessment. Additionally, EM educators should focus research on methods to
      improve inter-rater agreement of ESE forms or other evaluating other methods of
      assessment of EM residents.

PMID- 28435507
TI  - Blog and Podcast Watch: Orthopedic Emergencies.
AB  - INTRODUCTION: The WestJEM Blog and Podcast Watch presents high quality open
      access educational blogs and podcasts in emergency medicine (EM) based on the
      ongoing ALiEM Approved Instructional Resources (AIR) and AIR-Professional series.
      Both series critically appraise resources using an objective scoring rubric. This
      installment of the Blog and Podcast Watch highlights the topic of orthopedic
      emergencies from the AIR series. METHODS: The AIR series is a continuously
      building curriculum that follows the Council of Emergency Medicine Residency
      Directors (CORD) annual testing schedule. For each module, relevant content is
      collected from the top 50 Social Media Index sites published within the previous
      12 months, and scored by eight AIR board members using five equally weighted
      measurement outcomes: Best Evidence in Emergency Medicine (BEEM) score, accuracy,
      educational utility, evidence based, and references. Resources scoring >=30 out
      of 35 available points receive an AIR label. Resources scoring 27-29 receive an
      honorable mention label, if the executive board agrees that the post is accurate
      and educationally valuable. RESULTS: A total of 87 blog posts and podcasts were
      evaluated. Key educational pearls from the three AIR posts and the 14 honorable
      mentions are summarized. CONCLUSION: The WestJEM Blog and Podcast Watch series is
      based on the AIR and AIR-Pro series, which attempts to identify high quality
      educational content on open-access blogs and podcasts. This series provides an
      expert-based, post-publication curation of educational social media content for
      EM clinicians with this installment focusing on orthopedic emergencies.

PMID- 28435506
TI  - Audience Response System Facilitates Prediction of Scores on In-Training
      Examination.
AB  - INTRODUCTION: Audience response systems (ARS) are increasingly popular; however,
      their contribution to education is not completely clear. Our study found that
      scores from review quizzes delivered by an ARS correlate with in-training exam
      (ITE) scores and are viewed positively by residents. This information may be
      useful in identifying poor performers early so that targeted educational
      interventions can be made. The objective was to determine if scores on review
      quizzes delivered by an ARS correlate with ITE scores and to obtain participant
      feedback on use of the ARS for ITE preparation. METHODS: This was a prospective
      observational study of emergency medicine (EM) residents at six accredited EM
      residency programs. Subjects included residents who had taken previous ITEs.
      Subjects participated in bimonthly review sessions using an ARS. Twelve review
      quizzes were administered, each consisting of 10 multiple-choice questions. After
      the ITE, subjects completed an attitudinal survey consisting of six Likert-scale
      items and one "yes/no" item. We used a mixed linear model to analyze the data,
      accounting for prior 2012 ITE scores and nesting due to institution. RESULTS:
      Among 192 participants, 135 (70.3%) completed the ITE in both 2012 and 2013; we
      analyzed their data for the first objective. Results from the mixed linear model
      indicate that the total mean score on the review quizzes was a significant
      [t(127) = 6.68; p < 0.001] predictor of the 2013 ITE after controlling for the
      2012 ITE score. One hundred forty-six (76.0%) participants completed the
      attitudinal survey; 96% of respondents stated that they would like ARS to be used
      more often in resident education. Respondents felt the sessions aided in learning
      (mean 7.7/10), assisted in preparation for the ITE (mean 6.7/10), and helped
      identify content areas of weakness (mean 7.6/10). CONCLUSION: Our results suggest
      that scores from review quizzes delivered by an audience response system
      correlate with in-training exam scores and is viewed positively by residents.

PMID- 28435508
TI  - A Novel Collaboration to Reduce the Travel-Related Cost of Residency
      Interviewing.
AB  - INTRODUCTION: Interviewing for residency is a complicated and often expensive
      endeavor. Literature has estimated interview costs of $4,000 to $15,000 per
      applicant, mostly attributable to travel and lodging. The authors sought to
      reduce these costs and improve the applicant interview experience by coordinating
      interview dates between two residency programs in Chicago, Illinois. METHODS: Two
      emergency medicine residency programs scheduled contiguous interview dates for
      the 2015-2016 interview season. We used a survey to assess applicant experiences
      interviewing in Chicago and attitudes regarding coordinated scheduling. Data on
      utilization of coordinated dates were obtained from interview scheduling
      software. The target group for this intervention consisted of applicants from
      medical schools outside Illinois who completed interviews at both programs.
      RESULTS: Of the 158 applicants invited to both programs, 84 (53%) responded to
      the survey. Scheduling data were available for all applicants. The total
      estimated cost savings for target applicants coordinating interview dates was
      $13,950. The majority of target applicants reported that this intervention
      increased the ease of scheduling (84%), made them less likely to cancel the
      interview (82%), and saved them money (71%). CONCLUSION: Coordinated scheduling
      of interview dates was associated with significant estimated cost savings and was
      reviewed favorably by applicants across all measures of experience. Expanding use
      of this practice geographically and across specialties may further reduce the
      cost of interviewing for applicants.

PMID- 28435509
TI  - USMLE Scores Predict Success in ABEM Initial Certification: A Multicenter Study.
AB  - INTRODUCTION: There are no existing data on whether performance on the United
      States Medical Licensing Examination (USMLE) predicts success in American Board
      of Emergency Medicine (ABEM) certification. The aim of this study was to
      determine the presence of any association between USMLE scores and first-time
      success on the ABEM qualifying and oral certification examinations. METHODS: We
      retrospectively collected USMLE Step 1, Step 2 Clinical Knowledge (CK) scores and
      pass/fail results from the first attempt at ABEM qualifying and oral examinations
      from residents graduating between 2009 and 2011 from nine EM programs. A
      composite score was defined as the sum of USMLE Step 1 and Step 2 CK scores.
      RESULTS: Sample was composed of 197 residents. Median Step 1, Step 2 CK and
      composite scores were 218 ([IQR] 207-232), 228 (IQR 217-239) and 444 (IQR 427
      468). First-time pass rates were 95% for the qualifying examination and 93% for
      both parts of the examination. Step 2 CK and composite scores were better
      predictors of achieving ABEM initial certification compared to Step 1 score (area
      under the curve 0.800, 0.759 and 0.656). Step 1 score of 227, Step 2 CK score of
      225 and composite score of 444 predicted a 95% chance of passing both boards.
      CONCLUSION: Higher USMLE Step 1, Step 2 CK and composite scores are associated
      with better performance on ABEM examinations, with Step 2 CK being the strongest
      predictor. Cutoff scores for USMLE Step 1, Step 2 CK and composite score were
      established to predict first-time success on ABEM initial certification.

PMID- 28435511
TI  - A Statistical Model for Event Sequence Data.
AB  - The identification of recurring patterns within a sequence of events is an
      important task in behavior research. In this paper, we consider a general
      probabilistic framework for identifying such patterns, by distinguishing between
      events that belong to a pattern and events that occur as part of background
      processes. The event processes, both for background events and events that are
      part of recurring patterns, are modeled as competing renewal processes. Using
      this framework, we develop an inference procedure to detect the sequences present
      in observed data. Our method is compared to a current approach used within the
      ethology literature on both simulated data and data collected to study the impact
      of fragmented and unpredictable maternal behavior on cognitive development of
      children.

PMID- 28435510
TI  - Erratum: This Article Corrects: "Trends in NRMP Data from 2007-2014 for U.S.
      Seniors Matching into Emergency Medicine".
AB  - [This corrects the article on p. 105 in vol. 18, PMID: 28116018.].

PMID- 28435512
TI  - Linear mixed models for multiple outcomes using extended multivariate skew-t
      distributions.
AB  - Multivariate outcomes with heavy skewness and thick tails often arise from
      clustered experiments or longitudinal studies. Linear mixed models with
      multivariate skew-t (MST) distributions for the random effects and the error
      terms is a popular tool of robust modeling for such outcomes. However the usual
      MST distribution only allows a common degree of freedom for all marginal
      distributions, which is only appropriate when each marginal has the same amount
      of tail heaviness. In this paper, we introduce a new class of extended MST
      distributions, which allow different degrees of freedom and thereby can
      accommodate heterogeneity in tail-heaviness across outcomes. The extended MST
      distributions yield a flexible family of models for multivariate outcomes. The
      hierarchical representation of the MST distribution allows MCMC methods to be
      easily applied to compute the parameter estimates. The proposed model is applied
      to data from two biomedical studies: one on bivariate markers of AIDS progression
      and the other on sexual behavior from a longitudinal study.

PMID- 28435513
TI  - Pathways from Religion to Health: Mediation by Psychosocial and Lifestyle
      Mechanisms.
AB  - Religiosity, often measured as attendance at religious services, is linked to
      better physical health and longevity though the mechanisms linking the two are
      debated. Potential explanations include: a healthier lifestyle, increased social
      support from congregational members, and/or more positive emotions. Thus far,
      these mechanisms have not been tested simultaneously in a single model though
      they likely operate synergistically. We test this model predicting all-cause
      mortality in Seventh-day Adventists, a denomination that explicitly promotes a
      healthy lifestyle. This allows the more explicit health behaviors linked to the
      religious doctrine (e.g., healthy diet) to be compared with other mechanisms not
      specific to religious doctrine (e.g., social support and positive emotions).
      Finally, this study examines both Church Activity (including worship attendance
      and church responsibilities) and Religious Engagement (coping, importance, and
      intrinsic beliefs). Religious Engagement is more is more inner-process focused
      (vs. activity-based) and less likely to be confounded with age and its associated
      functional status limitations, although it should be noted that age is controlled
      in the present study. The findings suggest that Religious Engagement and Church
      Activity operate through the mediators of health behavior, emotion, and social
      support to decrease mortality risk. All links between Religious Engagement and
      mortality are positive but indirect through positive Religious Support,
      Emotionality, and lifestyle mediators. However, Church Activity has a direct
      positive effect on mortality as well as indirect effects through, Religious
      Support, Emotionality, and lifestyle mediators (diet and exercise). The models
      were invariant by gender and for both Blacks and Whites.

PMID- 28435514
TI  - AUTOMATIC MUSCLE PERIMYSIUM ANNOTATION USING DEEP CONVOLUTIONAL NEURAL NETWORK.
AB  - Diseased skeletal muscle expresses mononuclear cell infiltration in the regions
      of perimysium. Accurate annotation or segmentation of perimysium can help
      biologists and clinicians to determine individualized patient treatment and allow
      for reasonable prognostication. However, manual perimysium annotation is time
      consuming and prone to inter-observer variations. Meanwhile, the presence of
      ambiguous patterns in muscle images significantly challenge many traditional
      automatic annotation algorithms. In this paper, we propose an automatic
      perimysium annotation algorithm based on deep convolutional neural network (CNN).
      We formulate the automatic annotation of perimysium in muscle images as a pixel
      wise classification problem, and the CNN is trained to label each image pixel
      with raw RGB values of the patch centered at the pixel. The algorithm is applied
      to 82 diseased skeletal muscle images. We have achieved an average precision of
      94% on the test dataset.

PMID- 28435515
TI  - Using Outcomes to Analyze Patients Rather than Patients to Analyze Outcomes: A
      Step toward Pragmatism in Benefit:risk Evaluation.
AB  - In the future, clinical trials will have an increased emphasis on pragmatism,
      providing a practical description of the effects of new treatments in realistic
      clinical settings. Accomplishing pragmatism requires better summaries of the
      totality of the evidence in ways that clinical trials consumers---patients,
      physicians, insurers---find transparent and allow for informed benefit:risk
      decision-making. The current approach to the analysis of clinical trials is to
      analyze efficacy and safety separately and then combine these analyses into a
      benefit:risk assessment. Many assume that this will effectively describe the
      impact on patients. But this approach is suboptimal for evaluating the totality
      of effects on patients. We discuss methods for benefit:risk assessment that have
      greater pragmatism than methods that separately analyze efficacy and safety.
      These include the concepts of within-patient analyses and composite benefit:risk
      endpoints with a goal of understanding how to analyze one patient before trying
      to figure out how to analyze many. We discuss the desirability of outcome ranking
      (DOOR) and introduce the partial credit strategy using an example in a clinical
      trial evaluating the effects of a new antibiotic. As part of the example we
      introduce a strategy to engage patients as a resource to inform benefit:risk
      analyses consistent with the goal of measuring and weighing outcomes that are
      most important from the patient's perspective. We describe a broad vision for the
      future of clinical trials consistent with increased pragmatism. Greater focus on
      using endpoints to analyze patients rather than patients to analyze endpoints
      particularly in late-phase/stage clinical trials is an important part of this
      vision.

PMID- 28435516
TI  - Docosahexaenoic acid (DHA) promotes immunogenic apoptosis in human multiple
      myeloma cells, induces autophagy and inhibits STAT3 in both tumor and dendritic
      cells.
AB  - Docosahexaenoic acid (DHA), a omega-3 polyunsaturated fatty acid found in fish
      oil, is a multi-target agent and exerts anti-inflammatory and anticancer
      activities alone or in combination with chemotherapies. Combinatorial anticancer
      therapies, which induce immunogenic apoptosis, autophagy and STAT3 inhibition
      have been proposed for long-term therapeutic success. Here, we found that DHA
      promoted immunogenic apoptosis in multiple myeloma (MM) cells, with no toxicity
      on PBMCs and DCs. Immunogenic apoptosis was shown by the emission of specific
      DAMPs (CRT, HSP90, HMGB1) by apoptotic MM cells and the activation of their pro
      apoptotic autophagy. Moreover, immunogenic apoptosis was directly shown by the
      activation of DCs by DHA-induced apoptotic MM cells. Furthermore, we provided the
      first evidence that DHA activated autophagy in PBMCs and DCs, thus potentially
      acting as immune stimulator and enhancing processing and presentation of tumor
      antigens by DCs. Finally, we found that DHA inhibited STAT3 in MM cells. STAT3
      pathway, essential for MM survival, contributed to cancer cell apoptosis by DHA.
      We also found that DHA inhibited STAT3 in blood immune cells and counteracted
      STAT3 activation by tumor cell-released factors in PBMCs and DCs, suggesting the
      potential enhancement of the anti-tumor function of multiple immune cells and, in
      particular, that of DCs.

PMID- 28435517
TI  - Inhibition of the platelet-derived growth factor receptor beta (PDGFRB) using
      gene silencing, crenolanib besylate, or imatinib mesylate hampers the malignant
      phenotype of mesothelioma cell lines.
AB  - Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity resistant
      to chemotherapy. The identification of novel therapeutic targets is needed to
      improve its poor prognosis. Following a review of literature and a screening of
      specimens we found that platelet-derived growth factor receptor beta (PDGFRB) is
      over-expressed, but not somatically mutated, in MPM tissues. We aimed to
      ascertain whether PDGFRB is a MPM-cancer driver gene. The approaches employed
      included the use of gene silencing and the administration of small molecules,
      such as crenolanib and imatinib (PDGFR inhibitors) on MPM cell lines (IstMes2,
      Mero-14, Mero-25). Met5A cells were used as non-malignant mesothelial cell line.
      PDGFRB-silencing caused a decrease in the proliferation rate, and a reduced
      colony formation capacity, as well as an increase of the share of cells in sub-G1
      and in G2 phase, and increased apoptotic rate of MPM cell lines. Loss of
      migration ability was also observed. Similar, or even further enhanced, results
      were obtained with crenolanib. Imatinib showed the least effective activity on
      the phenotype. In conclusion, our study highlights PDGFRB as target with a clear
      role in MPM tumorigenesis and provided a rationale to explore further the
      efficacy of crenolanib in MPM patients, with promising results.

PMID- 28435518
TI  - SPARC overexpression alters microRNA expression profiles involved in tumor
      progression.
AB  - Medulloblastoma is the most common malignant brain tumor in children. SPARC
      (secreted protein acidic and rich in cysteine), a multicellular non-structural
      glycoprotein is known to be involved in multiple processes in various cancers.
      Previously, we reported that SPARC expression significantly impairs
      medulloblastoma tumor growth in vitro and in vivo and also alters chemo
      sensitivity. MicroRNAs are a class of post-transcriptional gene regulators with
      critical functions in tumor progression. In addition, microRNA (miRNA) expression
      changes are also involved in chemo-resistance. Herein, we assessed microRNA
      (miRNA) profiling to identify the functional network and biological pathways
      altered in SPARC-overexpressed medulloblastoma cells. A total of 27
      differentially expressed miRNAs were identified between the control and SPARC
      overexpressed samples. Potential messenger RNA (mRNA) targets of the
      differentially expressed miRNA were identified using Ingenuity Pathway Analysis
      (IPA). Network-based functional analyses were performed on the available human
      protein interaction and miRNA-gene association data to highlight versatile miRNAs
      among the significantly deregulated miRNAs using the IPA, and the biological
      pathway analysis using the PANTHER web-based tool. We have identified six miRNAs
      (miR-125b1*, miR-146a-5p, miR-181a-5p, miR-204-5p, miR-219-5p and miR-509-3p)
      that are associated with SPARC sensitivity by comparison of miRNA expression
      patterns from the SPARC treated cells with the control cells. Furthermore,
      pathway enrichment analysis outline that these six microRNAs mainly belong to
      biological processes related to cancer related signaling pathways. Collectively,
      these studies have the potential to indicate novel biomarkers for treatment
      response and can also be applied to develop novel therapeutic treatment for
      medulloblastoma.

PMID- 28435519
TI  - GT198 (PSMC3IP) germline variants in early-onset breast cancer patients from
      hereditary breast and ovarian cancer families.
AB  - GT198, located 470 kb downstream of BRCA1, encodes for the nuclear PSMC3
      interacting protein, which functions as co-activator of steroid hormone-mediated
      gene expression, and is involved in RAD51 and DMC1-mediated homologous
      recombination during DNA repair of double-strand breaks. Recently, germline
      variants in GT198 have been identified in hereditary breast and ovarian cancer
      (HBOC) patients, mainly in cases with early-onset. We screened a cohort of 166
      BRCA1/2 mutation-negative HBOC patients, of which 56 developed early-onset breast
      cancer before the age of 36 years, for GT198 variants. We identified 7 novel or
      rare GT198 variants in 8 out of 166 index patients: c.-115G>A (rs191843707); c.
      70T>A (rs752276800); c.-37A>T (rs199620968); c.-24C>G (rs200359709); c.519G>A
      p.(Trp173*); c.537+51G>C (rs375509656); c.*24G>A. Three out of 7 identified
      variants (c.-115G>A, c.519G>A and c.*24G>A) with putative pathogenic impact were
      found in HBOC patients with breast cancer onset at <= 36 years. The nonsense
      mutation c.519G>A p.(Trp173*) was located within the DNA binding domain of GT198
      and is predicted to induce nonsense-mediated mRNA decay. Functional analyses of
      c.-115G>A, and c.*24A>G indicated an influence of these variants on gene
      expression. This is the second study that gives evidence for an association
      between pathogenic GT198 germline variants and early-onset breast cancer in HBOC.

PMID- 28435520
TI  - Genetically transforming human osteoblasts to sarcoma: development of an
      osteosarcoma model.
AB  - Osteosarcoma is the most common primary malignant bone tumor in children and
      young adults. Although histologically defined by the presence of malignant
      osteoid, the tumor possesses lineage multipotency suggesting it could be derived
      from a cell anywhere on the differentiation pathway between a mesenchymal stem
      cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be
      the cell of origin differentiated MSCs were transformed with defined genetic
      elements. MSCs and pOB differentiated from the same MSCs were serially
      transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras. Assays were
      performed to determine their tumorigenic properties, differentiation capacity and
      histologic appearance. When subcutaneously implanted in immunocompromised mice,
      cell lines derived from transformed MSC and pOB formed tumors in 4 weeks. In
      contrast to the transformed MSC, the pOB tumors demonstrated a histological
      appearance characteristic of osteosarcoma. The cell lines derived from the
      transformed pOB only had osteogenic and chondrogenic differentiation potential,
      but not adipogenic ones. However, the transformed MSC cells and standard
      osteosarcoma cell lines maintained their tri-lineage differentiation capacity.
      The inability of the transformed pOB cell line to undergo adipogenic
      differentiation, may suggest that osteosarcoma is derived from a cell
      intermediate in differentiation between an MSC and a pOB, with partial commitment
      to the osteoblastic lineage.

PMID- 28435521
TI  - Intracardiac Echocardiographic Atrial Septal Defect Closure.
AB  - Intracardiac echocardiography (ICE) is an excellent ultrasound modality that can
      be used to guide atrial septal defect (ASD) closure. Compared with
      transesophageal echocardiography, ICE offers better imaging of the posterior
      inferior septum, it does not require deep or general anesthesia, and it allows
      the operator total control over image acquisition. This latter advantage requires
      that the operator become an expert in image acquisition and interpretation. The
      following is intended to serve as a primer on performance and interpretation of
      ICE to guide ASD closure.

PMID- 28435522
TI  - The Ecstasy and Agony of Assay Interference Compounds.

PMID- 28435524
TI  - Pyrano[2,3,4-cd]indole as a Scaffold for Selective Nonbasic 5-HT6R Ligands.
AB  - In this letter, we report the synthesis of a pyrano[2,3,4-cd]indole chemical
      scaffold designed through a tandem bioisostere generation/virtual screening
      protocol in search of 5-HT6R ligands. The discovered chemical scaffold resulted
      in the design of highly active basic and nonbasic 5-HT6R ligands (5-HT6R Ki = 1
      nM for basic compound 6b and 5-HT6R Ki = 4 nM for its neutral analog 7b).
      Additionally, molecular modeling suggested that the hydroxyl group of nonbasic
      ligands 7a-7d forms hydrogen bonds with aspartic acid D3*32 or D7.36*35.

PMID- 28435523
TI  - Discovery of [1,2,3]Triazolo[4,5-d]pyrimidine Derivatives as Novel LSD1
      Inhibitors.
AB  - Lysine specific demethylase 1 (LSD1) plays a pivotal role in regulating the
      lysine methylation. The aberrant overexpression of LSD1 has been reported to be
      involved in the progression of certain human malignant tumors. Abrogation of LSD1
      with RNAi or small molecule inhibitors may lead to the inhibition of cancer
      proliferation and migration. Herein, a series of [1,2,3]triazolo[4,5-d]pyrimidine
      derivatives were synthesized and evaluated for their LSD1 inhibitory effects. The
      structure-activity relationship studies (SARs) were conducted by exploring three
      regions of this scaffold, leading to the discovery of compound 27 as potent LSD1
      inhibitor (IC50 = 0.564 MUM). Compound 27 was identified as a reversible LSD1
      inhibitor and showed certain selectivity to LSD1 over monoamine oxidase A/B (MAO
      A/B). When MGC-803 cells were treated with compound 27, the activity of LSD1 can
      be significantly inhibited, and the cell migration ability was also suppressed.
      Docking studies indicated that the hydrogen interaction between the nitrogen atom
      in the pyridine ring and Met332 could be responsible for the improved activity of
      2-thiopyridine series. The [1,2,3]triazolo[4,5-d]pyrimidine scaffold can be used
      as the template for designing new LSD1 inhibitors.

PMID- 28435525
TI  - Development and Biological Evaluation of a Photoactivatable Small Molecule
      Microtubule-Targeting Agent.
AB  - Photoremovable protecting groups added to bioactive molecules provide spatial and
      temporal control of the biological effects. We present synthesis and
      characterization of the first photoactivatable small-molecule tubulin inhibitor.
      By blocking the pharmacophoric OH group on compound 1 with photoremovable 4,5
      dimethoxy-2-nitrobenzyl moiety we developed the photocaged prodrug 2 that had no
      effect in biological assays. Short UV light exposure of the derivative 2 or UV
      irradiation of cells treated with 2 resulted in fast and potent inhibition of
      tubulin polymerization, attenuation of cell viability, and apoptotic cell death,
      implicating release of the parent active compound. This study validates for the
      first time the photoactivatable prodrug concept in the field of small molecule
      tubulin inhibitors. The caged derivative 2 represents a novel tool in antitubulin
      approaches.

PMID- 28435526
TI  - RITA Mimics: Synthesis and Mechanistic Evaluation of Asymmetric Linked
      Trithiazoles.
AB  - The established cytotoxic agent RITA contains a thiophene-furan-thiophene
      backbone and two terminal alcohol groups. Herein we investigate the effect of
      using thiazoles as the backbone in RITA-like molecules and modifying the terminal
      groups of these trithiazoles, thereby generating 41 unique structures.
      Incorporating side chains with varied steric bulk allowed us to investigate how
      size and a stereocenter impacted biological activity. Subjecting compounds to
      growth inhibition assays on HCT-116 cells showed that the most potent compounds
      7d, 7e, and 7h had GI50 values of 4.4, 4.4, and 3.4 MUM, respectively, versus
      RITA (GI50 of 800 nM). Analysis of these compounds in apoptosis assays proved
      that 7d, 7e, and 7h were as effective as RITA at inducing apoptosis. Evaluating
      the impact of 7h on proteins targeted by RITA (p53, c-Myc, and Mcl-1) indicated
      that it acts via a different mechanism of action to that of RITA. RITA suppressed
      Mcl-1 protein via p53, whereas compound 7h suppressed Mcl-1 expression via an
      alternative mechanism independent of p53.

PMID- 28435527
TI  - Discovery of Highly Potent 2-Sulfonyl-Pyrimidinyl Derivatives for Apoptosis
      Inhibition and Ischemia Treatment.
AB  - A series of 2-sulfonyl-pyrimidinyl derivatives was developed as apoptosis
      inhibitors. These represent the first class of apoptosis inhibitors that function
      through stabilizing mitochondrial respiratory complex II. Starting from a
      phenotypic screen hit with micromolar activity, we optimized the cellular
      apoptosis inhibition activity of 2-sulfonyl-pyrimidinyl derivatives to picomolar
      level (compound 42, also named as TC9-305). The therapeutic potential of these
      new apoptosis inhibitors was further demonstrated by their neuroprotective effect
      on an ischemic animal model.

PMID- 28435528
TI  - Discovery of Highly Selective Inhibitors of the Immunoproteasome Low Molecular
      Mass Polypeptide 2 (LMP2) Subunit.
AB  - Building upon the success of bortezomib (VELCADE) and carfilzomib (KYPROLIS), the
      design of a next generation of inhibitors targeting specific subunits within the
      immunoproteasome is of interest for the treatment of autoimmune disease. There
      are three catalytic subunits within the immunoproteasome (low molecular mass
      polypeptide-7, -2, and multicatalytic endopeptidase complex subunit-1; LMP7,
      LMP2, and MECL-1), and a campaign was undertaken to design a potent and selective
      LMP2 inhibitor with sufficient properties to allow for sustained inhibition in
      vivo. Screening a focused library of epoxyketones revealed a series of potent
      dipeptides that were optimized to provide the highly selective inhibitor KZR-504
      (12).

PMID- 28435529
TI  - 18F-Labeled Pyrido[3,4-d]pyrimidine as an Effective Probe for Imaging of L858R
      Mutant Epidermal Growth Factor Receptor.
AB  - In nonsmall-cell lung carcinoma patients, L858R mutation of epidermal growth
      factor receptor (EGFR) is often found, and molecular target therapy using EGFR
      tyrosine kinase inhibitors is effective for the patients. However, the treatment
      frequently develops drug resistance by secondary mutation, of which approximately
      50% is T790M mutation. Therefore, the ability to predict whether EGFR will
      undergo secondary mutation is extremely important. We synthesized a novel
      radiofluorinated 4-(anilino)pyrido[3,4-d]pyrimidine derivative ([18F]APP-1) and
      evaluated its potential as a positron emission tomography (PET) imaging probe to
      discriminate the difference in mutations of tumors. EGFR inhibition assay, cell
      uptake, and biodistribution study showed that [18F]APP-1 binds specifically to
      the L858R mutant EGFR but not to the L858R/T790M mutant. Finally, on PET imaging
      study using [18F]APP-1 with tumor-bearing mice, the H3255 tumor (L858R mutant)
      was more clearly visualized than the H1975 tumor (L858R/T790M mutant).

PMID- 28435531
TI  - Discovery of the First Environment-Sensitive Fluorescent Probe for GPR120 (FFA4)
      Imaging.
AB  - GPR120, which is activated by long-chain free fatty acids (FFAs), has been
      recognized as a new attractive target for the treatment of type 2 diabetes and
      metabolic disease. The visualization and location of GPR120 in native cells can
      provide powerful information for guiding the physiological and pathological
      studies of GPR120. We report herein the first potent fluorescent probes that
      sensitively detect GPR120. We designed and synthesized a series of novel
      environment-sensitive probes with suitable fluorescence property, high biological
      activity on the GPR120, and acceptable cytotoxicity. These fluorescent probes
      targeting GPR120 are expected to expand the toolkit for further studies on
      GPR120.

PMID- 28435530
TI  - Small Molecule Lysyl Oxidase-like 2 (LOXL2) Inhibitors: The Identification of an
      Inhibitor Selective for LOXL2 over LOX.
AB  - Two series of novel LOXL2 enzyme inhibitors are described: benzylamines
      substituted with electron withdrawing groups at the para-position and 2
      substituted pyridine-4-ylmethanamines. The most potent compound, (2-chloropyridin
      4-yl)methanamine 20 (hLOXL2 IC50 = 126 nM), was shown to be selective for LOXL2
      over LOX and three other amine oxidases (MAO-A, MAO-B, and SSAO). Compound 20 is
      the first published small molecule inhibitor selective for LOXL2 over LOX.

PMID- 28435532
TI  - X-ray Structure of the Carboplatin-Loaded Apo-Ferritin Nanocage.
AB  - The second-generation Pt anticancer agent carboplatin (CBDCA) was encapsulated
      within the apo horse spleen ferritin (AFt) nanocage, and the X-ray structure of
      the drug-loaded protein was refined at 1.49 A resolution. Two Pt binding sites,
      different from the one observed in the cisplatin-encapsulated AFt, were
      identified in Ft subunits by inspection of anomalous electron density maps at two
      wavelengths and difference Fourier electron density maps, which provide the
      necessary sensitivity to discriminate between Pt from CBDCA and Cd ions that are
      present in the crystallization conditions. Pt centers coordinate to the NE2 atom
      of His49 and to the NE2 atom of His132, both on the inner surface of the Ft
      nanocage.

PMID- 28435533
TI  - Discovery of Antimalarial Azetidine-2-carbonitriles That Inhibit P. falciparum
      Dihydroorotate Dehydrogenase.
AB  - Dihydroorotate dehydrogenase (DHODH) is an enzyme necessary for pyrimidine
      biosynthesis in protozoan parasites of the genus Plasmodium, the causative agents
      of malaria. We recently reported the identification of novel compounds derived
      from diversity-oriented synthesis with activity in multiple stages of the malaria
      parasite life cycle. Here, we report the optimization of a potent series of
      antimalarial inhibitors consisting of azetidine-2-carbonitriles, which we had
      previously shown to target P. falciparum DHODH in a biochemical assay. Optimized
      compound BRD9185 (27) has in vitro activity against multidrug-resistant blood
      stage parasites (EC50 = 0.016 MUM) and is curative after just three doses in a P.
      berghei mouse model. BRD9185 has a long half-life (15 h) and low clearance in
      mice and represents a new structural class of DHODH inhibitors with potential as
      antimalarial drugs.

PMID- 28435534
TI  - Antioxidant Properties of Novel Dimers Derived from Natural beta-Elemene through
      Inhibiting H2O2-Induced Apoptosis.
AB  - A series of novel beta-elemene dimer derivatives were synthesized and evaluated
      for their antioxidant activities. The results indicated that most of the target
      compounds showed more potent cytoprotective effects than positive control vitamin
      E. In particular, dimer D5 exhibited the strongest antioxidant activity, which
      was significantly superior to the active compound D1 obtained in our previous
      study. Besides, D5 did not produce obvious cytotoxicity in normal human umbilical
      vein endothelial cells (HUVECs) and increased the viability of HUVECs injured by
      H2O2 in a concentration-dependent manner. Further studies suggested that the
      cytoprotective action of D5 might be mediated, at least in part, by increasing
      the intracellular superoxide dismutase activity and nitric oxide secretion as
      well as decreasing the intracellular malonyldialdehyde content and lactate
      dehydrogenase release. Furthermore, D5 observably inhibited ROS generation and
      prevented H2O2-induced apoptosis in HUVECs possibly via inhibiting the activation
      of the MAPK signaling pathway.

PMID- 28435535
TI  - Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues
      Containing a Xylene Bridge.
AB  - d-Pen2,d-Pen5 enkephalin (DPDPE) is one of the most selective synthetic peptide
      agonists targeting the delta-opioid receptor. Three cyclic analogues of DPDPE
      containing a xylene bridge in place of disulfide bond have been synthesized and
      fully characterized as opioid receptors agonists. The in vitro activity was
      investigated showing a good affinity of 7a-c for MU- and delta-receptors. In vivo
      biological assays revealed that 7b is the most potent analogue with the ability
      to maintain high level of analgesia from 15 to 60 min following
      intracerebroventricular (i.c.v.) administration, whereas DPDPE was slightly
      active until 45 min. Compound 7b induced long lasting analgesia also after
      subcutaneous administration, whereas DPDPE was inactive.

PMID- 28435536
TI  - Norbenzomorphan Scaffold: Chemical Tool for Modulating Sigma Receptor-Subtype
      Selectivity.
AB  - Some norbenzomorphans exhibit high affinity for sigma 1 and sigma 2 receptors,
      and varying the position of substituents on the aromatic ring of this scaffold
      has a significant effect on subtype selectivity. In particular, compounds bearing
      several different substituents at C7 of the norbenzomorphan ring system exhibit a
      general preference for the sigma 1 receptor, whereas the corresponding C8
      substituted analogues preferentially bind at the sigma 2 receptor. These findings
      suggest that the norbenzomorphan scaffold may be a unique chemical template that
      can be easily tuned to prepare small molecules for use as tool compounds to study
      the specific biological effects arising from preferential binding at either sigma
      receptor subtype. In the absence of structural characterization data for the
      sigma 2 receptor, such compounds will be useful toward refining the pharmacophore
      model of its binding site.

PMID- 28435537
TI  - Integrated Platform for Expedited Synthesis-Purification-Testing of Small
      Molecule Libraries.
AB  - The productivity of medicinal chemistry programs can be significantly increased
      through the introduction of automation, leading to shortened discovery cycle
      times. Herein, we describe a platform that consolidates synthesis, purification,
      quantitation, dissolution, and testing of small molecule libraries. The system
      was validated through the synthesis and testing of two libraries of binders of
      polycomb protein EED, and excellent correlation of obtained data with results
      generated through conventional approaches was observed. The fully automated and
      integrated platform enables batch-supported compound synthesis based on a broad
      array of chemical transformations with testing in a variety of biochemical assay
      formats. A library turnaround time of between 24 and 36 h was achieved, and
      notably, each library synthesis produces sufficient amounts of compounds for
      further evaluation in secondary assays thereby contributing significantly to the
      shortening of medicinal chemistry discovery cycles.

PMID- 28435538
TI  - Scaling Up a Multifaceted Violence Prevention Package: County-Level Impact of the
      North Carolina Youth Violence Prevention Center.
AB  - OBJECTIVE: Multifaceted approaches to youth-violence prevention package evidence
      based programs into initiatives that yield large-scale impact. This study
      assessed the impact of a package of evidence-based violence prevention programs,
      implemented as part of the North Carolina Youth Violence Prevention Center, on
      county-level violence indicators. METHOD: Using growth-curve modeling, the target
      county was compared to all other counties in North Carolina and a comparison
      county. RESULTS: Results reveal downward trends on several county-level
      indicators (i.e., undisciplined/delinquent complaints, total delinquent
      complaints, juvenile arrests-aggravated assaults, and short-term suspensions)
      throughout the intervention period. However, statistical tests were unable to
      confirm that intervention-period scores on youth-violence indicators were
      significantly different than expected scores given the relationship between
      pretest and intervention-period scores in other North Carolina counties.
      CONCLUSIONS: Although additional administrative data points are needed to support
      the hypotheses, this study provides preliminary evidence of the effectiveness of
      North Carolina Youth Violence Prevention Center interventions.

PMID- 28435539
TI  - Effectiveness of Serial Measurement of Differential Pressure in Closed Tibial
      Diaphyseal Fractures in Diagnosing Acute Compartment Syndrome using Whiteside's
      Technique.
AB  - Acute Compartment Syndrome is a limb-threatening emergency and it occurs most
      commonly after fractures. The aim of our study is to find out the effectiveness
      of serial measurement of differential pressure in closed tibial diaphyseal
      fractures, in diagnosing acute compartment syndrome, using Whiteside's technique.
      A total of 52 cases in the age group of 15 to 55 years admitted with closed
      fractures were studied for serial compartment pressure as well as serial
      differential pressure. Eight patients had persistent compartment pressure >
      40mmHg, out of which only two patients had persistent differential pressure <
      30mmHg and these two patients underwent fasciotomy. Thus, by measuring the
      compartment pressure serially and calculating differential pressure serially,
      acute compartment syndrome can be diagnosed or ruled out with higher precision,
      so that unnecessary fasciotomies can be avoided.

PMID- 28435540
TI  - Cemented Hemiarthroplasty in Elderly Osteoporotic Unstable Trochanteric Fractures
      using Fracture Window.
AB  - Introduction: We would like to analyze the role of cemented hemiarthroplasty in
      elderly osteoporotic unstable intertrochanteric fractures through trochanteric
      fracture window. Materials and Methods: The study was conducted from July 2011 to
      July 2014. From a total of 265 consecutive patients with intertrochanteric
      fractures of 42 patients were selected according to inclusion criteria and
      results were analyzed prospectively. All patients were operated at tertiary care
      institute. Patients which matched the inclusion criteria were selected. 42
      patients entered the study and all completed the study. Primary cemented
      hemiarthroplasty was done in all patients. Modified Harris Hip Score was used to
      assess all the patients. Results: 42 patients were included in the study with an
      average age of 80.7 years. Only AO/OTA type 31-A2.2 and 31-A2.3 were included,
      average HHS at final follow up of three years was 86.2. No revision or
      reoperation was done. Conclusion: In a selected cohort of patients primary
      prosthetic replacement in elderly osteoporotic unstable intertrochanteric
      fractures is good option and the surgical technique allowed us to perform it more
      easily.

PMID- 28435541
TI  - Analysis of Associated Spinal Fractures in Cases of Traumatic Intracranial
      Hemorrhage or Skull Fracture.
AB  - Introduction: Patients with traumatic intracranial hemorrhage (ICH) or skull
      fracture are typically admitted to the Department of Neurosurgery for fear of
      delayed neurological deterioration. Neurosurgeons, therefore, must be careful not
      to overlook a spinal fracture in these patients. In this study, we investigated
      the occurrence and risk factor of spinal fracture in patients with traumatic ICH
      or skull fracture. Patients and methods: We retrospectively analyzed the hospital
      records of 134 patients admitted to the Department of Neurosurgery at Kagawa
      Rosai Hospital for traumatic ICH or skull fracture. The etiology of trauma, level
      of consciousness, presence or absence of ICH, skull fracture, craniotomy and
      spinal surgery were investigated. Furthermore, in cases of spinal fracture, its
      type, neurological symptoms, treatment were investigated. Results: In an analysis
      of 134 patients, Ground level fall and traffic accident were the most frequent
      etiologies of trauma (47.0% and 23.9% respectively). Glasgow coma scale on
      admission was 15-13 for 106 patients (79.1%). spinal fracture was identified in
      10 of 134 patients (7.5%). Two patients had cervical, 8 had thoracolumbar
      fractures. In the analysis of risk factors, an accidental fall and skull fracture
      was observed significantly more in the spinal fracture cases. Conclusion: The
      majority of traumatic ICH or skull fracture cases treated in the Department of
      Neurosurgery were caused by minor head impacts. When treating these patients, it
      is necessary to investigate not only the cervical, but also the thoracolumbar
      spine, especially when the cause of injury is an accidental fall and a skull
      fracture is identified.

PMID- 28435542
TI  - The Outcome of Complex Pelvic Fracture after Internal Fixation Surgery.
AB  - Introduction: Complex pelvic fracture, which has a very high mortality and even
      higher morbidity, needs internal fixation surgery as an integral part for its
      management. It was necessary to conduct a study regarding outcome of complex
      pelvic fractures after internal fixation surgery. Material & Method: Twenty-six
      patients with complex pelvic fractures that had been treated with internal
      fixation surgery during 2011-2014 were enrolled. These patients had an open
      pelvic fractures or Tile type B or C pelvic fracture who had undergone internal
      fixation surgery with at least 6 months follow-up. Evaluation of the morbidity
      and functional scoring was performed using Majeed and Hannover Score. Results and
      Discussions: Average of age was 31 years old and follow up time was 25 months.
      There were 7 patients with open pelvic fracture and 19 with closed fracture.
      Excellent Majeed Score were found on 78.6% cases in Tile B fractures and 50% in
      Tile C. Good Hannover Score was found in 64.3% Tile B cases and 80% Tile C cases.
      Fracture type was statistically insignificant with acquired sexual dysfunction
      (p>0.05), but significant with the chronic pain (p=0,.017). We also found that
      urogenital injury is associated with sexual dysfunction (p=0.005). Conclusions:
      The outcome of complex pelvic fracture after internal fixation surgery was
      excellent. More than 90% patients got an excellent and good result on Majeed
      Score, and also very good and good result on Hannover Score.

PMID- 28435543
TI  - Comparison of Short vs Long Anti-rotation in Treating Trochanteric Fractures.
AB  - Introduction: A comparative evaluation of the surgical treatment and outcome of
      patients with pertrochanteric fractures treated with short versus long proximal
      femoral nail antirotation. Materials and methods: A retrospective review was
      conducted of patients with pertrochanteric fractures treated between January 2011
      and June 2012. In all 80 patients were enrolled in the study, of which 40 were
      treated with short PFNA and the remaining with long PFNA. Comparative analyses of
      demographic data, peri-operative outcome and complications were carried out.
      Results: There was no significant difference noted in the two groups with regards
      to Arbeitsgemeinschaft fur Osteosynthesefragen (AO) fracture classification, time
      from injury to surgery, blood transfusion post surgery and hospital stay. The
      surgical duration for a short PFNA procedure was significantly less (58 minutes)
      when compared to that of a long PFNA (87 minutes). Similarly intra-operative
      blood loss was significantly higher in the long PFNA group as compared to the
      short PFNA. Conclusions: A relatively quicker surgical time of just under an hour
      , lesser blood loss and better learning curve with trainee surgeons make short
      PFNA a better implant choice in the treatment of pertrochanteric fractures.

PMID- 28435544
TI  - Minimally Invasive Plate Osteosynthesis (MIPO) for Proximal and Distal Fractures
      of The Tibia: A Biological Approach.
AB  - Introduction: The treatment of fractures of proximal and distal tibia is
      challenging, because of the limited soft tissue envelope and poor vascularity.
      The best treatment remains controversial and it depends on the fracture
      morphology, displacement and comminution. Treatment options vary from closed
      reduction and cast to open reduction and internal fixation with plate. Open
      reduction and internal fixation with plate can result in extensive dissection and
      tissue devitalization. We conducted a study on management of these fractures by
      biological osteosynthesis using Minimally Invasive Plate Osteosynthesis (MIPO)
      technique with preservation of osseous and soft tissue vascularity. Methods: We
      conducted a prospective study on closed reduction and percutaneous plating in 30
      cases (mean age 42.7 years; 22 males and 8 females) of closed fractures of tibia.
      Among them 24 had proximal tibial fractures and 6 had distal tibial fractures.
      The mean time from injury to surgery was seven days. Results: The mean operative
      time was 72.6 minutes ( range: 55-90 minutes). Mean time for radiological union
      was 17 weeks (range: 14-22 weeks). There was one superficial wound infection
      which resolved with daily dressings and one week of oral antibiotics. One patient
      developed a nonunion which required a bone grafting procedure. Conclusions: The
      satisfactory functional results and lack of soft tissue complications suggest
      that this method should be considered in periarticular fractures. Biological
      fixation of complex fractures gives stable as well as optimal internal fixation
      and complete recovery of limb function at an early stage with minimal risk of
      complications.

PMID- 28435545
TI  - Treatment of Middle Third Humeral Shaft Fractures with Anteromedial Plate
      Osteosynthesis through an Anterolateral Approach.
AB  - Background: Treatment of humeral shaft fractures has been a subject of debate for
      many decades. Even though a large majority of humeral shaft fractures can be
      treated by non operative methods, few conditions like open fractures, polytrauma,
      ipsilateral humeral shaft and forearm fractures require surgical intervention.
      The goal of treatment of humeral shaft fractures is to establish union with an
      acceptable humeral alignment and to restore the patient to pre-injury level of
      function. The objective was to assess the incidence of radial nerve palsy, non
      union and mean time required for in anteromedial plate osteosynthesis with
      anterolateral approach and also to measure the functional outcome of this
      procedure. Method: A prospective study was conducted in the Department of
      Orthopaedics, PESIMSR, Kuppam, Andhra Pradesh, from August 2012 to August 2015
      with a total of 54 patients who were operated with anteromedial plate
      osteosynthesis were included in the study. Rodriguez- Merchan criteria was used
      to grade the functional outcome. Results: Of the 54 patients, 28 (58.85%) were in
      the age group of 30-40 years. The most common fracture pattern identified was A3
      type (48.14%).The mean (+/- SD) duration of surgery for anteromedial humeral
      plating was 53 +/- 5.00 minutes. The time taken for the fracture to unite was
      less than 16 weeks in the majority or 50 patients (92.59%). Four (7.40%) patients
      had delayed union. There was no incidence of iatrogenic radial nerve palsy.
      Rodriguez - Merchan criteria showed that 37(68.51%) of the patients had good and
      12 (22.22%) had excellent functional outcome.

PMID- 28435546
TI  - Outcomes of Paediatric Elbow Dislocations.
AB  - : Introduction: Elbow dislocations are uncommon in children. The treatment and
      outcomes remains controversial. MATERIALS AND METHODS: We report retrospectively
      the clinical and functional results of elbow dislocations in children treated in
      Sahloul University Hospital. Both isolated or pure dislocations and those
      associated with other injuries were evaluated separately. Results: Forty-eight
      children were selected based on inclusion criteria. All were unilateral injuries.
      Pure dislocations were observed in 19 cases, out of which according to the
      Robert's criteria, 13 children (68%) had excellent, three (15%) good, two (10%)
      fair, and one (7%)poor outcome. Out of the 29 elbow dislocations associated with
      other injuries, 3 (10%) had excellent, 4 (13%) good, 8 (27%) fair and 14 (50%)
      poor result. Reviewing the functional results, better range of motion was found
      in elbows with pure dislocation compared to those with associated injuries.
      Conclusion: Prolonged follow-up and effective rehabilitation programs are
      required for good outcomes.

PMID- 28435547
TI  - Transtubular Transoral Surgery for Excision of a Dystrophic Os Odontoideum: A
      Case Report.
AB  - Transoral approach to the cervico-medullary junction is a well-established
      procedure. However oropharyngeal complications in the form of soft tissue
      morbidity postoperatively do occur. We report a case of a teenage boy with
      traumatic quadriparesis secondary to compression of the cervico-medullary
      junction by an os odontoideum. Decompression was done via transoral approach
      through a tubular retractor system, hence obviating the need for the splitting or
      separate retraction of the soft palate and minimised the damage and violation of
      surrounding soft tissues. His neurological status improved and he was able to
      ambulate with support on fourth post-operative day with no soft tissue morbidity
      in the oral cavity. To our knowledge this is the first case reported using this
      technique. We conclude that adoption of this method would improve the traditional
      transoral approach and reduce the oropharyngeal complications.

PMID- 28435548
TI  - Thumb Schwannoma : A Frequent Misdiagnosis.
AB  - A 32 year-old Malay lady presented with a swelling over the dorsal surface of her
      right thumb for 6 months. The swelling was non-tender, smooth surfaced, mobile
      and nonfluctuating with no bony involvement. The provisional diagnosis was
      ganglion cyst. Excisional biopsy did not show features of ganglion cyst as it
      appeared to be wellencapsulated, multi-lobulated and yellowish in colour.
      Histopathological examination showed that it was a schwannoma. Schwannomas are
      relatively rare benign tumours which are frequently misdiagnosed. In this case,
      it was misdiagnosed both as a ganglion and a lipoma.

PMID- 28435549
TI  - Giant Cell Reparative Granuloma Mimicking Aneurysmal Bone Cyst in Proximal
      Phalanx of Toe.
AB  - Giant Cell Reparative Granuloma (GCRG) of phalanx is uncommon. It is a benign
      osteolytic lesion but can be locally aggressive. GCRG has certain radiology and
      histological features that are similar to other giant cell lesions of the bone.
      We present a case report of a young patient with giant cell reparative granuloma
      of proximal phalanx of left third toe. The bone lesion was successfully treated
      surgically.

PMID- 28435550
TI  - Peri-Implant Fractures Distal to an Antegrade Femoral Nail: A Case Series.
AB  - Peri-implant fractures distal to an antegrade femoral nail are uncommon injuries,
      with no current consensus on the best treatment modality. We are presenting three
      cases of periimplant fractures distal to an antegrade femoral nail. All patients
      sustained an initial traumatic injury, which was managed with an antegrade
      femoral nail fixation. They subsequently suffer a second injury which causes
      periimplant fracture. Our first two patients were managed with removing the
      intramedullary nail followed by Less Invasive Stabilization System (LISS) plate
      fixation. In our third case, the intramedullary nail was left in-situ, and the
      fracture was fixed with a polyaxial locking plate We discuss their injury
      pattern, investigations and surgical management. Polyaxial locking plates show
      great promise in this setting as they allow fixation of the fracture whilst
      maintaining the existing nail to protect the entire femur from further injury.

PMID- 28435551
TI  - Spinal Fusion for Chronic Low Back Pain: A 'Magic Bullet' or Wishful Thinking?
AB  - Chronic low back pain is a common, disabling and costly health problem. The
      treatment of chronic low back is difficult and is often ineffective. For
      treatment to be effective the cause of the pain has to be established but
      unfortunately in 80% to 95% of the patients the cause cannot be determined
      despite the existence of modern imaging techniques. A pathoanatomical diagnosis
      which fits into a classical disease model where successful treatment can be
      carried out, can only be made in 5% to 7% of the patients. The back pain in the
      rest of the patients where no pathoanatomical diagnosis can be made is often
      labelled, unscientifically, as chronic low back pain. Despite the existence of
      sophisticated imaging techniques and a plethora of diagnostic test the source of
      pain in patients with nonspecific back pain cannot be established. There exist no
      causal relationship between imaging findings of degenerated disc, lumbar facet
      arthritis, spondylosis, spondylolysis and spondylolisthesis, to the pain in these
      patients. Surgical treatment of non-specific back pain where no pathoanatomical
      diagnosis has been established is bound to fail. Therefore the outcome of spinal
      fusion in these patients can be no better than nonsurgical treatment. Spinal
      fusion is a major surgery which can be associated with significant morbidity and
      occasionally with mortality. Yet there is rapid rise in the rates of spinal
      fusion. There is a growing tension between ethics and conflicts of interest for
      surgeons. The spine, unfortunately, has been labelled as a profit centre and
      there are allegations of conflicts of interest in the relationship of doctors
      with the multi-billion dollar spinal devices industry. The devices industry has a
      significant influence on not only research publications in peer review journals
      but also on decisions made by doctors which can have a detrimental effect on the
      welfare of the patient.

PMID- 28435552
TI  - A Simple Cable Method for Intraoperative Limb Alignment Assessment.

PMID- 28435553
TI  - Prevalence and Associated Factors of Musculoskeletal Disorders among Young
      Dentists in Indonesia.
AB  - Introduction: Musculoskeletal problems are often work related. Dentists have been
      reported to have a high prevalence of musculoskeletal problems. Dentists have to
      perform repetitive tasks, often in awkward and nonergonomic positions in their
      practice. Materials and Methods: This is a cross-sectional study. Five-hundred
      copies of Nordic Musculoskeletal Questionnaire were distributed to dentists who
      participated in a congress of a regional branch of the Indonesian Dentist
      Association. Data such as sex, length of practice, the presence of assistance,
      smoking, occupational stress, body mass index, hand dominance, and exercise were
      collected. Dentist who had practised for more than five years were excluded.
      Results: Two hundred and forty-one respondents fulfilled the research criteria.
      Musculoskeletal symptoms occurred in 63.5% respondents. Fatigue and pain were the
      most common manifestations of musculoskeletal symptoms among dentists (36.5 and
      24.9% respectively). Prolonged sitting was the most common aggravating factor
      (26.6%) while exercise successfully relieved symptoms in 35.3% of respondents.
      Neck, upper back and lower back were the most common sites involved with
      prevalence of 25.7, 22.4, and 20.7% respectively. Neck was also the most common
      site of the symptoms preventing normal work during the preceding 12 months
      (8.3%). Exercise and stress are associated with the presence of musculoskeletal
      symptoms (p=0.01 and p<0.01 respectively). Exercise is associated with fatigue
      (p<0.01) and click (p<0.01), stress is associated with pain (p=0.00), stiffness
      (p=0.00), fatigue (p<0.01), and discomfort (p<0.01). Conclusions: The prevalence
      of musculoskeletal disorders in young dentists is 63.5%. Neck is the most common
      affected region. Stress and exercise are the main associated factor for
      musculoskeletal problems in dentists.

PMID- 28435554
TI  - Influence of Soluble Fillers in Improving Porosity of Handmade Antibiotic
      Impregnated Polymethyl Methacrylate (PMMA) Beads: An in-vitro Study.
AB  - There have been many investigations on non-biodegradable materials acting as an
      antibiotic carrier for local drug delivery systems based on polymethyl
      methacrylate (PMMA) beads. However, the material is non-degradable and non-porous
      so that less than 5% of the encapsulated drug is released. In order to obtain
      better release of the antibiotics, greater porosity of the beads would be
      required. Adding fillers could increase the bead's porosity, thus improving the
      antibiotic release from the beads. The purpose of the study is to optimize
      release kinetics of gentamicin from handmade beads by adding fillers such as
      glycine and sodium chloride in different concentrations. Terms of percolation
      theory will qualitatively be applied in interpreting the final results. Model
      beads were made by blending the antibiotics (gentamicin) with powdered PMMA,
      prepared with the inclusion of glycine and different concentration of sodium
      chloride in 100% monomer. To determine the gentamicin release, beads were placed
      in phosphate buffered saline (PBS) and aliquots were taken at designated times to
      measure the gentamicin concentration. Addition of glycine yielded 16 % release of
      the total amount of gentamicin incorporated in 24 hours. Subsequent addition of
      sodium chloride resulted in an increased gentamicin release, with little or no
      difference in gentamicin release once 16 g or more sodium chloride was added
      (gentamicin release 100% of the amount incorporated). In conclusion, addition of
      glycine and sodium chloride resulted in an increased release of gentamicin;
      however, the combination without sodium chloride seemed to have an inhibitory
      effect on the gentamicin release.

PMID- 28435555
TI  - The Radial Bow following Square Nailing in Radius and Ulna Shaft Fractures in
      Adults and its Relation to Disability and Function.
AB  - One of the points made against nailing in radius and ulna shaft fractures has
      been the loss of radial bow and its impact on function. The aims of the study
      were to assess the change in magnitude and location of the radial bow in radius
      and ulna shaft fractures treated with intramedullary square nails and to assess
      the impact of this change on functional outcome, patient reported disability and
      the range of motion of the forearm. We measured the magnitude of radial bow and
      its location in the operated extremity and compared it to the uninjured side in
      32 adult patients treated with intramedullary square nailing for radius and ulna
      shaft fractures at our institute. The mean loss of magnitude of maximum radial
      bow was 2.18 mm which was statistically significant by both student-T test and
      Mann-Whitney U test with p value less than 0.01. The location of maximum radial
      bow shifted distally but was statistically insignificant. The magnitude of
      maximum radial bow had a negative correlation with DASH score that was
      statistically insignificant (R=- 0.22, p=0.21). It had a positive, statistically
      significant correlation to the extent of supination in the operated extremity (R
      = 0.66, p = 0.0004). A loss of up to 2mm of radial bow did not influence the
      functional outcome as assessed by criteria reported by Anderson et al. The
      magnitude of radial bow influenced the supination of the forearm but not the
      final disability as measured by DASH score. Intramedullary nailing did decrease
      the magnitude of radial bow but a reduction of up to 2mm did not influence the
      functional outcome.

PMID- 28435556
TI  - Anterior Knee Pain after Tibial Intra-medullary Nailing: Is it Predictable?
AB  - Introduction: Intramedullary nailing has been used frequently for the treatment
      of tibial diaphyseal fractures. Chronic anterior knee pain has been considered
      the most frequent post-operative complication of this technique. We investigated
      the relationship between anterior knee pain and position of nail tip in proximal
      tibia. Methods: 103 patients were selected among patients who underwent
      interlocking nailing in our institution. Patients with other factors that might
      cause anterior knee pain were excluded. In all patients intramedullary nailing
      was done using transpatellar approach. The patients were evaluated in two groups,
      42 patients had anterior knee pain (Grup A), whereas 61 patients did not have
      pain (Group B). The distance from nail tip from tibial plateau was measured on
      lateral radiographs. Nail prominence from anterior tibial cortex was also
      measured. Results: The two groups were similar with respect to gender and follow
      up period. Out of 42 patients who had knee pain 21 (50%) had nail tip within
      proximal third distance from plateau to tibial tuberosity. Twenty-four patients
      (42%) among knee pain group had nail prominence of more than 5mm from anterior
      tibial cortex followed by 12 patients (29%) within 5mm and 12 patients (29%) nail
      tip buried within the anterior cortex. Conclusion: A greater incidence of knee
      pain was found when nail was prominent more than 5mm and when it is in the
      proximal third distance from tibial plateau to tuberosity. Patients should be
      aware of high incidence of knee pain when the nail tip is placed in proximal
      third and prominence of more than 5mm.

PMID- 28435557
TI  - Internal Fixation of Transverse Patella Fractures Using Cannulated Cancellous
      Screws with Anterior Tension Band Wiring.
AB  - Aims: To evaluate the effectiveness and safety of anterior tension band wiring
      technique using two cannulated cancellous screws in patients with transverse
      (AO34-C1) or transverse with mildly comminuted (AO34-C2) patellar fractures.
      Materials and Methods: This is a prospective study of 25 patients with transverse
      fracture or transverse fracture with mildly comminuted patella fractures. All the
      patients were treated with open reduction and internal fixation using two
      parallel cannulated screws and 18G stainless steel wire as per the tension band
      principle. Results: There were eighteen males (72%) and seven females (28%). The
      age group ranged from 24 to 58 years, with mean age of 38 years. The most common
      mode of injury was fall (72%) followed by road traffic accident (20%) and violent
      quadriceps contraction (8%). Transverse fracture was present in 60% and
      transverse fracture with mild comminution in 40% of patients. Mean time to
      achieve union was 10.7 weeks (range 8-12 weeks). Mean ROM at three months was
      113.8 degree (90-130) and at final follow up this improved to 125.4 degrees
      (range 100-140). There was one case of knee stiffness and no case of implant
      failure was observed. Patients were evaluated using Bostman scoring, the mean
      score at three months being 26.04 which improved to 27.36 at the end of final
      follow up at one year. Conclusion: Cannulated cancellous screws with anterior
      tension band wiring is a safe, reliable and reproducible method in management of
      transverse patellar fractures, with less chances of implant failure and soft
      tissue irritation.

PMID- 28435558
TI  - Nonunion of Fractures of the Ulna and Radius Diaphyses: Clinical and Radiological
      Results of Surgical Treatment.
AB  - Aseptic nonunion of the radius and ulna is a major complication of forearm
      fractures, accounting for 2% to 10% of all forearm fractures. The aim of our
      study is to evaluate the functional and radiological results of surgical
      treatment of diaphyseal aseptic nonunion of the radius and ulna, with autologous
      bone grafting, decortication and internal plate fixation. A series of 21 patients
      (26 nonunions) was retrospectively reviewed, the average age was 35 years with a
      mean of 31,58 years (range 12-44 years). The fractures included isolated radius
      (n=6) and ulna (n=10), and both radius and ulna (n=5). The Grace and Eversmann
      score was used to evaluate our results. Fifteen had very good results, five good
      and one average. Consolidation of the two bones was attained in 6.2 months.
      Therefore, the functional prognosis of the upper limb imposes the need for an
      adequate treatment. This management strategy has enabled us to have satisfactory
      results. However, the best treatment of nonunion remains the preventive treatment
      with an optimal management and care of the forearm fractures.

PMID- 28435559
TI  - Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection
      versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV
      Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.
AB  - Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the
      treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the
      regeneration of articular cartilage. This study analyses the efficacy of HA and
      PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross
      sectional study with retrospective review of 64 patients (101 knees) which
      includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results:
      During the post six months International Knee Documentation Committee (IKDC)
      evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in
      HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to
      0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as
      an optional treatment modality in Grade III and IV knee osteoarthritis in terms
      of functional outcome and pain control for up to six months when arthroplasty is
      not an option.

PMID- 28435560
TI  - Humeral Supracondylar Fractures in Children: A Novel Technique of Lateral
      External Fixation and Kirschner Wiring.
AB  - Introduction: Supracondylar fracture of the humerus is the most common fracture
      around the elbow in children. Pinning with Kirschner wires (K-wires) after open
      or closed reduction is generally accepted as the primary treatment modality.
      However, it comes with the risk of persistent instability and if the K-wire is
      not inserted properly, it may cause displacement and varus deformity. We present
      our two-year experience with a new technique of lateral external fixation and K
      wiring of the humeral supracondylar fracture. Materials and Methods: A total of
      seven children with irreducible Gartland Type III supracondylar humeral fracture
      were treated with closed reduction and lateral external fixation and lateral
      Kirschner wiring. Patients with ipsilateral radial or ulnar fracture, open
      fracture and presence of neurovascular impairment pre-operatively were excluded.
      All the patients were followed up at one, three and six weeks and three and six
      months. The final outcomes were assessed based on Flynn's criteria. Results: All
      the patients achieved satisfactory outcomes in terms of cosmetic and functional
      aspects. All patients except one (85.5%) regained excellent and good cosmetic and
      functional status. One patient (14.3%) sustained pin site infection which
      resolved with oral antibiotic (Checketts- Otterburn grade 2). There was no
      neurological deficit involving the ulnar nerve and radial nerve. Conclusion: The
      introduction of lateral external fixation and lateral percutaneous pinning
      provide a promising alternative method for the treatment of humeral supracondylar
      fracture. This study demonstrates that it has satisfactory cosmetic and
      functional outcomes with no increased risk of complications compared to
      percutaneous pinning.

PMID- 28435562
TI  - Avulsion Fracture of Brachioradialis Muscle Origin: An Exceedingly Rare Entity: A
      Case Report.
AB  - Avulsion fracture of the brachioradialis origin at its proximal attachment on the
      lateral supracondylar ridge of the distal humerus is exceedingly rare, and only
      two cases have been reported in the literature so far. In this article, we
      present a 38 years old patient who sustained a closed avulsion fracture of the
      lateral supracondylar ridge of left humerus at the proximal attachment of
      brachioradialis following a fall backwards on outstretched hand after being
      struck by a lorry from behind while riding on a two-wheeler (motorcycle). He was
      managed with above elbow plaster for four weeks followed by elbow and wrist
      mobilization. At final followup, the patient had painless full range elbow motion
      with good elbow flexion strength. The unique mechanism by which this avulasion
      fracture occurred is explained on the basis of the mode of injury, position of
      the limb and structure and function of the brachioradialis muscle.

PMID- 28435561
TI  - Solitary Osteochondroma of the Tibial Tuberosity Mimicking Osgood-Schlatter
      Lesion: A Rare Cause of Anterior Knee Pain in Adolescents: A Case Report.
AB  - Osteochondroma arising from the tibial tuberosity is very rare. We report such a
      case which mimicked OsgoodSchlatter's disease in an adolescent. A 12 years-old
      boy presented with swelling over his right proximal tibia of one year duration
      associated with pain in the last three months. Examination revealed a 4 x 2cm
      bony mass arising from the proximal tibia. Radiographs revealed an osteochondroma
      of the tibial tuberosity. Computer tomography and magnetic resonance imaging
      confirmed the continuity of the medulla of the bony mass to that of the parent
      bone. Excision biopsy was done. At the final follow up, he was asymptomatic and
      returned back to his daily activities. We present this case for its rarity,
      challenges involved in diagnosis and the difficulties encountered in planning the
      surgery because of involvement of the apophysis and extensor mechanism attachment
      in a skeletally immature boy.

PMID- 28435563
TI  - Ultrasound-guided Percutaneous Lavage in the Treatment of Calcific Tendinopathy
      of Elbow Extensor Tendons: A Case Report.
AB  - We report the efficacy of the ultrasound-guided percutaneous treatment in the
      management of elbow extensor tendons calcific tendinopathy. The ultrasound-guided
      percutaneous treatment is broadly used with positive results in patients
      suffering from rotator cuff calcific tendinopathy. However, this interventional
      method has been reported only in one patient in the medical literature. A 34
      years-old female who complained pain, swelling and severe functional limitation
      of the right elbow was referred to our unit. Elbow radiographs and ultrasound
      examination showed a soft-fluid calcification above the origin of the extensor
      tendons. Ultrasound-guided percutaneous treatment was therefore performed. After
      one year, the patient reported no pain and regained complete range of elbow
      motion. This method, in well trained hands, is an alternative treatment in the
      management of the uncommon elbow calcific deposit.

PMID- 28435564
TI  - Acute Paraplegia in a Toddler: A Diagnostic Journey Compounding the Challenge in
      Management: A Case Report.
AB  - Spinal tuberculosis is not common in the paediatric age group. Initial clinical
      features are often vague and non specific until the disease progresses to later
      stages. We highlight the diagnostic difficulties and management challenges of a
      complicated extradural tuberculoma with neurological deficits in a very young
      girl.

PMID- 28435565
TI  - Lumbosacral Plexopathy in Pelvic Injury - A Cause of Hip Instability in
      Acetabular Fractures: A Report of Two Cases.
AB  - Lumbosacral plexopathy is a rare clinical entity that results in potentially
      severe neurological deficit. The clinical presentation of lumbosacral plexopathy
      includes motor and sensory deficits. However to the best of our knowledge, hip
      instability secondary to lumbosacral plexopathy has not been reported in current
      literature. We report two cases of pelvic injury in which recurrent hip
      subluxation occurred following fixation of acetabular fractures. We attribute
      this to inadequate hip muscle tension from the associated lumbosacral plexopathy.
      In patients with acetabular fractures, this may lead to debilitating hip joint
      instability. In an already traumatized hip joint, this instability has a poor
      prognosis and can lead to degenerative changes with the eventual need for hip
      replacement.

PMID- 28435566
TI  - Functional Outcome of Bipolar Prosthesis versus Total Hip Replacement in the
      Treatment of Femoral Neck Fracture in Elderly Patients.
AB  - INTRODUCTION: The present study was performed to compare cemented total hip
      replacement (THR) with cemented bipolar prosthesis in the treatment of displaced
      fracture neck of femur in elderly patients. MATERIALS AND METHODS: This
      prospective study included 47 patients of greater than 60 years of age and having
      fracture of neck of femur, out of which 25 patients were managed by cemented
      bipolar prosthesis and remaining 22 were managed by cemented THR between June
      2011 and June 2013. These patients were followed up post-operatively for two
      years, at 6, 12 and 24 months, for functional analysis using Modified Harris Hip
      Score. RESULTS: Modified Harris Hip Score was significantly higher in the THR
      group as compared to the bipolar prosthesis group at 6, 12 and 24 months post
      operatively. Pain was almost similar in both the groups at all follow-up periods.
      Gait and range of motion was significantly higher in THR group as compared to
      bipolar prosthesis group at all-time point intervals. CONCLUSION: Cemented THR is
      a better option as compared to cemented bipolar prosthesis based on our short
      term functional outcome for the management of fracture of neck of femur in
      elderly patients.

PMID- 28435567
TI  - Role of Antibiotic Cement Coated Nailing in Infected Nonunion of Tibia.
AB  - INTRODUCTION: Infected nonunion of long bones is a chronic and debilitating
      disorder. It is more difficult to deal with when the implant used for internal
      fixation itself becomes a potential media for infection because of bacterial
      adhesion and biofilm formation. Traditionally, it is managed by two-stage
      procedure for controlling the infection first and then treating the nonunion.
      This study has been undertaken to explore antibiotic cement coated nailing as
      single stage treatment modality for treating infection and achieving stability at
      the same time. MATERIALS AND METHODS: Twenty patients (above 18 years of age)
      with infected nonunion of tibia with bone gap less than 2 cm were managed using
      antibiotic cement coated K-nail. Antibiotic cement nail was prepared using
      endotracheal tube method. Antibiotics used were a combination of vancomycin and
      teicoplanin. RESULTS: Infection was controlled in 95% of the patients. Bony union
      was achieved in 12 of 20 (60%) patients with antibiotic cement nailing as the
      only procedure with average time of union of 32 weeks. Remaining 8 patients
      required additional procedures like bone grafting or exchange nailing and these
      were done in six patients, with union of fracture. Two patients refused to
      undergo further procedures. Complications encountered were difficult nail removal
      in three cases, broken nail in two cases, and bent nail in one case. Recurrence
      of infection was observed in two patients. Average period of follow-up was 13
      months. CONCLUSION: Antibiotic cement impregnated nailing is a simple, economical
      and effective single stage procedure for the management of infected nonunion of
      tibia. It is advantageous over external fixators, as it eliminates the
      complications of external fixators and has good patient compliance. The method
      utilizes existing easily available instrumentation and materials and is
      technically less demanding, and therefore can be performed at any general
      orthopaedic center.

PMID- 28435568
TI  - Early Vessels Exploration of Pink Pulseless Hand in Gartland III Supracondylar
      Fracture Humerus in Children: Facts and Controversies.
AB  - The management of pink pulseless limbs in supracondylar fractures has remained
      controversial, especially with regards to the indication for exploration in a
      clinically well-perfused hand. We reviewed a series of seven patients who
      underwent surgical exploration of the brachial artery following supracondylar
      fracture. All patients had a non-palpable radial artery, which was confirmed by
      Doppler ultrasound. CT angiography revealed complete blockage of the artery with
      good collateral and distal run-off. Two patients were more complicated with
      peripheral nerve injuries, one median nerve and one ulnar nerve. Only one patient
      had persistent arterial constriction which required reverse saphenous graft. The
      brachial arteries were found to be compressed by fracture fragments, but were in
      continuity. The vessels were patent after the release of obstruction and the
      stabilization of the fracture. There was no transection of major nerves. The
      radial pulse was persistently present after 12 weeks, and the nerve activity
      returned to full function.

PMID- 28435569
TI  - Complications of Open Tibial Fracture Management: Risk Factors and Treatment.
AB  - Open tibial fractures result in high rates of complications. This study aims to
      elucidate the risk factors causing these complications, and suggest antimicrobial
      regimens based on the organisms grown in post-operative infections. Over a period
      of five years, 173 patients had sustained open tibial fractures and undergone
      operative treatment at a single institution. All surgical data was gathered
      retrospectively through online medical records. Thirty-one patients (17.9%) had
      sustained post-operative bony complications, while infective complications were
      reported in 37 patients (21.4%). Patients with Gustilo type III fractures were
      found to be more than three times as likely to sustain post-operative infective
      (p=0.007) or bony (p=0.015) complications, compared to Gustilo type I or II
      fractures. The fracture location and time taken to fixation did not significantly
      affect the complication rate, but results were trending towards significance. The
      commonest cause of infective complications were hospital-acquired organisms, such
      as Methicillin-resistant staphylococcus aureus (40.5%). Closer monitoring of
      patients sustaining high grade Gustilo open fractures, as well as antimicrobial
      prophylaxis for both hospital-acquired organisms and environmental contaminants,
      will result in the best outcome for patients. Further studies with larger sample
      sizes are warranted, to determine the significance of fracture location and time
      taken to fixation on complication rates.

PMID- 28435570
TI  - Outcome of Treatment of Osteoarthritis with Arthroscopic Debridement and
      Autologous Conditioned Plasma.
AB  - INTRODUCTION: Worldwide estimates are that 9.6% of men and 18.0% of women aged
      over 60 years have symptomatic osteoarthritis. The current treatment options vary
      from conservative to joint replacement. Recently, debridement of the joint has
      become an option for symptomatic relief. We evaluated the outcome of arthroscopic
      debridement with autologous conditioned plasma. The latter helps to promote
      cellular repair. We have evaluated our results over a two year period. MATERIALS
      AND METHODS: We retrospectively analyzed a cohort of 52 patients who underwent
      arthroscopic knee debridement with autologous conditioned plasma in 2011. The
      patients were followed up in clinic till discharge. The case notes were reviewed
      and baseline demographic data obtained. This included age, medical history,
      occupation, range of movement, BMI measurements, duration of operation and
      radiographic scores. We analyzed the outcomes against those factors. RESULTS: Of
      the 52 patients in our study, 16 were female and 36 were male. The mean follow-up
      period in the clinic was 6.5 months. The Kellgren-Lawrence score was 21.2% Grade
      1, 13.5% Grade 2, 51.9% Grade 3 and 13.5% Grade 4. Improvement in range of
      movement was seen in 32.7% of patients. CONCLUSIONS: This study shows that
      arthroscopic debridement with autologous conditioned plasma (ACP) has a role to
      play in the treatment of osteoarthritis. In view of these findings, we recommend
      that surgeons should consider arthroscopic debridement with autologous
      conditioned plasma as part of their treatment armamentarium.

PMID- 28435571
TI  - Outcome of Skeletal Reconstructive Surgery for Metastatic Bone Tumours in the
      Femur.
AB  - INTRODUCTION: The role of surgery in skeletal metastasis is to reduce morbidity
      and improve the quality of life in terminally ill patients. We report our
      experience with patients who underwent skeletal reconstructive surgery for
      metastatic bone tumour of the femur. MATERIALS AND METHODS: Twenty nine
      operations for skeletal metastasis of the femur performed in our centre between
      2009 and 2015 were included in this study. We evaluated the choice of implant,
      complications, survival rate and functional outcome. Fourteen patients were still
      alive at the time of this report for assessment of functional outcome using
      Musculoskeletal Tumour Society (MSTS) form. RESULTS: Plating osteosynthesis with
      augmented-bone cement was the most common surgical procedure (17 patients)
      performed followed by arthroplasty (10 patients) and intramedullary nailing (2
      patients) There were a total of five complications which were implant failures (2
      patients), surgical site infection (2 patients), and site infection mortality (1
      patient). The median survival rate was eight months. For the functional outcome,
      the mean MSTS score was 66%. CONCLUSION: Patients with skeletal metastasis may
      have prolonged survival and should undergo skeletal reconstruction to reduce
      morbidity and improve quality of life. The surgical construct should be stable
      and outlast the patient to avoid further surgery.

PMID- 28435572
TI  - Does Excision of Heterotopic Ossification of the Elbow Result in Satisfactory
      Patient-Rated Outcomes?
AB  - INTRODUCTION: Treatment of heterotopic ossification (HO) of the elbow is
      challenging and fraught with complications. Patients who sustain direct trauma to
      the elbow joint, the central nervous system, and thermal burns are at increased
      risk for development of HO. There is a paucity of studies and reports on
      patient's self-evaluation after the excision of the heterotopic ossification.
      MATERIALS AND METHODS: This retrospective study assessed outcomes after excision
      of heterotopic ossification around the elbow in a cohort of ten patients operated
      from 2012 to 2015. The outcome assessment was done by the Mayo Elbow Performance
      index (MEPI) and the American Shoulder and Elbow Surgeons-Elbow score (ASES-E
      scores). RESULTS: The mean follow-up was 18.11 months after the operation. The
      Mayo Elbow Performance Score was excellent in two elbows, good in six and fair in
      two. The mean gain in flexion-extension arc after excision of HO was 80 degrees.
      All of the patients had residual flexion deformity postoperatively. Eight of the
      nine patients were able to do activities requiring flexion at final follow-up.
      CONCLUSION: Excision of HO around the elbow is associated with satisfactory
      patient-rated outcomes in spite of failure to regain full range of motion.

PMID- 28435573
TI  - The Clinical Effectiveness of School Screening Programme for Idiopathic Scoliosis
      in Malaysia.
AB  - INTRODUCTION: There is no large population size study on school screening for
      scoliosis in Malaysia. This study is aimed to determine the prevalence rate and
      positive predictive value (PPV) of screening programme for adolescent idiopathic
      scoliosis. MATERIALS AND METHODS: A total of 8966 voluntary school students aged
      13-15 years old were recruited for scoliosis screening. Screening was done by
      measuring the angle of trunk rotation (ATR) on forward bending test (FBT) using a
      scoliometer. ATR of 5 degrees or more was considered positive. Positively
      screened students had standard radiographs done for measurement of the Cobb
      angle. Cobb angle of >10 degrees  was used to diagnose scoliosis. The percentage
      of radiological assessment referral, prevalence rate and PPV of scoliosis were
      then calculated. RESULTS: Percentage of radiological assessment referral (ATR >5
      degrees ) was 4.2% (182/4381) for male and 5.0% (228/4585) for female. Only 38.0%
      of those with ATR >5 degrees  presented for further radiological assessment. The
      adjusted prevalence rate was 2.55% for Cobb angle >10 degrees , 0.59% for >20
      degrees  and 0.12% for >40 degrees . The PPV is 55.8% for Cobb angle >10 degrees
      , 12.8% for >20 degrees  and 2.6% for > 40 degrees . CONCLUSIONS: This is the
      largest study of school scoliosis screening in Malaysia. The prevalence rate of
      scoliosis was 2.55%. The positive predictive value was 55.8%, which is adequate
      to suggest that the school scoliosis screening programme did play a role in early
      detection of scoliosis. However, a cost effectiveness analysis will be needed to
      firmly determine its efficacy.

PMID- 28435574
TI  - Subungual Glomus Tumours: Is Magnetic Resonance Imaging or Ultrasound Necessary
      for Diagnosis?
AB  - INTRODUCTION: Diagnosis of subungual glomus tumour is mostly based on detailed
      history and clinical examination. Recently, Magnetic Resonance Imaging (MRI) and
      Ultrasound have been proposed as the imaging modality to confirm the clinical
      diagnosis and in planning the surgical management of these tumours. However,
      these imaging modalities are not routinely available in rural setting and also
      are expensive. Due to these limitations, we set out to establish that diagnosis
      and management of these rare tumours can be based solely on a battery of clinical
      tests and history taking. MATERIALS AND METHODS: Retrospectively, we reviewed
      nine cases of glomus tumour. A clinical evaluation proforma was developed on the
      basis of clinical history and specific clinical test for diagnosis of these
      tumours. All the cases were evaluated and treated surgically by a single surgeon
      with a specific technique. Post-operatively, diagnosis was confirmed by
      histopathological examination. RESULTS: Females (77.78%) were predominantly
      affected in this series and the tumours commonly occurred in the right hand
      (66.66%). Spontaneous pain, cold sensitivity test and Love's Pin test was
      positive in all cases (100%). Hildreth's test was positive in 88.89%. In none of
      the cases the tumours recurred during minimum follow-up of one year. In all
      cases, histopathological examination confirmed the preoperative diagnosis of
      glomus tumours. CONCLUSION: Diagnosis of glomus tumours can be made clinically
      based on history taking and clinical examination. Magnetic Resonance Imaging and
      Ultrasound are not necessary for diagnosis and management of typical subungual
      tumours.

PMID- 28435576
TI  - A New Technique for Solving Tightrope Cutout during Acromioclavicular Joint
      Fixation: A Case Report.
AB  - Acromioclavicular joint (ACJ) dissociation is one of the common injuries
      affecting adults. The stability of ACJ largely depends on the integrity of
      acromioclavicular ligament, coracoclavicular ligament, capsule, trapezius muscle
      and deltoid muscle. The injury has been classified by Rockwood into six types and
      treatment options can be guided by the classification. TightRope fixation is one
      of the many surgical procedures available to address acromioclavicular joint
      separation. It consists of tensioning of a no. 5 Fibrewire suture secured at both
      ends to low-profile metallic buttons. Despite various advantages of using this
      technique, complications such as suture cut-out, clavicle fracture and suture
      failure have been documented. The author presents a case of a type III
      acromioclavicular joint dissociation treated with TightRope which suture cutout
      was noted intra-operatively. Decision to amend the fixation using a cut one-third
      tubular plate as an additional anchor for the metallic button on the clavicle was
      made. Patient's progress was evaluated using the University of California at Los
      Angeles Shoulder Score (UCLA Shoulder Score) and significant improvement was
      noted six months post operatively. We propose this technique as a solution to the
      encountered problem.

PMID- 28435575
TI  - Outpatient Percutaneous Release of Trigger Finger: A Cost Effective and Safe
      Procedure.
AB  - INTRODUCTION: Trigger finger is a common cause of pain and disability of the
      hand. Percutaneous release results in earlier functional recovery and patient
      satisfaction. This is a rapid and cost-effective method which saves a surgical
      procedure and results in better functional outcome. MATERIALS AND METHODS: This
      is a prospective observational study conducted on fifty-two fingers and thumbs in
      52 patients treated from 1st July 2014 till 31st December 2014, in the
      Orthopaedic Section, Department of Surgery, Aga Khan University Hospital,
      Karachi, Pakistan. All the baseline characteristics of the patients, like
      demographics, symptoms, Quinell's criteria and functional outcome were recorded.
      The patients were treated at our hospital with trigger finger, managed with
      percutaneous release using an 18 gauge needle and followed up for a minimum
      period of three months. The follow-up information included range of motion
      scoring, patient satisfaction and overall outcome of the procedure in terms of
      patient acceptance. The data was analyzed to determine the functional outcome at
      three months. RESULTS: There was complete release of A1 pulleys in 52 out of 52
      digits (100%) in the patients undergoing percutaneous release and significant
      patient satisfaction. No recurrence was observed. CONCLUSION: Percutaneous
      release of trigger finger with needle was not only associated with excellent
      functional outcome and recovery in terms of patient satisfaction and range of
      finger motion three months post-procedure but also was found to be cost
      effective.

PMID- 28435577
TI  - Intra-articular Localized Haemangioma of the Knee Mimicking Localized Pigmented
      Villonodular Synovitis: A Case Report.
AB  - Intra-articular synovial haemangioma of the knee is a benign tumour. However,
      diagnostic delay leads to degenerative changes in the cartilage and
      osteoarthritis due to recurrent haemarthrosis. Therefore, treatment should be
      performed immediately. We report the case of a localized synovial haemangioma
      arising from the medial plica in a 38-year old female presenting with pain and
      restricted range of motion in the right knee joint. Initially, we diagnosed this
      case as a localized pigmented villonodular synovitis (LPVS) based on MRI and
      arthroscopic findings and performed only arthroscopic en bloc excision of the
      mass and synovectomy around the mass for diagnostic confirmation. Fortunately,
      there was no difference in the treatment approaches for LPVS and localized
      haemangioma and the synovial haemangioma had not recurred at the 3-month
      postoperative follow-up with MRI. The patient's clinical symptoms resolved and
      had not relapsed two years after surgery.

PMID- 28435578
TI  - Use of an Industrial Tungsten Carbide Drill in the Treatment of a Complex
      Fracture in a Patient with Severe Osteopetrosis: A Case Report.
AB  - The treatment of fractures in osteopetrosis can be complicated and difficult. We
      describe the use of an industrial grade tungsten carbide drill bit in the
      treatment of one of these complex fractures. An industrial grade tungsten carbide
      drill bit was used to fashion a medullary canal in the surgical treatment of a
      left peri-implant fracture of the neck of femur in a patient with osteopetrosis.
      The patient was successfully treated with a hemiarthroplasty with good functional
      outcomes. A tungsten carbide drill bit serves as an effective and safe option in
      the treatment of osteopetrotic femoral neck fractures.

PMID- 28435579
TI  - Peripheral Gangrene Complicating Systemic Lupus Erythematosus in a Patient with
      Spina Bifida: A Case Report.
AB  - An adolescent girl, a known case of spina bifida with systemic lupus, presented
      with bluish discolouration of three toes of the right foot. She had thrombosis of
      bilateral popliteal arteries. She underwent percutaneous transluminal angioplasty
      (PTA) of both legs and Chopart amputation of the right foot. Systemic lupus
      erythematosus (SLE) occurring in a patient with spina bifida has not been
      previously reported. Weakness, sensory loss, lack of normal ambulation,
      endarteritis, antiphospholipid antibody syndrome are common contributory factors
      for peripheral gangrene in patients with spina bifida with systemic lupus
      erythematosus.

PMID- 28435580
TI  - First and Second Metatarsophalangeal Joint Open Dislocations: A Case Report.
AB  - Dislocation of multiple metatarsophalangeal joint is an uncommon injury. The
      mechanism of injury is a high energy force distal to proximal with foot in
      hyperextension at the metatarsophalangeal (MTP) joint. The acute hyperextension
      of the toe at the moment of injury causes avulsion of the plantar part of the
      capsule from the junction of head and neck of the metatarsal. If the collateral
      ligaments remain intact, they maintain the locked fibrocartilaginous plate over
      the dorsum of the head of the metatarsal, making closed reduction impossible. We
      report a case of simultaneous 1st and 2nd MTP joint open dislocation. In the
      present case, we chose the plantar approach utilizing the already present plantar
      wound. At 18 months post-operative follow-up, there was no instance of
      redislocations or signs of avascular necrosis of head of metatarsal.

PMID- 28435581
TI  - Bilateral Asymmetrical Fracture Dislocation of Shoulder with Rare Combination of
      Injuries after Epileptic Seizure: A Case Report.
AB  - The incidence of bilateral gleno-humeral joint dislocation is rare, is almost
      always posterior and is usually caused by sports injuries, epileptic seizures,
      electrical shock, or electroconvulsive therapy. Bilateral fracture-dislocation is
      even rarer, with a few cases reported in the literature. We report an unusual
      case with dislocation of the both glenohumeral joints in opposite direction after
      a seizure episode, with fracture of greater tuberosity on one side and of the
      lesser tuberosity on the contralateral side. Although there have been a few
      reports of bilateral asymmetric fracture dislocations of the shoulder in the
      past, an injury pattern resembling our case has, to the best of our knowledge,
      not been described in the literature so far. This report includes a detailed
      discussion regarding the mechanism of injury in a case of asymmetrical
      dislocation following a seizure episode. At final follow-up, the patient had
      healed fractures, painless near normal range of motion with no redislocations.

PMID- 28435582
TI  - Transient Osteoporosis of the Hip: A Case Report.
AB  - Transient osteoporosis of the hip (TOH) is a benign, selflimiting condition
      characterised by acute onset groin pain in adults. Early diagnosis is important
      to differentiate it from progressive conditions such as osteonecrosis. We report
      on a middle-aged male who presented with right groin pain without any prior
      trauma. The diagnosis of transient osteoporosis of hip was confirmed by Magnetic
      Resonance Imaging (MRI) and he was successfully treated with a course of
      Alendronate sodium, anti-inflammatory analgesics and a period of non-weight
      bearing ambulation.

PMID- 28435583
TI  - Ulnar Osteotomy with 2-Pin Unilateral Gradual Distraction for Treatment of
      Chronic Monteggia Fracture: A Case Report.
AB  - Missed Monteggia fracture leading to chronic radial head dislocation is a known
      complication. The surgical treatment options remain challenging. The aim of
      treatment is to reduce the radial head and to maintain the stability of the elbow
      in all ranges of motion. A few surgical techniques have been described with
      complications. We report the case of a 13 years old boy with chronic radial head
      dislocation as a result of an unrecognised Monteggia fracture-dislocation for
      eight years. We successfully reduced the radial head and corrected the cubital
      valgus from 45 degrees to 10 degrees with a proximal ulna osteotomy and gradual
      distraction with 2-pin Monotube external fixator. The correction was uneventful
      with good functional outcome.

PMID- 28435584
TI  - Intra-articular Entrapment of Medial Epicondyle Fracture Fragment in Elbow Joint
      Dislocation Causing Ulnar Neuropraxia: A Case Report.
AB  - Traumatic elbow dislocations in children are rare but most of them are complex
      dislocations, and in such dislocations, medial humerus epicondyle fractureis the
      most common associated injury. Fracture incarceration in the elbow joint occurs
      in 5-18% of medial humerus epicondyle fractures but ulnar neuropraxia is very
      rare. Open reduction internal fixation is indicated in medial humerus epicondyle
      fracture with fracture incarceration, ulnar neuropraxia, marked instability or
      open fracture. Operative treatment options include fragment excision and sutures,
      closed or open reduction and Kirschner wire fixation, open reduction and suture
      fixation, open reduction and smooth pin fixation, and open reduction and screw
      fixation. However, ulnar nerve transposition is debatable as good outcome had
      been reported with and without nerve transposition. We report a case of a 13-year
      old boy, who presented with right elbow dislocation and intra-articular
      entrapment of medial humerus epicondyle fracture fragment, complicated with
      sensory ulnar neuropraxia, following a fall onto his right outstretched hand in a
      motor vehicle accident. The elbow joint was reduced using close manipulative
      reduction but the fracture fragment remained entrapped post-reduction. The
      patient then underwent open reduction and screw fixation of the medial humerus
      epicondyle fracture without ulnar nerve transposition. He had good functional
      outcome six weeks after surgical intervention, with complete recovery of ulnar
      neuropraxia six months later. Currently, he is doing well at school and is active
      with his sporting activity.

PMID- 28435585
TI  - Perforators in the Leg: Why It Is Important for Orthopaedic Surgeons to Know.

PMID- 28435586
TI  - Haglund Deformity - Surgical Resection by the Lateral Approach.
AB  - The aim of this study was to analyse the outcome of surgical Haglund deformity is
      a prominence in the postero superolateral aspect of the calcaneum. Haglund
      deformity is a prominence in the postero superolateral aspect of the calcaneum,
      causing a painful bursitis, which may be difficult to treat by non-operative
      measures alone. Various surgical methods are available for effective treatment of
      refractory Haglund's deformity. This study is to evaluate whether adequate
      resection of Haglund deformity by a lateral approach provides good to excellent
      results. During the period from 2009 to 2012, 40 patients with 46 feet had
      undergone resection of Haglund deformity using lateral approach and the outcome
      was analysed using AOFAS Ankle-Hind Foot Scale. The mean AOFAS score at the
      follow up was 86/100, with the majority of patients reporting alleviation of pain
      at one year follow up. The lateral approach to calcaneal ostectomy can be an
      effective treatment for those suffering from refractory Haglund deformity.
      However, the patient must be made aware of theduration of recovery being long.

PMID- 28435587
TI  - The Morphometric Study of Degenerative Lateral Canal Stenosis at L4-L5 and L5-S1
      Using Magnetic Resonance Imaging (MRI): Feasibility Analysis for Posterior
      Surgical Decompression.
AB  - This study was to evaluate the morphological features of degenerative spinal
      stenosis and adequacy of lateral canal stenosis decompression via unilateral and
      bilateral laminectomy. Measurements of facet joint angulation (FJA), mid facet
      point (MFP), mid facet point distance (MFPD), the narrowest point of the lateral
      spinal canal (NPLC) and the narrowest point of the lateral spinal canal distance
      (NPLCD) were performed. At L4L5 of the right and left side, the mean distance
      between the lateral border of the dura and MFP was 1.0 +/- 0.2 cm and 1.0 +/-
      0.3cm respectively. The mean NPLC was seen at 0.7 +/- 0.3 and 0.7 +/- 0.3 cm cm
      from the dura. At L5S1 of the right and left side, the mean distance between the
      lateral border of the dura and MFP was 1.2+/- 0.2 and 1.3 +/- 0.2 cm
      respectively. The mean NPLC was seen at 0.8 +/- 0.4 and 0.9 +/- 0.5 cm from the
      dura. Unilateral laminectomy may result in incomplete decompression.

PMID- 28435588
TI  - A Four-year Review of Delayed Initial Treatment of Patients with Congenital
      Talipes equinovarus in a General Hospital.
AB  - Congenital Talipes Equinovarus (CTEV), or club foot, is a common congenital
      orthopaedic abnormality of the foot, which is easily diagnosed but difficult to
      treat perfectly. Controversy in terms of its etiology, classification and
      management continues to exist. Delayed initial treatment in patients with
      clubfoot has a strong correlation with a poor outcome. The purpose of this study
      was to review the factors that influence the outcome in patients who get delayed
      initial treatment at Hasan Sadikin General Hospital so that poor outcome can be
      prevented. We reviewed the medical records of 15 patients (23 feet) during the
      period from January 2009 to December 2013 and analysed various factors including
      gender, age at time of first treatment, type of disorder, the level of success of
      non-surgical therapy, parent education level, family income and accessibility to
      health care centre. CTEV was more common in girls in our patients who were in the
      6-12 months age group. The most common type of CTEV was the flexible type.
      Treatment with serial casting produced good results in most patients. The
      majority of parents' educational level was junior high school and had 2-5
      million/month income. The accessibility of patients to health care centre was
      difficult.

PMID- 28435589
TI  - Proximal Tibia Bone Graft: An alternative Donor Source especially for Foot and
      Ankle Procedures.
AB  - Bone graft is essential in various orthopaedic procedures. Among the many donor
      sites for harvesting autologous bone graft, the iliac crest has been the most
      commonly used. However, for foot and ankle procedures the proximal tibia has
      gained popularity as an alternative donor site due to its anatomic proximity to
      the primary surgical site. In this article we evaluated the possible
      complications associated with harvesting proximal tibia bone graft. Our study
      showed the low incidence of morbidity in harvesting proximal tibia bone graft,
      thereby providing a good alternative donor for foot and ankle procedures.

PMID- 28435590
TI  - Delayed Operative Management of Fractures of the Lateral Condyle of the Humerus
      in Children.
AB  - PURPOSE: Delayed presentation of lateral condylar fractures of the humerus is
      relatively common in the developing regions of the world. These fractures are
      difficult to manage because of the displacement and fibrosis around the condylar
      fragment secondary to the delay. There is a paucity of literature concerning the
      management of these fractures. An oft repeated finding is the requirement of
      extensive dissection around the fragment for proper reduction. The purpose of
      this study was to assess the efficacy of surgical management of lateral condylar
      fractures with delayed presentation. METHODS: We assessed the results of lateral
      condylar fracture fixation in 20 cases with delayed presentation. RESULTS: The
      lateral condylar fractures in patients with a delayed presentation can be managed
      surgically with good results. CONCLUSIONS: Open reduction and internal fixation
      should continue to be the method of choice for the management of lateral condylar
      fractures which report late for management.

PMID- 28435591
TI  - Variants of Monteggia Type Injury: Case Reports.
AB  - BACKGROUND: Monteggia fracture-dislocation is rare in children. Various reports
      attest to its rarity, while recording the many variant of this injury. It is,
      therefore, easy to miss the diagnosis in the absence of proper clinical
      examination and radiographs. CASE REPORT: This report highlights two rare
      variants of Monteggia fracture-dislocation seen in children. The first case was a
      12-year old girl alleged to have fallen from a 15- feet tall tree and sustaining
      a combined type III Monteggia injury with ipsilateral Type II Salter-Harris
      injury of distal end radius with a metaphyseal fracture of the distal third of
      the ulna. The second case was a 13-year old who had sustained a closed fracture
      of atypical Type I Monteggia hybrid lesion, in a road traffic accident.
      CONCLUSION: This report highlights the rare variants of Monteggia fracture
      dislocation which could have been missed without proper clinical examinations and
      radiographs.

PMID- 28435592
TI  - Ganglion of the Flexor Tendon Sheath at the A2 Pulley - Case Report.
AB  - There are few reported cases of flexor tendon sheath ganglion arising from the A2
      pulley. We report a case of a flexor tendon sheath ganglion in a 17-year old
      female who presented with pain, triggering and a swelling at the base of her
      right ring finger. During the excision biopsy, a ganglion measuring 0.5*0.8*0.4
      cm in size was removed from the A2 pulley area.

PMID- 28435593
TI  - Traumatic Anterior Dislocation of Hip in a Child - Case Report.
AB  - Traumatic hip dislocation in children is relatively rare accounting for about 5%
      of all hip dislocations. Most of the hip dislocations seen in children are of the
      posterior type but the much rarer anterior and anterior-inferior (obturator)
      types have also been described. We present the case of an eight years old girl
      with an obturator type of hip dislocation following trivial trauma. She was
      treated with closed reduction and immobilisation in skin traction for three
      weeks. She was followed up closely for one year and did not develop any
      complications during that period.

PMID- 28435594
TI  - Complete Recovery of Thoracic Myelopathy after Eleven Months of Paraplegia: A
      Case Report.
AB  - Instances of neurological recovery after early decompression of the spine in non
      traumatic spinal cord compression are well documented. We present a patient with
      paraplegia of 11 months' duration due to atypical spinal tuberculosis who showed
      complete neurological recovery in three months.

PMID- 28435595
TI  - Painful Lytic Lesions of the Foot: A Case Report.
AB  - The presence of lytic lesions in the bones of foot raises a number of diagnostic
      possibilities ranging from infection, inflammatory pathology to neoplastic
      conditions. Although the radiological picture is not pathognomonic of any
      pathology, clinical history and histopathological examination can help to clinch
      the diagnosis. We present a case of multiple lytic lesions of the foot and
      discuss possible differential diagnoses. The patient was diagnosed as a case of
      madura foot and the lesions responded to surgical debridement and anti-fungal
      treatment with a good functional outcome. Madura foot is an uncommon, chronic
      granulomatous fungal or bacterial infection with a predilection in people who
      walk barefoot. Although known for a specific geographical distribution, madura
      foot should be kept as a possible diagnosis in patients presenting with lytic
      lesions of the foot due to population emigration across the world.

PMID- 28435596
TI  - Phalangeal Osteosarcoma Mistaken for Tuberculosis: A Case Report.
AB  - We report a 21-year old female patient who presented with an 18-month history of
      a swelling in the distal phalanx of her right little finger. Although the
      history, clinical features and MRI were suggestive of a benign tumour or a
      tuberculous lesion, the histo-pathological examination of the swelling was
      reported as a conventional osteosarcoma. Osteosarcoma of the hand is very rare.
      This article highlights the possibility of a seemingly benign lesion seen in a
      routine clinic could well turn out to be malignant, and the need to maintain a
      high index of suspicion.

PMID- 28435597
TI  - Metacarpal Lengthening Of The Thumb Via Distraction Osteogenesis: A Case Report.
AB  - Amputation of the thumb invariably causes marked functional impairment of the
      hand especially, pinch and grasp functions. In rural areas where highly skilled
      microvascular surgeries are not available, distraction osteogenesis provides an
      easy and safe alternative of thumb reconstruction. We report a case of crush
      injury of the right hand in a 37 year old gentleman in which the right thumb was
      amputated at the level of the proximal phalanx. Metacarpal lengthening of the
      thumb was performed by using distraction osteogenesis.

PMID- 28435598
TI  - A Rare Case of Pseudotumor Formation following Total Knee Arthroplasty.
AB  - A 59 year old man who had undergone left total knee arthroplasty in 2008
      presented with a 5 month history of left knee pain and persistent swelling.
      Workup for infection was negative and the patient was suspected to be suffering
      from particle disease and chronic synovitis. Imaging revealed an internally
      rotated tibial component. Intraoperative findings revealed extensive polyethylene
      wear with resultant metalon- metal articulation, soft tissue metallosis and a
      pseudotumor like mass at the posterolateral aspect of the popliteal fossa. This
      was extensively debrided and revision knee arthroplasty was performed. Suboptimal
      component alignment can lead to localized high loading, wear and metallosis,
      which in this case resulted in the formation of a pseudotumor.

PMID- 28435599
TI  - "Doc' do I need an anterior cruciate ligament reconstruction? What happens if I
      do not reconstruct the cruciate ligament?"
AB  - We are all aware that there has been a dramatic increase in the number of
      anterior cruciate ligament (ACL) reconstructions that are carried out here in
      Malaysia as well as around the world. The numbers of ACL injuries have
      undoubtedly increased over the years with greater participation of young adults
      in sporting activities. However it is not certain whether the increase in the
      numbers of reconstructions can be accounted for by the increasing numbers of ACL
      injuries. Without doubt commercial interests as well the influence of the
      biomedical companies have a role to play. In the past the rational for surgical
      treatment of an ACL tear was that the ACL is vital for knee function and that in
      the long term ACL deficiency will lead to more injuries of the meniscus and more
      degeneration of the joint. This belief was prevalent because the natural history
      of an ACL deficient knee was not known although the ultimate outcome of
      reconstruction of the ACL was not known either. However in past few years a
      substantial amount research has been published, which has elucidated the natural
      history of ACL deficient knees as well as the long term outcome of reconstruction
      of the ACL.

PMID- 28435600
TI  - Plagiarism: The Bane of Publishing.

PMID- 28435601
TI  - Posterior Cruciate Ligament Tibial Avulsion treated with Open Reduction and
      Internal Fixation through the Burks and Schaffer Approach.
AB  - OBJECTIVE: To report functional outcome in Posterior Cruciate Ligament (PCL)
      tibial avulsion fractures treated with open reduction and internal fixation
      through Burks and Schaffer approach. The patient specific functional outcome
      measures like IKDC grading together with objective grading with stress
      radiographs have rarely been used -to assess PCL tibial avulsion fractures.
      MATERIAL AND METHODS: Twenty seven patients (21 males and 6 females) were
      included in the study. The mean follow up duration was 22.30+/-6.82 months. They
      were assessed using international knee documentation committee (IKDC) grades,
      Lysholm scoring and stress radiography. The injury severity scores (ISS) of the
      patients were also recorded. RESULTS: The mean Lysholm scores at the time of last
      follow up was 90.85+/-5.58. The IKDC grades achieved were normal in 20 patients,
      near normal in five and abnormal in two. The PCL laxity determined on active
      hamstring contraction stress radiography was grade I in 20 cases and grade II in
      seven cases. All patients had achieved bony union of tibial avulsion fractures at
      the time of last follow up. Statistically significant association was found
      between higher ISS and lower Lysholm scores. (t=3.455, p=0.0019). Good IKDC
      grades were associated with higher Lysholm scores (analysis of variance, F=32.51,
      p<.0001). There was no correlation between PCL laxity and functional outcome
      (t=.857, p = 0.399). CONCLUSION: PCL tibial avulsion fractures treated through
      Burk and Schaffer approach with open reduction and internal fixation produces
      good results. The early rehabilitation without cast immobilisation prevents
      arthrofibrosis.

PMID- 28435602
TI  - Clinical Measurement of the Tibio-femoral Angle in Malay Children.
AB  - BACKGROUND: This study was conducted to find out the age when tibiofemoral angle
      starts to be in valgus and reaches maximum angle. The differences of the angles
      between genders were also studied. METHODOLOGY: This cross sectional study on
      tibiofemoral angle was conducted among 160 normal healthy children using clinical
      measurement method. The children between 2 18 months to 6 years old were assigned
      to 5 specific age groups of 32 children with equal sex distribution. RESULT: This
      study had shown a good inter-observer reliability of tibiofemoral angle
      measurement with intraclass correlation coefficient (ICC) of 0.87 with narrow
      margin of 95% confident interval (95% CI: 0.73, 0.94). The mean tibiofemoral
      angle for children at 2 , 3 , 4 , 5 and 6 years old were 2.25 degrees  (SD=0.53),
      8.73 degrees  (SD=0.95), 7.53 degrees  (SD=1.40), 7.27 degrees  (SD=1.14) and
      6.72 degrees  (SD=0.98) respectively. The age when they achieved maximum valgus
      tibiofemoral angle was 3 years old. The maximum mean (SD) tibiofemoral angle for
      boys, girls and all children were 8.91 degrees  (SD=1.17), 8.56 degrees 
      (SD=0.62) and 8.73 degrees  (SD=0.95)respectively. The mean tibiofemoral angle
      showed no statistically significant difference between girls and boys except for
      the 5-year-old group, in which the mean TF angle for girls was 7.560 (SD=0.95)
      and for the boys was 6.970 (SD=1.26) with p-value of 0.037. CONCLUSION:
      Measurement of tibiofemoral angle using the clinical method had a very good inter
      observer reliability. The tibiofemoral angle in Malay population was valgus since
      the age of 2 years with maximum angle of 8.730 (SD=0.95) achieved at the age of 3
      years.

PMID- 28435603
TI  - The Rubber Stopper: A Simple and Inexpensive Technique to Prevent Pin Tract
      Infection following Kirschner Wiring of Supracondylar Fractures of Humerus in
      Children.
AB  - Percutaneous pinning after closed reduction is commonly used to treat
      supracondylar fractures of the humerus in children. Minor pin tract infections
      frequently occur. The aim of this study was to prevent pin tract infections using
      a rubber stopper to reduce irritation of the skin against the Kirschner (K) wire
      following percutaneous pinning. Between July 2011 and June 2012, seventeen
      children with closed supracondylar fracture of the humerus of Gartland types 2
      and 3 were treated with this technique. All patients were treated with closed
      reduction and percutaneous pinning and followed up prospectively. Only one
      patient, who was a hyperactive child, developed pin tract infection due to
      softening of the plaster slab. We found using the rubber stopper to be a simple
      and inexpensive method to reduce pin tract infections following percutaneous
      pinning.

PMID- 28435604
TI  - Meniscal Extrusion in the Knee: Should only 3 mm Extrusion be Considered
      Significant? An Assessment by MRI and Arthroscopy.
AB  - AIM: The aim of this study was to assess whether significant meniscal extrusion
      of more than 3 mm or of even lesser degrees of extrusion could be considered
      significant. We also aimed to determine the morphology of tears that are most
      likely to be associated with significant extrusion. Study design and material.
      The study was done retrospectively on a group of 202 patients (157 males and 45
      females) who had been seen in our hospital between 2007 and 2011 with meniscal
      tears (in one knee only) diagnosed by MRI and confirmed on arthroscopy. Extrusion
      of 3 mm or more (usually considered significant) was seen in 102 cases and less
      than 3 mm in 100. Extrusion was measured on the coronal MR images rather than on
      saggital images because of ease and reproducibility. The tears were confirmed by
      arthroscopy and correlated with the extent of extrusion on MRI. RESULTS: Out of
      the total of 202 cases, 102 cases (50.5%) had extrusion of 3 mm or more on MRI.
      Of these, the medial meniscal posterior horn tears accounted for 63 cases
      (64.26%), 21 cases were medial meniscal body tears (21.42%), five medial meniscal
      root tears (5.1%), nine lateral meniscal body tears (9.18%) and four lateral
      meniscal posterior horn tears(4.08%). Forty-four cases had extrusion of 3-4 mm,
      26 had extrusion of 4-5mm, 17 cases had extrusion of 5-6mm, ten had extrusion of
      6-7mm and five had extrusion of 7 mm or more. One hundred cases fell in the < 3mm
      extrusion category, of which 80 (39.6%) were in the 2-3 mm extrusion group and 20
      (9.9%) in the 1-2 mm extrusion group. They comprised of 61 cases of medial
      meniscal posterior horn tears, 23 cases of medial meniscal body tears, six medial
      meniscal root tears, eight lateral meniscal body tears and two lateral meniscal
      posterior horn tears. The highest proportion of meniscal tears was seen in the 2
      3 mm category comprising nearly 40% of the entire study group. The majority of
      tears were medial meniscal posterior horn tears. CONCLUSION: Menisci that
      extruded 2-3 mm from the tibial margin formed a major proportion of menisci
      treated for tears by repair or menisectomy. We should consider extrusion of more
      than 2mm as significant. Most tears had extrusion of 2-4 mm.

PMID- 28435605
TI  - Prevalence of Vitamin D Deficiency in Patients Presenting with an Orthopaedic
      Trauma at a Tertiary Centre in South India - Implications and Protocols for
      Replacement Therapy.

PMID- 28435606
TI  - Posterior Cruciate Ligament Tibial Avulsion treated with Open Reduction and
      Internal Fixation.
AB  - The optimal treatment for thoracolumbar fractures (TLF) without neurological
      deficit remains controversial. Majority of the systematic reviews and meta
      analyses have evaluated open operative approaches but have yet to compare the
      outcomes of minimally invasive percutaneous pedicle fixation (MIPPF) versus non
      operative treatment. A retrospective cohort study was performed to compare
      clinical and radiological outcomes between MIPPF and conservative groups for TLF
      AO Type A1 to Type B2 during a 2-year follow-up period. Pre-operative plain and
      CT films were evaluated and decision made for short segment (non-fusion) MIPPF.
      Patients who refused operation were treated conservatively with three months of
      body cast, brace, or corset. MIPPF group showed earlier Visual Analog Score(VAS)
      improvement at six months post-injury (0 vs 6.0- p<0.001), as well as better
      functional and radiological outcomes (p<0.050) at final follow-up. Progressions
      of regional kyphosis (RK) were noted in both groups but there was no significant
      difference within and between them(p>0.050). MIPPF as a method of internal
      bracing can be pursued in the treatment of TLF, with larger future cohorts and
      RCTs being called for to support and explore new findings.

PMID- 28435607
TI  - Femoral Neck Anteversion and Neck Shaft Angles: Determination and their Clinical
      Implications in Fetuses of Different Gestational Ages.
AB  - Precise anatomical assessment of femoral neck anteversion (FNA) and the neck
      shaft angles (NSA) would be essential in diagnosing the pathological conditions
      involving hip joint and its ligaments. The present study was undertaken on 48
      fetal femurs to calculate the NSA and FNA in fetuses digitally. End on images of
      upper end of the femurs were taken for the estimation of FNA and a photograph in
      a perpendicular plane was taken to calculate the NSA. Microsoft Paint software
      was used to mark the points and Image J software was used to calculate the angles
      digitally. The FNA ranged from 17.08o to 33.97 o on right and 17.32 o to 45.08 o
      on left. The NSA ranged from 139.33 o to 124.91 o on right and 143.98 o to 123.8
      o on left. Unpaired t test showed the FNA and NSA of femur did not vary
      significantly during the third trimester.

PMID- 28435608
TI  - Does the Quality of Life in Operated Patients with Adolescent Idiopathic
      Scoliosis correspond with the Radiographic Parameters?
AB  - OBJECTIVES: Traditionally, scoliosis surgery is aimed at attaining a fused,
      balanced and painless spine. With improvement in surgical and instrumentation
      techniques, spine surgeons strive to achieve higher degree of Cobb's angle and
      rib hump correction with the idea of greater patient satisfaction. The aim of
      this study was to determine the patients' satisfaction using SRS-22 questionnaire
      and their correlations with the radiographic changes. MATERIALS AND METHODS: A
      prospective study was conducted in a tertiary referral cen re using the Scoliosis
      Research Society-22 (SRS-22) questionnaire during the patients' annual follow up,
      betwee February to April 2014. Thirtyseven patients who met the inclusion
      criteria were enrolled. RESULTS: The mean pre-operative Cobb's angles were 57.8o
      +/- 12.7o and mean post-operative angle of 20.0o +/- 10.4o, resulting in average
      correction of 65.9 +/- 14.4%. Mean preoperative rib hump was 61.1 +/- 15.4 mm
      with mean postoperative rib hump of 15.8 +/- 17.8 mm, resulting in average
      reduction of 77.7 +/- 23.7%. Mean of post-operative total SRS score was 4.1 +/-
      0.5. Using Spearman rank correlation, the percentage of Cobb's angle correction
      versus the SRS-22 score showed correlation of 0.17 (P=0.33) while the percentage
      of rib hump reduction versus SRS-22 score showed a correlation of 0.11 (P=0.53).
      CONCLUSION: In this study, the average total SRS-22 score was 4.1 +/- 0.5 (range,
      3.1-4.9) post-operatively indicating very high satisfaction rate overall. Despite
      attempts at greater curve correction and rib hump reduction, there is no direct
      correlation between patient satisfaction and radiographic parameters.

PMID- 28435609
TI  - Splinting after Carpal Tunnel Release: Does it really Matter?
AB  - : Splinting of the wrist after carpal tunnel release (CTR) has been practised by
      many surgeons especially in North America. The main reason was to prevent
      possible adverse events of bowstringing of flexor tendons and the median nerve,
      pillar pain, entrapment of the median nerve in scar tissue and wound dehiscence.
      Studies on the effect of splinting after standard CTR have had dismal results.
      The duration of splinting in standard CTR has been either too long (for 2-4
      weeks) or too short (48 hours only). The aim of our study was to compare the
      effects of post-operative splinting for a duration of one week with no splinting.
      METHODS: All 30 of our patients underwent a standardized limited open CTR by a
      designated surgeon. Post operatively, they were randomized into a splinted (n=16)
      and a nonsplinted (n=14) group. The splint was kept for a week. Patients were
      reviewed at regular intervals of one week, two months and six months. At each
      follow up, these patients were clinically assessed for the following outcome
      measures: VAS (visual analogue score), 2PD (two-point discrimination), pinch
      grip, grip, Abductor Pollicis Brevis (APB)) power and completion of the Boston
      questionnaire. RESULTS: All patients presented with significant improvement in
      the postoperative evaluation in the analyzed parameters within each group.
      However, there was no significant difference between the two groups for any of
      the outcome measurements at sequential and at final follow-up. CONCLUSION: We
      conclude that wrist splinting in the immediate post-operative period has no
      advantage when compared with the unsplinted wrist after a limited open carpal
      tunnel release.

PMID- 28435610
TI  - Adolescent Volar Barton Fracture with Open Physis treated with Volar Plating
      using Buttressing Principle.
AB  - OBJECTIVE: The objective of the study was to assess the outcome of Salter- Harris
      type III distal radius fracture fixed using the principle of buttressing and
      avoiding screw insertion through the physis. MATERIALS AND METHOD: Eight school
      going children in the age group of 11-16 years with volar Barton fractures were
      treated with a volar plate using the buttress principle without inserting screws
      in the distal fragment. Patients were evaluated over a period of 18 months.
      Clinical evaluation was done using the Green O'Brien criteria and radiological
      evaluation using the Sarmiento criteria. RESULTS: The average union time was two
      months. All the patients had good to excellent functional outcome with full
      extension and flexion. CONCLUSION: Buttress plating of volar Barton fractures in
      the adolescent age group is an excellent technique to achieve satisfactory
      outcome without violation of the physis.

PMID- 28435611
TI  - Giant Chondrosarcoma of Proximal Humerus in an Adult Female Patient: A Case
      Report.
AB  - Chondrosarcoma is the third most common primary tumour of the bone, after myeloma
      and osteosarcoma. Most of the chondrosarcoma grow slowly and rarely metastasize,
      and they have an excellent prognosis after adequate surgery. However most of them
      are chemo or radio-resistant. We report a case of primary chondrosarcoma of
      proximal humerus in a 36-year-old female who presented with a six years history
      of left shoulder swelling and restricted range of motion. Trucut biopsy showed a
      well-differentiated chondrosarcoma. The patient underwent forequarter amputation
      of left upper limb and was started on chemotherapy following operation.

PMID- 28435612
TI  - The Flail and Pulseless Upper Limb: an Extreme Case of Traumatic Scapulo-thoracic
      Dissociation.
AB  - Scapulo-thoracic dissociation is an infrequent injury resulting from high energy
      trauma which is often associated with severe neurological and vascular injuries
      which may be unrecognised at the time of presentation. A 24 year-old female
      presented with bilateral rib fractures, pneumothorax, liver and kidney injuries
      following a road traffic accident. She also sustained fractures of her right
      scapula, odontoid, right transverse processes of the thoracic and lumbar
      vertebrae and a closed fracture of her right femur. Her right upper limb was
      later noted to be flail and pulseless, due to complete right brachial plexus
      injury, scapula-thoracic dissociation and subclavian artery avulsion. We managed
      the upper limb injuries non-operatively, and focused on resuscitation of the
      patient. Early exploration of the complete brachial plexus injury was not
      undertaken in spite of the possible associated poor functional outcome as there
      was no life-threatening indication.

PMID- 28435613
TI  - Bedside Continuous Irrigation and Drainage as an Interim Local Treatment for
      Septic Arthritis of the Knee in the Medically Unstable Patient: A Case Report.
AB  - Septic arthritis is a surgical emergency. Prompt diagnosis and immediate
      treatment reduce the destruction of articular cartilage and give better outcome.
      We describe a simple, minimally invasive closed tube irrigation system for the
      initial treatment of septic arthritis of the knee in a patient with complex
      medical problems who was unfit to undergo surgery.

PMID- 28435614
TI  - Time-resolved biophysical approaches to nucleocytoplasmic transport.
AB  - Molecules are continuously shuttling across the nuclear envelope barrier that
      separates the nucleus from the cytoplasm. Instead of being just a barrier to
      diffusion, the nuclear envelope is rather a complex filter that provides
      eukaryotes with an elaborate spatiotemporal regulation of fundamental molecular
      processes, such as gene expression and protein translation. Given the highly
      dynamic nature of nucleocytoplasmic transport, during the past few decades large
      efforts were devoted to the development and application of time resolved,
      fluorescence-based, biophysical methods to capture the details of molecular
      motion across the nuclear envelope. These methods are here divided into three
      major classes, according to the differences in the way they report on the
      molecular process of nucleocytoplasmic transport. In detail, the first class
      encompasses those methods based on the perturbation of the fluorescence signal,
      also known as ensemble-averaging methods, which average the behavior of many
      molecules (across many pores). The second class comprises those methods based on
      the localization of single fluorescently-labelled molecules and tracking of their
      position in space and time, potentially across single pores. Finally, the third
      class encompasses methods based on the statistical analysis of spontaneous
      fluorescence fluctuations out of the equilibrium or stationary state of the
      system. In this case, the behavior of single molecules is probed in presence of
      many similarly-labelled molecules, without dwelling on any of them. Here these
      three classes, with their respective pros and cons as well as their main
      applications to nucleocytoplasmic shuttling will be briefly reviewed and
      discussed.

PMID- 28435615
TI  - Effect of zirconia surface treatment using nitric acid-hydrofluoric acid on the
      shear bond strengths of resin cements.
AB  - PURPOSE: The aim of this study was to compare the surface roughness of zirconia
      when using Zircos E etching system (ZSAT), applying a nitric acid-hydrofluoric
      acid compound as a pretreatment agent, and also to compare the shear bonding
      strength according to different resin cements. MATERIALS AND METHODS: ZSAT, air
      abrasion, and tribochemical silicacoating were applied on prepared 120 zirconia
      specimens (10 mm in diameter, 7 mm in height) using CAD/CAM. Each 12 specimens
      with 4 different resin cements (Panavia F 2.0, Rely X Unicem, Superbond C&B, and
      Hot bond) were applied to test interfacial bond strength. The statistical
      analysis was performed using SAS 9.1 (SAS Institute Inc., Cary, NC, USA). The
      results are as follows: after application of the ZSAT on the zirconia specimens,
      surface roughness value after 2-hour etching was higher than those after 1- and 3
      hour etching on SEM images. RESULTS: For Superbond C&B and Rely X Unicem, the
      specimens treated with ZSAT showed higher shear bond strength values than those
      treated with air abrasion and tribochemical silicacoating system. Regarding the
      failure mode of interface over cement and zirconia surface, Rely X Unicem and Hot
      bond showed cohesive failures and Panavia F 2.0 and Superbond C&B showed mixed
      failures. CONCLUSION: Zircos E etching system in zirconia restoration could
      increase its shear bond strength. However, its long term success rate and
      clinical application should be further evaluated.

PMID- 28435616
TI  - Tooth surface treatment strategies for adhesive cementation.
AB  - PURPOSE: The aim of this study was to evaluate the effect of tooth surface pre
      treatment steps on shear bond strength, which is essential for understanding the
      adhesive cementation process. MATERIALS AND METHODS: Shear bond strengths of
      different cements with various tooth surface treatments (none, etching, priming,
      or etching and priming) on enamel and dentin of human teeth were measured using
      the Swiss shear test design. Three adhesives (Permaflo DC, Panavia F 2.0, and
      Panavia V5) and one self-adhesive cement (Panavia SA plus) were included in this
      study. The interface of the cement and the tooth surface with the different pre
      treatments was analyzed using SEM. pH values of the cements and primers were
      measured. RESULTS: The highest bond strength values for all cements were achieved
      with etching and primer on enamel (25.6 +/- 5.3 - 32.3 +/- 10.4 MPa). On dentin,
      etching and priming produced the highest bond strength values for all cements
      (8.6 +/- 2.9 - 11.7 +/- 3.5 MPa) except for Panavia V5, which achieved
      significantly higher bond strengths when pre-treated with primer only (15.3 +/-
      4.1 MPa). Shear bond strength values were correlated with the micro-retentive
      surface topography of enamel and the tag length on dentin except for Panavia V5,
      which revealed the highest bond strength with primer application only without
      etching, resulting in short but sturdy tags. CONCLUSION: The highest bond
      strength can be achieved for Panavia F 2.0, Permaflo DC, and Panavia SA plus when
      the tooth substrate is previously etched and the respective primer is applied.
      The new cement Panavia V5 displayed low technique-sensitivity and attained
      significantly higher adhesion of all tested cements to dentin when only primer
      was applied.

PMID- 28435618
TI  - Comparative study of abutment screw loosening with or without adhesive material.
AB  - PURPOSE: The purpose of this study was to achieve more retention and stability
      and to delay or prevent screw loosening. MATERIALS AND METHODS: Twenty implants
      (Implantium 3.4 mm, Dentium, Seoul, Korea) were divided into 2 groups (n = 20).
      In the first group, an adhesive material was applied around the screw of the
      abutments (test group). In the second group, the screws are soaked in saliva
      (control group). All the screws were torqued under 30 N/cm, Then, the samples
      were gone through a cyclic fatigue loading process. After cyclic loading, we
      detorqued screws and calculated detorque value. RESULTS: In comparison with the
      control group, all the implant screws in the test group were smeared with the
      adhesive material, showing significant higher detorque value. CONCLUSION: There
      are significantly higher detorque values in the group with adhesive. It is
      recommended to make biocompatible adhesive to reduce screw loosening.

PMID- 28435617
TI  - Analysis of the width ratio and wear rate of maxillary anterior teeth in the
      Korean population.
AB  - PURPOSE: The purpose of this study was to compare the width ratio of maxillary
      anterior teeth according to age in the Korean population and to evaluate the
      maxillary central incisor width-to-length (W/L) ratio, given differences in age
      and gender. MATERIALS AND METHODS: Ninety-three Korean adults were divided into 3
      groups (n = 31) by age. Group I was 20 - 39 years old, Group II was 40 - 59 years
      old, and Group III was over 60 years of age. After taking an impression and a
      cast model of the maxillary arch, the anterior teeth width ratio and central
      incisor W/L ratio were calculated from standard digital images of the cast models
      using a graph paper with a digital single lens reflex (DSLR) camera. The
      calculated ratios were compared among all groups and central incisor W/L ratio
      were analyzed according to age and gender. All comparative data were
      statistically analyzed with one-sample t-tests, one-way ANOVAs with Tukey tests,
      and independent t-tests. RESULTS: No significant differences in maxillary
      anterior teeth ratios were found among the age groups. The maxillary central
      incisor W/L ratios in Group III were the greatest and were significantly higher
      than those in the other groups. The central incisor W/L ratio of men was higher
      than that of women in Group II. CONCLUSION: Maxillary anterior teeth width ratios
      were similar in all age groups in the Korean population. The maxillary central
      incisor was observed as worn teeth in the group over 60 years of age, and a
      significant difference between genders was found in 40 to 50 year olds.

PMID- 28435619
TI  - Acid etching of glass-infiltrated zirconia and its biological response.
AB  - PURPOSE: The purpose of this study was to evaluate the influence of acid etching
      treatment on surface characteristics and biological response of glass-infiltrated
      zirconia. MATERIALS AND METHODS: A hundred zirconia specimens were divided into
      four groups depending on surface treatments: untreated zirconia (group Z); acid
      etched zirconia (group ZE); glass-infiltrated zirconia (group ZG); and glass
      infiltrated and acid-etched zirconia (group ZGE). Surface roughness, surface
      topography, surface morphology, and Vickers hardness of specimens were evaluated.
      For biological response test, MC3T3-E1 cell attachment and proliferation on
      surface of the specimens were examined. The data were statistically analyzed
      using one-way ANOVA and Tukey's HSD test at a significance level of 0.05.
      RESULTS: Group ZGE showed the highest surface roughness (Ra = 1.54 um) compared
      with other groups (P < .05). Meanwhile, the hardness of group Z was significantly
      higher than those of other groups (P < .05). Cell attachment and cell
      proliferation were significantly higher in group ZGE (P < .05). CONCLUSION: We
      concluded that effective surface roughness on zirconia could be made by acid
      etching treatment after glass infiltration. This surface showed significantly
      enhanced osteoblast cell response.

PMID- 28435620
TI  - The effect of resin cement type and cleaning method on the shear bond strength of
      resin cements for recementing restorations.
AB  - PURPOSE: This laboratory study assessed the effect of different dentin cleaning
      procedures on shear bond strength of resin cements for recementing prosthesis.
      MATERIALS AND METHODS: 4 * 4 flat surface was prepared on the labial surface of
      52 maxillary central incisors. Metal frames (4 * 4 * 1.5 mm) were cast with
      nickel-chromium alloy. All specimens were randomly divided into 2 groups to be
      cemented with either Panavia F2.0 (P) or RelyX Ultimate (U) cement. The initial
      shear bond strength was recorded by Universal Testing Machine at a crosshead
      speed of 0.5 mm/min. Debonded specimens were randomly allocated into 2 subgroups
      (n = 13) according to the dentin cleaning procedures for recementation. The
      residual cement on bonded dentin surfaces was eliminated with either pumice
      slurry (p) or tungsten carbide bur (c). The restorations were rebonded with the
      same cement and were subjected to shear test. Data failed the normality test (P <
      .05), thus were analyzed with Mann Whitney U-test, Wilcoxon signed rank test, and
      two-way ANOVA after logarithmic transformation (alpha = .05). RESULTS: The
      initial shear bond strength of group P was significantly higher than group U (P =
      .001). Pc and Uc groups presented higher bond strength after recementation
      compared to the initial bond strength. However, it was significant only in Pc
      group (P = .034). CONCLUSION: The specimens recemented with Panavia F2.0 provided
      higher bond strength than RelyX Ultimate cement. Moreover, a tungsten carbide bur
      was a more efficient method in removing the residual resin cement and increased
      the bond strength of Panavia F2.0 cement after recementation.

PMID- 28435621
TI  - The effect of plasma on shear bond strength between resin cement and colored
      zirconia.
AB  - PURPOSE: To investigate the effect of non-thermal atmospheric pressure plasma
      (NTAPP) treatment on shear bond strength (SBS) between resin cement and colored
      zirconia made with metal chlorides. MATERIALS AND METHODS: 60 zirconia specimens
      were divided into 3 groups using coloring liquid. Each group was divided again
      into 2 sub-groups using plasma treatment; the experimental group was treated with
      plasma, and the control group was untreated. The sub-groups were: N (non
      colored), C (0.1 wt% aqueous chromium chloride solution), M (0.1 wt% aqueous
      molybdenum chloride solution), NP (non-colored with plasma), CP (0.1 wt% aqueous
      chromium chloride solution with plasma), and MP (0.1 wt% aqueous molybdenum
      chloride solution with plasma). Composite resin cylinders were bonded to zirconia
      specimens with MDP-based resin cement, and SBS was measured using a universal
      testing machine. All data was analyzed statistically using a 2-way ANOVA test and
      a Tukey test. RESULTS: SBS significantly increased when specimens were treated
      with NTAPP regardless of coloring (P<.001). Colored zirconia containing
      molybdenum showed the highest value of SBS, regardless of NTAPP. The molybdenum
      group showed the highest SBS, whereas the chromium group showed the lowest.
      CONCLUSION: NTAPP may increase the SBS of colored zirconia and resin cement. The
      NTAPP effect on SBS is not influenced by the presence of zirconia coloring.

PMID- 28435622
TI  - Role of span length in the adaptation of implant-supported cobalt chromium
      frameworks fabricated by three techniques.
AB  - PURPOSE: This study evaluated the effect of span length on the adaptation of
      implant-supported cobalt chromium frameworks fabricated by three techniques.
      MATERIALS AND METHODS: Models with two solid abutment analogs at different inter
      abutment distances were digitized using a laboratory scanner. Frameworks of two-,
      three-, and four-unit fixed prostheses were designed by a computer. Six dots with
      a diameter of 0.2 mm were preset on the surface of each framework. A total of 54
      implant-supported cobalt chromium frameworks were fabricated by milling,
      selective laser melting (SLM), and cast techniques. The frameworks were scanned
      and exported as Stereolithography files. Distances between two dots in X, Y, and
      Z coordinates were measured in both the designed and fabricated frameworks.
      Marginal gaps between the framework and the abutments were also evaluated by
      impression replica method. RESULTS: In terms of distance measurement, significant
      differences were found between three- and four-unit frameworks, as well as
      between two- and four-unit frameworks prepared by milling technique (P<.05).
      Significant differences were also noted between two- and three-unit frameworks,
      as well as between two- and four-unit frameworks prepared by cast technique
      (P<.05). The milling technique presented smaller differences than the SLM
      technique, and the SLM technique showed smaller differences than the cast
      technique at any unit prostheses (P<.05). Evaluation with the impression replica
      method indicated significant differences among the span lengths for any
      fabrication method (P<.05), as well as among the fabrication methods at any unit
      prostheses (P<.05). CONCLUSION: The adaptation of implant-supported cobalt
      chromium frameworks was affected by the span length and fabrication method.

PMID- 28435623
TI  - Influence of nano-structured alumina coating on shear bond strength between Y-TZP
      ceramic and various dual-cured resin cements.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of nano-structured
      alumina surface coating on shear bond strength between Y-TZP ceramic and various
      dual-cured resin cements. MATERIALS AND METHODS: A total of 90 disk-shaped
      zirconia specimens (HASS CO., Gangneung, Korea) were divided into three groups by
      surface treatment method: (1) airborne particle abrasion, (2) tribochemicalsilica
      coating, and (3) nano-structured alumina coating. Each group was categorized into
      three subgroups of ten specimens and bonded with three different types of dual
      cured resin cements. After thermocycling, shear bond strength was measured and
      failure modes were observed through FE-SEM. Two-way ANOVA and the Tukey's HSD
      test were performed to determine the effects of surface treatment method and type
      of cement on bond strength (P<.05). To confirm the correlation of surface
      treatment and failure mode, the Chi-square test was used. RESULTS: Groups treated
      with the nanostructured alumina coating showed significantly higher shear bond
      strength compared to other groups treated with airborne particle abrasion or
      tribochemical silica coating. Clearfil SA Luting showed a significantly higher
      shear bond strength compared to RelyX ARC and RelyX Unicem. The cohesive failure
      mode was observed to be dominant in the groups treated with nano-structured
      alumina coating, while the adhesive failure mode was prevalent in the groups
      treated with either airborne particle abrasion or tribochemical silica coating.
      CONCLUSION: Nano-structured alumina coating is an effective zirconia surface
      treatment method for enhancing the bond strength between Y-TZP ceramic and
      various dual-cured resin cements.

PMID- 28435624
TI  - Metal stain on monolithic zirconia restoration: A case report.
AB  - In restorative treatment using fixed dental prostheses, dentists should select
      appropriate restoration material among various types of dental materials. The
      strength, marginal fit, esthetics, wear resistance, biocompatibility, and cost
      are important factors in the choice of restoration materials. The present case
      showed a surface stain on a monolithic zirconia restoration that was due to wear
      between the monolithic zirconia restoration and the base metal alloy restoration.
      This phenomenon was confirmed by surface roughness measurement and electron probe
      micro-analysis.

PMID- 28435625
TI  - Developing Azeri aphasia screening test and preliminary validity and reliability.
AB  - Background: As there is no standard aphasia screening tool for Azeri language
      yet, the aim of this study was to develop an aphasia screening test with
      acceptable validity and reliability. Methods: The present study was conducted in
      two phases. In the first phase, by literature search, the screening test was
      designed and to obtain validity it was peer reviewed by expert panel. After
      collecting experts' ratings and comments, appropriate modifications were applied.
      For test-retest reliability in the second phase, edited test was administered in
      32 patients with brain injuries, then the retest was performed two weeks later.
      Results: The developed test had eight subscales including: A) picture
      description, B) syntax, C) linguistic reasoning, D) descriptive naming, E)
      perception of minimal pairs, F) comprehensive vocabulary, G) expressive
      vocabulary, H) verbal fluency. Each section had five questions except verbal
      fluency which had 3 items. Content validity ratio (CVR) according to Lawshe's
      approach, was 82% for the whole test. Intraclass correlation for all subscales
      were more than 0.8. Cronbach's alpha coefficient for internal reliability was
      0.901. Conclusion: This aphasia screening test seems to have acceptable
      psychometric properties. This test can probably be used in clinical setting by
      specialists.

PMID- 28435626
TI  - Modification of the Persian version of Hermans Achievement Motivation
      Questionnaire to develop an adapted scale for measuring motivation of post-stroke
      survivors in Iran.
AB  - Background: Research has shown that in order for recovery from a stroke to occur,
      motivation for recovery has been essential component of rehabilitation.
      Researchers and clinicians have tended to categorize stroke survivors
      subjectively into two groups: those who have been motivated or unmotivated,
      perhaps due to the paucity of objective measures that distinguish the groups.
      Since classification of clients based on subjective inference would be prone to
      bias, this pilot study aimed to establish a regionally validated scale that was
      adequately standardized for measuring motivation of adult post-stroke survivors
      in Iran. Methods: The Persian version of Hermans Achievement Motivation
      Questionnaire (PHAMQ) was identified as the best test for the purposes of this
      study. A multistep process was undertaken to create an adapted scale from the
      PHAMQ that focused on functional behaviors, often seen in the process of
      rehabilitation. Thus, the Adapted Achievement Motivation Questionnaire (AAMQ) was
      examined for reliability and validity. Cronbach's alpha was used for measuring
      internal consistency and expert panel opinions were sought to analyze the content
      validity of AAMQ. Results: A convenience sample of 25 stroke subjects comprised
      of 10 males and 15 females participated in this study with the mean age [(+/-
      standard deviation (SD)] 58.3 +/- 9.8 years and range of 35-72 years. Expert
      opinion regarding the relevance of AAMQ items led to provide compelling evidence
      for a 28-item AAMQ. Cronbach's alpha of 0.946 showed a perfect internal
      consistency for test items. Conclusion: This pilot study suggested that AAMQ
      could be utilized as a regionally validated scale for examining the motivational
      level of patients who have sustained strokes in Iran. Further research are
      recommended.

PMID- 28435627
TI  - Outcome of acute ischemic stroke after intra-arterial thrombolysis: A study from
      India.
AB  - Background: Intravenous recombinant tissue plasminogen activator (rt-PA) is the
      currently standard treatment of acute ischemic stroke within 4.5 hours of the
      onset of stroke. Recent studies have looked at the benefits of administration of
      intra-arterial (IA) rt-PA within 8 hours onset of symptoms. Our objective was to
      assess the outcome of stroke after administration of IA rt-PA in patients with
      acute ischemic stroke. Methods: We recruited 10 consecutive acute ischemic stroke
      patients with onset of stroke from 4.5 hours to 6.5 hours. The present study was
      conducted at Yashoda Hospital, Hyderabad, India, between January 2008 and
      December 2013. All patients underwent stroke subtyping and were administered rt
      PA. We measured the thrombolysis in cerebral infarction (TICI) score after
      thrombolysis and functional outcomes at time of admission, after 24 hours, 30,
      60, and 90 days. A good outcome was defined as modified Rankin Scale (mRS) <= 2
      after 90 days. Results: Out of 10 patients 9 were men, mean age 56.3 +/- 1.8
      years and age range from 35-68 years. On stroke subtyping, 6 (60%) patients had
      large artery atherosclerosis, 3 (30%) had a stroke of indeterminate etiology and
      1 (10%) had a stroke of other etiologies. Mean time of recanalization was 6.2 +/-
      0.5 hours, 7 (70%) patients showed major neurological improvement with a mRS
      score of <= 2 at 90 days and one patient was lost to follow-up. Conclusion: Our
      study established good outcome at 90 days after administration of IA thrombolysis
      rt-PA in acute ischemic stroke.

PMID- 28435628
TI  - Evaluation of complete functional status of patients with stroke by Functional
      Independence Measure scale on admission, discharge, and six months poststroke.
AB  - Background: To evaluate the patients with stroke by Functional Independence
      Measure (FIM) scale, at the times of admission to hospital, discharge, and six
      month poststroke, and to determine the level of improvement in patients after
      rehabilitative procedures. Methods: A total number of 108 patients with stroke
      entered the study who were admitted to neurology ward. They all received
      rehabilitation consultation, and occupational and physical therapies were
      prescribed for them. Finally, their functional status was evaluated by FIM scale.
      Results: The median (and range) of FIM scores were 86 (15-119), 102 (16-123) and
      119 (17-126) at admission, discharge, and after six-month follow-up,
      respectively. Our observations showed a significant improvement in FIM scores (P
      < 0.001). About 13, 30, and 76 percent of the patients in individual functional
      tasks of motor domain and 61, 75, and 86 percent in cognitive domain got the
      score of 6 or 7 (complete or partial independence) on admission, discharge, and
      after six months, respectively. There was a reverse correlation between age and
      FIM improvement and also duration of hospitalization (P = 0.002). Conclusion: The
      study showed that the FIM is a valid tool for evaluation of patients with stroke,
      their follow-up and tracking the disease course. Moreover, we concluded that
      patients with stroke make a significant improvement in their functional status
      overtime. The exact effect of rehabilitative procedures and comparison with no
      treatment, must be assessed in separate studies.

PMID- 28435629
TI  - Prognostic value of hemoglobin A1c in nondiabetic and diabetic patients with
      acute ischemic stroke.
AB  - Background: Diabetes is a well-known risk factor for acute ischemic stroke (AIS).
      Some recent studies point to hemoglobin A1c (HbA1c) may have prognostic value in
      nondiabetic and diabetic patients with ischemic stroke (IS). The aim of this
      study was to evaluate the prognostic value of HbA1c on mortality and morbidity in
      AIS patients with and without diabetic. Methods: In this prospective
      observational study, 150 diabetic and nondiabetic patients with AIS were
      evaluated for serum HbA1c level, hypertension (HTN), hyperlipidemia, and smoking
      in the first 24 hours of admission to determine their value to predict mortality
      and mortality at 30 and 90 days. Morbidity was estimated by the National
      Institutes of Health Stroke Scale (NIHSS) and follow-up visits were scheduled 30
      and 90 days after admission. Results were analyzed with independent t-test and
      logistic regression analysis. Results: In this study, 73 patients (48.7%) were
      female and the rest were men. At 30 days, the diabetic patients had a
      significantly higher mortality, but no significant difference was found between
      diabetics and morbidity. No significant statistical differences were seen between
      HbA1c and 30 and 90 days with mortality and morbidity among diabetic patients.
      Furthermore, no significant statistical difference was seen between HbA1c and 30
      and 90 days morbidity and between HbA1c and 30 days mortality in nondiabetic
      patients. However, in nondiabetic patients, on multiple logistic regression
      analysis, a significant correlation was seen between 90 days month mortality and
      HbA1c (P = 0.002). Conclusion: HbA1c can be as a predictive biomarker in
      nondiabetic patients with AIS.

PMID- 28435630
TI  - Association of insulin-like growth factor-I with the severity and outcomes of
      acute ischemic stroke.
AB  - Background: The aim of this study was to evaluate whether higher serum levels of
      insulin-like growth factor-I (IGF-I) in the acute phase of ischemic stroke are
      associated with less severe strokes and better functional outcome in a period of
      12-month follow-up. Methods: From October 2014 to August 2015, patients with the
      diagnosis of acute ischemic stroke admitted to the stroke unit of Firoozgar
      Hospital, Tehran, Iran, entered this prospective study. National Institutes of
      Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) for stroke scores
      were used to measure the severity and outcomes of an acute ischemic stroke at the
      time of admission and 1 year after the stroke, respectively. Results: A total of
      60 acute ischemic stroke patients (28 male, 32 female) with the mean age of 71.1
      +/- 9.0 years were evaluated for the serum level of IGF-I at the time of
      admission to the stroke unit of Firoozgar Hospital. There was seen a significant
      correlation between the IGF-I serum level and the MRS scores (P = 0.020;
      correlation coefficient = -0.32). IGF-I serum level had no significant
      correlation with NIHSS scores. Conclusion: These results support that the higher
      serum levels of IGF-I at the time of stroke is associated with a significant
      better outcome in a 1-year period of follow-up. However, this hormone serum level
      seems not to have a predictable value for the ischemic stroke severity. Further
      studies are required to clarify the neuroprotective mechanisms of IGF-I in
      ischemic stroke process.

PMID- 28435631
TI  - The impact of Kinesio taping technique on children with cerebral palsy.
AB  - Cerebral palsy (CP) is the most common movement disorder in children that is
      associated with life-long disability and multiple impairments. The clinical
      manifestations of CP vary among children. CP is accompanied by a wide range of
      problems and has a broad spectrum. Children with CP demonstrate poor fine and
      dross motor function due to psychomotor disturbances. Early rehabilitation
      programs are essential for children with CP and should be appropriate for the age
      and functional condition of the patients. Kinesio taping (KT) technique is a
      relatively new technique applied in rehabilitation programs of CP. This article
      reviews the effects of KT techniques on improving motor skills in children with
      CP. In this study, we used keywords "cerebral palsy, Kinesio Tape, KT and Taping"
      in the national and international electronic databases between 1999 and 2016. Out
      of the 43 articles obtained, 21 studies met the inclusion criteria. There are
      several different applications about KT technique in children with CP. Review of
      the literature demonstrated that the impact of this technique on gross and fine
      motor function and dynamic activities is more effective than postural and static
      activities. Also this technique has more effectiveness in the child at higher
      developmental and motor stages. The majority of consistent findings showed that
      KT technique as part of a multimodal therapy program can be effective in the
      rehabilitation of children with CP to improve motor function and dynamic
      activities especially in higher developmental and motor stages.

PMID- 28435632
TI  - Anatomical considerations for insertion of pedicular screw in cervicothoracic
      junction.
AB  - Background: This study aimed to investigate the pedicle dimension and angulation
      in cervicothoracic junction (CTJ) using the findings of computed tomographic (CT)
      to help accurate insertion of pedicular screw. Methods: Forty three patients with
      high quality CT images of CTJ were evaluated. Pedicle width (PW), pedicle height
      (PH), pedicle axis length (PAL), transverse angle (TA) and sagittal angle (SA)
      were measured bilaterally from C6 to T2. Results: Mean PW was 5.3 mm at C6, 6.2
      mm at C7, 8.1 mm at T1 and 6.5 mm at T2. Males had larger pedicles than females.
      PH was greater than PW in all vertebrae. SA was relatively constant and around 15
      degrees to horizontal plane. There was high variability of vertebral
      characteristics especially in PAL and TA. Conclusion: Small diameter screws must
      be used for pedicular fixation in CTJ. Because of high variability of pedicle
      morphometry, CT scan is recommended in all patients before instrumentation.

PMID- 28435633
TI  - Neuromyelitis optica in a pregnant woman with systemic lupus erythematous: A case
      report.

PMID- 28435634
TI  - Treatment of restless legs syndrome/Willis-Ekbom disease with selenium.

PMID- 28435635
TI  - A diagnosis of stroke-like migraine attacks after radiation therapy (SMART) as
      severe headache with stroke-like presentation.

PMID- 28435637
TI  - Averting the Legacy of Kidney Disease: Focus on Childhood.
AB  - World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents
      of adult kidney disease that can begin in earliest childhood. Chronic kidney
      disease (CKD) in childhood differs from that in adults, as the largest diagnostic
      group among children includes congenital anomalies and inherited disorders, with
      glomerulopathies and kidney disease in the setting of diabetes being relatively
      uncommon. In addition, many children with acute kidney injury will ultimately
      develop sequelae that may lead to hypertension and CKD in later childhood or in
      adult life. Children born early or who are small-for-date newborns have
      relatively increased risk for the development of CKD later in life. Persons with
      a high-risk birth and early childhood history should be watched closely in order
      to help detect early signs of kidney disease in time to provide effective
      prevention or treatment. Successful therapy is feasible for advanced CKD in
      childhood; there is evidence that children fare better than adults, if they
      receive kidney replacement therapy including dialysis and transplantation, while
      only a minority of children may require this ultimate intervention. Because there
      are disparities in access to care, effort is needed so that those children with
      kidney disease, wherever they live, may be treated effectively, irrespective of
      their geographic or economic circumstances. Our hope is that World Kidney Day
      will inform the general public, policymakers and caregivers about the needs and
      possibilities surrounding kidney disease in childhood.

PMID- 28435636
TI  - The effectiveness of Orem's self-care program on headache-related disability in
      migraine patients.
AB  - Background: Providing a self-care program appropriate for patient needs in a
      supportive educative nursing system format could reduce migraine-induced
      disability. This study was designed to determine the effectiveness of Orem's self
      care program on headache related disability in migraine patients. Methods: In
      this randomized clinical trial, episodic migraine patients with or without aura
      who signed the informed consent were randomly assigned to two groups (44 patients
      each). The data collection tools included a demographic questionnaire, the
      Migraine Disability Assessment (MIDAS) questionnaire, an Orem cognition form, and
      a self-care checklist. The programs were held as four 30 to 45 minutes training
      sessions for experimental group. The MIDAS were filled out before and three
      months after program in two groups. Data were analyzed with SPSS statistical
      software, version 16 and using chi-square, Mann-Whitney and Wilcoxon tests.
      Results: There was no statistically significant difference between the two groups
      in terms of demographic variables (P > 0.05). The mean total MIDAS score in the
      experimental group, before and after the intervention was 28.1 +/- 17.5 and 6.03
      +/- 4.52, respectively (P = 0.001); and for the control group, it was 37.6 +/-
      16.4 and 55.6 +/- 14.5, respectively (P < 0.001). Also, there was a statistically
      significant difference in disability indices between the two groups after the
      intervention (P < 0.001). Conclusion: Self-care program was suitable for needs
      assessment and provided basis for acquiring positive results in order to decrease
      disability and saved patient treatment costs.

PMID- 28435638
TI  - Outcomes of Full-Right-Full-Left Split Liver Transplantation in Adults in the
      USA: A Propensity-Score Matched Analysis.
AB  - BACKGROUND: Splitting a liver for utilization in adult/pediatric recipients has
      been shown to decrease mortality on the wait list without increasing the overall
      risk of long-term graft failure compared to a whole graft. However, splitting a
      single donor organ for two adult recipients, full-right-full-left split liver
      transplantation (FRFLSLT), to overcome organ shortage is still considered
      controversial. OBJECTIVE: This study assessed the outcome of FRFLSLT comparing
      full-right (FR) and full-left (FL) with whole liver (WL) allografts in adults
      (1998-2010) using UNOS standard transplant analysis and research (STAR) file.
      Methods: Unadjusted allograft and patient survival were estimated using Kaplan
      Meier survival curves. Adjusted analyses of survival were conducted controlling
      for propensity for WL allograft. RESULTS: There were 83,313 cases of WL, 651 FR
      and 117 FL. Significant differences were evident in the unadjusted cohort between
      recipients who received FR and FL including donor, cold ischemic time, and days
      on transplant waiting list. Use of FL allograft resulted in a trend toward lower
      graft and patient survival compared to WL and FR, which was not statistically
      significant (p=0.07). In the matched cohort, FL hemiliver allograft had no
      detrimental effect on the allograft or patient survival after split liver
      transplantation when compared to FR and WL. CONCLUSION: After adjusting for donor
      and recipient characteristics, there was no difference in allograft or patient
      survival with the use of FL, FR, or WL after liver transplantation in adults.
      FRFLSLT is a valuable and safe option to expand the donor pool.

PMID- 28435639
TI  - Myocardial Performance after Successful Liver Transplantation.
AB  - BACKGROUND: Myocardial performance index (MPI) or Tei index is a Doppler-derived
      index of combined systolic and diastolic myocardial function, calculated as the
      sum of isovolumetric relaxation time (IRT) and isovolumetric contraction time
      (ICT) divided by the ejection time (ET). OBJECTIVE: To evaluate the right and
      left ventricular systolic and diastolic function using MPI in children before and
      after liver transplantation. METHODS: A cross-sectional study was conducted on 30
      children with liver cirrhosis before liver transplantation, 30 age-matched
      comparison group at least 6 months after liver transplantation, and 30 aged
      matched children without history of heart disease in Nemazi Liver Transplant
      Center, Shiraz, Iran, from April 2012 to April 2014. Echocardiographic evaluation
      was carried out with a GE Vivid 3 echocardiographic machine, using a 3-MHz probe
      with tissue Doppler imaging (TDI) software using conventional and TDI method.
      RESULTS: The mean+/-SD left ventricle Tei index in patients was 0.33+/-0.02
      before liver transplantation, 0.34+/-0.02 after liver transplantation, and 0.33+/
      003 in the comparison group (p=0.36). The mean+/-SD right ventricular Tei index
      was 0.35+/-0.04 in patients before transplantation, 0.36+/-0.46 after liver
      transplantation, and 0.28+/-0.04 in the comparison group (p<0.001). In addition,
      when TDI was used, the mean+/-SD left ventricular Tei index was 0.39+/-0.50 in
      patients before transplantation, 0.37+/-0.42 after liver transplantation, and
      0.38+/-006 in the comparison group (p=0.32). The tissue Doppler-derived Tei index
      for the right ventricle was 0.37+/-0.04 in patients before transplantation,
      0.37+/-0.04 after liver transplantation, and 0.33+/-0.05 in the comparison group
      (p=0.031). The left ventricular Doppler-derived Tei index had a significant
      (p=0.03) correlation with Child-Turcotte-Pugh (CTP) score (r=0.57). CONCLUSION:
      Left ventricular MPI with Doppler echocardiography was correlated with CTP score.
      Right ventricular MPI was significantly increased in patients with cirrhosis and
      did not improve 6 months after transplantation.

PMID- 28435640
TI  - Prevalence of Metabolic Syndrome in Liver Transplant Recipients in Iran.
AB  - BACKGROUND: Metabolic syndrome (MetSx) is common among liver transplant
      recipients. It contributes to morbidity and mortality. OBJECTIVE: To determine
      the prevalence of MetSx in patients undergoing liver transplantation (LTx) in
      Iran. METHODS: 202 liver transplant recipients of both sexes completed this
      study. Relevant information including age, sex, the underlying disease, systolic
      and diastolic blood pressure, waist circumference, fasting serum levels of blood
      sugar (FBS), triglyceride (TG), and HDL-cholesterol were measured. The prevalence
      of MetSx was evaluated at 1, 3, 6, 9, and 12 months after LTx. RESULTS: The
      prevalence of MetSx was 36.6% after 1 month that decreased to 28.2% after 12
      months of follow-up. The lowest prevalence of MetSx (27.7%) was observed 9 months
      after LTx. Our data showed a decrease in TG and an increase in HDL-C level and no
      significant changes in blood pressure, waist circumference and FBS during the
      study period. CONCLUSION: The prevalence of MetSx after LTx is high when compared
      to the normal population. It seems that a change in diet after transplantation
      may affect the prevalence of MetSx.

PMID- 28435641
TI  - Comparison of Differentiation of Induced Pluripotent Stem Cells and Bone-Marrow
      Mesenchymal Stem Cells to Osteoblast: Osteogenesis versus Pluripotency.
AB  - BACKGROUND: Derivation of induced pluripotent stem cells (iPSCs) from various
      adult somatic cells through over-expression of pluripotent genes could allow for
      the unlimited autologous supply in regenerative medicine. On the other hand the
      generation of various progenitors from bone-marrow mesenchymal stem cells (MSCs)
      is justly well established. OBJECTIVE: In this study we compared the expression
      level of pluripotent genes oct4, c-myc, sox-2, nanog, klf4 and lin28 in iPSCs and
      MSCs derived from bone marrow. Also the potential of osteogenesis of iPSCs and
      bone-marrow MSCs were compared. METHODS: We analyzed the expression level of
      oct4, sox-2, c-myc, klf4, nanog and lin28 genes in human MSCs derived from iPSCs
      and MSCs by cell culture and real-time PCR. Also the expression level of
      osteocalcin and osteopontin in both groups were evaluated. RESULTS: We found that
      the expression of osteogenic markers in differentiated iPSCs to osteoblast were
      higher than bone-marrow MSCs. While the levels of pluripotency genes oct4, c-myc
      and klf4 in iPSCs were significantly (p<0.05) higher than bone-marrow MSCs, MSCs
      showed higher expression of sox-2, nanog and lin28 compared with iPSCs (p=NS).
      CONCLUSION: It seems that the higher expression of osteopontin and osteocalcin in
      MSCs compared to iPSCs may be due to other factors (besides pluripotency)
      required for differentiation of stem cells to osteoblast.

PMID- 28435642
TI  - Dual Retro-Aortic Left Renal Vein with Drainage into Left Common Iliac Vein: Rare
      Anomaly of Left Renal Vein.
AB  - Knowledge of the renal vascular anatomy greatly contributes to the success of
      surgical, invasive and radiological procedures of the retroperitoneal region. In
      today's era of transplant, this knowledge is of utmost importance in performing
      donor nephrectomy so that number of fatal intra-operative complications can be
      prevented. Herein, we report on a rare anomaly of left renal vein in which dual
      retro-aortic left renal veins were noted and one of them drained into the left
      common iliac vein.

PMID- 28435643
TI  - Human Tissue Processing and Transplantation in MESOT States: How to Promote?
AB  - Middle East, with more than 650 million inhabitants, has one the lowest mean
      donation rate in the world in the context of organ procurement from deceased
      donors with <2 per million population as actual deceased organ donation rate in
      2014. Tissue processing and transplantation in this region are also restricted to
      a few countries among those representing Middle East Society for Organ
      Transplantation. Aiming to promote human tissue processing and transplantation in
      this region, as a life-enhancing therapeutic modality, we have to share our know
      how and facilities in order so that the patients in different countries gain
      almost equal benefit of this vital procedure. To take different infrastructure of
      Middle Eastern countries into consideration and their plans to extend their
      activities, this intention will be come to the reality and materialized by
      primarily sharing the processed tissues among member states in a centralized
      manner and to offer processing services and banking to locally retrieved tissues.

PMID- 28435644
TI  - Immunohistochemical Diagnosis of Primary Cardiac Leiomyosarcoma in a Latin
      American Patient.
AB  - Primary cardiac malignancies are rare entities. Although sarcomas enclosed the
      main group of malignant heart neoplasms, primary cardiac leiomyosarcomas are
      extremely rare and constitutes less than 8% of cardiac tumors. Leiomyosarcoma
      usually originates from the pulmonary veins and have a worm-like shaped
      structure. In this article, we present a case of a 40-year-old Hispanic man
      diagnosed with a cardiac tumor who underwent surgical resection, during
      pathological examination the tissue samples were consistent with a malignancy of
      mesenchymal origin that contained irregular bundles of spindle cells. Subsequent
      immunohistochemical study categorized the mass as a primary heart leiomyosarcoma
      with positive smooth muscle actin and muscle specific actin. As usual in this
      type of malignancy, patient's clinical status declined overtime, recurrence was
      diagnosed two months after surgery, and four months after the procedure the
      patient was discharge for palliative care.

PMID- 28435645
TI  - Angiofibrolipoma of Posterior Mediastinum with Transforaminal Extension.
AB  - Angiofibrolipoma is a histological variant of lipoma, which commonly occurs in
      subcutaneous tissues. In the present report we illustrate the case of an
      angiofibrolipoma of the posterior upper mediastinum in a 75-year-old man
      presented with progressive chest pain. Xray chest showed a homogeneous opacity
      vertically oriented along the right lateral aspect of thoracic vertebrae with an
      obtuse angle to the mediastinum. The upper extremity of the mass extended above
      the superior clavicle, suggestive of a posterior mediastinal lesion. Thoracic
      magnetic resonance imaging revealed a posterior mediastinal mass, in keeping with
      a nonaggressive lesion, with particular endocanalar extension and heterogeneous
      signal and enhancement patterns that was highly suggestive of a mixed mesenchymal
      tumor. The tumor was incompletely removed by right postero-lateral thoracotomy
      with final diagnosis of angiofibrolipoma. To the author's knowledge, such a case
      of angiofibrolipoma located in the posterior mediastinum has not been previously
      reported in the literature.

PMID- 28435646
TI  - Osteosclerosis Secondary to Metastatic Oligodendroglioma.
AB  - This paper reviews a case of metastatic 1p/19q codeleted oligodendrioglioma
      causing diffuse osteosclerosis and pain. Primary central nervous system (CNS)
      tumors rarely metastasize outside the CNS, and metastatic oligodendroglioma is
      rarer still. The patient in this study had relief of pain after being treated
      with temozolomide. We discuss this rare presentation and potential treatment
      options, and review the literature in regards to metastatic oligodendrogliomas.

PMID- 28435647
TI  - Helical Tomotherapy(r) is a Safe and Feasible Technique for Total Scalp
      Irradiation.
AB  - Angiosarcoma of the scalp is a rare aggressive tumor that affects elderly
      patients. Chemoradiation is the treatment of choice for multicentric and
      extensive disease. The shape of the scalp represents a dosimetric challenge in
      terms of achieving a homogeneous concave dose distribution with coverage of the
      entire target volume and an acceptable organs-at-risk sparing. We report a case
      of an 81-year-old man with a multifocal angiosarcoma of the scalp treated with
      Helical TomoTherapy(r) (Accuray Inc., Sunnyvale, CA, USA) intensity modulated
      radiotherapy. This technique allows precise and daily verifiable coverage of the
      target keeping the dose to the organs at risk within the constraints.

PMID- 28435648
TI  - Quality of Life in Persons with Schizophrenia.

PMID- 28435649
TI  - Improvement in Excoriation (Skin-Picking) with use of Risperidone in a Patient
      with Developmental Disability.
AB  - Patients with Autism Spectrum Disorder present with a heterogeneous mix of
      features beyond the core symptoms of the disorder. These features can be
      emotional, cognitive or behavioral. Behavioral symptoms often include self
      injury, and this may take the form of repetitive skin-picking. The prevalence of
      skin-picking disorder in Autism is unknown. Skin-picking may lead to significant
      medical and psychosocial complications. Recent data suggest that behavioral
      interventions may be more effective than medications at reducing skin-picking in
      neurotypical patients. In this case, an 11-year-old male with intellectual
      disability and autistic spectrum disorder, with self-injurious skin-picking, was
      treated with risperidone with complete resolution of skin-picking symptoms.
      risperidone has been approved for irritability and aggression in Autistic
      spectrum disorder, and may be a valuable treatment option for skin-picking in
      pediatric patients with developmental disabilities.

PMID- 28435650
TI  - Postnatal Transitional Weight Loss and Adverse Outcomes in Extremely Premature
      Neonates.
AB  - The early postnatal weight loss (EPWL) is highly variable in the extremely low
      birth weight infants (birth weight <1000 g, ELBW). It is reported to be
      unassociated with adverse outcomes within a range of 3-21% of birth weight. Its
      wide range might have contributed to this lack of association. The aim of our
      paper is to study the effects of maximum EPWL, graded as low, medium and large on
      clinical outcomes in ELBW infants. In a retrospective cohort observational study
      EPWL was measured as maximum weight loss from birth weight (MWL) in ELBW infants
      and grouped as low (5-12%) moderate (18.1-12%) and high (18-25%). The clinical
      course and complications of infants were compared between the groups. Gestational
      age (GA) was highest and surfactant administration, peak inspiratory pressure
      requirement, fluid intake, urinary output, oxygen dependent days and the number
      of oxygen dependent infants at age 28 days were lower in the low MWL compared to
      the high MWL group. However, all these significant P-values declined after
      controlling for GA. Diabetes mellitus and pregnancy associated hypertension were
      not noted in mothers in high MWL group, whereas 38% of mothers in low MWL group
      suffered from the latter (P=0.05). Maximum postnatal transitional weight loss,
      assessed in the range of low, moderate and high, is not associated with adverse
      outcomes independent of gestational age in ELBW infants. Maternal hypertension
      decreases EPWL in them.

PMID- 28435651
TI  - A Pediatric Case of Meckel Diverticulum with Uncommon Presentation Showing no
      Lower Gastrointestinal Bleeding.
AB  - Meckel's diverticulum (MD) is the most common congenital abnormality of the
      gastrointestinal tract. Painless intestinal hemorrhage is a frequently occurring
      complication that relates to MD in children. Bowel obstruction is a rare
      complication of MD in children. We report on the case of a four-year old male
      child who presented with abdominal pain and hematemesis. Finally, bowel
      obstruction due to MD was confirmed at surgery.

PMID- 28435652
TI  - Stroke in a Child with Hemoglobin SC Disease: A Case Report Describing use of
      Hydroxyurea after Transfusion Therapy.
AB  - Children with hemoglobin SC (HbSC) disease suffer a significant incidence of
      silent cerebral infarcts but stroke is rare. A 2-year-old African American boy
      with HbSC disease presented with focal neurologic deficits associated with
      magnetic resonance imaging evidence of cerebral infarction with vascular
      abnormalities. After the acute episode he was treated with monthly transfusions
      and subsequently transitioned to hydroxyurea therapy. The benefits of hydroxyurea
      as a fetal hemoglobin inducer in HbSC disease, to ameliorate clinical symptoms
      are supported by retrospective studies. This case highlights the rare occurrence
      of stroke in a child with HbSC disease and the use of hydroxyurea therapy.

PMID- 28435653
TI  - Paroxysmal Nocturnal Hemoglobinuria in the Differential Diagnosis of
      Thrombocytopenia.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a disease which diagnosis may be
      delayed due to variable clinical findings. We describe herein a case of PNH in a
      21 year old woman who admitted with complaints of chronic weakness, intermittent
      spontaneous ecchymoses, and an intermittent abdominal pain. On laboratory tests
      thrombocytopenia and iron deficiency anemia without any clinical findings were
      found. Flow cytometric evaluations showed a PNH clone of 15% for erythrocytes,
      64% for monocytes, and 60% for granulocytes. The patient was diagnosed with PNH
      and an eculizumab therapy was initiated. Following initiation of eculizumab
      therapy, the frequency of abdominal pain attacks decreased, hemoglobin level
      normalized, and platelet values increased slightly. In patients submitting with a
      triad of symptoms such as thrombocytopenia, iron deficiency anemia, and abdominal
      pain attacks of unknown etiology we suggest considering PNH. We also encourage
      physicians to share their similar observations in order to raise the knowledge on
      infrequent presentations of PNH.

PMID- 28435655
TI  - A 80-Year-Old Woman with B-Cell Prolymphocytic Leukemia.
AB  - Prolymhocytic leukemia (PLL) is a rare subtype of lymphocytic leukemias and its
      cells are immature lymphocytes. It is divided into 2 subgroups: T-PLL and B-PLL
      according to the lymphocytic origin of the cells. Discriminating B-PLL from other
      diseases with clinically-similar features is important because of the different
      treatment approaches and follow-up programs. Hereby, we report a 80-year-old
      woman presenting with fatigue, leucocytosis and mild anemia. Her peripheral blood
      smear evaluation revealed 85% prolymphocytes with moderately condensed nuclear
      chromatin, prominent nucleoli, and a faintly basophilic cytoplasm. Positron
      emission tomography-computed tomography showed mediastinal lymph nodes with
      cervical lymph nodes. There was no pathological FDG involvement in the spleen.
      Bone marrow aspiration smear exhibit atypical wide lymphocytes with prominent
      nucleoli and abundant agranular cytoplasm. Flow cytometry analysis revealed
      positive CD5+, CD19+, CD20+, CD22+, CD11c+, CD25+, CD79a+ and CD79b+.
      Fluorescence in situ hybridization technique analysis reveals no t(11;14). Bone
      marrow biopsy revealed interstitially distributed atypical cells with wide
      nucleus and prominent nucleolus.

PMID- 28435654
TI  - An Unusual Case of Primary Extranodal Lymphoma of the Gallbladder.
AB  - Primary gallbladder lymphoma is an extremely rare disease. We report a case of a
      63 year-old woman who has been admitted with gradual onset abdominal pain in the
      upper right quadrant and in the suprapubic region, nausea and malaise. According
      to the computed tomography scan of the abdomen, which was suggestive of chronic
      cholecystitis, she was treated conservatively. A laparoscopic cholecystectomy was
      performed 5 months later and the histological examination of the gallbladder
      showed a low grade small lymphocytic lymphoma. The patient has been taken over by
      the hematology team who kept her under surveillance as no further treatment was
      deemed as necessary. The purpose of this paper is to report a rare case of
      primary gallbladder lymphoma and to demonstrate that a laparoscopic
      cholecystectomy may be a valid treatment for this disease.

PMID- 28435656
TI  - White-tailed deer browse on an invasive shrub with extended leaf phenology meets
      assumptions of an apparent competition hypothesis.
AB  - It has been hypothesized that invasive plant species with extended leaf phenology
      (ELP) elevate generalist herbivore populations, increasing herbivory on native
      plants (apparent competition). This hypothesis assumes that consumption of the
      invasive is associated with periods of ELP, the invasive is a major component of
      the herbivore's diet, and that it is more nutritious than native plants during
      periods of ELP. We tested these assumptions by estimating the proportion of the
      white-tailed deer diet comprised of Lonicera maackii, an invasive shrub with ELP,
      quantifying the seasonal pattern of deer browse on this invasive shrub, and
      comparing its nutritional quality to leafless woody stems. In the Miami
      University Natural Areas in southwest Ohio we quantified the frequency of leafy
      twigs of woody species 0.3-2.1 m high in three habitats (deciduous forest,
      Juniperus virginiana forest, and forest-field edge). Monthly we quantified deer
      browse on marked L. maackii twigs, and estimated the mass of leaf and stem tissue
      consumed with allometric relationships using diameter and length of unbrowsed
      twig portions. We estimated the percent of the annual deer diet comprised of L.
      maackii by dividing the sum of these estimates by the product of deer abundance
      (estimated by pellet-based distance sampling) and consumption estimates from the
      literature. Crude protein of L. maackii stems and leaves was determined by C:N
      analyser. In each habitat the frequency of L. maackii was greater than all other
      woody species combined. We estimated L. maackii comprised 14-47 % of the annual
      deer diet. Deer browsed L. maackii each month, but consumption was high in early
      spring and late summer. Crude protein of leafy twigs of L. maackii in early
      spring was 12.9 %, much higher than leafless twigs of native species on-site.
      These findings support the assumptions of the hypothesis that invasive plants
      with ELP impact native plants via deer-mediated apparent competition.

PMID- 28435657
TI  - Palladium-Catalyzed Enantioselective Heck Alkenylation of Trisubstituted Allylic
      Alkenols: A Redox-Relay Strategy to Construct Vicinal Stereocenters.
AB  - An enantioselective, redox-relay Heck alkenylation of trisubstituted allylic
      alkenol substrates has been developed. This process enables the construction of
      vicinal stereocenters in high diastereo- and enantioselectivity and allows the
      formation of enolizable alpha-carbonyl methyl-substituted stereocenters with no
      observed epimerization under the reported reaction conditions.

PMID- 28435659
TI  - An investigative framework to facilitate epidemiological thinking during herd
      problem-solving.
AB  - Veterinary clinicians and students commonly use diagnostic approaches appropriate
      for individual cases when conducting herd problem-solving. However, these
      approaches can be problematic, in part because they make limited use of
      epidemiological principles and methods, which has clear application during the
      investigation of herd problems. In this paper, we provide an overview of
      diagnostic approaches that are used when investigating individual animal cases,
      and the challenges faced when these approaches are directly translated from the
      individual to the herd. Further, we propose an investigative framework to
      facilitate epidemiological thinking during herd problem-solving. A number of
      different approaches are used when making a diagnosis on an individual animal,
      including pattern recognition, hypothetico-deductive reasoning, and the key
      abnormality method. Methods commonly applied to individuals are often adapted for
      herd problem-solving: 'comparison with best practice' being a herd-level
      adaptation of pattern recognition, and 'differential diagnoses' a herd-level
      adaptation of hypothetico-deductive reasoning. These approaches can be effective,
      however, challenges can arise. Herds are complex; a collection of individual
      cows, but also additional layers relating to environment, management, feeding
      etc. It is unrealistic to expect seamless translation of diagnostic approaches
      from the individual to the herd. Comparison with best practice is time-consuming
      and prioritisation of actions can be problematic, whereas differential diagnoses
      can lead to 'pathogen hunting', particularly in complex cases. Epidemiology is
      the science of understanding disease in populations. The focus is on the
      population, underpinned by principles and utilising methods that seek to allow us
      to generate solid conclusions from apparently uncontrolled situations. In this
      paper, we argue for the inclusion of epidemiological principles and methods as an
      additional tool for herd problem-solving, and outline an investigative framework,
      with examples, to effectively incorporate these principles and methods with other
      diagnostic approaches during herd problem-solving. Relevant measures of
      performance are identified, and measures of case frequencies are calculated and
      compared across time, in space and among animal groupings, to identify patterns,
      clues and plausible hypotheses, consistent with potential biological processes.
      With this knowledge, the subsequent investigation (relevant on-farm activities,
      diagnostic testing and other examinations) can be focused, and actions
      prioritised (specifically, those actions that are likely to make the greatest
      difference in addressing the problem if enacted). In our experience, this
      investigative framework is an effective teaching tool, facilitating
      epidemiological thinking among students during herd problem-solving. It is a
      generic and robust process, suited to many herd-based problems.

PMID- 28435658
TI  - Sex differences in insular cortex gyri responses to a brief static handgrip
      challenge.
AB  - BACKGROUND: Cardiovascular disease varies between sexes, suggesting male-female
      autonomic control differences. Insular gyri help coordinate autonomic regulation
      and show a sex-dependent response to a sympathetic challenge. METHODS: We
      examined sex-related insular gyral responses to a short static handgrip exercise
      challenge eliciting parasympathetic withdrawal with functional magnetic resonance
      imaging (fMRI) during four 16-s challenges (80% maximum strength) in 23 healthy
      females (age; mean +/- std 50 +/- 8 years) and 40 males (46 +/- 9 years). Heart
      rate (HR) and fMRI signals were compared with repeated measures ANOVA (P < 0.05).
      Additional analyses were performed with age and age interactions, as well as
      right-handed only subjects. RESULTS: Females showed higher resting HR than males,
      but smaller percent HR change increases to the challenges. All gyri showed fMRI
      patterns concurrent with an HR peak and decline to baseline. fMRI signals
      followed an anterior-posterior organization in both sexes, but lateralization
      varied by gyri and sex. All subjects showed greater signals in the anterior vs.
      posterior gyri (females 0.3%, males 0.15%). The middle gyri showed no
      lateralization in females but left-sided dominance in males (0.1%). The posterior
      gyri showed greater left than right activation in both sexes. The anterior-most
      gyri exhibited a prominent sex difference, with females showing a greater right
      sided activation (0.2%) vs. males displaying a greater left-sided activation
      (0.15%). Age and handedness affected a minority of findings but did not alter the
      overall pattern of results. CONCLUSIONS: The anterior insula plays a greater role
      in cardiovascular regulation than posterior areas during a predominantly
      parasympathetic withdrawal challenge, with opposite lateralization between sexes.
      In females, the left anterior-most gyrus responded distinctly from other regions
      than males. Those sex-specific structural and functional brain patterns may
      contribute over time to variations in cardiovascular disease between the sexes.

PMID- 26834984
TI  - PSFC: a Pathway Signal Flow Calculator App for Cytoscape.
AB  - Cell signaling pathways are sequences of biochemical reactions that propagate an
      input signal, such as a hormone binding to a cell-surface receptor, into the cell
      to trigger a reactive process. Assessment of pathway activities is crucial for
      determining which pathways play roles in disease versus normal conditions. To
      date various pathway flow/perturbation assessment tools are available, however
      they are constrained to specific algorithms and specific data types. There are no
      accepted standards for evaluation of pathway activities or simulation of flow
      propagation events in pathways, and the results of different software are
      difficult to compare. Here we present Pathway Signal Flow Calculator (PSFC), a
      Cytoscape app for calculation of a pathway signal flow based on the pathway
      topology and node input data. The app provides a rich framework for customization
      of different signal flow algorithms to allow users to apply various approaches
      within a single computational framework.

PMID- 27239273
TI  - How blockchain-timestamped protocols could improve the trustworthiness of medical
      science.
AB  - Trust in scientific research is diminished by evidence that data are being
      manipulated. Outcome switching, data dredging and selective publication are some
      of the problems that undermine the integrity of published research. Methods for
      using blockchain to provide proof of pre-specified endpoints in clinical trial
      protocols were first reported by Carlisle. We wished to empirically test such an
      approach using a clinical trial protocol where outcome switching has previously
      been reported. Here we confirm the use of blockchain as a low cost, independently
      verifiable method to audit and confirm the reliability of scientific studies.

PMID- 28435662
TI  - Crafting minds and communities with Minecraft.
AB  - Minecraft is a first-person perspective video game in which players roam freely
      in a large three-dimensional environment. Players mine the landscape for minerals
      and use these minerals to create structures ( e.g., houses) and mould the
      landscape. But can Minecraft be used to craft communities and minds? In this
      opinion piece, we highlight the enormous potential of Minecraft for fostering
      social connectedness, collaboration, and its potential as an educational tool. We
      highlight the recent use of Minecraft to aid socialization in individuals with
      Autistic Spectrum Disorder (ASD) and promote civic engagement via the United
      Nations Human Settlement Program. We further discuss the potential for the
      recently released Minecraft: Education Edition and provide novel links between
      Minecraft and recent on work on the role of social cures and community
      empowerment in enhancing mental health, wellbeing, and resilience.

PMID- 28163899
TI  - Matching target dose to target organ.
AB  - In vitro assays have become a mainstay of modern approaches to toxicology with
      the promise of replacing or reducing the number of in vivo tests required to
      establish benchmark doses, as well as increasing mechanistic understanding.
      However, matching target dose to target organ is an often overlooked aspect of in
      vitro assays, and the calibration of in vitro exposure against in vivo benchmark
      doses is often ignored, inadvertently or otherwise.  An example of this was
      recently published in Environmental Health Perspectives by Wagner et al (2016),
      where neural stems cells were used to model the molecular toxicity of lead.  On
      closer examination of the in vitro work, the doses used in media reflected in
      vivo lead doses that would be at the highest end of lead toxicity, perhaps even
      lethal.  Here we discuss the doses used and suggest more realistic doses for
      future work with stem cells or other neuronal cell lines.

PMID- 28435664
TI  - Age-specific acceleration in malignant melanoma.
AB  - Background: The overall incidence of melanoma has increased steadily for several
      years. The relative change in incidence at different ages has not been fully
      described.  Objective: To describe how incidence at different ages has changed
      over time and to consider what aspects of tumour biology may explain the observed
      pattern of change in incidence.  Methods: The slope of incidence vs age measures
      the acceleration of cancer incidence with age. We described the pattern of change
      over time in the overall incidence of melanoma, as well as in acceleration. We
      used data for males and females from 3 different countries in the 17 sequential 5
      year birth-cohort categories from 1895-99 to 1975-79, from which we derived the
      incidence patterns.  Results: Over time, there has been a tendency for the
      overall incidence of melanoma to increase and for the acceleration (slope) of the
      age-incidence curves to decline. The changing patterns of melanoma incidence and
      acceleration differ between males and females and between the countries analysed.
      Conclusions: The observed pattern in melanoma of rising incidence and declining
      acceleration occurs in other cancers in response to genetic knockouts of
      mechanisms that protect against cancer. Perhaps some protective mechanism with
      respect to melanoma may be less effective now than in the past, possibly because
      of more intense environmental challenges.

PMID- 28435665
TI  - A voltage-dependent fluorescent indicator for optogenetic applications,
      archaerhodopsin-3: Structure and optical properties from in silico modeling.
AB  - It was demonstrated in recent studies that some rhodopsins can be used in
      optogenetics as fluorescent indicators of membrane voltage. One of the promising
      candidates for these applications is archaerhodopsin-3. However, the fluorescent
      signal for wild-type achaerhodopsin-3 is not strong enough for real applications.
      Rational design of mutants with an improved signal is an important task, which
      requires both experimental and theoretical studies. Herein, we used a homology
      based computational approach to predict the three-dimensional structure of
      archaerhodopsin-3, and a Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid
      approach with high-level multireference ab initio methodology (SORCI+Q/AMBER) to
      model optical properties of this protein. We demonstrated that this methodology
      allows for reliable prediction of structure and spectral properties of
      archaerhodopsin-3. The results of this study can be utilized for computational
      molecular design of efficient fluorescent indicators of membrane voltage for
      modern optogenetics on the basis of archaerhodopsin-3.

PMID- 28435666
TI  - Health care and social media: What patients really understand.
AB  - Background: Low health literacy is associated with decreased patient compliance
      and worse outcomes - with clinicians increasingly relying on printed materials to
      lower such risks. Yet, many of these documents exceed recommended comprehension
      levels. Furthermore, patients look increasingly to social media (SoMe) to answer
      healthcare questions. The character limits built into Twitter encourage users to
      publish small quantities of text, which are more accessible to patients with low
      health literacy. The present authors hypothesize that SoMe posts are written at
      lower grade levels than traditional medical sources, improving patient health
      literacy. Methods: The data sample consisted of the first 100 original tweets
      from three trending medical hashtags, leading to a total of 300 tweets. The
      Flesch-Kincaid Readability Formula (FKRF) was used to derive grade level of the
      tweets. Data was analyzed via descriptive and inferential statistics. Results:
      The readability scores for the data sample had a mean grade level of 9.45. A
      notable 47.6% of tweets were above ninth grade reading level. An independent
      sample t-test comparing FKRF mean scores of different hashtags found differences
      between the means of the following: #hearthealth versus #diabetes (t = 3.15, p =
      0.002); #hearthealth versus #migraine (t = 0.09, p = 0.9); and #diabetes versus
      #migraine (t = 3.4, p = 0.001). Conclusions: Tweets from this data sample were
      written at a mean grade level of 9.45, signifying a level between the ninth and
      tenth grades. This is higher than desired, yet still better than traditional
      sources, which have been previously analyzed. Ultimately, those responsible for
      health care SoMe posts must continue to improve efforts to reach the recommended
      reading level (between the sixth and eighth grade), so as to ensure optimal
      comprehension of patients.

PMID- 28435667
TI  - Neuraxial opioids as analgesia in labour and postoperative after caesarean
      section and hysterectomy: A questionnaire survey in Sweden.
AB  - Background: Neuraxial opioids improve labour analgesia and analgesia after
      caesarean section (CS) and hysterectomy. Undesirable side effects and
      difficulties in arranging postoperative monitoring might influence the use of
      these opioids. The aim of the present survey was to assess the use of intrathecal
      and epidural morphine in gynaecology and obstetrics in Sweden. Methods: A
      questionnaire was sent to 47 anaesthesiologists at obstetric units in Sweden
      concerning the use and postoperative monitoring of morphine, sufentanil and
      fentanyl in spinal/epidural anaesthesia. Results: A total of 32 units responded
      representing 83% of annual CS in Sweden. In CS spinal anaesthesia, 20/32 units
      use intrathecal morphine, the most common dose of which was 100 MUg (17/21).
      Intrathecal fentanyl (10-20 MUg) was used by 21 units and sufentanil (2.5 -10
      MUg) by 9/32 of the responding units. In CS epidural anaesthesia, epidural
      fentanyl (50-100 MUg) or sufentanil (5-25 MUg) were commonly used (25/32), and
      12/32 clinics used epidural morphine, the majority of units used a 2 mg dose.
      Intrathecal morphine for hysterectomy was used by 20/30 units, with 200 MUg as
      the most common dose (9/32). Postoperative monitoring was organized in adherence
      to the National Guidelines; the patient is in postoperative care or an
      obstetrical ward over 2-6 hours and up-to 12 hours in an ordinary surgical ward.
      Risk of respiratory depression/difficult to monitor was a reason for not using
      intrathecal opioids. Conclusions: Neuraxial morphine is used widely in Sweden in
      CS and hysterectomy, but is still restricted in some units because of the concern
      for respiratory depression and difficulties in monitoring.

PMID- 28408978
TI  - Associative memory cells: Formation, function and perspective.
AB  - Associative learning and memory are common activities in life, and their cellular
      infrastructures constitute the basis of cognitive processes. Although neuronal
      plasticity emerges after memory formation, basic units and their working
      principles for the storage and retrieval of associated signals remain to be
      revealed. Current reports indicate that associative memory cells, through their
      mutual synapse innervations among the co-activated sensory cortices, are
      recruited to fulfill the integration, storage and retrieval of multiple
      associated signals, and serve associative thinking and logical reasoning. In this
      review, we aim to summarize associative memory cells in their formation, features
      and functional impacts.

PMID- 28435669
TI  - Reframing the science and policy of nicotine, illegal drugs and alcohol -
      conclusions of the ALICE RAP Project.
AB  - In 2013, illegal drug use was responsible for 1.8% of years of life lost in the
      European Union, alcohol was responsible for 8.2% and tobacco for 18.2%, imposing
      economic burdens in excess of 2.5% of GDP. No single European country has optimal
      governance structures for reducing the harm done by nicotine, illegal drugs and
      alcohol, and existing ones are poorly designed, fragmented, and sometimes cause
      harm. Reporting the main science and policy conclusions of a transdisciplinary
      five-year analysis of the place of addictions in Europe, researchers from 67
      scientific institutions addressed these problems by reframing an understanding of
      addictions.  A new paradigm needs to account for evolutionary evidence which
      suggests that humans are biologically predisposed to seek out drugs, and that,
      today, individuals face availability of high drug doses, consequently increasing
      the risk of harm.  New definitions need to acknowledge that the defining element
      of addictive drugs is 'heavy use over time', a concept that could replace the
      diagnostic artefact captured by the clinical term 'substance use disorder', thus
      opening the door for new substances to be considered such as sugar. Tools of
      quantitative risk assessment that recognize drugs as toxins could be further
      deployed to assess regulatory approaches to reducing harm. Re-designed governance
      of drugs requires embedding policy within a comprehensive societal well-being
      frame that encompasses a range of domains of well-being, including quality of
      life, material living conditions and sustainability over time; such a frame adds
      arguments to the inappropriateness of policies that criminalize individuals for
      using drugs and that continue to categorize certain drugs as illegal. A health
      footprint, modelled on the carbon footprint, and using quantitative measures such
      as years of life lost due to death or disability, could serve as the
      accountability tool that apportions responsibility for who and what causes drug
      related harm.

PMID- 28435670
TI  - Type-1 metabotropic glutamate receptor signaling in cerebellar Purkinje cells in
      health and disease.
AB  - The cerebellum is a brain structure involved in coordination, control, and
      learning of movements, as well as certain aspects of cognitive function. Purkinje
      cells are the sole output neurons from the cerebellar cortex and therefore play
      crucial roles in the overall function of the cerebellum. The type-1 metabotropic
      glutamate receptor (mGluR1) is a key "hub" molecule that is critically involved
      in the regulation of synaptic wiring, excitability, synaptic response, and
      synaptic plasticity of Purkinje cells. In this review, we aim to highlight how
      mGluR1 controls these events in Purkinje cells. We also describe emerging
      evidence that altered mGluR1 signaling in Purkinje cells underlies cerebellar
      dysfunctions in several clinically relevant mouse models of human ataxias.

PMID- 28435671
TI  - Cadmium sulphide quantum dots with tunable electronic properties by bacterial
      precipitation.
AB  - We present a new method to fabricate semiconducting, transition metal
      nanoparticles (NPs) with tunable bandgap energies using engineered Escherichia
      coli. These bacteria overexpress the Treponema denticola cysteine desulfhydrase
      gene to facilitate precipitation of cadmium sulphide (CdS) NPs. Analysis with
      transmission electron microscopy, X-ray diffraction, and X-ray photoelectron
      spectroscopy reveal that the bacterially precipitated NPs are agglomerates of
      mostly quantum dots, with diameters that can range from 3 to 15 nm, embedded in a
      carbon-rich matrix. Additionally, conditions for bacterial CdS precipitation can
      be tuned to produce NPs with bandgap energies that range from quantum-confined to
      bulk CdS. Furthermore, inducing precipitation at different stages of bacterial
      growth allows for control over whether the precipitation occurs intra- or
      extracellularly. This control can be critically important in utilizing bacterial
      precipitation for the environmentally-friendly fabrication of functional,
      electronic and catalytic materials. Notably, the measured photoelectrochemical
      current generated by these NPs is comparable to values reported in the literature
      and higher than that of synthesized chemical bath deposited CdS NPs. This
      suggests that bacterially precipitated CdS NPs have potential for applications
      ranging from photovoltaics to photocatalysis in hydrogen evolution.

PMID- 28435672
TI  - Tele-medicine in respiratory diseases.
AB  - Information and Communication Technologies applied to health care and advances in
      sensor and data transmission technology allowed tele-medicine based programs of
      care also for patients with respiratory diseases. Different sensors, transmission
      devices and interventions are used in tele-medicine for some indications.
      Patients suffering from Chronic Obstructive Pulmonary Disease, asthma,
      neuromuscular diseases, ventilator assisted individuals and those undergoing
      pulmonary rehabilitation programs may benefit from this approach. The legal
      problems are still unsolved. Economic advantages for health care systems, though
      potentially high, are still poorly investigated. Despite the hopes, we need more
      evidence before this modality can be considered as a real progress in the
      management of patients with respiratory diseases. On one hand, these technologies
      can improve the care of patients with difficult access to services, particularly
      those in rural/remote areas, on the other hand, there is the risk that they will
      be used only to reduce standard services in health systems of developed
      countries.

PMID- 28435673
TI  - Primate autoimmune disease models; lost for translation?
AB  - Replacement, reduction and refinement (the 3R's) are the leading principles in
      translational research with animals. To be useful a model should also be
      clinically Relevant (the 4th R). Work in a non-human primate model of multiple
      sclerosis, the experimental autoimmune encephalomyelitis model, reveals an
      inherent conflict among these 4R principles. The impossibility to harmonize all
      4R's forms a major challenge when the model is applied in preclinical drug
      development.

PMID- 28435674
TI  - The three Rs: Recruitment, Retention and Residence of leukocytes in the liver.
AB  - The composition of leukocytes in the liver is highly distinct from that of the
      blood and lymphoid organs. In particular, the liver is highly enriched in non
      conventional T cells such as natural killer T (NKT) cells, gammadelta T cells and
      mucosal-associated invariant T cells. In addition, there are significant
      populations of tissue-resident NK cells (or innate lymphoid cells (ILC1)) and
      memory CD8+ T cells. These cells are joined in conditions of inflammation by
      neutrophils, monocytes and macrophages. In recent years a multitude of studies
      have generated insights into how these cells arrest, move and remain resident in
      the liver. This new understanding has largely been due to the use of intra-vital
      microscopy to track immune cells in the liver, coupled with gene expression
      profiling and parabiosis techniques. These studies have revealed that leukocyte
      recruitment in the liver does not correspond to the classical paradigm of the
      leukocyte adhesion cascade. Rather, both lymphoid and myeloid cells have been
      found to adhere in the liver sinusoids in a platelet-dependent manner. Leukocytes
      have also been observed to patrol the hepatic sinusoids using a characteristic
      crawling motility. Moreover, T cells have been observed surveying hepatocytes for
      antigen through the unique fenestrated endothelium of the liver sinusoids,
      potentially negating the need for extravasation. In this review we highlight some
      of these recent discoveries and examine the different molecular interactions
      required for the recruitment, retention and-in some cases-residence of diverse
      leukocyte populations within the liver.

PMID- 28435676
TI  - Understanding CD8+ T-cell responses toward the native and alternate HLA-A*02:01
      restricted WT1 epitope.
AB  - The Wilms' tumor 1 (WT1) antigen is expressed in solid and hematological
      malignancies, but not healthy tissues, making it a promising target for cancer
      immunotherapies. Immunodominant WT1 epitopes, the native HLA-A2/WT1126-134
      (RMFPNAPYL) (HLA-A2/RMFPNAPYL epitope (WT1A)) and its modified variant YMFPNAPYL
      (HLA-A2/YMFPNAPYL epitope (WT1B)), can induce WT1-specific CD8+ T cells, although
      WT1B is more stably bound to HLA-A*02:01. Here, to further determine the benefits
      of those two targets, we assessed the naive precursor frequencies; immunogenicity
      and cross-reactivity of CD8+ T cells directed toward these two WT1 epitopes. Ex
      vivo naive WT1A- and WT1B-specific CD8+ T cells were detected in healthy HLA
      A*02:01+ individuals with comparable precursor frequencies (1 in 105-106) to
      other naive CD8+ T-cell pools (for example, A2/HIV-Gag77-85), but as expected,
      ~100 * lower than those found in memory populations (influenza, A2/M158-66; EBV,
      A2/BMLF1280-288). Importantly, only WT1A-specific naive precursors were detected
      in HLA-A2.1 mice. To further assess the immunogenicity and recruitment of CD8+ T
      cells responding to WT1A and WT1B, we immunized HLA-A2.1 mice with either
      peptide. WT1A immunization elicited numerically higher CD8+ T-cell responses to
      the native tumor epitope following re-stimulation, although both regimens
      produced functionally similar responses toward WT1A via cytokine analysis and
      CD107a expression. Interestingly, however, WT1B immunization generated cross
      reactive CD8+ T-cell responses to WT1A and could be further expanded by WT1A
      peptide revealing two distinct populations of single- and cross-reactive
      WT1A+CD8+ T cells with unique T-cell receptor-alphabeta gene signatures.
      Therefore, although both epitopes are immunogenic, the clinical benefits of WT1B
      vaccination remains debatable and perhaps both peptides may have separate
      clinical benefits as treatment targets.

PMID- 28435675
TI  - Microbiome effects on immunity, health and disease in the lung.
AB  - Chronic respiratory diseases, including asthma, chronic obstructive pulmonary
      disease (COPD) and cystic fibrosis (CF), are among the leading causes of
      mortality and morbidity worldwide. In the past decade, the interest in the role
      of microbiome in maintaining lung health and in respiratory diseases has grown
      exponentially. The advent of sophisticated multiomics techniques has enabled the
      identification and characterisation of microbiota and their roles in respiratory
      health and disease. Furthermore, associations between the microbiome of the lung
      and gut, as well as the immune cells and mediators that may link these two
      mucosal sites, appear to be important in the pathogenesis of lung conditions.
      Here we review the recent evidence of the role of normal gastrointestinal and
      respiratory microbiome in health and how dysbiosis affects chronic pulmonary
      diseases. The potential implications of host and environmental factors such as
      age, gender, diet and use of antibiotics on the composition and overall
      functionality of microbiome are also discussed. We summarise how microbiota may
      mediate the dynamic process of immune development and/or regulation focusing on
      recent data from both clinical human studies and translational animal studies.
      This furthers the understanding of the pathogenesis of chronic pulmonary diseases
      and may yield novel avenues for the utilisation of microbiota as potential
      therapeutic interventions.

PMID- 28435678
TI  - Screening for immune response against Dengue virus in Vietnamese non-human
      primates: implications for vaccine developers.
AB  - One of the major problems faced for the development of a vaccine against Dengue
      virus is the lack of a suitable animal model. Although non-human primates do not
      show overt signs of disease, these animals develop viremia after the infection
      and are the best model to evaluate vaccine candidates against this pathogen.
      However, for that purpose, the screening of all animals is mandatory to discard
      those with previous natural immunity. The most common technique used in the
      screening is the plaque reduction neutralization test (PRNT). However, most
      recent studies points to the cell-mediated immunity (CMI) as an important player
      in the process of controlling Dengue virus (DENV) infections. Here we presented
      the results from the screening of 55 rhesus monkeys housed in an animal breeding
      facility at Quang Ninh province, Vietnam. We evaluated the neutralizing antibody
      response by PRNT and determined the levels of interferon gamma (IFNgamma)
      secretion after the viral stimulation of monkey-peripheral blood mononuclear
      cells, by enzyme-linked immunosorbent assay (ELISA). We found no correspondence
      between PRNT and IFNgamma-ELISA. In fact, 19 animals were positive only by
      IFNgamma-ELISA. Moreover, to study the protective capacity of the CMI detected,
      three animals with positive response by IFNgamma-ELISA and negative by PRNT were
      inoculated with an infective preparation of DENV-3 and, as a result, no viremia
      was detected during 10 days after the challenge. This fact points to the
      importance of screening non-human primates through a CMI assay together with
      PRNT. This procedure should discard those false-negative cases which would be
      protected after the viral challenge in the immunization schedule.

PMID- 28435677
TI  - Control of immune cell entry through the tumour vasculature: a missing link in
      optimising melanoma immunotherapy?
AB  - Metastatic melanoma remains a fatal disease to many worldwide, even after the
      breakthrough introduction of targeted therapies such as BRAF inhibitors and
      immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With
      advances in our understanding of this disease, as well as the increasing data
      gathered from patient studies, the significance of the host immune response to
      cancer progression and response to treatment is becoming clear. More
      specifically, the presence of intratumoral CD8+ cytotoxic T-cells correlates with
      better prognosis whereas the accumulation of monocytes/macrophages and
      neutrophils in the tumour is often associated with worse prognosis. Access and
      infiltration of circulating leukocytes into the tumour is governed by adhesion
      molecules and chemokines expressed by the endothelial cells of the vasculature.
      This review focuses on the adhesion molecules and chemokines which control the
      homing of CD8+ cytotoxic T-cells, monocytes and neutrophils to peripheral
      tissues, including tumours. We discuss the role of these leukocyte subsets in
      regulating melanoma growth, and detail the mechanisms used by tumours to
      selectively recruit or exclude these leukocytes for their own advantage. In doing
      so, we bring to light an underappreciated component of tumour biology which
      should be considered in combination with current treatments to selectively alter
      the leukocyte composition of tumours and ultimately enhance treatment outcome.

PMID- 28435679
TI  - Targeting the pro-inflammatory factor CCL2 (MCP-1) with Bindarit for influenza A
      (H7N9) treatment.
AB  - Influenza A viruses are important human and animal pathogens. Seasonal influenza
      viruses cause infections every year, and occasionally zoonotic viruses emerge to
      cause pandemics with significantly higher morbidity and mortality rates. Three
      cases of laboratory confirmed human infection with avian influenza A (H7N9) virus
      were reported in 2013, and there have been several cases reported across South
      East Asia, and recently in North America. Most patients experience severe
      respiratory illness, with mortality rates approaching 40%. No vaccine is
      currently available and the use of antivirals is complicated due to the emergence
      of drug resistant strains. Thus, there is a need to identify new drugs for
      therapeutic intervention and disease control. In humans, following H7N9
      infection, there is excessive expression of pro-inflammatory factors CCL2, IL-6,
      IL-8, IFNalpha, interferon-gamma, IP-10, MIG and macrophage inflammatory protein
      1beta, which has been shown to contribute to fatal disease outcomes in mouse
      models of infection. In the current study, the potent inhibitor of CCL2
      synthesis, Bindarit, was examined as a countermeasure for H7N9-induced
      inflammation in a mouse model. Bindarit treatment of mice did not have any
      substantial therapeutic efficacy in H7N9 infection. Consequently, the results
      suggest that Bindarit may be ill-advised in the treatment of influenza H7N9
      infection.

PMID- 28435681
TI  - A hol(e)y predicament.
AB  - Endocardial cushion defects are congenital abnormalities that result in valvular
      dysfunction as well as defects (or "holes") in the septa of the heart. They are
      typically diagnosed in early infancy; presentation late in life is rare. We
      present the case of a 72-year-old female admitted to the hospital with dyspnoea
      and palpitations. She was found to have multifocal atrial tachycardia. She
      suffered cardiac arrest associated with refractory hypoxaemia that required
      mechanical ventilation and vasodilator therapy with inhaled nitric oxide.
      Echocardiography revealed a large ostium primum atrial septal defect (ASD)
      complicated by Eisenmenger syndrome. It is likely that her arrhythmia, a sequela
      from her long-standing congenital abnormality, led to sudden decompensation. In
      this case presentation, we review the aetiology, presentation, and complications
      of ASDs.

PMID- 28435680
TI  - Adiposity, CVD risk factors and testosterone: Variation by partnering status and
      residence with children in US men.
AB  - Background and objectives: In many settings, partnered, invested fathers have
      lower testosterone than single men or fathers who are not involved in caregiving.
      Reduced testosterone has been identified as a risk factor for multiple chronic
      diseases, and men's health also commonly varies by life history status. There
      have been few tests of whether variation in testosterone based on partnering and
      parenting has implications for men's health. Methodology: We analysed data from a
      US population-representative sample (NHANES) of young-to-middle aged US men (n =
      875; mean age: 29.8 years +/- 6.0 [SD]). We tested for life history status
      differences in testosterone, adiposity levels and biomarkers of cardiovascular
      disease (CVD)-risk (HDL cholesterol; triglycerides; white blood cell count
      [WBC]). Results: Partnered men residing with children (RC) had lower testosterone
      and elevated abdominal adiposity compared to never married men not residing with
      children. While they did not significantly differ for WBC or triglycerides,
      partnered RC men also had comparatively lower HDL. Partnered RC males' lower
      testosterone accounted for their relatively elevated adiposity, but testosterone,
      adiposity, and health-related covariates did not explain their relatively reduced
      HDL. Conclusions and implications: Our results linking life history status-based
      differences in testosterone and adiposity, alongside our complementary HDL
      findings, indicate that testosterone-related psychobiology might have
      implications for partnered RC men's CVD risk in the US and other similar societal
      settings. These types of socially contextualized observations of men's health and
      physiological function particularly merit incorporation in clinical discussions
      of fatherhood as a component of men's health.

PMID- 28435682
TI  - Effects of a luteinizing hormone-releasing hormone agonist on cognitive, sexual,
      and hormonal functions in patients with prostate cancer: relationship with
      testicular and adrenal androgen levels.
AB  - PURPOSE: To assess the cognitive and sexual/hormonal functioning of prostate
      cancer patients treated with a luteinizing hormone-releasing hormone (LH-RH)
      agonist, and the relationships thereof with adrenal and residual testicular
      androgen levels. MATERIALS AND METHODS: Previously, we reported the effect of a
      luteinizing hormone-releasing hormone (LH-RH) agonist on testicular and adrenal
      androgen production in patients with prostate cancer. A 6-month treatment with an
      LH-RH agonist significantly reduced testicular androgens by 90-95% and adrenal
      androgens by 26-40%. This study evaluated the changes in cognitive and
      sexual/hormonal functions in the same cohort using the Mini-Mental State
      Evaluation (MMSE) and Expanded Prostate Cancer Index Composite (EPIC)
      questionnaire, respectively. In addition, the associations of each function with
      the serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2),
      dehydroepiandrosterone-sulfate (DHEA-S), dehydroepiandrosterone (DHEA),
      androstenedione (A-dione), and cortisol levels were studied. RESULTS: Cognitive
      functions did not change significantly during the treatment. Sexual functions
      were relatively low before treatment and worsened significantly after 6 and 12
      months of treatment. Interestingly, sexual bothers were improved with the
      treatment. The treatment significantly worsened hormonal functions and bothers.
      Regarding specific items in the hormonal domains, hot flashes and body weight
      changes were the main effects of worsened hormonal function. Low levels of T and
      E2 and high levels of A-dione were associated with low MMSE scores at 6 months.
      Regarding sexual and hormonal functions, A-dione, E2, T, cortisol, and DHEA-S
      were associated with poorer functioning and bother. Especially, low T levels and
      high E2 levels were the most significant factors associated with worse sexual and
      hormonal bothers. CONCLUSION: The LH-RH agonist monotherapy worsened sexual and
      hormonal functions and hormonal bothers, but not sexual bothers or cognitive
      functions. The changes in these functions were related to the testicular and
      adrenal androgens levels.

PMID- 28435684
TI  - Comparison of the clinical characteristics and prognosis of primary versus
      secondary acute gastrointestinal injury in critically ill patients.
AB  - BACKGROUND: This prospective study compared clinical characteristics and
      prognosis between primary (P) and secondary (S) acute gastrointestinal injury
      (AGI) (P-AGI)/(S-AGI) in critically ill patients. METHODS: This was a
      prospective, single-center observational study. Patients were included if they
      had been hospitalized for at least 72 h before the AGI diagnosis. Patients were
      classified according to severity of gastrointestinal dysfunction, while P-AGI or
      S-AGI were defined according to whether the gastrointestinal system was directly
      or indirectly involved. Clinical characteristics, Acute Physiology and Chronic
      Health Evaluation (APACHE) II score, and Sepsis-related Organ Failure Assessment
      (SOFA) scores after inclusion and 28-day mortality were recorded. RESULTS:
      Altogether, 282 patients were included: P and S groups enrolled 100 and 182
      patients, respectively. The S group patients were older and showed increased
      morbidities and higher APACHE II and SOFA scores. Compared to the S group, the P
      group had a higher prevalence in abdominal distention and enteroparalysis and
      fewer patients at AGI grade I, while more patients at grade III or IV. The S
      group patients had the higher 28-day mortality. Multiple logistic regression
      analysis showed AGI grades, APACHE II score, and S-AGI independently predicted
      the odds of 28-day mortality. CONCLUSIONS: Comparing to the P-AGI patients, the S
      group patients were older, with higher APACHE II and SOFA scores. AGI grade,
      APACHE II score, and S-AGI independently predicted the odds of 28-day mortality
      in AGI patients.

PMID- 28435685
TI  - Quantification and physiological significance of the rightward shift of the V
      slope during incremental cardiopulmonary exercise testing.
AB  - BACKGROUND: Ventilatory anaerobic threshold (VAT) is frequently used as a measure
      of exercise tolerance, with the V-slope method being the standard; however, this
      needs to be visually determined. Over the years, we have observed that the V
      slope itself often appears to shift rightward before the appearance of the VAT
      (RtShift: rightward shift of V-slope). This phenomenon has long been known to
      occur during the first 1-2 min of steady-state exercise and disappears
      thereafter; it is attributed to CO2 storage, presumably in active muscle.
      However, during incremental exercise, we have observed that the RtShift persists;
      furthermore, it seems to be related to the level of VAT. Therefore, we attempted
      to objectively quantify the RtShift, and to confirm its relationship to an index
      of exercise tolerance (VAT). METHODS: This study was based on a retrospective
      analysis of data from 100 cardiopulmonary ramp exercise tests (submaximal)
      performed by patients with cardiac disease. VAT was determined with the visual V
      slope method. The horizontal distances between the diagonal R = 1 line and each
      data point on the V-slope plot to the right of R = 1 were measured; the average
      of these measurements was used as an objectively determined estimate of RtShift.
      RESULTS: The predominant portion of RtShift occurred earlier than VAT. The mean
      RtShift was 33.9 +/- 25.0 mL?min-1 VO2, whereas the mean VAT was 635 +/- 220
      mL?min-1. RtShift positively correlated with VAT (r = 718, p < 0.001), confirming
      previous visual observations. It also significantly correlated with
      DeltaVO2/Deltawork rate, a marker of oxygen uptake efficiency (r = 0.531, p <
      0.001). CONCLUSIONS: We identified that among patients with cardiac disease, V
      slope is shifted rightward to varying degrees. The objectively quantified
      rightward shift of V-slope is significantly correlated with an index of exercise
      tolerance (VAT). Furthermore, it appears to occur at even lower work rates. This
      may offer a new objective means of estimating exercise tolerance; however, its
      exact biological basis still needs to be elucidated.

PMID- 28435686
TI  - Apple dwarfing rootstocks exhibit an imbalance in carbohydrate allocation and
      reduced cell growth and metabolism.
AB  - Apple dwarfing rootstocks cause earlier shoot termination and reduced root and
      shoot mass. To identify physiological factors responsible for rootstock-induced
      growth restriction, we compared vascular-enriched gene expression between two
      dwarfing rootstocks ('M27' and 'M9') and the vigorous rootstock 'M793' using RNA
      sequencing and quantitative reverse transcriptase PCR. Differentially expressed
      genes common to both dwarfing rootstocks belonged to five main biological
      processes: (1) primary metabolism, (2) cell wall synthesis and modification, (3)
      secondary metabolism, (4) hormone signalling and response and (5) redox
      homeostasis. Genes promoting the biosynthesis of amino acids, lipids and cell
      walls were downregulated in dwarfing rootstocks, whereas genes promoting the
      breakdown of these compounds were upregulated. The only exception to this trend
      was the upregulation of starch synthesis genes in dwarfing rootstocks. Non
      structural carbohydrate analysis demonstrated that starch concentrations in 'M9'
      roots, stems and grafted 'Royal Gala' ('RG') scions were double that of
      equivalent tissues from 'RG' homo-grafted trees ('RG'/'RG'). Fructose and glucose
      concentrations were much lower in all three tissues of the 'RG'/'M9' trees.
      Together, these data indicate that dwarfing rootstocks are in a state of sugar
      depletion and reduced cellular activity despite having large starch reserves.
      Another significant finding was the over-accumulation of flavonoids and the
      downregulation of auxin influx transporters MdAUX1 and MdLAX2 in dwarfing
      rootstocks. We propose that both factors reduce polar auxin transport. The
      results of this study contribute novel information about the physiological state
      of dwarfing rootstocks.

PMID- 28435687
TI  - An evaluation of low volume high-intensity intermittent training (HIIT) for
      health risk reduction in overweight and obese men.
AB  - ?: Both sprint interval training (SIT) and high-intensity intermittent training
      (HIIT) have been described as time-efficient strategies for inducing favourable
      metabolic and cardiorespiratory adaptations in healthy and diseased participants.
      BACKGROUND: To date, little attention has been given to profiling the potential
      health benefits of HIIT or modified HIIT training within overweight and obese
      cohorts with particular focus on inflammation. Within this pilot trial, we tested
      the hypothesis that 6 sessions of HIIT performed over 2 weeks with 1-2 days' rest
      would improve aerobic capacity, glucose metabolism and inflammatory profile in an
      overweight and obese male cohort. Additionally, we profiled the potential health
      benefits of 4 HIIT sessions performed over the same period. METHODS: 18
      overweight or obese males (BMI = 31.2 +/- 3.6; VO2 = 30.3 +/- 4.4 ml.kg.min-1)
      were studied before and 72 h after HIIT. Training sessions consisted of 10 x 1
      min intervals at 90% HRpeak separated by 1 min recovery periods. Exercise was
      performed either 6 (group 1, n = 8) or 4 (group 2, n = 10) times over a 2 week
      period. RESULTS: After training no changes were detected from baseline for body
      composition, aerobic capacity, glucose metabolism or inflammatory profile (p >
      0.05) in either group. CONCLUSION: Both 6 and 4 sessions of HIIT performed over a
      2-week period are ineffective in improving selected health markers within an
      overweight and obese cohort. TRIAL REGISTRATION: This trial reports data from
      human participants and was retrospectively registered on 22/02/2017 with the
      ISRCTN registry, trial number ISRCTN90672085.

PMID- 28435688
TI  - Acute phase protein mRNA expressions and enhancement of antioxidant defense
      system in Black-meated Silkie Fowls supplemented with clove (Eugenia
      caryophyllus) extracts under the influence of chronic heat stress.
AB  - BACKGROUND: The current study investigates the anti-stress effects of clove
      (Eugenia caryophyllus) extracts (0, 200, 400, and 600 mg/kg) on serum antioxidant
      biomarkers, immune response, immunological organ growth index, and expression
      levels of acute phase proteins (APPs); ovotransferrin (OVT), ceruloplasmin (CP),
      ceruloplasmin (AGP), C-reactive protein (CRP), and serum amyloid-A (SAA) mRNA in
      the immunological organs of 63-d-old male black-meated Silkie fowls subjected to
      21 d chronic heat stress at 35 +/- 2  degrees C. RESULTS: The results
      demonstrated that clove extract supplementation in the diet of Silkie fowls
      subjected to elevated temperature (ET) improve growth performance, immune
      responses, and suppressed the activities of glutathion peroxidase (GSH-Px),
      superoxide dismutase (SOD), catalase (CAT), and thioredoxin reductase (TXNRD);
      reduced serum malonaldehyde (MDA) and glutathione (GSH) concentrations when
      compared with fowls raised under thermoneutral condition (TC). Upon chronic heat
      stress and supplementation of clove extracts, the Silkie fowls showed a linear
      increase in GSH-Px, SOD, CAT, and TXNRD activities (P = 0.01) compared with fowls
      fed diets without clove extract. ET decreased (P < 0.05) the growth index of the
      liver, spleen, bursa of Fabricius and thymus. However, the growth index of the
      liver, spleen, bursa of Fabricius and thymus increased significantly (P < 0.05)
      which corresponded to an increase in clove supplemented levels. The expression of
      OVT, CP, AGP, CRP, and SAA mRNA in the liver, spleen, bursa of Fabricius and
      thymus were elevated (P < 0.01) by ET compared with those maintained at TC.
      Nevertheless, clove mitigates heat stress-induced overexpression of OVT, CP, AGP,
      CRP and SAA mRNA in the immune organs of fowls fed 400 mg clove/kg compared to
      other groups. CONCLUSIONS: The results showed that clove extracts supplementation
      decreased oxidative stress in the heat-stressed black-meated fowls by alleviating
      negative effects of heat stress via improvement in growth performance,
      antioxidant defense mechanisms, immunity, and regulate the expression of acute
      phase genes in the liver and immunological organs.

PMID- 28435689
TI  - Feasibility of titrating PEEP to minimum elastance for mechanically ventilated
      patients.
AB  - BACKGROUND: Selecting positive end-expiratory pressure (PEEP) during mechanical
      ventilation is important, as it can influence disease progression and outcome of
      acute respiratory distress syndrome (ARDS) patients. However, there are no well
      established methods for optimizing PEEP selection due to the heterogeneity of
      ARDS. This research investigates the viability of titrating PEEP to minimum
      elastance for mechanically ventilated ARDS patients. METHODS: Ten mechanically
      ventilated ARDS patients from the Christchurch Hospital Intensive Care Unit were
      included in this study. Each patient underwent a stepwise PEEP recruitment
      manoeuvre. Airway pressure and flow data were recorded using a pneumotachometer.
      Patient-specific respiratory elastance (Ers ) and dynamic functional residual
      capacity (dFRC) at each PEEP level were calculated and compared. Optimal PEEP for
      each patient was identified by finding the minima of the PEEP-Ers profile.
      RESULTS: Median Ers and dFRC over all patients and PEEP values were 32.2 cmH2O/l
      [interquartile range (IQR) 25.0-45.9] and 0.42 l [IQR 0.11-0.87]. These wide
      ranges reflect patient heterogeneity and variable response to PEEP. The level of
      PEEP associated with minimum Ers corresponds to a high change of functional
      residual capacity, representing the balance between recruitment and minimizing
      the risk of overdistension. CONCLUSIONS: Monitoring patient-specific Ers can
      provide clinical insight to patient-specific condition and response to PEEP
      settings. The level of PEEP associated with minimum-Ers can be identified for
      each patient using a stepwise PEEP recruitment manoeuvre. This 'minimum elastance
      PEEP' may represent a patient-specific optimal setting during mechanical
      ventilation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12611001179921.

PMID- 28435690
TI  - The complex legal and ethical issues related to generic medications. Viral
      hepatitis: a case study.
AB  - The economic impact of medications is significant, with many countries unable to
      afford the essential medicines listed by the WHO. Generic medications are one
      strategy to address this issue. Generic medications are similar to but not the
      same as originator medications. They have a significant cost advantage because
      they do not require the background research and development studies to support
      registration. Consequently, they are gaining increased market share in both the
      developed and developing world. Many new medications are now licensed to generic
      manufacturers in the developing world. As a result, it is possible for patients
      to bypass regulatory and cost barriers by importing medications directly from
      generic producers. Importation of the novel hepatitis C direct-acting antiviral
      therapy into Australia before it was registered in the country is an illustrative
      case study. This review will characterise generic medications and some of the
      legal and ethical issues around their utilisation, focusing on the relevant
      players, including pharma, government, patients and doctors.

PMID- 28435691
TI  - Interrupting antiretroviral treatment in HIV cure research: scientific and
      ethical considerations.
AB  - Over the past several years there has been intense activity directed at the
      possibility of achieving remission or eradication of HIV infection. Current
      assays for the measurement of latent HIV are insufficient to demonstrate complete
      clearance of replication-competent HIV. Therefore, the ultimate test for
      assessing whether investigational interventions have resulted in HIV remission or
      eradication is to interrupt standard antiretroviral therapy (ART) in a carefully
      controlled clinical trial setting. These procedures, known as analytic treatment
      interruptions (ATIs), raise important scientific and ethical questions. The lack
      of definitive assays for measuring viral reservoirs not only makes research on
      HIV remission or cure challenging, it also affects the ability to assess risks
      from ATIs themselves. In spite of these challenges, basic ethical criteria can be
      met with careful study design and close monitoring. In this brief report we
      outline ethical standards for HIV cure research involving ATIs. These criteria
      should be revisited as the science evolves.

PMID- 28435692
TI  - A CD3/CD28 microbead-based HIV-1 viral outgrowth assay.
AB  - AIMS: Latently infected resting CD4 T cells represent a major barrier to HIV-1
      eradication efforts. The standard assays used for measuring this reservoir induce
      activation of resting CD4 T cells with either phytohaemagglutinin (PHA) with
      irradiated feeder cells, or with anti-CD3 antibodies. We designed a study to
      compare the sensitivity of a new assay (based on the stimulation of CD4 T cells
      with anti-CD3 and anti-CD28 coated microbeads) with that of the traditional PHA-
      and feeder-based viral outgrowth assay. METHODS: Resting CD4 T cells from 10 HIV
      1-infected patients on suppressive combination antiretroviral therapy (cART)
      regimens were cultured in the traditional PHA/feeders viral outgrowth assay and
      the new CD3/CD28 bead-based assay. Flow cytometry was used to assess the kinetics
      of activation of resting CD4 T cells in the two different assays. RESULTS: There
      was no significant difference in the sensitivity of the two assays. The median
      frequency of latently infected cells was 0.83 infectious units per million (IUPM)
      for the PHA/feeders assay and 0.54 IUPM with the CD3/CD28 bead-based assay.
      However, while virus was obtained from all 10 patients with the traditional
      PHA/feeders outgrowth assay, no virus was obtained from two of 10 patients with
      the novel anti-CD3/CD28 bead-based viral outgrowth assay (IUPM < 0.02).
      CONCLUSION: The new CD3/CD28 bead-based assay has comparable sensitivity to the
      PHA/feeders assay and does not require the addition of feeders, making it a
      simpler and less labour-intensive alternative to the standard PHA/feeders-based
      assay.

PMID- 28435693
TI  - The 'post-condom era' or the urgent need to provide effective contraception for
      women living with HIV.

PMID- 28435694
TI  - Highlights from the HIV Research for Prevention Conference (R4P),: 17-21 October
      2016, Chicago, IL, USA.

PMID- 28435695
TI  - Highlights of the International Congress on Drug Therapy in HIV Infection, 23-26
      October 2016, Glasgow, UK.

PMID- 28435696
TI  - Highlights from the 24th Conference on Retroviruses and Opportunistic Infections:
      13-16 February 2017, Seattle, Washington, USA.
AB  - From the 13th to 16th February 2017, researchers from around the world convened
      for the 24th annual Conference on Retroviruses and Opportunistic Infections
      (CROI) at the Washington State Convention Center in Seattle, Washington. The
      conference was organised by the International Antiviral Society-USA (IAS-USA) in
      partnership with the CROI Foundation. The conference included over 1000 oral and
      poster presentations of peer-reviewed original research as well as lectures and
      symposia featuring insights from leading basic, translational and clinical
      researchers. Highlighted here are key data presented at the conference.

PMID- 28435697
TI  - Calcium phosphates and silicon: exploring methods of incorporation.
AB  - BACKGROUND: Bioinorganics have been explored as additives to ceramic bone graft
      substitutes with the aim to improve their performance in repair and regeneration
      of large bone defects. Silicon (Si), an essential trace element involved in the
      processes related to bone formation and remodeling, was shown not only to enhance
      osteoblasts proliferation but also to stimulate the differentiation of
      mesenchymal stem cells (MSCs) and preosteoblasts into the osteogenic lineage. In
      this study, the added value of Si to calcium phosphate (CaP) coatings was
      evaluated. METHODS: Tissue culture plastic well plates were coated with a thin
      CaP layer to which traces amounts of Si were added, either by adsorption or by
      incorporation through coprecipitation. The physicochemical and structural
      properties of the coatings were characterized and the dissolution behavior was
      evaluated. The adsorption/incorporation of Si was successfully achieved and
      incorporated ions were released from the CaP coatings. Human MSCs were cultured
      on the coatings to examine the effects of Si on cell proliferation and osteogenic
      differentiation. For the statistical analysis, a one-way ANOVA with Bonferroni
      post-hoc test was performed. RESULTS: The results showed that human MSCs  (hMSCs)
      responded to the presence of Si in the CaP coatings, in a dose-dependent manner.
      An increase in the expression of markers of osteogenic differentiation by human
      MSCs was observed as a result of the increase in Si concentration. CONCLUSIONS:
      The incorporation/adsorption of Si into CaP coatings was successfully achieved
      and hMSCs responded with an increase in osteogenic genes expression with the
      increase of Si concentration. Furthermore, hMSCs cultured on CaP-I coatings
      expressed higher levels of ALP and OP, indicating that this may be the preferred
      method of incorporation of bioinorganics into CaPs.

PMID- 28435698
TI  - Crystal structure of di-aqua-bis-(4-cyano-pyridine-kappaN)bis-(thio-cyanato
      kappaN)iron(II) 4-cyano-pyridine disolvate.
AB  - The asymmetric unit of the title compound, [Fe(NCS)2(C6H4N2)2(H2O)2].2C6H4N2,
      comprises one FeII cation occupying an inversion centre as well as one thio
      cyanate anion, one water mol-ecule and two 4-cyano-pyridine mol-ecules in general
      positions. The iron cations are coordinated by two N-bonded thiocyanate anions,
      two (pyridine)N-bonded 4-cyano-pyridine ligands and two water mol-ecules into
      discrete complexes. The resulting coordination polyhedron can be described as a
      slightly distorted octa-hedron. The discrete complexes are connected through
      centrosymmetric pairs of (pyridine)C-H?N(cyano) hydrogen bonds into chains that
      are further linked into a three-dimensional network through inter-molecular O-H?N
      hydrogen bonds involving the 4-cyano-pyridine solvent mol-ecules.

PMID- 28435699
TI  - Crystal structures of N-(4-chloro-phen-yl)-2-[(4,6-di-amino-pyrimidin-2-yl)sulfan
      yl]acetamide and N-(3-chloro-phen-yl)-2-[(4,6-di-amino-pyrimidin-2-yl)sulfan
      yl]acetamide.
AB  - The title compounds, C12H12ClN5OS, (I), and C12H12ClN5OS, (II), are 2-[(di-amino
      pyrimidin-2-yl)sulfan-yl]acetamides. Compound (II), crystallizes with two
      independent mol-ecules (A and B) in the asymmetric unit. In each of the mol
      ecules, in both (I) and (II), an intra-molecular N-H?N hydrogen bond forms an
      S(7) ring motif. The pyrimidine ring is inclined to the benzene ring by 42.25
      (14) degrees  in (I), and by 59.70 (16) and 62.18 (15) degrees  in mol-ecules A
      and B, respectively, of compound (II). In the crystal of (I), mol-ecules are
      linked by pairs of N-H?N hydrogen bonds, forming inversion dimers with an R22(8)
      ring motif. The dimers are linked via bifurcated N-H?O and C-H?O hydrogen bonds,
      forming corrugated layers parallel to the ac plane. In the crystal of (II), the A
      mol-ecules are linked through N-H?O and N-H?Cl hydrogen bonds, forming layers
      parallel to (100). The B mol-ecules are also linked by N-H?O and N-H?Cl hydrogen
      bonds, also forming layers parallel to (100). The parallel layers of A and B mol
      ecules are linked via N-H?N hydrogen bonds, forming a three-dimensional
      structure.

PMID- 28435700
TI  - Redetermination of the crystal structure of di-methyl-bis-[2,4-penta-nedionato(1
      )-kappa2O2,O4]tin(IV).
AB  - The redetermination of the title compound, [Sn(CH3)2(C5H7O2)2] or SnMe2(acac)2,
      from CCD data recorded at 100 K basically confirms the previous study based on
      integrated film data recorded at room temperature [Miller & Schlemper (1972 ?).
      Inorg. Chem.12, 677-681], but reveals a remarkable shrinkage of the a axis [7.12
      (1) > 6.7694 (4) A]. The mol-ecule belongs to point group Ci with the SnIV atom
      on a centre of inversion. The SnIV atom shows a slightly distorted octa-hedral
      coordination sphere with the methyl groups in trans positions and a Sn-C bond
      length of 2.115 (2) A which may serve as a standard value for an Sn-CH3 bond of
      an octa-hedrally coordinated SnIV atom. The Sn-O bonds involving the two carbonyl
      groups of the acetyl-acetonate ligand are of equal length [2.180 (1) and 2.183
      (1) A], as are the C=O [1.273 (1) and 1.274 (1) A] and C-C bond lengths [1.393
      (2) and 1.400 (2) A]. The acetyl-acetonate ligand deviates considerably from
      planarity, with a dihedral angle of 5.57 (9) degrees  between the least-squares
      planes of the two acetone moieties. The four O atoms of the two symmetry-related
      acetyl-acetonate ligands are arranged in a nearly quadratic rectangle. Weak C-H?O
      inter-actions consolidate the crystal packing.

PMID- 28435701
TI  - Crystal structure of (2E)-3-[4-(di-methyl-amino)-phen-yl]-1-(thio-phen-2-yl)prop
      2-en-1-one.
AB  - The equimolar reaction between 4-(di-methyl-amino)-benzaldehyde and 2-acetyl-thio
      phene in basic ethano-lic solution yields the title compound, C15H15NOS, whose
      mol-ecular structure matches the asymmetric unit. The mol-ecule is not planar,
      the dihedral angle between the aromatic and the thio-phene rings being 11.4 (2)
      degrees . In the crystal, mol-ecules are linked by C-H?O and weak C-H?S inter
      actions along [100], forming R22 (8) rings, and by weak C-H?O inter-actions along
      [010], forming chains with a C(6) graph-set motif. In addition, mol-ecules are
      connected into centrosymmetric dimers by weak C-H?pi inter-actions, as indicated
      by the Hirshfeld surface analysis. The most important contributions for the
      crystal structure are the H?H (46.50%) and H?C (23.40%) inter-actions. The
      crystal packing resembles a herringbone arrangement when viewed along [100]. A
      mol-ecular docking calculation of the title compound with the neuraminidase
      enzyme was carried out. The enzyme shows (ASN263)N-H?O, (PRO245)C-H?Cg(thio-phene
      ring) and (AGR287)C-H?N inter-molecular inter-actions with the title compound.
      The crystal structure was refined as a two-component twin with a fractional
      contribution to the minor domain of 0.0181 (8).

PMID- 28435702
TI  - Synthesis and crystal structure of bis-(MU-2-methyl-benzene-thiol-ato
      kappa2S:S)bis-[meth-yl(2-methyl-benzene-thiol-ato-kappaS)indium(III)].
AB  - The dinuclear title compound, [In2(CH3)2(C7H7S)4] or [Me(2-MeC6H4S)In-MU-(2
      MeC6H4S)2InMe(2-MeC6H4S)], was prepared from the 1:2 reaction of Me3In and 2
      MeC6H4SH in toluene. Its crystal structure exhibits a four-membered In2S2 ring
      core via bridging (2-MeC6H4S) groups. The dimeric units are further associated
      into a one-dimensional polymeric structure extending parallel to the a axis via
      inter-molecular In?S contacts. The In atoms are then in distorted trigonal
      bipyramidal CS4 bonding environments.

PMID- 28435703
TI  - Crystal structure of bromido-fac-tricarbon-yl[5-(3,4,5-tri-meth-oxy-phen-yl)-3
      (pyridin-2-yl)-1H-1,2,4-triazole-kappa2N2,N3]rhenium(I) methanol monosolvate.
AB  - In the title compound, [ReBr(C16H16N4O3)(CO)3].CH3OH, the ReI atom adopts a
      distorted octa-hedral coordination sphere with a facial arrangement of the three
      carbonyl ligands. Two N atoms of the chelating 5-(3,4,5-tri-meth-oxy-phen-yl)-3
      (pyridin-2-yl)-1H-1,2,4-triazole ligand and two carbonyl ligands define the
      equatorial plane of the complex, with the third carbonyl ligand and the bromide
      ligand in axial positions. Conventional hydrogen bonds including the methanol
      solvent mol-ecules assemble the complex mol-ecules through mutual N-H?O-H?Br
      links [N?O = 2.703 (3) A and O?Br = 3.255 (2) A] into centrosymmetric dimers,
      whereas weaker C-H?O and C-H?Br hydrogen bonds [C?O = 3.215 (3)-3.390 (4) A and
      C?Br = 3.927 (3) A] connect the dimers into double layers parallel to the (111)
      plane.

PMID- 28435704
TI  - A two-dimensional coordination polymer: poly[[bis-[MU2-N-ethyl-N-(pyridin-4
      ylmeth-yl)di-thio-carbamato-kappa3N:S,S']cadmium(II)] 3-methyl-pyridine
      monosolvate].
AB  - The title compound, {[Cd(C9H11N2S2)2].C6H7N} n , features two MU2-kappa3-di-thio
      carbamate ligands each of which chelates one CdII atom, via the S atoms, while
      simultaneously bridging to another via the pyridyl-N atom. The result is a two
      dimensional coordination polymer extending parallel to the ab plane with square
      channels along the b axis. The CdII atom geometry is based on a distorted cis
      N2S4 octa-hedron. The 3-methyl-pyridine mol-ecules reside in the channels aligned
      along the b axis, being held in place by methyl-ene-C-H?N(3-methyl-pyridine) and
      (3-methyl-pyridine)-C-H?pi(pyrid-yl) inter-actions. Pyridyl-C-H?S and di-thio
      carbamate-methyl-C-H?pi(pyrid-yl) inter-actions provide connections between
      layers along the c axis.

PMID- 28435705
TI  - A triclinic polymorph of tri-cyclo-hexyl-phosphane sulfide: crystal structure and
      Hirshfeld surface analysis.
AB  - The title compound, (C6H11)3PS (systematic name: tri-cyclo-hexyl-lambda5
      phosphane-thione), is a triclinic (P-1, Z' = 1) polymorph of the previously
      reported ortho-rhom-bic form (Pnma, Z' = 1/2) [Kerr et al. (1977 ?). Can. J.
      Chem. 55, 3081-3085; Reibenspies et al. (1996 ?). Z. Kristallogr. 211, 400].
      While conformational differences exist between the non-symmetric mol-ecule in the
      triclinic polymorph, cf. the mirror-symmetric mol-ecule in the ortho-rhom-bic
      form, these differences are not chemically significant. The major feature of the
      mol-ecular packing in the triclinic polymorph is the formation of linear chains
      along the a axis sustained by methine-C-H?S(thione) inter-actions. The chains
      pack with no directional inter-actions between them. The analysis of the
      Hirshfeld surface for both polymorphs indicates a high degree of similarity,
      being dominated by H?H (ca 90%) and S?H/H?S contacts.

PMID- 28435706
TI  - Substitution of indium for chromium in TlIn5-x Cr x Se8: crystal structure of
      TlIn4.811(5)Cr0.189(5)Se8.
AB  - The new thallium penta-(indium/chromium) octa-selenide,
      TlIn4.811(5)Cr0.189(5)Se8, has been synthesized by solid-state reaction. It
      crystallizes isotypically with TlIn5Se8 in the space group C2/m. Although the two
      Tl positions are disordered and only partially occupied, no Tl deficiency was
      observed. The insertion of chromium in the structure has been confirmed by EDS
      analysis. Chromium substitutes indium exclusively at one of three In sites, viz.
      at one of the positions with site symmetry 2/m (Wyckoff position 2a). In the
      crystal structure, edge-sharing InSe6 octa-hedra, and (In,Cr)Se6 octa-hedra and
      InSe4 tetra-hedra make up two types of columns that are linked into a framework
      in which two different types of channels parallel to [010] are present. The Tl
      atoms are located in the larger of the channels, whereas the other, smaller
      channel remains unoccupied.

PMID- 28435707
TI  - Crystal structure of methyl (4R)-4-(4-meth-oxy-benzo-yl)-4-{[(1R)-1-phenyl-eth
      yl]carbamo-yl}butano-ate.
AB  - The title compound, C22H25NO5, was prepared by CAN [cerium(IV) ammonium nitrate]
      oxidation of the corresponding beta-lactam. The dihedral angle between the
      benzene rings is 13.3 (4) degrees  and the C-N-C(=O)-C torsion angle is 176.1 (6)
      degrees . In the crystal, amide-C(4) N-H?O and reinforcing C-H?O hydrogen bonds
      link the mol-ecules into infinite [010] chains. Further C-H?O hydrogen bonds
      cross-link the chains in the c-axis direction.

PMID- 28435708
TI  - Crystal structure of Pigment Red 254 from X-ray powder diffraction data.
AB  - The crystal structure of Pigment Red 254 [P.R. 254, C18H10Cl2N2O2; systematic
      name: 3,6-bis-(4-chloro-phen-yl)-2,5-di-hydro-pyrrolo-[3,4-c]pyrrole-1,4-dione]
      was solved from laboratory X-ray powder diffraction data using the simulated
      annealing method followed by Rietveld refinement because the very low solubility
      of the pigment in all solvents impedes the growth of single crystals suitable for
      X-ray analysis. The mol-ecule lies across an inversion center. The dihedral angle
      between the benzene ring and the pyrrole ring in the unique part of the mol-ecule
      is 11.1 (2) degrees . In the crystal, mol-ecules are linked via N-H?O hydrogen
      bonds, forming chains along [110] incorporating R22(8) rings.

PMID- 28435709
TI  - Crystal and mol-ecular structure of (2Z,5Z)-3-(2-meth-oxy-phen-yl)-2-[(2-meth-oxy
      phen-yl)imino]-5-(4-nitro-benzyl-idene)thia-zolidin-4-one.
AB  - In the title compound, C24H19N3O5S, the thia-zole ring (r.m.s. deviation = 0.012
      A) displays a planar geometry and is surrounded by three fragments, two meth-oxy
      phenyl and one nitro-phenyl. The thia-zole ring is almost in the same plane as
      the nitro-phenyl ring, making a dihedral angle of 20.92 (6) degrees . The two
      meth-oxy-phenyl groups are perpendicular to the thia-zole ring [dihedral angles
      of 79.29 (6) and 71.31 (7) degrees  and make a dihedral angle of 68.59 (7)
      degrees . The mol-ecule exists in an Z,Z conformation with respect to the C=N
      imine bond. In the crystal, a series of C-H?N, C-H?O and C-H?S hydrogen bonds,
      augmented by several pi-pi(ring) inter-actions, produce a three-dimensional
      architecture of mol-ecules stacked along the b-axis direction. The experimentally
      derived structure is compered with that calculated theoretically using DFT(B3YLP)
      methods.

PMID- 28435710
TI  - Inter-action between maleic acid and N-R-furfuryl-amines: crystal structure of 2
      methyl-N-[(5-phenyl-furan-2-yl)meth-yl]propan-2-aminium (2Z)-3-carb-oxy-acrylate
      and N-[(5-iodo-furan-2-yl)meth-yl]-2-methyl-propan-2-aminium (2Z)-3-carb-oxy-prop
      2-enoate.
AB  - The title mol-ecular salts, C15H20NO+.C4H3O4-, (I), and C9H15INO+.C4H3O4-, (II),
      have very similar mol-ecular geometries for both cation and anion. The anions of
      both (I) and (II) are practically planar (r.m.s. deviations = 0.062 and 0.072 A,
      respectively) and adopt a rare symmetrical geometry with the hy-droxy H atom
      approximately equidistant from the two O atoms. In their crystals, the cations
      and anions in both (I) and (II) form tight ionic pairs via strong N-H?O hydrogen
      bonds, with a roughly perpendicular disposition of the anion to the furan ring of
      the cation. This ion-pair conformation appears to correlate with the lack of
      reactivity of these salts in [4 + 2] cyclo-addition reactions. In the extended
      structures of (I) and (II), the ion pairs form hydrogen-bonded chains propagating
      along [010] and [001], respectively, via N-H?O hydrogen bonds.

PMID- 28435711
TI  - Tricaesium citrate monohydrate, Cs3C6H5O7.H2O: crystal structure and DFT
      comparison.
AB  - The crystal structure of tricaesium citrate monohydrate, 3Cs+.C6H5O73-.H2O, has
      been solved and refined using laboratory X-ray single-crystal diffraction data,
      and optimized using density functional techniques. This compound is isostructural
      to the K+ and Rb+ compounds with the same formula. The three independent Cs
      cations are eight-, eight-, and seven-coordinate, with bond-valence sums of 0.91,
      1.22, and 1.12 valence units. The coordination polyhedra link into a three
      dimensional framework. The hy-droxy group forms the usual S(5) hydrogen bond with
      the central carboxyl-ate group, and the water mol-ecule acts as a donor in two
      strong hydrogen bonds.

PMID- 28435712
TI  - Crystal structure and Hirshfeld surface analysis of 1-(4-chloro-phen-yl)-2-{[5-(4
      chloro-phen-yl)-1,3,4-oxa-diazol-2-yl]sulfan-yl}ethanone.
AB  - In the title compound, C16H10Cl2N2O2S, the dihedral angles formed by the chloro
      substituted benzene rings with the central oxa-diazole ring are 6.54 (9) and 6.94
      (8) degrees . In the crystal, C-H?N hydrogen bonding links the mol-ecules into
      undulating ribbons running parallel to the b axis. Hirshfeld surface analysis
      indicates that the most important contributions for the crystal packing are the
      H?C (18%), H?H (17%), H?Cl (16.6%), H?O (10.4%), H?N (8.9%) and H?S (5.9%) inter
      actions.

PMID- 28435713
TI  - Crystal structure of trans-di-chloridobis-[N-(5,5-di-methyl-4,5-di-hydro-3H
      pyrrol-2-yl-kappaN)acetamide]palladium(II) dihydrate.
AB  - The title complex, [PdCl2(C8H14N2O)2].2H2O, was obtained by N-O bond cleavage of
      the oxa-diazo-line rings of the trans-[di-chlorido-bis-(2,5,5-trimethyl-5,6,7,7a
      tetra-hydro-pyrrolo-[1,2-b][1,2,4]oxa-diazole-N1)]palladium(II) complex. The
      palladium(II) atom exhibits an almost square-planar coordination provided by two
      trans-arranged chloride anions and a nitro-gen atom from each of the two neutral
      organic ligands. In the crystal, N-H?O, O-H?O and O-H?Cl hydrogen bonds link
      complex mol-ecules into double layers parallel to the bc plane.

PMID- 28435714
TI  - Crystal structure and Hirshfeld surface analysis of ethyl 5-phenyl-isoxazole-3
      carboxyl-ate.
AB  - The title compound, C12H11NO3, is an inter-mediate used in the synthesis of many
      drug-like mol-ecules. The mol-ecule is almost planar, with the phenyl ring
      inclined to the isoxazole ring by 0.5 (1) degrees . The ester moiety has an
      extended conformation and is almost in the same plane with respect to the
      isoxazole ring, as indicated by the O-C-C-N torsion angle of -172.86 (18) degrees
      . In the crystal, mol-ecules are linked via pairs of C-H?O hydrogen bonds with
      the same acceptor atom, forming inversion dimers with two R21(7) ring motifs. The
      mol-ecules stack in layers lying parallel to (10-3). Analysis using Hirshfeld
      surface generation and two-dimensional fingerprint plots explores the
      distribution of weak inter-molecular inter-actions in the crystal structure.

PMID- 28435715
TI  - The silver(I) nitrate complex of the ligand N-(pyridin-2-ylmeth-yl)pyrazine-2
      carboxamide: a metal-organic framework (MOF) structure.
AB  - The reaction of silver(I) nitrate with the mono-substituted pyrazine carboxamide
      ligand, N-(pyridin-2-ylmeth-yl)pyrazine-2-carboxamide (L), led to the formation
      of the title compound with a metal-organic framework (MOF) structure,
      [Ag(C11H10N4O)(NO3)] n , poly[MU-nitrato-[MU-N-(pyridin-2-ylmethyl
      kappaN)pyrazine-2-carboxamide-kappaN4]silver(I)]. The silver(I) atom is
      coordinated by a pyrazine N atom, a pyridine N atom, and two O atoms of two
      symmetry-related nitrate anions. It has a fourfold N2O2 coordination sphere,
      which can be described as distorted trigonal-pyramidal. The ligands are bridged
      by the silver atoms forming -Ag-L-Ag-L- zigzag chains along the a-axis direction.
      The chains are arranged in pairs related by a twofold screw axis. They are linked
      via the nitrate anions, which bridge the silver(I) atoms in a MU2 fashion,
      forming the MOF structure. Within the framework there are N-H?O and C-H?O
      hydrogen bonds present.

PMID- 28435716
TI  - Crystal structure of 4,5-di-bromo-phenanthrene.
AB  - The synthesis and crystal structure of the title compound, C14H8Br2, is
      described. The mol-ecule is positioned on a twofold rotation axis and the
      asymmetric unit consists of half a mol-ecule with the other half being generated
      by symmetry. The presence of two large bromine atoms in the bay region
      significantly distorts the mol-ecule from planarity and the mean planes of the
      two terminal rings of the phenanthrene system are twisted away from each other by
      28.51 (14) degrees . The torsion angle between the two C-Br bonds is 74.70 (14)
      degrees  and the distance between the two Br atoms is 3.2777 (13) A. The mol
      ecules pack in layers in the crystal, with the centroids of the central rings of
      the phenanthrene units in adjacent layers separated by a distance of 4.0287 (10)
      A. These centroids are shifted by 2.266 (6) A relative to each other, indicating
      slippage in the stacking arrangement. Furthermore, the distance between the
      centroids of the terminal and central rings of the phenanthrene units in adjacent
      layers is slightly shorter at 3.7533 (19) A. While all of the mol-ecules within
      each layer are oriented in the same direction, those in adjacent layers are
      oriented in the opposite direction, leading to anti-parallel stacks.

PMID- 28435717
TI  - A cinnamaldehyde Schiff base of S-(4-methyl-benz-yl) di-thio-carbazate: crystal
      structure, Hirshfeld surface analysis and computational study.
AB  - The title di-thio-carbazate ester (I), C18H18N2S2 [systematic name: (E)-4-methyl
      benzyl 2-[(E)-3-phenyl-allyl-idene]hydrazinecarbodi-thio-ate, comprises an almost
      planar central CN2S2 residue [r.m.s. deviation = 0.0131 A]. The methyl-ene(tolyl
      4) group forms a dihedral angle of 72.25 (4) degrees  with the best plane through
      the remaining non-hydrogen atoms [r.m.s. deviation = 0.0586 A] so the mol-ecule
      approximates mirror symmetry with the 4-tolyl group bis-ected by the plane. The
      configuration about both double bonds in the N-N=C-C=C chain is E; the chain has
      an all trans conformation. In the crystal, eight-membered centrosymmetric thio
      amide synthons, {?HNCS}2, are formed via N-H?S(thione) hydrogen bonds.
      Connections between the dimers via C-H?pi inter-actions lead to a three
      dimensional architecture. A Hirshfeld surface analysis shows that (I) possesses
      an inter-action profile similar to that of a closely related analogue with an S
      bound benzyl substituent, (II). Computational chemistry indicates the dimeric
      species of (II) connected via N-H?S hydrogen bonds is about 0.94 kcal mol-1 more
      stable than that in (I).

PMID- 28435718
TI  - Crystal structure of 4,4'-di-nitro-[1,1'-biphen-yl]-2-amine.
AB  - In the title biphenyl derivative, C12H9N3O4, the dihedral angle between the
      benzene rings is 52.84 (10) degrees . The nitro group attached to the benzene
      ring is inclined to the ring by 4.03 (2) degrees , while the nitro group attached
      to the amino-substituted benzene ring is inclined to the ring by 8.84 (2) degrees
      . In the crystal, mol-ecules are linked by two pairs of N-H?O hydrogen bonds,
      forming chains propagating along [101]. Within the chains, these N-H?O hydrogen
      bonds result in the formation of R22(20) and R22(14) ring motifs. The latter ring
      motif is reinforced by a pair of C-H?O hydrogen bonds, enclosing R21(6) ring
      motifs. The chains are linked by a second C-H?O hydrogen bond, forming a three
      dimensional supra-molecular structure.

PMID- 28435719
TI  - Crystal structure of O-benzyl-l-tyrosine N-carb-oxy anhydride.
AB  - In the title compound, C17H15NO4 (alternative name; O-benzyl-l-tyrosine N-carb
      oxy anhydride), the oxazolidine ring is planer, with an r.m.s. deviation of 0.039
      A. The benz-yloxy and benzyl rings are almost coplanar, making a dihedral angle
      of 0.078 (10) degrees , and are inclined to the oxazolidine ring by 59.16 (11)
      and 58.42 (11) degrees , respectively. In the crystal, mol-ecules are linked by N
      H?O and C-H?O hydrogen bonds, forming ribbons propagating along [010]. The
      ribbons are linked by C-H?pi inter-actions, forming a three-dimensional supra
      molecular structure. The oxazolidine rings of adjacent ribbons are arranged into
      a layer parallel to the ab plane. This arrangement is favourable for the
      polymerization of the compound in the solid state.

PMID- 28435720
TI  - Ruthenium(II) carbonyl compounds with the 4'-chloro-2,2':6',2''-terpyridine
      ligand.
AB  - Two ruthenium carbonyl complexes with the 4'-chloro-2,2':6',2''-terpyridine
      ligand (tpy-Cl, C15H10ClN3), i.e. [RuCl(tpy-Cl)(CO)2][RuCl3(CO)3] (I) [systematic
      name: cis-di-carbonyl-chlorido(4'-chloro-2,2':6',2''-terpyridine
      kappa3N)ruthenium(II) fac-tricarbonyltri-chlorido-ruthenate(II)], and [RuCl2(tpy
      Cl)(CO)2] (II) [cis-dicarbonyl-trans-di-chlorido(4'-chloro-2,2':6',2''
      terpyridine-kappa2N1,N1')ruthenium(II)], were synthesized and characterized by
      single-crystal X-ray diffraction. The RuII atoms in both centrosymmetric
      structures (I) and (II) display similar, slightly distorted octa-hedral
      coordination spheres. The coordination sphere in the complex cation in compound
      (I) is defined by three N atoms of the tridentate tpy-Cl ligand, two carbonyl
      carbon atoms and one chlorido ligand; the charge is balanced by an octa-hedral
      [Ru(CO)3Cl3]- counter-anion. In the neutral compound (II), the tpy-Cl ligand
      coordinates to the metal only through two of its N atoms. The coordination sphere
      of the RuII atom is completed by two carbonyl and two chlorido ligands. In the
      crystal structures of both (I) and (II), weak C-H?Cl inter-actions are observed.

PMID- 28435721
TI  - Structure of 2,2'-(5-tert-butyl-1,3-phenyl-ene)bis-(1-pentyl-1H-benzimidazol-3
      ium) tetra-chlorido-mercurate(II).
AB  - In the title salt, (C34H44N4)[HgCl4], the [C34H44N4]2+ cations and [HgCl4]2-
      anions are linked by N-H?Cl hydrogen bonds. One of the two n-pentyl side chains
      was refined as disordered over two sets of sites, with occupancies of 0.733 (18)
      and 0.267 (18). The geometry around the HgII atom in the [HgCl4]2- anion is
      distorted tetra-hedral, with bond angles ranging from 98.16 (3) to 120.68 (3)
      degrees . In the [HgCl4]2- anion, there are two short Hg-Cl bonds [2.4120 (9) and
      2.4171 (11) A], one inter-mediate Hg-Cl bond [2.4716 (12) A] and one long Hg-Cl
      bond [2.6579 (13) A] for the Cl atom involved in a trifurcated hydrogen bond as
      an acceptor, including two N-H?Cl?H-N interactions as well as one C-H?Cl inter
      action. There are several C-H?Cl inter-actions, with C?Cl distances ranging from
      3.492 (3) to 3.796 (3) A. These link the cations and anions into a zigzag chain
      along the c-axis direction. In addition, there are Cl?Cl halogen bonds, as well
      as pi-pi inter-actions, with centroid-to-centroid distances of 3.4765 (18) A,
      which link one of the two benzimidazole moieties into dimeric units.

PMID- 28435722
TI  - 1-Butyl-1-chloro-3-methyl-3H-2,1lambda4-benzoxa-tellurole: crystal structure and
      Hirshfeld analysis.
AB  - Two independent mol-ecules comprise the asymmetric unit in the title
      benzoxatellurole compound, C12H17ClOTe. The mol-ecules, with the same chirality
      at the methine C atom, are connected into a loosely associated dimer by Te?O
      inter-actions, leading to a {?Te-O}2 core. The resultant C2ClO2 donor set
      approximates a square pyramid with the lone pair of electrons projected to occupy
      a position trans to the n-butyl substituent. Inter-estingly, the TeIV atoms
      exhibit opposite chirality. The major difference between the independent mol
      ecules relates to the conformation of the five-membered chelate rings, which is
      an envelope with the O atom being the flap, in one mol-ecule and is twisted about
      the O-C(methine) bond in the other. No directional inter-molecular inter-actions
      are noted in the mol-ecular packing beyond the aforementioned Te?O secondary
      bonding. The analysis of the Hirshfeld surface reveals the dominance of H?H
      contacts, i.e. contributing about 70% to the overall surface, and clearly
      differentiates the immediate crystalline environments of the two independent mol
      ecules in terms of both H?H and H?Cl/Cl?H contacts.

PMID- 28435723
TI  - Formamidinium iodide: crystal structure and phase transitions.
AB  - At a temperature of 100 K, CH5N2+.I- (I), crystallizes in the monoclinic space
      group P21/c. The formamidinium cation adopts a planar symmetrical structure [the
      r.m.s. deviation is 0.002 A, and the C-N bond lengths are 1.301 (7) and 1.309 (8)
      A]. The iodide anion does not lie within the cation plane, but deviates from it
      by 0.643 (10) A. The cation and anion of I form a tight ionic pair by a strong N
      H?I hydrogen bond. In the crystal of I, the tight ionic pairs form hydrogen
      bonded zigzag-like chains propagating toward [20-1] via strong N-H?I hydrogen
      bonds. The hydrogen-bonded chains are further packed in stacks along [100]. The
      thermal behaviour of I was studied by different physicochemical methods
      (thermogravimetry, differential scanning calorimetry and powder diffraction).
      Differential scanning calorimetry revealed three narrow endothermic peaks at 346,
      387 and 525 K, and one broad endothermic peak at ~605 K. The first and second
      peaks are related to solid-solid phase transitions, while the third and fourth
      peaks are attributed to the melting and decomposition of I. The enthalpies of the
      phase transitions at 346 and 387 K are estimated as 2.60 and 2.75 kJ mol-1,
      respectively. The X-ray powder diffraction data collected at different
      temperatures indicate the existence of I as the monoclinic (100-346 K), ortho
      rhom-bic (346-387 K) and cubic (387-525 K) polymorphic modifications.

PMID- 28435724
TI  - Crystal structures of two platinum(II) complexes containing ethyl eugenoxyacetate
      and 2-amino-pyridine.
AB  - In the title complexes, trans-(2-amino-pyridine-kappaN)di-chlorido-{4-eth-oxy
      carbonyl-meth-oxy-3-meth-oxy-1-[(2,3-eta)-prop-2-en-1-yl]benzene}-platinum(II),
      [PtCl2(C5H6N2)(C14H18O4)], (I), and (2-amino-pyridine-kappaN)chlorido{5-eth-oxy
      car-bon-yl-meth-oxy-4-meth-oxy-1-[(2,3-eta)-prop-2-en-1-yl]phenyl-kappaC1}
      platinum(II), [Pt(C14H17O4)Cl(C5H6N2)], (II), the central PtII metal atom
      displays a distorted square-planar coordination, with the PtII atom coordinated
      by the pyridine N atom, the C=C double bond of the eugenol ligand and two Cl
      atoms for (I) or one Cl atom and a C atom of the phenyl ring for (II). The allyl
      fragment in (I) is disordered, with population parameters 0.614 (14) and 0.386
      (14) for the two positions of the central C atom. The least-squares planes
      through the two aromatic ring systems make a dihedral angle of 51.10 (13) degrees
      for (I) and 78.5 (2) degrees  for (II). Intra-molecular N-H?O and N-H?pi inter
      actions occur in (I). In (I), inversion dimers formed by C-H?Cl inter-actions are
      further linked into chains parallel to the b axis by C-H?O hydrogen bonds. Both
      aromatic rings are involved in pi-pi inter-actions, with centroid-to-centroid
      distances of 3.508 (3) and 3.791 (3) A. In (II), inversion dimers form chains
      parallel to the b axis by C-H?O inter-actions.

PMID- 28435725
TI  - Hydrazinium 2-amino-4-nitro-benzoate dihydrate: crystal structure and Hirshfeld
      surface analysis.
AB  - In the anion of the title salt hydrate, H5N2+.C7H5N2O4-.2H2O, the carboxyl-ate
      and nitro groups lie out of the plane of the benzene ring to which they are bound
      [dihedral angles = 18.80 (10) and 8.04 (9) degrees , respectively], and as these
      groups are conrotatory, the dihedral angle between them is 26.73 (15) degrees .
      An intra-molecular amino-N-H?O(carboxyl-ate) hydrogen bond is noted. The main
      feature of the crystal packing is the formation of a supra-molecular chain along
      the b axis, with a zigzag topology, sustained by charge-assisted water-O
      H?O(carboxyl-ate) hydrogen bonds and comprising alternating twelve-membered
      {?OCO?HOH}2 and eight-membered {?O?HOH}2 synthons. Each ammonium-N-H atom forms a
      charge-assisted hydrogen bond to a water mol-ecule and, in addition, one of these
      forms a hydrogen bond with a nitro-O atom. The amine-N-H atoms form hydrogen
      bonds to carboxyl-ate-O and water-O atoms, and the amine N atom accepts a
      hydrogen bond from an amino-H atom. The hydrogen bonds lead to a three
      dimensional architecture. An analysis of the Hirshfeld surface highlights the
      major contribution of O?H/H?O hydrogen bonding to the overall surface, i.e.
      46.8%, compared with H?H contacts (32.4%).

PMID- 28435726
TI  - Crystal structure of 2-(aza-niumylmeth-yl)pyridinium bis(hydrogen squarate).
AB  - The asymmetric unit of the title compound, C6H10N22+.2C4HO4-, comprises two
      hydrogen squarate (Hsq-; systematic name: 2-hy-droxy-3,4-dioxo-cyclo-butano-late)
      anions and a 2-(aza-niumylmeth-yl)pyridinium dication. The squaric acid mol
      ecules each donate an H atom to the N atoms of the pyridine ring and the amino
      methyl units of a 2-(amino-meth-yl)pyridine mol-ecule, forming the 1:2 salt. The
      Hsq- anions are linked by strong O-H?O hydrogen bonds and an N-H?O hydrogen bond
      links the 2-(aza-niumylmeth-yl)pyridinium cation to one of the squaric acid
      anions. The crystal structure features additional N-H?O and O-H?O hydrogen bonds,
      pi-pi stacking and unusual weak C-O?pi(ring) inter-actions.

PMID- 28435727
TI  - Crystal structure of bis-(1,10-phenanthroline-kappa2N,N')(1,3-thia-zole-2-thiol
      ato-kappa2S2,N)nickel(II) hexa-fluorido-phosphate 1,4-dioxane sesquisolvate.
AB  - The title salt, [Ni(C3H2NS2)(C12H8N2)2]PF6.1.5C4H8O2, was the unexpected product
      on making an attempt to prepare an [Ni(2-mercapto-thia-zol-ate)(1,10
      phenanthroline)]+ complex by reaction of [NiCl2(1,10-phen-an-throline)] with 2
      mercapto-thia-zolate. In the resulting complex, the 2-mercapto-thia-zolate anion
      acts as a chelating ligand, which coordinates to the NiII ion with the thia-zolyl
      N and thiol-ate S atoms. In the crystal, pi-pi stacking inter-actions between the
      coordinating 1,10-phenanthroline mol-ecules of adjacent complexes result in a
      zigzag chain running parallel to the c axis. Weak C-H?X (X = O, F) hydrogen
      bonding inter-actions between the chains and 1,4-dioxane solvent mol-ecules and
      PF6- counter-anions lead to the formation of sheets parallel to the ac plane.

PMID- 28435728
TI  - Crystal structures of the Schiff base derivatives (E)-N'-[(1H-indol-3-yl)methyl
      idene]isonicotino-hydrazide ethanol monosolvate and (E)-N-methyl-2-[1-(2-oxo-2H
      chromen-3-yl)ethyl-idene]hydrazinecarbo-thio-amide.
AB  - The crystal structures of two title Schiff base derivatives, C15H12N4O.C2H6O
      (1.EtOH) and C13H13N3O2S (2), were determined at 110 and 100 K, respectively. In
      the crystal of compound 1.EtOH, the (E)-N'-[(1H-indol-3-yl)methyl
      idene]isonicotinohydrazide and ethanol mol-ecules are linked by O-H?O, N-H?O and
      N-H?N hydrogen bonds, forming a tape structure running along the b-axis
      direction. The tapes are weakly linked via a C-H?N inter-action. In the crystal
      of compound 2, (E)-N-methyl-2-[1-(2-oxo-2H-chromen-3-yl)ethyl
      idene]hydrazinecarbo-thio-amide mol-ecules are linked via N-H?O and C-H?O
      hydrogen bonds, forming a helical chain along the b-axis direction. The chains
      are further linked into a layer expanding parallel to (102) through C-H?S inter
      actions.

PMID- 28435729
TI  - Crystal structure of 4-nitro-phenyl 6-O-ethyl-beta-d-galacto-pyran-oside
      monohydrate.
AB  - The synthesis and crystal structure of the title compound, C14H19NO8.H2O,
      prepared in three steps from 6-O-ethyl-1,2;3,4-di-O-iso-propyl-idene-alpha-d
      galacto-pyran-ose using protecting-group strategies employed in carbohydrate
      chemistry, is reported. The asymmetric unit consists of a single galactoside mol
      ecule, in which the pyran-oid ring has a 4C1 conformation and the 4-nitro-phenyl
      moiety is essentially planar. In the crystal, each carbohydrate is surrounded by
      other d-galactose residues and water mol-ecules, linked by O-H?O hydrogen bonds
      involving all hy-droxy groups, giving a two-dimensional substructure lying
      parallel to (100) and extended into three dimensions by C-H?O inter-actions.

PMID- 28435730
TI  - Crystal structure of N-(2-benzoyl-5-ethynylphen-yl)quinoline-2-carboxamide.
AB  - In the title compound, C25H16N2O2, the quinoline ring system is essentially
      planar, with a maximum deviation of 0.030 (1) A, and forms a dihedral angle of
      20.9 (1) degrees  with benzoyl benzene ring. The unsubstituted phenyl ring forms
      dihedral angles of 52.7 (1) degrees  with the quinoline ring system and 54.1 (1)
      degrees  with the ethynyl-substituted benzene ring. The mol-ecule contains an
      intra-molecular bifurcated N-H?(O,N) hydrogen bond, forming S(5) and S(6) rings,
      which may influence the conformation of the mol-ecule. In the crystal, weak C-H?O
      hydrogen bonds link the mol-ecules into a three-dimensional network. In addition,
      the three-dimensional structure contains pi-pi stacking inter-actions, with
      centroid-centroid distances of 3.695 (1) and 3.751 (1) A.

PMID- 28435731
TI  - Crystal structure and absolute configuration of (4S,5R,6S)-4,5,6-trihy-droxy-3
      methyl-cyclo-hex-2-enone (gabosine H).
AB  - The mol-ecule of the title keto carbasugar, C7H10O4, is formed by a cyclo-hexene
      skeleton with an envelope conformation, substituted by carbonyl, methyl and
      hydroxyl groups. The crystal structure is controlled mainly by a combination of
      strong O-H?O and weak C-H?O hydrogen bonds, forming nearly perpendicular chains
      running parallel to the [110] and [-110] directions. This perpendicularity is
      caused by a tetra-gonal pseudosymmetry influenced by the similarity between the a
      and b axes, the value of 90.9770 (10) degrees  of the beta angle and the action
      of a 21 screw axis, which transform each chain into its corresponding nearly
      orthogonal one.

PMID- 28435733
TI  - Crystal structure of bis-(4-benzoyl-pyridine-kappaN)bis-(methanol-kappaO)bis
      (thio-cyanato-kappaN)cobalt(II).
AB  - The crystal structure of the title compound, [Co(NCS)2(C12H9NO)2(CH3OH)2],
      consists of cobalt(II) cations that are octa-hedrally coordinated by two N
      terminal bonding thio-cyanato anions, two methanol mol-ecules and two 4-benzoyl
      pyridine ligands into discrete complexes that are located on centres of
      inversion. These complexes are further linked by O-H?O hydrogen bonding between
      the hy-droxy H atom of the methanol ligand and the carbonyl O atom of the 4
      benzoyl-pyridine ligand of a neighboring complex into layers parallel to (101).
      No pronounced inter-molecular inter-actions are observed between these layers.

PMID- 28435732
TI  - Crystal structures of three 4-substituted-2,2'-bipyridines synthesized by
      Sonogashira and Suzuki-Miyaura cross-coupling reactions.
AB  - Facile synthetic routes for three 4-substituted 2,2'-bi-pyridine derivatives, 4
      [2-(4-methyl-phenyl)-ethyn-yl]-2,2'-bi-pyridine, C19H14N2, (I), 4-[2-(pyridin-3
      yl)ethyn-yl]-2,2'-bi-pyridine, C17H11N3, (II), and 4-(indol-4-yl)-2,2'-bi
      pyridine, C18H13N3, (III), via Sonogashira and Suzuki-Miyaura cross-coupling
      reactions, respect-ively, are described. As indicated by X-ray analysis, the 2,2'
      bi-pyridine core, the ethyl-ene linkage and the substituents of (I) and (II) are
      almost planar [dihedral angles between the two ring systems: 8.98 (5) and 9.90
      (6) degrees  for the two mol-ecules of (I) in the asymmetric unit and 2.66 (14)
      degrees  for (II)], allowing pi-conjugation. On the contrary, in (III), the
      indole substituent ring is rotated significantly out of the bi-pyridine plane
      [dihedral angle = 55.82 (3) degrees ], due to steric hindrance. The crystal
      packings of (I) and (II) are dominated by pi-pi inter-actions, resulting in
      layers of mol-ecules parallel to (30-2) in (I) and columns of mol-ecules along
      the a axis in (II). The packing of (III) exhibits zigzag chains of mol-ecules
      along the c axis inter-acting through N-H?N hydrogen bonds and pi-pi inter
      actions. The contributions of unknown disordered solvent mol-ecules to the
      diffraction intensities in (II) were removed with the SQUEEZE [Spek (2015 ?).
      Acta Cryst. C71, 9-18] algorithm of PLATON. The given chemical formula and other
      crystal data do not take into account these solvent mol-ecules.

PMID- 28435734
TI  - Crystal structure of tetra-aqua-bis-(pyrimidin-1-ium-4,6-diolato
      kappaO4)manganese(II).
AB  - The MnII ion in the structure of the mononuclear title compound,
      [Mn(C4H3N2O2)2(H2O)4], is situated on an inversion center and is coordinated by
      two O atoms from two deprotonated 4,6-di-hydroxy-pyrimidine ligands and by four O
      atoms from water mol-ecules giving rise to a slightly distorted octa-hedral
      coordination sphere. The complex includes an intra-molecular hydrogen bond
      between an aqua ligand and the non-protonated N ring atom. The extended structure
      is stabilized by inter-molecular hydrogen bonds between aqua ligands, by hydrogen
      bonds between N and O atoms of the ligands of adjacent mol-ecules, and by
      hydrogen bonds between aqua ligands and the non-coordinating O atom of an
      adjacent mol-ecule.

PMID- 28435735
TI  - Crystal structure and Hirshfeld surface analysis of 1-(4-bromo-phen-yl)-2-{[5
      (pyridin-3-yl)-1,3,4-oxa-diazol-2-yl]sulfan-yl}ethan-1-one.
AB  - In the title compound, C15H10BrN3O2S, the dihedral angles between the 1,3,4-oxa
      diazole ring and the 3-pyridinyl and bromo-benzene rings are 12.17 (15) and 18.74
      (15) degrees , respectively. In the crystal, the mol-ecules are linked into [100]
      chains by way of C-H?O, C-H?N, C-H?S hydrogen bonds. The Hirshfeld surface
      analysis indicates that the most important contributions to the packing are H?H
      (19.5%), N?H (17.3%), C?H (15.5%), Br?H (11.7%), and O?H (11.0%) inter-actions.

PMID- 28435736
TI  - Crystal structure of 1,3-bis-[(E)-benzyl-idene-amino]-propan-2-ol.
AB  - In the title compound, C17H18N2O, the central carbon atom with the OH substituent
      and one of the (E)-benzyl-idene-amino substituents are disordered over two sets
      of sites with occupancies of 0.851 (4) and 0.149 (4). The relative positions of
      the two disorder components is equivalent to a rotation of approximately 60
      degrees  about the C-N single bond. In the crystal, the mol-ecules are held
      together by O-H?N hydrogen bonds, forming simple C(5) chains along the b-axis
      direction. In addition, pairs of the chains are further aggregated by weak C-H?pi
      inter-actions.

PMID- 28435737
TI  - N'-[1-(5-Bromo-2-hy-droxy-phen-yl)ethyl-idene]isonicotinohydrazide monohydrate:
      crystal structure and Hirshfeld surface analysis.
AB  - In the title isonicotinohydrazide hydrate, C14H12BrN3O2.H2O {systematic name: N'
      [(1E)-1-(5-bromo-2-hy-droxy-phen-yl)ethyl-idene]pyridine-4-carbohydrazide
      monohydrate}, the central CN2O region of the organic mol-ecule is planar and the
      conformation about the imine-C=N bond is E. While an intra-molecular hy-droxy-O
      H?N(imine) hydrogen bond is evident, the dihedral angle between the central
      residue and the benzene rings is 48.99 (9) degrees . Overall, the mol-ecule is
      twisted, as seen in the dihedral angle of 71.79 (6) degrees  between the outer
      rings. In the crystal, hydrogen-bonding inter-actions, i.e. hydrazide-N
      H?O(water), water-O-H?O(carbon-yl) and water-O-H?N(pyrid-yl), lead to supra
      molecular ribbons along the a-axis direction. Connections between these, leading
      to a three-dimensional architecture, are mediated by Br?Br halogen bonding
      [3.5366 (3) A], pyridyl-C-H?O(carbon-yl) as well as weak pi-pi inter-actions
      [inter-centroid separation between benzene rings = 3.9315 (12) A]. The Hirshfeld
      surface analysis reveals the importance of hydrogen atoms in the supra-molecular
      connectivity as well as the influence of the Br?Br halogen bonding.

PMID- 28435738
TI  - Crystal structure of [2-({2-[(2-azanidyl-benzyl-idene)amino]-benzyl-idene}amino)
      4-chloro-phenol-ato]nickel(II).
AB  - The title complex, [Ni(C20H14ClN3O)], with an asymmetrically chloride-appended
      Schiff base ligand has been synthesized and structurally characterized at 100 K.
      In the compound, the central nickel(II) ion has a square-planar coordination
      geometry with N3O donors of the pi-conjugated tetra-dentate Schiff base ligand.
      In the crystal, the complexes are connected into an inversion dimer via an Ni?Ni
      inter-action [3.1753 (5) A] and a pair of pi-pi inter-actions [centroid-centroid
      distance = 3.8416 (16) A]. The dimers are linked via a C-H?Cl hydrogen bond,
      forming a chain along the c-axis direction. The dimer chains inter-act with each
      other through pi-pi inter-actions [centroid-centroid distance = 3.8736 (16) A],
      forming a layer expanding parallel to the ac plane.

PMID- 28435739
TI  - Crystal structure of [Cu(tmpen)](BF4)2 {tmpen is N,N,N',N'-tetra-kis-[(6-methyl
      pyridin-2-yl)meth-yl]ethane-1,2-di-amine}.
AB  - The mononuclear copper title complex {N,N,N',N'-tetra-kis-[(6-methyl-pyridin-2
      yl)meth-yl]ethane-1,2-di-amine-kappa6N}copper(II) bis-(tetra-fluorido-borate),
      [Cu(C30H36N6)](BF4)2, is conveniently prepared from the reaction of Cu(BF4)2.6H2O
      with N,N,N',N'-tetra-kis-[(6-methyl-pyridin-2-yl)meth-yl]ethane-1,2-di-amine
      (tmpen) in aceto-nitrile at room temperature in air. The complex shows a
      distorted octa-hedral environment around the CuII cation (site symmetry 2) and
      adopts the centrosymmetric space group C2/c. The presence of the 6-methyl
      substituent hinders the approach of the pyridine group to the CuII core. The bond
      lengths about the CuII atom are significantly longer than those of analogues
      without the 6-methyl substituents.

PMID- 28435740
TI  - Crystal structure of 3,3'-biisoxazole-5,5'-bis(methyl-ene) dinitrate (BIDN).
AB  - The mol-ecular structure of the title energetic compound, C8H6N4O8, is composed
      of two planar isoxazole rings and two near planar alkyl-nitrate groups (r.m.s
      deviation = 0.006 A). In the crystal, the mol-ecule sits on an inversion center,
      thus Z' = 0.5. The dihedral angle between the isoxazole ring and the nitrate
      group is 69.58 (8) degrees . van der Waals contacts dominate the inter-molecular
      inter-actions. Inversion-related rings are in close slip-stacked proximity, with
      an inter-planar separation of 3.101 (3) A [centroid-centroid distance = 3.701 (3)
      A]. The measured and calculated densities are in good agreement (1.585 versus
      1.610 Mg m-3).

PMID- 28435741
TI  - The influence of clarification and threats on life situation: patients'
      experiences 1 year after TSCI.
AB  - INTRODUCTION: The study was conducted at the Spinal Cord Injury Centre of Western
      Denmark (VCR). The aim of the study was to explore patients' experiences
      following traumatic spinal cord injury and to identify characteristics of
      positive versus negative life situation 1 year post discharge from hospital
      rehabilitation. This was a qualitative study conducted using inductive content
      analysis. CASE PRESENTATION: In this qualitative study seven patients were
      interviewed one year after discharge from initial rehabilitation at the VCR. The
      interviews were analysed using inductive content analysis. DISCUSSION: We found
      that two categories condensed the patients' experiences of their life situation 1
      year post discharge: 'clarification in relation to overall life situation' and
      'threat to core competences'. The transversal analysis across the derived
      categories identified different combinations of clarification and threats to core
      competences explaining the patients' experiences: high degree of clarification
      combined with low degree of threat to core competences was indicative of positive
      life situation. Also, positive life situation was seen when a high degree of
      clarification compensated for high degree of threats on core competencies. In
      contrast, an overall stressful and negative life situation was influenced by poor
      clarification combined with a high degree of threat to core competences. However,
      when core competences can be transformed into new skills, threats were
      manageable. This study revealed that clarification related to overall life
      situation in combination with threat to core competences may explain traumatic
      spinal cord injury patients' overall life situation 1 year post discharge. An
      appropriate balance characterises a positive life situation. There might be a
      need to pay attention to patients who are challenged by low degree of
      clarification and high degree of threats on core competencies 1 year post
      discharge as this may influence the life situation negatively.

PMID- 28435742
TI  - Immobilisation-induced hypercalcemia following spinal cord injury affecting the
      kidney function in two young native Greenlanders.
AB  - INTRODUCTION: Immobilisation-induced hypercalcemia following SCI affecting the
      kidney function, is a rare but potentially serious condition. We report
      immobilisation-induced hypercalcemia affecting the kidney function in two young
      native Greenlanders with spinal cord injury (SCI). CASE PRESENTATIONS: Two 15-
      and 24-year-old male native Greenlanders, both with traumatic C5 SCI were
      admitted to our spinal cord unit. They were non-smokers without history of daily
      alcohol intake pre- or immediately post-injury. No physical demanding activities
      pre-injury. Due to complaints of nausea/vomiting 10-12 weeks post-injury, not
      explained by usual causes such as urinary tract infection, blood samples were
      drawn and hypercalcaemia found. Both patients started treatment including
      increased hydration. Within 1 month calcium ion, plasma-creatinine and plasma
      carbamide were normalised. DISCUSSION: Over the last 20 years our spinal cord
      unit has only experienced immobilisation-induced hypercalcemia following SCI
      affecting the kidney function in two young male native Greenlanders. This finding
      of immobilisation-induced hypercalcemia following SCI affecting the kidney
      function in two young native Greenlanders, but not in the rest of our primary
      native Danish patient population, also including youngsters, suggests that
      ethnicity may be a pre-disposing factor.

PMID- 28435743
TI  - Effects of overground locomotor training on the ventilatory response to
      volitional treadmill walking in individuals with incomplete spinal cord injury: a
      pilot study.
AB  - INTRODUCTION: Although there has been substantial emphasis on the neuromuscular
      and cardiovascular adaptations following rehabilitation, pulmonary adaptations in
      individuals with incomplete SCI (iSCI) in response to locomotor training have
      been less frequently studied. In healthy individuals, effective transition from
      rest to work is accomplished by a hyperpneic response, which exhibits an
      exponential curve with three phases. However, the degree to which our current
      understanding of exercise hyperpnea can be applied to individuals with iSCI is
      unknown. The purpose of this case series was to characterize exercise hyperpnea
      during a rest to constant work rate (CWR) transition before and after 12-15 weeks
      of overground locomotor training (OLT). CASE PRESENTATION: Six subjects with
      cervical motor incomplete spinal cord injury participated in 12-15 weeks of OLT.
      Subjects were trained in 90-min sessions twice a week. All training activities
      were weight-bearing and under volitional control without the assistance of body
      weight support harnesses, robotic devices or electrical stimulation. Six minutes
      of CWR treadmill walking was performed at self-selected pace with
      cardiorespiratory analysis throughout the tests before and after OLT. Averaged
      group data for tidal volume, breathing frequency or VE showed no difference
      before and after training. VE variability was decreased by 46.7% after OLT.
      DISCUSSION: CWR VE from rest to work was linear throughout the transition.
      Following OLT, there was a substantial reduction in VE variability. Future
      research should investigate the lack of a phasic ventilatory response to
      exercise, as well as potential mechanisms of ventilatory variability and its
      implications for functional performance.

PMID- 28435744
TI  - Diagnosis of spinal epidural abscess: a case report and literature review.
AB  - INTRODUCTION: Spinal epidural abscess (SEA) is a rare but serious cause of back
      pain in the critical care setting. It occurs most commonly in adults in their
      fifth and sixth decades of life. Risk factors include diabetes mellitus,
      alcoholism, AIDS or other immunocompromised states, cancer, intravenous drug use,
      trauma and spinal surgery. The clinical presentation can be non-specific but the
      classical triad includes back pain, fever and neurological deficits. Magnetic
      resonance imaging (MRI) with gadolinium is the diagnostic imaging modality of
      choice. CASE PRESENTATION: Here we report a case of SEA in a 63-year-old man with
      type II diabetes who presented with severe low back pain. He was found to have
      SEA likely secondary to a hip joint injection. The diagnosis was delayed due an
      earlier non-gadolinium-enhanced MRI of the spine showing no epidural abscess.
      DISCUSSION: This case stresses the need for the definitive diagnostic study, MRI
      with gadolinium, in patients whose SEA is high on the list of differential
      diagnoses.

PMID- 28435745
TI  - A Consult Service to Support and Promote Community-Based Research: Tracking and
      Evaluating a Community-based Research Consult Service.
AB  - PURPOSE: This study describes the design, operation and evaluation of a community
      based research (CBR) consult service within the setting of a Clinical and
      Translational Science Award (CTSA) institution. To our knowledge, there are no
      published evaluations of a CBR consult service at a CTSA hub. METHODS: A
      community-based research Consult Service was created to support faculty, health
      care providers/research coordinators, trainees, community-based organizations and
      community members. A framework was developed to assess the stages of client
      engagement and to foster clear articulation of client needs and challenges. A
      developmental evaluation system was integrated with the framework to track
      progress, store documents, continuously improve the consult service and assess
      research outcomes. RESULTS: This framework provides information on client
      numbers, types, services used and successful outreach methods. Tracking progress
      reveals reasons that prevent clients from completing projects and facilitates
      learning outcomes relevant to clients and funding agencies. Clients benefit from
      the expert knowledge, community connections and project guidance provided by the
      Consult Service team, increasing the likelihood of study completion and achieving
      research outcomes. CONCLUSION: This study offers a framework by which CTSA
      institutions can expand their capacity to conduct and evaluate community-based
      research while addressing challenges that inhibit community engagement.

PMID- 28435746
TI  - The paradoxical functions of EGFR during breast cancer progression.
AB  - The epidermal growth factor receptor (EGFR) is one of the most well-studied
      signaling pathways in cancer progression. As a result, numerous therapeutics
      including small-molecule inhibitors and monoclonal antibodies have been developed
      to target this critical oncogenic driver. Several of these EGFR inhibitors
      (EGFRi) have been evaluated in metastatic breast cancer, as high-level EGFR
      expression in primary tumors correlates with the highly aggressive basal-like
      phenotype and predicts for poor patient prognosis. Surprisingly, these trials
      have been unanimously unsuccessful at improving patient outcomes. Numerous
      factors, such as lack of proper patient selection may have contributed to the
      failure of these trials. However, recent findings suggest that there are
      fundamental changes in EGFR signaling that take place during primary tumor
      invasion, dissemination and ultimate metastasis of breast cancer cells. Herein,
      we review the outcomes of EGFR-targeted clinical trials in breast cancer and
      explore our current understanding of EGFR signaling within primary mammary tumors
      and how these events are altered in the metastatic setting. Overall, we put forth
      the hypothesis that fundamental changes in EGFR signaling between primary and
      metastatic tumors, a process we term the 'EGFR paradox,' contribute to the
      clinically observed inherent resistance to EGFRi. Furthermore, this hypothesis
      introduces the possibility of utilizing EGFR agonism as a potential therapeutic
      approach for the treatment of metastatic breast cancer.

PMID- 28435747
TI  - Determination of the Health Belief and Attitude of Women Regarding Breast Cancer
      and Breast Self-Exam.
AB  - OBJECTIVE: This study has been carried out with the purpose of determining the
      belief and attitude of women regarding breast cancer and breast self-exam and the
      factors which affect the performance frequency of breast self-exam and it is a
      descriptive kind of study. MATERIALS AND METHODS: Data has been collected through
      questionnaire forms created by the researchers based on literature information
      and Champion Health Belief Model Scale. Data collection was collected via face-to
      face interviews with the patients. Questionnaire forms were applied to 350 women
      who accepted to participate in the study. Data was analyzed frequency,
      percentage, t-test and x2 test with SPSS for Windows 12.0. RESULTS: Average age
      of women who were included in the study was found to be 33.25+/-10.27. Average
      point for the sensitivity sub-dimension of the women within the scope of study
      was 7.79+/-2.38, average score for the seriousness sub-dimension 23.30+/-5.82,
      average score for the benefit sub-dimension 15.48+/-4.03, average score for the
      obstacle sub-dimension was 26.34+/-7.64, average score of health motivation sub
      dimension was 32.77+/-9.11 and average score for the self-confidence sub
      dimension was 25.20+/-5.02. CONCLUSION: The beliefs of women regarding the
      subject should be developed by providing in-service training regarding breast
      cancer and breast self-exam. It can be suggested that studies be carried out
      analyzing the effect of the attempts for increasing the performance frequency of
      breast self-exam of women on the beliefs and attitudes.

PMID- 28435748
TI  - Extracellular Vesicles: Evolving Contributors in Autoimmunity.
AB  - Extracellular vesicles, including microvesicles, exosomes and apoptotic bodies
      are recognized as carriers of pathogen-associated molecules with direct
      involvement in immune signaling and inflammation. Those observations have
      enforced the way these membranous vesicles are being considered as promising
      immunotherapeutic targets. In this review, we discuss the emerging roles of
      extracellular vesicles in autoimmunity and highlights their potential use as
      disease biomarkers as well as targets for the treatment and prevention of
      autoimmune diseases.

PMID- 28435750
TI  - Guest Editors' Message: Hawai'i's Healthcare Workforce.

PMID- 28435749
TI  - Rh(III)-Catalyzed Aryl and Alkenyl C-H Bond Addition to Diverse Nitroalkenes.
AB  - The transition metal catalyzed C-H bond addition to nitroalkenes has been
      developed. Very broad nitroalkene scope was observed for this Rh(III)-catalyzed
      method, including for aliphatic, aromatic and beta,beta-disubstituted
      derivatives. Additionally, various directing groups and both aromatic and alkenyl
      C-H bonds were effective in this transformation. Representative nitroalkane
      products were converted to dihydroisoquinolones and dihydropyridones in a single
      step and in high yield by iron mediated reduction and in situ cyclization.
      Moreover, preliminary success in enantioselective Rh(III)-catalyzed C-H bond
      addition to nitroalkenes was achieved as was X-ray structural characterization of
      a nitronate intermediate.

PMID- 28435751
TI  - Hawai'i Physician Workforce Assessment 2016: Improvement in Physician Numbers but
      Physician Suicides of Concern.
AB  - Hawai'i's Physician Workforce Assessment project was launched in 2010. Over the
      past 5 years the State has experienced decreases and increases in physician
      workforce. This current article describes the status of the physician workforce,
      past trends and anticipated projections as well as recent insights into why
      people leave Hawai'i. Survey data, internet searches and direct dialing
      methodologies were utilized to clarify and elucidate practice location, full time
      equivalency of time providing patient care and specialty of non-military
      physicians caring for Hawai'i's population. A proprietary microsimulation
      modeling methodology from the company the US Health Resources and Services
      Administration employs is utilized to assess demand. The current shortage of
      physicians is estimated to be between 455 and 707 full time equivalents with the
      greatest percentage of shortages on neighbor islands. Numerically the greatest
      total shortage of physicians is on O'ahu and the specialty in greatest demand is
      primary care with a shortage of 228 Full Time Equivalents (FTEs). Physician
      average age in Hawai'i is 54.9 compared to a national average of 51. There was an
      increase in the number of physicians who report using telehealth, from 2% to 15%.
      Initial improvements in the size of Hawai'i's physician workforce are promising,
      but we note two reported suicides in the intervening year. More attention must be
      paid to support practicing physicians in addition to our efforts to recruit new
      physicians.

PMID- 28435752
TI  - Preliminary Hawai'i Public Health Workforce Supply and Demand Assessment.
AB  - Ensuring the adequacy of the public health workforce requires an understanding of
      its size and composition, as well as the population's demand for services. The
      current article describes research undertaken as a first step toward developing
      an estimate of the supply of and demand for Hawai'i's public health workforce.
      Using an organizational-level survey, data was obtained from a subset of 34
      organizations considered to be major providers of population-based public health
      services in Hawai'i. The results indicate that estimates of the existing public
      health workforce range from 3,429 to 3,846 workers. Calculations of functional
      demand reveal that an additional 317 to 502 employees will be required to
      compensate for vacancies and projected retirements over the next five years;
      though, the discussion points to the fact that this number may be closer to 1,005
      to 1,664. While, an additional 594 to 848 employees would be needed to meet the
      current missions of organizations in this sample and to best meet community need.
      While these findings are neither exhaustive nor definitive, they raise issues
      concerning the state's supply of public health workers in terms of their ability
      to adequately meet demand for services. More research is needed to confirm these
      findings and track Hawai'i's public health workforce to assure a strong local
      public health system.

PMID- 28435753
TI  - Does Hawai'i Have Enough Psychiatrists? Assessing Mental Health Workforce Versus
      Demand in the Aloha State.
AB  - National data reports the number of adults with any diagnosable mental disorder
      within a given year is nearly 1 in 5. Hawai'i, along with the rest of the nation,
      faces a serious shortage of mental health providers. This article describes the
      research undertaken to create a more accurate assessment of the current mental
      health provider workforce in Hawai'i through developing an estimation strategy to
      appraise local mental health workforce needs. The results indicate the supply of
      psychiatrists for Hawai'i's 2010 census population was found to be 161.4 Full
      Time Equivalents (FTEs) psychiatrists, or 11.86 psychiatrists/100,000 population,
      with the greatest number of psychiatrists per capita on the island of O'ahu. Of
      the 161.4 FTEs, 50.4 FTEs or 31.2% were accepting new Medicaid patients. The
      state's results show that Hawai'i is short of meeting current patient need by
      more than 100 psychiatrists though the state was only short by 6 FTE
      psychiatrists with regard to estimates of Medicaid patients' need. While the
      first number is likely accurate, the second number is likely to be significantly
      underestimated for a number of reasons. One reason is that practitioners who
      reported accepting new Medicaid patients likely see comparatively few. Another
      reason is that it is likely that Medicaid patients make up more than the
      approximate 20% of the psychiatric patient population. It is reported nationally
      that a greater percentage of the mentally ill receive Medicaid than the
      population at large. Thus, there are probably many more patients on Medicaid than
      our estimations accounted for. It is clear more research and more changes need to
      be made in Hawai'i's publicly funded healthcare system to incentivize physician
      acceptance and make mental healthcare more accessible to this growing population.

PMID- 28435754
TI  - Establishing Successful Patient-Centered Medical Homes in Rural Hawai'i: Three
      Strategies to Consider.
AB  - The challenges to healthcare delivery posed by Hawai'i's unique geography,
      physician shortages, and dispersed population are of particular importance in
      light of implementing the Affordable Care Act (ACA). This study draws on central
      goals laid out in the ACA - to decrease costs, increase access, and improve
      patient outcomes. The use of the Patient-Centered Medical Homes (PCMHs) is a care
      model that has the potential to meet all three goals. How to identify the most
      effective way to develop PCMHs in the specific context of Hawai'i is the focus of
      this study. To provide recommendations for effective PCMH formation, a
      qualitative review of previously compiled data from the Hawai'i/Pacific Basin
      Area Health Education Center (AHEC) and phone interviews with six primary care
      providers throughout the islands were conducted. The results broadly suggest
      three paths towards the effective implementation of PCMHs in Hawai'i. The first
      recommendation is to create a PCMH template or business model for physicians in
      order to ease the complexities of implementing such an elaborate system of care.
      The second two recommendations actually veer away from PCMH towards general
      interventions to increase care in rural Hawai'i. Thus, the second recommendation
      is to create a specific track for becoming a rural practitioner at the John A.
      Burns School of Medicine (JABSOM) to increase the retention of physicians in
      underserved areas. And the final recommendation is to increase utilization of
      telemedicine techniques to overcome physician shortages and geographic challenges
      by allowing rural physicians to network with specialists on neighbor islands.
      These three strategies are all possible to accomplish with commitment and could
      be implemented to benefit the providers and rural population of Hawai'i.

PMID- 28435755
TI  - Comparison of Primary Care Physician Reimbursement Rates in the United States.
AB  - With a growing shortage of physicians, particularly primary care physicians, the
      issue of adequate pay in Hawai'i is increasingly important. Anecdotal reports of
      low pay in Hawai'i have rarely been substantiated. Data from FAIR Health, a
      company that tracks private insurance reimbursement rates, is compared across the
      United States (US) for the CPT code 99213. In addition, FAIR Health and Medicare
      rates are compared for cities with both similar and disparate cost of living to
      Hawai'i. Hawai'i is in the second lowest quintile for payment in the US for
      private insurances, and providers are reimbursed significantly lower than in
      cities with similar cost of living by both Medicare and private insurances.
      Methods for increasing payment to physicians in Hawai'i are essential to
      recruiting the necessary workforce. Revising payment methodologies that increase
      pay for services in areas of unmet need, revising Medicare Geographic Price Cost
      Indices to better balance pay in areas of need, and making use of the 10%
      Medicare Bonus Program for physicians working in Health Professions Shortage
      Areas are first steps to creating a sustainable plan for physician payment in the
      future.

PMID- 28435756
TI  - Identifying Barriers in the Use of Electronic Health Records in Hawai'i.
AB  - Hawai'i faces unique challenges to Electronic Health Record (EHR) adoption due to
      physician shortages, a widespread distribution of Medically Underserved Areas and
      Populations (MUA/P), and a higher percentage of small independent practices.
      However, research on EHR adoption in Hawai'i is limited. To address this gap,
      this article examines the current state of EHR in Hawai'i, the barriers to
      adoption, and the future of Health Information Technology (HIT) initiatives to
      improve the health of Hawai'i's people. Eight focus groups were conducted on
      Lana'i, Maui, Hawai'i Island, Kaua'i, Moloka'i, and O'ahu. In these groups, a
      total of 51 diverse health professionals were asked about the functionality of
      EHR systems, barriers to use, facilitators of use, and what EHRs would look like
      in a perfect world. Responses were summarized and analyzed based on constant
      comparative analysis techniques. Responses were then clustered into thirteen
      themes: system compatibility, loss of productivity, poor interface, IT support,
      hardware/software, patient factors, education/training, noise in the system,
      safety, data quality concerns, quality metrics, workflow, and malpractice
      concerns. Results show that every group mentioned system compatibility. In
      response to these findings, the Health eNet Community Health Record initiative -
      which allows providers web-based access to patient health information from the
      patient's provider network- was developed as a step toward alleviating some of
      the barriers to sharing information between different EHRs. The Medicare Access
      and CHIP Reauthorization Act of 2015 (MACRA) legislation will introduce a new
      payment model in 2017 that is partially based on EHR utilization. Therefore, more
      research should be done to understand EHR adoption and how this ruling will
      affect providers in Hawai'i.

PMID- 28435757
TI  - Beyond the Ability to Pay: The Health Status of Native Hawaiians and Other
      Pacific Islanders in Relationship to Health Insurance.
AB  - Native Hawaiians and Other Pacific Islanders (NHOPI) suffer from a number of poor
      health outcomes, such as high rates of overweight status, obesity, hypertension,
      and high rates of asthma and cancer mortality. In addition to a disproportionate
      burden of illness, barriers to health care access and utilization also exist.
      This study examines the effect of health insurance coverage on the health status
      of NHOPI in comparison to Asians. To analyze this relationship, the study uses
      the Behavioral Risk Factor Surveillance System (BRFSS) 2012 data and logistic
      regression. Findings show insured NHOPI were significantly more likely than
      insured Asian Americans to report poor or fair health after sequential cumulative
      adjustments of socioeconomic, lifestyle and behavioral factors, history of
      diagnosed diseases, and access to care (OR: 1.66, 95% CI:[1.34, 2.05]). Health
      insurance alone will not eliminate the present disparities experienced by NHOPI.
      Other barriers prohibit health care access for NHOPI that should be considered in
      the investigation and development of strategies to increase healthcare access and
      eliminate health disparities for NHOPI.

PMID- 28435758
TI  - Obamacare: A View From the Outside.

PMID- 28435759
TI  - MD 5 Big Island Adventures: The Challenges and Rewards of Rural Physician
      Practices.

PMID- 28435760
TI  - Important Factors To Consider When Developing Rural Healthcare Systems:
      Suggestions From A Moloka'i Native.

PMID- 28435762
TI  - Laboratory Diagnosis of Scabies Using a Simple Saline Mount: A Clinical
      Microbiologist's Report.
AB  - Scabies is a skin condition caused by infestation of the mite Sarcoptes scabiei.
      Sarcoptes scabiei var. hominis is an arthropod member belonging to the order
      Acarina. Scabies is present throughout the world and is prevalent in all age
      groups, mostly involving people frequently in contact with animals, children,
      women, and elderly people. Predisposing factors for scabies include individuals
      with immunosuppressive conditions and people residing under low socioeconomic
      conditions. Skin lesions that occur during mite infestation closely resemble
      dermatological disorders caused by microbes, including fungi, parasites, and
      viruses. Laboratory diagnosis of scabies greatly relies on an accurate clinical
      suspicion and the demonstration of mites in the skin scrapings could be used for
      confirmation. It should be noted that a greater understanding between a clinician
      or a dermatologist and a clinical microbiologist is required to successfully
      diagnose scabies. This report details an easily performed, cost-effective method,
      the simple saline mount, that a clinical microbiology laboratory should follow to
      successfully identify mites in skin scrapings.

PMID- 28435761
TI  - Dual-Energy CT in Head and Neck Imaging.
AB  - PURPOSE OF REVIEW: To explain the technique of Dual-energy CT (DECT) and
      highlight its applications and advantages in head and neck radiology. RECENT
      FINDINGS: Using DECT, additional datasets can be created next to conventional
      images. In head and neck radiology, three material decomposition algorithms can
      be used for improved lesion detection and delineation of the tumor. Iodine
      concentration measurements can aid in differentiating malignant from nonmalignant
      lymph nodes and benign posttreatment changes from tumor recurrence. Virtual non
      calcium images can be used for detection of bone marrow edema. Virtual mono
      energetic imaging can be useful for improved iodine conspicuity at lower keV and
      for reduction of metallic artifacts and increase in signal-to-noise ratio at
      higher keV. SUMMARY: DECT and its additional reconstructions can play an
      important role in head and neck cancer patients, from initial diagnosis and
      staging, to therapy planning, evaluation of treatment response and follow-up.
      Moreover, it can be helpful in imaging of infections and inflammation and
      parathyroid imaging as supplementary reconstructions can be obtained at lower or
      equal radiation dose compared with conventional single energy scanning.

PMID- 28435763
TI  - Toxoplasma Infection in an Immunocompetent Host: Possible Risk of Living with
      Multiple Cats.
AB  - A 32-year-old man presented with agitation, headache, and confusion. He was
      immunocompetent and had been living with multiple cats for many years. His vital
      signs were stable. He was afebrile. Multiple blood tests did not show any serious
      problem. Brain magnetic resonance imaging (MRI) revealed multiple ring-enhancing
      white matter lesions. Cerebrospinal fluid analysis did not show any signs of
      infection. Based on a presumptive diagnosis of multiple sclerosis, high-dose
      corticosteroid treatment was started. However, this caused worsening of the
      symptoms and increased the size of the lesions. Corticosteroids were discontinued
      and biopsy was done. Biopsy of the lesions confirmed Toxoplasma gondii infection,
      and treatment with pyrimethamine/sulfadiazine was initiated. Treatment decreased
      the size of the lesions dramatically. Toxoplasma infection of the central nervous
      system (CNS) is rare in immunocompetent hosts. Living with multiple cats is
      believed to be a risk factor for Toxoplasma infection in immunocompetent hosts.

PMID- 28435764
TI  - A Case of Well-Differentiated Papillary Mesothelioma of the Male Peritoneum:
      Successful Treatment by Systemic Chemotherapy.
AB  - Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare
      subtype of epithelioid mesothelioma, which is usually seen in young women without
      a history of asbestos exposure, and generally, has an indolent course. The
      relative rarity of this neoplasm in males prompted us to report this case of a
      well-differentiated papillary mesothelioma of the peritoneum in a 36-year-old
      man. The patient, who had no history of asbestos exposure, presented with
      abdominal pain and ascites of unknown etiology. Computed tomography showed
      abundant ascites with nodules of the peritoneal cavity. Laparoscopic examination
      revealed a large number of white miliary nodules diffusely covering the
      peritoneum. Pathology revealed a diagnosis of well-differentiated papillary
      mesothelioma of the peritoneum, based on histomorphology and
      immunohistochemistry. The patient started chemotherapy with cisplatin and
      pemetrexed. After six cycles of chemotherapy, the effectiveness of this
      chemotherapy was checked by only the computed tomography. PET scan was not used
      because it is not routinely recommended in WDPMP. Few data are currently
      available in the literature regarding the performance of the PET scan in WDPMP.
      Nine months later, the patient was free of symptoms. Based on reviewing the
      literature and our observations in this case, consultation of other pathologists
      is highly recommended to discern WDPMP from other disseminated peritoneal
      diseases, in order to offer the most effective and safe therapeutic strategy.
      Chemotherapy should be strongly considered if the tumor is unresectable and
      accompanied by symptoms. Cisplatin and pemetrexed chemotherapy could be a
      promising therapeutic choice.

PMID- 28435765
TI  - Chronic Nephropathy from Dietary Hyperoxaluria: Sustained Improvement of Renal
      Function after Dietary Intervention.
AB  - A 56-year-old man with stable chronic kidney disease (CKD) for two years
      following a single episode of calcium oxalate urolithiasis developed progressive
      elevation of his serum creatinine concentration. Urinalysis revealed pyuria and
      white cell casts, a few red blood cells, minimal proteinuria, and no crystals.
      Urine culture was sterile. Gallium scintigraphy was consistent with interstitial
      nephritis. Proton pump inhibitor intake was discontinued, and a short course of
      oral corticosteroids was initiated. Percutaneous kidney biopsy, performed because
      of the continued deterioration of renal function to a minimum estimated
      glomerular filtration rate (eGFR) value of 15 mL/min per 1.73 m2 and persistent
      pyuria, revealed deposition of oxalate crystals in the tubules and interstitium,
      pronounced tubular changes, and interstitial nephritis and fibrosis. Urinary
      oxalate excretion was very high, in the range usually associated with primary
      hyperoxaluria. However, investigations for primary or enteric hyperoxaluria were
      negative. He reported a diet based on various nuts high in oxalate content.
      Estimated oxalate content in the diet was, for years, approximately four times
      higher than that in the average American diet. The institution of a diet low in
      oxalates resulted in the rapid normalization of urinary oxalate excretion and
      urinary sediment and in the slow, continuous improvement of renal function to
      near normal levels (eGFR 59 mL/min/1.73 m2) before his death from a brain
      malignancy 3.5 years later. The manifestations of nephropathy secondary to
      dietary hyperoxaluria, including the urine findings, can be indistinguishable
      from other types of interstitial nephritis. The diagnosis of dietary
      hyperoxaluria requires careful dietary history and a kidney biopsy. Identifying
      dietary hyperoxaluria as the cause of CKD is important because the decrease in
      dietary oxalate intake without any other measures can lead to sustained
      improvement in renal function.

PMID- 28435766
TI  - A Heart too Stiff to Beat: A Case of Familial Transthyretin Amyloidosis
      Cardiomyopathy.
AB  - Heart failure is a common clinical syndrome caused by a variety of cardiac
      diseases. We report a rare case of familial transthyretin amyloidosis
      cardiomyopathy to heighten the awareness of this rare but lethal cause of heart
      failure, as therapeutic interventions such as liver or heart transplant could be
      curative in selected patients.

PMID- 28435768
TI  - Cortical blindness as severe neuro-ophthalmological manifestation of tuberous
      sclerosis complex.
AB  - Patients with retinal lesions related to tuberous sclerous complex (TSC) commonly
      have no impairment of visual acuity. We present a case of a 1-year-old Hispanic
      girl with TSC in which bilateral cortical blindness is documented.

PMID- 28435767
TI  - Green Toxicology: a strategy for sustainable chemical and material development.
AB  - Green Toxicology refers to the application of predictive toxicology in the
      sustainable development and production of new less harmful materials and
      chemicals, subsequently reducing waste and exposure. Built upon the foundation of
      "Green Chemistry" and "Green Engineering", "Green Toxicology" aims to shape
      future manufacturing processes and safe synthesis of chemicals in terms of
      environmental and human health impacts. Being an integral part of Green
      Chemistry, the principles of Green Toxicology amplify the role of health-related
      aspects for the benefit of consumers and the environment, in addition to being
      economical for manufacturing companies. Due to the costly development and
      preparation of new materials and chemicals for market entry, it is no longer
      practical to ignore the safety and environmental status of new products during
      product development stages. However, this is only possible if toxicologists and
      chemists work together early on in the development of materials and chemicals to
      utilize safe design strategies and innovative in vitro and in silico tools. This
      paper discusses some of the most relevant aspects, advances and limitations of
      the emergence of Green Toxicology from the perspective of different industry and
      research groups. The integration of new testing methods and strategies in product
      development, testing and regulation stages are presented with examples of the
      application of in silico, omics and in vitro methods. Other tools for Green
      Toxicology, including the reduction of animal testing, alternative test methods,
      and read-across approaches are also discussed.

PMID- 28435769
TI  - Gambling behavior among Macau college and university students.
AB  - This survey investigated gambling behavior among Chinese students studying in
      Macau colleges and universities. It also aimed to examine the relationship
      between problem gambling, affect states and sensation seeking propensity. A
      convenience sample of 999 students (370 men, 629 women) filled a self
      administered questionnaire consisted of the Problem Gambling Severity Index
      (PGSI) (Ferris and Wynne in The Canadian problem gambling index: User manual.
      Canadian Centre on Substance Abuse, Toronto 2001a), the 8-item Brief Sensation
      Seeking Scale (BSSS-8) (Hoyle et al. Pers Individ Diff 32(3): 401-414, 2002),
      Bradburn's Affect Balance Scale (BABS) (Bradburn in The structure of
      psychological well-being. Aldine, Chicago 1969) and questions on gambling
      activities. The response rate is 65%. Results indicate 32.3% (n = 323) of the
      survey participants wagered on mahjong (61.8%), soccer matches (40.2%), Mark Six
      lottery (37.2%), card games (28.1%), land-based casino gambling (13.1%), slot
      machines (7.5%) and online casino games (2.0%). The average monthly stake was MOP
      $411. Seeking entertainment (18.7%), killing time (12.5%) and peer influence
      (11.1%) were the three main reasons for gambling. Using the PGSI, 3.6 and 5.3% of
      the students could be identified as moderate-risk and problem gamblers
      respectively. Men were significantly more vulnerable to gambling problems (X2(1)
      = 35.00, p < 0.01) than women. Most of the problematic gamblers (76%) made their
      first bet before 14 years. The PGSI scores are significantly correlated with the
      BSSS-8 scores (r = 0.23, p < 0.01) but not with the overall ABS scores (r = 
      0.06, p > 0.05). The study findings inform campus prevention programs and future
      research.

PMID- 28435771
TI  - Brown Adipose Tissue Bioenergetics: A New Methodological Approach.
AB  - The rediscovery of brown adipose tissue (BAT) in humans and its capacity to
      oxidize fat and dissipate energy as heat has put the spotlight on its potential
      as a therapeutic target in the treatment of several metabolic conditions
      including obesity and diabetes. To date the measurement of bioenergetics
      parameters has required the use of cultured cells or extracted mitochondria with
      the corresponding loss of information in the tissue context. Herein, we present a
      method to quantify mitochondrial bioenergetics directly in BAT. Based on XF
      Seahorse Technology, we assessed the appropriate weight of the explants, the
      exact concentration of each inhibitor in the reaction, and the specific
      incubation time to optimize bioenergetics measurements. Our results show that BAT
      basal oxygen consumption is mostly due to proton leak. In addition, BAT presents
      higher basal oxygen consumption than white adipose tissue and a positive response
      to b-adrenergic stimulation. Considering the whole tissue and not just
      subcellular populations is a direct approach that provides a realistic view of
      physiological respiration. In addition, it can be adapted to analyze the effect
      of potential activators of thermogenesis, or to assess the use of fatty acids or
      glucose as a source of energy.

PMID- 28435770
TI  - Thermally Activated Delayed Fluorescence Organic Dots (TADF Odots) for Time
      Resolved and Confocal Fluorescence Imaging in Living Cells and In Vivo.
AB  - The fluorophores with long-lived fluorescent emission are highly desirable for
      time-resolved fluorescence imaging (TRFI) in monitoring target fluorescence. By
      embedding the aggregates of a thermally activated delayed fluorescence (TADF)
      dye, 2,3,5,6-tetracarbazole-4-cyano-pyridine (CPy), in distearoyl-sn-glycero-3
      phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG2000) matrix, CPy-based
      organic dots (CPy-Odots) with a long fluorescence lifetime of 9.3 MUs (in water
      at ambient condition) and high brightness (with an absolute fluorescence quantum
      efficiency of 38.3%) are fabricated. CPy-Odots are employed in time-resolved and
      confocal fluorescence imaging in living Hela cells and in vivo. The green
      emission from the CPy-Odots is readily differentiated from the cellular
      autofluorescence background because of their stronger emission intensities and
      longer lifetimes. Unlike other widely studied DSPE-PEG2000 encapsulated Odots
      which are always distributed in cytoplasm, CPy-Odots are located mainly in plasma
      membrane. In addition, the application of CPy-Odots as a bright microangiography
      agent for TRFI in zebrafish is also demonstrated. Much broader application of CPy
      Odots is also prospected after further surface functionalization. Given its
      simplicity, high fluorescence intensity, and wide availability of TADF materials,
      the method can be extended to develop more excellent TADF Odots for accomplishing
      the challenges in future bioimaging applications.

PMID- 28435772
TI  - Self-Assembled Bifunctional Peptide as Effective Drug Delivery Vector with
      Powerful Antitumor Activity.
AB  - E-cadherin/catenin complex is crucial for cancer cell migration and invasion. The
      histidine-alanine-valine (HAV) sequence has been shown to inhibit a variety of
      cadherin-based functions. In this study, by fusing HAV and the classical tumor
      targeting Arg-Gly-Asp (RGD) motif and Asn-Gly-Arg (NGR) motif to the apoptosis
      inducing peptide sequence-AVPIAQK, a bifunctional peptide has been constructed
      with enhanced tumor targeting and apoptosis effects. This peptide is further
      processed as a nanoscale vector to encapsulate the hydrophobic drug docetaxel
      (DOC). Bioimaging analysis shows that peptide nanoparticles can penetrate into
      xenograft tumor cells with a significantly long retention in tumors and high
      tumor targeting specificity. In vivo, DOC/peptide NPs are substantially more
      effective at inhibiting tumor growth and prolonging survival compared with DOC
      control. Together, the findings of this study suggest that DOC/peptide NPs may
      have promising applications in pulmonary carcinoma therapy.

PMID- 28435773
TI  - Giant Faraday Rotation through Ultrasmall Fe0n Clusters in Superparamagnetic FeO
      SiO2 Vitreous Films.
AB  - Magnetooptical (MO) glasses and, in particular, Faraday rotators are becoming key
      components in lasers and optical information processing, light switching, coding,
      filtering, and sensing. The common design of such Faraday rotator materials
      follows a simple path: high Faraday rotation is achieved by maximizing the
      concentration of paramagnetic ion species in a given matrix material. However,
      this approach has reached its limits in terms of MO performance; hence, glass
      based materials can presently not be used efficiently in thin film MO
      applications. Here, a novel strategy which overcomes this limitation is
      demonstrated. Using vitreous films of xFeO.(100 - x)SiO2, unusually large Faraday
      rotation has been obtained, beating the performance of any other glassy material
      by up to two orders of magnitude. It is shown that this is due to the
      incorporation of small, ferromagnetic clusters of atomic iron which are generated
      in line during laser deposition and rapid condensation of the thin film,
      generating superparamagnetism. The size of these clusters underbids the present
      record of metallic Fe incorporation and experimental verification in glass
      matrices.

PMID- 28435774
TI  - Revelation of Interfacial Energetics in Organic Multiheterojunctions.
AB  - Efficient charge generation via exciton dissociation in organic bulk
      heterojunctions necessitates donor-acceptor interfaces, e.g., between a
      conjugated polymer and a fullerene derivative. Furthermore, aggregation and
      corresponding structural order of polymer and fullerene domains result in
      energetic relaxations of molecular energy levels toward smaller energy gaps as
      compared to the situation for amorphous phases existing in homogeneously
      intermixed polymer:fullerene blends. Here it is shown that these molecular energy
      level shifts are reflected in interfacial charge transfer (CT) transitions and
      depending on the existence of disordered or ordered interfacial domains. It can
      be done so by systematically controlling the order at the donor-acceptor
      interface via ternary blending of semicrystalline and amorphous model polymers
      with a fullerene acceptor. These variations in interfacial domain order are
      probed with luminescence spectroscopy, yielding various transition energies due
      to activation of different recombination channels at the interface. Finally, it
      is shown that via this analysis the energy landscape at the organic
      heterojunction interface can be obtained.

PMID- 28435776
TI  - "Self-Peel-Off" Transfer Produces Ultrathin Polyvinylidene-Fluoride-Based
      Flexible Nanodevices.
AB  - Here, a new strategy, self-peel-off transfer, for the preparation of ultrathin
      flexible nanodevices made from polyvinylidene-fluoride (PVDF) is reported. In
      this process, a functional pattern of nanoparticles is transferred via peeling
      from a temporary substrate to the final PVDF film. This peeling process takes
      advantage of the differences in the work of adhesion between the various layers
      (the PVDF layer, the nanoparticle-pattern layer and the substrate layer) and of
      the high stresses generated by the differential thermal expansion of the layers.
      The work of adhesion is mainly guided by the basic physical/chemical properties
      of these layers and is highly sensitive to variations in temperature and moisture
      in the environment. The peeling technique is tested on a variety of PVDF-based
      functional films using gold/palladium nanoparticles, carbon nanotubes, graphene
      oxide, and lithium iron phosphate. Several PVDF-based flexible nanodevices are
      prepared, including a single-sided wireless flexible humidity sensor in which
      PVDF is used as the substrate and a double-sided flexible capacitor in which PVDF
      is used as the ferroelectric layer and the carrier layer. Results show that the
      nanodevices perform with high repeatability and stability. Self-peel-off transfer
      is a viable preparation strategy for the design and fabrication of flexible,
      ultrathin, and light-weight nanodevices.

PMID- 28435775
TI  - The Mechanical Properties of Nanowires.
AB  - Applications of nanowires into future generation nanodevices require a complete
      understanding of the mechanical properties of the nanowires. A great research
      effort has been made in the past two decades to understand the deformation
      physics and mechanical behaviors of nanowires, and to interpret the discrepancies
      between experimental measurements and theoretical predictions. This review
      focused on the characterization and understanding of the mechanical properties of
      nanowires, including elasticity, plasticity, anelasticity and strength. As the
      results from the previous literature in this area appear inconsistent, a critical
      evaluation of the characterization techniques and methodologies were presented.
      In particular, the size effects of nanowires on the mechanical properties and
      their deformation mechanisms were discussed.

PMID- 28435777
TI  - Recent Progress in Metal-Organic Frameworks for Applications in Electrocatalytic
      and Photocatalytic Water Splitting.
AB  - The development of clean and renewable energy materials as alternatives to fossil
      fuels is foreseen as a potential solution to the crucial problems of
      environmental pollution and energy shortages. Hydrogen is an ideal energy
      material for the future, and water splitting using solar/electrical energy is one
      way to generate hydrogen. Metal-organic frameworks (MOFs) are a class of porous
      materials with unique properties that have received rapidly growing attention in
      recent years for applications in water splitting due to their remarkable design
      flexibility, ultra-large surface-to-volume ratios and tunable pore channels. This
      review focuses on recent progress in the application of MOFs in electrocatalytic
      and photocatalytic water splitting for hydrogen generation, including both oxygen
      and hydrogen evolution. It starts with the fundamentals of electrocatalytic and
      photocatalytic water splitting and the related factors to determine the catalytic
      activity. The recent progress in the exploitation of MOFs for water splitting is
      then summarized, and strategies for designing MOF-based catalysts for
      electrocatalytic and photocatalytic water splitting are presented. Finally, major
      challenges in the field of water splitting are highlighted, and some perspectives
      of MOF-based catalysts for water splitting are proposed.

PMID- 28435778
TI  - Tumor Microenvironment Activable Self-Assembled DNA Hybrids for pH and Redox Dual
      Responsive Chemotherapy/PDT Treatment of Hepatocellular Carcinoma.
AB  - Smart self-assembled "Turn-ON" DNA hybrids are employed, which could respond to
      tumor microenvironment stimuli for cancer cell specific real-time fluorescence
      imaging, tumor-specific synergistic photodynamic therapy and chemotherapy in
      hepatocellular carcinoma.

PMID- 28435779
TI  - Sodium-Ion Batteries: Improving the Rate Capability of 3D Interconnected Carbon
      Nanofibers Thin Film by Boron, Nitrogen Dual-Doping.
AB  - Boron, nitrogen dual-doping 3D hard carbon nanofibers thin film is synthesized
      using a facile process. The nanofibers exhibit high specific capacity and
      remarkable high-rate capability due to the synergistic effect of 3D porous
      structure, large surface area, and enlarged carbon layer spacing, and the B, N
      codoping-induced defects.

PMID- 28435780
TI  - Highly Active and Stable Pt-Pd Alloy Catalysts Synthesized by Room-Temperature
      Electron Reduction for Oxygen Reduction Reaction.
AB  - Carbon-supported platinum (Pt) and palladium (Pd) alloy catalyst has become a
      promising alternative electrocatalyst for oxygen reduction reaction (ORR) in
      proton exchange membrane fuel cells. In this work, the synthesis of highly active
      and stable carbon-supported Pt-Pd alloy catalysts is reported with a room
      temperature electron reduction method. The alloy nanoparticles thus prepared show
      a particle size around 2.6 nm and a core-shell structure with Pt as the shell.
      With this structure, the breaking of O-O bands and desorption of OH are both
      promoted in electrocatalysis of ORR. In comparison with the commercial Pt/C
      catalyst prepared by conventional method, the mass activity of the Pt-Pd/C
      catalyst for ORR is shown to increase by a factor of ~4. After 10 000-cycle
      durability test, the Pt-Pd/C catalyst is shown to retain 96.5% of the mass
      activity, which is much more stable than that of the commercial Pt/C catalyst.

PMID- 28435781
TI  - Carbon Nanotubes in TiO2 Nanofiber Photoelectrodes for High-Performance
      Perovskite Solar Cells.
AB  - 1D semiconducting oxides are unique structures that have been widely used for
      photovoltaic (PV) devices due to their capability to provide a direct pathway for
      charge transport. In addition, carbon nanotubes (CNTs) have played
      multifunctional roles in a range of PV cells because of their fascinating
      properties. Herein, the influence of CNTs on the PV performance of 1D titanium
      dioxide nanofiber (TiO2 NF) photoelectrode perovskite solar cells (PSCs) is
      systematically explored. Among the different types of CNTs, single-walled CNTs
      (SWCNTs) incorporated in the TiO2 NF photoelectrode PSCs show a significant
      enhancement (~40%) in the power conversion efficiency (PCE) as compared to
      control cells. SWCNTs incorporated in TiO2 NFs provide a fast electron transfer
      within the photoelectrode, resulting in an increase in the short-circuit current
      (Jsc) value. On the basis of our theoretical calculations, the improved open
      circuit voltage (Voc) of the cells can be attributed to a shift in energy level
      of the photoelectrodes after the introduction of SWCNTs. Furthermore, it is found
      that the incorporation of SWCNTs into TiO2 NFs reduces the hysteresis effect and
      improves the stability of the PSC devices. In this study, the best performing PSC
      device constructed with SWCNT structures achieves a PCE of 14.03%.

PMID- 28435782
TI  - Thoracic Ultrasound: What Non-radiologists Need to Know.
AB  - PURPOSE OF REVIEW: The aim of this review is to provide the theoretical and
      practical knowledge essential for non-radiologists to develop the skills
      necessary to apply thoracic ultrasound as an extension of clinical assessment and
      intervention. RECENT FINDINGS: Issues relating to training and competence are
      discussed and a library of thoracic ultrasound videos is provided to illustrate
      artefacts, pleural, parenchymal and pneumothorax pathology as well as important
      pitfalls to consider. Novel and future diagnostic applications of thoracic
      ultrasound in the setting of acute cardiorespiratory pathology including
      consolidation, acute interstitial syndromes and pulmonary embolism are explored.
      SUMMARY: Thoracic ultrasound requires an understanding of imaging artefact
      specific to lung and pleura and a working knowledge of machine knobology for
      image optimisation and interpretation. Ultrasound is a valuable tool for the
      practicing chest clinician providing diagnostic information for the assessment of
      pleural and parenchymal disease and increased safety and cost effectiveness of
      thoracic interventions.

PMID- 28435783
TI  - Hypertension among Asians in Los Angeles County: Findings from a multiyear
      survey.
AB  - Few studies have examined the prevalence of hypertension among Asians living in
      the United States. Multiyear data from the Los Angeles County Health Survey were
      used to investigate the prevalence of hypertension among Asians and Asian
      subgroups, and risk factors associated with the disease, using descriptive
      analysis and multivariate logistic regression. Age-adjusted prevalence of
      hypertension in Asians was 23.4%. Among Asian subgroups, age-adjusted prevalence
      of hypertension was lowest among Chinese (20.0%), and highest among Filipinos
      (32.7%), and several factors were identified as associated with hypertension.
      Hypertension among Asian-Americans is a serious public health concern, requiring
      culturally sensitive best practices, and evidence-based approaches to improve
      prevention and control among Asians.

PMID- 28435784
TI  - School food environment: Quality and advertisement frequency of child-oriented
      packaged products within walking distance of public schools.
AB  - Food marketing for children is a major concern for public health nutrition and
      many schools make efforts to increase healthy eating. Food environments
      surrounding schools in urban areas may undermine these efforts for healthy
      nutrition within school programs. Our study aim is to describe the nutrition
      environment within walking distance of schools in terms of food quality and food
      marketing and to explore the degree to which elements of the nutrition
      environment varies by proximity to schools. In a cross-sectional study, we
      analyzed the surrounding food environments of a convenience sample of 46 target
      schools within 950m walking distance in 7 different urban districts across
      Vienna, Austria. In total, we analyzed data from 67 fast food outlets and 54
      supermarkets analyzing a total of 43.129 packaged snack food and beverage
      products, from which 85% were for adults and 15% of the products were child
      oriented. Proximity to the schools did not affect the availability of child
      oriented products and dedicated food advertisements for children. After applying
      nutrient profiling using the Nutrient Profiling Model (NPM) on child-oriented
      products, results showed that 15.8% of the packaged snack food were categorized
      as "healthy" foods and 84.2% as "less healthy"; for beverages 65.7% were
      categorized as "healthy" and 34.3% as "less healthy". In conclusion, our results
      show that child-oriented snacks are not more frequently advertised around schools
      but substantially lack in nutritional quality with the potential to undermine
      efforts for promoting healthy eating practices within schools.

PMID- 28435786
TI  - Mediastinal liposarcoma in a 30-year-old woman with dyspnea and chest pain.
AB  - Mediastinal liposarcoma (ML) is a rare mesenchymal tumor, accounting for less
      than 1% of mediastinal tumors. They have a slow growth, so they may not give
      symptoms for a long time, until the tumor produces compression of close
      structures. The treatment of choice is surgery, which can be combined with chemo
      radiotherapy. We present a case in which the diagnosis of a ML was made in a 30
      year-old woman with dyspnea and chest pain.

PMID- 28435785
TI  - Impact of a brief intervention on cervical health literacy: A waitlist control
      study with jailed women.
AB  - Jailed women are four-five times more likely to have had cervical cancer compared
      to women without criminal justice histories. Previous research has shown that an
      important contributor to cervical cancer risk, and perhaps lack of follow-up, is
      incarcerated women's low health literacy about broader reproductive health
      issues. Little work has been done to address this disparity. Thus, the objective
      of this study was to test the effectiveness of an intervention to improve
      incarcerated women's cervical health literacy and ultimately address cervical
      cancer disparities. Using a waitlist control design, we compared changes in
      cervical health literacy (knowledge, beliefs, self-efficacy, and confidence for
      screening and follow-up) among 188 incarcerated women who completed a 10-hour
      intervention between 2014 and 2016 in three Kansas City jails. We used bivariate
      tests and multivariate analyses that controlled for baseline cervical health
      literacy level and key covariates. Women in the intervention group showed
      significant gains in seven out of eight cervical health literacy domains (all p <
      0.01), whereas the control group only improved in one domain (p < 0.01). When
      controlling for covariates, the intervention group had less barriers, perceptions
      of seriousness, susceptibility to disease, and increased self-efficacy for
      cervical health screening and follow-up, compared to the control group (all p <
      0.05). A brief intervention is an effective way to improve jailed women's
      cervical health literacy, but should be provided alongside systemic efforts that
      expand access to correctional preventive health services, including the human
      papillomavirus vaccine, community-based cancer screenings, and health insurance
      after women leave jails and transition back to communities.

PMID- 28435787
TI  - High Grade Mucinous Urothelial Carcinoma of the Renal Collecting System: A Case
      Report.
AB  - High grade mucinous urothelial carcinoma is a rare pathological variant. There is
      still controversy as to its nomenclature and classification. We report the case
      of a 64 year old female with history of pelvic pain who was incidentally
      discovered to have a left upper pole renal mass. Left nephroureterectomy was
      performed and histopathological examination revealed high grade mucinous
      urothelial carcinoma. Accurate diagnosis of this distinct pathological entity
      will allow for better understanding of phenotypic behavior and inform best
      treatment strategies.

PMID- 28435788
TI  - Laparoscopic Repair of a Vesicosigmoid Fistula Secondary to Holmium Laser
      Enucleation of the Prostate (HoLEP).
AB  - Holmium Laser Enucleation of the Prostate (HoLEP) is a safe and effective
      treatment option for benign prostatic hyperplasia. However, in some cases, it can
      lead to life-threatening complications. In particular, morcellation of the
      resected adenoma may be a very dangerous procedure when performed without clear
      visualization. We describe the first reported case of a vesicosigmoid fistula
      secondary to a morcellation injury during HoLEP.

PMID- 28435789
TI  - Aerococcus urinae: An Emerging Cause of Urinary Tract Infection in Older Adults
      with Multimorbidity and Urologic Cancer.
AB  - Aerococcus urinae is a rare organism isolated from urine cultures. We present a
      case of an 80 year-old male with bladder cancer and multimorbidity who developed
      A. urinae infection. A. urinae may cause simple and complicated UTIs, bacteremia,
      and endocarditis in older adults with multimorbidity, chronic urinary retention,
      or indwelling catheters. A. urinae treatment should employ penicillin,
      amoxicillin, and nitrofurantoin. Due to increasing antibiotic resistance, urine
      culture should include antibiotic susceptibility testing. Prompt and culture
      specific treatment is critical to avoid clinical progression of the infection.

PMID- 28435790
TI  - A Rare Case of Epididymal Abscess in an Infant Treated Successfully with Needle
      Aspiration.
AB  - A 5-month-old boy presented with right scrotal swelling. Color Doppler
      ultrasonography showed an encapsulated hypoechoic lesion with surrounding
      hyperemia in the right tail of the epididymis. We performed surgical exploration
      of the scrotum because it was not considered to be a typical epididymitis. During
      the operation, we aspirated pus from his right epididymis through a needle by
      referring to the color Doppler findings. This is the first case of epididymal
      abscess in an infant to be successfully diagnosed and treated with needle
      aspiration.

PMID- 28435791
TI  - Emphysematous Pyelonephritis with Renal Artery Pseudoaneurysm.
AB  - Emphysematous pyelonephritis is an acute infection of the renal parenchyma and
      perinephric tissues caused by gas-forming microorganisms, resulting in the
      radiographic presence of gas in the kidney, collecting system, and surrounding
      spaces. Here we present a case of severe emphysematous pyelonephritis in the
      setting of Klebsiella urosepsis. Surgical exploration of the flank revealed
      infectious disintegration of the renal parenchyma into a large phlegmon. The post
      operative course was complicated by renal artery pseudoaneurysm and cutaneous
      fistualization of a perinephric fluid collection. Despite the high rate of
      mortality associated with this condition, the patient survived and has remained
      clinically well.

PMID- 28435792
TI  - Retroperitoneoscopic Partial Nephrectomy for a Horseshoe Kidney Tumor.
AB  - Horseshoe kidney is the most common renal fusion anomaly found in about 0.15% to
      0.25% of the population. Renal cell carcinoma associated with a horseshoe kidney
      has been described in fewer than 200 cases. Its incidence and prognosis seems to
      be not different from those of the general population, but surgical management
      may be challenging due to unique anatomic features of horseshoe kidneys, such as
      highly variable vasculature. We report a case of a 69-year-old male with an
      incidental 48-mm solid mass in the left moiety of a horseshoe kidney,
      successfully treated by retroperitoneoscopic partial nephrectomy.

PMID- 28435793
TI  - Metastatic Renal Cell Carcinoma to Jejunum: An Unusual Case Presentation.
AB  - The small intestine is a very uncommon and peculiar site for metastasis from
      renal cell carcinoma (RCC). We present a clinical presentation of insidious and
      unusual development of a jejunal metastasis while having stable disease in a
      remainder of metastatic sites, in a patient undergoing immunotherapy with
      nivolumab. Due to the extreme rarity of metastatic renal cell carcinoma to the
      lumen of the small bowel, it is easy to overlook and misdiagnose symptoms of this
      pathologic entity, particularly when the remainder of metastatic disease responds
      well to ongoing therapy.

PMID- 28435795
TI  - Editorial.

PMID- 28435794
TI  - Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.
AB  - CONTEXT: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal
      dominant cancer syndrome characterized in part by metastatic medullary thyroid
      cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous
      hypercortisolism in children. CASE DESCRIPTION: We describe a 21-year-old African
      American male who was diagnosed at age 10 with an ACTH-secreting pituitary
      microadenoma. At age 16 he developed medullary thyroid cancer and was found to
      have multiple endocrine neoplasia type 2B with the characteristic M918T mutation
      of the RET proto-oncogene. Following thyroidectomy, he was initiated on
      Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over
      the last 5 years. CONCLUSIONS: Our patient is the first individual with MEN2B to
      be described with Cushing disease. The RET oncogene may play a role in pituitary
      tumorigenesis; alternatively, the coexistence of these two entities may represent
      an extremely rare coincidence.

PMID- 28435796
TI  - Isolation and partial purification of erythromycin from alkaliphilic Streptomyces
      werraensis isolated from Rajkot, India.
AB  - An alkaliphilic actinomycete, BCI-1, was isolated from soil samples collected
      from Saurashtra University campus, Gujarat. Isolated strain was identified as
      Streptomyces werraensis based on morphological, biochemical and phylogenetic
      analysis. Maximum antibiotic production was obtained in media containing sucrose
      2%, Yeast extract 1.5%, and NaCl 2.5% at pH 9.0 for 7 days at 30  degrees C.
      Maximum inhibitory compound was produced at pH 9 and at 30  degrees C. FTIR
      revealed imine, amine, alkane (C 000000000000 000000000000 000000000000
      111111111111 000000000000 111111111111 000000000000 000000000000 000000000000 C)
      of aromatic ring and p-di substituted benzene, whereas HPLC analysis of partially
      purified compound and library search confirmed 95% peaks matches with
      erythromycin. Chloroform extracted isolated compound showed MIC values 1 MUg/ml
      against Bacillus subtilis, <=0.5 MUg/ml against Staphylococcus aureus, <=0.5
      MUg/ml against Escherichia coli and 2.0 MUg/ml against Serretia GSD2 sp., which
      is more effective in comparison to ehtylacetate and methanol extracted compounds.
      The study holds significance as only few alkaliphilic actinomycetes have been
      explored for their antimicrobial potential.

PMID- 28435797
TI  - A novel marine bacterium Isoptericola sp. JS-C42 with the ability to
      saccharifying the plant biomasses for the aid in cellulosic ethanol production.
AB  - The ever growing demands for food products such as starch and sugar produces;
      there is a need to find the sources for saccharification for cellulosic
      bioethanol production. This study provides the first evidence of the
      lignocellulolytic and saccharifying ability of a marine bacterium namely
      Isoptericola sp. JS-C42, a Gram positive actinobacterium with the cocci cells
      embedded on mycelia isolated from the Arabian Sea, India. It exhibited highest
      filter paper unit effect, endoglucanase, exoglucanase, cellobiohydrolase, beta
      glucosidase, xylanase and ligninase effect. The hydrolytic potential of the
      enzymes displayed the efficient saccharification capability of steam pretreated
      biomass. It was also found to degrade the paddy, sorghum, Acacia mangium and
      Ficus religiosa into simple reducing sugars by its efficient lignocellulose
      enzyme complex with limited consumption of sugars. Production of ethanol was also
      achieved with the Saccharomyces cerevisiae. Overall, it offers a great potential
      for the cellulosic ethanol production in an economically reliable and eco
      friendly point-of-care.

PMID- 28435798
TI  - Treatment strategies for high resveratrol induction in Vitis vinifera L. cell
      suspension culture.
AB  - Bioprocesses capable of producing large scales of resveratrol at nutraceutical
      grade are in demand. This study herein investigated treatment strategies to
      induce the production of resveratrol in Vitis vinifera L. cell suspension
      cultures. Among seven investigated elicitors, jasmonic acid (JA), salicylic acid,
      beta-glucan (GLU), and chitosan enhanced the production of intracellular
      resveratrol manyfold. The combined treatment of JA and GLU increased
      extracellular resveratrol production by up to tenfold. The application of
      Amberlite XAD-7 resin for in situ removal and artificial storage of secreted
      resveratrol further increased resveratrol production by up to four orders of
      magnitude. The level of resveratrol produced in response to the combined
      treatment with 200 g/L XAD-7, 10 MUM JA and 1 mg/mL GLU was approximately 2400
      mg/L, allowing the production of resveratrol at an industrial scale. The high
      yield of resveratrol is due to the involvement of a number of mechanisms working
      in concert.

PMID- 28435799
TI  - Comparison of the behavior of CHO cells during cultivation in 24-square deep well
      microplates and conventional shake flask systems.
AB  - In biopharmaceutical production, the optimization of cell culture media and
      supplementation is a vital element of process development. Optimization is
      usually achieved through the screening of multiple media, feed and feeding
      strategies. However, most screening is performed in shake flasks, which makes the
      screening process very time consuming and inefficient. The use of small scale
      culture systems for the screening process can aid in the ability to screen
      multiple formulations during process development. In order to assess the
      suitability of 24 deep well (24DW) plates with the Duetz sandwich-covers as a
      small scale culture system for process development, we have tested growth and
      production performance of CHO cells in 24DW plates and conventional shake flask
      cultures. Multiple studies were performed to assess well-to-well and plate-to
      plate variability in 24DW plates. Additional studies were performed to determine
      the applicability of 24DW plates for cell culture medium and supplement screening
      in batch and fed batch processes. Cultures in 24DW plates exhibited similar
      kinetics in growth, viability and protein production to those cultured in shake
      flasks, suggesting that 24DW plates with Duetz sandwich-covers can be effectively
      used for high throughput cell culture screening.

PMID- 28435800
TI  - Antioxidative activity of different parts of the plant Lepidium sativum Linn.
AB  - Lepidium sativum Linn. has been used in traditional and folklore medicine for the
      treatment of bronchial asthma, diabetes, local and rheumatic pain. An ethanolic
      extract of cress (L. sativum L.) shoot, leaf, stem and seed has been studied for
      antioxidative active against 1,1-diphenyl-2-picrylhydrazyl (DPPH), total
      glutathione S-transferase assay, reduced glutathione activity, reducing power
      (Fe3+-Fe2+ Transformation Ability), and ascorbic acid is also estimated. The
      percentage yields of free radical scavenging activity (DPPH) obtained for
      different ethanolic extracts of L. sativum. Supreme scavenging activity was
      detected in shoot (12.19 +/- 02%) and least in stem (2.69 +/- 05%). The activity
      of total glutathione S-transferase enzyme was found to be more in seed (9600 +/-
      56.3 MUg/ml) than other plant parts. The reduced glutathione content of the
      ethanolic extracts of L. sativum was found to be more in leaf (9 +/- 0.2 MUg/ml).
      In the reducing power assay, ethanolic extracts gives the optical density in
      increasing concentration in all plant parts it shows that it has the reducing
      ability of Fe3+-Fe2+. Presence of vitamin C was tested. It was found that the
      shoot extract has highest amount of vitamin C. The results of present data were
      shown that the ethanolic extract of L. sativum L. plant parts have contributed
      high potential in vitro antioxidant activity.

PMID- 28435801
TI  - Molecular identification of sex in Simarouba glauca by RAPD markers for crop
      improvement strategies.
AB  - Due to lack of morphological methods to identify sex at early stage in the plants
      with long juvenile period the application of molecular markers is expected to
      facilitate breeding program. The objective of this study is to identify molecular
      markers linked to sex determination of the plant Simarouba glauca which assists
      in crop improvement program. Random amplified polymorphic DNA primers were tested
      on dioeceious and hermaphrodite plant Simarouba glauca. A set of eighty five RAPD
      primers were screened out of which only five primers were found to be associated
      with sex. The primer OPU-10 is male specific and OPD-19 primer is female
      specific. Another primer OPU-19 produced a unique amplification in only
      hermaphrodite individuals. Female and hermaphrodite specific primer OPS-05
      amplified an amplicon in female and hermaphrodite and was absent in male plant.
      Primer OPW-03 produced amplicon specific to male and hermaphrodite plants and was
      absent in female plants.

PMID- 28435802
TI  - Prospective technologies, feedstocks and market innovations for ethanol and
      biodiesel production in the US.
AB  - In recent years, production and consumption of biofuels has become controversial,
      mainly due to the competitive use of natural resources for food/feed and fuel
      production. Second generation biofuels (with cellulosic ethanol being on top of
      developments nowadays) have a great potential to provide an economically feasible
      solution. However, high processing costs related to breaking down cellulosic
      plant material and converting it to sugar (and fuel), missing infrastructure and
      environmental impacts can be detrimental. This paper discusses various biofuels
      technologies and feedstocks that have a potential to emerge as prospective
      feedstocks for second generation biofuels production in the future on the US
      market. It also emphasizes existing challenges that could hinder the development
      of these technologies and their commercialization in the long-term.

PMID- 28435803
TI  - Micro-compartmentalized cultivation of cyanobacteria for mutant screening using
      glass slides with highly water-repellent mark.
AB  - Photosynthetic microorganisms such as cyanobacteria have attracted attention for
      their potential to produce biofuels and biochemicals directly from CO2. Cell
      isolation by colony has conventionally been used for selecting target cells.
      Colony isolation methods require a significant amount of time for cultivation,
      and the colony-forming ratio is potentially low for cyanobacteria. Here, we
      overcome such limitations by encapsulating and culturing cells in droplets with
      an overlay of dodecane using glass slides printed with highly water-repellent
      mark. In the compartmentalized culture, the oil phase protects the small volume
      of culture medium from drying and increases the CO2 supply. Since a difference in
      cell growth was observed with and without the addition of antibiotics, this
      compartmentalized culture method could be a powerful tool for mutant selection.

PMID- 28435805
TI  - Theoretical methane production generated by the co-digestion of organic fraction
      municipal solid waste and biological sludge.
AB  - The co-digestion of two problematic and available wastes, namely Organic Fraction
      Municipal Solid Waste (OFMSW) and biological sludge, was carried out in this
      work. Biochemical Methane Potential (BMP) tests are a useful tool for determining
      the best substrate and co-digestion configurations, however there are some
      methodologies destined to save costs and time from this process by using the
      theoretical final methane potential of a substrate from its organic composition.
      Besides there are some models capable not only of reproducing the methane curve
      behavior, but also of predicting final methane productions from the first days of
      experimentation. Methodologies based in the elemental composition for the
      determination of theoretical production fit better with the experimental results
      and behavior, nevertheless the Gompertz model was capable of predicting the final
      productivity within the 7th day of experiment, selecting at the same time the co
      digestion of 80% OFMSW and 20% Biological sludge as the optimum.

PMID- 28435804
TI  - Resveratrol production in bioreactor: Assessment of cell physiological states and
      plasmid segregational stability.
AB  - Resveratrol is a plant secondary metabolite commonly found in peanuts and
      grapevines with significant health benefits. Recombinant organisms can produce
      large amounts of resveratrol and, in this work, Escherichia coli BW27784 was used
      to produce resveratrol in bioreactors while monitoring cell physiology and
      plasmid stability through flow cytometry and real-time qPCR, respectively.
      Initially, the influence of culture conditions and precursor addition was
      evaluated in screening assays and the data gathered was used to perform the
      bioreactor assays, allowing the production of 160 MUg/mL of resveratrol. Cellular
      physiology and plasmid instability affected the final resveratrol production,
      with lower viability and plasmid copy numbers associated with lower yields. In
      sum, this study describes new tools to monitor the bioprocess, evaluating the
      effect of culture conditions, and its correlation with cell physiology and
      plasmid segregational stability, in order to define a viable and scalable
      bioprocess to fulfill the need for larger quantities of resveratrol.

PMID- 28435806
TI  - SV40 VP1 major capsid protein in its self-assembled form allows VP1 pentamers to
      coat various types of artificial beads in vitro regardless of their sizes and
      shapes.
AB  - The icosahedral capsid structure of simian virus 40 (diameter, 45 nm) consists of
      72 pentameric subunits, with each subunit formed by five VP1 molecules. Electron
      microscopy, immuno-gold labeling, and zeta-potential analysis showed that
      purified recombinant VP1 pentamers covered polystyrene beads measuring 100, 200,
      and 500 nm in diameter, as well as silica beads. In addition to covering
      spherical beads, VP1 pentamers covered cubic magnetite beads, as well as the
      distorted surface structures of liposomes. These findings indicate that VP1
      pentamers could coat artificial beads of various shapes and sizes larger than the
      natural capsid. Technology based on VP1 pentamers may be useful in providing a
      capsid-like surface for enclosed materials, enhancing their stability and
      cellular uptake for drug delivery systems.

PMID- 28435807
TI  - A simple and highly efficient Agrobacterium-mediated transformation protocol for
      Setaria viridis.
AB  - The production and use of sugarcane in Brazil is very important for bioenergy
      production and is recognized as one of the most efficient in the world. In our
      laboratory, Setaria viridis is being tested as a model plant for sugarcane. S.
      viridis has biological attributes (rapid life cycle, small genome, diploid, short
      stature and simple growth requirements) that make it suitable for use as a model
      system. We report a highly efficient protocol for Agrobacterium-mediated genetic
      transformation of S. viridis. The optimization of several steps in tissue culture
      allowed the rapid regeneration of plants and increased the rate of transformation
      up to 29%. This protocol could become a powerful tool for functional genomics in
      sugarcane.

PMID- 28435808
TI  - A perspective on the economic valorization of gene manipulated biotechnology:
      Past and future.
AB  - Three distinct fields of gene manipulated biotechnology have so far been
      economically exploited: medical biotechnology, plant biotechnology and industrial
      biotechnology. This article analyzes the economic evolution and its drivers in
      the three fields over the past decades, highlighting strong divergences. Product
      and market characteristics, affecting firms' financing options, are shown to be
      important enablers or inhibitors. Subsequently, the lack of commercialization in
      a fourth type of gene manipulated biotechnology, namely environmental
      biotechnology, is explained by the existence of strong barriers. Given the
      latter's great promises for environmental sustainability, we argue for a need to
      push the commercial valorization of environmental biotechnology. Our research has
      strong implications for (technology) management research in biotechnology,
      pointing to a need to control for and/or distinguish between different
      biotechnology fields.

PMID- 28435809
TI  - Setaria viridis floral-dip: A simple and rapid Agrobacterium-mediated
      transformation method.
AB  - Setaria viridis was recently described as a new monocotyledonous model species
      for C4 photosynthesis research and genetic transformation. It has biological
      attributes (rapid life cycle, small genome, diploid, short stature and simple
      growth requirements) that make it suitable for use as a model plant. We report an
      alternative method of S. viridis transformation using floral dip to circumvent
      the necessity of tissue culture phase for transgenic plant regeneration. S.
      viridis spikes at boot stage were selected to be immersed in Agrobacterium
      suspension. T1 seeds could be identified in 1.5-2 months after floral dipping. We
      demonstrated through molecular analysis and RFP expression that seeds and
      resulting plants from dipped inflorescences were transformed. Our results suggest
      the feasibility of S. viridis floral dip transformation as a time-saving and cost
      effective compared with traditional methods. To our knowledge, this is the first
      report using floral dip in S. viridis as an Agrobacterium-mediated transformation
      method.

PMID- 28435810
TI  - Fermentative production and optimization of mevastatin in submerged fermentation
      using Aspergillus terreus.
AB  - The main objective of the study is to enhance the mevastatin production using
      Plackett-Burman (PB) and central composite design (CCD) by Aspergillus terreus in
      submerged fermentation (SmF). Eight nutrients were chosen for a PB design with 12
      experimental runs. A maximum mevastatin production of 170.4 mg L-1 was obtained
      in PB design. Response surface methodology (RSM) is a sequential procedure with
      an initial objective to lead the experimenter rapidly and efficiently along a
      path of improvement toward the general vicinity of the optimum. The individual
      and interactive effects of these variables were studied by conducting the
      fermentation run at randomly selected and different levels of all five factors.
      Experiments were conducted to optimize the medium constituents like glycerol,
      CuCl2.2H2O, FeSO4.7H2O, KH2PO4 and MgSO4.7H2O. At the optimum condition, a
      maximum mevastatin production of 701 mg L-1 was obtained.

PMID- 28435811
TI  - Development of Conceptual Framework to Understand Factors Associated with Return
      to Work among Cancer Survivors: A Systematic Review.
AB  - This systematic review was conducted to develop a conceptual framework that
      addresses various factors associated with return to work among cancer survivors.
      Databases Medline, EMBASE, ProQuest, PubMed and ScienceDirect were systematically
      searched using medical subject headings [MeSH] for studies published in English
      from 1990 to 2013. Studies that described adult cancer patients' self-reported
      data or patients' point of view on factors associated with return to work or
      employment status following cancer diagnosis were included. Articles selection
      was conducted in three steps: selection based on title and abstract, retrieval of
      full text and additions of articles from reference lists and recommendations from
      experts. Disagreement in data extraction was solved by consultation of third
      reviewer. Out of twenty seven articles, breast cancer was the most studied type
      of cancer (30%) while colorectal cancer was studied independently in two articles
      (7.4%). Conceptual framework on return to work identifies factors under
      environmental, personal, work demand, work ability, health status and financial
      factors. Extensive search of scientific databases over last 24 years and the
      development of the conceptual frame-work are the strength of this review.
      Conceptual framework reveals the various factors including non-medical factors
      associated with return to work upon cancer diagnosis. It serves as a reminder to
      the policy makers to focus on modifiable factors as potential areas for
      intervention to assist cancer survivors return to work, especially those with
      little financial assistance and health insurance.

PMID- 28435813
TI  - Medical Care or Disciplinary Discourses? Preventive Measures against the Black
      Death in Late Medieval Paris: A Brief Review.
AB  - BACKGROUND: This paper examined the political and social implications of the
      Compendium de epidemia prescription written by the Masters of the Faculty of
      Medicine of the University of Paris in the mid-14th century during the Black
      Death. This study aimed to examine how the effects of power as a discourse owned
      by medical knowledge are revealed. METHODS: This paper outlines the composition
      of the contents based on the 1888 edition edited and translated by Emile H.
      Rebouis and notes the features of the prescription examined by the existing study
      of medical history rather than the causes of diseases. RESULTS: Compendium de
      epidemia seems to have been written primarily for the royal family and nobles who
      ordered them when looking at prescription-related technologies. At the same time,
      under the influence of Islamic-Arabic academia, it clearly distinguishes the
      world of faith and the world of academia (intelligence), explaining the
      pathogenesis and infection pathways based on causality. The onset substrate is
      due to heat and humidity, and the prescription is to prevent the two from
      overdoing in the body. In particular, issues related to heat are criticized in
      connection with the value of life of knight-noblesse. This is in response to
      political criticism of the ineffectual French royal family and nobility at the
      beginning of the Hundred Years' War and shows why this tract sets the utilitas
      publica at the forefront as an important purpose. CONCLUSION: The conclusion has
      shown how medical knowledge produced on the Black Death pandemic how they
      function as discourses that have a sort of power effect on the value of life of
      knight-noblesse. It is necessary to conduct if these phenomena can be found in
      other contemporary medical writings.

PMID- 28435812
TI  - Scientometrics on Public Health Research in Iran: Increase of Area Studies
      despite Embargoes? A Review Article.
AB  - BACKGROUND: Due to embargoes and sanctions from 1979 until 2015, impact on
      scientific research in Iran may be critical. Public health is the main example of
      this burning point. In this paper, the aim was to map the scientific research in
      public health in Iran until 2014 with area studies as well as networks of
      countries involved. METHODS: We used bibliographic analyses using VOS viewer
      software for network analysis during the period 1975-2014. Two databases were
      used: Web of Science and PubMed. We performed analyses of journals, authors,
      publication years, organizations, funding companies, countries, keywords and Web
      of sciences Categories. RESULTS: We accessed 862 articles published between 1991
      and 2014, the majority of published after 2008. The main countries of research
      were Iran, the United States of America, England, and Sweden and represented the
      main network collaboration. The main Web of Sciences categories was public,
      occupational and environmental health, medicine general internal and
      parasitology. We accessed 25462 publications on PubMed database from 1950 to
      2014. The majority of published after 2004. The main area studies were prognosis,
      wounds and injuries, soil solutions and biological markers. CONCLUSION: Public
      health research in Iran has been developed since 2004. The chief field was
      emerging cardiovascular diseases and communicable diseases. Other
      biotechnological fields were emerging such as biological markers research. Iran
      provides structures to face up with its new challenges using networks of
      countries such as the USA, England, and Sweden. End of embargoes could provide
      new perspectives for public health research and more largely scientific research
      in Iran.

PMID- 28435814
TI  - Gender-dependent Differences in the Relationship between Diabetes Mellitus and
      Ambient Air Pollution among Adults in South Korean Cities.
AB  - BACKGROUND: Air pollution has been a serious public health threat worldwide. It
      has been linked to pulmonary and cardiovascular diseases but is also believed to
      contribute to air-pollution-mediated cardiometabolic disease such as diabetes. We
      investigated the relationship between type 2 diabetes mellitus (DM2) and air
      pollution in densely developed urban settings in South Korea, using national
      epidemiologic data. METHODS: The analysis focused on examining gender-related
      differences in the relationship between DM 2 and air pollutants, specifically
      particulate matter <= 10MUm (PM10) and sulfur dioxide (SO2). To assess the
      relationship between DM and exposure to PM10 and SO2, multivariate logistic
      regression models were developed using the 2012 Korea Community Health Survey
      data and the ambient air pollution data in South Korean cities at both Gu- and Si
      levels. RESULTS: The commonly encountered levels of PM10 and SO2 may be
      associated with DM 2 prevalence in South Korea but it appears there may be gender
      differences. In particular, exposure to either PM10 or SO2 was significantly
      related to the prevalence of DM 2 among women but not among men. CONCLUSION:
      These findings provide new evidence of an association between air pollution and
      the risk of diabetes in urbanized areas of South Korea.

PMID- 28435815
TI  - Perception of HIV/AIDS Education at the Community Level in Jordan.
AB  - BACKGROUND: The control of spread of HIV takes concerted efforts at both national
      and international levels. Education is an important component of preventing the
      spread of HIV. This study aimed to assess the attitudes of parents, teachers and
      students towards informing children about HIV/AIDS, attitudes concerning 'proper'
      age to learn about HIV/AIDS, possible differences in attitudes relating to gender
      of child and what they should learn and ideas about the most 'adequate'
      person/institution to be responsible for provision of HIV/AIDS education.
      METHODS: This study was conducted in Amman, Jordan in April 2015. Descriptive
      correlational design was used; a sample of school students, university students,
      school teachers and parents, a stratified random sample was used. Data was
      collected by using a questionnaire. RESULTS: All groups asserted the importance
      of HIV/AIDS education and awareness rising for all. 62.0% of respondents thought
      that school was the main source of information. About 82% of respondents believed
      that HIV/AIDS education should be integrated into different disciplines of school
      curricula, 84% of respondents believed that HIV/AIDS education should be part of
      university curricula. Nobody believed that HIV/AIDS education should be
      restricted to boys only. CONCLUSION: As HIV/AIDS is a scary matter to all,
      stigmatization and shame may be behind potentially bigger numbers of infected or
      ill people who do not come forward for treatment or care. Attitudes of their kin
      care providers need to be addressed as well as those of the official health care
      providers.

PMID- 28435816
TI  - A Risk Assessment Comparison of Breast Cancer and Factors Affected to Risk
      Perception of Women in Turkey: A Cross-sectional Study.
AB  - BACKGROUND: The increase in breast cancer incidence has enhanced attention
      towards breast cancer risk. The aim of this study was to determine the risk of
      breast cancer and risk perception of women, factors that affect risk perception,
      and to determine differences between absolute risk and the perception of risk.
      METHODS: This cross-sectional study was carried out among 346 women whose score
      in the Gail Risk Model (GRM) was >= 1.67% and/or had a 1st degree relative with
      breast cancer in Bahcesehir town in Istanbul, Turkey between Jul 2012 and Dec
      2012. Data were collected through face-to-face interviews. The level of risk for
      breast cancer has been calculated using GRM and the Breast Cancer Risk Assessment
      Form (BCRAF). Breast cancer risk perception (BCRP), has been evaluated by visual
      analogue 100-cm-long scale. RESULTS: Even though 39.6% of the women considered
      themselves as high-risk carriers, according to the GRM and the BCRAF, only 11.6%
      and 9.8% of women were in the "high risk" category, respectively. There was a
      positive significant correlation between the GRM and the BCRAF scores (P<0.001),
      and the BCRAF and BCRP scores (P<0.001). Factors related to high-risk perception
      were age (40-59 yr), post-menopausal phase, high-very high economic income level,
      existence of breast cancer in the family, having regular breast self-examination
      and clinical breast examination (P<0.05). CONCLUSION: In women with high risk of
      breast, cancer there is a significant difference between the women's risk
      perception and their absolute risk level.

PMID- 28435817
TI  - Molecular and Morphometrical Characterization of Fasciola Species Isolated from
      Domestic Ruminants in Ardabil Province, Northwestern Iran.
AB  - BACKGROUND: We aimed to describe morphological and morphometrical characteristics
      of Fasciola spp. in livestock from Ardabil Province, Northwest Iran. METHODS:
      Forty adult flukes were collected from different definitive hosts (cattle and
      sheep). Previously specimens were identified as F. hepatica or F. gigantica based
      on PCR-RFLP of the ITS-1 region with RsaI enzyme. We identified Fasciola spp.
      based on morphological and metric assessment of external features of fresh
      adults, morphological and metric assessment of internal anatomy of stained
      mounted worms. Statistical analysis was conducted using the Student's t-test
      implemented in SPSS 15.0 (SPSS, Chicago, Illinois). Then the morphometric
      criteria of Fasciola samples were compared with PCR-RFLP data. The results of PCR
      RFLP were confirmed by COI gene sequence. RESULTS: The differences between the
      body length, area of the body, peripheral of the body, succer area, cone length,
      cone width, in two species were significant (P < 0.05). Based on Morphological
      characterizations, 6 specimens had the intermediate morphological features and 19
      and 15 specimens had morphological features of F. hepatica and F. gigantica,
      respectively. In contrast, RFLP results showed, F. hepatica was present in 20 of
      the isolates, and F. gigantica in 20 isolates. No hybrid forms were detected.
      CONCLUSION: PCR-RFLP method can be used for differentiation of Fasciola species,
      which is more reliable method than morphology. Using morphology methods, merely,
      is not efficient for determination of genetic diversity.

PMID- 28435818
TI  - Dogmatism and Happiness.
AB  - BACKGROUND: Happiness is a drive and constructive force of life. A person feels
      wellbeing under different effective factors. Religious dogmatism that has an
      influence on the entire world is one of the depreciatory factors of happiness or
      wellbeing. The current study decided to analyze the relation between dogmatism
      and wellbeing, and according to a model, answer the following question: how does
      religious dogmatism decrease wellbeing? METHODS: This study is a correlation
      research. Population of study includes all people with 30-50 yr old who live in
      Tehran, Iran, in 2015. Among all, 180 subjects were selected as in access sample.
      The Oxford happiness questionnaire and Rokeach dogmatism scale were used. Data
      were analyzed by Pearson correlation test. RESULTS: There is a significant
      negative correlation between dogmatism and happiness (alpha=0.05). CONCLUSION:
      Dogmatism is one of the factors that have a negative effect on wellbeing.
      Religious dogmatism is the most dangerous factor against wellbeing. Dogmatic
      individuals have an inflexible cognitive system that emerges as a stable
      personality trait and decreases their adjustment with environment. Affective well
      being and cognitive wellbeing are affected by individual adjustment. Therefore,
      in dogmatic individuals with low adjustment, the decrease of affective well-being
      and cognitive wellbeing is inevitable. This process will result in decrease of
      happiness and increase of aggression.

PMID- 28435819
TI  - Psychological Disorders among Iranian Infertile Couples Undergoing Assisted
      Reproductive Technology (ART).
AB  - BACKGROUND: Worldwide, infertility affects 10%-15% of couples and most of them
      seek medical help including Assisted Reproductive Technology (ART) treatments.
      Undergoing ART treatments create many physical and emotional burdens. This study
      examined the psychological consequences of infertility in Iranian infertile males
      and females as well as their spouses, unlike previous studies that examined
      mainly females with infertility. METHODS: Subjects in this descriptive analytical
      design were recruited from the IVF Department of Mirza Koochak Khan Hospital and
      the Rouyesh Infertility Treatment Center of Tehran, Iran between Aug 2014 and Sep
      2015. Overall, 256 couples (64% response rate), consisting of 78 infertile male
      and their spouses and 50 infertile female and their spouses, were included in
      this research. The psychological disorders were measured by the Persian version
      of Symptoms Checklist-90-Revised and Cattle Inventory. RESULTS: Psychological
      disorders of infertile couples are significantly associated with increasing age,
      higher education, longer duration of infertility and unemployment (P<0.05).
      Prevalence of anxiety, depression, hypochondriasis and paranoia in infertile
      females and spouses of infertile males were significantly higher than husbands of
      infertile females (P<0.05). Obsession was more sever in infertile females was
      significantly greater than infertile males (P=0.01). Depression was significantly
      lower in infertile males than their spouses (P=0.016). CONCLUSION: Iranian
      infertile females and spouses of infertile males experienced more psychological
      disorders than infertile males and spouses of infertile females. These results
      may be due to the impact of cultural beliefs and gender roles in Iranian society.
      Anxiety, depression, obsession, paranoia and hypochondriasis should be addressed
      before any ART treatments.

PMID- 28435820
TI  - Costs of Hospital Admission on Primary Immunodeficiency Diseases.
AB  - BACKGROUND: Primary immunodeficiency diseases (PID) are heterogeneous group of
      inherited disorders mainly characterized by recurrent infections leading to
      several times hospital admissions. The economic impact of PID is a challenging
      issue; therefore, this study was designed to determine the medical costs of
      hospitalizations in this group of patients as an indicator of the direct cost of
      these diseases. METHODS: One hundred and ten children with PID hospitalized in
      the Children's Medical Center Hospital, Tehran, Iran were included in this study
      during Jan 2011 and Jan 2012. All direct costs during the admission period were
      calculated, using the hospital information system. RESULTS: Medical cost was
      7.090$ per patient per admission. Among them, about 1.580$ belong to drug
      consuming during hospitalization. Anti-infective drugs for systemic use were the
      most cost-consuming group of drugs, followed by alimentary tract and metabolism
      and blood and blood forming organs agents. Investigation of anti-infective group
      internally showed that immune sera and immunoglobulin and antiviral agents for
      systemic use consisting the most important medication for PID patients during
      hospital admission. CONCLUSION: Although the results of economic evaluations in a
      region cannot necessarily be applied to other regions, having an overall
      estimation of hospital admission costs and types of drugs used during admission
      could be helpful in health policy system.

PMID- 28435821
TI  - Utilization of PFGE as a Powerful Discriminative Tool for the Investigation of
      Genetic Diversity among MRSA Strains.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant
      challenge to the burn patient. The implementation of proper monitoring programs
      and prompt identification of epidemic MRSA strains are critical to consequently
      control and eradicate potential outbreaks. This study aimed to define the genetic
      relatedness of MRSA strains isolated from burn patients by analyzing the large
      fragments of DNA. METHODS: In this cross-sectional study, 126 pus/wound swabs
      from skin and soft tissue infections (SSTIs) were collected from inpatients of
      Shahid Motahari Burn Center (Tehran, Iran) in 2013. Then, molecular typing of
      MRSA was achieved by Pulsed-Field Gel Electrophoresis (PFGE). RESULTS: The PFGE
      analysis of MRSA indicated 31 single types and 5 common types. There was a
      significant diversity in the chromosomal digestion pattern of the MRSA strains
      explained by the acquisition of MRSA from various sources. CONCLUSION: The
      permanent import of novel types of MRSA strains despite the rigorous infection
      control measures carried out within the center. The importance of PFGE in
      understanding the epidemiology of MRSA may serve as a basis for the development
      of rational control strategies.

PMID- 28435822
TI  - Targeted Intracellular Heat Transfer in Cancer Therapy: Assessment of Asparagine
      laminated Gold Nanoparticles in Cell Model of T cell Leukemia.
AB  - BACKGROUND: High temperatures have destructive effects on cancer cells by
      damaging proteins and structures within cells. Gold nanoparticles (AuNPs) can act
      as drug delivery vehicles, especially for cancer therapy. Due to the selective
      intake of asparagine molecules into malignant cells, AuNPs were coated with
      asparagine; and CCRF-CEM human T-cell leukemia cells were treated with the new
      combination, Asn-AuNPs, at 39  degrees C. METHODS: The co-authors from a number
      of collaborative labs located at Tehran University of Medical Sciences, Tehran,
      Iran, have initiated the idea and preliminary design of this study in 2011.
      Hydroxyl surfaced AuNPs were preliminary prepared by tannin free ethanol extract
      of black tea leaves. These biogenic AuNPs were further capped with asparagines to
      form asparagine-gold nanoparticle conjugates (Asn-AuNP conjugates). Then CCRF-CEM
      human T-cell leukemia cells were separately treated with different concentrations
      of AuNPs and Asn-AuNP conjugates (3, 30, 300 MUg/mL). MTT assay and zymography
      analysis were carried out, and the apoptotic and necrotic effects of Asn-AuNPs
      were determined in comparison with AuNPs, using flow cytometry assay. RESULTS:
      Asn-AuNP conjugates at 300 MUg/mL significantly inhibited MMPs at 39  degrees C,
      compared to AuNPs. In terms of cytotoxicity, a remarkable decrease was observed
      in the percentage of viable cells treated with Asn-AuNP conjugates, rather than
      AuNPs. Moreover, the AuNPs and Asn-AuNP conjugates enhanced the level of
      apoptosis at almost similar rates. CONCLUSION: AuNPs are coated with asparagine
      molecules and the temperature is slightly increased by 2  degrees C, the
      apoptosis is not only enhanced among cells but also shifts to necrosis in higher
      concentrations of Asn-AuNP conjugates. More investigations should be carried out
      to explain the exact mechanism underlying the necrotic effects of Asn-AuNPs.

PMID- 28435823
TI  - Blood Pressure Nomograms for Children and Adolescents by Age and Body Mass Index
      in Tehran, Iran.
AB  - BACKGROUND: Normal standard references of blood pressure (BP) for children and
      adolescents should be constructed according to anthropometric indices. Therefore,
      we aimed to produce BP reference percentiles by body mass index (BMI). METHODS:
      Data on demographic characteristics, anthropometric indices and BP values of
      16246 3-18-year-old children and adolescents from 3 cross-sectional studies
      conducted in Tehran were included. To justify the need for BMI adjustment,
      quantile regression model was applied for different percentiles of systolic and
      diastolic BPs with age, sex, and the corresponding BMI percentiles. Then, Age-
      and sex-specific BP nomograms were constructed according to BMI. RESULTS: All
      regression coefficients for BMI percentiles were significant in quantile
      regression of BPs, confirming the necessity for BMI-adjusted nomograms of BP. The
      BP percentiles for each gender by age and BMI are presented. All the BP
      percentiles rose steadily in all BMI percentiles with minor discrepancies between
      the two genders. As observed, the prevalence of hypertension is estimated to be
      lower among the lean subjects and higher among overweighs when the BMI-adjusted
      BP curves are considered. CONCLUSION: The reference database constructed in this
      survey is the first Iranian BP reference by age and BMI in children and
      adolescents, from it concluded that BMI-adjusted BP curves depict a more precise
      picture of the hypertension prevalence and present a more reliable classification
      standard for hypertension.

PMID- 28435824
TI  - A Qualitative Study on Organizational Factors Affecting Occupational Accidents.
AB  - BACKGROUND: Technical, human, operational and organizational factors have been
      influencing the sequence of occupational accidents. Among them, organizational
      factors play a major role in causing occupational accidents. The aim of this
      research was to understand the Iranian safety experts' experiences and perception
      of organizational factors. METHODS: This qualitative study was conducted in 2015
      by using the content analysis technique. Data were collected through semi
      structured interviews with 17 safety experts working in Iranian universities and
      industries and analyzed with a conventional qualitative content analysis method
      using the MAXQDA software. RESULTS: Eleven organizational factors' sub-themes
      were identified: management commitment, management participation, employee
      involvement, communication, blame culture, education and training, job
      satisfaction, interpersonal relationship, supervision, continuous improvement,
      and reward system. The participants considered these factors as effective on
      occupational accidents. CONCLUSION: The mentioned 11 organizational factors are
      probably involved in occupational accidents in Iran. Naturally, improving
      organizational factors can increase the safety performance and reduce
      occupational accidents.

PMID- 28435825
TI  - Assessment of the Efficiency of Hospitals Before and After the Implementation of
      Health Sector Evolution Plan in Iran Based on Pabon Lasso Model.
AB  - BACKGROUND: Pabon Lasso model was applied to assess the relative performance of
      hospitals affiliated to Kurdistan University of Medical Sciences (KUMS) before
      and after the implementation of Health Sector Evolution Plan (HSEP) in Iran.
      METHODS: This cross-sectional study was carried out in 11 public hospitals
      affiliated to KUMS in 2015. Twelve months before and after the implementation of
      the first phase of HSEP, a checklist was used to collect data from computerized
      databases within the hospitals' admission and discharge units. Pabon Lasso model
      includes three indices: bed turnover, bed occupancy ratio, and average length of
      stay. RESULTS: Analysis of hospital performance showed an increase in mean of bed
      occupancy and turnover ratio, which changed from 65.40% and 86.22 times/year
      during 12 months before to 69.97% and 90.98 times/year during 12 months after
      HSEP, respectively. In line with Pabon Lasso model, before the implementation of
      HSEP, 27.27% and 36.36% of the hospitals were entirely efficient and inefficient,
      respectively, whilst after the implementation of HSEP, their condition changed to
      18.18% and 27.27%, in order. CONCLUSION: Indicators of bed occupancy and turnover
      ratio had a 4% increase in the studied hospitals after the implementation of
      HSEP. Number of the hospitals in the efficient zone reduced because of the
      relative measurement of efficiency by Pabon Lasso model. Since more than 50% of
      the hospitals in the studied province have not yet reached their optimal bed
      occupancy ratio (more than 70%), short-term and suitable strategy for improving
      the efficiency is to stop further expansion of hospitals as well as developing
      the number of hospital beds.

PMID- 28435826
TI  - Climate Change and Simulation of Cardiovascular Disease Mortality: A Case Study
      of Mashhad, Iran.
AB  - BACKGROUND: Weather and climate play a significant role in human health. We are
      accustomed to affects the weather conditions. By increasing or decreasing the
      environment temperature or change of seasons, some diseases become prevalent or
      remove. This study investigated the role of temperature in cardiovascular disease
      mortality of city of Mashhad in the current decade and its simulation in the
      future decades under conditions of climate change. METHODS: Cardiovascular
      disease mortality data and the daily temperatures data were used during (2004
      2013) period. First, the correlation between cardiovascular disease mortality and
      maximum and minimum temperatures were calculated then by using General
      Circulation Model, Emissions Scenarios, and temperature data were extracted for
      the next five decades and finally, mortality was simulated. RESULTS: There is a
      strong positive association between maximum temperature and mortality (r= 0.83, P
      value<0.01), also observed a negative and weak but significant association
      between minimum temperatures and mortality. The results obtained from simulation
      show increased temperature in the next decades in Mashhad and a 1  degrees C
      increase in maximum temperature is associated with a 4.27% (95%CI: 0.91, 7.00)
      increase in Cardiovascular disease mortality. CONCLUSION: By increasing
      temperature and the number of hot days the cardiovascular disease mortality
      increases and these increases will be intensified in the future decades.
      Therefore, necessary preventive measures are required to mitigate temperature
      effects with greater attention to vulnerable group.

PMID- 28435827
TI  - Prevalence of Hepatitis C Virus Infection in General Population of Mashhad,
      Northeastern Iran.
AB  - BACKGROUND: Hepatitis C Virus (HCV) infection is one of the major blood-borne
      infections worldwide. HCV carriers may develop chronic hepatitis leading to liver
      cirrhosis and hepatocellular carcinoma (HCC). There is no overall estimate of the
      infection prevalence in the northeast of Iran. We have performed this research in
      order to determine accurately the prevalence and risk factors of HCV infection
      among general population in Mashhad. METHODS: During 2009, 1678 people between 1
      to 90 yr old with the mean age of 29.1+/-18.5 yr were selected randomly by
      multistage sampling from different geographical regions of the city proportionate
      to sex and age distribution of population in 2006 census. ELISA was used to
      screen for antibodies and RT-PCR tested the positive samples. RESULTS: HCV
      infection was detected in 7/1654 cases; overall prevalence of the infection was
      0.42% (95%CI: 0.17-0.87%), 0.80% and 0.11% among males and females, respectively
      (P= 0.051). One HCV-infected subject was also positive for hepatitis B surface
      antigen (HBsAg), however, no cases showed HIV or HTLV seropositivity. CONCLUSION:
      In comparison with similar studies, the prevalence of HCV infection in Mashhad is
      low.

PMID- 28435828
TI  - Malnutrition in Early Life, Socio-demographic and Self-reported Appetite in
      Adulthood in Chongqing, China.

PMID- 28435829
TI  - Physiological Index, Weight Control Behavior, and Quality of Life Related to
      Obesity-related Metabolic Syndrome in Korean Adults.

PMID- 28435830
TI  - High Socioeconomic Status and Key Risk Factors of Overweight and Obesity among
      Rural-to-Urban Migrant 7-10y-old Children in Shanghai, China.

PMID- 28435831
TI  - Health-related Quality of Life and Related Factors among Rural Residents in
      Cambodia.

PMID- 28435832
TI  - Microbiological Biosafety, Multiple Drug Resistance and Functional Diversity of
      Bacteria Associated with the Surfaces of Raw Vegetables.

PMID- 28435833
TI  - Diet in Acne Vulgaris: Open or Solved Problem?

PMID- 28435834
TI  - Prevalence of HIV in a Prison of Tehran by Active Case Finding.

PMID- 28435835
TI  - The Role of Project Management Office in Public Health: A New Approach for
      Establishment in Iran.

PMID- 28435836
TI  - The Comparative Diagnostic Features of Canine and Human Lymphoma.
AB  - The non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid
      malignancies that are among the most common neoplasms of both dogs and humans.
      Owing to shared molecular, signaling, incidence, and pathologic features, there
      is a strong framework supporting the utilization of canine lymphoma as a
      comparative, large animal model of human NHL. In alignment with the biologic
      similarities, the current approach towards the diagnosis and classification of
      canine lymphoma is based upon the human World Health Organization guidelines.
      While this approach has contributed to an increasing appreciation of the
      potential biological scope of canine lymphoma, it has also become apparent that
      the most appropriate diagnostic philosophy must be multimodal, namely by
      requiring knowledge of microscopic, immunophenotypic, and clinical features
      before establishing a final disease diagnosis. This review seeks to illustrate
      the comparative similarities and differences in the diagnosis of canine lymphoma
      through the presentation of the microscopic and immunophenotypic features of its
      most common forms.

PMID- 28435837
TI  - Staphylococcus aureus type I signal peptidase: essential or not essential, that's
      the question.
AB  - Secretion of proteins into the extracellular environment is crucial for the
      normal physiology and virulence of pathogenic bacteria. Type I signal peptidase
      (SPase I) mediates the final step of bacterial secretion, by cleaving proteins at
      their signal peptide once they are translocated by the Sec or twin-arginine (Tat)
      translocon. SPase I has long been thought to be essential for viability in
      multiple bacterial pathogens. Challenging this view, we and others have recently
      created Staphylococcus aureus bacteria lacking the SPase I SpsB that are viable
      and able to grow in vitro when over-expressing a native gene cassette encoding
      for a putative ABC transporter. This transporter apparently compensates for
      SpsB's essential function by mediating alternative cleavage of a subset of
      proteins at a site distinct from the SpsB-cleavage site, leading to SpsB
      independent secretion. This alternative secretion system also drives the main
      mechanism of resistance to an arylomycin-derived SpsB inhibitor, by means of
      mutations in a putative transcriptional repressor (cro/cI) causing over
      expression of the ABC transporter. These findings raise multiple interesting
      biological questions. Unraveling the mechanism of SpsB-independent secretion may
      provide an interesting twist to the paradigm of bacterial secretion.

PMID- 28435838
TI  - Thiol trapping and metabolic redistribution of sulfur metabolites enable cells to
      overcome cysteine overload.
AB  - Cysteine is an essential requirement in living organisms. However, due to its
      reactive thiol side chain, elevated levels of intracellular cysteine can be toxic
      and therefore need to be rapidly eliminated from the cellular milieu. In mammals
      and many other organisms, excess cysteine is believed to be primarily eliminated
      by the cysteine dioxygenase dependent oxidative degradation of cysteine, followed
      by the removal of the oxidative products. However, other mechanisms of tackling
      excess cysteine are also likely to exist, but have not thus far been explored. In
      this study, we use Saccharomyces cerevisiae, which naturally lacks a cysteine
      dioxygenase, to investigate mechanisms for tackling cysteine overload.
      Overexpressing the high affinity cysteine transporter, YCT1, enabled yeast cells
      to rapidly accumulate high levels of intracellular cysteine. Using targeted
      metabolite analysis, we observe that cysteine is initially rapidly interconverted
      to non-reactive cystine in vivo. A time course revealed that cells systematically
      convert excess cysteine to inert thiol forms; initially to cystine, and
      subsequently to cystathionine, S-Adenosyl-L-homocysteine (SAH) and S-Adenosyl L
      methionine (SAM), in addition to eventually accumulating glutathione (GSH) and
      polyamines. Microarray based gene expression studies revealed the upregulation of
      arginine/ornithine biosynthesis a few hours after the cysteine overload, and
      suggest that the non-toxic, non-reactive thiol based metabolic products are
      eventually utilized for amino acid and polyamine biogenesis, thereby enabling
      cell growth. Thus, cells can handle potentially toxic amounts of cysteine by a
      combination of thiol trapping, metabolic redistribution to non-reactive thiols
      and subsequent consumption for anabolism.

PMID- 28435839
TI  - The frequency of yeast [PSI+] prion formation is increased during chronological
      ageing.
AB  - Ageing involves a time-dependent decline in a variety of intracellular mechanisms
      and is associated with cellular senescence. This can be exacerbated by prion
      diseases which can occur in a sporadic manner, predominantly during the later
      stages of life. Prions are infectious, self-templating proteins responsible for
      several neurodegenerative diseases in mammals and several prion-forming proteins
      have been found in yeast. We show here that the frequency of formation of the
      yeast [PSI+ ] prion, which is the altered form of the Sup35 translation
      termination factor, is increased during chronological ageing. This increase is
      exacerbated in an atg1 mutant suggesting that autophagy normally acts to suppress
      age-related prion formation. We further show that cells which have switched to
      [PSI+ ] have improved viability during chronological ageing which requires active
      autophagy. [PSI+ ] stains show increased autophagic flux which correlates with
      increased viability and decreased levels of cellular protein aggregation. Taken
      together, our data indicate that the frequency of [PSI+ ] prion formation
      increases during yeast chronological ageing, and switching to the [PSI+ ] form
      can exert beneficial effects via the promotion of autophagic flux.

PMID- 28435840
TI  - Microbial flora, probiotics, Bacillus subtilis and the search for a long and
      healthy human longevity.
AB  - Probiotics are live microorganisms that have beneficial effects on host health,
      including extended lifespan, when they are administered or present in adequate
      quantities. However, the mechanisms by which probiotics stimulate host longevity
      remain unclear and very poorly understood. In a recent study (Nat. Commun. 8,
      14332 (2017) doi: 10.1038/ncomms14332), we used the spore-forming probiotic
      bacterium Bacillus subtilis and the model organism Caenorhabditis elegans to
      study the mechanism by which a probiotic bacterium affects host longevity. We
      found that biofilm-proficient B. subtilis colonized the C. elegans gut and
      extended the worm lifespan significantly longer than did biofilm-deficient
      isogenic strains. In addition to biofilm proficiency, the quorum-sensing
      pentapeptide CSF and nitric oxide (NO) represent the entire B. subtilis
      repertoire responsible for the extended longevity of C. elegans. B. subtilis
      grown under biofilm-supporting conditions synthesized higher levels of NO and CSF
      than under planktonic growth conditions, emphasizing the key role of the biofilm
      in slowing host aging. Significantly, the prolongevity effect of B. subtilis was
      primarily due to a downregulation of the insulin-like signaling system that
      precisely is a key partaker in the healthy longevity of human centenarians. These
      findings open the possibility to test if the regular consumption of B. subtilis
      incorporated in foods and beverages could significantly extend human life
      expectancy and contribute to stop the development of age-related diseases.

PMID- 28435841
TI  - Evading plant immunity: feedback control of the T3SS in Pseudomonas syringae.
AB  - Microbes are responsible for over 10% of the global yield losses in staple crops
      such as wheat, rice, and maize. Understanding the decision-making strategies that
      enable bacterial plant pathogens to evade the host immune system and cause
      disease is essential for managing their ever growing threat to food security.
      Many utilise the needle-like type III secretion system (T3SS) to suppress plant
      immunity, by injecting effector proteins that inhibit eukaryotic signalling
      pathways into the host cell cytoplasm. Plants can in turn evolve resistance to
      specific pathogens via recognition and blocking of the T3SS effectors, so leading
      to an ongoing co-evolutionary 'arms race' between pathogen and host pairs. The
      extracytoplasmic function sigma factor HrpL co-ordinates the expression of the
      T3SS regulon in the leaf-dwelling Pseudomonas syringae and similar pathogens.
      Recently, we showed that association of HrpL with a target promoter directly
      adjacent to the hrpL gene imposes negative autogenous control on its own
      expression level due to overlapping regulatory elements. Our results suggest that
      by down-regulating T3SS function, this fine-tuning mechanism enables P. syringae
      to minimise effector-mediated elicitation of plant immunity.

PMID- 28435842
TI  - Is individual smoking behaviour influenced by area-level ethnic density? A cross
      sectional electronic health database study of inner south-east London.
AB  - Tobacco smoking remains one of the greatest public health problems facing the UK
      today. It varies significantly by ethnic group. This study aimed to determine
      whether ethnic differences in smoking behaviour are related to neighbourhood
      level, own-group ethnic density across south and east London. The association
      between ethnic density and individual smoking behaviour was assessed by
      multilevel logistic regression using the electronic health records of 688 397
      general practitioner-registered patients. Restricted cubic splines were created
      to explore whether the effect of ethnic density on smoking behaviour was
      nonlinear. Increasing own-group ethnic density was found to be associated with a
      significant reduction in the odds of being a current smoker in all ethnic groups,
      except for Black Caribbean women. The relationship between ethnic density and
      current smoking was found to be nonlinear, with the strength of association
      varying significantly by sex and ethnic group. These novel findings point to a
      complex relationship between culture, neighbourhood-level experience of adversity
      or social support and smoking behaviour, and will allow us to target smoking
      cessation services differentially to individuals/groups living in relative ethnic
      isolation, who do not benefit from the potential cultural/social factors
      associated with reduced tobacco consumption.

PMID- 28435843
TI  - MMP-7 is a predictive biomarker of disease progression in patients with
      idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease
      with poor prognosis, which is characterised by destruction of normal lung
      architecture and excessive deposition of lung extracellular matrix. The
      heterogeneity of disease progression in patients with IPF poses significant
      obstacles to patient care and prevents efficient development of novel therapeutic
      interventions. Blood biomarkers, reflecting pathobiological processes in the
      lung, could provide objective evidence of the underlying disease. Longitudinally
      collected serum samples from the Bosentan Use in Interstitial Lung Disease
      (BUILD)-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP
      7), Fas death receptor ligand, osteopontin and procollagen type I C-peptide), to
      assess their potential prognostic capabilities and to follow changes during
      disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7
      showed clearly elevated protein levels compared with samples from healthy
      controls, and further investigations demonstrated that MMP-7 levels also
      increased over time. Baseline levels of MMP-7 were able to predict patients who
      had higher risk of worsening and, notably, baseline levels of MMP-7 could predict
      changes in FVC as early as month 4. MMP-7 shows potential to be a reliable
      predictor of lung function decline and disease progression.

PMID- 28435844
TI  - Clustering network layers with the strata multilayer stochastic block model.
AB  - Multilayer networks are a useful data structure for simultaneously capturing
      multiple types of relationships between a set of nodes. In such networks, each
      relational definition gives rise to a layer. While each layer provides its own
      set of information, community structure across layers can be collectively
      utilized to discover and quantify underlying relational patterns between nodes.
      To concisely extract information from a multilayer network, we propose to
      identify and combine sets of layers with meaningful similarities in community
      structure. In this paper, we describe the "strata multilayer stochastic block
      model" (sMLSBM), a probabilistic model for multilayer community structure. The
      central extension of the model is that there exist groups of layers, called
      "strata", which are defined such that all layers in a given stratum have
      community structure described by a common stochastic block model (SBM). That is,
      layers in a stratum exhibit similar node-to-community assignments and SBM
      probability parameters. Fitting the sMLSBM to a multilayer network provides a
      joint clustering that yields node-to-community and layer-to-stratum assignments,
      which cooperatively aid one another during inference. We describe an algorithm
      for separating layers into their appropriate strata and an inference technique
      for estimating the SBM parameters for each stratum. We demonstrate our method
      using synthetic networks and a multilayer network inferred from data collected in
      the Human Microbiome Project.

PMID- 28435845
TI  - A Novel ASK Inhibitor AGI-1067 Inhibits TLR-4-Mediated Activation of ASK1 by
      Preventing Dissociation of Thioredoxin from ASK1.
AB  - The cell type that normally limits the inflammatory and atherosclerotic process
      is the vascular endothelial cell (EC) that can be regulated by proinflammatory
      and various stresses. Toll-like receptor-4 (TLR4) plays an important role in the
      pathogenesis of atherosclerosis, in part, by activating apoptosis signal
      regulating kinase 1 (ASK1) to initiate the activation of MAP kinases pathways and
      the expression of inflammatory genes. In the present study, we test the
      hypothesis that AGI-1067 acts as an anti-inflammatory agent by inhibiting the
      activation of ASK1 in human EC. Pretreatment of human aortic endothelial cells
      with AGI-1067 inhibits TLR4 ligand (LPS)-induced activation of ASK1 and the
      downstream p38 and c-Jun N-terminal kinase (JNK) MAP kinases. LPS dissociates two
      endogenous inhibitors thioredoxin-1 (Trx1) and 14-3-3 from ASK1, leading to ASK1
      autoactivation. Interestingly, AGI-1067 inhibits the dissociation of Trx1, but
      not 14-3-3, from ASK1. However, inhibition of Trx1 dissociation from ASK1 by AGI
      1067 is sufficient to suppress LPS-mediated phosphorylation of the transcription
      factors c-Jun and activating transcription factor 2, and inhibit LPS-induced
      inflammatory genes including vascular cell adhesion molecule 1, E-selectin, IL-6
      and monocyte chemoattractant protein 1. Our findings suggest that AGI-1067 as a
      unique ASK1 inhibitor to inhibit TLR4-mediated ASK1 activation, contributing to
      its anti-inflammatory properties.

PMID- 28435846
TI  - Psychometric Properties and Characteristics of the North-East Visual
      Hallucinations Interview in Parkinson's Disease.
AB  - BACKGROUND: Visual Hallucinations (VH) are a common symptom experienced by
      individuals with Parkinson's disease (PD); however, a validated measure of VH has
      yet to be established for this population. The North-East Visual Hallucinations
      Interview (NEVHI), a promising VH measure, has not been well validated in PD. The
      aim of this study was to evaluate the convergent and discriminant validity of the
      NEVHI as well as the proportional identification and characteristics of VH in PD.
      METHODS: One hundred seventeen individuals with PD completed the NEVHI as well as
      evaluations of psychological, cognitive, motor, and visual functioning as
      measures of convergent and divergent validity. The hallucination items from the
      Neuropsychiatric Inventory (NPI) and the Movement Disorder Society-sponsored
      revision of the Unified Parkinson's Disease Scale (MDS-UPDRS) were used to assess
      convergent validity. RESULTS: The NEVHI identified 20.5% of PD patients with VH,
      which consisted of all individuals detected by the MDS-UPDRS and NPI and nine
      additional individuals not detected by the other measures. The NEVHI was strongly
      correlated with the MDS-UPDRS hallucinations item, and weakly correlated with the
      NPI VH item. Weak to non-significant correlations were found between the NEVHI
      and measures of psychological, cognitive, motor, visual, and demographic
      characteristics. DISCUSSION: The NEVHI identified a greater number of individuals
      with VH than either the MDS-UPDRS or NPI. Results demonstrated good convergent
      validity between the NEVHI and a clinician-administered-to-patient-report measure
      of VH and excellent divergent validity, supporting the NEVHI as a valid and
      preferable measure for assessing the presence of VH in PD.

PMID- 28435847
TI  - Stroke 1-2-0: The strategy and video release.

PMID- 28435848
TI  - Multiple Levels of Influence That Impact Youth Tobacco Use.
AB  - OBJECTIVE: Multiple levels of influence interplay to impact youth tobacco use. We
      work towards understanding important policy and environmental strategies that are
      associated with youth tobacco use behaviors. METHODS: We utilized data from
      participants of the Monitoring the Future (MTF) study and linked national data
      from multiple sources to assess correlates of youth tobacco use behaviors across
      individual, family, school, community, and state-level policy influences.
      RESULTS: Higher cigarette prices had the strongest association with youth tobacco
      use behaviors. Demographic and socio-economic characteristics at the individual,
      familial, and community/school-levels were associated with youth tobacco use
      behaviors. CONCLUSIONS: In the present study, we confirm that higher cigarette
      prices could help to reduce youth tobacco use behaviors. Several states are still
      lagging behind in terms of their low cigarette tax and they should enact tax
      policies to reduce youth tobacco use.

PMID- 28435849
TI  - Effects of cyclic compression on the mechanical properties and calcification
      process of immature chick bone tissue in culture.
AB  - Contribution of mechanical loading to tissue growth during both the development
      and post-natal maturation is of a particular interest, as its understanding would
      be important to strategies in bone tissue engineering and regenerative medicine.
      The present study has been performed to investigate how immature bone responds to
      mechanical loading using an ex vivo culture system. A slice of the tibia, with
      the thickness of 3 mm, was obtained from 0-day-old chick. For the ex vivo culture
      experiment in conjunction with cyclic compressive loading, we developed a custom
      made, bioreactor system where both the load and the deformation applied to the
      specimen was recorded. Cyclic compression, with an amplitude of 0.3 N
      corresponding to 1 to 2% compressive strain, was applied to immature bone
      specimen during a 3-day culture period at an overall loading rate 3-4 cycles/min,
      in the presence of beta-glycerol phosphate and dexamethasone in culture medium.
      The stress-strain relationship was obtained at the beginning and the end of the
      culture experiment. In addition, analyses for alkaline phosphate release, cell
      viability and tissue calcification were also performed. It was exhibited that
      elastic moduli of bone slices were significantly elevated at the end of the 3-day
      culture in the presence of cyclic compression, which was a similar phenomenon to
      significant elevation of the elastic moduli of bone tissue by the maturation from
      0-day old to 3-day old. By contrast, no significant changes in the moduli were
      observed in the absence of cyclic compression or in deactivated, cell-free
      samples. The increases in the moduli were coincided with the increase in
      calcified area in the bone samples. It was confirmed that immature bone can
      respond to compressive loading in vitro and demonstrate the growth of bone
      matrix, similar to natural, in vivo maturation. The elevation of the elastic
      moduli was attributable to the increased calcified area and the realignment of
      collagen fibers parallel to the loading direction. The ex vivo loading system
      established here can be further applied to study responses to mechanical loading
      in osteogenesis as well as callus maturation for better understanding of factors
      to consider in successful bone regeneration with mechanical factors.

PMID- 28435850
TI  - Paraneoplastic myositis secondary to poorly differentiated serous carcinoma of
      ovarian/tubal origin.
AB  - *Ovarian cancer can present as paraneoplastic myositis.*Presented with
      progressive weakness unresponsive to treatment with glucocorticoids*Imaging
      revealed bilateral ovarian masses, myositis resolved after surgery.*Ovarian
      cancer should be included on the differential diagnosis of a patient presenting
      with myositis.

PMID- 28435851
TI  - Choroidal thinning: Alzheimer's disease and aging.
AB  - INTRODUCTION: The purpose of this study was to measure and to compare macular
      choroidal thickness (CT) between patients with mild Alzheimer's disease (AD),
      patients without AD, and elderly patients. METHODS: CT was measured manually in
      13 locations at 500-MUm intervals of a horizontal and a vertical section from the
      fovea. Linear regression models were used to analyze the data. RESULTS: Fifty
      patients with a diagnosis of mild AD (73.1 years), 152 patients without AD (71.03
      years), and 50 elderly without AD (82.14 years) were included. In the AD
      patients, CT was significantly thinner in all 13 locations (P < .001-comparing
      with age-match group), and comparing with the elderly group, a more pronounced
      difference was found in two locations temporal to the fovea. DISCUSSION: Patients
      with AD showed a significant choroidal thinning even when compared with elderly
      subjects. The reduction of CT may aid in the diagnoses of AD, probably reflecting
      the importance of vascular factors in their pathogenesis.

PMID- 28435852
TI  - Changes in metabolic risk factors over 10 years and their associations with late
      life cognitive performance: The Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: We examined whether changes in metabolic factors over 10 years were
      associated with cognitive performance. METHODS: Participants from the Multi
      Ethnic Study of Atherosclerosis were followed since baseline (2000-2002) with
      five clinical examinations. At exam 5 (2010-2012), they received a short
      cognitive battery (Cognitive Abilities Screening Instrument [CASI], Digit Symbol
      Coding [DSC], and Digit Span [DS]). We examined associations between baseline
      metabolic factors and their changes over time before cognitive testing. RESULTS:
      Among 4392 participants, baseline metabolic disorders (fasting glucose, systolic
      and diastolic blood pressures) were significantly associated with poorer CASI,
      DSC, and DS scores measured 10 years later. Increases in blood pressure were
      associated with lower cognitive performance. Results did not differ by
      race/ethnicity and were stronger among those without the APOE epsilon4 allele.
      CONCLUSIONS: Cognitive performance was associated with antecedent abnormalities
      in glucose metabolism and blood pressure increases. Findings appeared stronger
      among APOE epsilon4-negative participants.

PMID- 28435854
TI  - A Clinical Trial Simulation Evaluating Epinephrine Pharmacokinetics at various
      Dosing Frequencies during Cardiopulmonary Resuscitation.
AB  - OBJECTIVE: This article seeks to test the hypothesis that repeated 1mg
      intravenous epinephrine dosing intervals of 3-minutes and 5-minutes results in
      differences in the total drug exposure and the maximum epinephrine concentration
      using simulated cardiopulmonary resuscitation (CPR) dosing. METHODS: Published
      population pharmacokinetic parameters were identified in the literature and
      pharmacokinetic dosing simulations were conducted according to the 2015 American
      Heart Association guidelines for CPR in adults. The stochastic pharmacokinetic
      simulations were conducted in MATLAB and R for statistical programming. RESULTS:
      A total of 5000 simulations were conducted in MATLAB while 90,000 data points for
      the 3-minute dosing interval and 150,000 data points for the 5-minute epinephrine
      dosing interval resulted from pharmacokinetic simulations in R. The difference
      between the 3-minute and 5-minute dosing intervals for patients with a SAP score
      of 30, were found to be: Male DeltaAUC=2416 and DeltaCmax=71, Female
      DeltaAUC=1422 and DeltaCmax=41, and for a 70kg patient DeltaAUC=2968 and
      DeltaCmax=90. While in virtual healthy participants, the differences were
      calculated to be DeltaAUC=2658 and DeltaCmax=81 for 3-minute and 5-minute dosing
      frequencies. CONCLUSIONS: Epinephrine plasma levels during a simulated CPR
      scenario in a virtual patient population are dependent upon intravenous dosing
      intervals of either 3-minutes or 5-minutes. Based on the results of this clinical
      trial simulation, implications may exist that may require clinical studies
      investigating the influence of the 1mg epinephrine dosing frequency on the return
      of spontaneous circulation.

PMID- 28435853
TI  - Preclinical Alzheimer's disease and longitudinal driving decline.
AB  - INTRODUCTION: Links between preclinical AD and driving difficulty onset would
      support the use of driving performance as an outcome in primary and secondary
      prevention trials among older adults (OAs). We examined whether AD biomarkers
      predicted the onset of driving difficulties among OAs. METHODS: 104 OAs (65+
      years) with normal cognition took part in biomarker measurements, a road test,
      clinical and psychometric batteries and self-reported their driving habits.
      RESULTS: Higher values of CSF tau/Abeta42 and ptau181/Abeta42 ratios, but not
      uptake on PIB amyloid imaging (p=.12), predicted time to a rating of Marginal or
      Fail on the driving test using Cox proportional hazards models. Hazards ratios
      (95% confidence interval) were 5.75 (1.70-19.53), p=.005 for CSF tau/Abeta42;
      6.19 (1.75-21.88) and p=.005 for CSF ptau181/Abeta42. DISCUSSION: Preclinical AD
      predicted time to receiving a Marginal or Fail rating on an on-road driving test.
      Driving performance shows promise as a functional outcome in AD prevention
      trials.

PMID- 28435855
TI  - First clinical experiences with a novel endoscopic over-the-scope clip system.
AB  - We describe our experience with a new over-the-scope clip (OTSC) system (Padlock
      Clip?) in the treatment of 14 patients. Eight of the 14 patients were treated for
      closure of gastrointestinal fistulas (n?=?4), iatrogenic gastrointestinal
      perforations (n?=?2), or hemostasis of post-polypectomy bleeding (n?=?2). The
      site of clipping was the lower gastrointestinal tract in five patients and the
      upper gastrointestinal tract in three patients. The clip was successfully
      delivered in seven out of the eight patients and clinical success was achieved in
      all patients. Endoscopic full thickness resection (EFTR) was performed to treat
      six patients: four with recurrent adenoma (n?=?4), one with ulcerated nodules at
      ileorectal anastomosis, and one with a neuro-endocrine tumor of the rectum. A
      complete intestinal wall resection was achieved in three of the six patients
      (50?%) and an R0 resection in five of the six patients (83.3?%). No complications
      related to the procedure and no recurrence at endoscopic follow-up were observed
      in any patient. The novel Padlock Clip seems to be an effective and safe tool to
      treat gastrointestinal fistulas, perforations or post-polypectomy bleeding, and
      to perform EFTR.

PMID- 28435857
TI  - Dominant 100,000-year precipitation cyclicity in a late Miocene lake from
      northeast Tibet.
AB  - East Asian summer monsoon (EASM) precipitation received by northern China over
      the past 800 thousand years (ky) is characterized by dominant 100-ky periodicity,
      mainly attributed to CO2 and Northern Hemisphere insolation-driven ice sheet
      forcing. We established an EASM record in the Late Miocene from lacustrine
      sediments in the Qaidam Basin, northern China, which appears to exhibit a
      dominant 100-ky periodicity similar to the EASM records during the Late
      Quaternary. Because evidence suggests that partial or ephemeral ice existed in
      the Northern Hemisphere during the Late Miocene, we attribute the 100-ky cycles
      to CO2 and Southern Hemisphere insolation-driven Antarctic ice sheet forcing.
      This indicates a >6-million year earlier onset of the dominant 100-ky Asian
      monsoon and, likely, glacial and CO2 cycles and may indicate dominant forcing of
      Northern Hemisphere climate by CO2 and Southern Hemisphere ice sheets in a warm
      world.

PMID- 28435856
TI  - Dynamic microbiome evolution in social bees.
AB  - The highly social (eusocial) corbiculate bees, comprising the honey bees, bumble
      bees, and stingless bees, are ubiquitous insect pollinators that fulfill critical
      roles in ecosystem services and human agriculture. Here, we conduct wide sampling
      across the phylogeny of these corbiculate bees and reveal a dynamic evolutionary
      history behind their microbiota, marked by multiple gains and losses of gut
      associates, the presence of generalist as well as host-specific strains, and
      patterns of diversification driven, in part, by host ecology (for example, colony
      size). Across four continents, we found that different host species have distinct
      gut communities, largely independent of geography or sympatry. Nonetheless, their
      microbiota has a shared heritage: The emergence of the eusocial corbiculate bees
      from solitary ancestors appears to coincide with the acquisition of five core gut
      bacterial lineages, supporting the hypothesis that host sociality facilitates the
      development and maintenance of specialized microbiomes.

PMID- 28435858
TI  - Flexible and stretchable nanowire-coated fibers for optoelectronic probing of
      spinal cord circuits.
AB  - Studies of neural pathways that contribute to loss and recovery of function
      following paralyzing spinal cord injury require devices for modulating and
      recording electrophysiological activity in specific neurons. These devices must
      be sufficiently flexible to match the low elastic modulus of neural tissue and to
      withstand repeated strains experienced by the spinal cord during normal movement.
      We report flexible, stretchable probes consisting of thermally drawn polymer
      fibers coated with micrometer-thick conductive meshes of silver nanowires. These
      hybrid probes maintain low optical transmission losses in the visible range and
      impedance suitable for extracellular recording under strains exceeding those
      occurring in mammalian spinal cords. Evaluation in freely moving mice confirms
      the ability of these probes to record endogenous electrophysiological activity in
      the spinal cord. Simultaneous stimulation and recording is demonstrated in
      transgenic mice expressing channelrhodopsin 2, where optical excitation evokes
      electromyographic activity and hindlimb movement correlated to local field
      potentials measured in the spinal cord.

PMID- 28435859
TI  - The frequency and extent of sub-ice phytoplankton blooms in the Arctic Ocean.
AB  - In July 2011, the observation of a massive phytoplankton bloom underneath a sea
      ice-covered region of the Chukchi Sea shifted the scientific consensus that
      regions of the Arctic Ocean covered by sea ice were inhospitable to
      photosynthetic life. Although the impact of widespread phytoplankton blooms under
      sea ice on Arctic Ocean ecology and carbon fixation is potentially marked, the
      prevalence of these events in the modern Arctic and in the recent past is, to
      date, unknown. We investigate the timing, frequency, and evolution of these
      events over the past 30 years. Although sea ice strongly attenuates solar
      radiation, it has thinned significantly over the past 30 years. The thinner
      summertime Arctic sea ice is increasingly covered in melt ponds, which permit
      more light penetration than bare or snow-covered ice. Our model results indicate
      that the recent thinning of Arctic sea ice is the main cause of a marked increase
      in the prevalence of light conditions conducive to sub-ice blooms. We find that
      as little as 20 years ago, the conditions required for sub-ice blooms may have
      been uncommon, but their frequency has increased to the point that nearly 30% of
      the ice-covered Arctic Ocean in July permits sub-ice blooms. Recent climate
      change may have markedly altered the ecology of the Arctic Ocean.

PMID- 28435860
TI  - Onymity promotes cooperation in social dilemma experiments.
AB  - One of the most elusive scientific challenges for over 150 years has been to
      explain why cooperation survives despite being a seemingly inferior strategy from
      an evolutionary point of view. Over the years, various theoretical scenarios
      aimed at solving the evolutionary puzzle of cooperation have been proposed,
      eventually identifying several cooperation-promoting mechanisms: kin selection,
      direct reciprocity, indirect reciprocity, network reciprocity, and group
      selection. We report the results of repeated Prisoner's Dilemma experiments with
      anonymous and onymous pairwise interactions among individuals. We find that
      onymity significantly increases the frequency of cooperation and the median
      payoff per round relative to anonymity. Furthermore, we also show that the
      correlation between players' ranks and the usage of strategies (cooperation,
      defection, or punishment) underwent a fundamental shift, whereby more prosocial
      actions are rewarded with a better ranking under onymity. Our findings prove that
      reducing anonymity is a valid promoter of cooperation, leading to higher payoffs
      for cooperators and thus suppressing an incentive-anonymity-that would ultimately
      favor defection.

PMID- 28435862
TI  - Financialization impedes climate change mitigation: Evidence from the early
      American solar industry.
AB  - The article investigates how financialization impedes climate change mitigation
      by examining its effects on the early history of one low-carbon industry, solar
      photovoltaics in the United States. The industry grew rapidly in the 1970s, as
      large financial conglomerates acquired independent firms. While providing needed
      financial support, conglomerates changed the focus from existing markets in
      consumer applications toward a future utility market that never materialized.
      Concentration of the industry also left it vulnerable to the corporate
      restructuring of the 1980s, when the conglomerates were dismantled and solar
      divisions were pared back or sold off to foreign firms. Both the move toward
      conglomeration, when corporations became managed as stock portfolios, and its
      subsequent reversal were the result of increased financial dominance over
      corporate governance. The American case is contrasted with the more successful
      case of Japan, where these changes to corporate governance did not occur.
      Insulated from shareholder pressure and financial turbulence, Japanese
      photovoltaics manufacturers continued to expand investment throughout the 1980s
      when their American rivals were cutting back. The study is informed by Joseph
      Schumpeter's theory of creative destruction and Hyman Minsky's theory of
      financialization, along with economic sociology. By highlighting the tenuous and
      conflicting relation between finance and production that shaped the early history
      of the photovoltaics industry, the article raises doubts about the prevailing
      approach to mitigate climate change through carbon pricing. Given the uncertainty
      of innovation and the ease of speculation, it will do little to spur low-carbon
      technology development without financial structures supporting patient capital.

PMID- 28435861
TI  - Origin of an ancient hormone/receptor couple revealed by resurrection of an
      ancestral estrogen.
AB  - The origin of ancient ligand/receptor couples is often analyzed via
      reconstruction of ancient receptors and, when ligands are products of metabolic
      pathways, they are not supposed to evolve. However, because metabolic pathways
      are inherited by descent with modification, their structure can be compared using
      cladistic analysis. Using this approach, we studied the evolution of steroid
      hormones. We show that side-chain cleavage is common to most vertebrate steroids,
      whereas aromatization was co-opted for estrogen synthesis from a more ancient
      pathway. The ancestral products of aromatic activity were aromatized steroids
      with a side chain, which we named "paraestrols." We synthesized paraestrol A and
      show that it effectively binds and activates the ancestral steroid receptor. Our
      study opens the way to comparative studies of biologically active small
      molecules.

PMID- 28435863
TI  - Bulk layered heterojunction as an efficient electrocatalyst for hydrogen
      evolution.
AB  - We describe the spontaneous formation of composite chalcogenide materials that
      consist of two-dimensional (2D) materials dispersed in bulk and their unusual
      charge transport properties for application in hydrogen evolution reactions
      (HERs). When MoS2 as a representative 2D material is deposited on transition
      metals (such as Cu) in a controlled manner, the sulfidation reactions also occur
      with the metal. This process results in remarkably unique structures, that is,
      bulk layered heterojunctions (BLHJs) of Cu-Mo-S that contain MoS2 flakes inside,
      which are uniformly dispersed in the Cu2S matrix. The resulting structures were
      expected to induce asymmetric charge transfer via layered frameworks and tested
      as electrocatalysts for HERs. Upon suitable thermal treatments, the BLHJ surfaces
      exhibited the efficient HER performance of approximately 10 mA/cm2 at a potential
      of -0.1 V versus a reversible hydrogen electrode. The Tafel slope was
      approximately 30 to 40 mV per decade. The present strategy was further
      generalized by demonstrating the formation of BLHJs on other transition metals,
      such as Ni. The resulting BLHJs of Ni-Mo-S also showed the remarkable HER
      performance and the stable operation over 10 days without using Pt counter
      electrodes by eliminating any possible issues on the Pt contamination.

PMID- 28435864
TI  - Microbial arms race: Ballistic "nematocysts" in dinoflagellates represent a new
      extreme in organelle complexity.
AB  - We examine the origin of harpoon-like secretory organelles (nematocysts) in
      dinoflagellate protists. These ballistic organelles have been hypothesized to be
      homologous to similarly complex structures in animals (cnidarians); but we show,
      using structural, functional, and phylogenomic data, that nematocysts evolved
      independently in both lineages. We also recorded the first high-resolution videos
      of nematocyst discharge in dinoflagellates. Unexpectedly, our data suggest that
      different types of dinoflagellate nematocysts use two fundamentally different
      types of ballistic mechanisms: one type relies on a single pressurized capsule
      for propulsion, whereas the other type launches 11 to 15 projectiles from an
      arrangement similar to a Gatling gun. Despite their radical structural
      differences, these nematocysts share a single origin within dinoflagellates and
      both potentially use a contraction-based mechanism to generate ballistic force.
      The diversity of traits in dinoflagellate nematocysts demonstrates a stepwise
      route by which simple secretory structures diversified to yield elaborate
      subcellular weaponry.

PMID- 28435865
TI  - Time-reversal symmetry-breaking superconductivity in epitaxial bismuth/nickel
      bilayers.
AB  - Superconductivity that spontaneously breaks time-reversal symmetry (TRS) has been
      found, so far, only in a handful of three-dimensional (3D) crystals with bulk
      inversion symmetry. We report an observation of spontaneous TRS breaking in a 2D
      superconducting system without inversion symmetry: the epitaxial bilayer films of
      bismuth and nickel. The evidence comes from the onset of the polar Kerr effect at
      the superconducting transition in the absence of an external magnetic field,
      detected by the ultrasensitive loop-less fiber-optic Sagnac interferometer.
      Because of strong spin-orbit interaction and lack of inversion symmetry in a
      Bi/Ni bilayer, superconducting pairing cannot be classified as singlet or
      triplet. We propose a theoretical model where magnetic fluctuations in Ni induce
      the superconducting pairing of the [Formula: see text] orbital symmetry between
      the electrons in Bi. In this model, the order parameter spontaneously breaks the
      TRS and has a nonzero phase winding number around the Fermi surface, thus making
      it a rare example of a 2D topological superconductor.

PMID- 28435866
TI  - Layered microporous polymers by solvent knitting method.
AB  - Two-dimensional (2D) nanomaterials, especially 2D organic nanomaterials with
      unprecedentedly diverse and controlled structure, have attracted decent
      scientific interest. Among the preparation strategies, the top-down approach is
      one of the considered low-cost and scalable strategies to obtain 2D organic
      nanomaterials. However, some factors of their layered counterparts limited the
      development and potential applications of 2D organic nanomaterials, such as type,
      stability, and strict synthetic conditions of layered counterparts. We report a
      class of layered solvent knitting hyper-cross-linked microporous polymers (SHCPs)
      prepared by improving Friedel-Crafts reaction and using dichloroalkane as an
      economical solvent, stable electrophilic reagent, and external cross-linker at
      low temperature, which could be used as layered counterparts to obtain previously
      unknown 2D SHCP nanosheets by method of ultrasonic-assisted solvent exfoliation.
      This efficient and low-cost strategy can produce previously unreported
      microporous organic polymers with layered structure and high surface area and gas
      storage capacity. The pore structure and surface area of these polymers can be
      controlled by tuning the chain length of the solvent, the molar ratio of AlCl3,
      and the size of monomers. Furthermore, we successfully obtain an unprecedentedly
      high-surface area HCP material (3002 m2 g-1), which shows decent gas storage
      capacity (4.82 mmol g-1 at 273 K and 1.00 bar for CO2; 12.40 mmol g-1 at 77.3 K
      and 1.13 bar for H2). This finding provides an opportunity for breaking the
      constraint of former knitting methods and opening up avenues for the design and
      synthesis of previously unknown layered HCP materials.

PMID- 28435867
TI  - Heterojunction oxide thin-film transistors with unprecedented electron mobility
      grown from solution.
AB  - Thin-film transistors made of solution-processed metal oxide semiconductors hold
      great promise for application in the emerging sector of large-area electronics.
      However, further advancement of the technology is hindered by limitations
      associated with the extrinsic electron transport properties of the often defect
      prone oxides. We overcome this limitation by replacing the single-layer
      semiconductor channel with a low-dimensional, solution-grown In2O3/ZnO
      heterojunction. We find that In2O3/ZnO transistors exhibit band-like electron
      transport, with mobility values significantly higher than single-layer In2O3 and
      ZnO devices by a factor of 2 to 100. This marked improvement is shown to
      originate from the presence of free electrons confined on the plane of the
      atomically sharp heterointerface induced by the large conduction band offset
      between In2O3 and ZnO. Our finding underscores engineering of solution-grown
      metal oxide heterointerfaces as an alternative strategy to thin-film transistor
      development and has the potential for widespread technological applications.

PMID- 28435868
TI  - Label-free optical detection of single enzyme-reactant reactions and associated
      conformational changes.
AB  - Monitoring the kinetics and conformational dynamics of single enzymes is crucial
      to better understand their biological functions because these motions and
      structural dynamics are usually unsynchronized among the molecules. However,
      detecting the enzyme-reactant interactions and associated conformational changes
      of the enzyme on a single-molecule basis remains as a challenge to established
      optical techniques because of the commonly required labeling of the reactants or
      the enzyme itself. The labeling process is usually nontrivial, and the labels
      themselves might skew the physical properties of the enzyme. We demonstrate an
      optical, label-free method capable of observing enzymatic interactions and
      associated conformational changes on a single-molecule level. We monitor
      polymerase/DNA interactions via the strong near-field enhancement provided by
      plasmonic nanorods resonantly coupled to whispering gallery modes in
      microcavities. Specifically, we use two different recognition schemes: one in
      which the kinetics of polymerase/DNA interactions are probed in the vicinity of
      DNA-functionalized nanorods, and the other in which these interactions are probed
      via the magnitude of conformational changes in the polymerase molecules
      immobilized on nanorods. In both approaches, we find that low and high polymerase
      activities can be clearly discerned through their characteristic signal amplitude
      and signal length distributions. Furthermore, the thermodynamic study of the
      monitored interactions suggests the occurrence of DNA polymerization. This work
      constitutes a proof-of-concept study of enzymatic activities using plasmonically
      enhanced microcavities and establishes an alternative and label-free method
      capable of investigating structural changes in single molecules.

PMID- 28435869
TI  - A dynamic hydrophobic core orchestrates allostery in protein kinases.
AB  - Eukaryotic protein kinases (EPKs) constitute a class of allosteric switches that
      mediate a myriad of signaling events. It has been postulated that EPKs' active
      and inactive states depend on the structural architecture of their hydrophobic
      cores, organized around two highly conserved spines: C-spine and R-spine. How the
      spines orchestrate the transition of the enzyme between catalytically uncommitted
      and committed states remains elusive. Using relaxation dispersion nuclear
      magnetic resonance spectroscopy, we found that the hydrophobic core of the
      catalytic subunit of protein kinase A, a prototypical and ubiquitous EPK, moves
      synchronously to poise the C subunit for catalysis in response to binding
      adenosine 5'-triphosphate. In addition to completing the C-spine, the adenine
      ring fuses the beta structures of the N-lobe and the C-lobe. Additional residues
      that bridge the two spines (I150 and V104) are revealed as part of the correlated
      hydrophobic network; their importance was validated by mutagenesis, which led to
      inactivation. Because the hydrophobic architecture of the catalytic core is
      conserved throughout the EPK superfamily, the present study suggests a universal
      mechanism for dynamically driven allosteric activation of kinases mediated by
      coordinated signal transmission through ordered motifs in their hydrophobic
      cores.

PMID- 28435871
TI  - Recovery of an oxidized majorite inclusion from Earth's deep asthenosphere.
AB  - Minerals recovered from the deep mantle provide a rare glimpse into deep Earth
      processes. We report the first discovery of ferric iron-rich majoritic garnet
      found as inclusions in a host garnet within an eclogite xenolith originating in
      the deep mantle. The composition of the host garnet indicates an ultrahigh
      pressure metamorphic origin, probably at a depth of ~200 km. More importantly,
      the ferric iron-rich majoritic garnet inclusions show a much deeper origin, at
      least at a depth of 380 km. The majoritic nature of the inclusions is confirmed
      by mineral chemistry, x-ray diffraction, and Raman spectroscopy, and their depth
      of origin is constrained by a new experimental calibration. The unique
      relationship between the majoritic inclusions and their host garnet has important
      implications for mantle dynamics within the deep asthenosphere. The high ferric
      iron content of the inclusions provides insights into the oxidation state of the
      deep upper mantle.

PMID- 28435870
TI  - Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug
      delivery to airways following inhalation.
AB  - Mucoadhesive particles (MAP) have been widely explored for pulmonary drug
      delivery because of their perceived benefits in improving particle residence in
      the lungs. However, retention of particles adhesively trapped in airway mucus may
      be limited by physiologic mucus clearance mechanisms. In contrast, particles that
      avoid mucoadhesion and have diameters smaller than mucus mesh spacings rapidly
      penetrate mucus layers [mucus-penetrating particles (MPP)], which we hypothesized
      would provide prolonged lung retention compared to MAP. We compared in vivo
      behaviors of variously sized, polystyrene-based MAP and MPP in the lungs
      following inhalation. MAP, regardless of particle size, were aggregated and
      poorly distributed throughout the airways, leading to rapid clearance from the
      lungs. Conversely, MPP as large as 300 nm exhibited uniform distribution and
      markedly enhanced retention compared to size-matched MAP. On the basis of these
      findings, we formulated biodegradable MPP (b-MPP) with an average diameter of
      <300 nm and examined their behavior following inhalation relative to similarly
      sized biodegradable MAP (b-MAP). Although b-MPP diffused rapidly through human
      airway mucus ex vivo, b-MAP did not. Rapid b-MPP movements in mucus ex vivo
      correlated to a more uniform distribution within the airways and enhanced lung
      retention time as compared to b-MAP. Furthermore, inhalation of b-MPP loaded with
      dexamethasone sodium phosphate (DP) significantly reduced inflammation in a mouse
      model of acute lung inflammation compared to both carrier-free DP and DP-loaded
      MAP. These studies provide a careful head-to-head comparison of MAP versus MPP
      following inhalation and challenge a long-standing dogma that favored the use of
      MAP for pulmonary drug delivery.

PMID- 28435872
TI  - Unraveling self-assembly pathways of the 468-kDa proteolytic machine TET2.
AB  - The spontaneous formation of biological higher-order structures from smaller
      building blocks, called self-assembly, is a fundamental attribute of life.
      Although the protein self-assembly is a time-dependent process that occurs at the
      molecular level, its current understanding originates either from static
      structures of trapped intermediates or from modeling. Nuclear magnetic resonance
      (NMR) spectroscopy has the unique ability to monitor structural changes in real
      time; however, its size limitation and time-resolution constraints remain a
      challenge when studying the self-assembly of large biological particles. We
      report the application of methyl-specific isotopic labeling combined with
      relaxation-optimized NMR spectroscopy to overcome both size- and time-scale
      limitations. We report for the first time the self-assembly process of a half
      megadalton protein complex that was monitored at the structural level, including
      the characterization of intermediate states, using a mutagenesis-free strategy.
      NMR was used to obtain individual kinetics data on the different transient
      intermediates and the formation of final native particle. In addition,
      complementary time-resolved electron microscopy and native mass spectrometry were
      used to characterize the low-resolution structures of oligomerization
      intermediates.

PMID- 28435873
TI  - Role of damping in spin Seebeck effect in yttrium iron garnet thin films.
AB  - The role of damping in the spin Seebeck effect (SSE) was studied experimentally
      for the first time. The experiments used Y3Fe5O12 (YIG)/Pt bilayered structures
      where the YIG films exhibit very similar structural and static magnetic
      properties but very different damping. The data show that a decrease in the
      damping gives rise to an increase in the SSE coefficient, which is qualitatively
      consistent with some of the theoretical models. This response also shows quasi
      linear behavior, which was not predicted explicitly by previous studies. The data
      also indicate that the SSE coefficient shows no notable correlations with the
      enhanced damping due to spin pumping, which can be understood in the frame of two
      existing models.

PMID- 28435874
TI  - Toward garnet electrolyte-based Li metal batteries: An ultrathin, highly
      effective, artificial solid-state electrolyte/metallic Li interface.
AB  - Solid-state batteries are a promising option toward high energy and power
      densities due to the use of lithium (Li) metal as an anode. Among all solid
      electrolyte materials ranging from sulfides to oxides and oxynitrides, cubic
      garnet-type Li7La3Zr2O12 (LLZO) ceramic electrolytes are superior candidates
      because of their high ionic conductivity (10-3 to 10-4 S/cm) and good stability
      against Li metal. However, garnet solid electrolytes generally have poor contact
      with Li metal, which causes high resistance and uneven current distribution at
      the interface. To address this challenge, we demonstrate a strategy to engineer
      the garnet solid electrolyte and the Li metal interface by forming an
      intermediary Li-metal alloy, which changes the wettability of the garnet surface
      (lithiophobic to lithiophilic) and reduces the interface resistance by more than
      an order of magnitude: 950 ohm.cm2 for the pristine garnet/Li and 75 ohm.cm2 for
      the surface-engineered garnet/Li. Li7La2.75Ca0.25Zr1.75Nb0.25O12 (LLCZN) was
      selected as the solid-state electrolyte (SSE) in this work because of its low
      sintering temperature, stabilized cubic garnet phase, and high ionic
      conductivity. This low area-specific resistance enables a solid-state garnet
      SSE/Li metal configuration and promotes the development of a hybrid electrolyte
      system. The hybrid system uses the improved solid-state garnet SSE Li metal anode
      and a thin liquid electrolyte cathode interfacial layer. This work provides new
      ways to address the garnet SSE wetting issue against Li and get more stable cell
      performances based on the hybrid electrolyte system for Li-ion, Li-sulfur, and Li
      oxygen batteries toward the next generation of Li metal batteries.

PMID- 28435875
TI  - Mandrills use olfaction to socially avoid parasitized conspecifics.
AB  - The evolutionary transition from a solitary to a social lifestyle entails an
      elevated parasite cost because the social proximity associated with group living
      favors parasite transmission. Despite this cost, sociality is widespread in a
      large range of taxonomic groups. In this context, hosts would be expected to have
      evolved behavioral mechanisms to reduce the risk of parasite infection. Few
      empirical studies have focused on the influence of pathogen-mediated selection on
      the evolution of antiparasitic behavior in wild vertebrates. We report an
      adaptive functional relationship between parasitism and social behavior in
      mandrills, associated with evidence that they are able to gauge parasite status
      of their group members. Using long-term observations, controlled experiments, and
      chemical analyses, we show that (i) wild mandrills avoid grooming conspecifics
      infected with orofecally transmitted parasites; (ii) mandrills receive
      significantly more grooming after treatment that targets these parasites; (iii)
      parasitism influences the host's fecal odors; and (iv) mandrills selectively
      avoid fecal material from parasitized conspecifics. These behavioral adaptations
      reveal that selecting safe social partners may help primates to cope with
      parasite-mediated costs of sociality and that "behavioral immunity" plays a
      crucial role in the coevolutionary dynamics between hosts and their parasites.

PMID- 28435876
TI  - The economic value of grassland species for carbon storage.
AB  - Carbon storage by ecosystems is valuable for climate protection. Biodiversity
      conservation may help increase carbon storage, but the value of this influence
      has been difficult to assess. We use plant, soil, and ecosystem carbon storage
      data from two grassland biodiversity experiments to show that greater species
      richness increases economic value: Increasing species richness from 1 to 10 had
      twice the economic value of increasing species richness from 1 to 2. The marginal
      value of each additional species declined as species accumulated, reflecting the
      nonlinear relationship between species richness and plant biomass production. Our
      demonstration of the economic value of biodiversity for enhancing carbon storage
      provides a foundation for assessing the value of biodiversity for decisions about
      land management. Combining carbon storage with other ecosystem services affected
      by biodiversity may well enhance the economic arguments for conservation even
      further.

PMID- 28435877
TI  - Design and function of biomimetic multilayer water purification membranes.
AB  - Multilayer architectures in water purification membranes enable increased water
      throughput, high filter efficiency, and high molecular loading capacity. However,
      the preparation of membranes with well-organized multilayer structures, starting
      from the nanoscale to maximize filtration efficiency, remains a challenge. We
      report a complete strategy to fully realize a novel biomaterial-based multilayer
      nanoporous membrane via the integration of computational simulation and
      experimental fabrication. Our comparative computational simulations, based on
      coarse-grained models of protein nanofibrils and mineral plates, reveal that the
      multilayer structure can only form with weak interactions between nanofibrils and
      mineral plates. We demonstrate experimentally that silk nanofibril (SNF) and
      hydroxyapatite (HAP) can be used to fabricate highly ordered multilayer membranes
      with nanoporous features by combining protein self-assembly and in situ
      biomineralization. The production is optimized to be a simple and highly
      repeatable process that does not require sophisticated equipment and is suitable
      for scaled production of low-cost water purification membranes. These membranes
      not only show ultrafast water penetration but also exhibit broad utility and high
      efficiency of removal and even reuse (in some cases) of contaminants, including
      heavy metal ions, dyes, proteins, and other nanoparticles in water. Our
      biomimetic design and synthesis of these functional SNF/HAP materials have
      established a paradigm that could lead to the large-scale, low-cost production of
      multilayer materials with broad spectrum and efficiency for water purification,
      with applications in wastewater treatment, biomedicine, food industry, and the
      life sciences.

PMID- 28435878
TI  - Evolutionary dynamics of CRISPR gene drives.
AB  - The alteration of wild populations has been discussed as a solution to a number
      of humanity's most pressing ecological and public health concerns. Enabled by the
      recent revolution in genome editing, clustered regularly interspaced short
      palindromic repeats (CRISPR) gene drives-selfish genetic elements that can spread
      through populations even if they confer no advantage to their host organism-are
      rapidly emerging as the most promising approach. However, before real-world
      applications are considered, it is imperative to develop a clear understanding of
      the outcomes of drive release in nature. Toward this aim, we mathematically study
      the evolutionary dynamics of CRISPR gene drives. We demonstrate that the
      emergence of drive-resistant alleles presents a major challenge to previously
      reported constructs, and we show that an alternative design that selects against
      resistant alleles could greatly improve evolutionary stability. We discuss all
      results in the context of CRISPR technology and provide insights that inform the
      engineering of practical gene drive systems.

PMID- 28435880
TI  - Robust quantum optimizer with full connectivity.
AB  - Quantum phenomena have the potential to speed up the solution of hard
      optimization problems. For example, quantum annealing, based on the quantum
      tunneling effect, has recently been shown to scale exponentially better with
      system size than classical simulated annealing. However, current realizations of
      quantum annealers with superconducting qubits face two major challenges. First,
      the connectivity between the qubits is limited, excluding many optimization
      problems from a direct implementation. Second, decoherence degrades the success
      probability of the optimization. We address both of these shortcomings and
      propose an architecture in which the qubits are robustly encoded in continuous
      variable degrees of freedom. By leveraging the phenomenon of flux quantization,
      all-to-all connectivity with sufficient tunability to implement many relevant
      optimization problems is obtained without overhead. Furthermore, we demonstrate
      the robustness of this architecture by simulating the optimal solution of a small
      instance of the nondeterministic polynomial-time hard (NP-hard) and fully
      connected number partitioning problem in the presence of dissipation.

PMID- 28435879
TI  - Fast-moving soft electronic fish.
AB  - Soft robots driven by stimuli-responsive materials have unique advantages over
      conventional rigid robots, especially in their high adaptability for field
      exploration and seamless interaction with humans. The grand challenge lies in
      achieving self-powered soft robots with high mobility, environmental tolerance,
      and long endurance. We are able to advance a soft electronic fish with a fully
      integrated onboard system for power and remote control. Without any motor, the
      fish is driven solely by a soft electroactive structure made of dielectric
      elastomer and ionically conductive hydrogel. The electronic fish can swim at a
      speed of 6.4 cm/s (0.69 body length per second), which is much faster than
      previously reported untethered soft robotic fish driven by soft responsive
      materials. The fish shows consistent performance in a wide temperature range and
      permits stealth sailing due to its nearly transparent nature. Furthermore, the
      fish is robust, as it uses the surrounding water as the electric ground and can
      operate for 3 hours with one single charge. The design principle can be
      potentially extended to a variety of flexible devices and soft robots.

PMID- 28435881
TI  - The memory remains: Understanding collective memory in the digital age.
AB  - Recently developed information communication technologies, particularly the
      Internet, have affected how we, both as individuals and as a society, create,
      store, and recall information. The Internet also provides us with a great
      opportunity to study memory using transactional large-scale data in a
      quantitative framework similar to the practice in natural sciences. We make use
      of online data by analyzing viewership statistics of Wikipedia articles on
      aircraft crashes. We study the relation between recent events and past events and
      particularly focus on understanding memory-triggering patterns. We devise a
      quantitative model that explains the flow of viewership from a current event to
      past events based on similarity in time, geography, topic, and the hyperlink
      structure of Wikipedia articles. We show that, on average, the secondary flow of
      attention to past events generated by these remembering processes is larger than
      the primary attention flow to the current event. We report these previously
      unknown cascading effects.

PMID- 28435882
TI  - Geochemical evidence for melange melting in global arcs.
AB  - In subduction zones, sediments and hydrothermally altered oceanic crust, which
      together form part of the subducting slab, contribute to the chemical composition
      of lavas erupted at the surface to form volcanic arcs. Transport of this material
      from the slab to the overlying mantle wedge is thought to involve discreet melts
      and fluids that are released from various portions of the slab. We use a meta
      analysis of geochemical data from eight globally representative arcs to show that
      melts and fluids from individual slab components cannot be responsible for the
      formation of arc lavas. Instead, the data are compatible with models that first
      invoke physical mixing of slab components and the mantle wedge, widely referred
      to as high-pressure melange, before arc magmas are generated.

PMID- 28435883
TI  - Normal sleep requires the astrocyte brain-type fatty acid binding protein FABP7.
AB  - Sleep is found widely in the animal kingdom. Despite this, few conserved
      molecular pathways that govern sleep across phyla have been described. The
      mammalian brain-type fatty acid binding protein (Fabp7) is expressed in
      astrocytes, and its mRNA oscillates in tandem with the sleep-wake cycle. However,
      the role of FABP7 in regulating sleep remains poorly understood. We found that
      the missense mutation FABP7.T61M is associated with fragmented sleep in humans.
      This phenotype was recapitulated in mice and fruitflies bearing similar
      mutations: Fabp7-deficient mice and transgenic flies that express the FABP7.T61M
      missense mutation in astrocytes also show fragmented sleep. These results provide
      novel evidence for a distinct molecular pathway linking lipid-signaling cascades
      within astrocytes in sleep regulation among phylogenetically disparate species.

PMID- 28435884
TI  - Exercise Intervention Improves the Metabolic Profile and Body Composition of
      Southwestern American Indian Adolescents.
AB  - INTRODUCTION/PURPOSE: The Southwestern American Indian population carries a high
      prevalence of metabolic syndrome and obesity, placing this group at higher risk
      than the general population for developing early type 2 diabetes and
      cardiovascular disease, likely impacting overall lifespan. This study aims to
      evaluate the impact of early lifestyle interventions which promote healthy eating
      and regular exercise on risk factors contributing to the development of the
      metabolic syndrome among the adolescent Zuni Pueblo population. MATERIALS AND
      METHODS: We describe a prospective, single site, community-based cohort study
      performed among sixty-five adolescent Zuni Indians aged 13.9 +/- 1.7 years who
      were recruited between March 2011 and January 2014. The study intervention
      consisted of a targeted, tri-weekly exercise regimen with nutritional
      counselling, and the primary study outcomes included changes from baseline in
      metabolic profile (fasting lipids, A1c), vital signs (blood pressure, resting
      heart rate) and anthropometric characteristics of the study group. RESULTS: 41
      participants have anthropometric data measured at baseline and after completion,
      biochemical data are available from 30 participants, and body composition data
      from 26 patients. Using the paired Student's t-test with Bonferroni correction,
      significant improvements were shown in pediatric BMI percentile, fasting lipid
      profile, A1C, total body fat, and fat free mass after six months of exercise and
      nutritional intervention. CONCLUSIONS: A simple, standardized fitness program
      among Southwest American Indian adolescents was effective at reducing fasting
      lipids and adiposity, as well as improving glycemic indices over the course of
      six months.

PMID- 28435885
TI  - Phylogenomic Reconstruction of the Oomycete Phylogeny Derived from 37 Genomes.
AB  - The oomycetes are a class of microscopic, filamentous eukaryotes within the
      Stramenopiles-Alveolata-Rhizaria (SAR) supergroup which includes ecologically
      significant animal and plant pathogens, most infamously the causative agent of
      potato blight Phytophthora infestans. Single-gene and concatenated phylogenetic
      studies both of individual oomycete genera and of members of the larger class
      have resulted in conflicting conclusions concerning species phylogenies within
      the oomycetes, particularly for the large Phytophthora genus. Genome-scale
      phylogenetic studies have successfully resolved many eukaryotic relationships by
      using supertree methods, which combine large numbers of potentially disparate
      trees to determine evolutionary relationships that cannot be inferred from
      individual phylogenies alone. With a sufficient amount of genomic data now
      available, we have undertaken the first whole-genome phylogenetic analysis of the
      oomycetes using data from 37 oomycete species and 6 SAR species. In our analysis,
      we used established supertree methods to generate phylogenies from 8,355
      homologous oomycete and SAR gene families and have complemented those analyses
      with both phylogenomic network and concatenated supermatrix analyses. Our results
      show that a genome-scale approach to oomycete phylogeny resolves oomycete classes
      and individual clades within the problematic Phytophthora genus. Support for the
      resolution of the inferred relationships between individual Phytophthora clades
      varies depending on the methodology used. Our analysis represents an important
      first step in large-scale phylogenomic analysis of the oomycetes. IMPORTANCE The
      oomycetes are a class of eukaryotes and include ecologically significant animal
      and plant pathogens. Single-gene and multigene phylogenetic studies of individual
      oomycete genera and of members of the larger classes have resulted in conflicting
      conclusions concerning interspecies relationships among these species,
      particularly for the Phytophthora genus. The onset of next-generation sequencing
      techniques now means that a wealth of oomycete genomic data is available. For the
      first time, we have used genome-scale phylogenetic methods to resolve oomycete
      phylogenetic relationships. We used supertree methods to generate single-gene and
      multigene species phylogenies. Overall, our supertree analyses utilized
      phylogenetic data from 8,355 oomycete gene families. We have also complemented
      our analyses with superalignment phylogenies derived from 131 single-copy
      ubiquitous gene families. Our results show that a genome-scale approach to
      oomycete phylogeny resolves oomycete classes and clades. Our analysis represents
      an important first step in large-scale phylogenomic analysis of the oomycetes.

PMID- 28435886
TI  - Discovery of a Novel Antifungal Agent in the Pathogen Box.
AB  - Human fungal pathogens cause over 2 million infections per year and are major
      drivers of morbidity and mortality. Cryptococcus neoformans and Candida albicans
      are two of the most common fungal pathogens of humans, together accounting for a
      staggering 1.4 million infections annually, with very high mortality rates.
      Patients with dysfunctional immune systems, such as individuals with HIV/AIDS,
      are particularly susceptible to fungal infections. Unfortunately, relatively few
      antifungal drugs are currently available and fungi frequently develop resistance,
      further complicating treatment approaches. In this study, we screened the
      Pathogen Box chemical library (Medicines for Malaria Venture, Switzerland) in an
      effort to identify novel antifungal compounds. This approach led to the discovery
      of a novel, highly potent antifungal agent with activity against both C.
      neoformans and C. albicans. Our initial study of the mechanism of action
      suggested that this novel compound prevents fungal proliferation by targeting the
      ability of C. neoformans to withstand stress at the plasma membrane and cell
      wall. Because this compound had previously been shown to have low toxicity for
      mammalian cells, we propose that it represents an attractive lead compound for
      further antifungal drug development. IMPORTANCECryptococcus neoformans and
      Candida albicans are two major human fungal pathogens and together account for
      over 1.4 million infections annually, with very high mortality rates. These fungi
      often infect immunocompromised individuals, such as HIV/AIDS patients. In an
      effort to identify novel drugs with antifungal activity, we have screened the
      Pathogen Box for compounds with anticryptococcal and anticandidal activities.
      This approach led to the discovery of a promising lead compound (MMV688271) with
      strong antifungal potency under nutrient-limited conditions.

PMID- 28435887
TI  - Correction for Mahic et al., "Maternal Immunoreactivity to Herpes Simplex Virus 2
      and Risk of Autism Spectrum Disorder in Male Offspring".
AB  - [This corrects the article DOI: 10.1128/mSphere.00016-17.].

PMID- 28435888
TI  - Continental Drift and Speciation of the Cryptococcus neoformans and Cryptococcus
      gattii Species Complexes.
AB  - Genomic analysis has placed the origins of two human-pathogenic fungi, the
      Cryptococcus gattii species complex and the Cryptococcus neoformans species
      complex, in South America and Africa, respectively. Molecular clock calculations
      suggest that the two species separated ~80 to 100 million years ago. This time
      closely approximates the breakup of the supercontinent Pangea, which gave rise to
      South America and Africa. On the basis of the geographic distribution of these
      two species complexes and the coincidence of the evolutionary divergence and
      Pangea breakup times, we propose that a spatial separation caused by continental
      drift resulted in the emergence of the C. gattii and C. neoformans species
      complexes from a Pangean ancestor. We note that, despite the spatial and temporal
      separation that occurred approximately 100 million years ago, these two species
      complexes are morphologically similar, share virulence factors, and cause very
      similar diseases. Continuation of these phenotypic characteristics despite
      ancient separation suggests the maintenance of similar selection pressures
      throughout geologic ages.

PMID- 28435889
TI  - Multidrug Resistance Salmonella Genomic Island 1 in a Morganella morganii subsp.
      morganii Human Clinical Isolate from France.
AB  - Salmonella genomic island 1 (SGI1) is a multidrug resistance integrative
      mobilizable element that harbors a great diversity of antimicrobial resistance
      gene clusters described in numerous Salmonella enterica serovars and also in
      Proteus mirabilis. A serious threat to public health was revealed in the recent
      description in P. mirabilis of a SGI1-derivative multidrug resistance island
      named PGI1 (Proteus genomic island 1) carrying extended-spectrum-beta-lactamase
      (ESBL) and metallo-beta-lactamase resistance genes, blaVEB-6 and blaNDM-1,
      respectively. Here, we report the first description of Salmonella genomic island
      1 (SGI1) in a multidrug-resistant clinical Morganella morganii subsp. morganii
      strain isolated from a patient in France in 2013. Complete-genome sequencing of
      the strain revealed SGI1 variant SGI1-L carrying resistance genes dfrA15, floR,
      tetA(G), blaPSE-1 (now referred to as blaCARB-2), and sul1, conferring resistance
      to trimethoprim, phenicols, tetracyclines, amoxicillin, and sulfonamides,
      respectively. The SGI1-L variant was integrated into the usual chromosome
      specific integration site at the 3' end of the trmE gene. Beyond Salmonella
      enterica and Proteus mirabilis, the SGI1 integrative mobilizable element may thus
      also disseminate its multidrug resistance phenotype in another genus belonging to
      the Proteae tribe of the family Enterobacteriaceae. IMPORTANCE Since its initial
      identification in epidemic multidrug-resistant Salmonella enterica serovar
      Typhimurium DT104 strains, several SGI1 variants, SGI1 lineages, and SGI1-related
      elements (SGI2, PGI1, and AGI1) have been described in many bacterial genera
      (Salmonella, Proteus, Morganella, Vibrio, Shewanella, etc.). They constitute a
      family of multidrug resistance site-specific integrative elements acquired by
      horizontal gene transfer, SGI1 being the best-characterized element. The
      horizontal transfer of SGI1/PGI1 elements into other genera is of public health
      concern, notably with regard to the spread of critically important resistance
      genes such as ESBL and carbapenemase genes. The identification of SGI1 in
      Morganella morganii raises the issue of (i) the potential for SGI1 to emerge in
      other human pathogens and (ii) its bacterial host range. Further surveillance and
      research are needed to understand the epidemiology, the spread, and the
      importance of the members of this SGI1 family of integrative elements in
      contributing to antibiotic resistance development.

PMID- 28435890
TI  - Gene Expression Profile of Human Cytokines in Response to Burkholderia
      pseudomallei Infection.
AB  - Melioidosis is an underreported infectious disease, caused by the Gram-negative
      bacterium Burkholderia pseudomallei. Understanding the disease susceptibility and
      pathogenesis is crucial for developing newer diagnostic and therapeutic
      strategies for this life-threatening infection. In this study, we aimed to
      analyze the gene expression levels of important cytokines in melioidosis patients
      and establish useful correlates with disease biomarkers compared to cases of
      sepsis infection caused by other pathogens and healthy individuals. A Qiagen
      common human cytokines array profiling the gene expression of 84 important
      cytokines by real-time quantitative PCR (RT-qPCR) was used. We analyzed 26
      melioidosis cases, 5 healthy controls, and 10 cases of sepsis infection caused by
      other pathogens. Our results showed consistently upregulated expression of
      interleukins (IL) interleukin-4 (IL-4), interleukin-17 alpha (IL-17A), IL-23A,
      and IL-24, interferons (IFN) interferon alpha 1 (IFNA1) and interferon beta 1
      (IFNB1), tumor necrosis factor (TNF) superfamily 4 (TNFSF4), transforming growth
      factor (TGF) superfamily, bone morphogenetic proteins 3 and 6 (BMP3 and BMP6),
      transforming growth factor beta 1 (TGFB1), and other growth factors, including
      macrophage colony-stimulating factor (M-CSF), C-fos-induced growth factor (FIGF),
      and platelet-derived growth factor alpha (PDGFA) polypeptide, in melioidosis
      patients compared to their expression in other sepsis cases, irrespective of
      comorbidities, duration of fever/clinical symptoms, and antibiotic treatment. Our
      findings indicate a dominant Th2- and Th17-type-cytokine response, suggesting
      that their dysregulation at initial stages of infection may play an important
      role in disease pathogenesis. IL-1A, interleukin-1 beta (IL-1B), and IL-8 were
      significantly downregulated in septicemic melioidosis patients compared to their
      expression in other sepsis cases. These differentially expressed genes may serve
      as biomarkers for melioidosis diagnosis and targets for therapeutic intervention
      and may help us understand immune response mechanisms. IMPORTANCE Melioidosis is
      a life-threatening infectious disease caused by a soil-associated Gram-negative
      bacterium, B. pseudomallei. Melioidosis is endemic in Southeast Asia and northern
      Australia; however, the global distribution of B. pseudomallei and the disease
      burden of melioidosisis are still poorly understood. Melioidosis is difficult to
      treat, as B. pseudomallei is intrinsically resistant to many antibiotics and
      requires a long course of antibiotic treatment. The mortality rates remain high
      in areas of endemicity, with reoccurrence being common. Therefore, it is
      imperative to diagnose the disease at an early stage and provide vital clinical
      care to reduce the mortality rate. With limitations in treatment and lack of a
      vaccine, it is crucial to study the immune response mechanisms to this infection
      to get a better understanding of disease susceptibility and pathogenesis.
      Therefore, this study aimed to analyze the gene expression levels of important
      cytokines to establish useful correlations for diagnostic and therapeutic
      purposes.

PMID- 28435891
TI  - Detection of Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi,
      Borrelia miyamotoi, and Powassan Virus in Ticks by a Multiplex Real-Time Reverse
      Transcription-PCR Assay.
AB  - Ixodes scapularis ticks are implicated in transmission of Anaplasma
      phagocytophilum, Borrelia burgdorferi, Borrelia miyamotoi, Babesia microti, and
      Powassan virus. We describe the establishment and implementation of the first
      multiplex real-time PCR assay with the capability to simultaneously detect and
      differentiate all five pathogens in a single reaction. The application of this
      assay for analysis of ticks at sites in New York and Connecticut revealed a high
      prevalence of B. microti in ticks from Suffolk County, NY. These findings are
      consistent with reports of a higher incidence of babesiosis from clinicians
      managing the care of patients with tick-borne diseases in this region. IMPORTANCE
      The understanding of pathogen prevalence is an important factor in the
      determination of human risks for tick-borne diseases and can help guide diagnosis
      and treatment. The implementation of our assay addresses a critical need in
      surveillance of tick-borne diseases, through generation of a comprehensive
      assessment of pathogen prevalence in I. scapularis. Our finding of a high
      frequency of ticks infected with Babesia microti in Suffolk County, NY,
      implicates this agent as a probable frequent cause of non-Lyme tick-borne disease
      in this area.

PMID- 28435892
TI  - Dramatic Improvement of CRISPR/Cas9 Editing in Candida albicans by Increased
      Single Guide RNA Expression.
AB  - The clustered regularly interspaced short palindromic repeat system with CRISPR
      associated protein 9 nuclease (CRISPR/Cas9) has emerged as a versatile tool for
      genome editing in Candida albicans. Mounting evidence from other model systems
      suggests that the intracellular levels of single guide RNA (sgRNA) limit the
      efficiency of Cas9-dependent DNA cleavage. Here, we tested this idea and describe
      a new means of sgRNA delivery that improves previously described methods by ~10
      fold. The efficiency of Cas9/sgRNA-dependent cleavage and repair of a single-copy
      yeast enhanced monomeric red fluorescent protein (RFP) gene was measured as a
      function of various parameters that are hypothesized to affect sgRNA
      accumulation, including transcriptional and posttranscriptional processing. We
      analyzed different promoters (SNR52, ADH1, and tRNA), as well as different
      posttranscriptional RNA processing schemes that serve to generate or stabilize
      mature sgRNA with precise 5' and 3' ends. We compared the effects of flanking
      sgRNA with self-cleaving ribozymes or by tRNA, which is processed by endogenous
      RNases. These studies demonstrated that sgRNA flanked by a 5' tRNA and
      transcribed by a strong RNA polymerase II ADH1 promoter increased Cas9-dependent
      RFP mutations by 10-fold. Examination of double-strand-break (DSB) repair in
      strains hemizygous for RFP demonstrated that both homology-directed and
      nonhomologous end-joining pathways were used to repair breaks. Together, these
      results support the model that gRNA expression can be rate limiting for efficient
      CRISPR/Cas mutagenesis in C. albicans. IMPORTANCECandida albicans is an important
      human fungal pathogen. An understanding of fungal virulence factors has been slow
      because C. albicans is genetically intractable. The recent development of
      CRISPR/Cas in C. albicans (V. K. Vyas, M. I. Barrasa, G. R. Fink, Sci Adv
      1:e1500248, 2015, https://doi.org/10.1126/sciadv.1500248) has the potential to
      circumvent this problem. However, as has been found in other organisms,
      CRISPR/Cas mutagenesis efficiency can be frustratingly variable. Here, we
      systematically examined parameters hypothesized to alter sgRNA intracellular
      levels in order to optimize CRISPR/Cas in C. albicans. Our most important
      conclusion is that increased sgRNA expression and maturation dramatically improve
      efficiency of CRISPR/Cas mutagenesis in C. albicans by ~10-fold. Thus, we
      anticipate that the modifications described here will further advance the
      application of CRISPR/Cas for genome editing in C. albicans.

PMID- 28435893
TI  - Opacification Domain of Serum Opacity Factor Inhibits Beta-Hemolysis and
      Contributes to Virulence of Streptococcus pyogenes.
AB  - Serum opacity factor (SOF) is a cell surface virulence factor made by the human
      pathogen Streptococcus pyogenes. We found that S. pyogenes strains with naturally
      occurring truncation mutations in the sof gene have markedly enhanced beta
      hemolysis. Moreover, deletion of the sof gene in a SOF-positive parental strain
      resulted in significantly increased beta-hemolysis. Together, these observations
      suggest that SOF is an inhibitor of beta-hemolysis. SOF has two major functional
      domains, including an opacification domain and a fibronectin-binding domain.
      Using a SOF-positive serotype M89 S. pyogenes parental strain and a panel of
      isogenic mutant derivative strains, we evaluated the relative contribution of
      each SOF functional domain to beta-hemolysis inhibition and bacterial virulence.
      We found that the opacification domain, rather than the fibronectin-binding
      domain, is essential for SOF-mediated beta-hemolysis inhibition. The
      opacification domain, but not the fibronectin-binding domain of SOF, also
      contributed significantly to virulence in mouse models of bacteremia and
      necrotizing myositis. Inasmuch as the opacification domain of SOF is known to
      interact avidly with host high-density lipoprotein (HDL), we speculate that SOF
      HDL interaction is an important process underlying SOF-mediated beta-hemolysis
      inhibition and SOF-mediated virulence. IMPORTANCEStreptococcus pyogenes is a
      major human pathogen causing more than 700 million infections annually. As a
      successful pathogen, S. pyogenes produces many virulence factors that facilitate
      colonization, proliferation, dissemination, and tissue damage. Serum opacity
      factor (SOF), an extracellular protein, is one of the virulence factors made by
      S. pyogenes. The underlying mechanism of how SOF contributes to virulence is not
      fully understood. SOF has two major features: (i) it opacifies host serum by
      interacting with high-density lipoprotein, and (ii) it inhibits beta-hemolysis on
      blood agar. In this study, we demonstrate that the domain of SOF essential for
      opacifying serum is also essential for SOF-mediated beta-hemolysis inhibition and
      SOF-mediated virulence. Our results shed new light on the molecular mechanisms of
      SOF-host interaction.

PMID- 28435895
TI  - PubMed inclusion: Clinical and Experimental Emergency Medicine joins the club.

PMID- 28435894
TI  - Oral Bacterial Acid-Base Metabolism in Caries Screening: A Proof-Of-Concept
      Study.
AB  - The objective of this cross-sectional study was to clinically validate an array
      of biochemical tests for oral acid/alkali generation as caries screening
      instruments. 185 adult subjects (mean 33.6+/-10.6 years) were examined clinically
      for dental caries using the ICDAS criteria. Bitewing radiographs were used to
      confirm interproximal surfaces of posterior teeth. For the purposes of this
      study, subjects were classified as "caries-active" if they had at least one
      untreated caries lesion with ICDAS 4 or higher. Pooled supragingival plaque and
      unstimulated saliva samples were collected and assayed for pH changes from
      sucrose and urea metabolism using colorimetric tests. The validity of each test
      to discriminate between "caries-inactive" and "caries-active" subjects was
      assessed and compared to a commercial bacteriological caries-screening test using
      roc regression and logistic regression models. The AUCs of the plaque-urea (PU:
      0.59 (0.51, 0.67)), plaque-urea-glucose (PUG: 0.59 (0.51, 0.67)) and saliva-urea
      glucose (SUG: 0.59 (0.51, 0.67)) tests did not differ significantly from the
      bacteriological tests (CRT-mutans: 0.62 (0.54, 0.70); CRT-lactobacillus: 0.63
      (0.56, 0.71) (P>0.05), but the plaque-glucose (SG), saliva-glucose (SG), saliva
      urea (SU) and saliva-plaque-glucose (SPG) tests had significantly smaller AUCs
      (P<0.05). The AUCs for the PU, PUG, SUG, and the CRT-mutans tests were higher in
      subjects who had no existing dental restorations (PU: 0.90 (0.77, 1.04); PUG:
      0.90 (0.79, 1.01); SUG: 0.89 (0.69, 1.08); CRT-mutans: 0.90 (0.73, 1.08)). The
      incorporation of the biochemical tests into a multidimensional
      bacteriological/psychosocial caries screening model significantly increased its
      diagnostic values (Se+Sp: 160.6, AUC: 0.846). In conclusion, as a proof of
      concept, the results of this study indicate that measuring the ability of dental
      plaque and saliva to metabolize urea together with the ability to generate acid
      from sugars may have a promising role in caries screening either independently,
      or as part of a multidimensional biological test.

PMID- 28435896
TI  - Association between persistent tachycardia and tachypnea and in-hospital
      mortality among non-hypotensive emergency department patients admitted to the
      hospital.
AB  - OBJECTIVE: Vital sign trends are used in clinical practice to assess treatment
      response and aid in disposition, yet quantitative data to support this practice
      are lacking. This study aimed to determine the prognostic value of vital sign
      normalization. METHODS: Secondary analysis of a prospective cohort of adult
      emergency department (ED) patients admitted a single urban tertiary care
      hospital. A random sample of 182 days was chosen, and a manual review of all
      admissions was undertaken. Persistent tachycardia or tachypnea was defined as
      failure to decrease to a normal value in the ED. Elevated upon admission was
      defined as an abnormal value at the last set of vital signs documented. The
      primary outcome was in-hospital mortality. RESULTS: 4,878 patients were enrolled
      and 4.5 (+/-3.8) sets of vital signs were checked per patient. 1,770 patients
      were tachycardic and 1,499 were tachypneic. Among tachycardic patients, 941 (53%)
      were persistently tachycardic and 1,074 (61%) were tachycardic upon admission.
      Among tachypneic patients 639 (42%) were persistently tachypneic and 768 (51%)
      were tachypneic upon admission. Mortality was higher in patients persistently
      tachycardic (5.7% vs. 3.1%, P=0.008) or tachycardic upon admission (5.5% vs.
      3.0%, P=0.014). Similar results were found in tachypneic patients (8.3% vs. 4.5%,
      P=0.003; 7.8% vs. 4.4%, P=0.006). CONCLUSION: Persistent tachycardia and
      tachypnea are associated with an increased risk of mortality in ED patients
      admitted to the hospital. Further study is necessary to determine if improved
      recognition or earlier interventions can affect outcomes.

PMID- 28435897
TI  - Association between lactate clearance during post-resuscitation care and
      neurologic outcome in cardiac arrest survivors treated with targeted temperature
      management.
AB  - OBJECTIVE: We investigated the association between lactate clearance or serum
      lactate levels and neurologic outcomes or in-hospital mortality in cardiac arrest
      survivors who were treated with targeted temperature management (TTM). METHODS: A
      retrospective analysis of data from cardiac arrest survivors treated with TTM
      between 2012 and 2015 was conducted. Serum lactate levels were measured on
      admission and at 12, 24, and 48 hours following admission. Lactate clearance at
      12, 24, and 48 hours was also calculated. The primary outcome was neurologic
      outcome at discharge. The secondary outcome was in-hospital mortality. RESULTS:
      The study included 282 patients; 184 (65.2%) were discharged with a poor
      neurologic outcome, and 62 (22.0%) died. Higher serum lactate levels at 12 hours
      (odds ratio [OR], 1.157; 95% confidence interval [CI], 1.006 to 1.331), 24 hours
      (OR, 1.320; 95% CI, 1.084 to 1.607), and 48 hours (OR, 2.474; 95% CI, 1.459 to
      4.195) after admission were associated with a poor neurologic outcome.
      Furthermore, a higher serum lactate level at 48 hours (OR, 1.459; 95% CI, 1.181
      to 1.803) following admission was associated with in-hospital mortality. Lactate
      clearance was not associated with neurologic outcome or in-hospital mortality at
      any time point after adjusting for confounders. CONCLUSION: Increased serum
      lactate levels after admission are associated with a poor neurologic outcome at
      discharge and in-hospital mortality in cardiac arrest survivors treated with TTM.
      Conversely, lactate clearance is not a robust surrogate marker of neurologic
      outcome or in-hospital mortality.

PMID- 28435898
TI  - High-sensitivity C-reactive protein/albumin ratio as a predictor of in-hospital
      mortality in older adults admitted to the emergency department.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that an
      elevated high-sensitivity C-reactive protein (hs-CRP)/albumin ratio at admission
      increases the risk of mortality in older patients admitted to the hospital via
      the emergency department (ED). METHODS: We performed a retrospective analysis of
      patients admitted to the ED with any medical problem between May 2013 and October
      2013 who were older than 65 years. The hs-CRP and albumin levels were measured at
      the time of admission to the ED. The primary outcome was all-cause in-hospital
      mortality. Multivariate logistic analysis was performed. RESULTS: A total of 811
      patients were finally included in this study. The mean age was 76+/-7 years, and
      438 subjects (54%) were male. The in-hospital mortality rate was 9.0% (73
      patients). The hs-CRP/albumin ratio was higher in nonsurvivors than in survivors
      (34.2+/-37.6 vs. 16.2+/-25.5, P<0.001). Multivariate logistic analysis showed
      that the hs-CRP/albumin ratio was associated with all-cause in-hospital mortality
      after adjusting for other confounding factors (odds ratio, 1.011; 95% confidence
      interval [CI], 1.003 to 1.020). The prognostic value of the hs-CRP/albumin ratio
      for predicting mortality (area under the curve, 0.728; 95% CI, 0.696 to 0.758)
      was greater than that of hs-CRP alone (area under the curve, 0.706; 95% CI, 0.674
      to 0.738; P<0.001). CONCLUSION: The hs-CRP/albumin ratio at admission to the ED
      is associated with all-cause in-hospital mortality among patients older than 65
      years. The hs-CRP/albumin ratio may serve as a surrogate marker of disease
      severity.

PMID- 28435899
TI  - Hematologic parameters to predict negative cerebrospinal fluid examination
      results among neurologically intact patients who underwent lumbar puncture on
      suspicion of central nervous system infection.
AB  - OBJECTIVE: Cerebrospinal fluid (CSF) examination is mandatory whenever central
      nervous system (CNS) infection is suspected. However, pleocytosis is not detected
      in a substantial number of suspected patients who undergo CSF examination. This
      study aimed to identify parameters that can aid in predicting negative CSF
      examination results (defined as a white blood cell count of <5 cells/high-power
      field). METHODS: The study included 101 neurologically intact patients who
      underwent lumbar puncture because of suspicion of CNS infection. Patients were
      divided into negative and positive CSF examination groups, and their initial
      blood tests were comparatively analyzed. RESULTS: The negative group had a
      significantly higher proportion of neutrophils in white blood cells (81.5% vs.
      75.8%, P=0.012), lower proportion of lymphocytes in white blood cells (9.3% vs.
      16.7%, P=0.001), a higher neutrophil-to-lymphocyte ratio (9.1 vs. 4.4, P=0.001),
      a lower lymphocyte-to-monocyte ratio (1.6 vs. 2.4, P=0.008), and a higher C
      reactive protein level (21.0 vs. 5.0 mg/L, P<0.001) than the positive group. In
      the receiver-operating characteristic analysis, neutrophil-to-lymphocyte ratio
      and C-reactive protein had an area under the curve of >0.7, and the best cutoff
      values were 6.0 (accuracy 70.3%) and 12.7 mg/L (accuracy 76.2%), respectively.
      CONCLUSION: The neutrophil-to-lymphocyte ratio >=6 and C-reactive protein level
      >=12.7 mg/L was significantly associated with negative CSF examination result.

PMID- 28435900
TI  - Characteristics of orbital wall fractures in preschool and school-aged children.
AB  - OBJECTIVE: This study aimed to evaluate the injury patterns in pediatric patients
      with an orbital wall fracture (OWF) and to identify the differences in injury
      patterns between preschool and school-aged patients with OWF who presented to the
      emergency department. METHODS: We performed a retrospective observational study
      in the emergency department of a tertiary hospital between January 2004 and March
      2014. A total of 177 pediatric patients (<18 years) with OWF who underwent facial
      bone computed tomography scans with specific discharge codes were included.
      Patients were categorized into preschool (<=7 years) and school-aged (>7 years)
      pediatric groups. RESULTS: The inferior wall was the most common fracture site in
      both the preschool and school-aged pediatric groups (50.0% vs. 64.4%, P=0.15).
      The male-to-female ratio and the mechanism of injury showed significant
      differences between the two age groups. Violence was the most common mechanism of
      injury in the school-aged pediatric group (49.3%), whereas falls from a height
      caused OWF in approximately half of the patients in the preschool pediatric group
      (42.9%). Concomitant injuries and facial fractures had a tendency to occur more
      frequently in the school-aged pediatric group. CONCLUSION: Significant
      differences according to the sex and mechanisms of injury were identified in
      preschool and school-aged pediatric patients with OWF.

PMID- 28435901
TI  - Changes in electrocardiographic findings after closed thoracostomy in patients
      with spontaneous pneumothorax.
AB  - OBJECTIVE: We aimed to describe electrocardiographic (ECG) findings in
      spontaneous pneumothorax patients before and after closed thoracostomy. METHODS:
      This is a retrospective study which included patients with spontaneous
      pneumothorax who presented to an emergency department of a tertiary urban
      hospital from February 2005 to March 2015. The primary outcome was a difference
      in ECG findings between before and after closed thoracostomy. We specifically
      investigated the following ECG elements: PR, QRS, QTc, axis, ST segments, and R
      waves in each lead. The secondary outcomes were change in ST segment in any lead
      and change in axis after closed thoracostomy. RESULTS: There were two ECG
      elements which showed statistically significant difference after thoracostomy.
      With right pneumothorax volume of greater than 80%, QTc and the R waves in aVF
      and V5 significantly changed after thoracostomy. With left pneumothorax volume
      between 31% and 80%, the ST segment in V2 and the R wave in V1 significantly
      changed after thoracostomy. However, majority of ECG elements did not show
      statistically significant alteration after thoracostomy. CONCLUSION: We found
      only minor changes in ECG after closed thoracostomy in spontaneous pneumothorax
      patients.

PMID- 28435902
TI  - Emergency medical service personnel need to improve knowledge and attitude
      regarding prehospital sepsis care.
AB  - OBJECTIVE: We aimed to evaluate the knowledge and attitudes of emergency medical
      service (EMS) personnel pertaining to sepsis. We also compared EMS personnel's
      knowledge of sepsis and their intention to engage in prehospital sepsis
      management. METHODS: The survey was conducted during education conferences for
      EMS personnel in December 2013 and January 2015 in Seoul, Korea. The
      questionnaire composed of 10 questions relevant to sepsis, was distributed on
      scene, and was retrieved by investigators after the conference. We classified
      subjects into active and passive groups based on intent to participate in
      prehospital sepsis care. RESULTS: A total of 271 questionnaires were distributed;
      255 EMS personnel (94%) completed the survey, 126 (49%) of whom were first-degree
      emergency medical technicians (EMTs). Less than 75% of subjects provided
      clinically relevant responses to questions about the definitions of sepsis,
      tachycardia, tachypnea, hypotension, hypothermia, fluid resuscitation, and
      vasopressor. Only 15% of participants had suspected that a patient had sepsis,
      and 9% reported that they could identify patients with sepsis during
      transportation. Overall, first-degree EMTs showed higher levels of knowledge and
      a positive attitude to sepsis compared with non-first-degree EMTs. Sixty percent
      of the participants reported that they were actively involved in prehospital
      sepsis care. The active group showed significantly higher levels of knowledge and
      more positive responses to the clinical impact of prehospital sepsis care.
      CONCLUSION: Our study showed that is a substantial portion of EMS personnel lacks
      appropriate level of knowledge on sepsis care. We also found that the intention
      to engage in sepsis management was associated with appropriate knowledge of
      sepsis.

PMID- 28435903
TI  - Non-aneurysmal and non-traumatic subarachnoid hemorrhage after attempted suicide
      by incomplete hanging.
AB  - Hanging is a common method of suicide that is being reported more frequently in
      many countries. Several complications including injuries to the cervical spine,
      neck vessels, and brain can occur after attempted suicide by hanging. There are
      only a few reports of brain computed tomography and magnetic resonance imaging of
      hanging victims. The most common abnormality was diffuse cerebral edema. A
      subarachnoid hemorrhage is an atypical complication by suicidal hanging. We
      report a case of a female patient who presented to an emergency department with
      altered mental status after attempting suicide by incomplete hanging. The patient
      was diagnosed with a non-aneurysmal and non-traumatic subarachnoid hemorrhage.
      This case shows that spontaneous subarachnoid hemorrhage can develop due to a
      sudden elevation of intracranial pressure, as occurs with hanging.

PMID- 28435904
TI  - Spontaneous elbow hemarthrosis identified by point-of-care ultrasound.
AB  - Traumatic or spontaneous hemarthroses are an important cause of joint effusions,
      and can complicate innate or acquired coagulopathies. The elbow is an unusual
      location for a spontaneous hemarthrosis; we describe a previously unreported case
      of warfarin-induced spontaneous elbow hemarthrosis, diagnosed by point-of-care
      ultrasound. On the basis of clinical and ultrasound findings arthrocentesis was
      deferred, and the patient was successfully treated with warfarin reversal and
      conservative care. Physical examination is unreliable for the detection of a
      joint effusion, and misdiagnosis and can lead to unnecessary investigation or
      resource use. Point-of-care ultrasound allows accurate, prompt, direct
      visualization of a joint effusion, and non-invasive confirmation of a
      hemarthrosis. Ultrasound can facilitate accurate diagnosis and characterization
      of joint effusions to improve the care of patients with coagulopathy.

PMID- 28435905
TI  - Transurethral Resection of the Prostate, Bladder Explosion and Hyponatremic
      Encephalopathy: A Rare Case Report of Malpractice.
AB  - We present an original case report of a bladder explosion during a TURP
      intervention for benign prostatic hypertrophy, that was brought on by the
      absorption of about 5 liters of glycine 1.5% and then onset of a severe
      hyponatremia. The quick and inappropriate correction of this electrolyte
      imbalance led the onset of encephalopathy and the death of the patient. The
      authors discuss the pathogenesis of these uncommon diseases and, considering the
      most recent Italian Legislation, they highlight the importance to respect good
      clinical practice standards and guidelines to ensure the most appropriate
      treatments for the patient and remove any assumptions of medical liability.

PMID- 28435908
TI  - Development of a Japanese encephalitis virus-like particle vaccine in silkworms
      using codon-optimised prM and envelope genes.
AB  - We have successfully prepared a Japanese encephalitis virus (JEV) - Nakayama
      virus like particle (NVLP) vaccine using synthetic codon-optimized prM and E
      genes. The expression of the recombinant JEV Nakayama-BmNPV (JEV-NNPV) virus was
      determined in infected silkworm Bm-N cells by fluorescence and Western blot
      analysis. The recombinant was inoculated into silkworm pupae and the yield of
      Nakayama VLP (NVLP) reached a peak in the homogenates after 3 days. Additionally,
      in the peptide analysis of infected pupae homogenate, it appeared approximately
      300-500 MUg E protein/pupa were produced. When purified the above eluates on the
      discontinuous sucrose density gradient centrifugation, NVLP showed a strong
      hemagglutination (HA) activity by using chicken red blood cell in phosphate
      buffered saline (PBS) free from Mg++ and Ca++ ions. The immune antisera against
      NVLP strain could efficiently neutralize the plaque formation of Nakayama,
      Beijing-1 and Muar strains, showing tendency of much higher reaction with
      heterologous Muar strain than homologous Nakayama strain. Our findings suggest
      that the JEV-NVLP may be useful for JEV epidemic control in many endemic areas of
      Asian countries as a widely effective and less expensive JE vaccine.

PMID- 28435907
TI  - Modeling Tumor Clonal Evolution for Drug Combinations Design.
AB  - Cancer is a clonal evolutionary process. This presents challenges for effective
      therapeutic intervention, given the constant selective pressure towards drug
      resistance. Mathematical modeling from population genetics, evolutionary
      dynamics, and engineering perspectives are being increasingly employed to study
      tumor progression, intratumoral heterogeneity, drug resistance, and rational drug
      scheduling and combinations design. In this review, we discuss promising
      opportunities these inter-disciplinary approaches hold for advances in cancer
      biology and treatment. We propose that quantitative modeling perspectives can
      complement emerging experimental technologies to facilitate enhanced
      understanding of disease progression and improved capabilities for therapeutic
      drug regimen designs.

PMID- 28435909
TI  - Self-assembled particulate PsaA as vaccine against Streptococcus pneumoniae
      infection.
AB  - Streptococcus pneumoniae is a human pathogen responsible for the majority of
      childhood pneumonia and media otitis cases worldwide. The diversity of its
      capsular polysaccharides (CPS) results in more than 91 serotypes of which at
      least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are
      currently licensed and provide protection against the infection caused by the
      respective serotypes but not against new and emerging virulent serotypes. In this
      study, we considered the conserved protein antigen PsaA, the pneumococcal surface
      adhesin A, in order to overcome the limitations of CPS antigens. The PsaA was
      translationally fused to a polyhydroxybutyrate (PHB) synthase which mediated
      production of PsaA displayed on PHB inclusions in recombinant Escherichia coli.
      This suggested that the PsaA fusion to the PHB synthase did not interfere with
      PHB synthase activity and its ability to mediate formation of nano-sized
      inclusions composed of a PHB core surrounded by the PHB synthase fused to PsaA.
      Isolated PHB beads showed a negative surface charge. Transmission electron
      microscopy analysis suggested that the PsaA fusion to the PHB synthase reduced
      the size of PHB beads from about 500 nm to 100 nm. The integrity and antigenicity
      of the fusion protein attached to isolated PHB beads was confirmed by SDS-PAGE,
      tryptic peptide fingerprinting analysis using MALDI-TOF-MS/MS and immunoblotting
      using a monoclonal anti-PsaA antibody. Mice immunized with PsaA displaying PHB
      beads produced high and specific IgG levels dominated by IgG1 isotype. While IgG1
      titer were similar between soluble and insoluble PsaA, the IgG2 titers were
      strongly increased upon vaccination with insoluble PsaA i.e. PsaA displayed on
      PHB beads. Particulate PsaA-PHB beads elicited IgG antibodies recognizing PsaA in
      whole cell lysates of seven different serotypes of S. pneumoniae. This study
      suggested that PHB beads are suitable carriers for PsaA in order to induce a
      significant and specific Th-2-type immune response.

PMID- 28435910
TI  - March 2017, JSS.

PMID- 28435911
TI  - Is cell salvage cost-effective in posterior arthrodesis for adolescent idiopathic
      scoliosis in the public health system?
AB  - BACKGROUND: To evaluate the efficacy and cost-effectiveness of cell salvage (CS)
      in reducing allogeneic transfusion in patients undergoing surgery for idiopathic
      scoliosis. METHODS: A case-control study with 42 patients with adolescent
      idiopathic scoliosis (AIS), submitted to posterior arthrodesis with
      instrumentation from 8/2008 to 12/2014 at the General Hospital of Fortaleza,
      Brazil. CS was used in 27 patients and not used in 15. The data was processed
      using the SPSS 20.0. The confidence level was 0.05. RESULTS: There were no
      significant differences between the groups for the variables of age, sex,
      preoperative weight, postoperative blood drainage, and surgical time. There was a
      significant reduction in the intra-operative allogeneic transfusion in the case
      group compared to the control; there was no significant difference in the
      postoperative period. Adding the two periods together there was a significant
      difference with less allogeneic red blood cells (RBC) transfused in the CS group.
      The total cost of allogeneic RBC between the intra and postoperative groups was
      higher in the control group (P=0.01). Due to this difference ($350.00-$136.93)
      the cost was $213.07. The net savings were $213.07. Multiplying this by the 27
      subjects, allogeneic RBC transfusion led to a cost reduction of $5,752.89 for the
      State. CONCLUSIONS: The CS was effective in reducing allogeneic transfusion
      during surgery and in the total period that AIS patients underwent surgery it was
      also cost-effective.

PMID- 28435906
TI  - Low back pain in older adults: risk factors, management options and future
      directions.
AB  - Low back pain (LBP) is one of the major disabling health conditions among older
      adults aged 60 years or older. While most causes of LBP among older adults are
      non-specific and self-limiting, seniors are prone to develop certain LBP
      pathologies and/or chronic LBP given their age-related physical and psychosocial
      changes. Unfortunately, no review has previously summarized/discussed various
      factors that may affect the effective LBP management among older adults.
      Accordingly, the objectives of the current narrative review were to
      comprehensively summarize common causes and risk factors (modifiable and non
      modifiable) of developing severe/chronic LBP in older adults, to highlight
      specific issues in assessing and treating seniors with LBP, and to discuss future
      research directions. Existing evidence suggests that prevalence rates of severe
      and chronic LBP increase with older age. As compared to working-age adults, older
      adults are more likely to develop certain LBP pathologies (e.g., osteoporotic
      vertebral fractures, tumors, spinal infection, and lumbar spinal stenosis).
      Importantly, various age-related physical, psychological, and mental changes
      (e.g., spinal degeneration, comorbidities, physical inactivity, age-related
      changes in central pain processing, and dementia), as well as multiple risk
      factors (e.g., genetic, gender, and ethnicity), may affect the prognosis and
      management of LBP in older adults. Collectively, by understanding the impacts of
      various factors on the assessment and treatment of older adults with LBP, both
      clinicians and researchers can work toward the direction of more cost-effective
      and personalized LBP management for older people.

PMID- 28435912
TI  - One and two level posterior lumbar interbody fusion (PLIF) using an expandable,
      stand-alone, interbody fusion device: a VariLift(r) case series.
AB  - BACKGROUND: Surgical interventions such as posterior lumbar interbody fusion
      (PLIF) with and without posterior instrumentation are often employed in patients
      with degenerative spinal conditions that fail to respond to conservative medical
      management. The VariLift(r) Interbody Fusion System was developed as a stand
      alone solution to provide the benefits of an intervertebral fusion device without
      the requirement of supplemental pedicle screw fixation. METHODS: In this
      retrospective case series, 25 patients underwent PLIF with a stand-alone
      VariLift(r) expandable interbody fusion device without adjunctive pedicle screw
      fixation. There were 12 men and 13 women, with a mean age of 57.2 years (range,
      33-83 years); single level in 18 patients, 2 levels in 7 patients. Back pain
      severity was reported as none, mild, moderate, severe and worst imaginable at
      baseline, 6 and 12 months. Preoperatively, 88% (22 of 25) of patients reported
      severe back pain. RESULTS: All patients experienced symptomatic improvement and,
      by 12 months postoperatively, 71% (15 of 21) of patients reported only mild
      residual pain. Overall, pain scores improved significantly from baseline to 12
      months (P=0.0002). There were no revision surgeries and fusion was achieved 12 of
      13 patients (92%) who returned for a 12-month radiographic follow-up. There were
      three cases of intractable postsurgical pain which required extended
      hospitalization or pain management, one wound infection and one case of surgical
      site dehiscence, both treated and resolved during inpatient hospitalization.
      CONCLUSIONS: In this single-physician case series, the VariLift(r) device used in
      single or two-level PLIF provided effective symptom relief and produced a high
      fusion rate without the need for supplemental fixation.

PMID- 28435913
TI  - A prospective clinical study comparing MI-TLIF with unilateral versus bilateral
      transpedicular fixation in low grade lumbar spondylolisthesis.
AB  - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF)
      has become one of the standard techniques for approaching ipsilateral
      decompression, anterior column fusion, and posterior stabilization. This
      procedure is usually accompanied by the placement of bilateral transpedicular
      screws in the corresponding segment. The purpose of this study was to evaluate
      the clinical efficacy of unilateral screw fixation compared with bilateral
      fixation in patients diagnosed with low-grade symptomatic lumbar
      spondylolisthesis who underwent an MI-TLIF technique. METHODS: A prospective and
      comparative study was performed in 67 patients with grade 1 symptomatic lumbar
      spondylolisthesis. The sample was allocated on both unilateral fixation group
      (n=33) and bilateral fixation group (n=34). Clinical outcomes were evaluated
      using Oswestry Disability Index (ODI), visual analogue scale (VAS) for leg and
      back pain, and Short Form 36 Health Survey (SF-36), preoperatively, and at 1, 3,
      6, and 12 months postoperatively. Changes over time and differences between the
      groups were analyzed. Statistical analyses included: Friedman test, Student's t
      test and Mann-Whitney's U. A two-tailed P value of <0.05 was considered
      significant. RESULTS: During 1-year of evaluation there were no significant
      clinical differences between both groups. CONCLUSIONS: Patients with grade 1
      symptomatic lumbar spondylolisthesis treated with MI-TLIF with unilateral screw
      fixation had similar clinical results than those treated with bilateral fixation
      at 12 months postoperatively.

PMID- 28435914
TI  - Factors predictive of topographical accuracy in spine level localization.
AB  - BACKGROUND: Pre-operative spine level localization by palpation of anatomical
      landmarks (ribs, spinous processes) in posterior approaches for surgeries from T4
      to L2 is often inaccurate. This can lead to ineffective utilization of procedural
      time, increased radiation dose, potentially longer skin incision and wrong level
      surgery. Factors affecting topographical accuracy includes body mass index (BMI)
      of the patient, congenital or acquired deformity and knowledge of topographical
      anatomy. METHODS: All patients had the presumed location of their pathology
      marked on the skin using anatomical landmarks prior to application of the Target
      Tape(r) (Vancouver, BC, Canada) and verification using an anterior-posterior
      radiograph. Potential factors predictive of accurate pre-operative spine level
      localization such as age, gender, BMI, palpable deformity, pathology related
      interspinous distance (ISPD) and pathology related skin to spinous process
      distance were evaluated. RESULTS: A prospective study was performed with 30
      consecutive patients undergoing posterior spine surgery (T4 to L2). Accuracy of
      pathology related spine level localization using anatomical landmarks was only
      40%. Pathology related ISPDs of more than 10 mm and palpable deformity was
      significantly correlated with successful determination of spine levels using
      anatomical landmarks. CONCLUSIONS: This study showed that poor spine level
      localization using anatomical landmarks was associated with pathology related
      ISPDs of less than 10 mm. Conversely, patients with palpable spinal deformity
      have their levels easily localized.

PMID- 28435915
TI  - Impact of surgical approach on complication rates after elective spinal fusion
      (>=3 levels) for adult spine deformity.
AB  - BACKGROUND: While there are variations in techniques and surgical approaches to
      spinal fusion, there is not a defined consensus on a recommended surgical
      approach. The aim of this study is to determine if there was a difference in
      intra- and post-operative complication rates between different surgical
      approaches after elective spinal fusion (>=3 levels) for adult spine deformity.
      METHODS: The medical records of 443 adult spine deformity patients undergoing
      elective spinal fusion (>=3) at a major academic institution from 2005 to 2015
      were reviewed. We identified 96 (21.7%) anterior only, 225 (50.8%) posterior
      only, and 122 (27.5%) combined anterior/posterior approaches taken for spinal
      fusion (anterior: n=96; posterior: n=225). Patient demographics, comorbidities,
      anatomical location, and complication rates were collected for each patient. The
      primary outcome investigated in this study was the rate of intra- and post
      operative complications. RESULTS: Patient demographics and comorbidities were
      similar between all groups. The posterior approach had significantly higher EBL
      (P<0.0001) and number of PRBC blood transfusions (P<0.002), while the combined
      approach had a higher operative time (P<0.0001). The posterior approach had a
      significantly higher rate of intraoperative durotomies than anterior and combined
      (anterior: 0% vs. posterior: 11.1% vs. combined: 4.1%, P<0.0001). There was no
      significant difference in the rate 30-day readmissions between the cohorts
      (anterior: 10.4% vs. posterior: 12.8% vs. combined: 13.1%, P=0.80). CONCLUSIONS:
      Our study suggests that posterior approaches to spinal fusion may lead to a
      higher incidence of complications compared to anterior or combined
      anterior/posterior approaches.

PMID- 28435916
TI  - Feasibility of endoscopic discectomy by inter laminar approach at a high volume
      tertiary public hospital in a developing country.
AB  - BACKGROUND: Surgical treatment for lumbar disc herniation consists of discectomy
      performed either open or minimally invasive techniques. Endoscopic discectomy
      using the tubular retractor is been increasingly used as it gives advantage of
      smaller incision, less tissue injury and faster recovery. The aim of this study
      was to check its feasibility and learning curve at a tertiary public sector
      hospital with a large volume load (more than 50 spine surgeries per month) with
      treatment provided free of cost. METHODS: Eighty patients underwent endoscopic
      discectomy using tubular retractor were prospectively followed for a period of 12
      months. All patients included were having disc herniation at a single level after
      appropriate conservative trial of 6 weeks. Patients with segmental instability or
      previous spine surgery were excluded. All were operated by a single senior
      orthopaedic surgeon. Duration of surgery, blood loss, and day of mobilization,
      complications and duration of hospitalisation were noted. VAS for pain, Oswestry
      Disability Index, SF 12 and modified MacNab criteria were used to assess the
      functional outcome. RESULTS: Mean age of patients was 34.9 years (range 17 to 72
      years) with sex ratio of 2.6:1. The mean VAS score improved from 8 to 1.1,
      Oswestry Disability Index from 52 to 20 and SF 12 scores (MCS/PCS) from 34/43 to
      49.2/56. According to modified MacNab criteria there were 77.5% excellent, 13.75%
      good, 7.5% fair and 1.25% poor cases. Average surgical duration was 48.75 min and
      blood loss was 32.13 mL. There were 3 dural tears, 1 infection, 2 recurrences and
      1 sensory radiculopathy. CONCLUSIONS: Endoscopic discectomy using tubular
      retractor has a potential to become a gold standard in catering this patient
      groups. It has great feasibility and shows equivalent results to all other
      techniques with lesser learning curve being an added advantage.

PMID- 28435917
TI  - Effect of employment status on length of hospital stay, 30-day readmission and
      patient reported outcomes after spine surgery.
AB  - BACKGROUND: Growing scrutiny has placed hospitals at the center of readmission
      prevention. The relationship between pre-operative employment status, length of
      hospital stays (LOS) and 30-day readmission rates after elective spine surgery
      remains unclear. METHODS: The medical records of 360 patients (employed: n=174,
      unemployed: n=70, retired: n=40, disabled: n=76) undergoing elective spine
      surgery at a major academic medical center were reviewed. Patient demographics,
      comorbidities, and post-operative complication rates were recorded. All patients
      had comprehensive 1-year patient reported outcomes (PROs) measures. We
      hypothesized that employment status is associated with decreased LOS and
      decreased risk of 30-day readmission after elective spine surgery. All-cause
      readmissions within 30 days of discharge was the primary outcome variable.
      RESULTS: Baseline characteristics were similar in all cohorts. There was no
      difference in operative time, estimated blood loss (EBL), or number of fusion
      levels between all patient cohorts. There were no significant differences in peri
      operative complication rates between patient cohorts. On average, the LOS was
      shorter for the employed compared to non-employed patients (4.89 vs. 5.26 days).
      The rate of 30-day readmission was 2-fold greater unemployed compared to employed
      patients (5.17% vs. 10%). At 1-year after surgery, employed patients were more
      likely to express functional improvement (change in ODI score) compared to
      unemployed patients (ODI: employed: 33.80 vs. unemployed: 41.93). CONCLUSIONS:
      Our study suggests that employment status may be associated with shorter duration
      of hospital stay, lower 30-day readmission rates and greater functional
      improvement. Future interventions to reduce unplanned hospital readmissions
      should consider pre-operative employment status.

PMID- 28435919
TI  - Spontaneous spinal epidural hematoma: literature review.
AB  - Review the current literature regarding spontaneous spinal epidural hematomas
      (SSEHs) and report on the known risk factors, evaluation, and treatment of this
      rare entity. A literature search was performed using PubMed and Ovid to identify
      articles pertaining to SSEHs. Due to the rarity of the pathologic entity, only
      scattered case reports and associated reviews are available. SSEHs are a rare yet
      potentially life-altering event. The underlying risk factors are poorly
      understood, and SSEHs present with minimal or no antecedent trauma. SSEHs warrant
      urgent surgical intervention given the associated risk of permanent neurologic
      sequelae. Given the potential for persistent neurologic deficits, physicians must
      entertain a clinical suspicion of SSEH when a patient presents with a history of
      back pain followed by neurologic deficits. Even without clear risk factors for
      hemorrhage, the appropriate evaluation to include advanced imaging studies should
      be obtained to allow for identification of this entity and urgent surgical
      management.

PMID- 28435918
TI  - Cost analysis of adolescent idiopathic scoliosis surgery: early discharge
      decreases hospital costs much less than intraoperative variables under the
      control of the surgeon.
AB  - BACKGROUND: Spinal fusion surgery for the treatment of adolescent idiopathic
      scoliosis (AIS) is increasing. Health systems and surgeons are decreasing
      hospital length of stay (LOS) to decrease costs. The purpose of this study was to
      review the contribution of an accelerated discharge protocol on the total cost of
      a single episode of care related to the surgical treatment of AIS at a single
      institution. METHODS: A retrospective cost analysis was performed over an 18
      month period, from January 2014 through June 2015, before and after the
      institution of an accelerated discharge program. Patients treated surgically with
      ICD-9 code 737.30 (Idiopathic Scoliosis) were reviewed. Itemized costs and LOS
      were analyzed collectively and by surgeon before and after the accelerated
      discharge protocol. RESULTS: Eighty AIS patients were treated surgically. The
      accelerated discharge program significantly reduced average LOS from 4.2 days in
      2014 to 3.3 days during the first 6 months of 2015 (P<=0.05). There were no
      increases in complications. There was a 9% decrease in the total average costs
      per episode of care. A weighted average, a relative average change in costs, and
      an average cost savings per case were calculated for 12 different categories.
      Average Surgical Services and Nursing costs decreased during the study period
      while all other costs increased. The accelerated discharge program did not
      directly contribute significantly to this decrease in costs. Greatest cost
      reduction was associated with average bone graft and pedicle screw cost, with an
      overall 8.5% reduction in pedicle screw use and a 58% reduction in bone graft
      costs. CONCLUSIONS: Intraoperative variables under the direct control of the
      surgeon contribute much more to cost reduction than an accelerated discharge
      program for surgically treated AIS patients.

PMID- 28435920
TI  - Microscopy-assisted interspinous tubular approach for lumbar spinal stenosis.
AB  - Various minimally invasive techniques have been reported as an alternative to
      conventional lumbar decompression. The major advantage of these minimally
      invasive procedures lies in their reduction of unnecessary exposure and tissue
      trauma. Our objective was to describe a minimally invasive procedure for lumbar
      spinal stenosis decompression by enlarging the lumbar interspinous space,
      approaching it with a tubular retractor, and assisting with microscopy.
      Thoracolumbar fascia and paravertebral muscles are preserved throughout the whole
      procedure. Iatrogenic instability of the spine can be avoided if during the
      procedure both joints are just undercut in order to decompress the subarticular
      space. The approach described in this manuscript could be used as an alternate
      minimally invasive surgical procedure for the treatment of central and lateral
      lumbar spinal stenosis.

PMID- 28435921
TI  - Technical note: unilateral hemilaminotomy for intradural lesions (UHIL).

PMID- 28435922
TI  - Spontaneous corpectomy and anterior arthrodesis in lumbar spine: how Ankylosing
      Spondylitis can resolve a vertebral fracture.
AB  - Between the 80% and 90% of vertebral fractures in over 65 years people are due to
      osteoporosis. Over the 30% of patients affected by vertebral osteoporosis
      fractures needs of surgical treatment and the 12% presents complications
      requiring an invasive surgical approach. We report an unusual case of spontaneous
      corpectomy and anterior arthrodesis occurred in a patient suffering from
      Ankylosing Spondylitis. This event invites us to reflect about the magnitude of
      the biological power of the bone healing, even in adverse conditions.

PMID- 28435923
TI  - Bone bridge formation across the neuroforamen 14 years after instrumented fusion
      for isthmic spondylolisthesis-a case report.
AB  - This case report describes the first case of a bone bridge formation across the
      left L5/S1 neuroforamen after instrumented posterolateral fusion for L5/S1
      isthmic spondylolisthesis. Our patient was a 70-year-old lady who had grade 2,
      L5/S1 isthmic spondylolisthesis and bilateral S1 nerve root compression. She
      suffered from mechanical low back pain and neurogenic claudication, with
      radicular pain over both S1 dermatomes. She underwent in-situ, instrumented,
      posterolateral fusion and was asymptomatic for more than 13 years before
      developing progressive onset of left radicular pain over the L5 dermatome.
      Imaging revealed a bisected left L5/S1 neuroforamen secondary to a bone bridge
      formation resulting in stenosis. The pars defect in this case may have had
      sufficient osteogenic and osteoinductive factors to heal following spinal
      stabilization. Although in-situ posterolateral fusion is an accepted surgical
      treatment for isthmic spondylolisthesis, surgeons should consider reduction of
      the spondylolisthesis and excision of the pars defects to avoid this possible
      long-term complication.

PMID- 28435924
TI  - Treatment of chronic traumatic C7-T1 grade III spondylolisthesis with mild
      neurological deficit: case report.
AB  - Traumatic cervical severe spondylolisthesis is a rare and severe lesion which is
      typically associated with a spinal cord injury. Nevertheless, it occasionally has
      a pauci-symptomatic course which may delay its diagnosis. The authors report an
      exceptional case of a 33-year-old woman who had mild spasticity in her lower
      limbs and neck pain 9 months after a traffic accident. The computed tomographic
      scan and magnetic resonance image revealed C7-T1 grade III spondylolisthesis and
      spinal cord signal change. The initial cervical traction did not obtain a spinal
      realignment. An anterior-posterior approach was performed to achieve a correct
      spinal fusion. After 18 months of follow-up care, the patient's symptoms improved
      significantly and she began to lead a normal life again. The case underlines the
      importance of performing a correct initial diagnostic workup upon a patient. This
      would improve surgical management by avoiding a worsening of the initial
      neurological deficit during the realignment maneuvers in the chronic grade III,
      IV or V spondylolisthesis.

PMID- 28435925
TI  - Distal junctional failure secondary to L5 vertebral fracture-a report of two rare
      cases.
AB  - Distal junctional failure (DJF) with fracture at the last instrumented vertebra
      is a rare occurrence. In this case report, we present two patients with L5
      vertebral fracture post-instrumented fusion of the lumbar spine. The first
      patient is a 78-year-old female who had multi-level degenerative disc disease,
      spinal stenosis and degenerative scoliosis involving levels T12 to L5. She
      underwent instrumented posterolateral fusion (PLF) from T12 to L5, and
      transforaminal lumbar interbody fusion (TLIF) at L2/3 and L4/5. Six months after
      her operation, she presented with a fracture of the L5 vertebral body
      necessitating revision of the L5 pedicle screws, with additional TLIF of L5/S1.
      The second patient is a 71-year-old female who underwent decompression and TLIF
      of L3/4 and L4/5 for degenerative spondylolisthesis. Six months after the
      surgery, she developed a fracture of the L5 vertebral body with loosening of the
      L5 screws. The patient declined revision surgery despite being symptomatic. DJF
      remains poorly understood as its rare incidence precludes sufficiently powered
      studies within a single institution. This report aims to contribute to the
      currently scarce literature on DJF.

PMID- 28435926
TI  - Lumbar disc herniation presenting with contralateral symptoms: a case report.
AB  - Lumbar disc herniation is common and may be symptomatic. The magnetic resonance
      imaging (MRI) scan is an appropriate tool to confirm the diagnosis and affected
      level of the spine. While a disc herniation is usually associated with
      ipsilateral symptoms, a few cases have been reported to present with
      contralateral symptoms. We report a unique case of left lumbar disc herniation at
      L5/S1 who presented with contralateral symptoms and was successfully treated with
      a right L5/S1 foraminal block. However, the patient developed concordant
      ipsilateral symptoms 6 weeks later and was treated with left L5/S1
      microdiscectomy.

PMID- 28435927
TI  - Traumatic dislocation of the S1 polyaxial pedicle screw head: a case report.
AB  - Polyaxial screw head dislocation in the absence of a manufacture defect is
      extremely rare and represents a biomechanical overload of the screw, leading to
      early failure. A 58-year-old gentleman underwent instrumented fusion using
      polyaxial pedicle screws-titanium rod construct with interbody cage for
      spondylolytic spondylolisthesis at the L5/S1 level. He attempted to bend forward
      ten days after the surgery which resulted in a dislocation of the right S1
      polyaxial screw head from the screw shank with recurrence of symptoms. He
      underwent revision surgery uneventfully. This case highlights the need to pay
      particular attention to the strength of fixation and the amount of release to
      avoid such a complication.

PMID- 28435929
TI  - Megacolon as an atypical presentation of cervical myelopathy.
AB  - A 61-year-old gentleman was admitted with progressive symptoms of cervical
      myelopathy. An MRI performed showed severe compression from C3-6 with cord signal
      changes. He was offered surgical intervention but the operation had to be delayed
      because of worsening abdominal distension. X-rays performed showed a severely
      dilated colon measuring >12 cm. A CT did not show any obstructive cause. He was
      managed conservatively for more than 2 weeks but did not improve. As his symptoms
      continued to worsen, a decision was made to proceed with a C3-6 posterior
      decompression and fusion, despite the theoretical risk of bacterial translocation
      predisposing him to infection. Postoperatively, he improved significantly.
      Interestingly, his abdominal distention had also improved and a repeat X-ray
      showed complete resolution of the megacolon. In conclusion, this case highlights
      that long standing cervical cord compression may be a cause for an "atonic"
      megacolon. Once all causes of intestinal obstruction are excluded, surgical
      decompression of the cervical stenosis should proceed, and need not be delayed
      for the megacolon resolve spontaneously.

PMID- 28435928
TI  - Extra-skeletal Ewing sarcoma of the lumbosacral region in an adult pregnant
      patient: a case report.
AB  - Extra-skeletal Ewing sarcoma in pregnancy is rare. There is thus limited
      scientific evidence to guide clinicians in its complicated management,
      particularly within the context of early gestation. We therefore share our
      successful outcome in a 32-year-old pregnant patient, following a unique
      management strategy of complete aggressive surgical resection prior to neo
      adjuvant therapy. The case involved a 2-month history of right-sided back and
      gluteal pain, with associated paraesthesia. Lumbosacral magnetic resonance
      imaging (MRI) revealed an approximate 40*50 mm indeterminate mass in the lower
      right paraspinal musculature. The mass extended into the first right sacral
      foramen and the central canal; and also impinged on the S2 exiting nerve. After
      considering the patients' rapid deterioration, pregnant status and other clinical
      factors, it was elected to proceed with complete surgical resection prior to any
      other therapeutic modality. Following surgery, the patient experienced immediate
      resolution of her pain and by 6 weeks was able to cease the use of all
      analgesics. At 32-weeks' gestation she underwent an uncomplicated vaginal
      delivery. At 9 months follow up, she remains disease free and has experienced
      complete resolution of her back pain and radiculopathy.

PMID- 28435930
TI  - Spinal subdural hematoma: a rare case of spinal subdural hematoma complicating
      routine, minimally invasive lumbar discectomy and decompression and relevant
      literature review.
AB  - We present a case of apparently uncomplicated lumbar decompression and discectomy
      with delayed postoperative neurological deterioration secondary to subdural
      hematoma at the thoracolumbar level of the spinal cord. Previously described
      subdural hematomas have occurred spontaneously or related to iatrogenic injury.
      Hitherto, no case of acute postoperative subdural hematoma has been reported in
      the postoperative setting in the absence of known iatrogenic dural injury. A 76
      year-old male with central and lateral recess spinal stenosis underwent
      apparently uncomplicated bilateral L3-4 and left sided L4-5 decompressive partial
      laminectomies and discectomy. No incidental dural injury or cerebrospinal fluid
      leak was detected. On postoperative day two, he developed progressive, profound
      weakness, sensory changes and urinary retention. Magnetic resonance imaging (MRI)
      demonstrated a compressive subdural fluid collection extending between T11-L2,
      which was confirmed to be xanthochromic and under pressure superficial to an
      undisturbed arachnoid at emergent surgical exploration and evacuation. The
      mechanism of this complication is unknown. The patient went on to a complete
      recovery following surgical evacuation of the fluid via durotomy. While this is a
      very rare event, it reminds that a high index of suspicion is required with a low
      threshold for urgent imaging and intervention in the postoperative period upon
      development of unexpected, progressive and/or profound neurological findings
      regardless of intraoperative course.

PMID- 28435931
TI  - Bone morphogenic proteins are a good choice for select spinal surgeries and merit
      further research.

PMID- 28435932
TI  - Default Mode Network Subsystems are Differentially Disrupted in Posttraumatic
      Stress Disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder
      characterized by debilitating re-experiencing, avoidance, and hyperarousal
      symptoms following trauma exposure. Recent evidence suggests that individuals
      with PTSD show disrupted functional connectivity in the default mode network, an
      intrinsic network that consists of a midline core, a medial temporal lobe (MTL)
      subsystem, and a dorsomedial prefrontal cortex (dMPFC) subsystem. The present
      study examined whether functional connectivity in these subsystems is
      differentially disrupted in PTSD. METHODS: Sixty-nine returning war Veterans with
      PTSD and 44 trauma-exposed Veterans without PTSD underwent resting state
      functional MRI (rs-fMRI). To examine functional connectivity, seeds were placed
      in the core hubs of the default mode network, namely the posterior cingulate
      cortex (PCC) and anterior medial PFC (aMPFC), and in each subsystem. RESULTS:
      Compared to controls, individuals with PTSD had reduced functional connectivity
      between the PCC and the hippocampus, a region of the MTL subsystem. Groups did
      not differ in connectivity between the PCC and dMPFC subsystem or between the
      aMPFC and any region within either subsystem. In the PTSD group, connectivity
      between the PCC and hippocampus was negatively associated with avoidance/numbing
      symptoms. Examination of the MTL and dMPFC subsystems revealed reduced
      anticorrelation between the ventromedial PFC (vMPFC) seed of the MTL subsystem
      and the dorsal anterior cingulate cortex in the PTSD group. CONCLUSIONS: Our
      results suggest that selective alterations in functional connectivity in the MTL
      subsystem of the default mode network in PTSD may be an important factor in PTSD
      pathology and symptomatology.

PMID- 28435933
TI  - The C677T variant in MTHFR modulates associations between brain integrity, mood,
      and cognitive functioning in old age.
AB  - INTRODUCTION: The C677T functional variant in the methylene-tetrahydrofolate
      reductase (MTHFR) gene leads to reduced enzymatic activity and elevated blood
      levels of homocysteine. Hyperhomocysteinemia has been linked with higher rates of
      cardiovascular diseases, cognitive decline, and late-life depression. METHODS AND
      MATERIALS: Here, 3D magnetic resonance imaging data was analyzed from 738
      individuals (age: 75.5 +/- 6.8 years; 438 men/300 women) including 173
      Alzheimer's patients, 359 subjects with mild cognitive impairment, and 206
      healthy older adults, scanned as part of the Alzheimer's Disease Neuroimaging
      Initiative (ADNI). RESULTS: We found that this variant associates with localized
      brain atrophy, after controlling for age, sex, and dementia status, in brain
      regions implicated in both intellectual and emotional functioning, notably the
      medial orbitofrontal cortices. The medial orbitofrontal cortex is involved in the
      cognitive modulation of emotional processes, and localized atrophy in this region
      was previously linked with both cognitive impairment and depressive symptoms.
      Here, we report that increased plasma homocysteine mediates the association
      between MTHFR genotype and lower medial orbitofrontal volumes, and that these
      volumes mediate the association between cognitive decline and depressed mood in
      this elderly cohort. We additionally show that vitamin B12 deficiency interacts
      with the C677T variant in the etiology of hyperhomocysteinemia. CONCLUSION: This
      study sheds light on important relationships between vascular risk factors, age
      related cognitive decline, and late-life depression, and represents a significant
      advance in our understanding of clinically relevant associations relating to
      MTHFR genotype.

PMID- 28435934
TI  - The Amblyopia Treatment Studies: Implications for Clinical Practice.

PMID- 28435935
TI  - Proliferative Vitreoretinopathy in Treated Retinoblastoma.
AB  - OBJECTIVE: To evaluate the clinical and histopathologic characteristics of
      patients who develop proliferative vitreoretinopathy after retinoblastoma
      treatment. DESIGN: Retrospective review of three cases of proliferative
      vitreoretinopathy (PVR) that developed after successful treatment of
      retinoblastoma from 2003 to 2015. SUBJECTS: Three patients with treated
      retinoblastoma who developed severe PVR and required enucleation. METHODS: Review
      of clinical charts, fundus drawings, Ret-Cam 3 images, and histopathology
      specimens. MAIN OUTCOME MEASURES: Clinical and histopathologic characterization
      of PVR in treated retinoblastoma. RESULTS: Three patients developed severe PVR
      after sequential thermal laser combined with systemic chemotherapy for
      retinoblastoma. At presentation patients were 6, 7, and 9 months of age, and all
      had bilateral retinoblastoma. Time to development of proliferative tissue was 9,
      12, and 20 months after initial treatment. Proliferation was characterized by
      progressive growth of white vascularized tissue with associated traction on the
      retina and sometimes hemorrhage. All patients underwent enucleation.
      Histopathologic evaluation revealed treated retinoblastoma tumor with a Type 3
      regression pattern, pre- and subretinal fibrovascular tissue consistent with PVR,
      and reactive changes in the retinal pigment epithelium. None of the patients
      developed recurrence of retinoblastoma or systemic metastasis. CONCLUSION: PVR
      uncommonly develops after successful treatment of retinoblastoma and may result
      in traction or rhegmatogenous retinal detachment along with vitreous hemorrhage.
      Early stages of proliferation may be difficult to distinguish from recurrent
      tumor. Enucleation may be required due to poor vision and inability to adequately
      monitor for tumor recurrence.

PMID- 28435936
TI  - The Effects of Learning and Retrieval Contexts on Cross-situational Word
      Learning.
AB  - Natural linguistic environments usually provide structured input, in that words
      that are semantically-related are likely to occur in the same situation. The
      current study examined whether this kind of semantically-themed structure
      facilitated cross-situational word learning. Results from two experiments
      consistently showed that participants had higher performance in semantically
      themed learning contexts. In contrast, themed retrieval contexts did not affect
      performance. Our work suggests that learners' ability to use statistical
      information to acquire word-to-object mappings is enhanced when learning is put
      in a more naturalistic and structured context.

PMID- 28435938
TI  - Obtaining effective rate coefficients to describe the decomposition kinetics of
      the corannulene oxyradical at high temperatures.
AB  - Unimolecular reactions play an important role in combustion kinetics. An
      important task of reaction kinetic analysis is to obtain the phenomenological
      rate coefficients for unimolecular reactions based on the master equation
      approach. In most cases, the eigenvalues of the transition matrix describing
      collisional internal energy relaxation are of much larger magnitude than and well
      separated from the chemically significant eigenvalues, so that phenomenological
      rate coefficients may be unequivocally derived for incorporation in combustion
      mechanisms. However, when dealing with unimolecular reactions for a large
      molecule, especially at high temperatures, the large densities of states of the
      reactant cause the majority of the population distribution to lie at very high
      energy levels where the microcanonical reaction rate constants are large and the
      relaxation and chemical eigenvalues overlap, so that well-defined
      phenomenological rate coefficients cannot be determined. This work attempts to
      analyze the effect of overlapping eigenvalues on the high-temperature kinetics of
      a large oxyradical, based on microcanonical reaction rates and population
      distributions as well as the eigenvalue spectrum of the transition matrix from
      the master equation. The aim is to provide a pragmatic method for obtaining the
      most effective rate coefficients for competing elimination, dissociation, and
      bimolecular reactions for incorporation in combustion mechanisms. Our approach is
      demonstrated with a representative example, thermal decomposition and H addition
      reactions of the corannulene oxyradical.

PMID- 28435937
TI  - Expression of Syntaxin 2 in Bovine Sperm.
AB  - Syntaxins are membrane integrated Q-SNARE proteins known to participate in
      exocytosis. Vesicle docking involves the binding of two plasma membrane proteins,
      syntaxin and SNAP-25, to the vesicle membrane protein VAMP to form a stable
      trimeric core complex; synaptophysin is thought to regulate the formation of this
      complex. Although the members of Q-SNARE proteins are characterized in somatic
      cells, it is not known whether related proteins function in the sperm acrosome
      reaction. The objective of the present study is to identify and localize syntaxin
      in bovine epididymal spermatozoa and to determine the fate of syntaxin 2 during
      the acrosome reaction. Western blots of caput and cauda sperm lysates and plasma
      membrane fractions, stained with anti-syntaxin 2, revealed the presence of a
      31kDa band in both sperm lysates and plasma membrane fractions, respectively.
      Indirect immunofluorescence localized syntaxin 2 to the anterior but not the
      equatorial regions of the acrosomal segment. Several biochemical analyses
      demonstrated that syntaxin 2 is an integral component of bovine cauda sperm
      plasma membranes. Our immunoblot data reveals that syntaxin 2 of bovine cauda
      sperm is released after lysophosphatidylcholine (LPC)-induced acrosomal
      exocytosis. It is assumed that syntaxin 2 may be involved in triggering the
      acrosome reaction through a ligand-receptor mediated signal transduction pathway.

PMID- 28435939
TI  - Conjugated D-A porphyrin dimers for solution-processed bulk-heterojunction
      organic solar cells.
AB  - Three conjugated D-A porphyrin dimers (DPP-ZnP-E)2, (DPP-ZnP-E)2-2T and (DPP-ZnP
      E)2-Ph linked with diethynylene, diethynylene-dithiophene and diethynylene
      phenylene have been developed for bulk heterojunction solar cells with high power
      conversion efficiencies of 4.50%, 5.50% and 6.42%, respectively, when blended
      with PC61BM as the electron acceptor material.

PMID- 28435940
TI  - An overview of the performance of the COSMO-RS approach in predicting the
      activity coefficients of molecular solutes in ionic liquids and derived
      properties at infinite dilution.
AB  - This paper reports a comprehensive evaluation of the conductor-like screening
      model for real solvents (COSMO-RS) in predicting infinite dilution activity
      coefficients (gammainfinity) of molecular solutes in ionic liquids (ILs). In
      particular, comparative analysis of two quantum chemical levels of calculations
      used in the COSMO part of COSMO-RS, namely, TZVP-COSMO and TZVPD-FINE, is
      presented and discussed. The final assessment of the model performance is
      established based on a comparison of its predictions with the experimental data
      pool consisting of 41 868 data points extracted form 182 references, covering 233
      ILs (including salts belonging to 12 different cationic families) and 150
      molecular solutes (including a great variety of non-polar, polar and self
      associating organic compounds and water) combined with 8554 distinct binary
      systems. The impact of the chemical family of both IL and molecular solute on the
      accuracy of the COSMO-RS predictions is analyzed in terms of both quantitative
      and qualitative measures. Relevant thermodynamic properties derived from
      gammainfinity, namely, infinite dilution partial excess enthalpy of mixing and
      infinite dilution selectivity are considered and their values obtained from
      experimental and COSMO-RS predicted gammainfinity data are confronted. Finally,
      the impact of the molecular conformation of cations/anions/solutes on the quality
      of predictions is demonstrated based on some representative systems.

PMID- 28435942
TI  - Bipolar resistive switching with negative differential resistance effect in a
      Cu/BaTiO3/Ag device.
AB  - We demonstrate that a bipolar non-volatile resistive switching behaviour with
      negative differential resistance (NDR) effect is realized in a Cu/BaTiO3/Ag
      device, which was deposited on a Si substrate via magnetron sputtering equipment.
      We suggest that the bipolar resistive switching is dominated by the
      trapping/detrapping of electrons at the BaTiO3-Cu interface. In addition, we
      demonstrate that the device exhibits good performance, including a large on/off
      ratio, high reliability and long retention time. Therefore, BaTiO3 may become a
      good candidate for application in resistive switching random access memory (RRAM)
      devices.

PMID- 28435943
TI  - Influence of charged defects on the interfacial bonding strength of tantalum- and
      silver-doped nanograined TiO2.
AB  - A nano-grained layer including line defects was formed on the surface of a Ti
      alloy (Tialloy, Ti-6Al-4V ELI). Then, the micro- and nano-grained Tialloy with
      the formation of TiO2 on its top surface was coated with a bioactive Ta layer
      with or without incorporating an antibacterial agent of Ag that was manufactured
      by magnetron sputtering. Subsequently, the influence of the charged defects (the
      defects that can be electrically charged on the surface) on the interfacial
      bonding strength and hardness of the surface system was studied via an electronic
      model. Thereby, material systems of (i) Ta coated micro-grained titanium alloy
      (Ta/MGTialloy), (ii) Ta coated nano-grained titanium alloy (Ta/NGTialloy), (iii)
      TaAg coated micro-grained titanium alloy (TaAg/MGTialloy) and (iv) TaAg coated
      nano-grained titanium alloy (TaAg/NGTialloy) were formed. X-ray photoelectron
      spectroscopy was used to probe the electronic structure of the micro- and nano
      grained Tialloy, and so-formed heterostructures. The thin film/substrate
      interfaces exhibited different satellite peak intensities. The satellite peak
      intensity may be related to the interfacial bonding strength and hardness of the
      surface system. The interfacial layer of TaAg/NGTialloy exhibited the highest
      satellite intensity and maximum hardness value. The increased bonding strength
      and hardness in the TaAg/NGTialloy arises due to the negative core charge of the
      dislocations and neighbor space charge accumulation, as well as electron
      accumulation in the created semiconductor phases of larger band gap at the
      interfacial layer. These two factors generate interfacial polarization and
      enhance the satellite intensity. Consequently, the interfacial bonding strength
      and hardness of the surface system are improved by the formation of mixed
      covalent-ionic bonding structures around the dislocation core area and the
      interfacial layer. The bonding strength relationship by in situ XPS on the
      metal/TiO2 interfacial layer may be examined with other noble metals and applied
      in diverse fields.

PMID- 28435944
TI  - Surface-controlled preparation of EuWO4(OH) nanobelts and their hybrid with Au
      nanoparticles as a novel enzyme-free sensing platform towards hydrogen peroxide.
AB  - EuWO4(OH) nanobelts were synthesized for the first time via a thiourea-assisted
      hydrothermal reaction. The nanobelts were further hybridized with Au
      nanoparticles (NPs) and showed excellent performance in H2O2 detection, due to
      both the enzyme-mimic catalytic properties of Au NPs and the radical responsive 
      OH groups on the EuWO4(OH) nanobelt surfaces.

PMID- 28435945
TI  - Enhanced durability and activity of the perovskite electrocatalyst Pr0.5Ba0.5CoO3
      delta by Ca doping for the oxygen evolution reaction at room temperature.
AB  - A promising Ca doping approach was reported to improve the durability and
      electrocatalytic OER activity of the perovskite Pr0.5Ba0.5CoO3-delta (PBC).
      Compared to the pristine PBC, the electrocatalytic activity of Ca-doped
      Pr0.5Ba0.3Ca0.2CoO3-delta perovskite was increased by ca. 90%. More importantly,
      its durability was significantly enhanced after doping with calcium.

PMID- 28435946
TI  - Faraday Discussions meeting Catalysis for Fuels.
AB  - Welcome to Africa was the motto when after more than 100 years the flag ship
      conference series of the Royal Society of Chemistry, the Faraday Discussions was
      hosted for the first time on the African Continent. Under the fitting topic
      'Catalysis for Fuels' over 120 delegates followed the invitation by the
      conference chair Prof. Graham Hutchings FRS (Cardiff Catalysis Institute), his
      organizing committee and the co-organizing DST-NRF Centre of Excellence in
      Catalysis c*change (). In the presentations of 21 invited speakers and 59
      posters, cutting edge research in the field of catalysis for fuels, designing new
      catalysts for synthetic fuels, hydrocarbon conversion in the production of
      synthetic fuels and novel photocatalysis was presented over the two-day meeting.
      The scene was set by the opening lecture of Prof. Enrique Iglesias (UC Berkeley)
      and wrapped-up with the concluding remarks by Philip Gibson (SASOL).

PMID- 28435947
TI  - Iridium(iii) catalyzed regioselective amidation of indoles at the C4-position
      using weak coordinating groups.
AB  - The C4-aminated indole scaffold is frequently encountered in several natural
      products and biologically active compounds. Herein we disclose a simple and short
      synthetic route for the amidation of indoles at the C4 position by employing an
      aldehyde as a directing group and Ir(iii) as a catalyst. This strategy offers
      high selectivity for the C4-amidation of unprotected and protected indoles. A
      simple deprotection of the tosyl group leads to the formation of C4-amino indole
      derivatives, which are useful synthons for synthesizing natural products in the
      teleocidin family.

PMID- 28435948
TI  - Diversification reactions of gamma-silyl allenyl esters: selective conversion to
      all-carbon quaternary centers and gamma-allene dicarbinols.
AB  - The unique reactivity of gamma-silyl allenyl esters is described. Taking
      advantage of the silyl group as a fluoride acceptor, these allenoates readily
      underwent addition to a variety of electrophiles to selectively yield products
      with all-carbon quaternary centers or allenoate dicarbinols. These dicarbinols
      were subsequently converted to novel highly substituted 6-hydro-2-pyrones.

PMID- 28435949
TI  - Cooperative carbon monoxide to formyl reduction at a trifunctional PBB frustrated
      Lewis pair.
AB  - Twofold hydroboration of the bulky Mes*P(vinyl)2 phosphane with Piers' borane
      [HB(C6F5)2] followed by C6F5/H exchange with 9-BBN generated a reactive P/B/BH
      FLP structure that cleanly reduced carbon monoxide at the trifunctional
      frustrated Lewis pair framework to the [B]-formyl stage.

PMID- 28435950
TI  - Solvent-free on-surface synthesis of boroxine COF monolayers.
AB  - A protocol is proposed for the solvent-free on-surface synthesis of covalent
      organic framework monolayers by condensation of diboronic acids. Monomers are
      vapor-deposited and water is used for equilibrium regulation. Samples are
      characterized on progressively smaller length scales by light microscopy,
      Scanning Electron Microscopy, and Scanning Tunneling Microscopy.

PMID- 28435951
TI  - A novel method for in situ synthesis of SERS-active gold nanostars on
      polydimethylsiloxane film.
AB  - A novel one-step in situ synthesis of gold nanostars (AuNSs) on a pre-cured
      polydimethylsiloxane (PDMS) film is proposed for the fabrication of highly
      sensitive surface-enhanced Raman scattering (SERS) substrates. Plasmonic activity
      of the substrates was investigated by collecting SERS maps of 4-mercaptobenzoic
      acid (4-MBA). The applicability of these flexible substrates is further
      demonstrated by SERS-based pesticide detection on fruit skin.

PMID- 28435952
TI  - Foscarnet calcium microcrystals as the intravitreal drug depot.
AB  - Foscarnet sodium is an antiviral drug for the treatment of CMV retinitis,
      currently in the form of twice-weekly intravitreal injection. Here we developed
      foscarnet calcium microcrystals as the drug depot, and using the rabbit model we
      demonstrated that the injected microcrystals maintained a therapeutically
      relevant drug concentration in the vitreous for more than 3 months.

PMID- 28435953
TI  - Mercurophilic interactions: a theoretical study on the importance of ligands.
AB  - In this work, a theoretical analysis of intermolecular HgHg contacts in the
      presence of different ligands is presented. A survey of structural databases to
      explore the geometrical preferences among experimental structures presenting
      short Hg(ii)Hg(ii) contacts reveals the main interaction topologies depending on
      the nature of the ligand. A benchmark study of several dispersion corrected
      density functional methods is carried out to determine the optimal computational
      methodology for the theoretical study of such interaction. This methodology is
      later used in the study of several dimers of dicoordinated mercury compounds
      [HgX2]2 (X = Cl, Br, I, CN, CH3, CF3, SiH3, SiMe3) as well as to evaluate the
      stability of different interacting topologies in such dimers. It is found that,
      whenever possible, two mercury-containing molecules will preferentially join
      through intermolecular HgX donor-acceptor interactions and only ligands devoid of
      atoms with lone pairs available for such interactions can form dimers attached
      predominantly via mercurophilic interactions.

PMID- 28435954
TI  - Electrostatically stabilized hybrids of carbon and maghemite nanoparticles:
      electrochemical study and application.
AB  - Binary hybrids have been investigated for the past few decades due to the
      emerging properties of nanoparticle composites. Electrostatically stabilized core
      shell nanostructures composed of surface active magnetic nanoparticles (SAMNs)
      and differently charged carbon nanomaterials display specific electrochemical
      properties. In this work, a set of binary hybrids that include a new class of
      magnetic nanoparticles is presented and the electrochemical features of the
      hybrids are reported. Gallic acid derived carbon dots (GA-CDs), PEG derived
      graphene dots (PEG-GDs), and quaternized carbon dots (Q-CDs) characterized by
      different charged groups were used for the preparation of different complexes
      with SAMNs. Thus, a set of six binary nanomaterials was obtained, and
      characterized by electrochemical impedance spectroscopy, cyclic voltammetry and
      chronoamperometry, demonstrating significant differences in the charge transfer
      resistance, capacitive current, electrochemical performance, and reversibility
      with respect to the isolated subunits. Among them, the combination of Q-CDs with
      an excess of SAMNs led to a Q-CD@SAMN hybrid, which displayed peculiar
      electrocatalytic properties attributable to the influence of the strong
      electrostatic interactions exerted by Q-CDs on the SAMN surface. Notwithstanding
      their small fraction (around 1% w/w), Q-CDs oriented the electrocatalysis of
      SAMNs toward the selective electro-oxidation of polyphenols at low applied
      potentials (+0.1 V vs. SCE). Finally, the Q-CD@SAMN hybrid was used for the
      development of a coulometric sensor for polyphenols, composed of a simple carbon
      paste electrode in a small volume electrochemical flow cell (1 MUL), and used for
      the complete direct electro-oxidation of polyphenols from plant extracts.

PMID- 28435955
TI  - High-resolution FTIR spectroscopy of trisulfane HSSSH: a candidate for detecting
      parity violation in chiral molecules.
AB  - We report the first successful high-resolution analyses of the Fourier transform
      infrared (FTIR) spectrum of trisulfane. A band centered at 861.0292 cm-1 can be
      assigned unambiguously to the chiral trans conformer by means of ground state
      combination differences in comparison with known rotational spectra. A second
      band near 864.698 cm-1 is tentatively assigned to the cis conformer by comparison
      with theory. The results are discussed in relation to their importance for
      experimental attempts to measure the parity violating energy difference DeltapvE
      between the ground states of enantiomers of chiral molecules.

PMID- 28435956
TI  - Unusual emission properties of the selected organosilicon compounds containing a
      styryl-carbazole chromophore: inversion of the singlet excited states.
AB  - The spectroscopic and photophysical properties of silicon-containing styryl
      carbazole were investigated in various solvents, and the results were analyzed
      with reference to its carbon derivatives. In n-hexane, both the silicon- and the
      carbon-containing compounds had very similar emission properties. In
      acetonitrile, the emission properties remained the same for the C-compound but
      changed significantly for the Si-compounds. In particular, the fluorescence
      spectra of the latter were red-shifted, and their radiative rate constants were
      even 7 times larger than in n-hexane, which suggested that the emissive states of
      the silicon-containing compounds were different in these two solvents. DFT
      calculations using the CAM-B3LYP functional showed that the emissive state of the
      C-compound involves the LUMO+1 orbital regardless of the medium. In contrast, for
      the Si-compound, changing the medium from n-hexane to acetonitrile resulted in
      the inversion of the emissive states from an excited state involving the LUMO+1
      orbital (the dipole moment MU = 4.2 D) to an excited state involving the LUMO
      orbital (MU = 8.9 D).

PMID- 28435957
TI  - An asymmetric vinylogous Mukaiyama-Michael reaction of alpha,beta-unsaturated 2
      acyl imidazoles catalyzed by chiral Sc(iii)- or Er(iii)-pybox complexes.
AB  - A highly diastereo- and enantioselective vinylogous Mukaiyama-Michael reaction of
      silyloxyfurans with alpha,beta-unsaturated 2-acyl imidazoles catalyzed by either
      chiral Sc(iii) or Er(iii) complexes of a pybox ligand has been reported. The
      enantioenriched gamma-butenolides formed in the reaction were further transformed
      into highly functionalized gamma-lactones found as important structural
      frameworks in a wide range of biologically active natural products.

PMID- 28435958
TI  - Potential energy surface for the reaction Sm+ + CO2 -> SmO+ + CO: guided ion beam
      and theoretical studies.
AB  - The potential energy surface (PES) for the oxidation of samarium cations by
      carbon dioxide is explored both experimentally and theoretically. Using guided
      ion beam tandem mass spectrometry, several reactions are examined as a function
      of kinetic energy. These include the title reaction as well as its reverse along
      with the collision-induced dissociation of Sm+(CO2) and OSm+(CO) with Xe.
      Analysis of the kinetic energy dependent cross sections yields barriers for the
      forward and reverse oxidation reaction of 1.77 +/- 0.11 and 2.04 +/- 0.13 eV,
      respectively, and Sm+-OCO and OSm+-CO bond dissociation energies (BDEs) of 0.42
      +/- 0.03 and 0.97 +/- 0.07 eV, respectively. BDEs for Sm+(CO2)x for x = 2 and 3
      are also determined as 0.40 +/- 0.13 and 0.48 +/- 0.12 eV, respectively. The PESs
      for the title reaction along the sextet and octet spin surfaces are also examined
      theoretically at the MP2 and CCSD(T) levels using both effective core potential
      and all-electron basis sets. Reasonable agreement between theory and experiment
      is obtained for the experimentally characterized intermediates, although all
      electron basis sets and spin-orbit effects are needed for quantitative agreement.
      The observed barrier for oxidation is shown to likely correspond to the energy of
      the crossing between surfaces corresponding to the ground state electronic
      configuration of Sm+ (8F,4f66s1) and an excited surface having two electrons in
      the valence space (excluding 4f), which are needed to form the strong SmO+ bond.

PMID- 28435959
TI  - Luminescence-colour-changing sensing of Mn2+ and Ag+ ions based on a white-light
      emitting lanthanide coordination polymer.
AB  - The white-light emission of a triple-component lanthanide coordination polymer
      turns to blue and red upon adding Mn2+ and Ag+ ions, respectively.

PMID- 28435960
TI  - Meteorite impacts on ancient oceans opened up multiple NH3 production pathways.
AB  - A recent series of shock experiments by Nakazawa et al. starting in 2005 (e.g.
      [Nakazawa et al., Earth Planet. Sci. Lett., 2005, 235, 356]) suggested that
      meteorite impacts on ancient oceans would have yielded a considerable amount of
      NH3 to the early Earth from atmospheric N2 and oceanic H2O through reduction by
      meteoritic iron. To clarify the mechanisms, we imitated the impact events by
      performing multi-scale shock technique-based ab initio molecular dynamics in the
      framework of density functional theory in combination with multi-scale shock
      technique (MSST) simulations. Our previous simulations with impact energies close
      to that of the experiments revealed picosecond-order rapid NH3 production during
      shock compression [Shimamura et al., Sci. Rep., 2016, 6, 38952]. It was also
      shown that the reduction of N2 took place with an associative mechanism as seen
      in the catalysis of nitrogenase enzymes. In this study, we performed an MSST-AIMD
      simulation to investigate the production by meteorite impacts with higher
      energies, which are closer to the expected values on the early Earth. It was
      found that the amount of NH3 produced further increased. We also found that the
      increased NH3 production is due to the emergence of multiple reaction mechanisms
      at increased impact energies. We elucidated that the reduction of N2 was not only
      attributed to the associative mechanism but also to a dissociative mechanism as
      seen in the Haber-Bosch process and to a mechanism through a hydrazinium ion. The
      emergence of these multiple production mechanisms capable of providing a large
      amount of NH3 would support the suggestions from recent experiments much more
      strongly than was previously believed, i.e., shock-induced NH3 production played
      a key role in the origin of life on Earth.

PMID- 28435961
TI  - Single-photon Coulomb explosion of methanol using broad bandwidth ultrafast EUV
      pulses.
AB  - Single-photon Coulomb explosion of methanol is instigated using the broad
      bandwidth pulse achieved through high-order harmonics generation. Using 3D
      coincidence fragment imaging of one molecule at a time, the kinetic energy
      release (KER) and angular distributions of the products are measured in different
      Coulomb explosion (CE) channels. Two-body CE channels breaking either the C-O or
      the C-H bonds are described as well as a proton migration channel forming H2O+,
      which is shown to exhibit higher KER. The results are compared to intense-field
      Coulomb explosion measurements in the literature. The interpretation of broad
      bandwidth single-photon CE data is discussed and supported by ab initio
      calculations of the predominant C-O bond breaking CE channel. We discuss the
      importance of these findings for achieving time resolved imaging of ultrafast
      dynamics.

PMID- 28435962
TI  - Dissociation of cyclopropane in double ionization continuum.
AB  - Dissociative double photoionization of cyclopropane is studied in the inner
      valence region using tunable synchrotron radiation. With the aid of ab initio
      quantum chemical calculations the energies of dication states and their favoured
      fragmentation pathways are determined. These are compared to the experimental
      appearance energies of two-body fragmentation processes and to the kinetic energy
      released upon dissociation. Photon energy dependent state-selective dissociation
      in the 25-35 eV range is found. Calculations of dissociation pathways suggest
      that cyclopropane ring-deformation is selectively triggered at certain photon
      energies. The calculations suggest that initial ring deformation essentially
      determines the population of different dication states that function as gateways
      for particular dissociation channels. The measurements show that stepwise
      ionization processes populate dissociative 3e'-2 states via ring-opening and Jahn
      Teller active states at photon energies below the double-ionization threshold.
      For energies above the double-ionization threshold the kinematics indicate that
      double ionization takes place predominantly within the Franck-Condon region
      populating 3e'-1 1e''-1 states.

PMID- 28435963
TI  - Thermodynamic and morphological characterization of Turing patterns in non
      isothermal reaction-diffusion systems.
AB  - The effect of temperature on the bifurcation diagram and Turing instability
      domain under non isothermal conditions is studied in the reversible Gray-Scott
      model. After adding the energy balance to the cubic autocatalytic model, the
      thermostat temperature and heat transfer coefficient are used as control
      parameters in the Turing pattern formation. The patterns obtained in the domain
      of the thermal parameter are characterized by quantifying the overall entropy
      generation rate and two topological indices; Shannon entropy and Minkowski
      functionals. The results show that it is possible to induce transitions between
      Turing patterns of different morphologies by regulating the temperature, and that
      these transitions take place at a lower entropy generation value compared to
      other parameters, such as kinetic constants and reactant fluxes. Finally, a
      correlation between entropy generation and topological indices shows that a
      difference between direct and inverse patterns is mainly morphological and not
      energetic.

PMID- 28435964
TI  - Kinetics of CO2 diffusion in human carbonic anhydrase: a study using molecular
      dynamics simulations and the Markov-state model.
AB  - Molecular dynamics (MD) simulations, in combination with the Markov-state model
      (MSM), were applied to probe CO2 diffusion from an aqueous solution into the
      active site of human carbonic anhydrase II (hCA-II), an enzyme useful for
      enhanced CO2 capture and utilization. The diffusion process in the hydrophobic
      pocket of hCA-II was illustrated in terms of a two-dimensional free-energy
      landscape. We found that CO2 diffusion in hCA-II is a rate-limiting step in the
      CO2 diffusion-binding-reaction process. The equilibrium distribution of CO2 shows
      its preferential accumulation within a hydrophobic domain in the protein core
      region. An analysis of the committors and reactive fluxes indicates that the main
      pathway for CO2 diffusion into the active site of hCA-II is through a binding
      pocket where residue Gln136 contributes to the maximal flux. The simulation
      results offer a new perspective on the CO2 hydration kinetics and useful insights
      toward the development of novel biochemical processes for more efficient CO2
      sequestration and utilization.

PMID- 28435965
TI  - Conformational and hydration properties modulate ice recognition by type I
      antifreeze protein and its mutants.
AB  - The mechanism of ice recognition by antifreeze protein (AFP) is a topic of recent
      interest. Here, using equilibrium simulations and free energy calculations, we
      provide structural rationale to the observed experimental anomalies on type I AFP
      (wfAFP isoform HPLC6) and its mutants as well as probe the molecular origin of
      ice recognition by them. Our results clearly demonstrate that the interplay
      between the conformational and hydration properties dictates the ice binding
      ability of type I AFP and its mutants. We find that HPLC6 exists as a highly
      stable long helix which adsorbs on the ice surface through the ordered water
      cages around the CH3 group of threonine (THR) residues, rather than directly
      binding to the ice surface via threonine (THR) through hydrogen bonding. Upon
      mutating THR with serine (SER), the straight helix conformation of HPLC6
      disappears and the most stable conformation is a kinked helix devoid of ice
      binding ability. Free energy calculations reveal that there is a dynamic
      equilibrium between straight and bent helical conformations in the case of a
      valine (VAL) mutant. The straight long helical form of the VAL mutant also has
      the ability to form an ordered water cage structure around the CH3 groups of the
      VAL residues and thereby efficiently adsorbs on an ice plane similar to the wild
      type AFP.

PMID- 28435966
TI  - Water structuring above solutes with planar hydrophobic surfaces.
AB  - Many important biological solutes possess not only polar and hydrogen bonding
      functionalities, but also weakly-hydrating, or hydrophobic, surfaces. Theories of
      the hydration of such surfaces predict that their solvent interactions will
      change from a wetting type interaction to a dewetting regime as a function of the
      solute size, with a gradual transition in behavior taking place around
      characteristic lengths of ~1 nm. Aggregations of non-polar species over this size
      range will undergo a transition from being dominated by entropy to being
      dominated by enthalpy. These transitions can be understood in part in terms of
      the geometries required of the solvating water molecules. We report here a series
      of simulations in aqueous solution of organic molecules with planar faces of
      increasing size, ranging from cyclopropane to circumcircumcoronene, in order to
      explore the transition in behavior for such solutes as their size increases. For
      this series, the dewetting transition occurred gradually, converging
      asymptotically to a limiting separation value for first layer water molecules of
      around 3.3 A, while the transition in hydrogen bonding orientational structure
      occurred between cyclopropane and cyclopentadene. Water immediately adjacent to
      the largest planar hydrophobic surfaces oriented in ways that resembled on
      average the structural organization of the basal planes of ice.

PMID- 28435967
TI  - Thermal mismatch strain induced disorder of Y2Mo3O12 and its effect on thermal
      expansion of Y2Mo3O12/Al composites.
AB  - Fully dense Y2Mo3O12/Al composites were prepared by squeeze-casting. Relatively
      mild conditions of 750  degrees C/20 min/50 MPa were used in order to avoid
      reaction of the components. SEM, Raman spectroscopy, XRD and dilatometry were
      used to characterize the microstructures and morphologies of the composites. Zero
      thermal expansion was achieved in the temperature range where the thermal
      mismatch strain was zero. We show that the CTE mismatch of Al and Y2Mo3O12
      results in compressive and tensile strains that distort the Y2Mo3O12 lattice. We
      establish a novel method to measure the negative thermal expansion (NTE)
      materials' CTE under strain by measuring the composites' CTE and calculating the
      thermal mismatch strain between the NTE ceramic and the metal matrix. The
      relationship between thermal strain and Raman shift is established and measured
      and the simulated results are in good agreement. We also find Y2Mo3O12 to have a
      positive CTE when the surface strain is >=0.80 * 10-2%.

PMID- 28435968
TI  - Unexpected proton mobility in the bulk phase of cholinium-based ionic liquids:
      new insights from theoretical calculations.
AB  - We have explored by means of ab initio molecular dynamics two ionic liquids based
      on the combination of a choline cation with deprotonated cysteine and aspartic
      acid anions. While the combination of the strong base choline with various other
      amino-acids leads to the formation of a highly ionized medium where proton
      transfer is negligible, the presence of additional protic functions on the SH and
      COOH groups leads to an unexpected and interesting behavior and to a sizable
      migration of their acidic protons onto the NH2 basic terminals. As far as we know
      this is the first time that such proton migration, which in water leads to the
      well-known zwitterionic form of aminoacids, is observed to take place in their
      ionized, anionic form. We analyze in detail such dynamical effects using accurate
      ab initio molecular dynamics computations validated through comparison with X-ray
      scattering data.

PMID- 28435969
TI  - Solution-processed multilayer green electrophosphorescent devices with self-host
      iridium dendrimers as the nondoped emitting layer: achieving high efficiency
      while avoiding redissolution-induced batch-to-batch variation.
AB  - Self-host Ir dendrimers have been adopted as the nondoped emitting layer for the
      successful construction of multilayer green phosphorescent organic light-emitting
      diodes (PhOLEDs) prepared via layer-by-layer solution processing with orthogonal
      solvents. Unlike previous doped systems, the risk of small-molecular-phosphor
      redissolution by alcohols and the resultant serious batch-to-batch variation can
      be eliminated. Consequently, a record-high external quantum efficiency of 21.2%
      together with good reproducibility is achieved for the green-emitting Ir
      dendrimer G2, which displays sufficient alcohol resistance owing to the effective
      encapsulation from the second generation dendritic wedge. The obtained
      performance is highly competitive with those of doped devices, while avoiding the
      unwanted redissolution-induced batch-to-batch variation simultaneously,
      representing an important development in the solution fabrication of multilayer
      PhOLEDs based on a nondoped system.

PMID- 28435970
TI  - [AMP-activated kinase activation inhibits transforming growth factor-beta1
      production in cardiac fibroblasts via targeting C/EBPbeta].
AB  - AMP-activated protein kinase (AMPK) activation has been shown to protect against
      fibrosis. However, the underlying mechanism remains unclear. Here we explored the
      effect of AMPK activation on transforming growth factor-beta1 (TGFbeta1)
      production induced by angiotensin II (AngII) in cardiac fibroblasts and the
      underlying mechanisms. Adult mouse cardiac fibroblasts were isolated. TGFbeta1
      and AMPK activity were determined by ELISA and Western blots, respectively.
      Pretreatment of AMPK activator AICAR inhibited TGFbeta1 production induced by
      AngII in cardiac fibroblasts, which was reversed by AMPK inhibitor compound C.
      Furthermore, bioinformatics predicted a potential CCAAT/enhancer-binding protein
      beta (C/EBPbeta) binding site in the promoter region of the mouse Tgfb1 gene.
      Luciferase reporter with wild type, but not deleted, C/EBPbeta binding sites
      transfection in mouse embryonic fibroblasts showed increased TGFbeta1
      transcriptional activity induced by AngII, indicating that C/EBPbeta mediates
      AngII-induced TGFbeta1 transcript expression. Pretreatment of AICAR inhibited
      C/EBPbeta expression induced by AngII. In conclusion, AMPK activation inhibited
      TGFbeta1 production induced by AngII in cardiac fibroblasts through targeting
      C/EBPbeta. This finding provides a new mechanism underlying the anti-fibrogenic
      effects of AMPK activation.

PMID- 28435971
TI  - [Mechanisms underlying rat coronary arterial vasoconstriction induced by blockade
      of inward rectifier potassium channels with BaCl2].
AB  - In order to explore the mechanisms underlying the vasoconstriction induced by
      blockade of inward rectifier K+ channels (Kir) with BaCl2, myogenic tone of
      isolated rat coronary artery (RCA) was recorded with wire myograph. The
      dependence of BaCl2- induced contraction on intracellular Ca2+ ([Ca2+]i) release
      and extracellular Ca2+ ([Ca2+]o) influx was studied by Ca2+ deprivation and
      restoration. The mechanisms underlying BaCl2-induced RCA contraction were
      investigated with specific inhibitors. BaCl2 (0.1-1.0 mmol/L) contracted isolated
      RCA in a concentration-dependent manner and the maximal contraction was (5.69 +/-
      1.07) mN, nearly equal to contraction induced by 60 mmol/L KCl. The contractions
      induced by BaCl2 in Ca2+-free solution and by followed restoration of 2.5 mmol/L
      Ca2+ accounted for (35.44 +/- 6.72)% and (64.56 +/- 5.94)%, respectively. Calcium
      channel blocker nifedipine (0.3 MUmol/L), cyclooxygenase inhibitor indomethacin
      (100 MUmol/L), ERK1/2 inhibitor PD98059 (10 MUmol/L) and chloride channel blocker
      niflumic acid (100 MUmol/L) pretreatment depressed the BaCl2-induced maximal
      contraction by (87.82 +/- 5.43)% (P < 0.01), (73.23 +/- 5.47)% (P < 0.01), (75.69
      +/- 7.94)% (P < 0.01) and (83.24 +/- 7.69)% (P < 0.01), respectively. These
      results demonstrate that BaCl2 induces vasoconstriction in RCA by enhancing both
      [Ca2+]i release and [Ca2+]o influx, and suggest that increase of prostanoids
      synthesis, activation of calcium channels and chloride channels, as well as
      ERK1/2 pathway may be involved in this process.

PMID- 28435972
TI  - [GLP-1/GIP/Gcg receptor Triagonist improves the cognitive behaviors in triple
      transgenic mice of Alzheimer's disease].
AB  - Alzheimer's disease (AD) is a progressively neurodegenerative disorder, which
      seriously affects human health but is still irreversible up to now. Recent
      studies indicate that type 2 diabetes mellitus (T2DM) is an important risk factor
      for AD, and the drugs used for treatment of T2DM have shown some neuroprotective
      effects in the treatment of AD. Glucagon-like peptide-1 (GLP-1)/ glucose
      dependent insulinotropic polypeptide (GIP)/glucagon (Gcg) receptor Triagonist is
      a new monomeric polypeptide equally activating the GLP-1/GIP/Gcg receptors, which
      is built on the basis of GLP-1/Gcg receptor coagonist core sequence, and
      incorporated with partial amino acids of GIP. Recently, the Triagonist has been
      reported to be effective in alleviating diabetic complications in rodent models
      of obesity. The present study observed for the first time the cognitive
      improvement effects of the Triagonist in the triple-transgenic AD mice (3xTg-AD)
      by using multiple behavioral techniques, and explored its probable molecular
      mechanisms using ELISA and Western blot. The results showed that the chronic
      treatment with the Triagonist (i.p.) significantly reversed the impairments in
      working memory of 3xTg-AD mice, with an obvious increase in the percentage of
      correct spontaneous alternation in the Y maze; the Triagonist treatment also
      improved long-term spatial memory and re-learning ability of 3xTg-AD mice in
      classical Morris water maze and reverse water maze tests, with decreased escape
      latency in under water platform tests and increased swimming time in probe tests.
      ELISA and Western blot experiments showed that the Triagonist up-regulated the
      levels of cAMP, PKA and p-CREB in the hippocampus of 3xTg-AD mice. These results
      indicate that GLP-1/GIP/Gcg receptor Triagonist can improve the cognitive
      behaviors in 3xTg-AD mice, and the up-regulation of hippocampal cAMP/PKA/CREB
      signal pathway may mediate the neuroprotection of the Triagonist, suggesting that
      the GLP-1/GIP/Gcg receptor Triagonist may be a novel therapeutic strategy for the
      treatment of AD.

PMID- 28435973
TI  - Acclimatization to middle altitude hypoxia protects against developmental and
      cognitive deficits caused by acute fetal hypoxia in mice.
AB  - Acute fetal hypoxia (AFH) can elicit postnatal motor deficits and cognitive
      impairments. To test whether lifelong acclimatization to middle altitude (MA)
      hypoxia has protective effects on the impairments caused by AFH, ICR mice bred at
      1 900 m altitude for 6-7 generations were evaluated under AFH. On gestation day 9
      (GD 9), 13 (GD 13) or 17 (GD 17), pregnant mice received a single exposure to
      acute hypoxia (7% O2, 6 h). Physiological and neurodevelopmental behaviors, motor
      function (open field), spatial learning and memory (Morris water maze), and
      anxiety level (elevated plus maze) were examined in the offspring from neonate to
      adulthood. In the neonatal age, among all the physiological and behavioral
      landmarks, almost no differences were found in the hypoxia groups. In the
      juvenile period, no obvious impairments of motor function and anxiety level were
      found in the hypoxia groups. In the adult period, no obvious impairment of motor
      function was found in hypoxia groups; Interestingly, AFH groups' offspring showed
      normal or enhanced long-term spatial memory ability after AFH. These data suggest
      that AFH cause little abnormalities in the offspring of MA-adapted mice. To
      further investigate the underlying mechanisms, the neuronal numbers in behavior
      related brain areas (accumbens nucleus, basal amygdala and hippocampus) were
      counted, and the physiological parameters of the blood were measured. The
      morphological data showed that no obvious neuronal necrosis was found in all
      hypoxia groups. In addition, blood tests showed that red blood corpuscle count,
      hemoglobin concentration and hematocrit levels in mice raised at MA were markedly
      higher in both males and females, compared with controls raised at the sea level.
      These data suggest that lifelong acclimatization to MA hypoxia has protective
      effects against development delay, motor deficits and spatial learning and memory
      impairments induced by AFH, and the protective effects may be due to higher
      hemoglobin concentration and hematocrit levels in the blood. The findings may
      provide a better understanding of fetal hypoxia and potential intervention
      treatments.

PMID- 28435974
TI  - [Antidepressant effects of the extract of Dendrobium nobile Lindl on chronic
      unpredictable mild stress-induced depressive mice].
AB  - To investigate whether the extract of Dendrobium nobile Lindl (DNL) has an
      antidepressant effect on chronic unpredictable mild stress (CUMS)-induced
      depressive mice, 72 BALB/c male mice were randomly divided into the control
      group, the CUMS model group, the extract of DNL groups (50, 100 and 200 mg/kg
      DNL, i.g.) and the paroxetine group (10 mg/kg, i.g.). The different doses of DNL
      or the paroxetine was administered orally once daily to CUMS mice for 8 weeks
      (containing two-week preventive medication before the modeling). The same volume
      of distilled water was given to the control group and the CUMS group. Except for
      the control group, the other mice were exposed to chronic stress for 35 days.
      Behavioral tests were performed by using the sucrose preference test (SPT), the
      novelty-suppressed feeding (NSF) test, the tail suspension test (TST), and the
      forced swim test (FST). The levels of dopamine (DA) and 5-hydroxytryptamine (5
      HT) were measured by the liquid chromatography-mass spectrometer (LC-MS)/MS.
      Compared with the control group, obvious behavioral changes were observed in the
      CUMS group after 5-week CUMS, including a decrease in the sucrose consumption, an
      increase in the latency to feeding in the NSF test and a prolongation of the
      immobility time in the TST. Compared with the CUMS group, the application of DNL
      resulted in a dose-dependent increase in sucrose consumption (P < 0.01) as
      paroxetine (10 mg/kg) did and a significant dose-dependent decrease in the
      latency to feeding in the NSF test (P < 0.05). In the TST, the application of
      paroxetine (10 mg/kg) and the high-dose DNL (200 mg/kg) obviously decreased the
      immobility time when compared with the CUMS group (P < 0.05). In the FST,
      compared with the CUMS group, all the groups had no significant differences in
      the immobility time (P > 0.05). In addition, in the hippocampus and cortex, the
      levels of 5-HT and DA were significantly decreased in the CUMS group compared
      with the control group (P < 0.05). In comparison with the CUMS group, paroxetine
      obviously increased the DA levels in the hippocampus and the cortex and the 5-HT
      level in the hippocampus (P < 0.05). DNL (50 and 200 mg/kg) significantly
      increased the DA level in cerebral cortex of the brain, and DNL (100 and 200
      mg/kg) increased the DA level in the hippocampus. The 5-HT level in the 200 mg/kg
      DNL group was notably increased in both two brain regions (P < 0.05), but the 5
      HT level in the 100 mg/kg DNL group was significantly increased only in the
      hippocampus (P < 0.01). These findings indicate that the extract of DNL has an
      antidepressant-like effect on CUMS-induced depressive mice and its mechanism may
      be related to the changes in DA and 5-HT in the hippocampus and cortex.

PMID- 28435975
TI  - [Effect of bilateral injection of calcitonin gene-related peptide into amygdala
      on learning and memory of mice].
AB  - The aim of the present study was to explore the effects of different doses of
      calcitonin gene-related peptide (CGRP) injected into the central nucleus of
      amygdala on cognitive function, learning and memory of mice. C57BL/6J mice (30
      days old) were randomly divided into control, sham, and three CGRP groups (10
      mice for each group). Three doses of CGRP (200, 400 and 800 ng) were bilaterally
      administered into the central nucleus of the amygdala. Open field test was used
      to assess cognitive function. Novel object recognition and Morris water maze test
      were used to evaluate learning and memory of the mice. The results of open field
      test showed that 800 ng CGRP significantly increased the locomotive score. The
      results of novel objective recognition test showed that 400 ng CGRP significantly
      increased the recognition index. Compared with control group, 400 and 800 ng CGRP
      groups showed significantly shortened latency period and increased crossing
      times. Simultaneously, the latency periods of 400 and 800 ng CGRP groups were
      shorter than that of 200 ng CGRP group. These results suggest that bilateral
      injection of CGRP into amygdala dose-dependently enhances the learning and memory
      function of mice.

PMID- 28435976
TI  - [Role of IgG plasma cells in the change of protein C system in ulcerative
      colitis].
AB  - The present study is designed to explore the role of plasma cells in the change
      of protein C system (PCS) in ulcerative colitis (UC). Dextran sulfate sodium
      (DSS, 4% in concentration) was used to induce mouse UC model. The plasma cells
      and the type of immune complex in colon were observed by immunofluorescence. The
      amount and type of plasma cells separated from colonic mucosal lamina propria
      were detected by flow cytometry using anti-CD54+CD38+ and IgA/M/G antibodies,
      respectively. After stimulation of macrophages by IgG type immune complex, TNF
      alpha and IL-6 levels were evaluated by ELISA. After co-incubation of
      microvascular endothelial cells with TNF-alpha or IL-6, the expressions of
      endothelial protein C receptor (EPCR) and thrombomodulin (TM), and the activity
      of activated protein C (APC) were examined. As the results showed, the IgG type
      plasma cells infiltration and the quantity of IgG type immune complex were
      increased in DSS group in comparison with control group. After incubation with
      IgG type immune complex, the levels of TNF-alpha and IL-6 in the supernatant of
      macrophages were increased (P < 0.01) in a concentration-dependent manner.
      Meanwhile, after incubation with TNF-alpha or IL-6, the expressions of EPCR and
      TM in the microvascular endothelial cells were decreased (P < 0.05 or P < 0.01),
      while the activity of APC was reduced (P < 0.05 or P < 0.01). These results
      suggested that the quantity of IgG type plasma cells increases in UC and forms
      immune complexes, which affect the secretion of cytokines from macrophage,
      thereby affecting the function of endothelial cells and finally inhibiting PCS in
      UC. Therefore, plasma cell may be a novel target for the treatment of UC.

PMID- 28435977
TI  - [Inhibitory effects of capsaicin on migration and invasion of breast cancer MDA
      MB-231 cells and its mechanism].
AB  - The aim of this study was to investigate the effects of capsaicin on migration
      and invasion of breast cancer MDA-MB-231 cells and its possible mechanism. The
      MDA-MB-231 cells were incubated in the medium containing different concentrations
      of capsaicin for 24 h. CCK-8 assay was employed to detect the cell viability. The
      cell migration and invasion were assessed by wound healing assay and transwell
      invasion assay, respectively. The protein levels of c-Src, p-c-Src (Tyr416), FAK,
      p-FAK (Tyr576), Paxillin, p-Paxillin (Tyr118), matrix metalloproteinase 2 (MMP2)
      and MMP9 in the MDA-MB-231 cells were detected by Western blotting. The mRNA
      expressions of MMP2 and MMP9 were measured by RT-PCR. The result showed that
      capsaicin (25 and 50 MUmol/L) remarkably reduced the abilities of migration and
      invasion (P < 0.05), inhibited the phosphorylation of c-Src, FAK and Paxillin (P
      < 0.05), and down-regulated MMP2 and MMP9 expressions at mRNA and protein levels
      (P < 0.05) in MDA-MB-231 cells. These effects of capsaicin were all in dose
      dependent manners. These results suggest that capsaicin may suppress the
      migration and invasion of breast cancer MDA-MB-231 cells by inhibiting the
      phosphorylations of c-Src, FAK and Paxillin, and down-regulating the mRNA and
      protein levels of MMP2 and MMP9.

PMID- 28435978
TI  - [Digoxin inhibits migration and invasion of human gastric carcinoma MKN45 cells
      through down-regulation of AEG-1].
AB  - This study was designed to investigate the effect of digoxin on migration and
      invasion of human gastric carcinoma MKN45 cells and its possible mechanism. MKN45
      cells were treated with different concentrations of digoxin for 24 h. The shRNA
      AEG-1 plasmid was transfected into MKN45 cells via lipofectamine to block the
      expression of astrocyte elevated gene-1 (AEG-1). Western blot was used to analyze
      the protein levels of matrix metalloproteinase-9 (MMP-9), E-cadherin and AEG-1.
      The result showed that digoxin reduced the abilities of migration and invasion (P
      < 0.05), up-regulated the protein level of E-cadherin (P < 0.05), and down
      regulated the protein levels of MMP-9 and AEG-1 (P < 0.05) in MKN45 cells in a
      dose-dependent manner. Compared with shControl group, shAGE-1 group showed
      inhibited cellular migration and invasion, higher expression level of E-cadherin,
      and lower expression levels of MMP-9 and AEG-1. These results suggest that
      digoxin suppresses the migration and invasion of human gastric carcinoma MKN45
      cells in a dose-dependent manner through inhibiting the expression of AEG-1, and
      then resulting in the up-regulation of the protein expression of E-cadherin and
      the down-regulation of the protein expression of MMP-9.

PMID- 28435979
TI  - Oxytocin system in neuropsychiatric disorders: Old concept, new insights.
AB  - Oxytocin (OXT) is a neuropeptide that plays a pivotal role among species
      peripherally and centrally. It recently has attracted much attention for its
      involvement in anxiety-related behavior, stress regulation, social behavior and
      various neuropsychiatric disorders. OXT is one of the important mediators of
      emotional and social behaviors such as maternal behavior, fear extinction, social
      support, happiness, and trust. It is also involved in learning and memory
      process. The recent progresses in OXT system have put this neuropeptide as an
      important psychotherapeutic intervention for various psychiatric disorders such
      as stress, anxiety disorders, social phobia, postpartum depression, bipolar
      disorder, autism, and schizophrenia. In this review, we highlight OXT's
      contributions to various physiological functions and psychological disorders and
      discuss its potential use as a therapeutic agent.

PMID- 28435980
TI  - [Glial cells function as neural stem cells and progenitor cells].
AB  - Glial cells, including astrocytes, oligodendrocyte progenitor cells (OPCs), NG2
      glia, etc, are broadly distributed throughout the central nervous system (CNS).
      Also, it has been well known that glial cells play multi-roles in physiological
      and pathological processes in the CNS, such as maintaining homeostasis, providing
      neurotrophins for neurons and regulating neural signal transmission. Recently,
      increasing evidence showed that glial cells may also function as neural
      stem/progenitor cells and contribute to adult neurogenesis or neuroregeneration.
      In pathological conditions, for instance, astrocytes and OPCs could be activated
      to proliferate and differentiate. When cultured in vitro, they could form
      neurospheres which possess the ability to differentiate into astrocytes,
      oligodendrocytes and neurons. Additionally, forced expression of exogenous genes
      in astrocytes and NG2-glia can successfully reprogram them into neurons, which
      may also be suggestive of their stem/progenitor cell features. Here, we review
      current knowledge of the stem cell-like properties of glial cells, including what
      types of glial cells can function as stem/progenitor cells, how they can acquire
      the stem/progenitor potential and what progenies can be produced. These insights
      may foster a better understanding of glial cell biology and function in
      physiological or pathological processes in the CNS and lead to the idea of using
      the stem/progenitor-like glial cells as endogenous cell source for neural repair.

PMID- 28435981
TI  - [Iron metabolism and neonatal hypoxic ischemic brain damage].
AB  - Iron is an essential element for nervous system development, and maintaining a
      normal iron level in nervous system is controlled by multiple factors. Recent
      studies reported that iron dysregulation and the following iron metabolic
      pathways played an important role in hypoxic ischemic brain damage (HIBD) in
      neonates. Circulatory iron level is altered after hypoxia-ischemia exposure,
      which may cause abnormal iron deposition in the nervous system followed by
      neuronal injury. Finding the causing factors for abnormal iron metabolism after
      hypoxia-ischemia exposure, as well as understanding the mechanisms how iron
      metabolism contributes to HIBD, will shed lights on HIBD prevention and
      treatment. In this mini-review, we summarized changes in iron metabolism after
      neonatal hypoxia-ischemia exposure, its possible regulatory factors and how iron
      abnormalities contribute to HIBD.

PMID- 28435982
TI  - [Changes in biological functions of high-density lipoprotein after abnormal
      modification].
AB  - High-density lipoprotein (HDL) is composed of apolipoproteins, lipids and
      functional proteins. HDL protects against atherosclerosis (AS) by reverse
      cholesterol transport (RCT). HDL inhibits the lipid oxidation, inflammation and
      restores endothelial function. During systemic inflammation or metabolic
      disorders, HDL can be modified abnormally and converted to a dysfunctional type,
      which results in the loss of anti-inflammatory factors including apolipoprotein A
      I (apoA-I), paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF
      AH), and gains of pro-inflammatory factors such as serum amyloid A (SAA),
      triglyceride (TG) and oxidative lipid. Therefore, understanding the changes in
      compositions and biological functions of dysfunctional HDL might help to
      comprehend its pathogenic mechanism.

PMID- 28435983
TI  - [Effect of high altitude hypoxia on fetal development during pregnancy and the
      reason analysis].
AB  - High altitude hypoxia is an important factor to affect fetal development during
      pregnancy. In the special environment, maternal physiological functions are
      regulated to maintain the maternal and fetal homeostasis, so that limited oxygen
      is to meet the needs of fetal growth and development. In this review, the
      literatures about the effects of hypoxic environment on fetal development during
      pregnancy in recent years were summarized, in which the fetal growth
      characteristics, maternal physiological regulation, genetic and placental
      influencing factors in high altitude areas were involved. This may be helpful for
      the reproductive healthcare of women in high altitude region, and also for the
      treatment and prevention of fetal growth retardation in the hypoxic environment.

PMID- 28435984
TI  - Patterns, predictors and persistence of chronic sedative use: a population-based
      observational study of older adults in British Columbia, Canada.
AB  - BACKGROUND: Benzodiazepines and benzodiazepine-like sedatives (zopiclone,
      zolpidem and zaleplon) are commonly prescribed to treat anxiety and insomnia but
      are contraindicated for chronic use. We sought to study the persistence, over
      multiple years, of chronic use of benzodiazepines and benzodiazepine-like
      sedatives among community-dwelling adults in British Columbia, Canada. METHODS:
      This is a retrospective analysis of linked health data for adults aged 50 to 69
      in 2004 who resided in British Columbia, Canada, between 2004 and 2013. We
      assigned subjects to one of four groups according to the total number of days of
      benzodiazepines and benzodiazepine-like sedatives that they were dispensed from
      retail pharmacies in each observation year. We estimated logistic regression
      models to measure associations between the odds of chronic sedative use and
      explanatory variables. We computed transition probability matrices that depict
      likelihood of changes in sedative utilization levels across years. RESULTS:
      Nearly one in ten (9.4%) community-dwelling older adults in British Columbia
      filled prescriptions with more than 90 days' worth of benzodiazepines or
      benzodiazepine-like sedatives in 2013. The odds of such chronic sedative use were
      higher for people who were older, had lower income, were sicker, or lived in
      rural communities; odds were lower for people with Chinese or South Asian
      surnames and for men who were married. Controlling for other factors, chronic
      users of sedatives in 2008 were 15 times more likely than non-users of sedatives
      in 2008 to be chronic sedative users in 2013 (OR = 14.73; 95% CI = [14.24,
      15.24]). Approximately two out of every five older British Columbians who were
      chronic sedative users in 2013 had been chronic users of sedatives 10 years
      prior. Two out of every three chronic sedative users in 2004 were either chronic
      users (57%) or dead (16%) by 2013. INTERPRETATION: Chronic use of sedatives is
      prevalent and persistent among older adults in British Columbia. The persistence
      of chronic sedative use between when patients were 50 to 59 years old and when
      they were 60 to 69 years old suggests that earlier interventions to curb chronic
      sedative use may be warranted even if patients do not experience significant
      risks until later ages.

PMID- 28435985
TI  - Elucidating the Abeta42 Anti-Aggregation Mechanism of Action of Tramiprosate in
      Alzheimer's Disease: Integrating Molecular Analytical Methods, Pharmacokinetic
      and Clinical Data.
AB  - BACKGROUND: Amyloid beta (Abeta) oligomers play a critical role in the
      pathogenesis of Alzheimer's disease (AD) and represent a promising target for
      drug development. Tramiprosate is a small-molecule Abeta anti-aggregation agent
      that was evaluated in phase III clinical trials for AD but did not meet the
      primary efficacy endpoints; however, a pre-specified subgroup analysis revealed
      robust, sustained, and clinically meaningful cognitive and functional effects in
      patients with AD homozygous for the epsilon4 allele of apolipoprotein E4 (APOE4/4
      homozygotes), who carry an increased risk for the disease. Therefore, to build on
      this important efficacy attribute and to further improve its pharmaceutical
      properties, we have developed a prodrug of tramiprosate ALZ-801 that is in
      advanced stages of clinical development. To elucidate how tramiprosate works, we
      investigated its molecular mechanism of action (MOA) and the translation to
      observed clinical outcomes. OBJECTIVE: The two main objectives of this research
      were to (1) elucidate and characterize the MOA of tramiprosate via an integrated
      application of three independent molecular methodologies and (2) present an
      integrated translational analysis that links the MOA, conformation of the target,
      stoichiometry, and pharmacokinetic dose exposure to the observed clinical outcome
      in APOE4/4 homozygote subjects. METHOD: We used three molecular analytical
      methods-ion mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic
      resonance (NMR), and molecular dynamics-to characterize the concentration-related
      interactions of tramiprosate versus Abeta42 monomers and the resultant
      conformational alterations affecting aggregation into oligomers. The molecular
      stoichiometry of the tramiprosate versus Abeta42 interaction was further analyzed
      in the context of clinical pharmacokinetic dose exposure and central nervous
      system Abeta42 levels (i.e., pharmacokinetic-pharmacodynamic translation in
      humans). RESULTS: We observed a multi-ligand interaction of tramiprosate with
      monomeric Abeta42, which differs from the traditional 1:1 binding. This resulted
      in the stabilization of Abeta42 monomers and inhibition of oligomer formation and
      elongation, as demonstrated by IMS-MS and molecular dynamics. Using NMR
      spectroscopy and molecular dynamics, we also showed that tramiprosate bound to
      Lys16, Lys28, and Asp23, the key amino acid side chains of Abeta42 that are
      responsible for both conformational seed formation and neuronal toxicity. The
      projected molar excess of tramiprosate versus Abeta42 in humans using the dose
      effective in patients with AD aligned with the molecular stoichiometry of the
      interaction, providing a clear clinical translation of the MOA. A consistent
      alignment of these preclinical-to-clinical elements describes a unique example of
      translational medicine and supports the efficacy seen in symptomatic patients
      with AD. This unique "enveloping mechanism" of tramiprosate also provides a
      potential basis for tramiprosate dose selection for patients with homozygous AD
      at earlier stages of disease. CONCLUSION: We have identified the molecular
      mechanism that may account for the observed clinical efficacy of tramiprosate in
      patients with APOE4/4 homozygous AD. In addition, the integrated application of
      the molecular methodologies (i.e., IMS-MS, NMR, and thermodynamics analysis)
      indicates that it is feasible to modulate and control the Abeta42 conformational
      dynamics landscape by a small molecule, resulting in a favorable Abeta42
      conformational change that leads to a clinically relevant amyloid anti
      aggregation effect and inhibition of oligomer formation. This novel enveloping
      MOA of tramiprosate has potential utility in the development of disease-modifying
      therapies for AD and other neurodegenerative diseases caused by misfolded
      proteins.

PMID- 28435986
TI  - Asian consortium on radiation dose of pediatric cardiac CT (ASCI-REDCARD).
AB  - BACKGROUND: With incremental utilization of pediatric cardiac CT in congenital
      heart disease, it is imperative to define its current radiation dose levels in
      clinical practice in order to help imagers optimize CT protocols, particularly in
      Asia and other developing countries where CT physicists are not readily
      available. OBJECTIVE: To evaluate current radiation dose levels and influencing
      factors in cardiac CT in children with congenital heart disease in Asia by
      conducting a retrospective multi-center, multi-vendor study. MATERIALS AND
      METHODS: We included 1,043 pediatric cardiac CT examinations performed in 8
      centers between January 2014 and December 2014 to evaluate congenital heart
      disease. In five weight groups, we calculated radiation dose metrics including
      volume CT dose index, size-specific dose estimate, dose-length product and
      effective dose. Age at CT exam, gender, tube voltage, scan mode, CT indication
      and image reconstruction algorithm were analyzed to learn whether they influenced
      CT radiation dose. RESULTS: Volume CT dose index, size-specific dose estimate,
      dose-length product and effective dose of pediatric cardiac CT showed variations
      in the range of 4.3-23.8 mGy, 4.9-17.6 mGy, 55.8-501.3 mGy?cm and 1.5-3.2 mSv,
      respectively, within five weight groups. Gender, tube voltage, scan mode and
      cardiac function assessment significantly influenced CT radiation dose.
      CONCLUSION: This multi-center, multi-vendor study demonstrated variations in
      radiation dose metrics of pediatric cardiac CT reflecting current practice in
      Asia. Gender, tube voltage, scan mode and cardiac function assessment should be
      considered as essential radiation dose-influencing factors in developing optimal
      pediatric cardiac CT protocols.

PMID- 28435987
TI  - Rethinking the usefulness of bone marrow biopsy on treatment decision in CLL
      patients at diagnosis.
AB  - We aimed to investigate the role of bone marrow infiltration pattern (BMIP) and
      bone marrow reticulin fibrosis (BMRF) in determining treatment demand in patients
      with diagnosis of chronic lymphocytic leukemia (CLL). We retrospectively
      evaluated the data of 65 patients, who were followed with the diagnosis of CLL at
      Istanbul Training and Research Hospital, Department of Hematology, between July
      2007 and June 2016. The median age of the patients was 64 years (range, 32-83).
      Twenty-three (35.4%) patients were female, and 42 (64.6%) were male. Early/mild
      grade BMRF was observed in 46 (70.8%) patients and advanced grade BMRF in 19
      (29.2%) patients. Eleven (23.9%) of 46 patients with early/mild grade BMRF and 10
      (52.9%) of 19 patients with advanced grade BMRF required treatment during follow
      up (p = 0.04). According to the BMIP, 14 (21.5%) patients had diffuse and 51
      (78.5%) patients had non-diffuse BMIP. Eleven (78.6%) of 14 patients with diffuse
      BMIP and 10 (19.6%) of 51 patients with non-diffuse BMIP required treatment
      during follow-up (p < 0.001). In univariate analysis, both advanced grade BMRF
      and diffuse BMIP had an impact on occurrence of treatment demand (p = 0.028, HR =
      3.535 vs. p < 0.01 HR = 15.033). Multivariate analysis also revealed diffuse BMIP
      to be effective (p < 0.001, HR 13.089), while advanced grade BMRF failed to
      significantly influence treatment demand (p = 0.140, HR 2.664). In conclusion, in
      the light of our findings, it is reasonable to consider that bone marrow biopsy
      at the time of diagnosis might provide a preliminary information about treatment
      demand in patients with CLL.

PMID- 28435988
TI  - The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and
      Pancreatic Cancer Can be Therapeutic Targets.
AB  - An important question in systems biology is what role the underlying molecular
      mechanisms play in disease progression. The relationship between chronic
      pancreatitis and pancreatic cancer needs further exploration in a system view. We
      constructed the disease network based on gene expression data and protein-protein
      interaction. We proposed an approach to discover the underlying core network and
      molecular factors in the progression of pancreatic diseases, which contain stages
      of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and
      pancreatic cancer core network and key factors were revealed and then verified by
      gene set enrichment analysis of pathways and diseases. The key factors provide
      the microenvironment for tumor initiation and the change of gene expression level
      of key factors bridge chronic pancreatitis and pancreatic cancer. Some new
      candidate genes need further verification by experiments. Transcriptome profiling
      based network analysis reveals the importance of chronic pancreatitis genes and
      pathways in pancreatic cancer development on a system level by computational
      method and they can be therapeutic targets.

PMID- 28435989
TI  - Aggressive medical management of acute traumatic subdural hematomas before
      emergency craniotomy in patients presenting with bilateral unreactive pupils. A
      cohort study.
AB  - BACKGROUND: The outcome of patients with severe traumatic brain injury (TBI) and
      acute traumatic subdural hematoma (aSDH) admitted to the emergency room with
      bilaterally dilated, unreactive pupils (bilateral mydriasis) is notoriously poor.
      METHODS: Of 2074 TBI patients consecutively admitted to our facility between 1997
      and 2012, 115 had a first CT scan with aSDH, unreactive bilateral mydriasis, and
      a Glasgow Coma Score of 3 or 4. Sixty-two patients were unoperated and died
      within hours or a few days. The remaining 53 patients (2.5% of the 2074
      consecutive patients) were scheduled for emergent evacuation of the aSDH. We
      compared three different dosages of mannitol to landmark different comprehensive
      levels of treatment: (1) a "basic" level of treatment characterized by a single
      conventional dose (18 to 36 g), (2) "reinforced" treatment landmarked by a single
      high dose (54 to 72 g), and (3) "aggressive" treatment landmarked by a single
      high dose (90 to 106 g). Doses above 36 g were administered intravenously over a
      period of 5 min. RESULTS: Of the 53 selected patients, 7 were aggressively
      managed (13.2%) and 24 (45.3%) received reinforced treatment. Rates of
      hyperventilation and barbiturate bolus administration were appropriately
      associated with increasing doses of mannitol. After adjustment for age,
      aggressive management was significantly associated with a lower risk of death and
      persistent vegetative state [adjusted OR 0.016 (95% 0.001-0.405)]. Patients
      surviving after aggressive management suffered more severe disability at 1 year.
      CONCLUSION: The study shows an association between reduced mortality and
      persistent vegetative state, albeit at the cost of increased long-term severe
      disability in survivors, and aggressive medical preoperative management of
      mydriatic patients with aSDH following TBI.

PMID- 28435990
TI  - QSAR modeling for predicting mutagenic toxicity of diverse chemicals for
      regulatory purposes.
AB  - The safety assessment process of chemicals requires information on their
      mutagenic potential. The experimental determination of mutagenicity of a large
      number of chemicals is tedious and time and cost intensive, thus compelling for
      alternative methods. We have established local and global QSAR models for
      discriminating low and high mutagenic compounds and predicting their mutagenic
      activity in a quantitative manner in Salmonella typhimurium (TA) bacterial
      strains (TA98 and TA100). The decision treeboost (DTB)-based classification QSAR
      models discriminated among two categories with accuracies of >96% and the
      regression QSAR models precisely predicted the mutagenic activity of diverse
      chemicals yielding high correlations (R 2) between the experimental and model
      predicted values in the respective training (>0.96) and test (>0.94) sets. The
      test set root mean squared error (RMSE) and mean absolute error (MAE) values
      emphasized the usefulness of the developed models for predicting new compounds.
      Relevant structural features of diverse chemicals that were responsible and
      influence the mutagenic activity were identified. The applicability domains of
      the developed models were defined. The developed models can be used as tools for
      screening new chemicals for their mutagenicity assessment for regulatory purpose.

PMID- 28435991
TI  - Polycythemia, capillary rarefaction, and focal glomerulosclerosis in two
      adolescents born extremely low birth weight and premature.
AB  - BACKGROUND: Low birthweight infants have a reduced number of nephrons and are at
      high risk of chronic kidney disease. Preterm birth and/or intrauterine growth
      restriction (IUGR) may also affect peritubular capillary development, as has been
      shown in other organs. CASE-DIAGNOSIS/TREATMENT: We report two patients with a
      history of preterm birth and extremely low birthweight who showed polycythemia
      and renal capillary rarefaction. Patient 1 and 2, born at 25 weeks of gestation
      with a birthweight of 728 and 466 g, showed mild proteinuria at age 8 and 6
      years, respectively. In addition to increasing proteinuria, hemoglobin levels
      became elevated towards adolescence and their serum erythropoietin (EPO) was high
      despite polycythemia. Light microscopic examination of renal biopsy specimens
      showed glomerular hypertrophy, focal segmental glomerulosclerosis, and only mild
      tubulointerstitial fibrosis. A decrease in the immunohistochemical staining of
      CD31 and CD34 endothelial cells in renal biopsy specimens was consistent with
      peritubular capillary rarefaction. CONCLUSIONS: Since kidney function was almost
      normal and fibrosis was not severe, we consider that the capillary rarefaction
      and polycythemia associated with elevated EPO levels were largely attributable to
      preterm birth and/or IUGR.

PMID- 28435992
TI  - Elevated Plasma S100B, Psychotic Symptoms, and Cognition in Schizophrenia.
AB  - S100B is a calcium binding protein mainly produced by glial cells. Previous
      studies have shown elevated levels of S100B in patients with schizophrenia. We
      measured S100B levels in fasting plasma of 39 patients with schizophrenia and 19
      adult healthy controls. We used linear regression to compare S100B between
      patients and controls. In patients only, we also investigated the relationship
      between S100B levels and psychotic symptoms (assessed by the Positive and
      Negative Syndrome Scale), and cognitive function (assessed by the NIH Toolbox
      Cognition Battery), respectively by calculating Pearson's correlation
      coefficients. Mean plasma S100B was significantly higher in the patient group
      than in the control group. There were no significant correlations between plasma
      S100B and psychotic symptoms or cognition.

PMID- 28435993
TI  - Mumps Associated Acute Motor Axonal Polyneuropathy.

PMID- 28435994
TI  - Thalassemia Minor and Major: Current Management.
AB  - Thalassemia is a common genetic disorder. It has been estimated that in India
      nearly 5 crore people are thalassemia carriers. They are asymptomatic and are
      detected on blood tests. These people are at same risk of developing iron
      deficiency anemia as general population and need iron therapy in the presence of
      iron deficiency anemia. Nearly 12,000 children with thalassemia major (Homozygous
      state) are born every year. These children often present with significant anemia
      along with hepatosplenomegaly during infancy and require early diagnosis and
      institution of therapy with repeated blood transfusions and chelation therapy.
      Adequate dose of chelation therapy is essential to maintain serum ferritin around
      1000 ng/ml. With present protocol of management, thalassemic children have near
      normal life. Bone marrow transplantation offers cure for these children; results
      of bone marrow transplantation are best when performed below 7 y of age.

PMID- 28435995
TI  - Hereditary Homozygous C3 Deficiency.

PMID- 28435996
TI  - Cognitive Effects of Air Pollution Exposures and Potential Mechanistic
      Underpinnings.
AB  - PURPOSE OF REVIEW: This review sought to address the potential for air pollutants
      to impair cognition and mechanisms by which that might occur. RECENT FINDINGS:
      Air pollution has been associated with deficits in cognitive functions across a
      wide range of epidemiological studies, both with developmental and adult
      exposures. Studies in animal models are significantly more limited in number,
      with somewhat inconsistent findings to date for measures of learning, but show
      more consistent impairments for short-term memory. Potential contributory
      mechanisms include oxidative stress/inflammation, altered levels of dopamine
      and/or glutamate, and changes in synaptic plasticity/structure. Epidemiological
      studies are consistent with adverse effects of air pollutants on cognition, but
      additional studies and better phenotypic characterization are needed for animal
      models, including more precise delineation of specific components of cognition
      that are affected, as well as definitions of critical exposure periods for such
      effects and the components of air pollution responsible. This would permit
      development of more circumscribed hypotheses as to potential behavioral and
      neurobiological mechanisms.

PMID- 28435997
TI  - Assessment of organic pollution of an industrial river by synchronous
      fluorescence and UV-vis spectroscopy: the Fensch River (NE France).
AB  - To rapidly monitor the surface water quality in terms of organic pollution of an
      industrial river undergoing restoration, optical methods (UV-visible spectrometry
      and fluorescence) were applied in parallel to classical physical-chemical
      analyses. UV-visible spectra were analyzed using the maximum of the second
      derivative at 225 nm (related to nitrates), specific absorbance at 254 nm
      (SUVA254), and the spectral slope between 275 and 295 nm (S 275-295) (related to
      the aromaticity and molecular weight of dissolved organic carbon). The
      synchronous fluorescence spectra (wavelength difference = 50 nm) exhibited a high
      variability in the composition of dissolved organic material between the upstream
      and downstream sections and also versus time. The principal components analysis
      of the entire set of synchronous fluorescence spectra helped to define three
      river sections with different pollution characteristics. Spectral decomposition
      was applied to the two most upstream sections: five fluorophores, classical in
      rivers impacted by domestic sewage and related to protein-like (lambda ex = 280
      nm) and humic-like fluorescence (M-type with lambda ex ~ 305-310 nm and C-type
      with lambda ex >= 335 nm), were identified. The irregular shape of the
      synchronous fluorescence spectra in the most downstream section is likely due to
      organic pollutants of industrial origin; however, their variability and the
      complexity of the spectra did not allow the further elucidation of their nature.

PMID- 28435998
TI  - A 6-year-old boy with Wilson disease-A diagnostic dilemma.
AB  - A 6-year-old boy presented with 2 months history of progressive abdominal
      distension and jaundice. He was deeply icteric with ascites, hepatosplenomegaly,
      hyperbilirubinemia, raised transaminases, and coagulopathy. Viral markers and
      slit lamp examination for Kayser-Fleischer ring were negative. Serum
      ceruloplasmin and 24-h urinary copper post-D-pencillamine challenge were normal.
      Anti-smooth muscle antibody was positive 1:20, and liver biopsy showed
      micronodular cirrhosis with abundant Mallory hyaline and stainable copper
      deposits. The liver histology was indicative of Indian childhood cirrhosis,
      whereas the presence of autoantibodies, elevated transaminases, and increased
      globulin was suggestive of autoimmune hepatitis. Gene studies identified p.R969Q
      mutation in ATP7B gene, which solved the dilemma and confirmed the diagnosis of
      Wilson disease (WD). We report a clinicopathological conference of this boy to
      highlight the challenges faced by pediatricians in the diagnosis of Wilson
      disease. ?.

PMID- 28436000
TI  - FoxO3a suppression and VPS34 activity are essential to anti-atrophic effects of
      leucine in skeletal muscle.
AB  - Our aim is to gain insight into the mechanisms underlying the anti-atrophic
      effects of leucine, namely, the way that this amino acid can restrain the up
      regulation of MuRF1 and Mafbx/Atrogin-1 in muscle atrophy. Male rats received
      dietary leucine supplementation for 1-3 days, during which time their hind limbs
      were immobilized. Our results showed that leucine inhibited Forkhead Box O3
      (FoxO3a) translocation to cell nuclei. In addition, leucine was able to reverse
      the expected reduction of FoXO3a ubiquitination caused by immobilization.
      Unexpectedly, leucine promoted these effects independently of the Class I
      PI3K/Akt pathway. Vacuolar protein sorting 34 (VPS34; a Class III PI3K) was
      strongly localized in nuclei after immobilization and leucine supplementation was
      able to prevent this effect. In experiments on cultured primary myotubes,
      dexamethasone led to the localization of VPS34 in the nucleus. In addition, the
      pharmacological inhibition of VPS34 blocked VPS34 nuclear localization and
      impaired the protective effect of leucine upon myotube trophicity. Finally, the
      pharmacological inhibition of VPS34 in primary myotubes prevented the protective
      effects of leucine upon MuRF1 and Mafbx/Atrogin-1 gene expression. Autophagy
      related target genes were not responsive to leucine. Thus, we demonstrate that
      the anti-atrophic effect of leucine is dependent upon FoxO3a suppression and
      VPS34 activity.

PMID- 28435999
TI  - Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins
      and Increases Stereotypic and Anxyolitic Behavior in Adult Rats.
AB  - Propofol is a general anesthetic commonly used in pediatric clinical practices.
      Experimental findings demonstrate that anesthetics induce widespread apoptosis
      and cognitive decline in a developing brain. Although anesthesia-mediated
      neurotoxicity is the most prominent during intense period of synaptogenesis, the
      effects of an early anesthesia exposure on the synapses are not well understood.
      The aim of this study was to examine the effects of neonatal propofol anesthesia
      on the expression of key proteins that participate in synaptogenesis and synaptic
      plasticity and to evaluate long-term neurobehavioral abnormalities in the mature
      adult brain. Propofol-injected 7-day-old rats were maintained under 2-, 4-, and 6
      h-long anesthesia and sacrificed 0, 4, 16, and 24 h after the termination of each
      exposure. We showed that propofol anesthesia strongly influenced spatiotemporal
      expression and/or proteolytic processing of crucial presynaptic (GAP-43,
      synaptophysin, alpha-synuclein), trans-synaptic (N-cadherin), and postsynaptic
      (drebrin, MAP-2) proteins in the cortex and thalamus. An overall decrease of
      synaptophysin, alpha-synuclein, N-cadherin, and drebrin indicated impaired
      function and structure of the synaptic contacts immediately after anesthesia
      cessation. GAP-43 and MAP-2 adult and juvenile isoforms are upregulated following
      anesthesia, suggesting compensatory mechanism in the maintaining of the
      structural integrity and stabilization of developing axons and dendritic arbors.
      Neonatal propofol exposure significantly altered spontaneous motor activity
      (increased stereotypic/repetitive movements) and changed emotional behavior
      (reduced anxiety-like response) in the adulthood, 6 months later. These findings
      suggest that propofol anesthesia is synaptotoxic in the developing brain,
      disturbing synaptic dynamics and producing neuroplastic changes permanently
      incorporated into existing networks with long-lasting functional consequences.

PMID- 28436001
TI  - Gait instability in valproate-treated patients: Call to measure ammonia levels.
AB  - OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to
      several neurological and systemic symptoms as well as to seizure exacerbation.
      Gait instability and recurrent falls are rarely mentioned as symptoms, especially
      not as predominant ones. METHODS: We report five adult patients with frontal lobe
      epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was
      unstable gait and falls. RESULTS: There were four males and one female patients
      with FLE, 25-42-year-old, three following epilepsy surgery. All of them were
      treated with antiepileptic drug polytherapy. Gait instability with falls was one
      of the principal sequelae of the treatment. Patients also exhibited mild
      encephalopathy (all patients) and flapping tremor (three patients) that developed
      following the addition of VPA (three patients) and with chronic VPA treatment
      (two patients). VPA levels were within the reference range. Serum ammonia levels
      were significantly elevated (291-407 MUmole/L, normal 20-85) with normal or
      slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the
      return of ammonia levels to normal and resolution of the clinical symptoms,
      including seizures, which disappeared in two patients and either decreased in
      frequency or became shorter in duration in the other three. CONCLUSIONS: Gait
      instability due to hyperammonemia and VPA treatment is probably under-recognized
      in many patients. It can develop when the VPA levels are within the reference
      range and with normal or slightly elevated liver enzymes.

PMID- 28436003
TI  - Bio-CoDa: A new analysis class to ensure accurate and precise monoclonal antibody
      CQA estimation and control.
AB  - Monoclonal antibody production processes control critical quality attributes
      (CQAs), which are the measures that provide proof of a product's identity and
      quality. Critical decisions rely on the accuracy and precision of these measures,
      as well as their appropriate statistical treatment. Many measures require special
      attention. For example, the charge heterogeneity CQA measured by ionic exchange
      chromatography reports proportions or percentages of the total integrated peak
      area of known species. Since proportions sum to a constant (1 or 100%), they fall
      into a special class of data called compositional data that have a unit sum
      constraint and therefore an inherent correlation. However, these measures are
      often analyzed assuming independence which is incorrect. Estimating statistics
      with incorrect assumptions can lead to inferential failures (e.g., shelf life
      failures), or can lead to missing important structural patterns in the data.
      Presented here is a new class of analysis methods for CQAs compositional data
      called Biologic Compositional Data Analysis (Bio-CoDa). The method is based on
      the elegant solution to analysis issues by Aitchison (1986). An introduction to
      the Bio-CoDa methods with rational is presented as well as examples demonstrating
      its strengths. Biotechnol. Bioeng. 2017;114: 2001-2010. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28436002
TI  - Characterization of the chondrocyte secretome in photoclickable poly(ethylene
      glycol) hydrogels.
AB  - Poly(ethylene glycol) (PEG) hydrogels are highly tunable platforms that are
      promising cell delivery vehicles for chondrocytes and cartilage tissue
      engineering. In addition to characterizing the type of extracellular matrix (ECM)
      that forms, understanding the types of proteins that are secreted by encapsulated
      cells may be important. Thus, the objectives for this study were to characterize
      the secretome of chondrocytes encapsulated in PEG hydrogels and determine whether
      the secretome varies as a function of hydrogel stiffness and culture condition.
      Bovine chondrocytes were encapsulated in photoclickable PEG hydrogels with a
      compressive modulus of 8 and 46 kPa and cultured under free swelling or dynamic
      compressive loading conditions. Cartilage ECM deposition was assessed by
      biochemical assays and immunohistochemistry. The conditioned medium was analyzed
      by liquid chromatography-tandem mass spectrometry. Chondrocytes maintained their
      phenotype within the hydrogels and deposited cartilage-specific ECM that
      increased over time and included aggrecan and collagens II and VI. Analysis of
      the secretome revealed a total of 64 proteins, which were largely similar among
      all experimental conditions. The identified proteins have diverse functions such
      as biological regulation, response to stress, and collagen fibril organization.
      Notably, many of the proteins important to the assembly of a collagen-rich
      cartilage ECM were identified and included collagen types II(alpha1), VI (alpha1,
      alpha2, and alpha3), IX (alpha1), XI (alpha1 and alpha2), and biglycan. In
      addition, many of the other identified proteins have been reported to be present
      within cell-secreted exosomes. In summary, chondrocytes encapsulated within
      photoclickable PEG hydrogels secrete many types of proteins that diffuse out of
      the hydrogel and which have diverse functions, but which are largely preserved
      across different hydrogel culture environments. Biotechnol. Bioeng. 2017;114:
      2096-2108. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436004
TI  - Engineering of an H2 O2 auto-scavenging in vivo cascade for pinoresinol
      production.
AB  - Pinoresinol is a natural lignan with a high market value that has potential
      pharmacological and food supplement applications. Pinoresinol is currently
      isolated from plants, which suffers from low efficiency and yield. To produce
      pinoresinol from inexpensive and industrially available eugenol, an in vivo
      enzymatic cascade composed of vanillyl alcohol oxidase and peroxidase was
      designed, which scavenges H2 O2 automatically and eliminates protein purification
      and cofactor addition. Two peroxidases were screened and identified from
      Escherichia coli BL21 (DE3), and tested in the enzymatic cascade. To balance the
      flux, different genetic architectures were constructed by using ePathBrick and
      fusion gene approaches. Scavenging H2 O2 alleviated by-product toxicity and
      enzyme inhibition, and led to efficient pinoresinol production. Optimization of
      the reaction conditions achieved a titer of 11.29 g/L pinoresinol. The molar
      yield and productivity were 52.77% and 1.03 g/(L * h), respectively. The elegant
      strategy developed herein utilizes the harmful by-product to drive the
      biosynthetic reaction forward and simultaneously detoxify cells, thereby
      preventing enzyme inhibition. Biotechnol. Bioeng. 2017;114: 2066-2074. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28436005
TI  - Fast and reliable strain characterization of Streptomyces lividans through micro
      scale cultivation.
AB  - Filamentous organisms of the genus Streptomyces play an important role in
      industrial production processes, due to their extensive secondary metabolism
      variability, as well as their ability to secrete efficiently large amounts of
      (heterologous) proteins. While genetic engineering tools are available to rapidly
      build up large strain libraries, the subsequent strain screening and bioprocess
      development still constitutes a bottleneck. This is due to the lack of reliable
      parallelized and accelerated cultivation techniques for morphologically
      challenging organisms. To address this challenge, we developed an integrated
      cultivation workflow for Streptomyces lividans based on a parallelized shaken 48
      well microtiter-plate (MTP) cultivation device. In a first step, a feasible pre
      culture method was identified and validated, revealing high comparability in
      subsequent main cultivations (coefficient of variation of 1.1% for in-plate
      replicates and 3.2% between different pre-cultures). When validating the growth
      performance in 1 mL MTP cultivation against an established 1,000 mL lab-scale
      cultivation system, highly comparable cultivation patterns were found for online
      (pH, dissolved oxygen), as well as for offline derived parameters (glucose
      uptake, cell-dry-weight, and pellet size). Additionally, the two cultivation
      regimes were compared with respect to transcriptional and protein secretion
      activity of Streptomyces, showing overall good comparability with minor, but well
      explainable discrepancies, most probably caused by different energy dissipation
      (shaking vs. stirring) and adaption effects due to different illumination
      conditions. Embedded within the presented cultivation workflow, the 1 mL MTP
      based parallelized cultivation system seems to be a suitable screening tool for
      filamentous and industrial relevant organisms like Streptomyces. This can
      contribute to widen the field of application for these organisms and facilitate
      screening and early-stage bioprocess development. Biotechnol. Bioeng. 2017;114:
      2011-2022. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436006
TI  - Good Cop, Better Cop: Evaluation of a Geriatrics Training Program for Police.
AB  - OBJECTIVES: To develop, implement, and evaluate a training program in aging
      related health for police officers. DESIGN: Cross-sectional. SETTING: Crisis
      intervention training program for police officers in San Francisco. PARTICIPANTS:
      Police officers attending one of five 2-hour trainings (N = 143). INTERVENTION: A
      lecture on aging-related health conditions pertinent to police work followed by
      three experiential trainings on how it feels to be "old." MEASUREMENTS:
      Participants evaluated the quality of the training and the likelihood that they
      would apply new knowledge to their work and rated their knowledge using a
      retrospective pre-post evaluation. In open-ended responses, participants reported
      work-related changes they anticipated making in response to the training.
      RESULTS: All 143 participants completed the evaluation. Eighty-four percent
      reported interacting with older adults at least monthly; 45% reported daily
      interactions. Participants rated the training quality at 4.6/5 and the likelihood
      they would apply new knowledge to their work at 4.4/5. Retrospective pre-post
      knowledge scores increased for all domains, including how to identify aging
      related health conditions that can affect safety during police interactions
      (2.9/5 to 4.2/5; P < .001). In open-ended responses, participants anticipated
      having more empathy for and awareness of aging-related conditions and greater
      ability to provide older adults with appropriate community referrals. CONCLUSION:
      A brief training in aging-related health significantly increased police officers'
      self-reported knowledge and skills. Clinicians have an important opportunity to
      help enhance safe and effective community policing for older adults.

PMID- 28436007
TI  - Overexpression of the regulatory subunit of glutamate-cysteine ligase enhances
      monoclonal antibody production in CHO cells.
AB  - For decades, Chinese hamster ovary (CHO) cells have been the preferred host for
      therapeutic monoclonal antibody (mAb) production; however, increasing mAb titer
      by rational engineering remains a challenge. Our previous proteomic analysis in
      CHO cells suggested that a higher content of glutathione (GSH) might be related
      to higher productivity. GSH is an important antioxidant, cell detoxifier, and is
      required to ensure the formation of native disulfide bonds in proteins. To
      investigate the involvement of GSH in mAb production, we generated stable CHO
      cell lines overexpressing genes involved in the first step of GSH synthesis;
      namely the glutamate-cysteine ligase catalytic subunit (Gclc) and the glutamate
      cysteine ligase modifier subunit (Gclm). The two genes were reconstructed from
      our RNA-Seq de novo assembly and then were functionally annotated. Once the
      sequences of the genes were confirmed using proteogenomics, a transiently
      expressed mAb was introduced into cell lines overexpressing either Gclc or Gclm.
      The new cell lines were compared for mAb production to the parental cell line and
      changes at the proteome level were measured using SWATH. As per our previous
      proteomics observations, overexpressing Gclm improved productivity, titer, and
      the frequency of high producer clones by 70%. In contrast, overexpressing Gclc,
      which produced a higher amount of GSH, did not increase mAb production. We show
      that GSH cannot be linked to higher productivity and that Gclm may be controlling
      other cellular processes involved in mAb production yet to be elucidated.
      Biotechnol. Bioeng. 2017;114: 1825-1836. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436008
TI  - A sea urchin in vivo model to evaluate Epithelial-Mesenchymal Transition.
AB  - Epithelial-mesenchymal transition (EMT) is an evolutionarily conserved cellular
      program, which is a prerequisite for the metastatic cascade in carcinoma
      progression. Here, we evaluate the EMT process using the sea urchin Paracentrotus
      lividus embryo. In sea urchin embryos, the earliest EMT event is related to the
      acquisition of a mesenchymal phenotype by the spiculogenetic primary mesenchyme
      cells (PMCs) and their migration into the blastocoel. We investigated the effect
      of inhibiting the epidermal growth factor (EGF) signaling pathway on this
      process, and we observed that mesenchyme cell differentiation was blocked. In
      order to extend and validate our studies, we investigated the migratory
      capability and the level of potential epidermal growth factor receptor (EGFr)
      targets in a breast cancer cell line after EGF modulation. Altogether, our data
      highlight the sensitivity of the sea urchin embryo to anti-EMT drugs and pinpoint
      the sea urchin embryo as a valuable in vivo model system for studying EMT and the
      screening of anti-EMT candidates.

PMID- 28436009
TI  - A wake-up call to dermatologists - climate change affects the skin.

PMID- 28436010
TI  - Serratia marcescens: an Italian story.

PMID- 28436012
TI  - Prostate cancer in black men: Is it time for personalized screening approaches?

PMID- 28436013
TI  - Chronic, unilateral, and erythematous lesions on the foot of a pediatric patient 
      a clinicopathological challenge.

PMID- 28436011
TI  - Is prostate cancer different in black men? Answers from 3 natural history models.
AB  - BACKGROUND: Black men in the United States have substantially higher prostate
      cancer incidence rates than the general population. The extent to which this
      incidence disparity is because prostate cancer is more prevalent, more
      aggressive, and/or more frequently diagnosed in black men is unknown. METHODS:
      The authors estimated 3 independently developed models of prostate cancer natural
      history in black men and in the general population using an updated
      reconstruction of prostate-specific antigen screening, based on the National
      Health Interview Survey in 2005 and on prostate cancer incidence data from the
      Surveillance, Epidemiology, and End Results program during 1975 through 2000. By
      using the estimated models, the natural history of prostate cancer was compared
      between black men and the general population. RESULTS: The models projected that
      from 30% to 43% (range across models) of black men develop preclinical prostate
      cancer by age 85 years, a risk that is (relatively) 28% to 56% higher than that
      in the general population. Among men who had preclinical disease onset, black men
      had a similar risk of diagnosis (range, 35%-49%) compared with the general
      population (32%-44%), but their risk of progression to metastatic disease by the
      time of diagnosis was from 44% to 75% higher than that in the general population.
      CONCLUSIONS: Prostate cancer incidence patterns implicate higher incidence of
      preclinical disease and higher risk of metastatic progression among black men.
      The findings suggest screening black men earlier than white men and support
      further research into the benefit-harm tradeoffs of more aggressive screening
      policies for black men. Cancer 2017;123:2312-2319. (c) 2017 American Cancer
      Society.

PMID- 28436014
TI  - A critical assessment of the synthesis and biological activity of p53/human
      double minute 2-stapled peptide inhibitors.
AB  - BACKGROUND AND PURPOSE: Helix stapling enhances the activity of peptides that
      interact with a target protein in a helical conformation. These staples are also
      supposed to change the pharmacokinetics of the molecules and promote cytoplasmic
      targeting. We assessed the extent to which the pharmacokinetic characteristics
      are a function of the staple for a peptide inhibiting the interaction of p53 with
      the human double minute 2 (Hdm2) protein and differ from those of the standard
      cationic cell-penetrating peptide nona-arginine. EXPERIMENTAL APPROACH: Stapled
      peptides and linear counterparts were synthesized in free and fluorescently
      labelled forms. Activity was determined in biochemical time-resolved Forster
      resonance energy transfer experiments and cellular high-content assays. Cellular
      uptake and intracellular trafficking were visualized by confocal microscopy. KEY
      RESULTS: Peptides showed sub-nanomolar potency. For short-time incubation, uptake
      efficiencies for the stapled and linear peptides were similar and both were taken
      up less efficiently than nona-arginine. Only for SJSA-1 cells expressing the Hdm2
      target protein, the stapled peptides showed an enhanced cytoplasmic and nuclear
      accumulation after long-term incubation. This was also observed for the linear
      counterparts, albeit to a lesser degree. For HeLa cells, which lack target
      expression, no such accumulation was observed. CONCLUSION AND IMPLICATIONS:
      Cytosolic and nuclear accumulation was not an intrinsic property of the stapled
      peptide, but resulted from capture by the target Hdm2 after endo-lysosomal
      release. Considering the rather poor uptake of stapled peptides, further
      development should focus on increasing the efficiency of uptake of these
      peptides.

PMID- 28436015
TI  - The use of topical minoxidil to accelerate nail growth: a pilot study.
AB  - Linear nail growth rate is affected by various conditions, one of which is the
      level of blood flow. Our supposition was that topical minoxidil, which has
      vasodilatory properties, can increase the rate of nail growth. The aim of this
      study was to determine the impact of topical minoxidil on nail growth. A 5%
      topical minoxidil solution was applied twice daily to the fingernails of 32
      participants. Two groups of 16 participants were randomly chosen. In one group,
      the applications were made to the right index and left ring fingernails, and, in
      the other, the left index and right ring fingernails. During each visit (weekly
      during the first month and every 2 weeks during the second month), the nail
      length of six fingernails (index, middle, and ring of both hands) was measured
      using a digital caliper. Beginning in the first week, the mean nail length of the
      treated nails was greater than that of nails in the untreated group with
      statistical significance. There were no systemic or cutaneous side effects.
      During the first month, the mean growth of the treated nails was 4.27 mm/month
      compared with 3.91 mm/month in the untreated nails (P = 0.003). These findings
      suggest that a 5% concentration of topical minoxidil can stimulate nail growth
      with increased growth beginning in the first week of application. The results may
      have important implications for the treatment of nail disorders; however, a
      comparable study involving participants with nail disorders is highly
      recommended.

PMID- 28436016
TI  - Bed bug dermatitis: detection dog as a useful survey tool for environmental
      research of Cimex lectularius.

PMID- 28436017
TI  - Attachment styles and clinical correlates in people at ultra high risk for
      psychosis.
AB  - Evidence suggests that attachment styles may influence subclinical psychosis
      phenotypes (schizotypy) and affective disorders and may play a part in the
      association between psychosis and childhood adversity. However, the role of
      attachment in the initial stages of psychosis remains poorly understood. Our main
      aim was to describe and compare attachment styles in 60 individuals at ultra high
      risk for psychosis (UHR) and a matched sample of 60 healthy volunteers (HV). The
      HV had lower anxious and avoidant attachment scores than the UHR individuals (p <
      .001). Sixty-nine percentage of the UHR group had more than one DSM-IV diagnosis,
      mainly affective and anxiety disorders. The UHR group experienced more trauma (p
      < .001) and more mood and anxiety symptoms (p < .001). Interestingly, in our UHR
      group, only schizotypy paranoia was correlated with insecure attachment. In the
      HV group, depression, anxiety, schizotypy paranoia, and social anxiety were
      correlated with insecure attachment. This difference and some discrepancies with
      previous studies involving UHR suggest that individuals at UHR may compose a
      heterogeneous group; some experience significant mood and/or anxiety symptoms
      that may not be explained by specific attachment styles. Nonetheless, measuring
      attachment in UHR individuals could help maximize therapeutic relationships to
      enhance recovery.

PMID- 28436018
TI  - Early clinical presentations and progression of calciphylaxis.
AB  - BACKGROUND: Untreated calciphylaxis is a fatal disease of intra- and
      extravascular calcification, most commonly presenting in end-stage renal disease
      (ESRD) patients. While early identification is critical for timely treatment,
      early-stage clinical and histopathological descriptions have not, to our
      knowledge, been elucidated. As early clinical recognition is essential to prompt
      definitive histopathological diagnosis, this study describes a range of clinical
      and histopathological manifestations of early-stage calciphylaxis. METHODS: Five
      patients with clinical photographs of lesions of early-phase calciphylaxis were
      chosen from a recent database of 101 patients. Their clinical histories were
      reviewed and correlated with their respective clinical and histopathological
      images of early-stage disease and progression of the disease. RESULTS: Two of the
      five patients were identified early to have calciphylaxis and were promptly
      initiated on aggressive, multimodal therapy, resulting in complete resolution and
      remission of calciphylaxis. The other three patients were also recognized in
      early stages, one without renal disease, although the disease had progressed to
      more advanced stages associated with greater morbidity and mortality.
      CONCLUSIONS: These cases demonstrate that calciphylaxis may be clinically
      misdiagnosed due to ill-defined presentations, particularly in the early stages
      without the characteristic features of livedo racemosa and ulceration. However,
      recognition in the early stages is critical to implement timely treatment. As
      such, definitively diagnostic skin biopsy should be considered early in suspected
      cases to confirm the diagnosis of calciphylaxis and ensure prompt management of
      this lethal disease.

PMID- 28436019
TI  - Antibiotic therapy for pelvic inflammatory disease.
AB  - BACKGROUND: Pelvic inflammatory disease (PID) is an infection that affects 4% to
      12% of young women, and is one of the most common causes of morbidity in this age
      group. The main intervention for acute PID is the use of broad-spectrum
      antibiotics which cover Chlamydia trachomatis, Neisseria gonorrhoeae, and
      anaerobic bacteria, administered intravenously, intramuscularly, or orally. In
      this review, we assessed the optimal treatment regimen for PID. OBJECTIVES: To
      assess the effectiveness and safety of antibiotic regimens used to treat pelvic
      inflammatory disease. SEARCH METHODS: We searched the Cochrane Sexually
      Transmitted Infections Review Group's Specialized Register, which included
      randomized controlled trials (RCTs) from 1944 to 2016, located through electronic
      searching and handsearching; the Cochrane Central Register of Controlled Trials
      (CENTRAL), Ovid platform (1991 to July 2016); MEDLINE (1946 to July 2016); Embase
      (1947 to July 2016); LILACS, iAHx interface (1982 to July 2016); World Health
      Organization International Clinical Trials Registry Platform (July 2016); Web of
      Science (2001 to July 2016); OpenGrey (1990, 1992, 1995, 1996, and 1997); and
      abstracts in selected publications. SELECTION CRITERIA: We included RCTs
      comparing the use of antibiotics with placebo or other antibiotics for the
      treatment of PID in women of reproductive age, either as inpatient or outpatient
      treatment. We limited our review to comparison of drugs in current use that are
      recommended for consideration by the 2015 US Centers for Disease Control and
      Prevention (CDC) guidelines for treatment of PID. DATA COLLECTION AND ANALYSIS:
      At least two review authors independently selected trials for inclusion,
      extracted data, and assessed risk of bias. We contacted investigators to obtain
      missing information. We resolved disagreements by consensus or by consulting a
      fourth review author if necessary. We assessed the quality of the evidence using
      GRADE criteria, classifying it as high, moderate, low, or very low. We calculated
      Mantel-Haenszel risk ratios (RR), using either random-effects or fixed-effect
      models and number needed to treat for an additional beneficial outcome or for an
      additional harmful outcome, with their 95% confidence interval (CI), to measure
      the effect of the treatments. We conducted sensitivity analyses limited to
      studies at low risk of bias, for comparisons where such studies were available.
      MAIN RESULTS: We included 37 RCTs (6348 women). The quality of the evidence
      ranged from very low to high, the main limitations being serious risk of bias
      (due to poor reporting of study methods and lack of blinding), serious
      inconsistency, and serious imprecision. Azithromycin versus doxycyclineThere was
      no clear evidence of a difference between the two drugs in rates of cure for mild
      moderate PID (RR 1.18, 95% CI 0.89 to 1.55, I2 = 72%, 2 RCTs, 243 women, very low
      quality evidence), severe PID (RR 1.00, 95% CI 0.96 to 1.05, 1 RCT, 309 women,
      low-quality evidence), or adverse effects leading to discontinuation of treatment
      (RR 0.71, 95% CI 0.38 to 1.34, 3 RCTs, 552 women, I2 = 0%, low-quality evidence).
      In a sensitivity analysis limited to a single study at low risk of bias,
      azithromycin was superior to doxycycline in achieving cure in mild-moderate PID
      (RR 1.35, 95% CI 1.10 to 1.67, 133 women, moderate-quality evidence). Quinolone
      versus cephalosporinThere was no clear evidence of a difference between the two
      drugs in rates of cure for mild-moderate PID (RR 1.04, 95% CI 0.98 to 1.10, 3
      RCTs, 459 women, I2 = 5%, low-quality evidence), severe PID (RR 1.06, 95% CI 0.91
      to 1.23, 2 RCTs, 313 women, I2 = 7%, low-quality evidence), or adverse effects
      leading to discontinuation of treatment (RR 2.24, 95% CI 0.52 to 9.72, 5 RCTs,
      772 women, I2 = 0%, very low-quality evidence). Nitroimidazole versus no use of
      nitroimidazoleThere was no conclusive evidence of a difference between the
      nitroimidazoles (metronidazole) group and the group receiving other drugs with
      activity over anaerobes (e.g. amoxicillin-clavulanate) in rates of cure for mild
      moderate PID (RR 1.01, 95% CI 0.93 to 1.10, 5 RCTs, 2427 women, I2 = 60%,
      moderate-quality evidence), severe PID (RR 0.96, 95% CI 0.92 to 1.01, 11 RCTs,
      1383 women, I2 = 0%, moderate-quality evidence), or adverse effects leading to
      discontinuation of treatment (RR 1.00, 95% CI 0.63 to 1.59; participants = 3788;
      studies = 16; I2 = 0% , low-quality evidence). In a sensitivity analysis limited
      to studies at low risk of bias, findings did not differ substantially from the
      main analysis (RR 1.06, 95% CI 0.98 to 1.15, 2 RCTs, 1201 women, I2 = 32%, high
      quality evidence). Clindamycin plus aminoglycoside versus quinoloneThere was no
      evidence of a difference between the two groups in rates of cure for mild
      moderate PID (RR 0.88, 95% CI 0.69 to 1.13, 1 RCT, 25 women, very low-quality
      evidence), severe PID (RR 1.02, 95% CI 0.87 to 1.19, 2 studies, 151 women, I2 =
      0%, low-quality evidence), or adverse effects leading to discontinuation of
      treatment (RR 0.21, 95% CI 0.02 to 1.72, 3 RCTs, 163 women, very low-quality
      evidence). Clindamycin plus aminoglycoside versus cephalosporinThere was no clear
      evidence of a difference between the two groups in rates of cure for mild
      moderate PID (RR 1.02, 95% CI 0.95 to 1.09, 2 RCTs, 150 women, I2 = 0%, low
      quality evidence), severe PID (RR 1.00, 95% CI 0.95 to 1.06, 10 RCTs, 959 women,
      I2 = 21%, moderate-quality evidence), or adverse effects leading to
      discontinuation of treatment (RR 0.78, 95% CI 0.18 to 3.42, 10 RCTs, 1172 women,
      I2 = 0%, very low-quality evidence). AUTHORS' CONCLUSIONS: We found no conclusive
      evidence that one regimen of antibiotics was safer or more effective than any
      other for the cure of PID, and there was no clear evidence for the use of
      nitroimidazoles (metronidazole) compared to use of other drugs with activity over
      anaerobes. Moderate-quality evidence from a single study at low risk of bias
      suggested that a macrolide (azithromycin) may be more effective than a
      tetracycline (doxycycline) for curing mild-moderate PID. Our review considered
      only the drugs that are currently used and mentioned by the CDC.

PMID- 28436020
TI  - The Common Sense of Considering the Senses in Patient Communication.

PMID- 28436021
TI  - Burning mouth syndrome: results of screening tests for vitamin and mineral
      deficiencies, thyroid hormone, and glucose levels-experience at Mayo Clinic over
      a decade.
AB  - BACKGROUND: Burning mouth syndrome (BMS) is a disorder characterized by chronic
      mouth pain in the absence of objective clinical abnormalities. Vitamin or mineral
      deficiencies may have a role in BMS, but data regarding the prevalence and
      relevance of hematinic deficiencies are conflicting. We aimed to determine the
      frequency of specific laboratory abnormalities in patients with BMS. METHODS: We
      retrospectively reviewed the results of screening blood tests in patients with
      BMS at our institution between January 2003 and December 2013. RESULTS: Among 659
      patients with BMS, the most common decreased values or deficiencies were vitamin
      D3 (15%), vitamin B2 (15%), vitamin B6 (5.7%), zinc (5.7%), vitamin B1 (5.3%),
      thyrotropin (TSH) (3.2%), vitamin B12 (0.8%), and folic acid (0.7%). Laboratory
      values for fasting blood glucose and TSH were increased in 23.7% and 5.2%,
      respectively. CONCLUSIONS: In patients with symptoms of BMS, our results suggest
      it is reasonable to screen for fasting blood glucose, vitamin D (D2 and D3 ),
      vitamin B6 , zinc, vitamin B1 , and TSH. Deficiencies of vitamin B12 and folic
      acid were rare (<1% abnormal).

PMID- 28436022
TI  - Ventilation via the 2.4 mm internal diameter Tritube(r) with cuff - new
      possibilities in airway management.
AB  - BACKGROUND: A small tube may facilitate tracheal intubation and improve surgical
      access. We describe our initial experience with the Tritube(r) that is a novel
      cuffed endotracheal tube with a 2.4 mm internal diameter. METHODS: The Tritube(r)
      was used in seven adult Ear-Nose-and Throat surgical patients with airway
      narrowing or whose surgical access was facilitated by this small-bore
      endotracheal tube. Ventilation through Tritube(r) is performed with the manually
      operated Ventrain(r) -ventilator that allows active suctioning during expiration,
      therefore facilitating normoventilation through small diameter airways. RESULTS:
      The small diameter of Tritube(r) seemed to improve glottis visualisation during
      intubations and gave excellent working conditions for surgery. Two patients were
      intubated awake with a flexible scope and a guide wire or with an angulated video
      laryngoscope. One patient had almost complete glottic occlusion that just allowed
      for passage of the Tritube(r) . Adequate ventilation was achieved in all patients
      and intratracheal pressure was kept between 5 and 20 cm H2 O. The tube was well
      tolerated after emergence from anaesthesia and kept intratracheally in five awake
      patients in the post-operative recovery unit, in one case for more than 1 h.
      Ventilating with Ventrain(r) through Tritube(r) demands meticulous breath by
      breath measurement and adjustment of the intratracheal pressure. CONCLUSION: The
      2.4 mm internal diameter Tritube(r) seems to facilitate tracheal intubation and
      to provide unprecedented view of the intubated airway during oral, pharyngeal,
      laryngeal or tracheal procedures in adults. This technique has the potential to
      replace temporary tracheostomy, jet-ventilation or extra-corporal membrane
      oxygenation in selected patients.

PMID- 28436024
TI  - Hair diameter evaluation in different regions of the safe donor area in Asian
      populations.
AB  - BACKGROUND: There is little information about how hair diameter differences
      within the safe donor area. Thicker or thinner hair may be needed depending on
      the recipient area, hairline design, and surgical purpose. METHODS: Thirty-eight
      non-alopecic subjects (19 males and 19 females) were evaluated. The safe donor
      area was defined as the area contained within 28 cm from the horizontal plane of
      the upper border of the hair rim to the vertical line of the bilateral external
      acoustic meatus. Seven zones were defined starting 2 cm on each side (bilateral 4
      cm) from the mid-occiput to the temporal side. The diameters of 10 randomly
      selected anagen hairs were measured from each of the seven zones. RESULTS: The
      results showed significant differences in hair diameter by zone between males and
      females (P < 0.0001). In general, hair diameter tended to decrease from zone 3 to
      7. CONCLUSION: Our results suggest that safe donor areas between zones 4 and 7
      could be useful for specific hair transplantation surgeries requiring thinner
      hair, such as eyebrows, eyelashes, and female hairline correction surgery,
      whereas hair from zones 1-3 could be more useful for those requiring thicker
      hair, such as male and female pattern hair loss. Our data could be clinically
      valuable for planning hair transplant surgery and choosing the most optimal donor
      region.

PMID- 28436025
TI  - Melanoma in situ of lentigo maligna type in a young woman.

PMID- 28436023
TI  - Activation of AMP-activated protein kinase by metformin ablates angiotensin II
      induced endoplasmic reticulum stress and hypertension in mice in vivo.
AB  - BACKGROUND AND PURPOSE: Metformin, one of the most frequently prescribed
      medications for type 2 diabetes, reportedly exerts BP-lowering effects in
      patients with diabetes. However, the effects and underlying mechanisms of
      metformin on BP in non-diabetic conditions remain to be determined. The aim of
      the present study was to determine the effects of metformin on angiotensin II
      (Ang II) infusion-induced hypertension in vivo. EXPERIMENTAL APPROACH: The
      effects of metformin on BP were investigated in wild-type (WT) C57BL/6J mice and
      in mice lacking AMP-activated protein kinase alpha2 (AMPKalpha2) mice with or
      without Ang II infusion. Also, the effect of metformin on Ang II-induced
      endoplasmic reticulum (ER) stress was explored in cultured human vascular smooth
      muscle cells (hVSMCs). KEY RESULTS: Metformin markedly reduced BP in Ang II
      infused WT mice but not in AMPKalpha2-deficient mice. In cultured hVSMCs, Ang II
      treatment resulted in inactivation of AMPK, as well as the subsequent induction
      of spliced X-box binding protein-1, phosphorylation of eukaryotic translation
      initiation factor 2alpha and expression of glucose-regulated protein 78 kDa,
      representing three well-characterized ER stress biomarkers. Moreover, AMPK
      activation by metformin ablated Ang II-induced ER stress in hVSMCs.
      Mechanistically, metformin-activated AMPKalpha2 suppressed ER stress by
      increasing phospholamban phosphorylation. CONCLUSION AND IMPLICATIONS: Metformin
      alleviates Ang II-triggered hypertension in mice by activating AMPKalpha2, which
      mediates phospholamban phosphorylation and inhibits Ang II-induced ER stress in
      vascular smooth muscle cells.

PMID- 28436026
TI  - Studies of Physician-Patient Communication with Older Patients: How Often is
      Hearing Loss Considered? A Systematic Literature Review.
AB  - Hearing loss is remarkably prevalent in the geriatric population: one-quarter of
      adults aged 60-69 and 80% of adults aged 80 years and older have bilateral
      disabling loss. Only about one in five adults with hearing loss wears a hearing
      aid, leaving many vulnerable to poor communication with healthcare providers. We
      quantified the extent to which hearing loss is mentioned in studies of physician
      patient communication with older patients, and the degree to which hearing loss
      is incorporated into analyses and findings. We conducted a structured literature
      search within PubMed for original studies of physician-patient communication with
      older patients that were published since 2000, using the natural language phrase
      "older patient physician communication." We identified 409 papers in the initial
      search, and included 67 in this systematic review. Of the 67 papers, only 16
      studies (23.9%) included any mention of hearing loss. In six of the 16 studies,
      hearing loss was mentioned only; in four studies, hearing loss was used as an
      exclusion criterion; and in two studies, the extent of hearing loss was measured
      and reported for the sample, with no further analysis. Three studies examined or
      reported on an association between hearing loss and the quality of physician
      patient communication. One study included an intervention to temporarily mitigate
      hearing loss to improve communication. Less than one-quarter of studies of
      physician-elderly patient communication even mention that hearing loss may affect
      communication. Methodologically, this means that many studies may have omitted an
      important potential confounder. Perhaps more importantly, research in this field
      has largely overlooked a highly prevalent, important, and remediable influence on
      the quality of communication.

PMID- 28436027
TI  - Production and characterization of active recombinant human factor II with
      consistent sialylation.
AB  - Coagulation factor II (prothrombin; FII) is the pre-proteolyzed precursor to
      thrombin in the coagulation cascade. It has 10 sites of gamma-carboxylation,
      which are required for its bioactivity, and is N-glycosylated at three of four
      putative sites. Production of recombinant human FII (rhFII) using a platform fed
      batch process designed for monoclonal antibody production resulted in low levels
      of gamma-carboxylation and sialylation. There have not been any prior reports of
      successful process development and clinical manufacture of rhFII with optimal,
      consistent gamma-carboxylation and sialylation. In order to develop such a fed
      batch process, various process parameters were evaluated to determine their
      impact on product quality. Process temperature and temperature shift timing were
      important for both sialic acid level and gamma-carboxyglutamate (Gla) level. In
      addition, vitamin K concentration and the type of surfactant used for preparation
      of vitamin K stock solution were also important for gamma carboxylation. A fed
      batch study performed with various medium additives known to be involved in the N
      glycosylation pathway, such as N-acetyl-d-mannosamine (ManNAc), galactose (Gal),
      dexamethasone, and manganese sulfate, increased the level of sialylation and
      enabled the elucidation of some potential bottlenecks in the sialylation pathway.
      The optimized process based on these studies yielded a reduction in the level of
      missing Gla by 0.4 moles per mole of rhFII in cell culture and a nearly threefold
      increase in sialic acid level. The process was successfully implemented at the
      2000 L scale where a high Gla level and sialylation levels were achieved in all
      GMP lots. Biotechnol. Bioeng. 2017;114: 1991-2000. (c) 2017 Wiley Periodicals,
      Inc.

PMID- 28436028
TI  - Chronic bullous disease of childhood with IgG reactivity to p200 antigen.

PMID- 28436030
TI  - Tracking the behavior of Maillard browning in lysine/arginine-sugar model systems
      under high hydrostatic pressure.
AB  - BACKGROUND: High-pressure processing is gaining popularity in the food industry.
      However, its effect on the Maillard reaction during high-pressure-assisted
      pasteurization and sterilization is not well documented. This study aimed to
      investigate the effects of high hydrostatic pressure on the Maillard reaction
      during these processes using amino acid (lysine or arginine)-sugar (glucose or
      fructose) solution models. RESULTS: High pressure retarded the intermediate and
      final stages of the Maillard reaction in the lysine-sugar model. For the lysine
      glucose model, the degradation rate of Amadori compounds was decelerated, while
      acceleration was observed in the arginine-sugar model. Increased temperature not
      only accelerated the Maillard reaction over time but also formed fluorescent
      compounds with different emission wavelengths. Lysine reacted with the sugars
      more readily than arginine under the same conditions. In addition, it was easier
      for lysine to react with glucose, whereas arginine reacted more readily with
      fructose under high pressure. CONCLUSION: High pressure exerts different effects
      on lysine-sugar and arginine-sugar models. (c) 2017 Society of Chemical Industry.

PMID- 28436029
TI  - WNT4 acts downstream of BMP2 to mediate the regulation of ATRA signaling on RUNX1
      expression: Implications for terminal differentiation of antler chondrocytes.
AB  - Although ATRA is involved in regulating the proliferation and differentiation of
      chondrocytes, its underlying mechanism remains unknown. Here we showed that ATRA
      could stimulate the proliferation of antler chondrocytes and expression of COL X
      and MMP13 which were two well-known markers for hypertrophic chondrocytes.
      Silencing of CRABP2 prevented the induction of ATRA on chondrocyte terminal
      differentiation, while overexpression of CRABP2 exhibited the opposite effects.
      CYP26A1 and CYP26B1 weakened the sensitivity of antler chondrocytes to ATRA.
      Further analysis evidenced that ATRA might induce chondrocyte terminal
      differentiation and modulate the expression of BMP2, WNT4, and RUNX1 through
      RARalpha/RXRalpha. Knockdown of BMP2 enhanced the induction of ATRA on the
      expression of COL X and MMP13, whereas overexpression of BMP2 abrogated this
      effectiveness. WNT4 might mediate the effects of ATRA and BMP2 on chondrocyte
      terminal differentiation. Dysregulation of BMP2 impaired the regulation of ATRA
      on WNT4 expression. Administration of ATRA to antler chondrocytes transfected
      with RUNX1 siRNA failed to induce the differentiation. Conversely, rRUNX1
      strengthened the stimulation of ATRA on the expression of COL X and MMP13.
      Simultaneously, RUNX1 was a downstream effector of BMP2 and WNT4 in chondrocyte
      terminal differentiation. Moreover, WNT4 might play an important role in the
      crosstalk between BMP2 and RUNX1. Attenuation of BMP2 or WNT4 enhanced the
      interaction between ATRA and RUNX1, while constitutive expression of BMP2 or WNT4
      reversed the regulation of ATRA on RUNX1. Collectively, WNT4 may act downstream
      of BMP2 to mediate the effects of ATRA on the terminal differentiation of antler
      chondrocytes through targeting RUNX1.

PMID- 28436031
TI  - Quantification of Methamphetamine in Mouse Thighbones Buried in Soil.
AB  - Bone samples are used for analysis of drugs in decomposed or skeletonized bodies.
      Toxicological analyses of buried bones are important for determining the causes
      and circumstances of death. In this study, methamphetamine and amphetamine
      concentrations in heart blood, thigh muscles, and thighbones were analyzed using
      solid-phase extraction with liquid chromatography-tandem mass spectrometry.
      Methamphetamine concentrations in heart blood, thigh muscle, and thighbone ranged
      from 0.041 to 0.873 MUg/mL, 0.649 to 2.623 MUg/g, and 56.543 to 643.371 MUg/g,
      respectively. Thighbone concentrations were significantly higher than those in
      heart blood or thigh muscles were. Methamphetamine concentrations in buried
      thighbone (4.010-45.785 MUg/g) were significantly lower than those of unburied
      thighbones were (56.543-643.371 MUg/g). Methamphetamine and amphetamine were
      detected in thighbones buried for 7-180 days. These findings indicate that the
      methamphetamine concentrations in bone are higher and decrease after burial in
      soil.

PMID- 28436032
TI  - Application of MALDI-TOF MS for Estimating the Postmortem Interval in Rat Muscle
      Samples.
AB  - Estimating the postmortem interval (PMI) is very important in the forensic
      sciences. Although many approaches have been used for estimating the PMI,
      accurate PMI calculations are still difficult. In this study, four Sprague Dawley
      (SD) rats were sacrificed by suffocation, and muscle samples were collected by
      dissection at various time intervals (0, 48, 96, and 144 h) after death. All
      samples were probed using matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOFMS) to obtain molecular images and data for
      principal component analysis (PCA). The results showed that the peaks at m/z
      1511, 1543, 1564, 1586 clearly decreased in intensity from 0 to 144 h postmortem
      and that the time groups were separated from each other on the PCA score plot.
      The prediction model showed high recognition capability (95.93%) and cross
      validation (83.72%). Our work suggests that MALDI-TOF MS can be used to determine
      the PMI.

PMID- 28436033
TI  - Assessing Impact Direction in 3-point Bending of Human Femora: Incomplete
      Butterfly Fractures and Fracture Surfaces,.
AB  - Current literature associates bending failure with butterfly fracture, in which
      fracture initiates transversely at the tensile surface of a bent bone and
      branches as it propagates toward the impact surface. The orientation of the
      resulting wedge fragment is often considered diagnostic of impact direction.
      However, experimental studies indicate bending does not always produce complete
      butterfly fractures or produces wedge fragments variably in tension or
      compression, precluding their use in interpreting directionality. This study
      reports results of experimental 3-point bending tests on thirteen unembalmed
      human femora. Complete fracture patterns varied following bending failure, but
      incomplete fractures and fracture surface characteristics were observed in all
      impacted specimens. A flat, billowy fracture surface was observed in tension,
      while jagged, angular peaks were observed in compression. Impact direction was
      accurately reconstructed using incomplete tension wedge butterfly fractures and
      tension and compression fracture surface criteria in all thirteen specimens.

PMID- 28436034
TI  - Celluclast 1.5L pretreatment enhanced aroma of palm kernels and oil after kernel
      roasting.
AB  - BACKGROUND: The aroma of palm kernel oil (PKO) affects its applications. Little
      information is available on how enzymatic modification of palm kernels (PK)
      affects PK and PKO aroma after kernel roasting. RESULTS: Celluclast (cellulase)
      pretreatment of PK resulted in a 2.4-fold increment in the concentration of
      soluble sugars, with glucose being increased by 6.0-fold. Higher levels of 1.7-,
      1.8- and 1.9-fold of O-heterocyclic volatile compounds were found in the treated
      PK after roasting at 180  degrees C for 8, 14 and 20 min respectively relative to
      the corresponding control, with furfural, 5-methyl-2-furancarboxaldehyde, 2
      furanmethanol and maltol in particularly higher amounts. Volatile differences
      between PKOs from control and treated PK were also found, though less obvious
      owing to the aqueous extraction process. Principal component analysis based on
      aroma-active compounds revealed that upon the proceeding of roasting, the
      differentiation between control and treated PK was enlarged while that of
      corresponding PKOs was less clear-cut. Celluclast pretreatment enabled the medium
      roasted PK to impart more nutty, roasty and caramelic odor and the corresponding
      PKO to impart more caramelic but less roasty and burnt notes. CONCLUSION:
      Celluclast pretreatment of PK followed by roasting may be a promising new way of
      improving PKO aroma. (c) 2017 Society of Chemical Industry.

PMID- 28436035
TI  - NAP counteracts hyperglycemia/hypoxia induced retinal pigment epithelial barrier
      breakdown through modulation of HIFs and VEGF expression.
AB  - Diabetic macular edema (DME) is a common complication leading to a central vision
      loss in patients with diabetes. In this eye pathology, the hyperglycaemic/hypoxic
      microenvironment of pigmented epithelium is responsible for outer blood retinal
      barrier integrity changes. More recently, we have shown that a small peptide
      derived from the activity-dependent neuroprotective protein (ADNP), known as NAP,
      counteracts damages occurring during progression of diabetic retinopathy by
      modulating HIFs/VEGF pathway. Here, we have investigated for the first time the
      role of this peptide on outer blood retinal barrier (BRB) integrity exposed to
      hyperglycaemic/hypoxic insult mimicking a model in vitro of DME. To characterize
      NAP role on disease's pathogenesis, we have analyzed its effect on HIFs/VEGF
      system in human retinal pigmented epithelial cells, ARPE-19, grown in high
      glucose and low oxygen tension. The results have shown that NAP prevents outer
      BRB breakdown by reducing HIF1alpha/HIF2alpha, VEGF/VEGFRs, and increasing
      HIF3alpha expression, moreover it is able to reduce the percentage of apoptotic
      cells by modulating the expression of two death related genes, BAX and Bcl2.
      Further investigations are needed to determine the possible use of NAP in DME
      treatment.

PMID- 28436036
TI  - Oxidative behavior of (+)-catechin in the presence of inactive dry yeasts: a
      comparison with sulfur dioxide, ascorbic acid and glutathione.
AB  - BACKGROUND: The antioxidant capacity of an inactive dry yeast preparation (YD)
      was investigated by conventional analytical methods (spectrophotometry, high
      performance liquid chromatography) as well as by cyclic voltammetry in a (+)
      catechin model wine and compared with that of some of the most common
      antioxidants found in wine: sulfur dioxide, ascorbic acid and glutathione.
      RESULTS: Sulfur dioxide was the highest-performing substance in protecting (+)
      catechin against browning, followed by ascorbic acid and the YD preparation.
      Sulfites were the only antioxidant whose activity was clearly detectable in the
      model wines after 29 days of storage. Voltammetric studies demonstrated that the
      antioxidant capacity of the products tested was connected to their intrinsic
      characteristics and their molar concentrations (catechin/antioxidant molar
      ratio). CONCLUSION: The YD preparation displayed a certain ability to protect
      polyphenols against browning. The antioxidant activity of YDs towards (+)
      catechin appeared to be based on different mechanisms with respect to that of the
      other products tested: the insoluble portion of these preparations (cell wall
      residues) might have a non-negligible role, even if the ability of YDs to release
      compounds able to suppress oxidation cannot be rejected. Direct comparison of the
      different antioxidants led to interesting indications concerning their mechanism
      of action in wine-like solution, depending on their concentration and intrinsic
      characteristics. (c) 2017 Society of Chemical Industry.

PMID- 28436037
TI  - High-level Ab Initio Absorption Spectra Simulations of Neutral, Anionic and
      Neutral+ Chromophore of Green Fluorescence Protein Chromophore Models in Gas
      Phase and Solution.
AB  - Semiclassical ab initio simulations of the absorption spectra of neutral and
      anionic p-hydroxybenzylidene-2,3-dimethylimidazolinone (p-HBDI), a model
      chromophore of green fluorescent protein (GFP) and of a positively charged
      neutral (N+)-HBDI chromophore model, were performed in gas phase with the
      resolution-of-identity algebraic diagrammatic construction through second-order
      (RI-ADC(2)) method. The calculated absorption spectra in gas phase are composed
      of one band centered at 3.51 eV (HBDI), 2.50 eV (HBDI- ) and 3.02 eV ((N+)-HBDI)
      owing to the absorption of the first 1 pipi* transition. Band maxima are
      redshifted by ~0.1 eV with respect to the corresponding vertical energies. The
      COSMO-RI-ADC(2) calculations of the first vertical excitation energy of HBDI,
      HBDI- and (N+)-HBDI forms in polar solution including microsolvation simulate the
      observed solvent redshift for neutral HBDI and the solvent blueshift of the HBDI-
      and (N+)-HBDI forms. The state-specific solvation approach applied to TDDFT
      calculations reproduced the experimental solvent shifts for the three HBDI forms,
      demonstrating a more accurate theoretical description as compared to the linear
      response TDDFT approach.

PMID- 28436038
TI  - Direct current stimulation boosts synaptic gain and cooperativity in vitro.
AB  - KEY POINTS: Direct current stimulation (DCS) polarity specifically modulates
      synaptic efficacy during a continuous train of presynaptic inputs, despite
      synaptic depression. DCS polarizes afferent axons and postsynaptic neurons,
      boosting cooperativity between synaptic inputs. Polarization of afferent neurons
      in upstream brain regions may modulate activity in the target brain region during
      transcranial DCS (tDCS). A statistical theory of coincident activity predicts
      that the diffuse and weak profile of current flow can be advantageous in
      enhancing connectivity between co-active brain regions. ABSTRACT: Transcranial
      direct current stimulation (tDCS) produces sustained and diffuse current flow in
      the brain with effects that are state dependent and outlast stimulation. A
      mechanistic explanation for tDCS should capture these spatiotemporal features. It
      remains unclear how sustained DCS affects ongoing synaptic dynamics and how
      modulation of afferent inputs by diffuse stimulation changes synaptic activity at
      the target brain region. We tested the effect of acute DCS (10-20 V m-1 for 3-5
      s) on synaptic dynamics with constant rate (5-40 Hz) and Poisson-distributed (4
      Hz mean) trains of presynaptic inputs. Across tested frequencies, sustained
      synaptic activity was modulated by DCS with polarity-specific effects. Synaptic
      depression attenuates the sensitivity to DCS from 1.1% per V m-1 to 0.55%. DCS
      applied during synaptic activity facilitates cumulative neuromodulation,
      potentially reversing endogenous synaptic depression. We establish these effects
      are mediated by both postsynaptic membrane polarization and afferent axon fibre
      polarization, which boosts cooperativity between synaptic inputs. This
      potentially extends the locus of neuromodulation from the nominal target to
      afferent brain regions. Based on these results we hypothesized the polarization
      of afferent neurons in upstream brain regions may modulate activity in the target
      brain region during tDCS. A multiscale model of transcranial electrical
      stimulation including a finite element model of brain current flow, numerical
      simulations of neuronal activity, and a statistical theory of coincident activity
      predicts that the diffuse and weak profile of current flow can be advantageous.
      Thus, we propose that specifically because tDCS is diffuse, weak and sustained it
      can boost connectivity between co-active brain regions.

PMID- 28436039
TI  - Nutrient retention values and cooking yield factors for three South African lamb
      and mutton cuts.
AB  - BACKGROUND: Nutrient content of raw and cooked foods is important for formulation
      of healthy diets. The retention of nutrients during cooking can be influenced by
      various factors, including animal age, carcass characteristics and cooking
      method, and these factors are often unique to specific countries. Here the
      effects of animal age (lamb and mutton) and carcass cut (shoulder, loin and leg)
      combined with cooking method (moist heat and dry heat) on yield and nutrient
      retention of selected nutrients of South African sheep carcasses were studied.
      RESULTS: Cooking yields and moisture retention were lower for lamb loin but
      higher for lamb leg. Energy and fat retention were higher for all cuts of mutton
      compared with lamb, while higher retention values for cholesterol were recorded
      for lamb. Mutton retained more iron (P = 0.10) and zinc and also more vitamin B2
      , B6 and B12 than lamb. Shoulder cooked according to moist heat cooking method
      retained more magnesium, potassium and sodium. CONCLUSION: Incorporating these
      retention and yield values into the South African Medical Research Council's Food
      Composition Tables provides a reliable reference to all concerned with nutrient
      content of food. It will also guide practitioners and primary industry to adjust
      animal production aimed at optimum nutrient content to specific diets. (c) 2017
      Society of Chemical Industry.

PMID- 28436040
TI  - Synergistic use of biochar, compost and plant growth-promoting rhizobacteria for
      enhancing cucumber growth under water deficit conditions.
AB  - BACKGROUND: Limited information is available about the effectiveness of biochar
      with plant growth-promoting rhizobacteria (PGPR) and compost. A greenhouse study
      was conducted to evaluate the effect of biochar in combination with compost and
      PGPR (Pseudomonas fluorescens) for alleviating water deficit stress. Both
      inoculated and un-inoculated cucumber seeds were sown in soil treated with
      biochar, compost and biochar + compost. Three water levels - field capacity (D0),
      75% field capacity (D1) and 50% field capacity (D2) - were maintained. RESULTS:
      The results showed that water deficit stress significantly suppressed the growth
      of cucumber; however, synergistic use of biochar, compost and PGPR mitigated the
      negative impact of stress. At D2, the synergistic use of biochar, compost and
      PGPR caused significant increases in shoot length, shoot biomass, root length and
      root biomass, which were respectively 88, 77, 89 and 74% more than in the un
      inoculated control. Significant improvements in chlorophyll and relative water
      contents as well as reduction in leaf electrolyte leakage demonstrated the
      effectiveness of this approach. Moreover, the highest population of P.
      fluorescens was observed where biochar and compost were applied together.
      CONCLUSION: These results suggest that application of biochar with PGPR and/or
      compost could be an effective strategy for enhancing plant growth under stress.
      (c) 2017 Society of Chemical Industry.

PMID- 28436041
TI  - CD117 immunohistochemistry in sarcomatoid porocarcinoma.

PMID- 28436042
TI  - Are p-values under attack? Contribution to the discussion of 'A critical
      evaluation of the current "p-value controversy" '.

PMID- 28436043
TI  - European Society of Endodontology position statement: the use of antibiotics in
      endodontics.
AB  - This position statement represents a consensus of an expert committee convened by
      the European Society of Endodontology (ESE) on Antibiotics in Endodontics. The
      statement is based on current scientific evidence as well as the expertise of the
      committee. The goal is to provide dentists and other healthcare workers with
      evidence-based criteria for when to use antibiotics in the treatment of
      endodontic infections, traumatic injuries of the teeth, revascularization
      procedures in immature teeth with pulp necrosis, and in prophylaxis for medically
      compromised patients. It also highlights the role that dentists and others can
      play in preventing the overuse of antibiotics. A recent review article provides
      the basis for this position statement and more detailed background information
      (International Endodontic Journal, 2017, https://doi.org/10.1111/iej.12741).
      Given the dynamic nature of research in this area, this position statement will
      be updated at appropriate intervals.

PMID- 28436044
TI  - Structure, bioactivity, and synthesis of methylated flavonoids.
AB  - Methylated flavonoids are an important type of natural flavonoid derivative with
      potentially multiple health benefits; among other things, they have improved
      bioavailability compared with flavonoid precursors. Flavonoids have been
      documented to have broad bioactivities, such as anticancer, immunomodulation, and
      antioxidant activities, that can be elevated, to a certain extent, by
      methylation. Understanding the structure, bioactivity, and bioavailability of
      methylated flavonoids, therefore, is an interesting topic with broad potential
      applications. Though methylated flavonoids are widely present in plants, their
      levels are usually low. Because developing efficient techniques to produce these
      chemicals would likely be beneficial, we provide an overview of their chemical
      and biological synthesis.

PMID- 28436045
TI  - Improved methods for the marginal analysis of longitudinal data in the presence
      of time-dependent covariates.
AB  - Generalized estimating equations (GEEs) are commonly used for the marginal
      analysis of longitudinal data. In order to obtain consistent regression parameter
      estimates, these estimating equations must be unbiased. However, in the presence
      of certain types of time-dependent covariates, these equations can be biased
      unless they incorporate the independence working correlation structure. Moreover,
      in this case, regression parameter estimation can be very inefficient because not
      all valid moment conditions are incorporated within the corresponding estimating
      equations. Therefore, approaches based on the generalized method of moments or
      quadratic inference functions have been proposed in order to utilize all valid
      moment conditions. However, we have found in previous studies, as well as the
      current study, that such methods will not always provide valid inference and can
      also be improved upon in terms of finite-sample regression parameter estimation.
      Therefore, we propose both a modified GEE approach and a method selection
      strategy in order to ensure valid inference with the goal of improving regression
      parameter estimation. In a simulation study and application example, we compare
      existing and proposed methods and demonstrate that our modified GEE approach
      performs well, and the correlation information criterion has good accuracy with
      respect to selecting the best approach in terms of regression parameter
      estimation. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28436046
TI  - Simulation-based adjustment after exploratory biomarker subgroup selection in
      phase II.
AB  - As part of the evaluation of phase II trials, it is common practice to perform
      exploratory subgroup analyses with the aim of identifying patient populations
      with a beneficial treatment effect. When investigating targeted therapies, these
      subgroups are typically defined by biomarkers. Promising results may lead to the
      decision to select the respective subgroup as the target population for a
      subsequent phase III trial. However, a selection based on a large observed
      treatment effect may potentially induce an upwards-bias leading to over
      optimistic expectations on the success probability of the phase III trial. We
      describe how Approximate Bayesian Computation techniques can be used to derive a
      simulation-based bias adjustment method in this situation. Recommendations for
      the implementation of the approach are given. Simulation studies show that the
      proposed method reduces bias substantially compared with the maximum likelihood
      estimator. The procedure is illustrated with data from an oncology trial.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28436047
TI  - Propensity scores based methods for estimating average treatment effect and
      average treatment effect among treated: A comparative study.
AB  - Propensity score based statistical methods, such as matching, regression,
      stratification, inverse probability weighting (IPW), and doubly robust (DR)
      estimating equations, have become popular in estimating average treatment effect
      (ATE) and average treatment effect among treated (ATT) in observational studies.
      Propensity score is the conditional probability receiving a treatment assignment
      with given covariates, and propensity score is usually estimated by logistic
      regression. However, a misspecification of the propensity score model may result
      in biased estimates for ATT and ATE. As an alternative, the generalized boosting
      method (GBM) has been proposed to estimate the propensity score. GBM uses
      regression trees as weak predictors and captures nonlinear and interactive
      effects of the covariate. For GBM-based propensity score, only IPW methods have
      been investigated in the literature. In this article, we provide a comparative
      study of the commonly used propensity score based methods for estimating ATT and
      ATE, and examine their performances when propensity score is estimated by
      logistic regression and GBM, respectively. Extensive simulation results indicate
      that the estimators for ATE and ATT may vary greatly due to different methods. We
      concluded that (i) regression may not be suitable for estimating ATE and ATT
      regardless of the estimation method of propensity score; (ii) IPW and
      stratification usually provide reliable estimates of ATT when propensity score
      model is correctly specified; (iii) the estimators of ATE based on
      stratification, IPW, and DR are close to the underlying true value of ATE when
      propensity score is correctly specified by logistic regression or estimated using
      GBM.

PMID- 28436048
TI  - Dealing with the tension: how residents seek autonomy and participation in the
      workplace.
AB  - CONTEXT: The workplace can be a strenuous setting for residents: although it
      offers a wealth of learning opportunities, residents find themselves juggling
      their responsibilities. Even though supervisors regulate what is afforded to
      residents, the former find it difficult to strike the proper balance between
      residents' independence and support, which could create tensions. But what
      tensions do residents experience during clinical supervision and how do they cope
      with them to maximise their learning opportunities? Understanding how residents
      act on different affordances in the workplace is of paramount importance, as it
      influences their learning. METHOD: Residents from different levels of training
      and disciplines participated in three focus groups (n = 19) and 10 semi
      structured interviews (n = 10). The authors recruited these trainees using
      purposive and convenience sampling. Audio-recordings were transcribed verbatim
      and the ensuing scripts were analysed using a constructivist grounded theory
      methodology. RESULTS: Residents reported that the autonomy and practice
      opportunities given by their supervisors were either excessive or too limited,
      and both were perceived as tensions. When in excess, trainees enlisted the help
      of their supervisor or peers, depending on how safe they recognised the learning
      environment to be. When practice opportunities were curtailed, trainees tried to
      negotiate more if they felt the learning environment was safe. When they did not,
      trainees became passive observers. Learning from each engagement was subject to
      the extent of intersubjectivity achieved between the actors involved.
      CONCLUSIONS: Tensions arose when supervisors did not give trainees the desired
      degree of autonomy and opportunities to participate. Trainees responded in
      various ways to maximise their learning opportunities. For these different
      engagement-related responses to enhance workplace learning in specialty training,
      achieving intersubjectivity between trainee and supervisor seems foundational.

PMID- 28436049
TI  - Elevated carbon dioxide reduces emission of herbivore-induced volatiles in Zea
      mays.
AB  - Terpene volatiles produced by sweet corn (Zea mays) upon infestation with pests
      such as beet armyworm (Spodoptera exigua) function as part of an indirect defence
      mechanism by attracting parasitoid wasps; yet little is known about the impact of
      climate change on this form of plant defence. To investigate how a central
      component of climate change affects indirect defence, we measured herbivore
      induced volatile emissions in plants grown under elevated carbon dioxide (CO2 ).
      We found that S. exigua infested or elicitor-treated Z. mays grown at elevated
      CO2 had decreased emission of its major sesquiterpene, (E)-beta-caryophyllene and
      two homoterpenes, (3E)-4,8-dimethyl-1,3,7-nonatriene and (3E,7E)-4,8,12-trimethyl
      1,3,7,11-tridecatetraene. In contrast, inside the leaves, elicitor-induced (E)
      beta-caryophyllene hyper-accumulated at elevated CO2 , while levels of
      homoterpenes were unaffected. Furthermore, gene expression analysis revealed that
      the induction of terpene synthase genes following treatment was lower in plants
      grown at elevated CO2 . Our data indicate that elevated CO2 leads both to a
      repression of volatile synthesis at the transcriptional level and to limitation
      of volatile release through effects of CO2 on stomatal conductance. These
      findings suggest that elevated CO2 may alter the ability of Z. mays to utilize
      volatile terpenes to mediate indirect defenses.

PMID- 28436050
TI  - Comparing performance of surgeons using risk-adjusted procedures.
AB  - It is naive and incorrect to use the proportions of successful operations to
      compare the performance of surgeons because the patients' risk profiles are
      different. In this paper, we explore the use of risk-adjusted procedures to
      compare the performance of surgeons. One such risk-adjusted statistic is the
      standardized mortality ratio (SMR), which measures the performance of a surgeon
      adjusted for the risks of patients assuming the average performance of a group of
      surgeons. Unlike the traditional SMR which is defined based on a population, this
      SMR is a random variable. Thus, all existing results for the traditional SMR are
      not valid unless the sample is large enough to be considered a population. In
      this paper, we develop two risk-adjusted procedures for comparing the performance
      of surgeons. The asymptotic distributions of the test statistics are derived. We
      also use the bootstrap procedure to estimate finite-sample distributions. Both
      probability of type I error and power of these procedures are investigated.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28436051
TI  - A novel mass spectrometry-based method for simultaneous determination of
      asymmetric and symmetric dimethylarginine, l-arginine and l-citrulline optimized
      for LC-MS-TOF and LC-MS/MS.
AB  - Nitric oxide (NO) is a regulatory molecule involved in many biological processes.
      NO is produced by nitric oxide synthase by conversion of l-arginine to l
      citrulline. l-Arginine methylated derivatives, asymmetric and symmetric
      dimethylarginines (asymmetric dimethylarginine, ADMA, and symmetric
      dimethylarginine, SDMA), regulate l-arginine availability and the activity of
      nitric oxide synthase. As such, they have been frequently investigated as
      potential biomarkers in pathologies associated with dysfunctions in NO synthesis.
      Here, we present a new multistep analytical methodology based on liquid
      chromatography combined with mass spectrometry for the accurate identification of
      l-arginine, l-citrulline, ADMA and SDMA. Compounds are measured as stable
      2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous
      analysis of all compounds through chromatographic separation of ADMA and SDMA
      using a reverse-phase column. Serum aliquots (100 MUL) were spiked with isotope
      labeled internal standards and sodium carbonate buffer. The derivatization
      process was carried out at 25 degrees C for 10 minu using pentafluorobenzoyl
      chloride as derivatization reagent. Calibration demonstrated good linearity (R2 
      = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67-99.91%) and
      precision (1.92-11.8%) were observed for the quality control samples. The
      applicability of the method was evaluated in a cohort of angiological patients
      and healthy volunteers. The method discerned significantly lower l-arginine and l
      citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a
      useful tool in quantitative analysis of l-arginine, ADMA, SDMA and l-citrulline.

PMID- 28436052
TI  - Clustering multiply imputed multivariate high-dimensional longitudinal profiles.
AB  - In this paper, we propose a method to cluster multivariate functional data with
      missing observations. Analysis of functional data often encompasses dimension
      reduction techniques such as principal component analysis (PCA). These techniques
      require complete data matrices. In this paper, the data are completed by means of
      multiple imputation, and subsequently each imputed data set is submitted to a
      cluster procedure. The final partition of the data, summarizing the partitions
      obtained for the imputed data sets, is obtained by means of ensemble clustering.
      The uncertainty in cluster membership, due to missing data, is characterized by
      means of the agreement between the members of the ensemble and fuzziness of the
      consensus clustering. The potential of the method was brought out on the heart
      failure (HF) data. Daily measurement for four biomarkers (heart rate, diastolic,
      and systolic blood pressure, weight) were used to cluster the patients. To
      normalize the distributions of the longitudinal outcomes, the data were
      transformed with a natural logarithm function. A cubic spline base with 69 basis
      functions was employed to smooth the profiles. The proposed algorithm indicates
      the existence of a latent structure and divides the HF patients into two
      clusters, showing a different evolution in blood pressure values and weight. In
      general, cluster results are sensitive to choices made. Likewise for the proposed
      approach, alternative choices for the distance measure, procedure to optimize the
      objective function, choice of the scree-test threshold, or the number of
      principal components, to be used in the approximation of the surrogate density,
      could all influence the final partition. For the HF data set, the final partition
      depends on the number of principal components used in the procedure.

PMID- 28436053
TI  - Measuring family-centred practices of professionals in early intervention
      services in Taiwan.
AB  - BACKGROUND: Family-centred practices emphasize professional supports for forming
      partnerships with families in early intervention. The Measure of Processes of
      Care for Service Providers (MPOC-SP) measures the perceptions of paediatric
      service providers in supporting children and families. This study aimed to
      establish reliability of the Chinese version of the MPOC-SP (C-MPOC-SP) and to
      examine professional perceptions of family-centred practices in relation to
      professional discipline and years of experience. METHODS: A convenience sample of
      94 physical therapists, occupational therapists, speech-language pathologists,
      social workers and early childhood educators completed the C-MPOC-SP. Thirty
      seven professionals completed the measure a second time within 2-4 weeks for test
      retest reliability. Internal consistency and test-retest reliability were
      examined by Cronbach's alpha and intra-class correlation coefficient. Comparisons
      were made across professional disciplines by multivariate analyses of variance
      followed by analyses of variance. Relationships between years of experience and
      ratings of family-centred practices were examined by Pearson's correlation
      coefficients (r). RESULTS: Cronbach's alpha for items on each of the four scales
      of the C-MPOC-SP ranged from 0.80 to 0.92, indicating adequate internal
      consistency. Intra-class correlation coefficient between the initial and repeat
      completion of the C-MPOC-SP for each scale ranged from 0.56 to 0.77, indicating
      adequate to excellent test-retest reliability. Mean ratings for the Communicating
      Specific Information were significantly higher for physical therapists,
      occupational therapists and speech-language pathologists than for social workers
      (P = 0.001). The C-MPOC-SP scores were positively correlated with years of
      experience for all four scales (r = 0.23-0.38; P < 0.05). CONCLUSIONS: This study
      established adequate internal consistency and adequate to excellent test-retest
      reliability of the C-MPOC-SP in measuring perceptions of family centeredness of
      early intervention service providers. Cross-discipline differences were found in
      communicating specific information about the child. Higher perceptions of family
      centeredness were associated with more years of experience. The results support
      the utility of the C-MPOC-SP in professional education and programme evaluation
      of early intervention services in Taiwan.

PMID- 28436054
TI  - Low-Cost Manufacturing of Bioresorbable Conductors by Evaporation-Condensation
      Mediated Laser Printing and Sintering of Zn Nanoparticles.
AB  - Currently, bioresorbable electronic devices are predominantly fabricated by
      complex and expensive vacuum-based integrated circuit (IC) processes. Here, a low
      cost manufacturing approach for bioresorbable conductors on bioresorbable polymer
      substrates by evaporation-condensation-mediated laser printing and sintering of
      Zn nanoparticle is reported. Laser sintering of Zn nanoparticles has been
      technically difficult due to the surface oxide on nanoparticles. To circumvent
      the surface oxide, a novel approach is discovered to print and sinter Zn
      nanoparticle facilitated by evaporation-condensation in confined domains. The
      printing process can be performed on low-temperature substrates in ambient
      environment allowing easy integration on a roll-to-roll platform for economical
      manufacturing of bioresorbable electronics. The fabricated Zn conductors show
      excellent electrical conductivity (~1.124 * 106 S m-1 ), mechanical durability,
      and water dissolvability. Successful demonstration of strain gauges confirms the
      potential application in various environmentally friendly sensors and circuits.

PMID- 28436055
TI  - Implantation Window and Angiogenesis.
AB  - In recent decades, infertility is one of the health problems worldwide. One of
      the most crucial events in reproductive period is implantation window (IW). In
      the time after IW period, the embryo cannot connect to the endometrium; therefore
      the most critical issue for successful implantation is timely entrance of embryo
      to the uterine cavity during the IW. Implantation failure is responsible for many
      cases of infertility and is the most important limiting factor for achieving a
      successful outcome using the assisted reproductive techniques (ART). The aim of
      this study was to investigate the receptivity of the endometrium and factors
      affecting it with emphasizing on the role of angiogenesis. Interaction between
      the embryo and the endometrium is affected by molecular interactions among
      cytokines, growth factors, hormones, and cell adhesion molecules, causing
      endometrial receptivity. Also, angiogenesis is a process that has an important
      role in human implantation. Estrogen and progesterone hormones are two important
      regulation keys in angiogenesis and implantation process. It is expected that
      effective and stimulating drugs of angiogenesis can improve the characteristics
      of endometrial receptivity and prevent implantation failure in ART. It is hoped
      that with recent advances in the field of molecular medicine, improvement of
      angiogenesis in human endometrium and prevention of the implantation failure be
      achieved. Here, we summarized various factors could affect on endometrial
      receptivity and the role of them on angiogenesis. J. Cell. Biochem. 118: 4141
      4151, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436056
TI  - Elemental ion release and cytotoxicity of antimicrobial acrylic resins
      incorporated with nanomaterial.
AB  - OBJECTIVES: This study evaluated the release of ions and the cytotoxicity of
      acrylic resins incorporated with silver vanadate decorated with silver
      nanoparticles (AgVO3 ). BACKGROUND: The inhibition of the accumulation of
      microorganisms on the resins is critical in preventing diseases. However, the
      hypothesis is that the release of ions from the incorporation of AgVO3 may be
      important in biocompatibility. MATERIALS AND METHODS: Specimens of
      autopolymerising (AP) and heat-polymerising resin (HP) with AgVO3 were prepared
      and immersed in culture medium. The release of silver ions (Ag) and vanadium (V)
      was evaluated by mass spectrometry with inductively coupled plasma (ICP-MS) (n=9)
      and the cell viability of fibroblasts L929 by MTT (3-[4,5-dimethylthiazol- 2yl]
      2,5-diphenyltetrazolium bromide) (n=12). The results were evaluated with analysis
      of variance (ANOVA), Tukey and Pearson correlation test (alpha=.05). RESULTS: The
      groups containing AgVO3 presented a difference in relation to the control (0%)
      regarding the release of Ag and V (P<.0001). All groups showed a reduction in
      L929 viability when compared with the cellular control (100%) (P<.0001). In
      comparison with the control resins for HP, a reduction in the metabolism of cells
      occurred starting at 2.5% and for AP at 5% (P<.0001). A positive correlation was
      found between the concentration of AgVO3 and the ion release, and a negative
      between the ion release and the cell viability. CONCLUSIONS: Significant numbers
      of Ag and V ions were released from resins with higher concentrations of AgVO3 ,
      presenting cytotoxicity for cells, suggesting that the use of low concentrations
      is indicated to avoid risks to patients.

PMID- 28436057
TI  - The effect of pH on chronic zinc toxicity differs between daphnid species:
      Development of a preliminary chronic zinc Ceriodaphnia dubia bioavailability
      model.
AB  - In the present study, we observed that the chronic Zn Daphnia magna biotic ligand
      model (BLM) could not accurately predict the chronic Zn toxicity to Ceriodaphnia
      dubia in a series of (modified) field waters, although the intrinsic
      sensitivities of the D. magna BLM were specifically calibrated on the sensitivity
      of C. dubia. Moreover, it was observed that the D. magna BLM underestimated the
      effect of pH on the toxicity of the free Zn2+ ion. A preliminary species-specific
      chronic Zn C. dubia bioavailability model was developed based on the data. The
      preliminary Zn C. dubia bioavailability model was shown to predict Zn toxicity to
      C. dubia in a series of natural waters with pH ranging between 7 and 8.3 with
      reasonable accuracy. The difference in the effect of pH on Zn2+ toxicity between
      D. magna and C. dubia (2 phylogenetically closely related species) suggested by
      our results deserves further attention because of the importance of the cross
      species application of bioavailability models in ecological risk-assessment
      procedures and environmental quality standard derivations for metals. Environ
      Toxicol Chem 2017;36:2750-2755. (c) 2017 SETAC.

PMID- 28436058
TI  - Stabilizing the MXenes by Carbon Nanoplating for Developing Hierarchical
      Nanohybrids with Efficient Lithium Storage and Hydrogen Evolution Capability.
AB  - The MXenes combining hydrophilic surface, metallic conductivity and rich surface
      chemistries represent a new family of 2D materials with widespread applications.
      However, their poor oxygen resistance causes a great loss of electronic
      properties and surface reactivity, which significantly inhibits the fabrication,
      the understanding of the chemical nature and full exploitation of the potential
      of MXene-based materials. Herein we report a facile carbon nanoplating strategy
      for efficiently stabilizing the MXenes against structural degradation caused by
      spontaneous oxidation, which provides a material platform for developing MXene
      based materials with attractive structure and properties. Hierarchical MoS2 /Ti3
      C2 -MXene@C nanohybrids with excellent structural stability, electrical
      properties and strong interfacial coupling are fabricated by assembling carbon
      coated few-layered MoS2 nanoplates on carbon-stabilized Ti3 C2 MXene, exhibiting
      exceptional performance for Li storage and hydrogen evolution reaction (HER).
      Remarkably, ultra-long cycle life of 3000 cycles with high capacities but
      extremely slow capacity loss of 0.0016% per cycle is achieved for Li storage at a
      very high rate of 20 A g-1 . They are also highly active HER electrocatalyst with
      very positive onset potential, low overpotential and long-term stability in
      acidic solution. Superb properties highlight the great promise of MXene-based
      materials in cornerstone applications of energy storage and conversion.

PMID- 28436059
TI  - High-Performance Respiration-Based Biocell Using Artificial Nanochannel
      Regulation.
AB  - Based on electron and proton transfer events occurring in biological respiration,
      a mitochondria-based biocell is constructed by combining with artificial
      nanochannels. In this biocell, mitochondria transfer electrons to the working
      electrode and pump protons into the electrolyte through the tricarboxylic acid
      cycle. The nanochannels provide passages for protons to transport along the
      transmembrane concentration gradient to consume electrons on the counter
      electrode, forming a continuous and stable current. Furthermore, the proton
      transmembrane transport behavior could be modulated by regulating the
      permeability area and surface charge of nanochannels. A high-performance biocell
      is obtained when equipped with the optimized nanochannels, which produces a
      current of ~3.1 mA cm-2 , a maximum power of ~0.91 mW cm-2 , and a lifetime over
      60 h. This respiratory-based biocell shows great potential for the efficient
      utilization of bioelectricity.

PMID- 28436060
TI  - Pneumatosis intestinalis in a cohort of children with neurological impairment: A
      patient group with a management dilemma.
AB  - AIM: Pneumatosis intestinalis (PI) is uncommon in school-age children. We studied
      a cohort of neurologically impaired school-age children with PI to formulate an
      optimum management plan. METHODS: We retrospectively studied all school-age
      children who were referred to paediatric surgeons with radiological evidence of
      PI identified between 2011 and 2015. We analysed data on patient demographics,
      medications, feeding, associated comorbidities, presentation, investigations and
      treatments. RESULTS: Five patients (3F:2M) with a median age of 7 years (range 5
      9) were referred for surgical opinion with the evidence of pneumatosis on their
      abdominal X-rays. Four of them had associated pneumoperitoneum. All children had
      neurological impairment significant enough to make them unable to communicate
      clearly. Four patients were gastrostomy fed, one was jejunally fed. Four children
      had recurrent episodes of pneumatosis. Four patients had surgery at the initial
      presentation where colonic pneumatosis was detected; however, there was no
      evidence of bowel ischaemia or perforation despite of the presence of
      pneumoperitoneum. Recurrent episodes were successfully managed conservatively
      even in the presence of pneumoperitoneum. CONCLUSION: In neurologically impaired
      school-age children, the presence of pneumatosis and pneumoperitoneum does not
      mandate bowel ischaemia or perforation and therefore could be successfully
      managed conservatively without the need for surgery.

PMID- 28436061
TI  - Resistance exercise reduces memory impairment induced by monosodium glutamate in
      male and female rats.
AB  - NEW FINDINGS: What is the central question of this study? Monosodium glutamate
      causes cognitive impairment. Does resistance exercise improve the performance of
      rats treated with monosodium glutamate? What is the main finding and its
      importance? Resistance exercise is effective against monosodium glutamate-induced
      memory impairment in male and female rats. Monosodium glutamate (MSG), a flavour
      enhancer in diets, causes cognitive impairment in rodents. Exercise has been
      reported to protect against impairment of memory in humans. In this study, we
      investigated whether resistance exercise improves the performance of male and
      female rats treated with MSG in tests of memory and motor co-ordination. Wistar
      rats received MSG [4 g (kg body weight)-1  day-1 , s.c.] from postnatal day 1 to
      10. At postnatal day 60, the animals started a resistance exercise protocol in an
      80 deg inclined vertical ladder apparatus and performed it during 7 weeks. Rats
      performed object recognition and location memory tests. Resistance exercise
      reduced impairment in motor co-ordination of male and female rats treated with
      MSG. Resistance exercise was effective against the decrease in exploratory
      preference in the long-term recognition memory for novel objects of male rats
      treated with MSG. In MSG-treated female rats, resistance exercise was effective
      against the decrease in exploratory preference in the novel object location test.
      The exploratory preference of female rats in the long-term recognition memory
      test was similar in all groups. The short-term memory was not altered by MSG or
      resistance exercise in male and female rats. This study demonstrates that MSG
      affected the memory of male and female rats in different ways. Resistance
      exercise was effective against the decrease in recognition for male rats and in
      location memory for female rats treated with MSG. This report demonstrates the
      beneficial effects of resistance exercise against the prejudice of motor
      condition and impairment of memory induced by MSG in male and female rats.

PMID- 28436062
TI  - Ultrahigh Average Thermoelectric Figure of Merit, Low Lattice Thermal
      Conductivity and Enhanced Microhardness in Nanostructured (GeTe)x (AgSbSe2 )100
      x.
AB  - Waste heat sources are generally diffused and provide a range of temperatures
      rather than a particular temperature. Thus, thermoelectric waste heat to
      electricity conversion requires a high average thermoelectric figure of merit
      (ZTavg ) of materials over the entire working temperature along with a high peak
      thermoelectric figure of merit (ZTmax ). Herein an ultrahigh ZTavg of 1.4 for
      (GeTe)80 (AgSbSe2 )20 [TAGSSe-80, T=tellurium, A=antimony, G=germanium, S=silver,
      Se=selenium] is reported in the temperature range of 300-700 K, which is one of
      the highest values measured amongst the state-of-the-art Pb-free polycrystalline
      thermoelectric materials. Moreover, TAGSSe-80 exhibits a high ZTmax of 1.9 at 660
      K, which is reversible and reproducible with respect to several heating-cooling
      cycles. The high thermoelectric performance of TAGSSe-x is attributed to
      extremely low lattice thermal conductivity (kappalat ), which mainly arises due
      to extensive phonon scattering by hierarchical nano/meso-structures in the TAGSSe
      x matrix. Addition of AgSbSe2 in GeTe results in kappalat of ~0.4 W mK-1 in the
      300-700 K range, approaching to the theoretical minimum limit of lattice thermal
      conductivity (kappamin ) of GeTe. Additionally, (GeTe)80 (AgSbSe2 )20 exhibits a
      higher Vickers microhardness (mechanical stability) value of ~209 kgf mm-2
      compared to the other state-of-the-art metal chalcogenides, making it an
      important material for thermoelectrics.

PMID- 28436063
TI  - Placental histology findings in relation to pre-eclampsia: implications for
      interpretation of retrospective studies.

PMID- 28436064
TI  - The changing landscape of cervical screening-What does the future hold for
      primary care?
AB  - The landscape of cervical cancer prevention is changing in many countries thanks
      to the introduction of vaccination against high-risk types of human
      papillomavirus (HPV) and the incorporation of HPV DNA testing into cervical
      screening algorithms. In addition to this, uptake of screening is falling year on
      year in the UK and elsewhere. These factors present challenges and opportunities
      for health professionals working in primary care-in terms of communicating
      programmatic changes to women; responding to questions about the meaning and
      implications of HPV test results; and delivering interventions to increase
      screening uptake.

PMID- 28436065
TI  - Fetal bradycardia associated with maternal hypothermia after fetoscopic repair of
      neural tube defect.

PMID- 28436066
TI  - Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli
      sani cohort and cellular models.
AB  - Meta-analytic data on the effect of coffee in prostate cancer risk are
      controversial. Caffeine as a bioactive compound of coffee has not yet been
      studied in deep in vitro. Our study aimed at evaluating in a population cohort
      the effect of Italian-style coffee consumption on prostate cancer risk and at
      investigating in vitro the potential antiproliferative and antimetastatic
      activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli-sani
      cohort aged >=50 years were followed for a mean of 4.24 +/- 1.35 years and 100
      new prostate cancer cases were identified. The European Prospective Investigation
      into Cancer and Nutrition-Food Frequency Questionnaire was used for the dietary
      assessment and the evaluation of Italian-style coffee consumption. Two human
      prostate cancer cell lines, PC-3 and DU145, were tested with increasing
      concentrations of caffeine, and their proliferative/metastatic features were
      evaluated. The newly diagnosed prostate cancer participants presented lower
      coffee consumption (60.1 +/- 51.3 g/day) compared to the disease-free population
      (74.0 +/- 51.7 g/day) (p < 0.05). Multiadjusted analysis showed that the subjects
      at highest consumption (>3 cups/day) had 53% lower prostate cancer risk as
      compared to participants at the lowest consumption (0-2 cups/day) (p = 0.02).
      Both human prostate cancer cell lines treated with caffeine showed a significant
      reduction in their proliferative and metastatic behaviors (p < 0.05). In
      conclusion, reduction by Italian-style coffee consumption of prostate cancer risk
      (>3 cups/day) was observed in epidemiological level. Caffeine appeared to exert
      both antiproliferative and antimetastatic activity on two prostate cancer cell
      lines, thus providing a cellular confirmation for the cohort study results.

PMID- 28436067
TI  - Significant Enhancement of C2 H2 /C2 H4 Separation by a Photochromic Diarylethene
      Unit: A Temperature- and Light-Responsive Separation Switch.
AB  - A dual temperature- and light-responsive C2 H2 /C2 H4 separation switch in a
      diarylethene metal-organic framework (MOF) is presented. At 195 K and 100 kPa
      this MOF shows ultrahigh C2 H2 /C2 H4 selectivity of 47.1, which is almost 21.4
      times larger than the corresponding value of 2.2 at 293 K and 100 kPa, or 15.7
      times larger than the value of 3.0 for the material under UV at 195 K and 100
      kPa. The origin of this unique control in C2 H2 /C2 H4 selectivity, as unveiled
      by density functional calculations, is due to a guest discriminatory gate-opening
      effect from the diarylethene unit.

PMID- 28436068
TI  - Dinitrogen Splitting Coupled to Protonation.
AB  - The coupling of electron- and proton-transfer steps provides a general concept to
      control the driving force of redox reactions. N2 splitting of a molybdenum
      dinitrogen complex into nitrides coupled to a reaction with Bronsted acid is
      reported. Remarkably, our spectroscopic, kinetic, and computational mechanistic
      analysis attributes N-N bond cleavage to protonation in the periphery of an amide
      pincer ligands rather than the {Mo-N2 -Mo} core. The strong effect on electronic
      structure and ultimately the thermochemistry and kinetic barrier of N-N bond
      cleavage is an unusual case of a proton-coupled metal-to-ligand charge transfer
      process, highlighting the use of proton-responsive ligands for nitrogen fixation.

PMID- 28436069
TI  - The ePrep-System: A new electrophoretic approach for DNA isolation from
      biological samples.
AB  - We present a new free-flow electrophoretic separation system that extends the
      established concepts of nucleic acid migration in an electric field to a broadly
      applicable preparative scale. The system comprises a disposable flow tube in
      which the target nucleic acids are separated from impurities by a balanced
      combination of electrophoretic migration and counter-streaming electroosmotic
      flow under the influence of an applied external electric field. Despite the
      complex theoretical background the introduced electrophoretic technology offers
      simple hardware setup and handling protocols. A variable number of small and
      disposable flow tubes can be processed in parallel, which largely eliminates the
      cumulative increase in extraction times inherent to batch processing methods and
      allows faster throughput of intermediate sample numbers. We demonstrate easy
      isolation of nucleic acids without user interaction during the run by using
      existing and well established lysis chemistries. Sample loading is realized by
      concentrated transfer of DNA-loaded magnetic beads from a lysis reaction into the
      extraction flow tube. The present study centers on the development of a
      functional model for the device and the flow tube as well as a preliminary
      standard extraction protocol. The system is compatible with a broad range of
      sample types and we present proof of principle data demonstrating its suitability
      for biomarker detection in translational research applications.

PMID- 28436071
TI  - Correct procedure for uploading information on new taxonomic names to ZooBank.

PMID- 28436072
TI  - Real-time individualization of the unified model of performance.
AB  - Existing mathematical models for predicting neurobehavioural performance are not
      suited for mobile computing platforms because they cannot adapt model parameters
      automatically in real time to reflect individual differences in the effects of
      sleep loss. We used an extended Kalman filter to develop a computationally
      efficient algorithm that continually adapts the parameters of the recently
      developed Unified Model of Performance (UMP) to an individual. The algorithm
      accomplishes this in real time as new performance data for the individual become
      available. We assessed the algorithm's performance by simulating real-time model
      individualization for 18 subjects subjected to 64 h of total sleep deprivation
      (TSD) and 7 days of chronic sleep restriction (CSR) with 3 h of time in bed per
      night, using psychomotor vigilance task (PVT) data collected every 2 h during
      wakefulness. This UMP individualization process produced parameter estimates that
      progressively approached the solution produced by a post-hoc fitting of model
      parameters using all data. The minimum number of PVT measurements needed to
      individualize the model parameters depended upon the type of sleep-loss
      challenge, with ~30 required for TSD and ~70 for CSR. However, model
      individualization depended upon the overall duration of data collection, yielding
      increasingly accurate model parameters with greater number of days.
      Interestingly, reducing the PVT sampling frequency by a factor of two did not
      notably hamper model individualization. The proposed algorithm facilitates real
      time learning of an individual's trait-like responses to sleep loss and enables
      the development of individualized performance prediction models for use in a
      mobile computing platform.

PMID- 28436073
TI  - Academic and private practice partnerships in veterinary radiology residency
      training.
AB  - As veterinary radiologists devote greater time to telemedicine consultation,
      residency training must evolve to reflect the skills of these services. The
      contribution of private practice/consultant radiologists to residency training
      has traditionally been minimal but academic and private practice partnerships in
      education and research can provide the framework for a well-rounded residency.
      These partnerships can also lessen the impact of workforce shortages in academia
      and provide financial compensation to academicians through external consultation.
      The purpose of this commentary is to review existing collaborative interactions
      between academic and private practice veterinary radiologists; with a focus on
      ways to sustain, improve, and cautiously increase the number of veterinary
      radiology training programs.

PMID- 28436074
TI  - An evaluation of the mixed pediatric unit for blood loss replacement in pediatric
      craniofacial surgery.
AB  - BACKGROUND: Surgical correction for craniosynostosis is often associated with
      significant perioperative hemorrhage. We implemented a transfusion strategy with
      a strict protocol including transfusion triggers, frequent assessment of
      coagulation tests, and the use of a novel transfusion unit, the mixed pediatric
      unit. AIM: The aim of the study was to evaluate if the applied transfusion
      strategy could reduce total blood loss and number of blood donors. METHODS:
      Children <1 year old admitted for craniosynostosis surgery were included for the
      study. On the day before surgery, an adult red blood cell unit was mixed with
      plasma and split into two mixed pediatric units-one intended for intraoperative
      use and the other saved for the postoperative period. A series of blood samples
      were obtained for standard coagulation parameters as well as thromboelastography
      to evaluate potential coagulopathy. Estimated blood loss, the number of
      additional standard packed red cell units opened in the first 24 h after surgery,
      the volume of fluid administered, and the total transfusion volumes were compared
      to a historical control group with similar age and characteristics. RESULTS:
      Nineteen infants were included in the study group, and were compared to 21
      historical controls. There was a significant reduction of intraoperative
      transfusion volume. Twelve patients were transfused postoperatively, but in 8 of
      these additional exposure to packed red cell donor blood was avoided by using the
      saved mixed pediatric unit. In the historical controls, a total of 10 packed red
      cell units were used in nine patients postoperatively. No additional transfusions
      of plasma, platelets, fibrinogen, or tranexamic acid were needed in either group,
      and the coagulation parameters including thromboelastography remained within
      their respective normal ranges in the study group. CONCLUSION: For craniofacial
      surgery in infants, moderate perioperative blood loss and avoidance of
      coagulopathy is possible when a multifactorial approach is implemented. In this
      setting, intraoperative, but not total perioperative blood loss was reduced with
      the studied protocol. The study indicates that there may be a role for mixed
      pediatric units to reduce exposure to multiple donors although the reduction in
      total donor exposure was not significant.

PMID- 28436076
TI  - Unclicking the Click: Metal-Assisted Mechanochemical Cycloreversion of Triazoles
      Is Possible.
AB  - The mechanochemical cycloreversion of 1,2,3-triazole compounds, which serve as
      unusually stable building blocks in materials and biomolecular chemistry as a
      result of mild "click chemistry", remains puzzling. We show that the hitherto
      discussed straight-forward retro-click mechanism of the 1,4-disubstituted isomer,
      even if CuI catalyzed, can be ruled out in view of more favorable activation free
      energies of destructive pathways. In stark contrast, the 1,5-regioiomer can
      undergo cycloreversion under rather mild mechanochemical conditions owing to its
      favorable response to the external force in conjunction with standard RuII
      catalysis.

PMID- 28436075
TI  - Does a meso-caval shunt have positive effects in a pig large-for-size liver
      transplantation model?
AB  - In pediatric liver transplantations with LFS grafts, higher incidences of graft
      dysfunction probably occur due to IRI. It was postulated that increasing the
      blood supply to the graft by means of a meso-caval shunt could ameliorate the
      IRI. Eleven pigs underwent liver transplantation and were divided into two
      groups: LFS and LFS+SHUNT group. A series of flowmetric, metabolic, histologic,
      and molecular studies were performed. No significant metabolic differences were
      observed between the groups. One hour after reperfusion, portal flow was
      significantly lower in the recipients than in the donors, proving that the graft
      was maintained in low portal blood flow, although the shunt could promote a
      transient increase in the portal blood flow and a decrease in the arterial flow.
      Finally, it was verified that the shunt promoted a decrease in inflammation and
      steatosis scores and a decrease in the expression of the eNOS gene (responsible
      for the generation of nitric oxide in the vascular endothelium) and an increase
      in the expression of the proapoptotic gene BAX. The meso-caval shunt was
      responsible for some positive effects, although other deleterious flowmetric and
      molecular alterations also occurred.

PMID- 28436077
TI  - Neuroprotective effect of epidermal growth factor in experimental acrylamide
      neuropathy: an electrophysiological approach.
AB  - The neuroprotective effect of epidermal growth factor (EGF) has been documented
      in different contexts, but its potential benefits in peripheral neuropathies have
      been little studied. We investigated the neuroprotective action of EGF in
      experimental neuropathy induced by acrylamide (ACR). Mice and rats were treated
      chronically with acrylamide for 6 and 8 weeks, respectively. Concurrently they
      received EGF in daily doses of 1 and 5 mg/kg in mice and 3 mg/kg in rats, or
      saline (PBS). ACR severely affected the neurological score, the muscle strength,
      and the muscle potential M, in mice, as well as F-waves (F-Wii), sensory
      potentials (SPii), and apomorphine-induced penile erection, in rats. EGF reduced
      the ACR effects in both species. A dose-dependent effect of EGF was manifested in
      the proportion of diseased animals at the end of treatments, as well as in the
      reduction of M amplitude throughout the treatment. F-Wii parameters were less
      protected by EGF than SP. The results show a protective effect of EGF in
      acrylamide-induced neuropathy and support previous studies concerning the
      neuroprotective action of this peptide.

PMID- 28436078
TI  - Oxygen isotope fractionations across individual leaf carbohydrates in grass and
      tree species.
AB  - Almost no delta18 O data are available for leaf carbohydrates, leaving a gap in
      the understanding of the delta18 O relationship between leaf water and cellulose.
      We measured delta18 O values of bulk leaf water (delta18 OLW ) and individual
      leaf carbohydrates (e.g. fructose, glucose and sucrose) in grass and tree species
      and delta18 O of leaf cellulose in grasses. The grasses were grown under two
      relative humidity (rH) conditions. Sucrose was generally 18 O-enriched compared
      with hexoses across all species with an apparent biosynthetic fractionation
      factor (epsilonbio ) of more than 270/00 relative to delta18 OLW , which might be
      explained by isotopic leaf water and sucrose synthesis gradients. delta18 OLW and
      delta18 O values of carbohydrates and cellulose in grasses were strongly related,
      indicating that the leaf water signal in carbohydrates was transferred to
      cellulose (epsilonbio  = 25.10/00). Interestingly, damping factor pex px , which
      reflects oxygen isotope exchange with less enriched water during cellulose
      synthesis, responded to rH conditions if modelled from delta18 OLW but not if
      modelled directly from delta18 O of individual carbohydrates. We conclude that
      delta18 OLW is not always a good substitute for delta18 O of synthesis water due
      to isotopic leaf water gradients. Thus, compound-specific delta18 O analyses of
      individual carbohydrates are helpful to better constrain (post-)photosynthetic
      isotope fractionation processes in plants.

PMID- 28436079
TI  - (L)2 C2 P2 : Dicarbondiphosphide Stabilized by N-Heterocyclic Carbenes or Cyclic
      Diamido Carbenes.
AB  - Carbon phosphides, Cn Pm , may have highly promising electronic, optical, and
      mechanical properties, but they are experimentally almost unexplored materials.
      Phosphaheteroallenes stabilized by N-heterocyclic carbenes undergo a one-electron
      reduction to yield compounds of the type (L)2 C2 P2 with diverse structures. The
      use of imidazolylidenes as ligands L give complexes with a central four-membered
      ring C2 P2 , while more electrophilic cyclic diamidocarbenes (DAC) give a
      compound with an acyclic pi-conjugated CP-PC unit. Cyclic C2 P2 compounds are
      best described as non-Kekule molecules that are stabilized by coordination to the
      NHC ligands NHC->(C2 P2 )<-NHC. These species can be easily oxidized to give
      stable radical cations [(NHC)2 C2 P2 ]+. . The remarkably stable molecules with
      an acylic C2 P2 core are best described with electron-sharing bonds (DAC)=C=P
      P=C=(DAC).

PMID- 28436081
TI  - A Practical High-Energy Cathode for Sodium-Ion Batteries Based on Uniform P2
      Na0.7 CoO2 Microspheres.
AB  - Layered metal oxides have attracted increasing attention as cathode materials for
      sodium-ion batteries (SIBs). However, the application of such cathode materials
      is still hindered by their poor rate capability and cycling stability. Here, a
      facile self-templated strategy is developed to synthesize uniform P2-Na0.7 CoO2
      microspheres. Due to the unique microsphere structure, the contact area of the
      active material with electrolyte is minimized. As expected, the P2-Na0.7 CoO2
      microspheres exhibit enhanced electrochemical performance for sodium storage in
      terms of high reversible capacity (125 mAh g-1 at 5 mA g-1 ), superior rate
      capability and long cycle life (86 % capacity retention over 300 cycles).
      Importantly, the synthesis method can be easily extended to synthesize other
      layered metal oxide (P2-Na0.7 MnO2 and O3-NaFeO2 ) microspheres.

PMID- 28436080
TI  - Genotype-specific pathogenic effects in human dilated cardiomyopathy.
AB  - KEY POINTS: Mutations in genes encoding cardiac troponin I (TNNI3) and cardiac
      troponin T (TNNT2) caused altered troponin protein stoichiometry in patients with
      dilated cardiomyopathy. TNNI3p.98trunc resulted in haploinsufficiency, increased
      Ca2+ -sensitivity and reduced length-dependent activation. TNNT2p.K217del caused
      increased passive tension. A mutation in the gene encoding Lamin A/C (LMNAp.R331Q
      ) led to reduced maximal force development through secondary disease remodelling
      in patients suffering from dilated cardiomyopathy. Our study shows that different
      gene mutations induce dilated cardiomyopathy via diverse cellular pathways.
      ABSTRACT: Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric
      and non-sarcomeric genes. In this study we defined the pathogenic effects of
      three DCM-causing mutations: the sarcomeric mutations in genes encoding cardiac
      troponin I (TNNI3p.98truncation ) and cardiac troponin T (TNNT2p.K217deletion ;
      also known as the p.K210del) and the non-sarcomeric gene mutation encoding lamin
      A/C (LMNAp.R331Q ). We assessed sarcomeric protein expression and phosphorylation
      and contractile behaviour in single membrane-permeabilized cardiomyocytes in
      human left ventricular heart tissue. Exchange with recombinant troponin complex
      was used to establish the direct pathogenic effects of the mutations in TNNI3 and
      TNNT2. The TNNI3p.98trunc and TNNT2p.K217del mutation showed reduced expression
      of troponin I to 39% and 51%, troponin T to 64% and 53%, and troponin C to 73%
      and 97% of controls, respectively, and altered stoichiometry between the three
      cardiac troponin subunits. The TNNI3p.98trunc showed pure haploinsufficiency,
      increased Ca2+ -sensitivity and impaired length-dependent activation. The
      TNNT2p.K217del mutation showed a significant increase in passive tension that was
      not due to changes in titin isoform composition or phosphorylation. Exchange with
      wild-type troponin complex corrected troponin protein levels to 83% of controls
      in the TNNI3p.98trunc sample. Moreover, upon exchange all functional deficits in
      the TNNI3p.98trunc and TNNT2p.K217del samples were normalized to control values
      confirming the pathogenic effects of the troponin mutations. The LMNAp.R331Q
      mutation resulted in reduced maximal force development due to disease
      remodelling. Our study shows that different gene mutations induce DCM via diverse
      cellular pathways.

PMID- 28436082
TI  - Tricellulin is a target of the ubiquitin ligase Itch.
AB  - Tricellulin, a member of the tight junction-associated MAGUK protein family,
      preferentially localizes to tricellular junctions in confluent polarized
      epithelial cell layers and is downregulated during the epithelial-mesenchymal
      transition. Posttranslational modifications are assumed to play critical roles in
      the process of downregulation of tricellulin at the protein level. Here, we
      report that the E3 ubiquitin ligase Itch forms a complex with tricellulin and
      thereby enhances its ubiquitination. Pull-down assays confirmed a direct
      interaction between tricellulin and Itch, which is mediated by the Itch WW domain
      and the N-terminus of tricellulin. Experiments in the presence of the proteasome
      inhibitor MG-132 did not show major changes in the levels of ubiquitinated
      tricellulin in epithelial cells, suggesting that ubiquitination is not primarily
      involved in proteasomal degradation of tricellulin, but it appears to be
      important for endocytosis or recycling. In contrast, in HEK-293 cells, MG-132
      caused polyubiquitination. Moreover, we observed that well-differentiated RT-112
      and de-differentiated Cal-29 bladder cancer cells show an inverse expression of
      tricellulin and Itch. We postulate that ubiquitination is an important
      posttranslational modification involved in the determination of the intracellular
      fate of tricellulin deserving of more detailed further investigations into the
      underlying molecular mechanisms and their regulation.

PMID- 28436083
TI  - The added value of world views over self-views: Predicting modest behaviour in
      Eastern and Western cultures.
AB  - Personality research has been focused on different aspects of the self, including
      traits, attitudes, beliefs, goals, and motivation. These aspects of the self are
      used to explain and predict social behaviour. The present research assessed
      generalized beliefs about the world, termed 'social axioms' (Leung et al., ), and
      examined their additive power over beliefs about the self in explaining a
      communal behaviour, that is, modesty. Three studies predicted reported modest
      behaviour among Mainland Chinese, Hong Kong Chinese, East Asian Canadians, and
      European Canadians. In addition to self-reports in Studies 1 and 2, informant
      reports from participants' parents and close friends were collected in Study 3 to
      construct a behavioural composite after examining the resulting multitrait
      multimethod matrix and intraclass correlations. World views (operationalized as
      social axioms) explained additional variance in modest behaviour over and above
      self-views (operationalized as self-efficacy, self-construals, and trait modesty)
      in both Eastern and Western cultures. Variation in reports on three factors of
      modest behaviour was found across self-, parent, and friend perspectives, with
      significant differences across perspectives in self-effacement and other
      enhancement, but not in avoidance of attention-seeking.

PMID- 28436084
TI  - Defining "significant weight loss" in atypical anorexia nervosa.
AB  - OBJECTIVE: Atypical anorexia nervosa (AAN) is defined by the symptoms of anorexia
      nervosa in the presence of "significant weight loss" in individuals who are not
      underweight. Description of current weight in AAN has been limited, significant
      weight loss has not been defined, and the distinction between having AAN versus
      having weight suppression has not been examined. METHOD: Secondary analyses were
      conducted with data from an epidemiological study of women (n = 1,640) and men (n
      = 794). Three definitions of significant weight loss (5, 10, and 15%) for AAN
      were tested in comparisons with controls and a DSM-5 eating disorder group (DSM-5
      ED) on measures of eating pathology and clinical significance using ANCOVA and
      logistic regression, controlling for age and body mass index. Secondary analyses
      compared AAN to a weight suppressed group (WS-only) and a cognitive concerns
      group (COG-only). RESULTS: Across weight loss thresholds, >=25% of adults with
      AAN were currently overweight/obese. At the 5% and 10% definitions, AAN was
      associated with elevated eating pathology and distress relative to controls, WS
      only, and COG-only in women and men. Women with AAN endorsed less eating
      pathology and distress than DSM-5 ED at some weight loss definitions, whereas men
      with AAN did not differ from DSM-5 ED in eating pathology or distress.
      DISCUSSION: Results support that even a 5% weight loss, combined with cognitive
      concerns, may produce a group with a clinically significant eating disorder. AAN
      was observed in both healthy weight and overweight/obese adults, highlighting the
      importance of screening for restrictive eating disorders at all weights.

PMID- 28436085
TI  - Effect of triclosan on anuran development and growth in a larval amphibian growth
      and development assay.
AB  - A larval amphibian growth and development assay was performed to evaluate the
      potential effects of environmentally-relevant concentrations of triclosan (TCS)
      on amphibian development and growth. Xenopus laevis were exposed to TCS 0.0
      (control), 6.3, 12.5 and 25.0 MUg l-1 (estimated maximum tolerable concentration)
      until 10 weeks post-metamorphosis. At median metamorphosis time (Nieuwkoop and
      Faber stage 62), five larvae per replicate were collected for snout-vent length,
      hind limb length and body weight measurements, and histopathological examination
      of thyroid glands. Endpoints evaluated at test termination were based on draft
      guidance (USEPA, ) and included: survival; snout-vent length; body weight;
      gender; nuptial pad development (males); and liver, kidney, gonad and gonadal
      ducts histopathology. Exposure to TCS did not decrease survival, induce general
      signs of toxicity, affect median metamorphosis time or alter sex ratios. Exposure
      to TCS 12.5 and 25 MUg l-1 increased growth during the metamorphic stages
      relative to the control, but did not influence growth during the post-metamorphic
      phase. Overall, several statistically significant findings were found in larvae
      exposed to TCS, such as a decrease in the prevalence of stage 3 Mullerian ducts
      in the anterior trunk sections of TCS 25.0 MUg l-1 dose group females as compared
      to controls; most were not considered toxicologically relevant. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 28436086
TI  - Male clinical norms and sex differences on the Eating Disorder Inventory (EDI)
      and Eating Disorder Examination Questionnaire (EDE-Q).
AB  - OBJECTIVE: Evidence indicates that males account for a significant minority of
      patients with eating disorders (EDs). However, prior research has been limited by
      inclusion of small and predominantly non-clinical samples of males. This study
      aimed to (1) provide male clinical norms for widely used ED measures (Eating
      Disorder Examination Questionnaire [EDE-Q] and Eating Disorder Inventory-3 [EDI
      3]) and (2) examine sex differences in overall ED psychopathology. METHOD:
      Participants were 386 male and 1,487 female patients with an ED diagnosis aged 16
      years and older who completed the EDE-Q and EDI-3 upon admission to a residential
      or partial hospital ED treatment program. RESULTS: Normative data were calculated
      for the EDE-Q (global and subscales) and the EDI-3 (drive for thinness, body
      dissatisfaction, and bulimia). Analyses of variance (ANOVAs) used to examine sex,
      ED diagnosis, and their interaction in relation to overall ED psychopathology
      revealed a consistent pattern of greater severity among females for ED
      psychopathology. DISCUSSION: This study provides clinical norms on the EDE-Q and
      the EDI-3 for males with clinically diagnosed EDs. It is unclear whether the
      greater severity observed in females reflects qualitative differences in ED
      presentation or true quantitative differences in ED severity. Additional research
      examining the underlying nature of these differences and utilizing male-specific
      ED measures with clinical samples is warranted.

PMID- 28436087
TI  - A deeper look at torpedo maculopathy.
AB  - BACKGROUND: Torpedo maculopathy is a rare, congenital maculopathy classically
      diagnosed funduscopically as a 'torpedo-shaped' lesion located temporal to the
      fovea. This case describes a torpedo maculopathy with non-classic optical
      coherence tomographic (OCT) findings and collaborative OCT angiographic (OCTA)
      findings. CASE REPORT: A 60-year-old Caucasian woman presented with a history of
      longstanding distortion and paracentral scotoma of the right eye. She had a
      positive family history of age-related macular degeneration. Visual acuity was
      6/6 in each eye. Dilated fundus examination revealed a torpedo-shaped lesion in
      the right eye with a hypo-pigmented head pointing toward the fovea and a hyper
      pigmented tail end. OCT imaging of the macula of the right eye revealed a
      subretinal cleft space with underlying thinning of the retinal pigment
      epithelium, increased choroidal reflectivity, as well as retinal pigment
      epithelial and choroidal excavation. OCTA choriocapillaris segmentation showed a
      hypo-reflective area associated with the lesion, adjacent to hyper-reflectivity.
      The patient was diagnosed with torpedo maculopathy of the right eye. CONCLUSIONS:
      OCT and OCTA imaging have been instrumental in developing a deeper understanding
      of many maculopathies, allowing for accurate diagnosis of macular conditions.
      Although the aetiology remains unclear, these imaging devices may provide further
      insight into the lesion in torpedo maculopathy.

PMID- 28436088
TI  - Trihydroborates and Dihydroboranes Bearing a Pentacoordinated Phosphorus Atom:
      Double Ring Expansion To Balance the Coordination States.
AB  - The first trihydroborate bearing a pentacoordinated phosphorus atom was
      synthesized as a new P-B bonded compound. Hydride abstraction of the
      trihydroborate gave an intermediary dihydroborane, which showed hydroboration
      reactivity and was trapped with pyridine whilst maintaining the P-B bond. The
      dihydroborane underwent a rearrangement, which involved a double ring expansion
      to compensate for the unbalanced coordination states of the phosphorus and boron
      atoms, to give a new fused bicyclic phosphine-boronate.

PMID- 28436090
TI  - Using augmented reality to teach and learn biochemistry.
AB  - Understanding metabolism and metabolic pathways constitutes one of the central
      aims for students of biological sciences. Learning metabolic pathways should be
      focused on the understanding of general concepts and core principles. New
      technologies such Augmented Reality (AR) have shown potential to improve
      assimilation of biochemistry abstract concepts because students can manipulate 3D
      molecules in real time. Here we describe an application named Augmented Reality
      Metabolic Pathways (ARMET), which allowed students to visualize the 3D molecular
      structure of substrates and products, thus perceiving changes in each molecule.
      The structural modification of molecules shows students the flow and exchange of
      compounds and energy through metabolism. (c) 2017 by The International Union of
      Biochemistry and Molecular Biology, 45(5):417-420, 2017.

PMID- 28436089
TI  - A novel dense granule protein, GRA41, regulates timing of egress and calcium
      sensitivity in Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligate intracellular apicomplexan parasite with high
      seroprevalence in humans. Repeated lytic cycles of invasion, replication, and
      egress drive both the propagation and the virulence of this parasite. Key steps
      in this cycle, including invasion and egress, depend on tightly regulated calcium
      fluxes and, although many of the calcium-dependent effectors have been
      identified, the factors that detect and regulate the calcium fluxes are mostly
      unknown. To address this knowledge gap, we used a forward genetic approach to
      isolate mutants resistant to extracellular exposure to the calcium ionophore
      A23187. Through whole genome sequencing and complementation, we have determined
      that a nonsense mutation in a previously uncharacterised protein is responsible
      for the ionophore resistance of one of the mutants. The complete loss of this
      protein recapitulates the resistance phenotype and importantly shows defects in
      calcium regulation and in the timing of egress. The affected protein, GRA41,
      localises to the dense granules and is secreted into the parasitophorous vacuole
      where it associates with the tubulovesicular network. Our findings support a
      connection between the tubulovesicular network and ion homeostasis within the
      parasite, and thus a novel role for the vacuole of this important pathogen.

PMID- 28436091
TI  - Effects of pre-education combined with a simulation for caring for children with
      croup on senior nursing students.
AB  - Educational outcomes, such as knowledge, confidence in performance, ability in
      nursing practice, and satisfaction with learning methods in caring for children
      with croup, were compared between groups of students that received education
      through simulation combined with pre-education, simulation only, and pre
      education only. In this quasi-experimental design, the educational intervention
      for the experimental group was the pre-education modality. Data from a
      convenience sample of 127 senior nursing students were drawn from three nursing
      schools in South Korea. There were significant differences in the mean scores of
      knowledge, confidence in performance, satisfaction with the learning method, and
      ability in nursing practice between the three groups. Pre-education with
      simulation significantly enhanced students' knowledge, confidence in performance,
      ability in nursing practice, and satisfaction with learning methods compared with
      pre-education or simulation alone. Simulation strategies should focus more on
      enhancing nursing students' learning outcomes.

PMID- 28436092
TI  - Effects of creatine supplementation on cardiac autonomic functions in
      bodybuilders.
AB  - Bodybuilder-type workouts may affect heart rate variability (HRV), which has
      considerable potential to assess the role of autonomic nervous system (ANS). A
      scientifically designed approach is necessary for bodybuilders to achieve better
      results while protecting their health. In this study, we aimed to investigate HRV
      parameters in bodybuilders compared to healthy control subjects and effects of
      creatine supplementation. A total of 48 male participants (16 controls, 16
      supplement (-), 16 supplement (+)) were evaluated in our study. Bodybuilders who
      were taking creatine supplementation were enrolled in supplement (+) group. HRV
      parameters were measured from 24-hour Holter recordings of all participants. When
      mean heart rates were compared with control group (71.5 +/- 12.6 beats/min),
      statistically significant difference was revealed in supplement (-) group (61.8
      +/- 6.8 beats/min; P = 0.022) unlike supplement (+) group (69.63 +/- 14.1
      beats/min; P = 0.650). HRV analyses revealed significant parasympathetic shift in
      supplement (-) group. No significant difference was demonstrated on HRV
      parameters, except high frequency (P = 0.029) in supplement (+) group.
      Conclusively, elevated parasympathetic modulation, which is favorable
      cardiovascular outcome of exercise, was demonstrated in bodybuilders. However,
      our study also revealed that creatine supplementation attenuates this favorable
      effect in ANS by limiting elevation of parasympathetic modulation. Although the
      sympathetic slight shift is attributed to creatine supplementation, it cannot be
      discriminated from the effects of over training.

PMID- 28436093
TI  - Genome-wide association studies to identify rice salt-tolerance markers.
AB  - Salinity is an ever increasing menace that affects agriculture worldwide. Crops
      such as rice are salt sensitive, but its degree of susceptibility varies widely
      between cultivars pointing to extensive genetic diversity that can be exploited
      to identify genes and proteins that are relevant in the response of rice to salt
      stress. We used a diversity panel of 306 rice accessions and collected phenotypic
      data after short (6 h), medium (7 d) and long (30 d) salinity treatment (50 mm
      NaCl). A genome-wide association study (GWAS) was subsequently performed, which
      identified around 1200 candidate genes from many functional categories, but this
      was treatment period dependent. Further analysis showed the presence of cation
      transporters and transcription factors with a known role in salinity tolerance
      and those that hitherto were not known to be involved in salt stress.
      Localization analysis of single nucleotide polymorphisms (SNPs) showed the
      presence of several hundred non-synonymous SNPs (nsSNPs) in coding regions and
      earmarked specific genomic regions with increased numbers of nsSNPs. It points to
      components of the ubiquitination pathway as important sources of genetic
      diversity that could underpin phenotypic variation in stress tolerance.

PMID- 28436094
TI  - Dosimetric validation of a magnetic resonance image gated radiotherapy system
      using a motion phantom and radiochromic film.
AB  - PURPOSE: Magnetic resonance image (MRI) guided radiotherapy enables gating
      directly on the target position. We present an evaluation of an MRI-guided
      radiotherapy system's gating performance using an MRI-compatible respiratory
      motion phantom and radiochromic film. Our evaluation is geared toward validation
      of our institution's clinical gating protocol which involves planning to a target
      volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating
      based on a 3 mm window about the GTV. METHODS: The motion phantom consisted of a
      target rod containing high-contrast target inserts which moved in the superior
      inferior direction inside a body structure containing background contrast
      material. The target rod was equipped with a radiochromic film insert. Treatment
      plans were generated for a 3 cm diameter spherical planning target volume, and
      delivered to the phantom at rest and in motion with and without gating. Both
      sinusoidal trajectories and tumor trajectories measured during MRI-guided
      treatments were used. Similarity of the gated dose distribution to the planned,
      motion-frozen, distribution was quantified using the gamma technique. RESULTS:
      Without gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on
      motion trajectory. Using our clinical standard of repeated breath holds and a
      gating window of 3 mm with 10% target allowed outside the gating boundary, the
      gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and
      10% allowed excursion, all of the patient tumor motion trajectories at actual
      speed resulting in at least 95% gamma pass rate at 4%/3 mm. CONCLUSIONS: Our
      results suggest that the device can be used to compensate respiratory motion
      using a 3 mm gating margin and 10% allowed excursion results in conjunction with
      repeated breath holds. Full clinical validation requires a comprehensive
      evaluation of tracking performance in actual patient images, outside the scope of
      this study.

PMID- 28436095
TI  - Berberine Alleviates Oxidative Stress in Islets of Diabetic Mice by Inhibiting
      miR-106b Expression and Up-Regulating SIRT1.
AB  - Mounting studies have indicated the role of berberine, SIRT1, and oxidative
      stress in diabetes, respectively. However, few studies have demonstrated their
      correlation and regulation function in diabetes. Therefore, the protective effect
      of berberine in diabetic and the underlying core mechanism were investigated in
      the current study. Diabetic mice model in vivo were established. Mouse pancreatic
      beta-cell line NIT-1 cells were treated with 30 mM high glucose to induce
      diabetic condition in vitro. Serum biochemical parameters (glucose, total
      cholesterol, and triglycerides) were detected. Oxidative stress indicators (MDA,
      SOD1), along with miR-106b and SIRT1 expression in islets and cells were also
      assessed. Direct targeting relationship between miR-106b and SIRT1 was discussed
      by dual luciferase reporter gene assay. Diabetic model in vivo and in vitro were
      both established successfully. The expression of serum biochemical parameters was
      increased, and oxidative stress parameters, and miR-106b, SIRT1 were abnormally
      expressed in diabetic mice and NIT-1 cells. Meanwhile, berberine could alleviate
      oxidative stress injury in diabetic progression. Through dual luciferase reporter
      gene assay, we found that SIRT1 was a target gene of miR-106b. In addition, miR
      106b over-expression could reverse the protection of berberine in NIT-1 cells
      against from oxidative stress induced by high glucose. Berberine could attenuate
      oxidative stress of diabetic mice at least partly through miR-106b/SIRT1 pathway
      and affecting the function of islets, which might be beneficial in reducing the
      cardiovascular risk factors in diabetes. J. Cell. Biochem. 118: 4349-4357, 2017.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28436096
TI  - Urbanisation and the loss of phylogenetic diversity in birds.
AB  - Despite the recognised conservation value of phylogenetic diversity, little is
      known about how it is affected by the urbanisation process. Combining a complete
      avian phylogeny with surveys along urbanisation gradients from five continents,
      we show that highly urbanised environments supported on average 450 million fewer
      years of evolutionary history than the surrounding natural environments. This
      loss was primarily caused by species loss and could have been higher had not been
      partially compensated by the addition of urban exploiters and some exotic
      species. Highly urbanised environments also supported fewer evolutionary
      distinctive species, implying a disproportionate loss of evolutionary history.
      Compared with highly urbanised environments, changes in phylogenetic richness and
      evolutionary distinctiveness were less substantial in moderately urbanised
      environments. Protecting pristine environments is therefore essential for
      maintaining phylogenetic diversity, but moderate levels of urbanisation still
      preserve much of the original diversity.

PMID- 28436097
TI  - The vaginal microbiome and gynaecological cancer: exercise caution when
      considering causation.

PMID- 28436099
TI  - Review of nutrition guidelines relevant for adolescents in low- and middle-income
      countries.
AB  - The economic and social well-being of any country will one day depend on its
      current adolescent population. To provide a good foundation for healthy
      adolescent development, healthy diet, along with physical activity and adequate
      nutrients, is necessary. Therefore, addressing the nutrition needs of adolescents
      could be an important step toward breaking the vicious cycle of intergenerational
      malnutrition, chronic diseases, and poverty. These problems could be addressed
      with timely recognition and appropriately delivered interventions. Our aim here
      is to review the existing guidelines on various aspects of nutrition
      interventions for adolescents and young women. We review all of the major
      existing guidelines on adolescent nutrition. We were able to find 18 guideline
      bodies that covered some form of nutritional advice in guidelines that targeted
      adolescents. Although the guidelines that focus specifically on this age group
      are limited in scope, we also extrapolated recommendations from guidelines
      focused on adults, women of reproductive age, and pregnant women, which were
      based on evidence that included populations of adolescent girls. We were able to
      extract and synthesize specific directives for nutrition in adolescents, macro-
      and micronutrient supplementation, exercise, obesity, and nutrition during
      preconception, pregnancy, and the postconception period.

PMID- 28436098
TI  - LecRK-V, an L-type lectin receptor kinase in Haynaldia villosa, plays positive
      role in resistance to wheat powdery mildew.
AB  - Plant sense potential microbial pathogen using pattern recognition receptors
      (PRRs) to recognize pathogen-associated molecular patterns (PAMPs). The Lectin
      receptor-like kinase genes (LecRKs) are involved in various cellular processes
      mediated by signal transduction pathways. In the present study, an L-type lectin
      receptor kinase gene LecRK-V was cloned from Haynaldia villosa, a diploid wheat
      relative which is highly resistant to powdery mildew. The expression of LecRK-V
      was rapidly up-regulated by Bgt inoculation and chitin treatment. Its transcript
      level was higher in the leaves than in roots, culms, spikes and callus. Single
      cell transient overexpression of LecRK-V led to decreased haustorium index in
      wheat variety Yangmai158, which is powdery mildew susceptible. Stable
      transformation LecRK-V into Yangmai158 significantly enhanced the powdery mildew
      resistance at both seedling and adult stages. At seedling stage, the transgenic
      line was highly resistance to 18 of the tested 23 Bgt isolates, hypersensitive
      responses (HR) were observed for 22 Bgt isolates, and more ROS at the Bgt
      infection sites was accumulated. These indicated that LecRK-V confers broad
      spectrum resistance to powdery mildew, and ROS and SA pathways contribute to the
      enhanced powdery mildew resistance in wheat.

PMID- 28436100
TI  - Global and regional trends in the nutritional status of young people: a critical
      and neglected age group.
AB  - Adolescence and emerging adulthood form a critical time period for the
      achievement of optimal health and nutrition across all stages of the life course.
      We undertook a review of published literature and global data repositories for
      information on nutrition levels, trends, and patterns among young people aged 10
      24 years from January 1, 2016 to September 20, 2016. We describe patterns for
      both males and females at the global level and for geographic regions for the
      period covering 1990-2015. The results of this study paint a less than ideal
      picture of current young people's nutrition, suggesting dual burdens of
      underweight and high body-mass index in many countries and variable improvements
      in micronutrient deficiencies across geographical regions. Poor diet diversity
      and lack of nutrient-dense food, high risk for metabolic syndrome, and sedentary
      lifestyles also characterize this population. The need for objective, comparable,
      and high-quality data is also recognized for further study in this area. As the
      global community works toward supporting and scaling up health gains in the
      sustainable development goal era, realizing the critical role of young people is
      essential. Investing in young people's nutrition is critical to making strides in
      improving the overall health and well-being of all populations.

PMID- 28436101
TI  - Systematic review on evidence-based adolescent nutrition interventions.
AB  - Adolescence is a critical stage in the life cycle, and adequate nutrition is
      necessary for the proper growth and development of individuals and their
      offspring. Here, we comprehensively review all published systematic reviews
      (through October 2016) on adolescents (10-19 years) and women of reproductive
      age, including pregnant women, which targeted interventions related to nutrition.
      For interventions where there was no existing systematic review on adolescents,
      we reviewed primary studies/trials. We included interventions on micronutrient
      supplementation (iron, folic acid, iron-folic acid (IFA), calcium, vitamin D,
      vitamin A, zinc, iodine, and multiple micronutrients), food/protein energy
      supplementation, nutrition education for pregnant adolescents, obesity prevention
      and management, and management of gestational diabetes. We identified a total of
      35 systematic reviews, of which only five were conducted on adolescents, and 107
      primary studies on adolescents. Our review suggests that iron alone, IFA, zinc,
      and multiple micronutrient supplementation in adolescents can significantly
      improve serum hemoglobin concentration. While zinc supplementation in pregnant
      adolescents showed improvements in preterm birth and low birth weight, we found a
      paucity of trials on calcium, vitamin D, vitamin A, and iodine supplementation.
      We found limited evidence on food/protein energy supplementation in adolescents.
      Interventions to prevent and manage obesity showed a nonsignificant impact on
      reducing body mass index. This review underscores the importance of adolescent
      nutrition interventions. It is imperative that countries design nutritional
      interventions, particularly for adolescents.

PMID- 28436102
TI  - Nutrition in adolescents: physiology, metabolism, and nutritional needs.
AB  - Adolescence is the period of development that begins at puberty and ends in early
      adulthood. Most commonly, adolescence is divided into three developmental
      periods: early adolescence (10-14 years of age), late adolescence (15-19 years of
      age), and young adulthood (20-24 years of age). Adolescence is marked by physical
      and sexual maturation, social and economic independence, development of identity,
      acquisition of skills needed to carry out adult relationships and roles, and the
      capacity for abstract reasoning. Adolescence is characterized by a rapid pace of
      growth that is second only to that of infancy. Nutrition and the adolescent
      transition are closely intertwined, since eating patterns and behaviors are
      influenced by many factors, including peer influences, parental modeling, food
      availability, food preferences, cost, convenience, personal and cultural beliefs,
      mass media, and body image. Here, we describe the physiology, metabolism, and
      nutritional requirements for adolescents and pregnant adolescents, as well as
      nutrition-related behavior and current trends in adolescent nutrition. We
      conclude with thoughts on the implications for nutrition interventions and
      priority areas that would require further investigation.

PMID- 28436103
TI  - Delivering an action agenda for nutrition interventions addressing adolescent
      girls and young women: priorities for implementation and research.
AB  - Adolescent nutritional behaviors are assuming considerable importance in
      nutrition interventions given their important relationships with medium- and long
      term outcomes. This is the period when young people undergo major anatomical and
      physiological maturational changes in preparation for adulthood. Nutritional
      requirements during puberty are higher during adolescence than during the
      prepubertal stage and during adulthood. A significant proportion of adolescents
      also become parents, and hence the importance of their health and nutritional
      status before as well as during pregnancy has its impact on their own health,
      fetal well-being, and newborn health. In this paper, we describe the evidence
      based nutrition recommendations and the current global guidance for nutrition
      actions for adolescents. Despite the limitations of available information, we
      believe that a range of interventions are feasible to address outcomes in this
      age group, although some would need to start earlier in childhood. We propose
      packages of preventive care and management comprising nutrition-specific and
      nutrition-sensitive interventions to address adolescent undernutrition,
      overnutrition, and micronutrient deficiencies. We discuss potential delivery
      platforms and strategies relevant to low- and middle-income countries. Beyond the
      evidence synthesis, there is a clear need to translate evidence into policy and
      for implementation of key recommendations and addressing knowledge gaps through
      prioritized research.

PMID- 28436104
TI  - Corrigendum for Ann. N.Y. Acad. Sci. 1339: 176-189.

PMID- 28436106
TI  - Therapeutic plasma exchange as part of multimodal treatment of acquired
      hemophilia in a patient with concurrent acute intracerebral bleed and pulmonary
      embolism.
AB  - BACKGROUND: Autoantibodies against Factor VIII (FVIII) define the rare but life
      threatening bleeding disorder acquired hemophilia A (AHA). Correction of FVIII
      deficiency and eradication of the factor inhibitor are the ultimate therapeutic
      goals in this disorder. Bypassing agents such as recombinant factor VIIa (rFVIIa)
      or FVIII inhibitor bypassing agent are often used to control coagulopathy before
      the inhibitor is eradicated. Bypassing agents carry a risk of thrombosis,
      however. CASE REPORT: We report a patient with newly diagnosed AHA and thalamic
      bleed who additionally had active atrial fibrillation and developed a segmental
      pulmonary embolism, limiting tolerable rFVIIa dosage. This patient with very-high
      risk brain bleed and concurrent thrombosis on bypass agent represented a
      significant management dilemma for which we successfully utilized therapeutic
      plasma exchange (TPE) to reduce the inhibitor titer. RESULTS: FVIII inhibitor was
      undetectable and FVIII level was above the lower limit of normal within 12.5 days
      from starting TPE. While the patient ultimately died 24 days from admission for
      reasons unrelated to bleeding, his intracerebral hemorrhage was unchanged in size
      and no other bleeding morbidity was observed. CONCLUSION: This patient achieved
      eradication of FVIII inhibitor and did not have bleed expansion while receiving
      multimodal therapy including corticosteroids, rituximab, and TPE. We discuss the
      periprocedural risks of TPE in an acquired hemophilia patient and our multiteam
      management of that risk.

PMID- 28436105
TI  - Exercise Decreases Marrow Adipose Tissue Through beta-Oxidation in Obese Running
      Mice.
AB  - The relationship between marrow adipose tissue (MAT) and bone health is poorly
      understood. We used running exercise to ask whether obesity-associated MAT can be
      attenuated via exercise and whether this correlates with gains in bone quantity
      and quality. C57BL/6 mice were divided into diet-induced obesity (DIO, n = 14)
      versus low-fat diet (LFD, n = 14). After 3 months, 16-week-old mice were
      allocated to an exercise intervention (LFD-E, DIO-E) or a control group (LFD,
      DIO) for 6 weeks (4 groups, n = 7/group). Marrow adipocyte area was 44% higher
      with obesity (p < 0.0001) and after exercise 33% lower in LFD (p < 0.0001) and
      39% lower in DIO (p < 0.0001). In LFD, exercise did not affect adipocyte number;
      however, in DIO, the adipocyte number was 56% lower (p < 0.0001). MAT was 44%
      higher in DIO measured by osmium-MUCT, whereas exercise associated with reduced
      MAT (-23% in LFD, -48% in DIO, p < 0.05). MAT was additionally quantified by
      9.4TMRI, and correlated with osmium-uCT (r = 0.645; p < 0.01). Consistent with
      higher lipid beta oxidation, perilipin 3 (PLIN3) rose with exercise in tibial
      mRNA (+92% in LFD, +60% in DIO, p < 0.05). Tibial uCT-derived trabecular bone
      volume (BV/TV) was not influenced by DIO but responded to exercise with an
      increase of 19% (p < 0.001). DIO was associated with higher cortical periosteal
      and endosteal volumes of 15% (p = 0.012) and 35% (p < 0.01), respectively, but
      Ct.Ar/Tt.Ar was lower by 2.4% (p < 0.05). There was a trend for higher stiffness
      (N/m) in DIO, and exercise augmented this further. In conclusion, obesity
      associated with increases in marrow lipid-measured by osmium-MUCT and MRI-and
      partially due to an increase in adipocyte size, suggesting increased lipid uptake
      into preexisting adipocytes. Exercise associated with smaller adipocytes and less
      bone lipid, likely invoking increased beta-oxidation and basal lipolysis as
      evidenced by higher levels of PLIN3. (c) 2017 American Society for Bone and
      Mineral Research.

PMID- 28436109
TI  - Efficiency of Ustekinumab in Crohn's Disease with Severe Psoriasiform Rash
      Induced by Biotherapies in an Adolescent.
AB  - Ustekinumab is approved for the treatment of psoriasis in adolescents and for the
      treatment of moderate to severe Crohn's disease (CD) in adults, but data are
      lacking in pediatric CD. We report a case of severe psoriasis induced by
      biotherapies in an adolescent with CD that improved after switching to
      ustekinumab (90 mg at weeks 0, 2, and 4 and then every 8 weeks). The patient had
      not experienced CD relapse after 1 year of follow-up. Ustekinumab can be an
      alternative therapy for psoriasis induced by biotherapies when conventional
      treatment fails and can maintain remission of CD.

PMID- 28436107
TI  - A complete 4DCT-ventilation functional avoidance virtual trial: Developing
      strategies for prospective clinical trials.
AB  - INTRODUCTION: 4DCT-ventilation is an exciting new imaging modality that uses 4DCT
      data to calculate lung-function maps. Because 4DCTs are acquired as standard of
      care for lung cancer patients undergoing radiotherapy, 4DCT-ventiltation provides
      functional information at no extra dosimetric or monetary cost to the patient.
      The development of clinical trials is underway to use 4DCT-ventilation imaging to
      spare functional lung in patients undergoing radiotherapy. The purpose of this
      work was to perform a virtual trial using retrospective data to develop the
      practical aspects of a 4DCT-ventilation functional avoidance clinical trial.
      METHODS: The study included 96 stage III lung cancer patients. A 4DCT-ventilation
      map was calculated using the patient's 4DCT-imaging, deformable registration, and
      a density-change-based algorithm. Clinical trial inclusion assessment used
      quantitative and qualitative metrics based on the patient's spatial ventilation
      profile. Clinical and functional plans were generated for 25 patients. The
      functional plan aimed to reduce dose to functional lung while meeting standard
      target and critical structure constraints. Standard and dose-function metrics
      were compared between the clinical and functional plans. RESULTS: Our data showed
      that 69% and 59% of stage III patients have regional variability in function
      based on qualitative and quantitative metrics, respectively. Functional planning
      demonstrated an average reduction of 2.8 Gy (maximum 8.2 Gy) in the mean dose to
      functional lung. CONCLUSIONS: Our work demonstrated that 60-70% of stage III
      patients would be eligible for functional planning and that a typical functional
      lung mean dose reduction of 2.8 Gy can be expected relative to standard clinical
      plans. These findings provide salient data for the development of functional
      clinical trials.

PMID- 28436111
TI  - Early introduction of food reduces food allergy - Does it?

PMID- 28436112
TI  - Chiral Fidelity in the Diastereoselective and Enantiospecific Synthesis of
      Indenes from Axially Chiral Benzylidene Cyclanes.
AB  - Enantioenriched indenes were reached through a chirality conversion strategy
      using original axially chiral benzylidene cyclanes. Good to high remote
      diastereocontrol and excellent enantiocontrol were observed in this cascade
      involving copper-catalyzed homologation of terminal alkynes, in situ allenoate
      formation and Alder-ene cyclization.

PMID- 28436113
TI  - Using predictions from a joint model for longitudinal and survival data to inform
      the optimal time of intervention in an abdominal aortic aneurysm screening
      programme.
AB  - Joint models of longitudinal and survival data can be used to predict the risk of
      a future event occurring based on the evolution of an endogenous biomarker
      measured repeatedly over time. This has led naturally to the use of dynamic
      predictions that update each time a new longitudinal measurement is provided. In
      this paper, we show how such predictions can be utilised within a fuller decision
      modelling framework, in particular to allow planning of future interventions for
      patients under a 'watchful waiting' care pathway. Through the objective of
      maximising expected life-years, the predicted risks associated with not
      intervening (e.g. the occurrence of severe sequelae) are balanced against risks
      associated with the intervention (e.g. operative risks). Our example involves
      patients under surveillance in an abdominal aortic aneurysm screening programme
      where a joint longitudinal and survival model is used to associate longitudinal
      measurements of aortic diameter with the risk of aneurysm rupture. We illustrate
      how the decision to intervene, which is currently based on a diameter measurement
      greater than a certain threshold, could be made more personalised and dynamic
      through the application of a decision modelling approach.

PMID- 28436114
TI  - All-Trans-Retinoic Acid Stimulates Overexpression of Tumor Protein D52 (TPD52,
      Isoform 3) and Neuronal Differentiation of IMR-32 Cells.
AB  - Tumor protein D52 (TPD52), a proto-oncogene is overexpressed in a variety of
      epithelial carcinomas and plays an important role in cell proliferation,
      migration, and cell death. In the present study we found that the treatment of
      IMR-32 neuroblastoma (NB) cells with retinoic acid (RA) stimulates an increase in
      expression of TPD52. TPD52 expression is detectable after 72 h, can be maintained
      till differentiation of NB cells suggesting that TPD52 is involved in
      differentiation. Here, we demonstrate that TPD52 is essential for RA to promote
      differentiation of NB cells. Our results show that exogenous expression of EGFP
      TPD52 in IMR-32 cells resulted cell differentiation even without RA. RA by itself
      and with overexpression of TPD52 can increase the ability of NB cells
      differentiation. Interestingly, transfection of IMR-32 cells with a specific
      small hairpin RNA for efficient knockdown of TPD52 attenuated RA induced NB cells
      differentiation. Transcriptional and translational level expression of
      neurotropic (BDNF, NGF, Nestin) and differentiation (beta III tubulin, NSE, TH)
      factors in NB cells with altered TPD52 expression and/or RA treatment confirmed
      essential function of TPD52 in cellular differentiation. Furthermore, we show
      that TPD52 protects cells from apoptosis and arrest cell proliferation by varying
      expression of p27Kip1, activation of Akt and ERK1/2 thus promoting cell
      differentiation. Additionally, inhibition of STAT3 activation by its specific
      inhibitor arrested NB cells differentiation by EGFP-TPD52 overexpression with or
      without RA. Taken together, our data reveal that TPD52 act through activation of
      JAK/STAT signaling pathway to undertake NB cells differentiation induced by RA.
      J. Cell. Biochem. 118: 4358-4369, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436115
TI  - Genetic and environmental contributions to the association between ADHD and
      affective problems in early childhood-A Swedish population-based twin study.
AB  - Few twin studies have explored the relative contribution of genetic and
      environmental factors to the association between attention deficit hyperactivity
      disorder (ADHD) and affective problems, and no study has focused on preschool
      children. We used the classical twin design to explore the genetic and
      environmental overlap between ADHD symptoms and affective problems in preschool
      children, based on 879 five-year-old twin pairs born in Sweden 2004-2005.
      Questionnaire-based parent-ratings were used to measure ADHD symptoms and
      affective problems. A bivariate twin design was used to decompose variance in
      ADHD and affective problems into genetic and environmental components, and to
      test the degree to which these components overlapped across the two traits. Our
      results showed that there was a significant correlation of 0.34 (95% Confidence
      Interval [CI] 0.29-0.38) between ADHD and affective problems. This correlation
      was mostly explained by additive genetic factors (64%, 95%CI 37-93%), and to a
      lesser extent by shared environmental factors (35%, 95%CI 10-59%). Nonshared
      environmental factors did not contribute to the correlation between ADHD and
      affective problems (0%, 95%CI -9 to 10%). These findings show that there is a
      significant association between ADHD and affective problems in preschool children
      that is mostly explained by genetic influences. This adds important knowledge
      about the etiology of both ADHD and affective problems by indicating that these
      phenotypes are linked from as early as preschool years. This also needs to be
      taken into consideration when diagnosing young children and clinicians should
      consider assessing both affective problems and ADHD if one is present.

PMID- 28436116
TI  - Experiential learning about medication adherence.

PMID- 28436117
TI  - Early introduction of oral paricalcitol in renal transplant recipients. An open
      label randomized study.
AB  - In stable renal transplant recipients with hyperparathyroidism, previous studies
      have indicated that vitamin D agonist treatment might have anti-proteinuric
      effects. Animal studies indicate possible anti-fibrotic and anti-inflammatory
      effects. Early introduction of paricalcitol in de novo renal transplant
      recipients might reduce proteinuria and prevent progressive allograft fibrosis.
      We performed a single-center, prospective, randomized, open-label trial
      investigating effects of paricalcitol 2 MUg/day added to standard care.
      Participants were included 8 weeks after engraftment and followed for 44 weeks.
      Primary end point was change in spot urine albumin/creatinine ratio. Exploratory
      microarray analyses of kidney biopsies at study end investigated potential
      effects on gene expression. Secondary end points included change in glomerular
      filtration rate (GFR), pulse wave velocity (PWV), and endothelial function
      measured by peripheral arterial tonometry as reactive hyperemia index (RHI).
      Seventy-seven de novo transplanted kidney allograft recipients were included, 37
      receiving paricalcitol. Paricalcitol treatment lowered PTH levels (P = 0.01) but
      did not significantly reduce albuminuria (P = 0.76), change vascular parameters
      (PWV; P = 0.98, RHI; P = 0.33), or influence GFR (P = 0.57). Allograft gene
      expression was not influenced. To summarize, in newly transplanted renal
      allograft recipients, paricalcitol reduced PTH and was well tolerated without
      negatively affecting kidney function. Paricalcitol did not significantly
      reduce/prevent albuminuria, improve parameters of vascular health, or influence
      allograft gene expression.

PMID- 28436118
TI  - Enantioselective potential of polysaccharide-based chiral stationary phases in
      supercritical fluid chromatography.
AB  - The enantioselective potential of two polysaccharide-based chiral stationary
      phases for analysis of chiral structurally diverse biologically active compounds
      was evaluated in supercritical fluid chromatography using a set of 52 analytes.
      The chiral selectors immobilized on 2.5 MUm silica particles were tris-(3,5
      dimethylphenylcarmabate) derivatives of cellulose or amylose. The influence of
      the polysaccharide backbone, different organic modifiers, and different mobile
      phase additives on retention and enantioseparation was monitored. Conditions for
      fast baseline enantioseparation were found for the majority of the compounds. The
      success rate of baseline and partial enantioseparation with cellulose-based
      chiral stationary phase was 51.9% and 15.4%, respectively. Using amylose-based
      chiral stationary phase we obtained 76.9% of baseline enantioseparations and 9.6%
      of partial enantioseparations of the tested compounds. The best results on
      cellulose-based chiral stationary phase were achieved particularly with propane-2
      ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier
      and additive to CO2 , respectively. Methanol and basic additive isopropylamine
      were preferred on amylose-based chiral stationary phase. The complementary
      enantioselectivity of the cellulose- and amylose-based chiral stationary phases
      allows separation of the majority of the tested structurally different compounds.
      Separation systems were found to be directly applicable for analyses of
      biologically active compounds of interest.

PMID- 28436120
TI  - Efficacy of Holmium Laser Transurethral Incision of the Prostate in Symptomatic
      Mild-to-Moderate Benign Prostate Enlargement Based on Preoperative
      Characteristics.
AB  - OBJECTIVE: To investigate the efficacy of Holmium laser transurethral incision of
      the prostate (Ho-TUIP) with preoperative characteristics based on urodynamic
      parameters. METHODS: The medical records of 40 consecutive cases of Ho-TUIP in
      patients unresponsive to medical treatment were retrospectively reviewed. The
      efficacy of Ho-TUIP was analyzed according to preoperative factors, including
      urodynamic parameters. Treatment success was confirmed if overall efficacy
      demonstrated an improvement that was "good or greater" according to the criteria
      developed by Homma et al. Predictive factors of treatment success were analyzed
      using logistic regression analysis with demographics, symptom questionnaires,
      prostate size, and urodynamic parameters. Postoperative complications and Global
      Response Assessment (GRA) were investigated. RESULTS: Mean age was 60.9 years
      (range 37-84), mean follow-up period was 36.6 months (range 6.3-114.8), and mean
      prostate size was 23.5 mL (range 12.7-39.5). All patients underwent medical
      treatment before Ho-TUIP, and mean medication duration was 50.5 months (range 3.4
      140.0). The treatment success rate was 60.0%. Treatment success rates were higher
      in the bladder outlet obstruction index (BOOI) >=20 group (n = 26) than in the
      BOOI <20 group (n = 14) (p = 0.003). In logistic regression analysis, BOOI >=20
      was a predictor of treatment success (OR 7.60, 95% CI 1.60-35.90, P = 0.010).
      Among patients who maintained an active sex life, 77.8% (14/18) reported
      retrograde ejaculation. In terms of GRA, 81.5% (31/38, two patients expired) of
      patients improved at the final follow-up. CONCLUSIONS: Ho-TUIP is an effective
      procedure with tolerable complications for the treatment of symptomatic mild-to
      moderate BPE in patients with BOOI >=20 that are unresponsive to medical
      treatment.

PMID- 28436119
TI  - Maternal left ventricular hypertrophy and diastolic dysfunction and brain
      natriuretic peptide concentration in early- and late-onset pre-eclampsia.
AB  - OBJECTIVE: Pre-eclampsia (PE) is associated with maternal cardiac remodeling and
      diastolic dysfunction. The aim of this study was to assess and compare maternal
      left ventricular structure and diastolic function and levels of brain natriuretic
      peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with
      late-onset (>= 34 weeks' gestation) PE. METHODS: This was a prospective, cross
      sectional, observational study of 30 women with early-onset PE, 32 with late
      onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic
      function were assessed by echocardiography and plasma levels of BNP were measured
      by enzyme immunoassay. RESULTS: Early- and late-onset PE were associated with
      increased left ventricular mass index and relative wall thickness compared with
      normotensive controls. In women with early-onset PE, the prevalence of concentric
      hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher
      (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal
      serum BNP levels were significantly higher (P < 0.05) in women with early-onset
      PE and correlated with relative wall thickness and left ventricular mass index.
      CONCLUSIONS: Early-onset PE is associated with more severe cardiac impairment
      than is late-onset PE, as evidenced by an increased prevalence of concentric
      hypertrophy, diastolic dysfunction and higher levels of BNP. These findings
      suggest that early-onset PE causes greater myocardial damage, increasing the risk
      of both peripartum and postpartum cardiovascular morbidity. Although these
      cardiovascular effects are easily identified by echocardiographic parameters and
      measuring BNP, further studies are needed to assess their clinical utility.
      Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28436121
TI  - 10-Silacorroles Exhibiting Near-Infrared Absorption and Emission.
AB  - 10-Silacorroles were obtained from the Pd-catalyzed silylative cyclization of a
      bis(alpha,alpha'-dibromodipyrrin) NiII precursor with dihydrosilanes. These 10
      silacorroles show substantially red-shifted absorption bands relative to those of
      normal porphyrins and isocorroles. Notably, the corresponding free base and ZnII 
      10-silacorroles exhibit emissions in the NIR region. Theoretical calculations on
      these 10-silacorroles revealed the presence of sigma*-pi* conjugation between the
      silyl group and the tetrapyrrole pi system, which significantly lowers their LUMO
      energy levels.

PMID- 28436122
TI  - Metabolic engineering of Escherichia coli for production of 2-Phenylethylacetate
      from L-phenylalanine.
AB  - In order to meet the need of consumer preferences for natural flavor compounds,
      microbial synthesis method has become a very attractive alternative to the
      chemical production. The 2-phenylethanol (2-PE) and its ester 2
      phenylethylacetate (2-PEAc) are two extremely important flavor compounds with a
      rose-like odor. In recent years, Escherichia coli and yeast have been
      metabolically engineered to produce 2-PE. However, a metabolic engineering
      approach for 2-PEAc production is rare. Here, we designed and expressed a 2-PEAc
      biosynthetic pathway in E. coli. This pathway comprised four steps:
      aminotransferase (ARO8) for transamination of L-phenylalanine to phenylpyruvate,
      2-keto acid decarboxylase KDC for the decarboxylation of the phenylpyruvate to
      phenylacetaldehyde, aldehyde reductase YjgB for the reduction of
      phenylacetaldehyde to 2-PE, alcohol acetyltransferase ATF1 for the esterification
      of 2-PE to 2-PEAc. Using the engineered E. coli strain for shake flasks
      cultivation with 1 g/L L-phenylalanine, we achieved co-production of 268 mg/L 2
      PEAc and 277 mg/L 2-PE. Our results suggest that approximately 65% of L
      phenylalanine was utilized toward 2-PEAc and 2-PE biosynthesis and thus
      demonstrate potential industrial applicability of this microbial platform.

PMID- 28436123
TI  - An improved uniformly more powerful exact Fisher-Hayter pairwise comparisons
      procedure.
AB  - Pairwise comparison is a very common multiple comparison problem. It is known
      that Fisher's LSD test does not control the familywise error rate (FWER) when
      there are more than three groups to be compared. Improved testing strategies
      include the Tukey-Kramer (TK) test that eliminates the F-test step and the two
      step Fisher-Hayter (FH) test which requires a significant F-test. We propose a
      modified FH-test that is uniformly more powerful than the original version and
      relies on exact size alpha test under the balanced model. We provide simulations
      to show that the new procedure is preferred to the FH-test and the TK-test.

PMID- 28436124
TI  - Characteristics and respiratory risk profile of children aged less than 5 years
      presenting to an urban, Aboriginal-friendly, comprehensive primary health
      practice in Australia.
AB  - AIM: There are no published data on factors impacting on acute respiratory
      illness (ARI) among urban Indigenous children. We describe the characteristics
      and respiratory risk profile of young urban Indigenous children attending an
      Aboriginal-friendly primary health-care practice. METHODS: We conducted a cross
      sectional analysis of data collected at baseline in a cohort study investigating
      ARI in urban Indigenous children aged less than 5 years registered with an
      Aboriginal primary health-care service. Descriptive analyses of epidemiological,
      clinical, environmental and cultural factors were performed. Logistic regression
      was undertaken to examine associations between child characteristics and the
      presence of ARI at baseline. RESULTS: Between February 2013 and October 2015, 180
      Indigenous children were enrolled; the median age was 18.4 months (7.7-35), 51%
      were male. A total of 40 (22%) children presented for a cough-related illness;
      however, ARI was identified in 33% of all children at the time of enrolment. A
      total of 72% of children were exposed to environmental tobacco smoke. ARI at
      baseline was associated with low birthweight (adjusted odds ratio (aOR) 2.54, 95%
      confidence interval (CI) 1.08-5.94), a history of eczema (aOR 2.67, 95% CI 1.00
      7.15) and either having a family member from the Stolen Generation (aOR 3.47, 95%
      CI 1.33-9.03) or not knowing this family history (aOR 3.35, 95% CI 1.21-9.26).
      CONCLUSIONS: We identified an urban community of children of high socio-economic
      disadvantage and who have excessive exposure to environmental tobacco smoke.
      Connection to the Stolen Generation or not knowing the family history may be
      directly impacting on child health in this community. Further research is needed
      to understand the relationship between cultural factors and ARI.

PMID- 28436125
TI  - The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm
      labor.
AB  - OBJECTIVE: To evaluate the impact of triaging women at risk of spontaneous
      preterm birth (sPTB) using the QUiPP App, which incorporates a predictive model
      combining history of sPTB, gestational age and quantitative measurements of fetal
      fibronectin, compared with a treat-all policy (advocated by the UK National
      Institute for Health and Care Excellence) among women with threatened preterm
      labor before 30 weeks' gestation. METHODS: Prospectively collected data of
      pregnant women presenting with symptoms of preterm labor (abdominal pain or
      tightening) at 24-34 weeks' gestation were retrieved from the research databases
      of the EQUIPP and PETRA studies for subanalysis. Each episode of threatened
      preterm labor was retrospectively assigned a risk for sPTB within 7 days using
      the QUiPP App. A primary outcome of delivery within 7 days was used to model the
      performance accuracy of the QUiPP App compared with a treat-all policy. RESULTS:
      Using a 5% risk of delivery within 7 days according to the QUiPP App as the
      threshold for intervention, 9/9 women who presented with threatened preterm labor
      < 34 weeks would have been treated correctly, giving a sensitivity of 100% (one
      sided 97.5% CI, 66.4%) and a negative predictive value of 100% (97.5% CI, 98.9
      100%). The positive predictive value for delivery within 7 days was 30.0% (95%
      CI, 11.9-54.3%) for women presenting before 30 weeks and 20.0% (95% CI, 12.7
      30.1%) for women presenting between 30 + 0 and 34 + 0 weeks. If this 5% threshold
      had been used to triage women presenting between 24 + 0 and 29 + 6 weeks, 89.4%
      (n = 168) of admissions could have been safely avoided, compared with 0% for a
      treat-all strategy. No true case of preterm labor would have been missed, as no
      woman who was assigned a risk of < 10% delivered within 7 days. CONCLUSION: For
      women with threatened preterm labor, the QUiPP App can accurately guide
      management at risk thresholds for sPTB of 1%, 5% and 10%, allowing outpatient
      management in the vast majority of cases. A treat-all approach would not have
      avoided admission for any woman, and would have exposed 188 mothers and their
      babies to unnecessary hospitalization and steroid administration and increased
      the burden on network and transport services owing to unnecessary in-utero
      transfers. Prediction of sPTB should be performed before 30 weeks to determine
      management until there is evidence that such a high level of unnecessary
      intervention, as suggested by the treat-all strategy, does less harm than the
      occurrence of rare false negatives. Copyright (c) 2017 ISUOG. Published by John
      Wiley & Sons Ltd.

PMID- 28436126
TI  - Gast Editorial: Celebrating Canadian Chemistry.
AB  - "... This issue of Angewandte Chemie commemorates the 100th anniversary of the
      Canadian Society for Chemistry. It contains contributions from Canadian and
      German chemists covering a broad and diverse array of subject areas. We are proud
      to reflect on the accomplishments of the Canadian chemical community and are
      excited about what the future holds ...".

PMID- 28436127
TI  - Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving
      Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2.
AB  - HIV-1 Tat-interacting protein of 110 kDa, Tip110, plays important roles in
      multiple biological processes. In this study, we aimed to characterize the
      function of Tip110 in embryonic development. Transgenic mice lacking expression
      of a functional Tip110 gene (Tip110-/- ) died post-implantation, and Tip110-/-
      embryos exhibited developmental arrest between 8.5 and 9.5 days post coitum.
      However, in vitro cultures of Tip110-/- embryos showed that Tip110 loss did not
      impair embryo growth from the zygote to the blastocyst. Extended in vitro
      cultures of Tip110-/- blastocysts showed that Tip110 loss impaired both
      blastocyst outgrowth and self-renewal and survival of blastocyst-derived
      embryonic stem cells. Microarray analysis of Tip110-/- embryonic stem cells
      revealed that Tip110 loss altered differentiation, pluripotency, and cycling of
      embryonic stem cells and was associated with downregulation of several major stem
      cell factors including Nanog, Oct4, and Sox2 through a complex network of
      signaling pathways. Taken together, these findings document for the first time
      the lethal effects of complete loss of Tip110 on mammalian embryonic development
      and suggest that Tip110 is an important regulator of not only embryonic
      development but also stem cell factors. Stem Cells 2017;35:1674-1686.

PMID- 28436128
TI  - Transrectal high-intensity focused ultrasound as focal therapy for posterior deep
      infiltrating endometriosis.

PMID- 28436129
TI  - Use of an electronic brachytherapy surface applicator to treat an epiglottal
      fibrosarcoma in a dog.
AB  - Presented is the case of an epiglottal fibrosarcoma in a dog. The location of the
      mass resulted in challenges in the delivery of adequate dose to the tumor, and
      herein we describe the treatment using an electronic brachytherapy source. The
      treatment consisted of four Gy fractions, twice daily for a total of 10 fractions
      (40 Gy total). Visual reevaluation two weeks after treatment supported adequate
      spatial dose delivery, and the patient was reportedly improved six weeks after
      treatment. We demonstrate that plesiotherapy using an electronic brachytherapy
      device is feasible and may be useful in the treatment of carefully selected
      veterinary tumors.

PMID- 28436130
TI  - Sleep complaints associated with wish to die after a suicide crisis-an
      exploratory study.
AB  - The present study explores whether sleep concerns are associated with wish to die
      throughout a 1-month time interval following a suicide crisis. Sixty-eight
      patients admitted to the emergency department of a general or psychiatric
      hospital were enrolled. Sleep difficulties were assessed using the Insomnia
      Severity Index (ISI), the Epworth Sleepiness Scale, self-reported satisfaction
      with sleep and time in bed. Suicidal ideation was assessed through the presence
      of a wish to die at 1 month following a suicide crisis. Co-existing psychiatric
      diagnoses were assessed using the French version of the Mini International
      Neuropsychiatric Interview (MINI). Potential covariate factors such as personal
      and family history of suicidal behaviours and sociodemographic variables were
      accounted for. We found that wish to die was associated significantly with
      insomnia severity, low satisfaction with sleep and sleep duration 1 month after
      the suicide crisis, even after controlling for covariates. This exploratory study
      is limited by a small sample size, and results cannot be generalized to patients
      with psychotic disorders or alcohol use disorders. Also, other factors related
      potentially to suicidal ideation, such as depression severity, stressful events
      or levels of family support, were not accounted for. However, overall our study
      supports the assessment of sleep complaints as a potential indicator of suicide
      risk in the weeks that follow a suicide crisis.

PMID- 28436131
TI  - Twisting of Alkynes towards a Carbon Double Helix.
AB  - The carbon allotrope exhibiting only one-dimensional sp-hybridized carbon atoms
      is called carbyne. However, its existence is very controversial. Studies on model
      compounds for carbyne revealed that many oligoalkynes show not a straight, but a
      bent structure of the carbon chain. Here, we question whether it would also be
      possible to obtain a more complex structure from carbyne, such as a dimeric
      double helix. Based on quantum chemical calculations, we show that only a small
      energetic expense is needed for the formation of a double helix starting from
      oligoalkyne chains. In some cases, the double helix-like conformation is more
      stable than the corresponding conformation with a parallel arrangement of the
      acetylene chains. Furthermore, model systems were synthesized in which two
      diphenyl oligoalkyne chains are fixed and twisted by a chiral imidazole
      containing clamp. A structural investigation of these model systems was performed
      based on UV and CD spectroscopy and quantum chemical calculations. The observed
      twisting in these model systems can be regarded as the first small step towards
      an imaginable carbon double helix.

PMID- 28436132
TI  - Selective Aerobic Oxidation of Methylarenes to Benzaldehydes Catalyzed by N
      Hydroxyphthalimide and Cobalt(II) Acetate in Hexafluoropropan-2-ol.
AB  - Efficient and highly selective catalytic conditions for the aerobic autoxidation
      of methylarenes to benzaldehydes, based on N-hydroxyphthalimide (NHPI) and
      cobalt(II) acetate in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP), were developed.
      The sustainable conditions enable a multigram scale preparation of benzaldehyde
      derivatives in high efficiency and with excellent chemoselectivity (up to 99 %
      conversion and 98 % selectivity).

PMID- 28436133
TI  - Population trends in prenatal detection of transposition of great arteries:
      impact of obstetric screening ultrasound guidelines.
AB  - OBJECTIVES: Dextro-transposition of the great arteries (d-TGA) is one of the most
      common critical neonatal heart defects, with a low detection rate antenatally. We
      sought to evaluate trends in the prenatal detection of d-TGA with or without
      ventricular septal defect (VSD) in Alberta over the past 13 years, examining the
      potential impact of ultrasound guidelines incorporating screening of cardiac
      outflow tracts, updated in 2009-2010 and in 2013, and factors affecting detection
      of the condition. METHODS: All fetuses and neonates with d-TGA, with or without
      VSD, encountered between 2003 and 2015 in the province of Alberta, were
      identified retrospectively. Clinical records including obstetric ultrasound
      reports were reviewed. Pregnancy outcome, common referral indications and
      associated maternal and fetal pathology in affected pregnancies were assessed.
      RESULTS: From 2003 to 2015, 127 cases with d-TGA were encountered in Alberta, of
      which 47 (37%) were detected prenatally. Prenatal detection improved over the
      study period, from 14% in 2003-2010, to 50% in 2011-2013, and to 77% in 2014
      2015. Of the 47 fetuses with a prenatal diagnosis of d-TGA, an indication for
      fetal echocardiography included abnormal or poorly visualized cardiac outflows
      with normal four-chamber view in 46 (98%). Comorbidities were identified in 12
      mothers, only five of which represented an additional reason for fetal
      echocardiography referral, and four fetuses had extracardiac pathology.
      CONCLUSION: Substantial improvement in the prenatal detection of d-TGA has been
      observed in Alberta over the past few years, owing to improved screening of
      cardiac outflow tracts on routine obstetric ultrasound examination in otherwise
      healthy pregnancies, and has been temporally associated with updated obstetric
      ultrasound guidelines suggesting that these contributed to optimized screening of
      affected pregnancies. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons
      Ltd.

PMID- 28436134
TI  - Measurement of skin surface dose distributions in radiation therapy using
      poly(vinyl alcohol) cryogel dosimeters.
AB  - In external beam radiation therapy (EBRT), skin dose measurement is important to
      evaluate dose coverage of superficial target volumes. Treatment planning systems
      (TPSs) are often inaccurate in this region of the patient, so in vivo
      measurements are necessary for skin surface dose estimation. In this work,
      superficial dose distributions were measured using radiochromic translucent
      poly(vinyl alcohol) cryogels. The cryogels simultaneously served as bolus
      material, providing the necessary buildup to achieve the desired superficial
      dose. The relationship between dose to the skin surface and dose measured with
      the bolus was established using a series of oblique irradiations with gantry
      angles ranging from 0 degrees  to 90 degrees . EBT-2 Gafchromic film was placed
      under the bolus, and the ratio of bolus-film dose was determined ranging from
      0.749 +/- 0.005 to 0.930 +/- 0.002 for 0 degrees  and 90 degrees  gantry angles,
      respectively. The average ratio over 0-67.5 degrees  (0.800 +/- 0.064) was used
      as the single correction factor to convert dose in bolus to dose to the skin
      surface. The correction factor was applied to bolus measurements of skin dose
      from head and neck intensity-modulated radiation therapy (IMRT) treatments
      delivered to a RANDO phantom. The resulting dose distributions were compared to
      film measurements using gamma analysis with a 3%/3 mm tolerance and a 10%
      threshold. The minimum gamma pass rate was 95.2% suggesting that the radiochromic
      bolus may provide an accurate estimation of skin surface dose using a simple
      correction factor. This study demonstrates the suitability of radiochromic
      cryogels for superficial dose measurements in megavoltage photon beams.

PMID- 28436135
TI  - Psychiatric medication use before and after the onset of type 1 diabetes in
      children and adolescents: A population-based cohort study.
AB  - BACKGROUND: Several studies showed a bidirectional association between type 2
      diabetes and psychiatric disorders in adults. Because there is limited
      information on the association between type 1 diabetes (T1D) and psychiatric
      disorders (including psychiatric medication use) in children and adolescents, we
      assessed frequency of use of these medications before and after the onset of T1D.
      METHODS: A population-based cohort study was conducted in the Dutch PHARMO Record
      Linkage System (1999-2009). Children and adolescents (<19 years) with at least 2
      insulin dispensings from community pharmacies (T1D cohort, N = 925) were matched
      by age and sex (reference cohort without insulin use, N = 3591). The 5-year
      prevalence of psychiatric medication use (psycholeptics [ATC N05] and
      psychoanaleptics [ATC N06]) before and after onset of T1D were estimated,
      compared, and stratified by age, sex, and medication subgroup. RESULTS: The mean
      age of study participants was 10.1 years and 51% were boys. The 5-year prevalence
      of psychiatric medication use before the index date was significantly higher in
      the T1D cohort than in the reference cohort (7.2% vs 4.7%, respectively; P =
      .002) with the same pattern after developing T1D (10.4% vs 7.9%, respectively; P
      = .015). In both cohorts, adolescents (15-19 years) and boys had higher
      prevalences of use. This increased prevalence of psychiatric medication use both
      before and after the index date in T1D cohort was mainly driven by an increased
      use of psycholeptics (predominantly anxiolytics). CONCLUSIONS: Children with T1D
      were more likely to use psychiatric medication in the years before and after the
      onset of T1D which was mainly driven by psycholeptic use.

PMID- 28436136
TI  - Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron
      deficient heart failure patients: an individual patient data meta-analysis.
AB  - AIMS: Iron deficiency (ID) is a common co-morbidity in patients with heart
      failure (HF) and has been suggested to be associated with poor prognosis.
      Recently completed double-blind randomised controlled trials (RCTs) studying HF
      patients with ID have shown improvements in functional capacity, symptoms and
      quality of life when treated with i.v. ferric carboxymaltose (FCM). This
      individual patient data meta-analysis investigates the effect of FCM vs. placebo
      on recurrent hospitalisations and mortality in HF patients with ID. METHODS AND
      RESULTS: Individual patient data were extracted from four RCTs comparing FCM with
      placebo in patients with systolic HF and ID. The main outcome measures were
      recurrent cardiovascular (CV) hospitalisations and CV mortality. Other outcomes
      included cause-specific hospitalisations and death. The main analyses of
      recurrent events were backed up by time-to-first-event analyses. In total, 839
      patients, of whom 504 were randomised to FCM, were included. Compared with those
      taking placebo, patients on FCM had lower rates of recurrent CV hospitalisations
      and CV mortality [rate ratio 0.59, 95% confidence interval (CI) 0.40-0.88; P =
      0.009]. Treatment with FCM also reduced recurrent HF hospitalisations and CV
      mortality (rate ratio 0.53, 95% CI 0.33-0.86; P = 0.011) and recurrent CV
      hospitalisations and all-cause mortality (rate ratio 0.60, 95% CI 0.41-0.88; P =
      0.009). Time-to-first-event analyses showed similar findings, with somewhat
      attenuated treatment effects. The administration of i.v. FCM was not associated
      with an increased risk for adverse events. CONCLUSIONS: Treatment with i.v. FCM
      was associated with a reduction in recurrent CV hospitalisations in systolic HF
      patients with ID.

PMID- 28436137
TI  - Insights into in vitro spermatogenesis in mammals: Past, present, future.
AB  - Considering the self-renewal and differentiation ability of pluripotent stem
      cells, some studies have pointed out the possibility of stem cell-derived sperm
      production. Most studies that test this hypothesis have been conducted on
      rodents, with some promising results; however, studies on humans are progressing
      slowly, and have encountered technical and ethical hurdles. Established methods
      to differentiate stem cells-including embryoid bodies, co-culturing, and various
      feeder cells-may provide a niche that is similar to in vivo conditions and
      resolve epigenetic abnormalities, but a gonadal-like three-dimensional structure
      is still required to produce germ cells with the correct imprinting. In the last
      few years, sperm-like cells with fertilizing capacity were produced from mouse
      embryonic stem cells, and the resulting embryos from these cells yielded live
      offspring. Future research should move towards the use of adult stem cells,
      however, owing to the unavailability of embryonic cells in adults. More intensive
      research and techniques are required since in vitro spermatogenesis provides hope
      to individuals without mature sperm who cannot be treated, and may be a useful
      system to study the precise mechanism of spermatogenesis. In this review, we
      describe recent studies of in vitro spermatogenesis mechanisms and related
      techniques in mammals. We also discuss the possible cell surface markers and
      culture conditions that might improve in vitro spermatogenesis.

PMID- 28436138
TI  - Predictors of health-related quality of life among industrial workers: A
      descriptive correlational study.
AB  - Assessment and evaluation of the health-related quality of life of industrial
      workers is an important research focus. This descriptive correlational study
      identifies the predictors of health-related quality of life using a random
      sampling of industrial workers (n = 640) from construction factories in Amman
      Governorate in Jordan using demographic characteristics, a health and work
      related factors questionnaire, and the World Health Organization Quality of Life
      Brief scale. Results showed that industrial workers had good physical health but
      a poor working environment. There was a statistically significant relationship
      between educational level, conflict between work and individual life and work and
      social life, working hours, and workload, and all domains of health-related
      quality of life. Overall, educational level was the main predictor for all
      domains of health-related quality of life. Such results confirm the need to
      develop appropriate interventions and strategies to improve workers' health
      related quality of life. Furthermore, developing an integrated approach among
      policymakers, employers, and work organizations to enhance industrial workers'
      occupational health programs could be effective.

PMID- 28436139
TI  - Improving scope sensitivity in contingent valuation: Joint and separate
      evaluation of health states.
AB  - We present data of a contingent valuation survey, testing the effect of
      evaluation mode on the monetary valuation of preventing road accidents. Half of
      the interviewees was asked to state their willingness to pay (WTP) to reduce the
      risk of having only 1 type of injury (separate evaluation, SE), and the other
      half of the sample was asked to state their WTP for 4 types of injuries evaluated
      simultaneously (joint evaluation, JE). In the SE group, we observed lack of
      sensitivity to scope while in the JE group WTP increased with the severity of the
      injury prevented. However, WTP values in this group were subject to context
      effects. Our results suggest that the traditional explanation of the disparity
      between SE and JE, namely, the so-called "evaluability," does not apply here. The
      paper presents new explanations based on the role of preference imprecision.

PMID- 28436140
TI  - High-Pressure Synthesis of Fully Occupied Tetragonal and Cubic Tungsten Bronze
      Oxides.
AB  - A high-pressure reaction yielded the fully occupied tetragonal tungsten bronze K3
      W5 O15 (K0.6 WO3 ). The terminal phase shows an unusual transport property
      featuring slightly negative temperature-dependence in resistivity (drho/dT<0) and
      a large Wilson ratio of RW =3.2. Such anomalous metallic behavior possibly arises
      from the low-dimensional electronic structure with a van Hove singularity at the
      Fermi level and/or from enhanced magnetic fluctuations by geometrical frustration
      of the tungsten sublattice. The asymmetric nature of the tetragonal tungsten
      bronze Kx WO3 -K0.6-y Bay WO3 phase diagram implies that superconductivity for
      x<=0.45 originates from the lattice instability because of potassium deficiency.
      A cubic perovskite KWO3 phase was also identified as a line phase-in marked
      contrast to Nax WO3 and Lix WO3 with varying quantities of x (<1). This study
      presents a versatile method by which the solubility limit of tungsten bronze
      oxides can be extended.

PMID- 28436141
TI  - MicroRNA-10b regulates the renewal of spermatogonial stem cells through Kruppel
      like factor 4.
AB  - MicroRNAs (miRs) are functionally important in spermatogenesis, which is the self
      renewal or differentiation of spermatogonial stem cells (SSCs). Here, we report a
      novel role for miR-10b in regulating the self-renewal of mouse SSCs. We showed
      that miR-10b was highly expressed in mouse SSCs in vitro and enhanced SSC
      proliferation. Knockdown of miR-10b significantly increased the apoptosis of SSCs
      compared with controls. Kruppel-like factor 4 was found to be a target gene of
      miR-10b in the enhancement of SSC proliferation. These findings further our
      understanding of the self-renewal and differentiation of SSCs and provide a basis
      for the diagnosis, treatment, and prevention of male infertility.

PMID- 28436142
TI  - Cortisol is associated with low frequency of interleukin 10-producing B cells in
      patients with atherosclerosis.
AB  - It is accepted that inflammation plays a critical role in the development of
      atherosclerosis; the pathogenesis is not clear. B-cell-produced interleukin (IL)
      10 is an immune regulatory cytokine that can inhibit immune inflammation. This
      study tests a hypothesis that a psychological stress hormone, cortisol,
      suppresses IL-10 expression in peripheral B cells of patients with
      atherosclerosis. Peripheral blood samples were collected from patients with
      coronary artery atherosclerosis. B cells were isolated from the blood samples to
      be analyzed for the expression of IL-10 and micro RNA (miR) 98 by real-time
      polymerase chain reaction. We observed that the frequency of IL-10+ B cell was
      less in patients with atherosclerosis than healthy controls. The serum cortisol
      levels were higher in the patients than that in healthy controls. Peripheral B
      cell frequency was negatively correlated with the serum cortisol levels. Exposure
      of B cells to cortisol increased the expression of miR-98 in B cells. Cortisol
      also inhibited the expression of IL-10 in B cells, in which miR-98 played a
      critical role. Treating B cells from atherosclerosis patients with anti-miR-98
      liposomes reversed the ability of expression of IL-10 in the cells. The
      expression of IL-10 is suppressed in peripheral B cells, which can be up
      regulated by anti-miR-98 liposomes.

PMID- 28436143
TI  - Corrigendum: Strain- and time-dependent alterations in hepatic iron metabolism in
      a murine model of nonalcoholic steatohepatitis.

PMID- 28436144
TI  - Unacylated Ghrelin Enhances Satellite Cell Function and Relieves the Dystrophic
      Phenotype in Duchenne Muscular Dystrophy mdx Model.
AB  - Muscle regeneration depends on satellite cells (SCs), quiescent precursors that,
      in consequence of injury or in pathological states such as muscular dystrophies,
      activate, proliferate, and differentiate to repair the damaged tissue. A subset
      of SCs undergoes self-renewal, thus preserving the SC pool and its regenerative
      potential. Unacylated ghrelin (UnAG) is a circulating hormone that protects
      muscle from atrophy, promotes myoblast differentiation, and enhances ischemia
      induced muscle regeneration. Here we show that UnAG increases SC activity and
      stimulates Par polarity complex/p38-mediated asymmetric division, fostering both
      SC self-renewal and myoblast differentiation. Because of those activities on
      different steps of muscle regeneration, we hypothesized a beneficial effect of
      UnAG in mdx dystrophic mice, in which the absence of dystrophin leads to chronic
      muscle degeneration, defective muscle regeneration, fibrosis, and, at later
      stages of the pathology, SC pool exhaustion. Upregulation of UnAG levels in mdx
      mice reduces muscle degeneration, improves muscle function, and increases
      dystrophin-null SC self-renewal, maintaining the SC pool. Our results suggest
      that UnAG has significant therapeutic potential for preserving the muscles in
      dystrophies. Stem Cells 2017;35:1733-1746.

PMID- 28436145
TI  - Comparisons of the Clinical Outcomes and Urodynamic Effects of Mirabegron versus
      Tolterodine Treatment for Female Overactive Bladder Syndrome: A Subgroup Analysis
      of a Controlled, Randomised, Prospective Study.
AB  - OBJECTIVES: The impact of mirabegron on clinical outcome and urodynamic
      parameters may be important for clinical practice. Thus, the aim of this study
      was to compare the clinical outcomes and urodynamic effects of mirabegron
      (Betmiga 50 mg) versus tolterodine (Detrusitol ER 4 mg) treatment for women with
      overactive bladder syndrome (OAB). METHODS: Women with OAB were randomized to
      receive 12 weeks of mirabegron 50 mg, tolterodine extended-release 4 mg or
      placebo treatment. The clinical outcomes and urodynamic effects were compared
      between the subgroups. RESULTS: Thirty-three women completed 12 weeks of
      mirabegron (n = 12), tolterodine (n = 12) or placebo (n = 9) treatment. A
      significant increase in the volumes at strong desire to void and a decrease in
      the daytime frequency episodes were identified in the mirabegron and tolterodine
      groups (all P < 0.05). Nonetheless, a decrease in the total voided volume was
      identified following mirabegron treatment but not tolterodine (P = 0.02).
      CONCLUSIONS: Mirabegron and tolterodine exhibit similar changes in the
      urodynamics and bladder diary parameters. However, mirabegron may decrease the
      total voided volume. These findings may serve as an initial guide or assist in
      consultations regarding the treatment of OAB patients with mirabegron.

PMID- 28436146
TI  - Improving zinc accumulation in cereal endosperm using HvMTP1, a transition metal
      transporter.
AB  - Zinc (Zn) is essential for all life forms, including humans. It is estimated that
      around two billion people are deficient in their Zn intake. Human dietary Zn
      intake relies heavily on plants, which in many developing countries consists
      mainly of cereals. The inner part of cereal grain, the endosperm, is the part
      that is eaten after milling but contains only a quarter of the total grain Zn.
      Here, we present results demonstrating that endosperm Zn content can be enhanced
      through expression of a transporter responsible for vacuolar Zn accumulation in
      cereals. The barley (Hordeum vulgare) vacuolar Zn transporter HvMTP1 was
      expressed under the control of the endosperm-specific D-hordein promoter.
      Transformed plants exhibited no significant change in growth but had higher total
      grain Zn concentration, as measured by ICP-OES, compared to parental controls.
      Compared with Zn, transformants had smaller increases in concentrations of Cu and
      Mn but not Fe. Staining grain cross sections with the Zn-specific stain DTZ
      revealed a significant enhancement of Zn accumulation in the endosperm of two of
      three transformed lines, a result confirmed by ICP-OES in the endosperm of
      dissected grain. Synchrotron X-ray fluorescence analysis of longitudinal grain
      sections demonstrated a redistribution of grain Zn from aleurone to endosperm. We
      argue that this proof-of-principle study provides the basis of a strategy for
      biofortification of cereal endosperm with Zn.

PMID- 28436147
TI  - Rapid detection of six phosphodiesterase type 5 enzyme inhibitors in healthcare
      products using thin-layer chromatography and surface enhanced Raman spectroscopy
      combined with BP neural network.
AB  - A novel facile method for the detection of the phosphodiesterase type 5 enzyme
      inhibitors added illegally into health products was established using thin-layer
      chromatography and surface enhanced Raman spectroscopy combined with BP neural
      network. When the detection conditions were optimized in detail, a repetitive
      adding procedure of silver colloids with the total amount keeping constant was
      used to improve the enhancement effect of surface enhanced Raman spectroscopy.
      According to the main Raman peaks and the retention factor of analyte, the data
      predictive model was established. Under the optimized experimental conditions,
      this method was successful to apply to detect the artificially produced model
      samples, and the limit of detection less than 5 mg/kg was obtained. Based on the
      excellent sensitivity of this method, the real samples have been detected
      accurately and the detection results were confirmed by high-performance liquid
      chromatography. In addition, the developed method was suitable for the detection
      of other adulterants, especially those that have similar chromatographic or
      spectroscopic behaviors.

PMID- 28436148
TI  - Relationship between self-assessment and clinical evaluation of dental plaque and
      gingival condition in Japanese adolescents.
AB  - OBJECTIVES: To apply a self-administered assessment form about dental plaque
      level and gingival condition to Japanese adolescents and to examine the extent to
      which they can evaluate their own dental plaque and gingivae by comparing with
      dentists' clinical evaluation. METHODS: Participants were 151 senior high school
      students (adolescents) who observed their own mouths and recorded dental plaque
      seen on their 12 anterior teeth, and gingival inflammation condition of 10
      anterior interdental papillae, on a self-assessment form. Dentists clinically
      evaluated dental plaque using the, modified Debris Index (modified DI) and
      gingival condition, modified PMA index (P-index). "Recognition score" of dental
      plaque and gingival condition was the total number of agreement between the
      adolescents' self-assessment and dentists' evaluation. RESULTS: Proportion of
      agreement on dental plaque between the adolescents' self-assessment and dentists'
      evaluation with modified DI was 37.4%, and agreement on modified DI score 1, 2 or
      3 was significantly lower than that on score 0 (P<.01). Agreement on gingivae was
      47.3% in total, and agreement was significantly lower on gingival condition with
      inflammation than gingivae without inflammation (P<.01). Recognition scores of
      dental plaque or gingival condition were significantly lower in adolescents with
      fair or poor modified DI or P-index than in those with good condition (P<.01).
      CONCLUSION: Most adolescents could not recognize their dental plaque and gingival
      condition. Adolescents with poorer dental plaque level or gingival condition had
      lower recognition scores compared to those with better oral health. Improving
      oral health self-assessment skills could help adolescents achieve better oral
      health.

PMID- 28436150
TI  - George A. Olah (1927-2017).

PMID- 28436149
TI  - Transgenic miR156 switchgrass in the field: growth, recalcitrance and rust
      susceptibility.
AB  - Sustainable utilization of lignocellulosic perennial grass feedstocks will be
      enabled by high biomass production and optimized cell wall chemistry for
      efficient conversion into biofuels. MicroRNAs are regulatory elements that
      modulate the expression of genes involved in various biological functions in
      plants, including growth and development. In greenhouse studies, overexpressing a
      microRNA (miR156) gene in switchgrass had dramatic effects on plant architecture
      and flowering, which appeared to be driven by transgene expression levels. High
      expressing lines were extremely dwarfed, whereas low and moderate-expressing
      lines had higher biomass yields, improved sugar release and delayed flowering.
      Four lines with moderate or low miR156 overexpression from the prior greenhouse
      study were selected for a field experiment to assess the relationship between
      miR156 expression and biomass production over three years. We also analysed
      important bioenergy feedstock traits such as flowering, disease resistance, cell
      wall chemistry and biofuel production. Phenotypes of the transgenic lines were
      inconsistent between the greenhouse and the field as well as among different
      field growing seasons. One low expressing transgenic line consistently produced
      more biomass (25%-56%) than the control across all three seasons, which
      translated to the production of 30% more biofuel per plant during the final
      season. The other three transgenic lines produced less biomass than the control
      by the final season, and the two lines with moderate expression levels also
      exhibited altered disease susceptibilities. Results of this study emphasize the
      importance of performing multiyear field studies for plants with altered
      regulatory transgenes that target plant growth and development.

PMID- 28436152
TI  - Multispecialty involvement in the management of type B aortic dissections in the
      endovascular era-Implications for training cardiothoracic residents.
AB  - PURPOSE: Involvement of qualified specialists with proficiency in endovascular
      therapies has created flux regarding the role of cardiothoracic surgeons,
      vascular surgeons, and other catheter-skilled specialists in the management of
      type B aortic dissections. We used manuscript authorship trends and recent match
      data in order to study how multi-specialty involvement in treating aortic
      dissections has changed in the endovascular era. METHODS: A PubMed review of
      published literature between 1998 and 2015 was performed with "aortic dissection"
      in the title. Case studies and entries with incomplete author or identifying
      information were excluded. Author number, specialty affiliation, and treatment
      focus were recorded. Available residency match data were obtained from the
      National Resident Matching Program (NRMP). RESULTS: Cardiothoracic surgeons
      represented 38.5% (10/23) of the authors for papers with an endovascular focus in
      1998 compared with 27.7% (59/213) in 2015. Vascular surgeons represented 19.2%
      (5/23) and 37.1% (79/213) of authors in 1998 and 2015, respectively. Radiologists
      accounted for 30.4% (7/23) of authorship in 1998 and 8.9% (19/213) in 2015. NRMP
      match data revealed a 10.6% decrease in thoracic surgery matches from 2004 to
      2015, while vascular surgery and interventional radiology increased by 74.7% and
      191.1%, respectively. CONCLUSIONS: Endovascular technologies have resulted in
      significant changes as to which specialties manage complicated type B aortic
      dissections. Vascular surgeons, with both open and extensive endovascular
      training are optimally positioned to assume a major role in the care of aortic
      dissection patients. Continued emphasis on endovascular training and
      multispecialty collaboration is essential for cardiothoracic surgeons in the
      endovascular era.

PMID- 28436153
TI  - Reliability and Validity of the Persian Language Version of the International
      Consultation on Incontinence Questionnaire - Male Lower Urinary Tract Symptoms
      (ICIQ-MLUTS).
AB  - OBJECTIVES: Assessment instruments are essential for research, allowing diagnosis
      and evaluating treatment outcomes in subjects with lower urinary tract disorders
      of both genders. The purpose of this study was to translate the Male Lower
      Urinary Tract Symptoms (MLUTS) Questionnaire and determine its psychometric
      properties in Persian subjects. METHODS: After getting permission from the
      International Consultation on Incontinence Modular Questionnaire (ICIQ) web site,
      the forward and backward translation of the MLUTS questionnaire were carried out
      by researcher team. The content/face validity, construct validity and reliability
      were assessed in a sample of MLUTS Iranian patients by measuring with the
      Cronbach's alpha test. RESULTS: In total, 121 male patients were included in the
      study. The mean age of the patients was 60.5 years. Cronbach alpha value was
      0.757, consecrated the internal consistency of the form (r > 0.7). The internal
      consistency of each question was examined separately and found to be over 0.7.
      For the evaluation of reliability test-retest was done, the test was administered
      to 20% of the patients for a second time with an interval of 1-2 weeks. The
      intraclass correlation coefficient (ICC) score was 0.901. The Correlation
      coefficient between the MLUTS and International Prostate Symptoms Score (IPSS)
      was 0.879. CONCLUSIONS: ICIQ-MLUTS is a robust instrument, which can be used for
      evaluating male LUTS in Persian patients. We believe that the Persian version of
      the MLUTS is an important tool for research and clinical setting.

PMID- 28436154
TI  - Effects of a simple home-based exercise program on fall prevention in older
      adults: A 12-month primary care setting, randomized controlled trial.
AB  - AIM: To investigate the effects of a simple home-based exercise program on falls,
      physical functioning, fear of falling and quality of life in a primary care
      setting. METHODS: Participants (n = 439), aged >=65 years with mild-to-moderate
      balance dysfunction were randomly assigned to an exercise (n = 219) or control (n
      = 220) group. The program consisted of five combined exercises, which progressed
      in difficulty, and a walking plan. Controls received fall prevention education.
      Physical functioning and other outcomes were measured at 3- and 6-month follow-up
      visits. Falls were monitored with fall diaries and phone interviews at 3, 6, 9,
      and 12 months respectively. RESULTS: The 12 months of the home-based exercise
      program showed the incidence of falls was 0.30 falls per person year in the
      exercise group, compared with 0.40 in the control group. The estimated incidence
      rate ratio was 0.75 (95% CI 0.55-1.04), which was not statistically significant.
      The fear of falling (measured by the Thai fall efficacy scale) was significantly
      lower in the exercise than control group (24.7 vs 27.0, P = 0.003). Also, the
      trend of program adherence increased in the exercise group. (29.6% to 56.8%).
      CONCLUSIONS: This simple home-based exercise program showed a reduction in fear
      of falling and a positive trend towards exercise adherence. Further studies
      should focus on factors associated with exercise adherence, the benefits of
      increased home visits and should follow participants longer in order to evaluate
      the effects of the program. Geriatr Gerontol Int 2017; 17: 2157-2163.

PMID- 28436151
TI  - Whole genome sequence association and ancestry-informed polygenic profile of EEG
      alpha in a Native American population.
AB  - EEG alpha activity is the dominant oscillation in most adult humans, is highly
      heritable, and has been associated with a number of cognitive functions. Two EEG
      phenotypes, low- and high-voltage alpha (LVA & HVA), have been demonstrated to
      have high heritabilities. They have different prevalence depending on a
      population's ancestral origins. In the present study we assessed the influence of
      ancestry admixture on EEG alpha power, and conducted a whole genome sequencing
      association analysis and an ancestry-informed polygenic study on those phenotypes
      in a Native American (NA) population that has a high prevalence of LVA. Seven
      common variants, in LD with each other upstream from gene ASIC2, reached genome
      wide significance (p = 2 * 10-8 ) having a positive association with alpha
      voltage. They had lower minor allele frequencies in the NAs than in a global
      population sample. Overall correlations between lower degrees of NA (higher
      degree European) ancestry and HVA, and higher degrees of NA and LVA were also
      found. Additionally a rare-variant gene-based study identified gene TIA1 being
      negatively associated with LVA. Approximately 3% of SNPs exhibited a 15-fold
      enrichment that explained nearly half of the total SNP-heritability for EEG
      alpha. These regions showed the most significant anti-correlations between NA
      ancestry and alpha voltage, and were enriched for genes and pathways mediating
      cognitive functions. Our findings suggested that these regions likely harbor
      causal variants for HVA, and lacking of such variants could explain the high
      prevalence of LVA in this NA population, possibly illuminating the ancestral
      origin and genetic basis for EEG alpha.

PMID- 28436156
TI  - Faculty development effects on clerkship grades.
AB  - BACKGROUND: Faculty member assessment of clerkship students' clinical performance
      has been noted as a consistently problematic issue within most medical student
      clerkships, and thus a worthy target of faculty development. One of the primary
      challenges in such faculty development is creating a change that improves the
      clinical assessment of students in a meaningful way. METHOD: In the current study
      we evaluated the effects of a pair of brief interventions designed to facilitate
      greater use of the 'Not observed' option in faculty member assessments of
      clerkship students (as opposed to use of 'Meets expectations' for skills actually
      not observed by the rater) within a psychiatry rotation for third-year medical
      students in the USA. RESULTS: The intervention demonstrated statistically
      significant effects, both intentional and unintentional. Specifically, faculty
      members rated themselves as having increased their own understanding and
      confidence regarding the use of the assessment forms after the intervention. With
      regard to actual ratings of clerkship students, faculty members were less likely
      to use the 'Not observed' option after the intervention. Also, the mean rating
      increased slightly, and to a greater degree than could be explained entirely by
      the shift away from using 'Meets expectations' when 'Not observed' was more
      appropriate. Faculty member assessment of ... students' clinical performance [is]
      a consistently problematic issue DISCUSSION: Results are discussed with regards
      to suggestions for implementation of the intervention in other programmes,
      specifically with regard to proposed improvements and issues to consider and
      monitor.

PMID- 28436155
TI  - The Mobius AIRO mobile CT for image-guided proton therapy: Characterization &
      commissioning.
AB  - PURPOSE: The purpose of this study was to characterize the Mobius AIRO Mobile CT
      System for localization and image-guided proton therapy. This is the first known
      application of the AIRO for proton therapy. METHODS: Five CT images of a
      Catphan(r) 504 phantom were acquired on the AIRO Mobile CT System, Varian EDGE
      radiosurgery system cone beam CT (CBCT), Philips Brilliance Big Bore 16 slice CT
      simulator, and Siemens SOMATOM Definition AS 20 slice CT simulator. DoseLAB
      software v.6.6 was utilized for image quality analysis. Modulation transfer
      function, scaling discrepancy, geometric distortion, spatial resolution, overall
      uniformity, minimum uniformity, contrast, high CNR, and maximum HU deviation were
      acquired. Low CNR was acquired manually using the CTP515 module. Localization
      accuracy and CT Dose Index were measured and compared to reported values on each
      imaging device. For treatment delivery systems (Edge and Mevion), the
      localization accuracy of the 3D imaging systems were compared to 2D imaging
      systems on each system. RESULTS: The AIRO spatial resolution was 0.21 lp mm-1
      compared with 0.40 lp mm-1 for the Philips CT Simulator, 0.37 lp mm-1 for the
      Edge CBCT, and 0.35 lp mm-1 for the Siemens CT Simulator. AIRO/Siemens and
      AIRO/Philips differences exceeded 100% for scaling discrepancy (191.2% and
      145.8%). The AIRO exhibited higher dose (>27 mGy) than the Philips CT Simulator.
      Localization accuracy (based on the MIMI phantom) was 0.6 degrees  and 0.5 mm.
      Localization accuracy (based on Stereophan) demonstrated maximum AIRO-kV/kV shift
      differences of 0.1 mm in the x-direction, 0.1 mm in the y-direction, and 0.2 mm
      in the z-direction. CONCLUSIONS: The localization accuracy of AIRO was determined
      to be within 0.6 degrees  and 0.5 mm despite its slightly lower image quality
      overall compared to other CT imaging systems at our institution. Based on our
      study, the Mobile AIRO CT system can be utilized accurately and reliably for
      image-guided proton therapy.

PMID- 28436157
TI  - Real-time teleophthalmology video consultation: an analysis of patient
      satisfaction in rural Western Australia.
AB  - BACKGROUND: Teleophthalmology, particularly real-time video consultation, holds
      great potential in Australia and similar countries worldwide, where geography,
      population and medical workforce distribution make it difficult to provide
      specialist eye services outside of major cities. Assessment and referrals from
      rural optometrists are vital to the success of teleophthalmology. While there is
      good evidence for the efficacy of such services, there is limited evidence for
      patient satisfaction with video consultation. METHODS: To evaluate patient
      satisfaction with teleophthalmology, the current study recruited patients who
      underwent a video consultation with Lions Outback Vision, for a follow-up
      telephone-based questionnaire assessing satisfaction. Regression analysis was
      performed assessing which demographic features and which features of the video
      consultation itself were associated with highest overall satisfaction. RESULTS:
      One hundred and nine of the 137 eligible patients completed the questionnaire
      (79.6 per cent; 55 per cent male; mean age 64.61 years). The majority of the
      participants were either 'Very satisfied' (69.1 per cent) or 'Satisfied' (24.5
      per cent) with the service. No one reported being either 'Dissatisfied' or 'Very
      dissatisfied'. Linear regression did not reveal any demographic or follow-up
      variables as predictive of greater total satisfaction; however, participants who
      were older, felt they could easily explain their medical problems to the doctor
      in the video consultation and believed that telemedicine enabled them to save
      money and time, and were more likely to report higher overall satisfaction.
      CONCLUSION: Teleophthalmology is a promising new way to overcome barriers to the
      delivery of eye care services to rural and remote populations. This study
      demonstrates a high level of overall satisfaction with teleophthalmological video
      consultation and patients are accepting of this emerging consultation modality,
      regardless of age.

PMID- 28436158
TI  - Collaborating on medication errors in nursing.
AB  - BACKGROUND: Nurse educators are faced with changing roles and expanding
      responsibilities for medication administration and monitoring in pursuit of
      improved patient safety. The aims of this study were to develop, implement and
      evaluate clinical simulation experiences that included, along with nursing
      faculty members, a pharmacist educator for the teaching of preventable medication
      errors in undergraduate nursing education. METHODS: Four clinical simulation
      scenarios using high-fidelity patient simulators were developed focusing on
      select medication problems in nursing practice. Post-simulation evaluation of
      perceptions and experiences of undergraduate nursing students (n = 69) were
      assessed using a questionnaire of Likert-type items, including: (1) an evaluation
      of the simulation experience; and (2) self-reported perceived benefits for
      clinical ability and confidence in recognising, managing and reporting medication
      errors. RESULTS: Four hospital-based simulations on select preventable medication
      errors were piloted with 72 undergraduate nursing students. The majority of
      students (60.8-84.1%) evaluated the experience positively with regards to time
      pressure, type/severity of events, challenges, and benefits for critical thinking
      and decision making regarding patient safety and medication errors. Four clinical
      simulation scenarios using high-fidelity patient simulators were developed
      focusing on select medication problems DISCUSSION: The use of a pharmacy educator
      as a medication expert and member of the interprofessional health care teaching
      team in nursing education can be beneficial for training on medication safety,
      and on adverse effects, in a nursing programme in order to enhance nursing
      students' education.

PMID- 28436160
TI  - Compound heterozygous mutations in COL1A1 associated with an atypical form of
      type I osteogenesis imperfecta.
AB  - Heterozygous mutations in the genes encoding the proalpha1(I) or proalpha2(I)
      chains of type I procollagen (COL1A1 and COL1A2, respectively) account for most
      cases of osteogenesis imperfecta (OI), a disorder characterized by reduced bone
      strength and increased fracture risk. COL1A1 mutations can also cause rare cases
      of Ehlers-Danlos syndrome (EDS), a disorder that primarily affects connective
      tissue and often includes reduced bone mass. Here we present a kindred of three
      young siblings ages 1-4 years old whose mother has a history of mild type I OI.
      All three children are compound heterozygotes for COL1A1 mutations, with a novel
      frameshift mutation (c.2522delC; p.Pro841Leufs*266) from their mother and a known
      missense mutation (c.3196C>T; p.R1066C) from their clinically unaffected father,
      which has previously been described as causing a combined type I OI/EDS
      phenotype. The three children exhibit features of both COL1A1 mutations: early
      and frequent long bone fractures, joint hyperextensibility, and blue sclerae. We
      describe three siblings who are the first reported surviving subjects with
      biallelic pathogenic COL1A1 mutations. They have a more severe form of type I OI
      with features of EDS that represents their compound heterozygosity for two
      deleterious COL1A1 mutations. Their long-term outcomes are yet to be determined.

PMID- 28436159
TI  - Modulation of late sodium current by Ca2+ -calmodulin-dependent protein kinase
      II, protein kinase C and Ca2+ during hypoxia in rabbit ventricular myocytes.
AB  - NEW FINDINGS: What is the central question of this study? Hypoxia-induced
      increase in late sodium current (INa,L ) is associated with conditions causing
      cellular Ca2+ overload and contributes to arrhythmogenesis in the ventricular
      myocardium. The INa,L is an important drug target. We investigated intracellular
      signal transduction pathways involved in modulation of INa,L during hypoxia. What
      is the main finding and its importance? Hypoxia caused increases in INa,L ,
      reverse Na+ -Ca2+ exchange current and diastolic [Ca2+ ], which were attenuated
      by inhibitors of Ca2+ -calmodulin-dependent protein kinase II (CaMKII) and
      protein kinase C and by a Ca2+ chelator. The findings suggest that CaMKII,
      protein kinase C and Ca2+ all participate in mediation of the effect of hypoxia
      to increase INa,L . Hypoxia leads to augmentation of the late sodium current
      (INa,L ) and cellular Na+ loading, increased reverse Na+ -Ca2+ exchange current
      (reverse INCX ) and intracellular Ca2+ loading in rabbit ventricular myocytes.
      The purpose of this study was to determine the intracellular signal transduction
      pathways involved in the modulation of INa,L during hypoxia in ventricular
      myocytes. Whole-cell and cell-attached patch-clamp techniques were used to record
      INa,L , and the whole-cell mode was also used to record reverse INCX and to study
      intercellular signal transduction mechanisms that mediate the increased INa,L .
      Dual excitation fluorescence photomultiplier systems were used to record the
      calcium transient in ventricular myocytes. Hypoxia caused increases of INa,L and
      reverse INCX . These increases were attenuated by KN-93 (an inhibitor of Ca2+ 
      calmodulin-dependent protein kinase II), bisindolylmaleimide VI (BIM; an
      inhibitor of protein kinase C) and BAPTA AM (a Ca2+ chelator). KN-93, BIM and
      BAPTA AM had no effect on INa,L in normoxia. In studies of KN-93, hypoxia alone
      increased the density of INa,L from -0.31 +/- 0.02 to -0.66 +/- 0.03 pA pF-1 (n =
      6, P < 0.01 versus control) and the density of reverse INCX from 1.02 +/- 0.06 to
      1.91 +/- 0.20 pA pF-1 (n = 7, P < 0.01 versus control) in rabbit ventricular
      myocytes. In the presence of 1 MUm KN-93, the densities of INa,L and reverse INCX
      during hypoxia were significantly attenuated to -0.44 +/- 0.03 (n = 6, P < 0.01
      versus hypoxia) and 1.36 +/- 0.15 pA pF-1 (n = 7, P < 0.01 versus hypoxia),
      respectively. In studies of BIM, hypoxia increased INa,L from -0.30 +/- 0.03 to 
      0.60 +/- 0.03 pA pF-1 (n = 6, P < 0.01 versus control) and reverse INCX from 0.91
      +/- 0.10 to 1.71 +/- 0.27 pA pF-1 (n = 6, P < 0.01 versus control). In the
      presence of 1 MUm BIM, the densities of INa,L and reverse INCX during hypoxia
      were significantly attenuated to -0.48 +/- 0.02 (n = 6, P < 0.01 versus hypoxia)
      and 1.33 +/- 0.21 pA pF-1 (n = 6, P < 0.01 versus hypoxia), respectively. In
      studies of BAPTA AM, hypoxia increased INa,L from -0.26 +/- 0.04 to -0.63 +/-
      0.05 pA pF-1 (n = 6, P < 0.01 versus control) and reverse INCX from 0.86 +/- 0.09
      to 1.68 +/- 0.35 pA pF-1 (n = 6, P < 0.01 versus control). The effects of hypoxia
      on INa,L and reverse INCX were significantly attenuated in the presence of 1 mm
      BAPTA AM to -0.39 +/- 0.02 (n = 6, P < 0.01 versus hypoxia) and 1.12 +/- 0.27 pA
      pF-1 (n = 6, P < 0.01 versus hypoxia), respectively. Results of single-channel
      studies showed that hypoxia apparently increased the mean open probability and
      mean open time of sodium channels. These effects were inhibited by either 1 MUm
      KN-93 or 1 mm BAPTA AM. The suppressant effects of drug interventions were
      reversed upon washout. In addition, KN-93, BIM and BAPTA AM also reversed the
      hypoxia-enhanced diastolic Ca2+ concentration and the attenuated amplitude of the
      [Ca2+ ]i transient, maximal velocities of Ca2+ increase and Ca2+ decay. In
      summary, the findings suggest that Ca2+ -calmodulin-dependent protein kinase II,
      protein kinase C and Ca2+ all participate in mediation of the effect of hypoxia
      to increase INa,L .

PMID- 28436161
TI  - Dispersive liquid-liquid microextraction as an effective preanalytical step for
      the determination of estradiol in human urine.
AB  - In this work, a fast and effective dispersive liquid-liquid microextraction was
      developed for the isolation and preconcentration of free 17 beta-estradiol, the
      main human estrogen, from real human urine samples. To optimize the extraction
      technique, few important parameters such as type and volume of extraction and
      dispersive solvents, centrifugation conditions, effect of salt addition, and
      extraction time were studied. Optimal conditions were obtained when injecting 600
      MUL mixture of tetrachloromethane as extraction solvent and ethanol as dispersive
      solvent (1:5, v/v) into 2 mL of urine containing 8% NaCl and following
      centrifugation at 10 000 rpm, thus reaching enrichment factor 28 and extraction
      recovery 98% for estradiol. Procedure was evaluated by means of high-performance
      liquid chromatography with UV detection (lambda = 280 nm) using a C-18 column and
      methanol/water (60:40, v/v) as the mobile phase. The method was linear within the
      concentration range 1.0-250.0 mg/L (r = 0.9997) and provided a limit of detection
      of 0.25 mg/L. The proposed method was applied to the determination of free
      estradiol in real human pregnancy urine.

PMID- 28436162
TI  - The path forward: 2015 International Children's Tumor Foundation conference on
      neurofibromatosis type 1, type 2, and schwannomatosis.
AB  - The Annual Children's Tumor Foundation International Neurofibromatosis Meeting is
      the premier venue for connecting discovery, translational and clinical scientists
      who are focused on neurofibromatosis types 1 and 2 (NF1 and NF2) and
      schwannomatosis (SWN). The meeting also features rare tumors such as glioma,
      meningioma, sarcoma, and neuroblastoma that occur both within these syndromes and
      spontaneously; associated with somatic mutations in NF1, NF2, and SWN. The
      meeting addresses both state of the field for current clinical care as well as
      emerging preclinical models fueling discovery of new therapeutic targets and
      discovery science initiatives investigating mechanisms of tumorigenesis.
      Importantly, this conference is a forum for presenting work in progress and
      bringing together all stakeholders in the scientific community. A highlight of
      the conference was the involvement of scientists from the pharmaceutical industry
      who presented growing efforts for rare disease therapeutic development in general
      and specifically, in pediatric patients with rare tumor syndromes. Another
      highlight was the focus on new investigators who presented new data about
      biomarker discovery, tumor pathogenesis, and diagnostic tools for NF1, NF2, and
      SWN. This report summarizes the themes of the meeting and a synthesis of the
      scientific discoveries presented at the conference in order to make the larger
      research community aware of progress in the neurofibromatoses.

PMID- 28436163
TI  - Social defeat models in animal science: What we have learned from rodent models.
AB  - Studies on stress and its impacts on animals are very important in many fields of
      science, including animal science, because various stresses influence animal
      production and animal welfare. In particular, the social stresses within animal
      groups have profound impact on animals, with the potential to induce abnormal
      behaviors and health problems. In humans, social stress induces several health
      problems, including psychiatric disorders. In animal stress models, social defeat
      models are well characterized and used in various research fields, particularly
      in studies concerning mental disorders. Recently, we have focused on behavior,
      nutrition and metabolism in rodent models of social defeat to elucidate how
      social stresses affect animals. In this review, recent significant progress in
      studies related to animal social defeat models are described. In the field of
      animal science, these stress models may contribute to advances in the development
      of functional foods and in the management of animal welfare.

PMID- 28436164
TI  - Synthesis and SAR Study of Anticancer Protoflavone Derivatives: Investigation of
      Cytotoxicity and Interaction with ABCB1 and ABCG2 Multidrug Efflux Transporters.
AB  - There is a constant need for new therapies against multidrug-resistant (MDR)
      cancer. Natural compounds are a promising source of novel anticancer agents. We
      recently showed that protoflavones display activity in MDR cancer cell lines that
      overexpress the P-glycoprotein (P-gp) drug efflux pump. In this study, 52
      protoflavones, including 22 new derivatives, were synthesized and tested against
      a panel of drug-sensitive parental cells and their MDR derivatives obtained by
      transfection with the human ABCB1 or ABCG2 genes, or by adaptation to
      chemotherapeutics. With the exception of protoapigenone, identified as a weak
      ABCG2 substrate, all protoflavones bypass resistance conferred by these two
      transporters. The majority of the compounds were found to exhibit mild to strong
      (up to 13-fold) selectivity against the MCF-7Dox and KB-V1 cell lines, but not to
      transfected MDR cells engineered to overexpress the MDR transporters. Our results
      suggest that protoflavones can overcome MDR cancer by evading P-gp-mediated
      efflux.

PMID- 28436165
TI  - Production of high concentration of l-lactic acid from oil palm empty fruit bunch
      by thermophilic Bacillus coagulans JI12.
AB  - Thermophilic Bacillus coagulans JI12 was used to ferment hemicellulose
      hydrolysate obtained by acid hydrolysis of oil palm empty fruit bunch at 50 
      degrees C and pH 6, producing 105.4 g/L of l-lactic acid with a productivity of
      9.3 g/L/H by fed-batch fermentation under unsterilized conditions. Simultaneous
      saccharification and fermentation (SSF) was performed at pH 5.5 and 50  degrees C
      to convert both hemicellulose hydrolysate and cellulose-lignin complex in the
      presence of Cellic Ctec2 cellulases using yeast extract (20 g/L) as the nitrogen
      source, giving 114.0 g/L of l-lactic acid with a productivity of 5.7 g/L/H. The
      SSF was also conducted by replacing yeast extract with equal amount of dry
      Bakers' yeast, achieving 120.0 g/L of l-lactic acid with a productivity of 4.3
      g/L/H. To the best of our knowledge, these lactic acid titers and productivities
      are the highest ever reported from lignocellulose hydrolysates.

PMID- 28436166
TI  - Perinatal loss at term: role of uteroplacental and fetal Doppler assessment.
AB  - OBJECTIVE: To examine the associations of uterine artery (UtA) Doppler indices
      and cerebroplacental ratio (CPR) with perinatal outcome at term. METHODS: This
      was a retrospective cohort study conducted at a tertiary referral center that
      included all singleton pregnancies undergoing ultrasound assessment in the third
      trimester that subsequently delivered at term. Fetal biometry and Doppler
      assessment, including that of the umbilical artery (UA), fetal middle cerebral
      artery (MCA) and UtA, were recorded. Data were corrected for gestational age, and
      CPR was calculated as the ratio of MCA pulsatility index (PI) to UA-PI. Logistic
      regression analysis was conducted to examine for independent predictors of
      adverse perinatal outcome. RESULTS: The study included 7013 pregnancies, 12 of
      which were complicated by perinatal death. When compared with pregnancies
      resulting in perinatal survival, pregnancies complicated by perinatal death had a
      significantly higher proportion of small-for-gestational-age infants (25.0% vs
      5%; P = 0.001) and a higher incidence of low (< 5th centile) CPR (16.7% vs 4.5%;
      P = 0.041). A subgroup analysis comparing 1527 low-risk pregnancies that resulted
      in fetal survival with pregnancies complicated by perinatal death demonstrated
      that UtA-PI multiples of the median (MoM), CPR < 5th centile and estimated fetal
      weight (EFW) centile were all associated significantly with the risk of perinatal
      death at term (all P < 0.05). After adjusting for confounding variables, only EFW
      centile (odds ratio (OR) 0.96 (95% CI, 0.93-0.99); P = 0.003) and UtA-PI MoM (OR
      13.10 (95%CI, 1.95-87.89); P = 0.008) remained independent predictors of
      perinatal death in the low-risk cohort. CONCLUSION: High UtA-PI at term is
      associated independently with an increased risk of adverse perinatal outcome,
      regardless of fetal size. These results suggest that perinatal mortality at term
      is related not only to EFW and fetal redistribution (CPR), but also to indices of
      uterine perfusion. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28436167
TI  - Placental histopathology associated with pre-eclampsia: systematic review and
      meta-analysis.
AB  - OBJECTIVE: Pre-eclampsia (PE) is associated with impaired trophoblastic invasion
      and typical villous and vascular placental lesions. The primary aim of this study
      was to quantify the prevalence of placental histopathological lesions in
      pregnancies complicated by PE. METHODS: MEDLINE, EMBASE and CINAHL were searched
      electronically, and relevant articles reporting on placental histopathological
      lesions were assessed according to the following criteria: study design, number
      of pregnancies included, severity of PE and whether the pathologist was blinded
      to the clinical information. Prospective and retrospective case-control studies
      including >= 100 pregnancies were included in the systematic review. The
      incidence of each type of histological lesion according to the Perinatal Section
      of the Society for Pediatric Pathology classification in pre-eclamptic and normal
      pregnancies was identified, and lesions were categorized into two main groups:
      villous lesions and vascular lesions. Random-effects meta-analysis of proportions
      was used for analysis. Between-study heterogeneity was assessed using the I2
      statistic. RESULTS: The search yielded 717 citations, and a total of eight
      studies (four blinded and four non-blinded) were included in the review. In
      unblinded studies, the pooled prevalence of villous lesions was 11.6% and 48.2%
      in normal and pre-eclamptic pregnancies, respectively, giving a pooled odds ratio
      (OR) of 7.59. In blinded studies, the pooled prevalence of villous lesions was
      18.5% and 42.0% in normal and pre-eclamptic pregnancies, respectively, giving a
      pooled OR of 4.28. In unblinded studies, the pooled prevalence of vascular
      lesions was 8.1% and 37.3% in normal and pre-eclamptic pregnancies, respectively,
      giving a pooled OR of 20.34. In blinded studies, the pooled prevalence of
      vascular lesions was 9.8% and 38.9%, in normal and pre-eclamptic pregnancies,
      respectively, giving a pooled OR of 7.08. CONCLUSIONS: In blinded studies, the
      incidence of both placental villous and vascular histopathological lesions is
      four- to seven-fold higher in pre-eclamptic than in normal pregnancies. Greater
      differences are reported in unblinded studies. Despite the higher probability
      (point prevalence) of finding abnormal placental pathology in pregnancies with
      PE, placental lesions are not specific to the diagnosis of PE. Copyright (c) 2017
      ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28436168
TI  - Effects of nitrogen fertilizer and harvesting stage on photosynthetic pigments
      and phytol contents of Italian ryegrass silage.
AB  - This study aimed to investigate the effects of nitrogen (N) fertilizer
      application and harvesting stage on the contents of chlorophyll, phytol and
      carotenoids (beta-carotene and lutein) in Italian ryegrass herbage before and
      after ensiling, and the extent of phytol preservation after ensiling. Three rates
      of N fertilizer (0, 60 and 120 kg N/ha) were applied by top-dressing as an
      additional fertilizer. The herbage harvested at booting stage (27 weeks of age)
      or heading stage (29 weeks of age) were wilted for 1 day, then ensiled for 60
      days using a small-scale pouch system. In the pre-ensiled herbages, increasing N
      fertilizer application increased the contents of crude protein and photosynthetic
      pigments, and these contents were also higher at the booting stage compared with
      the heading stage. In the silage, increasing N fertilizer application also
      increased the contents of crude protein, the photosynthetic pigments and their
      derivatives (pheophytin and pheophorbide), while harvesting stage did not affect
      the contents of beta-carotene, chlorophylls or pheophorbide. Nitrogen fertilizer
      application and early harvesting of herbage increased lutein and phytol contents
      in Italian ryegrass silage. Lutein and phytol in Italian ryegrass herbage are
      indicated to be well preserved during ensiling.

PMID- 28436170
TI  - Determination of chlorophenols in water using dispersive liquid-liquid
      microextraction coupled with water-in-oil microemulsion electrokinetic
      chromatography in normal stacking mode.
AB  - The current routes to couple dispersive liquid-liquid microextraction with
      capillary electrophoresis are the evaporation of water immiscible extractants and
      the back-extraction of analytes. In this study, a new methodology for this
      combination using water-in-oil microemulsion electrokinetic chromatography
      coupled with normal stacking mode on-line sample concentration was developed to
      analyze chlorophenols in water samples. The analytes were extracted with tributyl
      phosphate and the extractant dilution (3*) was directly injected into an
      electrophoresis buffer (7.7 cm) containing 5% sodium dodecyl sulfate, 78% 1
      butanol, 2% 1-heptane, and 15% sodium acetate solution (pH 8.0). This proposed
      method is very simple and convenient compared to the conventional procedures. The
      key parameters affecting separation and concentration were systematically
      optimized. Under the optimized conditions, dispersive liquid-liquid
      microextraction contributed an enrichment factor of 45-50, and the overall
      sensitivity improvement was 312-418-fold. Limits of detection between 1.4 and 3.0
      ng/mL and limits of quantification between 4.5 and 10.2 ng/mL were achieved.
      Acceptable repeatability lower than 3.0% for migration time and 9.0% for peak
      areas were obtained. The developed method was successfully applied for analysis
      of the chlorophenols in real water samples.

PMID- 28436169
TI  - Plasma concentrations of lipids during pregnancy and the risk of gestational
      diabetes mellitus: A longitudinal study.
AB  - BACKGROUND: Abnormal lipid profiles have been associated with gestational
      diabetes mellitus (GDM), but studies with longitudinal measures of lipids
      throughout pregnancy are sparse. The aim of the present study was to characterize
      longitudinal changes in lipid profiles throughout pregnancy and prospectively
      examine the associations of plasma lipid concentrations with risk of GDM.
      METHODS: This study was a nested case-control study including 107 GDM cases and
      214 matched non-GDM controls from participants in the National Institute of Child
      Health and Human Development (NICHD) Fetal Growth Studies - Singleton cohort.
      Blood samples were collected longitudinally at Gestational Weeks (GW) 10-14, 15
      26 (fasting sample), 23-31, and 33-39. Plasma concentrations of triglycerides,
      total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured
      by enzymatic assays. Low-density lipoprotein cholesterol (LDL-C) was calculated
      using Friedewald's formula. RESULTS: Plasma triglycerides, total cholesterol, and
      LDL-C increased as pregnancy progressed. At GW 10-14, the adjusted odds ratios
      (aORs) of GDM comparing the highest versus lowest quartile were 3.15 (95%
      confidence interval [CI] 1.38-7.15; P trend  = 0.002) for triglycerides and 0.44
      (95% CI 0.18-1.09; P trend  = 0.045) for HDL-C. At GW 15-26, the aORs were 6.57
      (95% CI 2.25-19.17; P trend  = 0.001) for triglycerides and 0.23 (95% CI 0.08
      0.63; P trend  = 0.005) for HDL-C. No significant associations were observed for
      total cholesterol and LDL-C concentrations with risk of GDM. CONCLUSIONS: Higher
      plasma triglyceride and lower HDL-C concentrations in early and mid-pregnancy
      were significantly associated with a greater risk of GDM. Total cholesterol and
      LDL-C concentrations during pregnancy were not significantly associated with GDM
      risk.

PMID- 28436172
TI  - Indaziflam: a new cellulose-biosynthesis-inhibiting herbicide provides long-term
      control of invasive winter annual grasses.
AB  - BACKGROUND: Indaziflam is a cellulose-biosynthesis-inhibiting (CBI) herbicide
      that is a unique mode of action for resistance management and has broad spectrum
      activity at low application rates. This research further explores indaziflam's
      activity on monocotyledons and dicotyledons and evaluates indaziflam's potential
      for restoring non-crop sites infested with invasive winter annual grasses.
      RESULTS: Treated Arabidopsis, downy brome, feral rye and kochia were all
      susceptible to indaziflam in a dose-dependent manner. We confirmed that
      indaziflam has increased activity on monocots (average GR50  = 231 pm and 0.38 g
      AI ha-1 ) at reduced concentrations compared with dicots (average GR50  = 512 pm
      and 0.87 g AI ha-1 ). Fluorescence microscopy confirmed common CBI symptomologies
      following indaziflam treatments, as well as aberrant root and cell morphology.
      Across five application timings, indaziflam treatments resulted in superior
      invasive winter annual grass control 2 years after treatment (from 84 +/- 5.1% to
      99 +/- 0.5%) compared with imazapic (36% +/- 1.2%). Indaziflam treatments
      significantly increased biomass and species richness of co-occurring species 2
      years after treatment. CONCLUSION: Indaziflam's increased activity on monocots
      could provide a new alternative management strategy for long-term control of
      multiple invasive winter annual grasses that invade >23 million ha of US
      rangeland. Indaziflam could potentially be used to eliminate the soil seed bank
      of these invasive grasses, reduce fine fuel accumulation and ultimately increase
      the competitiveness of perennial co-occuring species. (c) 2017 Society of
      Chemical Industry.

PMID- 28436171
TI  - Sex and regional differences in rabbit right ventricular L-type calcium current
      levels and mathematical modelling of arrhythmia vulnerability.
AB  - NEW FINDINGS: What is the central question of this study? Regional variations of
      ventricular L-type calcium current (ICa-L ) amplitude may underlie the increased
      arrhythmia risk in adult females. Current amplitude variations have been
      described for the left ventricle but not for the right ventricle. What is the
      main finding and its importance? Adult female rabbit right ventricular base
      myocytes exhibit elevated ICa-L compared with female apex or male myocytes.
      Oestrogen upregulated ICa-L in cultured female myocytes. Mathematical simulations
      modelling long QT syndrome type 2 demonstrated that elevated ICa-L prolonged
      action potentials and induced early after-depolarizations. Thus, ventricular
      arrhythmias in adult females may be associated with an oestrogen-induced
      upregulation of ICa-L . Previous studies have shown that adult rabbit left
      ventricular myocytes exhibit sex and regional differences in L-type calcium
      current (ICa-L ) levels that contribute to increased female susceptibility to
      arrhythmogenic early after-depolarizations (EADs). We used patch-clamp recordings
      from isolated adult male and female rabbit right ventricular myocytes to
      determine apex-base differences in ICa-L density and used mathematical modelling
      to examine the contribution of ICa-L to EAD formation. Current density measured
      at 0 mV in female base myocytes was 67% higher than in male base myocytes and 55%
      higher than in female apex myocytes. No differences were observed between male
      and female apex myocytes, between male apex and base myocytes, or in the voltage
      dependences of ICa-L activation or inactivation. The role of oestrogen was
      investigated using cultured adult female right ventricular base myocytes. After 2
      days, 17beta-estradiol (1 nm) produced a 65% increase in ICa-L density compared
      with untreated control myocytes, suggesting an oestrogen-induced upregulation of
      ICa-L . Action potential simulations using a modified Luo-Rudy cardiomyocyte
      model showed that increased ICa-L density, at the level observed in female base
      myocytes, resulted in longer duration action potentials, and when combined with a
      50% reduction of the rapidly inactivating delayed rectifier potassium current
      conductance to model long QT syndrome type 2, the action potential was
      accompanied by one or more EADs. Thus, we found higher levels of ICa-L in adult
      female right ventricle base myocytes and the upregulation of this current by
      oestrogen. Simulations of long QT syndrome type 2 showed that elevated ICa-L
      contributed to genesis of EADs.

PMID- 28436173
TI  - Relationship between endobronchial ultrasound-guided (EBUS)-transbronchial needle
      aspiration utility and computed tomography staging, node size at EBUS, and
      positron emission tomography scan node standard uptake values: A retrospective
      analysis.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) diagnoses and stages mediastinal lymph node pathology. This
      retrospective study determined the relationship between EBUS-TBNA utility and non
      small cell lung cancer (NSCLC) stage, lymph node size, and positron emission
      tomography (PET) standard uptake values (SUV), and the utility of neck ultrasound
      in bulky mediastinal disease. METHODS: Data of 284 consecutive patients who had
      undergone EBUS-TBNA was collected. Two hundred patients had suspected NSCLC, with
      148 confirmed NSCLC cases. The diagnostic utility of EBUS-TBNA was determined
      according to NSCLC stage, EBUS lymph node size, PET SUV, use in distal
      metastases, and mutation testing. The utility of neck ultrasound for N3 disease
      was calculated in patients with bulky mediastinal disease. RESULTS: EBUS-TBNA was
      well tolerated with 97% sensitivity in distant metastatic disease, avoiding the
      need for distal metastases biopsy in 81% of cases. It had equivalent diagnostic
      accuracy in all NSCLC stages and in lymph nodes <10 mm, <20 mm or >20 mm
      (sensitivity >92% in all cases), with no mutation testing failures. EBUS-TBNA had
      33% sensitivity in PET indolent (SUV < 4) nodes and 79% sensitivity in PET active
      nodes (SUV > 4). EBUS-TBNA diagnosed 12 cases of lymphoma without flow cytometry.
      CONCLUSIONS: The use of EBUS-TBNA meant that distant metastatic biopsy was
      avoided in 81% of cases, performing well irrespective of cancer stage, node size,
      and facilitating mutation testing. Neck ultrasound failed to detect N3 disease in
      patients with bulky mediastinal disease. EBUS-TBNA had a sensitivity of 33% for
      metastases in PET negative nodes, highlighting PET limitations.

PMID- 28436174
TI  - Endobronchial and transbronchial biopsy experience: A United Kingdom survey.
AB  - BACKGROUND: Trainees are performing fewer bronchoscopies as a result of the
      increased use of endobronchial ultrasound-guided transbronchial needle
      aspiration. Workforce planning and changes in trainee working patterns may also
      have compounded this situation. We investigated current trends in endobronchial
      biopsy (EBB) and transbronchial biopsy (TBB) training and competency in
      respiratory trainees and consultants across the United Kingdom. METHODS: We
      performed a national survey and received 131 online responses from 58 consultants
      and 73 registrars across 13 United Kingdom deaneries. RESULTS: A significant
      proportion (31%) of consultants, more than half of which were new consultants,
      had performed <500 bronchoscopies. Bronchoscopic biopsy experience varies widely
      across trainees and consultants (9.1% of senior trainees and 14.3% of new
      consultants had performed <100 bronchoscopies). Most trainees and some new
      consultants reported performing relatively low numbers of EBB (13% <20 and 52%
      <50 procedures) and TBB (75% of trainees, 36% of new consultants, 12% of
      established consultants <10 procedures). Significant numbers of trainees do not
      feel competent in EBB (24%) and TBB (89% of junior trainees, 64% of senior
      trainees) and some consultants (24% of new and established consultants) wish for
      support with TBB. CONCLUSIONS: These results have implications for future
      specialist training, curriculum planning, and service configuration. Training and
      performance of EBB and TBB may become concentrated in centers with an adequate
      volume of these procedures. Higher volumes of EBB and TBB may well be more likely
      to occur paradoxically in centers without endobronchial ultrasound-guided
      transbronchial needle aspiration; however, this hypothesis requires further
      study.

PMID- 28436175
TI  - Chronic hypertension and adverse pregnancy outcome: a cohort study.
AB  - OBJECTIVE: To examine the association between chronic hypertension (CH) and a
      wide range of adverse pregnancy outcomes after adjustment for confounding factors
      in obstetric history and maternal characteristics. METHODS: This was a
      prospective screening study for adverse pregnancy outcomes in women with
      singleton pregnancy attending their first routine hospital visit at 11 + 0 to 13
      + 6 weeks' gestation. Data on maternal characteristics, medical and obstetric
      history and pregnancy outcome were collected. Regression analysis was performed
      to examine the association between CH and adverse pregnancy outcomes, including
      late miscarriage, stillbirth, pre-eclampsia (PE), gestational diabetes mellitus
      (GDM), spontaneous and iatrogenic preterm birth (PTB), small-for-gestational-age
      (SGA) neonate, large-for-gestational-age (LGA) neonate and elective and emergency
      Cesarean section (CS). RESULTS: The study population of 109 932 pregnancies
      included 1417 (1.3%) women with CH. After adjusting for potential confounding
      variables from maternal characteristics, medical and obstetric history, CH was
      associated with increased risk of stillbirth (odds ratio (OR), 2.38 (95% CI, 1.51
      3.75)), PE (OR, 5.76 (95% CI, 4.93-6.73)), SGA (OR, 2.06 (95% CI, 1.79-2.39)),
      GDM (OR, 1.61 (95% CI, 1.27-2.05)), iatrogenic PTB < 37 weeks (OR, 3.73 (95% CI,
      3.07-4.53)) and elective CS (OR, 1.79 (95% CI, 1.52-2.11)), decreased risk of LGA
      (OR, 0.65 (95% CI, 0.53-0.78)) and had no significant effect on late miscarriage,
      spontaneous PTB or emergency CS. CONCLUSION: CH should be combined with other
      maternal characteristics and medical and obstetric history when calculating an
      individualized adjusted risk for adverse pregnancy complications. CH increases
      the risk of stillbirth, PE, SGA, GDM, iatrogenic PTB and elective CS and reduces
      the risk for LGA. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28436176
TI  - Does bowel preparation for inflammatory bowel disease surgery matter?
AB  - AIM: The purpose of this study was to determine if bowel preparation influences
      outcomes in patients with inflammatory bowel disease undergoing surgery. METHODS:
      The database of the American College of Surgeons National Surgical Quality
      Improvement Program, Procedure Targeted Colectomy, from 2012 to 2014 was
      analyzed. Inflammatory bowel disease patients undergoing colorectal resection
      with or without bowel preparation were included in the study. RESULTS: In all,
      3679 patients with inflammatory bowel disease were identified. 42.5% had no bowel
      preparation, 21.5% had mechanical bowel preparation only, 8.8% had oral
      antibiotic bowel preparation only and 27.2% had combined mechanical and oral
      antibiotic preparation. Combined mechanical and oral antibiotic preparation is
      associated with lower rates of anastomotic leak, ileus, surgical site infection,
      organ space infection, wound dehiscence and sepsis/septic shock. CONCLUSION:
      Combined mechanical and oral antibiotic preparation for inflammatory bowel
      disease patients undergoing colectomy is associated with decreased rates of
      surgical site infection, anastomotic leak, ileus. Combined bowel preparation
      should be the standard of care for inflammatory bowel disease patients undergoing
      colorectal resection.

PMID- 28436177
TI  - Limited evidence of abnormal intra-colonic pressure profiles in diverticular
      disease - a systematic review.
AB  - AIM: Abnormal colonic pressure profiles and high intraluminal pressures are
      postulated to contribute to the formation of sigmoid colon diverticulosis and the
      pathophysiology of diverticular disease. This study aimed to review evidence for
      abnormal colonic pressure profiles in diverticulosis. METHOD: All published
      studies investigating colonic pressure in patients with diverticulosis were
      searched in three databases (Medline, Embase, Scopus). No language restrictions
      were applied. Any manometry studies in which patients with diverticulosis were
      compared with controls were included. The Newcastle-Ottawa Quality Assessment
      Scale (NOS) for case-control studies was used as a measure of risk of bias. A cut
      off of five or more points on the NOS (fair quality in terms of risk of bias) was
      chosen for inclusion in the meta-analysis. RESULTS: Ten studies (published 1962
      2005) met the inclusion criteria. The studies followed a wide variety of
      protocols and all used low-resolution manometry (sensor spacing range 7.5-15 cm).
      Six studies compared intra-sigmoid pressure, with five of six showing higher
      pressure in diverticulosis vs controls, but only two reached statistical
      significance. A meta-analysis was not performed as only two studies were above
      the cut-off and these did not have comparable outcomes. CONCLUSION: This
      systematic review of manometry data shows that evidence for abnormal pressure in
      the sigmoid colon in patients with diverticulosis is weak. Existing studies
      utilized inconsistent methodology, showed heterogeneous results and are of
      limited quality. Higher quality studies using modern manometric techniques and
      standardized reporting methods are needed to clarify the role of colonic pressure
      in diverticulosis.

PMID- 28436178
TI  - K2 ZnSn3 Se8 : A Non-Centrosymmetric Zinc Selenidostannate(IV) Featuring
      Interesting Covalently Bonded [ZnSn3 Se8 ]2- Layer and Exhibiting Intriguing
      Second Harmonic Generation Activity.
AB  - Non-centrosymmetric zinc selenidostannate(IV) K2 ZnSn3 Se8 was synthesized. It
      features interesting covalently bonded [ZnSn3 Se8 ]2- layers with K+ cations
      filling in the interlayer voids. The phonon spectrum was calculated to clarify
      its structural stability. Based on the X-ray diffraction data along with the
      Raman spectrum, the major bonding features of the title compound were identified.
      According to the UV/vis-NIR spectroscopy, K2 ZnSn3 Se8 possesses a typical direct
      band gap of 2.10 eV, which is in good agreement with the band structure
      calculations. Moreover, our experimental measurements and detailed theoretical
      calculations reveal that K2 ZnSn3 Se8 is a new phase-matchable nonlinear optical
      material with a powder second harmonic generation (SHG) signal about 0.6 times of
      that of AgGaS2 .

PMID- 28436179
TI  - Monogenic diabetes prevalence among Polish children-Summary of 11 years-long
      nationwide genetic screening program.
AB  - BACKGROUND: Estimated monogenic diabetes (MD) prevalence increases as screening
      programs proceeds. OBJECTIVE: To estimate prevalence of MD among Polish children.
      SUBJECTS: Patients and their family members suspected of suffering from MD
      (defined as causative mutation in one of the Maturity Onset Diabetes of the Young
      or permanent neonatal diabetes mellitus genes) were recruited between January
      2005 and December 2015. METHODS: Nationwide prevalence was estimated based on
      data from 6 administrative provinces (out of 16 in Poland) with high referral
      rates of patients (>10 per 100 000 children). RESULTS: During the analysis,
      probands from 322 of 788 screened families tested positive yielding a total of
      409 children and 299 family members with MD. An average of 70 probands/year were
      referred. Screening success rate reached 40% over the study period. We estimated
      the prevalence of MD in 2015 to 7.52/100 000 children (1 in 13 000). The most
      frequent MODY in this group was GCK- MODY (6.88/100 000). The prevalence
      estimates increased nearly 2-fold since our report in 2011 (4.4/100 000).
      However, the figure reached a plateau because of screening saturation in 2014
      what was also proven by lowering of the median age of diagnosis lowered in time
      (R = -0.73, P = .0172) along with shortening of the delay between clinical and
      genetic diagnosis (R = -0.65, P = .0417). CONCLUSIONS: The screening for
      childhood MD in Poland reached a plateau phase after 10 years showing a stable
      prevalence estimate. The true frequency of MD in the overall population may be
      higher given later onset of reportedly more frequent types of MD than GCK -MODY.

PMID- 28436180
TI  - Control mechanisms for producing antimicrobial factors in ruminant mammary gland.
AB  - Mastitis, a symptom of inflammation in mammary tissue by infection with various
      kinds of bacteria, causes huge economic losses in the milk industry. One of the
      popular methods for treatment of mastitis is antibiotics, although this prohibits
      milk shipping and sometimes causes resistant microbes. Therefore, a new strategy
      to treat mastitis without antibiotics is eagerly required around the world.
      Antimicrobial factors belong to innate immunity and can start their function
      extremely early after bacterial stimulation. These factors have antimicrobial
      activity for a broad spectrum of bacteria. Elucidation of causal mechanisms and
      functions of antimicrobial factors in the mammary gland is thought to result in
      suitable methods for prevention and treatment of mastitis. Therefore, this review
      introduces traits of some antimicrobial factors and the mechanisms for
      expressing, producing and secreting them in the mammary gland. For antimicrobial
      factors, lingual antimicrobial peptide (LAP), S100A7, cathelicidin and
      lactoferrin are controlled in different sites and different time courses,
      suggesting that antimicrobial factors play different roles for local defense
      against bacterial infection in the mammary gland. These findings will contribute
      to the development of prevention and treatment methods for mastitis.

PMID- 28436181
TI  - Cortical hyperexcitability and disease spread in amyotrophic lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is characterized by
      focal disease onset with a predominantly contiguous pattern of disease spread.
      The pathophysiological mechanisms underlying disease progression in ALS have not
      been elucidated. Given that cortical hyperexcitability has been identified as an
      important pathogenic mechanism in ALS, the aim of the present study was to
      determine whether changes in cortical function could mediate disease spread in
      ALS. METHODS: Threshold-tracking transcranial magnetic stimulation was undertaken
      in 50 patients with sporadic ALS with recording of responses over both abductor
      pollicis brevis muscles, with results matched to clinical assessments and
      concurrent neurophysiological investigation of lower motor neuron function.
      Subsequently, patients were followed longitudinally to map patterns of clinical
      disease progression. RESULTS: Cortical dysfunction was evident over both motor
      cortices, with hyperexcitability more prominent over the dominant motor cortex,
      contralateral to the site of disease onset, with reduction of resting motor
      threshold (F = 3.83, P < 0.05), short-interval intracortical inhibition (F =
      15.0, P < 0.0001) and cortical silent-period duration (F = 8.01, P < 0.01), along
      with an increase in motor evoked potential amplitude (F = 5.66, P < 0.01). In
      addition, patterns of cortical change were consistent with a contiguous pattern
      of disease progression. CONCLUSIONS: Cortical hyperexcitability appears to be
      more prominent over the dominant motor cortex, contralateral to the side of
      symptom onset, and contributes to a contiguous pattern of spread in sporadic ALS.

PMID- 28436183
TI  - Person-centered dementia care for older veterans with dementia in Taiwan: Past,
      present and future.

PMID- 28436184
TI  - Delaying cognitive and physical decline through multidomain interventions for
      residents with mild-to-moderate dementia in dementia care units in Taiwan: A
      prospective cohort study.
AB  - AIM: To develop experimental multi-domain interventions for older people with
      mild-to-moderate dementia, and to evaluate the effect of delaying cognitive and
      physical decline, and improvement or prevention of geriatric syndromes during 1
      year follow up. METHODS: Participants aged 65 years and older with mild-to
      moderate dementia (clinical dementia rating [CDR] 1 or 2) were grouped as
      intervention in Jia-Li Veterans Home and usual care model in the community
      (Memory clinic). All residents in Jia-Li Veterans Home received comprehensive
      intervention, including Multi-disciplinary team consultation and intervention,
      Multi-component non-pharmacological management, geriatric syndromes survey and
      intervention by CGA, and a dementia friendly medical Green channel Approach
      (2MCGA). The decline of cognitive and physical function are determined by the
      change of Mini-Mental State Examination score, CDR and the sum of CDR box, as
      well as activities of daily living based on the Barthel Index. We also screened
      geriatric syndromes at baseline and 1 year later. RESULTS: Participants in the
      intervention group were older and had a lower educational level, lower body mass
      index, poor baseline activities of daily living function, lower visual
      impairment, and higher rates of hearing impairment, polypharmacy and risk of
      malnutrition. The residents receiving 2MCGA had lower baseline Mini-Mental State
      Examination scores, and higher CDR. For residents in Jia-Li Veterans Home, all
      cognitive measurements except Mini-Mental State Examination were significantly
      associated with delaying the decline of cognition after analyzing by multiple
      linear regression, and multivariate logistic regression also showed that patients
      living in the community was independently associated with a higher odds ratio for
      activities of daily living decline (3.180, 95% CI 1.384-7.308, P = 0.006). There
      are also more improvement in their baseline geriatric syndromes and suffered less
      from new geriatric syndromes, including falls, urinary incontinence, and risk of
      malnutrition. CONCLUSIONS: The 2MCGA intervention shows strong delays in the
      decline of cognition and physical function for older residents with mild-to
      moderate dementia. Furthermore, this strategy can also improve or prevent the
      onset of new geriatric syndromes, especially fall episodes, urinary incontinence
      and risk of malnutrition. Geriatr Gerontol Int 2017; 17 (Suppl. 1): 36-43.

PMID- 28436185
TI  - Predictive factors for dementia and cognitive impairment among residents living
      in the veterans' retirement communities in Taiwan: Implications for cognitive
      health promotion activities.
AB  - AIM: To identify potentially modifiable risk factors for cognitive decline among
      veterans' home residents in Taiwan METHODS: The present retrospective cohort
      study was part of the Veteran Affairs-Comprehensive Geriatric Assessment study
      that retrieved data of the comprehensive geriatric assessment for 946 residents
      living at four veterans' homes in Taiwan. The study participants were interviewed
      every 3-6 months from January 2012 and December 2014. Demographic
      characteristics,multimorbidity by Charlson's Comorbidities Index, physical
      function by the Barthel Index, cognition by the Mini-Mental State Examination
      (MMSE), depression by the five-item Geriatric Depression Scale and nutritional
      status by the Mini-Nutrition Assessment-Short Form were collected for analysis. A
      generalized estimating equation model was used after it was adjusted for age,
      educational level, five-item Geriatric Depression Scale, and problem of
      communication difficulty to identify potential modifiable risk factors for
      cognitive decline. RESULTS: The mean age of the participants was 85.7 +/- 5.2
      years, with a mean follow-up period of 41 +/- 21.6 weeks. The prevalence of
      cognitive impairment (defined by MMSE <24) was 65.6%, whereas 34% of the study
      participants were positive for depressive symptoms. Approximately one-fifth of
      the study participants were using psychotropic agents, which was higher among
      participants with cognitive impairment (23.6% vs 15.6%, P < 0.05) than those
      without. In the generalized estimating equation model, physical function,
      nutritional status, depressive symptoms, ex-drinker, multimorbidity and stool
      incontinence were positively correlated with MMSE score; whereas advanced age,
      low educational level (<6 years), presence of communication difficulty and use of
      psychotropic agents were inversely associated with the MMSE score. CONCLUSIONS:
      Physical function and nutritional status were positively associated with the MMSE
      score, and use of psychotropic agents was negatively correlated with cognitive
      function. Further intervention study is required to improve the cognitive health
      of older adults living in the veterans' retirement communities. Geriatr Gerontol
      Int 2017: 17 (Suppl. 1): 7-13.

PMID- 28436186
TI  - Protective factors against cognitive decline among community-dwelling middle-aged
      and older people in Taiwan: A 6-year national population-based study.
AB  - AIM: Dementia and cognitive impairment are important public health challenges to
      a rapidly aging country. The present study aimed to explore the protective
      factors against cognitive decline among community-dwelling middle-aged and older
      people from health, social, and lifestyle perspectives. METHODS: Data of the
      Social Environment and Biomarkers of Aging Study, a population-based cohort study
      in Taiwan, were retrieved for the study. Overall, 676 participants with intact
      baseline cognitive function (measured by the Short Portable Mental Status
      Questionnaire) were enrolled and followed for six years. Any increasing score of
      the Short Portable Mental Status Questionnaire in the observational period was
      referred to as cognitive function decline. Associated factors for cognitive
      decline were identified by the logistic regression model. RESULTS: Among all
      participants, 205 (30%) experienced cognitive decline during the study period.
      Crude logistic regression showed that women (odds ratio [OR] 1.9, 95% confidence
      interval [CI] 1.3-2.6), low educational level (OR 2.0, 95% CI 1.4-3.0) and low
      mastery (OR 1.4, 95% CI 1.0-1.9) were associated with cognitive decline, but no
      daily consumption of vegetables and fruits had only a marginal association (OR
      1.3, 95% CI 0.9-1.8). In the fully adjusted logistic regression analysis, old
      age, women, low educational level and low sense of mastery were independent
      predictors for cognitive decline. Participants with two modifiable factors
      (mastery, and daily consumptions of vegetables and fruits) had a lower risk of
      cognitive decline (OR 0.5, 95% CI 0.3-0.9), compared with those without any
      protective factor. CONCLUSIONS: Participants with a better educational level,
      better personal mastery, and more consumption of fruits and vegetables were less
      likely to experience cognitive decline. An intervention study combining these
      features should be carried out to promote better cognitive health in communities.
      Geriatr Gerontol Int 2017: 17 (Suppl. 1): 20-27.

PMID- 28436187
TI  - Slow gait speed as a predictor of 1-year cognitive decline in a veterans'
      retirement community in southern Taiwan.
AB  - AIM: Slow gait speed has been associated with mortality, poor physical function
      and disability in older people. Our aim was to evaluate the association between
      slow gait speed and rapid cognitive decline among oldest-old men in Taiwan.
      METHODS: We carried out a longitudinal cohort study in a veterans' retirement
      community, and enrolled 249 male residents aged 80 years and older. Slow gait
      speed was defined as <1 m/s, and rapid cognitive decline was defined as a Mini
      Mental State Examination (MMSE) decline of >=3 points over 1 year. Body mass
      index, Charlson's Comorbidity Index, handgrip strength, gait speed and Mini
      Mental State Examination datasets were collected, and a logistic regression model
      was built to evaluate the association between fast cognitive decline and slow
      gait speed. RESULTS: In all, 249 residents (mean age 86.4 +/- 4.01 years) were
      recruited, including 58 (23.3%) with rapid cognitive decline. Univariate analysis
      showed that slow gait speed could predict rapid cognitive decline (OR 4.10, 95%
      CI 1.20-14.00, P = 0.024). After adjusting for age, Charlson's Comorbidity Index,
      polypharmacy, psychiatric drug usage, cigarette smoking experience, baseline
      cognitive function, depressive mood, handgrip strength, nutritional status and
      history of fall, slow gait speed was still independently associated with rapid
      cognitive decline (adjusted OR 4.58, 95% CI 1.22-17.2, P = 0.024). CONCLUSIONS:
      Slow gait speed was thus an independent predictor of rapid cognitive decline in
      oldest-old men in a veterans' retirement community in Taiwan. Geriatr Gerontol
      Int 2017: 17 (Suppl. 1): 14-19.

PMID- 28436189
TI  - Medication appropriateness for patients with dementia approaching the end of
      their life.
AB  - AIM: To examine medication use among patients with dementia towards the end of
      their life and to evaluate the appropriateness of medication use by using a
      nationwide database. METHODS: Using Taiwan's National Health Insurance Research
      Database, we identified 6532 people with dementia that died between 2008 and
      2012. For each person with dementia, data of medication use in the last month of
      outpatient setting (vs -12th month [baseline]) and last hospitalization (vs -3rd
      hospitalization [baseline]) before death were retrieved for study. The
      medications of interest were selected according to a consensus recommendation,
      which included five categories defining their appropriateness (i.e. always,
      sometimes, rarely and never appropriate, as well as no consensus). Multivariable
      logistic regression was carried out to analyze the determinants for use of "never
      appropriate" medications. RESULTS: Approximately 10% of the study participants
      were prescribed medications categorized as "never appropriate" in the last month
      of life in the outpatient settings, which was significantly lower than their
      baseline (-12th month: 17.5%; P < 0.0001). A similar pattern was identified in
      the last hospitalization before death. Older age was associated with a lower
      likelihood of being prescribed "never appropriate" medications (age 75-84: aOR
      0.34 [0.29-0.41], P < 0.0001; age >=85: aOR 0.34 [0.28-0.40], P < 0.0001). In
      contrast, patients with a history of diabetes mellitus (aOR 1.31 [1.10-1.55], P =
      0.0018) were associated with a higher likelihood of being prescribed "never
      appropriate" medications. CONCLUSIONS: This is the first study to sophisticatedly
      describe medications use, particularly according to their appropriateness for
      palliative care, in Asian people with dementia at the end of their life.
      Approximately 10% of all patients were prescribed "never appropriate" medications
      at the end of their life, which deserves further study to evaluate the clinical
      impact of the quality of care. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 65-74..

PMID- 28436190
TI  - Is gait speed a risk factor for dementia?

PMID- 28436191
TI  - Hospitalization and associated factors in people with Alzheimer's disease
      residing in a long-term care facility in southern Taiwan.
AB  - AIM: It has been reported that many people with dementia require
      hospitalizations. The objective of the present study was to determine predictive
      factors for hospitalizations in people with dementia. METHODS: A total of 70
      individuals with dementia living in a veterans' home in southern Taiwan were
      consecutively enrolled. During prospective follow up, all hospitalization events
      were recorded. RESULTS: The mean age of residents with dementia was 86.1 +/- 4.0
      years, and the mean follow-up time for this population was 2.2 +/- 1.1 years.
      Among individuals, 62.9% suffered from malnutrition or were at risk of
      malnutrition (minimal nutritional assessment-short form score <=11), and 8.6% of
      individuals had a body mass index of <18.5 Kg/m2 . There were 52 (74.3%)
      individuals who had previously fallen. Overall, 51 of 70 residents were
      hospitalized during the follow-up period. In those individuals with previous
      falls, there was a significantly increased risk of hospitalization (odds ratio
      5.61, 95% CI 1.18-26.7). Furthermore, three factors were significantly associated
      with the risk of fall, including handgrip strength, malnutrition and Mini-Mental
      State Examination score. CONCLUSIONS: The results of the present study showed
      that hospitalization was a frequent event in residents with dementia living in a
      long-term care facility. The major predictor for hospital admission was history
      of a previous fall. Screening those with dementia for history of injurious falls
      and associated risk factors for falling could help identify those at risk of
      hospitalization, thus necessitating a comprehensive intervention to reduce
      hospitalization. Geriatr Gerontol Int 2017; 17 (Suppl. 1): 50-56.

PMID- 28436192
TI  - Predictors of non-pharmacological intervention effect on cognitive function and
      behavioral and psychological symptoms of older people with dementia.
AB  - AIM: Our previous work showed that non-pharmacological interventions could
      effectively reduce the severity of behavioral and psychological symptoms of
      dementia (BPSD), while the factors influencing the effect of intervention were
      less explored. Therefore, the main purpose of the present study was to
      investigate the predictors of the non-pharmacological intervention effect for old
      veterans with dementia and BPSD. METHODS: A total of 141 old veterans with
      dementia living in two veterans' homes in northern Taiwan were recruited. The
      participants received an organized non-pharmacological intervention program of
      physical activity/exercise, music therapy, reality orientation, art therapy,
      reminiscence therapy and horticultural therapy once every week for 6 months. All
      participants were evaluated by the Barthel Index, Lawton-Brody Instrumental
      Activities of Daily Living Scale, Mini-Mental State Examination, neuropsychiatric
      inventory (NPI), and the Cornell Scale for Depression in Dementia before and
      after the intervention. Logistic regression was used to investigate factors
      associated with improvement/maintenance of cognition (measured by the Mini-Mental
      State Examination), and improvement of BPSD (measured by NPI) and its subdomains
      during the intervention period. RESULTS: Multivariate logistic regression
      analysis showed that the improvement/maintenance of cognitive function was
      independently associated with a lower Mini-Mental State Examination score at
      baseline (odds ratio [OR] 0.88, 95% CI 0.80-0.97, P = 0.008), whereas
      participants with antipsychotic use were less likely to gain the effect (OR 0.42,
      95% CI 0.17-1.04, P = 0.061). In addition, the improvement of BPSD was associated
      with a higher baseline total NPI score (OR 1.33, 95% CI 1.15-1.55, P < 0.001),
      and the result was consistent in different NPI subdomains (psychotic domain: OR
      1.96, 95% CI 0.83-4.58, P = 0.123; affective domain: OR 1.63, 95% CI 1.25-2.13, P
      < 0.001; behavior domain: OR 2.25, 95% CI 1.53-3.30, P < 0.001) and caregiver
      burden (OR 1.63, 95% CI 1.24-2.14, P < 0.001). In addition, a higher Cornell
      Scale for Depression in Dementia score was correlated with an improvement in the
      NPI behavior domain (OR 1.48, 95% CI 1.01-2.18, P = 0.047), whereas participants
      with hearing impairment had a lower chance of improvement in the NPI behavior
      domain (OR 0.11, 95% CI 0.01-1.23, P = 0.073) and care burden (OR 0.17, 95% CI
      0.03-0.99, P = 0.050). CONCLUSIONS: Our findings show that non-pharmacological
      intervention programs have a significant effect on reducing overall NPI score,
      NPI caregiver burden score and NPI subdomains - psychotic, affective and behavior
      syndrome - in old veterans with dementia. In addition, participants with lower
      cognitive performance, more severe BPSD and depressive symptoms at baseline were
      more likely to gain benefit from the intervention, whereas antipsychotic use and
      hearing impairment were negative predictors of improvement of cognition and BPSD,
      respectively. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 28-35.

PMID- 28436193
TI  - Association between using medications with anticholinergic properties and short
      term cognitive decline among older men: A retrospective cohort study in Taiwan.
AB  - AIM: The use of anticholinergic drugs had been strongly linked to adverse health
      outcomes among older adults, especially in cognitive impairment or dementia. The
      present study aimed to evaluate the cognitive decline related to the use of
      anticholinergic drugs among older men living in the veterans' homes in Taiwan.
      METHODS: This retrospective cohort study was a substudy of The Longitudinal Older
      Veterans study. A total of 274 residents living in four Taiwan veterans' homes
      and receiving two consecutive Mini-Mental State Examinations within the interval
      of 6 months from January 2012 to December 2014 were enrolled in the present
      study. The medication lists for all participants were reviewed by the same
      physician, and the anticholinergic properties of the individual medications were
      evaluated by using the Anticholinergic Cognitive Burden scale. Cognitive decline
      was defined as the decrease of Mini-Mental State Examinations scores during the
      study period. RESULTS: Overall, 139 persons (50.7%) had exposure to
      anticholinergic drugs at baseline (designated as AC[+]), and the most frequently
      used anticholinergic drugs were cardiovascular drugs (48.2%), antipsychotics
      (21.6%), theophylline (20.1%), antidepressants (12.2%), gastrointestinal drugs
      (11.5%) and antihistamines (8.6%). After adjusting for covariates, AC(+)
      participants had a significantly higher risk for short-term cognitive decline (OR
      2.69, 95% CI 1.36-5.31). After excluding 30 participants using antipsychotics,
      non-antipsychotics AC(+)participants still had a significantly higher risk for
      short-term cognitive decline (OR 2.24, 95% CI 1.26-3.99). CONCLUSIONS: Exposure
      to anticholinergic drugs significantly increased the risk for short-term
      cognitive decline among older men, and the adverse effects remained similar when
      antipsychotics were excluded for analysis. A further intervention study is
      required to evaluate whether reducing anticholinergic burden might improve
      cognitive function among older adults. Geriatr Gerontol Int 2017: 17 (Suppl. 1):
      57-64.

PMID- 28436194
TI  - Impact of living arrangements on clinical outcomes among older patients with
      dementia or cognitive impairment admitted to the geriatric evaluation and
      management unit in Taiwan.
AB  - AIM: To evaluate the impact of living arrangements on mortality and functional
      decline among older patients with dementia or cognitive impairment after
      discharge from a geriatric evaluation and management unit (GEMU) in Taiwan.
      METHODS: The present retrospective cohort study used data from the Veteran
      Affairs Comprehensive Geriatric Assessment from January 2015 to May 2016 for
      analysis. Data of patients aged 65 years and older with dementia or cognitive
      impairment at admission to the GEMU of Taipei Veterans General Hospital during
      the study period were retried for study. The Veteran Affairs Comprehensive
      Geriatric Assessment included demographic characteristics, Clinical Frailty
      Scale, Braden Scale, St. Thomas's Risk Assessment Tool in Falling Elderly
      Inpatients Scale, Cumulative Illness Rating Scale for Geriatrics, Barthel Index,
      Instrumental Activities of Daily Living, Mini-Mental State Examination, Geriatric
      Depression Scale-5 and Mini-Nutritional Assessment - Short Form, as well as
      common geriatric syndromes. All patients were categorized into the home care
      group and institutional care group based on their living arrangement before GEMU
      admissions. Six-month mortality and decline in Barthel Index were defined as
      adverse clinical outcomes. RESULTS: Overall, data of 395 patients were used for
      analysis. The baseline comparisons showed that the institutional care group was
      more likely to be unmarried, have lower education, lower risk of falls and less
      polypharmacy, but more likely to experience functional decline at follow up than
      the home care group. Multivariate logistic regression showed that male (OR 3.59,
      95% CI 1.04-12.38, P = 0.043) and higher Cumulative Illness Rating Scale for
      Geriatrics score (OR 4.08, 95% CI 1.49-11.19, P = 0.006) were associated with
      mortality, whereas the institutional care group (OR 0.30, 95% 0.09-0.99, P =
      0.048) and lower Braden Scale (OR 0.80, 95% CI 0.67-0.94, P = 0.008) were
      protective against mortality. However, the institutional care group was
      independently associated with functional decline during the follow-up period (OR
      2.19, 95% CI 1.12-4.29, P = 0.022). CONCLUSIONS: Institutional care was
      associated with lower 6-month mortality risk for patients with dementia or
      cognitive impairment after discharge from the GEMU, but this group was more
      likely to experience functional decline. Further prospective study is required to
      clarify the clinical impact of living arrangements on long-term outcomes when
      people with dementia or cognitive impairment are admitted to acute hospitals.
      Geriatr Gerontol Int 2017: 17 (Suppl. 1): 44-49.

PMID- 28436195
TI  - Organocatalytic Enantioselective Acyloin Rearrangement of alpha-Hydroxy Acetals
      to alpha-Alkoxy Ketones.
AB  - We report an unprecedented organocatalytic enantioselective acyloin rearrangement
      of alpha,alpha-disubstituted alpha-hydroxy acetals. In the presence of a
      catalytic amount of chiral binol-derived N-triflyl phosphoramide, alpha-hydroxy
      acetals rearranged to alpha-alkoxy ketones in good to high yields with high
      enantioselectivities. Formation of an ion pair between the in situ generated
      oxocarbenium ion and the chiral phosphoramide anion was proposed to be
      responsible for the highly efficient transfer of chirality. Conditions for
      removal of cyclohexyl and cyclopentyl groups from the corresponding alpha-alkoxy
      ketones were uncovered underpinning their potential general utility as hydroxy
      protecting groups. Conversion of the rearranged products to the enantioenriched
      alpha-hydroxy ketone, 1,2-diol, beta-amino alcohol and 1,4-dioxane was also
      documented.

PMID- 28436196
TI  - Bone mineral density and fractures after surgical menopause: systematic review
      and meta-analysis.
AB  - BACKGROUND: Oophorectomy is recommended for women at increased risk for ovarian
      cancer. When performed at premenopausal age oophorectomy induces acute surgical
      menopause, with unwanted consequences. OBJECTIVE: To investigate bone mineral
      density (BMD) and fracture prevalence after surgical menopause. SEARCH STRATEGY:
      A literature search of PubMed, EMBASE and Cochrane library was performed with no
      date restriction. Date of last search was March 1st, 2016. SELECTION CRITERIA:
      Primary studies reporting on BMD, T-scores or fracture prevalence in women with
      surgical menopause and age-matched control groups. DATA COLLECTION AND ANALYSIS:
      Data were extracted on BMD (g/cm2 ), T-scores and fracture prevalence in women
      with surgical menopause and control groups. Quality was assessed by an adaptation
      of the Downs and Black checklist. Random effects models were used to meta-analyse
      results of studies reporting on BMD or fracture rates. MAIN RESULTS: Seventeen
      studies were included, comprising 43 386 women with surgical menopause. Ten
      studies provided sufficient data for meta-analysis. BMD after surgical menopause
      was significantly lower than in premenopausal age-matched women [mean difference
      lumbar spine, -0.15 g/cm2 (95% CI, -0.19 to -0.11 g/cm2 ); femoral neck, -0.17
      g/cm2 (95% CI, -0.23 to -0.11 g/cm2 )] but not lower than in women with natural
      menopause [lumbar spine, -0.02 g/cm2 (95% CI, -0.04 to 0.00 g/cm2 ); femoral
      neck, 0.04 g/cm2 (95% CI, -0.09 to 0.16 g/cm2 )]. Hip fracture rate was not
      higher after surgical menopause compared with natural menopause [hazard ratio:
      0.85 (95% CI, 0.70 to 1.04)]. AUTHOR'S CONCLUSIONS: No evident effect of surgical
      menopause was observed on BMD and fracture prevalence compared with natural
      menopause. However, available studies are prone to bias and need to be
      interpreted with caution. TWEETABLE ABSTRACT: Bone health after menopause: no
      evidence for additional effect of surgical menopause on BMD and fractures.

PMID- 28436197
TI  - Magnetic resonance imaging following neoadjuvant chemoradiation and transanal
      endoscopic microsurgery for rectal cancer.
AB  - AIM: Full-thickness local excision after neoadjuvant chemoradiotherapy (CRT) for
      patients with rectal cancer and incomplete clinical response has been a treatment
      strategy for organ preservation. Follow-up of these patients is challenging since
      anatomic distortion and postoperative changes may be clinically indistinguishable
      from tumour recurrence. MRI may have a role in detecting recurrence. The aim of
      this study was to describe the MRI findings during follow-up in patients having
      local excision following CRT with and without local recurrence. METHOD: The data
      were collected retrospectively from a single centre. Fifty-three patients with
      rectal cancer who had full-thickness local excision after neoadjuvant CRT and
      near-complete response were eligible for the study. Patients with local
      recurrence were treated by radical salvage surgery. The main outcome was local
      MRI assessment findings during follow-up. RESULTS: Fifteen patients (five who
      developed local recurrence and 10 with no evidence of local recurrence) had MR
      images available for review and were included in the study. High signal intensity
      and thickening of the rectal wall were present in all patients with recurrent
      disease within the rectal wall. Overall, 80% of the patients with recurrence
      showed diffusion restriction. MRI mesorectal fascia status and circumferential
      resection margin showed agreement in all cases. A low signal intensity scar was
      seen in all patients without recurrent disease. CONCLUSION: MRI shows high signal
      intensity and thickening of the rectal wall in recurrent disease in comparison to
      a low signal intensity fibrotic scar in non-recurrent disease. These findings may
      be useful in surveillance of these patients.

PMID- 28436199
TI  - A Method for the Late-Stage Formation of Ketones, Acyloins, and Aldols from
      Alkenylstannanes: Application to the Total Synthesis of Paecilonic Acid A.
AB  - Treatment of alkenylstannanes with Cu(OAc)2 /Et3 N affords the corresponding enol
      esters or ketones under conditions that proved compatible with many common
      functionalities; these include groups that would neither survive under the
      standard Tamao-Fleming conditions for the oxidation of Csp2 -SiR3 bonds nor under
      the conditions commonly used to oxidize C-B bonds. Chiral centers adjacent to the
      unveiled carbonyls are not racemized and competing protodestannation is marginal,
      even if the substrate carries unprotected -OH groups as internal proton sources.
      Therefore, the procedure is well suited for the preparation of acyloin and aldol
      derivatives. These enabling virtues are illustrated by a concise approach to the
      bicyclic lipid paecilonic acid A.

PMID- 28436198
TI  - Effects of selenium on apoptosis and abnormal amino acid metabolism induced by
      excess fatty acid in isolated rat hepatocytes.
AB  - SCOPE: Increased serum free fatty acid (FFA) occurs in subjects with non
      alcoholic fatty liver disease (NAFLD) and also triggers oxidative stress,
      apoptosis, and insulin resistance. Selenium (Se) is an antioxidant agent.
      However, the effect of Se on NAFLD or diabetes is still unclear. We investigated
      the effect of Se on apoptosis and abnormal amino acid metabolism initiated by
      excess FFA in isolated rat hepatocytes. METHODS AND RESULTS: Primary hepatocytes
      from rats were isolated and exposed to excessive FFA (0.5 mM oleate/palmitic acid
      2:1) and 0.1 MUM Se. Se protected primary hepatocytes against oxidative stress
      and apoptosis induced by excess FFA, but did not play a role on abnormal amino
      acid metabolism and insulin resistance initiated by FFA in isolated rat
      hepatocytes. CONCLUSION: Although Se had the capability of preventing the
      apoptosis initiated by ROS, insulin resistance failed to be reversed in
      hepatocytes exposed to FFA. This failure may be attributed to the limitation of
      Se in regulating branched chain amino acids abundance. This indicates that
      apoptosis and insulin resistance might be involved in different pathways when
      isolated hepatocytes were exposed to FFA and Se.

PMID- 28436200
TI  - Randomised controlled trial shows that co-bedding twins may reduce birthweight
      recovery delay, parenteral nutrition weaning time and hospitalisation.

PMID- 28436201
TI  - Brain responses to mechanical rectal stimulation in patients with faecal
      incontinence: an fMRI study.
AB  - AIM: Continence is dependent on anorectal-brain interactions. Consequently,
      aberrations of the brain-gut axis may be important in the pathophysiology of
      faecal incontinence (FI) in certain patients. The aim of this study was to assess
      the feasibility of recording brain responses to rectal mechanical stimulation in
      patients with FI using functional magnetic resonance imaging (fMRI). METHOD: A
      prospective, cohort pilot study was performed to assess brain responses during
      rectal stimulation in 14 patients [four men, mean (SD) age 62 (15) years]. Blood
      oxygen level dependent (BOLD) signals were measured by fMRI during rest and
      mechanical distension, involving random repetitions of isobaric phasic rectal
      distensions at fixed (15 and 45 mmHg) and variable (10% above sensory perception
      threshold) pressures. RESULTS: Increases in BOLD signals in response to high
      pressure rectal distension (45 mmHg) and maximum toleration were observed in the
      cingulate gyrus, thalamus, insular cortex, inferior frontal gyrus, cerebellum,
      caudate nucleus, supramarginal gyrus, putamen and amygdala. Additionally,
      activation of the supplementary motor cortex and caudate nucleus with
      inconsistent activity in the frontal lobe was observed. CONCLUSIONS: This study
      has demonstrated the feasibility of recording brain responses to rectal
      mechanical stimulation using fMRI in patients with FI, revealing activity in
      widespread areas of the brain involved in visceral sensory processing. The
      observed activity in the supplementary motor cortex and caudate nucleus, with
      relative paucity of activity in the frontal lobes, warrants investigation in
      future studies to determine whether aberrations in cerebral processing of rectal
      stimuli play a role in the pathogenesis of FI.

PMID- 28436202
TI  - A common genetic variant in FOXP2 is associated with language-based learning
      (dis)abilities: Evidence from two Italian independent samples.
AB  - Language-based Learning Disabilities (LLDs) encompass a group of complex,
      comorbid, and developmentally associated deficits in communication. Language
      impairment and developmental dyslexia (DD) represent the most recognized forms of
      LLDs. Substantial genetic correlations exist between language and reading
      (dis)abilities. Common variants in the FOXP2 gene were consistently associated
      with language- and reading-related neuropsychological and neuroanatomical
      phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093
      (A/G), on quantitative measures of language and reading in two independent
      Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a
      sample of 572 children with DD (6-18 years old). rs6980093 modulates expressive
      language in the general population sample, with an effect on fluency scores. In
      the DD sample, the variant showed an association with the accuracy in the single
      word reading task. rs6980093 shows distinct genetic models of association in the
      two cohorts, with a dominant effect of the G allele in the general population
      sample and heterozygote advantage in the DD cohort. We provide preliminary
      evidence that rs6980093 associates with language and reading (dis)abilities in
      two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it
      (or a linked variant) modulates phenotypic association via regulation of FOXP2
      expression. Because FOXP2 brain expression is finely regulated, both temporally
      and spatially, it is possible that the two alleles at rs6980093 differentially
      modulate expression levels in a developmental stage- or brain area-specific
      manner. This might help explaining the heterozygote advantage effect and the
      different genetic models in the two cohorts.

PMID- 28436204
TI  - Disabled graduate-entry medical student experience.
AB  - BACKGROUND: This study explored the experiences of graduate-entry medicine degree
      programme students who were disabled on the disclosure of their disability and
      the challenging disability issues they encountered during their degree programme.
      METHODS: Eight student volunteers with a disability from the University of
      Warwick graduate-entry medicine degree programme took part in this study. Audio
      recordings of their semi-structured interviews were transcribed verbatim and
      analysed thematically. FINDINGS: Contributory factors to a reluctance or delay in
      disclosing disability to the medical school included confidentiality concerns,
      the potential impact of disclosure on their medical school application outcome
      and not perceiving their disability had an impact on their ability to function.
      They disclosed their disability for a range of professional and practical
      considerations. One participant was investigated and diagnosed with dyslexia
      following failure in a medical school examination. Disabled medical students
      encountered challenging issues such as having concerns about their future fitness
      to practice and employability, repeated disclosure of disability,
      confidentiality, abuse and difficulties in organising reasonable adjustments.
      Disabled medical students encounter challenging issues DISCUSSION: Medical school
      staff should keep an open mind about undiagnosed disability as a potential
      contributory factor to graduate students' academic underperformance. Participants
      expressed concerns about the management of their disability information that
      could potentially be addressed through regular dialogue between the students with
      a disability and medical school representatives, to define who, when and how
      other staff members could have access to the students' disability information.
      Despite the challenges students with a disability encountered during their degree
      programme, they viewed themselves as individuals who were in a good position to
      empathise with patients and understand their needs.

PMID- 28436205
TI  - Detection of a new HLA-B*44 allele, HLA-B*44:02:45, by monoallelic Sanger
      sequencing.
AB  - Sequence of the novel allele, HLA-B*44:02:45, differs from HLA-B*44:02:01:01 by 1
      nucleotide exchange in exon 2.

PMID- 28436203
TI  - Endoplasmic reticulum proteostasis impairment in aging.
AB  - Perturbed neuronal proteostasis is a salient feature shared by both aging and
      protein misfolding disorders. The proteostasis network controls the health of the
      proteome by integrating pathways involved in protein synthesis, folding,
      trafficking, secretion, and their degradation. A reduction in the buffering
      capacity of the proteostasis network during aging may increase the risk to
      undergo neurodegeneration by enhancing the accumulation of misfolded proteins. As
      almost one-third of the proteome is synthetized at the endoplasmic reticulum
      (ER), maintenance of its proper function is fundamental to sustain neuronal
      function. In fact, ER stress is a common feature of most neurodegenerative
      diseases. The unfolded protein response (UPR) operates as central player to
      maintain ER homeostasis or the induction of cell death of chronically damaged
      cells. Here, we discuss recent evidence placing ER stress as a driver of brain
      aging, and the emerging impact of neuronal UPR in controlling global proteostasis
      at the whole organismal level. Finally, we discuss possible therapeutic
      interventions to improve proteostasis and prevent pathological brain aging.

PMID- 28436206
TI  - Clinical practice guidelines on iron therapy: A critical evaluation.
AB  - Anemia is common among patients with chronic kidney disease (CKD) and it is
      managed primarily with erythropoiesis-stimulating agents (ESA) and iron therapy.
      Following concerns around ESA therapy and economic constraints, IV iron is more
      and more administered worldwide. Several guidelines or position papers, which
      give indications on iron therapy in CKD patients, have been issued in Nephrology.
      Unfortunately, the field is characterized by a lack of evidence. As a result, the
      recommendations/suggestions are not uniform. There is general consensus to
      prescribe iron therapy to patients who are clearly iron deficient. In addition,
      iron therapy may increase Hb values, delay the start of ESA therapy in ESA-naive
      patients and reduce ESA dose in ESA-treated patients. However, there is debate on
      the safety and efficacy of IV iron therapy when given in the presence of already
      high serum ferritin levels. In addition, not all the guidelines/position papers
      differentiate between non-dialysis/dialysis patients and between the
      presence/absence of ESA therapy. Many international Bodies or Societies suggest
      caution when administering IV iron during infections. A trial of oral iron should
      be considered as a first step, especially in the ND-CKD population. Finally,
      recommendations on the prevention of anaphylactic reactions following IV iron
      therapy are given by several bodies. There is consensus that IV iron is to be
      administered in the presence of resuscitative facilities (including medications)
      and personnel trained for emergencies.

PMID- 28436207
TI  - Racial differences in the association between heart rate variability and left
      ventricular mass.
AB  - NEW FINDINGS: What is the central question of this study? Decreased heart rate
      variability (HRV) is associated with increased cardiovascular disease (CVD) risk,
      including greater left ventricular mass (LVM). Despite their enhanced CVD risk
      profile, African Americans have been shown to exhibit higher HRV, relative to
      Whites; however, it is unclear whether this pattern extends to the association
      between HRV and LVM. What is the main finding and its importance? Using ECG and
      echocardiographic data, HRV was positively associated with LVM in a non-clinical
      sample of African Americans. These findings suggest that current assumptions
      regarding the meaning of higher HRV might not be universal, which might have
      implications for HRV as a risk marker among African Americans. Increased left
      ventricular mass (LVM) is an early precursor of target organ damage attributable
      to hypertension. Diminished parasympathetic cardiac control has been linked to
      both hypertension onset and left ventricular impairment; however, emerging
      evidence suggests that this pattern might be different in African Americans. The
      present study sought to determine whether race impacts the relationship between
      parasympathetic cardiac control and LVM. The LVM was assessed via
      echocardiography in a sample (n = 148) of African American and White adults (mean
      age 33.20 +/- 5.71 years) with normal or mildly elevated blood pressure.
      Parasympathetic cardiac control was assessed by a measure of high-frequency heart
      rate variability (HF-HRV) determined from ECG recordings during 5 min of rest. In
      regression analysis, greater HF-HRV was associated with greater LVM among African
      Americans (P = 0.002) but was not related to LVM in Whites (P = 0.919). These are
      the first data to demonstrate that race moderates the relationship between HRV
      and LVM and further suggest that race might be an important factor in the
      association between parasympathetic cardiac control and other cardiovascular
      disease risk factors.

PMID- 28436209
TI  - Medication prior authorization in pediatric hematology and oncology.
AB  - BACKGROUND: Medication prior authorization (PA) is a commonly occurring
      requirement, particularly for medications used for rare conditions. Based on
      standard definitions, cancer and many blood disorders affecting children are
      rare. The study aims were to describe the relative frequency of PA requests and
      their association with payers and medications in order to identify opportunities
      to improve system efficiency. PROCEDURE: Requests for medication PA were logged
      prospectively for patients seen at a single institution over a 7-month period.
      Period prevalence was used to estimate the relative frequency of PA requests.
      Descriptive statistics summarized the relationship among payers, medications, and
      approvals relative to the frequency of PA requests. RESULTS: For the study
      duration of 150 clinic days, there were 5,583 patient visits. A total of 142
      medication PA requests were received resulting in a period prevalence rate of
      2.5% patient visits. Of the 137 medication PA requests with available outcome
      data, 135 (98.5%) were ultimately approved with additional provider efforts. The
      median clinic staff time spent per request was 46 min with an interquartile range
      of 25-80 min. There was striking process heterogeneity among different payers.
      CONCLUSION: Virtually no medication PA request in pediatric hematology and
      oncology (PHO) leads to alterations in care. Medication utilization management
      strategies in PHO fail to provide benefits reported in other areas of medicine
      and have unmeasured negative effects on timeliness of care and parenteral
      psychological/emotional health. There is opportunity for increasing efficiency
      through payer and provider collaboration on the creation of prescribing standards
      for PHO patients.

PMID- 28436208
TI  - Transition of childhood cancer survivors to adult care: The survivor perspective.

PMID- 28436210
TI  - Stereotactic body radiotherapy for pediatric hepatocellular carcinoma with
      central biliary obstruction.
AB  - Here, we present the case of a pediatric patient with newly diagnosed
      hepatocellular carcinoma causing central biliary obstruction and persistently
      elevated bilirubin of 3.0-4.3 mg/dl despite placement of bilateral internal
      external biliary drains. The tumor was not resectable, and the patient was not a
      candidate for liver transplant due to nodal disease, for chemotherapy due to
      hyperbilirubinemia, or for local therapies aside from stereotactic body
      radiotherapy (SBRT). In this report, we discuss the successful use of SBRT in the
      management of this patient, and its role in allowing the patient to become a
      candidate for additional therapies.

PMID- 28436212
TI  - Cross-sectional and longitudinal epidemiological studies of Internet gaming
      disorder: A systematic review of the literature.
AB  - AIM: The diagnostic criteria of Internet gaming disorder (IGD) have been included
      in section III of DSM-5. This study aims to systematically review both cross
      sectional and longitudinal epidemiological studies of IGD. METHODS: All
      publications included in PubMed and PsychINFO up to May 2016 were systematically
      searched to identify cross-sectional studies on prevalence and longitudinal
      studies of IGD. In the process of identification, articles in non-English
      languages and studies focusing solely on the use of gaming were excluded, and
      those meeting the methodological requirements set by this review were included.
      As a result, 37 cross-sectional and 13 longitudinal studies were selected for
      review. RESULTS: The prevalence of IGD in the total samples ranged from 0.7% to
      27.5%. The prevalence was higher among males than females in the vast majority of
      studies and tended to be higher among younger rather than older people in some
      studies. Geographical region made little difference to prevalence. Factors
      associated with IGD were reported in 28 of 37 cross-sectional studies. These were
      diverse and covered gaming, demographic and familial factors, interpersonal
      relations, social and school functioning, personality, psychiatric comorbidity,
      and physical health conditions. Longitudinal studies identified risk and
      protective factors, and health and social consequences of IGD. The natural course
      of IGD was diverse but tended to be more stable among adolescents compared to
      adults. CONCLUSION: Although existing epidemiological studies have provided
      useful data, differences in methodologies make it difficult to compare the
      findings of these studies when drawing consensus. Future international studies
      using reliable and uniform methods are warranted.

PMID- 28436211
TI  - Primary HPV testing verification: A retrospective ad-hoc analysis of screening
      algorithms on women doubly tested for cytology and HPV.
AB  - BACKGROUND: To evaluate human papillomavirus (HPV) testing as a primary screening
      tool, we retrospectively analyzed data comparing (1) HPV testing to the
      algorithms of the ATHENA Study: (2) cytology alone, (3) cytology with ASCUS
      triage in women 25-29 and (4) cotesting >= 30 or (5) cotesting >= 25. METHODS: We
      retrospectively analyzed data from women tested with both cytology and HPV
      testing from 2010 to 2013. Cumulative risk (CR) for CIN3+ was calculated. Crude
      and verification bias adjusted (VBA) sensitivity, specificity, predictive values,
      likelihood ratios, colposcopy rate, and screening test numbers were compared.
      RESULTS: About 15,173 women (25-95, 7.1% <30) had both HPV and cytological
      testing. Nearly 1,184 (8.4%) had biopsies. About 19.4% had positive cytology,
      14.5% had positive HPV. HPV testing unassociated with ASCUS was requested in 40%
      of women <30, versus 84% >=30, with similar HPV16/18 genotyping results (68% vs.
      70%). 84 CIN3+ were detected with the following 3-year cumulative risk (CR) (95%
      confidence interval): HPV+/ASCUS+, 46% (32-66%), HPV+/NILM 30% (15-58%), HPV
      /ASCUS+ 12% (6-23%), and HPV-/NILM 0.8% (0.2-3.6%). HPV had higher specificity
      57% (54-60%) than cotesting >=30 52% (49-55%). HPV sensitivity 78% (69-87%),
      positive 12.3% (9.8-15.3%), negative 97 (96-98%) predictive values, positive 1.8
      (1.6-2.1) and negative likelihood ratios 0.6 (0.5-0.6), were not significantly
      different. Cotesting increased colposcopy rate and doubled testing per CIN3+
      diagnosed. CONCLUSION: While HPV-/NILM cotesting results are associated with low
      CIN3+ risk, HPV testing had similar screening performance to cotesting and to
      cytology alone. Additionally, HPV testing and cytology incur false negatives in
      nonoverlapping subsets of patients. Diagn. Cytopathol. 2017;45:580-586. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28436213
TI  - Bilateral inguinal hernia after axillary-femoral artery bypass effectively
      treated with laparoscopic repair: A case report.
AB  - We report herein our experience with bilateral inguinal hernia surgery for a
      patient who had previously undergone a Y-shaped vascular graft for an abdominal
      aortic aneurysm and then right axillary-bilateral femoral artery bypass surgery.
      Preoperative physical examination and imaging revealed a subcutaneous vascular
      graft passing from the right axilla through the right flank region and branching
      at the lower abdomen to reach the femoral areas on both sides. As repair surgery
      by inguinal incision was considered difficult, we performed laparoscopic surgery.
      Bilateral direct hernia was observed on intraperitoneal observation. Essentially
      no intraperitoneal organ adhesion to the abdominal wall was present, and the
      previous surgery was also confirmed not to have reached the inguinal
      preperitoneal space. Transabdominal preperitoneal repair was therefore performed,
      yielding favorable results.

PMID- 28436214
TI  - A comparison of the cost of primary closure or rectus abdominis myocutaneous flap
      closure of the perineum after abdominoperineal excision.
AB  - AIM: Perineal wound complications following abdominoperineal resection continue
      to be a major challenge. The aim of this study was to compare the clinical
      outcomes and cost of primary closure (PC) and rectus abdominis myocutaneous (RAM)
      flap reconstruction. METHOD: This was a retrospective case review of consecutive
      patients by one surgeon over 11 years. Patient demographics, risk factors,
      operative details and complications were identified. Inpatient and outpatient
      costs were calculated. RESULTS: A total of 31 patients underwent a RAM
      reconstruction and 37 a PC. There were no significant differences in the
      incidence of wound complications or in the overall costs for either method of
      perineal closure. When there were no complications the mean costs were
      significantly higher in the RAM group ($20 948 vs $17 189, P = 0.005), mainly
      because of the longer operating time. However, the costs of perineal wound
      complications were greater in the PC group (8394 vs 25 911, P = 0.012). These
      wounds took longer to heal (median 2 months vs 5.5 months, P = 0.005) and more
      often required a further reconstructive surgical procedure (RAM 0 vs PC 8, P =
      0.006). CONCLUSION: This is the first study reporting on the cost implications of
      PC and RAM flap reconstruction. The overall costs were similar. This implies
      appropriate clinical selection when choosing between procedures. While the RAM
      flap is more expensive to perform, the finding that it decreases the clinical
      severity and cost of perineal wound complications supports its use when there is
      a high risk of perineal wound complications.

PMID- 28436215
TI  - Multilayer Nanofilms via Inkjet Printing for Stabilizing Growth Factor and
      Designing Desired Cell Developments.
AB  - Biologically versatile basic fibroblast growth factor (bFGF), well known for
      roles of signaling molecules between cells and regulating various cellular
      processes, has been proven to utilize specific functionalities. However, the
      remarkable functions are inclinable to dwindle with decrease of bFGFs' activity.
      In nanoscale, developing thin films with intrinsic characteristics of building
      molecules can facilitate handling various materials for desired purposes.
      Fabricating nanofilm and handling sensitive materials without detriment to
      activity via highly productive manufacturing are significant for practical uses
      in the field of biomedical applications. Herein, a multilayered nanofilm
      fabricating system is developed by inkjet printing to incorporate bFGF
      successfully. It is demonstrated that water mixed with glycerol as biological ink
      maintains stability of bFGFs through simulation and experimental study. With
      highly stable bFGFs, the proliferation of human dermal fibroblast is enhanced and
      the undifferentiated state of induced pluripotent stem cell is maintained by the
      controlled release of bFGF.

PMID- 28436216
TI  - Energy-Sensitive Ion- and Cathode-Luminescent Radiation-Beam Monitors Based on
      Multilayer Thin-Film Designs.
AB  - A multilayer luminescent design concept is presented to develop energy-sensitive
      radiation-beam monitors on the basis of colorimetric analysis. Each luminescent
      layer within the stack consists of rare-earth-doped transparent oxides of optical
      quality and a characteristic luminescent emission under excitation with electron
      or ion beams. For a given type of particle beam (electron, protons, alpha
      particles, etc.), its penetration depth and therefore its energy loss at a
      particular buried layer within the multilayer stack depend on the energy of the
      initial beam. The intensity of the luminescent response of each layer is
      proportional to the energy deposited by the radiation beam within the layer, so
      characteristic color emission will be achieved if different phosphors are
      considered in the layers of the luminescent stack. Phosphor doping, emission
      efficiency, layer thickness, and multilayer structure design are key parameters
      relevant to achieving a broad colorimetric response. Two case examples are
      designed and fabricated to illustrate the capabilities of these new types of
      detector to evaluate the kinetic energy of either electron beams of a few kilo
      electron volts or alpha particles of a few mega-electron volts.

PMID- 28436217
TI  - Using Dopants to Tune Oxygen Vacancy Formation in Transition Metal Oxide
      Resistive Memory.
AB  - Introducing dopants is an important way to tailor and improve electronic
      properties of transition metal oxides used as high-k dielectric thin films and
      resistance switching layers in leading memory technologies, such as dynamic and
      resistive random access memory (ReRAM). Ta2O5 has recently received increasing
      interest because Ta2O5-based ReRAM demonstrates high switching speed, long
      endurance, and low operating voltage. However, advances in optimizing device
      characteristics with dopants have been hindered by limited and contradictory
      experiments in this field. We report on a systematic study on how various metal
      dopants affect oxygen vacancy formation in crystalline and amorphous Ta2O5 from
      first principles. We find that isoelectronic dopants and weak n-type dopants have
      little impact on neutral vacancy formation energy and that p-type dopants can
      lower the formation energy significantly by introducing holes into the system. In
      contrast, n-type dopants have a deleterious effect and actually increase the
      formation energy for charged oxygen vacancies. Given the similar doping trend
      reported for other binary transition metal oxides, this doping trend should be
      universally valid for typical binary transition metal oxides. Based on this
      guideline, we propose that p-type dopants (Al, Hf, Zr, and Ti) can lower the
      forming/set voltage and improve retention properties of Ta2O5 ReRAM.

PMID- 28436218
TI  - PTR3: An Instrument for Studying the Lifecycle of Reactive Organic Carbon in the
      Atmosphere.
AB  - We have developed and characterized the novel PTR3, a proton transfer reaction
      time-of-flight mass spectrometer (PTR-TOF) using a new gas inlet and an
      innovative reaction chamber design. The reaction chamber consists of a tripole
      operated with rf voltages generating an electric field only in the radial
      direction. An elevated electrical field is necessary to reduce clustering of
      primary hydronium (H3O+) and product ions with water molecules present in the
      sample gas. The axial movement of the ions is achieved by the sample gas flow
      only. Therefore, the new design allows a 30-fold longer reaction time and a 40
      fold increase in pressure compared to standard PTR-TOF-MS. First calibration
      tests show sensitivities of up to 18000 counts per second/parts per billion and
      volume (cps/ppbv) at a mass resolution of >8000 m/Deltam (fwhm). The new inlet
      using center-sampling through a critical orifice reduces wall losses of low
      volatility compounds. Therefore, the new PTR3 instrument is sensitive to VOC
      typically present in the ppbv range as well as to semivolatile organic compounds
      (SVOC) and even highly oxidized organic molecules (HOMs) present in the parts per
      quadrillion per volume (ppqv) range in the atmosphere.

PMID- 28436219
TI  - Room-Temperature CuI-Catalyzed Amination of Aryl Iodides and Aryl Bromides.
AB  - A general and effective CuI/N',N'-diaryl-1H-pyrrole-2-carbohydrazide catalyst
      system was developed for the amination of aryl iodides and bromides at room
      temperature with good chemoselectivity between -OH and -NH2 groups. Only 5 mol %
      of CuI and ligands was needed in this protocol to effect the amination of various
      aryl bromides and aryl iodides with a wide range of aliphatic and aryl amines
      (1.3 equiv).

PMID- 28436220
TI  - Metal-Free Organocatalytic Oxidative Ugi Reaction Promoted by Hypervalent Iodine.
AB  - We report here a novel IBX-promoted oxidative coupling of primary amines and its
      utilization to Ugi reaction. Advantageously, the reaction could be carried out in
      choline chloride urea as a natural deep eutectic solvent. A range of imines and
      bisamides from pseudo-four-component oxidative Ugi reaction could be synthesized
      under mild and metal-free conditions. Advantageously, the oxidant (IBX) and
      solvent could be recycled up to five times with only a slight loss in activity.

PMID- 28436221
TI  - The Iron Chaperone Protein CyaY from Vibrio cholerae Is a Heme-Binding Protein.
AB  - CyaY is an iron transport protein for iron-sulfur (Fe-S) cluster biosynthetic
      systems. It also transports iron to ferrochelatase that catalyzes insertion of
      Fe2+ into protoporphyrin IX. Here, we find that CyaY has the ability to bind heme
      as well as iron, exhibiting an apparent dissociation constant for heme of 21 +/-
      6 nM. Absorption and resonance Raman spectra revealed that both ferric and
      ferrous forms of heme were bound to an anionic ligand (e.g., tyrosine and/or
      cysteine). Consistent with this, mutagenesis studies showed that Tyr67 and Cys78
      are possible heme ligands of CyaY. The binding of heme to CyaY increased the
      apparent dissociation constant of CyaY for iron from 65.2 to 87.9 MUM. Circular
      dichroism spectra of CyaY suggested that binding of heme to CyaY induces
      rearrangement of aromatic residues. Furthermore, size-exclusion column
      chromatography demonstrated heme-mediated oligomerization of CyaY. These results
      suggest that heme binding induces conformational changes, including
      oligomerization of CyaY, that result in a decrease in the affinity of CyaY for
      iron. Accordingly, the presence of excess heme in cells would lead to modulation
      of Fe-S cluster or heme biosynthesis. This report provides the first description
      of heme dependence of iron transport by CyaY.

PMID- 28436222
TI  - Influence of Nitric Acid on the Helium Ion Radiolysis of Aqueous Butanal Oxime
      Solutions.
AB  - Samples of butanal oxime in aqueous nitric acid solutions have been irradiated
      with the helium ion (4He2+) beam of the CEMHTI (Orleans, France) cyclotron. The
      consumption yield of butanal oxime has been measured by gas chromatography
      coupled with mass spectrometry. Gaseous products (mainly H2 and N2O) have also
      been monitored by micro-gas chromatography. Yields of liquid phase products
      (hydrogen peroxide and nitrous acid) have been determined by colorimetric
      methods. The influence of nitric acid on the radiation chemical behavior of
      butanal oxime depends on the nitric acid concentration. For a low concentration
      (<=0.5 mol L-1) butanal oxime is protected by the nitrate ions, which can
      efficiently scavenge the water radiolysis radicals. For higher concentrations,
      nitrous acid can accumulate in the medium, therefore leading to a strong increase
      of the butanal oxime degradation. The associated mechanism is an autocatalytic
      oxidation of butanal oxime by HNO2.

PMID- 28436223
TI  - Interconnected Hierarchically Porous Fe, N-Codoped Carbon Nanofibers as Efficient
      Oxygen Reduction Catalysts for Zn-Air Batteries.
AB  - Developing porous carbon-based non-precious-metal catalysts for an oxygen
      reduction reaction (ORR) is a suitable approach to significantly reduce the costs
      of fuel cells or metal-air batteries. Herein, interconnected hierarchically
      porous carbon nanofibers simultaneously doped with nitrogen and iron (HP-Fe
      N/CNFs) were fabricated by facile pyrolysis of polypyrrole-coated electrospun
      polystyrene/FeCl3 fibers. The obtained carbon nanofibers have a high specific
      surface area (569.6 m2/g) and large pore volume (1.00 cm3/ g) as well as
      effective doping of N and Fe. Benefiting from the improved mass transfer and
      utilization of active sites attributed to interconnected hierarchical porous
      structures, HP-Fe-N/CNFs display excellent ORR catalytic activity in alkaline
      media, with a comparable onset potential and half-wave potential but superior
      selectivity, stability, and tolerance against methanol to commercial 30 wt %
      Pt/C. Particularly, when applied in an assembled Zn-air battery, HP-Fe-N/CNFs
      outperform 30 wt % Pt/C in power density and long-term stability, explicitly
      showing their promising practical application.

PMID- 28436224
TI  - Multifunctional Hydrogels Prepared by Dual Ion Cross-Linking for Chronic Wound
      Healing.
AB  - The creation of a moist environment and promotion of blood vessel formation are
      critical for wound healing. Sodium alginate (SA) hydrogel, which has good
      biocompatibility and is able to provide a moist environment, has been widely used
      as a wound dressing. However, it lacks antibacterial ability and bioactivities,
      which would facilitate chronic wound healing. On the basis of the gelation
      characteristics of SA and the bioactive hardystonite (HS) bioceramic, we designed
      a unique, bioactive, injectable composite hydrogel through double ion cross
      linking, in which divalent ions, such as Ca2+ and Zn2+ function as cross-linkers;
      Zn2+ also functions as an antibacterial component and as nutrition for wound
      healing, and Si ions play a key role in determining the bioactivity of the
      hydrogel. With the controlled release of divalent ions, such as Ca2+ and Zn2+
      from HS, the gelation process of the composite hydrogel could be efficiently
      controlled. In addition, in vitro results reveal that the composite hydrogel
      stimulated proliferation and migration of both human dermal fibroblasts and human
      umbilical vein endothelial cells, and the in vivo results show that the wound
      healing process is obviously enhanced, and the formation of epithelium and blood
      vessels are evidently advanced. This study indicates the potential of the SA/HS
      hydrogel as a multifunctional injectable wound dressing with the ability to
      inhibit bacterial growth and stimulate angiogenesis and wound healing.

PMID- 28436225
TI  - Watsonianone A from Rhodomyrtus tomentosa Fruit Attenuates Respiratory-Syncytial
      Virus-Induced Inflammation In Vitro.
AB  - Respiratory syncytial virus (RSV) is one of the most common respiratory
      pathogens. Immoderate inflammation plays a great role in causing RSV-induced
      diseases. In the present study, watsonianone A, isolated from the fruit of
      Rhodomyrtus tomentosa (Ait.) Hassk, was found to show a good inhibitory effect on
      RSV-induced NO production, with a half-maximal inhibitory concentration of 37.2
      +/- 1.6 MUM. Enzyme-linked immunosorbent assay and fluorescence quantitative
      polymerase chain reaction analyses indicated that watsonianone A markedly reduced
      both mRNA and protein levels of tumor necrosis factor alpha, interleukin 6, and
      monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells.
      Mechanistically, watsonianone A inhibited nuclear factor kappaB (NF-kappaB)
      activation by suppressing IkappaBalpha phosphorylation. Further analysis revealed
      that watsonianone A activated the thioredoxin system and decreased intracellular
      reactive oxygen species (ROS) levels, which are closely associated with NF-kappaB
      activation in RSV-infected cells. These results reveal that watsonianone A can
      attenuate RSV-induced inflammation via the suppression of ROS-sensitive
      inflammatory signaling.

PMID- 28436226
TI  - Unleashing the Power and Energy of LiFePO4-Based Redox Flow Lithium Battery with
      a Bifunctional Redox Mediator.
AB  - Redox flow batteries, despite great operation flexibility and scalability for
      large-scale energy storage, suffer from low energy density and relatively high
      cost as compared to the state-of-the-art Li-ion batteries. Here we report a redox
      flow lithium battery, which operates via the redox targeting reactions of LiFePO4
      with a bifunctional redox mediator, 2,3,5,6-tetramethyl-p-phenylenediamine, and
      presents superb energy density as the Li-ion battery and system flexibility as
      the redox flow battery. The battery has achieved a tank energy density as high as
      1023 Wh/L, power density of 61 mW/cm2, and voltage efficiency of 91%. Operando X
      ray absorption near-edge structure measurements were conducted to monitor the
      evolution of LiFePO4, which provides insightful information on the redox
      targeting process, critical to the device operation and optimization.

PMID- 28436227
TI  - It Takes Two to Tango-Double-Layer Selective Contacts in Perovskite Solar Cells
      for Improved Device Performance and Reduced Hysteresis.
AB  - Solar cells made from inorganic-organic perovskites have gradually approached
      market requirements as their efficiency and stability have improved tremendously
      in recent years. Planar low-temperature processed perovskite solar cells are
      advantageous for possible large-scale production but are more prone to exhibiting
      photocurrent hysteresis, especially in the regular n-i-p structure. Here, a
      systematic characterization of different electron selective contacts with a
      variety of chemical and electrical properties in planar n-i-p devices processed
      below 180  degrees C is presented. The inorganic metal oxides TiO2 and SnO2, the
      organic fullerene derivatives C60, PCBM, and ICMA, as well as double-layers with
      a metal oxide/PCBM structure are used as electron transport materials (ETMs).
      Perovskite layers deposited atop the different ETMs with the herein applied
      fabrication method show a similar morphology according to scanning electron
      microscopy. Further, surface photovoltage spectroscopy measurements indicate
      comparable perovskite absorber qualities on all ETMs, except TiO2, which shows a
      more prominent influence of defect states. Transient photoluminescence studies
      together with current-voltage scans over a broad range of scan speeds reveal
      faster charge extraction, less pronounced hysteresis effects, and higher
      efficiencies for devices with fullerene compared to those with metal oxide ETMs.
      Beyond this, only double-layer ETM structures substantially diminish hysteresis
      effects for all performed scan speeds and strongly enhance the power conversion
      efficiency up to a champion stabilized value of 18.0%. The results indicate
      reduced recombination losses for a double-layer TiO2/PCBM contact design: First,
      a reduction of shunt paths through the fullerene to the ITO layer. Second, an
      improved hole blocking by the wide band gap metal oxide. Third, decreased
      transport losses due to an energetically more favorable contact, as implied by
      photoelectron spectroscopy measurements. The herein demonstrated improvements of
      multilayer selective contacts may serve as a general design guideline for
      perovskite solar cells.

PMID- 28436228
TI  - An Accelerated Intermolecular Rauhut-Currier Reaction Enables the Total Synthesis
      of (-)-Flueggenine C.
AB  - The first total synthesis of dimeric securinega alkaloid (-)-flueggenine C is
      completed via an accelerated intermolecular Rauhut-Currier (RC) reaction. Despite
      the numerous reports on the total synthesis of monomeric securinegas, the
      synthesis of dimeric securinegas whose monomeric units are connected by a
      putative enzymatic RC reaction has not been reported to date. We have found that
      installation of a nucleophilic functional group at the gamma-position of an enone
      greatly accelerates the rate of the diastereoselective intermolecular RC
      reaction. This discovery enabled an efficient and selective formation of the
      dimeric intermediate which was further transformed to (-)-flueggenine C.

PMID- 28436229
TI  - Mechanistic Pharmacokinetic Modeling of the Bioamplification of Persistent
      Lipophilic Organic Pollutants in Humans during Weight Loss.
AB  - Bioamplification means the liberation of persistent lipophilic organic pollutants
      (PLOPs) into blood from their storage in inert adipose tissue during rapid weight
      loss. Here, using a modified mechanistic pharmacokinetic model, we investigated
      how chemical properties and anthropometric parameters interact to influence the
      bioamplification of various PLOPs in humans. The model succeeds in reproducing
      literature documented weight loss-induced increments in human blood PLOP
      concentrations. We simulated the degree of bioamplification, as characterized by
      the bioamplification factor (BAmF), of hypothetical PLOPs with different
      combinations of partitioning and biotransformation properties at various rates of
      lipid loss. We also investigated how BAmF evolves with the duration of weight
      loss. Results show that bioamplification is expected to occur for any chemical
      with even moderate lipophilicity (log KOW > 2 and log KOA > 6) as long as the
      half-life for metabolic elimination is long relative to the time scale of
      relative lipid loss (e.g., exceeding 104 h in the case of lipid loss of 3 kg
      month-1 with an initial lipid mass of 40 kg). While BAmF of a chemical is time
      variant, whether bioamplification occurs for a chemical or not is independent of
      the duration of weight loss. The successful application of such a simple model
      demonstrates that it is the lipid dynamics that predominantly govern the dynamics
      of PLOPs rather than vice versa.

PMID- 28436230
TI  - Time and relative dimensions in syndromology: Towards endophenotypes in
      neurology, psychiatry and in-between.

PMID- 28436231
TI  - The Utility of Real-Time Quantitative Polymerase Chain Reaction Genotype
      Detection in the Diagnosis of Urinary Tract Infections in Children.
AB  - Urinary tract infections (UTIs) are the most common serious bacterial infection
      in children with significant morbidity with delayed diagnosis. Polymerase chain
      reaction (PCR) is very accurate in detecting bacteria and widely available, but
      has never been evaluated to detect UTIs in children. To assess the utility of PCR
      as a rapid diagnostic tool, we conducted a prospective cohort study of 193 urine
      samples from children younger than 36 months undergoing evaluation for UTI in the
      emergency department over a 10-month period. A quantification cycle (Cq)
      threshold of 26.15 identified all Escherichia coli positive samples with
      sensitivity and specificity of 100% and 99.5%, respectively (95% CI = 71.5%-100%
      and 97.9%-99.5%, respectively). A Cq threshold of 19.03 identified E coli
      infections >100 000 colony forming units/mL with sensitivity and specificity of
      100% (95% CI = 72.2%-100% and 98.6%-100%, respectively). PCR is very accurate in
      diagnosing E coli UTIs in young children and could be useful as a rapid
      diagnostic tool.

PMID- 28436232
TI  - Safety, Performance, and Satisfaction Outcomes in the Operating Room: A
      Literature Review.
AB  - OBJECTIVE: This review of empirical literature focuses on the design of operating
      rooms (ORs) by investigating the physical environmental features of ORs
      associated with patient and staff outcomes. BACKGROUND: Many ORs built more than
      30 years ago remain operational today. However, most are inadequately designed to
      handle the equipment, processes, and people that a contemporary OR needs to
      accommodate. However, the evidence base for designing ORs has been sorely
      lacking, and little guidance exists on how OR design can improve safety and
      performance outcomes. METHOD: A literature search was conducted using PubMed and
      the university's linked databases. The inclusion criteria included peer-reviewed
      journal articles that reported some aspect of the physical environment of ORs
      along with outcomes. The study included empirical studies as well as nonempirical
      best practice papers. RESULTS: This literature review uncovered 211 articles. The
      main themes that emerged include OR design-related factors, ventilation,
      temperature and humidity, acoustical environment, lighting, and materials. Some
      environmental threats to patient safety in the OR include frequent door openings,
      clutter, poor air quality, surface contamination, and noise. Further, staff
      performance and satisfaction were impacted by factors such as the OR layout and
      equipment and furniture ergonomics. CONCLUSION: This literature review provides
      an overview of the research organized into design-focused topic areas to support
      decision-making by architects and designers. This article highlights gaps in the
      research and identifies areas where best practice and design assumptions need to
      be evaluated using rigorous design research.

PMID- 28436233
TI  - Cyclosporine-based immunosuppressive therapy for patients with steroid-resistant
      focal segmental glomerulosclerosis: a meta-analysis.
AB  - OBJECTIVE: Focal segmental glomerulosclerosis (FSGS) is a leading cause of end
      stage kidney disease that requires immunosuppressive treatment as therapy. Few
      studies have been specifically designed to assess the efficacy of cyclosporine
      (CSA) in patients with steroid-resistant FSGS. This study investigated the
      efficacy of CSA-based therapy in steroid-resistant FSGS. METHODS: Medline,
      Cochrane, EMBASE, and Google Scholar databases were searched through April 30,
      2014 using the keywords "cyclosporine", "steroid-resistant", "focal segmental
      glomerulosclerosis", and "FSGS". Studies with an adult and children with steroid
      resistant primary FSGS treated with CSA-based therapy with or without steroid use
      were included. Complete, partial, and overall remission were the primary
      outcomes. Change in proteinuria, serum creatinine, and estimated glomerular
      filtration rate (eGFR) following treatment were secondary outcomes. RESULTS:
      Seven randomized controlled trials with a total of 373 patients were included.
      Five studies were included in the meta-analysis to assess complete, partial, and
      overall remission of FSGS. Compared with other treatments, CSA-based therapy
      resulted in a significantly greater partial remission rate (p = .018), but
      complete (p = .226) or overall remission rate (p = .050). CSA-based therapy also
      resulted in similar change in proteinuria (p = .084), serum creatinine (p =
      .772), and eGFR (p = .155) compared with other therapy. Study limitations
      included small sample size and heterogeneity in age and comparative treatments
      across the studies. CONCLUSIONS: Cyclosporin-based treatments provided a
      significantly better partial remission rate as compared with other therapies.

PMID- 28436234
TI  - Comparison of Hemodynamic Responses in the Prefrontal Cortex According to
      Differences in Self-Efficacy.
AB  - Although self-efficacy has been used extensively in the field of nursing (e.g.,
      as an outcome measure of nursing interventions), its underlying nature is poorly
      understood. Investigation of the relationship between self-efficacy and brain
      activation will help explain the fundamental nature of self-efficacy. In this
      study, we compared prefrontal activation measured with near-infrared spectroscopy
      (NIRS) across 89 undergraduate students categorized into three groups based on
      their General Self-Efficacy Scale scores: low self-efficacy ( n = 59), moderate
      self-efficacy ( n = 17), and high self-efficacy ( n = 13). Changes in the
      hemoglobin levels of the prefrontal cortex (PFC) during a verbal fluency task
      were assessed using two-channel NIRS. Significant differences in the oxygenated
      hemoglobin (oxy-Hb) level of the left PFC (LPFC) were observed via analysis of
      variance. Post hoc Tukey's test showed a significant difference only between low
      self-efficacy and moderate self-efficacy groups. We found a medium between-group
      effect size in the moderate self-efficacy group versus the low self-efficacy
      group for the changes in oxy-Hb levels of the LPFC ( d = .78; 95% confidence
      interval for effect size [0.22, 1.33]). No significant between-group differences
      were observed with respect to changes in the oxy-Hb in the right PFC. The results
      indicate less left prefrontal activation in the low self-efficacy group than in
      the moderate self-efficacy group. These findings provide evidence to support the
      fundamental nature of self-efficacy.

PMID- 28436235
TI  - The Effect of Epidural Analgesia Alone and in Association With Other Variables on
      the Risk of Cesarean Section.
AB  - INTRODUCTION: Epidural analgesia (EA) is the most widespread pharmacologic method
      of labor pain relief. There remains disagreement, however, regarding its adverse
      effects. The objective of this study was to determine the effect of EA
      administration on the risk of cesarean delivery and its causes (e.g., stalled
      labor, risk of loss of fetal well-being, among others) and the degree to which
      this effect may be modulated by mother-, newborn-, and labor-related variables.
      METHOD: A retrospective cohort observational study was conducted including all
      deliveries in a Spanish public hospital between March 2010 and March 2013 ( N =
      2,450; EA = 562, non-EA = 1,888). RESULTS: Risk of a cesarean section was
      significantly increased by EA administration (odds ratio [ OR] = 2.673; p <
      .0001). The percentage of cesarean deliveries due to the risk of loss of fetal
      well-being was significantly higher in the EA (47.8%) versus non-EA group (27.5%;
      OR = 1.739; p = 0.0012,). The EA-associated risk of cesarean section was not
      significantly modified as a function of maternal age or parity, fetal position,
      newborn weight, weeks of gestation, or sedation administration alone. However,
      these variables in combination may increase the risk. We present multivariate
      models for each group that account for these variables, allowing for estimation
      of the risk of a cesarean delivery if EA is administered. CONCLUSION: EA is
      associated with an increased risk of cesarean delivery. Other variables in
      combination (maternal age or parity, fetal position, newborn weight, weeks of
      gestation, or sedation administration) may increase this risk.

PMID- 28436236
TI  - Put two (and two) together to make the most of physical activity and healthy
      nutrition - A longitudinal online study examining cross-behavioural mechanisms in
      multiple health behaviour change.
AB  - Recommendations for physical activity and for fruit and vegetable intake are
      often not translated into action due to deficits in self-regulatory strategies.
      The present study examines the interplay of intention, intergoal facilitation,
      action and coping planning and self-regulation in facilitating physical activity
      and healthy nutrition. In an online study, intentions and behaviours were
      assessed at baseline, intergoal facilitation and planning at 4-week follow-up,
      self-regulation, physical activity and nutrition at 6-month follow-up in a non
      clinical sample. The final sample (n = 711) consisted of 27.2% men, the age
      ranged from 16 to 78 years. Sequential mediations were tested. Intergoal
      facilitation, planning and self-regulation mediated the link from intention to
      physical activity and nutrition; the specific indirect effects were significant.
      Findings suggest that intergoal facilitation and self-regulation can facilitate
      behaviour change, in addition to planning. Cross-behavioural mechanisms might
      facilitate lifestyle change in several domains.

PMID- 28436238
TI  - Neonatal Bacteremia Caused by an Unusual Suspect.

PMID- 28436237
TI  - Bifidobacterium infantis 35624 and other probiotics in the management of
      irritable bowel syndrome. Strain specificity, symptoms, and mechanisms.

PMID- 28436240
TI  - Biotherapeutic potential and mechanisms of action of colchicine.
AB  - Cancer is a clinical situation caused by uncontrolled cell division and is
      responsible for a large number of deaths worldwide. Colchicine is a classical
      antimitotic, tubulin-binding agent (TBA) which is being explored for its
      antitumor activities, although its tubulin-binding ability leads to some toxicity
      toward normal cells proliferation. Colchicine derivatives are considered as
      potent antitumor compounds with less toxicity compared to colchicine. Derivatives
      with substituted functional groups at A-ring (methoxy), B-ring (acetamide) or C
      ring (methoxy) have been synthesized via chemical and microbial routes and show
      modified bioactivities and altered tropolonic functionality. Earlier reports, in
      combination with our group's research findings, suggest that microbial
      biotransformation is an efficient choice for the production of bioactive
      colchicine derivatives. This route has gained significant interest in the mass
      production of regio-specific, cost-effective, safe and eco-friendly derivatives.
      The present review paper critically analyzes and discusses the development and
      application of colchicine derivatives as a potent antitumor molecule and their
      production through a microbial transformation process. The information provided
      in this review might assist in the stimulation of new ideas regarding the
      development of alternative therapeutic agent(s) for cancer treatment.

PMID- 28436239
TI  - Clinical applications of quantitative proteomics using targeted and untargeted
      data-independent acquisition techniques.
AB  - INTRODUCTION: While selected/multiple-reaction monitoring (SRM or MRM) is
      considered the gold standard for quantitative protein measurement, emerging data
      independent acquisition (DIA) using high-resolution scans have opened a new
      dimension of high-throughput, comprehensive quantitative proteomics. These newer
      methodologies are particularly well suited for discovery of biomarker candidates
      from human disease samples, and for investigating and understanding human disease
      pathways. Areas covered: This article reviews the current state of targeted and
      untargeted DIA mass spectrometry-based proteomic workflows, including SRM,
      parallel-reaction monitoring (PRM) and untargeted DIA (e.g., SWATH).
      Corresponding bioinformatics strategies, as well as application in biological and
      clinical studies are presented. Expert commentary: Nascent application of highly
      multiplexed untargeted DIA, such as SWATH, for accurate protein quantification
      from clinically relevant and disease-related samples shows great potential to
      comprehensively investigate biomarker candidates and understand disease.

PMID- 28436241
TI  - Academic Performance and Lifestyle Behaviors in Australian School Children: A
      Cluster Analysis.
AB  - Poor academic performance has been linked with particular lifestyle behaviors,
      such as unhealthy diet, short sleep duration, high screen time, and low physical
      activity. However, little is known about how lifestyle behavior patterns (or
      combinations of behaviors) contribute to children's academic performance. We
      aimed to compare academic performance across clusters of children with common
      lifestyle behavior patterns. We clustered participants (Australian children aged
      9-11 years, n = 284) into four mutually exclusive groups of distinct lifestyle
      behavior patterns, using the following lifestyle behaviors as cluster inputs:
      light, moderate, and vigorous physical activity; sedentary behavior and sleep,
      derived from 24-hour accelerometry; self-reported screen time and diet.
      Differences in academic performance (measured by a nationally administered
      standardized test) were detected across the clusters, with scores being lowest in
      the Junk Food Screenies cluster (unhealthy diet/high screen time) and highest in
      the Sitters cluster (high nonscreen sedentary behavior/low physical activity).
      These findings suggest that reduction in screen time and an improved diet may
      contribute positively to academic performance. While children with high nonscreen
      sedentary time performed better academically in this study, they also accumulated
      low levels of physical activity. This warrants further investigation, given the
      known physical and mental benefits of physical activity.

PMID- 28436242
TI  - Current status of ramucirumab in gastroesophageal adenocarcinoma.
AB  - Outcomes of patients with advanced gastric or gastroesophageal junction
      adenocarcinoma (GEAC) remain poor despite recent advances. The standard of care
      in the management of this disease had not changed much over the past decade. In
      the first line, a platinum containing doublet/triplet is used, while in <20% of
      patients with human epithelial growth factor receptor type 2 overexpressing
      GEACs, trasuzumab can provide a modest advantage. Until recently, no standard
      second-line regimens existed; however, the results of the REGARD and RAINBOW
      trials led to the approval of ramucirumab in the second-line setting. From these
      trials it is clear that paclitaxel and ramucirumab should be used if possible.
      The placement of ramucirumab may become less clear as the data from immune
      oncology trials in GEAC emerge.

PMID- 28436243
TI  - Comparison of the timing of intervention and treatment modality of poor-grade
      aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVES: The timing and modality of intervention in the treatment of poor
      grade aneurysmal subarachnoid haemorrhage (aSAH) has not been defined. The
      purpose of the study is to analyse whether early treatment and type of
      intervention influence the clinical outcomes of poor-grade aSAH patients.
      MATERIAL AND METHODS: Patients with poor-grade aSAH were retrieved. Demographics,
      Fisher grade, radiological characteristics and clinical outcomes were recorded.
      Outcomes were compared using the modified Rankin Scale (mRS), for groups treated
      early within 24 hours of aSAH or later and by clipping or endovascular therapy.
      Multivariate multiple regression model and logistic regression were used to
      assess factors affecting outcomes at discharge in mRS and length of stay.
      RESULTS: The study was conducted on 79 patients. 47 (59%) were treated by
      clipping, 38 (48%) received intervention within 24 hours of aSAH. Patients
      treated <24h had significantly lower mortality (n = 5; 13% vs. n = 14; 37%; p <
      .023), higher rate of 0-3 mRS (n = 22;58% vs. n = 9; 22%; p < .039) and were
      younger (49.5 +/- 6.1 vs. 65.8 +/- 7.4 years; p < .038). There were no
      significant differences in mRS between clipping and endovascular therapy.
      Predictors of length of stay were ICH, MLS, endovascular therapy, location in
      posterior circulation, Fisher grade and time to intervention <24h. Early
      intervention, <24h significantly influenced the favourable results in mRS (0-3);
      (OR 4,14; Cl95% 3.82-4.35). Posterior circulation aneurysms, midline shift and
      intracerebral hematoma were correlated with poor outcomes. CONCLUSIONS: Early
      treatment, within 24 h, of poor-grade aSAH confirmed better clinical outcome
      compared to later aneurysm securement. There was no significant difference
      between clipping and endovascular treatment.

PMID- 28436244
TI  - A systematic review and meta-synthesis of the qualitative literature exploring
      the experiences and quality of life of survivors of a cardiac arrest.
AB  - BACKGROUND: Survival following cardiac arrest and subsequent cardiopulmonary
      resuscitation (CPR) is increasing worldwide, mainly due to greater awareness of
      the symptoms of cardiac events and an increased attention to CPR training.
      Although patient outcomes remain unpredictable and quantitative studies suggest
      that the overall quality of life (QOL) is acceptable, it is valuable to
      synthesise qualitative studies exploring these phenomena in depth, providing a
      deeper knowledge of survivors' experiences and QOL. AIMS: To critically appraise
      and synthesise the qualitative literature on survivors' experiences of a cardiac
      arrest and CPR with the aim of identifying common themes that can inform clinical
      pathways and thereby improve survivor outcomes and QOL. METHODS: A systematic
      review and meta-synthesis of the qualitative literature, using Thomas and
      Harden's framework, and confined to peer-reviewed papers published from 2000 to
      2015, which were identified through database searches of EBSCO, OVID and
      ProQuest. RESULTS: The search produced 204 papers, and of these, seven relevant
      papers were identified for review. Data extraction included setting,
      participants, research design, data collection, analysis and themes. Five
      qualitative themes were identified and were the subject of this meta-synthesis:
      multitude of contrasting feelings; disruption in the continuum of time; new
      reality and psychological challenges; changed body with new limitations; and
      confrontation with death. CONCLUSION: This review provides insights into the
      experiences of survivors' QOL after CPR. Increased knowledge can improve person
      centred care in the immediate and forthcoming care after the event, both in terms
      of planning for discharge and in the future care of people who survive a cardiac
      arrest.

PMID- 28436246
TI  - Histopathologic Changes of Human Vestibular Epithelia in Intralabyrinthine
      Hemorrhage.
AB  - OBJECTIVE: To determine whether intralabyrinthine hemorrhage affects vestibular
      hair cells, dark cells, and transitional cells in human temporal bones. METHODS:
      We examined 9 temporal bone specimens from 9 deceased donors with unilateral
      intralabyrinthine hemorrhage (the hemorrhage group) along with their 9
      contralateral temporal bone specimens without hemorrhage (the control group). We
      estimated the density of type I and type II hair cells in all peripheral
      sensorial organs (including the cristae of the superior, lateral, and posterior
      semicircular canals, as well as the maculae of the saccule and utricle). We also
      estimated the density of dark and transitional cells in the lateral and posterior
      semicircular canals. RESULTS: The loss of type I hair cells in the cristae of the
      superior, lateral, and posterior semicircular canals and in the maculae of the
      saccule and utricle was significantly higher in the hemorrhage group, as compared
      with the control group ( P < .05). The density of type II hair cells in the
      cristae of the superior and posterior canals and in the macula of the saccule
      significantly differed between the hemorrhage group and the control group ( P <
      .05). CONCLUSION: The loss of vestibular hair cells might be the cause of
      vestibular symptoms in patients with intralabyrinthine hemorrhage.

PMID- 28436247
TI  - Effects of Peripheral Vestibular Dysfunction on Dynamic Postural Stability
      Measured by the Functional Reach Test and Timed Up and Go Test.
AB  - OBJECTIVE: To investigate the influence of vestibular function on dynamic
      postural stability assessed by the functional reach test (FRT) and the timed up
      and go test (TUG). STUDY DESIGN: Retrospective study. SETTING: Tertiary referral
      center. SUBJECTS AND METHODS: The FRT and TUG were performed in 399 patients with
      dizziness. The effects of peripheral vestibular dysfunction assessed by the
      caloric test and cervical vestibular evoked myogenic potentials (cVEMPs) to air
      conducted sound (500 Hz, tone burst) on the results of FRT and TUG were analyzed.
      RESULTS: Neither FRT nor TUG scores showed significant differences in relation to
      the results of the caloric test ( P > .3). The FRT scores in patients who showed
      abnormal cVEMP responses on both sides were significantly smaller than those in
      patients who showed normal cVEMP responses ( P < .01). The TUG scores in patients
      who showed abnormal cVEMP responses on both sides were significantly greater than
      those in patients who showed normal cVEMP responses ( P < .05). CONCLUSION: The
      vestibulo-spinal reflex mediated by the saccule and its afferents is one of the
      factors that influence the maintenance of dynamic postural stability as measured
      by FRT and TUG.

PMID- 28436248
TI  - Granisetron plus dexamethasone for prevention of postoperative nausea and
      vomiting in patients undergoing laparoscopic surgery: A meta-analysis.
AB  - Objective This study was designed to compare the effectiveness of granisetron
      plus dexamethasone for preventing postoperative nausea and vomiting (PONV) in
      patients undergoing laparoscopic surgery. Methods We searched the literature in
      the Cochrane Library, PubMed, EMBASE, and CNKI. Results In total, 11 randomized
      controlled trials were enrolled in this analysis. The meta-analysis showed that
      granisetron in combination with dexamethasone was significantly more effective
      than granisetron alone in preventing PONV in patients undergoing laparoscopy
      surgery. No significant differences in adverse reactions (dizziness and headache)
      were found in association with dexamethasone. Conclusion Granisetron in
      combination with dexamethasone was significantly more effective than granisetron
      alone in preventing PONV in patients undergoing laparoscopic surgery, with no
      difference in adverse reactions between the two groups. Granisetron alone or
      granisetron plus dexamethasone can be used to prevent PONV in patients undergoing
      laparoscopic surgery.

PMID- 28436249
TI  - The weapon focus effect is weaker with Black versus White male perpetrators.
AB  - We compared the influence of a weapon's presence on eyewitnesses' memory for a
      White versus a Black male perpetrator. Prior data indicate that unusual objects
      in visual scenes attract attention and that a weapon's effect depends on how
      unusual it seems within the context in which it appears. Therefore, given the
      stereotype linking Black men and weapons, we predicted a weaker weapon focus
      effect with the Black perpetrator. The results of Experiment 1 supported this
      hypothesis using White and Black witnesses. Moreover, in Experiment 2 the weapon
      focus effect became nonsignificant when the Black perpetrator wore a style of
      clothing that is strongly associated with Black men. We propose that observing an
      armed Black perpetrator automatically activates a stereotype linking Black men
      with weapons and crime, which in turn reduces the perceived unusualness of the
      weapon and thus its ability to attract attention.

PMID- 28436250
TI  - Effect of treatment dose reductions in the setting of hand-foot syndrome on
      survival outcomes in patients with metastatic renal cell carcinoma treated with
      vascular endothelial growth factor receptor inhibitors.
AB  - Purpose Hand-foot syndrome is a common dose limiting toxicity of vascular
      endothelial growth factor receptor tyrosine kinase inhibitors used for treatment
      of patients with metastatic renal cell carcinoma. The effect of treatment dose
      reductions, in the context of hand-foot syndrome, on survival outcomes is
      reported. Methods This was a retrospective case series of patients receiving
      vascular endothelial growth factor receptor tyrosine kinase inhibitors from 1
      January 2004 to 31 October 2013. The main outcomes were progression-free and
      overall survival in these patients experiencing hand-foot syndrome and undergoing
      treatment dose reductions. Univariate and multivariate analyses were conducted
      utilizing Kaplan-Meier method and COX Proportional Hazard model with landmark
      analyses at 2 months. Results Of the 120 patients evaluated, treatment dose
      reductions for any reason were required in 68 (56.7%) patients. The most common
      reasons for treatment dose reductions were mucositis, hand-foot syndrome, and
      fatigue. The median progression-free survival and overall survival were
      significantly longer in patients with hand-foot syndrome with or without
      treatment dose reductions as compared to those without hand-foot syndrome.
      Conclusions An improvement in survival outcomes was observed in metastatic renal
      cell carcinoma patients with treatment-associated hand-foot syndrome despite
      treatment dose reductions. These data need validation in a larger cohort to
      confirm the hypothesis that treatment dose reductions in the setting of hand-foot
      syndrome do not negatively impatient survival.

PMID- 28436251
TI  - Sirolimus coating on heparinized stents prevents restenosis and thrombosis.
AB  - The aim of this study was to evaluate the inhibitory effect of sirolimus coating
      on the occurrence of restenosis and thrombosis with heparinized stents. Heparin
      and dopamine were conjugated by chemical bonding and anchored on the stent
      surface by a mussel-inspired adhesion mechanism. Subsequently, sirolimus was
      coated with poly lactic-glycolic acid on the heparinized stent surface. The
      heparin was well attached to the surface, and the surface was smooth after
      sirolimus coating. The smoothness of the surface was maintained after expansion
      of the stent. The amount of sirolimus released from the stent was 67.3% +/- 4.55%
      within 7 days, followed by continual release up to day 28. The proliferation of
      smooth muscle cells was successfully arrested (51.3% +/- 2.25% at 7 days of
      culture) by sirolimus released from the stent. Platelet adhesion was clearly
      prevented in the heparin-coated group (78.0 +/- 8.00/1.8 cm2) compared to that in
      the heparin noncoated group (5.0 +/- 1.00/1.8 cm2). Animal studies showed that
      the heparin and sirolimus-coated stent group had no obvious inflammatory response
      and no change in the fibrin score compared to those in the other groups. However,
      restenosis clearly decreased in the heparin and sirolimus-coated group (12.3% +/-
      3.54%) compared to the bare-metal stent group (27.5% +/- 8.52%) and the heparin
      coated group (25.3% +/- 11.79%). These results suggest that heparinized surface
      based sirolimus coating may be a useful approach for the prevention of restenosis
      and stent thrombosis.

PMID- 28436253
TI  - Corrigendum.

PMID- 28436252
TI  - Cost-effectiveness and safety of ramucirumab plus paclitaxel chemotherapy in the
      treatment of advanced and recurrent gastric cancer.
AB  - Introduction Weekly paclitaxel (PTX), irinotecan (CPT-11) and ramucirumab plus
      paclitaxel (Ram + PTX) are currently recommended as the standard second-line or
      later chemotherapies for advanced and recurrent gastric cancer. This study aims
      to compare the cost-effectiveness of using Ram + PTX vs. PTX or CPT-11.
      Furthermore, we investigated the safety and treatment continuity of Ram + PTX in
      Japan. Methods Expected costs were calculated based on data from patients with
      advanced and recurrent gastric cancer who were treated with PTX, CPT-11 and Ram +
      PTX. A literature review was performed to obtain clinical information so that the
      probability of the efficacy of each chemotherapy could be calculated. The cost
      effectiveness ratio of each chemotherapy agent was calculated by dividing the
      expected cost by the median survival time (MST). Results The cost-effectiveness
      ratio per month was JPY 85,395.8/MST for the PTX regimen, JPY 132,735.4/MST for
      the CPT-11 regimen and JPY 657,175.4/MST for the Ram + PTX regimen (p < 0.001).
      The incremental cost-effectiveness ratio per month of the Ram + PTX regimen to
      the PTX regimen was JPY 2,780,432.4/MST. The incremental cost-effectiveness ratio
      of the Ram + PTX regimen to the CPT-11 regimen was JPY 2,185,179.0/MST. With
      regard to the reasons for discontinuation of treatment, the Ram + PTX regimen had
      only one case of being discontinued owing to adverse events, and had a profile
      similar to that of the PTX and CPT-11 regimens. Conclusion These findings show
      that the Ram + PTX regimen is less cost-effective compared to both the PTX and
      CPT-11 regimen, but the Ram + PTX regimen is a well-tolerated regimen with
      sufficient efficacy.

PMID- 28436254
TI  - The correlation between histological gastritis staging- 'OLGA/OLGIM' and serum
      pepsinogen test in assessment of gastric atrophy/intestinal metaplasia in China.
AB  - BACKGROUND: Serum pepsinogen (PG) test, as an indicator of gastric mucosal
      atrophy, reflects the functional and morphologic status of gastric mucosal and it
      is suggested to serve as a useful predictive marker for patients with gastric
      cancer (GC). The available classifications of gastritis, known as the Operative
      Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal
      Metaplasia (OLGIM), integrating the severity and topography of atrophy/intestinal
      metaplasia (IM), have been gradually accepted and used in screening for GC in
      recent years. GOALS: To assess whether serum pepsinogen test, including PGI,
      PGII, PGI/PGII and gastrin-17 (G-17) could reflect the extent and topography of
      gastric mucosal atrophy/IM. Furthermore, to discuss the relationship between
      OLGA/OLGIM staging system and serum pepsinogen test in assessment of gastric
      atrophy/IM. METHODS: The OLGA/OLGIM ranks the gastric staging according to both
      the topography and the severity of gastric atrophy/IM. A retrospective study was
      conducted with 331 patients who underwent endoscopy with consecutive biopsy
      sampling and reassessed according to OLGA/OLGIM staging system. Serum pepsinogen
      test, including PGI, PGII, PGI/PGII and G-17, as well as serological Helicobacter
      pylori (Hp) antibody were also measured. Results were presented as gastritis
      stage, serum pepsinogen level and Hp status. Baseline characteristics were
      compared using analysis of variance (ANOVA) test for continuous data and
      Pearson's chi2 test for categorical data. A logistic regression model was used
      for the correlation analysis between OLGA/OLGIM and serological pepsinogen test.
      RESULTS: A total of 177 non-atrophic gastritis and 154 atrophic gastritis were
      analyzed, among which 40 were antrum atrophy, 32 were corpus atrophy and 82 were
      pan-atrophy. All patients were assessed applying the OLGA/OLGIM criteria with a
      mean age of 54.7 +/- 10.8 years. Patients among OLGA/OLGIM Stage III-IV were
      presented with a lower level of serum PGI and PGI/PGII (p < .05), especially for
      Stage IV (p = .01). For both Hp-positive patients and Hp-negative patients
      according to OLGA system, PGI/PGII level correlated inversely with the rising
      stage (p = .022; p = .028). As for OLGIM system, similar difference can be seen
      in PGI/PGII level in either Hp-positive patients, or Hp-negative patients (p =
      .036; p = .013). In addition, the percentage of G-17 <1 pmol/L combined with PG
      negative in antrum atrophy group was much higher than that of non-atrophy group
      and corpus atrophy group (25 versus 15.8 versus 6.3%) (p = .029). The proportion
      of G-17 > 15 pmol/L combined with PG-positive was apparently higher in corpus
      atrophy group, compared with other two groups (25 versus 11.3 versus 8.1%) (p =
      .023). Logistic regression modeling showed there exist significant connections
      between OLGA/OLGIM stages and serum pepsinogen test in patient stratification for
      gastric mucosal atrophy assessment (p < .001, p < .001). CONCLUSIONS: Serum
      pepsinogen test has a strong correlation with OLGA/OLGIM gastritis stage and
      could provide important information in assessment of atrophy/intestinal
      metaplasia.

PMID- 28436255
TI  - Detection and characterization of small infarcts in the caudate nucleus on 7
      Tesla MRI: The SMART-MR study.
AB  - Small infarcts are among the key imaging features of cerebral small vessel
      disease (CSVD), but remain largely undetected on conventional MRI. We aimed to
      evaluate (1) imaging criteria for the detection of small infarcts in the caudate
      nucleus on 7T MRI, (2) intra- and inter-rater agreement, (3) frequency and (4)
      detection rate on 7T versus 1.5T MRI. In 90 patients (68 +/- 8 years) with a
      history of vascular disease from the SMART-MR study, we defined 7T imaging
      criteria for cavitated and non-cavitated small infarcts in the caudate nucleus.
      In a separate set of 23 patients from the SMART study, intra-rater and inter
      rater agreement was excellent for presence, number, and individual locations
      (Kappa's, ICCs, and Dice similarity coefficients ranged from 0.85 to 1.00). In
      the 90 patients, 21 infarcts (20 cavitated) in 12 patients were detected on 7T
      (13%) compared to 7 infarcts in 6 patients on 1.5T (7%). In conclusion, we
      established reproducible imaging criteria for the detection of small infarcts in
      the caudate nucleus on 7T MRI and showed that 7T MRI allows for a higher
      detection rate than conventional 1.5T MRI. These imaging criteria can be used in
      future studies to provide new insights into the pathophysiology of CSVD.

PMID- 28436256
TI  - Clinical and Economic Impact of Hyperkalemia in Patients with Chronic Kidney
      Disease and Heart Failure.
AB  - BACKGROUND: Hyperkalemia (HK) is a concern for patients with chronic kidney
      disease (CKD) and heart failure (HF), and for those receiving treatments that
      inhibit the renin-angiotensin-aldosterone system (RAASi). An analysis of 1.7
      million medical records of patients in the United States revealed that among
      individuals with more than 2 potassium values during 2007 to 2012, HK was
      detected in 34.6% of patients with CKD and 30.0% of patients with HF. OBJECTIVE:
      To evaluate the association of HK and use of RAASi therapies at optimal and
      suboptimal doses in patients with CKD and/or HF with health care resource
      utilization and overall cost of care in a diverse cohort of commercially insured
      patients. METHODS: This retrospective cohort study was conducted using medical
      and pharmacy claims from multiple regional health plans. Qualifying patients were
      >= 18 years old, continuously enrolled for 6 months before and throughout the
      study period (January 1, 2014, to December 31, 2015) and had an ICD-9-CM or ICD
      10-CM diagnosis code of CKD and/or HF. Health care resource utilization,
      including hospital visits, length of stay, office visits, and associated medical
      and pharmacy costs, were assessed according to the 3 cohorts (CKD alone, HF
      alone, and concomitant CKD and HF). For the 3 cohorts, the results were also
      compared between patients with and without HK and between patients with and
      without RAASi use at optimal and suboptimal doses. Generalized linear models were
      used to further examine the predictors of medical and overall costs. RESULTS: In
      this study, 15,999 patients met inclusion criteria. Among patients using RAASi
      therapy, 26.8% received the optimal dose. Optimal dosing of RAASi was associated
      with decreased median outpatient office visits (8, 10, and 15, respectively, for
      patients with CKD, HF, and both CKD and HF) compared with suboptimal dosing of
      RAASi (12, 15, and 23, respectively). Similarly, optimal dosing of RAASi was
      associated with decreased overall median medical costs ($2,092, $4,144, and
      $7,762, respectively, for patients with CKD, HF, and both CKD and HF) compared
      with suboptimal dosing of RAASi ($3,121, $8,289, and $12,749, respectively).
      Patients with CKD, HF, or both CKD and HF, all in combination with HK, had higher
      overall costs, compared with those without HK. CONCLUSIONS: The results of this
      real-world analysis suggest that HK and suboptimal dosing of RAASI were
      associated with a median increase in outpatient office visits as well as
      increased overall medical costs among patients with CKD and/or HF. This
      evaluation of median costs suggests effective HK management may potentially
      reduce costs in patients with CKD and/or HF, including those currently receiving
      RAASi therapy. DISCLOSURES: This study was conducted by Magellan Rx Management
      and funded by Relypsa. Brenner, Alvarez, and Oestreicher were employed by Relypsa
      during the development of this study and the writing of this manuscript. Polson,
      Lord, Kangethe, Speicher, and Farnum are employees of Magellan Rx Management,
      which received funding from Relypsa for conducting the retrospective study and
      writing the manuscript. Study concept and design were contributed by Lord,
      Polson, Brenner, Alvarez, and Oestreicher. Data collection and interpretation
      were performed by Polson and Kangethe, with assistance from Lord. The manuscript
      was written by Farnum, with assistance from Kangethe and Speicher and revised by
      all authors.

PMID- 28436258
TI  - Thrombopoietin and platelet aggregation in patients with stable coronary artery
      disease.
AB  - Thrombopoietin (TPO) may facilitate platelet activation and aggregation. However,
      data on the impact of TPO on platelet aggregation in patients with stable
      coronary artery disease (CAD) are scarce. We aimed to investigate associations
      between TPO and platelet aggregation and activation in patients with stable
      coronary artery disease (CAD). We studied 900 stable CAD patients. Serum TPO was
      assessed by ELISA. Platelet aggregation was evaluated using the Multiplate
      Analyzer (agonists: arachidonic acid [AA] and collagen) and the VerifyNow Aspirin
      Assay. Platelet activation was evaluated by soluble (s)P-selectin. Cyclooxygenase
      1 inhibition was evaluated by serum thromboxane B2 (TXB2). We found that TPO
      correlated weakly with platelet aggregation evaluated by Multiplate using AA (r =
      -0.09, p = 0.01) and collagen as agonists (r = -0.03, p = 0.43) and by VerifyNow
      (r = 0.07, p = 0.03). We found no correlation between TPO and sP-selectin (r = 
      0.01, p = 0.70). Independent predictors of AA-induced platelet aggregation by
      Multiplate included high levels of sP-selectin and serum TXB2, high platelet
      count, increasing age and body mass index, female sex, and active smoking.
      Independent predictors of TPO included low AA-induced platelet aggregation by
      Multiplate, high levels of hs-CRP, active smoking, and high platelet aggregation
      evaluated by VerifyNow. In conclusion, TPO levels did not correlate with platelet
      activation and only weak associations were found between TPO and platelet
      aggregation, suggesting that TPO did not substantially facilitate platelet
      aggregation in stable CAD patients.

PMID- 28436257
TI  - Brain temperature but not core temperature increases during spreading
      depolarizations in patients with spontaneous intracerebral hemorrhage.
AB  - Spreading depolarizations (SDs) are highly active metabolic events, commonly
      occur in patients with intracerebral hemorrhage (ICH) and may be triggered by
      fever. We investigated the dynamics of brain-temperature (Tbrain) and core
      temperature (Tcore) relative to the occurrence of SDs. Twenty consecutive
      comatose ICH patients with multimodal electrocorticograpy (ECoG) and Tbrain
      monitoring of the perihematomal area were prospectively enrolled. Clusters of SDs
      were defined as >=2 SDs/h. Generalized estimating equations were used for
      statistical calculations. Data are presented as median and interquartile range.
      During 3097 h (173 h [81-223]/patient) of ECoG monitoring, 342 SDs were analyzed
      of which 51 (15%) occurred in clusters. Baseline Tcore and Tbrain was 37.3C (36.9
      37.8) and 37.4C (36.7-37.9), respectively. Tbrain but not Tcore significantly
      increased 25 min preceding the onset of SDs by 0.2C (0.1-0.2; p < 0.001) and
      returned to baseline 35 min following SDs. During clusters, Tbrain increased to a
      higher level (+0.4C [0.1-0.4]; p = 0.006) when compared to single SDs. A higher
      probability (OR = 36.9; CI = 36.8-37.1; p < 0.001) of developing SDs was observed
      during episodes of Tbrain >= 38.0C (23% probability), than during Tbrain <= 36.6C
      (9% probability). Spreading depolarizations - and in particular clusters of SDs -
      may increase brain temperature following ICH.

PMID- 28436261
TI  - A qRT-PCR and Gene Functional Enrichment Study Focused on Downregulation of miR
      141-3p in Hepatocellular Carcinoma and Its Clinicopathological Significance.
AB  - BACKGROUND: The clinical significance of miR-141-3p in hepatocellular carcinoma
      has not been verified. Therefore, we conducted this study to examine miR-141-3p
      expression and its clinical significance in hepatocellular carcinoma and to
      investigate the functions of its potential targets. METHODS: The Cancer Genome
      Atlas database and the Gene Expression Omnibus database were used to explore the
      aberrant expression of miR-141-3p in hepatocellular carcinoma. Furthermore, we
      assessed the miR-141-3p levels in 95 hepatocellular carcinoma tissues with 95
      matched adjacent tissues using real-time quantitative polymerase chain reaction.
      Moreover, a target gene prediction analysis of miR-141-3p, a natural language
      processing analysis for hepatocellular carcinoma using PubMed, and a gene
      functional enrichment analysis were conducted to search the potential function of
      miR-141-3p in the pathogenesis of hepatocellular carcinoma. RESULTS: Regarding
      The Cancer Genome Atlas data, miR-141-3p levels were markedly downregulated in
      hepatocellular carcinoma tissue compared to para- or nontumor tissue (4.6112
      [1.7096] vs 5.3053 [1.4254], P = .045). MiR-141-3p expression was reduced in
      patients with hepatocellular carcinoma with a low pathologic T stage ( P = .006),
      a low grade ( P = .01), elderly hepatocellular carcinoma patients ( P = .001),
      and male patients with hepatocellular carcinoma ( P = .01) compared with that in
      patients with hepatocellular carcinoma with high pathologic T stages, high
      grades, young patients with hepatocellular carcinoma, and female patients with
      hepatocellular carcinoma. However, according to the Gene Expression Omnibus
      database, no significant differences in the expression of miR-141-3p were
      observed between hepatocellular carcinoma tissue and normal liver tissue ( P =
      .984). Real-time quantitative polymerase chain reaction confirmed a similar trend
      of decreased miR-141-3p in hepatocellular carcinoma tissue (1.7542 [0.8663] vs
      2.5562 [1.7913], P = .001) as observed in The Cancer Genome Atlas. In addition,
      decreased miR-141-3p levels were detected in the multiple tumor nodes group ( P =
      .004), the metastasis group ( P < .001), and the advanced TNM stage group ( P =
      .01), compared to the single tumor nodes group, the nonmetastasis group, and the
      early TNM stage group. Two hundred eighty-two genes were identified from the
      overlap between the predicted targets and the natural language processing
      analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway
      analyses revealed several significant biological functions and pathways related
      to the pathogenesis of cancers, including hepatocellular carcinoma. CONCLUSION:
      Downregulation of miR-141-3p might be responsible for the carcinogenesis and
      aggressiveness of hepatocellular carcinoma. MiR-141-3p may act as an antitumor
      microRNA, which is essential for hepatocellular carcinoma progression through the
      regulation of various signaling pathways. Thus, interactions with miR-141-3p may
      provide a novel strategy for hepatocellular carcinoma treatment in the future.

PMID- 28436262
TI  - Private Philanthropy and Basic Research in Mid-Twentieth Century America: The
      Hickrill Chemical Research Foundation.
AB  - The Hickrill Chemical Research Foundation, located north of New York City on the
      estate of its patrons, Sylvan and Ruth Alice Norman Weil, had a short (1948-59)
      but productive life. Ruth Alice Weil received a Ph.D. in organic chemistry in
      1947, directed by William von Eggers Doering of Columbia University. She intended
      that Hickrill contribute to cancer chemotherapy while providing resources for
      Doering's more speculative research. Ultimately, Doering's commitment to
      theoretical organic chemistry set Hickrill's research agenda. Lawrence Knox, an
      African American with a Harvard Ph.D., supervised the laboratory's daily
      activities. Hickrill's two dozen postdoctoral fellows produced path-breaking
      results in Huckel aromatic theory and reactive intermediate chemistry, fostering
      the postwar emphasis on "basic science." This essay places the Laboratory's
      successes in the wider context of postwar politics and scientific priorities.
      Private philanthropic support of basic science arose because it received little
      pre-World War II government support. In the immediate postwar period, modest
      organisations like Hickrill still met a need, but the increasing governmental
      defence- and non-defence-related support for science eventually rendered them
      unnecessary.

PMID- 28436263
TI  - Modern Methods for Modeling Change in Obesity Research in Nursing.
AB  - Persons receiving treatment for weight loss often demonstrate heterogeneity in
      lifestyle behaviors and health outcomes over time. Traditional repeated measures
      approaches focus on the estimation and testing of an average temporal pattern,
      ignoring the interindividual variability about the trajectory. An alternate
      person-centered approach, group-based trajectory modeling, can be used to
      identify distinct latent classes of individuals following similar trajectories of
      behavior or outcome change as a function of age or time and can be expanded to
      include time-invariant and time-dependent covariates and outcomes. Another latent
      class method, growth mixture modeling, builds on group-based trajectory modeling
      to investigate heterogeneity within the distinct trajectory classes. In this
      applied methodologic study, group-based trajectory modeling for analyzing changes
      in behaviors or outcomes is described and contrasted with growth mixture
      modeling. An illustration of group-based trajectory modeling is provided using
      calorie intake data from a single-group, single-center prospective study for
      weight loss in adults who are either overweight or obese.

PMID- 28436264
TI  - Interventions to Improve Grandparent Caregivers' Mental and Physical Health: An
      Integrative Review.
AB  - The aim of this integrative review is to appraise grandparent caregiver
      interventions that are designed to improve their physical and mental health. A
      database search was performed to identify relevant studies published between
      January 1, 1980, and December 31, 2014. Thirteen publications, including 11
      studies, met all inclusion and exclusion criteria. All studies included
      grandparent mental health outcomes with fewer focusing on physical health and
      social relations. Improvements were found in all three areas with fewer
      improvements seen in physical health. However, small effect sizes were seen with
      most measures of these outcomes. Although the interventions led to positive
      grandparent caregiver outcomes, the studies were limited by their design, only
      one of which was a randomized controlled trial. Also, interventions did not
      consider variations in the grandchild's or parent's ages or if the grandparent
      provided primary or shared care. These gaps should be addressed in future
      research.

PMID- 28436265
TI  - Recruiting African American Children for Research: An Ecological Systems Theory
      Approach.
AB  - With health disparities still pervasive and persistent in the United States,
      medical researchers and social scientists continue to develop recruitment
      strategies to increase the inclusion of racial/ethnic minority groups in research
      and interventions. Effective methods for recruiting samples of African American
      participants for pediatric research may be best understood when situated within
      an overarching conceptual model-one that serves to organize and explain effective
      recruitment strategies. A theoretical framework well suited for this purpose is
      Bronfenbrenner's ecological systems theory, which views individuals as
      influencing and being influenced by (both directly and indirectly) a series of
      interconnected social systems. Based on the ecological systems theory and on
      previous research from multiple domains (e.g., medicine, psychology, public
      health, social work), in the current article, we review strategies for effective
      recruitment of African American children and adolescents for research.

PMID- 28436266
TI  - The Identity Threat of Weight Stigma in Adolescents.
AB  - Obesity remains a serious public health issue in adolescents, who may be
      subjected to weight stigma leading to increased stress and poor health outcomes.
      Stigma can be detrimental to adolescents during self-identity formation. The
      purpose of this study was to examine weight stigma in adolescents in light of the
      Identity Threat Model of Stigma. A cross-sectional correlational design was used
      to examine the relationships among the variables of weight stigma, psychosocial
      stress, coping styles, disordered eating, and physical inactivity. Regression
      modeling and path analysis were used to analyze the data. Over 90% of the sample
      had scores indicating weight stigma or antifat bias. Avoidant coping style and
      psychosocial stress predicted disordered eating. The strongest path in the model
      was from avoidant coping to disordered eating. The Identity Threat Model of
      Stigma partially explained adolescents' weight stigma. Nursing practice
      implications are discussed.

PMID- 28436267
TI  - Pneumonia with pleural empyema caused by Salmonella Typhi in an immunocompetent
      child living in a non-endemic country.
AB  - Extra-intestinal complications of Salmonella Typhi (S. Typhi) infections usually
      occur in endemic countries and in patients with underlying risk conditions. A 14
      year-old immunocompetent girl was admitted with respiratory distress owing to S.
      Typhi pneumonia and pleural empyema. She was a native of Ivory Coast but had
      lived in France for 4 years and had not travelled abroad for several years. There
      were no gastro-intestinal symptoms and no S. Typhi carriage was detected in her
      family. She recovered completely with ceftriaxone and ciprofloxacin and pleural
      drainage was not required. An atypical presentation of S. Typhi should be
      considered even in settings where there are no risk factors.

PMID- 28436268
TI  - Collateral circulation alters downstream hemodynamic stress caused by
      intracranial atherosclerotic stenosis.
AB  - OBJECTIVES: Fractional flow reserve (FFR) accurately predicts the degree of
      stenosis and is now widely used to identify clinically significant severe
      coronary artery lesions. In the current study, we utilized a similar indicator,
      fractional flow (FF), to determine the hemodynamic impact of symptomatic
      intracranial atherosclerotic stenosis (ICAS) and to assess the correlation of FF
      with the severity of stenosis and collateral circulation. METHODS: Patients with
      symptomatic ICAS (70-99% stenosis) confirmed on digital subtraction angiography
      (DSA) were consecutively recruited. FF was obtained during DSA examination with
      the use of pressure sensors and was measured as a ratio, comparing measurements
      distal to an ICAS lesion (Pd) and within the aorta (Pa). The degree of
      leptomeningeal collateralization was graded from zero (absent) to four (complete
      compensatory). The correlation between FF, anatomical stenosis, and collateral
      status was then analyzed. RESULTS: Twenty-five patients with a mean age of 55.6
      years were analyzed. The median percentage of stenosis and median FF were 82.3
      and 0.68%, respectively. Eleven patients were found to have poor
      collateralization (grade 0-2), and fourteen patients were identified with good
      collateral circulation (grade 3-4). Overall, the hemodynamic impact of an
      atherosclerotic lesions worsened (decreased FF) as the percentage of stenosis
      increased, although this did not reach statistical significance (r = -0.398, p =
      0.06). However, the status of collateralization significantly altered this
      correlation, worsening the hemodynamic impact in patients with poor collateral
      circulation (r = -0.677, p = 0.032). There was no difference in patients with
      good collateral circulation (r = -0.279, p = 0.356). CONCLUSION: An anatomically
      severe (70-99%) symptomatic ICAS lesion may generate significant hemodynamic
      stress downstream as assessed by the indicator FF, particularly in patients with
      poor collateral circulation. Further, good collateralization may mitigate this
      hemodynamic impact, partially explaining the protective effect of collateral
      circulation against recurrent stroke in such patients.

PMID- 28436269
TI  - An Evaluation of Single-Case Reading Intervention Study Quality for Students With
      and At Risk for Emotional and Behavioral Disorders.
AB  - Researchers have noted the lack of research to guide reading practice for
      students with and at risk for emotional and behavioral disorders (EBD). Although
      comprehensive syntheses have identified promising practices and areas for future
      research, none have evaluated the rigor of studies according to quality
      indicators. The current study evaluated the extant single-case reading
      intervention research for this student population according to the What Works
      Clearinghouse (WWC) standards. Thirty studies met article selection criteria, 20
      (66.6%) of which had at least one dependent variable that did not meet design
      standards. Study findings suggest a need for researchers to employ stronger
      designs and place a greater emphasis on investigating the effects of reading
      instructional practices in inclusive settings. Overall, two reading interventions
      were identified as potentially promising: cognitive mapping and a listening while
      reading accommodation. Furthermore, findings suggest that it may be advantageous
      to embed behavioral strategies within reading interventions. Study limitations
      include the exclusive use of single-case design studies and a reliance on visual
      analysis to determine intervention effectiveness.

PMID- 28436270
TI  - Does Physiological Stress Slow Down Wound Healing in Patients With Diabetes?
AB  - BACKGROUND: Poor healing is an important contributing factor to amputation among
      patients with diabetic foot ulcers (DFUs). Physiological stress may slow wound
      healing and increase susceptibility to infection. OBJECTIVES: The objective was
      to examine the association between heart rate variability (HRV) as an indicator
      of physiological stress response and healing speed (HealSpeed) among outpatients
      with active DFUs. DESIGN AND METHODS: Ambulatory patients with diabetes with DFUs
      (n = 25, age: 59.3 +/- 8.3 years) were recruited. HRV during pre-wound dressing
      was measured using a wearable sensor attached to participants' chest. HRVs were
      quantified in both time and frequency domains to assess physiological stress
      response and vagal tone (relaxation). Change in wound size between two
      consecutive visits was used to estimate HealSpeed. Participants were then
      categorized into slow healing and fast healing groups. Between the two groups,
      comparisons were performed for demographic, clinical, and HRV derived parameters.
      Associations between different descriptors of HRV and HealSpeed were also
      assessed. RESULTS: HealSpeed was significantly correlated with both vagal tone (
      r = -.705, P = .001) and stress response ( r = .713, P = .001) extracted from
      frequency domain. No between-group differences were observed except those from
      HRV-derived parameters. Models based on HRVs were the highest predictors of
      slow/fast HealSpeed (AUC > 0.90), while models based on demographic and clinical
      information had poor classification performance (AUC = 0.44). CONCLUSION: This
      study confirms an association between stress/vagal tone and wound healing in
      patients with DFUs. In particular, it highlights the importance of vagal tone
      (relaxation) in expediting wound healing. It also demonstrates the feasibility of
      assessing physiological stress responses using wearable technology in outpatient
      clinic during routine clinic visits.

PMID- 28436271
TI  - Divided attention enhances the recognition of emotional stimuli: evidence from
      the attentional boost effect.
AB  - The present study examined predictions of the early-phase-elevated-attention
      hypothesis of the attentional boost effect (ABE), which suggests that transient
      increases in attention at encoding, as instantiated in the ABE paradigm, should
      enhance the recognition of neutral and positive items (whose encoding is mostly
      based on controlled processes), while having small or null effects on the
      recognition of negative items (whose encoding is primarily based on automatic
      processes). Participants were presented a sequence of negative, neutral and
      positive stimuli (pictures in Experiment 1, words in Experiment 2) associated to
      target (red) squares, distractor (green) squares or no squares (baseline
      condition). They were told to attend to the pictures/words and simultaneously
      press the spacebar of the computer when a red square appeared. In a later
      recognition task, stimuli associated to target squares were recognised better
      than stimuli associated to distractor squares, replicating the standard ABE. More
      importantly, we also found that: (a) the memory enhancement following target
      detection occurred with all types of stimuli (neutral, negative and positive) and
      (b) the advantage of negative stimuli over neutral stimuli was intact in the DA
      condition. These findings suggest that the encoding of negative stimuli depends
      on both controlled (attention-dependent) and automatic (attention-independent)
      processes.

PMID- 28436272
TI  - Moderation of the effects of discrimination-induced affective responses on health
      outcomes.
AB  - OBJECTIVE: The goal of the study was to examine differential mediation of long
      term effects of discrimination on health behaviour and health status by
      internalising (anxiety and depression) and externalising (hostility and anger),
      and to explore moderation of these effects, specifically, by the presence of
      support networks and coping tendencies. DESIGN: The current analyses employed
      structural equation modelling of five waves of data from Black female
      participants of the Family and Community Health Study over 11 years (M age 37
      48). MAIN OUTCOMES MEASURES: The main outcome variables were health status and
      alcohol use (frequency and problematic consumption). RESULTS: Perceived racial
      discrimination was associated with increases in internalising and externalising.
      In addition, internalising reactions to discrimination were associated with
      deterioration in health status and increases in problematic drinking;
      externalising reactions were associated with increases in frequency of drinking.
      These relations were attenuated by availability of support networks, and
      exacerbated by use of avoidance coping. CONCLUSION: The current study (a)
      replicated previous research suggesting that two different types of affective
      reactions mediate the relations between perceived racial discrimination and
      physical health status vs. health-impairing behaviours: internalising and
      externalising, and (b) revealed moderation of these effects by coping mechanisms.

PMID- 28436273
TI  - Proteome analysis of sheep B lymphocytes in the course of bovine leukemia virus
      induced leukemia.
AB  - Presented are the results of a study of the expression pattern of different
      proteins in the course of bovine leukemia virus-induced leukemia in experimental
      sheep and I discuss how the obtained data may be useful in gaining a better
      understanding of the pathogenesis of the disease, diagnosis, and for the
      selection of possible therapeutic targets. In cattle, the disease is
      characterized by life-long persistent lymphocytosis leading to leukemia/lymphoma
      in about 5% of infected animals. In sheep, as opposed to cattle, the course of
      the disease is always fatal and clinical symptoms usually occur within a three
      year period after infection. For this reason, sheep are an excellent experimental
      model of retrovirus-induced leukemia. This model can be useful for human
      pathology, as bovine leukemia virus is closely related to human T-lymphotropic
      virus type 1. The data presented here provide novel insights into the molecular
      mechanisms of the bovine leukemia virus-induced tumorigenic process and indicate
      the potential marker proteins both for monitoring progression of the disease and
      as possible targets of pharmacological intervention. A study of the proteome of B
      lymphocytes from four leukemic sheep revealed 11 proteins with altered
      expression. Among them, cytoskeleton and intermediate filament proteins were the
      most abundant, although proteins belonging to the other functional groups, i.e.
      enzymes, regulatory proteins, and transcription factors, were also present. It
      was found that trypsin inhibitor, platelet factor 4, thrombospondin 1,
      vasodilator-stimulated phosphoprotein, fibrinogen alpha chain, zyxin, filamin-A,
      and vitamin D-binding protein were downregulated, whereas cleavage and
      polyadenylation specificity factor subunit 5, non-POU domain-containing octamer
      binding protein and small glutamine-rich tetratricopeptide repeat-containing
      protein alpha were upregulated. Discussed are the possible mechanisms of their
      altered expression and its significance in the bovine leukemia virus-induced
      leukemogenic process. Impact statement The submitted manuscript provides new data
      on the molecular mechanisms of BLV-induced tumorigenic process indicating the
      potential marker proteins both for monitoring the progression of the disease and
      as possible targets of pharmacological intervention. This is to my knowledge the
      first study of the proteome of the transformed lymphocytes in the course of
      bovine leukemia virus-induced leukemia in susceptible animals. BLV can be
      considered as useful model for related human pathogen - HTLV-1, another member of
      the deltaretrovirus genus evolutionary closely related to BLV. Information
      gathered in this study can be useful to speculate on possible shared mechanisms
      of deltaretrovirus-induced carcinogenesis.

PMID- 28436274
TI  - Featured Article: Depletion of HDL3 high density lipoprotein and altered
      functionality of HDL2 in blood from sickle cell patients.
AB  - In sickle cell disease (SCD), alterations of cholesterol metabolism is in part
      related to abnormal levels and activity of plasma proteins such as lecithin
      cholesterol acyltransferase (LCAT), and apolipoprotein A-I (ApoA-I). In addition,
      the size distribution of ApoA-I high density lipoproteins (HDL) differs from
      normal blood. The ratio of the amount of HDL2 particle relative to the smaller
      higher density pre-beta HDL (HDL3) particle was shifted toward HDL2. This
      lipoprotein imbalance is exacerbated during acute vaso-occlusive episodes (VOE)
      as the relative levels of HDL3 decrease. HDL3 deficiency in SCD plasma was found
      to relate to a slower ApoA-I exchange rate, which suggests an impaired ABCA1
      mediated cholesterol efflux in SCD. HDL2 isolated from SCD plasma displayed an
      antioxidant capacity normally associated with HDL3, providing evidence for a
      change in function of HDL2 in SCD as compared to HDL2 in normal plasma. Although
      SCD plasma is depleted in HDL3, this altered capacity of HDL2 could account for
      the lack of difference in pro-inflammatory HDL levels in SCD as compared to
      normal. Exposure of human umbilical vein endothelial cells to HDL2 isolated from
      SCD plasma resulted in higher mRNA levels of the acute phase protein long
      pentraxin 3 (PTX3) as compared to incubation with HDL2 from control plasma.
      Addition of the heme-scavenger hemopexin protein prevented increased expression
      of PTX3 in sickle HDL2-treated cells. These findings suggest that ApoA-I
      lipoprotein composition and functions are altered in SCD plasma, and that whole
      blood transfusion may be considered as a blood replacement therapy in SCD. Impact
      statement Our study adds to the growing evidence that the dysfunctional red blood
      cell (RBC) in sickle cell disease (SCD) affects the plasma environment, which
      contributes significantly in the vasculopathy that defines the disease.
      Remodeling of anti-inflammatory high density lipoprotein (HDL) to pro
      inflammatory entities can occur during the acute phase response. SCD plasma is
      depleted of the pre-beta particle (HDL3), which is essential for stimulation of
      reverse cholesterol from macrophages, and the function of the larger HDL2
      particle is altered. These dysfunctions are exacerbated during vaso-occlusive
      episodes. Interaction of lipoproteins with endothelium increases formation of
      inflammatory mediators, a process counteracted by the heme-scavenger hemopexin.
      This links hemolysis to lipoprotein-mediated inflammation in SCD, and hemopexin
      treatment could be considered. The use of RBC concentrates in transfusion therapy
      of SCD patients underestimates the importance of the dysfunctional plasma
      compartment, and transfusion of whole blood or plasma may be warranted.

PMID- 28436275
TI  - Total lumbar facetectomy without fusion: short and long term follow-up in a
      single surgeon series.
AB  - BACKGROUND: Total lumbar facetectomy may be advantageous for exposure or to
      completely free a constricted nerve root. OBJECTIVE: We retrospectively reviewed
      a single surgeon series without fusion for short and long term outcomes regarding
      radicular pain relief, subsequent relevant surgeries, and any identifiable
      instability. METHODS: All operations in which a single, total lumbar facetectomy
      was performed were reviewed. A total of 222 patients were identified with a
      minimal follow-up of 3 months; 187 (84.2%) were available for long term follow-up
      >=1 year by continued accessible health care records, correspondence, or mailed
      questionnaire. RESULTS: Short term success (3-month follow-up) for radicular pain
      relief in 222 patients found the following results: 176 patients (79.3%) had no
      pain or minimal pain, and 16 patients (7.2%) were improved, and thus resulting in
      192 (86.5%) with no pain, or improved radicular pain. 30 patients (13.5%) were
      postoperative failures at 3 months. Long term follow-up >=1 year was available
      for 187 patients (84.2%); (range 1-17 years; mean 7 years); found the following
      results: 23/30 (76.6%) short term surgical failures remained failures in long
      term follow-up with (7 patients) or without (16 patients) further surgery of any
      kind; 13/16 improved patients at long term follow-up remained improved (6), were
      pain free (6), or worse (1); 19/151 no or minimal pain patients at long term
      follow-up recurred or worsened by 1 year or longer, 12/19 pursued a second
      surgery with (9) or without (4) fusion and many improved. A total of 13 patients
      had a subsequent fusion operation (6.95%). DISCUSSION: Most patients do well in
      the short term for radicular pain relief. Most patients continue to do well in
      long term follow-up. Surgically induced clinical instability is uncommon in this
      highly selected series.

PMID- 28436276
TI  - Should trained lay providers perform HIV testing? A systematic review to inform
      World Health Organization guidelines.
AB  - New strategies for HIV testing services (HTS) are needed to achieve UN 90-90-90
      targets, including diagnosis of 90% of people living with HIV. Task-sharing HTS
      to trained lay providers may alleviate health worker shortages and better reach
      target groups. We conducted a systematic review of studies evaluating HTS by lay
      providers using rapid diagnostic tests (RDTs). Peer-reviewed articles were
      included if they compared HTS using RDTs performed by trained lay providers to
      HTS by health professionals, or to no intervention. We also reviewed data on end
      users' values and preferences around lay providers preforming HTS. Searching was
      conducted through 10 online databases, reviewing reference lists, and contacting
      experts. Screening and data abstraction were conducted in duplicate using
      systematic methods. Of 6113 unique citations identified, 5 studies were included
      in the effectiveness review and 6 in the values and preferences review. One US
      based randomized trial found patients' uptake of HTS doubled with lay providers
      (57% vs. 27%, percent difference: 30, 95% confidence interval: 27-32, p < 0.001).
      In Malawi, a pre/post study showed increases in HTS sites and tests after
      delegation to lay providers. Studies from Cambodia, Malawi, and South Africa
      comparing testing quality between lay providers and laboratory staff found little
      discordance and high sensitivity and specificity (>=98%). Values and preferences
      studies generally found support for lay providers conducting HTS, particularly in
      non-hypothetical scenarios. Based on evidence supporting using trained lay
      providers, a WHO expert panel recommended lay providers be allowed to conduct HTS
      using HIV RDTs. Uptake of this recommendation could expand HIV testing to more
      people globally.

PMID- 28436277
TI  - Single-pass endovascular thrombectomy for massive carotid-cerebral occlusion.
AB  - Acute concomitant occlusions of the extracranial internal carotid artery and
      intracranial vessels frequently require multiple passes with stent-retrievers for
      mechanical thrombectomy. Due to the large clot burden associated with these
      occlusions, their response to intravenous thrombolysis is poor. We herein report
      a successful case of evacuating a massive clot (>14 cm) in a single-pass using a
      stent-retrieval device.

PMID- 28436278
TI  - Glaucoma correlates with increased risk of Parkinson's disease in the elderly: a
      national-based cohort study in Taiwan.
AB  - BACKGROUND/OBJECTIVE: Very little is known about the association between glaucoma
      and Parkinson's disease in the elderly. The objective of this study was to
      determine whether glaucoma is associated with Parkinson's disease in older people
      in Taiwan. METHODS: A retrospective cohort study was conducted to analyze the
      Taiwan National Health Insurance Program database from 2000 to 2010. We included
      4330 subjects aged 65 years or older with newly diagnosed glaucoma as the
      glaucoma group, and 17,000 randomly selected subjects without a glaucoma
      diagnosis as the non-glaucoma group. Both groups were matched for sex, age, other
      comorbidities, and index year of glaucoma diagnosis. The incidence of Parkinson's
      disease at the end of 2011 was measured. A multivariable Cox proportional hazard
      regression model was used to measure the hazard ratio and 95% confidence
      intervals for Parkinson's disease associated with glaucoma. RESULTS: The overall
      incidence of Parkinson's disease was 1.28-fold higher in the glaucoma group than
      that in the non-glaucoma group (7.73 vs. 6.02 per 1000 person-years; 95%
      confidence interval 1.18, 1.40). After controlling for potential confounding
      factors, the adjusted hazard ratio of Parkinson's disease was 1.23 for the
      glaucoma group (95% confidence interval 1.05, 1.46), compared with the non
      glaucoma group. CONCLUSIONS: Older people with glaucoma correlate with a small
      but statistically significant increase in the risk for Parkinson's disease.
      Whether glaucoma may be a non-motor feature of Parkinson's disease in older
      people requires further research to confirm.

PMID- 28436279
TI  - Treatment of painful radiculopathies with capsaicin 8% cutaneous patch.
AB  - BACKGROUND AND OBJECTIVE: The treatment of neuropathic pain due to low-back
      (lumbosacral) radiculopathies, a common source of neuropathic pain, is
      challenging and often requires a multimodal therapeutic approach. The capsaicin
      8% patch is the first topical analgesic licensed for peripheral neuropathic pain.
      To evaluate this treatment, a subset of patients with painful radiculopathy
      (lumbar and cervical, including ventral and dorsal rami) enrolled into the
      multicenter, non-interventional QUEPP study (Qutenza 2 - safety and effectiveness
      in peripheral neuropathic pain) was analyzed. METHODS: Of the 1044 study
      participants, 50 were diagnosed with painful radiculopathy as only peripheral
      neuropathic pain syndrome and were eligible for evaluation. Patients received a
      single treatment (visit 1) with follow-up visits 2-5 at weeks 1-2, 4, 8 and 12.
      Parameters assessed at all visits included pain intensity, neuropathy symptoms
      and side effects. Quality of life (SF-12) and painDETECT 1 questionnaires were
      completed at baseline and final visit. Data was analyzed by patch application
      site and duration of pain. RESULTS: Topical treatment led to a significant
      decrease of pain intensity between weeks 1/2 and week 12 versus baseline at the
      application sites representing dermatomes of ventral (N = 26) and dorsal rami (N
      = 13) of spinal nerves. A significant decline (p <= .001) of numeric pain rating
      scale scores was observed between weeks 1/2 following patch application and the
      end of observation (week 12) in the overall radiculopathy group (N = 50), and the
      groups with either 3 months to 2 years (N = 14) or >2 years (N = 23) duration of
      pain. Pain relief of at least 30% was observed in 50.0%, 71.4% and 39.1% of
      patients in the respective groups. Four patients experienced in total seven
      adverse drug reactions (application site pain or pruritus). CONCLUSION: Effective
      neuropathic pain relief was observed after patch application within the
      innervation territories of both dorsal and ventral branches of the spinal nerve.
      Further controlled randomized trials are indicated.

PMID- 28436280
TI  - Persistent foot ulcer due to ruxolitinib therapy for primary myelofibrosis.
AB  - Primary myelofibrosis is characterized by bone marrow fibrosis, splenomegaly and
      presence of JAK-2 V617F mutation in more than 90% of patients. Ruxolitinib is a
      Janus kinase inhibitor used for the treatment of primary myelofibrosis. We
      describe herein a persistent foot ulcer development attributed to ruxolitinib
      therapy. We are unaware of any previous reports of this phenomenon in the
      scientific literature. A thorough examination of the lower extremities is perhaps
      necessary before initiating this oral agent. If ruxolitinib therapy cannot be
      safely discontinued, diligent wound care and a course of antibiotics are
      warranted.

PMID- 28436281
TI  - Terfenadine t-butyl hydroxylation catalyzed by human and marmoset cytochrome P450
      3A and 4F enzymes in livers and small intestines.
AB  - 1. Roles of human cytochrome P450 (P450) 3A4 in oxidation of an antihistaminic
      drug terfenadine have been previously investigated in association with
      terfenadine-ketoconazole interaction. Several antihistamine drugs have been
      recently identified as substrates for multiple P450 enzymes. In this study,
      overall roles of P450 3A4, 2J2, and 4F12 enzymes in terfenadine t-butyl
      hydroxylation were investigated in small intestines and livers from humans,
      marmosets, and/or cynomolgus monkeys. 2. Human liver microsomes and liver and
      small intestine microsomes from marmosets and cynomolgus monkeys effectively
      mediated terfenadine t-butyl hydroxylation. Ketoconazole and N-hydroxy-N'-(4
      butyl-2-methylphenyl)-formamidine (a P450 4A/F inhibitor) almost completely and
      moderately inhibited these activities, respectively, in human liver microsomes;
      however, these chemicals did not show substantially suppression in marmoset
      liver. Anti-human P450 3A and 4F antibodies showed the roughly supportive
      inhibitory effects. 3. Recombinant P450 3A4/90 and 4F12 showed high terfenadine t
      butyl hydroxylation activities with substrate inhibition constants of 84-144 MUM
      (under 26-76 MUM of Km values), in similar manners to liver and intestine
      microsomes. 4. These results suggest that human and marmoset P450 3A4/90 and 4F12
      in livers or small intestines played important roles in terfenadine t-butyl
      hydroxylation. Marmosets could be a model for humans during first pass extraction
      of terfenadine and related substrates.

PMID- 28436282
TI  - The effect of chamomile extract obtained in supercritical carbon dioxide
      conditions on physicochemical and usable properties of pharmaceutical ointments.
AB  - The study investigated the effect of chamomile extract obtained in supercritical
      carbon dioxide conditions on the basic properties of pharmaceutical ointments. A
      total of five formulations were designed and prepared, differing in the weight
      ratio of sunflower oil to chamomile extract (5:0, 3.5:1.5, 2.5:2.5, 1.5:3.5 and
      0:5). An increase in the concentration of chamomile extract was found to be
      accompanied by a decrease in hardness, adhesive power and flow limit. Based on
      viscosity measurements it was shown that ointments containing the hydrophobic
      plant extract under study were prone to larger drops in viscosity under the
      effect of the set shear rate. It was determined that from the viewpoint of
      ointment spreadability and application to the skin, the optimum concentration of
      chamomile extract for the studied formulations should be within the range of 1.5
      2.5%. Furthermore, the addition of chamomile extract to ointments was found to
      give samples a yellow-green color. Green was observed to be the dominant color,
      and its saturation and shade varied for different formulations.

PMID- 28436283
TI  - Trigger Factors in Childhood Migraine: A Prospective Clinic-Based Study From
      North of France.
AB  - The objective was to study the prevalence and characterization of pediatric
      migraine triggers and to compare results to this retrospective study. A total of
      101 pediatric patients with ICHD-II migraine with and/or without aura were
      instructed to prospectively complete a diary dealing with attacks triggers for a
      3-month period. Each subject reported at least 1 trigger (range: 1-14) with a
      total number of 532 attacks and a median per subject of 3. Lack of sleep (51.4%),
      stress (44.6%), warm climate (41.9%), noise (32.4%), and excitation (29.7%) were
      the most frequently reported. The delay between trigger exposure and attack onset
      was between 0 and 3 hours in 67.6% of attacks. This prospective study confirmed
      the findings of the authors' previous study, with the exception that number of
      triggers was smaller, probably due to recall bias. The 4 most frequent triggers
      (lack of sleep, stress, hot weather, and noise) were identical in both studies.

PMID- 28436284
TI  - Exertional Heat Illness Among Secondary School Athletes: Statewide Policy
      Implications.
AB  - Exertional heat illness (EHI) is a leading cause of preventable death among
      student athletes. While causes and preventative measures for EHI are known,
      school districts may not be implementing evidence-based practices. This
      descriptive, exploratory study explored school policies, resources, and practices
      of coaches in a mid-Atlantic state in the prevention and identification of EHI;
      397 responded. Ninety-three percent knew of EHI, but only 52% scheduled
      acclimatization. Coaches reporting a heat emergency plan (56%) were significantly
      more likely to follow other evidence-based recommendations: altering equipment (
      p < .0001, odds ratio [ OR] = 2.53), monitoring environment ( p < .0001, OR =
      2.56), providing acclimatization ( p < .0001, OR = 2.50), having athletic
      trainers at practices ( p < .0001, OR = 4.75), and believed that they could
      handle the emergency until EMS arrival ( p < .001, OR = 2.48). School districts
      should comply with evidence-based guidelines. School nurses play a key role in
      education, developing emergency plans and training coaches in first aid.

PMID- 28436285
TI  - Musculoskeletal Injuries Associated With Hoverboard Use in Children.
AB  - Hoverboards burst onto the scene with wide popularity only to be quickly deemed
      unsafe and banned in many arenas. We conducted a retrospective cohort study of 35
      patients seen in our outpatient pediatric orthopedic office over a 1-year period.
      The mean age of injured patients was 11.14 years; 18 patients were male (51.4%),
      and 17 were female (48.5%). The highest number of injuries occurred in children
      10 to 14 years old who had 57.1% of the injuries. There were a total of 31
      fractures in 27 patients. Most of the fractures were in the upper extremities
      (93.6 %). Also, 9 soft-tissue injuries were found in 8 patients; 88.9 % of
      injuries occurred in the upper extremities. Most of the injuries were secondary
      to a fall (94.3%). We found that the most common injury was upper-extremity
      fracture. We suggest restricting riding <16 years and encourage protective
      equipment, especially elbow and wrist guards.

PMID- 28436287
TI  - Positive affect and physical activity: Testing effects on goal setting,
      activation, prioritisation, and attainment.
AB  - OBJECTIVE: The present research tested whether incidental positive affect
      promotes pursuit of physical activity goals. Four key features of goal pursuit
      were examined - setting physical activity goals (Study 1), goal activation (Study
      2), and goal prioritization and goal attainment (Study 3). DESIGN: Participants
      (Ns = 80, 81, and 59, in Studies 1-3, respectively) were randomized to positive
      affect (joy, hope) or neutral affect (control) conditions in each study. MAIN
      OUTCOME MEASURES: Questionnaire measures of goal level, goal commitment, and
      means selection (Study 1); a lexical decision task indexed goal activation (Study
      2), a choice task captured goal prioritization and MET minutes quantified goal
      attainment (Study 3). RESULTS: Study 1 showed that positive affect led to a
      greater number of intended physical activities, and that joy engendered greater
      willingness to try activities. In Study 2, a positive affect induction led to
      heightened activation of the physical activity goal compared to the control
      condition. The joy induction in Study 3 led to greater physical activity, and a
      trend towards greater goal prioritization. CONCLUSION: These findings suggest
      that positive affect enhances the pursuit of physical activity goals.
      Implications for health behavior theories and interventions are outlined.

PMID- 28436286
TI  - Coordinated Asthma Program Improves Asthma Outcomes in High-Risk Children.
AB  - Innovative approaches within primary care are needed to reduce fragmented care,
      increase continuity of care, and improve asthma outcomes in children with asthma.
      Our objective was to assess the impact of coordinated team-based asthma care on
      unplanned asthma-related health care utilization. A multidisciplinary asthma team
      was developed to provide coordinated care to high-risk asthma patients. Patients
      received an in-depth diagnostic and family needs assessment, asthma education,
      and coordinated referral to social and community services. Over a 2-year period,
      141 patients were followed. At both 1 and 2 years postintervention, there was a
      significant decrease from preintervention rates in urgent care visits (40%, P =
      .002; 50%, P < .0001), emergency department visits (63%, P < .0001; 70%, P <
      .0001), and inpatient hospitalization (69%, P = .002; 54%, P = .04). Our
      coordinated asthma care program was associated with a reduction in urgent care
      visits, emergency department visits, and inpatient hospitalizations among high
      risk children with asthma.

PMID- 28436288
TI  - Ossifying Fibromyxoid Tumor of the Retromolar Trigone: A Case Report and
      Systematic Review of the Literature.
AB  - Ossifying fibromyxoid tumor (OFMT) is a mesenchymal neoplasm of uncertain lineage
      and intermediate biologic behavior. Involvement of the head and neck area is
      infrequent (10% to 15%) and intraoral presentation is very rare. An OFMT
      developing in the retromolar trigone of a 13-year-old male is presented, along
      with a comprehensive review of oral OFMT cases. Among 12 oral OFMTs (including
      the present case), most patients were male (72.7%), with a mean age of 30.3 (13
      67) years. The tumors generally appeared as painless masses of firm or hard
      consistency (mean diameter 27.7 mm), most commonly located in the soft tissues of
      the mandible (50%). Common microscopic features included ossification, lack of
      atypia or high mitotic activity, and immunohistochemical positivity for S100
      (5/7), vimentin (6/6), GFAP (3/6), and SMA (2/6). Recurrence was reported only in
      one case. Further characterization of this rare entity is needed to increase our
      understanding of its distinct clinical and histopathologic features.

PMID- 28436289
TI  - Comparison of Renal Anastomosing Hemangiomas in End-Stage and Non-End-Stage
      Kidneys: A Meta-Analysis With a Report of 2 Cases.
AB  - BACKGROUND: Renal anastomosing hemangioma (RAH) is a very rare distinct entity
      composed of anastomosing sinusoidal (spleen-like) capillary-sized vessels lined
      by flat or hobnail endothelial cells. Most of the published cases of RAH occurred
      in the setting of end-stage renal disease (ESRD). METHODS: We present 2 cases of
      RAH in ESRD along with a literature review. We compared clinicopathologic
      features of RAHs in end-stage and non-end-stage kidneys. A meta-analysis was
      conducted with PubMed and a manual search through references of relevant
      publications. Individual patient data gathered from the literature were used in
      the analysis. RESULTS: Our systematic review revealed 49 RAHs, including our 2
      cases. Thirty-two (65.3%) cases were in ESRD, only 17 (34.7%) were in patients
      with non-ESRD. RAHs in ESRD were in younger patients, smaller in size,
      multifocal, and seen more with renal epithelial neoplasms when compared with RAHs
      in non-ESRD ( P < .05). Extramedullary hematopoiesis was seen mostly in RAHs in
      ESRD kidneys (85% vs 41.7%) ( P = .018). Follow-up data were available for 25
      cases with a mean follow-up of 24.58 +/- 38.54 months. Recurrence, metastasis, or
      death have never been described related to RAH in any patients. CONCLUSIONS: In
      conclusion, RAHs are rare and mostly arise in kidneys with end-stage damage. RAHs
      in ESRD and non-ESRD differ in terms of clinicopathologic features.

PMID- 28436290
TI  - Topography of Protein Kinase C betaII in Benign and Malignant Melanocytic
      Lesions.
AB  - BACKGROUND: Protein kinase C betaII promotes melanogenesis and affects
      proliferation of melanocytic cells but is frequently absent or decreased in
      melanoma cells in vitro. OBJECTIVE: To investigate PKC-betaII expression and
      spatial distribution within a lesion in various benign and malignant melanocytic
      proliferations. METHODS: Expression of PKC-betaII was semiquantitatively assessed
      in the various existing compartments (intraepidermal [not nested], junctional
      [nested], and dermal) of benign (n = 43) and malignant (n = 28) melanocytic
      lesions by immunohistochemistry. RESULTS: Melanocytes in the basal layer of
      normal skin or in lentigo simplex stained strongly for PKC-betaII. Common nevi
      lacked completely PKC-betaII. All other lesions expressed variably PKC-betaII,
      with cutaneous melanoma metastases displaying the lowest rate of positivity
      (14%). In the topographical analysis within a lesion, PKC-betaII expression was
      largely retained in the intraepidermal and junctional part of all other lesions
      (dysplastic nevus, lentigo maligna, and melanoma). Reduced expression of PKC
      betaII was found in the dermal component of benign and malignant lesions ( P =
      .041 vs intraepidermal). PKC-betaII expression in the various compartments did
      not differ significantly between benign and malignant lesions. CONCLUSIONS: The
      current study revealed a significant correlation between PKC-betaII expression
      and spatial localization of melanocytes, with the lowest expression found in the
      dermal compartment and the highest in the epidermal compartment.

PMID- 28436291
TI  - A simulator for nerve repair.

PMID- 28436293
TI  - Food Insecurity and Depression Among Adults With Diabetes: Results From the
      National Health and Nutrition Examination Survey (NHANES).
AB  - Purpose While both food insecurity and depression have been linked to risk of
      type 2 diabetes, little is known about the relationship between food insecurity
      and depression among adults with diabetes. Research Design and Methods Cross
      sectional analyses of the National Health and Nutrition Examination Survey (2011
      2014), a nationally representative, population-based survey. Analytic sample was
      limited to adults aged >=20 with diabetes determined by either fasting plasma
      glucose (>=126 mg/dL) or self-report (n = 1724) and adults age >=20 with
      prediabetes determined by fasting plasma glucose (100-125 mg/dL) or self-report
      (n = 2004). Food insecurity was measured using the US Food Security Survey
      Module. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9).
      Logistic regression was used to assess the relationship between food insecurity
      and depression while accounting for sociodemographic characteristics and health
      behaviors. Results Approximately 10% of individuals with diabetes and 8.5% of
      individuals with prediabetes had severe food insecurity in the past year; an
      additional 20.3% of individuals with diabetes and 14.3% of those with prediabetes
      had mild food insecurity. Among individuals with diabetes, both mild and severe
      food insecurity were associated with elevated odds of depression These
      relationships were similar in magnitude among individuals with prediabetes.
      Conclusions Food insecurity is significantly associated with depressive symptoms
      in people with diabetes and prediabetes. Results point to the need to address
      economic issues in conjunction with psychosocial issues for comprehensive
      diabetes care.

PMID- 28436295
TI  - Treatment response to dimethyl fumarate is characterized by disproportionate CD8+
      T cell reduction in MS.
AB  - BACKGROUND: The effect of dimethyl fumarate (DMF) on circulating lymphocyte
      subsets and their contribution as predictors of clinical efficacy have not yet
      been investigated in multiple sclerosis (MS). OBJECTIVE: To evaluate lymphocytes
      and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with
      and without disease activity after 1 year of treatment in a retrospective study.
      METHODS: Peripheral blood lymphocyte subsets were analyzed by flow cytometry.
      Untreated MS patients ( n = 40) were compared to those 6 months after onset of
      DMF treatment ( n = 51). Clinical and magnetic resonance imaging (MRI) disease
      activity of DMF-treated patients were assessed in the first year under treatment.
      RESULTS: Stable patients showed significantly lower lymphocytes, CD4+ and CD8+ T
      cells as well as CD19+ B cells compared to active patients under DMF treatment.
      Furthermore, an increased CD4/CD8 ratio ( p < 0.025) in stable patients indicated
      a disproportionate reduction of CD8+ T cells relative to CD4+ T cells. Reduced
      lymphocytes, CD8+ T cells, and CD19+ B cells 6 months after DMF start allowed
      prediction of the treatment response in the first year. CONCLUSION: DMF treatment
      response is reflected by lower circulating lymphocytes and specific lymphocyte
      subsets. Changes in the cellular immune profiles under DMF treatment are
      clinically relevant and might serve as a surrogate marker of treatment response.

PMID- 28436294
TI  - Overexpression of VLA-4 in glial-restricted precursors enhances their endothelial
      docking and induces diapedesis in a mouse stroke model.
AB  - The loss of oligodendrocytes after stroke is one of the major causes of secondary
      injury. Glial-restricted progenitors (GRPs) have remylenating potential after
      intraparenchymal cerebral transplantation. The intraarterial (IA) injection route
      is an attractive gateway for global brain delivery, but, after IA infusion, naive
      GRPs fail to bind to the cerebral vasculature. The aim of this study was to test
      whether overexpression of Very Late Antigen-4 (VLA-4) increases endothelial
      docking and cerebral homing of GRPs in a stroke model. Mouse GRPs were co
      transfected with DNA plasmids encoding VLA-4 subunits (alpha4, beta1). The
      adhesion capacity and migration were assessed using a microfluidic assay. In vivo
      imaging of the docking and homing of IA-infused cells was performed using two
      photon microscopy in a mouse middle cerebral artery occlusion (MCAO) model.
      Compared to naive GRPs, transfection of GRPs with VLA-4 resulted in >60% higher
      adhesion (p < 0.05) to both purified Vascular Cell Adhesion Molecule-11 (VCAM-11)
      and TNFalpha-induced endothelial VCAM-1. VLA-4+GRPs displayed a higher migration
      in response to a chemoattractant gradient. Following IA infusion, VLA-4+GRPs
      adhered to the vasculature at three-fold greater numbers than naive GRPs. Multi
      photon imaging confirmed that VLA-4 overexpression increases the efficiency of
      GRP docking and leads to diapedesis after IA transplantation. This strategy may
      be further exploited to increase the efficacy of cellular therapeutics.

PMID- 28436296
TI  - Synthesis, characterization, DNA and HSA binding studies of isomeric Pd (II)
      antitumor complexes using spectrophotometry techniques.
AB  - Two new Palladium(II) isomeric complexes, [Pd (Gly)(Leu)](I) and [Pd
      (Gly)(Ile)](II), where Gly is glycine, and Leu and Ile are isomeric amino acids
      (leucine and isoleucine), have been synthesized and characterized by elemental
      analysis, molar conductivity measurements, FT-IR, 1H NMR, and UV-Vis. The
      complexes have been tested for their In vitro cytotoxicity against cancer cell
      line K562 and their binding properties to calf thymus DNA (CT-DNA) and human
      serum albumin (HSA) have also been investigated by multispectroscopic techniques.
      Interactions of these complexes with CT-DNA were monitored using gel
      electrophoresis. The energy transfer from HSA to these complexes and the binding
      distance between HSA and the complexes (r) were calculated. The results obtained
      from these studies indicated that at very low concentrations, both complexes
      effectively interact with CT-DNA and HSA. Fluorescence studies revealed that the
      complexes strongly quench DNA bound ethidium bromide as well as the intrinsic
      fluorescence of HSA through the static quenching procedures. Binding constant
      (Kb), apparent biomolecular quenching constant (kq), and number of binding sites
      (n) for CT-DNA and HSA were calculated using Stern-Volmer equation. The
      calculated thermodynamic parameters indicated that the hydrogen binding and
      vander Waals forces might play a major role in the interaction of these complexes
      with HSA and DNA. Thus, we propose that the complexes exhibit the groove binding
      with CT-DNA and interact with the main binding pocket of HSA. The complexes
      follow the binding affinity order of I > II with DNA- and II > I with HSA
      binding.

PMID- 28436297
TI  - Health impact assessment (HIA) of political proposals at the local level:
      successful introduction, but what has happened 15 years later?
AB  - Health impact assessments (HIAs) were first introduced in Sweden in the mid-to
      late 1990s, with the aim of placing health issues on the political agenda and
      helping to reduce health inequalities. In the early 2000s, HIAs entered a second
      phase and the Swedish Parliament adopted a national public health policy. A
      national survey conducted in 2001 showed that 10/289 municipalities had begun to
      use HIA and 55/289 had decided to use HIA or had initiated an adoption process.
      In a 2013 follow-up study based on a strategic sample of municipalities, 9/36
      municipalities reported using HIA and/or similar tools. Corresponding figures for
      the 21 Swedish regions were 10 regions in 2001 and four in 2013. HIA and similar
      tools (sustainability analyses, child impact assessments, and others) were
      applied to the same extent as HIA. Fifteen years after implementation began, HIA
      is still being used. Regions show a clear decrease in the use of HIA. There are
      several explanations for this development. One is the political context, and
      other explanations are shifts in which actors are responsible for HIA and for
      public health at the local/regional levels.

PMID- 28436298
TI  - Adenocarcinoma of the appendix occurring in a patient treated with paclitaxel for
      locally advanced esophageal cancer.
AB  - Paclitaxel has been linked with a number of immunosuppressive effects such as
      decreased numbers and activity of dendritic cells, NK-cells and monocytes, which
      may in turn lead to defective T-cell activation. In addition, this agent was
      shown to cause mitotic arrest resembling high-grade dysplasia throughout the
      gastrointestinal tract, including the appendix. We have previously documented a
      series of lung cancer patients who developed pre-malignant colonic polyps and/or
      colon cancer either during or weeks following chemotherapy with paclitaxel,
      suggesting a potential role of this agent in their pathogenesis. We describe
      herein a patient who developed adenocarcinoma of the appendix five months after
      paclitaxel therapy for a locally advanced lower esophageal cancer. Although the
      cancer of the appendix was in early stage, it was poorly differentiated and
      showed lymphovascular invasion. The context, timeline and existing experience
      suggest that this second cancer was triggered by a pre-existing insult,
      conceivably delivered by paclitaxel.

PMID- 28436299
TI  - MGMT gene variants, temozolomide myelotoxicity and glioma risk. A concise
      literature survey including an illustrative case.
AB  - Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma
      patients, respectively. However, pancytopenia is rarely reported. MGMT (O6
      methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA
      mutations and associates both with antitumour efficacy and myelosuppression. Many
      studies on the effects of MGMT gene-methylation on temozolomide's effects exist,
      but much fewer publications concerning MGMT variants were documented. A full
      sequencing of the MGMT gene was performed in a female glioblastoma patient, who
      developed pancytopenia following temozolomide treatment. Results indicated the
      presence of all the rs2308321 (I143 V), rs2308327 (K178R) and rs12917 (L84F) MGMT
      variants, which were previously associated with temozolomide myelotoxicity.
      rs12917 (L84F) variant was reported as associating with lesser risk of
      gallbladder tumours, yet with higher risk of non-Hodgkin lymphomas related with
      exposure to chlorinated solvents or hair dyes. DNA repair proteins may exert
      diverging effects on DNA injuries caused by different chemicals and therefore
      exerting complex effects on myelotoxicity, antitumour activity and
      carcinogenesis.

PMID- 28436300
TI  - Ten-year single-centre experience with type II endoleaks: Intervention versus
      observation.
AB  - Our objective was to determine the relative merits of intervention or observation
      of type II endoleaks (T2Ls). A retrospective analysis was performed on 386 infra
      renal endovascular aneurysm repair (IR-EVAR) patients from 2006 to 2015. Annual
      surveillance imaging of patients undergoing EVAR at our centre were analysed, and
      all endoleaks were subjected to a multidisciplinary team meeting for
      consideration and treatment. In the 10-year time frame, 386 patients (79.5+/-8.7
      years) underwent an IR-EVAR. Eighty-one patients (21.0%) developed a T2L and
      intervention was undertaken in 28 (34.6%): 17 (60.7%) were treated via a
      transarterial approach (TA) and 11 (39.3%) using the translumbar approach (TL).
      Fifty-three patients (65.4%) with T2Ls were managed conservatively. Patients who
      received T2L treatment had a greater proportion of recurrent T2Ls than patients
      who were conservatively managed ( p=0.032). T2Ls associated with aneurysmal
      growth were more resistant to treatment than those where there was no change or a
      decrease in aneurysm size during follow-up (0.033). There was no significant
      difference in the TA and TL approach with respect to endoleak repair success (
      p=0.525). Treatment of a T2L did not confer a survival advantage compared to
      conservative management ( p=0.449) nor did the choice of either the TA or TL
      approach ( p=0.148). Our study suggests the development of a T2L associated with
      aneurysm growth may represent an aggressive phenotype that is resistant to
      treatment. However, this did not lead to an increased risk of mortality over
      follow-up. Neither a transarterial nor a translumbar approach to treating a T2L
      conferred superiority.

PMID- 28436301
TI  - Orthodontic treatment modalities: a qualitative assessment of Internet
      information.
AB  - OBJECTIVES: The present study aimed to determine the quality, accuracy,
      reliability and usability of Internet information, regarding different
      orthodontic treatment modalities. METHOD: Google AdWords identified five popular
      keywords: Cosmetic braces, fixed braces, Removable braces, Quick braces and
      risks. These were entered in five search engines, with the resultant websites
      analysed using five validated assessment tools. Intra-examiner reliability was
      assessed, descriptive and inferential analysis of the data undertaken. RESULTS:
      Good intra-examiner reliability and consistency was observed. A total of 119
      websites were included for analysis, with the keywords cosmetic and fixed braces
      accounting for 55% of identified websites. Invisalign was the most offered
      treatment (80%). Specialist orthodontists produced the highest, whilst general
      dentists advertising short-term options produced the lowest quality scoring
      websites. LIDA provided the most accurate assessment of quality (mean 62.02, SD
      7.48). Regression analysis found a significant relationship between author type
      and a questions and answer sections with both Discern (P < 0.001) and LIDA (P =
      0.002) scores, respectively. CONCLUSIONS: Quality of Information regarding
      orthodontic treatment was variable, with the highest scoring websites were
      produced by orthodontic specialists and Invisalign the most offered treatment.
      There is a clear need for valid and reliable websites to better guide patients.

PMID- 28436302
TI  - Gene set enrichment analysis: A genome-wide expression profile-based strategy for
      discovering functional microRNA-disease relationships.
AB  - Objective To explore stable and functional microRNA (miRNA)-disease relationships
      using a genome-wide expression profile pattern matching strategy. Methods We
      applied the ranked microarray pattern matching strategy Gene Set Enrichment
      Analysis to identify miRNA permutations with similar expression patterns to
      diseases. We also used quantitative reverse transcription PCR to validate the
      predicted expression levels of miRNAs in three diseases: inflammatory bowel
      disease (IBD), oesophageal cancer, and colorectal cancer. Results We found that
      hsa-miR-200 c was upregulated more than 40-fold in oesophageal cancer. The
      expression of miR-16 and miR-124 was not consistently upregulated in IBD or
      colorectal cancer. Conclusions Our results suggest that this expression profile
      matching strategy can be used to identify functional miRNA-disease relationships.

PMID- 28436303
TI  - Choline Supplementation During Pregnancy Protects Against Gestational
      Lipopolysaccharide-Induced Inflammatory Responses.
AB  - OBJECTIVES: To estimate the effects and mechanisms of choline, an essential
      nutrient and a selective alpha7 nicotinic acetylcholine receptor (alpha7nAChR)
      agonist, on the prevention of symptoms and the effects on the cholinergic anti
      inflammatory pathways (CAP) in a lipopolysaccharide (LPS)-induced inflammatory
      response in a rat model. METHODS: Inflammation was induced by LPS treatment (1.0
      MUg LPS/kg body weight) on gestational day (GD) 14. Nonpregnant and pregnant
      Sprague Dawley rats were placed on a normal choline diet (1.1 g/kg) or
      supplemented choline diet (5.0 g/kg) from GDs 1 to 20. Systolic blood pressure
      (SBP), urinary albumin, and pregnancy outcomes were recorded. On GD 20, serum and
      placentas were assayed for cytokines. Western blots were used to determine the
      expression of placenta alpha7nAChR and components of the alpha7nAChR-CAP,
      including nuclear factor-kappaB (NF-kappaB) and protein kinase B (AKT).
      Immunohistochemistry was used to localize placental sites for the p65 subunit of
      NF-kappaB. RESULTS: Lipopolysaccharide significantly increased SBP and urinary
      albumin and decreased pregnancy outcomes, and these effects were partially
      reversed by higher choline treatment. Choline supplementation also significantly
      attenuated the LPS-induced increase in serum and placental inflammatory
      cytokines, decreased the expression of placental alpha7nAChR, lowered the
      activation of NF-kappaB signaling in placenta mononuclear cells, and inhibited
      placental AKT phosphorylation. CONCLUSION: This study confirms that LPS induces
      inflammatory conditions in pregnant rats and shows that choline supplementation
      protects against the inflammatory symptoms through its action on alpha7nAChR and
      CAP. These observations have important implications for the prevention and
      treatment of inflammatory responses associated with pregnancy.

PMID- 28436304
TI  - The PTEN inhibitor bpV(pic) promotes neuroprotection against amyloid beta-peptide
      (25-35)-induced oxidative stress and neurotoxicity.
AB  - OBJECTIVES: The aim of this study was to elucidate the mechanism underlying the
      neuroprotective effects of the phosphatase and tensin homolog (PTEN) inhibitor,
      bisperoxovanadium-pic [bpV(pic)]. METHODS: We determined the effects of bpV(pic)
      on amyloid-beta-peptide-(25-35)-induced neurotoxicity, particularly intracellular
      reactive oxygen species (ROS) production and mitochondria-mediated apoptotic
      signaling, in a human neuroblastoma (SH-SY5Y) cell model. RESULTS: We found that
      exposure of SH-SY5Y cells to amyloid beta peptides (Abeta25-35) resulted in a
      significant reduction in cell viability accompanied by increased lactate
      dehydrogenase (LDH) release, elevated levels of intracellular ROS, and decreased
      superoxide dismutase (SOD) activities, all of which were reversed by co-treatment
      with bpV(pic). Moreover, bpV(pic) induced significant protection against Abeta25
      35-induced apoptosis, and effectively suppressed mitochondria-dependent apoptotic
      signaling triggered by Abeta25-35. DISCUSSION: Abeta peptides are thought to
      cause neurodegeneration in Alzheimer's disease (AD), via the induction of free
      radical oxidative stress. Our results indicate that bpV(pic) provides protection
      against Abeta25-35-induced oxidative stress and neurotoxicity, suggesting that
      bpV(pic) could be a potential therapeutic candidate in the treatment of
      neurodegenerative diseases such as AD.

PMID- 28436305
TI  - Quality of life after intra-arterial treatment for acute ischemic stroke in the
      MR CLEAN trial-Update.
AB  - Background Health-related quality of life measured with the EuroQol Group 5
      Dimension Self-Report Questionnaire was one of the secondary outcomes in the
      Multicenter Randomized Clinical trial of Endovascular treatment for Acute
      ischemic stroke in the Netherlands (MR CLEAN). We reported no statistically
      significant difference in EuroQol Group 5-Dimension Self-Report Questionnaire
      score between the intervention and control groups, but deaths were not included.
      Aims Reanalyze the effect of intra-arterial treatment for large vessel occlusion
      in acute ischemic stroke patients on health-related quality of life in more
      detail. We now include patients who died during follow-up. Methods The EuroQol
      Group 5-Dimension Self-Report Questionnaire questionnaires were obtained 90 days
      after treatment. We used the Dutch tariff to derive a utility index from the
      EuroQol Group 5-Dimension Self-Report Questionnaire score. Treatment effect was
      estimated with the Mann-Whitney U test and linear regression. The effect of
      treatment on the distribution of EuroQol Group 5-Dimension Self-Report
      Questionnaire dimension scores was assessed with ordinal logistic regression.
      Results We obtained EuroQol Group 5-Dimension Self-Report Questionnaire scores
      from 457 (91.7%) of the 500 patients, including 108 who died before follow-up.
      Median EuroQol Group 5-Dimension Self-Report Questionnaire score in the
      intervention group was 0.57, and 0.39 in the control group (p = 0.03). Treatment
      effect estimated with linear regression was 0.07 (95%CI: -0.001 to 0.143).
      Treatment specifically affected EuroQol Group 5-Dimension Self-Report
      Questionnaire dimensions "mobility" (OR: 0.43, 95%CI: 0.29-0.66), "self-care"
      (OR: 0.60, 95%CI: 0.41-0.89), and "usual activities" (OR: 0.53, 95%CI: 0.36
      0.79). Conclusion Treatment had a limited effect on quality of life, as measured
      with the EuroQol Group 5-Dimension Self-Report Questionnaire. Nevertheless,
      patients with acute ischemic stroke caused by an intracranial occlusion in the
      anterior circulation, who had intra-arterial treatment, experience better health
      related quality of life than patients without intra-arterial treatment. Trial
      Registration URL: http://www.isrctn.com/ISRCTN10888758 Unique identifier:
      ISRCTN10888758.

PMID- 28436306
TI  - Cardiac magnetic resonance imaging has limited additional yield in cryptogenic
      stroke evaluation after transesophageal echocardiography.
AB  - Background The use of cardiac magnetic resonance imaging is increasing, but its
      role in the diagnostic work-up following ischemic stroke has received limited
      study. We aimed to explore the added yield of cardiac magnetic resonance imaging
      to identify cardio-aortic sources not detected by transesophageal
      echocardiography among patients with cryptogenic stroke. Methods A retrospective
      single-center cohort study was performed from 01 January 2009 to 01 March 2013.
      Consecutive patients who had both a stroke protocol cardiac magnetic resonance
      imaging and a transesophageal echocardiography preformed during a single
      hospitalization were included. All cardiac magnetic resonance imaging studies
      underwent independent, blinded review by two investigators. We applied the
      causative classification system for ischemic stroke to all patients, first
      blinded to cardiac magnetic resonance imaging results; we then reapplied the
      causative classification system using cardiac magnetic resonance imaging.
      Standard statistical tests to evaluate stroke subtype reclassification rates were
      used. Results Ninety-three patients were included in the final analysis; 68.8%
      were classified as cryptogenic stroke after initial diagnostic evaluation. Among
      patients with cryptogenic stroke, five (7.8%) were reclassified due to cardiac
      magnetic resonance imaging findings: one was reclassified as "cardio-aortic
      embolism evident" due to the presence of a patent foramen ovale and focal cardiac
      infarct and four were reclassified as "cardio-aortic embolism possible" due to
      mitral valve thickening (n = 1) or hypertensive cardiomyopathy (n = 3). Overall,
      findings on cardiac magnetic resonance imaging reduced the percentage of patients
      with cryptogenic stroke by slightly more than 1%. Conclusion Our stroke subtype
      reclassification rate after the addition of cardiac magnetic resonance imaging
      results to a diagnostic work-up which includes transesophageal echocardiography
      was very low. Prospective studies evaluating the role of cardiac magnetic
      resonance imaging and transesophageal echocardiography among patients with
      cryptogenic stroke should be considered.

PMID- 28436307
TI  - Choice of ANesthesia for EndoVAScular Treatment of Acute Ischemic Stroke:
      Protocol for a randomized controlled (CANVAS) trial.
AB  - : Background Observational studies indicate that the type of anesthesia, local or
      general, may be associated with the post-procedural neurological function in
      patients with acute ischemic stroke undergoing endovascular treatment. However,
      these results need further confirmation, and the causal relationship has not yet
      been established. Methods This is a randomized controlled equivalence trial.
      Permuted block randomization stratified by culprit vessels will be used. Six
      hundred and forty patients with acute ischemic stroke undergoing endovascular
      recanalization will be randomized one to one to receive either general anesthesia
      or local anesthesia. The primary endpoint is the modified Rankin scale at 90 days
      after endovascular treatment. The secondary endpoints are the peri-procedural
      mortality and morbidity. Discussion The study aims to determine the effects of
      anesthetic choice on neurological outcomes in patients with acute ischemic stroke
      undergoing intra-arterial recanalization. If the results are positive, the study
      will indicate that the type of anesthesia does not affect neurological outcome
      after endovascular treatment. TRIAL REGISTRATION: ClinicalTrial.gov identifier:
      NCT02677415.

PMID- 28436308
TI  - The different effects of intraoral vertical ramus osteotomy (IVRO) and sagittal
      split ramus osteotomy (SSRO) on mandibular border movement.
AB  - OBJECTIVES: This study investigated the different effects of intraoral vertical
      ramus osteotomy (IVRO) and sagittal split ramus osteotomy (SSRO) on mandibular
      border movement. METHODS: The participants included 22 patients receiving IVRO
      and 22 patients receiving SSRO who were treated at Okayama University Hospital.
      Their mandibular border movement was evaluated in three dimensions with 6 degrees
      of freedom using an optical recording system. RESULTS: A strong correlation
      between condylar and lower incisor movement was observed during maximum jaw
      protrusion and laterotrusion. Significant improvements in condylar and lower
      incisor movement were detected after orthognathic surgery during maximum jaw
      protrusion and laterotrusion in the IVRO group and during maximum jaw protrusion
      in the SSRO group. DISCUSSION: IVRO likely achieves greater improvement in jaw
      movement than SSRO. Therefore, the application of IVRO could be considered in the
      treatment of patients with jaw deformities featuring temporomandibular joint
      problems.

PMID- 28436309
TI  - Corticotropin-releasing hormone-binding protein and stress: from invertebrates to
      humans.
AB  - Corticotropin-releasing hormone (CRH) is a key regulator of the stress response.
      This peptide controls the hypothalamic-pituitary-adrenal (HPA) axis as well as a
      variety of behavioral and autonomic stress responses via the two CRH receptors,
      CRH-R1 and CRH-R2. The CRH system also includes an evolutionarily conserved CRH
      binding protein (CRH-BP), a secreted glycoprotein that binds CRH with
      subnanomolar affinity to modulate CRH receptor activity. In this review, we
      discuss the current literature on CRH-BP and stress across multiple species, from
      insects to humans. We describe the regulation of CRH-BP in response to stress, as
      well as genetic mouse models that have been utilized to elucidate the in vivo
      role(s) of CRH-BP in modulating the stress response. Finally, the role of CRH-BP
      in the human stress response is examined, including single nucleotide
      polymorphisms in the human CRHBP gene that are associated with stress-related
      affective disorders and addiction. Lay summary The stress response is controlled
      by corticotropin-releasing hormone (CRH), acting via CRH receptors. However, the
      CRH system also includes a unique CRH-binding protein (CRH-BP) that binds CRH
      with an affinity greater than the CRH receptors. In this review, we discuss the
      role of this highly conserved CRH-BP in regulation of the CRH-mediated stress
      response from invertebrates to humans.

PMID- 28436310
TI  - Synthesis and characterization of poly(N-vinylcaprolactam)-based spray-dried
      microparticles exhibiting temperature and pH-sensitive properties for controlled
      release of ketoprofen.
AB  - Poly(N-vinylcaprolactam) (PNVCL) and poly(N-vinylcaprolactam-co-acrylic acid)
      (poly(NVCL-co-AA)) were synthesized by solution-free radical polymerization and
      displayed thermo-responsive behavior, with lower critical solution temperatures
      (LCSTs) of 35  degrees C and 39  degrees C, respectively. The incorporation of AA
      unities made the poly(NVCL-co-AA) sensitive to both pH and temperature. They were
      exploited in this work in preparing microparticles loaded with ketoprofen via
      spray-drying to modulate the drug release rate by changing pH or temperature. The
      interaction between polymer and drug was studied using X-ray diffractometry,
      Raman spectrometry and scanning electron microscopy (SEM). The biocompatibility
      of pure polymers, free ketoprofen as well as the spray-dried particles was
      demonstrated in vitro by low cytotoxicity and a lack of nitric oxide production
      in macrophages at concentrations as high as 100 ug/ml. The release profile of
      ketoprofen was evaluated by in vitro assays at different temperatures and pH
      values. Drug diffusion out of PNVCL's hydrated polymer network is increased at
      temperatures below the LCST. However, when poly(NVCL-co-AA) was used as the
      matrix, the release of ketoprofen was primarily controlled by the pH of the
      medium. These results indicated that PNVCL and the novel poly(NVCL-co-AA) could
      be promising candidates for pH and temperature-responsive drug delivery systems.

PMID- 28436311
TI  - Role of 6-Mercaptopurine in the potential therapeutic targets DNA base pairs and
      G-quadruplex DNA: insights from quantum chemical and molecular dynamics
      simulations.
AB  - The theoretical studies on DNA with the anticancer drug 6-Mercaptopurine (6-MP)
      are investigated using theoretical methods to shed light on drug designing. Among
      the DNA base pairs considered, 6-MP is stacked with GC with the highest
      interaction energy of -46.19 kcal/mol. Structural parameters revealed that
      structure of the DNA base pairs is deviated from the planarity of the equilibrium
      position due to the formation of hydrogen bonds and stacking interactions with 6
      MP. These deviations are verified through the systematic comparison between X-H
      bond contraction and elongation and the associated blue shift and red shift
      values by both NBO analysis and vibrational analysis. Bent's rule is verified for
      the C-H bond contraction in the 6-MP interacted base pairs. The AIM results
      disclose that the higher values of electron density (rho) and Laplacian of
      electron density (?2rho) indicate the increased overlap between the orbitals that
      represent the strong interaction and positive values of the total electron
      density show the closed-shell interaction. The relative sensitivity of the
      chemical shift values for the DNA base pairs with 6-MP is investigated to confirm
      the hydrogen bond strength. Molecular dynamics simulation studies of G-quadruplex
      DNA d(TGGGGT)4 with 6-MP revealed that the incorporation of 6-MP appears to cause
      local distortions and destabilize the G-quadruplex DNA.

PMID- 28436312
TI  - Evaluation of the controlled grip force exertion tasks associated with age,
      gender, handedness and target force level.
AB  - INTRODUCTION: Force control of the hand is an essential factor for operating
      tools and moving objects. Therefore, a method for quantifying hand functionality
      more accurately and objectively is very important. METHODS: The present study
      included 60 healthy participants (30 elderly and 30 young adults) to evaluate the
      effects of age, gender and target force levels on tracking performance. Tracking
      performance was quantified by measuring the difference between target force
      levels and exerted force. RESULTS: Females exerted 59.6% of the maximum grip
      strength of males and the elderly group exerted 70.5% of maximum grip strength
      compared with the young group. The elderly group showed 3.1 times larger tracking
      error than the young group. There was a significant difference in females between
      the young and elderly groups, indicating age-related decline in hand function is
      more pronounced in females. The difference in grip force control ability between
      the elderly and young groups was significant at the low target force level (5%
      maximum voluntary contraction). CONCLUSIONS: The results of this study could be
      used for hand function evaluation guidelines. In addition, this study could be
      used as a tool for physiotherapy to improve hand function and prevent its decline
      in elderly people.

PMID- 28436313
TI  - Longitudinal thumbnail fissures due to erlotinib therapy for lung cancer.
AB  - While therapy with epidermal growth factor receptor inhibitors leads to
      meaningful clinical responses in several tumor types, it has also been linked
      with perplexing toxic effects. Skin effects of these agents such as generalized
      papulo-pustular rash, trichomegaly, fingertip fissures, xerosis, pruritus and
      paronichias are now well characterized. Though uncommon, nail atrophic changes
      have also been described in subjects treated with these classes of agents. We
      describe herein unusual longitudinal thumbnail fissures caused by erlotinib
      therapy for metastatic lung cancer. Unique features are bilateral thumbnail
      involvement and central location in the nail bed. This side effect of erlotinib
      has not been previously reported in the medical literature.

PMID- 28436314
TI  - Metabolomic approaches in the discovery of potential urinary biomarkers of drug
      induced liver injury (DILI).
AB  - Drug-induced liver injury (DILI) is a major safety issue during drug development,
      as well as the most common cause for the withdrawal of drugs from the
      pharmaceutical market. The identification of DILI biomarkers is a labor-intensive
      area. Conventional biomarkers are not specific and often only appear at
      significant levels when liver damage is substantial. Therefore, new biomarkers
      for early identification of hepatotoxicity during the drug discovery process are
      needed, thus resulting in lower development costs and safer drugs. In this sense,
      metabolomics has been increasingly playing an important role in the discovery of
      biomarkers of liver damage, although the characterization of the mechanisms of
      toxicity induced by xenobiotics remains a huge challenge. These new-generation
      biomarkers will offer obvious benefits for the pharmaceutical industry,
      regulatory agencies, as well as a personalized clinical follow-up of patients,
      upon validation and translation into clinical practice or approval for routine
      use. This review describes the current status of the metabolomics applied to the
      early diagnosis and prognosis of DILI and in the discovery of new potential
      urinary biomarkers of liver injury.

PMID- 28436315
TI  - Restenosis after carotid artery stenting.
AB  - As a common etiology for ischemic stroke, atherosclerotic carotid stenosis has
      been targeted by vascular surgery since 1950s. Compared with carotid
      endarterectomy, carotid angioplasty and stenting (CAS) is almost similarly
      efficacious and less invasive. These advantages make CAS an alternative in
      treating carotid stenosis. However, accumulative evidences suggested that the
      long-term benefit-risk ratio of CAS may be decreased or even neutralized by the
      complications related to in-stent restenosis (ISR). Therefore, investigating the
      mechanisms and identifying the influential factors of ISR are of vital importance
      for improving the long-term outcomes of CAS. As responses to intrinsic and
      extrinsic injuries, intimal hyperplasia and vascular smooth muscle cell
      proliferation have been regarded as the principle mechanisms for ISR development.
      Due to the lack of consensus-based definition and consistent follow-up protocol,
      the reported incidences of ISR after CAS varied widely among studies. These
      variations made the inter-study comparisons of ISR largely illogical. To
      eliminate restenosis after CAS, both surgery and endovascular procedures have
      been attempted with promising results. For preventing ISR, drug-eluting stents
      and antiplatelets have been proposed as potential solutions.

PMID- 28436316
TI  - First-in-man experience of self-expanding nitinol stents combined with drug
      coated balloon in the treatment of femoropopliteal occlusive disease.
AB  - Purpose The present study aimed to determine the safety and efficacy of a drug
      coated balloon inflated within a thin-strut self-expanding bare-metal stent in
      patients with severe and complex femoropopliteal occlusive disease. Methods This
      prospective study used the Pulsar-self-expanding stent and Passeo-18 Lux drug
      coated balloon in patients with severe and complex femoropopliteal occlusive
      disease. The primary endpoint was the 12-month primary patency, and the secondary
      endpoints included 24-month primary patency, assisted primary patency, secondary
      patency, and clinically associated target lesion revascularisation. Results The
      study included 44 patients (51 limbs). The mean age of the patients was 67.6 +/-
      10.2 years, with 73% men. Chronic limb severity was classified as Rutherford
      Category III in 41% of the patients, stage IV in 31%, and stage V in 27%. Lesions
      were predominantly Trans-Atlantic Inter-Society Consensus (TASC 2007) D (51%) and
      C (45%), with 32 (63%) chronic total occlusions. Procedural success was obtained
      in all cases. The mean lesion length was 200 +/- 74.55 mm (95% CI = 167.09
      208.01) with a mean number of stents per limb used of 1.57 +/- 0.70 (95% CI =
      1.37-1.76). Distal embolisation occurred in two patients. The primary patency
      rates at the 12- and 24-month follow-up were 94% (95% CI = 82.9-98.1) and 88%
      (95% CI = 75.7-94.5), respectively. The assisted primary was 94% (95% CI = 82.9
      98.1) and secondary patency was 96% (95% CI = 85.2-99.0) at 24-month follow-up.
      The cumulative stent fracture rate at the 24-month follow-up was 10%. Freedom
      from clinically driven target lesion revascularisation was 94% (95% CI = 83-98%)
      at 12-month follow-up and 88% (95% CI = 76-94%) at 24-month follow-up, with two
      patients requiring a bypass graft. Conclusion Our novel approach involving the
      combination of a thin-strut bare-metal stent and a drug-coated balloon may be
      safe and effective, with sustainable and promising clinical outcomes up to 24
      months after treatment.

PMID- 28436317
TI  - Endoureteral coil embolization of an ureteral arterial fistula.
AB  - Background Ureteral arterial fistulas are rare but potentially life threatening.
      We present a female who developed a ureteral arterial fistula following a right
      robotic nephrectomy. After several endovascular interventions to control the
      bleeding had failed, we approached the fistula through the right ureteral stump
      with coil embolization. Methods Coil embolization of the right ureteral stump was
      performed. We utilized a 6Fr * 45 cm sheath inserted through one of the
      cystoscope channels to cannulate the right ureteral orifice. We then performed a
      retrograde ureterogram. After, we were able to visualize full length of the
      ureter, ahd we began placing several 10-12 mm Nester coils to pack the ureter and
      tamponade the fistula for hemostasis. After the ureter was packed, we injected 1
      g of Vancomycin into the ureter. The sheath and cytoscope were removed and the
      patient did well and was sent to the recovery room. Results Postoperatively, the
      patient had no complaints of hematuria and her hemoglobin level remained
      unchanged. She was observed for a few days prior to being discharged to home. The
      patient's follow-up at six months revealed resolution of her hematuria.
      Conclusion Ureteral arterial fistula is a potentially life-threatening condition.
      Endovascular stenting has provided a safe, reliable alternative to open surgery.
      However, when endovascular options are not satisfactory, coil embolization of the
      ureteral stump may serve as a safe and effective alternative treatment for these
      cases.

PMID- 28436318
TI  - Ergosterol Peroxide: A Mushroom-Derived Compound with Promising Biological
      Activities-A Review.
AB  - Ergosterol peroxide (EP; 5alpha,8alpha-epidioxy-22E-ergosta-6,22-dien-3beta-ol)
      is a C28-sterol and a component of many medicinal mushrooms. Since its discovery
      nearly a century ago, many sources and biological effects of this compound have
      been described. Effects range from antimicrobial to cytotoxic to
      immunosuppressive and other activities. This review covers biological
      investigations of EP, its activities, and possible mechanisms of action. EP is a
      promising candidate for drug development and contributes to the health-promoting
      effects of medicinal mushrooms.

PMID- 28436319
TI  - In Vitro Antioxidant and In Vivo Hypolipidemic Effects of the King Oyster
      Culinary-Medicinal Mushroom, Pleurotus eryngii var. ferulae DDL01
      (Agaricomycetes), in Rats with High-Fat Diet-Induced Fatty Liver and
      Hyperlipidemia.
AB  - We investigated the effect of the culinary-medicinal mushroom Pleurotus eryngii
      var. ferulae DDL01 on oxidative damage in the liver and brain and a high-fat/high
      cholesterol-induced hyperlipidemic model. In in vitro studies, the water extracts
      of the fruiting bodies showed strong scavenging activities of DPPH (139.46 +/-
      3.2 MUg) and hydroxyl (139.46 +/- 3.2 MUg) radicals. Moreover, the extracts
      showed Fe2+ chelating and reducing abilities, as well as a large amount of
      polyphenols and an inhibitory effect on lipid peroxidation in the liver and brain
      tissues. The rats were fed a pellet diet (7.5 g/rat/day) containing P. eryngii
      var. ferulae DDL01 (PD) for 3 weeks. In the high-fat/high-cholesterol-induced
      hyperlipidemic rat model, administration of PD caused a significant decrease (P <
      0.05) in the levels of serum triacylglycerols, low-density lipoprotein
      cholesterol, very-low-density lipoprotein cholesterol, aspartate
      aminotransferase, and alanine aminotransferase and a significant increase (P <
      0.05) in the level of high-density lipoprotein cholesterol. PD administration
      significantly decreased high-fat/high-cholesterol-induced hepatic lipid
      accumulation. Treatment with the extracts (up to 500 MUg/mL) did not
      significantly affect the viability of HepG2 and 3T3-L1 cells. Our findings
      suggest that this mushroom has potential as an antiatherogenic dietary source in
      the development of therapeutic agents and functional foods.

PMID- 28436320
TI  - Antibacterial Activity of Desert Truffles from Saudi Arabia Against
      Staphylococcus aureus and Pseudomonas aeruginosa.
AB  - Medicinal mushrooms represent an unlimited source of polysaccharides with
      nutritional, antitumoral, antibacterial, and immune-stimulating properties.
      Traditional studies of epigeous higher Basidiomycetes have recently been joined
      by studies of hypogeous fungi and, in particular, of so-called desert truffles.
      With the aim to obtain novel agents against bacteria of clinical importance, we
      focused on the edible desert truffle mushrooms Tirmania pinoyi, Terfezia
      claveryi, and Picoa juniperi as sources of new antimicrobial agents. In
      particular, we investigated the in vitro antibacterial activity of acid-soluble
      protein extracts (aqueous extracts) of these 3 species against the Gram-positive
      human pathogenic reference strain Staphylococcus aureus ATCC 29213 and the Gram
      negative strain Pseudomonas aeruginosa ATCC 15442. The acid-soluble protein
      extracts of T. pinoyi and T. claveryi showed minimum inhibitory concentrations of
      50 MUg/mL against tested pathogens. We believe that such preliminary results are
      promising to obtain a valuable antibiotic alternative to fight antibiotic
      resistant pathogens.

PMID- 28436321
TI  - Screening of Bioactive Compounds of Medicinal Mushrooms Collected on Tunisian
      Territory.
AB  - This study is, to our knowledge, the first to investigate the pharmacological
      importance of wild Tunisian mushrooms. Ethanolic extracts of 5 Tunisian mushrooms
      Phellinus torulosus, Fomes fomentarius, Trametes versicolor, Pisolithus albus,
      and Fomitopsis pinicola-were collected from the Kroumirie Region (North Tunisia).
      The dry basidomes of mushrooms were extracted using ethanol and evaluated for
      total polyphenol, flavonoid, flavonol, tannin, proanthocyanidin, and anthocyanin
      content. In addition, their antioxidant activities were determined using 3 assays
      (testing 2,2-diphenyl-1-picrylhydrazyl [DPPH] radical scavenging, the reducing
      power of iron, and the iron-chelating power). Their antimicrobial activities were
      assessed against 8 bacterial species. The results revealed the presence of
      significant differences between the secondary metabolites and biological
      activities of the different tested extracts. In addition, significant
      correlations were observed between antioxidant activities and phenolic contents.
      Crude ethanol extracts prepared from basidomes of F. fomentarius and Ph.
      torulosus have higher total phenolic content and antioxidant activity per the
      DPPH and metal-chelating activity assays. The reducing power assay showed that
      the ethanolic extract of F. pinicola had the highest activity. Ethanolic extracts
      of the 5 mushrooms have antibacterial activity against the evaluated strains.

PMID- 28436322
TI  - Typification and Characterization of Trametes multicolor (Agaricomycetes), a
      Perspective Species of Medicinal Mushrooms.
AB  - Nomenclature revision and enlarged taxonomical descriptions are still needed for
      some well-known species whose interpretation is complicated by many nomenclature
      or taxonomical problems. The polyporoid fungus widely known as Trametes ochracea
      (= Coriolus zonatus) belongs to such a problematic group. At the same time,
      recent data show that this species, like its sister species T. versicolor, seems
      to be a perspective subject for fungal biotechnology and pharmacology. This
      article is devoted to stabilizing the nomenclature of the species in question via
      lectotypification and epitypification of Boletus multicolor. It will clarify the
      name T. multicolor as applied to this species is nomenclaturally correct and
      useful, free of further problems. An expanded species description and cultural
      characterization of epitype materials are presented.

PMID- 28436324
TI  - Identification of a New Fungal Pathogen Causing White Villous Disease on the
      Fruiting Body of the Culinary-Medicinal Mushroom Auricularia auricula-judae
      (Agaricomycetes) in China.
AB  - Auricularia auricula-judae is an edible and medicinal fungus ranking fourth in
      production among the edible fungi cultivated worldwide. White villous disease is
      rampant in Northeast China; it infects the fruiting bodies of A. auricula-judae
      by forming a white mycelial layer on its ventral side. The disease not only
      causes an unacceptable morphological appearance and a poor-quality product, but
      it also significantly reduces the yield. In this study, based on fungal
      morphology, ribosomal DNA internal transcribed spacer sequences, identification
      of species-specific primers, and the pathogenicity of the mycelia and spores, 2
      fungal pathogens were isolated and identified as Fusarium equiseti and F.
      sporotrichioides.

PMID- 28436323
TI  - New Germplasms of the Culinary-Medicinal Button Mushroom, Agaricus bisporus
      (Agaricomycetes): Two Wild Strains from the Tibetan Plateau (China).
AB  - Agaricus bisporus is one of the most important commercially cultivated culinary
      medicinal mushrooms worldwide. In China, most of the cultivated strains of the
      fungus were introduced from other countries and cultivated in the eastern
      provinces. In this study, 2 wild strains of A. bisporus, 2091 and 2094, isolated
      from fresh specimens collected from the Tibetan Plateau, were domesticated and
      cultivated alongside a commercial hybrid strain, As2796, in Lhasa, China, for
      comparison in order to provide new germplasms for cultivation. Basic
      characteristics, mushroom yield, dry weight, polysaccharide contents, and
      antioxidant activities of the tested strains were analyzed. Compared with strain
      As2796, the 2 wild strains displayed good values for mycelial growth, time to
      fruiting, mushroom yield, dry weight, and polysaccharide contents, and their
      basidiomata had distinct morphological characteristics (e.g., brown or pale brown
      caps with some white scales). In addition, the antioxidant activities (reducing
      power and DPPH radical scavenging effect) of strain 2094 were significantly
      higher than those of the other 2 strains. Domestication of the 2 wild strains
      would add more genetic variation into the germplasm of A. bisporus for
      cultivation, especially in China, and might help to address the problem inherent
      to the nearly monoculture crop lacking genetic diversity in China.

PMID- 28436325
TI  - Photoperiodic Responses and Characterization of the Cmvvd Gene Encoding a Blue
      Light Photoreceptor from the Medicinal Caterpillar Fungus Cordyceps militaris
      (Ascomycetes).
AB  - Light is a necessary environmental factor for production of conidia and pigment,
      formation of stroma, and development of Cordyceps militaris, a well-known edible
      and medicinal mushroom. In this study, an obvious rhythm loop was observed in
      certain strains of C. militaris under conditions of alternating 12-hour intervals
      of dark and light. A possibly related gene, Cmvvd, the homologue of the blue
      light photoreceptor of Neurospora crassa, was cloned from the genome of C.
      militaris. The protein CmVVD is predicted to be 203 amino acids in length and is
      characterized by the presence of a light, oxygen, or voltage domain. Analysis of
      the CmVVD sensor domain (light, oxygen, or voltage) suggested that it is a blue
      light receptor. Cysteine 108 is essential for the in vivo function of VIVID (VVD)
      in N. crassa photoadaptation. However, proline is in this position instead in all
      of the tested CmVVD proteins, suggesting that CmVVD may have a different function
      or may function in ways different from VVD in N. crassa. Genetic variation
      analysis of CmVVD in 6 representative strains indicated that 3 informative sites
      exist. Cmvvd messenger RNA was able to be induced by light, and the expression
      level increased over 10 times after irradiation and was maintained at high levels
      in the nascent fruiting body. The light-induced expression of Cmvvd was abolished
      in Cmwc-1 mutants, suggesting that the expression of Cmvvd is dependent on the
      photoreceptor CmWC-1 or on a functional CmWC-1/WC-2 complex. This article will
      help to open the still-unexplored field of circadian rhythms for this fungus.

PMID- 28436326
TI  - Evaluation and Characterization of Nutritive Properties of the Jelly Ear Culinary
      Medicinal Mushroom Auricularia auricula-judae (Agaricomycetes) from Nigeria.
AB  - This study investigated the nutritive properties of the culinary-medicinal
      mushroom Auricularia auricula- judae. From the analysis, among the major
      minerals, potassium was found in the highest concentration, with a value of
      172.03 +/- 8.62 mg/kg, whereas manganese had the highest concentration among
      trace elements, with a value of 1.66 +/- 0.11 mg/kg. Glutamic acid was the amino
      acid detected in the largest amounts in this study, with a value of 10.09 +/-
      1.86 mg/kg. Although glutamine and asparagine were not detected in this mushroom,
      cysteine and methionine had the lowest concentrations, with values of 0.34 +/-
      0.01 and 0.80 +/- 0.03 mg/kg, respectively. The predominant oil was 9,12
      octadecadienoic acid (Z,Z)methyl ester, with retention times of 21.246 and 21.715
      minutes, and comprising percentages of the total of 4.309 and 47.385,
      respectively.

PMID- 28436327
TI  - Mechanism of Glucose Regulates the Fruiting Body Formation in the Beech Culinary
      Medicinal Mushroom, Hypsizygus marmoreus (Agaricomycetes).
AB  - To understand the fruiting process of Hypsizygus marmoreus, a synthetic liquid
      medium (SLM) was optimized to induce fruiting body initiation. Dependent on the
      SLM, the effect of a monofactor (glucose) on the fruiting bodies of H. marmoreus
      was studied at different concentrations (10 and 40 g/L). Primordia appeared
      approximately 10 days earlier in low-glucose media (LGM) than in high-glucose
      media (HGM), whereas mature fruiting bodies formed on mushrooms approximately 7
      days earlier and more primordia developed into mature fruiting bodies when
      cultured in HGM. In addition, the morphogenesis of the primordia was clustered in
      HGM, which was different than what was observed in LGM. Furthermore,
      differentially expressed genes (DEGs) that encoded various proteins involved in
      cell structure, general metabolism, signal transduction, and transcription and
      translation were analyzed by transcriptome sequencing. Six DEGs were detected by
      quantitative reverse-transcriptase polymerase chain reaction, and the results
      were consistent with the altered patterns of gene expression revealed by the
      transcriptome. This study not only identifies new candidate genes involved in the
      development of H. marmoreus but also provides a new research platform for
      studying the development of other edible mushrooms.

PMID- 28436328
TI  - Potential of Stem Cells as Regenerative Medicine: From Preface to Advancements.
AB  - Regenerative medicine is an emerging field to find solutions to some of the most
      challenging medical problems of humans. Regenerative medicine has the potential
      to revolutionize the whole health care system, in dealing with conditions such as
      heart disease, emphysema, liver fibrosis, kidney disease, diabetes, and
      neurological disorders. Among the many challenges to bringing regenerative
      medicine to the clinic is the selection of the best cell types and reliable ways
      to expand the number of cells. Stem cells emerged as the best cell type for
      regeneration of different organs. This review covers the application of stem
      cells in different degenerative diseases.

PMID- 28436329
TI  - Molecular Mechanisms Underlying the Function Diversity of ArsR Family
      Metalloregulator.
AB  - The ArsR family of transcriptional regulators are widespread among microorganisms
      and are involved in various important cellular events, such as metal ion
      homeostasis, biofilm formation, primary and secondary metabolism, symbiosis,
      response to adverse condition, and virulence. Its N-terminus contains a winged
      helix-turn-helix DNA-binding domain that can repress or activate transcription by
      binding to downstream target promoters. With the increasing number of members in
      this family identified over the past few decades, the ArsR family members have
      been intensively explored. In this review, we summarize the function of ArsR
      family of transcriptional regulators and the mechanisms of metal-regulated gene
      expression.

PMID- 28436331
TI  - lep Expression and Its Role in Obesity and Type-2 Diabetes.
AB  - Obesity is metabolic disorder that increases the risk of diabetes, heart disease,
      and other metabolic syndromes in human beings. One sign of diabetes is increased
      blood glucose levels in the body. Glucose levels increase due to problems with
      insulin secretion or insulin resistance. Maturity onset of diabetes of the young
      is more common in adults and occurs due to insulin resistance. Both diabetes and
      obesity are major problems that are responsible for the death of millions of
      individuals every year, worldwide. Leptin, a 164-KDa hormone that is secreted by
      white adipose tissue, is a product of the lep gene. Mutation in lep decreases
      leptin concentration and increases obesity and type-2 diabetes mellitus. Leptin
      has been shown to produce positive effects on hunger, energy expenditure, and
      behavior and is thus useful in the treatment of obesity and type-2 diabetes.
      Leptin controls appetite through its effect on the hypothalamus in the brain.
      Both leptin and insulin regulate appetite, body weight, and glucose levels in the
      body.

PMID- 28436330
TI  - Association between Methionine Synthase Reductase A66G Polymorphism and Male
      Infertility: A Meta-Analysis.
AB  - The aim of this meta-analysis was to assess the methionine synthase reductase
      (MTRR) gene 66A>G polymorphism and male infertility susceptibility. Studies were
      identified in PubMed and Embase databases. An odds ratio (OR) was used to assess
      the relationship between MTRR 66A>G polymorphism and male infertility risk. A
      total of seven case-control studies containing 1438 patients and 1363 controls
      were enrolled in the meta-analysis. Our results showed that no association exists
      between the MTRR 66A>G polymorphism and male infertility risk in the total
      population (GG vs. AA: OR = 1.29, 95% confidence interval [CI] = 1.00-1.66; GA
      vs. AA: OR = 1.09, 95% CI = 0.92-1.30; dominant model: OR = 1.13, 95% CI = 0.96
      1.34; recessive model: OR = 0.83, 95% CI = 0.67-1.03). In a subgroup analysis by
      nationality, the 66A>G polymorphism was not associated with male infertility in
      both Asians and Caucasians. In a subgroup analysis stratified by male infertility
      type, significant association was found with oligoasthenozoospermia (OAT) (GG vs.
      AA: OR = 1.83, 95% CI = 1.24-269; GA vs. AA: OR = 1.36, 95% CI = 0.88-2.11;
      dominant model: OR = 1.51, 95% CI = 1.13-2.01; recessive model: OR = 0.62, 95% CI
      = 0.46-0.85). In summary, the present meta-analysis suggests that MTRR 66A>G
      polymorphism may be associated with OAT risk.

PMID- 28436332
TI  - Applications of Three-Dimensional Cell Cultures in the Early Stages of Drug
      Discovery, Focusing on Gene Expressions, Drug Metabolism, and Susceptibility.
AB  - Three-dimensional (3D) cell cultures represent advances in the way in which cells
      are grown in vitro, and they are gaining ground for a variety of applications.
      Advantages of 3D systems include reliable and realistic study endpoints. Cells
      grown in 3D conditions mimic in vivo conditions to an extent that is not possible
      with traditional 2D cell-culture methods. One major area in which 3D cell
      cultures have proven to make a difference is with drug discovery. The facets
      taken advantage of for drug discovery are the cells' complex microenvironment,
      including the production of extracellular matrices, altered gene expressions and
      their protein products, drug metabolism, and susceptibility to drugs when
      compared to 2D cultures. Altered protein and gene expressions are useful for drug
      target identification. The susceptibility of 3D cultured cells for drug-induced
      effects can be used to obtain realistic data in a dose-dependent manner that can
      aid in identifying effective drug dosage. This review presents the contributions
      of 3D cell cultures for drug discovery, taking into consideration gene and
      protein expressions, drug metabolism, and susceptibility to drugs as the major
      focus points.

PMID- 28436333
TI  - Epidemiology of Hepatitis C Infection in Pakistan: Current Estimate and Major
      Risk Factors.
AB  - In Pakistan, hepatitis C virus (HCV) is a major healthcare problem, with acute
      and chronic infections responsible for liver damage, cirrhosis, and
      hepatocellular carcinoma. Under the Human Development Index of the United
      Nations, Pakistan is ranked 134th of 174 countries due to its poor educational
      and health standards. This study was designed to study HCV and its genotype
      prevalence in different cities and provinces of Pakistan and describe the major
      routes of HCV transmission. Literature searches were performed in PubMed,
      Mendeley, and Google Scholar. Ninety different studies were screened for this
      review, ranging from those published during the years 2000 to 2013. By
      calculating the mean average of all studies, it was clear that HCV percentage
      prevalence in the adult population was 11.55%, blood donors 10.10%, pregnant
      women 4.65%, children 1.6%, patients with different diseases 24.97%, and
      injecting drug users had the highest prevalence at 51.0%. HCV genotype 3a
      prevalence was found to be 63.45%, the highest of all genotypes. The percentage
      prevalence of HCV found for all of the provinces was Punjab: 5.46%, Sindh: 2.55%,
      Khyber Pakhtoonkhaw: 6.07%, Balochistan: 25.77%, and federally administrated
      tribal areas: 3.37%. This study shows that the overall prevalence of HCV in the
      provinces of Pakistan is 8.64% and suggests that the major routes of HCV
      transmission are reuse of syringes and needles and unchecked blood transfusions.
      Awareness and economic growth are required to help decrease HCV infection and
      improve health standards in Pakistan.

PMID- 28436334
TI  - Acute HIV Infection: Advances in Mechanisms and Prophylactic Therapeutic
      Management.
AB  - Human infection by HIV is spreading rapidly. The spread of the virus is generally
      organized and transmission can be rectal, oral, or penile. Several types of cells
      are susceptible to viral invasion. The appearance of symptoms during infection
      can vary, but the presence of the virus can be confirmed by testing for the
      antigen p24. The ELISA test is used to detect viral p24 antigen and antiviral
      antibodies. This technique is approved for the purposes of clinical practice.
      Highly active antiretroviral therapy is usually a costly and lengthy treatment
      for HIV infection. A rapid point of care test has also been developed to detect
      acute infection. There is a need for preventing HIV infection and improving
      antiretroviral therapy. The treatment regime currently constitutes drugs that
      have the capability to concentrate in the genital tract of both males and
      females, as well as the use of integrase inhibitors that rapidly reduce viral
      load.

PMID- 28436335
TI  - Localization of the Werner Protein Together with H2AX in gamma-Irradiation
      Induced Neoplastic Transformed Human Mesenchymal Stem Cells.
AB  - The H2A histone family, member X (H2AX), and Werner (WRN) are important proteins
      for genome and telomere maintenance. WRN has a major role in genome stability,
      particularly during DNA replication, transcription, recombination, and repair of
      DNA double-stranded breaks (DSBs) via base excision repair, homologous
      recombination, or nonhomologous end joining. H2AX plays a part in the rapid,
      sensitive, cellular response to the ionizing radiation or DNA-damaging
      chemotherapeutic agents that cause DSBs. This occurs when radiation-induced DSBs
      trigger the activation of H2AX and begin the damage-repair process. In this
      study, we investigate the role and localization of WRN together with DNA damage
      marker H2AX at the radiation-induced damaged sides of both the telomere
      immortalized human mesenchymal stem cells (hMSCs) and hMSC-telomere 1 (hMSC
      telo1) and in control primary hMSCs. Phosphorylated H2AX and WRN immune staining
      enabled evaluation of overall genomic integrity and damage/repair. We used
      peptide nucleic acid-fluorescent in situ hybridization to visualize telomeric
      damage as a short-term effect. A high-level WRN signal was observed in both
      primary hMSCs and telomerase-immortalized hMSCs after the cells had been
      subjected to infrared radiation. Afterward, the irradiation level of the WRN
      signals decreased considerably, especially in later passages, and WRN was
      nondetectable in the latest passages of the hMSC Telo1 cells. Contrary to this
      finding, we found that levels of H2AX phosphorylation in hMSC-telo1 cells
      increased with time, especially at telomere sides, suggesting that cells with
      long telomeres and high telomerase activity have the advantage of maintaining
      genomic integrity. Evaluation of localization of WRN signals demonstrated that
      WRN does not leave the nucleolus after irradiation. We did not detect the WRN
      signal at the telomere sides, but we could detect H2AX at the telomeric sides.
      Thus, our overall data suggest that the WRN protein is not involved in
      irradiationinduced DNA damage/repair, even at telomeric sides in hMSC and hMSC
      telo1.

PMID- 28436336
TI  - CARDIOVASCULAR SCREENING OF YOUNG ATHLETES: A REVIEW OF ECONOMIC EVALUATIONS.
AB  - OBJECTIVES: Some experts have promoted preparticipative cardiovascular screening
      programs for young athletes and have claimed that such programs were cost
      effective without performing a critical analysis of studies supporting this
      statement. In this systematic review, a critical assessment of economic
      evaluations on these programs is performed to determine if they really provide
      value for money. METHODS: A systematic review of economic evaluations was
      performed on December 24, 2014. Web sites of health technology assessment
      agencies, the Cochrane database of systematic review, the National Health Service
      Economic Evaluation Database of the Cochrane Library, EMBASE, Medline, Psychinfo,
      and EconLit were searched to retrieve (reviews of) economic evaluations. No
      language or time restrictions were imposed and predefined selection criteria were
      used. Selected studies were critically assessed applying a structured data
      extraction sheet. RESULTS: Five relevant economic evaluations were critically
      assessed. Results of these studies were mixed. However, those in favor of
      screening made (methodological) incorrect choices, of which the most important
      one was not taking into account a no-screening alternative as comparator.
      Compared with no screening, other strategies (history and physical examination or
      history and physical examination plus electrocardiogram) were not considered cost
      effective. CONCLUSIONS: Results of primary economic evaluations should not be
      blindly copied without critical assessment. Economic evaluations in this field
      lack the support of robust evidence. Negative consequences of screening (false
      positive findings, overtreatment) should also be taken into account and may cause
      more harm than good. A mass screening of young athletes for cardiovascular
      diseases does not provide value for money and should be discouraged.

PMID- 28436337
TI  - Molecular cloning, expression, and characterization of E2F transcription factor 4
      from Antheraea pernyi.
AB  - The E2F transcription factor family is distributed widely in eukaryotes and has
      been well studied among mammals. In the present study, the E2F transcription
      factor 4 (E2F4) gene was isolated from fat bodies of Antheraea pernyi and
      sequenced. E2F4 comprised a 795 bp open reading frame encoding a deduced amino
      acid sequence of 264 amino acid residues. The recombinant protein was expressed
      in Escherichia coli (Transetta DE3), and anti-E2F4 antibodies were prepared. The
      deduced amino acid sequence displayed significant homology to an E2F4-like
      protein from Bombyx mori L. Quantitative real-time polymerase chain reaction
      analysis revealed that E2F4 expression was highest in the integument, followed by
      the fat body, silk glands, and haemocytes. The expression of E2F4 was upregulated
      in larvae challenged by bacterial (Escherichia coli, Micrococcus luteus), viral
      (nuclear polyhedrosis virus), and fungal (Beauveria bassiana) pathogens. These
      observations indicated that E2F4 is an inducible protein in the immune response
      of A. pernyi and probably in other insects.

PMID- 28436338
TI  - The effect of Boswellia serrata resin diet supplementation on production,
      hematological, biochemical and immunological parameters in broiler chickens.
AB  - Boswellia serrata resin (BSR), exhibiting a variety of therapeutic properties, is
      applied in Asian traditional medicine. These properties can be used in poultry
      production as well. Application of the resin as a phytobiotic in broiler chicken
      rearing can increase the productivity and improve meat quality. However, the
      optimum and maximum levels of BSR in broiler diets need to be assessed. The study
      determined the effect of different levels of supplementation of BSR (directly
      derived, unprocessed) in diets for broiler chickens on the production traits,
      selected slaughter analysis parameters, nutrient digestibility and selected
      hematological, biochemical and immunological parameters. In total, 200 1-day-old
      broiler chickens were assigned randomly to four treatments with five replicate
      cages of 10 broiler chickens/cage (five females and five males). The experiment
      lasted 6 weeks, and the broiler chickens were fed diets containing 0% (control),
      3% (BSR3), 4% (BSR4) or 5% (BSR5). In the broiler chickens receiving diets with
      addition of resin BSR3 and BSR4, there was an increase in (P<0.05) BW gain, ether
      extract, ADF, organic matter and energy digestibility of the diets. Moreover, the
      best carcass quality with a high proportion of muscles and low abdominal fat
      content (P<0.05) was noted in these groups. The content of uric acid (P<0.01) and
      the activity of aspartate aminotransferase (P<0.001) and alkaline phosphatase
      (P<0.05) in blood plasma decreased upon the BSR supplementation. Globulin content
      increased in blood plasma (P<0.05) along the increasing level of BSR. The blood
      immunoglobulin A concentration was only affected by the BSR treatments (P<0.05).
      It may be concluded that BSR can be regarded as a safe and effective dietary
      additive for broiler chicken.

PMID- 28436339
TI  - Cognitive sequelae of lithium intoxication: a case report.
AB  - Lithium intoxication is known to induce cognitive deficits along with motor and
      behavioral changes, even in association with normal serum levels. However, cases
      with comprehensive neuropsychological assessment of the deficits are rare. In our
      patient, we initially found severe cognitive deficits, including apraxia and
      visuo-constructive problems, and temporo-parietal FDG-PET hypometabolism.
      Neuropsychological and imaging findings were highly suggestive of Alzheimer's
      disease. However, lithium intoxication was suspected to account for these
      findings because of a Parkinson's syndrome, despite serum levels being in the
      upper therapeutic range. This was confirmed as cessation of lithium medication
      not only let the Parkinson's syndrome disappear, but also lead to dramatic
      improvements with respect to cognition.

PMID- 28436340
TI  - Racial inequality in the annual risk of Tuberculosis infection in the United
      States, 1910-1933.
AB  - Tuberculosis (TB) mortality rates in the USA fell rapidly from 1910 to 1933.
      However, during this period, racial disparities in TB mortality in the nation's
      expanding cities grew. Because of long delays between infection and disease, TB
      mortality is a poor indicator of short-term changes in transmission. We estimated
      the annual risk of TB infection (ARTI) in 11 large US cities to understand
      whether rising inequality in mortality reflected rising inequality in ARTI using
      city-level TB mortality data compiled by the US Department of Commerce from 1910
      to 1933. We estimated ARTI for African-Americans and whites using pediatric
      extrapulmonary TB mortality data for African-Americans and whites in our panel of
      cities. We also estimated age-adjusted pulmonary TB mortality rates for these
      cities. We find that the ratio of ARTI for African-Americans vs. whites increased
      from 2.1 (95% CI = 1.7, 2.4) in 1910 to 4.2 (95% CI = 3.4, 5.2) in 1933. This
      change mirrored the increasing inequality in age-adjusted pulmonary TB mortality
      during this period. These findings may reflect the combined effects of migration,
      inequality in access to care, increasing population density, and racial
      residential segregation in northern cities during this period.

PMID- 28436341
TI  - Insular pathology in young people with high-functioning autism and first-episode
      psychosis.
AB  - BACKGROUND: Autism Spectrum Disorders (ASD) and psychosis share deficits in
      social cognition. The insular region has been associated with awareness of self
      and reality, which may be basic for proper social interactions. METHODS: Total
      and regional insular volume and thickness measurements were obtained from a
      sample of 30 children and adolescents with ASD, 29 with early onset first-episode
      psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level
      volume and thickness measurements were compared between groups (with correction
      for multiple comparisons), and the relationship between these measurements and
      symptom severity was explored. RESULTS: Compared with HC, a shared volume deficit
      was observed for the right (but not the left) anterior insula (ASD: p = 0.007,
      FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011,
      FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry
      (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter
      volume and thickness deficit in the left posterior insula. Within patients, right
      anterior (r = -0.28, p = 0.041) and left posterior (r = -0.29, p = 0.030) insular
      volumes negatively correlated with the severity of insight deficits, and left
      posterior insular volume negatively correlated with the severity of 'autistic
      like' symptoms (r = -0.30, p = 0.028). CONCLUSIONS: The shared reduced volume and
      thickness in the anterior and posterior regions of the insula in ASD and FEP
      provides the first tentative evidence that these conditions share structural
      pathology that may be linked to shared symptomatology.

PMID- 28436343
TI  - Implications of feed concentrate reduction in organic grassland-based dairy
      systems: a long-term on-farm study.
AB  - In response to increasing efforts for reducing concentrate inputs to organic
      dairy production in grassland-rich areas of Europe, a long-term study was
      conducted, which assessed the impacts of concentrate reductions on cows'
      performance, health, fertility and average herd age. In total, 42 Swiss
      commercial organic dairy cattle farms were monitored over 6 years ('Y0', 2008/09
      until 'Y5', 2013/14). In comparison with overall data of Swiss herdbooks
      (including conventional and organic farms), the herds involved in the project had
      lower milk yields, similar milk solids, shorter calving intervals and higher
      average lactation numbers. During the first 3 project years farmers reduced the
      concentrate proportion (i.e. cereals, oilseeds and grain legumes) in the dairy
      cows' diets to varying degrees. In Y0, farms fed between 0% and 6% (dietary dry
      matter proportion per year) of concentrates. During the course of the study they
      changed the quantity of concentrates to voluntarily chosen degrees.
      Retrospectively, farms were clustered into five farm groups: Group '0-conc' (n=6
      farms) already fed zero concentrates in Y0 and stayed at this level. Group 'Dec
      to0' (n=11) reduced concentrates to 0 during the project period. Groups 'Dec
      strong' (n=8) and 'Dec-slight' (n=12) decreased concentrate amounts by >50% and
      <50%, respectively. Group 'Const-conc' (n=5 farms) remained at the initial level
      of concentrates during the project. Milk recording data were summarised and
      analysed per farm and project year. Lactation number and calving intervals were
      obtained from the databases of the Swiss breeders' associations. Dietary
      concentrate amounts and records of veterinary treatments were obtained from the
      obligatory farm documentations. Data were analysed with GLMs. Daily milk yields
      differed significantly between farm groups already in Y0, being lowest in groups
      0-conc (16.0 kg) and Dec-to0 (16.7 kg), and highest in groups Dec-slight (19.6
      kg) and Const-conc (19.2 kg). Milk yield decreases across the years within groups
      were not significant, but urea contents in milk decreased significantly during
      the course of the project. Milk protein, somatic cell score, fat-protein ratio,
      average lactation number, calving interval and frequency of veterinary treatments
      did not differ by group and year. In conclusion, 5 years of concentrate reduction
      in low-input Swiss organic dairy farms, affected neither milk composition, nor
      fertility and veterinary treatments. Milk yields tended to decline, but at a low
      rate per saved kilogram of concentrate.

PMID- 28436344
TI  - Inattention tests for delirium.
AB  - Voyer and colleagues (2016) report an interesting and important comparison of ten
      attention/concentration tests for DSM-5 delirium. I have a number of questions
      and comments as follows: (1) What training did the research assistants have? DSM
      5 diagnosis is generally regarded as a decision by medical specialists. When the
      person has prior dementia, identifying delirium is a high-level medical skill.
      Behavioral and psychological symptoms of dementia can closely mimic delirium
      unless the examiner focuses on behavioral triggers and the speed of cognitive
      decline. (2) The requirement of taking medications twice a day may have
      eliminated some delirium patients with impaired swallowing or refusal to take
      medications. (3) Lumping dementia, confusion, and disorientation into one label
      "cognitive impairment" is problematic and reduces the usefulness of Table 3. (4)
      The authors used prior diagnosis of dementia as a gold standard when in fact many
      people with that label have mild cognitive impairment. (5) The ten
      "concentration" subtests in the Hierarchic Dementia Scale (HDS) (Cole and
      Dastoor, 1987) are not purely indices of concentration. Serial seven subtraction
      is impaired in low education with normal concentration. Months of the year
      backwards is often ranked as both an attention and executive function test and it
      requires semantic knowledge. Digit span forward is a rapid attention test missing
      from the HDS which has been of great value in my delirium research. (6) As
      expected DSM-5 delirium was more common among medical inpatients than long-term
      care residents (14.9% vs. 4.0%, Table 1). (7) The Central Coast Australia
      Delirium Intervention Study (Regal, 2015) supported the gold standard to prove
      delirium was the speed and amplitude of both onset and recovery. In CADIS, the
      mean recovery of five-digit span forward was two days, six-DSF 5.6 days and
      Delirium Index 8.0 days.

PMID- 28436342
TI  - Comparison of neural substrates of temporal discounting between youth with autism
      spectrum disorder and with obsessive-compulsive disorder.
AB  - BACKGROUND: Autism spectrum disorder (ASD) and obsessive-compulsive disorder
      (OCD) share abnormalities in hot executive functions such as reward-based
      decision-making, as measured in the temporal discounting task (TD). No studies,
      however, have directly compared these disorders to investigate common/distinct
      neural profiles underlying such abnormalities. We wanted to test whether reward
      based decision-making is a shared transdiagnostic feature of both disorders with
      similar neurofunctional substrates or whether it is a shared phenotype with
      disorder-differential neurofunctional underpinnings. METHODS: Age and IQ-matched
      boys with ASD (N = 20), with OCD (N = 20) and 20 healthy controls, performed an
      individually-adjusted functional magnetic resonance imaging (fMRI) TD task. Brain
      activation and performance were compared between groups. RESULTS: Boys with ASD
      showed greater choice-impulsivity than OCD and control boys. Whole-brain between
      group comparison revealed shared reductions in ASD and OCD relative to control
      boys for delayed-immediate choices in right ventromedial/lateral orbitofrontal
      cortex extending into medial/inferior prefrontal cortex, and in cerebellum,
      posterior cingulate and precuneus. For immediate-delayed choices, patients
      relative to controls showed reduced activation in anterior cingulate/ventromedial
      prefrontal cortex reaching into left caudate, which, at a trend level, was more
      decreased in ASD than OCD patients, and in bilateral temporal and inferior
      parietal regions. CONCLUSIONS: This first fMRI comparison between youth with ASD
      and with OCD, using a reward-based decision-making task, shows predominantly
      shared neurofunctional abnormalities during TD in key ventromedial, orbital- and
      inferior fronto-striatal, temporo-parietal and cerebellar regions of temporal
      foresight and reward processing, suggesting trans-diagnostic neurofunctional
      deficits.

PMID- 28436346
TI  - DEVELOPMENT OF HEALTH TECHNOLOGY ASSESSMENT IN ROMANIA.
AB  - OBJECTIVES: The aim of this study was to describe and analyze the introduction of
      health technology (HTA) in Romania. METHODS: Based on a review of the literature
      and legislative documents and personal experiences and observations, the authors
      describe, evaluate, and explain the background and evolution of the HTA system.
      RESULTS: Initiatives to introduce HTA in Romania date from the early 1990s, but
      real steps were taken only in 2012 when the European Union Directive 2011/24/ on
      the application of patients' rights in cross-border health care had to be passed
      into Romanian law. The main developments consist of: the establishment of a
      national competent authority, the development of a methodology for the rapid
      assessment of drugs, setting HTA as the main tool for compiling the list of
      medicines to be covered by the NHIF, and capacity building initiatives. One early
      result of HTA implementation was an updated list of reimbursed drugs, allowing
      Romanian patients access to new, innovative medicines. CONCLUSIONS: In Romania,
      HTA become an issue for all stakeholders: decision makers are interested in cost
      containment, patients in obtaining the best care, and producers in receiving
      acceptable reimbursement remains on the health policy agenda. Further steps are
      envisaged, especially for international collaboration, which is considered an
      important factor for HTA development in Romania.

PMID- 28436345
TI  - Evidence that polygenic risk for psychotic disorder is expressed in the domain of
      neurodevelopment, emotion regulation and attribution of salience.
AB  - BACKGROUND: The liability-threshold model of psychosis risk predicts stronger
      phenotypic manifestation of the polygenic risk score (PRS) in the healthy
      relatives of patients, as compared with healthy comparison subjects. METHODS:
      First-degree relatives of patients with psychotic disorder (871 siblings and 812
      parents) and healthy comparison subjects (n = 523) were interviewed three times
      in 6 years. Repeated measures of two psychosis phenotypes, the Community
      Assessment of Psychic Experiences (CAPE; self-report - subscales of positive,
      negative and depressive symptoms) and the Structured Interview for Schizotypy -
      Revised (SIS-R; clinical interview - subscales of positive and negative
      schizotypy), were examined for association with PRS. Interview-based lifetime
      rate of depressive and manic episodes were also examined, as was association with
      repeated measures of intelligence quotient (IQ). RESULTS: In the relatives, PRS
      was associated with CAPE/SIS-R total score (respectively, B = 0.12, 95% CI 0.02
      0.22 and B = 0.11, 95% CI 0.02-0.20), the SIS-R positive subscale (B = 0.16, 95%
      CI 0.04-0.28), the CAPE depression subscale (B = 0.21, 95% CI 0.07-0.34), any
      lifetime affective episode (OR 3.1, 95% CI 1.04-9.3), but not with IQ (B = -1.8,
      95% CI -8.0 to 4.4). In the controls, similar associations were apparent between
      PRS on the one hand and SIS-R total score, SIS-R positive, SIS-R negative, any
      lifetime affective episode and, in contrast, lower IQ (B = -8.5, 95% CI -15.5 to 
      1.6). CONCLUSIONS: In non-ill people, polygenic risk for psychotic disorder is
      expressed pleiotropically in the domain of neurodevelopment, emotion regulation
      and attribution of salience. In subjects at elevated genetic risk, emerging
      expression of neurodevelopmental alterations may create floor effects, obscuring
      genetic associations.

PMID- 28436347
TI  - Familiality and Heritability of Fatigue in an Australian Twin Sample.
AB  - Familial factors have previously been implicated in the etiology of fatigue, of
      which a significant proportion is likely attributable to genetic influences.
      However, family studies have primarily focused on chronic fatigue syndrome, while
      univariate twin studies have investigated broader fatigue phenotypes. The results
      for similar fatigue phenotypes vary between studies, particularly with regard to
      sex-specific contributions to the heritability of the traits. Therefore, the
      current study aims to investigate the familiality and sex-specific effects of
      fatigue experienced over the past few weeks in an older Australian population of
      660 monozygotic (MZ) twin pairs, 190 MZ singleton twins, 593 dizygotic (DZ) twin
      pairs, and 365 DZ singleton twins. Higher risks for fatigue were observed in MZ
      compared to DZ co-twins of probands with fatigue. Univariate heritability
      analyses indicated fatigue has a significant genetic component, with a
      heritability (h 2) estimate of 40%. Sex-specific effects did not significantly
      contribute to the heritability of fatigue, with similar estimates for males (h 2
      = 41%, 95% CI [18, 62]) and females (h 2 = 40%, 95% CI [27, 52]). These results
      indicate that fatigue experienced over the past few weeks has a familial
      contribution, with additive genetic factors playing an important role in its
      etiology.

PMID- 28436348
TI  - Same, Same But Different? Cognitive Behavioural Treatment Approaches for
      Paediatric CFS/ME and Depression - CORRIGENDUM.

PMID- 28436349
TI  - Distress, Psychotic Symptom Exacerbation, and Relief in Reaction to Talking about
      Trauma in the Context of Beneficial Trauma Therapy: Perspectives from Young
      People with Post-Traumatic Stress Disorder and First Episode Psychosis.
AB  - BACKGROUND: Of young people with first episode psychosis (FEP), over half report
      exposure to childhood trauma and consequent co-morbid post-traumatic stress
      disorder (PTSD) or symptoms. Currently no evidence-based interventions exist for
      PTSD in FEP. Clinicians report concerns that trauma-focused interventions with
      young people with FEP could result in distress and symptom exacerbation. Scant
      research suggests that talking about trauma in therapy can be distressing for
      some people. AIMS: To explore young people's reactions to a trauma-focused
      treatment for PTSD in FEP. METHOD: Semi-structured interviews were conducted with
      eight participants (age 18-27 years) with co-morbid PTSD and FEP, after
      completing a trauma-focused intervention. Transcripts were analysed using an
      interpretative phenomenological approach. Participants' baseline and end-of
      treatment PTSD and psychotic symptoms were assessed. RESULTS: Three themes
      related to participants' reactions were identified from the analysis: (1)
      distress in session; (2) feeling relieved in and out of session; and (3) symptom
      exacerbation out of session. All but one participant reported experiencing
      increased distress in session. Four participants described PTSD, psychotic
      symptoms and/or suicidal ideation worsening in immediate reaction to talking
      about trauma in therapy sessions. 86% of participants showed improvement in their
      PTSD and psychotic symptoms at end of treatment. All participants described the
      intervention as beneficial and worthwhile. CONCLUSIONS: Results suggest that
      feelings of distress are to be expected from individuals with PTSD and FEP during
      trauma-focused treatment. Psychotic and PTSD symptom exacerbation can occur in
      PTSD treatment in FEP. Clinicians should be aware of, plan for, and clearly
      inform their clients of treatment risks.

PMID- 28436350
TI  - Prevalence and risk factors for gastric ulceration in pigs slaughtered at 170 kg.
AB  - Oesophago-gastric ulcers (OGU) are a production and welfare problem in pigs.
      Stomach condition was scored for 22 551 pigs in 228 batches over a 7-month period
      at an abattoir in Italy processing heavy pigs for ham production. Mild or severe
      ulceration was observed in 20.7% of pigs, of which 13% had scar tissue. Variation
      between batches was high (0% to 36% prevalence of severe ulcers) and showed a
      significant effect of farm of origin (P<0.001). Overnight lairage increased the
      prevalence of mild ulcers (P<0.001), but not severe or scarred ulcers. Scarred
      ulcers increased in the hottest summer months. Prevalence of ulcers showed only
      few and weak correlations at batch level with pathologies of the pleura, lungs
      and liver, but a strong correlation with on-farm mortality of the batch. Analysis
      of farm risk factors for OGU was assessed by questionnaire with a response rate
      of 17% of farms. Risk factors retained in a multivariable model included a
      protective effect of anthelmintic treatment (risk ratio (RR)=5.1, P=0.03),
      increased risk in farms using Mycoplasma vaccination (RR=5.6, P=0.04) and a
      tendency for association with type of flooring (P=0.06). Univariable analyses
      also highlighted possible influences of other stress-inducing factors including
      lack of enrichment objects and mixing of pigs during fattening, suggesting that
      the role of on-farm stressors merits further investigation. It is concluded that
      abattoir screening of OGU in future programmes for the assessment of well-being
      on farm should encompass only severe lesions and scarring, and results be
      returned to farmers to facilitate improvement of production and welfare.

PMID- 28436351
TI  - Reactivity to unpredictable threat as a treatment target for fear-based anxiety
      disorders.
AB  - BACKGROUND: Heightened reactivity to unpredictable threat (U-threat) is a core
      individual difference factor underlying fear-based psychopathology. Little is
      known, however, about whether reactivity to U-threat is a stable marker of fear
      based psychopathology or if it is malleable to treatment. The aim of the current
      study was to address this question by examining differences in reactivity to U
      threat within patients before and after 12-weeks of selective serotonin reuptake
      inhibitors (SSRIs) or cognitive-behavioral therapy (CBT). METHODS: Participants
      included patients with principal fear (n = 22) and distress/misery disorders (n =
      29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well
      validated threat-of-shock task was used to probe reactivity to predictable (P-)
      and U-threat and startle eyeblink magnitude was recorded as an index of defensive
      responding. RESULTS: Across both assessments, individuals with fear-based
      disorders displayed greater startle magnitude to U-threat relative to healthy
      controls and distress/misery patients (who did not differ). From pre- to post
      treatment, startle magnitude during U-threat decreased only within the fear
      patients who received CBT. Moreover, within fear patients, the magnitude of
      decline in startle to U-threat correlated with the magnitude of decline in fear
      symptoms. For the healthy controls, startle to U-threat across the two time
      points was highly reliable and stable. CONCLUSIONS: Together, these results
      indicate that startle to U-threat characterizes fear disorder patients and is
      malleable to treatment with CBT but not SSRIs within fear patients. Startle to U
      threat may therefore reflect an objective, psychophysiological indicator of fear
      disorder status and CBT treatment response.

PMID- 28436352
TI  - The Liquid Biopsy for Prostate Cancer 25 Years Later.

PMID- 28436353
TI  - Legends in Urology.

PMID- 28436354
TI  - What is the current role of partial nephrectomy for T2 tumors?
AB  - INTRODUCTION: To review oncological and functional outcomes for partial
      nephrectomy in the setting of T2 tumors. MATERIALS AND METHODS: We performed a
      comprehensive literature review on partial nephrectomy for T2 tumors, focusing on
      major primary series reporting oncological and functional outcomes, as well as
      complication rates in the last 10 years. RESULTS: Recent series have reported
      comparable oncological outcomes between partial nephrectomy and radical
      nephrectomy for >= T2 tumors. However, most of these studies are retrospective in
      design with small sample sizes. With regard to functional outcomes, partial
      nephrectomy outperforms radical nephrectomy. However, outcomes are dependent on
      the amount of residual renal parenchyma left after partial nephrectomy for larger
      tumors. Partial nephrectomy is associated with an increased rate of complications
      when compared to radical nephrectomy, but in experienced hands this increase
      tends to remain at an acceptable level. There are few studies that have
      investigated the role of minimally invasive surgery (MIS) in the setting of T2
      tumors. Although MIS techniques may be underutilized for management of T2 tumors,
      it is a feasible approach in highly selected patients. CONCLUSIONS: Partial
      nephrectomy has emerged as an acceptable alternative for surgical management of
      T2 renal tumors over the last decade. Nephron-sparing surgery demonstrates
      similar oncological outcomes compared to radical nephrectomy and can be
      considered even for larger tumors in carefully selected patients whenever
      feasible.

PMID- 28436355
TI  - Quantification of risk factors in 500 patients with postoperative urinary
      retention.
AB  - INTRODUCTION: An Institutional Quality and Safety Initiative to reduce
      postoperative urinary retention (POUR) and improve patient safety indicators
      (PSIs) was undertaken after a nurse driven protocol for catheter removal lead to
      an increase in POUR. The aim of this study was to identify the number of risk
      factors present in patients with POUR while examining the prevalence of those
      risk factors individually. MATERIALS AND METHODS: A retrospective review of our
      institution's surgical database was performed to identify 500 consecutive cases
      of POUR between July 1, 2013 and July 1, 2014. POUR was defined as the inability
      to void postoperatively with bladder scan volumes greater than 450 mL and
      subsequent need for catheterization with an output greater than 450 mL. These
      records were individually reviewed for 15 known independent risk factors for
      urinary retention. Patients with incomplete records or preoperative baseline
      urinary retention requiring catheterization were excluded. RESULTS: Of the 500
      consecutive patients with POUR, 288 (57.6%) were male and 212 (42.4%) were
      female. At the time of voiding trial, all 500 patients with POUR (100%) had at
      least one perioperative risk factor identified and over 75% had six or more (mean
      6.88, median 7, range 1-12). CONCLUSIONS: Multiple perioperative risk factors are
      present in the vast majority of patients with POUR. Many of the risk factors are
      modifiable and represent an opportunity for intervention. This could ultimately
      lead to a risk profile which could be used to optimize timing of postoperative
      voiding trials, thus improving patient care (improve PSIs and patient comfort,
      reduce trauma) while maintaining low rates of CAUTI.

PMID- 28436356
TI  - Association between natural killer cell activity and prostate cancer: a pilot
      study.
AB  - INTRODUCTION: Natural killer (NK) cells play a significant role in tumor cell
      immunosurveillance. The association between the activity of NK cells and prostate
      cancer has previously been demonstrated using conventional research-based tests.
      MATERIALS AND METHODS: The aim of the present pilot study was to study the
      association between NK cell activity (NKA) and prostate cancer using a simple
      blood test. Subjects that had previously been selected for prostate biopsy
      underwent a blood test for NKA using an in vitro diagnostic device (IVDD) (NK
      Vue, ATGen Canada Inc., Laval, QC, Canada) prior to biopsy. RESULTS: Of the 43
      subjects sent for prostate biopsy, 22 were found to have prostate cancer. The
      test performance of the NKA IVDD, assessed using receiver operating
      characteristics, showed an area under the curve of 75%, a sensitivity of 57%, a
      specificity of 91%, a positive predictive value of 86% and a negative predictive
      value of 69%, with an odds ratio of 13.33. Using a cut off of 200 pg/mL for NKA,
      the absolute risk of having prostate cancer with NKA values below this level was
      found to be 86%. CONCLUSIONS: This pilot study showed that subjects with low
      values of NKA were more likely to have a positive outcome at prostate biopsy.

PMID- 28436357
TI  - Prostate cancer detection following diagnosis of atypical small acinar
      proliferation.
AB  - INTRODUCTION: To report the incidence and characteristics of cancer following a
      diagnosis of atypical small acinar proliferation (ASAP) and comment on current
      clinical practice recommendations. MATERIALS AND METHODS: We reviewed patients
      that underwent prostate biopsy between 2008 and 2013 at a single institution. Men
      with ASAP without previous cancer were included. Clinicopathologic features
      including prostate-specific antigen (PSA), presence of ASAP or cancer, tumor
      volume, number of involved cores, and Gleason score were analyzed in men that
      received a repeat prostate biopsy. RESULTS: Of 1450 men, ASAP was found in 75
      (5%) patients. Repeat biopsy was performed in 49 (65%) patients. Fifteen (31%)
      were diagnosed with cancer, 10 (20%) with ASAP, and 24 (49%) were benign. PSA,
      age, and number of cores with ASAP were not associated with cancer. Gleason 6
      disease was diagnosed in 12 (80%) patients. Gleason >= 7 cancer was found in 3
      patients, or 6% of all patients with a repeat biopsy. The average linear amount
      of tumor was 3.2 mm, and the average tumor volume was 14.2%. CONCLUSION: In a
      contemporary prostate biopsy series, the incidence of ASAP was 5%. Among men with
      ASAP, incidence of cancer at repeat biopsy was 31%, with the overwhelming
      majority being low grade and low volume. Patients with ASAP may not require
      repeat biopsy within 6 months in the appropriate clinical context.

PMID- 28436358
TI  - A validation study of new decision algorithms for interpretation of cancer
      significance on prostate systematic biopsy.
AB  - INTRODUCTION: To test with actual data a new decision algorithm derived by
      probability modeling of the number of positive cores, for deciding insignificant
      versus significant prostate cancer, based on prostate volume, Gleason score,
      tumor length on biopsy cores, and number of positive cores. MATERIALS AND
      METHODS: A dataset of 59 cancer-involved autopsied prostate glands from patients
      aged 42 to 92 years with prostate volumes of 22 cc to 95 cc was used. An 18 core
      systematic biopsy was performed on the first 47 patients, and saturation biopsy
      protocol of 36 cores was performed on the remainder. Clinically insignificant
      prostate cancer was defined on whole-mount prostates as Gleason score < 7, total
      tumor volume <= 0.5 cc. Separate counts of 'significant' versus 'insignificant'
      prostate cancer by both the model-based decision algorithm and the actual data
      were obtained. These yielded specificity (SP), sensitivity (SE), and concordance
      values for evaluation of the efficacy of the decision algorithm. RESULTS: The
      model-based decision algorithm yielded SP from 83% to 100%, SE from 62% to 100%,
      and concordance from 78% to 100%. These findings compared favorably with those of
      currently used study-based algorithms and their individually fitted SP and SE
      derived from their corresponding studies. CONCLUSIONS: The model-based decision
      algorithm performed well with this dataset of autopsied prostates for patients
      with Gleason score 6 or lower, confirming its practical feasibility and its
      potential to help reduce over- and under-treatment, especially with marginally
      positive biopsy cases, by taking prostate volume properly into account. However,
      additional validation studies with other datasets including higher prostate
      volumes are needed for further calibration and improvement of the model-based
      decision algorithm.

PMID- 28436359
TI  - Robotic prostatectomy versus brachytherapy for the treatment of low risk prostate
      cancer.
AB  - INTRODUCTION: To compare oncological and functional results of robot-assisted
      radical prostatectomy (RARP) and brachytherapy (BT) with a single-center
      prospective randomized study. MATERIALS AND METHODS: From January 2012 to January
      2014, 165 patients with low risk prostate cancer, prostate volume <= 50 g, normal
      urinary (IPSS <= 7 and mean flow rate >= 15 mL/sec) and erectile functions (IIEF
      5 > 17) were enrolled and randomly assigned to the RARP or BT group. Our end
      points included the comparison of biochemical recurrence-free survival rates,
      urinary function (IPSS and EPIC scores) and potency rates (IIEF-5 score) at
      different time points during the first 2 years after surgery between the two
      groups. RESULTS: The biochemical recurrence-free survival rates were 96.1% and
      97.4% for the BT and RARP groups, respectively (p = 0.35). Significantly higher
      IPSS scores were assessed in the BT than in the RARP group at all the
      postoperative time points (p < 0.05). Significantly higher continence rates were
      assessed in the BT than in the RARP group during only the first 6 months of
      follow up (p < 0.05). Significantly lower potency rates were assessed in the BT
      than in the RARP group at all the postoperative time points (p < 0.05).
      CONCLUSIONS: Our data showed similar biochemical recurrence-free survival rates
      after BT and RARP. BT patients confirmed constantly higher rates of urinary
      symptoms while only reporting better continence rates for the first 6 months
      after surgery. RARP patients reported higher potency rates than BT patients
      during all the follow up period.

PMID- 28436360
TI  - Prostate cancer screening practices amongst physicians in the North Simcoe
      Muskoka Local Health Integration Network.
AB  - INTRODUCTION: The prostate-specific antigen (PSA) screening test is controversial
      and can result in both over-diagnosis and over-treatment. Recently, the Canadian
      Task Force on Preventive Health Care (CTFPHC) has recommended against routine
      screening for prostate cancer. We sought to determine how the CTFPHC has impacted
      the practice patterns among family physicians in the North Simcoe Muskoka (NSM)
      Local Health Integration Network (LHIN). MATERIALS AND METHODS: We surveyed all
      439 family physicians within the NSM LHIN as well as 21 residents of the Family
      Medical Teaching Unit. Surveys were distributed by either mail or fax. Questions
      covered three sections: 1) demographics, 2) screening practice, and 3)
      perceptions of screening efficacy. RESULTS: The overall survey response rate was
      33.3%. In all, 39.5% of physicians felt that prostate cancer screening did not
      provide a survival benefit, and 13.1% did not offer PSA screening. These beliefs
      were more likely to be held by younger physicians (age < 45), and those with < 10
      years of practice (p < 0.05). Interestingly, female physicians were less likely
      to believe that PSA screening provided a survival benefit (p <= 0.01); however,
      no gender bias for PSA screening practices was observed (p = 0.73). Of the
      physicians who agreed with CTFPHC's recommendation (31.8%), 6.0% do not offer PSA
      screening because of the recommendation. The CTFPHC recommendation had no impact
      on the age at which physicians begin or stop offering PSA screening (p > 0.05).
      CONCLUSION: Despite the CTFPHC recommendations, prostate cancer screening remains
      controversial. Practice patterns amongst general practitioners in the NSM LHIN
      vary considerably, but seem to have been minimally impacted.

PMID- 28436361
TI  - Robotic repair of vesicovaginal fistulas using fibrin sealant.
AB  - INTRODUCTION: Although infrequent, when encountered vesicovaginal fistulas (VVF)
      are a difficult condition for both patients and physicians alike. After the first
      robotic repair was described in 2005, this has been an increasingly common
      treatment modality. At our institution between 2009 and 2014, eleven of these
      patients were evaluated and treated with robotic repair. However, fibrin sealant
      was used in place of the traditional tissue flap. Included are six patients who
      had previously undergone operative repair. MATERIALS AND METHODS: After IRB
      approval was obtained, a retrospective study was undertaken to identify patients
      with VVF. Inclusion criteria were operative repair utilizing a da Vinci robotic
      system; there were no exclusion criteria. A total of eleven patients were
      identified, and in each case, a robot assisted laparoscopic approach was utilized
      and Tisseel fibrin sealant was used in lieu of tissue interposition. RESULTS: All
      patients underwent successful repair of their VVF without evidence of recurrence
      at a mean follow up of 15.6 months. CONCLUSIONS: Robotic vesicovaginal fistula
      repair with fibrin sealant seems to be a safe and viable alternative to the
      traditional repair utilizing a tissue flap.

PMID- 28436362
TI  - Comparative analysis of anticipated pain versus experienced pain in patients
      undergoing office vasectomy.
AB  - INTRODUCTION: Advances in vasectomy technique have minimized patient discomfort;
      however fear of pain remains a primary concern. The objective is to determine how
      the anticipation of pain associated with vasectomy compares with patient's actual
      intraoperative experienced pain levels. MATERIALS AND METHODS: A cohort of
      patients undergoing clinic vasectomy was analyzed. Using visual analog pain scale
      patients were asked to rate their anticipated pain score (APS) pre-procedure and
      then an experienced pain score (EPS) post-procedure. Patients were also
      stratified by APS scores (high versus low). Changes in pain score were compared
      across these groups. Pain scores stratified by age, race, narcotics use,
      psychiatric history, and prior surgical history were also compared. RESULTS: In
      the 172 patients included, the average pre-op APS was 5.2 (95% CI 4.3-5.6), while
      post-op EPS was 2.1 (95% CI 1.8-2.4). Patients were stratified into 'high' (6-10)
      and 'low' (0-5) pre-op APS groups. The average drop in pain scores was found to
      be significantly larger in the 'high' versus the 'low' APS groups (4.66 versus
      1.65 p < 0.001). No statistical difference was noted in the change in pain scores
      based on age, race, prior surgical history, chronic narcotics use or psychiatric
      history. Both groups tolerated the procedure well, with the mean EPS of 2.56 for
      the 'high' and 1.73 for the 'low' APS group (p < 0.05). CONCLUSIONS: The actual
      pain experienced by a patient is significantly lower than their anticipation of
      vasectomy pain, which will aid clinicians in appropriately counseling patients
      and minimizing pre-procedural anxiety.

PMID- 28436363
TI  - Supracostal punctures in supine percutaneous nephrolithotomy are safe.
AB  - INTRODUCTION: The feasibility and safety of supracostal punctures in supine
      percutaneous nephrolithotomy (PCNL) are still controversial. In this study we aim
      to compare success and complication rates from prone and supine PCNL with at
      least one supracostal puncture. MATERIAL AND METHODS: We reviewed our electronic
      database for all supracostal PCNLs performed in our institution from February
      2008 to September 2013. Patients were enrolled in the study if at least one
      supracostal puncture was required during surgery. Patients' demographics data,
      stone characteristics, intra and postoperative data, and success on first
      postoperative day CT were compared. RESULTS: A total of 132 procedures were
      included in the analysis. Twenty-eight PCNLs were performed in supine position
      (21.2%), while 104 were done in prone position (78.8%). Patient's demographics
      and distribution of stones based on Guy's Score were similar between groups. Mean
      operative time and blood transfusion rate were not statistically different. There
      was no significant difference in the success rate (63.5% prone versus 71.4%
      supine, p = 0.507). Major complication rate (Clavien >= 3) was 16.3% in the prone
      group versus 3.6% in the supine group (p = 0.119). CONCLUSIONS: Supracostal
      punctures are safe and feasible in supine PCNL. It does not add additional risks
      and might provide equivalent success rates when compared to prone PCNLs.

PMID- 28436364
TI  - Upper pole urologist-obtained percutaneous renal access for PCNL is safe and
      efficacious.
AB  - INTRODUCTION: Interventional radiologist may be hesitant to obtain upper pole
      access for percutaneous nephrolithotomy (PCNL) due to a higher complication rate.
      Renal access gained by urologists may achieve higher stone-free rates with
      similar complication rates. We evaluate our institution's contemporary results of
      percutaneous renal access in the upper pole for nephrolithotomy by urologists,
      which we believe both safe and efficacious. MATERIALS AND METHODS: This
      retrospective chart review included all PCNL's performed by fellowship-trained
      endourologists from 2003 to 2014 at a single institution. Inclusion criteria
      included patients in which renal access was obtained by the urologist via the
      upper pole for PCNL. Stone-free status was determined by either KUB or CT scan on
      POD #1. Patients without stones visible on KUB or less than 4 mm on CT were
      considered stone-free. RESULTS: A total of 144 patients obtained upper pole
      access for PCNL. There were a total of 53 (37%%) staghorn calculi, of which 35
      (66%) were partial staghorn stones. Renal access was obtained above 11th rib in
      12.5% (n = 18), between the 11th and 12th rib in 57.6% (n = 83), subcostal in
      14.6% (n = 21) and undetermined in the rest. Complications were seen in 18
      (12.5%) of patients. Hydropneumothorax requiring chest tube was seen in 8 (5.6%)
      patients. Postoperative imaging confirmed 93 (64.5%) patients stone-free, and 35
      (24.3%) required a second look PCNL. CONCLUSIONS: Our experience with upper pole
      percutaneous renal access for nephrolithotomy has shown that it has an acceptable
      complication risk. It should be a part of an endourologist's armamentarium that
      operate on large burden, complex stones or ureteral pathology.

PMID- 28436365
TI  - Adverse pathologic characteristics in the small renal mass: implications for
      active surveillance.
AB  - INTRODUCTION: Evidence has demonstrated that tumor size is related to adverse
      oncologic outcomes in small renal tumors (<= 4 cm). We evaluated the association
      of adverse pathologic features (APF) with tumor size and survival in patients
      with a small renal mass (SRM). MATERIALS AND METHODS: We retrospectively reviewed
      the pathologic characteristics of 380 surgically resected SRMs from a single
      institution. APFs included lymphovascular invasion, coagulative necrosis,
      sarcomatoid/rhabdoid features, papillary type II histology, and perinephric
      fat/renal sinus invasion. The number and type of APFs were compared with tumor
      size. Survival analysis was performed using the Kaplan-Meier method. RESULTS:
      There were 244 (64.2%) males and 136 (35.8%) females. The median age was 61
      years, and median tumor size was 2.7 cm. The median follow up time was 65 months.
      A significant association was found between tumor size and presence of APFs (p =
      0.018). At least 1 APF could be found in 22%, 32%, 36%, and 49% of tumors <= 1
      cm, 1 cm-2 cm, 2 cm-3 cm, and 3 cm-4 cm, respectively. There were no differences
      in overall survival or recurrence free survival when compared by tumor size at
      diagnosis (p = 0.22 and 0.15 respectively). Compared to patients with <= 1 APFs,
      disease specific survival was worse for patients with >= 2 APFs (p < 0.002).
      CONCLUSION: Our data support that aggressive tumor biology in a SRM is associated
      with greater size. In patients with a SRM, the decision to pursue active
      surveillance and the trigger for intervention should take tumor size and APFs
      into consideration as this may have future oncologic implications.

PMID- 28436366
TI  - Analysis of preoperative antibiotic prophylaxis in stented, distal hypospadias
      repair.
AB  - INTRODUCTION: Surgical site infection [SSI] is a risk for any surgical procedure,
      including hypospadias repair. Prophylactic antibiotic therapy for patients having
      surgery is often effective in preventing SSIs, but with increasing rates of
      antibiotic resistance, this practice has been questioned. The objectives of this
      study are 1) to assess the incidence of SSIs in patients following stented,
      distal hypospadias repair and 2) to observe for any potential difference in the
      incidence of SSIs for patients with and without preoperative antibiotic
      utilization in this setting. MATERIALS AND METHODS: We retrospectively reviewed
      consecutive patients treated with stented, distal hypospadias repair from 2011 to
      2014 by three surgeons and compared two groups: patients who received
      preoperative antibiotics and patients who did not. Patients with a history of
      previous hypospadias repair were excluded from the study. RESULTS: Two hundred
      twenty-four subjects were identified. Group 1 (135) received preoperative
      antibiotic and Group 2 (89) did not receive preoperative antibiotics. There was
      no statistically significant difference in SSI prevalence with 0 patients in
      Group 1 and 1 patient in Group 2 having a SSI. CONCLUSION: Although prophylactic
      antibiotics prior to hypospadias repair are most often used by pediatric
      urologists, this study demonstrates further evidence that antibiotics prior to
      this procedure do not appear to lower the rate of SSI. This study is limited by
      its retrospective nature and disparate mean follow up in the two cohorts.
      Surgical site infection does not appear to be decreased by prophylactic
      antibiotic therapy before distal hypospadias repair.

PMID- 28436367
TI  - Bilateral obstructing ureteric calculi in pregnancy: a rare cause of acute renal
      failure.
AB  - Bilateral obstructing ureteric calculi is a rare cause of acute renal failure.
      Although urolithiasis in later pregnancy is not uncommon, the development of
      bilateral obstruction secondary to ureteric calculi in the first trimester is
      rare and poses difficulty to diagnosis and management. Symptoms of diseases and
      physiological changes associated with pregnancy can obscure diagnosis of
      urolithiasis and obstructive uropathy. Advances in minimally invasive endourology
      afford intervention with reduced risk to fetal health. We present the second case
      of acute renal failure caused by bilateral obstructing ureteric calculi in a
      pregnant patient and discuss current management algorithms for this group.

PMID- 28436368
TI  - 'Pseudo' pseudoaneurysm following robotic assisted partial nephrectomy.
AB  - A 65-year-old female presented to clinic requesting follow up for a history of
      right robotic partial nephrectomy done at an outside institution 2 years prior.
      Initial pathology demonstrated a grade 2/4 3.4 cm clear cell renal cell carcinoma
      with negative margins. There was no tumor necrosis, sarcomatoid differentiation,
      or lymphovascular invasion. High quality follow up imaging initially revealed a
      pseudoaneurysm in the central portion of the right kidney. The patient was sent
      to interventional radiology for angioembolization. Angiography identified the
      abnormality to be a recurrent or residual mass in the renal hilum. MRI confirmed
      these findings, and the patient ultimately required a laparoscopic radical
      nephrectomy for definitive treatment. Final pathology showed grade 2/4 clear cell
      renal cell carcinoma with negative margins and no tumor necrosis or sarcomatoid
      differentiation. The tumor did involve sinus fat and sinus vessels, but not
      perinephric fat.

PMID- 28436369
TI  - Treating male retention patients with temporary prostatic stent in a large
      urology group practice.
AB  - Men with either chronic or temporary urinary retention symptoms are common
      patients treated in a urology practice. Both indwelling and intermittent
      catheterization are widely used to treat this condition. These approaches are
      associated with significant complications including infection and reduced quality
      of-life. Infection is a target for quality improvement and cost reduction
      strategies in most care settings today. We use a temporary prostatic stent (TPS)
      to address these issues in our practice. In this report, we describe our approach
      to patient selection, sizing, placement and follow up of 214 TPS placed in 56 men
      with chronic or temporary urinary retention in an office setting. With the first
      stent placement, average indwelling time was 27 days. Thirty-two patients had
      multiple stents placed. Replacement was performed routinely and was generally
      required because underlying comorbidities precluded surgery. In these patients,
      an average of six stents were placed (range 2-18) with average dwell times of 31
      days. Symptomatic urinary tract infections (SUTI) occurred in only 6 of 214 TPS
      placements (2.8%), resulting in an incident rate of 0.93 SUTI per 1,000 TPS days.
      TPS is a safe and efficacious means of alleviating symptoms of urinary retention.
      TPS does not share the same infection risk profile or quality-of-life drawbacks
      associated with urinary catheters; this makes TPS use relevant as a urinary
      catheter alternative or when a urinary catheter is not recommended.

PMID- 28436370
TI  - Clinical Neuropathology image 3-2017: CNS involvement in systemic amyloidosis
      restricted to the choroid plexus.

PMID- 28436371
TI  - Pigmented Villonodular Synovitis - Various Manifestations, Inconsistent
      Terminology and Treatment. Cases Study.
AB  - Pigmented villonodular synovitis (PVNS) as well as tenosynovial giant cell tumor
      (TGCT) are both diagnosed and described in two forms, namely a localized and
      diffuse type. They form a diverse group of proliferative lesions in articular
      synovium and tendon sheaths. The inconsistent terminology impedes communication
      between patients, orthopedic surgeons, radiologists and pathologists, leading to
      misunderstandings and delaying treatment. In this paper, we present three cases
      of PVNS/TGCT (involving the fourth toe extensor tendon sheath, hip joint after
      resurfacing and flexor hallucis longus tendon sheath) together with suggestions
      regarding the unification of the terminology as well as diagnosis and treatment.

PMID- 28436372
TI  - Unusual Location of Osteoid Osteoma in the Acromion.
AB  - We present the clinical case of a 14-year-old female patient complaining of
      omalgia. A focus of osteoid osteoma located in the acromion was diagnosed. The
      lesion was removed using the arthroscopic technique, and the symptoms subsided
      completely. We also present a review of published papers regarding unusual
      locations of osteoid osteoma.

PMID- 28436373
TI  - FATCO Syndrome (Fibular Aplasia, Tibial Campomelia, Oligosyndactyly with Talar
      Aplasia). A Case Study.
AB  - FATCO syndrome consists of fibular hemimelia, tibial campomelia and
      oligosyndactyly. FATCO syndrome can also be associated with other congenital
      anomalies; therefore, every case needs thorough evaluation so as to make the
      management of the patient easier. A few cases of this syndrome have been
      described in literature but only two cases have been reported in India so far. We
      present a 3-year-old male child born of a non-con-sanguinous marriage with FATCO
      syndrome and ipilateral talar aplasia without any other congenital anomalies.

PMID- 28436374
TI  - Factors Influencing Treatment of Proximal Femoral Fractures.
AB  - BACKGROUND: Orthopaedics and traumatology departments are dominated by patients
      with proximal femoral fractures, who represent 20-30% of all patients treated
      there. The aim of this study was identification and evaluation of factors
      influencing treatment of proximal femoral fractures. MATERIAL AND METHODS:
      Between 2008 and 2015, we treated 424 femoral neck fractures and 442 trochanteric
      fractures in patients over 40 y/o. The impact of fracture location (femoral
      neck/trochanteric), character (non-displaced/displaced) and the patient's general
      condition (metrical/biological age, health condition) on qualification and
      treatment used (fixations/hip pro-sthesis/non-operative) was analyzed. RESULTS:
      The results show a significant impact of factors such as type of fracture and
      general health condition on treatment method selection (mainly in femoral neck
      fractures). The distinction between non-displaced and displaced fractures is
      significant in preoperative qualification. For displaced femoral neck fractures,
      total hip replacement (non-cemented) was performed in patients between 55 and 65
      y/o, while total hip replacement (cemented) and hemiarthroplasty (bipolar/Austin
      Moore's) in patients between 75 and 90 y/o. In lateral fractures of the femoral
      neck, mostly total hip replacement and occasionally proximal femoral nail
      fixation was performed. The importance of qualification factors was much lower in
      preoperative qualification of trochanteric fractures, where internal fixation
      remains the primary method of treatment and total hip replacement was only used
      in patients with co-existing coxarthrosis. CONCLUSIONS: 1. The biggest impact on
      selection of femoral neck fractures treatment method was exerted by the degree of
      displacement of bone fragments, age and the patient's pre-injury walking status.
      2. Besides general condition, the presence of coxarthrosis was the most important
      factor influencing trochanteric fracture treatment method.

PMID- 28436375
TI  - Evaluation of Treatment of Low-energy Distal Radial Fractures in Postmenopausal
      Women.
AB  - BACKGROUND: Distal radial fractures are one of the most common injuries seen in
      traumatology. Most are treated conservatively with closed reduction and
      immobilisation in a plaster cast. However, this method does not always allow for
      achieving and maintaining normal fracture reduction in unstable fractures. The
      aim of this study was assess clinical and radiographic outcomes of treatment of
      distal radial fractures depending on the method used. MATERIAL AND METHODS: A
      total of 77 postmenopausal female subjects were divided into three subgroups,
      depending on the treatment methods: 1. closed reduction and immobilisation in a
      plaster cast; 2. closed reduction and percutaneous fixation with K wires; 3. open
      reduction and fixation with a locking plate. Follow-up examinations took place at
      4 and 12 months post injury and involved measurements of the range of motion in
      the radiocarpal joint and hand grip strength. The results were classified
      according to the Mayo Wrist Score. X-ray images were used to mark parameters of
      radiographic assessment of the distal radius and the results were classified
      according to the radiographic Lidstrom score. RESULTS: The percentage of
      excellent and good results was significantly higher in both surgically treated
      groups (plate: 92.6%, K wires: 88.0%) than in the group treated conservatively
      (48%). CONCLUSION: 1.The percentage of excellent and good results from both
      surgically treated groups (plate: 92.6%, K wires: 88.0%) was significantly higher
      than in the group treated conservatively (48%). 2. Open reduction with locking
      plate fixation of distal radial fractures produces better functional outcomes in
      the early postoperative period and reduces the risk of development of complex
      regional pain syndrome.

PMID- 28436376
TI  - Carpal Tunnel Syndrome: Symptoms, Causes and Treatment Options. Literature
      Reviev.
AB  - Carpal Tunnel Syndrome (CTS) is the most common form of entrapment neuropathy.
      Several authors have investigated the anatomical and pathophysiological features
      of CTS and have identified several parameters that, in combination, play a
      significant role in its pathophysiology. Advancement in biological research on
      CTS has enabled the advent of efficient diagnostic techniques such as provocative
      tests and nerve conduction studies. Sophisticated technologies, such as magnetic
      resonance imaging (MRI) and ultrasonography (US), have facilitated the diagnosis
      of CTS. This review article aims at consolidating the relevant medical literature
      pertaining to the symptoms, pathophysiology, clinical diagnosis and treatment
      strategies of CTS. It also compares the various methods of diagnosis and
      discusses their benefits and disadvantages. Finally, it sheds light on the
      conservative vs. surgical approach to treatment and compares them. While the
      surgical approach has proved to be more efficient relative to the conservative
      methods of steroid injections and splinting, many studies have demonstrated both
      advantages and adverse effects of the surgical methods. Surgical options and
      complications are discussed in detail. This article comprehensively summarizes
      all medical aspects of CTS to update medical professionals' knowledge regarding
      the disease.

PMID- 28436377
TI  - Analysis of Therapeutic Effectiveness of Selected Types of Collagen in Prevention
      and Treatment of Degenerative Joint Disease.
AB  - Loss of collagen is a natural development accompanying aging of the body. It may
      be additionally accelerated by various conditions, including osteoarthritis (OA).
      Within the last two decades numerous and diverse studies have been conducted
      worldwide with the aim of identifying substances containing collagen, producing
      therapeutic preparations of expected effectiveness in the prevention and therapy
      of OA that would be safe to use and developing methods of delivering the final
      product into the body. The authors reviewed and analysed the latest available
      literature by selecting papers presenting the findings of studies conducted in
      line with the principles of Evidence-Based Medicine (EBM). The studies have been
      ordered from in vitro trials (studies on animals in the laboratory setting, use
      of tissue engineering methods to assess the effect of cartilage transplants, use
      of different collagen types for development of scaffolds etc.) to in vivo
      clinical trials. It appears that the findings of the latest multidimensional
      studies presented below, which confirm the therapeutic effectiveness of new
      generation injectable medical collagen preparations, will help these medical
      products gain their well-deserved position in the comprehensive treatment of
      osteoarthritis both with respect to their analgesic properties as well as their
      ability to enable functional recovery and stimulate regeneration of tissues at
      the molecular level.

PMID- 28436378
TI  - Outcomes of Corpectomy in Patients with Metastatic Cancer.
AB  - BACKGROUND: The objective of surgical management of spinal metastases is to
      reduce pain and improve the patient's quality of life. The operation should
      restore spinal stability and decompress neural structures. One surgical technique
      is corpectomy followed by vertebral body reconstruction and stabilisation of the
      spine. The procedure may be performed in patients in overall good health and a
      good survival prognosis. The aim of this paper is to present the outcomes of
      surgical management of spinal metastases in patients who underwent corpectomy
      followed by vertebral body reconstruction and stabilisation of the spine.
      MATERIAL AND METHODS: The aim of the study was achieved by analysing medical
      histories of 124 patients with spinal metastases treated in the Oncological
      Orthopaedics Department in Brzozow in the period 2010-2015. The majority of
      patients in the group were women, who represented 64% of all the subjects. The
      average age was 63 years for women and 67 for men. The metastases were most
      frequently produced by breast cancer (36%) and myeloma (22%). A total of 87% of
      the group were diagnosed with pathologic fractures and 92% had spinal
      instability. Stenosis of the spinal canal was found in 78% of the patients. The
      surgeries were performed in 18 persons with metastases to the cervical spine, 69
      patients with metastases to the thoracic spine and 37 participants with
      metastases to the lumbar spine. Single-level corpectomies were performed in 83
      patients and multilevel corpectomies in 41 persons. Parameters analysed comprised
      overall health condition, neurological function (the Frankel Grade) and
      performance status (the Karnofsky score) of the patients. A VAS was used to
      assess the intensity of pain. The course of the operation and complications were
      also analysed. RESULTS: Following the surgeries, the average VAS pain score
      decreased from 7.2 to 3.8. Performance improved from a Karnofsky score of 50.26
      to 68.65. Neurological function improved in 21 out of 34 patients with pareses.
      The average duration of the surgery was 67 minutes for the cervical spine, 123
      minutes for the thoracic spine and 112 minutes for the lumbar spine. The loss of
      blood was strongest for lumbar spine surgeries, amounting on average to 580 ml.
      62% of patients required transfusion ofblood substitutes after the operation. The
      average hospitalisation time was 14 days, with a minimum and maximum duration of
      7 and 24 days, respectively. The most common complication was damage to the
      endplate of the vertebra adjacent to the prosthesis (11%). Two patients developed
      complete and irreversible paralysis of lower limbs. CONCLUSIONS: 1. Corpectomy
      followed by vertebral body reconstruction should be used in patients with a good
      prognosis. 2. Therapeutic outcomes are good. The surgery produced a considerable
      reduction in pain and improvement in performance in the majority of patients. 3.
      Complications are not frequent. The most common complication is intrusion of the
      implant into the endplate of the adjacent vertebrae. 4. A high survival rate at
      one year after the surgery, exceeding 90% of the patients, is evidence of
      effectiveness of the treatment and appropriate qualification of patients for the
      operation.

PMID- 28436379
TI  - Economic Analysis of 4221 Revisions Due to Periprosthetic Joint Infection in
      Poland.
AB  - BACKGROUND: Periprosthetic joint infection (PJI) is one of the most severe
      complications of total hip (THA) and total knee (TKA) arthroplasty. The aim of
      the study is to determine the number and type of hip and knee prosthesis
      revisions in Poland performed due to infection and reimbursement of the cost of
      septic revisions and to compare the costs of septic and aseptic revisions in
      Poland and other countries. MATERIAL AND METHODS: The data published for the
      period 2009-2013 by the National Health Fund (NHF) were analysed and the average
      cost of septic and aseptic revisions was calculated. RESULTS: In the years 2009
      2013, a total of 260,030 hip and knee arthroplasties including 23,027 revisions
      (incl. 4,221 septic) were performed in Poland. In 2013, septic revisions
      accounted for 1.38% of all hip replacement procedures, 2.56% of all knee
      replacement procedures and 14.67% of all hip revisions and 30.23% of all knee
      revisions. In 2013, the difference between the average cost incurred by the
      hospital and the NHF refund for septic revision due to PJI was at least ?238 and
      the cost-refund gap for the entire year was ?219198. CONCLUSION: 1. The system of
      reporting periprostheticjoint infections currently in use in Poland does not
      adequately reflect the current classification of PJI and reimbursement for septic
      revision of joint prosthesis does not match the actual costs. 2. The Polish DRG
      system does not distinguish between early and late PJI and fails to acknowledge
      basic guidelines for infection treatment currently followed in Poland and
      worldwide. 3. According to the DRG system, patients requiring different treatment
      are placed in one category. 4. Until the year 2013, the less expensive treatment
      of early infections had been reimbursed on the same basis as the more costly two
      stage revision procedures.

PMID- 28436380
TI  - Tenofovir disoproxil fumarate monotherapy is superior to entecavir-adefovir
      combination therapy in patients with suboptimal response to lamivudine-adefovir
      therapy for nucleoside-resistant HBV: a 96-week prospective multicentre trial.
AB  - BACKGROUND: A complete virological response is closely related to the long-term
      outcome of patients with chronic hepatitis B and prevention of emerging HBV
      mutations. We aimed to evaluate the efficacy of tenofovir disoproxil fumarate
      (TDF) monotherapy compared to entecavir-adefovir dipivoxil (ETV-ADV) combination
      therapy in patients with suboptimal responses to long-term lamivudine-adefovir
      dipivoxil (LAM-ADV) therapy for nucleoside analogue-resistant chronic hepatitis
      B. METHODS: Patients (n=60) were randomized to TDF monotherapy or ETV-ADV
      combination therapy for 96 weeks. All patients had the rt204I/V mutation and
      serum HBV DNA was measured (>60 IU/ml) during LAM-ADV therapy. The primary end
      point was a complete virological response (HBV DNA <20 IU/ml) at week 96.
      RESULTS: The median duration of prior LAM-ADV rescue therapy was 43 (7-108)
      months. A complete virological response was achieved in 86.6% and 53.3% of
      patients in the TDF and ETV-ADV groups, respectively, at week 96 (P=0.005).
      Reduction in serum HBV DNA was significantly greater in the TDF group than in ETV
      ADV group (-3.2 +/-1.2 versus -2.6 +/-1.2; P=0.01). Hepatitis B e antigen loss
      (22.2% versus 16.6%; P=0.731) and biochemical responses (76.7% versus 73.3%;
      P=0.766) were not different between the TDF and ETV-ADV groups. No newly emerged
      mutations were detected. Both therapies demonstrated favourable safety profiles.
      CONCLUSIONS: TDF therapy achieved a better complete virological response than ETV
      ADV therapy in chronic hepatitis B patients with suboptimal response to long-term
      LAM-ADV rescue therapy. (KCT0000627).

PMID- 28436381
TI  - Absorption and transmission of light in III-V nanowire arrays for tandem solar
      cell applications.
AB  - III-V semiconductor nanowires are a platform for next-generation photovoltaics.
      An interesting research direction is to embed a nanowire array in a transparent
      polymer, either to act as a stand-alone flexible solar cell, or to be stacked on
      top of a conventional Si bottom cell to create a tandem structure. To optimize
      the tandem cell performance, high energy photons should be absorbed in the
      nanowires whereas low energy photons should be transmitted to and absorbed in the
      Si cell. Here, through optical measurements on 1.95 eV bandgap GaInP nanowire
      arrays embedded in a polymer membrane, we identify two mechanisms that could be
      detrimental for the performance of the tandem cell. First, the Au particles used
      in the nanowire synthesis can absorb >50% of the low-energy photons, leading to a
      <40% transmittance, even though the Au particles cover <15% of the surface area.
      The removal of the Au particles can recover the transmission of low energy
      photons to >80%. Second, after the removal of the Au particles, a 40% reflectance
      peak shows up due to resonant back-scattering of light from in-plane waveguide
      modes. To avoid the excitation of these optical modes in the nanowire array, we
      propose to limit the pitch of the nanowire array.

PMID- 28436382
TI  - Template-free fabrication of graphene-wrapped mesoporous ZnMn2O4 nanorings as
      anode materials for lithium-ion batteries.
AB  - We rationally designed a facile two-step approach to synthesize ZnMn2O4@G
      composite anode material for lithium-ion batteries (LIBs), involving a template
      free fabrication of ZnMn2O4 nanorings and subsequent coating of graphene sheets.
      Notably, it is the first time that ring-like ZnMn2O4 nanostructure is reported.
      Moreover, our system has been demonstrated to be quite powerful in producing
      ZnMn2O4 nanorings regardless of the types of Zn and Mn-containing metal salts
      reactants. The well-known inside-out Ostwald ripening process is tentatively
      proposed to clarify the formation mechanism of the hollow nanorings. When
      evaluated as anode material for LIBs, the resulting ZnMn2O4@G hybrid displays
      significantly improved lithium-storage performance with high specific capacity,
      good rate capability, and excellent cyclability. After 500 cycles, the ZnMn2O4@G
      hybrid can still deliver a reversible capacity of 958 mAh g-1 at a current
      density of 200 mA g-1, much higher than the theoretical capacity of 784 mAh g-1
      for pure ZnMn2O4. The outstanding electrochemical performance should be
      reasonably ascribed to the synergistic interaction between hollow and porous
      ZnMn2O4 nanorings and the three-dimensional interconnected graphene sheets.

PMID- 28436383
TI  - Influence of point defects and impurities on the dynamical stability of delta
      plutonium.
AB  - We use first-principles calculations to provide direct evidence of the effect of
      aluminum, gallium, iron and uranium on the dynamical stability of delta
      plutonium. We first show that the delta phase is dynamically unstable at low
      temperature, as seen in experiments, and that this stability directly depends on
      the plutonium 5f orbital occupancies. Then, we demonstrate that both aluminum and
      gallium stabilize the delta phase, contrary to iron. As for uranium, which is
      created during self-irradiation and whose effect on plutonium has yet to be
      understood, we show that it leaves a few unstable vibrational modes and that
      higher concentrations lead to an almost complete stabilization. Finally, we
      provide an attempt at a consistent analysis of the experimental Pu-Ga phonon
      density of states. We show that the presence of gallium can reproduce only
      partially the experimental measurements, and we investigate how point defects,
      such as interstitials and vacancies, affect the calculated phonon density of
      states.

PMID- 28436384
TI  - Dynamical electrical conductivity of graphene.
AB  - For graphene (a Dirac material) it has been theoretically predicted and
      experimentally observed that DC resistivity is proportional to T 4 when the
      temperature is much less than Bloch-Gruneisen temperature ([Formula: see text])
      and T-linear in the opposite case ([Formula: see text]). Going beyond this case,
      we investigate the dynamical electrical conductivity in graphene using the
      powerful method of the memory function formalism. In the zero frequency regime,
      we obtain the above mentioned behavior which was previously obtained using the
      Bloch-Boltzmann kinetic equation. In the finite frequency regime, we obtain
      several new results: (1) the generalized Drude scattering rate, in the zero
      temperature limit, shows [Formula: see text] behavior at low frequencies
      ([Formula: see text]) and saturates at higher frequencies. We also observed the
      Holstein mechanism, however, with different power laws from that in the case of
      metals; (2) at higher frequencies, [Formula: see text], and higher temperatures
      [Formula: see text], we observed that the generalized Drude scattering rate is
      linear in temperature. In addition, several other results are also obtained. With
      the experimental advancement of this field, these results should be
      experimentally tested.

PMID- 28436385
TI  - Structural and magnetic properties of spin-$1/2$ dimer compound
      Cu$_2$(IPA)$_2$(DMF)(H$_2$O) with a large spin gap.
AB  - We present the synthesis and a detailed investigation of structural and magnetic
      properties of metal-organic compound Cu$_2$(IPA)$_2$(DMF)(H$_2$O) by means of x
      ray diffraction, magnetization, and heat capacity measurements. Single crystals
      of the title compound were synthesized by judicious selection of organic ligand
      and employing a selective hydrothermal reaction route. It crystallizes in an
      orthorhombic structure with space group $Cmca$. The structural analysis revealed
      that two Cu$^{2+}$ ions are held together by the organic component (-O-C-O-) in a
      square paddle-wheel to form spin dimers which are aligned perpendicular to each
      other and are further coupled through organic ligands (isophthalic acid) forming
      two-dimensional layers. Temperature dependent magnetic susceptibility $?chi(T)$
      could be described well using spin-$1/2$ dimer model. The spin susceptibility
      $?chi_{?rm spin} (T)$ shows an exponential decrease in the low temperature
      region, below the broad maximum, confirming the singlet ground state with a large
      spin gap of $?Delta/k_{?rm B} ?simeq 409$~K. The heat capacity $C_{?rm p}$
      measured as a function of temperature also confirms the absence of magnetic long
      range-order down to 2~K.

PMID- 28436386
TI  - Lasting relief of chronic anterior knee pain in young adult after ten weekly
      inductive physiotherapy sessions: A case report.
AB  - BACKGROUND: Patellofemoral pain syndrome particularly impairs quality of life in
      young, physically active subjects. The exact etiology remains unknown, and so
      this syndrome is a challenging condition to treat. Some patients continue to
      experience pain and dysfunction after receiving one or more guidelines-compliant
      conservative treatments. Reducing the likelihood of patellofemoral pain syndrome
      is an important way of preventing the onset of debilitating anterior knee pain at
      all ages of life. CASE: A 24-year-old sportswoman with a 15-month history of
      anterior knee pain and failure of previous guidelines-compliant treatments. We
      treated this patient with techniques derived from the paradigm of inductive
      physiotherapy, in which tone disorders with a central origin may contribute to
      musculoskeletal disorders. One distinctive feature of inductive physiotherapy
      relates to the fact that the painful area is not manipulated directly. RESULTS:
      The effects of physiotherapy were evaluated after ten weekly sessions and then 15
      months later. The changes in the visual analogue pain scale score and the Knee
      Lequesne Index were clinically significant. We also observed an unexpected
      reduction in the static varus misalignment. CONCLUSION: This case could pave the
      way to an innovative neurological approach to the management of patellofemoral
      pain syndrome in the young adult.

PMID- 28436387
TI  - Predictive value of microRNA-143 in evaluating the prognosis of patients with
      hepatocellular carcinoma.
AB  - OBJECTIVE: The study aims to evaluate the predictive value of microRNA-143 (miR
      143) for the prognosis of patients with hepatocellular carcinoma (HCC). METHODS:
      Between October 2010 and October 2012, 131 HCC patients were selected as a case
      group; meanwhile, 122 healthy controls were enrolled as a control group. The miR
      143 expression in serum was detected by quantitative real-time polymerase chain
      reaction (qRT-PCR). These HCC patients were divided into the high miR-143
      expression group and the low miR-143 expression group based on the threshold of
      receiver operating characteristic (ROC) curve. Kaplan-Meier method was applied to
      analyze the prognosis of HCC patients. RESULTS: MiR-143 exhibited decreased
      expression in the case group significantly compared to the control group. The
      areas under the ROC curve (AUC), sensitivity value and specificity value of the
      miR-143 expression for the diagnosis of HCC were 0.831, 80.30% and 82.40%,
      respectively. The miR-143 expression was negatively correlated with vascular
      invasion, TNM staging, tumor recurrence, metastasis and survival of HCC patients.
      CONCLUSIONS: Our study provides evidence that miR-143 may be negatively
      correlated with the prognosis of HCC and provides a promising strategy for HCC
      treatment and prognosis improvement.

PMID- 28436389
TI  - Ethical Considerations for Deep Brain Stimulation Trials in Patients with Early
      Onset Alzheimer's Disease.
AB  - Several studies of deep brain stimulation (DBS) of the fornix or the nucleus
      basalis of Meynert have been recently conducted in people with Alzheimer's
      disease, with several recruiting participants <65 and thus have early-onset
      Alzheimer's disease (EOAD). Although EOAD accounts for less than 5.5% of AD
      cases, ethical considerations must still be made when performing DBS trials
      including these participants since a portion of people with EOAD, especially
      those possessing autosomal-dominant mutations, have an atypical and more
      aggressive disease progression. These considerations include appropriate patient
      selection and signing of an informed consent for genetic testing; appropriate
      study design; potential outcomes that people with EOAD could expect; and accurate
      interpretation and balanced discussion of trial results. Finally, recommendations
      for future DBS for AD trials will be made to ensure that EOAD patients will not
      experience avoidable harms should they be enrolled in these experimental studies.

PMID- 28436388
TI  - Toward the Automation of Diagnostic Conversation Analysis in Patients with Memory
      Complaints.
AB  - BACKGROUND: The early diagnosis of dementia is of great clinical and social
      importance. A recent study using the qualitative methodology of conversation
      analysis (CA) demonstrated that language and communication problems are evident
      during interactions between patients and neurologists, and that interactional
      observations can be used to differentiate between cognitive difficulties due to
      neurodegenerative disorders (ND) or functional memory disorders (FMD). OBJECTIVE:
      This study explores whether the differential diagnostic analysis of doctor
      patient interactions in a memory clinic can be automated. METHODS: Verbatim
      transcripts of conversations between neurologists and patients initially
      presenting with memory problems to a specialist clinic were produced manually (15
      with FMD, and 15 with ND). A range of automatically detectable features focusing
      on acoustic, lexical, semantic, and visual information contained in the
      transcripts were defined aiming to replicate the diagnostic qualitative
      observations. The features were used to train a set of five machine learning
      classifiers to distinguish between ND and FMD. RESULTS: The mean rate of correct
      classification between ND and FMD was 93% ranging from 97% by the Perceptron
      classifier to 90% by the Random Forest classifier.Using only the ten best
      features, the mean correct classification score increased to 95%. CONCLUSION:
      This pilot study provides proof-of-principle that a machine learning approach to
      analyzing transcripts of interactions between neurologists and patients
      describing memory problems can distinguish people with neurodegenerative dementia
      from people with FMD.

PMID- 28436390
TI  - Biomarkers for Early Diagnosis of Alzheimer's Disease in the Oldest Old: Yes or
      No?
AB  - In recent years, many efforts have been spent to identify sensitive biomarkers
      able to improve the accuracy of Alzheimer's disease (AD) diagnosis. Two different
      workgroups (NIA-AA and IWG) included cerebrospinal fluid (CSF) and neuroimaging
      findings in their sets of criteria in order to improve diagnostic accuracy as
      well as early diagnosis. The number of subjects with cognitive impairment
      increases with aging but the oldest old (>=85 years of age), the fastest growing
      age group, is still the most unknown from a biological point of view. For this
      reason, the aim of our narrative mini-review is to evaluate the pertinence of the
      new criteria for AD diagnosis in the oldest old. Moreover, since different
      subgroups of oldest old have been described in scientific literature (escapers,
      delayers, survivors), we want to outline the clinical profile of the oldest old
      who could really benefit from the use of biomarkers for early diagnosis.
      Reviewing the literature on biomarkers included in the diagnostic criteria, we
      did not find a high degree of evidence for their use in the oldest old, although
      CSF biomarkers seem to be still the most useful for excluding AD diagnosis in the
      "fit" subgroup of oldest old subjects, due to the high negative predictive value
      maintained in this age group.

PMID- 28436391
TI  - Prediction of Conversion to Alzheimer's Disease with Longitudinal Measures and
      Time-To-Event Data.
AB  - BACKGROUND: Identifying predictors of conversion to Alzheimer's disease (AD) is
      critically important for AD prevention and targeted treatment. OBJECTIVE: To
      compare various clinical and biomarker trajectories for tracking progression and
      predicting conversion from amnestic mild cognitive impairment to probable AD.
      METHODS: Participants were from the ADNI-1 study. We assessed the ability of 33
      longitudinal biomarkers to predict time to AD conversion, accounting for
      demographic and genetic factors. We used joint modelling of longitudinal and
      survival data to examine the association between changes of measures and disease
      progression. We also employed time-dependent receiver operating characteristic
      method to assess the discriminating capability of the measures. RESULTS: 23 of 33
      longitudinal clinical and imaging measures are significant predictors of AD
      conversion beyond demographic and genetic factors. The strong phenotypic and
      biological predictors are in the cognitive domain (ADAS-Cog; RAVLT), functional
      domain (FAQ), and neuroimaging domain (middle temporal gyrus and hippocampal
      volume). The strongest predictor is ADAS-Cog 13 with an increase of one SD in
      ADAS-Cog 13 increased the risk of AD conversion by 2.92 times. CONCLUSION:
      Prediction of AD conversion can be improved by incorporating longitudinal change
      information, in addition to baseline characteristics. Cognitive measures are
      consistently significant and generally stronger predictors than imaging measures.

PMID- 28436392
TI  - The DNA Damage Response in Neurons: Die by Apoptosis or Survive in a Senescence
      Like State?
AB  - Neurons are exposed to high levels of DNA damage from both physiological and
      pathological sources. Neurons are post-mitotic and their loss cannot be easily
      recovered from; to cope with DNA damage a complex pathway called the DNA damage
      response (DDR) has evolved. This recognizes the damage, and through kinases such
      as ataxia-telangiectasia mutated (ATM) recruits and activates downstream factors
      that mediate either apoptosis or survival. This choice between these opposing
      outcomes integrates many inputs primarily through a number of key cross-road
      proteins, including ATM, p53, and p21. Evidence of re-entry into the cell-cycle
      by neurons can be seen in aging and diseases such as Alzheimer's disease. This
      aberrant cell-cycle re-entry is lethal and can lead to the apoptotic death of the
      neuron. Many downstream factors of the DDR promote cell-cycle arrest in response
      to damage and appear to protect neurons from apoptotic death. However, neurons
      surviving with a persistently activated DDR show all the features known from cell
      senescence; including metabolic dysregulation, mitochondrial dysfunction, and the
      hyper-production of pro-oxidant, pro-inflammatory and matrix-remodeling factors.
      These cells, termed senescence-like neurons, can negatively influence the
      extracellular environment and may promote induction of the same phenotype in
      surrounding cells, as well as driving aging and age-related diseases. Recently
      developed interventions targeting the DDR and/or the senescent phenotype in a
      range of non-neuronal tissues are being reviewed as they might become of
      therapeutic interest in neurodegenerative diseases.

PMID- 28436394
TI  - Sarcomere Dysfunction in Nemaline Myopathy.
AB  - Nemaline myopathy (NM) is among the most common non-dystrophic congenital
      myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle
      weakness and the presence of nemaline bodies in the muscle fiber. The clinical
      phenotype of NM patients is quite diverse, ranging from neonatal death to normal
      lifespan with almost normal motor function. As the respiratory muscles are
      involved as well, severely affected patients are ventilator-dependent. The
      mechanisms underlying muscle weakness in NM are currently poorly understood.
      Therefore, no therapeutic treatment is available yet.Eleven implicated genes have
      been identified: ten genes encode proteins that are either components of thin
      filament, or are thought to contribute to stability or turnover of thin filament
      proteins. The thin filament is a major constituent of the sarcomere, the smallest
      contractile unit in muscle. It is at this level of contraction - thin-thick
      filament interaction - where muscle weakness originates in NM patients.This
      review focusses on how sarcomeric gene mutations directly compromise sarcomere
      function in NM. Insight into the contribution of sarcomeric dysfunction to muscle
      weakness in NM, across the genes involved, will direct towards the development of
      targeted therapeutic strategies.

PMID- 28436396
TI  - Femoral tunnel positioning using an anteromedial technique for ACL
      reconstruction: A radiographic study with a cadaveric model.
AB  - BACKGROUND: We studied the anatomic positioning of the femoral tunnel during
      simulated anterior cruciate ligament reconstruction using an anteromedial portal
      approach in cadaveric models. METHODS: In thirty cadaveric human knee specimens,
      simulation of an arthroscopic anterior cruciate ligament reconstruction was
      performed and the femoral tunnel was drilled using an anteromedial portal. A
      Kirschner wire was passed into the tunnel and radiographs were obtained. These
      radiographs were then evaluated in the coronal and sagittal planes. Angles
      between the axis of the femoral tunnel and the joint line in the coronal plane
      (alpha, alpha) or the femoral long axis in the sagittal plane (beta, beta) were
      calculated for each specimen. The external aperture of the femoral tunnel was
      defined as the point of exit of the Kirschner wire from the lateral femoral
      cortex. This was evaluated relative to a prescribed rectangle and coordinate
      axis, with the radiographic quadrant method of Bernard, to assess the accuracy of
      femoral tunnel placement. RESULTS: The mean alpha in the coronal plane was
      48.53?, the mean beta in the sagittal plane was 32.23?. All of the femoral tunnel
      external apertures were located outside of the rectangleCONCLUSION: We evaluated
      the positioning of the femoral tunnel and the external aperture of the femoral
      tunnel with the anteromedial portal technique. This study provides a reference
      standard to assess accurately femoral tunnel positioning on postoperative
      radiographs.

PMID- 28436395
TI  - Phase IIb Study of Intranasal Glutathione in Parkinson's Disease.
AB  - BACKGROUND: Reduced glutathione (GSH) is an endogenously synthesized tripeptide
      depleted early in the course of Parkinson's disease (PD) and GSH augmentation has
      been proposed as a therapeutic strategy in PD. OBJECTIVE: This Phase IIb study
      was designed to evaluate whether a Phase III study of intranasal GSH, (in)GSH,
      for symptomatic relief is warranted and to determine the most appropriate trial
      design for a disease-modification study. METHODS: This was a double-blind,
      placebo-controlled trial of 45 individuals with Hoehn & Yahr Stage 1-3 PD.
      Participants were randomized to receive intranasal placebo (saline), 100 mg GSH,
      or 200 mg GSH thrice daily for three months, and were observed over a one-month
      washout period. RESULTS: All cohorts improved over the intervention period,
      including placebo. The high-dose group demonstrated improvement in total Unified
      PD Rating Scale (UPDRS) (-4.6 (4.7), P = 0.0025) and UPDRS motor subscore (-2.2
      (3.8), P = 0.0485) over baseline, although neither treatment group was superior
      to placebo. One participant in the high-dose GSH cohort developed cardiomyopathy.
      CONCLUSIONS: Although predicted improvements in PD total and motor scores were
      observed, these data do not suggest (in)GSH is superior to placebo after a three
      month intervention. The symptomatic effects are sufficient to warrant a delayed
      start or wash-out design study for disease-modification trials. Whether long-term
      use of (in)GSH leads to clinical improvements that are sustained and
      significantly different than placebo will require appropriately-powered longer
      duration studies in larger cohorts. The improvement in the placebo arm was more
      robust than has been observed in previous PD studies and warrants further
      investigation.

PMID- 28436397
TI  - Reduced culture time and improved isolation rate through culture of sonicate
      fluid in blood culture bottles.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate if the
      cultivation of sonicate fluid (SFC) in blood culture bottles (BCB) leads to a
      higher rate of bacterial isolations than agar plate culture (APC) and to
      investigate whether the utilization of BCB leads to a reduction in culture time.
      METHODS: We performed a retrospective analysis of 206 revision total knee and
      total hip arthroplasty patients comparing the results of both synovial fluid
      culture and SFC in both BCB and conventional APC. RESULTS: The use of BCB
      improved both the rate of positive bacterial isolations and reduced the culture
      time for synovial fluid as well as SFC. Fifty-one patients showed a bacterial
      isolation in SFC-APC and 101 in SFC-BCB. For synovial fluid 24 patients showed a
      bacterial isolation on APC and 37 showed a bacterial isolation in BCB. The
      synovial fluid cultures showed growth on APC after an average of 2.8 days vs. 1.8
      days in BCB. The SFC-APC showed growth after an average of 4.2 days vs. 2.9 days
      for SFC-BCB. CONCLUSIONS: The culture of synovial and sonicate fluid in BCB leads
      to more positive bacterial isolations and quicker bacterial growth than
      conventional agar plate cultures.

PMID- 28436398
TI  - Effects of dose and duration of Robot-Assisted Gait Training on walking ability
      of children affected by cerebral palsy.
AB  - BACKGROUND: Robot-Assisted Gait Training (RAGT) is a widespread approach for
      locomotion rehabilitation but information about intervention frequency and
      duration is still lacking. OBJECTIVE: To evaluate the effect of frequency and
      duration of a RAGT on motor outcome of children affected by Cerebral Palsy (CP).
      METHODS: Forty-four CP children (age 4-17) underwent one among four different
      intensive trainings with equal dose of intervention, combining Task-Oriented
      Physiotherapy (TOP) and RAGT: 40 sessions (4 sessions/week) over 10 weeks of sole
      TOP (group1) or RAGT (group2) or RAGT and TOP (2 + 2 sessions/week; group3); 40
      sessions in shorter period (4 weeks) of RAGT and TOP (5 + 5 sessions/week;
      group4). Each child was assessed before, after the training and after 3 months
      with: Ashworth, gross motor function measure (GMFM)-88, GMFM-66, six minutes
      walking test and gait analysis. RESULTS: No differences among the 4 protocols
      were highlighted although both groups with exclusive physiotherapy and RAGT
      obtained significant improvements in GMFM-88, GMFM-E and GMFM-66 while the mixed
      approaches did not show significant changes. CONCLUSION: Single-treatment
      approaches seem to be more effective than mixed approaches, independently from
      the duration (4 or 10 weeks). RAGT seems to have similar effect with respect to
      the traditional TOP, at least over 10 weeks.

PMID- 28436399
TI  - Identification of patients with preeclampsia from normal subjects using wavelet
      based spectral analysis of heart rate variability.
AB  - BACKGROUND: The spectral analysis of the heart rate variability (HRV) shows a
      decrease in the power of the high frequency (HF) component in preeclamptic
      pregnancy compared with normal pregnancy; such a decrease is associated with an
      increase in the low frequency (LF) and the very low frequency (VLF) power. The
      physiological interpretation is that preeclamptic pregnancy is associated with a
      facilitation of sympathetic regulation and an attenuation of parasympathetic
      influence of HR compared with non-pregnancy and normal pregnancy. OBJECTIVE: To
      use an efficient nased on spectral analysis non-invasive technique to identify
      preeclamptic pregnant subjects from normal pregnant in Oman. METHODS: The soft
      decision wavelet-based technique is implemented to find the power of the HRV
      bands in high resolution manner compared to the classical fast Fourier Transform
      method. Data was obtained from 20 preeclamptic pregnant subjects and 20 normal
      pregnant controls of the same pregnancy duration, obtained from Nizwa and Sultan
      Qaboos University hospitals in Oman. RESULTS: The soft-decision wavelet method
      succeeds to identify patients from normal pregnant with specificity, sensitivity
      and accuracy of 90%, 80% and 85%, respectively, compared to the FFT which results
      in 75% specificity, sensitivity and accuracy. CONCLUSION: The LF power obtained
      by Soft-decision wavelet decomposition is shown to be a successful feature for
      identification of preeclampsia.

PMID- 28436400
TI  - The Vertect Jack Device: A new method for augmentation of vertebral fractures.
      Clinical study with comparisons to kyphoplasty.
AB  - BACKGROUND: Kyphoplasty is a proven minimally invasive procedure for the
      treatment of patients with osteoporotic fractures. By augmentation of fractured
      vertebral body, however, a very large portion of the intervertebral structures
      will be destroyed. With the help of a new device (Vertect Jack Device), the
      erection of the vertebral body will be carried out more gentle. OBJECTIVE: In the
      present study, the new method should be clinically tested for efficacy and safety
      for the first time. As a comparison results of previous treatments with
      kyphoplasty were used. METHODS: For Vertect Jack Device study patients with
      painful vertebral fractures were selected in which conservative treatment had not
      yielded sufficient results. For comparison random data from the records of
      patients who had been treated with kyphoplasty were selected. The Vertect Jack
      Device was placed under the central fractures and then erected. After having
      restorted the vertebral height the device was removed and cement injected.
      Clinical and radiological examinations were carried out before and after 1,3, and
      6 months. RESULTS: In the Vertect Jack Device Group the data of 40 patients were
      evaluated. For group 2 (kyphoplasty) 50 patients were selected. There was a
      significant difference in the duration of the surgery (Group 1: 27.4, Group 2:
      45.9 minutes). A significant difference of 20 mm with regard to the reduction of
      VAS scores (0-100 mm pain intensity) was detected. Under the application of the
      Vertect Jack Device an average increase of 3.1 mm of vertebral height was
      achieved. In group 2, the erection averaged 0.4 mm. A correlation between the
      postoperative change of vertebral body height and VAS scores could not be
      detected in both groups. CONCLUSIONS: The comparative analysis of this study
      shows that promising results can be achieved with the augmentation of vertebral
      fractures with the Vertect Jack Device. When compared with kyphoplasty,
      advantages show in terms of targeted and thus more gentle application possibility
      and better pain relief over a period of 6 months after surgery. Further study
      results should help to demonstrate the efficacy and tolerability of the new
      method.

PMID- 28436401
TI  - Effects of amplitude and phase-duration modification on electrically induced
      contraction force and discomfort.
AB  - BACKGROUND: Neuromuscular electrical stimulation (NMES) is commonly used in
      rehabilitation. However, the optimal combination of phase-duration and amplitude
      for enhancing motor output is not yet resolved. OBJECTIVE: To test the effects of
      increasing phase-duration and amplitude on isometric knee extension force and
      discomfort, while controlling the effects of electrode-skin resistance and body
      mass index (BMI). METHODS: Twenty-one healthy volunteers participated in the
      study. Stimulation was set at 250 MUsec phase-duration and 45 Hz to evoke 10% of
      maximal voluntary isometric contraction of the quadriceps. Electrode-skin
      resistance was measured. Then, electrically induced contraction (EIC) forces and
      discomfort level were measured under four conditions: Moderate (25%) or
      substantial increase (50%) from baseline amplitude with constant phase-duration
      and moderate (25%) or substantial increase (50%) in phase-duration with amplitude
      constant. RESULTS: Compared with baseline, EIC force was significantly higher in
      all intensification conditions, while discomfort was significantly greater in all
      conditions except for moderate increase in phase-duration (p= 0.44). Amplitude
      intensification produced significantly higher force and greater discomfort than
      phase-duration. Electrode-skin resistance and BMI were not significant
      covariates. CONCLUSIONS: Greater force is elicited by increasing amplitude than
      by similar increase in phase-duration; however, the associated discomfort is also
      higher. Clinicians may use phase-duration while conditioning for NMES.

PMID- 28436402
TI  - Anterior fracture dislocation of the sacroiliac joint: A case report and
      literature review.
AB  - Publications describing the diagnosis and treatment of anterior dislocation of
      the sacroiliac joint are scarce. We report the case a 19-year-old female at 8
      weeks' gestation who presented with anterior fracture dislocation of the right
      sacroiliac joint, posterior fracture dislocation of the left sacroiliac joint
      (crescent fracture), and incomplete abortion resulting from high energy trauma.
      Orthopedic surgery involved standard anterior sacroiliac joint plating using an
      ilioinguinal approach combined with a modified Stoppa approach. Three attempts at
      complete abortion failed. Complete abortion was eventually achieved by dilatation
      and curettage two weeks after orthopedic surgery. Our findings reveal a need to
      improve techniques for diagnosis and treatment of anterior fracture dislocation
      of the sacroiliac joint, so greater attention can be paid to the rapid and
      effective management of associated comorbidities, and those resulting from the
      initial trauma.

PMID- 28436403
TI  - Novel bioprinting method using a pectin based bioink.
AB  - One major challenge of bioprinting is to develop a viable bioink to act as an
      extracellular matrix. This study investigated a novel method for bioprinting
      using a pectin based bioink. Besides pectin, Pluronic(r) F-127 was incorporated
      into the bioink to obtain the desired shape during the initial bioprinting
      process at 37?C. Once an object was printed it was treated with Ca2+ (pectin
      cross-linker) to create the final tissue/organ structure. The results indicated
      that pectin/Pluronic(r) F-127 is a potential bioink. Moreover, this methodology
      provides a novel and fast approach for bioprinting.

PMID- 28436404
TI  - On the estimation of maximum stress in cushions for wheelchair patients who are
      prone to develop pressure injuries.
AB  - BACKGROUND: Pressure injuries are an important health care issue. This problem is
      even more evident with patients with neurological conditions. OBJECTIVE: This
      study aims to develop an analytical tool to predict the magnitude of the maximum
      stresses developed at the wheelchair cushion-patient contact area. METHOD:
      Newton's polynomial interpolation method was applied in order to obtain
      correlations between the maximum stress developed and the weight of the patient
      and the maximum pressure and body mass index (BMI) of the participants. For this
      study it was recruited five able-bodies and nine patients with spinal cord
      injury. RESULTS: The agreement between the computed stress values and those
      measured with the able-bodied group is excellent, but in the patients within the
      spinal cord injury group, the concordance is poor. The correlations were applied
      in data from Crawford's study, and predictions of pressures show lack of
      agreement. CONCLUSIONS: Correlation between the weight of a person and the
      maximum stress developed by him or her while sitting for extended periods of time
      has been demonstrated. The lack of agreement between estimated and measured
      values in spinal cord injuries and Crawford's data can be mainly attributed to
      some sort of neurological status.

PMID- 28436405
TI  - A comparison of methods for three-class mammograms classification.
AB  - BACKGROUND: Mammography is considered the gold standard for early breast cancer
      detection but it is very difficult to interpret mammograms for many reason.
      Computer aided diagnosis (CAD) is an important development that may help to
      improve the performance in breast cancer detection. OBJECTIVE: We present a CAD
      system based on feature extraction techniques for detecting abnormal patterns in
      digital mammograms. METHODS: Computed features based on gray-level co-occurrence
      matrices (GLCM) are used to evaluate the effectiveness of textural information
      possessed by mass regions. A total of 20 texture features are extracted from each
      mammogram. The ability of feature set in differentiating normal, benign and
      malign tissue is investigated using a Support Vector Machine (SVM) classifier,
      Naive Bayes classifier and K-Nearest Neighbor (k-NN) classifier. The efficiency
      of classification is provided using cross-validation technique. Support Vector
      Machine was originally designed for binary classification. We constructed a three
      class SVM classifier by combining two binary classifiers and then compared his
      performance with classifiers intended for multi-class classification. To evaluate
      the classification performance, confusion matrix and Receiver Operating
      Characteristic (ROC) analysis were performed. RESULTS: Obtained results indicate
      that SVM classification results are better than the k-NN and Naive Bayes
      classification results, with accuracy ratio of 65% according to 51.6% and 38.1%,
      respectively.The unbalanced classification that occurs in all three
      classification tests is reason for unsatisfactory accuracy. CONCLUSIONS: Obtained
      experimental results indicate that the proposed three-class SVM classifier is
      more suitable for practical use than the other two methods.

PMID- 28436406
TI  - Questionnaire-based evaluation of mobile phone interference with medical
      electrical equipment in Swedish hospitals.
AB  - National recommendations in Sweden recommend a safety distance of 3 meter (m)
      between mobile phones and medical-electrical (ME) equipment in hospitals. A
      questionnaire was used to investigate how often mobile phones were reported to
      interfere with ME products in clinical practice across Sweden. The results
      confirmed that ME equipment can be affected by mobile phone use but, the risk of
      the patient's outcome being affected were minimal; no cases were identified which
      led to injury or death. In conclusion, the results support recommendations for a
      general safety distance of 0.5 m between mobile phones and ME equipment in care
      environments.

PMID- 28436407
TI  - Design of a pulsatile DC electromagnetic blood pump for ECMO.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has developed rapidly and
      becomes a significant treatment for emergency. Current blood pumps for ECMO have
      different disadvantages. OBJECTIVE: To design a pulsatile DC electromagnetic
      blood pump for ECMO. METHODS: The design is presented with a driving principle
      which the rectilinear reciprocation of a magnet inside energized solenoids is
      implemented, and with a structure of solenoids with compensation coils.
      Furthermore, a prototype was constructed and the performance indexes of it were
      measured with the experimental evaluations, where the acceleration experiment was
      performed without any loads, and the flows were measured in the ranges of preload
      and afterload are 5 to 30 mmHg and 50 to 80 mmHg respectively when the frequency
      of the motion is 80 beats per minute. RESULTS: The electromagnetic force is
      greater than 1.4 N when the DC reaches 2.7 A and the flow of the prototype is
      greater than 3.0 L/min except the differences between the preload and the
      afterload are greater than or equal to 70 mmHg. CONCLUSIONS: The design of the
      blood pump for ECMO meets the theoretical and clinical requirements.

PMID- 28436408
TI  - Design of a smart ECG garment based on conductive textile electrode and flexible
      printed circuit board.
AB  - A smart electrocardiogram (ECG) garment system was designed for continuous, non
      invasive and comfortable ECG monitoring, which mainly consists of four
      components: Conductive textile electrode, garment, flexible printed circuit board
      (FPCB)-based ECG processing module and android application program. Conductive
      textile electrode and FPCB-based ECG processing module (6.8 g, 55 mm * 53 mm * 5
      mm) are identified as two key techniques to improve the system's comfort and
      flexibility. Preliminary experimental results verified that the textile
      electrodes with circle shape, 40 mm size in diameter, and 5 mm thickness sponge
      are best suited for the long-term ECG monitoring application. The tests on the
      whole system confirmed that the designed smart garment can obtain long-term ECG
      recordings with high signal quality.

PMID- 28436409
TI  - Assessment of women's attitude to and perception of transvaginal sonography in
      Nigeria.
AB  - PURPOSE: To assess the attitude to and perception of transvaginal sonography
      (TVS) among Nigerian women of mixed educational status in order to ascertain
      factors that may prevent them from submitting to TVS when recommended. METHODS: A
      Cross-sectional survey was adopted for the study. Subjects were enrolled from one
      missionary, one government and eight private hospitals. The instruments for data
      collection were visual analogue scale (VAS), to ascertain patients'
      pain/discomfort experience, and a researcher-developed semi-structured
      questionnaire. The level of pain/discomfort on the VAS was categorized into four
      on a scale of 100. The categories were: 0-5 (no pain), 6-40 (mild pain), 41-74
      (moderate pain), and 75-100 (severe pain). RESULTS: The majority (50.6%) of the
      respondents who attained secondary education had positive attitude to TVS. The
      majority majority of the respondents (63.1%) preferred female sonographers. A
      majority of the respondents (54.1%) perceived TVS as not embarrassing, 78% did
      not consider it stressful, 96.9% reported that the sonographers were
      professional, 46.7% felt that a chaperon was needed, 98.4% reported there was
      enough privacy and 84.7% reported they needed prior information. Most of the
      respondents (82%) were willing to consent to TVS in future, 90.5% reported no
      pain, 8.6% reported mild pain/discomfort and 0.9% reported moderate pain.
      CONCLUSIONS: Majority of our respondents had a positive attitude to TVS and were
      willing to consent to TVS in future, hence it was acceptable to them. It was
      however observed that acceptability increased with increasing education.

PMID- 28436410
TI  - A new approach to develop computer-aided diagnosis scheme of breast mass
      classification using deep learning technology.
AB  - PURPOSE: To develop and test a deep learning based computer-aided diagnosis (CAD)
      scheme of mammograms for classifying between malignant and benign masses.
      METHODS: An image dataset involving 560 regions of interest (ROIs) extracted from
      digital mammograms was used. After down-sampling each ROI from 512*512 to 64*64
      pixel size, we applied an 8 layer deep learning network that involves 3 pairs of
      convolution-max-pooling layers for automatic feature extraction and a multiple
      layer perceptron (MLP) classifier for feature categorization to process ROIs. The
      3 pairs of convolution layers contain 20, 10, and 5 feature maps, respectively.
      Each convolution layer is connected with a max-pooling layer to improve the
      feature robustness. The output of the sixth layer is fully connected with a MLP
      classifier, which is composed of one hidden layer and one logistic regression
      layer. The network then generates a classification score to predict the
      likelihood of ROI depicting a malignant mass. A four-fold cross validation method
      was applied to train and test this deep learning network. RESULTS: The results
      revealed that this CAD scheme yields an area under the receiver operation
      characteristic curve (AUC) of 0.696+/-0.044, 0.802+/-0.037, 0.836+/-0.036, and
      0.822+/-0.035 for fold 1 to 4 testing datasets, respectively. The overall AUC of
      the entire dataset is 0.790+/-0.019. CONCLUSIONS: This study demonstrates the
      feasibility of applying a deep learning based CAD scheme to classify between
      malignant and benign breast masses without a lesion segmentation, image feature
      computation and selection process.

PMID- 28436411
TI  - Benign mixed epithelial and stromal tumor of the kidney with inferior vena cava
      tumor thrombus: A rare case report and review of literature.
AB  - Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare renal tumor
      composed of epithelial and stromal cells. In this study, we report a rare case of
      MESTK, which was pathologically benign but complicated with renal vein and
      inferior vena cava tumor thrombus. The 50-year-old female patient was admitted to
      hospital for a mass on the left kidney. Computed tomography showed a 32 mm*18 mm
      mass with slight delayed enhancement in the left renal sinus, and neoplastic
      thrombus was detected in left renal vein and inferior vena cava. A preoperative
      diagnosis of renal leiomyoma was made by needle biopsy and a laparoscopic radical
      nephrectomy with thrombectomy was performed. Histologically, the tumor and
      thrombus were composed of proliferative spindle cells and a small amount of
      tubular structures. Both kinds of the cells were well differentiated with no
      atypia or mitosis of nuclei. Immunohistochemical staining showed positive for CK,
      Ki-67 in the tubular cells and desmin, actin, estrogen receptors, progesterone
      receptors in the spindle cells. Finally, the diagnosis of MESTK was established.
      No recurrence or metastasis was found in the patient with a followed-up period of
      12 months after the surgery. Due to the difficulty in diagnosis of MESTK,
      documentation with more cases of MESTK is needed to further understand its
      pathogenesis, biological behavior, preoperative diagnosis and optimal management
      of patient treatment.

PMID- 28436413
TI  - Multimodal diagnosis of caseous calcification of the mitral annulus in a patient
      with suspected left ventricular tumor.

PMID- 28436412
TI  - Subinguinal microsurgical varicocelectomy with intraoperative microvascular
      Doppler ultrasound leads to the pain-free outcome after surgery.
AB  - OBJECTIVE: To determine efficacy of intraoperative microvascular Doppler
      ultrasound in assisting subinguinal microsurgical varicocelectomy for pain relief
      in the treatment of painful varicoceles, compared to the microsurgery without
      Doppler ultrasound. METHODS: Total 153 patients underwent microsurgical
      varicocelectomy were randomly allocated to two groups: Groups 1 and 2 included 82
      and 71 patients monitored with and without using intraoperative microvascular
      Doppler ultrasound, respectively. The assessments were compared between two
      groups, including intraoperative parameters (vessel numbers and operative time)
      and postoperative outcomes (pain resolution, complications and recurrence).
      RESULTS: The average numbers of internal spermatic veins ligated (13.87+/-6.43 vs
      11.72+/-5.66) and arteries preserved (1.96+/-0.87 vs 1.73+/-0.86) were
      significantly greater in Group 1 with Doppler ultrasound. Precisely, the smaller
      size of the internal spermatic veins was ligated and the more encircled arteries
      were also preserved in Group 1. In two groups with and without using Doppler
      ultrasound, 56 (68.3%) and 36 (50.7%) patients experienced a complete resolution
      of pain, 21 (25.6%) and 29 (40.9%) patients experienced partial resolution,
      whereas 5 (6.1%) and 6 (8.5%) patients experienced no change in the chronic pain,
      respectively. Thus, patients in Group 1 had a better outcome in chronic pain
      resolution (P = 0.033). The operative time, complications and recurrence rate
      were not different between the two groups. CONCLUSIONS: Subinguinal microsurgical
      varicocelectomy is an effective method to treat painful varicoceles. With the
      assistance of Doppler Ultrasound monitoring, greater numbers of vessels were
      identified and a better outcome of pain resolution was achieved.

PMID- 28436414
TI  - Daily diet containing canned products significantly increases serum
      concentrations of endocrine disruptor bisphenol A in young women.

PMID- 28436415
TI  - Blood pressure reduction in patients with accessory renal arteries and bilateral
      single renal arteries after catheter-based renal denervation: a prospective study
      with 3-year follow-up.
AB  - INTRODUCTION: Catheter-based renal denervation (RD) is an effective treatment
      leading to a significant reduction of systolic and diastolic blood pressure (BP)
      in patients with resistant hypertension. OBJECTIVES: The aim of this prospective
      study was to assess the BP-lowering and pulse pressure (PP)- lowering effects in
      patients with accessory and bilateral single renal arteries after catheter-based
      RD during a 3-year follow-up. PATIENTS AND METHODS: The study included 31
      patients with diagnosed resistant hypertension. Patients were classified into 2
      groups: group 1 included patients with accessory renal arteries, and group 2,
      with bilateral single renal arteries. The BP and PP reduction levels were
      measured before the procedure and at 6, 12, 24, and 36 months after the
      procedure. RESULTS: All procedures were successful. In group 1, mean systolic BP,
      diastolic BP, and PP at baseline were 172.7 mm Hg, 98.9 mm Hg, and 74.4 mm Hg,
      respectively. Systolic BP, diastolic BP, and PP reduction levels were,
      respectively, -26.9, 19.2, and 7.5 at 6 months; -33.3, 16.1, and 16.4 at 12
      months; -29.2, 14, and 18.2 at 24 months; and -28.6, 13.6, and 13.7 at 36 months.
      In group 2, mean systolic BP, diastolic BP, and PP at baseline were 175.6 mm Hg,
      100.1 mm Hg, and 75.5 mm Hg, respectively. Systolic BP, diastolic BP, and PP
      reduction levels were, respectively, -26, 10.5, and 15.5 at 6 months; -22, 8.9,
      and 13 at 12 months; -28, 12.4, and 15.6 at 24 months; and -24.6, 14.97, and 9.2
      at 36 months. Significant reductions were observed for systolic BP in group 1 and
      for PP and systolic and diastolic BP in group 2. CONCLUSIONS: RD successfully
      reduced systolic BP in patients with resistant hypertension and accessory renal
      arteries. PP reduction after RD in patients with accessory renal arteries was
      less pronounced than in patients with bilateral single renal arteries.

PMID- 28436417
TI  - Energy scaling of targeted optimal control of complex networks.
AB  - Recently it has been shown that the control energy required to control a
      dynamical complex network is prohibitively large when there are only a few
      control inputs. Most methods to reduce the control energy have focused on where,
      in the network, to place additional control inputs. Here, in contrast, we show
      that by controlling the states of a subset of the nodes of a network, rather than
      the state of every node, while holding the number of control signals constant,
      the required energy to control a portion of the network can be reduced
      substantially. The energy requirements exponentially decay with the number of
      target nodes, suggesting that large networks can be controlled by a relatively
      small number of inputs as long as the target set is appropriately sized. We
      validate our conclusions in model and real networks to arrive at an energy
      scaling law to better design control objectives regardless of system size, energy
      restrictions, state restrictions, input node choices and target node choices.

PMID- 28436416
TI  - LPP is a Src substrate required for invadopodia formation and efficient breast
      cancer lung metastasis.
AB  - We have previously shown that lipoma preferred partner (LPP) mediates TGFbeta
      induced breast cancer cell migration and invasion. Herein, we demonstrate that
      diminished LPP expression reduces circulating tumour cell numbers, impairs cancer
      cell extravasation and diminishes lung metastasis. LPP localizes to invadopodia,
      along with Tks5/actin, at sites of matrix degradation and at the tips of
      extravasating breast cancer cells as revealed by intravital imaging of the chick
      chorioallantoic membrane (CAM). Invadopodia formation, breast cancer cell
      extravasation and metastasis require an intact LPP LIM domain and the ability of
      LPP to interact with alpha-actinin. Finally, we show that Src-mediated LPP
      phosphorylation at specific tyrosine residues (Y245/301/302) is critical for
      invadopodia formation, breast cancer cell invasion and metastasis. Together,
      these data define a previously unknown function for LPP in the formation of
      invadopodia and reveal a requirement for LPP in mediating the metastatic ability
      of breast cancer cells.

PMID- 28436418
TI  - Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by
      Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2.
AB  - Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1-3 have been
      synthesized and fully characterized. 1-3 have similar mononuclear structures with
      the metal and ligand ratio of 1:2. 1-3 exhibited higher cytotoxicity than the OD
      ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80-3 and SK-OV-3/DDP
      cells, with IC50 value of 0.23-4.31 MUM. Interestingly, 0.5 MUM 1-3 significantly
      caused HepG2 arrest at S-phase, which was associated with the up-regulation of
      p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A,
      PCNA proteins. In addition, 1-3 induced HepG2 apoptosis via a caspase-dependent
      mitochondrion pathway as evidenced by p53 activation, ROS production, Bax up
      regulation and Bcl-2 down-regulation, mitochondrial dysfunction, cytochrome c
      release, caspase activation and PARP cleavage. Furthermore, 3 inhibited tumor
      growth in HepG2 xenograft model, and displayed more safety profile in vivo than
      cisplatin.

PMID- 28436419
TI  - Nontuberculous mycobacteria in gastrostomy fed patients with cystic fibrosis.
AB  - Multi-drug resistant Mycobacterium abscessus complex (MABSC) is a form of
      Nontuberculous mycobacteria (NTM) of special, international concern in Cystic
      Fibrosis (CF). We hypothesised that gastric juice and percutaneous endoscopic
      gastrostomy (PEG) feeding devices might yield MABSC isolates. Gastric juice and
      sputa from sixteen adult PEG fed CF patients and five replaced PEG tubes were
      studied. Bacterial and fungal isolates were cultured. Mycobacterium were
      identified by rpoB, sodA and hsp65 gene sequencing and strain typed using
      variable number tandem repeat. Bacteria and/or fungi grew from all gastric juice,
      sputa and PEG samples. MABSC were detected in 7 patients. Five had MABSC in their
      sputum. Two had an identical MABSC strain in their sputum and gastric juice and
      one had the same strain isolated from their PEG tube and sputum. Two patients who
      were sputum sample negative had MABSC isolated in their gastric juice or PEG
      tube. MABSC were therefore identified for the first time from a gastric sample in
      a minority of patients. We conclude that gastric juice and PEG-tubes may be a
      potential source of MABSC isolates in CF patients, and these findings warrant
      further study.

PMID- 28436420
TI  - Key role of 15-LO/15-HETE in angiogenesis and functional recovery in later stages
      of post-stroke mice.
AB  - This study sought to clarify the effects of 15-lipoxygenase/15
      hydroxyeicosatetraenoic acid in angiogenesis and neurological functional recovery
      after cerebral ischaemic stroke in mice. In vivo, we performed behavioural tests
      to determine functional recovery after stroke. Double immunofluorescence staining
      of CD31 and Ki67/PCNA was performed to evaluate the effects of 15-lipoxygenase/15
      hydroxyeicosatetraenoic acid on angiogenesis in an MCAO mouse model. In vitro, we
      investigated the effects of 15-hydroxyeicosatetraenoic acid on BMVEC
      proliferation and migration. Our results show that MCAO upregulates 15
      lipoxygenase expression in a time-dependent manner, especially in later stages of
      post-stroke. We confirmed that cerebral infarct area was reduced and neurological
      dysfunction was gradually attenuated after stroke, while 12/15-lipoxygenase
      knockout mice exhibited the opposite effects. Furthermore, immunofluorescence
      studies revealed 15-lipoxygenase increased the proliferation of mouse brain
      vascular endothelial cells in a time-dependent manner, while 12/15-lipoxygenase
      knockout blocked these effects. Moreover, 15-hydroxyeicosatetraenoic acid
      promoted proliferation and tube formation in BMVECs. These results demonstrate
      positive influence of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in
      angiogenesis and neuronal recovery after ischaemic stroke in mice. We also
      confirmed the PI3K/Akt signalling pathway was necessary for the effects of 15
      hydroxyeicosatetraenoic acid in regulation of BMVEC proliferation and migration,
      which may potentially be a novel target for the recovery from ischaemic stroke.

PMID- 28436421
TI  - Abnormal gas-liquid-solid phase transition behaviour of water observed with in
      situ environmental SEM.
AB  - Gas-liquid-solid phase transition behaviour of water is studied with
      environmental scanning electron microscopy for the first time. Abnormal phenomena
      are observed. At a fixed pressure of 450 Pa, with the temperature set to -7 
      degrees C, direct desublimation happens, and ice grows continuously along the
      substrate surface. At 550 Pa, although ice is the stable phase according to the
      phase diagram, metastable liquid droplets first nucleate and grow to ~100-200 MUm
      sizes. Ice crystals nucleate within the large sized droplets, grow up and fill up
      the droplets. Later, the ice crystals grow continuously through desublimation. At
      600 Pa, the metastable liquid grows quickly, with some ice nuclei floating in it,
      and the liquid-solid coexistence state exists for a long time. By lowering the
      vapour pressure and/or increasing the substrate temperature, ice sublimates into
      vapour phase, and especially, the remaining ice forms a porous structure due to
      preferential sublimation in the concave regions, which can be explained with
      surface tension effect. Interestingly, although it should be forbidden for ice to
      transform into liquid phase when the temperature is well below 0  degrees C,
      liquid like droplets form during the ice sublimation process, which is attributed
      to the surface tension effect and the quasiliquid layers.

PMID- 28436422
TI  - Rational design of non-resistant targeted cancer therapies.
AB  - Drug resistance is one of the major problems in targeted cancer therapy. A major
      cause of resistance is changes in the amino acids that form the drug-target
      binding site. Despite of the numerous efforts made to individually understand and
      overcome these mutations, there is a lack of comprehensive analysis of the
      mutational landscape that can prospectively estimate drug-resistance mutations.
      Here we describe and computationally validate a framework that combines the
      cancer-specific likelihood with the resistance impact to enable the detection of
      single point mutations with the highest chance to be responsible of resistance to
      a particular targeted cancer therapy. Moreover, for these treatment-threatening
      mutations, the model proposes alternative therapies overcoming the resistance. We
      exemplified the applicability of the model using EGFR-gefitinib treatment for
      Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Cancer (LSCC) and the ERK2
      VTX11e treatment for melanoma and colorectal cancer. Our model correctly
      identified the phenotype known resistance mutations, including the classic EGFR
      T790M and the ERK2-P58L/S/T mutations. Moreover, the model predicted new
      previously undescribed mutations as potentially responsible of drug resistance.
      Finally, we provided a map of the predicted sensitivity of alternative ERK2 and
      EGFR inhibitors, with a particular highlight of two molecules with a low
      predicted resistance impact.

PMID- 28436423
TI  - A feasible strategy to balance the crystallinity and specific surface area of
      metal oxide nanocrystals.
AB  - Practical, efficient synthesis of metal oxide nanocrystals with good
      crystallinity and high specific surface area by a modified polymer-network gel
      method is demonstrated, taking ZnO nanocrystals as an example. A novel stepwise
      heat treatment yields significant improvement in crystal quality. Such nanophase
      materials can effectively degrade common organic dyes under solar radiation and
      can perform very well in photo-assisted detection of NO2 gas. Other typical metal
      oxide nanocrystals with good crystallinity and high specific surface area were
      also synthesized successfully under similar conditions. This work provides a
      general strategy for the synthesis of metal oxide nanocrystals, balancing the
      crystallinity and specific surface area.

PMID- 28436426
TI  - Stretchable Ag electrodes with mechanically tunable optical transmittance on wavy
      patterned PDMS substrates.
AB  - We report on semi-transparent stretchable Ag films coated on a wavy-patterned
      polydimethylsiloxane (PDMS) substrate for use as stretchable electrodes for
      stretchable and transparent electronics. To improve the mechanical stretchability
      of the Ag films, we optimized the wavy-pattern of the PDMS substrate as a
      function of UV-ozone treatment time and pre-strain of the PDMS substrate. In
      addition, we investigated the effect of the Ag thickness on the mechanical
      stretchability of the Ag electrode formed on the wavy-patterned PDMS substrate.
      The semi-transparent Ag films formed on the wavy-patterned PDMS substrate showed
      better stretchability (strain 20%) than the Ag films formed on a flat PDMS
      substrate because the wavy pattern effectively relieved strain. In addition, the
      optical transmittance of the Ag electrode on the wavy-patterned PDMS substrate
      was tunable based on the degree of stretching for the PDMS substrate. In
      particular, it was found that the wavy-patterned PDMS with a smooth buckling was
      beneficial for a precise patterning of Ag interconnectors. Furthermore, we
      demonstrated the feasibility of semi-transparent Ag films on wavy-patterned PDMS
      as stretchable electrodes for the stretchable electronics based on bending tests,
      hysteresis tests, and dynamic fatigue tests.

PMID- 28436424
TI  - The immunopathology of sepsis and potential therapeutic targets.
AB  - Sepsis is defined as a life-threatening organ dysfunction that is caused by a
      dysregulated host response to infection. In sepsis, the immune response that is
      initiated by an invading pathogen fails to return to homeostasis, thus
      culminating in a pathological syndrome that is characterized by sustained
      excessive inflammation and immune suppression. Our understanding of the key
      mechanisms involved in the pathogenesis of sepsis has increased tremendously, yet
      this still needs to be translated into novel targeted therapeutic strategies.
      Pivotal for the clinical development of new sepsis therapies is the selection of
      patients on the basis of biomarkers and/or functional defects that provide
      specific insights into the expression or activity of the therapeutic target.

PMID- 28436427
TI  - Broad and potent cross clade neutralizing antibodies with multiple specificities
      in the plasma of HIV-1 subtype C infected individuals.
AB  - Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential
      therapeutic tools and leads for the design of a vaccine that can protect human
      beings against various clades of Human Immunodeficiency Virus (HIV). In the
      present study, we screened plasma of 88 HIV-1 infected ART naive individuals for
      their neutralization potential using a standard panel of 18 pseudoviruses
      belonging to different subtypes and different levels of neutralization. We
      identified 12 samples with good breadth of neutralization (neutralized >90% of
      the viruses). Four of these samples neutralized even the difficult-to-neutralize
      tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization
      specificities indicated that four samples had antibodies with multiple epitope
      binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3
      regions and membrane proximal external region (MPER). Our findings indicate the
      strong possibility of identifying highly potent bNAbs with known or novel
      specificities from HIV-1 subtype C infected individuals from India that can be
      exploited as therapeutic tools or lead molecules for the identification of
      potential epitopes for design of a protective HIV-1 vaccine.

PMID- 28436425
TI  - Monocyte differentiation and antigen-presenting functions.
AB  - Monocytes develop in the bone marrow and represent the primary type of
      mononuclear phagocyte found in the blood. They were long thought of as a source
      for tissue macrophages, but recent studies indicate more complex roles for
      monocytes, both within the circulation and after their migration into tissues and
      lymphoid organs. In this Review, we discuss the newer concepts underlying the
      maturation of emigrating monocytes into different classes of tissue macrophages,
      as well as their potential functions, as monocyte-derived cells, in the tissues.
      In addition, we consider the emerging roles for monocytes in adaptive immunity as
      antigen-presenting cells.

PMID- 28436429
TI  - Human fetal heart specific coexpression network involves congenital heart
      disease/defect candidate genes.
AB  - Heart development is a complex process requiring dynamic transcriptional
      regulation. Disturbance of this process will lead to severe developmental defects
      such as congenital heart disease/defect (CHD). CHD is a group of complex disorder
      with high genetic heterogeneity, common pathways associated with CHD remains
      largely unknown. In the manuscript, we focused on the tissue specific genes in
      human fetal heart samples to explore such pathways. We used the RNA microarray
      dataset of human fetal tissues from ENCODE project to identify genes with heart
      tissue specific expression. A transcriptional network was constructed for these
      genes based on the Pearson correlation coefficients of their expression levels.
      Function, selective constraints and disease associations of these genes were then
      examined. Our analysis identified a network consisted of 316 genes with human
      fetal heart specific expression. The network was highly co-regulated and showed
      evolutionary conserved tissue expression pattern in tetrapod. Genes in this
      network are enriched in CHD specific genes and disease mutations. Using the
      transcriptomic data, we discovered a highly concerted gene network that might
      reflect a common pathway associated with the etiology of CHD. Such analysis
      should be helpful for disease associated gene identification in clinical studies.

PMID- 28436430
TI  - Photostriction of strontium ruthenate.
AB  - Transition metal oxides with a perovskite crystal structure exhibit a variety of
      physical properties associated with the lattice. Among these materials, strontium
      ruthenate (SrRuO3) displays unusually strong coupling of charge, spin and lattice
      degrees of freedom that can give rise to the photostriction, that is, changes in
      the dimensions of material due to the absorption of light. In this study, we
      observe a photon-induced strain as high as 1.12% in single domain SrRuO3, which
      we attribute to a nonequilibrium of phonons that are a result of the strong
      interaction between the crystalline lattice and electrons excited by light. In
      addition, these light-induced changes in the SrRuO3 lattice affect its electrical
      resistance. The observation of both photostriction and photoresistance in SrRuO3
      suggests the possibility of utilizing the mechanical and optical functionalities
      of the material for next-generation optoelectronics, such as remote switches,
      light-controlled elastic micromotors, microactuators and other optomechanical
      systems.

PMID- 28436428
TI  - Neuronal IFN-beta-induced PI3K/Akt-FoxA1 signalling is essential for generation
      of FoxA1+Treg cells.
AB  - Neurons reprogramme encephalitogenic T cells (Tenc) to regulatory T cells
      (Tregs), either FoxP3+Tregs or FoxA1+Tregs. We reported previously that neuronal
      ability to generate FoxA1+Tregs was central to preventing neuroinflammation in
      experimental autoimmune encephalomyelitis (EAE). Mice lacking interferon (IFN)
      beta were defective in generating FoxA1+Tregs in the brain. Here we show that
      lack of neuronal IFNbeta signalling is associated with the absence of programme
      death ligand-1 (PDL1), which prevents their ability to reprogramme Tenc cells to
      FoxA1+Tregs. Passive transfer-EAE via IFNbeta-competent Tenc cells to mice
      lacking IFNbeta and active induced-EAE in mice lacking its receptor, IFNAR, in
      the brain (NesCre:Ifnarfl/fl) result in defective FoxA1+Tregs generation and
      aggravated neuroinflammation. IFNbeta activates neuronal PI3K/Akt signalling and
      Akt binds to transcription factor FoxA1 that translocates to the nucleus and
      induces PDL1. Conversely, inhibition of PI3K/Akt, FoxA1 and PDL1 blocked neuronal
      ability to generate FoxA1+Tregs. We characterize molecular factors central for
      neuronal ability to reprogramme pathogenic T cells to FoxA1+Tregs preventing
      neuroinflammation.

PMID- 28436432
TI  - Band structure engineered layered metals for low-loss plasmonics.
AB  - Plasmonics currently faces the problem of seemingly inevitable optical losses
      occurring in the metallic components that challenges the implementation of
      essentially any application. In this work, we show that Ohmic losses are reduced
      in certain layered metals, such as the transition metal dichalcogenide TaS2, due
      to an extraordinarily small density of states for scattering in the near-IR
      originating from their special electronic band structure. On the basis of this
      observation, we propose a new class of band structure engineered van der Waals
      layered metals composed of hexagonal transition metal chalcogenide-halide layers
      with greatly suppressed intrinsic losses. Using first-principles calculations, we
      show that the suppression of optical losses lead to improved performance for thin
      film waveguiding and transformation optics.

PMID- 28436431
TI  - DNA single-strand break-induced DNA damage response causes heart failure.
AB  - The DNA damage response (DDR) plays a pivotal role in maintaining genome
      integrity. DNA damage and DDR activation are observed in the failing heart,
      however, the type of DNA damage and its role in the pathogenesis of heart failure
      remain elusive. Here we show the critical role of DNA single-strand break (SSB)
      in the pathogenesis of pressure overload-induced heart failure. Accumulation of
      unrepaired SSB is observed in cardiomyocytes of the failing heart. Unrepaired SSB
      activates DDR and increases the expression of inflammatory cytokines through NF
      kappaB signalling. Pressure overload-induced heart failure is more severe in the
      mice lacking XRCC1, an essential protein for SSB repair, which is rescued by
      blocking DDR activation through genetic deletion of ATM, suggesting the causative
      role of SSB accumulation and DDR activation in the pathogenesis of heart failure.
      Prevention of SSB accumulation or persistent DDR activation may become a new
      therapeutic strategy against heart failure.

PMID- 28436433
TI  - Pathways and Genes Associated with Immune Dysfunction in Sheep Paratuberculosis.
AB  - Multibacillary and paucibacillary paratuberculosis are both caused by
      Mycobacterium avium subspecies paratuberculosis. Multibacillary lesions are
      composed largely of infected epithelioid macrophages and paucibacillary lesions
      contain T cells but few bacteria. Multibacillary disease is similar to human
      lepromatous leprosy, with variable/high levels of antibody and a dysfunctional
      immune response. Animals with paucibacillary disease have high cell-mediated
      immunity and variable levels of antibody. This study aims to characterize the
      immunological dysfunction using TruSeq analysis of the ileocaecal lymph node that
      drains disease lesions. Immune dysfunction is highlighted by repression of
      TCR/CD3 genes, T cell co-receptors/co-stimulators, T cell activation and signal
      transduction genes. Inflammation was an acute phase response and chronic
      inflammation, with little evidence of acute inflammation. The high levels of
      immunoglobulin and plasma cell transcripts is consistent with the anti-MAP
      antibody responses in paratuberculosis sheep. Also notable was the overwhelming
      reduction in mast cell transcripts, potentially affecting DC activation of the
      immune response. This study also shows that there were no fundamental differences
      in the gene expression patterns in multibacillary and paucibacillary disease, no
      shift in T cell genes from Th1 to Th2 pattern but rather an incremental decline
      into immune dysfunction leading to multibacillary pathology.

PMID- 28436434
TI  - Phosphatidylethanolamine dynamics are required for osteoclast fusion.
AB  - Osteoclasts, responsible for bone resorption, are multinucleated cells formed by
      cell-cell fusion of mononuclear pre-osteoclasts. Although osteoclast fusion is a
      pivotal step for osteoclastogenesis, little is known about the mechanism
      involved. To clarify the underlying process, we investigated dynamics of membrane
      phospholipids during osteoclastogenesis in vitro. We found that the cellular
      content of phospholipids, phosphatidylethanolamine (PE) in particular, was
      increased during osteoclast differentiation. Furthermore, PE was greatly
      increased in the outer leaflet of the plasma membrane bilayer during
      osteoclastogenesis, being concentrated in filopodia involved in cell-cell fusion.
      Immobilisation of the cell surface PE blocked osteoclast fusion, revealing the
      importance of PE abundance and distribution. To identify the molecules
      responsible for these PE dynamics, we screened a wide array of lipid-related
      genes by quantitative PCR and shRNA-mediated knockdown. Among them, a PE
      biosynthetic enzyme, acyl-CoA:lysophosphatidylethanolamine acyltransferase 2
      (LPEAT2), and two ATP-binding cassette (ABC) transporters, ABCB4 and ABCG1, were
      markedly increased during osteoclastogenesis, and their knockdown in pre
      osteoclasts led to reduction in PE exposure on the cell surface and subsequent
      osteoclast fusion. These findings demonstrate that the PE dynamics play an
      essential role in osteoclast fusion, in which LPEAT2, ABCB4 and ABCG1 are key
      players for PE biosynthesis and redistribution.

PMID- 28436435
TI  - Structure and function of the divalent anion/Na+ symporter from Vibrio cholerae
      and a humanized variant.
AB  - Integral membrane proteins of the divalent anion/Na+ symporter (DASS) family
      translocate dicarboxylate, tricarboxylate or sulphate across cell membranes,
      typically by utilizing the preexisting Na+ gradient. The molecular determinants
      for substrate recognition by DASS remain obscure, largely owing to the absence of
      any substrate-bound DASS structure. Here we present 2.8-A resolution X-ray
      structures of VcINDY, a DASS from Vibrio cholerae that catalyses the co-transport
      of Na+ and succinate. These structures portray the Na+-bound VcINDY in complexes
      with succinate and citrate, elucidating the binding sites for substrate and two
      Na+ ions. Furthermore, we report the structures of a humanized variant of VcINDY
      in complexes with succinate and citrate, which predict how a human citrate
      transporting DASS may interact with its bound substrate. Our findings provide
      insights into metabolite transport by DASS, establishing a molecular basis for
      future studies on the regulation of this transport process.

PMID- 28436436
TI  - Time-reversal symmetry breaking hidden order in Sr2(Ir,Rh)O4.
AB  - Layered 5d transition iridium oxides, Sr2(Ir,Rh)O4, are described as
      unconventional Mott insulators with strong spin-orbit coupling. The undoped
      compound, Sr2IrO4, is a nearly ideal two-dimensional pseudospin-1/2 Heisenberg
      antiferromagnet, similarly to the insulating parent compound of high-temperature
      superconducting copper oxides. Using polarized neutron diffraction, we here
      report a hidden magnetic order in pure and doped Sr2(Ir,Rh)O4, distinct from the
      usual antiferromagnetic pseudospin ordering. We find that time-reversal symmetry
      is broken while the lattice translation invariance is preserved in the hidden
      order phase. The onset temperature matches that of the odd-parity hidden order
      recently highlighted using optical second-harmonic generation experiments. The
      novel magnetic order and broken symmetries can be explained by the loop-current
      model, previously predicted for the copper oxide superconductors.

PMID- 28436437
TI  - Allele-Selective Suppression of Mutant Huntingtin in Primary Human Blood Cells.
AB  - Post-transcriptional gene silencing is a promising therapy for the monogenic,
      autosomal dominant, Huntington's disease (HD). However, wild-type huntingtin
      (HTT) has important cellular functions, so the ideal strategy would selectively
      lower mutant HTT while sparing wild-type. HD patients were genotyped for
      heterozygosity at three SNP sites, before phasing each SNP allele to wild-type or
      mutant HTT. Primary ex vivo myeloid cells were isolated from heterozygous
      patients and transfected with SNP-targeted siRNA, using glucan particles taken up
      by phagocytosis. Highly selective mRNA knockdown was achieved when targeting each
      allele of rs362331 in exon 50 of the HTT transcript; this selectivity was also
      present on protein studies. However, similar selectivity was not observed when
      targeting rs362273 or rs362307. Furthermore, HD myeloid cells are hyper-reactive
      compared to control. Allele-selective suppression of either wild-type or mutant
      HTT produced a significant, equivalent reduction in the cytokine response of HD
      myeloid cells to LPS, suggesting that wild-type HTT has a novel immune function.
      We demonstrate a sequential therapeutic process comprising genotyping and mutant
      HTT-linkage of SNPs, followed by personalised allele-selective suppression in a
      small patient cohort. We further show that allele-selectivity in ex vivo patient
      cells is highly SNP-dependent, with implications for clinical trial target
      selection.

PMID- 28436438
TI  - Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper
      Hollow Silica Nanoparticles.
AB  - Combination chemotherapy has become the primary strategy against cancer multidrug
      resistance; however, accomplishing optimal pharmacokinetic delivery of multiple
      drugs is still challenging. Herein, we report a sequential combination drug
      delivery strategy exploiting a pH-triggerable and redox switch to release cargos
      from hollow silica nanoparticles in a spatiotemporal manner. This versatile
      system further enables a large loading efficiency for both hydrophobic and
      hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with
      disulfide and diisopropylamine-functionalized polymers. In acidic tumour
      environments, the positive charge generated by the protonation of the
      diisopropylamine moiety facilitated the cellular uptake of the particles. Upon
      internalization, the acidic endosomal pH condition and intracellular glutathione
      regulated the sequential release of the drugs in a time-dependent manner,
      providing a promising therapeutic approach to overcoming drug resistance during
      cancer treatment.

PMID- 28436439
TI  - Discovery of tauroursodeoxycholic acid biotransformation enzymes from the gut
      microbiome of black bears using metagenomics.
AB  - Tauroursodeoxycholic acid (TUDCA) has been used to treat many diseases
      effectively. 7alpha-hydroxysteroid dehydrogenase (7alpha-HSDH) and 7beta
      hydroxysteroid dehydrogenase (7beta-HSDH) are two key enzymes that drive the
      efficient biosynthesis of TUDCA from taurochenodeoxycholic acid (TCDCA) in vitro.
      In this study, a metagenomic approach was used to isolate 7alpha- and 7beta-HSDHs
      from fecal samples of black bears. Five new 7alpha-HSDHs and one new 7beta-HSDH
      enzyme were discovered and identified from the gut microbiota of black bears, and
      four of them presented good enzymatic properties. Our data also suggest
      cooperation in the biotransformation of TUDCA by the gut microbiota in black
      bears. In conclusion, this work expands the natural enzyme bank of HSDHs,
      provides promising candidate enzymes for application in the biosynthesis TUDCA
      and the epimerization reaction of bile acids at the C-7 position, and provides a
      data set for the discovery of novel enzymes in the gut micriobiome of black
      bears.

PMID- 28436440
TI  - A metallic molybdenum dioxide with high stability for surface enhanced Raman
      spectroscopy.
AB  - Compared with noble metals, semiconductors with surface plasmon resonance effect
      are another type of SERS substrate materials. The main obstacles so far are that
      the semiconducting materials are often unstable and easy to be further oxidized
      or decomposed by laser irradiating or contacting with corrosive substances. Here,
      we report that metallic MoO2 can be used as a SERS substrate to detect trace
      amounts of highly risk chemicals including bisphenol A (BPA), dichloropheno
      (DCP), pentachlorophenol (PCP) and so on. The minimum detectable concentration
      was 10-7 M and the maximum enhancement factor is up to 3.75 * 106. To the best of
      our knowledge, it may be the best among the metal oxides and even reaches or
      approaches to Au/Ag. The MoO2 shows an unexpected high oxidation resistance,
      which can even withstand 300  degrees C in air without further oxidation. The
      MoO2 material also can resist long etching of strong acid and alkali.

PMID- 28436441
TI  - Erratum: CD40-signalling abrogates induction of RORgammat+ Treg cells by
      intestinal CD103+ DCs and causes fatal colitis.

PMID- 28436442
TI  - Thermal stability, storage and release of proteins with tailored fit in silica.
AB  - Biological substances based on proteins, including vaccines, antibodies, and
      enzymes, typically degrade at room temperature over time due to denaturation, as
      proteins unfold with loss of secondary and tertiary structure. Their storage and
      distribution therefore relies on a "cold chain" of continuous refrigeration; this
      is costly and not always effective, as any break in the chain leads to rapid loss
      of effectiveness and potency. Efforts have been made to make vaccines thermally
      stable using treatments including freeze-drying (lyophilisation),
      biomineralisation, and encapsulation in sugar glass and organic polymers. Here
      for the first time we show that proteins can be enclosed in a deposited silica
      "cage", rendering them stable against denaturing thermal treatment and long-term
      ambient-temperature storage, and subsequently released into solution with their
      structure and function intact. This "ensilication" method produces a storable
      solid protein-loaded material without the need for desiccation or freeze-drying.
      Ensilication offers the prospect of a solution to the "cold chain" problem for
      biological materials, in particular for vaccines.

PMID- 28436443
TI  - Curcumol allosterically modulates GABA(A) receptors in a manner distinct from
      benzodiazepines.
AB  - Inhibitory A type gamma-aminobutyric acid receptors (GABAARs) play a pivotal role
      in orchestrating various brain functions and represent an important molecular
      target in neurological and psychiatric diseases, necessitating the need for the
      discovery and development of novel modulators. Here, we show that a natural
      compound curcumol, acts as an allosteric enhancer of GABAARs in a manner distinct
      from benzodiazepines. Curcumol markedly facilitated GABA-activated currents and
      shifted the GABA concentration-response curve to the left in cultured hippocampal
      neurons. When co-applied with the classical benzodiazepine diazepam, curcumol
      further potentiated GABA-induced currents. In contrast, in the presence of a
      saturating concentration of menthol, a positive modulator for GABAAR, curcumol
      failed to further enhance GABA-induced currents, suggesting shared mechanisms
      underlying these two agents on GABAARs. Moreover, the benzodiazepine antagonist
      flumazenil did not alter the enhancement of GABA response by curcumol and
      menthol, but abolished that by DZP. Finally, mutations at the beta2 or gamma2
      subunit predominantly eliminated modulation of recombinant GABAARs by curcumol
      and menthol, or diazepam, respectively. Curcumol may therefore exert its actions
      on GABAARs at sites distinct from benzodiazepine sites. These findings shed light
      on the future development of new therapeutics drugs targeting GABAARs.

PMID- 28436444
TI  - Transcriptome profiling of sulfate deprivation responses in two agarophytes
      Gracilaria changii and Gracilaria salicornia (Rhodophyta).
AB  - Seaweeds survive in marine waters with high sulfate concentration compared to
      those living at freshwater habitats. The cell wall polymer of Gracilaria spp.
      which supplies more than 50% of the world agar is heavily sulfated. Since
      sulfation reduces the agar quality, it is interesting to investigate the effects
      of sulfate deprivation on the sulfate contents of seaweed and agar, as well as
      the metabolic pathways of these seaweeds. In this study, two agarophytes G.
      changii and G. salicornia were treated under sulfate deprivation for 5 days. The
      sulfate contents in the seaweed/agar were generally lower in sulfate-deprivated
      samples compared to those in the controls, but the differences were only
      statistically significant for seaweed sample of G. changii and agar sample of G.
      salicornia. RNA sequencing (RNA-Seq) of sulfate-deprivated and untreated seaweed
      samples revealed 1,292 and 3,439 differentially expressed genes (DEGs; >=1.5
      fold) in sulfate-deprivated G. changii and G. salicornia, respectively, compared
      to their respective controls. Among the annotated DEGs were genes involved in
      putative agar biosynthesis, sulfur metabolism, metabolism of sulfur-containing
      amino acids, carbon metabolism and oxidative stress. These findings shed light on
      the sulfate deprivation responses in agarophytes and help to identify candidate
      genes involved in agar biosynthesis.

PMID- 28436445
TI  - Cortical Thickness and Subcortical Gray Matter Volume in Pediatric Anxiety
      Disorders.
AB  - Perturbations in the prefrontal cortex (PFC), hippocampus, and amygdala are
      implicated in the development of anxiety disorders. However, most structural
      neuroimaging studies of patients with anxiety disorders utilize adult samples,
      and the few studies in youths examine small samples, primarily with volume-based
      measures. This study tested the hypothesis that cortical thickness of PFC regions
      and gray matter volume of the hippocampus and amygdala differ between pediatric
      anxiety disorder patients and healthy volunteers (HVs). High-resolution 3-Tesla
      T1-weighted MRI scans were acquired in 151 youths (75 anxious, 76 HV; ages 8-18).
      Analyses tested associations of brain structure with anxiety diagnosis and
      severity across both groups, as well as response to cognitive-behavioral therapy
      in a subset of 53 patients. Cortical thickness was evaluated both within an a
      priori PFC mask (small-volume corrected) and using an exploratory whole-brain
      corrected (p<0.05) approach. Anxious relative to healthy youths exhibited thicker
      cortex in the left ventromedial PFC (vmPFC) and left precentral gyrus. Both
      anxiety diagnosis and symptom severity were associated with smaller right
      hippocampal volume. In patients, thinner cortex in parietal and occipital
      cortical regions was associated with worse treatment response. Pediatric anxiety
      was associated with structural differences in vmPFC and hippocampus, regions
      implicated in emotional processing and in developmental models of anxiety
      pathophysiology. Parietal and occipital cortical thickness were related to
      anxiety treatment response but not baseline anxiety.

PMID- 28436446
TI  - Opioid Self-Administration is Attenuated by Early-Life Experience and Gene
      Therapy for Anti-Inflammatory IL-10 in the Nucleus Accumbens of Male Rats.
AB  - Early-life conditions can contribute to the propensity for developing
      neuropsychiatric disease, including substance abuse disorders. However, the long
      lasting mechanisms that shape risk or resilience for drug addiction remain
      unclear. Previous work has shown that a neonatal handling procedure in rats
      (which promotes enriched maternal care) attenuates morphine conditioning, reduces
      morphine-induced glial activation, and increases microglial expression of the
      anti-inflammatory cytokine interleukin-10 (IL-10). We thus hypothesized that anti
      inflammatory signaling may underlie the effects of early-life experience on later
      life opioid drug-taking. Here we demonstrate that neonatal handling attenuates
      intravenous self-administration of the opioid remifentanil in a drug
      concentration-dependent manner. Transcriptional profiling of the nucleus
      accumbens (NAc) from handled rats following repeated exposure to remifentanil
      reveals a suppression of pro-inflammatory cytokine and chemokine gene expression,
      consistent with an anti-inflammatory phenotype. To determine if anti-inflammatory
      signaling alters drug-taking behavior, we administered intracranial injections of
      plasmid DNA encoding IL-10 (pDNA-IL-10) into the NAc of non-handled rats. We
      discovered that pDNA-IL-10 treatment reduces remifentanil self-administration in
      a drug-concentration-dependent manner, similar to the effect of handling. In
      contrast, neither handling nor pDNA-IL-10 treatment alters self-administration of
      food or sucrose rewards. These collective observations suggest that neuroimmune
      signaling mechanisms in the NAc are shaped by early-life experience and may
      modify motivated behaviors for opioid drugs. Moreover, manipulation of the IL-10
      signaling pathway represents a novel approach for influencing opioid
      reinforcement.

PMID- 28436447
TI  - An integrated double-filtration microfluidic device for isolation, enrichment and
      quantification of urinary extracellular vesicles for detection of bladder cancer.
AB  - Extracellular vesicles (EVs), including exosomes and microvesicles, are present
      in a variety of bodily fluids, and the concentration of these sub-cellular
      vesicles and their associated biomarkers (proteins, nucleic acids, and lipids)
      can be used to aid clinical diagnosis. Although ultracentrifugation is commonly
      used for isolation of EVs, it is highly time-consuming, labor-intensive and
      instrument-dependent for both research laboratories and clinical settings. Here,
      we developed an integrated double-filtration microfluidic device that isolated
      and enriched EVs with a size range of 30-200 nm from urine, and subsequently
      quantified the EVs via a microchip ELISA. Our results showed that the
      concentration of urinary EVs was significantly elevated in bladder cancer
      patients (n = 16) compared to healthy controls (n = 8). Receiver operating
      characteristic (ROC) analysis demonstrated that this integrated EV double
      filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder
      cancer patients and 8 healthy controls). Thus, this integrated device has great
      potential to be used in conjunction with urine cytology and cystoscopy to improve
      clinical diagnosis of bladder cancer in clinics and at point-of-care (POC)
      settings.

PMID- 28436448
TI  - Elevated circulating levels of the interferon-gamma-induced chemokines are
      associated with disease activity and cutaneous manifestations in adult-onset
      Still's disease.
AB  - C-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 are produced in response to
      interferon-gamma (IFN-gamma) and trigger inflammation with the accumulation of
      activated lymphocytes. It appears that these chemokines could play a role in the
      pathogenesis of adult-onset Still's disease (AOSD). Therefore, we investigated
      the associations between the levels of these chemokine and clinical
      manifestations in patients with active AOSD. Serum levels of IFN-gamma, CXCL9,
      CXCL10 and CXCL11 were determined using enzyme-linked immunosorbent assays. IFN
      gamma levels were higher in AOSD patients than in rheumatoid arthritis (RA)
      patients (p = 0.001) or healthy controls (HCs) (p = 0.032). AOSD patients also
      exhibited higher levels of CXCL9, CXCL10, and CXCL11 compared with RA patients (p
      < 0.001) and HCs (p < 0.001). In follow-up AOSD patients after treatment with
      corticosteroid, the levels of CXCL9, CXCL10 and CXCL11 fell significantly,
      whereas IFN-gamma levels were not significantly different. On
      immunohistochemistry, the percentage of CXCL10-positive inflammatory cells was
      higher in skin biopsy samples from AOSD patients than in those from normal
      control (p = 0.012), eczema (p = 0.019), and psoriasis (p = 0.009) groups. Levels
      of the IFN-gamma-induced chemokines, CXCL9, CXCL10 and CXCL11, were elevated and
      correlated with several disease activity markers. These interferon-gamma-induced
      chemokines may contribute to inflammatory responses and skin manifestations in
      AOSD.

PMID- 28436450
TI  - Definition of fractal topography to essential understanding of scale-invariance.
AB  - Fractal behavior is scale-invariant and widely characterized by fractal
      dimension. However, the cor-respondence between them is that fractal behavior
      uniquely determines a fractal dimension while a fractal dimension can be related
      to many possible fractal behaviors. Therefore, fractal behavior is independent of
      the fractal generator and its geometries, spatial pattern, and statistical
      properties in addition to scale. To mathematically describe fractal behavior, we
      propose a novel concept of fractal topography defined by two scale-invariant
      parameters, scaling lacunarity (P) and scaling coverage (F). The scaling
      lacunarity is defined as the scale ratio between two successive fractal
      generators, whereas the scaling coverage is defined as the number ratio between
      them. Consequently, a strictly scale-invariant definition for self-similar
      fractals can be derived as D = log F /log P. To reflect the direction-dependence
      of fractal behaviors, we introduce another parameter Hxy, a general Hurst
      exponent, which is analytically expressed by Hxy = log Px/log Py where Px and Py
      are the scaling lacunarities in the x and y directions, respectively. Thus, a
      unified definition of fractal dimension is proposed for arbitrary self-similar
      and self-affine fractals by averaging the fractal dimensions of all directions in
      a d-dimensional space, which . Our definitions provide a theoretical, mechanistic
      basis for understanding the essentials of the scale-invariant property that
      reduces the complexity of modeling fractals.

PMID- 28436449
TI  - Metabolism dysregulation induces a specific lipid signature of nonalcoholic
      steatohepatitis in patients.
AB  - Nonalcoholic steatohepatitis (NASH) is a condition which can progress to
      cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still
      lacking. We performed a comprehensive lipidomic analysis on human liver biopsies
      including normal liver, nonalcoholic fatty liver and NASH. Random forests-based
      machine learning approach allowed characterizing a signature of 32 lipids
      discriminating NASH with 100% sensitivity and specificity. Furthermore, we
      validated this signature in an independent group of NASH patients. Then,
      metabolism dysregulations were investigated in both patients and murine models.
      Alterations of elongase and desaturase activities were observed along the fatty
      acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared
      as a bottleneck, leading upstream to an accumulation of fatty acids and
      downstream to a deficiency of long-chain fatty acids resulting to impaired
      phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section
      revealed the spreading into the hepatic parenchyma of selectively accumulated
      fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes.
      In conclusion, this study characterized a specific and sensitive lipid signature
      of NASH and positioned FADS1 as a significant player in accumulating toxic lipids
      during NASH progression.

PMID- 28436451
TI  - Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide
      Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts.
AB  - Carcinogenesis is a complex molecular process starting with genetic and
      epigenetic alterations, mutation stimulation, and DNA modification, which leads
      to proteomic adaptation ending with an uncontrolled proliferation mechanism. The
      current research focused on the empirical modelling of the physiological response
      of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to
      the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate
      this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip
      silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX
      conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma
      (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure.
      Interestingly, significant cell necrosis was observed because of a loss in
      mitochondrial membrane potential just after insertion of the femtotip tool.
      Intense reactive oxygen species (ROS) fluorescence was observed after exposure to
      the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were
      verified by applying several experimental techniques, e.g., ROS detection, MTT
      assay, and fluorescence spectroscopy. The present work reports experimental
      modelling of cell necrosis in normal human skin as well as a cancerous tissue.
      These obtained results pave the way for a more rational strategy for biomedical
      and clinical applications.

PMID- 28436453
TI  - Functional, thermodynamics, structural and biological studies of in silico
      identified inhibitors of Mycobacterium tuberculosis enoyl-ACP(CoA) reductase
      enzyme.
AB  - Novel chemotherapeutics agents are needed to kill Mycobacterium tuberculosis, the
      main causative agent of tuberculosis (TB). The M. tuberculosis 2-trans-enoyl
      ACP(CoA) reductase enzyme (MtInhA) is the druggable bona fide target of
      isoniazid. New chemotypes were previously identified by two in silico approaches
      as potential ligands to MtInhA. The inhibition mode was determined by steady
      state kinetics for seven compounds that inhibited MtInhA activity. Dissociation
      constant values at different temperatures were determined by protein fluorescence
      spectroscopy. van't Hoff analyses of ligand binding to MtInhA:NADH provided the
      thermodynamic signatures of non-covalent interactions (DeltaH degrees , DeltaS
      degrees , DeltaG degrees ). Phenotypic screening showed that five compounds
      inhibited in vitro growth of M. tuberculosis H37Rv strain. Labio_16 and Labio_17
      compounds also inhibited the in vitro growth of PE-003 multidrug-resistant
      strain. Cytotoxic effects on Hacat, Vero and RAW 264.7 cell lines were assessed
      for the latter two compounds. The Labio_16 was bacteriostatic and Labio_17
      bactericidal in an M. tuberculosis-infected macrophage model. In Zebrafish model,
      Labio_16 showed no cardiotoxicity whereas Labio_17 showed dose-dependent
      cardiotoxicity. Accordingly, a model was built for the MtInhA:NADH:Labio_16
      ternary complex. The results show that the Labio_16 compound is a direct
      inhibitor of MtInhA, and it may represent a hit for the development of
      chemotherapeutic agents to treat TB.

PMID- 28436452
TI  - Disrupted neuronal maturation in Angelman syndrome-derived induced pluripotent
      stem cells.
AB  - Angelman syndrome (AS) is a neurogenetic disorder caused by deletion of the
      maternally inherited UBE3A allele and is characterized by developmental delay,
      intellectual disability, ataxia, seizures and a happy affect. Here, we explored
      the underlying pathophysiology using induced pluripotent stem cell-derived
      neurons from AS patients and unaffected controls. AS-derived neurons showed
      impaired maturation of resting membrane potential and action potential firing,
      decreased synaptic activity and reduced synaptic plasticity. These patient
      specific differences were mimicked by knocking out UBE3A using CRISPR/Cas9 or by
      knocking down UBE3A using antisense oligonucleotides. Importantly, these
      phenotypes could be rescued by pharmacologically unsilencing paternal UBE3A
      expression. Moreover, selective effects of UBE3A disruption at late stages of in
      vitro development suggest that changes in action potential firing and synaptic
      activity may be secondary to altered resting membrane potential. Our findings
      provide a cellular phenotype for investigating pathogenic mechanisms underlying
      AS and identifying novel therapeutic strategies.

PMID- 28436454
TI  - Gold nanoparticle-polymer nanocomposites synthesized by room temperature
      atmospheric pressure plasma and their potential for fuel cell electrocatalytic
      application.
AB  - Conductive polymers have been increasingly used as fuel cell catalyst support due
      to their electrical conductivity, large surface areas and stability. The
      incorporation of metal nanoparticles into a polymer matrix can effectively
      increase the specific surface area of these materials and hence improve the
      catalytic efficiency. In this work, a nanoparticle loaded conductive polymer
      nanocomposite was obtained by a one-step synthesis approach based on room
      temperature direct current plasma-liquid interaction. Gold nanoparticles were
      directly synthesized from HAuCl4 precursor in poly(3,4-ethylenedioxythiophene)
      polystyrene sulfonate (PEDOT:PSS). The resulting AuNPs/PEDOT:PSS nanocomposites
      were subsequently characterized under a practical alkaline direct ethanol fuel
      cell operation condition for its potential application as an electrocatalyst.
      Results show that AuNPs sizes within the PEDOT:PSS matrix are dependent on the
      plasma treatment time and precursor concentration, which in turn affect the
      nanocomposites electrical conductivity and their catalytic performance. Under
      certain synthesis conditions, unique nanoscale AuNPs/PEDOT:PSS core-shell
      structures could also be produced, indicating the interaction at the
      AuNPs/polymer interface. The enhanced catalytic activity shown by AuNPs/PEDOT:PSS
      has been attributed to the effective electron transfer and reactive species
      diffusion through the porous polymer network, as well as the synergistic
      interfacial interaction at the metal/polymer and metal/metal interfaces.

PMID- 28436455
TI  - The impact of gold mining and agricultural concessions on the tree cover and
      local communities in northern Myanmar.
AB  - Myanmar offers unique opportunities for both biodiversity conservation and
      foreign direct investment due to projected economic growth linked to natural
      resource exploitation. Industrial-scale development introduces new land uses into
      the landscape, with unknown repercussions for local communities and biodiversity
      conservation. We use participatory mapping of 31 communities, focus groups in 28
      communities, and analyses of forest cover change during 2000-2010 using MODIS
      vegetation continuous fields images, to understand the social and environmental
      impacts of gold mining and agricultural concessions in Myanmar's Hukaung Valley
      (~21,800 km2). Local communities, particularly the poorest households, benefit
      from work and trade opportunities offered by gold mining and agricultural
      companies but continue to depend on forests for house construction materials,
      food, and income from the sale of forest resources. However, gold mining and
      agricultural concessions reduce tree cover, potentially reducing access to forest
      resources and further marginalizing these households. Our analyses do not provide
      evidence that long-term resident communities contributed to forest cover loss
      between 2000 and 2010. We argue that landscape management, which recognizes local
      community rights to customary community use areas, and appropriate zoning for
      commercial land uses and protected areas could contribute to both local
      livelihoods and protect biodiversity throughout Myanmar during economic growth.

PMID- 28436456
TI  - Synthesis and anti-obesity effects in vivo of Crotadihydrofuran C as a novel
      PPARgamma antagonist from Crotalaria albida.
AB  - Crotadihydrofuran C (CC) from the herbs of Crotalaria albida is able to inhibit
      adipocyte differentiation and lipid accumulation. However, the effects of CC on
      obesity and metabolic disorders have not yet been elucidated. In our study, the
      first enantioselective synthesis of the 2-isopropenyl dihydrofuran isoflavone
      skeleton (CC) is described. The convenient and efficient synthetic protocols
      developed skilfully solve the problems of the ortho-para directing group and
      Suzuki coupling reaction using a boronic acid pinacol ester that was more stable
      and easy to obtain. Furthermore, CC treatment of high-fat diet (HFD)-fed obese
      mice remarkably reduced their body weight, fat mass, and lipid level as well as
      improved insulin resistance and non-alcoholic fatty liver disease (NAFLD). A TR
      FRET assay showed that CC was specifically bound to PPARgamma LBD, which was
      further confirmed by the molecular docking study. These results suggest that CC
      could be a useful and potential natural product for treating metabolic diseases,
      including obesity, hyperlipidemia insulin resistance and NAFLD, without toxic
      side-effects.

PMID- 28436457
TI  - Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the
      Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin
      inducing T cell anergy.
AB  - Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a
      variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse
      range of pathogens, including parasites. The interaction of DC-SIGN with
      pathogens triggers specific signaling events that modulate DC-maturation and
      activity and regulate T-cell activation by DCs. In this work we evaluate whether
      F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC
      SIGN interacts with F. hepatica glycoconjugates through mannose and fucose
      residues. We also show that mannose is present in high-mannose structures, hybrid
      and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that
      F. hepatica glycans induce DC-SIGN triggering leading to a strong production of
      TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory
      DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction
      of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation
      of innate and adaptive immune responses by F. hepatica. Our data confirm the
      immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and
      contribute to the identification of immunomodulatory glyans of helminths that
      might eventually be useful for the design of vaccines against fasciolosis.

PMID- 28436458
TI  - Development of a fluorescent ASFV strain that retains the ability to cause
      disease in swine.
AB  - African swine fever is a contagious and often lethal disease for domestic pigs
      with a significant economic impact for the swine industry. The etiological agent,
      African swine fever virus (ASFV), is a highly structurally complex double
      stranded DNA virus. No effective vaccines or antiviral treatment are currently
      commercially available. We present here the development of a strain of ASFV that
      has been shown to retain its ability to cause disease in swine, efficiently
      replicate in swine macrophage and that is fluorescently tagged. The insertion of
      an EGFP cassette replacing the reading frames for two neighboring genes, MGF360
      13L and MGF360-14L, in highly virulent field isolate Georgia/2007, did not affect
      virus replication in cell cultures and did not affect disease progression in
      swine, the natural host for ASFV. A virulent fluorescently tagged ASFV is a
      suitable tool to conduct pathogenesis studies in swine, study on virus-macrophage
      interaction and to run large scale screens that require a sensitive high
      throughput output. Utilizing an EGFP reporter system for observing ASFV
      replication and infectivity can circumvent the time and labor-intensive steps
      associated with viral antigen-based assays such as the observation of
      hemadsorption or cytopathic effect.

PMID- 28436459
TI  - Identification of pro-inflammatory CD205+ macrophages in livers of hepatitis B
      virus transgenic mice and patients with chronic hepatitis B.
AB  - Hepatic macrophages play a central role in disease pathogenesis during hepatitis
      B virus (HBV) infection. Our previous study found that CD205+ macrophages in the
      liver of hepatitis B surface antigen transgenic (HBs-Tg) mice increased
      significantly compared with those in wild-type mice, and these increased CD205+
      macrophages were involved in CpG-oligodeoxynucleotide-induced liver injury in HBs
      Tg mice. Here, we analysed the phenotype and function of CD205+ macrophages
      derived from the liver of HBs-Tg mice and patients with chronic hepatitis B
      (CHB). We found that HBs-Tg mice-derived hepatic macrophages produced larger
      amounts of pro-inflammatory cytokines, including IL-6, IL-12, TNF-alpha, and of
      the anti-inflammatory cytokine IL-10 after stimulation with CpG
      oligodeoxynucleotides or commensal bacteria DNA than B6 mice-derived hepatic
      macrophages. Furthermore, hepatic CD205+ macrophages from HBs-Tg mice showed an
      activated phenotype and expressed higher levels of inflammatory cytokine genes,
      chemokine genes, and phagocytosis-related genes than hepatic CD205- macrophages.
      In addition, CD205+ macrophages displayed an inflammatory phenotype and were
      increased in the liver of patients with CHB compared with those in healthy
      controls. Our data suggest that hepatic CD205+ macrophages are a unique pro
      inflammatory subset observed during HBV infection. Thus, development of
      intervention targeting these cells is warranted for immunotherapy of HBV-induced
      liver diseases.

PMID- 28436461
TI  - Photon-phonon-photon transfer in optomechanics.
AB  - We consider transfer of a highly nonclassical quantum state through an
      optomechanical system. That is we investigate a protocol consisting of sequential
      upload, storage and reading out of the quantum state from a mechanical mode of an
      optomechanical system. We show that provided the input state is in a test-bed
      single-photon Fock state, the Wigner function of the recovered state can have
      negative values at the origin, which is a manifest of nonclassicality of the
      quantum state of the macroscopic mechanical mode and the overall transfer
      protocol itself. Moreover, we prove that the recovered state is quantum non
      Gaussian for wide range of setup parameters. We verify that current
      electromechanical and optomechanical experiments can test this complete transfer
      of single photon.

PMID- 28436460
TI  - Histological validation of fast macromolecular proton fraction mapping as a
      quantitative myelin imaging method in the cuprizone demyelination model.
AB  - Cuprizone-induced demyelination in mice is a frequently used model in preclinical
      multiple sclerosis research. A recent quantitative clinically-targeted MRI
      method, fast macromolecular proton fraction (MPF) mapping demonstrated a promise
      as a myelin biomarker in human and animal studies with a particular advantage of
      sensitivity to both white matter (WM) and gray matter (GM) demyelination. This
      study aimed to histologically validate the capability of MPF mapping to quantify
      myelin loss in brain tissues using the cuprizone demyelination model. Whole-brain
      MPF maps were obtained in vivo on an 11.7T animal MRI scanner from 7 cuprizone
      treated and 7 control S57BL/6 mice using the fast single-point synthetic
      reference method. Brain sections were histologically stained with Luxol Fast Blue
      (LFB) for myelin quantification. Significant (p < 0.05) demyelination in
      cuprizone-treated animals was found according to both LFB staining and MPF in all
      anatomical structures (corpus callosum, anterior commissure, internal capsule,
      thalamus, caudoputamen, and cortex). MPF strongly correlated with quantitative
      histology in all animals (r = 0.95, p < 0.001) as well as in treatment and
      control groups taken separately (r = 0.96, p = 0.002 and r = 0.93, p = 0.007,
      respectively). Close agreement between histological myelin staining and MPF
      suggests that fast MPF mapping enables robust and accurate quantitative
      assessment of demyelination in both WM and GM.

PMID- 28436462
TI  - MiR-146b is down-regulated during the chondrogenic differentiation of human bone
      marrow derived skeletal stem cells and up-regulated in osteoarthritis.
AB  - Articular cartilage injury can result in chondrocyte loss and diminishment of
      specialised extracellular matrix, which can progress to an osteoarthritic (OA)
      phenotype. Stem cells have emerged as a favourable approach for articular
      cartilage regeneration. Identification of miRNAs which influence stem cell fate
      offers new approaches for application of miRNAs to regenerate articular
      cartilage. Skeletal stem cells (SSCs) isolated from human bone marrow were
      cultured as high density micromass' using TGF-beta3 to induce chondrogenesis.
      qPCR and TaqMan qPCR were used to assess chondrogenic gene and miRNA expression.
      Target prediction algorithms identified potential targets of miR-146b. Transient
      transfection with miR-146b mimic and western blotting was used to analyse SOX5.
      Human OA articular chondrocytes were examined for miR-146b expression.
      Chondrogenic differentiation of human bone marrow derived SSCs resulted in
      significant down-regulation of miR-146b. Gain of miR-146b function resulted in
      down-regulation of SOX5. MiR-146b expression was up-regulated in OA chondrocytes.
      These findings demonstrate the functional role of miR-146b in the chondrogenic
      differentiation of human bone marrow derived SSCs. MiR-146b may play a role in
      the pathophysiology of OA. Application of miR-146b combined with stem cell
      therapy could enhance regeneration of cartilaginous tissue and serve as a
      potential therapeutic target in the treatment of OA.

PMID- 28436463
TI  - Relation between molecular electronic structure and nuclear spin-induced circular
      dichroism.
AB  - The recently theoretically described nuclear spin-induced circular dichroism
      (NSCD) is a promising method for the optical detection of nuclear magnetization.
      NSCD involves both optical excitations of the molecule and hyperfine interactions
      and, thus, it offers a means to realize a spectroscopy with spatially localized,
      high-resolution information. To survey the factors relating the molecular and
      electronic structure to the NSCD signal, we theoretically investigate NSCD of
      twenty structures of the four most common nucleic acid bases (adenine, guanine,
      thymine, cytosine). The NSCD signal correlates with the spatial distribution of
      the excited states and couplings between them, reflecting changes in molecular
      structure and conformation. This constitutes a marked difference to the nuclear
      magnetic resonance (NMR) chemical shift, which only reflects the local molecular
      structure in the ground electronic state. The calculated NSCD spectra are
      rationalized by means of changes in the electronic density and by a sum-over
      states approach, which allows to identify the contributions of the individual
      excited states. Two separate contributions to NSCD are identified and their
      physical origins and relative magnitudes are discussed. The results underline
      NSCD spectroscopy as a plausible tool with a power for the identification of not
      only different molecules, but their specific structures as well.

PMID- 28436465
TI  - The Clinical Efficacy of Fibrinogen Concentrate in Massive Obstetric Haemorrhage
      with Hypofibrinogenaemia.
AB  - Massive obstetric haemorrhage remains a major cause of maternal death
      attributable to hypofibrinogenaemia. Transfusion of large volumes of fresh frozen
      plasma (FFP) is required to normalise fibrinogen levels. We compared the efficacy
      of FFP (F group) with that of FFP plus fibrinogen concentrate (F + F group) in
      massive obstetric haemorrhage. In this retrospective study, we compared the
      medical charts (2004-2016) of 137 patients with <150 mg/dl fibrinogen treated
      with F + F (n = 47; after August 2009) or F (n = 56; before August 2009).
      Although fibrinogen concentrate was only administered in severe cases, the
      FFP/red blood cell concentrate (RCC) ratio was significantly lower in the F + F
      group than in the F group. A sub-group analysis of cases requiring >=18 RCC units
      showed that the F + F group received significantly less FFP than the F group
      (40.2 +/- 19.6 versus 53.4 +/- 18.5 units; P = 0.047) and showed significantly
      less pulmonary oedema (24.0% vs 57.1%; P < 0.05) in the absence of any
      significant differences in pre-transfusion coagulation, estimated blood loss, or
      RCC transfusion volume. Administration of fibrinogen concentrate increased the
      rate of fibrinogen supplementation five-fold and reduced FFP dosage, the FFP/RCC
      ratio, and the incidence of pulmonary oedema.

PMID- 28436464
TI  - Glucose-dependent regulation of pregnane X receptor is modulated by AMP-activated
      protein kinase.
AB  - Pregnane X receptor (PXR) is a xenobiotic receptor that regulates the
      detoxification and clearance of drugs and foreign compounds from the liver. There
      has been mounting evidence of crosstalk between the drug metabolism pathway and
      the energy metabolism pathway, but little is known about this cross-regulation.
      To further delineate the energy metabolism and drug metabolism crosstalk in this
      study, we exposed HepG2 cells to varying glucose concentrations. We observed that
      PXR activity was induced under high-glucose conditions. This finding is
      consistent with previous clinical reports of increased drug clearance in patients
      with untreated diabetes. We demonstrated that AMP-activated protein kinase (AMPK)
      modulates PXR transcriptional activity and that pharmacologically manipulated
      AMPK activation exhibits an inverse relation to PXR activity. Activation of AMPK
      was shown to downregulate PXR activity and, consistent with that, potentiate the
      response of cells to the drug. Taken together, our results delineate a hitherto
      unreported axis of regulation that involves the energy status of the cell, PXR
      regulation, and drug sensitivity.

PMID- 28436466
TI  - Genome-wide profiling of heritable and de novo STR variations.
AB  - Short tandem repeats (STRs) are highly variable elements that play a pivotal role
      in multiple genetic diseases, population genetics applications, and forensic
      casework. However, it has proven problematic to genotype STRs from high
      throughput sequencing data. Here, we describe HipSTR, a novel haplotype-based
      method for robustly genotyping and phasing STRs from Illumina sequencing data,
      and we report a genome-wide analysis and validation of de novo STR mutations.
      HipSTR is freely available at https://hipstr-tool.github.io/HipSTR.

PMID- 28436467
TI  - Prediction of intraventricular haemorrhage in preterm infants using time series
      analysis of blood pressure and respiratory signals.
AB  - Despite the decline in mortality rates of extremely preterm infants,
      intraventricular haemorrhage (IVH) remains common in survivors. The need for
      resuscitation and cardiorespiratory management, particularly within the first 24
      hours of life, are important factors in the incidence and timing of IVH.
      Variability analyses of heart rate and blood pressure data has demonstrated
      potential approaches to predictive monitoring. In this study, we investigated the
      early identification of infants at a high risk of developing IVH, using time
      series analysis of blood pressure and respiratory data. We also explore
      approaches to improving model performance, such as the inclusion of multiple
      variables and signal pre-processing to enhance the results from detrended
      fluctuation analysis. Of the models we evaluated, the highest area under receiver
      operator characteristic curve (5th, 95th percentile) achieved was 0.921 (0.82,
      1.00) by mean diastolic blood pressure and the long-term scaling exponent of
      pulse interval (PI alpha2), exhibiting a sensitivity of >90% at a specificity of
      75%. Following evaluation in a larger population, our approach may be useful in
      predictive monitoring to identify infants at high risk of developing IVH,
      offering caregivers more time to adjust intensive care treatment.

PMID- 28436468
TI  - Higher risk of colorectal cancer in patients with newly diagnosed diabetes
      mellitus before the age of colorectal cancer screening initiation.
AB  - Type 2 diabetes mellitus (T2DM) is associated with greater risk for colorectal
      cancer (CRC). The age of onset of T2DM is decreasing worldwide. An increased CRC
      risk in young T2DM patients could be relevant for the age at which to initiate
      CRC screening. We report on CRC risk in T2DM patients with attention to age of
      diagnosis. We used pharmacy data (from 1998 to 2010) from the PHARMO Database
      Network linked to the Eindhoven Cancer Registry. Multivariable time-dependent Cox
      regression analyses were conducted to calculate hazard ratios (HR) for developing
      CRC comparing T2DM with non-T2DM. During 2,599,925 years of follow-up, 394 CRC
      cases among 41,716 diabetes patients (mean age 64.0 yr, 48% men) and 1,939 CRC
      cases among 325,054 non-diabetic patients (mean age 51.2 yr, 46% men) were
      identified. Diabetes was associated with an increased CRC risk in both men and
      women (HR 1.3, 95% CI 1.2-1.5), particularly in the first 6 months after T2DM
      diagnosis and pronounced in the proximal colon. This risk was even higher in men
      younger than 55 years (HR 2.0, 95% CI 1.0-3.8). T2DM was associated with a time
      varying and subsite-specific increased CRC risk, which was even higher in men
      aged <55 years.

PMID- 28436470
TI  - New frontiers in translational control of the cancer genome.

PMID- 28436471
TI  - Tumour Suppressors: Following the clues of cancer-resistant tissues.

PMID- 28436469
TI  - A Novel Method to Evaluate Ribosomal Performance in Cell-Free Protein Synthesis
      Systems.
AB  - Cell-free protein synthesis (CFPS) systems were designed to produce proteins with
      a minimal set of purified components, thus offering the possibility to follow
      translation as well as protein folding. In order to characterize the performance
      of the ribosomes in such a system, it is crucial to separately quantify the two
      main components of productivity, namely the fraction of active ribosomes and the
      number of synthesizing cycles. Here, we provide a direct and highly reliable
      measure of ribosomal activity in any given CFPS system, introducing an enhanced
      arrest peptide variant. We observe an almost complete stalling of ribosomes that
      produce GFPem (~95%), as determined by common centrifugation techniques and
      fluorescence correlation spectroscopy (FCS). Moreover, we thoroughly study the
      effect of different ribosomal modifications independently on activity and number
      of synthesizing cycles. Finally, employing two-colour coincidence detection and
      two-colour colocalisation microscopy, we demonstrate real-time access to key
      productivity parameters with minimal sample consumption on a single ribosome
      level.

PMID- 28436472
TI  - Leukaemia: 'Gimme shelter'.

PMID- 28436473
TI  - Volumetric chemical imaging by stimulated Raman projection microscopy and
      tomography.
AB  - Volumetric imaging allows global understanding of three-dimensional (3D) complex
      systems. Light-sheet fluorescence microscopy and optical projection tomography
      have been reported to image 3D volumes with high resolutions and at high speeds.
      Such methods, however, usually rely on fluorescent labels for chemical targeting,
      which could perturb the biological functionality in living systems. We
      demonstrate Bessel-beam-based stimulated Raman projection (SRP) microscopy and
      tomography for label-free volumetric chemical imaging. Our SRP microscope enables
      fast quantitation of chemicals in a 3D volume through a two-dimensional lateral
      scan. Furthermore, combining SRP and sample rotation, we demonstrate the SRP
      tomography that can reconstruct the 3D distribution of chemical compositions with
      optical spatial resolution at a higher speed than the Gaussian-beam-based
      stimulated Raman scattering sectioning imaging can. We explore the potential of
      our SRP technology by mapping polymer particles in 3D volumes and lipid droplets
      in adipose cells.

PMID- 28436474
TI  - Interactions of AMTN, ODAM and SCPPPQ1 proteins of a specialized basal lamina
      that attaches epithelial cells to tooth mineral.
AB  - A specialized basal lamina (sBL) mediates adhesion of certain epithelial cells to
      the tooth. It is distinct because it does not contain collagens type IV and VII,
      is enriched in laminin-332, and includes three novel constituents called amelotin
      (AMTN), odontogenic ameloblast-associated (ODAM), and secretory calcium-binding
      phosphoprotein proline-glutamine rich 1 (SCPPPQ1). The objective of this study
      was to clarify the structural organization of the sBL. Fluorescence and
      immunogold labeling showed that the three proteins co-localize. Quantitative
      analysis of the relative position of gold particles on the sBL demonstrates that
      the distribution of ODAM is skewed towards the cell while that of AMTN and
      SCPPPQ1 tends towards the tooth surface. Bacterial two-hybrid analysis and co
      immunoprecipitation, gel filtration of purified proteins and transmission
      electron and atomic force microscopies highlight the propensity of AMTN, ODAM,
      and SCPPPQ1 to interact with and among themselves and form supramolecular
      aggregates. These data suggest that AMTN, ODAM and SCPPPQ1 participate in
      structuring an extracellular matrix with the distinctive capacity of attaching
      epithelial cells to mineralized surfaces. This unique feature is particularly
      relevant for the adhesion of gingival epithelial cells to the tooth surface,
      which forms a protective seal that is the first line of defense against bacterial
      invasion.

PMID- 28436475
TI  - A salient effect of density on the dynamics of nonaqueous electrolytes.
AB  - The mobility and solvation of lithium ions in electrolytes are crucial for the
      performance and safety of lithium ion batteries. It has been known that a single
      type of solvent cannot satisfy the requirements of both mobility and solvation
      simultaneously for electrolytes. Therefore, complex solvent mixtures have been
      used to optimize both properties. Here we present the effects of density on the
      dynamics and solvation of organic liquid electrolytes via extensive molecular
      dynamics simulations. Our study finds that a small variation in density can
      induce a significant effect on the mobility of electrolytes but does not
      influence the solvation structure of a lithium ion. It turns out that an
      adjustment of the density of electrolytes could provide a more effective way to
      enhance mobility than a control of the solvent mixture ratio of electrolytes. Our
      study reveals that the density change of electrolytes mainly affects the
      residence time of solvents in the first solvation shell of a lithium ion rather
      than the structural change of the solvation sheath. Finally, our results suggest
      an intriguing point for understanding and designing electrolytes of lithium ion
      batteries for better performance and safety.

PMID- 28436476
TI  - Multiplex lexical networks reveal patterns in early word acquisition in children.
AB  - Network models of language have provided a way of linking cognitive processes to
      language structure. However, current approaches focus only on one linguistic
      relationship at a time, missing the complex multi-relational nature of language.
      In this work, we overcome this limitation by modelling the mental lexicon of
      English-speaking toddlers as a multiplex lexical network, i.e. a multi-layered
      network where N = 529 words/nodes are connected according to four relationship:
      (i) free association, (ii) feature sharing, (iii) co-occurrence, and (iv)
      phonological similarity. We investigate the topology of the resulting multiplex
      and then proceed to evaluate single layers and the full multiplex structure on
      their ability to predict empirically observed age of acquisition data of English
      speaking toddlers. We find that the multiplex topology is an important proxy of
      the cognitive processes of acquisition, capable of capturing emergent lexicon
      structure. In fact, we show that the multiplex structure is fundamentally more
      powerful than individual layers in predicting the ordering with which words are
      acquired. Furthermore, multiplex analysis allows for a quantification of distinct
      phases of lexical acquisition in early learners: while initially all the
      multiplex layers contribute to word learning, after about month 23 free
      associations take the lead in driving word acquisition.

PMID- 28436477
TI  - Identification of risk factors in epidemiologic study based on ROC curve and
      network.
AB  - This article proposes a new non-parametric approach for identification of risk
      factors and their correlations in epidemiologic study, in which investigation
      data may have high variations because of individual differences or correlated
      risk factors. First, based on classification information of high or low disease
      incidence, we estimate Receptor Operating Characteristic (ROC) curve of each risk
      factor. Then, through the difference between ROC curve of each factor and
      diagonal, we evaluate and screen for the important risk factors. In addition,
      based on the difference of ROC curves corresponding to any pair of factors, we
      define a new type of correlation matrix to measure their correlations with
      disease, and then use this matrix as adjacency matrix to construct a network as a
      visualization tool for exploring the structure among factors, which can be used
      to direct further studies. Finally, these methods are applied to analysis on
      water pollutants and gastrointestinal tumor, and analysis on gene expression data
      in tumor and normal colon tissue samples.

PMID- 28436478
TI  - Tissue accumulation of microplastics in mice and biomarker responses suggest
      widespread health risks of exposure.
AB  - Microplastics (MPs) are a significant environmental health issue and increasingly
      greater source of concern. MPs have been detected in oceans, rivers, sediments,
      sewages, soil and even table salts. MPs exposure on marine organisms and humans
      has been documented, but information about the toxicity of MPs in mammal is
      limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs)
      particles with two diameters (5 MUm and 20 MUm) to investigate the tissue
      distribution, accumulation, and tissue-specific health risk of MPs in mice.
      Results indicated that MPs accumulated in liver, kidney and gut, with a tissue
      accumulation kinetics and distribution pattern that was strongly depended on the
      MPs particle size. In addition, analyses of multiple biochemical biomarkers and
      metabolomic profiles suggested that MPs exposure induced disturbance of energy
      and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers
      of neurotoxicity were also altered. Our results uncovered the distribution and
      accumulation of MPs across mice tissues and revealed significant alteration in
      several biomarkers that indicate potential toxicity from MPs exposure.
      Collectively, our data provided new evidence for the adverse consequences of MPs.

PMID- 28436479
TI  - Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy
      Treatments of Non-Small Cell Lung Cancer Patients.
AB  - The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a
      combination medication with adjuvant chemotherapy on postoperative early stage
      non-small cell lung cancer (NSCLC) patients. The 314 patients with completely
      resected stage IB, II or IIIA cancers were assigned into vinorelbine plus
      cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM
      (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary
      endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused
      mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising
      vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea
      (7.9%). The incidence of adverse events was significantly lower in the
      intervention group than in the control group (0.57% vs 4.02%, P = 0.037).
      Transient severe (grade 3 or 4) hematological toxic effects occurred less often
      (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to
      42.1 vs 46.2%) in the intervention compared to the control group during the 2nd
      chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial
      relief of symptoms in addition to a reduction of side-effects and adverse events
      caused by the NP/NC regimens.

PMID- 28436480
TI  - Dihydromyricetin Induces Apoptosis and Reverses Drug Resistance in Ovarian Cancer
      Cells by p53-mediated Downregulation of Survivin.
AB  - Ovarian cancer is one of the leading causes of death in gynecological
      malignancies, and the resistance to chemotherapeutic agents remains a major
      challenge to successful ovarian cancer chemotherapy. Dihydromyricetin (DHM), a
      natural flavonoid derived from Ampeopsis Grossdentata, has been widely applied in
      food industry and medicine for a long time. However, little is known about the
      effects of DHM on ovarian cancer and the underlying mechanisms. In this study, we
      demonstrated that DHM could effectively inhibit the proliferation of ovarian
      cancer cells and induce cell apoptosis. Survivin, an inhibitor of apoptosis
      (IAPs) family member, exhibited a decreased expression level after DHM treatment,
      which may be attributed to the activation of p53. Moreover, DHM markedly
      sensitized paclitaxel (PTX) and doxorubicin (DOX) resistant ovarian cancer cells
      to PTX and DOX by inhibiting survivin expression. Collectively, our findings
      highlight a previously undiscovered effect of DHM, which induces apoptosis and
      reverses multi-drug resistance against ovarian cancer cells through
      downregulation of survivin.

PMID- 28436481
TI  - Fusions of Tumor-derived Endothelial Cells with Dendritic Cells Induces Antitumor
      Immunity.
AB  - To explore dendritic cells/tumor-derived endothelial cells (DC/EC) fusion cells
      are potent stimulators of T cells to impact tumor progression. ECs were isolated
      from mice hepatoma cell line (H22) Xenograft, and dendritic cells were isolated
      from bone marrow of BALB/c mice, then the isolated ECs were cultured and detected
      the endothelial surface expression of CD105 by flow cytometry. The endothelial
      characteristics of ECs were detected by tube formation assay and Dil-Ac-LDL
      uptake assay. After the fusion with polyethylene glycol (PEG), we used DCs, ECs,
      DCs mixed ECs as the control groups, DC/EC fusion cells as the experimental
      group, Secretion of IFN-alpha and IFN-gamma was evaluated, T lymphocyte
      proliferation and cytotoxic T lymphocytes (CTL) were detected in vitro. In vivo,
      T lymphocyte induced by five groups was injected to detect the effect of tumor
      progression. Purified ECs (CD105+) took the function of endothelial cells, then
      successfully fused with DCs. The DC/EC fusion cells were functional in
      stimulating the proliferation of T cells, which produced IFN-alpha and IFN-gamma.
      In vivo, T cells stimulated by DC/EC fusion cells effectively repressed tumor
      growth. The fusion cells, which was capable of stimulating T cells, is
      indispensable for antitumor immunity.

PMID- 28436482
TI  - PathoSpotter-K: A computational tool for the automatic identification of
      glomerular lesions in histological images of kidneys.
AB  - PathoSpotter is a computational system designed to assist pathologists in
      teaching about and researching kidney diseases. PathoSpotter-K is the version
      that was developed to detect nephrological lesions in digital images of kidneys.
      Here, we present the results obtained using the first version of PathoSpotter-K,
      which uses classical image processing and pattern recognition methods to detect
      proliferative glomerular lesions with an accuracy of 88.3 +/- 3.6%. Such
      performance is only achieved by similar systems if they use images of cell in
      contexts that are much less complex than the glomerular structure. The results
      indicate that the approach can be applied to the development of systems designed
      to train pathology students and to assist pathologists in determining large-scale
      clinicopathological correlations in morphological research.

PMID- 28436483
TI  - iTRAQ-based proteomic analysis reveals key proteins affecting muscle growth and
      lipid deposition in pigs.
AB  - Growth rate and meat quality, two economically important traits in pigs, are
      controlled by multiple genes and biological pathways. In the present study, we
      performed a proteomic analysis of longissimus dorsi muscle from six-month-old
      pigs from two Chinese native mini-type breeds (TP and DSP) and two introduced
      western breeds (YY and LL) using isobaric tag for relative and absolute
      quantification (iTRAQ). In total, 4,815 peptides corresponding to 969 proteins
      were detected. Comparison of expression patterns between TP-DSP and YY-LL
      revealed 288 differentially expressed proteins (DEPs), of which 169 were up
      regulated and 119 were down-regulated. Functional annotation suggested that 28
      DEPs were related to muscle growth and 15 to lipid deposition. Protein
      interaction network predictions indicated that differences in muscle growth and
      muscle fibre between TP-DSP and YY-LL groups were regulated by ALDOC, ENO3, PGK1,
      PGK2, TNNT1, TNNT3, TPM1, TPM2, TPM3, MYL3, MYH4, and TNNC2, whereas differences
      in lipid deposition ability were regulated by LPL, APOA1, APOC3, ACADM, FABP3,
      ACADVL, ACAA2, ACAT1, HADH, and PECI. Twelve DEPs were analysed using parallel
      reaction monitoring to confirm the reliability of the iTRAQ analysis. Our
      findings provide new insights into key proteins involved in muscle growth and
      lipid deposition in the pig.

PMID- 28436484
TI  - How voluntary orienting of attention and alerting modulate costs of conflict
      processing.
AB  - There is evidence that pre-cued valid orienting of attention to competing
      information diminishes costs of brain processing of conflict. Still unclear,
      because scantily addressed by neuroimaging studies and mostly analyzed by means
      of behavioral indexing, it is whether conflict undergoes an equivalent modulation
      by tonic and pre-cued phasic alerting. Here, we investigated the functional
      relationships between attention orienting, alerting and executive systems using
      the Attention Network Test (ANT). Both reaction times (RTs) and ERPs were
      recorded. In line with previous literature, results showed that both RTs and a so
      called ERPs conflict negativity (CN), prominent at anterior scalp and indexing
      conflict processing, were positively modulated by a prior valid orienting of
      attention onto the location of conflicting stimuli. Indeed, in this condition
      both kinds of markers showed faster latencies, while CN also reached higher
      amplitude values than in both alerting conditions, and, in turn, in pre-cued
      phasic alerting than in uncued tonic alerting. Moreover, while CN was larger over
      the right hemisphere independent of functional conditions, it was strongly
      modulated by the latter over the left hemisphere. Our ERP findings support the
      views of conflict modulation by both orienting and phasic alerting and of a
      functional integration between attentional brain networks.

PMID- 28436485
TI  - Dyslipidaemia: Hypertriglyceridaemia caused by GPIHBP1 autoantibodies.

PMID- 28436488
TI  - Pathology, imaging, and treatment of cardiac tumours.
AB  - Cardiac tumours are a rare, but often devastating, clinical diagnosis. They
      encompass a broad set of lesions that include both neoplastic and non-neoplastic
      conditions. Cardiac tumours are often diagnosed incidentally during work-up for
      other conditions, or during ultrasound, CT, or MRI scans for unusual or
      nonspecific symptoms. In the past decade, important changes have been made in the
      nomenclature and the recommendations for diagnosis of cardiac tumours, as
      highlighted by the WHO's 2015 revision of the classification of cardiac tumours.
      Moreover, important advances in molecular genetics and therapeutics offer new
      approaches for the diagnosis and treatment of affected patients. In this Review,
      we provide an overview of the clinical, pathological, and imaging characteristics
      of all types of cardiac masses, including both benign and malignant primary
      cardiac neoplasms.

PMID- 28436487
TI  - Redefining the identity of cardiac fibroblasts.
AB  - Cardiac fibroblasts deposit and maintain extracellular matrix during
      organogenesis and under physiological conditions. In the adult heart, activated
      cardiac fibroblasts also participate in the healing response after acute
      myocardial infarction and during chronic disease states characterized by
      augmented interstitial fibrosis and ventricular remodelling. However, delineation
      of the characteristics, plasticity, and origins of cardiac fibroblasts is an area
      of ongoing investigation and controversy. A set of genetic mouse models has been
      developed that specifically addresses the nature of these cells, in terms of both
      their origins and their response during cardiac disease and ventricular
      remodelling. As our understanding of cardiac fibroblasts becomes more defined and
      refined, so does the potential to develop new therapeutic strategies to control
      fibrosis and adverse ventricular remodelling.

PMID- 28436489
TI  - Hypertension: Very low achieved SBP increases risk of cardiovascular death.

PMID- 28436490
TI  - Solitonic Josephson-based meminductive systems.
AB  - Memristors, memcapacitors, and meminductors represent an innovative generation of
      circuit elements whose properties depend on the state and history of the system.
      The hysteretic behavior of one of their constituent variables, is their
      distinctive fingerprint. This feature endows them with the ability to store and
      process information on the same physical location, a property that is expected to
      benefit many applications ranging from unconventional computing to adaptive
      electronics to robotics. Therefore, it is important to find appropriate memory
      elements that combine a wide range of memory states, long memory retention times,
      and protection against unavoidable noise. Although several physical systems
      belong to the general class of memelements, few of them combine these important
      physical features in a single component. Here, we demonstrate theoretically a
      superconducting memory based on solitonic long Josephson junctions. Moreover,
      since solitons are at the core of its operation, this system provides an
      intrinsic topological protection against external perturbations. We show that the
      Josephson critical current behaves hysteretically as an external magnetic field
      is properly swept. Accordingly, long Josephson junctions can be used as multi
      state memories, with a controllable number of available states, and in other
      emerging areas such as memcomputing, i.e., computing directly in/by the memory.

PMID- 28436486
TI  - Muscle wasting and cachexia in heart failure: mechanisms and therapies.
AB  - Body wasting is a serious complication that affects a large proportion of
      patients with heart failure. Muscle wasting, also known as sarcopenia, is the
      loss of muscle mass and strength, whereas cachexia describes loss of weight.
      After reaching guideline-recommended doses of heart failure therapies, the most
      promising approach to treating body wasting seems to be combined therapy that
      includes exercise, nutritional counselling, and drug treatment. Nutritional
      considerations include avoiding excessive salt and fluid intake, and
      replenishment of deficiencies in trace elements. Administration of omega-3
      polyunsaturated fatty acids is beneficial in selected patients. High-calorific
      nutritional supplements can also be useful. The prescription of aerobic exercise
      training that provokes mild or moderate breathlessness has good scientific
      support. Drugs with potential benefit in the treatment of body wasting that have
      been tested in clinical studies in patients with heart failure include
      testosterone, ghrelin, recombinant human growth hormone, essential amino acids,
      and beta2-adrenergic receptor agonists. In this Review, we summarize the
      pathophysiological mechanisms of muscle wasting and cachexia in heart failure,
      and highlight the potential treatment strategies. We aim to provide clinicians
      with the relevant information on body wasting to understand and treat these
      conditions in patients with heart failure.

PMID- 28436491
TI  - Extratropical Forcing Triggered the 2015 Madden-Julian Oscillation-El Nino Event.
AB  - In this paper, we report the triggering effect of extratropical perturbation on
      the onset of an atypical Madden-Julian Oscillation (MJO) and onset of the 2015-16
      El Nino in March 2015. The MJO exhibited several unique characteristics: the
      effect of extratropical forcing, atypical genesis location and timing in the
      equatorial western Pacific, and the extremity of amplitudes in many aspects. The
      southward-penetrating northerly associated with the extratropical disturbances in
      the extratropical western North Pacific contributed to triggering the deep
      convection and westerly wind burst (WWB) and onset of the MJO over the
      anomalously warm tropical western Pacific in early March. The persisting strong
      WWB forced downwelling Kelvin wave-like oceanic perturbation that propagated
      eastward and led to the onset of the 2015-16 El Nino. The proposed novel
      extratropical forcing mechanism explaining the unique extratropics-MJO-El Nino
      association, based on both data diagnostics and numerical experiments, warrants
      further attention for a more detailed understanding of the onset of the MJO and
      its potential effect on El Nino.

PMID- 28436492
TI  - A multi-crystal method for extracting obscured crystallographic states from
      conventionally uninterpretable electron density.
AB  - In macromolecular crystallography, the rigorous detection of changed states (for
      example, ligand binding) is difficult unless signal is strong. Ambiguous ('weak'
      or 'noisy') density is experimentally common, since molecular states are
      generally only fractionally present in the crystal. Existing methodologies focus
      on generating maximally accurate maps whereby minor states become discernible; in
      practice, such map interpretation is disappointingly subjective, time-consuming
      and methodologically unsound. Here we report the PanDDA method, which
      automatically reveals clear electron density for the changed state-even from
      inaccurate maps-by subtracting a proportion of the confounding 'ground state';
      changed states are objectively identified from statistical analysis of density
      distributions. The method is completely general, implying new best practice for
      all changed-state studies, including the routine collection of multiple ground
      state crystals. More generally, these results demonstrate: the incompleteness of
      atomic models; that single data sets contain insufficient information to model
      them fully; and that accuracy requires further map-deconvolution approaches.

PMID- 28436493
TI  - An attenuated Mycobacterium tuberculosis clinical strain with a defect in ESX-1
      secretion induces minimal host immune responses and pathology.
AB  - Although Mycobacterium tuberculosis (M.tb) DK9897 is an attenuated strain, it was
      isolated from a patient with extrapulmonary tuberculosis and vaccination with a
      subunit vaccine (H56) induced poor protection against it. Both attenuation and
      lack of protection are because M.tb DK9897 cannot secrete the EsxA virulence
      factor nor induce a host response against it. Genome sequencing identified a
      frameshift mutation in the eccCa1 gene. Since the encoded EccCa1 protein provides
      energy for ESX-1 secretion, it suggested a defect in the ESX-1 type VII secretion
      system. Genetic complementation with a plasmid carrying the M.tb H37Rv sequence
      of eccCa1-eccCb1-pe35 re-established EsxA secretion, host specific EsxA T-cell
      responses, and increased strain virulence. The ESX-1 secretion defect prevents
      several virulence factors from being functional during infection and therefore
      attenuates M.tb. It precludes specific T-cell responses against strong antigens
      and we found very little in vivo cytokine production, gross pathology or
      granuloma formation in lungs from M.tb DK9897 infected animals. This coincides
      with M.tb DK9897 being unable to disrupt the phagosome membrane and make contact
      to the cytosol.

PMID- 28436495
TI  - Electrochemistry-mass spectrometry for mechanism study of oxygen reduction at
      water/oil interface.
AB  - Electrochemistry methods have been widely employed in the development of
      renewable energy, and involved in various processes, e.g. water splitting and
      oxygen reduction. Remarkable progress notwithstanding, there are still many
      challenges in further optimization of catalysts to achieve high performance. For
      this purpose, an in-depth understanding of reaction mechanism is needed. In this
      study, an electrochemistry-mass spectrometry method based on a Y-shaped dual
      channel microchip as electrochemical cell and ionization device was demonstrated.
      Combined solutions of aqueous phase and oil phase were introduced into mass
      spectrometer directly when electrochemical reactions were happening to study the
      reduction of oxygen by decamethylferrocene or tetrathiafulvalene under the
      catalysis of a metal-free porphyrin, tetraphenylporphyrin, at water/1,2
      dichloroethane interfaces. Monoprotonated and diprotonated tetraphenylporphyrin
      were detected by mass spectrometer, confirming the previously proposed mechanism
      of the oxygen reduction reaction. This work offers a new approach to study
      electrochemical reactions at liquid-liquid interface.

PMID- 28436494
TI  - Platinum-nickel alloy excavated nano-multipods with hexagonal close-packed
      structure and superior activity towards hydrogen evolution reaction.
AB  - Crystal phase regulations may endow materials with enhanced or new
      functionalities. However, syntheses of noble metal-based allomorphic
      nanomaterials are extremely difficult, and only a few successful examples have
      been found. Herein, we report the discovery of hexagonal close-packed Pt-Ni
      alloy, despite the fact that Pt-Ni alloys are typically crystallized in face
      centred cubic structures. The hexagonal close-packed Pt-Ni alloy nano-multipods
      are synthesized via a facile one-pot solvothermal route, where the branches of
      nano-multipods take the shape of excavated hexagonal prisms assembled by six
      nanosheets of 2.5 nm thickness. The hexagonal close-packed Pt-Ni excavated nano
      multipods exhibit superior catalytic property towards the hydrogen evolution
      reaction in alkaline electrolyte. The overpotential is only 65 mV versus
      reversible hydrogen electrode at a current density of 10 mA cm-2, and the mass
      current density reaches 3.03 mA MUgPt-1 at -70 mV versus reversible hydrogen
      electrode, which outperforms currently reported catalysts to the best of our
      knowledge.

PMID- 28436496
TI  - Effect of anthraquinone-2,6-disulfonate on the photolysis of 2,4,4'
      tribromophenylphenyl ether.
AB  - In this study, we have investigated the photolysis of 2,4,4'-tribromophenylphenyl
      ether (BDE-28) in Triton X-100 (TX-100) solutions, and discussed the effect of
      anthraquinone-2,6-disulfonate (AQDS) on the photolysis of BDE-28. The effect of
      TX-100 on the photolysis of BDE-28 was mainly related to the concentration of TX
      100. The fastest photolysis of BDE-28 was at 500 mg L-1 of the TX-100 solution,
      and the corresponding photolysis rate constant was 0.12 min-1. The direct
      photolysis rate of BDE-28 decreased from 0.17 min-1 to 0.08 min-1 and 0.12 min-1
      when NaN3 and isopropanol were added, respectively. The effect of AQDS on the
      photolysis of BDE-28 was also mainly related to the concentration of AQDS. When
      the concentration of AQDS was 0.6 MUM, it has a slight influence in promoting the
      photodegradation of BDE-28; as the AQDS concentrations increased, the suppressing
      effect was more obvious. AQDS can inhibit the photolysis of BDE-28. Photolysis
      kinetics and quenching reactions illustrated that BDE-28 can produce a
      photosensitization reaction in TX-100 solutions, and the effects of AQDS on the
      photolysis of BDE-28 were mainly dominated by inhibition. In addition to its
      light shielding effect, AQDS can also combine with BDE-28 and anti-oxidation to
      inhibit the photolysis of BDE-28. We found that the degradation pathway of BDE-28
      was mainly based on de-bromination, and the ions at para positions were
      preferentially debrominated.

PMID- 28436497
TI  - Metal ion binding by laterally non-symmetric macrobicyclic oxa-aza cryptands.
AB  - Macrobicyclic cryptands incorporating amine groups along with oxygen donors that
      are laterally non-symmetric constitute an important class of organic compounds.
      These molecules can form inclusion complexes with different transition and main
      group metal ions. It is also possible to modify the binding characteristics of
      these compounds through attachment of different groups. Some of these metal
      complexes can be useful homogeneous catalysts in different organic
      transformations. If there are chiral centers present in the cryptands, they can
      be useful in asymmetric syntheses. The three secondary amine groups present in
      the bridges can be partially or completely derivatized with different
      fluorophores for fluorescence signaling of transition, inner-transition and heavy
      metal ions. It is also possible to sequentially attach different fluorophores to
      study single- as well as multi-step Forster resonance energy transfer. Different
      donor/acceptor groups can be attached to study second and third order optical
      nonlinearity. The present article describes several aspects of the chemistry of
      laterally non-symmetric cryptands and provides future directions for research in
      this area.

PMID- 28436499
TI  - White light emission with tuneable colour temperature and high colour rendering
      index from CdS/Si multi-interface nanoheterojunctions.
AB  - CdS/Si multi-interface nanoheterojunctions (CdS/Si-NPA) were fabricated by
      depositing CdS nanocrystallites (nc-CdS) on silicon nanoporous pillar arrays (Si
      NPA) by chemical bath deposition. White electroluminescence (EL) with a high
      colour rendering index from a prototypical light emitting diode based on CdS/Si
      NPA has been reported, which does not need complex colour mixing or conversion
      techniques. The white EL can be composed into three primary colours, which
      include blue emissions from the Si-NPA, the green emissions from the bandgap
      emission of nc-CdS and red emissions from the defects in the nc-CdS. Through the
      annealing treatment, the chromaticity coordinate and correlated colour
      temperature can be tuned. This indicates that CdS/Si-NPA is a potential candidate
      in the one-chip white LEDs.

PMID- 28436498
TI  - Integrative meta-modeling identifies endocytic vesicles, late endosome and the
      nucleus as the cellular compartments primarily directing RTK signaling.
AB  - Recently, intracellular receptor signaling has been identified as a key component
      mediating cell responses for various receptor tyrosine kinases (RTKs). However,
      the extent each endocytic compartment (endocytic vesicle, early endosome,
      recycling endosome, late endosome, lysosome and nucleus) contributes to receptor
      signaling has not been quantified. Furthermore, our understanding of endocytosis
      and receptor signaling is complicated by cell- or receptor-specific endocytosis
      mechanisms. Therefore, towards understanding the differential endocytic
      compartment signaling roles, and identifying how to achieve signal transduction
      control for RTKs, we delineate how endocytosis regulates RTK signaling. We
      achieve this via a meta-analysis across eight RTKs, integrating computational
      modeling with experimentally derived cell (compartment volume, trafficking
      kinetics and pH) and ligand-receptor (ligand/receptor concentration and
      interaction kinetics) physiology. Our simulations predict the abundance of
      signaling from eight RTKs, identifying the following hierarchy in RTK signaling:
      PDGFRbeta > IGFR1 > EGFR > PDGFRalpha > VEGFR1 > VEGFR2 > Tie2 > FGFR1. We find
      that endocytic vesicles are the primary cell signaling compartment; over 43% of
      total receptor signaling occurs within the endocytic vesicle compartment for
      these eight RTKs. Mechanistically, we found that high RTK signaling within
      endocytic vesicles may be attributed to their low volume (5.3 * 10-19 L) which
      facilitates an enriched ligand concentration (3.2 MUM per ligand molecule within
      the endocytic vesicle). Under the analyzed physiological conditions, we
      identified extracellular ligand concentration as the most sensitive parameter to
      change; hence the most significant one to modify when regulating absolute
      compartment signaling. We also found that the late endosome and nucleus
      compartments are important contributors to receptor signaling, where 26% and 18%,
      respectively, of average receptor signaling occurs across the eight RTKs.
      Conversely, we found very low membrane-based receptor signaling, exhibiting <1%
      of the total receptor signaling for these eight RTKs. Moreover, we found that
      nuclear translocation, mechanistically, requires late endosomal transport; when
      we blocked receptor trafficking from late endosomes to the nucleus we found a 57%
      reduction in nuclear translocation. In summary, our research has elucidated the
      significance of endocytic vesicles, late endosomes and the nucleus in RTK signal
      propagation.

PMID- 28436500
TI  - Black phosphorus nanostructures: recent advances in hybridization, doping and
      functionalization.
AB  - Owing to its high charge-carrier mobility, tunable direct-bandgap and unique in
      plane anisotropic structure, black phosphorus (BP), a rising star of post
      graphene two-dimensional (2D) nanomaterials, has been intensively investigated
      since early 2014. To explore its full potential and push the limits, research
      into BP-based novel functional nanostructures (i.e., nanomaterials and
      nanodevices) by means of hybridization, doping, and functionalization is rapidly
      expanding. Indeed, the cutting-edge developments and applications of BP
      nanostructures have had a significant impact on a wide range of research areas,
      including field effect transistors, diodes, photodetectors, biomedicine, sodium
      ion batteries, photocatalysis, electrocatalysis, memory devices, and more. This
      tutorial review summarizes the recent advances of BP nanostructures and outlines
      the future challenges and opportunities.

PMID- 28436501
TI  - Bis-ZnII salphen complexes bearing pyridyl functionalized ligands for efficient
      organic light-emitting diodes (OLEDs).
AB  - Inspired by the emissive features of ZnII complexes based on bis-Schiff base
      ligands, bis-ZnII salphen complexes bearing pyridyl functionalized ligands have
      been successfully synthesized. Their photophysical features, electrochemical
      behavior and electroluminescent (EL) properties have been investigated in detail.
      The functionalized bis-ZnII salphen complexes can exhibit high thermal stability
      up to 417  degrees C, and their photoluminescence (PL) spectra show a maximal
      emission wavelength peak at ca. 565 nm both in solution and PMMA doped films. The
      PL investigation of the neat films for these functionalized bis-ZnII salphen
      complexes indicated that the pyridyl functionalized ligands can effectively
      reduce the degree of molecular aggregation to enhance their emission intensity.
      Taking advantage of the charge carrier injection/transporting ability of the
      pyridyl functionalized ligands and their dendritic design, the optimized EL
      devices fabricated by a simple solution-processing method can achieve a peak
      luminance (Lmax) of 3589 cd m-2, a maximal external quantum efficiency (etaext)
      of 1.46%, a maximal current efficiency (etaL) of 4.1 cd A-1 and a maximal power
      efficiency (etap) of 3.8 lm W-1. These results should afford important
      instructions for exploiting high performance fluorescent emitters based on
      dinuclear ZnII complexes.

PMID- 28436502
TI  - Arsenolipids exert less toxicity in a human neuron astrocyte co-culture as
      compared to the respective monocultures.
AB  - Arsenic-containing hydrocarbons (AsHCs), natural products found in seafood, have
      recently been shown to exert toxic effects in human neurons. In this study we
      assessed the toxicity of three AsHCs in cultured human astrocytes. Due to the
      high cellular accessibility and substantial toxicity observed astrocytes were
      identified as further potential brain target cells for arsenolipids. Thereby, the
      AsHCs exerted a 5-19-fold higher cytotoxicity in astrocytes as compared to
      arsenite. Next we compared the toxicity of the arsenicals in a co-culture model
      of the respective human astrocytes and neurons. Notably the AsHCs did not show
      any substantial toxic effects in the co-culture, while arsenite did. The arsenic
      accessibility studies indicated that in the co-culture astrocytes protect neurons
      against cellular arsenic accumulation especially after incubation with
      arsenolipids. In summary, these data underline the importance of the glial-neuron
      interaction when assessing the in vitro neurotoxicity of new unclassified metal
      species.

PMID- 28436503
TI  - Stimuli-responsive hydrogel microfibers with controlled anisotropic shrinkage and
      cross-sectional geometries.
AB  - Stimuli-responsive microfibers are fabricated by extruding mixed solutions of
      poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) and sodium alginate (Na
      alginate) using a microfluidic spinning system. The fabricated microfibers shrink
      and swell with temperature and/or pH. By controlling the extruded laminar flow,
      microfibers capable of anisotropic shrinkage are fabricated. Cross-sectional
      microscale geometries of microfibers, including double layering and hollowness,
      are successfully controlled by patterning the laminar flow during microfiber
      formation, resulting in hydrogels capable of folding/unfolding motions and fluid
      pumping. In addition, macroscopic 3D-bundle structures are assembled with these
      microfibers. We believe that our microfibers can be applied to various
      applications such as soft actuators, soft robots, and micropumps.

PMID- 28436504
TI  - Designing CO2-resistant oxygen-selective mixed ionic-electronic conducting
      membranes: guidelines, recent advances, and forward directions.
AB  - CO2 resistance is an enabling property for the wide-scale implementation of
      oxygen-selective mixed ionic-electronic conducting (MIEC) membranes in clean
      energy technologies, i.e., oxyfuel combustion, clean coal energy delivery, and
      catalytic membrane reactors for greener chemical synthesis. The significant rise
      in the number of studies over the past decade and the major progress in CO2
      resistant MIEC materials warrant systematic guidelines on this topic. To this
      end, this review features the pertaining aspects in addition to the recent status
      and advances of the two most promising membrane materials, perovskite and
      fluorite-based dual-phase materials. We explain how to quantify and design CO2
      resistant membranes using the Lewis acid-base reaction concept and thermodynamics
      perspective and highlight the relevant characterization techniques. For
      perovskite materials, a trade-off generally exists between CO2 resistance and O2
      permeability. Fluorite materials, despite their inherent CO2 resistance,
      typically have low O2 permeability but this can be improved via different
      approaches including thin film technology and the recently developed minimum
      internal electronic short-circuit second phase and external electronic short
      circuit decoration. We then elaborate the two main future directions that are
      centralized around the development of new oxide compositions capable of featuring
      simultaneously high CO2 resistance and O2 permeability and the exploitation of
      phase reactions to create a new conductive phase along the grain boundaries of
      dual-phase materials. The final part of the review discusses various
      complimentary characterization techniques and the relevant studies that can
      provide insights into the degradation mechanism of oxide-based materials upon
      exposure to CO2.

PMID- 28436505
TI  - Well-defined functional mesoporous silica/polymer hybrids prepared by an ICAR
      ATRP technique integrated with bio-inspired polydopamine chemistry for lithium
      isotope separation.
AB  - Mesoporous silica/polymer hybrids with well-preserved mesoporosity were prepared
      by integrating the initiators for continuous activator regeneration (ICAR) atom
      transfer radical polymerization (ATRP) technique with the bio-inspired
      polydopamine (PDA) chemistry. By manipulating the auto-oxidative polymerization
      of dopamine, uniform PDA layers were deposited on the surfaces and pore walls of
      ordered mesoporous silicas (OMSs), thereby promoting the immobilization of ATRP
      initiators. Poly(glycidyl methacrylate) (PGMA) brushes were then grown from the
      OMSs by using the ICAR ATRP technique. The evolution of the mesoporous
      silica/polymer hybrids during synthesis, in terms of morphology, structure,
      surface and porous properties, was detailed. And, parameters influencing the
      controlled growth of polymer chains in the ICAR ATRP system were studied. Taking
      advantage of the abundant epoxy groups in the PGMA platform, post
      functionalization of the mesoporous silica/polymer hybrids by the covalent
      attachment of macrocyclic ligands for the adsorptive separation of lithium
      isotopes was realized. Adsorption behavior of the functionalized hybrids toward
      lithium ions was fully investigated, highlighting the good selectivity, and
      effects of temperature, solvent and counter ions. The ability for lithium isotope
      separation was evaluated. A higher separation factor could be obtained in systems
      with softer counter anions and lower polarity solvents. More importantly, due to
      the versatility of the ICAR ATRP technique, combined with the non-surface
      specific PDA chemistry, the methodology established in this work would provide
      new opportunities for the preparation of advanced organic-inorganic porous
      hybrids for broadened applications.

PMID- 28436506
TI  - Electrostatic interactions between ions near Thomas-Fermi substrates and the
      surface energy of ionic crystals at imperfect metals.
AB  - The electrostatic interaction between two charged particles is strongly modified
      in the vicinity of a metal. This situation is usually accounted for by the
      celebrated image charges approach, which was further extended to account for the
      electronic screening properties of the metal at the level of the Thomas-Fermi
      description. In this paper we build upon a previous approach [M. A. Vorotyntsev
      and A. A. Kornyshev, Zh. Eksp. Teor. Fiz., 1980, 78(3), 1008-1019] and successive
      works to calculate the 1-body and 2-body electrostatic energy of ions near a
      metal in terms of the Thomas-Fermi screening length. We propose workable
      approximations suitable for molecular simulations of ionic systems close to
      metallic walls. Furthermore, we use this framework to calculate analytically the
      electrostatic contribution to the surface energy of a one dimensional crystal at
      a metallic wall and its dependence on the Thomas-Fermi screening length. These
      calculations provide a simple interpretation for the surface energy in terms of
      image charges, which allows for an estimation of the interfacial properties in
      more complex situations of a disordered ionic liquid close to a metal surface.
      The counter-intuitive outcome is that electronic screening, as characterized by a
      molecular Thomas-Fermi length lTF, profoundly affects the wetting of ionic
      systems close to a metal, in line with the recent experimental observation of
      capillary freezing of ionic liquids in metallic confinement.

PMID- 28436507
TI  - Enhanced photogenerated carrier separation in CdS quantum dot sensitized
      ZnFe2O4/ZnIn2S4 nanosheet stereoscopic films for exceptional visible light
      photocatalytic H2 evolution performance.
AB  - CdS quantum dot sensitized ZnFe2O4/ZnIn2S4 nanosheet stereoscopic films were
      synthesized through two sequential solvothermal processes and the ionic layer
      adsorption-reaction method. The hydrophilic ZnIn2S4 nanosheet stereoscopic film
      was pre-prepared to act as a suitable host material, and then ZnFe2O4
      nanoparticles and CdS quantum dots were uniformly decorated on the surface of the
      ZnIn2S4 nanosheet stereoscopic film to form a ternary heterostructure
      stereoscopic film. The band structure difference in the ternary heterostructure
      can promote the spatial separation and transport efficiency of photogenerated
      charge carriers. Meanwhile, the composite stereoscopic film has significant
      structural advantages and can provide a large amount of reaction active sites and
      outstanding visible light utilization. The superhydrophilic surface contributes
      to interface contact of catalyst/solution and gas detachment. These positive
      factors led to a significantly enhanced photocatalytic H2 evolution activity of
      the CdS/ZnFe2O4/ZnIn2S4 ternary heterostructure film in comparison with the
      pristine ZnIn2S4 and binary heterostructure film photocatalysts. The optimized
      CdS/ZnFe2O4/ZnIn2S4 ternary heterostructure film demonstrates the highest H2
      production rate of 79.0 MUmol h-1, which surpasses that of ZnIn2S4 by more than
      3.2 times. This synthesis strategy can be applicable for the facile synthesis of
      other visible-light-driven composite film catalysts.

PMID- 28436508
TI  - Purification, characterization and bioactivities of polysaccharides from
      Pleurotus ferulae.
AB  - Pleurotus ferulae is an edible mushroom and has been used in Uygur medicine for a
      long time. In this study, we purified polysaccharides from P. ferulae (PFPS) and
      investigated its structural characteristics. We obtained a homogeneous PFPS with
      a molecular weight of around 1600 kDa and prominent characteristic polysaccharide
      groups, which mainly contained glucose (97%), followed by mannose and galactose
      (3%). Both 1H and 13C NMR spectra indicated that PFPS contained both alpha- and
      beta-anomeric configurations. Atomic force microscopy and Congo red-staining data
      further suggested that PFPS belonged to a linear branched structure that existed
      in flexible single chains at low concentrations and could form aggregates such as
      a triple-helical structure at high concentrations. Moreover, PFPS promoted the
      maturation of dendritic cells through a TLR4 mediated signaling pathway, which is
      characterized by the increased expressions of CD40, CD86, IL-12 and TNF-alpha and
      the decreased endocytosis. The results suggest that PFPS has immunoregulatory
      activities.

PMID- 28436509
TI  - Covering the optical spectrum through collective rare-earth doping of NaGdF4
      nanoparticles: 806 and 980 nm excitation routes.
AB  - Today, at the frontier of biomedical research, the need has been clearly
      established for integrating disease detection and therapeutic function in one
      single theranostic system. Light-emitting nanoparticles are being intensively
      investigated to fulfil this demand, by continuously developing nanoparticle
      systems simultaneously emitting in both the UV/visible (light-triggered release
      and activation of drugs) and the near-infrared (imaging and tracking) spectral
      regions. In this work, rare-earth (RE) doped nanoparticles (RENPs) were
      synthesized via a thermal decomposition process and spectroscopically
      investigated as potential candidates as all-in-one optical imaging, diagnostic
      and therapeutic agents. These core/shell/shell nanoparticles
      (NaGdF4:Er3+,Ho3+,Yb3+/NaGdF4:Nd3+,Yb3+/NaGdF4) are optically excited by heating
      free 806 nm light that, aside from minimizing the local thermal load, also allows
      to obtain a deeper sub-tissue penetration with respect to the still widely used
      980 nm light. Moreover, these water-dispersed nanoplatforms offer interesting
      assets as triggers/probes for biomedical applications, by virtue of a plethora of
      emission bands (spanning the 380-1600 nm range). Our results pave the way to use
      these RENPs for UV/visible-triggered photodynamic therapy/drug release, while
      simultaneously tracking the nanoparticle biodistribution and monitoring their
      therapeutic action through the near-infrared signal that overlaps with biological
      transparency windows.

PMID- 28436510
TI  - Unique structural properties of DNA interstrand cross-links formed by a new
      antitumor dinuclear Pt(ii) complex.
AB  - The DNA interstrand cross-links of the antitumor drug {[cis-Pt(NH3)2Cl]2(4,4'
      methylenedianiline)}2+ (1) play a prevalent role in its antitumor effects.
      Complex 1 forms DNA long-range interstrand cross-links uniquely in the 3'-3'
      direction. Conformational distortions induced by these interstrand cross-links in
      DNA represent a potential structural motif for recognition by high-mobility-group
      proteins.

PMID- 28436511
TI  - Self-template synthesis of CdS/NiSx heterostructured nanohybrids for efficient
      photocatalytic hydrogen evolution.
AB  - Photocatalytic hydrogen (H2) evolution from water splitting is attracting
      enormous interest due to the possibility of converting solar energy into green
      chemical energy. The construction of highly efficient and stable photocatalysts
      is of importance and necessary for the development of photocatalytic water
      splitting technology. In this study, we have developed a self-template synthetic
      strategy for the preparation of heterostructured nanohybrids composed of
      ultrasmall CdS and NiSx nanoparticles by using Cd(ii)-Ni(ii)-(4,4'-bipyridine)
      coordination polymers as the precursor and template. The CdS/NiSx nanohybrids are
      comprised of integrated CdS and NiSx nanoclusters in a heterostructure which
      function as highly efficient visible-light-driven H2 evolution photocatalysts.
      The enhanced photocatalytic performance could be attributed to the formation of
      hetero-junctions between CdS and NiSx nanoparticles inside the nanohybrids which
      could effectively improve the separation efficiency of photogenerated electrons
      and holes, and thus enhance the photocatalytic activity. This work can provide a
      new insight into the design and fabrication of other heterostructured
      photocatalysts for solar-driven water splitting or other photocatalytic
      applications.

PMID- 28436512
TI  - Exploring the orthorhombic-tetragonal phase transition in CH3NH3PbI3: the role of
      atom kinetics.
AB  - Methylammonium lead tri-iodide is a polymorphic material with two temperature
      induced phase transitions at 165 K and 327 K, accompanied by an orthorhombic-to
      tetragonal and a tetragonal-to-cubic lattice modification. Understanding the
      origins of these transitions as well as their implications on the crystal
      structure of the material is fundamental for its technological optimization.
      Here, we use the density functional theory along with ab initio molecular
      dynamics to study the low-temperature phase transition of CH3NH3PbI3. Considering
      two kinetically robust models for the orthorhombic and the tetragonal phase, we
      show that the vibrational features of the material can be strongly affected by
      the orientations of the methylammonium ions. We argue that the orthorhombic
      tetragonal transition is characterized by a partial rearrangement of the organic
      cations that locally relaxes the stress induced by the thermal movement of atoms.
      We finally propose a macroscopic model for the tetragonal phase that consists of
      rotated noncentrosymmetric domains, where the methylammonium ions are quasi-two
      dimensionally confined around the a-b crystallographic plane.

PMID- 28436513
TI  - Self-inverted reciprocation of an oil droplet on a surfactant solution.
AB  - Self-motion of an oil droplet was investigated on a sodium dodecyl sulfate (SDS)
      aqueous phase. With an increase in the concentration of SDS, the nature of self
      motion of a butyl salicylate (BS) droplet as the oil droplet was changed, i.e.,
      no motion, reciprocation with a small amplitude, and reciprocation with a large
      amplitude, which was a value close to the half-length of the chamber. The
      interfacial tension, contact angle, and convective flow around the droplet were
      measured to clarify the driving force of reciprocation. The mechanisms of two
      types of reciprocation and mode-change were discussed in terms of the adsorption
      of SDS molecules at the BS/water interface and the dissolution of a mixture of BS
      and SDS into the bulk phase, the convective flow, and the Young's equation. The
      features of reciprocation and mode-change depending on the concentration of SDS
      were qualitatively reproduced by numerical calculation based on an equation of
      motion and the kinetics of SDS and BS at the air/aqueous interface.

PMID- 28436514
TI  - CpG loaded MoS2 nanosheets as multifunctional agents for photothermal enhanced
      cancer immunotherapy.
AB  - Single or few-layered MoS2 nanosheets, as a novel class of 2D nanomaterials, have
      received tremendous attention due to their fantastic physical and chemical
      properties. Here, we fabricated MoS2-PEG-CpG with a small and uniform size as a
      multifunctional platform for photothermal enhanced immunotherapy. MoS2 nanosheets
      were fabricated by chemical exfoliation and further probe sonication. To realize
      MoS2-based adjuvant delivery, MoS2 nanosheets were functionalized with cytosine
      phosphate-guanine (CpG) and polyethylene glycol (PEG) to form MoS2-PEG-CpG
      nanoconjugates. As an efficient nanocarrier with excellent near infrared-light
      (NIR) absorbing performance, MoS2-PEG-CpG significantly promotes CpG
      intracellular accumulation and the effect can be further enhanced by photothermal
      treatment. In addition, the enhanced uptake can stimulate the production of
      proinflammatory cytokines and remarkably elevate the immune response level.
      Finally, we found that MoS2-PEG-CpG could reduce the proliferative activity of
      cancer cells when co-cultured with a macrophage-like cell upon NIR irradiation,
      implying a novel strategy for multifunctional therapeutics against cancers.

PMID- 28436516
TI  - A non-catalytic vapor growth regime for organohalide perovskite nanowires using
      anodic aluminum oxide templates.
AB  - In this work, a novel and facile synthesis process to fabricate single
      crystalline organometal halide perovskite nanowires has been successfully
      developed. Nanowires were grown in a high density ordered array from metal
      nanoclusters inside anodic aluminum oxide templates using a non-catalytic
      chemical vapor deposition method. Specifically, perovskite NWs were grown as a
      result of the reaction between methylammonium iodide (MAI) and the Pb/Sn (Pb or
      Sn) metal in anodic aluminum oxide templates under optimal conditions. The
      characterization results show that there is a reaction zone at the interface
      between the perovskite material and metal, at the bottom of the anodic aluminum
      oxide nanochannels. In order to sustain perovskite NW growth, MAI molecules have
      to diffuse downward through the perovskite NWs to reach the reaction zone. In
      fact, the reaction is facilitated by the formation of an intermediate product of
      the metal iodide compound. This suggests that the Pb/Sn metal is converted to
      PbI2/SnI2 first and then perovskite NWs are formed as a result of the reaction
      between MAI and PbI2/SnI2 through a vapor-solid-solid process. The optical
      characterization results demonstrate that the as-synthesized NWs with an ultra
      high nanostructure density can serve as ideal candidates for optoelectronic
      devices, such as solar cells, light-emitting didoes, photodetectors, etc. And the
      reported growth approach here is highly versatile combining the merits of
      excellent controllability, cost-effectiveness and tunability on material
      composition and physical properties.

PMID- 28436515
TI  - Exploring the reversal of enantioselectivity on a zinc-dependent alcohol
      dehydrogenase.
AB  - Alcohol Dehydrogenase (ADH) enzymes catalyse the reversible reduction of
      prochiral ketones to the corresponding alcohols. These enzymes present two
      differently shaped active site pockets, which dictate their substrate scope and
      selectivity. In this study, we computationally evaluate the effect of two
      commonly reported active site mutations (I86A, and W110T) on a secondary alcohol
      dehydrogenase from Thermoanaerobacter brockii (TbSADH) through Molecular Dynamics
      simulations. Our results indicate that the introduced mutations induce dramatic
      changes in the shape of the active site, but most importantly they impact the
      substrate-enzyme interactions. We demonstrate that the combination of Molecular
      Dynamics simulations with the tools POVME and NCIplot corresponds to a powerful
      strategy for rationalising and engineering the stereoselectivity of ADH variants.

PMID- 28436518
TI  - Solution behaviour of poly(N-isopropylacrylamide) stereoisomers in water: a
      molecular dynamics simulation study.
AB  - The water affinity of poly(N-isopropylacrylamide), PNIPAM, is tuned by tacticity,
      since the hydrophobicity rises with the increase of the degree of isotacticity.
      On the basis of this experimental evidence, atomistic molecular dynamics
      simulations of pairs of PNIPAM stereoisomers in 1.6% w/w polymer aqueous
      solution, a condition intermediate between the dilute and semidilute regimes,
      were carried out to comparatively investigate the solution behaviour and
      hydration of atactic and isotactic-rich PNIPAMs, both below and above the lower
      critical solution temperature, LCST. 30-mers with contents of meso dyads, m, of
      45% and 59%, built assuming a Bernoullian dyad distribution, are used as models
      since their stereochemical composition corresponds to that of experimentally
      characterized PNIPAM stereoisomers. The simulation results at 283 K, below the
      LCST, show a slight influence of tacticity on the chain size, but a higher
      propensity for inter-chain association of the meso-dyad-rich system, in agreement
      with the experimental results. Junctions between chains are formed because of
      hydrophobic interactions and are stabilized by a layer of hydrogen bonded water
      molecules, whose mobility is reduced as compared to that observed for the same
      meso-dyad-rich stereoisomer at infinite dilution. At 323 K, above the LCST,
      simulations detect both the coil-globule transition and the aggregation of
      chains. Under these conditions, the influence of tacticity on the characteristics
      of PNIPAM aggregate is negligible.

PMID- 28436517
TI  - Real-time measurement of the intracellular pH of yeast cells during glucose
      metabolism using ratiometric fluorescent nanosensors.
AB  - Intracellular pH is a key parameter that influences many biochemical and
      metabolic pathways that can also be used as an indirect marker to monitor
      metabolic and intracellular processes. Herein, we utilise ratiometric fluorescent
      pH-sensitive nanosensors with an extended dynamic pH range to measure the
      intracellular pH of yeast (Saccharomyces cerevisiae) during glucose metabolism in
      real-time. Ratiometric fluorescent pH-sensitive nanosensors consisting of a
      polyacrylamide nanoparticle matrix covalently linked to two pH-sensitive
      fluorophores, Oregon green (OG) and 5(6)carboxyfluorescein (FAM), and a reference
      pH-insensitive fluorophore, 5(6)carboxytetramethylrhodamine (TAMRA), were
      synthesised. Nanosensors were functionalised with acrylamidopropyltrimethyl
      ammonium hydrochloride (ACTA) to confer a positive charge to the nanoparticle
      surfaces that facilitated nanosensor delivery to yeast cells, negating the need
      to use stress inducing techniques. The results showed that under glucose-starved
      conditions the intracellular pH of yeast population (n ~ 200) was 4.67 +/- 0.15.
      Upon addition of d-(+)-glucose (10 mM), this pH value decreased to pH 3.86 +/-
      0.13 over a period of 10 minutes followed by a gradual rise to a maximal pH of
      5.21 +/- 0.26, 25 minutes after glucose addition. 45 minutes after the addition
      of glucose, the intracellular pH of yeast cells returned to that of the glucose
      starved conditions. This study advances our understanding of the interplay
      between glucose metabolism and pH regulation in yeast cells, and indicates that
      the intracellular pH homestasis in yeast is highly regulated and demonstrates the
      utility of nanosensors for real-time intracellular pH measurements.

PMID- 28436520
TI  - Multimetallic complexes: synthesis and applications.

PMID- 28436519
TI  - A ruthenium(ii) bis(phosphinophosphinine) complex as a precatalyst for transfer
      hydrogenation and hydrogen-borrowing reactions.
AB  - The 2-phosphinophosphinine 2-PPh2-3-Me-6-SiMe3-PC5H2 (2) has been prepared and
      was shown to act as a kappa2-chelating ligand in cis-[RuCl2(2)2] (4). Complex 4
      was a competent precatalyst for the room temperature transfer hydrogenation of
      acetophenone (0.1 mol% 4 and 0.5 mol% KOtBu) and the conversion of
      methanol/ethanol mixtures to the advanced biofuel isobutanol in 50% yield and 96%
      selectivity.

PMID- 28436521
TI  - Well incorporation of carbon nanodots with silicon nanowire arrays featuring
      excellent photocatalytic performances.
AB  - Recently, silicon (Si) nanowires have been intensively applied for a wide range
      of optoelectronic applications. Nevertheless, rare explorations considering the
      photodegradation of organic pollutants based on Si nanowires were performed, and
      they still require vast improvement, in particular for their degradation
      efficiency. In this study, broad-band and high efficiency photocatalytic systems
      were demonstrated through the good incorporation of Si nanowires with highly
      fluorescent carbon nanodots. The photodegradation rate of these intriguing
      heterostructure arrays under a 580 nm light illumination is approximately 6 times
      higher than that of sole Si nanowires, and more than 3.6 and 4.5 times higher
      than that of Si nanowire incorporated with silver and gold nanoparticles,
      respectively. Optimizing the luminescent behaviors of carbon nanodots leads to
      the involvement of multiple light sources that activate the photoexcitation of
      carriers within the Si nanowires. This feature was further elucidated by
      examining the corresponding photocurrents under light illumination, which
      presents currents 1.9 times higher than those with the sole Si nanowires. In
      combination with excellent wettability with dye solutions, the present
      heterostructured nanowire arrays have promised the robust photocatalytic
      capability with retained efficiency after cycling uses, which may open up unique
      opportunities for future pollutant detoxification and wastewater treatment.

PMID- 28436522
TI  - Integrated hydrogen evolution and water-cleaning via a robust graphene supported
      noble-metal-free Fe1-xCoxS2 system.
AB  - In an electrocatalytic hydrogen evolution reaction (HER) system, a cathodic H+
      resource, an anodic sacrificial agent and a robust catalyst are three essential
      factors. Industry wastewater emissions, containing high levels of acidity and
      organic dyes, actually can satisfy the material requirements for the HER. Herein,
      a new HER method is proposed, taking acidic ions from wastewater as a cathodic
      resource to produce H2, while organic dye waste acts as an anodic sacrifice to
      balance the reaction. In such a way, a sustainable H2 energy source can be
      generated and clean water is obtained as well. For the HER catalyst, low cost and
      highly efficient graphene supported Fe1-xCoxS2 was synthesized with an onset
      overpotential of ~50 mV and it demonstrated impressive HER performance in both
      practical industry wastewater and analogous wastewater simulations. Besides the
      cathodic H2 evolution, anodic organic dyes (MO, MB, RhB and industry waste
      organic dyes) were all entirely decomposed within 8 min, 18 min, 9 min and 4 h
      under oxidation potentials of ~1.46, 1.50, 1.47 and 1.40 V. As verified both in
      practical industry wastewater and wastewater simulations in the laboratory, our
      approach for integrating the HER and wastewater treatment puts forward an
      attractive opportunity in energy and environmental research fields.

PMID- 28436523
TI  - Mechanistic insights into the selective cyclization of indolines with alkynes and
      alkenes to produce six- and seven-membered 1,7-fused indolines via Rh(iii)
      catalysis: a theoretical study.
AB  - The coupling reaction mechanisms of the Rh(iii)-catalyzed redox-neutral C7
      selective aryl C-H functionalization of indolines with alkynes and alkenes have
      been theoretically investigated with the aid of the density functional theory
      (DFT) calculations. Our calculation results indicate that the active catalyst in
      this system is the cationic species [Cp*Rh(OAc)]+ (2cat) instead of the neutral
      species Cp*Rh(OAc)2 (1cat). The origin of forming different products associated
      with using different coupling partners was also rationalized in detail. For the
      coupling reaction of N-methoxycarbamoyl-protected indoline (1a) with alkyl alkyne
      (4a), the electronic effect plays a dominant role and causes the six-membered
      ring product to be the main product. For the coupling reaction of 1a with aryl
      alkyne (2a), through the replacement of alkyl alkyne with aryl alkyne, the steric
      effect serves as a crucial factor, compared with the electronic effect, and leads
      to the main seven-membered ring product. For the coupling reaction of 1a with
      acrylate (6a), the chemoselectivity is dictated by the steric effect and
      electronic effect.

PMID- 28436524
TI  - TiO2 and Cu1.5Mn1.5O4 co-modified hierarchically porous zeolite Beta for soot
      oxidation with excellent sulfur-resistance and stability.
AB  - TiO2 and spinel Cu1.5Mn1.5O4 co-modified hierarchically porous zeolite Beta
      (Ti/Cu1.5Mn1.5O4-HBeta) with 3D interpenetrating micro-mesoporosity has been
      synthesized, which showed highly efficient catalytic activity to the soot
      oxidation in the presence of O2/NO/N2 due to the rich moderate intensity acidic
      sites and chemisorbed oxygen species. In the presence of SO2/O2/NO/N2, the SO2
      could be preferentially adsorbed on the Ti/Cu1.5Mn1.5O4-HBeta and the resulting
      sulfates could easily decompose at elevated temperatures, thus leading to
      significantly improved sulfur-resistance. Furthermore, the excellent water
      resistance and cycling stability were achieved on the catalyst Ti/Cu1.5Mn1.5O4
      HBeta owing to its crystalline zeolite framework and highly dispersed active
      components.

PMID- 28436525
TI  - Graphitic-C3N4 nanosheets: synergistic effects of hydrogenation and n/n junctions
      for enhanced photocatalytic activities.
AB  - The increasing concern about environmental pollution and fossil fuel energies
      have urged researchers to seek renewable energy sources and methods for pollutant
      decomposition. Photocatalysis seems to be one of the most promising approaches,
      which uses natural sunlight to produce hydrogen from water and removes organic
      pollutants from the environment. Among the various photocatalysts, graphitic
      carbon nitride (g-C3N4) has recently attracted much attention as a metal-free
      photocatalyst; however, it did not give a satisfactory performance. In this
      report, hydrogenation and n/n junctions are combined to improve the
      photocatalytic activities of g-C3N4 nanosheets for both photocatalytic hydrogen
      generation and the degradation of organic pollutants. The hydrogen evolution
      activity is enhanced 3.72 times, and the photocatalytic activity in pollution
      removal is improved 12.38 times from the synergistic effects of hydrogenation and
      n/n junctions in g-C3N4. Thus, this study may trigger more exciting discoveries
      in catalyst designs for various photocatalytic renewable energy applications.

PMID- 28436526
TI  - Structural implications on the excitation dynamics of fluorescent 3H-indolium
      cations.
AB  - Fluorescent 3H-indolium cations are valuable components for the realization of
      activatable fluorophores for bioimaging applications. Their relatively poor
      fluorescent quantum yields in organic solvents, however, appear to be in
      contradiction to their good performance in analytical methods based on single
      molecule detection. The elucidation of the structural factors governing the
      excitation dynamics of these compounds is, therefore, essential to rationalize
      these effects and possibly guide the future design of activatable probes with
      improved performance. In this context, the structural, photochemical and
      photophysical properties of a model compound, consisting of coumarin and 3H
      indolium heterocycles separated by a [C-C[double bond, length as m-dash]C-C]
      bridge, were characterized with a combination of experimental and theoretical
      analyses. These studies demonstrate that the fast rotation about the [C-C] bond
      adjacent to the coumarin component competes with the radiative deactivation of
      the excited state in nonviscous environments. This geometrical change dislodges
      the coumarin and 3H-indolium cations out of planarity to allow the population of
      a weakly-emissive twisted intramolecular charge-transfer (TICT) state and produce
      fluorescence with low quantum yield. In viscous environments, the conformational
      change is slow and cannot compete effectively with the radiative deactivation of
      the excited state, which instead produces fluorescence with high quantum yield.
      These results indicate that structural modifications aimed at the restriction of
      the rotation of this [C-C] bond are essential to improve considerably the
      fluorescence quantum yield of this chromophoric platform. Should a synthetic
      strategy for the implementation of these design guidelines be identified,
      activatable fluorophores, based on the 3H-indolium platform, with improved
      brightness will ultimately emerge.

PMID- 28436527
TI  - Electrowetting on conductors: anatomy of the phenomenon.
AB  - We have recently reported that reversible electrowetting can be observed on the
      basal plane of graphite, without the presence of a dielectric layer, in both
      liquid/air and liquid/liquid configurations. The influence of carbon structure on
      the wetting phenomenon is investigated in more detail here. Specifically, it is
      shown that the adsorption of adventitious impurities on the graphite surface
      markedly suppresses the electrowetting response. Similarly, the use of pyrolysed
      carbon films, although exhibiting a roughness below the threshold previously
      identified as the barrier to wetting on basal plane graphite, does not give a
      noticeable electrowetting response, which leads us to conclude that specific
      interactions at the water-graphite interface as well as graphite crystallinity
      are responsible for the reversible response seen in the latter case. Preliminary
      experiments on mechanically exfoliated and chemical vapour deposition grown
      graphene are also reported.

PMID- 28436528
TI  - A highly selective and sensitive fluorescent probe for Cu2+ based on a novel
      naphthalimide-rhodamine platform and its application in live cell imaging.
AB  - Copper plays important roles in a variety of fundamental physiological processes.
      At the cell organelle level, aberrant copper homeostasis in lysosomes can lead to
      various serious diseases. Herein, a bifluorophore-based, lysosome-targetable Cu2+
      selective ratiometric fluorescent probe (V) has been synthesized by reasonable
      design. The probe V shows high selectivity toward Cu2+ ions over other cations
      and exhibits high sensitivity (1.45 nM) for the detection of Cu2+ ions.
      Meanwhile, the probe is cell permeable and suitable for ratiometric visualization
      of lysosomal Cu2+ in the living cell.

PMID- 28436529
TI  - Modifying surface forces through control of surface potentials.
AB  - Combining direct surface force measurements with in situ regulation of surface
      potential provides an exceptional opportunity for investigating and manipulating
      interfacial phenomena. Recently, we studied the interaction between gold and mica
      surfaces in water with no added salt, while controlling the metal potential, and
      found that the surface charge at the metal may vary, and possibly even change its
      sign, as it progressively approaches the (constant-charge) mica surface
      [Langmuir, 2015, 31(47), 12845-12849]. Such a variation was found to directly
      affect the nature of the contact and adhesion between them due to exclusion of
      all mobile counterions from the intersurface gap. In this work, we extend this to
      examine the potential-dependent response of the adhesion and interaction between
      gold and mica to externally applied voltages and in electrolyte solution. Using a
      surface force balance (SFB) combined with a three-electrode electrochemical cell,
      we measured the normal interaction between gold and mica under surface potential
      regulation, revealing three interaction regimes - pure attraction, non-monotonic
      interaction from electrostatic repulsion to attraction (owing to charge
      inversion) and pure repulsion. Accordingly, the adhesion energy between the
      surfaces was found to vary both in no added salt water and, more strongly, in
      electrolyte solution. We justify this potential-dependent variation of adhesion
      energy in terms of the interplay between electrostatic energy and van der Waals
      (vdW) interaction at contact, and attribute the difference between the two cases
      to the weaker vdW interaction in electrolyte solution. Finally, we showed that
      through abruptly altering the gold surface potential from negative to positive
      and vice versa, the adhesion between gold and mica can be reversibly switched on
      and off. We surmise that the process of bringing the surface into contact is
      associated with the formation of a strong electric field O (108 V m-1) in the
      intersurface gap.

PMID- 28436530
TI  - Solvent-free, uncatalyzed asymmetric "ene" reactions of N-tert-butylsulfinyl
      3,3,3-trifluoroacetaldimines: a general approach to enantiomerically pure alpha
      (trifluoromethyl)tryptamines.
AB  - A novel approach to regioselectively substituted and stereoselectively alpha
      trifluoromethylated tryptamines is reported based on the ene reaction of Boc
      protected 3-methyleneindolines with optically pure (R)- or (S)-tert
      butanesulfinyltrifluoroacetaldimine. Boc- and sulfinylamido-protected alpha
      trifluoromethyltryptamines are obtained in 60-70% yield and 85/15 dr by just
      heating equimolar amounts of the two reaction partners at 80-90  degrees C for 2
      3 h without a solvent. The absolute configuration of the amino alpha-carbon has
      been assigned based on the vibrational circular dichroism (VCD) spectral
      analysis. The two protecting group can be chemoselectively removed allowing
      further regio- and stereoselective elaboration of the ene products to various
      biologically interesting compounds.

PMID- 28436532
TI  - Bis(phenylimidazoselenazolyl) diselenide elicits antinociceptive effect by
      modulating myeloperoxidase activity, NOx and NFkB levels in the collagen-induced
      arthritis mouse model.
AB  - : Bis(phenylimidazoselenazolyl) diselenide (BPIS) is an organoselenium with acute
      antinociceptive and antioxidant properties. OBJECTIVES: The aim of this study was
      to investigate BPIS effect on a collagen-induced arthritis (CIA) model in mice.
      METHODS: Protocol of exposure consisted in arthritis induction by chicken
      collagen type II on day 0 with booster injection on day 21. On day 60 after
      collagen injection, incidence of mechanic allodynia (Von Frey test) or thermal
      hyperalgesia (hot plate test) was evaluated. During following 5 days, mice were
      treated with BPIS (0.1-1 mg/kg; p.o.; daily) or vehicle. On day 65, mice were
      killed, and paws and spinal cord were removed for analyses. KEY FINDINGS: Mice
      submitted to CIA model developed both mechanical allodynia and thermal
      hyperalgesia, which were reversed by BPIS at the highest dose. In paw, BPIS
      reversed the increase in myeloperoxidase activity in the CIA group. In the spinal
      cord, BPIS decreased NOx and NFkB levels increased in the CIA group. BPIS-treated
      animals had lower cyclooxygenase-2 levels in the spinal cord. CONCLUSIONS: The
      myeloperoxidase activity in paw and NOx and NFkB levels in spinal cord are
      related to antinociceptive properties of BPIS in CIA model.

PMID- 28436531
TI  - International inter-rater agreement in scoring acne severity utilizing cloud
      based image sharing of mobile phone photographs.
AB  - BACKGROUND: Cloud-based image sharing technology allows facilitated sharing of
      images. Cloud-based image sharing technology has not been well-studied for acne
      assessments or treatment preferences, among international evaluators. We
      evaluated inter-rater variability of acne grading and treatment recommendations
      among an international group of dermatologists that assessed photographs.
      METHODS: This is a prospective, single visit photographic study to assess inter
      rater agreement of acne photographs shared through an integrated mobile device,
      cloud-based, and HIPAA-compliant platform. Inter-rater agreements for global acne
      assessment and acne lesion counts were evaluated by the Kendall's coefficient of
      concordance while correlations between treatment recommendations and acne
      severity were calculated by Spearman's rank correlation coefficient. RESULTS:
      There was good agreement for the evaluation of inflammatory lesions (KCC = 0.62,
      P < 0.0001), noninflammatory lesions (KCC = 0.62, P < 0.0001), and the global
      acne grading system score (KCC = 0.69, P < 0.0001). Topical retinoid, oral
      antibiotic, and isotretinoin treatment preferences correlated with photographic
      based acne severity. CONCLUSIONS: Our study supports the use of mobile phone
      based photography and cloud-based image sharing for acne assessment. Cloud-based
      sharing may facilitate acne care and research among international collaborators.

PMID- 28436533
TI  - Left atrial appendage electrical isolation for atrial fibrillation: "ICE and
      FIRE".

PMID- 28436534
TI  - A novel TRPA1 variant is associated with carbamazepine-responsive cramp
      fasciculation syndrome.
AB  - Cramp-fasciculation syndrome (CFS) is a rare muscle hyperexcitability syndrome
      that presents with muscle cramps, fasciculations, and stiffness, as well as pain,
      fatigue, anxiety, hyperreflexia, and paresthesias. Although familial cases have
      been reported, a genetic etiology has not yet been identified. We performed whole
      exome sequencing followed by validation and cosegregation analyses on a father
      son pair with CFS. Both subjects manifested other hypersensitivity
      hyperexcitability symptoms, including asthma, gastroesophageal reflux, migraine,
      restless legs syndrome, tremor, cold hyperalgesia, and cardiac conduction
      defects. Most symptoms improved with carbamazepine, consistent with an underlying
      cation channelopathy. We identified a variant in the transient receptor potential
      ankyrin A1 channel (TRPA1) gene that selectively cosegregated with CFS and the
      other hypersensitivity-hyperexcitability symptoms. This variant (c.2755C>T)
      resulted in a premature stop codon at amino acid 919 (p.Arg919*) in the outer
      pore of the channel. TRPA1 is a widely distributed, promiscuous plasmalemmal
      cation channel that is strongly implicated in the pathophysiology of the specific
      hypersensitivity-hyperexcitability symptoms observed in these subjects. Thus, we
      have identified a novel TRPA1 variant that is associated with CFS as part of a
      generalized hypersensitivity-hyperexcitability disorder. These findings clarify
      the diverse functional roles of TRPA1, and underscore the importance of this
      channel as a potential therapeutic target.

PMID- 28436535
TI  - The role of the long-range exchange corrections in the description of electron
      delocalization in aromatic species.
AB  - In this article, we address the role of the long-range exchange corrections in
      description of the cyclic delocalization of electrons in aromatic systems at the
      density functional theory level. A test set of diversified monocyclic and
      polycyclic aromatics is used in benchmark calculations involving various exchange
      correlation functionals. A special emphasis is given to the problem of local
      aromaticity in acenes, which has been a subject of long-standing debate in the
      literature. The presented results indicate that the noncorrected exchange
      correlation functionals significantly overestimate cyclic delocalization of
      electrons in heteroaromatics and aromatic systems with fused rings, which in the
      case of acenes leads to conflicting local aromaticity predictions from different
      criteria. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436536
TI  - Early vertebrate origin and diversification of small transmembrane regulators of
      cellular ion transport.
AB  - KEY POINTS: Small transmembrane proteins such as FXYDs, which interact with Na+
      ,K+ -ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum
      Ca2+ -ATPase play fundamental roles in regulation of ion transport in
      vertebrates. Uncertain evolutionary origins and phylogenetic relationships among
      these regulators of ion transport have led to inconsistencies in their
      classification across vertebrate species, thus hampering comparative studies of
      their functions. We discovered the first FXYD homologue in sea lamprey, a basal
      jawless vertebrate, which suggests small transmembrane regulators of ion
      transport emerged early in the vertebrate lineage. We also identified 13 gene
      subfamilies of FXYDs and propose a revised, phylogeny-based FXYD classification
      that is consistent across vertebrate species. These findings provide an improved
      framework for investigating physiological and pathophysiological functions of
      small transmembrane regulators of ion transport. ABSTRACT: Small transmembrane
      proteins are important for regulation of cellular ion transport. The most
      prominent among these are members of the FXYD family (FXYD1-12), which regulate
      Na+ ,K+ -ATPase, and phospholamban, sarcolipin, myoregulin and DWORF, which
      regulate the sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA). FXYDs and
      regulators of SERCA are present in fishes, as well as terrestrial vertebrates;
      however, their evolutionary origins and phylogenetic relationships are obscure,
      thus hampering comparative physiological studies. Here we discovered that sea
      lamprey (Petromyzon marinus), a representative of extant jawless vertebrates
      (Cyclostomata), expresses an FXYD homologue, which strongly suggests that FXYDs
      predate the emergence of fishes and other jawed vertebrates (Gnathostomata).
      Using a combination of sequence-based phylogenetic analysis and conservation of
      local chromosome context, we determined that FXYDs markedly diversified in the
      lineages leading to cartilaginous fishes (Chondrichthyes) and bony vertebrates
      (Euteleostomi). Diversification of SERCA regulators was much less extensive,
      indicating they operate under different evolutionary constraints. Finally, we
      found that FXYDs in extant vertebrates can be classified into 13 gene
      subfamilies, which do not always correspond to the established FXYD
      classification. We therefore propose a revised classification that is based on
      evolutionary history of FXYDs and that is consistent across vertebrate species.
      Collectively, our findings provide an improved framework for investigating the
      function of ion transport in health and disease.

PMID- 28436537
TI  - Error-prone replication bypass of the imidazole ring-opened formamidopyrimidine
      deoxyguanosine adduct.
AB  - Addition of hydroxyl radicals to the C8 position of 2'-deoxyguanosine generates
      an 8-hydroxyguanyl radical that can be converted into either 8-oxo-7,8-dihydro-2'
      deoxyguanosine or N-(2-deoxy-d-pentofuranosyl)-N-(2,6-diamino-4-hydroxy-5
      formamidopyrimidine) (Fapy-dG). The Fapy-dG adduct can adopt different
      conformations and in particular, can exist in an unnatural alpha anomeric
      configuration in addition to canonical beta configuration. Previous studies
      reported that in 5'-TGN-3' sequences, Fapy-dG predominantly induced G -> T
      transversions in both mammalian cells and Escherichia coli, suggesting that
      mutations could be formed either via insertion of a dA opposite the 5' dT due to
      primer/template misalignment or as result of direct miscoding. To address this
      question, single-stranded vectors containing a site-specific Fapy-dG adduct were
      generated to vary the identity of the 5' nucleotide. Following vector replication
      in primate cells (COS7), complex mutation spectra were observed that included ~3
      5% G -> T transversions and ~14-21% G -> A transitions. There was no correlation
      apparent between the identity of the 5' nucleotide and spectra of mutations. When
      conditions for vector preparation were modified to favor the beta anomer,
      frequencies of both G -> T and G -> A substitutions were significantly reduced.
      Mutation frequencies in wild-type E. coli and a mutant deficient in damage
      inducible DNA polymerases were significantly lower than detected in COS7 and
      spectra were dominated by deletions. Thus, mutagenic bypass of Fapy-dG can
      proceed via mechanisms that are different from the previously proposed
      primer/template misalignment or direct misinsertions of dA or dT opposite to the
      beta anomer of Fapy-dG. Environ. Mol. Mutagen. 58:182-189, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28436539
TI  - Valuing Equal Protection in Aviation Security Screening.
AB  - The growing number of anti-terrorism policies has elevated public concerns about
      discrimination. Within the context of airport security screening, the current
      study examines how American travelers value the principle of equal protection by
      quantifying the "equity premium" that they are willing to sacrifice to avoid
      screening procedures that result in differential treatments. In addition, we
      applied the notion of procedural justice to explore the effect of alternative
      selective screening procedures on the value of equal protection. Two-hundred and
      twenty-two respondents were randomly assigned to one of three selective screening
      procedures: (1) randomly, (2) using behavioral indicators, or (3) based on
      demographic characteristics. They were asked to choose between airlines using
      either an equal or a discriminatory screening procedure. While the former
      requires all passengers to be screened in the same manner, the latter mandates
      all passengers undergo a quick primary screening and, in addition, some
      passengers are selected for a secondary screening based on a predetermined
      selection criterion. Equity premiums were quantified in terms of monetary cost,
      wait time, convenience, and safety compromise. Results show that equity premiums
      varied greatly across respondents, with many indicating little willingness to
      sacrifice to avoid inequitable screening, and a smaller minority willing to
      sacrifice anything to avoid the discriminatory screening. The selective screening
      manipulation was effective in that equity premiums were greater under selection
      by demographic characteristics compared to the other two procedures.

PMID- 28436538
TI  - Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new
      combined score for clinical trials.
AB  - BACKGROUND: Two recent, randomized, placebo-controlled phase II/III trials
      (clinicaltrials.gov: NCT01110720, NCT01049399) of davunetide and tideglusib in
      progressive supranuclear palsy (PSP) generated prospective, 1-year longitudinal
      datasets of high-resolution T1-weighted three-dimensional MRI. OBJECTIVE: The
      objective of this study was to develop a quantitative MRI disease progression
      measurement for clinical trials. METHODS: The authors performed a fully automated
      quantitative MRI analysis employing atlas-based volumetry and provide sample size
      calculations based on data collected in 99 PSP patients assigned to placebo in
      these trials. Based on individual volumes of 44 brain compartments and structures
      at baseline and 52 weeks of follow-up, means and standard deviations of
      annualized percentage volume changes were used to estimate standardized effect
      sizes and the required sample sizes per group for future 2-armed, placebo
      controlled therapeutic trials. RESULTS: The highest standardized effect sizes
      were found for midbrain, frontal lobes, and the third ventricle. Using the
      annualized percentage volume change of these structures to detect a 50% change in
      the 1-year progression (80% power, significance level 5%) required lower numbers
      of patients per group (third ventricle, n = 32; midbrain, n = 37; frontal lobe, n
      = 43) than the best clinical scale (PSP rating scale total score, n = 58). A
      combination of volume changes in these 3 structures reduced the number of
      required patients to only 20 and correlated best with the progression in the
      clinical scales. CONCLUSIONS: We propose the 1-year change in the volumes of
      third ventricle, midbrain, and frontal lobe as combined imaging read-out for
      clinical trials in PSP that require the least number of patients for detecting
      efficacy to reduce brain atrophy. (c) 2017 International Parkinson and Movement
      Disorder Society.

PMID- 28436540
TI  - Early Diagnosis of Bladder Exstrophy: Quantitative Assessment of a Low-Inserted
      Umbilical Cord.
AB  - OBJECTIVES: Bladder exstrophy is a rare severe congenital malformation. Early
      prenatal diagnosis is scarcely described in the literature. Low insertion of the
      umbilical cord is a constant anatomic feature of bladder exstrophy. The aim of
      our study was to assess whether early measurements of the umbilical cord
      insertion-to-genital tubercle length may serve as quantitative measurements for a
      low-inserted umbilical cord in cases of bladder exstrophy. METHODS: The umbilical
      cord insertion-to-genital tubercle length was prospectively measured in all cases
      referred for a nonvisualized urinary bladder before 18 weeks' gestation. Final
      diagnoses were compared with prenatal measurements. RESULTS: Fifteen fetuses were
      evaluated for a nonvisualized bladder at a mean gestational age of 15.7 weeks
      (range, 14-17 weeks). Of them, 6 cases were diagnosed with bladder exstrophy, and
      9 cases had a normal urinary bladder. All cases with bladder exstrophy had an
      umbilical cord insertion-to-genital tubercle length below the fifth percentile
      for gestational age, whereas cases with a normal bladder had a normal
      measurement. CONCLUSIONS: Fetuses with bladder exstrophy have an umbilical cord
      insertion-to-genital tubercle length below the fifth percentile of the general
      population. This measurement may serve as a complementary objective sonographic
      parameter in the prenatal assessment and counseling of cases suspected of having
      bladder exstrophy during early pregnancy.

PMID- 28436541
TI  - PDX1 -MODY and dorsal pancreatic agenesis: New phenotype of a rare disease.
AB  - Maturity-Onset Diabetes of the Young (MODY) type 4 or PDX1 -MODY is a rare form
      of monogenic diabetes caused by heterozygous variants in PDX1 . Pancreatic
      developmental anomalies related to PDX1 are reported only in neonatal diabetes
      cases. Here, we describe dorsal pancreatic agenesis in 2 patients with PDX1 
      MODY. The proband presented with diabetes since 14 years of age and maintained
      regular glycemic control with low doses of basal insulin and detectable C-peptide
      levels after 38 years with diabetes. A diagnosis of MODY was suspected. Targeted
      next-generation sequencing identified a heterozygous variant in PDX1 :
      c.188delC/p.Pro63Argfs*60. Computed tomography revealed caudal pancreatic
      agenesis. Low fecal elastase indicated exocrine insufficiency. His son had
      impaired glucose tolerance, presented similar pancreatic agenesis, and harbored
      the same allelic variant. The unusual presentation in this Brazilian family
      enabled expansion upon a rare disease phenotype, demonstrating the possibility of
      detecting pancreatic malformation even in cases of PDX1 -related diabetes
      diagnosed after the first year of life. This finding can improve the management
      of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis
      and exocrine dysfunction.

PMID- 28436542
TI  - Intercontinental telehealth coaching of therapists to improve verbalizations by
      children with autism.
AB  - This study examined the effects of intercontinental telehealth coaching on the
      mastery of therapists' skills and improvements in verbalizations by children with
      autism, testing whether telehealth can be a solution for underserved communities
      in developing countries such as Georgia-Sakartvelo in Eastern Europe. Three
      therapists delivering and three children with autism receiving early-intervention
      services from the nongovernmental organization Children of Georgia in Tbilisi
      participated. Experimenters provided coaching from Virginia, USA to therapists in
      Georgia-Sakartvelo. Observers in Georgia-Sakartvelo and in Virginia conducted the
      behavioral observations. We used inexpensive communications technology to provide
      the coaching and a multiple-baseline design across participants to evaluate the
      effects of the intervention. Therapists demonstrated improvements in two classes
      of behaviors: correct command sequences and positive consequences. The children
      demonstrated improvements with echoics and mands. The study demonstrated that
      telehealth can be a good model for delivering early-intervention services to
      children with autism in underserved and distant regions of the world.

PMID- 28436543
TI  - Facile Formation of a Solid Electrolyte Interface as a Smart Blocking Layer for
      High-Stability Sulfur Cathode.
AB  - The practical application of lithium-sulfur batteries (LSBs) is hindered by their
      poor cycle life, which stems mainly from the "redox shuttle reactions" of
      dissolved polysulfides. To develop a high-performance cathode for LSBs,
      encapsulation of polysulfides with a blocking layer is potentially
      straightforward. Herein, a novel strategy is reported encapsulate sulfur and the
      electrolyte together in porous carbon spheres by using a solid electrolyte
      interface (SEI) that can selectively sieve Li+ ions while efficiently avoiding
      polysulfide accumulation and suppressing undesired polysulfide migration. This
      strategy is simple, straightforward, and effective. The carbon/sulfur cathode
      only needs to be cycled a few times within a voltage window of 0.3-1.0 V to form
      such a smart SEI, allowing the resulting cathode to exhibit superior stability
      extending 600 cycles. This strategy can be combined with other existing advanced
      sulfur cathode designs to improve the overall performance of LSBs.

PMID- 28436544
TI  - Screening tools for tic disorders-Focus on development or implementation?

PMID- 28436545
TI  - Training Basic Visual Attention Leads to Changes in Responsiveness to Social
      Communicative Cues in 9-Month-Olds.
AB  - This study investigated transfer effects of gaze-interactive attention training
      to more complex social and cognitive skills in infancy. Seventy 9-month-olds were
      assigned to a training group (n = 35) or an active control group (n = 35).
      Before, after, and at 6-week follow-up both groups completed an assessment
      battery assessing transfer to nontrained aspects of attention control, including
      table top tasks assessing social attention in seminaturalistic contexts. Transfer
      effects were found on nontrained screen-based tasks but importantly also on a
      structured observation task assessing the infants' likelihood to respond to an
      adult's social-communication cues. The results causally link basic attention
      skills and more complex social-communicative skills and provide a principle for
      studying causal mechanisms of early development.

PMID- 28436546
TI  - Corrigendum: The impact of early environmental interventions on structural
      plasticity of the axon initial segment in neocortex. M. Nozari, T. Suzuki, M. G.
      P. Rosa, K. Yamakawa, and N. Atapour.

PMID- 28436547
TI  - Are Type D personality and depression predictors of anxiety and posttraumatic
      stress symptoms among ICD patients?

PMID- 28436548
TI  - An open-source framework for analyzing N-electron dynamics. I. Multideterminantal
      wave functions.
AB  - The aim of the present contribution is to provide a framework for analyzing and
      visualizing the correlated many-electron dynamics of molecular systems, where an
      explicitly time-dependent electronic wave packet is represented as a linear
      combination of N-electron wave functions. The central quantity of interest is the
      electronic flux density, which contains all information about the transient
      electronic density, the associated phase, and their temporal evolution. It is
      computed from the associated one-electron operator by reducing the
      multideterminantal, many-electron wave packet using the Slater-Condon rules.
      Here, we introduce a general tool for post-processing multideterminant
      configuration-interaction wave functions obtained at various levels of theory. It
      is tailored to extract directly the data from the output of standard quantum
      chemistry packages using atom-centered Gaussian-type basis functions. The
      procedure is implemented in the open-source Python program detCI@ORBKIT, which
      shares and builds on the modular design of our recently published post-processing
      toolbox (Hermann et al., J. Comput. Chem. 2016, 37, 1511). The new procedure is
      applied to ultrafast charge migration processes in different molecular systems,
      demonstrating its broad applicability. Convergence of the N-electron dynamics
      with respect to the electronic structure theory level and basis set size is
      investigated. This provides an assessment of the robustness of qualitative and
      quantitative statements that can be made concerning dynamical features observed
      in charge migration simulations. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436549
TI  - Atrial undersensing secondary to quiet timer blanking in pediatric and congenital
      heart disease patients.
AB  - BACKGROUND: Atrial undersensing despite normal atrial lead parameters and high
      amplitude electrograms has been described in adult patients as a consequence of
      atrial amplifier saturation. Repetitive inputs cause amplifier ringing and
      undersensing occurs as a consequence of quiet timer blanking. High amplitude
      ventricular electrograms can also result in atrial blanking secondary to cross
      chamber effect. This has not been described in pediatric patients or epicardial
      pacing systems and specific risk factors are not known. We describe five cases of
      atrial undersensing in pediatric and congenital heart disease patients with
      epicardial dual-chamber systems and high ventricular lead outputs. METHODS: This
      was a retrospective cohort study of all patients with dual-chamber pacing systems
      cared for at the Heart Institute at Children's Hospital Colorado. RESULTS: Five
      cases of atrial undersensing with normal atrial lead parameters were found. All
      were epicardial systems with acceptable lead parameters at implantation and
      Medtronic (Medtronic, Inc., Minneapolis, MN, USA) generators with unipolar leads.
      Ventricular pacing outputs were elevated at presentation, median 5.5 V (5-7.5).
      Presenting symptoms were exercise intolerance (four) and detection on routine
      monitoring (one). Successful interventions included reduction in ventricular lead
      pacing output (one), programming of rate response (two), and implantation of an
      alternative generator manufacturer (two). CONCLUSION: Atrial undersensing
      secondary to amplifier ringing and quiet timer blanking is an uncommon
      presentation but may be clinically important in patients with unipolar epicardial
      atrial leads and high pacing outputs from ventricular leads.

PMID- 28436550
TI  - Epicardial Brugada syndrome ablation unmasking inferior J waves.
AB  - Patients with Brugada syndrome are at risk of life-threatening ventricular
      arrhythmias. Epicardial substrate ablation for Brugada syndrome has been
      described as a means of controlling these arrhythmias and recent reports describe
      elimination of the Brugada phenotype with ablation. We describe a unique case in
      which a patient developed inferior J waves with an early repolarization-type
      electrocardiogram following successful epicardial infundibular substrate ablation
      (which eliminated the Brugada syndrome electrocardiogram on ajmaline challenge).
      We discuss the likely underlying pathophysiology responsible for this phenomenon,
      its relationship to the anatomic obstacles encountered during epicardial
      ablation, and the implications for long-term arrhythmic risk.

PMID- 28436551
TI  - Genomics and metabolomics of post-weaning return to estrus.
AB  - The weaning-to-estrus interval is a multifaceted trait that has the potential to
      substantially improve production efficiency in today's global swine industry, if
      variation in this measure can be reduced. Systems-biology approaches should help
      close the knowledge gap and increase selection tools and management strategies
      such as gilt development programs, farrowing, and lactation feeding programs-to
      decrease the weaning-to-estrus interval. Metabolomics, the study of small
      compounds within biofluids and tissues, provides links between genotype and
      phenotype. Given the complexity and influence of the environment on the weaning
      to-estrus interval, incorporating metabolomics data will provide valuable insight
      and guidance for future physiological as well as genetic and genomic strategies
      to reduce this interval, thereby improving sow productivity.

PMID- 28436552
TI  - Systematic review with meta-analysis: the efficacy and safety of tenofovir to
      prevent mother-to-child transmission of hepatitis B virus.
AB  - BACKGROUND: Preventing mother to child transmission of chronic hepatitis B
      infection in the setting of a high maternal viral load is challenging. The idea
      has emerged from antepartum tenofovir treatment with combination
      immunoprophylaxis. AIMS: To demonstrate the efficacy and safety of tenofovir to
      prevent mother to child transmission of hepatitis B virus. METHODS: PubMed,
      EMBASE, and Cochrane databases were searched through August 16, 2016. Comparative
      trials of second or third trimester tenofovir administration vs. controls for
      patients with chronic hepatitis B infection and non-comparative case series
      assessing mother to child transmission rates and evaluating maternal and foetal
      safety outcomes were included. RESULTS: Ten studies (one randomised controlled
      trial, four non-randomised controlled trials and five case series) that enrolled
      733 women were included. The pooled results from comparative trials (599
      pregnancies) showed that tenofovir significantly reduced the risk of infant
      hepatitis B surface antigen seropositivity by 77% (odds ratio=0.23, 95%
      confidence intervals=0.10-0.52, P=.0004) without heterogeneity (I2 =0%). In the
      case series analysis (134 pregnancies), only two cases (1.5%) of mother to child
      transmission with extremely high maternal viral load and non-compliance to
      treatment were identified. Maternal and foetal safety parameters including
      congenital malformation and foetal death were re-assuring. CONCLUSIONS: For
      pregnant women with high hepatitis B virus DNA levels, tenofovir administration
      in the second or third trimester can prevent mother to child transmission when
      combined with hepatitis B immunoglobulin and the hepatitis B vaccine. Tenofovir
      is safe and tolerable for both the mother and foetus.

PMID- 28436553
TI  - Stevens-Johnson syndrome probably induced by ambroxol.

PMID- 28436554
TI  - Reply to "Screening tools for tic disorders - Focus on development or
      implementation?"

PMID- 28436555
TI  - Hemodynamics as Measured With Color Doppler Sonography in Early-Stage Obesity
      Related Nephropathy in Children.
AB  - OBJECTIVES: We retrospectively studied hemodynamic changes in the interlobar
      artery to assess the clinical value of color Doppler sonography for detecting
      preclinical obesity-related nephropathy. METHODS: Color Doppler renal sonography
      was performed in 52 children with obesity-related nephropathy and 51 control
      children with simple obesity. The interlobar artery resistive index (RI) was
      measured and compared with clinical data and laboratory indicators. RESULTS: The
      left RI (mean +/- SD, 0.65 +/- 0.05 versus 0.60 +/- 0.08; t = 3.85), right RI
      (0.64 +/- 0.03 versus 0.59 +/- 0.02; t = 10.00), and mean RI (0.64 +/- 0.05
      versus 0.59 +/- 0.06; t = 5.00) revealed large statistically significant
      increases in the obesity-related nephropathy group (all P < .01). In the obesity
      related nephropathy group, a positive correlation was found between the mean RI
      and 24-hour urine trace albumin (r = 0.47; P < .01), triglycerides (r = 0.98; P <
      .01), and body mass index (r = 0.28; P < .05). The 24-hour urine trace albumin
      and triglycerides were higher in the obesity-related nephropathy group than the
      control group (P < .05). In the control group, a mild positive correlation was
      also found between the mean RI and body mass index (r = 0.24; P < .05).
      CONCLUSIONS: Color Doppler sonography successfully indicated renal hemodynamic
      changes and has diagnostic value for early-stage obesity-related nephropathy.

PMID- 28436556
TI  - Theoretical evidence for bond stretch isomerism in Grubbs olefin metathesis.
AB  - A comprehensive density functional theory study on the dissociative and
      associative mechanisms of Grubbs first and second generation olefin metathesis
      catalysis reveals that ruthenacyclobutane intermediate (RuCB) observed in the
      Chauvin mechanism is not unique as it can change to a non-metathetic
      ruthenacyclobutane (RuCB') via the phenomenon of bond stretch isomerism (BSI).
      RuCB and RuCB' differ mainly in RuCalpha , RuCbeta , and Calpha Cbeta bond
      lengths of the metallacycle. RuCB is metathesis active due to the agostic type
      bonding-assisted simultaneous activation of both Calpha Cbeta bonds, giving
      hypercoordinate character to Cbeta whereas an absence of such bonding
      interactions in RuCB' leads to typical CC single bond distances and metathesis
      inactivity. RuCB and RuCB' are connected by a transition state showing moderate
      activation barrier. The new mechanistic insights invoking BSI explains the non
      preference of associative mechanism and the requirement of bulky ligands in the
      Grubbs catalyst design. The present study lifts the status of BSI from a concept
      of largely theoretical interest to a phenomenon of intense importance to describe
      an eminent catalytic reaction. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436557
TI  - Stop, look, and listen: Sleep in movement disorders.

PMID- 28436558
TI  - Adverse effects of pegaspargase in pediatric patients receiving doses greater
      than 3,750 IU.
AB  - BACKGROUND: Increased toxicities have been identified with higher doses of
      pegaspargase (PEG-ASP) in adults. This has led to routine use of a dose cap of
      3,750 IU for adult acute lymphoblastic leukemia (ALL) patients in most
      institutions. In pediatric ALL patients, PEG-ASP is not capped. There is concern
      at our institution that larger doses may result in increased rates of adverse
      effects and that increased monitoring may be warranted in pediatric patients
      receiving doses greater than 3,750 IU. The objective of this study is to quantify
      the difference in the rates of PEG-ASP-associated adverse events between
      pediatric patients who received doses greater than 3,750 IU and less than or
      equal to 3,750 IU. METHODS: Retrospective chart review of patients 1-21 years old
      with pre-B-cell ALL who received PEG-ASP between 2007 and 2014 at an academic
      medical center. RESULTS: Of 183 patients included in the analysis, 24 received
      PEG-ASP doses higher than 3,750 IU and 159 received doses less than or equal to
      3,750 IU. The incidence of venous thromboembolism (VTE) was significantly higher
      for patients in the group that received more than 3,750 IU compared with those
      who received 3,750 IU or less (20.8 vs. 1.89%, respectively; P = 0.0011). The
      incidence of pancreatitis (P = 0.0306) and hyperglycemia (P = 0.0089) were also
      higher in the group that received more than 3,750 IU. CONCLUSIONS: PEG-ASP doses
      higher than 3,750 IU are associated with higher rates of VTE, pancreatitis, and
      hyperglycemia in pediatric patients with pre-B-cell ALL. Patients receiving more
      than 3,750 IU should have increased monitoring, and larger, multicenter trials
      are needed to determine if monitoring, VTE prophylaxis, and potential dose
      capping recommendations should be added to clinical trial protocols.

PMID- 28436559
TI  - Dopamine D1 or D2 receptor-expressing neurons in the central nervous system.
AB  - Dopamine signals mainly through D1 receptors (D1Rs) and D2 receptors (D2Rs); D1R
      expressing or D2R-expressing neurons contribute to distinct reward and addictive
      behaviors. Traditionally, transgenic mice expressing green fluorescent protein
      (GFP) under D1R or D2R promoters are used for fluorescent verification in
      electrophysiology studies, whereas Cre mice are employed for behavioral research.
      However, it is unknown whether the same neuronal populations are targeted in GFP
      and Cre mice. Additionally, while D1Rs and D2Rs are known to be expressed in
      different striatal neurons, their expression patterns outside the striatum remain
      unclear. The present study addressed these two questions by using several
      transgenic mouse lines expressing fluorescent proteins (GFP or tdTomato) or Cre
      under the control of D1R or D2R promoters. We found a high degree of overlap
      between GFP-positive and Cre-positive neurons in the striatum and hippocampus.
      Additionally, we discovered that D1Rs and D2Rs were highly segregated in the
      orbitofrontal cortex, prefrontal cortex, dorsal and ventral hippocampus, and
      amygdala: ~4-34 percent of neurons co-expressed these receptors. Importantly,
      slice electrophysiological studies demonstrated that D1R-positive and D1R
      negative hippocampal neurons were functionally distinct in a mouse line generated
      by crossing Drd1a-Cre mice with a Cre reporter Ai14 line. Lastly, we discovered
      that chronic alcohol intake differentially altered D1R-positive and D2R-positive
      neuron excitability in the ventral CA1. These data suggest that GFP and Cre mice
      target the same populations of striatal neurons, D1R-expressing or D2R-expressing
      neurons are highly segregated outside the striatum, and these neurons in the
      ventral hippocampal may exert distinct roles in alcohol addiction.

PMID- 28436560
TI  - Development of a high-throughput genotoxicity assay using Umu test strains
      expressing human cytochrome P450s and NADPH-P450 reductase and bacterial O
      acetyltransferase.
AB  - Umu test is one of the in vitro genotoxicity test that has been used widely. It
      was developed as a high-throughput test system using the 96-well microplate. We
      have previously constructed new umu test strains for the evaluation of
      genotoxicity of procarcinogenic metabolic products formed by cytochrome P450
      (CYP) enzymes. In this study, a highly sensitive high-throughput genotoxicity
      test was developed using four umu test strains (OY1002/1A1, OY1002/1B1,
      OY1002/1A2, and OY1002/3A4) that express human CYPs and NADPH-P450 reductase. We
      found that the modified umu-microplate method was more sensitive than the
      conventional microplate method using strain OY1002/1A2. In addition, the new
      microplate method was better able to detect genotoxicity than the test tube
      method when the strain OY1002/1A2 was used and had similar sensitivity for the
      remaining three strains. When the microplate method was used, OY1002/1A2 showed
      stronger umuC gene expression in the presence of 2-amino-6-methyldipyrido[1,2
      a:3',2'-d]imidazole, 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,4
      dimethylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2
      aminofluorene, and 2-aminoanthracene compared to other strains. We also confirmed
      CYP1A2 expression in OY1002/1A2 in this condition. These results indicate that
      the microplate version of this test system can detect the genotoxicity of
      heterocyclic and aromatic amines with high sensitivity and can be used for high
      throughput screening of potentially genotoxic compounds. Environ. Mol. Mutagen.
      58:209-216, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28436561
TI  - The interplay between aridity and competition determines colonization ability,
      exclusion and ecological segregation in the heteroploid Brachypodium distachyon
      species complex.
AB  - A higher competitive advantage of polyploid plants compared with their parental
      diploids is frequently invoked to explain their establishment success,
      colonization of novel environments and cytotypic ecological segregation, yet
      there is scarce experimental evidence supporting such hypotheses. Here, we
      investigated whether differential competitive ability of species of the
      Brachypodium distachyon (Poaceae) species complex, a model system for genomic,
      ecological and evolutionary studies of temperate grasses, contributes to
      explaining their ecological segregation as well as their coexistence in
      diploid/allotetraploid contact zones. We conducted two field experiments in dry
      and humid localities to evaluate the tolerance to competition of diploids and
      allotetraploids in densely occupied environments, and to parameterize models of
      intra- and intercytotype competition as a mechanism for species
      exclusion/coexistence. We provide experimental evidence supporting the hypothesis
      that, under natural field conditions, allotetraploids have superior ecological
      success compared with one of their parental diploids in terms of both colonizing
      competitive habitats and intercytotypic competition, with the balance of
      intra/intercytotype competition favoring polyploid population establishment.
      These findings, together with previous data on ecogeographic segregation and
      adaptive response to water stress, suggest that the interplay between aridity and
      competitive outcome determines the ability to colonize competitive environments,
      the exclusion of diploids, especially in arid localities, and species geographic
      segregation.

PMID- 28436562
TI  - Anatomical subgroup analysis of the MERIDIAN cohort: failed commissuration.
AB  - OBJECTIVE: To assess the contribution of fetal magnetic resonance imaging (MRI)
      in fetuses of the MERIDIAN cohort diagnosed with either agenesis or hypogenesis
      of the corpus callosum (referred to collectively as failed commissuration) on
      antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study
      of fetuses with failed commissuration (with or without ventriculomegaly)
      diagnosed on ultrasound in women who had MRI assessment within 2 weeks of
      ultrasound and for whom outcome reference data were available. The diagnostic
      accuracy of ultrasound and MRI was studied, as well as indicators of diagnostic
      confidence and effects on prognosis/clinical management. Appropriate diagnostic
      confidence was assessed by the score-based weighted average method, which
      combines diagnostic accuracy with diagnostic confidence data. RESULTS: In the
      MERIDIAN cohort, 79 fetuses were diagnosed with failed commissuration on
      ultrasound (55 with agenesis and 24 with hypogenesis of the corpus callosum). The
      diagnostic accuracy for detecting failed commissuration was 34.2% for ultrasound
      and 94.9% for MRI (difference, 60.7% (95% CI, 47.6-73.9%), P < 0.0001). The
      diagnostic accuracy for detecting hypogenesis of the corpus callosum as a
      discrete entity was 8.3% for ultrasound and 87.5% for MRI, and for detecting
      agenesis of the corpus callosum as a distinct entity was 40.0% for ultrasound and
      92.7% for MRI. There was a statistically significant improvement in 'appropriate'
      diagnostic confidence when using MRI as assessed by the score-based weighted
      average method (P < 0.0001). Prognostic information given to the women changed in
      36/79 (45.6%) cases after MRI and its overall effect on clinical management was
      'significant', 'major' or 'decisive' in 35/79 cases (44.3%). CONCLUSIONS: Our
      data suggest that any woman whose fetus has failed commissuration as the only
      intracranial finding detected on ultrasound should have MRI examination for
      further evaluation. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28436565
TI  - Self-retaining weighted thermoplastic ampoule holder for aflibercept and
      ranibizumab vials.

PMID- 28436564
TI  - High prevalence of superficial white onychomycosis by Trichophyton interdigitale
      in a Japanese nursing home with a geriatric hospital.
AB  - A mycological survey on feet was performed in a nursing home with a geriatric
      hospital to ascertain the prevalence of tinea lesions. Of 100 subjects,
      comprising 62 in the nursing home and 38 in the geriatric wing, 70 were diagnosed
      with tinea pedis, tinea unguium (onychomycosis) or both of which 54 had
      onychomycosis alone, nine tinea pedis alone and seven had co-existing
      onychomycosis and tinea pedis. The most common clinical type of onychomycosis was
      distal lateral subungual onychomycosis (DLSO) at 30 cases, followed by
      superficial white onychomycosis (SWO) at 23 cases. Fifteen strains of
      Trichophyton (T.) interdigitale isolated from 23 SWO patients comprised six
      molecular types (D2II, nine cases; C2II, two cases; four other types, one case of
      each), based on the non-transcribed spacer region (NTS) of the ribosomal DNA. The
      pathogen of three other SWO cases was identified as T. rubrum. Direct physical
      contact between the subjects was unlikely because they were bedridden most of the
      time. Nine T. interdigitale strains were isolated from a bathtub used by patients
      on the floor with a high incidence of SWO alone, and all nine strains were D2II
      type, which suggests nosocomial infection. Consequently, the hospital infection
      control policy committee was consulted, bathing arrangements were changed, and
      nursing staff were educated about onychomycosis.

PMID- 28436563
TI  - An in vitro system for measuring genotoxicity mediated by human CYP3A4 in
      Saccharomyces cerevisiae.
AB  - P450 activity is required to metabolically activate many chemical carcinogens,
      rendering them highly genotoxic. CYP3A4 is the most abundantly expressed P450
      enzyme in the liver, accounting for most drug metabolism and constituting 50% of
      all hepatic P450 activity. CYP3A4 is also expressed in extrahepatic tissues,
      including the intestine. However, the role of CYP3A4 in activating chemical
      carcinogens into potent genotoxins is unclear. To facilitate efforts to determine
      whether CYP3A4, per se, can activate carcinogens into potent genotoxins, we
      expressed human CYP3A4 in the DNA-repair mutant (rad4 rad51) strain of budding
      yeast Saccharomyces cerevisiae and tested the novel, recombinant yeast strain for
      ability to report CYP3A4-mediated genotoxicity of a well-known genotoxin,
      aflatoxin B1 (AFB1 ). Yeast microsomes containing human CYP3A4, but not those
      that do not contain CYP3A4, were active in hydroxylation of diclofenac, a known
      CYP3A4 substrate drug, a result confirming CYP3A4 activity in the recombinant
      yeast strain. In cells exposed to AFB1 , the expression of CYP3A4 supported DNA
      adduct formation, chromosome rearrangements, cell death, and expression of the
      large subunit of ribonucleotide reductase, Rnr3, a marker of DNA damage.
      Expression of CYP3A4 also conferred sensitivity in rad4 rad51 mutants exposed to
      colon carcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). These
      data confirm the ability of human CYP3A4 to mediate the genotoxicity of AFB1 ,
      and illustrate the usefulness of the CYP3A4-expressing, DNA-repair mutant yeast
      strain for screening other chemical compounds that are CYP3A4 substrates, for
      potential genotoxicity. Environ. Mol. Mutagen. 58:217-227, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28436567
TI  - An ultrastructural study of chondroptosis: programmed cell death in degenerative
      intervertebral discs in vivo.
AB  - Apoptosis has been regarded to mediate intervertebral disc degeneration (IDD);
      however, the basic question of how the apoptotic bodies are cleared in the
      avascular intervertebral disc without phagocytes, which are essential to
      apoptosis, remains to be elucidated. Our goals were to investigate the
      ultrastructure of nucleus pulposus (NP) cells undergoing chondroptosis, a variant
      of apoptotic cell death, in a rabbit annular needle-puncture model of IDD.
      Experimental IDD was induced by puncturing discs with a 16-G needle in New
      Zealand rabbits. At 4 and 12 weeks after puncture, progressive degeneration was
      demonstrated by X-ray, magnetic resonance imaging and histological staining.
      TUNEL staining suggested a significant increase in the apoptosis index in the
      degenerated NP. However, the percentage of apoptotic cells with the classic
      ultrastructure morphology was much less than that with chondroptotic
      ultrastructure morphology under transmission electron microscopy (TEM). The
      chondroptotic cells from the early to late stage were visualized under TEM. In
      addition, the percentage of chondroptotic cells was significantly enhanced in the
      degenerated NP. Furthermore, 'paralyzed' cells were found in the herniated
      tissue. Western blotting revealed an increase in caspase3 expression in the
      degenerated NP. The expression of the Golgi protein (58K) was increased by the
      fourth week after puncture but decreased later. These findings indicate that
      chondroptosis is a major type of programmed cell death in the degenerated rabbit
      NP that may be related to the progressive development of IDD.

PMID- 28436566
TI  - Atrial fibrillation originating from superior vena cava with atrial flutter
      electrocardiogram pattern.
AB  - BACKGROUNDS: Substrate property is related to the genesis and maintenance of
      atrial fibrillation (AF). The aim of the study was to investigate the impact of
      substrate property on the electrocardiogram (ECG) in patients with AF originating
      from the superior vena cava (SVC). METHODS AND RESULTS: Seventy-six patients with
      AF originating from SVC who underwent catheter ablation were included from 2004
      to 2013. Of these patients, 16 had a presentation of atrial flutter (AFL)-pattern
      ECG during AF (group 1), and 60 patients did not (group 2). There was no
      significant difference in clinical characteristics between the groups. The
      percentage of low voltage zone (LVZ) in SVC below the level of pulmonary artery
      in group 1 was significantly larger than that in group 2. The polarities of the
      flutter wave in 12-lead ECG were compared with another 26 subjects with reverse
      typical AFL. The ECG morphology was characterized by negative or biphasic P waves
      in lead V1 in most of the patients in group 1 (62.5%), which was analogous to
      that in reverse typical AFL. The negative polarity of flutter waves in aVL might
      distinguish SVC AF with an AFL-pattern from reverse typical AFL. CONCLUSION: The
      ECG characteristics of AF originating from SVC can mimic atypical AFL. LVZ in the
      SVC may be associated with the presentation of AFL-pattern ECG.

PMID- 28436568
TI  - Effects of programmed teaching errors on acquisition and durability of self-care
      skills.
AB  - This investigation sheds light on necessary and sufficient conditions to
      establish self-care behavior chains among people with developmental disabilities.
      First, a descriptive assessment (DA) identified the types of teaching errors that
      occurred during self-care instruction. Second, the relative effects of three
      teaching errors observed during the DA were evaluated across two behavior chains
      for three participants. Third, the effects of individual teaching errors were
      studied with a third behavior chain per participant. Teaching errors included
      prompting steps out of order, delivering the reinforcer at times other than
      immediately following correct completion of the training step, and failing to
      prompt completion of all steps within a teaching trial. All teaching errors
      included in the evaluation interfered with skill acquisition and disrupted
      performance of mastered skills. Results are discussed in terms of future research
      on the components of efficacious treatment packages for disseminating effective
      practices.

PMID- 28436569
TI  - Association of waist circumference with outcomes in an acute general surgical
      unit.
AB  - BACKGROUND: Obesity prevalence is increasing in Australia, particularly in non
      metropolitan areas. The effect of obesity on acute surgical outcomes is not
      known. We aimed to record waist circumference (WC) (surrogate for obesity)
      amongst acute surgical unit (ASU) patients in a New South Wales regional
      hospital, and compare outcome measures (length of stay (LOS), unplanned return to
      theatre, readmission rates, intensive care unit (ICU) admission and mortality).
      METHODS: Retrospective cohort study of 4 months of consecutive ASU admissions,
      excluding age <16, pregnancy, out-of-area transfer and incomplete data. Patients
      were classified according to World Health Organization WC definitions as high
      risk or non-high-risk (increased-risk and no-risk). RESULTS: Of 695 admissions,
      512 met the inclusion criteria (47.1% female, average age 52.8 years (SD 22.3)),
      with 85.1% (P < 0.001) of females and 69.4% (P = 0.166) of males having an
      increased- or high-risk WC. This compares to rates amongst inner regional
      populations of 71.0% (female) and 66.4% (male). LOS was longer for high-risk
      patients (5.0 days versus 3.7 days, P = 0.002). However, the mean age of high
      risk patients was greater (56.6 years versus 46.9 years, P = 0.001) and LOS was
      longer for those aged >=60 (P < 0.001). After controlling for age, high-risk WC
      was not associated with any outcome measure, except amongst ICU admissions, where
      high-risk patients stayed longer (15.5 days versus 6.8 days, P < 0.001).
      CONCLUSION: Increased- and high-risk WC was overrepresented amongst female ASU
      patients. High-risk WC was associated with a significantly greater LOS in
      patients admitted to ICU. High-risk WC was not associated with other outcomes
      independent of age. WC is useful for quantifying obesity in the inpatient
      setting.

PMID- 28436571
TI  - Enantioselective Access to Robinson Annulation Products and Michael Adducts as
      Precursors.
AB  - The Robinson annulation is a reaction that has been useful for numerous syntheses
      since its discovery in 1935, especially in the field of steroid synthesis. The
      products are usually obtained after three consecutive steps: the formation of an
      enolate (or derivative), a conjugate addition, and an aldol reaction. Over the
      years, several methodological improvements have been made for each individual
      step or alternative routes have been devised to access the Robinson annulation
      products. The first part of this Review outlines the most relevant developments
      towards the formation of monocarbonyl-derived Robinson annulation products (MRA
      products, MRAPs) and activated monocarbonyl-derived Robinson annulation products
      (AMRA products, AMRAPs). The following sections are then devoted to the
      diastereoselective and enantioselective synthesis of these products, while the
      last section describes the enantiomeric resolution of racemic mixtures.

PMID- 28436570
TI  - Bre Enhances Osteoblastic Differentiation by Promoting the Mdm2-Mediated
      Degradation of p53.
AB  - Bre is a conserved cellular protein expressed in various tissues. Its major
      function includes DNA damage repair and anti-apoptosis. Recent studies indicate
      that Bre is potentially involved in stem cell differentiation although
      pathophysiological significance along with the molecular mechanisms is still
      unclear. Here, we report that Bre protein was substantially expressed in the bone
      tissue and its expression was highly upregulated during the osteogenic
      differentiation. To test a hypothesis that Bre plays functional roles in the
      process of osteogenic differentiation, we examined the expression of Bre in an
      osteoporosis mouse model. Compared with the normal bone tissue, Bre expression in
      osteoporotic bone was also significantly reduced. Moreover, knockdown of Bre in
      the mouse bone marrow mesenchymal cells significantly reduced the expression of
      osteogenic marker genes, the alkaline phosphatase activity, and the
      mineralization capacity, while overexpression of Bre greatly promoted the
      osteogenesis both in vitro and in vivo. Interestingly, we founded that knockdown
      of Bre led to activation of the p53 signaling pathways exhibited by increased
      p53, p21, and Mdm2. However, when we inhibited the p53 by siRNA silencing or
      pifithrin-alpha, the impaired osteogenesis caused by Bre knockdown was greatly
      restored. Finally, we found that Bre promoted the Mdm2-mediated p53
      ubiquitination and degradation by physically interacting with p53. Taken
      together, our results revealed a novel function of Bre in osteoblast
      differentiation through modulating the stability of p53. Stem Cells 2017;35:1760
      1772.

PMID- 28436573
TI  - Mapping Energy Levels for Organic Heterojunctions.
AB  - An organic semiconductor thin film is a solid-state matter comprising one or more
      molecules. For applications in electronics and photonics, several distinct
      functional organic thin films are stacked together to create a variety of devices
      such as organic light-emitting diodes and organic solar cells. The energy levels
      at these thin-film junctions dictate various electronic processes such as the
      charge transport across these junctions, the exciton dissociation rates at donor
      acceptor molecular interfaces, and the charge trapping during exciton formation
      in a host-dopant system. These electronic processes are vital to a device's
      performance and functionality. To uncover a general scientific principle in
      governing the interface energy levels, highest occupied molecular orbitals, and
      vacuum level dipoles, herein a comprehensive experimental research is conducted
      on several dozens of organic-organic heterojunctions representative of various
      device applications. It is found that the experimental data map on interface
      energy levels, after correcting variables such as molecular orientation-dependent
      ionization energies, consists of three distinct regions depending on interface
      fundamental physical parameters such as Fermi energy, work function, highest
      occupied molecular orbitals, and lowest unoccupied molecular orbitals. This
      general energy map provides a master guide in selection of new materials for
      fabricating future generations of organic semiconductor devices.

PMID- 28436572
TI  - A randomized, double-blind, placebo-controlled trial evaluating cysteamine in
      Huntington's disease.
AB  - BACKGROUND: Cysteamine has been demonstrated as potentially effective in numerous
      animal models of Huntington's disease. METHODS: Ninety-six patients with early
      stage Huntington's disease were randomized to 1200 mg delayed-release cysteamine
      bitartrate or placebo daily for 18 months. The primary end point was the change
      from baseline in the UHDRS Total Motor Score. A linear mixed-effects model for
      repeated measures was used to assess treatment effect, expressed as the least
      squares mean difference of cysteamine minus placebo, with negative values
      indicating less deterioration relative to placebo. RESULTS: At 18 months, the
      treatment effect was not statistically significant - least-squares mean
      difference, -1.5 +/- 1.71 (P = 0.385) - although this did represent less mean
      deterioration from baseline for the treated group relative to placebo. Treatment
      with cysteamine was safe and well tolerated. CONCLUSIONS: Efficacy of cysteamine
      was not demonstrated in this study population of patients with Huntington's
      disease. Post hoc analyses indicate the need for definitive future studies. (c)
      2017 International Parkinson and Movement Disorder Society.

PMID- 28436574
TI  - Severe infantile parkinsonism because of a de novo mutation on DLP1 mitochondrial
      peroxisomal protein.

PMID- 28436575
TI  - The Influence of First-Hand Testimony and Hearsay on Children's Belief in the
      Improbable.
AB  - Children (3.5-8.5 years; n = 105) heard claims about the occurrence of improbable
      or impossible events, then were asked whether the events could really happen.
      Some claims were based on informants' first-hand observations and others were
      hearsay. A baseline group (n = 56) reported their beliefs about these events
      without hearing testimony. Neither first-hand claims nor hearsay influenced
      beliefs about impossible events, which remained low across the age range. Hearsay
      (but not first-hand claims) did influence beliefs about improbable events.
      Preschoolers expressed greater belief following hearsay, compared to their
      beliefs following first-hand claims and compared to the baseline group's beliefs.
      By contrast, older children expressed less belief following hearsay, compared to
      their beliefs following first-hand claims and compared to the baseline group's
      beliefs.

PMID- 28436576
TI  - The role of macrophages in the pathogenesis of mycosis fungoides.
AB  - BACKGROUND: Macrophages are classified into classically activated (M1) and
      alternatively activated (M2) macrophages. Decrease in macrophage number in tumour
      tissue with treatment has been reported. AIM: The aim of this study was to
      determine whether treatment has an effect on the number of dermal M1 and M2
      macrophages in patients with mycosis fungoides (MF). METHODS: In total, 21
      patients (8 women, 13 men; age range 42-73 years) were included in this study. We
      determined markers for dermal M1 (inducible nitric oxide synthase and CD68) and
      M2 (markers: CD163 and CD206) macrophages using double immunohistochemistry to
      reduce the error rate, and then counted the cells. RESULTS: The number of dermal
      M1 cells was significantly lower pretreatment compared with post-treatment (P <
      0.01). The numbers of dermal M2 cells were also numerically decreased by
      treatment. These results did not change significantly after exclusion of the
      patients who had recurrence (n = 2). There were no statistically significant
      differences between groups classified by stage, lesion type or treatment outcome.
      CONCLUSION: Macrophage numbers are decreased in MF after treatment of tumour
      tissue.

PMID- 28436577
TI  - Reproducibility.

PMID- 28436578
TI  - Pruritic translucent papules, joint pains and giant cells.

PMID- 28436579
TI  - Infection-related mortality in Hispanic and non-Hispanic children with cancer.
AB  - BACKGROUND: Hispanic children with cancer experience poorer survival than their
      White counterparts. Infection is a known cause of cancer-related mortality;
      however, little is known about the risk of infection-related death among Hispanic
      children with cancer. We examine the association of Hispanic ethnicity with
      infection-related mortality and life-threatening events among children with
      cancer. PROCEDURE: For a cohort of all pediatric cancer patients diagnosed from
      1986 to 2012 and treated at a single tertiary care center, we obtained national
      death records to determine all-cause mortality and infection-related mortality,
      as well as intensive care unit (ICU) admissions as a surrogate for life
      threatening events. Cox proportional hazard models assessed all-cause mortality
      and infection-related mortality using ethnicity as the main independent variable.
      ICU admission rates were modeled using a zero-inflated Poisson regression model.
      Models were adjusted for gender, diagnosis year, age, residential location, and
      diagnosis. RESULTS: Of 6,198 patients, 741 (12%) were Hispanic. Mean follow-up
      was 11 years (SD = 8.04). There were 1,205 deaths, with 193 attributable to
      infection. Differences in all-cause mortality between Hispanic and non-Hispanic
      patients did not reach significance (hazard ratio [HR] = 1.14, 95% confidence
      interval [CI]: 0.96-1.36). However, Hispanic patients were 68% (HR = 1.68, 95%
      CI: 1.16-2.43) more likely to have an infection-related cause of death. Hispanic
      ethnicity was statistically associated with a higher rate of ICU admissions (rate
      ratio = 1.32, 95% CI: 1.12-1.56). CONCLUSION: Hispanic pediatric cancer patients
      were more likely to have an infection-related death and higher rates of ICU
      admissions than non-Hispanic patients. Infection may be an overlooked contributor
      to poorer outcomes among Hispanic patients.

PMID- 28436580
TI  - Pulmonary function and outcomes in infants randomized to a rescue course of
      antenatal steroids.
AB  - BACKGROUND/OBJECTIVE: Our objective was to obtain follow-up pulmonary function
      testing and assessment of clinical respiratory outcomes, at 1-2 years, in preterm
      infants whose mothers were randomized to a single rescue course of antenatal
      steroids (AS) versus placebo. METHODS: Follow-up of a randomized, double-blinded
      trial. In the original trial pregnant women >=14 days after initial course of AS
      were randomized to rescue AS or placebo. Pulmonary function testing and a
      standardized respiratory questionnaire were obtained at 1-2 years of corrected
      age. Respiratory compliance (Crs) was measured with the single-breath occlusion
      and functional residual capacity (FRC) with the nitrogen washout method. Analysis
      was by intention-to-treat. RESULTS: A total of 96 (87%) of available survivors
      were administered a respiratory questionnaire. Seventy-seven percent of available
      patients had pulmonary function testing performed. There was no significant
      difference between groups in incidence of wheezing, asthma, respiratory syncytial
      virus infection, respiratory readmissions, use of bronchodilators or other
      medications, or in measurements of pulmonary function. There was also no
      significant difference in corrected age at study, race, gender, or length at the
      time of pulmonary function testing. Infants in the rescue group had a comparable
      mean FRC (249.4 mL vs 246.2 mL; adjusted 95%CI for difference -15.45, 38.20; P =
      0.37) versus placebo. There were no differences in tidal volume or Crs.
      CONCLUSION: A rescue course of AS significantly increases Crs within 72 h of age
      and decreases oxygen need in newborn infants, without an adverse impact on
      pulmonary function or clinical respiratory outcomes at 1-2 years of age
      [NCT00669383].

PMID- 28436581
TI  - Pediatric acute lymphoblastic leukemia with t(1;19)/TCF3-PBX1 in Taiwan.
AB  - BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3)
      with TCF3-PBX1 fusion is one of the most frequent translocations. Historically,
      it has been associated with poor prognosis. Intensive treatment, however, has
      improved its outcome. We determined the outcome of children with this genotype
      treated with contemporary intensive chemotherapy in Taiwan. PROCEDURE: In Taiwan
      Pediatric Oncology Group 2002 ALL studies, genotypes were determined by
      cytogenetic analysis and/or reverse transcriptase polymerase chain reaction
      assay. Based on presenting features, immunophenotype and genotype, patients were
      assigned to one of the three risk groups: standard risk (SR), high risk (HR), or
      very high risk (VHR). The patients with t(1;19)/TCF3-PBX1 were treated in the HR
      arm receiving more intensive chemotherapy. The outcomes of patients with
      t(1;19)/TCF3-PBX1 were compared to that of patients with other subtypes of B
      precursor ALL (B-ALL). RESULTS: Of the 1,129 patients with B-ALL, 64 (5.7%) had
      t(1;19)/TCF3-PBX1; 51 of whom were treated in the HR arm, but 11 were treated in
      the VHR and 2 in the SR arm because of physician's preference. As a group, 64
      patients with t(1;19)/TCF3-PBX1 had similar 5-year event-free survival (83.3 +/-
      4.8%) as those with TEL-AML1 (85.2 +/- 3.4%, P = 0.984) or those with
      hyperdiploidy >50 (84.0 +/- 3.1%, P = 0.748). The cumulative risk of any
      (isolated plus combined) central nervous system relapse among patients with
      t(1;19)/TCF3-PBX1 (8.7 +/- 3.8%) tended to be higher than that of patients with
      TEL-AML1 (5.8 +/- 2.3%, P = 0.749) or those with hyperdiploidy (4.1 +/- 1.8%, P =
      0.135), albeit the differences did not reach statistical significance.
      CONCLUSIONS: With contemporary intensive chemotherapy, children with t(1;19)/TCF3
      PBX1 fared as well as those with favorable genotypes (TEL-AML1 or hyperdiploidy).

PMID- 28436582
TI  - Phase I study of bortezomib in combination with irinotecan in patients with
      relapsed/refractory high-risk neuroblastoma.
AB  - PURPOSE: Prognosis for relapsed/refractory high-risk neuroblastoma (HR-NBL)
      remains poor. Bortezomib, a proteasome inhibitor, has shown preclinical activity
      against NBL as a single agent and in combination with cytotoxic chemotherapy
      including irinotecan. PATIENTS AND METHODS: Eighteen HR-NBL patients with primary
      refractory (n = 8) or relapsed (n = 10) disease were enrolled in a Phase I study
      using modified Time To Event Continual Reassessment Method. Bortezomib (1.2 mg/m2
      /day) was administered on days 1, 4, 8, and 11 intravenously (IV) and irinotecan
      was given IV on days 1-5 (35, 40, or 45 mg/m2 /day, on dose levels [DL] 1-3,
      respectively). The maximum tolerated dose (MTD), dose-limiting toxicity (DLT),
      and response rate were examined. RESULTS: Eighteen NBL patients were evaluable
      for toxicity; 17 were evaluable for response assessment. A total of 142 courses
      were delivered (mean 8.2, median 2, range 1-48), with two patients receiving more
      than 40 courses of therapy. Two DLTs were reported, including a grade 4
      thrombocytopenia (DL2) and a grade 3 irritability (DL3). MTD was estimated as
      DL3. Two of 17 (12%) evaluable patients showed objective responses (ORs) lasting
      more than 40 courses, including 1 partial remission and 1 complete remission.
      Four patients (23%) had prolonged stable disease (SD) lasting six or more
      courses, with a total of 35% study patients demonstrating clinical benefit in the
      form of prolonged OR or SD. CONCLUSION: The combination of bortezomib and
      irinotecan was well tolerated by patients with relapsed/refractory NBL with
      favorable toxicity profile. It also showed modest but promising clinical activity
      and merits further testing in Phase II studies.

PMID- 28436584
TI  - Exploring possible reaction pathways for the o-atom transfer reactions to
      unsaturated substrates catalyzed by a [Ni-NO2 ] <-> [Ni-NO] redox couple using
      DFT methods.
AB  - The (nitro)(N-methyldithiocarbamato)(trimethylphospane)nickel(II), [Ni(NO2 )(S2
      CNHMe)(PMe3 )] complex catalyses efficiently the O-atom transfer reactions to CO
      and acetylene. Energetically feasible sequence of elementary steps involved in
      the catalytic cycle of the air oxidation of CO and acetylene are proposed
      promoted by the Ni(NO2 )(S2 CNHMe)(PMe3 )] <-> Ni(NO2 )(S2 CNHMe)(PMe3 ) redox
      couple using DFT methods both in vacuum and dichloromethane solutions. The
      catalytic air oxidation of HC=CH involves formation of a five-member metallacycle
      intermediate, via a [3 + 2] cyclo-addition reaction of HC=CH to the Ni-N = O
      moiety of the Ni(NO2 )(S2 CNHMe)(PMe3 )] complex, followed by a beta H-atom
      migration toward the Calpha carbon atom of the coordinated acetylene and release
      of the oxidation product (ketene). The geometric and energetic reaction profile
      for the reversible [Ni( kappaN1-NO2 )(S2 CNHMe)(PMe3 )] ? [Ni( kappaO,O2-ONO)(S2
      CNHMe)(PMe3 )] linkage isomerization has also been modeled by DFT calculations.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28436583
TI  - Physical activity and exercise for chronic pain in adults: an overview of
      Cochrane Reviews.
AB  - BACKGROUND: Chronic pain is defined as pain lasting beyond normal tissue healing
      time, generally taken to be 12 weeks. It contributes to disability, anxiety,
      depression, sleep disturbances, poor quality of life, and healthcare costs.
      Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the
      treatment choice for chronic pain included recommendations for rest and
      inactivity. However, exercise may have specific benefits in reducing the severity
      of chronic pain, as well as more general benefits associated with improved
      overall physical and mental health, and physical functioning.Physical activity
      and exercise programmes are increasingly being promoted and offered in various
      healthcare systems, and for a variety of chronic pain conditions. It is therefore
      important at this stage to establish the efficacy and safety of these programmes,
      and furthermore to address the critical factors that determine their success or
      failure. OBJECTIVES: To provide an overview of Cochrane Reviews of adults with
      chronic pain to determine (1) the effectiveness of different physical activity
      and exercise interventions in reducing pain severity and its impact on function,
      quality of life, and healthcare use; and (2) the evidence for any adverse effects
      or harm associated with physical activity and exercise interventions. METHODS: We
      searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane
      Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled
      trials (RCTs), after which we tracked any included reviews for updates, and
      tracked protocols in case of full review publication until an arbitrary cut-off
      date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological
      quality of the reviews using the AMSTAR tool, and also planned to analyse data
      for each painful condition based on quality of the evidence.We extracted data for
      (1) self-reported pain severity, (2) physical function (objectively or
      subjectively measured), (3) psychological function, (4) quality of life, (5)
      adherence to the prescribed intervention, (6) healthcare use/attendance, (7)
      adverse events, and (8) death.Due to the limited data available, we were unable
      to directly compare and analyse interventions, and have instead reported the
      evidence qualitatively. MAIN RESULTS: We included 21 reviews with 381 included
      studies and 37,143 participants. Of these, 264 studies (19,642 participants)
      examined exercise versus no exercise/minimal intervention in adults with chronic
      pain and were used in the qualitative analysis.Pain conditions included
      rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent
      claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury,
      postpolio syndrome, and patellofemoral pain. None of the reviews assessed
      'chronic pain' or 'chronic widespread pain' as a general term or specific
      condition. Interventions included aerobic, strength, flexibility, range of
      motion, and core or balance training programmes, as well as yoga, Pilates, and
      tai chi.Reviews were well performed and reported (based on AMSTAR), and included
      studies had acceptable risk of bias (with inadequate reporting of attrition and
      reporting biases). However the quality of evidence was low due to participant
      numbers (most included studies had fewer than 50 participants in total), length
      of intervention and follow-up (rarely assessed beyond three to six months). We
      pooled the results from relevant reviews where appropriate, though results should
      be interpreted with caution due to the low quality evidence. Pain severity:
      several reviews noted favourable results from exercise: only three reviews that
      reported pain severity found no statistically significant changes in usual or
      mean pain from any intervention. However, results were inconsistent across
      interventions and follow-up, as exercise did not consistently bring about a
      change (positive or negative) in self-reported pain scores at any single point.
      Physical function: was the most commonly reported outcome measure. Physical
      function was significantly improved as a result of the intervention in 14
      reviews, though even these statistically significant results had only small-to
      moderate effect sizes (only one review reported large effect sizes).
      Psychological function and quality of life: had variable results: results were
      either favourable to exercise (generally small and moderate effect size, with two
      reviews reporting significant, large effect sizes for quality of life), or showed
      no difference between groups. There were no negative effects. Adherence to the
      prescribed intervention: could not be assessed in any review. However, risk of
      withdrawal/dropout was slightly higher in the exercising group (82.8/1000
      participants versus 81/1000 participants), though the group difference was non
      significant. Healthcare use/attendance: was not reported in any review. Adverse
      events, potential harm, and death: only 25% of included studies (across 18
      reviews) actively reported adverse events. Based on the available evidence, most
      adverse events were increased soreness or muscle pain, which reportedly subsided
      after a few weeks of the intervention. Only one review reported death separately
      to other adverse events: the intervention was protective against death (based on
      the available evidence), though did not reach statistical significance. AUTHORS'
      CONCLUSIONS: The quality of the evidence examining physical activity and exercise
      for chronic pain is low. This is largely due to small sample sizes and
      potentially underpowered studies. A number of studies had adequately long
      interventions, but planned follow-up was limited to less than one year in all but
      six reviews.There were some favourable effects in reduction in pain severity and
      improved physical function, though these were mostly of small-to-moderate effect,
      and were not consistent across the reviews. There were variable effects for
      psychological function and quality of life.The available evidence suggests
      physical activity and exercise is an intervention with few adverse events that
      may improve pain severity and physical function, and consequent quality of life.
      However, further research is required and should focus on increasing participant
      numbers, including participants with a broader spectrum of pain severity, and
      lengthening both the intervention itself, and the follow-up period.

PMID- 28436585
TI  - The mobile conjugate reinforcement paradigm in a lab setting.
AB  - The mobile conjugate reinforcement task was administered to 4-month-old infants
      in a lab rather than a home setting where it is usually administered. Learning
      and retention patterns were comparable to those of infants tested in their homes,
      suggesting flexibility in where this task can be administered. These results pave
      the way for this task to be used with a broader range of infants for whom home
      visits are not practical or convenient (e.g., infants in child care).
      Developmental research conducted with a more diverse population of infants would
      facilitate our understanding of cognitive development very early in life.

PMID- 28436586
TI  - Transesophageal and invasive electrophysiologic evaluation in children with Wolff
      Parkinson-White pattern.
AB  - BACKGROUND: Risk stratification for Wolff-Parkinson-White (WPW) pattern either by
      noninvasive or invasive tests is important to determine whether an ablation is
      necessary or not. The aim was to compare noninvasive tests and invasive studies
      in a pediatric WPW population. METHODS: A total of 71 WPW patients (median age 14
      years [interquartile range, 11-16 years]; 43 male) underwent Holter monitoring,
      exercise stress test (EST), and transesophageal electrophysiological study
      (TEEPS). In the case of a <=270-ms effective refractory period of accessory
      pathway or induction of supraventricular tachycardia using TEEPS, patients were
      classified as high risk and underwent invasive electrophysiological study (EPS).
      RESULTS: Nine of 23 patients with low risk by Holter and eight of 26 patients
      with low risk by EST had high risk in TEEPS. Risky TEEPS results were detected in
      42 of 71 patients and those patients underwent EPS. High-risk characteristic in
      EPS was detected in seven of nine patients with low risk by Holter and in seven
      of eight with low risk by EST. Both tests yielded moderate specificity (52-69%)
      and negative predictive value (61-69%) according to TEEPS. CONCLUSION: Holter and
      EST have low predictive value in WPW risk stratification. However, TEEPS and EPS
      are extremely valuable in WPW risk stratification. TEEPS may reveal important and
      useful results for WPW risk determination, especially in small children not
      having undergone EPS in order to avoid its complications.

PMID- 28436587
TI  - Coparenting Conflict and Academic Readiness in Children of Teen Mothers:
      Effortful Control as a Mediator.
AB  - Children's exposure to coparenting conflict has important implications for their
      developmental functioning, yet limited work has focused on such processes in
      families with diverse structures or ethnically and culturally diverse
      backgrounds. This longitudinal study examined the processes by which Mexican
      origin adolescent mothers' coparenting conflict with their 3-year-old children's
      grandmothers and biological fathers (N = 133 families) were linked to children's
      academic and social skills at 5 years of age, and whether children's effortful
      control at 4 years of age mediated the link between coparenting conflict and
      indices of children's academic readiness. Findings revealed that adolescent
      mothers' coparenting conflict with their child's biological father was linked to
      indices of children's academic and social school readiness through children's
      effortful control among girls, but not boys, whereas conflict with grandmothers
      was directly linked to boys' and girls' social functioning 2 years later.
      Findings offer information about different mechanisms by which multiple
      coparenting units in families of adolescent mothers are related to their
      children's outcomes, and this work has important implications for practitioners
      working with families of adolescent mothers.

PMID- 28436589
TI  - Short-chain fatty acids augment rat duodenal mucosal barrier function.
AB  - NEW FINDINGS: What is the central question of this study? Small intestinal
      epithelium is exposed to high concentrations of short-chain fatty acids (SCFAs),
      but their role in regulating intestinal mucosal barrier function and motility is
      not fully understood. What is the main finding and its importance? By perfusing
      the duodenal segment in anaesthetized rats, we show that acetate and propionate
      significantly decrease mucosal paracellular permeability and transepithelial net
      fluid flux and increase mucosal bicarbonate secretion. Likewise, SCFAs
      administered i.v. decrease mucosal permeability but decrease bicarbonate
      secretion. Altered luminal chemosensing or aberrant signalling in response to
      SCFAs might contribute to symptoms observed in patients with suppressed mucosal
      barrier function. Short-chain fatty acids (SCFAs) are produced by bacterial
      fermentation in the large intestine, particularly from diets containing fibres
      and carbohydrates. The small intestinal epithelium is exposed to SCFAs derived
      mainly from oral bacteria or food supplementation. Although luminal nutrients are
      important in regulation of intestinal functions, the role of SCFAs in regulation
      of small intestinal mucosal barrier function and motility has not been fully
      described. The aim of the present study was to elucidate the effects of acetate
      and propionate on duodenal mucosal barrier function and motility. Rats were
      anaesthetized with thiobarbiturate, and a 30 mm segment of proximal duodenum with
      an intact blood supply was perfused. The effects on duodenal bicarbonate
      secretion, blood-to-lumen clearance of 51 Cr-EDTA, motility and transepithelial
      net fluid flux were investigated. Perfusion of the duodenum with acetate or
      propionate significantly decreased mucosal paracellular permeability and
      transepithelial net fluid flux and significantly increased bicarbonate secretion.
      Acetate or propionate administered as an i.v. infusion decreased the mucosal
      paracellular permeability, but significantly decreased bicarbonate secretion.
      Luminal SCFAs changed the duodenal motility pattern from migrating motor
      complexes to fed patterns. Systemic administration of glucagon-like peptide-2
      induced increases in both bicarbonate secretion and net fluid absorption, but did
      not change motility. Glucagon-like peptide-2 infusion during luminal perfusion of
      SCFAs significantly reduced the motility. In conclusion, SCFAs decreased duodenal
      paracellular permeability and net fluid flux. Short-chain fatty acids induced
      opposite effects on bicarbonate secretion after luminal and i.v. administration.
      Presence of SCFAs in the lumen induces fed motility patterns. Altered luminal
      chemosensing and aberrant signalling in response to SCFAs might contribute to
      symptoms observed in patients with suppressed barrier function.

PMID- 28436590
TI  - Identification of small molecules using accurate mass MS/MS search.
AB  - Tandem mass spectral library search (MS/MS) is the fastest way to correctly
      annotate MS/MS spectra from screening small molecules in fields such as
      environmental analysis, drug screening, lipid analysis, and metabolomics. The
      confidence in MS/MS-based annotation of chemical structures is impacted by
      instrumental settings and requirements, data acquisition modes including data
      dependent and data-independent methods, library scoring algorithms, as well as
      post-curation steps. We critically discuss parameters that influence search
      results, such as mass accuracy, precursor ion isolation width, intensity
      thresholds, centroiding algorithms, and acquisition speed. A range of publicly
      and commercially available MS/MS databases such as NIST, MassBank, MoNA,
      LipidBlast, Wiley MSforID, and METLIN are surveyed. In addition, software tools
      including NIST MS Search, MS-DIAL, Mass Frontier, SmileMS, Mass++, and XCMS2 to
      perform fast MS/MS search are discussed. MS/MS scoring algorithms and challenges
      during compound annotation are reviewed. Advanced methods such as the in silico
      generation of tandem mass spectra using quantum chemistry and machine learning
      methods are covered. Community efforts for curation and sharing of tandem mass
      spectra that will allow for faster distribution of scientific discoveries are
      discussed.

PMID- 28436588
TI  - Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.
AB  - ERG, an ETS family transcription factor frequently overexpressed in human
      leukemia, has been implicated as a key regulator of hematopoietic stem cells.
      However, how ERG controls normal hematopoiesis, particularly at the stem and
      progenitor cell level, and how it contributes to leukemogenesis remain
      incompletely understood. Using homologous recombination, we generated an Erg
      knockdown allele (Ergkd ) in which Erg expression can be conditionally restored
      by Cre recombinase. Ergkd/kd animals die at E10.5-E11.5 due to defects in
      endothelial and hematopoietic cells, but can be completely rescued by Tie2-Cre
      mediated restoration of Erg in these cells. In Ergkd/+ mice, ~40% reduction in
      Erg dosage perturbs both fetal liver and bone marrow hematopoiesis by reducing
      the numbers of Lin- Sca-1+ c-Kit+ (LSK) hematopoietic stem and progenitor cells
      (HSPCs) and megakaryocytic progenitors. By genetic mosaic analysis, we find that
      Erg-restored HSPCs outcompete Ergkd/+ HSPCs for contribution to adult
      hematopoiesis in vivo. This defect is in part due to increased apoptosis of HSPCs
      with reduced Erg dosage, a phenotype that becomes more drastic during 5-FU
      induced stress hematopoiesis. Expression analysis reveals that reduced Erg
      expression leads to changes in expression of a subset of ERG target genes
      involved in regulating survival of HSPCs, including increased expression of a pro
      apoptotic regulator Bcl2l11 (Bim) and reduced expression of Jun. Collectively,
      our data demonstrate that ERG controls survival of HSPCs, a property that may be
      used by leukemic cells. Stem Cells 2017;35:1773-1785.

PMID- 28436591
TI  - Ammonia Oxide as a Building Block for High-Performance and Insensitive Energetic
      Materials.
AB  - 3,5-Dinitrimino-1,2,4-triazole (2) with three protons has the potential of
      deprotonation to form energetic salts. Neutralization of 2 with 50 %
      hydroxylamine in varying molar ratios leads to the formation of the corresponding
      mono/dihydroxylammonium energetic salts. Additionally compound 5, an ammonia
      oxide adduct of dihydroxylammonium 3,5-dinitramino-1,2,4-triazolate, was prepared
      when excess hydroxylamine was used. The structures of 3-5 are supported by single
      crystal X-ray diffraction. The energetic properties of the new materials are
      competitive. Utilization of ammonia oxide adducts in hydroxylammonium energetic
      salts could lead to future practical applications as energetic materials.

PMID- 28436592
TI  - Diagnostic Value of Virtual Touch Tissue Imaging Quantification for Evaluating
      Median Nerve Stiffness in Carpal Tunnel Syndrome.
AB  - OBJECTIVES: To measure the shear wave velocity (SWV) of the median nerve by
      Virtual Touch tissue imaging quantification (VTIQ; Siemens AG, Erlangen, Germany)
      through the beginning of the carpal tunnel and to determine whether VTIQ could be
      used to diagnose carpal tunnel syndrome. METHODS: This study recruited 49
      consecutive patients (72 wrists) with a definitive diagnosis of carpal tunnel
      syndrome and 23 healthy volunteers (46 wrists). We measured the median nerve
      diameter and cross-sectional area by 2-dimensional sonography and the SWV by
      VTIQ. The interobserver variability was analyzed, and diagnostic values were
      evaluated by drawing a receiver operating characteristic curve. RESULTS: The
      median nerve SWV was significantly higher in the carpal tunnel syndrome group
      (3.857 m/s) than the control group (2.542 m/s; P < .05). A 3.0-m/s SWV cutoff
      value revealed sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of 83.3%, 91.3%, 93.8%, 77.8%, and 86.4%,
      respectively. The interobserver agreement was excellent for the SWV measurements.
      CONCLUSIONS: The median nerve SWV at the carpal tunnel inlet is significantly
      higher in patients with carpal tunnel syndrome, for whom VTIQ appears to be a
      highly reproducible diagnostic technique.

PMID- 28436593
TI  - Results for patients with sarcoma not otherwise specified and other diagnoses
      than Ewing sarcoma treated according to the Euro-EWING 99 trial.
AB  - BACKGROUND: Euro-EWING 99 trial of the European Ewing tumor Working Initiative of
      National Groups (EE99) was an international phase III study in patients with
      Ewing sarcoma. The German Society of Pediatric Oncology and Hematology (GPOH)
      data center registered and followed patients with other diagnoses than Ewing
      sarcoma who were treated according to the EE99 protocol in an additional non
      Ewing database. PROCEDURE: Data of 27 patients with other diagnoses than Ewing
      sarcoma treated according to the EE99 protocol were analyzed. Patients had
      miscellaneous histologic diagnoses, the majority were diagnosed with sarcoma not
      otherwise specified (NOS) arising in bone and soft tissue (63%). RESULTS: The
      median age at diagnosis was 16.9 years (range 4.5-41.4). Localized disease was
      diagnosed in 61.5% of the patients and 38.5% had distant metastases at time of
      primary diagnosis. The median follow-up time was 3.7 years (range 0.5-9.5).
      Patients with localized disease showed a 3-year event-free survival (EFS) of 68%,
      compared to 3-year EFS of 20% in patients with metastases (P = 0.042). Three-year
      EFS for patients with sarcoma NOS was 52%, patients with localized and metastatic
      disease showed 3-year EFS of 66 and 20%, respectively. CONCLUSION: EFS in
      patients with other diagnoses than Ewing sarcoma treated according to EE99 was
      significantly higher in patients with localized than metastatic disease. Sarcomas
      of soft tissue and bone that cannot be classified to current diagnostic
      categories constitute a therapeutic challenge.

PMID- 28436594
TI  - Cassandra: An open source Monte Carlo package for molecular simulation.
AB  - Cassandra is an open source atomistic Monte Carlo software package that is
      effective in simulating the thermodynamic properties of fluids and solids. The
      different features and algorithms used in Cassandra are described, along with
      implementation details and theoretical underpinnings to various methods used.
      Benchmark and example calculations are shown, and information on how users can
      obtain the package and contribute to it are provided. (c) 2017 Wiley Periodicals,
      Inc.

PMID- 28436595
TI  - Isolated intracerebral Langerhans cell histiocytosis with multifocal lesions.

PMID- 28436596
TI  - Very late-onset pure autonomic failure.

PMID- 28436597
TI  - Glycan Analysis by Ion Mobility-Mass Spectrometry.
AB  - Carbohydrates form one of the major classes of biological macromolecules in
      living organisms. To investigate their properties and function, an in-depth
      knowledge of their underlying structure is essential. However, the inherent
      structural complexity of glycans represents a major challenge. Carbohydrates are
      often branched and exhibit diverse regio- and stereochemistry. This in turn leads
      to a vast number of possible isomers, which are difficult to distinguish by using
      established analytical tools. In the last decade, ion mobility-mass spectrometry,
      a technique that separates ions based on their mass, charge, size, and shape, has
      emerged as a powerful alternative for isomer distinction. This Minireview
      highlights recent advances in ion mobility-mass spectrometry of complex
      carbohydrates and discusses its role in future analysis workflows.

PMID- 28436598
TI  - The expression of Helicobacter pylori tfs plasticity zone cluster is regulated by
      pH and adherence, and its composition is associated with differential gastric IL
      8 secretion.
AB  - BACKGROUND: Helicobacter pylori virulence is associated with different clinical
      outcomes. The existence of an intact dupA gene from tfs4b cluster has been
      suggested as a predictor for duodenal ulcer development. However, the role of tfs
      plasticity zone clusters in the development of ulcers remains unclear. We studied
      several H. pylori strains to characterize the gene arrangement of tfs3 and tfs4
      clusters and their impact in the inflammatory response by infected gastric cells.
      METHODS: The genome of 14 H. pylori strains isolated from Western patients,
      pediatric (n=10) and adult (n=4), was fully sequenced using the Illumina platform
      MiSeq, in addition to eight pediatric strains previously sequenced. These strains
      were used to infect human gastric cells, and the secreted interleukin-8 (IL-8)
      was quantified by ELISA. The expression of virB2, dupA, virB8, virB10, and virB6
      was assessed by quantitative PCR in adherent and nonadherent fractions of H.
      pylori during in vitro co-infection, at different pH values. RESULTS: We have
      found that cagA-positive H. pylori strains harboring a complete tfs plasticity
      zone cluster significantly induce increased production of IL-8 from gastric
      cells. We have also found that the region spanning from virB2 to virB10 genes
      constitutes an operon, whose expression is increased in the adherent fraction of
      bacteria during infection, as well as in both adherent and nonadherent fractions
      at acidic conditions. CONCLUSIONS: A complete tfs plasticity zone cluster is a
      virulence factor that may be important for the colonization of H. pylori and to
      the development of severe outcomes of the infection with cagA-positive strains.

PMID- 28436599
TI  - Metformin as targeted treatment in fragile X syndrome.
AB  - BACKGROUND: Individuals with fragile X syndrome (FXS) have both behavioral and
      medical comorbidities and the latter include obesity in approximately 30% and the
      Prader-Willi Phenotype (PWP) characterized by severe hyperphagia and morbid
      obesity in less than 10%. Metformin is a drug used in individuals with type 2
      diabetes, obesity or impaired glucose tolerance and it has a strong safety
      profile in children and adults. Recently published studies in the Drosophila
      model and the knock out mouse model of FXS treated with metformin demonstrate the
      rescue of multiple phenotypes of FXS. MATERIALS AND METHODS: We present 7 cases
      of individuals with FXS who have been treated with metformin clinically. One case
      with type 2 diabetes, 3 cases with the PWP, 2 adults with obesity and/or
      behavioral problems and, a young child with FXS. These individuals were
      clinically treated with metformin and monitored for behavioral changes with the
      Aberrant Behavior Checklist and metabolic changes with a fasting glucose and
      HgbA1c. RESULTS: We found consistent improvements in irritability, social
      responsiveness, hyperactivity, and social avoidance, in addition to comments from
      the family regarding improvements in language and conversational skills. No
      significant side-effects were noted and most patients with obesity lost weight.
      CONCLUSION: We recommend a controlled trial of metformin in those with FXS.
      Metformin appears to be an effective treatment of obesity including those with
      the PWP in FXS. Our study suggests that metformin may also be a targeted
      treatment for improving behavior and language in children and adults with FXS.

PMID- 28436600
TI  - High-Performance Integrated Self-Package Flexible Li-O2 Battery Based on Stable
      Composite Anode and Flexible Gas Diffusion Layer.
AB  - With the rising development of flexible and wearable electronics, corresponding
      flexible energy storage devices with high energy density are required to provide
      a sustainable energy supply. Theoretically, rechargeable flexible Li-O2 batteries
      can provide high specific energy density; however, there are only a few reports
      on the construction of flexible Li-O2 batteries. Conventional flexible Li-O2
      batteries possess a loose battery structure, which prevents flexibility and
      stability. The low mechanical strength of the gas diffusion layer and anode also
      lead to a flexible Li-O2 battery with poor mechanical properties. All these
      attributes limit their practical applications. Herein, the authors develop an
      integrated flexible Li-O2 battery based on a high-fatigue-resistance anode and a
      novel flexible stretchable gas diffusion layer. Owing to the synergistic effect
      of the stable electrocatalytic activity and hierarchical 3D interconnected
      network structure of the free-standing cathode, the obtained flexible Li-O2
      batteries exhibit superior electrochemical performance, including a high specific
      capacity, an excellent rate capability, and exceptional cycle stability.
      Furthermore, benefitting from the above advantages, the as-fabricated flexible
      batteries can realize excellent mechanical and electrochemical stability. Even
      after a thousand cycles of the bending process, the flexible Li-O2 battery can
      still possess a stable open-circuit voltage, a high specific capacity, and a
      durable cycle performance.

PMID- 28436601
TI  - Management of skin adverse events associated with immune checkpoint inhibitors in
      patients with melanoma: A nursing perspective.
AB  - PURPOSE: Immune checkpoint inhibitors are associated with a unique immune-related
      side effect profile that requires prompt recognition and management. Skin
      toxicities are the most common, and often earliest occurring, drug-related
      adverse events (AEs) of any grade observed upon treatment with these agents. The
      purpose of this review is to provide practical guidance on the identification and
      treatment of skin AEs associated with the immune checkpoint inhibitors
      (ipilimumab, nivolumab, and pembrolizumab) from a nursing perspective, and
      demonstrate hands-on application of the guidance using relevant patient case
      studies. DATA SOURCES: Data for drug-related skin AEs were summarized from phase
      3 nivolumab and nivolumab + ipilimumab trials and phase 2 and 3 pembrolizumab
      trials. Patient case studies were provided by the lead (M.T.) and senior (J.N.C.)
      authors. CONCLUSIONS: The recommendations presented here, based on accumulated
      clinical trial and clinical practice experience are consistent with established
      treatment guidelines and reach beyond established guidelines and recommendations
      for the management of AEs associated with immune checkpoint inhibitors.
      IMPLICATIONS FOR PRACTICE: The practical treatment guidance presented here may
      help familiarize medical teams with the recognition and management of skin AEs
      associated with these recently approved agents. The enclosed recommendations may
      contribute to optimized treatment through awareness of typical time to onset and
      clinical presentation, knowledge of management options, and appropriate
      application of treatment.

PMID- 28436602
TI  - Accuracy of circulating histones in predicting persistent organ failure and
      mortality in patients with acute pancreatitis.
AB  - BACKGROUND: Early prediction of acute pancreatitis severity remains a challenge.
      Circulating levels of histones are raised early in mouse models and correlate
      with disease severity. It was hypothesized that circulating histones predict
      persistent organ failure in patients with acute pancreatitis. METHODS:
      Consecutive patients with acute pancreatitis fulfilling inclusion criteria
      admitted to Royal Liverpool University Hospital were enrolled prospectively
      between June 2010 and March 2014. Blood samples were obtained within 48 h of
      abdominal pain onset and relevant clinical data during the hospital stay were
      collected. Healthy volunteers were enrolled as controls. The primary endpoint was
      occurrence of persistent organ failure. The predictive values of circulating
      histones, clinical scores and other biomarkers were determined. RESULTS: Among
      236 patients with acute pancreatitis, there were 156 (66.1 per cent), 57 (24.2
      per cent) and 23 (9.7 per cent) with mild, moderate and severe disease
      respectively, according to the revised Atlanta classification. Forty-seven
      healthy volunteers were included. The area under the receiver operating
      characteristic (ROC) curve (AUC) for circulating histones in predicting
      persistent organ failure and mortality was 0.92 (95 per cent c.i. 0.85 to 0.99)
      and 0.96 (0.92 to 1.00) respectively; histones were at least as accurate as
      clinical scores or biochemical markers. For infected pancreatic necrosis and/or
      sepsis, the AUC was 0.78 (0.62 to 0.94). Histones did not predict or correlate
      with local pancreatic complications, but correlated negatively with leucocyte
      cell viability (r = -0.511, P = 0.001). CONCLUSION: Quantitative assessment of
      circulating histones in plasma within 48 h of abdominal pain onset can predict
      persistent organ failure and mortality in patients with acute pancreatitis. Early
      death of immune cells may contribute to raised circulating histone levels in
      acute pancreatitis.

PMID- 28436603
TI  - Parent perception of the impact of using thickened fluids in children with
      dysphagia.
AB  - BACKGROUND: Oropharyngeal dysphagia occurs in children without known neurological
      disorders, increasing their risk for respiratory problems and inadequate intake.
      Clinicians may recommend thickening nutritive fluids; however, there is little
      research regarding the impact of thickening nutritive fluids on clinical outcomes
      in children. METHODS: We used a parental reporting tool to determine whether
      parents identified changes in signs of dysphagia or volume of intake when
      thickened fluids were incorporated into an individualized feeding program for
      dysphagic children without known neurological problems. Fifty-five children
      diagnosed with dysphagia, for whom thickened fluids had been recommended per
      radiographic and clinical exam, qualified for the study. Parents of 44 children
      (24 females, 20 males) aged 2 weeks to 14 months completed baseline and post
      thickening (within 90 days) rating scales. RESULTS: Compared to baseline, parents
      reported significant decreases in the frequency of apnea (W = -219, P < 0.0001, r
      = 0.399), congestion (W = -450, P < 0.0001, r = 0.579), coughing/choking with
      drinking (W = -485, P < 0.0001, r = 0.603), resistance to feeding (W = -344.5, P
      < 0.0001, r = 0.476), vomiting during feeding (W = -409, P < 0.0001, r = 0.565),
      and wheezing (W = -337, P < 0.001, r = 0.449). For those children whose parents
      initially reported inadequate levels of intake, there was a significant (Z =
      3.15, P = 0.0029, r = 0.47) increase (+49.63 mm) in the rated adequacy of liquid
      intake, as well as a significant increase (+1.41 oz.) in the estimated volume per
      feeding (Z = 224, P = 0.29, r = 0.33). CONCLUSION: These results provide
      information for clinicians and physicians to incorporate when considering the use
      of thickened fluids in the dysphagia management of children without a known
      neurological diagnosis.

PMID- 28436604
TI  - Solvent-Free Mechanochemical Synthesis of Nitrogen-Doped Nanoporous Carbon for
      Electrochemical Energy Storage.
AB  - Nitrogen-doped nanoporous carbons were synthesized by a solvent-free
      mechanochemically induced one-pot synthesis. This facile approach involves the
      mechanochemical treatment and carbonization of three solid materials: potassium
      carbonate, urea, and lignin, which is a waste product from pulp industry. The
      resulting nitrogen-doped porous carbons offer a very high specific surface area
      up to 3000 m2  g-1 and large pore volume up to 2 cm3  g-1 . The mechanochemical
      reaction and the impact of activation and functionalization are investigated by
      nitrogen and water physisorption and high-resolution X-ray photoelectron
      spectroscopy (XPS). Our N-doped carbons are highly suitable for electrochemical
      energy storage as supercapacitor electrodes, showing high specific capacitances
      in aqueous 1 m Li2 SO4 electrolyte (177 F g-1 ), organic 1 m tetraethylammonium
      tetrafluoroborate in acetonitrile (147 F g-1 ), and an ionic liquid (1-ethyl-3
      methylimidazolium tetrafluoroborate; 192 F g-1 ). This new mechanochemical
      pathway synergistically combines attractive energy-storage ratings with a
      scalable, time-efficient, cost-effective, and environmentally favorable
      synthesis.

PMID- 28436605
TI  - DiGeorge-like syndrome in a child with a 3p12.3 deletion involving MIR4273 gene
      born to a mother with gestational diabetes mellitus.
AB  - Chromosome 22q11.2 deletion is the most common chromosomal alteration associated
      with DiGeorge syndrome (DGS), even though this is not the only underlying cause
      of DGS. In rare patients, mutations in a single gene, TBX1, have been described
      resulting in a DGS phenotype. Recently, it has been reported that at least part
      of the TBX1 mutant phenotype is due to excessive bone morphogenetic proteins
      (BMP) signaling. Evidence suggests that miRNA may modulate the expression of
      critical T-box transcriptional regulators during midface development and Bmp
      signaling. We report on a 7-year-old Caucasian male born to a mother affected
      with gestational diabetes (GDM) who had a 371Kb-interstitial deletion of 3p12.3
      identified by array CGH, involving the ZNF717, MIR1243, and 4273 genes. The child
      presented with a DiGeorge anomaly (DGA) associated with unilateral renal agenesis
      and language delay. The immunological evaluation revealed a severe reduction and
      impairment of T lymphocytes. FISH analysis and TBX1 sequencing were negative.
      Among the miRNA-4273 predicted target genes, we found BMP3, which is involved in
      several steps of embryogenesis including kidney and lung organogenesis and in
      insulin gene expression. Since, DGA is not commonly found in newborns of diabetic
      mothers, we hypothesize that the pathogenesis of DGA associated with GDM is
      multifactorial, involving both genetic and/or epigenetic cofactors.

PMID- 28436606
TI  - Early and late adverse effects of radioiodine for pediatric differentiated
      thyroid cancer.
AB  - BACKGROUND: Radioiodine-131 (I131) therapy for differentiated thyroid cancer
      (DTC) is generally a safe and effective treatment, but it has some potential side
      effects, which have been well described in adults but less analyzed in children.
      Our aim was to describe early and late adverse events of radioactive I131 in
      pediatric patients. METHODS: All consecutive patients <=18 years treated for DTC
      in the period 1980-2015 were retrospectively analyzed for early and late side
      effects of radioiodine. Early side effects include nausea/emesis, radiation
      thyroiditis, sialadenitis, dry mouth, and transient bone marrow (BM) suppression.
      Late complications include permanent salivary gland dysfunction, permanent BM
      suppression, pulmonary fibrosis, second cancers, and fertility problems. RESULTS:
      One hundred five pediatric patients were treated with I131 for DTC in our
      department for a total amount of 302 radioiodine treatments. In total, 127 early
      complications were recorded: 44 episodes of nausea/emesis; 30 sialoadenitis, 24
      thyroiditis, 18 dry mouth, and 11 transient BM suppression. Early side effects
      were correlated with the amount of radioactivity administered in any treatment.
      Twelve children developed >=1 late complication for a total of 20 complications:
      two permanent salivary gland dysfunction, four permanent BM suppression, five
      pulmonary fibrosis, four second malignancies, and five fertility alterations.
      Late events, except fertility alterations, were correlated with the number of
      therapies and cumulative activities of I131. CONCLUSIONS: In conclusion, early
      side effects of I131 are associated with the amount of administrated activities
      of each treatment, while the late effects are correlated with the number of
      treatments and cumulative activities of radioiodine, except for fertility
      problems.

PMID- 28436607
TI  - Visual complaints in intracranial germinomas.
AB  - OBJECTIVE: Patients with brain tumors often report having visual complaints. This
      may be due to increased intracranial pressure, compression/invasion of the optic
      pathway or diplopia. We assessed the incidence and the etiology of visual
      symptoms in patients with intracranial germinoma tumors (ICGTs). METHODS AND
      MATERIALS: We performed a blinded retrospective review of the clinical charts and
      the initial magnetic resonance imaging (MRI) of 28 patients with ICGT. Thirteen
      tumors were pineal, five suprasellar, seven bifocal, and further three involved
      either the optic nerve, the corpus callosum, or the brainstem. RESULTS: Twelve
      patients reported visual disturbances, seven of whom mainly experienced a
      decrease in vision. Two of those were initially managed as "retrobulbar neuritis"
      when endocrinologic symptoms prompted assessment by MRI. Involvement of the optic
      pathway was underestimated, and both relapsed. Field deficits were definitive
      sequelae, whereas visual acuity was sometimes regressive in the absence of optic
      atrophy. CONCLUSIONS: Compression or invasion of the optic pathway by germinomas
      is not a rare occurrence, and this possibility should not be overlooked when
      thickening or contrast enhancement is detected. Radiotherapy fields should be
      extended accordingly.

PMID- 28436608
TI  - A Fukui function-guided genetic algorithm. Assessment on structural prediction of
      Sin (n = 12-20) clusters.
AB  - Theoretical studies are essential for the structural characterization of
      clusters, when it comes to rationalize their unique size-dependent properties and
      composition. However, the rapid growth of local minima on the potential energy
      surface (PES), with respect to cluster size, makes the candidate identification a
      challenging undertaking. In this article, we introduce a hybrid strategy to
      explore the PES of clusters. This proposal involves the use of a biased initial
      population of a genetic algorithm procedure. Each individual in this population
      is built by assembling small fragments, according to the best matching of the
      Fukui function. The performance of a genetic algorithm procedure. The performance
      of the method is assessed on the PES exploration of medium-sized Sin clusters (n
      = 12-20). The most relevant results are: (a) the method converges at almost half
      of the time used by the canonical version of the GA and, (b) in all the studied
      cases, with the exception of Si13 and Si16 , the method allowed to identify the
      global minimum (GM) and other important low-lying structures. Additionally, the
      apparent deficiency of the proposal to identify the GM was corrected when a Si
      atom, or other low-lying isomers, were considered to build the clusters. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28436609
TI  - A Semi-automated Approach to Create Purposeful Mechanistic Datasets from
      Heterogeneous Data: Data Mining Towards the in silico Predictions for Oestrogen
      Receptor Modulation and Teratogenicity.
AB  - The need to find an alternative to costly animal studies for developmental and
      reproductive toxicity testing has shifted the focus considerably to the
      assessment of in vitro developmental toxicology models and the exploitation of
      pharmacological data for relevant molecular initiating events. We hereby
      demonstrate how automation can be applied successfully to handle heterogeneous
      oestrogen receptor data from ChEMBL. Applying expert-derived thresholds to
      specific bioactivities allowed an activity call to be attributed to each data
      entry. Human intervention further improved this mechanistic dataset which was
      mined to develop structure-activity relationship alerts and an expert model
      covering 45 chemical classes for the prediction of oestrogen receptor modulation.
      The evaluation of the model using FDA EDKB and Tox21 data was quite encouraging.
      This model can also provide a teratogenicity prediction along with the additional
      information it provides relevant to the query compound, all of which will require
      careful assessment of potential risk by experts.

PMID- 28436610
TI  - Atomic Interface Engineering and Electric-Field Effect in Ultrathin Bi2 MoO6
      Nanosheets for Superior Lithium Ion Storage.
AB  - Ultrathin 2D materials can offer promising opportunities for exploring advanced
      energy storage systems, with satisfactory electrochemical performance.
      Engineering atomic interfaces by stacking 2D crystals holds huge potential for
      tuning material properties at the atomic level, owing to the strong layer-layer
      interactions, enabling unprecedented physical properties. In this work,
      atomically thin Bi2 MoO6 sheets are acquired that exhibit remarkable high-rate
      cycling performance in Li-ion batteries, which can be ascribed to the interlayer
      coupling effect, as well as the 2D configuration and intrinsic structural
      stability. The unbalanced charge distribution occurs within the crystal and
      induces built-in electric fields, significantly boosting lithium ion transfer
      dynamics, while the extra charge transport channels generated on the open
      surfaces further promote charge transport. The in situ synchrotron X-ray powder
      diffraction results confirm the material's excellent structural stability. This
      work provides some insights for designing high-performance electrode materials
      for energy storage by manipulating the interface interaction and electronic
      structure.

PMID- 28436611
TI  - Co-ingestion of willow bark tea and acetaminophen associated with fatal infantile
      fulminant liver failure.

PMID- 28436612
TI  - Effects of zero point vibration on the reaction dynamics of water dimer cations
      following ionization.
AB  - Reactions of water dimer cation (H2O)2+ following ionization have been
      investigated by means of a direct ab initio molecular dynamics method. In
      particular, the effects of zero point vibration and zero point energy (ZPE) on
      the reaction mechanism were considered in this work. Trajectories were run on two
      electronic potential energy surfaces (PESs) of (H2O)2+: ground state (2 A"-like
      state) and the first excited state (2 A'-like state). All trajectories on the
      ground-state PES lead to the proton-transferred product: H2 O+ (Wd)-H2 O(Wa) ->
      OH(Wd)-H3 O+ (Wa), where Wd and Wa refer to the proton donor and acceptor water
      molecules, respectively. Time of proton transfer (PT) varied widely from 15 to 40
      fs (average time of PT = 30.9 fs). The trajectories on the excited-state PES gave
      two products: an intermediate complex with a face-to-face structure (H2 O-OH2 )+
      and a PT product. However, the proton was transferred to the opposite direction,
      and the reverse PT was found on the excited-state PES: H2 O(Wd)-H2 O+ (Wa) -> H3
      O+ (Wd)-OH(Wa). This difference occurred because the ionizing water molecule in
      the dimer switched between the ground and excited states. The reaction mechanism
      of (H2O)2+ and the effects of ZPE are discussed on the basis of the results. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28436613
TI  - Paediatric acute care: Highlights from the Paediatric Acute Care-Advanced
      Paediatric Life Support Conference, Adelaide, 2016.
AB  - The Paediatric Acute Care Conference (PACC) is an annual conference organised by
      Advanced Paediatric Life Support Australia to advance paediatric acute care
      topics for clinicians in pre-hospital medicine, EDs, acute paediatrics, intensive
      care and anaesthesia. The PACC 2016 was held at Glenelg, Adelaide, Australia. We
      provide a summary of some of the presentations.

PMID- 28436614
TI  - Editorial Comment to Successful third renal transplantation in a child with an
      occluded inferior vena cava: A novel technique to use the venous interposition
      between the transplant renal vein and the infrahepatic inferior vena cava.

PMID- 28436615
TI  - Prenatal diagnosis of coronary artery fistula using 2D and 3D/4D ultrasound.

PMID- 28436617
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 19/2017.

PMID- 28436616
TI  - Reduced infectivity of waterborne viable but nonculturable Helicobacter pylori
      strain SS1 in mice.
AB  - BACKGROUND: Helicobacter pylori infection has been consistently associated with
      lack of access to clean water and proper sanitation, but no studies have
      demonstrated that the transmission of viable but nonculturable (VBNC) H. pylori
      can occur from drinking contaminated water. In this study, we used a laboratory
      mouse model to test whether waterborne VBNCH. pylori could cause gastric
      infection. MATERIALS AND METHODS: We performed five mouse experiments to assess
      the infectivity of VBNCH. pylori in various exposure scenarios. VBNC viability
      was examined using Live/Dead staining and Biolog phenotype metabolism arrays.
      High doses of VBNCH. pylori in water were chosen to test the "worst-case"
      scenario for different periods of time. One experiment also investigated the
      infectious capabilities of VBNC SS1 using gavage. Further, immunocompromised mice
      were exposed to examine infectivity among potentially vulnerable groups. After
      exposure, mice were euthanized and their stomachs were examined for H. pylori
      infection using culture and PCR methodology. RESULTS: VBNC cells were membrane
      intact and retained metabolic activity. Mice exposed to VBNCH. pylori via
      drinking water and gavage were not infected, despite the various exposure
      scenarios (immunocompromised, high doses) that might have permitted infection
      with VBNCH. pylori. The positive controls exposed to viable, culturable H. pylori
      did become infected. CONCLUSIONS: While other studies that have used viable,
      culturable SS1 via gavage or drinking water exposures to successfully infect
      mice, in our study, waterborne VBNC SS1 failed to colonize mice under all test
      conditions. Future studies could examine different H. pylori strains in similar
      exposure scenarios to compare the relative infectivity of the VBNC vs the viable,
      culturable state, which would help inform future risk assessments of H. pylori in
      water.

PMID- 28436619
TI  - Editorial Comment to Feasibility of single-session endoscopic combined intrarenal
      surgery for ipsilateral large renal stones and retrograde intrarenal surgery for
      contralateral renal stones: Initial experience.

PMID- 28436618
TI  - Natural history of aortic root dilation through young adulthood in a hypermobile
      Ehlers-Danlos syndrome cohort.
AB  - Hypermobile Ehlers-Danlos syndrome (hEDS) is a common inherited connective tissue
      disorder characterized by joint hypermobility. The natural history of aortic root
      dilation (AoD), a potential complication of EDS, has not been well characterized
      in this population. We describe the natural history of aortic root size in a
      large cohort of patients with hEDS. A cohort of 325 patients with HEDS was
      identified at Cincinnati Children's Hospital Medical Center (CCHMC), including
      163 patients from a previous study. Medical records were reviewed and each
      participant's height, weight, and aortic dimensions from up to four
      echocardiograms were documented. Aortic root z-scores were calculated using two
      established formulas based on age (Boston or Devereux). Overall prevalence of AoD
      and prevalence by age were calculated and longitudinal regression was performed.
      The prevalence of AoD with a z-score >= 2.0 was 14.2% (46/325) and with a z-score
      of >=3.0 was 5.5% (18/325). No significant increases in z-score were seen over
      time for patients with multiple echocardiograms. Participants under the age of 15
      years had an average decline of 0.1 standard deviations (SDs)/year. No
      significant change was found after 15 of age. Between the ages of 15 and 21
      years, Boston z-scores were 0.96 higher than Devereux z-scores. The nearly 1 z
      score unit difference between formulas indicates caution prior to diagnosing AoD
      in patients with hEDS. In light of the low prevalence and lack of progression of
      AoD, routine echocardiograms may not be warranted for pediatric patients with
      hEDS.

PMID- 28436620
TI  - Arginine-Rich Peptide-Based mRNA Nanocomplexes Efficiently Instigate Cytotoxic T
      Cell Immunity Dependent on the Amphipathic Organization of the Peptide.
AB  - To date, the mRNA delivery field has been heavily dominated by lipid-based
      systems. Reports on the use of nonlipid carriers for mRNA delivery in contrast
      are rare in the context of mRNA vaccination. This paper describes the potential
      of a cell-penetrating peptide containing the amphipathic RALA motif to deliver
      antigen-encoding mRNA to the immune system. RALA condenses mRNA into
      nanocomplexes that display acidic pH-dependent membrane disruptive properties.
      RALA mRNA nanocomplexes enable mRNA escape from endosomes and thereby allow
      expression of mRNA inside the dendritic cell cytosol. Strikingly, RALA mRNA
      nanocomplexes containing pseudouridine and 5-methylcytidine modified mRNA elicit
      potent cytolytic T cell responses against the antigenic mRNA cargo and show
      superior efficacy in doing so when compared to RALA mRNA nanocomplexes containing
      unmodified mRNA. RALA's unique sequence and structural organization are vital to
      act as mRNA vaccine vehicle, as arginine-rich peptide variants that lack the RALA
      motif show reduced mRNA complexation, impaired cellular uptake and lose the
      ability to transfect dendritic cells in vitro and to evoke T cell immunity in
      vivo.

PMID- 28436621
TI  - Risk factors for mortality before age 18 years in cystic fibrosis.
AB  - BACKGROUND: Understanding early-life risk factors for childhood death in cystic
      fibrosis (CF) is important for clinical care, including the identification of
      effective interventions. METHODS: Data from the Epidemiologic Study of Cystic
      Fibrosis (ESCF) collected 1994-2005 were linked with the Cystic Fibrosis
      Foundation Patient Registry (CFFPR) demographic and mortality data from 2013.
      Inclusion criteria were >=1 visit annually at age 3-5 years and >=1 FEV1
      measurement at age 6-8 years. Demographic data, nutritional parameters, pulmonary
      signs and symptoms, microbiology, and FEV1 were evaluated as risk factors for
      death before age 18 years. Multivariable Cox proportional hazards regression was
      used to model the simultaneous effects of risk factors associated with death
      before age 18 years. RESULTS: Among 5365 patients enrolled in ESCF who met
      inclusion criteria, 3880 (72%) were linked to the CFFPR. Among these, 191 (5.7%)
      died before age 18 years; median age at death was 13.4 +/- 3.1 years.
      Multivariable regression showed clubbing, crackles, female sex, unknown CFTR
      genotype, minority race or ethnicity, Medicaid insurance (a proxy of low
      socioeconomic status), Pseudomonas aeruginosa on 2 or more cultures, and weight
      for-age <50th percentile were significant risk factors for death regardless of
      inclusion of FEV1 at age 6-8 years in the model. CONCLUSION: We identified
      multiple risk factors for childhood death of patients with CF, all of which
      remained important after incorporating FEV1 at age 6-8 years. Among the factors
      identified were the presence of clubbing or crackles at age 3-5 years, signs
      which are not routinely collected in registries.

PMID- 28436622
TI  - Congenital intestinal fibrosarcoma with rapid recurrence requiring adjuvant
      chemotherapy.
AB  - A total of 16 cases of congenital fibrosarcoma have been reported from 1975 to
      March 2015. Five of the 16 had abnormal fusion between erythroblast
      transformation specific translocation variant 6 and neurotrophin recptor gene
      neurotrophic tyrosine kinase, receptor, type 3 (ETV6-NTRK3); in another five out
      of 16 this was absent, and six were not tested. All were managed by surgical
      resection but none involved metastasis. Herein we report the case of a newborn
      baby girl with congenital fibrosarcoma negative for ETV6-NTRK3 gene fusion, who
      presented with ileal perforation and positive resection margin. She had rapid
      recurrence with lymph node metastasis treated with postoperative chemotherapy.
      There was no further recurrence at >3 years of follow up.

PMID- 28436623
TI  - MTHFR methylation moderates the impact of smoking on DNA methylation at AHRR for
      African American young adults.
AB  - Smoking has been shown to have a large, reliable, and rapid effect on
      demethylation of AHRR, particularly at cg05575921, suggesting that methylation
      may be used as an index of cigarette consumption. Because the availability of
      methyl donors may also influence the degree of demethylation in response to
      smoking, factors that affect the activity of methylene tetrahydrofolate reductase
      (MTHFR), a key regulator of methyl group availability, may be of interest. In the
      current investigation, we examined the extent to which individual differences in
      methylation of MTHFR moderated the association between smoking and demethylation
      at cg05575921 as well as at other loci on AHRR associated with a main effect of
      smoking. Using a discovery sample (AIM, N = 293), and a confirmatory sample
      (SHAPE, N = 368) of young adult African Americans, degree of methylation of loci
      in the first exon of MTHFR was associated with amplification of the association
      between smoking and AHRR demethylation at cg05575921. However, genetic variation
      at a commonly studied MTHFR variant, C677T, did not influence cg05575921
      methylation. The significant interaction between MTHFR methylation and the
      smoking-induced response at cg05575921 suggests a role for individual differences
      in methyl cycle regulation in understanding the effects of cigarette consumption
      on genome wide DNA methylation.

PMID- 28436624
TI  - [Mechanisms of histamine ameliorating memory impairment induced by
      pentylenetetrazole-kindling epilepsy in rats].
AB  - Objective: To investigate the effects of neuronal histamine on spatial memory
      acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to
      explore its mechanisms. Methods: A subconvulsive dose of pentylenetetrazole (35
      mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical
      kindling until fully kindled. Morris water maze was used to measure the spatial
      memory acquisition of the rats one week after fully pentylenetetrazole-kindled,
      and the histamine contents in different brain areas were measured
      spectrofluorometrically. Different dosages of hitidine (the precursor of
      histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor
      antagonist) were intraperitoneally injected, and their effects on spatial memory
      acquisition of the rats were observed. Results: Compared with control group,
      escape latencies were significantly prolonged on Morris water maze training day 2
      and day 3 in pentylenetetrazole-kindling epilepsy rats (all P<0.05); and the
      histamine contents in hippocampus, thalamus and hypothalamus were decreased
      significantly (all P<0.05). Escape latencies were markedly shortened on day 3 by
      intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by
      intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole
      kindling epilepsy rats (all P<0.05). The protection of histidine was reversed by
      zolantidine (10 and 20 mg/kg), but not by pyrilamine. Conclusion: Neuronal
      histamine can improve the spatial memory acquisition impairment in rats with
      pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is
      possibly involved in the protective effects of histamine.

PMID- 28436625
TI  - [Effects of crocin on hippocampus rapid kindling epilepsy in mice].
AB  - Objective: To investigate the effect of crocin on the progression and generalized
      seizure of temporal lobe epilepsy in mice. Methods: Hippocampus rapid kindling
      model was established in C57BL/6J mice. The effects of crocin on seizure stage,
      afterdischarge duration (ADD), number of stimulation in each stage and final
      state, the incidence of generalized seizure (GS), average seizure stage and ADD
      were observed. Results: Crocin (20 mg/kg) significantly retarded behavioral
      seizure stages ( P<0.05) and shortened cumulative ADD ( P<0.01) during
      hippocampus rapid kindling acquisition in mice compared with vehicle group.
      Meanwhile, number of stimulations in stage 1-2 was significantly increased (
      P<0.05) and the incidence of fully kindled animals was significantly decreased (
      P<0.01). However, 10 or 50 mg/kg crocin showed no significant effect on the above
      indexes (all P>0.05). Crocin (100 or 200 mg/kg) significantly decreased the
      incidence of GS (all P<0.01) and reduced average seizure stages (all P<0.01) in
      fully-kindled mice compared with vehicle group; Fifty mg/kg crocin only reduced
      average seizure stages ( P<0.05). Conclusion: Low-dose crocin can retard the
      progression in hippocampus rapid kindling acquisition in mice, while high-dose
      crocin relieves the GS in fully-kindled mice, which suggests that crocin may be a
      potential anti-epileptic compound.

PMID- 28436626
TI  - [The role of central cholinergic system in epilepsy].
AB  - Epilepsy is a chronic neurological disorder, which is not only related to the
      imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons,
      but also related to abnormal central cholinergic regulation. This article
      summarizes the scientific background and experimental data about cholinergic
      dysfunction in epilepsy from both cellular and network levels, further discusses
      the exact role of cholinergic system in epilepsy. In the cellular level, several
      types of epilepsy are believed to be associated with aberrant metabotropic
      muscarinic receptors in several different brain areas, while the mutations of
      ionotropic nicotinic receptors have been reported to result in a specific type of
      epilepsy-autosomal dominant nocturnal frontal lobe epilepsy. In the network
      level, cholinergic projection neurons as well as their interaction with other
      neurons may regulate the development of epilepsy, especially the cholinergic
      circuit from basal forebrain to hippocampus, while cholinergic local interneurons
      have not been reported to be associated with epilepsy. With the development of
      optogenetics and other techniques, dissect and regulate cholinergic related
      epilepsy circuit has become a hotspot of epilepsy research.

PMID- 28436627
TI  - [Temporal lobe epilepsy and adult hippocampal neurogenesis].
AB  - Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which
      is often intractable. It can not only damage the normal structure and function of
      hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well
      documented from researches on the animal models of TLE that after a latent period
      of several days, prolonged seizure activity leads to a dramatic increase in
      mitotic activity in the hippocampal DG. However, cell proliferation returns to
      baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there
      are two major abnormalities of DG neurogenesis, including the formation of hilar
      basal dendrites and the ectopic migration of newborn granule cells into the
      polymorphic cell layer, which may affect epileptogenesis and seizure onset.
      However, the specific contribution of these abnormalities to seizures is still
      unknown. In other words, whether they are anti-epileptic or pro-epileptic is
      still under heated discussion. This article systematically reviews current
      knowledge on neurogenesis and epilepsy based on the results of studies in recent
      years and discusses the possible roles of neurogenesis in epileptogenesis and
      pathologic mechanisms, so as to provide information for the potential application
      of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.

PMID- 28436628
TI  - [Monitoring time of interictal epileptiform discharges by long-term video EEG in
      patients with epilepsy].
AB  - Objective: To optimize the monitoring time of interictal epileptiform discharges
      (IED) in patients with epilepsy by long-term video electroencephalogram (VEEG).
      Methods: The cumulative percentages of IED detected by VEEG in 346 epilepsy
      patients (349 times) with different purposes, different waking sleep states and
      different MRI findings were retrospectively analyzed. According to the purposes,
      there were 164 patients (165 times) for clarifying diagnosis, 124 patients (124
      times) for preoperative evaluation and 58 patients (60 times) for adjustment of
      medications. According to MRI results, there were responsible lesions in 98
      patients (98 times) and no responsible lesions in 173 patients (174 times).
      Results: Among 346 patients (349 times), IED was detected within 24 h in 231
      patients (times). The percentage of detection in patients with purpose of
      preoperative evaluation was higher than those with purpose of diagnosis and
      medication adjustment. The detection of LED was gradually increased in first 8 h
      with 59.0%, then stably in 24 h. 46.8% IED was recorded during sleep time,
      particularly in the second stage of sleep. The cumulative percentage of IED in
      patients with abnormal MRI findings was higher in all periods. It reached 83.7%
      within 8 h, and then tended to be stable. Conclusion: The study shows that LED
      should be monitored by VEEG at least 8 hours and should include the second stage
      of sleep in patients with epilepsy. Patients with refractory epilepsy and with
      abnormal lesions on MRI should record IED more frequently.

PMID- 28436629
TI  - [Hypoxia-inducible factor-1alpha and CD133 predicts pathological complete
      response and survival for locally advanced rectal cancer patients after
      neoadjuvant chemoradiotherapy].
AB  - Objective: To investigate the expression of hypoxia-inducible factor 1alpha (HIF
      1alpha) and CD133 in predicting pathologic remission and survival of patients
      with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy.
      Methods: One hundred and fourteen patients with locally advanced rectal cancer
      undergoing neoadjuvant chemoradiotherapy from January 2010 to December 2015 in
      Jinhua Municipal Central Hospital were enrolled in the study. RT-PCR and
      immunohistochemistry methods were used to detect the mRNA and protein expression
      of HIF-1alpha and CD133 before and after chemoradiotherapy. Spearman rank
      correlation was used to analyze the correlation between HIF-1alpha and CD133 mRNA
      expression. Univariate and logistic multivariate analyses were used to determine
      the factors related to pathological complete response (pCR). Logistic regression
      analysis and Cox's proportional hazard model were used to determine factors
      related to overall survival and recurrence-free survival. Results: The expression
      of HIF-1alpha and CD133 mRNA was correlated with pT, ypTNM, pCR, recurrence and
      metastasis of rectal cancer, while not correlated with sex, age and BMI of
      patients. HIF-1alpha mRNA expression was positively correlated with CD133 mRNA
      expression ( alpha=0.579, P=0.000). Immunohistochemistry analysis showed that
      residual cancer cells strongly expressing HIF-1alpha also expressed CD133
      strongly. Univariate analysis showed that HIF-1alpha mRNA and CD133 mRNA were
      significantly correlated with pCR ( P=0.001, P=0.022, respectively). Multivariate
      analysis showed that HIF-1alpha and CD133 mRNA expression were independent
      prognostic factors of pCR ( P=0.012, P=0.047, respectively). Cox regression
      analysis showed that the expression of HIF-1alpha mRNA and CD133 mRNA were
      independent predictors of recurrence-free survival and overall survival (
      P=0.025, P=0.033, respectively). Conclusion: The study indicates that HIF-1alpha
      and CD133 can predict pathological complete remission and survival of patients
      with locally advanced rectal cancer.

PMID- 28436630
TI  - [Clinical investigation on transarterial chemoembolization with indigenous drug
      eluting beads in treatment of unresectable hepatocellular carcinoma].
AB  - Objective: To evaluate the efficacy and safety of drug-eluding beads
      transarterial chemoembolization (DEB-TACE) in treatment of unrecectable
      hepatocellular carcinoma (HCC). Methods: The clinical data of 42 consecutive HCC
      patients undergoing TACE were retrospectively analyzed, including 20 cases
      received conventional TACE (cTACE group) and 22 cases received TACE with
      epirubicine-loaded microspheres (CalliSpheres (r)) (DEB-TACE group). MRI scans
      were performed 1 week before and 1, 3 and 6 months after initial therapy. The
      response to treatment, disease recurrence, complications and adverse effects were
      documented and compared between two groups. Results: There were no significant
      differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and
      disease control rate (CR+PR+SD), disease recurrence, complications and adverse
      effects of interventional therapy between cTACE group and DEB-TACE group.
      Additionally, there were no significant differences about locoregional biliary
      injuries, intrahepatic biloma, and newly detected intra- or extrahepatic HCC on
      MRI between cTACE group and DEB-TACE group. Conclusion: There were no
      statistically significant differences between cTACE group and DEB-TACE group with
      regard to the short-term response, disease recurrence, complications and side
      effects. Hepatic-locoregional complications may be more frequent in DEB-TACE
      group than those in cTACE group.

PMID- 28436631
TI  - [Video head impulse test for evaluation of vestibular function in patients with
      vestibular neuritis and benign paroxysmal positional vertigo].
AB  - Objective: To assess the clinical application of video head impulse test (vHIT)
      for vestibular function in vestibular neuritis (VN) and benign paroxysmal
      positional vertigo (BPPV) patients. Methods: Thirty-three patients with VN and 43
      patients with BPPV were enrolled from Sir Run Run Shaw Hospital and Ningbo Second
      Hospital from March 15 to September 10, 2015; and 50 healthy controls were also
      enrolled in the study. vHIT was used to quantitatively test the vestibulo-ocular
      reflex (VOR) gains of a pair of horizontal semicircular canals. VOR gains two
      pairs of vertical semicircular canals, and the corresponding asymmetrical value
      of three VOR gains. The saccades information was also recorded. Results: Compared
      with the healthy control group and BPPV patients, the affected horizontal and
      vertical VOR gains were declined and the corresponding asymmetries were increased
      in VN patients (all P<0.01). BPPV group also showed higher vertical VOR gain
      asymmetries compared with the healthy control group (all P<0.01), but no
      significant difference was observed in VOR gains and horizontal VOR gain
      asymmetry (all P>0.05). The sensibility of vHIT in diagnosis of VN was 87.9%.
      Among 33 VN patients, 22 were diagnosed with superior vestibular nerve
      dysfunction, 7 were found with inferior vestibular nerve dysfunction and 3 were
      with both dysfunction; and 1 case was not distinguished. Conclusion: Video head
      impulse test can quantitatively evaluate the vestibular dysfunction of VN and can
      help early diagnosis of VN, which may be widely used in clinic.

PMID- 28436632
TI  - [Localization of gestational age reference table and its application in prenatal
      screening].
AB  - Objective: To establish a fetal biparietal diameter (BPD)-gestational age formula
      based on the data of pregnant women from Xiaoshan District of Hangzhou, and to
      evaluate its application in prenatal screening. Methods: Data of 3500 pregnant
      women with gestational age between 15 weeks and 19 weeks+6 receiving prenatal
      screening in Xiaoshan Hospital during May 2014 and May 2015 were collected. BPDs
      were used to establish a localized BPD-gestational age formula. The localized
      formula was used to evaluate the prenatal screening risks in 1759 pregnant women
      with irregular menstrual cycles or uncertain last menstrual period (LMP) in
      Xiaoshan District, and the results were compared with those calculated using
      formula in LifeCycle 4.0. Results: With localized formula, the total positive
      rate of Down syndrome, trisomy 18 syndrome and deformity of neural tube was
      decreased from 6.96% to 5.85% ( P<0.05), in which the positive rate of Down
      syndrome decreased ( P<0.05), that of deformity of neural tube increased (
      P<0.05), and that of trisomy 18 syndrome remained the same ( P>0.05). The median
      MoMs of free-hCG beta and alpha-fetoprotein calculated using localized formula
      were significantly different from those calculated using the formula in LifeCycle
      4.0 (all P<0.05), and the former ones were more closer to 1. For women of fetus
      diagnosed with the above diseases, the positive rate calculated using localized
      formula was almost the same as that calculated using the formula in LifeCycle
      4.0. Conclusion: BPD-gestational age formula should be localized based on the
      statistical analysis of the local population, which will help to reduce the false
      positive rate, and make the results more accurate and reliable in prenatal
      screening.

PMID- 28436633
TI  - [LC/MS guided approach to discovering nephroprotective substances from Huangkui
      capsule].
AB  - Objective: To discover the nephroprotective substances from Huangkui capsule.
      Methods: The components of Huangkui capsule were isolated by preparative liquid
      chromatography, and the active components were screened by LC/MS and identified.
      The adriamycine-injured HK-2 cells were treated with various active components
      with different concentrations, and the malonaldehyde (MDA) content, adenosine
      triphosphate (ATP) level and mitochondrial oxygen consumption rate were measured
      to verify the protective activity of the compounds. Results: Four active
      components in Huangkui capsule were identified to exert nephroprotective effects.
      Fifteen flavanoids from these four components were tentatively identified by
      LC/MS, and hyperin, myricetin, quercetin, rutin and isoquercetin were confirmed.
      Hyperin, myricetin quercetin and rutin showed dose-dependent protective effects
      on injured HK-2 cells. Espacially, hyperin significantly reduced MDA content,
      quercetin and rutin significantly increased ATP level, and myricetin
      significantly increased mitochondrial oxygen consumption rate. Conclusion:
      Hyperin, myricetin, querctein and rutin might be the potential nephroprotective
      compounds in Huangkui capsule, their effects may be related to the inhibition of
      lipid peroxidation and the alleviation of mitochondrial damage.

PMID- 28436634
TI  - [Antiendotoxin effect of Jinhuaqingre capsules].
AB  - Objective: To investigate the anti-pyretic and anti-endotoxin effect of Chinese
      herb medicine Jinhuaqingre capsules. Methods: Thirty healthy male New Zealand
      rabbits with lipopolysaccharide-induced fever were divided into 5 groups (6
      rabbits in each): animals in model group were given normal saline by gavage,
      animals in positive control group were given aspirin (0.2 g/kg), and animals in
      Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0 or 1.5 g/kg,
      respectively. The changes in body temperature of rabbits were observed. Fifty
      healthy Kunming mice were divided into 5 groups (10 mice in each): mice in model
      group were given normal saline by gavage, mice in positive control group were
      given aspirin (0.2 g/kg), and those in Jinhuaqingre groups were given
      Jinhuaqingre capsules 6.0, 3.0, 1.5 g/kg, respectively. Matrix coloration method
      was used to detect the degradation rate of endotoxin in mice. Results: The body
      temperature in rabbits of high and medium dose Jinhuaqingre capsule groups
      declined significantly 60 min after drug administration, and the temperature of
      high-dose group returned to the baseline after 300 min; while the body
      temperature of low-dose group started to decline at 180 min after drug
      administration. The endotoxin degradation rates in mice of high, medium and low
      dose groups was (56.73+/-3.12)%, (47.23+/-1.77)% and (21.08+/-2.30)% at 30 min
      after drug administration; those were (82.76+/-1.00)%, (64.75+/-1.77)% and
      (38.21+/-1.57)% at 60 min after drug administration, respectively. Conclusion:
      Chinese herb medicine Jinhuanigre capsules have anti-pyretic and anti-endotoxin
      effects, which may provide a new option for the treatment of heat-toxin syndrome.

PMID- 28436635
TI  - [Application progress on near infrared spectroscopy in quality control and
      process monitoring of traditional Chinese medicine].
AB  - The industry of traditional Chinese medicine (TCM) encounters problems like
      quality fluctuation of raw materials and unstandardized production process. Near
      infrared (NIR) spectroscopy technology is widely used in quality control of TCM
      because of its abundant information, fast and nondestructive characters. The main
      applications include quantitative analysis of Chinese medicinal materials,
      intermediates and Chinese patent medicines; the authenticity of TCM, species,
      origins and manufacturers; monitoring and control of the extraction, alcohol
      precipitation, column chromatography and blending process. This article reviews
      the progress on the application of NIR spectroscopy technology in TCM field. In
      view of the problems existing in the application, the article proposes that the
      standardization of NIR analysis method should be developed according to specific
      characteristics of TCM, which will promote the application of NIR technology in
      the TCM industry.

PMID- 28436636
TI  - [Iodine 131 joint radio frequency ablation treatment for child with
      hyperthyroidism goiter: one case report].
AB  - A 12-year-old girl presented with a history of cervical mass, and one week of
      throat discomfort and dyspnea. Five years ago, the patient was diagnosed as
      Hashimoto's thyroiditis and hyperthyroidism; she received antithyroid drug
      treatment, but the result was not satisfactory. B-ultrasonic showed that the size
      of thyroid gland was 8.1 cm*3.2 cm in the left and 8.2 cm*4.8 cm in the right.
      After iodine 131 combined with radiofrequency ablation (RFA) treatment, throat
      discomfort and recumbent breathing difficulties disappeared, and B-ultrasonic
      showed that the size of thyroid reduced to 2.3 cm*1.7 cm (left) and 2.8 cm*2.0 cm
      (right). No recurrence was observed during the two and a half years of follow-up.

PMID- 28436637
TI  - [Research progress on mechanism of Nix-mediated mitophagy].
AB  - Autophagy is fundamental to maintain cellular homeostasis. As one kind of the
      most well-studied selective autophagy, autophagy of mitochondria (mitophagy)is
      crucial for the clearance of damaged mitochondria. Mitophagy dysfunction has been
      proved to be closely associated with many human diseases. Nix is a key protein
      for mitophagy during the maturation of reticulocytes. However, the detailed
      molecular mechanisms underlying Nix-mediated mitophagy are not fully understood.
      This article summarizes three possible working models of Nix in mitophagy
      induction. Firstly, Nix can interplay with Parkin, another important protein for
      mitophagy, to initiate mitophagy. Secondly, Nix can serve as a receptor for
      autophagy machinery by interacting with Atg8 family through its LIR motif.
      Finally, as a BH3-only protein, Nix can compete with Beclin-1 to bind other
      members of Bcl-2 family resulting in increased free Beclin-1 in cytosol, which
      further promotes autophagy flux.

PMID- 28436638
TI  - [Research progress on the animal models and treatment strategies of diabetic foot
      ulcer].
AB  - The suitable experimental animal model is important in research of pathogenesis
      and therapeutic strategies of diabetic foot ulcer, and the murine model is the
      most commonly used one at present. It can be divided into two types: the animal
      model simulating pathological conditions and the model simulating clinical
      symptoms. This article reviews the current research progress on the mechanisms of
      diabetic ulcer pathogenesis, and relevant treatment strategies, including the
      inhibition of matrix metalloproteinases (MMPs) expression, promotion of
      angiogenesis and anti-inflammatory therapy.

PMID- 28436639
TI  - [Focus on the 14th International Symposium on Dendritic Cells].

PMID- 28436640
TI  - Intravitreal Aflibercept for Patients With Diabetic Macular Edema Refractory to
      Bevacizumab or Ranibizumab: Analysis of Response to Aflibercept.
AB  - PURPOSE: To investigate the short-term efficacy and safety of intravitreal
      aflibercept in a case series of patients with diabetic macular edema (DME)
      refractory to ranibizumab or bevacizumab. DESIGN: A retrospective chart review.
      METHODS: From September 2013 to March 2016, we identified patients with DME who
      developed resistance to bevacizumab or ranibizumab. Three monthly intravitreal
      aflibercept injections were administered in refractory cases. Nonresponse to
      aflibercept was defined as a paradoxical increase in central foveal thickness
      (CFT) and gain in best-corrected visual acuity (BCVA) of less than 1 line at 1
      month after treatment compared with before aflibercept administration. RESULTS:
      Out of a total of 72 eyes in 72 refractory patients, 42 eyes (58.3%) responded to
      aflibercept injections. The BCVA and CFT were 0.65 +/- 0.32 logMAR and 438.5 +/-
      80.1 MUm, respectively, before aflibercept treatment and significantly improved
      to 0.31 +/- 0.17 logMAR (P = 0.0008) and 297.9 +/- 19.1 MUm (P = 0.0004),
      respectively, 1 month after 3 aflibercept injections in responders. No
      differences in baseline characteristics, including age, sex, glycosylated
      hemoglobin, serum creatinine, total cholesterol, lens status, grades of diabetic
      retinopathy, and CFT/BCVA before aflibercept management (P > 0.05), were observed
      between responders and nonresponders. There were 17 vitrectomized eyes in 30
      nonresponders (56.7%), a significantly higher rate than among the 42 responders
      (0%; P = 0.00001). CONCLUSIONS: Three monthly intravitreal aflibercept injections
      had benefit in nearly two thirds of cases with DME resistant to bevacizumab or
      ranibizumab over short-term follow-up. Vitrectomized eyes responded poorly to
      aflibercept treatment.

PMID- 28436641
TI  - The medicalization of prevention: health promotion is more than a pill a day

PMID- 28436642
TI  - The Validity of Race and Hispanic-origin Reporting on Death Certificates in the
      United States: An Update.
AB  - ObjectivesThis report presents the findings of an updated study of the validity
      of race and Hispanic-origin reporting on death certificates in the United States,
      and its impact on race- and Hispanic origin-specific death rates.MethodsThe
      latest version of the National Longitudinal Mortality Study (NLMS) was used to
      evaluate the classification of race and Hispanic origin on death certificates for
      deaths occurring in 1999-2011 to decedents in NLMS. To evaluate change over time,
      these results were compared with those of a study based on an earlier version of
      NLMS that evaluated the quality of race and ethnicity classification on death
      certificates for 1979-1989 and 1990-1998. NLMS consists of a series of annual
      Current Population Survey files (1973 and 1978-2011) and a sample of the 1980
      decennial census linked to death certificates for 1979-2011. Pooled 2009-2011
      vital statistics mortality data and 2010 decennial census population data were
      used to estimate and compare observed and corrected race- and Hispanic origin
      specific death rates.ResultsRace and ethnicity reporting on death certificates
      continued to be highly accurate for both white and black populations during the
      1999-2011 period. Misclassification remained high at 40% for the American Indian
      or Alaska Native (AIAN) population. It improved, from 5% to 3%, for the Hispanic
      population, and from 7% to 3% for the Asian or Pacific Islander (API) population.
      Decedent characteristics such as place of residence and nativity affected the
      quality of reporting on the death certificate. Effects of misclassification on
      death rates were large for the AIAN population but not significant for the
      Hispanic or API populations.

PMID- 28436643
TI  - Ultrathin In2O3 Nanosheets with Uniform Mesopores for Highly Sensitive Nitric
      Oxide Detection.
AB  - Nitric oxide (NOx, including NO and NO2) is one of the most dangerous
      environmental toxins and pollutants, which mainly originates from vehicle exhaust
      and industrial emission. The development of sensitive NOx gas sensors is quite
      urgent for human health and the environment. Up to now, it still remains a great
      challenge to develop a NOx gas sensor, which can satisfy multiple application
      demands for sensing performance (such as high response, low detection
      temperature, and limit). In this work, ultrathin In2O3 nanosheets with uniform
      mesopores were successfully synthesized through a facile two-step synthetic
      method. This is a success due to not only the formation of two-dimensional (2D)
      nanosheets with an ultrathin thickness of 3.7 nm based on a nonlayered compound
      but also the template-free construction of uniform mesopores in ultrathin
      nanosheets. The sensors based on the as-obtained mesoporous In2O3 ultrathin
      nanosheets exhibit an ultrahigh response (Rg/Ra = 213) and a short response time
      (ca. 4 s) toward 10 ppm NOx, and a quite low detection limit (10 ppb NOx) under a
      relatively low operating temperature (120  degrees C), which well satisfies
      multiple application demands. The excellent sensing performance should be mainly
      attributed to the unique structural advantages of mesopores and 2D ultrathin
      nanosheets.

PMID- 28436644
TI  - Ultrathin TiO2(B) Nanosheets as the Inductive Agent for Transfrering H2O2 into
      Superoxide Radicals.
AB  - A reflux method to synthesize ultrathin polycrystalline TiO2(B) nanosheets (NSs)
      which are assembled by single crystals, and further stacked into nanoflower
      structures, is described. On the basis of the theoretical calculations and
      experiments, H2O2 can easily substitute the ethylene glycol adsorbed on the
      surface of TiO2(B) NSs, forming H2O2-NS due to the lower adsorption energy and
      the unique structural features of ultrathin TiO2(B) nanosheets. TiO2(B) NSs and
      the H2O2 system can be accelerated to generate superoxide radicals under heat or
      light and thus exhibit a great degradation property on dye molecules; the total
      organic carbon (TOC) removal rate was 6 times higher than that for H2O2 alone.
      Meanwhile, TiO2(B) NSs and the H2O2 system have a good application on the
      selective oxidation due to the reactive species of superoxide radicals avoiding
      overoxidization of benzyl alcohol. The conversion of benzyl alcohol oxidized to
      benzaldehyde in water solution under low temperature and atmospheric pressure was
      51.13%, while the selectivity was close to 100%. We believe that the present
      findings will provide valuable methods for highly efficient generation of
      superoxide radicals and broaden their applications in catalysis.

PMID- 28436645
TI  - Rethinking Wastewater Treatment Plant Effluent Standards: Nutrient Reduction or
      Nutrient Control?

PMID- 28436646
TI  - Filaments with Affinity Binding and Wet Strength Can Be Achieved by Spinning
      Bifunctional Cellulose Nanofibrils.
AB  - We demonstrate benzophenone (BP) conjugation via amine-reactive esters onto
      oxidized cellulosic fibers that were used as precursors, after microfluidization,
      of photoactive cellulose nanofibrils (CNF). From these fibrils, cellulose I
      filaments were synthesized by hydrogel spinning in an antisolvent followed by
      fast biradical UV cross-linking. As a result, the wet BP-CNF filaments retained
      extensively the original dry strength (a remarkable ~80% retention). Thus, the
      principal limitation of these emerging materials was overcome (the wet tensile
      strength is typically <0.5% of the value measured in dry conditions).
      Subsequently, antihuman hemoglobin (anti-Hb) antibodies were conjugated onto
      residual surface carboxyl groups, making the filaments bifunctional for their
      active groups and properties (wet strength and bioactivity). Optical (surface
      plasmon resonance) and electroacoustic (quartz crystal microgravimetry)
      measurements conducted with the bifunctional CNF indicated effective anti-Hb
      conjugation (2.4 mg m-2), endowing an excellent sensitivity toward Hb targets
      (1.7 +/- 0.12 mg m-2) and negligible nonspecific binding. Thus, the anti-Hb
      biointerface was deployed on filaments that captured Hb efficiently from aqueous
      matrices (confocal laser microscopy of FITC-labeled antibodies). Significantly,
      the anti-Hb biointerface was suitable for regeneration, while its sensitivity and
      selectivity in affinity binding can be tailored by application of blocking
      copolymers. The developed bifunctional filaments based on nanocellulose offer
      great promise in detection and affinity binding built upon 1D systems, which can
      be engineered into other structures for rational use of material and space.

PMID- 28436647
TI  - High-Performance Hydrogen Storage Nanoparticles Inside Hierarchical Porous Carbon
      Nanofibers with Stable Cycling.
AB  - An effective route based on space-confined chemical reaction to synthesize
      uniform Li2Mg(NH)2 nanoparticles is reported. The hierarchical pores inside the
      one-dimensional carbon nanofibers (CNFs), induced by the creation of well
      dispersed Li3N, serve as intelligent nanoreactors for the reaction of Li3N with
      Mg-containing precursors, resulting in the formation of uniformly discrete
      Li2Mg(NH)2 nanoparticles. The nanostructured Li2Mg(NH)2 particles inside the CNFs
      are capable of complete hydrogenation and dehydrogenation at a temperature as low
      as 105  degrees C with the suppression of ammonia release. Furthermore, by virtue
      of the nanosize effects and space-confinement by the porous carbon scaffold, no
      degradation was observed after 50 de/rehydrogenation cycles at a temperature as
      low as 130  degrees C for the as-prepared Li2Mg(NH)2 nanoparticles, indicating
      excellent reversibility. Moreover, the theoretical calculations demonstrate that
      the reduction in particle size could significantly enhance the H2 sorption of
      Li2Mg(NH)2 by decreasing the relative activation energy barrier, which agrees
      well with our experimental results. This method could represent an effective,
      general strategy for synthesizing nanoparticles of complex hydrides with stable
      reversibility and excellent hydrogen storage performance.

PMID- 28436648
TI  - Statistical Variable Selection: An Alternative Prioritization Strategy during the
      Nontarget Analysis of LC-HR-MS Data.
AB  - Liquid chromatography coupled to high resolution mass spectrometry (LC-HR-MS) has
      been one of the main analytical tools for the analysis of small polar organic
      pollutants in the environment. LC-HR-MS typically produces a large amount of data
      for a single chromatogram. The analyst is therefore required to perform
      prioritization prior to nontarget structural elucidation. In the present study,
      we have combined the F-ratio statistical variable selection and the apex
      detection algorithms in order to perform prioritization in data sets produced via
      LC-HR-MS. The approach was validated through the use of semisynthetic data, which
      was a combination of real environmental data and the artificially added signal of
      31 alkanes in that sample. We evaluated the performance of this method as a
      function of four false detection probabilities, namely: 0.01, 0.02, 0.05, and
      0.1%. We generated 100 different semisynthetic data sets for each F-ratio and
      evaluated that data set using this method. This design of experiment created a
      population of 30 000 true positives and 32 000 true negatives for each F-ratio,
      which was considered sufficiently large enough in order to fully validate this
      method for analysis of LC-HR-MS data. The effect of both the F-ratio and signal
      to-noise ratio (S/N) on the performance of the suggested approach were evaluated
      through normalized statistical tests. We also compared this method to the pixel
      by-pixel as well as peak list approaches. More than 92% of features present in
      the final feature list via the F-ratio method were also present in the
      conventional peak list generated by MZmine. However, this method was the only
      approach successful in the classification of samples, and thus prioritization,
      when compared to the other evaluated approaches. The application potential and
      limitations of the suggested method are discussed.

PMID- 28436649
TI  - Multi-Arm Junctions for Dynamic DNA Nanotechnology.
AB  - Nonenzymatic catalytic substrates have been engineered using toehold-mediated DNA
      strand displacement, and their programmable applications range from medical
      diagnosis to molecular computation. However, the complexity, stability,
      scalability, and sensitivity of those systems are plagued by network leakage. A
      novel way to suppress leakage is to increase its energy barrier through four-way
      branch migration. Presented here, we designed multi-arm junction substrates that
      simultaneously exploit four-way branch migration, with a high-energy barrier to
      minimize leakage, and three-way branch migration, with a low-energy barrier to
      maximize catalysis. Original feed forward, autocatalytic, and cross-catalytic
      systems have been designed with polynomial and exponential amplification that
      exhibit the modularity of linear substrates and the stability of hairpin
      substrates, creating a new phase space for synthetic biologist, biotechnologist,
      and DNA nanotechnologists to explore. A key insight is that high-performing
      circuits can be engineered in the absence of intensive purification and/or
      extensive rounds of design optimization. Without adopting established leakage
      suppression techniques, the ratio of the catalytic rate constant to the leakage
      rate constant is more than 2 orders of magnitude greater than state-of-the-art
      linear and hairpin substrates. Our results demonstrate that multi-arm junctions
      have great potential to become central building blocks in dynamic DNA
      nanotechnology.

PMID- 28436650
TI  - Coupling Two-Dimensional MoTe2 and InGaZnO Thin-Film Materials for Hybrid PN
      Junction and CMOS Inverters.
AB  - We report the fabrication of hybrid PN junction diode and complementary (CMOS)
      inverters, where 2D p-type MoTe2 and n-type thin film InGaZnO (IGZO) are coupled
      for each device process. IGZO thin film was initially patterned by conventional
      photolithography either for n-type material in a PN diode or for n-channel of top
      gate field-effect transistors (FET) in CMOS inverter. The hybrid PN junction
      diode shows a good ideality factor of 1.57 and quite a high ON/OFF rectification
      ratio of ~3 * 104. Under photons, our hybrid PN diode appeared somewhat stable
      only responding to high-energy photons of blue and ultraviolet. Our 2D nanosheet
      oxide film hybrid CMOS inverter exhibits voltage gains as high as ~40 at 5 V, low
      power consumption less than around a few nW at 1 V, and ~200 MUs switching
      dynamics.

PMID- 28436651
TI  - Synthesis of Dicarba-closo-dodecaborane-1-carboxamides.
AB  - Amide bond formation is one of the most important chemical reactions. In peptide
      and organic chemistry, the application of amide coupling reagents is a routine
      strategy, but surprisingly not in carborane chemistry. Thus, we now report a
      fast, safe, and robust protocol to couple amines to m- and p-dicarba-closo
      dodecaborane-1-carboxylic acids. The procedure comprises the activation of
      carboxylic acid with the coupling reagent (1-cyano-2-ethoxy-2
      oxoethylidenaminooxy)(dimethylamino)morpholinocarbenium hexafluorophosphate,
      extraction of the product using the hydrophobic nature of the cluster, and a
      straightforward chromatographic purification. The protocol allows access to a
      variety of carborane-organic hybrid molecules suitable for application in
      multiple areas.

PMID- 28436652
TI  - Observation of the Generation of ONOO- in Mitochondria under Various Stimuli with
      a Sensitive Fluorescence Probe.
AB  - Peroxynitrite (ONOO-), an important reactive oxygen species (ROS), may be
      generated in the mitochondria under various physiological and pathological
      conditions. In this work, we designed and synthesized a mitochondria-targetable
      fluorescence probe RPTPP by using rhodamine as the fluorophore, phenylhydrazine
      as the recognition moiety, and triphenyl-phosphonium cation as the mitochondria
      targeting moiety. Upon reaction of the probe with ONOO-, the oxidation of
      phenylhydrazine by ONOO- and the subsequent hydrolysis opens the nonfluorescent
      spirocyclic structure and, thus, triggers a fluorescence turn-on response, which
      provides a sensitive and selective method for the detection of ONOO-. The
      mitochondria-targeting property of RPTPP was confirmed by the colocalization
      experiments as well as the mitochondria uncoupling treatments. Moreover, the
      applications of the probe for imaging intracellular ONOO- were performed in
      living cells, which reveals that the ONOO- level in RAW264.7 cells undergoes an
      about 9-fold increase with the stimulation of LPS and IFN-gamma for 15 h.

PMID- 28436653
TI  - Na8MB21O36 (M = Rb and Cs): Noncentrosymmetric Borates with Unprecedented
      [B21O36]9- Fundamental Building Blocks.
AB  - Two noncentrosymmetric borates, Na8MB21O36 (M = Rb and Cs), have been
      synthesized, structurally analyzed, and characterized for the first time. Their
      fundamental building block (FBB) is determined as the unprecedented [B21O36]9-
      units, which is cotemplated by four-connected [BO4]5- and five-connected [B5O11]7
      clusters. To the best of our knowledge, the [B21O36]9- FBB has never been
      reported in borates. Besides, the structure comparisons among all the available
      anhydrous borates with high-polymeric FBBs were carried out to enlighten the
      investigation of B-rich borates.

PMID- 28436654
TI  - Crystal-Phase Transitions and Photocatalysis in Supramolecular Scaffolds.
AB  - The energy landscape of a supramolecular material can include different molecular
      packing configurations that differ in stability and function. We report here on a
      thermally driven crystalline order transition in the landscape of supramolecular
      nanostructures formed by charged chromophore amphiphiles in salt-containing
      aqueous solutions. An irreversible transition was observed from a metastable to a
      stable crystal phase within the nanostructures. In the stable crystalline phase,
      the molecules end up organized in a short scroll morphology at high ionic
      strengths and as long helical ribbons at lower salt content. This is interpreted
      as the result of the competition between electrostatic repulsive forces and
      attractive molecular interactions. Only the stable phase forms charge-transfer
      excitons upon exposure to visible light as indicated by absorbance and
      fluorescence features, second-order harmonic generation microscopy, and
      femtosecond transient absorbance spectroscopy. Interestingly, the supramolecular
      reconfiguration to the stable crystalline phase nanostructures enhances
      photosensitization of a proton reduction catalyst for hydrogen production.

PMID- 28436656
TI  - Cellulose Anionic Hydrogels Based on Cellulose Nanofibers As Natural Stimulants
      for Seed Germination and Seedling Growth.
AB  - Cellulose anionic hydrogels were successfully prepared by dissolving TEMPO
      oxidized cellulose nanofibers in NaOH/urea aqueous solution and being cross
      linked with epichlorohydrin. The hydrogels exhibited microporous structure and
      high hydrophilicity, which contribute to the excellent water absorption property.
      The growth indexes, including the germination rate, root length, shoot length,
      fresh weight, and dry weight of the seedlings, were investigated. The results
      showed that cellulose anionic hydrogels with suitable carboxylate contents as
      plant growth regulators could be beneficial for seed germination and growth.
      Moreover, they presented preferable antifungal activity during the breeding and
      growth of the sesame seed breeding. Thus, the cellulose anionic hydrogels with
      suitable carboxylate contents could be applied as soilless culture mediums for
      plant growth. This research provided a simple and effective method for the
      fabrication of cellulose anionic hydrogel and evaluated its application in
      agriculture.

PMID- 28436655
TI  - Investigating the Antibacterial Activity of Biphenylthiazoles against Methicillin
      and Vancomycin-Resistant Staphylococcus aureus (MRSA and VRSA).
AB  - Phenylthiazoles were reported previously as a new scaffold with antibacterial
      activity against an array of multidrug-resistant staphylococci. However, their
      promising antibacterial activity was hampered in large part by their short half
      life due to excessive hepatic clearance. Close inspection of the structure
      activity-relationships (SARs) of the phenylthiazoles revealed two important
      structural features necessary for antibacterial activity (a nitrogenous and a
      lipophilic component). Incorporating the nitrogenous part within a pyrimidine
      ring resulted in analogues with a prolonged half-life, while the biphenyl moiety
      revealed the most potent analogue 1b. In this study, advantageous moieties have
      been combined to generate a new hybrid scaffold of 5-pyrimidinylbiphenylthiazole
      with the objective of enhancing both anti-MRSA activity and drug-like properties.
      Among the 37 tested biphenylthiazoles, piperazinyl-containing derivatives 10, 30,
      and 36 were the most potent analogues with MIC values as low as 0.39 MUg/mL.
      Additionally, 36 exhibited significant improvement in stability to hepatic
      metabolism.

PMID- 28436657
TI  - Role of Humic Acid in the Stability of Ag Nanoparticles in Suboxic Conditions.
AB  - Stability and temporal changes in size distributions have been observed for
      citrate- (cit) and polyvinylpyrrolidone- (PVP) capped silver nanoparticles
      (AgNPs), in the presence or absence of sulfide and natural organic matter (NOM,
      as humic acid), while under suboxic conditions. There were substantial
      differences in the influence of the two capping agents, with PVP-AgNPs showing
      few or no significant changes in apparent stability or particle size distribution
      under the conditions examined, while the apparent size distributions of citrate
      capped AgNPs changed rapidly. Sulfide and humic acid each individually caused
      immediate increases in cit-AgNP size distributions, which were then relatively
      stable over 60-145 days. This may be due to sulfide bridging and cation bridging,
      respectively. However, in competition, it was the influence of the humic acid
      that dominated that of the sulfide. These observations have implications for
      environmental fate and toxicity of AgNP. The increased stability in the presence
      of even low concentrations of NOM may limit the rapidity of Ag dispersal but may
      also concentrate the dose received by organisms, which subsequently ingest the
      stabilized particles.

PMID- 28436658
TI  - Chemical Composition and Acetylcholinesterase Inhibitory Activity of Essential
      Oils from Piper Species.
AB  - The essential oils (EOs) derived from aromatic plants such as Piper species are
      considered to play a role in alleviating neuronal ailments that are associated
      with inhibition of acetylcholinesterase (AChE). The chemical compositions of 23
      EOs prepared from 16 Piper spp. were analyzed by both gas chromatography with a
      flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC
      MS). A total of 76 compounds were identified in the EOs from the leaves and stems
      of 19 samples, while 30 compounds were detected in the EOs from the fruits of
      four samples. Sesquiterpenes and phenylpropanoids were found to be rich in these
      EOs, of which asaricin, caryophyllene, caryophyllene oxide, isospathulenol, (+)
      spathulenol, and beta-bisabolene are the major constituents. The EOs from the
      leaves and stems of Piper austrosinense, P. puberulum, P. flaviflorum, P. betle,
      and P. hispidimervium showed strong AChE inhibitory activity with IC50 values in
      the range of 1.51 to 13.9 mg/mL. A thin-layer chromatography (TLC) bioautography
      assay was employed to identify active compound(s) in the most active EO from P.
      hispidimervium. The active compound was isolated and identified as asaricin,
      which gave an IC50 value of 0.44 +/- 0.02 mg/mL against AChE, comparable to
      galantamine with an IC50 0.15 +/- 0.01 mg/mL.

PMID- 28436659
TI  - Fluorescence and Scattering Light Cross Correlation Spectroscopy and Its
      Applications in Homogeneous Immunoassay.
AB  - In this work, we propose fluorescence and scattering light cross-correlation
      spectroscopy (FSCCS) based on laser confocal configuration using silver
      nanoparticle (SNPs) and Alexa Fluor 488 (Alexa) as probe pairs. FSCCS is a single
      molecule (particle) method, and its principle is similar to that of fluorescence
      cross-correlation spectroscopy (FCCS). We established the setup of FSCCS using
      single wavelength laser and developed an immunoassay model of FSCCS. The
      reliability and adaptability of FSCCS method were evaluated by homogeneous
      sandwich immunoassay mode. In the study, liver cancer biomarker alpha-fetoprotein
      (AFP) was used as an assay model, two different antibodies were labeled with SNPs
      and fluorophore Alexa Fluor 488, respectively. In the optimal conditions, the
      linear range of AFP covers 5 pM to 580 pM and the detection limit is 3.1 pM. This
      method was successfully applied for direct determination of AFP levels in human
      serum samples, and the obtained results were in good agreement with data obtained
      via ELISAs. The advantage of this method lies in its simplicity, attractive SNPs
      probes, high sensitivity and selectivity and high efficiency. We believe that
      FSCCS method exhibits promising potential applications in homogeneous bioassays
      and study on the molecular interaction and nanoparticle-molecule interaction.

PMID- 28436660
TI  - Efficient Charge Separation of Cold Charge-Transfer States in Organic Solar Cells
      Through Incoherent Hopping.
AB  - We demonstrate that efficient and nearly field-independent charge separation of
      electron-hole pairs in organic planar heterojunction solar cells can be described
      by an incoherent hopping mechanism. Using kinetic Monte Carlo simulations that
      include the effect of on-chain delocalization as well as entropic contributions,
      we simulate the dissociation of the charge-transfer state in polymer-fullerene
      bilayer solar cells. The model further explains experimental results of almost
      field independent charge separation in bilayers of molecular systems with
      fullerenes and provides important guidelines at the molecular level for
      maximizing the efficiencies of organic solar cells. Thus, utilizing coherent
      phenomena is not necessarily required for highly efficient charge separation in
      organic solar cells.

PMID- 28436662
TI  - Multiconfiguration Pair-Density Functional Theory Predicts Spin-State Ordering in
      Iron Complexes with the Same Accuracy as Complete Active Space Second-Order
      Perturbation Theory at a Significantly Reduced Computational Cost.
AB  - The spin-state orderings in nine Fe(II) and Fe(III) complexes with ligands of
      diverse ligand-field strength were investigated with multiconfiguration pair
      density functional theory (MC-PDFT). The performance of this method was compared
      to that of complete active space second-order perturbation theory (CASPT2) and
      Kohn-Sham density functional theory. We also investigated the dependence of
      CASPT2 and MC-PDFT results on the size of the active-space. MC-PDFT reproduces
      the CASPT2 spin-state ordering, the dependence on the ligand field strength, and
      the dependence on active space at a computational cost that is significantly
      reduced as compared to CASPT2.

PMID- 28436661
TI  - Performance of van der Waals Corrected Functionals for Guest Adsorption in the
      M2(dobdc) Metal-Organic Frameworks.
AB  - Small-molecule binding in metal-organic frameworks (MOFs) can be accurately
      studied both experimentally and computationally, provided the proper tools are
      employed. Herein, we compare and contrast properties associated with guest
      binding by means of density functional theory (DFT) calculations using nine
      different functionals for the M2(dobdc) (dobdc4- = 2,5-dioxido,1,4
      benzenedicarboxylate) series, where M = Mg, Mn, Fe, Co, Ni, Cu, and Zn.
      Additionally, we perform Quantum Monte Carlo (QMC) calculations for one system to
      determine if this method can be used to assess the performance of DFT. We also
      make comparisons with previously published experimental results for carbon
      dioxide and water and present new methane neutron powder diffraction (NPD) data
      for further comparison. All of the functionals are able to predict the
      experimental variation in the binding energy from one metal to the next; however,
      the interpretation of the performance of the functionals depends on which value
      is taken as the reference. On the one hand, if we compare against experimental
      values, we would conclude that the optB86b-vdW and optB88-vdW functionals
      systematically overestimate the binding strength, while the second generation of
      van der Waals (vdW) nonlocal functionals (vdw-DF2 and rev-vdW-DF2) correct for
      this providing a good description of binding energies. On the other hand, if the
      QMC calculation is taken as the reference then all of the nonlocal functionals
      yield results that fall just outside the error of the higher-level calculation.
      The empirically corrected vdW functionals are in reasonable agreement with
      experimental heat of adsorptions but under bind when compared with QMC, while
      Perdew-Burke-Ernzerhof fails by more than 20 kJ/mol regardless of which reference
      is employed. All of the functionals, with the exception of vdW-DF2, predict
      reasonable framework and guest binding geometries when compared with NPD
      measurements. The newest of the functionals considered, rev-vdW-DF2, should be
      used in place of vdW-DF2, as it yields improved bond distances with similar
      quality binding energies.

PMID- 28436663
TI  - Introducing Ionic-Current Detection for X-ray Absorption Spectroscopy in Liquid
      Cells.
AB  - Photons and electrons are two common relaxation products upon X-ray absorption,
      enabling fluorescence yield and electron yield detections for X-ray absorption
      spectroscopy (XAS). The ions that are created during the electron yield process
      are relaxation products too, which are exploited in this study to produce ion
      yield for XA detection. The ionic currents measured in a liquid cell filled with
      water or iron(III) nitrate aqueous solutions exhibit characteristic O K-edge and
      Fe L-edge absorption profiles as a function of excitation energy. Application of
      two electrodes installed in the cell is crucial for obtaining the XA spectra of
      the liquids behind membranes. Using a single electrode can only probe the species
      adsorbed on the membrane surface. The ionic-current detection, termed as total
      ion yield (TIY) in this study, also produces an undistorted Fe L-edge XA
      spectrum, indicating its promising role as a novel detection method for XAS
      studies in liquid cells.

PMID- 28436664
TI  - CPPred-RF: A Sequence-based Predictor for Identifying Cell-Penetrating Peptides
      and Their Uptake Efficiency.
AB  - Cell-penetrating peptides (CPPs), have been proven as important drug-delivery
      vehicles, demonstrating the potential as therapeutic candidates. The past decade
      has witnessed a rapid growth in CPP-based research. Recently, many computational
      efforts have been made to develop machine-learning-based methods for identifying
      CPPs. Although much progress has been made, existing methods still suffer low
      feature representation capability that limits further performance improvement. In
      this study, we propose a novel predictor called CPPred-RF, in which we integrate
      multiple sequence-based feature descriptors to sufficiently explore distinct
      information embedded in CPPs, employ a well-established feature selection
      technique to improve the feature representation, and, for the first time,
      construct a two-layer prediction framework based on the random forest algorithm.
      The jackknife results on benchmark data sets show that the proposed CPPred-RF is
      at least competitive with the state-of-the-art predictors. Moreover, we establish
      the first online Web server in terms of predicting CPPs and their uptake
      efficiency simultaneously. It is freely available at
      http://server.malab.cn/CPPred-RF .

PMID- 28436665
TI  - Intra- and Interskeletal Proteome Variations in Fresh and Buried Bones.
AB  - Proteomic methods are acquiring greater importance in archaeology and
      palaeontology due to the longevity of proteins in skeletal remains. There are
      also developing interests in forensic applications, offering the potential to
      shed light on post-mortem intervals and age at death estimation. However, our
      understanding of intra- and interskeletal proteome variations is currently
      severely limited. Here, we evaluated the proteomes obtained from five distinct
      subsamples of different skeletal elements from buried pig carcasses to ascertain
      the extent of variation within and between individuals. We found that
      reproducibility of data depends on the skeletal element used for sampling and
      that intrabone differences exceed those observed between the same skeletal
      element sampled from different individuals. Interestingly, the abundance of
      several serum proteins appeared to correlate with biological age with relative
      concentrations of alpha-1 antitrypsin and chromogranin-A increasing and those of
      fetuin-A decreasing. We also observed a surprising level of divergence in data
      from different LC-MS/MS runs on aliquots of similar samples analyzed months
      apart, adding constraints to the comparison of results of such methods across
      different studies.

PMID- 28436666
TI  - Addition to "Aryl Fluorosulfate Trapped Staudinger Reduction".

PMID- 28436667
TI  - Construction of 1-Heteroaryl-3-azabicyclo[3.1.0]hexanes by sp3-sp2 Suzuki-Miyaura
      and Chan-Evans-Lam Coupling Reactions of Tertiary Trifluoroborates.
AB  - Compounds that contain the 1-heteroaryl-3-azabicyclo[3.1.0]hexane architecture
      are of particular interest to the pharmaceutical industry yet remain a challenge
      to synthesize. We report herein an expedient and modular approach to the
      synthesis of 1-heteroaryl-3-azabicyclo[3.1.0]hexanes by Suzuki-Miyaura and Chan
      Evans-Lam coupling reactions of tertiary trifluoroborate salts. Our Suzuki
      Miyaura cross-coupling protocol is compatible with a broad range of aryl and
      heteroaryl bromides and chlorides. The unprecedented Chan-Evans-Lam coupling of
      tertiary trifluoroborates allows the facile construction of 1-heteroaryl-3
      azabicyclo[3.1.0]hexanes containing C-tertiary arylamines at the ring juncture.

PMID- 28436668
TI  - Cycloisomerization between Aryl Enol Ether and Silylalkynes under Ruthenium
      Hydride Catalysis: Synthesis of 2,3-Disubstituted Benzofurans.
AB  - Metal-catalyzed cycloisomerization reactions of 1,n-enynes have become
      conceptually and chemically attractive processes in the search for atom economy,
      which is a key subject of current research. However, metal-catalyzed
      cycloisomerization between aryl enol ether and silylalkynes has not been
      developed. The ruthenium hydride complex catalyzed cycloisomerization between
      aryl enol ether and silylalkynes is reported to give benzofurans having useful
      functional groups, vinyl and trimethylsilylmethyl, on the 2- and 3-positions,
      respectively.

PMID- 28436669
TI  - Stereoselective Synthesis of Exocyclic Tetrasubstituted Vinyl Halides via Ru
      Catalyzed Halotropic Cycloisomerization of 1,6-Haloenynes.
AB  - Herein, a ruthenium-catalyzed cycloisomerization that transforms 1,6-haloenynes
      into 5-membered carbo- and heterocycles that bear exocyclic, stereodefined,
      tetrasubstituted vinyl halides is reported. The reaction is insensitive to air
      and water, tolerates a variety of functional groups, and proceeds with good to
      excellent stereoselectivity and yield.

PMID- 28436670
TI  - Enantio- and Stereoselective Construction of Atisane Scaffold via Organocatalytic
      Intramolecular Michael Reaction and Diels-Alder Reaction.
AB  - An enantio- and stereoselective construction of the atisane scaffold via
      organocatalytic intramolecular Michael reaction and Diels-Alder reaction is
      described. The organocatalytic intramolecular Michael reaction has been found to
      stereoselectively generate a trans-stereodiad comprising an all-carbon quaternary
      and a tertiary stereogenic centers. Use of the chiral secondary amine bearing
      thiourea with benzoic acid as additive is the key to obtaining the desired
      product with excellent ee in synthetically acceptable yield. The prepared chiral
      building block has been successfully converted to the compound including the
      atisane scaffold via the highly stereoselective intramolecular Diels-Alder
      reaction.

PMID- 28436671
TI  - Catalytic Asymmetric Cycloadditions of Silyl Nitronates Bearing alpha-Aryl Group.
AB  - 1,3-Dipolar cycloadditions of 2-alkylacroleins or atropaldehyde with
      triisopropylsilyl nitronates bearing an alpha-aryl group produced 3-aryl-2
      isoxazolines having a chiral quaternary center in up to 94% ee and up to 88%
      yield with the aid of Corey's oxazaborolidine catalyst. Specifically, the TIPS
      nitronate with an alpha-(p-methoxyphenyl) group gave mainly the 2-isoxazolines
      having an all-carbon quaternary center.

PMID- 28436672
TI  - Kinetic Energy Density as a Predictor of Hydrogen-Bonded OH-Stretching
      Frequencies.
AB  - This work considers the nature of the intermolecular hydrogen bond in a series of
      15 different complexes with OH donor groups and N, O, P, or S acceptor atoms. To
      complement the existing literature, room-temperature gas-phase vibrational
      spectra of the methanol-pyridine, ethanol-pyridine, and 2,2,2-trifluoroethanol
      pyridine complexes were recorded. These complexes were chosen, as they exhibit
      hydrogen bonds of intermediate strength as compared to previous investigations
      that involved strong or weak hydrogen bonds. Non Covalent Interactions (NCI)
      theory was used to calculate various properties of the intermolecular hydrogen
      bonds, which were compared to the experimental OH-stretching vibrational red
      shifts. We find that the experimental OH-stretching red shifts correlate strongly
      with the kinetic energy density integrated within the reduced density gradient
      volume that describes a hydrogen bond [G(s0.5)]. Given that vibrational red
      shifts are commonly used as a metric of the strength of a hydrogen bond, this
      suggests that G(s0.5) could be used as a predictor of hydrogen bonding strength.

PMID- 28436673
TI  - Unique Rhizosphere Micro-characteristics Facilitate Phytoextraction of Multiple
      Metals in Soil by the Hyperaccumulating Plant Sedum alfredii.
AB  - Understanding the strategies that the roots of hyperaccumulating plants use to
      extract heavy metals from soils is important for optimizing phytoremediation. The
      rhizosphere characteristics of Sedum alfredii, a hyperaccumulator, were
      investigated 6 months after it had been planted in weathered field soils
      contaminated with 5.8 MUg of Cd g-1, 1985.1 MUg of Zn g-1, 667.5 MUg of Pb g-1,
      and 698.8 MUg of Cu g-1. In contrast with the non-hyperaccumulating ecotype
      (NHE), the hyperaccumulating ecotype (HE) of S. alfredii was more tolerant to the
      metals, and higher levels of Cd and Zn accumulated. The HE was characterized by a
      unique rhizosphere, including extensive root systems, a reduced soil pH, a higher
      metal bioavailability, and increased rhizomicrobial activity. The bioavailability
      of metals was significantly correlated with the HE's unique bacterial communities
      (P < 0.005). The HE harbored abundant Streptomyces (9.43%, family
      Streptomycetaceae), Kribbella (1.08%, family Nocardioidaceae), and an
      unclassified genus (1.09%, family Nocardioidaceae) in its rhizosphere, a
      composition that differed from that of the NHE. PICRUSt analysis predicted high
      relative abundances of imputed functional profiles in the HE rhizosphere related
      to membrane transport and amino acid metabolism. This study reveals the
      rhizosphere characteristics, particularly the unique bacterial rhizobiome of a
      hyperaccumulator, that might provide a new approach to facilitating heavy metal
      phytoextraction.

PMID- 28436674
TI  - General Dialdehyde Click Chemistry for Amine Bioconjugation.
AB  - The development of methods for conjugating a range of molecules to primary amine
      functional groups has revolutionized the fields of chemistry, biology, and
      material science. The primary amine is a key functional group and one of the most
      important nucleophiles and bases used in all of synthetic chemistry. Therefore,
      tremendous interest in the synthesis of molecules containing primary amines and
      strategies to devise chemical reactions to react with primary amines has been at
      the core of chemical research. In particular, primary amines are a ubiquitous
      functional group found in biological systems as free amino acids, as key side
      chain lysines in proteins, and in signaling molecules and metabolites and are
      also present in many natural product classes. Due to its abundance, the primary
      amine is the most convenient functional group handle in molecules for ligation to
      other molecules for a broad range of applications that impact all scientific
      fields. Because of the primary amine's central importance in synthetic chemistry,
      acid-base chemistry, redox chemistry, and biology, many methods have been
      developed to efficiently react with primary amines, including activated
      carboxylic acids, isothiocyanates, Michael addition type systems, and reaction
      with ketones or aldehydes followed by in situ reductive amination. Herein, we
      introduce a new traceless, high-yield, fast click-chemistry method based on the
      rapid and efficient trapping of amine groups via a functionalized dialdehyde
      group. The click reaction occurs in mild conditions in organic solvents or
      aqueous media and proceeds in high yield, and the starting dialdehyde reagent and
      resulting dialdehyde click conjugates are stable. Moreover, no catalyst or
      dialdehyde-activating group is required, and the only byproduct is water. The
      initial dialdehyde and the resulting conjugate are both straightforward to
      characterize, and the reaction proceeds with high atom economy. To demonstrate
      the broad scope of this new click-conjugation strategy, we designed a
      straightforward scheme to synthesize a suite of dialdehyde reagents. The
      dialdehyde molecules were used for applications in cell-surface engineering and
      for tailoring surfaces for material science applications. We anticipate the broad
      utility of the general dialdehyde click chemistry to primary amines in all areas
      of chemical research, ranging from polymers and bioconjugation to material
      science and nanoscience.

PMID- 28436675
TI  - Infrared Spectra of Gas-Phase 1- and 2-Propenol Isomers.
AB  - Fourier transform infrared spectra of isolated 1-propenol and 2-propenol in the
      gas-phase have been collected in the range of 900-3800 cm-1, and the absolute
      infrared absorption cross sections reported for the first time. Both cis and
      trans isomers of 1-propenol were observed with the trans isomer in greater
      abundance. Syn and anti conformers of both 1- and 2-propenol were also observed,
      with abundance consistent with thermal population. The FTIR spectrum of the
      smaller ethenol (vinyl alcohol) was used as a benchmark for our computational
      results. As a consequence, its spectrum has been partially reassigned resulting
      in the first report of the anti-ethenol conformer. Electronic structure
      calculations were used to support our experimental results and assign vibrational
      modes for the most abundant isomers, syn-trans-1-propenol and syn-2-propenol.

PMID- 28436676
TI  - Organocatalyzed Direct Aldol Reaction of Silyl Glyoxylates for the Synthesis of
      alpha-Hydroxysilanes.
AB  - A novel organocatalyzed direct aldol reaction of aldehydes to silyl glyoxylates
      is disclosed. This method provides an efficient route to alpha-hydroxysilanes
      with excellent enantioselectivities (up to 99% ee) and high
      diastereoselectivities (up to >20:1 dr). In the new activation model of silyl
      glyoxylates, the hydrogen bond is critical to the reaction. A carbonyl group
      directly attached to silicon in acylsilanes could be activated by coordination to
      the proton of hydroxyl and carboxylic acid via a hydrogen bond. Moreover,
      commercially available cis-l-4-hydroxyproline is an ideal organocatalyst for
      activating both aldehydes and acylsilanes.

PMID- 28436677
TI  - Stereoselective Total Synthesis of Carolacton.
AB  - A short and convergent strategy for the stereoselective total synthesis of
      biologically active natural product carolacton has been accomplished. Our
      synthesis highlights the Urpi acetal aldol, Crimmins aldol, Ireland-Claisen
      rearrangement, TiCl4-assisted aldol followed by beta-hydroxy elimination to
      construct C7-C8 olefin, and ring-closing metathesis as the key steps for
      achieving the target molecule with an overall yield of 18.8%.

PMID- 28436678
TI  - Nanotoxicity modelling and removal efficiencies of ZnONP.
AB  - In this paper the aim is to investigate the toxic effect of zinc oxide
      nanoparticles (ZnONPs) and is to analyze the removal of ZnONP in aqueous medium
      by the consortium consisted of Daphnia magna and Lemna minor. Three separate test
      groups are formed: L. minor ([Formula: see text]), D. magna ([Formula: see
      text]), and L. minor + D. magna ([Formula: see text]) and all these test groups
      are exposed to three different nanoparticle concentrations ([Formula: see text]).
      Time-dependent, concentration-dependent, and group-dependent removal efficiencies
      are statistically compared by non-parametric Mann-Whitney U test and
      statistically significant differences are observed. The optimum removal values
      are observed at the highest concentration [Formula: see text] for [Formula: see
      text], [Formula: see text] for [Formula: see text]and [Formula: see text] for
      [Formula: see text] and realized at [Formula: see text] for all test groups
      [Formula: see text]. There is no statistically significant differences in removal
      at low concentrations [Formula: see text] in terms of groups but [Formula: see
      text] test groups are more efficient than [Formula: see text] test groups in
      removal of ZnONP, at [Formula: see text] concentration. Regression analysis is
      also performed for all prediction models. Different models are tested and it is
      seen that cubic models show the highest predicted values (R2). In toxicity
      models, R2 values are obtained at (0.892, 0.997) interval. A simple solution
      phase method is used to synthesize ZnO nanoparticles. Dynamic Light Scattering
      and X-Ray Diffraction (XRD) are used to detect the particle size of synthesized
      ZnO nanoparticles.

PMID- 28436679
TI  - CITED2 Mutations in Conserved Regions Contribute to Conotruncal Heart Defects in
      Chinese Children.
AB  - Conotruncal heart defects (CTDs) are severe malformations of outflow tract with
      heterogeneous morphology. Several missense variants of CITED2 have been
      identified to cause CTDs in recent researches. In this study, we screened the
      coding regions of CITED2 in 605 Chinese children with CTDs and found two possible
      pathogenic mutant sites: p.Q117L and p.T257A, both located in the conserved
      regions of CITED2. Then, we investigated the biological and functional
      alterations of them. Western blotting showed low level of protein expression of
      mutant Q117 and T257A compared with wild-type CITED2. Dual-luciferase reporter
      assay demonstrated that mutant Q117 and T257A decreased the ability of CITED2 to
      modulate the expression of paired-like homeodomain transcription factor 2 gamma
      (PITX2C), which are closely related to cardiac growth and left-right patterning.
      Meanwhile, T257A also exhibited impaired ability to mediate vascular endothelial
      growth factor expression, another gene closely associated with the normal
      development of cardiovascular system. Three-dimensional molecular conformation
      showed reduced hydrogen bond between Asp254 and mutant Thr257, indicating the
      weakened stability and binding ability of CITED2. All these results suggest that
      CITED2 mutations in conserved regions lead to disease-causing biological and
      functional changes and may contribute to the occurrence of CTDs.

PMID- 28436680
TI  - Extracting Optical Fiber Background from Surface-Enhanced Raman Spectroscopy
      Spectra Based on Bi-Objective Optimization Modeling.
AB  - We propose a bi-objective optimization model for extracting optical fiber
      background from the measured surface-enhanced Raman spectroscopy (SERS) spectrum
      of the target sample in the application of fiber optic SERS. The model is built
      using curve fitting to resolve the SERS spectrum into several individual bands,
      and simultaneously matching some resolved bands with the measured background
      spectrum. The Pearson correlation coefficient is selected as the similarity index
      and its maximum value is pursued during the spectral matching process. An
      algorithm is proposed, programmed, and demonstrated successfully in extracting
      optical fiber background or fluorescence background from the measured SERS
      spectra of rhodamine 6G (R6G) and crystal violet (CV). The proposed model not
      only can be applied to remove optical fiber background or fluorescence background
      for SERS spectra, but also can be transferred to conventional Raman spectra
      recorded using fiber optic instrumentation.

PMID- 28436681
TI  - Psychometric validation of the Geriatric Suicide Ideation Scale (GSIS) among
      older adults with bipolar disorder.
AB  - OBJECTIVES: Across age groups, bipolar disorder (BD) carries the greatest risk of
      death by suicide of all psychiatric conditions; 25%-50% of those with BD will
      make one or more suicide attempt. Psychometrically sound instruments are required
      to reliably measure suicide ideation and risk of self-harm for older adults with
      BD. For this study, we validate the geriatric suicide ideation scale (GSIS) with
      adults 50+ years with BD. METHODS: We recruited a global sample of 220 older
      adults with BD (M = 58.50 years of age) over 19 days using socio-demographically
      targeted, social media advertising and online data collection. To demonstrate the
      construct validation of GSIS responses by older adults with BD, we computed
      correlations and performed regression analyses to identify predictors of suicide
      ideation. RESULTS: Our analyses support a four-factor model of responses to the
      GSIS (ideation, death ideation, loss of personal and social worth, and perceived
      meaning in life) measuring a higher order latent construct. Older adults with BD
      reporting low satisfaction with life and current depressive symptoms, and who
      misuse alcohol, report significantly higher levels of suicide ideation. Sleep
      quality and cognitive failures are also correlated with GSIS responses.
      CONCLUSIONS: Results support the factorial validity of the GSIS with older adults
      with BD. Similar to other populations, the GSIS measures a four-factor structure
      of suicide ideation. Across BD subtypes, the GSIS appears to reliably measure
      suicide ideation among older adults with BD.

PMID- 28436682
TI  - Kinetics, biochemical and factorial analysis of chromium uptake in a multi-ion
      system by Tradescantia pallida (Rose) D. R. Hunt.
AB  - Discharge of wastewater from electroplating and leather industries is a major
      concern for the environment due to the presence of toxic Cr6+ and other ions,
      such as sulfate, nitrate, phosphate, etc. This study evaluated the potential of
      Tradescantia pallida, a plant species known for its Cr bioaccumulation, for the
      simultaneous removal of Cr6+, SO42-, NO3-, and PO43-. The effect of different co
      ions on Cr6+ removal by T. pallida was examined following the Plackett-Burman
      design of experiments carried out under batch hydroponics conditions. The results
      revealed a maximum removal of 84% Cr6+, 87% SO42-, 94% NO3- and 100% PO43-
      without any phytotoxic effect on the plant for an initial Cr6+ concentration in
      the range 5-20 mg L-1. SO42- and NO3- enhanced Cr uptake at a high initial Cr
      concentration (20 mg L-1), whereas PO43- did not affect Cr uptake both at high
      and low initial Cr concentrations. The Cr6+ removal kinetics in the presence of
      different ions was well described by the pseudo-second-order kinetic model which
      revealed that both biosorption and bioaccumulation of the metal played an
      important role in Cr6+ removal. Increase in the total carbohydrate and protein
      content of the plant following Cr6+ and co-ions exposure indicated a good
      tolerance of the plant toward Cr6+ toxicity. Furthermore, enhancement in the
      lipid peroxidation and catalase activity in T. pallida upon Cr6+ exposure
      revealed a maximum stress-induced condition in the plant. Overall, this study
      demonstrated a very good potential of the plant T. pallida for Cr6+ removal from
      wastewater even in the presence of co-ions.

PMID- 28436683
TI  - Dexmedetomidine Protects PC12 Cells from Lidocaine-Induced Cytotoxicity Through
      Downregulation of COL3A1 Mediated by miR-let-7b.
AB  - Safety concerns of some local anesthetics, such as lidocaine, have been raised in
      recent years due to potential neurological impairment. Dexmedetomidine may
      protect humans from neurotoxicity, and miR-let-7b is activated by nerve injury;
      however, the roles of miR-let-7b and its target gene in lidocaine-induced
      cytotoxicity are not well known. Through bioinformatics and a luciferase reporter
      assay, COL3A1 was suggested as a direct target gene of miR-let-7b. Here, we
      confirmed by measuring mRNA and protein levels that miR-let-7b was downregulated
      and COL3A1 was upregulated in lidocaine-treated cells, an observation that was
      reversed by dexmedetomidine. Similar to miR-let-7b mimics or knockdown of COL3A1,
      dexmedetomidine treatment reduced the expression of COL3A1, suppressed cell
      apoptosis and cell migration/invasion ability, and induced cell cycle progression
      and cell proliferation in PC12 cells, effects that were reversed by the miR-let
      7b inhibitor. Meanwhile, proteins involved in cell apoptosis, such as Bcl2 and
      caspase 3, were impacted as well. Taken together, dexmedetomidine may protect
      PC12 cells from lidocaine-induced cytotoxicity through miR-let-7b and COL3A1,
      while also increasing Bcl2 and inhibiting caspase 3. Therefore, miR-let-7b and
      COL3A1 might play critical roles in neuronal injury, and they are potential
      therapeutic targets.

PMID- 28436685
TI  - Factors affecting the performance of horizontal flow constructed treatment
      wetland vegetated with Cyperus papyrus for municipal wastewater treatment.
AB  - The effect of hydraulic loading rate (HLR) and hydraulic retention time (HRT) on
      the bioremediation of municipal wastewater using a pilot scale subsurface
      horizontal flow constructed treatment wetland (HFCTW) vegetated with Cyprus
      papyrus was investigated. Different HLRs were applied to the treatment system
      namely 0.18, 0.10, and 0.07 m3/m2. d with corresponding HRTs of 1.8, 3.2, and 4.7
      days, respectively. The flow rate was 8 m3/d, and the average organic loading
      rate (OLR) was 0.037 kg BOD/m3/d. Results showed that the performance of the
      HFCTW was linearly affected by decreasing the HLR and increasing the HRT. The
      highest treatment efficiency was achieved at HRT (4.7 days) and HLR (0.07 m3/m2.
      d). The percentage reductions of chemical oxygen demand (COD), biochemical oxygen
      demand (BOD), and total suspended solids (TSS) were 86%, 87%, and 80%,
      respectively. Satisfactory nutrient removal was obtained. Also, removal of 2-3
      logs of bacterial indicators of pollution was achieved. The dry biomass of
      Cyperus was 7.7 kg/m2 and proved to be very efficient in nitrification processes
      due to high diversity of the roots that increase the treatment surface area.

PMID- 28436684
TI  - Serenoa repens for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia:
      Current Evidence and Its Clinical Implications in Naturopathic Medicine.
AB  - OBJECTIVES: Benign prostatic hyperplasia (BPH) commonly affects men above 40
      years old. The progression of BPH is often accompanied with lower urinary tract
      symptoms (LUTS) that can significantly affect the quality of life of the
      patients. Serenoa repens (saw palmetto) is a popular herbal remedy indicated for
      LUTS/BPH. We reviewed the current research on the efficacy of S. repens on
      LUTS/BPH as a monotherapy as well as combination therapies. DESIGN: Non
      systematic searches were performed in PubMed for human studies and systematic
      reviews on the topic. RESULTS: The latest evidence, based largely on the Cochrane
      review, suggests that S. repens is not superior to placebo in treating LUTS/BPH
      as a monotherapy, even at double and triple doses. Initial clinical trials on
      treatment of LUTS/BPH using S. repens with lycopene and selenium, as well as S.
      repens with Urtica Dioica, have shown positive results. S. repens is safe in its
      application. However, there is a high level of heterogeneity in the quality of S.
      repens products. We suggest that strong placebo effect, potentially influenced by
      positive patients' expectation on S. repens, shapes both the clinical practice
      outcomes and the findings of clinical trials. Hitherto, the totality of evidence
      continues to suggest that S. repens is a prudent therapeutic option as part of
      the naturopathic treatment for LUTS/BPH. CONCLUSIONS: The totality of evidence
      includes favorable patients' response from clinical experience, impact of placebo
      effect, early positive studies, subjective nature of symptom reporting,
      pharmacological properties of S. repens, and potential synergistic effects when
      combined with other therapies.

PMID- 28436686
TI  - Sparking Thinking: Studying Modern Precision Medicine Will Accelerate the
      Progression of Traditional Chinese Medicine Patterns.
AB  - Incorporating "-omics" studies with environmental interactions could help
      elucidate the biological mechanisms responsible for Traditional Chinese Medicine
      (TCM) patterns. Based on the authors' own experiences, this review outlines a
      model of an ideal combination of "-omics" biomarkers, environmental factors, and
      TCM pattern classifications; provides a narrative review of the relevant genetic
      and TCM studies; and lists several successful integrative examples. Two
      integration tools are briefly introduced. The first is the integration of modern
      devices into objective diagnostic methods of TCM patterning, which would improve
      current clinical decision-making and practice. The second is the use of biobanks
      and data platforms, which could broadly support biological and medical research.
      Such efforts will transform current medical management and accelerate the
      progression of precision medicine.

PMID- 28436687
TI  - Cytotoxic flavonoids from the fruits of Derris indica.
AB  - Chemical investigation of the ethyl acetate extract from the fruits of Derris
      indica has led to the isolation of a new furanoflavonoid derivative, 4'
      hydroxypinnatin (1), and five known compounds. Pinnatin (2) showed strong
      cytotoxicity against cholangiocarcinoma (KKU-100) and human hepatoma (HepG2) cell
      lines with IC50 values of 6.0 +/- 2.7 and 9.0 +/- 4.1 MUg/ml, respectively, and
      showed maximal cell killing effect of about 88-90%. Flavone 5 exhibited the most
      cytotoxicity against KKU-100 but it showed moderate efficacy (Emax = 50.7%).

PMID- 28436688
TI  - A Vibrational Circular Dichroism Microsampling Accessory: Mapping Enhanced
      Vibrational Circular Dichroism in Amyloid Fibril Films.
AB  - We report the first vibrational circular dichroism (VCD) measurement of spatial
      heterogeneity in a sample using infrared (IR) microsampling. Vibrational circular
      dichroism spectra are typically measured using a standard IR cell with an IR beam
      diameter of 10 mm or greater making it impossible to investigate the spatial
      heterogeneity of a solid film sample. We have constructed a VCD sampling assembly
      with either 3 mm or 1 mm spatial resolution. An XY-translation stage was used to
      measure spectra at different spatial locations producing IR and VCD maps of the
      sample. In addition, a rotating sample stage was employed using a dual
      photoelastic modulator (PEM) setup to suppress artifacts due to linear
      birefringence in solid-phase or film samples. Infrared and VCD mapping of an
      insulin fibril film has been carried out at both 3 and 1 mm spatial resolution,
      and lysozyme films were mapped at 1 mm resolution. The IR spectra of different
      spots vary in intensity due primarily to sample thickness. The changes in the VCD
      intensity across the map largely correlate to corresponding changes in the IR
      map. Closer inspection of the insulin map revealed changes in the relative
      intensities of the VCD spectra not present in the parent IR spectra, which
      indicated differences in the degree of supramolecular chirality of the fibrils in
      the various spatial regions. For lysozyme films, in addition to different degrees
      of supramolecular chirality, reversal of the net fibril chirality was observed.
      The large signal-to-noise ratio observed at 1 mm resolution implies the
      feasibility of further increasing the spatial resolution by one or two orders of
      magnitude for protein fibril film samples.

PMID- 28436689
TI  - The Mentalization Scale (MentS): A Self-Report Measure for the Assessment of
      Mentalizing Capacity.
AB  - The psychometric properties of a new 28-item self-report measure of
      mentalization, the Mentalization Scale (MentS), were examined in 2 studies: with
      a sample of employed adults and university students (N1 = 288 + 278) and with a
      sample of persons with borderline personality disorder (BPD) and matched controls
      (N2 = 62 + 62). Besides the MentS, both studies employed measures of attachment
      and the Big Five; Study 1 also included assessments of empathy and emotional
      intelligence. MentS whole-scale internal consistency was good in the community
      and acceptable in the clinical sample (alpha = .84 and .75, respectively). A
      principal components analysis of Study 1 data yielded 3 interpretable factors, or
      subscales: Self-Related Mentalization (MentS-S), Other-Related Mentalization
      (MentS-O), and Motivation to Mentalize (MentS-M). These showed acceptable
      reliabilities (alpha = .74-.79), except for MentS-M in the clinical sample (alpha
      = .60). MentS scores further exhibited a coherent pattern of correlations with
      cognate constructs and the Big Five, relating positively to empathy, trait and
      ability emotional intelligence, openness, extraversion, and conscientiousness,
      and negatively to attachment avoidance and anxiety, and neuroticism. Persons with
      BPD scored significantly lower on MentS total and MentS-S. The proposed scale is
      thus deemed suitable for quick, yet meaningful, assessments of mentalization in
      both individual differences research and clinical contexts.

PMID- 28436690
TI  - A Comparison of the Nomological Networks Associated With Forced-Choice and Likert
      Formats of the Narcissistic Personality Inventory.
AB  - The Narcissistic Personality Inventory (NPI) is one of the most popular measures
      of narcissism. However, its use of a forced-choice response set might negatively
      affect some of its psychometric properties. The purpose of this research was to
      compare a Likert version of the NPI, in which only the narcissistic response of
      each pair was given, to the original NPI, in 3 samples of participants (N =
      1,109). To this end, we compared the nomological networks of the forced-choice
      and Likert formats of the NPI in relation to alternative measures of narcissism,
      narcissistic personality disorder, entitlement, self-esteem, general personality
      traits (reported by self and informants), interpersonal styles, and general
      pathological traits included in the DSM-5. The Likert format NPI-total and
      subscales-manifested similar construct validity to the original forced-choice
      format across all criteria with only minor differences that seem to be due mainly
      to the increased reliability and variability found in the Likert NPI
      Entitlement/Exploitativeness subscale. These results provide evidence that a
      version of the NPI that employs a Likert format can justifiably be used in place
      of the original.

PMID- 28436691
TI  - Concise synthesis and PTP1B inhibitory activity of (R)- and (S)
      dihydroresorcylide.
AB  - The present study was designed to develop a concise synthetic route for
      macrolide, with the purpose of confirming the absolute configuration of natural
      dihydroresorcylide (1) and making it more easily accessible for biological
      evaluation. The absolute configuration of C-3 in natural 1 was revised to be R by
      comparison of the rotation sign of synthetic (R)- and (S)-1. The synthetic (R)-1
      was found to be a novel highly specific PTP1B inhibitor with an IC50 value of
      17.06 MUM.

PMID- 28436692
TI  - Rhizospheric soil enzyme activities and phytominimg potential of Aeluropus
      lagopoides and Cyperus conglomeratus growing in contaminated soils at the banks
      of artificial lake of reclaimed wastewater.
AB  - This work investigates the phytoremediation potential of Aeluropus lagopoides and
      Cyperus conglomeratus, growing indigenously in the vicinity of an artificial lake
      of reclaimed water in Tabuk, Saudi Arabia . The sampling sites were located at
      different distances from the wastewater treatment plants. Trace metal contents
      were higher in roots than shoots in both these plants. Soil urease activity in
      rhizophere increased linearly along the sampling sites, however, soil alkaline
      phosphatase and beta-glucosidase activities were higher at site 2 but at site 3,
      the activities of both these soil enzymes reduced. Significant correlations were
      observed between soil urease activity and the bioconcentration factor (BCF) of
      Cd, Cu, Pb, and As in A. lagopoides and translocation factor (TF) for all metals
      in both these plants. Soil beta-glucosidase activity was negatively correlated
      with the TF of Cd, Cu, Pb, and As in A. lagopoides and positively in C.
      conglomeratus, respectively. Higher BCF of Cd, Cu and Pb than C. conglomeratus
      and suitable for phytostabilization, however at site 3, C. conglomeratus showed
      better phytostabilization efficiency for As, as the BCF of As was higher than the
      A. lagopoides. On the basis of metal accumulation efficiency and rhizospheric
      soil urease and beta-glucosidase activities, A. lagopoides species proved to be a
      better option for application in phytostabilization strategy than C.
      conglomeratus plants in the area surrounding the artificial lake of reclaimed
      water in Tabuk, Saudi Arabia.

PMID- 28436693
TI  - Expression of Circulating miR-17-92 Cluster and HDAC9 Gene in Atherosclerotic
      Patients with Unstable and Stable Carotid Plaques.
AB  - AIMS: The miR-17-92 cluster and the HDAC9 gene are involved in inflammatory,
      apoptotic, and angiogenic processes that are activated in the vulnerable carotid
      plaque. The aim of this research was to determine whether expression of one or
      more of the miRs of the miR-17-92 cluster and/or HDAC9 expression could represent
      biomarkers for patients with unstable atherosclerotic carotid plaques. MATERIALS
      AND METHODS: Plasma levels of miRs and HDAC9 expression in peripheral blood were
      analyzed by real-time PCR in patients with histologically classified stable or
      unstable plaques. RESULTS: No differences were observed between the two groups.
      DISCUSSION AND CONCLUSIONS: Levels of the miR-17-92 cluster in plasma and HDAC9
      gene expression in peripheral blood cannot be considered appropriate biomarkers
      to identify patients with unstable plaques at risk of rupture.

PMID- 28436694
TI  - Acculturation level and caregiver outcomes from a randomized intervention trial
      to enhance caregivers' health: evidence from REACH II.
AB  - OBJECTIVE: Latinos comprise a growing segment of the caregiver population and
      vary widely in acculturation, yet little is known regarding how acculturation
      might affect caregiver stress or intervention outcomes. This study examined the
      relationship between acculturation and burden, bother, and depression in Latino
      dementia caregivers at baseline and following an intervention. METHODS: This was
      a secondary data analysis of 211 Latino caregivers of older adults with dementia
      from Resources for Enhancing Alzheimer's Caregiver Health (REACH) II, a multisite
      randomized trial of caregiver interventions. Baseline and follow-up data were
      used to run mixed-effects models examining the main and moderating effect of
      acculturation on caregiver stress. RESULTS: No significant main effect of
      acculturation was found for any of the outcome measures, controlling for
      demographic covariates. Acculturation moderated the effect of the intervention on
      caregiver burden: those who were more acculturated benefited more from the
      intervention. CONCLUSION: Differential acculturation for Latino caregivers was
      not directly associated with caregiver burden, bother, or depression, but was
      associated with reducing burden from the intervention. Future research should
      explore by what mechanism acculturation influences caregiver burden following an
      intervention.

PMID- 28436695
TI  - The impact of childhood parental quality on mental health outcomes in older
      adults.
AB  - OBJECTIVE: Parental bonding is cited as a determinant of mental health outcomes
      in childhood, adolescence and early-mid adulthood. Examination of the long-term
      impact for older adults is limited. We therefore examine the long-term risk of
      perceived poor parental bonding on mental health across the lifespan and into
      early-old age. METHODS: Participants (N = 1255) were aged 60-64 years of age and
      drawn from the Australian Life Histories and Health study. Quality of parental
      bonding was assessed with the Parental Bonding Instrument (PBI). Self-reported
      history of doctors' mental health diagnoses and current treatment for each
      participant was recorded. Current depression was assessed with the Centre for
      Epidemiologic Studies Depression-8 (CESD-8). Due to known gender differences in
      mental health rates across the lifespan, analyses were stratified by sex.
      RESULTS: A bi-factor analysis of the PBI in a structural equation framework
      indicated perceived Poor Parental Quality as a risk for both ever and current
      depression for both sexes. For males, Over-Protective Fathers were a risk for
      ever and current depression, whilst overall Poor Parental Quality was a risk for
      reporting current depression treatment. Whilst a number of the risks associated
      with current depression and treatment were attenuated when controlling for
      current mood, parental quality remained a significant risk for having reported a
      lifetime diagnosis for depression and anxiety for men. CONCLUSION: Our results
      extend the existing literature base and demonstrate that mental health risk
      attributed to poor perceived parental quality continues across the life-course
      and into early-old age.

PMID- 28436696
TI  - Corrections.

PMID- 28436697
TI  - Liver Track Embolization After Islet Cell Transplant: Comparison of Two
      Techniques.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy and safety of
      microfibrillar collagen paste with those of gelatin sponge for liver track
      embolization after islet cell transplants. MATERIALS AND METHODS: In a single
      institution, retrospective study, 37 patients underwent 66 islet cell transplants
      from January 2005 through October 2015. Transplants were performed with 6-French
      transhepatic access, systemic anticoagulation, pretransplant and posttransplant
      portal venous pressure measurement, and image-guided liver track embolization
      with gelatin sponge (2005-2011) or microfibrillar collagen paste (2012-2015). The
      findings on 20 patients (two men, 18 women; mean age, 48 years) who underwent 35
      gelatin sponge embolizations were compared with the findings on 13 patients (six
      men, seven women; mean age, 48 years) who underwent 22 microfibrillar collagen
      paste embolizations (four patients, nine procedures without embolization
      excluded). Medical record review was used to compare laboratory test results,
      portal venous pressures, and 30-day adverse bleeding events (classified according
      to Society of Interventional Radiology and Bleeding Academic Research Consortium
      criteria) between groups. RESULTS: The technical success rates were 100% in the
      microfibrillar collagen paste group and 91% in the gelatin sponge group. Group
      characteristics were similar, there being no differences in platelet count,
      partial thromboplastin time, or number of islet cell transplants per patient (p >
      0.05). A statistical difference in international normalized ratio (1.0 versus
      1.1) was not clinically significant (p = 0.012). Posttransplant portal venous
      pressure was slightly higher among patients treated with gelatin sponge (13
      versus 9 mm Hg, p = 0.002). No bleeding occurred after microfibrillar collagen
      paste embolization, whereas nine bleeding events followed gelatin sponge
      embolization (0% versus 26%, p = 0.020). In univariate comparison of bleeding and
      nonbleeding groups, the use of gelatin sponge was statistically associated with
      postprocedure hemorrhage. CONCLUSION: Microfibrillar collagen paste is effective
      and safe for liver track embolization to prevent bleeding after islet cell
      transplants. It appears to be more efficacious than gelatin sponge.

PMID- 28436698
TI  - Systematic Review Classification.

PMID- 28436699
TI  - Reflecting on the Past and Looking to the Future in Pediatric Imaging.

PMID- 28436700
TI  - An Approach to the Evaluation of Incidentally Identified Bone Lesions Encountered
      on Imaging Studies.
AB  - OBJECTIVE: This article discusses the strengths and weaknesses of the various
      anatomic and molecular imaging techniques in the evaluation of unexpected bone
      lesions. CONCLUSION: An approach to the imaging evaluation of chondroid,
      osteoblastic, and osteolytic lesions as well as focal marrow abnormalities is
      reviewed.

PMID- 28436701
TI  - Two cytotoxic 6,7-seco-spiro-lacton-ent-kauranoids from Isodon rubescens.
AB  - The present study was performed to investigate the chemical components of the
      branches and leaves of Isodon rubescens. Two 6,7-seco-spiro-lacton-ent-kauranoids
      were obtained. Based on the extensive spectroscopic analyses, their structures
      were elucidated as 6-epi-11-O-acetylangustifolin (1) and 11-O-acetylangustifolin
      (2), respectively. The structure of 2 was further comfirmed by X-ray
      crystallography analysis. MTT method was employed to evaluate their cytotoxity
      against human lung cancer cell lines A549 and leukemia cell lines K562.

PMID- 28436702
TI  - A novel matrix dispersion based on phospholipid complex for improving oral
      bioavailability of baicalein: preparation, in vitro and in vivo evaluations.
AB  - Phospholipid complex is one of the most successful approaches for enhancing oral
      bioavailability of poorly absorbed plant constituents. But the sticky property of
      phospholipids results in an unsatisfactory dissolution of drugs. In this study, a
      matrix dispersion of baicalein based on phospholipid complex (BaPC-MD) was first
      prepared by a discontinuous solvent evaporation method, in which
      polyvinylpyrrolidone-K30 (PVP-K30) was employed for improving the dispersibility
      of baicalein phospholipid complex (BaPC) and increasing dissolution of baicalein.
      The combination ratio of baicalein and phospholipids in BaPC-MD was 99.39% and
      baicalein was still in a complete complex state with phospholipid in BaPC-MD.
      Differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning
      electron microscopy (SEM) and Fourier Transform Infrared (FTIR) analyzes
      demonstrated that baicalein was fully transformed to an amorphous state in BaPC
      MD and phospholipid complex formed. The water-solubility and n-octanol solubility
      of baicalein in BaPC-MD significantly increased compared with those of pure
      baicalein. Compared with baicalein and BaPC, the cumulative dissolution of BaPC
      MD at 120 min increased 2.77- and 1.23-fold, respectively. In vitro permeability
      study in Caco-2 cells indicated that the permeability of BaPC-MD was remarkably
      higher than those of baicalein and BaPC. Pharmacokinetic study showed that the
      average Cmax of BaPC-MD was significantly increased compared to baicalein and
      BaPC. AUC0-14 h of BaPC-MD was 5.01- and 1.91-fold of baicalein and BaPC,
      respectively. The novel BaPC-MD significantly enhanced the oral bioavailability
      of baicalein by improving the dissolution and permeability of baicalein without
      destroying the complexation state of baicalein and phospholipids. The current
      drug delivery system provided an optimal strategy to significantly enhance oral
      bioavailability for poorly water-soluble drugs.

PMID- 28436703
TI  - In the Driver's Seat: Development and Implementation of an e-Learning Module on
      Return-to-Driving After Stroke.
AB  - Gaps exist in the knowledge of return-to-driving guidelines, and education is
      needed for Australian health professionals working in the field of stroke. In
      this paper, authors evaluate the implementation of an e-learning module. A pre-
      and post-module knowledge test and survey were used to assess the e-module's
      success in achieving its learning objectives. Initially, 204 learners completed
      the module, with 68% of learners scoring 100% in the post-module knowledge test.
      Only 12 learners completed the survey. The authors recommend that health
      professionals other than occupational therapists access this e-module, and a
      review on e-module structure is required to improve results of knowledge tests.

PMID- 28436704
TI  - Association of CAT-262C/T with the concentration of catalase in seminal plasma
      and the risk for male infertility in Algeria.
AB  - Catalase (CAT) plays a central role in the protection of different cell types
      against the deleterious effects of hydrogen peroxide. In human, CAT is implicated
      in many physiological and pathological conditions including idiopathic male
      infertility. In this study we examined the association between CAT levels in
      seminal plasma with different sperm parameters and with CAT-262 C/T polymorphism
      and their risk for idiopathic male infertility in Algeria. Semen and blood
      samples were obtained from 111 infertile males and 104 fertile controls from the
      region of Eastern Algeria following informed consent. Standard semen parameters,
      DNA integrity, and CAT concentration in seminal plasma were evaluated. CAT-262C/T
      genotypes were screened using allele specific PCR. Seminal CAT activity was
      significantly different (p<0.0001) between infertile males and controls, it was
      also markedly decreased in oligo-astheno-teratozoospermia (p<0.0001), azoospermia
      (p<0.0001), and normozoospermia (p=0.045) subgroups compared to controls.
      Positive correlations between CAT activity and semen parameters (volume,
      motility, concentration, and morphology) were detected, but not with sperm DNA
      integrity. There was no direct association between CAT-262C/T polymorphism and
      general male infertility. However, the results presented in this study showed
      that CAT activity is remarkably associated with the CAT-262T allele (p=0.001) and
      the different CAT-262C/T genotypes. This study highlighted the major differences
      in the seminal plasma CAT content between infertile and fertile males and the
      differences of CAT concentration between different CAT-262C/T genotypes carriers.

PMID- 28436705
TI  - Pharmacologically increasing collateral perfusion during acute stroke using a
      carboxyhemoglobin gas transfer agent (SanguinateTM) in spontaneously hypertensive
      rats.
AB  - Similar to patients with chronic hypertension, spontaneously hypertensive rats
      (SHR) develop fast core progression during middle cerebral artery occlusion
      (MCAO) resulting in large final infarct volumes. We investigated the effect of
      SanguinateTM (SG), a PEGylated carboxyhemoglobin (COHb) gas transfer agent, on
      changes in collateral and reperfusion cerebral blood flow and brain injury in SHR
      during 2 h of MCAO. SG (8 mL/kg) or vehicle ( n = 6-8/group) was infused i.v.
      after 30 or 90 min of ischemia with 2 h reperfusion. Multi-site laser Doppler
      probes simultaneously measured changes in core MCA and collateral flow during
      ischemia and reperfusion using a validated method. Brain injury was measured
      using TTC. Animals were anesthetized with choral hydrate. Collateral flow changed
      little in vehicle-treated SHR during ischemia (-8 +/- 9% vs. prior to infusion)
      whereas flow increased in SG-treated animals (29 +/- 10%; p < 0.05). In addition,
      SG improved reperfusion regardless of time of treatment; however, brain injury
      was smaller only with early treatment in SHR vs. vehicle (28.8 +/- 3.2% vs. 18.8
      +/- 2.3%; p < 0.05). Limited collateral flow in SHR during MCAO is consistent
      with small penumbra and large infarction. The ability to increase collateral flow
      in SHR with SG suggests that this compound may be useful as an adjunct to
      endovascular therapy and extend the time window for treatment.

PMID- 28436706
TI  - Tobacco Use and Attachment Style in Appalachia.
AB  - Tobacco has been recognized as the number one cause of preventable death in
      America and results in almost 5.2 million years of potential life lost each year.
      The use of tobacco products is highly correlated with pulmonary disease,
      cardiovascular disease, and other forms of chronic illness in America. New
      tobacco products are trending in the tobacco market such as the water pipe/hookah
      and e-cigarettes. With e-cigarettes and other newer forms of tobacco on the rise,
      it is important to look at the underlying factors for using all kinds of tobacco
      products as a means of prevention. Certain adult attachment styles (secure,
      preoccupied, dismissing-avoidant, and fearful-avoidant) in emotionally meaningful
      relationships could be indicators for physical illness, mental illness, and even
      addiction. This study investigated whether or not there is a relationship between
      tobacco use and attachment style. Based on a university-wide survey that was sent
      out at a university in Appalachia with 522 participants, demographic data
      revealed 68.5% (n = 358) did not currently use tobacco products. Of those who did
      currently use tobacco products 54.5% (n = 90) were male, 84.8% (n = 140) were
      undergraduate students, and 66.7% (n = 110) were between the ages of 18-25. For
      individuals who used tobacco 23.5% (n = 38) were in the secure attachment group,
      27.8% (n = 45) were in the dismissing-avoidant attachment group, 30.2% (n = 49)
      were in the fearful-avoidant attachment group, and 18.5% (n = 30) were in the
      preoccupied attachment group. Chi Square analysis demonstrated that attachment
      style was significantly (p < 0.001) different between tobacco users and non-users
      revealing that there is a possibility for prevention of smoking initiation
      through the development of a secure attachment style.

PMID- 28436708
TI  - A novel in vitro ELISA for estimation of glycoprotein content in human rabies
      vaccines.
AB  - In vitro methods for quantification of immunodominant glycoprotein in the rabies
      vaccine formulations serve as good alternative to the cumbersome and variable
      mice potency assay as a batch release test for the vaccine. The present study
      presents the development of a sandwich ELISA with optimal concentrations of a
      high affinity recombinant diabody (D06) and a specific monoclonal antibody (M5B4)
      against rabies glycoprotein for its quantification in the vaccine formulations.
      The glycoprotein estimate correlated linearly (r2 = 0.8) to the in vivo potency
      estimate for the vaccine formulations. This ELISA promises a good forecast of the
      mice potency values and thereby can serve as a simple, yet effective batch
      release test for the rabies vaccines replacing the in vivo assay.

PMID- 28436709
TI  - Transitioning From Occupational Therapy Student To Practicing Occupational
      Therapist: First Year of Employment.
AB  - This research examined the transition from occupational therapy student to
      practicing occupational therapist over the course of one's first year of
      professional employment, as recalled by a sample of occupational therapists.
      Surveys were mailed to 500 occupational therapists randomly selected from
      membership in the American Occupational Therapy Association resulting in 202
      returned surveys. Median year of graduation was 1998, ranging from 1967 to 2014.
      In general, respondents indicated the transition was positive. Having a mentor
      was related to high job satisfaction and good clinical fit, while supervising an
      occupational therapy assistant and low self-confidence were viewed as negative
      impact factors. Recent graduates presented with lower ratings of a positive
      transition and higher ratings of likelihood of experiencing burnout and initial
      job stress than earlier graduates. Recommendations for improving the transition
      experience are presented.

PMID- 28436707
TI  - SAMHD1 protects cancer cells from various nucleoside-based antimetabolites.
AB  - Recently, we demonstrated that sterile alpha motif and HD domain containing
      protein 1 (SAMHD1) is a major barrier in acute myelogenous leukemia (AML) cells
      to the cytotoxicity of cytarabine (ara-C), the most important drug in AML
      treatment. Ara-C is intracellularly converted by the canonical dNTP synthesis
      pathway to ara-CTP, which serves as a substrate but not an allosteric activator
      of SAMHD1. Using an AML mouse model, we show here that wild type but not
      catalytically inactive SAMHD1 reduces ara-C treatment efficacy in vivo. Expanding
      the clinically relevant substrates of SAMHD1, we demonstrate that THP-1
      CRISPR/Cas9 cells lacking a functional SAMHD1 gene showed increased sensitivity
      to the antimetabolites nelarabine, fludarabine, decitabine, vidarabine,
      clofarabine, and trifluridine. Within this Extra View, we discuss and build upon
      both these and our previously reported findings, and propose SAMHD1 is likely
      active against a variety of nucleoside analog antimetabolites present in anti
      cancer chemotherapies. Thus, SAMHD1 may constitute a promising target to improve
      a wide range of therapies for both hematological and non-haematological
      malignancies.

PMID- 28436710
TI  - Ischemic Ulcer Pain Is Both Nociceptive and Neuropathic Pain Based on a
      Discriminant Function Analysis Using the McGill Pain Questionnaire.
AB  - The McGill Pain Questionnaire (MPQ) is composed of 78 words reflecting the
      mechanisms underlying chronic pain conditions. Ischemic ulcer pain is generally
      regarded as a nociceptive and inflammatory pain condition. However, it is
      sometimes refractory to nonsteroidal anti-inflammatory drug (NSAID) and opioid
      treatment. We categorized ischemic pain into nociceptive/inflammatory pain (NocP)
      or neuropathic pain (NeP), on the basis of patients' descriptions of their pain
      using the MPQ. We investigated pain characteristics of 365 patients with NeP and
      124 with NocP using the 78 words of the MPQ. We thereby developed a discriminant
      function, which efficiently discriminates descriptions of NocP from those of NeP.
      We applied this function to 18 ischemic pain patients (before and after
      peripheral revascularization) and categorized their pain as either NocP or NeP.
      The discriminant probability of the function was 72.8% (P <.05), suggesting
      relatively accurate discrimination of NocP from NeP. Among the 78 words, only
      "annoying" was not utilized for the function. On the basis of this function, 9 of
      the 18 ischemic pain patients' complaints were classified as NeP. Ten patients
      received revascularization and after revascularization, 7 of 10 patients'
      complaints were still NeP. Our results suggest that ischemic ulcer pain should be
      regarded as a mixed pain condition composed of both NocP and NeP and that it
      might be treated with medications for NeP (e.g., pregabalin, duloxetine) in
      combination with NSAIDs and opioids.

PMID- 28436711
TI  - MiR-33b-5p sensitizes gastric cancer cells to chemotherapy drugs via inhibiting
      HMGA2 expression.
AB  - MicroRNAs (miRNAs) are internal, non-coding, and ~22 nt small RNAs that display
      cell- and tissue-specific expression. They play important regulatory roles in
      cell proliferation and chemo-sensitivity. This study focused on tumor-suppressive
      miR-33b-5p expression as well as its role in gastric cancer. MiR-33b-5p was found
      low expression in gastric cancer cell lines. Functionally, western blots and the
      luciferase reporter assay were used to confirm that HMGA2 was the potential
      target of miR-33b-5p. Next, we used CCK-8 kits to analyze the effect of miR-33b
      5p combined chemotherapy drugs on cell inhibition rate, and flow cytometry to
      analyze cells apoptosis. Colony formation ability was determined by plating at
      500 cells per well into six-well plates and culturing for 15 d. The results
      showed that upregulation of miR-33b-5p decreased expression of HMGA2 and
      inhibited gastric cancer cell growth as well as sensitized gastric cancer cells
      to chemotherapy drugs. MiR-33b-5p overexpression hindered luciferase activity of
      HMGA2,3'-untranslated region-based reporter construct in 293 T cells. These data
      demonstrate that miR-33b-5p may be a potential therapeutic target for gastric
      cancer and function as tumor-suppressive miRNA through targeting HMGA2 in gastric
      cancer.

PMID- 28436712
TI  - Disposition and metabolism of [14C]-galunisertib, a TGF-betaRI kinase/ALK5
      inhibitor, following oral administration in healthy subjects and mechanistic
      prediction of the effect of itraconazole on galunisertib pharmacokinetics.
AB  - 1. The disposition and metabolism of galunisertib (LY2157299 monohydrate, a TGF
      betaRI Kinase/ALK5 Inhibitor) was characterized following a single oral dose of
      150 mg of [14C]-galunisertib (100 uCi) to six healthy human subjects. 2. The
      galunisertib plasma half-life was 8.6 h, while the 14C half-life was 10.0 h.
      Galunisertib was abundant in circulation (40.3% of the 14C AUC024 h), with 7
      additional metabolites detected in plasma. Two metabolites LSN3199597 (M5, mono
      oxidation), and M4 (glucuronide of M3) were the most abundant circulating
      metabolites (10.7 and 9.0% of the 14C AUC024 h respectively). The pharmacological
      activity of LSN3199597 was tested and found to be significantly less potent than
      galunisertib. 3. The dose was recovered in feces (64.5%) and in urine (36.8%).
      Galunisertib was cleared primarily by metabolism, based on low recovery of parent
      in excreta (13.0% of dose). Due to the slow in vitro metabolism of galunisertib
      in suspended hepatocytes, a long term hepatocyte system was used to model the
      human excretion profile. 4. Expressed cytochromes P450 and hepatocytes indicated
      clearance was primarily CYP3A4-mediated. Mechanistic static modeling that
      incorporated small non-CYP-mediated metabolic clearance and renal clearance
      components predicted an AUC ratio of 4.7 for the effect of itraconazole, a strong
      CYP3A4 inhibitor, on galunisertib.

PMID- 28436713
TI  - Modified dextran, heparin-based triggered release microspheres for cardiovascular
      delivery of therapeutic drugs using protamine as a stimulus.
AB  - In this study, we describe the synthesis of an amine-modified acetalated dextran
      polymer, which is combined with heparin (HP) as the basis for a novel controlled
      release system. Dextran-amine (DEXAM) conjugates, synthesised using reductive
      amination, were incorporated into DEXAM/HP microspheres. HP binds to positively
      charged ammonium ions of the DEXAM conjugates, contributing to the structural
      integrity of the microspheres. Crystal violet (CV) was encapsulated inside
      DEXAM/HP microspheres as a model drug to test the system. Protamine with a high
      affinity for HP functioned as a trigger to release CV. DEXAM/HP microspheres were
      characterised by particle size, encapsulation efficiency, scanning electron
      microscope images, and in vitro release profile. Release of CV from microspheres
      varied with primary amine content of DEXAM conjugates, amount of HP, and
      concentration of protamine added. The system is considered for controlled
      delivery of agents without the necessity of chemical modification.

PMID- 28436714
TI  - A hemorrhagic complication after Onyx embolization of a tentorial dural
      arteriovenous fistula: A caution about subdural extension with pial arterial
      supply.
AB  - We report a case of tentorial dural arteriovenous fistula (DAVF) with a severe
      intracranial hemorrhage occurring after Onyx embolization. A 40-year-old man
      presented with an asymptomatic tentorial DAVF on angiography. Transarterial
      embolization with Onyx was performed via the middle meningeal artery, and the
      cast filled the fistula itself and its proximal draining vein. Postoperative
      angiography confirmed complete occlusion of the DAVF. A computed tomography scan
      performed immediately after the procedure demonstrated an acute subdural hematoma
      with the temporal hemorrhage. Emergency craniotomy revealed continuous arterial
      bleeding from a viable glomus-like vascular structure around the proximal part of
      the embolized draining vein, fed by a pial artery arising from the posterior
      cerebral artery. Pathologic findings suggested diagnosis of vascular malformation
      extending into the subdural space. Tentorial DAVFs can extend to the subdural
      space along their drainage route, and may be involved in severe hemorrhagic
      complications of curative endovascular treatment using Onyx, particularly those
      with pial arterial supply.

PMID- 28436715
TI  - Controlled invasive mechanical ventilation strategies in obese patients
      undergoing surgery.
AB  - INTRODUCTION: The obesity prevalence is increasing in surgical population. As the
      number of obese surgical patients increases, so does the demand for mechanical
      ventilation. Nevertheless, ventilatory strategies in this population are
      challenging, since obesity results in pathophysiological changes in respiratory
      function. Areas covered: We reviewed the impact of obesity on respiratory system
      and the effects of controlled invasive mechanical ventilation strategies in obese
      patients undergoing surgery. To date, there is no consensus regarding the optimal
      invasive mechanical ventilation strategy for obese surgical patients, and no
      evidence that possible intraoperative beneficial effects on oxygenation and
      mechanics translate into better postoperative pulmonary function or improved
      outcomes. Expert commentary: Before determining the ideal intraoperative
      ventilation strategy, it is important to analyze the pathophysiology and
      comorbidities of each obese patient. Protective ventilation with low tidal
      volume, driving pressure, energy, and mechanical power should be employed during
      surgery; however, further studies are required to clarify the most effective
      ventilation strategies, such as the optimal positive end-expiratory pressure and
      whether recruitment maneuvers minimize lung injury. In this context, an ongoing
      trial of intraoperative ventilation in obese patients (PROBESE) should help
      determine the mechanical ventilation strategy that best improves clinical outcome
      in patients with body mass index>=35kg/m2.

PMID- 28436716
TI  - Skin score correlates with global DNA methylation and GSTO1 A140D polymorphism in
      arsenic-affected population of Eastern India.
AB  - Arsenic is a potent environmental toxicant causing serious public health concerns
      in India, Bangladesh and other parts of the world. Gene- and promoter-specific
      hypermethylation has been reported in different arsenic-exposed cell lines,
      whereas whole genome DNA methylation study suggested genomic hypo- and
      hypermethylation after arsenic exposure in in vitro and in vivo studies. Along
      with other characteristic biomarkers, arsenic toxicity leads to typical skin
      lesions. The present study demonstrates significant correlation between
      severities of skin manifestations with their whole genome DNA methylation status
      as well as with a particular polymorphism (Ala 140 Asp) status in arsenic
      metabolizing enzyme Glutathione S-transferase Omega-1 (GSTO1) in arsenic-exposed
      population of the district of Nadia, West Bengal, India.

PMID- 28436717
TI  - Preparing Nursing Students for Mental Health Care: The Impact of a Recovery
      oriented Clinical Placement.
AB  - The provision of mental health care has recently focused on the concept of
      recovery-oriented care. Clinical placements are important for imparting recovery
      oriented knowledge and skills to students. However, it has been determined that
      not all clinical placements are beneficial for future nursing professionals. The
      aim of this study was to examine what elements of professional learning were
      facilitated by engagement in a recovery- and recreation-based clinical placement
      for pre-registration nursing students called Recovery Camp. Qualitative data were
      collected through individual interviews and reflective journals of pre
      registration nurses. Findings from this study indicate that Recovery Camp
      enhanced students' understanding of stigma, developed their professional
      knowledge and applied skills, and helped them gain insight into the role a
      consumer plays in his/her own recovery journey. Placements that allow pre
      registration nurses the opportunity to authentically engage with people with a
      lived experience of mental illness may assist in the effective development of
      future professionals in meeting their diverse needs.

PMID- 28436718
TI  - Design of a novel curcumin-soybean phosphatidylcholine complex-based targeted
      drug delivery systems.
AB  - Recently, the global trend in the field of nanomedicine has been toward the
      design of combination of nature active constituents and phospholipid (PC) to form
      a therapeutic drug-phospholipid complex. As a particular amphiphilic molecular
      complex, it can be a unique bridge of traditional dosage-form and novel drug
      delivery system. In thisarticle, on the basis of drug-phospholipid complex
      technique and self-assembly technique, we chose a pharmacologically safe and low
      toxic drug curcumin (CUR) to increase drug-loading ability, achieve
      controlled/sustained drug release and improve anticancer activity. A novel CUR
      soybean phosphatidylcholine (SPC) complex and CUR-SPC complex self-assembled
      nanoparticles (CUR-SPC NPs) were prepared by a co-solvent method and a
      nanoprecipitation method. DSPE-PEG-FA was further functionalized on the surface
      of PEG-CUR-SPC NPs (designed as FA-PEG-CUR-SPC NPs) to specifically increase
      cellular uptake and targetability. The FA-PEG-CUR-SPC NPs showed a spherical
      shape, a mean diameter of about 180 nm, an excellent physiological stability and
      pH-triggered drug release. The drug entrapment efficiency and drug-loading
      content was up to 92.5 and 16.3%, respectively. In vitro cellular uptake and
      cytotoxicity studies demonstrated that FA-PEG-CUR-SPC NPs and CUR-SPC NPs
      presented significantly stronger cellular uptake efficacy and anticancer activity
      against HeLa cells and Caco-2 cells compared to free CUR, CUR-SPC NPs and PEG-CUR
      SPC NPs. More importantly, FA-PEG-CUR-SPC NPs showed the prolonged systemic
      circulation lifetime and enhanced tumor accumulation compared with free CUR and
      PEG-CUR-SPC NPs. These results suggest that the FA targeted PEGylated CUR-SPC
      complex self-assembled NPs might be a promising candidate in cancer therapy.

PMID- 28436719
TI  - Gambling frequency and symptoms of attention-deficit hyperactivity disorder in
      relation to problem gambling among Swedish adolescents: a population-based study.
AB  - AIM: To investigate the associations between gambling frequency, attention
      deficit hyperactivity disorder (ADHD) symptoms, and problem gambling among
      adolescent boys and girls. One hypothesis was that adolescents with increased
      ADHD symptoms have a higher frequency of gambling compared to adolescents with
      fewer ADHD symptoms. METHOD: A population-based sample of adolescents (aged 15-18
      years) completed a questionnaire on demographics, gambling habits, ADHD symptoms,
      and problematic gambling; 1412 adolescents (from 4440 sampled) with gambling
      experience were included in the final sample. RESULTS: A zero-inflated negative
      binomial regression analysis revealed that increased ADHD symptoms, higher
      gambling frequency, and higher age were associated with lower odds for being non
      susceptible to gambling problems. Moreover, gambling frequency interacted with
      ADHD symptoms in predicting probability of being non-susceptible to gambling
      problems. However, when analysing those already susceptible to problem gambling,
      ADHD symptoms did not modify the effect of gambling frequency on the expected
      magnitude of gambling problems. In susceptible individuals, problem gambling
      increased with both increased ADHD symptoms and increased gambling frequency, but
      the level of problems due to gambling frequency did not change depending on the
      ADHD symptom level. There was an interaction effect between sex and gambling
      frequency in relation to gambling problems. CONCLUSIONS: Adolescents with ADHD
      symptoms seem to be more sensitive to gambling, in terms of being susceptible to
      developing gambling problems. However, once susceptible, adolescents with ADHD
      symptoms are affected by gambling frequency similarly to other susceptible
      participants.

PMID- 28436721
TI  - CROS editorial comment: Cardiac rehabilitation effectiveness in the 'new era':
      Any doubts after an acute coronary event?

PMID- 28436720
TI  - Efficacy and safety of statins and exercise combination therapy compared to
      statin monotherapy in patients with dyslipidaemia: A systematic review and meta
      analysis.
AB  - Background Statin treatment in association with physical exercise can
      substantially reduce mortality in dyslipidaemic individuals. However, the
      available data to compare the efficacy and safety of statins and exercise
      combination therapy with statin monotherapy are limited. Design Systematic review
      and meta-analysis. Methods We systematically searched PubMed, Embase and the
      Cochrane Library from database inception until December 2016. We included
      randomised and non-randomised studies that compared the efficacy and safety of
      statins and exercise combination therapy with statin monotherapy in patients with
      dyslipidaemia. Standardised mean differences were calculated and pooled by means
      of fixed effects models. The risk of bias and heterogeneity among trials was also
      assessed. Seven articles were assessed in terms of the efficacy of therapy and 13
      from the viewpoint of therapeutic safety. Results In terms of efficacy, statins
      and exercise combination decreased the incidence of diabetes mellitus, improved
      insulin sensitivity and inflammation, but caused no change in lipid profile
      compared to statins alone. In terms of safety, statins and exercise combination
      increased peak oxygen uptake (standardised mean difference 1.01, 95% confidence
      interval 0.46 to 1.57) compared to statins alone. In contrast to statin-induced
      myopathy, chronic exercise training prior to statin treatment could counteract
      statin-induced adverse effects in skeletal muscle. Conclusion Statins and
      exercise combination therapy is more effective than statin monotherapy in terms
      of insulin sensitivity, inflammation and exercise capacity. The small number of
      studies warrants the need for more randomised controlled trials evaluating the
      efficacy and safety of combination therapy.

PMID- 28436722
TI  - Exercise training improves characteristics of exercise oscillatory ventilation in
      chronic heart failure.
AB  - Background Exercise oscillatory ventilation in chronic heart failure has been
      suggested as a factor related to adverse cardiac events, aggravated prognosis and
      higher mortality. Exercise training is well known to affect exercise capacity and
      mechanisms of pathophysiology beneficially in chronic heart failure. Little is
      known, however, about the exercise training effects on characteristics of
      exercise oscillatory ventilation in chronic heart failure patients. Design and
      methods Twenty (out of 38) stable chronic heart failure patients exhibited
      exercise oscillatory ventilation (age 54 +/- 11 years, peak oxygen uptake 15.0 +/
      5.0 ml/kg per minute). Patients attended 36 sessions of high intensity interval
      exercise. All patients underwent cardiopulmonary exercise testing before and
      after the programme. Assessment of exercise oscillatory ventilation was based on
      the amplitude of cyclic fluctuations in breathing during rest and exercise. All
      values are mean +/- SD. Results Exercise training reduced ( P < 0.05) the
      percentage of exercise oscillatory ventilation duration (79.0 +/- 13.0 to 50.0 +/
      25.0%), while average amplitude (5.2 +/- 2.0 to 4.9 +/- 1.6 L/minute) and length
      (44.0 +/- 10.9 to 41.0 +/- 6.7 seconds) did not change ( P > 0.05). Exercise
      oscillatory ventilation patients also increased exercise capacity ( P < 0.05).
      Conclusions A rehabilitation programme based on high intensity interval training
      improved exercise oscillatory ventilation observed in chronic heart failure
      patients, as well as cardiopulmonary efficiency and functional capacity.

PMID- 28436723
TI  - Asymptomatic peripheral artery disease can limit maximal exercise capacity in
      chronic obstructive pulmonary disease patients regardless of airflow obstruction
      and lung hyperinflation.
AB  - Background Silent/asymptomatic peripheral artery disease may occur in patients
      with chronic obstructive pulmonary disease, but it is poorly investigated. The
      primary aim of this study was to evaluate in chronic obstructive pulmonary
      disease patients the impact of asymptomatic/silent peripheral artery disease on
      maximal exercise capacity; the secondary aim was to search for predictors of
      peripheral artery disease. Methods We prospectively enrolled chronic obstructive
      pulmonary disease outpatients. Data on anthropometric characteristics, lung
      function, cardiopulmonary exercise test and ankle-brachial index were recorded.
      The cut-off of ankle-brachial index used to define patients with peripheral
      artery disease was <=0.90. Results We studied 47 patients and found 24 patients
      (51%) who showed peripheral artery disease. As compared to patients without
      peripheral artery disease, patients with peripheral artery disease had lower
      values of peak oxygen uptake, peak workload, energy expenditure (metabolic
      equivalents) and heart rate recovery, but showed the same degree of airflow
      obstruction and static and dynamic hyperinflation. In a multivariate linear
      regression model performed to identify variables predicting metabolic
      equivalents, ankle-brachial index (beta 2.59; 95% confidence interval 0.51-4.67;
      p = 0.016) was an independent variable. In the search for predictors of
      peripheral artery disease, heart rate recovery (odds ratio 8.80; 95% confidence
      interval 1.30-59.35; p = 0.026) increased the risk of peripheral artery disease,
      whereas metabolic equivalents (odds ratio 0.50; 95% confidence interval 0.26
      0.94, p = 0.033) and inhaled corticosteroids+long-acting beta2 agonists (odds
      ratio 0.13; 95% confidence interval 0.02-0.83; p = 0.030) reduced this risk.
      Conclusions In chronic obstructive pulmonary disease outpatients,
      asymptomatic/silent peripheral artery disease affects the maximal exercise
      capacity regardless of airflow obstruction and lung hyperinflation. A delay of
      heart rate recovery increase the risk of peripheral artery disease, whereas high
      values of metabolic equivalents and the use of inhaled corticosteroids+long
      acting beta2 agonists reduces this risk.

PMID- 28436725
TI  - The impact of medication adherence on clinical outcomes of coronary artery
      disease: A meta-analysis.
AB  - Background Long-term use of evidence-based medications is recommended by
      international guidelines for the management of stable coronary artery disease,
      however, non-adherence to medications is common. This meta-analysis aims to
      systematically evaluate the impact of medication adherence on clinical outcomes
      in patients with stable coronary artery disease. Methods Articles from January
      1960-December 2015 were retrieved from the MEDLINE and EMBASE databases without
      any language restriction. A meta-analysis was performed to investigate the risk
      ratios of all-cause mortality, cardiovascular mortality, and myocardial
      infarction/hospitalization between groups with good medication adherence and poor
      medication adherence. Studies were independently reviewed by two investigators.
      Data from eligible studies were extracted, and the meta-analysis was performed
      using R Version 3.1.0 software. Results A total of 10 studies were included in
      the analysis, with a total of 106,002 coronary artery disease patients. The
      results showed that good adherence to evidence-based medication regimens,
      including beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin
      receptor blockers, antiplatelet drugs, and statins, was related to a lower risk
      of all-cause mortality(risk ratio 0.56; 95% confidence interval: 0.45-0.69),
      cardiovascular mortality(risk ratio 0.66; 95% confidence interval: 0.51-0.87),
      and cardiovascular hospitalization/myocardial infarction(risk ratio 0.61; 95%
      confidence interval: 0.45-0.82). Conclusions This meta-analysis confirms the
      significant impact of good medication adherence on clinical outcomes in patients
      with stable coronary artery disease. More strategy and planning are needed to
      improve medication adherence.

PMID- 28436724
TI  - Circulating proprotein convertase subtilisin-kexin type 9, all-cause mortality,
      and cardiovascular mortality: The Ludwigshafen Risk and Cardiovascular Health
      study.
AB  - Background It is unclear whether proprotein convertase subtilisin-kexin type 9
      (PCSK9) concentrations may be useful for cardiovascular risk stratification.
      Design The LUdwigshafen RIsk and Cardiovascular health (LURIC) study is a
      prospective observational registry of patients who were referred for coronary
      angiography. Methods Circulating PCSK9 was measured in 2139 participants of the
      LURIC study. There was a follow-up for all-cause and cardiovascular mortality
      with a median (interquartile range) duration of 10.1 (8.1-10.8) years. Results
      The mean (standard deviation) age of the participants (1470 males and 669
      females) was 62.6 (10.8) years, body mass index 27.3 (4.0) kg/m2, and low density
      lipoprotein cholesterol 114 (33) mg/dl. The mean (standard deviation) PCSK9
      concentration was 220 (82) ng/ml. Of the participants, 1035 (48.4%) were on
      statins. Use of statins was associated with significantly lower low density
      lipoprotein cholesterol (106 vs 121 mg/dl, p < 0.001) but significantly higher
      circulating PCSK9 (244 vs 197 ng/ml, p < 0.001). A total of 674 (31.5%) study
      participants died from any cause and 431 (20.1%) from cardiovascular diseases. In
      the entire cohort, the third vs first tertile of PCSK9 was not associated with
      the risk of death from any cause (hazard ratio = 1.09, p = 0.367) and from
      cardiovascular diseases (hazard ratio = 1.09, p = 0.476). In participants without
      statins, the third vs first PCSK9 tertile was modestly associated with increased
      all cause mortality (hazard ratio = 1.34, p = 0.029) but not with cardiovascular
      mortality (hazard ratio = 1.25, p = 0.194). Conclusions Circulating PCSK9 may be
      upregulated by statin use and does not appear to be useful for cardiovascular
      risk stratification.

PMID- 28436726
TI  - Impact of physical activity on the association of overweight and obesity with
      cardiovascular disease: The Rotterdam Study.
AB  - Background Being overweight or obese is associated with an increased risk of
      cardiovascular disease (CVD). Physical activity might reduce the risk associated
      with overweight and obesity. We examined the association between overweight and
      obesity and CVD risk as a function of physical activity levels in a middle-aged
      and elderly population. Design The study was a prospective cohort study. Methods
      The study included 5344 participants aged 55 years or older from the population
      based Rotterdam Study. Participants were classified as having high or low
      physical activity based on the median of the population. Normal weight (18.5-24.9
      kg/m2), overweight (25.0-29.9 kg/m2) and obese participants (>=30 kg/m2) were
      categorized as having high or low physical activity to form six categories. We
      assessed the association of the six categories with CVD risk using Cox
      proportional hazard models adjusted for confounders. High physical activity and
      normal weight was used as the reference group. Results During 15 years of follow
      up (median 10.3 years, interquartile range 8.2-11.7 years), 866 (16.2%)
      participants experienced a CVD event. Overweight and obese participants with low
      physical activity had a higher CVD risk than normal weight participants with high
      physical activity. The HRs and 95% confidence intervals (CIs) were 1.33 (1.07
      1.66) and 1.35 (1.04-1.75), respectively. Overweight and obese participants with
      high physical activity did not show a higher CVD risk (HRs (95%CIs) 1.03 (0.82
      1.29) and 1.12 (0.83-1.52), respectively). Conclusions Our findings suggest that
      the beneficial impact of physical activity on CVD might outweigh the negative
      impact of body mass index among middle-aged and elderly people. This emphasizes
      the importance of physical activity for everyone across all body mass index
      strata, while highlighting the risk associated with inactivity even among normal
      weight people.

PMID- 28436727
TI  - Impact of switching from different treatment regimens to a fixed-dose combination
      pill (polypill) in patients with cardiovascular disease or similarly high risk.
AB  - Aims Cardiovascular fixed-dose combination pills, or polypills, may help address
      the widespread lack of access and adherence to proven medicines. Initiation of
      polypill-based care typically entails switching from current separately taken
      medications. Given the heterogeneity in usual care, there is interest in the
      impact of polypill treatment across different patterns of prior medication
      regimen. Methods A total of 2004 participants with established cardiovascular
      disease or estimated 5-year cardiovascular risk of over 15% were randomised to
      polypill-based treatment (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and
      either atenolol 50 mg or hydrochlorothiazide 12.5 mg) or usual care. Baseline
      medications were classified by potency relative to polypill components. Estimated
      cardiovascular risk reduction was calculated by combining risk factor changes
      with results seen in meta-analyses of previous randomised trials. Results For
      cholesterol reduction conferred by polypills, there was a dose response across
      baseline statin groups, with mean low-density lipoprotein (LDL)-cholesterol
      differences of 0.37, 0.22, 0.14 and 0.07 mmol/L among patients taking no statin,
      less potent, equipotent and more potent statin at baseline, respectively.
      Similarly there were differences in mean systolic BP of 5.4, 6.2, 3.3 and 1.8
      mmHg among patients taking 0, 1, 2 or 3 BP-lowering agents. Among patients taking
      more potent statins at baseline, there was no significant difference in LDL
      cholesterol but there were benefits for BP and aspirin adherence. Similar results
      were seen among patients taking 3 BP-lowering agents at baseline. Switching to a
      polypill-based strategy resulted in estimated cardiovascular relative risk
      reductions across a wide range of usual care patterns of antiplatelet, statin and
      BP-lowering therapy prescribing. Conclusion Adherence benefits from switching to
      a polypill resulted in risk factor changes that were at least as good as usual
      care across a wide variety of treatment patterns, including equally potent or
      more potent regimens. The benefits of switching to polypill-based care were
      greatest among those stepped up from partial treatment or less potent treatment.

PMID- 28436728
TI  - Trends in the risk of early and late-onset heart failure as an adverse outcome of
      acute myocardial infarction: A Cardiovascular Disease in Norway project.
AB  - Aims Heart failure is a serious complication of acute myocardial infarction,
      leading to a poor prognosis. We explored trends in the risk of heart failure
      among patients hospitalised with an incident acute myocardial infarction in
      Norway during 2001-2009. Methods and results A total of 69,372 patients were
      followed for an episode of heart failure occurring either during (early-onset
      heart failure) or within one year of discharge from the incident acute myocardial
      infarction hospitalisation (late-onset heart failure). Logistic regression and
      competing risk regression models were used to explore trends in early and late
      onset heart failure respectively. Overall, 17.1% of patients had early-onset
      heart failure. The odds of heart failure increased by 2.3% per year (odds ratio =
      1.023; 95% confidence interval: 1.015-1.031), influenced by an increase of 5.9%
      per year among younger (25-69 years) patients while no statistically significant
      changes occurred among older (70-84 years) patients. Among 47,673 patients
      discharged alive, without early-onset heart failure, 5.4% experienced late-onset
      heart failure. The risk of heart failure declined by 6.3% per year (subhazard
      ratio = 0.937; 95% confidence interval: 0.921-0.954). The decline was
      statistically significant in both age groups (6.8% per year and 5.9% per year
      respectively). Overall, the risk of heart failure occurring at any time during
      the follow up did not change significantly. However, it increased by 3.3% per
      year in younger patients and declined by 1.5% per year in older patients.
      Conclusions Heart failure occurring during acute myocardial infarction
      hospitalisation accounts for the majority of heart failure cases and is
      characterised by unfavourable trends, while heart failure rates following acute
      myocardial infarction discharge declined over the study period.

PMID- 28436729
TI  - Re: History of erectile dysfunction as a predictor of poor physical performance
      after an acute myocardial infarction.

PMID- 28436730
TI  - A new approach to managing work-related road traffic injury: The development of a
      health investment framework.
AB  - OBJECTIVE: Statistics indicate that employees commuting or traveling as part of
      their work are overrepresented in workplace injury and death. Despite this, many
      organizations are unaware of the factors within their organizations that are
      likely to influence potential reductions in work-related road traffic injury.
      METHODS: This article presents a multilevel conceptual framework that identifies
      health investment as the central feature in reducing work-related road traffic
      injury. Within this framework, we explore factors operating at the individual
      driver, workgroup supervisor, and organizational senior management levels that
      create a mutually reinforcing system of safety. RESULTS: The health investment
      framework identifies key factors at the senior manager, supervisor, and driver
      levels to cultivating a safe working environment. These factors are high
      performance workplace systems, leader-member exchange and autonomy, trust and
      empowerment, respectively. The framework demonstrates the important interactions
      between these factors and how they create a self-sustaining organizational safety
      system. CONCLUSIONS: The framework aims to provide insight into the future
      development of interventions that are strategically aligned with the organization
      and target elements that facilitate and enhance driver safety and ultimately
      reduce work-related road traffic injury and death.

PMID- 28436731
TI  - Fatal and serious collisions involving pedal cyclists and trucks in London
      between 2007 and 2011.
AB  - OBJECTIVE: Increased numbers of people riding pedal cycles have led to a greater
      focus on pedal cycle safety. The aim of this article is to explore factors that
      are associated with fatal and a small number of serious-injury pedal cyclist
      crashes involving trucks that occurred in London between 2007 and 2011. METHODS:
      Data were collected from police collision files for 53 crashes, 27 of which
      involved a truck (>=3.5 tonnes) and a pedal cycle. A systematic case review
      approach was used to identify the infrastructure, vehicle road user, and
      management factors that contributed to these crashes and injuries and how these
      factors interacted. RESULTS: Trucks turning left conflicting with pedal cyclists
      traveling straight ahead was a common crash scenario. Key contributory factors
      identified included the pedal cyclists not being visible to the truck drivers,
      road narrowing, and inappropriate positioning of pedal cyclists. CONCLUSIONS:
      Crashes involving trucks and pedal cyclists are complex events that are caused by
      multiple interacting factors; therefore, multiple measures are required to
      prevent them from occurring.

PMID- 28436732
TI  - Administrative license suspension: Does length of suspension matter?
AB  - OBJECTIVE: Administrative license revocation (ALR) laws, which provide that the
      license of a driver with a blood alcohol concentration at or over the illegal
      limit is subject to an immediate suspension by the state department of motor
      vehicles, are an example of a traffic law in which the sanction rapidly follows
      the offense. The power of ALR laws has been attributed to how swiftly the
      sanction is applied, but does the length of suspension matter? Our objectives
      were to (a) determine the relationship of the ALR suspension length to the
      prevalence of drinking drivers relative to sober drivers in fatal crashes and (b)
      estimate the extent to which the relationship is associated to the general
      deterrent effect compared to the specific deterrent effect of the law. METHODS:
      Data comparing the impact of ALR law implementation and ALR law suspension
      periods were analyzed using structural equation modeling techniques on the ratio
      of drinking drivers to nondrinking drivers in fatal crashes from the Fatality
      Analysis Reporting System (FARS). RESULTS: States with an ALR law with a short
      suspension period (1-30 days) had a significantly lower drinking driver ratio
      than states with no ALR law. States with a suspension period of 91-180 days had
      significantly lower ratios than states with shorter suspension periods, while the
      three states with suspension lengths of 181 days or longer had significantly
      lower ratios than states with shorter suspension periods. DISCUSSION: The
      implementation of any ALR law was associated with a 13.1% decrease in the
      drinking/nondrinking driver fatal crash ratio but only a 1.8% decrease in the
      intoxicated/nonintoxicated fatal crash ratio. The ALR laws and suspension lengths
      had a significant general deterrent effect, but no specific deterrent effect.
      PRACTICAL IMPLICATIONS: States might want to keep (or adopt) ALR laws for their
      general deterrent effects and pursue alternatives for specific deterrent effects.
      States with short ALR suspension periods should consider lengthening them to 91
      days or longer.

PMID- 28436733
TI  - Social and hospital costs of patients admitted to a university hospital in Brazil
      due to motorcycle crashes.
AB  - OBJECTIVE: This study aimed to investigate the social and hospital costs of
      patients treated at a public hospital who were motorcycle crash victims. METHOD:
      This prospective study was on 68 motorcycle riders (drivers or passengers), who
      were followed up from hospital admission to 6 months after the crash. A
      questionnaire covering quantitative and qualitative questions was administered.
      RESULTS: Motorcycle crash victims were responsible for 12% of the institution's
      hospital admissions; 54.4% were young (18-28 years of age); 92.6% were the
      drivers; 91.2% were male; and 50% used their motorcycles as daily means of
      transportation. Six months afterward, 94.1% needed help from someone; 83.8% had
      changed their family dynamics; and 73.5% had not returned to their professional
      activities. Among the injuries, 94.7% had some type of fracture, of which 53.5%
      were exposed fractures; 35.3% presented temporary sequelae; and 32.4% presented
      permanent sequelae. They used the surgical center 2.53 times on average, with a
      mean hospital stay of 18 days. The per capita hospital cost of these victims'
      treatment was US$17,481.50. CONCLUSION: The social and hospital costs were high,
      relative to the characteristics of a public institution. Temporary or permanent
      disability caused changes to family dynamics, as shown by the high numbers of
      patients who were still away from their professional activities more than 6
      months afterward.

PMID- 28436734
TI  - Effects of speed-control measures on the safety of unsignalized midblock street
      crossings in China.
AB  - OBJECTIVE: The primary objective of this study was to evaluate the effects of
      different speed-control measures on the safety of unsignalized midblock street
      crossings. METHODS: In China, it is quite difficult to obtain traffic crash and
      conflict data for pedestrians using such crossings, mainly due to the lack of
      traffic data management and organizational issues. In light of this, the proposed
      method did not rely on such data, but considered vehicle speed, which is a
      leading contributing factor of pedestrian safety at mid blocks. To evaluate the
      speed reduction effects at different locations, the research team utilized the
      following methods in this study: (1) testing speed differences-on the basis of
      the collected data, statistical analysis is conducted to test the speed
      differences between upstream and crosswalk, upstream and downstream, and
      downstream and crosswalk; and (2) mean distribution deviation-this value is
      calculated by taking the difference in cumulative speed distributions for the two
      different samples just mentioned. In order to better understand the variation of
      speed reduction effects at different distances from speed-control facilities,
      data were collected from six types of speed-control measures with a visual range
      of 60 m. RESULTS: The results showed that speed humps, transverse rumble strips,
      and speed bumps were effective in reducing vehicle speeds. Among them speed humps
      performed the best, with reductions of 21.1% and 20.0% from upstream location
      (25.01 km/h) and downstream location (24.66 km/h) to pedestrian crosswalk (19.73
      km/h), respectively. By contrast, the speed reduction effects were minimal for
      stop and yield signs, flashing yellow lights, and crossings without treatment.
      CONCLUSIONS: Consequently, in order to reduce vehicle speeds and improve
      pedestrian safety at mid blocks, several speed-control measures such as speed
      humps, speed bumps, and transverse rumble strips are recommended to be deployed
      in the vicinity of pedestrian crosswalks.

PMID- 28436735
TI  - Risk and safety perception on urban and rural roads: Effects of environmental
      features, driver age and risk sensitivity.
AB  - OBJECTIVE: The ability to detect changing visual information is a vital component
      of safe driving. In addition to detecting changing visual information, drivers
      must also interpret its relevance to safety. Environmental changes considered to
      have high safety relevance will likely demand greater attention and more timely
      responses than those considered to have lower safety relevance. The aim of this
      study was to explore factors that are likely to influence perceptions of risk and
      safety regarding changing visual information in the driving environment. Factors
      explored were the environment in which the change occurs (i.e., urban vs. rural),
      the type of object that changes, and the driver's age, experience, and risk
      sensitivity. METHODS: Sixty-three licensed drivers aged 18-70 years completed a
      hazard rating task, which required them to rate the perceived hazardousness of
      changing specific elements within urban and rural driving environments. Three
      attributes of potential hazards were systematically manipulated: the environment
      (urban, rural); the type of object changed (road sign, car, motorcycle,
      pedestrian, traffic light, animal, tree); and its inherent safety risk (low risk,
      high risk). Inherent safety risk was manipulated by either varying the object's
      placement, on/near or away from the road, or altering an infrastructure element
      that would require a change to driver behavior. Participants also completed two
      driving-related risk perception tasks, rating their relative crash risk and
      perceived risk of aberrant driving behaviors. RESULTS: Driver age was not
      significantly associated with hazard ratings, but individual differences in
      perceived risk of aberrant driving behaviors predicted hazard ratings, suggesting
      that general driving-related risk sensitivity plays a strong role in safety
      perception. In both urban and rural scenes, there were significant associations
      between hazard ratings and inherent safety risk, with low-risk changes perceived
      as consistently less hazardous than high-risk impact changes; however, the effect
      was larger for urban environments. There were also effects of object type, with
      certain objects rated as consistently more safety relevant. In urban scenes,
      changes involving pedestrians were rated significantly more hazardous than all
      other objects, and in rural scenes, changes involving animals were rated as
      significantly more hazardous. Notably, hazard ratings were found to be higher in
      urban compared with rural driving environments, even when changes were matched
      between environments. CONCLUSION: This study demonstrates that drivers perceive
      rural roads as less risky than urban roads, even when similar scenarios occur in
      both environments. Age did not affect hazard ratings. Instead, the findings
      suggest that the assessment of risk posed by hazards is influenced more by
      individual differences in risk sensitivity. This highlights the need for driver
      education to account for appraisal of hazards' risk and relevance, in addition to
      hazard detection, when considering factors that promote road safety.

PMID- 28436736
TI  - Are you okay to drive? Commuting behavior and blood alcohol concentrations among
      restaurant diners.
AB  - OBJECTIVE: Drink driving is widely recognized as a major road safety problem. In
      Australia, health promotion messages encourage monitoring the number of standard
      drinks consumed prior to driving. This pilot research aimed to investigate
      commuting behavior and blood alcohol concentration (BAC) of diners, including
      intended drivers, at Sunshine Coast restaurants. METHODS: Five hundred and forty
      four diners (n = 260 males) consented to participate in a brief interview and to
      use a breathalyzer device to measure their BAC. RESULTS: Forty percent of
      participants advised they don't drink and drive (34% of males, 45% of females;
      67.25% of <17-20 years, 30.5% of 50-59 years), and of the remaining participants,
      75% advised they count the number of their drinks (69% of males, 84% of females;
      32% of <17-20 years, 82% of 50-59 years), while 10% of participants monitored
      their BAC by how they were feeling (12% of males, 6% of females). Thirty-seven
      percent of participants said it was easy/very easy to estimate their BAC (41% of
      males; 33% of females; 21% of <17-20 years, 43% of 50-59 years). The actual BAC
      was less than expected for 56% of participants, with one-third underestimating
      BAC and some intended drivers having an actual BAC in excess of the 0.05 limit.
      CONCLUSIONS: Given the proportion of diners who reported they count the number of
      drinks, or use feelings as a way to gauge BAC, coupled with the considerable
      proportion who underestimated their BAC, a safer public health message is to
      avoid driving if you intend to drink. In addition, targeted intervention for
      experienced drivers (and, arguably, drinkers) appears warranted, as every
      participant aged less than 21 years who stated he or she would drive home indeed
      had a zero BAC. Interestingly every female driver who stated she would be driving
      home also had a legal BAC, suggesting gender-specific intervention.

PMID- 28436737
TI  - Bicycle helmet effectiveness is not overstated.
AB  - OBJECTIVE: The objective of this study was to discuss the challenges in
      estimating bicycle helmet effectiveness from case-control studies of injured
      cyclists and to estimate helmet effectiveness from cases and available exposure
      data. METHODS: Data were extracted from studies of cyclists in Seattle; Victoria
      and New South Wales, Australia; and The Netherlands. Estimates of helmet use were
      used as exposure to compute relative risks for Seattle and Victorian data.
      Cycling distance data are routinely collected in The Netherlands; however, these
      data cannot be disaggregated by helmet use, which makes it unsuitable for
      estimating helmet effectiveness. Alternative controls were identified from larger
      cohorts for the Seattle and New South Wales cases. RESULTS: Estimates of helmet
      effectiveness were similar from odds ratios (ORs) using hospital controls or from
      relative risks (RRs) using helmet use estimates (Seattle: OR = 0.339, RR = 0.444;
      Victoria: OR = 0.500, RR = 0.353). Additionally, the odds ratios using hospital
      controls were similar when controls were taken from a larger cohort for head
      injury of any severity (Seattle: OR = 0.250, alt OR = 0.257; NSW: OR = 0.446, alt
      OR = 0.411) and for serious head injury (Seattle: OR = 0.135, alt OR = 0.139;
      NSW: OR = 0.335, alt OR = 0.308). Although relevant exposure data were
      unavailable for The Netherlands, the odds ratio for helmet effectiveness of those
      using racing, mountain, or hybrid bikes was similar to other estimates (OR =
      0.371). CONCLUSIONS: Despite potential weaknesses with case-control study
      designs, the best available evidence suggests that helmet use is an effective
      measure of reducing cycling head injury.

PMID- 28436738
TI  - Brainstem injury in motor vehicle crashes.
AB  - OBJECTIVE: This is a descriptive study of the frequency and risk for brainstem
      injury by crash type, belt use, and crash severity (delta-V). NASS-CDS electronic
      cases were reviewed to see whether the transition from vehicles without advanced
      airbags and seat belts and side airbags and curtains to vehicles with the safety
      technologies has influenced the risk for brainstem injury. METHODS: 1994-2013
      NASS-CDS was analyzed to determine the number of brainstem injuries in nonejected
      adults (15+ years old) in vehicle crashes. Crashes were grouped by front, side,
      rear, and rollover. The effect of belt use was investigated. Light vehicles were
      included with model year (MY) 1994+. Occupants with severe head injury
      (Abbreviated Injury Scale [AIS] 4+) and Maximum Abbreviated Injury Scale (MAIS)
      4+F injury were also determined. The risk for injury with standard errors was
      determined using the MAIS 0+F exposure by belt use and crash type. NASS-CDS
      electronic cases were studied with brainstem injury in 2001-2013 MY vehicles.
      RESULTS: NASS-CDS indicates there are 872 +/- 133 cases of brainstem injury per
      year. About 16.0% of AIS 4+ head injury involves the brainstem. For belted
      occupants, the highest risk for brainstem injury was in side impacts at 0.065 +/-
      0.010%. In contrast, the highest risk for brainstem injury was 0.310 +/- 0.291%
      in rear impacts and 0.310 +/- 0.170% in rollovers for unbelted occupants. The
      risk for brainstem injury increased with crash severity. The highest risk for
      brainstem injury was 3.54 +/- 1.45% in crashes with >72 km/h (>45 mph) delta-V.
      Exponential functions fit the change in risk with delta-V. Eighteen NASS-CDS
      electronic cases showed that brainstem injury occurred in very severe collisions
      where the occupant experienced multiple injuries from intrusion or impact on
      vehicle structures stiffened by deformation. CONCLUSIONS: The risk for brainstem
      injury in belted occupants has remained essentially constant over 20 years,
      whereas the risk for MAIS 4+F injury has declined 38.3%. The prevention of
      brainstem injuries must address the extreme speed of collisions and weight
      mismatches that overwhelm structures, seat belts, frontal airbags, side airbags,
      and curtains in modern vehicles.

PMID- 28436739
TI  - Prediabetes Exhibits Decreased Disposition Index Correlated with Deterioration of
      Glycemic Parameters in Nonobese Japanese Subjects: A Cross-Sectional Study from
      Medical Examination.
AB  - BACKGROUND: Prediabetes, defined as impaired fasting glucose (IFG) and impaired
      glucose tolerance (IGT), likely develops to type 2 diabetes mellitus (DM) and
      independently increases cardiovascular risk. We employed disposition index (DI),
      a new metabolic parameter indicating the pancreatic beta cell function adjusted
      for insulin resistance, and investigated whether it could be altered in Japanese
      population with prediabetes and associated with early glucose intolerance.
      METHODS: A total of 102 adults who underwent an oral glucose tolerance test at
      the medical screening were designated to normal glucose tolerance (NGT), IFG,
      IGT, and DM. We calculated insulinogenic index (IGI) and homeostasis model
      assessment (HOMA) of beta cell function (HOMA-beta) as insulin secretory
      function, HOMA-insulin resistance (HOMA-IR), and quantitative insulin sensitivity
      check index (QUICKI) as insulin resistance and DI, and assessed correlations
      between these indices and glycemic parameters. RESULTS: We observed graded
      increase of glycemic parameters in the order of NGT, IFG, IGT, and DM. HOMA-IR
      was significantly higher only in DM compared with NGT, although HOMA-beta, IGI,
      and QUICKI showed no significant differences among the groups. In contrast, DI
      was significantly lower in IFG, IGT, and DM compared with NGT. In correlation
      analysis, glycemic parameters related positively to HOMA-IR, but inversely to DI.
      Only two parameters, IGI and particularly DI, were significantly decreased in the
      subjects with 1-hr postload glucose >8.6 mmol/L previously proposed as a
      predictor of type 2 diabetes. CONCLUSIONS: Our results suggest that reduction of
      DI promptly reflects the alteration of early glucose intolerance in Japanese
      population presenting with prediabetes.

PMID- 28436740
TI  - Major Immunodominant Region of Hepatitis B Virus Core Antigen as a Delivery
      Vector to Improve the Immunogenicity of the Fusion Antigen ROP2-SAG1 Multiepitope
      from Toxoplasma gondii in Mice.
AB  - To prepare the dominant multiepitope fusion antigen ROP2-SAG1 (RSmultiepitope)
      from Toxoplasma gondii in a prokaryotic system, the major immunodominant region
      (MIR) of the human hepatitis B virus core antigen (HBcAg(MIR)) was used as a
      delivery vector. The gene encoding the RSmultiepitope was inserted into
      HBcAg(MIR), and rHBcAg(MIR)-RSmultiepitope was prepared, purified, and
      administered to BALB/c mice through intradermal injection. An indirect enzyme
      linked immunosorbent assay analysis based on a multiepitope peptide facilitated
      the specific differentiation of sera obtained from mice immunized with the
      rHBcAg(MIR)-RSmultiepitope protein, and high titers (greater than 1:6,400) of
      specific anti-RSmultiepitope antibodies were obtained. Immunized splenocytes
      demonstrated enhanced IFN-gamma production. Based on these results, the
      HBcAg(MIR) vector is easily applied in vitro for targeting the RSmultiepitope and
      efficiently presents this target epitope for the induction of significant humoral
      and cellular immune responses. This study offers a novel strategy for the design
      of a target epitope delivery system for a toxoplasmosis vaccine.

PMID- 28436741
TI  - Deep Learning at Chest Radiography: Automated Classification of Pulmonary
      Tuberculosis by Using Convolutional Neural Networks.
AB  - Purpose To evaluate the efficacy of deep convolutional neural networks (DCNNs)
      for detecting tuberculosis (TB) on chest radiographs. Materials and Methods Four
      deidentified HIPAA-compliant datasets were used in this study that were exempted
      from review by the institutional review board, which consisted of 1007
      posteroanterior chest radiographs. The datasets were split into training (68.0%),
      validation (17.1%), and test (14.9%). Two different DCNNs, AlexNet and GoogLeNet,
      were used to classify the images as having manifestations of pulmonary TB or as
      healthy. Both untrained and pretrained networks on ImageNet were used, and
      augmentation with multiple preprocessing techniques. Ensembles were performed on
      the best-performing algorithms. For cases where the classifiers were in
      disagreement, an independent board-certified cardiothoracic radiologist blindly
      interpreted the images to evaluate a potential radiologist-augmented workflow.
      Receiver operating characteristic curves and areas under the curve (AUCs) were
      used to assess model performance by using the DeLong method for statistical
      comparison of receiver operating characteristic curves. Results The best
      performing classifier had an AUC of 0.99, which was an ensemble of the AlexNet
      and GoogLeNet DCNNs. The AUCs of the pretrained models were greater than that of
      the untrained models (P < .001). Augmenting the dataset further increased
      accuracy (P values for AlexNet and GoogLeNet were .03 and .02, respectively). The
      DCNNs had disagreement in 13 of the 150 test cases, which were blindly reviewed
      by a cardiothoracic radiologist, who correctly interpreted all 13 cases (100%).
      This radiologist-augmented approach resulted in a sensitivity of 97.3% and
      specificity 100%. Conclusion Deep learning with DCNNs can accurately classify TB
      at chest radiography with an AUC of 0.99. A radiologist-augmented approach for
      cases where there was disagreement among the classifiers further improved
      accuracy. (c) RSNA, 2017.

PMID- 28436743
TI  - Ebola salience, death-thought accessibility, and worldview defense: A terror
      management theory perspective.
AB  - According to terror management theory, individuals defend their cultural beliefs
      following mortality salience. The current research examined whether naturally
      occurring instances of death (i.e., Ebola) correspond to results found in
      laboratory studies. The results of two experiments demonstrated that participants
      experienced a greater accessibility of death-related thoughts in response to an
      Ebola prime during a regional outbreak. Study 2 also showed that increased
      mortality awareness following an Ebola manipulation was associated with greater
      worldview defense (i.e., religious fundamentalism). Together, these results
      suggest that reminders of death in the form of a disease threat operate similarly
      to a mortality salience manipulation.

PMID- 28436744
TI  - Cognitive screening in substance users: Diagnostic accuracies of the Mini-Mental
      State Examination, Addenbrooke's Cognitive Examination-Revised, and Montreal
      Cognitive Assessment.
AB  - INTRODUCTION: Despite the considerable prevalence of cognitive impairment in
      substance-using populations, there has been little investigation of the utility
      of cognitive screening measures within this context. In the present study the
      accuracy of three cognitive screening measures in this population was examined
      the Mini-Mental State Examination (MMSE), the Addenbrooke's Cognitive Examination
      Revised (ACE-R), and the Montreal Cognitive Assessment (MoCA). METHOD: A sample
      of 30 treatment-seeking substance users and 20 healthy individuals living in the
      community were administered the screening measures and a neuropsychological
      battery (NPB). Agreement of classification of cognitive impairment by the
      screening measures and NPB was examined. RESULTS: Results indicated that the ACE
      R and MoCA had good discriminative ability in detection of cognitive impairment,
      with areas under the receiver-operating characteristic (ROC) curve of .85 (95%
      confidence interval, CI [.75. .94] and .84 (95% CI [.71, .93]) respectively. The
      MMSE had fair discriminative ability (.78, 95% CI [.65, .93]). The optimal cut
      score for the ACE-R was 93 (impairment = score of 92 or less), at which it
      correctly classified 89% of individuals as cognitively impaired or intact, while
      the optimal cut-score for the MoCA was <26 or <27 depending on preference for
      either specificity or sensitivity. The optimal cut-score for the MMSE was <29;
      however, this had low sensitivity despite good specificity. CONCLUSIONS: These
      findings suggest that the MoCA and ACE-R are both valid and time-efficient
      screening tools to detect cognitive impairment in the context of substance use.

PMID- 28436742
TI  - Training Pediatric Fellows in Palliative Care: A Pilot Comparison of Simulation
      Training and Didactic Education.
AB  - BACKGROUND: Pediatric fellows receive little palliative care (PC) education and
      have few opportunities to practice communication skills. OBJECTIVE: In this pilot
      study, we assessed (1) the relative effectiveness of simulation-based versus
      didactic education, (2) communication skill retention, and (3) effect on PC
      consultation rates. DESIGN: Thirty-five pediatric fellows in cardiology, critical
      care, hematology/oncology, and neonatology at two institutions enrolled: 17 in
      the intervention (simulation-based) group (single institution) and 18 in the
      control (didactic education) group (second institution). Intervention group
      participants participated in a two-day program over three months (three
      simulations and videotaped PC panel). Control group participants received written
      education designed to be similar in content and time. MEASUREMENTS: (1) Self
      assessment questionnaires were completed at baseline, post-intervention and three
      months; mean between-group differences for each outcome measure were assessed.
      (2) External reviewers rated simulation-group encounters on nine communication
      domains. Within-group changes over time were assessed. (3) The simulation-based
      site's PC consultations were compared in the six months pre- and post
      intervention. RESULTS: Compared to the control group, participants in the
      intervention group improved in self-efficacy (p = 0.003) and perceived adequacy
      of medical education (p < 0.001), but not knowledge (p = 0.20). Reviewers noted
      nonsustained improvement in four domains: relationship building (p = 0.01),
      opening discussion (p = 0.03), gathering information (p = 0.01), and
      communicating accurate information (p = 0.04). PC consultation rate increased
      64%, an improvement when normalized to average daily census (p = 0.04).
      CONCLUSIONS: This simulation-based curriculum is an effective method for
      improving PC comfort, education, and consults. More frequent practice is likely
      needed to lead to sustained improvements in communication competence.

PMID- 28436745
TI  - Does contact at work extend its influence beyond prejudice? Evidence from
      healthcare settings.
AB  - This article reports on two studies investigating the role of intergroup contact
      on the reduction of prejudice against migrants and on organizational and health
      outcomes. Study 1 enrolled 624 native healthcare professionals and showed that
      frequent and positive contact with non-native co-workers was associated with a
      decrease in the professionals' prejudice and an increase in the professionals'
      perception of team functioning. These effects were mediated by reduced in-group
      threat perception. Study 2 enrolled 201 native patients and showed that frequent
      and positive contact with non-native healthcare providers was associated with a
      decrease in patients' prejudice and an increase in patients' satisfaction for the
      care received. These effects were mediated by reduced in-group threat perception.
      These novel findings showed that frequent and positive contact with non-native
      individuals can improve health and organizational outcomes along with
      facilitating positive intergroup relations.

PMID- 28436746
TI  - Penetration Time Profiles for Two Class 3B Lasers in In Situ Human Achilles at
      Rest and Stretched.
AB  - BACKGROUND AND OBJECTIVE: The majority of studies investigating penetration of
      laser light are performed in vitro on skin flaps, with measures of immediate
      penetration depth and energy loss. The aim of this study was to investigate the
      penetration time profiles for two different lasers used in low-level laser
      therapy, during 150 sec of exposure both in stretched and relaxed human Achilles
      in situ. MATERIALS AND METHODS: Thirty-four Achilles tendons from 17 healthy
      volunteers were irradiated by an 810 nm, 200 mW, continuous- and a 904 nm, 60 mW,
      super-pulsed laser. Irradiation was performed with the Achilles tendons in
      relaxed and stretched condition. The energy penetrating skin-skin was measured
      every 30 sec using an optical power meter. RESULTS: The 810 nm laser penetration
      ability did not differ significantly in relaxed and stretched condition with
      0.17% [standard error of the mean (SEM) 0.02] of mean output power (MOP) and
      0.02% (SEM 0.004) of MOP, respectively. The 904 nm laser demonstrated a
      statistical significant (p < 0.05) and almost linear increasing penetration
      ability both in relaxed and stretched Achilles from 0.25% (SEM 0.03) to 0.38%
      (SEM 0.04) of MOP and from 0.05% (SEM 0.01) to 0.13% (SEM 0.01) of MOP,
      respectively. The penetrated ability differed between lasers and tissue
      conditions at all measure points (p < 0.05). CONCLUSIONS: The 904 nm laser
      penetrates relatively more energy than the 810 nm laser in in situ human
      Achilles. Moreover, penetration from the super-pulsed 904 nm laser increased
      during exposure time, whereas penetration from the 810 nm laser was constant. In
      addition, stretching the Achilles causes a higher energy attenuation by the
      tissue.

PMID- 28436747
TI  - Difructose anhydride III decreases body fat as a low-energy substitute or by
      decreasing energy intake in non-ovariectomized and ovariectomized female rats.
AB  - We evaluated the effects of difructose anhydride III (DFAIII) on body weights of
      ovariectomized rats, which are a good model for obesity by estrogen deficiency
      induced overeating. Female rats (10 weeks old) were subjected to ovariectomy or
      sham operation and then fed with or without a diet containing 3% or 6% DFAIII for
      33 days or pair-fed control diet during the same period. Rats fed DFAIII showed
      significantly decreased food intake, energy intake, body weight gain, body energy
      accumulation, and fat tissue weight than control group, regardless of
      ovariectomy. DFAIII may decrease body fat dependent of reduced food/energy
      intake. Compared with the respective pair feeding groups, rats fed DFAIII showed
      significantly decreased body energy and fat tissue weight, regardless of
      ovariectomy, suggesting its potential as a low-energy substitute for high-energy
      sweeteners. The low energy of DFAIII may contribute to decreased body fat, which
      may not be dependent on obesity.

PMID- 28436748
TI  - Disruption of tetR type regulator adeN by mobile genetic element confers elevated
      virulence in Acinetobacter baumannii.
AB  - Acinetobacter baumannii is an important human pathogen and considered as a major
      threat due to its extreme drug resistance. In this study, the genome of a hyper
      virulent MDR strain PKAB07 of A. baumannii isolated from an Indian patient was
      sequenced and analyzed to understand its mechanisms of virulence, resistance and
      evolution. Comparative genome analysis of PKAB07 revealed virulence and
      resistance related genes scattered throughout the genome, instead of being
      organized as an island, indicating the highly mosaic nature of the genome. Many
      intermittent horizontal gene transfer events, insertion sequence (IS) element
      insertions identified were augmenting resistance machinery and elevating the SNP
      densities in A. baumannii eventually aiding in their swift evolution. ISAba1, the
      most widely distributed insertion sequence in A. baumannii was found in multiple
      sites in PKAB07. Out of many ISAba1 insertions, we identified novel insertions in
      9 different genes wherein insertional inactivation of adeN (tetR type regulator)
      was significant. To assess the significance of this disruption in A. baumannii,
      adeN mutant and complement strains were constructed in A. baumannii ATCC 17978
      strain and studied. Biofilm levels were abrogated in the adeN knockout when
      compared with the wild type and complemented strain of adeN knockout. Virulence
      of the adeN knockout mutant strain was observed to be high, which was validated
      by in vitro experiments and Galleria mellonella infection model. The
      overexpression of adeJ, a major component of AdeIJK efflux pump observed in adeN
      knockout strain could be the possible reason for the elevated virulence in adeN
      mutant and PKB07 strain. Knocking out of adeN in ATCC strain led to increased
      resistance and virulence at par with the PKAB07. Disruption of tetR type
      regulator adeN by ISAba1 consequently has led to elevated virulence in this
      pathogen.

PMID- 28436749
TI  - Differential diagnosis of neonatal alloimmune thrombocytopenia: Type 2B von
      Willebrand disease.
AB  - At birth, severe thrombocytopenia without context of infection should mainly
      suggest neonatal alloimmune thrombocytopenia (NAIT), especially in case of a
      platelet count below 20 GL-1. We report two cases of severe neonatal
      thrombocytopenia, first suspected as being NAIT. Both had a platelet count below
      20 GL-1 with platelet clumps. The absence of alloantibodies and failure of
      platelet transfusion and intravenous immunoglobulins to improve the platelet
      count led to question the diagnosis and to evoke inherited bleeding disorders.
      Measurements of Von Willebrand factor (VWF) levels showed a marked reduction of
      VWF:RCo and a normal VWF:Ag, suggesting a type 2B Von Willebrand disease (VWD2B).
      Ristocetin-induced platelet aggregation could not be performed because of the
      very low platelet count. In the first case, after sequencing VWF exon 28, a
      heterozygous p.Leu1460Pro mutation was found consistent with VWD2B. In the second
      case, the genetic analysis of VWF exon 28 identified a homozygous mutation:
      p.Pro1337Leu confirming type VWD2B and also the p.Arg854Gln homozygous mutation
      in exon 20 confirming type 2N (ratio FVIII/VWF:Ag <0.5). The two cases underline
      that, even if NAIT remains the most common diagnosis in severe neonatal
      thrombocytopenia, it should be challenged in the absence of documented
      incompatibility, chronic evolution, or treatment failure. Diagnosis of VWD2B
      should be considered in early thrombocytopenia, even without familial history. In
      the cases presented, genotyping confirmed the subtype of VWD and helped to guide
      the therapeutic management of bleeding episodes.

PMID- 28436751
TI  - Analysing workplace violence towards health care staff in public hospitals using
      alternative ordered response models: the case of north-eastern Turkey.
AB  - The main objective of this article is to determine key factors that may have a
      significant effect on the verbal abuse, emotional abuse and physical assault of
      health care workers in north-eastern Turkey. A self-administered survey was
      completed by 450 health care workers in three well-established hospitals in
      Erzurum, Turkey. Because of the discrete and ordered nature of the dependent
      variable of the survey, the data were analysed using four distinctive ordered
      response models. Results revealed that several key variables were found to be a
      significant determinant of workplace violence, such as the type of health
      institution, occupational position, weekly working hours, weekly shift hours,
      number of daily patient contacts, age group of the respondents, experience in the
      health sector, training against workplace violence and current policies of the
      hospitals and the Turkish Ministry of Health.

PMID- 28436752
TI  - Quantitative MR imaging of intra-orbital structures: Tissue-specific measurements
      and age dependency compared to extra-orbital structures using multispectral
      quantitative MR imaging.
AB  - The orbit can be affected by unique pathologic conditions and often requires MRI
      evaluation. The purpose of this study was to investigate the age-related changes
      in multiple intra-orbital structures using quantitative MRI (qMRI). Thirty-eight
      subjects (20 males, 18 females; ages 0.5-87 years) underwent MRI with a mixed
      turbo spin echo sequence. T1 and T2 measurements were obtained within ROI in 6
      intra-orbital structures (medial and lateral rectus muscles, medial and lateral
      retrobulbar fat, lacrimal gland, and optic nerve), and compared with those of
      corresponding extra-orbital structures (masseter muscle, subcutaneous cheek fat,
      buccal fat, parotid gland, and frontal white matter). Statistical analyses were
      performed using Pearson's correlation coefficients. T1 and T2 values of the extra
      ocular muscles increased with age, with higher T1 and T2 values compared to the
      masseter muscles. Retrobulbar fat showed significant age-associated increases in
      T1 values in the lateral side and in T2 values in both sides. T1 and T2 values in
      the lacrimal gland increased with age, while the parotid gland showed an age
      associated increase in T2 values and decrease in T1 values. Optic nerves
      demonstrated age-related changes, similar to that of frontal white matter; rapid
      decreases with age in T1 and T2 times in early stages of life, and slight
      increases in T1 and T2 times later in life. Intra-orbital structures demonstrated
      specific qMRI measurements and aging patterns, which were different from extra
      orbital structures. Location-specific age-related changes of intra-orbital
      structures should be considered in the qMRI assessment of the orbital pathology.

PMID- 28436750
TI  - EMAP-II sensitize U87MG and glioma stem-like cells to temozolomide via induction
      of autophagy-mediated cell death and G2/M arrest.
AB  - Despite the fact that temozolomide (TMZ) has been widely accepted as the key
      chemotherapeutic agent to prolong the survival of patients with glioblastoma,
      failure and recurrence cases can still be observed in clinics. Glioma stem-like
      cells (GSCs) are thought to be responsible for the drug resistance. In this
      study, we investigate whether endothelial monocyte-activating polypeptide-II
      (EMAP-II), a pro-inflammatory cytokine, can enhance TMZ cytotoxicity on U87MG and
      GSCs or not. As described in prior research, GSCs have been isolated from U87MG
      and maintained in the serum-free DMEM/F12 medium containing EGF, b-FGF, and B27.
      TMZ and/or EMAP-II administration were performed for 72 h, respectively. The
      results showed that TMZ combined with EMAP-II inhibit the proliferation of U87MG
      and GSCs by a larger measure than TMZ single treatment by decreasing the IC50.
      EMAP-II also enhanced TMZ-induced autophagy-mediated cell death and G2/M arrest.
      Moreover, we found that EMAP-II functioned a targeted suppression on mTOR, which
      may involve in the anti-neoplasm mechanism. The results suggest that EMAP-II
      could be considered as a combined chemotherapeutic agent against glioblastoma by
      sensitizing U87MG and GSCs to TMZ.

PMID- 28436753
TI  - Prevalence and differences between type 1 and type 2 diabetes mellitus regarding
      female sexual dysfunction: a cross-sectional Egyptian study.
AB  - OBJECTIVE: To evaluate the female sexual dysfunction in both type 1 and type 2
      diabetes mellitus (DM). METHODS: This cross-sectional study was carried out at
      Suez Canal University Hospitals from the start of February 2015 to the end of May
      2016 among 189 married premenopausal women attending endocrinology and
      diabetology outpatient clinic for regular follow-up; 25 of whom refused to
      participate and 18 more were excluded due to incomplete data sets resulting in a
      final sample of 146 diabetic females. Ninety healthy women were recruited from
      the administrative staff at the hospital as a control group. Sexual dysfunction
      was assessed using female sexual function index (FSFI), a validated 19-item, self
      administered, screening questionnaire comprising the six major sexual domains:
      desire, arousal, lubrication, orgasm, satisfaction and pain. Responses to each
      question were reported and scored on 0-5 scale with 0 representing no sexual
      activity and 5 suggestive of normal sexual activity. RESULTS: Prevalence of
      sexual dysfunction was significantly higher in both type 1 and 2 DM groups (44
      and 25%, respectively) than in the control group (9%). FSFI mean total score was
      significantly lower in type 1 DM (21.1 +/- 3.9) than type 2 DM (26.4 +/- 4.2) and
      both were significantly lower than the control group (31.5 +/- 5.8). With regard
      to FSFI domains, mean values for desire, arousal, lubrication, orgasm,
      satisfaction and pain were significantly lower in both type 1 and type 2 DM
      groups when compared with the controls. CONCLUSION: FSD is a significant health
      problem among premenopausal diabetic Egyptian women. Type 1 DM women were more
      affected than type 2 DM that in turn was more affected than healthy control
      females.

PMID- 28436754
TI  - 5,7,3',4'-Tetramethoxyflavone protects chondrocytes from ER stress-induced
      apoptosis through regulation of the IRE1alpha pathway.
AB  - AIM OF THE STUDY: To investigate the roles of endoplasmic reticulum (ER)
      transmembrane sensor inositol-requiring enzyme-1 (IRE1)alpha signaling in ER
      stress-induced chondrocyte apoptosis, and to determine the molecular mechanisms
      underlying chondroprotective activity of 5,7,3',4'-tetramethoxyflavone (TMF) from
      Murraya exotica. MATERIALS AND METHODS: IRE1alpha was knocked down by siRNA
      transfection in chondrocytes, which were harvested from rats' knee cartilages.
      Chondrocytes with IRE1alpha deficiency were administrated with tunicamycin (TM)
      and TMF. Chondrocyte apoptosis was quantified by flow cytometry and DAPI/TUNEL
      staining. Expression of mRNA and proteins was quantified by quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) and western-blot, respectively.
      RESULTS: IRE1alpha deficiency significantly increased the rate of TM-induced
      chondrocyte apoptosis, down-regulated the expression of pro-survival factors
      XBP1S and Bcl-2, and up-regulated pro-apoptotic factors CHOP, p-JNK, and caspase
      3. TMF suppressed TM-induced chondrocyte apoptosis by activating the expression
      of IRE1alpha, which reversed the expression patterns of downstream pro-survival
      and pro-apoptotic factors due to IRE1alpha deficiency. CONCLUSION: The mechanism
      of TMF in protecting chondrocytes against ER stress-induced apoptosis might be
      associated with regulating the activity of ER sensor IRE1alpha and its downstream
      pathway.

PMID- 28436756
TI  - The role of attachment style in interpersonal psychotherapy for depressed
      adolescents.
AB  - OBJECTIVE(S): This study examined changes in depressed adolescents' reports of
      attachment anxiety and avoidance with interpersonal psychotherapy (IPT-A), and
      the relationship between attachment style and change in depression with IPT-A.
      METHOD: Forty adolescents (aged 12-17) participated in a 16-week randomized
      clinical trial of 4 adaptive treatment strategies for adolescent depression that
      began with IPT-A and augmented treatment for insufficient responders (n = 22) by
      adding additional IPT-A sessions (n = 11) or the antidepressant medication,
      fluoxetine (n = 11). Adolescents were 77.5% female and 22.5% male (mean age =
      14.8, SD = 1.8). Ten percent of adolescents were Latino. Racial composition was
      7.5% Asian, 7.5% American Indian/Alaska Native, 80.0% white, and 5.0% biracial.
      Measures of attachment style (Experience in Close Relationships Scale-Revised
      [ECR-R]) and depression (Children's Depression Rating Scale-Revised [CDRS-R])
      were administered at baseline and Weeks 8 and 16. RESULTS: Attachment Anxiety and
      Avoidance (ECR-R) decreased significantly from baseline to Week 16. Baseline
      Avoidance positively predicted greater reductions in depression (CDRS-R),
      controlling for fluoxetine. Reductions in Anxiety and Avoidance were also
      significantly associated with reductions in CDRS-R, controlling for fluoxetine.
      CONCLUSIONS: Adolescents' reports of attachment anxiety and avoidance are
      amenable to intervention with IPT-A. IPT-A may be particularly beneficial for
      adolescents who report a high level of avoidant attachment.

PMID- 28436755
TI  - Modes of Action for Mucosal Vaccine Adjuvants.
AB  - Vaccine adjuvants induce innate immune responses and the addition of adjuvants to
      the vaccine helps to induce protective immunity in the host. Vaccines utilizing
      live attenuated or killed whole pathogens usually contain endogenous adjuvants,
      such as bacterial cell wall products and their genomic nucleic acids, which act
      as pathogen-associated molecular patterns and are sufficient to induce adaptive
      immune responses. However, purified protein- or antigen-based vaccines, including
      component or recombinant vaccines, usually lose these endogenous innate immune
      stimulators, so the addition of an exogenous adjuvant is essential for the
      success of these vaccine types. Although this adjuvant requirement is mostly the
      same for parental and mucosal vaccines, the development of mucosal vaccine
      adjuvants requires the specialized consideration of adapting the adjuvants to
      characteristic mucosal conditions. This review provides a brief overview of
      mucosa-associated immune response induction processes, such as antigen uptake and
      dendritic cell subset-dependent antigen presentation. It also highlights several
      mucosal vaccine adjuvants from recent reports, particularly focusing on their
      modes of action.

PMID- 28436757
TI  - Bilingualism and age are continuous variables that influence executive function.
AB  - We analyzed the effects of bilingualism and age on executive function. We
      examined these variables along a continuum, as opposed to dichotomizing them. We
      investigated the impact that bilingualism and age have on two measures of
      executive control (Stroop and Flanker). The mouse-tracking paradigm allowed us to
      examine the continuous dynamics of the responses as participants completed each
      trial. First, we found that the Stroop effect was reduced with younger age and
      higher levels of bilingualism; however, no Bilingualism by Age interaction
      emerged. Second, after controlling for baseline, the Flanker effect was not
      influenced by bilingualism or age. These results support the notion that
      bilingualism is one way of enhancing some aspects of executive function -
      specifically those related to the Stroop task - across the adult life span. In
      sum, different levels of bilingualism, and different ages, result in varying
      degrees of executive function as measured by the Stroop task.

PMID- 28436758
TI  - Amphetamine-Type-Stimulants (ATS) Use and Homosexuality-Related Enacted Stigma
      Are Associated With Depression Among Men Who Have Sex With Men (MSM) in Two Major
      Cities in Vietnam in 2014.
AB  - BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by
      mental health concerns, including depression. Amphetamine-type-stimulants (ATS)
      use and homosexuality-related stigma and discrimination have been found
      associated with depression among MSM. OBJECTIVES: To assess the prevalence of
      depression and its associations with ATS use and homosexuality-related stigma and
      discrimination among MSM in Vietnam. METHODS: 622 MSM were conveniently recruited
      in Hanoi and Ho Chi Minh city, Vietnam, from September to December 2014. We
      collected information on demographic characteristics, ATS, alcohol and other drug
      use, sexual behaviors, homosexuality-related and discrimination stigma, and
      sexual sensation-seeking. Depression and suicidal thoughts were assessed by the
      Patient Health Questionnaire (PHQ-9). We assessed associations of depression with
      ATS use and homosexuality-related stigma and discrimination using logistic
      regression. RESULTS: Of 622 sampled MSM, 11.3% were classified as having major
      depression, 9.8% reported any suicidal thoughts in the last two weeks, 30.4% ever
      had used any ATS, 88.8% ever ad drank alcohol and 21.5% had ever used any other
      drugs. In multivariate analysis, depression was significantly associated with ATS
      use (Adjusted Odds Ratio [AOR: 2.20; (95% Confidence Interval (CI): 1.32-3.67],
      younger age of sexual debut with another man (AOR: 0.09; 95% CI: 0.02-0.50), and
      greater enacted homosexuality-related stigma (AOR: 1.97; 95% CI: 1.19-3.26).
      CONCLUSIONS: We found a moderate prevalence of depression among sampled MSM,
      which was associated with ATS use and enacted homosexuality-related stigma. We
      recommend integrating assessment and interventions regarding depression and
      methamphetamine use into gay-friendly, culturally adapted holistic HIV prevention
      for MSM in Vietnam.

PMID- 28436759
TI  - The roles of microRNAs in spinal cord injury.
AB  - BACKGROUND AND PURPOSE: Spinal cord injury (SCI) involves serious damage that can
      result in abnormal or absent motor and sensory functions and a disruption of
      autonomic function, and a series of pathological reactions occur after the
      injury. As a type of small non-coding RNA, microRNAs (miRNAs) have been verified
      to inhibit gene expression via post-transcriptional regulation. This review
      mainly focuses on recent advances regarding the roles of miRNAs following SCI.
      METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines were adopted. The studies regarding the roles of miRNAs following SCI
      were identified through PubMed, Embase and Web of Science. We summarise the
      changes in expression levels of miRNAs and discuss the roles of miRNAs after SCI.
      RESULTS: A total of 77 empirical studies meeting the inclusion criteria were
      identified. Existing studies showed that miRNAs were temporally altered and had
      effects on apoptosis, inflammation, angiogenesis, astrogliosis, oligodendrocyte
      development, axonal regeneration and remyelination after SCI. The alteration of
      miRNAs and the regulative action of pathological reactions can also provide
      opportunities for potential therapeutic interventions. "miRNA replacement
      therapy" aims to transfer miRNAs into diseased cells via delivery techniques and
      improve targeting effectiveness in cells, and this novel therapeutic tool
      provides a promising technique to promote the repair of SCI and reduces
      functional deficits. CONCLUSIONS: This review is helpful for understanding the
      underlying mechanisms of SCI and the potential clinical value of miRNAs. miRNAs
      have the potential to be attractive tools and targets for novel diagnostic and
      therapeutic approaches of SCI.

PMID- 28436760
TI  - Diabetes Management by Probiotics: Current Knowledge and Future Pespective.
AB  - Diabetes mellitus, a multifactorial disorder, is related to the intestinal
      microbiota via numerous molecular mechanisms. The vast increase in the prevalence
      of diabetes and its associated complications requires a natural and safe
      solution. There is a growing evidence of gut microbiota effi ciency in improving
      insulin resistance, impaired insulin secretion, and metabolic complications in
      diabetic patients. Probiotics are defi ned as live microorganisms that, when
      ingested in adequate amounts, exert health benefi ts to the host. Probiotics can
      increase insulin sensitivity and reduce autoimmune responses by modulating
      intestinal microbiota and decreasing the infl ammatory reactions and oxidative
      stress. Recent evidences show that the intestinal microbiota infl uences the host
      through modulating intestinal permeability and mucosal immune response,
      manipulating eating behaviors by appetite-regulating hormones, including agouti
      related protein (AgRP), glucagon like peptide-1 (GLP-1) and neuropeptide Y, and
      controlling gut endocannabinoid (eCB) system which is now believed to be
      associated with infl ammation and diabetes. Moreover, intestinal microbiota
      control the host metabolism by affecting energy extraction from food and by
      biochemically converting molecules derived from the host or from gut microbes
      themselves. Experimental studies and clinical trials support the hypothesis that
      the modulation of the intestinal microbiota by probiotics, especially
      Lactobacillus and Bifidobacterium strains may be effective in prevention and
      management of diabetes. This review will highlight the current evidences in
      probiotic effectiveness and future prospects for exploring probiotic therapy in
      prevention and control of diabetes.

PMID- 28436761
TI  - Androgen and Estrogen Shifts in Men Before and After Bariatric Surgery and Links
      to Vitamins and Trace Elements.
AB  - Androgens and estrogens play a key role regarding sexual life and reproduction.
      Along with hypotestosteronemia, obese men exhibit a 2-fold increase in estradiol
      concentration, adversely infl uencing these parameters. Estrogens and adipokines
      also infl uence bone metabolism, exerting a direct effect on vitamin D, calcium
      homeostasis and bone health. Bariatric procedures normalize some sex hormones,
      and may reverse several obesity-related conditions. Estrogens levels may remain
      elevated postoperatively, and despite its protective effect on the skeleton,
      bariatric patients are more prone to fractures when compared to the general
      population. Multiple nutritional defi cits are common after bariatric
      interventions, and hypozincemia is the most likely to negatively infl uence
      reproductive parameters. Zinc is an essential element for normal spermatogenesis,
      and severe hypozincemia is associated with infertility in both sexes. Vitamin D
      also acts as a regulator of several enzymes involved in steroid hormone
      production, and its defi ciency could impair reproductive function. Few studies
      have addressed changes in sex hormones and in reproductive function in the male
      bariatric population, as they represent a minority of surgical candidates.
      Although obesity rates and burden are similar for both sexes, society is more
      lenient with the obese male. Moreover, 73 % of overweight/obese men are satisfi
      ed with their health, causing body weight and obesity-related health problems to
      increase when they opt for bariatric surgery. In the present article, we discuss
      shifts of sex hormones before and after bariatric surgery, surgery impact on
      semen quality, skeletal health and nutrients, and new research directions
      regarding links between vitamin D, zinc, androgens and reproduction.

PMID- 28436764
TI  - Review of "Practical Neurology Visual Review, 2nd Edition," by Jose Biller and
      Alberto Espay.

PMID- 28436763
TI  - Review of "Surgical Neurophysiology: A Reference Guide to Intraoperative
      Neurophysiological Monitoring (IONM), 2nd Edition," by Faisal R. Jahangiri.

PMID- 28436762
TI  - Use of Dietary Vitamin Supplements and Risk of Thyroid Cancer: A Population-Based
      Case-Control Study in Connecticut.
AB  - : Certain dietary supplements have been reported to increase the risk of some
      cancers. Over half of the US population regularly uses dietary supplements.
      Thyroid cancer incidence has increased over the past several decades. However,
      few studies have investigated the association between dietary supplements and
      thyroid cancer. Thus, it is essential to clarify any association between dietary
      supplements and risk of thyroid cancer. MATERIALS AND METHODS: A population-based
      case-control study in Connecticut was conducted during 2010-2011 among 462
      histologically confi rmed incident thyroid cancer cases and 498 population-based
      controls. Dietary supplement intake was ascertained through in-person interviews
      and a food frequency questionnaire. Multivariate unconditional logistic
      regression models were used to estimate the risk of thyroid cancer and dietary
      supplement use. RESULTS: Overall, no statistically signifi cant associations were
      observed between dietary supplementation and thyroid cancer risk. Stratifi ed
      analyses revealed a suggestive protective effect on risk of papillary
      microcarcinoma among longterm (> 10 years) use of multivitamins (OR = 0.59, 95 %
      CI: 0.33, 1.04) and calcium supplementation (OR = 0.45, 95 % CI: 0.22, 0.93). An
      increased risk of large papillary thyroid cancers (tumor size > 1 cm) was
      observed among short-term (< 5 years) users of calcium supplements (OR = 2.24, 95
      % CI: 1.30, 3.88). DISCUSSION: No signifi cant associations were observed between
      supplementation and overall thyroid cancer risk. The different associations
      between calcium supplements and risk of papillary thyroid cancer by tumor size
      warrant further investigation.

PMID- 28436766
TI  - Editorial: Building a Qualified Neurodiagnostic Technology Workforce.

PMID- 28436768
TI  - Use of Posterior Root-Muscle Reflexes in Peripheral Nerve Surgery: A Case Report.
AB  - It is well established that a mixed-agent general anesthetic regimen of volatile
      gas and intravenous anesthetic or total intravenous anesthetic (TIVA) is required
      to obtain adequate transcranial motor-evoked potentials (TcMEPs) to detect and
      hopefully prevent injury during brain, spinal cord, and peripheral nerve surgery.
      But even under ideal general anesthetic conditions, TcMEPs are not always
      detectable in every muscle monitored, and are prone to anesthetic fade,
      especially when neuropathic or injured tissue is monitored. TcMEP sensitivity to
      general anesthesia can be especially problematic during peripheral nerve surgery
      where there is often only one or a few essential muscles required to provide
      adequate monitoring; thus, maximum fidelity is essential. However, there is an
      anesthetic-resistant high-fidelity modality available to successfully monitor the
      motor component of distant peripheral nerves originating from the cauda equina.
      Percutaneus transabdominal electrical stimulation elicits a relatively anesthetic
      resistant, robust motor response in muscles innervated by cauda equina nerve
      roots. We report the successful use of posterior root-muscle (PRM) reflex to
      monitor the decompression of the sciatic nerve at its bifurcation in a 22-year
      old female with a history of severe sciatic nerve neuropathic pain and muscle
      weakness following benign thigh tumor resection.

PMID- 28436769
TI  - Review of "Handbook for Clinical Research: Design, Statistics, and
      Implementation," by Flora M. Hammond, James F. Malec, Todd G. Nick, and Ralph M.
      Buschbacher.

PMID- 28436770
TI  - ASET-CEU Quiz.

PMID- 28436771
TI  - Comparison of Subdermal Needle and Surface Adhesive Stimulating Electrodes for
      Somatosensory Evoked Potential Monitoring during Anterior Cervical Discectomy and
      Fusion.
AB  - INTRODUCTION: Needle stick injuries remain a physical and psychological burden to
      healthcare workers. Noninvasive surface adhesive stimulating electrodes used to
      generate somatosensory evoked potentials can help decrease this risk. METHODS: We
      performed a retrospective observational study of patients who underwent anterior
      cervical discectomy and fusion (ACDF) surgery to determine the utility and
      variability of using surface adhesive stimulating electrodes. Our analysis for
      utility compared alarm (significant changes) frequency, defined by established
      alarm criteria, between subdermal needle (Group I) and surface adhesive
      electrodes (Group II). We compared the variability by comparing the frequency of
      alarms based on establishing baselines during various stages of the procedure.
      RESULTS: Between Group I and Group II, no significant differences were found in
      demographic, age, number of levels decompressed and fused, and length of surgery
      variability. However, stimulation intensity was significantly higher in Group II.
      Significant differences in the mean frequency of alarm of cortical, subcortical,
      and Erb's somatosensory evoked potential (SSEP) responses for the upper
      extremities between the two groups were only observed for the upper left Erb's
      point amplitude (p = 0.03) at retraction and upper right cortical amplitude at
      incision (p = 0.02). The frequency of alarms of the amplitude of left ulnar
      cortical responses from SSEPs using surface adhesives when baselines were
      established at the beginning of the procedure, at the time of incision, and at
      placement of retractors were 13.83 % (+/-14.08%), 7.50 % (+/-7.56%) and 3.42 %
      (+/-3.48%), respectively. Comparatively, the frequencies of alarms of the
      amplitude of left ulnar cortical responses from SSEPs using needle electrodes
      were 18.07 % (+/-22.85%), 12.13 % (+/-17.30%) and 7.37 % (+/-11.82%),
      respectively. Similar results were observed from frequency for alarms from the
      right ulnar SSEPs. CONCLUSION: This study found little significant difference
      between the frequencies of alarm in patients who had SSEP responses obtained
      using surface adhesive electrodes when compared to needle electrodes. This lack
      of significant difference was observed even when alarms were established at
      various stages of the surgery before any major manipulation. For short procedures
      monitoring the upper extremities only, surface adhesive electrodes may provide a
      reliable alternative to invasive needle electrodes.

PMID- 28436773
TI  - Waveform Window #37: Fact or Artifact, 2nd Edition.

PMID- 28436772
TI  - Skin Irritation during Video-EEG Monitoring.
AB  - OBJECTIVES: Video-EEG (VEEG) monitoring, indicated to characterize and diagnose
      seizures, is recorded over several days with electrodes glued to the patient's
      scalp. Our investigation was designed to determine the incidence of electrode
      related skin irritation during VEEG in the epilepsy monitoring unit (EMU) and
      implement a series of interventions to reduce the incidence of moderate to severe
      irritation. METHODS: Between May 2012 and March 2015, EMU patients were assessed
      for skin lesions before electrode placement and at discharge. Prospectively
      gathered demographic data included: age, gender, race/ethnicity, length of
      monitoring (LOM), skin prep medium (SPM) used, self-reported skin sensitivity,
      history of skin diseases, and skin products used on the day of admission. When
      present, electrode-related skin irritation was graded as mild, moderate, or
      severe. Data were collected before any intervention (baseline-group) and
      thereafter with each intervention: standardization (single SPM, raising
      awareness, monitoring for electrode-related discomfort); face washing; applying
      skin barrier; replacing tape with gauze; and using disposable electrodes.
      RESULTS: Data from 861 patients were analyzed (104-146 per group). At baseline,
      any skin irritation occurred in 27.3% of patients; it was moderate or severe in
      19.1%. LOM >=4 days and electrode position on facial skin were associated with
      significantly higher risk. All interventions reduced rates of skin irritation,
      but only the standardization intervention was statistically significant.
      CONCLUSIONS: During VEEG admissions, electrode-related skin irritation occurred
      in about one-third of patients; it was moderate to severe in one-fifth. A
      standardized care process with regular monitoring for discomfort led to
      significant improvement in the rate of irritation.

PMID- 28436774
TI  - The Effects of Positioning the Operative Limb on Tibial and Fibular Nerve
      Somatosensory Responses during Acetabulum Fracture Repair: A Report of Two
      Unusual Cases.
AB  - Our institution uses lower extremity somatosensory evoked potentials from the
      fibular (peroneal) and tibial nerves during posterior open reduction and internal
      fixation of the acetabulum to monitor the functional integrity of the sciatic
      nerve. This allows identification of compromised function caused by operative
      maneuvers. However, nonsurgical factors can also significantly affect the
      responses. In this article, we present one case where positioning of the leg and
      foot apparently caused diminished responses and was resolved by changing the
      manner of wrapping and securing the leg and foot. The second case is unusual
      because positioning improved the responses from being absent to identifiable and
      stable. Investigation of changes in peripheral responses should include
      examination of the position of the affected leg for ischemia and edema, and
      particularly the stimulation site for possible compromise.

PMID- 28436775
TI  - Psychogenic Nonepileptic Seizures versus Epileptic Seizures: An Unusual Case
      Report.
AB  - Psychogenic nonepileptic seizures may closely resemble epileptic seizures. Video
      EEG is an important tool in the diagnostic work-up to differentiate between
      seizures of neurological origin and nonepileptic events mimicking seizures. This
      article will review the case of a 30-year-old female presenting with a new onset
      of possible seizure activity and her stay in the epilepsy monitoring unit.

PMID- 28436777
TI  - Corrigendum.

PMID- 28436780
TI  - Truth Axes and the Transformation of Self.
AB  - Freud adhered to the idea that psychoanalysis is a science and that truth is one.
      The transition from a realistic epistemology to an epistemology of subjective
      idealism in psychoanalytic thought was accompanied by the splintering of the
      "one" realistic truth into a multiplicity of truths: realistic-correspondent,
      ideal, subjective-existential, intersubjective, coherent, and pragmatic truths.
      The present paper, employing the concept of "truth axes," explores these truths
      as they relate to basic human needs, self- states, and the structuring of
      subjectivity. Truth axes are posited as organizing principles of the psyche aimed
      at achieving stable images of reality across critical dimensions of the subject's
      life. Personality and experience render some axes dominant, while others remain
      foreclosed and dissociated. In this construal, the psychoanalytic process
      concerns the detailing, depicting, and understanding of the various truth axes.
      The psychological definition of truth illuminates its relation to clinical
      objectives and methodologies and emphasizes the ethical dimension involved in
      prioritization of truths. These ideas are illustrated by clinical vignettes.

PMID- 28436782
TI  - Subverting Space: An Exploration of a Dance Therapy Workshop Apparatus for
      Schizophrenics.
AB  - The authors created a dance workshop for schizophrenic patients designed to
      address their singular experience of space, in which the categories of interior
      and exterior do not function as limits. The space of the workshop, which,
      paradoxically, is thought in terms of the psychic space of schizophrenic patients
      by playing on its borderless quality, creates a continuity between the
      psychiatric hospital and the external world, and thus helps to prevent the
      segregation and isolation of such patients. This continuity is established on the
      basis of both the physical architecture of the workshop setting and the practice
      of dancing itself. The authors explore the hypothesis that, inside the particular
      space made possible by the apparatus of the workshop, schizophrenic patients
      benefit from the experience of movement, beginning with the pulse of rhythm,
      which establishes a consistency in time. By means of its repetitive character,
      the beat of music, like movement, accompanies and promotes the experience of
      continuity, which is the condition for any possible form of symbolizing. Two
      brief clinical illustrations show how this approach to dance therapy allows a
      moribund jouissance to be overturned and transformed into the aesthetic
      jouissance that characterizes the experience of dance.

PMID- 28436783
TI  - Recognizing the Patient's Criticism of the Analyst.
AB  - Difficulty hearing criticism of us by our patients continues to be widespread
      among clinicians and interferes with progress in treatment. Analysts may have
      trouble hearing criticism because it is well hidden in the patient's associations
      or because it is difficult for them to recognize their shortcomings. The author
      suggests that the analyst's failure to hear criticism prevents the patient from
      resolving what may be the final, unhealthy ties to past objects. With a lens
      deliberately trained on criticism in our patients' material, analysts may be
      surprised by the myriad forms of criticism that are present and by the importance
      of receptive listening.

PMID- 28436786
TI  - American Clinical Neurophysiology Society: EEG Guidelines Introduction.
AB  - This revision to the EEG Guidelines is an update incorporating current EEG
      technology and practice. "Standards of practice in clinical
      electroencephalography" (previously Guideline 4) has been removed. It is
      currently undergoing revision through collaboration among multiple medical
      societies and will become part of "Qualifications and Responsibilities of
      Personnel Performing and Interpreting Clinical Neurophysiology Procedures." The
      remaining guidelines are reordered and renumbered.

PMID- 28436787
TI  - Neurodiagnostic Laboratory Accreditation: An Overview.

PMID- 28436788
TI  - American Clinical Neurophysiology Society Guideline 3: A Proposal for Standard
      Montages to Be Used in Clinical EEG.
AB  - This revision to the EEG Guidelines is an update incorporating current
      electroencephalography technology and practice and was previously published as
      Guideline 6. A discussion of methodology for the appropriate selection of
      reference electrodes is added. In addition, montages are added to assist with
      localization of abnormal activity in mesial frontal and anterior temporal
      regions.

PMID- 28436790
TI  - ASET 57th Annual Conference Proceedings.

PMID- 28436789
TI  - American Clinical Neurophysiology Society Guideline 6: Minimum Technical
      Standards for EEG Recording in Suspected Cerebral Death.
AB  - This revision to the EEG Guidelines is an update incorporating current EEG
      technology and practice. The role of the EEG in making the determination of brain
      death is discussed as are suggested technical criteria for making the diagnosis
      of electrocerebral inactivity.

PMID- 28436791
TI  - American Clinical Neurophysiology Society Guideline 2: Guidelines for Standard
      Electrode Position Nomenclature.
AB  - This revision to the EEG Guidelines is an update incorporating current
      electroencephalography technology and practice and was previously published as
      Guideline 5. While the 10-10 system of electrode position nomenclature has been
      accepted internationally for almost two decades, it has not been used
      universally. The reasons for this and clinical scenarios when the 10-10 system
      provides additional localizing information are discussed in this revision. In
      addition, situations in which AF1/2, AF5/6, PO1/2 and PO5/6 electrode positions
      may be utilized for EEG recording are discussed.

PMID- 28436792
TI  - American Clinical Neurophysiology Society Guideline 7: Guidelines for EEG
      Reporting.
AB  - This EEG Guideline incorporates the practice of structuring a report of results
      obtained during routine adult electroencephalography. It is intended to reflect
      one of the current practices in reporting an EEG and serves as a revision of the
      previous guideline entitled "Writing an EEG Report." The goal of this guideline
      is not only to convey clinically relevant information, but also to improve
      interrater reliability for clinical and research use by standardizing the format
      of EEG reports. With this in mind, there is expanded documentation of the patient
      history to include more relevant clinical information that can affect the EEG
      recording and interpretation. Recommendations for the technical conditions of the
      recording are also enhanced to include post hoc review parameters and type of EEG
      recording. Sleep feature documentation is also expanded upon. More descriptive
      terms are included for background features and interictal discharges that are
      concordant with efforts to standardize terminology. In the clinical correlation
      section, examples of common clinical scenarios are now provided that encourages
      uniformity in reporting. Including digital samples of abnormal waveforms is now
      readily available with current EEG recording systems and may be beneficial in
      augmenting reports when controversial waveforms or important features are
      encountered.

PMID- 28436796
TI  - The Maureen Berkeley Award.

PMID- 28436794
TI  - ASET-CEU Quiz.

PMID- 28436797
TI  - ASET Position Statement on Unattended Patients during Standard
      Electroencephalogram (EEG) Procedures.

PMID- 28436798
TI  - ASET Position Statement on Core Curriculum as Education Pathway to Grow a
      Qualified Workforce.

PMID- 28436799
TI  - American Clinical Neurophysiology Society Guideline 4: Recording Clinical EEG on
      Digital Media.
AB  - Digital EEG recording systems are now widely available and relatively
      inexpensive. They offer multiple advantages over previous analog/paper systems,
      such as higher fidelity recording, signal postprocessing, automated detection,
      and efficient data storage. This document provides guidance for the creation of
      digital EEG recordings including (1) documentation of patient information, (2)
      notation of information during the recording, (3) digital signal acquisition
      parameters during the recording, (4) storage of digital information, and (5)
      display of digital EEG signals.

PMID- 28436800
TI  - American Clinical Neurophysiology Society Guideline 1: Minimum Technical
      Requirements for Performing Clinical Electroencephalography.

PMID- 28436801
TI  - American Clinical Neurophysiology Society Guideline 5: Minimum Technical
      Standards for Pediatric Electroencephalography.
AB  - This revision to the EEG Guidelines is an update incorporating the current
      electroencephalography technology and practice. It was previously published as
      Guideline 2. Similar to the prior guideline, it delineates the aspects of
      Guideline 1 that should be modified for neonates and young children. Recording
      conditions for photic stimulation and hyperventilation are revised to enhance the
      provocation of epileptiform discharges. Revisions recognize the difficulties
      involved in performing an EEG under sedation in young children. Recommended
      neonatal EEG montages are displayed for the reduced set of electrodes only since
      the montages in Guideline 3 should be used for a 21-electrode 10-20 system array.
      Neonatal documentation is updated to use current American Academy of Pediatrics
      term "postmenstrual age" rather than "conceptional age." Finally, because
      therapeutic hypothermia alters the prognostic value of neonatal EEG, the
      necessity of documenting the patient's temperature at the time of recording is
      emphasized.

PMID- 28436802
TI  - ASET Position Statement on Skin Safety during EEG Procedures - A Guideline to
      Improving Outcome.

PMID- 28436803
TI  - ASET Position Statement on Video EEG Data Management in Long Term Monitoring
      Studies.

PMID- 28436804
TI  - Editorial: Medical Editor Change.

PMID- 28436805
TI  - Review of Current Practice of Clinical Electroencephalography, 4th Edition, by
      John S. Ebersole, Aatif M. Husain, and Douglas R. Nordli.

PMID- 28436806
TI  - Review of Wyllie's Treatment of Epilepsy, 5th Edition, edited by Elaine Wyllie.

PMID- 28436807
TI  - ASET Position Statement on Skin Safety during EEG Procedures - A Guideline to
      Improving Outcome Addendum: Neonatal Continuous EEG.

PMID- 28436809
TI  - Review of Caplan's Stroke: A Clinical Approach, 4th Edition, by Louis R. Caplan.

PMID- 28436808
TI  - Kathleen Mears Memorial Lecture: Go for the Gold: Essential Skills for
      Neurodiagnostic Practitioners.

PMID- 28436811
TI  - ASET-CEU Quiz.

PMID- 28436812
TI  - Retrospective Waveform Analysis of Transcranial Motor Evoked Potentials (MEP) to
      Identify Early Predictors of Impending Motor Deficits in Spinal Surgeries.
AB  - PURPOSE: Although there are guidelines analyzing transcranial motor evoked
      potentials (MEP) waveform criteria, they vary widely and are not applied
      universally during intraoperative neurophysiologic monitoring (IONM). The
      objective is to generate hypotheses to identify early and reliable MEP waveform
      characteristics prior to complete loss of MEP to predict impending motor spinal
      cord injuries during spinal surgeries. The ultimate goal is to enhance real-time
      feedback to prevent injury or detect reversible spinal cord damage. METHODS:
      Fifteen true positive cases of persistent intraoperative MEP loss and new
      postoperative motor deficits were retrospectively identified from 2011 to 2013.
      Waveform characteristics of latency, amplitude, duration, phases, and area-under
      the-curve (AUC) were measured, and an intraoperative spinal cord index (ISCI) was
      calculated for 5 traces prior to complete MEP loss. ISCI = [amplitude x duration
      x (phases+1) x AUC]/latency. RESULTS: Out of 22 muscles in 15 cases, latency
      increased in 2, duration decreased in 12, amplitude decreased in 13, AUC
      decreased in 13, and ISCI decreased in 14. In 11 out of 15 cases (73%), ISCI
      dropped > 40% in at least one muscle before MEP were completely lost. Thirteen
      cases had concurrent somatosensory evoked potentials (SSEP) changes, 9 out of 13
      had > 50% decrease in SSEP: 2 out of 9 changed before MEP, 5 out of 9
      simultaneously, and 2 out of 9 after. CONCLUSIONS: In these cases of motor
      injury, smaller and simpler MEP waveforms preceded complete loss of signal. An
      ISCI 40% drop could be tested as a warning threshold for impending motor
      compromise in future prospective studies and lead to eventual standardization to
      predict irreversible postoperative deficits.

PMID- 28436814
TI  - Credentialing Organizations.

PMID- 28436813
TI  - RF Heating of Gold Cup and Conductive Plastic Electrodes during Simultaneous EEG
      and MRI.
AB  - PURPOSE: To investigate the heating of EEG electrodes during magnetic resonance
      imaging (MRI) scans and to better understand the underlying physical mechanisms
      with a focus on the antenna effect. MATERIALS AND METHODS: Gold cup and
      conductive plastic electrodes were placed on small watermelons with fiberoptic
      probes used to measure electrode temperature changes during a variety of 1.5T and
      3T MRI scans. A subset of these experiments was repeated on a healthy human
      volunteer. RESULTS: The differences between gold and plastic electrodes did not
      appear to be practically significant. For both electrode types, we observed
      heating below 4 degrees C for straight wires whose lengths were multiples of 1/2
      the radiofrequency (RF) wavelength and stronger heating (over 15 degrees C) for
      wire lengths that were odd multiples of 1/4 RF wavelength, consistent with the
      antenna effect. CONCLUSIONS: The antenna effect, which has received little
      attention so far in the context of EEG-MRI safety, can play as significant a role
      as the loop effect (from electromagnetic induction) in the heating of EEG
      electrodes, and therefore wire lengths that are odd multiples of 1/4 RF
      wavelength should be avoided. These results have important implications for the
      design of EEG electrodes and MRI studies as they help to minimize the risk to
      patients undergoing MRI with EEG electrodes in place.

PMID- 28436815
TI  - Moyamoya in a Patient with FIRES: A First Case Report.
AB  - Febrile infection-related epilepsy syndrome (FIRES) is a form of epileptic
      encephalopathy with severe refractory epilepsy that presents in previously
      healthy, school-aged children after significant febrile illness with concomitant
      rise in body temperature. Suspected causes include genetic or acquired
      channelopathies, as well as mitochondrial disturbances. In FIRES, the EEG shows
      diffuse slowing, generalized, and/or multifocal discharges. Seizures are present
      and resistant to treatment. Moyamoya angiopathy (MMA) is characterized by
      progressive stenosis of cerebral arteries and subsequent development of a network
      of collateral circulation that is prone to rupture. We present here a case of a 6
      year-old patient with a postfebrile illness, acute and explosive bilateral
      independent seizure onset that was most consistent with FIRES, but also with
      imaging evidence of right-sided-only MMA. Our patient demonstrated two diseases
      not described together previously in the literature. It is unknown whether this
      patient's MMA is related to FIRES. In spite of successful corrective surgery
      (encephaloduroarteriosynangiosis), the patient continues to suffer from
      intractable seizures (mostly on the right) and apparent mild encephalopathy. The
      impact of our interventions (surgery, antiepileptic medication) is unclear. In
      this article, we describe a case of MMA and FIRES, and the history, physical,
      laboratory, imaging, and developmental elements of the 6-year-old patient with
      previously normal development.

PMID- 28436816
TI  - (Almost) Lost at SEA: An Unusual Cause of Cortical Blindness.
AB  - A middle-aged man with a history of type 2 diabetes mellitus, hypertension,
      hyperlipidemia, prior cerebral vascular accident, and remote history of
      generalized seizure disorder presented with worsening right-sided visual deficits
      and focal seizures. On examination the patient had dense homonymous hemianopsia
      on the right side. He was initially diagnosed with a stroke and underwent further
      investigation for potential causes. However, upon further review, magnetic
      resonance imaging (MRI) findings and repeat examination were more consistent with
      seizure-related effects on cortical brain matter as the cause of his visual
      disturbances rather than stroke. An EEG confirmed focal seizures from the left
      posterior quadrant of the brain, and the diagnosis of status epilepticus
      amauroticus (SEA) was made. The hemianopsia resolved with antiepileptic
      treatment.

PMID- 28436817
TI  - Waveform Window #38: EEG Stages of Neonatal Hypoxic Ischemic Encephalopathy: From
      Background Suppression to Resolution of Neonatal Seizures.

PMID- 28436818
TI  - Dimensional Analysis: An Alternative Method for Converting between Interrelated
      Units of both Timebase and Sensitivity in EEG.
AB  - Neurodiagnostics professionals expected to perform EEG calculations involving
      timebase and sensitivity may benefit from an additional method in which to solve
      for the answers. Dimensional analysis (DA) is an efficient, organized method that
      generates answers in a consolidated context. Its coherent, streamlined mechanism
      allows for efficient computations involving sets of values with diametric units.
      One of its key advantages is its ability to emphasize conceptualization, which
      may be attractive to those with that mathematical personality. Its usefulness
      beyond neurodiagnostics is profound and includes assisting domestically inclined
      individuals with mathematical conversions related to home projects and proper
      cooking times. Several examples of both EEG and home-life applications are
      provided to assist with acclimation.

PMID- 28436820
TI  - sRNA-mediated activation of gene expression by inhibition of 5'-3' exonucleolytic
      mRNA degradation.
AB  - Post-transcriptional control by small regulatory RNA (sRNA) is critical for rapid
      adaptive processes. sRNAs can directly modulate mRNA degradation in
      Proteobacteria without interfering with translation. However, Firmicutes have a
      fundamentally different set of ribonucleases for mRNA degradation and whether
      sRNAs can regulate the activity of these enzymes is an open question. We show
      that Bacillus subtilis RoxS, a major trans-acting sRNA shared with Staphylococus
      aureus, prevents degradation of the yflS mRNA, encoding a malate transporter. In
      the presence of malate, RoxS transiently escapes from repression by the NADH
      sensitive transcription factor Rex and binds to the extreme 5'-end of yflS mRNA.
      This impairs the 5'-3' exoribonuclease activity of RNase J1, increasing the half
      life of the primary transcript and concomitantly enhancing ribosome binding to
      increase expression of the transporter. Globally, the different targets regulated
      by RoxS suggest that it helps readjust the cellular NAD+/NADH balance when
      perturbed by different stimuli.

PMID- 28436821
TI  - Hydrological modeling of Fecal Indicator Bacteria in a tropical mountain
      catchment.
AB  - The occurrence of pathogen bacteria in surface waters is a threat to public
      health worldwide. In particular, inadequate sanitation resulting in high
      contamination of surface water with pathogens of fecal origin is a serious issue
      in developing countries such as Lao P.D.R. Despite the health implications of the
      consumption of contaminated surface water, the environmental fate and transport
      of pathogens of fecal origin and their indicators (Fecal Indicator Bacteria or
      FIB) are still poorly known in tropical areas. In this study, we used
      measurements of flow rates, suspended sediments and of the FIB Escherichia coli
      (E. coli) in a 60-ha catchment in Northern Laos to explore the ability of the
      Soil and Water Assessment Tool (SWAT) to simulate watershed-scale FIB fate and
      transport. We assessed the influences of 3 in-stream processes, namely bacteria
      deposition and resuspension, bacterial regrowth, and hyporheic exchange (i.e.
      transient storage) on predicted FIB numbers. We showed that the SWAT model in its
      original version does not correctly simulate small E. coli numbers during the dry
      season. We showed that model's performance could be improved when considering the
      release of E. coli together with sediment resuspension. We demonstrated that the
      hyporheic exchange of bacteria across the Sediment-Water Interface (SWI) should
      be considered when simulating FIB concentration not only during wet weather, but
      also during the dry season, or baseflow period. In contrast, the implementation
      of the regrowth process did not improve the model during the dry season without
      inducing an overestimation during the wet season. This work thus underlines the
      importance of taking into account in-stream processes, such as deposition and
      resuspension, regrowth and hyporheic exchange, when using SWAT to simulate FIB
      dynamics in surface waters.

PMID- 28436819
TI  - Insight into the evolution of microbial metabolism from the deep-branching
      bacterium, Thermovibrio ammonificans.
AB  - Anaerobic thermophiles inhabit relic environments that resemble the early Earth.
      However, the lineage of these modern organisms co-evolved with our planet. Hence,
      these organisms carry both ancestral and acquired genes and serve as models to
      reconstruct early metabolism. Based on comparative genomic and proteomic
      analyses, we identified two distinct groups of genes in Thermovibrio
      ammonificans: the first codes for enzymes that do not require oxygen and use
      substrates of geothermal origin; the second appears to be a more recent
      acquisition, and may reflect adaptations to cope with the rise of oxygen on
      Earth. We propose that the ancestor of the Aquificae was originally a hydrogen
      oxidizing, sulfur reducing bacterium that used a hybrid pathway for CO2 fixation.
      With the gradual rise of oxygen in the atmosphere, more efficient terminal
      electron acceptors became available and this lineage acquired genes that
      increased its metabolic flexibility while retaining ancestral metabolic traits.

PMID- 28436822
TI  - Distinguishing homogeneous-heterogeneous degradation of norfloxacin in a
      photochemical Fenton-like system (Fe3O4/UV/oxalate) and the interfacial reaction
      mechanism.
AB  - This study demonstrated the efficient degradation of a typical bio-refractory
      antibiotic norfloxacin (NOR) in a photochemical iron oxides/oxalate system
      adopting magnetic catalyst (Fe3O4/UV/Ox). It was found that the in-situ generated
      HO was the main reactive oxygen species (ROS) but CO2- could also participate in
      the NOR degradation to form formylate organic intermediates. Besides, NOR would
      be degraded via an interesting pathway comprising an initial lag and a subsequent
      rapid period, where the former could be eliminated by introducing the pre
      dissolution of Fe3O4 particles. Furthermore, specific comparative investigations
      and surface characterizations of pre-adsorbed Fe3O4 particles had evidenced that
      the existence of surface-bound iron-Ox complexes would be critical for the
      heterogeneous photochemical dissolution of Fe3O4 and effectively initiated the
      subsequent homogeneous-heterogeneous NOR degradation. Finally, a comprehensive
      distinguishing reaction mechanism was proposed including a homogeneous
      heterogeneous iron cycle on the solid-water interface and a series of homogeneous
      radical reactions. Therein, complexation instead of photochemical reduction would
      be dominant during the whole dissolution process even under UV irradiation. Rapid
      electrons exchange would occur photochemically between FeII and FeIII in the
      octahedral sites, further weakening the surface Fe-O bonds and accelerating its
      breakaway from the bulk Fe3O4 structure. This work could distinguish the complex
      heterogeneous/homogeneous reactions in the photochemical in-situ chemical
      oxidation systems that utilize naturally abundant iron oxides and polycarboxylic
      acids.

PMID- 28436823
TI  - Flocculation and antimicrobial properties of a cationized starch.
AB  - In this study, a series of cationized starch-based flocculants (starch-3-chloro-2
      hydroxypropyl triethyl ammonium chloride, St-CTA) containing various quaternary
      ammonium salt groups on the starch backbone were prepared using a simple
      etherification reaction. All of the prepared starch-based flocculants show
      effective performance for the flocculation of kaolin suspension, two bacterial
      (Escherichia coli and Staphylococcus aureus) suspensions, and two contaminant
      mixtures (kaolin and each bacterium) under most pH conditions. St-CTA with a high
      substitution degree of CTA demonstrates improved contaminant removal efficiency
      because of the strong cationic nature of the grafted quaternary ammonium salt
      groups and the charge naturalization flocculation effect. The antibacterial
      effects of St-CTA were also evaluated, considering that many quaternary ammonium
      salt compounds elicit bactericidal effects. Three-dimensional excitation-emission
      matrix spectra and direct cell morphological observation under scanning electron
      microscopy reveal that the starch-based flocculants exhibit better antibacterial
      effects on the Gram-negative bacterium E. coli than on the Gram-positive
      bacterium S. aureus. The thicker cell wall due to the presence of abundant
      peptidoglycan and teichoic acids of S. aureus than E. coli explains the uneasy
      breakage of S. aureus cell wall after being attacked by the cationized starch
      based flocculants.

PMID- 28436824
TI  - Efficient treatment of aniline containing wastewater in bipolar membrane
      microbial electrolysis cell-Fenton system.
AB  - Aniline-containing wastewater can cause significant environmental problems and
      threaten the humans's life. However, rapid degradation of aniline with cost
      efficient methods remains a challenge. In this work, a novel microbial
      electrolysis cell with bipolar membrane was integrated with Fenton reaction (MEC
      Fenton) for efficient treatment of real wastewater containing a high
      concentration (4460 +/- 52 mg L-1) of aniline. In this system, H2O2 was in situ
      electro-synthesized from O2 reduction on the graphite cathode and was
      simultaneously used as source of OH for the oxidation of aniline wastewater under
      an acidic condition maintained by the bipolar membrane. The aniline was
      effectively degraded following first-order kinetics at a rate constant of 0.0166
      h-1 under an applied voltage of 0.5 V. Meanwhile, a total organic carbon (TOC)
      removal efficiency of 93.1 +/- 1.2% was obtained, revealing efficient
      mineralization of aniline. The applicability of bipolar membrane MEC-Fenton
      system was successfully demonstrated with actual aniline wastewater. Moreover,
      energy balance showed that the system could be a promising technology for removal
      of biorefractory organic pollutants from wastewaters.

PMID- 28436825
TI  - Integrated ecological and chemical food web accumulation modeling explains PAH
      temporal trends during regime shifts in a shallow lake.
AB  - Shallow lakes can switch suddenly from a turbid situation with high
      concentrations of phytoplankton and other suspended solids to a vegetated state
      with clear water, and vice versa. These alternative stable states may have a
      substantial impact on the fate of hydrophobic organic compounds (HOCs). Models
      that are fit to simulate impacts from these complex interactions are scarce. We
      developed a contaminant fate model which is linked to an ecosystem model (PCLake)
      for shallow lakes. This integrated model was successful in simulating long-term
      dynamics (1953-2012) of representative polycyclic aromatic hydrocarbons (PAHs) in
      the main biotic and abiotic components in a large shallow lake (Chaohu in China),
      which has undergone regime shifts in this period. Historical records from
      sediment cores were used to evaluate the model. The model revealed that regime
      shifts in shallow lakes had a strong impact on the fate of less hydrophobic
      compounds due to the large storage capacity of macrophytes, which accumulated up
      to 55.6% of phenanthrene in the clear state. The abrupt disappearance of
      macrophytes after the regime shift resulted in a sudden change in phenanthrene
      distribution, as the sediment became the major sink. For more hydrophobic
      compounds such as benzo(a)pyrene, the modeled impact of the regime shift was
      negligible for the whole environment, yet large for biotic compartments. This
      study is the first to provide a full mechanistic analysis of the impact of regime
      shifts on the fate of PAHs in a real lake ecosystem.

PMID- 28436826
TI  - Degradation of nitro-based pharmaceuticals by UV photolysis: Kinetics and
      simultaneous reduction on halonitromethanes formation potential.
AB  - This study investigated the degradation kinetics and halonitromethanes formation
      potential (HNMsFP) of two nitro-based pharmaceuticals (i.e., ranitidine (RNTD)
      and nizatidine (NZTD)) during ultraviolet (UV) photolysis. It was found that the
      degradation kinetics of RNTD and NZTD exhibited pH-dependent trends, in
      accordance with their deprotonation equilibria. The neutral species of RNTD and
      NZTD were more photo-reactive than their corresponding deprotonated species, with
      their specific fluence-based first-order rate constants varying in the range of
      5.64-31.90 m2 E-1. Both the RNTD and NZTD were prone precursors of HNMs (with
      molar yields of 5.6+/- 0.3% and 4.7+/- 0.4%, respectively at pH 7.0). Acidic and
      neutral circumstances facilitated the HNMs formation. The UV photolysis of RNTD
      and NZTD could reduce their HNMsFP simultaneously. Positive linear relationships
      between residual RNTD or NZTD concentration and HNMsFP were observed and the
      denitration during the UV photolysis accounted for the HNMsFP reduction. With the
      mandatory UV disinfection fluences in China (i.e. 20-80 mJ cm-2), the effective
      abatement of RNTD and NZTD and their HNMsFP could not be fully achieved,
      highlighting the necessity of increasing UV fluence or developing UV-based
      advanced oxidation process in future.

PMID- 28436827
TI  - Reductive precipitation of sulfate and soluble Fe(III) by Desulfovibrio vulgaris:
      Electron donor regulates intracellular electron flow and nano-FeS
      crystallization.
AB  - Fully understanding the metabolism of SRB provides fundamental guidelines for
      allowing the microorganisms to provide more beneficial services in water
      treatment and resource recovery. The electron-transfer pathway of sulfate
      respiration by Desulfovibrio vulgaris is well studied, but still partly
      unresolved. Here we provide deeper insight by comprehensively monitoring
      metabolite changes during D. vulgaris metabolism with two electron donors,
      lactate and pyruvate, in presence or absence of citrate-chelated soluble FeIII as
      an additional competing electron acceptor. H2 was produced from lactate oxidation
      to pyruvate, but pyruvate oxidation produced mostly formate. Accumulation of
      lactate-originated H2 during lag phases inhibited pyruvate transformation to
      acetate. Sulfate reduction was initiated by lactate-originated H2, but MQ
      mediated e- flow initiated sulfate reduction without delay when pyruvate was the
      donor. When H2-induced electron flow gave priority to FeIII reduction over
      sulfate reduction, the long lag phase before sulfate reduction shortened the time
      for iron-sulfide crystallite growth and led to smaller mackinawite (Fe1+xS)
      nanocrystallites. Synthesizing all the results, we propose that electron flow
      from lactate or pyruvate towards SO42- reduction to H2S are through at least
      three routes that are regulated by the e- donor (lactate or pyruvate) and the
      presence or absence of another e- acceptor (FeIII here). These routes are not
      competing, but complementary: e.g., H2 or formate production and oxidation were
      necessary for sulfite and disulfide/trisulfide reduction to sulfide. Our study
      suggests that the e- donor provides a practical tool to regulate and optimize SRB
      predominant bioremediation systems.

PMID- 28436828
TI  - Sensory profile and volatile aroma composition of reduced alcohol Merlot wines
      fermented with Metschnikowia pulcherrima and Saccharomyces uvarum.
AB  - Strategies for production of wines containing lower alcohol concentrations are in
      strong demand, for reasons of quality, health, and taxation. Development and
      application of wine yeasts that are less efficient at transforming grape sugars
      into ethanol has the potential to allow winemakers the freedom to make lower
      alcohol wines from grapes harvested at optimal ripeness, without the need for
      post-fermentation processes aimed at removing ethanol. We have recently shown
      that two non-conventional wine yeast species Metschnikowia pulcherrima and
      Saccharomyces uvarum were both able to produce wine with reduced alcohol
      concentration. Both species produced laboratory-scale wines with markedly
      different volatile aroma compound composition relative to Saccharomyces
      cerevisiae. This work describes the volatile composition and sensory profiles of
      reduced-alcohol pilot-scale Merlot wines produced with M. pulcherrima and S.
      uvarum. Wines fermented with M. pulcherrima contained 1.0% v/v less ethanol than
      S. cerevisiae fermented wines, while those fermented with S. uvarum showed a 1.7%
      v/v reduction in ethanol. Compared to S. cerevisiae ferments, wines produced with
      M. pulcherrima showed higher concentrations of ethyl acetate, total esters, total
      higher alcohols and total sulfur compounds, while wines fermented with S. uvarum
      were characterised by the highest total concentration of higher alcohols.
      Sensorially, M. pulcherrima wines received relatively high scores for sensory
      descriptors such as red fruit and fruit flavour and overall exhibited a sensory
      profile similar to that of wine made with S. cerevisiae, whereas the main sensory
      descriptors associated with wines fermented with S. uvarum were barnyard and
      meat. This work demonstrates the successful application of M. pulcherrima
      AWRI3050 for the production of pilot-scale red wines with reduced alcohol
      concentration and highlights the need for rigorous evaluation of non-conventional
      yeasts with regard to their sensory impacts.

PMID- 28436829
TI  - Modelling the effect of combined antimicrobials: A base model for multiple
      hurdles.
AB  - Combining antimicrobials to reduce microbial growth and to combat the potential
      impact of antimicrobial resistance is an important subject both in foods and in
      pharmaceutics. Modelling of combined treatments designed to reduce or eliminate
      microbial contamination in foods (microbiological predictive modelling) has
      become commonplace. Two main reference models are used to analyse mixtures: the
      Bliss Independence and the Loewe reference models (LRM). By using optical density
      to analyse the growth of Aeromonas hydrophila, Cronobacter sakazakii and
      Escherichia coli in combined NaCl/NaCl (a mock combination experiment) and
      combined NaCl/KCl experiments, previous models for combined antimicrobials in
      foods, based on the Bliss approach, were shown to be inconsistent and that models
      based on the LRM more applicable. The LRM was shown, however, to be valid only in
      the specific cases where the concentration exponents of all components in a
      mixture were identical. This is assured for a mock combination experiment but not
      for a true mixture. This, essentially, invalidates the LRM as a general reference
      model. A new model, based on the LRM but allowing for mixed exponents, was used
      to analyse the combined inhibition data, and concluded that the NaCl/KCl system
      gave the additive effect expected from literature studies. This study suggests
      the need to revise current models used to analyse combined effects.

PMID- 28436830
TI  - Antimicrobial activity of free and liposome-encapsulated thymol and carvacrol
      against Salmonella and Staphylococcus aureus adhered to stainless steel.
AB  - Antimicrobial activity of thymol, carvacrol and thymol/carvacrol liposomes (TCL)
      was evaluated against two bacterial pools, each one consisting of four strains of
      Staphylococcus aureus or Salmonella enterica. TCL were prepared using thin-film
      hydration, showing 270.20nm average diameter (polydispersity index of 0.33) and
      zeta potential of +39.99mV. Minimum inhibitory concentration (MIC) of thymol,
      carvacrol and TCL against S. aureus pool was 0.662mg/ml, while MIC for Salmonella
      pool was 0.331mg/ml for thymol and carvacrol, and for TCL was 0.662mg/ml.
      Bacterial pools (8.0logCFU/ml), allowed in contact on stainless steel AISI 304
      coupons in UHT skim milk for 15min, resulted in adhered populations of 5.6
      6.1logCFU/cm2. Adhered S. aureus (+/-6.1logCFU/cm2) were inhibited after 1-min
      and 10-min treatments using thymol or carvacrol at MIC and 2.0 MIC. Reductions of
      1.47-1.76logCFU/cm2 and 1.87-2.04logCFU/cm2 were obtained using 0.5 MIC of thymol
      and carvacrol, respectively. A 10-min contact with free (MIC and 2.0 MIC) and
      encapsulated (MIC) antimicrobials inhibited attached Salmonella (+/
      6.0logCFU/cm2); however, after 1-min of contact, 2.0 MIC of thymol and carvacrol
      were not able to inactivate adhered Salmonella MIC of TCL inactivated S. aureus
      and Salmonella after 10min; however, after 1-min contact, adhered S. aureus and
      Salmonella populations were decreased in 1.62logCFU/cm2 and 2.01logCFU/cm2,
      respectively. Considering antimicrobial concentrations and contact times, thymol,
      carvacrol, and TCL could be employed in food-contact surfaces to prevent biofilm
      formation at early stages of bacterial attachment. Further investigations should
      be performed considering long-term antibacterial effects of TCL.

PMID- 28436831
TI  - Gamma power in rural Pakistani children: Links to executive function and verbal
      ability.
AB  - Children in low- and middle-income countries are at high risk of cognitive
      deficits due to environmental deprivation that compromises brain development.
      Despite the high prevalence of unrealized cognitive potential, very little is
      known about neural correlates of cognition in this population. We assessed
      resting EEG power and cognitive ability in 105 highly disadvantaged 48-month-old
      children in rural Pakistan. An increase in EEG power in gamma frequency bands (21
      30Hz and 31-45Hz) was associated with better executive function. For girls, EEG
      gamma power also related to higher verbal IQ. This study identifies EEG gamma
      power as a neural marker of cognitive function in disadvantaged children in low-
      and middle-income countries. Elevated gamma power may be a particularly important
      protective factor for girls, who may experience greater deprivation due to gender
      inequality.

PMID- 28436832
TI  - Ventral striatal activity links adversity and reward processing in children.
AB  - Adversity impacts many aspects of psychological and physical development
      including reward-based learning and decision-making. Mechanisms relating
      adversity and reward processing in children, however, remain unclear. Here, we
      show that adversity is associated with potentiated learning from positive
      outcomes and impulsive decision-making, but unrelated to learning from negative
      outcomes. We then show via functional magnetic resonance imaging that the link
      between adversity and reward processing is partially mediated by differences in
      ventral striatal response to rewards. The findings suggest that early-life
      adversity is associated with alterations in the brain's sensitivity to rewards
      accounting, in part, for the link between adversity and altered reward processing
      in children.

PMID- 28436833
TI  - Proactive control in early and middle childhood: An ERP study.
AB  - Children experience important cognitive control improvements in the transition to
      school. This study examined 4-5-year-olds' (n=17) and 7-8-year-olds' (n=22)
      ability to proactively deploy cognitive control. Children performed a cued task
      switching paradigm presenting them with a cue indicating which attribute, color
      or shape, they should use to sort the upcoming stimulus. Following both cue and
      stimulus, we analyzed two event-related potentials: the P2 and P3, positive peaks
      reflecting sensory and attentional components of cognitive control, respectively.
      Following the cue, we also analyzed a positive slow-wave, indexing working memory
      engagement. We predicted that on switch trials, which required switching tasks,
      proactive control would result in larger cue-P3 amplitudes, reflecting
      recognition of the need to switch, and larger slow-wave amplitudes, reflecting
      maintenance of the new task-sets over the post-cue delay. This pattern was
      observed in both age groups. At the stimulus, in switch trials, both age groups
      had shorter stimulus-P2 latencies, consistent with processing facilitation. These
      results suggest that both 4-5- and 7-8-year-olds engaged cognitive control
      proactively. Older children, however, demonstrated better performance and larger
      cue-P2 amplitudes, suggesting more effective proactive control engagement in
      middle childhood.

PMID- 28436834
TI  - Active auditory experience in infancy promotes brain plasticity in Theta and
      Gamma oscillations.
AB  - Language acquisition in infants is driven by on-going neural plasticity that is
      acutely sensitive to environmental acoustic cues. Recent studies showed that
      attention-based experience with non-linguistic, temporally-modulated auditory
      stimuli sharpens cortical responses. A previous ERP study from this laboratory
      showed that interactive auditory experience via behavior-based feedback (AEx),
      over a 6-week period from 4- to 7-months-of-age, confers a processing advantage,
      compared to passive auditory exposure (PEx) or maturation alone (Naive Control,
      NC). Here, we provide a follow-up investigation of the underlying neural
      oscillatory patterns in these three groups. In AEx infants, Standard stimuli with
      invariant frequency (STD) elicited greater Theta-band (4-6Hz) activity in Right
      Auditory Cortex (RAC), as compared to NC infants, and Deviant stimuli with rapid
      frequency change (DEV) elicited larger responses in Left Auditory Cortex (LAC).
      PEx and NC counterparts showed less-mature bilateral patterns. AEx infants also
      displayed stronger Gamma (33-37Hz) activity in the LAC during DEV discrimination,
      compared to NCs, while NC and PEx groups demonstrated bilateral activity in this
      band, if at all. This suggests that interactive acoustic experience with non
      linguistic stimuli can promote a distinct, robust and precise cortical pattern
      during rapid auditory processing, perhaps reflecting mechanisms that support fine
      tuning of early acoustic mapping.

PMID- 28436836
TI  - Enhancing Detection of SSVEPs for a High-Speed Brain Speller Using Task-Related
      Component Analysis.
AB  - OBJECTIVE: This study proposes and evaluates a novel data-driven spatial
      filtering approach for enhancing steady-state visual evoked potentials (SSVEPs)
      detection toward a high-speed brain-computer interface (BCI) speller. METHODS:
      Task-related component analysis (TRCA), which can enhance reproducibility of
      SSVEPs across multiple trials, was employed to improve the signal-to-noise ratio
      (SNR) of SSVEP signals by removing background electroencephalographic (EEG)
      activities. An ensemble method was further developed to integrate TRCA filters
      corresponding to multiple stimulation frequencies. This study conducted a
      comparison of BCI performance between the proposed TRCA-based method and an
      extended canonical correlation analysis (CCA)-based method using a 40-class SSVEP
      dataset recorded from 12 subjects. An online BCI speller was further implemented
      using a cue-guided target selection task with 20 subjects and a free-spelling
      task with 10 of the subjects. RESULTS: The offline comparison results indicate
      that the proposed TRCA-based approach can significantly improve the
      classification accuracy compared with the extended CCA-based method. Furthermore,
      the online BCI speller achieved averaged information transfer rates (ITRs) of
      325.33 +/- 38.17 bits/min with the cue-guided task and 198.67 +/- 50.48 bits/min
      with the free-spelling task. CONCLUSION: This study validated the efficiency of
      the proposed TRCA-based method in implementing a high-speed SSVEP-based BCI.
      SIGNIFICANCE: The high-speed SSVEP-based BCIs using the TRCA method have great
      potential for various applications in communication and control.

PMID- 28436837
TI  - Passive BCI in Operational Environments: Insights, Recent Advances, and Future
      Trends.
AB  - GOAL: This minireview aims to highlight recent important aspects to consider and
      evaluate when passive brain-computer interface (pBCI) systems would be developed
      and used in operational environments, and remarks future directions of their
      applications. METHODS: Electroencephalography (EEG) based pBCI has become an
      important tool for real-time analysis of brain activity since it could
      potentially provide covertly-without distracting the user from the main task-and
      objectively-not affected by the subjective judgment of an observer or the user
      itself-information about the operator cognitive state. RESULTS: Different
      examples of pBCI applications in operational environments and new adaptive
      interface solutions have been presented and described. In addition, a general
      overview regarding the correct use of machine learning techniques (e.g., which
      algorithm to use, common pitfalls to avoid, etc.) in the pBCI field has been
      provided. CONCLUSION: Despite recent innovations on algorithms and
      neurotechnology, pBCI systems are not completely ready to enter the market yet,
      mainly due to limitations of the EEG electrodes technology, and algorithms
      reliability and capability in real settings. SIGNIFICANCE: High complexity and
      safety critical systems (e.g., airplanes, ATM interfaces) should adapt their
      behaviors and functionality accordingly to the user' actual mental state. Thus,
      technologies (i.e., pBCIs) able to measure in real time the user's mental states
      would result very useful in such "high risk" environments to enhance human
      machine interaction, and so increase the overall safety.

PMID- 28436838
TI  - Electromechanical Coupling Factor of Breast Tissue as a Biomarker for Breast
      Cancer.
AB  - GOAL: This research aims to validate a new biomarker of breast cancer by
      introducing electromechanical coupling factor of breast tissue samples as a
      possible additional indicator of breast cancer. Since collagen fibril exhibits a
      structural organization that gives rise to a piezoelectric effect, the difference
      in collagen density between normal and cancerous tissue can be captured by
      identifying the corresponding electromechanical coupling factor. METHODS: The
      design of a portable diagnostic tool and a microelectromechanical systems (MEMS)
      based biochip, which is integrated with a piezoresistive sensing layer for
      measuring the reaction force as well as a microheater for temperature control, is
      introduced. To verify that electromechanical coupling factor can be used as a
      biomarker for breast cancer, the piezoelectric model for breast tissue is
      described with preliminary experimental results on five sets of normal and
      invasive ductal carcinoma (IDC) samples in the 25-45 temperature range.
      CONCLUSION: While the stiffness of breast tissues can be captured as a
      representative mechanical signature which allows one to discriminate among tissue
      types especially in the higher strain region, the electromechanical coupling
      factor shows more distinct differences between the normal and IDC groups over the
      entire strain region than the mechanical signature. From the two-sample -test,
      the electromechanical coupling factor under compression shows statistically
      significant differences ( 0.0039) between the two groups. SIGNIFICANCE: The
      increase in collagen density in breast tissue is an objective and reproducible
      characteristic of breast cancer. Although characterization of mechanical tissue
      property has been shown to be useful for differentiating cancerous tissue from
      normal tissue, using a single parameter may not be sufficient for practical usage
      due to inherent variation among biological samples. The portable breast cancer
      diagnostic tool reported in this manuscript shows the feasibility of measuring
      multiple parameters of breast tissue allowing for practical application.

PMID- 28436840
TI  - A Parametric Computational Model of the Action Potential of Pacemaker Cells.
AB  - OBJECTIVE: A flexible, efficient, and verifiable pacemaker cell model is
      essential to the design of real-time virtual hearts that can be used for closed
      loop validation of cardiac devices. A new parametric model of pacemaker action
      potential is developed to address this need. METHODS: The action potential phases
      are modeled using hybrid automaton with one piecewise-linear continuous variable.
      The model can capture rate-dependent dynamics, such as action potential duration
      restitution, conduction velocity restitution, and overdrive suppression by
      incorporating nonlinear update functions. Simulated dynamics of the model
      compared well with previous models and clinical data. CONCLUSION: The results
      show that the parametric model can reproduce the electrophysiological dynamics of
      a variety of pacemaker cells, such as sinoatrial node, atrioventricular node, and
      the His-Purkinje system, under varying cardiac conditions. SIGNIFICANCE: This is
      an important contribution toward closed-loop validation of cardiac devices using
      real-time heart models.

PMID- 28436839
TI  - Automatic Subretinal Fluid Segmentation of Retinal SD-OCT Images With
      Neurosensory Retinal Detachment Guided by Enface Fundus Imaging.
AB  - OBJECTIVE: Accurate segmentation of neurosensory retinal detachment (NRD)
      associated subretinal fluid in spectral domain optical coherence tomography (SD
      OCT) is vital for the assessment of central serous chorioretinopathy (CSC). A
      novel two-stage segmentation algorithm was proposed, guided by Enface fundus
      imaging. METHODS: In the first stage, Enface fundus image was segmented using
      thickness map prior to detecting the fluid-associated abnormalities with diffuse
      boundaries. In the second stage, the locations of the abnormalities were used to
      restrict the spatial extent of the fluid region, and a fuzzy level set method
      with a spatial smoothness constraint was applied to subretinal fluid segmentation
      in the SD-OCT scans. RESULTS: Experimental results from 31 retinal SD-OCT volumes
      with CSC demonstrate that our method can achieve a true positive volume fraction
      (TPVF), false positive volume fraction (FPVF), and positive predicative value
      (PPV) of 94.3%, 0.97%, and 93.6%, respectively, for NRD regions. Our approach can
      also discriminate NRD-associated subretinal fluid from subretinal pigment
      epithelium fluid associated with pigment epithelial detachment with a TPVF, FPVF,
      and PPV of 93.8%, 0.40%, and 90.5%, respectively. CONCLUSION: We report a fully
      automatic method for the segmentation of subretinal fluid. SIGNIFICANCE: Our
      method shows the potential to improve clinical therapy for CSC.

PMID- 28436841
TI  - Two-Wire Bus Combining Full Duplex Body-Sensor Network and Multilead Biopotential
      Measurements.
AB  - Classical approaches to make high-quality measurements of biopotential signals
      require the use of shielded or multiwire cables connecting the electrodes to a
      central unit in a star arrangement. As a consequence, increasing the number of
      leads increases cabling and connector complexity, which is not only limiting the
      patient comfort but is also anticipated as the main limiting factor to future
      miniaturization and cost reduction of tomorrow's wearables. We have recently
      introduced a novel sensing architecture that significantly reduces the cabling
      complexity by eliminating shielded or multiwire cables and by allowing simple
      connectors, thanks to a bus arrangement. In this architecture, electrodes are
      replaced by so-called cooperative sensors that require synchronous operation for
      systems larger than two sensors. This paper presents a novel full duplex body
      sensor network based on a simple two-wire bus that combines biopotential
      measurements, synchronization, and gathering of data in a single cooperative
      sensor with a throughput up to 2 Mb/s. When compared to others, the suggested
      approach is advantageous as it keeps the cabling complexity at its minimum and
      does not require every sensor to be equipped with wireless communication
      capabilities. First experimental measurements demonstrated the reliability of the
      approach for a wearable 12-lead electrocardiogram monitoring system tested in
      real-life scenario.

PMID- 28436842
TI  - A Hybrid Image Registration and Matching Framework for Real-Time Motion Tracking
      in MRI-Guided Radiotherapy.
AB  - OBJECTIVE: MRI-guided radiotherapy (MRIgRT) is an emerging treatment technique
      where anatomical and pathological structures are imaged through integrated MR
      radiotherapy units. This work aims 1) at assessing the accuracy of optical-flow
      based motion tracking in liver cine-MRI sequences; and 2) at testing a MRIgRT
      workflow combining similarity-based image matching with image registration.
      METHODS: After an initialization stage, a set of template images is collected and
      registered to the first frame of the cine-MRI sequence. Subsequent incoming
      frames are either matched to the most similar template image or registered to the
      first frame when the similarity index is lower than a given threshold. The
      tracking accuracy was evaluated by considering ground-truth liver landmarks
      trajectories, as obtained through the scale-invariant features transform (SIFT).
      RESULTS: Results on a population of 30 liver subjects show that the median
      difference between SIFT- and optical flow-based landmarks trajectories is 1.0 mm,
      i.e., lower than the cine-MRI pixel size (1.28 mm). The computational time of the
      motion tracking workflow (<50 ms) is suitable for real-time motion compensation
      in MRIgRT. Such time could be further reduced to ?30 ms with limited loss of
      accuracy by the combined image matching/registration approach. CONCLUSION: The
      reported workflow allows us to track liver motion with accuracy comparable to
      robust feature matching. Its computational time is suitable for online motion
      monitoring. SIGNIFICANCE: Real-time feedback on the patient anatomy is a crucial
      requirement for the treatment of mobile tumors using advanced motion mitigation
      strategies.

PMID- 28436843
TI  - Fabrication and Performance of a Miniaturized and Integrated Endoscope Ultrasound
      Convex Array for Digestive Tract Imaging.
AB  - OBJECTIVE: this work presents the design, fabrication, and testing of a
      miniaturized and integrated ultrasound endoscope for use as an in situ digestive
      diagnostic device to facilitate real-time ultrasound guidance of intervention
      treatments. METHODS: we designed an optimal structure to integrate an auto-focus
      5-megapixel camera module with an 8-MHz, 64-element curvilinear ultrasonic array
      in one miniaturized package. A novel three-axis auto-focusing voice coil motor
      (VCM) was designed and manufactured for the camera module to move the lens
      position for auto-focusing and to adjust the lens tilt. RESULTS: the results
      showed that the array had a center frequency of 8.09 MHz and a -6-dB fractional
      bandwidth of 83%. At the center frequency, the two-way insertion loss was 40.6
      dB. Endoscopic ultrasound imaging demonstrated satisfactory performance for
      imaging an anthropomorphic phantom of the esophagus. By slightly adjusting the
      tilt angle of the optical axis of the lens, the optical image captured by the
      auto-focusing lens obtained improved definition regardless of changes in the view
      angle of the camera with respect to the objects being captured. CONCLUSION: the
      integrated convex ultrasound endoscope, possessing minimal size, improved optical
      imaging definition, and good ultrasound imaging performance, can become a useful
      tool in digestive tract imaging. SIGNIFICANCE: the miniaturized and integrated
      convex ultrasound endoscope can facilitate real-time ultrasound intervention
      guidance, reducing risks associated with the operation.

PMID- 28436844
TI  - Probabilistic Elastic Part Model: A Pose-Invariant Representation for Real-World
      Face Verification.
AB  - Pose variation remains to be a major challenge for real-world face recognition.
      We approach this problem through a probabilistic elastic part model. We extract
      local descriptors (e.g., LBP or SIFT) from densely sampled multi-scale image
      patches. By augmenting each descriptor with its location, a Gaussian mixture
      model (GMM) is trained to capture the spatial-appearance distribution of the face
      parts of all face images in the training corpus, namely the probabilistic elastic
      part (PEP) model. Each mixture component of the GMM is confined to be a spherical
      Gaussian to balance the influence of the appearance and the location terms, which
      naturally defines a part. Given one or multiple face images of the same subject,
      the PEP-model builds its PEP representation by sequentially concatenating
      descriptors identified by each Gaussian component in a maximum likelihood sense.
      We further propose a joint Bayesian adaptation algorithm to adapt the universally
      trained GMM to better model the pose variations between the target pair of
      faces/face tracks, which consistently improves face verification accuracy. Our
      experiments show that we achieve state-of-the-art face verification accuracy with
      the proposed representations on the Labeled Face in the Wild (LFW) dataset, the
      YouTube video face database, and the CMU MultiPIE dataset.

PMID- 28436845
TI  - Drawing and Recognizing Chinese Characters with Recurrent Neural Network.
AB  - Recent deep learning based approaches have achieved great success on handwriting
      recognition. Chinese characters are among the most widely adopted writing systems
      in the world. Previous research has mainly focused on recognizing handwritten
      Chinese characters. However, recognition is only one aspect for understanding a
      language, another challenging and interesting task is to teach a machine to
      automatically write (pictographic) Chinese characters. In this paper, we propose
      a framework by using the recurrent neural network (RNN) as both a discriminative
      model for recognizing Chinese characters and a generative model for drawing
      (generating) Chinese characters. To recognize Chinese characters, previous
      methods usually adopt the convolutional neural network (CNN) models which require
      transforming the online handwriting trajectory into image-like representations.
      Instead, our RNN based approach is an end-to-end system which directly deals with
      the sequential structure and does not require any domain-specific knowledge. With
      the RNN system (combining an LSTM and GRU), state-of-the-art performance can be
      achieved on the ICDAR-2013 competition database. Furthermore, under the RNN
      framework, a conditional generative model with character embedding is proposed
      for automatically drawing recognizable Chinese characters. The generated
      characters (in vector format) are human-readable and also can be recognized by
      the discriminative RNN model with high accuracy. Experimental results verify the
      effectiveness of using RNNs as both generative and discriminative models for the
      tasks of drawing and recognizing Chinese characters.

PMID- 28436846
TI  - Efficient 2D and 3D Facade Segmentation Using Auto-Context.
AB  - This paper introduces a fast and efficient segmentation technique for 2D images
      and 3D point clouds of building facades. Facades of buildings are highly
      structured and consequently most methods that have been proposed for this problem
      aim to make use of this strong prior information. Contrary to most prior work, we
      are describing a system that is almost domain independent and consists of
      standard segmentation methods. We train a sequence of boosted decision trees
      using auto-context features. This is learned using stacked generalization. We
      find that this technique performs better, or comparable with all previous
      published methods and present empirical results on all available 2D and 3D facade
      benchmark datasets. The proposed method is simple to implement, easy to extend,
      and very efficient at test-time inference.

PMID- 28436847
TI  - Learning Trans-Dimensional Random Fields with Applications to Language Modeling.
AB  - To describe trans-dimensional observations in sample spaces of different
      dimensions, we propose a probabilistic model, called the trans-dimensional random
      field (TRF) by explicitly mixing a collection of random fields. In the framework
      of stochastic approximation (SA), we develop an effective training algorithm,
      called augmented SA, which jointly estimates the model parameters and normalizing
      constants while using trans-dimensional mixture sampling to generate observations
      of different dimensions. Furthermore, we introduce several statistical and
      computational techniques to improve the convergence of the training algorithm and
      reduce computational cost, which together enable us to successfully train TRF
      models on large datasets. The new model and training algorithm are thoroughly
      evaluated in a number of experiments. The word morphology experiment provides a
      benchmark test to study the convergence of the training algorithm and to compare
      with other algorithms, because log-likelihoods and gradients can be exactly
      calculated in this experiment. For language modeling, our experiments demonstrate
      the superiority of the TRF approach in being computationally more efficient in
      computing data probabilities by avoiding local normalization and being able to
      flexibly integrate a richer set of features, when compared with n-gram models and
      neural network models.

PMID- 28436848
TI  - Challenging the Time Complexity of Exact Subgraph Isomorphism for Huge and Dense
      Graphs with VF3.
AB  - Graph matching is essential in several fields that use structured information,
      such as biology, chemistry, social networks, knowledge management, document
      analysis and others. Except for special classes of graphs, graph matching has in
      the worst-case an exponential complexity; however, there are algorithms that show
      an acceptable execution time, as long as the graphs are not too large and not too
      dense. In this paper we introduce a novel subgraph isomorphism algorithm, VF3,
      particularly efficient in the challenging case of graphs with thousands of nodes
      and a high edge density. Its performance, both in terms of time and memory, has
      been assessed on a large dataset of 12,700 random graphs with a size up to 10,000
      nodes, made publicly available. VF3 has been compared with four other state-of
      the-art algorithms, and the huge experimentation required more than two years of
      processing time. The results confirm that VF3 definitely outperforms the other
      algorithms when the graphs become huge and dense, but also has a very good
      performance on smaller or sparser graphs.

PMID- 28436849
TI  - Reverse Classification Accuracy: Predicting Segmentation Performance in the
      Absence of Ground Truth.
AB  - When integrating computational tools, such as automatic segmentation, into
      clinical practice, it is of utmost importance to be able to assess the level of
      accuracy on new data and, in particular, to detect when an automatic method
      fails. However, this is difficult to achieve due to the absence of ground truth.
      Segmentation accuracy on clinical data might be different from what is found
      through cross validation, because validation data are often used during
      incremental method development, which can lead to overfitting and unrealistic
      performance expectations. Before deployment, performance is quantified using
      different metrics, for which the predicted segmentation is compared with a
      reference segmentation, often obtained manually by an expert. But little is known
      about the real performance after deployment when a reference is unavailable. In
      this paper, we introduce the concept of reverse classification accuracy (RCA) as
      a framework for predicting the performance of a segmentation method on new data.
      In RCA, we take the predicted segmentation from a new image to train a reverse
      classifier, which is evaluated on a set of reference images with available ground
      truth. The hypothesis is that if the predicted segmentation is of good quality,
      then the reverse classifier will perform well on at least some of the reference
      images. We validate our approach on multi-organ segmentation with different
      classifiers and segmentation methods. Our results indicate that it is indeed
      possible to predict the quality of individual segmentations, in the absence of
      ground truth. Thus, RCA is ideal for integration into automatic processing
      pipelines in clinical routine and as a part of large-scale image analysis
      studies.

PMID- 28436850
TI  - Pulmonary Lobe Segmentation With Probabilistic Segmentation of the Fissures and a
      Groupwise Fissure Prior.
AB  - A fully automated, unsupervised lobe segmentation algorithm is presented based on
      a probabilistic segmentation of the fissures and the simultaneous construction of
      a populationmodel of the fissures. A two-class probabilistic segmentation
      segments the lung into candidate fissure voxels and the surrounding parenchyma.
      This was combined with anatomical information and a groupwise fissure prior to
      drive non-parametric surface fitting to obtain the final segmentation. The
      performance of our fissure segmentation was validated on 30 patients from the
      chronic obstructive pulmonary disease COPDGene cohort, achieving a high median F1
      -score of 0.90 and showed general insensitivity to filter parameters. We
      evaluated our lobe segmentation algorithm on the Lobe and Lung Analysis 2011
      dataset, which contains 55 cases at varying levels of pathology. We achieved the
      highest score of 0.884 of the automated algorithms. Our method was further tested
      quantitatively and qualitatively on 80 patients from the COPDgene study at
      varying levels of functional impairment. Accurate segmentation of the lobes is
      shown at various degrees of fissure incompleteness for 96% of all cases. We also
      show the utility of including a groupwise prior in segmenting the lobes in
      regions of grossly incomplete fissures.

PMID- 28436851
TI  - Synergistic PET and SENSE MR Image Reconstruction Using Joint Sparsity
      Regularization.
AB  - In this paper, we propose a generalized joint sparsity regularization prior and
      reconstruction framework for the synergistic reconstruction of positron emission
      tomography (PET) and under sampled sensitivity encoded magnetic resonance imaging
      data with the aim of improving image quality beyond that obtained through
      conventional independent reconstructions. The proposed prior improves upon the
      joint total variation (TV) using a non-convex potential function that assigns a
      relatively lower penalty for the PET and MR gradients, whose magnitudes are
      jointly large, thus permitting the preservation and formation of common
      boundaries irrespective of their relative orientation. The alternating direction
      method of multipliers (ADMM) optimization framework was exploited for the joint
      PET-MR image reconstruction. In this framework, the joint maximum a posteriori
      objective function was effectively optimized by alternating between well
      established regularized PET and MR image reconstructions. Moreover, the
      dependency of the joint prior on the PET and MR signal intensities was addressed
      by a novel alternating scaling of the distribution of the gradient vectors. The
      proposed prior was compared with the separate TV and joint TV regularization
      methods using extensive simulation and real clinical data. In addition, the
      proposed joint prior was compared with the recently proposed linear parallel
      level sets (PLSs) method using a benchmark simulation data set. Our simulation
      and clinical data results demonstrated the improved quality of the
      synergistically reconstructed PET-MR images compared with the unregularized and
      conventional separately regularized methods. It was also found that the proposed
      prior can outperform both the joint TV and linear PLS regularization methods in
      assisting edge preservation and recovery of details, which are otherwise impaired
      by noise and aliasing artifacts. In conclusion, the proposed joint sparsity
      regularization within the presented a ADMM reconstruction framework is a
      promising technique, nonetheless our clinical results showed that the clinical
      applicability of joint reconstruction might be limited in current PET-MR
      scanners, mainly due to the lower resolution of PET images.

PMID- 28436853
TI  - Automatic Skin Lesion Segmentation Using Deep Fully Convolutional Networks With
      Jaccard Distance.
AB  - Automatic skin lesion segmentation in dermoscopic images is a challenging task
      due to the low contrast between lesion and the surrounding skin, the irregular
      and fuzzy lesion borders, the existence of various artifacts, and various imaging
      acquisition conditions. In this paper, we present a fully automatic method for
      skin lesion segmentation by leveraging 19-layer deep convolutional neural
      networks that is trained end-to-end and does not rely on prior knowledge of the
      data. We propose a set of strategies to ensure effective and efficient learning
      with limited training data. Furthermore, we design a novel loss function based on
      Jaccard distance to eliminate the need of sample re-weighting, a typical
      procedure when using cross entropy as the loss function for image segmentation
      due to the strong imbalance between the number of foreground and background
      pixels. We evaluated the effectiveness, efficiency, as well as the generalization
      capability of the proposed framework on two publicly available databases. One is
      from ISBI 2016 skin lesion analysis towards melanoma detection challenge, and the
      other is the PH2 database. Experimental results showed that the proposed method
      outperformed other state-of-the-art algorithms on these two databases. Our method
      is general enough and only needs minimum pre- and post-processing, which allows
      its adoption in a variety of medical image segmentation tasks.

PMID- 28436852
TI  - Frequency-Selective Computed Tomography: Applications During Periodic Thoracic
      Motion.
AB  - We seek to use computed tomography (CT) to characterize regional lung parenchymal
      deformation during high-frequency and multi-frequency oscillatory ventilation.
      Periodic motion of thoracic structures results in artifacts of CT images obtained
      by standard reconstruction algorithms, especially for frequencies exceeding that
      of the X-ray source rotation. In this paper, we propose an acquisition and
      reconstruction technique for high-resolution imaging of the thorax during
      periodic motion. Our technique relies on phase-binning projections according to
      the frequency of subject motion relative to the scanner rotation, prior to
      volumetric reconstruction. The mathematical theory and limitations of the
      proposed technique are presented, and then validated in a simulated phantom as
      well as a living porcine subject during oscillatory ventilation. The 4-D image
      sequences obtained using this frequency-selective reconstruction technique
      yielded high-spatio-temporal resolution of the thorax during periodic motion. We
      conclude that the frequency-based selection of CT projections is ideal for
      characterizing dynamic deformations of thoracic structures that are ordinarily
      obscured by motion artifact using conventional reconstruction techniques.

PMID- 28436854
TI  - Manifold Embedding and Semantic Segmentation for Intraoperative Guidance With
      Hyperspectral Brain Imaging.
AB  - Recent advances in hyperspectral imaging have made it a promising solution for
      intra-operative tissue characterization, with the advantages of being non
      contact, non-ionizing, and non-invasive. Working with hyperspectral images in
      vivo, however, is not straightforward as the high dimensionality of the data
      makes real-time processing challenging. In this paper, a novel dimensionality
      reduction scheme and a new processing pipeline are introduced to obtain a
      detailed tumor classification map for intra-operative margin definition during
      brain surgery. However, existing approaches to dimensionality reduction based on
      manifold embedding can be time consuming and may not guarantee a consistent
      result, thus hindering final tissue classification. The proposed framework aims
      to overcome these problems through a process divided into two steps:
      dimensionality reduction based on an extension of the T-distributed stochastic
      neighbor approach is first performed and then a semantic segmentation technique
      is applied to the embedded results by using a Semantic Texton Forest for tissue
      classification. Detailed in vivo validation of the proposed method has been
      performed to demonstrate the potential clinical value of the system.

PMID- 28436855
TI  - Real-Time Implementation of Calderon's Method on Subject-Specific Domains.
AB  - A real-time implementation of Calderon's method for the reconstruction of a 2-D
      conductivity from electrical impedance tomography data is presented, in which
      domain-specific modeling is taken into account. This is the first implementation
      of Calderon's method that accounts for correct modeling of non-symmetric domain
      boundaries in image reconstruction. The domain-specific Calderon's method is
      derived and reconstructions from experimental tank data are presented,
      quantifying the distortion when correct modeling is not included in the
      reconstruction algorithm. Reconstructions from human subject volunteers are
      presented, demonstrating the method's effectiveness for imaging changes due to
      ventilation and perfusion in the human thorax.

PMID- 28436856
TI  - Task-Based Modeling of a 5k Ultra-High-Resolution Medical Imaging System for
      Digital Breast Tomosynthesis.
AB  - High-resolution, low-noise X-ray detectors based on CMOS active pixel sensor
      (APS) technology have demonstrated superior imaging performance for digital
      breast tomosynthesis (DBT). This paper presents a task-based model for a high
      resolution medical imaging system to evaluate its ability to detect simulated
      microcalcifications and masses as lesions for breast cancer. A 3-D cascaded
      system analysis for a 50- [Formula: see text] pixel pitch CMOS APS X-ray detector
      was integrated with an object task function, a medical imaging display model, and
      the human eye contrast sensitivity function to calculate the detectability index
      and area under the ROC curve (AUC). It was demonstrated that the display pixel
      pitch and zoom factor should be optimized to improve the AUC for detecting small
      microcalcifications. In addition, detector electronic noise of smaller than 300 e
      and a high display maximum luminance (>1000 cd/cm 2) are desirable to
      distinguish microcalcifications of [Formula: see text] in size. For low contrast
      mass detection, a medical imaging display with a minimum of 12-bit gray levels is
      recommended to realize accurate luminance levels. A wide projection angle range
      of greater than +/-30 degrees  in combination with the image gray level
      magnification could improve the mass detectability especially when the anatomical
      background noise is high. On the other hand, a narrower projection angle range
      below +/-20 degrees  can improve the small, high contrast object detection. Due
      to the low mass contrast and luminance, the ambient luminance should be
      controlled below 5 cd/ [Formula: see text]. Task-based modeling provides
      important firsthand imaging performance of the high-resolution CMOS-based medical
      imaging system that is still at early stage development for DBT. The modeling
      results could guide the prototype design and clinical studies in the future.

PMID- 28436857
TI  - Real-time Triple-modal Photoacoustic, Ultrasound, and Magnetic Resonance Fusion
      Imaging of Humans.
AB  - Imaging that fuses multiple modes has become a useful tool for diagnosis and
      therapeutic monitoring. As a next step, real-time fusion imaging has attracted
      interest as for a tool to guide surgery. One widespread fusion imaging technique
      in surgery combines real-time ultrasound (US) imaging and pre-acquired magnetic
      resonance (MR) imaging. However, US imaging visualizes only structural
      information with relatively low contrast. Here, we present a photoacoustic (PA),
      US, and MR fusion imaging system which integrates a clinical PA and US imaging
      system with an optical tracking-based navigation sub-system. Through co
      registration of pre-acquired MR and real-time PA/US images, overlaid PA, US, and
      MR images can be concurrently displayed in real time. We successfully acquired
      fusion images from a phantom and a blood vessel in a human forearm. This fusion
      imaging can complementarily delineate the morphological and vascular structure of
      tissues with good contrast and sensitivity, has a well-established user
      interface, and can be flexibly integrated with clinical environments. As a novel
      fusion imaging, the proposed triple-mode imaging can provide comprehensive image
      guidance in real time, and can potentially assist various surgeries.

PMID- 28436859
TI  - In Vivo Intracardiac Vector Flow Imaging Using Phased Array Transducers for
      Pediatric Cardiology.
AB  - Two-dimensional blood speckle tracking (ST) has shown promise for measuring
      complex flow patterns in neonatal hearts using linear arrays and high-frame-rate
      plane wave imaging. For general pediatric applications, however, the need for
      phased array probes emerges due to the limited intercostal acoustic window
      available. In this paper, a clinically approved real-time duplex imaging setup
      with phased array probes was used to investigate the potential of blood ST for
      the 2-D vector flow imaging of children with congenital heart disease. To
      investigate transmit beam pattern and tracking accuracy, straight tubes with
      parabolic flow were simulated at three depths (4.5, 7, and 9.5 cm). Due to the
      small aperture available, diffraction effects could be observed when approaching
      10 cm, which limited the number of parallel receive beams that could be utilized.
      Moving to (slightly) diverging beams was shown to solve this issue at the expense
      of a loss in signal-to-noise ratio. To achieve consistent estimates, a forward
      backward tracking scheme was introduced to avoid measurement bias occurring due
      to tracking kernel averaging artifacts at flow domain boundaries. Promising
      results were observed for depths <10 cm in two pediatric patients, where complex
      cardiac flow patterns could be estimated and visualized. As a loss in penetration
      compared with color flow imaging is expected, a larger clinical study is needed
      to establish the clinical feasibility of this approach.

PMID- 28436858
TI  - A Spectral CT Method to Directly Estimate Basis Material Maps From Experimental
      Photon-Counting Data.
AB  - The proposed spectral CT method solves the constrained one-step spectral CT
      reconstruction (cOSSCIR) optimization problem to estimate basis material maps
      while modeling the nonlinear X-ray detection process and enforcing convex
      constraints on the basis map images. In order to apply the optimization-based
      reconstruction approach to experimental data, the presented method empirically
      estimates the effective energy-window spectra using a calibration procedure. The
      amplitudes of the estimated spectra were further optimized as part of the
      reconstruction process to reduce ring artifacts. A validation approach was
      developed to select constraint parameters. The proposed spectral CT method was
      evaluated through simulations and experiments with a photon-counting detector.
      Basis material map images were successfully reconstructed using the presented
      empirical spectral modeling and cOSSCIR optimization approach. In simulations,
      the cOSSCIR approach accurately reconstructed the basis map images (<1% error).
      In experiments, the proposed method estimated the low-density polyethylene region
      of the basis maps with 0.5% error in the PMMA image and 4% error in the aluminum
      image. For the Teflon region, the experimental results demonstrated 8% and 31%
      error in the PMMA and aluminum basis material maps, respectively, compared with 
      24% and 126% error without estimation of the effective energy window spectra,
      with residual errors likely due to insufficient modeling of detector effects. The
      cOSSCIR algorithm estimated the material decomposition angle to within 1.3 degree
      error, where, for reference, the difference in angle between PMMA and muscle
      tissue is 2.1 degrees. The joint estimation of spectral-response scaling
      coefficients and basis material maps was found to reduce ring artifacts in both a
      phantom and tissue specimen. The presented validation procedure demonstrated
      feasibility for the automated determination of algorithm constraint parameters.

PMID- 28436860
TI  - Effect on High-Intensity Fields of a Tough Hydrophone With Hydrothermal PZT Thick
      Film Vibrator and Titanium Front Layer.
AB  - A novel tough hydrophone was fabricated by depositing hydrothermally synthesized
      lead zirconate titanate polycrystalline film on the back-side surface of a
      titanium plate. Our developed tough hydrophone resisted damage in a high-pressure
      field (15 MPa) at a focal point of a sinusoidal continuous wave driven by a
      concave high-intensity focused ultrasound (HIFU) transducer with up to 50 W of
      power input to the sound source. The hydrophone was suitable for the HIFU field,
      even though the hydrophone has a flat-shape tip of 3.5 mm diameter, which is
      slightly larger than the wavelength of a few megahertz. In this paper,
      experiments are performed to assess the effect on the HIFU field of changing the
      shape of the tough hydrophone, with the aim of developing a tough hydrophone. The
      spatial distribution of the acoustic bubbles around the focal point was
      visualized by using ultrasonic diagnostic equipment with the tough hydrophone
      located at the focal point of the HIFU transducer. From the visualization, the
      trapped acoustic bubbles were seen to arise from the standing wave, which implies
      that the acoustic pressure is reduced by this cloud of acoustic bubbles that
      appeared during hydrophone measurement. Although cavitation and acoustic bubbles
      may be unavoidable when using high-intensity ultrasound, the estimated result of
      evaluating acoustic fields without misunderstanding by acoustic bubbles can be
      obtained by the aid of visualizing bubbles around the tough hydrophone.

PMID- 28436861
TI  - Uncorrelated Component Analysis-Based Hashing.
AB  - The approximate nearest neighbor (ANN) search problem is important in
      applications such as information retrieval. Several hashing-based search methods
      that provide effective solutions to the ANN search problem have been proposed.
      However, most of these focus on similarity preservation and coding error
      minimization, and pay little attention to optimizing the precision-recall curve
      or receiver operating characteristic curve. In this paper, we propose a novel
      projection-based hashing method that attempts to maximize precision and recall.
      We first introduce an uncorrelated component analysis (UCA) transformation by
      examining precision and recall, and then propose a UCA-based hashing method. The
      proposed method is evaluated with a variety of data sets. The results show that
      UCA-based hashing outperforms state-of-the-art methods, and has computationally
      efficient training and encoding processes.

PMID- 28436862
TI  - Part-Based Deep Hashing for Large-Scale Person Re-Identification.
AB  - Large-scale is a trend in person re-identi- fication (re-id). It is important
      that real-time search be performed in a large gallery. While previous methods
      mostly focus on discriminative learning, this paper makes the attempt in
      integrating deep learning and hashing into one framework to evaluate the
      efficiency and accuracy for large-scale person re-id. We integrate spatial
      information for discriminative visual representation by partitioning the
      pedestrian image into horizontal parts. Specifically, Part-based Deep Hashing
      (PDH) is proposed, in which batches of triplet samples are employed as the input
      of the deep hashing architecture. Each triplet sample contains two pedestrian
      images (or parts) with the same identity and one pedestrian image (or part) of
      the different identity. A triplet loss function is employed with a constraint
      that the Hamming distance of pedestrian images (or parts) with the same identity
      is smaller than ones with the different identity. In the experiment, we show that
      the proposed PDH method yields very competitive re-id accuracy on the large-scale
      Market-1501 and Market-1501+500K datasets.

PMID- 28436863
TI  - Optimization of Camera Arrangement Using Correspondence Field to Improve Depth
      Estimation.
AB  - Stereo matching algorithms attempt to estimate depth from the images obtained by
      two cameras. In most cases, the arrangement of cameras (their locations and
      orientations with respect to the scene) is determined based on human experience.
      In this paper, it is shown that the camera arrangement can be optimized using the
      concept of correspondence field (CF) for better acquisition of depth.
      Specifically, this paper demonstrates the relationship between the CF of a pair
      of cameras and depth estimation accuracy and presents a method to optimize their
      arrangement based on the gradient of the CF. The experimental results show that a
      pair of cameras optimized by the proposed method can improve the accuracy of
      depth estimation by as much as 30% compared with the conventional camera
      arrangements.

PMID- 28436864
TI  - Tracking Based Multi-Orientation Scene Text Detection: A Unified Framework With
      Dynamic Programming.
AB  - There are a variety of grand challenges for multi-orientation text detection in
      scene videos, where the typical issues include skew distortion, low contrast, and
      arbitrary motion. Most conventional video text detection methods using individual
      frames have limited performance. In this paper, we propose a novel tracking based
      multi-orientation scene text detection method using multiple frames within a
      unified framework via dynamic programming. First, a multi-information fusion
      based multi-orientation text detection method in each frame is proposed to
      extensively locate possible character candidates and extract text regions with
      multiple channels and scales. Second, an optimal tracking trajectory is learned
      and linked globally over consecutive frames by dynamic programming to finally
      refine the detection results with all detection, recognition, and prediction
      information. Moreover, the effectiveness of our proposed system is evaluated with
      the state-of-the-art performances on several public data sets of multi
      orientation scene text images and videos, including MSRA-TD500, USTB-SV1K, and
      ICDAR 2015 Scene Videos.

PMID- 28436865
TI  - Video Anomaly Detection With Compact Feature Sets for Online Performance.
AB  - Over the past decade, video anomaly detection has been explored with remarkable
      results. However, research on methodologies suitable for online performance is
      still very limited. In this paper, we present an online framework for video
      anomaly detection. The key aspect of our framework is a compact set of highly
      descriptive features, which is extracted from a novel cell structure that helps
      to define support regions in a coarse-to-fine fashion. Based on the scene's
      activity, only a limited number of support regions are processed, thus limiting
      the size of the feature set. Specifically, we use foreground occupancy and
      optical flow features. The framework uses an inference mechanism that evaluates
      the compact feature set via Gaussian Mixture Models, Markov Chains, and Bag-of
      Words in order to detect abnormal events. Our framework also considers the joint
      response of the models in the local spatio-temporal neighborhood to increase
      detection accuracy. We test our framework on popular existing data sets and on a
      new data set comprising a wide variety of realistic videos captured by
      surveillance cameras. This particular data set includes surveillance videos
      depicting criminal activities, car accidents, and other dangerous situations.
      Evaluation results show that our framework outperforms other online methods and
      attains a very competitive detection performance compared with state-of-the-art
      non-online methods.

PMID- 28436866
TI  - Universal Multimode Background Subtraction.
AB  - In this paper, we present a complete change detection system named multimode
      background subtraction. The universal nature of system allows it to robustly
      handle multitude of challenges associated with video change detection, such as
      illumination changes, dynamic background, camera jitter, and moving camera. The
      system comprises multiple innovative mechanisms in background modeling, model
      update, pixel classification, and the use of multiple color spaces. The system
      first creates multiple background models of the scene followed by an initial
      foreground/background probability estimation for each pixel. Next, the image
      pixels are merged together to form mega-pixels, which are used to spatially
      denoise the initial probability estimates to generate binary masks for both RGB
      and YCbCr color spaces. The masks generated after processing these input images
      are then combined to separate foreground pixels from the background.
      Comprehensive evaluation of the proposed approach on publicly available test
      sequences from the CDnet and the ESI data sets shows superiority in the
      performance of our system over other state-of-the-art algorithms.

PMID- 28436867
TI  - RSCM: Region Selection and Concurrency Model for Multi-Class Weather Recognition.
AB  - Toward weather condition recognition, we emphasize the importance of regional
      cues in this paper and address a few important problems regarding appropriate
      representation, its differentiation among regions, and weather-condition feature
      construction. Our major contribution is, first, to construct a multi-class
      benchmark data set containing 65 000 images from six common categories for sunny,
      cloudy, rainy, snowy, haze, and thunder weather. This data set also benefits
      weather classification and attribute recognition. Second, we propose a deep
      learning framework named region selection and concurrency model (RSCM) to help
      discover regional properties and concurrency. We evaluate RSCM on our multi-class
      benchmark data and another public data set for weather recognition.

PMID- 28436868
TI  - High-Order Local Pooling and Encoding Gaussians Over a Dictionary of Gaussians.
AB  - Local pooling (LP) in configuration (feature) space proposed by Boureau et al.
      explicitly restricts similar features to be aggregated, which can preserve as
      much discriminative information as possible. At the time it appeared, this method
      combined with sparse coding achieved competitive classification results with only
      a small dictionary. However, its performance lags far behind the state-of-the-art
      results as only the zero-order information is exploited. Inspired by the success
      of high-order statistical information in existing advanced feature coding or
      pooling methods, we make an attempt to address the limitation of LP. To this end,
      we present a novel method called high-order LP (HO-LP) to leverage the
      information higher than the zero-order one. Our idea is intuitively simple: we
      compute the first- and second-order statistics per configuration bin and model
      them as a Gaussian. Accordingly, we employ a collection of Gaussians as visual
      words to represent the universal probability distribution of features from all
      classes. Our problem is naturally formulated as encoding Gaussians over a
      dictionary of Gaussians as visual words. This problem, however, is challenging
      since the space of Gaussians is not a Euclidean space but forms a Riemannian
      manifold. We address this challenge by mapping Gaussians into the Euclidean
      space, which enables us to perform coding with common Euclidean operations rather
      than complex and often expensive Riemannian operations. Our HO-LP preserves the
      advantages of the original LP: pooling only similar features and using a small
      dictionary. Meanwhile, it achieves very promising performance on standard
      benchmarks, with either conventional, hand-engineered features or deep learning
      based features.

PMID- 28436869
TI  - Establishing Keypoint Matches on Multimodal Images With Bootstrap Strategy and
      Global Information.
AB  - This paper proposes an algorithm of building keypoint matches on multimodal
      images by combining a bootstrap process and global information. The correct ratio
      of keypoint matches built with descriptors is typically very low on multimodal
      images of large spectral difference. To identify correct matches, global
      information is utilized for evaluating keypoint matches and a bootstrap technique
      is employed to reduce the computational cost. A keypoint match determines a
      transformation T and a similarity metric between the reference and the
      transformed test image by T. The similarity metric encodes global information
      over entire images, and hence, a higher similarity indicates the match can bring
      more image content into alignment, implying it tends to be correct.
      Unfortunately, exhausting triplets/quadruples of matches for affine/projective
      transformation is computationally intractable, when the number of keypoints is
      large. To reduce the computational cost, a bootstrap technique is employed that
      starts from single matches for a translation and rotation model, and goes
      increasingly to quadruples of four matches for a projective model. The global
      information screens for "good" matches at each stage and the bootstrap strategy
      makes the screening process computationally feasible. Experimental results show
      that the proposed method can establish reliable keypoint matches on challenging
      multimodal images of strong multimodality.

PMID- 28436870
TI  - A General Framework for Edited Video and Raw Video Summarization.
AB  - In this paper, we build a general summarization framework for both of edited
      video and raw video summarization. Overall, our work can be divided into three
      folds. 1) Four models are designed to capture the properties of video summaries,
      i.e., containing important people and objects (importance), representative to the
      video content (representativeness), no similar key-shots (diversity), and
      smoothness of the storyline (storyness). Specifically, these models are
      applicable to both edited videos and raw videos. 2) A comprehensive score
      function is built with the weighted combination of the aforementioned four
      models. Note that the weights of the four models in the score function, denoted
      as property-weight, are learned in a supervised manner. Besides, the property
      weights are learned for edited videos and raw videos, respectively. 3) The
      training set is constructed with both edited videos and raw videos in order to
      make up the lack of training data. Particularly, each training video is equipped
      with a pair of mixing-coefficients, which can reduce the structure mess in the
      training set caused by the rough mixture. We test our framework on three data
      sets, including edited videos, short raw videos, and long raw videos.
      Experimental results have verified the effectiveness of the proposed framework.

PMID- 28436871
TI  - A Systematic Approach for Cross-Source Point Cloud Registration by Preserving
      Macro and Micro Structures.
AB  - We propose a systematic approach for registering cross-source point clouds that
      come from different kinds of sensors. This task is especially challenging due to
      the presence of significant missing data, large variations in point density,
      scale difference, large proportion of noise, and outliers. The robustness of the
      method is attributed to the extraction of macro and micro structures. Macro
      structure is the overall structure that maintains similar geometric layout in
      cross-source point clouds. Micro structure is the element (e.g., local segment)
      being used to build the macro structure. We use graph to organize these
      structures and convert the registration into graph matching. With a novel
      proposed descriptor, we conduct the graph matching in a discriminative feature
      space. The graph matching problem is solved by an improved graph matching
      solution, which considers global geometrical constraints. Robust cross source
      registration results are obtained by incorporating graph matching outcome with
      RANSAC and ICP refinements. Compared with eight state-of-the-art registration
      algorithms, the proposed method invariably outperforms on Pisa Cathedral and
      other challenging cases. In order to compare quantitatively, we propose two
      challenging cross-source data sets and conduct comparative experiments on more
      than 27 cases, and the results show we obtain much better performance than other
      methods. The proposed method also shows high accuracy in same-source data sets.

PMID- 28436872
TI  - Hash Bit Selection for Nearest Neighbor Search.
AB  - To overcome the barrier of storage and computation when dealing with gigantic
      scale data sets, compact hashing has been studied extensively to approximate the
      nearest neighbor search. Despite the recent advances, critical design issues
      remain open in how to select the right features, hashing algorithms, and/or
      parameter settings. In this paper, we address these by posing an optimal hash bit
      selection problem, in which an optimal subset of hash bits are selected from a
      pool of candidate bits generated by different features, algorithms, or
      parameters. Inspired by the optimization criteria used in existing hashing
      algorithms, we adopt the bit reliability and their complementarity as the
      selection criteria that can be carefully tailored for hashing performance in
      different tasks. Then, the bit selection solution is discovered by finding the
      best tradeoff between search accuracy and time using a modified dynamic
      programming method. To further reduce the computational complexity, we employ the
      pairwise relationship among hash bits to approximate the high-order independence
      property, and formulate it as an efficient quadratic programming method that is
      theoretically equivalent to the normalized dominant set problem in a vertex- and
      edge-weighted graph. Extensive large-scale experiments have been conducted under
      several important application scenarios of hash techniques, where our bit
      selection framework can achieve superior performance over both the naive
      selection methods and the state-of-the-art hashing algorithms, with significant
      accuracy gains ranging from 10% to 50%, relatively.

PMID- 28436873
TI  - Predicting the Quality of Fused Long Wave Infrared and Visible Light Images.
AB  - The capability to automatically evaluate the quality of long wave infrared (LWIR)
      and visible light images has the potential to play an important role in
      determining and controlling the quality of a resulting fused LWIR-visible light
      image. Extensive work has been conducted on studying the statistics of natural
      LWIR and visible images. Nonetheless, there has been little work done on
      analyzing the statistics of fused LWIR and visible images and associated
      distortions. In this paper, we analyze five multi-resolution-based image fusion
      methods in regards to several common distortions, including blur, white noise,
      JPEG compression, and non-uniformity. We study the natural scene statistics of
      fused images and how they are affected by these kinds of distortions.
      Furthermore, we conducted a human study on the subjective quality of pristine and
      degraded fused LWIR-visible images. We used this new database to create an
      automatic opinion-distortion-unaware fused image quality model and analyzer
      algorithm. In the human study, 27 subjects evaluated 750 images over five
      sessions each. We also propose an opinion-aware fused image quality analyzer,
      whose relative predictions with respect to other state-of-the-art models
      correlate better with human perceptual evaluations than competing methods. An
      implementation of the proposed fused image quality measures can be found at
      https://github.com/ujemd/NSS-of-LWIR-and-Vissible-Images. Also, the new database
      can be found at http://bit.ly/2noZlbQ.

PMID- 28436874
TI  - Track Everything: Limiting Prior Knowledge in Online Multi-Object Recognition.
AB  - This paper addresses the problem of online tracking and classification of
      multiple objects in an image sequence. Our proposed solution is to first track
      all objects in the scene without relying on object-specific prior knowledge,
      which in other systems can take the form of hand-crafted features or user-based
      track initialization. We then classify the tracked objects with a fast-learning
      image classifier, that is based on a shallow convolutional neural network
      architecture and demonstrate that object recognition improves when this is
      combined with object state information from the tracking algorithm. We argue that
      by transferring the use of prior knowledge from the detection and tracking stages
      to the classification stage, we can design a robust, general purpose object
      recognition system with the ability to detect and track a variety of object
      types. We describe our biologically inspired implementation, which adaptively
      learns the shape and motion of tracked objects, and apply it to the Neovision2
      Tower benchmark data set, which contains multiple object types. An experimental
      evaluation demonstrates that our approach is competitive with the state-of-the
      art video object recognition systems that do make use of object-specific prior
      knowledge in detection and tracking, while providing additional practical
      advantages by virtue of its generality.

PMID- 28436875
TI  - Zero-Shot Learning With Transferred Samples.
AB  - By transferring knowledge from the abundant labeled samples of known source
      classes, zero-shot learning (ZSL) makes it possible to train recognition models
      for novel target classes that have no labeled samples. Conventional ZSL
      approaches usually adopt a two-step recognition strategy, in which the test
      sample is projected into an intermediary space in the first step, and then the
      recognition is carried out by considering the similarity between the sample and
      target classes in the intermediary space. Due to this redundant intermediate
      transformation, information loss is unavoidable, thus degrading the performance
      of overall system. Rather than adopting this two-step strategy, in this paper, we
      propose a novel one-step recognition framework that is able to perform
      recognition in the original feature space by using directly trained classifiers.
      To address the lack of labeled samples for training supervised classifiers for
      the target classes, we propose to transfer samples from source classes with
      pseudo labels assigned, in which the transferred samples are selected based on
      their transferability and diversity. Moreover, to account for the unreliability
      of pseudo labels of transferred samples, we modify the standard support vector
      machine formulation such that the unreliable positive samples can be recognized
      and suppressed in the training phase. The entire framework is fairly general with
      the possibility of further extensions to several common ZSL settings. Extensive
      experiments on four benchmark data sets demonstrate the superiority of the
      proposed framework, compared with the state-of-the-art approaches, in various
      settings.

PMID- 28436876
TI  - Deeply Learned View-Invariant Features for Cross-View Action Recognition.
AB  - Classifying human actions from varied views is challenging due to huge data
      variations in different views. The key to this problem is to learn discriminative
      view-invariant features robust to view variations. In this paper, we address this
      problem by learning view-specific and view-shared features using novel deep
      models. View-specific features capture unique dynamics of each view while view
      shared features encode common patterns across views. A novel sample-affinity
      matrix is introduced in learning shared features, which accurately balances
      information transfer within the samples from multiple views and limits the
      transfer across samples. This allows us to learn more discriminative shared
      features robust to view variations. In addition, the incoherence between the two
      types of features is encouraged to reduce information redundancy and exploit
      discriminative information in them separately. The discriminative power of the
      learned features is further improved by encouraging features in the same
      categories to be geometrically closer. Robust view-invariant features are finally
      learned by stacking several layers of features. Experimental results on three
      multi-view data sets show that our approaches outperform the state-of-the-art
      approaches.

PMID- 28436877
TI  - Packing Vertex Data into Hardware-Decompressible Textures.
AB  - Most graphics hardware features memory to store textures and vertex data for
      rendering. However, because of the irreversible trend of increasing complexity of
      scenes, rendering a scene can easily reach the limit of memory resources. Thus,
      vertex data are preferably compressed, with a requirement that they can be
      decompressed during rendering. In this paper, we present a novel method to
      exploit existing hardware texture compression circuits to facilitate the
      decompression of vertex data in graphics processing unit (GPUs). This built-in
      hardware allows real-time, random-order decoding of data. However, vertex data
      must be packed into textures, and careless packing arrangements can easily
      disrupt data coherence. Hence, we propose an optimization approach for the best
      vertex data permutation that minimizes compression error. All of these result in
      fast and high-quality vertex data decompression for real-time rendering. To
      further improve the visual quality, we introduce vertex clustering to reduce the
      dynamic range of data during quantization. Our experiments demonstrate the
      effectiveness of our method for various vertex data of 3D models during rendering
      with the advantages of a minimized memory footprint and high frame rate.

PMID- 28436879
TI  - Study on Interaction Between Temporal and Spatial Information in Classification
      of EMG Signals for Myoelectric Prostheses.
AB  - Advanced forearm prosthetic devices employ classifiers to recognize different
      electromyography (EMG) signal patterns, in order to identify the user's intended
      motion gesture. The classification accuracy is one of the main determinants of
      real-time controllability of a prosthetic limb and hence the necessity to achieve
      as high an accuracy as possible. In this paper, we study the effects of the
      temporal and spatial information provided to the classifier on its off-line
      performance and analyze their inter-dependencies. EMG data associated with seven
      practical hand gestures were recorded from partial-hand and trans-radial amputee
      volunteers as well as able-bodied volunteers. An extensive investigation was
      conducted to study the effect of analysis window length, window overlap, and the
      number of electrode channels on the classification accuracy as well as their
      interactions. Our main discoveries are that the effect of analysis window length
      on classification accuracy is practically independent of the number of electrodes
      for all participant groups; window overlap has no direct influence on classifier
      performance, irrespective of the window length, number of channels, or limb
      condition; the type of limb deficiency and the existing channel count influence
      the reduction in classification error achieved by adding more number of channels;
      partial-hand amputees outperform trans-radial amputees, with classification
      accuracies of only 11.3% below values achieved by able-bodied volunteers.

PMID- 28436880
TI  - A Human-Robot Co-Manipulation Approach Based on Human Sensorimotor Information.
AB  - This paper aims to improve the interaction and coordination between the human and
      the robot in cooperative execution of complex, powerful, and dynamic tasks. We
      propose a novel approach that integrates online information about the human motor
      function and manipulability properties into the hybrid controller of the
      assistive robot. Through this human-in-the-loop framework, the robot can adapt to
      the human motor behavior and provide the appropriate assistive response in
      different phases of the cooperative task. We experimentally evaluate the proposed
      approach in two human-robot co-manipulation tasks that require specific
      complementary behavior from the two agents. Results suggest that the proposed
      technique, which relies on a minimum degree of task-level pre-programming, can
      achieve an enhanced physical human-robot interaction performance and deliver
      appropriate level of assistance to the human operator.

PMID- 28436881
TI  - Modulating Lateral Geniculate Nucleus Neuronal Firing for Visual Prostheses: A
      Kalman Filter-Based Strategy.
AB  - Developing visual prostheses that target inner brain structures along the visual
      pathway represent a new hope for patients with completely damaged early visual
      pathway sites. One of the major challenges in the development of subcortical and
      cortical visual prostheses is tuning electrical stimulation that could optimally
      induce desired visual percepts. In this paper, we propose a Kalman filter-based
      strategy that could be used to identify electrical stimulation patterns that
      mimic a specific visual input for thalamic visual prostheses. We demonstrate the
      performance of the proposed strategy using a population of lateral geniculate
      nucleus neurons modeled using an adapted generalized non-linear model. A mean
      correlation of 0.69 is obtained between visually evoked and electrically evoked
      responses-driven using the proposed strategy-for an optimal electrode-placement
      setup. In addition, we demonstrate the performance for a random electrode
      placement setup in which a mean correlation of 0.26 is obtained. For this latter
      setup, our analysis reveals an inversely proportional relationship between the
      obtained correlation and the distance between each neuron and the nearest
      electrode. The proposed strategy could be thus utilized to tune and enhance the
      performance of thalamic visual prostheses as well as other prosthesis systems.

PMID- 28436878
TI  - Biofeedback for Gait Retraining Based on Real-Time Estimation of Tibiofemoral
      Joint Contact Forces.
AB  - Biofeedback assisted rehabilitation and intervention technologies have the
      potential to modify clinically relevant biomechanics. Gait retraining has been
      used to reduce the knee adduction moment, a surrogate of medial tibiofemoral
      joint loading often used in knee osteoarthritis research. In this paper, we
      present an electromyogram-driven neuromusculoskeletal model of the lower-limb to
      estimate, in real-time, the tibiofemoral joint loads. The model included 34
      musculotendon units spanning the hip, knee, and ankle joints. Full-body inverse
      kinematics, inverse dynamics, and musculotendon kinematics were solved in real
      time from motion capture and force plate data to estimate the knee medial
      tibiofemoral contact force (MTFF). We analyzed five healthy subjects while they
      were walking on an instrumented treadmill with visual biofeedback of their MTFF.
      Each subject was asked to modify their gait in order to vary the magnitude of
      their MTFF. All subjects were able to increase their MTFF, whereas only three
      subjects could decrease it, and only after receiving verbal suggestions about
      possible gait modification strategies. Results indicate the important role of
      knee muscle activation patterns in modulating the MTFF. While this paper focused
      on the knee, the technology can be extended to examine the musculoskeletal tissue
      loads at different sites of the human body.

PMID- 28436882
TI  - Home-Based Therapy After Stroke Using the Hand Spring Operated Movement Enhancer
      (HandSOME).
AB  - In previous work, we developed a lightweight wearable hand exoskeleton (Hand
      Spring Operated Movement Enhancer) that improves range of motion and function in
      laboratory testing. In this pilot study, we added the ability to log movement
      data for extended periods and recruited ten chronic stroke subjects to use the
      device during reach and grasp task practice at home for 1.5 h/day, five days per
      week, and for four weeks. Seven subjects completed the study, performing 448 +/-
      651 hand movements per training day. After training, impairment was reduced (Fugl
      Meyer test; gain = 4.9 +/- 4.1; p = .039) and function was improved (Action
      Research Arm Test; gain = 3.3 +/- 2.6; p = .032). There was a significant
      correlation between gains in the Action Research Arm Test and the number of
      movements during training (r = 0.90; p = .005). Proximal arm control also
      improved, as evidenced by a significant reduction in the reach path ratio (p =
      0.038). Five subjects responded well to the treatment, having gains of six points
      or more on the Fugl-Meyer or action research arm test, and achieving significant
      gains in digit extension (gain = 19.8 +/- 10.2 degrees ; p = 0.024). However, all
      of the gains that were significant immediately after training were no longer
      significant at the three month follow-up. This treatment approach appears
      promising, but longer periods of home training may be needed to achieve
      sustainable gains.

PMID- 28436883
TI  - A Bipartite Network and Resource Transfer-Based Approach to Infer lncRNA
      Environmental Factor Associations.
AB  - Phenotypes and diseases are often determined by the complex interactions between
      genetic factors and environmental factors (EFs). However, compared with protein
      coding genes and microRNAs, there is a paucity of computational methods for
      understanding the associations between long non-coding RNAs (lncRNAs) and EFs. In
      this study, we focused on the associations between lncRNA and EFs. By using the
      common miRNA partners of any pair of lncRNA and EF, based on the competing
      endogenous RNA (ceRNA) hypothesis and the technique of resources transfer within
      the experimentally-supported lncRNA-miRNA and miRNA-EF association bipartite
      networks, we propose an algorithm for predicting new lncRNA-EF associations.
      Results show that, compared with another recently-proposed method, our approach
      is capable of predicting more credible lncRNA-EF associations. These results
      support the validity of our approach to predict biologically significant
      associations, which could lead to a better understanding of the molecular
      processes.

PMID- 28436884
TI  - Novelty Indicator for Enhanced Prioritization of Predicted Gene Ontology
      Annotations.
AB  - Biomolecular controlled annotations have become pivotal in computational biology,
      because they allow scientists to analyze large amounts of biological data to
      better understand test results, and to infer new knowledge. Yet, biomolecular
      annotation databases are incomplete by definition, like our knowledge of biology,
      and might contain errors and inconsistent information. In this context, machine
      learning algorithms able to predict and prioritize new annotations are both
      effective and efficient, especially if compared with time-consuming trials of
      biological validation. To limit the possibility that these techniques predict
      obvious and trivial high-level features, and to help prioritize their results, we
      introduce a new element that can improve accuracy and relevance of the results of
      an annotation prediction and prioritization pipeline. We propose a novelty
      indicator able to state the level of "originality" of the annotations predicted
      for a specific gene to Gene Ontology (GO) terms. This indicator, joint with our
      previously introduced prediction steps, helps by prioritizing the most novel
      interesting annotations predicted. We performed an accurate biological functional
      analysis of the prioritized annotations predicted with high accuracy by our
      indicator and previously proposed methods. The relevance of our biological
      findings proves effectiveness and trustworthiness of our indicator and of its
      prioritization of predicted annotations.

PMID- 28436885
TI  - Investigating Correlation between Protein Sequence Similarity and Semantic
      Similarity Using Gene Ontology Annotations.
AB  - Sequence similarity is a commonly used measure to compare proteins. With the
      increasing use of ontologies, semantic (function) similarity is getting
      importance. The correlation between these measures has been applied in the
      evaluation of new semantic similarity methods, and in protein function
      prediction. In this research, we investigate the relationship between the two
      similarity methods. The results suggest absence of a strong correlation between
      sequence and semantic similarities. There is a large number of proteins with low
      sequence similarity and high semantic similarity. We observe that Pearson's
      correlation coefficient is not sufficient to explain the nature of this
      relationship. Interestingly, the term semantic similarity values above 0 and
      below 1 do not seem to play a role in improving the correlation. That is, the
      correlation coefficient depends only on the number of common GO terms in proteins
      under comparison, and the semantic similarity measurement method does not
      influence it. Semantic similarity and sequence similarity have a distinct
      behavior. These findings are of significant effect for future works on protein
      comparison, and will help understand the semantic similarity between proteins in
      a better way.

PMID- 28436886
TI  - DNA Assembly with De Bruijn Graphs Using an FPGA Platform.
AB  - This paper presents an FPGA implementation of a DNA assembly algorithm, called
      Ray, initially developed to run on parallel CPUs. The OpenCL language is used and
      the focus is placed on modifying and optimizing the original algorithm to better
      suit the new parallelization tool and the radically different hardware
      architecture. The results show that the execution time is roughly one fourth that
      of the CPU and factoring energy consumption yields a tenfold savings.

PMID- 28436887
TI  - Optimal Block-Based Trimming for Next Generation Sequencing.
AB  - Read trimming is a fundamental first step of the analysis of next generation
      sequencing (NGS) data. Traditionally, it is performed heuristically, and
      algorithmic work in this area has been neglected. Here, we address this topic and
      formulate three optimization problems for block-based trimming (truncating the
      same low-quality positions at both ends for all reads and removing low-quality
      truncated reads). We find that all problems are NP-hard. Hence, we investigate
      the approximability of the problems. Two of them are NP-hard to approximate.
      However, the non-random distribution of quality scores in NGS data sets makes it
      tempting to speculate that quality constraints for read positions are typically
      satisfied by fulfilling quality constraints for reads. Thus, we propose three
      relaxed problems and develop efficient polynomial-time algorithms for them
      including heuristic speed-up techniques and parallelizations. We apply these
      optimized block trimming algorithms to 12 data sets from three species, four
      sequencers, and read lengths ranging from 36 to 101 bp and find that (i) the
      omitted constraints are indeed almost always satisfied, (ii) the optimized read
      trimming algorithms typically yield a higher number of untrimmed bases than
      traditional heuristics, and (iii) these results can be generalized to alternative
      objective functions beyond counting the number of untrimmed bases.

PMID- 28436888
TI  - Neuromorphic Hardware Architecture Using the Neural Engineering Framework for
      Pattern Recognition.
AB  - We present a hardware architecture that uses the neural engineering framework
      (NEF) to implement large-scale neural networks on field programmable gate arrays
      (FPGAs) for performing massively parallel real-time pattern recognition. NEF is a
      framework that is capable of synthesising large-scale cognitive systems from
      subnetworks and we have previously presented an FPGA implementation of the NEF
      that successfully performs nonlinear mathematical computations. That work was
      developed based on a compact digital neural core, which consists of 64 neurons
      that are instantiated by a single physical neuron using a time-multiplexing
      approach. We have now scaled this approach up to build a pattern recognition
      system by combining identical neural cores together. As a proof of concept, we
      have developed a handwritten digit recognition system using the MNIST database
      and achieved a recognition rate of 96.55%. The system is implemented on a state
      of-the-art FPGA and can process 5.12 million digits per second. The architecture
      and hardware optimisations presented offer high-speed and resource-efficient
      means for performing high-speed, neuromorphic, and massively parallel pattern
      recognition and classification tasks.

PMID- 28436889
TI  - Design and Implementation of a Tactile Stimulation Device to Increase Auditory
      Discrimination.
AB  - Reading is a complex process that requires various simultaneous brain processes.
      One of the most common types of reading disorders is developmental dyslexia, and
      one of the objectives of speech therapy sessions for children with developmental
      dyslexia is to increase their auditory discrimination. One of the most commonly
      used Auditory Discrimination Tests (ADTs) is Wepman's  Auditory Discrimination
      Test (WADT). It includes minimal pair words categorized by characteristics of
      vowels and consonants. The goal of this research is to design and implement a
      tactile stimulation device based on Wepman's test to increase auditory
      discrimination in children with developmental dyslexia in therapy sessions, so
      that while playing each word for the children, vibrational cues are presented to
      their left palm and fingers. The vibrational cues provided by 23 vibration motors
      can notify the child of the difference or similarity between the words. First,
      the device was evaluated by being applied on six female participants aged 6 to 8
      with no hearing disabilities and no developmental dyslexia. Scores obtained from
      the healthy children showed that they can perceive the tactile function of the
      device. Then, function of the device was tested on 8-year-old twin girls with
      developmental dyslexia. The test was conducted as a controlled experiment. One of
      the twins participated in speech therapy treatment, while the other practiced
      with the device. During the study, three sessions were allocated to determine the
      baseline of auditory discrimination, three sessions to the intervention, and two
      sessions (the first, one week and the second, three weeks after the intervention
      sessions) to determine the children's auditory discrimination (follow-up). The
      analysis of trend variations and changes in mean showed that both the speech
      therapy and the intervention based on practicing with the device were effective
      in increasing children's auditory discrimination (Percentage of Non-overlapping
      Data = 100%). The results were stable three weeks after the intervention
      sessions. Therefore, using the device in speech therapy sessions can be useful
      and effective in improving auditory discrimination.

PMID- 28436891
TI  - Off-Policy Reinforcement Learning for Synchronization in Multiagent Graphical
      Games.
AB  - This paper develops an off-policy reinforcement learning (RL) algorithm to solve
      optimal synchronization of multiagent systems. This is accomplished by using the
      framework of graphical games. In contrast to traditional control protocols, which
      require complete knowledge of agent dynamics, the proposed off-policy RL
      algorithm is a model-free approach, in that it solves the optimal synchronization
      problem without knowing any knowledge of the agent dynamics. A prescribed control
      policy, called behavior policy, is applied to each agent to generate and collect
      data for learning. An off-policy Bellman equation is derived for each agent to
      learn the value function for the policy under evaluation, called target policy,
      and find an improved policy, simultaneously. Actor and critic neural networks
      along with least-square approach are employed to approximate target control
      policies and value functions using the data generated by applying prescribed
      behavior policies. Finally, an off-policy RL algorithm is presented that is
      implemented in real time and gives the approximate optimal control policy for
      each agent using only measured data. It is shown that the optimal distributed
      policies found by the proposed algorithm satisfy the global Nash equilibrium and
      synchronize all agents to the leader. Simulation results illustrate the
      effectiveness of the proposed method.

PMID- 28436890
TI  - In-Situ Force Augmentation Improves Surface Contact and Force Control.
AB  - Surgeons routinely perform surgery with noisy, sub-threshold, or obscured visual
      and haptic feedback, either due to the necessary surgical approach, or because
      the systems on which they are operating are exceedingly delicate. Technological
      solutions incorporating haptic feedback augmentation have been proposed to
      address these difficulties, but the consequences for motor control have not been
      directly investigated and quantified. In this paper, we present two isometric
      force generation tasks performed with a hand-held robotic tool that provides in
      situ augmentation of force sensation. An initial study indicated that
      magnification helps the operator maintain a desired supra-threshold target force
      in the absence of visual feedback. We further found that such force magnification
      reduces the mean and standard deviation of applied forces, and reduces the
      magnitude of power in the 4 to 7 Hz band corresponding to tremor. Specific
      benefits to stability, voluntary control, and tremor were observed in the pull
      direction, which has been previously identified as more dexterous compared to
      push.

PMID- 28436892
TI  - GoDec+: Fast and Robust Low-Rank Matrix Decomposition Based on Maximum
      Correntropy.
AB  - GoDec is an efficient low-rank matrix decomposition algorithm. However, optimal
      performance depends on sparse errors and Gaussian noise. This paper aims to
      address the problem that a matrix is composed of a low-rank component and unknown
      corruptions. We introduce a robust local similarity measure called correntropy to
      describe the corruptions and, in doing so, obtain a more robust and faster low
      rank decomposition algorithm: GoDec+. Based on half-quadratic optimization and
      greedy bilateral paradigm, we deliver a solution to the maximum correntropy
      criterion (MCC)-based low-rank decomposition problem. Experimental results show
      that GoDec+ is efficient and robust to different corruptions including Gaussian
      noise, Laplacian noise, salt & pepper noise, and occlusion on both synthetic and
      real vision data. We further apply GoDec+ to more general applications including
      classification and subspace clustering. For classification, we construct an
      ensemble subspace from the low-rank GoDec+ matrix and introduce an MCC-based
      classifier. For subspace clustering, we utilize GoDec+ values low-rank matrix for
      MCC-based self-expression and combine it with spectral clustering. Face
      recognition, motion segmentation, and face clustering experiments show that the
      proposed methods are effective and robust. In particular, we achieve the state-of
      the-art performance on the Hopkins 155 data set and the first 10 subjects of
      extended Yale B for subspace clustering.

PMID- 28436893
TI  - A Parallel Multiclassification Algorithm for Big Data Using an Extreme Learning
      Machine.
AB  - As data sets become larger and more complicated, an extreme learning machine
      (ELM) that runs in a traditional serial environment cannot realize its ability to
      be fast and effective. Although a parallel ELM (PELM) based on MapReduce to
      process large-scale data shows more efficient learning speed than identical ELM
      algorithms in a serial environment, some operations, such as intermediate results
      stored on disks and multiple copies for each task, are indispensable, and these
      operations create a large amount of extra overhead and degrade the learning speed
      and efficiency of the PELMs. In this paper, an efficient ELM based on the Spark
      framework (SELM), which includes three parallel subalgorithms, is proposed for
      big data classification. By partitioning the corresponding data sets reasonably,
      the hidden layer output matrix calculation algorithm, matrix decomposition
      algorithm, and matrix decomposition algorithm perform most of the computations
      locally. At the same time, they retain the intermediate results in distributed
      memory and cache the diagonal matrix as broadcast variables instead of several
      copies for each task to reduce a large amount of the costs, and these actions
      strengthen the learning ability of the SELM. Finally, we implement our SELM
      algorithm to classify large data sets. Extensive experiments have been conducted
      to validate the effectiveness of the proposed algorithms. As shown, our SELM
      achieves an speedup on a cluster with ten nodes, and reaches a speedup with 15
      nodes, an speedup with 20 nodes, a speedup with 25 nodes, a speedup with 30
      nodes, and a speedup with 35 nodes.

PMID- 28436894
TI  - Online Learning Algorithms Can Converge Comparably Fast as Batch Learning.
AB  - Online learning algorithms in a reproducing kernel Hilbert space associated with
      convex loss functions are studied. We show that in terms of the expected excess
      generalization error, they can converge comparably fast as corresponding kernel
      based batch learning algorithms. Under mild conditions on loss functions and
      approximation errors, fast learning rates and finite sample upper bounds are
      established using polynomially decreasing step-size sequences. For some commonly
      used loss functions for classification, such as the logistic and the -norm hinge
      loss functions with , the learning rates are the same as those for Tikhonov
      regularization and can be of order , which are nearly optimal up to a logarithmic
      factor. Our novelty lies in a sharp estimate for the expected values of norms of
      the learning sequence (or an inductive argument to uniformly bound the expected
      risks of the learning sequence in expectation) and a refined error decomposition
      for online learning algorithms.

PMID- 28436895
TI  - Online Learning Algorithm Based on Adaptive Control Theory.
AB  - This paper proposes a new online learning algorithm which is based on adaptive
      control (AC) theory, thus, we call this proposed algorithm as AC algorithm.
      Comparing to the gradient descent (GD) and exponential gradient (EG) algorithm
      which have been applied to online prediction problems, we find a new form of AC
      theory for online prediction problems and investigate two key questions: how to
      get a new update law which has a tighter upper bound on the error than the square
      loss? How to compare the upper bound for accumulated losses for the three
      algorithms? We obtain a new update law which fully utilizes model reference AC
      theory. Moreover, we present upper bound on the worst-case expected loss for AC
      algorithm and compare it with previously known bounds for the GD and EG
      algorithm. The loss bound we get in this paper is a time-varying function, which
      provides increasingly accurate estimates for upper bound. The AC algorithm has a
      much smaller loss only if the number of the samples meets certain conditions
      which can be seen in this paper. We also performed experiments which show that
      our update law is reasonably feasible and our upper bound is quite tight on both
      simple artificial and real data sets. The main contributions of this paper are
      twofold. First of all, we develop a new online algorithm called AC algorithm, and
      second, we obtain improved bounds, see Theorems 2-4 in this paper.

PMID- 28436896
TI  - Online Hashing.
AB  - Although hash function learning algorithms have achieved great success in recent
      years, most existing hash models are off-line, which are not suitable for
      processing sequential or online data. To address this problem, this paper
      proposes an online hash model to accommodate data coming in stream for online
      learning. Specifically, a new loss function is proposed to measure the similarity
      loss between a pair of data samples in hamming space. Then, a structured hash
      model is derived and optimized in a passive-aggressive way. Theoretical analysis
      on the upper bound of the cumulative loss for the proposed online hash model is
      provided. Furthermore, we extend our online hashing (OH) from a single model to a
      multimodel OH that trains multiple models so as to retain diverse OH models in
      order to avoid biased update. The competitive efficiency and effectiveness of the
      proposed online hash models are verified through extensive experiments on several
      large-scale data sets as compared with related hashing methods.

PMID- 28436897
TI  - Tensor-Factorized Neural Networks.
AB  - The growing interests in multiway data analysis and deep learning have drawn
      tensor factorization (TF) and neural network (NN) as the crucial topics.
      Conventionally, the NN model is estimated from a set of one-way observations.
      Such a vectorized NN is not generalized for learning the representation from
      multiway observations. The classification performance using vectorized NN is
      constrained, because the temporal or spatial information in neighboring ways is
      disregarded. More parameters are required to learn the complicated data
      structure. This paper presents a new tensor-factorized NN (TFNN), which tightly
      integrates TF and NN for multiway feature extraction and classification under a
      unified discriminative objective. This TFNN is seen as a generalized NN, where
      the affine transformation in an NN is replaced by the multilinear and multiway
      factorization for tensor-based NN. The multiway information is preserved through
      layerwise factorization. Tucker decomposition and nonlinear activation are
      performed in each hidden layer. The tensor-factorized error backpropagation is
      developed to train TFNN with the limited parameter size and computation time.
      This TFNN can be further extended to realize the convolutional TFNN (CTFNN) by
      looking at small subtensors through the factorized convolution. Experiments on
      real-world classification tasks demonstrate that TFNN and CTFNN attain
      substantial improvement when compared with an NN and a convolutional NN,
      respectively.

PMID- 28436898
TI  - Extended Polynomial Growth Transforms for Design and Training of Generalized
      Support Vector Machines.
AB  - Growth transformations constitute a class of fixed-point multiplicative update
      algorithms that were originally proposed for optimizing polynomial and rational
      functions over a domain of probability measures. In this paper, we extend this
      framework to the domain of bounded real variables which can be applied towards
      optimizing the dual cost function of a generic support vector machine (SVM). The
      approach can, therefore, not only be used to train traditional soft-margin binary
      SVMs, one-class SVMs, and probabilistic SVMs but can also be used to design novel
      variants of SVMs with different types of convex and quasi-convex loss functions.
      In this paper, we propose an efficient training algorithm based on polynomial
      growth transforms, and compare and contrast the properties of different SVM
      variants using several synthetic and benchmark data sets. The preliminary
      experiments show that the proposed multiplicative update algorithm is more
      scalable and yields better convergence compared to standard quadratic and
      nonlinear programming solvers. While the formulation and the underlying
      algorithms have been validated in this paper only for SVM-based learning, the
      proposed approach is general and can be applied to a wide variety of optimization
      problems and statistical learning models.

PMID- 28436899
TI  - Adaptive Backstepping-Based Neural Tracking Control for MIMO Nonlinear Switched
      Systems Subject to Input Delays.
AB  - This brief proposes a new neural-network (NN)-based adaptive output tracking
      control scheme for a class of disturbed multiple-input multiple-output uncertain
      nonlinear switched systems with input delays. By combining the universal
      approximation ability of radial basis function NNs and adaptive backstepping
      recursive design with an improved multiple Lyapunov function (MLF) scheme, a
      novel adaptive neural output tracking controller design method is presented for
      the switched system. The feature of the developed design is that different
      coordinate transformations are adopted to overcome the conservativeness caused by
      adopting a common coordinate transformation for all subsystems. It is shown that
      all the variables of the resulting closed-loop system are semiglobally uniformly
      ultimately bounded under a class of switching signals in the presence of MLF and
      that the system output can follow the desired reference signal. To demonstrate
      the practicability of the obtained result, an adaptive neural output tracking
      controller is designed for a mass-spring-damper system.

PMID- 28436900
TI  - A Discrete-Time Recurrent Neural Network for Solving Rank-Deficient Matrix
      Equations With an Application to Output Regulation of Linear Systems.
AB  - This paper presents a discrete-time recurrent neural network approach to solving
      systems of linear equations with two features. First, the system of linear
      equations may not have a unique solution. Second, the system matrix is not known
      precisely, but a sequence of matrices that converges to the unknown system matrix
      exponentially is known. The problem is motivated from solving the output
      regulation problem for linear systems. Thus, an application of our main result
      leads to an online solution to the output regulation problem for linear systems.

PMID- 28436901
TI  - On Better Exploring and Exploiting Task Relationships in Multitask Learning:
      Joint Model and Feature Learning.
AB  - Multitask learning (MTL) aims to learn multiple tasks simultaneously through the
      interdependence between different tasks. The way to measure the relatedness
      between tasks is always a popular issue. There are mainly two ways to measure
      relatedness between tasks: common parameters sharing and common features sharing
      across different tasks. However, these two types of relatedness are mainly
      learned independently, leading to a loss of information. In this paper, we
      propose a new strategy to measure the relatedness that jointly learns shared
      parameters and shared feature representations. The objective of our proposed
      method is to transform the features of different tasks into a common feature
      space in which the tasks are closely related and the shared parameters can be
      better optimized. We give a detailed introduction to our proposed MTL method.
      Additionally, an alternating algorithm is introduced to optimize the nonconvex
      objection. A theoretical bound is given to demonstrate that the relatedness
      between tasks can be better measured by our proposed MTL algorithm. We conduct
      various experiments to verify the superiority of the proposed joint model and
      feature MTL method.

PMID- 28436902
TI  - Learning to Predict Consequences as a Method of Knowledge Transfer in
      Reinforcement Learning.
AB  - The reinforcement learning (RL) paradigm allows agents to solve tasks through
      trial-and-error learning. To be capable of efficient, long-term learning, RL
      agents should be able to apply knowledge gained in the past to new tasks they may
      encounter in the future. The ability to predict actions' consequences may
      facilitate such knowledge transfer. We consider here domains where an RL agent
      has access to two kinds of information: agent-centric information with constant
      semantics across tasks, and environment-centric information, which is necessary
      to solve the task, but with semantics that differ between tasks. For example, in
      robot navigation, environment-centric information may include the robot's
      geographic location, while agent-centric information may include sensor readings
      of various nearby obstacles. We propose that these situations provide an
      opportunity for a very natural style of knowledge transfer, in which the agent
      learns to predict actions' environmental consequences using agent-centric
      information. These predictions contain important information about the
      affordances and dangers present in a novel environment, and can effectively
      transfer knowledge from agent-centric to environment-centric learning systems.
      Using several example problems including spatial navigation and network routing,
      we show that our knowledge transfer approach can allow faster and lower cost
      learning than existing alternatives.

PMID- 28436903
TI  - Robust Multiview Data Analysis Through Collective Low-Rank Subspace.
AB  - Multiview data are of great abundance in real-world applications, since various
      viewpoints and multiple sensors desire to represent the data in a better way.
      Conventional multiview learning methods aimed to learn multiple view-specific
      transformations meanwhile assumed the view knowledge of training, and test data
      were available in advance. However, they would fail when we do not have any prior
      knowledge for the probe data's view information, since the correct view-specific
      projections cannot be utilized to extract effective feature representations. In
      this paper, we develop a collective low-rank subspace (CLRS) algorithm to deal
      with this problem in multiview data analysis. CLRS attempts to reduce the
      semantic gap across multiple views through seeking a view-free low-rank
      projection shared by multiple view-specific transformations. Moreover, we exploit
      low-rank reconstruction to build a bridge between the view-specific features and
      those view-free ones transformed with the CLRS. Furthermore, a supervised cross
      view regularizer is developed to couple the within-class data across different
      views to make the learned collective subspace more discriminative. Our CLRS makes
      our algorithm more flexible when addressing the challenging issue without any
      prior knowledge of the probe data's view information. To that end, two different
      settings of experiments on several multiview benchmarks are designed to evaluate
      the proposed approach. Experimental results have verified the effective
      performance of our proposed method by comparing with the state-of-the-art
      algorithms.

PMID- 28436904
TI  - User Preference-Based Dual-Memory Neural Model With Memory Consolidation
      Approach.
AB  - Memory modeling has been a popular topic of research for improving the
      performance of autonomous agents in cognition related problems. Apart from
      learning distinct experiences correctly, significant or recurring experiences are
      expected to be learned better and be retrieved easier. In order to achieve this
      objective, this paper proposes a user preference-based dual-memory adaptive
      resonance theory network model, which makes use of a user preference to encode
      memories with various strengths and to learn and forget at various rates. Over a
      period of time, memories undergo a consolidation-like process at a rate
      proportional to the user preference at the time of encoding and the frequency of
      recall of a particular memory. Consolidated memories are easier to recall and are
      more stable. This dual-memory neural model generates distinct episodic memories
      and a flexible semantic-like memory component. This leads to an enhanced
      retrieval mechanism of experiences through two routes. The simulation results are
      presented to evaluate the proposed memory model based on various kinds of cues
      over a number of trials. The experimental results on Mybot are also presented.
      The results verify that not only are distinct experiences learned correctly but
      also that experiences associated with higher user preference and recall frequency
      are consolidated earlier. Thus, these experiences are recalled more easily
      relative to the unconsolidated experiences.

PMID- 28436905
TI  - Robust Structured Nonnegative Matrix Factorization for Image Representation.
AB  - Dimensionality reduction has attracted increasing attention, because high
      dimensional data have arisen naturally in numerous domains in recent years. As
      one popular dimensionality reduction method, nonnegative matrix factorization
      (NMF), whose goal is to learn parts-based representations, has been widely
      studied and applied to various applications. In contrast to the previous
      approaches, this paper proposes a novel semisupervised NMF learning framework,
      called robust structured NMF, that learns a robust discriminative representation
      by leveraging the block-diagonal structure and the -norm (especially when ) loss
      function. Specifically, the problems of noise and outliers are well addressed by
      the -norm ( ) loss function, while the discriminative representations of both the
      labeled and unlabeled data are simultaneously learned by explicitly exploring the
      block-diagonal structure. The proposed problem is formulated as an optimization
      problem with a well-defined objective function solved by the proposed iterative
      algorithm. The convergence of the proposed optimization algorithm is analyzed
      both theoretically and empirically. In addition, we also discuss the
      relationships between the proposed method and some previous methods. Extensive
      experiments on both the synthetic and real-world data sets are conducted, and the
      experimental results demonstrate the effectiveness of the proposed method in
      comparison to the state-of-the-art methods.

PMID- 28436906
TI  - Nonlinear Decoupling Control With ANFIS-Based Unmodeled Dynamics Compensation for
      a Class of Complex Industrial Processes.
AB  - Complex industrial processes are multivariable and generally exhibit strong
      coupling among their control loops with heavy nonlinear nature. These make it
      very difficult to obtain an accurate model. As a result, the conventional and
      data-driven control methods are difficult to apply. Using a twin-tank level
      control system as an example, a novel multivariable decoupling control algorithm
      with adaptive neural-fuzzy inference system (ANFIS)-based unmodeled dynamics (UD)
      compensation is proposed in this paper for a class of complex industrial
      processes. At first, a nonlinear multivariable decoupling controller with UD
      compensation is introduced. Different from the existing methods, the
      decomposition estimation algorithm using ANFIS is employed to estimate the UD,
      and the desired estimating and decoupling control effects are achieved. Second,
      the proposed method does not require the complicated switching mechanism which
      has been commonly used in the literature. This significantly simplifies the
      obtained decoupling algorithm and its realization. Third, based on some new
      lemmas and theorems, the conditions on the stability and convergence of the
      closed-loop system are analyzed to show the uniform boundedness of all the
      variables. This is then followed by the summary on experimental tests on a
      heavily coupled nonlinear twin-tank system that demonstrates the effectiveness
      and the practicability of the proposed method.

PMID- 28436907
TI  - Reliability of Lagged Poincare Plot Parameters in Ultrashort Heart Rate
      Variability Series: Application on Affective Sounds.
AB  - The number of studies about ultrashort cardiovascular time series is increasing
      because of the demand for mobile applications in telemedicine and e-health
      monitoring. However, the current literature still needs a proper validation of
      heartbeat nonlinear dynamics assessment from ultrashort time series. This paper
      reports on the reliability of the Lagged Poincare Plot (LPP) parameters
      calculated from ultrashort cardiovascular time series. Reliability is studied on
      simulated as well as on real RR series. Simulated RR series are generated and LPP
      parameters estimated for ultrashort time series (from 15 to 60 s) are compared to
      those estimated from 1 h. All LPP parameters estimated from time series longer
      than 35 s presented a Spearman's correlation coefficient higher than 0.99. RR
      series acquired from 32 healthy subjects during 5-min resting state sessions are
      used to test the LPP approach in experimental data. The usefulness of ultrashort
      term parameters in real data is accomplished also studying their ability to
      discriminate positive and negative valence of auditory stimuli taken from the
      International Affective Digitized Sound System (IADS) dataset. The achieved
      accuracies in the recognition of elicitation along the valence dimension, using
      only the LPP parameters, were of 77.78% for 1 min 28 s series, and of 79.17% for
      35 s series.

PMID- 28436908
TI  - A Knowledge-Constrained Access Control Model for Protecting Patient Privacy in
      Hospital Information Systems.
AB  - Current access control mechanisms of the hospital information system can hardly
      identify the real access intention of system users. A relaxed access control
      increases the risk of compromise of patient privacy. To reduce unnecessary access
      of patient information by hospital staff, this paper proposes a knowledge
      constrained role-based access control (KC-RBAC) model in which a variety of
      medical domain knowledge is considered in access control. Based on the proposed
      Purpose Tree and knowledge-involved algorithms, the model can dynamically define
      the boundary of access to the patient information according to the context, which
      helps to protect patient privacy by controlling access. Compared with the role
      based access control model, KC-RBAC can effectively protect patient information
      according to the results of the experiments.

PMID- 28436909
TI  - Pulse Transit Time Measurement Using Seismocardiogram, Photoplethysmogram, and
      Acoustic Recordings: Evaluation and Comparison.
AB  - This work proposes a novel method of pulse transit time (PTT) measurement. The
      proximal arterial location data are collected from seismocardiogram (SCG)
      recordings by placing a micro-electromechanical accelerometer on the chest wall.
      The distal arterial location data are recorded using an acoustic sensor placed
      inside the ear. The performance of distal location recordings is evaluated by
      comparing SCG-acoustic and SCG-photoplethysmogram (PPG) measurements. PPG and
      acoustic performances under motion noise are also compared. Experimental results
      suggest comparable performances for the acoustic-based and PPG-based devices. The
      feasibility of each PTT measurement method is validated for blood pressure
      evaluations and its limitations are analyzed.

PMID- 28436910
TI  - Discovering the Relationship Between Generalization and Uncertainty by
      Incorporating Complexity of Classification.
AB  - The generalization ability of a classifier learned from a training set is usually
      dependent on the classifier's uncertainty, which is often described by the
      fuzziness of the classifier's outputs on the training set. Since the exact
      dependency relation between generalization and uncertainty of a classifier is
      quite complicated, it is difficult to clearly or explicitly express this relation
      in general. This paper shows a specific study on this relation from the viewpoint
      of complexity of classification by choosing extreme learning machines as the
      classification algorithms. It concludes that the generalization ability of a
      classifier is statistically becoming better with the increase of uncertainty when
      the complexity of the classification problem is relatively high, and the
      generalization ability is statistically becoming worse with the increase of
      uncertainty when the complexity is relatively low. This paper tries to provide
      some useful guidelines for improving the generalization ability of classifiers by
      adjusting uncertainty based on the problem complexity.

PMID- 28436911
TI  - Sampled-Data Fuzzy Control for Nonlinear Coupled Parabolic PDE-ODE Systems.
AB  - In this paper, a sampled-data fuzzy control problem is addressed for a class of
      nonlinear coupled systems, which are described by a parabolic partial
      differential equation (PDE) and an ordinary differential equation (ODE).
      Initially, the nonlinear coupled system is accurately represented by the Takagi
      Sugeno (T-S) fuzzy coupled parabolic PDE-ODE model. Then, based on the T-S fuzzy
      model, a novel time-dependent Lyapunov functional is used to design a sampled
      data fuzzy controller such that the closed-loop coupled system is exponentially
      stable, where the sampled-data fuzzy controller consists of the ODE state
      feedback and the PDE static output feedback under spatially averaged
      measurements. The stabilization condition is presented in terms of a set of
      linear matrix inequalities. Finally, simulation results on the control of a
      hypersonic rocket car are given to illustrate the effectiveness of the proposed
      design method.

PMID- 28436912
TI  - Distributed Position-Based Consensus of Second-Order Multiagent Systems With
      Continuous/Intermittent Communication.
AB  - This paper considers the position-based consensus in a network of agents with
      double-integrator dynamics and directed topology. Two types of distributed
      observer algorithms are proposed to solve the consensus problem by utilizing
      continuous and intermittent position measurements, respectively, where each
      observer does not interact with any other observers. For the case of continuous
      communication between network agents, some convergence conditions are derived for
      reaching consensus in the network with a single constant delay or multiple time
      varying delays on the basis of the eigenvalue analysis and the descriptor method.
      When the network agents can only obtain intermittent position data from local
      neighbors at discrete time instants, the consensus in the network without time
      delay or with nonuniform delays is investigated by using the Wirtinger's
      inequality and the delayed-input approach. Numerical examples are given to
      illustrate the theoretical analysis.

PMID- 28436913
TI  - Synchronization of Reaction-Diffusion Neural Networks With Dirichlet Boundary
      Conditions and Infinite Delays.
AB  - This paper is concerned with synchronization for a class of reaction-diffusion
      neural networks with Dirichlet boundary conditions and infinite discrete time
      varying delays. By utilizing theories of partial differential equations, Green's
      formula, inequality techniques, and the concept of comparison, algebraic criteria
      are presented to guarantee master-slave synchronization of the underlying
      reaction-diffusion neural networks via a designed controller. Additionally,
      sufficient conditions on exponential synchronization of reaction-diffusion neural
      networks with finite time-varying delays are established. The proposed criteria
      herein enhance and generalize some published ones. Three numerical examples are
      presented to substantiate the validity and merits of the obtained theoretical
      results.

PMID- 28436914
TI  - A Time Variant Log-Linear Learning Approach to the SET K-COVER Problem in
      Wireless Sensor Networks.
AB  - Toward the global optimality of the SET K-COVER problem in wireless sensor
      networks, we view each sensor node as a rational player and propose a time
      variant log-linear learning algorithm (TVLLA) that relies on local information
      only. By defining the local utility as the normalized area covered by one node
      alone, we formulate the problem as a spatial potential game. The resulting
      optimal Nash equilibria correspond to the optimal partition. Such equilibria are
      obtained by designing a time varying parameter that approaches infinity with
      time. Using inhomogeneous Markov chain theory, we prove that the TVLLA guarantees
      convergence to the optimal solution with probability 1. Comparison results
      against traditional methods demonstrate that the algorithm can also provide
      better near-optimal solutions in a reasonable computation time than the state-of
      the-art. Our findings pave a new way to reach the global optimality of the SET K
      COVER problem in a distributed manner as well as other potential games from the
      view of self-organized optimization.

PMID- 28436915
TI  - An Adaptive Multiobjective Particle Swarm Optimization Based on Multiple Adaptive
      Methods.
AB  - Multiobjective particle swarm optimization (MOPSO) algorithms have attracted much
      attention for their promising performance in solving multiobjective optimization
      problems (MOPs). In this paper, an adaptive MOPSO (AMOPSO) algorithm, based on a
      hybrid framework of the solution distribution entropy and population spacing (SP)
      information, is developed to improve the search performance in terms of
      convergent speed and precision. First, an adaptive global best (gBest) selection
      mechanism, based on the solution distribution entropy, is introduced to analyze
      the evolutionary tendency and balance the diversity and convergence of
      nondominated solutions in the archive. Second, an adaptive flight parameter
      adjustment mechanism, using the population SP information, is proposed to obtain
      the distribution of particles with suitable diversity and convergence, which can
      balance the global exploration and local exploitation abilities of the particles.
      Third, based on the gBest selection mechanism and the adaptive flight parameter
      mechanism, this proposed AMOPSO algorithm not only has high accuracy, but also
      attain a set of optimal solutions with better diversity. Finally, the performance
      of the proposed AMOPSO algorithm is validated and compared with other five state
      of-the-art algorithms on a number of benchmark problems and water distribution
      system. The experimental results validate the effectiveness of the proposed
      AMOPSO algorithm, as well as demonstrate that AMOPSO outperforms other MOPSO
      algorithms in solving MOPs.

PMID- 28436916
TI  - A New Differential Evolution Algorithm for Minimax Optimization in Robust Design.
AB  - Minimax optimization, which is actively involved in numerous robust design
      problems, aims at pursuing the solutions with best worst-case performances.
      Although considerable research has been devoted to the development of minimax
      optimization algorithms, there still exist several fundamental limitations for
      existing approaches, e.g., restriction on problem types, excessively high
      computational cost, and low optimization efficiency. To address these issues, a
      minimax differential evolution algorithm is proposed in this paper. First, a
      novel bottom-boosting scheme enables the algorithm to identify the promising
      solutions in a reliable yet efficient manner. After that, a partial-regeneration
      strategy together with a new mutation operator contribute to an in-depth
      exploration over solution space. Finally, a proper integration of these newly
      proposed mechanisms leads to an algorithmic structure that can appropriately
      handle various types of problems. Empirical comparison with seven famous methods
      demonstrates the statistical superiority of the proposed algorithm. Successful
      applications in two open problems of robust design further validate the
      effectiveness of the new approach.

PMID- 28436917
TI  - Fault Estimation Observer Design for Discrete-Time Takagi-Sugeno Fuzzy Systems
      Based on Homogenous Polynomially Parameter-Dependent Lyapunov Functions.
AB  - This paper investigates the problem of robust fault estimation (FE) observer
      design for discrete-time Takagi-Sugeno fuzzy systems via homogenous polynomially
      parameter-dependent Lyapunov functions. First, a novel framework of the fuzzy FE
      observer is established with the help of a maximum-minimum-priority-based
      switching mechanism. Then, for every activated switching case, a targeted result
      is achieved by the aid of exploring an important property of improved homogenous
      polynomials. Since the helpful information of the underlying system can be duly
      updated and effectively utilized at every sampled point, the conservatism of
      previous results is availably reduced. Furthermore, the proposed result is
      further improved by eliminating those redundant terms of the introduced matrix
      valued variables. Simulation results based on a discrete-time nonlinear truck
      trailer model are provided to show the advantages of the theoretic result that is
      developed in this paper.

PMID- 28436918
TI  - An integrated and highly sensitive ultrafast acoustoelectric imaging system for
      biomedical applications.
AB  - Direct imaging of the electrical activation of the heart is crucial to better
      understand and diagnose diseases linked to arrhythmias. This work presents an
      ultrafast acoustoelectric imaging (UAI) system for direct and non-invasive
      ultrafast mapping of propagating current densities using the acoustoelectric
      effect. Acoustoelectric imaging is based on the acoustoelectric effect, the
      modulation of the medium's electrical impedance by a propagating ultrasonic wave.
      UAI triggers this effect with plane wave emissions to image current densities. An
      ultrasound research platform was fitted with electrodes connected to high common
      mode rejection ratio amplifiers and sampled by up to 128 independent channels.
      The sequences developed allow for both real-time display of acoustoelectric maps
      and long ultrafast acquisition with fast off-line processing. The system was
      evaluated by injecting controlled currents into a saline pool via copper wire
      electrodes. Sensitivity to low current and low acoustic pressure were measured
      independently. Contrast and spatial resolution were measured for varying numbers
      of plane waves and compared to line per line acoustoelectric imaging with focused
      beams at equivalent peak pressure. Temporal resolution was assessed by measuring
      time-varying current densities associated with sinusoidal currents. Complex
      intensity distributions were also imaged in 3D. Electrical current densities were
      detected for injected currents as low as 0.56 mA. UAI outperformed conventional
      focused acoustoelectric imaging in terms of contrast and spatial resolution when
      using 3 and 13 plane waves or more, respectively. Neighboring sinusoidal currents
      with opposed phases were accurately imaged and separated. Time-varying currents
      were mapped and their frequency accurately measured for imaging frame rates up to
      500 Hz. Finally, a 3D image of a complex intensity distribution was obtained. The
      results demonstrated the high sensitivity of the UAI system proposed. The plane
      wave based approach provides a highly flexible trade-off between frame rate,
      resolution and contrast. In conclusion, the UAI system shows promise for non
      invasive, direct and accurate real-time imaging of electrical activation in vivo.

PMID- 28436919
TI  - A machine learning method for fast and accurate characterization of depth-of
      interaction gamma cameras.
AB  - Measuring the depth-of-interaction (DOI) of gamma photons enables increasing the
      resolution of emission imaging systems. Several design variants of DOI-sensitive
      detectors have been recently introduced to improve the performance of scanners
      for positron emission tomography (PET). However, the accurate characterization of
      the response of DOI detectors, necessary to accurately measure the DOI, remains
      an unsolved problem. Numerical simulations are, at the state of the art,
      imprecise, while measuring directly the characteristics of DOI detectors
      experimentally is hindered by the impossibility to impose the depth-of
      interaction in an experimental set-up. In this article we introduce a machine
      learning approach for extracting accurate forward models of gamma imaging devices
      from simple pencil-beam measurements, using a nonlinear dimensionality reduction
      technique in combination with a finite mixture model. The method is purely data
      driven, not requiring simulations, and is applicable to a wide range of detector
      types. The proposed method was evaluated both in a simulation study and with data
      acquired using a monolithic gamma camera designed for PET (the cMiCE detector),
      demonstrating the accurate recovery of the DOI characteristics. The combination
      of the proposed calibration technique with maximum- a posteriori estimation of
      the coordinates of interaction provided a depth resolution of  ~1.14 mm for the
      simulated PET detector and  ~1.74 mm for the cMiCE detector. The software and
      experimental data are made available at
      http://occiput.mgh.harvard.edu/depthembedding/.

PMID- 28436920
TI  - Hybrid 3D printing and electrodeposition approach for controllable 3D alginate
      hydrogel formation.
AB  - Calcium alginate hydrogels are widely used as biocompatible materials in a
      substantial number of biomedical applications. This paper reports on a hybrid 3D
      printing and electrodeposition approach for forming 3D calcium alginate hydrogels
      in a controllable manner. Firstly, a specific 3D hydrogel printing system is
      developed by integrating a customized ejection syringe with a conventional 3D
      printer. Then, a mixed solution of sodium alginate and CaCO3 nanoparticles is
      filled into the syringe and can be continuously ejected out of the syringe nozzle
      onto a conductive substrate. When applying a DC voltage (~5 V) between the
      substrate (anode) and the nozzle (cathode), the Ca2+ released from the CaCO3
      particles can crosslink the alginate to form calcium alginate hydrogel on the
      substrate. To elucidate the gel formation mechanism and better control the gel
      growth, we can further establish and verify a gel growth model by considering
      several key parameters, i.e., applied voltage and deposition time. The
      experimental results indicate that the alginate hydrogel of various 3D structures
      can be formed by controlling the movement of the 3D printer. A cell viability
      test is conducted and shows that the encapsulated cells in the gel can maintain a
      high survival rate (~99% right after gel formation). This research establishes a
      reliable method for the controllable formation of 3D calcium alginate hydrogel,
      exhibiting great potential for use in basic biology and applied biomedical
      engineering.

PMID- 28436921
TI  - Feasibility study of entrance and exit dose measurements at the contra lateral
      breast with alanine/electron spin resonance dosimetry in volumetric modulated
      radiotherapy of breast cancer.
AB  - The Physikalisch-Technische Bundesanstalt has established a secondary standard
      measurement system for the dose to water, D W, based on alanine/ESR (Anton et al
      2013 Phys. Med. Biol. 58 3259-82). The aim of this study was to test the
      established measurement system for the out-of-field measurements of inpatients
      with breast cancer. A set of five alanine pellets were affixed to the skin of
      each patient at the contra lateral breast beginning at the sternum and extending
      over the mammilla to the distal surface. During 28 fractions with 2.2 Gy per
      fraction, the accumulated dose was measured in four patients. A cone beam
      computer tomography (CBCT) scan was generated for setup purposes before every
      treatment. The reference CT dataset was registered rigidly and deformably to the
      CBCT dataset for 28 fractions. To take the actual alanine pellet position into
      account, the dose distribution was calculated for every fraction using the Acuros
      XB algorithm. The results of the ESR measurements were compared to the calculated
      doses. The maximum dose measured at the sternum was 19.9 Gy  +/-  0.4 Gy,
      decreasing to 6.8 Gy  +/-  0.2 Gy at the mammilla and 4.5 Gy  +/-  0.1 Gy at the
      distal surface of the contra lateral breast. The absolute differences between the
      calculated and measured doses ranged from  -1.9 Gy to 0.9 Gy. No systematic error
      could be seen. It was possible to achieve a combined standard uncertainty of
      1.63% for D W  =  5 Gy for the measured dose. The alanine/ESR method is feasible
      for in vivo measurements.

PMID- 28436922
TI  - The feasibility of manual parameter tuning for deformable breast MR image
      registration from a multi-objective optimization perspective.
AB  - Deformable image registration is typically formulated as an optimization problem
      involving a linearly weighted combination of terms that correspond to objectives
      of interest (e.g. similarity, deformation magnitude). The weights, along with
      multiple other parameters, need to be manually tuned for each application, a task
      currently addressed mainly via trial-and-error approaches. Such approaches can
      only be successful if there is a sensible interplay between parameters,
      objectives, and desired registration outcome. This, however, is not well
      established. To study this interplay, we use multi-objective optimization, where
      multiple solutions exist that represent the optimal trade-offs between the
      objectives, forming a so-called Pareto front. Here, we focus on weight tuning. To
      study the space a user has to navigate during manual weight tuning, we randomly
      sample multiple linear combinations. To understand how these combinations relate
      to desirability of registration outcome, we associate with each outcome a mean
      target registration error (TRE) based on expert-defined anatomical landmarks.
      Further, we employ a multi-objective evolutionary algorithm that optimizes the
      weight combinations, yielding a Pareto front of solutions, which can be directly
      navigated by the user. To study how the complexity of manual weight tuning
      changes depending on the registration problem, we consider an easy problem, prone
      to-prone breast MR image registration, and a hard problem, prone-to-supine breast
      MR image registration. Lastly, we investigate how guidance information as an
      additional objective influences the prone-to-supine registration outcome. Results
      show that the interplay between weights, objectives, and registration outcome
      makes manual weight tuning feasible for the prone-to-prone problem, but very
      challenging for the harder prone-to-supine problem. Here, patient-specific, multi
      objective weight optimization is needed, obtaining a mean TRE of 13.6 mm without
      guidance information reduced to 7.3 mm with guidance information, but also
      providing a Pareto front that exhibits an intuitively sensible interplay between
      weights, objectives, and registration outcome, allowing outcome selection.

PMID- 28436923
TI  - Fourteen Important Concepts Regarding Moral Distress.
AB  - I suggest that we may want to strive, over time, to change our present
      professional-cultural view, from one that sees an expression of moral distress as
      a threat, to a professional-cultural view that welcomes these challenges. Such an
      effort to better medicine would not only include dissenting clinicians, but
      patients (and their loved ones) as well.

PMID- 28436924
TI  - Harnessing the Promise of Moral Distress: A Call for Re-Orientation.
AB  - Despite over three decades of research into the sources and costs of what has
      become an "epidemic" of moral distress among healthcare professionals, spanning
      many clinical disciplines and roles, there has been little significant progress
      in effectively addressing moral distress. We believe the persistent sense of
      frustration, helplessness, and despair still dominating the clinical moral
      distress narrative signals a need for re-orientation in the way moral distress is
      understood and worked with. Most fundamentally, moral distress reveals moral
      investment and energy. It is the troubled call of conscience, an expression of
      fidelity to moral commitments seen as imperiled or compromised. It is crucial
      that we find ways to empower clinicians in heeding this call-to support
      clinicians' moral agency and voice, foster their moral resilience, and facilitate
      their ability to contribute to needed reform within the organizations and systems
      in which they work. These objectives must inform creative expansion in the design
      of strategies for addressing moral distress in the day-to-day of clinical
      practice. We include suggestions about promising directions such strategies might
      take in the hope of spurring further innovation within clinical environments.

PMID- 28436925
TI  - Focus More on Causes and Less on Symptoms of Moral Distress.
AB  - In this commentary on Carse and Rushton's call for reorientation of moral
      distress, we state agreement with the authors that the discourse of moral
      distress should refocus on the moral components of integrity. We then explain how
      our philosophical taxonomy of moral distress, mentioned by the authors, appeals
      to moral integrity. In this process, we clarify our taxonomy's appeal to
      Aristotle's concept of akrasia. We conclude by offering support of Carse and
      Rushton's challenge to organizations to strengthen moral integrity by fostering
      resilience.

PMID- 28436926
TI  - Using Moral Distress for Organizational Improvement.
AB  - Moral distress is a major problem for nurses, other clinicians, and the health
      system itself. But if properly understood and responded to, it is also a
      promising guide for healthcare improvement. When individuals experience moral
      distress or burnout, their reports must be seen as crucial data requiring careful
      attention to the individuals and to the organization. Distress and burnout will
      often point to important opportunities for system improvements, which may in turn
      reduce the experience of distress. For this potential virtuous cycle to happen,
      individuals must be able to articulate their concerns without fear of
      retribution, and organizational leaders must be able to listen in an undefensive,
      improvement-oriented manner.

PMID- 28436927
TI  - Looking at the Positive Side of Moral Distress: Why It's a Problem.
AB  - Moral distress, is, at its core, an organizational problem. It is experienced on
      a personal level, but its causes originate within the system itself. In this
      commentary, we argue that moral distress is not inherently good, that effective
      interventions must address the external sources of moral distress, and that while
      there is a place for resilience in the healthcare professions, it cannot be an
      effective antidote to moral distress.

PMID- 28436928
TI  - Moral Distress: Conscious and Unconscious Feelings.
AB  - In analyzing moral distress, perhaps greater attention should be given to the
      possible implicit sources of feelings of distress, as well as explicit sources.

PMID- 28436929
TI  - When Not to Rescue: An Ethical Analysis of Best Practices for Cardiopulmonary
      Resuscitation and Emergency Cardiac Care.
AB  - It is now a default obligation to provide cardiopulmonary resuscitation (CPR), in
      the absence of knowledge of a patient's or surrogate's wishes to the contrary. We
      submit that it is time to re-evaluate this position. Attempting CPR should be
      subject to the same scrutiny demanded of other medical interventions that involve
      balancing a great benefit against grievous harms.

PMID- 28436930
TI  - A Framework for Ethical Decision Making in the Rehabilitation of Patients with
      Anosognosia.
AB  - Currently, the number of patients diagnosed with impaired self-awareness of their
      own deficits after brain injury-anosognosia-is increasing. One reason is a
      growing understanding of this multifaceted phenomenon. Another is the development
      and accessibility of alternative measurements that allow more detailed diagnoses.
      Anosognosia can adversely affect successful rehabilitation, as often patients
      lack confidence in the need for treatment. Planning such treatment can become a
      complex process full of ethical dilemmas. To date, there is no systematic way to
      deal with different aspects of anosognosia rehabilitation planning. This is the
      first article to present a framework for ethical decision making in establishing
      rehabilitation plans that are focused on increasing patients' self-awareness of
      their own deficits after brain injury. It concentrates especially on addressing
      the ethical dilemmas that may arise, and describes stepwise procedures that can
      be applied to distinct theoretical approaches, as well as diagnostic and
      rehabilitation methods. To show the flexibility of the use of this framework,
      alternative approaches are discussed.

PMID- 28436931
TI  - Family Loyalty as a Cultural Obstacle to Good Care: The Case of Mrs. Indira.
AB  - What is the responsibility of the physician when a capacitated patient assigns
      decision-making authority to a surrogate who does not act in the patient's best
      interest?

PMID- 28436932
TI  - Complexities in Caregiving: Comforts, Cultures, Countries, Conversations, and
      Contracts.
AB  - As depicted in the case of Mrs. Indira, decision making by patients and
      surrogates may be complicated by multiple factors, including care, comfort,
      country, and culture.

PMID- 28436933
TI  - Legal Briefing: New Penalties for Ignoring Advance Directives and Do-Not
      Resuscitate Orders.

PMID- 28436934
TI  - Biopolymers codelivering engineered T cells and STING agonists can eliminate
      heterogeneous tumors.
AB  - Therapies using T cells that are programmed to express chimeric antigen receptors
      (CAR T cells) consistently produce positive results in patients with hematologic
      malignancies. However, CAR T cell treatments are less effective in solid tumors
      for several reasons. First, lymphocytes do not efficiently target CAR T cells;
      second, solid tumors create an immunosuppressive microenvironment that
      inactivates T cell responses; and third, solid cancers are typified by phenotypic
      diversity and thus include cells that do not express proteins targeted by the
      engineered receptors, enabling the formation of escape variants that elude CAR T
      cell targeting. Here, we have tested implantable biopolymer devices that deliver
      CAR T cells directly to the surfaces of solid tumors, thereby exposing them to
      high concentrations of immune cells for a substantial time period. In
      immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we
      found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors
      more effectively than does systemic delivery of the same cells. We have also
      demonstrated that codelivery of stimulator of IFN genes (STING) agonists
      stimulates immune responses to eliminate tumor cells that are not recognized by
      the adoptively transferred lymphocytes. Thus, these devices may improve the
      effectiveness of CAR T cell therapy in solid tumors and help protect against the
      emergence of escape variants.

PMID- 28436935
TI  - TNF superfamily receptor OX40 triggers invariant NKT cell pyroptosis and liver
      injury.
AB  - Tissue-resident immune cells play a key role in local and systemic immune
      responses. The liver, in particular, hosts a large number of invariant natural
      killer T (iNKT) cells, which are involved in diverse immune responses. However,
      the mechanisms that regulate survival and homeostasis of liver iNKT cells are
      poorly defined. Here we have found that liver iNKT cells constitutively express
      the costimulatory TNF superfamily receptor OX40 and that OX40 stimulation results
      in massive pyroptotic death of iNKT cells, characterized by the release of potent
      proinflammatory cytokines that induce liver injury. This OX40/NKT pyroptosis
      pathway also plays a key role in concanavalin A-induced murine hepatitis.
      Mechanistically, we demonstrated that liver iNKT cells express high levels of
      caspase 1 and that OX40 stimulation activates caspase 1 via TNF receptor
      associated factor 6-mediated recruitment of the paracaspase MALT1. We also found
      that activation of caspase 1 in iNKT cells results in processing of pro-IL-1beta
      to mature IL-1beta as well as cleavage of the pyroptotic protein gasdermin D,
      which generates a membrane pore-forming fragment to produce pyroptotic cell
      death. Thus, our study has identified OX40 as a death receptor for iNKT cells and
      uncovered a molecular mechanism of pyroptotic cell death. These findings may have
      important clinical implications in the development of OX40-directed therapies.

PMID- 28436936
TI  - The U2AF1S34F mutation induces lineage-specific splicing alterations in
      myelodysplastic syndromes.
AB  - Mutations of the splicing factor-encoding gene U2AF1 are frequent in the
      myelodysplastic syndromes (MDS), a myeloid malignancy, and other cancers.
      Patients with MDS suffer from peripheral blood cytopenias, including anemia, and
      an increasing percentage of bone marrow myeloblasts. We studied the impact of the
      common U2AF1S34F mutation on cellular function and mRNA splicing in the main cell
      lineages affected in MDS. We demonstrated that U2AF1S34F expression in human
      hematopoietic progenitors impairs erythroid differentiation and skews
      granulomonocytic differentiation toward granulocytes. RNA sequencing of erythroid
      and granulomonocytic colonies revealed that U2AF1S34F induced a higher number of
      cassette exon splicing events in granulomonocytic cells than in erythroid cells.
      U2AF1S34F altered mRNA splicing of many transcripts that were expressed in both
      cell types in a lineage-specific manner. In hematopoietic progenitors, the
      introduction of isoform changes identified in the U2AF1S34F target genes H2AFY,
      encoding an H2A histone variant, and STRAP, encoding serine/threonine kinase
      receptor-associated protein, recapitulated phenotypes associated with U2AF1S34F
      expression in erythroid and granulomonocytic cells, suggesting a causal link.
      Furthermore, we showed that isoform modulation of H2AFY and STRAP rescues the
      erythroid differentiation defect in U2AF1S34F MDS cells, suggesting that splicing
      modulators could be used therapeutically. These data have critical implications
      for understanding MDS phenotypic heterogeneity and support the development of
      therapies targeting splicing abnormalities.

PMID- 28436937
TI  - Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with
      hypophosphatasia.
AB  - BACKGROUND: Hypophosphatasia (HPP) is a rare genetic disorder resulting in
      variable alterations of bone formation and mineralization that are caused by
      mutations in the ALPL gene, encoding the tissue-nonspecific alkaline phosphatase
      (ALP) enzyme. METHODS: In this phase IIA open-label, single-center, intra
      patient, dose-escalating study, adult patients with HPP received 3 ascending
      intravenous doses of 5, 10, and 20 mg/kg BPS804, a fully human anti-sclerostin
      monoclonal antibody, on days 1, 15, and 29, respectively. Patients were followed
      for 16 weeks after the last dose. We assessed the pharmacodynamics,
      pharmacokinetics, preliminary efficacy, and safety of BPS804 administrations at
      specified intervals during treatment and follow-up. RESULTS: Eight patients (mean
      age 47.8 years) were enrolled in the study (6 females, 2 males). BPS804 treatment
      increased mean ALP and bone-specific ALP enzymatic activity between days 2 and
      29. Transient increases in the bone formation markers procollagen type-I N
      terminal propeptide (PINP), osteocalcin, and parathyroid hormone as well as a
      transient decrease in the bone resorption marker C-telopeptide of type I collagen
      (CTX-1) were observed. Lumbar spine bone mineral density showed a mean increase
      by day 85 and at end of study. Treatment-associated adverse events were mild and
      transient. CONCLUSION: BPS804 treatment was well tolerated and resulted in
      increases in bone formation biomarkers and bone mineral density, suggesting that
      sclerostin inhibition could be applied to enhance bone mineral density,
      stability, and regeneration in non-life-threatening clinical situations in adults
      with HPP. TRIAL REGISTRATION: Clinicaltrials.gov NCT01406977. FUNDING: Novartis
      Institutes for BioMedical Research, Basel, Switzerland.

PMID- 28436938
TI  - Geminin facilitates FoxO3 deacetylation to promote breast cancer cell metastasis.
AB  - Geminin expression is essential for embryonic development and the maintenance of
      chromosomal integrity. In spite of this protective role, geminin is also
      frequently overexpressed in human cancers and the molecular mechanisms underlying
      its role in tumor progression remain unclear. The histone deacetylase HDAC3
      modulates transcription factors to activate or suppress transcription. Little is
      known about how HDAC3 specifies substrates for modulation among highly homologous
      transcription factor family members. Here, we have demonstrated that geminin
      selectively couples the transcription factor forkhead box O3 (FoxO3) to HDAC3,
      thereby specifically facilitating FoxO3 deacetylation. We determined that geminin
      associated HDAC3 deacetylates FoxO3 to block its transcriptional activity,
      leading to downregulation of the downstream FoxO3 target Dicer, an RNase that
      suppresses metastasis. Breast cancer cells depleted of geminin or HDAC3 exhibited
      poor metastatic potential that was attributed to reduced suppression of the FoxO3
      Dicer axis. Moreover, elevated levels of geminin, HDAC3, or both together with
      decreased FoxO3 acetylation and reduced Dicer expression were detected in
      aggressive human breast cancer specimens. These results underscore a prominent
      role for geminin in promoting breast cancer metastasis via the enzyme-substrate
      coupling mechanism in HDAC3-FoxO3 complex formation.

PMID- 28436939
TI  - An inflammatory bowel disease-risk variant in INAVA decreases pattern recognition
      receptor-induced outcomes.
AB  - Inflammatory bowel disease (IBD) is characterized by dysregulation in both
      cytokines and responses to intestinal microbes, and proper regulation of pattern
      recognition receptor (PRR) signaling is critical for intestinal immune
      homeostasis. Altered functions for the IBD risk locus containing rs7554511, which
      encompasses the C1orf106 gene (recently named INAVA), and roles for the protein
      encoded by the INAVA gene are unknown. Here, we investigated the role of INAVA
      and INAVA genotype in regulating PRR-initiated outcomes in primary human cells.
      Both peripheral and intestinal myeloid cells expressed INAVA. Upon PRR
      stimulation, INAVA was required for optimal MAPK and NF-kappaB activation,
      cytokine secretion, and intracellular bacterial clearance. INAVA recruited 14-3
      3tau, thereby contributing to recruitment of a signaling complex that amplified
      downstream signals and cytokines. Further, INAVA enhanced bacterial clearance by
      regulating reactive oxygen, reactive nitrogen, and autophagy pathways.
      Macrophages from rs7554511 C risk carriers expressed lower levels of INAVA RNA
      and protein. Lower expression was attributed in part to decreased transcription
      mediated directly by the intronic region containing the rs7554511 C variant. In
      rs7554511 C risk carrier macrophages, lower INAVA expression led to decreased PRR
      induced activation of MAPK and NF-kappaB pathways, cytokines, and bacterial
      clearance pathways. Thus, IBD-associated polymorphisms in INAVA modulate PRR
      initiated signaling, cytokines, and intracellular bacterial clearance, likely
      contributing to intestinal immune homeostasis.

PMID- 28436940
TI  - Disruption of spatiotemporal hypoxic signaling causes congenital heart disease in
      mice.
AB  - Congenital heart disease (CHD) represents the most prevalent inborn anomaly. Only
      a minority of CHD cases are attributed to genetic causes, suggesting a major role
      of environmental factors. Nonphysiological hypoxia during early pregnancy induces
      CHD, but the underlying reasons are unknown. Here, we have demonstrated that
      cells in the mouse heart tube are hypoxic, while cardiac progenitor cells (CPCs)
      expressing islet 1 (ISL1) in the secondary heart field (SHF) are normoxic. In
      ISL1+ CPCs, induction of hypoxic responses caused CHD by repressing Isl1 and
      activating NK2 homeobox 5 (Nkx2.5), resulting in decreased cell proliferation and
      enhanced cardiomyocyte specification. We found that HIF1alpha formed a complex
      with the Notch effector hes family bHLH transcription factor 1 (HES1) and the
      protein deacetylase sirtuin 1 (SIRT1) at the Isl1 gene. This complex repressed
      Isl1 in the hypoxic heart tube or following induction of ectopic hypoxic
      responses. Subsequently, reduced Isl1 expression abrogated ISL1-dependent
      recruitment of histone deacetylases HDAC1/5, inhibiting Nkx2.5 expression.
      Inactivation of Sirt1 in ISL1+ CPCs blocked Isl1 suppression via the
      HIF1alpha/HES1/SIRT1 complex and prevented CHDs induced by pathological hypoxia.
      Our results indicate that spatial differences in oxygenation of the developing
      heart serve as signals to control CPC expansion and cardiac morphogenesis. We
      propose that physiological hypoxia coordinates homeostasis of CPCs, providing
      mechanistic explanations for some nongenetic causes of CHD.

PMID- 28436942
TI  - Diversity and ecological adaptations in Palaeogene lichens.
AB  - Lichens are highly specialized symbioses between heterotrophic fungi and
      photoautotrophic green algae or cyanobacteria. The mycobionts of many lichens
      produce morphologically complex thalli to house their photobionts. Lichens play
      important roles in ecosystems and have been used as indicators of environmental
      change. Here we report the finding of 152 new fossil lichens from European
      Palaeogene amber, and hence increase the total number of known fossil lichens
      from 15 to 167. Most of the fossils represent extant lineages of the
      Lecanoromycetes, an almost exclusively lichen-symbiotic class of Ascomycota. The
      fossil lichens show a wide diversity of morphological adaptations that attached
      epiphytic thalli to their substrates, helped to combine external water storage
      with effective gas exchange and facilitated the simultaneous reproduction and
      dispersal of both partners in symbiosis. The fossil thallus morphologies suggest
      that the climate of European Palaeogene amber forests was relatively humid and
      most likely temperate.

PMID- 28436941
TI  - INSR gene polymorphisms correlate with sensitivity to platinum-based chemotherapy
      and prognosis in patients with epithelial ovarian cancer.
AB  - This study aimed to investigate the correlation between INSR gene polymorphisms
      on platinum-based chemotherapy sensitivity and prognosis in epithelial ovarian
      cancer (EOC). A total of 339 EOC patients receiving postoperative chemotherapy
      were recruited for the study. Tag single-nucleotide polymorphism of INSR gene was
      screened from HapMap combined with available literature. Frequency distribution
      of genotypes and alleles in INSR gene was sequenced by ABI3100-Avant. Compared
      with CC+GC genotype, INSR rs2252673 GG genotype and rs3745546 CC genotype showed
      less platinum-based chemotherapy sensitivity in EOC patients (odds ratio
      (OR)=0.269, 95% confidence interval (CI)=0.159~0.456; OR=0.445, 95%
      CI=0.214~0.926, respectively), as well as serous EOC patients (OR=0.083, 95%
      CI=0.024~0.278; OR=0.235, 95%CI=0.053~1.041, respectively). The clinical
      characteristics including age, clinical stage, histological grade and residual
      lesion size were significantly related with chemosensitivity to platinum drugs
      and mortality in EOC patients. According to Kaplan-Meier curve, compared with
      CC+GC genotype, rs2252673 GG genotype showed significantly decreased survival
      rate in EOC patients (P<0.05). Cox regression model indicated that rs2252673, age
      and clinical stage were independent risk factors for the prognosis in EOC (all
      P<0.05). These findings indicate that INSR rs2252673 and rs3745546 polymorphisms
      were associated with sensitivity to platinum-based chemotherapy in EOC patients
      and rs2252673 polymorphism may be an independent risk factor for EOC prognosis.

PMID- 28436943
TI  - Transient cell-specific EXO70A1 activity in the CASP domain and Casparian strip
      localization.
AB  - In a striking case of evolutionary convergence, polarized cell layers with ring
      like diffusion barriers have evolved in both plant and animal lineages
      independently. In plants, ring-like Casparian strips become localized by the
      CASPARIAN STRIP MEMBRANE DOMAIN PROTEINS (CASPs). The mechanism of this striking
      localization, however, has remained enigmatic. Here we present a genetic screen
      aimed at isolating determinants of CASP localization. One of the mutants, lord of
      the rings 2 (lotr2)/exo70a1, displays dramatic de-localization of CASPs into
      randomly localized microdomains. EXO70A1 is a subunit of the exocyst complex, a
      central component of secretion in eukaryotes. Irradiation of EXO70 subunit genes
      in plants has suggested specialization of this conserved complex. Intriguingly,
      lotr2/exo70a1 does neither affect secretion of the CASPs, nor that of other
      membrane proteins in the endodermis, thus separating exocyst activity in
      localization from a general defect in secretion. Our results establish EXO70A1 as
      a central player in Casparian strip formation, generating a transient positional
      information that will be translated into a precisely localized cell wall
      modification.

PMID- 28436945
TI  - ADAR1 controls apoptosis of stressed cells by inhibiting Staufen1-mediated mRNA
      decay.
AB  - Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double
      stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that
      activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological
      function of the ADAR1p110 isoform, which is usually located in the nucleus, is
      largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110
      by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export
      from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses
      apoptosis in stressed cells by protecting many antiapoptotic gene transcripts
      that contain 3'-untranslated-region dsRNA structures primarily comprising
      inverted Alu repeats. ADAR1p110 competitively inhibits binding of Staufen1 to the
      3'-untranslated-region dsRNAs and antagonizes Staufen1-mediated mRNA decay. Our
      study reveals a new stress-response mechanism in which human ADAR1p110 and
      Staufen1 regulate surveillance of a set of mRNAs required for survival of
      stressed cells.

PMID- 28436944
TI  - Active and poised promoter states drive folding of the extended HoxB locus in
      mouse embryonic stem cells.
AB  - Gene expression states influence the 3D conformation of the genome through poorly
      understood mechanisms. Here, we investigate the conformation of the murine HoxB
      locus, a gene-dense genomic region containing closely spaced genes with distinct
      activation states in mouse embryonic stem (ES) cells. To predict possible folding
      scenarios, we performed computer simulations of polymer models informed with
      different chromatin occupancy features that define promoter activation states or
      binding sites for the transcription factor CTCF. Single-cell imaging of the locus
      folding was performed to test model predictions. While CTCF occupancy alone fails
      to predict the in vivo folding at genomic length scale of 10 kb, we found that
      homotypic interactions between active and Polycomb-repressed promoters co
      occurring in the same DNA fiber fully explain the HoxB folding patterns imaged in
      single cells. We identify state-dependent promoter interactions as major drivers
      of chromatin folding in gene-dense regions.

PMID- 28436946
TI  - Essential role for Bim in mediating the apoptotic and antitumor activities of
      immunotoxins.
AB  - Protein synthesis is crucial for regulating cell homeostasis and, when
      unrestricted, it can lead to tumorigenesis. Immunotoxins derived from Pseudomonas
      exotoxin are antibody-toxin fusion proteins that inhibit protein synthesis of
      mammalian cells via ADP-ribosylation of the eukaryotic elongation factor-2. Here
      we investigate the role of the Bcl-2 family proteins in the response of cancer
      cells to immunotoxin challenge. Besides the well-known reduction of the
      prosurvival Bcl-2 family member, Mcl-1, following inhibition of protein
      synthesis, we show for the first time that immunotoxins also reduce the levels of
      selected proapoptotic BH-3-only proteins. Among these, only Bim protein levels
      correlated with the ability of immunotoxins to induce an apoptotic response. To
      support our findings, we verified that a Bim knockout completely abolished
      immunotoxin-mediated apoptosis. Further, mice bearing either wild-type or Bid
      knockout tumors responded to immunotoxin treatment with a decrease in growth
      kinetics, whereas mice engrafted with Bim knockout tumors showed no reduction in
      tumor size or prolongation of survival following immunotoxin treatment. From
      these results, we conclude that Bim expression is a major susceptibility factor
      for tumor cell death and, as such, constitutes a potential biomarker that could
      be evaluated before immunotoxin treatment. In support of this hypothesis,
      clinically, we analyzed patient cells before immunotoxin treatment and report
      that samples of hairy cell leukemia with high levels of Bim protein responded
      with a greater decrease in leukemic cell count compared with those samples
      expressing a low level of Bim.

PMID- 28436947
TI  - Dedifferentiation into blastomere-like cancer stem cells via formation of
      polyploid giant cancer cells.
AB  - Our recent perplexing findings that polyploid giant cancer cells (PGCCs) acquired
      embryonic-like stemness and were capable of tumor initiation raised two important
      unanswered questions: how do PGCCs acquire such stemness, and to which stage of
      normal development do PGCCs correspond. Intriguingly, formation of giant cells
      due to failed mitosis/cytokinesis is common in the blastomere stage of the
      preimplantation embryo. However, the relationship between PGCCs and giant
      blastomeres has never been studied. Here, we tracked the fate of single PGCCs
      following paclitaxel-induced mitotic failure. Morphologically, early spheroids
      derived from PGCCs were indistinguishable from human embryos at the blastomere,
      polyploid blastomere, compaction, morula and blastocyst-like stages by light,
      scanning electron or three-dimensional confocal scanning microscopy. Formation of
      PGCCs was associated with activation of senescence, while budding of daughter
      cells was associated with senescence escape. PGCCs showed time- and space
      dependent activation of expression of the embryonic stem cell markers OCT4,
      NANOG, SOX2 and SSEA1 and lacked expression of Xist. PGCCs acquired mesenchymal
      phenotype and were capable of differentiation into all three germ layers in
      vitro. The embryonic-like stemness of PGCCs was associated with nuclear
      accumulation of YAP, a key mediator of the Hippo pathway. Spheroids derived from
      single PGCCs grew into a wide spectrum of human neoplasms, including germ cell
      tumors, high-grade and low-grade carcinomas and benign tissues. Daughter cells
      derived from PGCCs showed attenuated capacity for invasion and increased
      resistance to paclitaxel. We also observed formation of PGCCs and
      dedifferentiation in ovarian cancer specimens from patients treated with
      chemotherapy. Taken together, our findings demonstrate that PGCCs represent
      somatic equivalents of blastomeres, the most primitive cancer stem cells reported
      to date. Thus, our studies reveal an evolutionarily conserved archaic embryonic
      program in somatic cells that can be de-repressed for oncogenesis. Our work
      offers a new paradigm for cancer origin and disease relapse.

PMID- 28436949
TI  - p14ARF interacts with the focal adhesion kinase and protects cells from anoikis.
AB  - The ARF protein functions as an important sensor of hyper-proliferative stimuli
      restricting cell proliferation through both p53-dependent and -independent
      pathways. Although to date the majority of studies on ARF have focused on its
      anti-proliferative role, few studies have addressed whether ARF may also have pro
      survival functions. Here we show for the first time that during the process of
      adhesion and spreading ARF re-localizes to sites of active actin polymerization
      and to focal adhesion points where it interacts with the phosphorylated focal
      adhesion kinase. In line with its recruitment to focal adhesions, we observe that
      hampering ARF function in cancer cells leads to gross defects in cytoskeleton
      organization resulting in apoptosis through a mechanism dependent on the Death
      Associated Protein Kinase. Our data uncover a novel function for p14ARF in
      protecting cells from anoikis that may reflect its role in anchorage
      independence, a hallmark of malignant tumor cells.

PMID- 28436948
TI  - Mitochondrial elongation-mediated glucose metabolism reprogramming is essential
      for tumour cell survival during energy stress.
AB  - To date, mechanisms of tumour cell survival under energy stress are not well
      understood. Cumulative evidence is beginning to reveal that specific
      mitochondrial morphologies are often associated with energetic states and
      survival of cells. However, the functional roles of mitochondria in the metabolic
      adaptation of tumour cells to energy stress remain to be elucidated. In this
      study, we first investigated the changes in mitochondrial morphology induced by
      nutrition deprivation in tumour cells, and the underlying molecular mechanism. We
      then systematically explored glucose metabolism reprogramming by energy stress
      induced alteration of mitochondrial morphology and its effect on tumour cell
      survival. Our results showed that starvation treatment resulted in a dramatic
      mitochondrial elongation, which was mainly mediated by DRP1S637 phosphorylation
      through protein kinase A activation and subsequent suppression of mitochondrial
      translocation of DRP1. We further observed that tumour cells under an energy
      stress condition exhibited a clear shift from glycolysis towards oxidative
      phosphorylation, which was reversed by the recovery of mitochondrial fission
      induced by forced expression of mutant DRP1S637A. Mechanistically, energy stress
      induced mitochondrial elongation facilitated cristae formation and assembly of
      respiratory complexes to enhance oxidative phosphorylation, which in turn
      exhibited a feedback inhibitory effect on glycolysis through NAD+-dependent SIRT1
      activation. In addition, our data indicated that DRP1S637-mediated mitochondrial
      elongation under energy stress was essential for tumour cell survival both in
      vitro and in vivo and predicted poor prognosis of hepatocellular carcinoma
      patients. Overall, our study demonstrates that remodelling of mitochondrial
      morphology plays a critical role in tumour cell adaptation to energy stress by
      reprogramming glucose metabolism.

PMID- 28436950
TI  - MRE11 stability is regulated by CK2-dependent interaction with R2TP complex.
AB  - The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand
      breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11
      cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like
      disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a
      subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for
      the assembly of large protein complexes, such as RNA polymerase II, small
      nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1. The
      MRE11-PIH1D1 interaction is dependent on casein kinase 2 (CK2) phosphorylation of
      two acidic sequences within the MRE11 C terminus containing serines 558/561 and
      688/689. Conversely, the PIH1D1 phospho-binding domain PIH-N is required for
      association with MRE11 phosphorylated by CK2. Consistent with these findings,
      depletion of PIH1D1 resulted in MRE11 destabilization and affected DNA-damage
      repair processes dependent on MRE11. Additionally, mutations of serines 688/689,
      which abolish PIH1D1 binding, also resulted in decreased MRE11 stability. As
      depletion of R2TP frequently leads to instability of its substrates and as
      truncation mutation of MRE11 lacking serines 688/689 leads to decreased levels of
      the MRN complex both in ATLD patients and an ATLD mouse model, our results
      suggest that the MRN complex is a novel R2TP complex substrate and that their
      interaction is regulated by CK2 phosphorylation.

PMID- 28436951
TI  - Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular
      permeability by targeting prolyl hydroxylase and tight junction protein ZO-1.
AB  - Hypoxia plays a critical role during the evolution of malignant cells and tumour
      microenvironment (TME).Tumour-derived exosomes contain informative microRNAs
      involved in the interaction of cancer and stromal cells, thus contributing to
      tissue remodelling of tumour microenvironment. This study aims to clarify how
      hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells.
      Lung cancer cells produce more exosomes under hypoxic conditions than do parental
      cells under normoxic conditions. miR-23a was significantly upregulated in
      exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly
      suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the
      accumulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in endothelial
      cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes
      derived from hypoxic cancer under both normoxic and hypoxic conditions. In
      addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby
      increasing vascular permeability and cancer transendothelial migration.
      Inhibition of miR-23a by inhibitor administration decreased angiogenesis and
      tumour growth in a mouse model. Furthermore, elevated levels of circulating miR
      23a are found in the sera of lung cancer patients, and miR-23a levels are
      positively correlated with proangiogenic activities. Taken together, our study
      reveals the clinical relevance and prognostic value of cancer-derived exosomal
      miR-23a under hypoxic conditions, and investigates a unique intercellular
      communication, mediated by cancer-derived exosomes, which modulates tumour
      vasculature.

PMID- 28436953
TI  - Disruption of direct 3D telomere-TRF2 interaction through two molecularly
      disparate mechanisms is a hallmark of primary Hodgkin and Reed-Sternberg cells.
AB  - In classical Hodgkin's lymphoma (cHL), specific changes in the 3D telomere
      organization cause progression from mononuclear Hodgkin cells (H) to
      multinucleated Reed-Sternberg cells (RS). In a post-germinal center B-cell in
      vitro model, permanent latent membrane protein 1 (LMP1) expression, as observed
      in Epstein-Barr virus (EBV)-associated cHL, results in multinuclearity and
      complex chromosomal aberrations through downregulation of key element of the
      shelterin complex, the telomere repeat binding factor 2 (TRF2). Thus, we
      hypothesized that the three-dimensional (3D) telomere-TRF2 interaction was
      progressively disturbed during transition from H to RS cells. To this end, we
      developed and applied for the first time a combined quantitative 3D TRF2-telomere
      immune fluorescent in situ hybridization (3D TRF2/Telo-Q-FISH) technique to
      monolayers of primary H and RS cells, and adjacent benign internal control
      lymphocytes of lymph node biopsy suspensions from diagnostic lymph node biopsies
      of 14 patients with cHL. We show that H and RS cells are characterized by two
      distinct patterns of disruption of 3D telomere-TRF2 interaction. Disruption
      pattern A is defined by massive attrition of telomere signals and a considerable
      increase of TRF2 signals not associated with telomeres. This pattern is
      restricted to EBV-negative cHL. Disruption pattern B is defined by telomere de
      protection due to an impressive loss of TRF2 signals, physically linked to
      telomeres. This pattern is typical of, but is not restricted to, LMP1+EBV
      associated cHL. In the disruption pattern B group, so-called 'ghost' end-stage RS
      cells, void of both TRF2 and telomere signals, were identified, whether or not
      associated with EBV. Our findings demonstrate that two molecularly disparate
      mechanisms converge on the level of 3D telomere-TRF2 interaction in the formation
      of RS cells.

PMID- 28436952
TI  - Playing polo during mitosis: PLK1 takes the lead.
AB  - Polo-like kinase 1 (PLK1), the prototypical member of the polo-like family of
      serine/threonine kinases, is a pivotal regulator of mitosis and cytokinesis in
      eukaryotes. Many layers of regulation have evolved to target PLK1 to different
      subcellular structures and to its various mitotic substrates in line with its
      numerous functions during mitosis. Collective work is starting to illuminate an
      important set of substrates for PLK1: the mitotic kinases that together ensure
      the fidelity of the cell division process. Amongst these, recent developments
      argue that PLK1 regulates the activity of the histone kinases Aurora B and Haspin
      to define centromere identity, of MPS1 to initiate spindle checkpoint signaling,
      and of BUB1 and its pseudokinase paralog BUBR1 to coordinate spindle checkpoint
      activation and inactivation. Here, we review the recent work describing the
      regulation of these kinases by PLK1. We highlight common themes throughout and
      argue that a major mitotic function of PLK1 is as a master regulator of these key
      kinases.

PMID- 28436954
TI  - Optimized expression-based microdissection of formalin-fixed lung cancer tissue.
AB  - Analysis of specific DNA alterations in precision medicine of tumors is crucially
      important for molecular targeted treatments. Lung cancer is a prototypic example
      and one of the leading causes of cancer-related deaths worldwide. One major
      technical problem of detecting DNA alterations in tissue samples is cellular
      heterogeneity, that is, mixture of tumor and normal cells. Microdissection is an
      important tool to enrich tumor cells from heterogeneous tissue samples. However,
      conventional laser capture microdissection has several disadvantages like user
      dependent selection of regions of interest (ROI), high costs for dissection
      systems and long processing times. ROI selection in expression-based
      microdissection (xMD) directly relies on cancer cell-specific immunostaining.
      Whole-slide irradiation leads to localized energy absorption at the sites of most
      intensive staining and melting of a membrane covering the slide, so that tumor
      cells can be isolated by removing the complete membrane. In this study, we
      optimized xMD of lung cancer tissue by enhancing staining intensity of tumor cell
      specific immunostaining and processing of the stained samples. This optimized
      procedure did not alter DNA quality and resulted in enrichment of mutated EGFR
      DNA from lung adenocarcinoma specimens after xMD. We here also introduce a
      quality control protocol based on digital whole-slide scanning and image analysis
      before and after xMD to quantify selectivity and efficiency of the procedure. In
      summary, this study provides a workflow for xMD, adapted and tested for lung
      cancer tissue that can be used for lung tumor cell dissection before diagnostic
      or investigatory analyses.

PMID- 28436955
TI  - Vitamin A mediates conversion of monocyte-derived macrophages into tissue
      resident macrophages during alternative activation.
AB  - It remains unclear whether activated inflammatory macrophages can adopt features
      of tissue-resident macrophages, or what mechanisms might mediate such a
      phenotypic conversion. Here we show that vitamin A is required for the phenotypic
      conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80intCD206+PD
      L2+MHCII+ macrophages into macrophages with a tissue-resident F4/80hiCD206-PD-L2
      MHCII-UCP1+ phenotype in the peritoneal cavity of mice and during the formation
      of liver granulomas in mice infected with Schistosoma mansoni. The phenotypic
      conversion of F4/80intCD206+ macrophages into F4/80hiCD206- macrophages was
      associated with almost complete remodeling of the chromatin landscape, as well as
      alteration of the transcriptional profiles. Vitamin A-deficient mice infected
      with S. mansoni had disrupted liver granuloma architecture and increased
      mortality, which indicates that failure to convert macrophages from the
      F4/80intCD206+ phenotype to F4/80hiCD206- may lead to dysregulated inflammation
      during helminth infection.

PMID- 28436956
TI  - Identification of subepithelial mesenchymal cells that induce IgA and diversify
      gut microbiota.
AB  - Immunoglobulin A (IgA) maintains a symbiotic equilibrium with intestinal
      microbes. IgA induction in the gut-associated lymphoid tissues (GALTs) is
      dependent on microbial sampling and cellular interaction in the subepithelial
      dome (SED). However it is unclear how IgA induction is predominantly initiated in
      the SED. Here we show that previously unrecognized mesenchymal cells in the SED
      of GALTs regulate bacteria-specific IgA production and diversify the gut
      microbiota. Mesenchymal cells expressing the cytokine RANKL directly interact
      with the gut epithelium to control CCL20 expression and microfold (M) cell
      differentiation. The deletion of mesenchymal RANKL impairs M cell-dependent
      antigen sampling and B cell-dendritic cell interaction in the SED, which results
      in a reduction in IgA production and a decrease in microbial diversity. Thus, the
      subepithelial mesenchymal cells that serve as M cell inducers have a fundamental
      role in the maintenance of intestinal immune homeostasis.

PMID- 28436957
TI  - Pyruvate kinase M2 activation may protect against the progression of diabetic
      glomerular pathology and mitochondrial dysfunction.
AB  - Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and
      therapeutic options for preventing its progression are limited. To identify novel
      therapeutic strategies, we studied protective factors for DN using proteomics on
      glomeruli from individuals with extreme duration of diabetes (l50 years) without
      DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol,
      methylglyoxal and mitochondrial pathways were elevated in individuals without DN.
      In particular, pyruvate kinase M2 (PKM2) expression and activity were
      upregulated. Mechanistically, we showed that hyperglycemia and diabetes decreased
      PKM2 tetramer formation and activity by sulfenylation in mouse glomeruli and
      cultured podocytes. Pkm-knockdown immortalized mouse podocytes had higher levels
      of toxic glucose metabolites, mitochondrial dysfunction and apoptosis. Podocyte
      specific Pkm2-knockout (KO) mice with diabetes developed worse albuminuria and
      glomerular pathology. Conversely, we found that pharmacological activation of
      PKM2 by a small-molecule PKM2 activator, TEPP-46, reversed hyperglycemia-induced
      elevation in toxic glucose metabolites and mitochondrial dysfunction, partially
      by increasing glycolytic flux and PGC-1alpha mRNA in cultured podocytes. In
      intervention studies using DBA2/J and Nos3 (eNos) KO mouse models of diabetes,
      TEPP-46 treatment reversed metabolic abnormalities, mitochondrial dysfunction and
      kidney pathology. Thus, PKM2 activation may protect against DN by increasing
      glucose metabolic flux, inhibiting the production of toxic glucose metabolites
      and inducing mitochondrial biogenesis to restore mitochondrial function.

PMID- 28436958
TI  - Local clearance of senescent cells attenuates the development of post-traumatic
      osteoarthritis and creates a pro-regenerative environment.
AB  - Senescent cells (SnCs) accumulate in many vertebrate tissues with age and
      contribute to age-related pathologies, presumably through their secretion of
      factors contributing to the senescence-associated secretory phenotype (SASP).
      Removal of SnCs delays several pathologies and increases healthy lifespan. Aging
      and trauma are risk factors for the development of osteoarthritis (OA), a chronic
      disease characterized by degeneration of articular cartilage leading to pain and
      physical disability. Senescent chondrocytes are found in cartilage tissue
      isolated from patients undergoing joint replacement surgery, yet their role in
      disease pathogenesis is unknown. To test the idea that SnCs might play a
      causative role in OA, we used the p16-3MR transgenic mouse, which harbors a
      p16INK4a (Cdkn2a) promoter driving the expression of a fusion protein containing
      synthetic Renilla luciferase and monomeric red fluorescent protein domains, as
      well as a truncated form of herpes simplex virus 1 thymidine kinase (HSV-TK).
      This mouse strain allowed us to selectively follow and remove SnCs after anterior
      cruciate ligament transection (ACLT). We found that SnCs accumulated in the
      articular cartilage and synovium after ACLT, and selective elimination of these
      cells attenuated the development of post-traumatic OA, reduced pain and increased
      cartilage development. Intra-articular injection of a senolytic molecule that
      selectively killed SnCs validated these results in transgenic, non-transgenic and
      aged mice. Selective removal of the SnCs from in vitro cultures of chondrocytes
      isolated from patients with OA undergoing total knee replacement decreased
      expression of senescent and inflammatory markers while also increasing expression
      of cartilage tissue extracellular matrix proteins. Collectively, these findings
      support the use of SnCs as a therapeutic target for treating degenerative joint
      disease.

PMID- 28436959
TI  - Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor
      microclustering devices.
AB  - We have shown that nanoparticles (NPs) can be used as ligand-multimerization
      platforms to activate specific cellular receptors in vivo. Nanoparticles coated
      with autoimmune disease-relevant peptide-major histocompatibility complexes
      (pMHC) blunted autoimmune responses by triggering the differentiation and
      expansion of antigen-specific regulatory T cells in vivo. Here, we define the
      engineering principles impacting biological activity, detail a synthesis process
      yielding safe and stable compounds, and visualize how these nanomedicines
      interact with cognate T cells. We find that the triggering properties of pMHC-NPs
      are a function of pMHC intermolecular distance and involve the sustained assembly
      of large antigen receptor microclusters on murine and human cognate T cells.
      These compounds show no off-target toxicity in zebrafish embryos, do not cause
      haematological, biochemical or histological abnormalities, and are rapidly
      captured by phagocytes or processed by the hepatobiliary system. This work lays
      the groundwork for the design of ligand-based NP formulations to re-program in
      vivo cellular responses using nanotechnology.

PMID- 28436960
TI  - Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron.
AB  - Iron-deficiency anaemia (IDA) is a major global public health problem. A
      sustainable and cost-effective strategy to reduce IDA is iron fortification of
      foods, but the most bioavailable fortificants cause adverse organoleptic changes
      in foods. Iron nanoparticles are a promising solution in food matrices, although
      their tendency to oxidize and rapidly aggregate in solution severely limits their
      use in fortification. Amyloid fibrils are protein aggregates initially known for
      their association with neurodegenerative disorders, but recently described in the
      context of biological functions in living organisms and emerging as unique
      biomaterial building blocks. Here, we show an original application for these
      protein fibrils as efficient carriers for iron fortification. We use
      biodegradable amyloid fibrils from beta-lactoglobulin, an inexpensive milk
      protein with natural reducing effects, as anti-oxidizing nanocarriers and
      colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms
      a stable protein-iron colloidal dispersion that undergoes rapid dissolution and
      releases iron ions during acidic and enzymatic in vitro digestion. Importantly,
      this hybrid shows high in vivo iron bioavailability, equivalent to ferrous
      sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with
      reduced organoleptic changes in foods. Feeding the rats with these hybrid
      materials did not result in abnormal iron accumulation in any organs, or changes
      in whole blood glutathione concentrations, inferring their primary safety.
      Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective
      delivery systems for iron in both solid and liquid matrices.

PMID- 28436962
TI  - Cancer immunotherapy: Making allies of phagocytes.

PMID- 28436961
TI  - The evolving landscape of drug products containing nanomaterials in the United
      States.
AB  - The Center for Drug Evaluation and Research (CDER) within the US Food and Drug
      Administration (FDA) is tracking the use of nanotechnology in drug products by
      building and interrogating a technical profile of products containing
      nanomaterials submitted to CDER. In this Analysis, data from more than 350
      products show an increase in the submissions of drug products containing
      nanomaterials over the last two decades. Of these, 65% are investigational new
      drugs, 17% are new drug applications and 18% are abbreviated new drug
      applications, with the largest class of products being liposomal formulations
      intended for cancer treatments. Approximately 80% of products have average
      particle sizes of 300 nm or lower. This analysis identifies several trends in the
      development of drug products containing nanomaterials, including the relative
      rate of approvals of these products, and provides a comprehensive overview on the
      landscape of nanotechnology application in medicine.

PMID- 28436963
TI  - A STING-activating nanovaccine for cancer immunotherapy.
AB  - The generation of tumour-specific T cells is critically important for cancer
      immunotherapy. A major challenge in achieving a robust T-cell response is the
      spatiotemporal orchestration of antigen cross-presentation in antigen-presenting
      cells with innate stimulation. Here, we report a minimalist nanovaccine,
      comprising a simple physical mixture of an antigen and a synthetic polymeric
      nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with
      low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient
      cytosolic delivery of tumour antigens to antigen-presenting cells in draining
      lymph nodes, leading to increased surface presentation while simultaneously
      activating type I interferon-stimulated genes. This effect is dependent on
      stimulator of interferon genes (STING), but not the Toll-like receptor or the
      mitochondrial antiviral-signalling protein (MAVS) pathway. The nanovaccine led to
      potent tumour growth inhibition in melanoma, colon cancer and human papilloma
      virus-E6/E7 tumour models. The combination of the PC7A nanovaccine and an anti-PD
      1 antibody showed great synergy, with 100% survival over 60 days in a TC-1 tumour
      model. Rechallenging of these tumour-free animals with TC-1 cells led to complete
      inhibition of tumour growth, suggesting the generation of long-term antitumour
      memory. The STING-activating nanovaccine offers a simple, safe and robust
      strategy in boosting anti-tumour immunity for cancer immunotherapy.

PMID- 28436964
TI  - SWELL1 is a regulator of adipocyte size, insulin signalling and glucose
      homeostasis.
AB  - Adipocytes undergo considerable volumetric expansion in the setting of obesity.
      It has been proposed that such marked increases in adipocyte size may be sensed
      via adipocyte-autonomous mechanisms to mediate size-dependent intracellular
      signalling. Here, we show that SWELL1 (LRRC8a), a member of the Leucine-Rich
      Repeat Containing protein family, is an essential component of a volume-sensitive
      ion channel (VRAC) in adipocytes. We find that SWELL1-mediated VRAC is augmented
      in hypertrophic murine and human adipocytes in the setting of obesity. SWELL1
      regulates adipocyte insulin-PI3K-AKT2-GLUT4 signalling, glucose uptake and lipid
      content via SWELL1 C-terminal leucine-rich repeat domain interactions with
      GRB2/Cav1. Silencing GRB2 in SWELL1 KO adipocytes rescues insulin-pAKT2
      signalling. In vivo, shRNA-mediated SWELL1 knockdown and adipose-targeted SWELL1
      knockout reduce adiposity and adipocyte size in obese mice while impairing
      systemic glycaemia and insulin sensitivity. These studies identify SWELL1 as a
      cell-autonomous sensor of adipocyte size that regulates adipocyte growth, insulin
      sensitivity and glucose tolerance.

PMID- 28436965
TI  - A three-dimensional model of human lung development and disease from pluripotent
      stem cells.
AB  - Recapitulation of lung development from human pluripotent stem cells (hPSCs) in
      three dimensions (3D) would allow deeper insight into human development, as well
      as the development of innovative strategies for disease modelling, drug discovery
      and regenerative medicine. We report here the generation from hPSCs of lung bud
      organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into
      branching airway and early alveolar structures after xenotransplantation and in
      Matrigel 3D culture. Expression analysis and structural features indicated that
      the branching structures reached the second trimester of human gestation.
      Infection in vitro with respiratory syncytial virus, which causes small airway
      obstruction and bronchiolitis in infants, led to swelling, detachment and
      shedding of infected cells into the organoid lumens, similar to what has been
      observed in human lungs. Introduction of mutation in HPS1, which causes an early
      onset form of intractable pulmonary fibrosis, led to accumulation of
      extracellular matrix and mesenchymal cells, suggesting the potential use of this
      model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate
      lung development and may provide a useful tool to model lung disease.

PMID- 28436966
TI  - Microbial metabolites regulate host lipid metabolism through NR5A-Hedgehog
      signalling.
AB  - Microorganisms and their hosts share the same environment, and microbial
      metabolic molecules (metabolites) exert crucial effects on host physiology.
      Environmental factors not only shape the composition of the host's resident
      microorganisms, but also modulate their metabolism. However, the exact molecular
      relationship among the environment, microbial metabolites and host metabolism
      remains largely unknown. Here, we discovered that environmental methionine tunes
      bacterial methyl metabolism to regulate host mitochondrial dynamics and lipid
      metabolism in Caenorhabditis elegans through an endocrine crosstalk involving
      NR5A nuclear receptor and Hedgehog signalling. We discovered that methionine
      deficiency in bacterial medium decreases the production of bacterial metabolites
      that are essential for phosphatidylcholine synthesis in C. elegans. Reductions of
      diundecanoyl and dilauroyl phosphatidylcholines attenuate NHR-25, a NR5A nuclear
      receptor, and release its transcriptional suppression of GRL-21, a Hedgehog-like
      protein. The induction of GRL-21 consequently inhibits the PTR-24 Patched
      receptor cell non-autonomously, resulting in mitochondrial fragmentation and
      lipid accumulation. Together, our work reveals an environment-microorganism-host
      metabolic axis regulating host mitochondrial dynamics and lipid metabolism, and
      discovers NR5A-Hedgehog intercellular signalling that controls these metabolic
      responses with critical consequences for host health and survival.

PMID- 28436967
TI  - Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex.
AB  - ASPM (known as Asp in fly and ASPM-1 in worm) is a microcephaly-associated
      protein family that regulates spindle architecture, but the underlying mechanism
      is poorly understood. Here, we show that ASPM forms a complex with another
      protein linked to microcephaly, the microtubule-severing ATPase katanin. ASPM and
      katanin localize to spindle poles in a mutually dependent manner and regulate
      spindle flux. X-ray crystallography revealed that the heterodimer formed by the N
      and C-terminal domains of the katanin subunits p60 and p80, respectively, binds
      conserved motifs in ASPM. Reconstitution experiments demonstrated that ASPM
      autonomously tracks growing microtubule minus ends and inhibits their growth,
      while katanin decorates and bends both ends of dynamic microtubules and
      potentiates the minus-end blocking activity of ASPM. ASPM also binds along
      microtubules, recruits katanin and promotes katanin-mediated severing of dynamic
      microtubules. We propose that the ASPM-katanin complex controls microtubule
      disassembly at spindle poles and that misregulation of this process can lead to
      microcephaly.

PMID- 28436968
TI  - Metabolic control of primed human pluripotent stem cell fate and function by the
      miR-200c-SIRT2 axis.
AB  - A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation
      (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which
      is also observed in primed human pluripotent stem cells (hPSCs). Here, we report
      that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature
      of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming
      during induced pluripotency by targeting glycolytic enzymes including aldolase,
      glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase.
      Remarkably, knockdown of SIRT2 in human fibroblasts resulted in significantly
      decreased OXPHOS and increased glycolysis. In addition, we found that miR-200c-5p
      specifically targets SIRT2, downregulating its expression. Furthermore, SIRT2
      overexpression in hPSCs significantly affected energy metabolism, altering stem
      cell functions such as pluripotent differentiation properties. Taken together,
      our results identify the miR-200c-SIRT2 axis as a key regulator of metabolic
      reprogramming (Warburg-like effect), via regulation of glycolytic enzymes, during
      human induced pluripotency and pluripotent stem cell function.

PMID- 28436969
TI  - Associations between levels of insulin-like growth factor 1 and sinusoidal
      obstruction syndrome after allogeneic haematopoietic stem cell transplantation.
AB  - Allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) is
      challenged by severe adverse events, as cytotoxic effects of the conditioning may
      result in systemic inflammation, leaky epithelial barriers and organ toxicities,
      contributing to treatment-related morbidity and mortality. We hypothesised that
      insulin-like growth factor-1 (IGF-1), a mediator of growth and proliferation of
      various tissues, may attenuate chemotherapy-induced tissue damage after HSCT. We
      prospectively measured plasma levels of IGF-1 and its binding protein 3 (IGFBP-3)
      in 41 patients undergoing myeloablative HSCT. IGF-1 and IGFBP-3 levels were
      inversely correlated with C-reactive protein and interleukin-6 levels post HSCT.
      In multivariate analyses, low levels of IGF-1 and IGFBP-3 before conditioning
      were associated with increased risk of developing sinusoidal obstruction syndrome
      (SOS; OR=5.00 per 1 SDS decrease in IGF-1 (95% CI: 1.45-16.67), P=0.011 and
      OR=5.00 (1.37-20.00), P=0.015, respectively). Furthermore, low pre-transplant
      levels of IGF-1 and IGFBP-3 were associated with increased fluid retention during
      the first 21 days post transplant (OR=7.69 (95% CI: 1.59-33.33), P=0.012, and
      OR=2.94 (1.03-8.33), P=0.045). These data suggest that high levels of IGF-1 and
      IGFBP-3 may have a protective effect against fluid retention and SOS, possibly by
      attenuating systemic inflammation, and may prove useful as predictive biomarkers
      of SOS.

PMID- 28436970
TI  - Unconditioned unrelated donor bone marrow transplantation for IL7Ralpha- and
      Artemis-deficient SCID.

PMID- 28436971
TI  - When selecting a cord blood unit from a firstborn donor verify that the patient
      shares an Ag with the unit that is foreign to the mother of the donor.

PMID- 28436972
TI  - Allogeneic transplantation in primary refractory AML.

PMID- 28436973
TI  - A review of hematopoietic cell transplantation in China: data and trends during
      2008-2016.
AB  - Hematopoietic cell transplantation (HCT) activity in China was surveyed to assess
      its current status. A record number of HCTs (21 884: 16 631 allogeneic (76%) and
      5253 autologous (24%)) were reported by 76 centers in China between 1 January
      2008 and 30 June 2016. HCT trends included continued growth in transplant
      activity, a continued rapid increase in haploidentical donors (HID), and slower
      growth for unrelated donors, matched-related donors (MRD) and cord blood
      transplantation (CBT). The proportion of HID HCT among allogeneic HCTs increased
      from 29.6% (313/1062) in 2008 to 48.8% (1939/3975) in 2015, even 51.7%
      (1157/2237) in the first half of 2016. During this time frame, the proportion of
      MRD HCTs among allogeneic HCTs decreased from 48.1% (511/1062) to 33.0%
      (332/3975). The proportion of unrelated donor HCTs among allogeneic HCTs
      decreased from 20.4 (216/1062) to 13.6% (540/3975). The proportion of CBTs among
      allogeneic HCTs was increased from 2.1% (22/1062) to 4.2% (184/3975). HCTs have
      been increasing continuously for all indications except chronic myelogenous
      leukemia. Severe aplastic anemia is a common HCT indication among non-malignant
      diseases in China. The number of cases of allogeneic HCT for this disorder has
      increased annually, from 59 (5.6%) in 2008 to 569 (14.3%) in 2015, even 334
      (14.9%) in the first half year in 2016. This survey clearly shows recent trends
      for HCTs in China.

PMID- 28436975
TI  - Haploidentical stem cell transplantation with CD3+-/CD19+- depleted peripheral
      stem cells for patients with advanced stage sickle cell disease and no
      alternative donor: results of a pilot study.

PMID- 28436974
TI  - High-dose thiotepa-based chemotherapy with autologous stem cell support in
      elderly patients with primary central nervous system lymphoma: a European
      retrospective study.
AB  - In this retrospective multicentre study, we investigated the outcomes of elderly
      primary central nervous system lymphoma (PCNSL) patients (?65 years) who
      underwent high-dose chemotherapy followed by autologous stem cell transplantation
      (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission,
      progression-free survival (PFS), overall survival (OS) and treatment-related
      mortality. We identified 52 patients (median age 68.5 years, median Karnofsky
      Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT
      ASCT. Fifteen patients (28.8%) received HDT-ASCT as first-line treatment and 37
      (71.2%) received it as second or subsequent line. Remission status before HDT
      ASCT was: CR 34.6%, PR 51.9%, stable disease 3.8% and progressive disease 9.6%.
      Following completion of HDT-ASCT, 36 patients (69.2%) achieved CR (21.2% first
      line setting and 48.1% second or subsequent line setting) and 9 (17.3%) PR (5.8%
      first-line setting and 11.5% second or subsequent line setting). With a median
      follow-up of 22 months after HDT-ASCT, median PFS and OS were reached after 51.1
      and 122.3 months, respectively. The 2-year PFS and OS rates were 62.0% and 70.8%,
      respectively. We observed two HDT-ASCT-associated deaths (3.8%). In selected
      elderly PCNSL patients, HDT-ASCT, using thiotepa-based conditioning regimes, is
      feasible and effective. Further prospective and comparative studies are warranted
      to further evaluate the role of HDT-ASCT in elderly PCNSL patients.

PMID- 28436976
TI  - RBC depletion from a PBSC graft.

PMID- 28436977
TI  - Provision of long-term monitoring and late effects services following adult
      allogeneic haematopoietic stem cell transplant: a survey of UK NHS-based
      programmes.
AB  - Despite international guidelines, optimal delivery models of late effects (LE)
      services for HSCT patients are unclear from the clinical, organizational and
      economic viewpoints. To scope current LE service delivery models within the UK
      NHS (National Health Service), in 2014, we surveyed the 27 adult allogeneic HSCT
      centres using a 30-question online tool, achieving a 100% response rate. Most LE
      services were led and delivered by senior physicians (>80% centres). Follow-up
      was usually provided in a dedicated allograft or LE clinic for the first year
      (>90% centres), but thereafter attrition meant that only ~50% of patients were
      followed after 5 years. Most centres (69%) had a standard operating procedure for
      long-term monitoring but access to a LE Multi-Disciplinary Team was rare (19%
      centres). Access to medical specialities necessary for LE management was good,
      but specialist interest in long-term HSCT complications was uncommon. Some
      screening (endocrinopathy, cardiovascular) was near universal, but other areas
      were more limited (mammography, cervical smears). Funding of extra staff and
      investigations were the most commonly perceived barriers to implementation of LE
      services. This survey shows variation in the long-term follow-up of allogeneic
      HSCT survivors within the UK NHS and further work is warranted to optimize
      effective, sustainable and affordable models of LE service delivery among this
      group.

PMID- 28436978
TI  - Association of hematopoietic cell transplantation-specific comorbidity index with
      resource utilization after allogeneic transplantation.
AB  - Comorbidities affect clinical outcomes and costs in medicine. The hematopoietic
      cell transplantation (HCT)-specific comorbidity index (HCT-CI) predicts mortality
      risk after HCT. Its association with resource utilization (RU) is unknown. In
      this single-center, retrospective study, we examined the association of HCT-CI
      with RU (readmissions, length of hospital stay (LOS) and days out of hospital
      alive (DOHA)) in first 100 days (n=328) and 1 year (n=226) in allogeneic HCT
      patients from January 2010 to June 2014. Age, disease risk, conditioning and use
      of antithymocyte globulin were significantly different in the four groups with
      HCT-CI 0 to1 (n=138), 2 (n=56), 3 (n=55) or ?4 (n=79). Although the readmissions
      were higher in the first 100 days for patients with HCT-CI >0-1 (P=0.03), they
      were not significantly different in patients over 1 year (P=0.13). In the
      multivariable analysis, patients with HCT-CI score of >0 to 1 had increased LOS
      and fewer DOHA in both 100 days and 1 year after HCT. In this exploratory
      analysis, we found that HCT-CI >0 to 1 is associated with increased RU after
      allogeneic HCT. Recognizing predictors of RU can identify patients at risk of
      high utilization and help understand what drives health-care costs.

PMID- 28436979
TI  - Successful chimeric Ag receptor modified T cell therapy for isolated testicular
      relapse after hematopoietic cell transplantation in an acute lymphoblastic
      leukemia patient.

PMID- 28436980
TI  - Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of
      reward and punishment.
AB  - Orchestrating appropriate behavioral responses in the face of competing signals
      that predict either rewards or threats in the environment is crucial for
      survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial
      prefrontal cortex have been implicated in reward-seeking and fear-related
      responses, but how information flows between these reciprocally connected
      structures to coordinate behavior is unknown. We recorded neuronal activity from
      the BLA and PL while rats performed a task wherein competing shock- and sucrose
      predictive cues were simultaneously presented. The correlated firing primarily
      displayed a BLA->PL directionality during the shock-associated cue. Furthermore,
      BLA neurons optogenetically identified as projecting to PL more accurately
      predicted behavioral responses during competition than unidentified BLA neurons.
      Finally photostimulation of the BLA->PL projection increased freezing, whereas
      both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA
      >PL circuit is critical in governing the selection of behavioral responses in the
      face of competing signals.

PMID- 28436981
TI  - Identification of spinal circuits involved in touch-evoked dynamic mechanical
      pain.
AB  - Mechanical hypersensitivity is a debilitating symptom for millions of chronic
      pain patients. It exists in distinct forms, including brush-evoked dynamic and
      filament-evoked punctate hypersensitivities. We reduced dynamic mechanical
      hypersensitivity induced by nerve injury or inflammation in mice by ablating a
      group of adult spinal neurons defined by developmental co-expression of VGLUT3
      and Lbx1 (VT3Lbx1 neurons): the mice lost brush-evoked nocifensive responses and
      conditional place aversion. Electrophysiological recordings show that VT3Lbx1
      neurons form morphine-resistant polysynaptic pathways relaying inputs from low
      threshold Abeta mechanoreceptors to lamina I output neurons. The subset of
      somatostatin-lineage neurons preserved in VT3Lbx1-neuron-ablated mice is largely
      sufficient to mediate morphine-sensitive and morphine-resistant forms of von Frey
      filament-evoked punctate mechanical hypersensitivity. Furthermore, acute
      silencing of VT3Lbx1 neurons attenuated pre-established dynamic mechanical
      hypersensitivity induced by nerve injury, suggesting that these neurons may be a
      cellular target for treating this form of neuropathic pain.

PMID- 28436982
TI  - Delay activity of specific prefrontal interneuron subtypes modulates memory
      guided behavior.
AB  - Memory-guided behavior requires maintenance of task-relevant information without
      sensory input, but the underlying circuit mechanism remains unclear. Calcium
      imaging in mice performing a delayed Go or No-Go task revealed robust delay
      activity in dorsomedial prefrontal cortex, with different pyramidal neurons
      signaling Go and No-Go action plans. Inhibiting pyramidal neurons by
      optogenetically activating somatostatin- or parvalbumin-positive interneurons,
      even transiently during the delay, impaired task performance, primarily by
      increasing inappropriate Go responses. In contrast, activating vasoactive
      intestinal peptide (VIP)-positive interneurons enhanced behavioral performance
      and neuronal action plan representation. Furthermore, while endogenous activity
      of somatostatin and parvalbumin neurons was strongly biased toward Go trials, VIP
      neurons were similarly active in Go and No-Go trials. Somatostatin or VIP neuron
      activation also impaired or enhanced performance, respectively, in a delayed two
      alternative forced-choice task. Thus, dorsomedial prefrontal cortex is a crucial
      component of the short-term memory network, and activation of its VIP neurons
      improves memory retention.

PMID- 28436983
TI  - Stable Polycomb-dependent transgenerational inheritance of chromatin states in
      Drosophila.
AB  - Transgenerational epigenetic inheritance (TEI) describes the transmission of
      alternative functional states through multiple generations in the presence of the
      same genomic DNA sequence. Very little is known about the principles and the
      molecular mechanisms governing this type of inheritance. Here, by transiently
      enhancing 3D chromatin interactions, we established stable and isogenic
      Drosophila epilines that carry alternative epialleles, as defined by differential
      levels of Polycomb-dependent trimethylation of histone H3 Lys27 (forming
      H3K27me3). After being established, epialleles can be dominantly transmitted to
      naive flies and can induce paramutation. Importantly, epilines can be reset to a
      naive state by disruption of chromatin interactions. Finally, we found that
      environmental changes modulate the expressivity of the epialleles, and we
      extended our paradigm to naturally occurring phenotypes. Our work sheds light on
      how nuclear organization and Polycomb group (PcG) proteins contribute to
      epigenetically inheritable phenotypic variability.

PMID- 28436986
TI  - Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple
      loci.
AB  - Complex traits arise from the interplay between genetic and environmental
      factors. The actions of these factors usually appear to be additive, and few
      compelling examples of gene-environment synergy have been documented. Here we
      show that adiposity significantly amplifies the effect of three sequence variants
      (encoding PNPLA3 p.I148M, TM6SF2 p.E167K, and GCKR p.P446L) associated with
      nonalcoholic fatty liver disease (NAFLD). Synergy between adiposity and genotype
      promoted the full spectrum of NAFLD, from steatosis to hepatic inflammation to
      cirrhosis. We found no evidence of strong interaction between adiposity and
      sequence variants influencing other adiposity-associated traits. These results
      indicate that adiposity augments genetic risk of NAFLD at multiple loci that
      confer susceptibility to hepatic steatosis through diverse metabolic mechanisms.

PMID- 28436988
TI  - Erratum: Pre-conception and prenatal alcohol exposure from mothers and fathers
      drinking and head circumference: results from the Norwegian Mother-Child Study
      (MoBa).

PMID- 28436987
TI  - Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer
      histotypes.
AB  - We studied the whole-genome point mutation and structural variation patterns of
      133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid
      (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in
      ovarian cancer. Ab initio clustering of integrated point mutation and structural
      variation signatures identified seven subgroups both between and within
      histotypes. Prevalence of foldback inversions identified a prognostically
      significant HGSC group associated with inferior survival. This finding was
      recapitulated in two independent cohorts (n = 576 cases), transcending BRCA1 and
      BRCA2 mutation and gene expression features of HGSC. CCOC cancers grouped
      according to APOBEC deamination (26%) and age-related mutational signatures
      (40%). ENOCs were divided by cases with microsatellite instability (28%), with a
      distinct mismatch-repair mutation signature. Taken together, our work establishes
      the potency of the somatic genome, reflective of diverse DNA repair deficiencies,
      to stratify ovarian cancers into distinct biological strata within the major
      histotypes.

PMID- 28436989
TI  - Corrigendum: The clinically approved antiviral drug sofosbuvir inhibits Zika
      virus replication.

PMID- 28436985
TI  - Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in
      myeloid leukemia stem cells.
AB  - The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells
      remains poorly characterized. The MSI2 RBP is a central regulator of translation
      of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting
      RBP network and functional shRNA screening, we identified 24 genes required for
      in vivo leukemia. Syncrip was the most differentially required gene between
      normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and
      differentiation while delaying leukemogenesis. Gene expression profiling of
      SYNCRIP-depleted cells demonstrated a loss of the MLL and HOXA9 leukemia stem
      cell program. SYNCRIP and MSI2 interact indirectly though shared mRNA targets.
      SYNCRIP maintains HOXA9 translation, and MSI2 or HOXA9 overexpression rescued the
      effects of SYNCRIP depletion. Altogether, our data identify SYNCRIP as a new RBP
      that controls the myeloid leukemia stem cell program. We propose that targeting
      these RBP complexes might provide a novel therapeutic strategy in leukemia.

PMID- 28436990
TI  - TCRP1 promotes NIH/3T3 cell transformation by over-activating PDK1 and AKT1.
AB  - Tongue cancer resistance-related protein 1 (TCRP1) gene was first cloned from the
      multidrug resistance tongue cancer cell (Tca8113/pingyangmycin) in our lab. Our
      precious studies demonstrated that TCRP1 was involving in chemotherapy and
      radiotherapy resistance of tongue cancer cells, lung cancer cells and ovarian
      cancer cells. In this study, we showed that TCRP1 overexpression promotes cell
      transformation and tumorigenesis through hyperphosphorylation of the oncogenic
      kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT1, whereas
      inhibition of PDK1 by OSU-03012 or PDK1 small interfering RNA reversed TCRP1
      mediated cell transformation. Importantly, TCRP1 was able to directly interact
      with PDK1, and 93-107 amino-acid and 109-124 amino-acid sites of TCRP1 were the
      common binding domain of PDK1. Moreover, in line with its oncogenic activity, we
      found that TCRP1 is often overexpressed in human in lung cancer, glioma, ovarian
      cancer, thyroid cancer, nasopharyngeal carcinoma, pancreatic cancer, stomach
      cancer and tongue carcinoma tissues. Spearman correlation analysis showed that
      the expression of TCRP1 has a positive correlation with p-PDK1, as well as p-AKT1
      in lung cancer and gliomas tissues. Thus, TCRP1 may be a candidate as human
      oncoprotein that promotes cancer development by activation of PDK1/AKT1
      signaling.

PMID- 28436992
TI  - Corrigendum: KANK1 inhibits cell growth by inducing apoptosis through regulating
      CXXC5 in human malignant peripheral nerve sheath tumors.

PMID- 28436993
TI  - Corrigendum: Putative WRKYs associated with regulation of fruit ripening revealed
      by detailed expression analysis of the WRKY gene family in pepper.

PMID- 28436994
TI  - Erratum: Influence of substrate modulus on gecko adhesion.

PMID- 28436991
TI  - CRB3 downregulation confers breast cancer stem cell traits through TAZ/beta
      catenin.
AB  - The cancer stem cell (CSC) theory depicts a special population within the cancer
      mass that self-renew and sustain the cancer, even if the other cells were
      eliminated by therapies. How CSCs acquire these unique traits is still unclear.
      Crumbs homolog 3 (CRB3), a member of the CRB polarity complex, has been reported
      to act as a tumor suppressor. Here, we detected significantly lower or negative
      CRB3 expression in human breast cancer tissues. Knockdown of CRB3 generated non
      tumorigenic, immortalized breast epithelial cell line MCF 10A with CSC
      properties. Simultaneously, we found that CRB3 downregulation induced the
      epithelial-mesenchymal transition and activated TAZ (transcriptional co-activator
      with PDZ-binding motif) and beta-catenin. Significantly, the activation of TAZ
      and beta-catenin sufficed in conferring MCF 10A cells with CSC properties. This
      study demonstrates that cell polarity proteins may serve as a switch of the
      differentiated vs multipotent states in breast cancers.

PMID- 28436995
TI  - Faking death to avoid male coercion: extreme sexual conflict resolution in a
      dragonfly.

PMID- 28436996
TI  - Continuum Electrostatic Calculation on Bovine Rhodopsin: Protonation and the
      Effect of the Membrane Potential.
AB  - In this work, we calculate the protonation probabilities of titratable residues
      of bovine rhodopsin using the Poisson-Boltzmann equation. We also consider the
      influence of the membrane potential. Our results indicate that at physiological
      pH, the titratable groups directly involved in photosensing, namely Glu113,
      Glu181 and the retinal Schiff base, are charged. In contrast, the residues Asp83,
      Glu122 and His211, which are buried in the membrane, are uncharged. However, as
      these later residues are localized in the middle of the membrane, they are
      exposed to the membrane potential more strongly, which may have important
      functional implications. Despite of their large distance, Asp83 and Glu122
      interact relatively strongly. As these two residues are in contact with opposite
      sides of the membrane, the membrane potential has different effects on them,
      which allows an enhancement of the membrane potential signal. An analysis of the
      different contributions to the protonation energy indicates that conformational
      changes that reduce the desolvation penalty of Asp83, Glu122 and His211 may lead
      to a complex protonation pattern change that allows an influence of the membrane
      potential on the function of rhodopsin. The high degree of evolutionary
      conservation of these three buried residues supports the idea of their functional
      importance. Our results are in-line with many experimental findings and lead to
      new ideas that can be experimentally tested.

PMID- 28436997
TI  - Truncating mutations on myofibrillar myopathies causing genes as prevalent
      molecular explanations on patients with dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with
      high morbidity and mortality. More than 40 genes have been reported to cause DCM.
      To provide new insights into the pathophysiology of dilated cardiomyopathy, a
      next-generation sequencing (NGS) workflow based on a panel of 48 cardiomyopathies
      causing genes was used to analyze a cohort of 222 DCM patients. Truncating
      variants were detected on 63 unrelated DCM cases (28.4%). Most of them were
      identified, as expected, on TTN (29 DCM probands), but truncating variants were
      also identified on myofibrillar myopathies causing genes in 17 DCM patients (7.7%
      of the DCM cohort): 10 variations on FLNC and 7 variations on BAG3 . This study
      confirms that truncating variants on myofibrillar myopathies causing genes are
      frequently associated with dilated cardiomyopathies and also suggest that FLNC
      mutations could be considered as a common cause of dilated cardiomyopathy.
      Molecular approaches that would allow to detect systematically truncating
      variants in FLNC and BAG3 into genetic testing should significantly increase test
      sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for
      many patients with dilated cardiomyopathy.

PMID- 28436984
TI  - Genomic analyses identify hundreds of variants associated with age at menarche
      and support a role for puberty timing in cancer risk.
AB  - The timing of puberty is a highly polygenic childhood trait that is
      epidemiologically associated with various adult diseases. Using 1000 Genomes
      Project-imputed genotype data in up to ~370,000 women, we identify 389
      independent signals (P < 5 * 10-8) for age at menarche, a milestone in female
      pubertal development. In Icelandic data, these signals explain ~7.4% of the
      population variance in age at menarche, corresponding to ~25% of the estimated
      heritability. We implicate ~250 genes via coding variation or associated
      expression, demonstrating significant enrichment in neural tissues. Rare variants
      near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects
      when paternally inherited. Mendelian randomization analyses suggest causal
      inverse associations, independent of body mass index (BMI), between puberty
      timing and risks for breast and endometrial cancers in women and prostate cancer
      in men. In aggregate, our findings highlight the complexity of the genetic
      regulation of puberty timing and support causal links with cancer susceptibility.

PMID- 28436998
TI  - Swedish women's perceptions of and conformity to feminine norms.
AB  - The relatively high gender equality in the Swedish society is likely to exert an
      influence on gender role construction. Hence, the present research aimed to
      investigate Swedish women's perceptions of and conformity to feminine norms. A
      mixed methods approach with two studies was used. In Study 1, young Swedish
      women's gender role conformity, as measured by the Conformity to Feminine Norms
      Inventory 45 (CFNI-45), was compared to the results from previously published
      studies in Canada, the United States, and Slovakia. Overall, Swedish women
      displayed less conformity than their foreign counterparts, with the largest
      difference on the subscale Sexual fidelity. In Study 2, focus group interviews
      with young Swedish women added a more complex picture of feminine norms in the
      Swedish society. For instance the results indicated that Swedish women, while
      living in a society with a strong gender equality discourse, are torn between the
      perceived need to invest in their appearances and the risk of being viewed as non
      equal when doing so. In sum, despite the fact that traditional gender roles are
      less pronounced in Sweden, gender role conformity is still a pressing issue.
      Since attending to the potential roles of feminine norms in women's lives
      previously has been proposed to be useful in counseling and therapeutic work, the
      present research also offers valuable information for both researchers and
      practitioners. [Correction added on 5 May 2017, after first online publication in
      April 2017: An incorrect Abstract was inadvertently captured in the published
      article and has been corrected in this current version.].

PMID- 28437000
TI  - Magnetically guided capsule endoscopy.
AB  - Wireless capsule endoscopy (WCE) is a powerful tool for medical screening and
      diagnosis, where a small capsule is swallowed and moved by means of natural
      peristalsis and gravity through the human gastrointestinal (GI) tract. The camera
      integrated capsule allows for visualization of the small intestine, a region
      which was previously inaccessible to classical flexible endoscopy. As a
      diagnostic tool, it allows to localize the sources of bleedings in the middle
      part of the gastrointestinal tract and to identify diseases, such as inflammatory
      bowel disease (Crohn's disease), polyposis syndrome, and tumors. The screening
      and diagnostic efficacy of the WCE, especially in the stomach region, is hampered
      by a variety of technical challenges like the lack of active capsular position
      and orientation control. Therapeutic functionality is absent in most commercial
      capsules, due to constraints in capsular volume and energy storage. The
      possibility of using body-exogenous magnetic fields to guide, orient, power, and
      operate the capsule and its mechanisms has led to increasing research in
      Magnetically Guided Capsule Endoscopy (MGCE). This work shortly reviews the
      history and state-of-art in WCE technology. It highlights the magnetic
      technologies for advancing diagnostic and therapeutic functionalities of WCE. Not
      restricting itself to the GI tract, the review further investigates the
      technological developments in magnetically guided microrobots that can navigate
      through the various air- and fluid-filled lumina and cavities in the body for
      minimally invasive medicine.

PMID- 28437002
TI  - Dentists' restorative decision-making and implications for an 'amalgamless'
      profession. Part 4: clinical factor.
AB  - BACKGROUND: The Minamata Convention embodies a worldwide reduction in the
      production and use of mercury and mercury-containing products and processes,
      including a phase-down of dental amalgam. This will change the approach to the
      use of direct restorative materials in the near future. There is little research
      as to the influence of clinical factors on dentists' decision-making which may be
      of use when determining the impact of any change. METHODS: An online survey
      relating to aspects of and attitudes to the use of direct restorative materials
      was distributed to all dentists who were members of the Australian Dental
      Association and/or members or fellows of the Royal Australasian College of Dental
      Surgeons. Data were statistically analysed. RESULTS: There were 408 respondents
      to the survey. Eighty-seven per cent of respondents (strongly) disagreed that
      amalgam was a technically more difficult material to place compared with resin
      composite, 82% (strongly) disagreed that placement time for amalgam was longer
      than that for resin composite and 69% (strongly) disagreed that amalgam was more
      difficult to finish than resin composite. Eighty-three per cent of respondents
      stated they were confident in their ability to place amalgam restorations. Where
      physical properties were of importance, indirect restorations were preferred
      (e.g. parafunction) 54%. The factors considered most important when choosing a
      direct restorative material included moisture control and aesthetics; least
      important factors were cost and time to place. CONCLUSIONS: There is consensus
      that amalgam is not more technically difficult to use, place or finish than resin
      composite and vice versa. There is recognition that both amalgam and resin
      composite have limitations in terms of physical properties. When choosing a
      direct restorative material, clinical factors considered to be of greatest
      importance are moisture control, aesthetics and the need to apply minimally
      invasive approaches. There is little difference in the opinions of users and non
      users of amalgam with respect to these findings.

PMID- 28437003
TI  - High intensity focused ultrasound for the treatment of adenomyosis: selection
      criteria, efficacy, safety and fertility.
AB  - Adenomyosis is a disorder of uterus in which endometrial glands and stroma are
      present within the uterine musculature. The main clinical manifestations are
      dysmenorrhea and menorrhagia. Adenomyosis has a great impact on both the quality
      of life and fertility of women. The treatment of adenomyosis remains an immense
      challenge. Relevant articles were searched through MEDLINE and PubMed between
      2000 and March 2017. The search terms of adenomyosis, magnetic resonance imaging
      (MRI) features of adenomyosis, high intensity focused ultrasound (HIFU),
      ultrasound-guided HIFU and MRgFUS were used. There were no language restrictions.
      HIFU is a non-invasive local thermal ablation technique which has been used in
      the treatment of both focal and diffuse adenomyosis. Several case studies have
      demonstrated that HIFU presents low rate of minor and/or major complications and,
      at the same time, a long symptom-relief period. Multiple factors such as the
      enhancement type of the adenomyotic lesion, volume of the adenomyotic lesions,
      number of hyperintense foci on T2WI, location of the uterus, location of
      adenomyotic lesions, thickness of the abdominal wall and distance from the skin
      to the adenomyotic lesions contribute to the efficacy of HIFU. Consequently,
      based on these contributing factors, specific and strict selection criteria have
      been used to achieve higher efficacy. Thus, patients with pelvic endometriosis,
      adhesions between the bowel and the uterus, or an abdominal surgical scar wider
      than 10 mm, are not suitable for HIFU treatment. Moreover, HIFU-treated patients
      with adenomyosis, who wished to conceive, showed high conception and live birth
      rates. HIFU is a new and promising treatment option for patients with
      adenomyosis, but its efficacy, safety, cost-effectiveness and fertility outcome
      must be evaluated by randomized controlled trials.

PMID- 28437001
TI  - Tumour-associated changes in intestinal epithelial cells cause local accumulation
      of KLRG1+ GATA3+ regulatory T cells in mice.
AB  - CD4+ Foxp3+ regulatory T (Treg) cells include differentiated populations of
      effector Treg cells characterized by the expression of specific transcription
      factors. Tumours, including intestinal malignancies, often present with local
      accumulation of Treg cells that can prevent tumour clearance, but how tumour
      progression leads to Treg cell accumulation is incompletely understood. Here
      using genetically modified mouse models we show that ablation of E-cadherin, a
      process associated with epithelial to mesenchymal transition and tumour
      progression, promotes the accumulation of intestinal Treg cells by the specific
      accumulation of the KLRG1+ GATA3+ Treg subset. Epithelial E-cadherin ablation
      activates the beta-catenin pathway, and we find that increasing beta-catenin
      signals in intestinal epithelial cells also boosts Treg cell frequencies through
      local accumulation of KLRG1+ GATA3+ Treg cells. Both E-cadherin ablation and
      increased beta-catenin signals resulted in epithelial cells with higher levels of
      interleukin-33, a cytokine that preferentially expands KLRG1+ GATA3+ Treg cells.
      Tumours often present reduced E-cadherin expression and increased beta-catenin
      signalling and interleukin-33 production. Accordingly, Treg cell accumulation in
      intestinal tumours from APCmin/+ mice was exclusively due to the increase in
      KLRG1+ GATA3+ Treg cells. Our data identify a novel axis through which epithelial
      cells control local Treg cell subsets, which may be activated during intestinal
      tumorigenesis.

PMID- 28437004
TI  - 4,4'-Dichlorodiphenyltrichloroethane (DDT) and 4,4'
      dichlorodiphenyldichloroethylene (DDE) inhibit myogenesis in C2C12 myoblasts.
AB  - BACKGROUND: Most countries have banned the use of 4,4'
      dichlorodiphenyltrichloroethane (DDT). However, owing to its extremely high
      lipophilic characteristics, DDT and its metabolite 4,4'
      dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and in
      many types of food. The positive correlation between exposure to insecticides,
      including DDT and DDE, and weight gain, resulting in impaired energy metabolism
      in offspring following perinatal DDT and DDE exposure, was previously reported.
      Therefore the influence of DDT and DDE on myogenesis using C2C12 myoblasts was
      investigated in this study. RESULTS: DDT and DDE decreased myotube formation dose
      and time-dependently. Among myogenic regulatory factors, DDT and DDE mainly
      decreased MyoD1 and Myf5 expression. DDT and DDE treatment also altered Myostatin
      expression, phosphorylation of protein kinase B, p70 ribosomal protein S6 kinase,
      forkhead box O protein 3 and mammalian target of rapamycin, resulting in
      attenuation of myotube formation. CONCLUSION: These results may have significant
      implications for understanding the effects of developmental exposure of DDT and
      DDE on myogenesis and development of obesity and type 2 diabetes later in life.
      (c) 2017 Society of Chemical Industry.

PMID- 28437006
TI  - Prognosis and risk assessment in AL amyloidosis - There and back again.

PMID- 28437007
TI  - Simulating Biomolecules: Festschrift to commemorate the 60th birthday of Charles
      L. Brooks III.

PMID- 28437005
TI  - Convergent ERK1/2, p38 and JNK mitogen activated protein kinases (MAPKs)
      signalling mediate catecholoestradiol-induced proliferation of ovine uterine
      artery endothelial cells.
AB  - KEY POINTS: The catechol metabolites of 17beta-oestradiol (E2 beta), 2
      hydroxyoestradiol (2-OHE2 ) and 4-hydroxyoestradiol (4-OHE2 ), stimulate
      proliferation of pregnancy-derived ovine uterine artery endothelial cells (P
      UAECs) through beta-adrenoceptors (beta-ARs) and independently of the classic
      oestrogen receptors (ERs). Herein we show that activation of ERK1/2, p38 and JNK
      mitogen activated protein kinases (MAPKs) is necessary for 2-OHE2 - and 4-OHE2 
      induced P-UAEC proliferation, as well as proliferation induced by the parent
      hormone E2 beta and other beta-AR signalling hormones (i.e. catecholamines).
      Conversely, although 2-OHE2 and 4-OHE2 rapidly activate phosphatidylinositol 3
      kinase (PI3K), its activation is not involved in catecholoestradiol-induced P
      UAEC proliferation. We also show for the first time the signalling mechanisms
      involved in catecholoestradiol-induced P-UAEC proliferation; which converge at
      the level of MAPKs with the signalling mechanisms mediating E2 beta- and
      catecholamine-induced proliferation. The present study advances our understanding
      of the complex signalling mechanisms involved in regulating uterine endothelial
      cell proliferation during pregnancy. ABSTRACT: Previously we demonstrated that
      the biologically active metabolites of 17beta-oestradiol, 2-hydroxyoestradiol (2
      OHE2 ) and 4-hydroxyoestradiol (4-OHE2 ), stimulate pregnancy-specific
      proliferation of uterine artery endothelial cells derived from pregnant (P
      UAECs), but not non-pregnant ewes. However, unlike 17beta-oestradiol, which
      induces proliferation via oestrogen receptor-beta (ER-beta), the
      catecholoestradiols mediate P-UAEC proliferation via beta-adrenoceptors (beta-AR)
      and independently of classic oestrogen receptors. Herein, we aim to further
      elucidate the signalling mechanisms involved in proliferation induced by
      catecholoestradiols in P-UAECs. P-UAECs were treated with 2-OHE2 and 4-OHE2 for
      0, 0.25, 0.5, 1, 2, 4, 12 and 24 h, to analyse activation of mitogen activated
      protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)-AKT. Specific
      inhibitors for ERK1/2 MAPK (PD98059), p38 MAPK (SB203580), JNK MAPK (SP600125),
      or PI3K (LY294002) were used to determine the involvement of individual kinases
      in agonist-induced P-UAEC proliferation. 2-OHE2 and 4-OHE2 stimulated biphasic
      phosphorylation of ERK1/2, slow p38 and JNK phosphorylation over time, and rapid
      monophasic AKT phosphorylation. Furthermore, ERK1/2, p38 and JNK MAPKs, but not
      PI3K, were individually necessary for catecholoestradiol-induced proliferation.
      In addition, when comparing the signalling mechanisms of the catecholoestradiols,
      to 17beta-oestradiol and catecholamines, we observed that convergent MAPKs
      signalling pathways facilitate P-UAEC proliferation induced by all of these
      hormones. Thus, all three members of the MAPK family mediate the mitogenic
      effects of catecholoestradiols in the endothelium during pregnancy. Furthermore,
      the convergent signalling of MAPKs involved in catecholoestradiol-, 17beta
      oestradiol- and catecholamine-induced endothelial cell proliferation may be
      indicative of unappreciated evolutionary functional redundancy to facilitate
      angiogenesis and ensure maintenance of uterine blood flow during pregnancy.

PMID- 28436999
TI  - Clinical practice guidelines on the evidence-based use of integrative therapies
      during and after breast cancer treatment.
AB  - Answer questions and earn CME/CNE Patients with breast cancer commonly use
      complementary and integrative therapies as supportive care during cancer
      treatment and to manage treatment-related side effects. However, evidence
      supporting the use of such therapies in the oncology setting is limited. This
      report provides updated clinical practice guidelines from the Society for
      Integrative Oncology on the use of integrative therapies for specific clinical
      indications during and after breast cancer treatment, including anxiety/stress,
      depression/mood disorders, fatigue, quality of life/physical functioning,
      chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced
      peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines
      are based on a systematic literature review from 1990 through 2015. Music
      therapy, meditation, stress management, and yoga are recommended for
      anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music
      therapy are recommended for depression/mood disorders. Meditation and yoga are
      recommended to improve quality of life. Acupressure and acupuncture are
      recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L
      carnitine is not recommended to prevent chemotherapy-induced peripheral
      neuropathy due to a possibility of harm. No strong evidence supports the use of
      ingested dietary supplements to manage breast cancer treatment-related side
      effects. In summary, there is a growing body of evidence supporting the use of
      integrative therapies, especially mind-body therapies, as effective supportive
      care strategies during breast cancer treatment. Many integrative practices,
      however, remain understudied, with insufficient evidence to be definitively
      recommended or avoided. CA Cancer J Clin 2017;67:194-232. (c) 2017 American
      Cancer Society.

PMID- 28437008
TI  - Effects from metal ion in tumor endothelial marker 8 and anthrax protective
      antigen: BioLayer Interferometry experiment and molecular dynamics simulation
      study.
AB  - One of the anthrax receptors, tumor endothelial marker 8 (TEM8), is reported to
      be a potential anticancer target due to its over-expression during tumor
      angiogenesis. To extend our BioLayer Interferometry study in PA-TEM8 binding, we
      present a computational approach to reveal the role of an integral metal ion on
      receptor structure and binding thermodynamics. We estimated the interaction
      energy between PA and TEM8 using computer simulation. Consistent with
      experimental study, computational results indicate the metal ion in TEM8
      contributes significantly to the binding affinity, and PA-TEM8 binding is more
      favorable in the presence of Mg2+ than Ca2+ . Further, computational analysis
      suggests that the differences in PA-TEM8 binding affinity are comparable to the
      closely related integrin proteins. The conformation change, which linked to
      changes in activity of integrins, was not found in TEM8. In the present of Mg2+ ,
      TEM8 remains in a conformation analogous to an integrin open (high-affinity)
      conformation. (c) 2017 Wiley Periodicals, Inc.

PMID- 28437009
TI  - Conformational changes of ubiquitin under high pressure conditions: A pressure
      simulated tempering molecular dynamics study.
AB  - Molecular dynamics simulations for the system of ubiquitin were performed with
      pressure simulated tempering to study pressure-induced conformational changes of
      ubiquitin. The pressure dependence of ubiquitin was analyzed in a wide range of
      pressure from atmospheric pressure (0.1 MPa) to 1.0 GPa. The fluctuation of the
      distance between amino-acid residues and the distribution of a largely
      fluctuating distance were calculated. The large fluctuation of the L8-E34
      distance induced by pressure means that the conformation of ubiquitin changes
      under high pressure conditions. There were more water molecules near the largely
      fluctuating region at high pressure than at low pressure. The pressure dependence
      of interaction energies among ubiquitin and water was also calculated to
      investigate the role of water for the pressure-induced conformational changes of
      ubiquitin. The protein-water interaction is important when the conformation of
      ubiquitin changes at high pressure. (c) 2017 Wiley Periodicals, Inc.

PMID- 28437010
TI  - Technical Note: Comparison of peripheral patient dose from MR-guided 60 Co
      therapy and 6 MV linear accelerator IGRT.
AB  - PURPOSE: The use of X-ray imaging in radiation therapy can give a substantial
      dose to the patient. A Cobalt machine combined with an magnetic resonance imaging
      (MRI) was recently introduced to clinical work. One positive aspect of using non
      ionizing imaging devices is the reduction of the patient exposure. The purpose of
      this study was to quantify the difference in out-of-field dose to the patient
      between the image guided radiation therapy (IGRT) treatment applied with a linear
      accelerator with cone beam CT (CBCT) equipment and a Cobalt machine combined with
      an MRI. METHODS: The treatment of a rhabdomyosarcoma in the prostate was planned
      and irradiated using different modalities and radiation therapy machines. The
      whole-body dose was measured for a 3D-conformal radiation therapy (3DCRT), an
      intensity-modulated radiation therapy (IMRT), and a volumetric-modulated arc
      therapy plan applied with a conventional linear accelerator operated at 6 MV beam
      energy. Additionally, the dose of an IMRT plan applied with a 60 Co machine
      combined with an MRI was measured. Furthermore, the dose of one CBCT scan using
      the linear accelerator's on-board imaging system was determined. The 3D dose
      measurements were performed in an anthropomorphic phantom containing 168 slots
      for thermoluminescence dosimeters (TLDs). A combination of LiF:Mg,Ti (TLD100) and
      LiF:Mg,Cu,P (TLD100H) was used to accurately determine the in- and out-of-field
      dose. The plans were rescaled to different fractionation schemes (2 Gy, 3 Gy, and
      5 Gy fraction dose) and the dose of one CBCT scan was additionally added to the
      treatment dose per fraction applied with the linear accelerator. The resulting
      absorbed doses per fraction of the two machines were compared. RESULTS: In the
      target region, all measured treatment plans presented the same magnitude of dose,
      while the CBCT dose was a factor of 100 smaller. Close to the planned target
      volume (PTV), the dose from the 60 Co machine was a factor of two higher compared
      with the 3DCRT + CBCT dose. Up to 45 cm from the PTV, the treatment applied with
      the 60 Co-sources showed an increased out-of-field dose compared to the linear
      accelerator + CBCT IGRT treatments. Further away from the PTV in the region where
      leakage from the gantry head is dominating, the out-of-field dose of the Cobalt
      machine was smaller compared to the linear accelerator + CBCT. CONCLUSION: The
      peripheral dose of the 60 Co machine combined with an MRI is larger up to 45 cm
      from the PTV and further away, it is lower than the dose from a linear
      accelerator + CBCT treatment. The presented fractionation schemes had a marginal
      impact on the results.

PMID- 28437011
TI  - Noise reduction and functional maps image quality improvement in dynamic CT
      perfusion using a new k-means clustering guided bilateral filter (KMGB).
AB  - PURPOSE: Dynamic CT perfusion (CTP) consists in repeated acquisitions of the same
      volume in different time steps, slightly before, during and slightly afterwards
      the injection of contrast media. Important functional information can be derived
      for each voxel, which reflect the local hemodynamic properties and hence the
      metabolism of the tissue. Different approaches are being investigated to exploit
      data redundancy and prior knowledge for noise reduction of such datasets, ranging
      from iterative reconstruction schemes to high dimensional filters. METHODS: We
      propose a new spatial bilateral filter which makes use of the k-means clustering
      algorithm and of an optimal calculated guiding image. We named the proposed
      filter as k-means clustering guided bilateral filter (KMGB). In this study, the
      KMGB filter is compared with the partial temporal non-local means filter (PATEN),
      with the time-intensity profile similarity (TIPS) filter, and with a new version
      derived from it, by introducing the guiding image (GB-TIPS). All the filters were
      tested on a digital in-house developed brain CTP phantom, were noise was added to
      simulate 80 kV and 200 mAs (default scanning parameters), 100 mAs and 30 mAs.
      Moreover, the filters performances were tested on 7 noisy clinical datasets with
      different pathologies in different body regions. The original contribution of our
      work is two-fold: first we propose an efficient algorithm to calculate a guiding
      image to improve the results of the TIPS filter, secondly we propose the
      introduction of the k-means clustering step and demonstrate how this can
      potentially replace the TIPS part of the filter obtaining better results at lower
      computational efforts. RESULTS: As expected, in the GB-TIPS, the introduction of
      the guiding image limits the over-smoothing of the TIPS filter, improving spatial
      resolution by more than 50%. Furthermore, replacing the time-intensity profile
      similarity calculation with a fuzzy k-means clustering strategy (KMGB) allows to
      control the edge preserving features of the filter, resulting in improved spatial
      resolution and CNR both for CT images and for functional maps. In the phantom
      study, the PATEN filter showed overall the poorest results, while the other
      filters showed comparable performances in terms of perfusion values preservation,
      with the KMGB filter having overall the best image quality. CONCLUSION: In
      conclusion, the KMGB filter leads to superior results for CT images and
      functional maps quality improvement, in significantly shorter computational times
      compared to the other filters. Our results suggest that the KMGB filter might be
      a more robust solution for halved-dose CTP datasets. For all the filters
      investigated, some artifacts start to appear on the BF maps if one sixth of the
      dose is simulated, suggesting that no one of the filters investigated in this
      study might be optimal for such a drastic dose reduction scenario.

PMID- 28437012
TI  - Leptin and NGF in saliva of patients with diabetes mellitus type 2: A pilot
      study.
AB  - AIMS: This study aimed to measure salivary levels of leptin and nerve growth
      factor (NGF) in patients with type 2 diabetes (T2D) and to compare with healthy
      subjects. In addition, markers previously evaluated in diabetes, including
      insulin, hepatocyte growth factor (HGF), and monocyte chemoattractant protein-1
      (MCP-1), and markers of inflammation interleukin ([IL]-1b, IL-6, IL-8, Tumor
      necrosis factor alpha [TNF-alpha]), were also measured in saliva to evaluate
      possible relationship of these markers with the new analytes evaluated in the
      study. METHODS: Unstimulated whole saliva was collected by passive drooling from
      a total of 65 individuals (34 controls and 31 with T2D) and used for leptin, NGF,
      HGF, MCP-1, insulin, IL-1b, IL-6, IL-8, and TNF-alpha determination. RESULTS:
      Salivary leptin was 2.1 higher in T2D than in healthy controls (P<.001), while no
      statistically significant differences were detected between the two groups in
      salivary concentrations of NGF. Salivary IL-6, TNF-alpha, insulin, and MCP-1 were
      higher in DM in comparison with controls (P<.05 in all cases). Leptin showed
      positive significant correlations with MCP-1, IL-6, TNF-alpha, and insulin, while
      NGF positively correlated with HGF, MCP-1, IL-1 beta, IL-6, and TNF-alpha.
      CONCLUSIONS: This pilot study indicates that salivary leptin is increased in
      patients with T2D being positively correlated with insulin and pro-inflammatory
      cytokines and should be further explored as a non-invasive biomarker of T2D. In
      addition, salivary NGF was positively correlated with pro-inflammatory cytokines
      and further studies should be performed to evaluate whether it could be useful to
      detect diabetic neuropathy in T2D patients.

PMID- 28437013
TI  - The prognostic value of B7-H6 protein expression in human oral squamous cell
      carcinoma.
AB  - OBJECTIVES: To investigate the expression and prognostic value of B7-H6 protein
      in oral squamous cell carcinoma tissues. MATERIALS AND METHODS: A total of 50
      oral squamous cell carcinoma samples, 10 oral leukoplakia (OLK) samples, and 17
      normal controls were included in the analysis. The expression of B7-H6 in oral
      squamous cell carcinoma, OLK, and normal controls was evaluated by
      immunohistochemical assay. RESULTS: The B7-H6 protein expression was
      significantly higher in oral squamous cell carcinoma tissues than that in normal
      oral mucosa. Furthermore, a significant relationship was found between the
      expression of B7-H6 and differentiation, but not with age, sex, tumor size, lymph
      metastasis, clinical stage, or recurrence. Further, the survival curves showed
      that B7-H6 was an independent prognostic factor of overall survival and disease
      free survival in oral squamous cell carcinoma. Moreover, multivariate survival
      analysis by COX proportional hazard regression model revealed that the
      recurrence, differentiation, and expression of B7-H6 were related to the
      prognosis. Lastly, we verified the prognostic value of B7-H6 in oral squamous
      cell carcinoma. CONCLUSIONS: B7-H6 may represent a new prognostic marker for oral
      squamous cell carcinoma.

PMID- 28437014
TI  - Cyclodextrin Films with Fast Solvent Transport and Shape-Selective Permeability.
AB  - This study describes the molecular-level design of a new type of filtration
      membrane made of crosslinked cyclodextrins-inexpensive macrocycles of glucose,
      shaped like hollow truncated cones. The channel-like cavities of cyclodextrins
      spawn numerous paths of defined aperture in the separation layer that can
      effectively discriminate between molecules. The transport of molecules through
      these membranes is highly shape-sensitive. In addition, the presence of
      hydrophobic (cavity) and hydrophilic (ester-crosslinked outer part) domains in
      these films results in high permeances for both polar and nonpolar solvents.

PMID- 28437015
TI  - One-Step Solution Phase Growth of Transition Metal Dichalcogenide Thin Films
      Directly on Solid Substrates.
AB  - Ultrathin transition metal dichalcogenides (TMDs) have exotic electronic
      properties. With success in easy synthesis of high quality TMD thin films, the
      potential applications will become more viable in electronics, optics, energy
      storage, and catalysis. Synthesis of TMD thin films has been mostly performed in
      vacuum or by thermolysis. So far, there is no solution phase synthesis to produce
      large-area thin films directly on target substrates. Here, this paper reports a
      one-step quick synthesis (within 45-90 s) of TMD thin films (MoS2 , WS2 , MoSe2 ,
      WSe2 , etc.) on solid substrates by using microwave irradiation on a precursor
      containing electrolyte solution. The numbers of the quintuple layers of the TMD
      thin films are precisely controllable by varying the precursor's concentration in
      the electrolyte solution. A photodetector made of MoS2 thin film comprising of
      small size grains shows near-IR absorption, supported by the first principle
      calculation, exhibits a high photoresponsivity (>300 mA W-1 ) and a fast response
      (124 us). This study paves a robust way for the synthesis of various TMD thin
      films in solution phases.

PMID- 28437016
TI  - Electromechanical Nanogenerator-Cell Interaction Modulates Cell Activity.
AB  - Noninvasive methods for in situ electrical stimulation of human cells open new
      frontiers to future bioelectronic therapies, where controlled electrical impulses
      could replace the use of chemical drugs for disease treatment. Here, this study
      demonstrates that the interaction of living cells with piezoelectric
      nanogenerators (NGs) induces a local electric field that self-stimulates and
      modulates their cell activity, without applying an additional chemical or
      physical external stimulation. When cells are cultured on top of the NGs, based
      on 2D ZnO nanosheets, the electromechanical NG-cell interactions stimulate the
      motility of macrophages and trigger the opening of ion channels present in the
      plasma membrane of osteoblast-like cells (Saos-2) inducing intracellular calcium
      transients. In addition, excellent cell viability, proliferation, and
      differentiation are validated. This in situ cell-scale electrical stimulation of
      osteoblast-like cells can be extrapolated to other excitable cells such as
      neurons or muscle cells, paving the way for future bioelectronic medicines based
      on cell-targeted electrical impulses.

PMID- 28437017
TI  - Determination of the enantiomeric purity of the selective dopamine transporter
      inhibitor (+)-R,R-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol.
AB  - (+)-R,R-D-84 ((+)-R,R-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol)
      is a promising pharmacological tool for the dopamine transporter (DAT), due to
      its high affinity and selectivity for this target. In this study, an analytical
      method to ascertain the enantiomeric purity of this compound was established. For
      this purpose, a high-performance liquid chromatographic (HPLC) method, based on a
      cellulose derived chiral stationary phase (CSP) was developed. The method was
      characterized concerning its specificity, linearity, and range. It was shown that
      the method is suitable to determine an enantiomeric excess of up to 99.8%. With
      only a few adjustments, this analytical CSP-HPLC method is also well suited to
      separate (+)-R,R-D-84 from its enantiomer in a semipreparative scale.

PMID- 28437018
TI  - Polar Side Chains Enhance Processability, Electrical Conductivity, and Thermal
      Stability of a Molecularly p-Doped Polythiophene.
AB  - Molecular doping of organic semiconductors is critical for optimizing a range of
      optoelectronic devices such as field-effect transistors, solar cells, and
      thermoelectric generators. However, many dopant:polymer pairs suffer from poor
      solubility in common organic solvents, which leads to a suboptimal solid-state
      nanostructure and hence low electrical conductivity. A further drawback is the
      poor thermal stability through sublimation of the dopant. The use of oligo
      ethylene glycol side chains is demonstrated to significantly improve the
      processability of the conjugated polymer p(g4 2T-T)-a polythiophene-in polar
      aprotic solvents, which facilitates coprocessing of dopant:polymer pairs from the
      same solution at room temperature. The use of common molecular dopants such as
      2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) and 2,3-dichloro
      5,6-dicyano-1,4-benzoquinone (DDQ) is explored. Doping of p(g4 2T-T) with F4TCNQ
      results in an electrical conductivity of up to 100 S cm-1 . Moreover, the
      increased compatibility of the polar dopant F4TCNQ with the oligo ethylene glycol
      functionalized polythiophene results in a high degree of thermal stability at up
      to 150  degrees C.

PMID- 28437019
TI  - Extending Unique 1D Borate Chains to 3D Frameworks by Introducing Metallic Nodes.
AB  - Two novel alkali/alkaline-earth borates, Ba6 [B6 O9 (OH)6 ]2 (H3 BO3 ) (1) and
      Li7 MAlB12 O24 (M=Ba, Sr, Ca) (2 a-c), with 1D and 3D structures have been made
      hydrothermally and characterized. 1 features a rare 1D anionic chain built by
      hexaborate clusters of B6 O11 (OH)6 ; each made of six BO4 /BO2 (OH)2 tetrahedra.
      The anionic chains are embedded in the channels of a Ba6 -based wheel-cluster
      open-framework. On the basis of the structural analyses of 1, by incorporating Al
      atoms as the linkers and tuning the reaction conditions, the novel anhydrous 3D
      aluminoborates (ABOs) 2 a-c have been successfully obtained, constructed from B6
      O14 -based cluster chains and AlO6 octahedra. The 3D ABO framework and 3D Ba-O-Li
      network are interpenetrated to give a final dense structure. The study not only
      realized the expansion of the structure from the 1D chain of 1 to the 3D dense
      ABOs 2 a-c, but also obtained the first 3D AlO6 -containing ABOs made under
      hydrothermal conditions. Different from the previously known 4-connected zeolite
      type ABOs, alternately arranged from AlO4 tetrahedra and oxo-boron clusters, the
      AlO6 octahedra in 2 a-c as the linkers join to six 1D B6 O14 -based cluster
      chains to produce 3D ABOs. The optical diffuse reflectance spectra reveal that 2
      a-c have wide range transparency. In addition, the thermal property analysis
      proves that 2 a-c are congruently melting compounds and possess high
      thermostability.

PMID- 28437020
TI  - Deactivation of a Cobalt Catalyst for Water Reduction through Valence
      Tautomerism.
AB  - The activity of the water reduction catalyst [CoIII (L1 )(pyr)2 ]PF6 (1), where
      (L1 )2- is a bis-amido pyridine ligand and pyr is pyrrolidine, is investigated.
      Catalyst 1 has an overpotential of 0.54 V and a high observed TOF of 23 min-1 ,
      albeit for a relatively short time. Considering the significant activity of 1 and
      aiming to improve catalyst design, a detailed structural and electronic study is
      performed to understand the mechanisms of deactivation. Experimental and
      theoretical evidence support that the metal-reduced [CoI (L1 )]- is in tautomeric
      equilibrium with the ligand-reduced [CoII (L1. )]- species. While [CoI (L1 )]-
      favors formation of a CoIII -H- relevant for catalysis, the [CoII (L1. )]-
      species leads to ligand protonation, structural distortions, and, ultimatley,
      catalyst deactivation.

PMID- 28437021
TI  - Optimum outcome achievement in partial nephrectomy for T1 renal masses: a
      contemporary analysis of open and robot-assisted cases.
AB  - OBJECTIVES: To compare optimum outcome achievement in open partial nephrectomy
      (OPN) with that in robot-assisted partial nephrectomy (RAPN). PATIENTS AND
      METHODS: Using our institutional partial nephrectomy (PN) database, we reviewed
      605 cases performed for unifocal clinical T1 renal masses in non-solitary kidneys
      between 2011 and 2015. Tetrafecta, which was defined as negative surgical
      margins, freedom from peri-operative complications, >=80% renal function
      preservation, and no chronic kidney disease upstaging, was chosen as the
      composite optimum outcome. Factors associated with tetrafecta achievement were
      assessed using multivariable logistic regression, with adjustment for age,
      gender, race, Charlson comorbidity score, body mass index, chronic kidney
      disease, tumour size, tumour complexity and approach. RESULTS: The overall
      tetrafecta achievement rate was 38%. Negative margins, freedom from
      complications, and optimum functional preservation were achieved in 97.1%, 73.6%
      and 54.2% of cases, respectively. For T1a masses, the tetrafecta achievement rate
      was similar between approaches (P = 0.97), but for T1b masses, the robot-assisted
      approach achieved significantly higher tetrafecta rates (43.0% vs 21.3%; P <
      0.01). On multivariable analysis, the robot-assisted approach had 2.6-fold higher
      odds of tetrafecta achievement than the open approach, primarily because of lower
      peri-operative morbidity, specifically related to wound complications. Positive
      surgical margin rates and renal function preservation were similar in the two
      approaches. CONCLUSIONS: Optimum outcomes are readily achieved regardless of PN
      approach. The robot-assisted approach may facilitate optimum outcome achievement
      for 4-7-cm masses by minimizing wound complications.

PMID- 28437022
TI  - "Wiring" Fe-Nx -Embedded Porous Carbon Framework onto 1D Nanotubes for Efficient
      Oxygen Reduction Reaction in Alkaline and Acidic Media.
AB  - This study presents a novel metal-organic-framework-engaged synthesis route based
      on porous tellurium nanotubes as a sacrificial template for hierarchically porous
      1D carbon nanotubes. Furthermore, an ultrathin Fe-ion-containing polydopamine
      layer has been introduced to generate highly effective FeNx C active sites into
      the carbon framework and to induce a high degree of graphitization. The
      synergistic effects between the hierarchically porous 1D carbon structure and the
      embedded FeNx C active sites in the carbon framework manifest in superior
      catalytic activity toward oxygen reduction reaction (ORR) compared to Pt/C
      catalyst in both alkaline and acidic media. A rechargeable zinc-air battery
      assembled in a decoupled configuration with the nonprecious pCNT@Fe@GL/CNF ORR
      electrode and Ni-Fe LDH/NiF oxygen evolution reaction (OER) electrode exhibits
      charge-discharge overpotentials similar to the counterparts of Pt/C ORR electrode
      and IrO2 OER electrode.

PMID- 28437023
TI  - Authors' overarching reply to all the responses received to the systematic
      literature review on shaken baby syndrome.

PMID- 28437024
TI  - Photon-Pair Generation with a 100 nm Thick Carbon Nanotube Film.
AB  - Nonlinear optics based on bulk materials is the current technique of choice for
      quantum-state generation and information processing. Scaling of nonlinear optical
      quantum devices is of significant interest to enable quantum devices with high
      performance. However, it is challenging to scale the nonlinear optical devices
      down to the nanoscale dimension due to relatively small nonlinear optical
      response of traditional bulk materials. Here, correlated photon pairs are
      generated in the nanometer scale using a nonlinear optical device for the first
      time. The approach uses spontaneous four-wave mixing in a carbon nanotube film
      with extremely large Kerr-nonlinearity (~100 000 times larger than that of the
      widely used silica), which is achieved through careful control of the tube
      diameter during the carbon nanotube growth. Photon pairs with a coincidence to
      accidental ratio of 18 at the telecom wavelength of 1.5 um are generated at room
      temperature in a ~100 nm thick carbon nanotube film device, i.e., 1000 times
      thinner than the smallest existing devices. These results are promising for
      future integrated nonlinear quantum devices (e.g., quantum emission and
      processing devices).

PMID- 28437025
TI  - Effectiveness of paracetamol versus ibuprofen administration in febrile children:
      A systematic literature review.
AB  - AIM: The use of antipyretics to manage the febrile child is becoming increasingly
      popular. Paracetamol and ibuprofen are the most commonly used interventions to
      manage fever in children; however, there have been no comparative analyses. The
      aim of the study is to evaluate the evidence comparing paracetamol to ibuprofen
      in the treatment of fever in children. METHODS: A systematic review of randomised
      controlled trials investigating the administration of oral paracetamol and
      ibuprofen to reduce fever in children. Children aged 1 month to 12 years with a
      temperature between 37.5 and 41 degrees C were included. A total of 3023 papers
      were identified. After removal of duplications, application of inclusion criteria
      and screening, eight papers were subjected to critical appraisal and included in
      this study. RESULTS: Six of the studies identified that ibuprofen was slightly,
      but not significantly, better at reducing fever in children than paracetamol.
      Dosage variances and route of temperature measurement ranged between studies,
      limiting the comparability of studies. While ibuprofen was reported to be
      marginally more effective at reducing fever and fever associated discomfort in
      children, there is insufficient data to conclude that ibuprofen is superior to
      paracetamol. CONCLUSION: There is little evidence supporting the superior
      efficacy of paracetamol or ibuprofen in the treatment of fever in children with
      indications that both drugs are equally effective.

PMID- 28437027
TI  - Reprogrammable Assembly of Molecular Motor on Solid Surfaces via Dynamic Bonds.
AB  - Controllable assembly of molecular motors on solid surfaces is a fundamental
      issue for providing them to perform physical tasks. However, it can hardly be
      achieved by most previous methods due to their inherent limitations. Here, a
      general strategy is designed for the reprogrammable assembly of molecular motors
      on solid surfaces based on dynamic bonds. In this method, molecular motors with
      disulfide bonds can be remotely, reversibly, and precisely attached to solid
      surfaces with disulfide bonds, regardless of their chemical composition and
      microstructure. More importantly, it not only allows encoding geometric
      information referring to a pattern of molecular motors, but also enables erasing
      and re-encoding of geometric information via hemolytic photocleavage and
      recombination of disulfide bonds. Thus, solid surfaces can be regarded as
      "computer hardware", where molecular motors can be reformatted and reprogramed as
      geometric information.

PMID- 28437026
TI  - Analyzing epidermal growth factor receptor mutation status changes in advanced
      non-small-cell lung cancer at different sampling time-points of blood within one
      day.
AB  - BACKGROUND: We investigated whether different sampling time-points within one day
      would influence epidermal growth factor receptor mutation (EGFRm) status in
      plasma and evaluated the clinical outcomes according to the quantity analysis of
      EGFRm in circulating tumor DNA (ctDNA) in non-small-cell lung cancer (NSCLC).
      METHODS: EGFR-tyrosine kinase inhibitor naive advanced NSCLC patients who carried
      EGFRm in both tissues and ctDNA were enrolled in this study. Plasma samples were
      collected at three time-points within one day (at 8 am, 11 am and 2 pm) for EGFRm
      analysis by droplet digital PCR. RESULTS: Twenty-two advanced NSCLC patients were
      enrolled in the study. In a total of 66 blood specimens, the median EGFRm
      frequency was 7.13% (range 0-35.09%), and among them six specimens had less than
      1.0% EGFRm frequency. Moreover, one time-point blood specimen did not display any
      EGFRm, even by droplet digital PCR. The frequency of EGFRm changed dynamically
      across different time-points within one day, but the differences were not
      significant (P = 0.557). We observed that patients with a relatively high
      frequency of EGFRm (>6.76%) had a better response to gefitinib (P = 0.024).
      CONCLUSION: The release of ctDNA maybe a temporal heterogenous process. The
      different sampling time-points within one day did not seem to influence EGFRm
      status in ctDNA. The relative EGFRm frequency in ctDNA could predict a benefit of
      EGFR-tyrosine kinase inhibitor treatment for advanced NSCLC patients.

PMID- 28437028
TI  - European Section of Urotechnology educational video on fluoroscopic-guided
      puncture in percutaneous nephrolithotomy: all techniques step by step.
AB  - OBJECTIVE: To describe the most common fluoroscopic-guided access techniques
      during percutaneous nephrolithotomy (PCNL) in a step-by-step manner and to assist
      in the standardisation of their technique and terminology. METHODS: A high
      quality animation video was created for each of the respective fluoroscopic
      techniques, focusing into the parallel projection of external surgical manoeuvres
      and their effect in the three-dimensional space of the kidney. RESULTS: Four
      predominant fluoroscopic-guided percutaneous access techniques are available,
      each with different advantages and limitations. Monoplanar access is used when a
      stable single-axis fluoroscopic generator is available and is mostly based on
      surgeons' experience. Biplanar access uses a second fluoroscopy axis to assess
      puncture depth. The 'bull's eye' technique follows a coaxial to fluoroscopy
      puncture path and is associated with a shorter learning curve at the cost of
      increased hand radiation exposure. Hybrid and conventional triangulate techniques
      use target projection by two fluoroscopic planes to define the exact localisation
      of the target in space and access it through a third puncture site. CONCLUSIONS:
      Fluoroscopic guidance during PCNL puncture is a very efficient method for access
      establishment. The percutaneous surgeon should be familiar with all available
      variations of fluoroscopic approach in order to be prepared to adapt puncture
      technique for any given scenario.

PMID- 28437030
TI  - Selective Nucleation of GaAs on Si Nanofacets.
AB  - The early growth stage of GaAs by metal organic vapor phase epitaxy on a novel
      kind of Si substrate is investigated. The substrate consists of nanotips (NTs)
      fabricated on a Si(001) wafer by means of lithography and reactive ion etching.
      3D GaAs nanocrystals are found to nucleate with a probability of 90% on the
      (n0m), (-n0m), (0nm), and (0-nm) facets (n, m integers) of these NTs.
      Additionally, in terms of nucleation yield, an average of 2 GaAs nanocrystals in
      each of those facets is observed. By contrast, facets of type {+/-nnm} remain
      virtually free of any 3D nuclei. A simple model based on the kinetics of the
      growth is used to explain the facet selective 3D nucleation. The model is
      consistent with a similar selectivity observed on micrometer-sized substrate
      features.

PMID- 28437029
TI  - Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment
      feasibility and baseline demographics of a randomized trial of diet in men on
      active surveillance for prostate cancer.
AB  - OBJECTIVE: To assess the feasibility of performing national, randomized trials of
      dietary interventions for localized prostate cancer. METHODS: The Men's Eating
      and Living (MEAL) study (CALGB 70807 [Alliance]) is a phase III clinical trial
      testing the efficacy of a high-vegetable diet to prevent progression in patients
      with prostate cancer on active surveillance (AS). Participants were randomized to
      a validated diet counselling intervention or to a control condition. Chi-squared
      and Kruskal-Wallis analyses were used to assess between-group differences at
      baseline. RESULTS: Between 2011 and 2015, 478 (103%) of a targeted 464 patients
      were randomized at 91 study sites. At baseline, the mean (sd) age was 64 (6)
      years and mean (sd) PSA concentration was 4.9 (2.1) ng/mL. Fifty-six (12%)
      participants were African-American, 17 (4%) were Hispanic/Latino, and 16 (3%)
      were Asian-American. There were no significant between-group differences for age
      (P = 0.98), race/ethnicity (P = 0.52), geographic region (P = 0.60), time since
      prostate cancer diagnosis (P = 0.85), PSA concentration (P = 0.96), clinical
      stage (T1c or T2a; P = 0.27), or Gleason sum (Gleason 6 or 3+4 = 7; P = 0.76). In
      a pre-planned analysis, the baseline prostate biopsy samples of the first 50
      participants underwent central pathology review to confirm eligibility, with an
      expectation that <10% would become ineligible. One of 50 participants (2%) became
      ineligible. CONCLUSION: The MEAL study shows the feasibility of implementing
      national, multi-institutional phase III clinical trials of diet for prostate
      cancer and of testing interventions to prevent disease progression in AS.

PMID- 28437032
TI  - Autonomic Receptor-mediated Regulation of Production and Release of Nitric Oxide
      in Normal and Malignant Human Urothelial Cells.
AB  - In the urinary bladder, the main source of NO seems to be the urothelium and the
      underlying suburothelium. In this study, we aimed to characterize how receptors
      in the human urothelium regulate the production and release of NO. For this, we
      cultured two human urothelial cell lines - the normal immortalized cell line
      UROtsa and the malignant cell line T24. These were treated with an array of
      agonists and antagonists with affinity for adrenergic, muscarinic and purinergic
      receptors. The production of NO and expression of nitric oxide synthase (NOS) was
      studied by immunocytochemistry and Western blotting. The amount of released NO
      was measured indirectly by detecting nitrite using amperometry and a Griess
      reaction kit. The results showed that NO, endothelial NOS and inducible NOS were
      predominantly produced and expressed in the close vicinity of the nucleus in
      untreated human urothelial cells. Upon treatment with a beta-adrenoceptor
      agonist, but not any of the other agonists or antagonists, the pattern of NO
      production changed, showing a more even production throughout the cytosol. The
      pattern of expression of endothelial NOS changed in a similar way upon dobutamine
      treatment. The release of nitrite, as a measurement of NO, increased after
      treatment with dobutamine from 0.31 +/- 0.029 to 1.97 +/- 0.18 nmol and 0.80 +/-
      0.12 to 3.27 +/- 0.24 nmol in UROtsa and T24, respectively. In conclusion, our
      results show that the expression of NOS and production of NO as well as the
      release of NO from human urothelial cells is regulated by beta-adrenoceptor
      activation.

PMID- 28437031
TI  - Patient-reported outcome (PRO) questionnaires for men who have radical surgery
      for prostate cancer: a conceptual review of existing instruments.
AB  - To critically review conceptual frameworks for available patient-reported outcome
      (PRO) questionnaires in men having radical prostatectomy (RP), psychometrically
      evaluate each questionnaire, and identify whether each is appropriate for use at
      the level of the individual patient. We searched PubMed, the Reports and
      Publications database of the University of Oxford Patient-Reported Outcomes
      Measurement Group and the website of the International Consortium for Health
      Outcomes Measurement (ICHOM) for psychometric reviews of prostate cancer-specific
      PRO questionnaires. From these we identified relevant questionnaires and
      critically appraised the conceptual content, guided by the Wilson and Cleary
      framework and psychometric properties, using well established criteria. The
      searches found four reviews and one recommendation paper. We identified seven
      prostate cancer-specific PROs: the Expanded Prostate Cancer Index Composite-26
      (EPIC-26), Expanded Prostate Cancer Index Composite-50 (EPIC-50), University of
      California-Los Angeles Prostate Cancer Index (UCLA-PCI), Functional Assessment of
      Cancer Therapy - Prostate Cancer Subscale (FACT-P PCS), European Organisation for
      Research and Treatment of Cancer Quality of Life Questionnaire - prostate
      specific 25-item (EORTC QLQ-PR25), Prostate Cancer - Quality of Life (PC-QoL),
      and Symptom Tracking and Reporting (STAR). Six out of seven measures purported to
      measure health-related quality of life (HRQL), but items focused strongly on
      urinary and sexual symptoms/functioning. The remaining questionnaire (STAR)
      claimed to assess functional recovery after RP. The psychometric evidence for
      these questionnaires was incomplete and variable in quality; none had evidence
      that they were appropriate for use with individual patients. Several
      questionnaires provide the basis of measures of urinary and/or sexual
      symptoms/functioning. Further work should explore other aspects of HRQL that are
      important for men having RP. Further psychometric work is also needed to
      determine whether they can be used at the individual level.

PMID- 28437033
TI  - Electrical Stress Influences the Efficiency of CH3 NH3 PbI3 Perovskite Light
      Emitting Devices.
AB  - Organic-inorganic hybrid perovskite materials are emerging as semiconductors with
      potential application in optoelectronic devices. In particular, perovskites are
      very promising for light-emitting devices (LEDs) due to their high color purity,
      low nonradiative recombination rates, and tunable bandgap. Here, using pure CH3
      NH3 PbI3 perovskite LEDs with an external quantum efficiency (EQE) of 5.9% as a
      platform, it is shown that electrical stress can influence device performance
      significantly, increasing the EQE from an initial 5.9% to as high as 7.4%.
      Consistent with the enhanced device performance, both the steady-state
      photoluminescence (PL) intensity and the time-resolved PL decay lifetime increase
      after electrical stress, indicating a reduction in nonradiative recombination in
      the perovskite film. By investigating the temperature-dependent characteristics
      of the perovskite LEDs and the cross-sectional elemental depth profile, it is
      proposed that trap reduction and resulting device-performance enhancement is due
      to local ionic motion of excess ions, likely excess mobile iodide, in the
      perovskite film that fills vacancies and reduces interstitial defects. On the
      other hand, it is found that overstressed LEDs show irreversibly degraded device
      performance, possibly because ions initially on the perovskite lattice are
      displaced during extended electrical stress and create defects such as vacancies.

PMID- 28437034
TI  - Robot-assisted vs open radical prostatectomy: the day after.

PMID- 28437036
TI  - From bed to bench: 7th Joint meeting of European Tissue Repair Society (ETRS)
      with the Wound Healing Society (WHS) and the 25th Annual Meeting of ETRS in
      Copenhagen, Denmark.

PMID- 28437035
TI  - The association between oral examination findings and computed tomographic
      appearance of the equine temporomandibular joint.
AB  - BACKGROUND: The temporomandibular joint (TMJ) forms the junction between the
      maxilla and mandible. Movement of the jaw and resulting masticatory forces have
      been extensively studied in the horse; however, less is known about the inter
      relationship between this joint and oral and dental pathology. OBJECTIVES: To
      determine the association between specific oral and dental pathologies and
      anatomical variations of the TMJ imaged with computed tomography (CT) in horses
      with asymptomatic TMJs. STUDY DESIGN: Retrospective cross-sectional study.
      METHODS: Horses (n = 201) from three practices with a complete oral examination
      and skull or upper cervical CT study were reviewed. Age, breed, sex, clinical
      presentation, oral examination findings, slice width and practice were recorded.
      Alterations in contour and density of the mandibular condyle, mandibular fossa
      and intra-articular disc were also documented. Logistic regression, corrected for
      clustering by practice, was used to determine whether CT anatomical variations
      were significantly associated with the oral examination findings. RESULTS: Horses
      categorised as having abnormal TMJs were older than those with normal TMJ. Horses
      with periodontal disease were less likely to have abnormal TMJ findings compared
      with horses with no oral pathology. In contrast, horses with infundibular disease
      were more likely to have TMJ abnormalities. MAIN LIMITATIONS: Due to the cross
      sectional nature of the study, it was difficult to establish whether oral
      pathology preceded TMJ abnormalities. CONCLUSIONS: Despite examining over 200
      horses of varying ages, the biological significance of the observed associations
      between oral, or dental disease and anatomically appreciable temporomandibular
      joint disorders remains uncertain.

PMID- 28437038
TI  - Impact of preoperative risk on metastatic progression and cancer-specific
      mortality in patients with adverse pathology at radical prostatectomy.
AB  - OBJECTIVE: To evaluate the impact of preoperative risk category on metastatic
      disease and prostate cancer-specific mortality (CSM) in patients with prostate
      cancer (PCa) with adverse pathology at radical prostatectomy (RP). PATIENTS AND
      METHODS: The records of 6 943 patients who underwent RP at a European tertiary
      centre were analysed. Biochemical recurrence (BCR), metastatic disease and CSM
      were assessed for patients with adverse pathology at RP, and stratified according
      to preoperative low- vs intermediate-/high-risk PCa groups. Kaplan-Meier,
      cumulative incidence, Cox regression and competing risk regression analyses were
      performed. RESULTS: In patients with extracapsular extension, the metastatic
      disease rate was 1.6% vs 8% (P < 0.001) and the CSM rate was 2% vs 5% (P = 0.041)
      for low vs intermediate-/high-risk patients, respectively, at 10 years. In
      patients with pathological Gleason score >=3+4, the metastatic disease rate was
      3.0% vs 12% (P < 0.001) and the CSM rate was 3% vs 8%, respectively (P < 0.001).
      In patients with positive surgical margins (PSMs), the metastatic disease rate
      was 2.9% vs 15% (P < 0.001) and the CSM rate was 4% vs 10%, respectively (P =
      0.0001). Low-risk status was a predictive factor for metastatic disease in
      patients with pathological Gleason score >=3+4 (hazard ratio [HR] 0.51),
      pathological Gleason score >=4+3 (HR 0.41) and PSMs (HR 0.46) and was a
      predictive factor for CSM risk in patients with pathological Gleason score >=3+4
      (HR 0.62). CONCLUSIONS: Patients with low-risk PCa were at significantly lower
      risk of metastatic disease and CSM than their intermediate-/high-risk
      counterparts, when adverse pathological features were identified at RP. This
      should be emphasized in the decision-making process after RP.

PMID- 28437037
TI  - Use of fondaparinux for thromboprophylaxis in an unfractionated heparin
      intolerant pregnant woman with thrombotic predisposition.
AB  - A 34-year-old primigravida who had undergone thrombectomy for deep venous
      thrombosis (DVT) in her leg and exhibited low protein S activity, indicating
      predisposition to thrombosis, developed DVT of the leg. No pulmonary embolism was
      detected. After anticoagulant therapy with unfractionated heparin was
      discontinued because of liver dysfunction, danaparoid treatment was administered
      in hospital. The patient had a normal delivery after 39 weeks' gestation with no
      recurrence of thrombosis. During her second pregnancy four years later, she gave
      herself fondaparinux injections. She delivered normally after 38 weeks' gestation
      without experiencing DVT. Fondaparinux may be a useful anticoagulant for heparin
      intolerant pregnant women.

PMID- 28437039
TI  - Uterine artery pseudoaneurysm bleeding one decade after caesarean section: A case
      report.
AB  - Uterine artery pseudoaneurysm (UAP) can cause severe secondary post-partum
      hemorrhage. The lag time between the triggering event and the manifestation of
      UAP reportedly usually occurs within a couple of weeks. In this case report, a 46
      year-old woman with no significant comorbidities presented with a one-month
      history of increasing lower abdominal pain. She had previously undergone two
      cesarean sections (14 and 10 years earlier). A computed tomography angiogram
      revealed a left UAP. The patient was successfully treated by selective
      embolization and had an uneventful recovery. In our case, the time period between
      the cesarean section and presentation was approximately 10 years with no other
      potential causative factors. This case highlights that UAP should be included as
      a differential diagnosis in all female patients presenting with pelvic pain and
      pelvic bleeding. More specifically, UAP should be considered after a previous
      history of cesarean section, as a delayed diagnosis can result in serious
      morbidity and even mortality.

PMID- 28437040
TI  - Care planning and coordination: Imperfect solutions in a complex world.

PMID- 28437041
TI  - Dental Implant Provisionalization Options.

PMID- 28437042
TI  - Using an Integrated Digital Approach to Treatment Planning.

PMID- 28437044
TI  - Challenges Faced by Foreign National Dentists.

PMID- 28437043
TI  - The Changing Face of Restorative Dentistry.

PMID- 28437045
TI  - FOCUS ON: Dental Photography.

PMID- 28437048
TI  - Provisionalization for Implant Dentistry.

PMID- 28437046
TI  - Somebody's Watching Me.

PMID- 28437049
TI  - Composite Versus Porcelain, Part 3: Modern Management of Deep Caries.

PMID- 28437050
TI  - Predictable Class II Restorations Using Sectional Matrices.

PMID- 28437051
TI  - The "Reservoir Restorative" Revolution.

PMID- 28437052
TI  - The Use of 3-D Imaging is Changing: Endodontic Diagnoses and Treatments.

PMID- 28437053
TI  - Long-Span Fixed Partial Denture Repair: A Conservative Modern Material Solution.

PMID- 28437054
TI  - Tonsillar Squamous Cell Carcinoma: An Additional Consideration for Atypical
      Glossodynia.

PMID- 28437055
TI  - Psychotic and Bipolar Disorders: Foreword.

PMID- 28437056
TI  - Psychotic and Bipolar Disorders: Schizophrenia.
AB  - Schizophrenia is the most common psychotic illness, typically appearing between
      the late teenage years and the mid-30s. The first episode of psychosis may be
      preceded by a prodromal period. Schizophrenia symptoms fall into six common
      symptom clusters: delusions and hallucinations, disorganization of speech,
      cognitive dysfunction, negative symptoms, affective symptoms, and motor system
      abnormalities. The diagnosis is based on criteria in the Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition, including exclusion of
      other possible medical or psychiatric etiologies of psychosis. The main goals
      during the initial evaluation of a patient with suspected schizophrenia are to
      rule out secondary etiologies of symptoms and to assess for significant comorbid
      conditions, balancing broad screening tests with the exclusion of specific
      disorders suggested by the presentation and history. After the initial
      evaluation, antipsychotic drug treatment should be initiated and consideration
      given to psychosocial treatments in conjunction with pharmacotherapy.
      Comanagement of the patient by a mental health subspecialist and a family
      physician is important to ensure appropriate screening, diagnosis, and management
      of common associated conditions.

PMID- 28437057
TI  - Psychotic and Bipolar Disorders: Behavioral Disorders in Dementia.
AB  - Psychosis is one of the most common conditions in later life, with dementia being
      a main contributing factor. The Diagnostic and Statistical Manual of Mental
      Disorders, Fifth Edition (DSM-5), now categorizes the various types of dementia
      as neurocognitive disorders. Alzheimer disease is a common cause of dementia and
      psychosis. Psychosis also is seen in patients with vascular dementia and dementia
      with Lewy bodies. Psychosis can be primary, caused by a psychiatric disorder
      listed in the DSM-5, or secondary, due to a medical or neurologic condition.
      Approximately 60% of psychosis cases are secondary. Accurate diagnosis is
      important to rule out serious medical conditions or reversible etiologies. A
      careful history should be obtained and a thorough physical examination performed.
      Several risk factors make older adults prone to psychosis: sensory deficits,
      social isolation, and cognitive decline, along with other etiologies. Multiple
      potential risks and adverse effects are associated with drugs used to manage
      psychosis in elderly patients. Therefore, various guidelines recommend
      nonpharmacologic interventions as first-line treatment. When moderate or severe
      psychotic symptoms remain, drugs can be initiated as second-line treatment.
      Antipsychotic drugs have been shown to be effective in managing psychosis
      associated with dementia.

PMID- 28437058
TI  - Psychotic and Bipolar Disorders: Antipsychotic Drugs.
AB  - Antipsychotic drugs block dopamine receptors and are used to manage psychosis as
      well as other mental illnesses that may or may not have psychotic features, such
      as bipolar disorders and major depressive disorder. First-generation
      antipsychotic drugs are more likely to cause adverse effects such as
      extrapyramidal symptoms and tardive dyskinesia. Adverse effects of second
      generation antipsychotic drugs typically are related to metabolic abnormalities
      such as weight gain, abnormal blood glucose levels, and elevated lipid levels.
      Neuroleptic malignant syndrome is a rare but serious adverse effect of
      antipsychotic drugs that causes mental status changes, hyperthermia, and
      generalized rigidity. Timely diagnosis is essential due to a high risk of related
      morbidities if the syndrome remains untreated. Some adverse effects of
      antipsychotics can be identified and managed so that patients can continue
      beneficial therapy while minimizing the physiologic consequences. Patients taking
      antipsychotic drugs should be monitored regularly for adverse effects.
      Antipsychotics are also associated with potential drug interactions, the most
      lethal being prolongation of the QT interval, which can lead to fatal
      arrhythmias. Antipsychotic drugs can be used in special populations, such as
      pregnant women, children, and elderly patients, per recommendation from a mental
      health subspecialist.

PMID- 28437059
TI  - Psychotic and Bipolar Disorders: Bipolar Disorder.
AB  - Bipolar disorder is a severe chronic mental illness that affects a large number
      of individuals. This disorder is separated into two major types, bipolar I
      disorder, with mania and typically recurrent depression, and bipolar II disorder,
      with recurrent major depression and hypomania. Patients with bipolar disorder
      spend the majority of time experiencing depression, and this typically is the
      presenting symptom. Because outcomes are improved with earlier diagnosis and
      treatment, physicians should maintain a high index of suspicion for bipolar
      disorder. The most effective long-term treatments are lithium and valproic acid,
      although other drugs also are used. In addition to referral to a mental health
      subspecialist for initiation and management of drug treatment, patients with
      bipolar disorder should be provided with resources for psychotherapy. Several
      comorbidities commonly associated with bipolar disorder include other mental
      disorders, substance use disorders, migraine headaches, chronic pain, stroke,
      metabolic syndrome, and cardiovascular disease. Family physicians who care for
      patients with bipolar disorder should focus their efforts on prevention and
      management of comorbidities. These patients should be assessed continually for
      risk of suicide because they are at high risk and their suicide attempts tend to
      be successful.

PMID- 28437061
TI  - Nano/micro-hierarchical-structured LiMn0.85Fe0.15PO4 cathode material for
      advanced lithium ion battery.
AB  - Nano/micro-hierarchical-structured LiMn0.85Fe0.15PO4/C cathode materials were
      prepared by solvothermal synthesis combined with spray pyrolysis. XRD patterns
      and HRTEM images indicate that the LiMn0.85Fe0.15PO4/C are well crystallized and
      no impurity is observed. The as-prepared LiMn0.85Fe0.15PO4/C porous spherical
      (0.5-11 ?m) are accumulated by primary nanoparticles (~50 nm in width, 50-250 ?m
      in length). Adopting the sucrose as a carbon source, the cathode delivers a
      reversible discharge capacity of 171.2 mAh g-1 at 0.1C, almost exactly its
      theoretical capacity (~170 mAh g-1). Moreover, the composite exhibits high cycle
      stability without apparent capacity fading after 100 cycles at rates of 0.1C and
      1C. The outstanding electrochemical performances are partially due to Fe2+
      substituting and carbon coating which improve the electrical conductivity, and
      importantly due to its nano/micro-hierarchical structure, where primary
      nanoparticles exhibit high electrochemical activity, abundant mesopores benefit
      electrolyte penetration and hierarchical structure ensure the cycling stability.

PMID- 28437060
TI  - High Throughput and Quantitative Measurement of Microbial Metabolome by Gas
      Chromatography/Mass Spectrometry Using Automated Alkyl Chloroformate
      Derivatization.
AB  - The ability to identify and quantify small molecule metabolites derived from gut
      microbial-mammalian cometabolism is essential for the understanding of the
      distinct metabolic functions of the microbiome. To date, analytical protocols
      that quantitatively measure a complete panel of microbial metabolites in
      biological samples have not been established but are urgently needed by the
      microbiome research community. Here, we report an automated high-throughput
      quantitative method using a gas chromatography/time-of-flight mass spectrometry
      (GC/TOFMS) platform to simultaneously measure over one hundred microbial
      metabolites in human serum, urine, feces, and Escherichia coli cell samples
      within 15 min per sample. A reference library was developed consisting of 145
      methyl and ethyl chloroformate (MCF and ECF) derivatized compounds with their
      mass spectral and retention index information for metabolite identification.
      These compounds encompass different chemical classes including fatty acids, amino
      acids, carboxylic acids, hydroxylic acids, and phenolic acids as well as benzoyl
      and phenyl derivatives, indoles, etc., that are involved in a number of important
      metabolic pathways. Within an optimized range of concentrations and sample
      volumes, most derivatives of both reference standards and endogenous metabolites
      in biological samples exhibited satisfactory linearity (R2 > 0.99), good
      intrabatch reproducibility, and acceptable stability within 6 days (RSD < 20%).
      This method was further validated by examination of the analytical variability of
      76 paired human serum, urine, and fecal samples as well as quality control
      samples. Our method involved using high-throughput sample preparation,
      measurement with automated derivatization, and rapid GC/TOFMS analysis. Both
      techniques are well suited for microbiome metabolomics studies.

PMID- 28437062
TI  - Molecular Arrangement and Charge Transfer in C60/Graphene Heterostructures.
AB  - Charge transfer at the interface between dissimilar materials is at the heart of
      electronics and photovoltaics. Here we study the molecular orientation,
      electronic structure, and local charge transfer at the interface region of C60
      deposited on graphene, with and without supporting substrates such as hexagonal
      boron nitride. We employ ab initio density functional theory with van der Waals
      interactions and experimentally characterize interface devices using high
      resolution transmission electron microscopy and electronic transport. Charge
      transfer between C60 and the graphene is found to be sensitive to the nature of
      the underlying supporting substrate and to the crystallinity and local
      orientation of the C60. Even at room temperature, C60 molecules interfaced to
      graphene are orientationally locked into position. High electron and hole
      mobilities are preserved in graphene with crystalline C60 overlayers, which has
      ramifications for organic high-mobility field-effect devices.

PMID- 28437063
TI  - Charge Transport in Intermixed Regions of All-Polymer Solar Cells Studied by
      Conductive Atomic Force Microscopy.
AB  - Charge transport in intermixed regions of all-polymer solar cells based on a
      blend of poly(3-hexylthiophene) (P3HT; electron donor) with poly[2,7-(9,9
      didodecylfluorene)-alt-5,5-(4',7'-bis(2-thienyl)-2',1',3'-benzothiadiazole)]
      (PF12TBT; electron acceptor) was studied by conductive atomic force microscopy (C
      AFM). For a blend film fabricated from a chlorobenzene solution, intermixed
      regions were detected between the P3HT-rich and PF12TBT-rich domains. The overall
      hole current in the intermixed regions remained almost constant, both before and
      after thermal annealing at 80  degrees C, but it increased in the P3HT-rich
      domains. For a blend film fabricated from a chloroform solution, the entire
      observed area constituted an intermixed region, both before and after thermal
      annealing. The overall hole current in this film was significantly improved
      following thermal annealing at 120  degrees C. These finely mixed structures with
      efficient charge transport yielded a maximum power conversion efficiency of 3.5%.
      The local charge-transport properties in the intermixed region, as observed via C
      AFM, was found to be closely related to the photovoltaic properties, rather than
      the bulk-averaged properties or topological features.

PMID- 28437064
TI  - Rapid and Highly Sensitive Detection of Dopamine Using Conjugated Oxaborole-Based
      Polymer and Glycopolymer Systems.
AB  - A conjugated polymer interface consisting of an oxaborole containing polymer and
      a glycopolymer was used for achieving very high selectivity in dopamine (DA)
      detection. The optimum binding affinity between the polymers promotes the
      selectivity to DA through a displacement mechanism while remaining unaffected by
      other structurally related analogs and saccharide derivatives. Real-time
      detection of DA with very high selectivity and sensitivity has been demonstrated
      by immobilizing the polymer conjugates on surface plasmon resonance (SPR) and
      microcantilever (MCL) sensor platforms. Using the conjugated polymer sensing
      layer, the SPR biosensor was capable of detecting DA in the concentration range
      of 1 * 10-9 to 1 * 10-4 mol L-1, whereas the MCL sensor showed a limit of
      detection (LOD) of 5 * 10-11 mol L-1. We find that the sensing mechanism is based
      on DA-induced reversible swelling of the conjugated polymer layer and this allows
      regeneration and reuse of the sensor multiple times. Also, we conclude that SPR
      is a suitable sensor platform for DA in-line detection at clinical level
      considering the detection time and stability, whereas MCL can achieve a much
      lower LOD.

PMID- 28437066
TI  - Electric-Field-Driven Direct Desulfurization.
AB  - The ability to elucidate the elementary steps of a chemical reaction at the
      atomic scale is important for the detailed understanding of the processes
      involved, which is key to uncover avenues for improved reaction paths. Here, we
      track the chemical pathway of an irreversible direct desulfurization reaction of
      tetracenothiophene adsorbed on the Cu(111) closed-packed surface at the
      submolecular level. Using the precise control of the tip position in a scanning
      tunneling microscope and the electric field applied across the tunnel junction,
      the two carbon-sulfur bonds of a thiophene unit are successively cleaved.
      Comparison of spatially mapped molecular states close to the Fermi level of the
      metallic substrate acquired at each reaction step with density functional theory
      calculations reveals the two elementary steps of this reaction mechanism. The
      first reaction step is activated by an electric field larger than 2 V nm-1,
      practically in absence of tunneling electrons, opening the thiophene ring and
      leading to a transient intermediate. Subsequently, at the same threshold electric
      field and with simultaneous injection of electrons into the molecule, the
      exergonic detachment of the sulfur atom is triggered. Thus, a stable molecule
      with a bifurcated end is obtained, which is covalently bound to the metallic
      surface. The sulfur atom is expelled from the vicinity of the molecule.

PMID- 28437065
TI  - A Macrocyclic Peptide Ligand Binds the Oncogenic MicroRNA-21 Precursor and
      Suppresses Dicer Processing.
AB  - MicroRNAs (miRNAs) help orchestrate cellular growth and survival through post
      transcriptional mechanisms. The dysregulation of miRNA biogenesis can lead to
      cellular growth defects and chemotherapeutic resistance and plays a direct role
      in the development of many chronic diseases. Among these RNAs, miR-21 is
      consistently overexpressed in most human cancers, leading to the down-regulation
      of key tumor-suppressing and pro-apoptotic factors, suggesting that inhibition of
      miR-21 biogenesis could reverse these negative effects. However, targeted
      inhibition of miR-21 using small molecules has had limited success. To overcome
      difficulties in targeting RNA secondary structure with small molecules, we
      developed a class of cyclic beta-hairpin peptidomimetics which bind to RNA stem
      loop structures, such as miRNA precursors, with potent affinity and specificity.
      We screened an existing cyclic peptide library and discovered a lead structure
      which binds to pre-miR21 with KD = 200 nM and prefers it over other pre-miRNAs.
      The NMR structure of the complex shows that the peptide recognizes the Dicer
      cleavage site and alters processing of the precursor to the mature miRNA in vitro
      and in cultured cells. The structure provides a rationale for the peptide binding
      activity and clear guidance for further improvements in affinity and targeting.

PMID- 28437067
TI  - In Situ Synthesis of Tungsten-Doped SnO2 and Graphene Nanocomposites for High
      Performance Anode Materials of Lithium-Ion Batteries.
AB  - The composite of tungsten-doped SnO2 and reduced graphene oxide was synthesized
      through a simple one-pot hydrothermal method. According to the structural
      characterization of the composite, tungsten ions were doped in the unit cells of
      tin dioxide rather than simply attaching to the surface. Tungsten-doped SnO2 was
      in situ grown on the surface of graphene sheet to form a three-dimensional
      conductive network that enhanced the electron transportation and lithium-ion
      diffusion effectively. The issues of SnO2 agglomeration and volume expansion
      could be also avoided because the tungsten-doped SnO2 nanoparticles were
      homogeneously distributed on a graphene sheet. As a result, the nanocomposite
      electrodes of tungsten-doped SnO2 and reduced graphene oxide exhibited an
      excellent long-term cycling performance. The residual capacity was still as high
      as 1100 mA h g-1 at 0.1 A g-1 after 100 cycles. It still remained at 776 mA h g-1
      after 2000 cycles at the current density of 1A g-1.

PMID- 28437068
TI  - Observing the Overgrowth of a Second Metal on Silver Cubic Seeds in Solution by
      Surface-Enhanced Raman Scattering.
AB  - We report the development of an isocyanide-based molecular probe for in situ
      characterizing the overgrowth of a second metal on silver nanocrystal seeds in
      solution by surface-enhanced Raman scattering (SERS). As the first demonstration,
      we elucidate that the vibrational frequency of 2,6-dimethylphenyl isocyanide (2,6
      DMPI) can serve as a distinctive reporter for capturing the nucleation of Pt on
      the edges of Ag nanocubes in the aqueous solution containing a Pt precursor,
      ascorbic acid, and poly(vinylpyrrolidone) under ambient conditions. Our success
      relies on the difference in stretching frequency for the NC bond when the
      isocyanide group binds to the Ag and Pt atoms. Specifically, sigma donation from
      the antibonding sigma* orbital of the -NC group to the d-band of Ag would
      strengthen the NC bond, blue shifting the stretching frequency. In contrast, pi
      back-donation from the d-band of Pt to the pi* antibonding orbital of the -NC
      group would weaken the NC bond, leading to a red shift of stretching frequency.
      Therefore, it is feasible to in situ characterize the outermost surface that
      consists of both newly deposited Pt atoms and remaining Ag atoms by following the
      stretching frequencies and intensities of 2,6-DMPI in real time. Because the SERS
      hot spots on the edges of Ag nanocubes coincide with the {110} facets preferred
      for the nucleation of Pt atoms, this technique is capable of resolving 27 Pt
      atoms being deposited on each edge of a 39 nm Ag nanocube in the original growth
      solution. Collectively, in situ SERS, with its consummate sensitivity to
      molecular structure and bonding of isocyanide-based molecular probe, could
      elucidate the mechanistic details involved in the seeded overgrowth of a
      catalytically significant metal, such as Pt, Pd, Ir, Rh, and Ru, on the surface
      of a Ag or Au nanocrystal seed.

PMID- 28437069
TI  - A New Look at the Structural and Magnetic Properties of Potassium Neptunate
      K2NpO4 Combining XRD, XANES Spectroscopy, and Low-Temperature Heat Capacity.
AB  - The physicochemical properties of the potassium neptunate K2NpO4 have been
      investigated in this work using X-ray diffraction, X-ray absorption near edge
      structure (XANES) spectroscopy at the Np-L3 edge, and low-temperature heat
      capacity measurements. A Rietveld refinement of the crystal structure is reported
      for the first time. The Np(VI) valence state has been confirmed by the XANES
      data, and the absorption edge threshold of the XANES spectrum has been correlated
      to the Mossbauer isomer shift value reported in the literature. The standard
      entropy and heat capacity of K2NpO4 have been derived at 298.15 K from the low
      temperature heat capacity data. The latter suggest the existence of a magnetic
      ordering transition around 25.9 K, most probably of the ferromagnetic type.

PMID- 28437070
TI  - Large-Scale Synthesis of Carbon-Shell-Coated FeP Nanoparticles for Robust
      Hydrogen Evolution Reaction Electrocatalyst.
AB  - A highly active and stable non-Pt electrocatalyst for hydrogen production has
      been pursued for a long time as an inexpensive alternative to Pt-based catalysts.
      Herein, we report a simple and effective approach to prepare high-performance
      iron phosphide (FeP) nanoparticle electrocatalysts using iron oxide nanoparticles
      as a precursor. A single-step heating procedure of polydopamine-coated iron oxide
      nanoparticles leads to both carbonization of polydopamine coating to the carbon
      shell and phosphidation of iron oxide to FeP, simultaneously. Carbon-shell-coated
      FeP nanoparticles show a low overpotential of 71 mV at 10 mA cm-2, which is
      comparable to that of a commercial Pt catalyst, and remarkable long-term
      durability under acidic conditions for up to 10 000 cycles with negligible
      activity loss. The effect of carbon shell protection was investigated both
      theoretically and experimentally. A density functional theory reveals that
      deterioration of catalytic activity of FeP is caused by surface oxidation.
      Extended X-ray absorption fine structure analysis combined with electrochemical
      test shows that carbon shell coating prevents FeP nanoparticles from oxidation,
      making them highly stable under hydrogen evolution reaction operation conditions.
      Furthermore, we demonstrate that our synthetic method is suitable for mass
      production, which is highly desirable for large-scale hydrogen production.

PMID- 28437071
TI  - Revealing the Initial Reaction Behavior in the Continuous Synthesis of Metal
      Organic Frameworks Using Real-Time Synchrotron X-ray Analysis.
AB  - In recent years, continuous process technologies have attracted increasing
      attention, as a means of overcoming limitations in the repeatability and
      reproducibility of metal-organic framework (MOF) synthesis. Research in this
      area, however, has neglected to provide insight into the phenomenon leading to
      the formation of MOFs. In this work, we report the adaption of high-energy
      synchrotron powder X-ray diffraction analysis to a continuous ZIF-8 production
      process for online monitoring of the reaction behavior and crystallite formation
      during the first seconds of the MOF synthesis. It was confirmed that a diffusion
      controlled growth mechanism was accelerated by additional radial diffusion
      processes in the flow reactor. Kinetic analysis revealed a rapid crystallite
      formation of ZIF-8, which was completed after 8 s of reaction time and which
      offers the potential for future process optimization.

PMID- 28437072
TI  - The Single Disulfide-Directed beta-Hairpin Fold. Dynamics, Stability, and
      Engineering.
AB  - Grafting bioactive peptide sequences onto small cysteine-rich scaffolds is a
      promising strategy for enhancing their stability and value as novel peptide-based
      therapeutics. However, correctly folded disulfide-rich peptides can be
      challenging to produce by either recombinant or synthetic means. The single
      disulfide-directed beta-hairpin (SDH) fold, first observed in contryphan-Vc1,
      provides a potential alternative to complex disulfide-rich scaffolds. We have
      undertaken recombinant production of full-length contryphan-Vc1 (rCon-Vc1[Z1Q])
      and a truncated analogue (rCon-Vc11-22[Z1Q]), analyzed the backbone dynamics of
      rCon-Vc1[Z1Q], and probed the conformational and proteolytic stability of these
      peptides to evaluate the potential of contryphan-Vc1 as a molecular scaffold.
      Backbone 15N relaxation measurements for rCon-Vc1[Z1Q] indicate that the N
      terminal domain of the peptide is ordered up to Thr19, whereas the remainder of
      the C-terminal region is highly flexible. The solution structure of truncated
      rCon-Vc11-22[Z1Q] was similar to that of the full-length peptide, indicating that
      the flexible C-terminus does not have any effect on the structured domain of the
      peptide. Contryphan-Vc1 exhibited excellent proteolytic stability against trypsin
      and chymotrypsin but was susceptible to pepsin digestion. We have investigated
      whether contryphan-Vc1 can accept a bioactive epitope while maintaining the
      structure of the peptide by introducing peptide sequences based on the DINNN
      motif of inducible nitric oxide synthase. We show that sCon-Vc11-22[NNN12-14]
      binds to the iNOS-binding protein SPSB2 with an affinity of 1.3 MUM while
      maintaining the SDH fold. This study serves as a starting point in utilizing the
      SDH fold as a peptide scaffold.

PMID- 28437074
TI  - Many-Body Energy Decomposition with Basis Set Superposition Error Corrections.
AB  - The problem of performing many-body decompositions of energy is considered in the
      case when BSSE corrections are also performed. It is discussed that the two
      different schemes that have been proposed go back to the two different
      interpretations of the original Boys-Bernardi counterpoise correction scheme. It
      is argued that from the physical point of view the "hierarchical" scheme of
      Valiron and Mayer should be preferred and not the scheme recently discussed by
      Ouyang and Bettens, because it permits the energy of the individual monomers and
      all the two-body, three-body, etc. energy components to be free of unphysical
      dependence on the arrangement (basis functions) of other subsystems in the
      cluster.

PMID- 28437075
TI  - Fluorescent Photoswitchable Diarylethenes for Biolabeling and Single-Molecule
      Localization Microscopies with Optical Superresolution.
AB  - A modular assembly of water-soluble diarylethenes (DAEs), applicable as
      biomarkers for optical nanoscopy, is reported. Reversibly photoswitchable 1,2
      bis(2-alkyl-6-phenyl-1-benzothiophene-1,1-dioxide-3-yl)perfluorocyclopentenes
      possessing a fluorescent "closed" form were decorated with one or two methoxy
      group(s) attached to the para-position(s) of phenyl ring(s) and two, four, or
      eight carboxylic acid groups. Antibody conjugates of these DAEs feature low
      aggregation, efficient photoswitching in aqueous buffers, specific staining of
      cellular structures, and photophysical properties (high emission efficiencies and
      low cycloreversion quantum yields) enabling their application in superresolution
      microscopy. Images of tubulin, vimentin, and nuclear pore complexes are
      presented. The superresolution images can also be acquired by using solely 488 nm
      light without additional photoactivation with UV light. These DAEs exhibit
      reversible photoswitching without requiring any additives to the imaging media
      and open new paths toward the modular design of fluorescent dyes for bioimaging
      with optical superresolution.

PMID- 28437073
TI  - Intermotif Communication Induces Hierarchical Ca2+ Filling of Caldendrin.
AB  - A crucial event in calcium signaling is the transition of a calcium sensor from
      the apo (Ca2+ free) to the holo (Ca2+-saturated) state. Caldendrin (CDD) is a
      neuronal Ca2+-binding protein with two functional (EF3 and EF4) and two atypical
      (EF1 and EF2), non-Ca2+-binding EF-hand motifs. During the transition from the
      apo to the holo state, guided by the stepwise filling of Ca2+, the protein passes
      through distinct states and acquires a stable conformational state when only EF3
      is occupied by Ca2+. This state is characterized by a Ca2+-derived structural
      gain in EF3 with destabilization of the EF4 motif. At higher Ca2+ levels, when
      Ca2+ fills in EF4, the motif regains stability. EF3 controls initial Ca2+ binding
      and dictates structural destabilization of EF4. It is likely that this unexpected
      intermotif communication will have an impact on Ca2+-dependent target
      interactions.

PMID- 28437076
TI  - Series of ZnSn(OH)6 Polyhedra: Enhanced CO2 Dissociation Activation and Crystal
      Facet-Based Homojunction Boosting Solar Fuel Synthesis.
AB  - A series of ZnSn(OH)6 polyhedra are successfully explored with well-controlled
      area ratio of the exposed {100} and {111} facets. Band alignment of the exposed
      facet-based homojunction of the elegant polyhedron facilitates spatial separation
      of photogenerated electrons and holes on {111} and {100} surfaces, respectively.
      Optimal area ratio of {100} to {111} is the prerequisite for pronounced CO2
      photocatalytic performance of high-symmetry cuboctahedra into methane (CH4). The
      synergistic effect of the excess electron accumulation and simultaneously the
      enhanced CO2 absorption and low dissociation activation energy on {111} reduction
      sites promote the yield of CO2 photocatalytic conversion product.

PMID- 28437078
TI  - A Step toward High-Energy Silicon-Based Thin Film Lithium Ion Batteries.
AB  - The next generation of lithium ion batteries (LIBs) with increased energy density
      for large-scale applications, such as electric mobility, and also for small
      electronic devices, such as microbatteries and on-chip batteries, requires
      advanced electrode active materials with enhanced specific and volumetric
      capacities. In this regard, silicon as anode material has attracted much
      attention due to its high specific capacity. However, the enormous volume changes
      during lithiation/delithiation are still a main obstacle avoiding the broad
      commercial use of Si-based electrodes. In this work, Si-based thin film
      electrodes, prepared by magnetron sputtering, are studied. Herein, we present a
      sophisticated surface design and electrode structure modification by amorphous
      carbon layers to increase the mechanical integrity and, thus, the electrochemical
      performance. Therefore, the influence of amorphous C thin film layers, either
      deposited on top (C/Si) or incorporated between the amorphous Si thin film layers
      (Si/C/Si), was characterized according to their physical and electrochemical
      properties. The thin film electrodes were thoroughly studied by means of
      electrochemical impedance spectroscopy, Raman spectroscopy, X-ray photoelectron
      spectroscopy, and atomic force microscopy. We can show that the silicon thin film
      electrodes with an amorphous C layer showed a remarkably improved electrochemical
      performance in terms of capacity retention and Coulombic efficiency. The C layer
      is able to mitigate the mechanical stress during lithiation of the Si thin film
      by buffering the volume changes and to reduce the loss of active lithium during
      solid electrolyte interphase formation and cycling.

PMID- 28437077
TI  - Peptide and Protein Dynamics and Low-Temperature/DNP Magic Angle Spinning NMR.
AB  - In DNP MAS NMR experiments at ~80-110 K, the structurally important -13CH3 and 
      15NH3+ signals in MAS spectra of biological samples disappear due to the
      interference of the molecular motions with the 1H decoupling. Here we investigate
      the effect of these dynamic processes on the NMR line shapes and signal
      intensities in several typical systems: (1) microcrystalline APG, (2) membrane
      protein bR, (3) amyloid fibrils PI3-SH3, (4) monomeric alanine-CD3, and (5) the
      protonated and deuterated dipeptide N-Ac-VL over 78-300 K. In APG, the three-site
      hopping of the Ala-Cbeta peak disappears completely at 112 K, concomitant with
      the attenuation of CP signals from other 13C's and 15N's. Similarly, the 15N
      signal from Ala-NH3+ disappears at ~173 K, concurrent with the attenuation in CP
      experiments of other 15N's as well as 13C's. In bR and PI3-SH3, the methyl groups
      are attenuated at ~95 K, while all other 13C's remain unaffected. However, both
      systems exhibit substantial losses of intensity at ~243 K. Finally, with spectra
      of Ala and N-Ac-VL, we show that it is possible to extract site specific dynamic
      data from the temperature dependence of the intensity losses. Furthermore, 2H
      labeling can assist with recovering the spectral intensity. Thus, our study
      provides insight into the dynamic behavior of biological systems over a wide
      range of temperatures, and serves as a guide to optimizing the sensitivity and
      resolution of structural data in low temperature DNP MAS NMR spectra.

PMID- 28437079
TI  - Hierarchical Porous Polybenzimidazole Microsieves: An Efficient Architecture for
      Anhydrous Proton Transport via Polyionic Liquids.
AB  - Liquid-induced phase-separation micromolding (LIPSMUM) has been successfully used
      for manufacturing hierarchical porous polybenzimidazole (HPBI) microsieves (42
      46% porosity, 30-40 MUm thick) with a specific pore architecture (pattern of
      macropores: ~9 MUm in size, perforated, dispersed in a porous matrix with a 50
      100 nm pore size). Using these microsieves, proton-exchange membranes were
      fabricated by the infiltration of a 1H-3-vinylimidazolium
      bis(trifluoromethanesulfonyl)imide liquid and divinylbenzene (as a cross-linker),
      followed by in situ UV polymerization. Our approach relies on the separation of
      the ion conducting function from the structural support function. Thus, the
      polymeric ionic liquid (PIL) moiety plays the role of a proton conductor, whereas
      the HPBI microsieve ensures the mechanical resistance of the system. The
      influence of the porous support architecture on both proton transport performance
      and mechanical strength has been specifically investigated by means of comparison
      with straight macroporous (36% porosity) and randomly nanoporous (68% porosity)
      PBI counterparts. The most attractive results were obtained with the poly[1-(3H
      imidazolium)ethylene]bis(trifluoromethanesulfonyl)imide PIL cross-linked with 1%
      divinylbenzene supported on HPBI membranes with a 21-MUm-thick skin layer,
      achieving conductivity values up to 85 mS cm-1 at 200  degrees C under anhydrous
      conditions and in the absence of mineral acids.

PMID- 28437080
TI  - Comparison of Tumor Penetration of Podophyllotoxin-Carboxymethylcellulose
      Conjugates with Various Chemical Compositions in Tumor Spheroid Culture and In
      Vivo Solid Tumor.
AB  - Polymer conjugation is an attractive approach for delivering insoluble and highly
      toxic drugs to tumors. However, most reports in the literature only disclose the
      optimal composition without emphasizing rational design or composition
      optimization to achieve maximized biological effects. In this study, we aimed to
      demonstrate that composition of a polymer conjugate would determine its
      physiochemical characteristics, tumor penetration, and, ultimately, the in vivo
      efficacy. We also aimed to examine whether the tumor spheroid model could
      generate comparable results with the in vivo tumor model in terms of tumor
      penetration and efficacy of the various polymer conjugates. We have designed a
      polymer conjugate delivery system for a chemotherapeutic drug podophyllotoxin
      (PPT) by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated
      carboxymethyl cellulose to yield conjugates containing various amounts of PPT and
      PEG. Depending on the composition, these conjugates self-assembled into
      nanoparticles (NPs) with different physicochemical properties. Conjugates with an
      increased PPT content formed particles with an increased diameter. In the present
      study, we selected three conjugates representing compositions containing high,
      medium, and low drug content, and compared their particle formation, drug release
      kinetics, their ability to penetrate tumor spheroid and in vivo s.c. tumor, and
      finally their antitumor efficacy in spheroid culture and an in vivo s.c. tumor
      model. We found that the low drug content conjugate formed smaller NPs (20 nm)
      compared to the high drug content conjugates (30-120 nm), and displayed faster
      drug release kinetics (5%/day vs 1-3%/day), improved tumor penetration, and
      enhanced antitumor efficacy in both the spheroid model and s.c. tumor model. In
      particular, the low drug content conjugate preferentially accumulated in the
      hypovascular region within the tumor, inducing complete regression of s.c. tumors
      and the metastasis to the lungs. Our data indicate composition optimization is
      needed to select the optimal conjugate, and tumor spheroid culture is a robust
      screening tool to help select the optimal formulation.

PMID- 28437081
TI  - Silicon-Induced UV Transparency in Phosphate Glasses and Its Application to the
      Enhancement of the UV Type B Emission of Gd3.
AB  - The silicon route to improve the ultraviolet (UV) transparency in phosphate
      glasses is investigated and further exploited to enhance the UV type B (280-320
      nm) emission of gadolinium(III) relevant for biomedical applications. The glasses
      were synthesized with a barium phosphate composition by melt-quenching in ambient
      atmosphere and the optical properties investigated by optical absorption and
      photoluminescence (PL) spectroscopy including emission decay kinetics. An
      improvement in the UV transparency was gradually developed for the glasses melted
      merely with increasing amounts of Si powder. A particular PL in the visible was
      also exhibited for such glasses under excitation at 275 nm, consistent with the
      presence of Si-induced defects. For Si-Gd codoped glasses, the UV transparency
      was likewise manifested, while the UV emission from Gd3+ around 312 nm was
      enhanced with the increase in Si concentration (up to ~6.7 times). Moreover,
      along with the Gd3+ PL intensity enhancement, a linear correlation was revealed
      between the increase in decay times for the Gd3+6P7/2-emitting state and the
      amount of silicon. It is then suggested that the improved PL properties of
      gadolinium(III) originate from the increased UV transparency of the host and the
      consequent precluding of a nonradiative energy transfer from Gd3+ to the matrix.
      Accordingly, a role of Si as PL quenching inhibitor is supported. The
      demonstrated efficacy of the Si-Gd codoping concept realized by a facile glass
      synthesis procedure may appeal to the application of the UV-emitting glasses for
      phototherapy lamps.

PMID- 28437083
TI  - Dual Plug-and-Display Synthetic Assembly Using Orthogonal Reactive Proteins for
      Twin Antigen Immunization.
AB  - Engineering modular platforms to control biomolecular architecture can advance
      both the understanding and the manipulation of biological systems. Icosahedral
      particles uniformly displaying single antigens stimulate potent immune activation
      and have been successful in various licensed vaccines. However, it remains
      challenging to display multiple antigens on a single particle and to induce
      broader immunity protective across strains or even against distinct diseases.
      Here, we design a dually addressable synthetic nanoparticle by engineering the
      multimerizing coiled-coil IMX313 and two orthogonally reactive split proteins.
      SpyCatcher protein forms an isopeptide bond with SpyTag peptide through
      spontaneous amidation. SnoopCatcher forms an isopeptide bond with SnoopTag
      peptide through transamidation. SpyCatcher-IMX-SnoopCatcher provides a modular
      platform, whereby SpyTag-antigen and SnoopTag-antigen can be multimerized on
      opposite faces of the particle simply upon mixing. We demonstrate efficient
      derivatization of the platform with model proteins and complex pathogen-derived
      antigens. SpyCatcher-IMX-SnoopCatcher was expressed in Escherichia coli and was
      resilient to lyophilization or extreme temperatures. For the next generation of
      malaria vaccines, blocking the transmission of the parasite from human to
      mosquito is an important goal. SpyCatcher-IMX-SnoopCatcher multimerization of the
      leading transmission-blocking antigens Pfs25 and Pfs28 greatly enhanced the
      antibody response to both antigens in comparison to the monomeric proteins. This
      dual plug-and-display architecture should help to accelerate vaccine development
      for malaria and other diseases.

PMID- 28437082
TI  - High-Efficiency "-1" and "-2" Ribosomal Frameshiftings Revealed by Force
      Spectroscopy.
AB  - Ribosomal frameshifting is a rare but ubiquitous process that is being studied
      extensively. Meanwhile, frameshifting motifs without any secondary mRNA
      structures were identified but rarely studied experimentally. We report
      unambiguous observation of highly efficient "-1" and "-2" frameshiftings on a
      GA7G slippery mRNA without the downstream secondary structure, using force
      induced remnant magnetization spectroscopy combined with unique probing schemes.
      The result represents the first experimental evidence of multiple frameshifting
      steps. It is also one of the rare reports of the "-2" frameshifting. Our assay
      removed the ambiguity of transcriptional slippage involvement in other
      frameshifting assays. Two significant insights for the frameshifting mechanism
      were revealed. First, EF-G.GTP is indispensable to frameshifting. Although
      EFG.GDPCP has been shown to prompt translocation before, we found that it could
      not induce frameshifting. This implies that the GTP hydrolysis is responsible for
      the codon-anticodon re-pairing in frameshifting, which corroborates our previous
      mechanical force measurement of EF-G.GTP. Second, translation in all three
      reading frames of the slippery sequence can be induced by the corresponding in
      frame aminoacyl tRNAs. Although A-site tRNA is known to affect the partition
      between "0" and "-1" frameshifting, it has not been reported that all three
      reading frames can be translated by their corresponding tRNAs. The in vitro
      results were confirmed by toe-printing assay and protein sequencing.

PMID- 28437084
TI  - Affinity Binding of EMR2 Expressing Cells by Surface-Grafted Chondroitin Sulfate
      B.
AB  - The propensity of glycosaminoglycans to mediate cell-cell and cell-matrix
      interactions opens the door to capture cells, including circulating blood cells,
      onto biomaterial substrates. Chondroitin sulfate (CS)-B is of particular
      interest, since it interacts with the receptor (EGF)-like module-containing mucin
      like hormone receptor-like 2 precursor (EMR2) displayed on the surface of
      leukocytes and endothelial progenitor cells. Herein, CS-B and its isomer CS-A
      were covalently immobilized onto heptylamine plasma polymer films via three
      different binding chemistries to develop platform technology for the capture of
      EMR2 expressing cells onto solid carriers. Surface characterization verified the
      successful immobilization of both glycosaminoglycans. The EMR2 expressing human
      myeloid cell line U937 preferentially bound onto CS-B-modified substrates, and
      U937 cells preincubated with CS-B in solution exhibited reduced affinity for the
      substrate. The direct capture of hematopoietic and blood-circulating endothelial
      cell types via a glycosaminoglycan-binding surface receptor opens an unexplored
      route for the development of biomaterials targeted at these cell types.

PMID- 28437085
TI  - A Short Covalent Synthesis of an All-Carbon-Ring [2]Rotaxane.
AB  - While the current supramolecular syntheses of [2]rotaxanes are generally
      efficient, the final product always retains the functional groups required for
      non-covalent preorganization. A short and high-yielding covalent-template
      assisted approach is reported for the synthesis of a [2]rotaxane. A terephthalic
      acid template core preorganizes the covalently connected ring precursor fragments
      to induce a clipping-type cyclization over the thread moiety. Cleavage of the
      temporary ester bonds that connect the ring and thread fragments liberates the
      [2]rotaxane.

PMID- 28437086
TI  - The Skyrmion Switch: Turning Magnetic Skyrmion Bubbles on and off with an
      Electric Field.
AB  - Nanoscale magnetic skyrmions are considered as potential information carriers for
      future spintronics memory and logic devices. Such applications will require the
      control of their local creation and annihilation, which involves so far solutions
      that are either energy consuming or difficult to integrate. Here we demonstrate
      the control of skyrmion bubbles nucleation and annihilation using electric field
      gating, an easily integrable and potentially energetically efficient solution. We
      present a detailed stability diagram of the skyrmion bubbles in a Pt/Co/oxide
      trilayer and show that their stability can be controlled via an applied electric
      field. An analytical bubble model with the Dzyaloshinskii-Moriya interaction
      imbedded in the domain wall energy accounts for the observed electrical skyrmion
      switching effect. This allows us to unveil the origin of the electrical control
      of skyrmions stability and to show that both magnetic dipolar interaction and the
      Dzyaloshinskii-Moriya interaction play an important role in the skyrmion bubble
      stabilization.

PMID- 28437087
TI  - Al-Coated Conductive Fibrous Filter with Low Pressure Drop for Efficient
      Electrostatic Capture of Ultrafine Particulate Pollutants.
AB  - Here, we demonstrate a new strategy of air filtration based on an Al-coated
      conductive fibrous filter for high efficient nanoparticulate removals. The
      conductive fibrous filter was fabricated by a direct decomposition of Al
      precursor ink, AlH3{O(C4H9)2}, onto surfaces of a polyester air filter via a cost
      effective and scalable solution-dipping process. The prepared conductive filters
      showed a low sheet resistance (<1.0 Omega sq-1), robust mechanical durability and
      high oxidative stability. By electrostatic force between the charged fibers and
      particles, the ultrafine particles of 30-400 nm in size were captured with a
      removal efficiency of ~99.99%. Moreover, the conductive filters exhibited
      excellent performances in terms of the pressure drop (~4.9 Pa at 10 cm s-1),
      quality factor (~2.2 Pa-1 at 10 cm s-1), and dust holding capacity (12.5 MUg mm
      2). After being cleaned by water, the filtration efficiency and pressure drop of
      the conductive filter was perfectly recovered, which indicates its good
      recyclability. It is expected that these promising features make the conductive
      fibrous filter have a great potential for use in low-cost and energy-efficient
      air cleaning devices as well as other relevant research areas.

PMID- 28437089
TI  - sigma N-C Bond Difunctionalization in Bridged Twisted Amides: Sew-and-Cut
      Activation Approach to Functionalized Isoquinolines.
AB  - A rare example of highly selective sigma N-C bond difunctionalization in bridged
      twisted lactams through N-C cleavage has been achieved. In combination with the
      intramolecular Heck cyclization, this method affords a two-step bond
      reorganization event ("sew-and-cut") to access functionalized isoquinoline ring
      systems directly with high atom economy. C-H bond functionalizations directed by
      a weakly coordinating bridged amide bond increase scaffold diversity. Preliminary
      mechanistic studies on the effect of amide distortion and the role of
      electrophile in this unusual sigma N-C amide difunctionalization are described.

PMID- 28437088
TI  - HILAQ: A Novel Strategy for Newly Synthesized Protein Quantification.
AB  - Here we describe a new strategy, HILAQ (Heavy Isotope Labeled Azidohomoalanine
      Quantification), to rapidly quantify the molecular vulnerability profile to
      oxytosis, which is an oxidative stress-induced programed cell death pathway that
      has been reported to be involved in aging and neurodegenerative diseases. HILAQ
      was able to quantify 1962 newly synthesized proteins (NSPs) after 1 h of pulse
      labeling in HEK293T cell line, while 353 proteins were quantified using the
      previously published QuaNCAT protocol. HILAQ was successfully applied to the HT22
      oxytosis model. 226 proteins were found to have a two-fold change in abundance,
      and 108 proteins were enriched in the cell death pathway, demonstrating the
      utility of HT22 cells as a tool to study the molecular details of cell death
      involved in neurodegenerative diseases. The HILAQ strategy simplifies the
      analysis of newly synthesized proteomes through the use of isobaric labels and
      achieves higher sensitivity than previously published methods.

PMID- 28437091
TI  - Speeding up Early Drug Discovery in Antiviral Research: A Fragment-Based in
      Silico Approach for the Design of Virtual Anti-Hepatitis C Leads.
AB  - Hepatitis C constitutes an unresolved global health problem. This infectious
      disease is caused by the hepatotropic hepatitis C virus (HCV), and it can lead to
      the occurrence of life-threatening medical conditions, such as cirrhosis and
      liver cancer. Nowadays, major clinical concerns have arisen because of the
      appearance of multidrug resistance (MDR) and the side effects especially
      associated with long-term treatments. In this work, we report the first
      multitasking model for quantitative structure-biological effect relationships
      (mtk-QSBER), focused on the simultaneous exploration of anti-HCV activity and in
      vitro safety profiles related to the absorption, distribution, metabolism,
      elimination, and toxicity (ADMET). The mtk-QSBER model was created from a data
      set formed by 40 158 cases, displaying accuracy higher than 95% in both training
      and prediction (test) sets. Several molecular fragments were selected, and their
      quantitative contributions to anti-HCV activity and ADMET profiles were
      calculated. By combining the analysis of the fragments with positive
      contributions and the physicochemical meanings of the different molecular
      descriptors in the mtk-QSBER, six new molecules were designed. These new
      molecules were predicted to exhibit potent anti-HCV activity and desirable in
      vitro ADMET properties. In addition, the designed molecules have good
      druglikeness according to the Lipinski's rule of five and its variants.

PMID- 28437090
TI  - Improved Photodynamic Therapy Efficacy of Protoporphyrin IX-Loaded Polymeric
      Micelles Using Erlotinib Pretreatment.
AB  - Photodynamic therapy (PDT) has attracted widespread attention in recent years as
      a noninvasive and highly selective approach for cancer treatment. We have
      previously reported a significant increase in the 90-day complete response rate
      when tumor-bearing mice are treated with the epidermal growth factor receptor
      (EGFR) inhibitor erlotinib prior to PDT with the photosensitizer benzoporphyrin
      derivative monoacid ring A (BPD-MA) compared to treatment with PDT alone. To
      further explore this strategy for anticancer therapy and clinical practice, we
      tested whether pretreatment with erlotinib also exhibited a synergistic
      therapeutic effect with a nanocarrier containing the clinically relevant
      photosensitizer protoporphyrin IX (PpIX). The PpIX was encapsulated within
      biodegradable polymeric micelles formed from the amphiphilic block copolymer
      poly(ethylene glycol)-polycaprolactone (PEG-PCL). The obtained micelles were
      characterized systematically in vitro. Further, an in vitro cytotoxicity study
      showed that PDT with PpIX loaded micelles did exhibit a synergistic effect when
      combined with erlotinib pretreatment. Considering the distinct advantages of
      polymeric nanocarriers in vivo, this study offers a promising new approach for
      the improved treatment of localized tumors. The strategy developed here has the
      potential to be extended to other photosensitizers currently used in the clinic
      for photodynamic therapy.

PMID- 28437092
TI  - Facile Quenching and Spatial Patterning of Cylooctynes via Strain-Promoted Alkyne
      Azide Cycloaddition of Inorganic Azides.
AB  - Little is known about the reactivity of strain-promoted alkyne-azide
      cycloaddition (SPAAC) reagents with inorganic azides. We explore the reactions of
      a variety of popular SPAAC reagents with sodium azide and hydrozoic acid. We find
      that the reactions proceed in water at rates comparable to those with organic
      azides, yielding in all cases a triazole adduct. The azide ion's utility as a
      cyclooctyne quenching reagent is demonstrated by using it to spatially pattern
      uniformly doped hydrogels. The facile quenching of cyclooctynes demonstrated here
      should be useful in other bioorthogonal ligation techniques in which cyclooctynes
      are employed, including SPANC, Diels-Alder, and thiol-yne.

PMID- 28437093
TI  - A Pathogen-Specific Cargo Delivery Platform Based on Mesoporous Silica
      Nanoparticles.
AB  - We present a synthetic approach to a highly pathogen-selective detection and
      delivery platform based on the interaction of an antibody nanovalve with a
      tetrasaccharide from the O-antigen of the lipopolysaccharide (LPS) of Francisella
      tularensis bacteria, a Tier 1 Select Agent of bioterrorism. Different design
      considerations are explored, and proof-of-concept for highly pathogen-specific
      cargo release from mesoporous silica nanoparticles is demonstrated by comparisons
      of the release of a signal transducer and model drug by LPS from F. tularensis vs
      Pseudomonas aeruginosa and by F. tularensis live bacteria vs the closely related
      bacterium Francisella novocida. In addition to the specific response to a
      biowarfare agent, treatment of infectious diseases in general could benefit
      tremendously from a delivery platform that releases its antibiotic payload only
      at the site of infection and only in the presence of the target pathogen, thereby
      minimizing off-target toxicities.

PMID- 28437094
TI  - Rational Design of an Ultrasensitive Quorum-Sensing Switch.
AB  - One of the purposes of synthetic biology is to develop rational methods that
      accelerate the design of genetic circuits, saving time and effort spent on
      experiments and providing reliably predictable circuit performance. We applied a
      reverse engineering approach to design an ultrasensitive transcriptional quorum
      sensing switch. We want to explore how systems biology can guide synthetic
      biology in the choice of specific DNA sequences and their regulatory relations to
      achieve a targeted function. The workflow comprises network enumeration that
      achieves the target function robustly, experimental restriction of the obtained
      candidate networks, global parameter optimization via mathematical analysis,
      selection and engineering of parts based on these calculations, and finally,
      circuit construction based on the principles of standardization and
      modularization. The performance of realized quorum-sensing switches was in good
      qualitative agreement with the computational predictions. This study provides
      practical principles for the rational design of genetic circuits with targeted
      functions.

PMID- 28437095
TI  - Reliability of Single Crystal Silver Nanowire-Based Systems: Stress Assisted
      Instabilities.
AB  - Time-dependent mechanical characterization of nanowires is critical to understand
      their long-term reliability in applications, such as flexible-electronics and
      touch screens. It is also of great importance to develop a theoretical framework
      for experimentation and analysis on the mechanics of nanowires under time
      dependent loading conditions, such as stress-relaxation and fatigue. Here, we
      combine in situ scanning electron microscope (SEM)/transmission electron
      microscope (TEM) tests with atomistic and phase-field simulations to understand
      the deformation mechanisms of single crystal silver nanowires held under constant
      strain. We observe that the nanowires initially undergo stress-relaxation, where
      the stress reduces with time and saturates after some time period. The stress
      relaxation process occurs due to the formation of few dislocations and stacking
      faults. Remarkably, after a few hours the nanowires rupture suddenly. The reason
      for this abrupt failure of the nanowire was identified as stress-assisted
      diffusion, using phase-field simulations. Under a large applied strain, diffusion
      leads to the amplification of nanowire surface perturbation at long wavelengths
      and the nanowire fails at the stress-concentrated thin cross-sectional regions.
      An analytical analysis on the competition between the elastic energy and the
      surface energy predicts a longer time to failure for thicker nanowires than
      thinner ones, consistent with our experimental observations. The measured time to
      failure of nanowires under cyclic loading conditions can also be explained in
      terms of this mechanism.

PMID- 28437096
TI  - Importance of MM Polarization in QM/MM Studies of Enzymatic Reactions: Assessment
      of the QM/MM Drude Oscillator Model.
AB  - : For accurate quantum mechanics/molecular mechanics (QM/MM) studies of enzymatic
      reactions, it is desirable to include MM polarization, for example by using the
      Drude oscillator (DO) model. For a long time, such studies were hampered by the
      lack of well-tested polarizable force fields for proteins. Following up on a
      recent preliminary QM/MM-DO assessment (J. Chem. THEORY: Comput. 2014, 10, 1795
      1809), we now report a comprehensive investigation of the effects of MM
      polarization on two enzymatic reactions, namely the Claisen rearrangement in
      chorismate mutase and the hydroxylation reaction in p-hydroxybenzoate
      hydroxylase, using the QM/CHARMM-DO model and two QM methods (B3LYP, OM2). We
      compare the results from extensive geometry optimizations and free energy
      simulations at the QM/MM-DO level to those obtained from analogous calculations
      at the conventional QM/MM level.

PMID- 28437098
TI  - Interaction of Fibrin with the Very Low-Density Lipoprotein (VLDL) Receptor:
      Further Characterization and Localization of the VLDL Receptor-Binding Site in
      Fibrin betaN-Domains.
AB  - Our recent study revealed that fibrin and the very low-density lipoprotein
      receptor (VLDLR) interact with each other through a pair of fibrin betaN-domains
      and CR domains of the receptor and this interaction promotes transendothelial
      migration of leukocytes and thereby inflammation. The major objectives of this
      study were to further clarify the molecular mechanism of fibrin-VLDLR interaction
      and to identify amino acid residues in the betaN-domains involved in this
      interaction. Our binding experiments with the (beta15-66)2 fragment, which
      corresponds to a pair of fibrin betaN-domains, and the VLDLR(1-8) fragment,
      consisting of eight CR domains of VLDLR, revealed that interaction between them
      strongly depends on ionic strength and chemical modification of all Lys or Arg
      residues in (beta15-66)2 results in abrogation of this interaction. To identify
      which of these residues are involved in the interaction, we mutated all Lys or
      Arg residues in each of the three positively charged Lys/Arg clusters of the
      (beta15-66)2 fragment, as well as single Arg17 and Arg30, and tested the affinity
      of the mutants obtained for VLDLR(1-8) by an enzyme-linked immunosorbent assay
      and surface plasmon resonance. The experiments revealed that the second and third
      Lys/Arg clusters make the major contribution to this interaction while the
      contribution of the first cluster is moderate. The results obtained suggest that
      interaction between fibrin and the VLDL receptor employs the "double-Lys/Arg"
      recognition mode previously proposed for the interaction of the LDL receptor
      family members with their ligands. They also provide valuable information for the
      development of highly specific peptide-based inhibitors of fibrin-VLDLR
      interaction.

PMID- 28437099
TI  - Surfactant 1-Hexadecyl-3-methylimidazolium Chloride Can Convert One-Dimensional
      Viologen Bromoplumbate into Zero-Dimensional.
AB  - A zero-dimensional N,N'-dibutyl-4,4'-dipyridinium bromoplumbate, [BV]6[Pb9Br30],
      with unusual discrete [Pb9Br30]12- anionic clusters was prepared via a facile
      surfactant-mediated solvothermal process. This bromoplumbate exhibits a narrower
      optical band gap relative to the congeneric one-dimensional viologen
      bromoplumbates.

PMID- 28437097
TI  - Total Syntheses of Vancomycin-Related Glycopeptide Antibiotics and Key Analogues.
AB  - A review of efforts that have provided total syntheses of vancomycin and related
      glycopeptide antibiotics, their agylcons, and key analogues is provided. It is a
      tribute to developments in organic chemistry and the field of organic synthesis
      that not only can molecules of this complexity be prepared today by total
      synthesis but such efforts can be extended to the preparation of previously
      inaccessible key analogues that contain deep-seated structural changes. With the
      increasing prevalence of acquired bacterial resistance to existing classes of
      antibiotics and with the emergence of vancomycin-resistant pathogens (VRSA and
      VRE), the studies pave the way for the examination of synthetic analogues
      rationally designed to not only overcome vancomycin resistance but provide the
      foundation for the development of even more powerful and durable antibiotics.

PMID- 28437100
TI  - Reparameterization of Solute-Solute Interactions for Amino Acid-Sugar Systems
      Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations.
AB  - AMBER/GLYCAM and CHARMM are popular force fields for simulations of amino acids
      and sugars. Here we report excessively attractive amino acid-sugar interactions
      in both force fields, and corrections to nonbonded interactions that match
      experimental osmotic pressures of mixed aqueous solutions of diglycine and
      sucrose. The modified parameters also improve the DeltaGtrans of diglycine from
      water to aqueous sucrose and, with AMBERff99SB/GLYCAM06, eliminate a caging
      effect seen in previous simulations of the protein ubiquitin with glucose.

PMID- 28437101
TI  - Ground State and Excited State Tuning in Ferric Dipyrrin Complexes Promoted by
      Ancillary Ligand Exchange.
AB  - Three ferric dipyrromethene complexes featuring different ancillary ligands were
      synthesized by one electron oxidation of ferrous precursors. Four-coordinate iron
      complexes of the type (ArL)FeX2 [ArL = 1,9-(2,4,6-Ph3C6H2)2-5
      mesityldipyrromethene] with X = Cl or tBuO were prepared and found to be high
      spin (S = 5/2), as determined by superconducting quantum interference device
      magnetometry, electron paramagnetic resonance, and 57Fe Mossbauer spectroscopy.
      The ancillary ligand substitution was found to affect both ground state and
      excited properties of the ferric complexes examined. While each ferric complex
      displays reversible reduction and oxidation events, each alkoxide for chloride
      substitution results in a nearly 600 mV cathodic shift of the FeIII/II couple.
      The oxidation event remains largely unaffected by the ancillary ligand
      substitution and is likely dipyrrin-centered. While the alkoxide substituted
      ferric species largely retain the color of their ferrous precursors,
      characteristic of dipyrrin-based ligand-to-ligand charge transfer (LLCT), the
      dichloride ferric complex loses the prominent dipyrrin chromophore, taking on a
      deep green color. Time-dependent density functional theory analyses indicate the
      weaker-field chloride ligands allow substantial configuration mixing of ligand-to
      metal charge transfer into the LLCT bands, giving rise to the color changes
      observed. Furthermore, the higher degree of covalency between the alkoxide ferric
      centers is manifest in the observed reactivity. Delocalization of spin density
      onto the tert-butoxide ligand in (ArL)FeCl(OtBu) is evidenced by hydrogen atom
      abstraction to yield (ArL)FeCl and HOtBu in the presence of substrates containing
      weak C-H bonds, whereas the chloride (ArL)FeCl2 analogue does not react under
      these conditions.

PMID- 28437102
TI  - Insights into the Complex Photophysics and Photochemistry of the Simplest
      Nitroaromatic Compound: A CASPT2//CASSCF Study on Nitrobenzene.
AB  - Nitrobenzene is the simplest nitroaromatic compound and yet is characterized by a
      challenging and rich photophysics and photochemistry. In the present
      contribution, the main decay paths undertaken by the system after UV absorption
      from both the brightest 1(Lapipi*) and the lowest 1(nApi*) singlet excited states
      have been characterized by means of CASPT2//CASSCF computations. The obtained
      results match with the main photophysical properties experimentally reported: the
      lack of fluorescence and phosphorescence emission is justified by the presence of
      accessible conical intersections and intersystem crossing regions between,
      respectively, the 1(nApi*) and 3(nApi*) states and the ground state, while the
      high triplet quantum yield is attributable to the strong coupling between the
      1(nApi*) and 3(piOpi*) states along the main decay path of the former. Two not
      previously reported singlet-triplet crossing regions, termed (T1/S0)stc-NO and
      (T1/S0)stc-ep, have been here documented, from which the ground state can decay
      toward NO and phenoxy radical production and toward the formation of an epoxide
      ring structure, respectively. A possible mechanism leading to the
      photoisomerization of the nitro into the nitrite group, believed to be a key step
      in the photodegradation of nitrobenzene, has been proposed, based on the
      geometrical deformation recorded along the decay path leading from the 1(nApi*)
      state back to the original ground state through a conical intersection
      characterized by a significant shortening of the carbon-nitrogen bond.

PMID- 28437104
TI  - Redox-Active Macrocycles for Organic Rechargeable Batteries.
AB  - Organic rechargeable batteries, composed of redox-active molecules, are emerging
      as candidates for the next generation of energy storage materials because of
      their large specific capacities, cost effectiveness, and the abundance of organic
      precursors, when compared with conventional lithium-ion batteries. Although redox
      active molecules often display multiple redox states, precise control of a
      molecule's redox potential, leading to a single output voltage in a battery,
      remains a fundamental challenge in this popular field of research. By combining
      macrocyclic chemistry with density functional theory calculations (DFT), we have
      identified a structural motif that more effectively delocalizes electrons during
      lithiation events in battery operations-namely, through-space electron
      delocalization in triangular macrocyclic molecules that exhibit a single well
      defined voltage profile-compared to the discrete multiple voltage plateaus
      observed for a homologous macrocyclic dimer and an acyclic derivative of
      pyromellitic diimide (PMDI). The triangular macrocycle, incorporating three PMDI
      units in close proximity to one another, exhibits a single output voltage at 2.33
      V, compared with two peaks at (i) 2.2 and 1.95-1.60 V for reduction and (ii) 1.60
      1.95 and 2.37 V for oxidation of the acyclic PMDI derivative. By investigating
      the two cyclic derivatives with different conformational dispositions of their
      PMDI units and the acyclic PMDI derivative, we identified noticeable changes in
      interactions between the PMDI units in the two cyclic derivatives under reducing
      conditions, as determined by differential pulse voltammetry, solution-state
      spectroelectrochemistry, and variable-temperature UV-Vis spectra. The numbers and
      relative geometries of the PMDI units are found to alter the voltage profile of
      the active materials significantly during galvanostatic measurements, resulting
      in a desirable single plateau for the triangular macrocycle. The present
      investigation reveals that understanding and controlling the relative
      conformational dispositions of redox-active units in macrocycles are key to
      achieving high energy density and long cycle-life electrodes for organic
      rechargeable batteries.

PMID- 28437103
TI  - Ion-Pair Oligomerization of Chromogenic Triangulenium Cations with Cyanostar
      Modified Anions That Controls Emission in Hierarchical Materials.
AB  - The hierarchical assembly of colored cationic molecules with receptor-modified
      counteranions can be used to control optical properties in materials. However,
      our knowledge of when the optical properties emerge in the hierarchical
      organization and the variety of cation-anion salts that are available to create
      these materials is limited. In this work, we extend the salts from small halides
      to large inorganic anions and determine how the structure coevolves with the
      emission properties using solution assemblies. We study the chromogenic
      trioxatriangulenium (TOTA+) cation and its coassembly with cyanostar (CS)
      macrocycles selected to modify tetrafluoroborate (BF4-) counteranions through
      formation of 2:1 sandwich complexes. In the solid state, the TOTA+ cation stacks
      in an alternating manner with the sandwich complexes producing new red-shifted
      emission and absorption bands. Critical to assigning the structural origin of the
      new optical features across the four levels of organization (1 degrees  -> 4
      degrees ) is the selection of specific solvents to produce and characterize
      different assemblies present in the hierarchical structure. A key species is the
      electrostatically stabilized ion pair between the TOTA+ cation and sandwich
      complex. The red-shifted features only emerge when the ion pairs oligomerize
      together into larger (TOTA.[CS2BF4])n assemblies. New electronic states emerge as
      a result of multiple copies of the TOTA+ making pi-contact with cyanostar-anion
      complexes. Our findings and the ease with which the materials can be prepared as
      crystals and films by mixing the salt with a receptor provide a strong platform
      for the de novo design of new optical materials.

PMID- 28437105
TI  - Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules
      with Haptics.
AB  - Haptic technology facilitates user interaction with the virtual world via the
      sense of touch. In molecular docking, haptics enables the user to sense the
      interaction forces during the docking process. Here we describe a haptics
      assisted interactive software tool, called Haptimol_RD, for the study of docking
      interactions. By utilizing GPU-accelerated proximity querying methods very large
      systems can now be studied. Methods for force scaling, multipoint collision
      response and haptic navigation are described that address force stability issues
      that are particular to the interactive docking of large systems. Thus,
      Haptimol_RD expands, for the first time, the use of interactive biomolecular
      haptics to the study of protein-protein interactions. Unlike existing approaches,
      Haptimol_RD is designed to run on relatively inexpensive consumer-level hardware
      and is freely available to the community.

PMID- 28437107
TI  - Multiple-State Nonadiabatic Dynamics Simulation of Photoisomerization of
      Acetylacetone with the Direct ab Initio QTMF Approach.
AB  - In the present work, the quantum trajectory mean-field (QTMF) approach is
      numerically implemented by ab initio calculation at the level of the complete
      active space self-consistent field, which is used to simulate photoisomerization
      of acetylacetone at ~265 nm. The simulated results shed light on the possible
      nonadiabatic pathways from the S2 state and mechanism of the photoisomerization.
      The in-plane proton transfer and the subsequent S2 -> S1 transition through the E
      S2/S1-1 intersection region is the predominant route to the S1 state. Meanwhile,
      rotational isomerization occurs in the S2 state, which is followed by internal
      conversion to the S1 state in the vicinity of the E-S2/S1-2 conical intersection.
      As a minor pathway, the direct S2 -> S1 -> S0 transition can take place via the E
      S2/S1/S0 three-state intersection region. The rotamerization in the S1 state was
      determined to be the key step for formation of nonchelated enolic isomers. The
      final formation yield is predicted to be 0.57 within the simulated period. The
      time constant for the S2 proton transfer was experimentally inferred to be ~70.0
      fs in the gas phase and ~50.0 fs in dioxane, acetonitrile, and n-hexane, which is
      well-reproduced by the present QTMF simulation. The S1 lifetime of 2.11 ps
      simulated here is in excellent agreement with the experimentally inferred values
      of 2.12, 2.13, and 2.25 ps in n-hexane, acetonitrile, and dioxane, respectively.
      The present study provides clear evidence that a direct ab initio QTMF approach
      is a reliable tool for simulating multiple-state nonadiabatic dynamics processes.

PMID- 28437106
TI  - Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by
      Fragment Screening.
AB  - Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair
      pathway and it is overexpressed in several cancers, representing an attractive
      target for the development of inhibitors. Despite the extensive efforts in
      targeting the ubiquitin system, very few E2 binders have currently been
      discovered. Herein we report the identification of a new allosteric pocket on
      Ube2T through a fragment screening using biophysical methods. Several fragments
      binding to this site inhibit ubiquitin conjugation in vitro.

PMID- 28437108
TI  - Design of a Toolbox of RNA Thermometers.
AB  - Biomolecular temperature sensors can be used for efficient control of large
      volume bioreactors, for spatiotemporal imaging and control of gene expression,
      and to engineer robustness to temperature in biomolecular circuit design.
      Although RNA-based sensors, called "thermometers", have been investigated in both
      natural and synthetic contexts, an important challenge is to design diverse
      responses to temperature differing in sensitivity and threshold. We address this
      issue by constructing a library of RNA thermometers based on thermodynamic
      computations and experimentally measuring their activities in cell-free
      biomolecular "breadboards". Using free energies of the minimum free energy
      structures as well as melt profile computations, we estimated that a diverse set
      of temperature responses were possible. We experimentally found a wide range of
      responses to temperature in the range 29-37  degrees C with fold-changes varying
      over 3-fold around the starting thermometer. The sensitivities of these responses
      ranged over 10-fold around the starting thermometer. We correlated these
      measurements with computational expectations, finding that although there was no
      strong correlation for the individual thermometers, overall trends of diversity,
      fold-changes, and sensitivities were similar. These results present a toolbox of
      RNA-based circuit elements with diverse temperature responses.

PMID- 28437109
TI  - Structure of the Fundamental Lipopeptide Surfactin at the Air/Water Interface
      Investigated by Sum Frequency Generation Spectroscopy.
AB  - The lipopeptide surfactin produced by certain strains of Bacillus subtilis is a
      powerful biosurfactant possessing potentially useful antimicrobial properties. In
      order to better understand its surface behavior, we have used surface sensitive
      sum frequency generation (SFG) vibrational spectroscopy in the C-H and C?O
      stretching regions to determine its structure at the air/water interface. Using
      surfactin with the leucine groups of the peptide ring perdeuterated, we have
      shown that a majority of the SFG signals arise from the 4 leucine residues. We
      find that surfactin forms a robust film, and that its structure is not affected
      by the number density at the interface or by pH variation of the subphase. The
      spectra show that the ring of the molecule lies in the plane of the surface
      rather than perpendicular to it, with the tail lying above this, also in the
      plane of the interface.

PMID- 28437110
TI  - Ultrafast Transient Absorption Spectroscopy of the Sunscreen Constituent
      Ethylhexyl Triazone.
AB  - The ultrafast photoprotection mechanisms in operation in ethylhexyl triazone
      (EHT, octyl triazone), an approved ultraviolet-B (UV-B) chemical filter for
      commercial sunscreens, remain elusive, with a notable absence of ultrafast time
      resolved measurements. These large organic molecules are of increasing interest
      as they are suspected to be less likely to penetrate the skin than some of the
      smaller approved filters, thereby reducing the possible adverse effects from
      sunscreen products. We apply femtosecond transient absorption spectroscopy with
      electronic structure calculations to unravel the complete photodeactivation
      mechanism that EHT undergoes after UV-B irradiation. We propose that this
      involves ultrafast internal conversion of the initially photoexcited n1pipi*
      state that couples to the ground state via a 11pipi*/S0 conical intersection,
      enabling multiple absorption and recovery cycles, as one would anticipate from a
      highly efficient filter. We also observe long-lived photoproducts which, based on
      previous studies along with present electronic structure calculations, we
      attribute to trapped excited populations in the S1 and T1 states.

PMID- 28437111
TI  - Mesostructure of Mesoporous Silica/Anodic Alumina Hierarchical Membranes Tuned
      with Ethanol.
AB  - Hierarchically structured membranes composed of mesoporous silica embedded inside
      the channels of anodic alumina (MS-AAM) were synthesized using the aspiration
      method. Ethanol is shown to have a significant effect on the type and
      organization of the mesoporous silica phase. Detailed textural analysis revealed
      that the pore size distribution of the mesoporous silica narrows and the degree
      of ordering increases with decreasing ethanol concentration used in the synthesis
      mixture. The silica mesopores were synthesized with pores as small as 6 nm in
      diameter, with the channel direction oriented in lamellar, circular, and columnar
      directions depending on the ethanol content. This study reveals ethanol
      concentration as a key factor behind the synthesis of an ordered mesoporous
      silica-anodic alumina membrane that can increase its functionality for membrane
      based applications.

PMID- 28437112
TI  - Visualization of Individual Images in Patterned Organic-Inorganic Multilayers
      Using GISAXS-CT.
AB  - Using grazing-incidence small-angle scattering (GISAXS) with computed tomography
      (CT), we have individually reconstructed the spatial distribution of a thin gold
      (Au) layer buried under a thin poly(styrene-b-2-vinylpyridine) (PS-b-P2VP) layer.
      Owing to the difference between total reflection angles of Au and PS-b-P2VP, the
      scattering profiles for Au nanoparticles and self-assembled nanostructures of PS
      b-P2VP could be independently obtained by changing the X-ray angle of incidence.
      Reconstruction of scattering profiles allows one to separately characterize
      spatial distributions in Au and PS-b-P2VP nanostructures.

PMID- 28437114
TI  - Nanoparticle Size Control in Microemulsion Synthesis.
AB  - Quasi-monodisperse populations of (H3O)Y3F10.xH2O nanocrystals of varying size
      are prepared in Igepal-stabilized microemulsions. Correlations between
      microemulsion composition, micelle hydrodynamic radius, and final nanoparticle
      size are established and shed light on the mechanism of particle size control.
      Under the conditions considered here, size control appears to be primarily
      governed by the number of micelles and the quantities of precursor ions. More
      specifically, the number of NPs formed can be successfully correlated with the
      number of micelles present and final NP size is, in turn, determined by the
      number of nuclei and the total amount of material available for nanocrystal
      formation. This insight into nanoparticle formation facilitates the selection of
      appropriate synthetic conditions for the preparation of populations of a targeted
      size.

PMID- 28437113
TI  - Development and Application of a Recyclable High-Load Magnetic Co/C Hybrid ROMP
      Derived Benzenesulfonyl Chloride Reagent and Utility of Corresponding Analogues.
AB  - The development and application of high-load, recyclable magnetic Co/C hybrid
      ROMP-derived benzenesulfonyl chloride and analogues is reported. The regeneration
      and utility of these reagents in the methylation/alkylation of various carboxylic
      acids is demonstrated via efficient retrieval of the magnetic reagent with a
      neodymium magnet. Additional reactions employing the analogue sulfonic acid and
      in situ generated magnetic benzenesulfonyl azide are also reported.

PMID- 28437115
TI  - Development and Implementation of Advanced Fitting Methods for the Calculation of
      Accurate Molecular Structures.
AB  - The determination of accurate equilibrium molecular structures plays a
      fundamental role for understanding many physical-chemical properties of
      molecules, ranging from the precise evaluation of the electronic structure to the
      analysis of dynamical and environmental effects in tuning their overall behavior.
      For this purpose the so-called semiexperimental approach, based on a nonlinear
      least-squares fit of the moments of inertia associated with a set of available
      isotopologues, allows one to obtain very accurate results, without the
      unfavorable computational cost characterizing high-level quantum chemical
      methods. In the present work the MSR (Molecular Structure Refinement) software
      for the determination of equilibrium structures by means of the semiexperimental
      approach is presented, and its implementation is discussed in some detail. The
      software, which is interfaced with a powerful graphical user interface, includes
      different optimization algorithms, an extended error analysis, and a number of
      advanced features, the most remarkable ones concerning the choice of internal
      coordinates and the method of predicate observations. In particular, a new black
      box scheme for defining automatically a suitable set of nonredundant internal
      coordinates of A1 symmetry in place of the customary Z-matrix has been designed
      and tested. Finally, the implementation of the method of the predicate
      observations is discussed and validated for a set of test molecules. As an
      original application, the method is employed for the determination of the
      semiexperimental structure for the most stable conformer of glycine.

PMID- 28437116
TI  - Pump-Power Dependence of Coherent Acoustic Phonon Frequencies in Colloidal
      CdSe/CdS Core/Shell Nanoplatelets.
AB  - Femtosecond optical pump-probe spectroscopy resolves hitherto unobserved coherent
      acoustic phonons in colloidal CdSe/CdS core/shell nanoplatelets (NPLs). With
      increasing pump fluence, the frequency of the in-plane acoustic mode increases
      from 5.2 to 10.7 cm-1, whereas the frequency of the out-of-plane mode remains at
      ~20 cm-1. Analysis of the oscillation phases suggests that the coherent acoustic
      phonon generation mechanism transitions from displacive excitation to
      subpicosecond Auger hole trapping with increasing pump fluence. The measurements
      yield Huang-Rhys parameters of ~10-2 for both acoustic modes. The weak electron
      phonon coupling strengths favor the application of NPLs in optoelectronics.

PMID- 28437117
TI  - Optimal Sensitizer Concentration in Single Upconversion Nanocrystals.
AB  - Each single upconversion nanocrystal (UCNC) usually contains thousands of photon
      sensitizers and hundreds of photon activators to up-convert near-infrared photons
      into visible and ultraviolet emissions. Though in principle further increasing
      the sensitizers' concentration will enhance the absorption efficiency to produce
      brighter nanocrystals, typically 20% of Yb3+ ions has been used to avoid the so
      called "concentration quenching" effect. Here we report that the concentration
      quenching effect does not limit the sensitizer concentration and NaYbF4 is the
      most bright host matrix. Surface quenching and the large size of NaYbF4
      nanocrystals are the only factors limiting this optimal concentration. Therefore,
      we further designed sandwich nanostructures of NaYbF4 between a small template
      core to allow an epitaxial growth of the size-tunable NaYbF4 shell enclosed by an
      inert shell to minimize surface quenching. As a result, the suspension containing
      25.2 nm sandwich structure UCNCs is 1.85 times brighter than the homogeneously
      doped ones, and the brightness of each single 25.2 nm heterogeneous UCNC is
      enhanced by nearly 3 times compared to the NaYF4: 20% Yb3+, 4% Tm3+ UCNCs in
      similar sizes. Particularly, the blue emission intensities of the UCNCs with the
      sandwich structure in the size of 13.6 and 25.2 nm are 1.36 times and 3.78 times
      higher than that of the monolithic UCNCs in the similar sizes. Maximizing the
      sensitizer concentration will accelerate the development of brighter and smaller
      UCNCs as more efficient biomolecule probes or photon energy converters.

PMID- 28437118
TI  - Blue Light Photocatalytic Glycosylation without Electrophilic Additives.
AB  - Photocatalytic formation of glycosidic bonds employing stable and readily
      accessible O-glycosyl derivatives of 2,2,6,6-tetramethylpiperidin-1-ol is
      presented that employs an iridium-based photocatalyst and blue LEDs. The reaction
      proceeds at room temperature and in the absence of additives other than 4 A
      molecular sieves. Stereoselectivities are modest but nevertheless dependent on
      the anomeric configuration of the donor, suggesting a substantial degree of
      concerted character.

PMID- 28437119
TI  - Synthesis of Naphthoquinolizinones through Rh(III)-Catalyzed Double C(sp2)-H Bond
      Carbenoid Insertion and Annulation of 2-Aryl-3-cyanopyridines with alpha-Diazo
      Carbonyl Compounds.
AB  - An unprecedented Rh(III)-catalyzed double C(sp2)-H bond carbenoid insertion and
      annulation of 2-aryl-3-cyanopyridines with alpha-diazo carbonyl compounds is
      presented. Through this cascade reaction, a series of naphthoquinolizinone
      derivatives with a large pi-system were efficiently prepared. The reactions could
      selectively afford naphthoquinolizinones with either an amine or an amide unit
      attached on the 11-position depending on the nature of the solvent and the
      additive used. Compared with literature methods, this is a more efficient,
      convenient, and atom-economic way to provide polycyclic heteroaromatic compounds
      through direct pi-extension of simple aromatics via inert C-H bond activation and
      functionalization.

PMID- 28437120
TI  - Mindfulness-oriented recovery enhancement for internet gaming disorder in U.S.
      adults: A stage I randomized controlled trial.
AB  - Empirical studies have identified increasing rates of Internet gaming disorder
      (IGD) and associated adverse consequences. However, very few evidence-based
      interventions have been evaluated for IGD or problematic video gaming behaviors.
      This study evaluated Mindfulness-Oriented Recovery Enhancement (MORE) as a
      treatment for IGD. Thirty adults (Mage = 25.0, SD = 5.4) with IGD or problematic
      video gaming behaviors were randomized to 8 weeks of group-based MORE or 8 weeks
      of a support group (SG) control condition. Outcome measures were administered at
      pre- and posttreatment and 3-months following treatment completion using self
      report instruments. Linear mixed models were used for outcome analyses. MORE
      participants had significantly greater reductions in the number of Diagnostic and
      Statistical Manual of Mental Disorders-5 IGD criteria they met, craving for video
      gaming, and maladaptive cognitions associated with gaming than SG participants,
      and therapeutic benefits were maintained at 3-month follow-up. MORE is a
      promising treatment approach for IGD. (PsycINFO Database Record

PMID- 28437121
TI  - Follow-up treatment effects of contingency management and motivational
      interviewing on substance use: A meta-analysis.
AB  - Motivation is an integral factor in substance use treatment and long-term
      recovery. However, it is unclear what role intrinsic and extrinsic motivation
      play across different treatment modalities. A meta-analysis (N = 84) was
      performed to estimate the pooled effect size of Motivational Interviewing (MI;
      primarily targeting intrinsic motivation) and contingency management (CM;
      primarily targeting extrinsic motivation) at different follow-up periods.
      Collapsed across all substance types, CM had a significant effect at 3-month
      follow-up, only. In contrast, MI had a significant effect at 6-month follow-up,
      only. CM had small and medium effects on multiple substances at 3-month follow-up
      (i.e., tobacco, marijuana, stimulants, polysubstances), but not at 6-month follow
      up. MI had 1 significant medium effect at 3-month follow-up (i.e., marijuana),
      but several significant small effects at 6-month follow-up (i.e., alcohol,
      tobacco, polysubstances). This meta-analysis suggests that both CM and MI promote
      reductions in a range of substances, even several months after the intervention
      concludes. Further, these results provide some evidence that extrinsically
      focused CM may produce medium follow-up effects in the short run, but
      intrinsically focused MI may produce small but durable follow-up effects.
      However, this interpretation is complicated by the differences between the MI and
      CM studies that preclude statistical tests comparing effect sizes, and few
      studies assessed motivation itself. Future researchers should investigate how
      motivational dynamics impact lasting outcomes in substance use treatment.
      (PsycINFO Database Record

PMID- 28437122
TI  - Childhood family characteristics and prescription drug misuse in a national
      sample of Latino adults.
AB  - Prescription drug misuse is a growing public health concern and has been
      understudied in Latino populations. The current study tests the relationships
      between childhood and family characteristics and prescriptions drug misuse among
      adult Latinos. A subsample of 8,308 Latinos from the National Epidemiologic
      Survey on Alcohol and Related Conditions (NESARC) were examined. Logistic
      regression analyses tested associations between parental alcoholism, parental
      divorce before age 18, and parental death before age 18 and prescription drug
      misuse and prescription drug use disorder. Parental alcoholism and parental
      divorce increased the odds of both prescription drug misuse and use disorder.
      Parental death increased the odds of prescription drug use disorders. The results
      have important implications for understanding the complex associations between
      family psychosocial history and prescription drug misuse. (PsycINFO Database
      Record

PMID- 28437123
TI  - Distress tolerance and physiological reactivity to stress predict women's
      problematic alcohol use.
AB  - Research has shown that measures of reactivity to distress-including distress
      tolerance and physiological reactivity to stress-are dysregulated in women who
      misuse alcohol. These variables may interact and create a risk profile for young
      adult women, reflecting patterns of stress reactivity that confer a risk for
      alcohol misuse. The current study tested this hypothesis by examining the
      independent and interactive associations of subjective distress tolerance,
      behavioral distress tolerance, and physiological stress reactivity with women's
      alcohol misuse. The study was conducted with a sample of 91 college women
      recruited on a large northeastern university campus. Results showed that
      subjective levels of distress tolerance and physiological reactivity to stress
      (skin conductance reactivity, SCR), but not behavioral distress tolerance, were
      independently associated with alcohol misuse. In addition, subjective distress
      tolerance moderated the relationship between SCR and negative alcohol-related
      consequences. Specifically, women with low physiological reactivity (SCR) to a
      stressful task and greater urge to quickly rid themselves of distress (low
      subjective distress tolerance) endorsed a significantly greater number of adverse
      consequences from their alcohol use. These results extend prior findings by
      showing that, even among a nonclinical sample of women, lower stress reactivity
      in combination with low subjective distress tolerance is associated with
      increased risk for various drinking-related negative consequences. (PsycINFO
      Database Record

PMID- 28437124
TI  - Marijuana and tobacco cigarettes: Estimating their behavioral economic
      relationship using purchasing tasks.
AB  - Although marijuana and tobacco are commonly coused, the nature of their
      relationship has not been fully elucidated. Behavioral economics has
      characterized the relationship between concurrently available commodities but has
      not been applied to marijuana and tobacco couse. U.S. adults >=18 years who
      coused marijuana and tobacco cigarettes were recruited via Mechanical Turk, a
      crowdsourcing service by Amazon. Participants (N = 82) completed online
      purchasing tasks assessing hypothetical marijuana or tobacco cigarette puff
      consumption across a range of per-puff prices; 2 single-commodity tasks assessed
      these when only 1 commodity was available, and 2 cross-commodity tasks assessed
      these in the presence of a concurrently available fixed-price commodity.
      Purchasing tasks generated measures of demand elasticity, that is, sensitivity of
      consumption to prices. In single-commodity tasks, consumption of tobacco
      cigarette puffs (elasticity of demand: alpha = 0.0075; 95% confidence interval
      [0.0066, 0.0085], R2 = 0.72) and of marijuana puffs (alpha = .0044; 95%
      confidence interval [0.0038, 0.0049], R2 = 0.71) declined significantly with
      increases in price per puff. In cross-commodity tasks when both tobacco cigarette
      puffs and marijuana puffs were available, demand for 1 commodity was independent
      of price increases in the other commodity (ps > .05). Results revealed that, in
      this small sample, marijuana and tobacco cigarettes did not substitute for each
      other and did not complement each other; instead, they were independent of each
      other. These preliminary results can inform future studies assessing the economic
      relationship between tobacco and marijuana in the quickly changing policy climate
      in the United States. (PsycINFO Database Record

PMID- 28437125
TI  - When and why is religious attendance associated with antigay bias and gay rights
      opposition? A justification-suppression model approach.
AB  - Even in relatively tolerant countries, antigay bias remains socially divisive,
      despite being widely viewed as violating social norms of tolerance. From a
      Justification-Suppression Model (JSM) framework, social norms may generally
      suppress antigay bias in tolerant countries, yet be "released" by religious
      justifications among those who resist gay rights progress. Across large,
      nationally representative US samples (Study 1) and international samples (Study
      2, representing a total of 97 different countries), over 215,000 participants,
      and various indicators of antigay bias (e.g., dislike, moral condemnation,
      opposing gay rights), individual differences in religious attendance was uniquely
      associated with greater antigay bias, over and above religious fundamentalism,
      political ideology, and religious denomination. Moreover, in 4 of 6 multilevel
      models, religious attendance was associated with antigay bias in countries with
      greater gay rights recognition, but was unrelated to antigay bias in countries
      with lower gay rights recognition (Study 2). In Study 3, Google searches for a
      religious justification ("love the sinner hate the sin") coincided temporally
      with gay-rights relevant searches. In U.S. (Study 4) and Canadian (Study 5)
      samples, much of the association between religious attendance and antigay bias
      was explained by "sinner-sin" religious justification, with religious attendance
      not associated with antigay bias when respondents reported relatively low
      familiarity with this justification (Study 5). These findings suggest that social
      divisions on homosexuality in relatively tolerant social contexts may be in large
      part due to religious justifications for antigay bias (consistent with the JSM),
      with important implications for decreasing bias. (PsycINFO Database Record

PMID- 28437126
TI  - How winning changes motivation in multiphase competitions.
AB  - What drives motivation in multiphase competitions? Adopting a dynamic approach,
      this research examines how temporary standing-being ahead of (vs. behind) one's
      opponent-in a multiphase competition shapes subsequent motivation. Six
      competitions conducted in the lab and in the field demonstrate that the impact of
      being ahead on contestants' motivation depends on when (i.e., in which phase of
      the competition) contestants learn they are in the lead. In the early phase,
      contestants are concerned about whether they can win; being ahead increases
      motivation by making winning seem more attainable. In the later phase, however,
      contestants are instead driven by how much additional effort they believe they
      need to invest; being ahead decreases motivation by reducing contestants'
      estimate of the remaining effort needed to win. Temporary standing thus has
      divergent effects on motivation in multiphase competitions, driven by a shift in
      contestants' main concern from the early to the later phase and thus the meaning
      they derive from being ahead of their opponent. By leveraging insights gained
      from approaching individuals' self-regulation as a dynamic process, this research
      advances understanding of how motivation evolves in a unique interdependent self
      regulatory context. (PsycINFO Database Record

PMID- 28437127
TI  - Building a Lego wall: Sequential action selection.
AB  - The present study draws together two distinct lines of enquiry into the selection
      and control of sequential action: motor sequence production and action selection
      in everyday tasks. Participants were asked to build 2 different Lego walls. The
      walls were designed to have hierarchical structures with shared and dissociated
      colors and spatial components. Participants built 1 wall at a time, under low and
      high load cognitive states. Selection times for correctly completed trials were
      measured using 3-dimensional motion tracking. The paradigm enabled precise
      measurement of the timing of actions, while using real objects to create an end
      product. The experiment demonstrated that action selection was slowed at decision
      boundary points, relative to boundaries where no between-wall decision was
      required. Decision points also affected selection time prior to the actual
      selection window. Dual-task conditions increased selection errors. Errors mostly
      occurred at boundaries between chunks and especially when these required
      decisions. The data support hierarchical control of sequenced behavior. (PsycINFO
      Database Record

PMID- 28437128
TI  - Neural dynamics of grouping and segmentation explain properties of visual
      crowding.
AB  - Investigations of visual crowding, where a target is difficult to identify
      because of flanking elements, has largely used a theoretical perspective based on
      local interactions where flanking elements pool with or substitute for properties
      of the target. This successful theoretical approach has motivated a wide variety
      of empirical investigations to identify mechanisms that cause crowding, and it
      has suggested practical applications to mitigate crowding effects. However, this
      theoretical approach has been unable to account for a parallel set of findings
      that crowding is influenced by long-range perceptual grouping effects. When the
      target and flankers are perceived as part of separate visual groups, crowding
      tends to be quite weak. Here, we describe how theoretical mechanisms for grouping
      and segmentation in cortical neural circuits can account for a wide variety of
      these long-range grouping effects. Building on previous work, we explain how
      crowding occurs in the model and explain how grouping in the model involves
      connected boundary signals that represent a key aspect of visual information. We
      then introduce new circuits that allow nonspecific top-down selection signals to
      flow along connected boundaries or within a surface contained by boundaries and
      thereby induce a segmentation that can separate the visual information
      corresponding to the flankers from the visual information corresponding to the
      target. When such segmentation occurs, crowding is shown to be weak. We compare
      the model's behavior to 5 sets of experimental findings on visual crowding and
      show that the model does a good job explaining the key empirical findings.
      (PsycINFO Database Record

PMID- 28437129
TI  - Acute Ankle Sprain in a Mouse Model: Changes in Knee-Joint Space.
AB  - CONTEXT:   Ankle sprains remain the most common orthopaedic injury. Conducting
      long-term studies in humans is difficult and costly, so the long-term
      consequences of an ankle sprain are not entirely known. OBJECTIVE:   To measure
      knee-joint space after a single surgically induced ankle sprain in mice. DESIGN: 
      Randomized controlled trial. SETTING:   University research laboratory. PATIENTS
      OR OTHER PARTICIPANTS:   Thirty male mice (CBA/2J) were randomly placed into 1 of
      3 surgical groups: the transected calcaneofibular ligament (CFL) group, the
      transected anterior talofibular ligament/CFL group, or a sham treatment group.
      The right ankle was operated on in all mice. MAIN OUTCOME MEASURE(S):   Three
      days after surgery, all of the mice were individually housed in cages containing
      a solid-surface running wheel, and daily running-wheel measurements were
      recorded. Before surgery and every 6 weeks after surgery, a diagnostic ultrasound
      was used to measure medial and lateral knee-joint space in both hind limbs.
      RESULTS:   Right medial (P = .003), right lateral (P = .002), left medial (P =
      .03), and left lateral (P = .002) knee-joint spaces decreased across the life
      span. The mice in the anterior talofibular ligament/CFL group had decreased right
      medial (P = .004) joint space compared with the sham and CFL groups starting at
      24 weeks of age and continuing throughout the life span. No differences occurred
      in contralateral knee-joint degeneration among any of the groups. CONCLUSIONS:  
      Based on current data, mice that sustained a surgically induced severe ankle
      sprain developed greater joint degeneration in the ipsilateral knee. Knee
      degeneration could result from accommodation to the laxity of the ankle or
      biomechanical alterations secondary to ankle instability. A single surgically
      induced ankle sprain could significantly affect knee-joint function.

PMID- 28437130
TI  - Lower Limb and Trunk Biomechanics After Fatigue in Competitive Female Irish
      Dancers.
AB  - CONTEXT:   Because of the increasing popularity of participation in Irish dance,
      the incidence of lower limb injuries is high among this competitive population.
      OBJECTIVE:   To investigate the effects of fatigue on the peak lower limb and
      trunk angles as well as the peak lower limb joint forces and moments of
      competitive female Irish dancers during the performance of a dance-specific
      single-limb landing. DESIGN:   Cross-sectional study. SETTING:   Laboratory.
      PATIENTS OR OTHER PARTICIPANTS:   Fourteen healthy, female, competitive Irish
      dancers (age = 19.4 +/- 3.7 years, height = 165.3 +/- 5.9 cm, mass = 57.9 +/- 8.2
      kg). INTERVENTION(S):   Participants performed an Irish dance-specific leap
      before and after a dance-specific fatigue protocol. During each landing movement,
      3-dimensional lower limb kinematics (250 Hz) and ground reaction forces (1000 Hz)
      were collected. Paired t tests were performed to determine the differences (P <=
      .05) in lower limb and trunk biomechanics prefatigue and postfatigue. MAIN
      OUTCOME MEASURE(S):   Peak lower limb and trunk angles as well as peak lower limb
      joint reaction forces and external moments. RESULTS:   Compared with the
      prefatigue trials, dancers landed with reduced ankle plantar flexion (P = .003)
      and hip external rotation (P = .007) and increased hip-adduction alignment (P =
      .034) postfatigue. Dancers displayed greater anterior shear (P = .003) and
      compressive (P = .024) forces at the ankle and greater external knee-flexion
      moments (P = .024) during the postfatigue compared with the prefatigue landing
      trials. CONCLUSIONS:   When fatigued, dancers displayed a decline in landing
      performance in terms of aesthetics as well as increased ankle- and knee-joint
      loading, potentially exposing them to a greater risk of injuries.

PMID- 28437131
TI  - Re-Irradiation Therapy for Locally Recurrent Head and Neck Cancer: A National
      Survey of Practice Patterns.
AB  - Using a customized survey consisting of two de-identified clinical scenarios with
      a total of 86 questions, we showed that substantial variability exists regarding
      recommendations for therapy of recurrent head and neck cancer. For inoperable
      gross recurrence arising in a previously irradiated field, recommendations were
      re-irradiation with curative intent (73%), re-irradiation with palliative intent
      (4%), chemotherapy alone (5%), and referral to tertiary center (18%). After
      salvage surgery, only 33% recommended adjuvant re-irradiation, with the remainder
      preferring observation (46%), chemotherapy alone (10%), and referral to tertiary
      center (11%). Significant differences were observed with respect to dose,
      fractionation, technique, and systemic therapy recommendations.

PMID- 28437132
TI  - Home Enteral Nutrition: Updates, Trends, and Challenges.
AB  - The true prevalence of home enteral nutrition (HEN) utilization is unclear and
      requires further study. HEN therapy has remained virtually unchanged for several
      decades. However, new trends in HEN are evolving; enteral nutrition is undergoing
      changes ranging from enteral feeding devices, ingredients used, practice
      innovations, and challenges with reimbursement. A 2006 Joint Commission call to
      action that reported 2 sentinel events related to misconnections set things into
      motion for the transition of enteral device connectors to become specific for
      enteral nutrition use, which will affect patients who receive HEN. Nutrition
      support clinicians are realizing that people fed enterally may also enjoy
      incorporating blended foods into their diets and may benefit from different
      nutrients and components (ie, phytonutrients, fiber, and prebiotics) present in
      natural foods, thereby resulting in the renaissance of food-based blenderized
      tube feedings. This article reviews HEN therapy data or the lack thereof, current
      practices, risks and benefits, future trends, and challenges with access devices,
      enteral feedings, and reimbursement. It also highlights areas where more research
      is needed, and it urges clinicians to get involved in legislative action or
      committees to facilitate improved processes and reimbursement for HEN.

PMID- 28437133
TI  - The impact of the centrifuge characteristics and centrifugation protocols on the
      cells, growth factors, and fibrin architecture of a leukocyte- and platelet-rich
      fibrin (L-PRF) clot and membrane.
AB  - L-PRF (leukocyte- and platelet-rich fibrin) is one of the four families of
      platelet concentrates for surgical use and is widely used in oral and
      maxillofacial regenerative therapies. The first objective of this article was to
      evaluate the mechanical vibrations appearing during centrifugation in four models
      of commercially available table-top centrifuges used to produce L-PRF and the
      impact of the centrifuge characteristics on the cell and fibrin architecture of a
      L-PRF clot and membrane. The second objective of this article was to evaluate how
      changing some parameters of the L-PRF protocol may influence its biological
      signature, independently from the characteristics of the centrifuge. In the first
      part, four different commercially available centrifuges were used to produce L
      PRF, following the original L-PRF production method (glass-coated plastic tubes,
      400 g force, 12 minutes). The tested systems were the original L-PRF centrifuge
      (Intra-Spin, Intra-Lock, the only CE and FDA cleared system for the preparation
      of L-PRF) and three other laboratory centrifuges (not CE/FDA cleared for L-PRF):
      A-PRF 12 (Advanced PRF, Process), LW-UPD8 (LW Scientific) and Salvin 1310 (Salvin
      Dental). Each centrifuge was opened for inspection, two accelerometers were
      installed (one radial, one vertical), and data were collected with a spectrum
      analyzer in two configurations (full-load or half load). All clots and membranes
      were collected into a sterile surgical box (Xpression kit, Intra-Lock). The exact
      macroscopic (weights, sizes) and microscopic (photonic and scanning electron
      microscopy SEM) characteristics of the L-PRF produced with these four different
      machines were evaluated. In the second part, venous blood was taken in two
      groups, respectively, Intra-Spin 9 ml glass-coated plastic tubes (Intra-Lock) and
      A-PRF 10 ml glass tubes (Process). Tubes were immediately centrifuged at 2700 rpm
      (around 400 g) during 12 minutes to produce L-PRF or at 1500 rpm during 14
      minutes to produce A-PRF. All centrifugations were done using the original L-PRF
      centrifuge (Intra-Spin), as recommended by the two manufacturers. Half of the
      membranes were placed individually in culture media and transferred in a new tube
      at seven experimental times (up to 7 days). The releases of transforming growth
      factor beta-1 (TGFbeta-1), platelet derived growth factor AB (PDGF-AB), vascular
      endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) were
      quantified using ELISA kits at these seven experimental times. The remaining
      membranes were used to evaluate the initial quantity of growth factors of the L
      PRF and A-PRF membranes, through forcible extraction. Very significant
      differences in the level of vibrations at each rotational speed were observed
      between the four tested centrifuges. The original L-PRF centrifuge (Intra-Spin)
      was by far the most stable machine in all configurations and always remained
      under the threshold of resonance, unlike the three other tested machines. At the
      classical speed of production of L-PRF, the level of undesirable vibrations on
      the original centrifuge was between 4.5 and 6 times lower than with other
      centrifuges. Intra-Spin showed the lowest temperature of the tubes. A-PRF and
      Salvin were both associated with a significant increase in temperature in the
      tube. Intra-Spin produced the heaviest clot and quantity of exudate among the
      four techniques. A-PRF and LW produced much lighter, shorter and narrower clots
      and membranes than the two other centrifuges. Light microscopy analysis showed
      relatively similar features for all L-PRF types (concentration of cell bodies in
      the first half). However, SEM illustrated considerable differences between
      samples. The original Intra-Spin L-PRF showed a strongly polymerized thick fibrin
      matrix and all cells appeared alive with a normal shape, including the textured
      surface aspect of activated lymphocytes. The A-PRF, Salvin and LW PRF-like
      membranes presented a lightly polymerized slim fibrin gel and most of the visible
      cell bodies appeared destroyed (squashed or shrunk). In the second part of this
      study, the slow release of the three tested growth factors from original L-PRF
      membranes was significantly stronger (more than twice stronger, p<0.001) at all
      experimental times than the release from A-PRF membranes. No trace of BMP2 could
      be detected in the A-PRF. A slow release of BMP2 was detected during at least 7
      days in the original L-PRF. Moreover, the original L-PRF clots and membranes
      (produced with 9 mL blood) were always significantly larger than the A-PRF
      (produced with 10 mL blood). The A-PRF membranes dissolved in vitro after less
      than 3 days, while the L-PRF membrane remained in good shape during at least 7
      days. Each centrifuge has its clear own profile of vibrations depending on the
      rotational speed, and the centrifuge characteristics are directly impacting the
      architecture and cell content of a L-PRF clot. This result may reveal a
      considerable flaw in all the PRP/PRF literature, as this parameter was never
      considered. The original L-PRF clot (Intra-Spin) presented very specific
      characteristics, which appeared distorted when using centrifuges with a higher
      vibration level. A-PRF, LW and Salvin centrifuges produced PRF-like materials
      with a damaged and almost destroyed cell population through the standard
      protocol, and it is therefore impossible to classify these products in the L-PRF
      family. Moreover, when using the same centrifuge, the original L-PRF protocol
      allowed producing larger clots/membranes and a more intense release of growth
      factors (biological signature at least twice stronger) than the modified A-PRF
      protocol. Both protocols are therefore significantly different, and the clinical
      and experimental results from the original L-PRF shall not be extrapolated to the
      A-PRF. Finally, the comparison between the total released amounts and the initial
      content of the membrane (after forcible extraction) highlighted that the
      leukocytes living in the fibrin matrix are involved in the production of
      significant amounts of growth factors. The centrifuge characteristics and
      centrifugation protocols impact significantly and dramatically the cells, growth
      factors and fibrin architecture of L-PRF.

PMID- 28437134
TI  - The psychometric properties of the Iranian version of revised prenatal coping
      inventory (Nu PCI) in healthy pregnant women: a confirmatory factor analysis.
AB  - The Revised Prenatal Coping Inventory (Nu PCI) is a self-report instrument that
      focuses on the coping styles of pregnant women during the prenatal period. The
      present study aimed to translate the scale and evaluate the psychometric
      properties of the Iranian version of the Nu PCI in healthy pregnant women.
      Beaton's recommendations have been used for the translation and cultural
      adaptation of this scale. Reliability, content, and face validity were performed
      to assess the psychometric properties of the scale. The results indicated that
      the Nu PCI was successfully translated into the Persian language, with both the
      total scale and subscales exhibiting both content validity and internal
      consistency. Confirmatory factor analyses revealed that the conceptual three
      factor structure of the measure had good fit indices. Reliability was evaluated
      using internal consistency. Cronbach Alpha coefficient was 0.92 and intra-class
      correlation coefficient (ICC) was 0.91. Therefore, the Nu PCI is a reliable
      instrument to measure prenatal coping patterns in primigravida healthy pregnant
      women.

PMID- 28437135
TI  - D3GB: An Interactive Genome Browser for R, Python, and WordPress.
AB  - Genome browsers are useful not only for showing final results but also for
      improving analysis protocols, testing data quality, and generating result drafts.
      Its integration in analysis pipelines allows the optimization of parameters,
      which leads to better results. New developments that facilitate the creation and
      utilization of genome browsers could contribute to improving analysis results and
      supporting the quick visualization of genomic data. D3 Genome Browser is an
      interactive genome browser that can be easily integrated in analysis protocols
      and shared on the Web. It is distributed as an R package, a Python module, and a
      WordPress plugin to facilitate its integration in pipelines and the utilization
      of platform capabilities. It is compatible with popular data formats such as
      GenBank, GFF, BED, FASTA, and VCF, and enables the exploration of genomic data
      with a Web browser.

PMID- 28437136
TI  - Enumeration of Ancestral Configurations for Matching Gene Trees and Species
      Trees.
AB  - Given a gene tree and a species tree, ancestral configurations represent the
      combinatorially distinct sets of gene lineages that can reach a given node of the
      species tree. They have been introduced as a data structure for use in the
      recursive computation of the conditional probability under the multispecies
      coalescent model of a gene tree topology given a species tree, the cost of this
      computation being affected by the number of ancestral configurations of the gene
      tree in the species tree. For matching gene trees and species trees, we obtain
      enumerative results on ancestral configurations. We study ancestral
      configurations in balanced and unbalanced families of trees determined by a given
      seed tree, showing that for seed trees with more than one taxon, the number of
      ancestral configurations increases for both families exponentially in the number
      of taxa n. For fixed n, the maximal number of ancestral configurations tabulated
      at the species tree root node and the largest number of labeled histories
      possible for a labeled topology occur for trees with precisely the same unlabeled
      shape. For ancestral configurations at the root, the maximum increases with
      [Formula: see text], where [Formula: see text] is a quadratic recurrence
      constant. Under a uniform distribution over the set of labeled trees of given
      size, the mean number of root ancestral configurations grows with [Formula: see
      text] and the variance with ~[Formula: see text]. The results provide a
      contribution to the combinatorial study of gene trees and species trees.

PMID- 28437137
TI  - Differential Requirement of the Ribosomal Protein S6 and Ribosomal Protein S6
      Kinase for Plant-Virus Accumulation and Interaction of S6 Kinase with Potyviral
      VPg.
AB  - Ribosomal protein S6 (RPS6) is an indispensable plant protein regulated, in part,
      by ribosomal protein S6 kinase (S6K) which, in turn, is a key regulator of plant
      responses to stresses and developmental cues. Increased expression of RPS6 was
      detected in Nicotiana benthamiana during infection by diverse plant viruses.
      Silencing of the RPS6 and S6K genes in N. benthamiana affected accumulation of
      Cucumber mosaic virus, Turnip mosaic virus (TuMV), and Potato virus A (PVA) in
      contrast to Turnip crinkle virus and Tobacco mosaic virus. In addition, the viral
      genome-linked protein (VPg) of TuMV and PVA interacted with S6K in plant cells,
      as detected by bimolecular fluorescence complementation assay. The VPg-S6K
      interaction was detected in cytoplasm, nucleus, and nucleolus, whereas the green
      fluorescent protein-tagged S6K alone showed cytoplasmic localization only. These
      results demonstrate that the requirement for RPS6 and S6K differs for diverse
      plant viruses with different translation initiation strategies and suggest that
      potyviral VPg-S6K interaction may affect S6K functions in both the cytoplasm and
      the nucleus.

PMID- 28437138
TI  - Epidemiology of Basil Downy Mildew.
AB  - Basil downy mildew (BDM) caused by the oomycete Peronospora belbahrii is a
      destructive disease of sweet basil (Ocimum basilicum) worldwide. It originated in
      Uganda in the 1930s and recently spread to Europe, the Middle East, Americas, and
      the Far East. Seed transmission may be responsible for its quick global spread.
      The pathogen attacks leaf blades, producing chlorotic lesions with ample dark
      asexual spores on the lower leaf surface. Oospores may form in the mesophyll of
      infected leaves. The asexual spores germinate on a wet leaf surface within 2 h
      and penetrate into the epidermis within 4 h. Spore germination and infection
      occur at a wide range of temperatures from 5 to 28.5 degrees C. Infection
      intensity depends on the length of dew period, leaf temperature, and inoculum
      dose. The duration of latent period (from infection to sporulation) extends from
      5 to 10 days, depending on temperature and light regime. The shortest is 5 days
      at 25 degrees C under continuous light. Sporulation requires high humidity but
      not free leaf wetness. Sporulation occurs at 10 to 26 degrees C. At the optimum
      temperature of 18 degrees C, the process of sporulation requires 7.5 h at
      relative humidity >= 85%, with 3 h for sporophores emergence from stomata and 4.5
      h for spore formation. Sporophores can emerge under light or darkness, but spore
      formation occurs in the dark only. Limited data are available on spore dispersal.
      Spores dispersed from sporulating plants contaminate healthy plants within 2 h of
      exposure. Settled spores may survive on leaf surface of healthy plants for
      prolonged periods, depending on temperature. Seed transmission of the disease
      occurs in Europe, but not in Israel or the United States. P. belbahrii in Israel
      also attacks species belonging to Rosemarinus, Nepeta, Agastache, Micromeria, and
      Salvia but not Plectranthus (coleus). A Peronospora species that infects coleus
      does not infect sweet basil. Control of BDM includes chemical, physical, and
      genetic means. The fungicide mefenoxam was highly effective in controlling the
      disease but resistant populations were quickly selected for in Israel and Europe
      rendering it ineffective. A new compound oxathiapiprolin (OSBP inhibitor) is
      highly effective. Nocturnal illumination of basil crops controls the disease by
      preventing sporulation. Daytime solar heating suppressed the disease effectively
      by reducing spore and mycelium viability. The most effective physical means is
      fanning. Nocturnal fanning prevents or limits dew deposition on leaf surfaces,
      and as a result, infection and sporulation diminish and epidemics are prevented.
      Genetic resistance occurs in wild basil and its transfer to sweet basil is under
      way.

PMID- 28437139
TI  - Protection Against Common Bean Rust Conferred by a Gene-Silencing Method.
AB  - Rust disease of the dry bean plant, Phaseolus vulgaris, is caused by the fungus
      Uromyces appendiculatus. The fungus acquires its nutrients and energy from bean
      leaves using a specialized cell structure, the haustorium, through which it
      secretes effector proteins that contribute to pathogenicity by defeating the
      plant immune system. Candidate effectors have been identified by DNA sequencing
      and motif analysis, and some candidates have been observed in infected leaves by
      mass spectrometry. To assess their roles in pathogenicity, we have inserted small
      fragments of genes for five candidates into Bean pod mottle virus. Plants were
      infected with recombinant virus and then challenged with U. appendiculatus. Virus
      infected plants expressing gene fragments for four of five candidate effectors
      accumulated lower amounts of rust and had dramatically less rust disease. By
      contrast, controls that included a fungal gene fragment for a septin protein not
      expressed in the haustorium died from a synergistic reaction between the virus
      and the fungus. The results imply that RNA generated in the plant moved across
      the fungal haustorium to silence effector genes important to fungal
      pathogenicity. This study shows that four bean rust fungal genes encode
      pathogenicity determinants and that the expression of fungal RNA in the plant can
      be an effective method for protecting bean plants from rust.

PMID- 28437140
TI  - A proven alternative to compression bandaging.

PMID- 28437142
TI  - Open-Label Trial of Vitamin D3 Supplementation in Children with Autism Spectrum
      Disorder.

PMID- 28437143
TI  - Motivations for Botanical Use by Socioeconomically Diverse, Urban Adults: Does
      Evidence Support Motivation?
AB  - OBJECTIVE: The study objectives were to characterize botanical dietary supplement
      (BDS) use and to compare the motivations for botanical supplement (BS) use to the
      efficacy of the botanical in a socioeconomically and racially diverse urban adult
      population. METHODS: Subjects were from the Healthy Aging in Neighborhoods of
      Diversity across the Life Span (HANDLS) study, a 20-year prospective health
      disparities study with African American and white adults from Baltimore,
      Maryland. All study participants completed two dietary recalls and a dietary
      supplement (DS) questionnaire in Wave 3 (n = 2140). Diet quality was evaluated by
      the Healthy Eating Index-2010 and the Mean Adequacy Ratio for 17 micronutrients.
      A comparison of reported motivations to efficacy reported in the literature of
      single BS was conducted. RESULTS: Approximately 50% (1062/2140) of participants
      took DS. Of these, 8% (n = 178) reported taking either BS or BDS. It was found
      that BDS users had better diet quality than DS users as well as nonusers of DS.
      The top three motivations for BDS users were to improve overall health, to
      maintain health, and to supplement the diet. There is limited evidence for the
      efficacy of most BS. Review of the efficacy of the 15 BS reported by >=5% of the
      study population revealed beneficial health roles for only fiber, gingko biloba
      extract EGb 761, and hawthorn berry. CONCLUSION: To the authors' knowledge, this
      study is the first to report a better quality diet with BDS use for a racially
      diverse urban population. Yet, improvement in diet is needed because overall
      quality did not achieve current recommendations. To improve overall health, it
      may be beneficial for this population to focus on dietary modifications to reduce
      the risks associated with chronic diseases. In general, the reported motivations
      for BS use were not supported by clinical evidence.

PMID- 28437144
TI  - Framingham Risk Score and Estimated 10-Year Cardiovascular Disease Risk Reduction
      by a Short-Term Yoga-Based LifeStyle Intervention.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of a short-term
      yoga-based lifestyle intervention program in lowering Framingham Risk Score (FRS)
      and estimated 10-year cardiovascular risk. METHODS: This was a single-arm, pre
      post interventional study including data from a historical cohort with low to
      moderate risk for cardiovascular disease (CVD). It was conducted in a tertiary
      care hospital. Participants with low (0 or 1 CVD risk factors) to moderately high
      risk (10-year risk between 10% and 20% and two or more CVD risk factors) were
      included. Participants with previously diagnosed CVD, defined as a history of
      myocardial infarction, congestive heart failure, or cerebrovascular accident,
      were excluded from the analysis. However, those with controlled hypertension were
      included. Intervention included a pretested short-term yoga-based lifestyle
      intervention, which included asanas (physical postures), pranayama (breathing
      exercises), meditation, relaxation techniques, stress management, group support,
      nutrition awareness program, and individualized advice. The intervention was for
      10 days, spread over 2 weeks. However, participants were encouraged to include it
      in their day-to-day life. Outcomes included changes in FRS, and estimated 10-year
      CVD risk from baseline to week 2. A gender-based subgroup analysis was also done,
      and correlation between changes in FRS and cardiovascular risk factors was
      evaluated. RESULTS: Data for 554 subjects were screened, and 386 subjects (252
      females) were included in the analysis. There was a significant reduction in FRS
      (p < 0.001) and estimated 10-year cardiovascular risk (p < 0.001) following the
      short-term yoga-based intervention. There was a strong positive correlation
      between reduction in FRS and serum total cholesterol (r = 0.60; p < 0.001). There
      was a moderate positive correlation between reduction in FRS and low-density
      lipoprotein cholesterol (r = 0.58; p < 0.001), and a weak but positive
      correlation between reduction in FRS and triglycerides (r = 0.26; p <= 0.001),
      serum very-low-density lipoprotein cholesterol (r = 0.29; p < 0.001), and
      systolic blood pressure (r = 0.20; p <= 0.001). CONCLUSIONS: This yoga-based
      lifestyle intervention program significantly reduced the CVD risk, as shown by
      lowered FRS and estimated 10-year CVD risk. Further testing of this promising
      intervention is warranted in the long term.

PMID- 28437145
TI  - The Effect of Yoga on Menstrual Disorders: A Systematic Review.
AB  - OBJECTIVE: To summarize and evaluate evidence for the effect of yoga on menstrual
      disorders. METHODS: PubMed, CINAHL/MEDLINE, Web of Science, AMED, and Scopus were
      searched for English-language literature relevant to the review question. All
      primary research studies were included. RESULTS: Fifteen studies described in 18
      papers were included in the review. A range of yoga interventions were used. Some
      studies used a combination of Asana, Pranayama, and other yogic relaxation or
      meditation techniques. All included studies reported some change in their outcome
      measures, suggesting reduced symptoms of menstrual distress following a yoga
      intervention; however, the heterogeneity and intensity of the interventions and
      outcome measures meant that findings have limited generalizability and
      applicability in practice settings. CONCLUSIONS: Further research on the
      relationship between yoga practice and menstrual disorders is warranted, but
      there must be both consistency in the methods, measures, and quality of studies
      and a shift toward research on yoga practices that are replicable outside of the
      clinical trial setting.

PMID- 28437146
TI  - Homeopathy for Allergic Rhinitis: A Systematic Review.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and effectiveness
      of homeopathic intervention in the treatment of seasonal or perennial allergic
      rhinitis (AR). METHOD: Randomized controlled trials evaluating all forms of
      homeopathic treatment for AR were included in a systematic review (SR) of studies
      published up to and including December 2015. Two authors independently screened
      potential studies, extracted data, and assessed risk of bias. Primary outcomes
      included symptom improvement and total quality-of-life score. Treatment effect
      size was quantified as mean difference (continuous data), or by risk ratio (RR)
      and odds ratio (dichotomous data), with 95% confidence intervals (CI). Meta
      analysis was performed after assessing heterogeneity and risk of bias. RESULTS:
      Eleven studies were eligible for SR. All trials were placebo-controlled except
      one. Six trials used the treatment approach known as isopathy, but they were
      unsuitable for meta-analysis due to problems of heterogeneity and data
      extraction. The overall standard of methods and reporting was poor: 8/11 trials
      were assessed as "high risk of bias"; only one trial, on isopathy for seasonal
      AR, possessed reliable evidence. Three trials of variable quality (all using
      Galphimia glauca for seasonal AR) were included in the meta-analysis: nasal
      symptom relief at 2 and 4 weeks (RR = 1.48 [95% CI 1.24-1.77] and 1.27 [95% CI
      1.10-1.46], respectively) favored homeopathy compared with placebo; ocular
      symptom relief at 2 and 4 weeks also favored homeopathy (RR = 1.55 [95% CI 1.33
      1.80] and 1.37 [95% CI 1.21-1.56], respectively). The single trial with reliable
      evidence had a small positive treatment effect without statistical significance.
      A homeopathic and a conventional nasal spray produced equivalent improvements in
      nasal and ocular symptoms. CONCLUSIONS: The low or uncertain overall quality of
      the evidence warrants caution in drawing firm conclusions about intervention
      effects. Use of either Galphimia glauca or a homeopathic nasal spray may have
      small beneficial effects on the nasal and ocular symptoms of AR. The efficacy of
      isopathic treatment of AR is unclear.

PMID- 28437147
TI  - Comparison of Two Types of Meditation on Patients' Psychosocial Responses During
      Radiation Therapy for Head and Neck Cancer.
AB  - OBJECTIVES: Radiation treatment for head and neck cancer introduces adaptive
      demands and subjects patients to significant and unique psychosocial challenges.
      There is growing evidence that meditation is useful in lessening anxiety and
      depression in cancer patients. This study compared the effects of two types of
      meditation training on the psychological responses of patients with head and neck
      cancer during radiation therapy. DESIGN: Randomized clinical trial. SETTING:
      Smilow Cancer Hospital at Yale New Haven. PATIENTS: A total of 29 patients with
      head and neck cancers were recruited and 28 patients were followed during their
      radiation therapy over 12 weeks. INTERVENTIONS: Depending on their group
      assignment, patients were taught one of two standardized meditations: meditation
      with a coach or self-meditation with a CD. OUTCOME MEASURES: Patient psychosocial
      responses were defined as anxiety, depression, and emotional distress and were
      measured by the Hospital and Anxiety Depression Scale (HADS) and the Emotional
      Distress Thermometer. Measures were self-reported and collected by the nurse
      manager at baseline and 6 and 12 weeks during the patient's scheduled weekly
      visit. RESULTS: No significant mean differences were found between the two
      meditation groups on all three outcomes: anxiety, depression, and emotional
      distress. Patients in both the meditation with a coach and self-meditation with a
      CD groups reported less distress from baseline and at 6 and 12 weeks, as
      evidenced by the HADS anxiety scale. CONCLUSIONS: This study demonstrated two
      equally effective meditation techniques that can be implemented with patients
      experiencing high stress during radiation treatments in any health care setting
      to decrease patient anxiety, depression, and emotional distress. The data
      established self-meditation with a CD as a more cost-effective alternative to
      meditation with a coach, which requires intensive training and time commitment
      for patients.

PMID- 28437148
TI  - Autism and Mind-Body Therapies: A Systematic Review.
AB  - BACKGROUND: Mind-body therapies are often used by people with autism spectrum
      disorders (ASD). However, there has been little examination into which types of
      mind-body therapies have been investigated for people with ASD and for what
      purposes. A systematic review was conducted to evaluate the existing evidence for
      mind-body therapies for people with ASD, particularly to determine the types of
      mind-body therapies used and the outcomes that are targeted. METHODS: PubMed,
      PsychInfo, and Scopus were searched using terms for ASD and mind-body therapies.
      Sixteen studies were selected for review; these studies tested interventions
      using mindfulness, meditation, yoga, Nei Yang Gong, and acceptance commitment
      therapy. Most study outcomes targeted behavior, psychological symptoms, and
      quality of life for children and adults with ASD as well as their parents.
      RESULTS: There was little overlap between studies on the types of mind-body
      therapies used and associated outcomes, and only three of the studies were
      randomized controlled trials. Most studies were small and uncontrolled. Some
      studies modified the mind-body therapies to increase accessibility for people
      with ASD. CONCLUSION: The evidence for mind-body therapies for people with ASD is
      limited and would benefit from larger randomized controlled trials.

PMID- 28437149
TI  - The Effects of Yoga on Positive Mental Health Among Healthy Adults: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVES: The aim of this study was to present an overview of the research on
      the effects of yoga on positive mental health (PMH) among non-clinical adult
      populations. METHODS: This was a systematic literature review and meta-analysis,
      including a risk of bias assessment. The electronic databases PubMed/Medline,
      Scopus, IndMED, and the Cochrane Library were searched from 1975 to 2015.
      Randomized controlled trials (RCTs) on the effects of yoga interventions on PMH
      among a healthy adult population were selected. RESULTS: A total of 17 RCTs were
      included in the meta-analysis. Four indicators of PMH were found: psychological
      well-being, life satisfaction, social relationships, and mindfulness. A
      significant increase in psychological well-being in favor of yoga over no active
      control was found. Overall risk of bias was unclear due to incomplete reporting.
      CONCLUSIONS: The current body of research offers weak evidence that the practice
      of yoga contributes to an increase in PMH among adults from non-clinical
      populations in general. Yoga was found to contribute to a significant increase in
      psychological well-being when compared to no intervention but not compared to
      physical activity. For life satisfaction (emotional well-being), social
      relationships (social well-being), and mindfulness no significant effects for
      yoga were found over active or non-active controls. Due to the limited amount of
      studies, the heterogeneity of the intervention, and perhaps the way PMH is being
      measured, any definite conclusions on the effects of yoga on PMH cannot be drawn.

PMID- 28437151
TI  - Importance of Costs and Cost Effectiveness of Palliative Care.

PMID- 28437150
TI  - Cost of Cancer-Related Neutropenia or Fever Hospitalizations, United States,
      2012.
AB  - PURPOSE: Neutropenia and subsequent infections are life-threatening treatment
      related toxicities of chemotherapy. Among patients with cancer, hospitalizations
      related to neutropenic complications result in substantial medical costs,
      morbidity, and mortality. Previous estimates for the cost of cancer-related
      neutropenia hospitalizations are based on older and limited data. This study
      provides nationally representative estimates of the cost of cancer-related
      neutropenia hospitalizations. METHODS: We examined data from the 2012 National
      Inpatient Sample and Kids' Inpatient Database. Hospitalizations for cancer
      related neutropenia were defined as those with a primary or secondary diagnosis
      of cancer and a diagnosis of neutropenia or a fever of unknown origin. We
      examined characteristics of cancer-related neutropenia hospitalizations among
      children (age < 18 years) and adults (age >= 18 years). Adjusted predicted
      margins were used to estimate length of stay and cost per stay. RESULTS: There
      were 91,560 and 16,859 cancer-related neutropenia hospitalizations among adults
      and children, respectively. Total cost of cancer-related neutropenia
      hospitalizations was $2.3 billion for adults and $439 million for children.
      Cancer-related neutropenia hospitalizations accounted for 5.2% of all cancer
      related hospitalizations and 8.3% of all cancer-related hospitalization costs.
      For adults, the mean length of stay for cancer-related neutropenia
      hospitalizations was 9.6 days, with a mean hospital cost of $24,770 per stay. For
      children, the mean length of stay for cancer-related neutropenia hospitalizations
      was 8.5 days, with a mean hospital cost of $26,000 per stay. CONCLUSION: We found
      the costs of cancer-related neutropenia hospitalizations to be substantially
      high. Efforts to prevent and minimize neutropenia-related complications among
      patients with cancer may decrease hospitalizations and associated costs.

PMID- 28437152
TI  - Diffuse Marrow Involvement in Metastatic Osteosarcoma: An Unusual Presentation.

PMID- 28437153
TI  - DIABETIC KETOACIDOSIS IN PATIENTS WITH TYPE 2 DIABETES RECENTLY COMMENCED ON SGLT
      2 INHIBITORS: AN ONGOING CONCERN.
AB  - OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly
      used as an adjunctive treatment for type 2 diabetes. We report the occurrence of
      diabetic ketoacidosis (DKA) in 3 patients with type 2 diabetes recently commenced
      on SGLT-2 inhibitors. METHODS: Clinical presentation, laboratory data, and
      treatment outcomes of all 3 cases are described. RESULTS: All 3 patients had
      documented history of longstanding type 2 diabetes. The presentation in all
      patients was that of hyperglycaemia, acidosis, and ketosis occurring within 4
      weeks of commencing SGLT-2 inhibitors. The risk factors for developing DKA were
      infection, myocardial infarction, and alcohol excess. DKA resolved within 24
      hours of initiating intravenous fluids and insulin in all cases. CONCLUSION: This
      case series illustrates the importance of careful patient selection, education,
      and monitoring when starting this group of antidiabetic medications.
      ABBREVIATIONS: DKA = diabetic ketoacidosis SGLT-2 = sodium-glucose cotransporter
      2 T2D = type 2 diabetes.

PMID- 28437154
TI  - PREDICTION OF RELAPSE FROM HYPERTHYROIDISM FOLLOWING ANTITHYROID MEDICATION
      WITHDRAWAL USING TECHNETIUM THYROID UPTAKE SCANNING.
AB  - OBJECTIVE: Technetium thyroid uptake (TTU) is not inhibited by antithyroid drugs
      (ATD) and reflects the degree of thyroid stimulation. We intended to predict the
      relapse rate from hyperthyroidism based on TTU measurement. METHODS: Out of 44
      initially enrolled subjects, 38 patients aged 41.6 +/- 14.6 with Graves disease
      (duration: 84 +/- 78 months) completed the study. TTU was performed with 40
      second imaging of the neck and mediastinum 20 minutes after injection of 1 mCi
      technetium-99m pertechnetate. TTU was measured as the percentage of the count of
      activity accumulated in the thyroidal region minus the mediastinal background
      uptake to the count of 1 mCi technetium-99m under the same acquisition
      conditions. Then methimazole was stopped and patients were followed. The optimal
      TTU cutoff value for Graves relapse prediction was calculated using Youden's J
      statistic. RESULTS: Hyperthyroidism relapsed in 11 (28.9%) patients 122 +/- 96
      (range: 15-290) days post-ATD withdrawal. The subjects in remission were followed
      for 209 +/- 81 days (range: 88-390). TTU was significantly higher in patients
      with forthcoming relapse (12.0 +/- 8.0 vs. 3.9 +/- 2.0, P = .007). The difference
      was significant after adjustment for age, sex, history of previous relapse,
      disease duration, and thyroid-stimulating hormone (TSH) levels before withdrawal.
      The area under the receiver operative characteristic (ROC) curve was 0.87. The
      optimal TTU cutoff value for classification of subjects with relapse and
      remission was 8.7 with sensitivity, specificity, and positive and negative
      predictive value of 73%, 100%, 100%, and 90%, respectively (odds ratio [OR] =
      10.0; 95% confidence interval [CI]: 3.4-29.3). CONCLUSION: TTU evaluation in
      hyperthyroid patients receiving antithyroid medication is an accurate and
      practical method for predicting relapse after ATD withdrawal. ABBREVIATIONS: ATD
      = antithyroid drugs RIU = radio-iodine uptake TSH = thyroid-stimulating hormone
      TSI = thyroid-stimulating immunoglobulin TTU = technetium thyroid uptake.

PMID- 28437155
TI  - Eyelid reconstruction using the "Hughes" tarsoconjunctival advancement flap: Long
      term outcomes in 122 consecutive cases over a 13-year period.
AB  - This article evaluates the complications and long term functional and cosmetic
      outcomes of tarsoconjunctival advancement flaps for repairing a range of lower
      eyelid defects in a large cohort of consecutive cases. A retrospective series of
      122 consecutive cases of eyelid reconstruction using tarsoconjunctival
      advancement flaps was conducted at Waikato Hospital, or Hamilton Eye Clinic, New
      Zealand. All cases of lid reconstruction using tarsoconjunctival-advancement
      flaps between January 1, 2001 until April 3, 2014 were included for analysis. All
      patients provided written consent for surgery and the study complied with New
      Zealand Health and Disability Ethics Committee guidelines and the Declaration of
      Helsinki. Data were collected on patient demographics, lesion histology, defect
      size, adjuvant surgical procedures required for reconstruction, surgical and
      postoperative complications, cosmesis and patient satisfaction. Patients
      requiring lower eyelid reconstruction were predominantly male (56%) and basal
      cell carcinoma was the most common pathology (>80%). Male gender was associated
      with larger tarsoconjunctival-advancement-flap width (P-value = 0.0432), larger
      maximum flap width (20 vs 15 mm), and required on average more adjuvant
      procedures for reconstruction (1.80 vs 1.48, P-value = 0.02). Mean duration to
      flap division was 37 days and decreased over the duration of the study.
      Complicated cases were associated with shorter duration to flap division. Mean
      follow-up was 7 months, complications were observed in 14% with revision required
      in 4%. Tarsoconjunctival flap reconstruction of the lower lid is suitable for a
      range of defect sizes and produces excellent functional and cosmetic outcomes.
      Complications are relatively infrequent and may be associated in some cases with
      decreased duration to flap division.

PMID- 28437156
TI  - Development of a TaqMan-based real-time PCR assay for rapid and specific
      detection of fowl aviadenovirus serotype 4.
AB  - Twelve serotypes of fowl aviadenovirus, namely, FAdV-(1-8a and 8b-11), have been
      identified, among which FAdV-4 is the aetiologic agent of hepatitis
      hydropericardium syndrome (HHS) in chickens. Outbreaks of HHS have been
      documented in many countries, causing significant economic losses. Real-time PCR
      methods described so far in the literature cross-detect different serotypes of
      FAdVs. In this study, we aimed to develop a TaqMan-based real-time PCR assay for
      the specific detection of FAdV-4. A pair of primers targeting the hexon gene and
      a TaqMan probe were designed. Using different copy numbers of plasmid DNA
      carrying the hexon gene as template, we showed the detection limit of this assay
      was 101 copies/reaction, which was 10 times higher than conventional PCR. The
      assay was highly specific for FAdV-4 and did not cross-detect 11 other serotypes
      of FAdVs, avian influenza virus, Newcastle disease virus, infectious bronchitis
      virus or subgroup J of the avian leukosis virus. The reproducibility of the assay
      was assessed by five independent reactions using different copy numbers of
      plasmid DNA (103 and 105) as template, and the results showed 0.56-1.15%
      coefficient of variation for inter-assay variability. Furthermore, the assay was
      validated with 80 clinical samples. Real-time PCR showed that 76 out of 80
      samples were positive for FAdV-4 (95.0% positivity) while 68 out of 80 were
      tested positive by conventional PCR (85.0% positivity). Our data suggest this
      real-time PCR assay could be an attractive tool for screening, confirmatory
      diagnosis and specific differentiation of FAdV-4 infection.

PMID- 28437158
TI  - WVPA XXth Congress 2017.

PMID- 28437159
TI  - Specific Host-Responsive Associations Between Medicago truncatula Accessions and
      Sinorhizobium Strains.
AB  - Legume plants interact with rhizobia to form nitrogen-fixing root nodules. Legume
      rhizobium interactions are specific and only compatible rhizobia and plant
      species will lead to nodule formation. Even within compatible interactions, the
      genotype of both the plant and the bacterial symbiont will impact on the
      efficiency of nodule functioning and nitrogen-fixation activity. The model legume
      Medicago truncatula forms nodules with several species of the Sinorhizobium
      genus. However, the efficiency of these bacterial strains is highly variable. In
      this study, we compared the symbiotic efficiency of Sinorhizobium meliloti
      strains Sm1021, 102F34, and FSM-MA, and Sinorhizobium medicae strain WSM419 on
      the two widely used M. truncatula accessions A17 and R108. The efficiency of the
      interactions was determined by multiple parameters. We found a high effectiveness
      of the FSM-MA strain with both M. truncatula accessions. In contrast, specific
      highly efficient interactions were obtained for the A17-WSM419 and R108-102F34
      combinations. Remarkably, the widely used Sm1021 strain performed weakly on both
      hosts. We showed that Sm1021 efficiently induced nodule organogenesis but cannot
      fully activate the differentiation of the symbiotic nodule cells, explaining its
      weaker performance. These results will be informative for the selection of
      appropriate rhizobium strains in functional studies on symbiosis using these M.
      truncatula accessions, particularly for research focusing on late stages of the
      nodulation process.

PMID- 28437160
TI  - Meeting Report of the XIV International Small Bowel Transplant Symposium: Summary
      of Presentations, Workshops, and Debates From a Comprehensive Meeting on
      Intestinal Failure, Rehabilitation, and Transplantation, Buenos Aires, Argentina,
      June 10-13, 2015.
AB  - The 2015 meeting of the Intestinal Transplant Association was held in Buenos
      Aires, Argentina. This was the 14th International Small Bowel Transplant
      Symposium, and it was the first meeting organized as a joint venture of the
      Transplantation Society, the Intestinal Transplant Association, and the
      Argentinean Transplant Society (Sociedad Argentina de Trasplantes). Innovative
      aspects of the classic meeting format included workshops sessions, debates, and
      multicenter studies. This report highlights the most prominent scientific
      contributions and results of the first such symposium in a Latin American
      country.

PMID- 28437161
TI  - Randomized Phase III Trial of Trastuzumab Plus Capecitabine With or Without
      Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive
      Metastatic Breast Cancer Who Experienced Disease Progression During or After
      Trastuzumab-Based Therapy.
AB  - Purpose To assess the efficacy and safety of trastuzumab plus capecitabine with
      or without pertuzumab in patients with human epidermal growth factor receptor 2
      positive metastatic breast cancer who experienced disease progression during or
      after trastuzumab-based therapy and received a prior taxane. Patients and Methods
      Patients were randomly assigned to arm A: trastuzumab 8 mg/kg -> 6 mg/kg once
      every 3 weeks plus capecitabine 1,250 mg/m2 twice a day (2 weeks on, 1 week off,
      every 3 weeks); or arm B: pertuzumab 840 mg -> 420 mg once every 3 weeks plus
      trastuzumab at the same dose and schedule as arm A plus capecitabine 1,000 mg/m2
      on the same schedule as arm A. The primary end point was independent review
      facility-assessed progression-free survival (IRF PFS). Secondary end points
      included overall survival (OS) and safety. Hierarchical testing procedures were
      used to control type I error for statistical testing of IRF PFS, OS, and
      objective response rate. Results Randomly assigned (intent-to-treat) populations
      were 224 and 228 patients in arms A and B, respectively. Median IRF PFS at 28.6
      and 25.3 months' median follow-up was 9.0 v 11.1 months (hazard ratio, 0.82; 95%
      CI, 0.65 to 1.02; P = .0731) and interim OS was 28.1 v 36.1 months (hazard ratio,
      0.68; 95% CI, 0.51 to 0.90). The most common adverse events (all grades;
      incidence of >= 10% in either arm and >= 5% difference between arms) were hand
      foot syndrome, nausea, and neutropenia in arm A, and diarrhea, rash, and
      nasopharyngitis in arm B. Conclusion The addition of pertuzumab to trastuzumab
      and capecitabine did not significantly improve IRF PFS. An 8-month increase in
      median OS to 36.1 months with pertuzumab was observed. Statistical significance
      for OS cannot be claimed because of the hierarchical testing of OS after the
      primary PFS end point; however, the magnitude of OS difference is in keeping with
      prior experience of pertuzumab in metastatic breast cancer. No new safety signals
      were identified.

PMID- 28437162
TI  - Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I to IIIA
      Completely Resected Non-Small-Cell Lung Cancers: American Society of Clinical
      Oncology/Cancer Care Ontario Clinical Practice Guideline Update.
AB  - Purpose The panel updated the American Society of Clinical Oncology (ASCO)
      adjuvant therapy guideline for resected non-small-cell lung cancers. Methods ASCO
      convened an update panel and conducted a systematic review of the literature,
      investigating adjuvant therapy in resected non-small-cell lung cancers. Results
      The updated evidence base covered questions related to adjuvant systemic therapy
      and included a systematic review conducted by Cancer Care Ontario current to
      January 2016. A recent American Society for Radiation Oncology guideline and
      systematic review, previously endorsed by ASCO, was used as the basis for
      recommendations for adjuvant radiation therapy. An update of these systematic
      reviews and a search for studies related to radiation therapy found no additional
      randomized controlled trials. Recommendations Adjuvant cisplatin-based
      chemotherapy is recommended for routine use in patients with stage IIA, IIB, or
      IIIA disease who have undergone complete surgical resections. For individuals
      with stage IB, adjuvant cisplatin-based chemotherapy is not recommended for
      routine use. However, a postoperative multimodality evaluation, including a
      consultation with a medical oncologist, is recommended to assess benefits and
      risks of adjuvant chemotherapy for each patient. The guideline provides
      information on factors other than stage to consider when making a recommendation
      for adjuvant chemotherapy, including tumor size, histopathologic features, and
      genetic alterations. Adjuvant chemotherapy is not recommended for patients with
      stage IA disease. Adjuvant radiation therapy is not recommended for patients with
      resected stage I or II disease. In patients with stage IIIA N2 disease, adjuvant
      radiation therapy is not recommended for routine use. However, a postoperative
      multimodality evaluation, including a consultation with a radiation oncologist,
      is recommended to assess benefits and risks of adjuvant radiation therapy for
      each patient with N2 disease. Additional information is available at
      www.asco.org/lung-cancer-guidelines and www.asco.org/guidelineswiki .

PMID- 28437163
TI  - Going Beyond Being Lost in Transition: A Decade of Progress in Cancer
      Survivorship.

PMID- 28437164
TI  - Factors Affecting the Levels of Heavy Metals in Juices Processed with Filter
      Aids.
AB  - This study investigated factors that may contribute to the presence of arsenic
      and other heavy metals in apple and grape juices processed with filter aids.
      Different types and grades of filter aids were analyzed for arsenic, lead, and
      cadmium with inductively coupled plasma-tandem mass spectrometry. Potential
      factors affecting the transfer of heavy metals to juices during filtration
      treatments were evaluated. Effects of washing treatments on removal of heavy
      metals from filter aids were also determined. Results showed that diatomaceous
      earth (DE) generally contained a higher level of arsenic than perlite, whereas
      perlite had a higher lead content than DE. Cellulose contained the lowest level
      of arsenic among the surveyed filter aids. All samples of food-grade filter aids
      contained arsenic and lead levels that were below the U.S. Pharmacopeia and
      National Formulary limits of 10 ppm of total leachable arsenic and lead for food
      grade DE filter aids. Two samples of arsenic-rich (>3 ppm) food-grade filter aids
      raised the level of arsenic in apple and grape juices during laboratory-scale
      filtration treatments, whereas three samples of low-arsenic (<1 ppm) food-grade
      filter aids did not affect arsenic levels in filtered juices. Filtration tests
      with simulated juices (pH 2.9 to 4.1, Brix [ degrees Bx] 8.2 to 18.1, total
      suspended solids [TSS] 0.1 to 0.5%) showed that pH or sugar content had no effect
      on arsenic levels of filtered juices, whereas arsenic content of filtered juice
      was elevated when higher amounts of filter aid were used for filtration.
      Authentic unfiltered apple juice (pH 3.6,  degrees Bx 12.9, TSS 0.4%) and grape
      juice (pH 3.3,  degrees Bx 16.2, TSS 0.05%) were used to verify results obtained
      with simulated juices. However, body feed ratio did not affect the arsenic
      content of filtered authentic juices. Washing treatments were effective at
      reducing arsenic, but not cadmium or lead, concentrations in a DE filter aid.
      This study identified ways to reduce the amount of arsenic transferred to juices
      during filtration.

PMID- 28437165
TI  - Survey for Listeria monocytogenes in and on Ready-to-Eat Foods from Retail
      Establishments in the United States (2010 through 2013): Assessing Potential
      Changes of Pathogen Prevalence and Levels in a Decade.
AB  - A multiyear interagency Listeria monocytogenes Market Basket Survey was
      undertaken for selected refrigerated ready-to-eat foods purchased at retail in
      four FoodNet sites in the United States. Food samples from 16 food categories in
      six broad groups (seafood, produce, dairy, meat, eggs, and combination foods)
      were collected weekly at large national chain supermarkets and independent
      grocery stores in California, Maryland, Connecticut, and Georgia for 100 weeks
      between December 2010 and March 2013. Of the 27,389 total samples, 116 samples
      tested positive by the BAX PCR system for L. monocytogenes , and the pathogen was
      isolated and confirmed for 102 samples. Among the 16 food categories, the
      proportion of positive samples (i.e., without considering clustering effects)
      based on recovery of a viable isolate of L. monocytogenes ranged from 0.00% (95%
      confidence interval: 0.00, 0.18) for the category of soft-ripened and semisoft
      cheese to 1.07% (0.63, 1.68) for raw cut vegetables. Among the 571 samples that
      tested positive for Listeria-like organisms, the proportion of positive samples
      ranged from 0.79% (0.45, 1.28) for soft-ripened and semisoft cheese to 4.76%
      (2.80, 7.51) for fresh crab meat or sushi. Across all 16 categories, L.
      monocytogenes contamination was significantly associated with the four states (P
      < 0.05) but not with the packaging location (prepackaged by the manufacturer
      versus made and/or packaged in the store), the type of store (national chain
      versus independent), or the season. Among the 102 samples positive for L.
      monocytogenes , levels ranged from <0.036 most probable number per g to 6.1 log
      CFU/g. For delicatessen (deli) meats, smoked seafood, seafood salads, soft
      ripened and semisoft cheeses, and deli-type salads without meat, the percentage
      of positive samples was significantly lower (P < 0.001) in this survey than that
      reported a decade ago based on comparable surveys in the United States. Use of
      mixed logistic regression models to address clustering effects with regard to the
      stores revealed that L. monocytogenes prevalence ranged from 0.11% (0.03, 0.34)
      for sprouts (prepackaged) to 1.01% (0.58, 1.74) for raw cut vegetables
      (prepackaged).

PMID- 28437166
TI  - Virus-Like Particles of mRNA with Artificial Minimal Coat Proteins: Particle
      Formation, Stability, and Transfection Efficiency.
AB  - RNA has enormous potential as a therapeutic, yet, the successful application
      depends on efficient delivery strategies. In this study, we demonstrate that a
      designed artificial viral coat protein, which self-assembles with DNA to form rod
      shaped virus-like particles (VLPs), also encapsulates and protects mRNA encoding
      enhanced green fluorescent protein (EGFP) and luciferase, and yields cellular
      expression of these proteins. The artificial viral coat protein consists of an
      oligolysine (K12) for binding to the oligonucleotide, a silk protein-like
      midblock S10 = (GAGAGAGQ)10 that self-assembles into stiff rods, and a long
      hydrophilic random coil block C that shields the nucleic acid cargo from its
      environment. With mRNA, the C-S10-K12 protein coassembles to form rod-shaped VLPs
      each encapsulating about one to five mRNA molecules. Inside the rod-shaped VLPs,
      the mRNAs are protected against degradation by RNAses, and VLPs also maintain
      their shape following incubation with serum. Despite the lack of cationic surface
      charge, the mRNA VLPs transfect cells with both EGFP and luciferase, although
      with a much lower efficiency than obtained by a lipoplex transfection reagent.
      The VLPs have a negligible toxicity and minimal hemolytic activity. Our results
      demonstrate that VLPs yield efficient packaging and shielding of mRNA and create
      the basis for implementation of additional virus-like functionalities to improve
      transfection and cell specificity, such as targeting functionalities.

PMID- 28437167
TI  - The FgVps39-FgVam7-FgSso1 Complex Mediates Vesicle Trafficking and Is Important
      for the Development and Virulence of Fusarium graminearum.
AB  - Vesicle trafficking is an important event in eukaryotic organisms. Many proteins
      and lipids transported between different organelles or compartments are essential
      for survival. These processes are mediated by soluble N-ethylmaleimide-sensitive
      factor attachment protein receptor (SNARE) proteins, Rab-GTPases, and
      multisubunit tethering complexes such as class C core vacuole or endosome
      tethering and homotypic fusion or vacuole protein sorting (HOPS). Our previous
      study has demonstrated that FgVam7, which encodes a SNARE protein involving in
      vesicle trafficking, plays crucial roles in growth, asexual or sexual
      development, deoxynivalenol production, and pathogenicity in Fusarium
      graminearum. Here, the affinity purification approach was used to identify FgVam7
      interacting proteins to explore its regulatory mechanisms during vesicle
      trafficking. The orthologs of yeast Vps39, a HOPS tethering complex subunit, and
      Sso1, a SNARE protein localized to the vacuole or endosome, were identified and
      selected for further characterization. In yeast two-hybrid and glutathione-S
      transferase pull-down assays, FgVam7, FgVps39, and FgSso1 interacted with each
      other as a complex. The ?Fgvps39 mutant generated by targeted deletion was
      significantly reduced in vegetative growth and asexual development. It failed to
      produce sexual spores and was defective in plant infection and deoxynivalenol
      production. Further cellular localization and cytological examinations suggested
      that FgVps39 is involved in vesicle trafficking from early or late endosomes to
      vacuoles in F. graminearum. Additionally, the ?Fgvps39 mutant was defective in
      vacuole morphology and autophagy, and it was delayed in endocytosis. Our results
      demonstrate that FgVam7 interacts with FgVps39 and FgSso1 to form a unique
      complex, which is involved in vesicle trafficking and modulating the proper
      development of infection-related morphogenesis in F. graminearum.

PMID- 28437168
TI  - Regulation of PTEN degradation and NEDD4-1 E3 ligase activity by Numb.
AB  - The critical tumor suppressor PTEN is regulated by numerous post-translational
      modifications including phosphorylation, acetylation and ubiquitination.
      Ubiquitination of PTEN was reported to control both PTEN stability and nuclear
      localization. Notably, the HECT E3-ligase NEDD4-1 was identified as the ubiquitin
      ligase for PTEN, mediating its degradation and down-stream events. However, the
      mechanisms how NEDD4-1 is regulated by up-stream signaling pathways or
      interaction with other proteins in promoting PTEN degradation remain largely
      unclear. In the present study, we identified that the adaptor protein Numb, which
      is demonstrated to be a novel binding partner of NEDD4-1, plays important roles
      in controlling PTEN ubiquitination through regulating NEDD4-1 activity and the
      association between PTEN and NEDD4-1. Furthermore, we provided data to show that
      Numb regulates cell proliferation and glucose metabolism in a PTEN-dependent
      manner. Overall, our study revealed a novel regulation of the well-documented
      NEDD4-1/PTEN pathway and its oncogenic behavior.

PMID- 28437169
TI  - Re: Multiple Tumor Excisions in Ipsilateral Kidney Increase Complications After
      Partial Nephrectomy (From: Maurice MJ, Ramirez D, Nelson R, et al. J Endourology
      2016;30:1200-1206).

PMID- 28437170
TI  - Prostate Specific Antigen Nadir of 0.1 or Less Is a Predictor of Treatment
      Success in Men Undergoing Salvage Whole Prostate Gland Cryoablation.
AB  - PURPOSE: To assess factors that affect prostate biopsy results following salvage
      whole gland cryoablation. PATIENTS AND METHODS: One hundred seventy-four patients
      underwent prostate biopsy following salvage whole gland cryoablation of the
      prostate in the Cryo-OnLine Database registry. Wilcoxon rank-sum and chi2 tests
      and logistic regression analysis were used to assess predictors of positive
      biopsy. Prostate specific antigen (PSA) nadir was divided into a statistical
      tertile for comparisons between different nadir PSA cut points. RESULTS: Fifty
      two of 174 (29.9%) of this highly select group of men who underwent biopsy had a
      posttreatment biopsy demonstrating malignant cancer. Men who had positive biopsy
      following salvage therapy had significantly higher median nadir PSA, shorter
      median time to prostate biopsy, and shorter median time to biochemical failure.
      Compared to the lowest tertile (PSA nadir defined as <=0.1 ng/mL), PSA in the
      second tertile (0.11-0.8 ng/mL) and third tertile (>0.8 ng/mL) demonstrated
      increased odds ratio (OR) for positive biopsy, 4.34 (95% confidence interval [CI]
      1.66, 11.4, p = 0.003) and 2.81 (95% CI 1.14, 7.00, p = 0.02), respectively, in
      adjusted models. In addition, men with a presalvage PSA >20 (OR 7.65; 95% CI
      2.03, 28.9; p = 0.003) and Gleason score >=8 (OR 2.26; 95% CI 0.93, 5.47; p =
      0.07) had a higher OR of positive biopsy. CONCLUSIONS: Nadir PSA of 0.1 ng/mL or
      less following salvage cryotherapy is predictive of treatment success. Routine
      biopsy should be reserved for men with nadir PSA >0.1 ng/mL and patients with
      high risk features of prostate cancer before salvage cryoablation.

PMID- 28437171
TI  - Psychological Benefits of Yoga for Female Inmates.
AB  - Female inmates involved in the Yoga Prison Project at two correctional facilities
      in South Carolina served as subjects. Inmates were selected from those who
      applied to participate in a ten-week trauma-focused yoga program. To create
      control and experimental groups, inmates who requested to participate were
      randomly assigned to be in the class (Treatment Group, n = 33) or a waitlist
      (Control Group, n = 17). Inmates on the waitlist subsequently joined the next
      class, so all who applied and were eligible participated in a yoga class.
      Measures of stress, depression, self control, anxiety, self awareness and
      rumination were used and data was collected from both groups before the initial
      yoga class began and again at the end, ten weeks later. To assess the changes
      from pre-intervention to post-intervention, mixed design ANOVA tests were
      conducted. Inmates in the yoga group reported significant decreases in depression
      andstress and improved self-awareness. No significant changes were found on
      measures of anxiety, rumination and self-control in the yoga groups. Although not
      statistically significant, anxiety scores did decrease and self-control scores
      improved for the yoga group, while inmates in the control group reported a
      worsening or no change on these two measures. No changes were found in rumination
      levels. The results suggest that Yoga is a relatively inexpensive intervention
      that could benefit both inmates and prison staff by reducing some negative
      behaviors and possibly mental health problems.

PMID- 28437172
TI  - Analyzing Locomotor Activity in Zebrafish Larvae Using wrMTrck.
AB  - The zebrafish has emerged as a new model system in behavioral neurobiology
      research. There are numerous assays available to analyze locomotor behavior, but
      most of these assays require sophisticated equipment and proprietary software. A
      freely available plugin, wrMTrck, originally developed to analyze locomotor
      response in Caenorhabditis elegans, has been used in this study to measure
      locomotion in zebrafish.

PMID- 28437173
TI  - The Karyotype of Microsternarchus aff. bilineatus: A First Case of Y Chromosome
      Degeneration in Gymnotiformes.
AB  - Various species and lineages that until recently were identified as
      Microsternarchus bilineatus (Hypopomidae, Gymnotiformes) have a widespread
      distribution in the Amazon and Orinoco River basins and across the Guiana shield.
      Recent molecular studies show five distinct lineages for Microsternarchus from
      different localities. These results suggest that this previously monotypic genus
      actually consists of more than one species. Here, we describe the karyotype of M.
      aff. bilineatus from the Cururutuia River (Braganca, Para, Brazil). The diploid
      number of 48 chromosomes (14 meta-submetacentric/34 subtelo-acrocentric) is found
      for males and females, with an XX/XY sex chromosome system. The nucleolar
      organizer region is found in the short arm of pair 9. Constitutive
      heterochromatin occurs in the pericentromeric region of all chromosomes, in the
      distal region of 3p, 5p, 7p, 8q, 9q, 16q, and Xq, in the interstitial region in
      2p, 10q, 11q, and 12q and all along 4p, and in a large block of the Y chromosome.
      These results indicate extensive karyotype divergence between this population and
      samples from Igarape Taruma Grande (Negro River, Amazonas, Brazil) studied by
      other researchers. Moreover, despite the diversity of sex chromosome systems
      found in Gymnotiformes, the XX/XY sex chromosome system of M. aff. bilineatus is
      the first case of Y chromosome degeneration in this order. The present data are
      valuable to help understand karyotype evolution in Hypopomidae.

PMID- 28437174
TI  - More than Fever: Thermoregulatory Responses to Immunological Stimulation and
      Consequences of Thermoregulatory Strategy on Innate Immunity in Gopher Tortoises
      (Gopherus polyphemus).
AB  - Organisms possess a range of thermoregulatory strategies that may vary in
      response to sickness, thereby driving important life-history consequences.
      Because the immune system is vital to maintaining organism function,
      understanding the suite of immune responses to infection indicates basic costs
      and benefits of physiological strategies. Here, we assessed consequences of
      thermoregulation and seasonality on immune function in both immunologically
      stimulated and nonstimulated gopher tortoises (Gopherus polyphemus). An
      ectothermic vertebrate was used as an experimental model because the effects of
      thermoregulation on immunity remain understudied and are of increasing importance
      in light of anthropogenic alterations to thermal environments. We found that G.
      polyphemus increased body temperature (Tb) at 1 h after injection with
      lipopolysaccharide (LPS) when compared with saline controls (P = 0.04),
      consistent with behavioral fever. LPS increased plasma bactericidal ability (BA;
      P = 0.006), reduced plasma iron concentration (P = 0.041), and increased
      heterophil?lymphocyte ratios (P < 0.001). In nonstimulated animals,
      thermoregulatory strategy had a strong effect on innate immunity, which
      demonstrated that individuals have the ability to facultatively adjust immune
      function when infection burden is low; this relationship was not present in LPS
      injected animals, which suggested that animals stimulated with LPS maximize
      bactericidal ability independently of temperature. Seasonal acclimation state did
      not influence responses to LPS, although baseline plasma iron was significantly
      lower in animals acclimated to winter. These results support that a trade-off
      exists between immunity and other conflicting physiological interests. Moreover,
      these results clearly demonstrate the ability of individuals to modulate immune
      function as a direct result of thermoregulatory decisions.

PMID- 28437175
TI  - Pharmacokinetics and Safety of Travoprost 0.004% Ophthalmic Solution Preserved
      with Polyquad in Pediatric Patients with Glaucoma.
AB  - PURPOSE: To evaluate the systemic pharmacokinetics (PKs) of travoprost 0.004%
      preserved with Polyquad(r) (TRAVATAN(r)) in pediatric patients with glaucoma or
      ocular hypertension. METHODS: This was a phase 1, open-label, multicenter
      clinical study of patients aged >=2 months to <18 years. Patients received daily
      administration of travoprost 0.004% preserved with Polyquad in both eyes for 7
      days. Plasma samples were collected 30 min before the final dose and at 10, 20,
      40, and 80 min postdose. The main outcome measure was maximum concentration of
      travoprost free acid in plasma (Cmax). RESULTS: Included in the PK analysis were
      24 patients (average age 9.6 +/- 4.9 years). At least 1 sample with quantifiable
      levels of travoprost free acid was collected for 11 patients. The mean Cmax was
      0.0471 +/- 0.0105 ng/mL for patients aged 2 months to <3 years; 0.0258 +/- 0.0128
      ng/mL for ages 3 to <12 years; and 0.0109 +/- 0.0005 ng/mL for ages 12 to <18
      years. Travoprost was undetectable in samples collected predose from pediatric
      patients. Treatment-related adverse events (AEs) included hyperemia, eye pain,
      and eye pruritus (n = 1 each). There were no discontinuations or drug-related
      serious AEs. CONCLUSIONS: Travoprost free acid concentration in plasma was low in
      pediatric patients, detectable in only 11 of 24 patients. There was no
      accumulation of travoprost over the course of treatment. No clear relationship
      was observed between age/body surface area and Cmax. No increased risk was
      identified for the use of travoprost 0.004% preserved with Polyquad in patients
      <18 years of age.

PMID- 28437176
TI  - Echinocandins in Ocular Therapeutics.
AB  - Fungal infections of the eye, especially fungal keratitis and endophthalmitis,
      are major causes of concern and if left untreated could lead to vision loss.
      Currently, natamycin (polyene antifungal) is the only commercially available
      topical agent used for the treatment of ocular fungal infections. The other
      antifungals, belonging to the polyene and azole classes, are used off-label in
      treating ocular infections and are administered topically, orally, intraocularly,
      or systemically. Even though their use through the different routes of
      administration has shown favorable outcomes, challenges such as poor ocular
      penetration, low bioavailability, ocular toxicity, and systemic side effects
      limit their utility. Hence, in search of alternative strategies, the echinocandin
      class of antifungals are currently being assessed for their use in ocular
      infections. Their evaluation in the ophthalmic arena has been propelled by their
      efficacy, safety, and tolerability reports in the treatment of systemic invasive
      fungal infections. This review compiles the reports on the ocular investigations
      of the 3 commercially available echinocandins-caspofungin, micafungin, and
      anidulafungin-to understand their potential as ocular antifungal agents.

PMID- 28437178
TI  - * An Injectable Recombinant Collagen I Peptide-Based Macroporous Microcarrier
      Allows Superior Expansion of C2C12 and Human Bone Marrow-Derived Mesenchymal
      Stromal Cells and Supports Deposition of Mineralized Matrix.
AB  - The development of scaffold formulations based on extracellular matrix (ECM)
      inspired synthetic materials constitutes an important resource for the advance of
      cell-based therapies in bone tissue engineering approaches, where both cell and
      scaffold implantation are often needed. Culturing cells on porous microcarriers
      (MCs) allows cell expansion in a three-dimensional microenvironment and
      constitutes a possible solution for minimally invasive cell and scaffold
      simultaneous delivery, but the reduced pore dimension and pore interconnection
      diameter of several commercially available MCs limits de facto cell ingrowth, and
      ultimately their suitability for in vivo cell delivery. In this study we
      investigated the potential of a new macroporous MC based on a collagen I-based
      recombinant peptide (CellnestTM) for C2C12 cells and human bone marrow-derived
      mesenchymal stromal cells (hBMSCs) expansion and we analyzed the influence of
      dehydrothermal (DHT), hexamethylene diisocyanate (HMDIC), and 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC) cross-linking strategies on cell vitality,
      proliferation, and hBMSCs differentiation. We established a double emulsification
      protocol for the manufacturing of MCs characterized by external pores of 20-40
      MUm diameter, 73% porosity, and 20 +/- 3 MUm pore interconnection diameter
      supporting cell ingrowth and proliferation into the MC. MCs cross-linked with DHT
      and HMDIC supported higher cell proliferation comparing to a commercially
      available equivalent over the course of 7 days and resulted in higher cell yield
      by day 28. Moreover, while hBMSCs expansion on Cellnest-MCs did not lead to a
      significant upregulation of the early markers of osteogenic differentiation
      Col1a1 and Runx2, their differentiation potential into the osteogenic lineage was
      preserved when cultured in differentiation medium, as confirmed by mineralized
      ECM deposition. We believe that Cellnest-MCs will help in reaching clinically
      relevant cell quantities and ultimately help in accelerating the translation of
      cell-based therapies for bone tissue engineering in the clinical practice.

PMID- 28437177
TI  - Periodontal-Derived Mesenchymal Cell Sheets Promote Periodontal Regeneration in
      Inflammatory Microenvironment.
AB  - In this study, we investigated the periodontal regenerative potential of dental
      follicle cell (DFC) sheets and periodontal ligament cell (PDLC) sheets in the
      simulating inflammatory microenvironment of periodontitis, to confirm their
      regenerative potential for clinical application and explain the possible
      mechanism. The biological characteristics of DFC sheets and PDLC sheets were
      explored in lipopolysaccharide from Porphyromonas gingivalis (P. gingivalis LPS)
      induced inflammation microenvironment in vitro, then cell sheets were
      transplanted into canine periodontal defects with experimental periodontitis in
      situ for 3 months. The results showed that P. gingivalis LPS greatly impaired the
      differentiation of PDLC sheets, whereas promoted gene expression of bone
      sialoprotein (BSP), osteopontin (OPN), and periostin (POSTN) in DFC sheets. LPS
      activated toll-like receptor 4 and NF-kappaB p65 phosphorylation in PDLC sheets.
      In experimental periodontitis, new periodontal attachment could be obtained in
      both PDLC sheets and DFC sheets. However, the complete periodontal regeneration,
      including periodontal ligament-cementum complex structure was observed only in
      DFC sheet groups, which also showed more alveolar bone formation than PDLC
      sheets. These results suggest that DFC sheets were more effective for periodontal
      regeneration in chronic inflammatory microenvironment of periodontitis. It is
      probably because of their ability to adapt the inflammatory environment and
      strong capacity to promote periodontal regeneration. This approach provides a
      tangible pathway toward clinical translation.

PMID- 28437179
TI  - Mechanically Oriented 3D Collagen Hydrogel for Directing Neurite Growth.
AB  - Recent studies in the field of neuro-tissue engineering have demonstrated the
      promising effects of aligned contact guidance cue to scaffolds of enhancement and
      direction of neuronal growth. In vivo, neurons grow and develop neurites in a
      complex three-dimensional (3D) extracellular matrix (ECM) surrounding. Studies
      have utilized hydrogel scaffolds derived from ECM molecules to better simulate
      natural growth. While many efforts have been made to control neuronal growth on
      2D surfaces, the development of 3D scaffolds with an elaborate oriented
      topography to direct neuronal growth still remains a challenge. In this study, we
      designed a method for growing neurons in an aligned and oriented 3D collagen
      hydrogel. We aligned collagen fibers by inducing controlled uniaxial strain on
      gels. To examine the collagen hydrogel as a suitable scaffold for neuronal
      growth, we evaluated the physical properties of the hydrogel and measured
      collagen fiber properties. By combining the neuronal culture in 3D collagen
      hydrogels with strain-induced alignment, we were able to direct neuronal growth
      in the direction of the aligned collagen matrix. Quantitative evaluation of
      neurite extension and directionality within aligned gels was performed. The
      analysis showed neurite growth aligned with collagen matrix orientation, while
      maintaining the advantageous 3D growth.

PMID- 28437180
TI  - A Drug-Induced Hybrid Electrospun Poly-Capro-Lactone: Cell-Derived Extracellular
      Matrix Scaffold for Liver Tissue Engineering.
AB  - Liver transplant is the only treatment option for patients with end-stage liver
      failure, however, there are too few donor livers available for transplant. Whole
      organ tissue engineering presents a potential solution to the problem of rapidly
      escalating donor liver shortages worldwide. A major challenge for liver tissue
      engineers is the creation of a hepatocyte microenvironment; a niche in which
      liver cells can survive and function optimally. While polymers and decellularized
      tissues pose an attractive option for scaffold manufacturing, neither alone has
      thus far proved sufficient. This study exploited cell's native extracellular
      matrix (ECM) producing capabilities using two different histone deacetylase
      inhibitors, and combined these with the customizability and reproducibility of
      electrospun polymer scaffolds to produce a "best of both worlds" niche
      microenvironment for hepatocytes. The resulting hybrid poly-capro-lactone (PCL)
      ECM scaffolds were validated using HepG2 hepatocytes. The hybrid PCL-ECM
      scaffolds maintained hepatocyte growth and function, as evidenced by metabolic
      activity and DNA quantitation. Mechanical testing revealed little significant
      difference between scaffolds, indicating that cells were responding to a
      biochemical and topographical profile rather than mechanical changes.
      Immunohistochemistry showed that the biochemical profile of the drug-derived and
      nondrug-derived ECMs differed in ratio of Collagen I, Laminin, and Fibronectin.
      Furthermore, the hybrid PCL-ECM scaffolds influence the gene expression profile
      of the HepG2s drastically; with expression of Albumin, Cytochrome P450 Family 1
      Subfamily A Polypeptide 1, Cytochrome P450 Family 1 Subfamily A Polypeptide 2,
      Cytochrome P450 Family 3 Subfamily A Polypeptide 4, Fibronectin, Collagen I, and
      Collagen IV undergoing significant changes. Our results demonstrate that drug
      induced hybrid PCL-ECM scaffolds provide a viable, translatable platform for
      creating a niche microenvironment for hepatocytes, supporting in vivo phenotype
      and function. These scaffolds offer great potential for tissue engineering and
      regenerative medicine strategies for whole organ tissue engineering.

PMID- 28437181
TI  - Isolation of Brucella inopinata-Like Bacteria from White's and Denny's Tree
      Frogs.
AB  - Brucella inopinata strain BO1 and B. sp. strain BO2 isolated from human patients,
      respectively, are genetically different from classical Brucella species. We
      isolated bacteria of the genus Brucella from two species of wild-caught tropical
      frogs kept in the facilities in Japan: White's tree frog, which inhabits Oceania,
      and Denny's tree frog, which inhabits Southeast Asia. Phylogenetic analyses based
      on 16S rRNA and recA gene sequences and multilocus sequence analysis showed that
      two isolates of Brucella spp. showed significant similarity to BO1, BO2, and the
      isolates from other wild-caught frogs. These results suggest that a variety of
      frog species are susceptible to a novel clade of Brucella bacteria, including B.
      inopinata.

PMID- 28437182
TI  - First Report of Toxoplasma gondii Infection in Common Quails (Coturnix coturnix)
      Intended for Human Consumption in Three Provinces of Northeastern China.
AB  - Common quails are nutritious food and are also used as medicine in some parts of
      the world. Until now, no information on Toxoplasma gondii infection in common
      quails intended for human consumption in China is available. Therefore, this
      study was carried out to determine the prevalence of T. gondii infection in
      common quails in six cities from Shandong, Liaoning, and Jilin provinces, China.
      Out of 620 common quails examined, 59 (9.52%) were seropositive for T. gondii by
      the modified agglutination test. T. gondii infection in male and female common
      quails was 8.10% and 10.71%, respectively. The highest prevalence (13.10%) was
      detected in a group of common quails from Rizhao of Shandong province, followed
      by common quails from Yantai of Shandong province (13.04%) and the lowest
      prevalence (5.56%) was detected in a group of common quails from Shenyang of
      Liaoning province. The results of this survey revealed the presence of T. gondii
      infection in common quails in China, indicating that common quails are a
      potential source for transmission of T. gondii to humans, therefore, posing a
      potential public health concern. To our knowledge, this is the first report of T.
      gondii infection in common quails in China.

PMID- 28437183
TI  - First Two Imported Cases of Zika Virus Infections in Romania.
AB  - We report the first two cases of imported Zika virus (ZIKV) infection in Romanian
      patients returning from areas with ongoing outbreaks and challenges for
      laboratory diagnostic; first one with a classical pattern of acute flaviviral
      infection and the second one with an interesting pattern of a secondary
      flaviviral (ZIKV) infection in a yellow fever-vaccinated child living abroad in
      an endemic area.

PMID- 28437184
TI  - Control of Mosquito-Borne Diseases in Northwestern Italy: Preparedness from One
      Season to the Next.
AB  - INTRODUCTION: Mosquito-borne diseases (MBDs) are spreading worldwide due to
      globalization and climate change, representing a threat for both humans and
      animals. Of great concern are the infections caused by viruses belonging to the
      Flavivirus genus as West Nile virus (WNV) and Usutu virus (USUV) transmitted by
      Culex sp. or Dengue virus and Zika virus (ZIKV), transmitted by Aedes sp. This
      work describes the surveillance protocol enforced in Piedmont (Northwestern
      Italy) to control MBDs spread, focusing on the activities performed on mosquitoes
      during the 2015 vector season. MATERIALS AND METHODS: From July to October,
      mosquitoes were fortnightly sampled in 50 selected sites according to risk
      factors with CDC dry ice-baited traps and BG-Sentinel traps baited with BG-Lure
      and dry ice. Adults were counted, identified to species level, pooled, and
      screened for flaviviruses using different reverse transcription-PCR protocols and
      sequencing. Finally, phylogenetic analysis was performed on a dataset including
      2014 and 2015 WNV sequences and reference sequences retrieved from GenBank.
      RESULTS AND DISCUSSION: A total of 17,000 mosquitoes, grouped in 730 pools, were
      tested. Five pools of Culex pipiens were positive for WNV Lineage 2 in Novara,
      Alessandria, Vercelli, and Torino Provinces. One pool of C. pipiens and one pool
      of Anopheles maculipennis s.l. were positive for USUV in Vercelli and Alessandria
      Provinces. In Vercelli Province one pool of C. pipiens resulted positive both for
      WNV and USUV. Control measures were quickly implemented. Phylogenetic analyses
      showed that the WNV Lin 2 sequences from Piedmont region cluster with those
      circulating in Northeastern Italy in the previous years. Given the positive trend
      in WNV activity compared to 2014 and the emergence caused by other flavivirus as
      ZIKV, the level of attention for the 2016 vector season may be increased and this
      surveillance protocol could represent an important tool for public health
      authorities.

PMID- 28437185
TI  - Absence of Evidence of Rift Valley Fever Infection in Eulemur fulvus (Brown
      Lemur) in Mayotte During an Interepidemic Period.
AB  - The potential role of Eulemur fulvus (brown lemur) in the epidemiology of Rift
      Valley fever (RVF) in Mayotte, during an interepidemic period, was explored. In
      February and March 2016, 72 animals were blood sampled and tested for RVF. No
      evidence of RVF genome or antibodies was found in the samples. The role of other
      wild mammals on the island should, however, be further investigated.

PMID- 28437186
TI  - Leptospira Species in Feral Cats and Black Rats from Western Australia and
      Christmas Island.
AB  - Leptospirosis is a neglected, re-emerging bacterial disease with both zoonotic
      and conservation implications. Rats and livestock are considered the usual
      sources of human infection, but all mammalian species are capable of carrying
      Leptospira spp. and transmitting pathogenic leptospires in their urine, and
      uncertainty remains about the ecology and transmission dynamics of Leptospira in
      different regions. In light of a recent case of human leptospirosis on tropical
      Christmas Island, this study aimed to investigate the role of introduced animals
      (feral cats and black rats) as carriers of pathogenic Leptospira spp. on
      Christmas Island and to compare this with two different climatic regions of
      Western Australia (one island and one mainland). Kidney samples were collected
      from black rats (n = 68) and feral cats (n = 59) from Christmas Island, as well
      as feral cats from Dirk Hartog Island (n = 23) and southwest Western Australia (n
      = 59). Molecular (PCR) screening detected pathogenic leptospires in 42.4% (95%
      confidence interval 29.6-55.9) of cats and 2.9% (0.4-10.2) of rats from Christmas
      Island. Sequencing of cat- and rat-positive samples from Christmas Island showed
      100% similarity for Leptospira interrogans. Pathogenic leptospires were not
      detected in cats from Dirk Hartog Island or southwest Western Australia. These
      findings were consistent with previous reports of higher Leptospira spp.
      prevalence in tropical regions compared with arid and temperate regions. Despite
      the abundance of black rats on Christmas Island, feral cats appear to be the more
      important reservoir species for the persistence of pathogenic L. interrogans on
      the island. This research highlights the importance of disease surveillance and
      feral animal management to effectively control potential disease transmission.

PMID- 28437187
TI  - Synergy Between Choroid Plexus Epithelial Cell-Conditioned Medium and Knockout
      Serum Replacement Converts Human Adipose-Derived Stem Cells to Dopamine-Secreting
      Neurons.
AB  - Human adipose-derived stem cells (hADSCs) have great capacity to differentiate
      into mesodermal origins as well as nonmesodermal lineages, including neural
      cells. This valuable feature paves the way for the therapeutic application of
      hADSCs for neurodegenerative maladies such as Parkinson's disease (PD). We tested
      the capacity of choroid plexus epithelial cell-conditioned medium (CPEC-CM) alone
      or cocktailed with knockout serum (KS) to induce dopaminergic (DAergic)
      differentiation of hADSCs. To this end, hADSCs from lipoaspirate were
      phenotypically characterized and shown to maintain mesodermal multipotency so
      that selected media easily differentiated them into osteoblasts, chondrocytes,
      and adipocytes. To begin inducing hADSC neuronal differentiation, we isolated
      CPECs from rat brain and expanded them in culture to obtain CPEC-CM. We then
      treated hADSCs with optimized quantities of collected CPEC-CM, KS, or both. The
      ADSCs treated with either CPEC-CM or CPEC-CM and KS displayed morphological
      changes typical of neuron-like phenotypes. As revealed by reverse transcription
      polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), and
      immunostaining analyses, hADSCs cotreated with CPEC-CM and KS expressed
      significantly higher levels of neuronal and DAergic markers in comparison with
      single-treated groups. Moreover, the hADSCs began expressing dopamine
      biosynthesizing enzymes mainly after cotreatment with CPEC-CM and KS.
      Consequently, only cotreated hADSCs were capable of synthesizing and releasing
      dopamine detectable by high-performance liquid chromatography (HPLC). Finally,
      hADSCs growing in an ordinary medium were found positive for astrocytic marker
      glial fibrillary acidic protein (GFAP), but stopped GFAP expression on either
      single or cotreatments. These combined results suggest that CPEC-CM and KS can
      synergize to remarkably augment DAergic induction of hADSCs, an effect that has
      implications for cell replacement therapy for PD and related disorders.

PMID- 28437188
TI  - Further Characterization of the Mitigation of Radiation Lethality by Protective
      Wounding.
AB  - There continues to be a major effort in the United States to develop mitigators
      for the treatment of mass casualties that received high-intensity acute ionizing
      radiation exposures from the detonation of an improvised nuclear device during a
      radiological terrorist attack. The ideal countermeasure should be effective when
      administered after exposure, and over a wide range of absorbed doses. We have
      previously shown that the administration of a subcutaneous incision of a defined
      length, if administered within minutes after irradiation, protected young adult
      female C57BL/6 mice against radiation-induced lethality, and increased survival
      after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%. We refer
      to this approach as "protective wounding". In this article, we report on our
      efforts to further optimize, characterize and demonstrate the validity of the
      protective wounding response by comparing the response of female and male mice,
      varying the radiation dose, the size of the wound, and the timing of wounding
      with respect to administration of the radiation dose. Both male and female mice
      that received a subcutaneous incision after irradiation were significantly
      protected from radiation lethality. We observed that the extent of protection
      against lethality after an LD50/30 X-ray dose was independent of the size of the
      subcutaneous cut, and that a 3 mm subcutaneous incision is effective at enhancing
      the survival of mice exposed to a broad range of radiation doses (LD15-LD100).
      Over the range of 6.2-6.7 Gy, the increase in survival observed in mice that
      received an incision was associated with an enhanced recovery of hematopoiesis.
      The enhanced rate of recovery of hematopoiesis was preceded by an increase in the
      production of a select group of cytokines. Thus, a thorough knowledge of the
      timing of the cytokine cascade after wounding could aid in the development of
      novel pharmacological radiation countermeasures that can be administered several
      days after the actual radiation exposure.

PMID- 28437189
TI  - Metformin Attenuates Radiation-Induced Pulmonary Fibrosis in a Murine Model.
AB  - While radiotherapy continues to be a major cancer treatment option, its dose
      limiting side effects, such as pulmonary fibrosis, severely impair the quality of
      life in these patients. In this study, we evaluated the radioprotective effects
      of metformin, a commonly used biguanide antidiabetic medication, in a murine
      model of pulmonary damage. Sprague Dawley(r) rats received whole lung 20 Gy
      irradiation with or without metformin treatment. Computed tomography (CT) was
      performed and Hounsfield units (HU) were determined during the observation
      period. Histological analysis and evaluation of fibrosis/inflammatory markers by
      Western blot were performed at 12 weeks postirradiation. CCK-8 and colony
      formation assays were used to explore the effects of metformin on non-small cell
      lung cancer cells A549 and H460. Results of this study showed that metformin
      reduced radiological and histological signs of fibrosis, inflammatory
      infiltration, alterations to alveolar structures and radiation-induced HU lung
      density. In addition, metformin was found to significantly decrease collagen 1a
      and TGF-beta expression and inhibit p-Smad2 and p-Smad3 expression compared to
      that of the irradiated group alone. Moreover, metformin reduced A549 and H460
      cell growth and clonogenic survival. In conclusion, metformin exerted a
      protective effect on normal tissues from radiation-induced pulmonary injury, and
      shows promise as a radioprotective agent in the treatment of lung cancer.

PMID- 28437191
TI  - Analysis of Human Tooth Pulp Chamber Temperature After 670 nm Laser Irradiation:
      In Vitro Study.
AB  - OBJECTIVE: One of the limiting factors of employing laser radiation on dental
      therapies is the potential of causing thermal injuries to pulp tissues. The
      purpose of this study was to evaluate intra-chamber temperature increase on
      extracted human teeth exposed to 670 nm wavelength InGaAlP laser diode radiation.
      MATERIALS AND METHODS: In vitro intra-chamber temperature measurements of 12
      standardized human teeth (incisors, canines, premolars, and molars; n = 3) were
      taken both before and after laser radiation. A type-K thermocouple fast-response
      thermocouple wire with a 0.5 mm diameter probe was inserted into the tooth pulp
      chamber (ICEL-Manaus-brand). The laser device Lasotronic-brand InGaAlP laser
      diode was used to irradiate tooth enamel, perpendicularly to the external surface
      for 30 sec, with power of levels of 340, 272, 204, 136, and 68 mW. The
      measurements were taken at three time points: 0, 30 sec, and 3 min after the
      laser irradiation. Measurements were repeated 24 h after removal and reinsertion
      of the probe in the pulp chamber. The temperature gradient (DeltaT in  degrees C)
      was calculated (DeltaT = final temperature-initial temperature) for each group.
      Data of DeltaT were statistically analyzed by two-way analysis of variance
      (ANOVA) at the 95% confidence level and compared by Tukey post hoc test (alpha =
      0.05). RESULTS: ANOVA showed statistically significant differences to the
      interaction of factors (p < 0.05). The highest DeltaT values obtained were
      observed to incisors with 340 mW, 272 mW; 204 mW of power (respectively 4.7
      degrees C, 4.2 degrees C, and 3.1 degrees C); and canines presented the lowest
      DeltaT (0.8 degrees C-0.3 degrees C) with no influence of power output.
      CONCLUSIONS: Since the thermal increase was observed in this study, especially in
      incisors, attention should be paid to avoid pulpal damage.

PMID- 28437190
TI  - Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally
      Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of
      Two Phase 1 Clinical Trials.
AB  - Ketogenic diets are low in carbohydrates and high in fat, which forces cells to
      rely more heavily upon mitochondrial oxidation of fatty acids for energy.
      Relative to normal cells, cancer cells are believed to exist under a condition of
      chronic mitochondrial oxidative stress that is compensated for by increases in
      glucose metabolism to generate reducing equivalents. In this study we tested the
      hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would
      be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC)
      and pancreatic cancer and could potentially exploit cancer cell oxidative
      metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic
      cancer xenografts were fed either a ketogenic diet or standard rodent chow,
      treated with conventionally fractionated radiation (2 Gy/fraction), and tumor
      growth rates were assessed daily. Tumors were assessed for immunoreactive 4
      hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based
      on this and another previously published preclinical study, phase 1 clinical
      trials in locally advanced NSCLC and pancreatic cancer were initiated, combining
      standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC)
      or five weeks (pancreatic cancer). The xenograft experiments demonstrated
      prolonged survival and increased 4HNE-modfied proteins in animals consuming a
      ketogenic diet combined with radiation compared to radiation alone. In the phase
      1 clinical trial, over a period of three years, seven NSCLC patients enrolled in
      the study. Of these, four were unable to comply with the diet and withdrew, two
      completed the study and one was withdrawn due to a dose-limiting toxicity. Over
      the same time period, two pancreatic cancer patients enrolled in the trial. Of
      these, one completed the study and the other was withdrawn due to a dose-limiting
      toxicity. The preclinical experiments demonstrate that a ketogenic diet increases
      radiation sensitivity in a pancreatic cancer xenograft model. However, patients
      with locally advanced NSCLC and pancreatic cancer receiving concurrent
      radiotherapy and chemotherapy had suboptimal compliance to the oral ketogenic
      diet and thus, poor tolerance.

PMID- 28437192
TI  - Phototoxicity of Vascular Endothelial Cells Caused by Contact with Talaporfin
      Sodium for 15-120 Min: In Vitro and In Vivo Studies.
AB  - OBJECTIVE: To reveal the mechanism of vascular patency in the myocardium after
      photosensitization immediately after talaporfin sodium (TS) injection in a canine
      model, we investigated acute injury to vascular endothelial cells (VECs) in vitro
      and in vivo. BACKGROUND DATA: There are many reports of vascular shutdown within
      the target region in photodynamic therapy with TS. Vascular patency within
      healthy canine myocardium in which a photosensitization reaction starts
      immediately after injection of TS has been reported. MATERIALS AND METHODS: TS
      fluorescence in human umbilical vein endothelial cells and cell lethality were
      measured with drug contact time (DCT) up to 120 min at 20 MUg/mL. Dependence of
      radiant exposure on cell lethality with 60 min DCT was investigated using two
      albumin concentrations that corresponded to those in plasma and interstices.
      Irradiation (21 mW/cm) outside the adventitia of canine cervical veins for 167 or
      667 sec was emitted through a diffuser probe 30 min after intravenous injection
      of TS (2.5 mg/kg). Veins were extracted ~30 min after the reaction and stained
      with von Willebrand factor. RESULTS: Intracellular fluorescence increased, but
      not cell lethality, with increasing DCT. Cell lethality increased gradually and
      reached 100% over 20 J/cm2 in the albumin concentration in the interstices.
      Normal VECs were found at the acute phase over 20 J/cm2 with a TS concentration
      in plasma of ~14 MUg/mL in vivo. CONCLUSIONS: VEC injury after a
      photosensitization reaction to healthy tissue shortly after TS injection might be
      low enough for the blood vessels to be patent.

PMID- 28437193
TI  - Evaluation of the Effects of Photobiomodulation on Biomechanical Properties and
      Hounsfield Unit of Partial Osteotomy Healing in an Experimental Rat Model of Type
      I Diabetes and Osteoporosis.
AB  - BACKGROUND: Pulsed wave (PW) lasers exhibit biostimulatory effects on fractures
      in healthy and diabetic animals. OBJECTIVE: This study aims to assess the effects
      of photobiomodulation on bone strength and Hounsfield unit (HU) for repair of a
      bone defect in an experimental rat model of type I diabetes mellitus (TIDM) and
      osteoporosis (OP). METHODS: We divided 30 female rats into six groups of n = 5
      per group: (1) ovariectomy (OVX) control, (2) OVX + PW laser and no TIDM, (3) OVX
      control + TIDM, (4) OVX + TIDM + PW laser, (5) OVX + TIDM + alendronate, and (6)
      OVX + TIDM + PW laser + alendronate. TIDM was induced in rats by streptozotocin
      (STZ). A partial osteotomy was made in the right tibia of each rat. We used an
      infrared laser (890 nm, 80 Hz, 1.5 J/cm2) 3 times per week. At 30 days after
      surgery, the callus areas within the rats' tibias were submitted to computed
      tomography scanning followed by the three-point bending test. RESULTS: The PW
      laser + alendronate group had significantly increased HU and biomechanical
      properties of repairing bone defect in STZ + OVX rats compared with the control
      groups. CONCLUSIONS: Combined treatment of PW laser and alendronate significantly
      enhanced bone repair in an experimental model rat of TIDM and OP.

PMID- 28437194
TI  - Comparison of Three Final Irrigation Activation Techniques: Effects on Canal
      Cleanness, Smear Layer Removal, and Dentinal Tubule Penetration of Two Root Canal
      Sealers.
AB  - OBJECTIVE: The aim of this study was to compare three final irrigation activation
      techniques with respect to their effects on debridement efficacy, smear layer
      removal, and dentinal tubule penetration of two different root canal sealers.
      BACKGROUND DATA: Different applications to improve the delivery of irrigating
      solutions within the root canal system are currently being investigated, as not
      all of the mechanisms and effects of these techniques have been clearly
      identified. MATERIALS AND METHODS: One hundred forty-two single-rooted teeth were
      randomly divided into a control group and three experimental groups based on the
      irrigant activation technique used: EndoVac (EV) system, photon-induced
      photoacoustic streaming (PIPS), and conventional syringe irrigation (CSI).
      Thirteen specimens from each experimental group were evaluated for debris and
      smear layer removal using scanning electron microscopy. The remaining 30
      specimens per group were divided into two subgroups according to the root canal
      sealer used: AH Plus and TotalFill BC. The maximum depth and total percentage of
      sealer penetration were measured using confocal laser scanning microscopy.
      RESULTS: PIPS resulted in significantly less debris in the middle third of the
      root canal compared with CSI (p < 0.01). There were no significant differences
      among CSI, EV, and PIPS concerning debris removal at coronal and apical levels or
      smear layer removal at all levels (p > 0.05). TotalFill BC use after final
      irrigation with EV and CSI at 2 mm or PIPS at 5 mm exhibited a significantly
      higher percentage of sealer penetration than that with AH Plus (p < 0.05). When
      AH Plus was used, PIPS allowed deeper sealer penetration than CSI at 2 mm (p <
      0.05). CONCLUSIONS: The effects of EV, PIPS, and CSI on debridement efficacy,
      smear layer removal, and dentinal tubule penetration were almost comparable.
      TotalFill BC showed superior tubular penetration than AH Plus.

PMID- 28437195
TI  - Home Health Chains and Practice Patterns: Evidence of 2008 Medicare Reimbursement
      Revision.
AB  - Home health agencies (HHAs) are known to exploit the Medicare reimbursement
      schedule by targeting a specific number of therapy visits. These targeting
      behaviors cause unnecessary medical spending. The Centers for Medicare & Medicaid
      Services estimates that during fiscal year 2015, Medicare made more than $10
      billion in improper payments to HHAs. Better understanding of heterogeneous
      gaming behaviors among HHAs can inform policy makers to more effectively oversee
      the home health care industry. This article aims to study how home health chains
      adjust and adopt new targeting behaviors as compared to independent agencies
      under the new reimbursement schedule. The analytic data are constructed from: (1)
      5% randomly sampled Medicare home health claim data, and (2) HHA chain
      information extracted from the Medicare Cost Report. The study period spans from
      2007 to 2010, and the sample includes 7800 unique HHAs and 380,118 treatment
      episodes. A multivariate regression model is used to determine whether chain and
      independent agencies change their practice patterns and adopt different targeting
      strategies after the revision of the reimbursement schedule in 2008. This study
      finds that independent agencies are more likely to target 6 and 14 visits, while
      chain agencies are more likely to target 20 visits. Such a change of practice
      patterns is more significant among for-profit HHAs. The authors expect these
      findings to inform policy makers that organizational structures, especially the
      combination of for-profit status and chain affiliation, should be taken into the
      consideration when detecting medical fraud and designing the reimbursement
      schedule.

PMID- 28437196
TI  - Surgical Site Infection and Colorectal Surgical Procedures: A Prospective
      Analysis of Risk Factors.
AB  - BACKGROUND: Colorectal surgical procedures (CRS) are associated with the highest
      surgical site infection (SSI) rate among elective operations. A wide range of
      patient and surgical characteristics have been identified as risk factors for
      SSI. Most studies are limited by reliance on retrospective data or subset
      analysis of data that includes CRS. This study reflects analysis of SSI risk
      factors using prospectively collected data in an elective CRS population.
      PATIENTS AND METHODS: We analyzed data prospectively collected as part of a
      randomized, blinded trial of skin anti-sepsis in elective CRS to identify risk
      factors associated with SSI, including superficial or deep SSI or cellulitis
      within 30 days post-discharge. Photodocumentation, patient questionnaires, and
      blinded review by an attending surgeon were used to identify SSI. Multi-variable
      logistic regression was used to identify factors significantly associated with
      SSI and to calculate predicted risks of SSI. RESULTS: From 2011 to 2015, 787
      patients undergoing clean-contaminated procedures by colorectal surgeons were
      analyzed as part of a randomized clinical trial. The overall SSI rate was 21.5%.
      Four variables-incision length, surgical indication, body mass index, and
      surgical approach-were significantly associated with SSI. Based on these four
      variables, the predicted risk of SSI ranges from <5% to >60%. CONCLUSION: This
      study represents the largest prospective investigation of SSI in elective CRS.
      There is a very wide range of SSI risk after CRS based on both modifiable and non
      modifiable factors. Identification of those at the extreme ends of risk may help
      us both identify and mitigate contributors to infection.

PMID- 28437197
TI  - Pressure Irrigation of Surgical Incisions and Traumatic Wounds.
AB  - BACKGROUND: Pressure irrigation of surgical incisions and traumatic wounds is
      commonly used to prevent infections. Commercial pressure irrigation devices have
      proliferated rapidly, but scientific validation of clinical benefit or
      appropriate use remains uncertain. METHODS: The published experimental and
      clinical investigations of pressure irrigation have been reviewed since the
      introduction of the Waterpik device in 1967 to identify the evidence for use to
      prevent soft tissue infections associated with injury wounds or surgical
      incisions. RESULTS: The published literature favors low pressure irrigation
      between 5-15 pounds/square inch (psi) for experimental removal of bacteria from
      contaminated tissues, with pressures higher being associated with soft tissue and
      bone injury. No experimental or clinical data have demonstrated improved benefit
      from pulsed over continuous lavage. Clinical studies have been very heterogeneous
      in patient populations and study design; meta-analysis was not feasible. High
      risk abdominal operations may have lower surgical site infection rates with
      pressure irrigation. Pressure irrigation in fractures and joint replacement
      surgery has shown mixed results. The largest multi-center randomized trial showed
      no benefit of pulsed (8-10 psi) lavage over conventional continuous gravity
      irrigation of open fractures. CONCLUSIONS: Experimental studies have shown
      effective removal of bacteria and contamination, but with a potential risk of
      tissue injury or displacement of contamination deeper into the soft tissues.
      Rigorous clinical documentation has not validated the optimum flow or pressure
      characteristics of pressure lavage in clinical practice. There is need for
      randomized clinical trials to validate pressure lavage in the prevention of
      infections in soft tissue injuries or high-risk surgical incisions.

PMID- 28437198
TI  - Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of
      Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance.
AB  - BACKGROUND: Branched chain amino acids (BCAA) may be involved in the pathogenesis
      of insulin resistance and are associated with type 2 diabetes mellitus (T2DM)
      development. Adipokines such as leptin and adiponectin influence insulin
      resistance and reflect adipocyte dysfunction. We examined the extent to which the
      association of BCAA with insulin resistance is attributable to altered leptin and
      adiponectin levels in individuals with varying degrees of glucose tolerance.
      METHODS: BCAA were measured by nuclear magnetic resonance, whereas leptin and
      adiponectin were measured by immunoassay, in subjects with normal fasting glucose
      (n = 30), impaired fasting glucose (n = 25), and T2DM (n = 15). Insulin
      resistance was estimated by homeostasis model assessment (HOMAir). RESULTS: BCAA
      were higher in men than in women (P < 0.001) and tended to be higher in T2DM
      subjects (P = 0.10) compared to subjects with normal or impaired fasting glucose.
      In univariate regression analysis, BCAA were correlated with HOMAir (r = 0.46; P
      < 0.001) and inversely with adiponectin (r = -0.53; P < 0.001) but not with
      leptin (r = -0.08; P > 0.05). Multivariable linear regression analysis, adjusting
      for age, sex, T2DM, and body mass index (BMI), demonstrated that BCAA were
      positively associated with HOMAir (beta = 0.242, P = 0.023). When BCAA, leptin,
      and adiponectin were included together, the positive relationship of HOMAir with
      BCAA (beta = 0.275, P = 0.012) remained significant. CONCLUSIONS: Insulin
      resistance was associated with BCAA. This association remained after adjusting
      for age, sex, T2DM, BMI, as well as leptin and adiponectin. It is unlikely that
      the relationship of insulin resistance with BCAA is to a major extent
      attributable to effects of leptin and adiponectin.

PMID- 28437199
TI  - The Correlation of Arterial Stiffness with Biophysical Parameters and Blood
      Biochemistry.
AB  - INTRODUCTION: Type 2 diabetes presents with numerous macrovascular and
      microvascular impairments, which in turn lead to various co-morbidities. Vascular
      co-morbidities can be seen when examining arterial stiffness (AS), which is a
      predictor for endothelial health and cardiovascular disease risk. Pulse wave
      analysis (PWA) and pulse wave velocity (PWV) are two tests that are commonly used
      to measure AS. Currently, disease states and progression are tracked via blood
      biochemistry. These gold standards in monitoring diabetes are expensive and need
      optimization. RESEARCH QUESTION: To investigate which biophysical and biochemical
      parameters correlated best with AS, which may reduce the number of biochemical
      tests and biophysical parameter measurements needed to track disease progression.
      METHODS: Data from 42 subjects with type 2 diabetes mellitus for <=10 years, aged
      40-70 years, were analyzed at a single time point. We investigated various blood
      biochemistry, body composition, and AS parameters. RESULTS: A combination of fat
      mass and fat-free mass was most associated with PWA over any other parameters.
      Leptin and high-sensitivity C-reactive protein seem to be the next two parameters
      that correlate with augmentation index. No other parameters had strong
      correlations to either PWA or PWV values. CONCLUSIONS: Body composition methods
      seemed to be better predictors of type 2 diabetes mellitus patient's vascular
      disease progression. Our study indicates that body composition measurements may
      help replace expensive tests. This may have public health and health surveillance
      implications in countries facing financial challenges.

PMID- 28437200
TI  - Effects of Dietary Macronutrient Composition on FNDC5 and Irisin in Mice Skeletal
      Muscle.
AB  - BACKGROUND: Fibronectin type III domain containing 5 (FNDC5) and its protein
      product Irisin are therapeutic targets for obesity-associated disorders. Irisin
      plays an important role in energy regulation, inducing browning of white
      adipocytes, and improving obesity. We aimed to investigate the association
      between muscle Irisin expression and dietary quality. METHODS: Twenty-eight
      female mice were divided into four groups and fed the following experimental
      diets for 60 days: standard diet (SD), high-carbohydrate diet (HCD), high-fat
      diet (HFD), and high-protein diet (HPD). We evaluated body weight, food intake,
      serum total cholesterol, triacylglycerol, and glucose. We also performed glucose
      tolerance and insulin sensitivity tests. Expression of FNDC5 was evaluated by
      quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR)
      of soleus muscle. Western blot was used to assess Irisin protein expression.
      RESULTS: The major finding of the present study was that HFD and HCD were
      associated with a downregulation of FNDC5. In addition to these results, we noted
      a significant reduction in skeletal muscle Irisin level. HPD prevented reductions
      of both FNDC5 and Irisin levels, as well as increased brown adipose tissue,
      compared to the control group. CONCLUSIONS: In conclusion, we observed that the
      HPD type of diet can change both FNDC5 expression and Irisin levels. Thus, the
      HPD might be the most appropriate diet to achieve high amounts of Irisin, a
      target molecule for the treatment of obesity and its co-morbidities.

PMID- 28437201
TI  - The Impact of Community-Based Palliative Care on Utilization and Cost of Acute
      Care Hospital Services in the Last Year of Life.
AB  - BACKGROUND: Community-based palliative care may potentially benefit patients by
      offering their preferred care at the end of life and benefit systems by reducing
      hospital use. OBJECTIVE: To compare place of death and acute care hospital use in
      the last year of life between cancer decedents who did and did not access a
      community-based palliative care service (PCS). DESIGN: Retrospective
      observational cohort study using linked individual administrative records from
      cancer registry, hospital, emergency department (ED), mortality, and PCS
      databases. Propensity score-weighted regression methods were used.
      SETTING/SUBJECTS: Whole of population study incorporating 28,561 West Australian
      cancer decedents from 2001 to 2011. MEASUREMENTS: Exposure was defined as
      ever/never accessed PCS. Outcomes were place of death (in/out of hospital) and
      the number, length of stay, and cumulative cost of hospital admissions at the end
      of life. RESULTS: Decedents who accessed the service (n = 16,530) had triple
      (adjusted odds ratio 3.19 [3.01-3.38]) the odds of dying out of hospital compared
      with those who did not. Unplanned hospitalizations were reduced in the last year
      (adjusted incidence rate ratio [IRR] 0.94 [0.91-0.97]) and last week of life
      (adjusted [IRR] 0.35 [0.33-0.38]), as were ED presentations (adjusted RR 0.92
      [0.98-0.95], adjusted RR 0.26 [0.23-0.28]) in the last year and last week of
      life, respectively. There were significant reductions in average total bed days (
      7.60 [-8.34 to -6.87]) and acute care costs (-A$5,491 [-A$6,155 to -A$4,827])
      over the last year of life. CONCLUSIONS: In addition to supporting people to die
      out of hospital, PCS was associated with reduced acute care admissions, bed days,
      and costs over the last year of life. The provision of high-quality palliative
      care in the community alleviates the burden on acute care hospitals and, thus,
      may partially offset public funding of this model.

PMID- 28437202
TI  - Low-Dose Morphine for Dyspnea in Terminally Ill Patients with Idiopathic
      Interstitial Pneumonias.
AB  - BACKGROUND: Dyspnea is highly prevalent in patients with idiopathic interstitial
      pneumonias (IIPs). OBJECTIVE: The objective of this study is to examine the
      effectiveness and safety of continuous subcutaneous morphine for dyspnea in
      terminally ill IIP patients. SETTING/SUBJECTS: We retrospectively reviewed cases
      of terminally ill IIP patients who received continuous subcutaneous morphine for
      dyspnea. MEASUREMENTS: We reviewed dyspnea severity measured using numerical
      rating scale (NRS) and respiratory rate (RR) before and two and four hours after
      morphine initiation. We conducted subgroup analyses of patients with and without
      noninvasive positive pressure ventilation (NPPV). RESULTS: Twenty-five patients
      were included in this study. Median morphine dose at morphine initiation and two
      and four hours after treatment was 0.25, 0.25, and 0.5 mg/hour, respectively.
      Dyspnea NRS decreased significantly four hours after (mean +/- standard
      deviation: 5.32 +/- 2.58, p = 0.04) but not two hours (5.52 +/- 2.43, p = 0.11)
      after morphine initiation compared with baseline (7.08 +/- 2.33). RR did not
      change significantly either two or four hours after treatment compared with
      baseline. The median survival after morphine initiation was 47 hours. Patients
      who were not using NPPV showed significantly improved dyspnea both two and four
      hours after treatment compared with baseline, although patients who used NPPV
      showed no significant improvement with morphine. RR did not significantly change
      in either subgroup. CONCLUSIONS: Morphine might improve dyspnea in terminally ill
      IIP patients without decrease in RR.

PMID- 28437203
TI  - Using the Surprise Question To Identify Those with Unmet Palliative Care Needs in
      Emergency and Inpatient Settings: What Do Clinicians Think?
AB  - BACKGROUND: The surprise question (SQ), "Would you be surprised if this patient
      died within the next year?" is effective in identifying end-stage renal disease
      and cancer patients at high risk of death and therefore potentially unmet
      palliative care needs. Following implementation of the SQ in our acute care
      setting, we sought to explore hospital-based providers' perceptions of the tool.
      OBJECTIVES: To evaluate (1) providers' perceptions regarding the feasibility of
      SQ use in emergency and inpatient settings, (2) clinician perceptions regarding
      the utility of the SQ, and (3) barriers to SQ use. DESIGN: A cross-sectional
      survey of medical providers following addition of the SQ to the electronic record
      for all patients admitted to a tertiary care hospital. RESULTS: A total of
      111/203 (55%) providers participated: 48/57 (84%) emergency physicians (EPs) and
      63/146 (43%) inpatient providers (IPs). Most reported no difficulty using the SQ.
      Modest numbers in both groups reported that the SQ influenced care delivery (EPs
      37%, IPs 42%) as well as goals of care (EPs 45%, IPs 52%). At least some advance
      care planning discussions were prompted by the SQ (EPs 45%, IPs 58%). Team
      discussions were influenced by SQ use for more than half of each group. Most
      respondents (55%) expressed some concern that their SQ responses could be
      inaccurate. CONCLUSIONS: In this setting, clinicians indicated that use of the SQ
      is feasible, acceptable, and useful in facilitating advance care planning
      discussions among teams, patients, and families. Many reported that SQ use
      influenced goals of care, but concern regarding accuracy was a barrier.
      Additional research examining SQ accuracy and predictive ability is warranted.

PMID- 28437204
TI  - Drainage Percutaneous Endoscopic Gastrostomy for Malignant Bowel Obstruction in
      Gastrointestinal Cancers: Prognosis and Implications for Timing of Palliative
      Intervention.
AB  - BACKGROUND: Malignant bowel obstruction (MBO) is a frequent complication in
      patients with advanced solid tumors. Palliative relief may be achieved by the use
      of a drainage percutaneous endoscopic gastrostomy (dPEG) tube, although optimal
      timing of placement remains unknown. OBJECTIVES: To determine median survival
      after diagnosis of MBO and dPEG placement, factors associated with worse survival
      in MBO, factors associated with receipt of dPEG, and association of timing of
      dPEG placement on survival. METHODS: This observational retrospective cohort
      study examined 439 patients with MBO on a gastrointestinal medical oncology
      inpatient service. Patients were characterized by age, gender, race, primary
      cancer type, length of stay, readmission, complications (aspiration pneumonia or
      bowel perforation), and receipt of dPEG. Select factors were analyzed to examine
      overall survival (OS) and dPEG placement. RESULTS: Median survival from diagnosis
      of first MBO was 2.5 months. Median survival after dPEG placement was 37 days. In
      univariate analysis, dPEG placement, complications, longer length of stay, and
      readmissions were significantly associated with worse OS. Receipt of dPEG was
      significantly associated with younger age, longer length of stay at first
      admission, and shorter interval to readmission. In patients who received dPEG,
      longer interval from MBO diagnosis to dPEG placement did not affect OS.
      CONCLUSION: We found that prognosis following diagnosis of MBO in patients with
      gastrointestinal malignancies remains poor. Our data suggest that timing of dPEG
      placement in MBO does not affect OS and, therefore, earlier intervention with
      this procedure may allow earlier and prolonged palliative relief.

PMID- 28437205
TI  - "She Would Be Flailing Around Distressed": The Critical Role of Home-Based
      Palliative Care for Patients with Advanced Cancer.
AB  - BACKGROUND: Patients with advanced cancer experience significant symptoms,
      ineffective treatments, and hospice underutilization. Home-based palliative care
      (HBPC) may fill a service gap for patients who require intensive home management,
      but are not enrolled in hospice. Even as data emerge on the utilization impacts
      of HBPC, other impacts are not as well known. METHODS: We describe findings of a
      pilot project in HBPC, Community Bridges (CB), for patients with advanced cancer.
      We assessed baseline symptom severity, caregiver burden, patient and caregiver
      program satisfaction, and CB team experience. RESULTS: Seventeen patients were
      seen. Baseline patient symptom burden and caregiver burden were high. Half of
      patients died within six months of enrollment. Patients and caregivers reported
      high program satisfaction and that CBs filled a gap in care. CB providers often
      served in the role as crisis managers and as trusted reporters for treating
      oncologists. CONCLUSIONS: CBs filled an unmet need for patients with advanced,
      metastatic cancer who desired ongoing cancer treatment, but were also in need of
      intensive end-of-life home services.

PMID- 28437206
TI  - Life-Threatening Illness and a Mother's Emotional Journey: Lessons in Care.

PMID- 28437207
TI  - Persistent Delirium in Chronic Critical Illness as a Prodrome Syndrome before
      Death.
AB  - BACKGROUND: Chronic critical illness (CCI) patients have poor functional
      outcomes, high risk of mortality, and significant sequelae, including delirium
      and cognitive dysfunction. The prognostic significance of persistent delirium in
      patients with CCI has not been well described. OBJECTIVE: We report a case of a
      patient with CCI following major cardiac surgery who was hemodynamically stable
      following a long course in the cardiothoracic intensive care unit (CTICU), but
      had persistent and unremitting delirium. Despite both pharmacological and
      nonpharmacological approaches to improve his delirium, the patient ultimately
      continued to have symptoms of delirium and subsequently died in the CTICU.
      Efforts to reconsider the goals of care, given his family's understanding of his
      values, were met with resistance as his cardiothoracic surgeon believed that he
      had a reasonable chance of recovery since his organs were not in failure. This
      case description raises the question of whether we should consider persistent
      delirium as a prodrome syndrome before death in patients with CCI. DESIGN: Study
      and analysis of a case of a patient with CCI following major cardiothoracic
      surgery who was hemodynamically stable with persistent delirium. CONCLUSIONS:
      Further studies of the prevalence and outcomes of prolonged or persistent
      agitated delirium in patients with chronic critical illness are needed to provide
      prognostic information that can assist patients and families in receiving care
      that accords with their goals and values.

PMID- 28437208
TI  - Considerations for Quality Improvement in Radiation Oncology Therapy for Patients
      with Uncomplicated Painful Bone Metastases.
AB  - BACKGROUND: There is an increasing need for evidence-based efficiency in
      providing a growing amount of cancer care. One example of a quality gap is the
      use of multiple-fraction palliative radiation for patients with advanced cancer
      who have uncomplicated bone metastases; evidence suggests similar pain outcomes
      for treatment regimens with a lower burden of treatments. METHODS: During the
      first phase of quality improvement work, we used RAND/UCLA appropriateness
      methodology to understand how radiation oncologists at one academic medical
      center rate the appropriateness of different treatment regimens for painful
      uncomplicated bone metastases. We compared radiation oncologist appropriateness
      ratings for radiation treatments with radiation therapy provided by these
      oncologists to patients with painful bone metastases between July 2012 and June
      2013. RESULTS: Appropriateness ratings showed that single-fraction (8 Gy)
      treatment (a low burden treatment) was consistently considered an appropriate
      option to treat a variety of uncomplicated bone metastases. The use of >10
      fractions was consistently rated as inappropriate regardless of other factors.
      Eighty-one patients receiving radiation therapy for painful bone metastases
      during the study period had an available medical record for chart abstraction.
      Almost one-third of metastases were considered complicated because of a concern
      of spinal cord compression, a history of prior irradiation, or an associated
      pathological fracture. Among uncomplicated bone metastases, 25% were treated with
      stereotactic body radiation treatment (SBRT). Among the 54 uncomplicated bone
      metastases treated with conformal radiation, only one was treated with single
      fraction treatment and 32% were treated with greater than 10 fractions.
      CONCLUSIONS: Treatment at the study site demonstrates room for improvement in
      providing low-burden radiation oncology treatments for patients with painful bone
      metastases. Choosing a radiation treatment schedule for patients with advanced
      cancer and painful bone metastases requires consideration of many medical and
      patient-centered factors. Our experience suggests that it will take more than the
      existence of guidelines to change practice in this area.

PMID- 28437209
TI  - Conversations About Goals and Values Are Feasible and Acceptable in Long-Term
      Acute Care Hospitals: A Pilot Study.
AB  - RATIONALE: The chronically critically ill have survived acute critical illness
      but require prolonged mechanical ventilation. These patients are frequently
      transferred from acute care to long-term acute care hospitals (LTACHs) for
      prolonged recovery, yet many suffer setbacks requiring readmission to acute care.
      The patient's relatively improved condition while at the LTACH might be an
      opportunity for communication regarding care goals; however, there have been no
      prior studies of the feasibility of such conversations in the LTACH. OBJECTIVES:
      To determine the feasibility, acceptability, and potential usefulness of
      conversations about serious illness with chronic critical illness patients or
      their surrogate decision makers after LTACH admission. METHODS: We adapted an
      existing conversation guide for use in chronically critically ill (defined by
      tracheotomy for prolonged ventilation) LTACH patients or their surrogates to
      explore views about quality of life, understanding of medical conditions,
      expectations, and planning for setbacks. These conversations were conducted by
      one interviewer and summarized for the patients' clinicians. We surveyed
      patients, surrogates, and clinicians to assess acceptability. MEASUREMENT AND
      MAIN RESULTS: A total of 70 subjects were approached and 50 (71%) were enrolled,
      including 30 patients and 20 surrogates. The median duration of the conversation
      was 14 minutes 45 seconds [IQR 12:46, 19]. The presence of ongoing mechanical
      ventilation did not lead to longer conversations; in fact, conversations with
      patients were shorter than those with surrogates. The majority of subjects (81%)
      described the conversation as worthwhile. The majority of clinicians (73%)
      reported that the conversation offered a new and significant understanding of the
      patient's preferences if a setback were to occur. CONCLUSIONS: Conversations
      about serious illness care goals can be accomplished in a relatively short period
      of time, are acceptable to chronically critically ill patients and their
      surrogate decision makers in the LTACH, and are perceived as worthwhile by
      patients, surrogates, and clinicians.

PMID- 28437211
TI  - International Association for Hospice and Palliative Care Endorses Volitional
      Death by Starvation and Dehydration.

PMID- 28437210
TI  - Factors Associated with Length of Stay at Home in the Final Month of Life among
      Advanced Cancer Patients: A Retrospective Chart Review.
AB  - BACKGROUND: Living at home is an important factor for maintaining high quality of
      life among patients. Many studies have discussed parameters associated with place
      of death, but no studies have yet clarified which factors influence the length of
      stay at home during the end of life. OBJECTIVE: The aim of this study was to
      identify factors influencing the amount of time spent at home during the final
      month of life among patients with advanced cancer. METHODS: A retrospective chart
      review was conducted for 415 patients with advanced cancer. Multivariate multiple
      linear regression analysis was used to examine relationships between the length
      of stay at home during the final month of life and variables measuring patient's
      background (four indicators), family structure (three indicators) cancer type
      (four types), chief complaint at initial palliative care referral (seven
      indicators), and medical interventions (three factors). RESULTS: The multiple
      linear regression predicting time spent at home in the last month of life yielded
      partial regression coefficients of 4.2 for past outpatient palliative care
      services (OPCS) (p < 0.001) and 3.3 for in-home nurse visits (p = 0.003).
      DISCUSSION: The most influential factor for length of stay at home in the final
      month of life was a history of OPCS. Many patients with advanced cancer who
      receive chemotherapy without OPCS spend time as inpatients after an initial
      period at home. Palliative care interventions for outpatients effectively enable
      patients with advanced cancer to adapt and continue living at home.

PMID- 28437212
TI  - The Impact of Communication Skills Training on Cardiology Fellows' and Attending
      Physicians' Perceived Comfort with Difficult Conversations.
AB  - BACKGROUND: Cardiologists need to decide which treatments are appropriate for
      seriously ill patients and whether they align with patient goals. Reconciling
      medical options with patients' wishes requires skilled communication. Although
      there is evidence that communication is teachable, few cardiologists receive
      formal training. OBJECTIVE: To demonstrate that providing communication skills
      training to cardiologists is feasible and improves their perceived preparedness
      (PP) for leading difficult conversations. METHODS: CardioTalk is a workshop to
      improve communication through short didactic sessions followed by interactions
      with standardized patients. Competencies include giving bad news, defining goals
      of care, responding to emotion, supporting religious beliefs, and withdrawing
      therapies. Settings/Subjects: First year cardiology fellows, heart failure
      fellows, and cardiac intensive care unit attendings. MEASUREMENTS: Surveys
      evaluated the curriculum's efficacy and learners' PP before and after the
      workshop. RESULTS: Eight cardiology attendings and 20 cardiology fellows
      participated. Eighty-nine percent reported having any prior education in
      communication. Fellows reported more prior education than attendings (100% vs.
      62.5%, p = 0.017). Level of PP improved in all competencies for all learners.
      Ninety-six percent of respondents would recommend the training to peers. All
      attendings felt that it should be required for cardiologists in the cardiac
      intensive care unit and reported improved preparedness to teach communication to
      learners. CONCLUSION: All learners improved in levels of PP in communication
      competencies. CardioTalk is the first described training program that prepares
      cardiologists for the challenges they face when having conversations with
      seriously ill patients.

PMID- 28437213
TI  - Current Status and Challenges of Three-Dimensional Modeling and Printing of
      Tissues and Organs.

PMID- 28437214
TI  - Speaker Introductions at Internal Medicine Grand Rounds: Forms of Address Reveal
      Gender Bias.
AB  - BACKGROUND: Gender bias has been identified as one of the drivers of gender
      disparity in academic medicine. Bias may be reinforced by gender subordinating
      language or differential use of formality in forms of address. Professional
      titles may influence the perceived expertise and authority of the referenced
      individual. The objective of this study is to examine how professional titles
      were used in the same and mixed-gender speaker introductions at Internal Medicine
      Grand Rounds (IMGR). METHODS: A retrospective observational study of video
      archived speaker introductions at consecutive IMGR was conducted at two different
      locations (Arizona, Minnesota) of an academic medical center. Introducers and
      speakers at IMGR were physician and scientist peers holding MD, PhD, or MD/PhD
      degrees. The primary outcome was whether or not a speaker's professional title
      was used during the first form of address during speaker introductions at IMGR.
      As secondary outcomes, we evaluated whether or not the speakers professional
      title was used in any form of address during the introduction. RESULTS: Three
      hundred twenty-one forms of address were analyzed. Female introducers were more
      likely to use professional titles when introducing any speaker during the first
      form of address compared with male introducers (96.2% [102/106] vs. 65.6%
      [141/215]; p < 0.001). Female dyads utilized formal titles during the first form
      of address 97.8% (45/46) compared with male dyads who utilized a formal title
      72.4% (110/152) of the time (p = 0.007). In mixed-gender dyads, where the
      introducer was female and speaker male, formal titles were used 95.0% (57/60) of
      the time. Male introducers of female speakers utilized professional titles 49.2%
      (31/63) of the time (p < 0.001). CONCLUSION: In this study, women introduced by
      men at IMGR were less likely to be addressed by professional title than were men
      introduced by men. Differential formality in speaker introductions may amplify
      isolation, marginalization, and professional discomfiture expressed by women
      faculty in academic medicine.

PMID- 28437215
TI  - Contraceptive Use and Pregnancy Incidence Among Women Participating in an HIV
      Prevention Trial.
AB  - BACKGROUND: Recent HIV prevention trials required use of effective contraceptive
      methods to fulfill eligibility for enrollment. We compared pregnancy rates in a
      subset of participants enrolled in the Microbicide Trials Network protocol (MTN
      003), a randomized trial of chemoprophylaxis to prevent HIV acquisition among
      women aged 18-45 years who initiated depot medroxyprogesterone acetate (DMPA) or
      combined oral contraceptives (COCs) at enrollment, relative to those already
      using DMPA or COCs. METHODS: Data were analyzed from MTN-003 participants from
      Uganda. Before enrollment, information on contraceptive type and initiation date
      was obtained. Urine pregnancy tests were performed at monthly follow-up visits.
      Cox proportional hazards models were used to compare pregnancy incidence among
      new users (initiated <=60 days before enrollment) and established users
      (initiated >60 days before enrollment). RESULTS: Of 322 women enrolled, 296 were
      COC or DMPA users, 82 (28%) were new users, and 214 (72%) were established users.
      Pregnancy incidence was higher among new contraceptive users compared to
      established users (20.70% vs. 10.55%; adjusted hazard ratio [HR] = 1.66; 95%
      confidence interval [95% CI] 0.93-2.96). Among DMPA users, pregnancy incidence
      was 10.20% in new users versus 3.48% in established users (HR = 2.56; 95% CI 0.86
      7.65). Among new COC users, pregnancy incidence was 42.67% in new users versus
      23.67% in established COC users (adjusted HR = 1.74; 95% CI 0.87-3.48).
      CONCLUSIONS: New contraceptive users, regardless of method, at the Uganda MTN-003
      site had an increased pregnancy risk compared to established users, which may be
      due to contraceptive initiation primarily for trial eligibility. New users may
      benefit from intensive contraceptive counseling and additional contraceptive
      options, including longer acting reversible contraceptives.

PMID- 28437217
TI  - Fleeing the Ivory Tower: Gender Differences in the Turnover Experiences of Women
      Faculty.
AB  - PURPOSE: Prior research has established that women and men faculty have different
      experiences in their professional and personal lives and that academic turnover
      can be costly and disruptive to home institutions. However, relatively little
      research has examined gender differences in the antecedent events that
      contributed to faculty members' voluntary turnover decisions. This study aims to
      fill this gap. MATERIALS AND METHODS: Qualitative and quantitative data were
      obtained in two ways: by directly contacting faculty members who had voluntarily
      left their positions through the human resource departments at six institutions
      and through more wide-scale snowball sampling. The surveys, administered via
      paper or web based, measured the extent to which participants' experiences with
      harassment/discrimination, family-related issues, and recruitment/retention
      offers impacted their decisions to leave. Qualitative data were coded by raters
      into numerical values, and mean differences based on gender were assessed for
      these and the quantitative data. RESULTS: Both the qualitative and quantitative
      data suggest that female academicians reported experiencing significantly more
      gender-based harassment/discrimination, were much more likely to cite family
      related reasons for leaving, and reported receiving significantly fewer external
      job offers and internal retention offers than their male counterparts.
      CONCLUSIONS: Academic science departments should be keenly aware of and strive to
      reduce instances of harassment/discrimination against female academicians, offer
      more support for family-related issues and encourage faculty to take advantage of
      these programs, and conduct search and retention efforts fairly regardless of
      faculty gender.

PMID- 28437216
TI  - Posttraumatic Symptom Reporting and Reported Cigarette Smoking During Pregnancy.
AB  - INTRODUCTION: Increased prevalence of nicotine dependence among individuals
      suffering from posttraumatic stress disorder (PTSD) is well established. However,
      there are limited studies on the prevalence of smoking during pregnancy in
      relation to prepregnancy history of trauma exposures and active PTSD symptoms
      during pregnancy. Prenatal smoking has been implicated in a host of negative
      outcomes for mother and baby. Given maternal and fetal risk, it is critical to
      define predictors of continued cigarette smoking during pregnancy. METHODS:
      Pregnant women from an urban perinatal clinic completed an anonymous survey of
      trauma history using a modified Traumatic Life Events Questionnaire (TLEQ), PTSD
      symptoms using the PTSD Symptom Checklist-Civilian Version (PCL-C) and current
      and past smoking behavior. Those who smoked any number of cigarettes per day
      after pregnancy confirmation were considered to be "pregnant smokers." RESULTS:
      Of 218 women who completed the survey, 34 (15.6%) reported smoking cigarettes
      after confirmation of pregnancy. In unadjusted models, trauma exposure that
      resulted in fear, helplessness, or horror (FHH), as well as current PTSD symptom
      severity and probable PTSD diagnosis showed statistical significance as
      predictors of smoking during pregnancy. After adjusting for age only, PTSD
      symptoms retained their significant association with smoking during pregnancy.
      When history of smoking at least five cigarettes per day was added to our models,
      none of the associations remained significant. CONCLUSIONS: These findings
      emphasize the importance of the behavioral response to past traumatic exposures
      in influencing cigarette smoking behavior before pregnancy. Given such behaviors
      enhance risk for continued tobacco use during pregnancy, a trauma-informed
      approach to smoking cessation in preconception care may ultimately reduce the
      likelihood of smoking during pregnancy and requires further study.

PMID- 28437218
TI  - Patient, Physician, and Practice Characteristics Associated with Cardiovascular
      Disease Preventive Care for Women.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death for
      American women. Although CVD preventive care has the potential to reduce a
      significant number of these deaths, the degree to which healthcare providers
      deliver such care is unknown. The purpose of this study was to identify patient,
      physician, and practice characteristics that significantly influence the
      provision of CVD preventive care during ambulatory care visits for female
      patients. METHODS: The National Ambulatory Medical Care Survey datasets from 2005
      to 2010 were utilized. The study sample included female patients >=20 years of
      age whose healthcare provider performed CVD preventive care and who had visits
      for a new health problem, a routine chronic problem, management of a chronic
      condition, and preventive care. Binary logistic regression models estimated the
      association of patient, physician, and practice characteristics and CVD
      preventive care; cholesterol testing, body mass index (BMI) screening, and
      tobacco education. RESULTS: Of the 32,009 visits, 15.9% involved cholesterol
      testing, 50.3% involved BMI screening, and 3.20% involved tobacco education.
      Obstetricians/gynecologists were less likely to perform cholesterol testing (aOR:
      0.39; 95% CI: 0.25-0.61) and tobacco education (aOR: 0.56; 95% CI: 0.32-0.98)
      than general/family physicians. CONCLUSION: The delivery of CVD preventive care
      varied by healthcare provider type, with obstetricians/gynecologists having lower
      odds of providing two of the three services. The amount of time a physician spent
      with a patient was a significant predictor for the provision of all three
      services. These findings demonstrate the need to implement multifaceted
      approaches to address predicting characteristics of CVD preventive care.

PMID- 28437219
TI  - Factors Affecting Sexual Function in Midlife Women: Results from the Midlife
      Women's Health Study.
AB  - OBJECTIVE: The objective of this study was to estimate the importance of risk
      factors affecting sexual function in sexually active midlife women. MATERIALS AND
      METHODS: A cohort of 780 women undergoing the menopausal transition was surveyed
      each year for up to 7 years. Data were collected from sexually active women on
      sexual function, including frequencies of enjoyment, arousal, orgasm, passion for
      partner, satisfaction with partner, pain, lack of lubrication, fantasizing, and
      sexual activity. Data were also collected on a large number of potential risk
      factors for sexual dysfunction, including behaviors (smoking and alcohol use),
      health status (overall and frequency of different disorders), and demographic
      information (race, education, income, etc.). Height and weight were measured at
      an annual clinic visit; serum hormone concentrations were assayed using blood
      samples donated annually. Data on individual outcomes were examined with ordinal
      logistic regression models using individual as a random effect. An overall sexual
      function score was constructed from individual outcome responses, and this score
      was examined with linear regression. All factors with univariate associations of
      p < 0.1 were considered in multivariate model building with stepwise addition.
      RESULTS: A total of 1,927 women-years were included in the analysis. Women with
      much more physical work than average had higher sexual function scores and higher
      rates of enjoyment, passion, and satisfaction. Higher family income was
      associated with lower sexual function score and more frequent dry sex. Married
      women had significantly lower sexual function scores, as did those with frequent
      irritability or vaginal dryness. A higher step on the Ladder of Life was
      associated with a higher sexual function score and higher frequency of sexual
      activity. CONCLUSIONS: The factors associated with sexual outcome in menopausal
      women are complex and vary depending on the sexual outcome.

PMID- 28437220
TI  - Lean Mass and Fat Mass as Mediators of the Relationship Between Physical Activity
      and Bone Mineral Density in Postmenopausal Women.
AB  - BACKGROUND: The relationship between physical activity (PA) and bone health is
      well known, but the role of lean mass (LM) and fat mass (FM) in this relationship
      remains uncertain. Therefore, the aim of this study was to examine the mediating
      effect of LM and FM on the relationship between PA and bone mineral density (BMD)
      in postmenopausal women. MATERIALS AND METHODS: This cross-sectional study
      involved 282 postmenopausal women aged between 50 and 65 year, who were randomly
      selected from Hongqi community of Harbin City in China. PA was measured using an
      International PA Questionnaire. Body composition, BMD of the lumbar spine, hip,
      and total body were measured using dual-energy X-ray absorptiometry. Mediation
      analysis was performed to investigate the mediating effect of LM and FM on the
      relationship between PA and BMD. RESULTS: In partial correlation analysis, PA,
      LM, and FM were positively related to BMD. Positive correlation was found between
      PA and LM. There were significant differences in BMD between different categories
      of PA, but the differences disappeared after adjusting for LM. Mediation analysis
      showed that LM and FM played a mediating role in the relationship between PA and
      BMD. LM appeared to mediate the effect of BMD in the spine, hip, and total body
      by 26.91%, 19.55% and 47.98%, respectively; and FM was 22.23%, 27.97%, and
      33.02%, respectively. CONCLUSION: LM and FM affected the relationship between PA
      and BMD as mediator. Postmenopausal women with high LM and FM had more BMD.

PMID- 28437221
TI  - The Effect of Reinforcement Methods with Knotted and Knotless Sutures: Comparison
      of Burst Pressures.
AB  - Sleeve gastrectomy operations have become popular among restrictive obesity
      surgeons, due to its effectiveness for losing weight and acceptable complication
      rates. However, leakage is a significant problem in these operations. In this ex
      vivo study, we tried to understand mechanisms of leakage and to examine the
      effects of two different types of frequently referred reinforcement techniques
      using sutures. The resected gastric specimens that were removed during sleeve
      gastrectomy operations were used in this ex vivo study. Foley catheters were
      inserted to stomach from two different areas along the greater curvature of
      stomach, and one of these catheters was connected to monitoring apparatus with
      intra-abdominal pressure measurement system. The other Foley catheter was
      connected to syringe apparatus with 1000 cc physiological saline. No
      reinforcement procedure was applied to staple line in the first group. In the
      second group, staple line was sutured continuously with 2/0 knotless absorbable
      suturing material. In the third group, continuous suturing was applied using 2/0
      knotted absorbable sutures. Next, stomach was filled with physiological saline,
      and the site of leak and the pressure value at the level of leakage were noted.
      Pressure values that caused leakage in no reinforcement suture, knotless suture,
      and knotted suture groups were 42.7 (+/-1), 98.7 (+/- 3.9), and 97.7 (+/-4.1)
      mmHg, respectively. The pressure difference between the groups was statistically
      significant (P = .000). As for the site of leaks, 26 (58%) were in corpus, 14
      (31%) were in antrum, and 5 (11%) were in fundus, and there was no significant
      difference between the groups in terms of leakage sites (P = .97). In sleeve
      gastrectomy operations, reinforcement of staple line using either knotless or
      knotted sutures may help to prevent leakage.

PMID- 28437222
TI  - Laparoscopic Anatomical Segment 2 Segmentectomy by the Glissonian Approach.
AB  - BACKGROUND: When hepatocellular carcinoma (HCC) was located in segment 2 (S2),
      segment-oriented hepatectomy was more beneficial than left lateral sectionectomy
      as this type of anatomical resection preserved the volume of the nontumor-bearing
      segment. Herein, we presented 2 cases (1 with video) of laparoscopic anatomical
      S2 segmentectomy by the Glissonian approach. METHODS: The first patient was a 69
      year-old woman, who had an incidentally detected liver nodule on abdominal
      ultrasound for systemic surveillance for her breast cancer. The preoperative
      liver function was Child-Pugh class A. Abdominal computed tomography showed a 2
      cm low attenuating lesion in S2. Contrast magnetic resonance imaging (MRI) showed
      the same lesion with features more suggestive of HCC. In view of the inconclusive
      imaging findings, a needle biopsy was performed and it confirmed the diagnosis of
      HCC. The second patient was a 57-year-old man with hepatitis B and Child-Pugh
      class B liver cirrhosis. He had an enlarging nonenhancing liver nodule in S2
      noted on MRI. Laparoscopic anatomical S2 segmentectomy was performed for these 2
      patients. RESULTS: The operative time for the first and second patients was 240
      and 185 minutes, respectively. The respective estimated intraoperative blood loss
      was 50 and 250 mL and no transfusion was necessary. The patients were discharged
      on the fourth and fifth postoperative day without any complications,
      respectively. CONCLUSION: This study showed the feasibility of performing a
      laparoscopic S2 segmentectomy by the Glissonian approach.

PMID- 28437223
TI  - Exercise and Peripheral Nerve Grafts as a Strategy To Promote Regeneration after
      Acute or Chronic Spinal Cord Injury.
AB  - Therapeutic interventions after spinal cord injury (SCI) routinely are designed
      to address multiple aspects of the primary and/or secondary damage that occurs.
      Exercise has a demonstrated efficacy for post-SCI complications such as
      cardiovascular dysfunction, neuropathic pain, and chronic inflammation, yet there
      is little understanding of the mechanisms by which improvements might result from
      this non-invasive approach. Here we review several of our observations of
      molecular and cellular changes within the injured spinal cord following acute or
      delayed exercise regimens that illustrate the potential for positive effects on
      neuroprotection and rehabilitation. Further, we provide new information about the
      role of exercise in promoting the regeneration of spinal axons into peripheral
      nerve grafts (PNGs) placed immediately or 6 weeks after injury. Acute and
      chronically injured propriospinal neurons within the lumbar spinal cord displayed
      the greatest propensity for enhanced regeneration after exercise, which
      correlates with the direct sensory input to this region from exercised hindlimb
      muscles. Future studies will extend these observations by testing whether
      exercise will boost the regenerative effort of axons to extend beyond the graft,
      interact with intraspinal targets, and establish functional connections across a
      lesion.

PMID- 28437224
TI  - Structure, Process, and Culture of Intensive Care Units Treating Patients with
      Severe Traumatic Brain Injury: Survey of Centers Participating in the American
      College of Surgeons Trauma Quality Improvement Program.
AB  - Outcome after severe traumatic brain injury (TBI) differs substantially between
      hospitals. Explaining this variation begins with understanding the differences in
      structures and processes of care, particularly at intensive care units (ICUs)
      where acute TBI care takes place. We invited trauma medical directors (TMDs) from
      187 centers participating in the American College of Surgeons Trauma Quality
      Improvement Program (ACS TQIP) to complete a survey. The survey domains included
      ICU model, type, availability of specialized units, staff, training programs,
      standard protocols and order sets, approach to withdrawal of life support, and
      perceived level of neurosurgeons' engagement in the ICU management of TBI. One
      hundred forty-two TMDs (76%) completed the survey. Severe TBI patients are
      admitted to dedicated neurocritical care units in 52 hospitals (37%), trauma ICUs
      in 44 hospitals (31%), general ICUs in 34 hospitals (24%), and surgical ICUs in
      11 hospitals (8%). Fifty-seven percent are closed units. Board-certified
      intensivists directed 89% of ICUs, whereas 17% were led by neurointensivists.
      Sixty percent of ICU directors were general surgeons. Thirty-nine percent of
      hospitals had critical care fellowships and 11% had neurocritical care
      fellowships. Fifty-nine percent of ICUs had standard order sets and 61% had
      standard protocols specific for TBI, with the most common protocol relating to
      intracranial pressure management (53%). Only 43% of TMDs were satisfied with the
      current level of neurosurgeons' engagement in the ICU management of TBI; 46%
      believed that neurosurgeons should be more engaged; 11% believed they should be
      less engaged. In the largest survey of North American ICUs caring for TBI
      patients, there is substantial variation in the current approaches to ICU care
      for TBI, highlighting multiple opportunities for comparative effectiveness
      research.

PMID- 28437225
TI  - Neck Collar with Mild Jugular Vein Compression Ameliorates Brain Activation
      Changes during a Working Memory Task after a Season of High School Football.
AB  - Emerging evidence indicates that repetitive head impacts, even at a sub
      concussive level, may result in exacerbated or prolonged neurological deficits in
      athletes. This study aimed to: 1) quantify the effect of repetitive head impacts
      on the alteration of neuronal activity based on functional magnetic resonance
      imaging (fMRI) of working memory after a high school football season; and 2)
      determine whether a neck collar that applies mild jugular vein compression
      designed to reduce brain energy absorption in head impact through "slosh"
      mitigation can ameliorate the altered fMRI activation during a working memory
      task. Participants were recruited from local high school football teams with 27
      and 25 athletes assigned to the non-collar and collar group, respectively. A
      standard N-Back task was used to engage working memory in the fMRI at both pre-
      and post-season. The two study groups experienced similar head impact frequency
      and magnitude during the season (all p > 0.05). fMRI blood oxygen level dependent
      (BOLD) signal response (a reflection of the neuronal activity level) during the
      working memory task increased significantly from pre- to post-season in the non
      collar group (corrected p < 0.05), but not in the collar group. Areas displaying
      less activation change in the collar group (corrected p < 0.05) included the
      precuneus, inferior parietal cortex, and dorsal lateral prefrontal cortex.
      Additionally, BOLD response in the non-collar group increased significantly in
      direct association with the total number of impacts and total g-force (p < 0.05).
      Our data provide initial neuroimaging evidence for the effect of repetitive head
      impacts on the working memory related brain activity, as well as a potential
      protective effect that resulted from the use of the purported brain slosh
      reducing neck collar in contact sports.

PMID- 28437226
TI  - First Report of Prevalence of CTX-M-15-Producing Escherichia coli O25b/ST131 from
      Iran.
AB  - The emergence of Escherichia coli sequence type 131 (ST131) as a multidrug
      resistant and virulent pathogen represents a major challenge to public health
      globally. Recently, the O25b/ST131 E. coli producing CTX-M-15 with high virulence
      potential has been reported worldwide, but has received little attention in Iran.
      This study is the first in Iran to specifically determine the spread of the
      O25b/ST131 clone producing CTX-M-15 among E. coli isolates belonging to the B2
      phylogenetic group. ST131 clone in phylogenetic group B2 was detected based on
      PCR detection of ST131-specific single-nucleotide polymorphisms in mdh and gyrB.
      O25b/ST131 E. coli clone was confirmed utilizing O25b/ST131 clone allele-specific
      PCR for the pabB gene. All group B2 E. coli isolates were characterized based on
      antibiotic susceptibility, extended-spectrum beta-lactamase (ESBL) enzymes, and
      virulence traits. Our results demonstrated that 38 out of the 154 B2 group
      isolates (24.7%) were identified as belonging to the ST131 clone. Furthermore, of
      these, 28 isolates (73.6%) were detected as O25b/ST131 clone. Antibiotic
      resistance of ST131 E. coli isolates to ciprofloxacin, gentamicin, cefotaxime,
      and aztreonam was significantly higher than non-ST131 isolates. Almost all of the
      O25b/ST131 isolates with the ability for ESBL production were reported as CTX-M
      15 producing (95.5%). Our results showed that the most prevalent virulence trait
      in ST131 clone was ompT (94.7%). This study is the first to report the prevalence
      of the CTX-M-15-producing O25b/ST131 E. coli in Iran. Our findings reinforce the
      surveillance of dissemination of ST131 E. coli clone as a major drug-resistant
      pathogen and an important new public health threat.

PMID- 28437227
TI  - Emergence of the Uncommon Clone ST944/ST78 Carrying blaOXA-40-like and blaCTX-M
      like Genes Among Carbapenem-Nonsusceptible Acinetobacter baumannii in Moscow,
      Russia.
AB  - Carbapenem-nonsusceptible (Carba-NS) Acinetobacter baumannii has emerged as an
      important cause of nosocomial infections. In the present study, we characterized
      91 Carba-NS A. baumannii isolates collected from patients of surgical departments
      and intensive care units at three hospitals in Moscow in 2012-2015. Multilocus
      sequence typing (MLST) using the Oxford (Oxf) scheme identified 16 sequence types
      (STs) of three clonal complexes (CCs), including CC92Oxf (67%), CC109Oxf (1%),
      CC944Oxf (29%), and the singleton ST1100Oxf (3%). CC944Oxf was composed of
      ST944Oxf (n = 16) and two of its newly described single locus variants ST1103Oxf
      (n = 3) and ST1104Oxf (n = 7); all the three STs were identical to the Pasteur
      (Pas) MLST scheme ST78. All CC944Oxf/ST78Pas isolates were blaOXA-40-like
      positive and all but one isolate harbored a blaCTX-M-like gene. ST944Oxf was the
      only ST found in each of the three study hospitals. Biofilm growth capacity was
      similar among Carba-NS and nonclonal carbapenem-susceptible isolates. Our data
      demonstrate the predominance of two clonal lineages among Carba-NS A. baumannii.
      One of these, the uncommon blaOXA-40-like/blaCTX-M-like-positive clone of
      CC944Oxf/ST78Pas, seems to be endemic in Russia.

PMID- 28437228
TI  - First Case of NDM-1-Producing Klebsiella pneumoniae in Annaba University
      Hospital, Algeria.
AB  - AIM: The aim of this study was to characterize two carbapenem-resistant
      Klebsiella pneumoniae isolates recovered from urine samples in a patient
      hospitalized at Annaba University hospital (Algeria) in 2014. RESULTS: Two K.
      pneumoniae isolates were studied because they proved resistant to almost all
      antibiotics tested with a high level resistance to ertapenem (minimum inhibitory
      concentration = 32 mg/L). The results of modified Hodge test and combined disk
      test (ROSCO Diagnostica, Taastrup, Denmark) were positive. The two isolates
      harbored the blaNDM-1 gene and one was also positive for blaCTX-M-15. Screening
      of aminoglycoside-modifying enzymes and plasmid-mediated quinolone resistance
      contents detected aac(6')-Ib-cr, aac(3')-II, qnrB2, and oqxAB in both isolates.
      Multilocus sequence typing demonstrated that the two isolates belonged to
      sequence type 147. However, repetitive sequence-based PCR and pulsed-field gel
      electrophoresis showed that they were not clonally related. The blaNDM-1 gene and
      all other resistant genes were contained on an IncR plasmid of c.a. 85 kb.
      CONCLUSIONS: This study comprises the first identification of NDM-1-producing K.
      pneumoniae in Algeria. We thus confirm the concerning worldwide dissemination of
      this carbapenemase that involves the emergence of the IncR plasmid and the
      success of the ST147 clonal complex harboring it.

PMID- 28437229
TI  - Quinolone Resistance Determinants of Clinical Salmonella Enteritidis in Thailand.
AB  - Salmonella Enteritidis has emerged as a global concern regarding quinolone
      resistance and invasive potential. Although quinolone-resistant S. Enteritidis
      has been observed with high frequency in Thailand, information on the mechanism
      of resistance acquisition is limited. To elucidate the mechanism, a total of 158
      clinical isolates of nalidixic acid (NAL)-resistant S. Enteritidis were collected
      throughout Thailand, and the quinolone resistance determinants were investigated
      in the context of resistance levels to NAL, norfloxacin (NOR), and ciprofloxacin
      (CIP). The analysis of point mutations in type II topoisomerase genes and the
      detection of plasmid-mediated quinolone resistance genes showed that all but two
      harbored a gyrA mutation, the qnrS1 gene, or both. The most commonly affected
      codon in mutant gyrA was 87, followed by 83. Double codon mutation in gyrA was
      found in an isolate with high-level resistance to NAL, NOR, and CIP. A new
      mutation causing serine to isoleucine substitution at codon 83 was identified in
      eight isolates. In addition to eighteen qnrS1-carrying isolates showing
      nontypical quinolone resistance, one carrying both the qnrS1 gene and a gyrA
      mutation also showed a high level of resistance. Genotyping by multilocus
      variable number of tandem repeat analysis suggested a possible clonal expansion
      of NAL-resistant strains nationwide. Our data suggested that NAL-resistant
      isolates with single quinolone resistance determinant may potentially become
      fluoroquinolone resistant by acquiring secondary determinants. Restricted
      therapeutic and farming usage of quinolones is strongly recommended to prevent
      the emergence of fluoroquinolone-resistant isolates.

PMID- 28437230
TI  - High Diversity of Antimicrobial Resistance Genes, Class 1 Integrons, and
      Genotypes of Multidrug-Resistant Escherichia coli in Beef Carcasses.
AB  - Multidrug-resistant Escherichia coli can contaminate food meat during processing
      and cause human infection. Phenotypic and genotypic characterization of the
      antimicrobial resistance were conducted for 45 multidrug-resistant E. coli
      isolates from 208 samples of beef carcasses. The mechanisms of resistance were
      evaluated using polymerase chain reaction and sequencing methods, and the clonal
      relationship among isolates was evaluated using multilocus sequence typing (MLST)
      and pulsed-field gel electrophoresis (PFGE). Different variants of bla, tet, flo,
      dfrA, and aadA genes were detected in most of the strains resistant to beta
      lactam, tetracycline, chloramphenicol, sulfonamides, and aminoglycosides,
      respectively. Extended-spectrum beta-lactamase (ESBL)-producing E. coli was found
      in 42.2% of the 45 E. coli isolates and the most commonly detected ESBL genotypes
      were CTX-M group 1 and 9. Class 1 integrons with nine different arrangements of
      gene cassettes were present in 28 of 45 E. coli isolates. Twenty-nine PFGE groups
      and 24 MLST types were identified in their clonal structure. This study revealed
      that E. coli isolates from beef contained high diversity of antimicrobial
      resistance genes, integrons, and genotypes. These results highlighted the role of
      beef meat as a potential source for multidrug-resistant E. coli strains and the
      need for controlling beef safety.

PMID- 28437231
TI  - Capsular Polysaccharide Types and Virulence-Related Traits of Epidemic KPC
      Producing Klebsiella pneumoniae Isolates in a Chinese University Hospital.
AB  - Klebsiella pneumoniae is an important human pathogen associated with a variety of
      diseases and the prevalence of blaKPC carrying K. pneumoniae (KPC-Kp) is rapidly
      increasing. Capsule is an important virulence factor in K. pneumoniae. In this
      study, we determined to first systematically characterize capsular polysaccharide
      (CPS) and virulence traits in KPC-Kp strains. A total of 56 KPC-Kp isolates were
      recovered from clinical samples in a Chinese hospital, which were assigned to
      clonal lineages by multilocus sequence typing (MLST). Capsule typing (wzi
      sequencing and wzc polymerase chain reaction [PCR]) and virulence genes were
      characterized by molecular approaches. The virulence of these strains was
      determined by biofilm formation, serum killing resistance, phagocytosis, and
      infection models. Six different STs were found among 56 KPC-Kp isolates: 76.8%
      (43 of 56 isolates) belonged to ST11, 6 isolates belonged to ST147, 4 isolates
      belonged to ST15, 1 isolate belonged to ST1456, 1 isolate belonged to ST65, and 1
      isolate was ST23. Based on the wzi gene DNA sequences and wzc PCR, these 56
      strains were classified as capsular type wzi47-K47 (n = 37), wzi64-K64 (n = 8),
      wzi8-K8 (n = 4), wzi37-K37 (n = 4), wzi53-K53 (n = 1), wzi125-K2 (n = 1), and
      wzi1-K1 (n = 1). Heterogeneity was detected in biofilm formation and phagocytosis
      among different CPS types. ST11 strains were less virulent than other ST strains.
      KPC-Kp strains exhibit variability of virulence-associated traits. Differences
      were associated with the ST types and CPS.

PMID- 28437232
TI  - Epidemiological, Physiological, and Molecular Characteristics of a Brazilian
      Collection of Carbapenem-Resistant Acinetobacter baumannii and Pseudomonas
      aeruginosa.
AB  - Nonfermenting Gram-negative bacteria such as Pseudomonas aeruginosa and
      Acinetobacter baumannii are widespread in the environment and are increasingly
      associated with nosocomial infections, often associated with multidrug-resistance
      phenotypes. This study aimed to evaluate epidemiological, physiological, and
      molecular characteristics of carbapenem resistance in P. aeruginosa and A.
      baumannii. In total, 63 nonreplicated strains (44 A. baumannii and 19 P.
      aeruginosa) were isolated from hospitalized patients. Antimicrobial resistance
      patterns, biocide tolerance, oxidative stress, hemolytic activity, and biofilm
      formation were assessed. Genetic markers related to beta-lactamase synthesis,
      efflux systems, and porin loss were screened by PCR. Epidemiological data of
      patients were analyzed. Advanced age, intensive care unit admission, invasive
      medical devices, treatment with fluoroquinolones or beta-lactams/beta-lactamase
      inhibitor combinations, and prolonged hospital stay were predisposing factors for
      infection. Colistin showed to be active in vitro against these bacteria.
      Carbapenem-resistant P. aeruginosa strains did not show hemolytic activity and
      were less tolerant to oxidative stress and biocides. However, increased ability
      of biofilm formation was observed, comparing to the carbapenem-susceptible
      isolates. Genetic markers related to oxacillinases synthesis (OXA-23 and OXA
      143), oprD absence, and efflux pump (adeB) were detected in carbapenem-resistant
      A. baumannii. Screening for OXA-51-like gene was performed as confirmatory test
      for A. baumannii identification. In P. aeruginosa genes encoding efflux pumps
      (MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM) and SPM-1 were found;
      besides, oprD absence was also observed. Our results suggest that these organisms
      are well adapted to different environments and confirm the difficulty of
      therapeutic management of patients with infections associated with multidrug
      resistant microorganisms, with direct impact on mortality and epidemiological
      control of these strains in health centers.

PMID- 28437233
TI  - In Vitro Activity of Various Antibiotics in Combination with Tigecycline Against
      Acinetobacter baumannii: A Systematic Review and Meta-Analysis.
AB  - Given that tigecycline-based combination therapy is recognized as a valuable
      option for the treatment of tigecycline-resistant Acinetobacter baumannii, we
      conducted this systematic review and meta-analysis to assess the overall evidence
      of its effectiveness. The synergy rate was defined as the primary outcome that
      was calculated separately for time-kill, Etest, and checkerboard microdilution
      methods. The secondary outcomes were bactericidal activity and the efficacy of
      combination treatment on the development of resistance. In total, 37 published
      papers and 16 conference proceedings were included. Nine classes consisting of 22
      antibiotic types in combination with tigecycline against 1,159 A. baumannii
      strains were reported in the analysis. For the time-kill studies, combination
      therapy showed a synergy rate of 37.9% (95% confidence interval [CI], 30.7-46.5);
      the highest synergy rate was 67.4% (95% CI, 27.3-91.9) for tigecycline in
      combination with colistin. Moreover, combination with amikacin or colistin could
      efficiently inhibit the development of tigecycline resistance. Compared with
      checkerboard microdilution and Etest methods, time-kill studies always showed
      higher synergy rates. Altogether, these results suggest that the in vitro
      tigecycline-based combinations resulted in moderate synergy rates and that
      several combinations could suppress the resistance of A. baumannii to
      tigecycline, which should be further confirmed in animal models and clinical
      trials.

PMID- 28437234
TI  - Poliovirus vaccination during the endgame: insights from integrated modeling.
AB  - INTRODUCTION: Managing the polio endgame requires access to sufficient quantities
      of poliovirus vaccines. After oral poliovirus vaccine (OPV) cessation, outbreaks
      may occur that require outbreak response using monovalent OPV (mOPV) and/or
      inactivated poliovirus vaccine. Areas covered: We review the experience and
      challenges with managing vaccine supplies in the context of the polio endgame.
      Building on models that explored polio endgame risks and the potential mOPV needs
      to stop outbreaks from live poliovirus reintroductions, we conceptually explore
      the potential demands for finished and bulk mOPV doses from a stockpile in the
      context of limited shelf-life of finished vaccine and time delays to convert bulk
      to finished vaccine. Our analysis suggests that the required size of the mOPV
      stockpile varies by serotype, with the highest expected needs for serotype 1
      mOPV. Based on realizations of poliovirus risks after OPV cessation, the
      stockpile required to eliminate the chance of a stock-out appears considerably
      larger than the currently planned mOPV stockpiles. Expert commentary: The total
      required stockpile size depends on the acceptable probability of a stock-out, and
      increases with longer times to finish bulk doses and shorter shelf-lives of
      finished doses. Successful polio endgame management will require careful
      attention to poliovirus vaccine supplies.

PMID- 28437235
TI  - Breast Augmentation and Reconstruction from a Regenerative Medicine Point of
      View: State of the Art and Future Perspectives.
AB  - Breast reconstruction and augmentation are very common procedures, yet the
      prevailing current methods utilize silicone implants that may have significant
      local complications requiring reoperation. Lipofillling is increasingly used to
      contour and is considered safe, however, its utility is limited by significant
      volume loss. A new approach could offer an alternative and increase the scope of
      patient choice. A small number of teams around the world are investigating a
      breast tissue engineering (TE) paradigm. Conventional breast TE concepts are
      based on seeding a scaffold with the patients' own stem cells. However, the
      clinical viability of many of these approaches is limited by their costs in
      relevant volumes. In this article the state of the art of tissue-engineered
      breast reconstruction is reviewed and future perspectives are presented and
      discussed.

PMID- 28437236
TI  - Temperature Variation After Rewarming from Deep Hypothermic Circulatory Arrest Is
      Associated with Survival and Neurologic Outcome.
AB  - Therapeutic hypothermia is recommended by international guidelines after cardio
      circulatory arrest. However, the effects of different temperatures during the
      first 24 hours after deep hypothermic circulatory arrest (DHCA) for aortic arch
      surgery on survival and neurologic outcome are undefined. We hypothesize that
      temperature variation after aortic arch surgery is associated with survival and
      neurologic outcome. In the period 2010-2014, a total of 210 consecutive patients
      undergoing aortic arch surgery with DHCA were included. They were retrospectively
      divided into three groups by median nasopharyngeal temperature within 24 hours
      after rewarming: hypothermia (<36 degrees C; n = 65), normothermia (36-37 degrees
      C; n = 110), and hyperthermia (>37 degrees C; n = 35). Multivariate stepwise
      logistic and linear regressions were performed to determine whether different
      temperature independently predicted 30-day mortality, stroke incidence, and
      neurologic outcome assessed by cerebral performance category (CPC) at hospital
      discharge. Compared with normothermia, hyperthermia was independently associated
      with a higher risk of 30-day mortality (28.6% vs. 10.9%; odds ratio [OR] 2.8; 95%
      confidence interval [CI], 1.1-8.6; p = 0.005), stroke incidence (64.3% vs. 9.1%;
      OR 9.1; 95% CI, 2.7-23.0; p = 0.001), and poor neurologic outcome (CPC 3-5)
      (68.8% vs. 39.6%; OR 4.8; 95% CI, 1.4-8.7; p = 0.01). No significant differences
      were demonstrated between hypothermia and normothermia. Postoperative hypothermia
      is not associated with a better outcome after aortic arch surgery with DHCA.
      However, postoperative hyperthermia (>37 degrees C) is associated with high
      stroke incidence, poor neurologic outcome, and increased 30-day mortality. Target
      temperature management in the first 24 hours after surgery should be evaluated in
      prospective randomized trials.

PMID- 28437237
TI  - Proteomics in Hypothermia as Adjunctive Therapy in Patients with ST-Segment
      Elevation Myocardial Infarction: A CHILL-MI Substudy.
AB  - Cardiovascular and inflammatory biomarkers in therapeutic hypothermia have been
      studied in cardiac arrest, but data on patients with ST-segment elevation
      myocardial infarction (STEMI) treated with therapeutic hypothermia are currently
      unavailable. A multiplex proximity extension assay allowed us to measure 157
      cardiovascular disease (CVD) and inflammatory disease-related biomarkers in
      patients from the international, multicenter, and randomized trial; CHILL
      myocardial infarction (MI) and to explore the associations of cardiovascular and
      inflammatory biomarkers. Blood samples were obtained from 119 patients with
      STEMI, randomized to hypothermia as adjunctive therapy to percutaneous coronary
      intervention (PCI) or standard care with PCI only. Blood samples were obtained at
      baseline (0 hour), 6, 24, and 96 hours post PCI, and stored at -80 degrees C
      until they were analyzed by PROSEEK Multiplex CVD and PROSEEK Multiplex INF
      (Olink Bioscience, Uppsala, Sweden). Peak values from 6, 24, and 96 hours
      postrandomization were compared between treatment groups. One hundred fifty-seven
      cardiovascular and inflammatory biomarkers were evaluated. Peak values of four
      biomarkers (BDNF, DNER, CCL20, MMP3) were reduced in the hypothermia group as
      compared with the control group. In addition, seven markers were slightly
      elevated in the hypothermia group (OPG, FGF21, FS, IL12B, PRL, TIM, IL6). In a
      prespecified subgroup analysis of anterior infarctions, two additional markers
      were reduced (PTX3 and SELE). In this explorative proteomic study from the
      randomized trial CHILL-MI, four biomarkers were identified as having reduced peak
      plasma values in patients with STEMI treated with therapeutic hypothermia as
      adjunctive therapy to PCI as compared with patients treated with standard care of
      PCI. In addition, seven biomarkers were elevated in the group treated with
      hypothermia therapy. The effect of hypothermia on biomarker peak values was
      modest, possibly due to a low reduction in mean body temperature. Whether a
      faster and deeper cooling results in more pronounced effects is yet to be
      established.

PMID- 28437238
TI  - Selected Health Conditions Among Native Hawaiian and Pacific Islander Adults:
      United States, 2014.
AB  - KEY FINDINGS: Although the Asian or Pacific Islander federal race category was
      split into two in 1997 (1), few reliable health statistics are available for the
      Native Hawaiian and Pacific Islander (NHPI) population. In 2014, the National
      Center for Health Statistics (NCHS) fielded a first-of-its-kind federal survey
      focused exclusively on NHPI population health. This report uses data from that
      survey, in combination with 2014 data from the annual National Health Interview
      Survey (NHIS), to highlight differences in the prevalence of selected health
      conditions between the NHPI population and the Asian population with whom they
      have historically been combined.

PMID- 28437239
TI  - TPrevalence of HPV in Adults Aged 18-69: United States, 2011-2014.
AB  - KEY FINDINGS: Data from the National Health and Nutrition Examination Survey ?
      During 2011-2014, prevalence of any oral human papillomavirus (HPV) for adults
      aged 18-69 was 7.3%; high-risk HPV was 4.0%. ? Overall, prevalence of any and
      high-risk oral HPV was lowest among non-Hispanic Asian adults; any oral HPV was
      highest among non-Hispanic black adults. ? Prevalence of any and high-risk oral
      HPV was higher in men than women except for high-risk HPV among Asian adults. ?
      During 2013-2014, prevalence of any and high-risk genital HPV for adults aged 18
      59 was 45.2% and 25.1% in men and 39.9% and 20.4% in women, respectively. ?
      Prevalence of any and high-risk genital HPV was lower among non-Hispanic Asian
      and higher among non-Hispanic black than both non-Hispanic white and Hispanic men
      and women. Human papillomavirus (HPV) is the most common sexually transmitted
      infection in the United States (1). Some HPV types can cause genital warts and
      are considered low risk, with a small chance for causing cancer. Other types are
      considered high risk, causing cancer in different areas of the body including the
      cervix and vagina in women, penis in men, and anus and oropharynx in both men and
      women (2). This report provides the most recent national estimates of oral HPV
      prevalence among adults aged 18-69 from the National Health and Nutrition
      Examination Survey (NHANES) 2011-2014, as well as prevalence of genital HPV among
      adults aged 18-59 from NHANES 2013-2014. Estimates of any HPV (37 types tested)
      as well as high-risk HPV (14 of the 37 types) are provided.

PMID- 28437240
TI  - Trends in Infant Mortality in the United States, 2005-2014.
AB  - KEY FINDINGS: Infant mortality is considered a basic measure of public health for
      countries around the world (1-3). Over the past decade, the overall infant
      mortality rate in the United States has improved, declining 15% from 6.86 infant
      deaths per 1,000 live births in 2005-a recent high-to 5.82 in 2014 (4). Over the
      years, many efforts have been made to understand and lower infant mortality
      (4,5). This report examines the 2014 linked birth/infant death data from the
      National Vital Statistics System (NVSS) to describe trends in infant mortality in
      the United States by race and Hispanic origin, state, and leading causes of
      infant deaths from 2005 through 2014.

PMID- 28437241
TI  - United States Life Tables, 2013.
AB  - Objectives-This report presents complete period life tables for the United States
      by race, Hispanic origin, and sex, based on agespecific death rates in 2013.
      Methods-Data used to prepare the 2013 life tables are 2013 final mortality
      statistics; July 1, 2013 population estimates based on the 2010 decennial census;
      and 2013 Medicare data for persons aged 66-99. The methodology used to estimate
      the 2013 life tables was first implemented with data year 2008. The methodology
      used to estimate the life tables for the Hispanic population remains unchanged
      from that developed for the publication of life tables by Hispanic origin for
      data year 2006. Results-In 2013, the overall expectation of life at birth was
      78.8 years, unchanged from 2012. Between 2012 and 2013, life expectancy at birth
      remained the same for both males (76.4) and females (81.2), for the black
      population (75.5), the Hispanic population (81.9), and the non-Hispanic black
      population (75.1). Life expectancy at birth declined for both the white
      population (79.1 to 79.0) and the non-Hispanic white population (78.9 to 78.8).

PMID- 28437242
TI  - Anthropometric Reference Data for Children and Adults: United States, 2011-2014.
AB  - Anthropometry or human body measurements provide important indicators of
      nutritional status in children and adults (1). In children, measurements reflect
      general health status, dietary adequacy, and growth and development over time. In
      adults, body measurements are used to evaluate health and dietary status, disease
      risk, and body composition. This report presents anthropometric reference data
      for 2011-2014 for U.S. children and adults.

PMID- 28437243
TI  - Impact of pulmonary hypertension on in-hospital outcome after surgical or
      transcatheter aortic valve replacement.
AB  - AIMS: We aimed to analyse the impact of pulmonary hypertension (PH) on the in
      hospital outcome of either surgical aortic valve replacement (SAVR) or
      transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Data from all
      107,057 patients undergoing isolated SAVR or TAVR in Germany between 2007 and
      2014 were provided by the German Federal Bureau of Statistics. About 18% of
      patients with aortic valve stenosis suffered from PH. Patients with PH had more
      comorbidities with consequently increased EuroSCORE (TAVR without PH: 12.3%; with
      PH: 24%). The presence of PH led to an increase of in-hospital strokes,
      bleedings, acute kidney injuries, and pacemaker implantations in both treatment
      groups (TAVR and SAVR), but the PH-associated increase of complications and
      mortality was less pronounced among patients receiving TAVR (mortality after TAVR
      without PH: 5.4%; with PH: 7.2%). After baseline risk adjustment, the TAVR
      procedure was associated with a reduced risk of in-hospital stroke (OR 0.81,
      p=0.011), bleeding (OR 0.22, p<0.001), and mortality (OR 0.70, p=0.005) among PH
      patients, and in comparison to surgical treatment. CONCLUSIONS: PH is a risk
      factor for worse outcome of SAVR and TAVR. This fact is less pronounced among
      TAVR patients. Our data suggest a shift towards the transcatheter approach in
      patients suffering from PH.

PMID- 28437244
TI  - Second transcatheter closure for residual shunt following percutaneous closure of
      patent foramen ovale.
AB  - AIMS: Residual shunt following percutaneous patent foramen ovale (PFO) closure
      has been described in up to 49% of patients and is associated with recurrent
      cerebrovascular events. Our aim was to evaluate the safety, feasibility, and
      midterm outcomes of transcatheter residual shunt closure. METHODS AND RESULTS:
      From 1994 to July 2016, 2,679 patients underwent transcatheter PFO closure for
      treatment of presumed paradoxical embolism at our institution. Among them, 100
      patients (3.7%) were referred for residual shunt closure. They constituted the
      study population for which a retrospective analysis of the prospectively gathered
      procedural data was performed along with prospective acquisition of follow-up
      data. The indication for initial PFO closure was an ischaemic cerebrovascular
      event in 85% of the patients. Patients underwent transoesophageal
      echocardiography (TOE) for PFO diagnosis and again for residual shunt assessment
      at about six months. All procedures were performed under fluoroscopic guidance
      only. At the first procedure, 10 different devices had been used. The AMPLATZER
      PFO Occluder accounted for 54% and the AMPLATZER Cribriform Occluder for 28%.
      Compared to the whole population (n=2,679), a significantly higher rate of atrial
      septal aneurysm (58% versus 36%; p=0.024), a larger proportion of shunt grade 3
      at baseline (97% versus 78%; p<0.001), and a larger size (>=30 mm) of the first
      implanted device (47% versus 13%; p<0.001) were observed in the patients with
      residual shunt. Six patients (6%) experienced a recurrent TIA or ischaemic stroke
      before the second intervention. Residual shunt closure was successful in all but
      two patients. A second AMPLATZER PFO Occluder was used in the majority of the
      repeat interventions (76%). There were no complications. TOE, obtained again
      after 7+/-5 months in 88 of the 98 patients with a device in place (90%), showed
      complete closure in 81%. In eight patients (0.3% of the whole cohort), a third
      device was implanted, resulting in complete closure in all. CONCLUSIONS:
      Transcatheter residual shunt closure after initial percutaneous PFO closure can
      be safely performed under fluoroscopic guidance only and achieves complete
      closure in most patients. The use of larger devices, typically prompted by
      intricate anatomy, represents a risk factor for shunt persistence and the need
      for reintervention.

PMID- 28437245
TI  - Long-term outcome of a spontaneous coronary artery dissection treated with a
      bioresorbable scaffold.

PMID- 28437246
TI  - Emerging problem in medical education: ancillary staff and order sets.

PMID- 28437247
TI  - Does the location of a narrative comment section affect feedback on a lecture
      evaluation form?

PMID- 28437248
TI  - Protective effect of calretinin on testicular Leydig cells via the inhibition of
      apoptosis.
AB  - The core mechanism of Late-onset hypogonadism (LOH) is the deficiency of androgen
      due to the functional and quantitative decline of testicular Leydig cells. Here
      we explored the protective effect of calretinin, a Ca2+-binding protein, on
      Leydig cells. We found in MLTC-1 cells transfected with LV-calb2, the cell
      viability and optical density (OD) were higher (p<0.05), cells in the S phase of
      the cell cycle were increased (p<0.01) and p-ERK1/2 and p-AKT levels were
      significantly higher (p<0.01 and p<0.05), while in R2C cells transfected with LV
      siRNA-calb2, all of the results mentioned above were adverse (p<0.05). The cell
      apoptotic index after calretinin over-expressed was significantly lower
      (p<0.001), while the expression levels of mitochondria-related apoptotic factors
      such as cleaved caspase-9 and cytochrome C (cyto C) were lower and ratio of
      Bcl2/Bax was higher (p<0.05). After calretinin down-regulated, the apoptotic
      index was higher (p<0.05), while the expression levels of mitochondria-related
      apoptotic factors were higher and the ratio of Bcl2/Bax was lower (p<0.05).
      Therefore, calretinin increases Leydig cell viability and proliferation, possibly
      via ERK1/2 and AKT pathways, and suppresses apoptosis possibly via the
      mitochondria-related apoptotic pathway, which could be beneficial in
      understanding the pathophysiology of LOH and could lead to the study of new
      treatments.

PMID- 28437249
TI  - The differential spatiotemporal expression pattern of shelterin genes throughout
      lifespan.
AB  - Shelterin forms the core complex of telomere proteins and plays critical roles in
      protecting telomeres against unwanted activation of the DNA damage response and
      in Emaintaining telomere length homeostasis. Although shelterin expression is
      believed to be ubiquitous for stabilization of chromosomal ends. Evidences
      suggest that some shelterin subunits have tissue-specific functions. However,
      very little is known regarding how shelterin subunit gene expression is regulated
      during development and aging. Using two different animal models, the mouse and
      zebrafish, we reveal herein that shelterin subunits exhibit distinct spatial and
      temporal expression patterns that do not correlate with the proliferative status
      of the organ systems examined. Together, this work shows that the shelterin
      subunits exhibit distinct spatiotemporal expression patterns, suggesting
      important tissue-specific functions during development and aging.

PMID- 28437251
TI  - Solution processible MoOx-incorporated graphene anode for efficient polymer light
      emitting diodes.
AB  - Graphene has attracted great attention owing to its superb properties as an anode
      of organic or polymer light-emitting diodes (OLEDs or PLEDs). However, there are
      still barriers for graphene to replace existing indium tin oxide (ITO) due to
      relatively high sheet resistance and work function mismatch. In this study, PLEDs
      using molybdenum oxide (MoOx) nanoparticle-doped graphene are demonstrated on a
      plastic substrate to have a low sheet resistance and high work function. Also,
      this work shows how the doping amount influences the electronic properties of the
      graphene anode and the PLED performance. A facile and scalable spin coating
      process was used for doping graphene with MoOx. After doping, the sheet
      resistance and the optical transmittance of five-layer graphene were ~180 Omega
      sq-1 and ~88%, respectively. Moreover, the surface roughness of MoOx-doped
      graphene becomes smoother than that of pristine graphene. Furthermore, a
      nonlinear relationship was observed between the MoOx doping level and device
      performance. Therefore, a modified stacking structure of graphene electrode is
      presented to further enhance device performance. The maximum external quantum
      efficiency (EQE) and power efficiency of the PLED using the MoOx-doped graphene
      anode were 4.7% and 13.3 lm W-1, respectively. The MoOx-doped graphene anode
      showed enhanced device performance (261% for maximum EQE, 255% for maximum power
      efficiency) compared with the pristine graphene.

PMID- 28437252
TI  - Valley filtering in graphene due to substrate-induced mass potential.
AB  - The interaction of monolayer graphene with specific substrates may break its
      sublattice symmetry and results in unidirectional chiral states with opposite
      group velocities in the different Dirac cones (Zarenia et al 2012 Phys. Rev. B 86
      085451). Taking advantage of this feature, we propose a valley filter based on a
      transversal mass kink for low energy electrons in graphene, which is obtained by
      assuming a defect region in the substrate that provides a change in the sign of
      the substrate-induced mass and thus creates a non-biased channel, perpendicular
      to the kink, for electron motion. By solving the time-dependent Schrodinger
      equation for the tight-binding Hamiltonian, we investigate the time evolution of
      a Gaussian wave packet propagating through such a system and obtain the transport
      properties of this graphene-based substrate-induced quantum point contact. Our
      results demonstrate that efficient valley filtering can be obtained, provided:
      (i) the electron energy is sufficiently low, i.e. with electrons belonging mostly
      to the lowest sub-band of the channel, and (ii) the channel length (width) is
      sufficiently long (narrow). Moreover, even though the transmission probabilities
      for each valley are significantly affected by impurities and defects in the
      channel region, the valley polarization in this system is shown to be robust
      against their presence.

PMID- 28437253
TI  - Charge transfer driven emergent phenomena in oxide heterostructures.
AB  - Complex oxides exhibit many intriguing phenomena, including metal-insulator
      transition, ferroelectricity/multiferroicity, colossal magnetoresistance and high
      transition temperature superconductivity. Advances in epitaxial thin film growth
      techniques enable us to combine different complex oxides with atomic precision
      and form an oxide heterostructure. Recent theoretical and experimental work has
      shown that charge transfer across oxide interfaces generally occurs and leads to
      a great diversity of emergent interfacial properties which are not exhibited by
      bulk constituents. In this report, we review mechanisms and physical consequence
      of charge transfer across interfaces in oxide heterostructures. Both theoretical
      proposals and experimental measurements of various oxide heterostructures are
      discussed and compared. We also review the theoretical methods that are used to
      calculate charge transfer across oxide interfaces and discuss the success and
      challenges in theory. Finally, we present a summary and perspectives for future
      research.

PMID- 28437250
TI  - Ionizing radiation reduces ADAM10 expression in brain microvascular endothelial
      cells undergoing stress-induced senescence.
AB  - Cellular senescence is associated with aging and is considered a potential
      contributor to age-associated neurodegenerative disease. Exposure to ionizing
      radiation increases the risk of developing premature neurovascular degeneration
      and dementia but also induces premature senescence. As cells of the
      cerebrovascular endothelium are particularly susceptible to radiation and play an
      important role in brain homeostasis, we investigated radiation-induced senescence
      in brain microvascular endothelial cells (EC). Using biotinylation to label
      surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the
      surface proteome of stress-induced senescent EC in culture. An array of both
      recognized and novel senescence-associated proteins were identified. Most
      notably, we identified and validated the novel radiation-stimulated down
      regulation of the protease, a disintegrin and metalloprotease 10 (ADAM10). ADAM10
      is an important modulator of amyloid beta protein production, accumulation of
      which is central to the pathologies of Alzheimer's disease and cerebral amyloid
      angiopathy. Concurrently, we identified and validated increased surface
      expression of ADAM10 proteolytic targets with roles in neural proliferation and
      survival, inflammation and immune activation (L1CAM, NEO1, NEST, TLR2, DDX58).
      ADAM10 may be a key molecule linking radiation, senescence and endothelial
      dysfunction with increased risk of premature neurodegenerative diseases normally
      associated with aging.

PMID- 28437254
TI  - Interaction-driven distinctive electronic states of artificial atoms at the ZnO
      interface.
AB  - We have investigated the electronic states of planar quantum dots at the ZnO
      interface containing a few interacting electrons in an externally applied
      magnetic field. The electron-electron interaction effects are expected to be much
      stronger in this case than in traditional semiconductor quantum systems, such as
      in GaAs or InAs quantum dots. In order to highlight that stronger Coulomb effects
      in the ZnO quantum dots, we have compared the energy spectra and the
      magnetization in this system to those of the InAs quantum dots. We have found
      that in the ZnO quantum dots the signatures of stronger Coulomb interaction
      manifests in an unique ground state that has very different properties than the
      corresponding ones in the InAs dot. Our results for the magnetization also
      exhibits behaviors never before observed in a quantum dot for a realistic set of
      parameters. We have found a stronger temperature dependence and other unexpected
      features, such as paramagnetic-like behavior at high temperatures for a quantum
      dot helium.

PMID- 28437255
TI  - Capped carbon nanotubes with a number of ground state magnetization
      discontinuities increasing with their size.
AB  - The classical ground state magnetic response of fullerene molecules that resemble
      capped carbon nanotubes is calculated within the framework of the
      antiferromagnetic Heisenberg model. It is found that the magnetic response
      depends subtly on spatial symmetry and chirality. Clusters based on armchair
      carbon nanotubes which are capped with non-neighboring pentagons and have D 5d
      spatial symmetry have a number of magnetization discontinuities which increases
      with their size. This occurs even though the model completely lacks magnetic
      anisotropy, and even though the only source of frustration are the two groups of
      six pentagons located at the ends of the molecules, which become more strongly
      outnumbered as the clusters are filled in the middle with more unfrustrated
      hexagons with increasing size. For the cluster with 180 vertices there are
      already seven magnetization and one susceptibility discontinuities. Contrary to
      that, similar molecules which have D 5h spatial symmetry reach a limit of one
      magnetization and two susceptibility ground state discontinuities, while
      fullerene molecules based on zigzag carbon nanotubes and capped by neighboring
      pentagons also reach a fixed number of discontinuities with increasing size.

PMID- 28437256
TI  - Electron inelastic mean free path at energies below 100 eV.
AB  - Knowledge of electron inelastic mean free paths (IMFPs) is important for electron
      spectroscopy and microscopy studies. Here, we determine the IMFPs at energies
      below 100 eV for 10 elemental solids (V, Fe, Ni, Mo, Pd, Ag, Ta, W, Pt, and Au)
      within the dielectric formalism, using the energy-loss function calculated in the
      adiabatic local-density approximation of time-dependent density-functional
      theory. The resulting IMFPs at a few eV above the Fermi energy are comparable to
      those from ab initio calculations in the GW approximation of many-body theory.
      The present approach provides an alternative to evaluate hot-electron inelastic
      lifetimes.

PMID- 28437257
TI  - Creation of quasi-Dirac points in the Floquet band structure of bilayer graphene.
AB  - We study the Floquet quasi-energy band structure of bilayer graphene when it is
      illuminated by two laser lights with frequencies [Formula: see text] and
      [Formula: see text] using Floquet theory. We focus on the dynamical gap formed by
      the conduction band with Floquet index  =  -1 and the valence band with Floquet
      index  =  +1 to understand how Dirac points can be formed. It is found that the
      dynamical gap does not have rotation symmetry in the momentum space, and quasi
      Dirac points, where the conduction and valence bands almost touch, can be created
      when the dynamical gap closes along some directions with suitably chosen
      radiation parameters. We derive analytical expressions for the direction
      dependence of the dynamical gaps using Lowdin perturbation theory to gain a
      better understanding of the formation of quasi-Dirac points. When both radiations
      are circularly polarized, the gap can be exactly zero along some directions, when
      only the first and second order perturbations are considered. Higher order
      perturbations can open a very small gap in this case. When both radiations are
      linearly polarized, the gap can be exactly zero up to the fourth order
      perturbation and more than one quasi-Dirac point is formed. We also study the
      electron velocity around a dynamical gap and show that the magnitude of the
      velocity drops to values close to zero when the k vector is near to the gap
      minimum. The direction of the velocity also changes around the gap minimum, and
      when the gap is larger in value the change in the velocity direction is more
      gradual. The warping effect does not affect the formation of a Dirac point along
      the k x axis, while it prevents its formation when there is phase shift between
      the two radiations.

PMID- 28437258
TI  - Magnetic resonance study of exchange-biased Ni/NiO nanoparticles.
AB  - Finite sized Ni/NiO nanoparticles (NPs) are prepared by oxidizing pure Ni-NPs in
      an ambient atmosphere with varying annealing time (t A). A synchrotron radiation
      x-ray diffraction technique was used to estimate the grain size, weight fraction
      and lattice parameters of Ni and NiO. The temperature (T) dependencies of
      effective g-factor and line-width of ferromagnetic resonance (FMR) spectra for a
      series of Ni/NiO NPs are determined. Three T-regions with different FMR behaviors
      T  >  200 K, 200  >  T  >  130 K and T  <  130 K are identified. In particular,
      for T  <  200 K, the T-dependency of the g-factor reveals an evolution of
      exchange coupling between Ni and NiO due to the gradual oxidation of Ni NPs.

PMID- 28437259
TI  - Utility of esophageal mucosal impedance as a diagnostic test for esophageal
      disease.
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize the use of direct
      mucosal impedance (MI) for the evaluation and management of esophageal diseases.
      RECENT FINDINGS: Esophageal multichannel intraluminal impedance with pH (MII-pH)
      monitoring has been considered the most sensitive test for gastroesophageal
      reflux disease (GERD), but recent studies have failed to establish impedance
      parameters that reliably predict treatment response to medical and surgical GERD
      therapies. MII-pH uses a catheter passed through the nose, which is uncomfortable
      for patients, and the test is compromised by the day-to-day variability of reflux
      patterns. Recently, an MI device has been developed that can be passed through
      the working channel of an endoscope to measure esophageal epithelial conductivity
      as a marker of chronic GERD. The MI values so obtained are available within
      seconds, correlate with histological findings of epithelial barrier dysfunction,
      normalize with effective treatment, and show promise for diagnosing eosinophilic
      esophagitis and for distinguishing it from GERD. SUMMARY: MI can differentiate
      esophageal disorders instantly during endoscopy, and can monitor treatment
      responses in GERD and eosinophilic esophagitis.

PMID- 28437260
TI  - Early postoperative neuropathic pain assessed by the DN4 score predicts an
      increased risk of persistent postsurgical neuropathic pain.
AB  - BACKGROUND: Acute neuropathic pain can occur in the postoperative period but any
      link with persistent post-surgical neuropathic pain remains unclear. OBJECTIVES:
      The objectives of this study were to prospectively describe the incidence of
      acute post-surgical neuropathic pain in a large population using the DN4
      (clinician administered) questionnaire and to confirm the hypothetical link
      between acute and persistent neuropathic pain at 2 months after surgery in a
      large population using the DN2 (self administered) questionnaire. DESIGN: A multi
      centre, prospective and observational trial. SETTING: Two consecutive days in 27
      hospitals in France. PATIENTS: Six hundred and eight patients undergoing 13
      different types of surgery. Fifteen patients were excluded as data were
      incomplete, and 229 (38.6%) and 260 (43.8%) were not contactable for assessment
      at 1 and 2 months after surgery, respectively. MAIN OUTCOME MEASURES: Pain was
      evaluated at least 2 h postoperatively on the same day (D0),on the second day
      (D2) and at 1 and 2 months after surgery (M1 and M2). Pain was assessed using a
      10-point Numeric Rating Scale. If the Numeric Rating Scale score was greater than
      0, neuropathic pain was assessed using a DN4 (clinician administered)
      questionnaire or using a DN2 (self-administered) questionnaire. Acute and
      persistent postsurgical neuropathic pain (PPSNP) were defined respectively by a
      DN4 score at least 4/10 on day 0 and/or day 2 and a DN2 score at least 3/7 at 2
      months after surgery. RESULTS: Of the 593 patients included, 41.2% were in pain
      before surgery and 8.2% described neuropathic pain. Early after surgery, the
      majority of the 593 patients (72.2% on the day of surgery and 71.3% on day 2)
      experienced acute pain. It was neuropathic in nature in 5.6% of patients (95% CI,
      3.6 to 8.3) on the day of surgery and 12.9% (95% CI, 9.7 to 16.7) on day 2. Two
      months after surgery, PPSNP was present in 33.3% of the 333 patients assessed.
      Multivariate analysis showed that a DN4 score at least 4/10 on the day of surgery
      or on day 2 was a significant risk factor for PPSNP [odds ratios 4.22 (95% CI,
      2.19 to 8.12)]. CONCLUSION: Our results suggest that early acute postsurgical
      neuropathic pain significantly increases the risk of persistent post-surgical
      neuropathic pain. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NTC
      NCT02826317.

PMID- 28437261
TI  - Training in intraoperative handover and display of a checklist improve
      communication during transfer of care: An interventional cohort study of
      anaesthesia residents and nurse anaesthetists.
AB  - BACKGROUND: Handovers during anaesthesia are common, and failures in
      communication may lead to morbidity and mortality. OBJECTIVES: We hypothesised
      that intraoperative handover training and display of a checklist would improve
      communication during anaesthesia care transition in the operating room. DESIGN:
      Interventional cohort study. SETTING: Single-centre tertiary care university
      hospital. PARTICIPANTS: A total of 204 random observations of handovers between
      anaesthesia providers (residents and nurse anaesthetists) over a 6-month period
      in 2016. INTERVENTION: Two geographically different hospital sites were studied
      simultaneously (same observations, but no training/checklist at the control
      site): first a 2-week 'baseline' observation period; then handover training and
      display of checklists in each operating room (at the intervention site only)
      followed by an 'immediate' second and finally a third (3 months later)
      observation period. MAIN OUTCOME MEASURES: A 22-item checklist was created by a
      modified DELPHI method and a checklist score calculated for each handover by
      adding the individual scores for each item as follows: -1, if error in
      communicating item; 0, unreported item; 0.5, if partly communicated item; 1, if
      correctly communicated item. RESULTS: Before training and display of the
      checklist, the scores in the interventional and the control groups were similar.
      There was no improvement in the control group's scores over the three observation
      periods. In the interventional group, the mean (95% confidence interval) score
      increased by 43% [baseline 7.6 (6.7 to 8.4) n = 42; 'immediate' 10.9 (9.4 to
      12.4) n = 27, P < 0.001]. This improvement persisted at 3 months without an
      increase in the mean duration of handovers. CONCLUSION: Intraoperative handover
      training and display of a checklist in the operating room improved the checklist
      score for intraoperative transfer of care in anaesthesia.

PMID- 28437262
TI  - Loss of resistance: A randomised controlled trial assessing four low-fidelity
      epidural puncture simulators.
AB  - BACKGROUND: Detecting loss of resistance (LOR) can either be taught with
      dedicated simulators, with a cost ranging from &OV0556;1500 to 3000, or with the
      'Greengrocer's Model', requiring simply a banana. OBJECTIVES: The purpose of this
      study was to compare three dedicated epidural puncture training simulators and a
      banana in their ability to simulate LOR. Our hypothesis was that there was a
      difference between the four simulators when comparing the detection of LOR.
      DESIGN: Single-blinded, randomised, controlled study. SETTING: Department of
      Anaesthesiology and Pain Therapy, Bern University Hospital, Switzerland.
      PARTICIPANTS: Fifty-five consultant anaesthesiologists. INTERVENTIONS: The
      participants were asked to insert an epidural catheter in four different epidural
      puncture training simulators: Lumbar Puncture Simulator II (Kyoto Kagaku, Kyoto,
      Japan), Lumbar Epidural Injection Trainer (Erler-Zimmer, Lauf, Germany), Normal
      Adult Lumbar Puncture/Epidural Tissue (Simulab Corp., Seattle, Washington, USA)
      and a banana. The simulators were placed in identical boxes to blind the
      participants. MAIN OUTCOME MEASURES: The primary outcome was the detection of LOR
      rated on a 100-mm visual analogue scale, in which 0 mm represented 'completely
      unrealistic' and 100 mm represented 'indistinguishable from a real patient'.
      RESULTS: The mean visual analogue scale scores for LOR in the four simulators
      were significantly different: 60 +/- 25 mm [95% confidence interval (CI), 55 to
      65 mm], 50 +/- 29 mm (95% CI, 44 to 55 mm), 64 +/- 24 mm (95% CI, 58 to 69 mm)
      and 49 +/- 32 mm (95% CI, 44 to 54 mm); P less than 0.001, Friedman test.
      CONCLUSION: Two of the three dedicated epidural simulators were rated more
      realistic in detecting LOR than the banana, but some participants preferred the
      banana to the other three simulators. Given the relative cost of a banana
      compared with a dedicated simulator, we suggest that a banana be used to teach
      the technique of LOR for epidural puncture. TRIAL REGISTRATION: KEK Nr: Req-2015
      z087.

PMID- 28437263
TI  - Evaluation of preoperative oral carbohydrate administration on insulin resistance
      in off-pump coronary artery bypass patients: A randomised trial.
AB  - BACKGROUND: In fasting cardiac surgery patients, preoperative carbohydrate (CHO)
      drink intake attenuated insulin resistance and improved cardiac metabolism,
      although its beneficial effects were not evident after cardiac surgery possibly
      due to cardiopulmonary bypass-related extreme systemic inflammation. OBJECTIVE:
      We aimed to evaluate whether preoperative CHO intake affected insulin resistance
      and free-fatty acid (FFA) concentrations in off-pump coronary revascularisation.
      DESIGN: A randomised controlled trial. SETTING: Primary care in a university
      hospital in Korea from January 2015 to July 2016. PATIENTS: Sixty patients who
      underwent elective multi-vessel off-pump coronary revascularisation were
      randomised into two groups. Three patients were excluded from analysis and 57
      patients completed study. INTERVENTION: The CHO group received oral CHO (400 ml)
      the prior evening and 2 to 3 h before surgery, and the control group was fasted
      from food and water according to standard protocol. MAIN OUTCOME MEASURES:
      Insulin resistance was assessed twice, after anaesthetic induction and after
      surgery via short insulin tolerance test. FFA, C-reactive protein and creatine
      kinase-myocardial band concentrations were determined serially for 48 h after
      surgery. RESULTS: Insulin sensitivity was greater (P = 0.002) and plasma FFA
      concentrations were lower (P = 0.001) after anaesthetic induction in the CHO
      group compared with the Control group, although there were no intergroup
      differences after surgery. The postoperative peak creatine kinase-myocardial band
      concentration was significantly lower in the CHO group compared with the Control
      group [8.8 (5.4 to 18.2) vs. 6.4 (3.5 to 9.7) ng ml, P = 0.031]. CONCLUSION: A
      preoperative CHO supplement significantly reduced insulin resistance and FFA
      concentrations compared with fasting at the beginning of the surgery, but these
      benefits were lost after off-pump coronary revascularisation. Despite their
      transient nature, these beneficial effects resulted in less myocardial injury,
      mandating further studies focused on the impact of preoperative CHO on myocardial
      ischaemia and cardiac function after coronary revascularisation. TRIAL
      REGISTRATION: Clinicaltrials.gov identifier: NCT 02330263.

PMID- 28437264
TI  - Magnesium sulphate improves pulmonary function after video-assisted thoracoscopic
      surgery: A randomised double-blind placebo-controlled study.
AB  - BACKGROUND: Reduced lung volumes are unavoidable after lung resection surgery.
      Magnesium sulphate (MgSO4) administration has been reported to reduce the
      requirement for neuromuscular blocking drugs and postoperative analgesics in
      surgical patients. OBJECTIVE: To investigate the effect of MgSO4 on pulmonary
      function after video-assisted thoracoscopic surgery (VATS). DESIGN: A randomised,
      double-blind, placebo-controlled trial. SETTING: A university tertiary care
      centre. PATIENTS: Sixty-six patients scheduled for pulmonary lobectomy or
      segmentectomy via VATS. INTERVENTION: Patients were allocated to one of two
      groups: the Mg (MgSO4 50 mg kg intravenously for 10 min, followed by a continuous
      infusion of 15 mg kg h during surgery) or the control (same volume of 0.9%
      saline). MAIN OUTCOME MEASURES: Pulmonary function tests [forced expiratory
      volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate]
      were measured before surgery and at three time points after surgery (2, 24 and 48
      h postoperatively) using a portable spirometer. Twelve months after surgery,
      pulmonary function test values were repeated at a regular outpatient follow-up
      visit. RESULTS: FEV1 at 24 (1.7 +/- 0.6 vs. 1.3 +/- 0.5 l, P = 0.033) and 48 h
      (1.7 +/- 0.6 vs. 1.4 +/- 0.5 l, P = 0.021) and FVC at 24 (2.0 +/- 0.8 vs. 1.6 +/-
      0.6 l, P = 0.038) and 48 h (2.2 +/- 0.8 vs. 1.7 +/- 0.7 l, P = 0.008) after
      surgery were significantly greater in the Mg group. Patients in the Mg group
      required less rocuronium than those in the control group (64.2 +/- 19.9 vs. 74.9
      +/- 20.3 mg, respectively; P = 0.041). Consumption of postoperative patient
      controlled analgesia was also significantly less at 24 and 48 h after surgery in
      the Mg group (P = 0.022 and 0.015, respectively), although pain scores and rescue
      analgesics were comparable. Five patients in the control group were diagnosed
      with postoperative pneumonia using clinical and radiological criteria before
      discharge. FEV1 and FVC at 12 months after surgery were not different between the
      two groups. CONCLUSION: Intraoperative administration of MgSO4 improved pulmonary
      function and reduced the need for rocuronium and postoperative analgesics in
      patients who underwent VATS. TRIAL REGISTRATION: cris.nih.go.kr identifier:
      KCT0001410.

PMID- 28437265
TI  - Unilateral Blindness After Septoplasty.
AB  - Septoplasty is a frequently performed procedure with mostly minor complications.
      Nevertheless, it may lead to serious complications.The authors present a 29-year
      old patient admitted to their hospital 10 days after septoplasty in another
      institution. He suffered a total loss of vision immediately after the
      surgery.High-resolution computed tomography and magnetic resonance imaging
      revealed a direct trauma of the optic canal and an inflamed and edematous optic
      nerve. Even though a successful endoscopic optic nerve was performed, the
      patient's loss of vision did not improve after the surgery.Blindness after
      septoplasty is an extremely rare but a devastating complication. There are only
      few patients that indicates the optic nerve injury caused by a direct trauma.

PMID- 28437266
TI  - Gelfoam Interposition Minimizes Risk of Fistula and Postoperative Bleeding in
      Modified-Furlow Palatoplasty.
AB  - Failure to accomplish a tension-free, watertight closure predisposes the
      palatoplasty patient to fistula formation. Perioperative bleeding also places the
      patient at risk for adverse airway events (AAE). This study introduces the
      incorporation of a hemostatic gelatin sponge (Gelfoam) into layered palatoplasty
      to minimize adverse postoperative bleeding and fistula formation. A retrospective
      chart review was performed to identify subjects who underwent Furlow palatoplasty
      with insertion of Gelfoam from 2010 to 2015. Exclusion criteria include age >3
      years, prior palate surgery, <30-day follow-up, immunosuppressive state, and
      diagnosis of Treacher-Collins or Apert Syndrome. Demographic data include age,
      sex, cleft laterality, prior surgeries, Veau classification, Pierre Robin status,
      and tracheostomy dependence. Primary outcome was fistula formation. Secondary
      outcomes included perioperative metrics and AAE.One hundred subjects met
      criteria, 45% female. Average age was 14.6 months. Subjects with syndromes
      comprised 28%, with 16% diagnosed with Pierre Robin. Two subjects were
      tracheostomy-dependent. Prior cleft and mandibular procedures were performed in
      55%. Isolated palatal defects were seen in 46%, unilateral lip and palate in 41%,
      and bilateral lip and palate in 13%. The majority of defects were Veau II and III
      (35% and 34%, respectively). Adverse airway events occurred in 2%, one of which
      resulted in reintubation. One subject (1%) was found to have a postoperative
      fistula.The incorporation of Gelfoam in the modified-Furlow palatoplasty results
      in a low rate of oronasal fistula (1%) and low perioperative risk of AAE. Further
      prospective comparison of this method to others will be the focus of future work.

PMID- 28437267
TI  - Reconstruction of Pediatric Scalp Avulsion Injuries After Dog Bites.
AB  - Dog bite injuries are common and the head and neck is most frequently involved in
      pediatric patients. In severe cases, the combination of crushing, tearing, and
      puncturing can result in scalp avulsion. Currently, microsurgical replantation of
      the avulsed scalp remains the gold standard but may not always be possible. The
      authors present their treatment algorithm with 2 patient examples. In Patient 1,
      the scalp was deemed unsuitable for replantation due to extensive soft tissue
      injury; in Patient 2, the scalp was not available on presentation. Both patients
      underwent debridement and early wound coverage followed by multistage secondary
      revision through serial tissue expansion and excision. At 3-years follow-up, both
      patients have achieved satisfactory aesthetic outcomes following the initial loss
      of 70% and 40% of hair-bearing scalp. There were no infective complications or
      wound dehiscence and the areas of scar alopecia are much improved with
      preservation of the hairline. Pediatric scalp avulsion injuries resulting from
      dog bites are uncommon and involve a unique injury mechanism. Coupled with the
      diminutive size of vessels in this patient population, replantation may be
      precluded altogether. A delayed and staged approach to reconstruction can restore
      a hair-bearing scalp for satisfactory outcomes.

PMID- 28437268
TI  - Anisocoria After Repair of Blowout Fracture.
AB  - Anisocoria may indicate a life-threatening neurosurgical emergency, unlike
      bilateral mydriasis. In patients with periorbital fracture, anisocoria can be
      caused by direct or indirect injury to the oculomotor nerve, excessive retraction
      of the orbital contents, or constriction of the muscles responsible for eyeball
      movement. Herein, the author reports a patient, 15-year-old boy, who developed
      anisocoria after an operation for a blowout fracture. The anisocoria was
      improved, self-limiting, and transient. The author has also reviewed the
      literature regarding anisocoria.

PMID- 28437269
TI  - Outer Side of the Nasal Bone Osteoma.
AB  - Osteomas are located mostly in the mandible followed by paranasal sinuses such as
      frontal sinuses, ethmoid air cells, maxillary sinuses and rarely based on nazal
      cavitiy or turbinate. The osteoma located on outside of nazal bone is extremely
      rare. The authors report an unusual patient of nasal bone osteoma associated with
      aesthetic problem on nasal dorsum. Outer side of nasal bone osteoma in large
      diameter causes aesthetic problems. The authors believe that open rhinoplasty
      approach is successful in this type of patients.

PMID- 28437270
TI  - Surgical Resolution of Bilateral Hypertrophy of Masseter Muscle Through Intraoral
      Approach.
AB  - Masseter muscle hypertrophy is an untypical anomaly with no definite cause and
      its diagnosis is easily completed through physical examination and imaging
      examinations. In some cases, patient may report signs and symptoms of well
      localizated pain. However, it is generally asymptomatic and patient's chief
      complaint is about esthetic because of facial asymmetry. In this case, surgery is
      carefully indicated. The aim of this article is to report a case of a male
      patient with no painful and functional complaints but an important unease over
      his facial asymmetry. Patient underwent surgery involving bilateral resection of
      mandibular angles and unilateral resection of masseter muscle through intraoral
      approach. Surgical approaches and techniques rely heavily on surgeon. There are
      few reports in the literature about this anomaly, but those available present
      several techniques. The surgeon's dexterity and knowledge become extremely
      important, whereas this procedure is essentiallyesthetic.

PMID- 28437271
TI  - Surgical Management of Traumatic Peripheral Osteoma of the Mandible.
AB  - Osteomas are benign osteogenic lesions that result from the proliferation of
      mature bone. Three variants are known: central, peripheral, and extraskeletal.
      The peripheral variant is the most common and it most frequently affects the
      paranasal sinuses, rarely occurring in the jaws. This article describes the case
      of a 33-year-old white male patient who was referred complaining of facial
      asymmetry. Clinical examination revealed an increase in volume at the base of the
      right side of the mandible, hard bony consistency and well delimited, painless to
      the touch, without signs of infection or intraoral alterations. Radiographic
      examination revealed an oval lobulated, radiopaque sessile lesion adhered to the
      mandibular base near the insertion of the masseter muscle. The patient reported
      practicing martial arts many years ago. Owing to the limited access, it was
      decided to perform the complete lesion removal through an extraoral surgical
      approach, by using a skin crease in the upper neck region below the lesion. The
      patient recovered well and the histopathological analysis confirmed the diagnosis
      of osteoma. The etiopathogenesis of osteoma is not completely elucidated, and 3
      theories are more accepted: developmental defect, neoplastic nature, and reactive
      lesion owing to trauma or local infection. The clinicopathological correlation in
      the present case supports a traumatic origin. Traumatic peripheral osteoma should
      be considered in the differential diagnosis of nodular bone-forming lesions
      affecting the mandible.

PMID- 28437274
TI  - Axial Length and Anterior Segment Alterations in Former Preterm Infants and Full
      Term Neonates Analyzed With Scheimpflug Imaging.
AB  - PURPOSE: To compare the axial length and anterior segment alterations in preterm
      infants with and without retinopathy of prematurity with those of full-term
      infants. METHODS: The Wiesbaden Prematurity Study investigated 503 participants
      of former gestational age <=32 weeks and gestational age >=37 weeks now being
      aged 4 to 10 years. This study included 485 participants in the prospective
      controlled cross-sectional, hospital-based study with successful Pentacam
      Scheimpflug imaging. Anterior segment parameters, axial length measurements, and
      associated factors were analyzed. RESULTS: Corneal thickness did not differ
      between former preterm and full-term infants. Significant differences were found
      between preterm and full-term infants now aged <=7 years for spherical
      equivalent, astigmatism, corneal diameter, and axial length. In preterm infants
      aged >=8 years compared with full terms of the same age, we found a significant
      difference only in the corneal diameter. In multivariable analysis of the corneal
      diameter, we detected an association with birth weight and perinatal adverse
      events. Astigmatism correlated with birth weight and laser treatment, anterior
      chamber depth with birth weight, laser treatment and age at examination, and
      axial length with birth weight and age at examination. CONCLUSIONS: This study
      demonstrated altered axial length and anterior segment morphology in former
      preterm infants, especially in the first years of life. In addition, we observed
      that preterm infants seemed to catch up, so that the differences in ocular growth
      in terms of spherical equivalent, astigmatism, and axial length decreased within
      the first 8 years of life.

PMID- 28437273
TI  - Assessing Sensorineural Hearing Loss Using Various Transient-Evoked Otoacoustic
      Emission Stimulus Conditions.
AB  - OBJECTIVES: An important clinical application of transient-evoked otoacoustic
      emissions (TEOAEs) is to evaluate cochlear outer hair cell function for the
      purpose of detecting sensorineural hearing loss (SNHL). Double-evoked TEOAEs were
      measured using a chirp stimulus, in which the stimuli had an extended frequency
      range compared to clinical tests. The present study compared TEOAEs recorded
      using an unweighted stimulus presented at either ambient pressure or
      tympanometric peak pressure (TPP) in the ear canal and TEOAEs recorded using a
      power-weighted stimulus at ambient pressure. The unweighted stimulus had
      approximately constant incident pressure magnitude across frequency, and the
      power-weighted stimulus had approximately constant absorbed sound power across
      frequency. The objective of this study was to compare TEOAEs from 0.79 to 8 kHz
      using these three stimulus conditions in adults to assess test performance in
      classifying ears as having either normal hearing or SNHL. DESIGN: Measurements
      were completed on 87 adult participants. Eligible participants had either normal
      hearing (N = 40; M F = 16 24; mean age = 30 years) or SNHL (N = 47; M F = 20 27;
      mean age = 58 years), and normal middle ear function as defined by standard
      clinical criteria for 226-Hz tympanometry. Clinical audiometry, immittance, and
      an experimental wideband test battery, which included reflectance and TEOAE tests
      presented for 1-min durations, were completed for each ear on all participants.
      All tests were then repeated 1 to 2 months later. TEOAEs were measured by
      presenting the stimulus in the three stimulus conditions. TEOAE data were
      analyzed in each hearing group in terms of the half-octave-averaged signal to
      noise ratio (SNR) and the coherence synchrony measure (CSM) at frequencies
      between 1 and 8 kHz. The test-retest reliability of these measures was
      calculated. The area under the receiver operating characteristic curve (AUC) was
      measured at audiometric frequencies between 1 and 8 kHz to determine TEOAE test
      performance in distinguishing SNHL from normal hearing. RESULTS: Mean TEOAE SNR
      was >=8.7 dB for normal-hearing ears and <=6 dB for SNHL ears for all three
      stimulus conditions across all frequencies. Mean test-retest reliability of TEOAE
      SNR was <=4.3 dB for both hearing groups across all frequencies, although it was
      generally less (<=3.5 dB) for lower frequencies (1 to 4 kHz). AUCs were between
      0.85 and 0.94 for all three TEOAE conditions at all frequencies, except for the
      ambient TEOAE condition at 2 kHz (0.82) and for all TEOAE conditions at 5.7 kHz
      with AUCs between 0.78 and 0.81. Power-weighted TEOAE AUCs were significantly
      higher (p < 0.05) than ambient TEOAE AUCs at 2 and 2.8 kHz, as was the TPP TEOAE
      AUC at 2.8 kHz when using CSM as the classifier variable. CONCLUSIONS: TEOAEs
      evaluated in an ambient condition, at TPP and in a power-weighted stimulus
      condition, had good test performance in identifying ears with SNHL based on SNR
      and CSM in the frequency range from 1 to 8 kHz and showed good test-retest
      reliability. Power-weighted TEOAEs showed the best test performance at 2 and 2.8
      kHz. These findings are encouraging as a potential objective clinical tool to
      identify patients with cochlear hearing loss.

PMID- 28437275
TI  - Descemet Membrane Endothelial Keratoplasty After Failed Descemet Stripping
      Without Endothelial Keratoplasty.
AB  - PURPOSE: To describe the clinical course, surgical experience, and postoperative
      outcomes of 3 patients with Fuchs endothelial dystrophy who underwent Descemet
      membrane endothelial keratoplasty (DMEK) after failed Descemet stripping without
      endothelial keratoplasty. METHODS: Three patients who underwent DMEK for
      management of persistent corneal edema after deliberate Descemet stripping in the
      setting of Fuchs endothelial dystrophy were identified. Patients were examined at
      day 1, week 1, and months 1, 3, and 6 after DMEK. Visual acuity, central corneal
      thickness (CCT), and evaluation of central corneal endothelial cell counts were
      recorded. RESULTS: Two women and one man, aged 56, 72, and 68 years, were
      included. The time interval between primary Descemet stripping and DMEK ranged
      from 3.5 to 8 months. Preoperative visual acuities were 20/200, 20/300, and
      20/80. Immediately before DMEK, no patients had countable central endothelial
      cells, and CCTs were 825, 1034, and 878 MUm. After DMEK, all patients had
      improvement in visual acuity to 20/70, 20/20, and 20/20 with CCTs of 529, 504,
      and 528. The postoperative period in the first case was notable for the immediate
      development of a pigmented pupillary membrane with posterior synechiae, as well
      as cystoid macular edema, of uncertain chronicity, noted 1 month postoperatively.
      The second case also developed posterior synechiae. Two cases completed 6-month
      endothelial cell counts totaling 2200 and 3114 cells per square millimeter
      (endothelial cell loss of 13% and 5.3%). CONCLUSIONS: DMEK is a reliable
      procedure to facilitate corneal rehabilitation and visual recovery in the event
      of poor corneal clearance after Descemet stripping without endothelial
      keratoplasty.

PMID- 28437276
TI  - Clinical Outcome of Rebubbling for Graft Detachment After Descemet Membrane
      Endothelial Keratoplasty.
AB  - PURPOSE: To assess the clinical outcome after successful rebubbling procedures
      for visually significant graft detachment after Descemet membrane endothelial
      keratoplasty (DMEK). METHODS: From a total of 760 consecutive DMEK surgeries, 41
      eyes required rebubbling. Of those, 33 eyes of 31 patients were successful and
      were included in our retrospective outcome analysis study. Main outcome measures
      were compared with those of matched controls with uneventful primary DMEK
      (attached DMEK grafts without rebubbling). Rebubbling was performed on average 25
      (+/-20) days (range 7-91 days) after DMEK. All eyes were evaluated for best
      corrected visual acuity, endothelial cell density (ECD), pachymetry, and
      complications up to 6 months after rebubbling. RESULTS: At 6 months after DMEK,
      best-corrected visual acuity in rebubbled eyes did not differ from that in
      control eyes (P = 0.514). The mean ECD decrease was higher in rebubbled than in
      control eyes (54% vs. 35%, respectively, P = 0.001). Pachymetry did not differ
      between both groups (P = 0.153). After rebubbling, one buphthalmic eye showed
      temporary intraocular pressure elevation and 5 eyes had minor graft edge
      detachment that did not require further treatment. CONCLUSIONS: Rebubbling for
      DMEK graft detachment may result in similar visual outcomes as in uncomplicated
      DMEK, when performed within the first 6 to 8 postoperative weeks. However,
      rebubbled eyes may have lower ECD, which may be attributed to additional air
      bubble trauma and/or selection bias through more extensive manipulation during
      initial DMEK or higher risk of graft detachment in more complicated eyes.

PMID- 28437277
TI  - The Fragile Balance of Community-Based Health Care: One Community's United
      Response When the HIV/AIDS Primary Care Safety Net Failed.

PMID- 28437278
TI  - Pharmacodynamic and -kinetic Behavior of Low-, Intermediate-, and High-Dose
      Landiolol During Long-Term Infusion in Whites.
AB  - Pharmacokinetics, pharmacodynamics, safety, and tolerability of long-term
      administration of landiolol, a fast-acting cardioselective beta-blocker, were
      investigated for the first time in white subjects in a prospective clinical
      trial. Blood concentrations of landiolol and its metabolites, heart rate (HR),
      blood pressure (BP), and electrocardiogram parameters were studied in 12 healthy
      volunteers receiving continuous infusions of a new 12-mg/mL formulation of
      landiolol using a dose-escalation regimen (10 MUg/kg BW/min for 2 hours, 20
      MUg/kg BW/min for 2 hours, 40 MUg/kg BW/min for 20 hours, 6 hours follow-up).
      Landiolol blood concentrations were dose proportional. Time until steady state
      decreased with increasing doses. Pharmacokinetic parameters were t1/2 = 4.5
      minutes, VD = 366 mL/kg, and total body clearance = 53 mL.kg.min. Maximal blood
      concentrations of the inactive main metabolite M1 were 10-fold higher than those
      of landiolol, with t1/2 = 126 minutes, VD = 811 mL/kg, and total body clearance =
      4.5 mL.kg.min. HR reduction from baseline was fast (significant after 16 minutes)
      and sustained throughout the administration period. Systolic and diastolic BP
      reductions and electrocardiogram parameter changes were less pronounced and
      became significant only occasionally. Recovery after discontinuation of infusion
      was fast with little (HR) or no (BP) rebound. The new formulation showed
      excellent local and general tolerability.

PMID- 28437279
TI  - NPY Impairs Cell Viability and Mitochondrial Membrane Potential Through Ca2+ and
      p38 Signaling Pathways in Neonatal Rat Cardiomyocytes.
AB  - NPY is involved in stress cardiomyopathy. However, the associated mechanism for
      NPY-induced stress cardiomyopathy remains unclear. In this study, we aimed to
      explore potential cell signaling pathways that are related to NPY-mediated cell
      viability in neonatal rat cardiomyocytes. We found that NPY induced cell
      viability suppression in cultured cardiomyocytes in a dose-dependent manner.
      After NPY treatment, expression of CaN and p-CAMKII increased significantly, and
      phosphorylation of p38 but not ERK and JNK was changed. Moreover, NPY treatment
      significantly increased PGC-1alpha (the key factor of mitochondrial biogenesis
      and energy metabolism) expression but decreased mitochondrial membrane potential
      in cultured cardiomyocytes. More importantly, the blockage of CaN, CAMKII, and
      p38 signaling pathways by their inhibitors could rescue the reduced cell
      viability and mitochondrial membrane potential in NPY-treated cardiomyocytes.
      Collectively, our data demonstrated that NPY mediated cell viability and
      mitochondrial membrane potential in cardiomyocytes through CaN, CAMKII, and p38
      signaling pathways.

PMID- 28437280
TI  - Inhibition of Rho-kinase Attenuates Left Ventricular Remodeling Caused by Chronic
      Intermittent Hypoxia in Rats via Suppressing Myocardial Inflammation and
      Apoptosis.
AB  - Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea
      syndrome (OSAS), has been reported to play a key role in the development of OSAS
      associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase
      (ROCK) pathway has also been implicated in myocardial remodeling, but the exact
      mechanisms are not fully elucidated. This study's purpose is to investigate the
      influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular
      remodeling in rats and its possible mechanisms. Adult male Sprague-Dawley rats
      suffered from CIH or normoxia stimulus and were intervened with vehicle or
      fasudil (10 mg.kg.d, intraperitoneal injection) for 6 weeks. In this study,
      treatment with fasudil significantly reversed intermittent hypoxia-induced
      histopathological transformations and ultrastructural changes in rat myocardium.
      Moreover, fasudil downregulated the protein levels of RhoA and phosphorylation of
      myosin phosphatase targeting subunit-1 (MYPT1), thus effectively inhibited the
      activation of RhoA/ROCK signaling pathway. Simultaneously, activity of nuclear
      factor (NF)-kB was suppressed by fasudil, which was accompanied by reduced NF-kB
      downstream inflammatory genes including interleukin-6, tumor necrosis factor-a
      and monocyte chemotactic protein-1, and apoptosis. These results suggest that
      fasudil attenuates myocardial remodeling in CIH rats, at least partly by
      suppressing activation of NF-kB. Inhibition of the RhoA/ROCK pathway could become
      an important therapeutic target in the prevention of OSAS-related cardiomyopathy.

PMID- 28437281
TI  - Cardioprotection by Low-dose of Estrogen and Testosterone at the Physiological
      Ratio on Ovariectomized Rats During Ischemia/Reperfusion Injury.
AB  - Although estrogen and testosterone deficiency have often been associated with the
      development of cardiac diseases in postmenopausal women, the benefits of estrogen
      or testosterone therapy are controversial. Supplementation with high dose of
      estrogen or testosterone alone has been associated with many side effects,
      especially estrogen. This study was aimed to investigate whether supplementation
      of testosterone in combination with low-dose estrogen conferred stronger
      cardioprotective effects on ovariectomized rats subjected to ischemia/reperfusion
      injury. Female Sprague Dawley rats were subjected to sham operation (Sham) or
      bilateral ovariectomy (OVX). Two weeks after ovariectomy, OVX rats were treated
      with one of the following: (1) vehicle (OVX), (2) testosterone (100 MUg.kg.d)
      (OVX+T), (3) estrogen (20 MUg.kg.d) (OVX+E), (4) testosterone (100 MUg.kg.d) +
      estrogen (20 MUg.kg.d) (OVX+T+E) for 4 weeks. The hearts were mounted on the
      Langendorff apparatus and subjected to ischemia/reperfusion injury subsequent to
      the determination of hemodynamic parameters. We examined the release of lactate
      dehydrogenase, serum estrogen, and testosterone levels and the expression of
      pAkt/Akt and bax/bcl-2. Testosterone supplementation alone improved the heart
      function, increased p-Akt/Akt and bcl-2 expression, and decreased the release of
      lactate dehydrogenase. Accordingly, these effects of testosterone were more
      pronounced when low-dose estrogen was administered simultaneously, whereas
      estrogen alone at the dose of the experiment had no significant effects. These
      effects might be partially orchestrated by the Akt signaling pathway.

PMID- 28437282
TI  - Inhibition of Mid-chain HETEs Protects Against Angiotensin II-induced Cardiac
      Hypertrophy.
AB  - Recent data demonstrated the role of CYP1B1 in cardiovascular disease. It was,
      therefore, necessary to examine whether the inhibition of CYP1B1 and hence
      inhibiting the formation of its metabolites, using 2,4,3',5'-tetramethoxystilbene
      (TMS), would have a cardioprotective effect against angiotensin II (Ang II)
      induced cardiac hypertrophy. For this purpose, male Sprague Dawley rats were
      treated with Ang II with or without TMS (300 MUg/kg every third day i.p.).
      Thereafter, cardiac hypertrophy and the formation of mid-chain HETEs and
      arachidonic acid were assessed. In vitro, RL-14 cells were treated with Ang II
      (10 MUM) in the presence and absence of TMS (0.5 MUM). Then, reactive oxygen
      species, mitogen-activated protein kinase phosphorylation levels, and nuclear
      factor-kappa B-binding activity were determined. Our results demonstrated that
      TMS protects against Ang II-induced cardiac hypertrophy as indicated by the
      improvement in cardiac functions shown by the echocardiography as well as by
      reversing the increase in heart weight to tibial length ratio caused by Ang II.
      In addition, the cardioprotective effect of TMS was associated with a significant
      decrease in cardiac mid-chain HETEs levels. Mechanistically, TMS inhibited
      reactive oxygen species formation, the phosphorylation of ERK1/2, p38 mitogen
      activated protein kinase, and the binding of p65 NF-kappaB.

PMID- 28437283
TI  - Dilator Use After Vaginal Brachytherapy for Endometrial Cancer: A Randomized
      Feasibility and Adherence Study.
AB  - BACKGROUND: Vaginal brachytherapy, a common treatment of endometrial cancer, is
      associated with high rates of vaginal stenosis. Recommendations for vaginal
      dilator use to minimize stenosis generally include 3 times per week for
      approximately 10 minutes per use. However, adherence rates range widely and are
      generally well less than 50%. OBJECTIVES: The aims of this study were to assess
      feasibility of recruitment to a study of dilator use and test a theoretically
      driven enhanced educational program (EEP) to increase adherence. METHODS:
      Eligibility included women treated with postoperative vaginal brachytherapy for
      stage I to IIIc endometrial cancer. Patients were randomized to either nurse
      delivered standard institutional instruction or EEP. RESULTS: Of eligible
      patients, 76% consented, 42 were randomized, and 69% completed the 6-month
      assessment. Mean age was 58.2 years; 48% were sexually active. There was no
      difference in adherence between arms. Overall, 20% and 8.3% were adherent to the
      prescribed use of 3 times per week, and 64% and 16% were adherent to use at least
      once per week at 6 weeks and 6 months, respectively. Adherence was greater among
      those motivated by vaginal health and having lower body mass index. Nonadherence
      was significantly higher among those who are college educated, in the EEP group,
      and with higher weight. CONCLUSIONS: Feasibility of recruitment into a study of
      vaginal dilator use was high. Adherence was low, and there was no difference
      between groups. Adherence to vaginal dilator use requires novel interventions to
      test. IMPLICATIONS FOR PRACTICE: Nursing education that includes how dilators may
      maintain vaginal health may improve use because it was a motivator for adherence
      in this study.

PMID- 28437284
TI  - A Retrospective Study on Mycophenolic Acid Drug Interactions: Effect of
      Prednisone, Sirolimus, and Tacrolimus With MPA.
AB  - Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is
      widely used as an antirejection drug after renal transplantation. There is
      growing evidence supporting the notion that there is substantial variability in
      the intra- and interpatient exposure to MPA. Drug interactions involving MPA with
      tacrolimus, steroids, and sirolimus have been understudied. The objective of this
      study was to determine the relationship between MPA, steroids, tacrolimus, and
      sirolimus. MPA trough concentrations from 37 pediatric renal transplant
      recipients (mean age 7.6 years at transplant) followed for a median follow-up of
      7.8 years were analyzed retrospectively and 2131 dose-normalized MPA trough
      concentrations were evaluated against all known covariates including all
      concomitant immunosuppressant drug doses and exposure, age, albumin, hematocrit,
      and estimated glomerular filtration rate (eGFR). Age, hematocrit, and estimated
      glomerular filtration rate affected the dose-normalized MPA trough
      concentrations. The authors used appropriate linear regression univariate models
      and created 5 different multivariate models to examine individual drug-drug
      interactions (DDIs). Although the authors' findings support the notion that there
      is a DDI between MMF and both sirolimus and steroids, the sample size was small,
      and these findings should be confirmed in future studies. The authors found no
      DDIs between tacrolimus and MMF, the prodrug of MPA. These findings are important
      because there is a tendency to under-dose MMF early and to overdose late after
      transplantation. The DDI between sirolimus and MMF has not been described.
      Although therapeutic drug monitoring of MMF therapy is often not performed, the
      data presented here indicate a necessity for therapeutic drug monitoring. This is
      especially true when converting from tacrolimus to sirolimus, as a way to avoid
      MPA underexposure and organ rejection.

PMID- 28437285
TI  - Monitoring Protein-Unbound Valproic Acid Serum Concentrations in Clinical
      Practice.
AB  - BACKGROUND: Valproic acid (VPA) is an effective antiepileptic drug and mood
      stabilizer. A key characteristic of VPA is its high and saturable protein binding
      at higher concentrations. Although the unbound concentration of VPA is
      responsible for its pharmacological activity, total drug concentrations are
      monitored in routine clinical practice. Therapeutic drug monitoring (TDM) of
      unbound VPA is recommended for specific clinical situations. The goal of this
      study was to evaluate TDM requests for unbound VPA in clinical practice. METHODS:
      All TDM requests at our laboratory for unbound VPA in 2014 and 2015 were
      evaluated retrospectively. In patients with potentially toxic unbound VPA
      concentrations (ie, >12 mg/L), we evaluated whether toxicity was noted and
      whether the dose adjustment advice was followed. Total and unbound VPA
      concentrations were measured by means of a validated immunoassay. RESULTS: A
      total of 273 unbound VPA serum concentrations in 132 different patients were
      analyzed. The main reasons for unbound VPA TDM were decreased renal function
      (34%) and a low serum albumin (27%). The median (range) unbound VPA concentration
      was 9.8 (2.5-47.6) mg/L. In 49 patients (37%), the initial unbound VPA
      concentration was above the threshold of 12 mg/L, potentially resulting in
      toxicity. Only 6 of these 49 patients had elevated total VPA concentrations.
      Clinical toxicity was noted in 38 of the 49 patients (77.6%) with elevated
      unbound VPA concentrations. Toxicities included drowsiness (n = 26), decreased
      consciousness (n = 4), rigidity (n = 2), and confusion (n = 2). In 36 of the 38
      patients with elevated unbound VPA concentrations and clinical toxicity, a dose
      reduction was applied. In 27 of 36 patients who had their dose reduced, dose
      reduction was associated with improvement or resolution of VPA toxicity.
      CONCLUSIONS: TDM of unbound VPA is an important tool to manage VPA therapy in
      selected, vulnerable patients.

PMID- 28437286
TI  - Cut the "Gordian Knot".

PMID- 28437287
TI  - Allocation of Organs Should be Based on the Current Status of Medical Science.

PMID- 28437289
TI  - Congenital Pseudarthrosis of the Tibia.

PMID- 28437290
TI  - Remission Following Paclitaxel and Cisplatin Treatment in a 15-Year-Old Patient
      With Unresectable Esophageal Squamous Cell Cancer.

PMID- 28437291
TI  - Behcet Disease Initially Presenting as Deep Venous Thrombosis: A Case Report.
AB  - Behcet disease is a potentially life-threatening multisystemic vasculitis with
      thrombotic tendency. Mucocutaneous ulcers, arthritis, and uveitis are the most
      recognizable features, but may be absent at the time of medical evaluation. We
      report a case in which a 8-year old patient presented with spontaneous bilateral
      lower extremity deep venous thromboses, and screening for rheumatologic symptoms
      led to diagnosing Behcet. This case demonstrates that deep venous thromboses can
      be the initial event bringing a patient with Behcet to medical attention,
      highlighting the importance of screening for underlying rheumatologic diseases in
      pediatric patients who present with unprovoked thrombosis.

PMID- 28437292
TI  - Use of Electronic Consultation System to Improve Access to Care in Pediatric
      Hematology/Oncology.
AB  - BACKGROUND: Electronic consultations (eConsult) allow for communication between
      primary care providers and specialists in an asynchronous manner. This study
      examined provider satisfaction, topics of interest, and efficiency of eConsult in
      pediatric hematology/oncology in Ottawa, Canada. METHODS: We conducted a cross
      sectional assessment of all eConsult cases directed to pediatric
      hematology/oncology specialists using the Champlain BASE (Building Access to
      Specialists through eConsultation) eConsult service from June 1, 2014 to May 31,
      2016. RESULTS: There were 1064 eConsults to pediatrics during the study
      timeperiod and pediatric hematology/oncology consults accounted for 8% (85).
      During the same study timeperiod, 524 consults were seen in the pediatric
      hematology/oncology clinic. The majority of the eConsults were for hematology
      (90.5%) in contrast to oncology topics (9.5%). The most common topics were
      anemia, hemoglobinopathy, bleeding disorder, and thrombotic state. Primary care
      providers rated the eConsult service very highly, and their comments were very
      positive. The eConsult service resulted in deferral of 40% of consults originally
      contemplated to require a face-to-face specialist visit. CONCLUSIONS: This study
      showed successful implementation and use of the eConsult service for pediatric
      hematology/oncology and resulted in avoidance of a large number of face-to-face
      consultation. The common topics identified areas for continuing medical
      education.

PMID- 28437293
TI  - Increased Cancer Incidence in the Local Population Around Metal-Contaminated
      Glassworks Sites.
AB  - OBJECTIVE: The aim of this study was to examine mortality causes and cancer
      incidence in a population cohort that have resided in close proximity to highly
      metal-contaminated sources, characterized by contamination of, in particular,
      arsenic (As), cadmium (Cd), and lead (Pb). METHODS: Data from Swedish registers
      were used to calculate standardized mortality and cancer incidence ratios. An
      attempt to relate cancer incidence to metal contamination levels was made.
      RESULTS: Significantly elevated cancer incidences were observed for overall
      malignant cancers in both genders, cancer in the digestive system, including
      colon, rectum, and pancreas, and cancers in prostate among men. Dose-response
      relationships between Cd and Pb levels in soil and cancer risks were found.
      CONCLUSIONS: Cancer observations made, together with previous studies of metal
      uptake in local vegetables, may imply that exposure to local residents have
      occurred primarily via oral intake of locally produced foodstuffs.

PMID- 28437294
TI  - Sleep Detriments Associated With Quick Returns in Rotating Shift Work: A Diary
      Study.
AB  - OBJECTIVE: We aimed to compared sleep characteristics associated with quick
      returns (QRs, <11 hours between shift intervals) with those associated with other
      common shift transitions. METHODS: Sixty-seven nurses completed a 2-week work and
      sleep diary (94.0% female, mean age 47.7 years). A multilevel fixed effects model
      was used to examine the sleep in QRs compared with two consecutive night shifts,
      two consecutive evening shifts, and two consecutive day shifts, respectively.
      RESULTS: None of the other shift transitions studied encumbered as many
      detriments as QRs, which included short sleep duration (5.6 hours), slightly
      prolonged sleep onset latency, more abrupt ending of main sleep period, increased
      sleepiness, and higher level of perceived stress on the following shift.
      CONCLUSION: The study emphasizes the need for sufficient time for rest and
      recuperation between shifts.

PMID- 28437295
TI  - Clozapine-Associated Agranulocytosis Treatment With Granulocyte Colony
      Stimulating Factor/Granulocyte-Macrophage Colony-Stimulating Factor: A Systematic
      Review.
AB  - PURPOSE/BACKGROUND: Clozapine is associated with hematological abnormalities,
      notably neutropenia, which may progress to agranulocytosis. Granulocyte colony
      stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor
      (GM-CSF) have been used to reduce the frequency and duration of clozapine
      associated neutropenia. This review aims to explore the use, efficacy, and
      tolerability of these cytokines in the treatment of clozapine-associated
      agranulocytosis. METHODS/PROCEDURES: We conducted a systematic review of
      published interventional and observational studies, case series, and case reports
      where G-CSF/GM-CSF was used to treat clozapine-associated agranulocytosis.
      FINDINGS/RESULTS: We identified 29 reports (40 patients). The median duration of
      neutrophil recovery time after stopping clozapine and starting cytokine treatment
      was 7 days (range, 2-13 days) for those with agranulocytosis (absolute neutrophil
      count < 0.5 * 10 cells/L). Ninety-four percent (n = 29) had no serious adverse
      reactions, and no deaths occurred. IMPLICATIONS/CONCLUSIONS: Our findings
      indicate that G-CSF/GM-CSF use is well tolerated and suggest that G-CSF can
      sometimes be safely used to reduce the duration of neutropenia associated with
      clozapine use. However, the interpretation of this outcome is difficult, given
      the likely publication bias for positive outcomes in case reports.

PMID- 28437296
TI  - From the Editors.

PMID- 28437297
TI  - PEARL-Pain in Early Life: A New Network for Research and Education.

PMID- 28437298
TI  - An Innovation in the Assessment of Labor Pain.

PMID- 28437300
TI  - Education, Competency, Certification, Credentialing: What's the Difference?

PMID- 28437299
TI  - Analgesia in the Premature Neonate: Walking the Tightrope Requires a Great Team.

PMID- 28437301
TI  - Dexmedetomidine: A Solution to the Dilemma of Pain and Agitation in the
      Mechanically Ventilated Preterm Neonate?

PMID- 28437302
TI  - Pain Management in the Opioid-Dependent Pregnant Woman.
AB  - Opioid dependence is an epidemic in the United States, and the percentage of
      pregnant women who are opioid dependent has increased dramatically in the last
      decade. Pain management, already a concern for intrapartum and postpartum care,
      is complicated in the context of opioid dependence. This clinical review surveys
      the literature on pain management in opioid-dependent pregnant women to summarize
      current consensus and evidence to guide clinical practice. Points of consensus
      for pain management in opioid-dependent pregnant women include continual opioid
      maintenance therapy throughout the pregnancy and the postpartum period; adequate
      management of acute pain; the contraindication of opioid agonist-antagonists for
      pain management; and the need for interdisciplinary teams using a multimodal
      approach to provide optimal care to opioid-dependent pregnant women.

PMID- 28437303
TI  - Pain Management in the Opioid-Dependent Pregnant Woman.

PMID- 28437304
TI  - Nitrous Oxide Utility in Labor and Birth: A Multipurpose Modality.
AB  - The use of nitrous oxide (N2O) for labor and birth has very recently emerged as a
      viable modality in the United States, despite a long history of use in Canada and
      Europe. Usually associated with dental procedures, there are significant
      differences between dental and parturition utility, efficacy, and staff exposure.
      In addition to using it for pain relief and anxiolysis, those centers utilizing
      it have noted it to be multipurpose and useful for such situations as: external
      cephalic version, manual removal of placenta, intravenous starts, during
      placement of urinary catheters and intracervical Foley bulbs. Nitrous oxide has
      proven to be especially helpful for repair of lacerations under local anesthesia
      and is a multiuse modality that should be available to women in all birth
      settings. This article explores the history of N2O use, provides a comparison of
      obstetrical use to use in the dental industry, examines the contraindications to,
      and implications for usage, and discusses logistical points of consideration for
      clinicians working with women using N2O for labor and birth.

PMID- 28437306
TI  - Breast-Feeding Analgesia in Infants: An Update on the Current State of Evidence.

PMID- 28437305
TI  - Breast-Feeding Analgesia in Infants: An Update on the Current State of Evidence.
AB  - To provide an updated synthesis of the current state of the evidence for the
      effectiveness of breast-feeding and expressed breast milk feeding in reducing
      procedural pain in preterm and full-term born infants. A systematic search of key
      electronic databases (PubMed, CINAHL, EMBASE) was completed. Of the 1032
      abstracts screened, 21 were found eligible for inclusion. Fifteen studies
      reported on the use of breast-feeding or expressed breast milk in full-term
      infants and 6 reported on preterm infants. Direct breast-feeding was more
      effective than maternal holding, maternal skin-to-skin contact, topical
      anesthetics, and music therapy, and was as or more effective than sweet tasting
      solutions in full-term infants. Expressed breast milk was not consistently found
      to reduce pain response in full-term or preterm infants. Studies generally had
      moderate to high risk of bias. There is sufficient evidence to recommend direct
      breast-feeding for procedural pain management in full-term infants. Based on
      current evidence, expressed breast milk alone should not be considered an
      adequate intervention.

PMID- 28437307
TI  - Blood Sampling in Newborns: A Systematic Review of YouTube Videos.
AB  - Objective of this study was to conduct a systematic review of YouTube videos
      showing neonatal blood sampling, and to evaluate pain management and comforting
      interventions used. Selected videos were consumer- or professional-produced
      videos showing human newborns undergoing heel lancing or venipuncture for blood
      sampling, videos showing the entire blood sampling procedure (from the first
      attempt or puncture to the time of application of a cotton ball or bandage),
      publication date prior to October 2014, Portuguese titles, available audio.
      Search terms included "neonate," "newborn," "neonatal screening," and "blood
      collection." Two reviewers independently screened the videos and extracted the
      following data. A total of 13 140 videos were retrieved, of which 1354 were
      further evaluated, and 68 were included. Videos were mostly consumer produced
      (97%). Heel lancing was performed in 62 (91%). Forty-nine infants (72%) were held
      by an adult during the procedure. Median pain score immediately after puncture
      was 4 (interquartile range [IQR] = 0-5), and median length of cry throughout the
      procedure was 61 seconds (IQR = 88). Breastfeeding (3%) and swaddling (1.5%) were
      rarely implemented. Posted YouTube videos in Portuguese of newborns undergoing
      blood collection demonstrate minimal use of pain treatment, and maximal distress
      during procedures. Knowledge translation strategies are needed to implement
      effective measures for neonatal pain relief and comfort.

PMID- 28437308
TI  - Effectiveness of ShotBlocker for Immunization Pain in Full-Term Neonates: A
      Randomized Controlled Trial.
AB  - Nonpharmacologic strategies exist to manage procedural pain in healthy newborn
      infants. The aim of this prospective randomized controlled trial (RCT) was to
      examine the efficacy of ShotBlocker for managing injection pain associated with
      the first intramuscular hepatitis B vaccine given to healthy full-term neonates.
      This randomized controlled trial study was conducted in a private university
      hospital in Istanbul, Turkey, in which 100 healthy term neonates were randomly
      assigned to either a ShotBlocker (n = 50) or control group (n = 50). The Neonatal
      Infant Pain Scale scores of the neonates in the ShotBlocker and control groups
      were compared before, during, and after the injections, and the physiological
      parameters were compared before and after the procedure. The pain scores of the
      neonates during (ShotBlocker group: 1.64 +/- 0.80; control group: 2.96 +/- 0.73)
      and after (ShotBlocker group: 0.74 +/- 0.66; control group: 1.42 +/- 0.76) the
      injection procedure were lower in the ShotBlocker group than in the control group
      (P = .000). The postinjection heart rate in the infants in the ShotBlocker group
      (145.02 +/- 13.50) was found to be lower than in those for whom ShotBlocker was
      not used (150.24 +/- 13.36) (P = .05). The use of ShotBlocker during the
      hepatitis B vaccine in term neonates is effective in reducing the acute pain.

PMID- 28437309
TI  - Pain Management During Newborn Screening: Using YouTube to Disseminate Effective
      Pain Management Strategies.
AB  - To assess the reach, acceptability, and effect of the BSweet2Babies video showing
      breast-feeding, skin-to-skin care, and sucrose during blood sampling on intention
      to recommend the video or advocate for use of the interventions. In July 2014,
      the video and an electronic survey were produced and posted. After 1 year, the
      online viewer survey responses and YouTube analytics were analyzed. One year
      after posting, the BSweet2Babies video had 10 879 views from 125 countries and
      187 (1.7%) viewers completed the survey. Most respondents were aware of the
      analgesic effects of breast-feeding, skin-to-skin care, and sucrose. Nearly all
      respondents (n = 158, 92%) found the BSweet2Babies video to be a helpful resource
      and 146 (84%) answered that they would recommend the video to others. After
      viewing the video, 183 (98%) respondents answered that they would advocate for 1
      or more of the interventions. The BSweet2Babies video showing effective pain
      treatment during blood sampling had a large reach but a very small response rate
      for the survey. Therefore, analysis of acceptability and effect on intention to
      recommend the video and advocate for the interventions depicted are limited.
      Further research is warranted to explore how to best evaluate videos delivered
      through social media and to determine the effect of the video to promote
      knowledge translation into clinical practice.

PMID- 28437310
TI  - Neurobiological Consequences of Early Painful Experience: Basic Science Findings
      and Implications for Evidence-Based Practice.
AB  - As healthcare teams have worked to improve infant survival rates, the management
      of painful events experienced by these hospitalized neonates has increased and
      yet pain management remains highly variable between healthcare institutions. At
      the same time, emerging evidence suggests that these early painful experiences
      may alter the trajectory of development for pain-processing pathways both
      peripherally and centrally. This concise review highlights findings from both the
      basic and clinical science literature supporting the hypothesis that early
      painful experiences can have long-lasting negative effects on biological,
      psychological, and socioemotional functions. Implications for pain management in
      neonates and considerations for evidence-based practice change are discussed.

PMID- 28437311
TI  - The Impact of a Hospital Garden on Pregnant Women and Their Partners.

PMID- 28437312
TI  - Assessment of Sarcopenia as a Predictor of Poor Outcomes After Esophagectomy in
      Elderly Patients With Esophageal Cancer.
AB  - OBJECTIVE: The objective of the study was to elucidate the impact of sarcopenia
      in elderly patients with esophageal cancer on postoperative complications and
      long-term survival after surgery for esophageal cancer. SUMMARY BACKGROUND DATA:
      Sarcopenia, defined as loss of skeletal muscle mass with age, has been identified
      as a poor prognostic factor for malignancies. This retrospective study
      investigated the effect of sarcopenia on surgical outcomes among young and
      elderly patients with esophageal cancer. METHODS: Data were collected for 341
      consecutive patients who underwent esophagectomy for esophageal cancer. Patients
      were assigned to 2 groups according to age (younger than 65 years and 65 years or
      older) and the presence of sarcopenia. RESULTS: Sarcopenia was present in 170 of
      341 patients (49.9%) with esophageal cancer and in 74 of 166 elderly patients
      (44.6%). The incidence of anastomotic leak and in-hospital death was
      significantly higher in the elderly sarcopenia group than in the elderly
      nonsarcopenia group (31.5% vs 15.2%, P = 0.015, 6.8 vs 0.0%, P = 0.037,
      respectively), and the overall survival rate in patients with sarcopenia
      correlated with a significantly poor prognosis in the elderly group (P < 0.001).
      Multivariate analysis revealed that sarcopenia was a risk factor for an
      anastomotic leak (P = 0.034) and was an unfavorable prognostic factor for
      survival (P < 0.001). Those correlations between sarcopenia and surgical outcomes
      were not observed in the young group. CONCLUSIONS: Sarcopenia and worse surgical
      outcomes were significantly associated patients with in esophageal cancer aged 65
      years and older but not in those younger than 65 years.

PMID- 28437313
TI  - Enhanced Recovery After Surgery for Noncolorectal Surgery?: A Systematic Review
      and Meta-analysis of Major Abdominal Surgery.
AB  - OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS)
      protocols across noncolorectal abdominal surgical procedures. BACKGROUND: ERAS
      programs have been studied extensively in colorectal surgery and adopted at many
      centers. Several studies testing such protocols have shown promising results in
      improving postoperative outcomes across various surgical procedures. However,
      surgeons performing major abdominal procedures have been slower to adopt these
      ERAS protocols. METHODS: A systematic review was performed using "enhanced
      recovery after surgery" or "fast track" as search terms and excluded studies of
      colorectal procedures. Primary endpoints for the meta-analysis include length of
      stay (LOS) and complication rate. Secondary endpoints were time to first flatus,
      readmission rate, and costs. RESULTS: A total of 39 studies (6511 patients) met
      inclusion and exclusion criteria. Among them 14 studies were randomized trials,
      and the remaining 25 studies were cohort studies. Meta-analysis showed a decrease
      in LOS of 2.5 days (95% confidence interval, CI: 1.8-3.2, P < 0.001) and a
      complication rate of 0.70 (95% CI: 0.56-0.86, P = 0.001) for patient treated in
      ERAS programs. There was also a significant reduction in time to first flatus of
      0.8 days (95% CI: 0.4-1.1, P < 0.001) and cost reduction of $5109.10 (95% CI:
      $4365.80-$5852.40, P < 0.001). There was no significant increase in readmission
      rate (OR 1.03, 95% CI: 0.84-1.26, P = 0.80) in our analysis. CONCLUSIONS: ERAS
      protocols decreased length of stay and cost by not increasing complications or
      readmission rates. This study adds to the evidence that ERAS protocols are safe
      to implement and are beneficial to surgical patients and the healthcare system
      across multiple abdominal procedures.

PMID- 28437314
TI  - Outcome for Patients With Pathological Esophageal Acid Exposure After
      Laparoscopic Fundoplication.
AB  - OBJECTIVE: The aim of the current study was to assess symptomatic outcome and
      need for surgical reintervention for patients identified with pathological
      esophageal acid exposure by routine postoperative 24-hour pH-monitoring.
      BACKGROUND: Although laparoscopic fundoplication is associated with excellent
      short- and midterm results, recurrent symptoms pose an important challenge.
      Postoperative pH-monitoring is considered the "gold standard" for diagnosing
      recurrent GERD and frequently used for routine postoperative follow up. METHODS:
      Analysis of prospectively collected data from patients who underwent laparoscopic
      fundoplication between April 1994 and June 2015 and underwent routine
      postoperative 24-hour pH-monitoring was performed. Symptomatic outcome and need
      for surgical reintervention up to 5 years was compared between patients with
      pathological and physiological postoperative esophageal acid exposure. Primary
      endpoints were heartburn score and need for surgical reintervention for recurrent
      reflux. RESULTS: A total of 309 patients in whom routine postoperative 24-hour pH
      monitoring was performed were included. Pathological acid exposure was present in
      33 patients (11%) compared with 276 patients (89%) with physiological acid
      exposure. During 5-year follow up, there were no differences in heartburn,
      dysphagia, or satisfaction scores. Eighteen percent of all patients with abnormal
      postoperative pH-studies underwent redo fundoplication during 5-year follow up.
      CONCLUSIONS: Pathological acid exposure demonstrated by routine postoperative pH
      monitoring was not associated with worse symptomatic outcome in terms of reflux
      control and satisfaction. A possible explanation for this finding is that
      laparoscopic fundoplication reduces the patients' ability to perceive reflux.
      This underlines the importance of assessing the association between symptomatic
      outcome and esophageal function tests in determining outcome of antireflux
      surgery.

PMID- 28437315
TI  - Lateral Node Dissection in Low Rectal Cancer: Time for a Global Approach?

PMID- 28437316
TI  - Attitudes of Physician Assistant Educators Toward Interprofessional Education and
      Collaborative Care.
AB  - PURPOSE: Interprofessional education (IPE) has been shown to improve
      collaboration in the workforce, ultimately improving patient care. The purpose of
      this study was to evaluate physician assistant (PA) educators' attitudes toward
      IPE and interprofessional (IP) health care teams. METHODS: An online survey was
      sent to 1198 PA educators. The survey assessed 3 domains: attitudes toward IPE,
      attitudes toward IP health care teams, and attitudes toward IP learning in the
      academic setting. RESULTS: Most participants were involved in some form of IPE.
      Faculty attitudes were positive in all 3 domains but were more favorable toward
      IPE. CONCLUSIONS: The positive attitudes held by PA faculty members may change
      the way in which curricula are conceived and delivered, influencing IP
      collaboration of future health care providers.

PMID- 28437317
TI  - Dementia, Comorbidity, and Physical Function in the Program of All-Inclusive Care
      for the Elderly.
AB  - BACKGROUND: Participants in the Program of All-Inclusive Care for the Elderly
      (PACE) are a unique clinical population of medically complex and highly disabled
      older adults who qualify for nursing home level care but receive services in the
      community. A main goal of PACE programs is to prevent further declines in
      physical function that may necessitate costly institutionalization. This study
      evaluates how multimorbidity and dementia impact both self-selected gait speed
      and Timed Up and Go (TUG) in this population. METHODS: This study was a cross
      sectional design. Sociodemographic information, physical function, comorbidity
      data, and dementia status on 525 PACE participants were extracted from a quality
      improvement database. Separate univariable and multivariable linear regression
      models were used to evaluate the impact of comorbidity status and dementia on
      gait speed and TUG time. RESULTS: PACE participants overall have a high degree of
      functional disability, with an average gait speed of 0.66 m/s, an average Short
      Physical Performance Battery score of 6.0/12, and an average TUG time nearly 20
      s. In the univariable analysis, a higher number of comorbidities and a diagnosis
      of dementia were associated with greater limitation for gait speed and TUG time.
      After adjusting for age, sex, strength, and balance, each additional comorbidity
      was independently associated with 0.015 m/s slower gait speed, as well as a 3.5%
      increase in TUG time for PACE participants with dementia. CONCLUSIONS: Ambulatory
      PACE participants have average levels of physical function that are dangerously
      close to thresholds thought to indicate vulnerability for further disability
      development, hospitalization, and nursing home admission. Both dementia and
      comorbidity burden are associated with declines in physical function, and the
      interaction between these risk factors is a telling indicator to functional
      decline in higher-level ambulatory tasks. PACE program clinicians can use this
      information to better identify participants at risk for limited physical
      function. Further research should investigate consequences of functional decline
      and determine optimal intervention strategies for PACE participants with
      functional impairments.

PMID- 28437318
TI  - RESULTS OF MACULAR HOLE SURGERY: Evaluation Based on the International
      Vitreomacular Traction Study Classification.
AB  - PURPOSE: To evaluate the differences in anatomical and visual function changes
      after macular hole (MH) surgery using the International Vitreomacular Traction
      Study classification. METHODS: Patients who underwent vitrectomy and blood
      assisted internal limiting membrane peeling because of MHs were enrolled in the
      present study. The patients were divided into three groups according to the sizes
      of their MHs (small: <=250 MUm, medium: >250 MUm and <=400 MUm, and large: >400
      MUm). The effect of vitreomacular traction on the outcome was also analyzed. All
      the patients were followed for at least 12 months. The changes in best-corrected
      visual acuity and the outer retina at the foveal area were monitored using
      spectral-domain optical coherence tomography. RESULTS: A total of 146 eyes of 146
      patients were enrolled. The patients with small MHs showed significantly better
      mean final visual acuity (mean: 20/58) than patients with large MHs (20/178, P <
      0.05). There was no significant difference between patients with small- and
      medium-sized MHs (20/69). Longitudinal analysis showed that the presence of
      vitreomacular traction was related to a better restoration of the outer retinal
      structure and visual acuity. CONCLUSION: Patients with smaller MHs and
      vitreomacular adhesion had superior final visual acuity and better restoration of
      the outer retinal structure after MH surgery.

PMID- 28437319
TI  - Quality of Antiepileptic Treatment Among Older Medicare Beneficiaries With
      Epilepsy: A Retrospective Claims Data Analysis.
AB  - BACKGROUND: Enzyme-inducing antiepileptic drugs (EI-AEDs) are not recommended for
      older adults with epilepsy. Quality Indicator for Epilepsy Treatment 9 (QUIET-9)
      states that new patients should not receive EI-AEDs as first line of treatment.
      In light of reported racial/ethnic disparities in epilepsy care, we investigated
      EI-AED use and QUIET-9 concordance across major racial/ethnic groups of Medicare
      beneficiaries. RESEARCH DESIGN: Retrospective analyses of 2008-2010 Medicare
      claims for a 5% random sample of beneficiaries 67 years old and above in 2009
      augmented for minority representation. Logistic regressions examined QUIET-9
      concordance differences by race/ethnicity adjusting for individual,
      socioeconomic, and geography factors. SUBJECTS: Epilepsy prevalent (>=1
      International Classification of Disease-version 9 code 345.x or >=2 International
      Classification of Disease-version 9 code 780.3x, >=1 AED), and new (same as
      prevalent+no seizure/epilepsy events nor AEDs in 365 d before index event) cases.
      MEASURES: Use of EI-AEDs and QUIET-9 concordance (no EI-AEDs for the first 2
      AEDs). RESULTS: Cases were 21% white, 58% African American, 12% Hispanic, 6%
      Asian, 2% American Indian/Alaskan Native. About 65% of prevalent, 43.6% of new
      cases, used EI-AEDs. QUIET-9 concordance was found for 71% Asian, 65% white, 61%
      Hispanic, 57% African American, 55% American Indian/Alaskan new cases:
      racial/ethnic differences were not significant in adjusted model. Beneficiaries
      without neurology care, in deductible drug benefit phase, or in high poverty
      areas were less likely to have QUIET-9 concordant care. CONCLUSIONS: EI-AED use
      is high, and concordance with recommendations low, among all racial/ethnic groups
      of older adults with epilepsy. Potential socioeconomic disparities and drug
      coverage plans may affect treatment quality and opportunities to live well with
      epilepsy.

PMID- 28437320
TI  - Development of a Claims-based Frailty Indicator Anchored to a Well-established
      Frailty Phenotype.
AB  - BACKGROUND: Fried and colleagues described a frailty phenotype measured in the
      Cardiovascular Health Study (CHS). This phenotype is manifest when >=3 of the
      following are present: low grip strength, low energy, slowed waking speed, low
      physical activity, or unintentional weight loss. We sought to approximate frailty
      phenotype using only administrative claims data to enable frailty to be assessed
      without physical performance measures. STUDY DESIGN: We used the CHS cohort data
      linked to participants Medicare claims. The reference standard was the frailty
      phenotype measured at visits 5 and 9. With penalized logistic regression, we
      developed a parsimonious index for predicting the frailty phenotype using a
      linear combination of diagnoses, operationalized with claims data. We assessed
      the predictive validity of frailty index by examining how well it predicted
      common aging-related outcomes including hospitalization, disability, and death.
      RESULTS: There were 4454 CHS participants from 4 clinical sites. In total, 84%
      were white, 58% were women and their mean age was 72 years at enrollment.
      Approximately 11% of the cohort was frail. The model had an area under the
      receiver operating curve of 0.75 to concurrently predict a frailty phenotype.
      This Claims-based Frailty Indicator significantly predicted death (odds ratio,
      1.84), time to death (hazards ratio, 1.71), number of hospital admissions
      (incidence rate ratio, 1.74), and nursing home admission (odds ratio, 1.47) in
      models adjusted for age and sex. CONCLUSIONS: Claims data alone can be used to
      classify individuals as frail and nonfrail. The Claims-based Frailty Indicator
      might be used in research with large datasets for confounding adjustment or risk
      prediction. The indicator might also be used for emergency preparedness for
      identification of regions enriched with frail individuals.

PMID- 28437321
TI  - Medical Expenditures Associated With Diabetes Among Youth With Medicaid Coverage.
AB  - BACKGROUND: Information on diabetes-related excess medical expenditures for youth
      is important to understand the magnitude of financial burden and to plan the
      health care resources needed for managing diabetes. However, diabetes-related
      excess medical expenditures for youth covered by Medicaid program have not been
      investigated recently. OBJECTIVE: To estimate excess diabetes-related medical
      expenditures among youth aged below 20 years enrolled in Medicaid programs in the
      United States. METHODS: We analyzed data from 2008 to 2012 MarketScan multistate
      Medicaid database for 6502 youths with diagnosed diabetes and 6502 propensity
      score matched youths without diabetes, enrolled in fee-for-service payment plans.
      We stratified analysis by Medicaid eligibility criteria (poverty or disability).
      We used 2-part regression models to estimate diabetes-related excess medical
      expenditures, adjusted for age, sex, race/ethnicity, year of claims, depression
      status, asthma status, and interaction terms. RESULTS: For poverty-based Medicaid
      enrollees, estimated annual diabetes-related total medical expenditure was $9046
      per person [$3681 (no diabetes) vs. $12,727 (diabetes); P<0001], of which 41.7%,
      34.0%, and 24.3% were accounted for by prescription drugs, outpatient, and
      inpatient care, respectively. For disability-based Medicaid enrollees, the
      estimated annual diabetes-related total medical expenditure was $9944 per person
      ($14,149 vs. $24,093; P<0001), of which 41.5% was accounted for by prescription
      drugs, 31.3% by inpatient, and 27.3% by outpatient care. CONCLUSIONS: The per
      capita annual diabetes-related medical expenditures in youth covered by publicly
      financed Medicaid programs are substantial, which is larger among those with
      disabilities than without disabilities. Identifying cost-effective ways of
      managing diabetes in this vulnerable segment of the youth population is needed.

PMID- 28437322
TI  - Double Lumen Polyamide Tube-stent for the Treatment of Recurrent Postcorrosive
      Esophageal Stenosis.
AB  - This article presents the results of endoscopic treatment for recurrent
      postcorrosive esophageal stenosis with a tube-stent developed at our institution.
      The tube-stent was implanted in 5 children with corrosive esophageal injury at
      the age of 2 to 8.5 years after 7 to 64 dilatation sessions during 5 to 118
      months. In total, 13 tube-stents were implanted. One patient had undergone 9
      procedures during 2.5 years and the tube-stent remained in place for 14 to 250
      days. This patient was tube-stent-dependent due to the lack of any possibility of
      surgical reconstruction. Two patients had the tube-stent removed after 150 to 205
      days and they remain free from esophageal restenosis. One patient did not
      tolerate the tube-stent, evacuated it after 1 day and was referred for surgical
      esophagus replacement. One patient is currently still being treated with the tube
      stent. Tube-stent was well tolerated and it may be effective in children with
      recurrent critical postcorrosive esophageal stenosis.

PMID- 28437323
TI  - Lack of Utility of Anti-tTG IgG to Diagnose Celiac Disease When Anti-tTG IgA Is
      Negative.
AB  - OBJECTIVES: Guidelines for diagnosing celiac disease (CD) recommend initial
      testing with a highly sensitive serologic test for anti-tissue transglutaminase
      immunoglobulin A antibodies (tTG IgA). When the probability of CD is high, IgA
      deficiency should be considered. The 2 approaches to address this include
      measuring "both tTG IgA and tTG IgG" or measuring "total IgA." We aim to assess
      the utility of an isolated positive tTG IgG result in diagnosing CD. METHODS: We
      conducted a retrospective review of patients undergoing serologic testing for CD
      from January 1997 to June 2014. Patients with positive tTG IgG and negative tTG
      IgA were included. Moreover, all patients who had any other positive CD-specific
      serologic findings were excluded. Demographics, clinical presentation, tests, and
      biopsy results were recorded. RESULTS: The indication for checking celiac
      serology was gastrointestinal symptoms in 172 of 233 patients, iron deficiency
      anemia in 12, and high-risk screening in 48. Small bowel biopsy was performed in
      178 patients (77%); 160 had normal results and 18 had histologic changes
      suggestive of enteropathy. Nine patients had increased intraepithelial
      lymphocytes, and 9 had partial villous atrophy. Only 6 cases of CD were, however,
      confirmed. The utility of isolated tTG IgG in diagnosis of CD was low at 3%
      (6/178). CONCLUSION: In this cohort of patients, the utility of isolated tTG IgG
      in diagnosing CD was low at 3%.

PMID- 28437324
TI  - Noncirrhotic Portal Fibrosis in Pediatric Population.
AB  - OBJECTIVES: Noncirrhotic portal fibrosis (NCPF) has been classically described as
      a disease of young to middle age with limited literature regarding its
      occurrence, onset, or clinical presentation in children. We hereby present a
      series of 19 patients diagnosed and managed as NCPF in pediatric age group.
      METHODS: A retrospective review of all the patients presenting to the pediatric
      hepatology department (age <18 years) and diagnosed as NCPF was done and data
      were evaluated. RESULTS: A total of 19 patients were diagnosed as NCPF with
      median age at onset of symptoms and diagnosis as 10 years and 13.8 years
      respectively. Majority presented with left upper quadrant discomfort or mass.
      Laboratory parameters showed hypersplenism in majority with preserved liver
      synthetic functions. Median values for hepatic venous pressure gradient and liver
      stiffness measurement were 13.5 mmHg and 10.6 kPa, respectively. Classical
      hepatic histopathological features seen were maintained lobular architecture,
      atretic portal tracts, approximation of portal-portal and portal-central areas,
      and aberrant peripheral portal channels. During follow-up, majority of the
      patients did not show disease progression. CONCLUSIONS: NCPF is not an uncommon
      entity in pediatric population with age of onset in early second decade. Hepatic
      histopathology must be used to exclude cirrhosis and to confirm the diagnosis.
      Hepatic venous pressure gradient and liver stiffness measurement values, in some
      cases, may overlap with those in patients with cirrhosis and may not be
      diagnostic in isolation. Any patient presenting with evidence of portal
      hypertension with preserved hepatic functions, irrespective of the age, should be
      evaluated for possible NCPF.

PMID- 28437325
TI  - Presenting Features and Prognosis of Ischemic and Nonischemic Neonatal Liver
      Failure.
AB  - OBJECTIVES: To describe the epidemiological features, clinical characteristics
      and outcomes of neonates diagnosed with liver failure, as well as determine
      prognostic factors. METHODS: Cohort study conducted at a single tertiary referral
      and university-affiliated pediatric center. Hospital records of all neonates
      diagnosed with liver failure between January 2003 and December 2015 were
      retrospectively reviewed, and data on clinical and laboratory findings,
      treatment, and outcomes were collected. Survival analysis (Kaplan-Meier) and Cox
      regression were performed to identify prognostic factors at diagnosis. Liver
      failure diagnosis was established using the pediatric acute liver failure study
      group's diagnostic criteria for every patient with coagulopathy and biochemical
      pattern of liver disease. RESULTS: Forty-five patients were included. In our
      series, most cases were secondary to ischemia (28.9%). Other causes were neonatal
      hemochromatosis (17.8%), viral infections (13.3%), and inborn errors of
      metabolism (13.3%). A total 55.6% (25/45) of the patients died (median age: 16
      days; range 1-235 days). Alanine aminotransferase (ALT) at diagnosis was
      associated with higher mortality or the need for liver transplantation on day 21
      after diagnosis (P = .006). For every 500 IU/L increase in ALT serum levels, the
      mortality/liver transplantation rate increased 1.3 times (hazard ratio 95%
      confidence interval: 1.1-1.6). Although ischemic neonatal acute liver failure
      presents with higher ALT levels, these cases appear to have better outcomes.
      Higher international normalized ratio tended to increase
      mortality/transplantation (hazard ratio 1.02; 95% confidence interval 0.91-1.2).
      CONCLUSIONS: Neonatal liver failure should perhaps be considered in the
      differential diagnoses of any coagulopathy. ALT and international normalized
      ratio levels at diagnosis could predict prognosis in the short term. Ischemic
      liver failure appears to have a better prognosis.

PMID- 28437327
TI  - A New Partnership: The Need for Greater Collaboration and Integration.

PMID- 28437326
TI  - Favorable Outcomes of Preterm Infants With Parenteral Nutrition-associated Liver
      Disease Treated With Intravenous Fish Oil-based Lipid Emulsion.
AB  - OBJECTIVES: The aim of the study was to determine the acute and long-term
      outcomes of preterm infants treated with an intravenous fish oil-based lipid
      emulsion (FishLE) for parenteral nutrition-associated liver disease (PNALD).
      METHODS: Preterm infants 14 days to 24 months of age with anatomic short gut or
      severe intestinal dysmotility, serum direct bilirubin >=4 mg/dL, and requiring
      >60% calories from parenteral nutrition were eligible. Enrolled infants received
      1 g . kg . day of FishLE until resolution of direct hyperbilirubinemia or return
      of enteral nutrition. Acute clinical effects and biochemical markers of liver
      function were monitored. Growth and developmental scores at 6 and 12 months
      postmenstrual age (PMA) were assessed and compared with controls matched by
      gestational age (GA). RESULTS: Thirteen patients with mean GA of 28 +/- 4 weeks
      were treated and compared with 119 GA-matched controls. Their mean direct
      bilirubin was 9.8 +/- 6.4 mg/dL at enrollment. All infants had resolution of
      cholestasis after study completion. There were no acute adverse events, deaths,
      or liver/intestinal transplants. Weight and head circumference were similar
      between FishLE-treated patients and controls at 6- and 12-month PMA. Cognitive
      and motor scores were decreased at 6 and 12 months PMA in FishLE-treated infants.
      Logistic regression analysis showed that prolonged hospitalization was
      detrimental to cognitive and motor development, whereas treatment was not.
      CONCLUSIONS: The use of intravenous FishLEs in premature infants appears to be
      safe and reverses PNALD despite significant liver disease and intestinal failure.
      This therapy should be used in preterm infants with PNALD and followed long term
      to evaluate development.

PMID- 28437328
TI  - Is An Isolated Intervertebral Disk With Significant Degeneration Magnetic
      Resonance Imaging A Cause of Low Back Pain That Requires No Confirmatory
      Diagnostic Tests?

PMID- 28437329
TI  - Metastatic Spinal Cord Compression and Steroid Treatment: A Systematic Review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: We conducted a systematic review of
      the literature to answer the following questions regarding the use of steroid
      therapy in metastatic spinal cord compression (MSCC): 1. In cases of MSCC, what
      is the effect of steroid administration before definitive radiotherapy or surgery
      on ambulatory status, bowel and bladder function and survival? 2. What steroid
      dosing regimens are associated with the best outcomes concerning neurological
      symptoms and complication prevention in cases of MSCC? SUMMARY OF BACKGROUND
      DATA: Currently, there is significant variation in the initial bolus dose, daily
      maintenance dose and duration of treatment when steroids are used as a bridge to
      definitive therapy for MSCC. METHODS: A literature search following PRISMA
      guidelines was conducted in June 2016, using Medline via Ovid SP, Medline via
      PubMed, Embase, Biosis Previews and the Cochrane Library. Search terms used in
      each database varied slightly to optimize results. All generic steroid
      formulations were included along with spinal cord compression or myelopathy
      combined with metastatic or malignant tumors. Papers discussing acute traumatic
      causes of spinal cord compression were excluded, as were papers discussing cord
      compression from nonmetastatic tumors or epidural lipomatosis. Subjects were
      limited to adult humans undergoing definitive treatment with radiotherapy or
      surgery. RESULTS: Of the 309 papers retrieved, 66 full text studies were reviewed
      and 6 papers were found to address the stated questions. CONCLUSIONS: There is a
      paucity of high quality literature evaluating the use of steroids in MSCC. On the
      basis of the evidence available an initial 10 mg intravenous bolus of
      dexamethasone followed by 16 mg PO QD has been associated with fewer
      complications compared with 100 mg bolus and 96 mg QD. Weaning of steroids should
      occur rapidly after definitive treatment. Risk of gastric bleeding or perforation
      can be managed with the routine use of proton-pump inhibitors. LEVEL OF EVIDENCE:
      Level IIIa.

PMID- 28437330
TI  - Pedicle Screw Fluid Sign: An Indication on Magnetic Resonance Imaging of a Deep
      Infection After Posterior Spinal Instrumentation.
AB  - STUDY DESIGN: A single-center case-referent study. OBJECTIVE: To assess whether
      the "pedicle screw (PS) fluid sign" on magnetic resonance imaging (MRI) can be
      used to diagnose deep surgical site infection (SSI) after posterior spinal
      instrumentation (PSI). SUMMARY OF BACKGROUND DATA: MRI is a useful tool for the
      early diagnosis of a deep SSI. However, the diagnosis is frequently difficult
      with feverish patients with clear wounds after PSI because of artifacts from the
      metallic implants. There are no reports on MRI findings that are specific to a
      deep SSI after PSI. We found that fluid collection outside the head of the PS on
      an axial MRI scan (PS fluid sign) strongly suggested the possibility of an
      abscess. METHODS: The SSI group comprised 17 patients with a deep SSI after
      posterior lumbar spinal instrumentation who had undergone an MRI examination at
      the onset of the SSI. The non-SSI group comprised 64 patients who had undergone
      posterior lumbar spinal instrumentation who did not develop an SSI and had an MRI
      examination within 4 weeks after surgery. The frequency of a positive PS fluid
      sign was compared between both groups. RESULTS: The PS fluid sign had a
      sensitivity of 88.2%, specificity of 89.1%, positive predictive value of 68.1%,
      and negative predictive value of 96.6%. The 2 patients with a false-negative PS
      fluid sign in the SSI group had an infection at the disk into which the interbody
      cage had been inserted. Three of the 7 patients with a false-positive PS fluid
      sign in the non-SSI group had a dural tear during surgery. CONCLUSIONS: The PS
      fluid sign is a valuable tool for the early diagnosis of a deep SSI. The PS fluid
      sign is especially useful for diagnosing a deep SSI in difficult cases, such as
      feverish patients without wound discharge.

PMID- 28437331
TI  - Do the Position and Orientation of the Crosslink Influence the Stiffness of
      Spinal Instrumentation?
AB  - STUDY DESIGN: Biomechanical study of double-level pedicle screw constructs with
      or without crosslinks (CL) in an unstable model. OBJECTIVES: The purpose of this
      study is to investigate the optimal position and orientation of the CL. SUMMARY
      OF BACKGROUND DATA: Several reports have described biomechanical research on such
      CL, but no definite consensus has been reached regarding the effects. Very few
      studies have examined the position and orientation of the CL. The question of
      where and how the CL should be clinically set remains unanswered. METHODS: Ten
      cadaveric lumbar spines (L3-L5) of boars were used and 7 models were prepared by
      the sequential damage and spinal instrumentation of each specimen. Bending
      stiffness was measured in flexion, extension, lateral bending, and axial rotation
      for each model using 6-axis material tester under torque of 0 to +/-3 N m.
      Results for each configuration were compared using analysis of variance and the
      Turkey-Kramer test. RESULTS: In flexion, extension, and lateral bending, 7 models
      showed similar stiffness with no significant differences. In axial rotation,
      stiffness increased significantly (P<0.05) in the cephalic, central, caudal, and
      oblique CL models in comparison with that of the no CL model, and stiffness of
      the horizontal 2 CL and oblique 2 CL models was significantly higher than that of
      cephalic, central, caudal, and oblique CL models (P<0.05). However, no
      significant differences in stiffness were seen between cephalic, central, and
      caudal CL models, between the central and oblique CL models, or between the
      horizontal and oblique 2 CL models. CONCLUSIONS: Concomitant use of CLs
      significantly increased axial rotational stiffness, even though stiffness in
      flexion, extension, and lateral bending was not increased. In addition, stiffness
      in axial rotation significantly improved with the use of 2 CLs instead of a
      single CL, and stiffness was unchanged by position and orientation of CL.

PMID- 28437332
TI  - Ultrasound Assessment of the Abdominal Muscles at Rest and During the ASLR Test
      Among Adolescents With Scoliosis.
AB  - STUDY DESIGN: Observational study. OBJECTIVE: Are there deviations in the
      thickness of abdominal muscles at rest in individuals with adolescent idiopathic
      scoliosis (AIS)? Are there deviations in abdominal muscular activity in people
      with AIS during the active straight leg raise (ASLR) test? SUMMARY OF BACKGROUND
      DATA: Ultrasound imaging can be used to assess the lateral abdominal muscle. Some
      authors suggest that scoliosis develops through a weakness or improper
      functioning of the abdominal muscles that cannot provide adequate support to the
      spinal segments. However, the literature lacks studies on the functioning of the
      abdominal muscles in individuals with spinal deviations. This study focuses on
      the evaluation of the thickness of the external oblique (EO), internal oblique
      (IO), and transversus abdominalis (TrA) muscles of individuals with AIS.
      MATERIALS AND METHODS: Seventy-one healthy adolescents and 71 patients with AIS,
      all aged 10-16 years, were studied. The thickness of the muscles at rest was
      measured at the end of normal exhalation in millimeters. Muscular activity during
      the ASLR test was measured in the final position, and the standards were
      normalized with the thickness produced at rest. Muscular activity during the ASLR
      test was represented as a percentage change in the muscle thickness. RESULTS: The
      AIS group demonstrated a smaller resting thickness of all tested muscles of both
      sides (P<0.01). All the muscles on the right side of the body showed higher
      activity in the AIS group during the ASLR test (P<0.01). CONCLUSIONS: Patients
      with AIS had thinner EO, IO, and TrA at rest in the supine position. During the
      ASLR test, the AIS patients displayed higher activity of the EO, IO, and TrA
      muscles on the right side.

PMID- 28437333
TI  - Correction Capability in the 3 Anatomic Planes of Different Pedicle Screw Designs
      in Scoliosis Instrumentation.
AB  - STUDY DESIGN: Computer simulations to compare the correction capabilities of
      different pedicle screws in adolescent idiopathic scoliosis (AIS)
      instrumentations. OBJECTIVE: To compare the correction and resulting bone-screw
      forces associated with different pedicle screws in scoliosis instrumentations.
      SUMMARY OF BACKGROUND DATA: Pedicle screw fixation is widely used in surgical
      instrumentation for spinal deformity treatment. Screw design, correction
      philosophies, and surgical techniques are constantly evolving to achieve better
      control of the vertebrae and correction of the spinal deformity. Yet, there
      remains a lack of biomechanical studies that quantify the effects and advantages
      of different screw designs in terms of correction kinematics. METHODS: The
      correction capabilities of fixed-angle, multiaxial, uniaxial, and saddle axial
      screws were kinematically analyzed, simulated, and compared. These simulations
      were based on the screw patterns and correction techniques proposed by 2
      experienced surgeons for 2 AIS cases. Additional instrumentations were assessed
      to compare the correction and resulting bone-screw forces associated with each
      type of screw. RESULTS: The fixed-angle, uniaxial and saddle axial screws had
      similar kinematic behavior and performed better than multiaxial screws in the
      coronal and transverse planes (8% and 30% greater simulated corrections,
      respectively). Uniaxial and multiaxial screws were less effective than fixed
      angle and saddle axial screws in transmitting compression/distraction to the
      anterior spine because of their sagittal plane mobility between the screw head
      and shank. Only the saddle axial screws allow vertebra angle in the sagittal
      plane to be independently adjusted. CONCLUSIONS: Pedicle screws of different
      designs performed differently for deformity corrections or for compensating screw
      placement variations in different anatomic planes. For a given AIS case, screw
      types should be determined based on the particular instrumentation objectives,
      the deformity's stiffness and characteristics so as to make the best of the screw
      designs.

PMID- 28437334
TI  - A New Fixation Technique for French-Door Cervical Laminoplasty: Surgical Results
      With a Minimum Follow-up of 6 Years.
AB  - DESIGN: A case series of 5 patients with multilevel cervical myelopathy treated
      by French-door cervical laminoplasty (FDCL) and use of unicortical iliac crest
      graft as spacer fixed with titanium miniplates and screws is described.
      OBJECTIVE: To report a minimum of 6-year follow-up results of our new plate-screw
      fixation technique for FDCL. SUMMARY OF BACKGROUND DATA: Hardware-assisted
      laminoplasty has the potential advantage of preventing restenosis by holding the
      laminar door "open" while healing progresses and also prevents spacer
      dislodgement. The use of titanium miniplates as internal fixation device for FDCL
      by our novel technique has not been reported. METHODS: Five patients suffering
      from multilevel cervical myelopathy harboring constitutionally narrow cervical
      canal (3) and multilevel cervical spondylotic myelopathy (2) who underwent 2-3
      level FDCL and followed up prospectively for 6 years is presented. Modified
      Kurokawa and colleague's technique of FDCL was performed and autologous iliac
      crest bone graft was interposed between the sagittaly split spinous processes. A
      12- to 15-hole titanium miniplate was contoured into a trapezoidal shape to sit
      flush with the posterior elements. The plate was anchored to bone graft and
      posterior elements with screws and patients mobilized without any external
      orthosis. RESULTS: The mean follow-up was 90.5 months. The mean improvement in
      Neck disability index at final follow-up was 35% and mean improvement in Visual
      analog scale was 4 points. Japanese orthopaedic association score improved from a
      mean of 10 to a mean of 14.8 postoperatively. The final outcome was good (3) and
      excellent (2) by Odom's criteria. All patients improved to Nurick's grade 0 or I
      and reported significant relief from their myelopathic symptoms and axial neck
      pain. There were no postoperative hardware-related complications or
      pseudoarthrosis. CONCLUSIONS: Titanium miniplates are excellent devices for
      stabilizing the interspinous spacers used in FDCL. They prevent cervical canal
      deformation, restenosis, spacer dislodgement and are durable, cost-effective in
      facilitating early mobilization at intermediate-term follow-up of 6 years.

PMID- 28437335
TI  - Do Lordotic Cages Provide Better Segmental Lordosis Versus Nonlordotic Cages in
      Lateral Lumbar Interbody Fusion (LLIF)?
AB  - STUDY DESIGN: A retrospective comparative radiographic review. OBJECTIVE: To
      evaluate the radiographic changes brought about by lordotic and nonlordotic cages
      on segmental and regional lumbar sagittal alignment and disk height in lateral
      lumbar interbody fusion (LLIF). SUMMARY OF BACKGROUND DATA: The effects of cage
      design on operative level segmental lordosis in posterior interbody fusion
      procedures have been reported. However, there are no studies comparing the effect
      of sagittal implant geometry in LLIF. METHODS: This is a comparative radiographic
      analysis of consecutive LLIF procedures performed with use of lordotic and
      nonlordotic interbody cages. Forty patients (61 levels) underwent LLIF. Average
      age was 57 years (range, 30-83 y). Ten-degree lordotic PEEK cages were used at 31
      lumbar interbody levels, and nonlordotic cages were used at 30 levels. The
      following parameters were measured on preoperative and postoperative radiographs:
      segmental lordosis; anterior and posterior disk heights at operative level;
      segmental lordosis at supra-level and subjacent level; and overall lumbar (L1-S1)
      lordosis. Measurement changes for each cage group were compared using paired t
      test analysis. RESULTS: The use of lordotic cages in LLIF resulted in a
      significant increase in lordosis at operative levels (2.8 degrees; P=0.01),
      whereas nonlordotic cages did not (0.6 degrees; P=0.71) when compared with
      preoperative segmental lordosis. Anterior and posterior disk heights were
      significantly increased in both groups (P<0.01). Neither cage group showed
      significant change in overall lumbar lordosis (lordotic P=0.86 vs. nonlordotic
      P=0.25). CONCLUSIONS: Lordotic cages provided significant increase in operative
      level segmental lordosis compared with nonlordotic cages although overall lumbar
      lordosis remained unchanged. Anterior and posterior disk heights were
      significantly increased by both cages, providing basis for indirect spinal
      decompression.

PMID- 28437336
TI  - Both Bilateral Breast Volume Discrepancy and Asymmetric Anterior Chest Wall Shape
      Contribute to the Unsightly Breast Contour in Female Right Thoracic Idiopathic
      Scoliosis.
AB  - STUDY DESIGN: A retrospective radiographic study. OBJECTIVE: To evaluate the
      asymmetry of breast volume (BV) and shape in female adolescent idiopathic
      scoliosis (AIS) patients and to define their relationship with deformed
      components of the anterior chest wall and curved spine. SUMMARY OF BACKGROUND
      DATA: The higher incidence of asymmetric breast development in AIS was described
      by prior studies. However, the interplay between scoliosis curve magnitude and
      severity of breast asymmetry (BA) are unknown. METHODS: A total of 73 surgically
      treated female right thoracic AIS patients classified as Lenke type I were
      enrolled in this study, with the average Cobb angle being 52.08+/-11.68 degrees.
      The Image J software was utilized to calculate BV. Both concave and convex
      radiographic parameters of breast shape were measured including the extraversion
      angle (EA), the coverage angle (CA), the axial breast height, the vertical breast
      height (VBH), and the nipple-to-sternum distance. The inclination angles of the
      concave and convex anterior chest wall were also assessed. BA was calculated
      according to the formula as follows: BA=(concave
      convex)*BV/[(concave+convex)*BV]/2. The measurements of spinal deformity
      parameters included the Cobb angle, the RAsag angle, and the RAml angle. Paired t
      test was performed to analyze the asymmetry of breast shape, and Pearson
      correlation analysis was utilized to define the correlation between the breast
      shape, spinal deformity, and the inclination of anterior chest wall. RESULTS: The
      concave BV, EA, axial breast height, and vertical breast height were
      significantly larger than those of the convex side (P<0.05), whereas the concave
      CA and the inclination angle of the anterior chest wall were significantly
      smaller than those of the convex side (P<0.05). No difference was detected
      between the concave and the convex nipple-to-sternum distance (P>0.05). The
      averaged BA was 11.4%, with the ratio of asymmetry beyond 10% being 52.1%. No
      statistically significant relationships between BA and Cobb angle, RAsag angle,
      RAml angle were detected (P>0.05). The inclination angle of the anterior chest
      wall demonstrated significant correlation with EA (P<0.001) and CA (P<0.001),
      respectively. CONCLUSIONS: The incidence of BA in AIS is notable, with the
      concave breast being larger, more extroversive, and more concentrated than the
      convex breast. The discrepancy between concave and convex anterior chest wall
      inclination bound to scoliosis could have a major influence on breast orientation
      and profile, suggesting a synergistic role of anterior chest wall deformity and
      bilateral BV discrepancy in the formation of BA.

PMID- 28437337
TI  - Axial Plane Deformity of the Shoulder in Adolescent Idiopathic Scoliosis.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: To study axial plane
      deformation of the shoulder in adolescent idiopathic scoliosis (AIS) and try to
      correlate it with curve type and surgical correction. SUMMARY OF BACKGROUND DATA:
      It is established that AIS is a 3-dimensional deformity. The rib hump is the most
      common manifestation of axial plane deformations; the least common manifestation
      seems to be upper trunk and shoulder rotation, which has been hitherto
      undescribed. METHODS: Fourteen consecutive, operated cases of AIS were analyzed
      prospectively. Preoperative and postoperative x-rays of the spine and clinical
      photographs were studied. Clinical photographs (top view) were taken with
      patients in the sitting position, to show shoulder level in relation to the axis
      of the head and pelvis. Chest computed tomography scans were also studied to
      determine the direction of apical vertebra and trunk torsion. RESULTS: All 14
      patients in this series had their right shoulders anteriorly rotated
      preoperatively (anticlockwise). The direction of rotation seemed unrelated to the
      curve type and shoulder elevation, although most had rib humps on the right. This
      shoulder rotation was corrected postoperatively by routine maneuvers done for
      scoliosis correction. Minor residual rotation was seen in 6 patients who also had
      minimal persisting rib hump. In 1 case the axial plane rotation worsened,
      although the shoulder level and trunk symmetry improved significantly. The apical
      vertebral rotation on computed tomography had little bearing on the direction of
      shoulder rotation. CONCLUSIONS: Axial plane rotation of the shoulder is a
      hitherto un-described dimension of AIS deformity complex. Much of it corrects
      spontaneously with correction of the thoracic spinal deformity.

PMID- 28437338
TI  - Ponte Osteotomy During Dekyphosis for Indirect Posterior Decompression With
      Ossification of the Posterior Longitudinal Ligament of the Thoracic Spine.
AB  - STUDY DESIGN: Retrospective clinical study. PURPOSE: To investigate the outcomes
      after indirect posterior decompression and dekyphosis using multilevel Ponte
      osteotomies for ossification of the posterior longitudinal ligament (OPLL) of the
      thoracic spine. SUMMARY OF BACKGROUND DATA: There are no previous reports on the
      use of Ponte osteotomy to treat thoracic OPLL. METHODS: The subjects were 10
      patients with an average age at surgery of 47 years, who underwent indirect
      posterior decompression and dekyphosis using multilevel Ponte osteotomies at our
      institute. Minimum follow-up period was 2 years, and averaged 2 year 6 months.
      Using radiographs and CT images, we investigated fusion range, preoperative and
      postoperative Cobb angles of thoracic fusion levels, intraoperative
      ultrasonography, and clinical results. RESULTS: The mean fusion area was 9.8
      vertebraes, with average laminectomy of 7.3 laminas. The mean preoperative
      thoracic kyphosis of fusion levels on standing radiograph measured 35 degrees and
      was changed to 21 degrees after surgery. The mean number of Ponte osteotomies was
      3 levels. The mean preoperative and postoperative (at the 1 y follow-up) JOA
      scores were 3.5 and 7.5 points, respectively, and the recovery rate was 56%. On
      intraoperative ultrasonography, 7 of the cases were included in the floating (+)
      and 3 in the floating (-) groups, and the recovery rates were 66.0% and 33.4%,
      respectively. CONCLUSIONS: "The Ponte procedure for indirect spinal cord
      decompression" is a novel concept used for the first time with thoracic OPLL in
      our study, and we consider it a useful method to achieve more effectively
      dekyphosis and indirect spinal cord decompression if there is not the spinal cord
      free from OPLL on intraoperative ultrasonography after only laminectomies.

PMID- 28437339
TI  - A Multicenter Evaluation of Clinical and Radiographic Outcomes Following High
      grade Spondylolisthesis Reduction and Fusion.
AB  - OBJECTIVE: A retrospective review of the clinical and radiographic outcomes from
      a multicenter study of surgical treatment for high-grade spondylolisthesis (HGS)
      in adults. The objective was to assess the safety of surgical reduction, its
      ability to correct regional deformity, and its clinical effectiveness. METHODS:
      Retrospective, multicenter review of adults (age above 18 y) with lumbosacral HGS
      (Meyerding grade 3-5) treated surgically with open decompression, attempted
      reduction, posterior instrumentation, and interbody fusion. Preoperative and
      postoperative assessment of the Meyerding grade, slip angle, and sacral
      inclination were performed based on standing radiographs. Preoperative visual
      analog scale scores were compared with those at the mean follow-up period. Prolo
      and Oswestry Disability Index scores at most recent follow-up were assessed.
      RESULTS: A total of 25 patients, aged 19-72 years, met inclusion criteria.
      Seventeen interbody cages were placed, including 15 transforaminal lumbar
      interbody fusions, 1 posterior lumbar interbody fusion, and 1 anterior lumbar
      interbody fusion. Five patients required sacral dome osteotomies. The average
      follow-up was 21.3 months.At most recent follow-up there was a statistically
      significant improvement in both the Meyerding grade and the slip angle (P<0.05).
      There was 1 intraoperative complication resulting in a neurological deficit (4%)
      and 1 intraoperative vertebral body fracture (4%). No additional surgery was
      required for any of these patients. There were no cases of nonunion or device
      failure except for 1 patient who suffered an unrelated traumatic injury 1 year
      after surgery. The mean Oswestry Disability Index and Prolo scores at mean follow
      up of 21.3 months were 20% (minimum disability) and 8.2 (grade 1), respectively.
      CONCLUSIONS: The present study suggests that reduction, when accomplished in
      conjunction with wide neural element decompression and instrumented arthrodesis,
      is safe, effective, and durable with low rates of neurological injury, favorable
      clinical results, and high-fusion rates.

PMID- 28437340
TI  - Proximal Junctional Kyphosis Following Posterior Hemivertebra Resection and Short
      Fusion in Children Younger Than 10 Years.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate whether proximal
      junctional kyphosis (PJK) or obvious proximal junctional angle (PJA) changes in
      the sagittal plane develops following short fusion in children younger than 10
      years of age with congenital scoliosis, and to investigate the possible risk
      factors. SUMMARY OF BACKGROUND DATA: PJK following long spinal fusion in
      adolescents and adults is a serious postoperative complication. Although the same
      problem may occur in patients with early-onset scoliosis who have undergone spine
      fusion, few studies have been reported any relationship between PJK and spinal
      fusion in young children with congenital scoliosis. MATERIALS AND METHODS: Thirty
      seven children treated in a single institution between 1998 and 2010 were
      reviewed retrospectively. The inclusion criteria included (1) younger than 10
      years of age at the time of operation; (2) simple congenital deformity; (3)
      hemivertebra treated by posterior hemivertebrectomy with short fusion at a
      maximum of 5 motion segments; and (4) minimum follow-up for 2 years. The PJA from
      the caudal endplate of the upper instrumented vertebra (UIV) to the cephalad
      endplate of the vertebra adjacent to the UIV, thoracic kyphosis (T5-T12), lumbar
      lordosis (T12-S1), global sagittal balance, and magnitude of scoliosis of the
      major curves and upper compensated curves were measured on lateral radiographs.
      PJK was defined by a PJA>10 degrees during the follow-up and at least 10 degrees
      greater than the preoperative or early postoperative measurement. Wilcoxon tests
      were performed for statistical analysis. RESULTS: PJK occurred in 7 of 37
      patients (18.9%), during an average of 4.5+/-3.2 years of follow-up (2-12 y). The
      UIV level of children with PJK was on T9 in 4 patients, and T11, T12, and L1 in
      1. Screw malposition at UIV was confirmed by postoperative computed tomography
      images in 6 patients. Only 1 patient with a screw deviation did not develop PJK
      during the follow-up period. None of the patients with PJK was symptomatic, and
      no patients required revision surgery because of PJK. PJK occurred and progressed
      during the first 6 months after surgery followed by almost no progression or
      slight improvement in patients that could be followed up beyond 6 months
      postoperatively; in association with an increase of the lumbar lordosis.
      CONCLUSIONS: PJK occurred in pediatric patients with simple congenital
      deformities following hemivertebrectomy and short fusion. PJK was more common in
      patients with (1) greater immediately postoperative segmental kyphosis and PJA;
      (2) screw malposition on the UIV; and (3) hemivertebra located on the lower
      thoracic or the thoracolumbar region.

PMID- 28437341
TI  - Measurement of Thoracic Inlet Alignment on MRI: Reliability and the Influence of
      Body Position.
AB  - STUDY DESIGN: A retrospective radiographic study. OBJECTIVE: To investigate the
      reliability of using magnetic resonance imaging (MRI) to measure thoracic outlet
      parameters and whether supine MRI could supersede upright x-ray in measuring
      these parameters. SUMMARY OF BACKGROUND DATA: On x-ray, overlapped soft and bony
      tissues make sternum contour invisible. Thus, measuring thoracic inlet (TI)
      alignment on x-ray may be inaccurate. MRI could clearly show anatomy around TI.
      METHODS: A total of 124 adolescents with idiopathic thoracolumbar/lumbar
      scoliosis were recruited. The visibility of T1 upper endplate and the upper end
      of sternum on the lateral standing x-ray films was rated. For patients with
      moderate or good clarity forT1 upper endplate and the upper end of sternum on x
      ray films, thoracic inlet angle (TIA), T1 slope (T1S), and neck tilt (NT) were
      measured by 3 observers on standing x-ray films and supine MR images,
      respectively. Intraclass correlation coefficients (ICC) were used to determine
      the intraobserver, interobserver, and method reliability. The paired t test was
      performed to compare the measurements between the 2 methods. The correlation
      coefficients between the 2 methods were analyzed by regression analysis. RESULTS:
      The visibility of TI region on x-ray films was unsatisfactory, whereas all the
      landmarks were clear on MR images. Only 81 patients' x-ray films were graded as
      moderate or good visibility in the TI region. Both the intraobserver ICC and
      interobserver ICC were better in the MRI set than in the x-ray set among all the
      observers for 3 TI parameters. The paired t test demonstrated that no significant
      difference was noted in terms of TIA, T1S, and NT (P=0.572, 0.203, and 0.637,
      respectively). Regression analysis demonstrated high correlation coefficients for
      TIA, T1S, and NT (R=0.612, 0.629, and 0.722, respectively). CONCLUSIONS: MRI
      serves as a good substitute for x-ray scans with regard to the measurement of TI
      alignment, with superior reliability.

PMID- 28437342
TI  - Left Ventricular Mechanics Assessed by 2-dimensional Speckle Tracking
      Echocardiography in Children and Adolescents With Idiopathic Scoliosis.
AB  - STUDY DESIGN: A retrospective review of data collected prospectively. OBJECTIVE:
      The study aimed to assess the possible effects of idiopathic scoliosis on left
      ventricular (LV) myocardial performance in children and adolescent patients.
      SUMMARY OF BACKGROUND DATA: Spine anomaly may impair cardiorespiratory function.
      It has been confirmed that respiratory function decreased in patients with
      scoliosis. However, limited study of the effect of scoliosis on heart function
      has been published, and no assessment of myocardial deformation of these patients
      has been reported to our knowledge. METHODS: Forty-one patients with a median age
      of 16 years and a median Cobb's angle of 75 degrees were studied. LV myocardial
      deformation was evaluated using 2-dimensional speckle-tracking echocardiography.
      The results were compared with those of 33 controls. The correlations between
      Cobb's angle and echocardiographic parameters in patients were also explored.
      RESULTS: Compared with controls, patients had significantly lower global LV
      longitudinal systolic strain in all 3 views (4 chamber, 2 chamber, and 3 chamber
      views), lower global radial and circumferential strains in mitral valve (MV)
      level and papillary muscle (PM) level; reduced LV longitudinal early diastolic
      strain rate (SRe) in all 3 longitudinal views and reduced radial SRe in MV level
      and reduced circumferential SRe in apical (AP) level; decreased LV longitudinal
      late diastolic strain rate in 4-chamber view and decreased radial ones in all 3
      short-axis levels. Among patients, Cobb's angle correlated negatively with LV
      global radial strain of MV level (r=-0.37, P=0.02), global circumferential strain
      of MV level (r=-0.35, P=0.03), and global circumferential strain of PM level (r=
      0.49, P=0.001), whereas positively with LV longitudinal SRa of 4-chamber view
      (r=0.46, P=0.003), longitudinal SRa of 2-chamber view (r=0.49, P=0.001), and
      circumferential SRa of AP level (r=0.35, P=0.02). CONCLUSIONS: LV mechanics are
      impaired in patients with idiopathic scoliosis, which correlate with the severity
      of scoliosis. Our findings suggest the need and provide a mechanical basis for
      further studies in these patients.

PMID- 28437343
TI  - Spinopelvic Alignment by Different Surgical Methods in the Treatment of
      Degenerative Sagittal Imbalance of the Lumbar Spine.
AB  - STUDY DESIGN: A retrospective comparative study. OBJECTIVE: To compare pedicle
      subtraction osteotomy (PSO) and iliac fixation (ILF) without osteotomy as methods
      of correcting lumbar spine deformities due to degenerative sagittal imbalance
      (DSI) through the evaluation of the changes in spinopelvic alignment. SUMMARY OF
      BACKGROUND DATA: Many papers have reported the surgical results after PSO and ILF
      for patients with fixed adult deformities. However, little is known about the
      difference between PSO and ILF corrections of spinopelvic alignment in adults
      with DSI. METHODS: DSI patients who had undergone PSO or ILF with a minimum of 2
      year follow-up (FU) were retrospectively studied in PSO (n=30) or ILF (n=25)
      groups. Lumbar lordosis (LL), thoracic kyphosis (TK), and sagittal vertical axis
      (SVA) were measured as spinal parameters and pelvic incidence (PI), sacral slope
      (SS), and pelvic tilt (PT) were used as measurements of pelvic parameters.
      Clinical outcomes were evaluated using a visual analogue scale (VAS) and Oswestry
      Disability Index (ODI) scores. RESULTS: There were no statistically significant
      differences between the PSO and ILF groups with regard to age and fused segments,
      but there were significant differences in operative time and estimated blood
      loss. Concerning spinal parameters, there were significant increases of LL and TK
      in PSO group immediate postoperatively (LL: P=0.014, TK: P=0.017) and at the 2
      year FU (LL: P=0.021, TK: P=0.022), but no significant difference in SVA was
      evident between the 2 groups. Within the pelvic parameters, there was a
      significant increase of SS and decrease of PT in the ILF group immediate
      postoperatively (SS: P=0.013, PT: P=0.009) and at the 2-year FU (SS: P=0.024, PT:
      P=0.027), but the PI in both groups was not changed after surgery and there was
      no significant difference between 2 groups. VAS and ODI were significantly
      improved after surgery in both groups. CONCLUSIONS: The PSO group was better than
      the ILF group in the correction of the LL and TK, but not with regard to the
      pelvic parameters. The ILF group was superior in the correction of the pelvic
      orientation as compared with the PSO group when the PI was constant after
      surgery. Ultimately, ILF effectively achieves better correction of the pelvic
      parameters (SS and PT).

PMID- 28437344
TI  - Comparison of the Posterior Vertebral Column Resection With the Expandable Cage
      Versus the Nonexpandable Cage in Thoracolumbar Angular Kyphosis.
AB  - STUDY DESIGN: This was a retrospective study. OBJECTIVE: To compare the
      radiographic and clinical results of anterior support with nonexpandable cage
      with those of expandable cage. SUMMARY OF BACKGROUND DATA: The goals of surgical
      treatment in patients with thoracolumbar angular kyphosis are to improve the
      neurological deficit through neural decompression, to restore the normal
      alignment by correction of deformity, and to stabilize the spinal column by
      arthrodesis. Mesh cages have been traditionally used for reconstruction after
      corpectomy. However, expandable cages are gaining popularity due to some
      advantages over mesh cages, structural autograft or allograft, and poly-ether
      ether-ketone/carbon fiber. MATERIALS AND METHODS: We performed a retrospective
      study in a consecutive series of 42 subjects with a male-to-female ratio of
      15:27, a mean age of 65.3+/-10.9 years, and a mean follow-up period of 36.4+/-7.1
      months, who underwent posterior vertebral column resection at our medical
      institutions between 2006 and 2011. They consist of 32 patients with
      posttraumatic kyphosis with a mean kyphotic angle of 33.1 degrees (range, 12.2
      58.1 degrees) and 10 patients with tuberculous kyphosis with a mean kyphotic
      angle of 53.9 degrees (range, 22.6-126.0 degrees). The mean follow-up period was
      36.4 months (range, 28-54 mo). We compared the clinical outcomes between the 2
      groups based on radiographic findings, neurological status, and complications.
      Intervertebral heights and kyphosis at the level of vertebral column resection
      were used to measure the radiographic outcomes. Neurological outcome was
      evaluated using the modified Frankel grading system. RESULTS: Postoperatively,
      the mean kyphosis angle was 3.0+/-10.8 and 6.7+/-7.2 degrees (P=0.094). At a
      final follow-up, these values were 4.7+/-10.1 and 12.3+/-18.9 degrees in the
      corresponding order (P=0.099). There were 19 (80.0%) and 21 (86.4%) patients with
      solid arthrodesis of grade 1. On modified Frankel grading system, all the
      patients but one achieved improvement. But there was no significant difference in
      the grade between the 2 groups (P>0.05). Also in our series, there were 12
      patients with cage subsidence and 6 with screw loosening. CONCLUSIONS:
      Nonexpandable cage and expandable cage are viable options for anterior support;
      both cages allow for correction of kyphosis with good fusion rate with similar
      neurological outcomes. Expandable cage is effective for the anterior support of
      posterior vertebral column resection.

PMID- 28437345
TI  - Accuracy of Iliac Screws Insertion in Adult Spinal Deformity Surgery:
      Relationship Between Misplacement and the Iliac Morphologies.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the accuracy of
      freehand iliac screw insertion and to determine how this can be performed safely.
      BACKGROUND AND METHODS: Seventy-seven adult scoliosis patients with an average
      age of 70.1 years who underwent spinal deformity surgery with spinopelvic
      fixation using bilateral iliac screws were enrolled. Penetration of the iliac
      table was assessed using postoperative computed tomography. Screw penetration of
      the iliac table or screw insertion from the sacroiliac joint was considered
      misplacement. Screw positioning was classified as the screw being in the proper
      position (group C), the screw penetrating the outer table (group O), and the
      screw penetrating the inner table (group I). The iliac opening angle and the
      distance between the posterior superior iliac spines (PSISs) were measured using
      preoperative computed tomography. The angle between the sacral slope and the
      iliac screw, termed as the sagittal screw angle, was measured using postoperative
      lateral lumbar radiography. RESULTS: Of the 154 iliac screws in 77 patients, 14
      screws in 12 patients penetrated the outer table and 12 screws in 11 patients
      penetrated the inner table. The total proportion of misplacement was 18.8%,
      although there were no major complications. With regard to iliac morphology, the
      iliac opening angle was 24.2+/-4.3 degrees and the distance between the PSISs was
      90.6+/-7.7 mm. The distance between the PSISs correlated negatively with the
      iliac opening angle. The iliac opening angle was smaller in group O than in group
      C (P<0.05). The sagittal screw angle in group I was smaller than that in group C
      (P<0.01). CONCLUSIONS: Screw penetration of the outer iliac table possibly
      occurred in patients with a narrow iliac opening angle. Screw penetration of the
      inner table occurred when the screw was inserted more cranially than the sacral
      slope. Therefore, the iliac screw should be inserted approximately parallel to
      the sacral slope.

PMID- 28437346
TI  - Correlations Between Sagittal Spinal Balance and Quality of Life in Rheumatoid
      Arthritis.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To identify relationships between
      spinopelvic parameters and health-related quality of life in rheumatoid arthritis
      (RA). SUMMARY OF BACKGROUND DATA: Little data are available on relationships
      between sagittal spinopelvic parameters and health-related quality of life in RA.
      MATERIALS AND METHODS: The study and control groups comprised 120 RA patients and
      60 controls. All subjects underwent anteroposterior and lateral radiography of
      the whole spine, including hip joints, and all completed clinical questionnaires.
      The radiographic parameters examined were: sacral slope, pelvic tilt, pelvic
      incidence, thoracic kyphosis, lumbar lordosis, C7/sacrofemoral distance ratio
      (C7/SFD), and spinosacral angle (SSA). Quality of life was assessed using a
      Visual Analog Scale for back pain, the Oswestry disability index questionnaire,
      and the Scoliosis Research Society (SRS-22) questionnaire. Statistical analysis
      was performed to identify significant differences between the study and control
      groups. In addition, correlations between radiologic parameters and clinical
      questionnaires were sought. RESULTS: The patients and controls were found to be
      significantly different in terms of sacral slope, pelvic tilt, lumbar lordosis,
      thoracic kyphosis, C7/SFD, and SSA, but not for pelvic incidence (P>0.05).
      Correlation analysis revealed significant relationships between radiographic
      parameters and clinical outcomes. Multiple regression analysis was performed to
      identify predictors of clinical outcome, and the results obtained revealed that
      C7/SFD significantly predicted Visual Analog Scale score and SSA predicted
      Oswestry disability index and SRS-22 scores. CONCLUSIONS: Sagittal spinopelvic
      parameters were found to be significantly different in RA patients and normal
      controls. Correlation analysis revealed significant relationships between
      radiographic parameters and clinical outcomes. In particular, C7/SFD and SSA were
      found to be significant predictors of clinical outcomes in RA.

PMID- 28437347
TI  - Effect of Coronal Scoliotic Curvature on Sagittal Spinal Shape: Analysis of
      Parameters in Mature Adolescent Scoliosis Patients.
AB  - STUDY DESIGN: A radiographic analysis with scoliosis patients. OBJECTIVES: To
      analyze correlations between sagittal spinal alignment and coronal scoliotic
      curvature. SUMMARY OF BACKGROUND DATA: Sagittal spinal alignment and scoliosis
      may have a significant relationship, and schematic analysis is needed. METHODS:
      The study group was comprised of 163 patients with adolescent idiopathic
      scoliosis. Subjects underwent anteroposterior and lateral radiographs of the
      whole spine including hip joints. The radiographic parameters used were
      magnitude, location and direction of curve, thoracic kyphosis, thoracolumbar
      kyphosis, lumbar lordosis, sagittal balance, sacral slope, and pelvic angle.
      Subjects were classified into 4 groups according to the severity of coronal
      curvature: Cobb angle <=20 degrees, Cobb angle 21-40 degrees, Cobb angle 41-60
      degrees, and Cobb angle >60 degrees. In addition, subjects were divided into 4
      subgroups according to Roussouly's classification (types 1-4) of sagittal spinal
      shape. Schematic analysis was performed to determine the relationship between
      coronal and sagittal parameters. RESULTS: Analysis of parameters with severity of
      coronal curvature, thoracic kyphosis, and sacral slope were significantly higher
      in high-grade scoliosis (P<0.05). However, the pelvic angle was higher in low
      grade scoliosis, and sagittal balance showed a significantly higher positive
      value in low-grade scoliosis (P<0.05). In the analysis of sagittal spinal shapes,
      Roussouly groups 3 and 4 showed more severe scoliosis with higher lumbar lordosis
      and thoracic kyphosis (P<0.05). In addition, Roussouly group 1 demonstrated a
      significantly higher incidence of low-grade scoliosis, whereas groups 3 and 4 had
      a higher incidence of high-degree scoliosis by cross-relation analysis (P<0.05).
      CONCLUSIONS: A significant relationship exists between sagittal spinal shape and
      coronal curvature in scoliosis. Understanding the biplanar shapes of scoliosis
      may be helpful to the surgeons.

PMID- 28437348
TI  - The Relationship Between Cervical Degeneration and Global Spinal Alignment in
      Patients With Adult Spinal Deformity.
AB  - OBJECTIVES: To examine the relationship between cervical degeneration and spinal
      alignment by comparing patients with adult spinal deformity versus the control
      cohort. SUMMARY OF BACKGROUND DATA: The effect of degeneration on cervical
      alignment has been controversial. METHODS: Cervical and full-length spine
      radiographs of 57 patients with adult spinal deformity and 78 patients in the
      control group were reviewed. Adult spinal deformity was classified into 3 types
      based on the primary characteristics of the deformity: "Degenerative flatback"
      group, "Positive sagittal imbalance" group, and "Hyperthoracic kyphosis" group.
      Cervical degeneration was assessed using the cervical degeneration index scoring
      system. RESULTS: The "Degenerative flatback" group had significantly higher total
      cervical degeneration index score (25+/-7) than the control group (16+/-8), the
      "Positive sagittal imbalance" group (18+/-8), and the "Hyperthoracic kyphosis"
      group (12+/-7) (P<0.01). The "Degenerative flatback" group had significantly less
      cervical lordosis than the other groups. This reduced amount of cervical lordosis
      was thought to be induced by a compensatory decrease in thoracic kyphosis. In
      this group, increased cervical degeneration was significantly associated with a
      decrease in cervical lordosis. Significantly greater compensatory increase in
      cervical lordosis was noted in the "Positive sagittal imbalance" group (20+/-15
      degrees) and the "Hyperthoracic kyphosis" group (26+/-9 degrees) compared with
      the control group (11+/-12 degrees) (P<0.02). CONCLUSIONS: Flat cervical spine
      coexisted with cervical degeneration when compensatory hypothoracic kyphosis was
      induced by degenerative flatback. In other situations, cervical lordosis could
      increase as a compensatory reaction against sagittal imbalance or hyperthoracic
      kyphosis.

PMID- 28437349
TI  - A New Navigational Tool for Pedicle Screw Placement in Patients With Severe
      Scoliosis: A Pilot Study to Prove Feasibility, Accuracy, and Identify Operative
      Challenges.
AB  - STUDY DESIGN: Pilot study. OBJECTIVE: To develop and validate the feasibility and
      accuracy of a newly designed navigational spinal instrument guiding tool for
      patient-matched thoracic and lumbar pedicle screw placement in patients with
      severe scoliosis, and to identify intraoperative challenges that may be relevant.
      SUMMARY OF BACKGROUND DATA: Pedicle screw placement is challenging in severely
      rotated scoliotic spine with small diameters and asymmetrical shape of the
      pedicles and vertebrae. Patient-specific drill/positioning guides with preplanned
      trajectory have been developed as a promising solution in spinal surgery for
      precise screw insertion. METHODS: In 4 patients with severe scoliosis,
      navigational templates and models of all vertebrae to be instrumented were
      manufactured using a computed tomography (CT)-based 3-dimensional model of the
      thoracic and lumbar spine. The guides were designed differently for thoracic and
      lumbar segments according to the individual anatomy to achieve an optimal
      coupling to the surface of the patient's spine, to maximize the stability of the
      device itself, and to increase user friendliness for the complete screw
      positioning process. Intraoperative challenges and opportunities for device and
      process improvements regarding the handling of the guides during the surgery were
      recorded. Postoperatively, the intrapedicular screw positions were evaluated
      versus the preoperative plan and evaluated for cortical violation based on CT
      scans. RESULTS: A total of 76 pedicle screws were implanted (56 thoracic, 20
      lumbar). Two screws (2.6%) were assessed to be misplaced intraoperatively and
      repositioned. Eighty-four percent of the pedicle screws were completely
      intrapedicular, 96.1% within <2 mm cortical breech. CT scans did not demonstrate
      medial pedicle violation, or misplaced screw contact to neurovascular structures.
      No screw-related clinical complaints were reported postoperatively. CONCLUSIONS:
      The new custom-made positioning guide is a feasible navigational tool that
      permits a safe and accurate implantation of pedicle screws in patients with
      severe scoliosis.

PMID- 28437351
TI  - One-stage Posterior Spinal Osteotomy in Severe Spinal Deformities: A Total of 147
      Cases.
AB  - STUDY DESIGN: This is a retrospective study. OBJECTIVES: The treatment of severe
      spinal deformities is still a difficult surgical challenge. It is generally
      significant to identify the related complications performed to a consecutive
      series of patients with severe spinal deformity and managed by 1-stage posterior
      spinal osteotomy. SUMMARY OF BACKGROUND DATA: We investigated data from 147
      consecutive patients (75 males and 72 females) with severe deformity and managed
      by Smith-Petersen osteotomy, pedicle subtraction osteotomy, or vertebral column
      resection between years 2006 and 2012 with >2-year follow-up. Mean age was 21.2
      (range, 14-51 y) years at operation. MATERIALS AND METHODS: The patients
      underwent standing anteroposterior and lateral radiography before and after
      scoliosis surgery. Age, sex, diagnosis, surgical approach and centrum, all the
      related complications, treatment, and preoperative and postoperative Cobb angle
      in the coronal and sagittal planes were recorded at final follow-up. RESULTS:
      There were 17 (11.6%) cases with complications in 147 patients, including spinal
      cord-related complications in 7 cases (4.8%), superior mesenteric artery syndrome
      in 5 cases (3.4%), broken rod and unstable screw hat in 3 cases (2.0%), and
      infection in 2 cases (1.4%). Among the 17 cases, 15 cases recovered completely
      and 2 cases recovered partially. CONCLUSIONS: The total complication rate of
      severe spinal deformity after 1-stage posterior spinal osteotomy without fusion
      was about 11.6%. Except for the major complication of neurological deficit, spine
      surgeon should also pay more attention on other related complications, especially
      superior mesenteric artery syndrome. Large-scale and long-term follow-up was
      warranted to find out more subjective complication rates. LEVEL OF EVIDENCE:
      Level IV-prognostic study (see the guidelines for a complete description of
      levels of evidence).

PMID- 28437350
TI  - Biomechanical Effects of a Dynamic Topping off Instrumentation in a Long Rigid
      Pedicle Screw Construct.
AB  - STUDY DESIGN: Biomechanical ex vivo study. OBJECTIVE: To determine if topping off
      instrumentation can reduce the hypermobility in the adjacent segments when
      compared with the classic rigid spinal instrumentation. SUMMARY OF THE BACKGROUND
      DATA: Long rigid instrumentation might increase the mechanical load in the
      adjacent segments, the resulting hypermobility, and the risk for adjacent segment
      disease. Topping off instrumentation intends to reduce the hypermobility at the
      adjacent level by more evenly distributing segmental motion and, thereby,
      potentially mitigating adjacent level disease. MATERIALS AND METHODS: Eight human
      spines (Th12-L5) were divided into 2 groups. In the rigid group, a 3-segment
      metal rod instrumentation (L2-L5) was performed. The hybrid group included a 2
      segment metal rod instrumentation (L3-L5) with a dynamic topping off
      instrumentation (L2-L3). Each specimen was tested consecutively in 3 different
      configurations: native (N=8), 2-segment rod instrumentation (L3-L5, N=8), 3
      segment instrumentation (rigid: N=4, hybrid: N=4). For each configuration the
      range of motion (ROM) of the whole spine and each level was measured by a motion
      capture system during 5 cycles of extension-flexion (angle controlled to +/-5
      degrees, 0.1 Hz frequency, no preload). RESULTS: In comparison with the intact
      spine, both the rigid 3-segment instrumentation and the hybrid instrumentation
      significantly reduced the ROM in the instrumented segments (L2-L5) while
      increasing the movement in the adjacent segment L1-L2 (P=0.002, eta=0.82) and in
      Th12-L1 (P<0.001, eta=0.90). There were no ROM differences between the rigid and
      hybrid instrumentation in all segments. CONCLUSIONS: Introducing the dynamic
      topping off did not impart any significant difference in the segmental motion
      when compared with the rigid instrumentation. Therefore, the current
      biomechanical study could not show a benefit of using this specific topping off
      instrumentation to solve the problem of adjacent segment disease.

PMID- 28437352
TI  - Effect and Strategy of 1-stage Interrupted 2-level Transpedicular Wedge Osteotomy
      for Correcting Severe Kyphotic Deformities in Ankylosing Spondylitis.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To investigate the safety, outcome,
      and strategy of the 1-stage interrupted 2-level transpedicular wedge osteotomy
      for correcting the severe kyphotic deformity in ankylosing spondylitis (AS).
      SUMMARY OF BACKGROUND DATA: There has been a large series in the literature
      reporting on results of osteotomy for the correction of kyphotic deformity
      secondary to AS. However, few articles have reported, in detail, the plan,
      design, strategy, and effect of 1-stage interrupted 2-level transpedicular wedge
      osteotomy for the correction of severe kyphotic deformity in AS. MATERIALS AND
      METHODS: From May 2003 to February 2010, 24 consecutive patients, 17 males and 7
      females, suffering from AS with severe spinal kyphosis, underwent 1-stage
      interrupted 2-level transpedicular wedge osteotomy in our hospital by the
      corresponding author. Improvements in relevant parameters were recorded and
      clinical results were evaluated. RESULTS: The average operating time was 282+/-43
      minutes, and the average blood loss was 2202+/-737 mL. All the global and
      regional spinal alignments improved to relatively normal status: the global
      thoracolumbar kyphosis angle improved from 101.5+/-10.8 to 24.8+/-5.8 degrees
      (P<0.001), the thoracolumbar kyphosis improved from 37.9+/-5.1 to 0.7+/-12.8
      degrees (P<0.001), and the lumbar lordosis improved from 35.0+/-9.2 to -25.7+/
      10.9 degrees (P<0.001). Meanwhile, the chin-brow vertical angle improved from
      79.5+/-5.1 to 8.5+/-2.7 degrees (P<0.001), and the sagittal imbalance distance
      improved from 49.6+/-6.5 to 11.5+/-3.5 cm (P<0.001). All the patients could walk
      with horizontal vision and lie on their backs postoperatively, and scoliosis
      research society-22 scores improved from 1.6+/-0.2 preoperatively to 4.3+/-0.2 at
      the 2-year follow-up. The mean time of follow-up was 52+/-28 months. Fusion of
      the osteotomy was achieved in each patient and no instances of loss of correction
      or implant failure were noted. CONCLUSION: For correcting severe kyphosis in
      patients with AS, the 1-stage interrupted 2-level transpedicular wedge osteotomy
      is a safe and effective technique that significantly improves appearance and
      function.

PMID- 28437353
TI  - Evaluation of the Modern Luque Trolley Construct for the Treatment of Early-onset
      Scoliosis Using a Gliding Implant in an Immature Animal Model.
AB  - STUDY DESIGN: This was an experimental animal study. OBJECTIVE: To determine
      biological compatibility, stability, and growth potential of the Trolley Gliding
      Vehicle (TGV) used in a novel surgical technique for guided spinal growth.
      SUMMARY OF BACKGROUND DATA: Current treatments for early-onset scoliosis
      maintaining spinal growth consist of posteriorly based spinal constructs
      requiring repetitive lengthening. Such interventions have a high rate of
      complications. Using a muscle-sparing technique, a modified dual-growing rods
      construct, and new sliding spinal anchors, we aimed to test a modern Luque
      Trolley construct in an immature animal model. MATERIALS AND METHODS: Six matched
      pairs of 3-month-old lambs were randomized to an observation or a surgical group
      and were followed for 9 months. The surgical group was subjected to implantation
      of a modern Luque Trolley construct with the new TGV inserted using a minimally
      invasive transmuscular technique capturing the spine and the 2 overlapping rods
      on either side. Physical examinations and imaging were performed at routine
      intervals, with a subsequent necropsy. RESULTS: The spines of the study group
      grew 96% between the instrumented segments compared with the control group
      without evidence of implant failure. In total, 42% of the fixed anchors (pedicle
      screws) and 13.90% of the TGV were loose. All 6 animals had some heterotrophic
      bone formation tracking along the rods (<20%) mainly originating from the distal
      anchor point. We identified 19 unplanned spontaneous facet arthrodesis out of the
      132 mobile facets found between the fixed proximal and distal anchors. An
      additional 10 facets spontaneously fused proximal to the most proximal
      instrumented implants. CONCLUSIONS: Implantation of a modern Luque construct with
      TGV allows for spinal growth in a nonscoliotic animal model. Implant loosening
      was likely mechanical as no signs of reactive inflammatory reaction were found.
      Reduction of heterotrophic ossification and spontaneous facet arthrodesis remains
      a challenge in the management of immature spine.

PMID- 28437354
TI  - Complete Spondylectomy Using Orthogonal Spinal Fixation and Combined Anterior and
      Posterior Approaches for Thoracolumbar Spinal Reconstruction: Technical Nuances
      and Clinical Results.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVE: To determine the long-term
      efficacy of 2-stage total en bloc spondylectomy (TES). SUMMARY OF BACKGROUND
      DATA: TES is a well-described technique to achieve tumor-free margins, but it is
      a highly destabilizing procedure that necessitates spinal reconstruction. A 2
      stage anterior/posterior approach for tumor resection and instrumentation has
      been shown to be biomechanically superior to the single-stage approach in
      achieving rigid fixation, but few clinical studies with long-term outcomes exist.
      METHODS: A retrospective review was performed on patients undergoing a 2-stage
      TES for a spinal tumor between 1999 and 2011. Results were compared with those
      from a literature review of case series, with a minimum of 2-year follow-up,
      reporting on a single-stage posterior-only approach for TES. RESULTS: Seven
      patients were identified (average follow-up 52.7 mo). Tumor location ranged from
      T1 to L3 with the following pathologies: metastasis (n=3), hemangioma (n=1),
      leiomyosarcoma (n=1), giant cell tumor (n=1), and chordoma (n=1). There were no
      significant surgical complications. All 7 patients had intact spinal fixation.
      There were no failures of the orthogonal fixation (pedicle screws or anterior
      fixation). The average modified Rankin Scale scores improved from 2.7
      preoperatively to 0.7 at last follow-up. None of the patients in our series
      suffered local disease recurrence at last follow-up or suffered neurological
      deterioration. These results were comparable with those noted in the literature
      review of posterior-only approach, where 12% of patients experienced instrument
      failure. CONCLUSIONS: TES is a highly destabilizing procedure requiring
      reconstruction resistant to large multiplanar translational and torsional loads.
      A 2-stage approach utilizing orthogonal vertebral body screws perpendicular to
      pedicle screws is a safe and effective surgical treatment strategy. Orthogonal
      spinal fixation may lower the incidence of instrumentation failure associated
      with complete spondylectomy and appears to be comparable with a single-stage
      procedure. However, larger prospective series are necessary to assess the
      efficacy of this approach versus traditional means.

PMID- 28437355
TI  - Initial Correction Rate Can be Predictive of the Outcome of Brace Treatment in
      Patients With Adolescent Idiopathic Scoliosis.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To determine the definite cut-off
      value of initial correction rate (ICR) that could be predictive of bracing
      outcome in patients with adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND
      DATA: Earlier studies showed that braced patients with a better ICR could finally
      have a higher probability of successful outcome. However, it remains
      controversial what definitive cut-off value of ICR is required to accurately
      predict the outcome. MATERIALS AND METHODS: A cohort of 488 adolescent idiopathic
      scoliosis patients who have completed the brace treatment with a minimum of 2
      year follow-up were included in the current study. Curve progression of <=5
      degrees was used to define the success of brace treatment. The success group and
      the failure group were compared in terms of initial Risser sign, initial age,
      sex, curve pattern, initial curve magnitude, and ICR. The receiver operating
      characteristics curve was used to define the definite cut-off point of initial
      curve correction rate. A logistic regression model was created to determine the
      independent predictors of the bracing outcome. RESULTS: At the beginning of brace
      treatment, the mean age of the cohort was 13.2+/-1.5 years, and the mean curve
      magnitude was 29.5 +/- 6.6 degrees. At the final follow-up, 368 patients were
      successfully treated by bracing. Compared with the success group, the failure
      group was found to have significantly younger age, lower Risser sign, and lower
      ICR. According to the receiver operating characteristic curve, the best cut-off
      value of ICR was 10%. The logistic regression model showed that ICR was
      significantly associated with the outcome of brace treatment with an odds ratio
      of 9.61. CONCLUSIONS: Patients with low ICR, low Risser sign, and young age could
      have a remarkably high risk of bracing failure. A rate of 10% was the optimal cut
      off point for ICR, which can be used to effectively stratify braced patients.

PMID- 28437356
TI  - Scoliosis is a Risk Factor for Gastroesophageal Reflux Disease in Adult Spinal
      Deformity.
AB  - STUDY DESIGN: A prospective observational study. OBJECTIVE: To evaluate whether
      scoliosis is a risk factor for gastroesophageal reflux disease (GERD) in elderly
      patients. SUMMARY OF BACKGROUND DATA: Sagittal spinal deformities are reported to
      cause GERD, but its association with spinal deformity in the coronal plane is not
      well studied. METHODS: We examined 190 patients with spinal disorders (mean age
      70.6+/-8.6 y) who underwent standing whole-spine x-rays in the coronal and
      sagittal planes. GERD symptoms were assessed by Quest score, with a cutoff of 6
      points. The relationship between GERD symptoms and radiographic parameters was
      evaluated. Right convex coronal curves were given negative values, and left
      convex curves positive values. Degenerative scoliosis was defined when the
      thoracolumbar/lumbar Cobb angle had an absolute value >10 degrees. Risk factors
      for GERD were evaluated with univariate and multivariate logistic regression
      analyses. RESULTS: Of the patients, 126 had degenerative scoliosis at the
      thoracolumbar/lumbar spine (42 with right and 84 with left convex curve), and 59
      had GERD. Multivariate logistic regression analysis revealed that the lumbar Cobb
      angle was significantly associated with GERD (P<0.05, odds ratio=1.021). When
      patients were categorized by Cobb angle of the lumbar curve (<-30 degrees, large
      right convex curve; -30 to +30 degrees, small curve; or >+30 degrees, large left
      convex curve), a large left convex curve was strongly associated with GERD
      (P<0.05, odds ratio=10.925). CONCLUSIONS: Left thoracolumbar/lumbar curve was a
      significant risk factor for GERD, and risk increased with a curve >30 degrees.
      Organ disorders such as GERD should be considered when treating elderly patients
      with degenerative scoliosis.

PMID- 28437357
TI  - The Effect of Concomitant Rib Deformity in Congenital Scoliosis on Spinal Curve
      Correction After Segmental Pedicle Screw Instrumentation.
AB  - STUDY DESIGN: A single-center, prospective study. OBJECTIVE: To investigate the
      effect of rib anomaly on surgical curve correction outcome in congenital
      scoliosis. SUMMARY OF BACKGROUND DATA: The presence of rib anomalies may
      complicate surgical correction of congenital scoliosis. The outcome of surgical
      correction, however, has not been documented in scoliotic patients with and
      without rib deformity. METHODS: Percent Cobb angle decrease (CAD) after operation
      was calculated in 94 patients with congenital scoliosis. Posterior segmental
      pedicle screw instrumentation (posterior approach) with or without previous
      anterior spinal release and fusion (anterior approach) was the method of
      correction. The impact of vertebral anomaly and rib deformity on CAD was
      examined. RESULTS: Although the type of vertebral anomaly had no significant
      effect on the mean CAD, it was significantly lower in 56 patients with rib
      deformity compared with that in the remaining patients without rib deformity
      (35.14%+/-15.83% vs. 51.54%+/-17.82%, P<0.001); particularly in those with
      complex, unilateral rib abnormalities, and in those with same-level vertebral and
      rib deformities. Patients' sex and age at the time of operation, rib number
      abnormality, and the type of operation (ie, posterior-only approach vs. anterior
      and posterior approach) did not contribute significantly to Cobb angle change
      after operation. CONCLUSIONS: Concomitant rib deformities, particularly of
      complex and unilateral types, significantly compromise operative curve correction
      outcome in congenital scoliosis.

PMID- 28437358
TI  - Integrated Multidimensional Maturity Assessments Predicting the High-risk
      Occurrence of Peak Angle Velocity During Puberty in Progressive Female Idiopathic
      Scoliosis.
AB  - STUDY DESIGN: A consecutive and prospective longitudinal study. OBJECTIVE: To
      propose an integrated multidimensional maturity assessment that was designated as
      forming a reliable system precisely predicting the high-risk occurrence of peak
      angle velocity (PAV) in a group of progressive braced female idiopathic scoliosis
      (IS). SUMMARY OF BACKGROUND DATA: Scoliosis deterioration is believed to keep
      pace with the evolution of skeletal maturity during puberty. There is, however, a
      paucity of data in the literature regarding which unidimensional or
      multidimensional maturity assessment was most informational, and could be
      employed to predict the likelihood of significant curve progression. MATERIALS
      AND METHODS: In this prospective study, braced IS girls with open triradiate
      cartilage were recruited and followed up at 6-month regular intervals. At each
      visit, the following data were collected: chronologic age, stage of menses,
      standing height, Cobb angle of the main curve, spine length, status of triradiate
      cartilage, Risser sign, and digital skeletal age (DSA) scores. The height
      velocity (HV) and spine length velocity (SLV), as well as the angle velocity (AV)
      of each visit were calculated. Finally, those with main curve progression of >=5
      degrees during brace treatment and with a minimum of 2-year follow-up covering
      the closure of the triradiate cartilage were recruited in this analysis, and
      their PAV was defined as the peak of AV curves during the whole follow-up period
      in puberty. Logistic regression analysis was used to evaluate the contribution of
      each measurement to the risk of PAV onset. RESULTS: Thirty-six IS girls were
      finally recruited in the study, with an average age of 10.8 years at initial
      visit and 11.8 years at PAV. The average DSA score, spine length, standing
      height, and Cobb angle of main curve at PAV were 479.5, 326.7 mm, 150.8 cm, and
      26.5 degrees, respectively. The average HV, AV, and SLV at PAV were 8.3 cm, 7.8
      degrees, and 28.2 mm/y, respectively. The PAV occurred with Risser 0, 1, and 2 in
      80.6%, 11.1%, and 8.3% of the IS girls and closed triradiate cartilages were
      found at PAV in all the girls. The logistic regression model revealed that the
      following variables contributed significantly to high-risk occurrence of PAV:
      chronologic age between 11 and 13 years [odds ratio (OR)=3.961; 95% confidence
      interval (CI), 1.023-15.342], Risser 0 (OR=14.261; 95% CI, 1.167-65.528), closed
      triradiate cartilage (OR=6.590; 95% CI, 1.612-26.943), DSA scores between 400 and
      500 (OR=6.042; 95% CI, 1.282-28.482), HV>6 cm/y (OR=5.711; 95% CI, 1.105-29.526),
      Cobb angle of main curve >30 degrees (OR=5.492; 95% CI, 1.151-26.207) and SLV>20
      mm/y (OR=5.973; 95% CI, 1.546-23.071). CONCLUSIONS: Integrated multidimensional
      maturity assessments, defined as chronologic age between 11 and 13 years,
      modified Risser 0, DSA scores between 400 and 500, HV>6 cm/y, and SLV>20 mm/y,
      combined with preexisting scoliotic curve >30 degrees, were prone to increase the
      risk of entering the rapid curve acceleration phase in progressive IS girls.

PMID- 28437359
TI  - What's in a Med Check? Unpacking the "Psychopharmacology" Encounter.

PMID- 28437360
TI  - DNA Hydroxymethylation by Ten-eleven Translocation Methylcytosine Dioxygenase 1
      and 3 Regulates Nociceptive Sensitization in a Chronic Inflammatory Pain Model.
AB  - BACKGROUND: Ten-eleven translocation methylcytosine dioxygenase converts 5
      methylcytosine in DNA to 5-hydroxymethylcytosine, which plays an important role
      in gene transcription. Although 5-hydroxymethylcytosine is enriched in mammalian
      neurons, its regulatory function in nociceptive information processing is
      unknown. METHODS: The global levels of 5-hydroxymethylcytosine and ten-eleven
      translocation methylcytosine dioxygenase were measured in spinal cords in mice
      treated with complete Freund's adjuvant. Immunoblotting, immunohistochemistry,
      and behavioral tests were used to explore the downstream ten-eleven translocation
      methylcytosine dioxygenase-dependent signaling pathway. RESULTS: Complete
      Freund's adjuvant-induced nociception increased the mean levels (+/- SD) of
      spinal 5-hydroxymethylcytosine (178 +/- 34 vs. 100 +/- 21; P = 0.0019), ten
      eleven translocation methylcytosine dioxygenase-1 (0.52 +/- 0.11 vs. 0.36 +/-
      0.064; P = 0.0088), and ten-eleven translocation methylcytosine dioxygenase-3
      (0.61 +/- 0.13 vs. 0.39 +/- 0.08; P = 0.0083) compared with levels in control
      mice (n = 6/group). The knockdown of ten-eleven translocation methylcytosine
      dioxygenase-1 or ten-eleven translocation methylcytosine dioxygenase-3 alleviated
      thermal hyperalgesia and mechanical allodynia, whereas overexpression
      cytosinethem in naive mice (n = 6/group). Down-regulation of spinal ten-eleven
      translocation methylcytosine dioxygenase-1 and ten-eleven translocation
      methylcytosine dioxygenase-3 also reversed the increases in Fos expression (123
      +/- 26 vs. 294 +/- 6; P = 0.0031; and 140 +/- 21 vs. 294 +/- 60; P = 0.0043,
      respectively; n = 6/group), 5-hydroxymethylcytosine levels in the Stat3 promoter
      (75 +/- 16.1 vs. 156 +/- 28.9; P = 0.0043; and 91 +/- 19.1 vs. 156 +/- 28.9; P =
      0.0066, respectively; n = 5/group), and consequent Stat3 expression (93 +/- 19.6
      vs. 137 +/- 27.5; P = 0.035; and 72 +/- 15.2 vs. 137 +/- 27.5; P = 0.0028,
      respectively; n = 5/group) in complete Freund's adjuvant-treated mice.
      CONCLUSIONS: This study reveals a novel epigenetic mechanism for ten-eleven
      translocation methylcytosine dioxygenase-1 and ten-eleven translocation
      methylcytosine dioxygenase-3 in the modulation of spinal nociceptive information
      via targeting of Stat3.

PMID- 28437361
TI  - Cochlear Implantation: Vast Unmet Need to Address Deafness Globally.

PMID- 28437362
TI  - Sonotubometric Assessment for Severity of Patulous Eustachian Tube.
AB  - OBJECTIVE: To investigate the relationship between the morphological patency of
      the eustachian tube (ET) and sound transmission via the ET. STUDY DESIGN:
      Retrospective chart review and model experiment. SETTING: Tertiary referral
      center. SUBJECTS: A total of 56 ears of 28 patients (9 men and 19 women, aged
      from 12 to 82 yr, mean 40.4 +/- 21.5 yr) who underwent sonotubometric measurement
      using postural change as well as computed tomography (CT) of the ET in the
      sitting position, including 26 ears with definite patulous ET, 9 ears with
      possible patulous ET, and 21 ears without patulous ET. METHOD: Commercial
      equipment for sonotubometry (JK-05A; RION Co., Ltd., Kokubunji, Tokyo, Japan) was
      used in the following two investigations. Retrospective survey: sound patency of
      7 kHz band noise via the ET was assessed by comparison of acoustic transfer
      function via the ET in the sitting and forward-bending positions. Sound patency
      via the ET was compared with morphological patency of the ET (cross-sectional
      area in the narrowest portion) assessed by three-dimensional CT of the ET in the
      sitting position. Model experiment: effect of the ET caliber on the acoustic
      transfer function was examined using a simple model constructed with two
      truncated syringes with silicone barrels and a narrow connecting tube. RESULTS:
      Sound patency assessed by sonotubometry was well correlated with the cross
      sectional area at the narrowest portion of the ET in the sitting position (r =
      0.786, p < 0.001). Correlation between the sound patency via the narrow tube and
      the caliber of the tube was also confirmed by the model experiment. CONCLUSIONS:
      Sound patency assessed by sonotubometry using 7 kHz band noise could be useful to
      predict the morphological severity of patulous ET.

PMID- 28437363
TI  - Intratympanic Dexamethasone in the Treatment of Meniere's Disease: A Comparison
      of Two Techniques.
AB  - OBJECTIVE: To assess the efficacy and safety of two different intratympanic
      dexamethasone (IT Dex) injection protocols for intractable unilateral Meniere's
      disease. STUDY DESIGN: Prospective case series. SETTING: Tertiary neurotology
      clinic. PATIENTS: One hundred six consecutive adult patients with definite
      unilateral Meniere's disease who had failed medical management were studied for
      an average of 1,061 days. None had previous oral steroid, IT steroid, or ablative
      treatment. INTERVENTIONS: Two different IT Dex regimes, either a single injection
      or a series of four injections, that were subsequently repeated as indicated.
      MAIN OUTCOME MEASURE: Requirement for subsequent ablative therapy in the form of
      intratympanic gentamicin, vestibular nerve section, or labyrinthectomy. Hearing
      outcomes were measured using pure-tone average of 0.5, 1, 2, and 3 kHz on
      standard audiometry. RESULTS: The number of intratympanic dexamethasone
      injections per patient ranged from 1 to 29 (median = 4). Using the Kaplan-Meier
      method, predicted survival (patients not requiring ablative therapy) at 2 and 4
      years after initial treatment was 83.9 and 79.3%, respectively. The injection
      series protocol ultimately yielded 5% better survival than the single injection
      protocol, but this was not statistically significant. Injections did not protect
      against hearing loss, and the most recent pure-tone averages declined compared
      with pretreatment values by an average of 8.27 dB (p < 0.05). The treatments did
      not result in any acute hearing losses, permanent tympanic membrane perforations,
      or other significant adverse events. CONCLUSION: Intratympanic dexamethasone
      injections were successful in controlling vertigo insofar as they were able to
      obviate ablative therapy in the majority of Meniere's disease patients in this
      study. The injection series protocol may have been more beneficial compared with
      the single injection, although the difference between the two protocols was
      nonsignificant. Hearing mildly declined over the treatment course, which likely
      represents natural disease progression. The lack of adverse events suggests that
      IT Dex may be a nonablative option for patients with bilateral disease or only
      hearing/vestibular ears.

PMID- 28437364
TI  - A Technique for the Management of Concomitant Scaphotrapezoid Arthritis in
      Patients With Thumb Metacarpotrapezial Arthritis: Interposition Arthroplasty With
      a Capitate Suture Anchor.
AB  - Scaphotrapezoid (ST) arthritis is a common source of pain and disability that
      typically presents with concomitant basilar thumb arthritis. ST arthritis is
      often under recognized and under diagnosed as a source of continued pain after
      successful basilar thumb arthroplasty. Untreated, symptomatic ST arthritis can
      cause failure of an otherwise successfully executed thumb carpometacarpal
      arthroplasty due to persistent pain, which is frustrating to the patient and
      surgeon. Although multiple surgical treatment options have been described for
      basilar thumb carpometacarpal joint arthritis, there is no gold standard for the
      treatment of ST arthritis. We describe a surgical technique with a minimal
      trapezoid excision and interpositional arthroplasty using an acellular allograft
      secured with a suture anchor in the capitate.

PMID- 28437365
TI  - A Method to Account for Variation in Congenital Heart Surgery Length of Stay.
AB  - OBJECTIVES: We sought to develop a risk-adjustment methodology for length of stay
      in congenital heart surgery, as none exist. DESIGN: Prospective cohort analysis
      combined with previously obtained retrospective cohort analysis of a Department
      of Cardiovascular Surgery clinical database. PATIENTS: Patients discharged from
      Boston Children's Hospital between October 1, 2006, and May 31, 2014, that
      underwent a congenital heart surgery procedure(s) linked to one of 103 surgical
      procedure types. MEASUREMENTS AND MAIN RESULTS: Six thousand two hundred nine
      discharges during the reporting period at Boston Children's Hospital comprised
      the cohort. Seven Surgical Length Categories were developed to group surgical
      procedure types. A multivariable model for outcome length of stay was built using
      a derivation cohort consisting of a 75% random sample, starting with Surgical
      Length Categories and considering additional a priori factors. Postoperative
      factors were then added to improve predictive performance. The remaining 25% of
      the cohort was used to validate the multivariable models. The coefficient of
      determination (R) was used to estimate the variability in length of stay
      explained by each factor. The Surgical Length Categories yielded an R of 42%.
      Model performance increased when the a priori factors preoperative status,
      noncardiac abnormality, genetic anomaly, preoperative catheterization during
      episode of care, weight less than 3 kg, and preoperative vasoactive support
      medication were introduced to the model (R = 60.8%). Model performance further
      improved when postoperative ventilation greater than 7 days, operating room time,
      postoperative catheterization during episode of care, postoperative reintubation,
      number of postoperative vasoactive support medications, postoperative ICU
      infection, and greater than or equal to one secondary surgical procedure were
      added (R = 76.7%). The validation cohort yielded an R of 76.5%. CONCLUSIONS: We
      developed a statistically valid procedure-based categorical variable and
      multivariable model for length of stay of congenital heart surgeries. The
      Surgical Length Categories and important a priori and postoperative factors may
      be used to pursue a predictive tool for length of stay to inform scheduling and
      bed management practices.

PMID- 28437366
TI  - The Impact of Residual Subgingival Cement on Biological Complications Around
      Dental Implants: A Systematic Review.
AB  - OBJECTIVES: To perform a systematic review on the impact of residual subgingival
      cement on peri-implant diseases and crestal bone loss. MATERIAL AND METHODS:
      MEDLINE, SCOPUS, ISI Web of Knowledge and Cochrane Central Register of Controlled
      Trials (CENTRAL) databases were used to identify articles published without time
      limits. RESULTS: A total of 6 articles were selected for a total of 389 patients
      (687 implants). The studies were heterogeneous and had a moderate-to-high risk of
      bias, but met the inclusion criteria. Four of 6 studies were published by the
      same research group and assessed similar populations over time. A positive
      relationship between residual cement and peri-implant inflammation was observed.
      Data on peri-implant probing depths and crestal bone loss were reported in 1
      study. CONCLUSION: Residual subgingival cement seems to be strongly associated
      with peri-implant mucositis which is a risk factor for increased probing depths
      crestal bone loss and peri-implantitis. Zinc oxide eugenol cements should be
      preferred to resin cements especially in patients with a history of
      periodontitis.

PMID- 28437367
TI  - "Effective" Requesting: A Scoping Review of the Literature on Asking Families to
      Consent to Organ and Tissue Donation.
AB  - BACKGROUND: Families are often asked to consent to the donation of their deceased
      relative's organs or tissues. These end-of-life conversations are important
      because they affect consent rates as well as the psychological impact of the
      decision for families. This scoping review of the literature on requesting family
      consent was prepared to support of the development of leading practice
      recommendations for end-of-life conversations with families of potential donors.
      A scoping review maps research activity in a field across a range of commentary
      and empirical study designs but does not attempt meta-synthesis of empirical data
      or quality assessment. METHODS: We performed a scoping review of the peer
      reviewed literature from January 2000 to February 2015 on the questions of what
      constitutes an "effective" request and the factors that affect consent rates and
      family satisfaction with their decision and the process. This review includes a
      final set of 168 articles addressing (a) whether, when, and how to ask families
      for consent to donation or (b) characteristics of families or decedents that
      affect families' decisions or family satisfaction with their decisions. RESULTS:
      Six main themes were identified: (1) the objectives of requesting and encouraging
      family consent to donation, (2) the effect of the donation decision on family
      well-being, (3) the process of requesting family consent, (4) the impact of the
      quality of the care for the deceased and for the family, (5) the content and
      manner of the request for family consent, and (6) the characteristics of the
      family and deceased that affect the request for family consent. CONCLUSION: This
      scoping review found that there is a large literature on how to modify the
      process and manner of the request to increase family consent rates. Another
      important line of inquiry focuses on the psychological impact of the decision on
      the family. Although a scoping review does not attempt to synthesize results or
      draw evidence-based conclusions, the literature generally supports the intuitive
      expectations that compassionate and respectful care for the deceased and family,
      listening for and addressing family concerns, and an attitude to donation that is
      positive (but not solely procurement-focused) and is best for both consent rates
      and family well-being. Although the presumption is often that the primary
      objective of asking for family consent is to secure consent and donation, some
      ethical commentary on requesting consent emphasizes that this objective must be
      balanced with the parallel obligation to protect the psychological well-being of
      families. This places some constraints on the approaches used in family consent
      discussions.

PMID- 28437368
TI  - End-of-Life Conversations With Families of Potential Donors: Leading Practices in
      Offering the Opportunity for Organ Donation.

PMID- 28437369
TI  - Ethical Challenges and the Donation Physician Specialist: A Scoping Review.
AB  - Deceased donation medicine involves unique ethical challenges. Physicians who are
      focused on deceased donation medicine as part of their practice can expect to
      encounter these challenges. The goal of this review is to identify and describe
      these challenges, highlight existing guidelines and policy regarding the
      management of these challenges and to describe how the donation physician role
      might promote ethical practice in deceased donation medicine. Themes of
      discussion include: communication with families, interprofessional conflict,
      donation physician personal characteristics, donation clinical processes, health
      resource allocation, research and education, and remuneration. The information
      presented in this review can be used to inform development of recommendations and
      guidelines for the management of ethical challenges encountered by donation
      physicians.

PMID- 28437370
TI  - Ethics Guide Recommendations for Organ-Donation-Focused Physicians: Endorsed by
      the Canadian Medical Association.
AB  - Donation physicians are specialists with expertise in organ and tissue donation
      and have been recognized internationally as a key contributor to improving organ
      and tissue donation services. Subsequent to a 2011 Canadian Critical Care Society
      Canadian Blood Services consultation, the donation physician role has been
      gradually implemented in Canada. These professionals are generally intensive care
      unit physicians with an enhanced focus and expertise in organ/tissue donation.
      They must manage the dual obligation of caring for dying patients and their
      families while providing and/or improving organ donation services. In
      anticipation of actual, potential or perceived ethical challenges with the role,
      Canadian Blood Services in partnership with the Canadian Medical Association
      organized the development of an evidence-informed consensus process of donation
      experts and bioethicists to produce an ethics guide. This guide includes
      overarching principles and benefits of the DP role, and recommendations in regard
      to communication with families, role disclosure, consent discussions,
      interprofessional conflicts, conscientious objection, death determination,
      donation specific clinical practices in neurological determination of death and
      donation after circulatory death, end-of-life care, performance metrics,
      resources and remuneration. Although this report is intended to inform donation
      physician practices, it is recognized that the recommendations may have
      applicability to other professionals (eg, physicians in intensive care, emergency
      medicine, neurology, neurosurgery, pulmonology) who may also participate in the
      end-of-life care of potential donors in various clinical settings. It is hoped
      that this guidance will assist practitioners and their sponsoring organizations
      in preserving their duty of care, protecting the interests of dying patients, and
      fulfilling best practices for organ and tissue donation.

PMID- 28437372
TI  - Heart Rate Modification of Cardiac Output Following Cardiac Surgery: The
      Importance of Cardiac Time Intervals.
AB  - OBJECTIVES: Inadequate cardiac output is associated with a poor outcome following
      cardiac surgery and is generally modified by the use of positive inotropic
      agents, volume resuscitation, and pacing. Echocardiography-guided pacemaker
      optimization is used in the outpatient setting, using different variables
      including total isovolumic time and the Tei index. We sought to determine the
      acute impact of heart rate on cardiac electromechanics, cardiac output, and
      stroke volume in the perioperative setting. DESIGN: Observational study. SETTING:
      Cardiothoracic adult intensive care department. PATIENTS: Twenty-four sequential
      patients admitted after cardiac surgery. INTERVENTIONS: Patients with pacemaker
      set by the treating anesthesiologist using hemodynamic parameters in theatre,
      within 4 hours of returning to intensive care, they were reassessed using
      transthoracic echocardiography. A comprehensive baseline echocardiographic study
      was performed at the clinician set RR interval and at heart rates from 70 to 110
      beats/min, in increments of 10 beats/min. Pearson correlation coefficients were
      used to assess relationships between the measurements. MEASUREMENTS AND MAIN
      RESULTS: Cardiac output and cardiac index were increased significantly in 79%
      patients using echocardiography-guided pacemaker optimization (2.21 L/min [+/-
      0.97] and 1.2 L/min/m [+/- 0.52]). The echocardiography-driven cardiac output
      optimization protocol led to a significant reduction of total isovolumic time
      with concurrent increase of cardiac output and cardiac index in the overall
      population (p < 0.001). There was no consistent correlation between changes in RR
      interval and stroke volume, cardiac output, or cardiac index in the overall
      population. A strong negative correlation was found between the left ventricular
      total isovolumic time and stroke volume, cardiac output, and cardiac index in all
      groups. CONCLUSION: Echocardiography-guided heart rate optimization results in a
      significant increase in cardiac output when compared with clinically derived
      pacing settings in the postoperative period. The optimal heart rate should be
      individualized for each patient, and total isovolumic time is the
      echocardiographic index with the highest sensitivity to determine the optimal
      hemodynamic profile.

PMID- 28437373
TI  - Resuscitation With Balanced Fluids Is Associated With Improved Survival in
      Pediatric Severe Sepsis.
AB  - OBJECTIVE: To evaluate outcomes in patients receiving balanced fluids for
      resuscitation in pediatric severe sepsis. DESIGN: Observational cohort review of
      prospectively collected data from a large administrative database. SETTING: PICUs
      from 43 children's hospitals. PATIENTS: PICU patients diagnosed with severe
      sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed data from
      the Pediatric Health Information System database from 2004 to 2012. Children with
      pediatric severe sepsis receiving balanced fluids for resuscitation in the first
      24 and 72 hours of treatment were compared to those receiving unbalanced fluids.
      Thirty-six thousand nine hundred eight patients met entry criteria for analysis.
      Two thousand three hundred ninety-eight patients received exclusively balanced
      fluids at 24 hours and 1,641 at 72 hours. After propensity matching, the 72-hour
      balanced fluids group had lower mortality (12.5% vs 15.9%; p = 0.007; odds ratio,
      0.76; 95% CI, 0.62-0.93), lower prevalence of acute kidney injury (16.0% vs
      19.2%; p = 0.028; odds ratio, 0.82; 95% CI, 0.68-0.98), and fewer vasoactive
      infusion days (3.0 vs 3.3 d; p < 0.001) when compared with the unbalanced fluids
      group. CONCLUSIONS: In this retrospective analysis carried out by propensity
      matching, exclusive use of balanced fluids in pediatric severe sepsis patients
      for the first 72 hours of resuscitation was associated with improved survival,
      decreased prevalence of acute kidney injury, and shorter duration of vasoactive
      infusions when compared with exclusive use of unbalanced fluids.

PMID- 28437374
TI  - ICU Patients Requiring Renal Replacement Therapy Initiation: Fewer Survivors and
      More Dialysis Dependents From 80 Years Old.
AB  - OBJECTIVES: To assess the role of advanced age on survival and dialysis
      dependency after initiation of renal replacement therapy for acute kidney injury.
      DESIGN: Retrospective pooled analysis of prospectively collected data. SETTING:
      ICUs of two teaching hospitals in Paris area, France. SUBJECTS: One thousand five
      hundred thirty adult patients who required renal replacement therapy initiation
      in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Survival and post
      acute kidney injury chronic dialysis dependency were assessed at hospital
      discharge according to the quintile (Q) of age. The oldest quintile included 289
      patients 80 years old and over. Seventy-three percent of included patients had
      respiratory and hemodynamic supports at renal replacement therapy initiation,
      similarly distributed across quintiles. Mortality increased with age strata from
      63% in Q1 (<= 52 yr) to 76% in Q5 (>= 80 yr) (p < 0.001). After adjustment, age
      did not increase the risk of death up to 80 years. The oldest patients (>= 80 yr)
      had a significant higher risk of dying (adjusted odds ratio, 2.59; 95% CI, 1.66
      4.03). Dialysis dependency was more frequent among survivors 80 years old or
      older (30% vs 14%; p = 0.001). Age 80 years old or older was an independent risk
      for dialysis dependency only for patients with prior advanced chronic kidney
      disease (p = 0.04). Baseline estimated glomerular filtration rate was the only
      one predictor of dialysis dependency identified. CONCLUSIONS: Patients with
      advanced age represent a substantial subgroup of patients requiring renal
      replacement therapy in the ICU. From 80 years, age should be considered as an
      additional risk of dying over the severity of organ failures. Patients 80 years
      old or older are likely to recover sufficient renal function allowing renal
      replacement therapy discontinuation when baseline estimated glomerular filtration
      rate is above 44 mL/min/1.73 m. At 3 months, only 6% were living at home,
      dialysis independent.

PMID- 28437375
TI  - Both Positive and Negative Fluid Balance May Be Associated With Reduced Long-Term
      Survival in the Critically Ill.
AB  - OBJECTIVES: Among critically ill patients with acute kidney injury, exposure to
      positive fluid balance, compared with negative fluid balance, has been associated
      with mortality and impaired renal recovery. However, it is unclear whether
      positive and negative fluid balances are associated with poor outcome compared to
      patients with even fluid balance (euvolemia). In this study, we examined the
      association between exposure to positive or negative fluid balance, compared with
      even fluid balance, on 1-year mortality and renal recovery. DESIGN: Retrospective
      cohort study. SETTING: Eight medical-surgical ICUs at the University of
      Pittsburgh Medical Center, Pittsburgh, PA. PATIENTS: Critically ill patients
      admitted between July 2000 and October 2008. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Among 18,084 patients, fluid balance was categorized as
      negative (< 0%), even (0% to < 5%), or positive (>= 5%). Following propensity
      matching, positive fluid balance, compared with even or negative fluid balance,
      was associated with increased mortality (30.3% vs 21.1% vs 22%, respectively; p <
      0.001). Using Gray's model, negative fluid balance, compared with even fluid
      balance, was associated with lower short-term mortality (adjusted hazard ratio
      range, 0.81; 95% CI, 0.68-0.96) but higher long-term mortality (adjusted hazard
      ratio range, 1.16-1.22; p = 0.004). Conversely, positive fluid balance was
      associated with higher mortality throughout 1-year (adjusted hazard ratio range,
      1.30-1.92; p < 0.001), which was attenuated in those who received renal
      replacement therapy (positive fluid balance * renal replacement therapy
      interaction (adjusted hazard ratio range, 0.43-0.89; p < 0.001). Of patients
      receiving renal replacement therapy, neither positive (adjusted odds ratio, 0.98;
      95% CI, 0.68-1.4) nor negative (adjusted odds ratio, 0.81; 95% CI, 0.43-1.55)
      fluid balance was associated with renal recovery. CONCLUSIONS: Among critically
      ill patients, exposure to positive or negative fluid balance, compared with even
      fluid balance, was associated with higher 1-year mortality. This mortality risk
      associated with positive fluid balance, however, was attenuated by use of renal
      replacement therapy. We found no association between fluid balance and renal
      recovery.

PMID- 28437376
TI  - Organizational Issues, Structure, and Processes of Care in 257 ICUs in Latin
      America: A Study From the Latin America Intensive Care Network.
AB  - OBJECTIVE: Latin America bears an important burden of critical care disease, yet
      the information about it is scarce. Our objective was to describe structure,
      organization, processes of care, and research activities in Latin-American ICUs.
      DESIGN: Web-based survey submitted to ICU directors. SETTINGS: ICUs located in
      nine Latin-American countries. SUBJECTS: Individual ICUs. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-seven of 498 (52%) of submitted
      surveys responded: 51% from Brazil, 17% Chile, 13% Argentina, 6% Ecuador, 5%
      Uruguay, 3% Colombia, and 5% between Mexico, Peru, and Paraguay. Seventy-nine
      percent of participating hospitals had less than 500 beds; most were public (59%)
      and academic (66%). ICUs were mainly medical-surgical (75%); number of beds was
      evenly distributed in the entire cohort; 77% had 24/7 intensivists; 46% had a
      physician-to-patient ratio between 1:4 and 7; and 69% had a nurse-to-patient
      ratio of 1 >= 2.1. The 24/7 presence of other specialists was deficient.
      Protocols in use averaged 9 +/- 3. Brazil (vs the rest) had larger hospitals and
      ICUs and more quality, surveillance, and prevention committees, but fewer 24/7
      intensivists and poorer nurse-to-patient ratio. Although standard monitoring,
      laboratory, and imaging practices were almost universal, more complex
      measurements and treatments and portable equipment were scarce after standard
      working hours, and in public hospitals. Mortality was 17.8%, without differences
      between countries. CONCLUSIONS: This multinational study shows major concerns in
      the delivery of critical care across Latin America, particularly in human
      resources. Technology was suboptimal, especially in public hospitals. A 24/7
      availability of supporting specialists and of key procedures was inadequate.
      Mortality was high in comparison to high-income countries.

PMID- 28437377
TI  - MicroRNA-21 Is Required for Local and Remote Ischemic Preconditioning in Multiple
      Organ Protection Against Sepsis.
AB  - OBJECTIVE: Sepsis, triggered by microbial infection, is a common and life
      threatening systemic illness, often leads to impaired function of vital organs.
      Ischemic preconditioning induced by transient brief episodes of ischemia is a
      powerful innate mechanism of organ protection. We have reported that a 15-minute
      renal ischemic preconditioning substantially attenuated subsequent renal ischemia
      reperfusion injury. Here, we investigate whether a brief ischemia and reperfusion
      in kidney can provide protection at local and remote sites against sepsis-induced
      organ injury, and whether this protection is microRNA-21 dependent. DESIGN:
      Laboratory study. SETTING: University laboratory. SUBJECTS: Mouse renal tubular
      epithelial cells, C57BL/6 J wildtype (Animal Center of Fudan University,
      Shanghai, China) and microRNA-21-/- mice (B6.129-Mir21atm1Smoc, Shanghai Biomodel
      Organism Science & Technology Development Co. Shanghai, China). INTERVENTIONS:
      Mouse renal tubular epithelial cells were treated with hypoxia (2% oxygen). Renal
      ischemic preconditioning was induced by bilateral renal pedicle clamping for 15
      minutes, and sepsis was induced by a single intraperitoneal injection of
      lipopolysaccharide at a dose of 20 mg/kg or cecal ligation and puncture in mice.
      MEASUREMENTS AND MAIN RESULTS: Mice treated with renal ischemic preconditioning
      were protected from endotoxemia or polymicrobial sepsis-induced multiple organ
      injury, including kidneys, heart, liver, and lungs. Renal ischemic
      preconditioning induced activation of hypoxia-inducible factor-1alpha in kidneys,
      which up-regulated microRNA-21 at transcriptional level, subsequently, leading to
      increased expression of microRNA-21 in serum exosomes and remote organs,
      resulting in decreased apoptosis and reduced proinflammatory cytokines production
      in these organs. In vivo knockdown of microRNA-21 or genetic deletion of microRNA
      21 abrogated the organoprotective effects conferred by renal ischemic
      preconditioning. Mechanistically, we discovered that knockdown of microRNA-21
      increased programmed cell death protein 4 expression and nuclear factor-kappa B
      activity, decreased expression of anti-apoptotic B-cell lymphoma-2. CONCLUSION:
      MicroRNA-21 is required for local and remote ischemic preconditioning in multiple
      organ protection against sepsis, and up-regulation of miR-21 may be a potential
      therapy for sepsis.

PMID- 28437378
TI  - Risk Factors for Pediatric Extubation Failure: The Importance of Respiratory
      Muscle Strength.
AB  - OBJECTIVE: Respiratory muscle weakness frequently develops during mechanical
      ventilation, although in children there are limited data about its prevalence and
      whether it is associated with extubation outcomes. We sought to identify risk
      factors for pediatric extubation failure, with specific attention to respiratory
      muscle strength. DESIGN: Secondary analysis of prospectively collected data.
      SETTING: Tertiary care PICU. PATIENTS: Four hundred nine mechanically ventilated
      children. INTERVENTIONS: Respiratory measurements using esophageal manometry and
      respiratory inductance plethysmography were made preextubation during airway
      occlusion and on continuous positive airway pressure of 5 and pressure support of
      10 above positive end-expiratory pressure 5 cm H2O, as well as 5 and 60 minutes
      postextubation. MEASUREMENTS AND MAIN RESULTS: Thirty-four patients (8.3%) were
      reintubated within 48 hours of extubation. Reintubation risk factors included
      lower maximum airway pressure during airway occlusion (aPiMax) preextubation,
      longer length of ventilation, postextubation upper airway obstruction, high
      respiratory effort postextubation (pressure rate product, pressure time product,
      tension time index), and high postextubation phase angle. Nearly 35% of children
      had diminished respiratory muscle strength (aPiMax <= 30 cm H2O) at the time of
      extubation, and were nearly three times more likely to be reintubated than those
      with preserved strength (aPiMax > 30 cm H2O; 14% vs 5.5%; p = 0.006).
      Reintubation rates exceeded 20% when children with low aPiMax had moderately
      elevated effort after extubation (pressure rate product > 500), whereas children
      with preserved aPiMax had reintubation rates greater than 20% only when
      postextubation effort was very high (pressure rate product > 1,000). When
      children developed postextubation upper airway obstruction, reintubation rates
      were 47.4% for those with low aPiMax compared to 15.4% for those with preserved
      aPiMax (p = 0.02). Multivariable risk factors for reintubation included acute
      neurologic disease, lower aPiMax, postextubation upper airway obstruction, higher
      preextubation positive end-expiratory pressure, higher postextubation pressure
      rate product, and lower height. CONCLUSIONS: Neuromuscular weakness at the time
      of extubation was common in children and was independently associated with
      reintubation, particularly when postextubation effort was high.

PMID- 28437379
TI  - Associations of Lifetime Trauma and Chronic Stress With C-reactive Protein in
      Adults Ages 50 Years and Older: Examining the Moderating Role of Perceived
      Control.
AB  - OBJECTIVE: The aim of the study was to investigate whether high perceived control
      mitigates systemic inflammatory risk associated with traumatic and chronic stress
      exposures in older adults. METHODS: A sample of community-dwelling adults ages 50
      years and older (N = 4779) was drawn from the Health and Retirement Study.
      Structural equation models tested interactions of lifetime trauma and chronic
      stress with mastery and perceived constraints predicting baseline levels and 4
      year change in C-reactive protein (CRP). RESULTS: There were significant
      interactions of lifetime trauma (beta = -.058, p = .012) and chronic stress (beta
      = -.069, p = .010) with mastery as related to baseline CRP levels. Both measures
      were associated with higher CRP at low (beta = .102, p = .003; beta = .088, p =
      .015) but not high levels of mastery. In addition, chronic stress interacted with
      baseline mastery (beta = .056, p = .011) and change in mastery (beta = -.056, p =
      .016) to predict 4-year change in CRP. Chronic stress was associated with an
      increase in CRP at high baseline mastery (beta = .071, p = .022) and when mastery
      decreased during follow-up (beta = .088, p = .011). There were no main effects of
      stress or control variables other than an association of constraints with a
      larger increase in CRP (beta = .062, p = .017). Interactions were minimally
      attenuated (<15%) upon further adjustment for negative affect, body mass index,
      smoking, and physical activity. CONCLUSIONS: High mastery may protect against
      elevated systemic inflammation associated with substantial lifetime trauma
      exposure. Individuals who experience declines in mastery may be most susceptible
      to increases in inflammation associated with chronic stress.

PMID- 28437380
TI  - Lifestyle and Neurocognition in Older Adults With Cardiovascular Risk Factors and
      Cognitive Impairment.
AB  - OBJECTIVE: The aim of the study was to determine the relationship of lifestyle
      factors and neurocognitive functioning in older adults with vascular risk factors
      and cognitive impairment, no dementia (CIND). METHODS: One hundred sixty adults
      (M [SD] = 65.4 [6.8] years) with CIND completed neurocognitive assessments of
      executive function, processing speed, and memory. Objective measures of physical
      activity using accelerometry, aerobic capacity determined by exercise testing,
      and dietary habits quantified by the Food Frequency Questionnaire and 4-Day Food
      Diary to assess adherence to the Mediterranean and Dietary Approaches to Stop
      Hypertension (DASH) diets were obtained to assess direct effects with
      neurocognition. Potential indirect associations of high-sensitivity C-reactive
      protein and the Framingham Stroke Risk Profile also were examined. RESULTS:
      Greater aerobic capacity (beta = 0.24) and daily physical activity (beta = 0.15)
      were associated with better executive functioning/processing speed and verbal
      memory (betas = 0.24; 0.16). Adherence to the DASH diet was associated with
      better verbal memory (beta = 0.17). Greater high-sensitivity C-reactive protein
      (betas = -0.14; -0.21) and Framingham Stroke Risk Profile (beta = -0.18; -0.18)
      were associated with poorer executive functioning/processing speed and verbal
      memory. Greater stroke risk partially mediated the association of aerobic
      capacity with executive functioning/processing speed, and verbal memory and
      greater inflammation partially mediated the association of physical activity and
      aerobic fitness, with verbal memory. CONCLUSIONS: Higher levels of physical
      activity, aerobic fitness, and adherence to the DASH diet are associated with
      better neurocognitive performance in adults with CIND. These findings suggest
      that the adoption of healthy lifestyle habits could reduce the risk of
      neurocognitive decline in vulnerable older adults. CLINICAL TRIAL REGISTRATION:
      NCT01573546.

PMID- 28437381
TI  - Mean Levels and Variability in Affect, Diabetes Self-Care Behaviors, and
      Continuously Monitored Glucose: A Daily Study of Latinos With Type 2 Diabetes.
AB  - OBJECTIVE: This study investigated between- and within-person associations among
      mean levels and variability in affect, diabetes self-care behaviors, and
      continuously monitored glucose in Latinos with type 2 diabetes. METHODS: Fifty
      participants (M [SD] age = 57.8 [11.7] years, 74% women, mean [SD] glycosylated
      hemoglobin A1c = 8.3% [1.5%]) wore a "blinded" continuous glucose monitor for 7
      days, and they responded to twice daily automated phone surveys regarding
      positive affect, negative affect, and self-care behaviors. RESULTS: Higher mean
      levels of NA were associated with higher mean glucose (r = .30), greater percent
      hyperglycemia (r = .34) and greater percentage of out-of-range glucose (r = .34).
      Higher NA variability was also related to higher mean glucose (r = .34), greater
      percent of hyperglycemia (r = .44) and greater percentage of out-of-range glucose
      (r = .43). Higher positive affect variability was related to lower percentage of
      hypoglycemia (r = -.33). Higher mean levels of self-care behaviors were related
      to lower glucose variability (r = -.35). Finally, higher self-care behavior
      variability was related to greater percentage of hyperglycemia (r = .31) and
      greater percentage of out-of-range glucose (r = -.28). In multilevel regression
      models, within-person increases from mean levels of self-care were associated
      with lower mean levels of glucose (b = -7.4, 95% confidence interval [CI] = -12.8
      to -1.9), lower percentage of hyperglycemia (b = -0.04, 95% CI = -0.07 to -0.01),
      and higher percentage of hypoglycemia (b = 0.02, 95% CI = 0.01 to 0.03) in the
      subsequent 10-hour period. CONCLUSIONS: Near-to-real time sampling documented
      associations of glucose with affect and diabetes self-care that are not
      detectable with traditional measures.

PMID- 28437382
TI  - Organ Transplantation in Australia.

PMID- 28437384
TI  - Epigenetic Remodeling in Exhausted T Cells: Implications for Transplantation
      Tolerance.

PMID- 28437385
TI  - Before or After Transplantation? A Review of the Cost Effectiveness of Treating
      Waitlisted Patients With Hepatitis C.
AB  - All patients with chronic hepatitis C virus (HCV) infections can and should be
      treated. Though highly effective direct-acting antiviral therapies are costly,
      the price of a cure is a 1-time investment that is outweighed by future benefits.
      For clinicians caring for patients requiring liver transplant, the key question
      relates to the timing of treatment: before or after liver transplantation? On 1
      hand, treating HCV often improves our patients' model for end-stage liver disease
      (MELD) score, decreasing costs, and potentially improving longevity by reducing
      our patients' risk of death and transplantation. On the other hand, there is a
      concern that the cured patient with decompensated cirrhosis will find themselves
      in "MELD purgatory" with nonprogressive liver disease but a poor quality of life.
      At the same time, some patients, such as those with hepatocellular carcinoma,
      will require liver transplant irrespective of their MELD meaning that
      pretransplant therapy cannot reduce costs in such settings. These important
      tradeoffs are often difficult reconcile for clinicians who care for patients
      awaiting liver transplant. Fortunately, guidance for navigating these competing
      concerns can be obtained from cost-effectiveness analyses. Herein, we review the
      available data on this approach to HCV therapy before or after liver transplant.

PMID- 28437386
TI  - The International Liver Transplantation Society Living Donor Liver Transplant
      Recipient Guideline.
AB  - Living donor liver transplantation (LDLT) has been increasingly embraced around
      the world as an important strategy to address the shortage of deceased donor
      livers. The aim of this guideline, approved by the International Liver
      Transplantation Society (ILTS), is to provide a collection of expert opinions,
      consensus, and best practices surrounding LDLT. Recommendations were developed
      from an analysis of the National Library of Medicine living donor transplantation
      indexed literature using the Grading of Recommendations Assessment, Development
      and Evaluation methodology. Writing was guided by the ILTS Policy on the
      Development and Use of Practice Guidelines (www.ilts.org). Intended for use by
      physicians, these recommendations support specific approaches to the diagnostic,
      therapeutic, and preventive aspects of care of living donor liver transplant
      recipients.

PMID- 28437387
TI  - International Liver Transplantation Society Consensus Statement on Hepatitis C
      Management in Liver Transplant Candidates.

PMID- 28437388
TI  - International Liver Transplantation Society Consensus Statement on Hepatitis C
      Management in Liver Transplant Recipients.

PMID- 28437390
TI  - Hepatitis C-Positive Kidney Transplant Recipients-When Is The Best Time to Treat
      With Direct-Acting Antiviral Agents?

PMID- 28437389
TI  - Normothermic Perfusion in the Assessment and Preservation of Declined Livers
      Before Transplantation: Hyperoxia and Vasoplegia-Important Lessons From the First
      12 Cases.
AB  - BACKGROUND: A program of normothermic ex situ liver perfusion (NESLiP) was
      developed to facilitate better assessment and use of marginal livers, while
      minimizing cold ischemia. METHODS: Declined marginal livers and those offered for
      research were evaluated. Normothermic ex situ liver perfusion was performed using
      an erythrocyte-based perfusate. Viability was assessed with reference to
      biochemical changes in the perfusate. RESULTS: Twelve livers (9 donation after
      circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index
      2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes)
      after an initial cold storage period of 427 minutes (range, 222-877 minutes). The
      first 6 livers were perfused at high perfusate oxygen tensions, and the
      subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the
      first 6 recipients developed postreperfusion syndrome and 4 had sustained
      vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a
      difficult explant. The subsequent 6 liver transplants, with livers perfused at
      lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients
      developed cholangiopathy, and this was associated with an inability to produce an
      alkali bile during NESLiP. CONCLUSIONS: Normothermic ex situ liver perfusion
      enabled assessment and transplantation of 12 livers that may otherwise not have
      been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion
      syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile
      production, may be important in determining the likelihood of posttransplant
      cholangiopathy. Normothermic ex situ liver perfusion has the potential to
      increase liver utilization, but more work is required to define factors
      predicting good outcomes.

PMID- 28437391
TI  - Predictive Value of Preoperative Neutrophil Lymphocyte Ratio in Determining the
      Stage of Gastric Tumor.
AB  - BACKGROUND Neutrophil-lymphocyte ratio (NLR) is an indicator of the inflammatory
      state, and its increase has been shown to be a negative prognostic factor for
      many malignancies. The aim of this study was to determine whether there was a
      relationship between NLR and tumor aggressiveness in gastric cancer patients and
      to investigate the prognostic significance of NLR. MATERIAL AND METHODS The
      medical records of 189 patients with gastric cancer between January 2009 and
      January 2014 were examined for the presence of metastasis, tumor staging, tumor
      differentiation grade, and preoperative NLR value. RESULTS Of the 189 patients,
      61 were female (32.2%) and 128 were male (67.7%). Eight-eight patients had NLR
      values of four or higher. A comparison of the high NLR value group and the low
      NLR value group found no statistically significant difference for
      clinicopathological features of age, gender, type of operation, of degree of
      differentiation; differences ranged from 20.7% to 46.2%, p<0.001. CONCLUSIONS
      Increase in NLR has been associated with poor prognosis in univariate analysis
      and variations of this parameter have also been shown to be correlated with tumor
      progression. NLR values should be considered as a useful follow-up parameter.

PMID- 28437392
TI  - Should we administer oxygen during an acute coronary syndrome?
AB  - Oxygen therapy is used for the treatment of acute coronary syndrome without
      further discussion. However, the support of this practice in clinical research is
      scarce, ignoring the true effects of its implementation. To answer this question,
      we searched in Epistemonikos database, which is maintained by screening multiple
      information sources. We identified five systematic reviews including 12 studies
      overall, five of which were randomized trials. We extracted data, conducted a
      meta-analysis and generated a summary of findings table using the GRADE approach.
      We concluded that using oxygen probably does not decrease pain, and might not
      make any difference in mortality during an acute coronary syndrome.

PMID- 28437393
TI  - Protein degradation: DCAFinating splicing.

PMID- 28437394
TI  - Selective degradation of splicing factor CAPERalpha by anticancer sulfonamides.
AB  - Target-protein degradation is an emerging field in drug discovery and
      development. In particular, the substrate-receptor proteins of the cullin
      ubiquitin ligase system play a key role in selective protein degradation, which
      is an essential component of the anti-myeloma activity of immunomodulatory drugs
      (IMiDs), such as lenalidomide. Here, we demonstrate that a series of anticancer
      sulfonamides NSC 719239 (E7820), indisulam, and NSC 339004 (chloroquinoxaline
      sulfonamide, CQS) induce proteasomal degradation of the U2AF-related splicing
      factor coactivator of activating protein-1 and estrogen receptors (CAPERalpha)
      via CRL4DCAF15 mediated ubiquitination in human cancer cell lines. Both CRISPR
      Cas9-based knockout of DCAF15 and a single amino acid substitution of CAPERalpha
      conferred resistance against sulfonamide-induced CAPERalpha degradation and cell
      growth inhibition. Thus, these sulfonamides represent selective chemical probes
      for disrupting CAPERalpha function and designate DCAFs as promising drug targets
      for promoting selective protein degradation in cancer therapy.

PMID- 28437396
TI  - Immunology: Mind the immuno-connection gap.

PMID- 28437397
TI  - Building a Better Battery.

PMID- 28437398
TI  - Letters.

PMID- 28437399
TI  - High Robot.

PMID- 28437400
TI  - The Global Warming Wild Card.

PMID- 28437401
TI  - Recommended.

PMID- 28437395
TI  - Global survey of the immunomodulatory potential of common drugs.
AB  - Small-molecule drugs may complement antibody-based therapies in an immune
      oncology setting, yet systematic methods for the identification and
      characterization of the immunomodulatory properties of these entities are
      lacking. We surveyed the immumomodulatory potential of 1,402 small chemical
      molecules, as defined by their ability to alter the cell-cell interactions among
      peripheral mononuclear leukocytes ex vivo, using automated microscopy and
      population-wide single-cell image analysis. Unexpectedly, ~10% of the agents
      tested affected these cell-cell interactions differentially. The results
      accurately recapitulated known immunomodulatory drug classes and revealed several
      clinically approved drugs that unexpectedly harbor the ability to modulate the
      immune system, which could potentially contribute to their physiological
      mechanism of action. For instance, the kinase inhibitor crizotinib promoted T
      cell interactions with monocytes, as well as with cancer cells, through
      inhibition of the receptor tyrosine kinase MSTR1 and subsequent upregulation of
      the expression of major histocompatibility complex molecules. The approach offers
      an attractive platform for the personalized identification and characterization
      of immunomodulatory therapeutics.

PMID- 28437402
TI  - Don't Pass the Weed or Say "Guns".

PMID- 28437403
TI  - Schizophrenia's Unyielding Mysteries.

PMID- 28437404
TI  - Home Sweet Dome.

PMID- 28437405
TI  - A March for Science Is Not Enough.

PMID- 28437406
TI  - Bilingual Brains Remember.

PMID- 28437407
TI  - The Elusive Northwest Passage.

PMID- 28437408
TI  - Aspirin vs. Cancer.

PMID- 28437409
TI  - 50, 100 &150 Years Ago.

PMID- 28437410
TI  - How to Build a Dog.

PMID- 28437412
TI  - Nuclear Ghosts.

PMID- 28437411
TI  - Soil in the Forecast.

PMID- 28437413
TI  - Missing Links.

PMID- 28437414
TI  - Green Hydrogen.

PMID- 28437416
TI  - On Witches and Terrorists.

PMID- 28437415
TI  - Dawn of Innovation.

PMID- 28437417
TI  - A Spare Hand.

PMID- 28437418
TI  - Strange News from Another Star.

PMID- 28437419
TI  - Dissent with Modification.

PMID- 28437421
TI  - The New Origins of Technology.

PMID- 28437420
TI  - Maps on the Move.

PMID- 28437422
TI  - The War on Facts Undermines Democracy.

PMID- 28437423
TI  - Quick Hits.

PMID- 28437424
TI  - Of Meat and Men.

PMID- 28437425
TI  - Split-Second Reactions.

PMID- 28437426
TI  - Representational models: A common framework for understanding encoding, pattern
      component, and representational-similarity analysis.
AB  - Representational models specify how activity patterns in populations of neurons
      (or, more generally, in multivariate brain-activity measurements) relate to
      sensory stimuli, motor responses, or cognitive processes. In an experimental
      context, representational models can be defined as hypotheses about the
      distribution of activity profiles across experimental conditions. Currently,
      three different methods are being used to test such hypotheses: encoding
      analysis, pattern component modeling (PCM), and representational similarity
      analysis (RSA). Here we develop a common mathematical framework for understanding
      the relationship of these three methods, which share one core commonality: all
      three evaluate the second moment of the distribution of activity profiles, which
      determines the representational geometry, and thus how well any feature can be
      decoded from population activity. Using simulated data for three different
      experimental designs, we compare the power of the methods to adjudicate between
      competing representational models. PCM implements a likelihood-ratio test and
      therefore provides the most powerful test if its assumptions hold. However, the
      other two approaches-when conducted appropriately-can perform similarly. In
      encoding analysis, the linear model needs to be appropriately regularized, which
      effectively imposes a prior on the activity profiles. With such a prior, an
      encoding model specifies a well-defined distribution of activity profiles. In
      RSA, the unequal variances and statistical dependencies of the dissimilarity
      estimates need to be taken into account to reach near-optimal power in inference.
      The three methods render different aspects of the information explicit (e.g.
      single-response tuning in encoding analysis and population-response
      representational dissimilarity in RSA) and have specific advantages in terms of
      computational demands, ease of use, and extensibility. The three methods are
      properly construed as complementary components of a single data-analytical
      toolkit for understanding neural representations on the basis of multivariate
      brain-activity data.

PMID- 28437427
TI  - Bacterial diversity of bacteriomes and organs of reproductive, digestive and
      excretory systems in two cicada species (Hemiptera: Cicadidae).
AB  - Cicadas form intimate symbioses with bacteria to obtain nutrients that are scarce
      in the xylem fluid they feed on. The obligate symbionts in cicadas are
      purportedly confined to specialized bacteriomes, but knowledge of bacterial
      communities associated with cicadas is limited. Bacterial communities in the
      bacteriomes and organs of reproductive, digestive and excretory systems of two
      cicada species (Platypleura kaempferi and Meimuna mongolica) were investigated
      using different methods, and the bacterial diversity and distribution patterns of
      dominant bacteria in different tissues were compared. Within each species, the
      bacterial communities of testes are significantly different from those of
      bacteriomes and ovaries. The dominant endosymbiont Candidatus Sulcia muelleri is
      found not only in the bacteriomes and reproductive organs, but also in the
      "filter chamber + conical segment" of both species. The transmission mode of this
      endosymbiont in the alimentary canal and its effect on physiological processes
      merits further study. A novel bacterium of Rhizobiales, showing ~80% similarity
      to Candidatus Hodgkinia cicadicola, is dominant in the bacteriomes and ovaries of
      P. kaempferi. Given that the genome of H. cicadicola exhibits rapid sequence
      evolution, it is possible that this novel bacterium is a related endosymbiont
      with beneficial trophic functions similar to that of H. cicadicola in some other
      cicadas. Failure to detect H. cicadicola in M. mongolica suggests that it has
      been subsequently replaced by another bacterium, a yeast or gut microbiota which
      compensates for the loss of H. cicadicola. The distribution of this novel
      Rhizobiales species in other cicadas and its identification require further
      investigation to help establish the definition of the bacterial genus Candidatus
      Hodgkinia and to provide more information on sequence divergence of related
      endosymbionts of cicadas. Our results highlight the complex bacterial communities
      of cicadas, and are informative for further studies of the interactions and co
      evolution of insect-microbial symbioses in Cicadoidea.

PMID- 28437428
TI  - Prevalence of alcohol use disorders among under- and post-graduate healthcare
      students in Italy.
AB  - A cross-sectional study was carried out on 641 medical students, 359 students
      attending a degree course in the healthcare professions, and 500 resident
      physicians, all undergoing health surveillance at the ambulatory of the Division
      of Occupational Medicine, Second University of Naples, Italy. 76.1% of the
      participants drank alcohol, with 85.5% of medical students, 77.4% of resident
      physicians, and 63% of healthcare-professions students reporting regular alcohol
      use. In the whole sample, the mean Audit-C score was 1.6 for men and 1.1 for
      women; only 5.5% of men and 7.1% of women had a hazardous alcohol consumption
      with an Audit-C score of respectively >=4 and >=3. Multivariate regression
      modeling revealed that regular alcohol use was more likely in individuals who
      were men, were younger, had a lower body-mass index, were active smokers, were
      habitual coffee drinkers, and who were resident physicians or medical students
      rather than healthcare-professions students. This finding identifies a need to
      assess alcohol use in medical-profession workers in order to identify risky
      behavior early on and to carry out rapidly effective preventive and curative
      interventions.

PMID- 28437429
TI  - Correction: Plasma Concentrations Predict Aortic Expression of Growth-Arrest
      Specific Protein 6 in Patients Undergoing Coronary Artery Bypass Grafting.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0079452.].

PMID- 28437430
TI  - Cerebellar volume as imaging outcome in progressive multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: To assess whether cerebellar volumes changes could
      represent a sensitive outcome measure in primary-progressive MS. MATERIAL AND
      METHODS: Changes in cerebellar volumes over one-year follow-up, estimated in 26
      primary-progressive MS patients and 20 controls with Freesurfer longitudinal
      pipeline, were assessed using Wilcoxon test and tested for their correlation with
      disability worsening by a logistic regression. Clinical worsening was defined as
      EDSS score increase or change of >20% for 25-foot walk test or 9-hole peg test
      scores at follow-up. Sample sizes for given treatment effects and power were
      calculated. The findings were validated in an independent cohort of 20 primary
      progressive MS patients. RESULTS: Significant changes were detected in brain T1
      lesion volume (p<0.01), cerebellar T2 and T1 lesion volume (p<0.01 and p<0.05),
      cerebellar volume, cerebellar cortex volume, and cerebellar WM volume (p<0.001).
      Only cerebellar volume and cerebellar cortex volume percentage change were
      significantly reduced in clinically progressed patients when compared to patients
      who did not progress (p<0.01; respectively AUC of 0.91 and 0.96). Cerebellar
      volume percentage changes were consistent in the exploration and validation
      cohorts (cerebellar volume -1.90+/-1.11% vs -1.47+/-2.30%; cerebellar cortex
      volume -1.68+/-1.41% vs -1.56+/-2.23%). Based on our results the numbers of
      patients required to detect a 30% effect are 81 per arm for cerebellar volume and
      162 per arm for cerebellar cortex volume (90% power, type 1 error alpha = 0.05).
      CONCLUSIONS: Our results suggest a role for cerebellar cortex volume and
      cerebellar volume as potential short-term imaging metrics to monitor treatment
      effect in primary-progressive MS clinical trials.

PMID- 28437431
TI  - Factors associated with acquired Anti IFN- gamma autoantibody in patients with
      nontuberculous mycobacterial infection.
AB  - BACKGROUND: The clinical syndrome of disseminated nontuberculous mycobacterial
      (NTM) infection in patients who were previously healthy is now well recognized to
      be associated with an acquired autoantibody to Interferon gamma (Anti IFN- gamma
      autoantibody). However, the risk factors of this syndrome remain unknown. METHOD:
      We performed an unmatched case control study among patients with NTM diseases who
      were diagnosed and treated at Siriraj Hospital, Bangkok, Thailand. Anti-IFN
      autoantibody was detected by enzyme-linked immunosorbent assay (ELISA) method.
      Cases were patients with NTM diseases and detectable anti IFN- gamma
      autoantibody. Controls were randomly selected from those with undetectable anti
      IFN- gamma autoantibody. Data from both groups including demographic data,
      clinical presentation, laboratory results, other risk factors and HLA genotypes
      were collected. Univariate and multivariate analyses were performed to identify
      independent risk factors for this syndrome. RESULTS: 70 cases (mean age 50 +/- 11
      years) and 70 controls (mean age 58 +/- 18 years) were enrolled into the study.
      Mycobacterial abscessus was the most common NTM pathogen found in both groups
      (72.9% in cases and 41.4% in controls respectively). However, disseminated NTM
      disease was significantly more common in cases (92.9%) than in the controls
      (14.3%, p<0.001). Binary logistic regression analysis showed that previous OIs
      (adjusted OR14.87, 95% CI 2.36-93.86), birthplace outside Central region
      (adjusted OR 19.19, 95% CI 3.86-95.35), lack of comorbidities lead to
      immunosuppression, such as HIV infection or diabetes mellitus (adjusted OR 23.68,
      95% CI 4.01-139.94), and presence of HLA DRB1*15/16 (adjusted OR 153.28, 95% CI
      16.87-139.88) were independent factors associated with this syndrome. CONCLUSION:
      Patients with NTM disease associated with anti IFN- gamma autoantibody are almost
      always previously healthy and HIV negative. Most of these patients presented with
      disseminated NTM disease with generalized lymphadenitis and often with reactive
      skin lesions. Factors associated with detectable anti IFN- gamma autoantibody are
      HLA-DRB1 and DQB1 alleles, and history of previous OIs in patients without
      comorbidity that leads to immunosuppression. Further studies are needed to better
      understand these associations and to improve the treatment outcome.

PMID- 28437433
TI  - Retraction: Loss of a Conserved tRNA Anticodon Modification Perturbs Plant
      Immunity.

PMID- 28437432
TI  - Genome-wide identification and expression analysis of calcium-dependent protein
      kinase and its related kinase gene families in melon (Cucumis melo L.).
AB  - The calcium-dependent protein kinase (CDPK) is a ser/thr protein kinase that
      plays vital roles in plant growth, development, and responses to multiple
      stresses. Despite an important member of the stress responsive gene family,
      little is known about the evolutionary history and expression patterns of CDPK
      genes in melon. Herein, a total of 18 CDPK genes and 7 CDPK-related protein
      kinases (CRK) genes were identified in the melon genome via bioinformatic
      analysis, which were unevenly distributed across eleven chromosomes with an
      apparent exception for chromosome 3. Comparative syntenic analysis between
      Cucumis melo L. and Arabidopsis thaliana revealed that 13 CmCDPKs and 19 AtCPKs
      existed in 20 corresponding syntenic blocks. In addition, based on gene structure
      and phylogenetic analyses, all CmCDPKs were divided into four groups (CDPK I-IV)
      and CmCRKs clustered into one group (CRK I). Interestingly, group CDPK IV was
      clearly distinct from the other three CDPK groups, but clustered with CRK I on
      the phylogenetic tree, implying their origination from a common ancestor.
      Furthermore, CmCDPKand CmCRK genes were differentially expressed in response to
      various stimuli, such as biotic stress (Podosphaera xanthii), abiotic stress
      (salt and cold), and hormone (abscisic acid) treatment. To our knowledge, this is
      the first report on CDPK and CRK gene families in melon, which provides a basic
      foundation for functional characterizations of CmCDPK and CmCRK genes in the
      future.

PMID- 28437434
TI  - Comparisons of GnRH antagonist protocol versus GnRH agonist long protocol in
      patients with normal ovarian reserve: A systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of gonadotropin-releasing
      hormone antagonist (GnRH-ant) protocol and gonadotropin-releasing hormone agonist
      (GnRH-a) long protocol in patients with normal ovarian reserve. METHODS: We
      searched the PubMed (1992-2016), Cochrane Library (1999-2016), Web of Science
      (1950-2016), Chinese Biomedical Database (CBM, 1979-2016), and China National
      Knowledge Infrastructure (CNKI, 1994-2016). Any randomized controlled trials
      (RCTs) that compared GnRH-ant protocol and GnRH-a long protocol in patients with
      normal ovarian reserve were included, and data were extracted independently by
      two reviewers. The meta-analysis was performed by Revman 5.3 software. RESULTS:
      Twenty-nine RCTs (6399 patients) were included in this meta-analysis. Stimulation
      days (mean difference (MD) [95% confidence interval (CI)] = -0.8 [-1.36, -0.23],
      P = 0.006), gonadotrophin (Gn) dosage (MD [95% CI] = -3.52 [-5.56, -1.48], P =
      0.0007), estradiol (E2) level on the day of human chorionic gonadotrophin (HCG)
      administration (MD [95% CI] = -365.49 [-532.93, -198.05], P<0.0001), the number
      of oocytes retrieved (MD [95% CI] = -1.41 [-1.84, -0.99], P<0.00001), the embryos
      obtained (MD [95% CI] = -0.99 [-1.38, -0.59], P<0.00001), incidence of ovarian
      hyperstimulation syndrome (OHSS) (OR [95% CI] = 0.69 [0.57, 0.83], P<0.0001) were
      statistically significantly lower in GnRH-ant protocol than GnRH-a long protocol.
      However, the clinical pregnancy rate (OR [95% CI] = 0.90 [0.80, 1.01], P = 0.08),
      ongoing pregnancy rate (OR [95% CI] = 0.88 [0.77, 1.00], P = 0.05), live birth
      rate (OR [95% CI] = 0.95 [0.74, 1.09], P = 0.27), miscarriage rate (OR [95% CI] =
      0.98 [0.69, 1.40], P = 0.93), and cycle cancellation rate (OR [95% CI] = 0.86
      [0.52, 1.44], P = 0.57) showed no significant differences between the two groups.
      CONCLUSION: GnRH-ant protocol substantially decreased the incidence of OHSS
      without influencing the pregnancy rate and live birth rate compared to GnRH-a
      long protocol among patients with normal ovarian reserve.

PMID- 28437435
TI  - Infective respiratory syncytial virus is present in human cord blood samples and
      most prevalent during winter months.
AB  - BACKGROUND: Human respiratory syncytial virus (RSV) remains the most common cause
      of severe lower respiratory tract disease amongst infants, and continues to cause
      annual epidemics of respiratory disease every winter worldwide. Demonstrating
      placental transmission of viable RSV in human samples is a major paradigm shift
      in respiratory routes considered likely for RSV transmission. METHODS: Droplet
      digital PCR (ddPCR) was used to identify RSV present in cord blood
      mononucleocytes (CBM). CBMs testing positive for RSV were treated with
      phytohemagglutinin (PHA), PHA and nitric oxide (NO) or PHA, NO and palivizumab,
      and co-cultured with HeLa cell monolayers. Subsequent immuno-staining for RSV was
      used to visualize infective viral plaques. RESULTS: RSV was detected in 26 of 45
      samples (57.7%) by ddPCR. CBM's collected in winter were more likely to test
      positive for RSV (17/21 samples, risk = 80%, OR = 7.08; 95% CI 1.80-27.80; p =
      0.005) compared to non-winter months (9/24 samples, 37.5%). RSV plaques were
      observed in non-treated and treated co-cultured HeLa monolayers. CONCLUSIONS:
      Demonstrating active RSV in CBMs suggests in utero transmission of infective
      virus to the fetus without causing overt disease. This is likely to have an
      important impact on immune development as well as future virus-host interactions,
      thereby warranting further investigation.

PMID- 28437436
TI  - Intrinsically-generated fluctuating activity in excitatory-inhibitory networks.
AB  - Recurrent networks of non-linear units display a variety of dynamical regimes
      depending on the structure of their synaptic connectivity. A particularly
      remarkable phenomenon is the appearance of strongly fluctuating, chaotic activity
      in networks of deterministic, but randomly connected rate units. How this type of
      intrinsically generated fluctuations appears in more realistic networks of
      spiking neurons has been a long standing question. To ease the comparison between
      rate and spiking networks, recent works investigated the dynamical regimes of
      randomly-connected rate networks with segregated excitatory and inhibitory
      populations, and firing rates constrained to be positive. These works derived
      general dynamical mean field (DMF) equations describing the fluctuating dynamics,
      but solved these equations only in the case of purely inhibitory networks. Using
      a simplified excitatory-inhibitory architecture in which DMF equations are more
      easily tractable, here we show that the presence of excitation qualitatively
      modifies the fluctuating activity compared to purely inhibitory networks. In
      presence of excitation, intrinsically generated fluctuations induce a strong
      increase in mean firing rates, a phenomenon that is much weaker in purely
      inhibitory networks. Excitation moreover induces two different fluctuating
      regimes: for moderate overall coupling, recurrent inhibition is sufficient to
      stabilize fluctuations; for strong coupling, firing rates are stabilized solely
      by the upper bound imposed on activity, even if inhibition is stronger than
      excitation. These results extend to more general network architectures, and to
      rate networks receiving noisy inputs mimicking spiking activity. Finally, we show
      that signatures of the second dynamical regime appear in networks of integrate
      and-fire neurons.

PMID- 28437437
TI  - Use of short interfering RNA delivered by cationic liposomes to enable efficient
      down-regulation of PTPN22 gene in human T lymphocytes.
AB  - Type 1 diabetes and thyroid disease are T cell-dependent autoimmune
      endocrinopathies. The standard substitutive administration of the deficient
      hormones does not halt the autoimmune process; therefore, development of
      immunotherapies aiming to preserve the residual hormonal cells, is of crucial
      importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine
      phosphatase variant, plays a potential pathophysiological role in autoimmunity.
      The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor
      signaling; R620W variant, leading to a gain of function with paradoxical reduced
      T cell activation, may represent a valid therapeutic target. We aimed to develop
      novel wild type PTPN22 short interfering RNA duplexes (siRNA) and optimize their
      delivery into Jurkat T cells and PBMC by using liposomal carriers. Conformational
      stability, size and polydispersion of siRNA in lipoplexes was measured by CD
      spectroscopy and DLS. Lipoplexes internalization and toxicity evaluation was
      assessed by confocal microscopy and flow cytometry analysis. Their effect on Lyp
      expression was evaluated by means of Western Blot and confocal microscopy.
      Functional assays through engagement of TCR signaling were established to
      evaluate biological consequences of down-modulation. Both Jurkat T cells and PBMC
      were efficiently transfected by stable custom lipoplexes. Jurkat T cell
      morphology and proliferation was not affected. Lipoplexes incorporation was
      visualized in CD3+ but also in CD3- peripheral blood immunotypes without signs of
      toxicity, damage or apoptosis. Efficacy in affecting Lyp protein expression was
      demonstrated in both transfected Jurkat T cells and PBMC. Moreover, impairment of
      Lyp inhibitory activity was revealed by increase of IL-2 secretion in culture
      supernatants of PBMC following anti-CD3/CD28 T cell receptor-driven stimulation.
      The results of our study open the pathway to future trials for the treatment of
      autoimmune diseases based on the selective inhibition of variant PTPN22 allele
      using lipoplexes of siRNA antisense oligomers.

PMID- 28437438
TI  - Use of the MATRICS consensus cognitive battery (MCCB) to evaluate cognitive
      deficits in bipolar disorder: A systematic review and meta-analysis.
AB  - BACKGROUND: The Measurement and Treatment Research to Improve Cognition
      Schizophrenia Consensus Cognitive Battery (MCCB) has also been proposed for use
      in clinical trials to assess cognitive deficits in patients with bipolar disorder
      (BD). The aim of this study was to evaluate cognitive function assessed by the
      MCCB in BD. METHODS: A literature search of the PubMed, Embase, PsycINFO, SCI,
      Cochrane Library databases and the Cochrane Controlled Trials Register was
      conducted. Case reports, reviews and meta-analyses were excluded and a systematic
      review of the remaining studies of cognitive function in BD was carried out. The
      cognitive outcome measure was the MCCB, including 7 domains and overall
      cognition. A random-effects model was applied. RESULTS: Eighty eight studies were
      initially identified. Seven clinical studies comprising a total of 487 patients
      and 570 healthy controls (HC) were included in the meta-analysis. Patients with
      BD performed worse than HC in overall cognition and processing speed with a large
      effect size of >0.8; with a medium effect size (0.5-0.8) in attention, working
      memory, verbal learning and visual learning; and with a small effect size (0.2
      0.5) in reasoning and problem solving and social cognition. CONCLUSION: Patients
      with BD performed worse than HC in overall cognition and all cognitive domains of
      the MCCB. Cognitive deficits in domains of processing speed and working memory
      are prominent in patients with BD. Our findings suggest that MCCB can be usefully
      applied in BD.

PMID- 28437440
TI  - Synthesizer: Expediting synthesis studies from context-free data with information
      retrieval techniques.
AB  - Scientists have unprecedented access to a wide variety of high-quality datasets.
      These datasets, which are often independently curated, commonly use unstructured
      spreadsheets to store their data. Standardized annotations are essential to
      perform synthesis studies across investigators, but are often not used in
      practice. Therefore, accurately combining records in spreadsheets from differing
      studies requires tedious and error-prone human curation. These efforts result in
      a significant time and cost barrier to synthesis research. We propose an
      information retrieval inspired algorithm, Synthesize, that merges unstructured
      data automatically based on both column labels and values. Application of the
      Synthesize algorithm to cancer and ecological datasets had high accuracy (on the
      order of 85-100%). We further implement Synthesize in an open source web
      application, Synthesizer (https://github.com/lisagandy/synthesizer). The software
      accepts input as spreadsheets in comma separated value (CSV) format, visualizes
      the merged data, and outputs the results as a new spreadsheet. Synthesizer
      includes an easy to use graphical user interface, which enables the user to
      finish combining data and obtain perfect accuracy. Future work will allow
      detection of units to automatically merge continuous data and application of the
      algorithm to other data formats, including databases.

PMID- 28437439
TI  - Landscape and environmental influences on Mycobacterium ulcerans distribution
      among aquatic sites in Ghana.
AB  - Buruli ulcer, caused by Mycobacterium ulcerans, is highly endemic in West Africa.
      While the mode of transmission is unknown, many studies associate Buruli ulcer
      with different types of water exposure. We present results from the largest study
      to date to test for M. ulcerans in aquatic sites and identify environmental
      attributes associated with its presence. Environmental samples from 98 aquatic
      sites in the Greater Accra, Ashanti, and Volta regions of Ghana were tested for
      the presence of M. ulcerans DNA by polymerase chain reaction. The proportion of
      aquatic sites positive for M. ulcerans varied by region: Ashanti 66% (N = 39),
      Greater Accra 34% (N = 29), and Volta 0% (N = 30). We explored the spatial
      distribution of M. ulcerans positive and negative water bodies and found no
      significant clusters. We also determined both highly localized water attributes
      and broad scale remotely sensed land cover and terrain environmental
      characteristics associated with M. ulcerans presence through logistic regression.
      Our results concur with published results regarding conditions suitable for M.
      ulcerans growth and associations with Buruli ulcer disease burden with regards to
      water characteristics and disturbed environments, but differ from others with
      regards to spatial associations and topographic effects such as elevation and
      wetness. While our results suggest M. ulcerans is an environmental organism
      existing in a specific ecological niche, they also reveal variation in the
      elements defining this niche across the sites considered. In addition, despite
      the causal association between Buruli ulcer and M. ulcerans, we observed no
      significant statistical association between case reports of Buruli ulcer and
      presence of M. ulcerans in nearby waterbodies.

PMID- 28437441
TI  - Fluorescence Imaging Topography Scanning System for intraoperative multimodal
      imaging.
AB  - Fluorescence imaging is a powerful technique with diverse applications in
      intraoperative settings. Visualization of three dimensional (3D) structures and
      depth assessment of lesions, however, are oftentimes limited in planar
      fluorescence imaging systems. In this study, a novel Fluorescence Imaging
      Topography Scanning (FITS) system has been developed, which offers color
      reflectance imaging, fluorescence imaging and surface topography scanning
      capabilities. The system is compact and portable, and thus suitable for
      deployment in the operating room without disturbing the surgical flow. For system
      performance, parameters including near infrared fluorescence detection limit,
      contrast transfer functions and topography depth resolution were characterized.
      The developed system was tested in chicken tissues ex vivo with simulated tumors
      for intraoperative imaging. We subsequently conducted in vivo multimodal imaging
      of sentinel lymph nodes in mice using FITS and PET/CT. The PET/CT/optical
      multimodal images were co-registered and conveniently presented to users to guide
      surgeries. Our results show that the developed system can facilitate multimodal
      intraoperative imaging.

PMID- 28437442
TI  - Relationship between early onset severe intrahepatic cholestasis of pregnancy and
      higher risk of meconium-stained fluid.
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is the commonest
      gestational liver disease. The risk of adverse fetal outcome has been associated
      with the severity of maternal hypercholanemia after diagnosis. OBJECTIVE: To
      investigate whether there is a relationship between the severity and timing of
      onset of hypercholanemia and the risk of meconium-stained amniotic fluid (MSAF)
      and adverse neonatal events. STUDY DESIGN: The study included 382 pregnancies
      complicated by ICP managed at a referral hospital in Buenos Aires (Argentina)
      between June 2009 and December 2013. The patients were classified into three
      groups according to the severity of hypercholanemia at diagnosis; mild (10-19.9
      MUmol/L), moderate (20-39.9 MUmol/L) and severe (>=40 MUmol/L). Their clinical
      characteristics and pregnancy outcomes were investigated in a prospective
      observational study. RESULTS: Higher risk of MSAF was observed when ICP appeared
      early in gestation or when hypercholanemia was more severe. Taking both
      parameters into account an MSAF risk factor (MRF) was defined. Based on a model
      of positive/negative predictive values, a cut-off point of MRF = 3 was selected,
      which prioritized sensitivity versus specificity. In ICP patients with MRF>3, the
      probability of MSAF was enhanced 4-fold. An increase in the frequency of MSAF was
      also associated with higher serum levels at diagnosis of alanine transaminase,
      alkaline phosphatase and direct bilirubin. CONCLUSIONS: The risk of MSAF is
      associated not only with the magnitude of hypercholanemia at diagnosis but also
      with the early gestational onset of raised maternal serum bile acids.

PMID- 28437443
TI  - Relative predictive value of lung cancer screening CT versus myocardial perfusion
      attenuation correction CT in the evaluation of coronary calcium.
AB  - Coronary artery calcium scores (CACS) from lung cancer screening computed
      tomography (LCSCT) or myocardial perfusion attenuation correction computed
      tomography (ACCT) are not routinely performed or reported. CACS from LCSCT and
      ACCT have not been directly compared in the same patient population. We
      identified 66 patients who underwent both LCSCT (non-gated) and ECG-gated cardiac
      CT (CCT) within a 2-year span. Of this population, 40 subjects had also undergone
      ACCT. Using the Agatston method, CACS for 264 individual vessels from the LCSCT
      population and for 160 vessels from ACCT population were calculated and evaluated
      for agreement with ECG-gated CCT as the gold standard. Secondary analysis
      included a comparison of individual vessel contribution to variations in
      agreement and a comparison of total CACS from CCT, LCSCT, and ACCT for respective
      MACE prediction. CACS from LCSCT demonstrated a strong Pearson correlation, r =
      0.9017 (0.876-0.9223), with good agreement when compared to CACS from CCT. CACS
      from ACCT demonstrated a significantly (P < 0.00001) weaker correlation, r =
      0.5593 (0.4401-0.6592). On an individual vessel basis, CACS from all major
      vessels (LM, LAD, LCX, and RCA) contributed to the weaker correlation. For total
      vessel CACS, LCSCT demonstrated comparable area under the curve (AUC) for the
      receiver operating characteristic (ROC) curve (LCSCT AUC = 0.8133 and CCT AUC =
      0.8302, P = 0.691) for prediction of MACE. Although ACCT demonstrated a similar
      AUC (ACCT AUC = 0.7969, P = 0.662) for MACE prediction the cutoff value for
      elevated risk was extremely low. In conclusion, LCSCT outperformed ACCT at
      calcium scoring by providing better agreement and comparable risk assessment to
      CCT despite the absence of ECG-gating. It is therefore reasonable to use LCSCT
      images to derive and report Agatston-based CACS for cardiovascular risk
      assessment, whereas the use of ACCT images to report Agatston-based CACS is not
      currently practical.

PMID- 28437444
TI  - Transcriptional bursting in Drosophila development: Stochastic dynamics of eve
      stripe 2 expression.
AB  - Anterior-posterior (AP) body segmentation of the fruit fly (Drosophila) is first
      seen in the 7-stripe spatial expression patterns of the pair-rule genes, which
      regulate downstream genes determining specific segment identities. Regulation of
      pair-rule expression has been extensively studied for the even-skipped (eve)
      gene. Recent live imaging, of a reporter for the 2nd eve stripe, has demonstrated
      the stochastic nature of this process, with 'bursts' in the number of RNA
      transcripts being made over time. We developed a stochastic model of the spatial
      and temporal expression of eve stripe 2 (binding by transcriptional activators
      (Bicoid and Hunchback proteins) and repressors (Giant and Kruppel proteins),
      transcriptional initiation and termination; with all rate parameters constrained
      by features of the experimental data) in order to analyze the noisy experimental
      time series and test hypotheses for how eve transcription is regulated. These
      include whether eve transcription is simply OFF or ON, with a single ON rate, or
      whether it proceeds by a more complex mechanism, with multiple ON rates. We find
      that both mechanisms can produce long (multi-minute) RNA bursts, but that the
      short-time (minute-to-minute) statistics of the data is indicative of eve being
      transcribed with at least two distinct ON rates, consistent with data on the
      joint activation of eve by Bicoid and Hunchback. We also predict distinct
      statistical signatures for cases in which eve is repressed (e.g. along the edges
      of the stripe) vs. cases in which activation is reduced (e.g. by mutagenesis of
      transcription factor binding sites). Fundamental developmental processes such as
      gene transcription are intrinsically noisy; our approach presents a new way to
      quantify and analyze time series data during developmental patterning in order to
      understand regulatory mechanisms and how they propagate noise and impact
      embryonic robustness.

PMID- 28437445
TI  - Knowledge and perception of cardiovascular disease risk among patients with
      rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis are at increased risk for cardiovascular
      disease. The prerequisites for reducing the risk of cardiovascular disease are
      adequate levels of knowledge and being aware of the risk. In this study, the
      levels of knowledge about cardiovascular disease among patients with rheumatoid
      arthritis and the perception were evaluated in relation to their actual 10-year
      risk of cardiovascular disease. This cross-sectional study of 200 patients with
      rheumatoid arthritis was conducted in a university-affiliated hospital in South
      Korea. The patients' actual risk of cardiovascular disease was estimated using
      the Framingham Risk Score. The most common risk factor was physical inactivity,
      with 77% of the patients not engaging in regular exercise. The patients lacked
      knowledge about the effects of physical inactivity and anti-inflammatory
      medication on the development of cardiovascular disease. Misperceptions about the
      risk of cardiovascular disease were common, i.e., 19.5% of the patients
      underestimated their risk and 41% overestimated. Hypertension, diabetes, obesity,
      and smoking were the most prevalent among the patients who underestimated their
      risk, and these same patients had the lowest level of knowledge about
      cardiovascular disease. This study demonstrated the rheumatoid arthritis
      patients' lack of knowledge about the effects of physical inactivity and anti
      inflammatory medications on the development of cardiovascular disease, and their
      misperception of cardiovascular risk was common. As a preventive measure,
      educational programs about cardiovascular disease should be tailored specifically
      for patients with rheumatoid arthritis, and behavioral interventions, including
      routine exercise, should be made available at the time of diagnosis.

PMID- 28437446
TI  - Solid state characterization and theoretical study of non-linear optical
      properties of a Fluoro-N-Acylhydrazide derivative.
AB  - In this work we determine the linear and non-linear optical properties of a
      Fluoro-N-Acylhydrazide derivative (FBHZ), using a combined supermolecule approach
      and an iterative scheme of electrostatic polarization, where the atoms of
      neighbouring molecules are represented by point charges. Our results for non
      linear optics (NLO) are comparable to those found experimentally, suggesting that
      FBHZ constitutes an attractive object for future studies and for use as an
      interesting material for third-order NLO applications. The dynamic electrical
      properties of FBHZ in different solvent media are reported. Its molecular
      properties are closely related to supramolecular features; accordingly, we
      analysed all its crystal structure properties via intermolecular interactions in
      the solid state, using X-ray crystallography data and Hirshfeld surface (HS),
      including thermogravimetric analysis (TGA), differential scanning calorimetry
      (DSC) and hot-stage microscopy (HSM), where the results reveal crystal stability
      in respect to temperature variation.

PMID- 28437447
TI  - Carbonic anhydrase III (Car3) is not required for fatty acid synthesis and does
      not protect against high-fat diet induced obesity in mice.
AB  - Carbonic anhydrases are a family of enzymes that catalyze the reversible
      condensation of water and carbon dioxide to carbonic acid, which spontaneously
      dissociates to bicarbonate. Carbonic anhydrase III (Car3) is nutritionally
      regulated at both the mRNA and protein level. It is highly enriched in tissues
      that synthesize and/or store fat: liver, white adipose tissue, brown adipose
      tissue, and skeletal muscle. Previous characterization of Car3 knockout mice
      focused on mice fed standard diets, not high-fat diets that significantly alter
      the tissues that highly express Car3. We observed lower protein levels of Car3 in
      high-fat diet fed mice treated with niclosamide, a drug published to improve
      fatty liver symptoms in mice. However, it is unknown if Car3 is simply a
      biomarker reflecting lipid accumulation or whether it has a functional role in
      regulating lipid metabolism. We focused our in vitro studies toward metabolic
      pathways that require bicarbonate. To further determine the role of Car3 in
      metabolism, we measured de novo fatty acid synthesis with in vitro radiolabeled
      experiments and examined metabolic biomarkers in Car3 knockout and wild type mice
      fed high-fat diet. Specifically, we analyzed body weight, body composition,
      metabolic rate, insulin resistance, serum and tissue triglycerides. Our results
      indicate that Car3 is not required for de novo lipogenesis, and Car3 knockout
      mice fed high-fat diet do not have significant differences in responses to
      various diets to wild type mice.

PMID- 28437448
TI  - Expression profiling of Chrysanthemum crassum under salinity stress and the
      initiation of morphological changes.
AB  - Chrysanthemum crassum is a decaploid species of Chrysanthemum with high stress
      tolerance that allows survival under salinity stress while maintaining a
      relatively ideal growth rate. We previously recorded morphological changes after
      salt treatment, such as the expansion of leaf cells. To explore the underlying
      salinity tolerance mechanisms, we used an Illumina platform and obtained three
      sequencing libraries from samples collected after 0 h, 12 h and 24 h of salt
      treatment. Following de novo assembly, 154,944 transcripts were generated, and
      97,833 (63.14%) transcripts were annotated, including 55 Gene Ontology (GO) terms
      and 128 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The expression
      profile of C. crassum was globally altered after salt treatment. We selected
      functional genes and pathways that may contribute to salinity tolerance and
      identified some factors involved in the salinity tolerance strategies of C.
      crassum, such as signal transduction, transcription factors and plant hormone
      regulation, enhancement of energy metabolism, functional proteins and osmolyte
      synthesis, reactive oxygen species (ROS) scavenging, photosystem protection and
      recovery, and cell wall protein modifications. Forty-six genes were selected for
      quantitative real-time polymerase chain reaction detection, and their expression
      patterns were shown to be consistent with the changes in their transcript
      abundance determined by RNA sequencing.

PMID- 28437449
TI  - Insecticide resistance status of malaria vectors in Lao PDR.
AB  - Knowledge on insecticide resistance in Anopheles species is a basic requirement
      to guide malaria vector control programs. In Lao PDR, vector control relies on
      insecticide residual spraying (IRS) and impregnated bed-nets (ITNs) with the use
      of pyrethroids. Here, the susceptibility of Anopheles species, including several
      malaria vectors (An. maculatus and An. minimus), to various insecticides was
      investigated in ten provinces of Lao PDR through a north-south transect.
      Bioassays were performed on field caught female mosquitoes using the standard WHO
      susceptibility tests with DDT (4%), deltamethrin (0.05%) and permethrin (0.75%).
      In addition, the DIIS6 region of the para-type sodium channel gene was amplified
      and sequenced to identify knockdown resistance mutations (kdr). Resistance to DDT
      and permethrin was detected in suspected malaria vectors, such as An. nivipes and
      An. philippinensis in Lao PDR. Resistance to the formerly used DDT was found in a
      population of An. maculatus s.l. from Luang Prabang province. No resistance to
      pyrethroids was found in primary vectors, indicating that these insecticides are
      still adequate for malaria vector control. However, high resistance levels to
      pyrethroids was found in-vector species and reduced susceptibility to permethrin
      in An. minimus and An. maculatus was reported in specific localities which raises
      concerns for pyrethroid-based control in the future. No kdr mutation was found in
      any of the resistant populations tested hence suggesting a probable role
      detoxification enzymes in resistance. This study highlights the necessity to
      continue the monitoring of insecticide susceptibility to early detect potential
      occurrence and/or migration of insecticide resistance in malaria vectors in Lao
      PDR.

PMID- 28437450
TI  - ESPRIT-Forest: Parallel clustering of massive amplicon sequence data in
      subquadratic time.
AB  - The rapid development of sequencing technology has led to an explosive
      accumulation of genomic sequence data. Clustering is often the first step to
      perform in sequence analysis, and hierarchical clustering is one of the most
      commonly used approaches for this purpose. However, it is currently
      computationally expensive to perform hierarchical clustering of extremely large
      sequence datasets due to its quadratic time and space complexities. In this paper
      we developed a new algorithm called ESPRIT-Forest for parallel hierarchical
      clustering of sequences. The algorithm achieves subquadratic time and space
      complexity and maintains a high clustering accuracy comparable to the standard
      method. The basic idea is to organize sequences into a pseudo-metric based
      partitioning tree for sub-linear time searching of nearest neighbors, and then
      use a new multiple-pair merging criterion to construct clusters in parallel using
      multiple threads. The new algorithm was tested on the human microbiome project
      (HMP) dataset, currently one of the largest published microbial 16S rRNA sequence
      dataset. Our experiment demonstrated that with the power of parallel computing it
      is now compu- tationally feasible to perform hierarchical clustering analysis of
      tens of millions of sequences. The software is available at
      http://www.acsu.buffalo.edu/~yijunsun/lab/ESPRIT-Forest.html.

PMID- 28437451
TI  - Predicting explorative motor learning using decision-making and motor noise.
AB  - A fundamental problem faced by humans is learning to select motor actions based
      on noisy sensory information and incomplete knowledge of the world. Recently, a
      number of authors have asked whether this type of motor learning problem might be
      very similar to a range of higher-level decision-making problems. If so,
      participant behaviour on a high-level decision-making task could be predictive of
      their performance during a motor learning task. To investigate this question, we
      studied performance during an explorative motor learning task and a decision
      making task which had a similar underlying structure with the exception that it
      was not subject to motor (execution) noise. We also collected an independent
      measurement of each participant's level of motor noise. Our analysis showed that
      explorative motor learning and decision-making could be modelled as the
      (approximately) optimal solution to a Partially Observable Markov Decision
      Process bounded by noisy neural information processing. The model was able to
      predict participant performance in motor learning by using parameters estimated
      from the decision-making task and the separate motor noise measurement. This
      suggests that explorative motor learning can be formalised as a sequential
      decision-making process that is adjusted for motor noise, and raises interesting
      questions regarding the neural origin of explorative motor learning.

PMID- 28437452
TI  - Enhanced antibacterial metabolite production through the application of
      statistical methodologies by a Streptomyces nogalater NIIST A30 isolated from
      Western Ghats forest soil.
AB  - Streptomyces strains isolated from Nelliyampathy forest soil of Western Ghats,
      Kerala, India were evaluated for their antibacterial efficacy against two
      indicator pathogenic bacteria (Escherichia coli and Staphylococcus aureus). Among
      140 strains tested, sixteen recorded potent antibacterial properties and were
      further screened against eleven bacterial pathogens. A strain identified as
      Streptomyces nogalater and designated as NIIST A30 exhibited maximum inhibition
      against all the test pathogens. Among the eight fermentation media tested,
      inorganic salts starch broth recorded the best for antibacterial production. The
      ethyl acetate crude extract exhibited antioxidant properties with IC50 value of
      30 MUg/mL and had no cytotoxicity towards L6, H9c2 and RAW 264.7 cell lines up to
      a concentration of 50 MUg/mL. Maximum metabolite production was achieved in pH
      7.0 at 35 degrees C after 7 days incubation. The significant media components for
      maximum metabolite production were optimized through response surface methodology
      employing Plackett-Burman and Box-Behnken designs. The composition of the final
      optimized medium was soluble starch, 14.97g; (NH4)2SO4, 2.89g; K2HPO4, 2.07g;
      MgSO4.7H2O, 1g; NaCl, 1g, CaCO3, 2g; FeSO4.7H2O, 1mg; MnCl2.7H2O, 1mg; and
      ZnSO4.7H2O, 1mg per litre of distilled water. The optimization resulted an
      antibacterial activity of 28+/-1.5mm against S. epidermidis which was in close
      accordance with the predicted value of 30 mm. It is also evident from the result
      that an increase of 86.66% antibacterial production was recorded in optimized
      media. The chosen method was economical, efficient and useful for future
      antibacterial drug discovery from a broad spectrum metabolite producer like
      Streptomyces nogalater NIIST A30.

PMID- 28437453
TI  - Three dominant awnless genes in common wheat: Fine mapping, interaction and
      contribution to diversity in awn shape and length.
AB  - The awn is a long needle-like structure formed at the tip of the lemma in the
      florets of some grass species. It plays a role in seed dispersal and protection
      against animals, and can contribute to the photosynthetic activity of spikes.
      Three main dominant inhibitors of awn development (Hd, B1 and B2) are known in
      hexaploid wheat, but the causal genes have not been cloned yet and a genetic
      association with awn length diversity has been found only for the B1 allele. To
      analyze the prevalence of these three awning inhibitors, we attempted to predict
      the genotypes of 189 hexaploid wheat varieties collected worldwide using markers
      tightly linked to these loci. Using recombinant inbred lines derived from two
      common wheat cultivars, Chinese Spring and Mironovskaya 808, both with short
      awns, and a high-density linkage map, we performed quantitative trait locus
      analysis to identify tightly linked markers. Because this linkage map was
      constructed with abundant array-based markers, we converted the linked markers to
      PCR-based markers and determined the genotypes of 189 hexaploids. A significant
      genotype-phenotype correlation was observed at the Hd and B1 regions. We also
      found that interaction among these three awning inhibitors is involved in
      development of a membranous outgrowth at the base of awn resembling the Hooded
      mutants of barley. For the hooded awn phenotype, presence of the Hd dominant
      allele was essential but not sufficient, so B2 and other factors appear to act
      epistatically to produce the ectopic tissue. On the other hand, the dominant B1
      allele acted as a suppressor of the hooded phenotype. These three awning
      inhibitors largely contribute to the genetic variation in awn length and shape of
      common wheat.

PMID- 28437454
TI  - Age-associated increase of the active zone protein Bruchpilot within the honeybee
      mushroom body.
AB  - In honeybees, age-associated structural modifications can be observed in the
      mushroom bodies. Prominent examples are the synaptic complexes (microglomeruli,
      MG) in the mushroom body calyces, which were shown to alter their size and
      density with age. It is not known whether the amount of intracellular synaptic
      proteins in the MG is altered as well. The presynaptic protein Bruchpilot (BRP)
      is localized at active zones and is involved in regulating the probability of
      neurotransmitter release in the fruit fly, Drosophila melanogaster. Here, we
      explored the localization of the honeybee BRP (Apis mellifera BRP, AmBRP) in the
      bee brain and examined age-related changes in the AmBRP abundance in the central
      bee brain and in microglomeruli of the mushroom body calyces. We report
      predominant AmBRP localization near the membrane of presynaptic boutons within
      the mushroom body MG. The relative amount of AmBRP was increased in the central
      brain of two-week old bees whereas the amount of Synapsin, another presynaptic
      protein involved in the regulation of neurotransmitter release, shows an increase
      during the first two weeks followed by a decrease. In addition, we demonstrate an
      age-associated modulation of AmBRP located near the membrane of presynaptic
      boutons within MG located in mushroom body calyces where sensory input is
      conveyed to mushroom body intrinsic neurons. We discuss that the observed age
      associated AmBRP modulation might be related to maturation processes or to
      homeostatic mechanisms that might help to maintain synaptic functionality in old
      animals.

PMID- 28437456
TI  - Correction: Modeling the potential impact on the US blood supply of transfusing
      critically ill patients with fresher stored red blood cells.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0174033.].

PMID- 28437455
TI  - Effect of a probiotic beverage consumption (Enterococcus faecium CRL 183 and
      Bifidobacterium longum ATCC 15707) in rats with chemically induced colitis.
AB  - BACKGROUND: Some probiotic strains have the potential to assist in relieving the
      symptoms of inflammatory bowel disease. The impact of daily ingestion of a soy
      based product fermented by Enterococcus faecium CRL 183 and Lactobacillus
      helveticus 416 with the addition of Bifidobacterium longum ATCC 15707 on
      chemically induced colitis has been investigated thereof within a period of 30
      days. METHODS: Colitis was induced by dextran sulfate sodium. The animals were
      randomly assigned into five groups: Group C: negative control; Group CL: positive
      control; Group CLF: DSS with the fermented product; Group CLP: DSS with the non
      fermented product (placebo); Group CLS: DSS with sulfasalazine. The following
      parameters were monitored: disease activity index, fecal microbial analyses,
      gastrointestinal survival of probiotic microorganisms and short-chain fatty acids
      concentration in the feces. At the end of the protocol the animals' colons were
      removed so as to conduct a macroscopical and histopathological analysis,
      cytokines and nitrite quantification. RESULTS: Animals belonging to the CLF group
      showed fewer symptoms of colitis during the induction period and a lower degree
      of inflammation and ulceration in their colon compared to the CL, CLS and CLP
      groups (p<0.05). The colon of the animals in groups CL and CLS presented severe
      crypt damage, which was absent in CLF and CLP groups. A significant increase in
      the population of Lactobacillus spp. and Bifidobacterium spp. at the end of the
      protocol was verified only in the CLF animals (p<0.05). This group also showed an
      increase in short-chain fatty acids (propionate and acetate). Furthermore, the
      intestinal survival of E. faecium CRL 183 and B. longum ATCC 15707 in the CLF
      group has been confirmed by biochemical and molecular analyzes. CONCLUSIONS: The
      obtained results suggest that a regular intake of the probiotic product, and
      placebo to a lesser extent, can reduce the severity of DSS-induced colitis on
      rats.

PMID- 28437457
TI  - Tissue factor-dependent coagulation activation by heme: A thromboelastometry
      study.
AB  - Heme has been characterized as potent trigger of inflammation. In hemostasis,
      although heme has been shown to both induce and inhibit different compartments of
      hemostasis, its net effect on the hemostatic balance, and the biological
      relevance of these effects remain to be determined. Herein we evaluated the
      effect of heme on hemostasis using a global assay able to generate clinically
      relevant data in several other complex hemostatic diseases. Citrated whole blood
      samples from healthy participants were stimulated by heme or vehicle and
      incubated for 4h at 37 degrees C. Rotational thromboelastometry was immediately
      performed. The participation of tissue factor in coagulation activation was
      evaluated using inhibitory antibody. Heme was able of inducing ex vivo
      coagulation activation in whole blood, affecting predominantly parameters
      associated with the initial phases of clot formation. This activation effect was
      at least partially dependent on hematopoietic tissue factor, since the effects of
      heme were partially abrogated by the inhibition of human tissue factor. In
      conclusion, using a global hemostasis assay, our study confirmed that heme is
      able to activate coagulation in whole blood, in a tissue factor-dependent way.
      These findings could explain the disturbance in hemostatic balance observed in
      conditions associated with the release of heme such as sickle cell disease.

PMID- 28437458
TI  - Isomalto-oligosaccharides ameliorate visceral hyperalgesia with repair damage of
      ileal epithelial ultrastructure in rats.
AB  - BACKGROUND: Treatment of irritable bowel syndrome (IBS) with probiotics has
      achieved effectiveness to a certain extent. Whether prebiotics will work is still
      unclear. This study aimed to investigate the therapeutic effects of the prebiotic
      isomalto-oligosaccharides (IMO) on visceral hypersensitivity (VHS) in rats and to
      explore potential mechanism. METHODS: Water avoidance stress (WAS) was used to
      induce VHS in rats. The score for the abdominal withdrawal reflex (AWR) was
      determined while colorectal distension and compared between VHS group and control
      group in order to validate VHS preparation. Rats with VHS were then divided into
      an IMO-treated group (intragastric 5% IMO, 2 mL/d, 14 days) and a water-control
      group (intragastric water). After treatment, AWR score and intestinal transit
      rate (ITR) were determined, stool culture was performed, the ultrastructure of
      the ileum epithelium was observed with scanning electron microscopy (SEM), and
      serum cytokines were measured. RESULTS: WAS significantly increased AWR score
      responding to colorectal distension, and lowered the pain threshold. IMO
      treatment improved VHS with a reduction in AWR score on graded colorectal
      distension and an increase in pain threshold. SEM showed damages on the ileal
      epithelial ultrastructure in VHS rats, which was attenuated by IMO treatment.
      ITR, fecal microbiota and serum cytokine levels were comparable among control
      group, water-control group, and IMO-treated rats. CONCLUSION: In this randomized
      placebo-controlled study, the results showed that IMO ameliorated WAS-induced
      visceral hyperalgesia in rats, this effect may be attributed to the repair of
      damages on intestinal epithelial ultrastructure.

PMID- 28437459
TI  - Management and outcomes of severe dengue patients presenting with sepsis in a
      tropical country.
AB  - BACKGROUND: Dengue is a common cause of infection in adults in tropical
      countries. Sepsis is a syndrome of systemic manifestations induced by infection
      of any organisms; including bacterial, fungal and viral agents. Here, we
      investigated the diagnosis, management and outcomes of dengue patients presenting
      with sepsis in a prospective study of community-acquired sepsis in Thailand.
      METHODS: From June to December 2015, 874 adult patients (age>=18 years) with
      suspected or documented community-acquired infection, with >=3 diagnostic
      criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within
      24 hours of admission were evaluated. Serum was stored and later tested for
      dengue PCR assays. RESULTS: A total of 126 patients had dengue PCR assays
      positive (2 DENV-1, 12 DENV-2, 24 DENV-3 and 88 DENV-4), and 5 of them (4%) died.
      We found that attending physicians suspected dengue infection on admission in 84
      patients (67%), and recorded dengue infection as the final diagnosis in 96
      patients (76%). Four of five fatal cases were diagnosed and treated as septic
      shock not due to dengue. In multivariable analysis, there was a trend showing
      that age>=60 years, hypoxemia and misdiagnosis of dengue by attending physicians
      were associated with 28-day mortality. CONCLUSIONS: A number of adult patients
      who died of dengue are misdiagnosed as severe sepsis and septic shock. Diagnosis
      of dengue based on clinical features alone is difficult. Rapid diagnostic tests
      for dengue may need to be routinely used in adult patients presenting with sepsis
      and septic shock in tropical countries. This approach could improve diagnosis and
      management of those patients.

PMID- 28437460
TI  - An aggregation-removal model for the formation and size determination of post
      synaptic scaffold domains.
AB  - The formation and stability of synapses are key questions in neuroscience. Post
      synaptic domains have been classically conceived as resulting from local
      insertion and turnover of proteins at the synapse. However, insertion is likely
      to occur outside the post-synaptic domains and advances in single-molecule
      imaging have shown that proteins diffuse in the plane of the membrane prior to
      their accumulation at synapses. We quantitatively investigated this scenario
      using computer simulations and mathematical analysis, taking for definiteness the
      specific case of inhibitory synapse components, i.e., the glycine receptor (GlyR)
      and the associated gephyrin scaffolding protein. The observed domain sizes of
      scaffold clusters can be explained by a dynamic balance between the aggregation
      of gephyrin proteins diffusing while bound to GlyR and their turnover at the
      neuron membrane. We also predict the existence of extrasynaptic clusters with a
      characteristic size distribution that significantly contribute to the size
      fluctuations of synaptic domains. New super-resolution data for gephyrin proteins
      established the existence of extrasynaptic clusters the sizes of which are
      consistent with the model predictions in a range of model parameters. At a
      general level, our results highlight aggregation with removal as a non
      equilibrium phase separation which produces structures of tunable size.

PMID- 28437462
TI  - Correction: Virtual Hand Feedback Reduces Reaction Time in an Interactive Finger
      Reaching Task.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0154807.].

PMID- 28437461
TI  - Comparison of risk factors and outcomes of gestational hypertension and pre
      eclampsia.
AB  - BACKGROUND: It remains an enigma whether gestational hypertension (GH) and pre
      eclampsia (PE) are distinct entities or different spectrum of the same disease.
      We aimed to compare the risk factors and outcomes between GH and PE. METHOD: A
      total of 7,633 pregnant women recruited between 12 and 20 weeks of gestation in
      the Ottawa and Kingston Birth Cohort from 2002 to 2009 were included in the
      analysis. Cox proportional hazards model was used to identify and compare the
      risk factors for GH and PE by treating gestational age at delivery as the
      survival time. Logistic regression model was used to compare outcome. Subgroup
      analysis was performed for early- and late-onset PE. RESULTS: GH and PE shared
      most risk factors including overweight and obesity, nulliparity, PE history, type
      1 and 2 diabetes, and twin birth. Effect size of PE history (RR = 14.1 for GH vs.
      RR = 6.4 for PE) and twin birth (RR = 4.8 for GH vs. RR = 10.3 for PE) showed
      substantial difference. Risk factors modified gestational age at delivery in
      patients with GH and PE in similar pattern. Subgroup analysis showed that early-
      and late-onset PE shared some risk factors with different effect sizes, whereas
      folic acid supplementation showed protective effect for early-onset PE only. PE
      was strongly associated with several adverse outcomes including cesarean section,
      placental abruption, small for gestational age, preterm birth, and 5 min Apgar
      score < 7, whereas GH was associated with increased risk of preterm birth only.
      CONCLUSIONS: GH and PE shared common risk factors. Differences in effect sizes of
      risk factors and outcomes indicate that the conditions may have different
      pathophysiology and mechanism.

PMID- 28437463
TI  - Relationship of the CreBC two-component regulatory system and inner membrane
      protein CreD with swimming motility in Stenotrophomonas maltophilia.
AB  - The CreBC two-component system (TCS) is a conserved regulatory system found in
      Escherichia coli, Aeromonas spp., Pseudomonas aeruginosa, and Stenotrophomonas
      maltophilia. In this study, we determined how CreBC TCS regulates secreted
      protease activities and swimming motility using creB, creC, and creBC in-frame
      deletion mutants (KJDeltaCreB, KJDeltaCreC, and KJDeltaBC) of S. maltophilia KJ.
      Compared to wild-type KJ, KJDeltaCreB had a comparable secreted protease
      activity; however, the secreted protease activities were obviously reduced in
      KJDeltaCreC and KJDeltaBC, suggesting that CreC works together with another
      unidentified response regulator (not CreB) to regulate secreted protease
      activity. Single gene inactivation of creB or creC resulted in mutants with an
      enhanced swimming motility, and this phenotype was exacerbated in a double mutant
      KJDeltaBC. To elucidate the underlying mechanism responsible for the DeltacreBC
      mediated swimming enhancement, flagella morphology observation, RNA-seq based
      transcriptome assay, qRT-PCR, and membrane integrity and potential assessment
      were performed. Flagella morphological observation ruled out the possibility that
      swimming enhancement was due to altered flagella morphology. CreBC inactivation
      upregulated the expression of creD and flagella-associated genes encoding the
      basal body- and motor-associated proteins. Furthermore, KJDeltaBC had an
      increased membrane susceptibility to Triton X-100 and CreD upregulation in
      KJDeltaBC partially alleviated the compromise of membrane integrity. The impact
      of creBC TCS on bacterial membrane potential was assessed by carbonyl cyanide m
      chlorophenyl hydrazine (CCCP50) concentration at which 50% of bacterial swimming
      is inhibited. CCCP50 of wild-type KJ increased when creBC was deleted, indicating
      an association between the higher membrane potential of KJDeltaBC cells and
      enhanced motility. Upregulation of the basal body- and motor-associated genes of
      flagella in KJDeltaBC cells may explain the increased membrane potential.
      Collectively, inactivation of creBC increased swimming motility through membrane
      potential increase and creD upregulation in S. maltophilia. The increased
      membrane potential may supply more energy for flagella propelling and CreD
      upregulation supports membrane stability, providing a strong membrane for
      flagellum function.

PMID- 28437464
TI  - Inhibition of alphavbeta3 integrin induces loss of cell directionality of oral
      squamous carcinoma cells (OSCC).
AB  - The connective tissue formed by extracellular matrix (ECM) rich in fibronectin
      and collagen consists a barrier that cancer cells have to overpass to reach blood
      vessels and then a metastatic site. Cell adhesion to fibronectin is mediated by
      alphavbeta3 and alpha5beta1 integrins through an RGD motif present in this ECM
      protein, thus making these receptors key targets for cell migration studies. Here
      we investigated the effect of an RGD disintegrin, DisBa-01, on the migration of
      human fibroblasts (BJ) and oral squamous cancer cells (OSCC, SCC25) on a
      fibronectin-rich environment. Time-lapse images were acquired on fibronectin
      coated glass-bottomed dishes. Migration speed and directionality analysis
      indicated that OSCC cells, but not fibroblasts, showed significant decrease in
      both parameters in the presence of DisBa-01 (1MUM and 2MUM). Integrin expression
      levels of the alpha5, alphav and beta3 subunits were similar in both cell lines,
      while beta1 subunit is present in lower levels on the cancer cells. Next, we
      examined whether the effects of DisBa-01 were related to changes in adhesion
      properties by using paxillin immunostaining and total internal reflection
      fluorescence TIRF microscopy. OSCCs in the presence of DisBa-01 showed increased
      adhesion sizes and number of maturing adhesion. The same parameters were analyzed
      usingbeta3-GFP overexpressing cells and showed that beta3 overexpression restored
      cell migration velocity and the number of maturing adhesion that were altered by
      DisBa-01. Surface plasmon resonance analysis showed that DisBa-01 has 100x higher
      affinity for alphavbeta3 integrin than foralpha5beta1 integrin. In conclusion,
      our results suggest that the alphavbeta3 integrin is the main receptor involved
      in cell directionality and its blockage may be an interesting alternative against
      metastasis.

PMID- 28437465
TI  - Serological evidence for transmission of multiple dengue virus serotypes in Papua
      New Guinea and West Papua prior to 1963.
AB  - Little is known about the natural history of dengue in Papua New Guinea (PNG). We
      assessed dengue virus (DENV)-specific neutralizing antibody profiles in serum
      samples collected from northern and southern coastal areas and the highland
      region of New Guinea between 1959 and 1963. Neutralizing antibodies were
      demonstrated in sera from the northern coast of New Guinea: from Sabron in Dutch
      New Guinea (now known as West Papua) and from four villages in East Sepik in what
      is now PNG. Previous monotypic infection with DENV-1, DENV-2, and DENV-4 was
      identified, with a predominance of anti-DENV-2 neutralizing antibody. The
      majority of positive sera demonstrated evidence of multiple previous DENV
      infections and neutralizing activity against all four serotypes was detected,
      with anti-DENV-2 responses being most frequent and of greatest magnitude. No
      evidence of previous DENV infection was identified in the Asmat villages of the
      southern coast and a single anti-DENV-positive sample was identified in the
      Eastern Highlands of PNG. These findings indicate that multiple DENV serotypes
      circulated along the northern coast of New Guinea at different times in the
      decades prior to 1963 and support the notion that dengue has been a significant
      yet neglected tropical infection in PNG for many decades.

PMID- 28437466
TI  - Stage call: Cardiovascular reactivity to audition stress in musicians.
AB  - Auditioning is at the very center of educational and professional life in music
      and is associated with significant psychophysical demands. Knowledge of how these
      demands affect cardiovascular responses to psychosocial pressure is essential for
      developing strategies to both manage stress and understand optimal performance
      states. To this end, we recorded the electrocardiograms (ECGs) of 16 musicians
      (11 violinists and 5 flutists) before and during performances in both low- and
      high-stress conditions: with no audience and in front of an audition panel,
      respectively. The analysis consisted of the detection of R-peaks in the ECGs to
      extract heart rate variability (HRV) from the notoriously noisy real-world ECGs.
      Our data analysis approach spanned both standard (temporal and spectral) and
      advanced (structural complexity) techniques. The complexity science approaches
      namely, multiscale sample entropy and multiscale fuzzy entropy-indicated a
      statistically significant decrease in structural complexity in HRV from the low-
      to the high-stress condition and an increase in structural complexity from the
      pre-performance to performance period, thus confirming the complexity loss theory
      and a loss in degrees of freedom due to stress. Results from the spectral
      analyses also suggest that the stress responses in the female participants were
      more parasympathetically driven than those of the male participants. In
      conclusion, our findings suggest that interventions to manage stress are best
      targeted at the sensitive pre-performance period, before an audition begins.

PMID- 28437467
TI  - Mutant uromodulin expression leads to altered homeostasis of the endoplasmic
      reticulum and activates the unfolded protein response.
AB  - Uromodulin is the most abundant urinary protein in physiological conditions. It
      is exclusively produced by renal epithelial cells lining the thick ascending limb
      of Henle's loop (TAL) and it plays key roles in kidney function and disease.
      Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant
      tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD), characterised
      by hyperuricemia, gout and progressive loss of renal function. While the primary
      effect of UMOD mutations, retention in the endoplasmic reticulum (ER), is well
      established, its downstream effects are still largely unknown. To gain insight
      into ADTKD-UMOD pathogenesis, we performed transcriptional profiling and
      biochemical characterisation of cellular models (immortalised mouse TAL cells) of
      robust expression of wild type or mutant GFP-tagged uromodulin. In this model
      mutant uromodulin accumulation in the ER does not impact on cell viability and
      proliferation. Transcriptional profiling identified 109 genes that are
      differentially expressed in mutant cells relative to wild type ones. Up-regulated
      genes include several ER resident chaperones and protein disulphide isomerases.
      Consistently, pathway enrichment analysis indicates that mutant uromodulin
      expression affects ER function and protein homeostasis. Interestingly, mutant
      uromodulin expression induces the Unfolded Protein Response (UPR), and
      specifically the IRE1 branch, as shown by an increased splicing of XBP1.
      Consistent with UPR induction, we show increased interaction of mutant uromodulin
      with ER chaperones Bip, calnexin and PDI. Using metabolic labelling, we also
      demonstrate that while autophagy plays no role, mutant protein is partially
      degraded by the proteasome through ER-associated degradation. Our work
      demonstrates that ER stress could play a central role in ADTKD-UMOD pathogenesis.
      This sets the bases for future work to develop novel therapeutic strategies
      through modulation of ER homeostasis and associated protein degradation pathways.

PMID- 28437468
TI  - Role of cleavage at the core-E1 junction of hepatitis C virus polyprotein in
      viral morphogenesis.
AB  - In hepatitis C virus (HCV) polyprotein sequence, core protein terminates with E1
      envelope signal peptide. Cleavage by signal peptidase (SP) separates E1 from the
      complete form of core protein, anchored in the endoplasmic reticulum (ER)
      membrane by the signal peptide. Subsequent cleavage of the signal peptide by
      signal-peptide peptidase (SPP) releases the mature form of core protein, which
      preferentially relocates to lipid droplets. Both of these cleavages are required
      for the HCV infectious cycle, supporting the idea that HCV assembly begins at the
      surface of lipid droplets, yet SPP-catalyzed cleavage is dispensable for
      initiation of budding in the ER. Here we have addressed at what step(s) of the
      HCV infectious cycle SP-catalyzed cleavage at the core-E1 junction is required.
      Taking advantage of the sole system that has allowed visualization of HCV budding
      events in the ER lumen of mammalian cells, we showed that, unexpectedly,
      mutations abolishing this cleavage did not prevent but instead tended to promote
      the initiation of viral budding. Moreover, even though no viral particles were
      released from Huh-7 cells transfected with a full-length HCV genome bearing these
      mutations, intracellular viral particles containing core protein protected by a
      membrane envelope were formed. These were visualized by electron microscopy as
      capsid-containing particles with a diameter of about 70 nm and 40 nm before and
      after delipidation, respectively, comparable to intracellular wild-type particle
      precursors except that they were non-infectious. Thus, our results show that SP
      catalyzed cleavage is dispensable for HCV budding per se, but is required for the
      viral particles to acquire their infectivity and secretion. These data support
      the idea that HCV assembly occurs in concert with budding at the ER membrane.
      Furthermore, capsid-containing particles did not accumulate in the absence of SP
      catalyzed cleavage, suggesting the quality of newly formed viral particles is
      controlled before secretion.

PMID- 28437469
TI  - Virtual race transformation reverses racial in-group bias.
AB  - People generally show greater preference for members of their own racial group
      compared to racial out-group members. This type of 'in-group bias' is evident in
      mimicry behaviors. We tend to automatically mimic the behaviors of in-group
      members, and this behavior is associated with interpersonal sensitivity and
      empathy. However, mimicry is reduced when interacting with out-group members.
      Although race is considered an unchangeable trait, it is possible using
      embodiment in immersive virtual reality to engender the illusion in people of
      having a body of a different race. Previous research has used this technique to
      show that after a short period of embodiment of White people in a Black virtual
      body their implicit racial bias against Black people diminishes. Here we show
      that this technique powerfully enhances mimicry. We carried out an experiment
      with 32 White (Caucasian) female participants. Half were embodied in a White
      virtual body and the remainder in a Black virtual body. Each interacted in two
      different sessions with a White and a Black virtual character, in counterbalanced
      order. The results show that dyads with the same virtual body skin color
      expressed greater mimicry than those of different color. Importantly, this effect
      occurred depending on the virtual body's race, not participants' actual racial
      group. When embodied in a Black virtual body, White participants treat Black as
      their novel in-group and Whites become their novel out-group. This reversed in
      group bias effect was obtained regardless of participants' level of implicit
      racial bias. We discuss the theoretical and practical implications of this
      surprising psychological phenomenon.

PMID- 28437470
TI  - Respiratory syncytial virus-neutralizing serum antibody titers in infants
      following palivizumab prophylaxis with an abbreviated dosing regimen.
AB  - BACKGROUND: Monthly injections of palivizumab during the respiratory syncytial
      virus (RSV) season in at-risk infants reduces RSV-associated hospitalizations.
      However, the additive effect of naturally acquired immunity remains unclear. The
      objective of this study was to assess total neutralizing serum antibodies (NAb)
      against RSV in at-risk infants who had received an abbreviated course of
      palivizumab prophylaxis. METHODS: Serum samples were collected from infants
      enrolled in the RSV Immunoprophylaxis Program in British Columbia, Canada over 2
      consecutive RSV seasons (2013 to 2015). Infants in this program had received an
      abbreviated course of palivizumab in accordance with the provincial guidelines.
      Data were compared to adults and infants less than 12 months of age who did not
      receive palivizumab. Anti-RSV NAb titers were measured using an RSV
      microneutralization assay. FINDINGS: Infants who received palivizumab had anti
      RSV NAb titers at the end of the RSV season that persisted beyond what is
      expected from the pharmacokinetics of palivizumab alone. Moreover, 54% of the
      control infants who did not receive palivizumab and all tested adults had
      protective anti-RSV NAb titers. CONCLUSIONS: Based on our observations, we
      hypothesize that naturally acquired NAb provide additive protection, which may
      significantly reduce the need for additional doses of palivizumab in infants at
      risk of severe RSV infections.

PMID- 28437471
TI  - miR-217 inhibits triple-negative breast cancer cell growth, migration, and
      invasion through targeting KLF5.
AB  - Triple negative breast cancer (TNBC) is one of the most aggressive breast cancers
      without effective targeted therapies. Numerous studies have implied that KLF5
      plays an important roles in TNBC. How is KLF5 regulated by microRNAs has not been
      well studied. Here, we demonstrated that miR-217 down-regulates the expression of
      KLF5 and KLF5's downstream target gene FGF-BP and Cyclin D1 in TNBC cell lines
      HCC1806 and HCC1937. Consequently, miR-217 suppresses TNBC cell growth,
      migration, and invasion. MiR-217 suppresses TNBC, at least partially, through
      down-regulating the KLF5 expression. These results suggest that the miR-217-KLF5
      axis might serve as a potential target for treatment of TNBC.

PMID- 28437472
TI  - Socioeconomic status and type 2 diabetes complications among young adult patients
      in Japan.
AB  - OBJECTIVE: To assess the relationship between socioeconomic status (SES) and
      complications of type 2 diabetes among young adults in Japan. DESIGN: A cross
      sectional study. SETTING: Outpatient wards of 96 member hospitals and clinics of
      the Japan Federation of Democratic Medical Institutions. PARTICIPANTS: A total of
      782 outpatients with type 2 diabetes (525 males, 257 females), aged 20-40 years
      as of March 31, 2012. After excluding 110 participants whose retinopathy
      diagnosis was in question, 672 participants were analyzed. MEASUREMENTS: We
      examined the relations between SES (educational level, income, type of public
      healthcare insurance, and employment status) and diabetes complications
      (retinopathy and nephropathy) using a multivariate logistic regression analysis.
      RESULTS: The prevalence of type 2 diabetic retinopathy was 23.2%, while that of
      nephropathy was 8.9%. The odds of having retinopathy were higher among junior
      high school graduates (OR 1.91, 95% CI 1.09-3.34), patients receiving public
      assistance (OR 2.19, 95% CI 1.20-3.95), and patients with irregular (OR 1.72, 95%
      CI 1.03-2.86) or no employment (OR 2.23, 95% CI 1.36-3.68), compared to those
      with a higher SES, even after covariate adjustment (e.g., age, gender, body mass
      index). Similarly, the odds of having nephropathy were higher among patients with
      middle (OR 3.61, 95% CI 1.69-8.27) or low income levels (OR 2.53, 95% CI 1.11
      6.07), even after covariate adjustment. CONCLUSIONS: Low SES was associated with
      a greater likelihood of type 2 diabetes complications in young adults. These
      findings suggest the necessity of health policies that mitigate socioeconomic
      disparity and thereby reduce the prevalence of diabetic complications.

PMID- 28437473
TI  - Molecular simulations and Markov state modeling reveal the structural diversity
      and dynamics of a theophylline-binding RNA aptamer in its unbound state.
AB  - RNA aptamers are oligonucleotides that bind with high specificity and affinity to
      target ligands. In the absence of bound ligand, secondary structures of RNA
      aptamers are generally stable, but single-stranded and loop regions, including
      ligand binding sites, lack defined structures and exist as ensembles of
      conformations. For example, the well-characterized theophylline-binding aptamer
      forms a highly stable binding site when bound to theophylline, but the binding
      site is unstable and disordered when theophylline is absent. Experimental methods
      have not revealed at atomic resolution the conformations that the theophylline
      aptamer explores in its unbound state. Consequently, in the present study we
      applied 21 microseconds of molecular dynamics simulations to structurally
      characterize the ensemble of conformations that the aptamer adopts in the absence
      of theophylline. Moreover, we apply Markov state modeling to predict the kinetics
      of transitions between unbound conformational states. Our simulation results
      agree with experimental observations that the theophylline binding site is found
      in many distinct binding-incompetent states and show that these states lack a
      binding pocket that can accommodate theophylline. The binding-incompetent states
      interconvert with binding-competent states through structural rearrangement of
      the binding site on the nanosecond to microsecond timescale. Moreover, we have
      simulated the complete theophylline binding pathway. Our binding simulations
      supplement prior experimental observations of slow theophylline binding kinetics
      by showing that the binding site must undergo a large conformational
      rearrangement after the aptamer and theophylline form an initial complex, most
      notably, a major rearrangement of the C27 base from a buried to solvent-exposed
      orientation. Theophylline appears to bind by a combination of conformational
      selection and induced fit mechanisms. Finally, our modeling indicates that when
      Mg2+ ions are present the population of binding-competent aptamer states
      increases more than twofold. This population change, rather than direct
      interactions between Mg2+ and theophylline, accounts for altered theophylline
      binding kinetics.

PMID- 28437474
TI  - Improvement of a tissue maceration technique for the determination of placental
      involvement in schistosomiasis.
AB  - Schistosomiasis in pregnancy may cause low birth weight, prematurity and
      stillbirth of the offspring. The placenta of pregnant women might be involved
      when schistosome ova are trapped in placental tissue. Standard histopathological
      methods only allow the examination of a limited amount of placental tissue and
      are therefore not sufficiently sensitive. Thus, placental schistosomiasis remains
      underdiagnosed and its role in contributing to schistosomiasis-associated
      pregnancy outcomes remains unclear. Here we investigated an advanced maceration
      method in order to recover a maximum number of schistosome ova from the placenta.
      We examined the effect of different potassium hydroxide (KOH) concentrations and
      different tissue fixatives with respect to maceration success and egg morphology.
      Placental tissue was kept either in 0.9% saline, 5% formalin or 70% ethanol and
      was macerated together with Schistosoma mansoni infested mouse livers and KOH 4%
      or 10%, respectively. We found that placenta maceration using 4% KOH at 37
      degrees C for 24 h was the most effective method: placental tissue was completely
      digested, egg morphology was well preserved and alkaline concentration was the
      lowest. Ethanol proved to be the best fixative for this method. Here we propose
      an improved maceration technique in terms of sensitivity, safety and required
      skills, which may enable its wider use also in endemic areas. This technique may
      contribute to clarifying the role of placental involvement in pregnant women with
      schistosomiasis.

PMID- 28437475
TI  - The School Malaise Trap Program: Coupling educational outreach with scientific
      discovery.
AB  - The School Malaise Trap Program (SMTP) provides a technologically sophisticated
      and scientifically relevant educational experience that exposes students to the
      diversity of life, enhancing their understanding of biodiversity while promoting
      environmental stewardship. Since 2013, the SMTP has allowed 15,000 students at
      350 primary and secondary schools to explore insect diversity in Canadian
      schoolyards. Students at each school collected hundreds of insects for an
      analysis of DNA sequence variation that enabled their rapid identification to a
      species. Through this hands-on approach, they participated in a learning exercise
      that conveys a real sense of scientific discovery. As well, the students
      contributed valuable data to the largest biodiversity genomics initiative ever
      undertaken: the International Barcode of Life project. To date, the SMTP has
      sequenced over 80,000 insect specimens, which includes representatives of 7,990
      different species, nearly a tenth of the Canadian fauna. Both surprisingly and
      importantly, the collections generated the first DNA barcode records for 1,288
      Canadian species.

PMID- 28437476
TI  - ClC-3 chloride channel mediates the role of parathyroid hormone [1-34] on
      osteogenic differentiation of osteoblasts.
AB  - INTRODUCTION: Different concentrations of parathyroid hormone [1-34] (PTH [1-34])
      can have totally opposite effects on osteoblasts. Intermittent stimulation with
      PTH can significantly increase bone mineral density in vitro, mainly through the
      protein kinase A (PKA) signaling pathway, which phosphorylates runt-related
      transcription factor 2 (Runx2). The ClC-3 chloride channel, an important anion
      channel, can also promote osteogenesis via the Runx2 pathway based on recent
      studies. The purpose of our study, therefore, is to research whether the ClC-3
      chloride channel has an effect on PTH osteodifferentiation in MC3T3-E1 cells.
      METHODS AND RESULTS: A cell counting kit (CCK-8) and real-time PCR were used to
      investigate the impact of different PTH stimulation modes on MC3T3-E1 cell
      proliferation and osteogenesis-related gene expression, respectively. We found
      that the minimum inhibitory concentration of PTH was 10-9 M, and the expression
      of alkaline phosphatase (Alpl) and Runx2 were at the highest levels when treated
      with 10-9 M PTH. Next, we used real-time PCR and immunofluorescence technique to
      detect changes in ClC-3 in MC3T3-E1 cells under PTH treatment. The results showed
      higher expression of the ClC-3 chloride channel at 10-9 M intermittent PTH
      administration than in the other groups. Finally, we used the ClC-3 siRNA
      technique to examine the role of the ClC-3 chloride channel in the effect of PTH
      on the osteogenesis of osteoblasts, and we found an obvious decrease in the
      expression of bone sialoprotein (Ibsp), osteocalcin (Bglap), osterix (Sp7), Alpl
      and Runx2, the formation of mineralization nodules as well. CONCLUSIONS: From the
      above data, we conclude that the expression of ClC-3 chloride channels in
      osteoblasts helps them respond to PTH stimulation, which mediates osteogenic
      differentiation.

PMID- 28437477
TI  - Outcomes after antiretroviral therapy during the expansion of HIV services in
      Haiti.
AB  - BACKGROUND: We report patient outcomes after antiretroviral therapy (ART)
      initiation in a network of HIV facilities in Haiti, including temporal trends and
      differences across clinics, during the expansion of HIV services in the country.
      METHODS: We assessed outcomes at 12 months after ART initiation (baseline) using
      routinely collected data on adults (>=15 years) in 11 HIV facilities from July
      2007-December 2013. Outcomes include death (ascertained from medical records),
      lost to follow-up (LTF) defined as no visit > 365 days from ART initiation, and
      retention defined as being alive and attending care >= 365 days from ART
      initiation. Outcomes were compared across calendar year of ART initiation and
      across facilities. Risk factors for death and LTF were assessed using Cox
      proportional hazards and competing risk regression models. RESULTS: Cumulatively,
      9,718 adults initiated ART with median age 37 years (IQR 30-46). Median CD4 count
      was 254 cells/uL (IQR 139-350). Twelve months after ART initiation, 4.4% (95% CI
      4.0-4.8) of patients died, 21.7% (95% CI 20.9-22.6) were LTF, and 73.9% (95% CI
      73.0-74.8) were retained in care. Twelve-month mortality decreased from 13.8%
      among adults who started ART in 2007 to 4.4% in 2013 (p<0.001). Twelve-month LTF
      after ART start was 29.2% in 2007, 18.7% in 2008, and increased to 30.1% in 2013
      (p<0.001). Overall, twelve-month retention after ART start did not change over
      time but varied widely across facilities from 61.1% to 86.5%. CONCLUSION:
      Expansion of HIV services across Haiti has been successful with increasing
      numbers of patients initiating ART and decreasing twelve-month mortality rates.
      However, overall retention has not improved, despite differences across
      facilities, suggesting additional strategies to improve engagement in care are
      needed.

PMID- 28437478
TI  - Metal accumulation by sunflower (Helianthus annuus L.) and the efficacy of its
      biomass in enzymatic saccharification.
AB  - Accumulation of metal contaminants in soil as a result of various industrial and
      anthropogenic activities has reduced soil fertility significantly.
      Phytoextraction of metal contaminants can improve soil fertility and provide
      inexpensive feedstock for biorefineries. We investigated the hyperaccumulation
      capacity of sunflower (Helianthus annuus) biomass by cultivating these plants in
      various concentrations of metal contaminants. Sunflowers were grown in soils
      contaminated with various levels of heavy metals (10-2,000 mg/kg dry soil). The
      degree of metal uptake by different parts of the biomass and the residual
      concentration in the soil were estimated through inductively coupled plasma mass
      spectrometry. An almost 2.5-fold hyperaccumulation of Zn2+ was observed in the
      leaf and flower biomass compared with the concentration in the soil. For the
      subsequent saccharification of biomass with hyperaccumulated contaminants, a
      fungal lignocellulosic consortium was used. The fungal consortium cocktail
      retained more than 95% filter paper activity with 100 mM Ni2+ ions even after 36
      h. The highest saccharification yield (SY, 87.4%) was observed with Ni2+ as the
      contaminant (10 mg/kg dry wt), whereas Pb2+ (251.9 mg/kg dry wt) was the
      strongest inhibitor of biomass hydrolysis, resulting in only a 30% SY.
      Importantly, the enzyme cocktail produced by the fungal consortium resulted in
      almost the same SY (%) as that obtained from a combination of commercial
      cellulase and beta-glucosidase. Significant sugar conversion (61.7%) from H.
      annuus biomass hydrolysate occurred, resulting in the production of 11.4 g/L of
      bioethanol. This is the first study to assess the suitability of phytoremediated
      sunflower biomass for bioethanol production.

PMID- 28437479
TI  - Conformational dynamics of bacterial trigger factor in apo and ribosome-bound
      states.
AB  - The chaperone trigger factor (TF) binds to the ribosome exit tunnel and helps
      cotranslational folding of nascent chains (NC) in bacterial cells and
      chloroplasts. In this study, we aim to investigate the functional dynamics of
      fully-atomistic apo TF and its complex with 50S. As TF accomodates a high
      percentage of charged residues on its surface, the effect of ionic strength on TF
      dynamics is assessed here by performing five independent molecular dynamics (MD)
      simulations (total of 1.3 micro-second duration) at 29 mM and 150 mM ionic
      strengths. At both concentrations, TF exhibits high inter- and intra-domain
      flexibility related to its binding (BD), core (CD), and head (HD) domains. Even
      though large oscillations in gyration radius exist during each run, we do not
      detect the so-called 'fully collapsed' state with both HD and BD collapsed upon
      the core. In fact, the extended conformers with relatively open HD and BD are
      highly populated at the physiological concentration of 150 mM. More importantly,
      extended TF snapshots stand out in terms of favorable docking onto the 50S
      subunit. Elastic network modeling (ENM) indicates significant changes in TF's
      functional dynamics and domain decomposition depending on its conformation and
      positioning on the 50S. The most dominant slow motions are the lateral sweeping
      and vertical opening/closing of HD relative to 50S. Finally, our ENM-based
      efficient technique -ClustENM- is used to sample atomistic conformers starting
      with an extended TF-50S complex. Specifically, BD and CD motions are restricted
      near the tunnel exit, while HD is highly mobile. The atomistic conformers
      generated without an NC are in agreement with the cryo-EM maps available for TF
      ribosome-NC complex.

PMID- 28437480
TI  - Variation of bacterial communities in water and sediments during the
      decomposition of Microcystis biomass.
AB  - The bacterial community composition in water and sediment samples during the
      decomposition of Microcystis biomass were analyzed using the 454 pyrosequencing
      technique. We found dramatic shifts in the bacterial community composition of
      water and sediments after the addition of Microcystis biomass. Among all the
      detected phyla, only Firmicutes was found to be dominant in both water and
      sediment samples. The genus Clostridium sensu stricto was the absolutely dominant
      group in Firmicutes and showed drastic variations with incubation time during the
      decomposition process. Peak values in relative abundance of Clostridium sensu
      stricto appeared in the first few days for water and sediment samples.
      Environmental factors such as pH, dissolved oxygen (DO), and dissolved organic
      carbon (DOC) in water samples showed drastic variations during the decomposing
      process, which might be the prominent forces driving the variation of bacterial
      communities. The abundant genus, Clostridium sensu stricto, were thought to be
      well adapted to higher DOC and turbidity and lower pH and DO conditions. Compared
      with the sediment samples, the decomposition of Microcystis biomass had greater
      influence on the bacterial community composition in water and Clostridium sensu
      stricto might play important roles in the process of Microcystis biomass
      decomposition.

PMID- 28437482
TI  - Study on lockage safety of LNG-fueled ships based on FSA.
AB  - In the present study, formal safety assessment (FSA) is introduced to investigate
      lockage safety of LNG-fueled ships. Risk sources during lockage of LNG-fueled
      ships in four typical scenarios, namely, navigation between two dams, lockage,
      anchorage, and fueling, are identified, and studied in combination with
      fundamental leakage probabilities of various components of LNG storage tanks, and
      simulation results of accident consequences. Some suggestions for lockage safety
      management of LNG-fueled ships are then proposed. The present research results
      have certain practical significance for promoting applications of LNG-fueled
      ships along Chuanjiang River and in Three Gorges Reservoir Region.

PMID- 28437481
TI  - Firemaster(r) 550 and its components isopropylated triphenyl phosphate and
      triphenyl phosphate enhance adipogenesis and transcriptional activity of
      peroxisome proliferator activated receptor (Ppargamma) on the adipocyte protein 2
      (aP2) promoter.
AB  - Firemaster(r) 550 (FM550) is a chemical mixture currently used as an additive
      flame retardant in commercial products, and is comprised of 2-ethylhexyl-2,3,4,5
      tertrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH),
      triphenyl phosphate (TPP), and isopropylated triphenyl phosphate (IPTP). Animal
      and in vitro studies suggest that FM550, TPP and IPTP may have adipogenic effects
      and may exert these effects through PPARgamma activation. Using murine 3T3-L1
      preadipocytes, we investigated the detailed expression of transcription factors
      and adipogenic markers in response to FM550 and its components. Further we
      investigated the mechanism of action of the peroxisome proliferator-activated
      receptor gamma (PPARgamma) on downstream targets of the receptor by focussing on
      the mature adipocyte marker, adipocyte protein 2 (aP2). In addition, we set to
      elucidate the components responsible for the adipogenic effects seen in the FM550
      mixture. We show that FM550 and its components TPP, IPTP, and TBPH, but not TBB
      induced lipid accumulation in a dose-dependent manner. Interestingly, despite
      displaying enhanced lipid accumulation, TBPH did not alter the mRNA or protein
      expression of terminal differentiation markers. In contrast, FM550, TPP, and IPTP
      treatment enhanced lipid accumulation, and mRNA and protein expression of
      terminal differentiation markers. To further delineate the mechanisms of action
      of FM550 and its components we focussed on aP2 promoter activity. For this
      purpose we used the enhancer region of the mouse aP2 promoter using a 584-bp
      reporter construct containing an active PPRE located 5.4 kb away from the
      transcription start site of aP2. Exposure to FM550, IPTP, and TPP significantly
      increased PPARgamma mediated aP2 enhancer activity. Furthermore, we show that TPP
      and IPTP-dependent upregulation of aP2 was significantly inhibited by the
      selective PPARgamma antagonist GW9662. In addition, chromatin immunoprecipitation
      experiments showed that IPTP and TPP treatment led to the recruitment of
      PPARgamma to the regulatory region of aP2.

PMID- 28437483
TI  - Quantitative microvascular analysis of retinal venous occlusions by spectral
      domain optical coherence tomography angiography.
AB  - PURPOSE: To quantitatively evaluate the retinal microvasculature in human
      subjects with retinal venous occlusions (RVO) using optical coherence tomography
      angiography (OCTA). DESIGN: Retrospective, cross-sectional, observational case
      series. PARTICIPANTS: Sixty subjects (84 eyes) were included (20 BRVO, 14 CRVO,
      24 unaffected fellow eyes, and 26 controls). METHODS: OCTA was performed on a
      prototype, spectral domain-OCTA system in the 3x3mm central macular region.
      Custom software was used to quantify morphology and density of retinal
      capillaries using four quantitative parameters. The vasculature of the segmented
      retinal layers and nonsegmented whole retina were analyzed. MAIN OUTCOME
      MEASURES: Fractal dimension (FD), vessel density (VD), skeletal density (SD), and
      vessel diameter index (VDI) within the segmented retinal layers and nonsegmented
      whole retina vasculature. RESULTS: Nonsegmented analysis of RVO eyes demonstrated
      significantly lower FD (1.64+/-0.01 vs 1.715+/-0.002; p<0.001), VD (0.32+/-0.01
      vs 0.432+/-0.002; p<0.001), and SD (0.073+/-0.004 vs 0.099+/-0.001; p<0.001)
      compared to controls. Compared to the fellow eye, FD, VD and SD were lower
      (p<0.001), and VDI was higher (p<0.001). FD, VD, and SD progressively decreased
      as the extent (or type) of RVO increased (control vs BRVO vs CRVO; p<0.001). In
      the unaffected fellow eye FD, VD and SD showed significant differences when
      compared to control eyes or affected RVO eyes (p<0.001). CONCLUSIONS:
      Quantitative OCTA of the central 3x3mm macular region demonstrates significant
      differences in capillary density and morphology among subjects with BRVO and CRVO
      compared to controls or unaffected fellow eyes in all vascular layers. The
      unaffected fellow eyes also demonstrate significant differences when compared to
      controls. OCTA allows for noninvasive, layer-specific, quantitative evaluation of
      RVO-associated microvascular changes.

PMID- 28437484
TI  - ECG-ViEW II, a freely accessible electrocardiogram database.
AB  - The Electrocardiogram Vigilance with Electronic data Warehouse II (ECG-ViEW II)
      is a large, single-center database comprising numeric parameter data of the
      surface electrocardiograms of all patients who underwent testing from 1 June 1994
      to 31 July 2013. The electrocardiographic data include the test date, clinical
      department, RR interval, PR interval, QRS duration, QT interval, QTc interval, P
      axis, QRS axis, and T axis. These data are connected with patient age, sex,
      ethnicity, comorbidities, age-adjusted Charlson comorbidity index, prescribed
      drugs, and electrolyte levels. This longitudinal observational database contains
      979,273 electrocardiograms from 461,178 patients over a 19-year study period.
      This database can provide an opportunity to study electrocardiographic changes
      caused by medications, disease, or other demographic variables. ECG-ViEW II is
      freely available at http://www.ecgview.org.

PMID- 28437485
TI  - T cell function is dispensable for intracranial aneurysm formation and
      progression.
AB  - Given the social importance of intracranial aneurysm as a major cause of a lethal
      subarachnoid hemorrhage, clarification of mechanisms underlying the pathogenesis
      of this disease is essential for improving poor prognosis once after rupture.
      Previous histopathological analyses of human aneurysm walls have revealed the
      presence of T cells in lesions suggesting involvement of this type of cell in the
      pathogenesis. However, it remains unclear whether T cell actively participates in
      intracranial aneurysm progression. To examine whether T cell is involved in
      aneurysm progression, intracranial aneurysm model of rat was used. In this model,
      aneurysm is induced by increase in hemodynamic force loaded on bifurcation site
      of intracranial arteries where aneurysms are developed. Deficiency in T cells and
      pharmacological inhibition of T cell function were applied to this model. CD3
      positive T cells were present in human aneurysm walls, whose number was
      significantly larger compared with that in control arterial walls. Deficiency in
      T cells in rats and pharmacological inhibition of T cell function by oral
      administration of Cyclosporine A both failed to affect intracranial aneurysm
      progression, degenerative changes of arterial walls and macrophage infiltration
      in lesions. Although T cells are detectable in intracranial aneurysm walls, their
      function is dispensable for macrophage-mediated inflammation and degenerative
      changes in arterial walls, which presumably leads to intracranial aneurysm
      progression.

PMID- 28437486
TI  - Prediction of crime occurrence from multi-modal data using deep learning.
AB  - In recent years, various studies have been conducted on the prediction of crime
      occurrences. This predictive capability is intended to assist in crime prevention
      by facilitating effective implementation of police patrols. Previous studies have
      used data from multiple domains such as demographics, economics, and education.
      Their prediction models treat data from different domains equally. These methods
      have problems in crime occurrence prediction, such as difficulty in discovering
      highly nonlinear relationships, redundancies, and dependencies between multiple
      datasets. In order to enhance crime prediction models, we consider environmental
      context information, such as broken windows theory and crime prevention through
      environmental design. In this paper, we propose a feature-level data fusion
      method with environmental context based on a deep neural network (DNN). Our
      dataset consists of data collected from various online databases of crime
      statistics, demographic and meteorological data, and images in Chicago, Illinois.
      Prior to generating training data, we select crime-related data by conducting
      statistical analyses. Finally, we train our DNN, which consists of the following
      four kinds of layers: spatial, temporal, environmental context, and joint feature
      representation layers. Coupled with crucial data extracted from various domains,
      our fusion DNN is a product of an efficient decision-making process that
      statistically analyzes data redundancy. Experimental performance results show
      that our DNN model is more accurate in predicting crime occurrence than other
      prediction models.

PMID- 28437487
TI  - Crop and varietal diversification of rainfed rice based cropping systems for
      higher productivity and profitability in Eastern India.
AB  - Rice-rice system and rice fallows are no longer productive in Southeast Asia.
      Crop and varietal diversification of the rice based cropping systems may improve
      the productivity and profitability of the systems. Diversification is also a
      viable option to mitigate the risk of climate change. In Eastern India, farmers
      cultivate rice during rainy season (June-September) and land leftovers fallow
      after rice harvest in the post-rainy season (November-May) due to lack of
      sufficient rainfall or irrigation amenities. However, in lowland areas,
      sufficient residual soil moistures are available in rice fallow in the post-rainy
      season (November-March), which can be utilized for raising second crops in the
      region. Implementation of suitable crop/varietal diversification is thus very
      much vital to achieve this objective. To assess the yield performance of rice
      varieties under timely and late sown conditions and to evaluate the performance
      of dry season crops following them, three different duration rice cultivars were
      transplanted in July and August. In dry season several non-rice crops were sown
      in rice fallow to constitute a cropping system. The results revealed that tiller
      occurrence, biomass accumulation, dry matter remobilization, crop growth rate,
      and ultimately yield were significantly decreased under late transplanting. On an
      average, around 30% yield reduction obtained under late sowing may be due to low
      temperature stress and high rainfall at reproductive stages of the crop. Dry
      season crops following short duration rice cultivars performed better in terms of
      grain yield. In the dry season, toria was profitable when sown earlier and if
      sowing was delayed greengram was suitable. Highest system productivity and
      profitability under timely sown rice may be due to higher dry matter
      remobilization from source to sink. A significant correlation was observed
      between biomass production and grain yield. We infer that late transplanting
      decrease the tiller occurrence and assimilate remobilization efficiency, which
      may be responsible for the reduced grain yield.

PMID- 28437489
TI  - The Patellofemoral Compartment: Making Sense of It.

PMID- 28437488
TI  - The novel carboxylesterase 1 variant c.662A>G may decrease the bioactivation of
      oseltamivir in humans.
AB  - BACKGROUND: Human carboxylesterase 1 (CES1) is a serine esterase that hydrolyses
      various exogenous and endogenous compounds including oseltamivir, a prodrug used
      to treat influenza. A novel CES1 c.662A>G single nucleotide polymorphism (SNP)
      was predicted to decrease CES1 enzymatic activity in an in silico analysis. This
      study evaluated the effect of the c.662A>G SNP on the pharmacokinetics (PK) of
      oseltamivir in humans. METHODS: A single oral dose of oseltamivir at 75 mg was
      administered to 20 healthy subjects, 8 heterozygous c.662A>G carriers (c.662AG)
      and 12 non-carriers (c.662AA). The concentrations of oseltamivir and its active
      metabolite, oseltamivir carboxylate, were measured in plasma and urine using a
      validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The
      PK parameters were calculated using a noncompartmental method. The geometric mean
      ratios (GMR, c.662AG to c.662AA) of the PK parameters and their 90% confidence
      intervals (CI) were calculated. RESULTS: The systemic exposure to oseltamivir, as
      assessed by the AUC0-48h of oseltamivir, was increased by 10% in c.662AG
      subjects, whereas the AUC0-48h of oseltamivir carboxylate was 5% lower in c.662AG
      subjects. The GMR and 90% CI of the metabolic ratio (AUC0-48h, Oseltamivir
      carboxylate/AUC0-48h, Oseltamivir) was 0.87 (0.66-1.14). The amount of unchanged
      oseltamivir excreted in the urine was increased by 15% in subjects with the
      c.662AG genotype. CONCLUSIONS: This result suggests that CES1 enzymatic activity
      may be decreased in these heterozygous allele carriers, although further studies
      are warranted to investigate the clinical implications of this genetic variation
      on CES1 substrate drugs. TRIAL REGISTRATION: ClinicalTtrials.gov NCT01902342.

PMID- 28437490
TI  - The Diagnosis and Initial Treatment of Patellofemoral Disorders.
AB  - Our purpose is to provide simple guidelines for the diagnosis and early care of
      patellofemoral disorders. Any clinician who treats knee problems, including
      family practitioners, rheumatologists, orthopedic surgeons, or physical
      therapists, must know how to make the correct diagnosis, or at least a
      presumptive diagnosis, at the initial visit. This can avoid unneeded and costly
      tests, ineffective treatment, and even damaging exercises and unnecessary
      surgery. The diagnosis of patellofemoral disorders is confusing because they can
      have many causes. That is, the etiology of patellofemoral disorders is
      multifactorial. To dispel this confusion and simplify the process, we use a
      clinical classification based on etiology. Within that framework are 7 key
      abnormalities or factors that can cause both patellofemoral pain and instability:
      vastus medialis obliquus deficiency, medial patellofemoral ligament laxity,
      lateral retinaculum tightness, increased quadriceps angle, hip abductor weakness,
      patella alta, and trochlear dysplasia. At the initial evaluation, the clinician
      can assess for these abnormalities through history-taking, physical examination,
      and standard radiography. Any abnormalities identified, along with their
      severity, can be used to arrive at a diagnosis, or a presumptive diagnosis, and
      begin early nonoperative treatment. The clinician does not need magnetic
      resonance imaging at this point, unless a presumptive diagnosis cannot be made or
      a more complex problem is suggested.

PMID- 28437491
TI  - Correct Positioning of the Medial Patellofemoral Ligament: Troubleshooting in the
      Operating Room.
AB  - Medial patellofemoral ligament (MPFL) reconstruction is often required after
      failed nonoperative management of lateral patellar instability. It is important
      to properly re-create the native ligament to avoid altering patellofemoral
      biomechanics. Such alterations can cause knee stiffness, anterior knee pain, and
      patellofemoral chondrosis. Incorrect femoral location is the most common mistake
      that affects MPFL graft biomechanics. Authors have described multiple
      radiographic and anatomical landmarks that assist in determining the appropriate
      location, and time should be taken to accurately localize this position.
      Regardless of the reconstruction technique used, the knee should be taken through
      its full range of motion, before the MPFL graft is secured, to test the
      biomechanics and reduce the risk of postoperative complications. If the graft
      becomes too tight as the knee moves into flexion, the femoral location is too
      proximal and should be adjusted ("high and tight"). By contrast, if the graft
      becomes too loose in flexion, then the femoral location is too distal ("low and
      loose"). These simple rules can be used to intraoperatively troubleshoot the
      tunnel placement.

PMID- 28437492
TI  - Clinical Rehabilitation of Anterior Knee Pain: Current Concepts.
AB  - Rehabilitation is the hallmark of the nonoperative treatment of anterior knee
      pain (AKP). Whether a patient has had appropriate rehabilitation can be assessed
      in the office with a selection of basic and advanced screening tests. Most
      important, providing specific instructions in your referral to a therapist
      skilled in treating patients with AKP can ensure that any identified deficits are
      appropriately addressed. The etiology of AKP is multifactorial. Whatever its
      "cause," AKP alters neuromuscular function, and correcting these altered body
      movement patterns will benefit the patient. Understanding how to assess and guide
      treatment of neuromuscular deficits in this population is essential for managing
      care and optimizing outcomes. In this article, factors associated with the
      diminished neuromuscular control seen in AKP are reviewed, appropriate
      rehabilitation concepts are discussed, and practical strategies are provided that
      can aid in identifying neuromuscular deficits and the need for further
      rehabilitation.

PMID- 28437493
TI  - The Role of Medial Patellofemoral Ligament Repair and Imbrication.
AB  - Repair, reefing, and advancement of the medial patellofemoral ligament (MPFL) and
      medial retinacular structures can be performed as an isolated procedure or in
      conjunction with distal realignment procedures for patients with patellar
      instability. Although various operative techniques have been described,
      understanding the appropriate clinical indications and MPFL injury patterns
      ultimately determines the success or failure of the procedure. MPFL repair is
      best indicated in the acute setting, particularly if there is a patella- or
      femoral-based avulsion. If MPFL repair is being considered, and there is no
      evidence of avulsion on plain radiographs, magnetic resonance imaging can be used
      to examine the pattern and extent of the MPFL injury. In cases of chronic
      patellar instability, medial retinacular reefing or imbrication is best
      considered in conjunction with other procedures that address common pathology
      associated with chronic instability. These procedures include distal realignment,
      trochleoplasty, and distal femoral osteotomy.

PMID- 28437494
TI  - Patellofemoral Pain: An Enigma Explained by Homeostasis and Common Sense.
AB  - We present a rational, scientific, low-risk approach to patellofemoral pain
      (anterior knee pain) based on an understanding of tissue homeostasis. Loss of
      tissue homeostasis from overload and/or injury produces pain. Bone overload and
      synovial inflammation are common sources of such pain. Chondromalacia and
      malalignment are findings that almost always do not need to be "corrected" to
      relieve pain. Patience and persistence in nonoperative care results in consistent
      success. Surgery should be rare and done only after extensive nonoperative
      management and in the setting of clearly defined pathology. Rational surgical
      treatment is explained in the context of restoring tissue homeostasis to relieve
      pain.

PMID- 28437495
TI  - A Practical Guide to Understanding and Treating Patellofemoral Pain.
AB  - There is no shortcut to accurate diagnosis in the patellofemoral pain patient.
      Most important in the process is a desire and ability to specifically identify
      the structural and biomechanical origin of pain. This can be elusive and often
      requires a careful analysis of all factors affecting the patient, including
      documenting his or her specific history of pain origin and specific treatments to
      date, and acknowledging the patient's localization of the pain origin. Many
      patients can pinpoint the site of pain origin when given the time and
      encouragement to do so. Of all sources of anterior knee pain, intractable pain
      related to diffuse patella articular cartilage deficiency can be most
      troublesome, particularly in a young person. Rest and removal of inciting causes
      of pain must always be the first option. Surgery is usually unnecessary, but may
      be extremely helpful in recalcitrant cases. Releasing excessively tight, painful
      contracture, removing unstable fragments and impinging synovial tissue, and
      sometimes permanently unloading a well-documented painful distal or lateral
      articular lesion by anteromedial tibial tubercle transfer will eliminate
      resistant pain in even the most resistant anterior knee pain patient.

PMID- 28437496
TI  - Novel Solution for Massive Glenoid Defects in Shoulder Arthroplasty: A Patient
      Specific Glenoid Vault Reconstruction System.
AB  - Complex glenoid deformities present the most difficult challenges in shoulder
      arthroplasty. These deformities may be caused by severe degenerative or
      congenital deformity, posttraumatic anatomy, tumor, or, in most cases, bone loss
      after glenoid failure in anatomical total shoulder arthroplasty. Methods of
      treating severe bone loss have included inlay and onlay bone-graft options with
      augmented fixation and, in severe cases, salvage hemiarthroplasty with limited
      goal expectations. Unfortunately, none of these methods has provided consistently
      satisfactory reproducible results. In fact, each has had high rates of failure
      and complications. Borrowing from hip and knee arthroplasty surgeons' experience
      in using CAD/CAM (computer-aided design/computer-aided manufacturing) patient
      specific implants to fill significant bony defects, Dr. D. M. Dines developed a
      glenoid vault reconstruction system (VRS) in conjunction with the Comprehensive
      Shoulder Arthroplasty System (Zimmer Biomet) to treat severe glenoid bone
      deficiency. The VRS is patient-specific; each case involves making a preoperative
      plan based on 3-dimensional reconstruction of a 2-dimensional computed tomography
      scan. The patient-specific implant and instrumentation that are created are used
      to reconstruct the deformed glenoid in an anatomical position without the need
      for additional bone graft. In this article, we describe the implant and its
      indications, technical aspects of production, and surgical technique.

PMID- 28437497
TI  - A Rare Case of Spontaneous Fusion of the Knee.
AB  - To our knowledge, this article is the first report of a case of spontaneous and
      progressive bony fusion of a knee joint without a prior diagnosis of inflammatory
      or septic arthritis or surgical arthrodesis.

PMID- 28437498
TI  - Superior Mesenteric Artery Syndrome as a Complication of Scoliosis Surgery.
AB  - Superior mesenteric artery (SMA) syndrome is a rare and potentially life
      threatening complication of scoliosis surgery. The anatomical relationship of the
      duodenum and the superior mesenteric artery, the correction of angular deformity
      of the spine, and the normal adolescent growth spurt all contribute to the
      condition. We report the case of a 14-year-old boy who had a history of
      idiopathic scoliosis and presented with bilious vomiting that had persisted for 7
      days after posterior T9-L4 fusion with instrumentation. After an unremarkable
      immediate postoperative course, on postoperative day 19 the patient presented to
      the emergency department with abdominal pain, nausea, and vomiting. Unrelenting
      brown vomitus, abdominal pain, and a 20-lb weight loss were noted. A series of
      upper gastrointestinal radiographs confirmed a diagnosis of SMA syndrome. A
      nasojejunal tube was placed, and nutritional rehabilitation was optimized. We
      highlight this case for its rarity and emphasize the importance of maintaining a
      high index of suspicion when evaluating a child who has had spinal deformity
      correction and presents with postoperative gastrointestinal complaints. Early
      recognition of the nonspecific symptoms of abdominal pain, abdominal distension,
      bilious or projectile vomiting, hypoactive bowel sounds, and anorexia plays a key
      role in post-scoliosis surgery and is crucial in preventing the severe morbidity
      and mortality associated with SMA syndrome.

PMID- 28437499
TI  - Systemic Hypothermia as Treatment for an Acute Cervical Spinal Cord Injury in a
      Professional Football Player: 9-Year Follow-Up.
AB  - The following report provides clinical follow-up on a National Football League
      player who sustained a complete cervical spinal cord injury (SCI) while tackling
      an opposing player in 2007. He received prompt medical and surgical care based on
      then-current recommendations, but was also treated with systemic hypothermia soon
      after his injury, which was controversial at the time. Since then, smaller
      randomized human studies have described the tolerable safety profile, efficacy,
      and potential benefits of this intervention in acute SCI in humans. Now, modest
      systemic hypothermia can be one of many tools considered in the treatment of
      acute SCI. Before it can become the standard of care, however, additional larger
      prospective randomized studies need to be completed. The patient described in
      this article had long-term excellent clinical results, with residual deficits of
      occasional tingling in fingertips and toe tips, although the patient continues to
      slowly improve.

PMID- 28437500
TI  - Removal of the Distal Aspect of a Broken Tibial Nail.
AB  - Nail breakage is a known complication of intramedullary nail (IMN) fixation of
      tibial fractures. Several case reports have described unique methods used to
      facilitate removal of broken IMNs. In this article, we describe an efficient
      technique for extracting broken tibial IMNs-a technique that can be used before
      attempting more invasive extraction methods.

PMID- 28437501
TI  - Pronator Teres Myotendinous Tear.
AB  - Pronator teres muscle strain is a rare sporting injury reported thus far only in
      cricket and golf players. The injury appears to occur when the sporting club or
      racket strikes the ground during a forceful swing and causes the elbow to
      experience an eccentric force during resisted elbow flexion and pronation. On
      initial presentation, this injury can be mistaken for injury to the medial ulnar
      collateral ligament, or exacerbation of medial epicondylitis. On examination,
      bruising and tenderness distal to the elbow over the course of the pronator teres
      are often present. Advanced imaging confirms the diagnosis and can help in
      grading injury severity. In this article, we report the case of a patient who was
      conservatively treated, and returned to function and sport by 6 weeks after a
      period of rest and restricted activities. The prognosis is excellent for even
      high-grade strains. Complete return to sporting function without residual
      weakness is expected.

PMID- 28437502
TI  - Combined Anterior-Posterior Decompression and Fusion for Cervical Spondylotic
      Myelopathy.
AB  - We conducted a study to evaluate the operative details, perioperative
      complications, and short-term outcomes associated with combined anterior
      posterior decompression and fusion (CAPDF) for treating cervical spondylotic
      myelopathy (CSM). We retrospectively reviewed the charts of 21 patients who
      underwent CAPDF at our institution. Pertinent information, including
      demographics, surgery indication, perioperative complications, operative time,
      levels fused (and number of levels fused) anteriorly and posteriorly, estimated
      blood loss, and length of stay, was gathered. Outpatient follow-up data were
      available for 20 of the 21 patients, and postoperative neurologic status was
      evaluated with Nurick grades as well as by subjective means. Mean age was 62.1
      years (range, 44-79 years). Of the 21 patients, 9 were female, and 12 were male.
      Before surgery, all patients had a diagnosis of CSM of varying degree. Mean
      number of levels fused was 2 (range, 1-3) anteriorly and 3 (range, 1-4)
      posteriorly. Mean operative time, which included patient repositioning, was 4
      hours 55 minutes (range, 3:04-6:22). Mean estimated blood loss was 131 mL (range,
      55-278 mL), and mean length of stay was 5 days (range, 2-10 days). The most
      commonly encountered complication was dysphagia (28.6%, 6/21). Neither neurologic
      instability nor mortality was observed after surgery. Neurologic status was
      subjectively improved for 19 patients and unimproved for 1 patient; no patient's
      neurologic status was worse. Mean Nurick grade was 1.9 before surgery and 1.1
      after surgery (mean difference, 0.80; P < .001), at a mean follow-up of 96 days
      (range, 51-149 days). When indicated, CAPDF is an efficient and effective
      treatment for CSM. This study found the procedure to be associated with minor
      complications, no new neurologic deficits, and high levels of neurologic
      improvement. The positive short-term outcomes and low rate of long-term
      complications in our study, combined with data from previous comparative studies,
      suggest that same-day surgery is superior to staged surgery.

PMID- 28437503
TI  - Subscapularis Tenotomy Versus Lesser Tuberosity Osteotomy for Total Shoulder
      Arthroplasty: A Systematic Review.
AB  - Subscapularis tenotomy (ST) has been the standard method of mobilizing the
      subscapularis during the approach to a total shoulder arthroplasty (TSA).
      Recently, lesser tuberosity osteotomy (LTO), which avoids subscapularis
      complications, has gained in popularity. We performed a systematic review to
      elucidate any differences in clinical or radiographic outcomes between ST and
      LTO. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analyses) guidelines, we identified clinical and/or radiographic TSA studies with
      minimum mean 2-year follow-up and level I to IV evidence. Twenty studies (1420
      shoulders, 1392 patients) were included in the study. The ST group had
      significantly more patients with osteoarthritis (P = .03) and fewer patients with
      posttraumatic arthritis (P = .04). At final follow-up, mean (SD) forward
      elevation improvements were significantly (P < .01) larger for the ST group,
      +50.9 degrees  (17.5 degrees ) than for the LTO group, +31.3 degrees  (0.9
      degrees ). Complication rates were almost identical, but the ST group showed a
      trend (P = .31) toward fewer revisions (10.0% vs 16.2%). There were no
      differences in Constant scores, pain scores, or radiolucencies. Both approaches
      (ST, LTO) produced excellent outcomes. ST may result in wider range of motion and
      fewer revisions, but more studies are needed to further evaluate these results.

PMID- 28437504
TI  - Effect of Plate in Close Proximity to Empty External-Fixation Pin Site on Long
      Bone Torsional Strength.
AB  - Complex tibia fractures are often provisionally stabilized with external fixation
      prior to definitive fracture fixation. Bicortical defects, such as those left
      after removal of a fixator pin, can decrease the torsional strength of long bone.
      Evaluating the effect of subsequent plate fixation in close proximity to a defect
      on the torsional strength of the tibia is the purpose of this study. Eight groups
      of 5 fourth-generation left composite tibias were tested to failure in torsion.
      The experimental plated groups consisted of bicortical defects at 3 cm, 2 cm, and
      1 cm distal to the plate end, with 1 plated group without a defect. The control
      groups consisted of equivalent defects in the same distal longitudinal locations,
      without plates attached, as well as an unplated group without a defect. There
      were no statistical differences in torsional stiffness or failure torque between
      any of the groups. The mode of failure for all specimens with bicortical defects
      was a spiral fracture that bisected the axis of the defect. Based on the results
      of this composite tibia study, varying the proximity of a bicortical defect to a
      plate does not affect the torsional stiffness or torsional failure strength of
      the bone.

PMID- 28437505
TI  - Guidelines for Treatment of Lateral Patella Dislocations in Skeletally Mature
      Patients.
AB  - The incidence of lateral patella dislocations is high, particularly in young
      females. Beside traumatic cases, many patients present with specific anatomical
      factors that predispose to lateral patella dislocations (torsional abnormalities
      of the femur or the tibia, trochlea dysplasia, patella alta, etc). It is of
      utmost importance to correct those pathologic factors during concomitant
      procedures as isolated reconstructions of the medial patellofemoral ligament
      would fail in the presence of severe anatomic risk factors. This article provides
      a comprehensive instruction on how to analyze the risk factors for lateral
      patella dislocation (anatomy, physical examination, imaging) and reports the
      authors' favorite surgical techniques. Moreover, treatment algorithms are
      provided for primary and recurrent cases of lateral patella dislocation.

PMID- 28437506
TI  - Treatment of Unstable Trochanteric Femur Fractures: Proximal Femur Nail Versus
      Proximal Femur Locking Compression Plate.
AB  - Unstable trochanteric femur fractures are common fractures that are difficult to
      manage. We conducted a prospective study to compare functional outcomes and
      complications of 2 different implant designs, proximal femur nail (PFN) and
      proximal femur locking compression plate (PFLCP), used in internal fixation of
      unstable trochanteric femur fractures. On hospital admission, 48 patients with
      unstable trochanteric fractures were randomly assigned (using a sealed envelope
      method) to treatment with either PFN (24 patients) or PFLCP (24 patients).
      Perioperative data and complications were recorded. All cases were followed up
      for 2 years. The groups did not differ significantly (P > .05) in operative time,
      reduction quality, complications, hospital length of stay, union rate, or time to
      union. Compared with the PFLCP group, the PFN group had shorter incisions and
      less blood loss. Regarding functional outcomes, there was no significant
      difference in mean Harris Hip Score (P = .48) or Palmer and Parker mobility score
      (P = .58). Both PFN and PFLCP are effective in internal fixation of unstable
      trochanteric femur fractures.

PMID- 28437507
TI  - Effects of Experimental Pain and Lidocaine on Mechanical Somatosensory Profile
      and Face Perception.
AB  - AIMS: To assess the effects of experimental muscle pain and topical lidocaine
      applied to the skin overlying the masseter muscle on the mechanical somatosensory
      profile and face perception of the masseter muscle in healthy participants.
      METHODS: A total of 28 healthy participants received a 45-minute application of a
      lidocaine or placebo patch to the skin overlying the masseter muscle followed by
      one injection of 0.2 mL sterile solution of monosodium glutamate. Measurements
      were taken four times during each session of quantitative sensory testing (QST)
      (T0 = baseline, T1 = 45 minutes after patch application, T2 = immediately after
      glutamate injection, and T3 = 25 minutes after the glutamate injection), and the
      following variables were measured: mechanical detection threshold (MDT),
      mechanical pain threshold (MPT), pressure pain threshold (PPT), pain report (pain
      on palpation, pain spreading on palpation, and pain intensity), pain drawing, and
      perceptual distortion. Multi-way within-subjects analysis of variance (ANOVA) was
      applied to the data. RESULTS: The highest MDTs were present at T2 (F = 49.28, P <
      .001), the lowest PPTs were present at T2 and T3 (F = 21.78, P < .001), and the
      largest magnitude and area of perceptual distortion were reported at T2 (F >
      6.48, P < .001). CONCLUSION: Short-lasting experimental muscle pain was capable
      of causing loss of tactile sensitivity as well as perceptual distortion of the
      face, regardless of preconditioning with a topical lidocaine patch. Short-term
      application of a lidocaine patch did not significantly affect the mechanical
      somatosensory profile.

PMID- 28437508
TI  - Comparative Evaluation of Anesthetic Efficacy of 2% Lidocaine, 4% Articaine, and
      0.5% Bupivacaine on Inferior Alveolar Nerve Block in Patients with Symptomatic
      Irreversible Pulpitis: A Prospective, Randomized, Double-blind Clinical Trial.
AB  - AIMS: To compare the anesthetic efficacy of 1.8 mL of 2% lidocaine with 1:200,000
      epinephrine, 4% articaine with 1:100,000 epinephrine, and 0.5% bupivacaine with
      1:200,000 epinephrine on producing inferior alveolar nerve block (IANB) in
      patients with symptomatic irreversible pulpitis. METHODS: A total of 91 adult
      patients who were actively experiencing mandibular molar pain were involved in
      this study. The patients were randomly divided into three groups on the basis of
      the anesthetic solution used. The first group received IANB with 1.8 mL of 2%
      lidocaine with 1:200,000 epinephrine, the second group received IANB with 4%
      articaine with 1:100,000 epinephrine, and the third group received IANB with 0.5%
      bupivacaine with 1:200,000 epinephrine. After 15 minutes of IANB, conventional
      endodontic access preparation was started. The pain during the treatment was
      noted on a Heft-Parker visual analog scale (HP VAS). The primary outcome measure
      was anesthetic success, and anesthesia was considered successful if the patient
      reported no pain or weak/mild pain (HP VAS score < 55 mm) during endodontic
      treatment (pulp access and canal preparation procedures). The data were analyzed
      with one-way analysis of variance and chi-square test. RESULTS: The anesthetic
      success rates of 2% lidocaine, 4% articaine, and 0.5% bupivacaine were 23%, 33%,
      and 17%, respectively. The differences were statistically insignificant (P >
      .05). CONCLUSION: The 2% lidocaine solution used for IANB had similar success
      rates when compared with 4% articaine and 0.5% bupivacaine.

PMID- 28437509
TI  - Thermal Perception as a Key Factor for Assessing Effects of Trigeminal Nerve
      Injury.
AB  - AIMS: To conduct a functional examination using multimodal exploration of a
      sample of patients with iatrogenic trigeminal nerve injury to understand the
      underlying mechanisms of neuropathic pain following trigeminal nerve injury.
      METHODS: Subjective and objective symptoms and responses to thermal and
      electrical quantitative sensory testing (QST) were evaluated in 85 patients with
      unilateral trigeminal nerve injury. Objective symptoms were measured by seven
      clinical sensory tests. Thermal QST included cold detection threshold (CDT), warm
      detection threshold (WDT), and heat pain threshold (HPT). Electrical current
      perception threshold was performed with electrical stimuli of 2,000, 250, and 5
      Hz. The time since injury was included as a possible independent variable. The
      data were analyzed using chi-square test, independent t test, Mann Whitney U
      test, one-way analysis of variance (ANOVA), and Kruskal-Wallis test. Further
      analyses with Pearson correlation analysis, Spearman rank correlation analysis,
      and cluster analysis were applied. RESULTS: Unlike objective symptoms, thermal
      and electrical QST values and subjective symptoms did not improve in patients
      with an old injury. Thermal QST, particularly WDT, showed the highest positive
      correlation with subjective symptoms in all tests. Cluster analysis of the
      thermal QST values identified three subgroups: cluster 1, which was characterized
      by prominent cold and warm hypoesthesia; cluster 2, which presented elevated WDT;
      and cluster 3, which showed the smallest thermal differences for all thermal
      variables but had the highest proportion of neuropathic pain. CONCLUSION: These
      findings have demonstrated that thermal QST is a suitable tool for evaluating and
      characterizing the sensory effects of trigeminal nerve injury. Three subgroups
      with different thermosensory profiles showed that the less the damage, the more
      neuropathic pain occurs. The loss of warm perception in particular might play a
      pivotal role in the chronicity and severity of subjective sensory symptoms.

PMID- 28437510
TI  - Somatosensory Profile Changes Evoked by Topical Application of Capsaicin to the
      Tongue in Healthy Individuals.
AB  - AIMS: To assess the effect of topical application of capsaicin to the tongue as a
      surrogate model of burning mouth syndrome (BMS) on somatosensory sensitivity by
      using a standardized battery of quantitative sensory testing (QST) in healthy
      volunteers. METHODS: This study comprised two experimental sessions (experimental
      [capsaicin] and control [Vaseline]) with QST in 16 healthy women. The examiner
      applied capsaicin or Vaseline to the tongue tip for 5 minutes. Each participant
      kept their tongue tip in contact with the capsaicin/Vaseline at the bottom of a
      disposable cup for 5 minutes, during which time the participant rated the
      perceived intensity of the tongue pain every 30 seconds on an electronic 0 to 10
      visual analog scale (VAS). QST was performed on the tongue tip before and
      immediately after application in each session. The QST data were analyzed by two
      way analysis of variance (ANOVA). RESULTS: Mean +/- standard error of the mean
      (SEM) of VAS pain scores during the capsaicin and control sessions were 8.2 +/-
      0.5 and 1.9 +/- 0.2, respectively. The peak of the perceived pain in the
      capsaicin session was significantly higher than in the control session (P <
      .001). In the capsaicin session, the postapplication heat pain threshold (HPT)
      was significantly higher than the preapplication HPT, and the postapplication
      cold detection threshold (CDT) and mechanical pain threshold (MPT) were
      significantly lower than before application (P < .001). The average z scores
      showed a significant somatosensory loss regarding CDT. In the control session,
      there were no differences between preapplication and postapplication values.
      CONCLUSION: Topical application of capsaicin to the tongue tip changed
      somatosensory sensitivity in healthy participants.

PMID- 28437511
TI  - Online Information on the Treatment of Burning Mouth Syndrome: Quality and
      Readability.
AB  - AIMS: To evaluate the quality and readability of online information about the
      treatment of burning mouth syndrome (BMS). METHODS: An internet search using the
      phrase "burning mouth syndrome treatment" was carried out on the Google search
      engine (www.google.co.uk) on 8 June 2015, and the first 100 websites listed were
      examined. Data collection included DISCERN score, the Journal of the American
      Medical Association (JAMA) benchmarks for website analysis score, the presence of
      the Health on the Net (HON) Foundation seal, and the Flesch Reading Ease Score
      (FRES). Descriptive statistics were performed using Microsoft Office Excel.
      RESULTS: The search strategy initially yielded 635,000 links; following the
      application of the exclusion criteria, 53 sites remained for analysis. The
      overall DISCERN score varied between websites, with half of all websites
      achieving an overall score of 2 and none of these websites achieving the maximum
      score of 5. The mean score +/- standard deviation (SD) was 2.4 +/- 0.7. Only 10
      (18.9%) of the websites achieved the four JAMA benchmarks while 3 (5.7%) of the
      websites did not achieve any of them. Only 9 (17%) displayed the HON seal. The
      FRES of the websites ranged from 32.4 to 82.2; the mean +/- SD rating was 55.4 +/
      10.7, which is considered to reflect fairly difficult reading. CONCLUSION: The
      information available online about BMS is of questionable quality and content.
      Perhaps engaging patients in determining what type and format of information they
      desire when searching online for health information could guide clinicians and
      researchers alike in providing reliable and readable information sources.

PMID- 28437513
TI  - Prevalence of Temporomandibular Disorders in the Northern Finland Birth Cohort
      1966.
AB  - AIMS: To investigate the prevalence of temporomandibular disorders (TMD) in the
      46-year-old cohort subjects from the Northern Finland Birth Cohort 1966 (NFBC
      1966). METHODS: Altogether, 1,962 subjects (1,050 women, 912 men) participated in
      a clinical medical and dental examination and responded to questionnaires in 2012
      to 2013. The stomatognathic examination was performed according to a modified
      protocol of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD).
      Pearson's chi-square test and Fisher's exact test were used to analyze the signs
      of TMD between genders, and logistic regression models were used to analyze the
      relationship between self-reported pain associated with TMD and modified DC/TMD
      protocol (P < .05). RESULTS: Of the subjects available for analyses, 18.5%
      responded positively to the self-reported screening question for pain related to
      TMD. The most common signs of TMD were clicking in the temporomandibular joint
      (TMJ) (26.2%) and palpation pain in the masticatory muscles (11.2%). Women had
      signs of TMD more often than men (P < .05). The most common diagnosis was disc
      displacement with reduction (7.0%). Myalgia, arthralgia, disc displacement with
      reduction, and degenerative joint disease diagnoses were statistically
      significantly more common in women than in men (P < .05). The prevalence of TMD
      signs among the cohort subjects was 34.2%. CONCLUSION: The most common sign of
      TMD was clicking in the TMJ and the most common TMD diagnosis was disc
      displacement with reduction. The prevalence of TMD signs among the examined
      cohort subjects was 34.2%. TMD was diagnosed in women more often than in men. The
      results are comparable with other corresponding population-based studies in
      adults.

PMID- 28437514
TI  - A Retrospective Study on Possible Predictive Factors for Long-term
      Temporomandibular Joint Degeneration and Impaired Mobility in Juvenile Arthritis
      Patients.
AB  - AIMS: To determine possible predictive factors for long-term temporomandibular
      joint (TMJ) degeneration and dysfunction in juvenile idiopathic arthritis (JIA)
      patients. METHODS: A total of 94 patients (77% female) who had received a JIA
      diagnosis in an outpatient rheumatology clinic from 1993 to 1994 at a mean +/-
      standard deviation age of 8.3 +/- 4.53 years were included in the study. At
      inclusion, TMJ status regarding condylar degeneration was assessed
      orthopantomographically and given a Rohlin and Petersson score of 0 or >= 1. The
      maximal mouth opening (MMO) was also measured. Data on possible predictors were
      gathered retrospectively from the consultation at intake: gender, age at JIA
      onset, JIA subtype, physical limitations (ie, a Steinbrocker classification score
      of 0 or >= 1), human leukocyte antigen-B27, and antinuclear and rheumatoid
      factors. Disease duration and medication type were also considered. Associations
      between all of these factors and long-term condylar degeneration and MMO were
      assessed by using single and multiple regression analyses. RESULTS: Long-term TMJ
      degeneration and smaller MMO were both associated with younger age at JIA onset
      (P = .01; P = .03) and longer disease duration (P = .05; P = .002). Moreover, MMO
      was negatively associated with physical limitations at intake (P = .04).
      CONCLUSION: Within the limitations of this retrospective study design, these
      results suggest that young JIA patients with early physical limitations and
      prolonged disease are at risk of long-term TMJ degeneration and impaired
      mobility.

PMID- 28437512
TI  - Dentist Practice Patterns and Therapeutic Confidence in the Treatment of Pain
      Related to Temporomandibular Disorders in a Dental Practice-Based Research
      Network.
AB  - AIMS: To quantify the practice patterns of Japanese dentists in the management of
      pain related to temporomandibular disorders (TMD) and to identify specific
      characteristics that are significantly associated with the decision to perform
      occlusal adjustment for TMD-related pain. METHODS: A cross-sectional study was
      conducted consisting of a questionnaire survey of dentists affiliated with the
      Dental Practice-Based Research Network Japan (JDPBRN) (n = 148). Participants
      were asked how they diagnosed and treated TMD-related pain. Associations between
      dentist characteristics and the decision to perform occlusal adjustment were
      analyzed via multiple logistic regression. RESULTS: A total of 113 clinicians
      responded to the questionnaire (76% response rate), and 81% of them (n = 89) had
      treated TMD during the previous year. Dentists treated an average of 1.9 +/- 1.8
      (mean +/- SD) patients with TMD-related pain per month. Most JDPBRN dentists used
      similar diagnostic protocols, including questions and examinations. The most
      frequent treatments were splints or mouthguards (96.5%), medications (84.7%), and
      self-care (69.4%). Occlusal adjustment for TMD-related pain was performed by 58%
      of the participants. Multiple logistic regression analysis identified two factors
      significantly associated with the decision to perform occlusal adjustment:
      dentist lack of confidence in curing TMD-related acute pain (odds ratio [OR]
      5.60; 95% confidence interval [CI] 1.260 to 24.861) and proportion of patients
      with severe TMD-related pain (OR 0.95; 95% CI 0.909 to 0.999). CONCLUSION: The
      most common treatments for TMD-related pain were reversible treatments; however,
      over half of the dentists performed occlusal adjustment for TMD-related pain. The
      results of this study suggest that an evidence-practice gap exists for occlusal
      adjustment for TMD-related pain.

PMID- 28437515
TI  - A New Equation for Predicting Evolution of Oral Pain in Orthodontic Treatment: A
      Longitudinal, Prospective Cohort Study.
AB  - AIMS: To develop an equation capable of relating the evolution of oral pain to
      the time elapsed, measured from the moment of dental archwire fitting and
      identifying when pain begins, peaks, and ends; and secondly, to compare pain
      during orthodontic treatment in relation to archwire material (steel or nickel
      titanium [Ni-Ti]) and position (maxillary or mandibular) and patient age (child,
      teenager, or adult) and gender (male or female). METHODS: A longitudinal
      prospective cohort study was conducted of 112 patients who filled in a scale to
      evaluate pain, noting the times when the pain occurred. The total sample
      consisted of 60 males and 52 females with a mean (+/- standard deviation [SD])
      age of 19.8 +/- 6.2 years. The sample was divided into five groups depending on
      archwire material and position, and patient age and gender. A univariate four-way
      ANOVA model was performed to compare mean pain levels between groups. Bonferroni
      test was used for multiple comparisons. A univariate nonlinear regression model
      was carried out for pain level, 95% confidence intervals (95% CI) were
      calculated, and the statistic R2 was used. RESULTS: An equation was developed
      based on pain levels in relation to time elapsed, measured from the moment when
      the archwire had been fitted in the mouth. The equation had three coefficients
      related to mean pain values: overall pain, peak pain, and how pain decreased. It
      fitted all study groups with a correlation coefficient > 0.9. The model showed
      that pain levels were influenced by archwire material and patient gender and age,
      but not archwire position. CONCLUSION: The equation reproduced the data
      registered and can be applied to studies of pain derived from archwires, and this
      methodology could be used for other external agents fitted in the mouth. Patients
      receiving dental treatment involving external agents can be made aware of the
      pain they can expect to experience. This will enable them to distinguish expected
      pain from other pain, which will help them identify other pathologies requiring
      medical attention and to approach treatment with better motivation since the
      pattern of pain evolution is known in advance.

PMID- 28437516
TI  - A Rare Case of Misdiagnosed Silent Lung Cancer with Solitary Metastasis to the
      Temporomandibular Joint Condyle.
AB  - This article describes the case history of a 59-year-old female patient who
      sought advice for temporomandibular joint (TMJ) pain and sounds but who was
      actually diagnosed with a primary lung cancer with metastasis to the TMJ. The
      patient had a history of TMJ pain and deflection in jaw movement that
      progressively worsened over a few months and did not improve with the usual
      standard of care treatment provided by an orofacial pain practitioner. Magnetic
      resonance and computed tomography (CT) prescribed at a tertiary clinic showed an
      osteolytic bone mass within the right TMJ condyle. The neoformation was
      surgically removed and histologic assessment revealed it was a metastasis of a
      silent lung carcinoma. Thorax CT confirmed the presence of a formation within the
      apical segment of the right lung superior lobe. While this scenario of a silent
      lung cancer metastasis to the TMJ condyle mimicking classical symptoms of
      temporomandibular disorders (TMD) is rare, it does indicate that the path to
      differential diagnosis is often difficult in TMD and orofacial pain patients, and
      that practitioners managing such patients should be aware of the variegate
      spectrum of possible TMD-mimicking conditions to avoid dangerous diagnostic
      delays.

PMID- 28437517
TI  - The Tension Between Promoting Mobility and Preventing Falls in the Hospital.

PMID- 28437518
TI  - A Middle-aged Man With Progressive Ophthalmoparesis, Ataxia, and Spastic
      Paraparesis.
AB  - A 50-year old man presented for evaluation of progressive gait ataxia with a
      superimposed spastic paraparesis. During his clinic visit, he was also observed
      to have slow and limited eye movements. In this article, we discuss the clinical
      approach to this triad of symptoms and guide the reader to discover the patient's
      ultimate genetic diagnosis.

PMID- 28437519
TI  - Consequences of Sibling Death: Problematic, Potentially Predictable, and Poorly
      Managed.

PMID- 28437521
TI  - Home-Based Trials in Adolescent Migraine: A Randomized Clinical Trial.

PMID- 28437520
TI  - Academic Performance, Motor Function, and Behavior 11 Years After Neonatal
      Caffeine Citrate Therapy for Apnea of Prematurity: An 11-Year Follow-up of the
      CAP Randomized Clinical Trial.
AB  - Importance: Caffeine citrate therapy for apnea of prematurity reduces the rates
      of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental
      disability at 18 months and may improve motor function at 5 years. Objective: To
      evaluate whether neonatal caffeine therapy is associated with improved functional
      outcomes 11 years later. Design, Setting, and Participants: A follow-up study was
      conducted at 14 academic hospitals in Canada, Australia, and the United Kingdom
      from May 7, 2011, to May 27, 2016, of English- or French-speaking children who
      had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of
      Prematurity trial between October 11, 1999, and October 22, 2004. A total of 1202
      children with birth weights of 500 to 1250 g were eligible for this study; 920
      (76.5%) had adequate data for the main outcome. Interventions: Caffeine citrate
      or placebo until drug therapy for apnea of prematurity was no longer needed. Main
      Outcomes and Measures: Functional impairment was a composite of poor academic
      performance (defined as at least 1 standard score greater than 2 SD below the
      mean on the Wide Range Achievement Test-4), motor impairment (defined as a
      percentile rank of <=5 on the Movement Assessment Battery for Children-Second
      Edition), and behavior problems (defined as a Total Problem T score >=2 SD above
      the mean on the Child Behavior Checklist). Results: Among the 920 children (444
      females and 476 males; median age, 11.4 years [interquartile range, 11.1-11.8
      years]), the combined rates of functional impairment were not significantly
      different between the 457 children assigned to receive caffeine compared with the
      463 children assigned to receive placebo (145 [31.7%] vs 174 [37.6%]; adjusted
      odds ratio, 0.78; 95% CI, 0.59-1.02; P = .07). With all available data, including
      those from up to 24 Swedish trial participants, the rates of poor academic
      performance on 1 or more of 4 subtests (66 of 458 [14.4%] vs 61 of 462 [13.2%];
      adjusted odds ratio, 1.11; 95% CI, 0.77-1.61; P = .58) and behavior problems (52
      of 476 [10.9%] vs 40 of 481 [8.3%]; adjusted odds ratio, 1.32; 95% CI, 0.85-2.07;
      P = .22) were broadly similar between the group that received caffeine and the
      group that received placebo. However, caffeine therapy was associated with a
      reduced risk of motor impairment compared with placebo (90 of 457 [19.7%] vs 130
      of 473 [27.5%]; adjusted odds ratio, 0.66; 95% CI, 0.48-0.90; P = .009).
      Conclusions and Relevance: Caffeine therapy for apnea of prematurity did not
      significantly reduce the combined rate of academic, motor, and behavioral
      impairments but was associated with a reduced risk of motor impairment in 11-year
      old children with very low birth weight. At the doses used in this trial,
      neonatal caffeine therapy is effective and safe into middle school age. Trial
      Registration: clinicaltrials.gov Identifier: NCT00182312; isrctn.org Identifier:
      ISRCTN44364365.

PMID- 28437522
TI  - Statistical Caution in Big Data Approaches to Transfusion Medicine Research.

PMID- 28437523
TI  - Emergency Department Query for Patient-Centered Approaches to Sexual Orientation
      and Gender Identity : The EQUALITY Study.
AB  - Importance: The Institute of Medicine and The Joint Commission recommend routine
      documentation of patients' sexual orientation in health care settings. Currently,
      very few health care systems collect these data since patient preferences and
      health care professionals' support regarding collection of data about patient
      sexual orientation are unknown. Objective: To identify the optimal patient
      centered approach to collect sexual orientation data in the emergency department
      (ED) in the Emergency Department Query for Patient-Centered Approaches to Sexual
      Orientation and Gender Identity study. Design, Setting, and Participants: An
      exploratory, sequential, mixed-methods design was used first to evaluate
      qualitative interviews conducted in the Baltimore, Maryland, and Washington, DC,
      areas. Fifty-three patients and 26 health care professionals participated in the
      qualitative interviews. Interviews were followed by a national online survey, in
      which 1516 (potential) patients (244 lesbian, 289 gay, 179 bisexual, and 804
      straight) and 429 ED health care professionals (209 physicians and 220 nurses)
      participated. Survey participants were recruited using random digit dialing and
      address-based sampling techniques. Main Outcomes and Measures: Qualitative
      interviews were used to obtain the perspectives of patients and health care
      professionals on sexual orientation data collection, and a quantitative survey
      was used to gauge patients' and health care professionals' willingness to provide
      or obtain sexual orientation information. Results: Mean (SD) age of patient and
      clinician participants was 49 (16.4) and 51 (9.4) years, respectively.
      Qualitative interviews suggested that patients were less likely to refuse to
      provide sexual orientation than providers expected. Nationally, 154 patients
      (10.3%) reported that they would refuse to provide sexual orientation; however,
      333 (77.8%) of all clinicians thought patients would refuse to provide sexual
      orientation. After adjustment for demographic characteristics, only bisexual
      patients had increased odds of refusing to provide sexual orientation compared
      with heterosexual patients (odds ratio, 2.40; 95% CI, 1.26-4.56). Conclusions and
      Relevance: Patients and health care professionals have discordant views on
      routine collection of data on sexual orientation. A minority of patients would
      refuse to provide sexual orientation. Implementation of a standardized, patient
      centered approach for routine collection of sexual orientation data is required
      on a national scale to help to identify and address health disparities among
      lesbian, gay, and bisexual populations.

PMID- 28437524
TI  - The Evolution of the Plateau, an Optical Coherence Tomography Signature Seen in
      Geographic Atrophy.
AB  - Purpose: Histologic details of progression routes to geographic atrophy (GA) in
      AMD are becoming available through optical coherence tomography (OCT). We studied
      the origins and evolution of an OCT signature called plateau in eyes with GA and
      suggested a histologic correlate. Methods: Serial eye-tracked OCT scans and
      multimodal imaging were acquired from eight eyes of seven patients with GA and
      plateau signatures over a mean follow-up of 7.7 years (range, 3.7-11.6). The
      histology of unrelated donor eyes with AMD was reviewed. Results: Drusenoid
      pigment epithelial detachment (PED) on OCT imaging progressed into wide-based
      mound-like signatures with flattened apices characterized by a hyporeflective yet
      heterogeneous interior and an overlying hyperreflective exterior, similar to
      outer retinal corrugations previously ascribed to persistent basal laminar
      deposit (BLamD) but larger. These new signatures are described as "plateaus." An
      initial increase of the PED volume and hyporeflectivity of its contents was
      followed by a decrease in PED volume and thinning of an overlying hyperreflective
      band attributable to the loss of the overlying RPE leaving persistent BLamD. Both
      imaging and histology revealed persistent BLamD with defects through which
      gliotic Muller cell processes pass. Conclusions: Plateaus can be traced back to
      drusenoid PEDs on OCT imaging. We hypothesize that during progressive RPE
      atrophy, Muller cell extension through focal defects in the residual persistent
      BLamD may contribute to the heterogeneous internal reflectivity of these
      entities. The role of Muller cell activation and extension in the pathogenesis of
      AMD should be explored in future studies.

PMID- 28437525
TI  - Visual Impairment, Undercorrected Refractive Errors, and Activity Limitations in
      Older Adults: Findings From the Three-City Alienor Study.
AB  - Purpose: As vision is required in almost all activities of daily living, visual
      impairment (VI) may be one of the major treatable factors for preventing activity
      limitations. We aimed to evaluate the attributable risk of VI associated with
      activity limitations and the extent to which limitations are avoidable with
      optimal optical correction of undercorrected refractive errors. Methods: We
      analyzed 709 older adults from the Three-City-Alienor population-based study. VI
      was defined by presenting distance visual acuity in the better-seeing eye.
      Multivariate modified Poisson regressions were used to estimate the associations
      between vision, activity limitations, and social participation restrictions.
      Population attributable risk (PAR) and generalized impact fraction (GIF) were
      estimated. Bootstrapping was used to estimate 95% confidence intervals (CI).
      Results: After adjustment for potential confounders, VI was associated with each
      domain of activity limitations, except basic activities of daily living (ADL)
      limitations. These associations were found for even minimal levels of VI. PAR was
      estimated at 10.1% (95% CI: 5.2-10.6) for mobility limitations, at 26.0% (95% CI:
      13.5-41.2) for instrumental ADL (IADL) limitations, and at 24.9% (95% CI: 10.5
      47.1) for social participation restrictions. GIF for improvement of
      undercorrected refractive errors was 6.1% (95% CI: 3.8-8.5) for mobility
      limitations, 15.8% (95% CI: 11.5-20.1) for IADL limitations and 21.4% (95% CI:
      13.8-28.5) for social participation restrictions. Conclusions: About one-sixth of
      IADL limitations and one-fifth of social participation restrictions could be
      prevented by an optimal optical correction. These results underline the
      importance of eye examinations in older adults to prevent disability.

PMID- 28437526
TI  - Prominin-1 Is a Novel Regulator of Autophagy in the Human Retinal Pigment
      Epithelium.
AB  - Purpose: Prominin-1 (Prom1) is a transmembrane glycoprotein, which is expressed
      in stem cell lineages, and has recently been implicated in cancer stem cell
      survival. Mutations in the Prom1 gene have been shown to disrupt photoreceptor
      disk morphogenesis and cause an autosomal dominant form of Stargardt-like macular
      dystrophy (STGD4). Despite the apparent structural role of Prom1 in
      photoreceptors, its role in other cells of the retina is unknown. The purpose of
      this study is to investigate the role of Prom1 in the highly metabolically active
      cells of the retinal pigment epithelium (RPE). Methods: Lentiviral siRNA and the
      genome editing CRISPR/Cas9 system were used to knockout Prom1 in primary RPE and
      ARPE-19 cells, respectively. Western blotting, confocal microscopy, and flow
      sight imaging cytometry assays were used to quantify autophagy flux.
      Immunoprecipitation was used to detect Prom1 interacting proteins. Results: Our
      studies demonstrate that Prom1 is primarily a cytosolic protein in the RPE.
      Stress signals and physiological aging robustly increase autophagy with
      concomitant upregulation of Prom1 expression. Knockout of Prom1 increased mTORC1
      and mTORC2 signaling, decreased autophagosome trafficking to the lysosome,
      increased p62 accumulation, and inhibited autophagic puncta induced by activators
      of autophagy. Conversely, ectopic overexpression of Prom1 inhibited mTORC1 and
      mTORC2 activities, and potentiated autophagy flux. Through interactions with p62
      and HDAC6, Prom1 regulates autophagosome maturation and trafficking, suggesting a
      new cytoplasmic role of Prom1 in RPE function. Conclusions: Our results
      demonstrate that Prom1 plays a key role in the regulation of autophagy via
      upstream suppression of mTOR signaling and also acting as a component of a
      macromolecular scaffold involving p62 and HDAC6.

PMID- 28437529
TI  - Incorrect Sample Size in a Table.

PMID- 28437528
TI  - Automated Staging of Age-Related Macular Degeneration Using Optical Coherence
      Tomography.
AB  - Purpose: To evaluate a machine learning algorithm that automatically grades age
      related macular degeneration (AMD) severity stages from optical coherence
      tomography (OCT) scans. Methods: A total of 3265 OCT scans from 1016 patients
      with either no signs of AMD or with signs of early, intermediate, or advanced AMD
      were randomly selected from a large European multicenter database. A machine
      learning system was developed to automatically grade unseen OCT scans into
      different AMD severity stages without requiring retinal layer segmentation. The
      ability of the system to identify high-risk AMD stages and to assign the correct
      severity stage was determined by using receiver operator characteristic (ROC)
      analysis and Cohen's kappa statistics (kappa), respectively. The results were
      compared to those of two human observers. Reproducibility was assessed in an
      independent, publicly available data set of 384 OCT scans. Results: The system
      achieved an area under the ROC curve of 0.980 with a sensitivity of 98.2% at a
      specificity of 91.2%. This compares favorably with the performance of human
      observers who achieved sensitivities of 97.0% and 99.4% at specificities of 89.7%
      and 87.2%, respectively. A good level of agreement with the reference was
      obtained (kappa = 0.713) and was in concordance with the human observers (kappa =
      0.775 and kappa = 0.755, respectively). Conclusions: A machine learning system
      capable of automatically grading OCT scans into AMD severity stages was developed
      and showed similar performance as human observers. The proposed automatic system
      allows for a quick and reliable grading of large quantities of OCT scans, which
      could increase the efficiency of large-scale AMD studies and pave the way for AMD
      screening using OCT.

PMID- 28437530
TI  - Influenza Vaccination in the First Trimester of Pregnancy and Risk of Autism
      Spectrum Disorder-Reply.

PMID- 28437527
TI  - Ocular Motor Nerve Development in the Presence and Absence of Extraocular Muscle.
AB  - Purpose: To spatially and temporally define ocular motor nerve development in the
      presence and absence of extraocular muscles (EOMs). Methods: Myf5cre mice, which
      in the homozygous state lack EOMs, were crossed to an IslMN:GFP reporter line to
      fluorescently label motor neuron cell bodies and axons. Embryonic day (E) 11.5 to
      E15.5 wild-type and Myf5cre/cre:IslMN:GFP whole mount embryos and dissected
      orbits were imaged by confocal microscopy to visualize the developing oculomotor,
      trochlear, and abducens nerves in the presence and absence of EOMs. E11.5 and
      E18.5 brainstems were serially sectioned and stained for Islet1 to determine the
      fate of ocular motor neurons. Results: At E11.5, all three ocular motor nerves in
      mutant embryos approached the orbit with a trajectory similar to that of wild
      type. Subsequently, while wild-type nerves send terminal branches that contact
      target EOMs in a stereotypical pattern, the Myf5cre/cre ocular motor nerves
      failed to form terminal branches, regressed, and by E18.5 two-thirds of their
      corresponding motor neurons died. Comparisons between mutant and wild-type
      embryos revealed novel aspects of trochlear and oculomotor nerve development.
      Conclusions: We delineated mouse ocular motor nerve spatial and temporal
      development in unprecedented detail. Moreover, we found that EOMs are not
      necessary for initial outgrowth and guidance of ocular motor axons from the
      brainstem to the orbit but are required for their terminal branching and
      survival. These data suggest that intermediate targets in the mesenchyme provide
      cues necessary for appropriate targeting of ocular motor axons to the orbit,
      while EOM cues are responsible for terminal branching and motor neuron survival.

PMID- 28437531
TI  - Applicability of the IMPROVE-IT Trial to Current Patients With Acute Coronary
      Syndrome: An NCDR Research to Practice Project.

PMID- 28437532
TI  - The Value of Using Registries to Evaluate Randomized Clinical Trial Study
      Populations.

PMID- 28437533
TI  - Influenza Vaccination in the First Trimester of Pregnancy and Risk of Autism
      Spectrum Disorder.

PMID- 28437534
TI  - Association of Mortality With the Death of a Sibling in Childhood.
AB  - Importance: The death of a close relative is associated with an increased
      mortality risk among the bereaved, but much less is known about the potential
      association of the death of a sibling in childhood with mortality in this
      population. Objective: To examine the association between sibling death in
      childhood and subsequent mortality risk. Design, Setting, and Participants: This
      population-based cohort study of 5 005 029 participants evaluated linked national
      registers in Denmark (January 1, 1973, through December 31, 2009) and Sweden
      (January 1, 1973, through December 31, 2008). A total of 2 060 354 Danish and 2
      944 675 Swedish children who survived the first 6 months of their life were
      included. We excluded 14 children who died of the same external cause as their
      siblings within 30 days. Data were analyzed from November 2, 2015, through
      October 14, 2016. Exposures: Participants were classified as exposed if a sibling
      died in childhood (age <18 years). Main Outcomes and Measures: Poisson regression
      was used to estimate mortality rate ratio (MRR) with the exposure as a time
      varying variable. Results: Among the 55 818 participants who experienced sibling
      death in childhood (51.5% male and 48.5% female; median age at loss, 7.0
      [interquartile range, 3.3-12.1] years), all-cause mortality risk was increased by
      71% (MRR, 1.71; 95% CI, 1.57-1.87) during the follow-up of 37 years. The excess
      mortality risk was observed for groups with specific causes of death, and the
      higher MRRs were found when the sibling pairs died of the same cause (death due
      to disease [MRR, 2.16; 95% CI, 1.87-2.49]; death due to external cause [MRR,
      1.91; 95% CI, 1.54-2.37]). The increased mortality risk after sibling death was
      seen across the follow-up period, regardless of the age at bereavement and the
      type of death among bereaved siblings, but the magnitude of association was
      stronger during the first year after sibling death (MRR, 2.51; 95% CI, 1.79
      3.54). Higher MRRs were found among sibling pairs with the same sex (MRR, 1.92;
      95% CI, 1.70-2.18) and close age (MRR, 1.94; 95% CI, 1.58-2.37). Conclusions and
      Relevance: Bereavement in childhood because of the death of a sibling was
      associated with an increased risk for mortality in the short and long term.
      Health care professionals should be aware of individuals' vulnerability due to
      sibling death, especially for sibling pairs of close age or the same sex. Social
      and health care support may help to minimize the potential adverse effects on the
      bereaved sibling.

PMID- 28437535
TI  - Clinical Aspects of Glucose Transporter Type 1 Deficiency: Information From a
      Global Registry.
AB  - Importance: Case reports regularly document unique or unusual aspects of glucose
      transporter type 1 deficiency (G1D). In contrast, population studies from which
      to draw global inferences are lacking. Twenty-five years after the earliest case
      reports, this deficiency still particularly affects treatment and prognostic
      counseling. Objective: To examine the most common features of G1D. Design,
      Setting, and Participants: In this study, data were collected electronically from
      181 patients with G1D through a web-based, worldwide patient registry from
      December 1, 2013, through December 1, 2016. The study used several statistical
      methods tailored to address the age at onset of various forms of G1D, associated
      manifestations, natural history, treatment efficacy, and diagnostic procedures.
      These factors were correlated in a predictive mathematical model designed to
      guide prognosis on the basis of clinical features present at diagnosis. Results:
      A total of 181 patients with G1D were included in the study (92 [50.8%] male and
      89 female [49.2%]; median age, 9 years; age range, 0-65 years). As previously
      known, a relatively large variety of common phenotypes are characteristic of the
      G1D syndrome, including movement disorders, absence epilepsy (typical and
      atypical), and myoclonic and generalized epilepsies. The 3 main novel results are
      (1) the feasibility of effective dietary therapies (such as the modified Atkins
      diet) other than the ketogenic diet, (2) the relatively frequent occurrence (one
      fourth of cases) of white matter magnetic resonance imaging abnormalities, and
      (3) the favorable effect of early diagnosis and treatment regardless of treatment
      modality and mutation type. In fact, the most important factor that determines
      outcome is age at diagnosis, as reflected in a predictive mathematical model.
      Conclusions and Relevance: The results reveal several changing notions in the
      approach to G1D syndrome diagnosis and treatment, such as the perceived absolute
      requirement for a ketogenic diet, the assumed lack of structural brain defects,
      and the potential existence of genotype-phenotype correlations, all of which are
      contested by the registry data.

PMID- 28437536
TI  - Influenza Vaccination in the First Trimester of Pregnancy and Risk of Autism
      Spectrum Disorder.

PMID- 28437537
TI  - Recent Patterns of Prostate-Specific Antigen Testing for Prostate Cancer
      Screening in the United States.

PMID- 28437538
TI  - Effects of Diagnosis by Newborn Screening for Cystic Fibrosis on Weight and
      Length in the First Year of Life.
AB  - Importance: Since the implementation of universal newborn screening (NBS) for
      cystic fibrosis (CF), the timing and magnitude of growth deficiency or its
      association with correlates of disease among infants with CF who underwent NBS
      has not been well described. Objective: To examine incremental weight gain,
      linear growth, and clinical features in the first year of life among infants with
      CF who underwent NBS. Design, Setting, and Participants: The Baby Observational
      and Nutrition Study (BONUS), a multicenter, longitudinal, observational cohort
      study, was conducted during regular CF clinic visits in the first 12 months of
      life at 28 US Cystic Fibrosis Foundation-accredited Care Centers from January 7,
      2012, through May 31, 2015. Participants included 231 infants younger than 3.5
      months who underwent NBS and had confirmed CF, with a gestational age of at least
      35 weeks, birth weight of at least 2.5 kg, and toleration of full oral feeds. Of
      these, 222 infants (96.1%) had follow-up beyond 6 months of age and 215 (93.1%)
      completed 12 months of follow-up. Exposure: Cystic fibrosis. Main Outcome and
      Measures: Attained weight and length for age and World Health Organization
      normative z scores at ages 1 to 6 and 8, 10, and 12 months (defined a priori).
      Results: Of the 231 infants enrolled, 110 infants (47.6%) were female and 121
      (52.4%) were male, with a mean (SD) age of 2.58 (0.69) months. BONUS infants had
      lower than mean birth weights (mean z score, -0.15; 95% CI, -0.27 to -0.04) and
      higher birth lengths (mean z score, 0.44; 95% CI, 0.26 to 0.62). They achieved
      normal weight by 12 months, a significant improvement over a prescreening cohort
      of newborns with CF from 20 years before the contemporary cohort (mean z score
      increase, 0.57; 95% CI, 0.37-0.77). However, length was lower than the mean at 12
      months (mean z score, -0.56; 95% CI, -0.70 to -0.42). Only 30 infants (13.6%)
      were at less than the 10th percentile of weight for age, whereas 53 (23.9%) were
      at less than the 10th percentile of length for age at more than half their
      visits. Male sex, pancreatic insufficiency, meconium ileus, histamine blocker
      use, and respiratory Pseudomonas aeruginosa infection were associated with lower
      weight or length during the first year. Insulinlike growth factor 1 levels were
      significantly lower among low-length infants. Persistently low-weight infants
      consumed significantly more calories, and weight and length z scores were
      negatively correlated with caloric intake. Conclusions and Relevance: Since
      initiation of universal NBS for CF, significant improvement has occurred in
      nutritional status, with normalization of weight in the first year of life.
      However, length stunting remains common.

PMID- 28437541
TI  - Time for an End to Juice in the Special Supplemental Nutrition Program for Women,
      Infants, and Children.

PMID- 28437539
TI  - Safety and Efficacy of Antiviral Therapy for Prevention of Cytomegalovirus
      Reactivation in Immunocompetent Critically Ill Patients: A Randomized Clinical
      Trial.
AB  - Importance: Latent cytomegalovirus (CMV) infection is present in more than half
      the adult population, and a viral reactivation (ie, when the virus becomes
      measurable in body fluids such as blood) can occur in up to one-third of these
      individuals during episodes of critical illness. Objective: To determine whether
      antiviral therapy is safe and effective for preventing CMV reactivation in a
      general population of critically ill patients. Design, Setting, and Participants:
      A single-center, open-label, randomized, controlled clinical trial recruited 124
      CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours
      in the intensive care unit between January 1, 2012, and January 31, 2014. The
      mean baseline Acute Physiology and Chronic Health Evaluation II score of all
      patients was 17.6. Interventions: Patients were randomized to receive anti-CMV
      prophylaxis with valacyclovir hydrochloride (n = 34) or low-dose valganciclovir
      hydrochloride (n = 46) for up to 28 days to suppress viral reactivation, or to a
      control group with no intervention (n = 44). Main Outcomes and Measures: Time to
      first CMV reactivation in blood within the 28-day follow-up period following
      initiation of the study drug. Results: Among the 124 patients in the study (46
      women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the
      blood occurred in 12 patients in the control group, compared with 1 patient in
      the valganciclovir group and 2 patients in the valacyclovir group (combined
      treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this
      trial was not powered to assess clinical end points, the valacyclovir arm was
      halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had
      died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the
      point of the decision to halt this arm. Other safety end points showed similar
      outcomes between groups. Conclusions and Relevance: Antiviral prophylaxis with
      valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients
      with critical illness. However, given the higher mortality, a large-scale trial
      would be needed to determine the clinical efficacy and safety of CMV suppression.
      Trial Registration: clinicaltrials.gov Identifier: NCT01503918.

PMID- 28437542
TI  - Challenges to Translation and the Hippocratic Oath by Premature Termination of
      Spinal Cord Stem Cell-Based Trials.

PMID- 28437540
TI  - Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis
      Monocytes.
AB  - Importance: Amyotrophic lateral sclerosis (ALS) is a common adult-onset
      neurodegenerative disease characterized by selective loss of upper and lower
      motor neurons. Patients with ALS have persistent peripheral and central
      inflammatory responses including abnormally functioning T cells and activated
      microglia. However, much less is known about the inflammatory gene profile of
      circulating innate immune monocytes in these patients. Objective: To characterize
      the transcriptomics of peripheral monocytes in patients with ALS. Design,
      Setting, and Participants: Monocytes were isolated from peripheral blood of 43
      patients with ALS and 22 healthy control individuals. Total RNA was extracted
      from the monocytes and subjected to deep RNA sequencing, and these results were
      validated by quantitative reverse transcription polymerase chain reaction. Main
      Outcomes and Measures: The differential expressed gene signatures of these
      monocytes were identified using unbiased RNA sequencing strategy for gene
      expression profiling. Results: The demographics between the patients with ALS
      (mean [SD] age, 58.8 [1.57] years; 55.8% were men and 44.2% were women; 90.7%
      were white, 4.65% were Hispanic, 2.33% were black, and 2.33% were Asian) and
      control individuals were similar (mean [SD] age, 57.6 [2.15] years; 50.0% were
      men and 50.0% were women; 90.9% were white, none were Hispanic, none were black,
      and 9.09% were Asian). RNA sequencing data from negative selected monocytes
      revealed 233 differential expressed genes in ALS monocytes compared with healthy
      control monocytes. Notably, ALS monocytes demonstrated a unique inflammation
      related gene expression profile, the most prominent of which, including IL1B,
      IL8, FOSB, CXCL1, and CXCL2, were confirmed by quantitative reverse transcription
      polymerase chain reaction (IL8, mean [SE], 1.00 [0.18]; P = .002; FOSB, 1.00
      [0.21]; P = .009; CXCL1, 1.00 [0.14]; P = .002; and CXCL2, 1.00 [0.11]; P = .01).
      Amyotrophic lateral sclerosis monocytes from rapidly progressing patients had
      more proinflammatory DEGs than monocytes from slowly progressing patients.
      Conclusions and Relevance: Our data indicate that ALS monocytes are skewed toward
      a proinflammatory state in the peripheral circulation and may play a role in ALS
      disease progression, especially in rapidly progressing patients. This increased
      inflammatory response of peripheral immune cells may provide a potential target
      for disease-modifying therapy in patients with ALS.

PMID- 28437544
TI  - Polypharmacy in the Elderly-When Good Drugs Lead to Bad Outcomes: A Teachable
      Moment.

PMID- 28437543
TI  - Association of Donor Age and Sex With Survival of Patients Receiving
      Transfusions.
AB  - Importance: Following animal model data indicating the possible rejuvenating
      effects of blood from young donors, there have been at least 2 observational
      studies conducted with humans that have investigated whether donor age affects
      patient outcomes. Results, however, have been conflicting. Objective: To study
      the association of donor age and sex with survival of patients receiving
      transfusions. Design, Setting, and Participants: A retrospective cohort study
      based on the Scandinavian Donations and Transfusions database, with nationwide
      data, was conducted for all patients from Sweden and Denmark who received at
      least 1 red blood cell transfusion of autologous blood or blood from unknown
      donors between January 1, 2003, and December 31, 2012. Patients were followed up
      from the first transfusion until death, emigration, or end of follow-up. Data
      analysis was performed from September 15 to November 15, 2016. Exposures: The
      number of transfusions from blood donors of different age and sex. Exposure was
      treated time dependently throughout follow-up. Main Outcomes and Measures: Hazard
      ratios (HRs) for death and adjusted cumulative mortality differences, both
      estimated using Cox proportional hazards regression. Results: Results of a crude
      analysis including 968 264 transfusion recipients (550 257 women and 418 007 men;
      median age at first transfusion, 73.0 years [interquartile range, 59.8-82.4
      years]) showed a U-shaped association between age of the blood donor and
      recipient mortality, with a nadir in recipients for the most common donor age
      group (40-49 years) and significant and increasing HRs among recipients of blood
      from donors of successively more extreme age groups (<20 years: HR, 1.12; 95% CI,
      1.10-1.14; >=70 years: HR, 1.25; 95% CI, 1.08-1.44). Higher mortality was also
      noted among recipients of blood from female donors (HR, 1.07; 95% CI, 1.07-1.07).
      Adjustments for number of transfusions with a linear term attenuated the
      associations, but the increased mortality for recipients of blood from young,
      old, and female donors was not eliminated. Closer examination of the association
      between number of transfusions and mortality revealed a nonlinear pattern. After
      adjustments to accommodate nonlinearity, donor age and sex were no longer
      associated with patient mortality. Conclusions and Relevance: Donor age and sex
      were not associated with patient survival and need not be considered in blood
      allocation. Any comparison between common and less common categories of
      transfusions will inevitably be confounded by the number of transfusions, which
      drives the probability of receiving the less common blood components. Previous
      positive findings regarding donor age and sex are most likely explained by
      residual confounding.

PMID- 28437545
TI  - Union, Knee Alignment, and Clinical Outcomes of Patients Treated With Autologous
      Bone Grafting for Medial Tibial Defects in Primary Total Knee Arthroplasty.
AB  - Autologous bone grafting is an established method to overcome bone deficiencies
      in primary total knee arthroplasty (TKA). However, recently, metal augments have
      been used by many surgeons. Although autologous bone grafting is a common
      technique, few large studies have described its success in achieving bone union
      in primary TKA. The goal of this study was to evaluate primary TKA with
      autologous bone grafting for tibial defects. A total of 68 knees that had
      undergone arthroplasty with autologous bone grafting with more than 1 year of
      follow-up were evaluated. Average follow-up was 6.6 years (range, 1.2-14.6
      years). The autologous bone grafting procedure attached the proximal portion of
      the tibial resection from the lateral side to the bone graft on the medial side
      with 2 screws. The prosthesis, which had a standard and nonrevision stem, was
      implanted with cement. Bone union was assessed with fluoroscopic radiography with
      a weight-bearing anteroposterior view. The rate of bone union was 97% (65 knees).
      Correction of preoperative alignment was achieved and maintained until final
      follow-up. Postoperative knee angle and knee and function scores showed
      significant improvement. One infection occurred, but there were no local
      complications, such as backout of screws or collapse of bone grafts. The authors
      believe that autologous bone graft within TKA is a relatively simple and
      effective procedure that provides good bone union. [Orthopedics. 2017; 40(4):e604
      e608.].

PMID- 28437546
TI  - Root Cause Analysis and Actions for the Prevention of Medical Errors: Quality
      Improvement and Resident Education.
AB  - The quality of care delivered by orthopedic surgeons continues to grow in
      importance. Multiple orthopedic programs, organizations, and committees have been
      created to measure the quality of surgical care and reduce the incidence of
      medical adverse events. Structured root cause analysis and actions (RCA2) has
      become an area of interest. If performed thoroughly, RCA2 has been shown to
      reduce surgical errors across many subspecialties. The Accreditation Council for
      Graduate Medical Education has a new mandate for programs to involve residents in
      quality improvement processes. Resident engagement in the RCA2 process has the
      dual benefit of educating trainees in patient safety and producing meaningful
      changes to patient care that may not occur with traditional quality improvement
      initiatives. The RCA2 process described in this article can provide a model for
      the development of quality improvement programs. In this article, the authors
      discuss the history and methods of the RCA2 process, provide a stepwise approach,
      and give a case example. [Orthopedics. 2017; 40(4):e628-e635.].

PMID- 28437547
TI  - Concordance of Patient and Physician Perceptions of Care in an Orthopedic Clinic.
AB  - It is essential to study whether physicians' perceptions align with their
      patients' views, as understanding patient perception leads to superior
      satisfaction and health outcomes. Previous studies have established differences
      in physician-patient perceptions, but no studies have been conducted in
      orthopedic clinics. The authors' primary goal was to evaluate differences in
      physician and patient perceptions of an orthopedic clinic visit. Their secondary
      objective was to determine the influence of visit length, demographics, and
      depression risk-level on patient satisfaction. The authors surveyed 143 new
      patients being seen by orthopedic surgeons at a level I trauma center. After
      their appointment, these patients completed surveys on satisfaction and
      likelihood of depression. The authors recorded wait times and visit lengths.
      Simultaneously, the physicians completed a self-evaluative satisfaction survey.
      Patients' and physicians' answers were compared using a Wilcoxon signed-rank
      test. Mann-Whitney and Spearman correlation analyses were used to assess factors
      that impact satisfaction. Physicians and patients showed no significant
      differences on most questions of the satisfaction survey, except that physicians
      reported feeling less satisfied with their own explanations (P<.001). Length of
      visit was positively correlated with patient satisfaction (R=0.276, P=.001),
      while waiting times had no effect. Patients at risk for depression were less
      satisfied with physicians' effort to include them in decision-making (P=.044).
      Age was a predictor of greater satisfaction with explanations (P=.032) and
      instructions (P=.009) from the physician. Thus, orthopedic clinics may not
      exhibit the same physician-patient perception patterns as primary care clinics,
      potentially because of differences in patient populations, conditions, or
      expectations. [Orthopedics. 2017; 40(4):242-246.].

PMID- 28437548
TI  - Arthroscopic Treatment of a Displaced Nonunion of the Anterior Inferior Iliac
      Spine Causing Extra-articular Impingement.
AB  - This report describes a case of nonunion of an anterior inferior iliac spine
      (AIIS) apophyseal avulsion fracture with resultant subspine impingement combined
      with symptomatic femoroacetabular impingement (FAI). A 16-year-old male soccer
      player presented with a 6-month history of right groin pain exacerbated by
      kicking and running. The patient was diagnosed with a displaced nonunion of the
      AIIS apophysis avulsion fracture causing secondary extra-articular impingement
      beyond cam-type FAI by physical examination and radiological findings. The
      authors performed arthroscopic AIIS decompression, with concurrent FAI correction
      and labral repair and capsular closure. At 4 months after surgery, a radiograph
      and a computed tomography scan showed complete bony union of the AIIS apophyseal
      nonunion. Modified Harris Hip Sore and Nonarthritic Hip Score improved from 74.8
      and 61, respectively, to 100 for both at final follow-up. The effectiveness of
      arthroscopic decompression of the AIIS as part of a comprehensive minimally
      invasive surgery including FAI correction and labral repair resulted in complete
      union of the AIIS and pain-free return to sport and bony union. [Orthopedics.
      2017; 40(4):e725-e728.].

PMID- 28437549
TI  - Poor Utility of Gonadal Shielding for Pediatric Pelvic Radiographs.
AB  - Plain pelvic radiographs are commonly used for a variety of pediatric orthopedic
      disorders. Lead shielding is typically placed over the gonads to minimize
      radiation exposure to these sensitive tissues. However, misplaced shielding can
      sabotage efforts to protect patients from excessive radiation exposure either by
      not covering radiosensitive tissues or by obscuring anatomic areas of interest,
      prompting repeat radiographic examinations. The goal of this study was to
      determine the incidence of misplaced shielding for pelvic radiographs obtained
      for pediatric orthopedic evaluation. Children 8 to 16 years old who had an
      anteroposterior or frog lateral pelvic radiograph between 2008 and 2014 were
      included. A total of 3400 patients met the inclusion criteria, and 84 boys and 84
      girls were randomly selected for review. For both boys and girls, the percentage
      of incorrectly positioned or missing shields was calculated. Chi-square testing
      was used to compare the frequency of missing or incorrectly placed shields
      between sexes and age groups. Pelvic shields were misplaced in 49% of
      anteroposterior and 63% of frog lateral radiographs. Shielding was misplaced more
      frequently for girls than for boys on frog lateral radiographs (76% vs 51%;
      P<.05). Pelvic bony landmarks were often obscured by pelvic shielding, with a
      frequency of 7% to 43%, depending on the specific landmark. The femoral head and
      acetabulum were obscured by shielding in up to 2% of all images. The findings
      suggest that accepted pelvic shielding protocols are ineffective. Consideration
      should be given to alternative protocols or abandonment of this practice.
      [Orthopedics. 2017; 40(4):e623-e627.].

PMID- 28437550
TI  - Use of Magnetic Resonance Imaging to Predict Quadrupled Semitendinosus Graft
      Diameter in All-Inside Anterior Cruciate Ligament Reconstruction.
AB  - This study was conducted to evaluate whether preoperative magnetic resonance
      imaging (MRI) measurements of the cross-sectional area and length of the
      semitendinosus tendon correlated with graft diameter. The goal of the study was
      to identify tendons at risk for requiring graft augmentation. The records of 140
      consecutive patients undergoing anterior cruciate ligament (ACL) reconstruction
      between 2013 and 2016 were examined retrospectively. The study included 39
      patients who underwent all-inside ACL reconstruction with a semitendinosus
      autograft. A single researcher used preoperative MRI scans to measure the cross
      sectional area and length of the semitendinosus tendon. Graft cross-sectional
      area was correlated with semitendinosus tendon cross-sectional area with Pear
      son's coefficients of 0.50 (95% confidence interval [CI], 0.21-0.70; P=.0013) and
      0.59 (95% CI, 0.34-0.76; P=.0001) when measured under 2* and 4* magnification,
      respectively. In addition, MRI measurements of semitendinosus tendon length were
      correlated with both intraoperatively measured tendon length (r=0.75; 95% CI,
      0.40-0.91; P=.0008) and graft diameter (r=0.43; 95% CI, 0.14-0.66; P=.0058).
      Average semitendinosus tendon cross-sectional area was 3.10 mm2 (95% CI, 0.53
      5.67; P=.024) greater and semitendinosus tendon length was 14.05 mm (95% CI, 1.25
      26.85; P=.035) greater in cases that did not require graft augmentation.
      Semitendinosus tendons with cross-sectional area of less than 13.2 mm2 or length
      of less than 81 mm are most likely to require graft augmentation. In addition,
      MRI measurements of the length and cross-sectional area of the semitendinosus
      tendon are significantly correlated with ACL graft diameter and could help to
      identify patients who may require graft augmentation. [Orthopedics. 2017;
      40(4):e617-e622.].

PMID- 28437551
TI  - Association of interleukin-6 gene polymorphisms and circulating levels with
      keloid scars in a Chinese Han population.
AB  - The aim of the present study is to explore the effect of IL-6 gene polymorphisms
      on the development of keloid scar (KS) in the Chinese Han population. Genotyping
      of IL-6 was performed by the polymerase chain reaction (PCR), followed by
      restriction fragment length polymorphism assays (PCR-RFLP). Serum level of IL-6
      was measured using enzyme-linked immunosorbent assay (ELISA). Results indicated
      that when the IL-6 -572 CC homozygote genotype was used as the reference group,
      the GG genotype was found to be associated with a significantly increased risk of
      KS (GG vs CC: OR = 2.097, 95%CI  = 1.100-3.995, P  =  0.025). When the IL-6 -572
      C allele was used as the reference group, the G allele was found to be associated
      with significantly increased risk of KS (G vs C: OR =  1.317, 95%CI  = 1.002
      1.730, P = 0.048). Furthermore, we observed a marked increase in serum IL-6
      levels in KS patients with GG genotypes when compared to KS patients harboring
      the CC genotype. In conclusion, our results suggest that IL-6 gene polymorphism
      was associated with keloid scars in the southeastern Chinese Han population.

PMID- 28437552
TI  - BCR-ABL1 transcript types showed distinct laboratory characteristics in patients
      with chronic myeloid leukemia.
AB  - In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and
      e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting
      results, the clinical value of these transcripts remains controversial. The aim
      of this study was to identify associations of e14a2 and e13a2 transcripts with
      laboratory variables and also the response to treatment. This study included 203
      adult patients with CML treated with Imatinib as first-line drug in a reference
      hematology center in Northeast Brazil. Clinical and laboratory data were obtained
      after informed consent. Samples were collected for RNA extraction and analyzed by
      reverse transcription-polymerase chain reaction (PCR), according to the
      international protocol BIOMED-1. The LeukemiaNet 2013 criteria were used to
      establish the molecular response. The frequency distribution of the BCR-ABL1
      transcripts was e14a2 (64%), e13a2 (34%), and double positives (2%). The results
      showed a statistically significant association of the e14a2 transcript type with
      thrombocytosis (P = 0.0005) and the e13a2 with higher leukocyte count (P =
      0.0491). In a subgroup of 44 patients, the molecular response to treatment with
      Imatinib was assessed by quantitative PCR at 3 months (BCR-ABL1 <= 10%), 6 months
      (BCR-ABL1 <= 1%), or 12 months (BCR-ABL1 <= 0.1%). Although patients with the
      transcript e14a2 showed higher frequency of good responses than patients with the
      transcript e13a2, this difference was not statistically significant. In agreement
      with published data, our results showed association of the BCR-ABL1 transcript
      e14a2 with thrombocytosis and the BCR-ABL1 transcript e13a2 with higher
      leukocytosis in patients with chronic myeloid leukemia.

PMID- 28437553
TI  - Genotype x environment interaction on experimental hybrids of chili pepper.
AB  - In Brazil, cultivation of hybrid plants comprise near 40% of the area grown with
      vegetables. For Capsicum, hybrids of bell and chili peppers have already exceeded
      50% and over 25% of all are commercialized seeds. This study aimed to evaluate
      new pepper hybrids in two environments, Caceres, MT, and Campos dos Goytacazes,
      RJ, Brazil. Nine experimental hybrids of C. baccatum var. pendulum were tested
      and trials were performed in a randomized block design, with three replications
      and eight plants per plot. In each environment, plants were assessed for canopy
      diameter, plant height, number of fruit per plant, mean fruit mass per plant,
      fruit length and diameter, pulp thickness, and content of soluble solids. Seven
      of the eight traits have differed significantly due to environment variation.
      Furthermore, genotype and environment interaction was highly significant for
      number of fruit per plant, mean fruit mass per plant, fruit length, and fruit
      diameter. Choosing a hybrid to be grown in one of the studied locations must be
      in accordance with the sought characteristics since there is a complex
      interaction for some studied traits.

PMID- 28437554
TI  - Molecular identification of cetaceans from the West Atlantic using the E3-I5
      region of COI.
AB  - Molecular identification is very useful in cases where morphology-based species
      identification is not possible. Examples for its application in cetaceans include
      the identification of carcasses of stranded animals in advanced state of
      decomposition and body parts that are illegally traded. One DNA region that is
      often used for molecular identification is the Folmer region of the mitochondrial
      gene cytochrome c oxidase subunit I (COI) (locus 48 to 705 bp). This locus has
      been used for the identification of several animal species, including whales and
      dolphins. The goal of the present study was to evaluate the usefulness of another
      region of COI, the E3-I5 (locus 685 to locus 1179; 495 bp) as a marker for
      identification of cetaceans from northeastern Canada and northeastern Brazil. The
      identification markers were successfully obtained for seven cetacean species
      after performing percent identity and Basic Local Alignment Search Tool analyses.
      The obtained markers are now publicly available and are useful for the
      identification of the endangered blue whale (Balaenoptera musculus), common minke
      whale (B. acutorostrata), vulnerable sperm whale (Physeter macrocephalus), harbor
      porpoise (Phocoena phocoena), common bottlenose dolphin (Tursiops truncatus),
      Guiana dolphin (Sotalia guianensis), and melon-headed whale (Peponocephala
      electra).

PMID- 28437555
TI  - Polymorphisms of AluI and Hin1I loci of the IGF-1R gene and their genetic effects
      on growth traits in Bian chickens.
AB  - Growth traits are important economic traits in broiler chicken production. AluI
      and Hin1I loci are two restriction sites, which are respectively located in exons
      2 and 3 of the IGF-1R gene. These two loci are significantly related to the
      growth traits in Jinghai Yellow chickens. In this study, a correlation analysis
      was performed between these two loci and the growth traits of Bian chickens. The
      results showed a G376A mutation at the AluI site and a C919A mutation at the
      Hin1I site, which respectively resulted in three genotypes AA, AB, and BB in exon
      2 and three genotypes CC, CD, and DD in exon 3. Correlation analysis showed that
      the female Bian chickens with the AA genotype of the AluI locus had higher body
      weights than those with the AB genotype (P < 0.05) at 8, 14, 16, and 18 weeks;
      individuals with CD genotype of Hin1I locus had higher body weights at 6, 8, 10,
      12, and 14 weeks compared to the CC genotype (P < 0.05 or P < 0.01). Combined
      genotypes analysis showed that at the age of 8, 14, 16, and 18 weeks, the body
      weight of AACC genotype combination was higher than that of the ABCC genotype
      combination (P < 0.05); at the age of 6, 8, 12, 14, 16, and 18 weeks, the AACD
      genotype combination had higher (P < 0.05 or P < 0.01) body weight than that of
      the ABCC genotype.

PMID- 28437556
TI  - Inheritance of bacterial spot resistance in Capsicum annuum var. annuum.
AB  - Since 2008, Brazil is the largest consumer of agrochemicals, which increases
      production costs and risks of agricultural products, environment, and farmers'
      contamination. Sweet pepper, which is one of the main consumed vegetables in the
      country, is on top of the list of the most sprayed crops. The bacterial spot,
      caused by Xanthomonas spp, is one of the most damaging diseases of pepper crops.
      Genetic resistant consists of a suitable way of disease control, but development
      of durable resistant cultivars as well as understanding of plant-bacterium
      interaction is being a challenge for plant breeders and pathologists worldwide.
      Inheritance of disease resistance is often variable, depending on genetic
      background of the parents. The knowledge of the genetic base controlling such
      resistance is the first step in a breeding program aiming to develop new
      genotypes, bringing together resistance and other superior agronomic traits. This
      study reports the genetic basis of bacterial spot resistance in Capsicum annuum
      var. annuum using mean generation analysis from crosses between accessions UENF
      2285 (susceptible) and UENF 1381 (resistant). The plants of each generation were
      grown in a greenhouse and leaflets were inoculated with bacterial strain ENA 4135
      at 105 CFU/mL in 1.0 cm2 of the mesophyll. Evaluations were performed using a
      scoring scale whose grades ranged from 1.0 (resistant) to 5.0 (susceptible),
      depending on symptom manifestation. Genetic control of bacterial spot has a
      quantitative aspect, with higher additive effect. The quantitative analysis
      showed that five genes were the minimum number controlling bacterial spot
      resistance. Additive effect was higher (6.06) than dominant (3.31) and explained
      86.36% of total variation.

PMID- 28437557
TI  - Expression of catalase, alcohol dehydrogenase, and malate dehydrogenase in rot
      grains upon fungicide use on maize hybrids grown at different spacings.
AB  - In this study, we evaluated the fungicide effect on the incidence of rot grains
      and expression of catalase (CAT), alcohol dehydrogenase (ADH), and malate
      dehydrogenase (MDH) enzymes in commercial maize hybrids grown with conventional
      and reduced spacing in Guarapuava, PR, Brazil. The experiment was designed in
      random blocks with a 3 * 8-factorial scheme, totaling 24 treatments. The first
      factor constituted three levels, the first with foliar fungicide application
      [150.0 g/L trifloxystrobin (15.0%, w/v) + 175.0 g/L prothioconazole (17.5%, w/v)]
      at a dose of 0.4 L/ha at V8-stage eight expanded leaves and the second with an
      application of 0.5 L/ha at VT-tasseling and check (no fungicide application)
      stage. The second factor comprised eight maize hybrids that were divided into two
      groups, complex (AG 9045PRO, AG 8041PRO, DKB245PRO2, and 2B707PW) and susceptible
      (P 32R48H, DKB390PRO, P 30F53H, and P 30R50H), according to their reaction to the
      causative fungus, totaling 72 plots at each site in the crop of 2013/2014. The
      percentage of rot grains and the expression of CAT, ADH, and MDH were evaluated
      for each hybrid. The percentage of rot grains was influenced by the hybrid and
      fungicide used. The (trifloxystrobin + prothioconazole) reduced the incidence of
      rot grains, with relatively higher reduction in the hybrids considered
      susceptible. The higher expression of CAT enzyme was related to the higher
      incidence of rot grains because of grain deterioration, depending on the hybrids
      evaluated. A higher expression of ADH and MDH enzymes was observed in the maize
      hybrids belonging to the group considered tolerant.

PMID- 28437558
TI  - Genetic diversity of Bromeliaceae species from the Atlantic Forest.
AB  - The Bromeliaceae family includes a range of species used for many purposes,
      including ornamental use and use as food, medicine, feed, and fiber. The state of
      Espirito Santo, Brazil is a center of diversity for this family in the Atlantic
      Forest. We evaluated the genetic diversity of five populations of the
      Bromeliaceae family, including specimens of the genera Aechmea, Billbergia
      (subfamily Bromelioideae), and Pitcairnia (subfamily Pitcairnioidea), all found
      in the Atlantic Forest and distributed in the state of Espirito Santo. The number
      of alleles per locus in populations ranged from two to six and the fixation index
      (F), estimated for some simple sequence repeats in bromeliad populations, was
      less than zero in all populations. All markers in the Pitcairnia flammea
      population were in Hardy-Weinberg equilibrium (P < 0.05). Moreover, significant
      deviations from Hardy-Weinberg equilibrium were observed at some loci in
      populations of the five bromeliad species. In most cases, this can be attributed
      to the presence of inbreeding or the Wahlund effect. The genetic diversity
      indices of five species showed greater allelic richness in P. flammea (3.55).
      Therefore, we provide useful information for the characterization of genetic
      diversity in natural populations of Aechmea ramosa, Aechmea nudicaulis,
      Billbergia horrid, Billbergia euphemia, and P. flammea in Atlantic Forest
      remnants in the south of Espirito Santo state.

PMID- 28437559
TI  - Chromosomal evolution in large pelagic oceanic apex predators, the barracudas
      (Sphyraenidae, Percomorpha).
AB  - Sphyraena (barracudas) represents the only genus of the Sphyraenidae family and
      includes 27 species distributed into the tropical and subtropical oceanic
      regions. These pelagic predators can reach large sizes and, thus, attracting
      significant interest from commercial and sport fishing. Evolutionary data for
      this fish group, as well its chromosomal patterns, are very incipient. In the
      present study, the species Sphyraena guachancho, S. barracuda, and S. picudilla
      were analyzed under conventional (Giemsa staining, C-banding, and Ag-NOR) and
      molecular (CMA3 banding, and in situ hybridization with 18S rDNA, 5S rDNA, and
      telomeric probes) cytogenetic methods. The karyotypic patterns contrast with the
      current phylogenetic relationships proposed for this group, showing by themselves
      to be distinct among closely related species, and similar among less related
      ones. This indicates homoplasic characteristics, with similar karyotype patterns
      originating at least twice, independently. Although still cytogenetically poor
      investigated, our data were enough to put in evidence a variety of ancient
      conserved traits and evolutionary novelties for the Sphyraena genus. In this
      sense, it is fundamental that a larger number of Sphyraenidae species, as well as
      of other phylogenetically related families, be also investigated. This will
      solidify the knowledge of their karyotypic patterns, and the evolutionary path
      followed by the species of this particular fish family.

PMID- 28437560
TI  - Phylogeography and population structure analysis reveals diversity by mutations
      in Lasiodiplodia theobromae with distinct sources of selection.
AB  - Lasiodiplodia theobromae is a plant pathogen with a worldwide distribution, with
      low host specificity, causing stem cankers, dieback diseases, and fruit rot in
      several species of plants. In coconut, this pathogen is reported as the
      etiological agent of "coconut leaf blight" (CLB) disease, causing several losses
      in fruit production. The CLB is an important disease for this crop in Brazil. In
      our study, we used a phylogeographic approach through the molecular
      characterization of the translation elongation factor 1-alpha (TEF1-alpha) to
      elucidate the pathogen distribution in Brazil and other countries, besides,
      search information about diversity sources of this pathogen in coconut palm tree
      at Brazilian northern, northeast, and southeast. We found that L. theobromae
      diversity is within populations (locations), and populations that are located
      closest to the center of the tropical zone have more variability as Central
      Africa, Brazilian Southeast, and Northeast. The widespread distribution could be
      in part related with long-distance dispersal via global trade of plants and plant
      products. The entrance route of L. theobromae in Brazil probably occurred from
      Africa route and not occurred once. In Brazil, the diversity of this pathogen in
      coconut tree could be linked to two agents of selection: high host diversity (in
      Northeast) and distinct management measures adopted in Southeast. These different
      sources of selection, mainly the mutations, could be one of the reasons that we
      found distinct reactions to "coconut leaf blight" chemical control in these
      regions.

PMID- 28437561
TI  - Semiparametric probit models with univariate and bivariate current-status data.
AB  - Multivariate current-status data are frequently encountered in biomedical and
      public health studies. Semiparametric regression models have been extensively
      studied for univariate current-status data, but most existing estimation
      procedures are computationally intensive, involving either penalization or
      smoothing techniques. It becomes more challenging for the analysis of
      multivariate current-status data. In this article, we study the maximum
      likelihood estimations for univariate and bivariate current-status data under the
      semiparametric probit regression models. We present a simple computational
      procedure combining the expectation-maximization algorithm with the pool-adjacent
      violators algorithm for solving the monotone constraint on the baseline function.
      Asymptotic properties of the maximum likelihood estimators are investigated,
      including the calculation of the explicit information bound for univariate
      current-status data, as well as the asymptotic consistency and convergence rate
      for bivariate current-status data. Extensive simulation studies showed that the
      proposed computational procedures performed well under small or moderate sample
      sizes. We demonstrate the estimation procedure with two real data examples in the
      areas of diabetic and HIV research.

PMID- 28437562
TI  - No postcopulatory selection against MHC-homozygous offspring: Evidence from a
      pedigreed captive rhesus macaque colony.
AB  - The heterozygosity status of polymorphic elements of the immune system, such as
      the major histocompatibility complex (MHC), is known to increase the potential to
      cope with a wider variety of pathogens. Pre- and postcopulatory processes may
      regulate MHC heterozygosity. In a population where mating occurs among
      individuals that share identical MHC haplotypes, postcopulatory selection may
      disfavour homozygous offspring or ones with two MHC haplotypes identical to its
      mother. We tested these ideas by determining the incidence of MHC-heterozygous
      and MHC-homozygous individuals in a pedigreed, partially consanguineous captive
      rhesus monkey colony. Bayesian statistics showed that when parents share MHC
      haplotypes, the distribution of MHC-heterozygous and MHC-homozygous individuals
      significantly fitted the expected Mendelian distribution, both for the complete
      MHC haplotypes, and for MHC class I or II genes separately. Altogether, we found
      in this captive colony no evidence for postcopulatory selection against MHC
      homozygous individuals. However, the distribution of paternally and maternally
      inherited MHC haplotypes tended to differ significantly from expected.
      Individuals with two MHC haplotypes identical to their mother were
      underrepresented and offspring with MHC haplotypes identical to their father
      tended to be overrepresented. This suggests that postcopulatory processes affect
      MHC haplotype combination in offspring, but do not prevent low MHC
      heterozygosity.

PMID- 28437563
TI  - Selective imaging modalities after first pyelonephritis failed to identify
      significant urological anomalies, despite normal antenatal ultrasounds.
AB  - AIM: We investigated the consequences of applying different imaging guidelines
      for urological anomalies after first pyelonephritis in children with normal
      routine antenatal ultrasounds. METHODS: The cohort comprised 472 children treated
      for their first culture-positive pyelonephritis and investigated with ultrasound
      and renal scintigraphy. We excluded patients with known urological anomalies and
      patients born before routine antenatal ultrasound. We followed the cohort for a
      median of 5.7 years (3.1-10.1 years) by reviewing their medical reports. RESULTS:
      Urological anomalies were diagnosed in 95 patients. Dilated vesicoureteral reflux
      (VUR) was the predominant finding (n = 29), including nine who initially had
      surgery. Using imaging guidelines from the American Academy of Pediatrics would
      have missed 11 urological patients, including two with initial surgery, and
      avoided 339 scintigraphies. Using the European Association of Paediatric Urology
      guidance would have missed three urological patients, one with initial surgery,
      and avoided 46 scintigraphies. Investigating patients under two years with
      ultrasound and scintigraphy, and just ultrasound in children over two years,
      would have identified all patients initially treated with surgery and avoided 65
      scintigraphies. CONCLUSION: Dilated VUR was the dominant anomaly in a cohort with
      first time pyelonephritis and normal antenatal ultrasound. The optimal imaging
      strategy after pyelonephritis must be identified.

PMID- 28437564
TI  - Conflicts of interest issues. Response to Lucas et al.

PMID- 28437565
TI  - Relaxed ordered subset preconditioned alternating projection algorithm for PET
      reconstruction with automated penalty weight selection.
AB  - PURPOSE: Performance of the preconditioned alternating projection algorithm
      (PAPA) using relaxed ordered subsets (ROS) with a non-smooth penalty function was
      investigated in positron emission tomography (PET). A higher order total
      variation (HOTV) regularizer was applied and a method for unsupervised selection
      of penalty weights based on the measured data is introduced. METHODS: A ROS
      version of PAPA with HOTV penalty (ROS-HOTV-PAPA) for PET image reconstruction
      was developed and implemented. Two-dimensional PET data were simulated using two
      synthetic phantoms (geometric and brain) in geometry similar to GE D690/710
      PET/CT with uniform attenuation, and realistic scatter (25%) and randoms (25%).
      Three count levels (high/medium/low) corresponding to mean information densities
      (ID-s) of 125, 25, and 5 noise equivalent counts (NEC) per support voxel were
      reconstructed using ROS-HOTV-PAPA. The patients' brain and whole body PET data
      were acquired at similar ID-s on GE D690 PET/CT with time-of-fight and were
      reconstructed using ROS-HOTV-PAPA and available clinical ordered-subset
      expectation-maximization (OSEM) algorithms. A power-law model of the penalty
      weights' dependence on ID- was semi-empirically derived. Its parameters were
      elucidated from the data and used for unsupervised selection of the penalty
      weights within a reduced search space. The resulting image quality was evaluated
      qualitatively, including reduction of staircase artifacts, image noise, spatial
      resolution and contrast, and quantitatively using root mean squared error (RMSE)
      as a global metric. The convergence rates were also investigated. RESULTS: ROS
      HOTV-PAPA converged rapidly, in comparison to non-ROS-HOTV-PAPA, with no evidence
      of limit cycle behavior. The reconstructed image quality was superior to
      optimally post-filtered OSEM reconstruction in terms of noise, spatial
      resolution, and contrast. Staircase artifacts were not observed. Images of the
      measured phantom reconstructed using ROS-HOTV-PAPA showed reductions in RMSE of
      5%-44% as compared with optimized OSEM. The greatest improvement occurred in the
      lowest count images. Further, ROS-HOTV-PAPA reconstructions produced images with
      RMSE similar to images reconstructed using optimally post-filtered OSEM but at
      one-quarter the NEC. CONCLUSION: Acceleration of HOTV-PAPA was achieved using
      ROS. This was accompanied by an improved RMSE metric and perceptual image quality
      that were both superior to that obtained with either clinical or optimized OSEM.
      This may allow up to a four-fold reduction of the radiation dose to the patients
      in a PET study, as compared with current clinical practice. The proposed
      unsupervised parameter selection method provided useful estimates of the penalty
      weights for the selected phantoms' and patients' PET studies. In sum, the
      outcomes of this research indicate that ROS-HOTV-PAPA is an appropriate candidate
      for clinical applications and warrants further research.

PMID- 28437566
TI  - Physical Therapists' Perceptions of Telephone- and Internet Video-Mediated
      Service Models for Exercise Management of People With Osteoarthritis.
AB  - OBJECTIVE: To investigate physical therapists' perceptions of, and willingness to
      use, telephone- and internet-mediated service models for exercise therapy for
      people with knee and/or hip osteoarthritis. METHODS: This study used an internet
      based survey of Australian physical therapists, comprising 3 sections: 1 on
      demographic information and 2 with 16 positively framed perception statements
      about delivering exercise via telephone and video over the internet, for people
      with hip and/or knee osteoarthritis. Levels of agreement with each statement were
      evaluated. Logistic regression models were used to determine therapist
      characteristics influencing interest in delivering telerehabilitation. RESULTS: A
      total of 217 therapists spanning metropolitan, regional, rural, and remote
      Australia completed the survey. For telephone-delivered care, there was consensus
      agreement that it would not violate patient privacy (81% agreed/strongly agreed)
      and would save patient's time (76%), but there was less than majority agreement
      for 10 statements. There was consensus agreement that video-delivered care would
      save a patient's time (82%), be convenient for patients (80%), and not violate
      patient privacy (75%). Most agreed with all other perception statements about
      video-delivered care, except for liking no physical contact (14%). Low confidence
      using internet video technologies, and inexperience with telerehabilitation, were
      significantly associated with reduced interest in delivering telephone and/or
      video-based services. CONCLUSION: Physical therapists agree that
      telerehabilitation offers time-saving and privacy advantages for people with
      osteoarthritis and perceive video-delivered care more favorably than telephone
      delivered services. However, most do not like the lack of physical contact with
      either service model. These findings may inform the implementation of
      telerehabilitation osteoarthritis services and the training needs of clinicians
      involved in delivering care.

PMID- 28437567
TI  - Pelvic and Hip Kinematics During Walking in People With Patellofemoral Joint
      Osteoarthritis Compared to Healthy Age-Matched Controls.
AB  - OBJECTIVE: Patellofemoral (PF) joint osteoarthritis (OA) is common, yet little is
      known about how this condition influences lower-extremity biomechanical function.
      This study compared pelvis and lower-extremity kinematics in people with and
      without PF joint OA. METHODS: Sixty-nine participants (64% women, mean +/- SD age
      56 +/- 10 years) with anterior knee pain aggravated by PF joint-loaded activities
      (e.g., stair ambulation, rising from sitting, or squatting) and radiographic
      lateral PF joint OA on skyline radiographs were compared with 18 controls (78%
      women, mean +/- SD age 53 +/- 7 years) with no lower-extremity pain or
      radiographic OA. Knee Injury and Osteoarthritis Outcome Score (KOOS) data were
      collected from participants with PF joint OA. Quantitative gait analyses were
      conducted during overground walking at a self-selected speed. Pelvis and lower
      extremity kinematics were calculated across the stance phase. Data were
      statistically analyzed using analyses of covariance, with age and sex as
      covariates (P < 0.05). RESULTS: Participants with PF joint OA reported a mean +/-
      SD KOOS pain subscale score of 65 +/- 15, KOOS symptoms subscale score of 63 +/-
      16, KOOS activities of daily living subscale score of 73 +/- 13, KOOS
      sports/recreation subscale score of 45 +/- 23, and KOOS quality of life subscale
      score of 43 +/- 16. Participants with PF joint OA walked with greater anterior
      pelvic tilt throughout the stance phase, as well as greater lateral pelvic tilt
      (i.e., pelvis lower on the contralateral side), greater hip adduction, and lower
      hip extension during the late stance phase. No differences in knee and ankle
      joint angles were observed between groups. CONCLUSION: People with PF joint OA
      walk with altered pelvic and hip movement patterns compared with aged-matched
      controls. Restoring normal movement patterns during walking in people with PF
      joint OA may be warranted to help alleviate symptoms.

PMID- 28437568
TI  - Insights into deep-sea adaptations and host-symbiont interactions: A comparative
      transcriptome study on Bathymodiolus mussels and their coastal relatives.
AB  - Mussels (Bivalve: Mytilidae) have adapted to various habitats, from fresh water
      to the deep sea. To understand their adaptive characteristics in different
      habitats, particularly in the bathymodiolin mussels in deep-sea chemosynthetic
      ecosystems, we conducted a comparative transcriptomic analysis between deep-sea
      bathymodiolin mussels and their shallow-water relatives. A number of gene
      families related to stress responses were shared across all mussels, without
      specific or significantly expanded families in deep-sea species, indicating that
      all mussels are capable of adapting to diverse harsh environments, but that
      different members of the same gene family may be preferentially utilized by
      different species. One of the most extraordinary trait of bathymodiolin mussels
      is their endosymbiosis. Lineage-specific and positively selected TLRs and highly
      expressed C1QDC proteins were identified in the gills of the bathymodiolins,
      suggesting their possible functions in symbiont recognition. However, pattern
      recognition receptors of the bathymodiolins were globally reduced, facilitating
      the invasion and maintenance of the symbionts obtained by either endocytosis or
      phagocytosis. Additionally, various transporters were positively selected or more
      highly expressed in the deep-sea mussels, indicating a means by which necessary
      materials could be provided for the symbionts. Key genes supporting lysosomal
      activity were also positively selected or more highly expressed in the deep-sea
      mussels, suggesting that nutrition fixed by the symbionts can be absorbed in a
      "farming" way wherein the symbionts are digested by lysosomes. Regulation of key
      physiological processes including lysosome activity, apoptosis and immune
      reactions is needed to maintain a stable host-symbiont relationship, but the
      mechanisms are still unclear.

PMID- 28437569
TI  - The shaken baby syndrome report was not the result of a conspiracy. Response to
      Dr. Narang et al.

PMID- 28437570
TI  - Self-Acupressure for Older Adults With Symptomatic Knee Osteoarthritis: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: This double-blind randomized controlled trial aimed to test the
      efficacy of self-administered acupressure for pain and physical function
      improvement for older adults with knee osteoarthritis (OA). METHODS: Participants
      were community-dwelling adults with symptomatic knee OA (n = 150, mean age 73
      years), randomized to 1 of 3 groups: verum acupressure, sham acupressure, or
      usual care. Participants in the verum and sham groups, but not those in the usual
      care group, were taught to self-apply acupressure once daily, 5 days/week for 8
      weeks. Assessments were collected during center visits at baseline, and at 4 and
      8 weeks. In addition, pain level was assessed weekly by phone using a numeric
      rating scale (NRS). Outcomes included the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) pain subscale (primary), and subjective
      and objective physical function measures and the NRS and physical function
      measures (secondary). Linear mixed regression analysis was conducted to test
      between-group differences in mean changes from baseline for the outcomes at 8
      weeks. RESULTS: Compared with usual care, both verum and sham acupressure
      participants experienced significant improvements in WOMAC pain (mean difference 
      1.27 units [95% confidence interval (95% CI) -1.95, -0.58] and -1.24 units [95%
      CI -1.92, -0.55], respectively), NRS pain (-0.74 units [95% CI -1.24, -0.24] and 
      0.51 units [95% CI -1.01, -0.01], respectively), and WOMAC function (-4.83 units
      [95% CI -6.99, -2.67] and -4.21 units [95% CI -6.37, -2.04], respectively) at 8
      weeks. There were no significant differences between the verum and sham
      acupressure groups on any of the outcomes. CONCLUSION: Self-administered
      acupressure is superior to usual care in pain and physical function improvement
      for older adults with knee OA. The reason for the benefits is unclear, and the
      placebo effect may play a role.

PMID- 28437571
TI  - Label-free high temporal resolution assessment of cell proliferation using
      digital holographic microscopy.
AB  - Cell proliferation assays are widely applied in biological sciences to understand
      the effect of drugs over time. However, current methods often assess cell
      population growth indirectly, that is, the cells are not actually counted.
      Instead other parameters, for example, the amount of protein, are determined.
      These methods often also demand phototoxic labels, have low temporal resolution,
      or employ end-point assays, and frequently are labor intensive. We have developed
      a robust and label-free kinetic cell proliferation assay with high temporal
      resolution for adherent cells using digital holographic microscopy (DHM), one of
      many quantitative phase microscopy techniques. As no labels or stains are
      required, and only very low intensity illumination is necessary, the technique
      allows for noninvasive continuous cell counting. Only two image processing
      settings were adjusted between cell lines, making the assay practical, user
      friendly, and free of user bias. The developed direct assay was validated by
      analyzing cell cultures treated with various concentrations of the anti-cancer
      drug etoposide, a well-established topoisomerase inhibitor that causes DNA damage
      and leads to programmed cell death. After treatment, the unstained adherent cells
      were nondestructively imaged every 30 min for 36 h inside a cell incubator. In
      the recorded time-lapse image sequences, individual cells were automatically
      identified to provide detailed growth curves and growth rate data of cell number,
      confluence, and average cell volume. Our results demonstrate how these parameters
      facilitate a deeper understanding of cell processes than what is achievable with
      current single-parameter and end-point methods. (c) 2017 International Society
      for Advancement of Cytometry.

PMID- 28437573
TI  - Using internal and external reviewers can help to optimise neonatal mortality and
      morbidity conferences.
AB  - AIM: This study determined whether there was a difference in the conclusions
      reached by neonatologists in morbidity and mortality conferences based on their
      level of involvement in a case. METHODS: All neonatal deaths occurring between
      August 2014 and September 2015 at the neonatal intensive care unit of Sainte
      Justine Hospital, Montreal, Quebec, Canada, were reviewed by internal physicians
      involved in the case and external physicians who were not. The reviewers were
      asked to identify positive and negative clinical practice items and provide
      written recommendations. These were classified into eight categories and compared
      for each case. RESULTS: During the study, 55 patients died leading to 110 reviews
      and a total of 590 positive and negative items. Most items were in the
      communication (25.2%), ethical decision-making (16.7%) and clinical management
      (14.8%) categories. Both the internal and external reviewers were in agreement
      48.5% of the time for positive items and 44.8% for negative items. There were 242
      written recommendations, which differed significantly among the internal and
      external reviewers. CONCLUSION: Reviews of neonatal deaths by two independent
      reviewers, internal physicians and external physicians, led to different positive
      and negative practice items and recommendations. This could allow for a richer
      discussion and improve recommendations for patient care.

PMID- 28437572
TI  - Nearly a decade-long repeatable seasonal diversity patterns of bacterioplankton
      communities in the eutrophic Lake Donghu (Wuhan, China).
AB  - Uncovering which environmental factors govern community diversity patterns and
      how ecological processes drive community turnover are key questions related to
      understand the community assembly. However, the ecological mechanisms regulating
      long-term variations of bacterioplankton communities in lake ecosystems remain
      poorly understood. Here we present nearly a decade-long study of bacterioplankton
      communities from the eutrophic Lake Donghu (Wuhan, China) using 16S rRNA gene
      amplicon sequencing with MiSeq platform. We found strong repeatable seasonal
      diversity patterns in terms of both common (detected in more than 50% samples)
      and dominant (relative abundance >1%) bacterial taxa turnover. Moreover,
      community composition tracked the seasonal temperature gradient, indicating that
      temperature is a key environmental factor controlling observed diversity
      patterns. Total phosphorus also contributed significantly to the seasonal shifts
      in bacterioplankton composition. However, any spatial pattern of bacterioplankton
      communities across the main lake areas within season was overwhelmed by their
      temporal variabilities. Phylogenetic analysis further indicated that 75%-82% of
      community turnover was governed by homogeneous selection due to consistent
      environmental conditions within seasons, suggesting that the microbial
      communities in Lake Donghu are mainly controlled by niche-based processes.
      Therefore, dominant niches available within seasons might be occupied by similar
      combinations of bacterial taxa with modest dispersal rates throughout different
      lake areas.

PMID- 28437574
TI  - Dietary lactalbumin and lactoferrin interact with inulin to modulate energy
      balance in obese rats.
AB  - OBJECTIVE: To determine whether diets enriched with the whey protein components
      lactalbumin and lactoferrin interact additively with inulin to improve energy
      balance by decreasing food intake and body weight (BW). METHODS: In four
      experiments, diet-induced obese rats were randomized to diets containing either
      lactalbumin or lactoferrin at low (20% kcal) or high (40% kcal) doses, and inulin
      at low (7.5% w/w) or high (15% w/w) doses, alone or in combination. Energy intake
      (EI), energy expenditure (EE), respiratory quotient (RQ), BW, body composition,
      plasma insulin, and leptin concentrations were measured. RESULTS: Lactalbumin and
      inulin at low doses were ineffective, whereas high doses additively decreased EI
      and RQ. Low doses of lactoferrin and inulin additively decreased EI, BW, fat and
      lean mass, and RQ. High doses of lactoferrin and inulin additively decreased EI,
      supra-additively decreased BW, fat, and lean mass, and also decreased RQ and
      plasma leptin concentrations. CONCLUSIONS: High doses of lactalbumin and inulin
      additively decreased EI. Importantly, lactoferrin and inulin at both low and high
      dose combinations, additively or supra-additively, decreased EI, BW, and
      adiposity.

PMID- 28437575
TI  - 24-segment sphericity index: a new technique to evaluate fetal cardiac diastolic
      shape.
AB  - OBJECTIVE: Because of parallel circulation in the fetus and the differential
      effect that various disease states may have on the shape of the right and left
      ventricles, this study was conducted to evaluate the sphericity index (SI) of 24
      transverse segments distributed from the base to the apex of each of the
      ventricular chambers. METHODS: Two hundred control fetuses were examined between
      20 and 40 weeks of gestation. The displacement of the ventricular endocardium
      during the cardiac cycle was computed using offline speckle-tracking software.
      From the ASCII output of the analysis, we analyzed 24 end-diastolic transverse
      segments, distributed from the base to the apex of each ventricle, as well as the
      end-diastolic mid-basal-apical length. The SI was computed for each of the 24
      segments by dividing the mid-basal-apical length by the transverse length for
      each segment. Regression analysis was performed against biometric measurements
      and gestational age according to last menstrual period and ultrasound. Eight
      fetuses, in which the four-chamber view appeared subjectively to demonstrate
      chamber disproportion, were evaluated as examples to demonstrate the utility of
      this technology. RESULTS: The SI for each segment was independent of gestational
      age and fetal biometric measurements. The SI of the right ventricle was
      significantly (P < 0.001) lower than that of the left ventricle for segments 1
      18, suggesting that the right ventricle was more globular in shape than was the
      left ventricle at the base, mid and a portion of the apical segments of the
      chamber. Fetuses with various cardiac structural abnormalities and abnormal fetal
      growth had abnormal SI values that reflected either a more globular or a more
      flattened ventricular chamber. CONCLUSION: Determination of SI for each of 24
      segments of the fetal right and left ventricles provides a comprehensive method
      to examine the shape of the ventricular chambers. Copyright (c) 2017 ISUOG.
      Published by John Wiley & Sons Ltd.

PMID- 28437576
TI  - Irisin and musculoskeletal health.
AB  - Irisin is a hormone-like myokine produced in abundance by skeletal muscle in
      response to exercise, both in mice and humans. Once released into the
      circulation, irisin acts on white adipocytes to induce the browning response and
      subsequently activates nonshivering thermogenesis. We have examined the premise
      that irisin produced during exercise may subserve further functions in the
      musculoskeletal system. We review evidence for its possible skeletal effects,
      including the central role that irisin plays in the control of bone mass, with
      positive effects on cortical mineral density and geometry in mice. We also review
      the autocrine effects of irisin in skeletal muscle, in which it upregulates the
      expression of its precursor (FNDC5). Since loss of bone and muscle mass occurs
      with aging, immobility, and several metabolic diseases, future studies exploring
      the efficacy of irisin in restoring bone and reversing muscle wasting could be
      important to establishing irisin as a molecule that combines beneficial effects
      for treating osteoporosis and muscular atrophy. If the results from mice were
      confirmed in human studies, an irisin-based therapy could be developed for
      physically disabled or bedridden patients.

PMID- 28437577
TI  - High gene flow despite opposite chirality in hybrid zones between enantiomorphic
      door snails.
AB  - We studied differentiation and geneflow patterns between enantiomorphic door
      snail species in two hybrid zones in the Bucegi Mountains (Romania) to
      investigate the effects of intrinsic barriers (complications in copulation) and
      extrinsic selection by environmental factors. A mitochondrial gene tree confirmed
      the historical separation of the examined populations into the dextral Alopia
      livida and the sinistral Alopia straminicollis in accordance with the
      morphological classification, but also indicated gene flow between the species.
      By contrast, a network based on amplified fragment length polymorphisms (AFLP)
      markers revealed local groups of populations as units independent of their
      species affiliation. Admixture analyses based on AFLP data showed that the
      genomes of most individuals in the hybrid zones are composed of parts of the
      genomes of both parental taxa. The introgression patterns of a notable fraction
      of the examined markers deviated from neutral introgression. However, the
      patterns of most non-neutral markers were not concordant between the two hybrid
      zones. There was also no concordance between non-neutral markers in the two
      genomic clines and markers that were correlated with environmental variables or
      markers that were correlated with the proportion of dextral individuals in the
      populations. Neither extrinsic selection by environmental factors nor intrinsic
      barriers resulting from positive frequency-dependent selection of the prevailing
      coiling direction were sufficient to maintain the distinctness of A.
      straminicollis and A. livida. Despite being historically separated units, we
      conclude that these taxa now merge where they come into contact.

PMID- 28437578
TI  - KLRG1 impairs regulatory T-cell competitive fitness in the gut.
AB  - Immune homeostasis requires the tight, tissue-specific control of the different
      CD4+ Foxp3+ regulatory T (Treg) cell populations. The cadherin-binding inhibitory
      receptor killer cell lectin-like receptor G1 (KLRG1) is expressed by a
      subpopulation of Treg cells with GATA3+ effector phenotype. Although such Treg
      cells are important for the immune balance, especially in the gut, the role of
      KLRG1 in Treg cells has not been assessed. Using KLRG1 knockout mice, we found
      that KLRG1 deficiency does not affect Treg cell frequencies in spleen, mesenteric
      lymph nodes or intestine, or frequencies of GATA3+ Treg cells in the gut. KLRG1
      deficient Treg cells were also protective in a T-cell transfer model of colitis.
      Hence, KLRG1 is not essential for the development or activity of the general Treg
      cell population. We then checked the effects of KLRG1 on Treg cell activation. In
      line with KLRG1's reported inhibitory activity, in vitro KLRG1 cross-linking
      dampened the Treg cell T-cell receptor response. Consistently, lack of KLRG1 on
      Treg cells conferred on them a competitive advantage in the gut, but not in
      lymphoid organs. Hence, although absence of KLRG1 is not enough to increase
      intestinal Treg cells in KLRG1 knockout mice, KLRG1 ligation reduces T-cell
      receptor signals and the competitive fitness of individual Treg cells in the
      intestine.

PMID- 28437579
TI  - Mosaic trisomy 1q: a recurring chromosome anomaly that is a diagnostic challenge
      and is associated with a Fryns-like phenotype.
AB  - OBJECTIVE: Trisomy of the long arm of chromosome 1 is a very rare cytogenetic
      anomaly that is difficult to diagnose because of tissue-limited mosaicism. This
      study aimed to further characterize the prenatal and post-natal findings
      associated with this anomaly, including the first reported chromosomal microarray
      finding. METHOD: This is a retrospective study of six cases of mos
      46,X,der(Y)t(Y;1)(q12;q21)/46,XY, diagnosed both prenatally and post-natally.
      Detailed clinical features and pregnancy outcome were documented. RESULTS:
      Recurrent prenatal and post-natal features of our case series, as well as the
      previously reported cases, were described, suggesting a Fryns-like phenotype. A
      diagnosis of mosaic trisomy 1q is difficult to confirm post-natally in some cases
      because of the tissue provided for analysis, emphasizing the need to study
      multiple tissue types in cases of fetal loss with a suspected underlying
      chromosomal imbalance. CONCLUSION: The overlap of clinical features between
      mosaic trisomy 1q and Fryns syndrome emphasizes the need to obtain appropriate
      samples for genetic analysis. The present cases and a review of the literature
      suggest that partial trisomy of the long arm of chromosome 1 is a distinct de
      novo clinical entity with low recurrence risk. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28437580
TI  - Differential gene expression in narrow- and broad-headed European glass eels
      (Anguilla anguilla) points to a transcriptomic link of head shape dimorphism with
      growth rate and chemotaxis.
AB  - One of the major challenges in evolutionary biology is to understand the
      mechanisms underlying morphological dimorphism and plasticity, including the
      genomic basis of traits and links to ecology. At the yellow eel stage of the
      European eel (Anguilla anguilla), two morphotypes are found: broad- and narrow
      heads. This dimorphism has been linked to dietary differences, with broad-heads
      feeding on harder, larger prey than narrow-heads. However, recent research showed
      that both morphotypes could be distinguished at the glass eel stage, the
      nonfeeding predecessor of the yellow eel stage, implying that nondietary factors
      play a role in the development of this head shape dimorphism. Here, we used
      transcriptome profiling (RNAseq) to identify differentially expressed genes
      between broad- and narrow-headed glass eels. We found 260 significantly
      differentially expressed genes between the morphotypes, of which most were
      related to defence and immune responses. Interestingly, two genes involved in
      growth (soma and igf2) were significantly upregulated in narrow-heads, while nine
      genes involved in chemotaxis showed significant differential expression. Thus, we
      found support for the observation that head shape is associated with somatic
      growth, with fast-growing eels developing a narrower head. Additionally,
      observations in the wild have shown that slow-growers prefer freshwater, while
      fast-growers prefer brackish water. The differential expression of genes involved
      in chemotaxis seems to indicate that glass eel growth rate and habitat choice are
      linked. We hypothesize that two levels of segregation could take place in the
      European eel: first according to habitat choice and second according to feeding
      preference.

PMID- 28437581
TI  - Enhancement of Oxidative Desulfurization Performance over UiO-66(Zr) by Titanium
      Ion Exchange.
AB  - Oxidative desulfurization is considered to be one of the most promising methods
      for producing ultra-low-sulfur fuels because it can effectively remove refractory
      sulfur-containing aromatic compounds under mild conditions. In this work, the
      oxidative desulfurization performance over UiO-66(Zr) is greatly enhanced by Ti
      ion exchange. This strategy is not only efficient for UiO-66(Zr) with crystal
      defects but also for UiO-66(Zr) with high crystallinity. In particular, the
      performance of UiO-66(Zr) with high crystallinity in the oxidative
      desulfurization of dibenzothiophene can be improved more than 11-fold, which can
      be mainly attributed to the introduction of active Ti sites.

PMID- 28437582
TI  - Modified frailty index predicts postoperative outcomes in older gastrointestinal
      cancer patients.
AB  - BACKGROUND AND OBJECTIVES: Frailty disproportionately impacts older patients with
      gastrointestinal cancer, rendering them at increased risk for poor outcomes. A
      frailty index may aid in preoperative risk stratification. We hypothesized that
      high modified frailty index (mFI) scores are associated with adverse outcomes
      after tumor resection in older, gastrointestinal cancer patients. METHODS:
      Patients (60-90 years old) who underwent gastrointestinal tumor resection were
      identified in the 2005-2012 NSQIP Participant Use File. mFI was defined by 11
      previously described, preoperative variables. Frailty was defined by an mFI score
      >0.27. The postoperative course was evaluated using univariate and multivariate
      analysis. RESULTS: 41 455 patients (mean age 72.4 years, 47.4% female) were
      identified. The most prevalent form of cancer was colorectal (69.3%, n = 28 708)
      and 2.8% of patients were frail (n = 1,164). Frail patients were significantly
      more likely to have increased length of stay (11.7 vs 9.0 days), major
      complications (29.1% vs 17.9%), and 30-day mortality (5.6% vs 2.5%), (all P <
      0.001). Multivariate analysis identified mFI as an independent predictor of major
      complications (OR 1.52, 95%CI 1.39-1.65, P < 0.001) and 30-day mortality (OR
      1.48, 95%CI 1.24-1.75, P < 0.001). CONCLUSIONS: mFI was associated with the
      incidence of postoperative complications and mortality in older surgical patients
      with gastrointestinal cancer.

PMID- 28437583
TI  - Natural selection on MHC IIbeta in parapatric lake and stream stickleback:
      Balancing, divergent, both or neither?
AB  - Major histocompatibility complex (MHC) genes encode proteins that play a central
      role in vertebrates' adaptive immunity to parasites. MHC loci are among the most
      polymorphic in vertebrates' genomes, inspiring many studies to identify
      evolutionary processes driving MHC polymorphism within populations and divergence
      between populations. Leading hypotheses include balancing selection favouring
      rare alleles within populations, and spatially divergent selection. These
      hypotheses do not always produce diagnosably distinct predictions, causing many
      studies of MHC to yield inconsistent or ambiguous results. We suggest a novel
      strategy to distinguish balancing vs. divergent selection on MHC, taking
      advantage of natural admixture between parapatric populations. With divergent
      selection, individuals with immigrant alleles will be more infected and less fit
      because they are susceptible to novel parasites in their new habitat. With
      balancing selection, individuals with locally rare immigrant alleles will be more
      fit (less infected). We tested these contrasting predictions using three-spine
      stickleback from three replicate pairs of parapatric lake and stream habitats. We
      found numerous positive and negative associations between particular MHC IIbeta
      alleles and particular parasite taxa. A few allele-parasite comparisons supported
      balancing selection, and others supported divergent selection between habitats.
      But, there was no overall tendency for fish with immigrant MHC alleles to be more
      or less heavily infected. Instead, locally rare MHC alleles (not necessarily
      immigrants) were associated with heavier infections. Our results illustrate the
      complex relationship between MHC IIbeta allelic variation and spatially varying
      multispecies parasite communities: different hypotheses may be concurrently true
      for different allele-parasite combinations.

PMID- 28437584
TI  - High-field 95 Mo and 183 W static and MAS NMR study of polyoxometalates.
AB  - The potential of high-field NMR to measure solid-state 95 Mo and 183 W NMR in
      polyoxometalates (POMs) is explored using some archetypical structures like
      Lindqvist, Keggin and Dawson as model compounds that are well characterized in
      solution. NMR spectra in static and under magic angle spinning (MAS) were
      obtained, and their analysis allowed extraction of the NMR parameters, including
      chemical shift anisotropy and quadrupolar coupling parameters. Despite the
      inherent difficulties of measurement in solid state of these low-gamma NMR
      nuclei, due mainly to the low spectral resolution and poor signal-to-noise ratio,
      the observed global trends compare well with the solution-state NMR data. This
      would open an avenue for application of solid-state NMR to POMs, especially when
      liquid-state NMR is not possible, e.g., for poorly soluble or unstable compounds
      in solution, and for giant molecules with slow tumbling motion. This is the case
      of Keplerate where we provide here the first NMR characterization of this class
      of POMs in the solid state. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28437585
TI  - Chronic intestinal electrical stimulation improves glucose intolerance and
      insulin resistance in diet-induced obesity rats.
AB  - OBJECTIVE: Obesity is a contributing factor to insulin resistance and type 2
      diabetes. The aim of this study was to study the therapeutic potential of
      intestinal electrical stimulation (IES) for obesity and associated glucose
      intolerance and insulin resistance in diet-induced obesity (DIO) rats. METHODS:
      DIO rats were divided into two groups to receive sham or IES for 8 weeks. Oral
      glucose tolerance and insulin tolerance tests were performed. Gastric emptying
      and small bowel transit tests were performed. Blood samples were collected for
      the analysis of insulin and free fatty acid (FFA). RESULTS: Chronic IES reduced
      food intake and body weight and decreased the adiposity index in DIO rats.
      Compared with chow-fed rats, DIO rats had an elevated fasting plasma glucose
      level, impaired glucose tolerance, and impaired insulin sensitivity, which were
      improved after chronic IES. FFA was elevated in DIO rats and suppressed with IES.
      Chronic IES delayed gastric emptying but accelerated small bowel transit.
      CONCLUSIONS: IES reduces food intake and body weight and improves glucose
      tolerance and insulin resistance in DIO rats. The ameliorating effect on glycemic
      control may be due to the weight loss and suppression of plasma FFA. Other
      mechanisms such as the modulation of gastrointestinal transit may also be
      involved.

PMID- 28437587
TI  - Relationship type affects the reliability of dispersal distance estimated using
      pedigree inferences in partially sampled populations: A case study involving
      invasive American mink in Scotland.
AB  - Estimating dispersal-a key parameter for population ecology and management-is
      notoriously difficult. The use of pedigree assignments, aided by likelihood-based
      software, has become popular to estimate dispersal rate and distance. However,
      the partial sampling of populations may produce false assignments. Further, it is
      unknown how the accuracy of assignment is affected by the genealogical
      relationships of individuals and is reflected by software-derived assignment
      probabilities. Inspired by a project managing invasive American mink (Neovison
      vison), we estimated individual dispersal distances using inferred pairwise
      relationships of culled individuals. Additionally, we simulated scenarios to
      investigate the accuracy of pairwise inferences. Estimates of dispersal distance
      varied greatly when derived from different inferred pairwise relationships, with
      mother-offspring relationship being the shortest (average = 21 km) and the most
      accurate. Pairs assigned as maternal half-siblings were inaccurate, with 64%-97%
      falsely assigned, implying that estimates for these relationships in the wild
      population were unreliable. The false assignment rate was unrelated to the
      software-derived assignment probabilities at high dispersal rates. Assignments
      were more accurate when the inferred parents were older and immigrants and when
      dispersal rates between subpopulations were low (1% and 2%). Using 30 instead of
      15 loci increased pairwise reliability, but half-sibling assignments were still
      inaccurate (>59% falsely assigned). The most reliable approach when using
      inferred pairwise relationships in polygamous species would be not to use half
      sibling relationship types. Our simulation approach provides guidance for the
      application of pedigree inferences under partial sampling and is applicable to
      other systems where pedigree assignments are used for ecological inference.

PMID- 28437586
TI  - Pathogenesis of vascular leak in dengue virus infection.
AB  - Endothelial dysfunction leading to vascular leak is the hallmark of severe
      dengue. Vascular leak typically becomes clinically evident 3-6 days after the
      onset of illness, which is known as the critical phase. This critical phase
      follows the period of peak viraemia, and lasts for 24-48 hr and usually shows
      rapid and complete reversal, suggesting that it is likely to occur as a result of
      inflammatory mediators, rather than infection of the endothelium. Cytokines such
      as tumour necrosis factor-alpha, which are known to be elevated in the critical
      phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble
      viral protein, has also been shown to disrupt the endothelial glycocalyx and thus
      contribute to vascular leak, although there appears to be a discordance between
      the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many
      inflammatory lipid mediators are elevated in acute dengue viral infection such as
      platelet activating factor (PAF) and leukotrienes. Furthermore, many other
      inflammatory mediators such as vascular endothelial growth factor and
      angiopoietin-2 have been shown to be elevated in patients with dengue
      haemorrhagic fever, exerting their action in part by inducing the activity of
      phospholipases, which have diverse inflammatory effects including generation of
      PAF. Platelets have also been shown to significantly contribute to endothelial
      dysfunction by production of interleukin-1beta through activation of the NLRP3
      inflammasome and also by inducing production of inflammatory cytokines by
      monocytes. Drugs that block down-stream immunological mediator pathways such as
      PAF may also be beneficial in the treatment of severe disease.

PMID- 28437588
TI  - Enhanced Solar Water Splitting by Swift Charge Separation in Au/FeOOH Sandwiched
      Single-Crystalline Fe2 O3 Nanoflake Photoelectrodes.
AB  - In this work, single crystalline alpha-Fe2 O3 nanoflakes (NFs) are formed in a
      highly dense array by Au seeding of a Fe substrate by a thermal oxidation
      technique. The NFs are conformally decorated with a thin FeOOH cocatalyst layer.
      Photoelectrochemical (PEC) measurements show that this photoanode, incorporating
      alpha-Fe2 O3 /FeOOH NFs rooted on the Au/Fe structure, exhibits significantly
      enhanced PEC water oxidation performance compared to the plain alpha-Fe2 O3
      nanostructure on the Fe substrate. The alpha-Fe2 O3 /FeOOH NFs on Au/Fe
      photoanode yields a photocurrent density of 3.1 mA cm-2 at 1.5 VRHE , and a
      remarkably low onset potential of 0.5-0.6 VRHE in 1 m KOH under AM 1.5G (100 mW
      cm-2 ) simulated sunlight illumination. The enhancement in PEC performance can be
      attributed to a synergistic effect of the FeOOH top decoration and the Au
      underlayer, whereby FeOOH facilitates hole transfer at the interface of
      electrode/electrolyte and the Au layer provides a sink for the electron transport
      to the back contact. This results in a drastically improved charge-separation
      efficiency in the single crystalline alpha-Fe2 O3 NF photoanode.

PMID- 28437589
TI  - The roles of ecology, behaviour and effective population size in the evolution of
      a community.
AB  - Organismal traits such as ecological specialization and migratory behaviour may
      affect colonization potential, population persistence and degree of isolation,
      factors that determine the composition and genetic structure of communities.
      However, studies focusing on community assembly rarely consider these factors
      jointly. We sequenced 16 nuclear genes and one mitochondrial gene from Caucasian
      and European populations of 30 forest-dwelling avian species that represent
      diverse ecological (specialist-generalist) and behavioural (migratory-resident)
      backgrounds. We tested the effects of organismal traits on population divergence
      and community assembly in the Caucasus forest, a continental mountain island
      setting. We found that (i) there is no concordance in divergence times between
      the Caucasus forest bird populations and their European counterparts, (ii)
      habitat specialists tend to be more divergent than generalists and (iii)
      residents tend to be more divergent than migrants. Thus, specialists and
      residents contribute to the high level of endemism of Caucasus forest avifauna
      more than do generalists and migrants. Patterns of genetic differentiation are
      better explained by differences in effective population sizes, an often
      overlooked factor in comparative studies of phylogeography and speciation, than
      by divergence times or levels of gene flow. Our results suggest that the Caucasus
      forest avifauna was assembled through time via dispersal and/or multiple
      vicariant events, rather than originating simultaneously via a single isolation
      event. Our study is one of the first multilocus, multispecies analyses revealing
      how ecological and migratory traits impact the evolutionary history of community
      formation on a continental island.

PMID- 28437590
TI  - Plant dual-specificity tyrosine phosphorylation-regulated kinase optimizes light
      regulated growth and development in Arabidopsis.
AB  - Light controls vegetative and reproductive development of plants. For a plant,
      sensing the light input properly ensures coordination with the ever-changing
      environment. Previously, we found that LIGHT-REGULATED WD1 (LWD1) and LWD2
      regulate the circadian clock and photoperiodic flowering. Here, we identified
      Arabidopsis YET ANOTHER KINASE1 (AtYAK1), an evolutionarily conserved protein and
      a member of dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs),
      as an interacting protein of LWDs. Our study revealed that AtYAK1 is an important
      regulator for various light responses, including the circadian clock,
      photomorphogenesis and reproductive development. AtYAK1 could antagonize the
      function of LWDs in regulating the circadian clock and photoperiodic flowering.
      By examining phenotypes of atyak1, we found that AtYAK1 regulated light-induced
      period-length shortening and photomorphogenic development. Moreover, AtYAK1
      mediated plant fertility especially under inferior light conditions including low
      light and short-day length. This study discloses a new regulator connecting
      environmental light to plant growth.

PMID- 28437591
TI  - Fluorofenidone attenuates interleukin-1beta production by interacting with NLRP3
      inflammasome in unilateral ureteral obstruction.
AB  - AIM: We explored whether Fluorofenidone reduced interleukin-1beta (IL-1beta)
      production by interacting with NLRP3 inflammasome in unilateral ureteral
      obstruction (UUO). METHODS: Ureteral obstruction rats were treated with
      Fluorofenidone (500 mg/kg per day) for 3, 7 days. Morphologic analysis and
      leukocytes infiltration were assessed in ligated kidneys. Furthermore, plasmids
      of NLRP3, ASC, pro-Caspase-1, pro-IL-1beta were co-transfected into 293 T cells,
      and then treated with Fluorofenidone (2 mM). The expression of NLRP3, ASC, pro
      caspase-1, cleavage caspase-1, pro-IL-1beta and cleavage IL-1beta were measured
      by Western blot or real-time PCR in vivo and in vitro. Moreover the interaction
      of NLRP3 inflammasome-assembly was detected by co-immunoprecipitation and
      confocal immunofluorescence. RESULTS: Fluorofenidone treatment significantly
      attenuated renal fibrosis and leukocytes infiltration in UUO model.
      Fluorofenidone had no effect on the expression of pro-IL-1beta. Interestingly,
      Fluorofenidone inhibited the activation of NLRP3 inflammasome, downregulated
      Caspase-1 levels and thereby decreased the cleavage of pro-IL-1beta into IL-1beta
      in vivo and in vitro. Fluorofenidone treatment distinctively weakened the
      interaction between NLRP3 and ASC, as well as ASC and pro-Caspase-1 in vivo.
      However, Fluorofenidone treatment only significantly weakened the interaction
      between ASC and pro-Caspase-1 in co-transfected 293 T cells. CONCLUSION:
      Fluorofenidone serves as a novel anti-inflammatory agent that attenuates IL-1beta
      production in UUO model by interacting with NLRP3 inflammasome.

PMID- 28437593
TI  - Tabula rasa in the Patagonian Channels? The phylogeography of Oreobolus
      obtusangulus (Cyperaceae).
AB  - The extent of the Pleistocene glaciations in the Patagonian Channel region
      (southwesternmost South America) and their impact on the vegetation there are
      largely unknown. Whether the regional flora was wiped out completely (tabula
      rasa) or survived in ice-free pockets (in situ survival) is still an open
      question. The molecular imprint of either scenario should still be visible in
      extant populations. Therefore, DNA sequence data of Oreobolus obtusangulus
      Gaudich. (Cyperaceae) were analysed. This species is an abundant constituent of
      Patagonian cushion peat bogs, one of the Patagonian Channel region's major
      vegetation types. Three hundred and eighty-four individuals from 48 populations
      were sequenced for two chloroplast (ycf3-psaA and trnQUUG -psbK intergenic
      spacers) and 14 nuclear loci containing simple sequence repeats (SSRs;
      microsatellites). Phylogenetic reconstructions and the geographic distribution of
      genetic diversity revealed that the species was split into three main lineages
      whose general distributions comprise three separate major regions, that is, south
      central Chile, Fuego-Patagonia and the East Patagonian Andes, which probably
      constitute glacial refugia. Postglacial migration fronts formed a suture zone
      with high levels of genetic diversity in the Northwest Patagonian Andes, where
      remnants of a supposedly ancestral lineage were also found to be locally
      restricted to a single population (Huinay). The heavily glaciated Patagonian
      Channels were likely recolonized from the northwest, and partly from the south.
      Although the westernmost Patagonian Channel population (Estero Bachem) harboured
      private SSR alleles (singletons) and showed slightly elevated genetic diversity,
      it remained unclear whether this population actually survived in situ. This study
      helps fill a major gap in reconstructing the Pleistocene vegetation history of
      West and Andean Patagonia.

PMID- 28437594
TI  - A Mesoamerican origin of cherimoya (Annona cherimola Mill.): Implications for the
      conservation of plant genetic resources.
AB  - Knowledge on the structure and distribution of genetic diversity is a key aspect
      to plan and execute an efficient conservation and utilization of the genetic
      resources of any crop as well as for determining historical demographic
      inferences. In this work, a large data set of 1,765 accessions of cherimoya
      (Annona cherimola Mill, Annonaceae), an underutilized fruit tree crop native to
      the Neotropics and used as a food source by pre-Columbian cultures, was collected
      from six different countries across the American continent and amplified with
      nine highly informative microsatellite markers. The structure analyses, fine
      representation of the genetic diversity and an ABC approach suggest a
      Mesoamerican origin of the crop, contrary to previous reports, with clear
      implications for the dispersion of plant germplasm between Central and South
      America in pre-Columbian times. These results together with the potential
      distribution of the species in a climatic change context using two different
      climate models provide new insights for the history and conservation of extant
      genetic resources of cherimoya that can be applied to other currently
      underutilized woody perennial crops.

PMID- 28437596
TI  - Membrane transport status does not predict peritonitis risk in patients on
      peritoneal dialysis.
AB  - AIM: The aim of this study is to determine whether peritoneal membrane transport
      status (MTS) is associated with peritonitis or poor peritoneal dialysis-related
      outcomes. METHODS: This retrospective cohort study analysed data of incident
      adult patients on peritoneal dialysis in Western Sydney between 1 October 2003
      and 31 December 2012. Only patients who underwent peritoneal equilibration and
      adequacy tests within 6 months of commencement were included. Kaplan-Meier
      survival curves for time until first peritonitis and time until composite
      endpoint of peritonitis, death or technique failure, censored for transplant,
      were constructed. RESULTS: About 397 patients, mean age 58.8(+/-2SD29) years,
      body mass index (BMI) 26.6(+/-5) kg/m2 and serum albumin 35.4(+/-5) g/L were
      included. About 59.2% had high/high-average peritoneal MTS; 45.8% were past and
      current smokers; 51.9% developed at least one episode of peritonitis; 7.6%
      changed to haemodialysis; 6.3% underwent transplantation; 8.8% died; and 25.4%
      remained free of the aforementioned events over a mean follow-up period of 22.5
      months (range 0-115 months). Peritoneal MTS was not associated with time to first
      peritonitis (p = 0.67) or composite endpoint of peritonitis, death or technique
      failure (p = 0.12). Smoking and hypoalbuminaemia independently predicted time to
      first peritonitis. Past and current smokers had a hazard ratio of 1.38 (95% CI
      1.03-1.86) for shorter time to first peritonitis, significant after adjustment
      for serum albumin (p = 0.033). Serum albumin <32 g/L had a hazard ratio of 1.74
      (95% CI 1.13-2.67) for shorter time to first peritonitis, significant after
      adjusting for smoking (p = 0.012). CONCLUSION: Smoking and hypoalbuminaemia, but
      not MTS, were associated with shorter time to first peritonitis and composite
      endpoint of peritonitis, death and technique failure.

PMID- 28437597
TI  - Weight loss in Weight Watchers Online with and without an activity tracking
      device compared to control: A randomized trial.
AB  - OBJECTIVE: To evaluate a commercial online weight loss program and activity
      tracker, which are popular but have unknown efficacy. METHODS: Two hundred
      seventy-nine participants with BMI 27 to 40 kg/m2 were randomized to 12 months of
      the Weight Watchers Online program alone (WWO) or with the ActiveLink(r) activity
      tracking device (WWO+AL) or an online newsletter (Control). RESULTS: Weight
      losses at 3 months were significantly greater in WWO (2.7 kg [95% confidence
      interval (CI), 2.0-3.5 kg] than Control (1.3 kg [95% CI, 0.5-2.0 kg]; P = 0.01);
      neither differed from WWO+AL (2.0 kg [95% CI, 1.3-2.7 kg]; Ps > 0.56).
      Significantly more WWO participants (24.5%) achieved >= 5% weight loss at 3
      months than Control (9.4%) (P = 0.01); neither differed from WWO+AL (17.6%) (Ps =
      0.13-0.28). At 12 months, there were no significant differences between groups in
      weight loss (Ps > 0.52). WWO (25.5%) continued to have a higher proportion of
      participants achieving >= 5% weight loss than Control (12.9%) (P = 0.04); neither
      differed from WWO+AL (14.3%) (Ps > 0.10). There were no significant between-group
      differences in change in physical activity (Ps > 0.17). CONCLUSIONS: WWO produced
      significantly more weight loss at 3 months relative to Control, but not at 12
      months. Significantly more WWO than Control participants lost >= 5% at both 3 and
      12 months. Participants receiving an activity tracking device did not achieve
      greater weight loss or physical activity increases than those in a Control
      condition.

PMID- 28437598
TI  - The potential implications of using disability-free survival and number needed to
      suffer as outcome measures for neonatal intensive care.

PMID- 28437600
TI  - How Are Behavioral Theories Used in Interventions to Promote Physical Activity in
      Rheumatoid Arthritis? A Systematic Review.
AB  - OBJECTIVE: To identify the use of behavioral theories in physical activity
      interventions in populations with rheumatoid arthritis (RA). METHODS: This review
      includes articles published in English between January 1, 1980 and November 8,
      2015 in MEDLINE, Cochrane, and CINAHL, identified by a strategic literature
      search. Included studies were published in international peer-reviewed journals,
      mentioned theory, evaluated a physical activity intervention for adults with RA,
      and had >=1 physical activity variable as the outcome. References and reviews
      were also checked. Two investigators independently selected articles and
      extracted data using a validated scale, the theory coding scheme. Additional
      extracted data included author, sample characteristics, study design, physical
      activity outcomes, intervention type and duration, and control group. RESULTS: A
      total of 245 articles were identified, 211 articles and references were screened,
      and 29 articles were reviewed. Of these, 18 were excluded, leaving 11 articles
      with 1,472 participants (75% women). Ten studies (91%) were randomized controlled
      trials, 8 (73%) assessed physical activity plus self-management, and 3 (27%)
      physical activity only. Program durations ranged from 5 weeks to 1 year. Eight
      studies (73%) used a single theory, 7 studies (64%) linked at least 1
      intervention technique to theory, 2 studies (18%) analyzed mediating effects of
      theoretical constructs, and 5 studies (45%) discussed results in relation to
      theory. CONCLUSION: Findings indicate that physical activity intervention studies
      claiming the use of behavioral theories use theory to a small extent. We suggest
      expanding theory use in design, evaluation, and interpretation of physical
      activity intervention results. Further, we recommend that future studies evaluate
      the most salient behavioral theories, interventions components, and delivery
      modes in RA populations.

PMID- 28437595
TI  - Natural History and Predictors of Progression to Sjogren's Syndrome Among
      Participants of the Sjogren's International Collaborative Clinical Alliance
      Registry.
AB  - OBJECTIVE: To explore changes in the phenotypic features of Sjogren's syndrome
      (SS), and in SS status among participants in the Sjogren's International
      Collaborative Clinical Alliance (SICCA) registry over a 2-3-year interval.
      METHODS: All participants in the SICCA registry who were found to have any
      objective measures of salivary hypofunction, dry eye, focal lymphocytic
      sialadenitis in minor salivary gland biopsy, or anti-SSA/SSB antibodies were
      recalled over a window of 2 to 3 years after their baseline examinations to
      repeat all clinical examinations and specimen collections to determine whether
      there was any change in phenotypic features and in SS status. RESULTS: As of
      September 15, 2013, a total of 3,514 participants had enrolled in SICCA, and
      among 3,310 eligible, 771 presented for a followup visit. Among participants
      found to have SS using the 2012 American College of Rheumatology (ACR)
      classification criteria, 93% again met the criteria after 2 to 3 years, and this
      proportion was 89% when using the 2016 ACR/European League Against Rheumatism
      (EULAR) criteria. Among those who did not meet ACR or ACR/EULAR criteria at
      baseline, 9% and 8%, respectively, had progressed and met them at followup. Those
      with hypergammaglobulinemia and hypocomplementemia at study entry were,
      respectively, 4 and 6 times more likely to progress to SS by ACR criteria than
      those without these characteristics (95% confidence interval 1.5-10.1 and 1.8
      20.4, respectively). CONCLUSION: While there was stability over a 2-3-year period
      of both individual phenotypic features of SS and of SS status,
      hypergammaglobulinemia and hypocomplementemia at study entry were predictive of
      progression to SS.

PMID- 28437599
TI  - Human beta-defensin-3 induces IL-8 release and apoptosis in airway smooth muscle
      cells.
AB  - BACKGROUND: Human airway smooth muscle cells (ASMCs) may have a pro-inflammatory
      role through the release of inflammatory mediators. Increasing evidence indicates
      that human beta-defensins (HBDs) are related to pathogenesis of asthma.
      OBJECTIVES: To examine the plasma level of HBD-1, HBD-2 and HBD-3 in asthmatic
      patients and the expression of their mouse orthologues in the lung tissue of a
      mouse model of chronic severe asthma. Further to investigate the effect of HBD-3
      on the release of the pro-inflammatory cytokine IL-8 and to explore the
      mechanisms. METHODS: The plasma levels of HBD-1, HBD-2 and HBD-3 from 34 healthy
      controls and 25 asthmatic patients were determined by ELISA. The expression of
      mouse beta-defensins MBD-1, MBD-3 and MBD-14 in the lung tissue of asthmatic mice
      was detected by Western blot. The ASMCs were cultured with HBD-3 for 24 hour, and
      then the supernatant level of IL-8 was evaluated by ELISA and the cell viability
      was examined by WST-1 assay. The signalling pathway was investigated with
      blocking antibodies or pharmacological inhibitors. RESULTS: The plasma levels of
      HBD-1 and HBD-3 were elevated in asthmatic patients, and the expression of MBD
      14, the mouse orthologue for HBD-3, was increased in asthmatic mice. HBD-3
      induced IL-8 production in a CCR6 receptor-specific manner and was dependent on
      multiple signalling pathways. Moreover, HBD-3-induced cell apoptosis
      concurrently, which was dependent on the ERK1/2 MAPK pathway. Mitochondrial ROS
      regulated both HBD-3-induced IL-8 production and cell apoptosis. CONCLUSIONS AND
      CLINICAL RELEVANCE: These observations provide clear evidence of an important new
      mechanism for the promotion of airway inflammation and tissue remodelling with
      potential relevance for the treatment of asthma.

PMID- 28437601
TI  - Maternal hemodynamics in normal pregnancy: reference ranges and role of maternal
      characteristics.
AB  - OBJECTIVES: The main aim of this study was to construct reference ranges of
      maternal central hemodynamic parameters during pregnancy. The second aim was to
      determine the maternal and pregnancy characteristics that influence these
      hemodynamic parameters. METHODS: This was a prospective cohort study of low-risk
      pregnant women attending for routine antenatal care at St George's Hospital,
      London, UK. Exclusion criteria included any medical disorder present at the time
      of study recruitment, or development of hypertension or intrauterine fetal growth
      restriction following study recruitment. Stroke volume (SV), cardiac output (CO)
      and systemic vascular resistance (SVR) were obtained using non-invasive cardiac
      output monitoring (USCOM-1A(r)). USCOM-1A utilizes a non-imaging probe in the
      suprasternal notch to obtain velocity-time integrals of transaortic blood flow at
      the left ventricular outflow tract. Once the distribution of the data with
      respect to gestational age had been determined, maternal characteristics were
      added to the model to test whether they provided a significant improvement in the
      prediction of the median value. RESULTS: The study included 627 women with a
      singleton pregnancy. The estimated median CO was constant for a maternal age
      above 32 years, but was around 0.5 L/min higher for women aged <= 25 years (P <
      0.001). Maternal weight (P < 0.001) and height (P < 0.001) significantly affected
      CO values and there was a significant interaction (P = 0.002) between them. In
      women with a height of less than 1.60 m, there was no association between median
      CO and weight; however, in those with a height exceeding 1.60 m, an increase in
      weight was associated with an increase in CO. SV was primarily associated with
      height (P < 0.001), although some positive association with weight (P < 0.001)
      could also be observed within the normal body-mass-index range. Greater height (P
      < 0.001) was associated with lower median values of SVR, with an estimated
      difference of around 120 dynes * s/cm5 between 1.60 m and 1.80 m. Advancing
      maternal age was associated with higher median SVR, with an estimated difference
      of around 50 dynes * s/cm5 between 25 and 35 years. Smokers had a lower SVR by
      73.5 (95% CI, 8.6-138.4) dynes * s/cm5 . CONCLUSION: Maternal hemodynamics are
      influenced significantly by maternal age, height and weight. We provide USCOM-1A
      specific reference ranges and a calculator for SV, CO and SVR in uncomplicated
      pregnancies that correct for maternal age, height and weight. This should enable
      clinical application and comparison in both uncomplicated and pathological
      pregnancies. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28437602
TI  - Holography, machine learning, and cancer cells.

PMID- 28437603
TI  - What are acceptable conclusions? Response to Dr. Ludvigsson.

PMID- 28437605
TI  - Aqueously Released Graphene Oxide Embedded in Epoxy Resin Exhibits Different
      Characteristics and Phytotoxicity of Chlorella vulgaris from the Pristine Form.
AB  - The environmental release of nanoparticles is attracting increasing attention.
      Graphene oxide (GO) embedded in epoxy resin (ER) is a popular composite that has
      been used in various fields, but the environmental release of GO-ER composites
      and the effects on organisms in the environment remain unknown. The present work
      found that GO-ER composites in water for 2-7 days resulted in the release of 0.3
      2.1% GO-ER at nanoscale (2-3 nm thickness and approximately 70-130 nm lateral
      length). Interestingly, pristine GO quenched 30-45% hydroxyl and 12% nitroxide
      free radicals, whereas this capacity was not observed for the released particles
      from GO-ER. At environmentally relevant concentrations (MUg/L), released GO-ER
      particles, but not GO or ER matrix, promoted algal reproduction by 34% and
      chlorophyll biosynthesis by 65-127% at 96 h. Released GO-ER entered algal cells
      and induced a slight increase in reactive oxygen species but did not elicit
      notable cell structure damage. The upregulated amino acids and phenylalanine
      metabolism, and the downregulated fatty acid biosynthesis contributed to algal
      growth promoted by released GO-ER. Previous studies of pristine nanoparticles
      were unable to reflect the environmental effects of released nanoparticles into
      the environment, and our research on the exposure-toxicological continuum adds
      important contributions to this field.

PMID- 28437604
TI  - Antiplasmodial Mode of Action of Pantothenamides: Pantothenate Kinase Serves as a
      Metabolic Activator Not as a Target.
AB  - N-Substituted pantothenamides (PanAms) are pantothenate analogues with up to
      nanomolar potency against blood-stage Plasmodium falciparum (the most virulent
      species responsible for malaria). Although these compounds are known to target
      coenzyme A (CoA) biosynthesis and/or utilization, their exact mode of action
      (MoA) is still unknown. Importantly, PanAms that retain the natural beta-alanine
      moiety are more potent than other variants, consistent with the involvement of
      processes that are selective for pantothenate (the precursor of CoA) or its
      derivatives. The transport of pantothenate and its phosphorylation by P.
      falciparum pantothenate kinase (PfPanK, the first enzyme of CoA biosynthesis) are
      two such processes previously highlighted as potential targets for the PanAms'
      antiplasmodial action. In this study, we investigated the effect of PanAms on
      these processes using their radiolabeled versions (synthesized here for the first
      time), which made possible the direct measurement of PanAm uptake by isolated
      blood-stage parasites and PanAm phosphorylation by PfPanK present in parasite
      lysates. We found that the MoA of PanAms does not involve interference with
      pantothenate transport and that inhibition of PfPanK-mediated pantothenate
      phosphorylation does not correlate with PanAm antiplasmodial activity. Instead,
      PanAms that retain the beta-alanine moiety were found to be metabolically
      activated by PfPanK in a selective manner, forming phosphorylated products that
      likely inhibit other steps in CoA biosynthesis or are transformed into CoA
      antimetabolites that can interfere with CoA utilization. These findings provide
      direction for the ongoing development of CoA-targeted inhibitors as
      antiplasmodial agents with clinical potential.

PMID- 28437607
TI  - Real Cost of Speed: The Effect of a Time-Saving Multiple-Time-Stepping Algorithm
      on the Accuracy of Molecular Dynamics Simulations.
AB  - To enhance efficiency in molecular dynamics simulations, forces that vary slowly
      are often evaluated less often than those that vary rapidly. We show that the
      multiple-time-step algorithm implemented in recent versions of GROMACS results in
      significant differences in the collective properties of a system under conditions
      where the system was previously stable. The implications of changing the
      simulation algorithm without assessment of potential artifacts on the
      parametrization and transferability of effective force fields are discussed.

PMID- 28437606
TI  - Transfer Study of Silver Nanoparticles in Poultry Production.
AB  - Silver nanoparticles (AgNPs) are of interest due to their antimicrobial activity
      and are seen as potential candidates to replace antibiotics in animal husbandry.
      A few studies have focused on this new application, but they lack any
      considerations about residual accumulation of AgNPs in edible animal tissues and
      animal products. In this research, a 22 day in vivo study was carried out by oral
      administration of 20 nm spherical PVP coated AgNPs to hens. Six doses of
      approximately 1 mg kg-1 of AgNPs-PVP each were administered to animals throughout
      the experimentation. Atomic absorption spectroscopy (AAS) was used for
      quantitative determination of residual total Ag in different organs and matrices.
      The analyses showed that Ag accumulates in livers (concentration ranging from 141
      MUg kg-1 to 269 MUg kg-1) and yolks (concentration ranging from 20 MUg kg-1 to 49
      MUg kg-1) but not in muscles, kidneys, and albumen belonging to hens of the
      treated group (tG2). Ag was not detected in animals of the control group (uG1)
      (i.e., total Ag < LOD = 10 MUg kg-1). Single particle inductively coupled plasma
      mass spectrometry (spICP-MS) and scanning electron microscopy with energy
      dispersive X-ray detection (SEM-EDX) were employed to elucidate the presence of
      AgNPs in livers and yolks belonging to tG2 animals. spICP-MS highlighted that
      part of residual Ag found in livers (about 5-20%) is in NP form with an average
      dimension of approximately 20 nm. SEM-EDX technique confirmed the presence of
      AgNPs only in livers of treated animals. The results show that feeding AgNPs to
      hens may become a source of consumer exposure to AgNPs. As far as we know this is
      the first study showing transfer of AgNPs or reaction products thereof from
      animal feed to animal products.

PMID- 28437608
TI  - CRISPR-Cas9 Mediated DNA Unwinding Detected Using Site-Directed Spin Labeling.
AB  - The RNA-guided CRISPR-Cas9 nuclease has revolutionized genome engineering, yet
      its mechanism for DNA target selection is not fully understood. A crucial step in
      Cas9 target recognition involves unwinding of the DNA duplex to form a three
      stranded R-loop structure. Work reported here demonstrates direct detection of
      Cas9-mediated DNA unwinding by a combination of site-directed spin labeling and
      molecular dynamics simulations. The results support a model in which the unwound
      nontarget strand is stabilized by a positively charged patch located between the
      two nuclease domains of Cas9 and reveal uneven increases in flexibility along the
      unwound nontarget strand upon scissions of the DNA backbone. This work
      establishes the synergistic combination of spin-labeling and molecular dynamics
      to directly monitor Cas9-mediated DNA conformational changes and yields
      information on the target DNA in different stages of Cas9 function, thus
      advancing mechanistic understanding of CRISPR-Cas9 and aiding future
      technological development.

PMID- 28437609
TI  - Source and Biological Response of Biochar Organic Compounds Released into Water;
      Relationships with Bio-Oil Composition and Carbonization Degree.
AB  - Water-soluble organic compounds (WSOCs) were extracted from corn stalk biochar
      produced at increasing pyrolysis temperatures (350-650  degrees C) and from the
      corresponding vapors, collected as bio-oil. WSOCs were characterized by gas
      chromatography (semivolatile fraction), negative electron spray ionization high
      resolution mass spectrometry (hydrophilic fraction) and fluorescence
      spectroscopy. The pattern of semivolatile WSOCs in bio-oil was dominated by
      aromatic products from lignocellulose, while in biochar was featured by saturated
      carboxylic acids from hemi/cellulose and lipids with concentrations decreasing
      with decreasing H/C ratios. Hydrophilic species in poorly carbonized biochar
      resembled those in bio-oil, but the increasing charring intensity caused a marked
      reduction in the molecular complexity and degree of aromaticity. Differences in
      the fluorescence spectra were attributed to the predominance of fulvic acid-like
      structures in biochar and lignin-like moieties in bio-oil. The divergence between
      pyrolysis vapors and biochar in the distribution of WSOCs with increasing
      carbonization was explained by the hydrophobic carbonaceous matrix acting like a
      filter favoring the release into water of carboxylic and fulvic acid-like
      components. The formation of these structures was confirmed in biochar produced
      by pilot plant pyrolysis units. Biochar affected differently shoot and root
      length of cress seedlings in germination tests highlighting its complex role on
      plant growth.

PMID- 28437610
TI  - Long-Acting Release Formulation of Exendin-4 Based on Biomimetic Mineralization
      for Type 2 Diabetes Therapy.
AB  - Exendin-4 has been clinically exploited for treating type 2 diabetes, but the
      short circulation half-life and multiple daily injections limit its widespread
      application with respect to poor patient compliance, low efficacy, and high
      treatment cost. In this study, a potent long-acting release system based on
      biomimetic mineralization was constructed for biocompatible and sustained exendin
      4 delivery. Similar to natural biomineralization, exendin-4 can be mineralized to
      form nanosized mineral solids by means of the reaction between acidic amino acid
      residues and calcium ions in a supersaturated environment with negligible
      influence on peptide bioactivity. Mineralized exendin-4 particles may be
      spontaneously absorbed by a living body under physiologically supersaturated
      conditions, resulting in gradual dissociation and sustained drug release. In such
      a way, the glucose level of diabetic mice may be effectively controlled for a
      long period of time by mineralized exendin-4 without obvious side effects. We
      believe this biomimetic formulation can serve as a promising candidate for future
      clinical applications for type 2 diabetes therapies.

PMID- 28437611
TI  - Dynamical Insights into the Decomposition of 1,2-Dioxetane.
AB  - Chemiluminescence in 1,2-dioxetane occurs through a thermally activated
      decomposition reaction into two formaldehyde molecules. Both ground-state and
      nonadiabatic dynamics (including singlet excited states) of the decomposition
      reaction have been simulated, starting from the first O-O bond-breaking
      transition structure. The ground-state dissociation occurs between t = 30 fs and
      t = 140 fs. The so-called entropic trap leads to frustrated dissociations,
      postponing the decomposition reaction. Specific geometrical conditions are
      necessary for the trajectories to escape from the entropic trap and for
      dissociation to be possible. The singlet excited states participate as well in
      the trapping of the molecule: dissociation including the nonadiabatic transitions
      to singlet excited states now occurs from t = 30 fs to t = 250 fs and later.
      Specific regions of the seam of the S0/S1 conical intersections that would
      "retain" the molecule for longer on the excited state have been identified.

PMID- 28437612
TI  - Combinatorial Library Based on Restriction Enzyme-mediated Modular Assembly.
AB  - Combinatorial approaches in directed evolution were proven to be more efficient
      for exploring sequence space and innovating function of protein. Here, we
      presented the modular assembly of secondary structures (MASS) for constructing a
      combinatorial library. In this approach, secondary structure elements were
      extracted from natural existing protein. The common linkers were flanking
      secondary structure elements, and then secondary structure elements were digested
      by Hinf I restriction endonuclease that was used in the construction of
      combinatorial library for the first time. The digested DNA fragments were
      randomly ligated in the sense orientation, then in sequence to be amplified by
      PCR and transformation. This approach showed that different DNA fragments without
      homologous sequences could be randomly assembled to create significant sequence
      space. With the structure analysis of recombinants, it would be beneficial to the
      rational design, even to the design of protein de novo, and to evolve any genetic
      part or circuit.

PMID- 28437613
TI  - Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in
      Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals.
AB  - The role of bile salt export protein (BSEP) inhibition in drug-induced liver
      injury (DILI) has been investigated widely, while inhibition of the canalicular
      multidrug resistant protein 3 (MDR3) has received less attention. This
      transporter plays a pivotal role in secretion of phospholipids into bile and
      functions coordinately with BSEP to mediate the formation of bile acid-containing
      biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined
      across 125 drugs (70 of Most-DILI-concern and 55 of No-DILI-concern). Of these
      tested, 41% of Most-DILI-concern and 47% of No-DILI-concern drugs had MDR3 IC50
      values of <50 MUM. A better distinction across DILI classifications occurred when
      systemic exposure was considered where safety margins of 50-fold had low
      sensitivity (0.29), but high specificity (0.96). Analysis of physical chemical
      property space showed that basic compounds were twice as likely to be MDR3
      inhibitors as acids, neutrals, and zwitterions and that inhibitors were more
      likely to have polar surface area (PSA) values of <100 A2 and cPFLogD values
      between 1.5 and 5. These descriptors, with different cutoffs, also highlighted a
      group of compounds that shared dual potency as MDR3 and BSEP inhibitors. Nine
      drugs classified as Most-DILI-concern compounds (four withdrawn, four boxed
      warning, and one liver injury warning in their approved label) had intrinsic
      potency features of <20 MUM in both assays, thereby reinforcing the notion that
      multiple inhibitory mechanisms governing bile formation (bile acid and
      phospholipid efflux) may confer additional risk factors that play into more
      severe forms of DILI as shown by others for BSEP inhibitors combined with
      multidrug resistance-associated protein (MRP2, MRP3, MRP4) inhibitory properties.
      Avoiding physical property descriptors that highlight dual BSEP and MDR3
      inhibition or testing drug candidates for inhibition of multiple efflux
      transporters (e.g., BSEP, MDR3, and MRPs) may be an effective strategy for
      prioritizing drug candidates with less likelihood of causing clinical DILI.

PMID- 28437614
TI  - Engineering Highly Interconnected Neuronal Networks on Nanowire Scaffolds.
AB  - Identifying the specific role of physical guidance cues in the growth of neurons
      is crucial for understanding the fundamental biology of brain development and for
      designing scaffolds for tissue engineering. Here, we investigate the structural
      significance of nanoscale topographies as physical cues for neurite outgrowth and
      circuit formation by growing neurons on semiconductor nanowires. We monitored
      neurite growth using optical and scanning electron microscopy and evaluated the
      spontaneous neuronal network activity using functional calcium imaging. We show,
      for the first time, that an isotropic arrangement of indium phosphide (InP)
      nanowires can serve as physical cues for guiding neurite growth and aid in
      forming a network with neighboring neurons. Most importantly, we confirm that
      multiple neurons, with neurites guided by the topography of the InP nanowire
      scaffolds, exhibit synchronized calcium activity, implying intercellular
      communications via synaptic connections. Our study imparts new fundamental
      insights on the role of nanotopographical cues in the formation of functional
      neuronal circuits in the brain and will therefore advance the development of
      neuroprosthetic scaffolds.

PMID- 28437615
TI  - Experimental Demonstration of Feature Extraction and Dimensionality Reduction
      Using Memristor Networks.
AB  - Memristors have been considered as a leading candidate for a number of critical
      applications ranging from nonvolatile memory to non-Von Neumann computing
      systems. Feature extraction, which aims to transform input data from a high
      dimensional space to a space with fewer dimensions, is an important technique
      widely used in machine learning and pattern recognition applications. Here, we
      experimentally demonstrate that memristor arrays can be used to perform principal
      component analysis, one of the most commonly used feature extraction techniques,
      through online, unsupervised learning. Using Sanger's rule, that is, the
      generalized Hebbian algorithm, the principal components were obtained as the
      memristor conductances in the network after training. The network was then used
      to analyze sensory data from a standard breast cancer screening database with
      high classification success rate (97.1%).

PMID- 28437616
TI  - Neural Network and Nearest Neighbor Algorithms for Enhancing Sampling of
      Molecular Dynamics.
AB  - The free energy calculations of complex chemical and biological systems with
      molecular dynamics (MD) are inefficient due to multiple local minima separated by
      high-energy barriers. The minima can be escaped using an enhanced sampling method
      such as metadynamics, which apply bias (i.e., importance sampling) along a set of
      collective variables (CV), but the maximum number of CVs (or dimensions) is
      severely limited. We propose a high-dimensional bias potential method (NN2B)
      based on two machine learning algorithms: the nearest neighbor density estimator
      (NNDE) and the artificial neural network (ANN) for the bias potential
      approximation. The bias potential is constructed iteratively from short biased MD
      simulations accounting for correlation among CVs. Our method is capable of
      achieving ergodic sampling and calculating free energy of polypeptides with up to
      8-dimensional bias potential.

PMID- 28437617
TI  - Electrostatic Origin of the Red Solvatochromic Shift of DFHBDI in RNA Spinach.
AB  - Interactions with the environment tune the spectral properties of biological
      chromophores, e.g., fluorescent proteins. Understanding the relative contribution
      of the various types of noncovalent interactions in the spectral shifts can
      provide rational design principles toward developing new fluorescent probes. In
      this work, we investigate the origin of the red shift in the absorption spectra
      of the difluoro hydroxybenzylidene dimethyl imidazolinone (DFHBDI) chromophore in
      RNA spinach as compared to the aqueous solution. We systematically decompose the
      effects of various components of interactions, namely, stacking, hydrogen
      bonding, and long-range electrostatics, in order to elucidate the relative role
      of these interactions in the observed spectral behavior. We find that the
      absorption peak of DFHBDI is red-shifted by ~0.35 eV in RNA relative to the
      aqueous solution. Earlier proposals from Huang and co-workers have implicated the
      stacking interactions between DFHBDI and nucleic acid bases to be the driving
      force behind the observed red shift. In contrast, our findings reveal that the
      long-range electrostatic interactions between DFHBDI and negatively charged RNA
      make the most significant contribution. Moreover, we notice that the opposing
      electrostatic fields due to the RNA backbone and the polarized water molecules
      around the RNA give rise to the resultant red shift. Our results emphasize the
      effect of strong heterogeneity in the various environmental factors that might be
      competing with each other.

PMID- 28437618
TI  - State-of-the-Art Calculations of Sublimation Enthalpies for Selected Molecular
      Crystals and Their Computational Uncertainty.
AB  - A computational methodology for calculation of sublimation enthalpies of
      molecular crystals from first principles is developed and validated by comparison
      to critically evaluated literature experimental data. Temperature-dependent
      sublimation enthalpies for a set of selected 22 molecular crystals in their low
      temperature phases are calculated. The computational methodology consists of
      several building blocks based on high-level electronic structure methods of
      quantum chemistry and statistical thermodynamics. Ab initio methods up to the
      coupled clusters with iterative treatment of single and double excitations and
      perturbative triples correction with an estimated complete basis set description
      [CCSD(T)/CBS] are used to calculate the cohesive energies of crystalline phases
      within a fragment-based additive scheme. Density functional theory (DFT)
      calculations with periodic boundary conditions (PBC) coupled with the quasi
      harmonic approximation are used to evaluate the thermal contributions to the
      enthalpy of the solid phase. The properties of the vapor phase are calculated
      within the ideal-gas model using the rigid-rotor harmonic-oscillator model with
      correction for internal rotation using a one-dimensional hindered rotor
      approximation and a proper treatment of the molecular rotational degrees of
      freedom in the vicinity of 0 K. All individual terms contributing to the
      sublimation enthalpy as a function of temperature are discussed and their
      uncertainties estimated by comparison to critically evaluated experimental data.

PMID- 28437619
TI  - Management of Posterior Cruciate Ligament Tibial Avulsion Injuries: A Systematic
      Review.
AB  - BACKGROUND: Tibial-sided avulsion injuries of the posterior cruciate ligament
      (PCL) generally require surgical intervention. No consensus exists concerning the
      optimal surgical treatment approach for these injuries. PURPOSE: To perform a
      systematic review investigating the open and arthroscopic surgical treatment
      modalities, outcomes, and complications of PCL tibial-sided bony avulsions. STUDY
      DESIGN: Systematic review; Level of evidence, 4. METHODS: The authors performed a
      systematic review of the literature utilizing PubMed and EMBASE from 1975 to
      present outlining open versus arthroscopic surgical repair of PCL bony avulsion
      injuries and comparing subjective and objective postoperative patient-reported
      outcomes, including Tegner, IKDC (International Knee Documentation Committee),
      and Lysholm scoring systems, as well as rates of patient complications. The quest
      was performed in June 2016, and searched terms included posterior cruciate
      ligament, PCL, bony, avulsion(s), tibial-sided, open, and arthroscopic. Inclusion
      criteria included English-language studies involving surgical fixation strategies
      for PCL tibial-sided bony avulsions. Exclusion criteria included non-English
      language, case studies/case series, and subject matter not pertaining to PCL bony
      avulsions. RESULTS: Twenty-eight articles comprising 637 patients met the
      criteria and were included in the final review. PCL injuries with a tibial-sided
      avulsion were the result of motor vehicle accidents in 68.4% of patients, with
      59.0% of these injuries resulting from motorcycle accidents. The arthroscopic
      group had better IKDC grade A scores (78.9%), indicating a normal knee
      postoperatively, as compared with the open group (65.9%). The postoperative
      Lysholm scores were similar between the groups, with a mean of 95.0 in the
      arthroscopic group and 92.8 in the open group. The arthroscopic group also
      reported 100% return to preinjury level of activity, compared with 86.2% in the
      open group. The most common complication in both groups was arthrofibrosis, which
      was reported more often in the arthroscopic group (0%-35%) versus the open
      treatment group (0%-25%). CONCLUSION: In patients with displaced tibial-sided PCL
      avulsion fractures treated operatively, surgical approaches render similar
      outcomes and risks. While the arthroscopic group had somewhat higher subjective
      and objective knee outcome scores, it demonstrated a slightly higher rate of
      arthrofibrosis. The clear advantage of the arthroscopic approach is that
      concomitant intra-articular injuries seen on preoperative magnetic resonance
      imaging, such as meniscal tears or osteochondral loose fragments, can be
      addressed at the time of the index operation.

PMID- 28437620
TI  - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF
      ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF
      CARDIOVASCULAR DISEASE.
AB  - OBJECTIVE: The development of these guidelines is mandated by the American
      Association of Clinical Endocrinologists (AACE) Board of Directors and American
      College of Endocrinology (ACE) Board of Trustees and adheres with published AACE
      protocols for the standardized production of clinical practice guidelines (CPGs).
      METHODS: Recommendations are based on diligent reviews of the clinical evidence
      with transparent incorporation of subjective factors, according to established
      AACE/ACE guidelines for guidelines protocols. RESULTS: The Executive Summary of
      this document contains 87 recommendations of which 45 are Grade A (51.7%), 18 are
      Grade B (20.7%), 15 are Grade C (17.2%), and 9 (10.3%) are Grade D. These
      detailed, evidence-based recommendations allow for nuance-based clinical decision
      making that addresses multiple aspects of real-world medical care. The evidence
      base presented in the subsequent Appendix provides relevant supporting
      information for Executive Summary Recommendations. This update contains 695
      citations of which 203 (29.2 %) are EL 1 (strong), 137 (19.7%) are EL 2
      (intermediate), 119 (17.1%) are EL 3 (weak), and 236 (34.0%) are EL 4 (no
      clinical evidence). CONCLUSION: This CPG is a practical tool that
      endocrinologists, other health care professionals, health-related organizations,
      and regulatory bodies can use to reduce the risks and consequences of
      dyslipidemia. It provides guidance on screening, risk assessment, and treatment
      recommendations for a range of individuals with various lipid disorders. The
      recommendations emphasize the importance of treating low-density lipoprotein
      cholesterol (LDL-C) in some individuals to lower goals than previously endorsed
      and support the measurement of coronary artery calcium scores and inflammatory
      markers to help stratify risk. Special consideration is given to individuals with
      diabetes, familial hypercholesterolemia, women, and youth with dyslipidemia. Both
      clinical and cost-effectiveness data are provided to support treatment decisions.
      ABBREVIATIONS: 4S = Scandinavian Simvastatin Survival Study A1C = glycated
      hemoglobin AACE = American Association of Clinical Endocrinologists AAP =
      American Academy of Pediatrics ACC = American College of Cardiology ACE =
      American College of Endocrinology ACS = acute coronary syndrome ADMIT = Arterial
      Disease Multiple Intervention Trial ADVENT = Assessment of Diabetes Control and
      Evaluation of the Efficacy of Niaspan Trial AFCAPS/TexCAPS = Air Force/Texas
      Coronary Atherosclerosis Prevention Study AHA = American Heart Association AHRQ =
      Agency for Healthcare Research and Quality AIM-HIGH = Atherothrombosis
      Intervention in Metabolic Syndrome With Low HDL/High Triglycerides trial ASCVD =
      atherosclerotic cardiovascular disease ATP = Adult Treatment Panel apo =
      apolipoprotein BEL = best evidence level BIP = Bezafibrate Infarction Prevention
      trial BMI = body mass index CABG = coronary artery bypass graft CAC = coronary
      artery calcification CARDS = Collaborative Atorvastatin Diabetes Study CDP =
      Coronary Drug Project trial CI = confidence interval CIMT = carotid intimal media
      thickness CKD = chronic kidney disease CPG(s) = clinical practice guideline(s)
      CRP = C-reactive protein CTT = Cholesterol Treatment Trialists CV =
      cerebrovascular CVA = cerebrovascular accident EL = evidence level FH = familial
      hypercholesterolemia FIELD = Secondary Endpoints from the Fenofibrate
      Intervention and Event Lowering in Diabetes trial FOURIER = Further
      Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects With Elevated
      Risk trial HATS = HDL-Atherosclerosis Treatment Study HDL-C = high-density
      lipoprotein cholesterol HeFH = heterozygous familial hypercholesterolemia HHS =
      Helsinki Heart Study HIV = human immunodeficiency virus HoFH = homozygous
      familial hypercholesterolemia HPS = Heart Protection Study HPS2-THRIVE =
      Treatment of HDL to Reduce the Incidence of Vascular Events trial HR = hazard
      ratio HRT = hormone replacement therapy hsCRP = high-sensitivity CRP IMPROVE-IT =
      Improved Reduction of Outcomes: Vytorin Efficacy International Trial IRAS =
      Insulin Resistance Atherosclerosis Study JUPITER = Justification for the Use of
      Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin LDL
      C = low-density lipoprotein cholesterol Lp-PLA2 = lipoprotein-associated
      phospholipase A2 MACE = major cardiovascular events MESA = Multi-Ethnic Study of
      Atherosclerosis MetS = metabolic syndrome MI = myocardial infarction MRFIT =
      Multiple Risk Factor Intervention Trial NCEP = National Cholesterol Education
      Program NHLBI = National Heart, Lung, and Blood Institute PCOS = polycystic ovary
      syndrome PCSK9 = proprotein convertase subtilisin/kexin type 9 Post CABG = Post
      Coronary Artery Bypass Graft trial PROSPER = Prospective Study of Pravastatin in
      the Elderly at Risk trial QALY = quality-adjusted life-year ROC = receiver
      operator characteristic SOC = standard of care SHARP = Study of Heart and Renal
      Protection T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus TG =
      triglycerides TNT = Treating to New Targets trial VA-HIT = Veterans Affairs High
      Density Lipoprotein Cholesterol Intervention Trial VLDL-C = very low-density
      lipoprotein cholesterol WHI = Women's Health Initiative.

PMID- 28437621
TI  - C21 steroidal glycosides from Cynanchum auriculatum and their neuroprotective
      effects against H2O2-induced damage in PC12 cells.
AB  - Twenty-three undescribed previously C21 steroidal glycosides, named saccatols D-K
      and cynsaccatols I-W, together with six known analogs were isolated from the
      roots of Cynanchum auriculatum Royle ex Wight (Apocynaceae). Their structures
      were elucidated by a variety of spectroscopic techniques, as well as HRESIMS and
      GC method. All isolated compounds were tested their neuroprotective effects on
      the model of H2O2-induced damage to PC12 cells. Except saccatols D-F, J,
      cynsaccatol V and wilfoside A, other twenty-three isolates produced significantly
      activities against H2O2-induced cell damage (P < 0.001). Furthermore,
      cynsaccatols I, N, O and S can obvious inhibition of damaged PC12 cell apoptosis
      at their dosages of 1 MUM by Annexin V-FITC/PI double staining assay with flow
      cytometry.

PMID- 28437622
TI  - Sexually active bucks counterbalance the seasonal negative feedback of estradiol
      on LH in ovariectomized goats.
AB  - We showed previously that the permanent presence of bucks rendered sexually
      active by photoperiodic treatments, thereafter called photostimulated bucks,
      prevents the occurrence of seasonal anovulation; also, the introduction of these
      sexually active bucks induces ovulations during seasonal anestrus. Here, we
      studied the response of ovariectomized goats bearing 12-mm subcutaneous implants
      filled or not with estradiol to sexually active males to determine (1) whether
      the permanent presence of such bucks prevents the decrease of LH despite the
      presence of a negative feedback by estradiol mimicking that of seasonal anestrus
      (experiment 1) and (2) whether the introduction of photostimulated bucks
      increases the plasma LH concentrations in spite of this negative feedback
      (experiment 2). In experiment 1, one group of goats remained in contact with
      sexually active bucks, whereas the other group remained in contact with control
      bucks. Plasma LH concentrations were high and did not differ with time or between
      groups of females from November to February (P > 0.05), when both types of bucks
      were sexually active. Afterward, in goats in contact with control and sexually
      inactive bucks, LH concentrations decreased from March (P <= 0.01) and remained
      low until May, whereas LH levels remained high from March to May in goats in
      contact with the photostimulated bucks (P > 0.05). In experiment 2, 2 groups of
      females bearing empty subcutaneous implants, and 2 groups of goats bearing
      subcutaneous implants filled with estradiol, were exposed to control or
      photostimulated bucks. Plasma LH concentrations did not increase in goats bearing
      empty implants, when exposed to control or photostimulated bucks (from 2.01 +/-
      0.26 to 1.98 +/- 0.31 ng/mL, and from 2.45 +/- 0.29 to 2.42 +/- 0.21 ng/mL
      respectively; P > 0.05). In contrast, plasma LH concentrations increased from
      0.97 +/- 0.41 to 2.80 +/- 0.62 ng/mL in goats exposed to the photostimulated
      bucks and bearing estradiol implants (P < 0.05). Thus, the permanent presence of
      sexually active bucks prevented the decrease of plasma LH concentration in OVX +
      E2 goats during the seasonal anestrus, and the introduction of the
      photostimulated bucks increased the plasma LH concentrations in OVX + E2 goats
      during the seasonal anestrus. Therefore, we conclude that in both cases, the
      photostimulated bucks are able to reduce or counterbalance the seasonal negative
      feedback of estradiol on LH secretion.

PMID- 28437623
TI  - Selective scene perception deficits in a case of topographical disorientation.
AB  - Topographical disorientation (TD) is a neuropsychological condition characterized
      by an inability to find one's way, even in familiar environments. One common
      contributing cause of TD is landmark agnosia, a visual recognition impairment
      specific to scenes and landmarks. Although many cases of TD with landmark agnosia
      have been documented, little is known about the perceptual mechanisms which lead
      to selective deficits in recognizing scenes. In the present study, we test LH, a
      man who exhibits TD and landmark agnosia, on measures of scene perception that
      require selectively attending to either the configural or surface properties of a
      scene. Compared to healthy controls, LH demonstrates perceptual impairments when
      attending to the configuration of a scene, but not when attending to its surface
      properties, such as the pattern of the walls or whether the ground is sand or
      grass. In contrast, when focusing on objects instead of scenes, LH demonstrates
      intact perception of both geometric and surface properties. This study
      demonstrates that in a case of TD and landmark agnosia, the perceptual
      impairments are selective to the layout of scenes, providing insight into the
      mechanism of landmark agnosia and scene-selective perceptual processes.

PMID- 28437624
TI  - Immune response to Salmonella infections in vaccinated and non-vaccinated
      turkeys.
AB  - Vaccination has been widely used to reduce the Salmonella burden in poultry and
      subsequently the transmission to humans. Concerning turkey, there is little
      knowledge on the immune response to colonization and invasion by Salmonella
      species or about efficacy of vaccination and involved immune mechanisms. In the
      present study, turkeys were vaccinated at the day of hatch and infected with
      Salmonella Typhimurium (ST) or Enteritidis (SE) field strains three weeks later.
      A control group was kept uninfected. After challenge infection, bacterial counts
      in the cecal content, liver and spleen were determined 7 and 14days post
      infection. They were often statistically significantly lower in vaccinated poults
      than in non-vaccinated ones. Production of iNOS, and the cytokines IL-8, IL-10
      and IFN-gamma were reduced in vaccinated birds. However, neither the influx of
      CD4+, CD8alpha+ and CD28+ cells into cecal mucosa after infection nor the
      antibody response were statistically significantly altered in vaccinated birds.

PMID- 28437625
TI  - Imaging-guided synergetic therapy of orthotopic transplantation tumor by
      superselectively arterial administration of microwave-induced microcapsules.
AB  - It is an ambitious target to improve overall Hepatocellular Carcinoma therapeutic
      effects. Recently, MW ablation has emerged as a powerful thermal ablation
      technique, affording favorable survival with excellent local tumor control. To
      achieve better therapeutic effects of MW ablation, MW sensitizers are prepared
      for enhanced MW ablation to preferentially heat tumor territory. However, it is
      still not practicable for treatment of the orthotopic transplantation tumor.
      Herein, biocompatible and degradable methoxy poly(ethylene glycol)-poly(lactic-co
      glycolic acid) (mPEG-PLGA) microcapsules with hierarchical structure have been
      designed for microwave-induced tumor therapy. Chemical drug doxorubicin
      hydrochloride (DOX.HCl), microwave (MW) sensitizers and CT imaging contrast MoS2
      nanosheets and MR imaging contrast Fe3O4 nanoparticles are co-incorporated into
      the microcapsules. In vitro/vivo MR/CT dual-modal imaging results prove the
      potential application for guiding synergetic therapy and predicting post-therapy
      tumor progression in the orthotopic transplantation tumor model. After blocking
      the tumor-feeding arteries, these microcapsules not only exclude the cooling
      effect by cutting off the blood flow but also enhance MW heating conversion at
      tumor site. The focused MW heating makes microcapsules mollescent or ruptured and
      releases DOX.HCl from the microcapsules, achieving the controlled release of
      drugs for chemical therapy. Compared with MW ablation, 29.4% increase of necrosis
      diameter of normal liver in rabbit is obtained under MW ablation combined with
      transcatheter arterial blocking, and the average size of necrosis and inhibition
      rate of VX-2 liver orthotopic transplantation tumor in rabbit has increased by
      129.33% and 73.46%. Moreover, it is proved that the superselectively arterial
      administration of the as-prepared microcapsules has no recognizable toxicity on
      the animals. Therefore, this research provides a novel strategy for the
      construction of MW-induced microcapsules for orthotopic transplantation tumor
      ablation with the properties of MW sensitizing, superselective arterial blocking,
      control release and enhanced accumulation of DOX.HCl, and MR/CT dual-modal
      imaging, which exhibits great potential applications in the field of HCC therapy.

PMID- 28437626
TI  - Recent advances in CO2 bubble-generating carrier systems for localized controlled
      release.
AB  - This article reviews recent progress in the development of carbon dioxide (CO2)
      bubble-generating drug carriers, including their designs and operating
      mechanisms; these carriers constitute an advanced class of stimuli-responsive
      delivery systems with considerable potential. The drug carriers contain stimuli
      responsive agents, which are stable before they reach the target location, but
      enable rapid drug release that is triggered by the generation of CO2 bubbles,
      which are chemically inert, under certain stimuli. These CO2 bubble-generating
      carrier systems can be used to accumulate locally a delivered drug at the
      diseased tissue, while reducing side effects on the normal tissue, improving
      their therapeutic effectiveness. Since the generated CO2 bubbles are
      hyperechogenic, they may also be used as an ultrasound contrast agent in
      elucidating the status of the carriers and providing real-time diagnostic images.
      Perspectives of the future of applications of gases with therapeutic effects,
      such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), in
      such bubble-generating carrier systems, are also briefly discussed.

PMID- 28437627
TI  - Tumor acidity-activatable TAT targeted nanomedicine for enlarged
      fluorescence/magnetic resonance imaging-guided photodynamic therapy.
AB  - Nanoparticles simultaneously integrated the photosensitizers and diagnostic
      agents represent an emerging approach for imaging-guided photodynamic therapy
      (PDT). However, the diagnostic sensitivity and therapeutic efficacy of
      nanoparticles as well as the heterogeneity of tumors pose tremendous challenges
      for clinical imaging-guided PDT treatment. Herein, a polymeric nanoparticle with
      tumor acidity (pHe)-activatable TAT targeting ligand that encapsulates the
      photosensitizer chlorin e6 (Ce6) and chelates contrast agent Gd3+ is successfully
      developed for fluorescence/magnetic resonance (MR) dual-model imaging-guided
      precision PDT. We show clear evidence that the resulting nanoparticle DATAT-NP
      [its TAT lysine residues' amines was modified by 2,3-dimethylmaleic anhydride
      (DA)] efficiently avoids the rapid clearance by reticuloendothelial system (RES)
      by masking of the TAT peptide, resulting in the significantly prolonged
      circulation time in the blood. Once accumulating in the tumor tissues, DATAT-NP
      is reactivated by tumor acidity to promote cellular uptake, resulting in enlarged
      fluorescence/MR imaging signal intensity and elevated in vivo PDT therapeutic
      effect. This concept provides new avenues to design tumor acidity-activatable
      targeted nanoparticles for imaging-guided cancer therapy.

PMID- 28437628
TI  - Advanced biomaterials and microengineering technologies to recapitulate the
      stepwise process of cancer metastasis.
AB  - Cancer is one of the leading causes of death globally according to the World
      Health Organization. Although improved treatments and early diagnoses have
      reduced cancer related mortalities, metastatic disease remains a major clinical
      challenge. The local tumor microenvironment plays a significant role in cancer
      metastasis, where tumor cells respond and adapt to a plethora of biochemical and
      biophysical signals from stromal cells and extracellular matrix (ECM) proteins.
      Due to these complexities, there is a critical need to understand molecular
      mechanisms underlying cancer metastasis to facilitate the discovery of more
      effective therapies. In the past few years, the integration of advanced
      biomaterials and microengineering approaches has initiated the development of
      innovative platform technologies for cancer research. These technologies enable
      the creation of biomimetic in vitro models with physiologically relevant (i.e. in
      vivo-like) characteristics to conduct studies ranging from fundamental cancer
      biology to high-throughput drug screening. In this review article, we discuss the
      biological significance of each step of the metastatic cascade and provide a
      broad overview on recent progress to recapitulate these stages using advanced
      biomaterials and microengineered technologies. In each section, we will highlight
      the advantages and shortcomings of each approach and provide our perspectives on
      future directions.

PMID- 28437629
TI  - Design and development of benzoxazole derivatives with toll-like receptor 9
      antagonism.
AB  - Toll-like receptor 9 (TLR9) is a major therapeutic target for numerous
      inflammatory disorders. Development of small molecule inhibitors for TLR9 remains
      largely empirical due to lack of structural understanding of potential TLR9
      antagonism by small molecules and due to the unusual topology of the ligand
      binding surface of the receptor. To develop a structural model for rational
      design of small molecule TLR9 antagonists, an enhanced homology model of human
      TLR9 (hTLR9) was constructed. Binding mode analysis of a series of molecules
      having characteristic molecular geometry, flexibility and basicity was conducted
      based on crystal structure of the inhibitory DNA (iDNA) bound to horse and bovine
      TLR9. Interaction with specific amino acid residues in four leucine rich repeat
      (LRR) regions of TLR9 was identified to be critical for antagonism by small
      molecules. The biological validation of TLR9 antagonism and its correlation with
      probe-receptor interactions led to a reliable model that could be used for
      development of novel small molecules with potent TLR9 antagonism (IC50 30-100 nM)
      with excellent selectivity against TLR7.

PMID- 28437630
TI  - Modified natural cycle for embryo transfer using frozen-thawed blastocysts: A
      satisfactory option.
AB  - OBJECTIVE: To describe pregnancy outcomes of frozen-thawed blastocysts cycles
      using modified natural cycle frozen embryo transfers (NC-FET) and down-regulated
      hormonally controlled frozen embryo transfers (HC-FET) protocols. STUDY DESIGN:
      This retrospective cohort study included all patients undergoing either modified
      NC-FET or down-regulated HC-FET using frozen-thawed day 5 embryos. Cycles with
      donor blastocysts were excluded. Four hundred twenty eight patients underwent a
      total of 493 FET cycles. Patients with regular menses and evidence of ovulation
      underwent modified NC-FET. These patients were given hCG 10,000 IU IM on the day
      of LH-surge. Vaginal progesterone (P4) was started two days later and blastocyst
      transfer was planned seven days after detecting the LH surge. Anovulatory
      patients and some ovulatory patients underwent down-regulated HC-FET. These
      patients were placed on medroxy-progesterone acetate (10mg) for 10days to bring
      on menses and were also given a half-dose of GnRH-agonist (GnRH-a) on the third
      day of medroxy-progesterone acetate. Exogenous estradiol was initiated on the
      third day of menses. Once serum E2 levels reached >500pg/mL and endometrial
      lining reached >8mm, intramuscular (IM) P4 in oil was administered. Blastocyst
      FET was planned 6days after initiating P4. The primary outcomes included clinical
      pregnancy and delivery rates. RESULTS: There were 197 patients in the modified NC
      FET protocol and 181 in the down-regulated HC-FET protocol. Mean age (years), day
      3 FSH levels (mIU/mL) and percentage of patients with male factor infertility
      were significantly higher and mean BMI (kg/m2) was significantly lower in
      modified NC-FET compared to HC-FET, respectively. Analysis of the first cycle
      pregnancy outcomes revealed no significant differences in clinical pregnancy rate
      (54.3% vs. 52.5%) and delivery rate (47.2% vs. 43.6%) between modified NC-FET and
      HC-FET. Logistic regression analysis showed age (OR=0.939, 95% CI 0.894-0.989,
      p=0.011), number of blastocysts transferred (OR=1.414, 95% CI 1.046-1.909,
      p=0.024), and the year of FET (OR=1.127, 95% CI 1.029-1.234, p=0.010) were
      significant factors impacting clinical pregnancy. An age analysis within three
      age groups (<=35, 36-39, >=40) was performed, but no significant difference in
      clinical pregnancy was observed. CONCLUSION: Our data suggests that modified NC
      FET protocol has comparable pregnancy outcomes to down-regulated HC-FET when
      utilizing frozen-thawed day 5 embryos.

PMID- 28437631
TI  - Age-independent anti-Mullerian hormone (AMH) standard deviation scores to
      estimate ovarian function.
AB  - OBJECTIVIES: To determine single year age-specific anti-Mullerian hormone (AMH)
      standard deviation scores (SDS) for women associated to normal ovarian function
      and different ovarian disorders resulting in sub- or infertility. DESIGN AND
      METHODS: Determination of particular year median and mean AMH values with
      standard deviations (SD), calculation of age-independent cut off SDS for the
      discrimination between normal ovarian function and ovarian disorders. RESULTS:
      Single-year-specific median, mean, and SD values have been evaluated for the
      Beckman Access AMH immunoassay. While the decrease of both median and mean AMH
      values is strongly correlated with increasing age, calculated SDS values have
      been shown to be age independent with the differentiation between normal ovarian
      function measured as occurred ovulation with sufficient luteal activity compared
      with hyperandrogenemic cycle disorders or anovulation associated with high AMH
      values and reduced ovarian activity or insufficiency associated with low AMH,
      respectively. CONCLUSION: These results will be helpful for the treatment of
      patients and the ventilation of the different reproductive options.

PMID- 28437632
TI  - BGCS uterine cancer guidelines: Recommendations for practice.
AB  - The British Gynaecological Cancer Society has issued the first Endometrial
      (Uterine) Cancer guidelines as recommendation for practice for the UK.

PMID- 28437633
TI  - MicroRNA-500a promotes migration and invasion in hepatocellular carcinoma by
      activating the Wnt/beta-catenin signaling pathway.
AB  - Increased expression of microRNA-500a (miR-500a) has been reported in the serum
      of hepatocellular carcinoma (HCC) patients. However, the biological effects and
      mechanisms of miR-500a in hepatoma cells remain unclear. In this study, we found
      that miR-500a expression was up-regulated in HCC cell lines and tissues, and that
      high levels of miR-500a was associated with poor prognosis. We found that miR
      500a upregulation promoted migration and invasion in two hepatoma cell lines,
      HCCLM3 and SMMC7721, while miR-500a downregulation had the opposite effect. We
      demonstrated that miR-500a activates the Wnt/beta-catenin signaling pathway by
      directly binding to the 3'-untranslated region (UTR) of SFRP2 and GSK-3beta mRNA.
      In conclusion, our results indicate miR-500a promotes HCC migration and invasion
      through activating Wnt/beta-catenin signaling by directly binding to SFPR2 and
      GSK-3beta.

PMID- 28437634
TI  - Convolutional neural network regression for short-axis left ventricle
      segmentation in cardiac cine MR sequences.
AB  - Automated left ventricular (LV) segmentation is crucial for efficient
      quantification of cardiac function and morphology to aid subsequent management of
      cardiac pathologies. In this paper, we parameterize the complete (all short axis
      slices and phases) LV segmentation task in terms of the radial distances between
      the LV centerpoint and the endo- and epicardial contours in polar space. We then
      utilize convolutional neural network regression to infer these parameters.
      Utilizing parameter regression, as opposed to conventional pixel classification,
      allows the network to inherently reflect domain-specific physical constraints. We
      have benchmarked our approach primarily against the publicly-available left
      ventricle segmentation challenge (LVSC) dataset, which consists of 100 training
      and 100 validation cardiac MRI cases representing a heterogeneous mix of cardiac
      pathologies and imaging parameters across multiple centers. Our approach attained
      a .77 Jaccard index, which is the highest published overall result in comparison
      to other automated algorithms. To test general applicability, we also evaluated
      against the Kaggle Second Annual Data Science Bowl, where the evaluation metric
      was the indirect clinical measures of LV volume rather than direct myocardial
      contours. Our approach attained a Continuous Ranked Probability Score (CRPS) of
      .0124, which would have ranked tenth in the original challenge. With this we
      demonstrate the effectiveness of convolutional neural network regression paired
      with domain-specific features in clinical segmentation.

PMID- 28437635
TI  - Three cysteine residues of SLC52A1, a receptor for the porcine endogenous
      retrovirus-A (PERV-A), play a critical role in cell surface expression and
      infectivity.
AB  - Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells
      in vitro, thus raising the potential risk of cross-species transmission in
      xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and
      SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding
      SLC52A1 identified that only one of two putative glycosylation signals is
      occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not
      necessary for PERV-A receptor function. We also identified that at a minimum,
      three cysteine residues are sufficient for SLC52A1 cell surface expression.
      Mutation of cysteine at position 365 and either of the two cysteine residues in
      the C-terminal tail at positions 442 or 446 reduced SLC52A1 surface expression
      and PERV-A infection suggesting that these residues may contribute to overall
      structural stability and receptor function. Understanding interactions between
      PERV-A and its cellular receptor may provide novel strategies to prevent zoonotic
      infection in the setting of xenotransplantation.

PMID- 28437636
TI  - Chimeric Flock House virus protein A with endoplasmic reticulum-targeting domain
      enhances viral replication and virus-like particle trans-encapsidation in plants.
AB  - Flock House virus (FHV) RNA can be trans-encapsidated, entirely in planta, by
      tobacco mosaic virus coat protein to form virus-like particles (VLPs).
      Vaccination with these VLPs leads to strong antigen expression in mice and immune
      activation. We hypothesize that creating an additional cellular site for
      replication and/or trans-encapsidation might significantly improve the final
      output of trans-encapsidated product. FHV protein A was engineered to target the
      endoplasmic reticulum (ER) via a heterologous tobacco etch virus ER-targeting
      domain, and was expressed in cis or in trans relative to the replicating FHV
      RNA1. A strong increase in marker gene expression in plants was noted when ER
      targeted protein A was supplied in trans. RNA fluorescence in situ hybridization
      revealed RNA1 replication in both the mitochondria and ER, and total RNA1
      accumulation was increased. In support of our hypothesis, VLP yield was increased
      significantly by the addition of this single genetic component to the inoculum.

PMID- 28437637
TI  - Analysis of free moment and center of pressure frequency components during quiet
      standing using magnitude squared coherence.
AB  - To date, no postural studies have investigated the specific relationship between
      linear (anteroposterior (AP) and mediolateral (ML)) postural sway and the free
      moment (FM) over the range of biomechanically important frequencies. The goal of
      the current paper is to study the relationship between FM and the AP/ML movements
      during quiet standing with respect to individual frequencies. Mean squared
      coherence, which measures the degree of the relationship between two signals as a
      function of frequency, is employed to address this question. The results showed
      that, in two conditions (eyes opened and eyes closed), at very low frequencies
      (<0.5Hz), AP and FM were strongly correlated (>0.8) while there was a weak
      correlation between ML and FM (~0.2). The situation reversed from (0.5 to 1.5Hz),
      with AP/FM correlation decreasing, and ML/FM correlation peaking slightly below
      1.0Hz. Both conditions were only weakly correlated beyond 1.5Hz. It is suggested
      that these observations arise from differences in ankle activation between the
      left and right sides, whereas at higher frequencies, high coherence between ML
      and FM is a hip control strategy.

PMID- 28437638
TI  - Motor expertise and performance in spatial tasks: A meta-analysis.
AB  - The present study aimed to provide a summary of findings relevant to the
      influence of motor expertise on performance in spatial tasks and to examine
      potential moderators of this effect. Studies of relevance were those in which
      individuals involved in activities presumed to require motor expertise were
      compared to non-experts in such activities. A final set of 62 effect sizes from
      33 samples was included in a multilevel meta-analysis. The results showed an
      overall advantage in favor of motor experts in spatial tasks (d=0.38). However,
      the magnitude of that effect was moderated by expert type (athlete, open
      skills/ball sports, runner/cyclist, gymnast/dancers, musicians), stimulus type
      (2D, blocks, bodies, others), test category (mental rotation, spatial perception,
      spatial visualization), specific test (Mental Rotations Test, generic mental
      rotation, disembedding, rod-and-frame test, other), and publication status. These
      findings are discussed in the context of embodied cognition and the potential
      role of activities requiring motor expertise in promoting good spatial
      performance.

PMID- 28437639
TI  - A novel biosensor based on boronic acid functionalized metal-organic frameworks
      for the determination of hydrogen peroxide released from living cells.
AB  - In this work, we report a durable and sensitive H2O2 biosensor based on boronic
      acid functionalized metal-organic frameworks (denoted as MIL-100(Cr)-B) as an
      efficient immobilization matrix of horseradish peroxidase (HRP). MIL-100(Cr)-B
      features a hierarchical porous structure, extremely high surface area, and
      sufficient recognition sites, which can significantly increase HRP loading and
      prevent them from leakage and deactivation. The H2O2 biosensor can be easily
      achieved without any complex processing. Meanwhile, the immobilized HRP exhibited
      enhanced stability and remarkable catalytic activity towards H2O2 reduction.
      Under optimal conditions, the biosensor showed a fast response time (less than
      4s) to H2O2 in a wide linear range of 0.5-3000MUM with a low detection limit of
      0.1MUM, as well as good anti-interference ability and long-term storage
      stability. These excellent performances substantially enable the proposed
      biosensor to be used for the real-time detection of H2O2 released from living
      cells with satisfactory results, thus showing the potential application in the
      study of H2O2-involved dynamic pathological and physiological process.

PMID- 28437640
TI  - The woven fiber organic electrochemical transistors based on polypyrrole
      nanowires/reduced graphene oxide composites for glucose sensing.
AB  - Novel woven fiber organic electrochemical transistors based on polypyrrole (PPy)
      nanowires and reduced graphene oxide (rGO) have been prepared. SEM revealed that
      the introduction of rGO nanosheets could induce the growth and increase the
      amount of PPy nanowires. Moreover, it could enhance the electrical performance of
      fiber transistors. The hybrid transistors showed high on/off ratio of 102, fast
      switch speed, and long cycling stability. The glucose sensors based on the fiber
      organic electrochemical transistors have also been investigated, which exhibited
      outstanding sensitivity, as high as 0.773 NCR/decade, with a response time as
      fast as 0.5s, a linear range of 1nM to 5MUM, a low detection concentration as
      well as good repeatability. In addition, the glucose could be selectively
      detected in the presence of ascorbic acid and uric acid interferences. The
      reliability of the proposed glucose sensor was evaluated in real samples of
      rabbit blood. All the results indicate that the novel fiber transistors pave the
      way for portable and wearable electronics devices, which have a promising future
      for healthcare and biological applications.

PMID- 28437641
TI  - Human neuronal cell based assay: A new in vitro model for toxicity evaluation of
      ciguatoxin.
AB  - Ciguatoxins (CTXs) are emerging marine neurotoxins representing the main cause of
      ciguatera fish poisoning, an intoxication syndrome which configures a health
      emergency and constitutes an evolving issue constantly changing due to new
      vectors and derivatives of CTXs, as well as their presence in new non-endemic
      areas. The study applied the neuroblastoma cell model of human origin (SH-SY5Y)
      to evaluate species-specific mechanistic information on CTX toxicity. Metabolic
      functionality, cell morphology, cytosolic Ca2+i responses, neuronal cell growth
      and proliferation were assessed after short- (4-24h) and long-term exposure
      (10days) to P-CTX-3C. In SH-SY5Y, P-CTX-3C displayed a powerful cytotoxicity
      requiring the presence of both Veratridine and Ouabain. SH-SY5Y were very
      sensitive to Ouabain: 10 and 0.25nM appeared the optimal concentrations, for
      short- and long-term toxicity studies, respectively, to be used in co-incubation
      with Veratridine (25MUM), simulating the physiological and pathological
      endogenous Ouabain levels in humans. P-CTX-3C cytotoxic effect, on human neurons
      co-incubated with OV (Ouabain+Veratridine) mix, was expressed starting from 100pM
      after short- and 25pM after long-term exposure. Notably, P-CTX-3C alone at 25nM
      induced cytotoxicity after 24h and prolonged exposure. This human brain-derived
      cell line appears a suitable cell-based-model to evaluate cytotoxicity of CTX
      present in marine food contaminated at low toxic levels and to characterize the
      toxicological profile of other/new congeners.

PMID- 28437643
TI  - A co-production of sugars, lignosulfonates, cellulose, and cellulose nanocrystals
      from ball-milled woods.
AB  - This study demonstrated the technical potential for the large-scale co-production
      of sugars, lignosulfonates, cellulose, and cellulose nanocrystals. Ball-milled
      woods with two particle sizes were prepared by ball milling for 80min or 120min
      (BMW80, BMW120) and then enzymatically hydrolyzed. 78.3% cellulose conversion of
      BMW120 was achieved, which was three times as high as the conversion of BMW80.
      The hydrolyzed residues (HRs) were neutrally sulfonated cooking. 57.72g/L and
      88.16g/L lignosulfonate concentration, respectively, were harvested from HR80 and
      HR120, and 42.6+/-0.5% lignin were removed. The subsequent solid residuals were
      purified to produce cellulose and then this material was acid-hydrolyzed to
      produce cellulose nanocrystals. The BMW120 maintained smaller particle size and
      aspect ratio during each step of during the multiple processes, while the average
      aspect ratio of its cellulose nanocrystals was larger. The crystallinity of both
      materials increased with each step of wet processing, reaching to 74% for the
      cellulose.

PMID- 28437642
TI  - Pentoses and light intensity increase the growth and carbohydrate production and
      alter the protein profile of Chlorella minutissima.
AB  - High concentrations of carbon, which is considered a necessary element, are
      required for microalgal growth. Therefore, the identification of alternative
      carbon sources available in large quantities is increasingly important. This
      study evaluated the effects of light variation and pentose addition on the
      carbohydrate content and protein profile of Chlorella minutissima grown in a
      raceway photobioreactor. The kinetic parameters, carbohydrate content, and
      protein profile of Chlorella minutissima and its theoretical potential for
      ethanol production were estimated. The highest cellular concentrations were
      obtained with a light intensity of 33.75umol.m-2.s-1. Arabinose addition combined
      with a light intensity of 33.75umol.m-2.s-1 increased the carbohydrate content by
      53.8% and theoretically produced 39.1mL.100g-1 ethanol. All of the assays showed
      that a lower light availability altered the protein profile. The luminous
      intensity affects xylose and arabinose assimilation and augments the carbohydrate
      content in C. minutissima, making this microalga appropriate for bioethanol
      production.

PMID- 28437644
TI  - Substrate inhibition and concentration control in an UASB-Anammox process.
AB  - An UASB-Anammox reactor was operated for more than one year to study the process
      performance variations respond to the nitrogen loading rate (NLR) and substrate
      concentration. The IC10 (451.1mg/L), IC50 (725.3mg/L) and the prospected
      threshold of influent total nitrogen (TN) concentration were simulated. A stable
      TN removal efficiency was obtained when the TN influent was controlled. The
      disequilibrium distribution of the substrate following the plug flow with the
      height of the reactor resulted in significant variations in specific Anammox
      activity from the bottom to the top of the reactor (348->3mgN/gVSS/d). With long
      term acclimation, the nitrogen removal capacity of Anammox sludge varied
      significantly, with the most activated sludge obtained in the bottom part a 100
      times capacity greater than that of the top. A stable performance with high
      removal efficiency in the constructed UASB-Anammox reactor was obtained when the
      influent TN concentration was below 451.1mg/L.

PMID- 28437645
TI  - Facile modification of nanoscale zero-valent iron with high stability for Cr(VI)
      remediation.
AB  - In this study, a highly stable nanoscale zero-valent iron composite (HS-NZVI) was
      obtained via modifying nanoscale zero-valent iron (NZVI) with tetraethyl
      orthosilicate (TEOS) and hexadecyltrimethoxysilane (HDTMOS), and used for Cr(VI)
      remediation in aqueous solution. The obtained HS-NZVI remained stable in water
      without being oxidized for over 12h. After four consecutive runs, the Cr(VI)
      removal efficiency of HS-NZVI maintained a value of more than 82%. Moreover, the
      Cr(VI) removal capacity per unit weight of NZVI in HS-NZVI reached 292.8mg/g
      within 60min at the initial Cr(VI) concentration of 120mg/L at pH5. The Cr(VI)
      removal efficiency of HS-NZVI increased with decreasing solution pH, and the
      experimental data for Cr(VI) removal by HS-NZVI were well-described by the pseudo
      first-order reaction model. Additionally, scanning electron microscope (SEM)
      images, X-ray diffraction (XRD) patterns and X-ray photoelectron spectroscopy
      (XPS) measurements of the product after reaction revealed that the mechanism of
      Cr(VI) remediation by HS-NZVI mainly involved adsorption, reduction and co
      precipitation. Considering the advantages of easy preparation, excellent
      stability and reusability, and high Cr(VI) removal capacity as well as the
      magnetic recovery property, HS-NZVI is expected to have notably promising
      applications for the remediation of Cr(VI) contaminated sites.

PMID- 28437646
TI  - Combined effects of climate, restoration measures and slope position in change in
      soil chemical properties and nutrient loss across lands affected by the Wenchuan
      Earthquake in China.
AB  - The MS 8.0Wenchuan Earthquake in 2008 caused huge damage to land cover in the
      northwest of China's Sichuan province. In order to determine the nutrient loss
      and short term characteristics of change in soil chemical properties, we
      established an experiment with three treatments ('undestroyed', 'destroyed and
      treated', and 'destroyed and untreated'), two climate types (semi-arid hot
      climate and subtropical monsoon climate), and three slope positions (upslope, mid
      slope, and bottom-slope) in 2011. Ten soil properties-including pH, organic
      carbon, total nitrogen, total phosphorus, total potassium, Ca2+, Mg2+, alkaline
      hydrolysable nitrogen, available phosphorus, and available potassium-were
      measured in surface soil samples in December 2014. Analyses were performed to
      compare the characteristics of 3-year change in soil chemical properties in two
      climate zones. This study revealed that soil organic carbon, total nitrogen, Ca2+
      content, alkaline hydrolysable nitrogen, available phosphorus, and available
      potassium were significantly higher in subtropical monsoon climate zones than in
      semi-arid hot climate zones. However, subtropical monsoon climate zones had a
      higher decrease in soil organic carbon, total nitrogen, total phosphorus, total
      potassium, and alkaline hydrolysable nitrogen in 'destroyed and untreated' sites
      than in semi-arid hot climate zones. Most soil chemical properties exhibited
      significant interactions, indicating that they may degrade or develop
      concomitantly. 'Destroyed and treated' sites in both climate types had lower C:P
      and N:P ratios than 'destroyed and untreated' sites. Principal component analysis
      (PCA) showed that the first, second, and third principal components explained
      76.53% of the variation and might be interpreted as structural integrity,
      nutrient supply availability, and efficiency of soil; the difference of soil
      parent material; as well as weathering and leaching effects. Our study indicated
      that the characteristics of short term change in soil properties were affected by
      climate types and treatments, but not slope positions. Our results provide useful
      information for the selection of restoration countermeasures in different climate
      types to facilitate ecological restoration and reconstruction strategies in
      earthquake-affected areas.

PMID- 28437647
TI  - Comparison of landfarming amendments to improve bioremediation of petroleum
      hydrocarbons in Niger Delta soils.
AB  - Large scale landfarming experiments, using an extensive range of treatments, were
      conducted in the Niger-Delta, Nigeria to study the degradation of oil in
      contaminated soils. In this work the effect of nutrient addition, biosurfactant,
      Eisenia fetida (earthworm) enzyme extract, bulking and sorption agents and soil
      neutralization were tested. It was found that these treatments were successful in
      removing up to 53% of the total petroleum hydrocarbon in the soil within 16
      weeks. A comparison between treatments demonstrated that most were no more
      effective than agricultural fertilizer addition alone. One strategy that did show
      better performance was a combination of nutrients, biochar and biosurfactant,
      which was found to remove 23% more Total Petroleum Hydrocarbons (TPH) than
      fertilizer alone. However, when performance normalized costs were considered,
      this treatment became less attractive as a remedial option. Based on this same
      analysis it was concluded that fertilizer only was the most cost effective
      treatment. As a consequence, it is recommended that fertilizer is used to enhance
      the landfarming of hydrocarbon contaminated soils in the Niger Delta. The
      attenuation rates of both bulk TPH and Total Petroleum Hydrocarbon Criteria
      Working Group (TPHCWG) fractions are also provided. These values represent one of
      the first large scale and scientifically tested datasets for treatment of
      contaminated soil in the Niger Delta region. An inverse correlation between
      attenuation rates and hydrocarbon molecular weight was observed with heavy
      fractions showing much slower degradation rates than lighter fractions. Despite
      this difference, the bioremediation process resulted in significant removal of
      all TPH compounds independent of carbon number.

PMID- 28437648
TI  - Assessing soil-air partitioning of PAHs and PCBs with a new fugacity passive
      sampler.
AB  - : Soil-air fluxes of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated
      biphenyls (PCBs) were determined using a novel application of passive samplers to
      measure air and soil air, which is air in close proximity and in equilibrium with
      soil. Existing methods to measure flux of semi-volatile compounds between soil
      and air require collecting samples from the top soil layer. Yet, the top soil
      layer is hard to define and oversampling may misrepresent the exchangeable
      fraction. Alternatively, modified active samplers can measure soil air in situ,
      but require electricity while deployed. We present a new method to measure time
      weighted averages of soil air concentrations in situ using passive sampling and
      requiring no electricity: a box is placed over low-density polyethylene passive
      samplers deployed 1cm above the soil. Passive air samplers were also co-deployed
      1.5m above the soil to measure ambient air concentrations in three U.S.
      LOCATIONS: near a former PCB manufacturing facility in Anniston, Alabama; on a
      former creosoting and the current Wyckoff/Eagle Superfund site near Seattle,
      Washington; and near the site of a recent oil-train derailment and fire in
      Mosier, Oregon. Following n-hexane extraction, sampler extracts were analyzed for
      PAHs with gas chromatography-tandem mass spectrometry and PCBs with dual gas
      chromatography-electron capture detectors. PAHs were generally depositing at
      Anniston and Mosier sites, but volatilizing from soil in Wyckoff, the site with
      historically-contaminated soil. PCBs were detected most frequently at the
      Anniston site, although levels were lower than previous reports. Variability in
      concentration measurements was greater among soil air samplers than air samplers,
      likely due to soil heterogeneity. Environmental conditions under the novel soil
      air box did not substantially change soil-air partitioning behavior. This method
      of measuring soil air in situ will allow for understanding of source-sink
      dynamics at sites with recent and historical contamination, and where
      conventional sampling is challenging.

PMID- 28437649
TI  - Occurrences and removal of pharmaceuticals and personal care products (PPCPs) in
      drinking water and water/sewage treatment plants: A review.
AB  - In recent years, many of micropollutants have been widely detected because of
      continuous input of pharmaceuticals and personal care products (PPCPs) into the
      environment and newly developed state-of-the-art analytical methods. PPCP
      residues are frequently detected in drinking water sources, sewage treatment
      plants (STPs), and water treatment plants (WTPs) due to their universal
      consumption, low human metabolic capability, and improper disposal. When
      partially metabolized PPCPs are transferred into STPs, they elicit negative
      effects on biological treatment processes; therefore, conventional STPs are
      insufficient when it comes to PPCP removal. Furthermore, the excreted metabolites
      may become secondary pollutants and can be further modified in receiving water
      bodies. Several advanced treatment systems, including membrane filtration,
      granular activated carbon, and advanced oxidation processes, have been used for
      the effective removal of individual PPCPs. This review covers the occurrence
      patterns of PPCPs in water environments and the techniques adopted for their
      treatment in STP/WTP unit processes operating in various countries. The aim of
      this review is to provide a comprehensive summary of the removal and fate of
      PPCPs in different treatment facilities as well as the optimum methods for their
      elimination in STP and WTP systems.

PMID- 28437650
TI  - Indoor-to-outdoor relationship of aerosol particles inside a naturally ventilated
      apartment - A comparison between single-parameter analysis and indoor aerosol
      model simulation.
AB  - The indoor-to-outdoor relationship of aerosol particles is affected by several
      mechanisms including penetration, ventilation rate, dry deposition rate and
      sources. Understanding the effect of these factors is essential for a deeper
      knowledge of the indoor-to-outdoor relationship. In real-life conditions, it is
      difficult to analyze these factors in a naturally ventilated environment. In this
      study, a naturally ventilated and an occupied apartment was used to investigate
      the indoor-to-outdoor relationship of aerosol particles by applying two different
      techniques; single-parameter analysis and indoor aerosol model simulation. The
      indoor aerosol model simulation approach can describe the effect of these factors
      based on high time-resolution calculations and it is a powerful and robust
      approach. Single parameter analysis is very simple to apply but it is valid under
      certain conditions. In the absence of indoor activities (i.e. nighttime) and
      based on the particle number concentrations, the I/O ratio was <1 during spring
      but ~1.2 during winter. Based on the indoor aerosol model simulation results for
      the coarse fraction, the penetration factor (P) was 0.3-1, the ventilation rate
      (lambda) was 0.1-2h-1, and the deposition rate (lambdad) was ~0.15h-1. The coarse
      particles concentration was strongly affected by indoor activities. During
      extreme mechanical activities (e.g. vacuum cleaning), the concentration increased
      by a factor of 9 (source strength ~160particles/h). During children play, the
      coarse fraction concentration increased by a factor of 3 (source strength
      ~10particles/h). Spraying an insect pesticide increased the coarse fraction
      concentration by a factor of 9 (source strength ~420particles/h). Water-pipe
      tobacco smoking produced huge amounts of both micron and submicron particulate
      matter; it caused the coarse fraction concentration to significantly increase by
      a factor of 18 (source strength ~140particles/h). The use of natural gas heater
      affected the submicron fraction only and did not affect the micron fraction.

PMID- 28437651
TI  - Population attributable risk associated with lung cancer induced by residential
      radon in Canada: Sensitivity to relative risk model and radon probability density
      function choices: In memory of Professor Jan M. Zielinski.
AB  - : Indoor radon has been identified as the second leading cause of lung cancer
      after tobacco smoking. The Population Attributable Risk (PAR) estimates the
      proportion of lung cancer cases associated with indoor radon exposure. Different
      relative risk (RR) models have been used in the literature to calculate PAR. The
      aim of this study is to assess how sensitive PAR is to the relative risk model
      and radon probability distribution functions choices. METHODS: Using Canadian
      observed first floor radon data collected by Health Canada during the period
      October 2010 to March 2011, seven common PAR radon models used for North American
      miners and dwelling scenarios were applied. The death rates used for this study
      were from the period 2006-2009. Smoking data (Ever Smoking ES and Never Smoking
      NS) collected in 2009 was also used in this study. The original discrete radon
      data for Canada overall and for each of its provinces are estimated using log
      normal and Gaussian kernel density estimator distributions. PAR was then
      calculated for Canada and its provinces using the empirical, log-normal, and
      Gaussian kernel estimates distributions. Finally, cancer death cases attributable
      to radon are reported for the constant relative risk model for the three
      distributions and the reduction in the cases when the action level 200Bq/m3 is
      applied. RESULTS: PAR for the Canadian data is sensitive to the model choice, and
      it varies with a range of 10% for ES and 32% for NS, respectively. There is
      little difference in results between miners' models and dwelling models. PAR
      values for ES females are greater than those for ES males, except in
      Saskatchewan, Northwest Territories, Nunavut, and Yukon. The male-female range
      overlaps. Gaussian kernel estimator produces PAR estimates similar to the
      commonly used log-normal distribution. CONCLUSION: Many lung cancer cases could
      be prevented in Canada by reducing indoor radon. PAR is sensitive to the choice
      of RR model. Miners' models can be used for residential radon. Empirical, log
      normal, and Gaussian kernel density estimation with support [0,infinity) can all
      be applied to radon data.

PMID- 28437652
TI  - Review of take-home pesticide exposure pathway in children living in agricultural
      areas.
AB  - BACKGROUND: Children of farmworkers may be chronically exposed to pesticides via
      the take-home exposure pathway. OBJECTIVE: The goal of this review was to analyze
      scientific literature evaluating the role of the take-home pesticide exposure
      pathway in children of agricultural workers. METHODS: A systematic review was
      undertaken and inclusion criteria were applied to identify original articles of
      interest. Of the 30 articles included in this review, some belonged to the same
      studies, resulting in a total of 23 studies. Eight studies assessed environmental
      samples, nine collected biological samples, and the remaining six analyzed both.
      Eleven studies compared pesticide levels between farm and non-farm families.
      RESULTS: There is convincing evidence that children of farmworkers are exposed to
      pesticides at higher levels than "non-agricultural" children, even when residing
      in the same agricultural communities. These levels were shown to depend on the
      season, occupation, number of farmworkers per home, and type of crops. Other
      factors such as age, gender and, sex seem to also influence this pathway. Some
      studies have shown that pesticides used solely in agriculture are found only in
      households of farmworkers spraying these pesticides. Moreover, intervention
      studies have shown that behaviors among farmworkers can significantly lower
      exposure of people living in the same households as farmworkers. DISCUSSION AND
      CONCLUSION: The evidence presented here raises concerns regarding health effects
      associated with exposure to pesticides in children living in agricultural
      communities, and indicates that strategies should be developed to reduce
      exposures in these populations.

PMID- 28437653
TI  - Effects of acidic and neutral biochars on properties and cadmium retention of
      soils.
AB  - In this study, an acidic biochar and a neutral biochar were applied at 5 wt% into
      two soils for an 11-month incubation experiment. One Ferrosol soil (Ba) was
      slightly acidic with low organic matter and the other Dermosol soil (Mt) was
      slightly alkaline with high organic matter. The acidic (pH = 3.25) wood shaving
      (WS) biochar had no marked impact on nutrient levels, cation exchange capacity
      (CEC), pH and acid neutralization capacity (ANC) of either soil. By contrast, the
      neutral (pH = 7.00) chicken litter (CL) biochar significantly increased major
      soluble nutrients, pH, ANC of soil Ba. In terms of C storage, 87.9% and 69.5% WS
      biochar-C can be sequestrated as TOC by soil Ba and Mt, respectively, whereas
      only 24.0% of CL biochar-C stored in soil Ba and negligible amount in Mt as TOC.
      Biochars did not have significant effects on soil sorption capacity and sorption
      reversibility except that CL biochar increased sorption of soil Ba by around
      25.4% and decreased desorption by around 50.0%. Overall, the studied acidic C
      rich WS biochar held little agricultural or remedial values but was favourable
      for C sequestration. The neutral mineral rich CL biochar may provide short-term
      agricultural benefit and certain sorption capacities of lower sorption capacity
      soils, but may be unlikely to result in heightened C sequestration in soils. This
      is the first study comprehensively examining functions of acidic and neutral
      biochars for their benefits as a soil amendment and suggests the importance of
      pre-testing biochars for target purposes prior to their large scale production.

PMID- 28437654
TI  - Enhancement of particle aggregation in the presence of organic matter during
      neutralization of acid drainage in a stream confluence and its effect on arsenic
      immobilization.
AB  - Acid drainage (AD) is an important environmental concern that impacts water
      quality. The formation of reactive Fe and Al oxyhydroxides during the
      neutralization of AD at river confluences is a natural attenuation process.
      Although it is known that organic matter (OM) can affect the aggregation of Fe
      and Al oxyhydroxides and the sorption of As onto their surfaces, the role of OM
      during the neutralization of AD at river confluences has not been studied. Field
      and experimental approaches were used to understand this role, using the Azufre
      River (pH 2) - Caracarani River (pH 8.6) confluence (northern Chile) as model
      system. Field measurements of organic carbon revealed a 10-15% loss of OM
      downstream the confluence, which was attributed to associations with Fe and Al
      oxyhydroxides that settle in the river bed. Laboratory mixtures of AD water with
      synthetic Caracarani waters under varying conditions of pH, concentration and
      type of OM revealed that OM promoted the aggregation of Fe oxyhydroxides without
      reducing As sorption, enhancing the removal of As at slightly acidic conditions
      (pH ~4.5). At acidic conditions (pH ~3), aggregation of OM - metal complexes at
      high OM concentrations could become the main removal mechanism. One type of OM
      promoted bimodal particle size distributions with larger mean sizes, possibly
      increasing the settling velocity of aggregates. This work contributes to a better
      understanding of the role of OM in AD affected basins, showing that the presence
      of OM during processes of neutralization of AD can enhance the removal of toxic
      elements.

PMID- 28437655
TI  - Peripheral artery disease, redox signaling, oxidative stress - Basic and clinical
      aspects.
AB  - Reactive oxygen and nitrogen species (ROS and RNS, e.g. H2O2, nitric oxide)
      confer redox regulation of essential cellular signaling pathways such as cell
      differentiation, proliferation, migration and apoptosis. At higher
      concentrations, ROS and RNS lead to oxidative stress and oxidative damage of
      biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral
      artery disease (PAD) is characterized by severe ischemic conditions in the
      periphery leading to intermittent claudication and critical limb ischemia (end
      stage). It is well known that redox biology and oxidative stress play an
      important role in this setting. We here discuss the major pathways of oxidative
      stress and redox signaling underlying the disease progression with special
      emphasis on the contribution of inflammatory processes. We also highlight
      therapeutic strategies comprising pharmacological (e.g. statins, angiotensin
      converting enzyme inhibitors, phosphodiesterase inhibition) and non
      pharmacological (e.g. exercise) interventions. Both of these strategies induce
      potent indirect antioxidant and anti-inflammatory mechanisms that may contribute
      to an improvement of PAD associated complications and disease progression by
      removing excess formation of ROS and RNS (e.g. by ameliorating primary
      complications such as hyperlipidemia and hypertension) as well as the
      normalization of the inflammatory phenotype suppressing the progression of
      atherosclerosis.

PMID- 28437657
TI  - Toxicity and bioaccumulation of three hexabromocyclododecane diastereoisomers in
      the marine copepod Tigriopus japonicas.
AB  - The three major hexabromocyclododecane (HBCD) diastereoisomers, i.e. alpha-, beta
      and gamma-HBCD, have distinct physical and chemical properties that may
      potentially result in different levels of bioaccumulation and toxicity in aquatic
      organisms. To assess the impact of diastereomeric variation in HBCDs, the marine
      copepod Tigriopus japonicus was exposed to alpha-, beta- and gamma-HBCD in
      isolation. Results showed that all the three diastereoisomers had a similar
      potency to cause growth delay in T. japonicas. Variation was observed in the
      overall survival rate with exposure to alpha- and beta-HBCD, and this resulted in
      significantly higher lethal toxicity in T. japonicas than that with exposure to
      gamma-HBCD. Exposure to alpha-, beta- and gamma-HBCD led to the generation of ROS
      in T. japonicas, a possibly toxic mechanism. Both alpha- and beta-HBCD showed a
      higher potential to induce oxidative stress, which may be a factor in the higher
      lethal toxicity observed with alpha- and beta-HBCD exposure. It is of note that
      T. japonicus was found to be more sensitive to all three diastereoisomers in the
      F1 generation than in the F0 generation. The bioconcentration potential of HBCD
      diastereoisomers can be ranked in the order alpha-HBCD>gamma-HBCD>beta-HBCD and
      was found to be higher in T. japonicus than has been reported for fish species.

PMID- 28437658
TI  - How does first language (L1) influence second language (L2) reading in the brain?
      Evidence from Korean-English and Chinese-English bilinguals.
AB  - To examine how L1 influences L2 reading in the brain, two late bilingual groups,
      Korean-English (KE) and Chinese-English (CE), performed a visual word rhyming
      judgment task in their L2 (English) and were compared to L1 control groups (i.e.,
      KK and CC). The results indicated that the L2 activation is similar to the L1
      activation for both KE and CE language groups. In addition, conjunction analyses
      revealed that the right inferior frontal gyrus and medial frontal gyrus were more
      activated in KK and KE than CC and CE, suggesting that these regions are more
      involved in Korean speakers than Chinese speakers for both L1 and L2. Finally, an
      ROI analysis at the left middle frontal gyrus revealed greater activation for CE
      than for KE and a positive correlation with accuracy in CE, but a negative
      correlation in KE. Taken together, we found evidence that important brain regions
      for L1 are carried over to L2 reading, maybe more so in highly proficient
      bilinguals.

PMID- 28437656
TI  - A gene-environment interaction analysis of plasma selenium with prevalent and
      incident diabetes: The Hortega study.
AB  - BACKGROUND: Selenium and single-nucleotide-polymorphisms in selenoprotein genes
      have been associated to diabetes. However, the interaction of selenium with
      genetic variation in diabetes and oxidative stress-related genes has not been
      evaluated as a potential determinant of diabetes risk. METHODS: We evaluated the
      cross-sectional and prospective associations of plasma selenium concentrations
      with type 2 diabetes, and the interaction of selenium concentrations with genetic
      variation in candidate polymorphisms, in a representative sample of 1452 men and
      women aged 18-85 years from Spain. RESULTS: The geometric mean of plasma selenium
      levels in the study sample was 84.2ug/L. 120 participants had diabetes at
      baseline. Among diabetes-free participants who were not lost during the follow-up
      (N=1234), 75 developed diabetes over time. The multivariable adjusted odds ratios
      (95% confidence interval) for diabetes prevalence comparing the second and third
      to the first tertiles of plasma selenium levels were 1.80 (1.03, 3.14) and 1.97
      (1.14, 3.41), respectively. The corresponding hazard ratios (95% CI) for diabetes
      incidence were 1.76 (0.96, 3.22) and 1.80 (0.98, 3.31), respectively. In
      addition, we observed significant interactions between selenium and polymorphisms
      in PPARGC1A, and in genes encoding mitochondrial proteins, such as BCS1L and
      SDHA, and suggestive interactions of selenium with other genes related to
      selenoproteins and redox metabolism. CONCLUSIONS: Plasma selenium was positively
      associated with prevalent and incident diabetes. While the statistical
      interactions of selenium with polymorphisms involved in regulation of redox and
      insulin signaling pathways provide biological plausibility to the positive
      associations of selenium with diabetes, further research is needed to elucidate
      the causal pathways underlying these associations.

PMID- 28437659
TI  - The relationship between maternal education and the neural substrates of phoneme
      perception in children: Interactions between socioeconomic status and proficiency
      level.
AB  - Relationships between maternal education (ME) and both behavioral performances
      and brain activation during the discrimination of phonemic and nonphonemic sounds
      were examined using fMRI in children with different levels of phoneme
      categorization proficiency (CP). Significant relationships were found between ME
      and intellectual functioning and vocabulary, with a trend for phonological
      awareness. A significant interaction between CP and ME was seen for nonverbal
      reasoning abilities. In addition, fMRI analyses revealed a significant
      interaction between CP and ME for phonemic discrimination in left prefrontal
      cortex. Thus, ME was associated with differential patterns of both
      neuropsychological performance and brain activation contingent on the level of
      CP. These results highlight the importance of examining SES effects at different
      proficiency levels. The pattern of results may suggest the presence of
      neurobiological differences in the children with low CP that affect the nature of
      relationships with ME.

PMID- 28437660
TI  - An experimental analysis of shell failure in breast implants.
AB  - Breast implant durability and the mechanisms of rupture are important topics in
      the medical community, for patients, manufactures and regulatory medical
      agencies. After concerns about the Poly Implant Prosthesis (PIP) implants, the
      need for understanding the adverse outcomes and the failure mode to improve the
      breast implants increased. The objective of this research is to analyze and
      describe the rupture characteristics of failed explanted PIP implants to study
      the modes and causes of rupture. Eleven explanted PIP implants were analyzed by
      visual inspection and scanning electron microscopy (SEM). To simulate
      hypothetical ruptures caused by cyclic mechanical stress (fatigue) in the implant
      shell, two control implants were submitted to fatigue tests, and analyzed with
      SEM. Small ruptures (either Hole or split) striations were found, which normally
      appear due to fatigue phenomena. Similar striations were also found in specimens
      (control) tested under laboratory controlled conditions. In the context of this
      work, the striations found in explants constitute a significant finding as they
      point to the occurrence of fatigue phenomena associated with mammary implants
      rupture. This research, also demonstrates that rupture surface analysis of
      explanted breast implants has the potential to become a useful indicator for
      assessing implant rupture mechanisms.

PMID- 28437661
TI  - Ecological patterns of seed microbiome diversity, transmission, and assembly.
AB  - Seeds are involved in the transmission of microorganisms from one plant
      generation to another and consequently act as the initial inoculum for the plant
      microbiota. The purpose of this mini-review is to provide an overview of current
      knowledge on the diversity, structure and role of the seed microbiota. The
      relative importance of the mode of transmission (vertical vs horizontal) of the
      microbial entities composing the seed microbiota as well as the potential
      connections existing between seed and other plant habitats such as the
      anthosphere and the spermosphere is discussed. Finally the governing processes
      (niche vs neutral) involved in the assembly and the dynamics of the seed
      microbiota are examined.

PMID- 28437662
TI  - Life in earth - the root microbiome to the rescue?
AB  - Manipulation of the soil microbiome holds great promise for contributing to more
      environmentally benign agriculture, with soil microbes such as Pseudomonas
      promoting plant growth and effectively suppressing pathogenic microorganisms.
      Next-generation sequencing has enabled a new generation of research into soil
      microbiomes, presenting the opportunity to better understand and exploit these
      valuable resources. Soil bacterial communities are both highly complex and
      variable, and contain vast interspecies and intraspecies diversity, both of which
      respond to environmental variation. Therefore, we propose that a combination of
      whole microbiome analyses with in-depth examination of key microbial taxa will
      likely prove the most effective approach to understanding rhizosphere microbial
      interactions. This review highlights recent efforts in this direction, based
      around the important biocontrol bacterium Pseudomonas fluorescens.

PMID- 28437663
TI  - Microbial communities associated with plants: learning from nature to apply it in
      agriculture.
AB  - It is a new consensus that any living organism depends on its partners to strive
      under environmental conditions along their living period. Plants are also highly
      dependent on their associated microbes, which can support its development and
      proper protection under stressors. Along their evolution, plants learned to
      interact to soil microbiota, extracting their utmost capacity to provide
      resources for plant development and successful colonization of terrestrial
      systems, where the great soil biodiversity is keen on properly exert this role.
      Functional systems, such as the rhizosphere, provide evidences of the powerful
      selection exerted by plants upon the living soil microbes. In counterpart, the
      anthropogenic activity, mainly in forms of agricultural managements, has
      neglected this symbiosis, interfering in soil biodiversity, and consequently,
      reducing plant development through the interference in their association with
      beneficial microbes. This mini review has collected information to build a
      suitable hypothesis that if we better learn about the connection between plants
      and its associated microbiota in nature, we can lead agriculture to a better
      exploration of this omnipresent source of nutrients and protection, increasing
      yield and sustainability.

PMID- 28437664
TI  - Upscaling of fungal-bacterial interactions: from the lab to the field.
AB  - Fungal-bacterial interactions (FBI) are an integral component of microbial
      community networks in terrestrial ecosystems. During the last decade, the
      attention for FBI has increased tremendously. For a wide variety of FBI,
      information has become available on the mechanisms and functional responses. Yet,
      most studies have focused on pairwise interactions under controlled conditions.
      The question to what extent such studies are relevant to assess the importance of
      FBI for functioning of natural microbial communities in real ecosystems remains
      largely unanswered. Here, the information obtained by studying a type of FBI,
      namely antagonistic interactions between bacteria and plant pathogenic fungi, is
      discussed for different levels of community complexity. Based on this, general
      recommendations are given to integrate pairwise and ecosystem FBI studies. This
      approach could lead to the development of novel strategies to steer terrestrial
      ecosystem functioning.

PMID- 28437665
TI  - Jasmonic acid signalling and the plant holobiont.
AB  - The plant holobiont - which is the plant and its associated microbiome - is
      increasingly viewed as an evolving entity. Some interacting microbes that compose
      the microbiome assist plants in combating pathogens and herbivorous insects.
      However, knowledge of the factors that influence the microbiome in the context of
      defence signalling pathways is still in its infancy. Recent research reported
      that changes in jasmonic acid (JA) and salicylic acid signalling affects the root
      microbiome of Arabidopsis thaliana. This review aims to present the hypothesis
      that the JA pathway represents a novel mechanism for microbiome engineering for
      improved holobiont fitness in agricultural systems.

PMID- 28437666
TI  - Attentional control of emotional interference in children with ADHD and typically
      developing children: An emotional N-back study.
AB  - Emotional interference control refers to the ability to remain focused on goal
      oriented processes when confronted with disrupting but irrelevant emotional
      stimuli, a process that may be impaired in children and adults with attention
      deficit/hyperactivity disorder (ADHD). However, emotional interference levels are
      known to be associated with trait anxiety, and patients with ADHD often display
      elevated levels of trait anxiety, such as these may have confounded previous
      findings of decreased emotional interference control in this population. In the
      present study, male and female 8-13 years old (mean =11.0 years) children with
      ADHD (n=33) and typically developing (TD) children (n=24) performed a visual
      emotional working memory (n-back) task with 2 memory loads and three different
      background pictures (neutral/positive/negative), and trait anxiety measures were
      obtained. Children with ADHD performed less well, and displayed increased
      emotional interference in the presence of aversive distractors when compared with
      TD children. Contrary to our expectations, trait anxiety did not mediate the
      association between diagnostic group membership and the degree of emotional
      interference control; however, co-morbid ODD was associated with decreased levels
      of emotional interference in ADHD. Future research should aim at characterizing
      the mechanisms subtending decreased emotional interference control in the ADHD
      population.

PMID- 28437667
TI  - Social identity shapes stress appraisals in people with a history of depression.
AB  - Ingroup perception or the views people with depression have about their group,
      may influence their vulnerability to social identity threat and lead to enhanced
      stress reactions and impaired performance. It is unclear how ingroup perception
      can influence stress appraisals in performance situations among people with a
      history of depression who are currently in remission. We investigated the impact
      of ingroup perception on primary stress appraisal, i.e. how threatening a test
      situation is perceived, as well as on secondary stress appraisal, or perceived
      coping resources. Sixty people with a history of depression and currently in
      remission underwent computerized performance tests. Ingroup perception (group
      identification, group value and entitativity) and stress appraisals were assessed
      by self-report. In multiple linear regressions higher group identification
      predicted stronger perception of the situation as stressful if participants
      perceived people with depression as a coherent group (high entitativity) and held
      this group in low regard (low group value). In turn, stronger group
      identification was related to more perceived coping resources especially if
      participants did not regard people with depression as a coherent group. Our
      findings highlight the relevance of ingroup perception for stress and coping
      processes in people with a history of depression.

PMID- 28437668
TI  - Genome-wide association study of treatment response to venlafaxine XR in
      generalized anxiety disorder.
AB  - We conducted the first genome-wide association study (GWAS) in Generalized
      Anxiety Disorder (GAD) to identify potential predictors of venlafaxine XR
      treatment outcome. Ninety-eight European American patients participated in a
      venlafaxine XR clinical trial for GAD, with Hamilton Anxiety Scale (HAM-A)
      response/remission at 24 weeks as the primary outcome measure. All participants
      were genotyped with the Illumina PsychChip, and 266,820 common single nucleotide
      polymorphisms (SNPs) were analyzed. Although no SNPs reached genome-wide
      significance, 8 SNPs were marginally associated with treatment response/remission
      and HAM-A reduction at week 12 and 24 (p<0.00001). Several identified genes may
      indicate markers crossing neuropsychiatric diagnostic categories.

PMID- 28437669
TI  - White matter microstructural abnormalities and their association with
      anticipatory anhedonia in depression.
AB  - Anhedonia is associated with dysfunction of the neural circuitry of reward in
      patients with major depressive disorder (MDD). However, its neurobiological basis
      is not fully understood. The present study examined the association between
      anhedonia and white matter (WM) characteristics in patients with first-episode
      MDD. We recruited 30 patients with first-episode drug-naive MDD and 28 healthy
      controls (HC) to undergo diffusion weighted imaging. We examined specifically the
      correlation between WM characteristics and anhedonia measured with the Temporal
      Experience of Pleasure Scale (TEPS) in MDD patients. Using Track-Based Spatial
      Statistics (TBSS), we found that MDD patients exhibited reduced fractional
      anisotropy (FA) in the left cingulum and the forceps minor. These patients also
      exhibited increased radial diffusivity (RD) in several major tracts including the
      bilateral anterior thalamic radiation, the corticospinal tract, the superior
      longitudinal fasciculus and the uncinate fasciculus in the left hemisphere.
      Correlational analysis showed that increased RD was significantly correlated with
      anticipatory anhedonia in the MDD group, while reduced mean FA was correlated
      with consummatory anhedonia in HC. These preliminary findings suggest that left
      sided WM tracts abnormalities may contribute to the development of anhedonia in
      MDD patients.

PMID- 28437670
TI  - A case report of invasive candidiasis and fungal osteomyelitis mimicking
      oropharyngeal carcinoma recurrence in an immunocompetent patient following
      transoral robotic surgery.
AB  - INTRODUCTION: Transoral robotic surgery(TORS) for the excision of oropharyngeal
      tumour is increasingly considered for its lower rates of postoperative
      complications and better functional outcomes. However, we report a case of
      invasive candidiasis in an immunocompetent patient with previous radiation
      therapy years ago who underwent TORS recently. CASE PRESENTATION: A 55year old
      Chinese female with previous radiation therapy for nasopharyngeal carcinoma
      diagnosed in 1986 underwent wide excision of a newly diagnosed oropharyngeal
      carcinoma with TORS. From 4 to 8 weeks post-op, an enlarging exophytic lesion at
      the surgical excision site was noted. Initial biopsy did not show malignancy or
      fungal organisms. A repeat biopsy under anaesthesia was done as CT imaging showed
      suspicion of either infective or tumour recurrence. The patient was treated with
      long term antifungals as final culture results showed invasive candidiasis. The
      surgical site showed no further lesions 6 months post-op. DISCUSSION: Previous
      radiation therapy to the oropharyngeal area predisposes a patient to colonization
      of fungal organisms. Despite TORS showing lower rates of infection, patients who
      have had previous radiotherapy may be more susceptible to infections as the
      dissection involves down to the pre-vertebral fascia. Hence, it is appropriate
      for such patients to have microbiological and fungal cultures performed for a
      lesion such as this and be treated according to the results of the culture.
      CONCLUSION: This case serves as a reminder of the risk of invasive candidiasis
      requiring early investigation and treatment in an immunocompetent patient with
      prior history of both radiation therapy and recent TORS.

PMID- 28437671
TI  - A case report on esophageal tuberculosis - A rare entity.
AB  - This is a case report of a rare form of tuberculosis in a patient presenting with
      dysphagia. Patient was subjected to upper gastrointestinal endoscopy, which
      revealed an ulcerative growth in the distal esophagus. Histopathology revealed
      esophageal tuberculosis. Patient was managed conservatively with Anti
      Tuberculosis Treatment (ATT). Follow up endoscopy after two months revealed
      resolution of the growth and patient was symptomatically better. In spite of the
      rare nature of the disease, it can be managed effectively with ATT to avoid
      complications (fistula, stricture, and esophageal perforation), which might
      warrant surgery.

PMID- 28437672
TI  - Eosinophilic funiculitis initially diagnosed as irreducible inguinal hernia: A
      case report.
AB  - BACKGROUND: Most groin masses are first suspected to be groin hernias. More than
      80% of bulging groin lesions are reportedly diagnosed as hernias by
      ultrasonography. Establishment of the correct diagnosis of hernia among all
      differential diagnoses is not easy. We herein describe a very rare case of groin
      eosinophilic funiculitis that presented as an irreducible groin hernia. CASE
      PRESENTATION: A 59-year-old man presented to our hospital with suspicion of a
      right groin hernia. He had a 1-week history of a painful right groin tumor. The
      tumor was about 4 cm without skin redness or warmth, irreducible even in the
      supine position, and associated with mild tenderness. Enhanced computed
      tomography showed that the mass seemed to be connected to the intra-abdominal
      structures. With time, the patient's pain did not increase, the inflammatory
      response did not worsen, and no ischemic signs were observed by enhanced computed
      tomography. Therefore, we diagnosed the tumor as an irreducible but not
      incarcerated hernia and performed elective surgery. Intraoperative examination
      revealed no hernia sac, and a 4-*3-cm tumor was observed around the spermatic
      cord. A malignant tumor was not completely ruled out. High orchiectomy was
      performed after consultation with the urologists. Pathological examination of the
      tumor showed no malignant features, and the final diagnosis was eosinophilic
      funiculitis with massive inflammatory changes and eosinophil invasion.
      CONCLUSION: Eosinophilic funiculitis is very rare; only three cases have been
      reported to date. We should always consider unusual causes of groin masses during
      a surgical approach to hernia-like lesions.

PMID- 28437673
TI  - Successful primary repair of late diagnosed spontaneous esophageal rupture: A
      case report.
AB  - INTRODUCTION: Spontaneous esophageal rupture is rare, roughly 300 cases reported
      annually. Diagnosis is often delayed or missed. Overall mortality is about 20%.
      This feared high mortality rate has led to the misconception that primary
      esophageal repair should be avoided in late diagnosed patients. We report a
      successful primary repair of spontaneous esophageal rupture which was delayed for
      more than two weeks. METHODS: A 53 year-old male presented to our medical service
      after falsely having been treated for pneumonia at an outside hospital. He was
      subsequently diagnosed with spontaneous esophageal rupture and treated with over
      the scope clips followed by stenting. Persistent leak into mediastinum made
      surgical exploration necessary. At exploration a primary repair could be
      performed successfully. RESULTS: Unsuccessful endoscopic management of esophageal
      perforation that was delayed for two weeks underwent primary surgical repair
      without complications. CONCLUSION: Primary closure of late diagnosed spontaneous
      esophageal rupture can be successful, even when it is complicated by a prolonged
      delay in treatment and failed endoscopic procedures. We conclude that primary
      surgical repair should be attempted in patients with spontaneous esophageal
      rupture if tissues are viable.

PMID- 28437674
TI  - Laparoscopic approach to colo-renal fistula with renal preservation and
      omentoplasty: A case report.
AB  - Colorenal fistula as a result of percutaneous cryoablation has not been
      extensively reported. We report a gentleman who presented with urosepsis after
      percutaneous biopsy of a renal mass complicated by colorenal fistula. After
      failed attempts at conservative management, he underwent laparoscopic resection
      of his fistula with renal salvage and omentoplasty highlighting that nephrectomy
      is not always indicated.

PMID- 28437676
TI  - Superior-inferior position of patellar component affects patellofemoral
      kinematics and contact forces in computer simulation.
AB  - BACKGROUND: Anterior knee pain has been reported as a major postoperative
      complication after total knee arthroplasty, which may lead to patient
      dissatisfaction. Rotational alignment and the medial-lateral position correlate
      with patellar maltracking, which can cause knee pain postoperatively. However,
      the superior-inferior position of the patellar component has not been
      investigated. The purpose of the current study was to investigate the effects of
      the patellar superior-inferior position on patellofemoral kinematics and
      kinetics. METHODS: Superior, central, and inferior models with a dome patellar
      component were constructed. In the superior and inferior models, the position of
      the patellar component translated superiorly and inferiorly, respectively, by
      3mm, relative to the center model. Kinematics of the patellar component,
      quadriceps force, and patellofemoral contact force were calculated using a
      computer simulation during a squatting activity in a weight-bearing deep knee
      bend. FINDINGS: In the inferior model, the flexion angle, relative to the tibial
      component, was the greatest among all models. The inferior model showed an 18.0%,
      36.5%, and 22.7% increase in the maximum quadriceps force, the maximum medial
      patellofemoral force, and the maximum lateral patellofemoral force, respectively,
      compared with the superior model. INTERPRETATION: Superior-inferior positions
      affected patellofemoral kinematic and kinetics. Surgeons should avoid the
      inferior position of the patellar component, because the inferior positioned
      model showed greater quadriceps and patellofemoral force, resulting in a
      potential risk for anterior knee pain and component loosening.

PMID- 28437675
TI  - Whole blood sequencing reveals circulating microRNA associations with high-risk
      traits in non-ST-segment elevation acute coronary syndrome.
AB  - BACKGROUND AND AIMS: Although circulating microRNA (miRNAs) have emerged as
      biomarkers predicting mortality in acute coronary syndrome (ACS), more data are
      needed to understand these mechanisms. Mapping miRNAs to high-risk traits may
      identify miRNAs involved in pathways conferring risk for poor outcome in ACS. We
      aim to investigate the relationship between circulating miRNAs and high-risk
      traits in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS:
      Whole-genome miRNA sequencing was performed on RNA extracted from whole blood of
      199 patients with NSTE-ACS. Generalized linear models were used to test
      associations of miRNAs and 13 high-risk clinical traits, including the Global
      Registry of Acute Coronary Events (GRACE) score, a widely validated risk score
      for mortality in NSTE-ACS. RESULTS: There were 205 nominally significant miRNA
      risk factor associations (p < 0.05) observed. Significant associations occurred
      most frequently with chronic heart failure (HF) (43 miRs), GRACE risk score (30
      miRs), and renal function (32 miRs). In hierarchical cluster analysis, chronic HF
      and GRACE risk score clustered most tightly together, sharing 14 miRNAs with
      matching fold-change direction. Controlling for a false discovery rate of 5%,
      chronic HF was significantly associated with lower circulating levels of miR
      3135b (p < 0.0006), miR-126-5p (p < 0.0001), miR-142-5p (p = 0.0004) and miR-144
      5p (p = 0.0007), while increasing GRACE risk score inversely correlated with
      levels of miR-3135b (p < 0.0001) and positively correlated with levels of miR-28
      3p (p = 0.0002). CONCLUSIONS: Circulating miRs clustered around two powerful
      traits for mortality risk in NSTE-ACS. MiR-3135b, which was under-expressed in
      chronic HF and increasing GRACE risk score, and miR-28-3p, which has no known
      association with cardiovascular disease, warrant further investigation.

PMID- 28437677
TI  - Localization of ENHANCER OF TRY AND CPC1 protein in Arabidopsis root epidermis.
AB  - CAPRICE (CPC) is a R3-type MYB transcription factor, which induces root-hair cell
      differentiation in Arabidopsis thaliana. The CPC homologous gene ENHANCER TRY AND
      CPC1 (ETC1) has a similar function to CPC, and acts in concert with CPC. The CPC
      protein moves between root epidermal cells, from hairless cells to the
      neighboring cells, and promotes root-hair differentiation. Therefore, ETC1 is
      predicted to have movement ability similar to that of CPC. In this study, we
      generated ETC1:ETC1:GFP and CPC:ETC1:GFP transgenic plants to clarify whether
      ETC1 exhibits cell-to-cell movement. Transgenic plants showed many-root-haired
      and trichome-less phenotypes, similar to those observed in CPC:CPC:GFP plants,
      suggesting a similar function of ETC1 and CPC. However, the ETC1:GFP fusion
      protein located exclusively to the hairless cells in both ETC1:ETC1:GFP and
      CPC:ETC1:GFP transgenic plants. These results indicate that, unexpectedly, the
      ETC1 protein cannot move in the root epidermis from hairless cells to the
      neighboring cells.

PMID- 28437679
TI  - Nodal recurrence after stereotactic body radiotherapy for early stage non-small
      cell lung cancer: Incidence and proposed risk factors.
AB  - Stereotactic body radiotherapy (SBRT) is an alternative to surgery for patients
      with early stage non-small cell lung cancer (NSCLC) who are inoperable due to
      comorbid disease or who refuse surgery. SBRT results in an excellent local
      control rate of more than 90%, which is comparable to surgery, while short and
      long-term overall toxicity is low. Surgically treated patients are often more
      extensively staged pre-operatively, e.g. with endobronchial ultrasound and/or
      mediastinoscopy, and typically undergo intra-operative lymph node dissection or
      sampling. Occult nodal metastases (ONM), detected by lymph node dissection, have
      been shown to increase the incidence of regional recurrence (RR) after surgery,
      which is associated with poor outcome. In patients undergoing SBRT, however,
      definite pathological nodal staging is lacking and so other ways to identify
      patients at high risk for ONM and RR are desirable. The aim of this systematic
      review is to summarize the incidence of, and risk factors for, RR after SBRT and
      compare these to those after surgery. The available evidence shows the incidence
      of RR after SBRT or surgery to be comparable, despite more elaborate pre- and
      intra-operative lymph node evaluation in surgical patients. However, the fact
      that this finding is based on mostly retrospective studies in which the majority
      of patients treated with SBRT were inoperable, needs to be taken into
      consideration. For now, there is no evidence that inoperable clinical stage I
      patients with no indication of pathological lymph nodes on PET/CT will benefit
      from more invasive lymph node staging prior to SBRT.

PMID- 28437678
TI  - Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.
AB  - BACKGROUND: New anti-cancer drugs utilize diverse mechanisms of action. Here we
      evaluate their differential efficacy, safety, tolerability and price. METHODS:
      Drugs approved for solid tumor treatment between 2000 and 2015 were identified
      and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics
      (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios
      (HRs) were extracted from the registration trials and pooled in a meta-analysis.
      Odds ratios for toxic death, treatment discontinuation and grade 3-4 toxicity
      were compared to control groups. The Micromedex Red Book was used to calculate
      the monthly price. RESULTS: Analysis included 74 studies comprising 48,527
      patients. Progression-free survival (PFS) was improved to a greater degree with
      groups 1 and 2 than with groups 3 and 4, (pooled HR: 0.54, 0.56, 0.63, and 0.76
      for groups 1-4 respectively, p for difference <0.001). Compared to PFS, there was
      a lower magnitude of improvement overall survival in all groups and the degree of
      benefit was less for group 4 than for other groups (pooled HR: 0.77, 0.78, 0.68,
      and 0.83 for groups 1-4 respectively, p for difference=0.007). Compared to
      control groups in individual trials, immunotherapy was associated with better
      safety and tolerability than other groups. Drug prices have increased over time
      with no significant difference between groups. There was no meaningful
      correlation between pricing and efficacy. CONCLUSIONS: Compared to control
      groups, immunotherapeutics and drugs targeting oncogenes or angiogenesis improve
      efficacy to a greater degree than chemotherapy. Immunotherapy appears to have
      better safety and tolerability profile compared to other cancer therapies. Market
      price of drugs is not related to efficacy.

PMID- 28437680
TI  - How durable is the effect of low intensity CBT for depression and anxiety?
      Remission and relapse in a longitudinal cohort study.
AB  - BACKGROUND: Depression and anxiety disorders are relapse-prone conditions, even
      after successful treatment with pharmacotherapy or psychotherapy. Cognitive
      behavioural therapy (CBT) is known to prevent relapse, but there is little
      evidence of the durability of remission after low intensity forms of CBT (LiCBT).
      METHOD: This study aimed to examine relapse rates 12 months after completing
      routinely-delivered LiCBT. A cohort of 439 LiCBT completers with remission of
      symptoms provided monthly depression (PHQ-9) and anxiety (GAD-7) measures during
      12 months after treatment. Survival analysis was conducted to model time-to
      relapse while controlling for patient characteristics. RESULTS: Overall, 53% of
      cases relapsed within 1 year. Of these relapse events, the majority (79%)
      occurred within the first 6 months post-treatment. Cases reporting residual
      depression symptoms (PHQ-9 = 5 to 9) at the end of treatment had significantly
      higher risk of relapse (hazard ratio = 1.90, p < 0.001). CONCLUSIONS: The high
      rate of relapse after LiCBT highlights the need for relapse prevention,
      particularly for those with residual depression symptoms.

PMID- 28437681
TI  - Predicting wellbeing among people with epilepsy using illness cognitions.
AB  - OBJECTIVE: This study sought to examine the synergistic contribution of illness
      related perceptions (stigma, severity, and threat) and illness behavior to
      wellbeing among people with epilepsy. Poorer wellbeing was expected among those
      who perceived greater stigma, illness severity, and threat and had more extreme
      illness behavior. METHODS: Individuals with a diagnosis of epilepsy (N=210),
      recruited through local and online support groups, completed a questionnaire
      comprising demographic and epilepsy-specific information, and validated measures
      of illness perceptions and behavior, epilepsy-related quality of life, and
      general psychological health. RESULTS: Bivariate associations among illness
      cognition, illness behavior, and wellbeing were all as expected. Structural
      equation modeling highlighted the strong, direct effect of illness threat on
      quality of life, with other contributions from perceived stigma and an abnormal
      illness behavior syndrome (i.e., maladaptive illness responses). Significant
      variance was accounted for in both quality of life (64%) and psychological health
      (34%). CONCLUSION: Preliminary evidence of the contributions of illness threat
      and maladaptive illness responses to wellbeing highlights the need for
      longitudinal research to examine the dynamic nature of such findings. Clinicians
      are encouraged to consider the potential value of screening for both illness
      threat and abnormal illness behavior to facilitate interventions.

PMID- 28437682
TI  - Sleep problems in pediatric epilepsy and ADHD: The impact of comorbidity.
AB  - AIMS: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity
      in pediatric epilepsy. Although sleep problems are commonly reported in both
      children with primary ADHD and epilepsy, those with epilepsy-ADHD comorbidity
      have not been well studied. This study aimed to compare sleep problems among
      three groups of children: 1) children with epilepsy, 2) children with epilepsy
      and ADHD (epilepsy-ADHD), and 3) children with primary ADHD. METHODS: 53 children
      with epilepsy, 35 children with epilepsy-ADHD, and 52 children with primary ADHD
      completed the Children's Sleep Habits Questionnaire (CSHQ). Neurology clinic
      charts were reviewed for the epilepsy-related variables. ADHD subtypes were
      diagnosed according to the DSM-IV. RESULTS: Children with epilepsy-ADHD had the
      highest CSHQ total scores, while children with primary ADHD had higher scores
      than those with epilepsy. Besides the total score, epilepsy-ADHD group differed
      from the primary ADHD and epilepsy groups with higher CSHQ subscores on sleep
      onset delay and sleep anxiety. The frequency of moderate-severe sleep problems
      (CSHQ>56) was 62.9% in children with epilepsy-ADHD, while it was 40.4% and 26.4%
      in children with primary ADHD and epilepsy, respectively. CSHQ total scores were
      not different between ADHD subtypes in both children with epilepsy-ADHD and those
      with primary ADHD. None of the epilepsy-related variables were found to be
      associated with CSHQ scores. DISCUSSION: Epilepsy-ADHD is associated with a
      significantly poor sleep quality which is beyond that of primary ADHD and
      epilepsy.

PMID- 28437683
TI  - PINK1 and Parkin: emerging themes in mitochondrial homeostasis.
AB  - The Parkinson's disease (PD)-associated protein kinase, PTEN-induced putative
      kinase1 (PINK1), and ubiquitin E3 ligase Parkin, function in a common signalling
      pathway known to regulate mitochondrial network homeostasis and quality control,
      including mitophagy. The multistep activation of this pathway, as well as an
      unexpected convergence between the post-translational modifications of
      ubiquitylation and phosphorylation, has added breadth to our understanding of
      cellular damage responses during human disease. In concert with these new
      insights in signal transduction, unique modalities and signatures of vertebrate
      mitophagy have been unravelled in vivo for the very first time. The cell biology
      of mammalian mitophagy, and the roles of PINK1-Parkin signalling in vivo have
      emerged to be more complex than previously thought.

PMID- 28437684
TI  - Fibrillar disruption by AC electric field induced oscillation: A case study with
      human serum albumin.
AB  - The effect of oscillation induced by a frequency-dependent alternating current
      (AC) electric field to dissociate preformed amyloid fibrils has been
      investigated. An electrowetting-on-dielectric type setup has been used to apply
      the AC field of varying frequencies on preformed fibrils of human serum albumin
      (HSA). The disintegration potency has been monitored by a combination of
      spectroscopic and microscopic techniques. The experimental results suggest that
      the frequency of the applied AC field plays a crucial role in the disruption of
      preformed HSA fibrils. The extent of stress generated inside the droplet due to
      the application of the AC field at different frequencies has been monitored as a
      function of the input frequency of the applied AC voltage. This has been
      accomplished by assessing the morphology deformation of the oscillating HSA
      fibril droplets. The shape deformation of the oscillating droplets is
      characterized using image analysis by measuring the dynamic changes in the shape
      dependent parameters such as contact angle and droplet footprint radius and the
      amplitude. It is suggested that the cumulative effects of the stress generated
      inside the HSA fibril droplets due to the shape deformation induced hydrodynamic
      flows and the torque induced by the intrinsic electric dipoles of protein due to
      their continuous periodic realignment in presence of the AC electric field
      results in the destruction of the fibrillar species.

PMID- 28437685
TI  - Rapid label-free identification of Klebsiella pneumoniae antibiotic resistant
      strains by the drop-coating deposition surface-enhanced Raman scattering method.
AB  - Although many methodologies have been developed to identify unknown bacteria,
      bacterial identification in clinical microbiology remains a complex and time
      consuming procedure. To address this problem, we developed a label-free method
      for rapidly identifying clinically relevant multilocus sequencing typing-verified
      quinolone-resistant Klebsiella pneumoniae strains. We also applied the method to
      identify three strains from colony samples, ATCC70063 (control), ST11 and ST15;
      these are the prevalent quinolone-resistant K. pneumoniae strains in East Asia.
      The colonies were identified using a drop-coating deposition surface-enhanced
      Raman scattering (DCD-SERS) procedure coupled with a multivariate statistical
      method. Our workflow exhibited an enhancement factor of 11.3*106 to Raman
      intensities, high reproducibility (relative standard deviation of 7.4%), and a
      sensitive limit of detection (100 pM rhodamine 6G), with a correlation
      coefficient of 0.98. All quinolone-resistant K. pneumoniae strains showed similar
      spectral Raman shifts (high correlations) regardless of bacterial type, as well
      as different Raman vibrational modes compared to Escherichia coli strains. Our
      proposed DCD-SERS procedure coupled with the multivariate statistics-based
      identification method achieved excellent performance in discriminating similar
      microbes from one another and also in subtyping of K. pneumoniae strains.
      Therefore, our label-free DCD-SERS procedure coupled with the computational
      decision supporting method is a potentially useful method for the rapid
      identification of clinically relevant K. pneumoniae strains.

PMID- 28437686
TI  - Synthesis, optical properties and application of a set of novel pyrazole nopinone
      derivatives.
AB  - Pyrazole derivatives (4-6) were directly synthesized from beta-pinene derivative
      nopinone, and they were characterized by Fourier transform infrared (FTIR)
      spectoscope, nuclear magnetic resonance (NMR), and mass spectrometry. Their
      optical properties were investigated by ultraviolet-visible spectroscopy and
      fluorescence spectroscopy. The three compounds emitted strong blue fluorescence
      in ethanol. Using a fluorescence quenching method, compound 4 could be used to
      detect the content (100.57%) of copper sulfate pentahydrate (>=99%) with a RSD of
      1.98%, y=-0.1127*+2.7148, R2=0.9703 (Cu2+: 0.5-8.0*10-5mol/L), and compounds 4-6
      also had utility of calculating the content of anhydrous ferric chloride at a
      wide range of concentration. Thus, compounds 4-6 are new functional fluorescents
      for detecting the content of some purchased products.

PMID- 28437687
TI  - Use of tourmaline as a potential petrogenetic indicator in the determination of
      host magma: CRS, XRD and PED-XRF methods.
AB  - Tourmaline defines a group of complex borosilicate forms as accessory mineral in
      igneous and metamorphic rocks and they act an important role in the
      interpretation of the chemical composition changes of the composition of the host
      fluid of the magma. The variety of tourmaline can be identified by using optical
      microscopy, X-Ray Diffraction (XRD) and by determining its chemical composition
      through Polarized Energy Dispersive X-Ray Fluorescence (PED-XRF) methods.
      However, microscopic investigations and XRD analyses are not quite adequate for
      detailed determination of tourmaline sub-groups. In addition, the use of chemical
      composition of tourmaline as a strict indicator of geochemical processes might be
      a misleading method. In this study, variable tourmaline crystals were collected
      from three different pegmatitic occurrences in Behrekdag, Yozgat and Karakaya
      granitic bodies of Central Anatolia to identify their chemical properties through
      Confocal Raman Spectroscopy (CRS), PED-XRF and XRD analyses. The confocal Raman
      spectrometry of collected tourmalines from the Behrekdag, Yozgat and Karakaya
      granites are in the compositions of schorl, schorl and elbaite respectively. The
      dominant compositional groups of these tourmalines are in the form of schorl.
      Raman shift values of tourmalines revealed four bands centered at almost 1050,
      750, 400 and 300cm-1. The first group of the band arises from SiO stretching, the
      second from BO stretching and the other two belong to bending modes of OBO and
      BOAl with symmetrical deformation of SiOSi. The strongest spectra near 360cm-1
      should belong to the bonding of AlO. As a result, the confocal Raman studies are
      more sensitive for identification of tourmaline subgroup compositions and have a
      quite important in the explaining source of the magma.

PMID- 28437688
TI  - Application of near-infrared spectroscopy for the rapid quality assessment of
      Radix Paeoniae Rubra.
AB  - Near-infrared (NIR) spectroscopy with multivariate analysis was used to quantify
      gallic acid, catechin, albiflorin, and paeoniflorin in Radix Paeoniae Rubra, and
      the feasibility to classify the samples originating from different areas was
      investigated. A new high-performance liquid chromatography method was developed
      and validated to analyze gallic acid, catechin, albiflorin, and paeoniflorin in
      Radix Paeoniae Rubra as the reference. Partial least squares (PLS), principal
      component regression (PCR), and stepwise multivariate linear regression (SMLR)
      were performed to calibrate the regression model. Different data pretreatments
      such as derivatives (1st and 2nd), multiplicative scatter correction, standard
      normal variate, Savitzky-Golay filter, and Norris derivative filter were applied
      to remove the systematic errors. The performance of the model was evaluated
      according to the root mean square of calibration (RMSEC), root mean square error
      of prediction (RMSEP), root mean square error of cross-validation (RMSECV), and
      correlation coefficient (r). The results show that compared to PCR and SMLR, PLS
      had a lower RMSEC, RMSECV, and RMSEP and higher r for all the four analytes. PLS
      coupled with proper pretreatments showed good performance in both the fitting and
      predicting results. Furthermore, the original areas of Radix Paeoniae Rubra
      samples were partly distinguished by principal component analysis. This study
      shows that NIR with PLS is a reliable, inexpensive, and rapid tool for the
      quality assessment of Radix Paeoniae Rubra.

PMID- 28437689
TI  - AIE active turn-off fluorescent probe for the detection of Cu2+ ions.
AB  - A novel AIE active Schiff base compound (receptor 1) has been designed,
      synthesized and characterized spectroscopically. Receptor 1 show weak emission in
      solution state but emit strongly in solid state. The investigation on the AIE
      behavior of receptor 1 using solvent-non-solvent (THF-Water) interaction reveals
      a maximum PL intensity on reaching the water fraction 90% (fw=90) due to
      nanoaggregation. Furthermore, demonstration of metal ion sensing application of
      receptor 1 unravel that it could act as selective and sensitive sensor for Cu2+
      ions in aqueous solution via fluorescence "turn-off" manner. The quenching
      behavior of receptor 1 in presence of Cu2+ ions were evaluated using Stern-Volmer
      plot.

PMID- 28437690
TI  - A guide to nursing students' written reflections for students and educators.
AB  - Experiences from the clinical setting are ideal for building critical thinking
      skills if reflection is used as a teaching tool. Reflective writing is the
      purposeful and recurring inspection of thoughts, feelings, and occurrences that
      coordinate with experiences during practice. Reflecting on clinical experiences
      develops critical thinking ability, fosters self-understanding, facilitates
      coping, and leads to improvement in clinical practice (Kennison, 2006).
      Reflective writing allows students to combine clinical experiences and takeaways
      with didactic material to better understand both practice and instruction.
      Reflective writing is defined as an assignment that is focused on students'
      experiences, like textbook readings, clinical experiences, or group activities,
      that highlights what the student has taken from the activity (McGuire et al.,
      2009). This study will explore reflective writing from the perspective of the
      nursing student and the nurse educator. The following questions will be answered:
      What are the benefits of reflective writing? Why would nurse educators want to
      use reflective writing in their nursing courses, both clinical and didactic? What
      are the barriers to using reflective writing for students and educators? What is
      the role of the nurse educator in student reflection?

PMID- 28437691
TI  - Midwifery participatory curriculum development: Transformation through active
      partnership.
AB  - Evolving knowledge and professional practice combined with advances in pedagogy
      and learning technology create challenges for accredited professional programs.
      Internationally a sparsity of literature exists around curriculum development for
      professional programs responsive to regulatory and societal drivers. This paper
      evaluates a participatory curriculum development framework, adapted from the
      community development sector, to determine its applicability to promote
      engagement and ownership during the development of a Bachelor of Midwifery
      curriculum at an Australian University. The structures, processes and resulting
      curriculum development framework are described. A representative sample of key
      curriculum development team members were interviewed in relation to their
      participation. Qualitative analysis of transcribed interviews occurred through
      inductive, essentialist thematic analysis. Two main themes emerged: (1) 'it is a
      transformative journey' and (2) focused 'partnership in action'. Results
      confirmed the participatory curriculum development process provides symbiotic
      benefits to participants leading to individual and organisational growth and the
      perception of a shared curriculum. A final operational model using a
      participatory curriculum development process to guide the development of
      accredited health programs emerged. The model provides an appropriate structure
      to create meaningful collaboration with multiple stakeholders to produce a
      curriculum that is contemporary, underpinned by evidence and reflective of 'real
      world' practice.

PMID- 28437692
TI  - Stage IV colorectal cancer primary site and patterns of distant metastasis.
AB  - BACKGROUND: Although colorectal cancer (CRC) usually metastasizes to the liver
      and/or lungs, factors influencing the anatomic pattern of metastases remain
      poorly understood. METHODS: We assessed the relationship between primary CRC site
      and pattern of synchronous metastasis among 1202 individuals diagnosed with
      incident metastatic CRC between 2010 and 2014 and identified through the Seattle
      Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry.
      Polytomous logistic regression was used to estimate odds ratios (OR) and 95%
      confidence intervals (CI) for the association between primary tumor site and
      synchronous metastatic pattern. RESULTS: Compared to patients with proximal colon
      primaries, patients with rectal primaries were more likely to present with lungs
      only or liver and lungs metastases versus liver-only metastases (ORlungs
      onlyvs.liver-only: 2.39, 95% CI: 1.35-4.24, ORliver+lungsvs.liver-only: 2.20, 95%
      CI: 1.46-3.32). CONCLUSION: These findings suggest that patients with rectal
      primaries are more likely than patients with colon primaries to present with
      synchronous lung metastases.

PMID- 28437693
TI  - An assessment of the social cognitive predictors of exclusive breastfeeding
      behavior using the Health Action Process Approach.
AB  - RATIONALE: In the United States rates of exclusive breastfeeding duration remain
      exceedingly low. Exclusive breastfeeding is a complex learned behavior that is
      influenced by social cognitive, interpersonal, and structural factors.
      Interventions are needed that address factors at multiple levels of the social
      ecological model. This study was designed to examine the social cognitive
      predictors of exclusive breastfeeding behavior in a sample of low-income women
      attending the Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC) breastfeeding peer counseling program and enrolled in the
      Lactation Advice Through Texting Can Help (LATCH) study. OBJECTIVES: The
      objectives were to examine whether: (1) the theoretical model, the Health Action
      Process Approach (HAPA), fit the data well; (2) planning mediated the effect of
      intentions and maintenance self-efficacy on exclusive breastfeeding; and (3)
      recovery self-efficacy mediated the association between maintenance self-efficacy
      and exclusive breastfeeding behavior. METHODS: Outcome expectancies, action self
      efficacy and intentions were assessed prenatally at baseline in N = 119
      participants. Maintenance self-efficacy, planning, recovery self-efficacy and
      breastfeeding behavior were measured at two weeks post partum. Structural
      equation modeling with mean and variance adjusted Weighted Least Squares
      estimation was used to examine the applicability of the HAPA model to the data.
      RESULTS: Phase specific self-efficacy and planning significantly predicted
      exclusive breastfeeding status. Planning and recovery self-efficacy mediated the
      association between maintenance self-efficacy and exclusive breastfeeding.
      Planning did not emerge as a mediator between intentions and behavior.
      CONCLUSION: These results demonstrate the utility of the HAPA model in predicting
      exclusive breastfeeding behavior among low-income women attending WIC. LATCH is a
      theoretically sound text messaging intervention that can be used to augment and
      reinforce the WIC breastfeeding peer counseling process.

PMID- 28437694
TI  - The benefits of paid maternity leave for mothers' post-partum health and
      wellbeing: Evidence from an Australian evaluation.
AB  - This paper investigates the health effects of the introduction of a near
      universal paid parental leave (PPL) scheme in Australia, representing a natural
      social policy experiment. Along with gender equity and workforce engagement, a
      goal of the scheme (18 weeks leave at the minimum wage rate) was to enhance the
      health and wellbeing of mothers and babies. Although there is evidence that
      leave, especially paid leave, can benefit mothers' health post-partum, the
      potential health benefits of implementing a nationwide scheme have rarely been
      investigated. The data come from two cross-sectional surveys of mothers (matched
      on their eligibility for paid parental leave), 2347 mother's surveyed pre-PPL and
      3268 post-PPL. We investigated the scheme's health benefits for mothers, and the
      extent this varied by pre-birth employment conditions and job characteristics.
      Overall, we observed better mental and physical health among mothers after the
      introduction of PPL, although the effects were small. Post-PPL mothers on casual
      (insecure) contracts before birth had significantly better mental health than
      their pre-PPL counterparts, suggesting that the scheme delivered health benefits
      to mothers who were relatively disadvantaged. However, mothers on permanent
      contracts and in managerial or professional occupations also had significantly
      better mental and physical health in the post-PPL group. These mothers were more
      likely to combine the Government sponsored leave with additional, paid, employer
      benefits, enabling a longer paid leave package post-partum. Overall, the study
      provides evidence that introducing paid maternity leave universally delivers
      health benefits to mothers. However the modest 18 week PPL provision did little
      to redress health inequalities.

PMID- 28437695
TI  - Fe(III)-promoted transformation of beta-lactam antibiotics: Hydrolysis vs
      oxidation.
AB  - The widely used beta-lactam antibiotics are susceptible to oxidative and/or
      hydrolytic degradation promoted by some metal ions (e.g., Cu(II)). Ferric ions
      (Fe(III)) are among the most common metal ions, but their role in the
      environmental transformation and fate of beta-lactam antibiotics is still
      unknown. This study elucidates that Fe(III) can promote degradation of beta
      lactam antibiotics under environmental aquatic conditions. Degradation rate
      constants of ampicillin (AMP) linearly increased with increasing Fe(III)
      concentration, but were independent of AMP concentration when AMP was higher than
      Fe(III) concentration. Neutral pH was most favorable for Fe(III)-promoted
      degradation of AMP, and the promoted degradation was also significant in real
      surface water and wastewater matrix. Among the various beta-lactam antibiotics,
      Fe(III)-promoted degradation of penicillins was faster than that of
      cephalosporins. Product analysis indicated that only two isomers of hydrolysis
      products were observed without detection of oxidation products. The Fe(III)
      promoted degradation likely occurred via complexation of beta-lactam antibiotics
      with carboxyl group and tertiary nitrogen, and then enhancing the hydrolytic
      cleavage of beta-lactam ring. This study is among the first to identify the role
      of Fe(III) in the degradation of beta-lactam antibiotics and elucidate the
      mechanism. The new findings indicate iron species are among the factors affecting
      the environmental fate of beta-lactam antibiotics.

PMID- 28437697
TI  - Catalytic polymer-clay composite for enhanced removal and degradation of
      diazinon.
AB  - It is well established that organophosphate pesticides, such as diazinon, pose
      environmental and health risks. Diazinon is prone to rapid acidic hydrolysis,
      forming the less toxic compound 2-isopropyl-6-methyl-4-pyrimidinol (IMP). In this
      study, diazinon surface catalyzed hydrolysis was achieved by its adsorption to a
      composite, based on protonated poly (4-vinyl-pyridine-co-styrene) (HPVPcoS) and
      montmorillonite (MMT) clay. The adsorption affinity and kinetics of diazinon to
      HPVPcoS-MMT were significantly higher than those obtained to the deprotonated
      PVPcoS-MMT, emphasizing the importance of hydrogen bonding. Correspondingly,
      diazinon filtration by HPVPcoS-MMT columns was highly efficient (100% for 100
      pore volumes), while filtration by columns of PVPcoS-MMT or granular activated
      carbon (GAC) reached only 55% and 85%, respectively. Regeneration of HPVPcoS-MMT
      by pH increase was demonstrated and sorbent reuse was successful, whereas
      regeneration and reuse of GAC and PVPcoS-MMT were inefficient. Proton transfer
      from HPVPcos-MMT to diazinon, investigated by FTIR analysis, supports the
      suggested mechanism of surface catalyzed hydrolysis. These findings demonstrate
      the applicability of such bi-functional sorbents, to adsorb and degrade
      pollutants, for efficient water treatment.

PMID- 28437696
TI  - Different toxicity of anatase and rutile TiO2 nanoparticles on macrophages:
      Involvement of difference in affinity to proteins and phospholipids.
AB  - TiO2 nanoparticles (NPs) are well-known nanomaterials (NMs), widely used in
      cosmetics, solar cells, photo-catalysts and additives. Anatase and rutile are the
      two main crystalline phases of TiO2 NPs and have distinct electrical and optical
      properties. However, their relative toxicity to organisms is a current topic of
      debate. In this study, we synthesize both anatase NPs (TiO2-A) and rutile NPs
      (TiO2-R) with similar particle sizes (20-40nm), surface areas (51-52m2/g) and
      Zeta potentials (-13.4 to -13.7mV), and investigate their toxicity to
      macrophages. Contrary to previous findings, TiO2-A show a lower percentage cell
      deaths compared to TiO2-R (10% vs 20% at 50mg/L), indicating a lower toxicity
      compared to TiO2-R. The macrophages treated with TiO2-A and TiO2-R have similar
      levels of reactive oxygen species (ROS) and the autophagy marker LC3, implying
      that our observed difference in toxicity is not attributed to oxidative damage
      and autophagy. Interestingly, TiO2-A cause less severe necrosis and lysosomal
      membrane permeabilization (LMP), but more severe mitochondrial dysfunction.
      Adsorption assays further reveal that TiO2-A and TiO2-R have a higher affinity to
      proteins and phospholipids, respectively. This study demonstrates an important
      role of crystal phase-related surface affinity to different biomolecules in
      nanotoxicity.

PMID- 28437698
TI  - Coupled elasticity in soft solid foams.
AB  - Elasticity of soft materials can be greatly influenced by the presence of air
      bubbles. Such a capillary effect is expected for a wide range of materials, from
      polymer gels to concentrated emulsions and colloidal suspensions. Whereas
      experimental results and theory exist for describing the elasto-capillary
      behavior of bubbly materials (i.e. with moderate gas volume fractions), foamy
      systems still require a dedicated study in order to increase our understanding of
      elasticity in aerated materials over the full range of gas volume fractions. Here
      we elaborate well-controlled foams with concentrated emulsion and we measure
      their shear elastic modulus as a function of gas fraction, bubble size and
      elastic modulus of the emulsion. Such complex foams possess the elastic features
      of both the bubble assembly and the interstitial matrix. Moreover, their elastic
      modulus is shown to be governed by two parameters, namely the gas volume fraction
      and the elasto-capillary number, defined as the ratio of the emulsion modulus
      with the bubble capillary pressure. We connect our results for foams with
      existing data for bubbly systems and we provide a general view for the effect of
      gas bubbles in soft elastic media. Finally, we suggest that our results could be
      useful for estimating the shear modulus of aqueous foams and emulsions with
      multimodal size distributions.

PMID- 28437699
TI  - Structure and dynamics of cetyltrimethylammonium chloride-sodium dodecylsulfate
      (CTAC-SDS) catanionic vesicles: High-value nano-vehicles from low-cost
      surfactants.
AB  - HYPOTHESIS: Catanionic vesicles based on large-scale produced surfactants
      represent a promising platform for the design of innovative, effective and
      relatively inexpensive nano-vehicles for a variety of actives. Structural,
      dynamic and functional behavior of these aggregates is finely tuned by the
      molecular features of their components and can be opportunely tailored for their
      applications as drug carriers. EXPERIMENTS: Here we investigate the aggregates
      formed by CTAC and SDS, two of the most diffused surfactants, by means of Dynamic
      Light Scattering, Small Angle Neutron Scattering and Electron Paramagnetic
      Resonance spectroscopy (EPR). The exploitation of these aggregates as nano
      vehicles is explored using the poorly water-soluble antioxidant trans-resveratrol
      (t-RESV), testing t-RESV solubility and antioxidant activity by means of UV,
      fluorescence spectroscopy and EPR. FINDINGS: The presence of a large stability
      region of catanionic vesicles on the CTAC-rich side of the phase diagram is
      highlighted and interpreted in terms of the mismatch between the lengths of the
      surfactant tails and of first reported effects of the chloride counterions. CTAC
      SDS vesicles massively solubilize t-RESV, which in catanionic vesicles exerts a
      potent antioxidant and radical-scavenging activity. This behavior arises from the
      positioning of the active at the surface of the vesicular aggregates thus being
      sufficiently exposed to the external medium.

PMID- 28437700
TI  - Nanomolar electrochemical detection of caffeic acid in fortified wine samples
      based on gold/palladium nanoparticles decorated graphene flakes.
AB  - Amalgamation of noble metal nanomaterials on graphene flakes potentially paves
      one way to improve their physicochemical properties. This paper deals with the
      simultaneous electrochemical deposition of gold and palladium nanoparticles on
      graphene flakes (Au/PdNPs-GRF) for the sensitive determination of caffeic acid
      (CA). The physiochemical properties of the prepared Au/PdNPs-GRF was
      characterized by using numerous analytical techniques such as scanning electron
      microscopy, electron dispersive X-ray spectroscopy, Fourier transform infrared
      spectroscopy, X-ray powder diffraction, Raman spectroscopy and electrochemical
      impedance spectroscopy. The enhanced electrochemical determination of CA at
      Au/PdNPs deposition on GRF were studied by using cyclic voltammetry and
      differential pulse voltammetry. In results, Au/PdNPs-GRF electrode exhibited an
      excellent electrocatalytic activity towards CA with wide linear range and low
      limit of detection of 0.03-938.97uM and 6nM, respectively. Eventually, the
      Au/PdNPs-GRF was found as a selective and stable active material for the sensing
      of CA. In addition, the proposed sensor showed the adequate results in real
      sample analysis.

PMID- 28437701
TI  - A high performance and highly-controllable core-shell imprinted sensor based on
      the surface-enhanced Raman scattering for detection of R6G in water.
AB  - A novel, sensitive sensor material combined the technique of surface enhance
      Raman scattering (SERS) and molecular imprinting was prepared. It was used the
      amino-functionalized SiO2 nanospheres as the supporting materials and anchored Ag
      nanoparticles on the surface by the function of coordination between Ag+ and NH2
      . Then, it was used that the Rhodamine 6G (R6G) as the template, acrylamide (AM)
      as functional monomer, ethyleneglycol dimethacrylate (EGDMA) as cross-linker,
      2,2'-azobis(2-methylpropionitrile) (AIBN) as initiator to prepare the core-shell
      molecular imprinted polymers. Prominently, the shell thickness could be
      controlled by the regulation of cross-linker dosage and it was found that the
      SERS detection signal was most obvious when the shell thickness was about 40nm.
      Under the optimal condition, it was presented good linear relationship (R2=0.93)
      between the Raman signal (at 1505cm-1) and the concentration of the templates and
      the limit of detection was 10-12molL-1. Meanwhile, the selective experiment was
      proved that this materials owned specific selectivity to the template. It was
      confirmed that the core-shell molecular imprinted polymers were a kind of highly
      sensitive and selective sensor materials in the field of R6G detection.

PMID- 28437702
TI  - Cascade post-polymerization modification of single pentafluorophenyl ester
      bearing homopolymer as a facile route to redox-responsive nanogels.
AB  - Poly(pentafluorophenyl methacrylate) (PPFPMA) was first subjected to post
      polymerization modification with oligo(ethylene glycol) methyl ether amine (OEG
      NH2) and yielded poly(pentafluorophenyl methacrylate)-co-poly(oligo(ethylene
      glycol methacrylamide)), PPFPMA-co-POEGMAM. These amphiphilic random copolymers
      can self-assemble into micellar nanoparticles in water having sizes less than
      100nm. By tandemly reacting the pentafluorophenyl (PFP) groups in the copolymeric
      nanoparticles with a dithiol crosslinker, cystamine, redox-responsive nanogels
      can be formed. The last step of post functionalization with isopropylamine was
      introduced in order to remove the remaining PFP groups in the nanogels. Stepwise
      post functionalization can be monitored by FTIR and 19F NMR spectroscopy. Release
      of a model hydrophobic drug, nile red (NR) from the nanogels, simultaneously
      encapsulated during micelles formation, can be accelerated in the presence of
      glutathione (GSH) especially at 37 degrees C. Results from cytocompatibility
      evaluation suggested that these developed redox-responsive nanogels strongly
      possessed a potential for applications in controlled delivery.

PMID- 28437703
TI  - Antiviral treatment strategies based on gene silencing and genome editing.
AB  - The ability of some viruses to establish latently infected chronic reservoirs
      that escape to immune control becomes a major roadblock that impedes the cure of
      these infections. Therefore, new alternatives are needed to pursuit the
      eradication of viral persistent infections. Gene silencing technologies are in
      constant evolution and provide an outstanding sequence specificity that allows
      targeting any coding sequence of interest. Here we provide an overview of the
      development of gene silencing technologies ranging from initially RNA
      interference to the recently developed CRISPR/Cas9 and their potential as new
      antiviral strategies focusing on the eradication of HIV.

PMID- 28437704
TI  - Conserved RNA polymerase II initiation complex structure.
AB  - Recent cryo-electron microscopic studies have arrived at atomic models of the
      core transcription initiation complex comprising RNA polymerase (Pol) II and the
      basal transcription factors TBP, TFIIA, TFIIB, TFIIE, and TFIIF. A detailed
      comparison of two independently derived yeast and human core initiation complex
      structures reveals that they are virtually identical, demonstrating the
      conservation of the basic transcription machinery amongst eukaryotes. The
      additional factors TFIID, TFIIH, and Mediator have been located on the periphery
      of the core initiation complex, providing the topology of the entire initiation
      assembly, which comprises approximately 70 polypeptides with a molecular weight
      of ~4 Megadalton.

PMID- 28437705
TI  - Both heavy metal-amendment of soil and aphid-infestation increase Cd and Zn
      concentrations in phloem exudates of a metal-hyperaccumulating plant.
AB  - Plants that are able to hyperaccumulate heavy metals show increased
      concentrations of these metals in their leaf tissue. However, little is known
      about the concentrations of heavy metals and of organic defence metabolites in
      the phloem sap of these plants in response to either heavy metal-amendment of the
      soil or biotic challenges such as aphid-infestation. In this study, we
      investigated the effects of heavy metal-exposure and of aphid-infestation on
      phloem exudate composition of the metal hyperaccumulator species Arabidopsis
      halleri L. O'Kane & Al-Shehbaz (Brassicaceae). The concentrations of elements and
      of organic defence compounds, namely glucosinolates, were measured in phloem
      exudates of young and old (mature) leaves of plants challenged either by
      amendment of the soil with cadmium and zinc and/or by an infestation with the
      generalist aphid Myzus persicae. Metal-amendment of the soil led to increased
      concentrations of Cd and Zn, but also of two other elements and one indole
      glucosinolate, in phloem exudates. This enhanced defence in the phloem sap of
      heavy metal-hyperaccumulating plants can thus potentially act as effective
      protection against aphids, as predicted by the elemental defence hypothesis.
      Aphid-infestation also caused enhanced Cd and Zn concentrations in phloem
      exudates. This result provides first evidence that metal-hyperaccumulating plants
      can increase heavy metal concentrations tissue-specifically in response to an
      attack by phloem-sucking herbivores. Overall, the concentrations of most
      elements, including the heavy metals, and glucosinolates were higher in phloem
      exudates of young leaves than in those of old leaves. This defence distribution
      highlights that the optimal defence theory, which predicts more valuable tissue
      to be better defended, is applicable for both inorganic and organic defences.

PMID- 28437706
TI  - Three phases in pH dependent heme abstraction from myoglobin.
AB  - The extent of heme extraction from myoglobin (Mb) by methylethyl ketone is found
      to be pH dependent and show three distinct phases. Parallel investigations of the
      protein using resonance Raman (rR) and circular dichroism (CD) across these pH
      regions indicate that these phases correspond to three different protonation
      steps in holoMb as the pH of the solution changed. The first transition occurs
      between pH5-6 and is due to the protonation of one of the heme propionate groups
      which disrupts its H-bonding with Arg 45 in the loop. The 2nd phase (pH5-4)
      likely involves the protonation of the 2nd propionate which H-bonds to Ser 92 in
      the F-helix. The third phase (pH<3.5) involves dissociation of the FeIIHis bond
      which eventually leads to complete heme dissociation and unfolding.

PMID- 28437707
TI  - Effect of pCO2 on direct flue gas mineral carbonation at pilot scale.
AB  - Concerns about global warming phenomena induced the development of research about
      the control of anthropogenic greenhouse gases emissions. The current work studies
      on the scaling up of aqueous mineral carbonation route to reduce the CO2
      emissions at the chimney of industrial emitters. The reactivity of serpentinite
      in a stirred tank reactor was studied for several partial pressures of CO2 (pCO2)
      (0.4, 0.7, 1.3 and 1.6 bar). Prior to carbonation, the feedstock was finely
      grinded and dehydroxyled at 650  degrees C by a thermal treatment. The major
      content of magnetite was removed (7.5 wt% . total weight-1). Experiments were
      carried out under batch mode at room temperature using real cement plant flue gas
      (14-18 vol% CO2) and open pit drainage water. The effect of the raw water and the
      pCO2 on the carbonation efficiency was measured. First, the main results showed a
      positive effect of the quarry water as a slight enhancement of the Mg leaching in
      comparison with distilled water. Secondly, a pCO2 of 1.3 bar was the optimal
      working pressure which provided the highest efficiency of the carbonation
      reaction (0.8 gCO2 . g residue-1). Precipitation rates of dissolved CO2 ranged
      from 7% to 33%. Pure precipitate was obtained and essentially composed of
      Nesquehonite. At a pCO2 of 1.3 bar, additional physical retreatment of the solid
      material after being contacted with 6 batches of gas enhanced considerably
      mineral carbonation efficiency (0.17 gCO2 . g residue-1.).

PMID- 28437709
TI  - Long-term outcome of GIST patients treated with delayed imatinib therapy.

PMID- 28437708
TI  - Primary, secondary and tertiary prevention of human papillomavirus-driven head
      and neck cancers.
AB  - Human papillomavirus (HPV)-driven oropharyngeal cancers (OPCs) represent an
      increasing proportion of head and neck cancers that could become, in the next few
      decades, a public health problem in certain western countries. This significant
      epidemiological change strongly calls for preventive measures. Prophylactic HPV
      vaccination and screening programmes for early identification and treatment of
      premalignant lesions are currently being used to reduce the incidence of uterine
      cervical cancer, which is the paradigm of HPV-driven malignancy. These strategies
      have proven to be efficient as the incidence of cervical cancer has dramatically
      dropped since the 1960s in most countries where they are properly applied. The
      success of cervical cancer prevention encourages the development of similar
      approaches to prevent HPV-driven OPCs. However, a number of important limitations
      impede their application to HPV-driven OPCs, and the development of innovative
      and specific strategies dedicated to this disease are urgently needed. This
      article provides an overview on primary, secondary and tertiary prevention of HPV
      driven OPC and discusses some directions for future research.

PMID- 28437710
TI  - Customised nucleic acid libraries for enhanced aptamer selection and performance.
AB  - Aptamers are short single-stranded oligo(deoxy)nucleotides that are selected to
      bind to target molecules with high affinity and specificity. Because of their
      sophisticated characteristics and versatile applicability, aptamers are thought
      to become universal molecular probes in biotechnological and therapeutic
      applications. However, the variety of possible interactions with a putative
      target molecule is limited by the chemical repertoire of the natural nucleobases.
      Consequently, many desired targets are not addressable by aptamers. This obstacle
      is overcome by broadening the chemical diversity of aptamers, mainly achieved by
      nucleobase-modifications and the introduction of novel bases or base pairs. We
      discuss these achievements and the characteristics of the respective modified
      aptamers, reflected by SOMAmers (slow off-rate modified aptamers), clickmers, and
      aptamers bearing an expanded genetic alphabet.

PMID- 28437711
TI  - Cardiomyocyte Ca2+ homeostasis as a therapeutic target in heart failure with
      reduced and preserved ejection fraction.
AB  - Heart failure is a highly prevalent syndrome of multiple etiologies and
      associated comorbidities, and aberrant intracellular Ca2+ homeostasis is a
      hallmark finding in heart failure patients. The cyclical changes in Ca2+
      concentration within cardiomyocytes control cycles of cardiac contraction and
      relaxation, and dysregulation of Ca2+ handling processes leads to systolic
      dysfunction, diastolic dysfunction, and adverse remodeling. For this reason,
      greater understanding of Ca2+ handling mechanisms in heart failure is critical
      for selection of appropriate treatment strategies. In this review, we summarize
      the mechanisms of altered Ca2+ handling in two subsets of heart failure, heart
      failure with reduced ejection fraction and heart failure with preserved ejection
      fraction, and outline current and experimental treatments that target
      cardiomyocyte Ca2+ handling processes.

PMID- 28437712
TI  - Raspberry pomace alters cecal microbial activity and reduces secondary bile acids
      in rats fed a high-fat diet.
AB  - The profile of bile acids (BA) largely depends on the enzymatic activity of the
      microbiota, but this can be modulated by the dietary addition of biologically
      active compounds, e.g., polyphenols and polyunsaturated fatty acids. The aim of
      this study was to examine the effect of dietary raspberry pomace as a rich source
      of biologically active compounds on microbial activity and the BA profile in the
      caecum of rats fed a high-fat diet. Wistar rats were fed the standard diet AIN
      93, a high-fat diet or a modified high-fat diet enriched with 7% different types
      of processed raspberry pomaces produced by standard grinding and fine grinding,
      with or without seeds. Rats fed the high-fat diet for 8 weeks showed some
      disorders in liver function and cecal BA, as manifested by an increased
      concentration of cholesterol, total BA in the liver and cholic, deoxycholic, and
      beta-muricholic acids in the cecal digesta. In general, irrespective of the type
      of raspberry pomace, these dietary preparations decreased liver cholesterol,
      hepatic fibroblast growth factor receptor 4, peroxisome proliferator-activated
      receptor alpha, cecal ammonia and favorable changed BA profile in the cecum.
      However, among all dietary pomaces, the finely ground preparation containing
      seeds had the greatest beneficial effect on the caecum by modulating bacterial
      activity and reducing the levels of secondary BA.

PMID- 28437713
TI  - Reference intervals for serum 24,25-dihydroxyvitamin D and the ratio with 25
      hydroxyvitamin D established using a newly developed LC-MS/MS method.
AB  - 24,25(OH)2D is the product of 25(OH)D catabolism by CYP24A1. The measurement of
      serum 24,25(OH)2D concentration may serve as an indicator of vitamin D catabolic
      status and the relative ratio with 25(OH)D can be used to identify patients with
      inactivating mutations in CYP24A1. We describe a LC-MS/MS method to determine:
      (1) the relationships between serum 24,25(OH)2D and 25(OH)D; (2) serum reference
      intervals in healthy individuals; (3) the diagnostic accuracy of 24,25(OH)2D
      measurement as an indicator for vitamin D status; 4) 24,25(OH)2D cut-off value
      for clinically significant change between inadequate and sufficient 25(OH)D
      status. Serum samples of healthy participants (n=1996) from Army recruits and
      patients (n=294) were analysed. The LC-MS/MS assay satisfied industry standards
      for method validation. We found a positive, concentration-dependent relationship
      between serum 24,25(OH)2D and 25(OH)2D concentrations. The 25(OH)D:24,25(OH)2D
      ratio was significantly higher (P<.001) at 25(OH)D<50 nmol/L. The reference
      interval for 25(OH)D:24,25(OH)2D ratio in healthy subjects was 7-23. Measurement
      of serum 24,25(OH)2D can be used as predictor of vitamin D status, a
      concentration of>4.2 nmol/L was identified as a diagnostic cut-off for 25(OH)D
      replete status. One patient sample with an elevated 25(OH)D:24,25(OH)2D ratio of
      32 and hypercalcaemia who on genetic testing confirmed to have a biallelic
      mutation of CYP24A1. Our study demonstrated the feasibility of a combined
      24,25(OH)2D and 25(OH)D assessment profile. Our established cut-off value for
      24,25(OH)2D and ratio reference ranges can be useful to clinicians in the
      investigation of patients with an impaired calcium/phosphate metabolism and may
      point towards the existence of CYP24A1 gene abnormalities.

PMID- 28437715
TI  - Parameterization of NMR relaxation curves in terms of logarithmic moments of the
      relaxation time distribution.
AB  - This work addresses the problem of a compact and easily comparable representation
      of multi-exponential relaxation data. It is often convenient to describe such
      data in a few parameters, all being of physical significance and easy to
      interpret, and in such a way that enables a model-free comparison between
      different groups of samples. Logarithmic moments (LMs) of the relaxation time
      constitute a set of parameters which are related to the characteristic relaxation
      time on the log-scale, the width and the asymmetry of an underlying distribution
      of exponentials. On the other hand, the calculation of LMs does not require
      knowing the actual distribution function and is reduced to a numerical
      integration of original data. The performance of this method has been tested on
      both synthetic and experimental NMR relaxation data which differ in a signal-to
      noise ratio, the sampling range and the sampling rate. The calculation of two
      lower-order LMs, the log-mean time and the log-variance, has proved robust
      against deficiencies of the experiment such as scattered data point and
      incomplete sampling. One may consider using them as such to monitor formation of
      a heterogeneous structure, e.g., in phase separation, vitrification,
      polymerization, hydration, aging, contrast agent propagation processes. It may
      also assist in interpreting frequency and temperature dependences of relaxation,
      revealing a crossover from slow to fast exchange between populations. The third
      LM was found to be a less reliable quantity due to its susceptibility to the
      noise and must be used with caution.

PMID- 28437714
TI  - Additional value of venous phase added to aortic CT angiography in patients with
      aortic aneurysm.
AB  - PURPOSE: To compare diagnostic performance of unenhanced and CTA images (Image
      set 1) to that of combined unenhanced, CTA, and venous-phase images (Image set 2)
      for incidentalomas in patients with aortic aneurysm. METHODS: Preoperative CT
      Images of consecutive 240 patients were reviewed by two observers for
      incidentalomas. Diagnostic performance was assessed. RESULTS: Sensitivity was
      higher in Image set 2 than Image set 1 in observer 1 and overall (P=0.03 and
      0.00). AUCs for both observers were higher in Image set 2 than Image set 1
      (P=0.03 and 0.01). CONCLUSION: Addition of venous-phase to CTA significantly
      improved diagnostic performance of incidentalomas.

PMID- 28437716
TI  - Development of a derivatization method for the quantification of hydrogen sulfide
      and its application in vascular calcification rats.
AB  - Hydrogen sulfide (H2S) plays major functional and structural roles in diverse
      physiological functions and the pathogenesis of a variety of disorders in
      biological matrices. The significance of H2S has prompted the development of
      sensitive and selective methods to determine its concentration in biological
      samples. The fluorescent reagent monobromobimane (MBB) has been widely used to
      measure various thiol-containing species through alkylation. MBB may prevent the
      oxidation of sulfide and the reaction of sulfide with several different species
      (such as superoxide radicals, hydrogen peroxide and peroxynitrite). An isomers of
      MBB, 3-(bromomethyl)-2, 6, 7-trimethyl-1H, 5H-pyrazolo [1,2-a] pyrazole-1, 5
      dione (MMB), is cheaper than MBB and its use in the analysis of H2S has not
      previously been reported. In the present study, we compared the derivatization
      reactions of hydrogen sulfide with MMB and MBB and developed a sensitive method
      to quantify H2S in blood. In our method, H2S was incubated in the dark with
      excess MMB in 0.1M Tris-HCl buffer (pH 10.1) at 50 degrees C for 120min. 50MUL
      aliquots of the derivatized product were analyzed using HPLC system with gradient
      elution of 0.1% (v/v) formic acid-acetonitrile. The limit of detection for the
      derivatized product was 0.03nmol/mL. The derivatization reaction was suitable for
      detecting low concentrations of H2S. The derivate product is stable over time,
      permitting batch storage and analysis.

PMID- 28437717
TI  - Traumatic axonal injury, a clinical-pathological correlation.
AB  - Traumatic axonal injury (TAI) is a distinct clinicopathological entity that can
      cause serious impairment of the brain function and can sometimes be found as a
      concrete cause of death. It has been discussed from the perspective of its
      biomechanical importance, and also from the standpoint of certain criteria for
      the pathological diagnosis of TAI. However, since the time when DAI (diffuse
      axonal injury) was initially described, there have been few, if any, discussions
      about the clinical-pathological correlation in TAI. This paper is an attempt to
      address this issue. For the purpose of certain pathological diagnoses of TAI, 63
      cases with closed head injuries have been subjected to the complete forensic
      neuropathological examination, involving immunohistochemistry with antibody
      against beta-APP. In the diagnosis of TAI strict criteria have been followed.
      Then, retrograde analysis of the clinical parameters has been performed in order
      to determine some clinical-pathological correlation. The following two most
      reliable parameters of the impairment of the brain function have been analyzed:
      the impairment of the consciousness and the time of survival. Comparing the two
      groups, the one with TAI and the other without TAI, and using appropriate
      statistical evaluation, our results show that TAI is not a significant
      contributing factor to the lethal outcome in the early post injury period (24 h),
      but it is undoubtedly a contributing factor for the severe impairment of the
      brain function indicated through the status of the consciousness.

PMID- 28437718
TI  - Nontargeted metabolomics approach for the differentiation of cultivation ages of
      mountain cultivated ginseng leaves using UHPLC/QTOF-MS.
AB  - The adulteration or falsification of the cultivation age of mountain cultivated
      ginseng (MCG) has been a serious problem in the commercial MCG market. To develop
      an efficient discrimination tool for the cultivation age and to explore potential
      age-dependent markers, an optimized ultra high-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS)-based
      metabolomics approach was applied in the global metabolite profiling of 156 MCG
      leaf (MGL) samples aged from 6 to 18 years. Multivariate statistical methods such
      as principal component analysis (PCA) and partial least squares discriminant
      analysis (PLS-DA) were used to compare the derived patterns between MGL samples
      of different cultivation ages. The present study demonstrated that 6-18-year-old
      MGL samples can be successfully discriminated using two simple successive steps,
      together with four PLS-DA discrimination models. Furthermore, 39 robust age
      dependent markers enabling differentiation among the 6-18-year-old MGL samples
      were discovered. The results were validated by a permutation test and an external
      test set to verify the predictability and reliability of the established
      discrimination models. More importantly, without destroying the MCG roots, the
      proposed approach could also be applied to discriminate MCG root ages indirectly,
      using a minimum amount of homophyletic MGL samples combined with the established
      four PLS-DA models and identified markers. Additionally, to the best of our
      knowledge, this is the first study in which 6-18-year-old MCG root ages have been
      nondestructively differentiated by analyzing homophyletic MGL samples using
      UHPLC/QTOF-MS analysis and two simple successive steps together with four PLS-DA
      models. The method developed in this study can be used as a standard protocol for
      discriminating and predicting MGL ages directly and homophyletic MCG root ages
      indirectly.

PMID- 28437719
TI  - Matrix-assisted laser-desorption/ionization mass spectrometric imaging of
      olanzapine in a single hair using esculetin as a matrix.
AB  - Matrix-assisted laser desorption/ionization-mass spectrometric imaging (MALDI
      MSI) for the analysis of intact hair is a powerful tool for monitoring changes in
      drug consumption. The embedding of a low drug concentration in the hydrophobic
      hair matrix makes it difficult to extract and detect, and requires an improved
      method to increase detection sensitivity. In this study, an MSI method using
      MALDI-Fourier transform ion cyclotron resonance was developed for direct
      identification and imaging of olanzapine in hair samples using the positive ion
      mode. Following decontamination, scalp hair samples from an olanzapine user were
      scraped from the proximal to the distal end three times, and 5mm hair sections
      were fixed onto an Indium-Tin-Oxide (ITO)-coated microscopic glass slide.
      Esculetin (6,7-dihydroxy-2H-chromen-2-one) was used as a new hydrophobic matrix
      to increase the affinity, extraction and ionization efficiency of olanzapine in
      the hair samples. The spatial distribution of olanzapine was observed using five
      single hairs from the same drug user. This matrix improves the affinity of
      olanzapine in hair for molecular imaging with mass spectrometry. This method may
      provide a detection power for olanzapine to the nanogram level per 5mm hair. Time
      course changes in the MSI results were also compared with quantitative HPLC-MS/MS
      for each 5mm segment of single hair shafts selected from the MALDI target. MALDI
      imaging intensities in single hairs showed good semi-quantitative correlation
      with the results from conventional HPLC-MS/MS. MALDI-MSI is suitable for
      monitoring drug intake with a high time resolution.

PMID- 28437720
TI  - Determination of a novel anticancer AMPK activator hernandezine in rat plasma and
      tissues with a validated UHPLC-MS/MS method: Application to pharmacokinetics and
      tissue distribution study.
AB  - Hernandezine, a novel anticancer AMPK activator, is a major active constituent of
      Thalictrum Ranunculaceae. A simple, specific and sensitive liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method has been developed and validated for
      the quantification of hernandezine in rat plasma and tissues after intravenous
      administration. Sample preparation was carried out through a protein
      precipitation extraction with acetonitrile using tetrandrine as internal standard
      (IS). The chromatographic separation was achieved by using an Agilent ZORBAX
      Eclipse Plus C18 column with a mobile phase of acetonitrile and water (containing
      10mM ammonium acetate) in an isocratic elution way. The mass spectrometry (MS)
      analysis was conducted in positive ionization mode with multiple reaction
      monitoring (MRM) transitions at m/z 653.4->411.2 for hernandezine and m/z 623.3
      >381.3 for tetrandrine (IS). Calibration curves were linear over the ranges of
      20.0-4000ng/ml f or both plasma samples and tissue samples (r>0.991). The lower
      limit of quantification (LLOQ) was 20.0ng/ml. The intra-day and inter-day
      precision (RSD%) were less than 14.0%, while the accuracy was ranged from 85.2%
      to 114.9%. Finally, this developed method was successfully applied in the
      pharmacokinetics and tissue distribution study of hernandezine after intravenous
      administration.

PMID- 28437721
TI  - Optimizing follow-up and study retention in the 21st century: Advances from the
      front line in alcohol and tobacco research.
AB  - AIMS: Longitudinal studies are integral in addiction research but retention of
      participants over time can be challenging. While statistical algorithms for
      missing data have advanced, they remain less desirable than collecting actual
      data with high retention rates. An update to methodological primers with
      consideration of evolving technology and privacy concerns is needed for 21st
      century researchers. METHODS: Comprehensive follow-up methodological strategies
      were conducted in four concurrent laboratory- and intervention-based studies
      across N=697 drinker and smokers enrolled in studies at the Clinical Addictions
      Research Laboratory at the University of Chicago. The methods of three key
      longitudinal research themes and their outcomes are outlined, including: a)
      mindset of the research team starting at study enrollment, b) modalities with a
      particular focus on advances in technological strategies in follow-up, and c)
      mitigating difficult to reach and challenging participants. RESULTS: The
      techniques described herein produced follow-up rates of 95% and 99% in two
      laboratory-based studies with follow-ups of 1- and 6-years, respectively and 94%
      and 97% in two intervention studies with follow-ups of 6- and 12- months.
      Adapting incentive strategies more than tripled on-time follow-up, from 18% to
      68% of the sample, switching to more advanced technologies decreased participant
      burden and time by 30% from traditional telephone interviews, and difficult-to
      reach participants averaged 47 contact attempts. CONCLUSIONS: The methods
      presented produced exceptional follow-up retention across four studies. The
      principles and methodologies discussed may be modified across a range of studies
      to target various sub-populations in the addiction field.

PMID- 28437722
TI  - Effective active vaccination against methamphetamine in female rats.
AB  - BACKGROUND: Immunotherapies directed against methamphetamine (MA) abuse have
      shown success in rodent models, however only a limited number of studies have
      investigated active vaccination in female mice and none in female rats. It is
      critical to determine if potential immunotherapeutic strategies generalize across
      sex, particularly for drugs that may produce significant sex-differences on
      behavioral or physiological endpoints. METHODS: Female Wistar rats were initially
      vaccinated with keyhole-limpet hemocyanin (KLH) or an anti-methamphetamine-KLH
      conjugate (MH6-KLH) three times over five weeks and implanted with radiotelemetry
      devices to assess locomotor activity and body temperature responses to MA. Rats
      were first exposed to MA via vapor inhalation (100mg/mL in propylene glycol) and
      then by injection (0.25-1.0mg/kg, i.p.) and vapor after a final vaccine boost.
      RESULTS: The MH6-KLH vaccine generated an increase in antibody titers across the
      initial 6-week, 3 immunization protocol and a restoration of titer after a week
      14 booster. Locomotor stimulation induced by 0.25mg/kg MA, i.p, in the KLH group
      was prevented in the MH6-KLH group. MH6-KLH animals also exhibited an attenuated
      locomotor stimulation produced by 0.5mg/kg MA, i.p. No group differences in
      locomotion induced by vapor inhalation of MA were observed and body temperature
      was not differentially affected by MA across the groups, most likely because
      vapor inhalation of MA that produced similar locomotor stimulation resulted in
      ~10-fold higher plasma MA levels. CONCLUSIONS: This study confirms the efficacy
      of the MH6-KLH vaccine in attenuating the effects of MA in female rats.

PMID- 28437723
TI  - Clinical course and disease burden in patients with paroxysmal nocturnal
      hemoglobinuria by hemolytic status.
AB  - Disease characteristics of patients enrolled in the International PNH Registry
      were assessed during two follow-up periods based on hemolytic status while
      untreated with eculizumab: Non-hemolytic cohort: follow-up time defined as time
      from disease start until last reported untreated lactate dehydrogenase (LDH)
      value <1.5*upper limit normal (ULN); Hemolytic cohort: follow-up time defined as
      time from LDH >=1.5*ULN at or post-disease start, to most recent untreated follow
      up. A total of 1012 patients met criteria for the Non-hemolytic cohort and 1565
      patients for the Hemolytic cohort; median (min, max) years of follow-up were 2.2
      (0.0, 54.2) and 1.2 (0.0, 37.2) years, respectively. Annual rate of thrombotic
      events (TEs) was lower in the Non-hemolytic than Hemolytic cohort (0.01
      events/person-year vs. 0.03 events/person-year; p<0.001). Mortality was lower in
      the Non-hemolytic cohort than the Hemolytic cohort (0.1% (1 death) vs. 1.8% (22
      deaths); p<0.001). While elevated risks for TEs were observed in patients with
      hemolysis, many TEs were also observed in patients without hemolysis. As
      thrombosis is the leading cause of mortality in patients with PNH, this real
      world analysis highlights the importance of awareness and monitoring for TEs in
      patients with PNH regardless of hemolytic status.

PMID- 28437724
TI  - Synthesis of ZnO-nanorod-based materials for antibacterial, antifungal
      activities, DNA cleavage and efficient ultrasound-assisted dyes adsorption.
AB  - Undoped and Au-doped ZnO-nanorods were synthesized in the presence of ultrasound
      and loaded on activated carbon following characterization by X-ray diffraction
      (XRD), scanning electron microscopy (SEM), transmittance electron microscopy
      (TEM), UV-vis spectrophotometry and Fourier transform infrared spectroscopy
      (FTIR). The Au-doped ZnO-nanorod-loaded activated carbon (Au-ZnO-NRs-AC) was used
      for the simultaneous removal of methylene blue (MB) and auramine O (AO) from
      aqueous solutions. Central composite design (CCD) under response surface
      methodology (RSM) was applied to model and optimize the dyes removal versus
      adsorbent mass, pH, and initial dyes concentration and sonication time as well as
      to investigate the possible interaction between these variables. The optimum
      values of the initial MB and AO dyes concentration, adsorbent mass, pH and
      sonication time were found to be 12 and 10mgL-1, 0.0124g, 6.4, and 4min
      respectively. The rapid adsorption process at neutral pH using very small amount
      of the adsorbent makes it promising for the wastewater treatment applications.
      More than 99.5% of both dyes was removed with maximum adsorption capacities in
      binary-component system (107.5 and 95.7mgg-1 for MB and AO, respectively). The
      kinetics and isotherm studies showed that the second-order and Langmuir models
      apply for the kinetics and isotherm of the adsorption of MB and AO on the
      adsorbent used here. Moreover, the wastewater treatment by using an
      antibacterial/antifungal adsorbent makes the process much more valuable.
      Therefore, additional studies were performed which showed efficient
      antibacterial/antifungal activities and DNA cleavage of undoped and Au-doped ZnO
      nanorods as constituent of the adsorbent applied here.

PMID- 28437725
TI  - Evaluation of ecotoxicological effects of benzophenone UV filters: Luminescent
      bacteria toxicity, genotoxicity and hormonal activity.
AB  - The widespread use of organic ultraviolet (UV) filters in personal care products
      raises concerns about their potentially hazardous effects on human and ecosystem
      health. In this study, the toxicities of four commonly used benzophenones (BPs)
      UV filters including benzophenone (BP), 2-Hydroxybenzophenone (2HB), 2-Hydroxy-4
      methoxybenzophenone (BP3), and 2-Hydroxy-4-methoxybenzophenone-5-sulfonicacid
      (BP4) in water were assayed in vitro using Vibrio fischeri, SOS/umu assay, and
      yeast estrogen screen (YES) assay, as well as in vivo using zebrafish larvae. The
      results showed that the luminescent bacteria toxicity, expressed as logEC50,
      increased with the lipophilicity (logKow) of BPs UV filters. Especially, since
      2HB, BP3 and BP4 had different substituent groups, namely -OH, -OCH3 and -SO3H,
      respectively, these substituent functional groups had a major contribution to the
      lipophilicity and acute toxicity of these BPs. Similar tendency was observed for
      the genotoxicity, expressed as the value of induction ratio=1.5. Moreover, all
      the target BPs UV filters showed estrogenic activity, but no significant
      influences of lipophilicity on the estrogenicity were observed, with BP3 having
      the weakest estrogenic efficiency in vitro. Although BP3 displayed no noticeable
      adverse effects in any in vitro assays, multiple hormonal activities were
      observed in zebrafish larvae including estrogenicity, anti-estrogenicity and anti
      androgenicity by regulating the expression of target genes. The results indicated
      potential hazardous effects of BPs UV filters and the importance of the
      combination of toxicological evaluation methods including in vitro and in vivo
      assays.

PMID- 28437726
TI  - Mercury correlates with altered corticosterone but not testosterone or estradiol
      concentrations in common loons.
AB  - We investigated the relation between environmental mercury exposure and
      corticosterone concentrations in free-living adult common loons (Gavia immer). We
      determined blood and feather mercury concentrations and compared them to
      testosterone, estradiol, and stress-induced plasma corticosterone concentrations.
      Although neither testosterone nor estradiol correlated with Hg levels, there was
      a robust positive relation between blood Hg and stress-induced corticosterone
      concentrations in males, but not in females. The lack of an effect in females may
      have been due to overall less contamination in females. There were no significant
      correlations between feather Hg and stress-induced corticosterone in either sex.
      To help determine whether Hg had a causal effect on corticosterone, we
      investigated the impact of experimental Hg intake on the corticosterone stress
      response in captive juvenile loons. Juveniles were subjected to three different
      feeding regimes: 0, 0.4 and 1.2MUg Hg (as MeHgCL)/g wet weight (ww) fish. We then
      measured baseline and 30min post-solitary confinement stressor corticosterone
      concentrations. The Hg fed chicks exhibited a decreased ability to mount a stress
      response. From these data, we conclude that Hg contamination does appear to alter
      the corticosterone response to stress, but not in a consistent predictable
      pattern. Regardless of the direction of change, however, exposure to mercury
      contamination and the resulting impact on the corticosterone stress response in
      common loons may substantially impact health, fitness and survival.

PMID- 28437727
TI  - New inter-correlated genes targeted by diatom-derived polyunsaturated aldehydes
      in the sea urchin Paracentrotus lividus.
AB  - The marine environment is continually subjected to the action of stressors
      (including natural toxins), which represent a constant danger for benthic
      communities. In the present work using network analysis we identified ten genes
      on the basis of associated functions (FOXA, FoxG, GFI-1, nodal, JNK, OneCut/Hnf6,
      TAK1, tcf4, TCF7, VEGF) in the sea urchin Paracentrotus lividus, having key roles
      in different processes, such as embryonic development and asymmetry, cell fate
      specification, cell differentiation and morphogenesis, and skeletogenesis. These
      genes are correlated with three HUB genes, Foxo, Jun and HIF1A. Real Time qPCR
      revealed that during sea urchin embryonic development the expression levels of
      these genes were modulated by three diatom-derived polyunsaturated aldehydes
      (PUAs), decadienal, heptadienal and octadienal. Our findings show how changes in
      gene expression levels may be used as an early indicator of stressful conditions
      in the marine environment. The identification of key genes and the molecular
      pathways in which they are involved represents a fundamental tool in
      understanding how marine organisms try to afford protection against toxicants, to
      avoid deleterious consequences and irreversible damages. The genes identified in
      this work as targets for PUAs can be considered as possible biomarkers to detect
      exposure to different environmental pollutants.

PMID- 28437728
TI  - Is A/A/O process effective in toxicity removal? Case study with coking
      wastewater.
AB  - The anaerobic-anoxic-oxic (A/A/O) process is the commonly used biological
      wastewater treatment process, especially for the coking wastewater. However,
      limit is known about its ability in bio-toxicity removal from wastewater. In this
      study, we evaluated the performance of A/A/O process in bio-toxicity removal from
      the coking wastewater, using two test species (i.e. crustacean (Daphnia magna)
      and zebra fish (Danio rerio)) in respect of acute toxicity, oxidative damage and
      genotoxicity. Our results showed that the acute toxicity of raw influent was
      reduced gradually along with A/A/O process and the effluent presented no acute
      toxicity to Daphnia magna (D. magna) and zebra fish. The reactive oxygen species
      (ROS) level in D. magna and zebra fish was promoted by the effluent from each
      tank of A/A/O process, showing that coking wastewater induced oxidative damage.
      Herein, the oxidative damage to D. magna was mitigated in the oxic tank, while
      the toxicity to zebra fish was reduced in the anoxic tank. The comet assays
      showed that genotoxicity to zebra fish was removed stepwise by A/A/O process,
      although the final effluent still presented genotoxicity to zebra fish. Our
      results indicated that the A/A/O process was efficient in acute toxicity removal,
      but not so effective in the removal of other toxicity (e.g. oxidative damage and
      genotoxicity). Considering the potential risks of wastewater discharge, further
      advanced toxicity mitigation technology should be applied in the conventional
      biological treatment process, and the toxicity index should be introduced in the
      regulation system of wastewater discharge.

PMID- 28437729
TI  - Evaluation of the effects of polymeric chitosan/tripolyphosphate and solid lipid
      nanoparticles on germination of Zea mays, Brassica rapa and Pisum sativum.
AB  - Although the potential toxicity of many metallic and carbon nanoparticles to
      plants has been reported, few studies have evaluated the phytotoxic effects of
      polymeric and solid lipid nanoparticles. The present work described the
      preparation and characterization of chitosan/tripolyphosphate (CS/TPP)
      nanoparticles and solid lipid nanoparticles (SLN) and evaluated the effects of
      different concentrations of these nanoparticles on germination of Zea mays,
      Brassica rapa, and Pisum sativum. CS/TPP nanoparticles presented an average size
      of 233.6+/-12.1nm, polydispersity index (PDI) of 0.30+/-0.02, and zeta potential
      of +21.4+/-1.7mV. SLN showed an average size of 323.25+/-41.4nm, PDI of 0.23+/
      0.103, and zeta potential of -13.25+/-3.2mV. Nanotracking analysis enabled
      determination of concentrations of 1.33*1010 (CS/TPP) and 3.64*1012 (SLN)
      nanoparticles per mL. At high concentrations, CS/TPP nanoparticles caused
      complete inhibition of germination, and thus negatively affected the initial
      growth of all tested species. Differently, SLN presented no phytotoxic effects.
      The different size and composition and the opposite charges of SLN and CS/TPP
      nanoparticles could be associated with the differential phytotoxicity of these
      nanomaterials. The present study reports the phytotoxic potential of polymeric
      CS/TPP nanoparticles towards plants, indicating that further investigation is
      needed on the effects of such formulations intended for future use in
      agricultural systems, in order to avoid damage to the environment.

PMID- 28437730
TI  - The practice of prosecuting child maltreatment: Results of an online survey of
      prosecutors.
AB  - Despite efforts by advocates, practitioners, and legislators to alleviate the
      burden on child maltreatment victims in the criminal justice system, many
      challenges remain for prosecutors as they seek to hold offenders accountable
      while minimizing the emotional impact on children. More than 200 state and local
      prosecutors in 37 states responded to an online survey to share their
      perspectives on current challenges, procedures to support children in the
      adjudication process, and the impact of the U.S. Supreme Court opinion in
      Crawford v. Washington (2004), sex offender registries, and "Safe Harbor"
      legislation to protect child sexual exploitation victims. Respondents' most
      pressing challenges were obtaining evidence to corroborate children's statements
      and the difficulties of working with child victims. Child testimony was ranked as
      more frequent than any other type of evidence, and least frequent were DNA,
      photos or videos of criminal acts, and other physical evidence. Prosecutors rely
      primarily on victim/witness assistants and courtroom tours to prepare children
      for testimony; technological alternatives are seldom used. Results suggest a real
      but limited impact of the Crawford opinion on the need for child testimony and on
      the decision to prosecute. Survey findings indicate a need for greater attention
      to thorough investigations with particular attention to corroboration. Doing so
      may strengthen the child's credibility, which is especially critical in cases
      lacking physical or medical evidence of maltreatment.

PMID- 28437731
TI  - Children and adolescents facing a continuous security threat: Aggressive behavior
      and post-traumatic stress symptoms.
AB  - There is extensive research evidence indicating that children and youth are the
      most vulnerable population for developing psychological symptoms relating to war
      and terror. Although studies have documented a wide range of detrimental
      emotional and behavioral effects of such exposure, much less is known about the
      effects of exposure to a continuous security threat for children and adolescents.
      Against this background, the current article examined the implications of
      continuous exposure to missile attacks among 1096 children and adolescents
      enrolled in public schools near the Israeli border with Gaza. Participants filled
      out quantitative questionnaires, which relate to the pathological consequences of
      continuous exposure to security threats, and to the role of the school and the
      community as a protective environment against disruptive behavior resulting from
      such exposure. The findings revealed that PTSS responses were mainly related to
      the security threat, whereas interpersonal aggression resulted from other types
      of traumatic events. Significant differences were found between aggression and
      posttraumatic symptoms, by age and gender. PTSS was found to be lower for older
      participants and higher for girls, whereas aggression was higher for boys and
      higher for older participants. Furthermore, the sense of belonging to the place
      of residence was negatively associated with PTSS as well as with aggressive
      behavior: the higher the participants' sense of belonging, the lower their levels
      of PTSS and aggressive responses. In contrast, the sense of belonging to the
      school was negatively associated only with aggressive behavior: the higher the
      participants' sense of belonging to the school, the lower their aggressive
      responses. The findings are discussed in the light of trauma theories and in
      light of the results of previous research. The study contributed to knowledge
      about the differential consequences of exposure to a security threat, and
      highlighted the importance of differential interventions with children who show
      post-traumatic symptoms versus those who show aggressive behavior. Accordingly,
      the security situation should not overshadow social issues that need to be
      addressed, such as family violence and aggression among school children.

PMID- 28437732
TI  - Weaving through a cryptic species: Comparing the Neotropical ants Camponotus
      senex and Camponotus textor (Hymenoptera: Formicidae).
AB  - Camponotus senex (Fr. Smith 1858) and Camponotus textor Forel, 1899 are commonly
      confused species in the New World tropics. We provide morphological
      characteristics based on the larvae and adults, behavioural differences, together
      with evidence from molecular markers (cuticular hydrocarbon profiles, venom
      differences, nuclear ribosomal ITS-1, and mtDNA COI sequence comparisons) to
      separate the two species, demonstrating they are not immediately closely related.
      In conclusion we suggest new reliable morphological characters which can benefit
      from deeper phenetic analysis, and support the contextual usefulness of non
      morphological tools in resolving sibling ant species.

PMID- 28437733
TI  - The establishment of in vitro culture and drug screening systems for a newly
      isolated strain of Trypanosoma equiperdum.
AB  - Dourine is caused by Trypanosoma equiperdum via coitus with an infected horse.
      Although dourine is distributed in Equidae worldwide and is listed as an
      internationally important animal disease by the World Organization for Animal
      Health (OIE), no effective treatment strategies have been established. In
      addition, there are no reports on drug discovery, because no drug screening
      system exists for this parasite. A new T. equiperdum strain was recently isolated
      from the genital organ of a stallion that showed typical symptoms of dourine. In
      the present study, we adapted T. equiperdum IVM-t1 from soft agarose media to HMI
      9 liquid media to develop a drug screening assay for T. equiperdum. An
      intracellular ATP-based luciferase assay using CellTiter-Glo reagent and an
      intracellular dehydrogenase activity-based colorimetric assay using WTS-8
      tetrazolium salt (CCK-8 reagent) were used in order to examine the trypanocidal
      effects of each compound. In addition, the IC50 values of 4 reference
      trypanocidal compounds (pentamidine, diminazene, suramin and melarsomine) were
      evaluated and compared using established assays. The IC50 values of these
      reference compounds corresponded well to previous studies involving other strains
      of T. equiperdum. The luciferase assay would be suitable for the mass screening
      of chemical libraries against T. equiperdum because it allows for the simple and
      rapid-evaluation of the trypanocidal activities of test compounds, while a
      simple, inexpensive colorimetric assay will be applicable in developing countries
      for the evaluation of the drug sensitivity of epidemic trypanosome strains.

PMID- 28437734
TI  - IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and
      2040.
AB  - AIM: To produce current estimates of the national, regional and global impact of
      diabetes for 2015 and 2040. METHODS: A systematic literature review was conducted
      to identify data sources on the prevalence of diabetes from studies conducted in
      the period from 1990 to 2015. An analytic hierarchy process was used to select
      the most appropriate studies for each country, and estimates for countries
      without data were modelled using extrapolation from similar countries that had
      available data. A logistic regression model was used to generate smoothed age
      specific estimates, which were applied to UN population estimates. RESULTS: 540
      data sources were reviewed, of which 196 sources from 111 countries were
      selected. In 2015 it was estimated that there were 415 million (uncertainty
      interval: 340-536 million) people with diabetes aged 20-79years, 5.0 million
      deaths attributable to diabetes, and the total global health expenditure due to
      diabetes was estimated at 673 billion US dollars. Three quarters (75%) of those
      with diabetes were living in low- and middle-income countries. The number of
      people with diabetes aged 20-79years was predicted to rise to 642 million
      (uncertainty interval: 521-829 million) by 2040. CONCLUSION: Diabetes prevalence,
      deaths attributable to diabetes, and health expenditure due to diabetes continue
      to rise across the globe with important social, financial and health system
      implications.

PMID- 28437735
TI  - Detective quantum efficiency (DQE) in PET scanners: A simulation study.
AB  - The aim of the present study is to introduce the detective quantum efficiency
      (DQE) for the image quality assessment of positron emission tomography (PET)
      scanners. For this purpose, a thin layer chromatography (TLC) plane source was
      simulated using a previously validated, scanner and source geometry, Monte Carlo
      (MC) model. The model was developed with the Geant4 application for tomographic
      emission (GATE) MC package and reconstructed images obtained with the software
      for tomographic image reconstruction (STIR), with cluster computing. The GE
      Discovery ST PET scanner was simulated by using a previously validated code. A
      plane source consisting of a TLC plate, was simulated by a layer of silica gel on
      aluminum (Al) foil substrate, immersed in 18F-FDG bath solution (1MBq). Image
      quality was assessed in terms of the modulation transfer function (MTF) and the
      normalized noise power spectrum (NNPS) in order to obtain the detective quantum
      efficiency (DQE). MTF curves were estimated from transverse reconstructed images
      of the plane source, whereas the NNPS data were estimated from the corresponding
      coronal images. Images were reconstructed by the maximum likelihood estimation
      ordered subsets maximum a posteriori one step late (MLE)-OS-MAP-OSL algorithm, by
      using various subsets 1-21) and iterations 1-20). MTF values were found to
      increase up to the 12th iteration whereas remain almost constant thereafter.
      However, the range of the increase in the MTF is limited as the number of subsets
      increases. The noise levels were found to increase with the corresponding
      increase of both the number of iterations and subsets. The maximum NNPS value
      (0.517mm2) was observed for the 420 MLEM-equivalent iterations reconstructed
      image at 0cycles/mm. Finally DQE values were found to increase for spatial
      frequencies up to 0.038cycles/mm and to decrease thereafter with the
      corresponding increase in both number of iterations and subsets. The maximum DQE
      value (0.48 at 0.038cycles/mm) was obtained for the 8 MLEM-equivalent iterations
      image. The simulated PET evaluation method based on the TLC plane source can be
      useful in the quality control and in the further development of PET and SPECT
      scanners though GATE simulations.

PMID- 28437737
TI  - Changes in regulatory T cells in patients with ovarian cancer undergoing surgery:
      Preliminary results.
AB  - Regulatory T cells (Treg) suppress immune responses in patients with cancer.
      Surgery is the most effective therapeutic strategy for ovarian cancer (OC).
      However, the interplay between the Treg population and surgical resection remains
      unclear. 61 patients with OC who received no prior treatment were enrolled in the
      study. Treg percentages were characterized from peripheral blood mononuclear
      cells. We investigated CD4+CD25+, CD4+CD25+Foxp3+, CD8+CD28-, and CD8+Foxp3+
      Tregs in OC patients and their postoperative changes using flow cytometry. Treg
      percentages were significantly higher in OC patients than those in benign ovarian
      tumors (BOT) and healthy controls. Higher percentages of Tregs were found in
      patients with stage III/IV than stage I/II OC. Treg percentages were
      significantly decreased postoperatively. The postoperative Treg percentages in
      patients with stage I/II OC were similar to those in BOT patients, while
      postoperative Treg percentages in patients with stage III/IV OC remained higher.
      Tregs were markedly lower on postoperative day (POD) 3 than preoperatively. They
      increased slightly after 7days, but remained lower than preoperative levels.
      These data suggested that Tregs continued to decline from POD 7 to POD 30. Treg
      percentages are correlated with the tumor burden and could be a key factor in
      monitoring the immunological status of patients with OC.

PMID- 28437736
TI  - Murine diet-induced obesity remodels cardiac and liver mitochondrial phospholipid
      acyl chains with differential effects on respiratory enzyme activity.
AB  - Cardiac phospholipids, notably cardiolipin, undergo acyl chain remodeling and/or
      loss of content in aging and cardiovascular diseases, which is postulated to
      mechanistically impair mitochondrial function. Less is known about how diet
      induced obesity influences cardiac phospholipid acyl chain composition and thus
      mitochondrial responses. Here we first tested if a high fat diet remodeled murine
      cardiac mitochondrial phospholipid acyl chain composition and consequently
      disrupted membrane packing, supercomplex formation and respiratory enzyme
      activity. Mass spectrometry analyses revealed that mice consuming a high fat diet
      displayed 0.8-3.3 fold changes in cardiac acyl chain remodeling of cardiolipin,
      phosphatidylcholine, and phosphatidylethanolamine. Biophysical analysis of
      monolayers constructed from mitochondrial phospholipids of obese mice showed
      impairment in the packing properties of the membrane compared to lean mice.
      However, the high fat diet, relative to the lean controls, had no influence on
      cardiac mitochondrial supercomplex formation, respiratory enzyme activity, and
      even respiration. To determine if the effects were tissue specific, we
      subsequently conducted select studies with liver tissue. Compared to the control
      diet, the high fat diet remodeled liver mitochondrial phospholipid acyl chain
      composition by 0.6-5.3-fold with notable increases in n-6 and n-3
      polyunsaturation. The remodeling in the liver was accompanied by diminished
      complex I to III respiratory enzyme activity by 3.5-fold. Finally, qRT-PCR
      analyses demonstrated an upregulation of liver mRNA levels of tafazzin, which
      contributes to cardiolipin remodeling. Altogether, these results demonstrate that
      diet-induced obesity remodels acyl chains in the mitochondrial phospholipidome
      and exerts tissue specific impairments of respiratory enzyme activity.

PMID- 28437738
TI  - Simultaneous spectrophotometric determination of glimepiride and pioglitazone in
      binary mixture and combined dosage form using chemometric-assisted techniques.
AB  - In the present work, pioglitazone and glimepiride, 2 widely used antidiabetics,
      were simultaneously determined by a chemometric-assisted UV-spectrophotometric
      method which was applied to a binary synthetic mixture and a pharmaceutical
      preparation containing both drugs. Three chemometric techniques - Concentration
      residual augmented classical least-squares (CRACLS), principal component
      regression (PCR), and partial least-squares (PLS) were implemented by using the
      synthetic mixtures containing the two drugs in acetonitrile. The absorbance data
      matrix corresponding to the concentration data matrix was obtained by the
      measurements of absorbencies in the range between 215 and 235nm in the intervals
      with Deltalambda=0.4nm in their zero-order spectra. Then, calibration or
      regression was obtained by using the absorbance data matrix and concentration
      data matrix for the prediction of the unknown concentrations of pioglitazone and
      glimepiride in their mixtures. The described techniques have been validated by
      analyzing synthetic mixtures containing the two drugs showing good mean recovery
      values lying between 98 and 100%. In addition, accuracy and precision of the
      three methods have been assured by recovery values lying between 98 and 102% and
      R.S.D. % ?0.6 for intra-day precision and ?1.2 for inter-day precision. The
      proposed chemometric techniques were successfully applied to a pharmaceutical
      preparation containing a combination of pioglitazone and glimepiride in the ratio
      of 30: 4, showing good recovery values. Finally, statistical analysis was carried
      out to add a value to the verification of the proposed methods. It was carried
      out by an intrinsic comparison between the 3 chemometric techniques and by
      comparing values of present methods with those obtained by implementing reference
      pharmacopeial methods for each of pioglitazone and glimepiride.

PMID- 28437739
TI  - Experimental study on evaluation and optimization of tilt angle of parallel-plate
      electrodes using electrocoagulation device for oily water demulsification.
AB  - Tilt angle of parallel-plate electrodes (APE) is very important as it improves
      the economy of diffusion controlled Electrocoagulation (EC) processes. This study
      aimed to evaluate and optimize APE of a self-made EC device including integrally
      rotary electrodes, at a fixed current density of 120 Am-2. The APEs investigated
      in this study were selected at 0 degrees , 30 degrees , 45 degrees , 60 degrees ,
      90 degrees , and a special value (alpha(d)) which was defined as a special
      orientation of electrode when the upper end of anode and the lower end of cathode
      is in a line vertical to the bottom of reactor. Experiments were conducted to
      determine the optimum APE for demulsification process using four evaluation
      indexes, as: oil removal efficiency in the center between electrodes; energy
      consumption and Al consumption, and besides, a novel universal evaluation index
      named as evenness index of oil removal efficiency employed to fully reflect
      distribution characteristics of demulsification efficiency. At a given plate
      spacing of 4 cm, the optimal APE was found to be alpha(d) because of its
      potential of enhancing the mass transfer process within whole EC reactor without
      addition, external mechanical stirring energy, and finally the four evaluation
      indexed are 97.07%, 0.11 g Al g-1 oil, 2.99 kwhkg-1 oil, 99.97% and 99.97%,
      respectively.

PMID- 28437740
TI  - Stabilization of metal(loid)s in two contaminated agricultural soils: Comparing
      biochar to its non-pyrolysed source material.
AB  - Two metal(loid) contaminated agricultural soils were amended with grape stalk
      (wine production by-product)-derived biochar as well as its pre-pyrolysed origin
      material, to investigate their geochemical impacts on As, Cr, Cu and Zn. Detailed
      physico-chemical evaluation combined with a column leaching test determined the
      retention of metal(loid)s from soil solution by each amendments. A pot experiment
      measured metal(loid)s in soil pore water and their uptake to ryegrass when the
      amendments were mixed into soils at 1 and 5% (w/w). Total Cr and Zn
      concentrations were reduced furthest in column leachates by the addition of raw
      material and biochar respectively, compared to the untreated soil; Cr(III) was
      the predominant specie initially due to rapid acidification of leachates and
      organic complexation resulting from raw material addition. Loadings of
      metal(loid)s to the amendments recovered from the post-leached columns were in
      the order Cu " Zn > Cr ~ As. In the pot test ryegrass Cr uptake was initiated by
      the addition of both amendments, compared to the untreated soil, whereas only
      biochar addition resulted in significant increases in Zn uptake, explained by its
      significant enhancement of ryegrass biomass yield, especially at 5% dosage; raw
      material addition significantly decreased biomass yields. Inconsistent
      relationships between pore water parameters and ryegrass uptake were common to
      both soils investigated. Therefore, whilst both amendments modified soil
      metal(loid) geochemistry, their effects differed fundamentally; in environmental
      risk management terms these results highlight the need to investigate the
      detailed geochemical response of contaminated soils to diverse organic amendment
      additions.

PMID- 28437741
TI  - Use of nuclear receptor luciferase-based bioassays to detect endocrine active
      chemicals in a biosolids-biochar amended soil.
AB  - Biosolids are a potentially valuable source of carbon and nutrients for
      agricultural soils; however, potential unintended impacts on human health and the
      environment must be considered. Virtually all biosolids contain trace amounts
      endocrine-disrupting chemicals derived from human use of pharmaceuticals and
      personal care products (PPCPs). One potential way to reduce the bioavailability
      of PPCPs is to co-apply biosolids with biochar to soil, because biochar's
      chemical (e.g., aromaticity) and physical properties (e.g., surface area) give it
      a high affinity to bind many organic chemicals in the environment. We developed a
      soil-specific extraction method and utilized a luciferase-based bioassay (CALUX)
      to detect endocrine active chemicals in a biosolids-biochar co-amendment soil
      greenhouse study. Both biochar (walnut shell, 900  degrees C) and biosolids had
      positive impacts on carrot and lettuce biomass accumulation over our study
      period. However, the walnut shell biochar stimulated aryl hydrocarbon receptor
      activity, suggesting the presence of potential endocrine active chemicals in the
      biochar. Since the biochar rate tested (100 t ha-1) is above the average
      agronomic rate (10-20 t ha-1), endocrine effects would not be expected in most
      environmental applications. The effect of high temperature biochars on endocrine
      system pathways must be explored further, using both quantitative analytical
      tools to identify potential endocrine active chemicals and highly sensitive
      bioanalytical assays such as CALUX to measure the resulting biological activity
      of such compounds.

PMID- 28437742
TI  - Biological treatment of model dyes and textile wastewaters.
AB  - Previous works conducted in our laboratory, reveled that Bacillus aryabhattai
      DC100 produce ligninolytic enzymes such as laccases and/or peroxidases, opening
      new applications in different bioprocesses, including the treatment of disposal
      residues such as dyestuffs from textile processing industries. This work
      described the degradation of three commercial model dyes Coomassie Brilliant Blue
      G-250 (CBB), Indigo Carmine (IC) and Remazol Brilliant Blue R (RBBR) under
      different culture media and operational conditions. The process was optimized
      using a Central Composite Rotatable Design, and the desirability predicted
      complete decolorization of 150 mg/L CBB at 37  degrees C, 304.09 rpm and salt
      concentration of 19.204 g/L. The model was validated with concentrations up to
      180 mg/L CBB and IC, not being able to remove high amount of RBBR. The procedure
      here developed also allowed Chemical Oxygen Demands (COD) reductions in CBB of
      about 42%, meanwhile tests on real effluents from a local textile industry
      involved COD reductions of 50% in a liquid wastewater and 14% in semi-liquid
      sludge. Thus, allow the authorized discharge of wastewater into the corresponding
      treatment plant. Decolorization efficiencies and COD reductions open on the
      potential application of B. aryabhattai DC100 on the bioremediation of real
      effluents from textile industries.

PMID- 28437743
TI  - Eco-pharmacovigilance of non-steroidal anti-inflammatory drugs: Necessity and
      opportunities.
AB  - Eco-pharmacovigilance (EPV) is a practical and powerful approach to minimize the
      potential risks posed by pharmaceutical residues in environment. However, it is
      impracticable to practise rigorous and unitary EPV process for all the existing
      and new pharmaceuticals. Here, we focused on non-steroidal anti-inflammatory
      drugs (NSAIDs), and discussed the necessity and potential opportunities of
      practising EPV of NSAIDs. We found that the consumption of NSAIDs is huge and
      ubiquitous across the globe. NSAIDs were worldwidely reported as one of the most
      dominant and frequently detected groups in environmental matrices including
      wastewater, surface water, suspended solids, sediments, groundwater, even
      drinking water. Besides, there is definitive evidence for the adverse impacts of
      NSAID residues on scavenging birds and aquatic species. These data suggested the
      necessity of implementing EPV of NSAIDs. From the perspective of drug
      administration, we identified some things that can be done as management practice
      options for EPV implementation on NSAIDs.

PMID- 28437744
TI  - Fe(III) ions enhanced catalytic properties of (BiO)2CO3 nanowires and mechanism
      study for complete degradation of xanthate.
AB  - The wire-like Fe3+-doped (BiO)2CO3 photocatalyst was synthesized by a
      hydrothermal method. The photocatalytic property of Fe3+-doped (BiO)2CO3
      nanowires was evaluated through degradation of sodium isopropyl xanthate under UV
      visible light irradiation. The as-prepared Fe3+-doped (BiO)2CO3 nanowires were
      characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), UV
      visible diffuse reflectance spectroscopy (UV-vis DRS), X-ray photoelectron
      spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) in detail.
      The results of XRD showed that the crystallinity of (BiO)2CO3 nanowires decreased
      when Fe3+ ions were introduced into the solution system. XPS results illustrated
      that xanthate could be absorbed on the surface of Fe3+-doped (BiO)2CO3 nanowires
      to produce BiS bond at the beginning of the reaction, which could broaden the
      visible light absorption. FTIR spectra confirmed the formation of SO42- after
      photocatalytic decomposition of xanthate solution. The Fe3+-doped (BiO)2CO3
      nanowires showed an enhanced photocatalytic activity for decomposition of
      xanthate due to the narrower band gap and larger BET surface area, comparing with
      pure (BiO)2CO3 nanowires. By the results of UV-vis spectra of the solution and
      FTIR spectra of recycled Fe3+-doped (BiO)2CO3, the xanthate was oxidized
      completely into CO2 and SO42-. The photocatalytic degradation process of xanthate
      followed a pseudo-second-order kinetics model. The mechanism of enhanced
      photocatalytic activity was proposed as well.

PMID- 28437745
TI  - Comparative study of the effects of gadolinium chloride and gadolinium - based
      magnetic resonance imaging contrast agent on freshwater mussel, Dreissena
      polymorpha.
AB  - Gadolinium (Gd), a metal of the lanthanide series used in various industrial and
      medical purposes is released into the aquatic environment. However, there are few
      aquatic toxicological studies addressing environmental effects of Gd which
      remains unknown in aquatic animals. Therefore, this study aimed to compare the
      effects of GdCl3 and a gadolinium-based MRI contrast agent (Omniscan), in zebra
      mussels after 28 days through a multibiomarker approach. Data revealed that after
      GdCl3 exposure, the mRNA level of metallothionein (MT) was modulated, those of
      cytochrome c oxidase (CO1) and superoxide dismutase (SOD) were increased, while
      gene expressions of catalase (CAT) and glutathione-S-transferase (GST) were
      downregulated. Furthermore, neither lipoperoxidation (LPO) nor genotoxicity were
      detected but only a decrease in the cyclooxygenase (COX) activity was observed.
      In addition, a significant correlation was found between biomarkers and
      bioaccumulated Gd, suggesting that mitochondrial and anti-inflammatory pathways
      were triggered with GdCl3. By opposition, the contrasting agent formulation
      induced downregulation of SOD, CAT, GST and CO1, a decrease in the level of LPO
      and an increase in the GST and COX activities. This suggests that the chelated
      form of Gd did not promote reactive oxygen species (ROS) production and exhibits
      antioxidant and proinflammatory effects in mussels. Therefore, this study
      revealed that ionic and the chelated form of Gd influence different cellular
      pathways to initiate cellular changes.

PMID- 28437746
TI  - Catalytic reduction of 4-nitrophenol and photo inhibition of Pseudomonas
      aeruginosa using gold nanoparticles as photocatalyst.
AB  - A simple, green method is described for the synthesis of Gold (Au) nanoparticles
      (NPs) using Cotoneaster horizontalis extract as a phyto-reducer and capping agent
      with superior photo inhibition activity against Pseudomonas aeruginosa. Different
      from the other methods used elevated temperatures for nanoparticles synthesis,
      the novelty of our method lies in its energy saving process and fast synthesis
      rates (~5min for AuNPs), and its potential to tune the nanoparticles size and
      afterward their catalytic activity. The starch, fatty acid and reducing sugars
      present in the extract are mostly responsible for repaid reduction rate Au+3 ions
      to AuNPs. Strong Plasmon resonance (SPR) of AuNPs was observed at 560nm, which
      indicates the formation of gold nanoparticles. Uv-visible spectroscopy, high
      resolution transmission electron microscope (HRTEM) and energy dispersion X-ray
      diffraction (XRD) were preformed to find out the formation of AuNPs. Proficient
      reduction of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) in the presence of
      AuNPs and NaBH4 was observed and was found to depend upon the nanoparticle size
      or the extract concentration. The AuNPs was also evaluated for antibacterial
      against P. aeruginosa. Before transferred it into antibacterial activity, it
      placed under visible light for 120min. The same experiment was performed in dark
      as control medium. The photo irradiated AuNPs was observed to be more effective
      against P. aeruginosa. The result showed that diameter of zone of inhibition of
      visible light irradiated AuNPs against P. aeruginosa was 17 (+/-0.5) and in dark
      was 8 (+/-0.4) mm.

PMID- 28437747
TI  - Concurrent evaluation of personal damaging and beneficial UV exposures over an
      extended period.
AB  - Personal exposure to solar ultraviolet radiation (UVR) is acknowledged as having
      both positive and negative effects on human health. This study aimed to measure
      concurrently the personal erythemal UV, UVA and vitamin D effective exposures of
      participants in each season of a year. Participants were all indoor office
      workers located at two different sites less than 6.5 km apart at the sub-tropical
      location of Toowoomba (27 degrees 33'S 151 degrees 55'E). The subjects wore a
      combined dosimeter badge horizontally on the shoulder for a minimum of one week
      in each season; this badge used 8-methoxypsoralen film to record the UVA waveband
      and polyphenylene oxide film for the erythemal and the vitamin D effective UV
      wavebands. The results show that median erythemal exposure was highest during the
      spring and lowest during winter, as was the vitamin D effective exposure. Median
      UVA exposures were at a similar level in winter and summer, autumn was higher
      (double) and spring at a lower level. The duration and time of day participants
      spent outdoors changed in each season; in winter, participants spent an average
      of 101 minutes outdoors between 10:00-14:00 h over the week, whereas in summer
      this fell to 79 minutes even though they were outdoors more often. The daily
      UVA/UVB ratio is lowest between 10:00-14:00 h and also changes with the season
      resulting in the differences between the distributions of exposure for each of
      the wavebands. Each category of exposures must be assessed individually as each
      season and each waveband has different distributions. The results also
      demonstrate that the dual film dosimeter developed and characterized with a
      calibration to three different biological responses, is an effective device for
      the concurrent measurement of erythemal UV, UVA and vitamin D effective UV
      exposures for periods of up to seven days.

PMID- 28437748
TI  - Rational and timely haemostatic interventions following cardiac surgery -
      coagulation factor concentrates or blood bank products.
AB  - BACKGROUND: Cardiac surgery may cause a serious coagulopathy leading to increased
      risk of bleeding and transfusion demands. Blood bank products are commonly first
      line haemostatic intervention, but has been associated with hazardous side
      effect. Coagulation factor concentrates may be a more efficient, predictable, and
      potentially a safer treatment, although prospective clinical trials are needed to
      further explore these hypotheses. This study investigated the haemostatic
      potential of ex vivo supplementation of coagulation factor concentrates versus
      blood bank products on blood samples drawn from patients undergoing cardiac
      surgery. METHODS: 30 adults were prospectively enrolled (mean age=63.9,
      females=27%). Ex vivo haemostatic interventions (monotherapy or combinations)
      were performed in whole blood taken immediately after surgery and two hours
      postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen
      concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa
      (rFVIIa) were investigated. The haemostatic effect was evaluated using whole
      blood thromboelastometry parameters, as well as by thrombin generation. RESULTS:
      Immediately after surgery the compromised maximum clot firmness was corrected by
      monotherapy with fibrinogen or platelets or combination therapy with fibrinogen.
      At two hours postoperatively the coagulation profile was further deranged as
      illustrated by a prolonged clotting time, a reduced maximum velocity and further
      diminished maximum clot firmness. The thrombin lagtime was progressively
      prolonged and both peak thrombin and endogenous thrombin potential were
      compromised. No monotherapy effectively corrected all haemostatic abnormalities.
      The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood
      bank products were not as effective in the correction of the coagulopathy.
      CONCLUSION: Coagulation factor concentrates appear to provide a more optimal
      haemostasis profile following cardiac surgery compared to blood bank products.

PMID- 28437749
TI  - Epilepsy awareness and emergency rescue training: Ignorance is bliss!
AB  - Status epilepticus (SE) has a high mortality rate and is associated with
      complications such as neurological deficit and cognitive decline. Buccal
      midazolam is the recommended emergency rescue medication in the UK to reduce the
      duration of a seizure and SE. It should be administered by an appropriately
      trained person. There are agreed guidelines on training standards for its
      administration in the UK produced by the Joint Epilepsy Council of the United
      Kingdom and Ireland. Training should provide an overview of epilepsy to
      facilitate safe, person-centered care and appropriate administration of rescue
      medication to people with epilepsy (PWE). Unfortunately the current guidelines do
      not assure satisfactory practice. An investigation was conducted to quantify the
      nature and degree of the problem in Cornwall, UK (population 550,000). To address
      the identified inconsistencies, a web-based test was developed using a focus
      group of experts and stakeholders. Over 800 carers for PWE took the test at
      different intervals of its development. A consistent 20% failure rate was noted.
      Over 90% of participants felt it kept PWE safer. The test was incorporated into
      routine clinical practice and has contributed to reduction of primary epilepsy
      deaths. The e-test is a cost-effective solution to help harmonize practices
      across different settings and can be easily adopted by other countries.

PMID- 28437750
TI  - Becoming comfortable with "my" epilepsy: Strategies that patients use in the
      journey from diagnosis to acceptance and disclosure.
AB  - OBJECTIVE: Proponents of resilience theory have highlighted the importance of
      understanding the processes of resilience. The objective of the study was to
      explore how people with epilepsy reach a stage of being comfortable with their
      epilepsy. Identifying the processes used is important to developing effective
      self-management for people who are newly diagnosed with epilepsy. METHOD: A
      grounded theory approach involving forty-nine consenting adult people with
      epilepsy (18 years and over), was used to explore their first-hand experiences of
      coming to terms with their epilepsy. Data were collected using one-to-one
      interview to elicit in-depth personal accounts of people with epilepsy's
      experiences of adjusting to their diagnosis of epilepsy. Using grounded theory's
      systematic inductive-deductive process data of analysis, the core findings that
      emerged from the open coding and inductive phase were analyzed independently by
      two researchers to ensure that findings were verified and validated across the
      interview dataset. FINDINGS: Three core categories emerged as central to the
      journey that people experience after receiving their diagnosis of epilepsy
      towards becoming comfortable with their epilepsy. These were: i) meaning of "my"
      epilepsy diagnosis, to capture people with epilepsy's feelings, reactions and
      concerns after being diagnosed with epilepsy, ii) useful strategies, to identify
      what people with epilepsy did to become comfortable with their diagnosis, and
      iii) being comfortable with my epilepsy, to account for the frame of mind of
      people with epilepsy when they reach a point of accepting their diagnosis.
      DISCUSSION: The findings provide important insights into the personal experiences
      of people with epilepsy after receiving their diagnosis and identifies a range of
      strategies they find useful in helping them reach a position of acceptance and
      being 'comfortable with my epilepsy'.

PMID- 28437751
TI  - Effects of picrotoxin on zebrafish larvae behaviors: A comparison study with PTZ.
AB  - Larval zebrafish (Danio rerio) have been suggested as a high-throughput
      experimental animal model for epilepsy-related genetic and developmental studies.
      The behavioral manifestations in response to the seizure-inducing drugs
      picrotoxin (PTX) (1, 5, 25, 125, or 625MUM) or pentylenetetrazole (PTZ) (1, 2, 4,
      8, or 16mM) under light-dark conditions were studied using zebrafish larvae at
      5days post-fertilization (dpf). Two behavioral parameters, locomotor activity and
      thigmotaxis behavior, were analyzed. We conclude that high concentrations of PTX
      treatment increased locomotion and thigmotaxis in 5 dpf zebrafish larvae under
      continuous illumination and the locomotion of PTX-treated zebrafish was decreased
      under the dark condition. High concentrations of PTX treatment also increased
      thigmotaxis (an indicator of increased anxiety levels) in zebrafish larvae under
      both continuous illumination and dark condition. PTZ treatment increased the
      locomotion of 5 dpf zebrafish larvae under continuous illumination. However, 2mM
      PTZ decreased locomotion, and high concentrations of PTZ decreased the locomotion
      of larvae under dark conditions. High concentrations of PTZ treatment also
      increased thigmotaxis in the zebrafish larvae under both continuous illumination
      and dark condition. Compared with PTZ, PTX leads to higher levels of movement
      under light conditions and lower levels of movement under dark condition.
      However, the level of thigmotaxis in the zebrafish larvae was similar between the
      two drug treatments.

PMID- 28437752
TI  - DNA repair and damage pathways in breast cancer development and therapy.
AB  - DNA damage/repair constitutes several key pathways working in concert to
      eliminate DNA lesions and maintain genome stability and integrity. Defective
      components in DNA damage and repair machinery are an underlying cause for the
      development and progression of different types of cancers, and breast cancer is
      no exception. In this paper, we will briefly explain the importance of DNA damage
      and repair, introduce the current classification schemes for breast cancer, and
      review the known defects in the repair machinery that have been associated with
      the risk of breast cancer. Finally, we discuss how the understanding of these
      pathways can help to design therapeutics for specific targeting of breast cancer
      tumors.

PMID- 28437753
TI  - P-gp modulatory acetyl-11-keto-beta-boswellic acid based nanoemulsified carrier
      system for augmented oral chemotherapy of docetaxel.
AB  - In spite of being a very potent and promising drug against many types of cancer,
      docetaxel suffers the disadvantage of low solubility and poor bioavailability
      rendering it unsuitable for oral administration. Also, the available marketed
      formulation for intravenous administration has its inherent drawbacks owing to
      the presence of polysorbate 80. Here, we exploited the anticancer and P-gp
      inhibitory potential of naturally occurring frankincense oil to fabricate a
      stable docetaxel loaded nanoemulsified carrier system for oral delivery. The
      nanoemulsion possessing desirable particle size (122+/-12nm), polydispersity
      (0.086+/-0.007) and zeta potential (-29.8+/-2.1mV) was stable against all type of
      physical stresses and simulated physiological conditions tested. The formulation
      showed higher uptake in Caco-2 cells and inhibited P-gp transporter significantly
      (P<0.05). In MDA-MB-231 cells, it showed less IC50, arrested cells in G2-M phase
      and exhibited higher degree of apoptosis than marketed formulation Taxotere(r).
      The 182.58+/-4.16% increment in relative oral bioavailability led to higher in
      vivo anti-proliferative activity manifesting 19% more inhibition than
      Taxotere(r). Conclusively, it is revealed that the developed nanoemulsion will be
      a propitious approach towards alternative docetaxel therapy.

PMID- 28437754
TI  - Ion concentration effect (Na+ and Cl-) on lipid vesicle formation.
AB  - Lipid vesicle formation is known to be suppressed in salt solutions, but the
      mechanism of this phenomenon remains unclear. In order to better understand this
      issue, the effect of salt concentrations (0-800mM) of sodium chloride on the
      behavior of L-alpha-phosphatidylcholine (PC) in aqueous solution was investigated
      in this work. The results showed that fusion among vesicles, micelles and
      bilayers may be essential for vesicle formation. With addition of ions and an
      increase in ion concentration, the lipids became constrained in lateral movement
      and packed increasingly tightly. The resulted hard supported phospholipid
      bilayers (SPBs) were thus more difficult to detach from the substrate to form
      vesicles. These phenomena were tried to be explained at molecular level.
      Hydrophobic effect is the original cause of lipid vesicle formation, which in
      fact is absence of attraction between the involved substances. That is to say,
      the stronger the 3D network was bounded in the medium, the stronger the
      hydrophobic repulsion on the lipids would be. This might be one reason for the
      suppression of vesicle formation in salt solution.

PMID- 28437755
TI  - An in vitro study of cartilage-meniscus tribology to understand the changes
      caused by a meniscus implant.
AB  - Active lifestyles increase the risk of meniscal injury. A permanent meniscus
      implant of polycarbonate urethane (PCU) is a promising treatment to
      postpone/prevent total knee arthroplasty. Study of the changes in articular
      cartilage tribology in the presence of PCU is essential in developing the optimum
      meniscus implant. Therefore, a cartilage-meniscus reciprocating, sliding model
      was developed in vitro, mimicking the stance and swing phases of the gait cycle.
      The meniscus was further replaced with PCU and surface-modified PCUs (with C18
      chains, mono-functional polydimethylsiloxane groups and mono-functional
      polytetrafluoroethylene groups) to study the changes. The coefficient of friction
      (COF) was calculated, and cartilage wear was determined and quantified
      histologically. The cartilage-meniscus sliding resulted in low COF during both
      stance and swing (0.01< COF <0.12) and low wear of cartilage (scores <1). The
      cartilage-PCU sliding, during stance, revealed similar low COFs. But during
      swing, the COFs were high (average ~1, maximum 1.6), indicating a breakdown in
      interstitial fluid pressurization lubrication and non-effective activation of the
      boundary lubrication. This may lead to wear of cartilage in long term. However,
      under the tested conditions the wear of cartilage against PCUs was not higher
      than its wear against meniscus, and the cartilage was occasionally damaged. The
      COF decreased with increasing the contact pressure (as-per a power equation) up
      to 1MPa. The changes in the surface modification of PCU did not affect PCU's
      tribological performance.

PMID- 28437756
TI  - Local dynamic stability and gait variability during attentional tasks in young
      adults.
AB  - Cell phone use while walking may be a cognitive distraction and reduce visual and
      motor attention. Thus, the aim of this study was to verify the effects of
      attentional dual-tasks while using a cell phone in different conditions.
      Stability, regularity, and linear variability of trunk kinematics, and gait
      spatiotemporal parameters in young adults were measured. Twenty young subjects of
      both genders were asked to walk on a treadmill for 4min under the following
      conditions: (a) looking forward at a fixed target 2.5m away (walking); (b)
      talking on a cell phone with unilateral handling (talking); (c) texting messages
      on a cell phone with unilateral handling (texting); and (d) looking forward at
      the aforementioned target while listening to music without handling the phone
      (listening). Local dynamic stability measured in terms of the largest Lyapunov
      exponent decreased while handling a cell phone (talking and texting). Gait
      variability and regularity increased when talking on a cell phone, but no
      variable changed in the listening condition. Under all dual-task conditions,
      there were significant increases in stride width and its variability. We conclude
      that young adults who use a cell phone when walking adapt their gait pattern
      conservatively, which can be because of increased attentional demand during cell
      phone use.

PMID- 28437757
TI  - Abnormal loading and functional deficits are present in both limbs before and
      after unilateral knee arthroplasty.
AB  - Unilateral knee replacement is often followed by a contralateral replacement in
      time and the biomechanics of the other knee before and after knee replacement
      remains poorly understood. The aim of this paper is to distinguish the features
      of arthritic gait in the affected and unaffected legs relative to a normal
      population and to assess the objective recovery of gait function post
      operatively, with the aim of defining patients at risk of poor post-operative
      function. Twenty patients with severe knee OA but no pain or deformity in any
      other lower limb joint were compared to twenty healthy subjects of the same age.
      Gait analysis was performed and quadriceps and hamstrings co-contraction was
      measured. Fifteen subjects returned 1year following knee arthroplasty. Moments
      and impulses were calculated, principal component analysis was used to analyse
      the waveforms and a classification technique (the Cardiff Classifier) was used to
      select the most discriminant data and define functional performance. Comparing
      pre-operative function to healthy function, classification accuracies for the
      affected and unaffected knees were 95% and 92.5% respectively. Post-operatively,
      the affected limb returned to the normal half of the classifier in 8 patients,
      and 7 of those patients returned to normal function in the unaffected limb.
      Recovery of normal gait could be correctly predicted 13 out of 15 times at the
      affected knee, and 12 out of 15 times at the unaffected knee based on pre
      operative gait function. Focused rehabilitation prior to surgery may be
      beneficial to optimise outcomes and protect the other joints following knee
      arthroplasty.

PMID- 28437758
TI  - Balance impairment in kidney transplant recipients without concurrent peripheral
      neuropathy.
AB  - Kidney transplant recipients (KTRs) present with compromised functional capacity,
      low levels of physical activity, muscle atrophy, and peripheral nerve dysfunction
      that may result in high postural instability. This study aimed to compare the
      static balance control of 19 KTRs with 19 healthy adults (HA). All participants
      completed the Romberg test on a stabilometric platform with eyes open (EO), eyes
      closed (EC) and during a dual task (DT) condition. Centre of pressure (COP)
      measures (COP velocity (COPv) and sway area (SA)), as well as position-based
      outcomes such as anterior-posterior (AP) and medio-lateral (ML) ranges of COP
      displacements were recorded. Independent ANCOVA revealed an overall lower
      performance of KTRs compared to HA (p<0.05) with the EC condition exhibiting the
      worst relative performance for KTRs, suggesting a poorer capacity of relying on
      proprioceptive information when maintaining the upright posture. The addition of
      a cognitive task did not further worsen balance performance in KTRs. As impaired
      postural control is one of the main predictors of falls in elderly subjects,
      these data might also indicate that this constitutes an equivalent risk factor
      for falling in middle-aged KTRs.

PMID- 28437759
TI  - Correlation of technical surgical goals to the GDI and investigation of post
      operative GDI change in children with cerebral palsy.
AB  - AIM: The purpose of this study was to introduce a standardized set of surgical
      technical achievement goals (TAGs) as part of a comprehensive outcome assessment
      model for children with spastic cerebral palsy (CP) undergoing orthopaedic
      surgical intervention to improve gait. Examination of relationships of these
      surgical goals to the Gait Deviation Index (GDI) and use of two assessments in
      tandem provided a thorough picture of technical surgical outcomes. This study
      also investigated changes in GDI in children with spastic CP after surgery.
      METHODS: Data from 269 participants with spastic CP, aged 4 to 19 years with
      Gross Motor Function Classification System (GMFCS) levels I, II, and III who
      underwent lower extremity orthopaedic surgical intervention to improve gait were
      retrospectively analyzed. Data were examined as one heterogeneous group and sub
      grouped based on pattern of involvement and GMFCS level to determine change in
      GDI and relationships between GDI and TAGs. RESULTS: Differences in TAG
      achievement and GDI change by GMFCS level suggest a pairing of GDI with another
      technical measure to be beneficial. Analysis of the outcome tools individually
      revealed a significant difference between the pre-operative GDI and post
      operative GDI mean for the entire group, as well as each of the subgroups. A
      significant difference in TAG achievement by GMFCS level was also noted.
      CONCLUSION: This paper provides evidence that lower extremity orthopedic
      intervention for the ambulatory child with spastic diplegic or hemiplegic CP
      improves gait and that a pairing of the GDI and TAGs system is beneficial to
      capture an accurate technical outcome assessment in both higher and lower
      functioning patients.

PMID- 28437760
TI  - The effects of object height and visual information on the control of obstacle
      crossing during locomotion in healthy older adults.
AB  - In order to safely avoid obstacles, humans must rely on visual information
      regarding the position and shape of the object obtained in advance. The present
      study aimed to reveal the duration of obstacle visibility necessary for
      appropriate visuomotor control during obstacle avoidance in healthy older adults.
      Participants included 13 healthy young women (mean age: 21.5+/-1.4years) and 15
      healthy older women (mean age: 68.5+/-3.5years) who were instructed to cross over
      an obstacle along a pressure-sensitive pathway at a self-selected pace while
      wearing liquid crystal shutter goggles. Participants were evaluated during three
      visual occlusion conditions: (i) full visibility, (ii) occlusion at T-1 step (T:
      time of obstacle crossing), and (iii) occlusion at T-2 steps. Toe clearances of
      both the lead and trail limb (LTC and TTC) were calculated. LTC in the occlusion
      at T-2 steps condition was significantly greater than that in other conditions.
      Furthermore, a significant correlation was observed between LTC and TTC in both
      groups, regardless of the condition or obstacle height. In the older adult group
      alone, step width in the occlusion at T-2 steps condition increased relative to
      that in full visibility conditions. The results of the present study suggest that
      there is no difference in the characteristics of visuomotor control for
      appropriate obstacle crossing based on age. However, older adults may exhibit
      increased dependence on visual information for postural stability; they may also
      need an increased step width when lacking information regarding their positional
      relationship to obstacles.

PMID- 28437761
TI  - Negative appraisals and fear extinction are independently related to PTSD
      symptoms.
AB  - BACKGROUND: Considerable research has revealed impaired fear extinction to be a
      significant predictor of PTSD. Fear extinction is also considered the primary
      mechanism of exposure therapy, and a critical factor in PTSD recovery. The
      cognitive theory of PTSD proposes that symptoms persist due to excessive negative
      appraisals about the trauma and its sequelae. Research has not yet examined the
      relationship between fear extinction and negative appraisals in PTSD. METHODS: A
      cross-sectional sample of participants with PTSD (n =21), and trauma-exposed
      controls (n =33) underwent a standardized differential fear conditioning and
      extinction paradigm, with skin conductance response (SCR) amplitude serving as
      the index of conditioned responses. The Posttraumatic Cognitions Inventory (PTCI)
      was used to index catastrophic negative appraisals. RESULTS: Participants with
      PTSD demonstrated a slower decrease in overall SCR responses during extinction
      and greater negative appraisals compared to the group. A moderation analysis
      revealed that both negative trauma-relevant appraisals and fear extinction
      learning were independently associated with PTSD symptoms, but there was no
      moderation interaction. LIMITATIONS: The current study was limited by a modest
      sample size, leading to the inclusion of participants with subclinical PTSD
      symptoms. Further, the current study only assessed fear extinction learning;
      including a second day extinction recall task may show alternative effects.
      CONCLUSIONS: These findings indicate that negative appraisals and fear extinction
      did not interact, but had independent relationships with PTSD symptoms. Here we
      show for the first time in an experimental framework that negative appraisals and
      fear extinction play separate roles in PTSD symptoms.

PMID- 28437762
TI  - Public attitudes toward depression and help-seeking: Impact of the OSPI-Europe
      depression awareness campaign in four European regions.
AB  - BACKGROUND: Public attitudes toward depression and help-seeking behaviour are
      important factors influencing depressed people to obtain professional help and
      adequate treatment. OSPI-Europe is a multi-level suicide prevention programme
      including a public awareness campaign. It was implemented in four regions of four
      European countries (Germany, Hungary, Ireland and Portugal). This paper reports
      the results of the evaluation of the campaign, including its visibility and
      effects of the campaign on stigma associated with depression and help-seeking
      behaviour. METHODS: A representative general population survey (N=4004) including
      measures on personal stigma, perceived stigma, openness to help, perceived value
      of help, and socio-demographic variables was conducted in the four intervention
      and four control regions in a cross-sectional pre-post design. RESULTS: The
      public awareness campaign was considerably more visible in Germany and Portugal
      compared to Ireland and Hungary. Visibility was further affected by age and years
      of schooling. Personal stigma, perceived stigma and openness toward professional
      help varied significantly across the four countries. Respondents in the
      intervention regions showed significantly less personal depression stigma than
      respondents in the control regions after the campaign. Respondents of the
      intervention region who were aware of the campaign reported more openness toward
      seeking professional help than respondents who were unaware of it. CONCLUSION:
      The OSPI-Europe awareness campaign was visible and produced some positive
      results. At the same time, it proved to be difficult to show strong, measurable
      and unambiguous effects, which is in line with previous studies. Public awareness
      campaigns as conducted within OSPI-Europe can contribute to improved attitudes
      and knowledge about depression in the general public and produce synergistic
      effects, in particular when the dissemination of awareness campaign materials is
      simultaneously reinforced by other intervention levels of a multi-level
      intervention programme. LIMITATIONS: The survey was cross-sectional and based on
      self-report, so no causal inferences could be drawn.

PMID- 28437764
TI  - The use of lithium for the treatment of bipolar disorder: Recommendations from
      clinical practice guidelines.
AB  - BACKGROUND: Lithium is an effective mood stabilizer that is used principally for
      the management of bipolar disorder (BD). Its administration is complex and often
      requires sophisticated management and assiduous monitoring. When considering the
      use of lithium therapy for bipolar disorder, clinicians are advised to refer to
      recommendations outlined in clinical practice guidelines (CPGs); but because of
      varying emphases placed by different international CPGs, recommendations
      addressing the practical use of lithium lack consistency. METHOD: In order to
      inform clinicians of optimal lithium therapy for bipolar disorder, we compared
      and synthesized recommendations for the treatment of bipolar disorder made by
      recognized CPGs internationally. We conducted a search of the literature and
      extracted guidance across multiple clinical issues, including clinical
      indications, disorder subtypes, additional uses, special populations, practical
      aspects, and side effects. RESULTS: Collectively, CPGs consider lithium most
      robustly as a first-line intervention for maintenance treatment of bipolar
      disorder and strongly for the treatment of mania, with relatively modest support
      for the management of acute bipolar depression. Additionally, there is consensus
      across the CPGs that lithium tangibly reduces the risk of suicide. Generally,
      CPGs provide guidance on the many facets of initiating and maintaining patients
      on lithium therapy, but individually the CPGs varied in terms of depth and
      practical guidance they provide across these areas. However, consensus was
      established across many key areas of practice such as the ideal lithium plasma
      concentration for maintenance and monitoring (0.6-0.8mmol/L), along with the need
      for regular monitoring of renal and endocrine function. However, with more
      complex aspects (e.g., atypical presentations) and in special populations (e.g.,
      youth; pregnancy and post-partum; older adults), guidance varied considerably and
      clear consensus recommendations were more difficult to achieve. In younger adults
      desirable plasma lithium levels of 0.6-0.8mmol/L can perhaps be achieved with
      comparatively lower doses and in the very elderly it may be prudent to target
      lower plasma levels in the first instance. These are important practical points
      for consideration that, along with many others offered throughout the article,
      should assist clinicians in dissecting the more complex aspects of management
      with greater precision. LIMITATIONS: This review was limited to CPGs written in
      English. CPGs are themselves limited by reliance on evidence that often has
      little resemblance to real-world presentations. An important area that is not
      sufficiently addressed in the CPGs is clear guidance on the cessation of lithium
      therapy. CONCLUSIONS: Further research is needed on many aspects of lithium
      therapy and this alongside existing knowledge needs to be used more consistently
      to inform CPGs, which should also incorporate empirical evidence and clinical
      experience. The recommendations in this paper provide a useful synthesis of
      guidance available currently.

PMID- 28437763
TI  - Depression and insomnia as mediators of the relationship between distress and
      quality of life in cancer patients.
AB  - BACKGROUND: Distress in cancer patients leads to poorer quality of life (QOL) and
      negatively impacts survival. For efficient management of a patient's disease
      course, the interrelationships among distress, depression, insomnia, and QOL must
      be understood. This study aimed to investigate whether depression and insomnia
      mediate the relationship between distress and QOL in cancer patients. METHODS:
      Cancer patients referred to a specialized psycho-oncology clinic (n=208)
      participated in this study. Distress, depression, insomnia, and QOL were measured
      with the following questionnaires: Distress Thermometer, Hospital Anxiety and
      Depression Scale, Insomnia Severity Index, and Functional Assessment of Cancer
      Therapy-General. Structural equation modeling and path analysis were performed to
      analyze the mediating effects of depression and insomnia on the relationship
      between distress and QOL. RESULTS: Distress exerted nearly equal direct (beta=
      0.291, p=0.002) and indirect (mediated by depression and insomnia) (beta=-0.299,
      p=0.003) negative effects on QOL. Depression exhibited the largest direct
      negative effect on QOL. The indirect effects of distress on QOL through
      depression alone, through insomnia alone, and through an insomnia to depression
      pathway were all significant (beta=-0.122, p=0.011; beta=-0.102, p=0.002; and
      beta=-0.075, p<0.001, respectively). LIMITATIONS: The cross-sectional analyses
      limit the measurement of causal relationships between each variable. CONCLUSIONS:
      Depression and insomnia, both individually and as part of an interrelated
      pathway, partially mediate the relationship between distress and QOL. Appropriate
      interventions to alleviate insomnia and depression may mitigate the negative
      impacts of distress on QOL in cancer patients.

PMID- 28437765
TI  - Suicidality associated with PTSD, depression, and disaster recovery status among
      adult survivors 8 years after the 2008 Wenchuan earthquake in China.
AB  - It has been eight years since the Wenchuan earthquake. We don't know how the
      lives of those affected by the disaster may remain blighted by its effects, or
      how many remain thus affected. The aim of the present study was to examine the
      relationship of disaster exposure, PTSD, depression and suicidal behaviors, using
      data from a cross-sectional survey conducted in earthquake-affected areas of
      China. 1369 participants were recruited from two different sites that were
      severely affected by the Wenchuan earthquake. The survey assessed suicidality
      (suicidal ideation, plans and attempts) and other mental health issues. Probable
      PTSD was assessed using the Impact of Event Scale-Revised (IES-R). The Center for
      Epidemiologic Studies Depression Scale (CES-D) Chinese edition was used to assess
      depressive symptoms. The results showed that 11.2% of participants felt that
      their lives had not yet recovered from the effects of the Wenchuan earthquake,
      even after eight years. Suicidal ideation, plans, and attempts were reported by
      9.1%, 2.9%, and 3.3%, respectively, of the respondents. PTSD, depression, and
      perceived non-recovery were highly associated with suicidality. These results
      indicate that suicidality can be a long-term mental health sequela of disaster.
      Targeted, long-term suicide prevention programs for adult survivors should be
      further developed.

PMID- 28437766
TI  - Cyanobacterial lectins characteristics and their role as antiviral agents.
AB  - Lectins are ubiquitous proteins/glycoproteins of non-immune origin that bind
      reversibly to carbohydrates in non-covalent and highly specific manner. These
      lectin-glycan interactions could be exploited for establishment of novel
      therapeutics, targeting the adherence stage of viruses and thus helpful in
      eliminating wide spread viral infections. Here the review focuses on the
      haemagglutination activity, carbohydrate specificity and characteristics of
      cyanobacterial lectins. Cyanobacterial lectins exhibiting high specificity
      towards mannose or complex glycans have potential role as anti-viral agents.
      Prospective role of cyanobacterial lectins in targeting various diseases of
      worldwide concern such as HIV, hepatitis, herpes, influenza and ebola viruses has
      been discussed extensively. The review also lays emphasis on recent studies
      involving structural analysis of glycan-lectin interactions which in turn
      influence their mechanism of action. Altogether, the promising approach of these
      cyanobacterial lectins provides insight into their use as antiviral agents.

PMID- 28437767
TI  - Building-integrated agriculture: A first assessment of aerobiological air quality
      in rooftop greenhouses (i-RTGs).
AB  - Building-integrated rooftop greenhouse (i-RTG) agriculture has intensified in
      recent years, due to the growing interest in the development of new agricultural
      spaces and in the promotion of food self-sufficiency in urban areas. This paper
      provides a first assessment of the indoor dynamics of bioaerosols in an i-RTG,
      with the aim of evaluating biological air quality in a tomato greenhouse near
      Barcelona. It evaluates the greenhouse workers' exposure to airborne pollen and
      fungal spores in order to prevent allergy problems associated with occupational
      tasks. Moreover, it evaluates whether the quality of the hot air accumulated in
      the i-RTG is adequate for recirculation to heat the building. Daily airborne
      pollen and fungal spore concentrations were measured simultaneously in the indoor
      and outdoor environments during the warm season. A total of 4,924pollengrains/m3
      were observed in the i-RTG, with a peak of 334pollengrains/m3day, and a total of
      295,038 fungal spores were observed, reaching a maximum concentration of
      26,185spores/m3day. In general, the results showed that the most important source
      of pollen grains and fungal spores observed indoors was the outdoor environment.
      However, Solanaceae pollen and several fungal spore taxa, such as the allergenic
      Aspergillus/Penicillium, largely originated inside the greenhouses or were able
      to colonize the indoor environment under favourable growing conditions. Specific
      meteorological conditions and agricultural management tasks are related to the
      highest observed indoor concentrations of pollen grains and fungal spores.
      Therefore, preventive measures have been suggested in order to reduce or control
      the levels of bioaerosols indoors (to install a system to interrupt the
      recirculation of air to the building during critical periods or to implement
      appropriate air filters in ventilation air ducts). This first evaluation could
      help in making decisions to prevent the development of fungal diseases,
      specifically those due to Oidium and Torula.

PMID- 28437768
TI  - Glomeromycota communities survive extreme levels of metal toxicity in an orphan
      mining site.
AB  - Abandoned tailing basins and waste heaps of orphan mining sites are of great
      concern since extreme metal contamination makes soil improper for any human
      activity and is a permanent threat for nearby surroundings. Although spontaneous
      revegetation can occur, the process is slow or unsuccessful and
      rhizostabilisation strategies to reduce dispersal of contaminated dust represent
      an option to rehabilitate such sites. This requires selection of plants tolerant
      to such conditions, and optimization of their fitness and growth. Arbuscular
      mycorrhizal fungi (AMF) can enhance metal tolerance in moderately polluted soils,
      but their ability to survive extreme levels of metal contamination has not been
      reported. This question was addressed in the tailing basin and nearby waste heaps
      of an orphan mining site in southern France, reaching in the tailing basin
      exceptionally high contents of zinc (ppm: 97,333 total) and lead (ppm: 31,333
      total). In order to contribute to a better understanding of AMF ecology under
      severe abiotic stress and to identify AMF associated with plants growing under
      such conditions, that may be considered in future revegetation and
      rhizostabilisation of highly polluted areas, nine plant species were sampled at
      different growing seasons and AMF root colonization was determined. Glomeromycota
      diversity was monitored in mycorrhizal roots by sequencing of the ribosomal LSU.
      This first survey of AMF in such highly contaminated soils revealed the presence
      of several AMF ribotypes, belonging mainly to the Glomerales, with some examples
      from the Paraglomerales and Diversisporales. AMF diversity and root colonization
      in the tailing basin were lower than in the less-contaminated waste heaps. A
      Paraglomus species previously identified in a polish mining site was common in
      roots of different plants. Presence of active AMF in such an environment is an
      outstanding finding, which should be clearly considered for the design of
      efficient rhizostabilisation processes.

PMID- 28437769
TI  - Contamination study of forest track soils located in a recreational area and
      filled with steel industry waste 30years ago.
AB  - The reuse of waste is increasingly widespread in order to avoid the exploitation
      of natural resources and to reduce costs. An example of that reuse is the
      employment of steel slag, a by-product from the steel making process. When the
      steel is produced through an electric arc furnace (EAF), two types of slag are
      generated: black and white slag. One application rarely used for this waste is as
      filler in forest tracks. In this work, two forest tracks of the Basque Country
      (northern Spain) filled with black and white slag 19 and 35years ago,
      respectively, have been studied. Leaching tests were performed using Milli-Q
      water and acetic acid over the slags collected in that area. Additionally, soil
      samples collected near the slags were subjected to acid digestion. In these soil
      samples, there were elements of natural origin and others that could come from
      the leaching of the slag. Some of the more leached elements from the black slag
      (Ca, Fe, K, Cr, Se, W, Mn and Mo) and white slag (Mg, Al, Na, Co, Ni and Cu)
      coincided with the elements of highest concentration found in the soil samples.
      Moreover, there were differences in some elemental concentrations of soil samples
      with only black slag (higher presence of Ca and Mg) and soil samples with a
      mixture of both types of slag. It was noticeable that the highest concentration
      values of the measured elements were found on a specific side of the forest
      tracks, possibly due to the runoff water or the higher inclination of that side.
      On the other hand, some areas of both forest tracks could be considered
      contaminated by Cr according to a standard values from the Basque regulation,
      posing a risk to human health since they are recreational areas.

PMID- 28437770
TI  - Historical and contemporary metal budgets for a boreal shield lake.
AB  - Metal concentrations in sediment cores are widely used to reconstruct metal
      deposition histories, but rarely have metal budgets based on measured inputs
      (atmospheric deposition and inflows) and lake outflows been compared with metal
      fluxes estimated from lake sediment cores. In this study, budgets for six metals
      (As, Cd, Co, Cu, Ni and Pb) were estimated by measuring inputs in bulk
      deposition, inputs in the major inflow and export in the lake outflow for one
      hydrologic year (2002-2003) at Plastic Lake, Ontario, Canada. Inputs in bulk
      deposition were between 0.03mgm-2y-1 (Co) and 0.69mgm-2y-1 (Cu), which
      represented between 2.5 and 80.7% of total metal inputs to the lake. The
      estimated budgets for Co, Cd and Ni, which exhibit similar geochemical behavior
      in the major inflow, were comparable to budgets estimated from the upper section
      of a sediment core taken in 2002, taking into account previously published
      correction factors for sediment focusing. For example, mass budgets for Co, Cd
      and Ni were 1.24, 0.28 and 1.89mgm-2y-1, compared with sediment budgets estimated
      to be 0.90, 0.19 and 4.72mgm-2y-1, respectively. In contrast, measured budgets
      for As, Cu and Pb, which also behave similarly in inflows (and different to Co,
      Cd and Ni), were between 3 (As) and 40 times lower than estimates from the upper
      sediment core. A possible explanation for the discrepancy is that sediment
      focusing transfers sediment from shallow to deep areas, which for metals like Pb,
      which have strong affinities for organic matter and where atmospheric deposition
      has decreased 15 fold since 1978 (4.31mgm-2y-1 in 1978 to 0.28mgm-2y-1 in 2013),
      leads to the transfer and accumulation of pollution metals to deeper parts of the
      lake long after a decrease in atmospheric deposition.

PMID- 28437771
TI  - Solvent bar micro-extraction (SBME) based determination of PAHs in seawater
      samples.
AB  - Measuring the impact of PAHs in seawater samples is often difficult due to the
      low concentrations in which they appear and the complexity of the sample matrix.
      Traditional methods for sample preparation such as liquid-liquid extraction and
      solid phase extraction require the use of excessive amounts of solvents and
      reagents, and sample handling. In this work, hollow fiber liquid phase micro
      extraction (HFLPME), in the configuration of solvent bar micro-extraction (SBME),
      was proposed as an environmentally friendly and more effective tool, for the
      extraction of the 16 priority PAHs from seawater samples. Extraction was
      conducted using hexane as a solvent. Enrichment factors from 45 to 163 were
      obtained after 60min at a stirring rate of 500rpm in the sample. Moreover, a
      negative linear relationship was observed between the enrichment factor and the
      molecular weight of the PAHs. Under optimized conditions, the limits of detection
      were in the range from 0.21 to 0.82ngL-1, the method showed a linear response up
      to 500MUgL-1, and the average relative standard deviation for seawater samples
      spiked with 5ngL-1 was 11.6%. After calibration, the SBME was applied to extract
      PAHs in seawater samples from the Bay of Cadiz (SW Spain), showing an average
      recovery of 99%. In conclusion, the SBME is an environmentally friendly, one-step
      alternative for sample preparation in the determination of PAHs in seawater
      samples.

PMID- 28437772
TI  - Shifts in soil microbial metabolic activities and community structures along a
      salinity gradient of irrigation water in a typical arid region of China.
AB  - Saline water irrigation can change soil environment, which thereby influence soil
      microbial process. Based on a field experiment, the shifts in soil microbial
      metabolic activities and community structures under five irrigation salinities
      were studied using Biolog and metagenomic methods in this study. The results
      demonstrated that microbial metabolic activities were greatly restrained in
      saline water irrigated soils, as average well color development (AWCD) reduced
      under all saline water irrigation treatments. Although no significant difference
      in carbon substrate utilization of all six categories was observed among Mild,
      Medium, High and Severe treatments, the consumption of sole carbon source was
      significantly varied. Especially, asparagine, galacturonic, putrescine and 4
      benzoic acid played a decisive role in dominating the differences. Soil bacterial
      richness and diversity increased with irrigation salinity while the number of
      bacterial phyla decreased. Three significantly increased (Proteobacteria,
      Actinobacteria and Chloroflexi), two decreased (Planctomycetes, Bacteroidetes)
      and two irresponsive (Gemmatimonadetes and Acidobacteria) phyla were observed as
      the dominant groups in saline water irrigated soils. The results presented here
      could improve the understanding of the soil biological process under saline
      circumstance.

PMID- 28437773
TI  - Are hospital emergency department visits due to dog bites associated with ambient
      temperature? A time-series study in Beijing, China.
AB  - BACKGROUND: It is well documented that suboptimal ambient temperature is
      associated with cardiovascular and respiratory diseases. However, no study has
      examined the relation between temperature and dog bites. OBJECTIVES: To study the
      association between ambient temperature and daily hospital emergency department
      visits due to dog bites (EDVDBs) in Beijing, China; and to explore whether the
      temperature-EDVDB association varies by sex and age. METHODS: Daily EDVDBs were
      collected from a hospital appointed for dog bites in Beijing during 2012-2014. A
      quasi-Poisson regression with distributed lag non-linear model (DLNM) was
      employed to estimate the impact of temperature on daily EDVDBs. Stratified
      analysis was performed to examine the temperature-EDVDB association by sex and
      age-groups. Sensitivity analysis was performed to check the robustness of the
      results by adjusting other meteorological variables and air pollutants. RESULTS:
      A total of 42,481 EDVDBs were collected, with daily cases ranged from 15 to 71.
      The association between temperature and EDVDBs was U-shaped, with extreme cold
      temperature showing a weaker, delayed and shorter effect on the risk of dog bites
      while the effect of extreme hot temperature being stronger, more immediate and
      lasting longer. Cold temperature had a greater impact on female whereas male was
      more sensitive to hot temperature. The temperature-EDVDB association was
      unapparent in the 15-21years group. The cold effect was only significant in the 0
      14years group whereas all age-groups suffered from the similar heat effect except
      those aged 22-45years. Adjusting other meteorological variables and air
      pollutants did not change the results. CONCLUSIONS: The impact of temperature on
      EDVDBs is U-shaped in Beijing, China which varies by sex and age. The temperature
      effect is independent from other meteorological variables and air pollutants.

PMID- 28437774
TI  - Bacterial community dynamics and functional variation during the long-term
      decomposition of cyanobacterial blooms in-vitro.
AB  - Cyanobacterial blooms drastically influence carbon and nutrient cycling in
      eutrophic freshwater lakes. To understand the mineralization process of
      cyanobacteria-derived particulate organic matter (CyanPOM), the aerobic
      degradation of cyanobacterial blooms dominated by Microcystis sp. was
      investigated over a 95-day microcosm experiment. Approximately 91%, 95% and 83%
      of the initial particulate organic carbon (POC), particulate organic nitrogen
      (PON), and particulate organic phosphorus (POP) were decomposed, respectively.
      The POC:PON ratio gradually increased from 5.9 to 13.5, whereas the POC:POP ratio
      gradually decreased from 230.3 to 120. These results indicated that the coupling
      of POC, PON, and POP changed during the decomposition of CyanPOM. Moreover,
      approximately 29%, 51% and 46% of POC, PON, and POP were mineralized to dissolved
      organic carbon, NO3-, and PO43-, respectively. Rhodospirillales (10.9%),
      Burkholderiales (16.5%), and Verrucomicrobiales (14.3%) dominated during the
      rapid phase (days 0-21), whereas Sphingomonadales (12.8%), Rhizobiales (11.8%),
      and Xanthomonadales (36.5%) dominated during the slow phase (days 21-50) of
      CyanPOM decomposition. Nitrospira (16.6%-32.9%) dominated and NO3- increased
      during the refractory phase (days 50-95), thus suggesting the occurrence of
      nitrification. Redundancy analysis revealed that bacterial communities during
      rapid decomposition were distinct from those during the slow and refractory
      periods. POC:POP, NH4+, and NO3- were the major driving factors for the patterns
      of bacterial communities. Furthermore, increase in nitrogen metabolism, methane
      metabolism, amino acid related enzymes and pyruvate metabolism characterized the
      functional variation of bacterial communities during degradation. Therefore,
      CyanPOM is an important nutrient source, and its decomposition level shapes
      bacterial communities.

PMID- 28437775
TI  - Effect of nitrification inhibitors on mitigating N2O and NO emissions from an
      agricultural field under drip fertigation in the North China Plain.
AB  - N2O and NO emissions from a winter wheat-summer maize rotation field with five
      different treatments in the North China Plain (NCP) were comparably investigated
      from 8 October 2014 to 11 October 2015. Compared with the treatments with only
      flood or drip irrigation, evident emission peaks of N2O and NO from the
      fertilization treatments with flood irrigation (A-Flood) and with drip
      fertigation (A-Drip) were observed after each fertilization event, whereas their
      emissions from the fertilization treatments with nitrification inhibitors under
      drip fertigation (A+DCD-Drip and A+Nitrapyrin-Drip) were greatly suppressed. The
      reduction effect of the nitrification inhibitors on N2O and NO emissions was
      found to be more conspicuous during the maize season than during the wheat
      season, implying that the soil temperature could play an important role in the
      reduction effect. Compared with the A-Flood treatment, the annual cumulative
      emission from the A-Drip treatment reduced by 22% for N2O and increased by 18%
      for NO, whereas the reductions of N2O and NO from the treatments with
      nitrification inhibitors could achieve as high as 66% and 95%, respectively. The
      yields of the maize were significantly greater from the A-Drip and A+Nitrapyrin
      Drip treatments than from the A-Flood treatment, and the yields of the wheat were
      almost same among the treatments of A-Flood, A-Drip and A+DCD-Drip. Considering
      the yields, the water saving and the reduction of N2O and NO emissions, the
      application of nitrification inhibitor combined with drip fertigation is
      recommended in the NCP.

PMID- 28437776
TI  - Large-scale seaweed cultivation diverges water and sediment microbial communities
      in the coast of Nan'ao Island, South China Sea.
AB  - Seaweed cultivation not only provides economy benefits, but also remediates the
      environment contaminated by mariculture of animals (e.g., fish, shrimps).
      However, the response of microbial communities to seaweed cultivation is poorly
      understood. In this study, we analyzed the diversity, composition, and structure
      of water and sediment microbial communities at a seaweed, Gracilaria
      lemaneiformis, cultivation zone and a control zone near Nan'ao Island, South
      China Sea by MiSeq sequencing of 16S rRNA gene amplicons. We found that large
      scale cultivation of G. lemaneiformis increased dissolved oxygen (DO) and pH but
      decreased inorganic nutrients, possibly due to nutrient uptake, photosynthesis
      and other physiological processes of G. lemaneiformis. These environmental
      changes significantly (adonis, P<0.05) shifted the microbial community
      composition and structure of both water column and sediment samples in the G.
      lemaneiformis cultivation zone, compared to the control zone. Also, certain
      microbial taxa associated with seaweed, such as Arenibacter, Croceitalea,
      Glaciecola, Leucothrix and Maribacter were enriched at the cultivation zone. In
      addition, we have proposed a conceptual model to summarize the results in this
      study and guide future studies on relationships among seaweed processes,
      microbial communities and their environments. Thus, this study not only provides
      new insights into our understanding the effect of G. lemaneiformis cultivation on
      microbial communities, but also guides future studies on coastal ecosystems.

PMID- 28437777
TI  - Testing decontaminated sediments as a substrate for ornamentals in field nursery
      plantations.
AB  - When canals and harbours are dredged, huge amount of polluted sediments has to be
      stocked and transported to the landfill with incredibly high costs of management.
      Among the remediation techniques for the reclamation of polluted sediments and
      soils, phytoremediation represents a sustainable and effective technique though
      still not fully promoted or commercialized. In this study we have tested the
      suitability for plant nursing of a substrate resulting from sediments dredged
      from a canal and treated with phytoremediation. The experiment was set up in
      2014. It aimed to test the physical, chemical and hydrological characteristics of
      two mixes of remediated sediments and agronomic soil (at 33% and 50% by volume)
      compared to control soil (100% agronomic soil), and to assess the growth of three
      ornamental species (Viburnum tinus L., Photinia x fraseri var. red robin,
      Eleagnus macrophylla Thunb.) together with the suitability for root balling. The
      mixed substrates produced good results in terms of water drainage, and were
      similar to the control in terms of soluble nutrients, guaranteeing and enhancing
      the aboveground and belowground growth of all the three species, especially V.
      tinus. In contrast, mixed substrates impaired root ball compaction with root ball
      breakage observed especially in 50% sediment/soil mix. Therefore, the use of
      remediated sediments in plant nursery can be limited to specific productions or
      practices.

PMID- 28437778
TI  - Strengthening governance for intertidal ecosystems requires a consistent
      definition of boundaries between land and sea.
AB  - The protection of intertidal ecosystems is complex because they straddle both
      marine and terrestrial realms. This leads to inconsistent characterisation as
      marine and/or terrestrial systems, or neither. Vegetated intertidal ecosystems
      are especially complex to classify because they can have an unclear border with
      terrestrial vegetation, causing confusion around taxonomy (e.g., mangrove-like
      plants). This confusion and inconsistency in classification can impact these
      systems through poor governance and incomplete protection. Using Australian
      mangrove ecosystems as a case study, we explore the complexity of how land and
      sea boundaries are defined among jurisdictions and different types of
      legislation, and how these correspond to ecosystem boundaries. We demonstrate
      that capturing vegetated intertidal ecosystems under native vegetation laws and
      prioritizing the mitigation of threats with a terrestrial origin offers the
      greatest protection to these systems. We also show the impact of inconsistent
      boundaries on the inclusion of intertidal ecosystems within protected areas. The
      evidence presented here highlights problems within the Australian context, but
      most of these issues are also challenges for the management of intertidal
      ecosystems around the world. Our study demonstrates the urgent need for a global
      review of legislation governing the boundaries of land and sea to determine
      whether the suggestions we offer may provide global solutions to ensuring these
      critical systems do not fall through the cracks in ecosystem protection and
      management.

PMID- 28437779
TI  - Further evidence of male offspring preference for certain subgroups in the United
      States (2007-2015).
AB  - INTRODUCTION: Males are born in excess of females. This ratio (M/T=male/total
      births) is influenced by various factors. A recent study showed that M/T in the
      United States (US) is Asian or Pacific Islander>White>American Indian or Alaska
      Native>Black or African American. This study was carried out in order to
      ascertain whether there are M/T differences in different races in the US by birth
      order. METHODS: Monthly male and female live births by race and birth order for
      the entire US were obtained for 2007-2015 with birth order as 1->=6 for these
      races. RESULTS: There were 36,499,163 births. M/T decreased with increasing
      sibling order for all races (p<0.0001) except for Asian or Pacific Islander
      births where M/T rose progressively to 3rd order births (p<0.0001) then fell
      (p=0.0002). Weighted mean maternal age for each birth order by race order was
      Asian or Pacific Islander>White Black or African American/American Indian or
      Alaska Native. The differences between adjacent means were all significant
      (almost all p<0.0001). The mean maternal age spread followed the same order.
      DISCUSSION: Asians favour male offspring. This group may be systematically
      implementing foetal sex-specific feticide and/or implementing a Type1 stopping
      rule when a male birth is achieved in order to maximise male births. The
      potential putative effect of increasing maternal age to decrease M/T is not only
      excluded in this race, but goes contrary to the findings of this study insofar as
      Asian or Pacific Islander births have the oldest mean maternal ages. Son
      preference strongly persists in the US.

PMID- 28437780
TI  - Evidence-based practice knowledge, attitudes, and practice of online graduate
      nursing students.
AB  - OBJECTIVES: This study aimed to evaluate changes in evidence-based practice (EBP)
      knowledge, attitudes, and practice of nursing students before and after
      completing an online, graduate level, introductory research/EBP course. DESIGN: A
      prospective one-group pretest-posttest design. SETTINGS: A private university in
      the Midwestern, USA. PARTICIPANTS: Sixty-three online nurse practitioner students
      in Master's program. METHODS: A convenient sample of online graduate nursing
      students who enrolled in the research/EBP course was invited to participate in
      the study. Study outcomes were measured using the Evidence-Based Practice
      Questionnaire (EBPQ) before and after completing the course. Descriptive
      statistics and paired-Samples t-test was used to assess the mean differences
      between pre-and post-test scores. RESULTS: Overall, students' post-test EBP
      scores were significantly improved over pre-test scores, t(63)=-9.034, p<0.001).
      Statistically significant differences were found for practice of EBP mean scores
      t(63)=-12.78, p=0.001). No significant differences were found between pre and
      post-tests on knowledge and attitudes toward EBP scores. Most frequently cited
      barriers to EBP were lack of understanding of statistics, interpretation of
      findings, lack of time, and lack of library resources.

PMID- 28437781
TI  - The reliability and criterion validity of 2D video assessment of single leg squat
      and hop landing.
AB  - The objective was to assess the intra-tester, within and between day reliability
      of measurement of hip adduction (HADD) and frontal plane projection angles (FPPA)
      during single leg squat (SLS) and single leg landing (SLL) using 2D video and the
      validity of these measurements against those found during 3D motion capture. 15
      healthy subjects had their SLS and SLL assessed using 3D motion capture and video
      analysis. Inter-tester reliability for both SLS and SLL when measuring FPPA and
      HADD show excellent correlations (ICC2,1 0.97-0.99). Within and between day
      assessment of SLS and SLL showed good to excellent correlations for both
      variables (ICC3,1 0.72-91). 2D FPPA measures were found to have good correlation
      with knee abduction angle in 3-D (r=0.79, p=0.008) during SLS, and also to knee
      abduction moment (r=0.65, p=0.009). 2D HADD showed very good correlation with 3D
      HADD during SLS (r=0.81, p=0.001), and a good correlation during SLL (r=0.62,
      p=0.013). All other associations were weak (r<0.4). This study suggests that 2D
      video kinematics have a reasonable association to what is being measured with 3D
      motion capture.

PMID- 28437782
TI  - Detection of Renal Hypoxia in Lupus Nephritis Using Blood Oxygen Level-Dependent
      MR Imaging: A Multiple Correspondence Analysis.
AB  - BACKGROUND/AIMS: Nephrologists have pursued ideal, dynamic and noninvasive
      methods for assessing renal function and disease progression. Blood oxygen level
      dependent (BOLD) imaging is a useful technique for assessing renal disease. This
      current study was performed to explore the correlation between the hypoxia
      iconographical index and renal pathological features in lupus nephritis. METHODS:
      Adult patients with lupus nephritis (LN) and healthy volunteers were recruited
      for this study. Renal biopsy tissues were characterized based on the LNISN/RPS
      2003 classification. R2* values of functional magnetic resonance parameters were
      acquired using the BOLD technique. The data characteristics of R2* values of
      different pathological patterns were calculated. Multiple correspondence analysis
      (MCA) was performed to explore the correlation between R2* values and clinical or
      pathological features. RESULTS: A total of twenty-three patients and eighteen
      healthy volunteers were examined with BOLD MRI. Renal pathological patterns
      included five class III (including 3 class III+V), eight class IV (including 4
      class IV+V) and five class IV. The mean renal R2* values in LN patients were
      higher than those in healthy volunteers. R2* values in class V patients were
      higher than those in class IV and class III. The MCA showed that higher R2*
      values were associated with pathological features in class V patients.
      CONCLUSIONS: The extent of renal hypoxia in patients with LN was more serious
      compared with the healthy volunteers. Differentiated mechanisms of renal
      oxygenation are possibly involved in proliferative and non-proliferative LN
      patients. R2* values may be linked with multiple clinical and pathological
      indexes.

PMID- 28437783
TI  - Evacuation of a Tertiary Neonatal Centre: Lessons from the 2016 Kumamoto
      Earthquakes.
AB  - BACKGROUND: Newborn infants hospitalised in the neonatal intensive care unit
      (NICU) are vulnerable to natural disasters. However, publications on evacuation
      from NICUs are sparse. The 2016 Kumamoto Earthquakes caused serious damage to
      Kumamoto City Hospital and its level III regional core NICU. Local/neighbour NICU
      teams and the disaster-communication team of a neonatal academic society
      cooperated to evacuate 38 newborn infants from the ward. OBJECTIVE: The aim of
      this paper was to highlight potential key factors to improve emergency NICU
      evacuation and coordination of hospital transportation following natural
      disasters. METHODS: Background variables including clinical risk scores and
      timing/destination of transportation were compared between infants, who
      subsequently were transferred to destinations outside of Kumamoto Prefecture, and
      their peers. RESULTS: All but 1 of the infants were successfully evacuated from
      their NICU within 8 h. One very-low-birth-weight infant developed moderate
      hypothermia following transportation. Fourteen infants were transferred to NICUs
      outside of Kumamoto Prefecture, which was associated with the diagnosis of
      congenital heart disease, dependence on respiratory support, higher risk scores,
      and longer elapsed time from the decision to departure. There was difficulty in
      arranging helicopter transportation because the coordination office of the
      Disaster Medical Assistance Team had requisitioned most air/ground ambulances and
      only helped arrange ground transportations for 13 low-risk infants.
      Transportation for all 10 high-risk infants (risk scores greater than or equal to
      the upper quartile) was arranged by local/neighbour NICUs. CONCLUSIONS: Although
      the overall evacuation process was satisfactory, potential risks of relying on
      the adult-based emergency transportation system were highlighted. A better system
      needs to be developed urgently to put appropriate priority on vulnerable infants.

PMID- 28437784
TI  - The Physiology of Childhood Growth: Hormonal Regulation.
AB  - The growth patterns of a child changes from uterine life until the end of
      puberty. Height velocity is highest in utero and declines after birth until
      puberty when it rises again. Important hormonal regulators of childhood growth
      are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid
      hormone. This review gives an overview of these hormonal regulators of growth and
      their interplay with nutrition and other key players such as inflammatory
      cytokines.

PMID- 28437785
TI  - The Retina of Asian and African Elephants: Comparison of Newborn and Adult.
AB  - Elephants are precocial mammals that are relatively mature as newborns and mobile
      shortly after birth. To determine whether the retina of newborn elephants is
      capable of supporting the mobility of elephant calves, we compared the retinal
      structures of 2 newborn elephants (1 African and 1 Asian) and 2 adult animals of
      both species by immunohistochemical and morphometric methods. For the first time,
      we present here a comprehensive qualitative and quantitative characterization of
      the cellular composition of the newborn and the adult retinas of 2 elephant
      species. We found that the retina of elephants is relatively mature at birth. All
      retinal layers were well discernible, and various retinal cell types were
      detected in the newborns, including Muller glial cells (expressing glutamine
      synthetase and cellular retinal binding protein; CRALBP), cone photoreceptors
      (expressing S-opsin or M/L-opsin), protein kinase Calpha-expressing bipolar
      cells, tyrosine hydroxylase-, choline acetyltransferase (ChAT)-, calbindin-, and
      calretinin-expressing amacrine cells, and calbindin-expressing horizontal cells.
      The retina of newborn elephants contains discrete horizontal cells which
      coexpress ChAT, calbindin, and calretinin. While the overall structure of the
      retina is very similar between newborn and adult elephants, various parameters
      change after birth. The postnatal thickening of the retinal ganglion cell axons
      and the increase in ganglion cell soma size are explained by the increase in body
      size after birth, and the decreases in the densities of neuronal and glial cells
      are explained by the postnatal expansion of the retinal surface area. The
      expression of glutamine synthetase and CRALBP in the Muller cells of newborn
      elephants suggests that the cells are already capable of supporting the
      activities of photoreceptors and neurons. As a peculiarity, the elephant retina
      contains both normally located and displaced giant ganglion cells, with single
      cells reaching a diameter of more than 50 um in adults and therefore being almost
      in the range of giant retinal ganglion cells found in aquatic mammals. Some of
      these ganglion cells are displaced into the inner nuclear layer, a unique feature
      of terrestrial mammals. For the first time, we describe here the occurrence of
      many bistratified rod bipolar cells in the elephant retina. These bistratified
      bipolar cells may improve nocturnal contrast perception in elephants given their
      arrhythmic lifestyle.

PMID- 28437786
TI  - The Effect of Retraining on Treatment Success, Quality of Life, and Metabolic
      Parameters in Patients with Type 1 Diabetes Using an Insulin Pump.
AB  - OBJECTIVE: To investigate the effect of insulin pump user retraining on treatment
      success, quality of life, and metabolic parameters of patients with type 1
      diabetes using continuous subcutaneous insulin infusion. SUBJECTS AND METHODS: A
      total of 35 subjects participated in this prospective study. All patients were
      given insulin pump user retraining. Their knowledge level and application skills,
      metabolic parameters, quality of life, and satisfaction from treatment were
      evaluated at baseline and after 6 months. RESULTS: There was significant
      improvement in patients' knowledge and application skills after insulin pump user
      retraining (self-assessment of user skills: 69.7 +/- 11.5 vs. 76.3 +/- 11.3, p <
      0.001; knowledge level on technical issues: 3.3 +/- 1.1 vs. 4.1 +/- 1.8, p =
      0.003; glucose monitoring: 27.1 +/- 5.8 vs. 29.2 +/- 5.6, p = 0.006; management
      of hyperglycemia: 13.1 +/- 3.2 vs. 15.7 +/- 3.4, p < 0.001; management of pump
      and infusion site problems: 8.8 +/- 2.6 vs. 10.6 +/- 2.6, p = 0.001). Hemoglobin
      (Hb)A1c levels of patients with poor glycemic control improved after retraining
      (8.61% +/- 0.78 vs. 8.23% +/- 0.79, p = 0.02). However, no significant
      improvement in quality of life and treatment satisfaction parameters were found.
      CONCLUSION: Management of type 1 diabetes in insulin pump users can be
      significantly improved by retraining. Even a basic short-term retraining program
      helps patients to increase their knowledge level and ability to more effectively
      use the insulin pump. The fact that retraining significantly improves glycemic
      parameters in patients with poor metabolic control indicates that priority should
      be given to this group of patients. Further studies with individualized training
      programs in larger sample sizes with long-term follow-up are needed to establish
      the importance of retraining and create re-education plans for patients with type
      1 diabetes using an insulin pump.

PMID- 28437787
TI  - A Comparison of Three Different Volumes of Levobupivacaine for Caudal Block in
      Children Undergoing Orchidopexy and Inguinal Hernia Repair.
AB  - OBJECTIVE: The aim of this study was to compare the efficacy of 3 different
      volumes of 0.25% levobupivacaine caudally administered on the effect of intra-
      and postoperative analgesia in children undergoing orchidopexy and inguinal
      hernia repair. SUBJECTS AND METHODS: Forty children, aged 1-7 years, American
      Society of Anesthesiologists (ASA) physical status I and II, were randomized into
      3 different groups according to the applied volumes of 0.25% levobupivacaine:
      group 1 (n = 13): 0.6 mL?kg-1; group 2 (n = 10): 0.8 mL?kg-1; and group 3 (n =
      17): 1.0 mL?kg-1. The age, weight, duration of anesthesia, onset time of
      intraoperative analgesic, dosage, and addition of intraoperative fentanyl were
      compared among the groups. The time to first use of the analgesic and the number
      of patients who required analgesic 24 h after surgery in the time intervals
      within 6 h, between 6 and 12 h, and between 12 and 24 h postoperatively were
      evaluated among the groups. Statistical analyses were performed with a Dunnett t
      test, ANOVA, or Kruskal-Wallis test and chi2 test. Logistic regression analysis
      was used in order to examine predictive factors on duration of postoperative
      analgesia. RESULTS: Age, weight, duration of anesthesia, onset time of
      intraoperative analgesic, dosage, and addition of intraoperative fentanyl were
      similar among the groups. The time to first analgesic use did not differ among
      the groups, and logistic regression modelling showed that using the 3 different
      volumes of levobupivacaine had no predictive influence on duration of
      postoperative analgesia. The numbers of patients who required analgesics within 6
      h (3/2/3), between 6 and 12 h (3/1/3), and between 12 and 24 h (1/0/2) after
      surgery were similar among the groups. CONCLUSION: The 3 different volumes of
      0.25% levobupivacaine provided the same quality of intra- and postoperative pain
      relief in pediatric patients undergoing orchidopexy and inguinal hernia repair.

PMID- 28437788
TI  - High Prevalence of Polycystic Ovary Syndrome in Type 1 Diabetes Mellitus
      Adolescents: Is There a Difference Depending on the NIH and Rotterdam Criteria?
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is more frequently observed in type
      1 diabetes mellitus (T1DM) adult women than in nondiabetic women. No such
      prevalence has yet been studied in adolescent girls with T1DM. AIM: The aim of
      this study was to evaluate the prevalence of PCOS in adolescent girls with T1DM
      and to determine the clinical and hormonal features associated with the disorder.
      METHODS: A cross-sectional study of 53 adolescent girls (gynecological age >2
      years) referred for routine evaluation for T1DM was conducted. We diagnosed PCOS
      using the National Institutes of Health (NIH) and Rotterdam criteria. RESULTS:
      26.4 and 47.9% of adolescents had PCOS according to NIH (NIH-PCOS) and Rotterdam
      (Rotterdam-PCOS) criteria. 66.7% of NIH-PCOS adolescents had a complete phenotype
      associated with hyperandrogenism, oligomenorrhea, and polycystic ovarian
      morphology, unlike only 33.3% of the Rotterdam-PCOS adolescents. A family history
      of type 2 diabetes mellitus (T2DM) was more frequent in PCOS than in non-PCOS
      girls, whichever criteria were used. Late pubertal development and a T1DM
      diagnosis close to puberty were factors associated with NIH-PCOS. CONCLUSION:
      Adolescents with T1DM had a high prevalence of PCOS. More differences between
      PCOS and non-PCOS patients were found using the NIH criteria, suggesting that
      clinical characteristics might be more accurate for diagnosing PCOS in girls with
      T1DM. A family history of T2DM is associated with a high risk of PCOS.

PMID- 28437789
TI  - Comparative Proteomics Uncovers Correlated Signaling Network and Potential
      Biomarkers for Progression of Prostate Cancer.
AB  - BACKGROUND/AIMS: Prostate cancer is one of the most common cancers for males
      worldwide, and it is prone to show the metastatic foci in lymph node and bone
      with high mortality. To date, the potential mechanism and the corresponding
      biomarkers for metastatic prostate cancer are still lacking. Hence, our study
      aims to clarify the mechanism of prostate cancer progression and identify the
      useful biomarkers for metastatic prostate cancer. METHODS: The proteins and
      network tightly associated with tumor metastasis were identified using
      quantitative proteomics. Furthermore, the mRNA level of differential expressed
      proteins were confirmed using qRT-PCR, and the functional cluster analysis was
      performed using String and Cytoscape. RESULTS: Totally, our study identified 203
      differential proteins closely associated with tumor cell migration, and the mRNA
      expression of those proteins were verified by qPCR. Moreover, the migration
      associated molecular network was established using bioinformatics analysis.
      CONCLUSION: These data raveled the critical proteins for the cell migration of
      prostate cancer, and identified the potential markers for diagnosing the
      metastasis of prostate cancer.

PMID- 28437790
TI  - Utility in Treating Kidney Failure in End-Stage Liver Disease With Simultaneous
      Liver-Kidney Transplantation.
AB  - BACKGROUND: Simultaneous liver-kidney (SLK) transplantation plays an important
      role in treating kidney failure in patients with end-stage liver disease. It used
      5% of deceased donor kidney transplanted in 2015. We evaluated the utility,
      defined as posttransplant kidney allograft lifespan, of this practice. METHODS:
      Using data from the Scientific Registry of Transplant Recipients, we compared
      outcomes for all SLK transplants between January 1, 1995, and December 3, 2014,
      to their donor-matched kidney used in kidney-alone (Ki) or simultaneous pancreas
      kidney (SPK) transplants. Primary outcome was kidney allograft lifespan, defined
      as the time free from death or allograft failure. Secondary outcomes included
      death and death-censored allograft failure. We adjusted all analyses for donor,
      transplant, and recipient factors. RESULTS: The adjusted 10-year mean kidney
      allograft lifespan was higher in Ki/SPK compared with SLK transplants by 0.99
      years in the Model for End-stage Liver Disease era and 1.71 years in the pre
      Model for End-stage Liver Disease era. Death was higher in SLK recipients
      relative to Ki/SPK recipients: 10-year cumulative incidences 0.36 (95% confident
      interval 0.33-0.38) versus 0.19 (95% confident interval 0.17-0.21). CONCLUSIONS:
      SLK transplantation exemplifies the trade-off between the principles of utility
      and medical urgency. With each SLK transplantation, about 1 year of allograft
      lifespan is traded so that sicker patients, that is, SLK transplant recipients,
      are afforded access to the organ. These data provide a basis against which
      benefits derived from urgency-based allocation can be measured.

PMID- 28437791
TI  - Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver
      Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter
      Study: Erratum.

PMID- 28437793
TI  - Mindfulness-Based Stress Reduction for Treating Low Back Pain: A Systematic
      Review and Meta-analysis.
AB  - Background: Mindfulness-based stress reduction (MBSR) is frequently used to treat
      pain-related conditions, but its effects on low back pain are uncertain. Purpose:
      To assess the efficacy and safety of MBSR in patients with low back pain. Data
      Sources: Searches of MEDLINE/PubMed, Scopus, the Cochrane Library, and PsycINFO
      to 15 June 2016. Study Selection: Randomized controlled trials (RCTs) that
      compared MBSR with usual care or an active comparator and assessed pain intensity
      or pain-related disability as a primary outcome in patients with low back pain.
      Data Extraction: Two reviewers independently extracted data on study
      characteristics, patients, interventions, outcome measures, and results at short-
      and long-term follow-up. Risk of bias was assessed using the Cochrane risk-of
      bias tool. Data Synthesis: Seven RCTs involving 864 patients with low back pain
      were eligible for review. Compared with usual care, MBSR was associated with
      short-term improvements in pain intensity (4 RCTs; mean difference [MD], -0.96
      point on a numerical rating scale [95% CI, -1.64 to -0.34 point]; standardized
      mean difference [SMD], -0.48 point [CI, -0.82 to -0.14 point]) and physical
      functioning (2 RCTs; MD, 2.50 [CI, 0.90 to 4.10 point]; SMD, 0.25 [CI, 0.09 to
      0.41 point]) that were not sustained in the long term. Between-group differences
      in disability, mental health, pain acceptance, and mindfulness were not
      significant at short- or long-term follow-up. Compared with an active comparator,
      MBSR was not associated with significant differences in short- or long-term
      outcomes. No serious adverse events were reported. Limitation: The number of
      eligible RCTs was limited; only 3 evaluated MBSR against an active comparator.
      Conclusion: Mindfulness-based stress reduction may be associated with short-term
      effects on pain intensity and physical functioning. Long-term RCTs that compare
      MBSR versus active treatments are needed in order to best understand the role of
      MBSR in the management of low back pain. Primary Funding Source: None.

PMID- 28437792
TI  - Phase-plate cryo-EM structure of a class B GPCR-G-protein complex.
AB  - Class B G-protein-coupled receptors are major targets for the treatment of
      chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the
      structure of a full-length class B receptor, the calcitonin receptor, in complex
      with peptide ligand and heterotrimeric Galphasbetagamma protein determined by
      Volta phase-plate single-particle cryo-electron microscopy. The peptide agonist
      engages the receptor by binding to an extended hydrophobic pocket facilitated by
      the large outward movement of the extracellular ends of transmembrane helices 6
      and 7. This conformation is accompanied by a 60 degrees  kink in helix 6 and a
      large outward movement of the intracellular end of this helix, opening the bundle
      to accommodate interactions with the alpha5-helix of Galphas. Also observed is an
      extended intracellular helix 8 that contributes to both receptor stability and
      functional G-protein coupling via an interaction with the Gbeta subunit. This
      structure provides a new framework for understanding G-protein-coupled receptor
      function.

PMID- 28437794
TI  - Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy
      for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and
      Drug Administration Adverse Event Reporting System.
AB  - Background: Direct-acting antiviral agents (DAAs) are used increasingly to treat
      hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B
      virus (HBV) reactivation (HBV-R) in patients with HBV-HCV co-infection. Hepatitis
      B virus reactivation, defined as an abrupt increase in HBV replication in
      patients with inactive or resolved HBV infection, may result in clinically
      significant hepatitis. Objective: To assess whether HBV-R is a safety concern in
      patients receiving HCV DAAs. Design: Descriptive case series. Setting: U.S. Food
      and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Patients:
      29 patients with HBV-R receiving HCV DAAs. Measurements: Clinical and laboratory
      data. Results: The FDA identified 29 unique reports of HBV-R in patients
      receiving DAAs from 22 November 2013 to 15 October 2016. Two cases resulted in
      death and 1 case in liver transplantation. Patients in whom HBV-R developed were
      heterogeneous regarding HCV genotype, DAAs received, and baseline HBV
      characteristics. At baseline, 9 patients had a detectable HBV viral load, 7 had
      positive results on hepatitis B surface antigen (HBsAg) testing and had an
      undetectable HBV viral load, and 3 had negative results on HBsAg testing and had
      an undetectable HBV viral load. For the remaining 10 patients, data points were
      not reported or the data were uninterpretable. Despite provider knowledge of
      baseline HBV, HBV-R diagnosis and treatment were delayed in 7 cases and possibly
      7 others. Limitations: The quality of information varied among reports. Because
      reporting is voluntary, HBV-R associated with DAAs likely is underreported.
      Conclusion: Hepatitis B virus reactivation is a newly identified safety concern
      in patients with HBV-HCV co-infection treated with DAAs. Patients with a history
      of HBV require clinical monitoring while receiving DAA therapy. Studies would
      help determine the risk factors for HBV-R, define monitoring frequency, and
      identify patients who may benefit from HBV prophylaxis and treatment. DAAs remain
      a safe and highly effective treatment for the management of HCV infection.
      Primary Funding Source: None.

PMID- 28437796
TI  - Toward Optimal Control of Hepatitis C Virus Infection in Persons With Substance
      Use Disorders.

PMID- 28437795
TI  - Effect of Using the HEART Score in Patients With Chest Pain in the Emergency
      Department: A Stepped-Wedge, Cluster Randomized Trial.
AB  - Background: The HEART (History, Electrocardiogram, Age, Risk factors, and initial
      Troponin) score is an easy-to-apply instrument to stratify patients with chest
      pain according to their short-term risk for major adverse cardiac events (MACEs),
      but its effect on daily practice is unknown. Objective: To measure the effect of
      use of the HEART score on patient outcomes and use of health care resources.
      Design: Stepped-wedge, cluster randomized trial. (ClinicalTrials.gov:
      NCT01756846). Setting: Emergency departments in 9 Dutch hospitals. Patients:
      Unselected patients with chest pain presenting at emergency departments in 2013
      and 2014. Intervention: All hospitals started with usual care. Every 6 weeks, 1
      hospital was randomly assigned to switch to "HEART care," during which physicians
      calculated the HEART score to guide patient management. Measurements: For safety,
      a noninferiority margin of a 3.0% absolute increase in MACEs within 6 weeks was
      set. Other outcomes included use of health care resources, quality of life, and
      cost-effectiveness. Results: A total of 3648 patients were included (1827
      receiving usual care and 1821 receiving HEART care). Six-week incidence of MACEs
      during HEART care was 1.3% lower than during usual care (upper limit of the 1
      sided 95% CI, 2.1% [within the noninferiority margin of 3.0%]). In low-risk
      patients, incidence of MACEs was 2.0% (95% CI, 1.2% to 3.3%). No statistically
      significant differences in early discharge, readmissions, recurrent emergency
      department visits, outpatient visits, or visits to general practitioners were
      observed. Limitation: Physicians were hesitant to refrain from admission and
      diagnostic tests in patients classified as low risk by the HEART score.
      Conclusion: Using the HEART score during initial assessment of patients with
      chest pain is safe, but the effect on health care resources is limited, possibly
      due to nonadherence to management recommendations. Primary Funding Source:
      Netherlands Organisation for Health Research and Development.

PMID- 28437797
TI  - Central and peripheral vision for scene recognition: A neurocomputational
      modeling exploration.
AB  - What are the roles of central and peripheral vision in human scene recognition?
      Larson and Loschky (2009) showed that peripheral vision contributes more than
      central vision in obtaining maximum scene recognition accuracy. However, central
      vision is more efficient for scene recognition than peripheral, based on the
      amount of visual area needed for accurate recognition. In this study, we model
      and explain the results of Larson and Loschky (2009) using a neurocomputational
      modeling approach. We show that the advantage of peripheral vision in scene
      recognition, as well as the efficiency advantage for central vision, can be
      replicated using state-of-the-art deep neural network models. In addition, we
      propose and provide support for the hypothesis that the peripheral advantage
      comes from the inherent usefulness of peripheral features. This result is
      consistent with data presented by Thibaut, Tran, Szaffarczyk, and Boucart (2014),
      who showed that patients with central vision loss can still categorize natural
      scenes efficiently. Furthermore, by using a deep mixture-of-experts model ("The
      Deep Model," or TDM) that receives central and peripheral visual information on
      separate channels simultaneously, we show that the peripheral advantage emerges
      naturally in the learning process: When trained to categorize scenes, the model
      weights the peripheral pathway more than the central pathway. As we have seen in
      our previous modeling work, learning creates a transform that spreads different
      scene categories into different regions in representational space. Finally, we
      visualize the features for the two pathways, and find that different preferences
      for scene categories emerge for the two pathways during the training process.

PMID- 28437798
TI  - Making Do With What We Have.

PMID- 28437799
TI  - Normal-Weight Central Obesity and Risk for Mortality.

PMID- 28437800
TI  - It's Over, Debbie.

PMID- 28437801
TI  - [Regorafenib - a revolution in the systemic treatment options of HCC?]

PMID- 28437802
TI  - Surveillance after resection of pancreatic ductal adenocarcinoma with curative
      intent - a multicenter survey in Germany and review of the literature.
AB  - Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal
      cancers with high risk of relapse even after curative-intended resection. There
      are no evidence-based recommendations for surveillance in actual guidelines.
      Given this situation and as a basis for prospective studies, we wanted to
      determine the current practice of surveillance after pancreatic cancer resection
      in German institutions. Methods A web-based questionnaire was sent in 2015 to 300
      German institutions (hospitals, outpatient clinics, and private practices)
      experienced in the care of patients with PDAC. The questionnaire comprised 23
      items including the respective institution, the level of care, the annual case
      load of pancreatic cancer surgery, the surveillance algorithms used, and the most
      frequently used means for surveillance as well as their evaluation by the users
      with respect to the effectiveness of these means. Additionally, we perform a
      review of the literature. Results The final analysis comprised 161 questionnaires
      (response rate 53.7 %). Mainly high-volume centers (82.5 % with > 300 hospital
      beds) participated. In 46.6 % of centers, more than 80 % of patients received
      adjuvant chemotherapy after surgery. Between 60 - 80 % of these patients
      completed the recommended 6 months of adjuvant treatment, and 47 % of the
      patients received the whole treatment (surgery, adjuvant therapy) and
      surveillance in the same center. Upon completion of adjuvant treatment, 96 % of
      centers survey their patients, and 82 % of these centers already employ
      diagnostic means during the course of adjuvant chemotherapy. The most commonly
      used diagnostic means were taking patient history, conducting physical
      examination, performing laboratory tests including CA19 - 9, and imaging. Of
      those employed, CA19 - 9 and imaging followed by patient history were considered
      the most efficient to detect disease relapse by the centers. Half of the
      institutions perform surveillance for 5 years after surgery. Conclusion This is
      the first systematic analysis of self-reported surveillance strategies used in
      Germany after resection of PDAC with curative intent. Surveillance after
      resection of PDAC with curative intent is common in Germany. Alterations of CA19 
      9 levels as well as imaging and taking patient history are considered the most
      efficient means to detect relapse of disease by the physicians participating in
      our survey.

PMID- 28437803
TI  - Prevalence of Helicobacter pylori infection among blood donors in Saxony-Anhalt,
      Germany - a region at intermediate risk for gastric cancer.
AB  - Background In the federal state of Saxony-Anhalt, gastric cancer (GC) incidence
      ranks among the highest in Germany. Helicobacter pylori prevalence is a surrogate
      marker for GC risk in a given population. In 2010 we reported an H. pylori
      seroprevalence of 44.4 % in patients at the emergency ward of the University
      Hospital of Magdeburg, the capital of Saxony-Anhalt. Our aim is to update these
      findings in a cohort of healthy blood donors from the same region. Materials and
      methods The sera of 516 consecutive blood donors (40.1 +/- 14.1 years; 286 males
      and 230 females) were tested for antibodies against H. pylori and CagA. Data on
      demographics and previous H. pylori eradication therapy were obtained by means of
      a structured questionnaire. Blood donors with positive serology for H. pylori or
      CagA and/or history of eradication therapy were classified as H. pylori-positive.
      Results Overall, 28.9 % of the study cohort were H. pylori-positive. The
      prevalence was higher in older generations (9 % in 18 - 20 years up to 47 % in 61
      - 70 years). In 44.4 % of H. pylori IgG-positive donors, CagA serology was also
      positive. This proportion was not age-dependent. Study participants with siblings
      were by trend more often H. pylori-positive (p = 0.066). Conclusion Compared to
      our previous study in patients at the emergency ward, we found by trend lower age
      related H. pylori prevalence rates. In our cohort of healthy blood donors, we
      confirmed a lower H. pylori prevalence in younger generations.

PMID- 28437804
TI  - [Prognostic Factors of Open Abdomen Treatment in Visceral Surgery].
AB  - Introduction In general surgery, open abdomen treatment (OAT) is used to treat
      abdominal compartment syndrome (ACS) and sepsis, often after a primary surgical
      procedure associated with complications. The results achieved in this patient
      population may depend on factors that are yet unknown. This study evaluates
      independent patient-related prognostic factors after OAT. Methods 38 clinical
      parameters and survival data of 165 consecutive general surgery patients after
      OAT were entered into a prospective database according to a defined algorithm in
      order to analyse the underlying surgical pathology, predictors of survival and
      important aspects of OAT-related morbidity. Independent predictors of survival,
      OAT-related morbidity and duration of hospital stay were identified. Results
      Common indications for OAT were peritonitis, haemorrhage and ACS. Median age was
      60 years and > 80 % of patients were ASA III/IV; median follow-up was 23 months.
      Oncologic surgery was performed in 19 % of cases. 30-day and 1-year mortality was
      11 % and 34 %, respectively. Malignancy was a negative predictor (OR: 4.63, 95 %
      CI: 2.00-10.7) while mild obesity (BMI 25-35) and primary fascial closure, which
      was achieved in 82 % of patients, improved survival (OR: 0.2, 95 % CI: 0.07-0.55;
      OR: 0.19, 95 % CI: 0.06-0.57). Enteroatmospheric fistula (EAF) and giant hernia
      with impossible fascial closure were frequent after OAT (19 and 18 %), and
      malignancy was an independent risk factor for EAF (OR 3.47, CI [95 %]: 1.41
      8.53). Vacuum-assisted wound closure or polyglactin mesh interposition did not
      affect EAF incidence. Conclusions General surgery patients after OAT differ
      significantly from trauma patients, and mortality as well as long-term morbidity
      is high. Outcome is greatly determined by independent patient-related factors
      after OAT. A tailored surgical approach based on objective evidence is needed to
      further improve the results after OAT.

PMID- 28437805
TI  - Anti-inflammatory, Antipyretic, and Antinociceptive Effects of a Cressa cretica
      Aqueous Extract.
AB  - Cressa cretica is a widely grown halophytic plant traditionally used for the
      treatment of different ailments. Previous investigations reported its biological
      activity on a wide spectrum of diseases. In this study, in vivo antinociceptive,
      anti-inflammatory, and antipyretic activities of C. cretica aqueous extract whole
      plant were evaluated. In addition, the total polyphenol content, the total
      flavonoid content, and the chemical characterization of the extract were
      performed. C. cretica showed writhing inhibition in acetic acid-induced
      peripheral nociception of 43 and 48 % at doses of 50 and 100 mg/kg, respectively.
      The same doses increased latency time in a hot plate model of central analgesia
      by 66 and 78 % compared to the control group, respectively. The acute anti
      inflammatory effect of the extract was explored in the carrageenan-induced rat
      hind paw test. The inhibition of paw volume was better than that of the standard
      drug indomethacin. C. cretica significantly decreased rectal temperature in the
      rats injected with Brewer's yeast. C. cretica aqueous extract showed both central
      and peripheral antinociceptive activities and was effective as an anti
      inflammatory and antipyretic. Phenolic compounds, including chlorogenic acids and
      flavonol glycosides, were identified by HPLC-PDA-ESI-MS techniques. These
      findings indicate the medicinal importance of this traditionally used plant as a
      therapeutic remedy for different ailments.

PMID- 28437806
TI  - Potential of Bryophyllum pinnatum as a Detrusor Relaxant: An in Vitro Exploratory
      Study.
AB  - An earlier prospective, randomised, placebo-controlled clinical trial had
      suggested that Bryophyllum pinnatum might have potential in the treatment of
      overactive bladder. Here we investigated the effects of B. pinnatum leaf press
      juice, fractions enriched in flavonoids and bufadienolides, and a flavonoid
      aglycon mixture and individual aglycons on detrusor contractility as a major
      target in overactive bladder treatment. The strength of the detrusor contractions
      was investigated using porcine muscle strips stimulated with KCl. B. pinnatum
      leaf press juice increased the contraction force of muscle strips. Treatment with
      the flavonoid-enriched fraction had almost no effect on contractility, while the
      bufadienolide-enriched fraction and flavonoid aglycons led to a concentration
      dependent lowering of the contraction force. The data indicate that several
      components of B. pinnatum leaf press juice may contribute to the inhibitory
      effect on detrusor contractility, which in turn provides support to overactive
      bladder treatment with B. pinnatum.

PMID- 28437807
TI  - When the Evidence is not Enough: Commentary on Hartel-Petri et al.

PMID- 28437808
TI  - [Unilateral Supraclavicular Swelling during Pregnancy].

PMID- 28437809
TI  - Reactive Rather than Proactive Diabetes Management in the Perioperative Period.
AB  - As perioperative hyperglycemia is associated with poor postoperative patient
      outcomes, clinical guidelines provide recommendations for optimal perioperative
      glucose control. It is unclear to what extent recommended glucose levels are met
      in daily practice, and little is known about factors that influence these levels.
      We describe blood glucose levels throughout the hospital care pathway in 375 non
      critically ill patients with diabetes who underwent major surgery (abdominal,
      cardiac, or orthopedic) in 6 hospitals, examine determinants of these levels
      including adherence to 9 quality indicators for optimal perioperative diabetes
      care, and perform qualitative interviews to identify barriers for optimal care.
      Virtually all patients (95%) experienced at least one hyperglycemic value (>10
      mmol/l); 9% had at least one value <4 mmol/l. Mean glucose increased from
      preoperative to postoperative day (POD) 1 (+2.3 mmol/l, 5-95% CI 1.9-2.7), and
      then gradually decreased on POD 2-14 (+1.8 mmol/l, 5-95% CI 1.4-2.2). Insulin
      treated patients (with or without oral agents) had higher glucose levels (+1.7
      mmol/l, 5-95% CI 0.5-3.0, and +1.2 mmol/l, -0.1 to -2.5) than patients using oral
      agents only. Indicator adherence tended to be associated with higher glucose
      levels. Barriers for optimal care included a lack of formalized agreements on
      target glucose levels, absence of directly obvious disadvantages of
      hyperglycemia, and concern about inducing hypoglycemia. Hyperglycemia is common
      after major surgery, in particular on POD1 and in insulin-treated patients. Our
      results suggest that perioperative diabetes care is reactive rather than
      proactive, and that current emphasis of professionals is on treating instead of
      preventing postoperative hyperglycemia.

PMID- 28437810
TI  - Hyperprolactinemia and the Association with All-Cause Mortality and
      Cardiovascular Mortality.
AB  - Hyperprolactinemia has been suspected to increase mortality risk, but the
      available data are conflicting. The objective of this study was to estimate the
      association between hyperprolactinemia and all-cause and cardiovascular mortality
      among patients referred for assessment of prolactin. For this study, adults with
      no prio pituitary disease who underwent prolactin assessment at 3 university
      Hospitals in Denmark between 2001 and 2011 were included in a retrospective
      cohort study. A total of 3 633 patients with a median follow-up time of 5.3 years
      (IQR 2.7-5.7) were included. Mean (SD) age 39.7 (15.5) years and 78% female.
      373/3 633 (10.3%) had hyperprolactinemia and during follow-up 330/3 633 (9.1%)
      patients died of any cause, and 113/3 633 (3.1%) patients died of cardiovascular
      causes. In males, hyperprolactinemia was associated with age-adjusted incidence
      rate ratio (IRR) of 1.86 for all-cause mortality (95% CI 1.22-2.82) and 2.55 (95%
      CI 1.43-4.55) for cardiovascular mortality. The IRR for all-cause mortality was
      reduced to 1.37 (0.90-2.08) when adjusted for the use of antipsychotic
      medication. The association between hyperprolactinemia and cardiovascular
      mortality remained after adjusting for confounders, for example, chronic renal
      failure, diabetes, and antipsychotic medication. In females, hyperprolactinemia
      was not associated with all-cause mortality (IRR 1.45; CI 0.86-2.47) or
      cardiovascular mortality (IRR 0.58; CI 0.14-2.39). In conclusion,
      hyperprolactinemia was associated with increased cardiovascular mortality in male
      patients. This association was not found in female patients. Focus on increased
      cardiovascular risk in males with hyperprolactinemia is warranted.

PMID- 28437811
TI  - Symptomatic Outcome after Bone-only Suboccipital Decompression in Adult Patients
      with Chiari Type I Malformations in the Absence of Hydromyelia or Hydrocephalus.
AB  - Background Type I Chiari malformation presents without an associated hydromyelia
      in 30 to 70% of cases, yet there is no agreement regarding the optimal surgical
      treatment for these patients. We review our experience for treating symptomatic
      adult type I Chiari malformation without hydromyelia using a suboccipital bone
      decompression of the hindbrain and no duraplasty in 12 adult patients. Outcome
      was measured according to the Chicago Chiari Outcome Scale (CCOS). Results Nine
      of 12 patients were female; average age at surgery was 34.4 years (range: 17-67
      years). Average duration of symptoms prior to surgery was 9.6 years (2 months-29
      years). The most common symptom was head and/or neck pain (11/12 patients). All
      patients additionally presented with at least one non-pain symptom. Mean degree
      of tonsillar herniation on magnetic resonance imaging was 6.8 mm (range: 5-12 mm)
      below McRae's line. Operative time was on average 68 minutes (range: 47-120
      minutes). No surgical complications were noted in any patient. Length of hospital
      stay was 2 days (1 overnight) for all patients. Mean follow-up was 167 weeks
      (range: 13-378 weeks). CCOS for all patients on average was 14.50 (range: 12-16).
      Pain symptoms underwent improvement (7/11 [63.6%]) or complete resolution (4/11
      [36.4%]) in all affected patients. A shorter duration of preoperative symptoms
      significantly correlated with a better CCOS (p = 0.03). Degree of tonsillar
      herniation had no significant effect on CCOS (p = 0.67). Of non-pain symptoms,
      paresthesias/dysesthesias and visual symptoms improved or resolved completely in
      all affected patients. No patient experienced a worsening of either pain or non
      pain symptoms. Conclusion In the subset of adult patients with a type I Chiari
      malformation and no associated hydromyelia, a craniectomy without an additional
      opening of the dura may achieve good overall results according to the CCOS.

PMID- 28437812
TI  - Infection Rate in 1033 Elective Neurosurgical Procedures at a University Hospital
      in South China.
AB  - Objective Infection following surgery is a serious complication, especially in
      neurosurgery. The aim of the study is to report the change of incidence rates of
      infection in patients undergoing elective neurosurgical procedures at a
      university hospital in South China as well as the risk factors. Material and
      Methods The medical records and postoperative courses for patients undergoing
      1,033 neurosurgical procedures from 2008 to 2014 were reviewed retrospectively to
      determine the incidence of neurosurgical infection, the identity of the offending
      organisms, and the factors associated with infection. Results A total of 33
      patients (40 cases) experienced postoperative infection representing 3.19% of the
      study population. Twenty cases were incision infections (1.94%), and 20 were
      cranial/spinal infections (1.94%) including 15 intracranial infections and 5
      intraspinal infections. The 2.4-fold greater incidence of postoperative infection
      in 2008 to 2010 was compared with that in 2011 to 2014 with perioperative
      antibiotic prophylaxis (p <0.01). The neurosurgical procedure associated with the
      highest rate of infection was cranioplasty (6.85%); the lowest rate of infection
      was associated with functional neurosurgery (1.08%). The most common offending
      organism was Staphylococcus aureus (27.5%). Foreign body implantation, operative
      time > 4 hours, and cerebrospinal fluid (CSF) leak (13 infections in 158
      patients; p <0.001) were risk factors for infections (p <0.05). Conclusion The
      neurosurgical infection rate is usually low with perioperative antibiotic
      prophylaxis even in developing countries. Less foreign body implantation, shorter
      operative times, and controlling CSF leak could reduce infection rates.

PMID- 28437813
TI  - Presenting Symptoms of Pituitary Apoplexy.
AB  - The classical term "pituitary apoplexy" (PA) describes a clinical syndrome
      usually characterized by abrupt onset of headache accompanied by neurologic
      and/or endocrinologic deterioration due to sudden expansion of a mass within the
      sella turcica as a result of hemorrhage or infarction within a pituitary tumor
      and adjacent pituitary gland. PA is a medical emergency and a difficult diagnosis
      to establish. Thus this article reviews the presenting symptoms of PA patients to
      help clinicians recognize or at least suspect this critical condition early on.
      PA commonly occurs in the setting of a preexisting adenoma, and several patients
      are unaware of its existence prior to the onset of apoplexy symptoms, which are
      mainly of a neurologic, ophthalmologic, and endocrinologic nature. Neurologic
      symptoms include sudden-onset severe headache and other symptoms of subarachnoid
      hemorrhage, symptoms from compression of the cavernous sinus contents,
      nausea/vomiting, impaired consciousness, and symptoms of meningeal irritation.
      Ophthalmologic symptoms include visual field defects, visual loss, diplopia, and
      ophthalmoplegia. Endocrinologic disturbances include pituitary adenoma symptoms,
      cortisol deficiency, panhypopituitarism, diabetes insipidus, and syndrome of
      inappropriate secretion of antidiuretic hormone. Magnetic resonance imaging is
      the imaging method of choice to aid the PA diagnosis. Its differential diagnoses
      include cerebrovascular accidents, infectious diseases, and other causes of
      endocrinologic imbalance. Transsphenoidal surgery is the treatment of choice,
      especially if there are associated visual abnormalities and ophthalmoplegia.
      Clinicians should be aware of the presenting symptoms because early diagnosis may
      reduce the morbidity and mortality of this neurosurgical emergency.

PMID- 28437814
TI  - Assessment of Early Cardiovascular Risk in Children and Adolescents with
      Essential Hypertension.
AB  - The aim of our study was to investigate some early markers of hypertensive target
      organ damage in hypertensive children and adolescents, and to detect those
      showing most prominent clinical significance. We included 100 children with
      essential hypertension (EH) and 50 age-matched healthy control children, and
      evaluated left ventricular mass (LVM), intima-media thickness in the carotid
      arteries (IMT), pulse wave velocity (PWV), microalbuminuria, biochemical
      parameters and some adipokines. Statistically significant differences between the
      2 groups were observed for HDL-cholesterol, LDL-cholesterol, triglycerides,
      insulin, uric acid, glucose, apolipoprotein A1, and total adiponectin. The mean
      values of IMT, PWV and LVM were greater in hypertensive children, but only the
      differences in IMT and LVM were statistically significant. In addition,
      hypertensive children showed significantly higher values of AoSP (aortic systolic
      pressure), AoPP (aortic pulse pressure) and AIx@75 (augmentation index corrected
      for heart rate of 75 b.p.m.). Metabolic syndrome was diagnosed in 31% of
      hypertensive children. A significant number of children with EH have early target
      organ changes as well as other risk factors, including metabolic syndrome,
      especially obese ones. However, IMT, LVM and some parameters of arterial
      stiffness have been found to be early markers in both obese and non-obese
      hypertensives. In addition, adipokines and coagulation factors seem to be
      important in obese hypertensives.

PMID- 28437815
TI  - [Cancer Related Fatigue in Rehabilitation Care].
AB  - Aim of the study was to provide information about the prevalence of cancer
      related fatigue and the association between treatment-related factors and fatigue
      in cancer patients during the rehabilitation care. In a multicenter study 693
      cancer patients (27% breast cancer, 17% prostate cancer etc.) completed the
      Multidimensional Fatigue Inventory (MFI-20) and sociodemographic and treatment
      information was noted. 51% of the patients suffer from fatigue (n=356). Fatigue
      prevalence differed according to tumour localization (p<=0.001). There was a
      substantial association between fatigue and treatment condition in terms of the
      combination of surgery and radiation (p<=0.05). Fatigue was high prevalent in
      patients in the rehabilitation care. Thus, fatigue should be routinely screened
      and after differentiated diagnostics be considered in rehabilitation care plans.

PMID- 28437816
TI  - [Subjective Level of Information and Information Needs of Patients with an
      Approved Rehabilitation Application and Patients at the End of Rehabilitation
      Results of a Written Survey].
AB  - AimThe aim of the study was to identify the subjective level of information and
      information needs of patients with an approved rehabilitation application and
      patients at the end of rehabilitation with regard to preferred subjects and kind
      of information transfer. Method Written survey with N=283 patients with approved
      rehabilitation application and N=388 patients at the end of rehabilitation.
      ResultsBoth groups reported high information needs particularly regarding
      treatments during rehabilitation, rehabilitation aftercare and rehabilitation
      aims. A conversation with their physician, a brochure and a website are the
      preferred information pathways. Conclusion Taking into account the topics for
      which both groups require information and the preference regarding the kind of
      information transfer can make a valuable contribution for the development of
      needs-oriented information material.

PMID- 28437817
TI  - [Challenges of Diversity-Sensitive Care in Medical Rehabilitation].
AB  - Diversity markers such as sex, migration background and socioeconomic status are
      associated with different needs and expectations in health care. In
      rehabilitation these needs and expectations are often not adequately accounted
      for. This may affect health care outcomes. In order to improve rehabilitative
      care, it is not sufficient to only focus on selected diversity criteria such as
      migration background. This has two reasons: First, health care users are defined
      by a wide range of different diversity markers; second, diversity markers are
      closely interrelated. Diversity management allows to address the population as a
      whole by establishing conditions in health care institutions which permit to
      cater for the diversity of all health care users, thereby allowing to provide a
      more patient-oriented health care.

PMID- 28437818
TI  - [Towards a Rehabilitation- and Participation-Oriented Psychotherapy].
AB  - Mental disorders (such as recurrent mood disorders, personality disorders, or
      psychotic disorders) come along with enduring impairment in daily life
      activities. Therefore psychotherapeutic actions in inpatient or outpatient
      settings require a life-span and participation-oriented treatment perspective.
      Participation-oriented treatment aims at social and vocational integration in
      general life despite enduringly recurring or resting symptoms. According to the
      model of health problems offered by the International Classification of
      Functioning, Disability and Health, ICF (WHO, 2001), disability can be defined as
      context-dependent activity impairment due to illness. Disability is not the
      persons illness itself, but depends on the interaction of health status and
      contextual conditions. This context-dependent impairment shall be overcome with
      the help of treatment. In psychotherapy, the perspective of participation over
      the life-span has always been of great importance. However, it has until now
      hardly been mentioned explicitly.For practical handling of the ICF philosophy,
      its bio-psycho-social model of health problem-description is useful.
      Psychotherapists should gain knowledge on medical, vocational, and social
      rehabilitation treatment aims, institutions and the health care system.
      Psychotherapists may serve, similar to family physicians, as a case manager of
      illness processes. They do not only aim reducing mental illness symptoms, but
      focus on life-span management of the mental disorder. The aim is mainly to
      improve patients daily life participation.

PMID- 28437819
TI  - [Working and mental illness - Do digitalisation and globalisation make us ill?]

PMID- 28437820
TI  - [Therapy of Hemifacial Spasm with Botulinum Toxin].
AB  - Hemifacial spasm (HFS) is a frequent disorder characterized by involuntary
      contractions of those muscles innervated by the facialis nerve on one side of the
      face. The symptoms can appear as tonic or clonic, intermittent or permanent.
      Diagnosis is based purely on clinical observation. Differential diagnosis should
      rely on cranial MRI, which can demonstrate a pathological contact between the
      nerves and vessels and exclude alternative causation. Often, the symptoms are not
      marked so that therapy may not be necessary. The therapy of choice is an
      injection of botulinum toxin to reduce the underlying pathological activity. As
      an alternative, decompression operation according to Jannetta can be considered,
      although it is frequently rejected by patients.

PMID- 28437821
TI  - [Rapid Cycling in Bipolar Disorders: Symptoms, Background and Treatment
      Recommendations].
AB  - Rapid cycling bipolar disorder is encountered frequently in clinical practice
      with a lifetime prevalence of up to 31 %. Besides its association with greater
      illness severity, increased suicide and comorbidity rates, rapid cycling bipolar
      disorder has been closely associated with a longer and more complicated course of
      disease and inadequate treatment response compared to non-rapid cycling bipolar
      disorder. However rapid cycling does not serve as a stable characteristic of
      bipolar disorder, though its prevalence increases with illness duration. Female
      gender, hypothyreoidism and antidepressant medications have been suggested as
      correlates of rapid cycling bipolar disorder; however, the interaction amongst
      these factors make an interpretation of their causal relations difficult. Only
      very few data are available from randomized clinical trials that investigated the
      therapeutic options of rapid cycling bipolar disorder. Based on these trials, the
      therapeutic outcome of lithium is similar to that of the class of
      anticonvulsants. Positive treatment outcome reported for atypical neuroleptics is
      often based on pharmaceutical company-financed, placebo-controlled RCTS.
      Altogether independent prospective RCTs and head-to-head comparisons are lacking
      that can provide sufficient information on treatment response. In addition, the
      role of antidepressant treatment in the course and phase acceleration of bipolar
      disorder remains insufficiently understood. However, in the light of present
      empirical evidence, the use of antidepressant medication in the treatment of
      rapid cycling bipolar disorder has to be looked at highly critically.

PMID- 28437822
TI  - Osmotic Demyelination Syndrome due to Severe Hyponatremia Mimicking Hypoxic
      Encephalopathy.
AB  - Hyponatremia and its rapid correction is a well-known cause of osmotic
      demyelination most commonly affecting the pons. We report on a case of severe
      hyponatremia likely due to psychogenic polydipsia resulting in hypotonic
      hyperhydration with resulting cortical laminar necrosis on initial imaging,
      mimicking hypoxic brain damage. Pontine myelinolysis became apparent on follow-up
      imaging, illustrating the diagnostic challenges of extrapontine manifestations of
      severe hyponatremia.

PMID- 28437823
TI  - [Medicolegal Assessment of Psychic Sequelae after Minor Traumatic Events].
AB  - The majority of medicolegal assessments in claimed psychic sequelae after
      accidents concerns minor traumatic events. In this case, the focus is on three
      questions: Was the event appropriate to cause a traumatic disturbance according
      to current psychiatric classification systems (especially current DSM-5)? Which
      psychical or physical initial injury can be proven beyond reasonable doubt ("full
      proof") according to German law? What is the impact of personality
      characteristics and competing life events in the development and maintenance of
      the mental disorder? Causality between mental disorders and minor traumatic
      events is to be confirmed especially in the case of persistent physical accident
      sequelae, but attention has to be paid to the differences in the various legal
      requirements.

PMID- 28437824
TI  - [Neuromodulation for the Treatment of Chronic Pain - What is Useful?]
AB  - Neuromodulatory techniques have replaced the earlier performed neurolesional
      procedures to treat chronic pain syndromes with only a few exceptions.
      Nevertheless these procedures are invasive with respective risks and
      complications and therefore conservative physical, psychological pharmacological
      as well as interventional treatments should be performed first. Because this
      therapy is costly, the indication has to be proven carefully with a strict
      patient selection and also the long-term results have to be considered. The
      following paper will give an overview over the recent neuromodulatory techniques,
      their indications and and published results.

PMID- 28437825
TI  - [Quality of Life and Functional Outcome after Microsurgical Decompression in
      Lumbar Spinal Stenosis: a Register Study].
AB  - Introduction Because of recent increases in life expectancy, lumbar spinal
      stenosis (LSS) has become one of the most common degenerative changes in the
      spine. In patients not responding to conservative therapy, microsurgical
      decompression is the gold standard of operative treatment for degenerative LSS.
      The goal of the current study is to evaluate quality of life after microsurgical
      decompression for LSS, using data from the DWG Register (previously Spine Tango).
      Methods 36 patients were included in this single-center, prospective,
      observational study from January 2013 to June 2014. Data were collected from the
      Spine Tango or DWG Register. The core outcome measure index (COMI), Oswestry
      Disability Index (ODI), and the quality of life questionnaire EuroQoL-5D were
      used. Data were collected prior to surgery as well as six weeks, six months, and
      twelve months after the operation. Results The patient cohort comprised 13
      females and 23 males (36.1 and 63.9 %). Complete 12-month follow-up data on 21
      patients were available for analysis. Compared to preoperative measures, the COMI
      score increased 8.1 +/- 1.5 over the entire follow up, with 4.5 +/- 3.1 at 6
      weeks (p < 0.001), 4.8 +/- 3.1 at 6 months, and 3.8 +/- 3.2 at 12 months. ODI
      scores, measuring spinal function impairment, were significantly better than
      preoperative values overall (47.5 +/- 17.3) and after 6 weeks (29.1 +/- 22.4; p <
      0.005), 6 months (30.0 +/- 19.3), and 12 months (23.8 +/- 18.2). Quality of life
      measures improved in a similar manner (preoperative: 0.36 +/- 0.38; 6 weeks: 0.57
      +/- 0.34 (p < 0.019); 6 months: 0.62 +/- 0.28; 12 months: 0.67 +/- 0.31).
      Conclusion Our study shows that LSS patients without previous surgery and
      neurologic deficits can expect significant pain relief and improved quality of
      life already six weeks after undergoing stabilizing decompression. There was an
      increase in positive postoperative effects over 12 months. The DWG Register
      provides a standardized and validated means to compare non-operative and
      operative treatments of the spine over the long term.

PMID- 28437826
TI  - Normal Left Ventricular Size in Premature Newborns by the Echocardiographic
      Bullet Method.

PMID- 28437827
TI  - [In process].

PMID- 28437829
TI  - [In process].

PMID- 28437828
TI  - [In process].

PMID- 28437830
TI  - [In process].

PMID- 28437831
TI  - [In process].

PMID- 28437832
TI  - Neuromuscular images: A picture can be worth more than a thousand words.

PMID- 28437833
TI  - Transient receptor potential channels and exercise-associated muscle cramping: A
      tale of multiple complexities.

PMID- 28437834
TI  - Elucidation of Factor VIII Activity Pharmacokinetics: A Pooled Population
      Analysis in Patients With Hemophilia A Treated With Moroctocog Alfa.
AB  - This study investigated the disposition of coagulation factor VIII activity in
      754 patients with moderate to severe hemophilia A following the administration of
      moroctocog alfa, a B-domain deleted recombinant factor VIII. Data analyzed
      included patients aged 1 day to 73 years enrolled in 13 studies conducted over a
      period of 20 years in 25 countries. A two-compartment population pharmacokinetic
      model with a baseline model described the pooled data well. Body size, age,
      inhibitors, race, and analytical assay were identified as significant predictors
      of factor VIII disposition. In addition, simulations of prophylactic dosing
      schedules in several pediatric cohorts showed large variability and suggest that
      younger patients would require higher weight-adjusted doses than adolescents to
      achieve target factor VIII trough activity when receiving every other day or
      twice weekly dosing.

PMID- 28437835
TI  - PTEN Down-Regulation Promotes beta-Oxidation to Fuel Hypertrophic Liver Growth
      After Hepatectomy in Mice.
AB  - : In regenerating liver, hepatocytes accumulate lipids before the major wave of
      parenchymal growth. This transient, regeneration-associated steatosis (TRAS) is
      required for liver recovery, but its purpose is unclear. The tumor suppressor
      phosphatase and tensin homolog (PTEN) is a key inhibitor of the protein kinase
      B/mammalian target of rapamycin axis that regulates growth and metabolic
      adaptations after hepatectomy. In quiescent liver, PTEN causes pathological
      steatosis when lost, whereas its role in regenerating liver remains unknown.
      Here, we show that PTEN down-regulation promotes liver growth in a TRAS-dependent
      way. In wild-type mice, PTEN reduction occurred after TRAS formation, persisted
      during its disappearance, and correlated with up-regulated beta-oxidation at the
      expense of lipogenesis. Pharmacological modulation revealed an association of
      PTEN with TRAS turnover and hypertrophic liver growth. In liver-specific Pten-/-
      mice shortly after induction of knockout, hypertrophic regeneration was
      accelerated and led to hepatomegaly. The resulting surplus liver mass was
      functional, as demonstrated by raised survival in a lethal model of resection
      induced liver failure. Indirect calorimetry revealed lipid oxidation as the
      primary energy source early after hepatectomy. The shift from glucose to lipid
      usage was pronounced in Pten-/- mice and correlated with the disappearance of
      TRAS. Partial inhibition of beta-oxidation led to persisting TRAS in Pten-/- mice
      and abrogated hypertrophic liver growth. PTEN down-regulation may promote beta
      oxidation through beta-catenin, whereas hypertrophy was dependent on mammalian
      target of rapamycin complex 1. CONCLUSION: PTEN down-regulation after hepatectomy
      promotes the burning of TRAS-derived lipids to fuel hypertrophic liver
      regeneration. Therefore, the anabolic function of PTEN deficiency in resting
      liver is transformed into catabolic activities upon tissue loss. These findings
      portray PTEN as a node coordinating liver growth with its energy demands and
      emphasize the need of lipids for regeneration. (Hepatology 2017;66:908-921).

PMID- 28437836
TI  - Nurses' Attitudes Toward the Single Checking of Medications.
AB  - BACKGROUND AND AIM: The policy of single over double checking of medications has
      been adopted by many health services; however, nurses' attitudes toward single
      checking medications remains unclear. The aim of this study was to explore the
      attitudes of nurses who single check and administer medications in a setting
      where single checking has been in place for over a decade. METHODS: A cross
      sectional survey design using the validated Single Checking Administration
      Medication Scale-II to registered nurses (n = 299) working in one metropolitan
      teaching hospital in Victoria, Australia. Descriptive analyses for participants'
      demographics were examined and confirmatory factor analysis (CFA) was performed
      on the survey items to represent the main themes of nurses' attitudes toward
      single checking. RESULTS: Nurses reported single checking allowed a greater
      accountability as a professional nurse and more control over drug administration.
      The efficiency of single checking was welcomed by nurses through reductions in
      administration time and workplace interruptions. Nurses were more likely to
      adhere to drug administration procedures when single checking and this process
      facilitated drug knowledge updates. There was significant variance in attitudes
      amongst nurses based upon current appointment and years of clinical experience.
      Free text responses indicated nurses' attitudes were situated in the context of
      the traditional double-checking system. LINKING EVIDENCE TO ACTION: Understanding
      nurses' attitudes toward single checking may assist health care services to
      positively address medication safety. Accountability, efficiency and knowledge
      are important for nurses when administering medications. Nurses' attitudes are
      varied when correlated with demographic characteristics.

PMID- 28437837
TI  - Family Planning Counseling for Women With Rheumatic Diseases.

PMID- 28437838
TI  - Prognostic relevance of miR-124-3p and its target TP53INP1 in pediatric
      ependymoma.
AB  - Ependymoma is a malignant pediatric brain tumor, often incurable under the
      current treatment regimen. We aimed to evaluate the expression of microRNAs
      (miRs) in pediatric ependymoma tumors in an attempt to identify prognostic
      molecular markers which would lead to potential therapeutic targets. Following
      miR-array expression analysis, we focused on 9 miRs that correlated with relapse
      which were further validated by quantitative real-time PCR (qRT-PCR) in a cohort
      of 67 patients. Western blotting and immunohistochemistry were used to measure
      target protein expression in 20 and 34 tumor samples, respectively. High
      expression of miR-124-3p significantly correlated with the lower progression-free
      survival (PFS) of 16% compared to 67% in those expressing low levels (P = .002).
      Interestingly, in the group of patients with local disease (n = 56) expression
      levels of this miR distinguished 2 subgroups with a significantly different
      outcome (P = .001). miR-124-3p was identified as an independent prognostic factor
      of relapse in the multivariate analysis performed in the whole cohort and in the
      group with localized disease. In the localized group, a patient expressing high
      levels of miR-124-3p had a 4.1-fold increased risk for relapse (P = .005). We
      demonstrated the direct binding of miR-124-3p to its target TP53INP1. Negative
      TP53INP1 protein levels correlated with a poor outcome (P = .034). We propose miR
      124-3p and TP53INP1 as new biomarkers for prognostic stratification that may be
      possible therapeutic targets for ependymoma.

PMID- 28437839
TI  - Inhibition of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1
      reduces lipopolysaccharide-induced neuroinflammation.
AB  - BACKGROUND AND PURPOSE: Neuroinflammation is initiated by a variety of stimuli
      including infections, sepsis, neurodegenerative diseases or traumatic brain
      injury and, if not adequately controlled, can lead to various degrees of neuronal
      damage and behavioural impairment. A critical event in the initial steps of
      inflammation is neutrophil extravasation. Semicarbazide-sensitive amine oxidase
      (SSAO, also known as vascular adhesion protein 1 or VAP-1) regulates neutrophil
      adhesion and extravasation. Here, we elucidate the role of SSAO/VAP-1 in the
      early stage inflammatory response after LPS insult in the brain. EXPERIMENTAL
      APPROACH: PXS-4681A, a selective and irreversible SSAO/VAP-1 inhibitor, was
      tested in two rat models of neuroinflammation, following systemic or i.c.v. LPS.
      Immunohistochemical and immunofluorescence techniques were used to measure
      neutrophils and microglia. VAP-1 was quantitated by Western blotting. KEY
      RESULTS: Both systemic and i.c.v. administration of LPS induced an increase in
      neutrophil recruitment and microglial response in various brain areas including
      the substantia nigra and striatum. PXS-4681A produced a significant inhibition of
      neutrophil recruitment and extravasation after i.c.v. LPS injection and also
      reversed microglial cell recruitment and morphological changes to the level of
      the sham controls in both LPS models. CONCLUSIONS AND IMPLICATIONS: PXS-4681A
      acted as an effective anti-inflammatory agent after both systemic and i.c.v. LPS
      injections suggesting that SSAO/VAP-1 inhibition could be beneficial in the
      treatment of brain inflammation.

PMID- 28437840
TI  - Blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms and risk
      of amyotrophic lateral sclerosis: A more than 20-year follow-up of the Swedish
      AMORIS cohort.
AB  - OBJECTIVE: To assess the associations of blood biomarkers of carbohydrate, lipid,
      and apolipoprotein metabolisms with the future risk of amyotrophic lateral
      sclerosis (ALS). METHODS: In the Apolipoprotein-related MOrtality RISk study, we
      enrolled 636,132 men and women during 1985-1996 in Stockholm, Sweden, with
      measurements of serum glucose, total cholesterol, triglycerides, apolipoprotein B
      (apoB), and apolipoprotein A-I (apoA-I). Serum low-density lipoprotein
      cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were either
      directly measured or calculated from total cholesterol, triglycerides, and apoA
      I. The cohort was followed until the end of 2011. We used Cox models and mixed
      effects models to, first, estimate the associations between these biomarkers and
      ALS incidence and, second, to assess the changes of these biomarkers during the
      20 years before ALS diagnosis. RESULTS: One-unit increase of LDL-C (hazard ratio
      [HR] = 1.14; 95% confidence interval [CI] = 1.02-1.27), apoB (HR = 1.68; 95% CI =
      1.17-2.42), and apoB/apoA-I ratio (HR = 1.90; 95% CI = 1.29-2.78) was associated
      with a higher incidence of ALS. High glucose level (>=6.11mmol/L) was associated
      with a lower incidence (HR = 0.62; 95% CI = 0.42-0.93), whereas high LDL-C/HDL-C
      (>=3.50; HR = 1.50; 95% CI = 1.15-1.96) and high apoB/apoA-I (>=0.90 for men,
      >=0.8 for women; HR = 1.41; 95% CI = 1.04-1.90) ratios were associated with a
      higher incidence. During the 10 years before diagnosis, ALS patients had
      increasing levels of LDL-C, HDL-C, apoB, and apoA-I, whereas gradually decreasing
      levels of LDL-C/HDL-C and apoB/apoA-I ratios. INTERPRETATION: Alterations in the
      carbohydrate, lipid, and apolipoprotein metabolisms are associated with ALS risk
      and may serve as prodromal symptoms decades before ALS diagnosis. The imbalance
      between apoB and apoA-I as well as between LDL-C and HDL-C may be an etiological
      mechanism for ALS and needs to be further studied. Ann Neurol 2017;81:718-728.

PMID- 28437841
TI  - Characterizing the Evolution of Wide-Gauge Features in Stylopodial Limb Elements
      of Titanosauriform Sauropods via Geometric Morphometrics.
AB  - Wide-gauge posture of titanosauriform sauropods remains an enigmatic peculiarity
      among terrestrial vertebrates. Here, two-dimensional geometric morphometrics and
      thin plate splines analyses were used to quantitatively analyze shape differences
      among sauropodomorph humeri and femora to identify how these elements may differ
      according to body gauge. Results demonstrate that titanosauriforms generally
      possess proportionately gracile humeri in comparison to other sauropods, with
      relatively more medially oriented humeral heads and proximally located
      deltopectoral crests. Myological repercussions of these features demonstrate a
      relative sacrificing of muscular torque for forelimb abduction/adduction in
      exchange for minimization of necessary muscle contraction to generate the same
      degree of limb excursion. Regarding femora, titanosauriforms possess
      significantly broader femora mediolaterally than other sauropods, with
      comparatively proximomedially placed fourth trochanters. Canonical variates
      results also identify a trend for titanosauriform femora to present distal
      condyles that are more frequently perpendicular to the long axis of the shaft or
      beveled medially. All of these femoral shape characteristics are expressed to the
      greatest degree by titanosaurians. Myologically, mediolateral femoral broadening
      increases relative mechanical advantages for hind limb abductor and adductor
      musculature. This supports previous hypotheses that suggested titanosauriforms
      were capable of a greater degree of hind limb abduction and adduction. This
      capability may have been necessary to maintain dynamic stability during wide
      gauge locomotion over uneven terrain. Overall, our results corroborate previous
      qualitative assessments of wide-gauge attributes, afford new insights into
      statistically significant but obscure shape patterns, and add new clarity to
      aspects of the functional morphology of wide-gauge posture. Anat Rec, 300:1618
      1635, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28437842
TI  - Autoimmune-like chronic hepatitis induced by olmesartan.

PMID- 28437843
TI  - A Bayesian Belief Network Model Assessing the Risk to Wastewater Workers of
      Contracting Ebola Virus Disease During an Outbreak.
AB  - During an outbreak of Ebola virus disease (EVD), hospitals' connections to
      municipal wastewater systems may provide a path for patient waste bearing
      infectious viral particles to pass from the hospital into the wastewater
      treatment system, potentially posing risks to sewer and wastewater workers. To
      quantify these risks, we developed a Bayesian belief network model incorporating
      data on virus behavior and survival along with structural characteristics of
      hospitals and wastewater treatment systems. We applied the model to assess risks
      under several different scenarios of workers' exposure to wastewater for a
      wastewater system typical of a mid-sized U.S. city. The model calculates a median
      daily risk of developing EVD of approximately 6.1*10-12 (90% confidence interval:
      1.0*10-12 to 5.4*10-9 ; mean 1.8*10-6 ) when no prior exposure conditions are
      specified. Under a worst-case scenario in which a worker stationed in the sewer
      adjacent to the hospital accidentally ingests several drops (0.35 mL) of
      wastewater, median risk is 5.8*10-4 (90% CI: 8.8*10-7 to 9.5*10-2 ; mean 3.2*10-2
      ) . Disinfection of patient waste with peracetic acid for 15 minutes prior to
      flushing decreases the estimated median risk to 3.8*10-7 (90% CI: 4.1*10-9 to
      8.6*10-5 ; mean 2.9*10-5 ). The results suggest that requiring hospitals to
      disinfect EVD patient waste prior to flushing may be advisable. The modeling
      framework can provide insight into managing patient waste during future outbreaks
      of highly virulent infectious pathogens.

PMID- 28437844
TI  - Liver resection for hepatocellular carcinoma associated with hepatic vein
      invasion: A Japanese nationwide survey.
AB  - : Because of the rarity of hepatic vein tumor thrombus (HVTT) compared with
      portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma,
      little is known about this disease entity. The aim of this study was to evaluate
      the prognosis of each treatment modality for HVTT through an analysis of data
      collected in a Japanese nationwide survey. We analyzed data for 1,021 Child-Pugh
      A hepatocellular carcinoma patients with HVTT without inferior vena cava invasion
      registered between 2000 and 2007. Of these patients, 540 who underwent liver
      resection (LR) and 481 who received other treatments were compared. Propensity
      scores were calculated, and we successfully matched 223 patients (49.0% of the LR
      group). The median survival time in the LR group was 2.89 years longer than that
      in the non-LR group (4.47 versus 1.58 years, P < 0.001) and 1.61 years longer
      than that in the non-LR group (3.42 versus 1.81 years, P = 0.023) in a propensity
      score-matched cohort. After curative resection, median survival times were
      similar between patients with HVTT in the peripheral hepatic vein and those with
      HVTT in the major hepatic vein (4.85 versus 4.67 years, P = 0.974). In the LR
      group, the postoperative 90-day mortality rate was 3.4% (16 patients). In
      patients without PVTT, the median survival time was significantly better than
      that in patients with PVTT (5.67 versus 1.88 years, P < 0.001). CONCLUSION: LR is
      associated with a good prognosis in hepatocellular carcinoma patients with HVTT,
      especially in patients without PVTT. (Hepatology 2017;66:510-517).

PMID- 28437845
TI  - A small specific-sized hyaluronic acid ameliorates alcoholic liver disease by
      targeting a small RNA: New hope for therapy?

PMID- 28437846
TI  - Association Between Pain Sensitization and Disease Activity in Patients With
      Rheumatoid Arthritis: A Cross-Sectional Study.
AB  - OBJECTIVE: Pain sensitization may contribute to pain severity in rheumatoid
      arthritis (RA), impacting disease activity assessment. We examined whether pain
      processing mechanisms were associated with disease activity among RA patients
      with active disease. METHODS: The study included 139 subjects enrolled in the
      Central Pain in Rheumatoid Arthritis cohort. Subjects underwent quantitative
      sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at
      multiple sites, conditioned pain modulation, and temporal summation. RA disease
      activity was assessed using the Clinical Disease Activity Index (CDAI) and its
      components. We examined cross-sectional associations between QST measures and
      disease activity using linear regression. RESULTS: Low PPTs (high pain
      sensitization) at all sites were associated with high CDAI scores (P <= 0.03) and
      tender joint counts (P <= 0.002). Associations between PPTs and patient global
      assessments were also seen at most sites. High temporal summation at the forearm
      (also reflecting high pain sensitization) was significantly associated with high
      CDAI scores (P = 0.02), patient global assessment scores (P = 0.0006), evaluator
      global assessment scores (P = 0.01), and tender joint counts (P = 0.02).
      Conversely, conditioned pain modulation (a measure of descending inhibitory pain
      pathways) was associated only with tender joint count (P = 0.03). CONCLUSION:
      High pain sensitization is associated with elevations in disease activity
      measures. Longitudinal studies are underway to elucidate the cause-effect
      relationships between pain sensitization and inflammatory disease activity in RA.

PMID- 28437847
TI  - The impact of sample site and storage on thromboelastography values.

PMID- 28437848
TI  - Inferring network structure in non-normal and mixed discrete-continuous genomic
      data.
AB  - Inferring dependence structure through undirected graphs is crucial for
      uncovering the major modes of multivariate interaction among high-dimensional
      genomic markers that are potentially associated with cancer. Traditionally,
      conditional independence has been studied using sparse Gaussian graphical models
      for continuous data and sparse Ising models for discrete data. However, there are
      two clear situations when these approaches are inadequate. The first occurs when
      the data are continuous but display non-normal marginal behavior such as heavy
      tails or skewness, rendering an assumption of normality inappropriate. The second
      occurs when a part of the data is ordinal or discrete (e.g., presence or absence
      of a mutation) and the other part is continuous (e.g., expression levels of genes
      or proteins). In this case, the existing Bayesian approaches typically employ a
      latent variable framework for the discrete part that precludes inferring
      conditional independence among the data that are actually observed. The current
      article overcomes these two challenges in a unified framework using Gaussian
      scale mixtures. Our framework is able to handle continuous data that are not
      normal and data that are of mixed continuous and discrete nature, while still
      being able to infer a sparse conditional sign independence structure among the
      observed data. Extensive performance comparison in simulations with alternative
      techniques and an analysis of a real cancer genomics data set demonstrate the
      effectiveness of the proposed approach.

PMID- 28437849
TI  - Clinical significance of IgE in a large cohort of patients with moderate or
      severe chronic graft-versus-host disease.

PMID- 28437850
TI  - Public Perception of Uncertainties Within Climate Change Science.
AB  - Climate change is a complex, multifaceted problem involving various interacting
      systems and actors. Therefore, the intensities, locations, and timeframes of the
      consequences of climate change are hard to predict and cause uncertainties.
      Relatively little is known about how the public perceives this scientific
      uncertainty and how this relates to their concern about climate change. In this
      article, an online survey among 306 Swiss people is reported that investigated
      whether people differentiate between different types of uncertainty in climate
      change research. Also examined was the way in which the perception of uncertainty
      is related to people's concern about climate change, their trust in science,
      their knowledge about climate change, and their political attitude. The results
      of a principal component analysis showed that respondents differentiated between
      perceived ambiguity in climate research, measurement uncertainty, and uncertainty
      about the future impact of climate change. Using structural equation modeling, it
      was found that only perceived ambiguity was directly related to concern about
      climate change, whereas measurement uncertainty and future uncertainty were not.
      Trust in climate science was strongly associated with each type of uncertainty
      perception and was indirectly associated with concern about climate change. Also,
      more knowledge about climate change was related to less strong perceptions of
      each type of climate science uncertainty. Hence, it is suggested that to increase
      public concern about climate change, it may be especially important to consider
      the perceived ambiguity about climate research. Efforts that foster trust in
      climate science also appear highly worthwhile.

PMID- 28437851
TI  - Fexofenadine, a Putative In Vivo P-glycoprotein Probe, Fails to Predict Clearance
      of the Substrate Tacrolimus in Renal Recipients.
AB  - Whether the combined use of probe drugs for CYP3A4 and P-glycoprotein can clarify
      the relative contribution of these proteins to pharmacokinetic variability of a
      dual substrate like tacrolimus has never been assessed. Seventy renal recipients
      underwent simultaneous 8-h pharmacokinetic profiles for tacrolimus, the CYP3A4
      probe midazolam, and the putative P-glycoprotein probe fexofenadine. Patients
      were genotyped for polymorphisms in CYP3A5, CYP3A4, ABCB1, ABCC2 and SLCO2B1, 
      1B1, and 1B3. Carriers of the ABCB1 2677G>A polymorphism displayed lower
      fexofenadine Cmax (-66%; P = 0.012) and a trend toward higher clearance (+157%; P
      = 0.078). Predictors of tacrolimus clearance were CYP3A5 genotype, midazolam
      clearance, hematocrit, weight, and age (R2 = 0.61). Fexofenadine pharmacokinetic
      parameters were not predictive of tacrolimus clearance. In conclusion,
      fexofenadine pharmacokinetics varied considerably between renal recipients but
      most of this variability remained unexplained, with only minor effects of genetic
      polymorphisms. Fexofenadine cannot be used to assess in vivo CYP3A4-P
      glycoprotein interplay in tacrolimus-treated renal recipients.

PMID- 28437853
TI  - Inhibition of TGF-beta signaling promotes expansion of human epidermal
      keratinocytes in feeder cell co-culture.
AB  - Cultured epidermal autografts have been used worldwide since 1981 for patients
      with extensive third-degree burn wounds and limited skin donor sites. Despite
      significant progress in techniques toward improving clinical outcome of skin
      grafts, the long in vitro preparation time of cultured autografts has remained a
      major factor limiting its widespread use. Here, we show that pharmacological
      inhibition of TGF-beta signaling promotes the expansion of human epidermal
      keratinocytes (HEKs) with high proliferative potential in co-cultures with both
      murine 3T3-J2 cells and human feeder cells, including dermal fibroblasts and
      preadipocytes. In contrast, TGF-beta signaling inhibition does not enhance the
      growth of HEKs in a serum- and feeder-free condition, an alternative approach to
      propagate HEKs for subsequent autograft production. Our results have important
      implications for the use of TGF-beta signaling inhibition as a viable therapeutic
      strategy for improving Green's methodology and for more efficient production of
      customized skin autografts with human feeder cells.

PMID- 28437854
TI  - Is there sufficient evidence for a causal association between antiretroviral
      therapy and diabetes in HIV-infected patients? A meta-analysis.
AB  - The association of antiretroviral therapy (ART) with diabetes is inconsistent and
      varies widely across primary epidemiological studies. A comprehensive and more
      precise estimate of this association is fundamental to establishing a plausible
      causal link between ART and diabetes. We identified epidemiological studies that
      compared mean fasting plasma glucose (FPG) concentrations and proportions of
      diabetes and metabolic syndrome between HIV-infected patients naive and exposed
      to ART. Mean difference in FPG concentrations and odds ratios of diabetes and
      metabolic syndrome were pooled using random-effects meta-analyses. Data on 20 178
      participants from 41 observational studies were included in the meta-analyses.
      Mean FPG concentrations (Pooled mean difference: 4.66 mg/dL; 95% confidence
      interval [CI], 2.52 to 6.80; 24 studies) and the odds of diabetes (Pooled odds
      ratios: 3.85; 95% CI, 2.93 to 5.07; 10 studies) and metabolic syndrome (Pooled
      odds ratios: 1.45; 95% CI, 1.03 to 2.03; 18 studies) were significantly higher
      among ART-exposed patients, compared to their naive counterparts. ART was also
      associated with significant increases in FPG levels in studies with mean ART
      duration >=18 months (Pooled mean difference: 4.97 mg/dL; 95% CI, 3.10 to 6.84;
      14 studies), but not in studies with mean ART duration <18 months (Pooled mean
      difference: 4.40 mg/dL, 95% CI, -0.59 to 9.38; 7 studies). ART may potentially be
      the single most consistent determinant of diabetes in people living with HIV
      worldwide. However, given the preponderance of cross-sectional studies in the
      meta-analysis, the association between ART and diabetes cannot be interpreted as
      cause and effect.

PMID- 28437852
TI  - A diagnostic microdosing approach to investigate platinum sensitivity in non
      small cell lung cancer.
AB  - The platinum-based drugs cisplatin, carboplatin and oxaliplatin are often used
      for chemotherapy, but drug resistance is common. The prediction of resistance to
      these drugs via genomics is a challenging problem since hundreds of genes are
      involved. A possible alternative is to use mass spectrometry to determine the
      propensity for cells to form drug-DNA adducts-the pharmacodynamic drug-target
      complex for this class of drugs. The feasibility of predictive diagnostic
      microdosing was assessed in non-small cell lung cancer (NSCLC) cell culture and a
      pilot clinical trial. Accelerator mass spectrometry (AMS) was used to quantify
      [14 C]carboplatin-DNA monoadduct levels in the cell lines induced by microdoses
      and therapeutic doses of carboplatin, followed by correlation with carboplatin
      IC50 values for each cell line. The adduct levels in cell culture experiments
      were linearly proportional to dose (R2  = 0.95, p < 0.0001) and correlated with
      IC50 across all cell lines for microdose and therapeutically relevant carboplatin
      concentrations (p = 0.02 and p = 0.01, respectively). A pilot microdosing
      clinical trial was conducted to define protocols and gather preliminary data.
      Plasma pharmacokinetics (PK) and [14 C]carboplatin-DNA adducts in white blood
      cells and tumor tissues from six NSCLC patients were quantified via AMS. The
      blood plasma half-life of [14 C]carboplatin administered as a microdose was
      consistent with the known PK of therapeutic dosing. The optimal [14 C]carboplatin
      formulation for the microdose was 107 dpm/kg of body weight and 1% of the
      therapeutic dose for the total mass of carboplatin. No microdose-associated
      toxicity was observed in the patients. Additional accruals are required to
      significantly correlate adduct levels with response.

PMID- 28437855
TI  - Mild fetal cerebral ventriculomegaly: prevalence, characteristics, and utility of
      ancillary testing in cases presenting to a tertiary referral center.
AB  - OBJECTIVE: Ventriculomegaly is the most common fetal brain anomaly identified
      during prenatal anatomy ultrasound. The aim of our study was to characterize
      cases of mild ventriculomegaly and investigate the utility of ancillary tests.
      METHOD: We reviewed 121 cases of mild ventriculomegaly, defined as lateral
      ventricle diameter of 10 to 15 mm. Characteristics of the ventricular dilation as
      well as each pregnancy were investigated. Ancillary tests performed included
      follow-up magnetic resonance imaging (MRI), chromosomal abnormality testing, and
      maternal serologic infection screening. The utility of each test was analyzed.
      RESULTS: We identified 56 cases of isolated and 65 cases of complex
      ventriculomegaly. Seventy-two (59.5%) were unilateral, and 49 (40.5%) were
      bilateral, with a mean gestational age at diagnosis of 24.5 weeks. MRI provided
      additional information in 3/24 (12.5%) cases of isolated ventriculomegaly
      compared with 18/23 (78.2%) cases of complex ventriculomegaly. Chromosomal
      abnormality testing identified 4/9 (44.4%) genetic abnormalities compared with
      8/30 (26.7%) in cases of isolated and complex mild ventriculomegaly,
      respectively. Finally, maternal serology infection screening was negative in all
      cases. CONCLUSION: Ancillary testing is useful in isolated mild ventriculomegaly.
      Follow-up MRI and chromosome abnormality testing specifically provided clinically
      useful information. Although there were no cases of maternal infection, screening
      may be an important component in management. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28437856
TI  - Microstructure Variations in the Soft-Hard Tissue Junction of the Human Anterior
      Cruciate Ligament.
AB  - The role of the sub-bundles in the anterior cruciate ligament (ACL) has been
      defined, such that the anterior-medial bundle directly resists anterior tibial
      translation while the posterior lateral bundle is involved in rotational
      stability. With regards to this biomechanical function, much of the previous work
      on bundle-specific morphology has been carried out on the macroscale, with much
      less attention given to the micro-to-ultrastructural scalar levels. This is
      especially true of the enthesis and its microstructure, a biomechanically
      significant region that has been largely neglected in the published literature
      dealing with ACL sub-bundle anatomy. In this study, the human ACL tibial enthesis
      was investigated at multiple scalar levels using differential interference
      contrast and scanning electron microscopies with the aim of determining whether
      the sub-bundle ligament structure, and its known macroscale function, is
      consistent with its micro-architecture at the ligament-bone junction. The
      investigation found that different ligament insertion morphologies exist between
      the two bundles, where the AM bundle has more intense interdigitation with the
      bone matrix than that of the PL bundle. The results suggest that such structure
      function relationships, especially across scalar-levels, provide new insight into
      the significance of the sub-bundle anatomy of the ACL. Anat Rec, 300:1547-1559,
      2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28437858
TI  - Assessment of preoperative liver function based on indocyanine green clearance.

PMID- 28437857
TI  - Influence of inflammation and nitric oxide upon platelet aggregation following
      deposition of diesel exhaust particles in the airways.
AB  - BACKGROUND AND PURPOSE: Exposure to nanoparticulate pollution has been implicated
      in platelet-driven thrombotic events such as myocardial infarction. Inflammation
      and impairment of NO bioavailability have been proposed as potential causative
      mechanisms. It is unclear, however, whether airways exposure to combustion
      derived nanoparticles such as diesel exhaust particles (DEP) or carbon black (CB)
      can augment platelet aggregation in vivo and the underlying mechanisms remain
      undefined. We aimed to investigate the effects of acute lung exposure to DEP and
      CB on platelet activation and the associated role of inflammation and endothelial
      derived NO. EXPERIMENTAL APPROACH: DEP and CB were intratracheally instilled into
      wild-type (WT) and eNOS-/- mice and platelet aggregation was assessed in vivo
      using an established model of radio-labelled platelet thromboembolism. The
      underlying mechanisms were investigated by measuring inflammatory markers, NO
      metabolites and light transmission aggregometry. KEY RESULTS: Platelet
      aggregation in vivo was significantly enhanced in WT and eNOS-/- mice following
      acute airways exposure to DEP but not CB. CB exposure, but not DEP, was
      associated with significant increases in pulmonary neutrophils and IL-6 levels in
      the bronchoalveolar lavage fluid and plasma of WT mice. Neither DEP nor CB
      affected plasma nitrate/nitrite concentration and DEP-induced human platelet
      aggregation was inhibited by an NO donor. CONCLUSIONS AND IMPLICATIONS: Pulmonary
      exposure to DEP and subsequent platelet activation may contribute to the reports
      of increased cardiovascular risk, associated with exposure to airborne pollution,
      independent of its effects on inflammation or NO bioavailability.

PMID- 28437859
TI  - Multiple sclerosis broke my heart.
AB  - We report 5 cases of acute heart failure (AHF) related to multiple sclerosis (MS)
      relapses. AHF was inaugural in 3 patients, always preceded or accompanied by
      signs of brainstem dysfunction; it was severe, requiring intensive care
      management. Echocardiography showed left ventricular hypokinesis. No other cause
      of AHF has been found. All patients showed a new medullary lesion on brain
      magnetic resonance imaging. All had rapid and complete recovery of ventricular
      function after intravenous corticosteroids. We concluded that the cases represent
      a takotsubo phenomenon. Physicians should be aware of rare cases of takotsubo
      cardiomyopathy in MS relapses. Ann Neurol 2017;81:754-758.

PMID- 28437861
TI  - Three-Stage Decision-Making Model under Restricted Conditions for Emergency
      Response to Ships Not under Control.
AB  - A ship that is not under control (NUC) is a typical incident that poses serious
      problems when in confined waters close to shore. The emergency response to NUC
      ships is to select the best risk control options, which is a challenge in
      restricted conditions (e.g., time limitation, resource constraint, and
      information asymmetry), particularly in inland waterway transportation. To enable
      a quick and effective response, this article develops a three-stage decision
      making framework for NUC ship handling. The core of this method is (1) to propose
      feasible options for each involved entity (e.g., maritime safety administration,
      NUC ship, and ships passing by) under resource constraint in the first stage, (2)
      to select the most feasible options by comparing the similarity of the new case
      and existing cases in the second stage, and (3) to make decisions considering the
      cooperation between the involved organizations by using a developed Bayesian
      network in the third stage. Consequently, this work provides a useful tool to
      achieve well-organized management of NUC ships.

PMID- 28437860
TI  - Chronic inhibition of fatty acid amide hydrolase by URB597 produces differential
      effects on cardiac performance in normotensive and hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Fatty acid amide hydrolase (FAAH) inhibitors are
      postulated to possess anti-hypertensive potential, because their acute injection
      decreases BP in spontaneously hypertensive rats (SHR), partly through
      normalization of cardiac contractile function. Here, we examined whether the
      potential hypotensive effect of chronic FAAH inhibition by URB597 in hypertensive
      rats correlated with changes in cardiac performance. EXPERIMENTAL APPROACH:
      Experiments were performed using perfused hearts and left atria isolated from 8-
      to 10-week-old SHR, age-matched deoxycorticosterone acetate (DOCA)-salt rats and
      normotensive controls chronically treated with URB597 (1 mg.kg-1 ) or vehicle.
      KEY RESULTS: URB597 decreased BP only in the DOCA-salt rats, along with a
      reduction of ventricular hypertrophy and diastolic stiffness, determined in
      hypertension. We also observed normalization of the negative inotropic atrial
      response to the cannabinoid receptor agonist CP55940. In the SHR model, URB597
      normalized (atria) and enhanced (hearts) the positive ino- and chronotropic
      effects of the beta-adrenoceptor agonist isoprenaline respectively. Ventricular
      CB1 and CB2 receptor expression was decreased only in the DOCA-salt model,
      whereas FAAH expression was reduced in both models. URB597 caused translocation
      of CB1 receptor immunoreactivity to the intercalated discs in the hearts of SHR.
      URB597 increased cardiac diastolic stiffness and modified the ino- and lusitropic
      effects of isoprenaline in normotensive rats. CONCLUSION AND IMPLICATIONS:
      Hypotensive effect of chronic FAAH inhibition depend on the model of hypertension
      and partly correlate with improved cardiac performance. In normotensive rats,
      chronic FAAH inhibition produced several side-effects. Thus, the therapeutic
      potential of these agents should be interpreted cautiously.

PMID- 28437862
TI  - Lewis P. Rowland, MD: 1925-2017.

PMID- 28437864
TI  - Linear-No-Threshold Default Assumptions are Unwarranted for Cytotoxic Endpoints
      Independently Triggered by Ultrasensitive Molecular Switches.
AB  - Crump's response in this issue to my critique of linear-no-threshold (LNT)
      default assumptions for noncancer and nongenotoxic cancer risks (Risk Analysis
      2016; 36(3):589-604) is rebutted herein. Crump maintains that distinguishing
      between a low-dose linear dose response and a threshold dose response on the
      basis of dose-response data is impossible even for endpoints involving increased
      cytotoxicity. My rebuttal relies on descriptions and specific illustrations of
      two well-characterized ultrasensitive molecular switches that govern two key
      cytoprotective responses to cellular stress-heat shock response and antioxidant
      response element activation, respectively-each of which serve to suppress stress
      induced apoptotic cell death unless overwhelmed. Because detailed dose-response
      data for each endpoint is shown to be J- or inverted-J-shaped with high
      confidence, and because independent pathways can explain background rates of
      apoptosis, LNT assumptions for this cytotoxic endpoint are unwarranted, at least
      in some cases and perhaps generally.

PMID- 28437863
TI  - Sirtuin 3 acts as a negative regulator of autophagy dictating hepatocyte
      susceptibility to lipotoxicity.
AB  - : Lipotoxicity induced by saturated fatty acids (SFAs) plays a central role in
      the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, the exact
      mechanisms remain to be fully elucidated. Sirtuin 3 (SIRT3) is a nicotinamide
      adenine dinucleotide-dependent deacetylase located primarily inside mitochondria.
      In this study, we demonstrated that an SFA-rich high-fat diet (HFD) was more
      detrimental to the liver than an isocaloric unsaturated HFD rich in fatty acids.
      Unexpectedly, SIRT3 expression and activity were significantly elevated in the
      livers of mice exposed to the SFA-rich HFD. Using cultured HepG2 and AML-12
      hepatocytes, we demonstrated that unlike monounsaturated fatty acids, SFAs up
      regulate SIRT3 expression and activity. SIRT3 overexpression renders both the
      liver and hepatocytes susceptible to palmitate-induced cell death, which can be
      alleviated by SIRT3 small interfering RNA (siRNA) transfection. In contrast,
      SIRT3 suppression protects hepatocytes from palmitate cytotoxicity. Further
      studies revealed that SIRT3 acts as a negative regulator of autophagy, thereby
      enhancing the susceptibility of hepatocytes to SFA-induced cytotoxicity.
      Mechanistic investigations revealed that SIRT3 overexpression causes manganese
      superoxide dismutase deacetylation and activation, which depleted intracellular
      superoxide contents, leading to adenosine monophosphate-activated protein kinase
      (AMPK) inhibition and mammalian target of rapamycin C1 activation, resulting in
      autophagy suppression. In contrast, SIRT3 siRNA gene silencing enhanced autophagy
      flux. A similar result was observed in the liver tissue of SIRT3 knockout mice.
      CONCLUSION: Our data indicate that SIRT3 is a negative regulator of autophagy
      whose activation by SFAs contributes to lipotoxicity in hepatocytes and suggest
      that restraining SIRT3 overactivation can be a potential therapeutic choice for
      the treatment of NAFLD as well as other metabolic disorders, with lipotoxicity
      being the principal pathomechanism. (Hepatology 2017;66:936-952).

PMID- 28437866
TI  - Alpha1-antitrypsin deficiency and c-JUN.

PMID- 28437867
TI  - Robustness Assessment of Urban Road Network with Consideration of Multiple Hazard
      Events.
AB  - Robustness measures a system's ability of being insensitive to disturbances.
      Previous studies assessed the robustness of transportation networks to a single
      disturbance without considering simultaneously happening multiple events. The
      purpose of this article is to address this problem and propose a new framework to
      assess the robustness of an urban transportation network. The framework consists
      of two layers. The upper layer is to define the robustness index based on the
      impact evaluation in different scenarios obtained from the lower layer, whereas
      the lower layer is to evaluate the performance of each hypothetical disrupted
      road network given by the upper layer. The upper layer has two varieties, that
      is, robustness against random failure and robustness against intentional attacks.
      This robustness measurement framework is validated by application to a real-world
      urban road network in Hong Kong. The results show that the robustness of a
      transport network with consideration of multiple events is quite different from
      and more comprehensive than that with consideration of only a single disruption.
      We also propose a Monte Carlo method and a heuristic algorithm to handle
      different scenarios with multiple hazard events, which is proved to be quite
      efficient. This methodology can also be applied to conduct risk analysis of other
      systems where multiple failures or disruptions exist.

PMID- 28437865
TI  - A novel role of astrocyte elevated gene-1 (AEG-1) in regulating nonalcoholic
      steatohepatitis (NASH).
AB  - : Nonalcoholic steatohepatitis (NASH) is the most prevalent cause of chronic
      liver disease in the Western world. However, an optimum therapy for NASH is yet
      to be established, mandating more in-depth investigation into the molecular
      pathogenesis of NASH to identify novel regulatory molecules and develop targeted
      therapies. Here, we unravel a unique function of astrocyte elevated gene-1(AEG
      1)/metadherin in NASH using a transgenic mouse with hepatocyte-specific
      overexpression of AEG-1 (Alb/AEG-1) and a conditional hepatocyte-specific AEG-1
      knockout mouse (AEG-1DeltaHEP ). Alb/AEG-1 mice developed spontaneous NASH
      whereas AEG-1DeltaHEP mice were protected from high-fat diet (HFD)-induced NASH.
      Intriguingly, AEG-1 overexpression was observed in livers of NASH patients and
      wild-type (WT) mice that developed steatosis upon feeding HFD. In-depth molecular
      analysis unraveled that inhibition of peroxisome proliferator-activated receptor
      alpha activity resulting in decreased fatty acid beta-oxidation, augmentation of
      translation of fatty acid synthase resulting in de novo lipogenesis, and
      increased nuclear factor kappa B-mediated inflammation act in concert to mediate
      AEG-1-induced NASH. Therapeutically, hepatocyte-specific nanoparticle-delivered
      AEG-1 small interfering RNA provided marked protection from HFD-induced NASH in
      WT mice. CONCLUSION: AEG-1 might be a key molecule regulating initiation and
      progression of NASH. AEG-1 inhibitory strategies might be developed as a
      potential therapeutic intervention in NASH patients. (Hepatology 2017;66:466
      480).

PMID- 28437868
TI  - Early mortality and overall survival of acute myeloid leukemia based on facility
      type.
AB  - Cancer health disparities may exist based on the facility type. We aimed to
      determine the association between the academic status of centers and outcomes of
      patients with acute myeloid leukemia (AML). Using the National Cancer Data Base,
      we compared 1-month mortality and long-term overall survival (OS) of 60 738
      patients with AML, who received first course treatment between 2003 and 2011 at
      academic or nonacademic centers (community cancer program, comprehensive
      community cancer program, and others). Multivariate analysis was done using
      logistic regression for one-month mortality and Cox regression with backward
      elimination approach for OS. Patients treated at academic centers differed from
      those at nonacademic centers in that they were younger with a median age of 62
      versus 70 years (P < .0001), more often an ethnic minority (P < .0001), had lower
      education level (P = .005), lower co-morbidity score (P < .0001), a different
      income (P < .0001), and insurance profile (P < .0001), and more often received
      chemotherapy (P < .0001) and transplant (P < .0001). Receipt of care at
      nonacademic centers was associated with worse 1-month mortality (29% vs. 16%, P <
      .0001) and 5-year OS (15% vs. 25%; P < .0001). After adjusting for prognostic
      covariates, the 1-month mortality (odds ratio, 1.52; 95% confidence interval, CI
      1.46-1.59; P < .0001) and OS were significantly worse in nonacademic centers,
      compared to academic centers. Our large database study suggests that the receipt
      of initial therapy at academic centers is associated with lower 1-month mortality
      and higher long-term OS. Investigation of the underlying reasons may allow
      reducing this disparity.

PMID- 28437869
TI  - Risk Modeling of Interdependent Complex Systems of Systems: Theory and Practice.
AB  - The emergence of the complexity characterizing our systems of systems (SoS)
      requires a reevaluation of the way we model, assess, manage, communicate, and
      analyze the risk thereto. Current models for risk analysis of emergent complex
      SoS are insufficient because too often they rely on the same risk functions and
      models used for single systems. These models commonly fail to incorporate the
      complexity derived from the networks of interdependencies and interconnectedness
      (I-I) characterizing SoS. There is a need to reevaluate currently practiced risk
      analysis to respond to this reality by examining, and thus comprehending, what
      makes emergent SoS complex. The key to evaluating the risk to SoS lies in
      understanding the genesis of characterizing I-I of systems manifested through
      shared states and other essential entities within and among the systems that
      constitute SoS. The term "essential entities" includes shared decisions,
      resources, functions, policies, decisionmakers, stakeholders, organizational
      setups, and others. This undertaking can be accomplished by building on state
      space theory, which is fundamental to systems engineering and process control.
      This article presents a theoretical and analytical framework for modeling the
      risk to SoS with two case studies performed with the MITRE Corporation and
      demonstrates the pivotal contributions made by shared states and other essential
      entities to modeling and analysis of the risk to complex SoS. A third case study
      highlights the multifarious representations of SoS, which require harmonizing the
      risk analysis process currently applied to single systems when applied to complex
      SoS.

PMID- 28437870
TI  - Assessing the Likelihood and Magnitude of a Population Health Benefit Following
      the Market Introduction of a Modified-Risk Tobacco Product: Enhancements to the
      Dynamic Population Modeler, DPM(+1).
AB  - Researchers and those responsible for evaluating and implementing policies
      intended to reduce population harm must assess the potential for both intended
      and unintended consequences associated with those policies. Such assessments
      should be based on the combined dimensions of magnitude, and thus likelihood, of
      shifts in exposure patterns needed to produce a population benefit or harm, and
      magnitude of the expected population benefit or harm. In response to this
      assessment need, we provide a conceptual description of the dynamic population
      modeler, DPM(+1), as well as illustrative analyses that estimate the effects on
      all-cause mortality, life expectancy, and quality of life-adjusted life
      expectancy if exposure patterns in the population shift from a higher risk
      product (e.g., cigarettes) to a lower, or modified, risk tobacco product (MRTP)
      in specified ways. Estimates from these analyses indicate that, within a single
      birth cohort, switching completely from cigarette smoking to MRTP use is more
      likely to lead to a population-level survival benefit than initiating tobacco use
      with an MRTP instead of cigarettes. This is because tobacco initiation rarely
      occurs beyond young adulthood, whereas continuing smokers exist in all subsequent
      age categories, leading to a greater cumulative effect. In addition, complete
      switching to MRTP use among a small proportion of smokers in each age category
      offsets the survival deficit caused by unintended shifts in exposure patterns,
      such as MRTP initiation among never tobacco users followed by transitioning to
      cigarette smoking and/or cigarette smokers switching to MRTP use instead of
      quitting.

PMID- 28437871
TI  - Reply.

PMID- 28437872
TI  - Low-level viremia in hepatitis b patients on antiviral treatment: Can we ignore
      it?

PMID- 28437874
TI  - Reply.

PMID- 28437873
TI  - High prevalence of monoclonal gammopathy among patients with warm autoimmune
      hemolytic anemia.

PMID- 28437875
TI  - Heterogeneity of neutrophil spontaneous death.

PMID- 28437876
TI  - Prognostic Significance of Resection Degree in Skull Base Chordoma: A Systematic
      Review and Meta-Analysis.

PMID- 28437877
TI  - In Reply to "Prognostic Significance of Resection Degree in Skull Base Chordoma:
      A Systematic Review and Meta-Analysis".

PMID- 28437878
TI  - Perineural Spread or Neural Tropism? Discussion of a Paper and Description of an
      Unusual Case of Cervical Intradural Extramedullary Dumbbell Metastasis from Renal
      Cell Carcinoma.

PMID- 28437879
TI  - In Reply to "Perineural Spread or Neural Tropism? Discussion of a Paper and
      Description of an Unusual Case of Cervical Intradural Extramedullary Dumbbell
      Metastasis from Renal Cell Carcinoma".

PMID- 28437880
TI  - New Oral Anticoagulants and Pituitary Apoplexy.

PMID- 28437881
TI  - In Reply to "New Oral Anticoagulants and Pituitary Apoplexy".

PMID- 28437882
TI  - Intracranial Pressure Monitoring in Traumatic Brain Injury.

PMID- 28437883
TI  - In Reply to "Intracranial Pressure Monitoring in Traumatic Brain Injury".

PMID- 28437884
TI  - Regulatory role of miR-211-5p in hepatocellular carcinoma metastasis by targeting
      ZEB2.
AB  - Hepatocellular carcinoma (HCC) is the most common type of cancer and the rapid
      tumor growth, drug resistance and metastasis are the major problems for HCC
      therapy. MicroRNAs (miRNAs) involve in various cell biological processes in HCC.
      ZEB2 plays crucial roles in HCC progression. ZEB2 is regulated by some identified
      miRNAs, but there needs to find new miRNAs regulating ZEB2 expression for better
      understanding the molecular mechanism of HCC. In the present study, ZEB2 was
      identified as a direct target of miR-211-5p, which was a potential oncogene in
      cancer. We found that miR-211-5p levels in HCC tissues were lower than the
      compared normal tissues. ZEB2 expression was higher in HCC tissues and was
      negatively related to miR-211-5p levels. Overexpression of miR-211-5p in human
      HCC cell lines (HepG2 and 7721) caused the delay of cell proliferation, apoptosis
      and drug sensitivity. Summarily, our study demonstrates that miR-211-5p may play
      a suppressing role in HCC by inhibiting ZEB2 expression.

PMID- 28437885
TI  - Sesquiterpenes evaluation on Schistosoma mansoni: Survival, excretory system and
      membrane integrity.
AB  - The main challenge in schistosomiasis control has been the emergence of drug
      resistant parasites. Since the 1970's, praziquantel (PZQ) is the single drug for
      treatment. This fact highlights the importance to research news chemotherapeutic
      agents. In the last years, S. mansoni excretory system and tegument have been
      major targets for drug development. The purpose of this study was to evaluate the
      effect of sesquiterpenes, alpha-humulene and trans-caryophyllene on S. mansoni
      survival, excretory system and membrane integrity, after in vitro exposure. The
      in vitro studies, showed that sesquiterpenes reduced egg production and motor
      activity of worms at sublethal concentrations, and caused death in a
      concentration-dependent manner (100 and 200MUg/mL). Tegumental analysis by
      Scanning Electron Microscopy (SEM), showed tegument damage. Additionally, it was
      possible to observe lesions, evidenced by intense marking trough Hoechst probe,
      in the tegument and suckers of worms exposed to 200MUg/mL. In this study, we also
      showed that resorufin is only capable of identifying the interaction of
      sesquiterpenes in males excretory system, Pgp expression and inferring that
      females are more tolerant to treatments. Thus, the present study results
      contribute to an understanding of alpha-humulene and trans-caryophyllene effect
      over these targets, contributing for the development of schistosomicidal drugs.

PMID- 28437886
TI  - Activation of imidazoline I1 receptor by moxonidine regulates the progression of
      liver fibrosis in the Nrf2-dependent pathway.
AB  - Imidazoline I1 receptor (I1R) has been recognized as a promising target in the
      treatment of many diseases, but little is known about its function in liver
      fibrogenesis. This study aimed to investigate the effect of I1R activation on the
      development and progression of liver fibrosis. The results showed that I1R
      expression was decreased in the livers of both patients and mice with liver
      fibrosis, and in TGF-beta-treated hepatic stellate cells (HSCs). Activation of
      I1R by moxonidine (MOX) significantly inhibited the progression of liver fibrosis
      in carbon tetrachloride-induced mice and attenuated the activation of HSCs and
      kupffer cells. MOX also suppressed the activation of TLR4/NF-kappaB and TGF
      beta/Smad signaling, however, knockdown of I1R abrogated the inhibitory effects
      of MOX. Additionally, MOX activated Nrf2 signaling in vivo and in vitro, but
      knockout or knockdown of Nrf2 ameliorated the anti-inflammatory and anti-fibrotic
      effects of MOX. Taken together, activation of I1R negatively regulates the
      progression of liver fibrosis in the Nrf2-dependent pathway, which suggests that
      specifically targeting I1R may be a potential therapeutic strategy for the
      treatment of liver fibrosis.

PMID- 28437887
TI  - Influence of sinomenine upon mesenchymal stem cells in osteoclastogenesis.
AB  - With the advent of aging, the morbidity rates of such diseases as osteoarthritis,
      rheumatoid arthritis, and osteoporosis has witnessed a significant increase. As a
      common rattan drug, sinomenine (SIN) has been widely applied for the treatment of
      various arthritic diseases in traditional Chinese medicine (TCM) clinics. Given
      that SIN has been reported to inhibit the expression of Prostaglandin E2 (PGE2)
      in several types of cells, in this study, the influence of SIN treatment on PGE2
      expression in mesenchymal stem cells (MSCs), thereby changing the osteoprotegerin
      (OPG) receptor/activator for the nuclear factor-kappa B ligand (RANKL) ratio, was
      investigated. Our results showed that, when compared with the untreated cells,
      treatment with 0.25mM SIN can down-regulate the mRNA and protein expression
      levels of the Prostaglandin E synthase 3 (PTGES3) or PGE2 and RANKL, while the
      OPG was up-regulated. After being cultured with SIN treated MSC-conditioned
      medium (stMSC-CM), the amount of TRAP-positive multinucleated osteoclasts
      differentiated from RAW264.7 cells was reduced. Also, the expression levels of
      specific markers for active osteoclasts were decreased when incubated with stMSC
      CM. Moreover, these changes were able to be recovered when the exogenous RANKL
      was added to the MSC-CM culture. This indicates that the increased OPG/RANKL
      ratio can reduce the osteoclastogenesis of RAW264.7 cells. Our results
      demonstrated that SIN has an inhibitory effect on osteoclast differentiation
      through mechanisms involving the inhibition of the PGE2-induced OPG/RANKL ratio.
      SIN can also serve as a proinflammatory mediator to regulate the MSC
      immunosuppressive effects. Our findings suggest that SIN can be useful for the
      treatment of bone diseases associated with over-activity of osteoclasts.

PMID- 28437888
TI  - Protective effects of tranilast on experimental colitis in rats.
AB  - The present study aimed to verify the efficacy of tranilast (TL) for treating
      inflammatory bowel disease (IBD) with the use of an experimental colitis model.
      The experimental colitis model was prepared by intrarectal instillation of 2,4,6
      trinitrobenzenesulfonic acid (TNBS; 40mg/kg) dissolved in water containing 25%
      ethanol. The pharmacological effects of TL after repeated oral administration
      were evaluated by biomarker and histological analyses, and the pharmacokinetic
      behavior of TL was also examined after single oral administration. The
      intrarectal instillation of TNBS solution caused colitis, as evidenced by ca. 2.2
      , 5-, and 3-fold increases in myeloperoxidase (MPO) activity, infiltrated cell
      numbers, and the thickness of the submucosa in the colon, respectively. However,
      orally-taken TL (10mg/kg, twice a day for 9days) led to a 92% reduction in the
      increase of the MPO level by TNBS enema, and cellular infiltration and thickened
      submucosa in the experimental colitis model tended to also be suppressed by
      repeated oral administration of TL. The oral bioavailability of TL in TNBS
      treated rats was calculated to be as low as ca. 6.5%, and the poor oral
      absorption of TL may be a limitation of the treatment for IBD. TL could attenuate
      TNBS-induced colitis on the basis of the obtained results, and the anti
      inflammatory effects would have clinical relevance to the therapeutic outcomes of
      TL in IBD patients. Although further improvement in the oral bioavailability of
      TL might be required for better pharmacological outcomes, TL would be an
      efficacious agent for treating IBD.

PMID- 28437889
TI  - Safety of sucrose esters from Physalis peruviana L. in a 28-day repeated-dose
      study in mice.
AB  - Although extracts and consumed foods from Physalis species contain sucrose esters
      from their glandular trichomes, there is no experimental data available on their
      toxicological effects. As peruvioses A and B isolated from Physalis peruviana L.
      calyces have proved to be effective anti-inflammatory and immunomodulatory
      compounds, this work aimed to investigate their sub-acute toxicity study and
      genotoxicity. For this, CD-1(ICR) mice were treated intraperitoneally with
      peruvioses at doses of 2.5, 5, and 10mg/kg/day for 28 consecutive days, to
      simulate therapeutic and over-therapeutic dosage levels. At the end of the
      treatment, animals were sacrificed and their organs weighted, and blood and
      tissue samples were collected. Toxicological endpoints included clinical signs;
      food consumption; body and organ weights; hematological and biochemical
      parameters; as well as macroscopic and microscopic examination of tissues. The
      results showed no significant differences between treated animals and control
      group at macroscopic, histological, molecular, and biochemical levels. In
      addition, a combination of mammalian erythrocyte micronucleus test, comet assay
      in peripheral blood cells, and Ames test, did not reveal genotoxic effects
      induced by peruvioses. Taken together, our data suggests that peruvioses A and B
      can be safely employed to treat inflammatory diseases.

PMID- 28437890
TI  - Does propolis have any effect on non-alcoholic fatty liver disease?
AB  - The aim of this study was to evaluate the therapeutic effect of propolis on non
      alcoholic fatty liver disease (NAFLD) in rats. The rats were randomly divided
      into 3 groups of 10 as the NAFLD, NAFLD+100 and NAFLD+200 groups. The rats were
      fed with a fatty diet (25g/kg/day) to provoke NAFLD. Then after the formation of
      fatty liver, a standard diet (SD) (25g/kg/day) was given to the NAFLD group and
      the other two groups were fed with SD and 100mg/kg (NAFLD+100 Group) or 200mg/kg
      propolis (NAFLD+200 Group) for two weeks. At the end of two weeks the animals
      were sacrificed. Blood and tissue samples were taken for biochemical and
      histopathological evaluations. The propolis-treated groups had better results in
      serum lipids (total cholesterol, non-HDL cholesterol, triglyceride), ALT, and ALP
      values. When compared with the NAFLD group, IL-6 and TNF-alpha values decreased
      in the NAFLD+100 and NAFLD+200 groups. The administration of propolis to the rats
      significantly reduced serum and tissue MDA and GPX values and increased SH in
      serum when compared with the NAFLD group. No difference was determined between
      the groups treated with two different doses of propolis in respect of biochemical
      values. When the mean histological scores of the groups were compared,
      statistically significant differences were found between the NAFLD group and the
      propolis-treated groups. No difference was determined between the groups treated
      with the two different doses of propolis in respect of histopathological results.
      Propolis had positive effects on histopathological and biochemical parameters of
      NAFLD and these effects were related to the anti-oxidant and anti-inflammatory
      effects of propolis.

PMID- 28437892
TI  - High performance and low cost transparent electrodes based on ultrathin Cu layer.
AB  - Transparent electrodes based on an ultrathin Cu layer, embedded between two
      dielectrics, are optimized by simulations and experiments. Different dielectrics
      are screened in transfer matrix simulations for maximizing the broad-band
      transmittance. Based on this, sputtered electrodes were developed with the Cu
      embedded between TiO<sub>X</sub>-coated glass or PET substrate and an Al-doped
      ZnO (AZO) top layer. It is found that, for ultrathin Cu layers, increased sputter
      power fosters island coalescence, leading to superior optical and electrical
      performance compared to previously reported Cu-based electrodes. Simulations
      showed that the electrode design optimized with air as ambient medium has to be
      adapted in the case of electrode implementation in a hybrid perovskite solar cell
      of inverted architecture.

PMID- 28437891
TI  - The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol
      on experimental liver fibrosis.
AB  - OBJECTIVE: The present study aimed to compare the therapeutic efficiency of nano
      encapsulated and nano-emulsion carvacrol administration on liver injury in
      thioacetamide (TAA) treated rats. METHODS: To fulfill our target, we used sixty
      male albino rats classified into six groups as follow: control, nano-encapsulated
      carvacrol, nano-emulsion carvacrol, thioacetamide, treated nano-encapsulated
      carvacrol and treated nano-emulsion carvacrol groups. Blood samples were
      collected from all groups and the separated serum was used for analysis of the
      following biochemical parameters; aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), S100 B protein, alpha fetoprotein (AFP) and caspase-3.
      The levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide
      (NO), monocyte chemoattractant protein-1(MCP-1) and hydroxyproline content were
      all evaluated in liver tissue homogenate. Histopathological examinations for
      liver tissues were also performed. RESULTS: Thioacetamide induced hepatic damage
      in rats as revealed by the significant increase in the levels of serum ALT, AST
      and produced oxidative stress as displayed by the significant elevation in the
      levels of hepatic MDA and NO concomitant with a significant decrease in GSH. In
      addition, thioacetamide significantly increased serum S100B protein, alpha
      fetoprotein and caspase-3 along with hepatic MCP-1 and hydroxyproline; these
      results were confirmed by the histopathological investigation. In contrast, nano
      encapsulated and nano-emulsion carvacrol were able to ameliorate these negative
      changes in the thioacetamide injected rats. However, the effect of the nano
      encapsulated form of carvacrol was more prominent than the nano-emulsion form.
      CONCLUSION: Nano-encapsulated and nano-emulsion carvacrol can ameliorate
      thioacetamide induced liver injury. These results could be attributed to the
      potential anti-inflammatory, antioxidant, and anti-apoptotic activities of
      carvacrol in addition to the effectiveness of the encapsulation technique that
      can protect carvacrol structure and increase its efficiency and stability.
      Moreover, nano-encapsulation of carvacrol is more efficient than nano-emulsion.

PMID- 28437893
TI  - Ruthenium acetylacetonate in interface engineering for high performance planar
      hybrid perovskite solar cells.
AB  - As it already made huge effect in the commercialization of silicon and other
      photovoltaics, interface engineering is dispensable in the current and future
      evolution of hybrid perovskite solar cells (PSCs) techniques. In order to solve
      carriers' recombination and detention at the cathode side of planar PSCs, in this
      work, Ruthenium acetylacetonate (RuAcac) was successfully adopted as a reliable
      and stable cathode interfacial layer (CIL) to improve the inverted planar PSCs.
      The power conversion efficiency of the optimal devices was enhanced from 12.74%
      for the control device without RuAcac, to 17.15% for the RuAcac based devices,
      with an open circuit voltage of 1.077 V, a short circuit current density of 21.28
      mA/cm<sup>2</sup>, and fill factor of 74.7% correspondingly. A series of photon
      physics and microscopy protocols, including EQE, UPS, XPS, PL and SKPM, were used
      to discover the function of RuAcac CIL. Those results confirms an identical
      conclusion that RuAcac enables the formation of quasi-ohmic contact at the
      cathode side by eliminating the energy level barrier between the LUMO of PCBM and
      Fermi level of silver electrode. The low temperature and facile processed
      Ruthenium acetylacetonate in this work definitely offer us a robust interface
      engineering way for the perovskite solar cells and also their commercialization.

PMID- 28437894
TI  - Effect of anisotropic electron momentum distribution of surface plasmon on
      internal photoemission of a Schottky hot carrier device.
AB  - We recently reported that an Au/TiO<sub>2</sub> photonic crystal device for
      photochemical energy conversion showed a sub-bandgap photoresponse centered at
      the surface plasmon polariton (SPP) resonant wavelength of this device. Here we
      developed a theoretical modeling of the internal photoemission in this device by
      incorporating the effects of anisotropic hot electron momentum distribution
      caused by SPP. The influences of interband and intraband transition, anisotropic
      momentum distribution of hot electrons by SPP are integrated to model the
      internal quantum efficiency (IQE) of this device. Near resonant wavelength, SPP
      dominates the electric field in the thin Au layer, which generates hot electrons
      with high enough momentum preferentially normal to the Schottky interface.
      Compared with the widely used Fowler's theory of internal photoemission, our
      model better predicts hot electron collection in Schottky devices. This model
      will provide a design guidance for tuning and enhancing photoresponse of Schottky
      hot carrier devices.

PMID- 28437895
TI  - Aplanatic Fresnel optics.
AB  - We provide a general formulation for the design of any dual-surface aplanatic
      Fresnel optic (including combinations of refractive and reflective surfaces),
      with categories of devices that had not previously been recognized. Raytrace
      simulations for representative Fresnel aplanats in collimation (illumination)
      mode reveal compact designs with radiative efficiencies close to those of their
      aplanatic continuous non-Fresnel counterparts, and optical performance
      approaching the thermodynamic limit for radiative transfer.

PMID- 28437896
TI  - Variability of apparent and inherent optical properties of sediment-laden waters
      in large river basins - lessons from in situ measurements and bio-optical
      modeling.
AB  - We investigated the relationships between inherent and apparent optical
      properties (IOP and AOP, respectively) and suspended sediment concentrations
      (SSC) in the main Amazonian river waters. In situ measurements of SSC, remote
      sensing reflectance (R<sub>rs</sub>), the diffuse light attenuation coefficient
      (K<sub>d</sub>) and the total and non-algal particle (NAP) absorption
      coefficients (a<sub>TOT</sub> and a<sub>NAP</sub>, respectively) were conducted
      during three sampling trips along different streams of the Amazon River catchment
      (104 stations). The size distribution and chemical characteristics of the
      suspended sediment were also determined for 85 stations. We show that the
      particle size distribution (PSD) in the river water is best described by a
      segmented Junge power law distribution with a smaller slope value for the
      smallest particles (J<sub>1</sub> = 2.4) and a larger slope value (J<sub>2</sub>
      = 4.1) for the largest particles (> 10 um). A strong relationship was found
      between AOPs and IOPs and SSC when the entire data set was considered. However,
      for the Madeira River, the primary Amazon River tributary in terms of suspended
      sediment discharge, a significant dispersion was detected for the R<sub>rs</sub> 
      SSC relationship but not for the K<sub>d</sub> - SSC relationship. This
      dispersion has been shown by a previous study, using MODIS data, to display a
      seasonal pattern, which we investigated in this study using Mie modeling
      calibrated with suspended sediment characteristics. In the Madeira River,
      suspended sediment had a finer distribution size and a different mineralogy
      (e.g., a greater smectite content and a lower kaolinite content) during the
      rising water stage. Spectral variations of the imaginary part
      n<sup>'</sup>(lambda) of the refraction index also showed significant differences
      during the rising water stage. In contrast, other streams of the Amazon basin had
      very stable properties with respect to granulometry and mineralogy. Model
      simulations made possible to reproduce both field and satellite observations,
      showing that the R<sub>rs</sub> hysteresis observed in the Madeira River in the
      near infrared was mainly due to n<sup>'</sup>(lambda) seasonal variations,
      leading to a decrease of absorption during the rising water stage. K<sub>d</sub>
      was shown to remain stable because of its strong dependency on scattering
      processes. The model was used to further understand how suspended sediment size
      distribution and refraction index drive the IOPs in large rivers:
      n<sup>'</sup>(lambda) variations were shown to control primarily the reflectance
      variability; R<sub>rs</sub>(850) presented limited variations as a function of
      PSD in the range typical of large rivers (J<sub>1</sub> < 3) although it remained
      sensitive to particle mineralogical composition; R<sub>rs</sub>(670) showed the
      opposite behavior with a higher sensitivity to PSD variation for coarser PSD.
      Finally, we demonstrate that the use of the R<sub>rs</sub> ratio between the red
      and infrared channels allowed a reduction of the R<sub>rs</sub> sensitivity in
      all cases, by an average of 50% with respect to changes in the mineral
      composition or size distribution of suspended sediment. In particular, the
      R<sub>rs</sub> ratio varied by less than 5% for PSD representative of surface
      river waters.

PMID- 28437897
TI  - Investigation of transmission performance in multi-IFoF based mobile fronthaul
      with dispersion-induced intermixing noise mitigation.
AB  - We demonstrate the improvement of the transmission performance based on
      intermixing noise mitigation techniques in a multiple intermediate-frequency-over
      fiber (IFoF) based mobile fronthaul. The interaction between fiber chromatic
      dispersion and frequency chirp of the directly modulated laser generates the
      second-order distortion that degrades the performance of multi-IFoF transmission
      system. To avoid second-order distortion, we use intermediate frequency (IF)
      spacing optimization and octave-confined frequency plan schemes in which
      intermixing noise would be generated in the out of signal band and would not
      affect the quality of transmitted signal. For bandwidth efficient transmission of
      radio signal over mobile fronthaul link, we employ the dispersion compensation
      technique to suppress the intermixing noise sufficiently. For realization of the
      multi-IFoF based mobile fronthaul, we experimentally investigate the transmission
      performances of 48-, 72- and 144-IF carriers of the long term evolution-advanced
      (LTE-A) signals mapped with 64-quadrature amplitude modulation (QAM). It is
      clearly observed that the intermixing noise is suppressed owing to dispersion
      compensation technique and overall system performances are improved by IF spacing
      optimization and octave-confined frequency plan. As a result, we successfully
      transmit 144-IF carriers of the LTE-A signal with less than 8% error vector
      magnitude (EVM) over 20-km single-mode fiber (SMF) within only 3 GHz bandwidth.

PMID- 28437898
TI  - Near-infrared hybrid plasmonic multiple quantum well nanowire lasers.
AB  - The lasing characteristics of hybrid plasmonic AlGaAs/GaAs multiple quantum well
      (MQW) nanowire (NW) lasers beyond diffraction limit have been investigated by 3D
      finite-difference time-domain simulations. The results show that the hybrid
      plasmonic MQW NW has lower threshold gain over a broad diameter range in
      comparison with its photonic counterpart. Beyond the diffraction limit, the
      hybrid plasmonic MQW NW has a lowest threshold gain of 788 cm<sup>-1</sup> at a
      diameter of 130 nm, and a cutoff diameter of 80 nm, half that of the photonic
      lasers. In comparison with the hybrid plasmonic core-shell NWs, the hybrid
      plasmonic MQW NWs exhibit significantly lower threshold gain, higher Purcell
      factor, and smaller cutoff diameter, which are attributed to the superior overlap
      between the hybrid plasmonic modes and gain medium, as well as a stronger optical
      confinement due to the grating-like effect of MQW structures. Moreover, the
      hybrid plasmonic MQW NW has a lower threshold gain than that of the core-shell NW
      over a broad wavelength range. The hybrid plasmonic MQW NW structure is promising
      for ultrasmall and low-consumption near-infrared nanolasers.

PMID- 28437899
TI  - Adaptively loaded IM/DD optical OFDM based on set-partitioned QAM formats.
AB  - We investigate the constellation design and symbol error rate (SER) of set
      partitioned (SP) quadrature amplitude modulation (QAM) formats. Based on the SER
      analysis, we derive the adaptive bit and power loading algorithm for SP QAM based
      intensity-modulation direct-detection (IM/DD) orthogonal frequency division
      multiplexing (OFDM). We experimentally show that the proposed system
      significantly outperforms the conventional adaptively-loaded IM/DD OFDM and can
      increase the data rate from 36 Gbit/s to 42 Gbit/s in the presence of severe
      dispersion-induced spectral nulls after 40-km single-mode fiber. It is also shown
      that the adaptive algorithm greatly enhances the tolerance to fiber nonlinearity
      and allows for more power budget.

PMID- 28437900
TI  - Model and reconstruction of a K-edge contrast agent distribution with an X-ray
      photon-counting detector.
AB  - Contrast-enhanced computed tomography (CECT) helps enhance the visibility for
      tumor imaging. When a high-Z contrast agent interacts with X-rays across its K
      edge, X-ray photoelectric absorption would experience a sudden increment,
      resulting in a significant difference of the X-ray transmission intensity between
      the left and right energy windows of the K-edge. Using photon-counting detectors,
      the X-ray intensity data in the left and right windows of the K-edge can be
      measured simultaneously. The differential information of the two kinds of
      intensity data reflects the contrast-agent concentration distribution. K-edge
      differences between various matters allow opportunities for the identification of
      contrast agents in biomedical applications. In this paper, a general radon
      transform is established to link the contrast-agent concentration to X-ray
      intensity measurement data. An iterative algorithm is proposed to reconstruct a
      contrast-agent distribution and tissue attenuation background simultaneously.
      Comprehensive numerical simulations are performed to demonstrate the merits of
      the proposed method over the existing K-edge imaging methods. Our results show
      that the proposed method accurately quantifies a distribution of a contrast
      agent, optimizing the contrast-to-noise ratio at a high dose efficiency.

PMID- 28437901
TI  - One-dimensional stitching interferometry assisted by a triple-beam
      interferometer.
AB  - In this work, we proposed for stitching interferometry to use a triple-beam
      interferometer to measure both the distance and the tilt for all sub-apertures
      before the stitching process. The relative piston between two neighboring sub
      apertures is then calculated by using the data in the overlapping area.
      Comparisons are made between our method, and the classical least-squares
      principle stitching method. Our method can improve the accuracy and repeatability
      of the classical stitching method when a large number of sub-aperture
      topographies are taken into account. Our simulations and experiments on flat and
      spherical mirrors indicate that our proposed method can decrease the influence of
      the interferometer error from the stitched result. The comparison of stitching
      system with Fizeau interferometry data is about 2 nm root mean squares and the
      repeatability is within +/- 2.5 nm peak to valley.

PMID- 28437902
TI  - High-performance temperature sensing using a selectively filled solid-core
      photonic crystal fiber with a central air-bore.
AB  - A high-performance temperature sensor based on mode-coupling principle is
      proposed using a selectively filled, solid-core photonic crystal fiber with a
      central air-bore. The fibers are fabricated using the "stack-and-draw" method,
      with a micro scale central bore deliberately kept during the drawing procedure.
      The addition of the central air-bore enhances the mode-coupling efficiency
      between the fundamental core mode and modes in the high-index liquid-filled holes
      in the fiber cladding, therefore, the fiber can be used for a novel sensing
      architecture, when cladding holes are selectively filled with temperature
      sensitive liquids. Based on this concept, numerical analyses are accomplished
      using finite element method, showing that this fiber-based temperature sensor
      possesses high sensitivity of -6.02 nm/ degrees C, with a resolution of 3.32 *
      10<sup>-3</sup>  degrees C, in the temperature range from -80 to 90  degrees C.
      The selective hole-filling is verified by a multi-step infiltration technique. A
      particularly designed probe with improved sensitivity and manipulation is also
      proposed for this system.

PMID- 28437903
TI  - Real-time broadband radio frequency spectrum analyzer based on parametric spectro
      temporal analyzer (PASTA).
AB  - A real-time broadband radio frequency (RF) spectrum analyzer is proposed and
      experimentally demonstrated to rapidly measure the RF spectrum of broadband
      optical signal. Cross phase modulation in the highly-nonlinear fiber is used to
      convert the RF spectrum carried by the pump to the optical spectrum of the probe
      signal, then the optical spectrum is real-time analyzed with the parametric
      spectro-temporal analyzer (PASTA) technology. The system performances are
      investigated in detail, including bandwidth, resolution, frame rate, and dynamic
      range. It achieves large RF bandwidth of over 800 GHz, as well as 91-MHz frame
      rate without sacrificing the resolution. It is noted that 91-MHz frame rate is
      several orders of magnitude improvement over those previous reported all-optical
      RF spectrum analyzers. As a proof-of-concept demonstration, this real-time
      broadband RF spectrum analyzer successfully characterizes the ultra-short pulse
      trains with repetition rate of 160GHz, which is far beyond capability of the
      conventional electrical spectrum analyzer. It presents a new way to implement
      rapid and broadband RF spectrum measurement, and would be of great interests for
      some ultrafast scenarios, where the real-time RF spectrum analysis can be
      applied.

PMID- 28437904
TI  - Ray mapping with surface information for freeform illumination design.
AB  - A novel approach to incorporate surface information into the ray mapping method
      is proposed. This method calculates irradiance at the physical optical surface
      and target plane instead of the usually flat or hemispherical dummy surface,
      resulting in a mapping relationship which reflects the true geometry of the
      system. The robustness of the method is demonstrated in an extreme example (60
      degrees  off axis) where the uniformity is as high as 82%.

PMID- 28437905
TI  - Amplitude modulation of femtosecond laser pulses in the megahertz range for
      frequency-multiplexed two-photon imaging.
AB  - We present a frequency-multiplexed multi-site two-photon imaging method utilizing
      amplitude modulation of femtosecond laser pulses in the MHz range to tag each
      excitation beam and the corresponding fluorescence signals with specific
      frequencies. The frequency tags are generated with an interferometric scheme
      employing acousto-optic deflectors (AODs) to achieve precise spatial overlap of
      femtosecond laser pulses with periodically varying phase shift. Creating matching
      excitation beam patterns in each interferometer arm using multiple AOD driving
      frequencies, and subsequently overlapping these matching patterns, results in
      multiple encoded excitation beams with unique beat frequencies available for
      scanning. As a proof-of-concept, we demonstrate multiplexed two-photon image
      acquisition using test samples, and compare the performance of this approach to
      conventional two-photon laser scanning microscopy.

PMID- 28437906
TI  - Temperature-insensitive fiber optic Fabry-Perot interferometer based on special
      air cavity for transverse load and strain measurements.
AB  - We experimentally demonstrate transverse load and strain sensing based on a fiber
      optic Fabry-Perot interferometer (FPI) with special air cavity, which was created
      by fusion splicing single mode fiber (SMF), hollow core fiber (HCF) and several
      electrical arc discharges. The cavity height of this structure is higher than the
      cladding diameter of SMF so that it can sense transverse load with high
      sensitivity. The transverse load sensitivity of this air cavity FPI sensor is
      1.31 nm/N and about 5 times more sensitive compared to the current fiber tip
      interferometer (0.2526 nm/N). Meanwhile, this sensor also can measure strain and
      the strain sensitivity of 3.29 pm/MUepsilon is achieved. In addition, the low
      temperature sensitivity (1.08 pm/ degrees C) of the sensor can reduce the
      temperature-induced measurement error. This novel air cavity FPI can be developed
      and used as high-sensitivity transverse load and strain sensor with temperature
      insensitive.

PMID- 28437907
TI  - Back-focal-plane displacement detection using side-scattered light in dual-beam
      fiber-optic traps.
AB  - In optical traps the position of a trapped bead is usually determined by
      measuring the intensity distribution of the forward-scattered light and the back
      scattered light. In this paper we demonstrate that this position can be
      determined using the side-scattered light. A quadrant photodiode is used to
      monitor the position of an optically trapped object in a dual-beam fiber-optic
      trap by measurement of intensity shifts in the back focal plane of the objective
      that is perpendicular to the propagating beam. An approximated model based on ray
      optics is presented with numerical results that describe the use of the side
      scattered light for position detection. The influences of system parameters,
      including fiber separations, the numerical apertures (NA), and the radii of
      microspheres, are discussed in details. We find out that the displacement
      sensitivity of the detector is null for some critical radii and numerical
      apertures. In addition, the noises in laser powers are analyzed, and one power
      difference regime is proposed to weaken the influences.

PMID- 28437908
TI  - Ionization degree measurement in the gain medium of a hydrocarbon-free rubidium
      vapor laser operating in pulsed and CW modes.
AB  - Although the diode pumped alkali laser (DPAL) works in a three-level scheme,
      higher energy-state excitation and ionization processes exist during operation,
      which may lead to deleterious effects on laser performance. In this paper, we
      report the ionization degree measurement in the gain medium of an operational
      hydrocarbon-free Rb DPAL by using the optogalvanic method. The results show that,
      at the pulsed mode with a duration of ~1 ms, a maximal ionization degree of
      ~0.06% is obtained at a pump power of 140 W. While in the CW mode, the plasma
      reaches an ionization degree as high as ~2% at a pump power of 110 W, which is
      mainly due to the enough time for sufficient plasma development. A comparison
      with our previous work [Opt. Lett.39, 6501 (2014)] as well as modeling results is
      made and discussed. The influences of different population transfer channels on
      laser performance are simulated and analyzed. The results show that, for a
      typical hydrocarbon-free Rb laser (pump intensity of 15 kW/cm<sup>2</sup>, helium
      pressure of 10 atm and cell temperature of 438 K), all the high-energy excitation
      effects give an overall negative influence on laser efficiency of ~3.78%, while
      the top two influencing channels are the photoionization (~1.8%) and the energy
      pooling (~1.53%). The work in this paper experimentally reveals the influence of
      the macroscopic ionization evolution process on an operational DPAL for the first
      time, which would be helpful for a more comprehensive understanding of the
      physics in DPALs.

PMID- 28437909
TI  - Editorial: Optics Express - Now How Did That Happen?
AB  - Founding Editor-in-Chief Joseph Eberly tells how Optics Express was conceived as
      an entirely new kind of journal and the significant effort required to launch the
      first issue.

PMID- 28437910
TI  - Excitation enhancement in electric multipole transitions near a nanoedge.
AB  - We investigate enhancement of electric multipole excitations of atoms in the
      vicinity of an object with a nanoscale edge resulted from a large electromagnetic
      field gradient. We calculate the excitation efficiencies of a Rb atom around a
      nanoedge and find the excitations are enhanced by several orders of magnitude.
      The efficiencies with the change in the magnetic quantum number resolved are also
      examined. Each resolved efficiency shows rotationally symmetric spatial
      distribution, with continuous modification in shape from the far field to the
      near field. Furthermore, we estimate photon emission rates accompanied with
      multipole excitations in alkali (Rb and Cs) atoms and discuss the possibility to
      observe the enhancement in the multi-pole excitation in cold atoms.

PMID- 28437911
TI  - Investigation of third-order dispersion of long-range surface-plasmon-polariton
      waveguides using a Hong-Ou-Mandel interferometer.
AB  - High-order dispersion of long-range surface-plasmon-polariton waveguides (LR-SPP
      WGs) have been investigated using a two-photon interferometer. Since linear and
      even-ordered dispersions in two-photon interferometry are cancelled out by a
      nonlocal quantum correlation, odd-ordered dispersions of millimeter-long LR-SPP
      WGs are revealed. Even under the highly dispersive condition, the
      indistinguishability between two photons emerged from LR-SPP-WGs was well
      preserved. In addition, we demonstrated a strong polarization-selection by the LR
      SPP-WGs that leads to the polarization-stable and high-fidelity quantum
      interference.

PMID- 28437912
TI  - Switchable reflection/transmission utilizing polarization on a plasmonic
      structure consisting of self-assembly polystyrene spheres with silver patches.
AB  - We report a plasmonic structure for switchable reflection and transmission by
      polarization. The structure is composed of a hexagonal-packed polystyrene sphere
      array with silver patches on them. Simulations and experiments demonstrated that
      the conversions between reflected beams and transmitted ones can be performed
      when the polarization directions of incident beams vary from 0 degrees  to 90
      degrees . A switchable reflection and transmission at a given wavelength can be
      obtained, as long as sizes of PS spheres and azimuthal angles are properly
      chosen. Such a patchy plasmonic structure serving as a switch between reflection
      and transmission have potential applications in photoelectric control devices.

PMID- 28437913
TI  - Feature issue introduction: Light, Energy and the Environment, 2016.
AB  - This feature issue highlights contributions from authors who presented their
      research at the OSA Light, Energy and the Environment Congress, held in Leipzig,
      Germany from November 14 to 17, 2016.

PMID- 28437914
TI  - A Sagnac Fourier spectrometer.
AB  - A spectrometer based on a Sagnac interferometer, where one of the mirrors is
      replaced by a transmission grating, is introduced. Since the action of a
      transmission grating is reversible, both directions experience the same
      diffraction at a given wavelength. At the output, the crossed wavefronts are
      imaged onto a camera, where their Fizeau fringe pattern is recorded. Each
      spectral element produces a unique spatial frequency, hence the Fourier transform
      of the recorded interferogram contains the spectrum. Since the grating is tuned
      to place zero spatial frequency at a selected wavelength, the adjoining spectrum
      is heterodyned with respect to this wavelength. This spectrum can then be
      discriminated at a high spectral resolution from relatively low spatial
      frequencies. The spectrometer can be designed without moving parts for a
      relatively narrow spectral range or with a rotatable grating. The latter version
      bears the potential to be calibrated without a calibrated light source.

PMID- 28437915
TI  - Rapid thermal annealing treated spin-on doped antireflective radial junction Si
      nanopillar solar cell.
AB  - Radial junction nanopillar Si solar cells are interesting for cost effective
      efficiency improvement. Here, we address a convenient top-down fabrication of Si
      nanopillar solar cells using spin-on doping and rapid thermal annealing (RTA) for
      conformal PN junction formation. Broadband suppressed reflection as low as an
      average of 5% in the 300-1100 nm wavelength range and un-optimized cell
      efficiency of 7.3% are achieved. The solar cell performance can be improved by
      optimization of spin-on-doping and suitable surface passivation. Overall, the all
      RTA processed, spin-on doped nanopillar radial junction solar cell shows a very
      promising route for low cost and high efficiency thin film solar cell
      perspectives.

PMID- 28437916
TI  - Multiband selective absorbers made of 1D periodic Ag/SiO<sub>2</sub>/Ag
      core/shell coaxial cylinders horizontally lying on a planar substrate.
AB  - In this paper, we present a one-dimensional periodic microstructure for multiband
      selective absorbers of thermal radiation. The microstructure is made of
      Ag/SiO<sub>2</sub>/Ag core/shell coaxial cylinders horizontally lying on top of a
      SiO<sub>2</sub> dielectric spacer and an opaque silver substrate. The spectral
      directional absorptivity of the proposed structure was numerically investigated
      with the finite element based Comsol Multiphysics software. Multiband selective
      absorption in the wavenumber range from 2500 to 20000 cm<sup>-1</sup> for TM-wave
      incidence was obtained. Physical mechanisms responsible for the multiband
      selective absorption were elucidated due to the resonance of magnetic polaritons
      in the SiO<sub>2</sub> spacer shell, excitation of surface plasmon polaritons at
      the SiO<sub>2</sub>/Ag interface, and the effect of Wood's anomaly. Furthermore,
      the effects of a silver core radius, spacer shell thickness, a confocal
      elliptical core/shell cylinder on the property of multiband absorption, and the
      absorptivity of the structure with one core/four shells coaxial cylinders were
      explored.

PMID- 28437917
TI  - Vector radiative transfer model for coupled atmosphere and ocean systems
      including inelastic sources in ocean waters.
AB  - Inelastic scattering plays an important role in ocean optics. The main inelastic
      scattering mechanisms include Raman scattering, fluorescence by colored dissolved
      organic matter (FDOM), and fluorescence by chlorophyll. This paper reports an
      implementation of all three inelastic scattering mechanisms in the exact vector
      radiative transfer model for coupled atmosphere and ocean Systems (CAOS).
      Simulation shows that FDOM contributes to the water radiation field in the broad
      visible spectral region, while chlorophyll fluorescence is limited in a narrow
      band centered at 685 nm. This is consistent with previous findings in the
      literature. The fluorescence distribution as a function of depth and viewing
      angle is presented. The impacts of fluorescence to the degree of linear
      polarization (DoLP) and orientation of the polarization ellipse (OPE) are
      studied. The DoLP is strongly influenced by inelastic scattering at wavelengths
      with strong inelastic scattering contribution. The OPE is less affected by
      inelastic scattering but it has a noticeable impact, in terms of the angular
      region of positive polarization, in the backward direction. This effect is more
      apparent for deeper water depth.

PMID- 28437918
TI  - Modeling and designing multilayer 2D perovskite / silicon bifacial tandem
      photovoltaics for high efficiencies and long-term stability.
AB  - A key challenge in photovoltaics today is to develop cell technologies with both
      higher efficiencies and lower fabrication costs than incumbent crystalline
      silicon (c-Si) single-junction cells. While tandem cells have higher efficiencies
      than c-Si alone, it is generally challenging to find a low-cost, high-performance
      material to pair with c-Si. However, the recent emergence of 22% efficient
      perovskite photovoltaics has created a tremendous opportunity for high
      performance, low-cost perovskite / crystalline silicon tandem photovoltaic cells.
      Nonetheless, two key challenges remain. First, integrating perovskites into
      tandem structures has not yet been demonstrated to yield performance exceeding
      commercially available crystalline silicon modules. Second, the stability of
      perovskites is inconsistent with the needs of most end-users, who install
      photovoltaic modules to produce power for 25 years or more. Making these cells
      viable thus requires innovation in materials processing, device design,
      fabrication, and yield. We will address these two gaps in the photovoltaic
      literature by investigating new types of 2D perovskite materials with n
      butylammonium spacer layers, and integrating these materials into bifacial tandem
      solar cells providing at least 30% normalized power production. We find that an
      optimized 2D perovskite
      ((BA)<sub>2</sub>(MA)<sub>3</sub>(Sn<sub>0.6</sub>Pb<sub>0.4</sub>)<sub>4</sub>I<
      ub>13</sub>)/silicon bifacial tandem cell, given a globally average albedo of
      30%, yields a normalized power production of 30.31%, which should be stable for
      extended time periods without further change in materials or encapsulation.

PMID- 28437919
TI  - Polarization-based enhancement of ocean color signal for estimating suspended
      particulate matter: radiative transfer simulations and laboratory measurements.
AB  - Absorption and scattering by molecules, aerosols and hydrosols, and the
      reflection and transmission over the sea surface can modify the original
      polarization state of sunlight. However, water-leaving radiance polarization,
      containing embedded water constituent information, has largely been neglected.
      Here, the efficiency of the parallel polarization radiance (PPR) for enhancing
      ocean color signal of suspended particulate matter is examined via vector
      radiative transfer simulations and laboratory experiments. The simulation results
      demonstrate that the PPR has a slightly higher ocean color signal at the top-of
      atmosphere as compared with that of the total radiance. Moreover, both the
      simulations and laboratory measurements reveal that, compared with total
      radiance, PPR can effectively enhance the normalized ocean color signal for a
      large range of observation geometries, wavelengths, and suspended particle
      concentrations. Thus, PPR has great potential for improving the ocean color
      signal detection from satellite.

PMID- 28437920
TI  - CMOS-integrated GaN LED array for discrete power level stepping in visible light
      communications.
AB  - We report a CMOS integrated micro-LED array capable of generating discrete
      optical output power levels. A 16 * 16 array of individually addressable pixels
      are on-off controlled through parallel logic signals. With carefully selected
      groups of LEDs driven together, signals suitable for discrete transmission
      schemes are produced. The linearity of the device is assessed, and data
      transmission using pulse amplitude modulation (PAM) and orthogonal frequency
      division multiplexing (OFDM) is performed. Error-free transmission at a symbol
      rate of 100 MSamples/s is demonstrated with 4-PAM, yielding a data rate of 200
      Mb/s. For 8-PAM, encoding is required to overcome the baseline wander from the
      receiver, reducing the data rate to 150 Mb/s. We also present an experimental
      proof-of-concept demonstration of discrete-level OFDM, achieving a spectral
      efficiency of 3.96 bits/s/Hz.

PMID- 28437921
TI  - Development and evaluation of colour control interfaces for LED lighting.
AB  - To capitalise on the colour tuning capabilities of LED lighting, a model for
      converting device-specific control signals to chromaticity coordinates was used
      in a psychophysical experiment evaluating the usability of three colour control
      interfaces based on RGB (red, green, blue), HSB (hue, saturation, brightness) and
      opponent colour mixing systems. Although common and well accepted, the RGB
      interface had lowest usability based on both psychophysical results and
      subjective ratings. The usability of HSB and opponent colour interfaces was not
      significantly different. These findings can guide the development of useful and
      efficient colour control interfaces for tunable LED lighting systems.

PMID- 28437922
TI  - From toes to top-of-atmosphere: Fowler's Sneaker Depth index of water clarity for
      the Chesapeake Bay.
AB  - Fowler's Sneaker Depth (FSD), analogous to the well known Secchi disk depth
      (Zsd), is a visually discerned citizen scientist metric used to assess water
      clarity in the Patuxent River estuary. In this study, a simple remote sensing
      algorithm was developed to derive FSD from space-borne spectroradiometric
      imagery. An empirical model was formed that estimates FSD from red-end remote
      sensing reflectances at 645 nm, Rrs(645). The model is based on a hyperbolic
      function relating water clarity to Rrs(645) that was established using radiative
      transfer modeling and fine tuned using in-water FSD measurements and coincident
      Rrs(645) data observed by NASA's Moderate Resolution Imaging Spectroradiometer
      aboard the Aqua spacecraft (MODISA). The resultant FSD algorithm was applied to
      Landsat-8 Operational Land Imager data to derive a short time-series for the
      Patuxent River estuary from January 2015 to June 2016. Satellite-derived FSD had
      an inverse, statistically significant relationship (p<0.005) with total suspended
      sediment concentration (TSS). Further, a distinct negative relationship between
      FSD and chlorophyll concentration was discerned during periods of high biomass (>
      4 MUg L<sup>-1</sup>). The complex nature of water quality in the mid-to-upper
      Chesapeake Bay was captured using a MODISA-based FSD time series (2002-2016).
      This study demonstrates how a citizen scientist-conceived observation can be
      coupled with remote sensing. With further refinement and validation, the FSD may
      be a useful tool for delivering scientifically relevant results and for informing
      and engaging local stakeholders and policy makers.

PMID- 28437923
TI  - Nanoparticle-crystal towards an absorbing meta-coating.
AB  - In this paper, a double layer nanoparticle-crystal has been proposed, which shown
      incident and polarization angle, substrate independences for spectral
      absorptivity. Such phenomenon originates from the near-field light redistribution
      and excitation of internal collective oscillating. This kind of nanoparticle
      crystal can be made of various types of metal with similar optical responses. A
      three oscillators mode has been proposed in this paper to understand the shift
      between global and internal collective oscillating, and verify the physical
      picture demonstrated. That kind of near-field redistribution result in a
      prototype of novel meta-coating, and facilitates the large scale application of
      metamaterial.

PMID- 28437924
TI  - Synthesis and luminescence properties of
      Ba<sub>3</sub>Lu(PO<sub>4</sub>)<sub>3</sub>:Sm<sup>3+</sup> phosphor for white
      light-emitting diodes.
AB  - A series of Ba<sub>3</sub>Lu(PO<sub>4</sub>)<sub>3</sub>:Sm<sup>3+</sup>
      phosphors were prepared by traditional high temperature solid-state reaction
      methods. The site-preferred occupancy of Sm<sup>3+</sup> in
      Ba<sub>3</sub>Lu(PO<sub>4</sub>)<sub>3</sub> and the luminescence properties of
      Ba<sub>3</sub>Lu(PO<sub>4</sub>)<sub>3</sub>:Sm<sup>3+</sup> were studied
      combined with X-ray diffraction, photoluminescence excitation (PLE) spectra, and
      emission (PL) spectra as well as temperature-dependent PL and decay curves. The
      PL intensity is improved with increasing Sm<sup>3+</sup> content and the optimal
      dopant content is 0.05. The temperature-dependent PL spectra indicate that the
      emission intensity decreases with the temperature because of the enhancement of
      the non-radiative transition. The results indicate that these reddish-orange
      emitting phosphors could be for potential applications in w-LEDs.

PMID- 28437925
TI  - Back-contacted BaSi<sub>2</sub> solar cells: an optical study.
AB  - We present the optical investigation of a novel back-contacted architecture for
      solar cells based on a thin barium (di)silicide (BaSi<sub>2</sub>) absorber.
      First, through the analysis of absorption limits of different semiconducting
      materials, we show the potential of BaSi<sub>2</sub> for photovoltaic
      applications. Then, the proposed back contacted BaSi<sub>2</sub> solar cell
      design is investigated and optimized. An implied photocurrent density of 40.3
      mA/cm<sup>2</sup> in a 1-MUm thick absorber was achieved, paving the way for
      novel BaSi<sub>2</sub>-based thin-film solar cells.

PMID- 28437926
TI  - Demonstration of a dual-mode Si detector as a self-calibrating device at room
      temperature.
AB  - We demonstrate the use of a dual-mode detector for determining the internal
      quantum deficiency of a silicon photodiode without the use of an external
      reference. This is achieved by combining two different principles for measuring
      optical power in one device, where the photodiode is used as absorber for both
      thermal and photon detection. Thermal detection is obtained by the same principle
      as for an electrical substitution radiometer (ESR), with a type A measurement
      uncertainty of 0.34 % in unstabilized room temperature. The optical power
      measured in thermal mode was around 3 % +/- 0.5 % higher than what was measured
      in photocurrent mode. Heat transfer simulations revealed a difference of up to
      2.2 % between optical and electrical heating, and based on these simulations we
      give recommendations for improvements of the detector thermal design.

PMID- 28437927
TI  - Precision measurement of magnetic field based on the transient process in a K-Rb
      <sup>21</sup>Ne co-magnetometer.
AB  - We demonstrate a novel method of measuring magnetic field based on the transient
      signal of the K-Rb-<sup>21</sup>Ne co-magnetometer operating in nuclear spin
      magnetization self-compensation magnetic field regime. The operation condition
      for self-compensation magnetic field by nuclear spin magnetization of
      <sup>21</sup>Ne in steady state is presented. We characterize the dynamics of the
      coupled spin ensembles by a set of Bloch equations, and formulate the expression
      of transient output signal. After verifying the stability of this method, the
      measurement range and error are studied. This method is also verified to be valid
      in various temperature and pumping light power density.

PMID- 28437928
TI  - Terahertz optical bistability of graphene in thin layers of dielectrics.
AB  - We theoretically studied in terahertz frequency regime optical bistability of
      graphene placed at the interface between thin dielectric layers. We solved self
      consistently the nonlinear wave equations containing the third-order optical
      conductivity of graphene in four-layer structures and obtained hysteresis
      response of the transmitted power as a function of the incident power. We
      numerically observed that the critical powers for the up and down transitions and
      the Fermi-energy of graphene required for terahertz optical bistability can be
      reduced by carefully choosing material properties and the thicknesses of
      dielectric layers. Furthermore, these values can be substantially decreased when
      graphene as a randomly stacked multilayer structure is asymmetrically located in
      thin dielectric layers.

PMID- 28437929
TI  - Robust overlay metrology with differential Mueller matrix calculus.
AB  - Overlay control is of vital importance to good device performances in
      semiconductor manufacturing. In this work, the differential Mueller matrix
      calculus is introduced to investigate the Mueller matrices of double-patterned
      gratings with overlay displacements, which helps to reveal six elementary optical
      properties hidden in the Mueller matrices. We find and demonstrate that, among
      these six elementary optical properties, the linear birefringence and dichroism,
      LB' and LD', along the +/- 45 degrees  axes show a linear response to the overlay
      displacement and are zero when the overlay displacement is absent at any conical
      mounting. Although the elements from the two 2 * 2 off-diagonal blocks of the
      Mueller matrix have a similar property to LB' and LD', as reported in the
      literature, we demonstrate that it is only valid at a special conical mounting
      with the plane of incidence parallel to grating lines. The better property of LB'
      and LD' than the Mueller matrix elements of the off-diagonal blocks in the
      presence of overlay displacement verifies them to be a more robust indicator for
      the diffraction-based overlay metrology.

PMID- 28437930
TI  - SI-traceable measurement of an optical frequency at the low 10<sup>-16</sup>
      level without a local primary standard.
AB  - SI-traceable measurements of optical frequencies using International Atomic Time
      (TAI) do not require a local primary frequency reference, but suffer from an
      uncertainty in tracing to the SI second. For the measurement of the
      <sup>87</sup>Sr lattice clock transition, we have reduced this uncertainty to the
      low 10<sup>-16</sup> level by averaging three sets of ten-day intermittent
      measurements, in which we operated the lattice clock for 10<sup>4</sup> s on each
      day. Moreover, a combined oscillator of two hydrogen masers was employed as a
      local flywheel oscillator (LFO) in order to mitigate the impact of sporadic
      excursion of LFO frequency. The resultant absolute frequency with fractional
      uncertainty of 4.3 * 10<sup>-16</sup> agrees with other measurements based on
      local state-of-the-art cesium fountains.

PMID- 28437931
TI  - Circular core single-mode polymer optical waveguide fabricated using the Mosquito
      method with low loss at 1310/1550 nm.
AB  - We fabricate low-loss single-mode (SM) polymer optical waveguides using a
      photomask-free simple technique named the Mosquito method. The insertion losses
      of a 5-cm long SM polymer waveguide fabricated are 2.52 dB and 4.03 dB at 1310-
      and 1550-nm wavelengths, respectively. The coupling loss between a single-mode
      fiber and the waveguide is as low as 0.5 dB including the Fresnel reflection. The
      0.5-dB misalignment tolerance in the radial direction is +/- 2.0 MUm at 1550 nm.
      The Mosquito method is promising for fabricating SM polymer optical waveguides
      compatible with silicon photonics chips.

PMID- 28437932
TI  - Electrifying catheters with light.
AB  - Smart minimally invasive devices face a connectivity challenge. An example is
      found in intracardiac echocardiography where the signal transmission and supply
      of power at the distal end require many thin and fragile wires in order to keep
      the catheter slim and flexible. We have built a fully functional bench-top
      prototype to demonstrate that electrical wires may be replaced by optical fibers.
      The prototype is immediately scalable to catheter dimensions. The absence of
      conductors will provide intrinsic galvanic isolation as well as radio frequency
      (RF) and magnetic resonance imaging (MRI) compatibility. Using optical fibers, we
      show signal transfer of synthetic aperture ultrasound images as well as photo
      voltaic conversion to supply all electronics. The simple design utilizes only off
      the shelf components and holds a promise of cost effectiveness which may be
      pivotal for translation of these advanced devices into the clinic.

PMID- 28437933
TI  - Optical wave parameters for spatially dispersive and anisotropic nanomaterials.
AB  - Spatial dispersion is an intriguing property of essentially all nanostructured
      optical media. In particular, it makes optical waves with equal frequencies and
      polarizations have different wavelengths, if they propagate in different
      directions. This can offer new approaches to control light radiation and
      propagation. Spatially dispersive nanomaterials, such as metamaterials, are often
      treated in terms of wave parameters, such as refractive index and impedance
      retrieved from reflection and transmission coefficients of the material at each
      incidence angle. Usually, however, the waves are approximated as transverse,
      which simplifies the description, but yields wrong results, if spatial dispersion
      or optical anisotropy is significant. In this work, we present a method to
      calculate the wave parameters of a general spatially dispersive and optically
      anisotropic medium without applying such an approximation. The method allows one
      to evaluate the true impedances and field vectors of the effective waves,
      obtaining thus the true light intensity and energy propagation direction in the
      medium. The equations are applied to several examples of spatially dispersive and
      anisotropic materials. The method introduces new insights into optics of
      nanostructured media and extends the design of such media towards optical
      phenomena involving significant spatial dispersion.

PMID- 28437934
TI  - Dual channel multilayer-coated surface plasmon resonance sensor for dual
      refractive index range measurements.
AB  - We present a novel multilayer-coated surface plasmon resonance sensor for dual
      refractive index range measurements based on a capillary structure. The sensing
      elements include an internally coated Ag layer and an externally coated bilayer
      of Au with an overlayer of thin indium tin oxide (ITO). The internal Ag layer was
      sensitive to higher refractive index (RI) medium while the external Au/ITO layer
      was sensitive to lower refractive index medium. We evaluated the sensor
      performance by measuring RI changes in two channels, RI sensitivities were -1951
      nm/RIU and 2496 nm/RIU, respectively. This compact, low-cost large RI detection
      range SPR sensor offers the possibility for wider RI detection range and highly
      sensitive SPR studies in industry and chemical sensing.

PMID- 28437935
TI  - Terahertz artificial material based on integrated metal-rod-array for phase
      sensitive fluid detection.
AB  - A terahertz artificial material composed of metal rod array is experimentally
      investigated on its transmission spectral property and successfully incorporated
      into microfluidics as a miniaturized terahertz waveguide with an extended optical
      path-length for label-free fluidic sensing. Theoretical and experimental
      characterizations of terahertz transmission spectra show that the wave guidance
      along the metal rod array originates from the resonance of transverse-electric
      polarized waves within the metal rod slits. The extended optical path length
      along three layers of metal-rod-array enables terahertz waves sufficiently
      overlapping the fluid molecules embedded among the rods, leading to strongly
      enhanced phase change by approximately one order of magnitude compared with the
      blank metal-parallel-plate waveguide. Based on the enhanced phase sensitivity,
      three kinds of colorless liquid analytes, namely, acetone, methanol, and ethanol,
      with different dipole moments are identified in situ using the metal-rod-array
      based microfluidic sensor. The detection limit in molecular amounts of a liquid
      analyte is experimentally demonstrated to be less than 0.1 mmol, corresponding to
      2.7 MUmol/mm<sup>2</sup>. The phase sensitive terahertz metal-rod-array-based
      sensor potentially has good adaptability in lab-chip technology for various
      practical applications, such as industrial toxic fluid detection and medical
      breath inspection.

PMID- 28437936
TI  - Ultra-thin and high-efficiency graphene metasurface for tunable terahertz wave
      manipulation.
AB  - We propose a type of ultra-thin metasurfaces composed of rectangular graphene
      patches supporting orthogonal plasmonic resonances, which can work in
      transmission or reflection modes for dynamic terahertz wavefront manipulation
      with high polarization conversion ratio. By controlling the response of each
      patch via electrical biasing, the phase of the output wave can be tuned in a wide
      range over 180 degrees  while keeping its amplitude high and relatively stable.
      We demonstrate several functional devices based on such metasurfaces: a linear
      polarization converter with nearly 100% polarization conversion ratio, a
      switchable anomalous wave deflection device, and a dual-polarity focusing mirror
      with the focal spot tunable in both the transversal and longitudinal directions.

PMID- 28437937
TI  - Use of Kramers-Kronig relation in phase retrieval calculation in X-ray spectro
      ptychography.
AB  - Coherent diffraction imaging (CDI) is a method for reconstructing the complex
      valued image of an object from diffraction intensities by using iterative phasing
      methods. X-ray ptychography is a scanning type of CDI using X-rays, allowing us
      to visualize the complex transmission function of an extended specimen. We here
      propose the use of the Kramers-Kronig relation (KKR) as an additional constraint
      in phase retrieval algorithms for multiple-energy X-ray ptychography using the
      absorption edge of a specific element. A numerical simulation showed that the
      speed of convergence was increased by using the improved algorithm with the KKR.
      We successfully demonstrated its usefulness in a proof-of-principle experiment at
      SPring-8. The present algorithm is particularly useful for imaging X-ray
      absorption fine structures of a specific element buried within thick samples by
      hard X-ray spectro-ptychography.

PMID- 28437938
TI  - Focus issue introduction: Advanced Solid-State Lasers (ASSL) 2016.
AB  - The editors introduce the focus issue on "Advanced Solid-State Lasers (ASSL)
      2016", which is based on the topics presented at a conference of the same name
      held in Boston, USA, from October 30 to November 3, 2016. This focus issue,
      jointly prepared by Optics Express and Optical Materials Express, includes 20
      contributed papers (14 for Optics Express and 6 for Optical Materials Express)
      selected from the voluntary submissions from attendees who presented at the
      conference and have extended their work into complete research articles. We hope
      this focus issue provides a useful link to the variety of topical discussions
      held at the conference and will contribute to the further expansion of the
      associated research areas.

PMID- 28437939
TI  - Exploiting high-order phase-shift keying modulation and direct-detection in
      silicon photonic systems.
AB  - A computational approach to evaluate the bit-error ratio (BER) in silicon
      photonic systems employing high-order phase-shift keying (PSK) modulation formats
      is presented. Specifically, the investigated systems contain a silicon based
      optical interconnect, namely a strip silicon photonic waveguide or a silicon
      photonic crystal waveguide, and direct-detection receivers suitable to detect PSK
      and amplitude-shaped PSK signals. The superposition of a PSK signal and complex
      additive white Gaussian noise passes through the optical interconnect and
      subsequently through two detection-branch receivers. To model the signal
      propagation in the silicon optical interconnects we used a modified nonlinear
      Schrodinger equation, which incorporates all relevant linear and nonlinear
      optical effects and the mutual interaction between free-carriers and the optical
      field. Finally, the BER is calculated by applying a frequency-domain approach
      based on the Karhunen-Loeve series expansion method. Our computational studies of
      the BER reveal that the optical power, type of PSK modulation, waveguide length,
      and group-velocity are key factors characterizing the system BER, their influence
      on BER being more significant in a photonic system with larger nonlinearity. In
      particular, our analysis shows that the system performance is affected to a much
      larger extent when the signal propagates in the slow-light regime, despite the
      fact that this regime allows for a significantly reduced length of optical
      interconnects.

PMID- 28437940
TI  - Rydberg-atom based radio-frequency electrometry using frequency modulation
      spectroscopy in room temperature vapor cells.
AB  - Rydberg atom-based electrometry enables traceable electric field measurements
      with high sensitivity over a large frequency range, from gigahertz to terahertz.
      Such measurements are particularly useful for the calibration of radio frequency
      and terahertz devices, as well as other applications like near field imaging of
      electric fields. We utilize frequency modulated spectroscopy with active control
      of residual amplitude modulation to improve the signal to noise ratio of the
      optical readout of Rydberg atom-based radio frequency electrometry. Matched
      filtering of the signal is also implemented. Although we have reached similarly,
      high sensitivity with other read-out methods, frequency modulated spectroscopy is
      advantageous because it is well-suited for building a compact, portable sensor.
      In the current experiment, ~3 uV cm<sup>-1</sup> Hz<sup>-1/2</sup> sensitivity is
      achieved and is found to be photon shot noise limited.

PMID- 28437941
TI  - Effect of scattering on coherent anti-Stokes Raman scattering (CARS) signals.
AB  - We develop a computational framework to examine the factors responsible for
      scattering-induced distortions of coherent anti-Stokes Raman scattering (CARS)
      signals in turbid samples. We apply the Huygens-Fresnel wave-based electric field
      superposition (HF-WEFS) method combined with the radiating dipole approximation
      to compute the effects of scattering-induced distortions of focal excitation
      fields on the far-field CARS signal. We analyze the effect of spherical
      scatterers, placed in the vicinity of the focal volume, on the CARS signal
      emitted by different objects (2MUm diameter solid sphere, 2MUm diameter myelin
      cylinder and 2MUm diameter myelin tube). We find that distortions in the CARS
      signals arise not only from attenuation of the focal field but also from
      scattering-induced changes in the spatial phase that modifies the angular
      distribution of the CARS emission. Our simulations further show that CARS signal
      attenuation can be minimized by using a high numerical aperture condenser.
      Moreover, unlike the CARS intensity image, CARS images formed by taking the ratio
      of CARS signals obtained using x- and y-polarized input fields is relatively
      insensitive to the effects of spherical scatterers. Our computational framework
      provide a mechanistic approach to characterizing scattering-induced distortions
      in coherent imaging of turbid media and may inspire bottom-up approaches for
      adaptive optical methods for image correction.

PMID- 28437942
TI  - Optical damage resistant Ti-diffused Zr/Er-codoped lithium niobate strip
      waveguide for high-power 980 nm pumping.
AB  - Ti<sup>4+</sup>-diffused Zr<sup>4+</sup>/Er<sup>3+</sup>-codoped
      LiNbO<sub>3</sub> strip waveguide was fabricated on an X-cut LiNbO<sub>3</sub>
      substrate by thermal diffusion in sequence of Er<sup>3+</sup>, Zr<sup>4+</sup>
      and Ti<sup>4+</sup>. Secondary ion mass spectrometry study shows that the
      Ti<sup>4+</sup> ions follow a sum of two error functions in the width direction
      and a Gauss function in the depth direction of the waveguide. Both
      Er<sup>3+</sup> and Zr<sup>4+</sup> profiles follow the desired Gauss function,
      and entirely cover the Ti<sup>4+</sup> profile. Optical study shows that the
      waveguide is TE or TM single mode at 1.5 MUm wavelength, and has a loss of 0.3
      (0.5) dB/cm for the TM (TE) mode. In the case of 980 nm pumping, the waveguide
      shows stable 1547 nm signal output under high-power pumping without optical
      damage observed, and a net gain of 1.1 dB/cm is obtained for the available pump
      power of 120 mW.

PMID- 28437943
TI  - Power allocation for uniform illumination with stochastic LED arrays.
AB  - In this paper, a simple heuristic power allocation scheme is proposed for a
      random LED array to obtain uniform irradiance on the projection surface. This is
      done by considering a binomial point process (BPP) for modeling the LED location
      and using the quality factor as a performance metric. Numerical results are
      provided to validate the proposed model and demonstrate its simplicity over
      existing LED geometries.

PMID- 28437944
TI  - Calibrating high intensity absorption imaging of ultracold atoms.
AB  - Absorption imaging of ultracold atoms is the foundation for quantitative
      extraction of information from experiments with ultracold atoms. Due to the
      limited exposure time available in these systems, the signal-to-noise ratio is
      largest for high intensity absorption imaging where the intensity of the imaging
      light is on the order of the saturation intensity. In this case, the absolute
      value of the intensity of the imaging light enters as an additional parameter
      making it more sensitive to systematic errors. Here, we present a novel and
      robust technique to determine the imaging beam intensity in units of the
      effective saturation intensity to better than 5%. We do this by measuring the
      momentum transferred to the atoms by the imaging light while varying its
      intensity. We further utilize the method to quantify the purity of the
      polarization of the imaging light and to determine the correct imaging detuning.

PMID- 28437945
TI  - Experimental demonstration of wideband multimodule serial reflectors.
AB  - We demonstrate unpolarized wideband reflectors fashioned with orthogonal serial
      resonant reflectors. Unpolarized incident light generates internal TM- and TE
      polarized reflections that are made to cooperate to extend the bandwidth of the
      composite spectral reflectance. The experimental results presented show ~42% band
      extension by a two-grating module. In addition, good angular tolerance is found
      because the orthogonal arrangement simultaneously supports classical and fully
      conic mountings at oblique angles. The resulting spectra form contiguous zero
      order reflectance across wide spectral/angular regions. Furthermore, using a
      multimodule device with serial reflectors fabricated with silicon-on-quartz
      wafers with different device layer thicknesses, extreme band extension is
      achieved providing ~56% fractional bandwidth with reflectance exceeding 98%.
      These results imply potential for developing lossless unpolarized mirrors
      operating in diverse spectral regions of practical interest.

PMID- 28437946
TI  - Cyphertext-only attack on the double random-phase encryption: Experimental
      demonstration.
AB  - We demonstrate experimentally that the traditional double random phase encoding
      (DPRE) technique is vulnerable to the cyphertext-only attack (COA). With the
      statistical ergodic property of the speckle, we show that the plaintext image can
      be recovered from the cyphertext alone owing to the fact that their energy
      spectral density functions are identical. Our result reveals the most serious
      security issue with the DRPE as it suggests that even the one-time-pad does not
      guarantee its security. This will open up new inside understanding of current
      optical security techniques.

PMID- 28437947
TI  - Hard x-ray scanning imaging achieved with bonded multilayer Laue lenses.
AB  - We report scanning hard x-ray imaging with a monolithic focusing optic consisting
      of two multilayer Laue lenses (MLLs) bonded together. With optics pre
      characterization and accurate control of the bonding process, we show that a
      common focal plane for both MLLs can be realized at 9.317 keV. Using bonded MLLs,
      we obtained a scanning transmission image of a star test pattern with a
      resolution of 50 * 50 nm<sup>2</sup>. By applying a ptychography algorithm, we
      obtained a probe size of 17 * 38 nm<sup>2</sup> and an object image with a
      resolution of 13 * 13 nm<sup>2</sup>. The significant reduction in alignment
      complexity for bonded MLLs will greatly extend the application range in both
      scanning and full-field x-ray microscopies.

PMID- 28437948
TI  - UV-sensitive superconducting nanowire single photon detectors for integration in
      an ion trap.
AB  - We demonstrate superconducting nanowire single photon detectors with 76 +/- 4%
      system detection efficiency at a wavelength of 315 nm and an operating
      temperature of 3.2 K, with a background count rate below 1 count per second at
      saturated detection efficiency. We propose integrating these detectors into
      planar surface electrode radio-frequency Paul traps for use in trapped ion
      quantum information processing. We operate detectors integrated into test ion
      trap structures at 3.8 K both with and without typical radio-frequency trapping
      electric fields. The trapping fields reduce system detection efficiency by 9%,
      but do not increase background count rates.

PMID- 28437949
TI  - Ultrafast all-optical solid-state framing camera with picosecond temporal
      resolution.
AB  - A new ultrafast all-optical solid-state framing camera (UASFC) capable of single
      shot ultrafast imaging is proposed and experimentally demonstrated. It is
      composed of an ultrafast semiconductor chip (USC), an optical time-series system
      (TSS), and a spatial mapping device (SMD) with an USC to transform signal beam
      information to the probe beam, a TSS to convert the time axis to wavelength
      polarization, and a SMD to map wavelength-polarization image to different spatial
      positions. In our recent proof-of-principle experiment, better performance than
      ever of this technique is confirmed by giving six frames with ~3 ps temporal
      resolution and ~30 lp/mm spatial resolution.

PMID- 28437950
TI  - Maximum likelihood sequence estimation for optical complex direct modulation.
AB  - Semiconductor lasers are versatile optical transmitters in nature. Through the
      direct modulation (DM), the intensity modulation is realized by the linear
      mapping between the injection current and the light power, while various angle
      modulations are enabled by the frequency chirp. Limited by the direct detection,
      DM lasers used to be exploited only as 1-D (intensity or angle) transmitters by
      suppressing or simply ignoring the other modulation. Nevertheless, through the
      digital coherent detection, simultaneous intensity and angle modulations (namely,
      2-D complex DM, CDM) can be realized by a single laser diode. The crucial
      technique of CDM is the joint demodulation of intensity and differential phase
      with the maximum likelihood sequence estimation (MLSE), supported by a closed
      form discrete signal approximation of frequency chirp to characterize the MLSE
      transition probability. This paper proposes a statistical method for the
      transition probability to significantly enhance the accuracy of the chirp model.
      Using the statistical estimation, we demonstrate the first single-channel 100
      Gb/s PAM-4 transmission over 1600-km fiber with only 10G-class DM lasers.

PMID- 28437951
TI  - Hot-spot relaxation time current dependence in niobium nitride waveguide
      integrated superconducting nanowire single-photon detectors.
AB  - We investigate how the bias current affects the hot-spot relaxation dynamics in
      niobium nitride. We use for this purpose a near-infrared pump-probe technique on
      a waveguide-integrated superconducting nanowire single-photon detector driven in
      the two-photon regime. We observe a strong increase in the picosecond relaxation
      time for higher bias currents. A minimum relaxation time of (22 +/- 1) ps is
      obtained when applying a bias current of 50% of the switching current at 1.7 K
      bath temperature. We also propose a practical approach to accurately estimate the
      photon detection regimes based on the reconstruction of the measured detector
      tomography at different bias currents and for different illumination conditions.

PMID- 28437952
TI  - Real-time observation of round-trip resolved spectral dynamics in a stabilized fs
      fiber laser.
AB  - Fiber-stretcher based phase-lock loop (PLL) is a mature technique in fiber mode
      locked lasers for repetition-rate stabilization. However, undesired side effects
      may be induced if not properly handled, which is easily overlooked owing to the
      lack of single-shot spectral analyzers. Thanks to the ultrafast spectral
      analyzing capability of optical time-stretch, an intriguing spectral dynamics is
      observed in a repetition-rate-stabilized nonlinear polarization rotation (NPR)
      mode-locked laser. Under the dynamic state, the optical spectra of pulses undergo
      dramatic evolution in every round trip while the pulse energy is relatively
      constant. Indicated by estimated cross-spectral densities, such spectral dynamics
      results in noticeable degradation in optical spectral coherence. The physical
      origin of the round-trip evolved spectral dynamics is attributed to the local
      birefringence induced by the fiber stretcher. Therefore, the results are helpful
      for a proper use of fiber-stretcher based PLL in fiber lasers, particularly when
      a good spectral coherence is desired. Furthermore, our study has also provided a
      potentially useful optical source for applications where fast spectral modulation
      is desired.

PMID- 28437953
TI  - High power cladding light stripper using segmented corrosion method: theoretical
      and experimental studies.
AB  - We present the segmented corrosion method that uses hydrofluoric acid to etch the
      fiber of a fiber laser for removing high-power cladding light to improve
      stripping uniformity and power handling capability. For theoretical guidelines,
      we propose a simulation model of etched-fiber stripping to evaluate the
      relationship between the etched-fiber parameters and cladding light attenuation
      and to analyze the stripping uniformity achieved with segmented corrosion. A two
      segment etched fiber is fabricated with cladding light attenuation of 19.8 dB and
      power handling capability up to 670 W. We find that the cladding light is
      stripped uniformly and the temperature distribution is uniform without the
      formation of hot spots.

PMID- 28437954
TI  - Microstructured FBG hydrogen sensor based on Pt-loaded WO<sub>3</sub>.
AB  - Hydrogen gas sensing properties of Pt-WO<sub>3</sub> films on spiral
      microstructured fiber Bragg grating (FBG) has been demonstrated. Pt
      WO<sub>3</sub> film was prepared by hydrothermal method. The spiral
      microsturctured FBG was fabricated using femtosecond laser. Spiral microstructure
      FBG hydrogen sensor can detect hydrogen concentration from 0.02% H<sub>2</sub> to
      4% H<sub>2</sub> at room temperature, and the response time is shortened from a
      few minutes to 10~30 s. Double spiral microstructure at pitch 60 MUm and
      sputtered with 2 MUm Pt-WO<sub>3</sub> film recorded hydrogen sensitivity of 522
      pm/%(v/v) H<sub>2</sub> responding to hydrogen gas in air. This translated to
      approximately 2~4 times higher than the unprocessed standard FBG. The humidity
      has little effect on the sensing property. The sensor has fast response time,
      good stability, large detection range and has the good prospect of practical
      application for hydrogen leak detection.

PMID- 28437955
TI  - Cyclic coding for Brillouin optical time-domain analyzers using probe dithering.
AB  - We study the performance limits of mono-color cyclic coding applied to Brillouin
      optical time-domain analysis (BOTDA) sensors that use probe wave dithering. BOTDA
      analyzers with dithering of the probe use a dual-probe-sideband setup in which an
      optical frequency modulation of the probe waves along the fiber is introduced.
      This avoids non-local effects while keeping the Brillouin threshold at its
      highest level, thus preventing the spontaneous Brillouin scattering from
      generating noise in the deployed sensing fiber. In these conditions, it is
      possible to introduce an unprecedented high probe power into the sensing fiber,
      which leads to an enhancement of the signal-to-noise ratio (SNR) and consequently
      to a performance improvement of the analyzer. The addition of cyclic coding in
      these set-ups can further increase the SNR and accordingly enhance the
      performance. However, this unprecedented probe power levels that can be employed
      result in the appearance of detrimental effects in the measurement that had not
      previously been observed in other BOTDA set-ups. In this work, we analyze the
      distortion in the decoding process and the errors in the measurement that this
      distortion causes, due to three factors: the power difference of the successive
      pulses of a code sequence, the appearance of first-order non-local effects and
      the non-linear amplification of the probe wave that results when using mono-color
      cyclic coding of the pump pulses. We apply the results of this study to
      demonstrate the performance enhancement that can be achieved in a long-range
      dithered dual-probe BOTDA. A 164-km fiber-loop is measured with 1-m spatial
      resolution, obtaining 3-MHz Brillouin frequency shift measurement precision at
      the worst contrast location. To the best of our knowledge, this is the longest
      sensing distance achieved with a BOTDA sensor using mono-color cyclic coding.

PMID- 28437956
TI  - Single-shot areal profilometry using hyperspectral interferometry with a
      microlens array.
AB  - We describe a single-shot technique to measure areal profiles on optically smooth
      and stepped surfaces for applications where rapid data acquisition in non
      cooperative environments is essential. It is based on hyperspectral
      interferometry (HSI), a technique in which the output of a white-light
      interferometer provides the input to a hyperspectral imaging system. Previous HSI
      implementations suffered from inefficient utilisation of the available pixels
      which limited the number of measured coordinates and/or unambiguous depth range.
      In the current paper a >20-fold increase in pixel utilisation is achieved through
      the use of a 2-D microlens array, that leads to a 35 * 35 channel system with an
      unambiguous depth range of 0.88 mm.

PMID- 28437957
TI  - Widely wavelength tunable gain-switched Er<sup>3+</sup>-doped ZBLAN fiber laser
      around 2.8 MUm.
AB  - In this paper, we demonstrate a wavelength widely tunable gain-switched
      Er<sup>3+</sup>-doped ZBLAN fiber laser around 2.8 MUm. The laser can be tuned
      over 170 nm (2699 nm~2869.9 nm) for various pump power levels, while maintaining
      stable MUs-level single-pulse gain-switched operation with controllable output
      pulse duration at a selectable repetition rate. To the best of our knowledge,
      this is the first wavelength tunable gain-switched fiber laser in the 3 MUm
      spectral region with the broadest tuning range (doubling the record tuning range)
      of the pulsed fiber lasers around 3 MUm. Influences of pump energy and power on
      the output gain-switched laser performances are investigated in detail. This
      robust, simple, and versatile mid-infrared pulsed fiber laser source is highly
      suitable for many applications including laser surgery, material processing,
      sensing, spectroscopy, as well as serving as a practical seed source in master
      oscillator power amplifiers.

PMID- 28437958
TI  - Feed-forward frequency offset estimation for 32-QAM optical coherent detection.
AB  - Due to the non-rectangular distribution of the constellation points, traditional
      fast Fourier transform based frequency offset estimation (FFT-FOE) is no longer
      suitable for 32-QAM signal. Here, we report a modified FFT-FOE technique by
      selecting and digitally amplifying the inner QPSK ring of 32-QAM after the
      adaptive equalization, which is defined as QPSK-selection assisted FFT-FOE.
      Simulation results show that no FOE error occurs with a FFT size of only 512
      symbols, when the signal-to-noise ratio (SNR) is above 17.5 dB using our proposed
      FOE technique. However, the error probability of traditional FFT-FOE scheme for
      32-QAM is always intolerant. Finally, our proposed FOE scheme functions well for
      10 Gbaud dual polarization (DP)-32-QAM signal to reach 20% forward error
      correction (FEC) threshold of BER=2*10<sup>-2</sup>, under the scenario of back
      to-back (B2B) transmission.

PMID- 28437959
TI  - High-average-power, 2-MUm femtosecond optical parametric oscillator synchronously
      pumped by a thin-disk, mode-locked laser.
AB  - A high-energy, extended-cavity femtosecond BiBO optical parametric oscillator
      synchronously pumped by a 1.0-ps, 1030-nm Yb:YAG, thin-disk pump laser is
      presented. The oscillator operated near degeneracy in a noncollinear interaction
      geometry, producing signal wavelength tunability from 1.99 to 2.20 MUm. The
      signal pulses have an average power exceeding 2 W, producing 455-fs pulses at
      7.08 MHz with energies up to 350 nJ, showing increased potential for tunable
      sources of scalable ultrafast pulses in the infrared.

PMID- 28437960
TI  - Wind ranging and velocimetry with low peak power and long-duration modulated
      laser.
AB  - A novel approach to simultaneous wind ranging and velocimetry using low peak
      power, long-duration modulated laser pulse transmissions is proposed. Received
      signals backscattered by aerosol particles are processed by a multi-reference
      matched-filter (MRMF) which performs matched filter processing between the
      received signal and several reference signals in parallel and outputs a range
      velocity profile of received power. Ranging and velocimetry are performed
      simultaneously by estimating received power, radial velocity, and velocity
      dispersion from a velocity profile at an arbitrary range in the range-velocity
      profile. The accuracies of the three estimates improve in proportion to the
      square root of pulse duration; that is, a 100 times longer pulse is equivalent to
      a 10-dB amplification.

PMID- 28437961
TI  - Novel asymmetric cryptosystem based on distorted wavefront beam illumination and
      double-random phase encoding.
AB  - Herein, we propose a new security enhancing method that employs wavefront
      aberrations as optical keys to improve the resistance capabilities of
      conventional double-random phase encoding (DRPE) optical cryptosystems. This
      study has two main innovations. First, we exploit a special beam-expander afocal
      reflecting to produce different types of aberrations, and the wavefront
      distortion can be altered by changing the shape of the afocal-reflecting system
      using a deformable mirror. Then, we reconstruct the wavefront aberrations via the
      surface fitting of Zernike polynomials and use the reconstructed aberrations as
      novel asymmetric vector keys. The ideal wavefront and the distorted wavefront
      obtained by wavefront sensing can be regarded as a pair of private and public
      keys. The wavelength and focal length of the Fourier lens can be used as
      additional keys to increase the number of degrees of freedom. This novel
      cryptosystem can enhance the resistance to various attacks aimed at DRPE systems.
      Finally, we conduct ZEMAX and MATLAB simulations to demonstrate the superiority
      of this method.

PMID- 28437962
TI  - Rapidly reconfigurable high-fidelity optical arbitrary waveform generation in
      heterogeneous photonic integrated circuits.
AB  - This paper demonstrates rapidly reconfigurable, high-fidelity optical arbitrary
      waveform generation (OAWG) in a heterogeneous photonic integrated circuit (PIC).
      The heterogeneous PIC combines advantages of high-speed indium phosphide (InP)
      modulators and low-loss, high-contrast silicon nitride
      (Si<sub>3</sub>N<sub>4</sub>) arrayed waveguide gratings (AWGs) so that high
      fidelity optical waveform syntheses with rapid waveform updates are possible. The
      generated optical waveforms spanned a 160 GHz spectral bandwidth starting from an
      optical frequency comb consisting of eight comb lines separated by 20 GHz channel
      spacing. The Error Vector Magnitude (EVM) values of the generated waveforms were
      approximately 16.4%. The OAWG module can rapidly and arbitrarily reconfigure
      waveforms upon every pulse arriving at 2 ns repetition time. The result of this
      work indicates the feasibility of truly dynamic optical arbitrary waveform
      generation where the reconfiguration rate or the modulator bandwidth must exceed
      the channel spacing of the AWG and the optical frequency comb.

PMID- 28437963
TI  - Raman gain and femtosecond laser induced damage of Ge-As-S chalcogenide glasses.
AB  - Chemical stoichiometric Ge-As-S glasses were prepared, and their thermal
      properties, refractive index (n), optical bandgap, Raman gain, and femtosecond
      laser damage were examined. Results revealed that the n and density (rho) of the
      glasses decreased as Ge concentration increased, whereas the bandgap and glass
      transition temperature (Tg) increased. The Raman gain coefficients
      (g<sub>R</sub>) of the samples were calculated on the basis of spontaneous Raman
      scattering spectra. g<sub>R</sub> decreased from 2.79 * 10<sup>-11</sup> m/W for
      As<sub>2</sub>S<sub>3</sub> to 1.06 * 10<sup>-11</sup> m/W for GeS<sub>2</sub> as
      Ge concentration increased. However, the smallest g<sub>R</sub> was 100 times
      higher than that of fused silica (0.89 * 10<sup>-13</sup> m/W). When these
      glasses were irradiated by a laser with a pulse width of 150 fs and a power of 33
      mW at 3 MUm, the damaged area and depth decreased and the damage threshold
      increased gradually as Ge concentration increased. Raman spectra and composition
      analysis indicated that surface oxidation probably occurred and sulfur gasified
      at a high laser power. Although the g<sub>R</sub> decreased as Ge was added, the
      laser damage threshold of Ge-As-S glasses was higher than that of the
      As<sub>2</sub>S<sub>3</sub> glass. Thus, these glasses are potential materials
      for Raman gain media.

PMID- 28437964
TI  - Passively-coupled, low-coherence interferometric duct profiling with an
      astigmatism-corrected conical mirror.
AB  - Duct-profiling in test samples up to 25 mm in diameter has been demonstrated
      using a passive, low-coherence probe head with a depth resolution of 7.8 MUm,
      incorporating an optical-fibre-linked conical mirror addressed by a custom-built
      array of single-mode fibres. Zemax modelling, and experimental assessment of
      instrument performance, show that degradation of focus, resulting from
      astigmatism introduced by the conical mirror, is mitigated by the introduction of
      a novel lens element. This enables a good beam focus to be achieved at distances
      of tens of millimetres from the cone axis, not achievable when the cone is used
      alone. Incorporation of the additional lens element is shown to provide a four
      fold improvement in lateral imaging resolution, when compared with reflection
      from the conical mirror alone.

PMID- 28437965
TI  - Comparison between optical bistabilities versus power and frequency in a
      composite cavity-atom system.
AB  - By making use of the changes in optical properties such as absorption and
      dispersion around the resonance generated via electromagnetically induced
      transparency (EIT), we theoretically and experimentally investigate a "infinity"
      shape optical bistability (OB) versus frequency on the probe transmission with a
      Lambda-shape EIT window in a rubidium atomic ensemble confined in a three-mirror
      optical ring cavity. Compared to the traditional OB reflected by a hysteresis
      loop versus power, such newly demonstrated optical bistable behavior (represented
      by a "infinity"-shape non-overlapping region) by scanning probe and cavity
      detuning can experience dual bistabilities and be more sensitive to the change of
      experimental parameters. Further, we study the relationship between vacuum Rabi
      splitting and the "infinity"-shape OB. Such study on frequency-induced OB could
      effectively improve the applications related to OB such as logic-gate devices and
      optical information processing.

PMID- 28437966
TI  - Energy scaling and extended tunability of terahertz wave parametric oscillator
      with MgO-doped near-stoichiometric LiNbO<sub>3</sub> crystal.
AB  - A widely tunable, high-energy terahertz wave parametric oscillator based on 1
      mol. % MgO-doped near-stoichiometric LiNbO<sub>3</sub> crystal has been
      demonstrated with 1064 nm nanosecond pulsed laser pumping. The tunable range of
      1.16 to 4.64 THz was achieved. The maximum THz wave output energy of 17.49 MUJ
      was obtained at 1.88 THz under the pump energy of 165 mJ/pulse, corresponding to
      the THz wave conversion efficiency of 1.06 * 10<sup>-4</sup> and the photon
      conversion efficiency of 1.59%, respectively. Moreover, under the same
      experimental conditions, the THz output energy of TPO with MgO:SLN crystal was
      about 2.75 times larger than that obtained from the MgO:CLN TPO at 1.60 THz.
      Based on the theoretical analysis, the THz energy enhancement mechanism in the
      MgO:SLN TPO was clarified to originate from its larger Raman scattering cross
      section and smaller absorption coefficient.

PMID- 28437967
TI  - Design of see-through near-eye display for presbyopia.
AB  - We propose a compact design of see-through near-eye display that is dedicated to
      presbyopia. Our solution is characterized by a plano-convex waveguide, which is
      essentially an integration of a corrective lens and two volume holograms. Its
      design rules are set forth in detail, followed by the results and discussion
      regarding the diffraction efficiency, field of view, modulation transfer
      function, distortion, and simulated imaging.

PMID- 28437968
TI  - Vortex energy flows generated by core-shell nanospheres.
AB  - Investigated in this paper is the interaction of light and the nanospheres
      composed by a dielectric core with a gold-shell cladding that causes the optical
      vortices inside the core and the whirlpools around the shell. Different radius
      ratios, dimensions and the dielectric functions of nanospheres were studied using
      the finite-difference time-domain method. It was found that optical vortices were
      most likely to occur in the regions of increased absorption cross section and
      reduced scattering cross section. Two optical vortices of the opposite polarity,
      each centered in one of the particles of a dimer are created by a nanoshell
      dimer. The surrounding media of a nanoshell with different dielectric functions
      can be used to affect the energy flows generated by core-shell nanospheres.

PMID- 28437969
TI  - Experimental generation of complex optical fields for diffraction limited optical
      focus with purely transverse spin angular momentum.
AB  - We demonstrate a method to generate complex optical fields at the pupil plane of
      a high numerical aperture (NA) objective lens for the creation of diffraction
      limited optical focus with purely transverse spin angular momentum. The complex
      optical fields are analytically deduced through reversing the radiated patterns
      from two electric dipoles, which are located at the focal point of the high NA
      lens and oscillate respectively in x- and z- directions with phase difference of
      pi/2. The derived fields can be experimentally created with a vectorial optical
      field generator. Using the Richard-Wolf vectorial diffraction theory, the
      electric fields within the focal region are calculated to evaluate the
      intensities and polarization distributions of the tightly focused beams
      corresponding to both the theoretical and experimentally generated pupil fields
      and the results clearly demonstrate the validity of the proposed technique.

PMID- 28437970
TI  - CMOS-compatible broadband co-propagative stationary Fourier transform
      spectrometer integrated on a silicon nitride photonics platform.
AB  - We demonstrate a novel type of Fourier Transform Spectrometer (FTS) that can be
      realized with CMOS compatible fabrication techniques. This FTS contains no moving
      components and is based on the direct detection of the interferogram generated by
      the interference of the evanescent fields of two co-propagating waveguide modes.
      The theoretical analysis indicates that this type of FTS inherently has a large
      bandwidth (>100 nm). The first prototype that is integrated on a
      Si<sub>3</sub>N<sub>4</sub> waveguide platform is demonstrated and has an
      extremely small size (0.1 mm<sup>2</sup>). We introduce the operation principle
      and report on the preliminary experiments. The results show a moderately high
      resolution (6 nm) which is in good agreement with the theoretical prediction.

PMID- 28437971
TI  - Energy-efficient on-chip optical diode based on the optomechanical effect.
AB  - We propose and experimentally demonstrate an energy-efficient optical diode based
      on the optomechanical effect. The optical signals could transmit during forward
      propagation while be blocked during backward propagation. When launching optical
      signal with a low power of 4.0 mW, the maximum resonance red-shift of the
      asymmetric silicon microring resonator (MRR) could be up to 0.74 nm, in this
      case, a forward-backward nonreciprocal transmission ratio (NTR) of 12.7 dB has
      been achieved. The 10-dB and 5-dB operation bandwidths are 0.08 nm and 0.24 nm,
      respectively. The operating bandwidth could be continuously tuned theoretically
      by changing the input power.

PMID- 28437972
TI  - Integration of bow-tie plasmonic nano-antennas on tapered fibers.
AB  - In this article, a new and flexible approach to control the electric field
      enhancement of bow-tie nano-antennas by integrating them on the lateral of a
      tapered optical fiber is proposed. The device is driven by a Q-switched laser and
      the performance of a fabricated nano-antenna in a quartz slide is tested by a
      Surface Enhanced Raman Scattering (SERS) experiment. A refractive index sensing
      experiment is also performed and a sensitivity of (240 +/- 30) nm/RIU is found in
      the 1.33-1.35 index range.

PMID- 28437973
TI  - 1867-2010 nm tunable femtosecond thulium-doped all-fiber laser.
AB  - We propose and demonstrate a broadly wavelength tunable mode-locked thulium-doped
      all-fiber laser, delivering sub-400 femtosecond (fs) pulses and tuning from 1867
      nm to 2010 nm. The tunable range of 143 nm, to our best knowledge, is the widest
      in the femtosecond mode-locked thulium-doped fiber lasers (TDFLs). The broadly
      tunable range and femtosecond pulse oscillation attribute to the large free
      spectral range and bandwidth of the fiber-based Lyot filter, benefiting from the
      hybrid device based compact configuration. The hybrid device, integrating
      wavelength-division-multiplexer, polarization-sensitive isolator and output
      coupler, effectively diminishes the birefringence and net dispersion.

PMID- 28437974
TI  - Efficient reversible phase mask for TiO<sub>2</sub> submicron gratings directly
      printed on cylindrical surfaces.
AB  - In this article we present a radial phase mask specially designed and
      manufactured for direct micro-structuration under UV photolithography of a
      cylindrical surface covered by a photoresist TiO<sub>2</sub> film. The period of
      the phase mask is sub-micron (between 480 nm and 720 nm) and allows direct
      printing on several types of cylindrical components. With this dedicated
      reversible phase mask we have demonstrated the feasibility of a TiO<sub>2</sub>
      grating with a period of 960 nm, printed on a SiO<sub>2</sub> cylinder or inside
      a SiO<sub>2</sub> tube of 8 mm diameter.

PMID- 28437975
TI  - Experimental demonstration of efficient quantum state tomography of matrix
      product states.
AB  - Quantum state tomography is a key technology for fully determining a quantum
      state. Unfortunately, standard quantum state tomography is intractable for
      general many-body quantum states, because the number of measurements and the post
      processing time increase exponentially with the size of the system. However, for
      the matrix product states (MPSs), there exists an efficient method using linearly
      scaled local measurements and polynomially scaled post-processing times. In this
      study, we demonstrate the validity of the method in practice by reconstructing a
      four-photon MPS from its local two- or three-photon reduced-density matrices with
      the presence of statistical errors and systematical errors in experiment.

PMID- 28437976
TI  - Excitation of Bloch surface wave on tapered fiber coated with one-dimensional
      photonic crystal for refractive index sensing.
AB  - We have theoretically and experimentally demonstrated a novel approach to excite
      Bloch surface wave (BSW) on tapered optical fibers, which are coated with one
      dimensional photonic crystal (1DPC) consisting of periodic TiO<sub>2</sub> and
      Al<sub>2</sub>O<sub>3</sub> by atomic layer deposition technology. Two resonant
      dips are found in transmission spectra that are originated from the excitation of
      BSW for p-polarized light and s-polarized light, respectively. For the first
      time, we have demonstrated the developed device for refractive index (RI)
      sensing.

PMID- 28437977
TI  - Polymer optical fiber Bragg grating inscription with a single UV laser pulse.
AB  - We experimentally demonstrate the first polymer optical fiber Bragg grating
      inscribed with only one krypton fluoride laser pulse. The device has been
      recorded in a single-mode poly(methyl methacrylate) optical fiber, with a core
      doped with benzyl dimethyl ketal for photosensitivity enhancement. One laser
      pulse with a duration of 15 ns, which provide energy density of 974
      mJ/cm<sup>2</sup>, is adequate to introduce a refractive index change of
      0.74*10<sup>-4</sup> in the fiber core. After the exposure, the reflectivity of
      the grating increases for a few minutes following a second order exponential
      saturation. The produced Bragg grating structure rejects 17.9 dB transmitted
      power, thus providing 98.4% reflectivity, which is well suited for sensing
      applications. In addition, we report the importance of the fiber thermal
      treatment before or after the inscription, showing its effects on the lifetime
      and quality of the grating structures. Optimizing the irradiation conditions and
      the material chemical composition, a higher refractive index change in the fiber
      core is feasible. This demonstration significantly improves the potential for
      commercial exploitation of the technology.

PMID- 28437978
TI  - Tunable optical cage array generated by Dammann vector beam.
AB  - Optical cages attract considerable attentions recently owing to their potential
      applications in optical trapping, optical imaging and optical cloaking. However,
      the generation of tunable optical cage arrays in the transverse plane comes to a
      great challenge, which restricts the effectiveness of the above applications. In
      this work, we propose a full polarization-controlled method that optical cage
      arrays with tunable number and positions in the x-y plane can be generated by a
      so-called Dammann vector beam (DVB), both under the conditions of high- and low
      NA focusing system. By adjusting the polarization state of the DVB with the phase
      of Dammann grating, the number and positions of optical cages can be adjusted
      flexibly. This work reveals the relationship between the complex polarization
      state of an incident vector beam and the output optical cage array in the focal
      region, and may find valuable applications in optical imaging, optical trapping,
      etc.

PMID- 28437979
TI  - 30-Hz relative linewidth watt output power 1.65 um continuous-wave singly
      resonant optical parametric oscillator.
AB  - We built a 1-watt cw singly resonant optical parametric oscillator operating at
      an idler wavelength of 1.65 um for application to quantum interfaces. The non
      resonant idler is frequency stabilized by side-fringe locking on a relatively
      high-finesse Fabry-Perot cavity, and the influence of intensity noise is
      carefully analyzed. A relative linewidth down to the sub-kHz level (about 30 Hz
      over 2 s) is achieved. A very good long term stability is obtained for both
      frequency and intensity.

PMID- 28437980
TI  - Angle resolved transmission through metal hole gratings.
AB  - We present the first angle resolved measurements of extraordinary optical
      transmission (EOT) through hole array gratings in a gold film. Varying the
      lattice spacing of the arrays and looking at higher diffraction orders, we
      retrieve the angular emission pattern of the constituent holes with better signal
      to noise ratio than with single-hole experiments. We present a method to
      determine separately the angular dependence of the direct and resonant
      contribution to EOT by using the spectral features of the diffraction orders
      together with an established model. The comparison of our results with the known
      angular transmission of a single hole in a metal film yields a good agreement for
      s-polarized light. Deviations are found for illumination with p-polarized light
      and we address the discrepancy with Coupled Mode Model calculations and Finite
      Difference Time Domain simulations. These measured deviations are currently not
      fully understood.

PMID- 28437981
TI  - Efficient laser noise reduction method via actively stabilized optical delay
      line.
AB  - We report a fiber laser noise reduction method by locking it to an actively
      stabilized optical delay line, specifically a fiber-based Mach-Zehnder
      interferometer with a 10 km optical fiber spool. The fiber spool is used to
      achieve large arm imbalance. The heterodyne signal of the two arms converts the
      laser noise from the optical domain to several megahertz, and it is used in laser
      noise reduction by a phase-locked loop. An additional phase-locked loop is
      induced in the system to compensate the phase noise due to environmentally
      induced length fluctuations of the optical fiber spool. A major advantage of this
      structure is the efficient reduction of out-of-loop frequency noise, particularly
      at low Fourier frequency. The frequency noise reaches -30 dBc/Hz at 1 Hz, which
      is reduced by more than 90 dB compared with that of the laser in its free-running
      state.

PMID- 28437982
TI  - Versatile supercontinuum generation in parabolic multimode optical fibers.
AB  - We demonstrate that the pump's spatial input profile can provide additional
      degrees of freedom in tailoring at will the nonlinear dynamics and the ensuing
      spectral content of supercontinuum generation in highly multimoded optical
      fibers. Experiments and simulations carried out at 1550 nm indicate that the
      modal composition of the input beam can substantially alter the soliton fission
      process as well as the resulting Raman and dispersive wave generation that
      eventually lead to supercontinuum in such a multimode environment. Given the
      multitude of conceivable initial conditions, our results suggest that it is
      possible to pre-engineer the supercontinuum spectral content in a versatile
      manner.

PMID- 28437983
TI  - Generation of patterned-phase-only holograms (PPOHs).
AB  - A fast and non-iterative method for generating a phase-only hologram, hereafter
      referred to as the patterned-phase-only hologram (PPOH), is reported in this
      paper. Briefly, a phase mask with a periodic phase pattern is added to the source
      image, and converted into a hologram. Subsequently, only the phase component is
      retained as a phase-only hologram. Experimental evaluation reveals that the
      visual quality of the reconstructed images of the PPOH generated with our
      proposed method is favorable, and superior to that obtained with existing
      methods.

PMID- 28437984
TI  - Light bullets in coupled nonlinear Schrodinger equations with variable
      coefficients and a trapping potential.
AB  - We analyze three-dimensional (3D) vector solitary waves in a system of coupled
      nonlinear Schrodinger equations with spatially modulated diffraction and
      nonlinearity, under action of a composite self-consistent trapping potential.
      Exact vector solitary waves, or light bullets (LBs), are found using the self
      similarity method. The stability of vortex 3D LB pairs is examined by direct
      numerical simulations; the results show that only low-order vortex soliton pairs
      with the mode parameter values n <= 1, l <= 1 and m = 0 can be supported by the
      spatially modulated interaction in the composite trap. Higher-order LBs are found
      unstable over prolonged distances.

PMID- 28437985
TI  - Scattering of surface plasmon polaritons at a planar interface by an embedded
      dielectric nanocube.
AB  - We investigate scattering of surface plasmon polaritons (SPPs) at a planar metal
      dielectric interface by a dielectric nanocube embedded in the metal layer using
      finite element method-based simulations. The scattering characteristics of the
      embedded nanocube, such as the scattering and absorption cross sections, far
      field scattering patterns, reflectance, and transmittance, are calculated as
      functions of the wavelength of the incident SPP waves in the visible range. The
      main features of the characteristics are explained in connection with the
      excitation of plasmonic eigenmodes of the embedded nanocube. The most efficient
      scattering into waves propagating away from the metal surface, i.e., the
      radiating modes, occurs when a dipolar-like plasmonic mode is excited, whose
      eigenfrequency can be tuned by changing the edge length of the nanocube.

PMID- 28437986
TI  - Control and design heat flux bending in thermal devices with transformation
      optics.
AB  - We propose a fundamental latent function of control heat transfer and heat flux
      density vectors at random positions on thermal materials by applying
      transformation optics. The expressions for heat flux bending are obtained, and
      the factors influencing them are investigated in both 2D and 3D cloaking schemes.
      Under certain conditions, more than one degree of freedom of heat flux bending
      exists corresponding to the temperature gradients of the 3D domain. The heat flux
      path can be controlled in random space based on the geometrical azimuths, radial
      positions, and thermal conductivity ratios of the selected materials.

PMID- 28437987
TI  - Source diversity for transport of intensity phase imaging.
AB  - The transport of intensity equation (TIE) is a phase retrieval method that relies
      on measurements of the intensity of a paraxial field under propagation between
      two or more closely spaced planes. A limitation of TIE is its susceptibility to
      low frequency noise artifacts in the reconstructed phase. Under Kohler
      illumination, when both illumination power and exposure time are limited, the use
      of larger sources can improve low-frequency performance although it introduces
      blurring. Appropriately combining intensity measurements taken with a diversity
      of source sizes can improve both low- and high-frequency performance in phase
      reconstruction.

PMID- 28437989
TI  - Low-loss, compact, and fabrication-tolerant Si-wire 90 degrees  waveguide bend
      using clothoid and normal curves for large scale photonic integrated circuits.
AB  - Ultimately low-loss 90 degrees  waveguide bend composed of clothoid and normal
      curves is proposed for dense optical interconnect photonic integrated circuits.
      By using clothoid curves at the input and output of 90 degrees  waveguide bend,
      straight and bent waveguides are smoothly connected without increasing the
      footprint. We found that there is an optimum ratio of clothoid curves in the bend
      and the bending loss can be significantly reduced compared with normal bend. 90%
      reduction of the bending loss for the bending radius of 4 MUm is experimentally
      demonstrated with excellent agreement between theory and experiment. The
      performance is compared with the waveguide bend with offset, and the proposed
      bend is superior to the waveguide bend with offset in terms of fabrication
      tolerance.

PMID- 28437988
TI  - Selective excitation of surface plasmon modes propagating in Ag nanowires.
AB  - Surface plasmon modes propagating in metal nanowires are conveniently excited by
      focusing a laser beam on one extremity of the nanowire. We find that the precise
      positioning of the nanowire inside the focal region drastically influences the
      excitation efficiency of the different SPP modes sustained by the plasmonic
      waveguide. We demonstrate a spatially selective excitation of bound and leaky
      surface plasmon modes with excitation maps that strongly depend on the
      orientation of the incident linear polarization. We discuss this modal selection
      by considering the inhomogeneous distribution of the field components inside the
      focus. Our finding provides a way to discriminate the effective indices of the
      modes offering thus an increased coupling agility for future nanowire-based
      plasmonic architectures.

PMID- 28437990
TI  - Silicon mode (de)multiplexers with parameters optimized using shortcuts to
      adiabaticity.
AB  - We propose and experimentally demonstrate broadband silicon mode (de)multiplexers
      based on the optimization of system adiabaticity using shortcuts to adiabaticity
      (STA). The measured insertion losses and crosstalks were less than 1.1 dB and -24
      dB, respectively, for the five two-mode mode-division-multiplexing (MDM) links
      over wavelengths ranging from 1500 nm to 1600 nm. The four-mode MDM link showed
      measured insertion losses and crosstalks less than 1.3 dB and -23 dB,
      respectively, within the same wavelength range. The method paves the way for
      future adaptation of the STA protocols to various components.

PMID- 28437991
TI  - High-speed triangular pattern phase-shifting 3D measurement based on the motion
      blur method.
AB  - Recent advancements in 3D measurement technologies have increased the urgency of
      requiring high-speed 3D measurement in many fields. This study presents a novel
      four-step triangular pattern phase-shifting 3D measurement using the motion blur
      method, which combines the advantages of phase-shifting methods. To comply with
      the high speed requirement, binary coded triangular patterns are projected and
      could dither vertically. Therefore, the image captured by the camera is blurred
      into grayscale-intensity triangular patterns, which can be used for phase
      unwrapping and 3D reconstruction. The proposed method decreased the projection
      time compared with sinusoidal patterns using a DMD (digital micromirror device)
      projector. Furthermore, this study presents a four-step triangular phase-shifting
      unwrapping algorithm. The experiments indicate that the proposed method can
      achieve high-speed 3D measurement and reconstruction.

PMID- 28437992
TI  - A large airborne survey of Earth's visible-infrared spectral dimensionality.
AB  - The intrinsic spectral dimensionality indicates the observable degrees of freedom
      in Earth's solar-reflected light field, quantifying the diversity of spectral
      content accessible by visible and infrared remote sensing. The solar-reflected
      regime spans the 0.38 - 2.5 MUm interval, and is captured by a wide range of
      current and planned instruments on both airborne and orbital platforms. To date
      there has been no systematic study of its spectral dimensionality as a function
      of space, time, and land cover. Here we report a multi-site, multi-year
      statistical survey by NASA's "Classic" Airborne Visible Near InfraRed
      Spectrometer (AVIRIS-C). AVIRIS-C measured large regions of California, USA,
      spanning wide latitudinal and elevation gradients containing all canonical MODIS
      land cover types. The spectral uniformity of the AVIRIS-C design enabled
      consistent in-scene assessment of measurement noise across acquisitions. The
      estimated dimensionality as a function of cover type ranged from the low 20s to
      the high 40s, and was approximately 50 for the combined dataset. This result
      indicates the high diversity of physical processes distinguishable by imaging
      spectrometers like AVIRIS-C for one region of the Earth.

PMID- 28437993
TI  - Integrated optical force sensors using focusing photonic crystal arrays.
AB  - Mechanical oscillators are at the heart of many sensor applications. Recently
      several groups have developed oscillators that are probed optically, fabricated
      from high-stress silicon nitride films. They exhibit outstanding force
      sensitivities of a few aN/Hz<sup>1/2</sup> and can also be made highly
      reflective, for efficient detection. The optical read-out usually requires
      complex experimental setups, including positioning stages and bulky cavities,
      making them impractical for real applications. In this paper we propose a novel
      way of building fully integrated all-optical force sensors based on low-loss
      silicon nitride mechanical resonators with a photonic crystal reflector. We can
      circumvent previous limitations in stability and complexity by simulating a
      suspended focusing photonic crystal, purely made of silicon nitride. Our design
      allows for an all integrated sensor, built out of a single block that integrates
      a full Fabry-Perot cavity, without the need for assembly or alignment. The
      presented simulations will allow for a radical simplification of sensors based on
      high-Q silicon nitride membranes. Our results comprise, to the best of our
      knowledge, the first simulations of a focusing mirror made from a mechanically
      suspended flat membrane with subwavelength thickness. Cavity lengths between a
      few hundred um and mm should be directly realizable.

PMID- 28437994
TI  - High-speed asynchronous optical sampling based on GHz Yb:KYW oscillators.
AB  - A low-cost scheme of high-speed asynchronous optical sampling based on Yb:KYW
      oscillators is reported. Two GHz diode-pumped oscillators with a slight pulse
      repetition rate offset serve as pump and probe source, respectively. The temporal
      resolution of this system is limited to 500 fs mainly by the pulse duration of
      the oscillators and also by relative timing jitter between the oscillators. A
      near-shot-noise noise floor around 10<sup>-6</sup> (?R/R) is obtained within a
      data acquisition time of a few seconds. The performance of the system is
      demonstrated by measurements of coherent acoustic phonons in a semiconductor
      sample that resembles a semiconductor saturable absorber mirror or an optically
      pumped semiconductor chip.

PMID- 28437995
TI  - Single-measurement digital optical frequency comb based phase-detection Brillouin
      optical time domain analyzer.
AB  - A single-measurement sweep-free distributed Brillouin optical time domain
      analyzer (BOTDA) sensor based on phase detection is proposed and experimentally
      demonstrated employing digital optical frequency comb (DOFC) probe signal.
      Brillouin Phase Spectrum (BPS) of DOFC probe induced by Brillouin interaction is
      measured using coherent detection in a single acquisition, without any frequency
      scanning and data averaging. Single-measurement BOTDA sensor based on BPS in 10km
      long fiber is demonstrated with a response time of 100 MUs, which is limited only
      by the fiber length. The spatial resolution is 51.2m, determined by the duration
      of DOFC. And the Brillouin frequency shift (BFS) uncertainty is estimated to
      be~1.5 MHz at the end of fiber under test (FUT). Benefiting from the fast
      response time, dynamic measurement up to 1 kHz vibration frequency has been
      demonstrated.

PMID- 28437996
TI  - High contrast switchability of VO<sub>2</sub> based metamaterial absorbers with
      ITO ground plane.
AB  - A metamaterial consisting of an array of gold micro-disks, separated from a
      ground plane of indium tin oxide (ITO) by a thin film of vanadium dioxide
      (VO<sub>2</sub>), behaves as a perfect absorber at infrared (IR) frequencies at
      room temperature. This metamaterial, which is transparent to visible light, can
      be switched to a highly reflecting state for IR light by heating the metamaterial
      to temperatures larger than the metal-insulator phase transition temperature 68
      degrees C of VO<sub>2</sub>. For a disk diameter of 1.5 MUm and VO<sub>2</sub>
      film thickness of 320 nm, two absorption bands are obtained: one, that arises
      from the metamaterial resonance; and a second peak that arises principally from a
      Fabry-Perot resonance. A large change (>78%) occurs in the reflectivity between
      the low and high temperature phases. IR emittance of the metamaterial was
      measured with IR cameras and shown to be switchable to result in low emittance at
      high temperature. Optical readout of the state of VO<sub>2</sub> within the
      metamaterial is demonstrated.

PMID- 28437997
TI  - Effect of ZnO nanostructures on the optical properties of white light-emitting
      diodes.
AB  - White light produced by blue LEDs with yellow phosphor is the most widely used
      methods, but it results in poor quality in angular CCT uniformity. In this work,
      a novel technique was introduced to solve this problem by integrating different
      ZnO nanostructures into white light-emitting diodes. The experiment of ZnO doped
      films and the simulation of Finite-Difference Time-Domain (FDTD) were carried
      out. The result indicated scattering effect of ZnO nanoparticles could improve
      uniformity of scattering energy effectively. Moreover, the effect of ZnO
      nanostructures on white light-emitting diodes (wLEDs) devices was also
      investigated. The CCT deviation of wLEDs devices would decrease from 3455.49 K to
      96.30 K, 40.03 K and 60.09 K when the node-like (N-ZnO), sheet-like (S-ZnO) and
      rod-like ZnO (R-ZnO) respectively applied. The higher CCT uniformity and little
      luminous flux dropping were achieved when the optimal concentrations of N-ZnO, S
      ZnO, and R-ZnO nanostructures were 0.25%, 0.75%, and 0.25%. This low-cost and
      green manufacturing method has a great impact on development of white light
      emitting diodes.

PMID- 28437998
TI  - Specific distribution of the light captured by silver nanowire.
AB  - The silver nanowire (AgNW) has excellent light capture ability, showing great
      prospects in many fields. Based on discrete dipole approximation simulations, it
      is found that the captured light can be subdivided into three parts: the near
      field light occupies ~27.3%, mainly confined around the nanowire with a distance
      <20nm; the far-field part occupies ~59.6%, showing a dramatic conical
      distribution; and ~13.1% is ohmically absorbed. These insights are helpful to
      estimate the limited performance of AgNW-based device utilizing each subdivision,
      and locate the functional zone. Besides, we found that the light capture
      efficiency of AgNW can be easily controlled as it increases linearly with
      nanowire length.

PMID- 28437999
TI  - Novel programmable microwave photonic filter with arbitrary filtering shape and
      linear phase.
AB  - We propose and demonstrate a novel optical frequency comb (OFC) based microwave
      photonic filter which is able to realize arbitrary filtering shape with linear
      phase response. The shape of filter response is software programmable using
      finite impulse response (FIR) filter design method. By shaping the OFC spectrum
      using a programmable waveshaper, we can realize designed amplitude of FIR taps.
      Positive and negative sign of FIR taps are achieved by balanced photo-detection.
      The double sideband (DSB) modulation and symmetric distribution of filter taps
      are used to maintain the linear phase condition. In the experiment, we realize a
      fully programmable filter in the range from DC to 13.88 GHz. Four basic types of
      filters (lowpass, highpass, bandpass and bandstop) with different bandwidths, cut
      off frequencies and central frequencies are generated. Also a triple-passband
      filter is realized in our experiment. To the best of our knowledge, it is the
      first demonstration of a programmable multiple passband MPF with linear phase
      response. The experiment shows good agreement with the theoretical result.

PMID- 28438000
TI  - Development of limited-view and three-dimensional reconstruction method for
      analysis of electrohydrodynamic jetting behavior.
AB  - For an electrohydrodynamic (EHD) jet, variables such as the direction of the
      meniscus and the ejection stability need to be analyzed. Thus, the EHD jet should
      be observed three-dimensionally (3D) because the variables can only be obtained
      in the 3D field, especially in unstable modes. However, if the 3D field is
      reconstructed from multi-directional binary images, eliminating reconstruction
      errors caused by invisible areas is almost impossible, even when using a
      tomographic technique. To solve this problem, a new 3D reconstruction method
      including an ellipse estimation was developed in this study. The method was
      verified by numerical simulation and applied to estimate the jetting flow rate
      and the direction of an ethanol droplet ejected from a nozzle according to a
      voltage.

PMID- 28438001
TI  - Noise reduction in third order cross-correlation by angle optimization of the
      interacting beams.
AB  - We report on a novel technique to reduce the noise level in scanning third order
      cross-correlation. Large angles between the interacting beams combined with
      adapted crystal parameters lead to a significant decrease of noise photon
      generation while maintaining efficient generation of the third order signal. An
      enhanced scanning cross-correlator was developed based on the new technique
      proposed. In tests at the PHELIX laser facility this novel correlator performed
      within a dynamic range of 12.5 orders of magnitude.

PMID- 28438002
TI  - Hot luminescence from gold nanoflowers and its application in high-density
      optical data storage.
AB  - Gold nanoflowers with feature sizes ranging from several tenths to several
      hundred nanometers were synthesized by using the one-pot method. They were formed
      by the self-organization of gold nanoparticles of several nanometers and
      exhibited broad extinction spectra in the near infrared spectral range. Randomly
      distributed hot spots originating from the strongly localized modes were
      generated in gold nanoflowers and their appearances exhibited strong dependences
      on both the polarization and wavelength of the excitation light. Under the
      excitation of femtosecond laser pulses, such hot spots emitted efficient hot
      luminescence spanning the visible to near infrared spectral range. Distinct from
      the hot luminescence of single hot spots formed on rough gold and silver
      surfaces, the hot luminescence from gold nanoflowers composed of a large number
      of hot spots exhibited excitation-intensity dependence quite similar to the
      emission spectrum. It was demonstrated that the polarization- and wavelength
      dependent hot luminescence of gold nanoflowers can be utilized to realize optical
      data storage with high density and low energy.

PMID- 28438003
TI  - Wavelength multicasting through four-wave mixing with an optical comb source.
AB  - Based on four-wave mixing (FWM) with an optical comb source (OCS), we
      experimentally demonstrate 26-way or 15-way wavelength multicasting of 10-Gb/s
      differential phase-shift keying (DPSK) data in a highly-nonlinear fiber (HNLF) or
      a silicon waveguide, respectively. The OCS provides multiple spectrally
      equidistant pump waves leading to a multitude of FWM products after mixing with
      the signal. We achieve error-free operation with power penalties less than 5.7 dB
      for the HNLF and 4.2 dB for the silicon waveguide, respectively.

PMID- 28438004
TI  - Autofocusing Airy beams generated by all-dielectric metasurface for visible
      light.
AB  - Conventional method to generate autofocusing Airy (AFA) beam involves the optical
      Fourier transform (FT) system, which has a fairly long working distance due to
      the focal length of FT lens, presence of spatial light modulator (SLM) and
      auxiliary total reflection mirrors. Here, we propose an extremely compact design
      to generate high-efficiency AFA beam at visible frequency by using metasurface
      which is composed of a single layer array of amorphous titanium dioxide
      (TiO<sub>2</sub>) elliptical nanofins sitting on the fused-silica substrate.
      Numerical simulations show that the designed structures are capable of precisely
      controlling the deflection of Airy beam and tuning the focal length of AFA beam.
      We further numerically demonstrate that the phase modulation of AFA beam could
      combine with the concept of vortex light field to produce vortical AFA beam. We
      anticipate that such device can be useful in the ultra-compact integrated optic
      system, biomedical nanosurgery and optical trapping applications.

PMID- 28438005
TI  - Comparative studies on the quality factors of whispering gallery modes and hybrid
      plasmon photon modes.
AB  - We theoretically and experimentally investigate the multipolar hybrid plasmon
      photon modes supported by a dielectric-metal core-shell resonator consisting of a
      dielectric core wrapped by a thin silver shell and the whispering-gallery modes
      in its pure dielectric counterpart (the dielectric sphere with the same size). We
      theoretically demonstrate that in a certain wavelength range the achievable
      maximum Q-factors of hybrid modes could be either larger or smaller than that of
      whispering-gallery modes, depending on the size of the resonator. By means of the
      coupling of the dye molecules to the hybrid and whispering-gallery modes, the
      reshaped fluorescence spectra are measured for resonators containing two
      different sized dye-doped dielectric spheres, which allow us to compare the Q
      factors of hybrid and whispering-gallery modes, providing direct experimental
      support to the theoretical predictions. Our results provide guidance for
      appropriately choosing plasmonic core-shell (hybrid modes) or dielectric
      resonators (whispering-gallery modes) in applications such as ultrasensitive bio
      sensors, low-threshold lasing, slow-light and nonlinear optical devices.

PMID- 28438006
TI  - Measurements and modeling of multipath interference at wavelengths below cable
      cut-off in a G.654 optical fiber span.
AB  - Transmission below the cable cut-off wavelength may be a concern in some systems,
      especially for an optical supervisory channel (OSC) operating below the signal
      transmission band in systems built with G.654 fiber. In this work, we constructed
      a cabled span of G.654-compliant fiber and measured the multipath interference
      (MPI) generated during propagation through the span at a range of wavelengths
      below the cable cut-offs of the constituent fibers. Measurements were made under
      a range of conditions including different splice losses and the presence or
      absence of higher order mode filters placed around the splices. MPI levels were
      found to be sufficiently low at wavelengths far below the average cable cut-off
      such that OSC transmission was penalty-free. We compare the experimental results
      to modeling predictions and find very good agreement.

PMID- 28438007
TI  - High speed cleaving of crystals with ultrafast Bessel beams.
AB  - We develop a novel concept for ultra-high speed cleaving of crystalline materials
      with femtosecond lasers. Using Bessel beams in single shot, fracture planes can
      be induced nearly all along the Bessel zone in sapphire. For the first time, we
      show that only for a pulse duration below 650 fs, a single fracture can be
      induced in sapphire, while above this duration, cracks appear in all
      crystallographic orientations. We determine the influential parameters which are
      polarization direction, crystallographic axes and scanning direction. This is
      applied to cleave sapphire with a spacing as high as 25 MUm between laser
      impacts.

PMID- 28438008
TI  - Birefringent masks that are optimal for generating bottle fields.
AB  - An optical bottle field containing a three-dimensional intensity null at the
      focal point can be generated by placing a spatially inhomogeneous birefringent
      mask at the pupil of an aplanatic high-NA focusing system. We derive the optimal
      birefringence distribution for which a uniformly polarized input beam is
      converted into a bottle field with the sharpest possible null in intensity. We
      show that a stress engineered optical (SEO) window, which has a radially varying
      retardance, followed by a half-wave plate, performs nearly as well as the optimal
      solution. Experimental results corroborate that an SEO element can be used to
      generate a bottle field.

PMID- 28438009
TI  - Modulation-format-free and automatic bias control for optical IQ modulators based
      on dither-correlation detection.
AB  - A novel automatic bias control (ABC) method for optical in-phase and quadrature
      (IQ) modulator is proposed and experimentally demonstrated. In the proposed
      method, two different low frequency sine wave dither signals are generated and
      added on to the I/Q bias signal respectively. Instead of power monitoring of the
      harmonics of the dither signal, dither-correlation detection is proposed and used
      to adjust the bias voltages of the optical IQ modulator. By this way, not only
      frequency spectral analysis isn't required but also the directional bias
      adjustment could be realized, resulting in the decrease of algorithm complexity
      and the growth of convergence rate of ABC algorithm. The results show that the
      sensitivity of the proposed ABC method outperforms that of the traditional dither
      frequency monitoring method. Moreover, the proposed ABC method is proved to be
      modulation-format-free, and the transmission penalty caused by this method for
      both 10 Gb/s optical QPSK and 17.9 Gb/s optical 16QAM-OFDM signal transmission
      are negligible in our experiment.

PMID- 28438010
TI  - Study on Crystallographic Orientation Effect on Surface Generation of Aluminum in
      Nano-cutting.
AB  - The material characteristics such as size effect are one of the most important
      factors that could not be neglected in cutting the material at nanoscale. The
      effects of anisotropic nature of single crystal materials in nano-cutting are
      investigated employing the molecular dynamics simulation. Results show that the
      size effect of the plastic deformation is based on different plastic carriers,
      such as the twin, stacking faults, and dislocations. The minimum uncut chip
      thickness is dependent on cutting direction, where even a negative value is
      obtained when the cutting direction is {110}<001>. It also determines the
      material deformation and removal mechanism (e.g., shearing, extruding, and
      rubbing mechanism) with a decrease in uncut chip thickness. When material is
      deformed by shearing, the primary shearing zone expands from the stagnation point
      or the tip of stagnation zone. When a material is deformed by extruding and
      rubbing, the primary deformation zone almost parallels to the cutting direction
      and expands from the bottom of the cutting edge merging with the tertiary
      deformation zone. The generated surface quality relates to the crystallographic
      orientation and the minimum uncut chip thickness. The cutting directions of
      {110}<001>, {110}<1-10>, and {111}<1-10>, whose minimum uncut chip thickness is
      relatively small, have better surface qualities compared to the other cutting
      direction.

PMID- 28438011
TI  - Electrical and Optical Properties of Au-Catalyzed GaAs Nanowires Grown on Si
      (111) Substrate by Molecular Beam Epitaxy.
AB  - In this study, defect-free zinc blende GaAs nanowires on Si (111) by molecular
      beam epitaxy (MBE) growth are systematically studied through Au-assisted vapor
      liquid-solid (VLS) method. The morphology, density, and crystal structure of GaAs
      nanowires were investigated as a function of substrate temperature, growth time,
      and As/Ga flux ratio during MBE growth, as well as the thickness, annealing time,
      and annealing temperature of Au film using scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), X-ray diffraction (XRD),
      cathodoluminescence (CL), and Raman spectroscopy. When the As/Ga flux ratio is
      fixed at 25 and the growth temperature at 540  degrees C, the GaAs nanowires
      exhibit a defect-free zinc blende structure with uniform and straight morphology.
      According to the characteristics of GaAs nanowires grown under varied conditions,
      a growth mechanism for defect-free zinc blende GaAs nanowires via Au-assisted
      vapor-liquid-solid (VLS) method is proposed. Finally, doping by Si and Be of
      nanowires is investigated. The results of doping lead to GaAs nanowires
      processing n-type and p-type semiconductor properties and reduced electrical
      resistivity. This study of defect-free zinc blende GaAs nanowire growth should be
      of assistance in further growth and applications studies of complex III-V group
      nanostructures.

PMID- 28438012
TI  - Smartphone-Based Dual-Modality Imaging System for Quantitative Detection of Color
      or Fluorescent Lateral Flow Immunochromatographic Strips.
AB  - Nowadays, lateral flow immunochromatographic assays are increasingly popular as a
      diagnostic tool for point-of-care (POC) test based on their simplicity,
      specificity, and sensitivity. Hence, quantitative detection and pluralistic
      popular application are urgently needed in medical examination. In this study, a
      smartphone-based dual-modality imaging system was developed for quantitative
      detection of color or fluorescent lateral flow test strips, which can be operated
      anywhere at any time. In this system, the white and ultra-violet (UV) light of
      optical device was designed, which was tunable with different strips, and the
      Sobel operator algorithm was used in the software, which could enhance the
      identification ability to recognize the test area from the background boundary
      information. Moreover, this technology based on extraction of the components from
      RGB format (red, green, and blue) of color strips or only red format of the
      fluorescent strips can obviously improve the high-signal intensity and
      sensitivity. Fifty samples were used to evaluate the accuracy of this system, and
      the ideal detection limit was calculated separately from detection of human
      chorionic gonadotropin (HCG) and carcinoembryonic antigen (CEA). The results
      indicated that smartphone-controlled dual-modality imaging system could provide
      various POC diagnoses, which becomes a potential technology for developing the
      next-generation of portable system in the near future.

PMID- 28438013
TI  - Characterization of Newly Bred Cordyceps militaris Strains for Higher Production
      of Cordycepin through HPLC and URP-PCR Analysis.
AB  - Cordyceps militaris, a member of Ascomycota, a mushroom referred to as
      caterpillar Dongchung-ha-cho, is commercially valuable because of its high
      content of bioactive substances, including cordycepin, and its potential for
      artificial cultivation. Cordycepin (3'-deoxyadenosine) is highly associated with
      the pharmacological effects of C. militaris. C. militaris is heterothallic in
      that two mating-type loci, idiomorph MAT1-1 and MAT1-2, exist discretely in two
      different spores. In this study, nine C. militaris strains were mated with each
      other to prepare newly bred strains that produced a larger amount of cordycepin
      than the parent strains. Nine strains of C. militaris were identified by
      comparing the internal transcribed spacer sequence, and a total of 12 single
      spores were isolated from the nine strains of C. militaris. After the MAT
      idiomorph was confirmed by PCR, 36 mating combinations were performed with six
      single spores with MAT1-1 and the others with MAT1-2. Eight mating combinations
      were successfully mated, producing stroma with perithecia. Cordycepin content
      analysis of all strains by high-performance liquid chromatography revealed that
      the KASP4-bred strain produced the maximum cordycepin among all strains,
      regardless of the medium and stroma parts. Finally, universal rice primer-PCR was
      performed to demonstrate that the bred strains were genetically different from
      the parental strains and new C. militaris strains. These results may be related
      to the recombination of genes during mating. The newly produced strains can be
      used to meet the industrial demand for cordycepin. In addition, breeding through
      mating suggests the possibility of producing numerous cordycepin-producing C.
      militaris strains.

PMID- 28438014
TI  - Characterization of a Glutamate Decarboxylase (GAD) from Enterococcus avium M5
      Isolated from Jeotgal, a Korean Fermented Seafood.
AB  - To develop starters for the production of functional foods or materials, lactic
      acid bacteria producing gamma-aminobutyric acid (GABA) were screened from
      jeotgals, Korean fermented seafoods. One isolate producing a high amount of GABA
      from monosodium L-glutamate (MSG) was identified as Enterococcus avium by 16S
      rRNA gene sequencing. E. avium M5 produced 18.47 +/- 1.26 mg/ml GABA when
      incubated for 48 h at 37 degrees C in MRS broth with MSG (3% (w/v)). A gadB gene
      encoding glutamate decarboxylase (GAD) was cloned and overexpressed in E. coli
      BL21 (DE3) using the pET26b (+) expression vector. Recombinant GAD was purified
      through a Ni-NTA column and the size was estimated to be 53 kDa by SDS-PAGE.
      Maximum GAD activity was observed at pH 4.5 and 55 degrees C and the activity was
      dependent on pyridoxal 5'-phosphate. The Km and Vmax values of GAD were 3.26 +/-
      0.21 mM and 0.0120 +/- 0.0001 mM/min, respectively, when MSG was used as a
      substrate. Enterococcus avium M5 secretes a lot of GABA when grown on MRS with
      MSG, and the strain is useful for the production of fermented foods containing a
      high amount of GABA.

PMID- 28438016
TI  - Highly Oriented Low-Dimensional Tin Halide Perovskites with Enhanced Stability
      and Photovoltaic Performance.
AB  - The low toxicity and a near-ideal choice of bandgap make tin perovskite an
      attractive alternative to lead perovskite in low cost solar cells. However, the
      development of Sn perovskite solar cells has been impeded by their extremely poor
      stability when exposed to oxygen. We report low-dimensional Sn perovskites that
      exhibit markedly enhanced air stability in comparison with their 3D counterparts.
      The reduced degradation under air exposure is attributed to the improved
      thermodynamic stability after dimensional reduction, the encapsulating organic
      ligands, and the compact perovskite film preventing oxygen ingress. We then
      explore these highly oriented low-dimensional Sn perovskite films in solar cells.
      The perpendicular growth of the perovskite domains between electrodes allows
      efficient charge carrier transport, leading to power conversion efficiencies of
      5.94% without the requirement of further device structure engineering. We tracked
      the performance of unencapsulated devices over 100 h and found no appreciable
      decay in efficiency. These findings raise the prospects of pure Sn perovskites
      for solar cells application.

PMID- 28438015
TI  - Genome Characteristics of Lactobacillus fermentum Strain JDFM216 for Application
      as Probiotic Bacteria.
AB  - Lactobacillus fermentum strain JDFM216, isolated from a Korean infant feces
      sample, possesses the ability to enhance the longevity and immune response of a
      Caenorhabditis elegans host. To explore the characteristics of strain JDFM216 at
      the genetic level, we performed whole-genome sequencing using the PacBio system.
      The circular draft genome has a total length of 2,076,427 bp and a total of 2,682
      encoding sequences were identified. Five phylogenetically featured genes possibly
      related to the longevity and immune response of the host were identified in L.
      fermentum strain JDFM216. These genes encode UDP-N-acetylglucosamine 1
      carboxyvinyltransferase (E.C. 2.5.1.7), ErfK/YbiS/YcfS/YnhG family protein, site
      specific recombinase XerD, homocysteine S-methyltransferase (E.C. 2.1.1.10), and
      aspartate-ammonia ligase (E.C. 6.3.1.1), which are involved in peptidoglycan
      synthesis and amino acid metabolism in the gut environment. Our findings on the
      genetic background of L. fermentum strain JDFM216 and its potential candidate
      genes for host longevity and immune response provide new insight for the
      application of this strain in the food industry as newly isolated functional
      probiotic.

PMID- 28438017
TI  - Pattern Recognition of Cells via Multiplexed Imaging with Monosaccharide
      Imprinted Quantum Dots.
AB  - Recognition of cancer cells is essential for many important areas such as
      targeted cancer therapy. Multimonosaccharide-based recognition could be a useful
      strategy to improve the recognition specificity, but such a possibility has not
      been explored yet. Herein we report pattern recognition of cells via multiplexed
      imaging with monosaccharide-imprinted quantum dots (QDs). Imprinted with sialic
      acid, fucose, and mannose as the template, respectively, the QDs exhibited good
      specificity toward the template monosaccharides. Multiplexed imaging of cells
      simultaneously stained with these monosaccharide-imprinted QDs revealed the
      relative expression levels of the monosaccharides on the cells. Pattern
      recognition constructed using the intensities of multiplexed imaging unveiled the
      similarities and differences of different cell lines, allowing for the
      recognition of not only cancer cells from normal cells but also cancer cells of
      different cell lines. Thus, this study paved a solid ground for the design and
      preparation of novel cancer-cell targeting reagents and nanoprobes.

PMID- 28438018
TI  - Control of Mechanical Stability of Hollow Silica Particles, and Its Measurement
      by Mercury Intrusion Porosimetry.
AB  - Hollow silica particles (HSPs) have become the focus of interest in many
      laboratories recently, because of their versatility, stemming from the ability to
      control their size and shape, as well as surface functionalization. Determining
      the mechanical stability of hollow particles is essential for their use, both in
      applications in which they need to retain their structure, as well as those in
      which they need to break down. We have synthesized a series of HSPs (inner
      diameter of 231 nm) with increasing wall thickness (7-25 nm), using a template
      approach. Their mechanical stability was measured using mercury intrusion
      porosimetry (MIP), which represents the novel application of the technique for
      these materials. The samples with complete shells break at progressively higher
      pressures, and samples with wall thickness >=21 nm remain stable to the highest
      pressure applied (414 MPa). Other characterization methods, namely microscopy,
      gas adsorption, and small-angle X-ray scattering, shed light on the size
      parameters of the particles, as well as the porosity of the silica walls. By
      varying the amount of silica precursor used in the template coating step, we were
      able to produce hollow silicas with variable stability, thereby allowing for
      control of their mechanical properties.

PMID- 28438019
TI  - l-Phenylalanine-Tethered, Naphthalene Diimide-Based, Aggregation-Induced, Green
      Emitting Organic Nanoparticles.
AB  - The present article delineates the formation of green fluorescent organic
      nanoparticle through supramolecular aggregation of naphthalene diimide (NDI)
      based, carboxybenzyl-protected, l-phenylalanine-appended bola-amphiphile, NDI-1.
      The amphiphilic molecule is soluble in DMSO, and, with gradual addition of water
      within the DMSO solution, the amphiphile starts to self-assemble via H-type
      aggregation to form spherical nanoparticles. These self-assembly of NDI-1 in the
      presence of a high amount of water exhibited aggregation-induced emission (AIE)
      through excimer formation. Notably, in the presence of 99% water content, the
      amphiphile forms spherical aggregated nanoparticles as confirmed from microscopic
      investigations and dynamic light scattering study. Interestingly, the emission
      maxima of molecularly dissolved NDI-1 (weak blue fluorescence) red-shifted upon
      aggregation with increase in water concentration and led to the formation of
      green-emitting fluorescent organic nanoparticles (FONPs) at 99% water content.
      These green-emitting FONPs were utilized in cell imaging as well as for efficient
      transportation of anticancer drug curcumin inside mammalian cells.

PMID- 28438020
TI  - Catalytic Decomposition of Hydroxylammonium Nitrate Ionic Liquid: Enhancement of
      NO Formation.
AB  - Hydroxylammonium nitrate (HAN) is a promising candidate to replace highly toxic
      hydrazine in monopropellant thruster space applications. The reactivity of HAN
      aerosols on heated copper and iridium targets was investigated using tunable
      vacuum ultraviolet photoionization time-of-flight aerosol mass spectrometry. The
      reaction products were identified by their mass-to-charge ratios and their
      ionization energies. Products include NH3, H2O, NO, hydroxylamine (HA), HNO3, and
      a small amount of NO2 at high temperature. No N2O was detected under these
      experimental conditions, despite the fact that N2O is one of the expected
      products according to the generally accepted thermal decomposition mechanism of
      HAN. Upon introduction of iridium catalyst, a significant enhancement of the
      NO/HA ratio was observed. This observation indicates that the formation of NO via
      decomposition of HA is an important pathway in the catalytic decomposition of
      HAN.

PMID- 28438022
TI  - Improvements in Nanoparticle Tracking Analysis To Measure Particle Aggregation
      and Mass Distribution: A Case Study on Engineered Nanomaterial Stability in
      Incineration Landfill Leachates.
AB  - Numerous nanometrology techniques have been developed in recent years to
      determine the size, concentration, and a number of other characteristics of
      engineered nanomaterials (ENM) in environmental matrices. Among the many
      available techniques, nanoparticle tracking analysis (NTA) can measure individual
      particles to create a size distribution and measure the particle number.
      Therefore, we explore the possibility to use these data to calculate the particle
      mass distribution. Additionally, we further developed the NTA methodology to
      explore its suitability for analysis of ENM in complex matrices by measuring ENM
      agglomeration and sedimentation in municipal solid waste incineration landfill
      leachates over time. 100 nm Au ENM were spiked into DI H2O and synthetic and
      natural leachates. We present the possibility of measuring ENM in the presence of
      natural particles based on differences in particle refractivity indices,
      delineate the necessity of creating a calibration curve to adjust the given NTA
      particle number concentration, and determine the instruments linear range under
      different conditions. By measuring the particle size and the particle number
      distribution, we were able to calculate the ENM mass remaining in suspension. By
      combining these metrics together with transmission electron microscopy (TEM)
      analyses, we could assess the extent of both homo- and heteroagglomeration as
      well as particle sedimentation. Reporting both size and mass based metrics is
      common in atmospheric particle measurements, but now, the NTA can give us the
      possibility of applying the same approach also to aqueous samples.

PMID- 28438021
TI  - A New Improved and Extended Version of the Multicell Bacterial Simulator gro.
AB  - gro is a cell programming language developed in Klavins Lab for simulating colony
      growth and cell-cell communication. It is used as a synthetic biology prototyping
      tool for simulating multicellular biocircuits and microbial consortia. In this
      work, we present several extensions made to gro that improve the performance of
      the simulator, make it easier to use, and provide new functionalities. The new
      version of gro is between 1 and 2 orders of magnitude faster than the original
      version. It is able to grow microbial colonies with up to 105 cells in less than
      10 min. A new library, CellEngine, accelerates the resolution of spatial physical
      interactions between growing and dividing cells by implementing a new shoving
      algorithm. A genetic library, CellPro, based on Probabilistic Timed Automata,
      simulates gene expression dynamics using simplified and easy to compute digital
      proteins. We also propose a more convenient language specification layer,
      ProSpec, based on the idea that proteins drive cell behavior. CellNutrient,
      another library, implements Monod-based growth and nutrient uptake
      functionalities. The intercellular signaling management was improved and extended
      in a library called CellSignals. Finally, bacterial conjugation, another local
      cell-cell communication process, was added to the simulator. To show the
      versatility and potential outreach of this version of gro, we provide studies and
      novel examples ranging from synthetic biology to evolutionary microbiology. We
      believe that the upgrades implemented for gro have made it into a powerful and
      fast prototyping tool capable of simulating a large variety of systems and
      synthetic biology designs.

PMID- 28438023
TI  - Proteomic Analysis of the Effect of DHA-Phospholipids from Large Yellow Croaker
      Roe on Hyperlipidemic Mice.
AB  - Previously, we found that phospholipids derived from large yellow croaker
      (Pseudosciaena crocea) roe had a higher level of docosahexaenoic acid (DHA-PL),
      which had beneficial effects on lipid metabolism. However, the mechanism by which
      DHA-PL from P. crocea roe exerts these effects has not yet been illuminated.
      Herein, we investigated the underlying molecular action of DHA-PL by examining
      changes in liver protein expression in control, hyperlipidemic, and DHA-PL
      treated mice. A total of 16 proteins, 9 up-regulated and 7 down-regulated, were
      identified and classified into several metabolic pathways, such as fat digestion
      and absorption, peroxisome proliferator activated receptor (PPAR) signaling, and
      antigen processing and presentation; the largest functional class found was that
      of fat digestion and absorption. We revealed Apoa1 to be a biomarker of DHA-PL
      effects on hyperlipidemic mice by DHA-PL diet. These results not only improve our
      current understanding of hyperlipidemic regulation by DHA-PL, but also suggest
      that DHA-PL should be applied as a beneficial food additive.

PMID- 28438025
TI  - Fusion of polymeric material-binding peptide to cell-adhesion artificial proteins
      enhances their biological function.
AB  - Orientation-controlled protein immobilization on a solid substrate surface is
      important for the development of biomedical materials such as scaffolds used in
      tissue engineering. In this study, the authors demonstrated that the introduction
      of material-binding peptides (MBPs) in Arg-Gly-Asp (RGD)-fused artificial
      proteins called blocking peptide fragment (BPF), which are fragments (residues
      419-607) of the molecular chaperone DnaK, enhances the oriented adsorption of
      proteins on the polymer surface and improves their cell adhesion capability. The
      authors used isotactic poly(methyl methacrylate) (it-PMMA) binding peptides (c02
      peptide; ELWRPTR) as a model system. A quartz crystal microbalance study showed
      that the fusion of c02 peptide with BPF-RGD proteins slightly enhanced adsorption
      on it-PMMA surfaces. On the other hand, atomic force microscopic images of it
      PMMA surfaces adsorbed with c02-BPF-RGD proteins showed a dotlike pattern, with
      the sizes of the dots comparable to those of BPF protein dimers, indicating that
      the immobilization of c02-BPF-RGD partially occurred in an oriented manner via
      specific interaction between the c02 peptide and it-PMMA. This is in sharp
      contrast to the random adsorption of BPF-RGD and BPF. These results were
      supported by results of the enzyme-linked immunosorbent assay using an
      antihistidine tag antibody. In addition, c02-BPF-RGD adsorbed on it-PMMA showed
      better cell attachment and spreading ability than BPF-RGD and BPF. This
      methodology can be applied to other MBP systems and cell-binding motifs. Thus,
      BPF-based artificial cell adhesion proteins fused with MBPs might be useful as
      surface modifiers of polymer materials for improving their cell adhesion ability.

PMID- 28438024
TI  - Biomedical surface analysis: Evolution and future directions (Review).
AB  - This review describes some of the major advances made in biomedical surface
      analysis over the past 30-40 years. Starting from a single technique analysis of
      homogeneous surfaces, it has been developed into a complementary, multitechnique
      approach for obtaining detailed, comprehensive information about a wide range of
      surfaces and interfaces of interest to the biomedical community. Significant
      advances have been made in each surface analysis technique, as well as how the
      techniques are combined to provide detailed information about biological surfaces
      and interfaces. The driving force for these advances has been that the surface of
      a biomaterial is the interface between the biological environment and the
      biomaterial, and so, the state-of-the-art in instrumentation, experimental
      protocols, and data analysis methods need to be developed so that the detailed
      surface structure and composition of biomedical devices can be determined and
      related to their biological performance. Examples of these advances, as well as
      areas for future developments, are described for immobilized proteins, complex
      biomedical surfaces, nanoparticles, and 2D/3D imaging of biological materials.

PMID- 28438026
TI  - Intramuscular Lorazepam for Status Epilepticus in Children With Complex Medical
      and Physical Disabilities.
AB  - BACKGROUND: A protocol was developed to achieve status epilepticus (SE)
      resolution: step 1, intramuscular (IM) lorazepam; step 2, repeat IM lorazepam;
      step 3, rectal diazepam. OBJECTIVE: The primary objective was to identify the
      number of patients with SE resolution after step 1. Secondary objectives included
      categorization of mean number of IM doses per episode and patient factors
      associated with SE resolution. METHODS: This was a retrospective study of
      patients <21 years old with complex medical and physical disabilities admitted
      over 5 years. For analysis, IM dosing was categorized as high dose (>0.05
      mg/kg/dose) and low dose (<=0.05 mg/kg/dose). A generalized linear mixed-model
      regression was used to assess the relationship with SE resolution at step 1 and
      patient characteristics. RESULTS: A total of 44 patients were included (n = 162
      episodes). SE resolution was noted in 68.5% of episodes after step 1. Models were
      stratified by gender to present odds of SE resolution at step 1 versus step 2/3.
      For women, no covariate was significant. For men, the odds of SE resolution at
      step 1 were 14.9 times higher in those receiving 2 versus 4 maintenance
      antiepileptics, adjusting for covariates. Additionally, odds of resolution at
      step 1 was 3.1 times higher for high-dose versus low-dose lorazepam in males,
      adjusting for covariates, but was not statistically significant. CONCLUSIONS: SE
      resolution was noted in 68.5% after step 1. Unadjusted, females had a higher odds
      of SE resolution at step 1 than males. In males, high-dose lorazepam had higher
      odds of SE resolution at step 1 than low-dose lorazepam, though not significantly
      different.

PMID- 28438027
TI  - Attitudes towards homosexuals in seven Caribbean countries: implications for an
      effective HIV response.
AB  - Between 2000 and 2015, the number of people newly infected with HIV in the
      Caribbean decreased by 76% and HIV-related deaths by 42%. The number of people
      living with HIV (PLHIV) on anti-retroviral therapy (ART) increased from near zero
      to 50% (44% to 57%) in 2015. In many Caribbean countries communities of men-who
      have-sex-with-other-men (MSM) have higher incidence and prevalence of HIV. They
      are often stigmatized and subjected to both social and institutional
      discrimination. This study compared attitudes of the general public obtained
      through public opinion polls 2013-2014 towards homosexuals and willingness to
      socialize with them in seven Caribbean countries. Informants were asked if they
      "hate, tolerate or accept" homosexuals and if they would socialize with them. In
      St. Vincent 53% indicated they "hate" homosexuals, compared with 12% in Suriname;
      the converse was observed for those who "accept" homosexuals; 63% of St. Vincent
      informants would not socialize with homosexuals, compared with 25% in Suriname.
      Findings for the other 5 countries fell within these ranges. Women were more
      likely to accept and socialize with homosexuals, as were informants with a
      tertiary education and "passive" religious believers. These groups are less
      likely to adhere to a culture of "compulsory heterosexuality" or "hyper
      masculinity" dominant among Caribbean men. The homophobic views expressed by
      these cultures result in stigma and discrimination by members of the "general"
      public towards MSM. This negatively affects the involvement of MSM in successful
      national HIV responses. Public messaging, communications campaigns and
      educational measures need to be employed to change the culture of "compulsory
      heterosexuality" or "hyper-masculinity" that result in stigma and discrimination
      of homosexuals to improve early access to services by MSM. Repeat use of well
      performed opinion polls is one method that can be employed to monitor progress
      over time in "key" and "general" populations.

PMID- 28438028
TI  - Cardiac rehabilitation programme as a non-pharmacological platelet inhibitory
      tool in acute coronary syndrome survivors.
AB  - Background Acute coronary syndrome is associated with platelet hyperactivity,
      which in its persistent form, promotes recurrent thrombotic events. Complex
      cardiac rehabilitation after acute coronary syndrome improves clinical outcome;
      however, its effect on platelet hyperactivity is unknown. Design and methods We
      enrolled 84 acute coronary syndrome patients on dual antiplatelet therapy, who
      underwent a new complex cardiac rehabilitation programme (NovaCord physiotherapy,
      lifestyle counselling, strict diet, stress management and regular coaching) and
      51 control acute coronary syndrome patients with traditional cardiac
      rehabilitation. Platelet functionality was determined at enrolment and at three
      months follow-up by aggregometry, serum platelet-derived growth factor levels,
      total- and platelet-derived microvesicle counts (PMV; CD41a+/CD61+, CD62P+).
      Results Platelet aggregation parameters and platelet-derived growth factor levels
      were significantly decreased in the complex cardiac rehabilitation group at three
      months (1 ug/ml collagen, median (interquartile range): 22 (10-45) vs 14 (7.5
      25.5)%, p = 0.0015; 2 ug/ml collagen: 36 (22-60) vs 26.5 (16-37)%, p = 0.0019;
      1.25 uM adenosine-diphosphate: 4.5 (1-10) vs 1 (0-3)%, p = 0.0006; 5 uM adenosine
      diphosphate: 27 (16-38) vs 22 (12-31)%, p = 0.0078; epinephrine: 33 (15-57) vs 27
      (12-43)%, p = 0.01; platelet-derived growth factor: 434.6 (256.0-622.7) vs 224.8
      (148.5-374.1) pg/ml, p = 0.0001). In contrast, these changes were absent or did
      not reach statistical significance in the traditional cardiac rehabilitation
      group. Platelet-derived microvesicle counts were significantly decreased in both
      groups, while total microvesicle count was significantly reduced only in the
      complex cardiac rehabilitation group (median (interquartile range): 3945.5 (2138
      5661) vs 1739 (780-2303) count/ul; p = 0.0001). Conclusions Platelet
      hyperactivity three months after acute coronary syndrome significantly decreased
      in patients undergoing complex cardiac rehabilitation. Besides dual antiplatelet
      therapy, effective management and comprehensive control of cardiovascular risk
      factors might represent a new, non-pharmacological approach to influence platelet
      functionality.

PMID- 28438029
TI  - Posterior Tibialis Tendon Rupture in a Closed Bimalleolar-Equivalent Ankle
      Fracture: Case Report.
AB  - : Ankle fractures with an associated posterior tibialis tendon (PTT) rupture are
      rare injuries and have only been described in a number of case reports. These
      prior reports include patients that had an open fracture and/or an associated
      medial malleolar fracture component. In this unique case report, we present a
      patient that sustained a closed bimalleolar-equivalent ankle fracture/dislocation
      without medial malleolar involvement which was irreducible due to a PTT rupture
      and subsequent distal segment interposition in the tibiotalar joint.
      Identification of acute PTT rupture with associated ankle fracture is important
      because early repair is associated with significantly better functional outcomes
      compared with late repair. These injury patterns may easily be missed due to the
      limitations with physical examination and standard imaging often encountered
      during initial evaluation of routine ankle fractures. Therefore, physicians
      should maintain a high level of suspicion in the appropriate clinical setting in
      order to provide appropriate diagnosis and timely surgical intervention. LEVELS
      OF EVIDENCE: Descriptive, Level V: Single case report.

PMID- 28438030
TI  - Non-specialist psychosocial support interventions for women living with HIV: A
      systematic review.
AB  - Many women living with HIV experience a range of physical, social, and
      psychological challenges linked to their HIV status. Psychosocial support
      interventions may help women cope with these challenges and may allow women to
      make better decisions around their sexual and reproductive health (SRH), yet no
      reviews have summarized the evidence for the impact of such interventions on well
      being and SRH decision-making among women living with HIV. We systematically
      reviewed the evidence for non-specialist delivered psychosocial support
      interventions for women living with HIV, which are particularly relevant in low
      resource settings. Outcomes of interest included mental, emotional, social well
      being and/or quality of life, common mental health disorders, and SRH decision
      making. Searching was conducted through four electronic databases and secondary
      reference screening. Systematic methods were used for screening and data
      abstraction. Nine articles met the inclusion criteria, showing positive or mixed
      results for well-being and depressive symptoms indicators. No studies reported on
      SRH decision-making outcomes. The available evidence suggests that psychosocial
      support interventions may improve self-esteem, coping and social support, and
      reduce depression, stress, and perceived stigma. However, evidence is mixed. Most
      studies placed greater emphasis on instrumental health outcomes to prevent HIV
      transmission than on the intrinsic well-being and SRH of women living with HIV.
      Many interventions included women living with HIV in their design and
      implementation. More research is required to understand the most effective
      interventions, and their effect on sexual and reproductive health and rights.

PMID- 28438031
TI  - MRI-based finite element modeling of facial mimics: a case study on the paired
      zygomaticus major muscles.
AB  - Finite element simulation of facial mimics provides objective indicators about
      soft tissue functions for improving diagnosis, treatment and follow-up of facial
      disorders. There is a lack of in vivo experimental data for model development and
      validation. In this study, the contribution of the paired Zygomaticus Major (ZM)
      muscle contraction on the facial mimics was investigated using in vivo
      experimental data derived from MRI. Maximal relative differences of 7.7% and 37%
      were noted between MRI-based measurements and numerical outcomes for ZM and skin
      deformation behaviors respectively. This study opens a new direction to simulate
      facial mimics with in vivo data.

PMID- 28438032
TI  - Influence of drying methods on chemical compositions, antioxidant and
      antibacterial activity of essential oil from lemon peel.
AB  - The influence of natural, hot-air and infrared drying on chemical composition and
      bioactivity of lemon peel essential oil are investigated in this study. The
      results showed that drying resulted in losses or increases of some components or
      production of some new substances, but the d-limonene (59.52-70.01%) was found as
      the main component of essential oil. Drying brought about decreases in the yield,
      antioxidant and antibacterial activity of essential oil. However, the natural
      drying had little effect, while the hot-air and infrared drying resulted in
      significant decreases in these parameters, especially at the higher temperature.
      The yield was the lowest under hot-air drying (60  degrees C) and decreased by
      78%, while infrared drying (60  degrees C) sample exhibited the lowest
      antioxidant and antibacterial activities. Infrared drying was easier to lead to
      the decrease in bioactivity than hot-air drying at the same temperature. These
      results provided the theoretical basis for drying lemon peel.

PMID- 28438033
TI  - Effects of polyphenol removal methods on the in vitro exsheathment inhibitory
      activity of Lysiloma latisiliquum extracts against Haemonchus contortus larvae.
AB  - It has been suggested that the anthelmintic (AH) activity of tannin-rich forages
      is related to their tannin content. However, reports on tropical fodders such as
      Lysiloma latisiliquum describe the same AH activity after the addition of tannin
      blocking agents, suggesting that the activity either depends on the method of
      tannin blocking/removal or is due to other type of secondary metabolites. This
      study compared both the effect of the drying process of the plant material and
      the effect of different polyphenol removal methods on the AH activity of L.
      latisiliquum acetone-water extracts when tested against Haemonchus contortus. The
      results showed that the extraction of oven-dried (OD) leaves of L. latisiliquum
      yielded a CT-free extract with high AH activity. However, polyphenol-free
      fractions showed similar or lower AH activity levels as of those original OD
      extract. HPLC analysis confirmed that common polyphenolic metabolites are not
      responsible for the AH activity of L. latisiliquum.

PMID- 28438034
TI  - Changes in physical activity following total hip or knee arthroplasty: a matched
      case-control study from the EPIC-Norfolk cohort.
AB  - OBJECTIVE: To assess self-reported physical activity changes pre- compared to
      post-operatively in patients undergoing total hip or knee arthroplasty, and to
      compare this to an age- and gender-matched cohort of people who have not
      undergone arthroplasty. DESIGN: Population-based prospective cohort study.
      SETTING: Norfolk, United Kingdom. SUBJECTS: People who had undergone hip or knee
      arthroplasty, compared to an age- and gender-matched non-arthroplasty cohort.
      INTERVENTION: Primary total hip or knee arthroplasty. MAIN MEASURES: Physical
      activity, measured using the EPIC Physical Activity Questionnaire (EPAQ2).
      RESULTS: A total of 400 people from the EPIC-Norfolk community cohort were
      identified who had undergone hip or knee arthroplasty. In all, 767 people were
      identified to form an age- and gender-matched non-arthroplasty cohort. Mean post
      operative follow-up was 43 months post-total hip and 41 months post-total knee
      arthroplasty. There was a statistically significant reduction from pre- to post
      arthroplasty in the number of flights of stairs climbed weekly (hip: mean
      difference (MD): 6.8; P < 0.01; knee: MD: 10.2; P < 0.01), duration of walking
      (hip: MD: 1.4 hours/week; P = .02; knee: MD: 2.2 hours/week; P < 0.01) and
      duration of total recreational activity (hip: MD: 1.1 hours/week; P = 0.02).
      Compared to the non-arthroplasty cohort, duration of physical activity was lower
      post-total hip arthroplasty (MD: 1.8 hours/week; P = 0.01). The number of flights
      of stairs climbed weekly (MD: 12.0; P < 0.01), total recreational activity (MD:
      1.7 hours/week; P = 0.04) and physical activity energy expenditure (MD: 5.7 Mets
      hours/week; P = 0.05) were lower for people post-total knee arthroplasty compared
      to the matched controls. CONCLUSIONS: Physical activity did not increase, and in
      some instances decreased, following total hip or knee arthroplasty.

PMID- 28438035
TI  - Dual Burden of Malnutrition Among Adolescents of Smallholder Coffee Farming
      Households of Jimma Zone, Southwest Ethiopia.
AB  - BACKGROUND: Substantial evidence is emerging on the coexistence of double burden
      of malnutrition on adolescents of low-income countries, shaping the health
      challenges of the upcoming adult generation for the worst. Whether nutritional
      status markers of adolescents in the cash crop setting are on par with economic
      gains remains uncertain. Thus, we investigated the nutritional outcomes of
      adolescents and their determinants in coffee farming households. METHODS: The
      survey was carried out in 3 top coffee-producing districts of Jimma Zone,
      Ethiopia. Five hundred fifty mothers/caregivers and their respective adolescents
      were selected using multistage random sampling. Anthropometric data were
      converted into height-for-age and body-mass-index-for-age Z scores using WHO
      Anthroplus software and analyzed by SPSS for windows. RESULTS: Prevalence of
      thinness, stunting, and overweight/obesity were 11.6%, 15.6%, and 7.1%,
      respectively. The odds of stunting among adolescents in households in the lowest
      wealth tertile was nearly 6-fold higher compared to the highest tertile (adjusted
      odds ratio [AOR] = 5.6 [2.6-12]). Conversely, the odds of overweight/obesity was
      higher among adolescents in the households in the middle wealth tertile (AOR =
      2.72 [1.08-6.86]) compared to the highest tertile. Adolescents living in
      households with low-dependent age-groups were more than twice likely to be
      overweight/obese (AOR = 2.58 [1.06-6.24]). CONCLUSION: The current study revealed
      the presence of substantial dual burden of malnutrition. In such a setting, it is
      critical to draw a fine line and trade-off for eliminating morbidity and
      mortality of undernutrition, without triggering the risk of overweight/obesity.

PMID- 28438036
TI  - Enhancing Periconceptional Health by Targeting Postpartum Mothers at Rural WIC
      Clinics.
AB  - The overall goal of this pilot quality improvement (QI) intervention was to (1)
      assess the feasibility of making a WIC (Women, Infants, and Children) systems
      level change that added measurement of maternal weight and discussion of maternal
      health habits into each postpartum maternal and offspring visit in rural clinics
      in Colorado and (2) assess the impacts of the intervention on maternal diet,
      physical activity, and weight status. A mixed-method evaluation approach was used
      involving the collection of quantitative data (HeartSmartMoms usage reports,
      manual WIC chart reviews [to calculate screening rates], pre-/postsurveys, and
      weight status [body mass index]) and qualitative data (focus groups and project
      team meeting minutes). It was determined it is feasible to make a short-term
      systems-level change; however, many barriers were encountered in doing so, and
      the results were not sustained. The QI intervention did decrease participants'
      daily consumption of sugar-sweetened beverages and maternal weight status
      (controlling for maternal age and language), but did not improve any other
      eating/physical activity behaviors. Lessons learned and recommendations to
      improve the implementation of health promotion interventions aimed at improving
      postpartum maternal health, which can increase health during the periconceptional
      phase, and in turn, improve the health outcomes for a child, are discussed.

PMID- 28438037
TI  - Evaluation of Tobacco Control Policies in San Francisco Homeless Housing
      Programs.
AB  - BACKGROUND: The 2014 Surgeon General's Report noted that high smoking rates in
      vulnerable populations such as the homeless have been a persistent public health
      problem; smoking prevalence among individuals experiencing homelessness exceeds
      70%. Historically, service providers for the homeless have not enacted
      comprehensive tobacco control policies. METHOD: We conducted a qualitative study
      of homeless housing programs in San Francisco. Administrators representing 9 of
      the city's 11 homeless service agencies were interviewed to assess institutional
      smoking-related policies and cessation programs and perceived barriers and
      receptivity to instituting tobacco control interventions. RESULTS: Respondents
      indicated that although most programs had adopted smoke-free grounds and some had
      eliminated evidence of staff smoking, the smoking status of clients was assessed
      only when required by funders. None of the programs offered smoking cessation
      interventions. Most administrators were receptive to adopting policies that would
      promote a tobacco-free culture; however, they noted that their clients had unique
      challenges that made traditional smoking cessation programs unfeasible.
      CONCLUSIONS: Homeless housing programs in San Francisco have not yet adopted a
      tobacco-free culture. Existing policies were created in response to external
      mandates, and smoking cessation programs may need to be modified in order to
      effectively reach clients.

PMID- 28438038
TI  - Bisamides and rhamnosides from mangrove actinomycete Streptomyces sp. SZ-A15.
AB  - Four new bisamides 1-4, and two new rhamnosides (5, 6), along with four known
      compounds 7-10, were isolated from a scale culture of the mangrove-derived
      actinomycete Streptomyces sp. SZ-A15. All structures were determined through
      analysis of the UV, IR, HRESIMS, 1D and 2D NMR spectra as well as by comparison
      with literature data. BRD4 inhibition of all isolated compounds was evaluated. As
      for the ability to inhibit protein BRD4, compound 9 exhibited moderate activity
      with the value of 78.4 +/- 2.2% at 10 MUM.

PMID- 28438039
TI  - Anti-complementary constituents of Anchusa italica.
AB  - Activity-guided fractionation for complement inhibitors led to the isolation of
      24 known compounds from Anchusa italica. Chemical types include eight
      megastigmane compounds, five triterpenoid compounds, five lignan compounds, three
      flavonoid compounds, two alkaloid compounds and one phenthyl alcohol compound.
      Among which, a lignan (medioresinol), an alkaloid (5-hydroxypyrrolidin-2-one) and
      a flavonoid (5-hydroxyl-3', 4', 6, 7-tetramethoxy flavone) exhibited better
      anticomplementary effects with CH50 values ranging from 0.07 to 0.82 mM, which
      are plausible candidates for developing potent anticomplementary agents.

PMID- 28438040
TI  - Semi-preparative HPLC purification of delta-tocotrienol (delta-T3) from Elaeis
      guineensis Jacq. and Bixa orellana L. and evaluation of its in vitro anticancer
      activity in human A375 melanoma cells.
AB  - In this work, we report a rapid and convenient HPLC-UV-DAD method for the
      isolation of delta-T3 on semi-preparative scale from two different vitamin E rich
      processed, commercially available products obtained from the fruits of Elaeis
      guineensis Jacq. (oil palm) and from the seeds of Bixa orellana L. (achiote
      tree). Chromatography was run using reverse phase (RP) C-18 columns and HPLC
      grade acetonitrile as mobile phase. The purity of the isolated delta-T3, assessed
      by GC-MS and 1H NMR was above 98%. The delta-T3 cytotoxic activity found in vitro
      against the proliferation of human A375 melanoma cells compared to that of the
      other delta-T3 free tocols mixture suggest its primary role in the experimental
      anticancer activity observed for palm oil derived products. Taken altogether, the
      results of this study highlight the importance of the application of suitable
      purification systems for the preparations of tocotrienols prior to their
      experimental or clinical testing.

PMID- 28438041
TI  - Design of multifunctional liposome-quantum dot hybrid nanocarriers and their
      biomedical application.
AB  - Luminescent semiconductor nanocrystals, also known as quantum dots (QDs), have
      rich surface chemistry and unique optical properties that make them useful as
      probes or carriers for molecular diagnostics and therapeutics. However, their
      potential toxicity and instability in biological environments have puzzled
      scientific researchers. Much research effort has been devoted to encapsulation of
      QDs with liposomal hybrids to make them versatile nanocarriers for simultaneous
      therapeutics and diagnostics (theranostics) and considerable progress has been
      made over recent years. We provide an overview of the use of QD-liposome
      complexes (QLCs) for imaging applications, in particular applications in
      theranostics. More specifically, the design considerations, intracellular uptake
      and tissue-specific targeting of QLCs are highlighted. Current findings of QLCs
      for theranostics are discussed. We also discuss the challenges and highlight
      future directions for applications of liposome-QD hybrid nanocarriers in the
      biomedical arena.

PMID- 28438042
TI  - Ethnic differences in the cardiac responses to aerobic exercise.
AB  - BACKGROUND: Cardiovascular disease disproportionately affects North American
      Indigenous populations. Ethnic differences in cardiac responses to exercise are
      known, though Indigenous populations response is unknown. To evaluate cardiac
      responses to aerobic exercise among Canadian Indigenous and European adults.
      METHODS: Indigenous (N = 12, 4 females, 1 male incomplete) and European (N = 12,
      all completed) Canadian age and sex-matched adults 19-40 years and free of
      cardiovascular disease or diabetes completed a cycle ergometer maximal aerobic
      power test and 30 min at 60% maximal aerobic capacity on two separate days.
      Echocardiographic assessments preceded and immediately followed exercise.
      RESULTS: Responses to maximal exercise were similar among ethnicities including
      decreases in stroke volume index, cardiac output index and ejection fraction, and
      increases in arterial-ventricular coupling. However, following submaximal
      exercise, only Indigenous adults demonstrated reductions in end systolic volume,
      end diastolic volume (154.8 +/- 40.6 mL to 136.5 +/- 33.0 mL, p = 0.01, vs. 149.4
      +/- 22.4 mL to 147.1 +/- 27.0 mL; p = 0.81), stroke volume index (44.9 +/- 8.7 mL
      m-2 to 38.0 +/- 6.5 mL m-2, p = 0.002, vs. 46.4 +/- 7.1 mL m-2 to 44.0 +/- 6.5 mL
      m-2; p = 0.28) and arterial compliance. CONCLUSION: Indigenous and European
      adults demonstrated similar cardiac responses to maximal exercise, though only
      Indigenous adults demonstrated cardiac responses to submaximal exercise.

PMID- 28438043
TI  - Comparative Effectiveness and Safety Analysis of Dual Antiplatelet Therapies
      Within an Integrated Delivery System.
AB  - BACKGROUND: Dual antiplatelet therapy is a mainstay of care for percutaneous
      coronary intervention (PCI) patients; however, uncertainty exists in real-world
      practice about comparative effectiveness and safety outcomes. OBJECTIVE: To
      evaluate outcomes of different oral P2Y12 inhibitors in PCI patients. METHODS: We
      retrospectively studied patients treated between July 1, 2010, and December 31,
      2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1
      antiplatelet (switch) during PCI. Outcomes were evaluated for major adverse
      cardiovascular events (MACE) and bleeding at 1 year. Propensity score matching
      with Cox proportional hazards analysis was used to determine predictors of MACE
      and bleeding. RESULTS: A total of 8127 patients were included: clopidogrel (n =
      6872), prasugrel (n = 605), ticagrelor (n = 181), and switch (n = 469). Treatment
      with prasugrel was associated with the lowest risk of MACE using multivariate
      regression (odds ratio [OR] = 0.57; 95% CI = 0.36-0.92; P = 0.02). In the
      propensity score-matched analysis, only the prasugrel group was associated with a
      lower risk of MACE compared with the clopidogrel group. Clopidogrel was
      associated with the lowest risk of major bleeding using multivariate regression
      (OR = 0.64; 95% CI = 0.42-0.98; P = 0.042). Both ticagrelor (hazard ratio [HR] =
      2.00; 95% CI = 1.11-3.59) and the switch groups (HR = 1.65; 95% CI = 1.09-2.50)
      were associated with a greater risk of major bleeding compared with clopidogrel.
      However, no differences were found in the propensity score-matched analysis.
      CONCLUSIONS: Dual antiplatelet therapies differed in both MACE and bleeds in a
      real-world setting of PCI. Prasugrel was associated with fewer MACE, whereas
      clopidogrel had fewer major bleeding events.

PMID- 28438044
TI  - Hepatic encephalopathy.

PMID- 28438045
TI  - Calculation of reference change values using more than two results is a difficult
      task.

PMID- 28438046
TI  - Calculation of reference change values using more than two results is a difficult
      task: a response.

PMID- 28438047
TI  - Epidemiology of acute kidney injury in critically ill children and young adults.

PMID- 28438048
TI  - The Impact of Infant Well-Child Care Compliance and Social Risks on Emergency
      Department Utilization.
AB  - Deployment of medical and social services at well-child visits promotes child
      health. A retrospective review of the electronic health record was conducted for
      infants presenting for their "newborn" visit over a 2-year period at an urban,
      academic primary care center. Primary outcomes were time to first emergency
      department (ED) visit, number of ED visits (emergent or nonemergent), and number
      of nonemergent ED visits by 2 years of life. Records from 212 consecutive
      newborns were evaluated-59.9% were black/African American and 84.4% publicly
      insured. A total of 72.6% visited the ED by 2 years of life. Sixty percent
      received >=5 well-child visits by 14 months; 25.9% reported >=1 social risk.
      There were no statistically significant associations between number of completed
      well-child visits, or reported social risks, and ED utilization. Renewed focus on
      preventive care delivery and content and its effect on ED utilization, and other
      patient outcomes, is warranted.

PMID- 28438049
TI  - Ocular non-P450 oxidative, reductive, hydrolytic, and conjugative drug
      metabolizing enzymes.
AB  - Metabolism in the eye for any species, laboratory animals or human, is gaining
      rapid interest as pharmaceutical scientists aim to treat a wide range of so
      called incurable ocular diseases. Over a period of decades, reports of metabolic
      activity toward various drugs and biochemical markers have emerged in select
      ocular tissues of animals and humans. Ocular cytochrome P450 (P450) enzymes and
      transporters have been recently reviewed. However, there is a dearth of collated
      information on non-P450 drug metabolizing enzymes in eyes of various preclinical
      species and humans in health and disease. In an effort to complement ocular P450s
      and transporters, which have been well reviewed in the literature, this review is
      aimed at presenting collective information on non-P450 oxidative, hydrolytic, and
      conjugative ocular drug metabolizing enzymes. Herein, we also present a list of
      xenobiotics or drugs that have been reported to be metabolized in the eye.

PMID- 28438050
TI  - Exploring Proxy Measures of Mutuality for Strategic Partnership Development: A
      Case Study.
AB  - Partnerships between academic and clinical-based health organizations are
      becoming increasingly important in improving health outcomes. Mutuality is
      recognized as a vital component of these partnerships. If partnerships are to
      achieve mutuality, there is a need to define what it means to partnering
      organizations. Few studies have described the elements contributing to mutuality,
      particularly in new relationships between academic and clinical partners. This
      study seeks to identify how mutuality is expressed and to explore potential proxy
      measures of mutuality for an alliance consisting of a hospital system and a
      School of Public Health. Key informant interviews were conducted with faculty and
      hospital representatives serving on the partnership steering committee. Key
      informants were asked about perceived events that led to the development of the
      Alliance; perceived goals, expectations, and outcomes; and current/future roles
      with the Alliance. Four proxy measures of mutuality for an academic-clinical
      partnership were identified: policy directives, community beneficence,
      procurement of human capital, and partnership longevity. Findings can inform the
      development of tools for assisting in strengthening relationships and ensuring
      stakeholders' interests align with the mission and goal of the partnership by
      operationalizing elements necessary to evaluate the progress of the partnership.

PMID- 28438052
TI  - Successful treatment of NO-induced methemoglobinemia with low-dose vitamin C.

PMID- 28438051
TI  - Similarity of female central (hypogonadotropic) hypogonadism and postmenopause.
AB  - OBJECTIVES: Central (hypogonadotropic) hypogonadism in women could be a cause of
      persistent amenorrhea and hypoestrogenemia as observed in postmenopause. This
      study aimed to compare the clinical, hormonal and biochemical features in women
      with non-physiological (central hypogonadism) and physiological (postmenopause)
      hypoestrogenemia. METHODS: A total of 161 young women, median age 24.9 years
      (interquartile range (IQR) 21.2; 30.5) with central hypogonadism (with isolated
      hypogonadotropic hypogonadism, n = 76, and with hypopituitarism, n = 85), 53
      healthy young women, median age 23.9 years (IQR 23.1; 28.0) and 50 healthy
      postmenopausal women, median age 56.0 years (IQR 53.1; 58.5), were examined.
      Psychoemotional, neurovegetative and urogenital symptoms, sex steroid levels,
      parameters of lipid and mineral metabolism were evaluated. RESULTS: In young
      women with central hypogonadism, the frequencies of psychoemotional,
      neurovegetative and urogenital complaints differed significantly from those in
      healthy young women and were similar to those in postmenopausal women.
      Concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate,
      parameters of lipid and mineral metabolism as well as quality of life in women
      with central hypogonadism were not typical of healthy young women but were
      similar to those of postmenopausal women of middle/old age. CONCLUSIONS: Despite
      the young age of women with central hypogonadism, clinical, hormonal and
      biochemical abnormalities were similar in many aspects to those in postmenopausal
      women at middle/old age. These revealed features could be considered as signs of
      premature aging in young amenorrheic women with low gonadotropin levels.

PMID- 28438053
TI  - Scorpion Venom Causes Upregulation of p53 and Downregulation of Bcl-xL and BID
      Protein Expression by Modulating Signaling Proteins Erk1/2 and STAT3, and DNA
      Damage in Breast and Colorectal Cancer Cell Lines.
AB  - Scorpion venoms efficiently block the normal neurotransmitter signaling pathway
      by prejudicing the ion channel operating mechanism in the body system. Besides
      its negative effect, venoms also possess some beneficial qualities for humans.
      They have also been shown to exhibit anticancer properties in various cancer
      types. This unique property of the venom as an anticancer agent is mainly a
      result of its role in initiating apoptosis and inhibiting several signaling
      cascade mechanisms that promote cancer cell proliferation and growth. In this
      study, we examine the effect of venom on phenotypic changes as well as changes at
      the molecular levels in colorectal and breast cancer cell lines. A dramatic
      decrease in cell invasion was observed in both cancer cell lines on venom
      treatment. Additionally, there was decrease in IL-6, RhoC, Erk1/2, and STAT3 in
      venom-treated cell lines, providing strong evidence of its anticancer properties.
      Furthermore, decrease in the expression of antiapoptotic proteins and also
      upregulation of proapoptotic ones by these lines were observed on venom
      treatment. Moreover, a vivid picture of DNA damage was also detected on venom
      treatment. In conclusion, scorpion venom possesses significant potential as an
      anticancer agent against colorectal and breast cancer cell lines.

PMID- 28438054
TI  - Evaluation of Active Hexose Correlated Compound (AHCC) in Combination With
      Anticancer Hormones in Orthotopic Breast Cancer Models.
AB  - OBJECTIVE: To determine the impact on antitumor activity when active hexose
      correlated compound (AHCC) in combination with anticancer hormonal agents in
      orthotopic mouse models of human estrogen receptor positive breast cancer and
      evaluate impact of AHCC on aromatase activity. METHODS: The study consisted of 7
      treatment arms (n=10) conducted in 2 breast cancer mouse models: MCF-7 and ZR-75.
      Treatment groups included untreated, vehicle, AHCC 50 mg/kg, AHCC 50 mg/kg +
      tamoxifen 10 mg/kg, tamoxifen 10 mg/kg, AHCC 50 mg/kg + letrozole 10 ug/mouse, or
      letrozole 10 ug/mouse. All treatments were administered daily by oral gavage for
      12 weeks. Tumors were measured 3 times a week. In vitro estrone and 17beta
      estradiol enzyme immunoassay was used to evaluate aromatase activity. RESULTS:
      There was no difference in the activity with the combination of AHCC + tamoxifen
      compared with tamoxifen ( P = 0.29). In the ZR-75 model (catechol- O
      methyltransferase [COMT] wild-type), there was no difference in activity with the
      letrozole + AHCC compared with letrozole. However, in the MCF-7 model (COMT
      variant), AHCC + letrozole resulted in a decrease in activity compared with
      letrozole ( P < 0.01). Immunoassay data suggested that AHCC is a potential
      inducer of aromatase activity. In both tumor models, there was cytotoxicity
      observed with AHCC compared with untreated ( P < 0.02). CONCLUSION: AHCC did not
      change the activity of tamoxifen. AHCC may have some interaction with letrozole
      in patients with COMT variant genotype. AHCC had cytotoxicity that warrents
      additional studies to evaluate its potential role for consolidation/prevention of
      breast cancer.

PMID- 28438055
TI  - Text and Mobile Media Smoking Cessation Service for Young Adults in South Texas:
      Operation and Cost-Effectiveness Estimation.
AB  - To realize the promising potential of services delivered via smart phones to help
      young adults quit smoking at a high level of cost-efficiency, we constructed a
      texting and mobile media system that was promoted in South Texas via social media
      advertising and other recruitment channels. During the 6-month service period
      described here, enrollments were achieved for 798 participants with a mean age of
      29.3 years. Seven-month texted follow-up found that 21% (171) of the enrollees
      reported abstinence at that point. This is consistent with high rates of success
      found in studies of telephone counseling for young adults and confirms that text
      and mobile media service specifically designed for young adults provide a
      feasible and potentially cost-effective approach to promoting cessation.

PMID- 28438056
TI  - Mass spectrometry analysis for amyloidosis typing - is the future bright for its
      clinical implementation?

PMID- 28438057
TI  - The Art of Electrosurgery: Trainees and Experts.
AB  - The benefits of electrosurgery have been acknowledged since the early 1920s, and
      nowadays more than 80% of surgical procedures involve devices that apply energy
      to tissues. Despite its widespread use, it is currently unknown how the
      operator's choices with regard to instrument selection and application technique
      are related to complications. As such, the manner in which electrosurgery is
      applied can have a serious influence on the outcome of the procedure and the well
      being of patients. The aim of this study is to investigate the variety of
      differences in usage of electrosurgical devices. Our approach is to measure these
      parameters to provide insight into application techniques. A sensor was developed
      that records the magnitude of electric current delivered to an electrosurgical
      device at a frequency of 10 Hz. The sensor is able to detect device activation
      times and a reliable estimate of the power-level settings. Data were recorded for
      91 laparoscopic cholecystectomies performed by different surgeons and residents.
      Results of the current measurement data show differences in the way
      electrosurgery is applied by surgeons and residents during a laparoscopic
      cholecystectomy. Variations are seen in the number of activations, the activation
      time, and the approach for removal of the gallbladder. Analysis showed that
      experienced surgeons have a longer activation time than residents (3.01 vs 1.41
      seconds, P < .001) and a lower number of activations (102 vs 123). This method
      offers the opportunity to relate application techniques to clinical outcome and
      to provide input for the development of a best practice model.

PMID- 28438060
TI  - Perceptions of a multidisciplinary team regarding a pediatric rehabilitation
      modified needs assessment.
AB  - BACKGROUND: Efficient service delivery models that optimize processes and human
      resources are required in the current health care climate. A family-centered care
      approach is recognized as a model that can improve the effectiveness and
      efficiency of pediatric rehabilitation. The objective of this study was to
      explore the perceptions of a multidisciplinary health care team regarding the use
      of the Preparation au plan d'intervention (PAPI), a modified needs assessment
      tool designed to facilitate a family-centered care approach among children with
      cerebral motor deficits (CMD) and their families. METHODS: One focus group was
      conducted with the multidisciplinary team (n = 10) of the CMD program at a
      pediatric rehabilitation center. It was audio recorded and transcribed verbatim
      for content analysis. RESULTS: Three overarching themes were identified from the
      analyzes: (1) a facilitator of open communication, (2) a way to gain the unique
      sense of the child and family and (3) parents as the experts of their child.
      CONCLUSIONS: Health care professionals value the use of the PAPI as a way of
      facilitating a family-centered care plan process, specifically with children with
      cerebral motor deficits.

PMID- 28438063
TI  - Measuring the Needs of Family Caregivers of People With Dementia: An Assessment
      of Current Methodological Strategies and Key Recommendations.
AB  - While dementia caregivers are regarded as a population with high unmet needs,
      there is little consensus as to how caregivers' needs should be conceptualized
      and measured. This article describes how dementia caregivers' needs are currently
      assessed in the scientific literature with the goal of suggesting guidelines for
      the enhancement of future measurement of caregiver needs. A review of 26 articles
      identified overarching themes within measurement approaches including variation
      in methodological rigor, proxy indicators of need, dual needs assessment of
      caregiver and person with dementia (PWD), and third-party needs assessment. We
      recommend future research dedicate theoretical attention to the conceptualization
      and classification of caregivers' needs to build a stronger foundation for
      measurement. The measurement development process should capitalize on mixed
      methodology and follow instrument development and validation guidelines set forth
      by measurement theory. Reliable and valid instruments are essential to developing
      services and policies that address dementia caregivers' needs.

PMID- 28438061
TI  - The pattern and magnitude of "in vivo thrombin generation" differ in women with
      preeclampsia and in those with SGA fetuses without preeclampsia.
AB  - OBJECTIVE: We aimed to determine the differences in the pattern and magnitude of
      thrombin generation between patients with preeclampsia (PE) and those with a
      small-for-gestational-age (SGA) fetus. METHODS: This cross-sectional study
      included women in the following groups: (1) normal pregnancy (NP) (n = 49); (2)
      PE (n = 56); and (3) SGA (n = 28). Maternal plasma thrombin generation (TGA) was
      measured, calculating: (a) lag time (LT); (b) velocity index (VI); (c) peak
      thrombin concentration (PTC); (d) time-to-peak thrombin concentration (TPTC); and
      (e) endogenous thrombin potential (ETP). RESULTS: (1) The median TPTC, VI, and
      ETP differed among the groups (p = .001, p = .006, p < .0001); 2) the median ETP
      was higher in the PE than in the NP (p < .0001) and SGA (p = .02) groups; 3)
      patients with SGA had a shorter median TPTC and a higher median VI than the NP (p
      = .002, p = .012) and PE (p < .0001, p = .006) groups. CONCLUSIONS: (1) Patients
      with PE had higher in vivo thrombin generation than women with NP and those with
      an SGA fetus; (2) the difference in TGA patterns between PE and SGA suggests that
      the latter group had faster TGA, while patients with PE had a longer reaction,
      generating more thrombin. This observation is important for the identification of
      a subset of patients who might benefit from low molecular-weight heparin.

PMID- 28438062
TI  - Associations of maternal obesity and smoking status with perinatal outcomes.
AB  - Maternal obesity and smoking are associated with adverse perinatal outcomes.
      These prevalent conditions contribute to health disparities. In this study, we
      examine whether maternal BMI moderates the impact of smoking cessation on short
      term perinatal outcomes. This is a secondary analysis of assessments conducted
      from several prospective clinical trials examining the efficacy of incentives to
      promote smoking cessation during pregnancy. Participants were randomly assigned
      to receive financial incentives contingent upon smoking abstinence or a control
      condition. Pregnancy outcomes were abstracted from the medical record. ANCOVA and
      multiple logistic regression were used for statistical analysis. Among 388 women,
      there was a significant interaction between maternal pre-pregnancy BMI and
      smoking status on gestational age at delivery (p = .03) and admission to the NICU
      (p = .04). Among underweight/normal weight gravidas, smoking resulted in earlier
      deliveries and a greater likelihood of NICU admission than in those who
      abstained. Among overweight/obese gravidas, there was no effect of smoking on
      gestational age at delivery and infants of smokers were less likely to be
      admitted to the NICU. Maternal obesity and smoking have significant individual
      effects on perinatal outcome. Maternal overweight/obesity appears to moderate the
      effect of smoking on gestational age at delivery and on NICU admissions.

PMID- 28438064
TI  - Utility of fetal cardiac magnetic resonance imaging to assess fetuses with right
      aortic arch and right ductus arteriosus.
AB  - OBJECTIVE: To evaluate the utility of fetal cardiac magnetic resonance imaging
      (MRI) to diagnose right aortic arch (RAA) with right ductus arteriosus. METHODS:
      This retrospective study included six fetuses with right aortic arch and right
      ductus arteriosus. The six fetal cases were examined using a 1.5-T magnetic
      resonance unit. The steady-state free precession (SSFP) and single-shot turbo
      spin echo (SSTSE) sequences were used to evaluate the fetal heart and airway. The
      gestational age of the six fetuses ranged from 22 to 35 weeks (mean, 26.5 weeks).
      The age of the pregnant women ranged from 23 to 40 years (mean 31 years).
      RESULTS: Fetal cardiac MRI diagnosed the six fetal cases with RAA with right
      ductus arteriosus correctly. Among the six fetuses, four were associated with
      other congenital heart defects. In three of six cases, the diagnoses established
      using prenatal echocardiography (echo) was correct when compared with postnatal
      diagnosis. CONCLUSIONS: Fetal cardiac MRI is a useful complementary tool to
      assess fetuses with RAA and right ductus arteriosus.

PMID- 28438065
TI  - Reduced Expression of Eukaryotic Translation Initiation Factor 3 Subunit e and
      Its Possible Involvement in the Epithelial-Mesenchymal Transition in
      Endometriosis.
AB  - Epithelial-mesenchymal transition (EMT) is now well documented to be involved in
      the development of endometriosis through the promotion of invasion and
      fibrogenesis. To date, several factors have been reported to be involved in EMT
      in endometriosis. The eukaryotic translation initiation factor 3 subunit e
      (eIF3e) protein is a component of the multisubunit eIF3 complex essential for cap
      dependent translation initiation. The aim of this study was to investigate
      whether eIF3e is involved in EMT in endometriosis. We recruited 40 premenopausal
      women (34.7 [6.8] years) with laparoscopically and histologically diagnosed
      ovarian endometriomas, and their ectopic endometrial tissue samples were
      collected after informed consent. As controls, endometrial tissue samples were
      obtained after informed consent from 40 premenopausal women, roughly age-matched
      (36.9 [6.4] years) and menstrual phase-matched with endometriosis group, who
      underwent surgery for benign gynecologic disorders or cervical intraepithelial
      neoplasia but without endometriosis, adenomyosis, or uterine fibroids. All tissue
      samples were subjected to immunohistochemistry analysis of eIF3e, transforming
      growth factor (TGF-beta1), Snail, E-cadherin, vimentin, and proliferating cell
      nuclear antigen (PCNA). We found significantly reduced immunoreactivity against
      eIF3e and E-cadherin but elevated immunoreactivity against TGF-beta1, Snail,
      vimentin, and PCNA in endometriotic epithelial cells when compared to that of
      control endometrium (all P values <.05). The eIF3e staining levels correlated
      negatively with that of TGF-beta1 and Snail but positively with that of E
      cadherin (all P values <.05). These data suggest that eIF3e downregulation may be
      involved in EMT in endometriosis, possibly through preferential translation of
      Snail. Future studies are warranted to confirm whether this is the mechanism.

PMID- 28438066
TI  - Angiogenesis inhibitors in tackling recurrent glioblastoma.
AB  - INTRODUCTION: Despite aggressive multimodality treatment of glioblastoma, outcome
      remains poor and patients mostly die of local recurrences. Besides reoperation
      and occasionally reirradiation, systemic treatment of recurrent glioblastoma
      consists of alkylating chemotherapy (lomustine, temozolomide), bevacizumab and
      combinations thereof. Unfortunately, antiangiogenic agents failed to improve
      survival either as a monotherapy or in combination treatments. This review
      provides current insights into tumor-derived escape mechanisms and other areas of
      treatment failure of antiangiogenic agents in glioblastoma. Areas covered: We
      summarize the current literature on antiangiogenic agents in the treatment of
      glioblastoma, with a focus on recurrent disease. A literature search was
      performed using the terms 'glioblastoma', 'bevacizumab', 'antiangiogenic',
      'angiogenesis', 'resistance', 'radiotherapy', 'chemotherapy' and derivations
      thereof. Expert commentary: New insights in glioma neoangiogenesis, increasing
      understanding of vascular pathway escape mechanisms, and upcoming immunotherapy
      approaches might revitalize the therapeutic potential of antiangiogenic agents
      against glioblastoma, although with a different treatment intention. The
      combination of antiangiogenic approaches with or without radiotherapy might still
      hold promise to complement the therapeutic armamentarium of fighting
      glioblastoma.

PMID- 28438067
TI  - Gene therapy for patients with advanced solid tumors: a phase I study using gene
      electrotransfer to muscle with the integrin inhibitor plasmid AMEP.
AB  - BACKGROUND: Gene electrotrotransfer describes the use of electric pulses to
      transfer DNA to cells. Particularly skeletal muscle has potential for systemic
      secretion of therapeutic proteins. Gene electrotransfer to muscle using the
      integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide) was
      investigated in a phase I dose escalation study. Primary objective was safety.
      MATERIAL AND METHODS: Patients with metastatic or locally advanced solid tumors,
      without further standard treatments available, were treated with once-only gene
      electrotransfer of plasmid AMEP to the femoral muscle. Safety was monitored by
      adverse events registration, visual analog scale (VAS) after procedure and
      magnetic resonance imaging (MRI) of treated muscles. Pharmacokinetics of plasmid
      AMEP in plasma and urine was determined by quantitative polymerase chain
      reaction. Response was evaluated by positron emission tomography-computed
      tomography (PET-CT) scans. RESULTS: Seven patients were enrolled and treated at
      dose levels from 50 to 250 MUg of plasmid AMEP, the study was terminated early
      due to cessation of plasmid production. Minimal systemic toxicity was observed
      and only transient mild pain was associated with the delivery of the electric
      pulses. MRI of the treated muscles revealed discrete intramuscular edema 24 h
      after treatment. The changes in the muscle tissue resolved within 2 weeks after
      treatment. Peak concentrations of plasmid AMEP was detected only in plasma within
      the first 24 hours after injection. Protein AMEP could not be detected, which
      could be due to the limit of detection. No objective responses were seen.
      CONCLUSIONS: Gene electrotransfer of plasmid AMEP was found to be safe and
      tolerable. No objective responses were observed but other DNA drugs may be tested
      in the future using this procedure.

PMID- 28438068
TI  - High-Definition Video System for Peripheral Neurorrhaphy in Rats.
AB  - BACKGROUND: Although all microsurgeries are based on the use of surgical
      microscopes, several alternative magnification systems have shown promising
      results. Improvements in image quality facilitated the use of video systems in
      microsurgeries with safety and accuracy. The aim of this study was to evaluate
      the use of a low-cost, video-assisted magnification system in peripheral
      neurorrhaphy in rats. METHODS: Twenty Wistar rats were randomly divided into 2
      matched groups according to the magnification system used: the microscope group,
      with neurorrhaphy performed under a microscope with an image magnification of
      40*; and the video system group, with the procedures performed under a video
      system composed of a high-definition Sony camcorder DCR-SR42 set to 52*
      magnification, macro lenses, 42-inch television, and a digital HDMI cable. We
      analyzed weight, nerve caliber, total surgery time, neurorrhaphy time, number of
      stitches, and number of axons in both ends (proximal and distal). RESULTS: There
      were no significant differences between groups in weight, nerve caliber, or
      number of stitches. Neurorrhaphy under the video system took longer (video: 5.60
      minutes; microscope: 3.20 minutes; P < .05). Number of axons was similar between
      groups, both in proximal and distal stumps. CONCLUSION: It is possible to perform
      a peripheral neurorrhaphy in rats through video system magnification, but with a
      longer surgical time.

PMID- 28438069
TI  - Emerging graft protective strategies in clinical liver transplantation.
AB  - INTRODUCTION: There have been remarkable efforts to characterize the key
      responsible pathophysiologic mechanisms, as well as to ameliorate the organ
      preservation and ischemia reperfusion injury with the ultimate goal of expanding
      the donor pool and further improvement of the outcomes of liver transplantation.
      Attempts to translate the experimental results from bench to bedside have yielded
      no valid protective concepts in the field of clinical liver transplantation yet.
      Nonetheless, there has been a considerable amount of ongoing clinical research to
      develop clinically relevant graft protective strategies. Areas covered: This
      review focuses on the most recent evidence based findings and ongoing clinical
      trials that might lead to emerging graft protective strategies in the field of
      clinical liver transplantation. New evidence-based findings in the donor
      preconditioning, organ preservation, and perioperative pharmacologic graft
      protection strategies in the recipient are reviewed. Expert commentary: Few
      strategies have been shown to exert some graft protective effects against
      ischemia reperfusion injury in recent clinical trials in liver transplantation.
      Among others, 'dynamic graft preservation' techniques have been emerging as more
      promising graft optimization strategies.

PMID- 28438070
TI  - Creation of a novel simulator for minimally invasive neurosurgery: fusion of 3D
      printing and special effects.
AB  - OBJECTIVE Recent advances in optics and miniaturization have enabled the
      development of a growing number of minimally invasive procedures, yet innovative
      training methods for the use of these techniques remain lacking. Conventional
      teaching models, including cadavers and physical trainers as well as virtual
      reality platforms, are often expensive and ineffective. Newly developed 3D
      printing technologies can recreate patient-specific anatomy, but the stiffness of
      the materials limits fidelity to real-life surgical situations. Hollywood special
      effects techniques can create ultrarealistic features, including lifelike tactile
      properties, to enhance accuracy and effectiveness of the surgical models. The
      authors created a highly realistic model of a pediatric patient with
      hydrocephalus via a unique combination of 3D printing and special effects
      techniques and validated the use of this model in training neurosurgery fellows
      and residents to perform endoscopic third ventriculostomy (ETV), an effective
      minimally invasive method increasingly used in treating hydrocephalus. METHODS A
      full-scale reproduction of the head of a 14-year-old adolescent patient with
      hydrocephalus, including external physical details and internal neuroanatomy, was
      developed via a unique collaboration of neurosurgeons, simulation engineers, and
      a group of special effects experts. The model contains "plug-and-play"
      replaceable components for repetitive practice. The appearance of the training
      model (face validity) and the reproducibility of the ETV training procedure
      (content validity) were assessed by neurosurgery fellows and residents of
      different experience levels based on a 14-item Likert-like questionnaire. The
      usefulness of the training model for evaluating the performance of the trainees
      at different levels of experience (construct validity) was measured by blinded
      observers using the Objective Structured Assessment of Technical Skills (OSATS)
      scale for the performance of ETV. RESULTS A combination of 3D printing technology
      and casting processes led to the creation of realistic surgical models that
      include high-fidelity reproductions of the anatomical features of hydrocephalus
      and allow for the performance of ETV for training purposes. The models reproduced
      the pulsations of the basilar artery, ventricles, and cerebrospinal fluid (CSF),
      thus simulating the experience of performing ETV on an actual patient. The
      results of the 14-item questionnaire showed limited variability among
      participants' scores, and the neurosurgery fellows and residents gave the models
      consistently high ratings for face and content validity. The mean score for the
      content validity questions (4.88) was higher than the mean score for face
      validity (4.69) (p = 0.03). On construct validity scores, the blinded observers
      rated performance of fellows significantly higher than that of residents,
      indicating that the model provided a means to distinguish between novice and
      expert surgical skills. CONCLUSIONS A plug-and-play lifelike ETV training model
      was developed through a combination of 3D printing and special effects
      techniques, providing both anatomical and haptic accuracy. Such simulators offer
      opportunities to accelerate the development of expertise with respect to new and
      novel procedures as well as iterate new surgical approaches and innovations, thus
      allowing novice neurosurgeons to gain valuable experience in surgical techniques
      without exposing patients to risk of harm.

PMID- 28438071
TI  - Time to re-evaluate ART protocols in the light of advances in knowledge about
      methylation and epigenetics: an opinion paper.
AB  - DNA methylation is a biochemical process that modifies gene expression without
      changing the underlying DNA sequence, and this represents the molecular basis for
      imprinting and epigenetics. Recent reports have revealed alterations in DNA
      methylation profiles in the placenta of babies born from assisted reproductive
      technologies (ART). This supports several previous observations that suggested an
      increase in the prevalence of imprinting diseases following ART treatment, and
      also fits our observations regarding the metabolism and requirements of early
      human embryos. Human embryo culture media (HECM) are currently formulated
      according to requirements based on the mouse embryo model, and in fact need to
      pass the Mouse Embryo Assay test in order to be accepted by the relevant
      authorities, despite the fact that physiological (especially the time necessary
      to reach genomic activation) and biochemical requirements of mouse and human
      embryos are quite different. This commentary aims to explain some of the
      discrepancies, and emphasize why human embryo metabolism tells us that the
      composition of HECM, as well as the role of the MEA as a unique model, should be
      re-evaluated.

PMID- 28438072
TI  - Facial expressions as performances in mime.
AB  - That facial expressions are universal emotion signals has been supported by
      observers agreeing on the emotion mimed by actors. We show that actors can mime a
      diverse range of states: emotions, cognitions, physical states, and actions.
      English, Hindi, and Malayalam speakers (N = 1200) viewed 25 video clips and
      indicated the state conveyed. Within each language, at least 23 of the 25 clips
      were recognised above chance and base rate. Facial expressions of emotions are
      not special in their recognisability, and it is miming that may be the universal
      human ability.

PMID- 28438073
TI  - The meaning profiles of anxiety and depression: similarities and differences in
      two age groups.
AB  - The distinctiveness of anxiety and depression is discussed concerning their
      nature, definitions, uses, manifestations and determinants. The objective was to
      examine the difference and similarity of anxiety and depression by applying the
      psychosemantic approach, which is a theory and methodology based on analysing the
      cognitive processes applied in communicating meanings. In Study 1, there were 760
      participants of both genders, 23-31 years old. They were administered the
      Meanings Test, which yields the respondent's meaning profile, and one of seven
      anxiety scales or one of three depression scales. Significant correlations
      between the meaning profiles and the anxiety or depression scales were summarised
      and compared. In Study 2, there were 78 individuals over 65 years old who were
      administered the Meanings Test plus an anxiety or depression scale. The findings
      for anxiety and depression were compared within and across age groups. The
      results yielded two distinct meaning profiles for anxiety and depression in the
      two age groups. The anxiety profile indicated more focusing on one's internal
      world. whereas the depression profile indicated focusing both on the personal and
      the interpersonally shared reality. The conclusion was that anxiety and
      depression are different constructs that need to be considered as separate
      theoretically and practically.

PMID- 28438074
TI  - The value of metaphorical reasoning in bioethics: An empirical-ethical study.
AB  - BACKGROUND: Metaphors are often used within the context of ethics and healthcare
      but have hardly been explored in relation to moral reasoning. OBJECTIVE: To
      describe a central set of metaphors in one case and to explore their contribution
      to moral reasoning. METHOD: Semi-structured interviews were conducted with 16
      parents of a child suffering from the neurodegenerative disease CLN3. The
      interviews were recorded, transcribed, and metaphors were analyzed. The
      researchers wrote memos and discussed about their analyses until they reached
      consensus. Ethical considerations: Participants gave oral and written consent and
      their confidentiality and anonymity were respected. FINDINGS: A central set of
      metaphors referred to the semantic field of the hands and arms and consisted of
      two central metaphors that existed in a dialectical relationship: grasping versus
      letting go. Participants used these metaphors to describe their child's
      experiences, who had to "let go" of abilities, while "clinging" to structures and
      the relationship with their parent(s). They also used it to describe their own
      experiences: participants tried to "grab" the good moments with their child and
      had to "let go" of their child when (s)he approached death. Participants, in
      addition, "held" onto caring for their child while being confronted with the
      necessity to "let go" of this care, leaving it to professional caregivers.
      DISCUSSION: The ethical analysis of the findings shows that thinking in terms of
      the dialectical relationship between "grasping" and "letting go" helps
      professional caregivers to critically think about images of good care for
      children with CLN3. It also helps them to bear witness to the vulnerable,
      dependent, and embodied nature of the moral self of children with CLN3 and their
      parents. CONCLUSION: Metaphorical reasoning may support the inclusion of
      marginalized perspectives in moral reasoning. Future studies should further
      explore the contribution of metaphorical reasoning to moral reasoning in other
      cases.

PMID- 28438075
TI  - Concomitant Presence of EGFR and ALK Fusion Gene Mutation in Adenocarcinoma of
      Lung: A Case Report and Review of the Literature.
AB  - Empirical evidence has long suggested that oncogenic driver mutations in non
      small-cell lung cancer are mutually independent. However, recent studies reported
      in pertinent literature reveal that concomitant epidermal growth factor receptor
      (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement can occur in
      a subset of patients with NSCLC. In order to shed further light on this issue, we
      report a case of adenocarcinoma of lung harboring both EGFR mutation in exon 21
      (L861Q) and ALK rearrangement. This allows us to speculate on likely molecular
      mechanisms underlying this uncommon phenomenon, while also offering some
      practical guidelines on the therapeutic options that could benefit patients
      diagnosed with this dual-positive tumor.

PMID- 28438076
TI  - Increased work and social engagement is associated with increased stroke specific
      quality of life in stroke survivors at 3 months and 12 months post-stroke: a
      longitudinal study of an Australian stroke cohort.
AB  - BACKGROUND: There is a relative lack of longitudinal studies investigating stroke
      specific outcomes and quality of life (QOL). This study aimed to identify which
      factors (level of disability, cognitive functioning, depressive symptoms,
      physical activity, and work and social engagement) were independently associated
      with each stroke-specific domain of QOL, adjusting for age and gender, at 3
      months and 12 months post-stroke in an Australian cohort. METHOD: Survivors of
      ischemic stroke were recruited from 18 sites of the STroke imAging pRevention and
      Treatment (START) longitudinal cohort study. Survivors were assessed at 3 months
      (n = 185) and 12 months (n = 170) post-stroke using the Stroke Impact Scale
      (SIS), modified Rankin Scale (mRS), Montreal Cognitive Assessment (MoCA),
      Montgomery-Asberg Depression Rating Scale, Rapid Assessment of Physical Activity,
      and Work and Social Adjustment Scale (WSAS). RESULTS: WSAS was independently
      associated with the SIS domains of: Physical Composite function; Participation;
      and Perceived Recovery at 3 months and 12 months and SIS domain of Emotion at 12
      months post-stroke. The presence of depressive symptoms was independently
      associated with the SIS domains of: Memory and Thinking; and Emotion at 3 months.
      At 12 months post-stroke, mRS was independently associated with SIS domain of
      Physical Composite function and MoCA with SIS domain of Communication.
      CONCLUSION: Engaging in work and social activities is an important factor
      associated with stroke-specific domains of QOL over time. It is recommended that
      services focus on improving work and social engagement given their importance
      related to QOL in the first year of recovery post-stroke. Identifying and
      treating those with depressive symptoms may enhance QOL in the early months post
      stroke. TRIAL REGISTRATION: START-PrePARE Australian New Zealand Clinical Trials,
      www.anzctr.org.au , Registry number: ACTRN12610000987066. EXTEND
      ClinicalTrial.gov identifier: NCT00887328.

PMID- 28438077
TI  - Molecular dynamics simulations reveal the influence of dextran sulfate in
      nanoparticle formation with calcium alginate to encapsulate insulin.

PMID- 28438078
TI  - Ten-year follow-up of a case of necrotizing fasciitis successfully treated with
      negative-pressure wound therapy, dermal regeneration template application, and
      split- thickness skin autograft.
AB  - INTRODUCTION: Necrotizing fasciitis is a rapidly progressive and often fatal
      infection of the fasciae and subcutaneous tissues. PATIENT AND METHODS: In this
      case report, we present the treatment of a 63-year-old patient suffering from
      diabetes mellitus, who was admitted to the emergency unit for severe right
      gluteal pain, which had begun 24 hours before admission. Cutaneous symptoms,
      oliguria, metabolic acidosis, acute renal failure, severe hypotension, and
      tachycardia occurred, and the patient was admitted to Intensive Care a few hours
      after initial admission. The patient underwent a debridement of gluteal,
      abdominal, lower-thoracic, and upper thigh regions. Biopsy of fascia lata
      confirmed the suspected diagnosis of necrotizing fasciitis. Treatment included
      prompt surgical debridement, negative-pressure wound therapy, and dermal
      regeneration template application with fibrin glue, and subsequent split
      thickness skin autografting. RESULTS: After 10 years, elasticity of the skin and
      limb mobility are comparable to that in non-injured areas, and the patient is
      pain free. CONCLUSION: In our opinion, this combination should be a treatment of
      choice for large wounds in the patients with NF with multiple comorbidities.

PMID- 28438079
TI  - Potential Noncutaneous Sites of Chelonid Herpesvirus 5 Persistence and Shedding
      in Green Sea Turtles Chelonia mydas.
AB  - Chelonid herpesvirus 5 (ChHV5), the likely etiologic agent of sea turtle
      fibropapillomatosis (FP), is predicted to be unevenly distributed within an
      infected turtle, in which productive virus replication and virion shedding occurs
      in cutaneous tumor keratinocytes. In this study, we measured and compared ChHV5
      DNA quantities in tumors, skin, urine, major organs, and nervous tissue samples
      from green turtles Chelonia mydas. These samples were taken from the carcasses of
      10 juvenile green turtles with and without clinical signs of FP that stranded in
      Florida during 2014. Quantitative PCR for ChHV5 UL30 was used to identify ChHV5
      DNA in tumors, skin, heart, kidney, nerves, and urine sampled from five out of
      five FP-positive and three out of five FP-free turtles. The most frequently co
      occurring sites were cutaneous tumor and kidney (n = 4). Novel data presented
      here include the identification of ChHV5 DNA in kidney, heart, and nerve samples
      from three FP-free turtles. These data support candidate nontumored anatomic
      sites of ChHV5 DNA localization and mobilization during two different disease
      states that may be involved in the ChHV5 infection cycle. Received September 8,
      2016; accepted April 17, 2017.

PMID- 28438081
TI  - Long-term operation of Kickuth-type constructed wetland applied to municipal
      wastewater treatment in temperate climate.
AB  - The purpose of this paper is to discuss the problem of changes of effectiveness
      of Kickuth-type constructed wetland with subsurface flow applied to domestic
      wastewater treatment. This study is based on an example of a wetland 3000 m2 in
      surface, serving 800 inhabitants, located in Poland. The results of chemical
      analysis showed that after an initial year of 'start-up time', the efficiency of
      pollutant removal gradually increased to reach an apex in the 6th year of
      operation. Such maximum efficiency continued up to the 10th year of operation;
      afterwards it gradually dropped. Moreover, after 12 years of operation, a serious
      problem with overland flow was observed, which indicated the porous media
      clogging processes.

PMID- 28438080
TI  - Guillain-Barre syndrome in pregnancy: A case report.
AB  - Guillain-Barre syndrome is a rare condition in pregnancy which is characterised
      by symmetrical progressive ascending polyneuropathy. A case of a 16-year-old
      nulliparous woman who presented with rapidly progressive limb paralysis following
      an upper respiratory tract infection a week prior to presentation is discussed.
      She was intubated as she had developed respiratory failure and managed in the
      intensive care unit by a multidisciplinary team. Plasma exchange and intravenous
      immunoglobulin were not readily available so she was managed conservatively. The
      management of Guillain-Barre syndrome, maternal and foetal outcomes have been
      discussed.

PMID- 28438082
TI  - Radioimmunoconjugates for treating cancer: recent advances and current
      opportunities.
AB  - INTRODUCTION: Radioimmunoconjugates have been used for 30 years to diagnose and
      treat cancer. For many years, the use of these therapeutic tools has been limited
      to haematological disorders, such as non-Hodgkin's lymphoma, given that they have
      only had a moderate effect on solid tumours. Areas covered: Recently, several
      strategies have revived the potential therapeutic application for
      radioimmunoconjugates. In this review, the authors review the advances in
      immunological engineering to develop new tools like monoclonal antibodies and
      their derivatives. Then, the authors summarize the development of radionuclides,
      the use of recombinant antibodies, pretargeting approaches, and dose
      fractionation techniques, providing opportunities for both therapeutic and
      diagnostic applications. Expert opinion: Radioimmunoconjugates used in nuclear
      medicine have entered a new era of development. These advances give rise to a
      variety of opportunities in the management of various cancers, where the
      radiolabelled antibodies may be particularly useful in immuno-specific phenotypic
      imaging e.g. companion diagnostics. Concerning therapeutic applications,
      radioimmunoconjugates have demonstrated their efficacy in the treatment of both
      haematological malignancies and solid tumours. Recent procedural developments are
      of great interest in optimising oncological targeted therapies. In the field of
      cancer theranostics, we believe that radioimmunoconjugated compounds are likely
      to play a large part in near future.

PMID- 28438083
TI  - Supplemental feeding of a gut microbial metabolite of linoleic acid, 10-hydroxy
      cis-12-octadecenoic acid, alleviates spontaneous atopic dermatitis and modulates
      intestinal microbiota in NC/nga mice.
AB  - The present study investigated the antiallergic and anti-inflammatory effects of
      10-hydroxy-cis-12-octadecenoic acid (HYA), a novel gut microbial metabolite of
      linoleic acid, in NC/Nga mice, a model of atopic dermatitis (AD). Feeding HYA
      decreased the plasma immunoglobulin E level and skin infiltration of mast cells
      with a concomitant decrease in dermatitis score. HYA feeding decreased TNF-alpha
      and increased claudin-1, a tight junction protein, levels in the mouse skin.
      Cytokine expression levels in the skin and intestinal Peyer's patches cells
      suggested that HYA improved the Th1/Th2 balance in mice. Immunoglobulin A
      concentration in the feces of the HYA-fed mice was approximately four times
      higher than that in the control mice. Finally, denaturing gradient gel
      electrophoresis of the PCR-amplified 16 S rRNA gene of fecal microbes indicated
      the modification of microbiota by HYA. Taken together, the alterations in the
      intestinal microbiota might be, at least in part, associated with the
      antiallergic effect of HYA.

PMID- 28438084
TI  - History and mysteries of leprosy.

PMID- 28438085
TI  - The feline blood film.
AB  - Practical relevance: Many veterinary practices have invested in quality automated
      hematology instruments for use in-house. However, regardless of the specific
      choice of analyzer, there are important hematology findings that can only be
      determined by microscopic examination of stained blood films. For this reason,
      and also for the purpose of quality control for the analyzer, a quick blood film
      review should be performed alongside every automated complete blood count. Even
      those practices that submit their blood samples to outside diagnostic
      laboratories for evaluation, still require the capability to examine stained
      blood films in emergency situations. Series outline: This is the first of a two
      part article series that aims to familiarize the practitioner with normal
      findings on feline blood films, with a particular focus on unique features in the
      cat, as well as to assist with interpretation of common abnormalities. Part 1
      focuses on how to prepare and examine blood films in order to maximize the
      reliability of the information they convey, and describes the morphology of
      feline erythrocytes in health and disease. Evidence base: The information and
      guidance offered is based on the published literature and the author's own
      extensive clinical pathology research.

PMID- 28438086
TI  - Feline leprosy due to Candidatus 'Mycobacterium tarwinense':Further clinical and
      molecular characterisation of 15 previously reported cases and an additional 27
      cases
AB  - OBJECTIVES: This paper, the first in a series of three on 'feline leprosy',
      provides a detailed description of disease referable to Candidatus 'Mycobacterium
      tarwinense', the most common cause of feline leprosy in Victoria, Australia.
      METHODS: Cases were sourced retrospectively and prospectively for this
      observational study, describing clinical, geographical and molecular
      microbiological data for cats definitively diagnosed with Candidatus 'M
      tarwinense' infection. RESULTS: A total of 145 cases of feline leprosy were
      scrutinised; 114 'new' cases were sourced from the Victorian Infectious Diseases
      Reference Laboratory records, veterinary pathology laboratories or veterinarians,
      and 31 cases were derived from six published studies. Forty-two cats were
      definitively diagnosed with Candidatus 'M tarwinense' infection. Typically, cats
      were between 3 and 11 years of age, with no gender predilection, and were
      generally systemically well. All had outdoor access. Most cats underwent surgical
      resection of lesions with adjunctive medical therapy, often utilising a
      combination of oral clarithromycin and rifampicin for at least 3 months.
      Prognosis for recovery was generally good. Resolution of lesions was not observed
      in the absence of treatment, but a number of untreated cats continued to enjoy an
      acceptable quality of life despite persistence of the disease, which extended
      locally but did not appear to disseminate to internal organs. Preliminary results
      of draft genome sequencing confirmed that the species is a member of the
      Mycobacterium simiae complex. CONCLUSIONS AND RELEVANCE: Candidatus 'M
      tarwinense', a fastidious member of the M simiae complex, is capable of causing
      feline leprosy with a tendency to produce lesions on the head, particularly
      involving the eyes and periocular skin. The disease has an indolent clinical
      course and generally responds favourably to therapy despite lesions often
      containing large numbers of organisms. Detailed genomic analysis may yield clues
      as to the environmental niche and culture requirement of this elusive organism.
      Prospective treatment trials and/or drug susceptibility testing in specialised
      systems would further inform treatment recommendations.

PMID- 28438087
TI  - News & Views.

PMID- 28438088
TI  - Anaplasma, Ehrlichia and Rickettsia species infections in cats: European
      guidelines from the ABCD on prevention and management
AB  - OVERVIEW: Anaplasma species, Ehrlichia species and Rickettsia species are vector
      borne pathogens infecting a wide variety of mammals, but causing disease in very
      few of them. Infection in cats: Anaplasma phagocytophilum is the most important
      feline pathogen among these rickettsial organisms, and coinfections are possible.
      Little information is available on the pathogenesis of these agents in cats.
      Clinical signs are usually reported soon after tick infestation. They are mostly
      non-specific, consisting of fever, anorexia and lethargy. Joint pain may occur.
      Infection in humans: Some rickettsial species ( A phagocytophilum, Ehrlichia
      chaffeensis, Ehrlichia ewingii, Rickettsia conorii, Rickettsia rickettsii,
      Rickettsia felis, Rickettsia typhi and Candidatus Neoehrlichia mikurensis) are of
      zoonotic concern. Direct contact with cat saliva should be avoided because of
      potential contamination by R felis. Infected cats are 'sentinels' of the presence
      of rickettsial pathogens in ticks and fleas in a given geographical area, and
      they signal a risk for people exposed to vectors.

PMID- 28438089
TI  - Feline biliary tree and gallbladder disease: Aetiology, diagnosis and treatment
AB  - Practical relevance Diseases of the biliary tree and gallbladder are more common
      in cats than diseases of the liver parenchyma. The parenchyma is usually affected
      secondarily to systemic illnesses, while the biliary system is the prime target
      for infectious agents (eg, bacteria and flukes) and non-infectious conditions
      (eg, neoplasia and cysts). Clinical approaches Cats with biliary disease are
      evaluated because of common feline clinical signs such as anorexia, nausea,
      vomiting and lethargy. Icterus may or may not be obvious. Biopsies for
      histological evaluation, and bile aspirates for culture and cytological
      evaluation are helpful diagnostically. Antibiotics and immunosuppressive drugs
      have been used successfully. Hepatosupportive drugs may help in liquefying thick
      bile and protecting hepatic tissue from damage. Ultrasound is a noninvasive
      diagnostic tool that may help in identifying dilated bile ducts, liver cysts and
      choleliths. It is also used to guide percutaneous bile aspiration. Audience This
      review, written for all veterinarians who treat cats, describes the various
      conditions that can affect the feline biliary tree and gallbladder. Treatment
      options are discussed, and brief summaries provided of surgical techniques and
      diagnostic approaches. Evidence base The veterinary literature pertaining to
      feline biliary disease is comprehensively reviewed. When appropriate, data on
      dogs and humans has been included to provide background information. Based on the
      available literature, more research into feline biliary diseases is needed.

PMID- 28438090
TI  - Laparoscopic ventral hernia repair using a composite mesh with polypropylene and
      expanded polytetrafluoroethylene: a prospective, multicentre registry.
AB  - BACKGROUND: Abdominal wall hernias are a common problem. Composite meshes placed
      intraperitoneally for abdominal wall hernia repair are widely used. This registry
      evaluated the safety and efficacy of one specific composite mesh with
      polypropylene and expanded polytetrafluoroethylene (Intramesh(r) T1) in
      laparoscopic ventral hernia repair. METHODS: A prospective multicentre registry
      with data from seven centres was collected between January 2013 and September
      2014. Primary endpoint was recurrence rate at 12 months determined by clinical
      examination. Secondary outcome measures included intraoperative complications,
      complications during hospitalisation and at 1-month and 12-months follow-up.
      RESULTS: The registry included 90 patients (30 female and 60 male). Fifty-five
      patients (61.1%) presented with primary ventral hernias and 35 patients (38.9%)
      with incisional ventral hernias. Median hernia size was 4 cm2. Intraoperative
      complications were reported in two patients (2.2%). Complications during
      hospitalisation were reported in four (4.4%) patients. At 1-month follow-up, 17
      (18.9%) patients had postoperative complications, of which 5 complications were
      major and 19 were minor. Late complications at 12-months were observed in 10
      patients (11.1%), of which 2 were major and 8 minor complications. CONCLUSION:
      Intramesh(r) T1 is a safe and effective composite mesh with favourable short and
      midterm outcome and morbidity. (NCT01816867).

PMID- 28438091
TI  - Analytic Response Curves of Clinical Breast Cancer IHC Tests.
AB  - An important limitation in the field of immunohistochemistry (IHC) is the
      inability to correlate stain intensity with specific analyte concentrations.
      Clinical immunohistochemical tests are not described in terms of analytic
      response curves, namely, the analyte concentrations in a tissue sample at which
      an immunohistochemical stain (1) is first visible, (2) increases in proportion to
      the analyte concentration, and (3) ultimately approaches a maximum color
      intensity. Using a new immunostaining tool ( IHControls), we measured the
      analytic response curves of the major clinical immunohistochemical tests for
      human epidermal growth factor receptor type II (HER-2), estrogen receptor (ER),
      and progesterone receptor (PR). The IHControls comprise the analytes HER-2, ER,
      and PR at approximately log concentration intervals across the range of
      biological expression, from 100 to 1,000,000 molecules per test microbead. We
      stained IHControls of various concentrations using instruments, reagents, and
      protocols from three major IHC vendors. Stain intensity at each analyte
      concentration was measured, thereby generating an analytic response curve. We
      learned that for HER-2 and PR, there is significant variability in test results
      between clinical kits for samples with analyte concentrations of approximately
      104 molecules/microbead. We propose that the characterization of immunostains is
      an important step toward standardization.

PMID- 28438092
TI  - Characterization by Lectin Histochemistry of Two Subpopulations of Parietal Cells
      in the Rat Gastric Glands.
AB  - Parietal cells undergo a differentiation process while they move from the isthmus
      toward the pits and the base region of the gastric gland. The aim of this work
      was to analyze the rat gastric glands by lectin histochemistry to show the
      glycans expressed by upper (young) and lower (old) parietal cells. We used
      lectins recognizing the most frequent sugar moieties in mammals. Each lectin was
      assayed alone and in combination with several deglycosylation pretreatments: (1)
      beta-elimination, which removes O-linked oligosaccharides; (2) incubation with
      Peptide-N-glycosidase F, to remove N-linked glycans; (3) acid hydrolysis, which
      removes terminal sialic acid moieties; (4) methylation-saponification, to remove
      sulfate groups from sugar residues; and (5) glucose oxidase, a technique carried
      out with the lectin concanavalin A to convert glucose into gluconic acid. The
      lectins from Helix pomatia, Dolichos biflorus (DBA), Glycine max (soybean),
      Maclura pomifera, Arachis hypogaea (peanut), Bandeiraea simplicifolia (lectin I
      B4), and Datura stramonium showed a different glycan expression in the parietal
      cells throughout the gastric gland. This difference supports that parietal cells
      undergo a maturation/degeneration process while the cells descend along the
      gland. The role of DBA as a marker of parietal cells previously reported should
      be taken with caution because these cells showed different reactivity for the
      lectin, ranging from negative to strong labeling.

PMID- 28438093
TI  - Tyramide Signal Amplification Permits Immunohistochemical Analyses of Androgen
      Receptors in the Rat Prefrontal Cortex.
AB  - Research on neural androgen receptors (ARs) has traditionally focused on brain
      regions that regulate reproductive and aggressive behaviors, such as the
      hypothalamus and amygdala. Although many cells in the prefrontal cortex (PFC)
      also express ARs, the number of ARs per cell appears to be much lower, and thus,
      AR immunostaining is often hard to detect and quantify in the PFC. Here, we
      demonstrate that biotin tyramide signal amplification (TSA) dramatically
      increases AR immunoreactivity in the rat brain, including critical regions of the
      PFC such as the medial PFC (mPFC) and orbitofrontal cortex (OFC). We show that
      TSA is useful for AR detection with both chromogenic and immunofluorescent
      immunohistochemistry. Double-labeling studies reveal that AR+ cells in the PFC
      and hippocampus are NeuN+ but not GFAP+ and thus primarily neuronal. Finally, in
      gonadally intact rats, more AR+ cells are present in the mPFC and OFC of males
      than of females. Future studies can use TSA to further examine AR
      immunoreactivity across ages, sexes, strains, and different procedures (e.g.,
      fixation methods). In light of emerging evidence for the androgen regulation of
      executive function and working memory, these results may help understand the
      distribution and roles of ARs in the PFC.

PMID- 28438094
TI  - Association of ATF4 Expression With Tissue Hypoxia and M2 Macrophage Infiltration
      in Infantile Hemangioma.
AB  - Accumulating studies have revealed the hypoxic condition and its crucial role in
      the distinctive progression of infantile hemangioma (IH), the most common benign
      tumor in infancy. Activating transcription factor 4 (ATF4), an important gene
      mediating cellular adaptation to various stress signals, could confer a survival
      advantage for tumor cells under hypoxia and regulate tumor progression. However,
      the potential role of ATF4 in IH was still unknown. In this study, the expression
      of hypoxia inducible factor (HIF)-1alpha, ATF4, and macrophage colony-stimulating
      factor (M-CSF) in 27 specimens of IH was measured by immunochemistry and double
      labeling immunofluorescence, followed by the Spearman rank correlation test. Our
      results showed that the expression of HIF-1alpha, ATF4, and M-CSF was
      significantly upregulated in proliferating IH compared with involuting IH.
      Meanwhile, HIF-1alpha and ATF4, in parallel with ATF4 and M-CSF, exhibited
      positive correlation and synchronous expression. In addition, our in vitro
      studies demonstrated that hypoxia obviously upregulated the expression of HIF
      1alpha, ATF4, and M-CSF in hemangioma stem cells. Most importantly, their
      expression was uniformly correlated with the percentage of M2-polarized
      macrophages in IH. All those results and established evidence indicated that
      hypoxia-induced ATF4 expression may promote progression of proliferating IH
      through M-CSF-induced M2-polarized macrophages infiltration.

PMID- 28438095
TI  - Arcobacter: an emerging food-borne zoonotic pathogen, its public health concerns
      and advances in diagnosis and control - a comprehensive review.
AB  - Arcobacter has emerged as an important food-borne zoonotic pathogen, causing
      sometimes serious infections in humans and animals. Newer species of Arcobacter
      are being incessantly emerging (presently 25 species have been identified) with
      novel information on the evolutionary mechanisms and genetic diversity among
      different Arcobacter species. These have been reported from chickens, domestic
      animals (cattle, pigs, sheep, horses, dogs), reptiles (lizards, snakes and
      chelonians), meat (poultry, pork, goat, lamb, beef, rabbit), vegetables and from
      humans in different countries. Arcobacters are implicated as causative agents of
      diarrhea, mastitis and abortion in animals, while causing bacteremia,
      endocarditis, peritonitis, gastroenteritis and diarrhea in humans. Three species
      including A. butzleri, A. cryaerophilus and A. skirrowii are predominantly
      associated with clinical conditions. Arcobacters are primarily transmitted
      through contaminated food and water sources. Identification of Arcobacter by
      biochemical tests is difficult and isolation remains the gold standard method.
      Current diagnostic advances have provided various molecular methods for efficient
      detection and differentiation of the Arcobacters at genus and species level. To
      overcome the emerging antibiotic resistance problem there is an essential need to
      explore the potential of novel and alternative therapies. Strengthening of the
      diagnostic aspects is also suggested as in most cases Arcobacters goes unnoticed
      and hence the exact epidemiological status remains uncertain. This review updates
      the current knowledge and many aspects of this important food-borne pathogen,
      namely etiology, evolution and emergence, genetic diversity, epidemiology, the
      disease in animals and humans, public health concerns, and advances in its
      diagnosis, prevention and control.

PMID- 28438096
TI  - Venous air embolism: An under-recognised entity in blunt-force trauma and the
      importance of radiology.
AB  - Air embolism (AE) is considered a rare event and can be either iatrogenic or
      traumatic. Various post-mortem methods to detect AE exist, of which radiology is
      preferred. The presence of air in the heart can be demonstrated using special
      dissection techniques where the heart is opened under water or by needle puncture
      from a water-filled syringe. Three cases of blunt-force head injury are presented
      herein, with AE being diagnosed by conventional radiography using a Lodox
      Statscan(r) full-body digital X-ray machine in all cases. This case series
      demonstrates that AE due to blunt-force trauma to the head and sinuses might be
      under-recognised in the forensic post-mortem setting. It also highlights the
      importance of radiology in diagnosing AE post-mortem, especially where the
      results of post-mortem techniques might be unsatisfactory.

PMID- 28438097
TI  - People can die from opiate withdrawal.

PMID- 28438098
TI  - Corrigendum.

PMID- 28438099
TI  - A single-centre review of suspected sudden infant death cases.
AB  - This study aimed to establish the number of deaths in infants under 1 year of age
      that were being reported for medico-legal examination at a single large academic
      centre in Hungary, as well as the method of these investigations with special
      emphasis on histopathology, ancillary techniques and the adherence of our current
      practice to international recommendations. A single-centre, retrospective audit
      was conducted on all suspected sudden infant death cases. After the review there
      were eight infectious background sudden infant death syndrome (SIDS) cases,
      infectious respiratory tract disease in 14 cases, cardiac septal tumour in one
      case, and hepatic, possibly metabolic, disorder in one case. Our study has
      highlighted that even in a single institution there is a huge heterogeneity of
      approaches which needs standardisation. A reclassification of infant cases
      according to the San Diego definition resulted in a decreased number of SIDS
      cases in our material. The San Diego definition and related international
      recommendations were found to be practical and the classification provides a
      guide to the standardisation of current practice.

PMID- 28438100
TI  - An epidemiology of sexual assault among elderly women in the Mthatha area of
      South Africa.
AB  - Background South Africa has one of the highest rates of rape in the world, but
      this barely seems to surprise anyone. It is extremely disturbing, especially when
      children and elderly women are raped. Women and children are usually the weakest
      group in society physically, as well as the most exposed to abuse and neglect. It
      should be the responsibility of a civil society to protect these vulnerable
      groups from harm. Objective This study investigated the trend of rapes among
      elderly women in the Mthatha area of South Africa. Method This was a
      retrospective descriptive study from the records of the Sinawe Centre. All cases
      of the rape of elderly women (i.e. those aged >=65 years) between 2007 and 2011
      were recorded. The Sinawe Centre is now a one-stop centre known as the Thuthuzela
      Sinawe Centre, which is the only centre to deal with cases of rape in this area.
      Results A total 2579 adult victims of rape (i.e. those aged >=16 years) were
      reported at the Sinawe Centre over a five-year period (2007-2011). Of these, 145
      (5.6%) involved elderly women. The average rate of rape among elderly women was
      20.7/10,000 adult women per year. There was an increase in elderly rape from
      17.1/10,000 women in 2007 to 40/10,000 women in 2009. The highest percentage
      (45.5%) of women were aged between 65 and 70 years, and the lowest percentage
      (4.1%) were aged between 86 and 90 years. The highest number of cases (56; 38.6%)
      were reported in 2009 (p < .05; chi2 = 45.2). In the majority of cases (122;
      84.2%), there was a single perpetrator. There were two perpetrators in 14 (9.6%)
      cases, and three or more perpetrators were recorded in nine (6.2%) rapes. A
      little more than half (74; 51%) were known to the victims. In 117 (83%) cases,
      the rape took place in the home. Human immunodeficiency virus infection was found
      to be prevalent in five (3.6%) cases of elderly rape. Conclusion There are a high
      number of rapes among elderly women in the Mthatha area of South Africa. It is a
      matter of serious concern, and needs urgent attention.

PMID- 28438101
TI  - Intravenous administration of cannabis and lethal anaphylaxis.
AB  - Cannabis allergy appears to be increasing. A 33-year-old woman is reported who
      collapsed and died shortly after injecting herself with a cannabis solution
      prepared by pouring boiling water onto plant material. There were no significant
      findings at autopsy, except for a single recent venepuncture wound in the left
      cubital fossa. Toxicological examination of the blood revealed low levels of
      methylamphetamine and amphetamine with tetrahydrocannabinol (Delta9-THC) and 11
      nor-9-carboxy-Delta9-THC, and no opiates. The syringe used by the decedent
      contained Delta9-THC. Serum tryptase levels were markedly elevated (>200 ug/L; N
      < 12 ug/L). This finding coupled with the sudden collapse after injecting an
      aqueous extract of cannabis indicated a likely anaphylactic or anaphylactoid
      reaction to the extract. Cannabis allergy may occur following handling,
      inhalation, swallowing or injecting Cannabis sativa plants or their products. The
      possibility of an allergic reaction should therefore be considered at autopsy in
      deaths where there has been recent contact with cannabis.

PMID- 28438102
TI  - Mapping a Careflow Network to assess the connectedness of Connected Health.
AB  - Connected Health is an emerging and rapidly developing field which has the
      potential to transform healthcare service systems by increasing its safety,
      quality and overall efficiency. From a healthcare perspective, process
      improvement models have mainly focused on the static workflow viewpoint. The
      objective of this article is to study and model the dynamic nature of healthcare
      delivery, allowing us to identify where potential issues exist within the service
      system and to examine how Connected Health technological solutions may support
      service efficiencies. We explore the application of social network analysis (SNA)
      as a modelling technique which captures the dynamic nature of a healthcare
      service. We demonstrate how it can be used to map the 'Careflow Network' and
      guide Connected Health innovators to examine specific opportunities within the
      healthcare service. Our results indicate that healthcare technology must be
      correctly identified and implemented within the Careflow Network to enjoy
      improvements in service delivery. Oftentimes, prior to making the transformation
      to Connected Health, researchers use various modelling techniques that fail to
      identify where Connected Health innovation is best placed in a healthcare service
      network. Using SNA allows us to develop an understanding of the current operation
      of healthcare system within which they can effect change. It is important to
      identify and model the resource exchanges to ensure that the quality and safety
      of care are enhanced, efficiencies are increased and the overall healthcare
      service system is improved. We have shown that dynamic models allow us to study
      the exchange of resources. These are often intertwined within a socio-technical
      context in an informal manner and not accounted for in static models, yet capture
      a truer insight on the operations of a Careflow Network.

PMID- 28438103
TI  - Information and communication technology and the future of healthcare: Results of
      a multi-scenario Delphi survey.
AB  - Technological advances toward consumer-specific expectations require a sustained
      commitment and coordination across policy- and decision-makers. The present
      scenario-based study aimed at identifying prevailing perceptions regarding
      telehealth applications among Austrian healthcare experts. During a two-round
      online Delphi survey, panelists rated perceived benefits, obstacles,
      innovativeness, desirability, and estimated implementation date of 10 telehealth
      scenarios. Panelists (n = 73, 74% males) perceived that the implementation of
      telehealth scenarios could especially improve patients' knowledge, quality of
      social healthcare, and living standard. In contrast, the three top-ranked
      obstacles were costs, technical prerequisites, and data security. Survey
      participants rated innovativeness of the presented future scenarios as quite
      high, whereas perceived desirability was moderate. Overall, ratings suggested
      precautious attitudes toward technological innovations. The survey findings
      suggest building taskforces and enhancing communication between healthcare
      stakeholders to proactively shape the future of telehealth in Austria.

PMID- 28438104
TI  - Impact of a scribe program on patient throughput, physician productivity, and
      patient satisfaction in a community-based emergency department.
AB  - Previous literature on the impact of scribe programs varies and has mostly been
      reported from academic institutions or other clinics. We report the
      implementation of the scribe program in the emergency room of a community
      hospital and its impact on patient throughput, physician productivity, and
      patient satisfaction. We performed a quasi-experimental, before-and-after study
      measuring patient throughput metrics, physician productivity, and patient
      satisfaction. The intervention measuring the scribe implementation was divided
      into pre- and post-implementation periods. Patient throughput metrics were (1)
      door-to-room time, (2) room-to-doc time, (3) door-to-doc time, (4) doc-to
      disposition time, and (5) length of stay for discharged/admitted patients. Our
      secondary outcome was physician productivity, which was calculated by measuring
      total patients seen per hour and work relative value units per hour.
      Additionally, we calculated the time-motion analysis in minutes to measure the
      emergency department physician's efficiency by recording the following: (1) chart
      preparation, (2) chart review, (3) doctor-patient interaction, (4) physical
      examination, and (5) post-visit documentation. Finally, we measured patient
      satisfaction as provided by Press Ganey surveys. Data analysis was conducted in
      12,721 patient encounters in the pre-scribe cohort, and 13,598 patient encounters
      in the post-scribe cohort. All the patient throughput metrics were statistically
      significant (p < 0.0001). The patients per hour increased from 2.3 +/- 0.3 pre
      scribe to 3.2 +/- 0.6 post-scribe cohorts (p < 0.001). Total work relative value
      units per hour increased from 241(3.1 +/- 1.5 per hour) pre-scribe cohort to 336
      (5.2 +/- 1.4 per hour) post-scribe cohort (p < 0.001). The pre-scribe patient
      satisfaction was high and remained high in the post-scribe cohort. There was a
      significant increase in the clinician providing satisfactory feedback from the
      pre-scribe (3.9 +/- 0.3) to the post-scribe (4.7 +/- 0.1) cohorts (p < 0.01). We
      describe a prospective trial of medical scribe use in the emergency department
      setting to improve patient throughput, physician productivity, and patient
      satisfaction. We illustrate that scribe use in community emergency department is
      feasible and results in improvement in all three metrics.

PMID- 28438105
TI  - Design, functionality, and validity of the SWInCaRe, a web-based application used
      to administer cancer registry records.
AB  - We described the design of a web-based application (the Software Integrated
      Cancer Registry-SWInCaRe) used to administer data in a cancer registry and tested
      its validity and usability. A sample of 11,680 records was considered to compare
      the manual and automatic procedures. Sensibility and specificity, the Health IT
      Usability Evaluation Scale, and a cost-efficiency analysis were tested. Several
      data sources were used to build data packages through text-mining and record
      linkage algorithms. The automatic procedure showed small yet measurable
      improvements in both data linkage process and cancer cases estimation. Users
      perceived the application as useful to improve the time of coding and difficulty
      of the process: both time and cost-analysis were in favor of the automatic
      procedure. The web-based application resulted in a useful tool for the cancer
      registry, but some improvements are necessary to overcome limitations observed
      and to further automatize the process.

PMID- 28438106
TI  - Interprofessional education and social interaction: The use of automated external
      defibrillators in team-based basic life support.
AB  - Automated external defibrillators are pervasive computing devices designed for
      the treatment and management of acute sudden cardiac arrest. This study aims to
      explain users' actual use behavior in teams formed by different professions taken
      after a short time span of interaction with automated external defibrillator.
      Before the intervention, all the participants were certified with the American
      Heart Association Basic Life Support for healthcare providers. A statistically
      significant difference was revealed in mean individual automated external
      defibrillator technical skills between uniprofessional and interprofessional
      groups. The technical automated external defibrillator team scores were greater
      for groups with interprofessional than for those with uniprofessional education.
      The nontechnical automated external defibrillator skills of interprofessional and
      uniprofessional teams revealed differences in advantage of interprofessional
      teams. Students positively accept automated external defibrillators if well
      defined and validated training opportunities to use them expertly are available.
      Uniprofessional teams were successfully supported by their members and, thereby,
      used automated external defibrillator effectively. Furthermore, the
      interprofessional approach resulted in as much effective teamwork as the
      uniprofessional approach.

PMID- 28438107
TI  - Accessing care summaries at point-of-care:Implementation of mobile devices for
      personal carers in aged care.
AB  - Continued development of mobile technology now allows access to information at
      the point-of-care. This study was conducted to evaluate the use of one such tool
      on a mobile device, from the carer perspective. Caregivers across 12 aged-care
      facilities were supplied mobile devices to access a Picture Care Plan (PCP), a
      specific tool designed around the role of the personal carer. An anonymous
      questionnaire was subsequently completed by 85 carers with questions relating to
      participants' experience. Perceived helpfulness of the PCP at the point-of-care
      was high (87%). A significant number of participants believed the use of the PCP
      increased resident safety and quality of care (76%). Practical components related
      to the carrying of the device, network speed and the requirement to maintain
      communication with senior members of staff to ascertain updates were also
      expressed by participants. Findings suggest that staff are receptive to adoption
      of mobile devices to access care directives at the point-of-care and that the
      technology is useful.

PMID- 28438108
TI  - 17-AAG and Apoptosis, Autophagy, and Mitophagy in Canine Osteosarcoma Cell Lines.
AB  - Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying
      the mechanisms of tumor cell resistance to treatments is an urgent need. We
      tested the geldanamycin derivative 17-AAG (17-allylamino-17
      demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2
      canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic
      tumors, respectively. With the aim to understand the interplay between cell
      death, autophagy, and mitophagy, in light of the dual effect of autophagy in
      regulating cancer cell viability and death, D22 and D17 cells were treated with
      different concentrations of 17-AAG (0.5 MUM, 1 MUM) for 24 and 48 hours. 17-AAG
      induced apoptosis, necrosis, autophagy, and mitophagy were assessed by
      transmission electron microscopy, flow cytometry, and immunofluorescence. A
      simultaneous increase in apoptosis, autophagy, and mitophagy was observed only in
      the D22 cell line, while D17 cells showed low levels of apoptotic cell death.
      These results reveal differential cell response to drug-induced stress depending
      on tumor cell type. Therefore, pharmacological treatments based on proapoptotic
      chemotherapy in association with autophagy regulators would benefit from a
      predictive in vitro screening of the target cell type.

PMID- 28438109
TI  - Practical Stereology Applications for the Pathologist.
AB  - Qualitative histopathology is the gold standard for routine examination of
      morphological tissue changes in the regulatory or academic environment. The human
      eye is exceptional for pattern recognition but often cannot detect small changes
      in quantity. In cases where detection of subtle quantitative changes is critical,
      more sensitive methods are required. Two-dimensional histomorphometry can provide
      additional quantitative information and is quite useful in many cases. However,
      the provided data may not be referent to the entire tissue and, as such, it makes
      several assumptions, which are sources of bias. In contrast, stereology is design
      based rather than assumption based and uses stringent sampling methods to obtain
      accurate and precise 3-dimensional information using geometrical and statistical
      principles. Recent advances in technology have made stereology more approachable
      and practical for the pathologist in both regulatory and academic environments.
      This review introduces pathologists to the basic principles of stereology and
      walks the reader through some real-world examples for the application of these
      principles in the workplace.

PMID- 28438110
TI  - Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus.
AB  - Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic
      fever that annually infects an estimated 100 000 to 300 000 persons in West
      Africa. This pathogenesis study evaluated the temporal progression of disease in
      guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain
      of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for
      Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67)
      were serially sampled to evaluate the temporal progression of infection, gross
      and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs
      developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing
      by day 7 to 8 PE. Complete blood counts revealed lymphopenia and
      thrombocytopenia. Gross pathologic findings included skin lesions and congested
      lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7
      PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered
      hepatocellular degeneration and cell death were also noted in the liver and, to a
      lesser extent, in other tissues including the haired skin, lung, heart, adrenal
      gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate
      staining for viral antigen were fibroblastic reticular cells and
      macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study
      demonstrates similarities between Lassa viral disease in human infections and
      experimental guinea pig infection. These shared pathologic characteristics
      support the utility of guinea pigs as an additional animal model for vaccine and
      therapeutic development under the Food and Drug Administration's Animal Rule.

PMID- 28438111
TI  - Pathology of Naturally Occurring Bacillary Hemoglobinuria in Cattle.
AB  - Clostridium haemolyticum causes bacillary hemoglobinuria (BH), an infectious and
      usually fatal disease that occurs mostly in cattle, which is clinically
      characterized by jaundice, hemoglobinuria, and anemia. The trematode Fasciola
      hepatica has been commonly reported as the main predisposing factor that triggers
      this condition. The authors evaluated 20 naturally occurring cases of bovine BH
      to characterize the pathology and pathogenesis of the disease. Grossly, the most
      consistent finding was a large, frequently single focus of necrosis surrounded by
      a red to purple halo, observed most frequently on the parietal surface of the
      right and left hepatic lobes. Other findings were jaundice, dark-brown
      discoloration of kidneys, and red urine in the urinary bladder. Microscopically,
      characteristic lesions were locally extensive, necrotizing hepatitis with
      thrombosis and numerous intralesional Gram-positive rod-shaped bacteria, and
      acute renal tubular necrosis. By immunohistochemistry, many hepatocytes outside
      the necrotic focus in the liver were positive for activated caspase 3, suggesting
      that those cells were undergoing apoptosis. Ultrastructural evaluation revealed
      hepatocyte necrosis, hemolysis, and clumps of vegetative and sporulating bacilli
      within the liver. Polymerase chain reaction for the C. haemolyticum beta toxin
      gene was positive in randomly selected liver samples. No gross or microscopic
      lesions indicative of fascioliasis were detected in the liver of any animal,
      suggesting that other yet undetermined predisposing factors were associated with
      these cases of BH.

PMID- 28438112
TI  - H3N2 Canine Influenza Virus Infection in a Dog.
AB  - In 2015, H3N2 canine influenza emerged in dogs in the greater Chicago area.
      During this time, a 10-year-old German Shepherd dog presented to the referring
      veterinarian with lethargy and coughing that quickly progressed to death. This
      report describes the macroscopic and microscopic lesions and the molecular
      testing performed to identify the novel North American H3N2 strain of canine
      influenza. The larynx, pharynx, and trachea were covered by a fibrinonecrotic
      membrane. Bilaterally, the lungs had multifocal subpleural necrosis of the caudal
      lung lobes with hemorrhage, congestion, and pulmonary edema. Staphylococcus
      pseudointermedius was isolated from the lung. Mycoplasma cynos was identified by
      real-time polymerase chain reaction from nasal passages, oropharynx, larynx,
      trachea, and cranial lung lobes. The neuraminidase gene sequence from the
      influenza virus isolated obtained from this dog had >=98% homology to the strain
      circulating in the Chicago area.

PMID- 28438113
TI  - Hopping Over Red Leg: The Metamorphosis of Amphibian Pathology.

PMID- 28438114
TI  - Small Ruminant Lentiviruses: Strain Variation, Viral Tropism, and Host Genetics
      Influence Pathogenesis.

PMID- 28438115
TI  - An auditory display tool for DNA sequence analysis.
AB  - BACKGROUND: DNA Sonification refers to the use of an auditory display to convey
      the information content of DNA sequence data. Six sonification algorithms are
      presented that each produce an auditory display. These algorithms are logically
      designed from the simple through to the more complex. Three of these parse
      individual nucleotides, nucleotide pairs or codons into musical notes to give
      rise to 4, 16 or 64 notes, respectively. Codons may also be parsed degenerately
      into 20 notes with respect to the genetic code. Lastly nucleotide pairs can be
      parsed as two separate frames or codons can be parsed as three reading frames
      giving rise to multiple streams of audio. RESULTS: The most informative
      sonification algorithm reads the DNA sequence as codons in three reading frames
      to produce three concurrent streams of audio in an auditory display. This
      approach is advantageous since start and stop codons in either frame have a
      direct affect to start or stop the audio in that frame, leaving the other frames
      unaffected. Using these methods, DNA sequences such as open reading frames or
      repetitive DNA sequences can be distinguished from one another. These
      sonification tools are available through a webpage interface in which an input
      DNA sequence can be processed in real time to produce an auditory display
      playable directly within the browser. The potential of this approach as an
      analytical tool is discussed with reference to auditory displays derived from
      test sequences including simple nucleotide sequences, repetitive DNA sequences
      and coding or non-coding genes. CONCLUSION: This study presents a proof-of
      concept that some properties of a DNA sequence can be identified through
      sonification alone and argues for their inclusion within the toolkit of DNA
      sequence browsers as an adjunct to existing visual and analytical tools.

PMID- 28438116
TI  - The predictive nature of transcript expression levels on protein expression in
      adult human brain.
AB  - BACKGROUND: Next generation sequencing methods are the gold standard for
      evaluating expression of the transcriptome. When determining the biological
      implications of such studies, the assumption is often made that transcript
      expression levels correspond to protein levels in a meaningful way. However, the
      strength of the overall correlation between transcript and protein expression is
      inconsistent, particularly in brain samples. RESULTS: Following high-throughput
      transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem
      mass spectrometry) analyses of adult human brain samples, we compared the
      correlation in the expression of transcripts and proteins that support various
      biological processes, molecular functions, and that are located in different
      areas of the cell. Although most categories of transcripts have extremely weak
      predictive value for the expression of their associated proteins (R2 values of <
      10%), transcripts coding for protein kinases and membrane-associated proteins,
      including those that are part of receptors or ion transporters, are among those
      that are most predictive of downstream protein expression levels. CONCLUSIONS:
      The predictive value of transcript expression for corresponding proteins is
      variable in human brain samples, reflecting the complex regulation of protein
      expression. However, we found that transcriptomic analyses are appropriate for
      assessing the expression levels of certain classes of proteins, including those
      that modify proteins, such as kinases and phosphatases, regulate metabolic and
      synaptic activity, or are associated with a cellular membrane. These findings can
      be used to guide the interpretation of gene expression results from primate brain
      samples.

PMID- 28438117
TI  - Reproducibility of African giant pouched rats detecting Mycobacterium
      tuberculosis.
AB  - BACKGROUND: African pouched rats sniffing sputum samples provided by local
      clinics have significantly increased tuberculosis case findings in Tanzania and
      Mozambique. The objective of this study was to determine the reproducibility of
      rat results. METHODS: Over an 18-month period 11,869 samples were examined by the
      rats. Intra-rater reliability was assessed through Yule's Q. Inter-rater
      reliability was assessed with Krippendorff's alpha. RESULTS: Intra-rater
      reliability was high, with a mean Yule's Q of 0.9. Inter-rater agreement was
      fair, with Krippendorf's alpha ranging from 0.15 to 0.45. Both Intra- and Inter
      rater reliability was independent of the sex of the animals, but they were
      positively correlated with age. Both intra- and inter-rater agreement was lowest
      for samples designated as smear-negative by the clinics. CONCLUSION: Overall, the
      reproducibility of tuberculosis detection rat results was fair and diagnostic
      results were therefore independent of the rats used.

PMID- 28438118
TI  - Predictors of delayed culture conversion among Ugandan patients.
AB  - BACKGROUND: Estimates of month-2 culture conversion, a proxy indicator of
      tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type
      and geographically with lower rates reported among African sites. The sub-study
      aimed at comparing TB detection rates of different culture media, within and
      across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment
      follow-up period, and to establish predictors of month-2 culture non-conversion
      among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda. METHODS:
      Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen
      (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months
      for treatment monitoring. Conversion rates were compared at month-2, 4 and 6
      across cultures and treatment-type. Binomial regression analysis performed for
      predictors of month-2 non-conversion. RESULTS: Of the 100 enrolled patients, 45%
      had converted based on combined LJ and MGIT by month-2, with no significant
      differences across treatment arms, p = 0.721. LJ exhibited higher conversion
      rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs
      88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms.
      All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and
      social service jobs independently predict month-2 non-conversion. CONCLUSION: The
      month-2 culture conversion used in phase 2 clinical trials as surrogate marker of
      treatment efficacy is influenced by the culture method used for monitoring
      mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic
      trials using early efficacy endpoint should use the same culture method across
      sites. The Time-to-detection of MTB on MGIT prior to treatment and working in
      Social service jobs bear an increased risk of culture non-conversion at month-2.
      TRIAL REGISTRATION: ISRCTN ISRCTN55670677 . Registered 09th November 2010.
      Retrospectively registered.

PMID- 28438119
TI  - DFI-seq identification of environment-specific gene expression in uropathogenic
      Escherichia coli.
AB  - BACKGROUND: During infection of the urinary tract, uropathogenic Escherichia coli
      (UPEC) are exposed to different environments, such as human urine and the
      intracellular environments of bladder epithelial cells. Each environment elicits
      a distinct bacterial environment-specific transcriptional response. We combined
      differential fluorescence induction (DFI) with next-generation sequencing,
      collectively termed DFI-seq, to identify differentially expressed genes in UPEC
      strain UTI89 during growth in human urine and bladder cells. RESULTS: DFI-seq
      eliminates the need for iterative cell sorting of the bacterial library and
      yields a genome-wide view of gene expression. By analysing the gene expression of
      UPEC in human urine we found that genes involved in amino acid biosynthesis were
      upregulated. Deletion mutants lacking genes involved in arginine biosynthesis
      were outcompeted by the wild type during growth in human urine and inhibited in
      their ability to invade or proliferate in the J82 bladder epithelial cell line.
      Furthermore, DFI-seq was used to identify genes involved in invasion of J82
      bladder epithelial cells. 56 genes were identified to be differentially expressed
      of which almost 60% encoded hypothetical proteins. One such gene UTI89_C5139,
      displayed increased adhesion and invasion of J82 cells when deleted from UPEC
      strain UTI89. CONCLUSIONS: We demonstrate the usefulness of DFI-seq for
      identification of genes required for optimal growth of UPEC in human urine, as
      well as potential virulence genes upregulated during infection of bladder cell
      culture. DFI-seq holds potential for the study of bacterial gene expression in
      live-animal infection systems. By linking fitness genes, such as those genes
      involved in amino acid biosynthesis, to virulence, this study contributes to our
      understanding of UPEC pathophysiology.

PMID- 28438120
TI  - Transcriptomic analysis links gene expression to unilateral pollen-pistil
      reproductive barriers.
AB  - BACKGROUND: Unilateral incompatibility (UI) is an asymmetric reproductive barrier
      that unidirectionally prevents gene flow between species and/or populations. UI
      is characterized by a compatible interaction between partners in one direction,
      but in the reciprocal cross fertilization fails, generally due to pollen tube
      rejection by the pistil. Although UI has long been observed in crosses between
      different species, the underlying molecular mechanisms are only beginning to be
      characterized. The wild tomato relative Solanum habrochaites provides a unique
      study system to investigate the molecular basis of this reproductive barrier, as
      populations within the species exhibit both interspecific and interpopulation UI.
      Here we utilized a transcriptomic approach to identify genes in both pollen and
      pistil tissues that may be key players in UI. RESULTS: We confirmed UI at the
      pollen-pistil level between a self-incompatible population and a self-compatible
      population of S. habrochaites. A comparison of gene expression between pollinated
      styles exhibiting the incompatibility response and unpollinated controls revealed
      only a small number of differentially expressed transcripts. Many more
      differences in transcript profiles were identified between UI-competent versus UI
      compromised reproductive tissues. A number of intriguing candidate genes were
      highly differentially expressed, including a putative pollen arabinogalactan
      protein, a stylar Kunitz family protease inhibitor, and a stylar peptide hormone
      Rapid ALkalinization Factor. Our data also provide transcriptomic evidence that
      fundamental processes including reactive oxygen species (ROS) signaling are
      likely key in UI pollen-pistil interactions between both populations and species.
      CONCLUSIONS: Gene expression analysis of reproductive tissues allowed us to
      better understand the molecular basis of interpopulation incompatibility at the
      level of pollen-pistil interactions. Our transcriptomic analysis highlighted
      specific genes, including those in ROS signaling pathways that warrant further
      study in investigations of UI. To our knowledge, this is the first report to
      identify candidate genes involved in unilateral barriers between populations
      within a species.

PMID- 28438121
TI  - Leg elevation decreases the incidence of post-spinal hypotension in cesarean
      section: a randomized controlled trial.
AB  - BACKGROUND: Maternal hypotension is a common complication after spinal anesthesia
      for cesarean section (CS). In this study we investigated the role of leg
      elevation (LE) as a method for prevention of post-spinal hypotension (PSH) for
      cesarean section. METHODS: One hundred and fifty full term parturients scheduled
      for CS were included in the study. Patients were randomized into two groups:
      Group LE (leg elevation group, n = 75) and group C (Control group, n = 75).
      Spinal block was performed in sitting position after administration of 10 mL/Kg
      Ringer's lactate as fluid preload. After successful intrathecal injection of
      local anesthetic, Patients were positioned in the supine position. Leg elevation
      was performed for LE group directly after spinal anesthesia and maintained till
      skin incision. Intraoperative hemodynamic parameters (Arterial blood pressure and
      heart rate), intra-operative ephedrine consumption, incidence of PSH, and
      incidence of nausea and vomiting were reported. RESULTS: LE group showed lower
      incidence of PSH (34.7% Vs 58.7%, P = 0.005) compared to the control group.
      Arterial blood pressure was higher in the LE group compared to the control group
      in the first two readings after spinal block. Other readings showed comparable
      arterial blood pressure and heart rate values between both study groups; however,
      LE showed less ephedrine consumption (4.9 +/- 7.8 mg Vs 10 +/- 11 mg, P = 0.001).
      CONCLUSION: LE performed immediately after spinal block reduced the incidence of
      PSH in parturients undergoing CS. TRIAL REGISTRATION: The study was registered at
      Pan African Clinical Trials Registry system on 5/10/2015 with trial number
      PACTR201510001295348 .

PMID- 28438122
TI  - Comprehensive performance comparison of high-resolution array platforms for
      genome-wide Copy Number Variation (CNV) analysis in humans.
AB  - BACKGROUND: High-resolution microarray technology is routinely used in basic
      research and clinical practice to efficiently detect copy number variants (CNVs)
      across the entire human genome. A new generation of arrays combining high probe
      densities with optimized designs will comprise essential tools for genome
      analysis in the coming years. We systematically compared the genome-wide CNV
      detection power of all 17 available array designs from the Affymetrix, Agilent,
      and Illumina platforms by hybridizing the well-characterized genome of 1000
      Genomes Project subject NA12878 to all arrays, and performing data analysis using
      both manufacturer-recommended and platform-independent software. We benchmarked
      the resulting CNV call sets from each array using a gold standard set of CNVs for
      this genome derived from 1000 Genomes Project whole genome sequencing data.
      RESULTS: The arrays tested comprise both SNP and aCGH platforms with varying
      designs and contain between ~0.5 to ~4.6 million probes. Across the arrays CNV
      detection varied widely in number of CNV calls (4-489), CNV size range (~40 bp to
      ~8 Mbp), and percentage of non-validated CNVs (0-86%). We discovered strikingly
      strong effects of specific array design principles on performance. For example,
      some SNP array designs with the largest numbers of probes and extensive exonic
      coverage produced a considerable number of CNV calls that could not be validated,
      compared to designs with probe numbers that are sometimes an order of magnitude
      smaller. This effect was only partially ameliorated using different analysis
      software and optimizing data analysis parameters. CONCLUSIONS: High-resolution
      microarrays will continue to be used as reliable, cost- and time-efficient tools
      for CNV analysis. However, different applications tolerate different limitations
      in CNV detection. Our study quantified how these arrays differ in total number
      and size range of detected CNVs as well as sensitivity, and determined how each
      array balances these attributes. This analysis will inform appropriate array
      selection for future CNV studies, and allow better assessment of the CNV
      analytical power of both published and ongoing array-based genomics studies.
      Furthermore, our findings emphasize the importance of concurrent use of multiple
      analysis algorithms and independent experimental validation in array-based CNV
      detection studies.

PMID- 28438123
TI  - Small RNA sequencing reveals a role for sugarcane miRNAs and their targets in
      response to Sporisorium scitamineum infection.
AB  - BACKGROUND: Sugarcane smut caused by Sporisorium scitamineum leads to a
      significant reduction in cane yield and sucrose content. MicroRNAs (miRNAs) play
      an important role in regulating plant responses to biotic stress. The present
      study was the first to use two sugarcane genotypes, YA05-179 (smut-resistant) and
      ROC22 (smut-susceptible), to identify differentially expressed miRNAs in
      sugarcane challenged with S. scitamineum by using high-throughput sequencing.
      RESULTS: The predicted target gene number corresponding to known differentially
      expressed miRNAs in YA05-179 was less than that in ROC22, however most of them
      were in common. Expression of differential miRNAs under S. scitamineum challenge
      was mostly downregulated, with similar trends in the two varieties. Gene ontology
      (GO) analysis showed that the target gene classification of known miRNAs was
      similar to that of the newly identified miRNAs. These were mainly associated with
      cellular processes and metabolic processes in the biological process category, as
      well as combination and catalytic activity in the molecular function category.
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis
      revealed that these predicted target genes involved in a series of physiological
      and biochemical pathways or disease resistance-related physiological metabolism
      and signal transduction pathways, suggesting that the molecular interaction
      mechanism between sugarcane and S. scitamineum was a complex network system.
      These findings also showed certain predicted target genes of miR5671, miR5054,
      miR5783, miR5221, and miR6478 play roles in the mitogen-activated protein kinase
      (MAPK) signaling pathway, plant hormone signal transduction, and plant-pathogen
      interaction. Quantitative real-time PCR (qRT-PCR) analysis showed that majority
      of the known miRNAs and its predicted target genes followed a negatively
      regulated mode. Seven out of eight predicted target genes showed identical
      expression after 12 h treatment and reached the highest degree of matching at 48
      h, indicating that the regulatory role of miRNAs on the target genes in sugarcane
      was maximized at 48 h after S. scitamineum challenge. CONCLUSIONS: Taken
      together, our findings serve as evidence for the association of miRNA expression
      with the molecular mechanism underlying the pathogenesis of sugarcane smut,
      particularly on the significance of miRNA levels in relation to the cultivation
      of smut-resistant sugarcane varieties.

PMID- 28438124
TI  - Effectiveness of an individual, online e-learning program about sexually
      transmitted infections: a prospective cohort study.
AB  - BACKGROUND: Primary health-care professionals play an important role in the
      treatment and prevention of Sexually Transmitted Infections (STI). Continuing
      Medical Education (CME)-courses can influence the knowledge and behavior of
      health-care professionals concerning STI. We performed a prospective cohort study
      to evaluate if the individual and online e-learning program "The STI
      consultation", which uses the Commitment-to-Change (CtC)-method, is able to
      improve the knowledge, attitude and behavior of Dutch General Practitioners
      (GPs), concerning the STI-consultation. This e-learning program is an individual,
      accredited, online CME-program, which is freely available for all GPs and GP
      trainees in the Netherlands. METHODS: In total 2192 participants completed the
      questionnaire before completing the e-learning program and 249 participants
      completed the follow-up questionnaire after completing the e-learning program.
      The effect of the program on their knowledge, attitude and behavior concerning
      the STI-consultation was evaluated. RESULTS: In total 193 participants formulated
      601 learning points that matched the learning objectives of the program. The
      knowledge and attitude of the participants improved, which persisted up to two
      years after completing the program. Another 179 participants formulated a total
      of 261 intended changes concerning the sexual history taking, additional
      investigation and treatment of STI, 97.2% of these changes was partially or fully
      implemented in daily practice. Also, 114 participants formulated a total of 180
      "unintended" changes in daily practice. These changes concerned the attitude of
      participants towards STI and the working conditions concerning the STI
      consultation. CONCLUSION: The individual, online e-learning program "The STI
      consultation", which uses the CtC-method, has a small but lasting, positive
      effect on the knowledge, attitude, and behavior of GPs concerning the STI
      consultation.

PMID- 28438126
TI  - Prevalence of and Factors Associated with Myopia in Inner Mongolia Medical
      Students in China, a cross-sectional study.
AB  - BACKGROUND: To further explore characteristics of myopia and changes in factors
      associated with myopia among students at Inner Mongolia Medical University.
      METHODS: Two cross-sectional censuses were conducted in 2011 and 2013.
      Participants were medical students residing on campus in 2011 and 2013. Logistic
      regression analysis was performed to ascertain associations with basic
      information, genetic factors, environmental factors. The chi2 test was used to
      test for differences in prevalence between 2011 and 2013. Prevalence was
      calculated at various myopia occurrence times among different parental myopia
      statuses. RESULTS: A total of 11,138 students enrolled from 2007 to 2012
      completed the questionnaire. The prevalence of myopia in 2011 and 2013 was 70.50%
      and 69.21%, respectively, no statistically significant difference existed between
      the two censuses (p = 0.12). Both censuses were completed by 1015 students. There
      were no differences among the various year of study in 2011 or 2013. Myopic
      prevalence increased with an increased number of myopic parents: the prevalence
      if both parents were myopic was over 90%, nearly 80% if one parent was myopic,
      and less than 70% with non-myopic parents (p < 0.001). Myopic occurrence ranked
      from earliest to latest was in kindergarten and primary school when both parents
      were myopic, in middle school when one parent was myopic, and in university when
      no parent was myopic. Students staying up late, using a computer more than 3 h
      per day, not performing eye exercises, using eye drops, and rubbing the eyes at
      high risk for myopia. CONCLUSIONS: Myopic status was stable during the university
      period. Genetic factors play a major role in myopia. Protective measures are
      useful for university students.

PMID- 28438125
TI  - Chlamydia spp. development is differentially altered by treatment with the LpxC
      inhibitor LPC-011.
AB  - BACKGROUND: Chlamydia species are obligate intracellular bacteria that infect a
      broad range of mammalian hosts. Members of related genera are pathogens of a
      variety of vertebrate and invertebrate species. Despite the diversity of
      Chlamydia, all species contain an outer membrane lipooligosaccharide (LOS) that
      is comprised of a genus-conserved, and genus-defining, trisaccharide 3-deoxy-D
      manno-oct-2-ulosonic acid Kdo region. Recent studies with lipopolysaccharide
      inhibitors demonstrate that LOS is important for the C. trachomatis developmental
      cycle during RB- > EB differentiation. Here, we explore the effects of one of
      these inhibitors, LPC-011, on the developmental cycle of five chlamydial species.
      RESULTS: Sensitivity to the drug varied in some of the species and was conserved
      between others. We observed that inhibition of LOS biosynthesis in some
      chlamydial species induced formation of aberrant reticulate bodies, while in
      other species, no change was observed to the reticulate body. However, loss of
      LOS production prevented completion of the chlamydial reproductive cycle in all
      species tested. In previous studies we found that C. trachomatis and C. caviae
      infection enhances MHC class I antigen presentation of a model self-peptide. We
      find that treatment with LPC-011 prevents enhanced host-peptide presentation
      induced by infection with all chlamydial-species tested. CONCLUSIONS: The data
      demonstrate that LOS synthesis is necessary for production of infectious progeny
      and inhibition of LOS synthesis induces aberrancy in certain chlamydial species,
      which has important implications for the use of LOS synthesis inhibitors as
      potential antibiotics.

PMID- 28438127
TI  - Lessons learned by surveillance during the tail-end of the Ebola outbreak in
      Guinea, June-October 2015: a case series.
AB  - BACKGROUND: By the end of the 2013-2016 West African Ebola Virus Disease (EVD)
      outbreaks, a total of 3814 cases(probable and confirmed) and 2544 deaths were
      reported in Guinea. Clearly, surveillance activities aiming at stopping human-to
      human transmission have been the breakthrough of EVD outbreak management, but
      their application has been at times easier said than done. This article presents
      five confirmed or probable EVD cases that arose in Conakry towards the end of the
      Guinea epidemic, which demonstrate flaws in surveillance and follow-up. CASE
      PRESENTATION: For case 1, safe burial requirements were not followed. For cases 1
      and 2, negative PolymeraseChain Reaction (PCR) results were interpreted as no
      infection. For the first case, the sample may have not been taken properly while
      for the second the disease was possibly at its early stage. Case 3 was stopped at
      a border health checkpoint and despite her high temperature she was allowed to
      continue the bus journey. For case 4, an oral swab sample was supposedly taken
      after death but could not be found for retrospective testing. Despite
      characteristic symptomatology, case 5 was not identified as a suspect case for as
      long as 3 weeks. CONCLUSION: In epidemic contexts, health systems must be able to
      track all samples of suspect cases and deaths,regardless of their laboratory
      results. Social mobilization in communities and training in health care
      facilities must be strengthened at the tail of an outbreak, to avoid the natural
      slackening of disease surveillance, in particular for long-lasting and deadly
      epidemics.

PMID- 28438129
TI  - Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a
      paradoxical manifestation associated with deficiency of antigen-specific
      regulatory T-cells?
AB  - BACKGROUND: Due to its chronic subclinical course and large spectrum of
      manifestations, leprosy often represents a diagnostic challenge. Even with proper
      anti-mycobacteria treatment, leprosy follow up remains challenging: almost half
      of leprosy patients may develop reaction episodes. Leprosy is an infrequent
      complication of solid organ transplant recipients. This case report illustrates
      the challenges in diagnosing and managing leprosy and its reactional states in a
      transplant recipient. CASE PRESENTATION: A 53-year-old man presented 34 months
      after a successful renal transplantation a borderline-tuberculoid leprosy with
      signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were
      atypical, and diagnosis was only made when granulomatous neuritis was found in a
      cutaneous biopsy. He was successfully treated with the WHO recommended multidrug
      therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe
      T1R immediately after completion of the MDT but no signs of allograft rejection.
      T1R results from flare-ups of the host T-helper-1 cell-mediated immune response
      against Mycobacterium leprae antigens in patients with immunologically unstable,
      borderline forms of leprosy and has been considered an inflammatory syndrome in
      many aspects similar to the immune reconstitution inflammatory syndromes (IRS).
      The T1R was successfully treated by increasing the prednisone dose without
      modifying the other immunosuppressive drugs used for preventing allograft
      rejection. Immunological study revealed that the patient had a profound depletion
      of both in situ and circulating regulatory T-cells and lack of expansion of the
      Tregs upon M. leprae stimulation compared to T1R leprosy patients without
      iatrogenic immunosuppression. CONCLUSIONS: Our case report highlights that
      leprosy, especially in the transplant setting, requires a high degree of clinical
      suspicion and the contribution of histopathology. It also suggests that the
      development of upgrading inflammatory syndromes such as T1R can occur despite the
      sustained immunosuppressors regimen for preventing graft rejection. Our
      hypothesis is that the well-known deleterious effects of these immunosuppressors
      on pathogen-induced regulatory T-cells contributed to the immunedysregulation and
      development T1R.

PMID- 28438128
TI  - Viral aetiologies of acute encephalitis in a hospital-based South Asian
      population.
AB  - BACKGROUND: The aetiological spectrum of acute encephalitis shows inter- and
      intra-geographical variations. We aimed to identify the viruses that cause
      infectious encephalitis in Sri Lanka, which represents a South Asian population.
      METHODS: A cross-sectional study was conducted among 99 patients with
      encephalitis/meningoencephalitis admitted to two tertiary-care hospitals in
      Colombo. Cerebrospinal fluid and serum were tested for conventional and emerging
      encephalitogenic viruses. Specific nucleic acid amplification and antibody assays
      were used to identify viruses. Plaque reduction neutralization test was done to
      confirm the diagnosis of West Nile virus (WNV). RESULTS: Patients' age ranged
      from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male:female ratio of
      1.75:1. A viral aetiology was identified in only 27.3%. These included dengue
      virus (40.7%), Japanese encephalitis virus (25.9%), varicella zoster virus, WNV
      and probable Epstein Barr virus (11.1% each). None were positive for herpes
      simplex viruses or cytomegalovirus. Screening for bacterial aetiologies was
      negative for all patients. There were no distinguishable clinical or laboratory
      findings between the different viral aetiologies. The case fatality rate was 7%,
      which was higher among patients with an identified viral aetiology. CONCLUSIONS:
      A viral aetiology was identified in only about a quarter of patients with
      encephalitis. Dengue virus accounted for the majority.

PMID- 28438130
TI  - The safety and efficacy of percutaneous intraductal radiofrequency ablation in
      unresectable malignant biliary obstruction: A single-institution experience.
AB  - BACKGROUND: Patients with unresectable malignant biliary obstruction have limited
      life expectancy because of limited stent patency and tumor progression. The aim
      of our study was to retrospectively evaluate the safety and efficacy of combining
      intraductal RFA with biliary metal stent placement for patients with malignant
      biliary obstruction. METHODS: Patients who received percutaneous intraductal RFA
      and biliary stent placement for malignant biliary obstruction between 2013 and
      2015 were identified. Outcomes were stent patency, technique and clinical success
      rate, overall survival (OS) and complication rates. Kaplan-Meier and Cox
      regression analyses were used to examine the association of various factors with
      stent patency and OS. Complications and laboratory abnormalities were recorded.
      RESULTS: Fifty patients were treated with percutaneous RFA and stent placement.
      The rates of technical success and clinical success were 98% and 92%,
      respectively. The median stent patency was 7.0 (95% confidence interval [CI]:
      5.3, 8.7) months and OS was 5.0 (95% CI: 4.0, 6.0) months. On univariable
      analysis, previously cholangitis was an independent poor prognosis factor for
      recurrent biliary obstruction. OS was improved in patients who received more than
      one intervention compared to those who received only one intervention (log-rank P
      = 0.007), and in those treated without versus those treated with sequential
      chemotherapy (log-rank P = 0.017). On multivariable analysis, the occurrence of
      more than one intervention (P = 0.019) had independent prognostic significance
      for OS. CONCLUSION: Percutaneous RFA and stent placement is a technically safe
      and feasible therapeutic option for the palliative treatment of malignant biliary
      obstruction. The long-term efficacy and safety of the procedure is promising, but
      further study is required via randomized and prospective trials.

PMID- 28438131
TI  - Tablets at the bedside - iPad-based visual field test used in the diagnosis of
      Intrasellar Haemangiopericytoma: a case report.
AB  - BACKGROUND: In the assessment of a pituitary mass, objective visual field testing
      represents a valuable means of evaluating mass effect, and thus in deciding
      whether surgical management is warranted. CASE PRESENTATION: In this vignette, we
      describe a 73 year-old lady who presented with a three-week history of frontal
      headache, and 'blurriness' in the left side of her vision, due to a WHO grade III
      anaplastic haemangiopericytoma compressing the optic chiasm. We report how timely
      investigations, including an iPad-based visual field test (Melbourne Rapid Field,
      (MRF)) conducted at the bedside aided swift and appropriate management of the
      patient. CONCLUSIONS: We envisage such a test having a role in assessing bed
      bound patients in hospital where access to formal visual field testing is
      difficult, or indeed in rapid testing of visual fields at the bedside to screen
      for post-operative complications, such as haematoma.

PMID- 28438132
TI  - Early detection of multidrug- and pre-extensively drug-resistant tuberculosis
      from smear-positive sputum by direct sequencing.
AB  - BACKGROUND: Emergence of multidrug- and extensively drug-resistant tuberculosis
      (M/XDR-TB) is a major hurdle for TB control programs especially in developing
      countries like China. Resistance to fluoroquinolones is high among MDR-TB
      patients. Early diagnosis of MDR/pre-XDR-TB is essential for lowering
      transmission of drug-resistant TB and adjusting the treatment regimen. METHODS:
      Smear-positive sputum specimens (n = 186) were collected from Wuhan Institute for
      Tuberculosis Control. The DNA was extracted from the specimens and run through a
      Sanger sequencing assay to detect mutations associated with MDR/pre-XDR-TB
      including the rpoB core region for rifampicin (RIF) resistance; katG and inhA
      promoter for isoniazid (INH) resistance; and gyrA for fluoroquinolone (FQ)
      resistance. Sequencing data were compared to phenotypic Lowenstein-Jensen (L-J)
      proportion method drug susceptibility testing (DST) results for performance
      analysis. RESULTS: By comparing the mutation data with phenotypic results, the
      detection rates of MDR-TB and pre-XDR-TB were 84.31% (43/51) and 83.33% (20/24),
      respectively. The sequencing assay illustrated good sensitivity for the detection
      of resistance to RIF (96.92%), INH (86.89%), FQ (77.50%). The specificities of
      the assay were 98.35% for RIF, 99.20% for INH, and 97.26% for FQ. CONCLUSIONS:
      The sequencing assay is an efficient, accurate method for detection of MDR-TB and
      pre-XDR-TB from clinical smear-positive sputum specimens, should be considered as
      a supplemental method for obtaining early DST results before the availability of
      phenotypic DST results. This could be of benefit to early diagnosis, adjusting
      the treatment regimen and controlling transmission of drug-resistant TB.

PMID- 28438133
TI  - Evaluation of the enhanced meningitis surveillance system, Yendi municipality,
      northern Ghana, 2010-2015.
AB  - BACKGROUND: Meningitis is the inflammation of the meninges of the brain and or
      spinal cord. Global mortality rates vary from 2% to 30%. Epidemic meningitis
      remains a public health concern along the meningitis belt of Africa. Despite the
      operation of an enhanced meningitis surveillance system in Ghana, institutional
      mortality rates are estimated to range from 36% to 50%. In 2014, Yendi recorded
      83 confirmed cases; with focal epidemics in some sub-municipals. We evaluated the
      system over a five-year period to find out whether it was achieving its
      objectives of systematic collection and analyses of data for the prevention or
      early detection of meningitis epidemics. METHODS: We used cross-sectional design.
      Both qualitative and quantitative data from Yendi Municipality between January
      2010 and December 2015 were collected and analyzed. The updated guidelines for
      evaluating surveillance systems from Centers for Disease Control and Prevention
      were used. Content analysis was performed on the responses of key informants.
      Surveillance data was analyzed using MS-Excel. RESULTS: Fifteen healthcare
      workers were interviewed. For the period under evaluation, the annual incidence
      of meningitis ranged from 1.6/100,000 in 2012 to 62.6/100,000 in 2014. The
      average case fatality rate for the period was 8.3%. The system was sensitive,
      representative, and acceptable. The predictive value positive was 100% from 2010
      to 2014 and 63.3% in 2015. Data quality was good, but timeliness of reporting was
      poor. CONCLUSIONS: The enhanced meningitis surveillance system in Yendi
      Municipality is achieving most of its objectives. However, financial constraints
      and poor personnel motivation pose threats to the sustainability of the system.

PMID- 28438134
TI  - Poly I:C induces collective migration of HaCaT keratinocytes via IL-8.
AB  - BACKGROUND: Delayed wound healing reduces the quality of life (QOL) of patients.
      Thus, understanding the mechanism of wound healing is indispensable for better
      management. However, the role of innate immunity in wound healing is thus far
      unknown. Recently the involvement of TLR3 in wound healing has been evaluated.
      The systemic administration of polyriboinosinic-polyribocytidylic acid (poly I:C
      ; a substitute for viral dsRNA and a ligand of toll-like receptor 3), enhances
      wound healing in vivo. The aim of this study is to improve our understanding of
      the link between innate immunity and human wound healing, particularly in re
      epithelialization. RESULTS: The present study showed that poly I:C significantly
      accelerated collective HaCaT cell migration in a scratch assay. Poly I:C also
      increased IL-8 and bFGF production, and anti-IL-8 antibodies significantly
      inhibited the migration caused by poly I:C. Human recombinant IL-8 also
      accelerated collective HaCaT cell migration. An immunofluorescence assay and
      enzyme-linked immunosorbent assay (ELISA) also revealed that poly I:C decreased E
      cadherin protein levels and increased vimentin protein levels, and anti-IL-8
      antibody reversed this effect. In contrast, nucleic/cytosolic protein ratios of
      Snail 1 were unchanged in all tested conditions. CONCLUSION: Our findings
      demonstrated that poly I:C accelerated collective HaCaT cell migration via
      autocrine/paracrine secretions of IL-8 and the subsequent incomplete epithelial
      mesenchymal transition (EMT). Our findings provide a new strategy for wound
      healing by regulating innate immune systems in re-epithelialization.

PMID- 28438135
TI  - A passive mutualistic interaction promotes the evolution of spatial structure
      within microbial populations.
AB  - BACKGROUND: While mutualistic interactions between different genotypes are
      pervasive in nature, their evolutionary origin is not clear. The dilemma is that,
      for mutualistic interactions to emerge and persist, an investment into the
      partner genotype must pay off: individuals of a first genotype that invest
      resources to promote the growth of a second genotype must receive a benefit that
      is not equally accessible to individuals that do not invest. One way for
      exclusive benefits to emerge is through spatial structure (i.e., physical
      barriers to the movement of individuals and resources). RESULTS: Here we propose
      that organisms can evolve their own spatial structure based on physical
      attachment between individuals, and we hypothesize that attachment evolves when
      spatial proximity to members of another species is advantageous. We tested this
      hypothesis using experimental evolution with combinations of E. coli strains that
      depend on each other to grow. We found that attachment between cells repeatedly
      evolved within 8 weeks of evolution and observed that many different types of
      mutations potentially contributed to increased attachment. CONCLUSIONS: We
      postulate a general principle by which passive beneficial interactions between
      organisms select for attachment, and attachment then provides spatial structure
      that could be conducive for the evolution of active mutualistic interactions.

PMID- 28438136
TI  - Normalized long read RNA sequencing in chicken reveals transcriptome complexity
      similar to human.
AB  - BACKGROUND: Despite the significance of chicken as a model organism, our
      understanding of the chicken transcriptome is limited compared to human. This
      issue is common to all non-human vertebrate annotations due to the difficulty in
      transcript identification from short read RNAseq data. While previous studies
      have used single molecule long read sequencing for transcript discovery, they did
      not perform RNA normalization and 5'-cap selection which may have resulted in
      lower transcriptome coverage and truncated transcript sequences. RESULTS: We
      sequenced normalised chicken brain and embryo RNA libraries with Pacific
      Bioscience Iso-Seq. 5' cap selection was performed on the embryo library to
      provide methodological comparison. From these Iso-Seq sequencing projects, we
      have identified 60 k transcripts and 29 k genes within the chicken transcriptome.
      Of these, more than 20 k are novel lncRNA transcripts with ~3 k classified as
      sense exonic overlapping lncRNA, which is a class that is underrepresented in
      many vertebrate annotations. The relative proportion of alternative transcription
      events revealed striking similarities between the chicken and human
      transcriptomes while also providing explanations for previously observed genomic
      differences. CONCLUSIONS: Our results indicate that the chicken transcriptome is
      similar in complexity compared to human, and provide insights into other
      vertebrate biology. Our methodology demonstrates the potential of Iso-Seq
      sequencing to rapidly expand our knowledge of transcriptomics.

PMID- 28438137
TI  - Case report of Plasmodium ovale curtisi malaria in Sri Lanka: relevance for the
      maintenance of elimination status.
AB  - BACKGROUND: Following its recent certification as malaria-free, imported
      infections now pose the greatest threat for maintaining this status in Sri Lanka.
      Imported infections may also introduce species that are uncommon or not
      previously endemic to these areas. We highlight in this case report the
      increasing importance of less common malaria species such as Plasmodium ovale in
      elimination settings and discuss its relevance for the risk of malaria resurgence
      in the country. CASE PRESENTATION: A 41-year-old patient from southern Sri Lanka
      was diagnosed with malaria after 8 days of fever. Microscopy of blood smears
      revealed parasites morphologically similar to P. vivax and the rapid diagnostic
      test was indicative of non-P. falciparum malaria. He was treated with chloroquine
      over 3 days and primaquine for 14 days. He was negative for malaria at a one-year
      follow-up. Molecular testing performed subsequently confirmed that infection was
      caused by P. ovale curtisi. The patient gave a history of P. vivax malaria
      treated with chloroquine and primaquine. He also provided a history of travel to
      malaria endemic regions, including residing in Liberia from May 2012 to November
      2013, throughout which he was on weekly malaria prophylaxis with mefloquine. He
      had also visited India on an eight-day Buddhist pilgrimage tour in September 2014
      without malaria prophylaxis. CONCLUSIONS: It is crucial that every case of
      malaria is investigated thoroughly and necessary measures taken to prevent re
      introduction of malaria. Accurate molecular diagnostic techniques need to be
      established in Sri Lanka for the screening and diagnosis of all species of human
      malaria infections, especially those that may occur with low parasitemia and are
      likely to be undetected using the standard techniques currently in use. In
      addition, ascertaining whether an infection occurred through local transmission
      or by importation is critical in the implementation of an effective plan of
      action in the country. This new era emphasizes the global nature of regional
      malaria elimination. Increasing global surveillance and tool development are
      necessary in order to "fingerprint" parasites and identify their origin.

PMID- 28438138
TI  - Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and
      children with systemic inflammatory syndrome: a meta-analysis.
AB  - BACKGROUND: A number of biomarkers have been studied for the diagnosis of sepsis
      in paediatrics, but no gold standard has been identified. Procalcitonin (PCT) was
      demonstrated to be an accurate biomarker for the diagnosis of sepsis in adults
      and showed to be promising in paediatrics. Our study reviewed the diagnostic
      accuracy of PCT as an early biomarker of sepsis in neonates and children with
      suspected sepsis. METHODS: A comprehensive literature search was carried out in
      Medline/Pubmed, Embase, ISI Web of Science, CINAHL and Cochrane Library, for
      studies assessing PCT accuracy in the diagnosis of sepsis in children and
      neonates with suspected sepsis. Studies in which the presence of infection had
      been confirmed microbiologically or classified as "probable" by chart review were
      included. Studies comparing patients to healthy subjects were excluded. We
      analysed data on neonates and children separately. Our primary outcome was the
      diagnostic accuracy of PCT at the cut-off of 2-2.5 ng/ml, while as secondary
      outcomes we analysed PCT cut-offs <2 ng/ml and >2.5 ng/ml. Pooled sensitivities
      and specificities were calculated by a bivariate meta-analysis and heterogeneity
      was graphically evaluated. RESULTS: We included 17 studies, with a total of 1408
      patients (1086 neonates and 322 children). Studies on neonates with early onset
      sepsis (EOS) and late onset sepsis (LOS) were grouped together. In the neonatal
      group, we calculated a sensitivity of 0.85, confidence interval (CI) (0.76; 0.90)
      and specificity of 0.54, CI (0.38; 0.70) at the PCT cut-off of 2.0-2.5 ng/ml. In
      the paediatric group it was not possible to undertake a pooled analysis at the
      PCT cut-off of 2.0-2.5 ng/ml, due to the paucity of the studies. CONCLUSIONS: PCT
      shows a moderate accuracy for the diagnosis of sepsis in neonates with suspected
      sepsis at the cut-off of 2.0-2.5 ng/ml. More studies with high methodological
      quality are warranted, particularly in neonates, studies considering EOS and LOS
      separately are needed to improve specificity. TRIAL REGISTRATION: PROSPERO
      Identifier: CRD42016033809 . Registered 30 Jan 2016.

PMID- 28438139
TI  - Digital CXR with computer aided diagnosis versus symptom screen to define
      presumptive tuberculosis among household contacts and impact on tuberculosis
      diagnosis.
AB  - BACKGROUND: Household (HH) contact tracing is a strategy that targets high risk
      groups for TB. Symptom based screening is the standard used to identify HH
      contacts at risk for TB during HH contact tracing for TB. However, this strategy
      may be limited due to poor performance in predicting TB. The objective of this
      study was to compare CXR with Computer Aided Diagnosis (CAD) against symptom
      screen for defining presumptive TB and how TB detection changes with each method.
      METHODS: Household contacts of consecutive index bacteriologically confirmed TB
      cases were visited by study teams and given TB/HIV education to raise awareness
      of the risk of TB following close contact with a TB patient. Contacts were
      encouraged to visit the health facility for screening; where symptoms history was
      obtained and opt out HIV testing was provided as part of the screening process.
      CXR was offered to all regardless of symptoms, followed by definitive sputum test
      with either Xpert MTB RIF or smear microscopy. RESULTS: Among 919 HH contacts
      that presented for screening, 865 were screened with CXR and 464 (53.6%) had an
      abnormal CXR and the rest had a normal CXR. Among 444 HH contacts with valid
      sputum results, 274 (61.7%) were symptom screen positive and 255 (57.4%) had an
      abnormal CXR. Overall, TB was diagnosed in 32/444 (7.2%); 13 bacteriologically
      unconfirmed and 19 bacteriologically confirmed. Of 19 bacteriologically confirmed
      TB 8 (42.1%) were symptom screen negative contacts with an abnormal CXR and these
      6/8 (75.0%) were HIV positive. Among the 13 bacteriologically unconfirmed TB
      cases, 7 (53.8%) were HIV positive and all had an abnormal CXR. CONCLUSION:
      Symptom screen if used alone with follow on definitive TB testing only for
      symptom screen positive individuals would have missed eight of the 19 confirmed
      TB cases detected in this study. There is need to consider use of other screening
      strategies apart from symptom screen alone for optimal rule out of TB especially
      in HIV positive individuals that are at greatest risk of TB and present
      atypically.

PMID- 28438141
TI  - Prevalence of Toxocara antibodies among patients clinically suspected to have
      ocular toxocariasis: A retrospective descriptive study in Sri Lanka.
AB  - BACKGROUND: Human toxocariasis, caused by Toxocara canis, T. cati, and T.
      vitulorum of dogs, cats and ruminants respectively, is recognized as an important
      zoonotic infection worldwide. The typical clinical syndromes of toxocariasis in
      humans are ocular larva migrans (OLM) and visceral larva migrans (VLM). The most
      commonly affected sites of OLM are the peripheral retina and/or vitreous humor.
      In Sri Lanka, there is a dearth of information on prevalence of ocular infection
      in our population. Therefore, the present study was carried out to determine the
      prevalence of Toxocara antibodies in suspected OLM patients and to describe
      demographic factors and clinical manifestations of seropositive patients. A total
      of 250 clinically suspected ocular toxocariasis cases referred by consultant eye
      surgeons to the Department of Parasitology, University of Peradeniya were studied
      between the years 1995 to April 2015. METHODS: Data (age, sex, fundoscopic
      findings) were gathered from the referral letters. Each serum sample was
      subjected to Toxocara excretory - secretory antigen ELISA (TES - ELISA). RESULTS:
      Out of the 250 cases, 155 (62%) were seropositive. The age range of the
      seropositive cases was 1 to 78 years with the mean age of 27 years. The highest
      seropositivity (25/155) was observed within the age group of 10 to 14 years. The
      most frequent clinical presentation of seropositive OLM cases were unilateral
      reduced vision and red eye. The other symptoms include tearing, photophobia and
      leukokoria. A high proportion of seropositive OLM cases had uveitis (34.19%)
      followed by reduced vision (21.94%), vitritis (12.9%) and choroiditis (7.74%).
      However none of these clinical manifestations were significantly associated with
      TES-ELISA seropositivity except vitreits (X2 = 8.557, p = 0.003). CONCLUSION: In
      conclusion, the results of this study showed high seroprevalence of toxocariasis
      among clinically suspected OLM cases confirming the toxoplasmic etiology. This
      high rate of Toxocara seropositivity in ocular patients should alert
      ophthalmologists in Sri Lanka to include toxocariasis in the differential
      diagnosis of ocular diseases presented with the symptoms and signs stated above.

PMID- 28438140
TI  - A universal genome sequencing method for rotavirus A from human fecal samples
      which identifies segment reassortment and multi-genotype mixed infection.
AB  - BACKGROUND: Genomic characterization of rotavirus (RoV) has not been adopted at
      large-scale due to the complexity of obtaining sequences for all 11 segments,
      particularly when feces are used as starting material. METHODS: To overcome these
      limitations, we developed a novel RoV capture and genome sequencing method
      combining commercial enzyme immunoassay plates and a set of routinely used
      reagents. RESULTS: Our approach had a 100% success rate, producing >90% genome
      coverage for diverse RoV present in fecal samples (Ct < 30). CONCLUSIONS: This
      method provides a novel, reproducible and comparatively simple approach for
      genomic RoV characterization and could be scaled-up for use in global RoV
      surveillance systems. TRIAL REGISTRATION (PROSPECTIVELY REGISTERED): Current
      Controlled Trials ISRCTN88101063 . Date of registration: 14/06/2012.

PMID- 28438142
TI  - Alpha molecular epidemiological analysis of adenoviruses from excess
      conjunctivitis cases.
AB  - BACKGROUND: Tauo perform a molecular epidemiological analysis of viral
      conjunctivitis among excess conjunctivitis cases recorded at the University
      Hospital of Patras, Greece, for the period March to June 2012. METHODS: A
      structured questionnaire containing demographic and clinical data was developed
      in order to collect retrospective data on the cases. Eye swab specimens were
      collected and molecular detection of adenoviruses was performed by nested PCR.
      Positive results were confirmed by sequencing. To determine the relatedness
      between the isolated sequences, a phylogenetic analysis was conducted. RESULTS:
      The epidemiological analysis (including retrospective data) included 231
      conjunctivitis cases (47.1% male, and 52.8% female). Based on clinical features
      205 of the cases were diagnosed of viral origin (46.3% male and 53.7% female), 4
      of bacterial origin (50% male and 50% female) while 22 were undefined
      conjunctivitis. The outbreak excess cases (included 156 cases) affected all age
      groups regardless gender predilection. For the positive samples indicated that 29
      samples (72.5%) were AdV17, and 5 (12.5%) as AdV54. CONCLUSIONS: Molecular
      analysis could define the cause of viral conjunctivitis, while epidemiological
      data contributed to the assessment of the risk factors and underlined possible
      preventive measures. This study is one of the very few on viral conjunctivitis in
      Greece. This outbreak underscores the need for a national surveillance system for
      acute infectious conjunctivitis outbreaks. The epidemiological as well as
      molecular investigation on HAdV ocular infections is rather absent in Greece,
      which has no surveillance system for viral conjunctivitis.

PMID- 28438143
TI  - Erratum to: High pre-diagnosis attrition among patients with presumptive MDR-TB:
      an operational research from Bhopal district, India.

PMID- 28438144
TI  - Development and effectiveness of a mobile phone application conducting health
      behavioral intervention among men who have sex with men, a randomized controlled
      trial: study protocol.
AB  - BACKGROUND: Behavioral intervention is a key approach to HIV prevention among men
      who have sex with men (MSM). Widespread use of mobile phones provide us with
      novel opportunities to decrease HIV infection and transmission of MSM. The
      objective of the study was to design and develop a mobile phone application (app)
      aims to conduct behavioral intervention to MSM and to evaluate the efficacy of
      the app-based intervention compared to usual care, to analyze cost-effectiveness
      and mechanism of the intervention. METHODS: This study involves 2 phases, phase 1
      use qualitative method and phase 2 is a randomized controlled trial lasting for
      18 months, they will be conducted in Chagnsha, Hunan Province, China. Phase 1 is
      to design and develop the app, procedures including retrieval of domestic apps
      related to prevention and treatment about HIV and sexually transmitted diseases
      (HIV/STDs), personal interviews with MSM about preferences and functional needs
      of the HIV prevention app, multidisciplinary experts focused group discussions of
      the app, software engineers' development and users test of the app will be
      performed. In phase 2, we will recruit 800 MSM by cooperating with the local
      center of disease control and prevention and nongovernmental organizations, and
      divide them into intervention and control group evenly. Intervention group
      participants will receive app-based HIV prevention. Control group participants
      will be provided with usual care including HIV/STDs knowledge brochure and free
      voluntary counseling services. Data will be collected at baseline, 6, 12 and 18
      months since subject's participation. Effectiveness of the intervention includes
      HIV/STDs infection rates, adherence to regularly HIV testing, sexual risk
      behavior, consistent condom use and relative risk of HIV infection. Cost
      effectiveness will be analyzed by decision-analytic modeling, and mechanism
      analysis of this app-based intervention will be performed by path analysis.
      DISCUSSION: This will be the first study of its kind in China to develop an app
      and implement app-based HIV prevention intervention among MSM. It is of great
      potential to determine whether app-based intervention is a cost-effective way to
      decrease HIV infection among MSM and explore intervention mechanism with an
      accurate method. TRIAL REGISTRATION: Chinese Clinical Trial Register ( ChiCTR-IOR
      15006724 ). Registered 10 July 2015.

PMID- 28438145
TI  - Insights into the availability and distribution of oral artemisinin monotherapy
      in Myanmar: evidence from a nationally representative outlet survey.
AB  - BACKGROUND: The containment of artemisinin resistance in Myanmar, historically an
      important probable origin and route of anti-malarial resistance to the India sub
      continent and beyond, is crucial to global malaria control and elimination. This
      paper describes what is currently known about the sale and distribution of oral
      artemisinin monotherapy (AMT) across Myanmar, where this medicine is commonly
      found. METHODS: A nationally representative 2015 outlet survey was conducted in
      the private sector, and among community health workers across four geographical
      domains. A national sample of outlets was screened for availability of malaria
      testing and treatment, and an audit was completed for all anti-malarials.
      RESULTS: A total of 3859 outlets across Myanmar had an anti-malarial in stock on
      the day of survey. Of the 3859 anti-malarial stocking outlets, 988 outlets
      stocked oral AMT. Availability of oral AMT was highest among outlets in the
      Western border (36.8%) versus other domains (Eastern, 15.0%; Central, 19.3%
      Coastal, 10.7%). Over 90% of the oral AMT service delivery points were private
      sector outlets: general retailers (49.4%), pharmacies (23.5%), and itinerant drug
      vendors (14.2%). Eleven unique oral AMT products were audited. The most common
      product audited was Artesunate(r), manufactured by Mediplantex in Vietnam, which
      accounted for 79.9% of the oral AMT market share. Other oral AMT products were
      manufactured in China and in Myanmar. Over 60% of oral AMT products had a shelf
      life at purchase of greater than 2 years and only 14.7% were expired. The median
      number of oral AMT tablets typically dispensed to treat malaria was two tablets,
      approximately one tenth of a full adult course. The median price of a 50 mg
      tablet was $0.16. CONCLUSIONS: Given the high availability and distribution of
      oral AMT, it is possible that Myanmar has become the last remaining viable market
      for any oral AMT in the region for manufacturers. National and international
      organizations need to act quickly and effectively to stop the production and
      distribution to both improve malaria control within Myanmar and reduce risk of
      artemisinin resistance spreading to India and Africa.

PMID- 28438146
TI  - Correlates associated with participation in physical activity among adults: a
      systematic review of reviews and update.
AB  - BACKGROUND: Understanding which factors influence participation in physical
      activity is important to improve the public health. The aim of the present review
      of reviews was to summarize and present updated evidence on personal and
      environmental factors associated with physical activity. METHODS: MEDLINE and
      EMBASE were searched for reviews published up to 31 Jan. 2017 reporting on
      potential factors of physical activity in adults aged over 18 years. The quality
      of each review was appraised with the Assessing the Methodological Quality of
      Systematic Reviews (AMSTAR) checklist. The corrected covered area (CCA) was
      calculated as a measure of overlap for the primary publications in each review.
      RESULTS: Twenty-five articles met the inclusion criteria which reviewed 90
      personal and 27 environmental factors. The average quality of the studies was
      moderate, and the CCA ranged from 0 to 4.3%. For personal factors, self-efficacy
      was shown as the strongest factor for participation in physical activity (7 out
      of 9). Intention to exercise, outcome expectation, perceived behavioral control
      and perceived fitness were positively associated with physical activity in more
      than 3 reviews, while age and bad status of health or fitness were negatively
      associated with participation in physical activity in more than 3 reviews. For
      environmental factors, accessibility to facilities, presence of sidewalks, and
      aesthetics were positively associated with participation in physical activity.
      CONCLUSIONS: The findings of this review of reviews suggest that some personal
      and environmental factors were related with participation in physical activity.
      However, an association of various factors with physical activity could not be
      established because of the lack of primary studies to build up the organized
      evidence. More studies with a prospective design should be conducted to
      understand the potential causes for physical activity.

PMID- 28438147
TI  - Leukocyte telomere length and depression, anxiety and stress and adjustment
      disorders in primary health care patients.
AB  - BACKGROUND: The primary aim was to examine possible differences in telomere
      length between primary health care patients, with depression, anxiety or stress
      and adjustment disorders, and healthy controls. The second aim was to examine the
      association between telomere length and baseline characteristics in the patients.
      The third aim was to examine the potential effects of the 8-week treatments
      (mindfulness-based group therapy or treatment as usual, i.e. mostly cognitive
      based therapy) on telomere length, and to examine whether there was a difference
      in the potential effect on telomere length between the two groups. METHODS: A
      total of 501 individuals including 181 patients (aged 20-64 years), with
      depression, anxiety and stress and adjustment disorders, and 320 healthy controls
      (aged 19-70 years) were recruited in the study. Patient data were collected from
      a randomized controlled trial comparing mindfulness-based group therapy with
      treatment as usual. We isolated genomic DNA from blood samples, collected at
      baseline and after the 8-week follow-up. Telomere length was measured by
      quantitative real-time (qRT)-PCR. RESULTS: Telomere length was significantly
      shorter in the patients (mean = 0.77 +/- 0.12,), compared to the controls (mean =
      0.81 +/- 0.14) (p = 0.006). The difference in telomere length remained
      significant after controlling for age and sex. Old age, male sex and being
      overweight were associated with shorter telomere length. There was no significant
      difference in telomere length between baseline and at the 8-week follow-up in any
      of the treatment groups and no difference between the two groups. CONCLUSION: Our
      findings confirm that telomere length, as compared with healthy controls, is
      shortened in patients with depression, anxiety and stress and adjustment
      disorders. In both groups (mindfulness-based group therapy or treatment as
      usual), the telomere length remained unchanged after the 8-week treatment/follow
      up and there was no difference between the two groups. TRIAL REGISTRATION:
      (ClinicalTrials.gov ID: NCT01476371 ) Registered November 11, 2011.

PMID- 28438149
TI  - Anti-depressant and anxiolytic potential of Acacia hydaspica R. Parker aerial
      parts extract: Modulation of brain antioxidant enzyme status.
AB  - BACKGROUND: Oxidative stress may link to psychiatric disorders, and is being
      regarded as a plausible mechanism that can affect the regulation of these
      illnesses. The present study was undertaken to investigate the antidepressant and
      anxiolytic potential of A. hydaspica R. parkers. Brain oxidative stress enzyme
      levels were analyzed to correlate depression and stress with brain antioxidant
      status. METHODS: Antidepressant and anxiolytic effect of methanol extract of A.
      hydaspica and its derived soluble fractions [n-hexane (AHH), ethyl-acetate (AHE),
      chloroform (AHC), n-butanol (AHB) and remaining aqueous fraction (AHA)] was
      investigated by using three behavioral models; the Forced swimming test, Tail
      suspension test and Elevated plus-maze test (EPM). Chronic unpredictable mild
      stress (CMS) was employed to induce stress in rats. AHM and AHE (200 mg/kg, p.o),
      fluoxetine (5 mg/kg, i.p) and diazepam (DZM) (1 mg/kg, p.o) were administered
      during the 7 day stress exposure period, and rats were assessed for
      antidepressant and anxiolytic behavioral despair paradigms. Antioxidant enzymes
      and oxidative stress markers were measured in brain tissue of depressed rats.
      Phytochemical analysis was done by GCMS experimentation. RESULTS: AHM and AHE
      (acute dose) significantly (p < 0.0001) reduced the immobility time and
      ameliorated climbing behavior as compared to the control in FST and TST, and
      similar to fluoxetine. AHM and AHE showed significant (p < 0.0001) anxiolytic
      potential in EPM, and comparable to DZM (1 mg/kg b.w., i.p). Significant decrease
      in antioxidant enzyme levels and increase in MDA, H2O2 and NO level were observed
      in stressed rats. AHM and AHE (for 7 days/CMS) significantly improved behavior in
      FST, TST and EPMT. Treatment also improved antioxidant enzyme level and
      controlled the oxidative stress markers in brain tissues. GCMS analysis indicated
      the presence of 10 different chemical constituents in A. hydaspica. CONCLUSION:
      The present study revealed that A. hydaspica exerts an antidepressant and
      anxiolytic effect by improving brain antioxidant status. The observed activities
      might be due to the presence of diverse phytochemicals.

PMID- 28438148
TI  - Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and
      offspring birthweight.
AB  - BACKGROUND: Cadmium (Cd), lead (Pb) and arsenic (As) are common environmental
      contaminants that have been associated with lower birthweight. Although some
      essential metals may mitigate exposure, data are inconsistent. This study sought
      to evaluate the relationship between toxic metals, nutrient combinations and
      birthweight among 275 mother-child pairs. METHODS: Non-essential metals, Cd, Pb,
      As, and essential metals, iron (Fe), zinc (Zn), selenium (Se), copper (Cu),
      calcium (Ca), magnesium (Mg), and manganese (Mn) were measured in maternal whole
      blood obtained during the first trimester using inductively coupled plasma mass
      spectrometry. Folate concentrations were measured by microbial assay. Birthweight
      was obtained from medical records. We used quantile regression to evaluate the
      association between toxic metals and nutrients due to their underlying wedge
      shaped relationship. Ordinary linear regression was used to evaluate associations
      between birth weight and toxic metals. RESULTS: After multivariate adjustment,
      the negative association between Pb or Cd and a combination of Fe, Se, Ca and
      folate was robust, persistent and dose-dependent (p < 0.05). However, a
      combination of Zn, Cu, Mn and Mg was positively associated with Pb and Cd levels.
      While prenatal blood Cd and Pb were also associated with lower birthweight. Fe,
      Se, Ca and folate did not modify these associations. CONCLUSION: Small sample
      size and cross-sectional design notwithstanding, the robust and persistent
      negative associations between some, but not all, nutrient combinations with these
      ubiquitous environmental contaminants suggest that only some recommended nutrient
      combinations may mitigate toxic metal exposure in chronically exposed
      populations. Larger longitudinal studies are required to confirm these findings.

PMID- 28438150
TI  - Intermittent parathyroid hormone improve bone microarchitecture of the mandible
      and femoral head in ovariectomized rats.
AB  - BACKGROUND: Intermittent parathyroid hormone (PTH) can be used to treat
      osteoporosis of the spine and hip. However, whether it can be used to treat
      osteoporosis of the mandible is unclear. The purpose of this study was to explore
      the influence of applying intermittent PTH to ovariectomized rats on the
      trabecular bone microarchitecture of the mandible and femoral head. METHODS:
      Eighteen female rats were divided into three groups: the healthy group,
      ovariectomized (OVX) group, and OVX + PTH group. The OVX group and OVX + PTH
      group had an OVX at 8 weeks of age. The OVX + PTH group received intermittent PTH
      therapy for 12 weeks. The mandibles and femurs of all rats were removed at 20
      weeks and were then scanned using microcomputed tomography (micro-CT). RESULTS:
      From the micro-CT analysis, the trabecular bone microarchitecture of the mandible
      and femoral head are offered as follows: (1) The bone volume fraction and
      trabecular thickness in the OVX group were lower than those in the healthy group.
      (2) The bone volume fraction and trabecular thickness in the OVX + PTH group
      approximated those in the healthy group. CONCLUSION: The conclusions of this
      study regarding the trabecular bone microarchitecture of the mandible and femoral
      head are offered as follows: (1) The BV/TV and TbTh in the OVX group were lower
      than those in the healthy group. (2) The BV/TV and TbTh in the OVX + PTH group
      approximated those in the healthy group, therefore, intermittent PTH displayed
      high efficacy for treating femoral or mandibular deterioration of bone
      microstructure resulting from loss of ovarian function. Osteoporosis of the femur
      or mandible in the rats was ameliorated by intermittent PTH therapy.

PMID- 28438151
TI  - Effect of platelet rich fibrin on edema and pain following third molar surgery: a
      split mouth control study.
AB  - BACKGROUND: To evaluate the efficacy of platelet-rich fibrine (PRF) on
      postoperative edema and pain after impacted mandibular third molar surgery.
      METHODS: The prospective study was comprised 30 patients who presented for the
      removal of bilateral impacted mandibular third molar teeth. After extraction, the
      sockets were filled with PRF or without PRF in the study and control groups,
      respectively. Postoperative edema was measured with a flexible tape measure by
      calculating the distance between several facial landmarks on postoperative days
      two and seven. Postoperative pain was evaluated with a line-type visual analogue
      scale (VAS) and a verbal scale (VRS). SPSS version 20.0 was used for data
      analysis. RESULTS: Both groups recorded significant improvement compared to the
      baseline levels in almost all of the outcome variables. There was no
      statistically significant difference between the study and control groups (p >
      0.05). CONCLUSIONS: Using or not using PRF to reduce postoperative pain and edema
      in third molar surgery was equally successful. TRIAL REGISTRATION: This study was
      retrospectively registered at the ISRCTN registry ( ISRCTN16849867 ) on 6 March
      2017.

PMID- 28438152
TI  - A cluster randomised control trial to evaluate the effectiveness and cost
      effectiveness of the Italian medicines use review (I-MUR) for asthma patients.
AB  - BACKGROUND: The economic burden of asthma, which relates to the degree of
      control, is ?5 billion annually in Italy. Pharmacists could help improve asthma
      control, reducing this burden. This study aimed to evaluate the effectiveness and
      cost-effectiveness of Medicines Use Reviews provided by community pharmacists in
      asthma. METHODS: This cluster randomised, multi-centre, controlled trial in adult
      patients with asthma was conducted in 15 of the 20 regions of Italy between
      September 2014 and July 2015. After stratification by region, community
      pharmacists were randomly allocated to group A (trained in and delivered the
      intervention at baseline) or B (training and delivery 3 months later), using
      computerised random number generation in blocks of 10. Each recruited up to five
      patients, with both groups followed for 9 months. The intervention consisted of a
      systematic, structured face-to-face consultation with a pharmacist, covering
      asthma symptoms, medicines used, attitude towards medicines and adherence,
      recording pharmacist-identified pharmaceutical care issues (PCIs). The primary
      outcome was asthma control, assessed using the Asthma-Control-Test (ACT) score
      (ACT >= 20 represents good control). Secondary outcomes were: number of active
      ingredients, adherence, cost-effectiveness compared with usual care. Although
      blinding was not possible for either pharmacists or patients, assessment of
      outcomes was conducted by researchers blind to group allocation. RESULTS: Numbers
      of pharmacists and patients enrolled were 283 (A = 136; B = 147) and 1263 (A =
      600; B = 663), numbers completing were 201 (A = 97; B = 104) and 816 (A = 400; B
      = 416), respectively. Patients were similar in age and gender and 56.13%
      (458/816) had poor/partial asthma control. Pharmacists identified 1256 PCIs (mean
      1.54/patient), mostly need for education, monitoring and potentially ineffective
      therapy. Median ACT score at baseline differed between groups (A = 19, B = 18; p
      < 0.01). Odds ratio for improved asthma control was 1.76 (95% CI 1.33-2.33) and
      number needed to treat 10 (95% CI 6-28). Number of active ingredients reduced by
      7.9% post-intervention (p < 0.01). Adherence improved by 35.4% 3 months post
      intervention and 40.0% at 6 months (p < 0.01). The probability of the
      intervention being more cost-effective than usual care was 100% at 9 months.
      CONCLUSIONS: This community pharmacist-based intervention demonstrated both
      effectiveness and cost-effectiveness. It has since been implemented as the first
      community pharmacy cognitive service in Italy. TRIAL REGISTRATION: TRN:
      ISRCTN72438848 (registered 5th January 2015, retrospectively).

PMID- 28438153
TI  - Damage to the macula associated with LED-derived blue laser exposure: A case
      report.
AB  - BACKGROUND: Light emitting diodes laser is emerging as an important source of
      light replacing conventional lights. It is widely used for illumination in the
      bar where young people love to go. But not everyone knows about the light damage
      to the eye especially to the macula. In this article, we report the case of a
      macular damage induced by LED-derived blue laser in a bar, studied with optical
      coherence tomography (OCT) to evaluate the retinal lesion and multifocal
      electroretinography (mfERG) to evaluate functional damage. CASE PRESENTATION:
      Four days after the photo injury to the right eye, the visual acuity was 0.5.
      Funduscopy revealed a round red lesion in the macula of the right eye.
      Fluorescein angiography (FA) revealed no leakage. OCT revealed a deficiency in
      the center of the fovea. MfERG revealed a reduction of the peak value in the
      right eye compared to the left eye. One month later, although the vision was 1.0
      in the right eye, OCT revealed a hyporeflectivity of the ellipsoid zone. MfERG
      still showed a reduction of the peak value in the right eye compared to the left
      eye. CONCLUSION: We believe that general knowledge about laser injuries to the
      eye should be realized widely. We also think in cases of macular laser damage,
      the recovery of vision can not demonstrate the recovery of the function of
      photoreceptors.

PMID- 28438154
TI  - Network-based analysis reveals novel gene signatures in peripheral blood of
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third
      leading cause of death and there is a huge unmet clinical need to identify
      disease biomarkers in peripheral blood. Compared to gene level differential
      expression approaches to identify gene signatures, network analyses provide a
      biologically intuitive approach which leverages the co-expression patterns in the
      transcriptome to identify modules of co-expressed genes. METHODS: A weighted gene
      co-expression network analysis (WGCNA) was applied to peripheral blood
      transcriptome from 238 COPD subjects to discover co-expressed gene modules. We
      then determined the relationship between these modules and forced expiratory
      volume in 1 s (FEV1). In a second, independent cohort of 381 subjects, we
      determined the preservation of these modules and their relationship with FEV1.
      For those modules that were significantly related to FEV1, we determined the
      biological processes as well as the blood cell-specific gene expression that were
      over-represented using additional external datasets. RESULTS: Using WGCNA, we
      identified 17 modules of co-expressed genes in the discovery cohort. Three of
      these modules were significantly correlated with FEV1 (FDR < 0.1). In the
      replication cohort, these modules were highly preserved and their FEV1
      associations were reproducible (P < 0.05). Two of the three modules were
      negatively related to FEV1 and were enriched in IL8 and IL10 pathways and
      correlated with neutrophil-specific gene expression. The positively related
      module, on the other hand, was enriched in DNA transcription and translation and
      was strongly correlated to CD4+, CD8+ T cell-specific gene expression.
      CONCLUSIONS: Network based approaches are promising tools to identify potential
      biomarkers for COPD. TRIAL REGISTRATION: The ECLIPSE study was funded by
      GlaxoSmithKline, under ClinicalTrials.gov identifier NCT00292552 and GSK No.
      SCO104960.

PMID- 28438155
TI  - The malaria testing and treatment landscape in the southern Lao People's
      Democratic Republic (PDR).
AB  - BACKGROUND: In the context of national and regional goals to eliminate malaria by
      2030, the Center for Malaria Parasitology and Entomology in the Lao PDR is
      implementing strategies to ensure all malaria cases are detected and
      appropriately treated with first-line artemisinin combination therapy, artemether
      lumefantrine (AL). Timely and relevant evidence to inform policies and strategies
      is needed to ensure the most effective and efficient use of resources, and to
      accelerate progress towards elimination goals. A 2015 outlet survey conducted in
      five provinces of the southern Lao PDR was the first of its kind to study the
      total market for malaria treatments and diagnostics. The sub-national outlet
      survey was designed to describe the market and to assess public and private
      sector readiness and performance for malaria case management. Additionally, key
      indicators were estimated among private outlets within districts with and without
      a Public Private Mix (PPM) programme. RESULTS: Over half of anti-malarial
      stockists were public sector (65.1%). In the private sector, pharmacies most
      commonly stocked anti-malarials, although anti-malarials were also found in
      private health facilities, drug stores, general retailers, and itinerant drug
      vendors. Nearly all anti-malarial stocking public health facilities had AL
      (99.5%) and 90.8% had confirmatory testing. Fewer than half of anti-malarial
      stocking private outlets stocked AL (40.8%) and malaria testing (43.5%).
      Chloroquine has not been a first-line treatment for Plasmodium falciparum malaria
      since 2005 and Plasmodium vivax since 2011 yet private sector availability was
      77.6% and chloroquine accounted for 62.2% of the total anti-malarial market
      share. AL and confirmatory testing availability were higher in private outlets in
      PPM (68.1, 72.6%) versus non-PPM districts (2.5, 12.1%). Chloroquine was
      available in 63.6% of PPM and 96.7% of non-PPM-district outlets, and was the most
      commonly distributed anti-malarial among private outlets in both PPM (61.7%) and
      non-PPM districts (99.1%). CONCLUSIONS: Public sector outlets in the southern Lao
      PDR are typically equipped to test and appropriately treat malaria. There is need
      to address widespread private sector availability and distribution of
      chloroquine. The PPM programme has improved private provider readiness to manage
      malaria according to national guidelines. However, supporting interventions to
      address provider and consumer behaviours are needed to further drive uptake.

PMID- 28438156
TI  - Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology
      of adult-onset, non-insulin-requiring autoimmune diabetes.
AB  - BACKGROUND: In adulthood, autoimmune diabetes can present as non-insulin
      requiring diabetes, termed as 'latent autoimmune diabetes in adults' (LADA). In
      this study, we investigated established type 1 diabetes (T1D) and type 2 diabetes
      (T2D) genetic loci in a large cohort of LADA cases to assess where LADA is
      situated relative to these two well-characterized, classic forms of diabetes.
      METHODS: We tested the association of T1D and T2D GWAS-implicated loci in 978
      LADA cases and 1057 non-diabetic controls of European ancestry using a linear
      mixed model. We then compared the associations of T1D and T2D loci between LADA
      and T1D and T2D cases, respectively. We quantified the difference in genetic risk
      between each given disease at each locus, and also calculated genetic risk scores
      to quantify how genetic liability to T1D and T2D distinguished LADA cases from
      controls. RESULTS: Overall, our results showed that LADA is genetically more
      similar to T1D, with the exception of an association at the T2D HNF1A locus.
      Several T1D loci were associated with LADA, including the major
      histocompatibility complex region, as well as at PTPN22, SH2B3, and INS. Contrary
      to previous studies, the key T2D risk allele at TCF7L2 (rs7903146-T) had a
      significantly lower frequency in LADA cases, suggesting that this locus does not
      play a role in LADA etiology. When constrained on antibody status, the similarity
      between LADA and T1D became more apparent; however, the HNF1A and TCF7L2
      observations persisted. CONCLUSION: LADA is genetically closer to T1D than T2D,
      although the genetic load of T1D risk alleles is less than childhood-onset T1D,
      particularly at the major histocompatibility complex region, potentially
      accounting for the later disease onset. Our results show that the genetic
      spectrum of T1D extends into adult-onset diabetes, where it can clinically
      masquerade as T2D. Furthermore, T2D genetic risk plays a small role in LADA, with
      a degree of evidence for the HNF1A locus, highlighting the potential for genetic
      risk scores to contribute towards defining diabetes subtypes.

PMID- 28438157
TI  - Age, period and cohort effects and the predictors of physical activity and
      sedentary behaviour among Chinese children, from 2004 to 2011.
AB  - BACKGROUND: Very few studies have explored the effects of age, time period, and
      cohort in association with biological, behavioral, economic, and environmental
      factors predictors on physical activity (PA) and sedentary behaviour (SB) among
      Chinese children. METHODS: We used data from a cohort study of the China Health
      and Nutrition Survey (CHNS) between 2004 and 2011 (2004, 2006, 2009 and 2011).
      The outcomes of interest were metabolic equivalent of task (MET) hours per week
      from both active and sedentary activities. Age, gender, individual
      characteristics, household size, asset ownership, and urbanisation were included
      as covariates. Age, period and cohort effects analyses for PA and SB of children
      (6-17 y, n = 3528) was conducted to explicitly assess differences in PA and SB
      due to age vs. period effects, and implicitly assess differences by cohorts due
      to the period-specific experiences across individuals of varying ages. RESULTS:
      The mean age of the sample in each time point fluctuated from 12.6 to 11.3 years
      and PA slightly decreased from 50.0 +/- 63.2 MET hours per week (MET-hr./wk) in
      2004 to 47.1 +/- 54.9 MET-hr./wk. in 2011. However, SB increased from 31.8 +/-
      22.0 MET-hr./wk. to 37.6 +/- 22.2 MET-hr./wk. Girls had lower PA and higher SB
      levels than boys. Controlling for age effects, marginal period effects on PA were
      observed in some survey years. Higher levels of urbanisation and number of
      household computers served as negative and positive predictors for PA and SB,
      respectively. Higher household income was a positive predictor of SB.
      Surprisingly, bigger household size was the only negative predictor of SB (P <
      0.05). CONCLUSIONS: This longitudinal study followed a large cohort of children
      over a significant period of their childhood. We observed potential age and
      secular trends in PA levels. Higher community urbanisation and number of home
      computers were associated with both PA and SB levels. Larger household size was
      the only factor that was negatively associated with SB. These findings shed light
      on health policy and preventative health strategies for China and other countries
      that are now facing similar public health challenges.

PMID- 28438158
TI  - Prevalence of helicobacter pylori infection among children living in a rural
      setting in Sub-Saharan Africa.
AB  - BACKGROUND: Helicobacter pylori infection affects more than half of the world's
      population. It is generally acquired during childhood with no symptoms but has
      long- term clinical sequelae. This study estimated the prevalence of H. pylori
      infection amongst children in a rural environment in Africa. METHODS: We
      conducted a cross-sectional study over a four (4)-month period within two rural
      communities. 240 asymptomatic children were tested using lateral flow
      immunochromatographic assay for the qualitative detection of H. pylori antigen in
      a fecal specimen. Statistical analysis and processing was done using Stata
      version 11. RESULTS: The mean age of the participants was 10.5 +/- 2.7 years with
      the predominant age range being 8-10 years (34.6%), and a mean household size of
      7.1 +/- 1.7. The study population showed a female preponderance of 57.1%. 88% of
      the H. pylori positive children lacked pipe and borehole drinking water. All of
      the positive H. pylori children practiced open-air defecation. The overall
      prevalence of H. pylori infection among children in this study was at least
      14.2%. CONCLUSION: Our study demonstrated a high prevalence of H. pylori
      infection among children in a rural setting. Educational status of parents did
      not affect H. pylori prevalence but increasing household numbers, female gender,
      source of drinking water other than pipe and borehole, open-air defecation and
      younger age were associated with a higher H. pylori prevalence.

PMID- 28438159
TI  - Prevalence of Plasmodium falciparum and non-P. falciparum infections in a
      highland district in Ghana, and the influence of HIV and sickle cell disease.
AB  - BACKGROUND: In the past two decades, there has been a reported decline in malaria
      in Ghana and the rest of the world; yet it remains the number one cause of
      mortality and morbidity. Human immuno-deficiency virus (HIV) and sickle cell
      disease (SCD) share a common geographical space with malaria in sub-Saharan
      Africa and an interaction between these three conditions has been suggested. This
      study determined the Plasmodium falciparum and non-P. falciparum status of
      symptomatic and non-symptomatic residents of Mpraeso in the highlands of Kwahu
      South district of Ghana based on evidence of current national decline. The
      influence of HIV and SCD on malaria was also determined. METHODS: Participants
      were 354 symptomatic patients visiting the Kwahu Government Hospital and 360
      asymptomatic residents of the district capital. This cross-sectional study was
      conducted during the minor rainy season (October-December 2014). Rapid diagnostic
      tests (RDT), blood film microscopy and real-time polymerase chain reaction
      assessment of blood were done. Participants who tested positive with RDT were
      treated with artemisinin-based combination therapy; and assessment of venous
      blood was repeated 7 days after treatment. HIV screening and haemoglobin
      genotyping was done. Univariate and multivariate regression analysis was used to
      determine the influence of SCD and HIV. RESULTS: Plasmodium falciparum was
      prevalent at 124/142 (87.3%). Plasmodium malariae was the only non-falciparum
      species detected at 18/142 (12.7%). HIV and SCD did not significantly increase
      odds of malaria infection. However, the use of ITN and recent anti-malarial
      intake significantly decreased the odds of being malaria infected by 0.45-fold
      and 0.46-fold respectively. CONCLUSION: Plasmodium falciparum and P. malariae
      infection are the prevailing species in the study area; albeit varying from the
      national average. HIV and SCD were not associated with the risk of having
      malaria.

PMID- 28438160
TI  - Use of oral health care services in Finnish adults - results from the cross
      sectional Health 2000 and 2011 Surveys.
AB  - BACKGROUND: During the 2000s, two major legislative reforms concerning oral
      health care have been implemented in Finland. One entitled the whole population
      to subsidized care and the other regulated the timeframes of access to care. Our
      aim was, in a cross-sectional setting, to assess changes in and determinants of
      use of oral health care services before the first reform in 2000 and after both
      reforms in 2011. METHODS: The data were part of the nationally representative
      Health 2000 and 2011 Surveys of adults aged >= 30 years and were gathered by
      interviews and questionnaires. The outcome was the use of oral health care
      services during the previous year. Determinants of use among the dentate were
      grouped according to Andersen's model: predisposing (sex, age group), enabling
      (education, recall, dental fear, habitual use of services, household income,
      barriers of access to care), and need (perceived need, self-rated oral health,
      denture status). Chi square tests and logistic regression analyses were used for
      statistical evaluation. RESULTS: No major changes or only a minor increase in
      overall use of oral health care services was seen between the study years. An
      exception were those belonging to oldest age group who clearly increased their
      use of services. Also, a significant increase in visiting a public sector dentist
      was observed, particularly in the age groups that became entitled to subsidized
      care in 2000. In the private sector, use of services decreased in younger age
      groups. Determinants for visiting a dentist, regardless of the service sector,
      remained relatively stable. Being a regular dental visitor was the most
      significant determinant for having visited a dentist during the previous year.
      Enabling factors, both organizational and individual, were emphasized. They
      seemed to enable service utilization particularly in the private sector.
      CONCLUSIONS: Overall changes in the use of oral health care services were
      relatively small, but in line with the goals set for the reform. Older persons
      increased use of services in both sectors, implying growing need. Differences
      between public and private sectors persisted, and recall, costs of care and
      socioeconomic factors steered choices between the sectors, sustaining inequity in
      access to care.

PMID- 28438161
TI  - REFOLDdb: a new and sustainable gateway to experimental protocols for protein
      refolding.
AB  - BACKGROUND: More than 7000 papers related to "protein refolding" have been
      published to date, with approximately 300 reports each year during the last
      decade. Whilst some of these papers provide experimental protocols for protein
      refolding, a survey in the structural life science communities showed a necessity
      for a comprehensive database for refolding techniques. We therefore have
      developed a new resource - "REFOLDdb" that collects refolding techniques into a
      single, searchable repository to help researchers develop refolding protocols for
      proteins of interest. RESULTS: We based our resource on the existing REFOLD
      database, which has not been updated since 2009. We redesigned the data format to
      be more concise, allowing consistent representations among data entries compared
      with the original REFOLD database. The remodeled data architecture enhances the
      search efficiency and improves the sustainability of the database. After an
      exhaustive literature search we added experimental refolding protocols from
      reports published 2009 to early 2017. In addition to this new data, we fully
      converted and integrated existing REFOLD data into our new resource. REFOLDdb
      contains 1877 entries as of March 17th, 2017, and is freely available at
      http://p4d-info.nig.ac.jp/refolddb/ . CONCLUSION: REFOLDdb is a unique database
      for the life sciences research community, providing annotated information for
      designing new refolding protocols and customizing existing methodologies. We
      envisage that this resource will find wide utility across broad disciplines that
      rely on the production of pure, active, recombinant proteins. Furthermore, the
      database also provides a useful overview of the recent trends and statistics in
      refolding technology development.

PMID- 28438162
TI  - Targeting of nicotinamide phosphoribosyltransferase enzymatic activity
      ameliorates lung damage induced by ischemia/reperfusion in rats.
AB  - BACKGROUND: Emerging evidence reveals that nicotinamide phosphoribosyltransferase
      (NAMPT) has a significant role in the pathophysiology of the inflammatory
      process. NAMPT inhibition has a beneficial effect in the treatment of a variety
      of inflammatory diseases. However, it remains unclear whether NAMPT inhibition
      has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this
      study, we examined whether NAMPT inhibition provided protection against I/R lung
      injury in rats. METHODS: Isolated perfused rat lungs were subjected to 40 min of
      ischemia followed by 60 min of reperfusion. The rats were randomly allotted to
      the control, control + FK866 (NAMPT inhibitor, 10 mg/kg), I/R, or I/R + FK866
      groups (n = 6 per group). The effects of FK866 on human alveolar epithelial cells
      exposed to hypoxia-reoxygenation (H/R) were also investigated. RESULTS: Treatment
      with FK866 significantly attenuated the increases in lung edema, pulmonary
      arterial pressure, lung injury scores, and TNF-alpha, CINC-1, and IL-6
      concentrations in bronchoalveolar lavage fluid in the I/R group. Malondialdehyde
      levels, carbonyl contents and MPO-positive cells in lung tissue were also
      significantly reduced by FK866. Additionally, FK866 mitigated I/R-stimulated
      degradation of IkappaB-alpha, nuclear translocation of NF-kappaB, Akt
      phosphorylation, activation of mitogen-activated protein kinase, and
      downregulated MKP-1 activity in the injured lung tissue. Furthermore, FK866
      increased Bcl-2 and decreased caspase-3 activity in the I/R rat lungs.
      Comparably, the in vitro experiments showed that FK866 also inhibited IL-8
      production and NF-kappaB activation in human alveolar epithelial cells exposed to
      H/R. CONCLUSIONS: Our findings suggest that NAMPT inhibition may be a novel
      therapeutic approach for I/R-induced lung injury. The protective effects involve
      the suppression of multiple signal pathways.

PMID- 28438163
TI  - Enhanced status of inflammation and endothelial activation in subjects with
      familial hypercholesterolaemia and their related unaffected family members: a
      case control study.
AB  - BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary
      artery diseases (CAD) which pathophysiologically can be measured by inflammation,
      endothelial activation and oxidative stress status. However, the status of these
      biomarkers among related unaffected relatives of FH cases and whether FH is an
      independent predictor of these biomarkers have not been well established. Thus,
      this study aims to (1) compare the biomarkers of inflammation, endothelial
      activation and oxidative stress between patients with FH, their related
      unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether
      FH is an independent predictor of these biomarkers. METHODS: One hundred thirty
      one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile,
      biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E
      selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and
      F2-isoprostanes (ISP)] were analyzed and independent predictor was determined
      using binary logistic regression analysis. RESULTS: hsCRP was higher in FH and
      RUC compared to NC (mean +/- SD = 1.53 +/- 1.24 mg/L and mean +/- SD = 2.54 +/-
      2.30 vs 1.10 +/- 0.89 mg/L, p < 0.05). sICAM-1 and E-selectin were higher in FH
      compared to NC (mean +/- SD = 947 +/- 742 vs 655 +/- 191 ng/mL, p < 0.001 and 175
      +/- 131 vs 21.6 +/- 10.7 ng/mL, p < 0.001 respectively) while sICAM-1
      concentration was higher in RUC compared to NC (mean +/- SD = 945 +/- 379 vs 655
      +/- 191 ng/mL, p < 0.01). Biomarkers of oxidation (ox-LDL, MDA and ISP) were
      elevated in FH compared to NC [mean +/- SD = (48.2 +/- 26.8 vs 27.3 +/- 13.2
      mU/L, p < 0.001), (2.57 +/- 1.3 vs 1.20 +/- 0.30 nmol/mL, p < 0.001) and (645 +/-
      396 vs 398 +/- 20.5 pg/L, p < 0.001) respectively], but no significant
      differences were observed between RUC and NC (p > 0.05). FH was an independent
      predictor for sICAM-1 (p = 0.007), ox-LDL (p < 0.001) and MDA (p < 0.001) while
      RUC independently predicted for sICAM-1 (p < 0.001). CONCLUSION: The screening
      for FH is vital as all biomarkers associated with atherogenesis are higher in
      these subjects and FH also independently predict biomarkers of endothelial
      activation and oxidative stress. Furthermore, despite not fulfilling the
      diagnostic criteria for FH, related unaffected family members that may not
      phenotypically express the mutation may still be at risk of developing CAD as
      reflected from the enhanced inflammatory and endothelial activation status
      observed in this group. This highlights the need to not only conduct family
      tracing in indexed FH cases, but also assess the coronary risk among family
      members that do not fulfil the FH diagnostic criteria.

PMID- 28438164
TI  - Aggregation/dispersion transitions of T4 phage triggered by environmental ion
      availability.
AB  - BACKGROUND: Bacteriophage survives in at least two extremes of ionic
      environments: bacterial host (high ionic-cytosol) and that of soil (low ionic
      environmental water). The impact of ionic composition in the micro- and macro
      environments has not so far been addressed in phage biology. RESULTS: Here, we
      discovered a novel mechanism of aggregation/disaggregation transitions by phage
      virions. When normal sodium levels in phage media (150 mM) were lowered to 10 mM,
      advanced imaging by scanning electron microscopy, atomic force microscopy and
      dynamic light scattering all revealed formation of viral packages, each
      containing 20-100 virions. When ionic strength was returned from low to high, the
      aggregated state of phage reversed to a dispersed state, and the change in ionic
      strength did not substantially affect infectivity of the phage. By providing the
      direct evidence, that lowering of the sodium ion below the threshold of 20 mM
      causes rapid aggregation of phage while returning Na+ concentration to the values
      above this threshold causes dispersion of phage, we identified a biophysical
      mechanism of phage aggregation. CONCLUSIONS: Our results implicate operation of
      group behavior in phage and suggest a new kind of quorum sensing among its
      virions that is mediated by ions. Loss of ionic strength may act as a trigger in
      an evolutionary mechanism to improve the survival of bacteriophage by stimulating
      aggregation of phage when outside a bacterial host. Reversal of phage aggregation
      is also a promising breakthrough in biotechnological applications, since we
      demonstrated here the ability to retain viable virion aggregates on standard
      micro-filters.

PMID- 28438165
TI  - Microglia-derived IL-1beta promotes chemokine expression by Muller cells and RPE
      in focal retinal degeneration.
AB  - BACKGROUND: Chemokine signalling is required for the homing of leukocytes during
      retinal inflammation, and is associated with pathogenesis of diseases such as age
      related macular degeneration (AMD). Here, we explore the role of interleukin
      1beta (IL-1beta) in modulating AMD-associated chemokines Ccl2, Cxcl1, and Cxcl10
      during photo-oxidative retinal damage, and the effect on both the accumulation of
      outer-retinal macrophages, and death of photoreceptors. METHODS: Inhibition of
      retinal IL-1beta expression was performed using either siRNA or antibody
      neutralisation, which was intravitreally injected in SD rats prior to photo
      oxidative damage. Changes in the expression and localisation of Il-1beta, Ccl2,
      Cxcl1 and Cxcl10 genes were assessed using qPCR and in situ hybridisation, while
      the recruitment of retinal macrophages was detected using immunohistochemistry
      for IBA1. Levels of photoreceptor cell death were determined using TUNEL.
      RESULTS: Photo-oxidative damage elevated the expression of Il-1beta and
      inflammasome-related genes, and IL-1beta protein was detected in microglia
      infiltrating the outer retina. This was associated with increased expression of
      Ccl2, Cxcl1, and Cxcl10. Intravitreal IL-1beta inhibitors suppressed chemokine
      expression following damage and reduced macrophage accumulation and photoreceptor
      death. Moreover, in Muller and RPE cell cultures, and in vivo, Ccl2, Cxcl1 and
      Cxcl10 were variously upregulated when stimulated with IL-1beta, with increased
      macrophage accumulation detected in vivo. CONCLUSIONS: IL-1beta is produced by
      retinal microglia and macrophages and promotes chemokine expression by Muller
      cells and RPE in retinal degeneration. Targeting IL-1beta may prove efficacious
      in broadly suppressing chemokine-mediated inflammation in retinal dystrophies
      such as AMD.

PMID- 28438166
TI  - Adjacent regenerative peripheral nerve interfaces produce phase-antagonist
      signals during voluntary walking in rats.
AB  - BACKGROUND: Regenerative Peripheral Nerve Interfaces (RPNIs) are neurotized
      muscle grafts intended to produce electromyographic signals suitable for
      motorized prosthesis control. Two RPNIs producing independent agonist/antagonist
      signals are required for each control axis; however, it is unknown whether
      signals from adjacent RPNIs are independent. The purpose of this work was to
      determine signaling characteristics from two adjacent RPNIs, the first neurotized
      by a foot dorsi-flexor nerve and the second neurotized by a foot plantar-flexor
      nerve in a rodent model. METHODS: Two Control group rats had electrodes implanted
      onto the soleus (tibial nerve) and extensor digitorum longus (peroneal nerve)
      muscles in the left hind limb. Two Dual-RPNI group rats had two separate muscles
      grafted to the left thigh and each implanted with electrodes: the extensor
      digitorum longus was neurotized with a transected fascicle from the tibial nerve,
      and the tibialis anterior was implanted with a transected peroneal nerve. Four
      months post-surgery, rats walked on a treadmill, were videographed, and
      electromyographic signals were recorded. Amplitude and periodicity of all signals
      relative to gait period were quantified. To facilitate comparisons across groups,
      electromyographic signals were expressed as a percent of total stepping cycle
      activity for each stance and swing gait phase. Independence between peroneal and
      tibial nerve activations were assessed by statistical comparisons between groups
      during stance and swing. RESULTS: Electromyographic activity for Control and Dual
      RPNI rats displayed alternating activation patterns coinciding with stance and
      swing. Significant signal amplitude differences between the peroneal and tibial
      nerves were found in both the Control and Dual-RPNI groups. Non-inferiority tests
      performed on Dual-RPNI group signal confidence intervals showed that activation
      was equivalent to the Control group in all but the peroneal RPNI construct during
      stance. The similar electromyographic activity obtained for Control and RPNI
      suggests the latter constructs activate independently during both stance and
      swing, and contain minimal crosstalk. CONCLUSIONS: In-vivo myoelectric RPNI
      activity encodes neural activation patterns associated with gait. Adjacent RPNIs
      neurotized with agonist/antagonist nerves display activity amplitudes similar to
      Control during voluntary walking. The distinct and expected activation patterns
      indicate the RPNI may provide independent signaling in humans, suitable for
      motorized prosthesis control.

PMID- 28438167
TI  - Dependency criterion based brain pathological age estimation of Alzheimer's
      disease patients with MR scans.
AB  - OBJECTIVES: Traditional brain age estimation methods are based on the idea that
      uses the real age as the training label. However, these methods ignore that there
      is a deviation between the real age and the brain age due to the accelerated
      brain aging. METHODS: This paper considers this deviation and obtains it by
      maximizing the correlation between the estimated brain age and the class label
      rather than by minimizing the difference between the estimated brain age and the
      real age. Firstly, set the search range of the deviation as the deviation
      candidates according to the prior knowledge. Secondly, use the support vector
      regression as the age estimation model to minimize the difference between the
      estimated age and the real age plus deviation rather than the real age itself.
      Thirdly, design the fitness function based on the correlation criterion.
      Fourthly, conduct age estimation on the validation dataset using the trained age
      estimation model, put the estimated age into the fitness function, and obtain the
      fitness value of the deviation candidate. Fifthly, repeat the iteration until all
      the deviation candidates are involved and get the optimal deviation with maximum
      fitness values. The real age plus the optimal deviation is taken as the brain
      pathological age. RESULTS: The experimental results showed that the separability
      of the samples was apparently improved. For normal control- Alzheimer's disease
      (NC-AD), normal control- mild cognition impairment (NC-MCI), and mild cognition
      impairment-Alzheimer's disease (MCI-AD), the average improvements were 0.164
      (31.66%), 0.1284 (34.29%), and 0.0206 (7.1%), respectively. For NC-MCI-AD, the
      average improvement was 0.2002 (50.39%). The estimated brain pathological age
      could be not only more helpful for the classification of AD but also more
      precisely reflect the accelerated brain aging. CONCLUSION: In conclusion, this
      paper proposes a new kind of brain age-brain pathological age and offers an
      estimation method for it that can distinguish different states of AD, thereby
      better reflecting accelerated brain aging. Besides, the brain pathological age is
      most helpful for feature reduction, thereby simplifying the relevant
      classification algorithm.

PMID- 28438168
TI  - Upon entering an age of global ivermectin-based integrated mass drug
      administration for neglected tropical diseases and malaria.
AB  - Ivermectin mass drug administration (MDA) in humans to reduce malaria vectors is
      yet another use for this remarkable medicine whose discoverers shared the 2015
      Nobel Prize in Medicine with the discoverer of artemisinin. The malaria community
      should join those who have long used ivermectin MDA in an integrated battle to
      break transmission of three vector-borne parasitic diseases.

PMID- 28438169
TI  - Ivermectin and malaria control.
AB  - As the world begins to realize the very real prospect of eliminating malaria as a
      public health problem globally, the scientific community is acutely aware that
      novel and innovative new tools will be required if that lofty goal is to be
      accomplished. Moreover, the need for comprehensive, integrated products and
      interventions is being recognized in order for the critical 'final steps' toward
      elimination to be taken successfully. Failure to take these crucial last steps
      have dogged all past global disease elimination programmes, except for smallpox.
      The success of ivermectin in driving two of the most devastating and disfiguring
      neglected tropical diseases (NTD) to the brink of elimination has been well
      documented. The drug also bestows immeasurable non-target benefits, increasing
      the health and socioeconomic prospects of all communities where mass drug
      administration (MDA) has been carried out. Ivermectin kills a variety of
      parasites and insects, including the Anopheline vectors of malaria parasites. In
      view of long-standing MDA programmes, increasing attention is now being paid to
      the potential offered by re-formulating and re-purposing ivermectin to function
      as a feed-though mosquitocidal tool. This will provide a comprehensively
      beneficial weapon, for the anti-malarial armamentarium, as well as for probably
      improving the impact on existing target diseases. Prospects currently look highly
      promising, especially as the drug is already proven to be extremely safe for
      human use. However, for maximum impact, detailed analysis of various analogues of
      the unique ivermectin, as well as the parent avermectin compounds, will need to
      be undertaken. 'Ivermectin' comprises an imprecise mix of two compounds, both of
      which are potent anthelmintics. Yet recently, it has been confirmed that only the
      minor of the two component compounds is molluscicidal. Further structure activity
      relationship studies may well identify the analogue, analogues or combination
      thereof best suited for use in a concerted initiative to simultaneously tackle
      malaria and other NTD in poly-parasitized communities.

PMID- 28438170
TI  - Immunolocalization of steroidogenic enzymes in the vaginal mucous of Galea spixii
      during the estrous cycle.
AB  - BACKGROUND: The synthesis of sex steroids is controlled by several enzymes such
      as17alpha-hydroxylase cytochrome P450 (P450c17) catalyzing androgen synthesis and
      aromatase cytochrome P450 (P450arom) catalyzing estrogen synthesis, both of which
      must complex with the redox partner NADPH-cytochrome P450 oxidoreductase (CPR)
      for activity. Previous studies have identified expression of steroidogenic
      enzymes in vaginal tissue, suggesting local sex steroid synthesis. The current
      studies investigate P450c17, P450aromatase and CPR expression in vaginal mucosa
      of Galea spixii (Spix cavy) by immuno-histochemical and western immunoblot
      analyses. METHODS: Stages of estrous cyclicity were monitored by vaginal
      exfoliative cytology. After euthanasia, vaginal tissues were retrieved, fixed and
      frozen at diestrus, proestrus, estrus and metestrus. The ovaries and testis were
      used as positive control tissues for immunohistochemistry. RESULTS: Data from
      cytological study allowed identification of different estrous cycle phases.
      Immunohistochemical analysis showed different sites of expression of
      steroidogenic enzymes along with tissue response throughout different phases of
      the estrous cycle. However, further studies are needed to characterize the
      derived hormones synthesized by, and the enzymes activities associated with,
      vaginal tissues. CONCLUSION: Current results not only support the expression of
      enzymes involved in sex steroid synthesis in the wall of the vagina, they also
      indicate that expression changes with the stage of the cycle, both the levels and
      types of cells exhibiting expression. Thus, changes in proliferation of vaginal
      epithelial cells and the differentiation of the mucosa may be influenced by local
      steroid synthesis as well as circulating androgens and estrogens.

PMID- 28438172
TI  - Erratum to: Riverine fishers' knowledge of extreme climatic events in the
      Brazilian Amazonia.

PMID- 28438171
TI  - A systematic review and meta-analysis of moderate-to-vigorous physical activity
      levels in secondary school physical education lessons.
AB  - BACKGROUND: Schools play an important role in physical activity promotion for
      adolescents. The systematic review aimed to determine the proportion of secondary
      (middle and high) school physical education (PE) lesson time that students spend
      in moderate to vigorous physical activity (MVPA), and to assess if MVPA was
      moderated by school level (middle and high school), type of physical activity
      measurement and type of PE activities. METHODS: A systematic search of nine
      electronic databases was conducted (PROSPERO2014:CRD42014009649). Studies were
      eligible if they were published between 2005 and 2014; written in English;
      assessed MVPA in PE lessons of secondary (middle and high) school students; and
      used a quantitative MVPA measure (i.e., accelerometry, heart rate monitoring,
      pedometers or observational measures). Two reviewers examined the retrieved
      articles, assessed risk of bias, and performed data extraction. Random effects
      meta-analysis was used to calculate a pooled estimate of the percent of PE lesson
      time spent in MVPA and to assess moderator effects where data allowed. RESULTS:
      The search yielded 5,132 potentially relevant articles; 28 articles representing
      25 studies (7 middle and 18 high school) from seven countries were included.
      Twelve studies measured MVPA through observational measures, seven used
      accelerometers, five used heart rate monitors and four used pedometers (including
      three studies using a mix of measures). Meta-analysis of 15 studies found that
      overall, students spent a mean (95% CI) of 40.5% (34.8-46.2%) of PE in MVPA.
      Middle school students spent 48.6% (41.3-55.9%) of the lesson in MVPA (n = 5
      studies) and high school students 35.9% (28.3-43.6%) (n = 10 studies). Studies
      measuring MVPA using accelerometers (n = 5) showed that students spent 34.7%
      (25.1-44.4%) of the lesson in MVPA, while 44.4% (38.3-50.5%) was found for
      lessons assessed via observation (n = 9), 43.1% (24.3-61.9%) of the lesson for a
      heart rate based study, and 35.9% (31.0-40.8%) for a pedometer-measured study.
      CONCLUSIONS: The proportion of PE spent in MVPA (40.5%) is below the US Centre
      for Disease Control and Prevention and the UK Associations for Physical Education
      recommendation of 50%. Findings differed according to the method of MVPA
      assessment. Additional strategies and intervention research are needed to build
      more active lesson time in PE.

PMID- 28438173
TI  - Preliminary results demonstrating the impact of Mediterranean diet on bone
      health.
AB  - BACKGROUND: Nutrition is an environmental factor affecting bone health. Nutrition
      is considered essential to achieve and maintain optimal bone mass. Mediterranean
      diet (MD) has shown to prevent bone disease. Aim of this study is to investigate
      the relationship between bone health status and adherence the MD. METHODS: Four
      hundred eighteen healthy people (105 males and 313 females, age 50 +/- 14 years)
      were recruited in the outdoor hospital of the "Campus Salute Onlus" held in
      Piazza del Plebiscito in Naples, October 17-20th 2013 and 09-11th October 2014.
      All subjects underwent clinical assessment, calcaneal quantitative ultrasound
      (QUS) scanner and PREvencion con DIeta MEDiterranea (PREDIMED) questionnaire.
      RESULTS: Globally, prevalence of osteoporosis and osteopenia were 7.7 and 46.0%,
      respectively. The majority of subjects (60.5%) had an average score (score 6-9)
      of adherence to MD. The T-score showed positive correlation with PREDIMED score
      (r = 0.250, p < 0.001). The higher T-scores were positively associated with a
      higher consumption of extra-virgin olive oil (EVOO), vegetables, fruits, legumes,
      and fish and negatively associated with consumption of red meat. The higher T
      scores were positively associated with the highest odds of PREDIMED scores
      (higher adherence) (OR 6.91, IC 6.27-7.61, p < 0.001). Multiple regression
      analysis models indicated that, among the single food items investigated, high T
      score can be predicted by consumption of EVOO (p < 0.001), fish (p < 0.001) and
      fruit (p = 0.002) intake. A PREDIMED score of 3 was found to be predictive for a
      low T-score (alpha = 0.05, R-squared index = 0.417). CONCLUSIONS: The results
      demonstrate a positive correlation between bone health status and adherence to
      MD, suggesting that a high adherence to MD promotes bone health. The observations
      here reported confirmed that a specific dietary approach, such as MD, can
      represent a modifiable environmental factor for osteoporosis' prevention.

PMID- 28438174
TI  - Exercise attenuates neurological deficits by stimulating a critical HSP70/NF
      kappaB/IL-6/synapsin I axis in traumatic brain injury rats.
AB  - BACKGROUND: Despite previous evidence for a potent inflammatory response after a
      traumatic brain injury (TBI), it is unknown whether exercise preconditioning (EP)
      improves outcomes after a TBI by modulating inflammatory responses. METHODS: We
      performed quantitative real-time PCR (qPCR) to quantify the genes encoding 84
      cytokines and chemokines in the peripheral blood and used ELISA to determine both
      the cerebral and blood levels of interleukin-6 (IL-6). We also performed the
      chromatin immunoprecipitation (ChIP) assay to evaluate the extent of nuclear
      factor kappa-B (NF-kappaB) binding to the DNA elements in the IL-6 promoter
      regions. Also, we adopted the Western blotting assay to measure the cerebral
      levels of heat shock protein (HSP) 70, synapsin I, and beta-actin. Finally, we
      performed both histoimmunological and behavioral assessment to measure brain
      injury and neurological deficits, respectively. RESULTS: We first demonstrated
      that TBI upregulated nine pro-inflammatory and/or neurodegenerative messenger
      RNAs (mRNAs) in the peripheral blood such as CXCL10, IL-18, IL-16, Cd-70, Mif,
      Ppbp, Ltd, Tnfrsf 11b, and Faslg. In addition to causing neurological injuries,
      TBI also upregulated the following 14 anti-inflammatory and/or neuroregenerative
      mRNAs in the peripheral blood such as Ccl19, Ccl3, Cxcl19, IL-10, IL-22, IL-6,
      Bmp6, Ccl22, IL-7, Bmp7, Ccl2, Ccl17, IL-1rn, and Gpi. Second, we observed that
      EP inhibited both neurological injuries and six pro-inflammatory and/or
      neurodegenerative genes (Cxcl10, IL-18, IL-16, Cd70, Mif, and Faslg) but
      potentiated four anti-inflammatory and/or neuroregenerative genes (Bmp6, IL-10,
      IL-22, and IL-6). Prior depletion of cerebral HSP70 with gene silence
      significantly reversed the beneficial effects of EP in reducing neurological
      injuries and altered gene profiles after a TBI. A positive Pearson correlation
      exists between IL-6 and HSP70 in the peripheral blood or in the cerebral levels.
      In addition, gene silence of cerebral HSP70 significantly reduced the
      overexpression of NF-kappaB, IL-6, and synapsin I in the ipsilateral brain
      regions after an EP in rats. CONCLUSIONS: TBI causes neurological deficits
      associated with stimulating several pro-inflammatory gene profiles but inhibiting
      several anti-inflammatory gene profiles of cytokines and chemokines. Exercise
      protects against neurological injuries via stimulating an anti-inflammatory
      HSP70/NF-kappaB/IL-6/synapsin I axis in the injured brains.

PMID- 28438175
TI  - A matched-pair analysis comparing whole-brain radiotherapy with and without a
      stereotactic boost for intracerebral control and overall survival in patients
      with one to three cerebral metastases.
AB  - BACKGROUND: Twelve years ago, a randomized trial demonstrated that a radiosurgery
      boost added to whole-brain radiotherapy (WBRT) improved intracerebral control
      (IC) in patients with one to three cerebral metastases. Overall survival (OS) was
      improved only in the subgroup of patients with a single metastasis but not in the
      entire cohort. The present study compared both regimens in a different scenario
      outside a randomized trial. METHODS: A total of 252 patients with one to three
      cerebral metastases were included. Eighty-four patients receiving WBRT plus a
      planned stereotactic boost and 168 patients receiving WBRT alone were
      individually matched 1:2 for nine factors including fractionation of WBRT, age,
      gender, performance score, primary tumor, number of cerebral metastases,
      extracerebral metastases, recursive partitioning analysis class, and time between
      cancer diagnosis and WBRT. Each group of three patients was required to match for
      all nine factors. Both groups were compared for IC and OS. RESULTS: IC rates at
      6, 12, 18 and 24 months were 88, 71, 45 and 22% after WBRT plus stereotactic
      boost vs. 75, 48, 38 and 22% after WBRT alone (p = 0.005). OS rates at 6, 12, 18
      and 24 months were 76, 53, 32 and 25% after WBRT plus stereotactic boost and 67,
      45, 29 and 20% after WBRT alone (p = 0.10). In patients with a single lesion, OS
      rates were also not significantly different (p = 0.12). CONCLUSIONS: Similar to
      the previous randomized trial from 2004, this matched-pair study showed that a
      stereotactic boost in addition to WBRT significantly improved IC but not OS.

PMID- 28438177
TI  - Responding to non-communicable diseases in Zambia: a policy analysis.
AB  - BACKGROUND: Non-communicable diseases (NCDs) are an emerging global health
      concern. Reports have shown that, in Zambia, NCDs are also an emerging problem
      and the government has begun initiating a policy response. The present study
      explores the policy response to NCDs by the Ministry of Health in Zambia using
      the policy triangle framework of Walt and Gilson. METHODS: A qualitative approach
      was used for the study. Data collected through key informant interviews with
      stakeholders who were involved in the NCD health policy development process as
      well as review of key planning and policy documents were analysed using thematic
      analysis. RESULTS: The government's policy response was as a result of
      international strategies from WHO, evidence of increasing disease burden from
      NCDs and pressure from interest groups. The government developed the NCD
      strategic plan based on the WHO Global Action Plan for NCDs 2013-2030.
      Development of the NCD strategic plan was driven by the government through the
      Ministry of Health, who set the agenda and adopted the final document.
      Stakeholders participated in the fine tuning of the draft document from the
      Ministry of Health. The policy development process was lengthy and this affected
      consistency in composition of the stakeholders and policy development momentum.
      Lack of representative research evidence for some prioritised NCDs and use of
      generic targets and indicators resulted in the NCD strategic plan being
      inadequate for the Zambian context. The interventions in the strategic plan also
      underutilised the potential of preventing NCDs through health education. Recent
      government pronouncements were also seen to be conflicting the risk factor
      reduction strategies outlined in the NCD strategic plan. CONCLUSION: The content
      of the NCD strategic plan inadequately covered all the major NCDs in Zambia.
      Although contextual factors like international strategies and commitments are
      crucial catalysts to policy development, there is need for domestication of
      international guidelines and frameworks to match the disease burden, resources
      and capacities in the local context if policy measures are to be comprehensive,
      relevant and measurable. Such domestication should be guided by representative
      local research evidence.

PMID- 28438176
TI  - The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase
      activity.
AB  - BACKGROUND: Mutations in PINK1 and PARKIN are the most common causes of recessive
      early-onset Parkinson's disease (EOPD). Together, the mitochondrial ubiquitin
      (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex
      regulated, sequential mitochondrial quality control. Thereby, damaged
      mitochondria are identified and targeted to degradation in order to prevent their
      accumulation and eventually cell death. Homozygous or compound heterozygous loss
      of either gene function disrupts this protective pathway, though at different
      steps and by distinct mechanisms. While structure and function of PARKIN variants
      have been well studied, PINK1 mutations remain poorly characterized, in
      particular under endogenous conditions. A better understanding of the exact
      molecular pathogenic mechanisms underlying the pathogenicity is crucial for
      rational drug design in the future. METHODS: Here, we characterized the
      pathogenicity of the PINK1 p.I368N mutation on the clinical and genetic as well
      as on the structural and functional level in patients' fibroblasts and in cell
      based, biochemical assays. RESULTS: Under endogenous conditions, PINK1 p.I368N is
      expressed, imported, and N-terminally processed in healthy mitochondria similar
      to PINK1 wild type (WT). Upon mitochondrial damage, however, full-length PINK1
      p.I368N is not sufficiently stabilized on the outer mitochondrial membrane (OMM)
      resulting in loss of mitochondrial quality control. We found that binding of
      PINK1 p.I368N to the co-chaperone complex HSP90/CDC37 is reduced and stress
      induced interaction with TOM40 of the mitochondrial protein import machinery is
      abolished. Analysis of a structural PINK1 p.I368N model additionally suggested
      impairments of Ub kinase activity as the ATP-binding pocket was found deformed
      and the substrate Ub was slightly misaligned within the active site of the
      kinase. Functional assays confirmed the lack of Ub kinase activity. CONCLUSIONS:
      Here we demonstrated that mutant PINK1 p.I368N can not be stabilized on the OMM
      upon mitochondrial stress and due to conformational changes in the active site
      does not exert kinase activity towards Ub. In patients' fibroblasts, biochemical
      assays and by structural analyses, we unraveled two pathomechanisms that lead to
      loss of function upon mutation of p.I368N and highlight potential strategies for
      future drug development.

PMID- 28438178
TI  - Automatic construction of statistical shape models using deformable simplex
      meshes with vector field convolution energy.
AB  - BACKGROUND: In the active shape model framework, principal component analysis
      (PCA) based statistical shape models (SSMs) are widely employed to incorporate
      high-level a priori shape knowledge of the structure to be segmented to achieve
      robustness. A crucial component of building SSMs is to establish shape
      correspondence between all training shapes, which is a very challenging task,
      especially in three dimensions. METHODS: We propose a novel mesh-to-volume
      registration based shape correspondence establishment method to improve the
      accuracy and reduce the computational cost. Specifically, we present a greedy
      algorithm based deformable simplex mesh that uses vector field convolution as the
      external energy. Furthermore, we develop an automatic shape initialization method
      by using a Gaussian mixture model based registration algorithm, to derive an
      initial shape that has high overlap with the object of interest, such that the
      deformable models can then evolve more locally. We apply the proposed deformable
      surface model to the application of femur statistical shape model construction to
      illustrate its accuracy and efficiency. RESULTS: Extensive experiments on ten
      femur CT scans show that the quality of the constructed femur shape models via
      the proposed method is much better than that of the classical spherical harmonics
      (SPHARM) method. Moreover, the proposed method achieves much higher computational
      efficiency than the SPHARM method. CONCLUSIONS: The experimental results suggest
      that our method can be employed for effective statistical shape model
      construction.

PMID- 28438179
TI  - Genome adaptive evolution of Lactobacillus casei under long-term antibiotic
      selection pressures.
AB  - BACKGROUND: The extensive use of antibiotics in medicine has raised serious
      concerns about biosafety. However, the effect of antibiotic application on the
      adaptive evolution of microorganisms, especially to probiotic bacteria, has not
      been well characterized. Thus, the objective of the current work was to
      investigate how antibiotic selection forces might drive genome adaptation using
      Lactobacillus (L.) casei Zhang as a model. METHODS: Two antibiotics, amoxicillin
      and gentamicin, were consistently applied to the laboratory culture of L. casei
      Zhang. We then monitored the mutations in the bacterial genome and changes in the
      minimum inhibitory concentrations (MICs) of these two antibiotics along a 2000
      generation-cultivation lasted over 10 months. RESULTS: We found an approximately
      4-fold increase in the genome mutation frequency of L. casei Zhang, i.e. 3.5 * 10
      9 per base pair per generation under either amoxicillin or gentamicin stress,
      when compared with the parallel controls grown without application of any
      antibiotics. The increase in mutation frequency is significantly lower than that
      previously reported in Escherichia (E.) coli. The rate of de novo mutations, i.e.
      20 per genome, remained low and stable throughout the long-term cultivation.
      Moreover, the accumulation of new mutations stopped shortly after the maximum
      bacterial fitness (i.e. the antibiotic MICs) was reached. CONCLUSIONS: Our study
      has shown that the probiotic species, L. casei Zhang, has high genome stability
      even in the presence of long-term antibiotic stresses. However, whether this is a
      species-specific or universal characteristic for all probiotic bacteria remains
      to be explored.

PMID- 28438181
TI  - Efficient vitrification of mouse embryos using the Kitasato Vitrification System
      as a novel vitrification device.
AB  - BACKGROUND: Currently, the cryopreservation of embryos and oocytes is essential
      for assisted reproductive technology (ART) laboratories worldwide. This study
      aimed to evaluate the efficacy of the Kitasato Vitrification System (KVS) as a
      vitrification device for the cryopreservation of mouse embryos to determine
      whether this novel device can be adapted to the field of ART. METHODS: In
      Experiment 1, blastocysts were vitrified using the KVS. Vitrified blastocysts
      were warmed and subsequently cultured for 72 h. In Experiment 2, 2-cell-stage
      embryos were vitrified using the KVS, and vitrified embryos were warmed and
      subsequently cultured for 96 h. In Experiment 3, we evaluated the in vivo
      developmental potential of vitrified 2-cell-stage embryos using the KVS, and in
      Experiment 4, we evaluated the cooling and warming rates for these devices using
      a numerical simulation. RESULTS: In Experiment 1, there were no significant
      differences between the survival rates of the KVS and a control device. However,
      re-expanded (100%) and hatching (91.8%) rates were significantly higher for
      blastocysts vitrified using the KVS. In Experiment 2, there were no significant
      differences between the survival rates, or rates of development to the blastocyst
      stage, of vitrified and fresh embryos. In Experiment 3, after embryo transfer,
      41% of the embryos developed into live offspring. In Experiment 4, the cooling
      and warming rates of the KVS were 683,000 and 612,000  degrees C/min,
      respectively, exceeding those of the control device. CONCLUSIONS: Our study
      clearly demonstrates that the KVS is a novel vitrification device for the
      cryopreservation of mouse embryos at the blastocyst and 2-cell stage.

PMID- 28438180
TI  - Recent advances of highly selective CDK4/6 inhibitors in breast cancer.
AB  - Uncontrolled cell division is the hallmark of cancers. Full understanding of cell
      cycle regulation would contribute to promising cancer therapies. In particular,
      cyclin-dependent kinases 4/6 (CDK4/6), which are pivotal drivers of cell
      proliferation by combination with cyclin D, draw more and more attention.
      Subsequently, extensive studies were carried out to explore drugs inhibiting
      CDK4/6 and assess the efficacy and safety of these drugs in cancer, especially
      breast cancer. Due to the insuperable adverse events and the less activity
      observed in vivo, the drug development of the initial pan-CDK inhibitor
      flavopiridol was consequently discontinued, and then highly specific inhibitors
      were extensively researched and developed, including palbociclib (PD0332991),
      ribociclib (LEE011), and abemaciclib (LY2835219). Food and Drug Administration
      has approved palbociclib and ribociclib for the treatment of hormone receptor
      positive, human epidermal growth factor receptor 2-negative advanced or
      metastatic breast cancer, and recent clinical trial data suggest that palbociclib
      significantly improved clinical outcome when combined with letrozole or
      fulvestrant. Besides, the favorable effects of abemaciclib on prolonging survival
      of breast cancer patients have also been observed in clinical trials both for
      single-agent and combination strategy. In this review, we outline the preclinical
      and clinical advancement of these three orally bioavailable and highly selective
      CDK4/6 inhibitors in breast cancer.

PMID- 28438182
TI  - Forced fluid removal versus usual care in intensive care patients with high-risk
      acute kidney injury and severe fluid overload (FFAKI): study protocol for a
      randomised controlled pilot trial.
AB  - BACKGROUND: Intravenous administration of fluids is an essential part of critical
      care. While some fluid administration is likely beneficial, there is increasing
      observational evidence that the development of fluid overload is associated with
      increased mortality. There are no randomised trials to confirm this association
      in patients with acute kidney injury. We aim to perform a pilot trial to test the
      feasibility of forced fluid removal compared to standard care in patients with
      acute kidney injury and severe fluid overload, the FFAKI trial. METHODS: Then
      FFAKI trial is a pilot, multicentre, randomised clinical trial recruiting adult
      intensive care patients with acute kidney injury and fluid overload, defined as
      more than 10% of ideal bodyweight. Patients are randomised with concealed
      allocation to either standard care or forced fluid removal with a therapeutic
      target of negative net fluid balance >=1 mL/kg/h. The safety of fluid removal is
      continually evaluated according to predefined criteria of hypoperfusion: lactate
      >=4 mmol/L, mean arterial pressure <50 mmHg or mottling beyond the edge of the
      kneecaps. If patients fulfil one of these criteria, fluid removal is suspended
      until hypoperfusion has resolved. The primary outcome measure is fluid balance at
      5 days after randomisation and secondary outcomes include mean daily fluid
      balance, fluid balance at discharge from the intensive care unit, time to neutral
      fluid balance, number of serious adverse reactions and number of protocol
      violations. All patients are followed for 90 days. DISCUSSION: The FFAKI trial
      started in October 2015 and, when completed, will provide data to evaluate
      whether a large trial of forced fluid removal in critically ill patients is
      feasible. Our primary outcome will show if the experimental intervention leads to
      a clinically relevant difference in fluid balance, which could prove beneficial
      in intensive care patients with acute kidney injury. TRIAL REGISTRATION: EudraCT,
      identifier: 2015-001701-13. Registered on 19 September 2015; ClinicalTrials.gov,
      identifier: NCT02458157 . Registered on 21 May 2015; Danish Ethics Committee,
      identifier: H-15009589H. Registered on 22 September 2015; Danish Health and
      Medicines Authority, identifier: 2015070013. Registered on 11 August 2015.

PMID- 28438183
TI  - Semaphorin-Plexin signaling influences early ventral telencephalic development
      and thalamocortical axon guidance.
AB  - BACKGROUND: Sensory processing relies on projections from the thalamus to the
      neocortex being established during development. Information from different
      sensory modalities reaching the thalamus is segregated into specialized nuclei,
      whose neurons then send inputs to cognate cortical areas through topographically
      defined axonal connections. Developing thalamocortical axons (TCAs) normally
      approach the cortex by extending through the subpallium; here, axonal navigation
      is aided by distributed guidance cues and discrete cell populations, such as the
      corridor neurons and the internal capsule (IC) guidepost cells. In mice lacking
      Semaphorin-6A, axons from the dorsal lateral geniculate nucleus (dLGN) bypass the
      IC and extend aberrantly in the ventral subpallium. The functions normally
      mediated by Semaphorin-6A in this system remain unknown, but might depend on
      interactions with Plexin-A2 and Plexin-A4, which have been implicated in other
      neurodevelopmental processes. METHODS: We performed immunohistochemical and
      neuroanatomical analyses of thalamocortical wiring and subpallial development in
      Sema6a and Plxna2; Plxna4 null mutant mice and analyzed the expression of these
      genes in relevant structures. RESULTS: In Plxna2; Plxna4 double mutants we
      discovered TCA pathfinding defects that mirrored those observed in Sema6a
      mutants, suggesting that Semaphorin-6A - Plexin-A2/Plexin-A4 signaling might
      mediate dLGN axon guidance at subpallial level. In order to understand where and
      when Semaphorin-6A, Plexin-A2 and Plexin-A4 may be required for proper subpallial
      TCA guidance, we then characterized their spatiotemporal expression dynamics
      during early TCA development. We observed that the thalamic neurons whose axons
      are misrouted in these mutants normally express Semaphorin-6A but not Plexin-A2
      or Plexin-A4. By contrast, all three proteins are expressed in corridor cells and
      other structures in the developing basal ganglia. This finding could be
      consistent with an hypothetical action of Plexins as guidance signals through
      Sema6A as a receptor on dLGN axons, and/or with their indirect effect on TCA
      guidance due to functions in the morphogenesis of subpallial intermediate
      targets. In support of the latter possibility, we observed that in both Plxna2;
      Plxna4 and Sema6a mutants some IC guidepost cells abnormally localize in
      correspondence of the ventral path misrouted TCAs elongate into. CONCLUSIONS:
      These findings implicate Semaphorin-6A - Plexin-A2/Plexin-A4 interactions in dLGN
      axon guidance and in the spatiotemporal organization of guidepost cell
      populations in the mammalian subpallium.

PMID- 28438184
TI  - Microbiota-activated CD103+ DCs stemming from microbiota adaptation specifically
      drive gammadeltaT17 proliferation and activation.
AB  - BACKGROUND: IL-17-producing gammadeltaT cells (gammadeltaT17) promote
      autoinflammatory diseases and cancers. Yet, gammadeltaT17 peripheral regulation
      has not been thoroughly explored especially in the context of microbiota-host
      interaction. The potent antigen-presenting CD103+ dendritic cell (DC) is a key
      immune player in close contact with both gammadeltaT17 cells and microbiota. This
      study presents a novel cellular network among microbiota, CD103+ DCs, and
      gammadeltaT17 cells. METHODS: Immunophenotyping of IL-17r-/- mice and IL-17r-/-
      IRF8-/- mice were performed by ex vivo immunostaining and flow cytometric
      analysis. We observed striking microbiome differences in the oral cavity and gut
      of IL-17r-/- mice by sequencing 16S rRNA gene (v1-v3 region) and analyzed using
      QIIME 1.9.0 software platform. Principal coordinate analysis of unweighted
      UniFrac distance matrix showed differential clustering for WT and IL-17r-/- mice.
      RESULTS: We found drastic homeostatic expansion of gammadeltaT17 in all major
      tissues, most prominently in cervical lymph nodes (cLNs) with monoclonal
      expansion of Vgamma6 gammadeltaT17 in IL-17r-/- mice. Ki-67 staining and in vitro
      CFSE assays showed cellular proliferation due to cell-to-cell contact stimulation
      with microbiota-activated CD103+ DCs. A newly developed double knockout mice
      model for IL-17r and CD103+ DCs (IL-17r-/-IRF8-/-) showed a specific reduction in
      Vgamma6 gammadeltaT17. Vgamma6 gammadeltaT17 expansion is inhibited in germ-free
      mice and antibiotic-treated specific pathogen-free (SPF) mice. Microbiota
      transfer using cohousing of IL-17r-/- mice with wildtype mice induces
      gammadeltaT17 expansion in the wildtype mice with increased activated CD103+ DCs
      in cLNs. However, microbiota transfer using fecal transplant through oral gavage
      to bypass the oral cavity showed no difference in colon or systemic gammadeltaT17
      expansion. CONCLUSIONS: These findings reveal for the first time that
      gammadeltaT17 cells are regulated by microbiota dysbiosis through cell-to-cell
      contact with activated CD103+ DCs leading to drastic systemic, monoclonal
      expansion. Microbiota dysbiosis, as indicated by drastic bacterial population
      changes at the phylum and genus levels especially in the oral cavity, was
      discovered in mice lacking IL-17r. This network could be very important in
      regulating both microbiota and immune players. This critical regulatory pathway
      for gammadeltaT17 could play a major role in IL-17-driven inflammatory diseases
      and needs further investigation to determine specific targets for future
      therapeutic intervention.

PMID- 28438185
TI  - Comparison of the efficacy between conventional moxibustion and smoke-free
      moxibustion on knee osteoarthritis: study protocol of a randomized controlled
      trial.
AB  - BACKGROUND: Conventional moxibustion is a representative non-drug intervention in
      traditional Chinese medicine, and it has been reported to produce encouraging
      results and benefits in relieving symptoms and improving the quality of life for
      patients with knee osteoarthritis (KOA) in previous clinical trials and
      systematic reviews. Given that increasing concerns on the safety of generated
      smoke from conventional moxibustion have received much attention, smoke-free
      moxibustion is regarded as a potential alternative. However, whether smoke-free
      moxibustion would display a similar efficacy to that of conventional moxibustion
      still remains unclear. Therefore, this randomized controlled trial attempts to
      investigate the difference of efficacy between conventional moxibustion and smoke
      free moxibustion in patients with KOA. METHODS/DESIGN: This is a multicenter,
      randomized, single-blinded, parallel-group clinical trial. A total of 138
      eligible participants with KOA will be randomly allocated to two groups
      (conventional moxibustion group and smoke-free moxibustion group) in seven
      hospitals in China. Participants will receive 12 sessions of moxibustion
      treatment at three acupoints (EX-LE4, ST35, and ST36) over a period of 4 weeks (3
      sessions per week). A smoke-removing device is placed at the top of the
      moxibustion device for the smoke-free moxibustion group (n = 69), while the
      conventional moxibustion group (n = 69) is treated with traditional moxibustion.
      The primary outcome measure will be the change of the global scale of the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from the baseline
      to 4 weeks. Secondary outcomes include the visual analog scale VASand Patient
      Global Assessment scores. Follow-up measurements will be performed on the 8th and
      12th weeks after random allocation. DISCUSSION: This study will contribute to
      providing a solid foundation for the selection of moxibustion in clinical
      application as well as future research in moxibustion therapy. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02772055 . Registered on 12 May 2016.

PMID- 28438186
TI  - MOrtality and infectious complications of therapeutic EndoVAscular interventional
      radiology: a systematic and meta-analysis protocol.
AB  - BACKGROUND: Endovascular interventional radiology (EIR) is an increasingly
      popular, mini invasive treatment option for patient with symptomatic vascular
      disease. The EIR practiced by qualified hands is an effective, well-tolerated
      procedure that offers relief of patient's symptoms with a low risk of
      complications. During acute post procedural period, immediate complications may
      relate to vascular access, restenosis, thromboembolic events, uterine ischemia,
      infection, necrosis, sepsis, ICU stay, surgical recovery, pain management,
      treatment failure, and death. Moreover, additional non-life-threatening
      complications exist, but they are not well described and represent disparate
      information. METHODS/DESIGN: A range of databases will be screened consulted to
      identify the relevant studies: PubMed, EMBASE, The Cochrane Library, NosoBase,
      and Google Scholar (to identify articles not yet indexed). Scientist librarian
      used Medical Subject Headings (MeSH) and free terms to construct the search
      strategy in PubMed. This search strategy will be adapted in other databases. Two
      coauthors will independently select the relevant studies, extract the relevant
      data, and assess the risk of bias in the included studies. Any disagreements
      between the two authors will be solved by a third author. DISCUSSION: This
      systematic review will provide a synthesis of EIR complications. The spotlighted
      results will be analyzed in order to provide a state-of-knowledge synopsis of the
      current evidence base in relation to the epidemiology of the infectious
      complications after EIR. In the event of conclusive results, our findings will
      serve as a reference background to assess guidelines on reality of the problem of
      the infections linked to endovascular interventional radiology and to formulate
      of assumptions and propose preventive measures, based on the results of our
      investigations. These propositions will aim to reduce the risk and/or the
      severity of these complications in the concerned population in favor a positive
      medical economics report. It will also aim to decrease the antibio-resistance and
      in fine will improve health status and security of patients. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42015025594.

PMID- 28438187
TI  - Prevention of cervical cancer in HIV-seropositive women from developing
      countries: a systematic review protocol.
AB  - BACKGROUND: Over 85% of cervical cancer cases and deaths occur in developing
      countries. HIV-seropositive women are more likely to develop precancerous lesions
      that lead to cervical cancer than HIV-negative women. However, the literature on
      cervical cancer prevention in seropositive women in developing countries has not
      been reviewed. The aim of this study is to systematically review cervical cancer
      prevention modalities available for HIV-seropositive women in developing
      countries. METHODS/DESIGN: This protocol was developed by following the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P)
      statement, and the systematic review will be reported in accordance with the
      PRISMA guidelines. Embase, MEDLINE, PubMed, CINAHL and Cochrane Library will be
      searched from inception up to date of final search, and additional studies will
      be located through citation and reference list tracking. Eligible studies will be
      randomised controlled trials, prospective and retrospective cohort studies, case
      control and cross-sectional studies carried out in developing countries. Studies
      will be included if they are published in English and examine cervical cancer
      prevention modalities in HIV-seropositive women. Results will be summarised in
      tables and, where appropriate, combined using meta-analysis. DISCUSSION: This
      review will address the gap in evidence by systematically reviewing the published
      literature on the different prevention modalities being used to prevent cervical
      cancer in HIV-seropositive women in developing countries. The findings may be
      used to inform evidence-based guidelines for prevention of cervical cancer in
      seropositive women as well as future research. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42017054678 .

PMID- 28438189
TI  - Modulated evaluation metrics for drug-based ontologies.
AB  - BACKGROUND: Research for ontology evaluation is scarce. If biomedical ontological
      datasets and knowledgebases are to be widely used, there needs to be quality
      control and evaluation for the content and structure of the ontology. This paper
      introduces how to effectively utilize a semiotic-inspired approach to ontology
      evaluation, specifically towards drug-related ontologies hosted on the National
      Center for Biomedical Ontology BioPortal. RESULTS: Using the semiotic-based
      evaluation framework for drug-based ontologies, we adjusted the quality metrics
      based on the semiotic features of drug ontologies. Then, we compared the quality
      scores before and after tailoring. The scores revealed a more precise measurement
      and a closer distribution compared to the before-tailoring. CONCLUSION: The
      results of this study reveal that a tailored semiotic evaluation produced a more
      meaningful and accurate assessment of drug-based ontologies, lending to the
      possible usefulness of semiotics in ontology evaluation.

PMID- 28438188
TI  - Luteinizing hormone elevation in ovarian granulosa cell tumor: a case report and
      review of the literature.
AB  - BACKGROUND: Ovarian granulosa cell tumors (GCTs) are the most common type of
      potentially malignant ovarian sex cord-stromal tumor. GCTs often produce estrogen
      and/or progesterone; consequently, symptoms related to hyperestrogenism are
      common at diagnosis. Nonspecific symptoms or signs associated with this neoplasm
      include amenorrhea and changes in various sex hormone levels, which can be hard
      to diagnose or explain. The aims of this report were to describe a case of GCT
      with rare presentations and to review the pertinent literature. CASE
      PRESENTATION: A 33-year-old woman presented with secondary amenorrhea and
      elevated LH with normal FSH and low estradiol levels. Laparoscopy revealed an
      ovarian GCT, and the patient underwent left adnexectomy and platinum-based
      chemotherapy. Removal of the ovarian GCT resulted in the normalization of LH
      levels and a return to spontaneous menses. CONCLUSIONS: The mechanisms
      responsible for elevations in serum LH due to GCTs require further investigation.
      However, addressing the patient's clinical problems remains the most important
      treatment consideration.

PMID- 28438190
TI  - Very small embryonic-like stem cells (VSELs) in adult mouse uterine perimetrium
      and myometrium.
AB  - We have earlier reported the presence of very small embryonic-like stem cells
      (VSELs) in adult mouse uterus along with slightly bigger progenitors termed
      endometrial stem cells (EnSCs) and their regulation by ovarian hormones thus
      demonstrating a crucial role played by them during proliferation, differentiation
      and remodeling of the endometrium. Present study is a brief communication wherein
      we have examined the effect of higher dose of estrogen (E, 2 MUg/day),
      progesterone (P, 1 mg/day) and follicle stimulating hormone (FSH, 5 IU/day for 5
      days) specifically on the myometrium and perimetrium surrounding the endometrium
      in bilaterally ovariectomized mice. Similar treatment with E & P was recently
      used in a study published in the journal Nature to study the effect of steroid
      hormones on hematopoietic stem cells and this treatment regimen helps achieve
      hormone levels observed during pregnancy. Quiescent spherical stem cells (lacking
      PCNA expression) with high nucleo-cytoplasmic ratio and nuclear OCT-4A were
      detected in the perimetrium of atrophied (bilaterally ovariectomized) uterus.
      PCNA expression was observed after treatment and cells with cytoplasmic OCT-4B
      were invariably observed in the myometrium. VSELs were clearly visualized after
      treatment and the effect of P and FSH was more prominent compared to E on the
      development of myometrium. It is speculated that stem cells with nuclear OCT-4A
      located in the perimetrium differentiate to give rise to endothelial and
      myometrial cells with cytoplasmic OCT-4B. Based on the results of present study
      and published reports showing the presence of pluripotent markers (OCT-4, NANOG
      and SOX2) in human myometrial side population and expression of particularly OCT
      4A in human leiomyomas, we speculate that these nuclear OCT-4 positive stem cells
      located in the perimetrium are the possible tumor initiating cells leading to the
      development of leiomyomas rather than the mesenchymal cells which express
      cytoplasmic OCT-4B.

PMID- 28438191
TI  - Continuous diphenhydramine infusion and imatinib for KIT-D816V-negative mast cell
      activation syndrome: a case report.
AB  - BACKGROUND: We present the first full case report of the treatment of mast cell
      activation syndrome with continuous diphenhydramine infusion, which resulted in
      the improvement of anaphylactic reactions and a decrease in hospital readmission.
      Furthermore, the patient received imatinib in the absence of the KIT-D816V
      mutation, which led to further improvement of quality of life. Currently, we are
      trying to wean this patient off diphenhydramine; if successful, this attempt will
      represent the first reported case. CASE PRESENTATION: An 18-year-old white girl
      presented with a flare of mast cell activation syndrome and received epinephrine
      and steroids. She had failed multiple previous therapies, and her quality of life
      was affected due to two to three flares/week. She was started on continuous
      diphenhydramine infusion and imatinib, which led to a decrease in hospital
      admissions and marked improvement in her quality of life. CONCLUSIONS: Continuous
      diphenhydramine infusion can provide promising outcomes following the failure of
      intermittent antihistamine dosing in patients with severe mast cell activation
      syndrome. Initiating continuous diphenhydramine infusion may be helpful in an
      intensive care setting when the patient is particularly prone to anaphylaxis
      and/or the resources needed to manage anaphylaxis are not available outside the
      intensive care unit. Furthermore, imatinib provides benefits in KIT-D816V
      negative mast cell disorders due to other unknown mutations.

PMID- 28438192
TI  - Chryseobacterium gleum in a man with prostatectomy in Senegal: a case report and
      review of the literature.
AB  - BACKGROUND: Here we report a rare case of a urinary tract infection due to
      Chryseobacterium gleum. This widely distributed Gram-negative bacillus is an
      uncommon human pathogen and is typically associated with health care settings.
      CASE PRESENTATION: We describe a case of urinary tract infection caused by
      Chryseobacterium gleum in a 68-year-old man of Wolof ethnicity (an ethnic group
      in Senegal, West Africa) who presented to our Department of Urology in a
      university teaching hospital (Hopital Aristide Le Dantec) in Dakar, Senegal, 1
      month after prostatectomy. The strain isolated from a urine sample was identified
      as Chryseobacterium gleum by mass spectrometry (Vitek matrix-assisted laser
      desorption/ionization, time-of-flight, bioMerieux) and confirmed by 16S ribosomal
      ribonucleic acid sequencing. The organism was resistant to a wide range of
      antibiotics, including carbapenem, due to a resident metallo-beta-lactamase gene
      that shared 99% of amino-acid identity with Chryseobacterium gleum class B enzym.
      CONCLUSIONS: Infection by Chryseobacterium gleum is infrequent, and no such case
      has been previously reported in Africa. Despite its low virulence,
      Chryseobacterium gleum should be considered a potential opportunistic and
      emerging pathogen. Further studies on the epidemiology, pathogenicity, and
      resistance mechanisms of Chryseobacterium gleum are needed for better diagnosis
      and management.

PMID- 28438193
TI  - PathOS: a decision support system for reporting high throughput sequencing of
      cancers in clinical diagnostic laboratories.
AB  - BACKGROUND: The increasing affordability of DNA sequencing has allowed it to be
      widely deployed in pathology laboratories. However, this has exposed many issues
      with the analysis and reporting of variants for clinical diagnostic use.
      Implementing a high-throughput sequencing (NGS) clinical reporting system
      requires a diverse combination of capabilities, statistical methods to identify
      variants, global variant databases, a validated bioinformatics pipeline, an
      auditable laboratory workflow, reproducible clinical assays and quality control
      monitoring throughout. These capabilities must be packaged in software that
      integrates the disparate components into a useable system. RESULTS: To meet these
      needs, we developed a web-based application, PathOS, which takes variant data
      from a patient sample through to a clinical report. PathOS has been used
      operationally in the Peter MacCallum Cancer Centre for two years for the
      analysis, curation and reporting of genetic tests for cancer patients, as well as
      the curation of large-scale research studies. PathOS has also been deployed in
      cloud environments allowing multiple institutions to use separate, secure and
      customisable instances of the system. Increasingly, the bottleneck of variant
      curation is limiting the adoption of clinical sequencing for molecular
      diagnostics. PathOS is focused on providing clinical variant curators and
      pathology laboratories with a decision support system needed for personalised
      medicine. While the genesis of PathOS has been within cancer molecular
      diagnostics, the system is applicable to NGS clinical reporting generally.
      CONCLUSIONS: The widespread availability of genomic sequencers has highlighted
      the limited availability of software to support clinical decision-making in
      molecular pathology. PathOS is a system that has been developed and refined in a
      hospital laboratory context to meet the needs of clinical diagnostics. The
      software is available as a set of Docker images and source code at
      https://github.com/PapenfussLab/PathOS .

PMID- 28438194
TI  - Malaria profiles and challenges in artemisinin resistance containment in Myanmar.
AB  - BACKGROUND: This study examined evolving malaria profiles from January, 2010 to
      December, 2014 to evaluate achievements and challenges of implementing measures
      to prevent and control spread of artemisinin resistance in Myanmar. METHODS:
      Using National Malaria Control Programme (NMCP) data, a cross-sectional
      descriptive study of 52 townships in artemisinin-resistant containment areas in
      Myanmar was conducted. Annual program data were analysed, and trends over time
      are graphically presented. RESULTS: In the 52 study townships populated by 8.7
      million inhabitants, malaria incidence showed a decreasing trend from 10.54 per 1
      000 population in 2010 to 2.53 in 2014, and malaria mortalities also decreased
      from 1.83 per 100 000 population in 2010 to 0.17 in 2014. The proportion of
      confirmed to total tested malaria cases also decreased from 6 to 1%, while
      identification of cases improved. All cases from all parasites species, including
      Plasmodium falciparum, decreased. Coverage of LLIN (long-lasting insecticidal
      net)/ITN (insecticide-treated mosquito nets) and indoor residual spraying (IRS)
      was high in targeted areas with at-risk persons, even though the total population
      was not covered. In addition to passive case detection (PCD), active case
      detection (ACD) was conducted in hard-to-reach areas and worksites where mobile
      migrant populations were present. ACD improved in most areas from 2012 to 2014,
      but continues to need to be strengthened. CONCLUSIONS: The findings provide
      useful data on the malaria situation in artemisinin-resistant initiative areas,
      which may be useful for the NMCP to meet its elimination goal. These profiles
      could contribute to better planning, implementation, and evaluation of
      intervention activities.

PMID- 28438195
TI  - Delivery of alcohol brief interventions in community-based youth work settings:
      exploring feasibility and acceptability in a qualitative study.
AB  - BACKGROUND: Alcohol Brief Interventions (ABIs) are increasingly being delivered
      in community-based youth work settings. However, little attention has been paid
      to how they are being implemented in such settings, or to their feasibility and
      acceptability for practitioners or young people. The aim of this qualitative
      study was to explore the context, feasibility and acceptability of ABI delivery
      in youth work projects across Scotland. METHODS: Individual, paired and group
      interviews were conducted with practitioners and young people in nine community
      projects that were either involved in the delivery of ABIs or were considering
      doing so in the near future. A thematic analysis approach was used to analyse
      data. RESULTS: ABIs were delivered in a diverse range of youth work settings
      including the side of football pitches, on the streets as part of outreach
      activities, and in sexual health drop-in centres for young people. ABI delivery
      differed in a number of important ways from delivery in other health settings
      such as primary care, particularly in being largely opportunistic and flexible in
      nature. ABIs were adapted by staff in line with the ethos of their project and
      their own roles, and to avoid jeopardising their relationships with young people.
      Young people reacted positively to the idea of having conversations about alcohol
      with youth project workers, but confirmed practitioners' views about the
      importance of these conversations taking place in the context of an existing
      trusting relationship. CONCLUSION: ABIs were feasible in a range of youth work
      settings with some adaptation. Acceptability to staff was strongly influenced by
      perceived benefits, and the extent to which ABIs fitted with their project's
      ethos. Young people were largely comfortable with such conversations. Future
      implementation efforts should be based on detailed consideration of current
      practice and contexts. Flexible models of delivery, where professional judgement
      can be exercised over defined but adaptable content, may be better appreciated by
      staff and encourage further development of ABI activity.

PMID- 28438196
TI  - Examiner effect on the objective structured clinical exam - a study at five
      medical schools.
AB  - BACKGROUND: The Objective Structured Clinical Examination (OSCE) is increasingly
      used at medical schools to assess practical competencies. To compare the outcomes
      of students at different medical schools, we introduced standardized OSCE
      stations with identical checklists. METHODS: We investigated examiner bias at
      standardized OSCE stations for knee- and shoulder-joint examinations, which were
      implemented into the surgical OSCE at five different medical schools. The
      checklists for the assessment consisted of part A for knowledge and performance
      of the skill and part B for communication and interaction with the patient. At
      each medical faculty, one reference examiner also scored independently to the
      local examiner. The scores from both examiners were compared and analysed for
      inter-rater reliability and correlation with the level of clinical experience.
      Possible gender bias was also evaluated. RESULTS: In part A of the checklist,
      local examiners graded students higher compared to the reference examiner; in
      part B of the checklist, there was no trend to the findings. The inter-rater
      reliability was weak, and the scoring correlated only weakly with the examiner's
      level of experience. Female examiners rated generally higher, but male examiners
      scored significantly higher if the examinee was female. CONCLUSIONS: These
      findings of examiner effects, even in standardized situations, may influence
      outcome even when students perform equally well. Examiners need to be made aware
      of these biases prior to examining.

PMID- 28438198
TI  - Health related quality of life in Dutch infants, toddlers, and young children.
AB  - BACKGROUND: The purpose of this study is to provide Dutch normative data and to
      assess internal consistency and known-groups validity for the TNO AZL Preschool
      Children Quality of Life (TAPQOL) and the acute version of the generic Pediatric
      Quality of Life Inventory (PedsQL 4.0) in Dutch young children aged 0-7 years.
      METHODS: Participants were selected from a panel of a large Dutch market research
      agency. A sample of 794 parents (response rate 61%, 39% fathers) of children (53%
      boys) from the general Dutch population, completed an electronic version of the
      TAPQOL (N = 227 infants aged 0-1 years) or PedsQL 4.0 (N = 293 toddlers aged 2-4
      years and N = 274 young children aged 5-7 years). RESULTS: Except for the
      'stomach' scale (alpha = .39), the TAPQOL showed acceptable to excellent internal
      consistency (alpha = .60-.88). The PedsQL 4.0 showed acceptable to excellent
      reliability in children aged 2-4 years (alpha = .60-.88) and in children aged 5-7
      years (alpha = .76-.90). Children with a chronic health condition had lower
      scores than healthy children on 3 out of 12 domains of the TAPQOL (p = .001-.013)
      and on 2 out of 6 domains of the PedsQL 4.0 for children aged 2-4 years (p = .016
      .04). The PedsQL 4.0 differentiated on all domains (p < .05) between children
      aged 5-7 years with and without a chronic health condition. CONCLUSION: In Dutch
      children aged 0-7 years old, HRQoL can be relialy measured with the TAPQOL and
      the PedsQL 4.0. However, it remains unclear whether these HRQoL instruments can
      distinguish between healthy children and children with a chronic health condition
      under the age of 5.

PMID- 28438197
TI  - Anti-malarial landscape in Myanmar: results from a nationally representative
      survey among community health workers and the private sector outlets in
      2015/2016.
AB  - BACKGROUND: In 2015/2016, an ACTwatch outlet survey was implemented to assess the
      anti-malarial and malaria testing landscape in Myanmar across four domains
      (Eastern, Central, Coastal, Western regions). Indicators provide an important
      benchmark to guide Myanmar's new National Strategic Plan to eliminate malaria by
      2030. METHODS: This was a cross-sectional survey, which employed stratified
      cluster-random sampling across four regions in Myanmar. A census of community
      health workers (CHWs) and private outlets with potential to distribute malaria
      testing and/or treatment was conducted. An audit was completed for all anti
      malarials, malaria rapid diagnostic tests. RESULTS: A total of 28,664 outlets
      were approached and 4416 met the screening criteria. The anti-malarial market
      composition comprised CHWs (41.5%), general retailers (27.9%), itinerant drug
      vendors (11.8%), pharmacies (10.9%), and private for-profit facilities (7.9%).
      Availability of different anti-malarials and diagnostic testing among anti
      malarial-stocking CHWs was as follows: artemisinin-based combination therapy
      (ACT) (81.3%), chloroquine (67.0%), confirmatory malaria test (77.7%). Less than
      half of the anti-malarial-stocking private sector had first-line treatment in
      stock: ACT (41.7%) chloroquine (41.8%), and malaria diagnostic testing was rare
      (15.4%). Oral artemisinin monotherapy (AMT) was available in 27.7% of private
      sector outlets (Western, 54.1%; Central, 31.4%; Eastern; 25.0%, Coastal; 15.4%).
      The private-sector anti-malarial market share comprised ACT (44.0%), chloroquine
      (26.6%), and oral AMT (19.6%). Among CHW the market share was ACT (71.6%),
      chloroquine (22.3%); oral AMT (3.8%). More than half of CHWs could correctly
      state the national first-line treatment for uncomplicated falciparum and vivax
      malaria (59.2 and 56.9%, respectively) compared to the private sector (15.8 and
      13.2%, respectively). Indicators on support and engagement were as follows for
      CHWs: reportedly received training on malaria diagnosis (60.7%) or national
      malaria treatment guidelines (59.6%), received a supervisory or regulatory visit
      within 12 months (39.1%), kept records on number of patients tested or treated
      for malaria (77.3%). These indicators were less than 20% across the private
      sector. CONCLUSION: CHWs have a strong foundation for achieving malaria goals and
      their scale-up is merited, however gaps in malaria commodities and supplies must
      be addressed. Intensified private sector strategies are urgently needed and must
      be scaled up to improve access and coverage of first-line treatments and malaria
      diagnosis, and remove oral AMT from the market place. Future policies and
      interventions on malaria control and elimination in Myanmar should take these
      findings into consideration across all phases of implementation.

PMID- 28438199
TI  - Risk of low birth weight on adulthood hypertension - evidence from a tertiary
      care hospital in a South Asian country, Sri Lanka: a retrospective cohort study.
AB  - BACKGROUND: Although low birth weight (LBW) is common in South Asian region there
      are not many studies being done to evaluate LBW and adulthood hypertension
      association in this region, including in Sri Lanka. Although this association has
      been studied in other regions, most studies have not evaluated this association
      in the presence of socioeconomic and lifestyle factors. This study was conducted
      to investigate whether low birth weight (LBW) is associated with adulthood
      hypertension after adjusting for other potential risk factors of hypertension.
      METHODS: Nearly 15,000 individuals born during 1950 to 1965 were selected and
      invitations were sent to their original addresses. Out of them 217 individuals
      responded and among them birth weight was recovered for 122 individuals. Separate
      linear logistic models were fitted to model high systolic blood pressure (SBP:
      systolic blood pressure > 140 mmHg), high diastolic blood pressure (DBP:
      diastolic blood pressure > 90 mmHg) and hypertension (either SBP > 140 mmHg or
      DBP > 90 mmHg). RESULTS: Separate linear logistic model fitting revealed LBW
      having a significant association with high SBP (OR = 2.89; 95% CI: 1.01 to 8.25;
      P = 0.04), and hypertension (OR = 3.15; 95% CI: 1.17 to 9.35; P = 0.03), but not
      with high DBP (OR = 0.75; 95% CI: 0.22 to 2.16; P = 0.62), when effect of LBW was
      studied after adjusting for all other potential risk factors. CONCLUSIONS: LBW
      has a tendency to cause high adult blood pressure in South Asian region, and the
      findings are consistent with previous work on LBW and adulthood hypertension
      association in other regions of the world.

PMID- 28438200
TI  - A novel strategy to improve protein secretion via overexpression of the SppA
      signal peptide peptidase in Bacillus licheniformis.
AB  - BACKGROUND: Signal peptide peptidases play an important role in the removal of
      remnant signal peptides in the cell membrane, a critical step for extracellular
      protein production. Although these proteins are likely a central component for
      extracellular protein production, there has been a lack of research on whether
      protein secretion could be enhanced via overexpression of signal peptide
      peptidases. RESULTS: In this study, both nattokinase and alpha-amylase were
      employed as prototypical secreted target proteins to evaluate the function of
      putative signal peptide peptidases (SppA and TepA) in Bacillus licheniformis. We
      observed dramatic decreases in the concentrations of both target proteins (45 and
      49%, respectively) in a sppA deficient strain, while the extracellular protein
      yields of nattokinase and alpha-amylase were increased by 30 and 67% respectively
      in a strain overexpressing SppA. In addition, biomass, specific enzyme activities
      and the relative gene transcriptional levels were also enhanced due to the
      overexpression of sppA, while altering the expression levels of tepA had no
      effect on the concentrations of the secreted target proteins. CONCLUSIONS: Our
      results confirm that SppA, but not TepA, plays an important functional role for
      protein secretion in B. licheniformis. Our results indicate that the sppA
      overexpression strain, B. licheniformis BL10GS, could be used as a promising host
      strain for the industrial production of heterologous secreted proteins.

PMID- 28438201
TI  - Relation of antioxidant status at admission and disease severity and outcome in
      dogs naturally infected with Babesia canis canis.
AB  - BACKGROUND: Canine babesiosis is caused by species of the Babesia genus and has
      become an emerging disease worldwide. To the authors' knowledge there are no
      reports in which antioxidants have been analyzed in different presentations of
      canine babesiosis or in which the prognostic value of antioxidants has been
      studied. The aim of this study was to evaluate whether oxidative stress could be
      related to the severity and outcome of canine babesiosis. For this purpose a
      profile consisting of four antioxidant biomarkers (superoxide dismutase - SOD,
      glutathione peroxidase - GPx, catalase, total antioxidant status - TAS) and
      malondialdehyde - MDA as an oxidant biomarker (previously evaluated, here studied
      for comparative purposes) were evaluated in dogs with canine babesiosis of
      different clinical severity and outcomes. RESULTS: The study was conducted with a
      sample of 40 dogs suffering from babesiosis (further divided into uncomplicated,
      one complication and multiple organ dysfunction syndrome - MODS group) and 30
      healthy dogs (control group). Additionally, the babesiosis group was divided
      according to the anaemia into non-anaemic, mildly anaemic, moderately anaemic and
      severely anaemic dogs. The results of our study showed significantly decreased
      SOD, catalase and TAS values in diseased dogs compared to controls, while there
      were no significant differences in GPx between these groups. Dogs that developed
      MODS showed lower activities of SOD and GPx and higher MDA values compared to
      dogs with uncomplicated babesiosis as well as with dogs that developed one
      complication. Superoxide dismutase, catalase and GPx were negatively correlated
      whereas MDA was positively correlated with the lethal outcome of the disease.
      Furthermore, this study detected more pronounced decrease in antioxidant
      biomarkers (SOD, GPx and catalase) in dogs with moderate anaemia compared to
      those with mild anaemia. CONCLUSIONS: The results of this study showed changes in
      biomarkers related to the antioxidant status of dogs naturally infected with B.
      canis canis. These biomarkers could be used as indicators of disease severity and
      outcome in dogs suffering from babesiosis.

PMID- 28438202
TI  - Does parental and adolescent participation in an e-health lifestyle modification
      intervention improves weight outcomes?
AB  - BACKGROUND: Few studies have evaluated the effect of adherence to a lifestyle
      intervention on adolescent health outcomes. The objective of this study was to
      determine whether adolescent and parental adherence to components of an e-health
      intervention resulted in change in adolescent body mass index (BMI) and waist
      circumference (WC) z-scores in a sample of overweight/obese adolescents. METHODS:
      In total, 159 overweight/obese adolescents and their parents participated in an 8
      month e-health lifestyle intervention. Each week, adolescents and their parents
      were asked to login to their respective website and to monitor their dietary,
      physical activity, and sedentary behaviours. We examined participation
      (percentage of webpages viewed [adolescents]; number of weeks logged in
      [parents]) and self-monitoring (number of weeks behaviors were tracked) rates.
      Linear mixed models and multiple regressions were used to examine change in
      adolescent BMI and WC z-scores and predictors of adolescent participation and
      self-monitoring, respectively. RESULTS: Adolescents and parents completed 28% and
      23%, respectively, of the online component of the intervention. Higher adolescent
      participation rate was associated with a decrease in the slope of BMI z-score but
      not with change in WC z-score. No association was found between self-monitoring
      rate and change in adolescent BMI or WC z-scores. Parent participation was not
      found to moderate the relationship between adolescent participation and weight
      outcomes. CONCLUSIONS: Developing strategies for engaging and promoting
      supportive interactions between adolescents and parents are needed in the e
      health context. Findings demonstrate that improving adolescents' adherence to e
      health lifestyle intervention can effectively alter the weight trajectory of
      overweight/obese adolescents.

PMID- 28438203
TI  - Genetic diversity of calcareous grassland plant species depends on historical
      landscape configuration.
AB  - BACKGROUND: Habitat fragmentation is considered to be a main reason for
      decreasing genetic diversity of plant species. However, the results of many
      fragmentation studies are inconsistent. This may be due to the influence of
      habitat conditions, having an indirect effect on genetic variation via
      reproduction. Consequently we took a comparative approach to analyse the impact
      of habitat fragmentation and habitat conditions on the genetic diversity of
      calcareous grassland species in this study. We selected five typical grassland
      species (Primula veris, Dianthus carthusianorum, Medicago falcata, Polygala
      comosa and Salvia pratensis) occurring in 18 fragments of calcareous grasslands
      in south eastern Germany. We sampled 1286 individuals in 87 populations and
      analysed genetic diversity using amplified fragment length polymorphisms.
      Additionally, we collected data concerning habitat fragmentation (historical and
      present landscape structure) and habitat conditions (vegetation structure, soil
      conditions) of the selected study sites. The whole data set was analysed using
      Bayesian multiple regressions. RESULTS: Our investigation indicated a habitat
      loss of nearly 80% and increasing isolation between grasslands since 1830.
      Bayesian analysis revealed a significant impact of the historical landscape
      structure, whereas habitat conditions played no important role for the present
      day genetic variation of the studied plant species. CONCLUSIONS: Our study
      indicates that the historical landscape structure may be more important for
      genetic diversity than present habitat conditions. Populations persisting in
      abandoned grassland fragments may contribute significantly to the species'
      variability even under deteriorating habitat conditions. Therefore, these
      populations should be included in approaches to preserve the genetic variation of
      calcareous grassland species.

PMID- 28438205
TI  - Expression of the Clonostachys rosea lactonohydrolase gene by Lactobacillus
      reuteri to increase its zearalenone-removing ability.
AB  - BACKGROUND: Mycotoxins are secondary metabolites produced by filamentous fungi
      that can contaminate agricultural crops in the field as well as during harvest,
      transportation, processing, or storage. Zearalenone (ZEN), a non-steroidal
      estrogenic mycotoxin, produced by Fusarium species, has been shown to be
      associated with reproductive disorders in farm animals and to a lesser extent in
      hyperoestrogenic syndromes in humans. Thus, the decontamination of ZEN in foods
      and feeds is an important issue. RESULTS: In this study, the gene encoding
      ZHD101, a ZEN-degrading enzyme produced by Clonostachys rosea IFO 7063, was
      cloned into an Escherichia coli-Lactobacillus shuttle vector, pNZ3004, and the
      resultant plasmid pNZ-zhd101 was then introduced via electroporation into
      Lactobacillus reuteri Pg4, a probiotic strain isolated from the gastrointestinal
      tract of broilers. The transformed strain L. reuteri pNZ-zhd101 acquired the
      capacity to degrade ZEN. In addition, the production of recombinant ZHD101 did
      not affect cell growth, acid and bile salt tolerance, and had only a minor effect
      on the adhesion ability of L. reuteri pNZ-zhd101. CONCLUSIONS: To the best of our
      knowledge, this is the first report of successful expression of a ZEN-degrading
      enzyme by intestinal lactobacilli.

PMID- 28438204
TI  - Evidence on anti-malarial and diagnostic markets in Cambodia to guide malaria
      elimination strategies and policies.
AB  - BACKGROUND: Understanding Cambodia's anti-malarial and diagnostic landscape in
      2015 is critical for informing and monitoring strategies and policies as Cambodia
      moves forward with national efforts to eliminate malaria. The aim of this paper
      is to present timely and key findings on the public and private sector anti
      malarial and diagnostic landscape in Cambodia. This evidence can serve as a
      baseline benchmark for guiding implementation of national strategies as well as
      other regional initiatives to address malaria elimination activities. METHODS:
      From August 17th to October 1st, 2015, a cross sectional, nationally
      representative malaria outlet survey was conducted in Cambodia. A census of all
      public and private outlets with potential to distribute malaria testing and/or
      treatment was conducted among 180 communes. An audit was completed for all anti
      malarials, malaria rapid diagnostic tests (RDT) and microscopy. RESULTS: A total
      of 26,664 outlets were screened, and 1303 outlets were eligible and interviewed.
      Among all screened outlets in the public sector, 75.9% of public health
      facilities and 67.7% of community health workers stocked both malaria diagnostic
      testing and a first-line artemisinin-based combination therapy (ACT). Among anti
      malarial-stocking private sector outlets, 64.7% had malaria blood testing
      available, and 70.9% were stocking a first-line ACT. Market share data illustrate
      that most of the anti-malarials were sold or distributed through the private
      sector (58.4%), including itinerant drug vendors (23.4%). First-line ACT
      accounted for the majority of the market share across the public and private
      sectors (90.3%). Among private sector outlets stocking any anti-malarial, the
      proportion of outlets with a first-line ACT or RDT was higher among outlets that
      had reportedly received one or more forms of 'support' (e.g. reportedly received
      training in the previous year on malaria diagnosis [RDT and/or microscopy] and/or
      the national treatment guidelines for malaria) compared to outlets that did not
      report receiving any support (ACT: 82.1 and 60.6%, respectively; RDT: 78.2 and
      64.0%, respectively). CONCLUSION: The results point to high availability and
      distribution of first-line ACT and widespread availability of malaria diagnosis,
      especially in the public sector. This suggests that there is a strong foundation
      for achieving elimination goals in Cambodia. However, key gaps in terms of
      availability of malaria commodities for case management must be addressed,
      particularly in the private sector where most people seek treatment. Continued
      engagement with the private sector will be important to ensure accelerated
      progress towards malaria elimination.

PMID- 28438206
TI  - Exogenous gene transfer of Rab38 small GTPase ameliorates aberrant lung
      surfactant homeostasis in Ruby rats.
AB  - BACKGROUND: Rab38 small GTPase regulates intracellular transport in melanocytes
      and alveolar type II epithelial cells. Ruby rats carrying Rab38 and other gene
      mutations exhibit oculocutaneous albinism, bleeding diathesis, and hence, are a
      rat model of human Hermansky-Pudlak syndrome (HPS). We previously showed that
      Long Evans Cinnamon (LEC) rats, one strain of the Ruby rats, developed aberrant
      lung surfactant homeostasis with remarkably enlarged lamellar bodies in alveolar
      type II cells. METHODS: A replication-deficient recombinant adenovirus expressing
      rat Rab38 (Ad-Rab38) was constructed. Alveolar type II cells were isolated from
      the LEC rats and tested for lung surfactant phosphatidylcholine secretion. The
      rats were also examined whether exogenous expression of Ad- Rab38 could rescue
      the altered lung surfactant homeostasis in the lungs. RESULTS: Isolated type II
      cells infected with Ad-Rab38 exhibited improved secretion patterns of
      [3H]phosphatidylcholine, i.e. increased basal hyposecretion and decreased agonist
      induced hypersecretion. Endobronchial administration of Ad-Rab38 improved the
      morphology of type II cells and lamellar bodies, reducing their sizes close to
      those of wild-type rats. The increased amounts of phosphatidylcholine and
      surfactant protein B in the lamellar body fractions were decreased in the Ad
      Rab38 infected lungs. CONCLUSIONS: These results provide strong evidence that the
      aberrant lung surfactant homeostasis in the LEC rats is caused by Rab38 deficit,
      and suggest that endobronchial delivery of the responsive transgene could be an
      effective method to ameliorate the abnormal lung phenotype in the animal model of
      HPS.

PMID- 28438207
TI  - Large scale validation of an efficient CRISPR/Cas-based multi gene editing
      protocol in Escherichia coli.
AB  - BACKGROUND: The exploitation of the CRISPR/Cas9 machinery coupled to lambda
      (lambda) recombinase-mediated homologous recombination (recombineering) is
      becoming the method of choice for genome editing in E. coli. First proposed by
      Jiang and co-workers, the strategy has been subsequently fine-tuned by several
      authors who demonstrated, by using few selected loci, that the efficiency of
      mutagenesis (number of mutant colonies over total number of colonies analyzed)
      can be extremely high (up to 100%). However, from published data it is difficult
      to appreciate the robustness of the technology, defined as the number of
      successfully mutated loci over the total number of targeted loci. This
      information is particularly relevant in high-throughput genome editing, where
      repetition of experiments to rescue missing mutants would be impractical. This
      work describes a "brute force" validation activity, which culminated in the
      definition of a robust, simple and rapid protocol for single or multiple gene
      deletions. RESULTS: We first set up our own version of the CRISPR/Cas9 protocol
      and then we evaluated the mutagenesis efficiency by changing different parameters
      including sequence of guide RNAs, length and concentration of donor DNAs, and use
      of single stranded and double stranded donor DNAs. We then validated the
      optimized conditions targeting 78 "dispensable" genes. This work led to the
      definition of a protocol, featuring the use of double stranded synthetic donor
      DNAs, which guarantees mutagenesis efficiencies consistently higher than 10% and
      a robustness of 100%. The procedure can be applied also for simultaneous gene
      deletions. CONCLUSIONS: This work defines for the first time the robustness of a
      CRISPR/Cas9-based protocol based on a large sample size. Since the technical
      solutions here proposed can be applied to other similar procedures, the data
      could be of general interest for the scientific community working on bacterial
      genome editing and, in particular, for those involved in synthetic biology
      projects requiring high throughput procedures.

PMID- 28438209
TI  - Selective episiotomy vs. implementation of a non-episiotomy protocol: a
      randomized clinical trial.
AB  - BACKGROUND: Despite all the evidence corroborating the selective use of
      episiotomy and although routine use of the procedure is contraindicated, there
      are no evidences corroborating if episiotomy is necessary in any circumstance.
      The present clinical randomized trial was performed to compare maternal and
      perinatal outcomes in women submitted to a non-episiotomy protocol versus one of
      selective episiotomy. METHODS: An open-labelled, randomized clinical trial was
      carried out in a tertiary teaching hospital in Recife, Northeastern Brazil. Women
      in labor with a full-term live foetus, dilatation of 6 to 8 cm and cephalic
      presentation (vertex position) were included. Exclusion criteria consisted of
      bleeding disorders and an indication for a caesarean section. After signing the
      consent form, 241 women were randomized to a non-episiotomy protocol (the
      experimental group) or to a selective episiotomy group (the control group). No
      episiotomies were to be performed in the experimental group except under
      exceptional circumstances. In the control group, selective episiotomies were to
      be performed in accordance with the healthcare professionals' clinical judgement.
      Maternal and perinatal outcomes were evaluated. Ratio Risk (RR) and the 95%
      confidence interval (95% CI) were calculated for our outcomes. RESULTS: The
      analysis include 115 women assigned to a non-episiotomy protocol and 122 to
      selective episiotomy. There was no difference between the two groups with respect
      to maternal or perinatal outcomes. The episiotomy rate was similar (two cases in
      each group, about 1.7%), as was the duration of the second stage of labor, the
      frequency of perineal tears, severe perineal trauma, need for perineal suturing
      and blood loss at delivery. CONCLUSIONS: A non-episiotomy protocol appears to be
      safe for mother and child, and highlights the need to investigate whether there
      is, in fact, any indication for this procedure. TRIAL REGISTRATION: This trial
      was registered at ClinicalTrials.gov under reference number ( NCT02178111 ).

PMID- 28438208
TI  - Amelioration of amyloid-beta-induced deficits by DcR3 in an Alzheimer's disease
      model.
AB  - BACKGROUND: Microglia mediate amyloid-beta peptide (Abeta)-induced
      neuroinflammation, which is one of the key events in the pathogenesis of
      Alzheimer's disease (AD). Decoy receptor 3 (DcR3)/TNFRSF6B is a pleiotropic
      immunomodulator that promotes macrophage differentiation toward the M2 anti
      inflammatory phenotype. Based on its role as an immunosupressor, we examined
      whether DcR3 could alleviate neuroinflammation and AD-like deficits in the
      central nervous system. METHOD: We crossed human APP transgenic mice (line J20)
      with human DcR3 transgenic mice to generate wild-type, APP, DcR3, and APP/DcR3
      mice for pathological analysis. The Morris water maze, fear conditioning test,
      open-field, and elevated-plus maze were used to access their cognitive behavioral
      changes. Furthermore, the pathological and immune profiles were examined by
      immunostaining, ELISA, Q-PCR, and IP. In vitro assays were designed to examine
      DcR3-mediated innate cytokine profile alteration and the potential protective
      mechanism. RESULTS: We reported that DcR3 ameliorates hippocampus-dependent
      memory deficits and reduces amyloid plaque deposition in APP transgenic mouse.
      The protective mechanism of DcR3 mediates through interacting with heparan
      sulfate proteoglycans and activating IL-4+YM1+ M2a-like microglia that reduces
      Abeta-induced proinflammatory cytokines and promotes phagocytosis ability of
      microglia. CONCLUSION: The neuroprotective effect of DcR3 is mediated via
      modulating microglia activation into anti-inflammatory M2a phenotype, and
      upregulating DcR3 expression in the brain may be a potential therapeutic approach
      for AD.

PMID- 28438210
TI  - Specific and quantitative detection of Human polyomaviruses BKPyV and JCPyV in
      the healthy Pakistani population.
AB  - BACKGROUND: The BK Polyomavirus (BKPyV) and JC polyomavirus (JCPyV) infections
      are widespread in human population and have been associated with severe kidney
      and brain disorders, respectively. The viruses remain latent primarily in reno
      urinary tract, reactivating only in case of a compromised immune system. The
      seroepidemiology and molecular prevalence of BKPyV and JCPyV have been widely
      studied both in healthy and immunocompromised patients worldwide. However, data
      regarding the prevalence of these viruses in the immunocompetent or apparently
      healthy Pakistani population is lacking. Herein, we present the first ever report
      on quantitative prevalence of BKPyV and JCPyV in the peripheral blood of a
      randomly selected cohort of healthy Pakistani population. METHODS: A total of 266
      whole blood samples were examined. The subjects were divided into three age
      groups: <= 25 years (young), 26-50 years (middle) and >= 51 years (elder).
      Absolute real time PCR assay was designed to quantify the BKPyV and JCPyV viral
      copy numbers in the range of 106 to 100 copies/mL. RESULTS: Overall, BKPyV was
      detected in 27.1% (72/266) individuals while JCPyV in 11.6% (31/266) indicating
      significant difference (p < 0.005) in the distribution of these two viruses. The
      prevalence of BKPyV significantly decreased from 51% (49/96) in young age group
      to 8.2% (7/85) in eldest age group. Whereas, JCPyV positivity rate slightly
      increased from 8.3% (8/96) in young age group to 11.8% (10/85) in elder age
      group. The median viral load was calculated as 6.2 log and 3.38 log copies/mL of
      blood for BKPyV and JCPyV, respectively. Notably, no significant difference in
      viral load of either of the subtypes was found between different age groups.
      CONCLUSION: The current study provides an important baseline data on the
      prevalence and viral load of circulating BKPyV and JCPyV in Pakistani population.
      The prevalence and viral load of BKPyV was comparatively higher than JCPyV. The
      prevalence of BKPyV significantly decreased with increase in age while JCPyV
      positivity rate slightly increased with increasing age. Viral load of both BKPyV
      and JCPyV was not correlated with the individual ages.

PMID- 28438211
TI  - Social and behavioral interventions for improving quality of life of HIV infected
      people receiving antiretroviral therapy: a systematic review and meta-analysis.
AB  - BACKGROUND: Improvement in quality of life is crucial for HIV infected people.
      Social and behavioral interventions have been implemented in different contexts
      to improve the quality of life among HIV infected people. This review appraises
      the evidence for available interventions that focused on quality of life of HIV
      infected people receiving antiretroviral therapy (ART). METHODS: We searched
      electronic databases for randomized controlled trials of interventions to improve
      the quality of life of HIV infected people receiving ART. We searched PUBMED and
      the Cochrane Centre Register of Controlled Trials (CENTRAL) with the terms
      "social", "behavioral", "educational", "quality of life", "HIV", and "RCT".
      Searches were conducted for articles published from 1980 to December 16, 2015.
      Standardized data abstraction methods and searching steps were applied. RESULTS:
      Twenty-eight studies reported the impact of social or behavioral interventions in
      quality of life among HIV infected people, of which 15 were conducted in United
      States of America. A total of 4136 participants were enrolled. Of the 28 studies,
      four studies included females, two studies included males and remaining studies
      excluded both males and females. The overall reported methodological quality of
      the studies was subject to a high risk of bias and the study criteria were
      unclear in most studies. Twenty-one studies reported a significant intervention
      effect on at least one quality of life domain. Meta-analyses showed significant
      improvement in general health, mental health, physical function and environment
      domains of quality of life among intervention groups. However, the expected
      impact of the intervention was low to moderate because the rigorousness of the
      studies was low, information was limited, the sample sizes were small and other
      the quality of the study designs were poor. CONCLUSIONS: Although the available
      evidence suggests that existing social and behavioral interventions can improve
      some quality of life domains, the quality of evidence was insufficient to support
      the notion that these interventions can improve the overall quality of life of
      HIV infected people receiving ART. Well-designed and rigorous randomized
      controlled trials with high methodological quality are required.

PMID- 28438212
TI  - Primary follicular dendritic cell sarcoma of the urinary bladder: the first case
      report and potential diagnostic pitfalls.
AB  - BACKGROUND: Extranodal follicular dendritic cell sarcoma (FDCS) is a very rare
      malignancy with a variable clinical course. It is often not considered and has
      the potential to result in a misdiagnosis of other common sarcomas or sarcomatoid
      carcinomas. This is particularly true with the preoperative biopsy specimen, in
      which the tissue sample is often small. CASE PRESENTATION: A case of FDCS in a 63
      year-old woman, arising in the urinary bladder, a previously unreported site, is
      described. The patient presented with the typical clinical symptoms of a bladder
      cancer, and the morphology of the tumor was similar to a lymphoepithelioma-like
      carcinoma, ultimately resulting in it being misdiagnosed. The patient received
      radical cystectomy, without further radiotherapy or chemotherapy. Two years after
      operation, a metastatic tumor to the lung was found. The mass of the right main
      bronchus lumen was frozen and resected through bronchoscopy, and radiotherapy was
      performed. The patient has lived with the tumor since then. CONCLUSIONS: This
      paper presents the first FDCS occurring in the urinary bladder with metastasis to
      the lung and emphasizes potential diagnostic pitfalls.

PMID- 28438213
TI  - Cervid herpesvirus 2 and not Moraxella bovoculi caused keratoconjunctivitis in
      experimentally inoculated semi-domesticated Eurasian tundra reindeer.
AB  - BACKGROUND: Infectious keratoconjunctivitis (IKC) is a transmissible disease in
      semi-domesticated Eurasian reindeer (Rangifer tarandus tarandus). It is regarded
      as multifactorial and a single causative pathogen has not yet been identified.
      From clinical outbreaks we have previously identified Cervid herpesvirus 2
      (CvHV2) and Moraxella bovoculi as candidates for experimental investigations.
      Eighteen reindeer were inoculated in the right eye with CvHV2 (n = 5), M.
      bovoculi (n = 5), CvHV2 and M. bovoculi (n = 5) or sterile saline water (n = 3;
      controls). RESULTS: All animals inoculated with CvHv2, alone or in combination
      with M. bovoculi, showed raised body temperature, increased lacrimation,
      conjunctivitis, excretion of pus and periorbital oedema; clinical signs that
      increased in severity from day 2 post inoculation (p.i.) and throughout the
      experiment, until euthanasia 5-7 days p.i. Examination after euthanasia revealed
      corneal oedema, and three animals displayed a corneal ulcer. CvHV2 could be
      identified in swab samples from both the inoculated eye and the control eye from
      most animals and time points, indicating a viral spread from the inoculation
      site. CONCLUSIONS: This study showed that CvHV2 alone and in combination with M.
      bovoculi was able to cause the characteristic clinical signs of IKC in reindeer,
      whereas inoculation of M. bovoculi alone, originally isolated from a reindeer
      with IKC, did not produce clinical signs. Previous studies have suggested that
      herding procedures, animal stress and subsequent reactivation of latent CvHV2
      infection in older animals is a plausible mechanism for IKC outbreaks among
      reindeer calves and young animals in reindeer herds. However, further studies are
      needed to fully understand the infection biology and epidemiology associated with
      IKC in reindeer.

PMID- 28438214
TI  - Predictors of job satisfaction among nurses working in Ethiopian public
      hospitals, 2014: institution-based cross-sectional study.
AB  - BACKGROUND: Nurses play a pivotal role in determining the efficiency,
      effectiveness, and sustainability of health care systems. Nurses' job
      satisfaction plays an important role in the delivery of quality health care.
      There is paucity of studies addressing job satisfaction among nurses in the
      public hospital setting in Ethiopia. Thus, this study aimed to assess job
      satisfaction and factors influencing it among nurses in Jimma zone public
      hospitals, southwestern Ethiopia. METHODS: An institution-based census was
      conducted among 316 nurses working in Jimma zone public hospitals from March to
      April, 2014. A structured self-administered questionnaire based on a modified
      version of the McCloskey/Mueller Satisfaction Scale was used. Data were entered
      using Epi Info version 3.5.3 statistical software and analyzed using SPSS version
      20 statistical package. Mean satisfaction scores were compared by independent
      variables using an independent sample t test and ANOVA. Bivariate and
      multivariable linear regressions were done. RESULTS: A total of 316 nurses were
      included, yielding a response rate of 92.67%. The overall mean job satisfaction
      was (67.43 +/- 13.85). One third (33.5%) of the study participants had a low
      level of job satisfaction. Mutual understandings at work and professional
      commitment showed significant and positive relationship with overall job
      satisfaction, while working at an inpatient unit and work load were negatively
      associated. CONCLUSIONS: One third of nurses had a low level of job satisfaction.
      Professional commitment, workload, working unit, and mutual understanding at work
      predicted the outcome variable.

PMID- 28438215
TI  - Predicting liver SBRT eligibility and plan quality for VMAT and 4pi plans.
AB  - BACKGROUND: It is useful to predict planned dosimetry and determine the
      eligibility of a liver cancer patient for SBRT treatment using knowledge based
      planning (KBP). We compare the predictive accuracy using the overlap volume
      histogram (OVH) and statistical voxel dose learning (SVDL) KBP prediction models
      for coplanar VMAT to non-coplanar 4pi radiotherapy plans. METHODS: In this study,
      21 liver SBRT cases were selected, which were initially treated using coplanar
      VMAT plans. They were then re-planned using 4pi IMRT plans with 20 inversely
      optimized non-coplanar beams. OVH was calculated by expanding the planning target
      volume (PTV) and then plotting the percent overlap volume v with the liver vs. r
      v , the expansion distance. SVDL calculated the distance to the PTV for all liver
      voxels and bins the voxels of the same distance. Their dose information is
      approximated by either taking the median or using a skew-normal or non-parametric
      fit, which was then applied to voxels of unknown dose for each patient in a leave
      one-out test. The liver volume receiving less than 15 Gy (V<15Gy), DVHs, and 3D
      dose distributions were predicted and compared between the prediction models and
      planning methods. RESULTS: On average, V<15Gy was predicted within 5%. SVDL was
      more accurate than OVH and able to predict DVH and 3D dose distributions. Median
      SVDL yielded predictive errors similar or lower than the fitting methods and is
      more computationally efficient. Prediction of the 4pi dose was more accurate
      compared to VMAT for all prediction methods, with significant (p < 0.05) results
      except for OVH predicting liver V<15Gy (p = 0.063). CONCLUSIONS: In addition to
      evaluating plan quality, KBP is useful to automatically determine the patient
      eligibility for liver SBRT and quantify the dosimetric gains from non-coplanar
      4pi plans. The two here analyzed dose prediction methods performed more
      accurately for the 4pi plans than VMAT.

PMID- 28438216
TI  - Improved pressure contour analysis for estimating cardiac stroke volume using
      pulse wave velocity measurement.
AB  - BACKGROUND: Pressure contour analysis is commonly used to estimate cardiac
      performance for patients suffering from cardiovascular dysfunction in the
      intensive care unit. However, the existing techniques for continuous estimation
      of stroke volume (SV) from pressure measurement can be unreliable during
      hemodynamic instability, which is inevitable for patients requiring significant
      treatment. For this reason, pressure contour methods must be improved to capture
      changes in vascular properties and thus provide accurate conversion from pressure
      to flow. METHODS: This paper presents a novel pressure contour method utilizing
      pulse wave velocity (PWV) measurement to capture vascular properties. A three
      element Windkessel model combined with the reservoir-wave concept are used to
      decompose the pressure contour into components related to storage and flow. The
      model parameters are identified beat-to-beat from the water-hammer equation using
      measured PWV, wave component of the pressure, and an estimate of subject-specific
      aortic dimension. SV is then calculated by converting pressure to flow using
      identified model parameters. The accuracy of this novel method is investigated
      using data from porcine experiments (N = 4 Pietrain pigs, 20-24.5 kg), where
      hemodynamic properties were significantly altered using dobutamine, fluid
      administration, and mechanical ventilation. In the experiment, left ventricular
      volume was measured using admittance catheter, and aortic pressure waveforms were
      measured at two locations, the aortic arch and abdominal aorta. RESULTS: Bland
      Altman analysis comparing gold-standard SV measured by the admittance catheter
      and estimated SV from the novel method showed average limits of agreement of +/
      26% across significant hemodynamic alterations. This result shows the method is
      capable of estimating clinically acceptable absolute SV values according to
      Critchely and Critchely. CONCLUSION: The novel pressure contour method presented
      can accurately estimate and track SV even when hemodynamic properties are
      significantly altered. Integrating PWV measurements into pressure contour
      analysis improves identification of beat-to-beat changes in Windkessel model
      parameters, and thus, provides accurate estimate of blood flow from measured
      pressure contour. The method has great potential for overcoming weaknesses
      associated with current pressure contour methods for estimating SV.

PMID- 28438217
TI  - A powerful microbiome-based association test and a microbial taxa discovery
      framework for comprehensive association mapping.
AB  - BACKGROUND: The role of the microbiota in human health and disease has been
      increasingly studied, gathering momentum through the use of high-throughput
      technologies. Further identification of the roles of specific microbes is
      necessary to better understand the mechanisms involved in diseases related to
      microbiome perturbations. METHODS: Here, we introduce a new microbiome-based
      group association testing method, optimal microbiome-based association test
      (OMiAT). OMiAT is a data-driven testing method which takes an optimal test
      throughout different tests from the sum of powered score tests (SPU) and
      microbiome regression-based kernel association test (MiRKAT). We illustrate that
      OMiAT efficiently discovers significant association signals arising from varying
      microbial abundances and different relative contributions from microbial
      abundance and phylogenetic information. We also propose a way to apply it to fine
      mapping of diverse upper-level taxa at different taxonomic ranks (e.g., phylum,
      class, order, family, and genus), as well as the entire microbial community,
      within a newly introduced microbial taxa discovery framework, microbiome
      comprehensive association mapping (MiCAM). RESULTS: Our extensive simulations
      demonstrate that OMiAT is highly robust and powerful compared with other existing
      methods, while correctly controlling type I error rates. Our real data analyses
      also confirm that MiCAM is especially efficient for the assessment of upper-level
      taxa by integrating OMiAT as a group analytic method. CONCLUSIONS: OMiAT is
      attractive in practice due to the high complexity of microbiome data and the
      unknown true nature of the state. MiCAM also provides a hierarchical association
      map for numerous microbial taxa and can also be used as a guideline for further
      investigation on the roles of discovered taxa in human health and disease.

PMID- 28438218
TI  - Malaria elimination in Lao PDR: the challenges associated with population
      mobility.
AB  - Although the Lao People's Democratic Republic (Lao PDR) is comparatively small
      landlocked country with patterns of both in- and out-migration, its human
      migration situation has been poorly studied. This is despite all of the country's
      18 provinces sharing both official and unofficial border checkpoints with
      neighboring countries. Economic reforms in the last decade have seen a gradual
      increase in the promotion of foreign investment, and main towns and
      transportation networks have been expanding thus offering new opportunities for
      livelihoods and economic activities.In the last decade, there has also been a
      significant reduction of reported malaria cases in Lao PDR and while this is an
      important prerequisite for eliminating malaria in the country, malaria outbreaks
      reported in the last four years suggest that population mobility, particularly in
      the south, is an important factor challenging current control efforts.Bolder
      investment in social sector spending should be geared towards improving health
      service provision and utilization, ensuring equitable access to primary health
      care (including malaria) through efforts to achieve universal health coverage
      targets. This should be extended to populations that are mobile and migrants. The
      local government plays a critical role in supporting policy and enforcement
      issues related to private sector project development in the provinces. Cross
      border initiatives with neighboring countries, especially in terms of data
      sharing, surveillance, and response, is essential. Mechanisms to engage the
      private sector, especially the informal private sector, needs to be explored
      within the context of existing regulations and laws. Existing and new
      interventions for outdoor transmission of malaria, especially in forest settings,
      for high-risk groups including short- and long-term forest workers and their
      families, mobile and migrant populations, as well as the military must be
      combined into integrated packages with innovative delivery mechanisms through
      social marketing approaches. This should happen at multiple points in the
      mobility pathway and involve the private sector rather than being fully reliant
      on the national malaria vertical programThis article based on the review of
      existing literature from abstracts and full texts, includes published, peer
      reviewed English language literature sourced through PubMed and grey literature
      sources through Google and Google Scholar. The review included also case reports,
      sector reports, conference proceedings, research reports, epidemiology studies,
      qualitative studies, and census reports in both Lao and English languages. The
      authors used the search terms: malaria and mobile populations, malaria control
      program and elimination, health system performance, malaria outbreak, Lao PDR;
      and included articles published until June 2015.

PMID- 28438219
TI  - Adverse drug reactions and kinetics of cisplatin excretion in urine of patients
      undergoing cisplatin chemotherapy and radiotherapy for head and neck cancer: a
      prospective study.
AB  - BACKGROUND: Cisplatin is a high-potency anticancer agent; however, it causes
      significant adverse drug reactions (ADRs). Potential pharmacokinetic markers must
      be studied to predict or prevent cisplatin-induced ADRs and achieve better
      prognosis. This study was designed to investigate the relationship between ADRs
      and kinetics of cisplatin excretion in the urine of patients undergoing high-dose
      cisplatin chemotherapy and radiotherapy for head and neck cancer. METHODS:
      Outpatients with head and neck cancer received a first cycle of high-dose
      cisplatin chemotherapy (80-100 mg/m2) concurrent to radiotherapy. ADRs
      (haematological, renal, and gastrointestinal reactions) were classified based on
      severity by National Cancer Institute Common Terminology Criteria for Adverse
      Events (CTCAE, version 4, grade 0-4). The kinetics of cisplatin excretion in
      urine was evaluated by high-performance liquid chromatography over three time
      periods: 0-12, 12-24, and 24-48 h after the administration of cisplatin. Spearman
      Correlation test and regression analysis were performed to assess the
      relationship between ADRs and cisplatin excretion in the urine. RESULTS: In
      total, 59 patients with a mean age of 55.6 +/- 9.4 years were analysed; most
      patients were male (86.4%), white (79.7%), and with pharyngeal tumours in
      advanced stages (66.1%). The most frequently observed ADRs were anaemia (81.4%),
      lymphopenia (78%), and nausea (64.4%); mostly grades 1 and 2 of toxicity. The
      mean cisplatin excretion was 70.3 +/- 64.4, 7.3 +/- 6.3, and 5 +/- 4 MUg/mg
      creatinine at 0-12, 12-24, and 24-48 h, respectively. Statistical analysis showed
      that the amount of cisplatin excreted did not influence the severity of ADRs.
      CONCLUSIONS: The most frequent ADRs were anaemia, lymphopenia, and nausea. Grades
      1 and 2 were the severities for most ADRs. The period over which the highest
      cisplatin excretion observed was 0-12 h after chemotherapy, and cisplatin
      excretion could not predict toxicity.

PMID- 28438220
TI  - Anaplasma spp. in dogs and owners in north-western Morocco.
AB  - BACKGROUND: Anaplasma phagocytophilum is an emerging tick-borne zoonotic pathogen
      of increased interest worldwide which has been detected in northern Africa.
      Anaplasma platys is also present in this region and could possibly have a
      zoonotic potential. However, only one recent article reports on the human
      esposure to A. phagocytophilum in Morocco and no data are available on canine
      exposure to both bacteria. Therefore, we conducted a cross-sectional
      epidemiological study aiming to assess both canine and human exposure to
      Anaplasma spp. in Morocco. A total of 425 dogs (95 urban, 160 rural and 175
      working dogs) and 11 dog owners were sampled from four cities of Morocco. Canine
      blood samples were screened for Anaplasma spp. antibodies by an enzyme-linked
      immunosorbent assay (ELISA) and for A. phagocytophilum and A. platys DNA by a
      real-time polymerase chain reaction (RT-PCR) targeting the msp2 gene. Human sera
      were tested for specific A. phagocytophilum immunoglobulin G (IgG) using a
      commercial immunofluorescence assay (IFA) kit. RESULTS: Anaplasma spp. antibodies
      and A. platys DNA were detected in 21.9 and 7.5% of the dogs, respectively.
      Anaplasma phagocytophilum DNA was not amplified. Anaplasma platys DNA was
      significantly more frequently amplified for working dogs. No statistically
      significant differences in the prevalence of Anaplasma spp. antibodies or A.
      platys DNA detection were observed between sexes, age classes or in relation to
      exposure to ticks. A total of 348 Rhipicephalus sanguineus (sensu lato) ticks
      were removed from 35 urban and working dogs. The majority of dog owners (7/10)
      were seroreactive to A. phagoyctophilum IgG (one sample was excluded because of
      hemolysis). CONCLUSIONS: This study demonstrates the occurrence of Anaplasma spp.
      exposure and A. platys infection in dogs, and A. phagocytophilum exposure in
      humans in Morocco.

PMID- 28438221
TI  - Isolated splenic tuberculosis with subsequent paradoxical deterioration: a case
      report.
AB  - BACKGROUND: Isolated tuberculosis of the spleen has been described occasionally
      in literature, mostly in immunosuppressed individuals with various risk factors.
      Sequestration in the spleen makes such Mycobacterium tuberculosis infection
      difficult to diagnose. This report describes an extremely rare case of isolated
      splenic tuberculosis in an immunocompetent individual. CASE PRESENTATION: A 26
      year old Kenyan male presented with pyrexia of unknown origin, with negative
      screening tests for bacterial, fungal and parasitic infections. Ziehl-Neelsen
      staining and GeneXpert tests were negative for M. tuberculosis. Diagnosis of
      isolated splenic tuberculosis was made on core biopsy of the spleen. The patient
      initially worsened upon treatment with antituberculous medication attributable to
      the 'Paradoxical Reaction' phenomenon, before making full recovery. CONCLUSIONS:
      This case highlights the need to continuously be on the lookout for tuberculosis
      especially in unusual presentations, including subsequent paradoxical reaction
      which may be encountered.

PMID- 28438222
TI  - Hypothermia in trauma victims at first arrival of ambulance personnel: an
      observational study with assessment of risk factors.
AB  - BACKGROUND: Hypothermia is common in trauma victims and is associated with
      increased mortality, however its causes are little known. The objective of this
      study was to identify the risk factors associated with hypothermia in prehospital
      management of trauma victims. METHODS: This was an ancillary analysis of data
      recorded in the HypoTraum study, a prospective multicenter study conducted by the
      emergency medical services (EMS) of 8 hospitals in France. Inclusion criteria
      were: trauma victim, age over 18 years, and victim receiving prehospital care
      from an EMS team and transported to hospital by the EMS team in a medically
      equipped mobile intensive care unit. The following data were recorded: victim
      demographics, circumstances of the trauma, environmental factors, patient
      presentation, clinical data and time from accident to EMS arrival. Independent
      risk factors for hypothermia were analyzed in a multivariate logistic regression
      model. RESULTS: A total of 461 trauma patients were included in the study. Road
      traffic accidents (N = 261; 57%) and falls (N = 65; 14%) were the main causes of
      trauma. Hypothermia (<35  degrees C) was present in 136/461 cases (29%).
      Independent factors significantly associated with the presence of hypothermia
      were: a low GCS (Odds Ratio (OR) = 0,87 ([0,81-0,92]; p < 0.0001), a low air
      temperature (OR = 0,93 [0,91-0,96]; p < 0.0001) and a wet patient (OR = 2,08
      [1,08-4,00]; p = 0.03). CONCLUSION: The incidence of hypothermia was high on EMS
      arrival at the scene. Body temperature measurement and immediate thermal
      protection should be routine, and special attention should be given to patients
      who are wet. LEVEL OF EVIDENCE: Prospective, multicenter, open, observational
      study; Level IV.

PMID- 28438223
TI  - Extrastriatal changes in patients with late-onset glutaric aciduria type I
      highlight the risk of long-term neurotoxicity.
AB  - BACKGROUND: Without neonatal initiation of treatment, 80-90% of patients with
      glutaric aciduria type 1 (GA1) develop striatal injury during the first six years
      of life resulting in a complex, predominantly dystonic movement disorder. Onset
      of motor symptoms may be acute following encephalopathic crisis or insidious
      without apparent crisis. Additionally, so-called late-onset GA1 has been
      described in single patients diagnosed after the age of 6 years. With the aim of
      better characterizing and understanding late-onset GA1 we analyzed clinical
      findings, biochemical phenotype, and MRI changes of eight late-onset patients and
      compared these to eight control patients over the age of 6 years with early
      diagnosis and start of treatment. RESULTS: No late-onset or control patient had
      either dystonia or striatal lesions on MRI. All late-onset (8/8) patients were
      high excretors, but only four of eight control patients. Two of eight late-onset
      patients were diagnosed after the age of 60 years, presenting with dementia,
      tremor, and epilepsy, while six were diagnosed before the age of 30 years: Three
      were asymptomatic mothers identified by following a positive screening result in
      their newborns and three had non-specific general symptoms, one with additional
      mild neurological deficits. Frontotemporal hypoplasia and white matter changes
      were present in all eight and subependymal lesions in six late-onset patients. At
      comparable age a greater proportion of late-onset patients had (non-specific)
      clinical symptoms and possibly subependymal nodules compared to control patients,
      in particular in comparison to the four clinically and MR-wise asymptomatic low
      excreting control patients. CONCLUSIONS: While clinical findings are non
      specific, frontotemporal hypoplasia and subependymal nodules are characteristic
      MRI findings of late-onset GA1 and should trigger diagnostic investigation for
      this rare disease. Apart from their apparent non-susceptibility for striatal
      injury despite lack of treatment, patients with late-onset GA1 are not
      categorically different from early treated control patients. Differences between
      late-onset patients and early treated control patients most likely reflect
      greater cumulative neurotoxicity in individuals remaining undiagnosed and
      untreated for years, even decades as well as the higher long-term risk of high
      excretors for intracerebral accumulation of neurotoxic metabolites compared to
      low excretors.

PMID- 28438224
TI  - Early strong intrathecal inflammation in cerebellar type multiple system atrophy
      by cerebrospinal fluid cytokine/chemokine profiles: a case control study.
AB  - BACKGROUND: The pathology of multiple system atrophy cerebellar-type (MSA-C)
      includes glial inflammation; however, cerebrospinal fluid (CSF) inflammatory
      cytokine profiles have not been investigated. In this study, we determined CSF
      cytokine/chemokine/growth factor profiles in MSA-C and compared them with those
      in hereditary spinocerebellar ataxia (SCA). METHODS: We collected clinical data
      and CSF from 20 MSA-C patients, 12 hereditary SCA patients, and 15 patients with
      other non-inflammatory neurological diseases (OND), and measured 27
      cytokines/chemokines/growth factors using a multiplexed fluorescent bead-based
      immunoassay. The size of each part of the hindbrain and hot cross bun sign (HCBS)
      in the pons was studied by magnetic resonance imaging. RESULTS: Granulocyte
      macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-7, IL-12,
      and IL-13 levels were significantly higher in MSA-C and SCA compared with OND. In
      MSA-C, IL-5, IL-6, IL-9, IL-12, IL-13, platelet-derived growth factor-bb,
      macrophage inflammatory protein (MIP)-1alpha, and GM-CSF levels positively
      correlated with anteroposterior diameters of the pontine base, vermis, or medulla
      oblongata. By contrast, in SCA patients, IL-12 and MIP-1alpha showed significant
      negative correlations with anteroposterior diameters of the pontine base, and
      unlike MSA-C, there was no cytokine with a positive correlation in SCA. IL-6 was
      significantly higher in MSA-C patients with the lowest grade of HCBS compared
      with those with the highest grade. Macrophage chemoattractant protein-1 (MCP-1)
      had a significant negative correlation with disease duration only in MSA-C
      patients. Tumor necrosis factor-alpha, IL-2, IL-15, IL-4, IL-5, IL-10, and IL-8
      were all significantly lower in MSA-C and SCA compared with OND, while IL-1ra, an
      anti-inflammatory cytokine, was elevated only in MSA-C. IL-1beta and IL-8 had
      positive correlations with Unified Multiple System Atrophy Rating Scale part 1
      and 2, respectively, in MSA-C. CONCLUSIONS: Although CSF
      cytokine/chemokine/growth factor profiles were similar between MSA-C and SCA, pro
      inflammatory cytokines, such as IL-6, GM-CSF, and MCP-1, correlated with the
      disease stage in a way higher at the beginning only in MSA-C, reflecting early
      stronger intrathecal inflammation.

PMID- 28438225
TI  - Meta-analysis of the parasitic phase traits of Haemonchus contortus infection in
      sheep.
AB  - BACKGROUND: The parasitic nematode Haemonchus contortus shows highly variable
      life history traits. This highlights the need to have an average estimate and a
      quantification of the variation around it to calibrate epidemiological models.
      METHODS: This paper aimed to quantify the main life history traits of H.
      contortus and to identify explanatory factors affecting these traits using a
      powerful method based on a systematic review and meta-analysis of current
      literature. The life history traits considered are: (i) the establishment rate of
      ingested larvae; (ii) the adult mortality rate; (iii) the fertility (i.e. the
      number of eggs laid/female/day); and (iv) fecundity of female worms (i.e. the
      number of eggs per gram of faeces). RESULTS: A total of 37 papers that report
      single experimental infection with H. contortus in sheep and published from 1960
      to 2015, were reviewed and collated in this meta-analysis. This encompassed 115
      experiments on 982 animals. Each trait was analysed using a linear model weighted
      by its inverse variance. The average (+/- SE) larval establishment rate was 0.24
      +/- 0.02, which decreased as a function of the infection dose and host age. An
      average adult mortality rate of 0.021 +/- 0.002) was estimated from the
      literature. This trait varied as a function of animal age, breed and protective
      response due to prior exposure to the parasite. Average female fertility was
      1295.9 +/- 280.4 eggs/female/day and decreased in resistant breeds and previously
      infected hosts. Average faecal egg count at necropsy was 908.5 +/- 487.1 eggs per
      gram of faeces and varied as a function of infection duration and host
      resistance. The average sex ratio of H. contortus was 0.51 +/- 0.006. CONCLUSION:
      This work is the first systematic review to summarise the available information
      on the parasitic phase of H. contortus in sheep. The results of the meta-analysis
      provide robust estimates of life history traits for parametrization of
      epidemiological models, their expected variation according to experimental
      factors, and provides correlations between these.

PMID- 28438226
TI  - N of 1 trials and the optimal individualisation of drug treatments: a systematic
      review protocol.
AB  - BACKGROUND: Guidelines and evidence-based drug treatment recommendations are
      usually based on the results of clinical trials, which have limited
      generalisability in routine clinical settings due to their restrictive
      eligibility criteria. These trials are also conducted in ideal and rigorously
      controlled settings. N of 1 trials, which are single patient multiple crossover
      studies, offer a means of increasing the evidence base and individualising care
      for individuals in clinical practice. This systematic review of the N of 1 drug
      treatment trial aims to investigate its usefulness for achieving optimal
      individualised patient care. METHODS: The following databases will be searched
      for relevant articles: MEDLINE, EMBASE, PsycINFO (all via Ovid), AMED, CINAHAL
      (via EBSCO), The Cochrane Library (including CENTRAL, NHS EED, and DARE), and Web
      of Science (Thomson Reuters). Supplementary searches will include ongoing trial
      databases and organisational websites. All N of 1 trials in which patients have
      been treated with a drug will be considered. Outcomes will include information on
      the clinical usefulness of N of 1 trials-i.e. achievement of optimal
      individualised care, health-care utilisation of patients, frequently used
      practices, experiences of clinical care or participation in N of 1 trials,
      adherence to treatment plan, and unwanted effects of the treatment. Screening of
      included papers will be undertaken independently by two reviewers, while data
      extraction and the quality of reporting will be conducted by one reviewer and
      checked by another. Both quantitative and qualitative summaries will be reported
      using appropriate methods. DISCUSSION: This review will provide new insights into
      the clinical utility of N of 1 drug trials in helping participants find the most
      acceptable treatment as defined by patients and clinicians based on the selected
      outcome measures and the perspectives of participants involved in such trials.
      Findings from this review will inform the development of a stakeholder workshop
      and guidance to help physicians find the optimum therapy for their patients and
      will help guide future research on N of 1 trials. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42016032452.

PMID- 28438228
TI  - Past editors' favourite papers published during their time in office.

PMID- 28438227
TI  - Characterization of Carbon Monoxide Exposure During Hurricane Sandy and
      Subsequent Nor'easter.
AB  - OBJECTIVE: Carbon monoxide (CO) is an odorless, colorless gas produced by fossil
      fuel combustion. On October 29, 2012, Hurricane Sandy moved ashore near Atlantic
      City, New Jersey, causing widespread morbidity and mortality, $30 to $50 billion
      in economic damage, and 8.5 million households to be without power. The
      combination of power outages and unusually low temperatures led people to use
      alternate power sources, placing many at risk for CO exposure. METHODS: We
      examined Hurricane Sandy-related CO exposures from multiple perspectives to help
      identify risk factors and develop strategies to prevent future exposures. This
      report combined data from 3 separate sources (health departments, poison centers
      via the National Poison Data System, and state and local public information
      officers). RESULTS: Results indicated that the number of CO exposures in the wake
      of Hurricane Sandy was significantly greater than in previous years. The persons
      affected were mostly females and those in younger age categories and, despite
      messaging, most CO exposures occurred from improper generator use. CONCLUSIONS:
      Our findings emphasize the continued importance of CO-related communication and
      ongoing surveillance of CO exposures to support public health response and
      prevention during and after disasters. Additionally, regional poison centers can
      be a critical resource for potential on-site management, public health promotion,
      and disaster-related CO exposure surveillance. (Disaster Med Public Health
      Preparedness. 2017;11:562-567).

PMID- 28438229
TI  - Energy drinks available in Ireland: a description of caffeine and sugar content.
AB  - OBJECTIVE: To describe the caffeine and sugar content of all energy drinks
      available on the island of Ireland. DESIGN: Two retail outlets were selected from
      each of: multinational, convenience and discount stores in Northern Ireland and
      the Republic of Ireland, and all available single-serve energy drinks were
      purchased. The cross-sectional survey was conducted in February 2015 and brand
      name, price, volume, caffeine and sugar content were recorded for each product.
      Descriptive analysis was performed. RESULTS: Seventy-eight products were
      identified on the island of Ireland (regular, n 59; diet/sugar-free/light, n 19).
      Caffeine and sugar content was in the range of 14-35 mg and 2.9-15.6 g per 100
      ml, respectively. Mean caffeine content of 102.2 mg per serving represents 25.6 %
      of the maximum intake advised for adults by the European Food Safety Authority.
      Per serving, mean sugar content of regular energy drinks was 37 g. This exceeds
      WHO recommendations for maximum daily sugar intake of <5 % of total energy intake
      (25 g for adults consuming 8368 kJ (2000 kcal) diet). If displaying front-of-pack
      labelling, fifty-seven of the fifty-nine regular energy drinks would receive a
      Food Standards Agency 'red' colour-coded label for sugar. CONCLUSIONS: Energy
      drinks are freely available on the island of Ireland and all products surveyed
      can be defined as highly caffeinated products. This has potential health issues
      particularly for children and adolescents where safe limits of caffeine have not
      been determined. Energy drinks surveyed also contained high levels of sugar and
      could potentially contribute to weight gain and adverse dental health effects.

PMID- 28438230
TI  - Multiple Norovirus Outbreaks Due to Shredded, Dried, Laver Seaweed in Japan.

PMID- 28438231
TI  - HEALTH TECHNOLOGY ASSESSMENT IN EVALUATION OF PHARMACEUTICALS IN THE CZECH
      REPUBLIC.
AB  - OBJECTIVES: In the Czech Republic, the health technology assessment (HTA)
      approaches have been implemented in evaluation of medicinal products since 2008.
      The aim of this study was to provide an overview of the implementation of HTA and
      different levels thereof in the evaluation process conducted by the State
      Institute for Drug Control (SUKL) and to describe the impact of HTA on the
      entrance of new medicinal entities into out-patient healthcare system including
      highly innovative and orphan drugs. METHODS: Materials supporting this overview
      were collected using the records in the database of administrative proceedings of
      SUKL, in-house standard operating procedures, and the legislation in force. Based
      on these sources as well as the hands-on knowledge of the current practice, a
      brief description of the general rules of administrative proceedings involving
      HTA of varying complexity was elaborated. Characteristic features of the
      individual types of proceedings, basic differences in the complexity of HTA
      employed, and its most important challenges were summarized. RESULTS: In Czech
      Republic, HTA in the formal administrative proceedings ensures a transparent
      process of introduction of new medicinal products into clinical practice and
      leaves space for restriction of reimbursement conditions to minimize budget
      impact. CONCLUSIONS: As a robust as well as pragmatic HTA methodology has been
      implemented by SUKL, relevant stakeholders (marketing authorization holders,
      Health Care Funds, clinical expert groups) are now able to influence
      reimbursement of new technologies.

PMID- 28438232
TI  - Real-Life Impact of Executive Function Impairments in Adults Who Were Born Very
      Preterm.
AB  - OBJECTIVES: Children and adolescents who were born very preterm (<=32 weeks'
      gestation) are vulnerable to experiencing cognitive problems, including in
      executive function. However, it remains to be established whether cognitive
      deficits are evident in adulthood and whether these exert a significant effect on
      an individual's real-lifeachievement. METHODS: Using a cross-sectional design, we
      tested a range of neurocognitive abilities, with a focus on executive function,
      in a sample of 122 very preterm individuals and 89 term-born controls born
      between 1979 and 1984. Associations between executive function and a range of
      achievement measures, indicative of a successful transition to adulthood, were
      examined. RESULTS: Very preterm adults performed worse compared to controls on
      measures of intellectual ability and executive function with moderate to large
      effect sizes. They also demonstrated significantly lower achievement levels in
      terms of years spent in education, employment status, and on a measure of
      functioning in work and social domains. Results of regression analysis indicated
      a stronger positive association between executive function and real-life
      achievement in the very preterm group compared to controls. CONCLUSIONS: Very
      preterm born adults demonstrate executive function impairments compared to full
      term controls, and these are associated with lower achievement in several real
      life domains. (JINS, 2017, 23, 381-389).

PMID- 28438233
TI  - miR-126-5p Restoration Promotes Cell Apoptosis in Cervical Cancer by Targeting
      Bcl2l2.
AB  - Cervical cancer is one of the most common cancers in females, with a high
      incidence and mortality around the world. However, the pathogenesis in cervical
      cancer is not completely known. In the present study, we investigated the role of
      miR-126-5p and Bcl2l2 in cervical cancer cells. First, miR-126-5p expression was
      aberrantly downregulated in human cervical cancer tumor tissues in comparison
      with normal tissues, as evaluated by RT-PCR. Consistently, the levels of miR-126
      5p were also significantly reduced in cervical cancer cell lines when compared to
      normal cervical epithelial cells. Flow cytometric analysis showed that the rate
      of apoptosis of cervical cancer cells was significantly increased by miR-126-5p
      overexpression but inhibited by miR-126-5p inhibitor. A similar change pattern
      was observed in the expression of apoptosis-regulated protein caspase 3 in
      cervical cancer cells transfected with miR-126-5p mimic or inhibitor. By
      bioinformatic prediction with online databases and verification using luciferase
      reporter assay, we then identified that Bcl2l2 is a direct target of miR-126-5p
      in cervical cancer cells. The expression of Bcl2l2 was strongly downregulated by
      the miR-126-5p mimic but upregulated by the miR-126-5p inhibitor in cervical
      cancer cells, and Bcl2l2 expression was significantly increased in human cervical
      cancer tumor tissues, which was negatively correlated with miR-126-5p levels.
      Furthermore, we confirmed that the rate of apoptosis was significantly increased
      by Bcl2l2 silencing in cervical cancer cells, which was not affected by the miR
      126-5p inhibitor. In addition, the increased apoptosis of cells by the miR-126-5p
      mimic was inhibited by Bcl2l2 overexpression. In summary, miR-126-5p plays an
      inhibitory role in human cervical cancer progression, regulating the apoptosis of
      cancer cells via directly targeting Bcl2l2. This might provide a potential
      therapeutic target for cervical cancer.

PMID- 28438234
TI  - Significant Radiologic Response of Pancreatic Metastasis After Targeted Therapy
      of Ceritinib (LDK378) for ALK-Rearranged Lung Adenocarcinoma Presenting With
      Hyperglycemia.
AB  - Pancreatic metastasis from non-small cell lung cancer (NSCLC) is usually
      asymptomatic or presents with abdominal pain, acute pancreatitis, or jaundice. A
      lung primary is associated with worse survival compared to pancreatic metastases
      from other organs. Surgical treatment of solitary metastasis to the pancreas from
      NSCLC has been reviewed in several studies, one of which had a notable disease
      free interval. To our knowledge, there are no prior reports of targeted therapy
      of pancreatic metastasis of NSCLC followed by a significant response. Herein we
      report the case of a 31-year-old female with a solitary pancreatic metastasis
      from ALK-rearranged lung adenocarcinoma despite treatment with chemotherapy and
      crizotinib; she presented with symptoms of hyperglycemia. Targeted therapy with
      ceritinib (LDK378) led to symptomatic improvement and a significant radiologic
      response in the lung and pancreas, but not in the brain.

PMID- 28438235
TI  - Deception detection: State of the art and future prospects.
AB  - BACKGROUND: Deception detection has been a longstanding concern throughout human
      history. It has also interested scientists, who have explored psychological and
      behavioral differences between liars and truth tellers, as well as ways to
      improve detection accuracy. METHOD: In recent years, substantial advances have
      been made in the field. Some of these advances are briefly reviewed in the
      current article. RESULTS: A description is provided of (a) research and
      contemporary theories on how people (try to) detect deception; (b) recent
      advances on strategic interviewing to detect deception; (c) the integrative
      findings of recent meta-analyses on systematic verbal lie detection approaches;
      and (d) several important aspects concerning psychophysiological detection of
      deception. Also, some emerging trends and research needs for the future are
      outlined at the end of the article. CONCLUSIONS: Deception detection research is
      a lively and dynamic area of applied psychology that has experienced substantial
      developments in recent times. Much (though not all) of these research efforts
      have focused on developing empirically-based lie-detection procedures to be used
      by practitioners (e.g., the police) in applied settings. A number of new topics
      are just starting to be examined. These novel research avenues will surely yield
      interesting new findings in the future.

PMID- 28438236
TI  - Personal and macro-systemic factors as predictors of quality of life in chronic
      schizophrenia.
AB  - BACKGROUND: The goal of this research was to establish possible predictive
      factors for both subjective and externally assessed quality of life in people
      with chronic schizophrenia. METHODS: Sixty-eight people with schizophrenia took
      part in the study and were assessed using the World Health Organisation Quality
      of Life Assessment - Brief Version (WHOQOL-BREF), the Quality of Life Scale
      (QLS), the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the
      Global Assessment of Functioning (GAF), the Social Functioning Scale (SFS) tests.
      Correlations and multiple regression analysis were conducted to determine
      possible predictors of quality of life. RESULTS: The residential environment
      (rural/urban), diagnosis, age at onset of disorder, global functioning and social
      functioning explained 68% of the total variance based on proxies&rsquo;
      assessment quality of life. Living arrangements and social functioning emerged as
      predictor variables for subjective quality of life, explaining a 47.3% of the
      total variance. CONCLUSIONS: Socio-cultural factors, such as social integration
      or the quality of interpersonal relationships, have more influence on these
      peoples&rsquo; physical and psychological health than certain personal factors,
      such as psychopathology. It is therefore advisable to pay attention to the
      environment and macro-systemic variables when developing intervention plans to
      improve their quality of life.

PMID- 28438237
TI  - Are unwanted mental intrusions a transdiagnostic variable?
AB  - INTRODUCTION: Unwanted mental intrusions (UMI) constitute the normal variants of
      obsessions in Obsessive-Compulsive Disorder (OCD), preoccupations about defects
      in Body Dysmorphic Disorder (BDD), images about illness in Hypochondriasis (HYP),
      and thoughts about eating in Eating Disorders (EDs). We sought to investigate the
      relationships between frequency and discomfort associated with the experience of
      the four UMI contents, adopting a within-subject perspective. METHOD: A group of
      438 university students and community participants (Mage= 29.84, SD= 11.41;
      70.54% women), completed the Questionnaire of Unpleasant Intrusive Thoughts to
      assess the frequency and discomfort of four UMI contents related to OCD, BDD, HYP
      and EDs. RESULTS: Just over 76% of participants reported having experienced the
      four sets of intrusions. The ED-related were the most frequent but the least
      disturbing, whereas HYP intrusions were the least frequent but the most
      disturbing. The four UMI were significantly related to each other, both in
      frequency and discomfort. Women experienced OCD, BDD, and ED-related intrusions
      more frequently than men. Age was negatively associated with the frequency and
      distress of the four UMIs. CONCLUSIONS: UMIs might be a transdiagnostic variable
      across different disorders such as OCD, BDD, EDs, and Hypochondriasis, and they
      might contribute to explaining the phenomenological similarities among them.

PMID- 28438238
TI  - Behavioral activation versus cognitive restructuring to reduce automatic negative
      thoughts in anxiety generating situations.
AB  - BACKGROUND: Recent studies have compared the efficacy of cognitive intervention
      compared to behavioral techniques for the treatment of different disorders. In
      line with that work, the empirical study presented here examined the efficacy of
      Behavioral Activation (BA) and Cognitive Therapy (CT) on Negative Automatic
      Thoughts (PANs) elicited in situations generating anxiety. METHOD: Based on a
      sample of 42 students aged 18 to 21 who took the ISRA B, BADS and EROS, 18
      subjects with the highest scores were selected and assigned at random to one of
      two experimental groups or to a control group. Experimental Group 1 was given
      intervention based on CT and Experimental Group 2 based on BA. Both interventions
      consisted of five 60-min sessions. RESULTS: Pre and post treatment measurement
      analyses reveal that both conditions effectively reduced the intensity of the
      anxiety response. However, BA was the only condition showing a significant
      reduction in ANTs. CONCLUSIONS: The results are discussed stressing the efficacy
      of BA in exclusively cognitive intervention.

PMID- 28438239
TI  - Sex, gender roles and sexual attitudes in university students.
AB  - BACKGROUND: Previous studies usually refer to a greater repertoire of sexual
      behav-iors and a higher level of erotophilia in men than in women. The main goal
      of this work is to relate sex, gender roles and sexual attitudes to sexual
      behavior. METHOD: 411 un-dergraduate students (218 women and 193 men) at theof
      University of Oviedo (Spain) completed the following instruments: the Bem Sex
      Roles Inventory to operationalize the variable gender, the Sexual Inventory which
      reflects sexual behaviors, and the Sexual Opinion Survey about sexual attitudes.
      RESULTS: 27% of the sample was typified as an-drogynous. There are were no
      differences in attitudes, either by sex (p= .50) or by gen-der (p= .77). Sexual
      behaviors depended on the degree of erotophilia (p= .000). CONCLUSIONS: the
      results suggest that, although regarding sex, the fact that women&rsquo;s
      erotophilic attitudes have increased their erotophilic attitudes, although they
      refer to more conventional sexual behaviors than mens&rsquo;s attitudes. With
      regard to gender, a tendency towards androgyny is observed, androgynous women and
      men report positive attitudes towards sexuality. Gender could act as a mediator
      of sexual behavior through the attitudinal component.

PMID- 28438240
TI  - An explanatory model of maths achievement:Perceived parental involvement and
      academic motivation.
AB  - BACKGROUND: Although numerous studies have tried to explain performance in maths
      very few have deeply explored the relationship between different variables and
      how they jointly explain mathematical performance. METHOD: With a sample of 897
      students in 5th and 6th grade in Primary Education and using structural equation
      modeling (SEM), this study analyzes how the perception of parents&rsquo; beliefs
      is related to children&acute;s beliefs, their involvement in mathematical tasks
      and their performance. RESULTS: Perceived parental involvement contributes to the
      motivation of their children in mathematics. Direct supervision of
      students&rsquo; academic work by parents may increase students&rsquo; concerns
      about the image and rating of their children, but not their academic performance.
      In fact, maths achievement depends directly and positively on the parents&rsquo;
      expectations and children&rsquo;s maths self-efficacy and negatively on the
      parents&rsquo; help in tasks and performance goal orientation. CONCLUSIONS:
      Perceived parental involvement contributes to children&rsquo;s motivation in
      maths essentially conveying confidence in their abilities and showing interest in
      their progress and schoolwork.

PMID- 28438241
TI  - Alcohol and psychotropic substance use in female Spanish victims of intimate
      partner violence.
AB  - BACKGROUND: Studies show high use of alcohol among American women who are victims
      of intimate partner violence (IPV), but not in Spanish victims. This study
      examines hazardous drinking, use of psychotropic substances, and the relationship
      with psychopathological symptoms in Spanish women who are victims of IPV. METHOD:
      50 battered women and 50 control women from general population were assessed.
      RESULTS: Hazardous drinking in women victims of IPV (18.4% and 24.5%) was higher
      than in previous Spanish studies, and lower than in controls (no significant
      difference). Women victims of IPV showed a significantly higher use of
      psychotropic medication than controls (40% vs. 20%). For women victims of IPV,
      psychopathological symptoms were not related to use of alcohol, but use of
      psychotropic medication was related to post-traumatic arousal. CONCLUSIONS:
      Results suggest that Spanish women victims of IPV may resort to psychotropic
      medication rather than alcohol to cope with their symptoms.

PMID- 28438242
TI  - Depression and aggressive behaviour in adolescents offenders and non-offenders.
AB  - BACKGROUND: Adolescent behaviour is strongly linked to emotions. The aim of this
      study is 1) analyse the differences between young offenders and non-offenders in
      emotional instability, anger, aggressive behaviour, anxiety and depression, and
      also the differences according to sex; and 2) compare the relation between
      emotional instability and anxiety, depression and aggressive behaviour mediated
      or modulated by anger in both groups. METHOD: participants are 440 adolescents,
      both male and female (15-18 years old). 220 were young offenders from four
      different correctional centres of the Valencia Region. The other 220 participants
      were randomly chosen from ten public and private schools in the Valencia
      metropolitan area. In the Schools the instruments were applied collectively in
      the classroom, with a 50 minutes maximum duration. In the Youth Detention Centre
      the application was carried out in small groups. RESULTS: The structural equation
      model (SEM) carried out on each group, young offenders and non-offenders show a
      relation between the assessed variables. Emotional instability appears strongly
      related with anger in both samples, but anger just predicts depression and
      aggressive behaviour in the offender population. CONCLUSIONS: The results give
      relevant information for treatment and prevention of aggressive behaviour and
      delinquency in teenagers through emotional regulation.

PMID- 28438243
TI  - Factors which motivate the use of social networks by students.
AB  - BACKGROUND: The aim of this research was to identify those factors which motivate
      the use of social networks by 4th year students in Secondary Education between
      the ages of 15 and 18. METHOD: 1,144 students from 29 public and private schools
      took part. The data were analysed using Partial Least Squares Structural Equation
      Modelling technique. RESULTS: Versatility was confirmed to be the variable which
      most influences the motivation of students in their use of social networks. The
      positive relationship between versatility in the use of social networks and
      educational uses was also significant. CONCLUSIONS: The characteristics of social
      networks are analysed according to their versatility and how this aspect makes
      them attractive to students. The positive effects of social networks are
      discussed in terms of educational uses and their contribution to school learning.
      There is also a warning about the risks associated with misuse of social
      networks, and finally, the characteristics and conditions for the development of
      good educational practice through social networks are identified.

PMID- 28438244
TI  - Exploration of glycaemic states in children with type 1 diabetes.
AB  - BACKGROUND: The prevention of severe hypoglycaemia is based in art on accurately
      anticipating its occurrence. The aim of the study was to analyse the effect of a
      feedback procedure on the glycaemic state of children with type 1 diabetes,
      aswell as the associated symptoms and estimated BGL. METHOD: For 7 days, 17
      participants performed both scheduled capillary blood tests, and an estimate and
      self-analysis whenever they thought that there were changes in their BGL.
      RESULTS: A total of 454 trials were analysed with a mean of 178 mg/dl (SD= 36.4).
      Only 5.1% of the estimates corresponded to hypoglycaemia states, 36.77% were in
      areas with clinically dangerous consequences and were more accurate when the BGL
      reached the levels of <= 56 mg/dl and less accurate when it reached >240 mg/dl.
      The children reported symptoms at random, made mistakes when linking them with
      the BGL and demanded opportunity feedback believing they were in state of
      hypoglycaemia, while being in hyperglycaemia. CONCLUSIONS: The BGL was highly
      variable, certain glycaemic profiles peaked, with a greater average of
      hypoglycaemia than in the children&rsquo;s usual daily surroundings and did not
      present a profile of reliable signs indicative of BGL. The tendency to
      underestimate values when glycaemia was in hyperglycaemic levels is confirmed.

PMID- 28438245
TI  - Bullying and the detrimental role of un-forgiveness in adolescents' wellbeing.
AB  - BACKGROUND: Many studies have shown that victimisation by bullies is linked with
      psychopathology. Research has also demonstrated that forgiveness is associated
      with the mental health of victims of bullying. METHOD: Our objective was to
      explore the multiple components of forgiveness (i.e., benevolence, decreased
      avoidance of the perpetrator and diminished desire for revenge) as mediators of
      the negative mental health effects of bullying in Italian adolescents. Our
      hypothesis was that those who forgive their bullies would show lower levels of
      depression, state anger, and behaviour problems than those who did not forgive.
      Participants were 319 students ages 14 to 22 from two schools in Southern Italy
      who completed five self-report questionnaires measuring levels of victimisation,
      forgiveness, depression, anger, and total behaviour problems. RESULTS: The
      results varied according to the components of forgiveness: although benevolence
      toward the victim was not a significant correlate of outcome, harbouring a desire
      for revenge and avoiding the perpetrator emerged as very maladaptive.
      CONCLUSIONS: Our study indicates that is it important for those working with
      adolescents to help victims of bullying overcome the negative mental health
      effects of the victimisation by letting go of un-forgiveness.

PMID- 28438246
TI  - Does dual-task coordination performance decline in later life?
AB  - BACKGROUND: This cross-sectional study examined whether changes occur in
      people&rsquo;s capacity to coordinate two simultaneous tasks (dual-task) when
      transitioning from adulthood to later life. The central executive,
      Baddeley&rsquo;s working memory model component, is responsible for this
      coordination. Contradictory results have been reported regarding the relationship
      between ageing and dual-task performance; but these seem to be related to
      methodological issues that have been addressed in this study. METHODS: Nine
      hundred and seventy-two participants, aged between 35 and 90 years old,
      volunteered to carry out a verbal digit span task, followed by single and
      concurrent (dual-task) tests: first, a box crossing task, then, the digit recall
      task in relation to their memory span, and finally, both these tests
      simultaneously. RESULTS: We found no difference in people&rsquo;s capacity to
      coordinate their attention when doing two tasks in adulthood or healthy later
      life, including those in the oldest age groups. Furthermore, gender and
      educational level were not related to dual-task performance. CONCLUSIONS: The
      results support the normal functioning of the central executive in very old
      people. These data contrast with research with patients suffering from different
      types of dementia, which show a decrease in their dual-task performance.

PMID- 28438247
TI  - The utility of the Alcohol Use Disorders Identification Test (AUDIT)for the
      analysis of binge drinking in university students.
AB  - BACKGROUND: The increasingly precise conceptualization of Binge Drinking (BD),
      along with the rising incidence of this pattern of intake amongst young people,
      make it necessary to review the usefulness of instruments used to detect it.
      Little evidence exists regarding effectiveness of the AUDIT, AUDIT-C and AUDIT-3
      in the detection of BD. This study evaluates their utility in a sample of
      university students, revealing the most appropriate cut-off points for each sex.
      METHODS: All students self-administered the AUDIT and completed a self-report of
      their alcohol consumption. A Two-step cluster analysis differentiated 5 groups of
      BD in terms of: the quantity consumed, the frequency of BD over the past six
      months and gender. A ROC curve adjusted cut-off points for each case. RESULTS:
      862 university students (18-19 years-old/59.5% female), 424 (49.2%) from Valencia
      and 438 (50.8%) from Madrid, had cut-off points of 4 in AUDIT and 3 in AUDIT-C as
      a better fit. In all cases, the best classifier was AUDIT-C. Neither version
      properly classifies students with varying degrees of BD. CONCLUSIONS: All
      versions differentiate BD from non-BD, but none are able to differentiate between
      types of BD.

PMID- 28438248
TI  - Program FACTOR at 10: Origins, development and future directions.
AB  - BACKGROUND: We aim to provide a conceptual view of the origins, development and
      future directions of FACTOR, a popular free program for fitting the factor
      analysis (FA) model. METHOD: The study is organized into three parts. In the
      first part we discuss FACTOR in its initial period (2006-2012) as a traditional
      FA program with many new and cutting-edge features. The second part discusses the
      present period (2013-2016) in which FACTOR has developed into a comprehensive
      program embedded in the framework of structural equation modelling and item
      response theory. The third part discusses expected future developments. RESULTS:
      at present FACTOR has attained a degree of technical development comparable to
      commercial software, and offers options not available elsewhere. DISCUSSION: We
      discuss several shortcomings as well as points that require changes or
      improvements. We also discuss the functioning of FACTOR within its community of
      users.

PMID- 28438249
TI  - The Acceptance of Dating Violence scale (ADV): Psychometric properties of the
      Spanish version.
AB  - BACKGROUND: The main aim of this study was to analyse the psychometric properties
      of the Spanish version of the Acceptance of Dating Violence (ADV) scale, which
      assesses attitudes that justify the use of aggression in adolescents&rsquo;
      dating relationships. METHOD: A total of 1,579 high school students (49% girls)
      from Bizkaia (Spain), aged between 14 and 18 years (M = 15.79, SD = 1.16),
      completed this questionnaire along with the Irrational Beliefs Scale for
      Adolescents and the Conflict in Adolescent Dating Relationships Inventory.
      RESULTS: The factor analyses suggested a one-factor structure, which fits data
      well for both girls and boys. Moreover, the ADV showed good internal consistency
      (&alpha; = .83) and was related to general justification of violence and dating
      violence (perpetration and victimization). Boys (compared to girls) and
      adolescents who had had a dating relationship in the past year (compared to those
      who had not) displayed a higher acceptance of dating violence. CONCLUSIONS: The
      ADV is a useful, brief and easily applicable instrument for the assessment of
      attitudes toward dating violence.

PMID- 28438250
TI  - New validity evidence of the Parent PARQ/Control scale of Parental Educational
      Styles.
AB  - BACKGROUND: The Parent PARQ/Control (short version) for mothers and fathers is an
      inventory of 29 items where parents record their acceptance-rejection and control
      behaviors towards their children. Despite vast research on IPARQTheory, it has
      yet to be vali-dated for a Spanish population. The goal of this study is to
      analyze the psychometric properties of the instrument and its factorial
      structure. METHOD: Participants were 4,168 parents from the Principality of
      Asturias (2,166 mothers and 2,002 fathers). Mean age for mothers was 39.50 years
      and 41.90 years for fathers. Following preliminary studies, we carried out
      exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) for
      mothers and for fathers separately. RESULTS: Analysis of mothers&rsquo; responses
      reveal an instrument comprising 15 items with a three factor-structure:
      warmth/affection, hostility/aggression and control. For fathers, the structure of
      the inventory gave a 23 item instrument with four factors: warmth/affection,
      hostility/aggression, indifference/neglect and control. CONCLUSIONS: Overall,
      these results show that warmth/affection and control are the main dimensions in
      parental educational styles, and as hypothesized, mothers and fathers have
      different educational styles.

PMID- 28438251
TI  - The short form of the VIA Inventory of Strengths.
AB  - BACKGROUND: The VIA Institute on Character is offering the VIA-120 as the
      standard VIA Survey, replacing the original 240-item version. The present work
      involved the construction and the initial evaluation of the Spanish VIA-120 as a
      short version of the Spanish adaptation of the VIA-IS. METHOD: This short form
      was developed using data from 2,143 Spanish-speaking adults. The Spanish VIA-120
      was developed by selecting the five items with the highest corrected item-total
      correlations from the 10 items per subscale of the Spanish VIA-IS. RESULTS:
      Results lent support to the reliability and validity of this short form to
      measure the 24 character strengths included in The Values in Action (VIA)
      classification. The internal consistency coefficients of the subscales of the
      Spanish version of the VIA-120 were substantially equivalent to the long version.
      The VIA-120 showed high convergence with the Spanish VIA-IS in terms of
      descriptive statistics and associations with life satisfaction, positive affect,
      and negative affect. Factor structure congruence coefficients also indicated very
      high convergence between the VIA-IS and the short form. CONCLUSIONS: The Spanish
      VIA-120 proved to be a reliable, valid instrument for the assessment of character
      strengths.

PMID- 28438252
TI  - An exploratory sequential design to validate measures of moral emotions.
AB  - BACKGROUND: This paper presents an exploratory and sequential mixed methods
      approach in validating measures of knowledge of the moral emotions of contempt,
      anger and disgust. METHOD: The sample comprised 60 participants in the
      qualitative phase when a measurement instrument was designed. Item stems,
      response options and correction keys were planned following the results obtained
      in a descriptive phenomenological analysis of the interviews. In the quantitative
      phase, the scale was used with a sample of 102 Spanish participants, and the
      results were analysed with the Rasch model. RESULTS: In the qualitative phase,
      salient themes included reasons, objects and action tendencies. In the
      quantitative phase, good psychometric properties were obtained. The model fit was
      adequate. However, some changes had to be made to the scale in order to improve
      the proportion of variance explained. CONCLUSIONS: Substantive and methodological
      im-plications of this mixed-methods study are discussed. Had the study used a
      single re-search method in isolation, aspects of the global understanding of
      contempt, anger and disgust would have been lost.

PMID- 28438253
TI  - Development and validation of the Work Conflict Appraisal Scale (WCAS).
AB  - BACKGROUND: In the context of cognitive appraisal, the Work Conflict Appraisal
      Scale (WCAS) was developed to assess work conflict in terms of threat and
      challenge. METHOD: In the first study, the factorial structure of the scale was
      tested using confirmatory factor analysis with a Spanish multi-occupational
      employee sample (N= 296). In the sec-ond study, we used multi-sampling
      confirmatory factor analysis (N= 815) to cross-validate the results. RESULTS: The
      analyses confirm the validity of the scale and are con-sistent with the tri
      dimensional conflict classification. The findings support the distinc-tion
      between the challenge and threat appraisals of work conflict, highlighting the im
      portance of measuring these two types of appraisal separately. CONCLUSIONS: This
      scale is a valid and reliable instrument to measure conflict appraisal in
      organizations.

PMID- 28438254
TI  - Validity and reliability of the Spanish version of the Somatoform Dissociation
      Questionnaire (SDQ-20).
AB  - BACKGROUND: The Somatoform Dissociation Questionnaire (SDQ-20) is a self-reported
      questionnaire measuring somatoform dissociation. The aim of this study is to
      analyze the psychometric properties of the Spanish version of the SDQ-20 and its
      short version (SDQ-5). METHODS: Validity and reliability were examined in a
      sample of 360 psychiatric outpatients: 38 dissociative (conversion) disorders, 30
      dissociative (psychoform) disorders, and 292 patients suffering from other
      disorders. Dissociative disorders were diagnosed using the SCID-D and a specific
      interview for conversion disorders. RESULTS: Subjects meeting criteria for any
      dissociative or conversion disorder scored significantly higher in the SDQ-20
      (criterion validity). Somatoform dissociation, psychoform dissociation and early
      trauma were significantly correlated (construct validity). An alpha coefficient
      of .866 (reliability) and a test-retest correlation of 0.91 were obtained. The
      cut-off score maximizing sensitivity and specificity was 27.5 for psychoform
      dissociative disorders (sensitivity of 81.6% and specificity of 71.0%) and 29.5
      for conversion disorders (81.6% and 71.0%). For the SDQ-5, the coefficient alpha
      was 0.561 and the selected cut-off score was 5.5 (sensitivity of 73.33% and
      specificity of 70.41%). CONCLUSIONS: The Spanish version of the SDQ-20 presents
      good psychometric properties while the SDQ-5 shows worse characteristics and its
      use with Spanish samples is not recommended.

PMID- 28438255
TI  - A strategy based on patient preference improves the adherence and outcomes of
      phosphate binders in hemodialysis?.
AB  - PURPOSE: Phosphate binders (PB) have to be taken with food, their interference
      with an individual's lifestyle and social habits influences treatment adherence.
      Several PBs are available, and patient preferences should not be ignored when
      prescribing. The purpose was to know the extent of intentional and unintentional
      nonadherence to PB in hemodialysis (HD) patients, and to evaluate the long-term
      results (adherence, serum phosphate levels, and cost) of a strategy of
      prescription of PB that takes into account patient preferences. PATIENTS AND
      METHODS: A prospective open-label, single-arm study, conducted in all 130
      prevalent HD patients of our unit. Each patient was compared with themselves
      before (baseline) and 6, 12, and 24 months after adopting the new strategy.
      Factors included in the decision tree to prescribe PB were patient preferences,
      cost, and security. Self-reported, intentional, and unintentional nonadherence,
      serum P levels, and cost were evaluated. Patients were instructed to request a
      change of PB if they had problems or did not like those prescribed.
      <u>Results:</u> After implementing the new strategy, the percentage of patients
      receiving calcium PB monotherapy increased (p < 0.001), while the percentage of
      those receiving noncalcium PB monotherapy (p < 0.001) and a combination of
      noncalcium PB (p < 0.01) decreased. Self-reported nonadherence (64.6%) and
      intentional nonadherence (38.4%) decreased significantly at 6 months and remained
      stable until the end of the study (50.6%; p < 0.05 and 24.9%; p < 0.01,
      respectively). Unintentional nonadherence did not change. Intentionally
      nonadherent patients at baseline showed a significant and maintained decrease of
      serum P levels (p < 0.05) and in the number of tablets/day of PB (p < 0.01).
      Implementing the protocol resulted in a significant reduction of costs expended
      in PB. CONCLUSION: Individualization of treatment that takes into account patient
      preferences improves the adherence and control of P levels at a lower cost. The
      most important changes after the new strategy were observed in intentionally
      nonadherent patients.?.

PMID- 28438256
TI  - Clinical profile and outcome of patients with biopsy-proven acute interstitial
      nephritis in Cape Town: a 10-year review?.
AB  - BACKGROUND: Acute interstitial nephritis (AIN) is a common cause of acute kidney
      injury that has not been adequately characterized in Sub-Saharan Africa (SSA)
      despite an increasing use of potentially inciting agents for the treatment of
      human immunodeficiency virus (HIV) and tuberculosis in the region. METHODS: A
      retrospective audit of records of patients with biopsy-proven AIN diagnosed at
      Groote Schuur Hospital, Cape Town from the 1<sup>st</sup> of January, 2006, to
      the 31<sup>st</sup> of December, 2015. RESULTS: 54 patients with biopsy-proven
      AIN were reviewed. The majority were of black African origin (59.2%), with HIV
      (42.8%) and HIV-tuberculosis coinfection (30.5%) as the most common
      comorbidities. Drug-related AIN was seen in 38 (67.9%) patients, with rifampicin
      as the most often implicated medication. Probable drug-related AIN was seen in 3
      (5.4%) patients, infection-related AIN in 8 (14.3%), and unspecified causes in 4
      (7.4%). AIN was suspected in 44.6% of patients before biopsy. 18 patients (34%)
      received hemodialysis, while 19 (35.2%) were treated with corticosteroids.
      Complete renal recovery at 30 and 90 days was seen in 23 (42.6%) patients and 24
      (45.3%) patients, respectively, with the majority seen among those with drug
      induced AIN. Six (11.1%) patients died; 4 (10.5%) of the patients were in the
      drug-related group. There was no correlation between degree of interstitial
      inflammation and severity of renal failure (p = 0.10). On multivariate logistic
      regression, drug-related causes of AIN were predictive of complete recovery at
      day 30 (OR 16.63; 95% CI: 1.71 - 161.6, p = 0.02), and presence of interstitial
      fibrosis reduced likelihood of recovery (OR 0.03; 95% CI 0.002 - 0.46, p =
      0.012). Steroid use did not influence partial recovery (OR 0.59, 95% CI 0.17 -
      1.77; p = 0.32) or complete recovery (OR 3.38, 95% CI 0.38 - 30.39, p = 0.28).
      CONCLUSIONS: AIN is common in patients with HIV or those on treatment for
      tuberculosis. Drug-related AIN is often associated with improved outcomes. This
      is particularly reassuring in the SSA region where the use of potentially
      inciting medications is rife from a high burden of HIV and tuberculosis.?.

PMID- 28438257
TI  - Pharmacokinetics and relative bioavailability of two allopurinol tablets in
      healthy Chinese volunteers?.
AB  - OBJECTIVE: To evaluate the pharmacokinetics and relative bioavailability of two
      allopurinol tablets in healthy Chinese volunteers. METHODS: A single-center,
      randomized, cross-over, two-period study design was conducted in healthy male
      subjects who were identified as not carrying the HLA-B*58:01 allele. Under
      fasting conditions, a single oral dose of 300 mg test or reference tablets was
      given with a 1-week washout period. The blood samples were collected for up to 12
      hours after the administration and the plasma concentrations of allopurinol were
      determined by high performance liquid chromatography. Subject interviews and
      physical examinations were done over regular intervals to monitor the adverse
      events. RESULTS: 18 subjects were enrolled in the study, and none dropped out.
      The main pharmacokinetic parameters of allopurinol test and reference
      preparations were as follows: AUC<sub>0-tlast</sub> was 6,725.1 +/- 1,390.0
      ng*h*mL<sup>-1</sup> and 6,425.6 +/- 1,257.6 ng*h*mL<sup>-1</sup>; AUC<sub>0
      infinity</sub> was 7,069.1 +/- 1,503.2 ng*h*mL<sup>-1</sup> and 6,750.6 +/-
      1,347.7 ng*h*mL<sup>-1</sup>; t<sub>max</sub> was 1.3 +/- 0.8 hours and 1.3 +/-
      0.8 hours; C<sub>max</sub> was 2,203.7 +/- 557.4 ng*mL<sup>-1</sup> and 2,310.8
      +/- 662.8 ng*mL<sup>-1</sup>; and T<sub>1/2</sub> was 2.0 +/- 1.6 hours and 1.7
      +/- 0.7 hours. The relative bioavailability was 105.1 +/- 12.6%. The 90%
      confidence intervals for the geometric mean ratios (test/reference) of
      C<sub>max</sub>, AUC<sub>0-tlast</sub>, and AUC<sub>0-infinity</sub> of both
      preparations fell within the bioequivalence acceptance criteria (80 - 125%). No
      adverse events were found or reported during the study. CONCLUSION: The test
      allopurinol preparations and the reference preparations are bioequivalent and
      both are well tolerated.?.

PMID- 28438258
TI  - Intraneural glomus tumor of "uncertain malignant potential" and with BRAF
      mutation in the median nerve - an unusual case.
AB  - A glomus tumor of uncertain malignant potential is defined as a glomus tumor with
      some, but not all, criteria for malignancy and without a known metastasis. Here,
      we present a rare example presenting in the median nerve in a 40-year-old woman
      with a long history of severely impaired left median nerve function. A large
      panel of immunohistochemical stains excluded other diagnoses, and the designation
      of a "uncertain malignant potential" was based on the high proliferative
      activity, the tumor size and location, and the lack of WHO malignancy criteria
      such as marked nuclear atypia, necrosis, or atypical mitoses. A BRAF mutation was
      found in the tumor. Although extremely rare, both benign and malignant glomus
      tumors may present in large peripheral nerves and should therefore be considered
      in the differential diagnosis.?.

PMID- 28438260
TI  - More is better: Lymph node harvesting in colorectal cancer.
AB  - INTRODUCTION: We sought to determine if lymph node harvesting and survival for
      CRC were comparable between laparoscopic and open resections in a community
      hospital setting. METHODS: A retrospective chart review of patients at two
      community hospitals who underwent open or laparoscopic resection for CRC between
      January 2008 and September 2013 was performed. RESULTS: Three hundred seventy-one
      patients had open and 110 had laparoscopic resections. There was no difference
      between open (17.85) and laparoscopic (18.91) approaches (p = 0.171) in the
      number of lymph nodes harvested. Patients who had more nodes removed tended
      toward improved survival, independent of stage (p = 0.052), an effect that was
      more pronounced in the open resection group (p = 0.031). There was no difference
      in survival between the open and laparoscopic groups overall (HR 1.52, p =
      0.208). DISCUSSION: No survival advantage was found between the open and
      laparoscopic resection groups, affirming that the choice of operative approach
      for CRC does not affect the quality of the oncologic procedure in a community
      hospital setting. Patients who had more lymph nodes removed tended toward
      improved survival. The explanation for this effect remains unclear.

PMID- 28438261
TI  - The Affordable Care Act and its association with length of stay and payer status
      for trauma patients at a level I trauma center.
AB  - BACKGROUND: We hypothesized that the ACA would shorten length of stay and
      increase numbers of insured patients without changing trauma patient outcomes.
      METHODS: A retrospective review of adult trauma patients admitted to a level I
      trauma center between 2012 and 2014 was performed. Demographics, length of stay,
      payer status, discharge disposition, and complications before and after the ACA
      implementation were analyzed. RESULTS: 4448 trauma patients were admitted during
      the study period. Patients treated after ACA implementation were older (53 vs 51,
      p = 0.05) with shorter ICU stays (1.7 vs 1.5 days, p = 0.04), but longer overall
      hospital stays (3.7 vs 4.1 days, p < 0.01). The proportion of self-pay patients
      decreased 11%-3% (p=<0.001). A higher proportion of patients were discharged to
      skilled nursing facilities (SNF, 17.1% vs 19.9%, p = 0.02). There was no change
      in rates of death, readmission, infection, pneumonia or decubiti. CONCLUSION:
      Among trauma patients, there was a decrease in self-pay status and increase in
      public insurance without change in private insurance after implementation of the
      ACA. More patients were discharged to SNF without changes in reported outcomes.

PMID- 28438263
TI  - Cutaneous Angiosarcoma: The Importance of Clinical Suspicion.

PMID- 28438262
TI  - Hair-follicle Transplant Into Chronic Ulcers: A New Graft Concept.
AB  - Chronic venous leg ulcers are a major therapeutic challenge in clinical practice,
      and the search for new approaches to improve wound healing is essential. Many
      ulcers do not heal with traditional treatment using compression, debridement, and
      dressings. Skin-grafts variants, such as pinch grafts, punch grafts, split- or
      full-thickness skin grafts, and grafts derived from cells cultured in the
      laboratory, are among the most widely used options in ulcers that do not heal. In
      recent years, numerous studies have brought to our attention the important role
      of the hair follicle in the healing process of cutaneous wounds. Putting
      knowledge into practice, hair follicles from the scalp have been used in punch
      type grafts transplanted to the base of chronic ulcers to stimulate healing.
      Results appear to be better than those with traditional hairless punch grafts,
      opening new lines of treatment for recalcitrant chronic venous ulcers.

PMID- 28438259
TI  - Variation in olfactory neuron repertoires is genetically controlled and
      environmentally modulated.
AB  - The mouse olfactory sensory neuron (OSN) repertoire is composed of 10 million
      cells and each expresses one olfactory receptor (OR) gene from a pool of over
      1000. Thus, the nose is sub-stratified into more than a thousand OSN subtypes.
      Here, we employ and validate an RNA-sequencing-based method to quantify the
      abundance of all OSN subtypes in parallel, and investigate the genetic and
      environmental factors that contribute to neuronal diversity. We find that the OSN
      subtype distribution is stereotyped in genetically identical mice, but varies
      extensively between different strains. Further, we identify cis-acting genetic
      variation as the greatest component influencing OSN composition and demonstrate
      independence from OR function. However, we show that olfactory stimulation with
      particular odorants results in modulation of dozens of OSN subtypes in a subtle
      but reproducible, specific and time-dependent manner. Together, these mechanisms
      generate a highly individualized olfactory sensory system by promoting neuronal
      diversity.

PMID- 28438264
TI  - Vasculitis With Lesions on the Scalp as the Only Cutaneous Manifestation.

PMID- 28438265
TI  - Autoinflammatory Diseases in Pediatric Dermatology-Part 2: Histiocytic,
      Macrophage Activation, and Vasculitis Syndromes.
AB  - The discovery of new autoinflammatory syndromes and novel mutations has advanced
      at breakneck speed in recent years. Part 2 of this review focuses on vasculitis
      syndromes and the group of histiocytic and macrophage activation syndromes. We
      also include a table showing the mutations associated with these autoinflammatory
      syndromes and treatment alternatives.

PMID- 28438266
TI  - Physiological Role of Two-Component Signal Transduction Systems in Food
      Associated Lactic Acid Bacteria.
AB  - Two-component systems (TCSs) are widespread signal transduction pathways mainly
      found in bacteria where they play a major role in adaptation to changing
      environmental conditions. TCSs generally consist of sensor histidine kinases that
      autophosphorylate in response to a specific stimulus and subsequently transfer
      the phosphate group to their cognate response regulators thus modulating their
      activity, usually as transcriptional regulators. In this review we present the
      current knowledge on the physiological role of TCSs in species of the families
      Lactobacillaceae and Leuconostocaceae of the group of lactic acid bacteria (LAB).
      LAB are microorganisms of great relevance for health and food production as the
      group spans from starter organisms to pathogens. Whereas the role of TCSs in
      pathogenic LAB (most of them belonging to the family Streptococcaceae) has
      focused the attention, the roles of TCSs in commensal LAB, such as most species
      of Lactobacillaceae and Leuconostocaceae, have been somewhat neglected. However,
      evidence available indicates that TCSs are key players in the regulation of the
      physiology of these bacteria. The first studies in food-associated LAB showed the
      involvement of some TCSs in quorum sensing and production of bacteriocins, but
      subsequent studies have shown that TCSs participate in other physiological
      processes, such as stress response, regulation of nitrogen metabolism, regulation
      of malate metabolism, and resistance to antimicrobial peptides, among others.

PMID- 28438267
TI  - The Arsenic Detoxification System in Corynebacteria: Basis and Application for
      Bioremediation and Redox Control.
AB  - Arsenic (As) is widespread in the environment and highly toxic. It has been
      released by volcanic and anthropogenic activities and causes serious health
      problems worldwide. To survive arsenic-rich environments, soil and saprophytic
      microorganisms have developed molecular detoxification mechanisms to survive
      arsenic-rich environments, mainly by the enzymatic conversion of inorganic
      arsenate (AsV) to arsenite (AsIII) by arsenate reductases, which is then extruded
      by arsenite permeases. One of these Gram-positive bacteria, Corynebacterium
      glutamicum, the workhorse of biotechnological research, is also resistant to
      arsenic. To sanitize contaminated soils and waters, C. glutamicum strains were
      modified to work as arsenic "biocontainers." Two chromosomally encoded ars
      operons (ars1 and ars2) are responsible for As resistance. The genes within these
      operons encode for metalloregulatory proteins (ArsR1/R2), arsenite permeases
      (Acr3-1/-2), and arsenate reductases (ArsC1/C2/C1'). ArsC1/C2 arsenate reductases
      are coupled to the low molecular weight thiol mycothiol (MSH) and to the recently
      discovered mycoredoxin-1 (Mrx-1) present in most Actinobacteria. This MSH/Mrx-1
      redox system protects cells against different forms of stress, including reactive
      oxygen species (ROS), metals, and antibiotics. ROS can modify functional sulfur
      cysteines by oxidizing the thiol (-SH) to a sulfenic acid (-SOH). These oxidation
      sensitive protein cysteine thiols are redox regulated by the MSH/Mrx-1 couple in
      Corynebacterium and Mycobacterium. In summary, the molecular mechanisms involved
      in arsenic resistance system in C. glutamicum have paved the way for
      understanding the cellular response against oxidative stress in Actinobacteria.

PMID- 28438268
TI  - Fungal Biorecovery of Gold From E-waste.
AB  - Waste electric and electronic devices (e-waste) represent a source of valuable
      raw materials of great interest, and in the case of metals, e-waste might become
      a prized alternative source. Regarding gold, natural ores are difficult to mine
      due to their refractory nature and the richest ores have almost all been
      exploited. Additionally, some gold mining areas are present in geopolitically
      unstable regions. Finally, the gold mining industry produces toxic compounds,
      such as cyanides. As a result, the gold present in e-waste represents a
      nonnegligible resource (urban mining). Extraction methods of gold from natural
      ores (pyro- and hydrometallurgy) have been adapted to this particular type of
      matrix. However, to propose novel approaches with a lower environmental
      footprint, biotechnological methods using microorganisms are being developed
      (biometallurgy). These processes use the extensive metabolic potential of
      microbes (algae, bacteria, and fungi) to mobilize and immobilize gold from urban
      and industrial sources. In this review, we focus on the use of fungi for gold
      biomining. Fungi interact with gold by mobilizing it through mechanical attack as
      well as through biochemical leaching by the production of cyanides. Moreover,
      fungi are also able to release Au through the degradation of cyanide from
      aurocyanide complexes. Finally, fungi immobilize gold through biosorption,
      bioaccumulation, and biomineralization, in particular, as gold nanoparticles.
      Overall, the diversity of mechanisms of gold recycling using fungi combined with
      their filamentous lifestyle, which allows them to thrive in heterogeneous and
      solid environments such as e-waste, makes fungi an important bioresource to be
      harnessed for the biorecovery of gold.

PMID- 28438269
TI  - Stone-Eating Fungi: Mechanisms in Bioweathering and the Potential Role of
      Laccases in Black Slate Degradation With the Basidiomycete Schizophyllum commune.
AB  - Many enzymes, such as laccases, are involved in the saprotrophic lifestyle of
      fungi and the effects of those may be linked to enhanced bioweathering on stone
      surfaces. To test this hypothesis, we studied the decomposition of kerogen
      enriched lithologies, especially with black slate containing up to 20% of Corg.
      Indeed, a formation of ditches with attached hyphal material could be observed.
      To address enzymes involved, proteomics was performed and one group of enzymes,
      the multicopper oxidase family members of laccases, was specifically
      investigated. A role in bioweathering of rocks containing high contents of
      organic carbon in the form of kerogen could be shown using the basidiomycete
      Schizophyllum commune, a white rot fungus that has been used as a model organism
      to study the role of filamentous basidiomycete fungi in bioweathering of black
      slate.

PMID- 28438270
TI  - Innovation within a national health care system.
AB  - Tony is a practicing frontline National Health Service surgeon and director of
      medical innovation at Anglia Ruskin University and has founded 4 medical
      technology start-ups. He has also cofounded the L500 million Anglia Ruskin
      MedTech Campus, which will become one of the world's largest health innovation
      spaces. In 2014, he was appointed as national clinical director for innovation at
      National Health Service England and in February 2016 became the first national
      clinical lead for innovation. In this role, he provides clinical leadership and
      support in delivering improved health outcomes in England, drives the uptake of
      proven innovations across the National Health Service, promotes economic growth
      through innovation, and helps make the National Health Service the go-to place on
      the planet for medical innovation.

PMID- 28438271
TI  - How does an inventor find an investor or partner? Raising funds to start a
      company.
AB  - Rudy Mazzocchi has over 25 years of senior executive management, technology and
      intellectual property development, and financing experience in the medical
      technology/biotechnology industries. He serves currently as cofounder/chief
      executive officer of ELENZA, Inc, an ophthalmology company that has developed an
      electro-active, autofocusing, implantable lens; executive chairman of
      Establishment Labs; executive chairman of LAFORGE Optical; and executive chairman
      of OptiSTENT, Inc. He served previously as managing director of Accuitive Medical
      Ventures and The Innovation Factory; cofounder/chief executive officer of Image
      Guided NEUROLOGICS, acquired by Medtronic in 2005; and founding chief executive
      officer of MICROVENA Corporation, which became "eV3," acquired by Covidien. He
      was formerly cofounder/director of Vascular Science, acquired by St Jude Medical
      in 1996, and cofounder/chairman of CytoGenesis, one of the first United States
      stem cell companies that was merged with BresaGen and listed on the Australian
      public exchange. He is the recipient of the Technology Leadership Award, the
      Businessman of the Year Award, the Ernst & Young Entrepreneur of the Year Award
      in Healthcare, and Global Entrepreneur of the Year Award. He has also authored
      more than 70 patents; 2 published, award-winning novels (medical thrillers); and
      a top-selling business book on entrepreneurism.

PMID- 28438272
TI  - Inspiration, perspiration, and execution: An innovator's perspective.
AB  - Josh Makower, MD, is a General Partner at New Enterprise Associates, Consulting
      Professor of Medicine at Stanford University Medical School, Co-Founder of
      Stanford's Biodesign Innovation Program, and Founder and Executive Chairman of
      the medical device incubator, ExploraMed Development, LLC.

PMID- 28438273
TI  - Yoga during pregnancy: The effects on labor pain and delivery outcomes (A
      randomized controlled trial).
AB  - OBJECTIVE: To investigate the effects of an antenatal yoga program on perceived
      maternal labor pain and delivery outcomes. MATERIAL & METHODS: This randomized
      control trial was conducted with sixty primiparous women, aged 18-35 years old,
      who were randomly assigned to either an antenatal yoga program or control groups.
      Labor pain and discomfort level of the participants were measured using a Visual
      Analogue Scale at cervical dilatation of 3-4 c and at 2 and 4 h after the initial
      measurement. Demographic and obstetrical information were collected. The
      antenatal yoga program consisted of a 1-h supervised yoga class, three times a
      weekly, starting at 26 weeks gestation. . RESULTS: Participants in control group
      reported higher pain intensity compared to experimental group at 3-4 cm of
      dilatation (p = 0.01) and at 2 h after the first and the second measurements (p =
      0.000). Mothers in the antenatal intervention group that completed the yoga class
      required a decreased frequency of labor induction in comparison with control
      group (p = 0.008). In addition, mode of delivery of the intervention group
      resulted in a lower percentage of cesarean section than control group (p =
      0.002). Lastly, the intervention group experienced a shorter duration of the
      second and third stages of labor. Interval level data was analyzed by using an
      independent t-test and chi-square. CONCLUSION: Yoga during pregnancy may
      contribute to a reduction pain of labor and improved adequacy of childbirth.

PMID- 28438274
TI  - The effectiveness of acupuncture, acupressure and chiropractic interventions on
      treatment of chronic nonspecific low back pain in Iran: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Low back pain (LBP) is one of the most common health problems in
      adults. The impact of LBP on the individual can cause loss of health status and
      function related to pain in the back. To reduce the impact of LBP on adults, drug
      therapy is the most frequently recommended intervention. But over the last
      decade, a substantial number of randomized clinical trials of non-pharmacological
      intervention for LBP have been published. OBJECTIVE: To determine the
      effectiveness of acupuncture, acupressure and chiropractic (non-pharmacological)
      interventions on the treatment of chronic nonspecific low back pain in Iran.
      STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic
      literature search was completed without date restrictions up to May 2013 in five
      major databases (Medline, CINAHL, Science Direct, CAJ Full-text Database, and
      Cochrane databases). Only randomized controlled trials published in Persian
      (Farsi) or English languages were included. Two independent reviewers extracted
      the data. The quality of the papers was assessed using the Cochrane Back Review
      Risk of Bias criteria. RESULTS: Initial searches revealed 415 papers, 382 of
      which were excluded on the basis of abstract alone. After excluding 23 papers due
      to duplication, the remaining 10 trial papers were subjected to a more detailed
      analysis of the full text, which resulted in three being excluded. The seven
      remaining trials had a lack of methodological and clinical homogeneity,
      precluding a meta-analysis. The trials used different comparators with regards to
      the primary outcomes, the number of treatments, the duration of treatment and the
      duration of follow-up. CONCLUSION: This systematic review demonstrates that
      acupuncture, acupressure and chiropractic may have a favorable effect on self
      reported pain and functional limitations on NSCLBP. However, the results should
      be interpreted in the context of the limitations identified, particularly in
      relation to the heterogeneity in the study characteristics and the low
      methodological quality in many of the included studies.

PMID- 28438275
TI  - Psychophysical health status of breast cancer survivors and effects of 12 weeks
      of aerobic training.
AB  - The aim of this study was to analyse the health status of breast cancer survivors
      and the effects of 12 weeks of aerobic training. Twenty-three breast cancer
      survivors (51.71 +/- 3.17 years) and 23 healthy women (50.73 +/- 2.97 years) were
      investigated for body composition, daily physical activity, quality of life,
      salivary cortisol, and DHEA-S. Breast cancer survivors were then aerobically
      trained for 12 weeks. Breast cancer survivors have a worse psychophysical health
      than healthy women. Aerobic training increased salivary DHEA-S, aerobic fitness,
      self-reported health, and nocturnal sleeping time and reduced salivary cortisol
      in breast cancer survivors. Salivary cortisol variation correlated with change of
      sleeping time and self-reported health. Salivary DHEA-S correlated with change of
      self-reported physical pain and general health as well. Breast cancer survivors
      can live in a situation of continuous distress, requiring a multidisciplinary
      approach. Twelve weeks of aerobic training improve the psychophysical health of
      breast cancer survivors.

PMID- 28438276
TI  - Integrating yoga into psychotherapy: The ethics of moving from the mind to the
      mat.
AB  - Given the rise in attention to client preferences in medical treatment and the
      shift in focus toward health promotion, it is not surprising that the use of
      complementary health approaches have increased in the past several years. Yoga is
      among the most prominent complementary health approaches. Recently, both
      qualitative and quantitative work has emerged supporting its use for a variety of
      medical and psychological disorders. However, there is a critical gap in
      knowledge regarding how to most optimally and ethically integrate complementary
      therapies (i.e., yoga) into current psychology practices. Moreover, it remains
      unclear which clients are the best candidates for receiving such complementary
      treatments and which therapists should provide them. The purpose of this paper is
      to provide an overview of the history of yoga, the scientific evidence in support
      of its use for mental health issues, and an ethical framework to guide
      psychologists interested in integrating yoga into psychotherapy.

PMID- 28438277
TI  - The effect of hand reflexology on anxiety in patients undergoing coronary
      angiography: A single-blind randomized controlled trial.
AB  - BACKGROUND: This study aimed to evaluate effects of hand reflexology on anxiety
      level in coronary angiography patients. MATERIALS AND METHODS: This clinical
      trial recruited 80 eligible patients >6 months. The patients were randomly
      assigned to receive routine care plus either hand reflexology or a simple hand
      massage. Data were collected using the Spielberger State-Trait Anxiety Inventory.
      Both groups' anxiety levels were measured before (T0) and 30 min (T1) and 1 h
      after the intervention (T2). FINDINGS: The mean anxiety level in the intervention
      group decreased from 57.54 at baseline to 55.47 after the intervention (P =
      0.0001). The values in the control group were 54.27 and 51.4, respectively. The
      two groups had statistically significant differences in the mean scores of
      anxiety at T0 and T1 (P = 0.003), T1 and T2, and T0 and T2 (P = 0.0001).
      CONCLUSION: Hand reflexology could effectively decrease anxiety in coronary
      angiography patients.

PMID- 28438278
TI  - Complementary and alternative medicine (CAM) among Australian hospital-based
      nurses: knowledge, attitude, personal and professional use, reasons for use, CAM
      referrals, and socio-demographic predictors of CAM users.
AB  - OBJECTIVE: This study was intended to examine CAM among Australian hospital-based
      nurses, identifying their knowledge, attitude, personal and professional use,
      reasons for use, CAM referrals, and socio-demographic predictors of CAM users.
      METHODS AND MATERIALS: Nurses holding a qualification in nursing and working in
      surgical wards were included using a convenience sampling technique. A self
      complete questionnaire was developed to achieve the aims of the study.
      Descriptive and non-parametric statistics were calculated to describe and analyse
      data. RESULTS: Overall, 95.7% and 49.7% of nurses reported personal and
      professional use of CAM, respectively. The most popular CAM/CAM domain personally
      and professionally used by nurses was massage therapy and mind-body therapies.
      The primary reason for personal use of CAM was "[it] fits into my way of
      life/philosophy". Furthermore, massage therapists were the most commonly
      recommended CAM practitioners to patients. Only 15.8% of nurses would always ask
      patients about use of herbal medicines as part of nursing history taking. Over
      one-fifth (22.4%) of nurses rated their attitude as having a very positive, and
      60.3% rated themselves as having very little or no knowledge of CAM. A positive
      correlation was also found between knowledge and attitude about CAM. Positive
      attitude and higher knowledge about CAM were positively correlated to CAM
      referrals. Several socio-demographic factors predicted personal and professional
      use of CAM. CONCLUSION: This study revealed that nurses generally believe not to
      have sufficient knowledge of CAM but are open to use CAM with patients. Nurses'
      positive attitude toward and personal use of CAM could be an indication that they
      are poised for further integration of evidence-based CAM into nursing practice to
      treat whole person.

PMID- 28438279
TI  - Can kinesio tape be used as an ankle training method in the rehabilitation of the
      stroke patients?
AB  - OBJECTIVE: To investigate the effects of the kinesio tape application to the
      tibialis anterior on rehabilitation outcomes of the stroke patients. DESIGN AND
      SETTING: Twenty patients with stroke were allocated into two groups: the first
      group of ten patients was assigned to receive kinesio tape in addition to the
      conventional rehabilitation program while a second group of 10 patients was
      assigned to receive a conventional rehabilitation program only. MAIN OUTCOME
      MEASURES: The clinical variables and health-related quality of life (HRQoL) were
      evaluated at baseline and at the end of the forth week. RESULTS: The present
      study showed that kinesio tape application to the tibialis anterior has
      significant effects on motor recovery of the lower extremity, spasticity,
      ambulation capacity, HRQoL and gait compared to the control group and baseline.
      CONCLUSIONS: The results of this study suggest that kinesio tape can be used as
      an ankle training method.

PMID- 28438280
TI  - Effect of aromatherapy massage on pain in primary dysmenorrhea: A meta-analysis.
AB  - OBJECTIVE: This meta-analysis investigates the effect of aromatherapy massage on
      pain in primary dysmenorrhea. METHODS: Randomized controlled trials were searched
      by keywords in several databases (Pubmed, ISI Web of Sciences, and Google
      Scholar). Six randomized controlled trials that included 362 participants with
      primary dysmenorrhea, comparing abdominal aromatherapy massage (n = 184) with
      massage with placebo oils (n = 178), were analyzed in the meta-analysis. The
      change in the visual analogue scale (VAS) pain score from the first menstruation
      cycle to the second cycle at the first menstruation day was used as the primary
      outcome. RESULTS: Aromatherapy massage with essential oils was superior to
      massage with placebo oils (standardized mean difference = -1.06 [95% CI: -1.55 to
      -0.55]). CONCLUSION: Abdominal aromatherapy massage with essential oils is an
      effective complementary method to relieve pain in primary dysmenorrhea.

PMID- 28438281
TI  - Predictors of positive opinion about Bach Flower Remedies in adults from three
      Latin-American countries: An exploratory study.
AB  - : The current study aimed to determine if positive opinions about BFR interacts
      with spirituality in adults from three Latin-American countries using a CHAID
      algorithm. Participants were 703 adults from Cuba (n = 319), Costa Rica (n = 252)
      and Chile (n = 132). PREDICTORS: demographic data, received information, received
      treatment, spirituality, dispositional optimism and willingness to use a placebo
      intervention were measured and analyzed. A supervised classification which
      included a training phase (n = 423) and a test phase (n = 280) was employed.
      Received information about BFR, spirituality and education were selected as
      significant predictors of the positive opinion about BFR (>90% of correct
      classifications).

PMID- 28438282
TI  - In-vitro susceptibility of methicillin-resistant Stayphylococcus aureus to honey.
AB  - Wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is
      becoming much complicated and costly to treat as antimicrobial resistance is
      quite common. Twenty five MRSA strains isolated from infected wounds and three
      ATCC reference strains were evaluated for their susceptibility to locally
      produced black seed (Nigella sativa), beri (ZiziphusJujuba) and shain honey
      (Plectranthus rugosus wall) by agar incorporation assay. Medically graded manuka
      honey (UMF 21+) was included as control. Locally produced black seed honey
      inhibited all clinical isolates at mean MIC of 5.5% (v/v), whereas manuka honey
      at mean MIC of 4.4% (v/v). The other two locally produced honey; beri and shain
      honey inhibited these isolates at 6.4% and 10.4% (v/v) respectively. The result
      of the study has demonstrated that indigenous black seed honey has comparable
      antibacterial activity to manuka honey and thus offers a good new addition to the
      existing honey resource for the treatment of wound infections.

PMID- 28438283
TI  - Effects of prenatal music stimulation on fetal cardiac state, newborn
      anthropometric measurements and vital signs of pregnant women: A randomized
      controlled trial.
AB  - BACKGROUND: Music has been used for medicinal purposes throughout history due to
      its variety of physiological, psychological and social effects. OBJECTIVE: To
      identify the effects of prenatal music stimulation on the vital signs of pregnant
      women at full term, on the modification of fetal cardiac status during a fetal
      monitoring cardiotocograph, and on anthropometric measurements of newborns taken
      after birth. MATERIAL AND METHOD: A randomized controlled trial was implemented.
      The four hundred and nine pregnant women coming for routine prenatal care were
      randomized in the third trimester to receive either music (n = 204) or no music
      (n = 205) during a fetal monitoring cardiotocograph. All of the pregnant women
      were evaluated by measuring fetal cardiac status (basal fetal heart rate and
      fetal reactivity), vital signs before and after a fetal monitoring
      cardiotocograph (maternal heart rate and systolic and diastolic blood pressure),
      and anthropometric measurements of the newborns were taken after birth (weight,
      height, head circumference and chest circumference). RESULTS: The strip charts
      showed a significantly increased basal fetal heart rate and higher fetal
      reactivity, with accelerations of fetal heart rate in pregnant women with music
      stimulation. After the fetal monitoring cardiotocograph, a statistically
      significant decrease in systolic blood pressure, diastolic blood pressure and
      heart rate in women receiving music stimulation was observed. CONCLUSION: Music
      can be used as a tool which improves the vital signs of pregnant women during the
      third trimester, and can influence the fetus by increasing fetal heart rate and
      fetal reactivity.

PMID- 28438284
TI  - Intradiscal O2O3: Rationale, Injection Technique, Short- and Long-term Outcomes
      for the Treatment of Low Back Pain Due to Disc Herniation.
AB  - The management of low back pain should always start with a conservative approach;
      however, when it fails, intervention is required and at that moment the most
      appropriate choice remains unclear. Before invasive surgery, minimally invasive
      techniques can be adopted. In European trials and in a trans-Canadian clinical
      trial 03 ozone has been used successfully. In total over 50,000 patients have
      been treated safely. Ozone is a gas normally present in the atmosphere with
      potent oxidizing power; it has been used for percutaneous intradiscal injection
      combined with oxygen (O2O3) at very low concentrations for 15 years in Europe.
      The main indication is back pain with or without radicular pain but without motor
      deficits, which is refractory to 4-6 weeks of conservative therapies. Its
      mechanism of action on the disc is mechanical (volume reduction by subtle
      dehydration of the nucleus pulposis) and antinflammatory. The intradiscal ozone
      injection is performed with a thin needle (18-22 gauge) image guided by computed
      tomography or angiofluoroscopy and is usually complimented by periganglionic
      injection of corticosteroids and anesthetics. This combination gives immediate
      pain relief and allows time for the ozone to act. It is a cost-effective
      procedure that presents a very low complication rate (0.1%). The radicular pain
      is resolved before the back pain does, as is seen with microdiscectomy. Peer
      reviewed publications of large randomized trials, case series, and meta analysis
      from large samples of patients have demonstrated the procedure to be safe and
      effective in the short and the long terms, with benefits recognized up to 10
      years after treatment. We aim to review the principles of action of O2O3 and
      report the injection techniques, complications, and short- and long-term
      outcomes.

PMID- 28438285
TI  - Fungal Rhinosinusitis: A Radiological Review With Intraoperative Correlation.
AB  - The interaction between fungi and the sinonasal tract results in a range of
      clinical presentations with a broad spectrum of clinical severity. The most
      commonly accepted classification system divides fungal rhinosinusitis into
      invasive and noninvasive subtypes based on histopathological evidence of tissue
      invasion by fungi. Invasive fungal rhinosinusitis is subdivided into acute
      invasive and chronic invasive categories. The chronic invasive category includes
      a subcategory of chronic granulomatous disease. Noninvasive fungal disease
      includes localized fungal colonization, fungal ball, and allergic fungal
      rhinosinusitis. Noninvasive disease is simply fungal material (or the products of
      the inflammatory reaction of the sinus mucosa) that fills the sinuses but does
      not invade tissue. Bone loss is related to expansion of the sinus(es). Invasive
      disease causes tissue destruction, such that it expands past the bony confines of
      the sinuses. It can rapidly spread, causing acute necrosis. Alternatively, there
      may be slow tissue invasion characterized by symptoms confused with normal
      sinusitis, but destruction of normal nasal and paranasal structures.

PMID- 28438286
TI  - The Paradigm Shift.

PMID- 28438287
TI  - Close surgical margin after conservative parotidectomy in early stage low
      /intermediate-grade parotid carcinoma: Outcome of watch and wait policy.
AB  - AIM: The aim of the study was to assess the watch&wait strategy for management of
      patients with close surgical margin after conservative parotidectomy due to early
      low/intermediate grade parotid carcinoma. PATIENTS AND METHODS: Out of 78
      patients operated on due to primary parotid gland cancer we selected 32 patients
      with a history of parotidectomy, and preservation of 7th nerve, with negative
      (>=1mm), but close (<=5mm) surgical margin and who did not receive supplementary
      radiotherapy due to other indications. Margins ranged from 1 to 3mm (in 27 cases
      it was 1mm, in 3 cases - 2mm and in 2 cases - 3mm), average 1.2mm. The patients
      underwent further clinical-histological analysis. RESULTS: 3 of 32 (9.38%)
      patients experienced a local recurrence 36, 53 and 56months post-surgery. The 5
      year disease-free survival (DFS) was 90.6%. Recurrences were treated surgically,
      followed by radiotherapy, which resulted in an overall survival of 107, 104 and
      104months. One patient died 72months after surgery due to non-oncological causes.
      The 10-year disease-free survival (DFS) was 96.3%. The 3 patients with recurrence
      of cancer had histological diagnosis of epithelial-myoepithelial carcinoma LG,
      with a margin of 2, 1 and 3mm, respectively. There were no other distinctive
      features. CONCLUSION: The watch&wait strategy with intensive follow-up seems
      justified in cases of close margin after excision of I/LG T1/T2 parotid tumors.
      EMC should be considered as a neoplasm associated with higher risk of recurrence.

PMID- 28438288
TI  - Novel quantitative analysis of autofluorescence images for oral cancer screening.
AB  - OBJECTIVES: VELscope(r) was developed to inspect oral mucosa autofluorescence.
      However, its accuracy is heavily dependent on the examining physician's
      experience. This study was aimed toward the development of a novel quantitative
      analysis of autofluorescence images for oral cancer screening. MATERIALS AND
      METHODS: Patients with either oral cancer or precancerous lesions and a control
      group with normal oral mucosa were enrolled in this study. White light images and
      VELscope(r) autofluorescence images of the lesions were taken with a digital
      camera. The lesion in the image was chosen as the region of interest (ROI). The
      average intensity and heterogeneity of the ROI were calculated. A quadratic
      discriminant analysis (QDA) was utilized to compute boundaries based on
      sensitivity and specificity. RESULTS: 47 oral cancer lesions, 54 precancerous
      lesions, and 39 normal oral mucosae controls were analyzed. A boundary of
      specificity of 0.923 and a sensitivity of 0.979 between the oral cancer lesions
      and normal oral mucosae were validated. The oral cancer and precancerous lesions
      could also be differentiated from normal oral mucosae with a specificity of 0.923
      and a sensitivity of 0.970. CONCLUSION: The novel quantitative analysis of the
      intensity and heterogeneity of VELscope(r) autofluorescence images used in this
      study in combination with a QDA classifier can be used to differentiate oral
      cancer and precancerous lesions from normal oral mucosae.

PMID- 28438289
TI  - Impact of fraction size on locally advanced oropharyngeal and nasopharyngeal
      cancers treated with chemoradiation.
AB  - OBJECTIVES: Although chemoradiation regimens have used various fraction sizes, it
      remains unclear how differences in fraction size impact outcomes. MATERIALS AND
      METHODS: Using the National Cancer Database, we identified patients with
      nasopharynx or oropharynx cancers treated between 2004 and 2012 with
      chemoradiation using fraction sizes of 1.8Gy (n=1612), 2Gy (n=8092) or 2.12Gy
      (n=1660). Comparisons between fraction sizes were made in the entire cohort and
      in a propensity matched cohort. RESULTS: Median follow-up was 38.1m. Patients
      receiving 2.12Gy per fraction were more likely to be treated from 2007 to 2012,
      to be treated at an academic center, to have T3-T4 tumors and to have
      oropharyngeal primaries. The 3year overall survival for patients treated with
      1.8Gy, 2Gy and 2.12Gy fraction sizes was 72.9%, 77.8% and 83.3%, respectively
      (P<0.0001). 2.12Gy fraction size was associated with improved survival in
      patients with nasopharynx cancer (P=0.03), base of tongue cancer (P<0.0001) and
      tonsil cancer (P=0.0002). On multivariate analysis, improved survival was
      associated with 2.12Gy fraction sizes compared to 2Gy (HR 1.23, 95% CI 1.09-1.40,
      P=0.001) or 1.8Gy (HR 1.36, 95% CI 1.17-1.58; P<0.0001) fractions sizes.
      CONCLUSION: Chemoradiation regimens using 2.12Gy fraction sizes likely have a
      potential advantage in select nasopharynx and oropharynx cancer patients based on
      age, treatment facility and radiotherapy technique. However, it remains unclear
      if this survival advantage reflected improved disease control due to lack of
      locoregional control data.

PMID- 28438290
TI  - Programmed death ligand 1 (PD-L1) expression and tumor microenvironment:
      Implications for patients with oral precancerous lesions.
AB  - OBJECTIVES: Cancer immunoediting represents a relatively novel concept attempting
      to explain the process of tumor escape from the host immune system response.
      Here, we attempted to elucidate the role of programmed death ligand 1 (PD-L1),
      the tumor microenvironment, and tumor escape mechanisms that allow malignant
      transformation of oral precancerous lesions. MATERIALS AND METHODS: Patients with
      oral precancerous lesions managed at the Nara Medical University Hospital, Japan,
      (n=120) were enrolled in this study. Epithelial dysplasias were graded by
      experienced pathologists, and subepithelial PD-L1-, CD163-, and CD8-positive
      cells were counted in the superficial lamina propria of oral mucosa. Epithelial
      PD-L1 expression was evaluated according to the staining intensity. The
      association of clinicopathological factors with epithelial dysplasia, malignant
      free survival time, and significance of risk factors for malignant transformation
      were determined. RESULTS: Multivariate analysis showed that the subepithelial
      CD163-positive cell count was the only significant risk factor for high-grade
      epithelial dysplasia (P<0.001), while subepithelial CD163- and PD-L1-positive
      cell counts, and epithelial PD-L1 positivity were significantly associated with
      malignant-free survival (P=0.004, 0.04, and <0.001, respectively). Subepithelial
      PD-L1-positive cell count and epithelial PD-L1 positivity were significantly
      associated with malignant transformation (P=0.01 and 0.04, respectively).
      CONCLUSION: Our results indicate that PD-L1-expressing dysplastic epithelial and
      recruited subepithelial cells in oral precancerous legions may evade the host
      immune system, and that the inhibition of PD-1/PD-L1 pathway may potentially
      prevent malignant transformation of oral precancerous legions as well as can
      treat advanced cancers.

PMID- 28438291
TI  - Radiation-induced hypothyroidism after IMRT for nasopharyngeal carcinoma:
      Clinical and dosimetric predictors in a prospective cohort study.
AB  - OBJECTIVES: To investigate the rate and risk factors for developing
      hypothyroidism (HT) in nasopharyngeal carcinoma (NPC) patients treated with
      intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: A total of 135
      consecutive patients treated with IMRT for NPC were prospectively evaluated
      during a median follow up of 34.1months. Serum thyroid function assessments
      before and after IMRT were periodically monitored. To identify risk factors for
      HT occurrence, univariate and multivariate Cox regression analyses were
      performed. RESULTS: Thirty-nine patients (28.9%) developed primary HT. The 2- and
      3-year incidences of primary HT were 29.6% and 43.9%, respectively. The median
      clinical latency for primary HT was 15.1months (3.2-33.8months). No cases of
      central HT were observed. Univariate and multivariate analyses revealed that the
      risk increased with younger age and decreased with higher pretreatment thyroid
      volume. Patients with thyroid mean dose >=45Gy had a 4.9 times increased risk of
      HT than those receiving lower mean dose. Alternatively, the thyroid V45 below 0.5
      and V50 below 0.35 were found to significantly lower the incidence rate of HT.
      CONCLUSION: The incidence of primary HT after IMRT for NPC continued to increase
      with time. The thyroid mean dose constraint was approximately 45Gy. We
      recommended plan optimization objectives to reduce thyroid V45 to 0.5 and V50 to
      0.35.

PMID- 28438293
TI  - Extrathyroidal extension-what does it mean.
AB  - Prognostic factors and risk group analysis are very well known in well
      differentiated thyroid cancer. One of the major prognostic factors is presence of
      extrathyroidal extension and residual gross tumor. It is not uncommon to find the
      final pathology report showing minimal extrathyroidal extension. The debate
      continues as to the implication of this microscopic or minimal extrathyroidal
      extension. The previous staging system had upstaged such tumors. However, several
      reports in the literature suggest no prognostic implication of microscopic or
      minimal extrathyroidal extension.

PMID- 28438292
TI  - Correlation of Crtc1/3-Maml2 fusion status, grade and survival in mucoepidermoid
      carcinoma.
AB  - OBJECTIVE: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of
      the salivary glands. Tumor stage and grade have historically been important
      predictors of survival. An oncogenic CRTC1- or CRTC3-MAML2 gene fusion has been
      identified in a number of MECs. Historically, these gene fusions have been
      associated with lower grade tumors and better survival. However, reported gene
      fusion rates and prognosis varies widely across studies, and have not controlled
      for tumor grade. We sought to identify gene fusion rates and outcomes in our
      cohort of MEC patients. MATERIALS AND METHODS: An IRB-approved retrospective
      cohort of patients with MEC was identified at the University of Michigan.
      Clinical, histologic, and outcome data was collected from medical records. RNA
      was isolated from formalin fixed paraffin-embedded tumor sections, and qRT-PCR
      was performed to identify CRTC1/3-MAML2 gene fusions. Sanger sequencing of qRT
      PCR products was used to confirm gene fusions. RESULTS: Overall, 90 patient MEC
      tumors were collected (58 low-grade, 25 intermediate-grade, and 7 high-grade).
      Gene fusions were identified in 59% (53/90) of tumors. On univariate and
      bivariate analysis, fusion status did not significantly associate with grade or
      survival. CONCLUSION: We have identified a high rate of CRTC1/3-MAML2 gene
      fusions in a large cohort of MEC. We do not identify any correlation between
      fusion status with tumor grade or survival. These findings suggest further
      characterization of MECs is needed before considering the CRTC1/3-MAML2 gene
      fusion as a prognostic biomarker. Additional genetic drivers may account for
      survival and grade in MECs.

PMID- 28438294
TI  - A model using concomitant markers for predicting outcome in human papillomavirus
      positive oropharyngeal cancer.
AB  - OBJECTIVE: Head-neck cancer therapy has become intensified. With radiotherapy
      alone, 3-year disease-free survival (DFS) is 80% for HPV-positive TSCC/BOTSCC and
      better for patients with favorable characteristics, suggesting therapy could be
      tapered for some, decreasing side-effects. Therefore, we built a model to predict
      progression-free survival for patients with HPV-positive TSCC and BOTSCC.
      MATERIAL AND METHODS: TSCC/BOTSCC patients treated curatively between 2000 and
      2011, with HPV16 DNA/E7 mRNA positive tumors examined for CD8+ TILs, HPV16 mRNA
      and HLA class I expression were included. Patients were split randomly 65/35 into
      training and validation sets, and LASSO regression was used to select a model in
      the training set, the performance of which was evaluated in the validation set.
      RESULTS: 258 patients with HPV DNA/E7 mRNA positive tumors could be included, 168
      and 90 patients in the respective sets. No treatment improved prognosis compared
      to radiotherapy alone. CD8+ TIL counts and young age were the strongest
      predictors of survival, followed by T-stage <3 and presence of HPV16 E2 mRNA. The
      model had an area under curve (AUC) of 76%. A model where the presence of three
      of four of these markers defined good prognosis captured 56% of non-relapsing
      patients with a positive predictive value of 98% in the validation set.
      Furthermore, the model identified 35% of our cohort that was overtreated and
      could safely have received de-escalated therapy. CONCLUSION: CD8+ TIL counts,
      age, T-stage and E2 expression could predict progression-free survival,
      identifying patients eligible for randomized trials with milder treatment,
      potentially reducing side effects without worsening prognosis.

PMID- 28438295
TI  - Risk factors for oropharynx cancer in a cohort of HIV-infected veterans.
AB  - OBJECTIVE: To evaluate HIV-related and other clinical risk factors associated
      with oropharynx cancer (OPSCC) in HIV-infected U.S. Veterans. METHODS:
      Retrospective cohort study utilizing Veterans Affairs HIV Clinical Case Registry
      (CCR) data from 1985 to 2010. Outcome was incident OPSCC as indicated by 1
      inpatient or 2 outpatient ICD-9 codes. Cox proportional hazard models were used
      to determine hazard ratios (HR) and 95% confidence intervals (CI) for each risk
      factor on the time to OPSCC diagnosis. RESULTS: A total of 40,996 HIV-infected
      male veterans were included in the cohort with 97 cases of OPSCC. The age
      adjusted incidence rate was 23.2/100,000 [95% CI 17.8-29.2]. Age>50 (aHR=3.8, 95%
      CI 1.9-7.8), recent CD4<200 (aHR=3.8, 95% CI 2.0-7.3), and undetectable HIV viral
      loads 40-79% of the time (aHR=1.8, 95% CI 1.1-3.0) were associated with an
      increased risk of OPSCC. Era of HIV diagnosis, utilization of cART, nadir CD4
      count, race, smoking history, and previous risk of HPV disease, including
      condyloma or invasive squamous cell carcinoma of the anus (SCCA) were not
      associated with increased risk of OPSCC. CONCLUSION: Patients who were older at
      beginning of follow up, had lower CD4 counts around the time of OPSCC diagnosis,
      and moderate HIV viral control during follow-up had an increased risk of OPSCC.
      Other HPV-related diseases such as SCCA and condyloma did not increase the risk
      for OPSCC.

PMID- 28438296
TI  - Discussing HPV with oropharyngeal cancer patients: A cross-sectional survey of
      attitudes in health professionals.
AB  - BACKGROUND: Human papillomavirus (HPV) is now known to cause a significant
      proportion of head and neck cancers (HNC). Qualitative research has shown that
      some health professionals find it difficult to discuss HPV with patients due to
      its sexually transmitted nature, and have concerns about their own knowledge of
      the virus. We used a survey to quantify attitudes towards discussing HPV among
      HNC health professionals. METHODS: We carried out a cross-sectional survey of HNC
      health professionals (n=260) in the UK and Ireland, assessing participants'
      knowledge of HPV, their experiences of and attitudes towards discussing HPV with
      patients, and their willingness to discuss HPV with their patients in the future.
      RESULTS: Overall, health professionals had good knowledge of HPV (mean score:
      9.97 out of 12). Oncologists had significantly greater knowledge than specialist
      nurses, speech and language therapists and 'other' health professionals. Most
      were willing to discuss HPV with patients (mean=4.3 out of 5). Willingness to
      discuss HPV in the future was associated with higher HPV knowledge (r=0.35,
      p<0.001), fewer negative and more positive attitudes towards discussing HPV (r=
      0.23 and r=0.20 respectively, both p<0.001), fewer personal barriers (r=-0.49,
      p<0.001) and greater confidence (r=0.58, p<0.001). CONCLUSION: Knowledge,
      experiences and attitudes to discussing HPV varied across HNC health
      professionals. Addressing gaps in health professionals' HPV knowledge and
      improving their confidence in discussing HPV with patients may increase their
      willingness to have such conversations. This may help minimise the negative
      psychosocial consequences of an HPV diagnosis in this patient group.

PMID- 28438297
TI  - Investigating a case of possible field cancerization in oral squamous cell
      carcinoma by the use of next-generation sequencing.
AB  - OBJECTIVES: Local recurrence and the development of second primary tumors (SPT)
      are important factors that can influence the survival rate of oral squamous cell
      carcinoma (OSCC) patients. We investigate the concept of field cancerization
      which proposes that normal tissue adjacent to the primary tumor harbor pre
      neoplastic alterations that can lead to the development of local recurrence and
      SPTs. MATERIALS AND METHODS: To examine the concept of field cancerization, we
      applied whole-exome and targeted ultra-deep sequencing on 5 freshly frozen
      samples from a stage III OSCC patient from three tumor sites, lymph node
      metastasis and blood. Lastly, we sequenced one formalin-fixed paraffin-embedded
      recurrence biopsy that was collected approximately a year and half later located
      in the same area as before. RESULTS: Sequencing identified 126 somatic mutations.
      We identified 24 mutations in the recurrence biopsy and 14 mutations are shared
      by the primary tumor. CONCLUSION: The low number of shared mutations indicates
      that either these mutations represent a very early clone in the primary tumor's
      evolution, or that these mutations represent a pre-neoplastic field, in which the
      primary tumor and recurrence are derived from. In both instances, the clinical
      recurrence is of a monoclonal origin which suggests either field cancerization by
      migration of mutated cells in the adjacent mucosa, or that the recurrence
      developed out of remaining tumor tissue.

PMID- 28438298
TI  - Intravoxel incoherent motion magnetic resonance imaging in head and neck cancer:
      A systematic review of the diagnostic and prognostic value.
AB  - Intravoxel incoherent motion (IVIM) imaging is increasingly applied in the
      assessment of head and neck cancer (HNC). Our purpose was to determine the
      diagnostic and prognostic performance of IVIM in HNC by performing a critical
      review of the literature. Pubmed and EMBASE were searched until May 2016. Study
      and patients characteristics, imaging protocol and diagnostic or prognostic
      outcomes were extracted by 2 independent reviewers. The studied IVIM parameters
      were diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion
      fraction (f). We included 10 diagnostic studies, 5 prognostic studies and 2
      studies assessing both. Studies were very heterogeneous in terms of applied b
      values, imaging protocols, outcome measurements and reference standards;
      therefore we did not perform a meta-analysis. The most commonly used sequence was
      "spin-echo planar imaging". A median of 10.5 b-values (range, 3-17) were used.
      All but three studies included at least 4 b-values below b=200s/mm2. By combining
      IVIM-parameters squamous cell carcinomas, lymphomas, malignant salivary gland
      tumors, Warthin's tumors and pleomorphic adenomas could be differentiated with a
      sensitivity of 85-87% and specificity of 80-100%. Low pre-treatment D or f and an
      increase in D during treatment were associated with a favorable response to
      treatment. D* appeared to be the parameter with the lowest prognostic value.
      Future research should focus on finding the optimal IVIM protocol, using
      uniformly accepted study methods and larger patient populations.

PMID- 28438299
TI  - Can gene editing and silencing technologies play a role in the treatment of head
      and neck cancer?
AB  - Conventional treatment strategies have done little to improve the prognosis or
      disease-free survival in head and neck cancer (HNC) patients. Recent progress in
      our understanding of molecular aspects of head and neck squamous cell carcinoma
      (HNSCC) has provided insights into the potential use of molecular targeted
      therapies in combination with current treatment strategies. Here we review the
      current understanding of treatment modalities for both HPV-positive and HPV
      negative HNSCCs with the potential to use gene editing and silencing technologies
      therapeutically. The development of sequence-specific RNA interference (RNAi)
      with its strong gene-specific silencing ability, high target specificity, greater
      potency and reduced side effects, has shown it to be a promising therapeutic
      candidate for treating cancers. CRISPR/Cas gene editing is the newest technology
      with the ability to delete, mutate or replace genes of interest and has great
      potential for treating HNSCCs. We also discuss the major challenge in using these
      approaches in HNSCC; that being the choice of target and the ability to deliver
      the payload. Finally, we highlight the potential combination of RNAi or
      CRIPSR/Cas with current treatment strategies and outline the possible path to the
      clinic.

PMID- 28438300
TI  - Malignant transformation of oral lichen planus and oral lichenoid lesions: A meta
      analysis of 20095 patient data.
AB  - OBJECTIVES: For over a century, a heated debate existed over the possibility of
      malignant transformation of oral lichen planus (OLP). We performed this meta
      analysis to evaluate the malignant potential of OLP and oral lichenoid lesions
      (OLL) and investigate the possible risk factors for OLP malignant transformation
      into oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: We searched
      Medline, Scopus, and Web of Knowledge for relevant observational studies. Data on
      OLP malignant transformation were calculated as a pooled proportion (PP), using
      the Der-Simonian Liard method. We performed subgroup analyses by OLP diagnostic
      criteria, site, and clinical type, using Open Meta[Analyst] software. Data on
      possible risk factors for malignant transformation were pooled as odds ratios
      (ORs), using Comprehensive Meta-Analysis software. RESULTS: Pooling data for OLP
      malignant transformation from 57 studies (19,676 patients) resulted in an overall
      PP of 1.1% [95% CI: 0.9%, 1.4%], while pooling data from 14 recent studies that
      used the World Health Organization-2003 diagnostic criteria resulted in an
      overall-PP of 0.9% [95% CI: 0.5%, 1.3%]. The risk of malignant transformation was
      higher (PP=2.5%, 95% CI [1%, 4%]) in OLL patients (419 patients). A significant
      increase of malignant transformation risk was noted among smokers (OR=2, 95% CI
      [1.25, 3.22]), alcoholics (OR=3.52, 95% CI [1.54, 8.03]), and HCV-infected
      patients (OR=5, 95% CI [1.56, 16.07]), compared to patients without these risk
      factors. CONCLUSION: A small subset of OLP patients (1.1%) develop OSCC;
      therefore, regular follow-up for these patients is recommended. A higher
      incidence of malignant transformation was found among smokers, alcoholics, and
      HCV-infected patients; however, these associations should be further
      investigated.

PMID- 28438301
TI  - Typical Presentation of Legionella pneumophila Community-Acquired Pneumonia.

PMID- 28438302
TI  - Undocumented Patients and Rehabilitation Services.

PMID- 28438303
TI  - Relation of the Bilateral Earlobe Crease to Endothelial Dysfunction.
AB  - The presence of an earlobe crease (ELC) may be a simple sign to predict
      atherosclerosis. We evaluated the relation between ELC and vascular function. We
      measured flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation
      (NID) and observed bilateral earlobes in 400 consecutive subjects. At first, the
      subjects were divided into 3 groups: non-ELC group, unilateral ELC group, and
      bilateral ELC group. FMD and NID were significantly lower in the unilateral and
      bilateral ELC groups than those in the non-ELC group. After adjustment of
      cardiovascular risk factors, bilateral ELC, but not unilateral ELC, was
      associated with lower FMD and lower NID. We also investigated whether an increase
      in the number of ELCs worsens endothelial function, whether the difference in ELC
      structure (cross stripes and/or ramification) affects endothelial function, and
      whether endothelial function is impaired in subjects with superficial wrinkles
      depending on age. The number of ELCs, shape of the ELC, and superficial wrinkles
      were not associated with endothelial dysfunction. In conclusion, these findings
      suggest that the presence of bilateral ELCs is associated with vascular
      dysfunction.

PMID- 28438305
TI  - Cardiovascular Response to Recreational Hockey in Middle-Aged Men.
AB  - The present study examined the hemodynamic response to recreational pick-up
      hockey relative to maximal exercise testing in middle-aged men. A total of 23 men
      with a mean age of 53 +/- 7 years were studied. Graded exercise testing on a
      cycle ergometer determined maximal oxygen consumption, blood pressure (BP), and
      heart rate (HR). Ambulatory BP and Holter electrocardiographic monitoring was
      performed during one of their weekly hockey games (mean duration = 45 +/- 7.2
      minutes): for "On-Ice" responses (PLAY; data recorded while standing immediately
      after a shift; 8.0 +/- 1.4 shifts per game) and during seated recovery (BENCH),
      15 minutes after the game. On-Ice HRs and BPs were significantly higher than
      values obtained during maximal cycle exercise, respectively (HR 174 +/- 8.9 vs
      163 +/- 11.0 beats/min) (systolic blood pressure 202 +/- 20 vs 173 +/- 31 mm Hg;
      p <0.05). Both systolic and diastolic blood pressures decreased significantly
      throughout the duration of the game, whereas HR increased from 139 +/- 20 to 155
      +/- 16 beats/min during the game. The myocardial oxygen demand (myocardial time
      tension index) increased significantly during PLAY concurrent with a decrease in
      estimated myocardial oxygen supply (diastolic pressure time index), with the
      endocardial viability ratio during PLAY demonstrating a significant decrease
      during the third quarter of the game (1.25 +/- 0.24) versus the first quarter
      (1.56 +/- 0.30), which remained depressed 15 minutes post-game (p <0.05). In
      conclusion, recreational pick-up hockey in middle-aged men is an extremely
      vigorous interval exercise with increasing relative intensity as the game
      progresses. Hockey elicits peak BPs and HRs that can exceed values observed
      during maximal exercise testing and is characterized by progressive increases in
      myocardial oxygen demand and lowered supply during PLAY and BENCH time. Given the
      progressive and high cardiovascular demands, caution is warranted when estimating
      the cardiovascular demands of hockey from clinical stress testing, particularly
      in those whom coronary reserve may be compromised.

PMID- 28438304
TI  - Thirty-Day Outcomes After Unrestricted Implantation of Bioresorbable Vascular
      Scaffold (from the Prospective RAI Registry).
AB  - The Absorb biovascular scaffold (BVS) is a bioresorbable, everolimus-eluting
      scaffold whose data on real-world patients with complex lesions are limited.
      Short-term follow-up from recent studies point to a higher rate of 30-day
      thrombosis than observed with drug-eluting stents. We aimed to understand the
      short-term safety and efficacy of BVS. Registro Absorb Italiano (RAI,
      ClinicalTrials.gov:NCT02298413) is an Italian, prospective, multicenter registry
      not funded, whose aim is to investigate BVS performance through a 5-year follow
      up of all consecutive patients who have undergone successful implantation of >=1
      BVS in different clinical/lesion subsets. Co-primary end points were target
      lesion revascularization and definite/probable thrombosis. Secondary end point
      was the occurrence of device-oriented cardiac events. The registry involved 23
      centers, with patient enrollment from October 2012 to December 2015. We here
      report the 30-day outcomes of the whole population of the registry. We enrolled
      1,505 consecutive patients, of which 82% were men and 22.4% diabetic. At
      presentation, 59.6% of the patients had an acute coronary syndrome, including 21%
      ST-elevation myocardial infarction. All lesions were pre-dilated and in 96.8% of
      the cases BVS was post-dilated. At 30 days, the co-primary study end point target
      lesion revascularization occurred in 0.6% of patients and definite/probable BVS
      thrombosis in 0.8%. There were 2 cases of cardiac and overall death (0.13%).
      Device-oriented cardiac events occurred in 1% of the patients. In conclusion, our
      data of consecutive patients suggest that current use of BVS in a wide spectrum
      of coronary narrowings and clinical settings is associated with good outcome at
      30 days.

PMID- 28438306
TI  - Relation of Quantity of Subepicardial Adipose Tissue to Infarct Size in Patients
      With ST-Elevation Myocardial Infarction.
AB  - According to the so-called obesity paradox, obesity might present a protective
      role in patients with myocardial infarction. We aimed to assess the influence of
      the epicardial adipose tissue (EAT) volume on cardiac healing and remodeling in
      patients with acute ST-elevation myocardial infarction. We prospectively included
      193 consecutive patients presenting a first STEMI without known coronary artery
      disease. Cardiac magnetic resonance imaging was performed at baseline and after a
      3-month follow-up. EAT volume was computed, and the population was divided into
      quartiles: the highest quartile of EAT defining the high EAT group (h-EAT). h-EAT
      was associated with increased body mass index, higher rate of history of
      hypertension, and smaller infarct size at initial CMR assessment (18.3 +/- 11.9%
      vs 23 +/- 13.7% of total left ventricular [LV] mass, p = 0.041). Moreover,
      microvascular obstruction was less frequent in the h-EAT group (36.2% vs 59.3%, p
      = 0.006). There were no differences in LV ejection fraction (LVEF), LV volumes,
      systolic wall stress, coronary artery burden, and clinical events during the
      index hospitalization between the EAT groups at baseline and at follow-up. Linear
      regression analysis showed h-EAT to be associated with smaller infarct size at
      baseline (beta coefficient = -3.25 [95% CI -5.89 to -0.61], p = 0.016). h-EAT
      also modified positively the effect of infarct size on LV remodeling, as assessed
      by the change in LVEF (p = 0.046). In conclusion, h-EAT was paradoxically related
      to smaller infarct size and acted as an effect modifier in the relation between
      the extent of infarct size and LVEF changes. Patients with higher extent of EAT
      presented better cardiac healing.

PMID- 28438307
TI  - Usefulness of the Combination of In-Hospital Poor Diuretic Response and Systemic
      Congestion to Predict Future Cardiac Events in Patients With Acute Decompensated
      Heart Failure.
AB  - We aimed to (1) investigate the relation between diuretic response (DR) with or
      without systemic congestion and prognosis and (2) explore the potential
      predictors of poor DR for risk stratification in patients with acute
      decompensated heart failure (ADHF). We enrolled 186 consecutive patients
      hospitalized for ADHF. The DR was defined as (body weight at discharge - body
      weight at admission)/40 mg furosemide or equivalent loop diuretic dose. Systemic
      congestion on admission was simply evaluated by the presence of leg edema or
      jugular venous distention. All patients were divided into 4 groups based on the
      median of DR (-0.50 kg/40 mg) and the status of systemic congestion; GR/C (good
      DR with systemic congestion, n = 66), GR/N (good DR without systemic congestion,
      n = 27), PR/C (poor DR with systemic congestion, n = 48); and PR/N (poor DR
      without systemic congestion, n = 45). The composite outcome was defined as
      cardiac death and rehospitalization for worsening heart failure. In survival
      analysis, the cardiac event-free rate in PR/C was significantly lower than that
      in any other groups (log-rank, p <0.001), and PR/C was an independent predictor
      of cardiac events (hazard ratio 2.17, p = 0.016). In conclusion, the combination
      of in-hospital poor DR, characterized by previous ischemic heart disease, and
      prehospital dose of daily loop diuretics, and systemic congestion provides a risk
      stratification for future cardiac events in patients with ADHF.

PMID- 28438308
TI  - Cardiovascular Outcomes With Surgical Left Atrial Appendage Exclusion in Patients
      With Atrial Fibrillation Who Underwent Valvular Heart Surgery (from the National
      Inpatient Sample Database).
AB  - Left atrial appendage (LAA) exclusion is a commonly performed procedure to reduce
      the embolic events in patients with atrial fibrillation (AF) who underwent
      cardiac surgeries. Our study aimed to evaluate the in-hospital outcomes of LAA
      exclusion in patients with AF who underwent valvular heart surgeries. We queried
      the Nationwide Inpatient Sample Database from 1998 to 2013 for patients with the
      International Classification of Diseases, Ninth Edition, Clinical Modification,
      diagnosis codes for AF and underwent any valvular heart surgery. We then
      performed a case-control matching based on the CHA2DS2VASc score for those who
      underwent LAA exclusion versus those who did not. Primary outcome was the
      incidence of in-hospital cerebrovascular events, whereas the secondary outcomes
      included all-cause mortality, length of hospital stay, and bleeding. Our analysis
      included 1,304 patients. Patients who underwent LAA exclusion had significantly
      less incidence of cerebrovascular events (2.5% vs 4.6%, p = 0.04), in-hospital
      death (1.5% vs 4.9%, p = 0.001), and shorter hospital stay (10.5 vs 12.9 days, p
      <0.01). The LAA exclusion cohort had more incidence of pericardial effusion (1.3%
      vs 0.5%, p = 0.04) but no difference in bleeding events (p = 0.55). In
      conclusion, in patients with AF who underwent valvular surgeries, LAA exclusion
      may be associated with lower in-hospital cerebrovascular events and mortality and
      shorter hospital stay.

PMID- 28438310
TI  - Reply.

PMID- 28438309
TI  - Association of Albuminuria With Cardiac Dysfunction in US Hispanics/Latinos.
AB  - Higher urine albumin-to-creatinine ratio (UACR) has been associated with cardiac
      dysfunction in the general population. We assessed the association of UACR with
      cardiac structure and function in the Echocardiographic Study of Latinos (Echo
      SOL), an ancillary study of the Hispanic Community Health Study/Study of Latinos
      across 4 US sites. Echo-SOL participants underwent standard 2-dimensional
      echocardiography, including speckle-tracking strain analysis. UACR was
      categorized as normal and high-normal (based on the midpoint of values below
      microalbuminuria), microalbuminuria (>=17 mg/g for men; >=25 mg/g for women), and
      macroalbuminuria (>=250 mg/g; >=355 mg/g). Simultaneous assessments were made of
      left ventricular (LV) mass index and hypertrophy and measures of LV systolic and
      diastolic dysfunction. We assessed the association of UACR with subclinical
      cardiac measures, adjusting for sociodemographic and cardiometabolic factors.
      Among 1,815 participants (median age 54, women 65%), 42% had normal UACR, 43%
      high-normal UACR, 13% microalbuminuria, and 2% macroalbuminuria. Prevalence of LV
      hypertrophy was 13%, LV systolic dysfunction (ejection fraction <50%) 3%, and
      diastolic dysfunction 53%. After covariate adjustment, both micro- and
      macroalbuminuria were significantly associated with a twofold increase in LV
      hypertrophy. Microalbuminuria but not macroalbuminuria was associated with worse
      global longitudinal strain. Elevated UACR, even at high-normal levels, was
      significantly associated with greater diastolic dysfunction. In conclusion,
      elevated UACR was associated with LV hypertrophy and diastolic dysfunction in the
      largest known population sample of US Hispanic/Latinos. Screening and detection
      of even high-normal UACR could be of value to guide cardiovascular disease
      prevention efforts among Hispanic/Latino Americans.

PMID- 28438311
TI  - Aqueous Humor Cytokines in Patients With Acute Nonarteritic Anterior Ischemic
      Optic Neuropathy.

PMID- 28438312
TI  - Comment on "Combination of cupric ion with hydroxylamine and hydrogen peroxide
      for the control of bacterial biofilms on RO membranes by Hye-Jin Lee, Hyung-Eun
      Kim, Changha Lee [Water Research 110, 2017, 83-90]".
AB  - The methodology employed by Lee et al. to terminate their bactericidal assays was
      found to be flawed via our demonstrations. Briefly, EDTA or sulfite combining
      with cupric ion did not fully terminate, and instead even boosted the P.
      aeruginosa death. We therefore suggested them to seek for other means of reaction
      termination, such as the combination of buffering agent PBS and Cu(II)-complexing
      agent EDTA.

PMID- 28438313
TI  - Analysis of the metal layer thickness influence on the dispersion characteristics
      of acoustic waves propagating in the layered piezoelectric structure
      "Me/AlN/Me/diamond".
AB  - The paper presents the results of computer simulation of the acoustic waves
      propagation in piezoelectric layered structures based on diamond substrate under
      the influence of various metal film deposition. It has been observed that the
      maximum phase velocity change Deltav/v is achieved with an "Au/(001) AlN/Au/(100)
      diamond" PLS configuration. However, if the acoustic impedance of the metal layer
      is greater than the acoustic impedance of the substrate, an elastic wave
      reflection can be observed, reducing the Deltav/v quantities. Obtained results
      may be useful in the development of resonant and sensor acousto-electronic
      devices based on the Rayleigh and Love waves.

PMID- 28438314
TI  - Progression of experimental autoimmune encephalomyelitis is associated with up
      regulation of major sodium transporters in the mouse kidney cortex under a normal
      salt diet.
AB  - Recent demonstrations of exacerbation of experimental autoimmune
      encephalomyelitis (EAE) by high salt diets prompted us to study whether EAE
      stimulated Na absorption by the renal cortex, a primary regulatory site for Na
      balance, even under a normal NaCl diet. We found that as EAE progressed from mild
      to severe symptoms, there were parallel increases in the protein abundance of
      NHE3 and alphaENaC and the Na,K-ATPase activity with an affiliated elevation of
      its beta1-subunit protein. These effects are associated with increases in the
      protein levels of the well-known regulators SGK1 and scaffold NHERF2, and
      phosphorylation of ERK1/2. These effects of EAE could not be explained by
      reduction in water or food intake. We conclude that EAE progression is associated
      with up-regulation of major Na transporters, which is most likely driven by
      increased expression of SGK1 and NHERF2 and activation of ERK1/2. These data
      suggest that EAE progression increases Na absorption by the renal cortex.

PMID- 28438315
TI  - TGF-beta1 improving abnormal pregnancy outcomes induced by Toxoplasma gondii
      infection: Regulating NKG2D/DAP10 and killer subset of decidual NK cells.
AB  - Our current aim was to investigate whether injection of TGF-beta1 played an
      important role in improving abnormal pregnancy outcomes with T. gondii infection
      and how the TGF-beta1 regulated. Results showed that TGF-beta1 exhibited improved
      pregnancy outcomes induced by T. gondii infection. dNK cytotoxicity was increased
      with T. gondii infection while decreased with TGF-beta1 treatment. dNK
      cytotoxicity related NKG2D/DAP10 expression, perforin, granzyme, IFN-gamma and
      killer subsets were all increased with T. gondii infection while decreased after
      TGF-beta1 treatment. In addition, anti-TGF-beta1 antibodies could aggregate the
      cytotoxicity of dNK cells and the levels of molecules above. These results
      indicated that TGF-beta1 treatment could improve the abnormal pregnancy outcomes
      with T. gondii infection by decreasing the cytotoxicity of dNK cells mediated by
      NKG2D/DAP10 pathway and killer subset. These results suggested that TGF-beta1
      might be a potential immunoprotective method for the treatment of abnormal
      pregnancy outcomes following T. gondii infection.

PMID- 28438316
TI  - Multiple modes of capillary electrophoresis applied in peptide nucleic acid
      related study.
AB  - Peptide Nucleic Acid (PNA) is a nucleic acid analogue, whose neutrally charged
      and hydrophobic backbone makes it more stable in vivo, so it might act as a
      potentially better protein probe as compared to aptamer. Currently the
      investigation of PNA and protein interaction is scarce. In this research,
      multiple modes of capillary electrophoresis were established and applied for PNA
      characterization and its interaction with ssDNA and protein. A 15-mer PNA having
      the same nucleobase sequence as 15-mer anti-thrombin DNA aptamer was chosen as
      PNA model for this study, its pI (7.71) was estimated by capillary isoelectric
      focusing (cIEF). Due to its neutral charge and strong hydrophobicity, three
      micellar electrokinetic chromatography (MEKC) modes containing (a) SDS, (b)
      Triton X-100 and (c) CTAB were compared for PNA related analysis. CTAB was not
      applicable for PNA analysis, while in 4mM SDS or 2mM Triton X-100, PNA and PNA
      ssDNA complex can be identified directly. The significant peak of PNA-ssDNA
      complex helped in validating the two MEKC modes for PNA and target interaction
      study. Furthermore, the effect of SDS and Triton X-100 concentrations in the two
      MEKC modes on the protein target thrombin analysis was investigated by capillary
      zone electrophoresis (CZE). 4mM SDS caused thrombin denaturation. So in 2mM
      Triton X-100, interactions of PNA with thrombin, PNA with RNase A and a non
      aptameric PNA (n-PNA) with thrombin were compared. PNA with thrombin exhibited
      strongest binding. In summary, cIEF mode for PNA pI determination, MECK mode for
      direct PNA, PNA-ssDNA and PNA-protein complex identification and CZE mode for the
      effect of surfactant in MEKC modes on protein target thrombin analysis were
      applied. Above results showed that multiple modes of CE provide rapid and very
      low-sample cost methods for PNA related studies.

PMID- 28438317
TI  - A chromatographic approach to distinguish Gram-positive from Gram-negative
      bacteria using exogenous volatile organic compound metabolites.
AB  - This paper utilized L-alanine aminopeptidase activity as a useful approach to
      distinguish between Gram-negative and Gram-positive bacteria. This was done using
      two enzyme substrates, specifically 2-amino-N-phenylpropanamide and 2-amino-N-(4
      methylphenyl)propanamide which liberated the volatile compounds aniline and p
      toluidine, respectively. Two complementary analytical techniques have been used
      to identify and quantify the VOCs, specifically static headspace multicapillary
      column gas chromatography ion mobility spectrometry (SHS-MCC-GC-IMS) and
      headspace solid phase microextraction gas chromatography mass spectrometry (HS
      SPME-GC-MS). Superior limits of detection were obtained using HS-SPME-GC-MS,
      typically by a factor of x6 such that the LOD for aniline was 0.02MUg/mL and
      0.01MUg/mL for p-toluidine. In addition, it was also possible to determine indole
      interference-free by HS-SPME-GC-MS at an LOD of 0.01MUg/mL. The approach was
      applied to a range of selected bacteria: 15 Gram-negative and 7 Gram-positive
      bacteria. Use of pattern recognition, in the form of Principal Component
      Analysis, confirmed that it is possible to differentiate between Gram-positive
      and Gram-negative bacteria using the enzyme generated VOCs, aniline and p
      toluidine. The exception was Stenotrophomonas maltophilia which showed negligible
      VOC concentrations for both aniline and p-toluidine, irrespective of the
      analytical techniques used and hence was not characteristic of the other Gram
      negative bacteria investigated. The developed methodology has the potential to be
      applied for clinical and food applications.

PMID- 28438318
TI  - The affinities of Homo floresiensis based on phylogenetic analyses of cranial,
      dental, and postcranial characters.
AB  - Although the diminutive Homo floresiensis has been known for a decade, its
      phylogenetic status remains highly contentious. A broad range of potential
      explanations for the evolution of this species has been explored. One view is
      that H. floresiensis is derived from Asian Homo erectus that arrived on Flores
      and subsequently evolved a smaller body size, perhaps to survive the constrained
      resources they faced in a new island environment. Fossil remains of H. erectus,
      well known from Java, have not yet been discovered on Flores. The second
      hypothesis is that H. floresiensis is directly descended from an early Homo
      lineage with roots in Africa, such as Homo habilis; the third is that it is Homo
      sapiens with pathology. We use parsimony and Bayesian phylogenetic methods to
      test these hypotheses. Our phylogenetic data build upon those characters
      previously presented in support of these hypotheses by broadening the range of
      traits to include the crania, mandibles, dentition, and postcrania of Homo and
      Australopithecus. The new data and analyses support the hypothesis that H.
      floresiensis is an early Homo lineage: H. floresiensis is sister either to H.
      habilis alone or to a clade consisting of at least H. habilis, H. erectus, Homo
      ergaster, and H. sapiens. A close phylogenetic relationship between H.
      floresiensis and H. erectus or H. sapiens can be rejected; furthermore, most of
      the traits separating H. floresiensis from H. sapiens are not readily
      attributable to pathology (e.g., Down syndrome). The results suggest H.
      floresiensis is a long-surviving relict of an early (>1.75 Ma) hominin lineage
      and a hitherto unknown migration out of Africa, and not a recent derivative of
      either H. erectus or H. sapiens.

PMID- 28438319
TI  - Do we really need another individual coronary plaque characterization
      measurement?

PMID- 28438320
TI  - Critical care nurses' perceptions of the outcomes of working overtime in Canada.
AB  - BACKGROUND: Nursing overtime is being integrated into the normal landscape of
      practice to ensure optimal staffing levels and addresses variations in patient
      volume and acuity. This is particularly true in critical care where fluctuations
      in either are difficult to predict. PURPOSE: The goal of this study was to
      explore critical care nurses' perceptions of the outcomes of working overtime.
      METHODS: Sally Thorne's interpretive description guided the collection and
      analysis of data. Participants were recruited from 11 different critical care
      units within three large teaching hospitals in Southern Ontario, Canada. A total
      of 28 full- and part-time registered nurses who had worked in an intensive care
      unit for at least one year took part in this study. Data were collected through
      semistructured, audio-recorded, individual interviews that took place in rooms
      adjacent to participants' critical care units. Template analysis facilitated the
      determination and abstraction of themes using NVivo for Mac 10.1.1. FINDINGS:
      Major themes highlighting the perceived outcomes of overtime included (a)
      physical effects, (b) impact on patient-centered care, (c) balancing family and
      work, (d) financial gain, and ? safety is jeopardized. CONCLUSIONS: Nursing
      managers and institutions need to be accountable for staffing practices they
      institute, and nurses themselves may require further education regarding healthy
      work-life balance. There are both negative and positive consequences of nursing
      overtime for nurses and patients, but nurses at large valued the option to work
      it.

PMID- 28438321
TI  - Commentary: Building a mentoring network.

PMID- 28438322
TI  - Water-fat Dixon sequences in the evaluation of breast implants: proposal of a
      time effective rapid approach in the clinical practice.
AB  - AIM: To evaluate the diagnostic accuracy achieved from a fat-water Dixon sequence
      alone compared to a combination of a silicone-specific magnetic resonance imaging
      (MRI) sequence and a water-specific MRI sequence in the assessment of breast
      implants. MATERIALS AND METHODS: In this institutional review board (IRB)
      approved study the integrity of breast implants was assessed retrospectively in
      27 patients undergoing breast MRI at 3 T. A qualitative evaluation of (set 1) a
      silicon-selective water-saturated short tau inversion recovery (STIR) sequence in
      combination with a water-only Dixon dataset (total acquisition time 7 minutes 17
      seconds), and of (set 2) fat-only and water-only Dixon datasets (4 minutes 8
      seconds) was performed by two readers independently evaluating the following
      features: margin definition of the implant, water suppression homogeneity, image
      quality, presence of artefacts and their effects on the imaging interpretation,
      and diagnostic confidence. Diagnostic accuracy in implant rupture detection was
      determined and either surgical confirmation or diagnosis from the radiological
      report was used as a standard of reference. RESULTS: In both sequences, margin
      definition of the implant wall, water suppression homogeneity, and overall image
      quality were rated good-excellent in most of cases. Water suppression homogeneity
      was moderate-poor in a greater number of cases in set 1. Movement artefacts were
      more frequent in set 1 whereas five cases (18.5%) exhibited swap artefacts
      between silicone and water in set 2. Diagnostic confidence was rated high-very
      high with both sequences in most of cases. Diagnostic accuracy was 100% for both
      readers using set 1 and 96.2% and 100% using set 2. CONCLUSION: A single Dixon
      sequence allows an accurate diagnostic evaluation of breast implants and
      concomitant shortening of the overall acquisition time.

PMID- 28438323
TI  - Virtual Special Issue - Chronic liver disease.

PMID- 28438324
TI  - Rikki-Tikki-Tavi for aortic regurgitation.

PMID- 28438325
TI  - Atherosclerotic arch and anemia: A dangerous combination.

PMID- 28438326
TI  - Transapical transcatheter aortic valve implantation using the J-Valve system: A 1
      year follow-up study.
AB  - OBJECTIVE: Transcatheter aortic valve implantation has become a routine procedure
      to treat screened inoperable or high-risk patients. In this study, we present the
      first outcome of echocardiographic midterm using a new second-generation
      transcatheter aortic valve implantation system, the J-Valve system (Jie Cheng
      Medical Technologies, Suzhou, China), in patients with aortic stenosis or aortic
      regurgitation. METHODS: From July 2014 to June 2015, 21 patients with isolated
      aortic valve disease at high risk for open surgery received transapical
      transcatheter aortic valve implantation using the J-Valve system. The primary end
      point was a combined efficacy end point after 1 year, which included all-cause
      mortality after more than 30 days and failure of current therapy for aortic
      stenosis or aortic regurgitation requiring hospitalization for symptoms of valve
      related cardiac decompensation or prosthetic heart valve dysfunction. Secondary
      end points were cardiovascular mortality, major stroke, and life-threatening,
      disabling, or major bleeding after 6 and 12 months. RESULTS: The mean age of the
      study cohort was 75.52 +/- 5.22 years, the European System for Cardiac Operative
      Risk Evaluation II score was 11.33% +/- 1.28%, and the mean logistic European
      System for Cardiac Operative Risk Evaluation I score was 31.13% +/- 9.68%.
      Transcatheter aortic valve implantation with the J-Valve system was successfully
      performed in 19 of the 21 patients (90.5%). For patients with aortic stenosis, 12
      month follow-up echocardiography demonstrated an increase in mean effective valve
      area from 0.62 +/- 0.17 cm2 to 1.52 +/- 0.35 cm2 and a decrease in transvalvular
      mean gradient from 61 +/- 15 mm Hg to 18 +/- 9 mm Hg. All surviving patients (n =
      18) reported improvements in at least 1 of the New York Heart Association
      classes. The combined ratio of successful implantation and absence of adverse
      events in our cohort (n = 21) was 76.19%. CONCLUSIONS: The J-Valve system
      exhibits a convincing midterm performance and is a safe and feasible procedure
      with low perioperative and postoperative complications.

PMID- 28438327
TI  - Doctor, I say yes to a good old coronary bypass operation and no to your new
      blood pump!

PMID- 28438328
TI  - Left ventricular assist device explant versus decommission for myocardial
      recovery.

PMID- 28438329
TI  - Extracorporeal membrane oxygenation therapy for postcardiotomy cardiogenic shock.

PMID- 28438330
TI  - Demonic possession by Jean Lhermitte.
AB  - The name of the French neurologist and psychiatrist Jean Lhermitte (1877-1959) is
      most often associated with the sign he described back in 1927 in three patients
      with multiple sclerosis. We are reporting unpublished handwritten notes by Jean
      Lhermitte about 'demonic possession', which date from the 1950s. Drawing from his
      experiences in neuropsychiatry, Lhermitte gathered notable case reviews as well
      as individual case histories. For him, cases of demonic possession are of a
      psychiatric nature with social background exerting a strong influence. Like Freud
      did earlier, Lhermitte believes that the majority of those possessed people have
      been subjected to sexual trauma with scruples, often linked to religion. Demonic
      possession cases were not so rare in the 1950s but their number has nowadays
      declined substantially with the development of modern psychiatry.

PMID- 28438331
TI  - [The intestinal microbiota: A new player in depression?]
AB  - : Depression is the leading cause of disability in the world according to the
      World Health Organization. The effectiveness of the available antidepressant
      therapies is limited. Data from the literature suggest that some subtypes of
      depression may be associated with chronic low grade inflammation. The uncovering
      of the role of intestinal microbiota in the development of the immune system and
      its bidirectional communication with the brain have led to growing interest on
      reciprocal interactions between inflammation, microbiota and depression. Our
      purpose is to review the state of knowledge on these interactions. METHODS: We
      carried out a literature search on Pubmed, Go pubmed, psyC info, Elsevier, Embase
      until August 13, 2016 using the keywords "depression", "microbiota" and
      "inflammation". RESULTS: Dysbiosis reported in patients suffering from depression
      seems to contribute to low grade systemic inflammation which in turn feeds back
      depression. The hypothetical mechanisms behind these interactions are multiple:
      leaky gut, hyperreactivity of the corticotropic axis, disturbed
      neurotransmission. Abnormal microbial exposure during childhood and perinatal
      stress are reported to influence both the maturation of the immune system and the
      microbiota hence contributing to the ethiopathogeny of depression. There is no
      evidence in the literature to support a role for diet. CONCLUSION: The evidence
      supporting a causal relationship between dysbiosis and depression through low
      grade inflammation is limited and precludes us from drawing firm conclusions.
      Further studies are needed to improve our knowledge.

PMID- 28438332
TI  - Adaptive fuzzy wavelet network control of second order multi-agent systems with
      unknown nonlinear dynamics.
AB  - In this paper, consensus problem is considered for second order multi-agent
      systems with unknown nonlinear dynamics under undirected graphs. A novel
      distributed control strategy is suggested for leaderless systems based on
      adaptive fuzzy wavelet networks. Adaptive fuzzy wavelet networks are employed to
      compensate for the effect of unknown nonlinear dynamics. Moreover, the proposed
      method is developed for leader following systems and leader following systems
      with state time delays. Lyapunov functions are applied to prove uniformly
      ultimately bounded stability of closed loop systems and to obtain adaptive laws.
      Three simulation examples are presented to illustrate the effectiveness of the
      proposed control algorithms.

PMID- 28438333
TI  - Can postoperative process of care utilization or complication rates explain the
      volume-cost relationship for cancer surgery?
AB  - BACKGROUND: Past studies identify an association between provider volume and
      outcomes, but less is known about the volume-cost relationship for cancer
      surgery. We analyze the volume-cost relationship for 6 cancer operations and
      explore whether it is influenced by the occurrence of complications and/or
      utilization of processes of care. METHODS: Medicare hospital and inpatient claims
      for the years 2005 through 2009 were analyzed for 6 cancer resections: colectomy,
      rectal resection, pulmonary lobectomy, pneumonectomy, esophagectomy, and
      pancreatic resection. Regressions were first estimated to quantify the
      association of provider volume with costs, excluding measures of complications
      and processes of care as explanatory variables. Next, these variables were added
      to the regressions to test whether they weakened any previously observed volume
      cost relationship. RESULTS: Higher hospital volume is associated with lower
      patient costs for esophagectomy but not for other operations. Higher surgeon
      volume reduces costs for most procedures, but this result weakens when processes
      of care are added to the regressions. Processes of care that are frequently
      implemented in response to adverse events are associated with 14% to 34% higher
      costs. Utilization of these processes is more prevalent among low-volume versus
      high-volume surgeons. CONCLUSION: Processes of care implemented when
      complications occur explain much of the surgeon volume-cost relationship. Given
      that surgeon volume is readily observed, better outcomes and lower costs may be
      achieved by referring patients to high-volume surgeons. Increasing patient access
      to surgeons with lower rates of complications may be the most effective strategy
      for avoiding costly processes of care, controlling expenditure growth.

PMID- 28438334
TI  - Understanding patterns of injury in Kenya: Analysis of a trauma registry data
      from a National Referral Hospital.
AB  - BACKGROUND: Injuries contribute to a substantial proportion of the burden of
      disease in Kenya. Trauma registries can be a very useful source of data to
      understand patterns of injuries and serve to provide information about potential
      improvements in the care of injured patients. In Kenya, health facility-based
      injury data has been largely administrative. Our aim was to develop and implement
      a prospective trauma registry at the largest trauma hospital in Kenya, the
      Kenyatta National Hospital, and to understand the nature of injuries presenting
      to the hospital, their treatment and care, and their outcomes. METHODS: An
      electronic, tablet-based instrument was developed and implemented between January
      2014 and June 2015. Data were collected at the emergency department, and patients
      were followed through disposition from the emergency department or in-patient
      wards if admitted. Variables included demographics, type of prehospital care
      received, details of the injury, and initial assessment and disposition from the
      emergency department or in-patient wards. Bivariate and multiple logistic
      regressions were used to assess potential risk factors associated with outcomes.
      RESULTS: A total of 8,701 injury patients were included in the registry during
      the study period. The mean age of the injured patients was 28 years (standard
      deviation, 26 years). The majority of these patients were males (81.7%). The
      leading mechanisms of injuries were road traffic injury (41.7%), assault (25.3%),
      and falls (18.9%). Only 7.4% of patients received prehospital care; 49.6% of
      injured patients arrived within 1 hour after their injury. Hospital mortality was
      4.4% and close to 1% of patients died in the emergency department. The
      independent predictors of in-hospital death were older age (>=60 years), injury
      mechanism (burns and road traffic injuries), and admission type (transfer) after
      controlling for injury severity. CONCLUSION: The establishment of hospital-based
      trauma registries can be an important tool for injury surveillance. This
      information will facilitate identifying priority areas for trauma care and
      quality improvement, as well as guiding the development of injury prevention and
      control programs.

PMID- 28438335
TI  - An unusual case of mediastinal paraganglioma and pituitary adenoma.

PMID- 28438337
TI  - Carboxylesterase activities in chondrichthyans of the western Mediterranean Sea.

PMID- 28438338
TI  - Effects of polychlorinated biphenyls on metamorphosis of a marine fish Japanese
      flounder (Paralichthys olivaceus) in relation to thyroid disruption.
AB  - This study examined the influence of environmental concentrations of Aroclor 1254
      (10, 100, and 1000ng/L) on metamorphosis of Paralichthys olivaceus, and analyzed
      the mechanisms in relation to thyroid disruption. Results showed that 100 and
      1000ng/L Aroclor 1254 delayed metamorphosis and that 1000ng/L Aroclor 1254 caused
      abnormal morphology. Thyroxine and triiodothyronine levels in the control group
      were significantly elevated at metamorphic climax, but treatment with 100 and
      1000ng/L delayed the increase in thyroid hormones (THs) and retarded metamorphic
      processes. In larvae exposed to 1000ng/L Aroclor 1254, TH levels at metamorphic
      climax were significantly lower than those of the control group at the same
      metamorphic stage. We suggest that the effects of Aroclor 1254 on larval
      metamorphosis can be explained by disruption of thyroid homeostasis. These
      findings provide a new perspective and biological model for thyroid-disrupting
      chemicals (TDCs) screening and investigating interference of thyroid function by
      TDCs.

PMID- 28438336
TI  - Distinct cis-acting regions control six6 expression during eye field and optic
      cup stages of eye formation.
AB  - The eye field transcription factor, Six6, is essential for both the early
      (specification and proliferative growth) phase of eye formation, as well as for
      normal retinal progenitor cell differentiation. While genomic regions driving
      six6 optic cup expression have been described, the sequences controlling eye
      field and optic vesicle expression are unknown. Two evolutionary conserved
      regions 5' and a third 3' to the six6 coding region were identified, and together
      they faithfully replicate the endogenous X. laevis six6 expression pattern.
      Transgenic lines were generated and used to determine the onset and expression
      patterns controlled by the regulatory regions. The conserved 3' region was
      necessary and sufficient for eye field and optic vesicle expression. In contrast,
      the two conserved enhancer regions located 5' of the coding sequence were
      required together for normal optic cup and mature retinal expression. Gain-of
      function experiments indicate endogenous six6 and GFP expression in F1 transgenic
      embryos are similarly regulated in response to candidate trans-acting factors.
      Importantly, CRISPR/CAS9-mediated deletion of the 3' eye field/optic vesicle
      enhancer in X. laevis, resulted in a reduction in optic vesicle size. These
      results identify the cis-acting regions, demonstrate the modular nature of the
      elements controlling early versus late retinal expression, and identify potential
      regulators of six6 expression during the early stages of eye formation.

PMID- 28438339
TI  - Mercury, arsenic, cadmium and lead in two commercial shark species (Sphyrna
      lewini and Caraharinus porosus) in Trinidad and Tobago.
AB  - Sharks are long-lived apex predators which can accumulate toxic metals such as
      mercury and arsenic. Samples of Sphyrna lewini and Carcharinus porosus were
      collected from two commercial fish landing sites in Trinidad. Heavy metal
      concentrations were determined in the muscle, dorsal fin, vertebrae and liver
      using atomic absorption spectrometric. The provisional tolerable weekly intake
      (PTWI) and target hazard quotient (THQ) were determined to assess the potential
      health risks to consumers. Mercury levels ranged between 74-1899MUg/kg in S.
      lewini and 67-3268MUg/kg in C. porosus. Arsenic levels ranged between 144
      2309MUg/kg in S. lewini and 762-6155MUg/kg in C. porosus. Cadmium levels
      generally ranged between 0.27-27.29mg/kg in S. lewini and 0.6-29.89mg/kg in C.
      porosus. Lead levels generally ranged between 0.14 and 208.81mg/kg in S. lewini
      while C. porosus levels ranged between 0.30 and 459.94mg/kg. The PTWI and THQ
      values suggest that consumption of these shark species can therefore be a major
      source of exposure to lead, cadmium, arsenic and mercury in humans and is likely
      to have potential health risk over long term exposure.

PMID- 28438341
TI  - In Reply to 'Why ELAIN and AKIKI Should Not Be Compared: Resolving Discordant
      Studies'.

PMID- 28438342
TI  - Why ELAIN and AKIKI Should Not Be Compared: Resolving Discordant Studies.

PMID- 28438340
TI  - Applications of pHLIP Technology for Cancer Imaging and Therapy.
AB  - Acidity is a biomarker of cancer that is not subject to the blunting clonal
      selection effects that reduce the efficacy of other biomarker technologies, such
      as antibody targeting. The pH (low) insertion peptides (pHLIP(r)s) provide new
      opportunities for targeting acidic tissues. Through the physical mechanism of
      membrane-associated folding, pHLIPs are triggered by the acidic microenvironment
      to insert and span the membranes of tumor cells. The pHLIP platform can be
      applied to imaging acidic tissues, delivering cell-permeable and impermeable
      molecules to the cytoplasm, and promoting the cellular uptake of nanoparticles.
      Since acidosis is a hallmark of tumor development, progression, and
      aggressiveness, the pHLIP technology may prove useful in targeting cancer cells
      and metastases for tumor diagnosis, imaging, and therapy.

PMID- 28438344
TI  - Negative Endobronchial Ultrasound in Lung Cancer Staging.

PMID- 28438343
TI  - Developmental and Transmittable Origins of Obesity-Associated Health Disorders.
AB  - The current global obesity pandemic is clearly linked to both the increasing
      prevalence of, and preference for, foods high in calories, specifically fat and
      sucrose, and declining levels of daily physical activity. A less commonly
      discussed possible explanation is that risk of obesity begins in utero as a
      result of developmental plasticity during early life. This idea fits into the
      broader Developmental Origins of Health and Diseases (DOHAD) hypothesis, which
      holds that stressful in utero exposure manifests as disease in adulthood. In this
      review, we highlight several studies that have revealed the role of epigenetics
      in multigenerational transmission of developmentally programmed obesity and
      associated cardiometabolic disease.

PMID- 28438345
TI  - Richter Syndrome With Extensive Isolated Pleural Extranodal Involvement: The
      Importance of PET/CT Imaging.

PMID- 28438346
TI  - Post-bronchodilator Reversibility of FEV1 and Eosinophilic Airway Inflammation in
      COPD.
AB  - INTRODUCTION: The relationship between bronchodilator responsiveness and
      eosinophilic airway inflammation has not been well documented in COPD. It has
      been investigated in this retrospective study. This issue has grown in importance
      due to increasing interest in the asthma-COPD overlap syndrome. METHODS: 264
      stable COPD patients with no past history of asthma were retrospectively
      analyzed. Correlation analyses between FEV1 reversibility and sputum eosinophil
      levels were conducted. Sputum eosinophil levels were dichotomized using FEV1
      reversibility cut-off points (>0.4L and >15% vs. >0.2L and >12%) and compared.
      The effectiveness of FEV1 reversibility to predict sputum eosinophilia (>3%) was
      analyzed with a logistic regression and a ROC analysis. RESULTS: 82 (31.1%)
      patients with higher FEV1 reversibility values (0.14 vs. 0.11L, P=.01) presented
      sputum eosinophilia. FEV1 reversibility was weakly correlated with the sputum
      eosinophil level (r=0.162, P=.008). Patients with FEV1>0.4L and >15% increment
      had higher sputum eosinophil levels (6.11 vs. 1.02%, P=.049) whereas the level
      did not differ when dichotomized by FEV1 increment >0.2L and >12%. Very positive
      FEV1 reversibility (>0.4L and >15%) predicted sputum eosinophilia after
      adjustment forage, baseline FEV1 and FVC (OR: 4.262, P=.029). In the ROC
      analysis, the AUC was 0.58 (P=.034), and FEV1 increment>0.4L and >15% had a
      positive predictive value of 63.6% and an overall accuracy of 70.1%. CONCLUSIONS:
      FEV1 reversibility was weakly correlated with sputum eosinophil levels in COPD.
      Positive FEV1 reversibility (>0.4L and >15%) is moderately successful in
      predicting sputum eosinophilia (>3%).

PMID- 28438347
TI  - Women's stated test preference on questionnaire versus their actual choice in
      real clinical setting regarding non-invasive prenatal test.

PMID- 28438348
TI  - Comment on "Risk factors for postoperative urinary tract infection following
      midurethral sling procedures".

PMID- 28438349
TI  - Hydrogen bonds in the vicinity of the special pair of the bacterial reaction
      center probed by hydrostatic high-pressure absorption spectroscopy.
AB  - Using the native bacteriochlorophyll a pigment cofactors as local probes, we
      investigated the response to external hydrostatic high pressure of reaction
      center membrane protein complexes from the photosynthetic bacterium Rhodobacter
      sphaeroides. Wild-type and engineered complexes were used with a varied number
      (0, 1 or 2) of hydrogen bonds that bind the reaction center primary donor
      bacteriochlorophyll cofactors to the surrounding protein scaffold. A pressure
      induced breakage of hydrogen bonds was established for both detergent-purified
      and membrane-embedded reaction centers, but at rather different pressures:
      between 0.2 and 0.3GPa and at about 0.55GPa, respectively. The free energy change
      associated with the rupture of the single hydrogen bond present in wild-type
      reaction centers was estimated to be equal to 13-14kJ/mol. In the mutant with two
      symmetrical hydrogen bonds (FM197H) a single cooperative rupture of the two bonds
      was observed corresponding to an about twice stronger bond, rather than a
      sequential rupture of two individual bonds.

PMID- 28438350
TI  - WITHDRAWN: MicroRNA-505 modulates cancer proliferation and migration in human non
      small cell lung cancer through inverse regulation of FZD4.
AB  - This article has been withdrawn at the request of the Editor-in-Chief. Following
      peer-review and acceptance of the above referenced paper for publication in Lung
      Cancer, the Editor-in-Chief was contacted by the Editor-in-Chief of the journal,
      Gene Therapy, with information that the manuscript had simultaneously been
      submitted to both Lung Cancer and Gene Therapy. A referee selected to review the
      manuscript for Gene Therapy was also contacted by the Editor-in-Chief of the
      journal, Respiratory Research, with a request to review the same manuscript for
      that journal. The three journals ascertained that the manuscript had been
      simultaneously submitted to all three journals. In addition, as part of their
      investigation of potential simultaneous submission, the Editors of Lung Cancer
      compared the manuscript submitted to Gene Therapy with that accepted for
      publication in Lung Cancer, and this has raised concerns related to the data
      presented in the paper. The paper accepted for publication in Lung Cancer
      examines A549 and H810 cells. The paper submitted to Gene Therapy examines A549
      and H510A cells. However, the data presented in both papers, including the
      figures, are identical. The Editors of Lung Cancer have asked the authors for an
      explanation, but the corresponding author has not responded. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 28438351
TI  - Fever and ulcerative-necrotic lesions in a 38 years old male.

PMID- 28438352
TI  - Burns to the genitalia, perineum, and buttocks increase the risk of death among
      U.S. service members sustaining combat-related burns in Iraq and Afghanistan.
AB  - PURPOSE: Among service members injured in Iraq and Afghanistan, to determine the
      risk of mortality associated with combat-related burns to the genitalia,
      perineum, and buttocks. MATERIALS AND METHODS: The prospectively maintained burn
      registry from the United States Army Institute of Surgical Research was
      retrospectively reviewed to identify all service members with combat-related
      burns sustained in Iraq and Afghanistan from March 2003 to October 2013. The two
      primary risk factors of interest were (1) any burn to the genitals, perineum,
      and/or buttocks (PB) and (2) burns involving the entire perineal, genital, and
      buttock region (complete PB). Cox proportional hazard models were used to
      estimate the risk of mortality for both primary risk factors, and adjusted for
      severe non-burn-related trauma, percent of burn over total body surface area
      (TBSA), inhalational injury, time to urinary tract infection, and time to
      bacteremia. A post-hoc analysis was performed to explore the potential effect
      modification of TBSA burned on the relationship between PB and mortality.
      RESULTS: Among the 902 U.S. service members with combat-related burns sustained
      during the study period, 226 (25.0%) had involvement of the genitalia, perineum,
      and/or buttocks. Complete PB was associated with a crude risk of mortality (HR:
      5.3; 2.9-9.7), but not an adjusted risk (HR=1.8; 0.8-4.0). However, TBSA burned
      was identified as a potential negative effect modifier. Among patients with burns
      <60% TBSA, sustaining a complete PB conferred an adjusted risk of death (HR=2.7;
      1.1-6.8). Further, patients with a perineal burn had a five-fold increased
      incidence of bacteremia. In adjusted models, each event of bacteremia increased
      the risk of mortality by 92% (HR 1.92; 1.39-2.65). Perineal burns were associated
      with a two-fold increased incidence of severe non-burn related trauma that also
      doubled mortality risk in adjusted models (HR 2.29; 1.23-4.27). CONCLUSIONS:
      Among those with relatively survivable combat-related burns (<60% TBSA),
      genital/perineal/buttock involvement increases the risk of death. Bacteremia may
      account for part of this increased risk, but does not fully explain the
      independent risk associated with perineal burns.

PMID- 28438353
TI  - The Role of Vitamin D in the Immune System as a Pro-survival Molecule.
AB  - PURPOSE: Vitamin D is a fascinating and attractive molecule that has gained
      particular attention in medicine in recent years. Its immunomodulatory and anti
      inflammatory potential might resemble the activity of many nature-derived
      molecules (eg, flavonoids), but its role in biology was selected during a long
      evolutionary pathway to dampen the damaging effect of cell stress response and of
      the immune reaction. In this sense, this molecule can be considered an ancient
      hormone that serves, in its primary role, as a pro-survival agent. The goal of
      this review was to elucidate this topic. METHODS: The article reviews current
      literature on the field, focusing on issues regarding the role of vitamin D in
      immunity. FINDINGS: Vitamin D participates in the survival machinery used by the
      cell, and in particular it plays a major role in synchronizing calcium
      oscillatory signaling to allow cell autophagy or apoptosis during a stress
      response. IMPLICATIONS: Vitamin D should be better highlighted in its molecular
      action and vitamin D receptor genomics to conceive a more suited therapeutic
      supplementation protocol in clinics.

PMID- 28438354
TI  - Coronary artery bypass graft surgery versus percutaneous coronary intervention
      with drug-eluting stents for left main coronary artery disease: A meta-analysis
      of randomized trials.
AB  - BACKGROUND: Despite several clinical studies, efficacy of coronary artery bypass
      grafting (CABG) surgery versus percutaneous coronary intervention (PCI) in
      patients with left main (LM) disease remains controversial. The objective of this
      meta-analysis of randomized trials was to evaluate the clinical outcome of CABG
      versus PCI with drug-eluting stents in LM coronary disease. METHODS: We
      systematically searched online databases up to March 2017 for randomized trials
      comparing CABG to PCI with drug-eluting stents. We calculated odds ratios (ORs)
      and 95% confidence intervals (CIs). RESULTS: We included data from 5 randomized
      trials and 4595 patients. At 30days, CABG was associated with higher stroke (OR
      2.54 [95% CI, 1.02-6.31]) and periprocedural myocardial infarction (OR 1.45 [95%
      CI, 1.00-2.10]), with no other significant differences compared to PCI. At 1year,
      CABG reduced repeat revascularization (OR 0.56 [95% CI, 0.40-0.77]), but
      increased stroke (OR 5.11 [95% CI, 1.62-16.12]). At 3-5years, CABG reduced repeat
      revascularization (OR 0.55 [95% CI, 0.45-0.67]) and non-periprocedural myocardial
      infarction (OR 0.45 [95% CI, 0.29-0.70]), without significant differences on
      other outcomes. CONCLUSIONS: From the present updated meta-analysis of available
      studies on LM coronary disease treatment, there were no differences in mortality,
      myocardial infarction, and stroke rate at 3-5years follow-up after CABG or PCI,
      but CABG decreased the rate of repeat revascularization and non-periprocedural
      infarction. However, at short-term follow-up, CABG showed higher rate of stroke
      and periprocedural myocardial infarction, but these effects attenuated over time.
      These findings merit further investigation at longer follow-up.

PMID- 28438355
TI  - Early and frequent defibrillator discharge in patients with cardiac sarcoidosis
      compared with patients with idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Little is known about the suitability of implantable cardioverter
      defibrillator (ICD) implantation in patients with cardiac sarcoidosis (CS). We
      evaluated the efficacy of ICD implantation in patients with CS, including
      suspected CS, compared with those with idiopathic dilated cardiomyopathy (DCM).
      METHODS: A total of 102 consecutive patients with definite CS, suspected CS, or
      DCM who underwent ICD implantation were enrolled. The endpoint was the first
      documentation of appropriate ICD therapy for ventricular tachyarrhythmias. The
      follow-up started after ICD implantation. RESULTS: Appropriate ICD therapies
      occurred in 15 (56%) of 27 patients with definite CS, 17 (68%) of 25 with
      suspected CS, and 16 (32%) of 50 with DCM. The rate of appropriate ICD therapies
      was higher in patients with definite CS and those with suspected CS than in those
      with DCM (log-rank test, p=0.010). After ICD implantation, five or more
      appropriate ICD therapies occurred in 5 (19%) patients with definite CS and 10
      (40%) with suspected CS, but in only 1 (2%) with DCM. Cox proportional hazard
      analysis showed that CS, including suspected CS, was independently associated
      with appropriate ICD therapies. For primary prevention, the rate of appropriate
      ICD therapies was higher in patients with CS than in those with DCM (log-rank
      test, p=0.034). More than half of patients with CS received appropriate ICD
      therapies. CONCLUSIONS: Patients with CS receive appropriate ICD therapies for
      ventricular tachyarrhythmias at a higher rate, compared with those with DCM,
      suggesting that ICD implantation should be performed in patients with CS.

PMID- 28438356
TI  - Rainfall increases the abundance of antibiotic resistance genes within a riverine
      microbial community.
AB  - Infections with antibiotic resistant bacteria are among the major threats for
      human health. Studies elucidating the role of the environment in their spread are
      still in their infancy, it, however, seems that different environments might
      function as a long-term reservoir of antibiotic resistance genes (ARGs) that
      reside within their microbial communities. An increasing number of studies target
      the presence and the persistence of ARGs in waters and soils that are exposed to
      human activities; they, however, rarely consider the spatial/temporal variability
      that predominate in these environments. Here we evaluated the effect of a
      moderate rain event (4 mm rain h-1) on the abundance and distribution of ARGs
      (tetA, ermB, blaCTXM, sulII, and qnrS), by comparing measurements of gene
      abundances during the rainfall to the yearly average, in the waters of a large
      subalpine river. ARG abundances, which all increased during the rain event, were
      then correlated to several microbiological, physical and chemical variables, in
      order to establish their potential origin. Increments in ARG abundances during
      rainfall (total ARGs: 24 fold) was concomitant to an increase in total
      phosphorous, N-NH4, and microbial aggregates. Our results show a strong influence
      of a moderate rainfall on the abundances of ARGs, and suggest the catchment as
      their source. The impact of moderate rainfalls in areas exposed to anthropic
      activities should then be considered in modelling and management of ARG dynamics.

PMID- 28438357
TI  - A neglected pathogen responsible for deep infections: A case report of
      spondylodiscitis due to Lactobacillus sp.

PMID- 28438358
TI  - Potential of oleaginous yeast Trichosporon sp., for conversion of sugarcane
      bagasse hydrolysate into biodiesel.
AB  - This study reports production of microbial oil from a yeast strain Trichosporon
      sp., (RW) isolated from decayed wood. Preliminary analysis based on fluorescence
      microscopy and spectroscopy of Nile red stained yeast cells showed accumulation
      of lipid globules. The potential of the yeast to produce lipids was evaluated on
      glucose, glycerol and acid hydrolysate of sugarcane bagasse, where Trichosporon
      sp. (RW) was found to accumulate 21.45 (59.6%), 18.41 (56%) and 10.25g/l (40.5%)
      of the lipids after 120h of fermentation at 30 degrees C. FAME analysis of lipids
      by GC-FID and NMR revealed oleic acid (18:1) as the major constituent,
      corresponding to 50.05, 46.48 and 54.66% of the accumulated lipids in glucose,
      glycerol and hydrolysate grown cultures, respectively. Other accumulated lipids
      included palmitic (16:0), linoleic (18:2) and stearic acids (18:0) in that order.
      The cetane number of the lipids ranged from 52.39 to 59.57 indicating suitability
      for biodiesel production.

PMID- 28438359
TI  - Impact of selectively enriched microbial communities on long-term fermentative
      biohydrogen production.
AB  - The effect of selectively enriched inoculum for biohydrogen production and shifts
      in microbial communities was observed using anaerobic sequencing batch reactor
      (AnSBR). Significantly, combined pretreatment using acid and iodopropane resulted
      3 fold increase in H2 production (8.65mol/kgCODR) over untreated control
      (2.63mol/kgCODR). Pretreatment showed significant shifts in the microbial
      communities which are thus accounted for enhanced H2 production. The high
      throughput pyrosequence analysis depicted shifts in phylum Firmicutes and
      Proteobacteria. In the case of Proteobacteria, there was an increase in
      Betaproteobacterial, decrease in Epsilonproteobacterial and compositional
      variation in Alphaproteobacterial species. The decreased OTU number after
      pretreatment indicate, reduction of undesirable microbial populations while
      favouring conditions for microbiome that are involved in acidogenic, acetogenic
      and H2 production.

PMID- 28438360
TI  - [Tuberculosis in adolescents in Brazzaville].

PMID- 28438361
TI  - Influence of distal entry tears in acute type B aortic dissection after thoracic
      endovascular aortic repair.
AB  - OBJECTIVE: This study evaluated the clinical influence of distal entry tears in
      acute type B aortic dissection (ATBAD) after thoracic endovascular aortic repair
      (TEVAR). METHODS: From August 2009 to December 2014, the clinical outcomes of 130
      patients who underwent TEVAR for ATBAD were retrospectively analyzed. According
      to whether distal entry tears existed after TEVAR, patients were divided into
      group A (n = 25, absence of distal entry tears) and group B (n = 105, presence of
      distal entry tears). We evaluated clinical outcomes, including mortality and
      morbidity in early and late follow-up, as well as aortic remolding. Late aortic
      events were defined as aortic dissection-related events occurring >30 days from
      the initial TEVAR procedures, which consisted of endoleak, retrograde type A
      aortic dissection, aortic enlargement, late rupture, repeat dissection, and stent
      induced new entry tear. RESULTS: The study comprised 130 patients (114 men
      [87.7%] and 16 women [12.3%)] with a mean age of 53.71 years. The 30-day
      mortality was 3.1%, and early morbidity included type I endoleak, 3.1%, organ
      failure, 3.8%; stroke, 3.1%; spinal cord ischemia, 0%; and early rupture 1.5%.
      The overall survival rate by Kaplan-Meier analysis at 1, 3, and 5 years was
      93.8%, 89.5%, and 79.2%, respectively. There were no significant differences in
      early morbidity and 30-day mortality and late survival between group A and group
      B. However, group A had a significantly lower rate of late aortic events than
      group B (P = .028 by log-rank test). Meanwhile, group A had better aortic
      remolding than group B in complete thrombosis of the thoracic aorta at 12 months
      postoperatively (100% vs 83.5%; P = .029). CONCLUSIONS: This study demonstrated
      that TEVAR for ATBAD had low perioperative morbidity and mortality and
      satisfactory midterm outcome. Distal entry tears increase the occurrence of late
      aortic events and inhibit aortic remolding but do not have a significantly
      negative effect on late survival. Repairing all entry tears to restore single
      lumen blood flow and enhance false lumen thrombosis might benefit selected
      patients.

PMID- 28438362
TI  - Bypass of an anesthesiologist-directed preoperative evaluation clinic results in
      greater first-case tardiness and turnover times.
AB  - STUDY OBJECTIVE: We evaluated 4 hypotheses related to bypass of an
      anesthesiologist-directed preoperative evaluation clinics (APEC): 1) first-case
      tardiness and turnover times increased; 2) turnover times increased more than
      first-case tardiness; and higher American Society of Anesthesiologists Physical
      Status (ASA PS) resulted in both an ordered increase among ASA PS and within ASA
      PS in 3) first-case tardiness; and 4) turnover times. DESIGN: Retrospective
      observational study using electronic health records. SETTING: One large, teaching
      hospital. PATIENTS: An average of 14,310 patients per year undergoing elective
      surgery in the hospital's main opera rating rooms who were not inpatients
      preoperatively between 2006 and 2016. INTERVENTIONS: None. MEASUREMENTS: Average
      increases in first-case tardiness and turnover times between patients seen or not
      seen preoperatively in the APEC. MAIN RESULTS: APEC bypass increased first-case
      tardiness 2.58 min per case (CI 1.55-3.61; P<0.0001) and turnover times by 7.49
      min (CI 6.79-8.19; P<0.0001). The increase in mean turnover time was greater than
      mean first-case tardiness (difference=4.91 min; CI 3.76-6.06; P<0.0001). Had all
      patients bypassed the APEC, the increase in total minutes OR- 1 workday- 1 for
      turnover times would have been larger than the increase in first-case tardiness
      (difference=5.71, CI 3.17-4.72; P<0.0001). There was an ordered increase with
      APEC bypass for both first-case tardiness and turnover times with increasing ASA
      PS (P<0.0001). Within ASA PS, first-case tardiness (all P-values<0.003) and
      turnover times (all P-values<0.0001) also increased with APEC bypass. All 4
      hypotheses were accepted. CONCLUSIONS: Overall and with control for ASA PS, APEC
      bypass increases first-case tardiness and turnover times. A strategy of selective
      bypass of ASA PS 1-2 patients would not be effective economically because of
      substantial delays from ASA PS 2 patients.

PMID- 28438363
TI  - A brief history of amoebic liver abscess with an illustrative case.

PMID- 28438364
TI  - Cross cultural training in primary mental health care consultations in Moldova -
      The tEACH perspective.
AB  - OBJECTIVE: This article reports experiences and challenges encountered in a cross
      cultural training project in Moldova that was undertaken by tEACH, the teaching
      subcommittee of EACH: International Association for Communication in Healthcare,
      in cooperation with local and international stakeholders. As part of a major
      health policy reform, the aim was to equip a group of trainers with the skills to
      train Moldovan professionals in skills for primary mental health care, including
      communication skills. METHODS: The project consisted of 3 weeks of training using
      mainly experiential teaching methods to allow participants to practice content
      and methods, including interactive lecturing, roleplay, feedback and video.
      RESULTS: A majority of the participants reported that they acquired key
      facilitation skills. They valued the opportunity to practice and receive
      feedback. However, some reported that there was too much focus on communication
      skills, which was thought to be less relevant in a Moldovan context. Furthermore
      our learner-centered approach was occasionally experienced as a lack of structure
      CONCLUSION: The tEACH expertise plays an important role in supporting trainers in
      cross-cultural contexts with effective communication skills methods. PRACTICE
      IMPLICATIONS: Teaching in a cross-cultural context is only successful through
      continuous dialogue with stakeholders and demands attention to cultural
      differences.

PMID- 28438366
TI  - Current status and future expectations in treatment of bone and soft tissue
      sarcoma.

PMID- 28438365
TI  - Protein conformational dynamics studied by 15N and 1H R1rho relaxation
      dispersion: Application to wild-type and G53A ubiquitin crystals.
AB  - Solid-state NMR spectroscopy can provide site-resolved information about protein
      dynamics over many time scales. Here we combine protein deuteration, fast magic
      angle spinning (~45-60kHz) and proton detection to study dynamics of ubiquitin in
      microcrystals, and in particular a mutant in a region that undergoes microsecond
      motions in a beta-turn region in the wild-type protein. We use 15N R1rho
      relaxation measurements as a function of the radio-frequency (RF) field strength,
      i.e. relaxation dispersion, to probe how the G53A mutation alters these dynamics.
      We report a population-inversion of conformational states: the conformation that
      in the wild-type protein is populated only sparsely becomes the predominant
      state. We furthermore explore the potential to use amide-1H R1rho relaxation to
      obtain insight into dynamics. We show that while quantitative interpretation of
      1H relaxation remains beyond reach under the experimental conditions, due to
      coherent contributions to decay, one may extract qualitative information about
      flexibility.

PMID- 28438367
TI  - The effect of dietary supplements on clinical aspects of autism spectrum
      disorder: A systematic review of the literature.
AB  - BACKGROUND: Autism spectrum disorder is associated with significant social and
      financial burden and no definite treatment for this entity has been identified,
      yet. In recent years there has been an increasing interest in the use of dietary
      interventions as a complementary therapeutic option for these patients.
      OBJECTIVE: The aim of this systematic review is to provide high evidence level
      literature data about the effect of dietary supplements on clinical aspects of
      children with autism. METHODS: A comprehensive literature search was conducted
      using Pubmed as the medical database source. Randomized controlled trials
      conducted in pediatric populations and including measures of clinical outcomes
      were considered. RESULTS: A total of 17 eligible prospective studies were
      selected. Types of dietary supplements evaluated in these studies included amino
      acids, fatty acids and vitamins/minerals. N-acetylcysteine was shown to exert a
      beneficial effect on symptoms of irritability. On the other hand, literature data
      about the efficacy of d-cycloserine and pyridoxine-magnesium supplements was
      controversial. No significant effect was identified for fatty acids, N,N
      dimethylglycine and inositol. Literature data about ascorbic acid and methyl B12
      was few, although some encouraging results were found. No serious adverse events
      were reported in the vast majority of the studies, while the prevalence of
      adverse reactions was similar between treatment and placebo groups. CONCLUSIONS:
      The use of dietary supplements in children with autism seems to be a safe
      practice with encouraging data about their clinical efficacy. More studies are
      needed to further investigate this issue.

PMID- 28438368
TI  - Early infantile presentation of 3-methylglutaconic aciduria type 1 with a novel
      mutation in AUH gene: A case report and literature review.
AB  - 3-Methylglutaconic aciduria is a member of inborn errors of leucine metabolism
      pathway. 3-Methylglutaconic aciduria type I (MGA1) causes neurological problems
      which are present during infancy or childhood but the diagnosis may be delayed
      until adulthood. Here we report a 3years old patient with developmental delay
      from a relative parent's that his medical evaluations include analyses of urinary
      organic acid and blood acylcarnitine showed high level of 3-methylglutacoic acid,
      3-hydroxyisovaleric acid and increased level of 3-hydroxyisovalerylcarnitine
      respectively. Further evaluation and genetic tests revealed a novel homozygous
      mutation of variant c.179del G (p.Gly60Valfs*12) in exon 1 of the AUH gene that
      was compatible with the diagnosis of MGA1. In segregation analysis of his family,
      both parents were heterozygous for the respective mutation, confirming obligate
      parental carrier status and segregation of the mutation.

PMID- 28438369
TI  - Independent prognostic importance of respiratory instability and sympathetic
      nerve activity in patients with chronic heart failure.
AB  - BACKGROUND: Respiratory instability in chronic heart failure (CHF) is
      characterized by irregularly rapid respiration or non-periodic breathing rather
      than by Cheyne-Stokes respiration. We developed a new quantitative measure of
      respiratory instability (RSI) and examined its independent prognostic impact upon
      CHF. METHODS: In 87 patients with stable CHF, respiratory flow and muscle
      sympathetic nerve activity (MSNA) were simultaneously recorded. RSI was
      calculated from the frequency distribution of respiratory spectral components and
      very low frequency components. RESULTS: During a mean follow-up of 85+/-38
      months, 24 patients died. Sixteen patients who died of cardiac causes had a lower
      RSI (16+/-6 vs. 30+/-21, p<0.01), a lower specific activity scale (4.3+/-1.4 Mets
      vs. 5.7+/-1.4 Mets, p<0.005), a higher MSNA burst area (16+/-5% vs. 11+/-4%,
      p<0.001), and a higher brain natriuretic peptide (BNP) level (514+/-559pg/ml vs.
      234+/-311pg/ml, p<0.05) than 71 patients who did not die of cardiac causes.
      Multivariate analysis revealed that RSI (p=0.015), followed by MSNA burst area
      (p=0.033), was an independent predictor of subsequent all-cause deaths and that
      RSI (p=0.026), MSNA burst area (p=0.001), and BNP (p=0.048) were independent
      predictors of cardiac deaths. Patients at very high risk of fatal outcome could
      be identified by an RSI<20. CONCLUSIONS: The daytime respiratory instability
      quantified by a new measure of RSI has prognostic importance independent of
      sympathetic nerve activation in patients with clinically stable CHF. An RSI of
      <20 identifies patients at very high risk for subsequent all-cause and
      cardiovascular death.

PMID- 28438370
TI  - Risk factors for noninvasive ventilation failure in patients with acute
      cardiogenic pulmonary edema: A prospective, observational cohort study.

PMID- 28438371
TI  - Noninvasive ventilation for ARDS in patients with cancer: Still possible or there
      continues to be a learning curve?

PMID- 28438372
TI  - Comment on Rishu et al. Time required to initiate outbreak and pandemic
      observational research.

PMID- 28438373
TI  - Geriatric nutritional risk index as a nutritional and survival risk assessment
      tool in stable outpatients with systolic heart failure.
AB  - BACKGROUND AND AIMS: Malnutrition is frequent in heart failure (HF). However, the
      best tool for evaluating malnutrition in geriatric patients with HF with reduced
      ejection fraction (HFrEF) is unknown. This study aimed to evaluate the
      incremental prognostic value of the geriatric nutritional risk index (GNRI) in
      stable geriatric outpatients with HFrEF compared with a clinical/laboratory
      prognostic model. METHODS AND RESULTS: A total of 143 outpatients with HFrEF,
      aged >65 years, a LVEF <40%, and who were stable and on optimal therapy were
      studied. Follow-up lasted 3 years. The outcome was all-cause death. The GNRI was
      calculated as follows: [(1.489 * serum albumin (g/L)) + (41.7 * (current body
      weight/ideal weight)]. The 3-year death rate was 36.4% and 16 (11.2%) patients
      were at risk of malnutrition (GNRI <=98). Deceased patients had a lower GNRI
      (113.6 +/- 9.1 vs. 105.6 +/- 9.2; p < 0.001) than did survivors. Greater values
      of the GNRI (hazard ratio = 0.93, 95% confidence interval [CI] = 0.90-0.95; p <
      0.001) and GNRI >98 (hazard ratio = 0.29, 95% CI 0.15-0.57; p < 0.001) were
      associated with better survival. These factors remained significant after
      adjustment of significant confounders. The GNRI was a better discriminator of
      death than weight and albumin. Adding the GNRI to the clinical/laboratory
      predictor survival model significantly increased the c-statistics from 0.93 to
      0.95 (p < 0.001) and the chi-square likelihood ratio test from 106.15 to 119.9.
      CONCLUSION: The risk of malnutrition, as assessed by the GNRI, in stable
      geriatric outpatients with HFrEF is a strong independent predictor of survival.
      The GNRI adds significant prognostic information to the clinical/laboratory
      model.

PMID- 28438374
TI  - Validity of Self-Assessed Sexual Maturation Against Physician Assessments and
      Hormone Levels.
AB  - OBJECTIVE: To compare self-report and physician assessments of sexual maturation
      against serum hormone markers to evaluate the hypothesis that the validity of
      self-assessed sexual maturation is underestimated in traditional validation
      studies. STUDY DESIGN: We adapted a self-assessment instrument that 248 Mexican
      children and adolescents, aged 8-13 years, completed. The participants were
      examined by a trained pediatrician and provided fasting blood samples for
      measurement of reproductive hormones (eg, testosterone, estradiol, sex hormone
      binding globulin, inhibin B) and other hormones (eg, C-peptide, insulin-like
      growth factor 1, leptin, dehydroepiandrosterone sulfate) known to change during
      adolescence. Spearman correlations (r) were calculated among the average rank of
      all hormones and self-assessed and physician-assessed Tanner stage. The method of
      triads was used to assess the validity of self-reports by estimating correlations
      between self-assessments and true but unobservable sexual maturation based on all
      available data. Bootstrap sampling was used to construct 95% CIs. RESULTS: The
      validity of self-reported genitalia staging for boys was modest (r = 0.50; 95%
      CI,  0.31-0.65) and inferior to physician assessment (r = 0.75; 95% CI, 0.56
      0.93). Breast stage was well reported (r = 0.89; 95% CI, 0.79-0.97) and superior
      to physician assessment (r = 0.80; 95% CI, 0.70-0.89). Pubic hair stage reported
      by boys (r = 0.91; 95% CI, 0.79-0.99) and girls (r = 0.99; 95% CI, 0.96-1.00) was
      superior to physician assessment (r = 0.79; 95% CI, 0.57-0.97 and r = 0.91; 95%
      CI, 0.83-0.97, respectively). CONCLUSION: Self-assessment can be validly used in
      epidemiologic studies for evaluating sexual maturation in children; however,
      physician assessment may be necessary for accurate assessment of genitalia
      development in boys.

PMID- 28438375
TI  - Racial and Ethnic Differences in Pediatric Readmissions for Common Chronic
      Conditions.
AB  - OBJECTIVE: To compare the timing and magnitude of variation of pediatric
      readmission rates across race/ethnicity for selected chronic conditions: asthma,
      diabetes, seizures, migraines, and depression. STUDY DESIGN: Retrospective
      analysis of hospitalizations at 48 children's hospitals in the 2013 Pediatric
      Health Information System database for children (ages 0-18 years) admitted for
      asthma (n = 36 910), seizure (n = 35 361), diabetes (n = 12 468), migraine (n =
      5882), and depression (n = 5132). Generalized linear models with a random effect
      for hospital were used to compare the likelihood of readmission by patients'
      race/ethnicity, adjusting for severity of illness, age, payer, and medical
      complexity. Adjusted readmission rates were calculated by week over 1 year.
      RESULTS: Significant variation in adjusted readmission rates by race/ethnicity
      existed for conditions aside from depression. Disparities for diabetes and asthma
      emerged at 3 and 4 weeks, respectively; they remained divergent up to 1 year with
      the highest 1-year readmission rates in non-Hispanic blacks vs other
      race/ethnicities (diabetes: 21.7% vs 13.4%, P < .001; asthma: 21.4% vs 14.6%, P <
      .001). Disparities for migraines and seizure emerged at 6 and 7 weeks,
      respectively; they remained up to 1 year, with the highest 1-year readmission
      rates in non-Hispanic whites vs other race/ethnicities (migraine: 17.3% vs 13.6%,
      P < .001; seizure: 23.9% vs 21.9%, P < .001). CONCLUSIONS: Readmission
      disparities behave differently across chronic conditions. They emerge more
      quickly after discharge for children hospitalized with asthma or diabetes than
      for seizures or migraines. The highest readmission rates were not consistently
      observed for 1 particular race/ethnicity. Study findings can impact pediatric
      chronic disease management to improve care for children with these conditions.

PMID- 28438376
TI  - Current Trends in the Use of Two Combination Antifungal/Corticosteroid Creams.
AB  - Superficial fungal infections are among the most commonly managed skin problems
      by general practitioners. Although evidence shows combination
      antifungal/corticosteroid topicals are more expensive and less effective than
      single-agent antifungals, practitioners continue to prescribe combination agents.
      We examined current prescription trends of 2 combination
      antifungal/corticosteroid medications, Lotrisone and Mycolog-II.

PMID- 28438377
TI  - Efficacy and Safety of Lactobacillus plantarum DSM 9843 (LP299V) in the
      Prevention of Antibiotic-Associated Gastrointestinal Symptoms in Children
      Randomized, Double-Blind, Placebo-Controlled Study.
AB  - OBJECTIVES: To determine if Lactobacillus plantarum DSM9843 (LP299V) reduces the
      frequency of antibiotic-associated loose/watery stools and gastrointestinal
      symptoms, and can be administered safely to children who are prescribed
      antibiotics. STUDY DESIGN: We performed a prospective, double-blind, randomized,
      placebo-controlled, multicenter, parallel-group study in children receiving
      outpatient antibiotic therapy in primary healthcare settings. The children were
      given LP299V/placebo during the antibiotic therapy and for 1 week after the end
      of treatment. The primary outcome measure was the incidence of at least 1
      loose/watery stool (type 6 or 7 according to the Bristol Stool Form Scale).
      Gastrointestinal symptoms (abdominal pain, abdominal distention, vomiting, and
      flatulence) were followed up until 1 week after the last intake of the study
      product. RESULTS: A total of 438 children (male: 235, female: 203) aged 1-11
      years (mean +/- SD: 5.2 +/- 2.7) were randomized to receive LP299V (N = 218) or
      placebo (N = 220). The incidence of loose/watery stools in the 2 study groups
      (LP299V and placebo) was similar, 39% vs 44.5% respectively (P = .26) as was the
      mean number of loose/watery stools (3.9 +/- 3.5 vs 4.7 +/- 6.3; P = .9).
      Antibiotic-associated diarrhea (defined as >=3 loose/watery stools/24 hours
      starting from 2 hours after initiation of antibiotic treatment until the end of
      the study) occurred in 2.8% of the subjects receiving LP299V compared with 4.1%
      in the placebo arm (P = .4). The number of children with abdominal symptoms did
      not differ between the groups. CONCLUSIONS: No beneficial effect of LP299V
      compared with placebo was observed for the incidence of loose/watery stools, mean
      number of loose/watery stools, or the incidence of abdominal symptoms. LP299V had
      a satisfactory safety profile. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01940913.

PMID- 28438379
TI  - Department of Error.

PMID- 28438378
TI  - Genotyping of the human papilloma virus in a group of Mexican women treated in a
      highly specialist hospital: Multiple infections and their potential transcendence
      in the current vaccination programme.
AB  - BACKGROUND AND OBJETIVE: Human papilloma virus (HPV) is one of the main risk
      factors associated with the development of cervical cancer and its precursor
      lesions. It has been reported that HPV16 and 18 types cover approximately 70% of
      cervical cancer worldwide; however, significant variation in percentages of HPV
      infections could be related to specific populations. MATERIALS AND METHODS:
      Purified DNA of 67 cervical samples were analyzed by Linear Array(r) HPV
      genotyping kit. These analyzed samples correspond to 19 cervical tumors, 15 high
      grade squamous intraepithelial lesions, 20 low-grade squamous intraepithelial
      lesions, and 13 cervical samples without injury were studied, all of them
      previously diagnosed. RESULTS: In general, 16 different HPV types were found with
      differences in their frequencies, cervical invasive cancer being the richest in
      HPV sequences, followed by the low-grade squamous intraepithelial lesions and
      then high-grade lesions. HPV16 was the most frequently distributed type in
      neoplastic lesions of the cervix, followed by the HPV52, suggesting viral type
      variability, probably associated to the geographical region studied. CONCLUSIONS:
      The results could indicate variability in HPV presence in Mexico, underlining the
      important role for HPV52 among others in the Mexican population. This would also
      potentially have an impact on the current anti-HPV vaccination schemes.

PMID- 28438380
TI  - The role of muscle strengthening in exercise therapy for knee osteoarthritis: A
      systematic review and meta-regression analysis of randomized trials.
AB  - OBJECTIVES: To analyze if exercise interventions for patients with knee
      osteoarthritis (OA) following the American College of Sports Medicine (ACSM)
      definition of muscle strength training differs from other types of exercise, and
      to analyze associations between changes in muscle strength, pain, and disability.
      METHODS: A systematic search in 5 electronic databases was performed to identify
      randomized controlled trials comparing exercise interventions with no
      intervention in knee OA, and reporting changes in muscle strength and in pain or
      disability assessed as standardized mean differences (SMD) with 95% confidence
      intervals (95% CI). Interventions were categorized as ACSM interventions or not
      ACSM interventions and compared using stratified random effects meta-analysis
      models. Associations between knee extensor strength gain and changes in
      pain/disability were assessed using meta-regression analyses. RESULTS: The 45
      eligible trials with 4699 participants and 56 comparisons (22 ACSM interventions)
      were included in this analysis. A statistically significant difference favoring
      the ACSM interventions with respect to knee extensor strength was found [SMD
      difference: 0.448 (95% CI: 0.091-0.805)]. No differences were observed regarding
      effects on pain and disability. The meta-regressions indicated that increases in
      knee extensor strength of 30-40% would be necessary for a likely concomitant
      beneficial effect on pain and disability, respectively. CONCLUSION: Exercise
      interventions following the ACSM criteria for strength training provide superior
      outcomes in knee extensor strength but not in pain or disability. An increase of
      less than 30% in knee extensor strength is not likely to be clinically beneficial
      in terms of changes in pain and disability (PROSPERO: CRD42014015344).

PMID- 28438381
TI  - Avascular bone necrosis: An underestimated complication of systemic sclerosis.

PMID- 28438382
TI  - Monocentric experience of the rituximab therapy in systemic lupus erythematosus
      associated antiphospholipid syndrome with warfarin therapy failure.

PMID- 28438383
TI  - Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome
      induced by nivolumab.
AB  - INTRODUCTION: A new articular syndrome described as immunrelated side effect of
      immunotherapy: PD-1 inhibitors have revolutionized the treatment of advanced
      melanoma but are responsible for immune-related toxicity. We report a case of
      remitting seronegative symetrical synovitis with pitting edema (RS3PE) syndrome
      induced by nivolumab. CASE REPORT: A 80 year-old man with stage IV BRAF-wild type
      and NRAS exon 2-mutated melanoma was treated first line by nivolumab 3mg/kg every
      2 weeks. At week 4, before the 3rd infusion, he presented with inflammatory
      arthralgia, synovitis of proximal interphalangeal, wrist and ankle joints, and
      edema of both hands and forearms. Laboratory tests showed inflammatory syndrome
      (CRP = 8.4mg/dL), negative rheumatoid factor, and anti-CCP antibodies.
      Radiographs did not show any joint erosion but joint ultrasound displayed intra
      articular effusion and tenosynovitis. PET/CT performed 6 and 3 months before
      treatment for melanoma work-up showed an isolated hypermetabolism of the shoulder
      girdle. The diagnosis of RS3PE was retained. A systemic corticosteroid treatment
      (0.5mg/kg/d) was initiated; nivolumab was hold during 4 weeks leading to
      remission of clinical symptoms within 10 days, CRP level normalization and
      without relapse when nivolumab was resumed. Corticosteroids were progressively
      tapered and stopped after 9 months. After 5 months, anti-PD1 was definitively
      stopped because of disease progression. CONCLUSION: With this atypical case,
      clinicians should remain alert on a whole range of autoimmune diseases
      susceptible to be induced.

PMID- 28438384
TI  - Evaluation of vitamin D levels in patients with chronic low back-leg pain.
AB  - OBJECTIVE: We aimed to examine the relationship between the levels of vitamin D
      and patients with chronic low back-leg pain (CLBLP) and to investigate its
      effects on pain and functional capacity. METHODS: 145 patients
      (female/male:103/42) with CLBLP, aged between 35 and 65 years (mean age: 53,06 +/
      8,14), participated in the study. Visual Analog Pain Scale (VAS) was used to
      measure the state of pain. Pain-related functional capacity was evaluated through
      Oswestry Disability Index (ODI). Patients were classified into three groups based
      on their serum vitamin D levels: normal (>=30 ng/ml), vitamin D insufficiency (21
      29 ng/ml), and vitamin D deficiency (<=20 ng/ml). RESULTS: We found that 22,8% of
      patients (n:33) had vitamin D deficiency, 42,8% (n:62) had vitamin D
      insufficiency, and 34,5% (n:50) had normal levels of vitamin D. VAS scores were
      4,75 +/- 0,93; 4,66 +/- 0,97 and 4,52 +/- 0,90 for patients with vitamin D
      deficiency, vitamin D insufficiency, and normal levels of vitamin D,
      respectively. We found that there was no significant relationship between vitamin
      D level and VAS score (p>0,05). ODI scores were 18,78 +/- 7,89; 15,46 +/- 5,57
      and 14,52 +/- 7,19 for patients with vitamin D deficiency, vitamin D
      insufficiency, and normal levels of vitamin D, respectively. CLBLP-related
      functional capacity was found to be significantly lower in patients with vitamin
      D deficiency when compared to other two groups (p < 0,05). CONCLUSION: Vitamin D
      deficiency may lead to lower functional capacity, and clinically, Vit D levels
      should be checked in musculoskeletal pain patients at risk of Vit D deficiency.
      LEVEL OF EVIDENCE: Level IV, Diagnostic study.

PMID- 28438385
TI  - Small molecules inhibit STAT3 activation, autophagy, and cancer cell anchorage
      independent growth.
AB  - Triple-negative breast cancers (TNBCs) lack the signature targets of other breast
      tumors, such as HER2, estrogen receptor, and progesterone receptor. These
      aggressive basal-like tumors are driven by a complex array of signaling pathways
      that are activated by multiple driver mutations. Here we report the discovery of
      6 (KIN-281), a small molecule that inhibits multiple kinases including maternal
      leucine zipper kinase (MELK) and the non-receptor tyrosine kinase bone marrow X
      linked (BMX) with single-digit micromolar IC50s. Several derivatives of 6 were
      synthesized to gain insight into the binding mode of the compound to the ATP
      binding pocket. Compound 6 was tested for its effect on anchorage-dependent and
      independent growth of MDA-MB-231 and MDA-MB-468 breast cancer cells. The effect
      of 6 on BMX prompted us to evaluate its effect on STAT3 phosphorylation and DNA
      binding. The compound's inhibition of cell growth led to measurements of
      survivin, Bcl-XL, p21WAF1/CIP1, and cyclin A2 levels. Finally, LC3B-II levels
      were quantified following treatment of cells with 6 to determine whether the
      compound affected autophagy, a process that is known to be activated by STAT3.
      Compound 6 provides a starting point for the development of small molecules with
      polypharmacology that can suppress TNBC growth and metastasis.

PMID- 28438386
TI  - Catabolism of antibody drug conjugates and characterization methods.
AB  - Antibody drug conjugates (ADCs) are large molecule therapeutics in which a
      cytotoxic payload is conjugated to a monoclonal antibody (mAb) via a linker. The
      molecules are designed to selectively bind to target-expressing cells, thus
      delivering therapeutic agents directly to the tumor. Chemical and enzymatic
      stability prior to reaching the target is an important factor for ADCs since it
      impacts their safety, efficacy, and pharmacokinetics (PK). One of the main
      reasons for off-target effects of ADCs is premature release of cytotoxic agents,
      either in the blood stream or at non-specific sites. Once an ADC is internalized
      by target-expressing cells, the cytotoxic payload and/or related catabolites are
      released through chemical or enzymatic cleavage within the cells. In some cases,
      the released payload and/or catabolites are effluxed into the systemic
      circulation and follow a small molecule disposition path. Since doses of ADCs are
      low, the concentration of cytotoxic payload and related catabolites/metabolites
      range from ng to MUg levels in systemic circulation or tumors in clinical
      studies. Hence, it is challenging to identify these species without prior
      knowledge of the pathways of catabolism. The current review summarizes the
      mechanism of cleavage/catabolism of various types of linkers and available in
      vitro, in vivo, and bioanalytical methods for evaluation of catabolism of ADCs.

PMID- 28438388
TI  - Kaposiform haemangioendothelioma: a review with emphasis on histological
      differential diagnosis.
AB  - Kaposiform haemangioendothelioma (KHE) is a rare, locally aggressive/borderline
      vascular tumour primarily seen in neonates and children. KHE is occasionally
      associated with Kasabach-Merritt phenomenon and tends to have a poor clinical
      prognosis. While the histological features of tufted angiomas and KHE overlap,
      some believe tufted angiomas are a milder, benign, more localised counterpart of
      KHE. The other histological differential diagnoses of KHE include infantile
      haemangioma, congenital haemangioma, spindle cell haemangioma, verrucous
      malformation/haemangioma, and Kaposi sarcoma. Microscopically, KHE is
      characterised by confluent nodules of neoplastic spindled endothelial cells
      involving multiple planes of tissue which are positive for endothelial,
      lymphatic, and smooth muscle markers. Resection, once thought to be the
      definitive treatment for KHE, is often unattainable due to the extent of the
      lesion; thus, single or combination chemotherapies have been used to treat these
      patients. Sirolimus has recently been reported to be a successful agent to treat
      refractory and complicated cases of KHE.

PMID- 28438389
TI  - Gastric perineurioma: clinicopathological characteristics.

PMID- 28438387
TI  - Structural Insights into the Mechanism of Group II Intron Splicing.
AB  - While the major architectural features and active-site components of group II
      introns have been known for almost a decade, information on the individual stages
      of splicing has been lacking. Recent advances in crystallography and cryo
      electron microscopy (cryo-EM) have provided major new insights into the structure
      of intact lariat introns. Conformational changes that mediate the steps of
      splicing and retrotransposition are being elucidated, revealing the dynamic,
      highly coordinated motions that are required for group II intron activity.
      Finally, these ribozymes can now be viewed in their larger, more natural context
      as components of holoenzymes that include encoded maturase proteins. These
      studies expand our understanding of group II intron structural diversity and
      evolution, while setting the stage for rigorous mechanistic analysis of RNA
      splicing machines.

PMID- 28438390
TI  - Anaemia and 'triple-negative' bone marrow fibrosis: a diagnostic conundrum.

PMID- 28438391
TI  - Myoid neoplasm with lipoblast-like cells and haemangiopericytoma pattern: an
      unusual manifestation of EBV associated myoid tumour.

PMID- 28438392
TI  - Immunohistochemical detection of PD-L1 for research studies: which antibody and
      what protocol?

PMID- 28438393
TI  - Use of the EntericBio Gastro Panel II in a diagnostic microbiology laboratory:
      challenges and opportunities.
AB  - We sought to verify the performance of the EntericBio real-time Gastro Panel 2
      (GP2; Serosep, Ireland) assay targeting Salmonella, Shigella, Campylobacter,
      verotoxin producing E. coli (VTEC), Giardia, and Cryptosporidium in a high
      throughput diagnostic laboratory. Following a technical verification period where
      237 faecal samples were tested in parallel, guided culture and discrepancy
      analysis were performed. A total of 13,223 faecal samples were screened by the
      GP2 assay. During technical verification, sensitivity, specificity, negative and
      positive predictive value of the GP2 assay compared with conventional methods
      were 100% (83-100%), 98% (96.7-98.2%), 100% (98.5-100%), and 82.6% (69-83%),
      respectively. With guided culture, specificity (99.4-100%) and positive
      predictive value (15-100%) varied by target. Challenges with interpretation of
      results, particularly for VTEC, Shigella and Salmonella, are discussed.

PMID- 28438394
TI  - Gastric foveolar dysplasia: a survey of reporting habits and diagnostic criteria.
AB  - This study aimed to ascertain views, incidence of reporting and diagnostic
      criteria for gastric foveolar dysplasia. A questionnaire, a post-questionnaire
      discussion and microscopic assessment of selected cases was conducted by
      gastrointestinal pathologists to explore the above-stated aims. Fifty-four
      percent of respondents never or rarely diagnosed gastric foveolar-type dysplasia.
      The general consensus was that round nuclei, lack of nuclear stratification,
      presence of inflammation/damage and surface maturation favoured reactive change;
      while architectural abnormalities/complexity and nuclear enlargement mainly were
      used to separate low-grade from high-grade foveolar dysplasia.
      Immunohistochemistry was rarely used to make the diagnosis of dysplasia and was
      thought not to be of help in routine practice. Inter-observer agreement in
      grading of dysplasia versus reactive, and the type of dysplasia (foveolar versus
      adenomatous), was substantial/almost perfect amongst 35.7% and 21.4% of
      participants, respectively. This reflects low reproducibility in making these
      diagnoses. In conclusion, foveolar dysplasia was a rarely made diagnosis among 14
      gastrointestinal pathologists, there are no uniform criteria for diagnosis and
      there is poor inter-observer agreement in separating low-grade foveolar dysplasia
      from reactive gastric mucosa and low-grade adenomatous dysplasia. Greater
      awareness and agreed criteria will prevent misdiagnosis of low-grade foveolar
      dysplasia as reactive, and vice versa.

PMID- 28438395
TI  - Motivation for orthognathic treatment and anticipated satisfaction levels-a two
      centre cross-national audit.
AB  - PURPOSE: This audit investigated factors which motivate patients to seek
      orthognathic treatment, assessed how confident patients were that they would be
      satisfied with the outcome of treatment, and explored possible influencing
      factors. MATERIALS AND METHODS: Questionnaires were distributed to pre-surgical
      patients at two centres (United Kingdom and Switzerland); questions asked what
      patients wished to gain from orthognathic treatment and how confident they were
      that they would be satisfied with treatment outcome. Gender, age and location
      were recorded as demographic variables, and type of malocclusion was also
      recorded. RESULTS: A total of 202 questionnaires were returned (UK, n = 149;
      Switzerland, n = 53). Reported motivating factors focused on improvements in
      aesthetics (specified and unspecified) (UK vs. Switzerland: 91.3% vs. 83.0%),
      function (72.5% vs. 66.0%), psychosocial health (51.7% vs. 20.8%), speech (4.0%
      vs. 7.5%), alleviation of pain (5.4% vs. 17%) and normalization of breathing
      (1.3% vs. 7.5%). No significant relationships were observed relative to patient
      age, gender or malocclusion. The anticipated satisfaction levels were generally
      high (86.5% vs. 89.9%). CONCLUSION: Although the distribution of motivational
      factors varied between the two sites, it did not affect the anticipated
      satisfaction level. Patients were generally confident that they would be
      satisfied with their treatment outcome and that their reasons for seeking
      treatment would be addressed.

PMID- 28438396
TI  - The versatile use of revisited de-epithelialization concept in superficial
      circumflex iliac and anterolateral thigh perforator free flap for head and neck
      reconstructions.
AB  - BACKGROUND: Although the perforator free flap is now a standard choice for head
      and neck reconstruction, problems such as microvascular complications,
      insufficient volume support for the defect, and fistula formation occur. We
      revisited a de-epithelialized concept for superficial circumflex iliac artery and
      anterolateral thigh perforator free flap to overcome these problems. METHODS: We
      applied the de-epithelized perforator free flaps in 35 cases among 761
      microsurgical head and neck reconstructions and investigated flap characteristics
      (length gain of pedicle, flap size, and volumetric analysis) and outcomes (flap
      failure, partial flap necrosis, hematoma, infection, and fistula). RESULTS:
      Satisfactory results were achieved regarding flap survival, volumetric
      compensation, and fistula formation. Flaps were transferred successfully in all
      patients, although 1 patient underwent revisional operation due to venous
      congestion. Transferred flap volume was significantly higher than the resected
      tumor volume (p < 0.01), which suggests volume augmentation in the destroyed neck
      envelope and a protective role against adjuvant radiation. Minor dehiscence and
      bleeding were seen in two cases, and no other complications were identified.
      CONCLUSION: The de-epithelialization concept for perforator free flap is helpful
      to overcome obstacles related to traditional free flaps in terms of flap survival
      and volumetric augmentation in head and neck reconstructions.

PMID- 28438397
TI  - Endothelial-to-mesenchymal transition: A novel therapeutic target for
      cardiovascular diseases.
AB  - Endothelial-to-mesenchymal transition (EndMT) is a complex biological process in
      which endothelial cells lose their specific markers and acquire a mesenchymal or
      myofibroblastic phenotype. Similar to epithelial-to-mesenchymal transition (EMT),
      EndMT can be induced by multiple stimulants such as cytokines and metabolic
      factors that play crucial roles in the development of the cardiovascular system.
      Recent studies have demonstrated that EndMT may play a significant role in the
      pathogenesis of cardiovascular diseases (CVDs), and may represent a novel
      therapeutic target for cardiovascular remodeling and fibrotic disorders. The
      exact molecular mechanisms involved in cardiovascular pathogenesis that occur as
      a result of EndMT, however, are not fully explained. In this review, we reveal
      the multiple intercellular mechanisms of EndMT including stimulants, signaling
      pathways, and seek to explore the relationship between this biological process,
      cardiovascular system development, and CVDs that may lead to new therapeutic
      strategies for the treatment of CVDs.

PMID- 28438398
TI  - Triglycerides: A reappraisal.
AB  - Elevated cholesterol levels are clearly independently associated with adverse
      cardiovascular events. Another class of lipid particles, triglycerides, is also
      abundant in the human body and has been found in atherosclerotic plaques. Recent
      observational studies have demonstrated an association between elevated
      triglyceride levels and increased risk for future cardiovascular events. With
      this knowledge and the discovery of effective agents to lower triglyceride
      levels, the management of triglycerides is currently undergoing a renaissance.
      Unfortunately, no randomized, controlled clinical trials have been completed to
      date, proving that lowering triglycerides will reduce cardiovascular events. In
      this review we highlight some of the evidence that led to this stage and discuss
      the current data on pharmacologic intervention of triglyceride levels and the
      effect on clinical outcomes. Lastly, we want to give the reader insight on what
      the most recent lipid guidelines state about clinical triglyceride management,
      mention new pharmacological agents, and highlight the clinical evidence for safe
      and effective lowering of triglycerides levels with life style modification.

PMID- 28438399
TI  - Type 2 myocardial infarction due to supply-demand mismatch.
AB  - The best-accepted definition of myocardial infarction (MI) is provided by
      statements from the Universal Definition of MI Global Task force. This article,
      now in its third iteration, defines MI as myocardial cell death due to prolonged
      myocardial ischemia. It further delineates an increasingly incident
      subclassification of MI known as type 2 MI (T2MI). T2MI identifies instances of
      myocardial necrosis in which an imbalance between myocardial oxygen supply and/or
      demand occurs for reasons other than atherosclerotic plaque disruption. While
      associated with considerable risk (comparable to that of type 1 MI, which has
      well-defined management strategies), the spectrum of potential etiologies for
      T2MI makes development of precise diagnostic criteria and therapeutic
      implications of the diagnosis challenging.

PMID- 28438400
TI  - Editor's Choice - Arteriotomy Closure Devices in EVAR, TEVAR, and TAVR: A
      Systematic Review and Meta-analysis of Randomised Clinical Trials and Cohort
      Studies.
AB  - OBJECTIVES: Cardiac and vascular surgery benefit from percutaneous interventions.
      Arteriotomy closure devices (ACDs) enable minimally invasive access to the common
      femoral artery (CFA). The objective of this review was to assess the differences
      between ACDs and surgical cut down (SCD) of the CFA regarding the number of
      complications, duration of surgery (DOS), and hospital length of stay (HLOS).
      DESIGN: A systematic literature search with predefined search terms was performed
      using MEDLINE, Embase, and the Cochrane Library (2000-2016). All studies
      reporting on ACD and SCD for a puncture of the CFA of at least 12 French (Fr.)
      were assessed for eligibility. METHODS: Included were randomised controlled
      trials and cohort studies comparing both techniques. Patient characteristics,
      exclusion criteria, and conversion rates were evaluated. Complications, DOS, and
      HLOS were compared. MATERIALS: A total of 17 studies were included for meta
      analysis, describing 7889 vascular access sites; four studies were randomised
      trials, two studies reported from a prospective database, and 11 studies reported
      retrospective cohorts. RESULTS: ACD was associated with fewer post-operative
      seromas (odds ratio [OR] 0.15, 95% confidence interval [CI] 0.06-0.35), less
      wound dehiscence (OR 0.14, 95% CI 0.03-0.78), and fewer surgical site infections
      (OR 0.38, 95% CI 0.23-0.63). Post-operative pseudoaneurysms were significantly
      more common in the ACD group (OR 3.83, 95% CI 1.55-9.44). In five of 17 studies,
      DOS and HLOS were not reduced in the ACD group. When all studies reporting a mean
      DOS and/or HLOS were compared in a non-parametric analysis, neither was
      significantly different. CONCLUSION: This meta-analysis favours ACD regarding the
      number of wound complications compared with SCD in endovascular aneurysm repair,
      thoracic endovascular aneurysm repair, and transcatheter aortic valve repair.
      Treatment duration (DOS and HLOS) was not reduced in ACD. The differences are of
      limited clinical significance and with this equivocal quality of evidence, the
      ACD may be considered safe for CFA access in suitable patients.

PMID- 28438401
TI  - A control system for ultrasound devices utilized for inactivating E. coli in
      wastewater.
AB  - Sonochemical processes applied to wastewater treatment have an influence on the
      behavior of ultrasonic systems. This is especially due to the load characteristic
      of the sonochemical process itself and the temperature increase caused by
      internal damping within the converter. Hence, a controlling device is needed to
      guarantee the operation in resonance and to keep the vibration amplitude
      constant. This paper presents a digital control system for the operation of weak
      to strong damped ultrasonic devices and its application for inactivating
      Escherichia coli in wastewater. In an experimental investigation, the electric
      data during a sonochemical process to inactivate E. coli in wastewater is taken
      into account to analyze the efficacy of the treatment process and the reaction of
      the vibration system to the process. Frequency response measurements depict that
      the resonance frequency changes with the sonicated medium and the vibration
      amplitude decreases with driving current. In addition to a common continuous
      operation of the system, different pulsed modes are investigated. The experiments
      prove the common dependencies between inactivation and power level or treatment
      time. Additionally, it is pointed out that the control of the sonochemical device
      is of utmost importance to guarantee an efficient treatment of water, because
      fast process changes, especially in pulsed operation modes, need to be controlled
      to a steady state as fast as possible. Although a water treatment efficiency
      increase using pulsed modes was not proved, it is shown, that the performance of
      the control unit is capable of using different driving modes in water treatment.

PMID- 28438402
TI  - Effects of ultrasonic and hydrodynamic cavitation on the treatment of cork
      wastewater by flocculation and Fenton processes.
AB  - This paper reports that ultrasonic (US) and hydrodynamic cavitation (HC) are
      efficient strategies for the environmental remediation of cork wastewater (CW).
      It is necessary to remove toxic, inhibitory or refractory organic matter from CW
      using physical and chemical techniques (pre-treatment) prior to performing
      conventional biological treatment. After this biological treatment, it is also
      critical to further decontaminate (post-treatment) in order to meet the discharge
      limitation. The pre-treatment of diluted CW using Fenton oxidation (FE) alone led
      to COD and polyphenol (PP) removal values of 30% and 61%, respectively, while HC
      and US resulted in 83-90% increases in COD reduction and 26-33% increases in PP
      reduction. Whereas 55% and 91% COD and PP removal were achieved using
      flocculation (Floc) alone, COD elimination was increased by a further 7-18% under
      HC and US. No noticeable improvement in PP elimination was observed. US did not
      enhance the Floc decontamination of the original concentrated CW, however,
      considerable quantities of white biofilm were surprisingly generated on the CW
      surface after the pre-treatment, thus indicating the improvement of
      biodegradability of the resulting liquid. In fact, the post-treatment stage,
      using FE alone after having filtered the biofilms, led to reductions of 53% in
      COD and 90% in PP. The HC and US protocols resulted in 26-34% increases in COD
      elimination. HC further enhanced PP elimination caused by FE, while US resulted
      in lower levels of PP elimination.

PMID- 28438403
TI  - Editorial Comment.

PMID- 28438404
TI  - Quantitative Ultrasound and Tibial Dysplasia in Neurofibromatosis Type 1.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder associated
      with unilateral anterolateral bowing with subsequent fracture and nonunion. In
      infancy, physiologic bowing of the lower leg can be confused with pathologic
      tibial dysplasia in NF1. Little is known about the bone physiology of the tibiae
      prior to fracture or predictors of fracture. The aim of this study was to
      characterize bone quality of bowed tibiae prior to fracture in NF1 using
      quantitative ultrasound (QUS). Bone quality was assessed on both tibiae (the non
      bowed and bowed tibiae) using QUS to measure speed of sound (SOS) at the mid
      shaft in 23 individuals with NF1. SOS (m/s) was determined and Z-scores generated
      using cross-sectional reference data of the same sex and age. The mean difference
      in SOS Z-scores when comparing the bowed tibia vs the individual's contralateral
      unaffected tibia was statistically significant with lower mean Z-scores in the
      bowed tibia (p = 0.001). Radiographs of all individuals with a clinical diagnosis
      of anterolateral bowing were reviewed, and in 2 individuals the radiographs
      showed minimal bowing with absence of characteristic cortical thickening and
      medullary canal narrowing in NF1-related tibial dysplasia, suggesting physiologic
      bowing. In both individuals, the Z-scores of the bowed leg were not lower than
      the unaffected leg supporting the suggestion of physiologic bowing rather than
      pathologic tibial dysplasia. These data show that dysplastic tibiae in NF1 prior
      to fracture and nonunion have abnormal bone quality with significant decreases in
      SOS even though radiographically the tibiae show a thickened cortex. These data
      also suggest that QUS can help distinguish dysplastic bowing vs physiologic
      bowing in infancy in NF1. QUS is an effective quantitative outcome measure for
      trials aimed at improving tibial bowing to prevent fracture, and it is a
      potential aid in diagnosis and clinical management in NF1.

PMID- 28438405
TI  - Myelopathy secondary to copper deficiency: The great imitator.

PMID- 28438406
TI  - Coverage and determinants of childhood immunization in Nigeria: A systematic
      review and meta-analysis.
AB  - INTRODUCTION: The proportion of fully immunized children in Nigeria is reportedly
      low. There are concerns over national immunization data quality, with this
      possibly limiting country-wide response. We reviewed publicly available evidence
      on routine immunization across Nigeria to estimate national and zonal coverage of
      childhood immunization and associated determinants. METHODS: A systematic search
      of Medline, EMBASE, Global Health and African Journals Online (AJOL) was
      conducted. We included population-based studies on childhood immunization in
      Nigeria. A random effects meta-analysis was conducted on extracted crude rates to
      arrive at national and zonal pooled estimates for the country. RESULTS: Our
      search returned 646 hits. 21 studies covering 25 sites and 26,960 children were
      selected. The estimated proportion of fully immunized children in Nigeria was
      34.4% (95% confidence interval [CI]: 27.0-41.9), with South-south zone having the
      highest at 51.5% (95% CI: 20.5-82.6), and North-west the lowest at 9.5% (95% CI:
      4.6-14.4). Mother's social engagements (OR=4.0, 95% CI: 1.9-8.1) and vaccines
      unavailability (OR=3.9, 95% CI: 1.2-12.3) were mostly reported for low coverage.
      Other leading determinants were vaccine safety concerns (OR=3.0, 95% CI: 0.9
      9.4), mother's low education (OR=2.5, 95% CI: 1.8-3.6) and poor information
      (OR=2.0, 95% CI: 0.8-4.7). CONCLUSION: Our study suggests a low coverage of
      childhood immunization in Nigeria. Due to the paucity of data in the Northern
      states, we are still uncertain of the quality of evidence presented. It is hoped
      that this study will prompt the needed research, public health and policy changes
      toward increased evenly-spread coverage of childhood immunization in the country.

PMID- 28438407
TI  - Seroprevalence of antibodies against serogroup C meningococci in the region of
      Valencia, Spain: Impact of meningococcal C conjugate vaccination.
AB  - BACKGROUND AND AIMS: Meningococcal C conjugate (MCC) vaccination programs provide
      direct and indirect protection against meningococcal disease. However, a decrease
      in the antibodies could affect herd immunity. We conducted a seroprevalence study
      to assess the immunity in subjects 8-12years after different MCCV vaccination
      programs were launched and evaluated the impact of vaccination on seroprotection.
      METHODS: Seroepidemiological study conducted from October 2010 to April 2012 in
      the region of Valencia, Spain. Sample size was not proportional to the population
      but to the expected seroprotection by age group. Sera from subjects that
      were>=3years old were tested using a standardized complement-mediated serum
      bactericidal antibodies (SBA) assay. Age-stratified proportions of subjects with
      SBA titers>=8 were considered seroprotected and evaluated. A multivariate
      logistic regression model was performed to evaluate the impact of vaccination on
      the seroprotection. RESULTS: Serum samples from 1880 subjects were collected. In
      total, 523 (27.8%) of the 1880 subjects and 446 (31.2%) of the 1430
      subjects<30years (targeted to any vaccination campaign) showed protective SBA
      titers. The highest percentage of seroprotected subjects (67.8%, 95%CI 56.9-77.4)
      was observed in those that were vaccinated in a catch-up campaign at 10-13years
      of age (20-21years old at the time of blood sampling). Those scheduled for
      immunization in infancy at 2, 4 and 6months of age (7-8years at blood sample)
      represented the lowest (7.1%, 95% CI 3.3-13.1) number of seroprotected subjects.
      Having received one vaccine dose after 12months of age was associated with
      increased seroprotection. The present study revealed a positive correlation
      between the increasing age at vaccination and longer duration of seroprotection.
      CONCLUSION: Only one in three subjects who were vaccinated with MCC vaccine was
      seroprotected after 8-12years. These findings emphasize that seroprevalence
      studies are essential to identify susceptible cohorts and to inform vaccine
      policy.

PMID- 28438408
TI  - Spray dried human and chimpanzee adenoviral-vectored vaccines are thermally
      stable and immunogenic in vivo.
AB  - Cold chain-free vaccine technologies are needed to ensure effective vaccine
      delivery and coverage, particularly in resource-poor countries. However, the
      immunogenicity and thermostability of spray dried live viral vector-based
      vaccines such as recombinant adenoviral-vectored vaccines remain to be
      investigated. To address this issue, we have spray dried human adenoviral (AdHu5)
      and chimpanzee adenoviral (AdCh68)-vectored tuberculosis vaccines in a mannitol
      and dextran matrix. Spray dried powders containing these two vaccines display the
      morphologic and chemical properties desired for long-term thermostability and
      vaccination. Upon reconstitution, they effectively transfected the cells in vitro
      with relatively small losses in viral infectivity related to the spray drying
      process. Following in vivo vaccination, AdHu5- and AdCh68-vectored vaccines were
      as immunogenic as the conventional fresh, cryopreserved liquid vaccine samples.
      Of importance, even after cold chain-free storage, at ambient temperatures and
      relatively low humidity for 30 and 90days, the vaccines retained their in vivo
      immunogenicity, while the liquid vaccine samples stored under the same conditions
      lost their immune-activating capability almost entirely. Our results support
      further development of our spray drying technologies for generating thermally
      stable adenoviral-vectored and other viral-vectored vaccines.

PMID- 28438409
TI  - Health workers' attitudes, perceptions and knowledge of influenza immunization in
      Lima, Peru: A mixed methods study.
AB  - BACKGROUND: Vaccination against seasonal influenza in health workers is
      recommended but coverage is variable. This study aimed to determine coverage of
      influenza vaccination among health workers in Lima, Peru in 2010; explore
      barriers and enabling elements for vaccination; and suggest strategies to improve
      coverage. METHODS: Qualitative interviews informed the development of a survey
      instrument that consisted of open and close-ended questions. Sub-analyses were
      done by occupational group and results were calculated as percentages for each
      possible response with confidence intervals of 95%. RESULTS: Coverage of the
      influenza vaccination was 77.2%. Vaccinated staff were less likely to have
      permanent contracts (p=0.0150) and vaccination coverage was lower in physicians
      (p=0.0001). Over 90% cited protection of themselves, families and patients as
      reasons for vaccination and 48% mentioned peer encouragement. Fear of adverse
      events (47%) and organizational barriers (>30%) were reasons for non-vaccination.
      To improve coverage, highest priority was given to strategies providing more
      information. CONCLUSIONS: Key factors in driving health worker vaccination
      include desire for protection and peer encouragement. Perceptual barriers based
      on a misunderstanding of the epidemiology of influenza and vaccination could be
      overcome by targeted education and information. Organizational barriers require
      attention to how vaccination is implemented within health facilities.

PMID- 28438410
TI  - Vaccination with recombinant Modified Vaccinia Ankara (MVA) viruses expressing
      single African horse sickness virus VP2 antigens induced cross-reactive virus
      neutralising antibodies (VNAb) in horses when administered in combination.
AB  - African horse sickness is a lethal viral disease of equids transmitted by biting
      midges of the Genus Culicoides. The disease is endemic to sub-Saharan Africa but
      outbreaks of high mortality and economic impact have occurred in the past in non
      endemic regions of Africa, Asia and Southern Europe. Vaccination is critical for
      the control of this disease but only live attenuated vaccines are currently
      available. However, there are bio-safety concerns over the use of this type of
      vaccines, especially in non-endemic countries, and live attenuated vaccines do
      not have DIVA (Differentiation of Infected from Vaccinated Animals) capacity. In
      addition, large scale manufacturing of live attenuated vaccines of AHSV
      represents a significant environmental and health risk and level 3 bio-safety
      containment facilities are required for their production. A variety of different
      technologies have been investigated over the years to develop alternative AHSV
      vaccines, including the use of viral vaccine vectors such Modified Vaccinia
      Ankara virus (MVA). In previous studies we demonstrated that recombinant MVA
      expressing outer capsid protein AHSV-VP2 induced virus neutralising antibodies
      and protection against virulent challenge both in a mouse model and in the horse.
      However, AHSV-VP2 is antigenically variable and determines the existence of 9
      different AHSV serotypes. Immunity against AHSV is serotype-specific and there is
      limited cross-reactivity between certain AHSV serotypes: 1 and 2, 3 and 7, 5 and
      8, 6 and 9. In Africa, multiple serotypes circulate simultaneously and a
      polyvalent attenuated vaccine comprising different AHSV serotypes is used. We
      investigated the potential of a polyvalent AHSV vaccination strategy based on
      combinations of MVA-VP2 viruses each expressing a single VP2 antigen from a
      specific serotype. We showed that administration of 2 different recombinant MVA
      viruses, each expressing a single VP2 protein from AHSV serotype 4 or 9, denoted
      respectively as MVA-VP2(4) and MVA-VP2(9), induced virus neutralising antibodies
      against the homologous AHSV serotypes. Vaccination was more efficient when
      vaccines were administered simultaneously than when they were administered
      sequentially. A third and fourth dose of a different MVA expressing VP2 of AHSV
      serotype 5, given 4months later to ponies previously vaccinated with MVA-VP2(4)
      and MVA-VP2(9), resulted in the induction of VNAb against serotypes 4, 5, 6, 8
      and 9. The anamnestic antibody response against AHSV 9 and AHSV 4 following the
      MVA-VP2(5) boost suggests that it is possible some shared epitopes exist between
      different serotypes. In conclusion this study showed that it is feasible to
      develop a polyvalent AHSV vaccination regime based on the use of combinations of
      MVA-VP2 viruses.

PMID- 28438411
TI  - Magnetic Resonance Imaging of the Digital Nerves of the Hand: Anatomy and
      Spectrum of Pathology.
AB  - Digital nerves are intrinsic to the sensory and motor function of the hand. These
      nerves represent the terminal ramifications of the ulnar, median, and radial
      nerves and are located distal to the carpal tunnel and Guyon canal. With magnetic
      resonance imaging, traumatic and nontraumatic abnormalities of the digital nerves
      can be shown with high contrast as well as high spatial resolution. Digital nerve
      abnormalities are most commonly posttraumatic in nature; however, infection,
      inflammatory, vascular malformations, and neoplasms can rarely occur. Magnetic
      resonance imaging is playing an increasing role in the assessment of peripheral
      nerve injury throughout the body, and in the hand, which can accurately identify
      the extent and character of digital nerve abnormalities before operative
      intervention.

PMID- 28438412
TI  - An acute intake of theobromine does not change postprandial lipid metabolism,
      whereas a high-fat meal lowers chylomicron particle number.
AB  - Postprandial responses predict cardiovascular disease risk. However, only a few
      studies have compared acute postprandial effects of a low-fat, high-carbohydrate
      (LF) meal with a high-fat, low-carbohydrate (HF) meal. Furthermore, theobromine
      has favorably affected fasting lipids, but postprandial effects are unknown.
      Because both fat and theobromine have been reported to increase fasting
      apolipoprotein A-I (apoA-I) concentrations, the main hypothesis of this
      randomized, double-blind crossover study was that acute consumption of an HF meal
      and a theobromine meal increased postprandial apoA-I concentrations, when
      compared with an LF meal. Theobromine was added to the LF meal. Nine healthy men
      completed the study. After meal intake, blood was sampled frequently for 4hours.
      Postprandial apoA-I concentrations were comparable after intake of the 3 meals.
      Apolipoprotein B48 curves, however, were significantly lower and those of
      triacylglycerol were significantly higher after HF as compared with LF
      consumption. Postprandial free fatty acid concentrations decreased less, and
      glucose and insulin concentrations increased less after HF meal consumption.
      Except for an increase in the incremental area under the curve for insulin,
      theobromine did not modify responses of the LF meal. These data show that acute
      HF and theobromine consumption does not change postprandial apoA-I
      concentrations. Furthermore, acute HF consumption had divergent effects on
      postprandial apolipoprotein B48 and triacylglycerol responses, suggesting the
      formation of less, but larger chylomicrons after HF intake. Finally, except for
      an increase in the incremental area under the curve for insulin, acute
      theobromine consumption did not modify the postprandial responses of the LF meal.

PMID- 28438414
TI  - Predictors of Trachomatous Trichiasis Surgery Outcome.
AB  - PURPOSE: Unfavorable outcomes after trachomatous trichiasis (TT) surgery are
      undermining the global trachoma elimination effort. This analysis investigates
      predictors of postoperative TT (PTT), eyelid contour abnormalities (ECAs), and
      granuloma in the 2 most common TT surgery procedures: posterior lamellar tarsal
      rotation (PLTR) and bilamellar tarsal rotation (BLTR). DESIGN: Secondary data
      analysis from a randomized, controlled, single-masked clinical trial.
      PARTICIPANTS: A total of 1000 patients with TT, with lashes touching the eye or
      evidence of epilation, in association with tarsal conjunctival scarring. METHODS:
      Participants were randomly allocated and received BLTR (n = 501) or PLTR (n =
      499) surgery. Disease severity at baseline, surgical incisions, sutures, and
      corrections were graded during and immediately after surgery. Participants were
      examined at 6 and 12 months by assessors masked to allocation. MAIN OUTCOME
      MEASURES: Predictors of PTT, ECA, and granuloma. RESULTS: Data were available for
      992 (99.2%) trial participants (496 in each arm). There was strong evidence that
      performing more peripheral dissection with scissors in PLTR (odd ratio [OR],
      0.70; 95% confidence interval [CI], 0.54-0.91; P = 0.008) and BLTR (OR, 0.83; 95%
      CI, 0.72-0.96; P = 0.01) independently protected against PTT. Baseline major
      trichiasis and mixed location lashes and immediate postoperative central
      undercorrection independently predicted PTT in both surgical procedures.
      Peripheral lashes in PLTR (OR, 5.91; 95% CI, 1.48-23.5; P = 0.01) and external
      central incision height >=4 mm in BLTR (OR, 2.89; 95% CI, 1.55-5.41; P = 0.001)
      were independently associated with PTT. Suture interval asymmetry of >2 mm (OR,
      3.18; 95% CI, 1.31-7.70; P = 0.01) in PLTR and baseline conjunctival scarring in
      BLTR (OR, 1.72; 95% CI, 1.06-2.81; P = 0.03) were independently associated with
      ECA. Older age was independently associated with ECA in both PLTR (P value for
      trend < 0.0001) and BLTR (P value for trend = 0.03). There was substantial
      intersurgeon variability in ECA rates for both PLTR (range, 19.0%-36.2%) and BLTR
      (range, 6.1%-28.7%) procedures. In PLTR surgery, irregular posterior lamellar
      incision at the center of the eyelid (OR, 6.72; 95% CI, 1.55-29.04; P = 0.01) and
      ECA (OR, 3.08; 95% CI, 1.37-6.94; P = 0.007) resulted in granuloma formation.
      CONCLUSIONS: Poor postoperative outcomes in TT surgery were associated with
      inadequate peripheral dissection, irregular incision, asymmetric suture position
      and tension, inadequate correction, and lash location. Addressing these will
      improve TT surgical outcomes.

PMID- 28438416
TI  - The epidemiology of Open Globe Injuries presenting to a tertiary referral eye
      hospital in Australia.
AB  - BACKGROUND: Open globe injuries (OGIs) account for 44% of the cost of ocular
      trauma within Australia. It is estimated that 90% of ocular trauma is
      preventable. However, there have been few epidemiological studies within
      Australia that have identified groups at risk of OGIs specifically. The aim of
      our study was to review the epidemiology of OGIs presenting to a tertiary
      referral eye hospital in Australia. METHODS: The Birmingham Eye Trauma
      Terminology (BETT) system was used to classify injuries as globe ruptures,
      penetrating eye injuries (PEIs), intraocular foreign bodies (IOFBs) or
      perforating injuries. Demographic data, past ocular history, mechanism of trauma,
      ocular injuries, and best-corrected visual acuity (BCVA) before and after
      treatment were recorded. RESULTS: The 205 OGIs included 80 globe ruptures, 71
      PEIs, 48 IOFBs and six perforating injuries. Falls predominated in older age
      groups compared to the other mechanisms of injury (p<0.0001). A fall was
      responsible for 33 globe ruptures and 82% of these had a history of previous
      intraocular surgery. Globe rupture and perforating injuries had poorer visual
      outcomes (p<0.05), consistent with previous studies. Alcohol was implicated in 20
      cases of OGI, with 11 of these due to assault. PEIs and IOFBs commonly occurred
      while working with metal. BCVA was significantly worse following removal of an
      intraocular foreign body. We found presenting BCVA to be a good predictor of BCVA
      at the time of discharge. CONCLUSIONS: The causes of OGI varied in association
      with age, with older people mostly incurring their OGI through falls and younger
      adults through assault and working with metal. Globe ruptures occurring after a
      fall often had a history of intraocular surgery. The initial BCVA is useful for
      non-ophthalmologists who are unfamiliar with the ocular trauma score to help
      predict the BCVA following treatment.

PMID- 28438413
TI  - Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the
      Modulation of Anxiety.
AB  - BACKGROUND: Increasing the available repertoire of effective treatments for mood
      and anxiety disorders represents a critical unmet need. Pharmacological
      augmentation of endogenous cannabinoid (eCB) signaling has been suggested to
      represent a novel approach to the treatment of anxiety disorders; however, the
      functional interactions between two canonical eCB pathways mediated via
      anandamide (N-arachidonylethanolamine [AEA]) and 2-arachidonoylglycerol (2-AG) in
      the regulation of anxiety are not well understood. METHODS: We utilized
      pharmacological augmentation and depletion combined with behavioral and
      electrophysiological approaches to probe the role of 2-AG signaling in the
      modulation of stress-induced anxiety and the functional redundancy between AEA
      and 2-AG signaling in the modulation of anxiety-like behaviors in mice. RESULTS:
      Selective 2-AG augmentation reduced anxiety in the light/dark box assay and
      prevented stress-induced increases in anxiety associated with limbic AEA
      deficiency. In contrast, acute 2-AG depletion increased anxiety-like behaviors,
      which was normalized by selective pharmacological augmentation of AEA signaling
      and via direct cannabinoid receptor 1 stimulation with Delta9
      tetrahydrocannabinol. Electrophysiological studies revealed 2-AG modulation of
      amygdala glutamatergic transmission as a key synaptic correlate of the anxiolytic
      effects of 2-AG augmentation. CONCLUSIONS: Although AEA and 2-AG likely subserve
      distinct physiological roles, a pharmacological and functional redundancy between
      these canonical eCB signaling pathways exists in the modulation of anxiety-like
      behaviors. These data support development of eCB-based treatment approaches for
      mood and anxiety disorders and suggest a potentially wider therapeutic overlap
      between AEA and 2-AG augmentation approaches than was previously appreciated.

PMID- 28438417
TI  - Comparing hospital outcomes between open and closed tibia fractures treated with
      intramedullary fixation.
AB  - INTRODUCTION: Tibial shaft fractures comprise a large portion of operatively
      treated long bone fractures, and present with the highest rate of open injuries.
      Intramedullary fixation has become the standard of care for both open and closed
      injuries. The rates of short term complications and hospital length of stay for
      open and closed fractures treated with intramedullary fixation is not fully
      known. Previous series on tibia fractures were performed at high volume centers,
      and data were not generalizable, further they did not report on length of stay
      and the impact of preoperative variables on infections, complications and
      reoperation. We used a large surgical database to compare these outcomes while
      adjusting for preoperative risk factors. METHODS: Data were extracted from the
      ACS-NSQIP database from 2005 to 2014. Cases were identified based on CPT codes
      for intramedullary fixation and categorized as closed vs open based on ICD9 code.
      In addition to demographic and case data, primary analysis examined correlation
      between open and closed fracture status with infection, complications,
      reoperation and hospital length of stay. Secondary analysis examined preoperative
      variables including gender, race, age, BMI, and diabetes effect on outcomes.
      RESULTS: There were 272 cases identified. There were no significant demographic
      differences between open and closed tibia fracture cases. Open fracture status
      did not increase the rate of infection, 30day complications, reoperation, or
      length of stay. The only preoperative factor that correlated with length of stay
      was age. There was no correlation between BMI, presence of insulin dependent and
      nondependent diabetes, and any outcome measure. DISCUSSION: When considering the
      complication rates for open and closed tibial shaft fractures treated with
      intramedullary fixation, there is no difference between 30-day complication rate,
      length of stay, or return to the operating room. Our reported postoperative
      infection rates were comparable to previous series, adding validity to our
      results. The heterogeneity of the hospitals included in ACS-NSQIP database allow
      our data to be generalizable. These methods may underrepresent the true
      occurrence of infection as operatively treated tibia infections may present late,
      requiring late revision. Despite limitations, the data reflect on the current
      burden of managing these once devastating injuries.

PMID- 28438415
TI  - Immediate Sequential vs. Delayed Sequential Bilateral Cataract Surgery:
      Retrospective Comparison of Postoperative Visual Outcomes.
AB  - OBJECTIVE: We conducted a retrospective comparative-effectiveness study of best
      corrected visual acuity (BCVA) and refractive error (RE) after immediate
      sequential (ISBCS) and delayed sequential (DSBCS) bilateral cataract surgery. We
      tested 2 hypotheses: (1) among DSBCS patients, second-eye outcomes were no
      different than first-eye outcomes; (2) averaged between each patient's 2 eyes,
      outcomes did not differ between ISBCS and DSBCS patients. DESIGN: Retrospective
      comparative-effectiveness study. PARTICIPANTS: Kaiser Permanente Northern
      California members who underwent noncomplex bilateral cataract surgery from
      January 1, 2013, through June 30, 2015. METHODS: We performed an intention-to
      treat analysis comparing ISBCS to DSBCS using conditional logistic regression
      analysis, accounting for surgeon and patient-level factors. MAIN OUTCOME
      MEASURES: BCVA, RE. RESULTS: The analysis of visual outcomes included both eyes
      of 13 711 DSBCS and 3561 ISBCS patients. Because of the large sample size, some
      statistical differences lacked clinical significance. Ocular comorbidities were
      slightly more prevalent in DSBCS patients. Postoperative BCVA was 20/20 or better
      in 48% of DSBCS first eyes, 49% of DSBCS second eyes, 53% of ISBCS right eyes,
      and 51% of ISBCS left eyes. The within-person difference in postoperative BCVA
      averaged zero (0.00) between the first and second DSBCS eyes, and between the
      ISBCS right and left eyes. After adjustment, average postoperative BCVA was
      better in ISBCS patients, although the difference was not statistically
      significant (compared with 20/20 or better: odds ratio for worse than 20/20 was
      0.91, 95% confidence interval 0.83-1.01). Emmetropia (spherical equivalent -0.5
      to 0 diopter) was achieved in 61% of first DSBCS eyes, 61% of second DSBCS eyes,
      63% of ISBCS right eyes, and 63% of ISBCS left eyes. After adjustment, average
      postoperative RE was no different in ISBCS compared with DSBCS patients (compared
      with emmetropia: odds ratio for ametropia was 1.02, confidence interval 0.92
      1.12). We confirmed 1 case of postoperative endophthalmitis in 10 494 ISBCS eyes
      (1.0 per 10 000 eyes) and 2 cases in 38 736 DSBCS eyes (0.5 per 10 000 eyes) (P =
      0.6), and no patient had bilateral endophthalmitis. CONCLUSIONS: Compared with
      DSBCS, we found no evidence that ISBCS was associated with worse postoperative
      BCVA or RE, or with an increased complication risk.

PMID- 28438418
TI  - Radiological evaluation of ankle arthrodesis with Ilizarov fixation compared to
      internal fixation.
AB  - INTRODUCTION: We asked whether the type of ankle joint arthrodesis stabilization
      will affect: (1) rate of union, (2) rate of adjacted-joint arthritis, (3)
      malalignment of the ankle joint. MATERIAL AND METHODS: We retrospectively
      radiological studied 62 patients who underwent ankle arthrodesis with Ilizarov
      external fixator stabilization (group 1,n=29) or internal stabilization (group
      2,n=33) from 2006 to 2015. Radiologic outcomes were mesure by: (1) rate of union,
      (2) rate of adjacent-joint arthritis, (3) malalignment of the ankle joint. The
      Levene's test,Mann-Whitney U test and Students t-test were used to the
      statistical analyses. RESULTS: Ankle fusion was achieved in 100% of patients
      treated with external fixation and in 88% with internal stabilization. Desired
      frontal plane alignment was achieved in 100% of patients with external fixation
      and 76% with internal stabilization. Desired sagittal plane alignment was
      achieved in 100% of external fixation and 85% of internal stabilization. A total
      of 14 (48.3%) patients from group 1 showed a radiographic evidence of pre
      existing adjacent-joint OA. The radiographic evidence of pre-existing adjacent
      joint OA was also found in 27(81.8%) subjects from group 2. Alterations of
      adjacent joints were also found on postoperative radiograms of 19 (65.5%)
      patients subjected to Ilizarov fixation and in all 33 patients from group 2.
      DISCUSION: Ilizarov fixation of ankle arthrodesis is associated with lower
      prevalence of adjacent-joint OA and ankle joint misalignment,and with higher
      fusion rates than after internal fixation.Although achieving a complex ankle
      fusion is generally challenging,radiological outcomes after fixation with the
      Ilizarov apparatus are better than after internal stabilization.

PMID- 28438419
TI  - Importance of extended blood group genotyping in multiply transfused patients.
AB  - Blood group antigen systems are not limited to the ABO blood groups. There is
      increasing interest in the detection of extended blood group systems on the red
      cell surface. The conventional method used to determine extended blood group
      antigens or red cell phenotype is by serological testing, which is based on the
      detection of visible haemagglutination or the presence of haemolysis. However,
      this technique has many limitations due to recent exposure to donor red cell,
      certain drugs or medications or other diseases that may alter the red cell
      membrane. We aimed to determine the red cell blood group genotype by SNP real
      time PCR and to compare the results with the conventional serological methods in
      multiply transfused patients. Sixty-three patients participated in this study
      whose peripheral blood was collected and blood group phenotype was determined by
      serological tube method while the genotype was performed using TaqMan(r) Single
      Nucleotide Polymorphism (SNP) RT-PCR assays for RHEe, RHCc, Kidd and Duffy blood
      group systems. Discrepancies were found between the phenotype and genotype
      results for all blood groups tested. Accurate red blood cell antigen profiling is
      important for patients requiring multiple transfusions. The SNP RT-PCR platform
      is a reliable alternative to the conventional method.

PMID- 28438420
TI  - Scalp-sparing total skin electron therapy in mycosis fungoides: Case report
      featuring a technique without lead.

PMID- 28438421
TI  - Community-level prejudice and mortality among immigrant groups.
AB  - This study assesses whether anti-immigrant prejudice at the community level is
      prospectively associated with mortality. We used 10 waves of data from the
      General Social Survey (GSS) that were linked to mortality data via the National
      Death Index (NDI) for the period between 1993 and 2014 (n = 13,242). The 2014 GSS
      NDI dataset is a nationally representative sample reporting social
      characteristics and attitudes in the United States that was prospectively linked
      to mortality data. Community-level prejudice was measured with 5 questions
      regarding anti-immigrant sentiments across 123 communities, defined using primary
      sampling units. Cox proportional hazards models tested the association between
      anti-immigrant prejudice and mortality hazard, controlling for covariates at the
      individual and community levels. Findings showed that among "other race"
      respondents, those born in the US had higher risk of mortality in communities
      with greater anti-immigrant prejudice, whereas foreign-born "other race"
      respondents had lower risk of mortality in communities with greater anti
      immigrant prejudice. Sensitivity analyses indicated that the "other race"
      category was comprised largely of Asians and Hispanics, and that these results
      were similar for both groups. In contrast, anti-immigrant prejudice was not
      associated with mortality for foreign-born immigrants who self-report as white or
      black. We provide various hypotheses for why US-born immigrant groups seem to
      suffer higher mortality risk, while foreign-born immigrant groups do not, when
      they live in communities with high levels of prejudice.

PMID- 28438422
TI  - Next-Generation Parasitologists: Structured Training Programs Meet Educational
      Challenges.
AB  - Parasite infections are diverse, complex and widespread, and they represent major
      health threats to people and animals alike. Topics such as vaccine development,
      drug resistance, immune regulation, vector-borne parasitic diseases, and wildlife
      parasitology are key issues. Here, we discuss the need and direction of
      structured educational programs for graduates in modern parasitology.

PMID- 28438423
TI  - Is adult congenital cardiac surgery a specialty?

PMID- 28438424
TI  - [Avascular necrosis of the capitellum humeri: A report of clinical-radiological
      case].

PMID- 28438425
TI  - Mobile laboratories: An innovative and efficient solution for radiological
      characterization of sites under or after decommissioning.
AB  - During the operation and the decommissioning of a nuclear site the operator must
      assure the protection of the workers and the environment. It must furthermore
      identify and classify the various wastes, while optimizing the associated costs.
      At all stages of the decommissioning radiological measurements are performed to
      determine the initial situation, to monitor the demolition and clean-up, and to
      verify the final situation. Radiochemical analysis is crucial for the
      radiological evaluation process to optimize the clean-up operations and to the
      respect limits defined with the authorities. Even though these types of analysis
      are omnipresent in activities such as the exploitation, the monitoring, and the
      cleaning up of nuclear plants, some nuclear sites do not have their own
      radiochemical analysis laboratory. Mobile facilities can overcome this lack when
      nuclear facilities are dismantled, when contaminated sites are cleaned-up, or in
      a post-accident situation. The current operations for the characterization of
      radiological soils of CEA nuclear facilities, lead to a large increase of
      radiochemical analysis. To manage this high throughput of samples in a timely
      manner, the CEA has developed a new mobile laboratory for the clean-up of its
      soils, called SMaRT (Shelter for Monitoring and nucleAR chemisTry). This
      laboratory is dedicated to the preparation and the radiochemical analysis (alpha,
      beta, and gamma) of potentially contaminated samples. In this framework, CEA and
      Eichrom laboratories has signed a partnership agreement to extend the analytical
      capacities and bring on site optimized and validated methods for different
      problematic. Gamma-emitting radionuclides can usually be measured in situ as
      little or no sample preparation is required. Alpha and beta-emitting
      radionuclides are a different matter. Analytical chemistry laboratory facilities
      are required. Mobile and transportable laboratories equipped with the necessary
      tools can provide all that is needed. The main advantage of a mobile laboratory
      is its portability; the shelter can be placed in the vicinity of nuclear
      facilities under decommissioning, or of contaminated sites with infrastructures
      unsuitable for the reception and treatment of radioactive samples. Radiological
      analysis can then be performed without the disadvantages of radioactive material
      transport. This paper describes how this solution allows a fast response and
      control of costs, with a high analytical capacity.

PMID- 28438426
TI  - Importance of the distinction between quality of methodology and quality of
      reporting.

PMID- 28438427
TI  - Systematic review of perioperative and survival outcomes of liver resections with
      and without preoperative portal vein embolization for colorectal metastases.
AB  - BACKGROUND: The aim of this systematic review was to evaluate perioperative and
      long term outcomes in patients who underwent PVE prior to liver resection for
      colorectal liver metastases. METHODS: A systematic search of PubMed, MEDLINE,
      Embase and the Cochrane library was performed in accordance with PRISMA
      guidelines. Studies including patients who underwent liver resection with and
      without PVE (N-PVE) were included. RESULTS: Thirteen studies including 1345 were
      included of which 539 patients had PVE and 806 had N-PVE. Eight studies reported
      that from a total of 450 patients who underwent PVE, 136 (30%) did not proceed to
      liver resection. In 114 (84%) patients this was due to disease progression. The
      postoperative morbidity was 42% (n = 151) after PVE and 10% (n = 35) developed
      postoperative liver failure after liver resection. Median overall survival,
      reported in all studies, was 38.9 months and 45.6 months respectively, following
      resection with PVE and N-PVE. The median disease free survival, reported in eight
      studies, was 15.7 (PVE) and 21.4 (N-PVE) months respectively. CONCLUSION:
      Following PVE 70% of patients proceed to liver resection, with a 10% risk of
      postoperative liver failure. Tumour progression after PVE was the predominant
      reason for not proceeding to liver resection.

PMID- 28438428
TI  - The impact of STEM aberration correction on materials science.
AB  - Over the last three decades the scanning transmission electron microscope (STEM)
      has gone from a specialized instrument for nanoscale analysis to the microscope
      of choice for atomic resolution imaging of materials, allowing incoherent high
      angle annular dark field (Z-contrast) imaging, coherent phase contrast modes
      (conventional and annular bright field), electron energy loss and energy
      dispersive X-ray spectroscopy. All signals are achieving atomic resolution and
      several are available simultaneously. This would not have been possible without
      the development of an aberration corrector for the STEM, spearheaded by Ondrej
      Krivanek in the late 1990s, which finally allowed the benefits of the STEM to
      translate from "in-principle" to actual daily practice. Here I will recall my own
      experiences with the aberration-corrected STEM in partnership with Ondrej, a
      truly exciting and rewarding journey.

PMID- 28438429
TI  - Association of serum magnesium level with poor glycemic control and renal
      functions in Nepalese patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Hypomagnesaemia has been shown to be associated with type 2 diabetes
      mellitus (T2DM) and its complications. The present study investigated the
      association of hypomagnesaemia with T2DM and its complications in patients hailed
      mostly from the western hilly region of Nepal. METHODS: This study was conducted
      among 150 type 2 diabetic patients and 150 of non-diabetic controls between May
      to September 2016. Relevant demographic, anthropometric, physiological and
      biochemical variables were measured using standard protocols. Statistical
      analyses were performed by SPSS version 17.0. RESULTS: Hypomagnesaemia (1.7+/
      0.2mg/dl) was present in 50% of diabetic patients and none in the healthy
      controls (2.0+/-0.2mg/dl). It was inversely correlated with levels of glycated
      hemoglobin (HbA1c) (r=-0.299), total cholesterol (r=-0.219), low density
      lipoprotein-cholesterol (r=-0.168) and creatinine (r=-0.215) and directly
      correlated with serum creatinine based glomerular filtration rate (eGFRcr)
      (r=0.196). Subjects with hypomagnesaemia were significantly older (57.4+/
      11.5years) and had higher levels of HbA1c (8.4+/-1.2%) and serum total
      cholesterol (248.3+/-72.0mg/dl). The methods of diabetes control did not have a
      significant influence on serum magnesium level. Patient's age (OR: 1.05 (95% CI
      1.01-1.09)), poor glycemic control (OR: 6.78 (95% CI-2.56-17.95)) and low eGFRcr
      (OR: 4.89 (95% CI-1.78-13.40)) were the significant predictors of
      hypomagnesaemia. CONCLUSION: Half of type 2 diabetic population under study had
      hypomagnesaemia without regard to the method of diabetes control. Old age, poor
      glycemic control, and low eGFRcr were the significant predictors of low serum
      magnesium in these patients. Besides their regular anti-diabetic treatment,
      clinicians should also consider dietary supplementation of magnesium to prevent
      further complications of diabetes in these patients.

PMID- 28438430
TI  - Validation of simplified Indian Diabetes Risk Score for screening undiagnosed
      diabetes in an urban setting of Haryana.
AB  - BACKGROUND AND OBJECTIVES: Identification of at risk individuals using simple
      screening tools like Indian Diabetes Risk Score (IDRS) and appropriate life style
      interventions could greatly help in preventing or delaying the onset of diabetes
      and thus reducing the burden of disease. MATERIAL AND METHOD: 450 individuals
      >20years who consented to participate were selected randomly from three
      anganwadis of urban area of Rohtak city. Demographic characteristics and
      anthropometric measurements such as weight, height and waist circumference were
      taken. BMI was calculated. IDRS developed by Mohan et al. was applied for
      categorizing the individuals as high risk, moderate risk and low risk. World
      Health Organization (WHO) criterion of fasting blood glucose >=126mg/dl was used
      for diagnosing diabetes. RESULTS: 54% of individuals were categorized as high
      risk followed by 37.6% as moderate risk as per IDRS risk score. Prevalence of
      diabetes was more in >=50years age group (28.6%) as compared to 35-49 years
      (14.2%) and 20-35 years age group (6.0%). Individuals with no physical activity
      had significantly high prevalence of diabetes as compared to mild or moderate
      physical activity (P 0.004). Similarly, males with waist circumference >=100cm
      and females with >=90cm had significantly high prevalence of diabetes (P 0.000
      and P 0.005). On multiple logistic regression analysis age, family history of
      diabetes and BMI were independent predictors of diabetes. CONCLUSION: Diabetes is
      a rising epidemic. Early screening and appropriate interventions at the start are
      needed for control of disease and risk factor modifications.

PMID- 28438431
TI  - Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy
      for early-stage glottic laryngeal cancer.
AB  - The purpose of this study was to commission and clinically test a robotic
      stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage
      glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of
      the glottic larynx onto an institutional review board (IRB)-approved clinical
      trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions
      to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid
      sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective
      hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of
      the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral
      carotid Dmax (mean 20.6 Gy reduction, p <0.001), contralateral carotid Dmax (mean
      28.1 Gy reduction, p <0.001), and thyroid Dmean (mean 15.0 Gy reduction, p
      <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose
      sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and
      spinal cord Dmax (mean 4.9 Gy reduction, p = 0.015) relative to selective
      hemilaryngeal IMRT plans. This "phantom-to-clinic" feasibility study confirmed
      that hypofractionated SBRT treatment for early-stage laryngeal cancer can
      potentially spare dose to adjacent normal tissues relative to current IMRT
      standards. Clinical efficacy and toxicity correlates continue to be collected
      through an ongoing prospective trial.

PMID- 28438432
TI  - The weight of unfinished plate: A survey based characterization of restaurant
      food waste in Chinese cities.
AB  - Consumer food waste has attracted increasing public, academic, and political
      attention in recent years, due to its adverse resource, environmental, and
      socioeconomic impacts. The scales and patterns of consumer food waste, especially
      in developing countries, however, remain poorly understood, which may hinder the
      global effort of reducing food waste. In this study, based on a direct weighing
      method and a survey of 3557 tables in 195 restaurants in four case cities, we
      investigated the amount and patterns of restaurant food waste in China in 2015.
      Food waste per capita per meal in the four cities was 93g, consisting mainly of
      vegetables (29%), rice (14%), aquatic products (11%), wheat (10%), and pork (8%).
      This equals to approximately 11kg/cap/year and is not far from that of western
      countries, although per capita GDP of China is still much lower. We found also
      that food waste per capita per meal varies considerably by cities (Chengdu and
      Lhasa higher than Shanghai and Beijing), consumer groups (tourists higher than
      local residents), restaurant categories (more waste in larger restaurants), and
      purposes of meals (friends gathering and business banquet higher than working
      meal and private dining). Our pilot study provides a first, to our best
      knowledge, empirically determined scales and patterns of restaurant food waste in
      Chinese cities, and could help set targeted interventions and benchmark national
      food waste reduction targets.

PMID- 28438433
TI  - Contribution of inhibitory receptor TIGIT to NK cell education.
AB  - Engagement of inhibitory receptors by cognate host MHC-I molecules triggers NK
      cell education, resulting in functional maturation and allowing NK cells to sense
      missing-self. However, NK cells also express inhibitory receptors for non-MHC-I
      ligands and their role in NK cell education is poorly understood. TIGIT is a
      recently identified inhibitory receptor that recognizes a non-MHC-I ligand CD155.
      Here, we demonstrated that TIGIT+ NK cells from wild-type mice exerted augmented
      responsiveness to various stimuli, including targets that lacked expression of
      CD155 ligand. TIGIT+ NK cells derived from CD155-deficient hosts, however,
      exhibited functional impairment, indicating that the engagement of TIGIT receptor
      by host CD155 promoted NK cell functional maturation. Furthermore, TIGIT
      deficiency impaired NK cell-mediated missing-self recognition and rejection of
      CD155- targets, such as allogenic splenocytes and certain tumor cells, in an MHC
      I-independent and CD226-unrelated manner. Thus, TIGIT-CD155 pathway is also
      involved in the acquisition of optimal NK cell effector function, representing a
      novel MHC-I-independent education mechanism for NK cell tolerance and activation.

PMID- 28438434
TI  - Connective tissue growth factor decreases mitochondrial metabolism through
      ubiquitin-mediated degradation of mitochondrial transcription factor A in oral
      squamous cell carcinoma.
AB  - BACKGROUND/PURPOSE: Deregulation of metabolic pathways is one of the hallmarks of
      cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor
      suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in
      modulating cancer metabolism is still unclear. METHODS: OSCC cells stably
      overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were
      established. Oxygen consumption rate (OCR) and extracellular acidification rate
      (ECAR) were examined by the Seahorse XF24 analyzer. The expression of CTGF and
      mitochondrial biogenesis related genes was measured by real-time polymerase chain
      reaction or Western blot analysis. RESULTS: CTGF decreased OCR, ECAR, adenosine
      triphosphate (ATP) generation, mitochondrial DNA (mtDNA), and mitochondrial
      transcription factor A (mtTFA) protein expression in OSCC cells. Overexpression
      of mtTFA restored CTGF-decreased OCR, ECAR, mtDNA copy number, migration and
      invasion of SAS/CTGF cells. Immunoprecipitation assay showed a higher level of
      ubiquitinated mtTFA protein after CTGF treatment. MG132, an inhibitor of
      proteasomal degradation, reversed the effect of CTGF on mtTFA protein expression
      in SAS cells. CONCLUSION: CTGF can decrease glycolysis, mitochondrial oxidative
      phosphorylation, ATP generation, and mtDNA copy number by increasing mtTFA
      protein degradation through ubiquitin proteasome pathway and in turn reduces
      migration and invasion of OSCC cells. Therefore, CTGF may be developed as a
      potential additive therapeutic drug for oral cancer in the near future.

PMID- 28438435
TI  - Postoperative treatment of metacarpal fractures-Classical physical therapy
      compared with a home exercise program.
AB  - STUDY DESIGN: Prospective cohort randomized controlled trial. PURPOSE OF THE
      STUDY: Is either a home exercise (HE) program or traditional physical therapy
      (PT) more effective in the postoperative management of metacarpal fractures?
      METHODS: Sixty patients suffering from nonthumb metacarpal fractures who received
      mobilization-stable open reduction and internal fixation were included. All
      patients were prospectively randomized into either the PT group or the HE group.
      Follow-up examinations at 2, 6 and 12 weeks postoperatively. RESULTS: After 2
      weeks, the range of motion (ROM) in both groups was still severely reduced.
      Twelve weeks after surgery the ROM improved to 245 degrees  (PT) and 256 degrees 
      (HE). Grip strength after 6 weeks was 68% (PT) and 71% (HE) when compared to the
      non-injured hand, improving to 91% (PT) and 93% (HE) after 12 weeks. CONCLUSION:
      Study results show that both HE program and traditional PT are effective in the
      postoperative management of metacarpal fractures. LEVEL OF EVIDENCE: II.

PMID- 28438437
TI  - Schizophrenia patients have higher-order language and extralinguistic
      impairments.
AB  - INTRODUCTION: The extralinguistic and paralinguistic aspects of the language
      refer to higher-order language functions such as lexical-semantic processes,
      prosody, indirect speech acts or discourse comprehension and production. Studies
      suggest that these processes are mediated by the Right Hemisphere (RH) and there
      is also some evidence of RH dysfunctions in schizophrenia. The aim of the paper
      is to investigate the extralinguistic and paralinguistic processing mediated by
      Right Hemisphere in schizophrenia patients using a validated and standardized
      battery of tests. METHODS: Two groups of participants were examined: a
      schizophrenia sample (40 participants) and a control group (39 participants).
      Extralinguistic and paralinguistic processing was assessed in all subjects by the
      Polish version of the Right Hemisphere Language Battery (RHLB-PL), which measures
      comprehension of implicit information, naming, understanding humor, inappropriate
      remarks and comments, explanation and understanding of metaphors, understanding
      emotional and language prosody and discourse understanding. RESULTS:
      Schizophrenia patients scored significantly lower than controls in subtests
      measuring comprehension of implicit information, interpretation of humor,
      explanation of metaphors, inappropriate remarks and comments, discernment of
      emotional and language prosody and comprehension of discourse. No differences
      were observed in naming, understanding metaphors or in processing visuo-spatial
      information. CONCLUSIONS: Extralinguistic and paralinguistic dysfunctions appear
      to be present in schizophrenia patients and they suggest that RH processing may
      be disturbed in that group of patients. As the disturbances of higher-order
      language processes mediated by the RH may cause serious impairments in the social
      communication of patients, it is worth evaluating them during clinical
      examination.

PMID- 28438436
TI  - Effects of dextran sulfate sodium induced experimental colitis on cytochrome P450
      activities in rat liver, kidney and intestine.
AB  - Dextran sulfate sodium (DSS) induced experimental colitis presents a histologic
      resemblance to human ulcerative colitis (UC). Altered cytochrome P450s (CYPs)
      have been reported in this model and patients with UC. In this study, six CYPs
      activities were quantitatively determined in microsomes of liver (RLMs), kidney
      (RRMs) and intestine (RIMs) from rats with colitis at acute (5% DSS for 7 days,
      UCA) and remission (7-day DSS treatment followed by 7-day cessation, UCR) phases
      and compared with normal rats. Generally, CYPs activities varied with isoform,
      organ, and disease status. Hepatic CYP1A2, 2B1, 2C6/11, 2E1 and 3A1/2 activities
      were reduced by acute colitis and completely or partially restored after DSS was
      halted. Although DSS treatment decreased the Vmax of renal CYP2C6/11 and
      increased that of CYP2D2, their CLint, in vitro were comparable among normal,
      acute and remission stages. DSS treatment changed the kinetics of CYP3A1/2
      mediated nifedipine metabolism in RRMs from biphasic to classical kinetics.
      Notably, CYP2D2 activity was elevated in liver and kidney in acute UC, while
      enhanced in liver and decreased in kidney in remission. In intestine, CYP3A1/2
      activity was increased in UCA and further enhanced after DSS withdrawal. These
      findings highlight the necessity of quantifying enzyme activity for precision
      drug therapy.

PMID- 28438438
TI  - [Multiple cephalic deep granuloma annulare of children].
AB  - BACKGROUND: Deep granuloma annulare is a fairly rare variety of granuloma
      annulare. It is seen predominantly in children and mainly affects the anterior
      aspect of the legs and the top of the feet; cephalic presentation is rare. Below,
      we report three cases of deep granuloma annulare in children presenting solely at
      the cephalic extremity. PATIENTS AND METHODS: Case 1: a six-year-old boy
      presented 7 cutaneous nodules measuring 1 to 2cm that were flesh-coloured,
      insensitive to palpation, of hard consistency and deeply attached. The lesions
      were grouped together on the anterior half of the left temporal fossa. While
      spontaneous regression of the three nodules was noted in the month following
      cutaneous biopsy, these nodules recurred a few months later. Case 2: a four-year
      old girl with five deep cephalic nodules measuring around one centimetre and the
      colour of normal skin were seen on her right temporal fossa. The child was lost
      to follow-up after biopsy. Case 3: a four-month-old infant was presenting some 15
      deep cutaneous nodules arranged in linear fashion on the forehead next to the
      left temporal fossa. These nodules regressed spontaneously one month after
      biopsy. In all three cases, histological examination confirmed the diagnosis of
      deep granuloma annulare. DISCUSSION: There have been few published cases of
      multiple, cephalic, deep granuloma annulare at a single site in children. The
      condition has an extensive differential diagnosis that includes malignant
      tumours; in addition, histological confirmation is normally essential. Treatment
      is not qualified and therapeutic extension with clinical monitoring alone may
      frequently be recommended.

PMID- 28438439
TI  - In-ear medical devices for acoustic therapies in tinnitus treatments, state of
      the art.
AB  - Cochrane reviews indicate there is very limited support for all forms of sound
      therapy and cognitive behavioral therapy has the strongest support. American
      Academy of Otolaryngology (AAO) recently published some guidelines which
      recommends Cognitive Behavioral Therapy (CBT) for tinnitus intervention, and only
      indicates that sound therapy should be considered an "option" for intervention.
      Nevertheless, acoustic therapy could lead to cause changes in the tinnitus
      perception and has been appreciated by the affected people for years. In the last
      decades, the use of sound or sound enrichment has become a central part of many
      tinnitus management programs used by audiologists, whether the intention was to
      mask tinnitus, suppress tinnitus, or interrupt the tinnitus generating neural
      activity. Several acoustic therapies have been developed and implemented in the
      last 40 years, but how can we determine which one is the most effective? We can
      determine the effects based on the results reported in many research studies, but
      in those studies are many factors that differ from one study to another, like in
      ear medical devices used to apply acoustic therapy for tinnitus treatment. In
      this article, we review and analyze the different types of in-ear medical devices
      used in the most recently acoustic therapies in treatments against tinnitus,
      allowing us to identify the pros and cons. By our analysis, an optimal medical
      device could be characterized to enhance the application of acoustic therapies
      and in consequence the global results of the sound therapies that already exist.
      In this review, it was considered acoustic therapies, the technology implemented
      in medical devices and the clinical needs.

PMID- 28438440
TI  - Pembrolizumab-induced Stevens-Johnson syndrome in non-melanoma patients.

PMID- 28438441
TI  - Topsy-turvy heart and associated imaging findings.

PMID- 28438442
TI  - Molecular identification of Enterocytozoon bieneusi and Encephalitozoon spp. in
      immunodeficient patients in Ahvaz, Southwest of Iran.
AB  - Microsporidia are often considered as an opportunistic infection in patients with
      impaired immune systems such as transplant recipients and patients with acquired
      immune deficiency syndrome (AIDS). Due to the increasing prevalence of parasitic
      infections and immunodeficiency diseases; the aim of the study is to evaluate
      molecular identification of Enterocytozoon bieneusi and Encephalitozoon spp. in
      immunodeficient patients in Ahvaz, southwest of Iran. At first, 310 stool samples
      were collected from patients with immunodeficiency. The specimens were stained by
      modified trichrome (weber) and were examined microscopically. The extracted DNA
      samples were evaluated by multiplex/nested PCR method. The products of
      multiplex/nested PCR were explored by RFLP method using the restriction enzyme of
      Mnl1. Of 310, 93 samples were suspected positive for microsporidia by the
      staining. Also, of 310, 88 samples were positive by the multiplex/nested-PCR test
      that 62 samples were positive for E. bieneusi as well as 26 were detected as
      Encephalitozoon species that including 3 E. cuniculi, 19 E. intestinalis and 4 E.
      hellem. Of 62 E. bieneusi, 45, 16 and 1 were detected as genotype D, M and WL11,
      respectively. Also, Of 3 E. cuniculi, 1 and 2 cases were identified as genotype I
      and II, respectively. All E. hellem samples were included genotype 1A. Our
      findings revealed a relatively high prevalence of microsporidia species in
      immunodeficient patients. The highest risk of this infection is at individuals
      with impaired immune systems that it can be life-threatening in people with
      immune system dysfunction. It is essential that the high-risk people should be
      receiving the information about the risk of direct contact with infected
      individuals and animals.

PMID- 28438443
TI  - Cone beam computed tomography assessment of the pterygomaxillary region and
      palatine canal for Le Fort I osteotomy.
AB  - The aim of this study was to evaluate the anatomical linear measurements of the
      descending palatine canal and the pterygomaxillary fissure for Le Fort I
      preoperative planning. Seventy-five patients, comprising 46 females (61.3%) and
      29 males (39.7%), underwent multi-slice computed tomography examinations
      performed for preoperative orthognathic surgical planning. The images were
      categorized according to sex, craniofacial side, and skeletal and craniofacial
      patterns. The anterior length between the descending palatine canal and the
      lateral wall of the piriform rim showed a higher mean value for males compared to
      females (P=0.0121). The posterior distance also showed a difference between the
      sexes and the highest mean was observed in females (P=0.0295). Comparing the
      posterior width for the skeletal patterns, a statistical difference was observed
      between classes I and III (P=0.0371), and classes II and III (P=0.0094).
      Regarding the craniofacial patterns, the brachycephalic (P=0.0078) and
      mesocephalic (P=0.0015) groups showed a greater posterior width in females. In
      conclusion, the patient's sex and aspects of the skeletal pattern and
      craniofacial pattern have an influence on the pterygomaxillary area and
      descending palatine canal anatomy. A preoperative computed tomography analysis
      involving this evaluation could reduce the risk of surgical complications.

PMID- 28438444
TI  - Review of potential drug interaction between Oseltamivir and Warfarin and why it
      is important for emergency medicine physicians.
AB  - Oseltamivir is a very commonly prescribed anti-viral medication by the Emergency
      Medicine (EM) physicians for the prophylactic and therapeutic treatment of
      Influenza infection. While the drug interaction of Warfarin with various
      antibiotics is known, the drug interaction between Oseltamivir and Warfarin is
      not common. We present a case where an 83-year female patient, on Warfarin for
      Pulmonary Embolism, had worsening of coagulopathy after she was started on
      Oseltamivir. The INR was monitored daily in our patient and Warfarin was stopped
      when the INR became supra-therapeutic. Our patient did not have any minor or
      major bleeding complication. This is the first reported case of Oseltamivir
      related worsening coagulopathy in patient on Warfarin to the best of our
      knowledge. Keeping in mind the possible interaction between the two as it was
      evident in our case and few other published reports, we recommend monitoring the
      INR closely in patients using Warfarin after they are started on Oseltamivir
      therapy.

PMID- 28438445
TI  - Minimal pneumothorax with dynamic changes in ST segment similar to myocardial
      infarction.
AB  - Pneumothorax can cause a variety of electrocardiographic changes. ST segment
      elevation, which is mainly observed in myocardial infarction, can also be induced
      by pneumothorax. The mechanism is presumed to be a decrease in cardiac output,
      due to increased intra-thoracic pressure. We encountered a patient with ST
      segment elevation with minimal pneumothorax. Coronary angiography with ergonovine
      provocation test and echocardiogram had normal findings. The ST segment elevation
      was normalized by decreasing the amount of pneumothorax. We reviewed the
      literature and present possible mechanisms for this condition.

PMID- 28438446
TI  - The association of hemodialysis and survival in intubated salicylate-poisoned
      patients.
AB  - INTRODUCTION: Salicylate poisonings are common due to their multiple uses and
      wide availability. The variation of presenting symptoms contributes to
      inconsistent treatments in the emergency department. Patients with severe
      salicylate overdose require a high minute ventilation. Early in the course of an
      overdose, a patient will require hyperventilation. If they become too fatigued to
      compensate, mechanical ventilation may be needed. It can be impossible to
      recreate such a high minute ventilation with mechanical ventilation. This places
      patients at a high risk for decompensation and death. Hemodialysis is an
      effective elimination technique for salicylate overdose and should be considered
      early. METHODS: All salicylate cases reported to the Illinois Poison Center were
      reviewed from 2003-2014. All intubated patients with a salicylate level >50mg/dl
      were included for analysis. Survival was compared to measured serum salicylate
      level and the administration of hemodialysis. RESULTS: 56 Cases were identified
      with an overall survival rate of 73.2% in patients with a serum salicylate level
      >50mg/dl. When patients did not receive hemodialysis, a peak salicylate level
      >50mg/dl had a 56% survival rate and 0% survival when the level was >80mg/dl. In
      the patients who received hemodialysis, a peak salicylate level >50mg/dl had a
      83.9% survival rate and 83.3% survival when the level was >80mg/dl. CONCLUSION:
      Survival was decreased in these patients if hemodialysis was not performed.
      Mortality increases with the measured serum salicylate level. Timely hemodialysis
      for intubated salicylate overdose patients decreases mortality.

PMID- 28438448
TI  - Should we use the Tetanus Quick Stick in the emergency department?

PMID- 28438447
TI  - Randomized clinical trial of propofol versus alfentanil for moderate procedural
      sedation in the emergency department.
AB  - STUDY OBJECTIVE: To compare the frequency of airway and respiratory adverse
      events leading to an intervention between moderate sedation using alfentanil or
      propofol. METHODS: We performed a randomized clinical trial in which adults
      undergoing moderate sedation in the ED received either alfentanil or propofol.
      Our primary outcome was the frequency of airway and respiratory adverse events
      leading to an intervention. Other outcomes included sedation depth, efficacy,
      sedation time, patient satisfaction, pain, and satisfaction. RESULTS: 108
      subjects completed the trial: 52 receiving alfentanil and 56 receiving propofol.
      Airway or respiratory adverse events leading to an intervention were similar
      between the two groups: 23% for alfentanil and 20% for propofol (p=0.657). There
      were no serious adverse events in any group. Secondary outcomes were notably
      different in the rate of reported pain (48% for alfentanil, 13% for propofol) and
      recall (75% for alfentanil, 23% for propofol) and similar in the rate of
      satisfaction with the procedure (87% for alfentanil, 84% for propofol).
      CONCLUSION: We found a similar frequency of airway and respiratory adverse events
      leading to intervention between alfentanil and propofol used for moderate
      procedural sedation. Both agents appear safe for moderate procedural sedation.

PMID- 28438449
TI  - Ankylosing Spondylitis Increases Perioperative and Postoperative Complications
      After Total Hip Arthroplasty.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic autoimmune
      spondyloarthropathy that primarily affects the axial spine and hips. Progressive
      disease leads to pronounced spinal kyphosis, positive sagittal balance, and
      altered biomechanics. The purpose of this study is to determine the complication
      profile of patients with AS undergoing total hip arthroplasty (THA). METHODS: The
      Medicare sample was searched from 2005 to 2012 yielding 1006 patients with AS who
      subsequently underwent THA. Risk ratios (RRs) with 95% confidence intervals (CIs)
      were calculated for 90-day, 2-year, and the final postoperative follow-up for
      complications including hip dislocation, periprosthetic fracture, wound
      complication, revision THA, and postoperative infection. RESULTS: Compared to
      controls, AS patients had an RR of 2.50 (CI, 1.04-5.99) of THA component breakage
      at 90-days post-operatively and 1.99 (CI, 1.10-3.59) at 2-years. The RR of
      periprosthetic hip dislocation was elevated at 90 days (1.44; CI, 0.93-2.22) and
      significantly increased at 2-years (1.67; CI, 1.25-2.23) and overall follow-up
      (1.49; CI, 1.14-1.93). Similarly, the RR for THA revision was elevated at 90-days
      (1.46; CI, 0.97-2.18) and significantly increased at 2-years (1.69; CI, 1.33
      2.14) and overall follow-up (1.51; CI, 1.23-1.85). CONCLUSION: Patients with AS
      are at increased risk for complications after THA. Altered biomechanics from a
      rigid, kyphotic spine place increased demand on the hip joints. The elevated
      perioperative and postoperative risks should be discussed preoperatively, and
      these patients may require increased preoperative medical optimization as well as
      possible changes in component selection and position to compensate for altered
      spinopelvic biomechanics.

PMID- 28438450
TI  - MONOCRYL and DERMABOND vs Staples in Total Hip Arthroplasty Performed Through a
      Lateral Skin Incision: A Randomized Controlled Trial Using a Patient-Centered
      Assessment Tool.
AB  - BACKGROUND: There are various possible methods of skin closure in total hip
      arthroplasty (THA) through a lateral skin incision. The cost and time required
      for each can vary between techniques. The objective of this study was to
      determine whether there is a difference in patient and surgeon rating of scar
      outcome using a combination of subcuticular suture and skin adhesive
      (subcuticular MONOCRYL and DERMABOND [SMD]) vs staples for skin closure after
      THA. METHODS: Patients undergoing THA were recruited from a university hospital.
      Patients were randomized to staples or SMD. Patient and Observer Scar Assessment
      Scale data were collected postoperatively. In addition, visual analog scale pain
      scores, wound drainage, length of stay, time to closure, and total cost were
      collected. RESULTS: One hundred twenty-nine patients were available for final
      analysis. There was no significant difference in Patient and Observer Scar
      Assessment Scale scores at 6 weeks or 3 months (P = .71). There was no difference
      in visual analog scale pain scores (P = .64, P = .49). The staple group had a
      higher rate of discharge on postoperative days 1 and 3 (P < .001, P < .001) but
      had a 1.6-minute shorter time of closure (P < .001). There was no significant
      difference in length of stay or total cost (P = .5). CONCLUSION: Although there
      are some small initial advantages to each method of skin closure, there is little
      difference in scar outcome when comparing SMD and staples.

PMID- 28438451
TI  - Common Medical Comorbidities Correlated With Poor Outcomes in Hip Periprosthetic
      Infection.
AB  - BACKGROUND: Periprosthetic infection has been linked to risk factors such as
      diabetes, obesity, and smoking among others. This study examined the relationship
      between common patient comorbidities and hip periprosthetic infection outcomes.
      METHODS: We retrospectively reviewed the records of 149 culture-positive
      periprosthetic hip infections at our tertiary care center that underwent
      treatment between 2005 and 2015. Baseline characteristics and common
      comorbidities were analyzed with relation to rates of successfully treated
      infection, total surgeries for infection, and cumulative length of
      hospitalization using multivariate analysis. RESULTS: Patients with coronary
      artery disease or anemia had significantly lower rate of successfully treated
      infection. Patients with anemia or chronic pulmonary disease underwent
      significantly more surgery, and patients with chronic pulmonary disease,
      psychiatric disease, anemia, or diabetes spent significantly longer time in
      hospital. CONCLUSION: Potentially modifiable cardiovascular, respiratory, and
      psychiatric diseases were associated with a decreased rate of successfully
      treated infection, more surgery, and longer hospitalization in treatment for hip
      periprosthetic infection in multivariate analysis.

PMID- 28438452
TI  - Muscle Damage After Total Hip Arthroplasty Through the Direct Anterior Approach
      for Developmental Dysplasia of the Hip.
AB  - BACKGROUND: Total hip arthroplasty (THA) through the direct anterior approach
      (DAA) is known to cause less muscle damage than other surgical approaches.
      However, more complex primary cases, such as developmental dysplasia of the hip
      (DDH), might often cause muscle damage. The objective of the present study was to
      clarify the muscle damage observed 1 year after THA through the DAA for DDH using
      magnetic resonance imaging. METHODS: We prospectively compared the muscle cross
      sectional area (M-CSA) and fatty atrophy (FA) in muscles by magnetic resonance
      imaging and the Harris hip score before and at 1-year follow-up after THA through
      the DAA in 3 groups: 37 patients with Crowe group 1 DDH (D1), 13 patients with
      Crowe group 2 and 3 DDH (D2 + 3), and 12 patients with osteonecrosis as a
      control. RESULTS: THA through the DAA for D1 displayed significantly decreased M
      CSA and significantly increased FA in the gluteus minimus (Gmini), the tensor
      fasciae latae (TFL), and the obturator internus (OI). Patients with D2 + 3 group
      did not have decreased M-CSA in the TFL or increased FA in the Gmini.
      Postoperatively, a significant negative correlation was observed between the M
      CSA and FA for the OI in patients with D1 and D2 + 3. CONCLUSION: THA through the
      DAA for DDH caused the damage in the Gmini, the TFL, and the OI; severe damage
      was observed in the OI, showing increased FA with decreased M-CSA in patients
      with both D1 and D2 + 3.

PMID- 28438454
TI  - 10-Year Follow-Up Wear Analysis of Marathon Highly Cross-Linked Polyethylene in
      Primary Total Hip Arthroplasty.
AB  - BACKGROUND: Short-term and intermediate-term wear rates for highly cross-linked
      polyethylene (HCLPE) liners in total hip arthroplasty (THA) are significantly
      lower than published rates for traditional polyethylene liners. The aim of this
      study was to report the longest-to-date follow-up of a specific HCLPE liner.
      METHODS: A series of 35 THAs using a specific HCLPE liner were reviewed.
      Anteroposterior radiographs were reviewed for femoral head penetration, the
      presence of femoral and/or acetabular osteolysis, long-term survival, total wear,
      and wear rates in all patients. RESULTS: The average patient age at time of
      surgery was 70 years with an average follow-up of 10 years (118 months; range,
      7.2-13.4 years). The mean wear rate in our cohort was 0.07 mm/y. Total wear was
      0.71 mm over the study period. No hips showed evidence of osteolysis in any
      zones. Survivorship at latest follow-up was 100% with all-cause revision as an
      end point. CONCLUSION: The wear rate of HCLPE liners continues to be lower than
      published wear rates for traditional polyethylene and continues to reaffirm the
      acceptably low wear rates using HCLPE acetabular liner in primary THA.

PMID- 28438453
TI  - Effect of Bundled Payments and Health Care Reform as Alternative Payment Models
      in Total Joint Arthroplasty: A Clinical Review.
AB  - BACKGROUND: In an effort to control rising healthcare costs, healthcare reforms
      have developed initiatives to evaluate the efficacy of alternative payment models
      (APMs) for Medicare reimbursements. The Center for Medicare and Medicaid Services
      Innovation Center (CMMSIC) introduced the voluntary Bundled Payments for Care
      Improvement (BPCI) model experiment as a means to curtail Medicare cost by
      allotting a fixed payment for an episode of care. The purpose of this review is
      to (1) summarize the preliminary clinical results of the BPCI and (2) discuss how
      it has led to other healthcare reforms and alternative payment models. METHODS: A
      literature search was performed using PubMed and the CMMSIC to explore different
      APMs and clinical results after implementation. All studies that were not in
      English or unrelated to the topic were excluded. RESULTS: Preliminary results of
      bundled payment models have shown reduced costs in total joint arthroplasty
      largely by reducing hospital length of stay, decreasing readmission rates, as
      well as reducing the number of patients sent to in-patient rehabilitation
      facilities. In order to refine episode of care bundles, CMMSIC has also developed
      other initiatives such as the Comprehensive Care for Joint Replacement (CJR)
      pathway and Surgical Hip and Femur Fracture (SHFFT). CONCLUSION: Despite the
      unknown future of the Affordable Care Act, BPCI, and CJR, preliminary results of
      alternative models have shown promise to reduce costs and improve quality of
      care. Moving into the future, surgeon control of the BPCI and CJR bundle should
      be investigated to further improve patient care and maximize financial
      compensation.

PMID- 28438455
TI  - Lesser Trochanter Size on Plain Anteroposterior Radiographs Correlates With
      Native Femoral Anteversion.
AB  - BACKGROUND: Assessing femoral version in orthopedic surgery is important for
      preoperative planning of total hip arthroplasty, especially for recognizing
      excessive anteversion or retroversion. The present study addressed the following:
      (1) Is the position of the lesser trochanter correlated to the femoral neck axis?
      (2) If so, may femoral version be assessed by means of plain pelvic radiographs?
      METHODS: Three-dimensional computed tomography scans of 60 patients undergoing
      minimally invasive cement-free total hip arthroplasty were retrospectively
      analyzed, particularly with regard to the relation between the femoral neck axis
      and the lesser trochanter, the femoral version, and the size of the projected
      lesser trochanter in different rotational positions. Based on linear regression,
      a biomathematical formula was developed to assess femoral anteversion on plain
      radiographs depending on the visible part of the lesser trochanter. RESULTS: The
      mean difference between the location of the lesser trochanter axis and the
      femoral neck axis was 43.3 degrees  +/- 6.2 degrees . Eighty-seven percent of
      patients (52 of 60) had a deviation of <10 degrees  from the mean value of 43.3
      degrees . By virtual rotation of the femur in steps of 10 degrees , the visible
      part of the lesser trochanter linearly increased with anteversion of the femur:
      femoral version = (lesser trochanter size - 5.57) * 4.17. There was a high
      correlation between the visible part of the lesser trochanter and femoral version
      (R2 = 0.75; P < .001). The lesser trochanter was no longer visible with femoral
      retroversion in each of the 60 data sets. CONCLUSION: The projected size of the
      lesser trochanter as available on plain pelvic AP radiographs correlates with
      native femoral anteversion.

PMID- 28438456
TI  - PirAB protein from Xenorhabdus nematophila HB310 exhibits a binary toxin with
      insecticidal activity and cytotoxicity in Galleria mellonella.
AB  - PirAB (Photorhabdus insect-related proteins, PirAB) toxin was initially found in
      the Photorhabdus luminescens TT01 strain and has been shown to be a binary toxin
      with high insecticidal activity. Based on GenBank data, this gene was also found
      in the Xenorhabdus nematophila genome sequence. The predicted amino acid sequence
      of pirA and pirB in the genome of X. nematophila showed 51% and 50% identity with
      those gene sequences from P. luminescens. The purpose of this experiment is to
      identify the relevant information for this toxin gene in X. nematophila. The
      pirA, pirB and pirAB genes of X. nematophila HB310 were cloned and expressed in
      Escherichia coli BL21 (DE3) using the pET-28a vector. A PirAB-fusion protein
      (PirAB-F) was constructed by linking the pirA and pirB genes with the flexible
      linker (Gly)4 DNA encoding sequence and then efficiently expressed in E. coli.
      The hemocoel and oral insecticidal activities of the recombinant proteins were
      analyzed against the larvae of Galleria mellonella. The results show that PirA/B
      alone, PirA/B mixture, co-expressed PirAB protein, and PirAB-F all had no oral
      insecticidal activity against the second-instar larvae of G. mellonella. Only
      PirA/B mixture and co-expressed PirAB protein had hemocoel insecticidal activity
      against G. mellonella fifth-instar larvae, with an LD50 of 2.718MUg/larva or
      1.566MUg/larva, respectively. Therefore, we confirmed that PirAB protein of X.
      nematophila HB310 is a binary insecticidal toxin. The successful expression and
      purification of PirAB laid a foundation for further studies on the function,
      insecticidal mechanism and expression regulation of the binary toxin.

PMID- 28438457
TI  - [Tophaceous gout of the lumbar spine in a patient without systemic gout or
      normouricaemia].
AB  - Gout is a common metabolic disorder typically diagnosed in peripheral joints.
      Tophaceous deposits in the lumbar spine is a very rare condition with very few
      cases reported in the literature. We present a case of tophaceous gout that
      originated in the lumbar spine in a patient with normal uric acid blood levels.
      The following case report concerns a 52-year-old patient with low back pain, left
      sciatica and numbness in the left leg. Serum uric acid levels were within normal
      range. MRI and bone scan images suggested an inflammatory-infectious process
      focussed at L4. After an L4-L5 decompressive laminectomy, histological
      examination revealed tissue infiltrated with mature plasma cells with negatively
      birefringent crystals using polarised light consistent with urate deposits.

PMID- 28438458
TI  - An efficient cumate-inducible system for procyclic and bloodstream form
      Trypanosoma brucei.
AB  - In Trypanosoma brucei, the tetracycline-inducible system enables tightly
      regulated, highly-efficient expression of recombinant proteins or double-stranded
      RNA in both procyclic and bloodstream form cells, providing useful molecular
      genetic tools to study gene functions. An alternative, vanillic acid-inducible
      system is recently described for procyclic T. brucei, providing ~18-fold increase
      in GFP reporter expression upon induction (Sunter JD. Mol. Biochem. Parasitol.
      2016, 207:45-48). Here we describe a cumate-inducible system that allows
      efficient, tunable gene expression showing >300-fold increase in GFP expression
      upon induction. The cumate-inducible system can be used alone or together with
      the tetracycline-inducible system, in both procyclic and bloodstream form T.
      brucei. Efficient cumate-inducible expression is also achieved in T. brucei
      infected mice.

PMID- 28438459
TI  - International Experience in Radiology Education.

PMID- 28438460
TI  - Alternative process for quantifying Na+ and K+ electrolytes in plasma with high
      paraprotein concentration using an automated analyzer.

PMID- 28438461
TI  - Bacteremia caused by the photosynthetic environmental bacterium Rhodopseudomonas.
AB  - We report a case of persistent Rhodopseudomonas bacteremia in a patient two
      months after an allogeneic bone marrow transplant for acute myeloid leukemia. The
      bacteremia persisted until IV catheter removal. To our knowledge, this is the
      first report of Rhodopseudomonas causing infection in humans.

PMID- 28438462
TI  - Comparison of interferon-gamma release assays, QuantiFERON TB-GIT and T-Spot.TB,
      in renal transplantation.
AB  - Renal transplant recipients are at increased risk of reactivating latent
      tuberculosis infection (LTBI) and progressing to active tuberculosis (TB). This
      study was conducted in National hospital for tuberculosis and renal
      transplantation (RT) in Japan. The purpose is to compare two interferon-gamma
      release assays (IGRAs), QuantiFERON(r)-TB Gold in Tube (QFT) and T-SPOT(r).TB
      (TSPOT), in patients after renal transplantation for detecting latent TB
      infection (LTBI). Total 92 renal transplant recipients (median age 46 years,
      range 17-75) were prospectively enrolled, and QFT and TSPOT were concurrently
      examined. Total subjects were 92 patients (median age 46 years, range 17-75). The
      positive rate in QFT and TSPOT were 6.5% (95% confidence interval (CI) 3.0-13.5)
      and 2.2% (95% CI 1.0-7.6), respectively. There was a significant difference in
      IGRAs positivity (P < 0.05). The negative rate in QFT and TSPOT were 91.3% (95%
      CI 83.8-95.5) and 95.7% (95% CI 89.3-98.3), respectively. There was no
      significant difference in IGRAs negativity. No patients among either IGRAs
      negative patients developed active TB during median follow-up of 994 days.
      Neither QFT nor TSPOT reaches estimated TB infection rate in Japan, especially
      elderly recipients aged 60 year-old or more. Therefore, both IGRAs might
      underestimate LTBI owing to immune suppressive therapy and aging. Physicians for
      renal transplantation need to understand the characteristics of both IGRAs and
      pay attention to the possibility of developing active TB even in patients of
      negative IGRAs results.

PMID- 28438463
TI  - Trends of reactive hyperaemia responses to repetitive loading on skin tissue of
      rats - Implications for pressure ulcer prevention.
AB  - Tissue recovery is important in preventing tissue deterioration, which is induced
      by pressure and may lead to pressure ulcers (PU). Reactive hyperaemia (RH) is an
      indicator used to identify people at risk of PU. In this study, the effect of
      different recovery times on RH trend is investigated during repetitive loading.
      Twenty-one male Sprague-Dawley rats (seven per group), with body weight of 385
      485 g, were categorised into three groups and subjected to different recovery
      times with three repetitive loading cycles. The first, second, and third groups
      were subjected to short (3 min), moderate (10 min), and prolonged (40 min)
      recovery, respectively, while fixed loading time and pressure (10 min and 50
      mmHg, respectively). Peak hyperaemia was measured in the three cycles to
      determine trends associated with different recovery times. Three RH trends
      (increasing, decreasing, and inconsistent) were observed. As the recovery time is
      increased (3 min vs. 10 min vs. 40 min), the number of samples with increasing RH
      trend decreases (57% vs. 29% vs. 14%) and the number of samples with inconsistent
      RH trend increases (29% vs. 57% vs. 72%). All groups consists of one sample with
      decreasing RH trend (14%). Results confirm that different recovery times affect
      the RH trend during repetitive loading. The RH trend may be used to determine the
      sufficient recovery time of an individual to avoid PU development.

PMID- 28438464
TI  - Association of medial prefrontal cortex connectivity with consciousness level and
      its outcome in patients with acquired brain injury.
AB  - Medial prefrontal cortex (mPFC) is usually known for participating in virtually
      all self related processing. However, few have investigated the role of mPFC in
      modulating conscious awareness. This study aimed to depict the relationship
      between the mPFC connectivity and the severity and outcome of the disorders of
      consciousness (DOC) among patients with acquired brain injury. Thirty-four
      patients with DOC (17 in a minimally conscious state and 17 in an unresponsive
      wakefulness syndrome/vegetative state) and 11 healthy controls were recruited,
      underwent clinical assessment and resting-state functional MRI scan, and were
      further followed up to evaluate recovery outcome using the Glasgow Outcome Scale.
      The mPFC connectivity was then analyzed, by comparing DOC patients to healthy
      controls at baseline, and by comparing "recovered consciousness" and "non
      recovered consciousness" patients at follow-up, as identified by graph theory. As
      a result, enhanced mPFC connectivity against weakened posteromedial cortex
      connectivity was observed in a minimally conscious state, not in an unresponsive
      wakefulness syndrome/vegetative state. Besides, increased mPFC connectivity was
      significantly associated with consciousness recovery. In conclusion, the mPFC
      connectivity could possibly serve as a mark to track the severity and outcome of
      DOC.

PMID- 28438465
TI  - Isaacs syndrome with CASPR2 antibody: A series of three cases.
AB  - Isaacs syndrome is a form of peripheral nerve hyperexcitability, characterized by
      spontaneous muscle twitching and stiffness. Some patients are reported to be
      positive for CASPR2 antibody that may be one of the pathogenic autoantibodies in
      Isaacs syndrome. We reported a series of three patients with Isaacs syndrome,
      including their clinical features, electrophysiologic findings, laboratory
      parameters and therapeutic responses. All the three patients were positive for
      CASPR2 antibodies examined on transfected human embryonic kidney 293 cells by
      indirect immunofluorescence method. One patient had invasive thymoma. Symptomatic
      treatment was not sufficient for them, while immunotherapies including
      corticosteroids, double filtration plasmapheresis and rituximab provided
      favorable outcomes. The titers of CASPR2 antibody decreased after immune
      modulating therapy in parallel to clinical improvements in two patients.

PMID- 28438466
TI  - The effect of N-acetylcysteine (NAC) on human cognition - A systematic review.
AB  - Oxidative stress, neuroinflammation and neurogenesis are commonly implicated as
      cognitive modulators across a range of disorders. N-acetylcysteine (NAC) is a
      glutathione precursor with potent antioxidant, pro-neurogenesis and anti
      inflammatory properties and a favourable safety profile. A systematic review of
      the literature specifically examining the effect of NAC administration on human
      cognition revealed twelve suitable articles for inclusion: four examining
      Alzheimer's disease; three examining healthy participants; two examining physical
      trauma; one examining bipolar disorder, one examining schizophrenia, and one
      examining ketamine-induced psychosis. Heterogeneity of studies, insufficiently
      powered studies, infrequency of cognition as a primary outcome, heterogeneous
      methodologies, formulations, co-administered treatments, administration regimes,
      and assessment confounded the drawing of firm conclusions. The available data
      suggested statistically significant cognitive improvements following NAC
      treatment, though the paucity of NAC-specific research makes it difficult to
      determine if this effect is meaningful. While NAC may have a positive cognitive
      effect in a variety of contexts; larger, targeted studies are warranted,
      specifically evaluating its role in other clinical disorders with cognitive
      sequelae resulting from oxidative stress and neuroinflammation.

PMID- 28438467
TI  - The role of impulsivity in psychostimulant- and stress-induced dopamine release:
      Review of human imaging studies.
AB  - Drug addiction is a debilitating disorder and its pivotal problem is the high
      relapse rate. To solve this problem, the aim is to prevent people from becoming
      addicted in the first place. One of the key questions that is still unanswered is
      why some people become addicted to drugs and others, who take drugs regularly, do
      not. In recent years extensive research has been done to untangle the many
      factors involved in this disorder. Here, we review some of the factors that are
      related to dopamine, i.e., impulsivity and stress (hormones), and aim to
      integrate this into a neurobiological model. Based on this, we draw two
      conclusions: (1) in order to understand the transition from recreational drug use
      to addiction, we need to focus more on these recreational users; and (2) research
      should be aimed at finding therapies that can restore inhibitory control/frontal
      functioning and improve stress resiliency in addicts.

PMID- 28438468
TI  - Clinical results and economic considerations of 68Ga-PSMA and radiolabeled
      choline in prostate cancer.
AB  - In recent years there was an impressive improvement in the options for the
      management of patients with prostate cancer. Nuclear Medicine has significantly
      enriched its diagnostic options, both in radiopharmacy and in instrumentation, in
      order to accurately target prostatic cancer cells, thus rendering the physicians
      able to adopt the best therapeutic strategy. In the present analysis, we have
      evaluated the available published data about 68Ga-PSMA and radio-labeled choline,
      two radiopharmaceutical agents for positron emission tomography/computed
      tomography (PET/CT) examination, by reporting clinical information and
      considering data about legal, economic and organization aspects.

PMID- 28438469
TI  - Regulation of conjugative transfer of plasmids and integrative conjugative
      elements.
AB  - Horizontal gene transfer has been recognized as one of the principal contributors
      to bacterial evolution and diversification. One of the mechanisms involved in
      this process is conjugative transfer of plasmids and Integrative Conjugative
      Elements (ICEs). Plasmids and ICEs often encode traits beneficial for bacterial
      survival in specific environments, or for the establishment of symbiosis or
      pathogenesis, in addition to genes allowing conjugative transfer. In this review,
      we analyze the mechanisms that regulate the expression of conjugative transfer
      genes. For traits such as antibiotic or metal resistance, the compounds involved
      may induce conjugative transfer directly, while symbiosis and pathogenesis are
      modulated by quorum-sensing and/or signal molecules released by the host.
      However, multiple layers of regulation are usually involved in modulating
      transfer. In addition to the plasmid-encoded regulatory elements, conjugation
      seems to be regulated by what we have labeled as the "internal environment",
      defined by the interaction between the host chromosome and the plasmids or ICEs.
      Another regulatory level depends on the "external environment", which affects
      conjugative transfer due to the composition and conditions of the community.

PMID- 28438470
TI  - How inflammation underlies physical and organ function in acutely admitted older
      medical patients.
AB  - OBJECTIVES: To investigate whether systemic inflammation in acutely admitted
      older medical patients (age >65 years) is associated with physical performance
      and organ dysfunction. Organ dysfunction's association with physical performance,
      and whether these associations are mediated by systemic inflammation, was also
      investigated. METHODS: A cross-sectional study in an Emergency Department.
      Physical performance was assessed by handgrip strength and de Morton Mobility
      Index (DEMMI), and organ dysfunction by FI-OutRef, the number of standard blood
      tests outside the reference range. Systemic inflammation was assessed by suPAR,
      TNFalpha, and IL-6. Associations were investigated by regression analyses
      adjusted for age, sex, cognitive impairment, CRP, and VitalPAC Modified Early
      Warning Score. RESULTS: A total of 369 patients were evaluated. In adjusted
      analyses, suPAR and TNFalpha was associated with both physical performance
      measures (p<0.001- p=0.004), and IL-6 with handgrip strength (p=0.007). All
      inflammation biomarkers were associated with FI-OutRef (p<0.001). FI-OutRef was
      also associated with physical performance (all p<0.001); suPAR being the
      inflammatory biomarker with the highest impact when adjusting for inflammation.
      CONCLUSION: Inflammatory biomarkers are potentially feasible for systematic
      assessment of vulnerability. Moreover, suPAR may be an important mediator between
      organ dysfunction and physical performance.

PMID- 28438471
TI  - Predictors of response to treatment with actovegin for 6 months in patients with
      type 2 diabetes and symptomatic polyneuropathy.
AB  - AIMS: To evaluate two definitions of response and the predictive value of
      baseline covariates for response to actovegin treatment in type 2 diabetic
      patients with symptomatic diabetic sensorimotor polyneuropathy (DSPN). METHODS:
      Response to 6-months treatment with actovegin or placebo was defined as a
      clinically meaningful decline from baseline to 6months in (1) both Neuropathy
      Impairment Score of Lower Limbs (NIS-LL) >=2 points and Total Symptom Score (TSS)
      >50% and (2) NIS-LL >=2 points only. Nineteen baseline covariates were evaluated
      using separate logistic regression models and either both NIS-LL and TSS or NIS
      LL response definitions. RESULTS: Intention-to-treat analysis included 567
      patients. Actovegin treatment compared to placebo was associated with better odds
      of response (OR [95% CI] of 1.73 [1.21-2.48] for definition 1 and 1.94 [1.33
      2.84] for definition 2). Significant interaction with actovegin treatment was
      noted only for baseline use of angiotensin receptor blockers
      (ARBs)/angiotensinogen converting enzyme inhibitors (ACEIs), resulting in a
      reduced treatment response (P=0.03). CONCLUSIONS: Actovegin treatment was
      associated with a clinically meaningful response in neuropathic symptoms and/or
      impairments in patients with symptomatic DSPN. Since only one predictor of
      response to actovegin treatment was identified, this drug seems an appropriate
      therapy for the majority of patients with DSPN.

PMID- 28438472
TI  - Shared metabolic and immune-inflammatory, oxidative and nitrosative stress
      pathways in the metabolic syndrome and mood disorders.
AB  - This review examines the shared immune-inflammatory, oxidative and nitrosative
      stress (IO&NS) and metabolic pathways underpinning metabolic syndrome (MetS),
      bipolar disorder (BD) and major depressive disorder (MDD). Shared pathways in
      both MetS and mood disorders are low grade inflammation, including increased
      levels of pro-inflammatory cytokines and acute phase proteins, increased lipid
      peroxidation with formation of malondialdehyde and oxidized low density
      lipoprotein cholesterol (LDL-c), hypernitrosylation, lowered levels of
      antioxidants, most importantly zinc and paraoxonase (PON1), increased bacterial
      translocation (leaky gut), increased atherogenic index of plasma and Castelli
      risk indices; and reduced levels of high-density lipoprotein (HDL-c) cholesterol.
      Insulin resistance is probably not a major factor associated with mood disorders.
      Given the high levels of IO&NS and metabolic dysregulation in BD and MDD and the
      high comorbidity with the atherogenic components of the MetS, mood disorders
      should be viewed as systemic neuro-IO&NS-metabolic disorders. The IO&NS-metabolic
      biomarkers may have prognostic value and may contribute to the development of
      novel treatments targeting neuro-immune, neuro-oxidative and neuro-nitrosative
      pathways.

PMID- 28438474
TI  - Tyrosine kinase-inhibitors and heart failure risk.

PMID- 28438475
TI  - A new standard of care or just another option for patients with relapsed ovarian
      cancer?

PMID- 28438473
TI  - Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction
      in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic
      Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3
      trial.
AB  - BACKGROUND: Platinum-based chemotherapy doublets are a standard of care for women
      with ovarian cancer recurring 6 months after completion of initial therapy. In
      this study, we aimed to explore the roles of secondary surgical cytoreduction and
      bevacizumab in this population, and report the results of the bevacizumab
      component here. METHODS: The multicentre, open-label, randomised phase 3 GOG-0213
      trial was done in 67 predominantly academic centres in the USA (65 centres),
      Japan (one centre), and South Korea (one centre). Eligible patients were adult
      women (aged >=18 years) with recurrent measurable or evaluable epithelial
      ovarian, primary peritoneal, or fallopian tube cancer, and a clinical complete
      response to primary platinum-based chemotherapy, who had been disease-free for at
      least 6 months following last infused cycle of platinum. Patients were randomly
      assigned (1:1) to standard chemotherapy (six 3-weekly cycles of paclitaxel [175
      mg/m2 of body surface area] and carboplatin [area under the curve 5]) or the same
      chemotherapy regimen plus bevacizumab (15 mg/kg of bodyweight) every 3 weeks and
      continued as maintenance every 3 weeks until disease progression or unacceptable
      toxicity. Individuals who participated in both the bevacizumab objective and
      surgical objective (which is ongoing) were randomly assigned (1:1:1:1) to receive
      either of these two chemotherapy regimens with or without prior secondary
      cytoreductive surgery. Randomisation for the bevacizumab objective was stratified
      by treatment-free interval and participation in the surgical objective. The
      primary endpoint was overall survival, analysed by intention to treat. This study
      is registered with ClinicalTrials.gov, number NCT00565851. FINDINGS: Between Dec
      10, 2007, and Aug 26, 2011, 674 women were enrolled and randomly assigned to
      standard chemotherapy (n=337) or chemotherapy plus bevacizumab (n=377). Median
      follow-up at the end of the trial on Nov 5, 2014, was 49.6 months in each
      treatment group (IQR 41.5-62.2 for chemotherapy plus bevacizumab; IQR 40.8-59.3
      for chemotherapy), at which point 415 patients had died (214 in the chemotherapy
      group and 201 in the chemotherapy plus bevacizumab group). Based on pretreatment
      stratification data, median overall survival in the chemotherapy plus bevacizumab
      group was 42.2 months (95% CI 37.7-46.2) versus 37.3 months (32.6-39.7) in the
      chemotherapy group (hazard ratio [HR] 0.829; 95% CI 0.683-1.005; p=0.056). We
      identified incorrect treatment-free interval stratification data for 45 (7%)
      patients (equally balanced between treatment groups); a sensitivity analysis of
      overall survival based on the audited treatment-free interval stratification data
      gave an adjusted HR of 0.823 (95% CI 0.680-0.996; p=0.0447). In the safety
      population (all patients who initiated treatment), 317 (96%) of 325 patients in
      the chemotherapy plus bevacizumab group had at least one grade 3 or worse adverse
      event compared with 282 (86%) of 332 in the chemotherapy group; the most
      frequently reported of these in the chemotherapy plus bevacizumab group compared
      with the chemotherapy group were hypertension (39 [12%] vs two [1%]), fatigue (27
      [8%] vs eight [2%]), and proteinuria (27 [8%] vs none). Two (1%) treatment
      related deaths occurred in the chemotherapy group (infection [n=1] and
      myelodysplastic syndrome [n=1]) compared with nine (3%) in the chemotherapy plus
      bevacizumab group (infection [n=1], febrile neutropenia [n=1], myelodysplastic
      syndrome [n=1], secondary malignancy [n=1]; deaths not classified with CTCAE
      terms: disease progression [n=3], sudden death [n=1], and not specified [n=1]).
      INTERPRETATION: The addition of bevacizumab to standard chemotherapy, followed by
      maintenance therapy until progression, improved the median overall survival in
      patients with platinum-sensitive recurrent ovarian cancer. Although the intention
      to-treat analysis for overall survival was not significant, our sensitivity
      analysis based on corrected treatment-free interval stratification indicates that
      this strategy might be an important addition to the therapeutic armamentarium in
      these patients. FUNDING: National Cancer Institute and Genentech.

PMID- 28438476
TI  - Fulfilling the psychological and information need of the family members of
      critically ill patients using interactive mobile technology: A randomised
      controlled trial.
AB  - BACKGROUND: Intensive care nurses may have an important role in empowering
      families by providing psychological support and fulfilling the family's pivotal
      need for information. AIM: To determine whether 'education of families by tab'
      about the patient's condition was more associated with improved anxiety, stress,
      and depression levels than the 'education of families by routine'. RESEARCH
      DESIGN: A randomized control trial of 74 main family caregivers (intervention:
      39; control: 35). SETTING: An adult intensive care unit. MAIN OUTCOME MEASURES:
      Depression Anxiety Stress Scale, and Communication and Physical Comfort Scale.
      RESULTS: Although information need satisfaction was not significantly different
      between intervention and control groups, the former reported significantly better
      depression score on Depression Anxiety Stress Scale comparing to the control
      group (p<0.01; eta2=0.09) with a medium effect size. Reduction of anxiety in the
      intervention group were clinically significant. CONCLUSION: The results suggest
      that use of 'education of family by tab' is promising for intensive care nurses
      to provide psychological support for family members. More studies are needed to
      investigate this aspect of family care for better psychological support and
      information need satisfaction that contributes to the evidence-based practice of
      intensive care nursing.

PMID- 28438477
TI  - Apnea in the term infant.
AB  - Whereas apnea of prematurity has been well defined and its pathophysiology
      extensively studied, apnea in the term infant remains a greater challenge.
      Unfortunately, clear diagnostic criteria are lacking and pathogenesis and
      management vary widely. In this review we have arbitrarily organized the
      discussion chronologically into earlier and later postnatal periods. In the first
      days of life, presumed apnea may reflect physiologic events such as positional or
      feeding etiologies, or may be a manifestation of serious pathophysiology, such as
      a seizure disorder. Beyond the neonatal period, presumed apnea may be
      characterized as a BRUE event (brief resolved unexplained event; formerly
      referred to as ALTE: apparent life-threatening event) and most frequently a
      precipitating event cannot be identified. Medical providers are left with
      somewhat of a dilemma regarding the need to hospitalize and/or work up such
      patients.

PMID- 28438478
TI  - Acute coronary syndrome in relation to the occurrence of associated symptoms: A
      quantitative study in prehospital emergency care.
AB  - INTRODUCTION: Acute chest pain is a common symptom among prehospital emergency
      care patients. Therefore, it is crucial that ambulance nurses (ANs) have the
      ability to identify symptoms and assess patients suffering from acute coronary
      syndrome (ACS). The aim of this study is to explore the occurrence of dyspnoea
      and nausea and/or vomiting in the prehospital phase of a suspected ACS and the
      associations with patients' outcome. METHODS: This study has a quantitative
      design based on data from hospital records and from a previous interventional
      study (randomised controlled trial) including five Emergency Medical Service
      (EMS) systems in western Sweden in the years 2008-2010. RESULTS: In all, 1836
      patients were included in the interventional study. Dyspnoea was reported in 38%
      and nausea and/or vomiting in 26% of patients. The risk of death within one year
      increased with the presence of dyspnoea. The presence of nausea and/or vomiting
      increased the likelihood of a final diagnosis of acute myocardial infarction
      (AMI). CONCLUSION: This study shows that dyspnoea, nausea and/or vomiting
      increase the risk of death and serious diagnosis among ACS patients. This means
      that dyspnoea, nausea and/or vomiting should influence the ANs' assessment and
      that special education in cardiovascular nursing is required.

PMID- 28438479
TI  - Family Presence During Resuscitation (FPDR): Observational case studies of
      emergency personnel in Victoria, Australia.
AB  - INTRODUCTION: Family Presence During Resuscitation (FPDR), although not a new
      concept, remains inconsistently implemented by emergency personnel. Many larger
      metropolitan emergency departments (ED) have instigated a care coordinator role,
      however these personnel are often from a non-nursing background and have
      therefore limited knowledge about the clinical aspects of the resuscitation. In
      rural emergency departments there are simply not enough staff to allocate an
      independent role. A separate care coordinator role, who is assigned to care for
      the family and not take part in the resuscitation has been well documented as
      essential to the successful implementation of FPDR. METHODS: One rural and one
      metropolitan emergency department in the state of Victoria, Australia were
      observed and data was collected on FPDR events. The participants consisted of
      resuscitation team members, including; emergency trained nurses, senior medical
      officers, general nurses and doctors. The participants were not told that the
      data would be recorded around interactions with family members or team
      discussions regarding family involvement in the resuscitation, following ethical
      approval involving limited disclosure of the aims of the study. RESULTS:
      Seventeen adult presentations (Metro n=9, Rural n=8) were included in this study
      and will be presented as resuscitation case studies. The key themes identified
      included ambiguity around resuscitation status, keeping the family informed,
      family isolation and inter-professional communication. CONCLUSION: During 17
      adult resuscitation cases, staff were witnessed communicating with family, which
      was often limited and isolation resulted. Family were often uninformed or
      separated from their family member, however when a family liaison person was
      available it was found to be beneficial. This research indicated that staff could
      benefit from a designated family liaison role, formal policy and further
      education.

PMID- 28438480
TI  - Educating Emergency Department Registered Nurses (EDRNs) in screening, brief
      intervention, and referral to treatment (SBIRT): Changes in attitudes and
      knowledge over time.
AB  - Alcohol and other drug (AOD) diagnoses in the ED co-occur with injury-related
      presenting conditions including: falls, motor vehicle accidents, poisonings, and
      both intentional and unintentional injuries. Clinical attention to ED admissions
      resulting from hazardous AOD use can significantly improve patient care and
      reduce high cost utilization of ED visits and treatment. The EDRN-SBIRT project
      is designed to improve the knowledge and attitudes of ED nurses working in a
      large academic medical center to identify and address risky AOD use as it relates
      to an ED visit. ED nurses' knowledge and attitudes toward patients with AOD use
      can be improved through SBIRT education. SBIRT education can establish an
      evidence-based standard of nursing practice to improve healthcare outcomes, but
      it must be reinforced with ongoing ED review and supportive educational sessions
      until practice is firmly established.

PMID- 28438481
TI  - Genes and neural circuits for sleep of the fruit fly.
AB  - Sleep is a universal physiological state evolutionarily conserved among species,
      but the molecular basis for its regulation is still largely unknown. Due to its
      electroencephalogram criteria, sleep has long been investigated and described
      mostly in mammalian species. The fruit fly, Drosophila melanogaster, has emerged
      as a genetic model organism for studying sleep. The Drosophila sleep is
      behaviorally defined, and is tightly regulated by circadian and homeostatic
      processes, like mammals. Genetic analyses using Drosophila have successfully
      identified a number of conserved regulatory mechanisms underlying sleep between
      flies and mammals. Identification of sleep-regulating neural circuits is required
      to further elucidate these molecular mechanisms. Two major brain regions, the
      mushroom bodies and the central complex, play crucial roles in sleep regulation
      in Drosophila. Noteworthy, many detailed studies on neural circuits in these
      brain regions have clearly shown that specific small group of neurons are
      implicated in sleep homeostasis. Thus, recent progress in Drosophila sleep
      provides novel insights into understanding the molecular and neural basis of
      sleep.

PMID- 28438482
TI  - Manufacture and preparation of human placenta-derived mesenchymal stromal cells
      for local tissue delivery.
AB  - BACKGROUND: In this study we describe the development of a Current Good
      Manufacturing Practice (CGMP)-compliant process to isolate, expand and bank
      placenta-derived mesenchymal stromal cells (PMSCs) for use as stem cell therapy.
      We characterize the viability, proliferation and neuroprotective secretory
      profile of PMSCs seeded on clinical-grade porcine small intestine submucosa
      extracellular matrix (SIS-ECM; Cook Biotech). METHODS: PMSCs were isolated from
      early gestation placenta chorionic villus tissue via explant culture. Cells were
      expanded, banked and screened. Purity and expression of markers of pluripotency
      were determined using flow cytometry. Optimal loading density and viability of
      PMSCs on SIS-ECM were determined using 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell proliferation
      and fluorescent live/dead assays, respectively. Growth factors secretion was
      analyzed using enzyme-linked immunosorbent assays (ELISA). RESULTS: PMSCs were
      rapidly expanded and banked. Viable Master and Working Cell Banks were stable
      with minimal decrease in viability at 6 months. All PMSCs were sterile, free from
      Mycoplasma species, karyotypically normal and had low endotoxin levels. PMSCs
      were homogeneous by immunophenotyping and expressed little to no pluripotency
      markers. Optimal loading density on SIS-ECM was 3-5 * 105 cells/cm2, and seeded
      cells were >95% viable. Neurotrophic factor secretion was detectable from PMSCs
      seeded on plastic and SIS-ECM with variability between donor lots. DISCUSSION:
      PMSCs from early gestation placental tissues can be rapidly expanded and banked
      in stable, viable cell banks that are free from contaminating agents, genetically
      normal and pure. PMSC delivery can be accomplished by using SIS-ECM, which
      maintains cell viability and protein secretion. Future work in vivo is necessary
      to optimize cell seeding and transplantation to maximize therapeutic
      capabilities.

PMID- 28438483
TI  - What role does rheumatoid arthritis disease activity have in cardiovascular risk.
AB  - : Rheumatoid arthritis (RA) is associated with a 1.3 to 3-fold increase in
      mortality, being the major cause of death from cardiovascular complications (40%
      50%). Therefore, the initial approach should include cardiovascular risk (CVR)
      assessment using algorithms adapted for this population. Although, SCOREM is an
      important advance, there are data indicating that subclinical atherosclerosis may
      be underdiagnosed. OBJECTIVE: To estimate the strength of association between
      carotid ultrasound and SCOREM in this population, as well as the implication of
      disease activity. METHODOLOGY: Cross-sectional, observational, analytical study
      performed at the General Hospital of Ciudad Real, Spain, between June 2013 and
      May 2014. The evaluation of CVR was performed and, according to SCOREM, the
      population was divided into low and high (medium, high and very high) risk. We
      studied the presence of subclinical atherosclerosis in low-risk patients.
      RESULTS: Of the total of 119 RA patients, 73.1% had traditional risk factors.
      Thirty-eight patients were excluded because of a previous cardiovascular event,
      diabetes mellitus and/or nephropathy. Atheromatous plaque was observed in 14.63%
      of the low-risk population. The factor with the strongest association to the
      presence of subclinical atherosclerosis was a moderate or high activity of RA
      measured by the simplified disease activity index with an odds ratio of 4.95 (95%
      CI: 1.53-16.01). CONCLUSIONS: Although there was an acceptable correlation
      between the presence of subclinical atherosclerosis and SCOREM, there was a
      considerable proportion of atheromatous plaques in low-risk patients. Disease
      activity was the risk factor most closely associated with increased CVR.

PMID- 28438484
TI  - Simultaneous object perception deficits are related to reduced visual processing
      speed in amnestic mild cognitive impairment.
AB  - Simultanagnosia, an impairment in simultaneous object perception, has been
      attributed to deficits in visual attention and, specifically, to processing
      speed. Increasing visual attention deficits manifest over the course of
      Alzheimer's disease (AD), where the first changes are present already in its
      symptomatic predementia phase: amnestic mild cognitive impairment (aMCI). In this
      study, we examined whether patients with aMCI due to AD show simultaneous object
      perception deficits and whether and how these deficits relate to visual
      attention. Sixteen AD patients with aMCI and 16 age-, gender-, and education
      matched healthy controls were assessed with a simultaneous perception task, with
      shapes presented in an adjacent, embedded, or overlapping manner, under free
      viewing without temporal constraints. We used a parametric assessment of visual
      attention based on the Theory of Visual Attention. Results show that patients
      make significantly more errors than controls when identifying overlapping shapes,
      which correlate with reduced processing speed. Our findings suggest simultaneous
      object perception deficits in very early AD, and a visual processing speed
      reduction underlying these deficits.

PMID- 28438485
TI  - Variations in the APOE allele or BDNF Val66Met polymorphism are not associated
      with changes in cognitive function following a tertiary education intervention in
      older adults: the Tasmanian Healthy Brain Project.
AB  - The apolipoprotein (APOE) epsilon4 allele and the Met variant of the brain
      derived neurotrophic factor (BDNF) Val66Met polymorphism are associated with
      reduced cognitive function in older adults. The aim of this study was to examine
      the independent and interactional effect of the APOE epsilon4 allele and BDNF
      Val66Met polymorphism on cognitive function in a cohort of healthy older adults
      who had undertaken further university level education. Multiple group latent
      growth curve modeling revealed no change in cognitive function over time in APOE
      epsilon4-carriers or in BDNF Met-carriers, nor in carriers of both APOE-epsilon4
      and BDNF-Met alleles. Further, the results indicate that allelic variation in
      either APOE or BDNF does not modify the beneficial effects of a university-based
      education intervention on cognitive function over a 4-year period following the
      intervention.

PMID- 28438486
TI  - PTI-125 binds and reverses an altered conformation of filamin A to reduce
      Alzheimer's disease pathogenesis.
AB  - We show that amyloid-beta1-42 (Abeta42) triggers a conformational change in the
      scaffolding protein filamin A (FLNA) to induce FLNA associations with alpha7
      nicotinic acetylcholine receptor (alpha7nAChR) and toll-like receptor 4 (TLR4).
      These aberrant associations respectively enable Abeta42's toxic signaling via
      alpha7nAChR to hyperphosphorylate tau protein, and TLR4 activation to release
      inflammatory cytokines. PTI-125 is a small molecule that preferentially binds
      altered FLNA and restores its native conformation, restoring receptor and
      synaptic activities and reducing its alpha7nAChR/TLR4 associations and downstream
      pathologies. Two-month oral PTI-125 administration to triple-transgenic (3xTg)
      Alzheimer's disease (AD) mice before or after apparent neuropathology and to 8
      month wildtypes with milder neuropathologies reduced receptor dysfunctions and
      improved synaptic plasticity, with some improvements in nesting behavior and
      spatial and working memory in 3xTg AD mice. PTI-125 also reduced tau
      hyperphosphorylation, aggregated Abeta42 deposition, neurofibrillary tangles, and
      neuroinflammation. Efficacy in postmortem AD and Abeta42-treated age-matched
      control hippocampal slices was concentration-dependent starting at 1 picomolar
      (pM) concentration. PTI-125 is the first therapeutic candidate to preferentially
      bind an altered protein conformation and reverse this proteopathy.

PMID- 28438487
TI  - ProcessDriver: A computational pipeline to identify copy number drivers and
      associated disrupted biological processes in cancer.
AB  - Copy number amplifications and deletions that are recurrent in cancer samples
      harbor genes that confer a fitness advantage to cancer tumor proliferation and
      survival. One important challenge in computational biology is to separate the
      causal (i.e., driver) genes from passenger genes in large, aberrated regions.
      Many previous studies focus on the genes within the aberration (i.e., cis genes),
      but do not utilize the genes that are outside of the aberrated region and
      dysregulated as a result of the aberration (i.e., trans genes). We propose a
      computational pipeline, called ProcessDriver, that prioritizes candidate drivers
      by relating cis genes to dysregulated trans genes and biological processes.
      ProcessDriver is based on the assumption that a driver cis gene should be closely
      associated with the dysregulated trans genes and biological processes, as opposed
      to previous studies that assume a driver cis gene should be the most correlated
      gene to the copy number of an aberrated region. We applied our method on breast,
      bladder and ovarian cancer data from the Cancer Genome Atlas database. Our
      results included previously known driver genes and cancer genes, as well as
      potentially novel driver genes. Additionally, many genes in the final set of
      drivers were linked to new tumor events after initial treatment using survival
      analysis. Our results highlight the importance of selecting driver genes based on
      their widespread downstream effects in trans.

PMID- 28438488
TI  - Whole genome sequencing predicts novel human disease models in rhesus macaques.
AB  - Rhesus macaques are an important pre-clinical model of human disease. To advance
      our understanding of genomic variation that may influence disease, we surveyed
      genome-wide variation in 21 rhesus macaques. We employed best-practice variant
      calling, validated with Mendelian inheritance. Next, we used alignment data from
      our cohort to detect genomic regions likely to produce inaccurate genotypes,
      potentially due to either gene duplication or structural variation between
      individuals. We generated a final dataset of >16 million high confidence
      variants, including 13 million in Chinese-origin rhesus macaques, an increasingly
      important disease model. We detected an average of 131 mutations predicted to
      severely alter protein coding per animal, and identified 45 such variants that
      coincide with known pathogenic human variants. These data suggest that expanded
      screening of existing breeding colonies will identify novel models of human
      disease, and that increased genomic characterization can help inform research
      studies in macaques.

PMID- 28438489
TI  - Laryngopharyngeal Reflux and Voice Disorders: A Multifactorial Model of Etiology
      and Pathophysiology.
AB  - OBJECTIVE: The aim of this paper is to shed light on the pathogenesis and
      pathophysiological mechanisms underlying the development of hoarseness related to
      laryngopharyngeal reflux disease (LPRD). MATERIAL AND METHODS: PubMed, Embase,
      and The Cochrane Library were searched for the terms reflux, laryngopharyngeal,
      laryngitis, voice, and hoarseness. Experimental and clinical studies providing
      substantial information about the occurrence of voice disorders, laryngeal
      histologic changes, or any pathophysiological processes related to LPRD were
      included by two independent investigators. RESULTS: Of the 104 studies reviewed,
      47 studies that met our inclusion criteria were analyzed. LPRD leads to
      significant macroscopic and microscopic histopathologic changes in the mucosa of
      the vibratory margin of the vocal folds. More and more studies suspect that
      epithelial cell dehiscence, microtraumas, inflammatory infiltrates, Reinke space
      dryness, mucosal drying, and epithelial thickening are probably responsible for
      the hoarseness related to reflux and the impairment of the subjective and
      objective voice quality evaluations. CONCLUSION: Future clinical studies
      examining the pathophysiology of hoarseness related to LPRD should take into
      consideration all potential mechanisms involved in the development of hoarseness.

PMID- 28438491
TI  - Immunomodulatory Functions of Neuronal Guidance Proteins.
AB  - Neuronal guidance proteins (NGPs) were originally identified for their role
      during the embryonic development of the nervous system. Recent years have seen
      the discovery of NGP functions during immune responses. In this context, NGPs
      were demonstrated to control leukocyte migration and the release of cytokines
      during conditions of acute inflammation, such as lung injury or sepsis. However,
      NGPs also display potent actions in the resolution of inflammation, chronic
      inflammatory conditions, the development of atherosclerosis, and during ischemia
      followed by reperfusion. Here, we provide an overview of the current state of
      knowledge about the role of NGPs in the immune system and describe their
      immunomodulatory function.

PMID- 28438490
TI  - Acute Nanoparticle Exposure to Vocal Folds: A Laboratory Study.
AB  - OBJECTIVES: Airway exposure to nanoparticles is common in occupational settings.
      Inhaled nanoparticles have toxic effects on respiratory tissue. Vocal folds are
      also at direct risk from inhaled nanoparticles. This study investigated the
      effects of single-walled carbon nanotubes (SWCNT), a type of nanoparticle, on
      vocal fold epithelium and fibroblasts. These cell types were selected for study
      as the epithelium is the outer layer of the vocal folds and fibroblasts are the
      most common cell type in connective tissue underlying the epithelium. METHODS:
      Native porcine vocal fold epithelium and cultured human vocal fold fibroblasts
      were exposed to SWCNTs (100 ng/mL) and control (no SWCNT) in vitro. Epithelial
      and fibroblast viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Epithelial barrier integrity was
      assessed with transepithelial resistance and sodium fluorescein permeability.
      Epithelial tight junctional protein occludin expression was measured with Western
      blot. Gene expressions of the fibroblast-specific protein 1 (FSP-1), alpha-smooth
      muscle actin (alpha-SMA), and collagen III (Col-III) were assessed using
      quantitative polymerase chain reaction. RESULTS: Transcriptional expression of
      genes encoding FSP-1 and Col-III was increased significantly following SWCNT
      exposure. There were no significant differences between control and SWCNT groups
      on any of the other measures. CONCLUSIONS: SWCNT exposure induces vocal fold
      fibroblasts to a fibrotic phenotype. These data help us understand vocal fold
      defense mechanisms and lay the groundwork for studying the physiological effects
      of nanoparticle exposure in vivo.

PMID- 28438492
TI  - Metabolism of 14C-octamethylcyclotetrasiloxane ([14C]D4) or 14C
      decamethylcyclopentasiloxane ([14C]D5) orally gavaged in rainbow trout
      (Oncorhynchus mykiss).
AB  - Critical factors (uptake, distribution, metabolism and elimination) for
      understanding the bioaccumulation/biomagnification potential of
      Octamethylcyclotetrasiloxane (D4) and Decamethylcyclopentasiloxane (D5) siloxanes
      in fish were investigated to address whether these chemicals meet the "B"
      criteria of the Persistent, Bioaccumulative, and Toxic (PBT) classification. A
      metabolism study was conducted in rainbow trout whereby a 15mg [14C]D4/kg bw or
      [14C]D5/kg bw as a single bolus oral dose was administered via gavage. Of the
      administered dose, 79% (D4) and 78% (D5) was recovered by the end of the study
      (96-h). Eighty-two percent and 25% of the recovered dose was absorbed based on
      the percentage of recovered dose in carcass (69% and 17%), tissues, bile and
      blood (12% and 8%) and urine (1%) for D4 and D5, respectively. A significant
      portion of the recovered dose (i.e. 18% for D4 and 75% for D5) was eliminated in
      feces. Maximum blood concentrations were 1.6 and 1.4MUg D4 or D5/g blood at 24h
      post-dosing, with elimination half-lives of 39h (D4) and 70h (D5). Modeling of
      parent and metabolite blood concentrations resulted in estimated metabolism rate
      constants (km(blood)) of 0.15 (D4) and 0.17day-1(D5). Metabolites in tissues,
      bile, blood, and urine totaled a minimum of 2% (D4) and 14% (D5) of the absorbed
      dose. The highest concentration of 14C-activity in the fish following D4
      administration was in mesenteric fat followed by bile, but the opposite was true
      for D5. Metabolites were not detected in fat, only parent chemical. In bile, 94%
      (D4) and 99% (D5) of the 14C-activity was due to metabolites. Metabolites were
      also detected in the digestive tract, liver and gonads. Approximately 40% of the
      14C-activity detected in the liver was due to the presence of metabolites.
      Urinary elimination represented a minor pathway, but all the 14C-activity in the
      urine was associated with metabolites. Clearance may occur via enterohepatic
      circulation of metabolic products in bile with excretion via the digestive tract
      and urinary clearance of polar metabolites.

PMID- 28438493
TI  - Definition determines weight regain outcomes after sleeve gastrectomy.
AB  - BACKGROUND: Sleeve gastrectomy (SG) is one of the most commonly undertaken
      bariatric procedures. Weight regain after bariatric surgery, when significant,
      may be associated with recurrence of diabetes and deterioration in quality of
      life. Furthermore, it may be more common after SG than bypass procedures. Yet the
      understanding of the significance of weight regain is hampered by poor reporting
      and no consensus statements or guidelines. OBJECTIVES: To illustrate how the lack
      of a standard definition significantly alters reported SG outcomes and to
      contribute to the discussion of how weight regain should be defined. SETTING:
      Counties Manukau Health, a public teaching hospital that performs over 150
      bariatric procedures per year. METHODS: A retrospective cohort of SG patients
      followed up at 5 years was used to illustrate how the presence of multiple
      definitions in the literature significantly affects outcome reporting for weight
      regain. Post hoc analyses were used to explore the relationship between weight
      change and clinical outcomes. RESULTS: Applying 6 definitions of weight regain to
      a retrospective cohort of SG patients resulted in 6 different rates ranging from
      9%-91%. Post hoc analyses revealed significant associations between weight change
      and the Bariatric Analysis Reporting Outcome System (BAROS) score as well as
      patient opinion. CONCLUSION: The nonuniform reporting of weight regain appears to
      significantly affect SG outcome reporting. Development of consensus statements
      and guidelines would ameliorate this problem. Ideally, research groups with
      access to large robust databases would aid in the development of any proposed
      weight regain definitions. In the interim, bariatric literature would benefit by
      all published series clearly reporting how weight regain is defined in the study
      population.

PMID- 28438494
TI  - Comparative effectiveness of sleeve gastrectomy versus Roux-en-Y gastric bypass
      for weight loss and safety outcomes in older adults.
AB  - BACKGROUND: Most bariatric studies in older adult patients have focused on older
      operations with limited follow-up and equivocal results. OBJECTIVES: To compare
      weight loss and safety in patients ages>=65 years undergoing laparoscopic sleeve
      gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). SETTING: Nine
      different bariatric surgery centers with 23 surgeons serving over 30,000
      bariatric patients. METHODS: Participants were>=65 years who had a SG or LRYGB
      between January 1, 2010, and March 15, 2015. Outcomes measured were change in
      weight up to 4 years after surgery; 30-, 90-, and 365-day mortality; and early
      (<=30 d) and late (31-365 d) complication rates. To control for nonrandom
      assignment, SG and LRYGB cases were propensity matched at the time of surgery for
      gender, race/ethnicity, procedure year, body mass index, presence of diabetes
      and/or hypertension, and overall co-morbidity burden. RESULTS: There were 177
      LRYGB and 252 SG patients (n = 429). Patients were female (70%), 67 years old
      (range 65 to 79), non-Hispanic white (64%), and had a body mass index of 42.6+/
      5.4 kg/m2. The year 4 follow-up rate was 75% (n = 322). LRYGB patients lost
      significantly more weight than SG after a median 4 years of follow-up (P<.001),
      mortality was similar, and LRYGB had higher overall complication rates (30.5%)
      than SG (15.4%). CONCLUSIONS: Elderly patients lost significantly more weight
      with LRYGB compared with SG. Further studies will be necessary to determine if
      the long-term effects of greater weight loss warrant the increased risk involved
      with LRYGB.

PMID- 28438495
TI  - Gastrointestinal symptoms after bariatric surgery-more focus needed.

PMID- 28438496
TI  - Implementing Best Practice Guidelines in Pain Assessment and Management on a
      Women's Psychiatric Inpatient Unit: Exploring Patients' Perceptions.
AB  - Assessing and managing chronic pain in women with histories of interpersonal
      trauma, mood disorders and co-morbid addiction is complex. The aim of this paper
      is to report on the findings from a quality improvement project exploring women's
      experiences who have co-occurring mental health issues, addiction and chronic
      pain. Exploring perceptions was an initial step in implementing the Registered
      Nurses' Association of Ontario (RNAO) Best Practice Guideline (BPG) on the
      Assessment and Management of Pain. Focus group discussions were conducted using
      an exploratory design with 10 women who were hospitalized in an acute psychiatric
      unit. Our findings suggest that these women view their pain as complex and often
      feel powerless within an acute psychiatric setting resorting to coping through
      self management. The women expressed the importance of therapeutic relationships
      with clinicians in assessing and managing their pain. The implications of this
      study suggest that patients have a key role in informing the implementation and
      applicability of best practice guidelines. Validating the patient's personal pain
      management experience and particular psychological and physical therapies were
      suggested as strategies to enhance the patient's quality of life. Many clinicians
      working in mental health are knowledgeable about these therapies, but may not be
      aware of the application to managing physical pain.

PMID- 28438497
TI  - Theory of Planned Behavior Constructs Associated with Nurses' Pain Assessment and
      Pro Re Nata (PRN) Opioid Analgesic Administration: A Cross-sectional Study.
AB  - Little theory-based research has been performed to better understand nurses'
      perceptions of pain management. Framed by the theory of planned behavior, the
      aims of the study were to describe nurses' beliefs (behavioral, normative, and
      control) about pain management for hospitalized elderly patients with
      postoperative pain; to present an item analysis for beliefs, attitudes, perceived
      norms, perceived behavioral control, intentions, and behaviors (measured in case
      study vignettes) for nurses (a) with different durations of nursing experience,
      (b) working in university, public health, and military hospitals, and (c) who
      either had or had not received pain management training in the past six months;
      and to compare differences in the constructs across these three groups. A
      comparative descriptive cross-sectional design was used with a convenience sample
      of 140 Thai nurses working in three Bangkok hospitals. Participants responded to
      pain assessment and management questionnaires. Most nurses expressed fairly
      strong beliefs about pain assessment and pro re nata (PRN) opioid analgesic
      administration. Nurses with more than 10 years of experience had the highest
      scores for attitudes toward pain assessment and perceptions of others'
      expectations about PRN opioid analgesic administration. Responses of nurses
      working in different types of hospitals indicated significantly different pain
      assessment and PRN opioid analgesic administration behaviors. No significant
      differences were found for nurses who did and did not receive pain management
      training. The study highlighted the need for improved pain management education
      for nurses to enhance the quality of patient care.

PMID- 28438498
TI  - Performance of MALDI-TOF MS for identification of oral Prevotella species.
AB  - During the past decade, the clinically relevant genus Prevotella has expanded
      considerably. Prevotella species can be isolated from nearly all types of oral
      infections but also from various non-oral infections. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been
      introduced in clinical microbiology laboratories as a convenient method for
      identifying bacterial isolates from clinical specimens. Here we tested the
      diagnostic accuracy of a total of 123 oral Prevotella isolates, selected based on
      their biochemical profile, by Bruker MALDI-TOF MS. Partial 16S rRNA sequencing
      was used as a reference method. The performance of MALDI-TOF MS to identify the
      isolates to the genus level was excellent with 100.0% accuracy, while a good
      identification rate of 88.6% was achieved to the species level with a log score
      of >=2.0. The isolates representing P. aurantiaca and P. jejuni, which are
      currently missing from the MALDI BioTyper database, were identified correctly to
      the genus level. Of the 123 isolates, one P. pallens isolate (0.8%) was
      identified with a score variation of 1.7-1.999. Overall, biochemical testing
      produced a high proportion (70.7%) of incorrect identifications within different
      species. MALDI-TOF MS offers a reliable and rapid method for the identification
      of Prevotella species included in the database.

PMID- 28438499
TI  - Rationalizing endpoints for prospective studies of pulmonary exacerbation
      treatment response in cystic fibrosis.
AB  - BACKGROUND: Given the variability in pulmonary exacerbation (PEx) management
      within and between Cystic Fibrosis (CF) Care Centers, it is possible that some
      approaches may be superior to others. A challenge with comparing different PEx
      management approaches is lack of a community consensus with respect to treatment
      response metrics. In this analysis, we assess the feasibility of using different
      response metrics in prospective randomized studies comparing PEx treatment
      protocols. METHODS: Response parameters were compiled from the recent STOP
      (Standardized Treatment of PEx) feasibility study. Pulmonary function responses
      (recovery of best prior 6-month and 12-month FEV1% predicted and absolute and
      relative FEV1% predicted improvement from treatment initiation) and sign and
      symptom recovery from treatment initiation (measured by the Chronic Respiratory
      Infection Symptom Score [CRISS]) were studied as categorical and continuous
      variables. The proportion of patients retreated within 30days after the end of
      initial treatment was studied as a categorical variable. Sample sizes required to
      adequately power prospective 1:1 randomized superiority and non-inferiority
      studies employing candidate endpoints were explored. RESULTS: The most sensitive
      endpoint was mean change in CRISS from treatment initiation, followed by mean
      absolute FEV1% predicted change from initiation, with the two responses only
      modestly correlated (R2=.157; P<0.0001). Recovery of previous best FEV1 was a
      problematic endpoint due to missing data and a substantial proportion of patients
      beginning PEx treatment with FEV1 exceeding their previous best measures (12.1%
      >12-month best, 19.6% >6-month best). Although mean outcome measures deteriorated
      approximately 2-weeks post-treatment follow-up, the effect was non-uniform: 62.7%
      of patients experienced an FEV1 worsening versus 49.0% who experienced a CRISS
      worsening. CONCLUSIONS: Results from randomized prospective superiority and non
      inferiority studies employing mean CRISS and FEV1 change from treatment
      initiation should prove compelling to the community. They will need to be large,
      but appear feasible.

PMID- 28438502
TI  - US drug shortages might have led to more patient deaths.

PMID- 28438501
TI  - Fatigue in COPD: an important yet ignored symptom.

PMID- 28438500
TI  - AP2 alpha modulates cystic fibrosis transmembrane conductance regulator function
      in the human intestine.
AB  - BACKGROUND: AP2 is a clathrin-based endocytic adaptor complex comprising alpha,
      beta2, MU2 and sigma2 subunits. MU2 regulates CFTR endocytosis. The alpha subunit
      interacts with CFTR in the intestine but its physiologic significance is unclear.
      METHODS: CFTR short circuit current was measured in intestinal T84 cells
      following shRNA knock down of AP2alpha (AP2alphaKD). Clathrin-coated structures
      (CCS) were immunolabeled and quantified in AP2alphaKD intestinal Caco2BBe (C2BBe)
      cells. GST tagged human AP2alpha appendage domain was cloned and its interaction
      with CFTR determined by GST pull down assay. RESULT: AP2alphaKD in T84 cells
      resulted in higher CFTR current (57%) compared to control, consistent with
      increased functional CFTR and delayed endocytosis. Depletion of AP2alpha reduced
      CCS in C2BBe cells. Pull down assays revealed an interaction between human
      AP2alpha appendage domain and CFTR. CONCLUSION: AP2 alpha interacts with and
      modulates CFTR function in the intestine by participating in clathrin assembly
      and recruitment of CFTR to CCS.

PMID- 28438503
TI  - Expanding Role of Certified Electronic Health Records Technology in Radiology:
      The MACRA Mandate.
AB  - Radiology has historically been at the forefront of innovation and the
      advancement of technology for the benefit of patient care. However, challenges to
      early implementation prevented most radiologists from adopting and integrating
      certified electronic health record technology (CEHRT) into their daily workflow
      despite the early and potential advantages it offered. This circumstance places
      radiology at a disadvantage in the two payment pathways of the Medicare Access
      and CHIP Reauthorization Act of 2015: the Merit-Based Incentive Payment System
      (MIPS) and advanced alternative payment models (APMs). Specifically, not
      integrating CEHRT hampers radiology's ability to receive bonus points in the
      quality performance category of the MIPS and in parallel threatens certain
      threshold requirements for advanced APMs under the new Quality Payment Program.
      Radiology must expand the availability and use of CEHRT to satisfy existing
      performance measures while creating new performance measures that create value
      for the health care system. In addition, radiology IT vendors will need to ensure
      their products (eg, radiology information systems, PACS, and radiology reporting
      systems) are CEHRT compliant and approved. Such collective efforts will increase
      radiologists' quality of patient care, contribution to value driven activities,
      and overall health care relevance.

PMID- 28438504
TI  - Agomelatine protects against neuronal damage without preventing epileptogenesis
      in the kainate model of temporal lobe epilepsy.
AB  - Recent studies about the novel antidepressant agomelatine, which is a mixed MT1
      and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist
      possessing an anticonvulsant and neuroprotective action, suggest that it may have
      potential to contribute against epileptogenesis and epilepsy-induced memory
      impairment. In order to ascertain whether protection of some brain structures
      could suppress epileptogenesis, in the present study, we evaluated the effect of
      chronic post-status treatment with agomelatine on epileptogenesis, behavioral and
      neuronal damage induced by kainate acid (KA) status epilepticus (SE).
      Agomelatine/vehicle treatment (40mg/kg, i.p.) started one hour after SE and
      continued up to 10weeks in Wistar rats. Latency for onset of spontaneous motor
      seizures (SMS) and their frequency was detected by a 24-h video-recording.
      Locomotor activity, anxiety and hippocampus-dependent spatial memory in open
      field (OF), elevated plus maze (EPM), light-dark test (LDT) and radial arm maze
      (RAM) test, respectively, were evaluated during the last two weeks after SE.
      Agomelatine significantly decreased the latency for onset of SMS and increased
      the seizure frequency during the 2nd and the 3rd week of treatment. The MT1 and
      MT2 receptor agonist and serotonin 5HT2C receptor antagonist exacerbated the KA
      induced hyperlocomotion and impulsive behavior and it was unable to prevent
      spatial memory impairment of epileptic rats. However, agomelatine induced a
      neuroprotection in the dorsal hippocampus, specifically in the CA1, septal CA2
      and partially in the CA3c region, the hilus of the dentate gyrus, piriform cortex
      and septo-temporal and temporal basolateral amygdala. Our findings suggest that
      the beneficial impact against SE-induced neuronal loss exerted by agomelatine is
      not crucial for the suppression of epileptogenesis and its deleterious
      consequences in KA model of temporal lobe epilepsy.

PMID- 28438506
TI  - Diacylglycerol Kinase zeta Limits Cytokine-dependent Expansion of CD8+ T Cells
      with Broad Antitumor Capacity.
AB  - Interleukin-2 and -15 drive expansion/differentiation of cytotoxic CD8+ T cells
      that eliminate targets via antigen-independent killing. This property is
      clinically relevant for the improvement of T cell-based antitumor therapies.
      Diacylglycerol kinase alpha and zeta (DGKalpha/zeta) metabolize the
      diacylglycerol generated following antigen recognition by T lymphocytes. Enhanced
      expression of these two lipid kinases in tumor-infiltrating CD8+ T cells promotes
      a hyporesponsive state that contributes to tumor immune escape. Inhibition of
      these two enzymes might thus be of interest for potentiating conventional antigen
      directed tumor elimination. In this study, we sought to characterize the
      contribution of DGKalpha and zeta to antigen-independent cytotoxic functions of
      CD8+ T cells. Analysis of DGKzeta-deficient mice showed an increase in bystander
      memory-like CD8+ T cell populations not observed in DGKalpha-deficient mice. We
      demonstrate that DGKzeta limits cytokine responses in an antigen-independent
      manner. Cytokine-specific expansion of DGKzeta-deficient CD8+ T cells promoted
      enhanced differentiation of innate-like cytotoxic cells in vitro, and correlated
      with the more potent in vivo anti-tumor responses of DGKzeta-deficient mice
      engrafted with the murine A20 lymphoma. Our studies reveal a isoform-specific
      function for DGKzeta downstream of IL-2/IL-15-mediated expansion of innate-like
      cytotoxic T cells, Pharmacological manipulation of DGKzeta activity is of
      therapeutic interest for cytokine-directed anti-tumor treatments.

PMID- 28438508
TI  - Comments on the "nexus" meeting report regarding dementia and cancer.

PMID- 28438507
TI  - Cardiothoracic Transplant Recipient Mycoplasma hominis: An Uncommon Infection
      with Probable Donor Transmission.
AB  - The role of infection with Mycoplasma hominis following cardiothoracic organ
      transplantation and its source of transmission have not been well-defined. Here,
      we identify and describe infection with M. hominis in patients following
      cardiothoracic organ transplantation after reviewing all cardiothoracic
      transplantations performed at our center between 1998 and July 2015. We found
      seven previously unreported cases of M. hominis culture positive infection all of
      whom presented with pleuritis, surgical site infection, and/or mediastinitis. PCR
      was used to establish the diagnosis in four cases. In two instances, paired
      single lung transplant recipients manifested infection, and in one of these
      pairs, isolates were indistinguishable by multilocus sequence typing (MLST). To
      investigate the prevalence of M. hominis in the lower respiratory tract, we
      tested 178 bronchoalveolar lavage (BAL) fluids collected from immunocompromised
      subjects for M. hominis by PCR; all were negative. Review of the literature
      revealed an additional 15 cases of M. hominis in lung transplant recipients, most
      with similar clinical presentations to our cases. We recommend that M. hominis
      should be considered in post-cardiothoracic transplant infections presenting with
      pleuritis, surgical site infection, or mediastinitis. M. hominis PCR may
      facilitate early diagnosis and prompt therapy. Evaluation for possible donor
      transmission should be considered.

PMID- 28438505
TI  - Turning down the volume: Astrocyte volume change in the generation and
      termination of epileptic seizures.
AB  - Approximately 1% of the global population suffers from epilepsy, a class of
      disorders characterized by recurrent and unpredictable seizures. Of these cases
      roughly one-third are refractory to current antiepileptic drugs, which typically
      target neuronal excitability directly. The events leading to seizure generation
      and epileptogenesis remain largely unknown, hindering development of new
      treatments. Some recent experimental models of epilepsy have provided compelling
      evidence that glial cells, especially astrocytes, could be central to seizure
      development. One of the proposed mechanisms for astrocyte involvement in seizures
      is astrocyte swelling, which may promote pathological neuronal firing and
      synchrony through reduction of the extracellular space and elevated glutamate
      concentrations. In this review, we discuss the common conditions under which
      astrocytes swell, the resultant effects on neural excitability, and how seizure
      development may ultimately be influenced by these effects.

PMID- 28438509
TI  - Effect of photodynamic therapy based on indocyanine green on expression of
      apoptosis-related genes in human gingival fibroblast cells.
AB  - BACKGROUND: Periodontal diseases refer to inflammation of the gingiva, induction
      of apoptosis in human gingival fibroblast cells, destruction of the surrounding
      tissues, and early bone loss resulting in infections due to the pathogenic
      activity of the microorganisms and the host immune inflammatory responses. Recent
      investigations have suggested that antimicrobial photodynamic therapy (aPDT) can
      be an adjunct treatment therapy for periodontal infections. AIM: To prove the
      lack of side effects of PDT on periodontal tissues, we investigated the
      expression of BAX and BCL-2 genes that are involved in apoptosis after the PDT on
      human gingival fibroblast (HGF) cells. MATERIALS AND METHODS: In this study the
      effect of PDT based on indocyanine green (ICG) as a photosensitizer with the
      diode laser were tested on the expression of BAX and BCL-2 genes in monolayers of
      HGF cells. The effects of PDT on the expression of BAX and BCL-2 genes were
      evaluated by real-time quantitative reverse transcription PCR. RESULTS: The
      results of the genes expression analysis revealed that ICG-PDT at concentrations
      1000MUg/mL, induced the significant expression of BAX in HGF cells; however, the
      laser irradiation as well as ICG showed no significant effects on the expression
      of these genes. Treatment with ICG alone, laser irradiation and ICG-PDT caused no
      observable BCL-2 gene expression changes between the tested and control groups.
      CONCLUSION: Our findings indicate that ICG-PDT at 1000MUg/mL of ICG with the
      exposure time of 60s for the diode laser would appear to be an inducer of
      apoptosis in HGF at transcriptome level.

PMID- 28438510
TI  - Disparities in the Management of Patients With Stage I Small Cell Lung Carcinoma
      (SCLC): A Surveillance, Epidemiology and End Results (SEER) Analysis.
AB  - INTRODUCTION: Patients with stage I small cell lung carcinoma (SCLC) are
      candidates for surgery; however, not much is known regarding the utilization of
      surgical resection in the management of stage I SCLC and the factors that
      determine the patient's ability to receive surgery. METHODS: The Surveillance,
      Epidemiology and End Results database was used to identify patients with stage I
      SCLC from 2007 to 2013. Continuous variables were compared with 1-way analysis of
      variance, and categorical variables were compared with chi2 testing.
      Multivariable logistic regression analyses were used to obtain odds ratios.
      RESULTS: Of the 1902 patients with stage I SCLC, 427 (22.4%) underwent resection,
      116 (6.1%) resection and radiation, 815 (42.8%) received radiation alone, and 544
      (28.6%) did not undergo surgery or radiation. Median overall survival for
      patients with surgery plus radiation was 60+ months, followed by surgery alone at
      50 months, radiation at 27 months, and no resection/radiation 16 months. Patients
      with >= 4 lymph nodes removed during surgery had better overall survival of 60+
      months compared with patients with < 4 lymph nodes removed (25 months); P < .001.
      Multivariate analysis demonstrated that elderly patients, men, African American
      individuals, Medicaid recipients, and patients with left-sided tumors were less
      likely to undergo resection. However, county-level socioeconomic factors, such as
      level of poverty, education, unemployment, and median income did not affect the
      likelihood of undergoing resection. CONCLUSIONS: Fewer than one-third of all
      patients with stage I SCLC undergo resection despite better outcomes with
      resection. Elderly African American men with Medicaid insurance were less likely
      to receive resection.

PMID- 28438511
TI  - Nitric oxide inhibits the mitochondrial carnitine/acylcarnitine carrier through
      reversible S-nitrosylation of cysteine 136.
AB  - S-nitrosylation of the mitochondrial carnitine/acylcarnitine transporter (CACT)
      has been investigated on the native and the recombinant proteins reconstituted in
      proteoliposomes, and on intact mitochondria. The widely-used NO-releasing
      compound, GSNO, strongly inhibited the antiport measured in proteoliposomes
      reconstituted with the native CACT from rat liver mitochondria or the recombinant
      rat CACT over-expressed in E. coli. Inhibition was reversed by the reducing agent
      dithioerythritol, indicating a reaction mechanism based on nitrosylation of Cys
      residues of the CACT. The half inhibition constant (IC50) was very similar for
      the native and recombinant proteins, i.e., 74 and 71MUM, respectively. The
      inhibition resulted to be competitive with respect the substrate, carnitine. NO
      competed also with NEM, correlating well with previous data showing interference
      of NEM with the substrate transport path. Using a site-directed mutagenesis
      approach on Cys residues of the recombinant CACT, the target of NO was
      identified. C136 plays a major role in the reaction mechanism. The occurrence of
      S-nitrosylation was demonstrated in intact mitochondria after treatment with
      GSNO, immunoprecipitation and immunostaining of CACT with a specific anti NO-Cys
      antibody. In parallel samples, transport activity of CACT measured in intact
      mitochondria, was strongly inhibited after GSNO treatment. The possible
      physiological and pathological implications of the post-translational
      modification of CACT are discussed.

PMID- 28438512
TI  - Physical performance, quality of life and sexual satisfaction evaluation in
      adults with cystic fibrosis: An unexplored correlation.
AB  - OBJECTIVE: Quality of life (QOL), sexual satisfaction (SS) and physical
      performance have been assessed in the management of numerous chronic diseases.
      METHODS: In this study, the following tests and surveys were applied: (i) QOL
      questionnaire [Cystic Fibrosis Questionnaire (CFQ)]; (ii) SS questionnaire (SSQ)
      [female sexual quotient (FSQ) and male sexual quotient (MSQ)]; (iii) 6-minute
      walk test (6MWT). Spearman's correlation was used for comparison between the
      data; the Mann-Whitney test was applied to analyze the difference between
      genders. A total of 52 adult patients with CF were included in this study.
      RESULTS: There was a positive correlation between CFQ domains and SSQ questions.
      The CFQ showed a positive correlation with peripheral oxygen saturation of
      hemoglobin (SpO2) and the distance walked in the 6MWT, and a negative correlation
      with the Borg scale. The SSQ showed positive correlation with the distance walked
      and a negative correlation with the Borg scale. For some markers evaluated in the
      6MWT, there was sometimes association with the evaluated domains and questions.
      Male patients showed better scores in the emotional CFQ domain, better
      performance in SSQ and physical performance. CONCLUSIONS: There was a correlation
      between CFQ, SSQ and 6MWT in CF. Finally; we believe that QOL surveys should
      assess the domain "sexuality" as well as physical performance tests.

PMID- 28438513
TI  - Rapid-Response Impulsivity Predicts Depression and Posttraumatic Stress Disorder
      Symptomatology at 1-Year Follow-Up in Blast-Exposed Service Members.
AB  - OBJECTIVE: To determine if elevated rapid-response impulsivity after blast
      exposure (as a putative marker of ventral prefrontal cortex [vPFC] damage) is
      predictive of future elevated affective symptomatology in blast-exposed service
      members. DESIGN: Longitudinal design with neurocognitive testing at initial
      assessment and 1-year follow-up assessment of psychiatric symptomatology by
      telephone interview. SETTING: Veterans Administration medical centers and
      postdeployment assessment centers at military bases. PARTICIPANTS: Blast-exposed
      U.S. military personnel (N=84) ages 19 to 39 years old. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Center for Epidemiological Studies-Depression
      Scale (CES-D) scores, Posttraumatic Stress Disorder Checklist Version 5 (PCL-5)
      scores, and Alcohol Use Disorders Identification Test-C (AUDIT-C) scores at the
      12-month follow-up telephone interview. RESULTS: After controlling for age and
      affective symptom scores reported at the initial assessment, commission errors on
      the Continuous Performance Test-II of the initial assessment were predictive of
      higher symptom scores on the CES-D and PCL-5 at follow-up, but were not
      predictive of AUDIT-C scores. CONCLUSIONS: Elevated rapid-response impulsivity,
      as a behavioral marker of reduced top-down frontocortical control, is a risk
      factor for elevated mood and posttraumatic stress disorder symptoms over time in
      blast-exposed individuals. Future longitudinal studies with predeployment
      neurobehavioral testing could enable attribution of this relation to blast
      related vPFC damage.

PMID- 28438514
TI  - Components of Standing Postural Control Evaluated in Pediatric Balance Measures:
      A Scoping Review.
AB  - OBJECTIVE: To identify measures of standing balance validated in pediatric
      populations, and to determine the components of postural control captured in each
      tool. DATA SOURCES: Electronic searches of MEDLINE, Embase, and CINAHL databases
      using key word combinations of postural balance/equilibrium,
      psychometrics/reproducibility of results/predictive value of tests, and
      child/pediatrics; gray literature; and hand searches. STUDY SELECTION: Inclusion
      criteria were measures with a stated objective to assess balance, with pediatric
      (<=18y) populations, with at least 1 psychometric evaluation, with at least 1
      standing task, with a standardized protocol and evaluation criteria, and
      published in English. Two reviewers independently identified studies for
      inclusion. There were 21 measures included. DATA EXTRACTION: Two reviewers
      extracted descriptive characteristics, and 2 investigators independently coded
      components of balance in each measure using a systems perspective for postural
      control, an established framework for balance in pediatric populations. DATA
      SYNTHESIS: Components of balance evaluated in measures were underlying motor
      systems (100% of measures), anticipatory postural control (72%), static stability
      (62%), sensory integration (52%), dynamic stability (48%), functional stability
      limits (24%), cognitive influences (24%), verticality (9%), and reactive postural
      control (0%). CONCLUSIONS: Assessing children's balance with valid and
      comprehensive measures is important for ensuring development of safe mobility and
      independence with functional tasks. Balance measures validated in pediatric
      populations to date do not comprehensively assess standing postural control and
      omit some key components for safe mobility and independence. Existing balance
      measures, that have been validated in adult populations and address some of the
      existing gaps in pediatric measures, warrant consideration for validation in
      children.

PMID- 28438515
TI  - Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with
      Thrombocytopenia.
AB  - OBJECTIVE: To determine the safety of intravenous (IV) recombinant tissue
      plasminogen activator (rtPA) in patients with acute ischemic stroke (AIS) who had
      a platelet count <100,000 /mm3. METHODS: We reviewed the charts of all patients
      who received IV rtPA for AIS during a 9.6-year period at our stroke center. Those
      with platelets <100,000/mm3 were identified. Head computed tomography scans
      performed in 24-36 hours postthrombolysis were reviewed to evaluate the rate of
      symptomatic intracranial hemorrhage (sICH). RESULTS: A total of 835 patients
      received IV rtPA for AIS during this period. A total of 5 patients were
      identified to have a platelet count <100,000/mm3. One of them (20%) developed
      sICH post-IV tPA administration .The mean platelet count of those 5 patients was
      63,000 +/- 19,000/mm3. To the best of our knowledge, only 21 thrombocytopenic
      patients have been reported to receive IV rtPA for AIS in the medical literature.
      Combining our 5 cases with 21 patients previously reported, we have 26 AIS
      patients who had a platelet count <100,000/mm3 and received IV rtPA, with 2 of
      them developing sICH (7.7 %). Comparing the rate of sICH among this group with
      the patients with normal platelet count in our cohort, there was no statistically
      significant difference (7.7% versus 6.04%, P value = .73). CONCLUSION: IV rtPA
      for AIS might be safe in patients with platelet count <100,000/mm3 and it is
      reasonable not to delay IV rtPA administration while waiting for the platelet
      count result, unless there is strong suspicion for abnormal platelet count.

PMID- 28438517
TI  - A high performing EEG approach for the automated scoring of the sleep stages of
      neonates.

PMID- 28438516
TI  - Global Transcriptomic Profiling of Cortex and Striatum: Cerebral Injury after
      Ischemia/Reperfusion in a Mouse Model.
AB  - OBJECTIVE: This study aims to investigate the molecular mechanism of injury
      development in the cortex and the striatum after cerebral ischemia/reperfusion
      (I/R). METHODS: Gene expression data (GSE23160) in the cortex and the striatum of
      an intraluminal middle cerebral artery occlusion-I/R mouse model (N = 12) and
      sham controls (N = 4) were downloaded from the Gene Expression Omnibus. Limma
      package was used to identify the differentially expressed genes (DEGs) between
      the I/R (2, 8, and 24 hours) and control groups. Correlation analysis was then
      performed to identify the highly correlated differentially expressed genes
      (HCDEGs). STRING and Cytoscape software were used to construct a protein-protein
      interaction (PPI) network of HCDEGs. Furthermore, Venny 2.0 was used to identify
      common overlapped DEGs whose transcription factors (TFs) were predicted using
      iRegulon in Cytoscape. RESULTS: For the cortex and the striatum, 2295 and 2282
      DEGs were respectively identified between the I/R group and the controls, and
      were classified into 3 and 2 correlation modules. For each module, a PPI network
      was constructed, and Toll-like receptor 2 (Tlr2, degree = 25), interleukin 1beta
      (Il1b, degree = 21), and heme oxygenase-1 (Hmox1, degree = 17) had high
      connective degrees. Furthermore, 29 common overlapped DEGs were found across time
      and tissue, which might be targeted by 13 TFs. Especially, Tlr2, Il1b, and Hmox1
      were targeted by myeloblastosis protein (Myb, target count = 16) and FBJ
      osteosarcoma protein (Fos, target count = 15). Moreover, plasminogen activator
      urokinase receptor (Plaur) was targeted by Fos, and it was an HCDEG in
      correlation modules of both cortex and striatum. Upregulation of Tlr2, Il1b,
      Hmox1, and Plaur in I/R injury was confirmed using quantitative polymerase chain
      reaction and immunohistochemical staining. CONCLUSION: Tlr2, Il1b, Hmox1, and
      Plaur regulated by Myb and Fos might participate in cortex and striatum injury
      after cerebral I/R.

PMID- 28438518
TI  - Testicular, spermatogenesis and sperm morphology in Martarega bentoi
      (Heteroptera: Notonectidae).
AB  - The testicular, spermatogenesis and sperm morphology of the backswimmer Martarega
      bentoi was described using light and transmission electron microscopy. In this
      species, a pair of testes, two deferent ducts, two different pairs of accessory
      glands, and an ejaculatory duct form the male reproductive system. Each testis
      consists of two testicular follicles, which are arranged side by side in snail
      shape. The follicles are filled with cysts at different stages of
      spermatogenesis, but in the same cyst the germ cells (up to 64) are in the same
      stage. At the end of spermatogenesis, the sperm cells are very long, with the
      flagellum measuring approximately 2500 MUm in length, the nucleus only 19 MUm,
      and the acrosome, with two distinct regions, 300 MUm. The flagellum is composed
      of an axoneme, with a 9 + 9 + 2 microtubular pattern, and 2 asymmetric
      mitochondrial derivatives (MDs). These have the anterior ends inserted into two
      cavities at the nucleus base, exhibit two paracrystalline inclusions, and have
      bridges linking them to the axoneme. Few spermatozoa per cyst, asymmetry in size
      and shape of the MDs, as well as their insertion at the nuclear base are
      characteristics considered derived, and that differentiate the sperm of M. bentoi
      from those of the Nepomorpha, Belostomatidae and Nepidae.

PMID- 28438519
TI  - Role of 18F-FDG PET/CT in primary brain lymphoma.
AB  - OBJECTIVE: To study the usefulness of 18F-FDG PET/CT in the initial evaluation
      and in the response assessment in primary brain lymphoma. MATERIAL AND METHODS: A
      retrospective analysis was carried out on 18 patients diagnosed with primary
      brain lymphoma, a histological subtype of diffuse large B-cell lymphoma, on whom
      an initial 18F-FDG PET/CT and MRI was performed, with 7 of the cases being
      analysed after the completion of treatment in order to assess response and
      clinical follow up. RESULTS: Initial 18F-FDG PET/CT showed 26 hypermetabolic
      foci, whereas 46 lesions were detected by MRI. The average SUV maximum of the
      lesions was 17.56 with T/N 3.55. The concordance of both tests for identifying
      the same number of lesions was moderate, obtaining a kappa index of 0.395
      (P<.001). In the evaluation of treatment, MRI identified 16 lesions compared to 7
      pathological accumulations observed by 18F-FDG PET/CT. The concordance of both
      tests to assess type of response to treatment was moderate (kappa index 0.41)
      (P=.04). In both the initial evaluation and the assessment of the response to
      treatment, PET/CT led to a change strategy in 22% of patients who had lesions
      outside the cerebral parenchyma. CONCLUSIONS: MRI appears to be the method of
      choice for detecting brain disease in patients with primary brain lymphoma,
      whereas 18F-FDG PET/CT seems to play a relevant role in the assessment of extra
      cerebral disease.

PMID- 28438520
TI  - Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects
      in cancer prognostic biomarkers.
AB  - Several reports over the last 10 years provided evidence that long noncoding RNAs
      (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200
      nucleotides and function as important regulators of gene expression, interacting
      with the major pathways of cell growth, proliferation, differentiation, and
      survival. A large number of lncRNAs has oncogenic function and is more expressed
      in tumor compared with normal tissues. Their overexpression may be associated
      with tumor formation, progression, and metastasis in a variety of tumors
      including bladder cancer. Although lncRNAs have been shown to have critical
      regulatory roles in cancer biology, the biological functions and prognostic
      values in nonmuscle-invasive bladder cancer remain largely unknown. Nevertheless,
      a growing body of evidence suggests that several lncRNAs expression profiles in
      bladder malignancies are associated with poor prognosis, and they can be detected
      in biological fluids, such as urines. Here, we review current progress in the
      biology and the implication of lncRNAs associated with bladder cancer, and we
      discuss their potential use as diagnosis and prognosis biomarkers in bladder
      malignancies with a focus on their role in high-risk nonmuscle-invasive tumors.

PMID- 28438522
TI  - Detection of Leishmania infantum DNA in conjunctival swabs of cats by
      quantitative real-time PCR.
AB  - Although some studies have investigated the potential role of cats as a reservoir
      for Leishmania, their role in the epidemiology of visceral leishmaniasis (VL) is
      still poorly understood. Molecular diagnostic techniques are an important tool in
      VL diagnosis, and PCR shows high sensitivity and specificity for Leishmania spp.
      detection. Quantitative real-time PCR (qPCR) is a method that permits
      quantitative analysis of a large number of samples, resulting in more sensitive,
      accurate, and reproducible measurements of specific DNA present in the sample.
      This study compared real-time PCR (qPCR) and conventional PCR (cPCR) for
      detection of Leishmania spp. in blood and conjunctival swab (CS) samples of
      healthy cats from a non-endemic area in the state of Sao Paulo, Brazil. Of all CS
      samples, 1.85% (2/108) were positive for Leishmania spp. by both cPCR as qPCR
      (kappa index = 1), indicating excellent agreement between the two methods. The
      DNA from the two CS-cPCR- and CS-qPCR-positive samples was further tested with a
      PCR test amplifying the Leishmania spp. discriminative rRNA internal transcribed
      spacer 1 (ITS 1), of which one sample generated a 300-350-bp DNA fragment whose
      size varies according to the Leishmania species. Following sequencing, the
      fragment showed 100% similarity to a GenBank L. infantum sequence obtained from a
      cat in Italy. In conclusion, the association of qPCR and CS proved to be
      effective for detection of Leishmania in cats. Conjunctival swab samples were
      shown to be a practical and better alternative to blood samples and may be useful
      in the diagnosis and studies of feline leishmaniasis.

PMID- 28438521
TI  - Modified dot-ELISA for diagnosis of human trichinellosis.
AB  - This study aimed to modify Dot-Enzyme-linked immunosorbent assay (dot-ELISA) for
      the diagnosis of human trichinellosis and to compare its performance with
      indirect ELISA and Western-blot assay (EITB). A total of 175 human serum samples
      were enrolled in the study. Indirect ELISA was used for the primary diagnosis.
      EITB versus fractionated 1st larval stage excretory-secretory antigens (TL-1 ESA)
      revealed three specific protein fractions at MW of 45, 50, and 55 kDa (kDa). Dot
      ELISA was performed in two ways. In the first one, sera were dotted on the
      separated three specific protein fractions, while in the second one the three
      fractions were eluted, concentrated at one pooled antigen that used in classic
      dot-ELISA. Both types of dot-ELISA proved absolute (100%) sensitivity and
      specificity in comparison with the gold standard EITB reaction. While sensitivity
      of ELISA was 100% and its specificity was 79.5%. The fraction at 45 kDa was the
      most sensitive one. The use of the pooled antigen improved the test results. The
      described dot-ELISA is an easy applicable diagnostic tool gathering the benefits
      of both ELISA and EITB.

PMID- 28438523
TI  - Predictors of Early Childbirth Among Female Adolescents in Foster Care.
AB  - PURPOSE: Placement into foster care is driven by a number of factors, many of
      which are associated with adolescent childbirth. Yet, there are few studies that
      identify the experiences and characteristics that predict adolescent childbirth
      among girls who spend time in foster care. METHODS: A longitudinal, population
      based data set was constructed by probabilistically matching California child
      protective service records for female foster youth to maternal information
      available on vital birth records for children born between 2001 and 2010. Rates
      of childbirth among girls in foster care after their 10th birthday were
      generated. Chi-square tests assessed differences and survival models were
      specified to determine the rate of childbearing across key characteristics.
      RESULTS: Among the 30,339 girls who spent time in foster care as adolescents,
      18.3% (5,567) gave birth for the first time before their 20th birthday. At a
      bivariate level, significant differences (p < .001) in birth rates were observed
      across demographic characteristics, maltreatment history, and foster care
      placement experiences. In the fully adjusted survival model, the highest birth
      rates were observed among girls who entered care between ages 13 and 16 years;
      had been in care for relatively short periods of time; lived in congregate care
      at the estimated date of conception; had a history of running away; and were
      Latina, black, or Native American. CONCLUSIONS: The results suggest that there
      are identifiable risk factors associated with early childbirth among girls in
      foster care, which can help determine the timing and location of reproductive
      health services to minimize unintended pregnancy and maximize adolescent health
      and well-being.

PMID- 28438524
TI  - Trajectories of Mental Health-Related Service Use Among Adolescents With
      Histories of Early Externalizing Problems.
AB  - PURPOSE: To inform efforts to reduce costly service utilization, the present
      study examined longitudinal trajectories of mental health-related outpatient and
      residential service use among at-risk youth with a history of early externalizing
      problems. METHODS: A cohort of 809 children in the Fast Track Project, a
      multisite longitudinal study of children at risk for conduct disorder, were
      followed prospectively from kindergarten through 12th grade. They resided in high
      risk areas with high rates of poverty, crime, and violence. Their outpatient and
      residential service use was assessed annually between sixth and 12th grades
      through parent report. Growth mixture modeling was applied to model individual
      differences in trajectories of service use during this period. Teacher, parent,
      and observer-reported childhood predictors of those trajectories were also
      examined. RESULTS: Most youths had minimal service use during preadolescence into
      adolescence. However, approximately 31% had moderate probability of using
      outpatient counseling services, and approximately 8% had elevated probability of
      seeing a family doctor for mental health needs. For residential services,
      approximately 6% had moderate to high probability of service use that peaked
      during transition to high school, whereas close to 5% had service use that
      dramatically increased during high school. Childhood predictors of these
      trajectories included earlier externalizing, internalizing, and emotion
      regulation problems. CONCLUSIONS: This study is the first to use person-centered
      analytic methods to examine longitudinal trajectories in mental health-related
      service use among at-risk adolescents. Timely treatment for severe externalizing
      problems, comorbid internalizing problems, and emotion dysregulation during
      childhood may be crucial for preventing chronic service use.

PMID- 28438525
TI  - Sociodemographic Factors Associated With Trans*female Youth's Access to Health
      Care in the San Francisco Bay Area.
AB  - PURPOSE: Trans*female youth (TFY) are an underserved population at risk for a
      variety of poor health outcomes, in part related to barriers to accessing health
      and mental health care. METHODS: We conducted a secondary analysis of data
      collected with 250 TFY aged 16-24 years in the San Francisco Bay Area from 2012
      to 2014. Logistic regression was used to test associations between
      sociodemographic variables and barriers to gender identity-based medical and
      mental health care. RESULTS: Having a history of unstable housing was associated
      with significantly higher odds of problems accessing both medical care (odds
      ratio: 2.16, 95% confidence interval: 1.12-4.13) and mental health care due to
      gender identity (odds ratio 2.65, 95% confidence interval: 1.08-6.45).
      Conversely, identifying as genderqueer/genderfluid, Latina, or living in
      dependent housing was associated with access to either medical or mental health
      care. CONCLUSIONS: Interventions are needed to address housing and discrimination
      barring access to health care among TFY.

PMID- 28438526
TI  - Emerging roles for ncRNAs in alcohol use disorders.
AB  - Chronic alcohol exposure produces widespread neuroadaptations and alterations in
      gene expression in human alcoholics and animal models. Technological advances in
      the past decade have increasingly highlighted the role of non-protein-coding RNAs
      (ncRNAs) in the regulation of gene expression and function. These recently
      characterized molecules were discovered to mediate diverse processes in the
      central nervous system, from normal development and physiology to regulation of
      disease, including alcoholism and other psychiatric disorders. This review will
      investigate the recent studies in human alcoholics and rodent models that have
      profiled different classes of ncRNAs and their dynamic alcohol-dependent
      regulation in brain.

PMID- 28438528
TI  - Molecular characterization of Kiss2 receptor and in vitro effects of Kiss2 on
      reproduction-related gene expression in the hypothalamus of half-smooth tongue
      sole (Cynoglossus semilaevis).
AB  - Kisspeptin (Kiss) and its receptor, KissR (previously known as GPR54), play a
      critical role in the control of reproduction and puberty onset in mammals.
      Additionally, a number of studies have provided evidence of the existence of
      multiple Kiss/KissR systems in teleosts, but the physiological relevance and
      functions of these kisspeptin forms (Kiss1 and Kiss2) still remain to be
      investigated. To this end, we examined the direct actions of Kiss2 on
      hypothalamic functions in the half-smooth tongue sole (Cynoglossus semilaevis), a
      representative species of the order Pleuronectiformes. As a first step, the full
      length cDNA for kiss2r was identified and kiss2r transcripts were shown to be
      widely expressed in various tissues, notably in the brain of tongue sole. Then,
      the effects of Kiss2 decapeptide on reproduction-related gene expression were
      evaluated using a primary hypothalamus culture system. Our results showed that
      neither gnrh2 nor gnrh3 mRNA levels were altered by Kiss2. However, Kiss2
      significantly increased the amounts of gnih and kiss2 mRNAs. In contrast, Kiss2
      elicited an evident inhibitory effect on both gnihr and kiss2r mRNA levels. To
      the best of our knowledge, this is the first description of a direct and
      differential regulation of reproduction-related gene expression by Kiss2 at the
      hypothalamus level of a teleost fish. Overall, this study provides novel
      information on the role of Kiss2/Kiss2R system in the reproductive function of
      teleosts.

PMID- 28438527
TI  - The BAF (BRG1/BRM-Associated Factor) chromatin-remodeling complex exhibits
      ethanol sensitivity in fetal neural progenitor cells and regulates transcription
      at the miR-9-2 encoding gene locus.
AB  - Fetal alcohol spectrum disorders are a leading cause of intellectual disability
      worldwide. Previous studies have shown that developmental ethanol exposure
      results in loss of microRNAs (miRNAs), including miR-9, and loss of these miRNAs,
      in turn, mediates some of ethanol's teratogenic effects in the developing brain.
      We previously found that ethanol increased methylation at the miR-9-2 encoding
      gene locus in mouse fetal neural stem cells (NSC), advancing a mechanism for
      epigenetic silencing of this locus and consequently, miR-9 loss in NSCs.
      Therefore, we assessed the role of the BAF (BRG1/BRM-Associated Factor) complex,
      which disassembles nucleosomes to facilitate access to chromatin, as an
      epigenetic mediator of ethanol's effects on miR-9. Chromatin immunoprecipitation
      and DNAse I-hypersensitivity analyses showed that the BAF complex was associated
      with both transcriptionally accessible and heterochromatic regions of the miR-9-2
      locus, and that disintegration of the BAF complex by combined knockdown of BAF170
      and BAF155 resulted in a significant decrease in miR-9. We hypothesized that
      ethanol exposure would result in loss of BAF-complex function at the miR-9-2
      locus. However, ethanol exposure significantly increased mRNA transcripts for
      maturation-associated BAF-complex members BAF170, SS18, ARID2, BAF60a,
      BRM/BAF190b, and BAF53b. Ethanol also significantly increased BAF-complex binding
      within an intron containing a CpG island and in the terminal exon encoding
      precursor (pre)-miR-9-2. These data suggest that the BAF complex may adaptively
      respond to ethanol exposure to protect against a complete loss of miR-9-2 in
      fetal NSCs. Chromatin remodeling factors may adapt to the presence of a
      teratogen, to maintain transcription of critical miRNA regulatory pathways.

PMID- 28438529
TI  - An ERP investigation of vertical reading fluency in Scrabble(r) experts.
AB  - Previous studies have found that competitive Scrabble expertise is associated
      with enhanced performance on visual lexical decision tasks (LDT), particularly
      for vertically presented stimuli. In the current study, we investigated the
      underlying mechanisms responsible for this vertical fluency. We examined
      behaviour and neural activity during LDT in 19 competitive Scrabble players and
      18 matched controls. Using event related potentials (ERP), we investigated
      whether Scrabble expertise modulates the N170, P300, and late positive component
      (LPC), associated with visual-orthographic processing, working memory, and
      stimulus classification, respectively. Behavioural results replicated those from
      previous studies: Scrabble experts were significantly faster than controls to
      respond to vertical stimuli in LDT. ERP results showed Scrabble experts had
      larger P300 amplitudes in right parietal electrodes compared to controls, as well
      as greater differentiation in LPC amplitudes between vertical words and nonwords.
      These findings suggest that the mechanism underlying vertical fluency in Scrabble
      experts involves enhanced domain-specific working memory and stimulus
      classification processes. The results have implications for understanding the
      flexibility of the adult visual word recognition system, as well as the
      behavioural and neural consequences of training within this system.

PMID- 28438530
TI  - Ferulic acid attenuates brain microvascular endothelial cells damage caused by
      oxygen-glucose deprivation via punctate-mitochondria-dependent mitophagy.
AB  - Ferulic acid (FA) has an important effect on scavenging free radicals, which is
      related to the alleviation of various neurodegenerative diseases. However, there
      are few studies about its effects on vascular dementia. In this study, we
      demonstrated the effect of FA on oxidative damage of brain microvascular
      endothelial cells (BMECs) which underwent oxygen-glucose deprivation (OGD) for
      2h. Our data showed that FA significantly reversed the oxidative stress state of
      OGD-treated BMECs and reduced mitochondrial dysfunction. In further study, we
      found that FA upregulated the expression of LC3-II, a marker of autophagy.
      Besides, mitophagy was observed by transmission electron microscopy. The
      mechanism of FA inducing autophagy was found to be related to mitochondrial
      fission, according to the effects of siRNA and inhibitor of dynamin-related
      protein 1, which was responsible for fission. All above suggested that FA
      mitigated OGD-induced mitochondrial oxidative damage by punctate-mitochondria
      dependent autophagy.

PMID- 28438531
TI  - Altered gray and white matter microstructure in Cushing's disease: A diffusional
      kurtosis imaging study.
AB  - Exposure to chronic hypercortisolism has multiple adverse effects on brain
      biology in humans. Cushing's disease (CD) represents a unique and natural human
      model for examining the effects of hypercortisolism on the brain. This cross
      sectional study used Diffusional Kurtosis Imaging (DKI) to investigate the
      microstructure alterations in both white matter (WM) and gray matter (GM) of CD
      patients and to determine the relationship of these changes with clinical
      characteristics. DKI images were obtained from 15 active CD patients. DKI
      parametric maps were estimated through voxel-based analyses (VBA) and compared
      with 15 healthy controls matched for age, sex and education. In addition,
      correlations were analyzed between the altered DKI parameters and clinical
      characteristics. Compared with healthy controls, CD patients mainly exhibited
      significantly altered diffuse parameters in the GM and WM of the left medial
      temporal lobe (MTL). The mean values of increased radial diffusivity (RD) of CD
      patients in GM of the left hippocampus/parahippocampal gyrus correlated
      positively with the clinical severity of CD. Additionally, we also found altered
      kurtosis parameters in the cerebellum and frontal lobe. DKI imaging of CD
      patients could represent complementary information in both white matter and gray
      matter. The impairment of the left MTL might explain some part of the memory and
      cognition impairments in CD patients.

PMID- 28438532
TI  - Kinetic properties and adrenergic control of TREK-2-like channels in rat medial
      prefrontal cortex (mPFC) pyramidal neurons.
AB  - TREK-2-like channels were identified on the basis of electrophysiological and
      pharmacological tests performed on freshly isolated and
      enzymatically/mechanically dispersed pyramidal neurons of the rat medial
      prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached
      configuration and the impact of adrenergic receptors (alpha1, alpha2, beta)
      stimulation on spontaneously appearing TREK-2-like channel activity was tested.
      The obtained results indicate that noradrenaline decreases the mean open
      probability of TREK-2-like channel currents by activation of beta1 but not of
      alpha1- and alpha2-adrenergic receptors. Mean open time and channel conductance
      were not affected. The system of intracellular signaling pathways depends on the
      activation of protein kinase A. We also show that adrenergic control of TREK-2
      like channel currents by adrenergic receptors was similar in pyramidal neurons
      isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans
      of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant
      in layer V pyramidal neurons. The role of TREK-2-like channel control by
      adrenergic receptors is discussed.

PMID- 28438533
TI  - Association of miR-145 With Statin-Induced Skeletal Muscle Toxicity in Human
      Rhabdomyosarcoma RD Cells.
AB  - Skeletal muscle toxicity including rhabdomyolysis in severe case is a major side
      effect of low-density lipoprotein cholesterol-lowering statin drugs. We,
      therefore, aimed at exploring microRNA (miRNA) expression to understand molecular
      mechanism of statin-induced toxicity. miRNA expression profiling assay for
      cerivastatin (1 MUM for 48 h)-treated RD cells showed more than 2-fold decrease
      in 26 miRNA expressions with miR-145 being downregulated prominently. When RD
      cells were treated with cerivastatin at 10 MUM for 36 h, mitochondrial
      dysfunction was observed in 49.6% of the population without causing apoptosis,
      whereas 82% underwent apoptosis when treated at 10 MUM for 48 h. In RD cells
      treated under the same condition (10 MUM for 48 h), miR-145 expression and mRNA
      expressions of proapoptotic APAF1 and CASP10 genes, potential targets of miR-145,
      significantly decreased and increased, respectively. Moreover, enforced
      expression of miR-145 reduced apoptotic cell population of cerivastatin-treated
      RD cells (10 MUM for 36 h). Because miR-145 increased in extracellular medium
      from cerivastatin-treated RD cells, miR-145 was suggested to be secreted in
      response to statin-induced toxicity. These results provide a new rationale for
      statin's toxicity that statin-induced apoptosis is caused by enhanced expression
      of proapoptotic genes mediated by decreased intracellular miR-145 due to statin
      induced mitochondrial dysfunction.

PMID- 28438534
TI  - Editorial.

PMID- 28438535
TI  - A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics.
AB  - Transport proteins expressed in the different barriers of the human body can have
      great implications on absorption, distribution, and excretion of drug compounds.
      Inhibition or saturation of a transporter can potentially alter these absorbtion,
      distribution, metabolism and elimination properties and thereby also the
      pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P
      gp, ABCB1) is an efflux transporter which is present in most of the barriers of
      the body, including the small intestine, the blood-brain barrier, the liver, and
      the kidney. In all these tissues, P-gp may mediate efflux of drug compounds and
      may also be a potential site for drug-drug interactions. Consequently, there is a
      need to be able to predict the saturation and inhibition of P-gp and other
      transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis
      has been applied to estimate kinetic parameters, such as Km and Vmax, for carrier
      mediated transport, whereas half-maximal inhibitor concentration (IC50) and the
      disassociation constant for an inhibitor/P-gp complex (Ki) have been determined
      to estimate P-gp inhibition. This review addresses in vitro methods commonly used
      to study P-gp transport kinetics and aims at providing a critical evaluation of
      the application of steady-state Michaelis-Menten analysis of kinetic parameters
      for substrate/P-gp interactions.

PMID- 28438536
TI  - Fatal pertussis in infancy, Italy.

PMID- 28438537
TI  - Special Issue of NeuroToxicology Dedicated to the late Toshio Narahashi: A
      Commentary from the Founding Editor/Editor-in-Chief of NeuroToxicology.

PMID- 28438538
TI  - Linking newborn severe combined immunodeficiency screening with targeted exome
      sequencing: A case report.

PMID- 28438539
TI  - Recurrent Acute Rhinosinusitis Prevention by Azithromycin in Children with
      Nonallergic Rhinitis.
AB  - BACKGROUND: Recurrent acute rhinosinusitis (RARS) is characterized by multiple
      episodes of acute rhinosinusitis between which symptoms and signs resolve
      completely. The role of antibiotic prophylaxis to prevent RARS in children with
      nonallergic rhinitis (NAR) has not been investigated. OBJECTIVE: To evaluate the
      effect of azithromycin to prevent RARS in children with NAR. METHODS: A
      randomized, double-blind, placebo-controlled study was conducted in NAR children
      (5-15 years) with RARS. Azithromycin (5 mg/kg/d) 3 d/wk for 12 months or placebo
      was assigned to the study group and the control group, respectively. Patients
      with allergic rhinitis were excluded. Number of rhinosinusitis episodes in 12
      months, visual analog scale score of nasal symptoms, and adjunctive medication
      score were recorded. RESULTS: Forty patients were enrolled and 20 patients were
      assigned randomly to the azithromycin and placebo groups. IgG subclass and
      specific antibody deficiencies were found in 83% and 2.5% of patients,
      respectively. After 12 months, the number of rhinosinusitis episodes/y in the
      azithromycin group reduced significantly from 5 to 0.5 (P < .001) in contrast to
      the placebo group. Number needed to treat using azithromycin prophylaxis to
      prevent 1 patient from having RARS was 2. The average visual analog scale score
      and the average adjunctive medication score in the azithromycin (but not in the
      placebo) group reduced significantly compared with baseline (2.2 +/- 1.4 vs 5.4
      +/- 1.8) and (3.9 +/- 1.7 vs 5.4 +/- 1.1), respectively (P < .001). CONCLUSIONS:
      Azithromycin prophylaxis can reduce the number of rhinosinusitis episodes and
      medication score, and improve nasal symptoms in NAR children with RARS.

PMID- 28438540
TI  - Potent and selective oxytocin receptor agonists without disulfide bridges.
AB  - Oxytocin (OT) is a neuropeptide involved in a wide variety of physiological
      actions, both peripherally and centrally. Many human studies have revealed the
      potential of OT to treat autism spectrum disorders and schizophrenia. OT
      interacts with the OT receptor (OTR) as well as vasopressin 1a and 1b receptors
      (V1aR, V1bR) as an agonist, and agonistic activity for V1aR and V1bR may have a
      negative impact on the therapeutic effects of OTR agonism in the CNS. An OTR
      selective agonistic peptide, FE 202767, in which the structural differences from
      OT are a sulfide bond instead of a disulfide bond, and N-alkylglycine replacement
      for Pro at position 7, was reported. However, the effects of amino acid
      substitutions in OT have not been comprehensively investigated to compare OTR,
      V1aR, and V1bR activities. This led us to obtain a new OTR-selective analog by
      comprehensive amino acid substitutions of OT and replacement of the disulfide
      bond. A systematic amino acid scanning (Ala, Leu, Phe, Ser, Glu, or Arg) of
      desamino OT (dOT) at positions 2, 3, 4, 5, 7, and 8 revealed the tolerability for
      the substitution at positions 7 and 8. Further detailed study showed that trans-4
      hydroxyproline (trans-Hyp) at position 7 and gamma-methylleucine [Leu(Me)] at
      position 8 were markedly effective for improving receptor selectivity without
      decreasing the potency at the OTR. Subsequently, a combination of these amino
      acid substitutions with the replacement of the disulfide bond of dOT analogs with
      a sulfide bond (carba analog) or an amide bond (lactam analog) yielded several
      promising analogs, including carba-1-[trans-Hyp7,Leu(Me)8]dOT (14) with a higher
      potency (7.2pM) at OTR than that of OT and marked selectivity (>10,000-fold) over
      V1aR and V1bR. Hence, we investigated comprehensive modification of OT and
      obtained new OT analogs that exhibited high potency at OTR with marked
      selectivity. These OTR-selective agonists could be useful to investigate OTR
      mediated effects on psychiatric disorders.

PMID- 28438541
TI  - Synthesis, structural characterization and biological activity of novel
      Knoevenagel condensates on DLD-1 human colon carcinoma.
AB  - Biologically active Knoevenagel condensates (1-14) of diarylheptanoids: 1,7-bis(3
      methoxy-4-hydroxyphenyl)hepta-1,7-diene-3,5-dione and 1,7-bis(3-ethoxy-4
      hydroxyphenyl)hepta-1,7-diene-3,5-dione, were synthesized and structurally
      characterized. Compounds 1-14 exhibited cytotoxicity against colon carcinoma
      cells, and their antiproliferative effect was associated with a significant
      decrease of multidrug resistance proteins. One of the underlying mechanisms of
      these effects is the reduction of intracellular and extracellular SOD enzymes by
      compounds 1, 12 and 14, which render the tumor cells more vulnerable to oxidative
      stress.

PMID- 28438542
TI  - Identification of low micromolar dual inhibitors for aldose reductase (ALR2) and
      poly (ADP-ribose) polymerase (PARP-1) using structure based design approach.
AB  - Clinical studies have revealed that diabetic retinopathy is a multifactorial
      disorder. Moreover, studies also suggest that ALR2 and PARP-1 co-occur in retinal
      cells, making them appropriate targets for the treatment of diabetic retinopathy.
      To find the dual inhibitors of ALR2 and PARP-1, the structure based design was
      carried out in parallel for both the target proteins. A series of novel
      thiazolidine-2,4-dione (TZD) derivatives were therefore rationally designed,
      synthesized and their in vitro inhibitory activities against ALR2 and PARP-1 were
      evaluated. The experimental results showed that compounds 5b and 5f, with 2
      chloro and 4-fluoro substitutions, showed biochemical activities in micromolar
      and submicromolar range (IC50 1.34-5.03MUM) against both the targeted enzymes.
      The structure-activity relationship elucidated for these novel inhibitors against
      both the enzymes provide new insight into the binding mode of the inhibitors to
      the active sites of enzymes. The positive results of the biochemical assay
      suggest that these compounds may be further optimized and utilized for the
      treatment of diabetic retinopathy.

PMID- 28438544
TI  - Reply to the letter to the editor on "No modulatory effects by tSMS when
      delivered during a cognitive task".

PMID- 28438545
TI  - No modulatory effects by tSMS when delivered during a cognitive task.

PMID- 28438543
TI  - Modulation of motor cortex excitability predicts antidepressant response to
      prefrontal cortex repetitive transcranial magnetic stimulation.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) targeting the
      left dorsolateral prefrontal cortex (DLPFC) is a treatment option for patients
      with medication-resistant major depressive disorder (MDD). However,
      antidepressant response is variable and there are currently no response
      predictors with sufficient accuracy for clinical use. OBJECTIVE: We report on
      results of an observational open-label study to determine whether the modulatory
      effect of 10 Hz motor cortex (MC) rTMS is predictive of the antidepressant effect
      of 10 Hz DLPFC rTMS. METHODS: Fifty-one medication-resistant MDD patients were
      enrolled for a 10-day treatment course of DLPFC rTMS and antidepressant response
      was assessed according to post-treatment reduction of the 17-item Hamilton Rating
      Scale for Depression score. Prior to treatment, we assessed the modulation of
      motor evoked potential (MEP) amplitude by MC rTMS. MEP's were induced with single
      TMS pulses and measured using surface electromyography. MEP modulation was
      calculated as the change of mean MEP amplitude after MC rTMS. RESULTS: MEP
      modulation proved to be a robust predictor of reduction of clinician-rated
      depression severity following the course of DLPFC rTMS: larger MC rTMS-induced
      increase of corticospinal excitability anticipated a better antidepressant
      response. This was found both in univariate analyses (Spearman regression: rho =
      0.43, p < 0.005) and a multivariable linear regression model (beta = 0.25, p <
      0.0001) controlling for baseline depression severity, age and resting motor
      threshold. CONCLUSIONS: These findings suggest that MC rTMS-induced modulation of
      corticospinal excitability warrants further evaluation as a potential predictive
      biomarker of antidepressant response to left DLPFC 10 Hz rTMS.

PMID- 28438546
TI  - Clinical predictors of remission and persistence of adult-onset asthma.
AB  - BACKGROUND: Adult-onset asthma is an important but relatively understudied asthma
      phenotype and little is known about its natural course and prognosis. The
      remission rate is believed to be low, and it is still obscure which factors
      predict remission or persistence of the disease. OBJECTIVE: This study sought to
      determine the remission rate and identify predictors of persistence and remission
      of adult-onset asthma. METHODS: Two hundred adult patients with recently
      diagnosed (<1 year) asthma were recruited from secondary and tertiary pulmonary
      clinics and prospectively followed for 5 years. Clinical, functional, and
      inflammatory parameters were assessed at baseline and at yearly visits. Asthma
      remission was defined as absence of asthma symptoms for >=1 year and no asthma
      medication use for >=1 year. Descriptive statistics and logistic regression
      analysis were performed. RESULTS: Five-year follow-up data of 170 patients (85%)
      was available. Of these, 27 patients (15.9%) experienced asthma remission.
      Patients with asthma persistence were older, had worse asthma control, required
      higher doses of inhaled corticosteroids, had more severe airway
      hyperresponsiveness, more often nasal polyps, and higher levels of blood
      neutrophils as compared to patients who experienced clinical remission. In a
      multivariable logistic regression analysis, only moderate to severe bronchial
      hyperresponsiveness and nasal polyps were independent predictors of asthma
      persistence. Patients with these 2 characteristics had <1% chance of asthma
      remission. CONCLUSIONS: One in 6 patients with adult-onset asthma experiences
      remission within the first 5 years of the disease. In patients with moderate to
      severe bronchial hyperresponsiveness and nasal polyposis, the chance of remission
      is close to zero.

PMID- 28438547
TI  - Metformin is associated with a lower risk of colorectal cancer in Taiwanese
      patients with type 2 diabetes: A retrospective cohort analysis.
AB  - BACKGROUND: The association between metformin and colorectal cancer (CRC) has
      rarely been investigated in Asian populations. METHODS: This retrospective cohort
      study included patients with newly diagnosed type 2 diabetes during 1999-2005,
      recruited from Taiwan's National Health Insurance database. A total of 169,601
      patients (original cohort: 153,270 ever-users and 16,331 never-users of
      metformin) and a subgroup of 1:1 propensity-score-matched pairs of 16,331 ever
      users and 16,331 never-users (matched cohort) were followed up to 31 December
      2011. Cox regression was constructed with the inverse probability of treatment
      weighting, using propensity scores, and was used to estimate hazard ratios (HRs).
      RESULTS: In the original cohort, the incidence of CRC was 242.9 and 480.9 per
      100,000 person-years, respectively, in ever- and never-users. The overall HR
      [0.50, 95% confidence interval (CI): 0.45-0.56] suggested a significantly lower
      risk in metformin users, while compared with never-users, the HR (95% CI) for the
      first (<27.1 months), second (27.1-58.1 months) and third (>58.1 months) tertiles
      of cumulative duration of metformin therapy was 0.86 (0.76-0.98), 0.51 (0.45
      0.59) and 0.26 (0.23-0.30), respectively. Analyses in the matched cohort showed
      similar findings with an overall HR of 0.62 (0.53-0.74), and a tertile analysis
      HR of 1.02 (0.81-1.28), 0.70 (0.56-0.89) and 0.32 (0.23-0.43), respectively. Re
      analyses using more stringent diagnoses of CRC and cumulative duration as a
      continuous variable have consistently supported a protective effect with
      metformin use. CONCLUSION: Metformin is associated with a lower frequency of CRC.

PMID- 28438548
TI  - Promoting toddlers' vegetable consumption through interactive reading and
      puppetry.
AB  - Picture books with characters that promote healthy eating are increasingly being
      used to make this behavior more attractive. The first aim of this study was to
      investigate whether the effect of vegetable-promoting picture books on toddlers'
      vegetable consumption differed according to the reading style and the use of a
      hand puppet during reading. The second aim was to investigate whether these
      effects were mediated by toddlers' narrative involvement and character imitation.
      In a 2 (reading style: interactive vs. passive) x 2 (puppet use: with vs. without
      puppet) between-subjects design, 163 toddlers (2-3 years) were randomly assigned
      to one of the four reading conditions. The story was about a rabbit that loves to
      eat carrots. After the fourth reading day, the eating task was conducted in which
      children could eat freely from four different snacks, including carrots. The main
      finding was that interactive reading produced the greatest carrot consumption.
      The explanation for this effect was that interactive reading stimulated toddlers
      to imitate poses of the book characters, even more when interactive reading was
      supported by the use of a hand puppet. The findings underline that young children
      should be actively involved with health interventions in order for them to be
      effective.

PMID- 28438549
TI  - Poly (methyl vinyl ether-co-maleic acid) - Pectin based hydrogel-forming systems:
      Gel, film, and microneedles.
AB  - Cross-linking of natural and synthetic polymers is widely explored to achieve the
      desired material properties (mechanical strength, drug loading capacity, swelling
      and erosion rates). However, the potential of polymers produced by crosslinking
      poly (methyl vinyl ether-co-maleic acid) (PMVE/MA) and pectin (PE) in
      pharmaceutics is mainly unexplored so far. We have investigated the effect of
      various esterification conditions and pectin content on the physicochemical
      properties. Materials have been characterized by fourier transform infrared,
      differential scanning calorimetry and scanning electron microscopy. In addition,
      swelling and bioadhesive features of PMVE/MA-PE hydrogel systems were
      investigated. A band shift for the carbonyl group from 1706 to 1776cm-1, and
      glass transition (Tg) increased from 55.4+/-0.9 degrees C to 119.5+/-0.3 degrees
      C confirmed the formation of esterification reaction within the cross-linked
      films. Cross-linked PMVE/MA:PE films with a ratio of 5 demonstrated a superior
      mass increase when compared to 2.5, 3.125, 3.75, 6.25, and 7.5 ratios of the same
      hydrogel film. Formulations containing PMVE/MA and pectin with a ratio of 3.75
      showed superior bioadhesive features. For the first time, we engineered three
      dimensional printing based swell-able microneedle arrays made out of cross-linked
      PMVE/MA-PE. Microneedle arrays height and aspect ratio were ranged from 702.5+/
      11.9MUm to 726+/-23.3MUm and 3.12+/-0.20 to 3.29+/-0.21, respectively. Cross
      linked PMVE/MA-PE Microneedle arrays (10-2, 24h) indicated the least height loss,
      22.33+/-4.15%, during axial compression test; whilst, transverse failure of cross
      linked PMVE/MA-PE Microneedle arrays was varied from 0.15+/-0.05 to 0.25+/
      0.04N/needle. In conclusion, we obtained a novel cross-linked polymer system with
      promising features of drug delivery and bio-analytical applications.

PMID- 28438550
TI  - Lipophilic salts of poorly soluble compounds to enable high-dose lipidic SEDDS
      formulations in drug discovery.
AB  - Self-emulsifying drug delivery systems (SEDDS) have been used to solubilize
      poorly water-soluble drugs to improve exposure in high-dose pharmacokinetic (PK)
      and toxicokinetic (TK) studies. However, the absorbable dose is often limited by
      drug solubility in the lipidic SEDDS vehicle. This study focuses on increasing
      solubility and drug loading of ionizable drugs in SEDDS vehicles using lipophilic
      counterions to prepare lipophilic salts of drugs. SEDDS formulations of two
      lipophilic salts-atazanavir-2-naphthalene sulfonic acid (ATV-2-NSA) and
      atazanavir-dioctyl sulfosuccinic acid (ATV-Doc)-were characterized and their
      performance compared to atazanavir (ATV) free base formulated as an aqueous
      crystalline suspension, an organic solution, and a SEDDS suspension, using in
      vitro, in vivo, and in silico methods. ATV-2-NSA exhibited ~6-fold increased
      solubility in a SEDDS vehicle, allowing emulsion dosing at 12mg/mL. In rat PK
      studies at 60mg/kg, the ATV-2-NSA SEDDS emulsion had comparable exposure to the
      free-base solution, but with less variability, and had better exposure at high
      dose than aqueous suspensions of ATV free base. Trends in dose-dependent exposure
      for various formulations were consistent with GastroPlusTM modeling. Results
      suggest use of lipophilic salts is a valuable approach for delivering poorly
      soluble compounds at high doses in Discovery.

PMID- 28438551
TI  - Development of a buccal doxepin platform for pain in oral mucositis derived from
      head and neck cancer treatment.
AB  - This study describes the development of semisolid formulations containing doxepin
      (DOX) for pain relief in oral mucositis, frequently related to chemotherapy
      and/or radiotherapy treatments in patients with head and neck cancer. Chemical
      permeation enhancers were evaluated and selected according to the results
      obtained from rheological studies, drug release, and drug permeation and
      retention through buccal mucosa. Finally, the selected formulation was compared
      in vivo, with a reference DOX mouthwash, whose clinical efficacy had been
      previously reported. The obtained findings showed that an orabase(r) platform
      loading transcutol(r) (10%) and menthol (5%) for the buccal vehiculization of DOX
      exhibited a decreased elastic and viscous behavior improving its application. The
      main drug release mechanism could be considered as diffusion according to Higuchi
      model. Obtained DOX permeation rates were considered optimal for an analgesic
      effect and far below to an antidepressant activity. Similar in vivo plasma
      concentrations were found for the semisolid formulation and the reference
      mouthwash. However, DOX amounts retained in the mucosa of animals for the
      semisolid formulation were higher than the reference, which let us hypostatize
      even stronger potential local therapeutic effect with additional advantages such
      as, mucoadhesive properties, absence of alcohol, some degree of freshness, as
      well as, drug palatability improvement.

PMID- 28438553
TI  - Human leukocyte antigen class I (A, B and C) allele and haplotype variation in a
      South African Mixed ancestry population.
AB  - South Africa has a large (~53million), ethnically diverse population (black
      African, Caucasian, Indian/Asian and Mixed ancestry) and a high disease burden
      (particularly HIV-1 and Mycobacterium tuberculosis). The Mixed ancestry
      population constitutes ~9% of the total population and was established ~365years
      ago in the Western Cape region through interracial mixing of black Africans,
      Europeans and Asians. Admixed populations present unique opportunities to
      identify genetic factors involved in disease susceptibility. Since HLA genes are
      important mediators of host immunity, we investigated HLA-A, -B and -C allele and
      haplotype diversity in 50 healthy, unrelated individuals recruited from the Mixed
      ancestry population.

PMID- 28438554
TI  - Interleukin-17F and interleukin-6 gene polymorphisms in Asian Indian patients
      with Takayasu arteritis.
AB  - OBJECTIVES: To assess genetic association between single nucleotide polymorphisms
      (SNPs) in genes encoding T-helper cytokines and Takayasu Arteritis (TA)
      susceptibility in Asian Indian population. METHODS: In Phase-1, the genomic DNA
      of 120 TA patients and 119 healthy controls were genotyped for SNPs rs1800795
      (interleukin (IL)-6), rs763780 (IL-17F), rs1800871, rs1800872, rs1800896 (IL-10)
      and rs1800468, rs1800469, rs1800470 (transforming growth factor-beta). Allele
      frequencies between cases and controls were compared using chi-squared test and
      also reassessed empirically (pe) by 10,000 permutations. In Phase-2, additional
      98 TA patients and 101 controls were genotyped for replicating the significant
      associations noted in Phase-1 of the study. RESULTS: All 8 SNPs in Phase 1 were
      in Hardy-Weinberg proportions. The G allele at rs763780 (IL-17F) was
      significantly associated with TA (p=0.014). We also found that rs1800795 (IL-6)
      was associated with tuberculosis (p=0.001) under a dominant model. In Phase-2
      replication part of the study, the rs763780 showed a trend towards association
      with TA (p=0.08), and the magnitude and direction of the odds ratio (OR) also
      were consistent with results of Phase-1. In the combined analysis, protective
      association of the G allele of rs763780 with TA was again significant [OR (95%
      CI)=0.44 (0.25-0.77); p=0.0029]. The G allele was also significantly associated
      (p<0.05) with underlying tuberculosis (TB) and occurrence of syncope in TA.
      CONCLUSION: G allele of rs763780 in IL-17F gene was protectively associated
      against susceptibility to TA. GG genotypes of rs1800795 in IL-6 was also
      associated with occurrence of tuberculosis in our patients with TA.

PMID- 28438552
TI  - Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines.
AB  - Pro-inflammatory cytokines promote autoimmune inflammation and tissue damage,
      while anti-inflammatory cytokines help resolve inflammation and facilitate tissue
      repair. Over the past few decades, this general feature of cytokine-mediated
      events has offered a broad framework to comprehend the pathogenesis of autoimmune
      and other immune-mediated diseases, and to successfully develop therapeutic
      approaches for diseases such as rheumatoid arthritis (RA). Anti-tumor necrosis
      factor-alpha (TNF-alpha) therapy is a testimony in support of this endeavor.
      However, many patients with RA fail to respond to this or other biologics, and
      some patients may suffer unexpected aggravation of arthritic inflammation or
      other autoimmune effects. These observations combined with rapid advancements in
      immunology in regard to newer cytokines and T cell subsets have enforced a re
      evaluation of the perceived pathogenic attribute of the pro-inflammatory
      cytokines. Studies conducted by others and us in experimental models of arthritis
      involving direct administration of IFN-gamma or TNF-alpha; in vivo neutralization
      of the cytokine; the use of animals deficient in the cytokine or its receptor;
      and the impact of the cytokine or anti-cytokine therapy on defined T cell subsets
      have revealed paradoxical anti-inflammatory and immunoregulatory attributes of
      these two cytokines. Similar studies in other models of autoimmunity as well as
      limited studies in arthritis patients have also unveiled the disease-protective
      effects of these pro-inflammatory cytokines. A major mechanism in this regard is
      the altered balance between the pathogenic T helper 17 (Th17) and protective T
      regulatory (Treg) cells in favor of the latter. However, it is essential to
      consider that this aspect of the pro-inflammatory cytokines is context-dependent
      such that the dose and timing of intervention, the experimental model of the
      disease under study, and the differences in individual responsiveness can
      influence the final outcomes. Nevertheless, the realization that pro-inflammatory
      cytokines can also be immunoregulatory offers a new perspective in fully
      understanding the pathogenesis of autoimmune diseases and in designing better
      therapies for controlling them.

PMID- 28438555
TI  - Amygdala activity associated with social choice in mice.
AB  - Studies suggest that the amygdala is a key region for regulation of anxiety, fear
      and social function. Therefore, dysfunction of the amygdala has been proposed as
      a potential mechanism for negative symptoms in schizophrenia. This may be due to
      NMDA receptor-mediated hypofunction, which is thought to be related to the
      pathogenesis of schizophrenia. In this study, electroencephalographic amygdala
      activity was assessed in mice during the three-chamber social test. This activity
      was also evaluated following exposure to the NMDA receptor antagonist ketamine.
      Vehicle-treated mice spent significantly more time in the social than the non
      social chamber. This social preference was eliminated by ketamine. However,
      ketamine-treated mice spent significantly less time in the social chamber and
      significantly more time in the nonsocial chamber than vehicle-treated mice. There
      were no significant differences in induced powers between social and non-social
      chamber entries in vehicle-treated mice, except for theta frequencies, which
      featured greater induced theta power during non-social chamber entry. Ketamine
      eliminated differences in induced theta power between social and non-social
      chamber entries. Moreover, ketamine increased the induced gamma power during
      social chamber entry compared to that of vehicle-treated mice. All other
      frequency ranges were not significantly influenced by zone or drug condition. All
      significant findings were upon entry to chambers not during interaction. Results
      suggest that impaired function of NMDA receptor-mediated glutamate transmission
      can induce social impairments and amygdala dysfunction, similar to the pattern in
      schizophrenia. Future studies will utilize this method to evaluate mechanisms of
      social dysfunction and development of treatments of social impairments in
      schizophrenia.

PMID- 28438556
TI  - The brain and the subjective experience of time. A voxel based symptom-lesion
      mapping study.
AB  - The aim of the study was to identify the anatomical bases involved in the
      subjective experience of time, by means of a voxel based symptom-lesion mapping
      (VLSM) study on patients with focal brain damage. Thirty-three patients (nineteen
      with right-hemisphere lesions -RBD, and fourteen with left lesion- LBD) and
      twenty-eight non-neurological controls (NNC) underwent the semi-structured
      QUEstionnaire for the Subjective experience of Time (QUEST) requiring
      retrospective and prospective judgements on self-relevant time intervals. All
      participants also completed tests to assess general cognitive functioning and two
      questionnaires to evaluate their emotional state. Both groups of brain-damaged
      patients achieved significantly different scores from NNC on the time
      performance, without differences between RBD and LBD. VLSM showed a cluster of
      voxels located in the right inferior parietal lobule significantly related to
      errors in the prospective items. The lesion subtraction analysis revealed two
      different patterns possibly associated with errors in the prospective items (the
      right inferior parietal cortex, rolandic operculum and posterior middle temporal
      gyrus) and in the retrospective items (superior middle temporal gyrus, white
      matter posterior to the insula).

PMID- 28438557
TI  - The isozyme selective phosphodiesterase-4 inhibitor, ABI-4, attenuates the
      effects of lipopolysaccharide in human cells and rodent models of peripheral and
      CNS inflammation.
AB  - Inhibitors of phosphodiesterase-4 (PDE4) have been approved for the treatment of
      inflammatory disorders, but are associated with dose-limiting nausea and
      vomiting. These side effects are hypothesized to be mediated by inhibition of the
      PDE4D isozyme. Here we demonstrate the anti-inflammatory effects of the novel
      brain penetrant PDE4D-sparing PDE4 inhibitor, ABI-4. ABI-4 was a potent
      (EC50~14nM) inhibitor of lipopolysaccharide (LPS) induced TNF-alpha release from
      mouse microglia and human PBMCs. ABI-4 (0.32mg/kg) blocked LPS-induced release of
      pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6) in blood and brain of
      mice. In a rat model of endotoxin induced uveitis, ABI-4 (0.03-0.3mg/kg)
      demonstrated steroid-like efficacy in preventing leucocyte infiltration of the
      aqueous humor when administered 4h after LPS. LPS (0.32mg/kg*5days) caused a 30%
      upregulation of translocator protein (TSPO) binding which was prevented by co
      administration of ABI-4 (0.32mg/kg). In a paradigm to assess motivation, LPS
      (0.32mg/kg) reduced the number of rewards received, whereas the effect was
      significantly blunted in mice dosed with ABI-4 (P<0.05) or in PDE4B-/- mice.
      PDE4B was also shown to modulate brain and plasma levels of TNF-alpha and IL
      1beta in aged mice. Aged mice dosed chronically with ABI-4 (0.32mg/kg) as well as
      aged PDE4B-/- mice, had significantly lower levels of TNF-alpha and IL-1beta in
      brain and plasma relative to vehicle treated or PDE4+/+ mice. Together these data
      demonstrate that the PDE4D sparing, PDE4 inhibitor, ABI-4 retains potency and
      efficacy in exerting anti-inflammatory effects. This mechanism warrants further
      investigation in human disorders involving neuroinflammation.

PMID- 28438558
TI  - Cooling Down Thermomorphogenesis by UV-B Signaling.
AB  - PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) is a key transcriptional regulator
      promoting plant responses to elevated ambient temperatures. A recent study
      reported that the ultraviolet B radiation (UV-B) photoreceptor UVR8 signaling
      pathway inhibits PIF4 via multiple mechanisms to repress plant responses to high
      ambient temperatures.

PMID- 28438559
TI  - The role of copper nanoparticles in an etch-and-rinse adhesive on antimicrobial
      activity, mechanical properties and the durability of resin-dentine interfaces.
AB  - OBJECTIVES: To evaluate the effect of addition of copper nanoparticles at
      different concentrations into an etch-and-rinse adhesive (ER) on antimicrobial
      activity, Knoop microhardness (KHN), in vitro and in situ degree of conversion
      (DC), as well as the immediate (IM) and 2-year (2Y) resin-dentine bond strength
      (MUTBS) and nanoleakage (NL). METHODS: Seven experimental ER adhesives were
      formulated according to the amount of copper nanoparticles incorporated into the
      adhesives (0 [control], 0.0075 to 1wt.%). We tested the antimicrobial activity of
      adhesives against Streptococcus mutans using agar diffusion assay after IM and
      2Y. The Knoop microhardness and in vitro DC were tested after IM and 2Y. The
      adhesives were applied to flat occlusal dentine surfaces after acid etching.
      After resin build-ups, specimens were longitudinally sectioned to obtain beam
      like resin-dentine specimens (0.8mm2), which were used for evaluation of MUTBS
      and nanoleakage at the IM and 2Y periods. In situ DC was evaluated at the IM
      period in these beam-like specimens. Data were submitted to appropriate
      statistical analyses (alpha=0.05). RESULTS: The addition of copper nanoparticles
      provided antimicrobial activity to the adhesives only in the IM evaluation and
      slightly reduced the KHN, the in vitro and in situ DC (copper concentrations of
      1wt.%). However, KHN increase for all concentrations after 2Y. After 2Y, no
      significant reductions of MUTBS (0.06 to 1% wt.%) and increases of nanoleakage
      were observed for copper containing adhesives compared to the control group.
      CONCLUSION: Copper nanoparticles addition up to 0.5wt.% may provide antimicrobial
      properties to ER adhesives and prevent the degradation of the adhesive interface,
      without reducing the mechanical properties of the formulations.

PMID- 28438560
TI  - Longitudinal investigation of salivary proteomic profiles in the development of
      early childhood caries.
AB  - OBJECTIVES: To investigate differentially expressed salivary peptides in the
      development of early childhood caries (ECC) in 3-4 year-old children. MATERIALS
      AND METHODS: Eighty-two caries-free children at baseline were followed-up for
      1year, during which period 15 of them had developed ECC (Group C), whilst another
      15 cases out of the 31 individuals who remained healthy were marked as Group H.
      Stimulated whole saliva samples were collected at 0, 6 and 12 months, and
      analyzed using weak cation exchange magnetic beads combined with matrix assisted
      laser desorption/ionization time-of-flight mass spectrometry. Corresponding
      peptide mass fingerprints were obtained to develop a discriminating model for ECC
      development. Q-Exactive mass spectrometry was then performed to identify the
      possible proteins where these peptides might derive from. RESULTS: Nine peptide
      peaks were found to be significantly different in Group C among the three
      sampling time points and might correlate with development of caries. Levels of
      three of them increased over time, whilst that of the other six decreased
      gradually. We chose three peptides (1346.6, 2603.5 and 3192.8Da) which exhibited
      the best capability of classification, to establish a model for children at high
      risk of caries. One peptide (1346.6Da) was identified to be salivary histatin
      rich peptide. CONCLUSIONS: Our results indicate that peptidomic methods can be
      applied to help identify new candidate biomarkers for the occurrence and
      development of ECC. CLINICAL SIGNIFICANCE: The change of salivary peptides may be
      an indicator of ECC, facilitating more effective measures to be taken in
      prevention of this disease.

PMID- 28438561
TI  - Cryopreservation of oil palm (Elaeis guineensis Jacq.).
AB  - Oil palm (Elaeis guineensis Jacq.), a tropical plant, is the leading source of
      edible oil. This review deals with the cryopreservation of oil palm as a way to
      preserve this important tropical germplasm. Somatic embryos have been the most
      popular source of material for cryopreservation as they are propagules that are
      effectively produced during micropropagation. In contrast, fewer studies exist on
      the cryopreservation of pollen, zygotic embryos, seeds, kernels and embryogenic
      cell suspensions. This review highlights the ideal protocols, in detail, in a bid
      to offer guidance for further advances in oil palm cryopreservation.

PMID- 28438562
TI  - First successful vitrification of salmonid ovarian tissue.
AB  - Due to a lack of cryopreservation protocols for fish eggs and embryos,
      alternative techniques which will enable storage of female genetic resources are
      crucial for future development of reproduction management in conservation biology
      and aquaculture. Experiments were conducted to develop an optimal vitrification
      protocol for cryopreservation of brown trout Salmo trutta juvenile ovarian
      tissue. Needle immersed vitrification (NIV) method was used where ovaries were
      pinned on an acupuncture needle, passaged through equilibration and vitrification
      solutions containing different combinations and concentrations of methanol
      (MeOH), propylene glycol (PG) and dimethyl sulfoxide (Me2SO) and subsequently
      plunged into liquid nitrogen. Vitrification solutions containing equal
      cryoprotectant concentrations (3M Me2SO and 3M PG) yielded the highest oogonia
      survival rates (up to 40%) and qualitatively and quantitatively unaltered
      perinucleolar follicles. The method developed for brown trout could be applied to
      the conservation of female genetic resources of other salmonid species, including
      endangered and endemic species or populations.

PMID- 28438563
TI  - Voiding dysfunction after isolated cerebellum stroke in a teenager.

PMID- 28438564
TI  - Essential oil of Artemisia argyi suppresses inflammatory responses by inhibiting
      JAK/STATs activation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi is a herbal medicine
      traditionally used in Asia for the treatment of bronchitis, dermatitis and
      arthritis. Recent studies revealed the anti-inflammatory effect of essential oil
      in this plant. However, the mechanisms underlying the therapeutic potential have
      not been well elucidated. The present study is aimed to verify its anti
      inflammatory effect and investigate the probable mechanisms. MATERIALS AND
      METHODS: The essential oil from Artemisia argyi (AAEO) was initially tested
      against LPS-induced production of inflammatory mediators and cytokines in
      RAW264.7 macrophages. Protein and mRNA expressions of iNOS and COX-2 were
      determined by Western blotting and RT-PCR analysis, respectively. The effects on
      the activation of MAPK/NF-kappaB/AP-1 and JAK/STATs pathway were also
      investigated by western blot. Meanwhile, in vivo anti-inflammatory effect was
      examined by histologic and immunohistochemical analysis in TPA-induced mouse ear
      edema model. RESULTS: The results of in vitro experiments showed that AAEO dose
      dependently suppressed the release of pro-inflammatory mediators (NO, PGE2 and
      ROS) and cytokines (TNF-alpha, IL-6, IFN-beta and MCP-1) in LPS-induced RAW264.7
      macrophages. It down-regulated iNOS and COX-2 protein and mRNA expression but did
      not affect the activity of these two enzymes. AAEO significantly inhibited the
      phosphorylation of JAK2 and STAT1/3, but not the activation of MAPK and NF-kappaB
      cascades. In animal model, oral administration of AAEO significantly attenuated
      TPA-induced mouse ear edema and decreased the protein level of COX-2. CONCLUSION:
      AAEO suppresses inflammatory responses via down-regulation of the JAK/STATs
      signaling and ROS scavenging, which could contribute, at least in part, to the
      anti-inflammatory effect of AAEO.

PMID- 28438565
TI  - Improvements in oocyte competence in superovulated mice following treatment with
      cilostazol: Ovulation of immature oocytes with high developmental rates.
AB  - Exogenous administration of superovulatory hormones negatively affects oocyte
      competence in mammals. Phosphodiesterase 3A inhibitors were found to improve
      competence of oocytes matured in vitro in several species, including humans. This
      study was therefore designed to define oocyte maturation synchronization and
      competence, in vivo, using superovulated mice treated with cilostazol, a
      selective phosphodiesterase 3A inhibitor. Swiss Webster mice were superovulated
      and treated orally with 7.5mg cilostazol once or twice to result in ovulation of
      immature oocytes at the metaphase I (MI) or germinal vesicle (GV) stage,
      respectively. Control immature oocytes were recovered from preovulatory follicles
      of superovulated mice not treated with cilostazol. Treated GV oocytes had
      significantly higher rates of synchronized and advanced chromatin configuration
      and cortical granule distribution than did control GV oocytes. Treated GV oocytes
      had a moderate increase in cAMP levels and consequently higher rates of meiotic
      maturation, IVF, and blastocyst formation than did control GV oocytes (P<0.0001).
      Treated MI oocytes had higher rates of normal spindles and chromosomes aligned at
      the metaphase plate than did control MI oocytes (P<0.003). Treated mice ovulating
      MI oocytes produced litter sizes larger than those observed in control mice
      ovulating mature oocytes (P<0.002). This study reveals that synchronization of
      oocyte maturation in superovulated mice improves oocyte development and
      competence. The capability of cilostazol, a clinically approved medication, to
      improve mouse oocyte competence suggests the potential benefit of including this
      compound in ovarian hyperstimulation programs to improve in vitro fertilization
      outcomes in infertile women.

PMID- 28438566
TI  - T-type voltage gated calcium channels are involved in endothelium-dependent
      relaxation of mice pulmonary artery.
AB  - In pulmonary arterial endothelial cells, Ca2+ channels and intracellular Ca2+
      concentration ([Ca2+]i) control the release of vasorelaxant factors such as
      nitric oxide and are involved in the regulation of pulmonary arterial blood
      pressure. The present study was undertaken to investigate the implication of T
      type voltage-gated Ca2+ channels (T-VGCCs, Cav3.1 channel) in the endothelium
      dependent relaxation of intrapulmonary arteries. Relaxation was quantified by
      means of a myograph in wild type and Cav3.1-/- mice. Endothelial [Ca2+]i and NO
      production were measured, on whole vessels, with the fluo-4 and DAF-fm probes.
      Acetylcholine (ACh) induced a nitric oxide- and endothelium-dependent relaxation
      that was significantly reduced in pulmonary arteries from Cav3.1-/- compared to
      wild type mice as well as in the presence of T-VGCC inhibitors (NNC 55-0396 or
      mibefradil). ACh also increased endothelial [Ca2+]i and NO production that were
      both reduced in Cav3.1-/- compared to wild type mice or in the presence of T-VGCC
      inhibitors. Immunofluorescence labeling revealed the presence of Cav3.1 channels
      in endothelial cells that co-localized with endothelial nitric oxide synthase in
      arteries from wild type mice. TRPV4-, beta2 adrenergic- and nitric oxide donors
      (SNP)-mediated relaxation were not altered in Cav3.1-/- compared to wild type
      mice. Finally, in chronically hypoxic mice, a model of pulmonary hypertension,
      ACh relaxation was reduced but still depended on Cav3.1 channels activity. The
      present study thus demonstrates that T-VGCCs, mainly Cav3.1 channel, contribute
      to intrapulmonary vascular reactivity in mice by controlling endothelial [Ca2+]i
      and ACh-mediated relaxation.

PMID- 28438568
TI  - A novel mutation in pmrB mediates colistin resistance during therapy of
      Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a highly versatile nosocomial pathogen. Multidrug
      resistance among A. baumannii isolates led to the use of colistin, subsequently
      giving rise to colistin-resistant strains. In this study, the genetic and
      phenotypic profiles of two colistin-resistant A. baumannii isolates were
      investigated. Two A. baumannii isolates were obtained from Patient 1 (C071 and
      C440) and three isolates were obtained from Patient 2 (C080, C314 and C428).
      Susceptibility profiles were determined by VITEK(r)2 and Etest. Clonality was
      determined by RAPD analysis and trilocus multiplex PCR. The pmrCAB operon was
      sequenced and common carbapenemase genes were screened for by PCR. Doubling
      times, haemolysis, surface motility, biofilm formation, siderophore production
      and proteolytic activity were phenotypically determined. Finally, whole-genome
      sequencing was performed for all five isolates. Isolates C440 and C428 were
      resistant to colistin and were clonally identical to their sensitive
      counterparts. The cause of colistin resistance was traced to the previously
      described P233S mutation in pmrB of C440 and to a novel DeltaI19 mutation in pmrB
      of C428. blaOXA-58-like and blaGES-5 from the strains of Patients 1 and 2,
      respectively, were also detected. C440 had attenuated proteolytic activity and
      was positive for siderophore production compared with C071. No difference in in
      vitro virulence was detected between isolates C080, C314 and C428. In conclusion,
      one common and one novel mutation were encountered in pmrB from two distinct
      colistin-resistant A. baumannii isolates. These mutations caused colistin
      resistance during therapy in two distinct clones, and only one of them had
      altered in vitro virulence.

PMID- 28438567
TI  - A systematic evaluation of microRNAs in regulating human hepatic CYP2E1.
AB  - Cytochrome P450 2E1 (CYP2E1) is an important drug metabolizing enzyme for
      processing numerous xenobiotics in the liver, including acetaminophen and
      ethanol. Previous studies have shown that microRNAs (miRNAs) can suppress CYP2E1
      expression by binding to the 3'-untranslated region (3'-UTR) of its transcript.
      However, a systematic analysis of CYP2E1 regulation by miRNAs has not been
      described. Here, we applied in silico, in vivo, and in vitro approaches to
      investigate miRNAs involved in the regulation of CYP2E1. Initially, potential
      miRNA binding sites in the CYP2E1 mRNA transcript were identified and screened
      using in silico methods. Next, inverse correlations were found in human liver
      samples between the expression of CYP2E1 mRNA and the levels of two miRNA
      species, hsa-miR-214-3p and hsa-miR-942-5p. In a HepG2-derived CYP2E1 over
      expression cell model, hsa-miR-214-3p exhibited strong suppression of CYP2E1
      expression by targeting the coding region of its mRNA transcript, but hsa-miR-942
      5p did not inhibit CYP2E1 levels. Electrophoretic mobility shift assays confirmed
      that hsa-miR-214-3p recruited other cellular protein factors to form stable
      complexes with specific sequences present in the CYP2E1 mRNA open reading frame.
      Transfection of HepaRG cells with hsa-miR-214-3p mimics inhibited expression of
      the endogenous CYP2E1 gene. Further, hsa-miR-214-3p mimics partially blocked
      ethanol-dependent increases in CYP2E1 mRNA and protein levels in HepG2 cells and
      they reduced the release of alanine aminotransferase from CYP2E1-overexpressing
      HepG2 cells exposed to acetaminophen. These results substantiate the suppressing
      effect of hsa-miR-214-3p on CYP2E1 expression.

PMID- 28438569
TI  - Methylprednisolone liver toxicity: A new case and a French regional
      pharmacovigilance survey.
AB  - Reported hepatotoxicity induced by corticosteroids is very rare, and the
      diagnosis is highly challenging in the context of auto-immune disease. We report
      here a case of high-dose methylprednisolone (MP)-induced acute hepatitis
      confirmed by liver histology in a patient with multiple sclerosis (MS) and a case
      series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5
      cases, other common causes of hepatitis were excluded. The causal relationship
      with MP pulse therapy was supported by the fact that MP was the only culprit
      drug. In addition, 3 of these 5 patients underwent unintended single or multiple
      positive MP rechallenge. Our 5 patients scored a RUCAM score from 6 (probable) to
      10 (highly probable). MP-induced liver injury is probably very rare, since only
      less than 30 cases have been reported in the literature. Nevertheless, our cases
      strongly illustrates that many cases could have been unrecognized; final
      diagnosis in 3 of 5 of our patients was made after the second or third episode of
      acute hepatitis. In conclusion, these cases we report here strongly illustrates
      that high-dose MP-induced liver injury can occur in patients treated for MS or
      auto-immune disorder. Unintended re-challenge can confirm the diagnosis and can
      help to distinguish it from autoimmune hepatitis. Performing liver function tests
      routinely both before and after MP administration would be beneficial, as the
      timely recognition of this complication and early drug withdrawal may prevent
      progression of severe necrosis hepatic injury.

PMID- 28438570
TI  - Analysis of intrahepatic total HBV DNA, cccDNA and serum HBsAg level in Chronic
      Hepatitis B patients with undetectable serum HBV DNA during oral antiviral
      therapy.
AB  - BACKGROUND: This study aimed to investigate the relationship between intrahepatic
      cccDNA and serum HBsAg in chronic Hepatitis B (CHB) patients with undetectable
      serum HBV DNA during antiviral therapy. METHODS: We investigated HBsAg serum
      levels and their relationship to intrahepatic total cccDNA and HBV DNA in CHB
      patients with undetectable serum HBV DNA during oral antiviral therapy.
      Intrahepatic cccDNA and HBV DNA quantitation were performed in the same needle
      biopsy material, while serum HBsAg, HBeAg and HBV DNA levels were measured in
      samples drawn on the day of the liver biopsy. RESULTS: A total of 90 patients who
      had a liver biopsy were enrolled, including 80 patients with CHB and 10 patients
      with liver cirrhosis (LC). All the CHB patients were divided into HBeAg-positive
      and HBeAg-negative group. By using real-time PCR detection, we found that
      intrahepatic cccDNA and HBV DNA levels were higher in CHB patients than those in
      LC patients (Intrahepatic cccDNA: 6.15+/-1.19 vs. 6.12+/-0.36, HBV DNA: 7.26+/
      0.49 vs. 5.59+/-0.45, both P<0.05). Intrahepatic cccDNA level was positively
      correlated with serum HBsAg in HBeAg-negative (r=0.66, P=0.02) and lower serum
      HBeAg (<=50S/CO) CHB patients (r=0.47, P=0.03), but not in higher serum HBeAg
      (>50S/CO) CHB patients (both P>0.05). In HBeAg negative patients, serum HBsAg
      level was correlated with intrahepatic total HBV DNA level (r=0.52, P=0.006).
      However, no relationship between HBsAg level and intrahepatic total HBV DNA level
      was found in HBeAg positive patients (both P>0.05). CONCLUSIONS: Serum HBsAg can
      be used to predict intrahepatic cccDNA and HBV DNA level in CHB patients with low
      serum HBeAg statues, especially in HBeAg negative patients.

PMID- 28438572
TI  - Co-administration of tenofovir plus protease inhibitor based antiretroviral
      therapy during sofosbuvir/ledipasvir treatment for HCV infection: Much Ado About
      Nothing?

PMID- 28438573
TI  - From the Editor: Preventing cardiovascular death.

PMID- 28438571
TI  - Effect of intestinal epithelial autophagy on bacterial translocation in severe
      acute pancreatitis.
AB  - BACKGROUND AND OBJECTIVE: We examined the impact of autophagy activation on
      bacterial translocation (BT) and tight junction (TJ) proteins in the intestinal
      mucosa of patients with severe acute pancreatitis (SAP). METHODS: Thirty-one SAP
      patients were divided into two groups, BT(+) and BT(-), according to the presence
      of BT in the blood, as detected by 16S rDNA sequencing. Eight healthy individuals
      were included in the control group. Serum endotoxin levels were measured by
      ELISA. Colonic mucosal tissue was obtained by endoscopy, and the TJ proteins and
      phosphatidylethanolamine-conjugated microtubule-associated protein light chain 3
      (LC3-II) were analyzed using immunofluorescence and Western blotting. RESULTS:
      The expression of LC3II in patients with SAP was higher than that observed in
      healthy controls. Patients who tested positive for the presence of BT had a
      higher level of claudins-2 (CL-2) and a lower level of occludin and Zonula
      occluden-1 (ZO-1) than BT(-) patients. Moreover, the levels of LC3II in BT(-)
      patients was higher than that found in BT(+) patients, and occludin and ZO-1 were
      positively correlated with LC3II. CONCLUSIONS: Autophagy activation in the
      intestinal epithelial cells of patients with SAP and its effects on BT may act
      through enhancing para-cellular TJs.

PMID- 28438574
TI  - Extreme hypertriglyceridemia, pseudohyponatremia, and pseudoacidosis in a neonate
      with lipoprotein lipase deficiency due to segmental uniparental disomy.
AB  - Extreme hypertriglyceridemia is rare in the neonatal period. We report a neonate
      with lipoprotein lipase (LPL) deficiency who presented with diagnostic and
      management conundrum. A full-term 36-day-old female was noted to have "Pepto
      Bismol like" blood when repeating a newborn screening. The initial plasma
      triglyceride level was 24,318 mg/dL. The laboratory tests revealed serum
      bicarbonate level of <5 mmol/L, sodium of 127 mmol/L, and severe anemia. There
      were no signs of acute distress. The point of care capillary blood testing,
      however, demonstrated normal serum pH (7.2), bicarbonate (25.4 mmol/L), and
      sodium (139 mmol/L). The patient had mild elevation of serum lactic acid and no
      ketonuria. A diagnosis of type I hyperlipoproteinemia was made. Oral feeding was
      stopped, and the infant received intravenous fluids for the next 7 days resulting
      in lowering of serum triglyceride levels to 1016 mg/dL. Oral feeding was
      initiated with an amino acid-rich formula to which medium chain triglycerides
      were slowly added, while maintaining the total fat content to <15% of total daily
      energy. Sequencing of the LPL gene revealed a homozygous c.644G>A, p.(Gly215Glu)
      mutation. Subsequent analysis of the parental samples revealed that only the
      father, but not the mother, was a heterozygous carrier of the same mutation.
      Analysis of 18 informative microsatellite markers on chromosome 8 revealed
      paternal segmental uniparental disomy with partial absence of the maternal
      chromosome 8p, confirmed by single-nucleotide polymorphism microarray. We
      conclude that besides pseudohyponatremia, extreme hypertriglyceridemia can rarely
      present as pseudoacidosis and uniparental disomy can be an underlying mechanism
      for autosomal recessive diseases such as LPL deficiency.

PMID- 28438575
TI  - Multiple symmetric lipomatosis and gynecomastia: A case report and relative
      literature review.
AB  - Multiple symmetric lipomatosis is a rare disease characterized by a symmetrical
      accumulation of massive adipose tissue on the neck, the superior part of the
      trunk, and limbs. Here, we reported an extremely rare case of multiple symmetric
      lipomatosis in a 46-year-old Chinese man, who has a history of heavy drinking and
      smoking and presented with diffuse lipomatosis and bilateral breast enlargement.
      Hyperuricemia and impaired glucose tolerance test were all found in this patient.
      A brief review of the literature was also made in this article.

PMID- 28438576
TI  - Arabidopsis MADS-Box Transcription Factor AGL21 Acts as Environmental
      Surveillance of Seed Germination by Regulating ABI5 Expression.
AB  - Seed germination is a crucial checkpoint for plant survival under unfavorable
      environmental conditions. Abscisic acid (ABA) signaling plays a vital role in
      integrating environmental information to regulate seed germination. It has been
      well known that MCM1/AGAMOUS/DEFICIENS/SRF (MADS)-box transcription factors are
      key regulators of seed and flower development in Arabidopsis. However, little is
      known about their functions in seed germination. Here we report that MADS-box
      transcription factor AGL21 is a negative regulator of seed germination and post
      germination growth by controlling the expression of ABA-INSENSITIVE 5 (ABI5) in
      Arabidopsis. The AGL21-overexpressing plants were hypersensitive to ABA, salt,
      and osmotic stresses during seed germination and early post-germination growth,
      whereas agl21 mutants were less sensitive. We found that AGL21 positively
      regulated ABI5 expression in seeds. Consistently, genetic analyses showed that
      AGL21 is epistatic to ABI5 in controlling seed germination. Chromatin
      immunoprecipitation assays further demonstrated that AGL21 could directly bind to
      the ABI5 promoter in plant cells. Moreover, we found that AGL21 responded to
      multiple environmental stresses and plant hormones during seed germination. Taken
      together, our results suggest that AGL21 acts as a surveillance integrator that
      incorporates environmental cues and endogenous hormonal signals into ABA
      signaling to regulate seed germination and early post-germination growth.

PMID- 28438577
TI  - Genomic CG dinucleotide deficiencies associated with transposable element
      hypermutation in Basidiomycetes, some lower fungi, a moss and a clubmoss.
AB  - Many Basidiomycete genomes include substantial fractions that are deficient in CG
      dinucleotides, in extreme cases amounting to 70% of the genome. CG deficiency is
      variable and correlates with genome size and, more closely, with transposable
      element (TE) content. Many species have limited CG deficiency; it is therefore
      likely that there are other mechanisms that can control TE proliferation.
      Examination of TEs confirms that C-to-T transition mutations in CG dinucleotides
      may comprise a conspicuous proportion of differences between paired elements,
      however transition/transversion ratios are never as high as those due to RIP in
      some Ascomycetes, suggesting that repeat-associated CG mutation is not totally
      pervasive. This has allowed gene family expansion in Basidiomycetes, although CG
      transition differences are often prominent in paired gene family members, and are
      evidently responsible for destruction of some copies. A few lower fungal genomes
      exhibit similar evidence of repeat-associated CG mutation, as do the genomes of
      the two lower plants Physcomitrella patens and Selaginella moellendorffii, in
      both of which mutation parallels published methylation of CHG as well as CG
      nucleotides. In Basidiomycete DNA methylation has been reported to be largely
      confined to CG dinucleotides in repetitive DNA, but while methylation and
      mutation are evidently associated, it is not clear which is cause and which
      effect.

PMID- 28438578
TI  - Global cerebral ischemia in rats leads to amnesia due to selective neuronal death
      followed by astroglial scar formation in the CA1 layer.
AB  - Global Cerebral Ischemia (GCI) occurs following cardiac arrest or neonatal
      asphyxia and leads to harmful neurological consequences. In most cases, patients
      who survive cardiac arrest develop severe cognitive and motor impairments. This
      study focused on learning and memory deficits associated with brain
      neuroanatomical reorganization that appears after GCI. The four-vessel occlusion
      (4VO) model was performed to produce a transient GCI. Hippocampal lesions in
      ischemic rats were visualized using anatomical Magnetic Resonance Imaging (aMRI).
      Then, the learning and memory abilities of control and ischemic (bilaterally or
      unilaterally) rats were assessed through the olfactory associated learning task.
      Finally, a "longitudinal" histological study was carried out to highlight the
      cellular reorganizations occurring after GCI. We demonstrated that the imaging,
      behavioral and histological results are closely related. In fact, aMRI revealed
      the appearance of hyper-intense signals in the dorsal hippocampus at day 3 post
      GCI. Consequently, we showed a rise in cell proliferation (Ki 67+ cells) and
      endogenous neurogenesis especially in the dentate gyrus (DG) at day 3 post-GCI.
      Then, hyper-intense signals in the dorsal hippocampus were confirmed by strong
      neuronal losses in the CA1 layer at day 7 post-GCI. These results were linked
      with severe learning and memory impairments only in bilaterally ischemic rats at
      day 14 post-GCI. This amnesia was accompanied by huge astroglial and microglial
      hyperactivity at day 30 post-GCI. Finally, Nestin+ cells and astrocytes gave rise
      to astroglial scars, which persisted 60days post-GCI. In the light of these
      results, the 4VO model appears a reliable method to produce amnesia in order to
      study and develop new therapeutic strategies.

PMID- 28438579
TI  - The BRENDA enzyme information system-From a database to an expert system.
AB  - Enzymes, representing the largest and by far most complex group of proteins, play
      an essential role in all processes of life, including metabolism, gene
      expression, cell division, the immune system, and others. Their function, also
      connected to most diseases or stress control makes them interesting targets for
      research and applications in biotechnology, medical treatments, or diagnosis.
      Their functional parameters and other properties are collected, integrated, and
      made available to the scientific community in the BRaunschweig ENzyme DAtabase
      (BRENDA). In the last 30 years BRENDA has developed into one of the most highly
      used biological databases worldwide. The data contents, the process of data
      acquisition, data integration and control, the ways to access the data, and
      visualizations provided by the website are described and discussed.

PMID- 28438580
TI  - First complete genome sequence of Bacillus glycinifermentans B-27.
AB  - The first complete genome sequence of Bacillus glycinifermentans B-27 was
      determined by SMRT sequencing generating a genome sequence with a total length of
      4,607,442 bases. Based on this sequence 4738 protein-coding sequences were
      predicted and used to identify gene clusters that are related to the production
      of secondary metabolites such as Lichenysin, Bacillibactin and Bacitracin. This
      genomic potential combined with the ability of B. glycinifermentans B-27 to grown
      in bile containing media might contribute to a future application of this strain
      as probiotic in productive livestock potentially inhibiting competing and
      pathogenic organisms.

PMID- 28438581
TI  - Many Palliative Medicine Team Recommendations Are Not Implemented by the
      Consulting Team. A Study of One Academic Medical Center.

PMID- 28438582
TI  - The Moment of Death.

PMID- 28438583
TI  - Psychometric Assessment of the Chinese Version of the Abbreviated Expanded
      Prostate Cancer Index Composite (EPIC-26) and the Clinical Practice Version (EPIC
      CP) in Chinese Men With Prostate Cancer.
AB  - PURPOSE: The Expanded Prostate Cancer Index Composite (EPIC) instrument was
      designed to assess a range of health-related quality-of-life issues specifically
      relevant to patients with prostate cancer. This study examined the validity and
      reliability of Chinese versions of the 26-item EPIC and of the 16-item EPIC for
      Clinical Practice (EPIC-CP) in Chinese patients with prostate cancer. MATERIALS
      AND METHODS: A Chinese version of the 26-item EPIC and the 16-item EPIC-CP were
      self-completed by 252 Chinese patients with prostate cancer who were recruited
      from three community-based cancer service centers. Confirmatory factors analysis
      assessed the factor structures of the EPIC and the EPIC-CP. Internal consistency
      and construct and clinical validities of the factor structures were assessed.
      RESULTS: Confirmatory factor analysis revealed that the original factor structure
      of both EPIC-26 and EPIC-CP showed good fit to this sample. A correlated model
      was superior to a hierarchical model in both EPIC-26 and EPIC-CP supporting the
      utility of the domain scores over the total scores. Cronbach alpha ranged from
      0.55 to 0.91 for EPIC-26 and 0.44 to 0.67 for EPIC-CP. Construct validity was
      supported by correlations between EPIC-26/EPIC-CP and psychological distress
      measures. Clinical validity was supported by differentiation between patients
      with and without prostatectomy. CONCLUSIONS: These Chinese versions of the five
      factor EPIC-26 and the EPIC-CP are valid and practical measures for assessing a
      range of health-related quality-of-life issues related to the diagnosis and
      treatment of prostate cancer, highlighting their utility in assessing health
      related quality of life for patients diagnosed with prostate cancer.

PMID- 28438584
TI  - Strategies for Enhancing Family Participation in Research in the ICU: Findings
      From a Qualitative Study.
AB  - CONTEXT: Family members of critically ill patients who participate in research
      focused on palliative care issues have been found to be systematically different
      from those who do not. These differences threaten the validity of research and
      raise ethical questions about worsening disparities in care by failing to
      represent diverse perspectives. OBJECTIVES: This study's aims were to explore: 1)
      barriers and facilitators influencing family members' decisions to participate in
      palliative care research; and 2) potential methods to enhance research
      participation. METHODS: Family members who were asked to participate in a
      randomized trial testing the efficacy of a facilitator to improve clinician
      family communication in the intensive care unit (ICU). Family members who
      participated (n = 17) and those who declined participation (n = 7) in Family
      Communication Study were interviewed about their recruitment experiences. We also
      included family members of currently critically ill patients to assess current
      experiences (n = 4). Interviews were audio-recorded and transcribed.
      Investigators used thematic analysis to identify factors influencing family
      members' decisions. Transcripts were co-reviewed to synthesize codes and themes.
      RESULTS: Three factors influencing participants' decisions were identified:
      Altruism, Research Experience, and Enhanced Resources. Altruism and Research
      Experience described intrinsic characteristics that are less amenable to
      strategies for improving participation rates. Enhanced Resources reflects
      families' desires for increased access to information and logistical and
      emotional support. CONCLUSION: Family members found their recruitment experiences
      to be positive when staff were knowledgeable about the ICU, sensitive to the
      stressful circumstances, and conveyed a caring attitude. By training research
      staff to be supportive of families' emotional needs and need for logistical
      knowledge about the ICU, recruitment of a potentially more diverse sample of
      families may be enhanced.

PMID- 28438585
TI  - Reply to Serin et al.

PMID- 28438586
TI  - Discharge to Subacute Rehabilitation Facilities Does Not Benefit Patients
      Hospitalized With Progressive Gastrointestinal Cancer.

PMID- 28438587
TI  - Intranasal Vinegar as an Effective Treatment for Persistent Hiccups in a Patient
      With Advanced Cancer Undergoing Palliative Care.

PMID- 28438588
TI  - Inferring Palliative Intent From Administrative Data: Validation of a Claims
      Based Case Definition for Venting Gastrostomy Tube.

PMID- 28438590
TI  - Antibiotic prophylaxis in cataract surgery in the setting of penicillin allergy:
      A decision-making algorithm.
AB  - Cataract surgery is the most commonly performed surgical procedure in many
      developed countries. Postoperative endophthalmitis is a rare complication with
      potentially devastating visual outcomes. Currently, there is no global consensus
      regarding antibiotic prophylaxis in cataract surgery despite growing evidence of
      the benefits of prophylactic intracameral cefuroxime at the conclusion of
      surgery. The decision about which antibiotic regimen to use is further
      complicated in patients reporting penicillin allergy. Historic statistics
      suggesting crossreactivity of penicillins and cephalosporins have persisted into
      modern surgery. It is important for ophthalmologists to consider all available
      antibiotic options and have an up-to-date knowledge of antibiotic crossreactivity
      when faced with the dilemma of choosing appropriate antibiotic prophylaxis for
      patients undergoing cataract surgery with a history of penicillin allergy. Each
      option carries risks, and the choice may have medicolegal implications in the
      event of an adverse outcome. We assess the options for antibiotic prophylaxis in
      cataract surgery in the setting of penicillin allergy and provide an algorithm to
      assist decision-making for individual patients.

PMID- 28438589
TI  - Specialty Palliative Care Consultations for Nursing Home Residents With Dementia.
AB  - CONTEXT: U.S. nursing home (NH) residents with dementia have limited access to
      specialty palliative care beyond Medicare hospice. OBJECTIVES: The objective of
      this study was to examine the value of expanded palliative care access for NH
      residents with moderate-to-very severe dementia. METHODS: We merged palliative
      care consultation data in 31 NHs in two states to Medicare data to identify
      residents with consultations, moderate-to-very severe dementia, and deaths in
      2006-2010. Initial palliative consultations were identified as occurring later
      and earlier (1-30 days and 31-180 days before death, respectively). Three
      controls for each consultation recipient were selected using propensity score
      matching. Weighted multivariate analyses evaluated the effect of consultations on
      hospital or acute care use seven and 30 days before death and on (potentially)
      burdensome transitions (i.e., hospital or hospice admission three days before
      death or two plus acute care transitions 30 days before death). RESULTS: With
      earlier consultation (vs. no consultation), hospitalization rates in the seven
      days before death were on average 13.2 percentage points lower (95% confidence
      interval [CI] -21.8%, -4.7%) and with later consultation 5.9 percentage points
      lower (95% CI -13.7%, +4.9%). For earlier consultations (vs. no consultations),
      rates were 18.4 percentage points lower (95% CI -28.5%, -8.4%) for
      hospitalizations and 11.9 lower (95% CI -20.7%, -3.1%) for emergency room visits
      30 days before death; they were 20.2 percentage points lower (95% CI -28.5%, 
      12.0%) for burdensome transitions. CONCLUSION: Consultations appear to reduce
      acute care use and (potentially) burdensome transitions for dying residents with
      dementia. Reductions were greater when consultations were earlier.

PMID- 28438591
TI  - Effect of anesthesia on intraocular pressure measurement in children.
AB  - Measurement of the intraocular pressure (IOP) is central to the diagnosis and
      management of pediatric glaucoma. An examination under anesthesia is often
      necessary in pediatric patients. Different agents used for sedation or general
      anesthesia have varied effects on IOP. Hemodynamic factors, methods of airway
      management, tonometry technique, and body positioning can all affect IOP
      measurements. The most accurate technique is one that reflects the awake IOP. We
      review factors affecting IOP measurements in the pediatric population and provide
      recommendations on the most accurate means to measure IOP under anesthesia based
      on the present literature.

PMID- 28438592
TI  - AGA Educational Tools Engage Patients and Can Improve Patient Conversations.

PMID- 28438593
TI  - Re: The development of a shoulder specific left/right judgement task: Validity &
      reliability.

PMID- 28438594
TI  - Musculoskeletal science & practice and social media.

PMID- 28438595
TI  - Does Administration of Oral Versus Intravenous Antibiotics for Third Molar
      Removal Have an Effect on the Incidence of Alveolar Osteitis or Postoperative
      Surgical Site Infections?
AB  - PURPOSE: To compare the incidence of postoperative alveolar osteitis (AO) and
      surgical site infections (SSIs) in 2 separate cohorts of patients undergoing
      elective third molar removal: those who received postoperative oral (PO)
      antibiotics and those who received perioperative intravenous (IV) antibiotics.
      MATERIALS AND METHODS: A retrospective cohort study of all patients 14 to 30
      years old undergoing elective outpatient third molar removal under a single
      surgeon's service over a 12-year period was completed. Patients undergoing third
      molar removal during the first 72 months received postoperative PO antibiotics
      alone. Patients undergoing third molar removal during the second 72 months
      received perioperative IV antibiotics alone. The primary predictor variable for
      the study was the antibiotic regimen used at the time of third molar removal. The
      primary outcome variable was the postoperative development of AO or SSI.
      Covariates included age and gender. Univariable and multivariable regression
      models assessed for associations between the antibiotic regimen used and the
      presence of AO and SSI. RESULTS: The study sample consisted of 1,895 patients
      (1,020 patients receiving postoperative PO antibiotics and 875 patients receiving
      perioperative IV antibiotics). Of patients receiving postoperative PO
      antibiotics, 6.4% developed AO an average of 5.7 days after the procedure and
      2.6% developed an SSI an average of 23.2 days after the procedure. Of patients
      receiving perioperative IV antibiotics, 5.5% developed AO an average of 6.2 days
      after the procedure and 3.3% developed an SSI an average of 18.2 days after the
      procedure. No statistically significant associations between the antibiotic
      regimen used and the presence of AO or SSI were identified in univariable (P =
      0.42 for AO, P = 0.32 for SSI) or multivariable (P = 0.65 for AO, P = 0.26 for
      SSI) analyses. In the postoperative PO antibiotic cohort, older age (P < .001)
      and female gender (P < .001) were significantly associated with the development
      of AO, and female gender (P = .015) was significantly associated with the
      presence of an SSI. In the perioperative IV antibiotic cohort, female gender was
      significantly associated with the development of AO (P = .011), and younger age
      was significantly associated with the presence of an SSI (P = .011). CONCLUSION:
      The use of a postoperative PO versus a perioperative IV antibiotic regimen does
      not significantly alter the incidence of AO or SSI after elective third molar
      removal. If the surgeon chooses to use antibiotics in the setting of third molar
      surgery, then perioperative IV antibiotics are preferable over postoperative PO
      antibiotics because they obviate any issues with patient compliance and might be
      less costly.

PMID- 28438596
TI  - Can Preoperative Intramuscular Single-Dose Dexamethasone Improve Patient-Centered
      Outcomes Following Third Molar Surgery?
AB  - PURPOSE: Because of increased attention focused on administering dexamethasone to
      treat third molar surgical complications, this study investigated the efficacy of
      single-dose dexamethasone in managing postoperative complications after impacted
      third molar surgery. Pain intensity and analgesic intake, patients' discomfort,
      limitation of oral function, and limitation of daily activities were assessed.
      MATERIALS AND METHODS: This triple-blinded split-mouth randomized controlled
      clinical trial included patients 18 to 30 years old who underwent randomized
      bilateral extractions of impacted mandibular third molars during 2 consecutive
      sessions. Each patient was given a single-dose intramuscular injection of
      dexamethasone (0.1 mg/kg) preoperatively in 1 session and a placebo in the other
      session. Data were collected daily for 7 postoperative days, and 14 patient
      centered outcomes were interpreted. A 2-tailed P value less than .05 was
      considered significant. RESULTS: All 32 patients (100%) enrolled completed the
      study. When administered dexamethasone, patients reported less pain (P <= .007),
      took fewer analgesics (P <= .002), reported less swelling (P <= .007), had less
      difficulty in eating (P <= .024), had less difficulty in enjoying food (P <=
      .005), had less difficulty in speech (P = .043), had less trismus (P = .005),
      were absent less from school or work (P <= .016), and had less disruption of
      daily activity (P <= .042). The differences between the 2 conditions in bleeding,
      malaise, and sleep disturbance were not significant (P > .05). CONCLUSION:
      Prophylactic dexamethasone administered intramuscularly before third molar
      surgery should be recommended as a safe and effective strategy for decreasing
      pain and discomfort and enhancing oral functions and daily activities, unless
      contraindicated.

PMID- 28438597
TI  - Massive Middle Cerebral Artery Infarction After Surgically Assisted Rapid Palatal
      Expansion: A Case Report.
AB  - Dentofacial deformities have a marked impact on a patient's quality of life.
      Fortunately, these deformities often can be corrected through orthodontic and
      surgical treatment. In adults, transverse maxillary discrepancies are often
      corrected by performing a surgically assisted rapid palatal expansion (SARPE)
      procedure. This procedure is accompanied by many of the same complications
      involved in performing a Le Fort I osteotomy. Although major complications from
      maxillary surgery are uncommon, severe hemorrhage and cerebrovascular accidents
      are real risks accompanied by serious sequelae. The purpose of this case report
      is to describe a case in which a patient developed a massive middle cerebral
      artery infarct after a SARPE procedure. The authors discuss the possible etiology
      and pathogenesis of the complication. They also aim to remind surgeons of this
      rare complication to ensure prompt recognition and management to prevent delays
      in care.

PMID- 28438598
TI  - Effectiveness of Corticoid Administration in Orthognathic Surgery for Edema and
      Neurosensorial Disturbance: A Systematic Literature Review.
AB  - PURPOSE: The aim of this systematic review was to evaluate the effect of
      corticosteroid (CS) administration on edema and neural regeneration in
      orthognathic surgery. MATERIALS AND METHODS: A systematic literature search was
      conducted using the PubMed (Medline), Cochrane Library, and Scopus databases. The
      PICO approach was used, in which patients with skeletal dentofacial deformity
      composed the population; uni- or bimaxillary orthognathic surgery composed the
      intervention; administration versus no administration of CSs composed the
      comparison; and decrease in postoperative edema and neurosensory disorders
      composed the outcome. Thirty of 240 articles were selected and evaluated for
      their titles and abstracts in relation to the inclusion and exclusion criteria.
      After duplicate references were eliminated, 8 articles remained. RESULTS:
      Patients who used CSs had lower rates of edema. In fact, after 4 months, there
      were no remarkable edema rates. These results suggest that neurosensory disorders
      resolved after 3 months. In addition, in the early and late periods,
      administration of CSs did not influence the regression of neurosensory disorders.
      CONCLUSIONS: Administering CSs in orthognathic surgery improved the regression of
      facial edema independent of the dosage used but did not influence neurosensory
      disorders.

PMID- 28438599
TI  - Newly identified invertebrate-type lysozyme (Splys-i) in mud crab (Scylla
      paramamosain) exhibiting muramidase-deficient antimicrobial activity.
AB  - Lysozymes are widely distributed immune effectors exerting muramidase activity
      against the peptidoglycan of the bacterial cell wall to trigger cell lysis.
      However, some invertebrate-type (i-type) lysozymes deficient of muramidase
      activity still exhibit antimicrobial activity. To date, the mechanism underlying
      the antimicrobial effect of muramidase-deficient i-type lysozymes remains
      unclear. Accordingly, this study characterized a novel i-type lysozyme, Splys-i,
      in the mud crab Scylla paramamosain. Splys-i shared the highest identity with the
      Litopenaeus vannamei i-type lysozyme (Lvlys-i2, 54% identity) at the amino acid
      level. Alignment analysis and 3D structure comparison show that Splys-i may be a
      muramidase-deficient i-type lysozyme because it lacks the two conserved catalytic
      residues (Glu and Asp) that are necessary for muramidase activity. Splys-i is
      mainly distributed in the intestine, stomach, gills, hepatopancreas, and
      hemocytes, and it is upregulated by Vibrio harveyi or Staphylococcus aureus
      challenge. Recombinant Splys-i protein (rSplys-i) can inhibit the growth of Gram
      negative bacteria (V. harveyi, Vibrio alginolyticus, Vibrio parahemolyticus, and
      Escherichia coli), Gram-positive bacteria (S. aureus, Bacillus subtilis, and
      Bacillus megaterium), and the fungus Candida albicans to varying degrees. In this
      study, two binding assays and a bacterial agglutination assay were conducted to
      elucidate the potential antimicrobial mechanisms of Splys-i. Results demonstrated
      that rSplys-i could bind to all nine aforementioned microorganisms. It also
      exhibited a strong binding activity to lipopolysaccharide from E. coli and
      lipoteichoic acid and peptidoglycan (PGN) from S. aureus but a weak binding
      activity to PGN from B. subtilis and beta-glucan from fungi. Moreover, rSplys-i
      could agglutinate these nine types of microorganisms in the presence of Ca2+ at
      different protein concentrations. These results suggest that the binding activity
      and its triggered agglutinating activity might be two major mechanisms of action
      to realize the muramidase-deficient antibacterial activity. In addition, rSplys-i
      can hydrolyze the peptidoglycan of some Gram-positive bacteria because it
      exhibits weak isopeptidase activities in salt and protein concentration-dependent
      manner. This result indicates that such an isopeptidase activity may contribute
      to the muramidase-deficient antimicrobial activity to a certain degree. In
      conclusion, Splys-i is upregulated by pathogenic bacteria, and it inhibits
      bacterial growth by binding and agglutination activities as well as isopeptidase
      activity, suggesting that Splys-i is involved in immune defense against bacteria
      through several different mechanisms of action.

PMID- 28438600
TI  - Neurotrophin receptors in the pathogenesis, diagnosis and therapy of
      neurodegenerative diseases.
AB  - In the last few years, exciting properties have emerged regarding the activation,
      signaling, mechanisms of action, and therapeutic targeting of the two types of
      neurotrophin receptors: the p75NTR with its intracellular and extracellular
      peptides, the Trks, their precursors and their complexes. This review summarizes
      these new developments, with particular focus on neurodegenerative diseases.
      Based on the evolving knowledge, innovative concepts have been formulated
      regarding the pathogenesis of these diseases, especially the Alzheimer's and two
      other, the Parkinson's and Huntington's diseases. The medical progresses include
      original procedures of diagnosis, started from studies in mice and now
      investigated for human application, based on innovative classes of receptor
      agonists and blockers. In parallel, comprehensive studies have been and are being
      carried out for the development of drugs. The relevance of these studies is based
      on the limitations of the therapies employed until recently, especially for the
      treatment of Alzheimer's patients. Starting from well known drugs, previously
      employed for non-neurodegenerative diseases, the ongoing progress has lead to the
      development of small molecules that cross rapidly the blood-brain barrier. Among
      these molecules the most promising are specific blockers of the p75NTR receptor.
      Additional drugs, that activate Trk receptors, were shown effective against
      synaptic loss and memory deficits. In the near future such approaches,
      coordinated with treatments with monoclonal antibodies and with developments in
      the microRNA field, are expected to improve the therapy of neurodegenerative
      diseases, and may be relevant also for other human disease conditions.

PMID- 28438601
TI  - Who and how in the regulation of mitochondrial cristae shape and function.
AB  - Mitochondrial adaptation to different physiological conditions highly relies on
      the regulation of mitochondrial ultrastructure, particularly at the level of
      cristae compartment. Cristae represent the membrane hub where most of the
      respiratory complexes embed to account for OXPHOS and energy production in the
      form of adenosine triphosphate (ATP). Changes in cristae number and shape define
      the respiratory capacity as well as cell viability. The identification of key
      regulators of cristae morphology and the understanding of their contribution to
      the mitochondrial ultrastructure and function have become an strategic goal to
      understand mitochondrial disorders and to exploit as therapeutic targets. This
      review summarizes the known regulators of cristae ultrastructure and discusses
      their contribution and implications for mitochondrial dysfunction.

PMID- 28438602
TI  - Hyperoxia exposure disrupts adrenomedullin signaling in newborn mice:
      Implications for lung development in premature infants.
AB  - Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD), a
      chronic lung disease of human infants that is characterized by disrupted lung
      angiogenesis. Adrenomedullin (AM) is a multifunctional peptide with angiogenic
      and vasoprotective properties. AM signals via its cognate receptors, calcitonin
      receptor-like receptor (Calcrl) and receptor activity-modifying protein 2
      (RAMP2). Whether hyperoxia affects the pulmonary AM signaling pathway in neonatal
      mice and whether AM promotes lung angiogenesis in human infants are unknown.
      Therefore, we tested the following hypotheses: (1) hyperoxia exposure will
      disrupt AM signaling during the lung development period in neonatal mice; and (2)
      AM will promote angiogenesis in fetal human pulmonary artery endothelial cells
      (HPAECs) via extracellular signal-regulated kinases (ERK) 1/2 activation. We
      initially determined AM, Calcrl, and RAMP2 mRNA levels in mouse lungs on
      postnatal days (PND) 3, 7, 14, and 28. Next we determined the mRNA expression of
      these genes in neonatal mice exposed to hyperoxia (70% O2) for up to 14 d.
      Finally, using HPAECs, we evaluated if AM activates ERK1/2 and promotes tubule
      formation and cell migration. Lung AM, Calcrl, and RAMP2 mRNA expression
      increased from PND 3 and peaked at PND 14, a time period during which lung
      development occurs in mice. Interestingly, hyperoxia exposure blunted this peak
      expression in neonatal mice. In HPAECs, AM activated ERK1/2 and promoted tubule
      formation and cell migration. These findings support our hypotheses, emphasizing
      that AM signaling axis is a potential therapeutic target for human infants with
      BPD.

PMID- 28438603
TI  - PP2A catalytic subunit silence by microRNA-429 activates AMPK and protects
      osteoblastic cells from dexamethasone.
AB  - Activation of AMP-activated protein kinase (AMPK) could efficiently protect
      osteoblasts from dexamethasone (Dex). Here, we aim to induce AMPK activation
      through miRNA-mediated downregulating its phosphatase, protein phosphatase 2A
      (PP2A). We discovered that microRNA-429 ("miR-429") targets the catalytic subunit
      of PP2A (PP2A-c). Significantly, expression of miR-429 downregulated PP2A-c and
      activated AMPK (p-AMPKalpha1 Thr172) in human osteoblastic cells (OB-6 and
      hFOB1.19 lines). Remarkably, miR-429 expression alleviated Dex-induced
      osteoblastic cell death and apoptosis. On the other hand, miR-429-induced AMPK
      activation and osteoblast cytoprotection were almost abolished when AMPKalpha1
      was either silenced (by targeted shRNA) or mutated (T172A inactivation). Further
      studies showed that miR-429 expression in osteoblastic cells increased NADPH
      (nicotinamide adenine dinucleotide phosphate) content to significantly inhibit
      Dex-induced oxidative stress. Such effect by miR-429 was again abolished with
      AMPKalpha1 silence or mutation. Together, we propose that PP2A-c silence by miR
      429 activates AMPK and protects osteoblastic cells from Dex.

PMID- 28438604
TI  - First reported Chinese case of guanidinoacetate methyltransferase deficiency in a
      4-year-old child.
AB  - Guanidinoacetate methyltransferase (GAMT) deficiency is a rare inherited disorder
      characterized by creatine (Cr) depletion and guanidinoacetate (GAA) accumulation
      in body fluids. We report the first identified Chinese case, diagnosed in a 4
      year-old girl with onset of global developmental. Low Cr and high GAA levels were
      detected in her serum and urine, and low Cr level in her brain. Compound
      heterozygous variants in GAMT gene were found, including a previously reported
      variant at c.491dupG which was inherited from her mother and a novel variant at
      c.564G>T, which was inherited from her father. The Cr and GAA levels returned
      back to normal after 3 months of treatment. After one year of treatment, the
      patient stopped taking antiepileptic drugs and her electroencephalogram (EEG) was
      also back to normal. The girl was followed up for five years and exhibited good
      results beyond our expectation. The results have shown that protein restriction
      with high-dose ornithine and creatine supplements have strong therapeutic
      potential for our patient.

PMID- 28438605
TI  - Identifying Barriers to Delivering the Awakening and Breathing Coordination,
      Delirium, and Early Exercise/Mobility Bundle to Minimize Adverse Outcomes for
      Mechanically Ventilated Patients: A Systematic Review.
AB  - BACKGROUND: Improved outcomes are associated with the Awakening and Breathing
      Coordination, Delirium, and Early exercise/mobility bundle (ABCDE); however,
      implementation issues are common. As yet, no study has integrated the barriers to
      ABCDE to provide an overview of reasons for less successful efforts. The purpose
      of this review was to identify and catalog the barriers to ABCDE delivery based
      on a widely used implementation framework, and to provide a resource to guide
      clinicians in overcoming barriers to implementation. METHODS: We searched MEDLINE
      via PubMed, CINAHL, and Scopus for original research articles from January 1,
      2007, to August 31, 2016, that identified barriers to ABCDE implementation for
      adult patients in the ICU. Two reviewers independently reviewed studies,
      extracted barriers, and conducted thematic content analysis of the barriers,
      guided by the Consolidated Framework for Implementation Research. Discrepancies
      were discussed, and consensus was achieved. RESULTS: Our electronic search
      yielded 1,908 articles. After applying our inclusion/exclusion criteria, we
      included 49 studies. We conducted thematic content analysis of the 107 barriers
      and identified four classes of ABCDE barriers: (1) patient-related (ie, patient
      instability and safety concerns); (2) clinician-related (ie, lack of knowledge,
      staff safety concerns); (3) protocol-related (ie, unclear protocol criteria,
      cumbersome protocols to use); and, not previously identified in past reviews, (4)
      ICU contextual barriers (ie, interprofessional team care coordination).
      CONCLUSIONS: We provide the first, to our knowledge, systematic differential
      diagnosis of barriers to ABCDE delivery, moving beyond the conventional focus on
      patient-level factors. Our analysis offers a differential diagnosis checklist for
      clinicians planning ABCDE implementation to improve patient care and outcomes.

PMID- 28438607
TI  - Obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an
      inability to activate mitophagy.
AB  - Mitochondria are the most prominent organelle in the oocyte. Somatic cells
      maintain a healthy population of mitochondria by degrading damaged mitochondria
      via mitophagy, a specialized autophagy pathway. However, evidence from previous
      work investigating the more general macroautophagy pathway in oocytes suggests
      that mitophagy may not be active in the oocyte. This would leave the vast numbers
      of mitochondria - poised to be inherited by the offspring - vulnerable to damage.
      Here we test the hypothesis that inactive mitophagy in the oocyte underlies
      maternal transmission of dysfunctional mitochondria. To determine whether oocytes
      can complete mitophagy, we used either CCCP or AntimycinA to depolarize
      mitochondria and trigger mitophagy. After depolarization, we did not detect co
      localization of mitochondria with autophagosomes and mitochondrial DNA copy
      number remained unchanged, indicating the non-functional mitochondrial population
      was not removed. To investigate the impact of an absence of mitophagy in oocytes
      with damaged mitochondria on offspring mitochondrial function, we utilized in
      vitro fertilization of high fat high sugar (HF/HS)-exposed oocytes, which have
      lower mitochondrial membrane potential and damaged mitochondria. Here, we
      demonstrate that blastocysts generated from HF/HS oocytes have decreased
      mitochondrial membrane potential, lower metabolites involved in ATP generation,
      and accumulation of PINK1, a mitophagy marker protein. This mitochondrial
      phenotype in the blastocyst mirrors the phenotype we show in HF/HS exposed
      oocytes. Taken together, these data suggest that the mechanisms governing oocyte
      mitophagy are fundamentally distinct from those governing somatic cell mitophagy
      and that the absence of mitophagy in the setting of HF/HS exposure contributes to
      the oocyte-to-blastocyst transmission of dysfunctional mitochondria.

PMID- 28438606
TI  - Cell origin, volume and arrangement are drivers of articular cartilage formation,
      morphogenesis and response to injury in mouse limbs.
AB  - Limb synovial joints are composed of distinct tissues, but it is unclear which
      progenitors produce those tissues and how articular cartilage acquires its
      functional postnatal organization characterized by chondrocyte columns, zone
      specific cell volumes and anisotropic matrix. Using novel Gdf5CreERT2 (Gdf5-CE),
      Prg4-CE and Dkk3-CE mice mated to R26-Confetti or single-color reporters, we
      found that knee joint progenitors produced small non-migratory progenies and
      distinct local tissues over prenatal and postnatal time. Stereological imaging
      and quantification indicated that the columns present in juvenile-adult tibial
      articular cartilage consisted of non-daughter, partially overlapping lineage
      cells, likely reflecting cell rearrangement and stacking. Zone-specific increases
      in cell volume were major drivers of tissue thickening, while cell proliferation
      or death played minor roles. Second harmonic generation with 2-photon microscopy
      showed that the collagen matrix went from being isotropic and scattered at young
      stages to being anisotropic and aligned along the cell stacks in adults.
      Progenitor tracing at prenatal or juvenile stages showed that joint injury
      provoked a massive and rapid increase in synovial Prg4+ and CD44+/P75+ cells some
      of which filling the injury site, while neighboring chondrocytes appeared
      unresponsive. Our data indicate that local cell populations produce distinct
      joint tissues and that articular cartilage growth and zonal organization are
      mainly brought about by cell volume expansion and topographical cell
      rearrangement. Synovial Prg4+ lineage progenitors are exquisitely responsive to
      acute injury and may represent pioneers in joint tissue repair.

PMID- 28438608
TI  - Serological evidence of hepatitis E virus infection in dromedary camels in
      Ethiopia.
AB  - The genome of dromedary camel hepatitis E virus (DcHEV) has been detected in
      stool and serum samples from dromedary camels, but the sero-epidemiological
      information of DcHEV infection remains unclear. A total of 246 serum samples
      collected from dromedary camels (Camelus dromedarius) in Ethiopia, and 40 serum
      samples from Bactrian camels (Camelus ferus) in Mongolia were examined for the
      detection of anti-DcHEV IgG antibody by a newly developed enzyme-linked
      immunosorbent assay (ELISA) by using DcHEV-like particles (DcHEV-LPs) as the
      antigen. The results revealed that 55 of the 246 (22.4%) dromedary camels were
      positive for anti-DcHEV IgG, whereas all 40 samples from the Bactrian camels were
      negative for DcHEV IgG antibody. A total of 98 serum samples from dromedary
      camels, including 25 anti-DcHEV-IgG positive samples, were used for the detection
      of DcHEV RNA by reverse transcription-polymerase chain reaction (RT-PCR),
      however, no positive samples were identified. These results suggested that the
      DcHEV infection occurred in the dromedary camels in Ethiopia. Further studies are
      required to determine whether Bactrian camels are susceptible to DcHEV infection.
      In addition, not only DcHEV-LPs, but also virus-like particles (VLPs) delivered
      from G1, G3 and G5 HEV are likely applicable for the detection of the anti-DcHEV
      IgG antibody.

PMID- 28438609
TI  - Novel replicons and trans-encapsidation systems for Hepatitis C Virus proteins
      live imaging and virus-host interaction proteomics.
AB  - Proteomics and imaging techniques are used more and more in tandem to investigate
      the virus-host interaction. Herein we present novel replicons, methods and trans
      encapsidation systems suitable for determination of Hepatitis C Virus (HCV)
      proteins interactomes and live imaging of viral proteins dynamics in HCV cell
      culture (HCVcc) system. To identify endogenous factors involved in the HCV life
      cycle, we constructed full-length functional replicons with affinity purification
      (AP) tags fused to NS2 and NS5A proteins. Viral-host interactomes were determined
      and validated in HCVcc system. To investigate the dynamics of viral-host
      interactions, we developed a core-inducible packaging cell line which trans
      encapsidates various subgenomic replicons suitable for AP in replication and
      assembly stages. Further, a transient trans-encapsidation system was developed
      for live imaging of the NS5A viral protein in replication and assembly steps,
      respectively. The NS5A dynamics was determined also in the full-length HCV
      replicon system. The analysis of NS5A dynamics showed a decreased mobility of the
      protein in assembly versus the replication step. The tools presented herein will
      allow the investigation of HCV-host interaction with improved biological
      relevance and biosafety.

PMID- 28438612
TI  - Glucose and glutamine in the mitochondrial oxidative metabolism of stem cells.

PMID- 28438610
TI  - Hyperglycemia Increases Interstitial Cells of Cajal via MAPK1 and MAPK3 Signaling
      to ETV1 and KIT, Leading to Rapid Gastric Emptying.
AB  - BACKGROUND & AIMS: Depletion of interstitial cells of Cajal (ICCs) is common in
      diabetic gastroparesis. However, in approximately 20% of patients with diabetes,
      gastric emptying (GE) is accelerated. GE also occurs faster in obese individuals,
      and is associated with increased blood levels of glucose in patients with type 2
      diabetes. To understand the fate of ICCs in hyperinsulinemic, hyperglycemic
      states characterized by rapid GE, we studied mice with mutation of the leptin
      receptor (Leprdb/db), which in our colony had accelerated GE. We also
      investigated hyperglycemia-induced signaling in the ICC lineage and ICC
      dependence on glucose oxidative metabolism in mice with disruption of the
      succinate dehydrogenase complex, subunit C gene (Sdhc). METHODS: Mice were given
      breath tests to analyze GE of solids. ICCs were studied by flow cytometry,
      intracellular electrophysiology, isometric contractility measurement, reverse
      transcription polymerase chain reaction, immunoblot, immunohistochemistry, enzyme
      linked immunosorbent assays, and metabolite assays; cells and tissues were
      manipulated pharmacologically and by RNA interference. Viable cell counts,
      proliferation, and apoptosis were determined by methyltetrazolium, Ki-67,
      proliferating cell nuclear antigen, bromodeoxyuridine, and caspase-Glo 3/7
      assays. Sdhc was disrupted in 2 different strains of mice via cre recombinase.
      RESULTS: In obese, hyperglycemic, hyperinsulinemic female Leprdb/db mice, GE was
      accelerated and gastric ICC and phasic cholinergic responses were increased.
      Female KitK641E/+ mice, which have genetically induced hyperplasia of ICCs, also
      had accelerated GE. In isolated cells of the ICC lineage and gastric organotypic
      cultures, hyperglycemia stimulated proliferation by mitogen-activated protein
      kinase 1 (MAPK1)- and MAPK3-dependent stabilization of ets variant 1-a master
      transcription factor for ICCs-and consequent up-regulation of v-kit Hardy
      Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) receptor tyrosine kinase.
      Opposite changes occurred in mice with disruption of Sdhc. CONCLUSIONS:
      Hyperglycemia increases ICCs via oxidative metabolism-dependent, MAPK1- and MAPK3
      mediated stabilization of ets variant 1 and increased expression of KIT, causing
      rapid GE. Increases in ICCs might contribute to the acceleration in GE observed
      in some patients with diabetes.

PMID- 28438611
TI  - Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal
      Absorption of Cholesterol in Adult Mice.
AB  - In nematodes, the intestine senses and integrates early life dietary cues that
      lead to lifelong epigenetic adaptations to a perceived nutritional environment-it
      is not clear whether this process occurs in mammals. We aimed to establish a
      mouse model of reduced dietary cholesterol availability from maternal milk and
      investigate the consequences of decreased milk cholesterol availability, early in
      life, on the metabolism of cholesterol in adult mice. We blocked intestinal
      absorption of cholesterol in milk fed to newborn mice by supplementing the food
      of dams (for 3 weeks between birth and weaning) with ezetimibe, which is secreted
      into milk. Ezetimibe interacts with the intestinal cholesterol absorption
      transporter NPC1l1 to block cholesterol uptake into enterocytes. Characterization
      of these offspring at 24 weeks of age showed a 27% decrease in cholesterol
      absorption (P < .001) and reduced levels of Npc1l1 messenger RNA and protein, but
      not other cholesterol transporters, in the proximal small intestine. We observed
      increased histone H3K9me3 methylation at positions -423 to -607 of the proximal
      Npc1l1 promoter in small intestine tissues from 24-week-old offspring fed
      ezetimibe during lactation, compared with controls. These findings show that the
      early postnatal mammalian intestine functions as an environmental sensor of
      nutritional conditions, responding to conditions such as low cholesterol levels
      by epigenetic modifications of genes. Further studies are needed to determine how
      decreased sterol absorption for a defined period might activate epigenetic
      regulators; the findings of our study might have implications for human infant
      nutrition and understanding and preventing cardiometabolic disease.

PMID- 28438614
TI  - The expression of GHRH and its receptors in breast carcinomas with apocrine
      differentiation-further evidence of the presence of a GHRH pathway in these
      tumors.
AB  - Apocrine breast carcinomas were evaluated for the expression of components of the
      growth hormone-releasing hormone (GHRH) autocrine/paracrine pathway: GHRH and its
      receptors (GHRH-R), as mammary apocrine carcinomas and epithelium seemed to be
      uniformly positive for GHRH-R in a pilot study. The apocrine phenotype was
      determined on the basis of hematoxylin-eosin morphology and a congruent
      immunohistochemical profile (estrogen receptor negativity, androgen receptor and
      gross cystic disease fluid protein-15 positivity). Thirty-five formalin-fixed,
      paraffin-embedded apocrine breast cancers in tissue microarrays and 24 cases
      using whole-tissue sections were evaluated for GHRH-R and GHRH expression by
      immunohistochemistry using polyclonal antibodies raised against various domains
      of GHRH-R and one polyclonal antibody specific for GHRH. GHRH-R positivity was
      detected in the overwhelming majority (ranging from 90% to 100%) of apocrine
      breast carcinomas with all but one of the antibodies applied. The expression was
      usually diffuse with only isolated cases showing positivity in less than 50% of
      tumor cells. With the PA5-33583 antibody, GHRH-R positivity was seen only in 73%
      of the cases in at least 50% of the tumor cells. GHRH expression was also present
      in all but one case tested, with more than 50% of the cells expressing it in
      30/34 cases. These results support a high rate of GHRH-R and GHRH expression in
      apocrine breast carcinomas. Whether these findings can be exploited for the
      targeted treatment of apocrine breast carcinomas with GHRH antagonists requires
      further study.

PMID- 28438613
TI  - Stress-altered synaptic plasticity and DAMP signaling in the hippocampus-PFC
      axis; elucidating the significance of IGF-1/IGF-1R/CaMKIIalpha expression in
      neural changes associated with a prolonged exposure therapy.
AB  - Traumatic stress patients showed significant improvement in behavior after a
      prolonged exposure to an unrelated stimulus. This treatment method attempts to
      promote extinction of the fear memory associated with the initial traumatic
      experience. However, the subsequent prolonged exposure to such stimulus creates
      an additional layer of neural stress. Although the mechanism remains unclear,
      prolonged exposure therapy (PET) likely involves changes in synaptic plasticity,
      neurotransmitter function and inflammation; especially in parts of the brain
      concerned with the formation and retrieval of fear memory (Hippocampus and
      Prefrontal Cortex: PFC). Since certain synaptic proteins are also involved in
      danger-associated molecular pattern signaling (DAMP), we identified the
      significance of IGF-1/IGF-1R/CaMKIIalpha expression as a potential link between
      the concurrent progression of synaptic and inflammatory changes in stress. Thus,
      a comparison between IGF-1/IGF-1R/CaMKIIalpha, synaptic and DAMP proteins in
      stress and PET may highlight the significance of PET on synaptic morphology and
      neuronal inflammatory response. In behaviorally characterized Sprague-Dawley
      rats, there was a significant decline in neural IGF-1 (p<0.001), hippocampal
      (p<0.001) and cortical (p<0.05) IGF-1R expression. These animals showed a
      significant loss of presynaptic markers (synaptophysin; p<0.001), and changes in
      neurotransmitters (VGLUT2, Tyrosine hydroxylase, GABA, ChAT). Furthermore, naive
      stressed rats recorded a significant decrease in post-synaptic marker (PSD-95;
      p<0.01) and synaptic regulator (CaMKIIalpha; p<0.001). As part of the synaptic
      response to a decrease in brain CaMKIIalpha, small ion conductance channel
      (KCa2.2) was upregulated in the brain of naive stressed rats (p<0.01). After a
      PET, an increase in IGF-1 (p<0.05) and IGF-1R was recorded in the Stress-PET
      group (p<0.001). As such, hippocampal (p<0.001), but not cortical (ns)
      synaptophysin expression increased in Stress-PET. Although PSD-95 was relatively
      unchanged in the hippocampus and PFC, CaMKIIalpha (p<0.001) and KCa2.2 (p<0.01)
      were upregulated in Stress-PET, and may be involved in extinction of fear memory
      related synaptic potentials. These changes were also associated with a normalized
      neurotransmitter function, and a significant reduction in open space avoidance;
      when the animals were assessed in elevated plus maze (EPM). In addition to a
      decrease in IGF-1/IGF-1R, an increase in activated hippocampal and cortical
      microglia was seen in stress (p<0.05) and after a PET (Stress-PET; p<0.001).
      Furthermore, this was linked with a significant increase in HMGB1 (Hippocampus:
      p<0.001, PFC: p<0.05) and TLR4 expression (Hippocampus: p<0.01; PFC: ns) in the
      neurons. Taken together, this study showed that traumatic stress and subsequent
      PET involves an event-dependent alteration of IGF1/IGF-1R/CaMKIIalpha. Firstly,
      we showed a direct relationship between IGF-1/IGF-1R expression, presynaptic
      function (synaptophysin) and neurotransmitter activity in stress and PET.
      Secondly, we identified the possible role of CaMKIIalpha in post-synaptic
      function and regulation of small ion conductance channels. Lastly, we highlighted
      some of the possible links between IGF1/IGF-1R/CaMKIIalpha, the expression of
      DAMP proteins, Microglia activation, and its implication on synaptic plasticity
      during stress and PET.

PMID- 28438615
TI  - Clinicopathological, immunohistochemical, and mutational analyses of pulmonary
      enteric adenocarcinoma: usefulness of SATB2 and beta-catenin immunostaining for
      differentiation from metastatic colorectal carcinoma.
AB  - Pulmonary enteric adenocarcinoma (PEA) is a rare variant of pulmonary
      adenocarcinoma; it is sometimes difficult to discriminate between PEA and
      metastatic colorectal carcinoma (MCRC) because of their morphological and
      immunohistochemical resemblance. Here, we conducted clinicopathological,
      immunohistochemical, and mutational analyses of PEA with special focus on its
      differentiation from MCRC. We comparatively analyzed 8 surgically resected PEA
      tumors (7 patients) and 20 cases of MCRC. Patients were aged 43-77 years (average
      age, 64.1 years); 5 of 7 patients were men. Tumor sizes ranged from 1.5 to 11.5
      cm (average size, 4.8 cm). The follow-up period was 1-65 months; 4 patients are
      alive without recurrence, 2 are alive with recurrence, and 1 patient died of
      idiopathic pulmonary fibrosis. Six of the tumors were pure PEA; one PEA tumor had
      a small mucinous adenocarcinoma component; another had a squamous cell carcinoma
      component. Immunohistochemically, the positive rates of PEA for each antibody
      were as follows: CK7, 88% (7/8); CK20, 88% (7/8); TTF-1, 13% (1/8); beta-catenin,
      0% (0/8, strong nuclear expression); and SATB2, 13% (1/8). The positive rates of
      MCRC for these antibodies were 10%, 95%, 5%, 55%, and 100%, respectively. Genetic
      analysis of KRAS, EGFR, and BRAF showed the G12V mutation in exon 2 of KRAS in 1
      PEA. The present study's findings indicate that beta-catenin and SATB2 are useful
      immunohistochemical markers for differentiating between PEA and MCRC.

PMID- 28438616
TI  - Pericytic tumors of the kidney-a clinicopathologic analysis of 17 cases.
AB  - The pericytic (perivascular myoid cell) family of tumors is a distinctive group
      of mesenchymal neoplasms encountered in superficial sites and only rarely seen in
      viscera. The pericytic family subtends a spectrum of lesions, namely, glomus
      tumors and variants; myopericytoma, including myofibroma; and angioleiomyoma. In
      light of the contemporary classification of pericytic lesions, we identified and
      reviewed 17 cases of renal pericytic tumors from the files of 6 referral centers.
      These tumors presented over an age range of 17 to 76 years (mean 46.7, median
      53), with essentially equal male-female ratio. History of hypertension (available
      in 11 patients) was noted in 7 (64%), which persisted even after surgical
      resection, including in 2 younger patients (17 and 30 years). The tumors (1.7
      11.0 cm) included glomus tumors (n=11); glomangiomyoma (n=1); glomus tumor with
      atypical features (n=1); and angioleiomyoma (n=1), as well as tumors showing
      features overlapping pericytic tumor subtypes (n=3). The histomorphology observed
      in these renal examples closely resembled that of their soft tissue counterparts,
      a subset with symplastic changes and atypical features, and pericytic
      immunophenotype. Despite large size and deep site, no progression was identified
      during a median of 7 months follow-up (1-62 months). In context of prior reported
      experience, our series identifies a wide morphologic spectrum, including lesions
      presenting composite morphologies. Taken with the experience of others, our
      series further corroborates that malignant behavior is rare, and that criteria
      associated with aggression among soft tissue pericytic tumors may not be
      predictive for those in the kidney.

PMID- 28438617
TI  - Tumor budding as a risk factor for nodal metastasis in pT1 colorectal cancers: a
      meta-analysis.
AB  - Worldwide, colorectal cancer (CRC) screening programs have significantly
      increased the detection of submucosal (pT1) adenocarcinoma. Completion surgery
      may be indicated after endoscopic excision of these potentially metastasizing
      early cancers. However, the postsurgical prevalence of nodal implants does not
      exceed 15%, leading to questions concerning the clinical appropriateness of any
      post-endoscopy surgery. Eastern scientific societies (Japanese Society for Cancer
      of the Colon-Rectum, in particular) include tumor budding (TB), defined as the
      presence of isolated single cancer cells or clusters of fewer than 5 cancer cells
      at the tumor invasive front, among the variables that must be included in
      histologic reports. In Western countries, however, no authoritative endorsements
      recommend the inclusion of TB in the histology report because of the
      heterogeneity of definitions and measurement methods as well as its apparent poor
      reproducibility. To assess the prognostic value of TB in pT1 CRCs, this meta
      analysis evaluated 41 studies involving a total of 10137 patients. We observed a
      strong association between the presence of TB and risk of nodal metastasis in pT1
      CRC. In comparing TB-positive (684/2401; 28.5%) versus TB-negative (557/7736;
      7.2%) patients, the prevalence of nodal disease resulted in an odds ratio value
      of 6.44 (95% confidence interval, 5.26-7.87; P<.0001; I2 = 30%). This increased
      risk of regional nodal metastasis was further confirmed after accounting for
      potential confounders. These results support the priority of histologically
      reporting TB in any endoscopically removed pT1 CRC to direct more appropriate
      patient management.

PMID- 28438618
TI  - HER2 loss after neoadjuvant treatment: is the adjuvant trastuzumab treatment
      feasible?-reply.

PMID- 28438619
TI  - Implications of infiltrating immune cells within bone marrow of patients with
      diffuse large B-cell lymphoma.
AB  - The implications of infiltrating immune cells, especially T cells and
      macrophages, in the bone marrow (BM) microenvironment of patients with diffuse
      large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate
      the significance of infiltrating immune cells in the BM microenvironment as a
      prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy
      obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells,
      CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and
      interstitial areas of BM by immunohistochemistry and analyzed their
      clinicopathological and prognostic implications. Levels of infiltrating CD3+ T
      cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with
      DLBCL involvement (BMI-positive group) than in that without DLBCL involvement
      (BMI-negative group). Infiltration of CD8+ T cells significantly increased in
      cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level,
      extranodal site involvement >=2 sites, higher Eastern Cooperative Oncology Group
      performance status, and higher International Prognostic Index (IPI) risk. High
      levels of CD3+ T cells were significantly associated with age <=60, and high
      levels of CD163+ macrophages were associated with advanced Ann Arbor stage and
      higher IPI risk. High infiltration of CD8+ T cells was significantly related to
      inferior overall and recurrence-free survival rate, even in the BMI-negative
      group. High infiltration of CD8+ T cells within the pretreatment BM was related
      to poor prognosis, and might be a useful prognostic factor of DLBCL patients.
      Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in
      initial pretreatment BM biopsy of DLBCL patients.

PMID- 28438620
TI  - Expression of protease-activated receptor-2 (PAR-2) is related to advanced
      clinical stage and adverse prognosis in ovarian clear cell carcinoma.
AB  - Recent studies demonstrated that protease-activated receptor-2 (PAR-2) correlates
      with tumor progression in various tissues. On the other hand, oxidative stress
      arising from endometriosis has been considered a cause of carcinogenesis in
      ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative
      stress up-regulates PAR-2 expression, and we conducted the present study to
      investigate the PAR-2 expression and its relation to clinicopathological factors
      and oxidative stress in OCCC. We performed an immunohistochemical evaluation in
      95 cases of OCCC. For the evaluation of oxidative stress markers, 31 cases of
      ovarian endometrioid carcinoma (OEC) were also examined. No significant
      differences in the expression of cyclooxygenase-2 and inducible nitric oxide
      synthase were observed between OCCC and OEC. Sixty-two percent of the OCCC cases
      showed high 8-hydroxydeoxyguanosine expression, whereas all of the OEC cases
      showed almost negative immunoreactivities. The presence of endometriosis did not
      affect the expression of these oxidative stress markers or prognosis. High PAR-2
      expression was observed in 20% (14/71) of the early International Federation of
      Gynecology and Obstetrics (FIGO) stage cases and 58% (14/24) of the advanced FIGO
      stage cases. High PAR-2 expression was significantly correlated with advanced
      FIGO stage and shorter overall survival. We found no correlations between PAR-2
      expression and oxidative stress in OCCC. Our results suggest that PAR-2 plays an
      important role in the progression of OCCC. The expression of 8
      hydroxydeoxyguanosine is a characteristic finding of OCCC, indicating that the
      injury of DNA by oxidative stress may be involved in the carcinogenesis of OCCC.

PMID- 28438621
TI  - HER2 loss after neoadjuvant treatment: is the adjuvant trastuzumab treatment
      feasible?

PMID- 28438622
TI  - p53 alteration in morphologically normal/benign breast luminal cells in BRCA
      carriers with or without history of breast cancer.
AB  - Germline mutations in BRCA genes have been shown to predispose patients to breast
      cancer. Studies have suggested that p53 alteration is a necessary step in
      tumorigenesis in BRCA carriers. Our previous study showed p53 alteration in
      morphologically normal/benign breast luminal cells in sporadic breast cancer
      patients, the so-called breast p53 signature. Here, we studied p53 status in 66
      BRCA1/2 carriers' breasts: 29 patients with breast carcinoma (2 patients with
      bilateral breast carcinomas) and 37 without. Seven of the 12 (58%) triple
      negative breast carcinomas in BRCA carriers were positive for p53 alteration
      (immunohistochemical stain and/or sequencing), the same frequency as in sporadic
      triple-negative breast carcinomas. Focal p53 positivity in adjacent normal/benign
      luminal cells was identified in 4 of the 7 cases with p53-positive carcinomas but
      not in breasts with p53-negative carcinomas, indicating that p53 positivity in
      normal/benign breast luminal cells is not a random event. Furthermore, in BRCA
      carriers' prophylactic mastectomies, 12 of the 94 (12.77%) breasts had focal p53
      positivity in normal/benign luminal cells, with 2 cases in bilateral breasts,
      significantly higher than in previously studied mammoplasty specimens (0%). Our
      study suggests that germline BRCA gene mutations could result in genomic
      instability and an elevated gene mutation rate (such as the p53 gene) in breast
      luminal cells compared with the general population, predisposing BRCA carriers to
      develop p53-positive/triple-negative breast carcinomas.

PMID- 28438623
TI  - EZH2 overexpression in primary gastrointestinal diffuse large B-cell lymphoma and
      its association with the clinicopathological features.
AB  - Gastrointestinal diffuse large B-cell lymphoma (GI DLBCL) is the most common
      gastrointestinal lymphoma. Enhancer of zeste homolog 2 (EZH2) has been implicated
      in the pathogenesis of several cancers. However, EZH2 has not been studied in GI
      DLBCL. Thus, we investigated EZH2 expression and EZH2 Y641 mutation in 100 GI
      DLBCL specimens by immunohistochemistry and sequencing. In addition,
      trimethylated H3K27 (H3K27me3), BCL2, c-MYC, and Ki-67 expression and
      Helicobacter pylori infection were detected, and BCL2 and c-MYC gene
      translocation was assessed. EZH2 was overexpressed in 50% of cases. EZH2
      overexpression was significantly associated with higher stage (P = .014), higher
      International Prognostic Index score (P = .003), reduced overall survival rate (P
      = .030), and H3K27me3 (P = .001) and c-MYC expression (P = .008). We detected
      EZH2 mutations in 1 of 33 (3.0%) DLBCLs with a germinal center immunophenotype.
      The frequency of EZH2 Y641 mutation in GI DLBCL was significantly lower than that
      in patients with DLBCL without gastrointestinal features (P = .022). BCL2 and c
      MYC translocation was detected in 6.5% and 5.1% of cases, respectively. BCL2
      translocation was detected exclusively in the germinal center B-cell-like
      subtype. Chronic gastroenteritis was present in all cases, and 36.4% of gastric
      DLBCL cases had H pylori infection. The data indicate that primary GI DLBCL is
      closely related with chronic inflammation and has a low frequency of molecular
      abnormality, and EZH2 overexpression is significantly associated with inferior
      outcome in patients with primary GI DLBCL; evaluating EZH2 expression has
      therapeutic implications.

PMID- 28438624
TI  - Bladder Recurrence of Clear Cell Sarcoma of the Kidney Seven Years After Initial
      Presentation.
AB  - Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal
      malignancy after Wilms tumor. CCSK has the potential to metastasize to distant
      sites and was historically known as the bone metastasizing renal tumor. We report
      an exceedingly rare case of a bladder recurrence of CCSK. Our patient presented
      with gross hematuria 7 years after initial complete response. He was found to
      have a large sessile bladder tumor and underwent a partial cystectomy with right
      pelvic lymph node dissection. Final pathology was metastatic CCSK.

PMID- 28438625
TI  - Laser Endopyelotomy in the Management of Pelviureteric Junction Obstruction in
      Adults: A Systematic Review of the Literature.
AB  - Laser endopyelotomy (LEP) is considered as an option for the treatment of
      pelviureteric junction obstruction in adults. A comprehensive systematic search
      of the published literature was performed to assess the success rate and
      perioperative complications of LEP in the treatment of primary and secondary
      pelviureteric junction obstruction and to identify the factors that may have an
      impact on the success of LEP. The evidence available has significant limitations
      in terms of the heterogeneous study design and the definitions of outcomes. The
      average overall success rate of the pooled data was 75% with a mean follow-up of
      29 months. Complications were predominately minor with an average rate of 12.5%.

PMID- 28438626
TI  - Near-infrared Intraoperative Molecular Imaging Can Identify Metastatic Lymph
      Nodes in Prostate Cancer.
AB  - OBJECTIVE: To propose a novel method to perform indocyanine green (ICG) based
      near-infrared (NIR) fluorescence imaging during pelvic lymph node dissection
      (PLND) for prostate cancer patients with lymph node metastasis (LNM). MATERIALS
      AND METHODS: A prostate cancer cell line PC3 was used to establish xenograft
      model in NOD/SCID mice. After tumor growth, the mice were injected with ICG
      through the tail vein. Xenografts and surrounding tissues were imaged with NIR
      camera 24 hours after intravenous ICG, and tumor-to-background ratios were
      calculated. We then performed a pilot human study to evaluate the role of NIR
      imaging in robotic PLND after systemic ICG in 4 patients with prostate cancer and
      preoperative lymphadenopathy. RESULTS: ICG localized to PC3 xenografts in the
      mice and all xenografts were highly fluorescent compared with surrounding
      tissues, with a median tumor-to-background ratio of 2.85 (interquartile range =
      2.64-3.90). In the human study, intraoperative in vivo NIR imaging identified 3
      of the 4 preoperative lymphadenopathies as fluorescence-positive, and back table
      ex vivo NIR imaging identified all 4 lymphadenopathies as fluorescence-positive.
      All the lymphadenopathies were found to be LNMs by pathologic examination. Two of
      the four cases had additional LNMs, all of which were fluorescence-positive with
      intraoperative in vivo NIR imaging. CONCLUSION: Intravenously administered ICG
      accumulates in prostate cancers in both a murine model and human patients. NIR
      fluorescence based on intravenous ICG may serve as a useful tool to facilitate
      the identification of positive nodes during PLND in patients with higher risk of
      LNMs.

PMID- 28438627
TI  - Atypical Small Acinar Proliferation and High-grade Prostatic Intraepithelial
      Neoplasia in the Era of Multiparametric Magnetic Resonance Imaging: A
      Contemporary Review.
AB  - Multiparametric magnetic resonance imaging (mpMRI) has added to the armamentarium
      for the diagnosis and surveillance for organ-confined prostate cancer. Atypical
      small acinar proliferation and high-grade prostatic intraepithelial neoplasia
      (HGPIN) are premalignant prostatic lesions. The management of such lesions
      remains contentious, and the addition of mpMRI introduces further uncertainty,
      given its ability to pick up indolent lesions and its use in targeted biopsy. We
      aimed to perform a comprehensive review of current evidence regarding atypical
      small acinar proliferation, high-grade prostatic intraepithelial neoplasia, and
      mpMRI to ascertain a consensus for a current management algorithm.

PMID- 28438628
TI  - Diagnostic Accuracy of 64Copper Prostate-specific Membrane Antigen Positron
      Emission Tomography/Computed Tomography for Primary Lymph Node Staging of
      Intermediate- to High-risk Prostate Cancer: Our Preliminary Experience.
AB  - OBJECTIVE: To assess the diagnostic accuracy of 64Copper prostate-specific
      membrane antigen (64Cu-PSMA) positron emission tomography/computed tomography
      (PET/CT) in the primary lymph node (LN) staging of a selected cohort of
      intermediate- to high-risk prostate cancer (PCa) patients. MATERIALS AND METHODS:
      An observational prospective study was performed in 23 patients with intermediate
      to high-risk PCa, who underwent 64Cu-PSMA PET/CT for local and lymph nodal
      staging before laparoscopic radical prostatectomy with an extended pelvic LN
      dissection. The sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) for LN status of 64Cu-PSMA PET/CT were calculated
      using the final pathological findings as reference. Furthermore, we evaluated the
      correlation of intraprostatic tumor extent and grading with 64Cu-PSMA
      intraprostatic distribution. RESULTS: Pathological analysis of LN involvement in
      413 LNs harvested from our study cohort identified a total of 22 LN metastases in
      8 (5%) of the 23 (35%) PCa patients. Imaging-based LN staging in a per-patient
      analysis showed that 64Cu-PSMA PET/CT was positive in 7 of 8 LN-positive patients
      (22%) with a sensitivity of 87.5%, specificity of 100%, PPV of 100%, and NPV of
      93.7%, considering the maximum standardized uptake value (SUVmax) at 4 hours as
      our reference. Receiver operating characteristic curve was characterized by an
      area under the curve of 0.938. A significant positive association was observed
      between SUVmax at 4 hours with Gleason score, index, and cumulative tumor volume.
      CONCLUSION: In our intermediate- to high-risk PCa patients study cohort, we
      showed the high diagnostic accuracy of 64Cu-PSMA PET/CT for primary LN staging
      before radical prostatectomy.

PMID- 28438630
TI  - Identification of anti-viral activity of the cardenolides, Na+/K+-ATPase
      inhibitors, against porcine transmissible gastroenteritis virus.
AB  - A series of naturally occurring cardenolides that exhibit potent anti
      transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST)
      cells has been identified. In an immunofluorescence assay, these cardenolides
      were found to diminish the expressions of TGEV nucleocapsid and spike protein,
      which was used as an indication for viral replication; block TGEV infection
      induced apoptosis and cytopathic effects; and impart the same trend of inhibitory
      activity against Na+/K+-ATPase as for anti-TGEV activity. The viral titer
      inhibition was found to take place in a dose-dependent manner. Knocking down
      expression of Na+/K+-ATPase, the cellular receptor of cardenolides, in ST cells
      was found to significantly impair the susceptibility of ST cells to TGEV
      infectivity. Thus, we have identified Na+/K+-ATPase as an anti-viral drug target
      and its antagonists, cardenolides, a novel class of anti- TGEV agents.

PMID- 28438629
TI  - The Impact of Multiple Prostate Biopsies on Risk for Major Complications
      Following Radical Prostatectomy: A Population-based Cohort Study.
AB  - OBJECTIVE: To evaluate the impact of multiple transrectal ultrasound-guided
      prostate biopsies (TRUS-Bx) before radical prostatectomy (RP) on surgical
      outcomes. MATERIALS AND METHODS: Administrative databases were used to identify
      all patients who had a RP performed in the province of Ontario from April 1,
      2002, to March 31, 2013. TRUS-Bx prior to RP were identified and patients were
      categorized as having one or more than one prior TRUS-Bx. The primary end point
      was a composite index of serious surgical complications. Secondary outcomes
      included oncological interventions, functional-related events, and general health
      service-related outcomes. RESULTS: Among 27,637 patients, 4780 (17.3%) had >=2
      biopsies performed before RP. The proportion of patients who experienced the
      composite end point was similar between those with one TRUS-Bx compared to those
      with >=2 TRUS-Bx (1.05% vs 1.19%, OR 1.14, 95% CI 0.85-1.52). Patients with >=2
      biopsies were more likely to have a perioperative blood transfusion compared to
      patients with only 1 biopsy (15.5% vs 12.8%, OR 1.25, 95% CI 1.15-1.37), while
      readmission rate and 30-day mortality were similar. The need for radiotherapy and
      androgen deprivation therapy within the first year after RP was higher in
      patients with a single biopsy. Patients with multiple TRUS-Bx were more likely to
      require post-RP urodynamic evaluation and bladder neck contracture-related
      interventions but were not at increased odds of surgery for incontinence or
      erectile dysfunction. CONCLUSION: Perioperative outcomes after RP are similar
      between men with single or multiple TRUS-Bx, although multiple TRUS-Bx were
      associated with an increased odds of perioperative blood transfusion.

PMID- 28438631
TI  - In vivo inhibitory activity of andrographolide derivative ADN-9 against liver
      cancer and its mechanisms involved in inhibition of tumor angiogenesis.
AB  - It is well known that liver cancer is a highly aggressive malignancy with poor
      prognosis. Andrographolide (AD), a major bioactive component of Andrographis
      paniculata (Burm. F.), is a potential anti-cancer pharmacophore and the synthesis
      of AD derivatives with better cytotoxicity to cancer cells has attracted
      considerable attentions. In the present study, we evaluated the in vivo
      inhibitory effects of ADN-9, a 15-benzylidene substituted derivative of AD, on
      the growth and metastasis of murine hepatoma H22 using an orthotopic xenograft
      model and a subcutaneous xenograft model, and we further studied the anti
      angiogenic action and the related mechanisms of ADN-9 in vivo and in vitro.
      Importantly, ADN-9 remarkably suppressed the growth and metastasis of both
      orthotopic and subcutaneous xenograft tumors, and the serum AFP level in
      orthotopic hepatoma-bearing mice treated with 100mg/kg ADN-9 (ig.) was decreased
      to the normal level. We also found that ADN-9 showed stronger abilities than AD
      in shrinking tumors, suppressing the invasion and metastasis of H22 cells,
      decreasing the MVD and promoting tumor cell apoptosis in subcutaneous xenograft
      of mice. Additionally, ADN-9 exhibited stronger inhibitory activity than AD
      against the migration and VEGF-induced capillary-like tube formation in HUVECs,
      which was further proved to be associated with attenuating VEGF/VEGFR2/AKT
      signaling pathway. The present research provides the first evidence that a 15
      substituted AD derivative is more promising than the parent compound in
      therapeutic treatment of liver cancer.

PMID- 28438632
TI  - Molecular diagnostic development for begomovirus-betasatellite complexes
      undergoing diversification: A case study.
AB  - At least five begomoviral species that cause leaf curl disease of cotton have
      emerged recently in Asia and Africa, reducing fiber quality and yield. The
      potential for the spread of these viruses to other cotton-vegetable growing
      regions throughout the world is extensive, owing to routine, global transport of
      alternative hosts of the leaf curl viruses, especially ornamentals. The research
      reported here describes the design and validation of polymerase chain reaction
      (PCR) primers undertaken to facilitate molecular detection of the two most
      prevalent leaf curl-associated begomovirus-betasatellite complexes in the Indian
      Subcontinent and Africa, the Cotton leaf curl Kokhran virus-Burewala strain and
      Cotton leaf curl Gezira virus, endemic to Asia and Africa, respectively. Ongoing
      genomic diversification of these begomoviral-satellite complexes was evident
      based on nucleotide sequence alignments, and analysis of single nucleotide
      polymorphisms, both factors that created new challenges for primer design. The
      additional requirement for species and strain-specific, and betasatellite
      specific primer design, imposes further constraints on primer design and
      validation due to the large number of related species and strains extant in 'core
      leaf curl virus complex', now with expanded distribution in south Asia, the
      Pacific region, and Africa-Arabian Peninsula that have relatively highly
      conserved coding and non-coding regions, which precludes much of the genome
      betasatellite sequence when selecting primer 'targets'. Here, PCR primers were
      successfully designed and validated for detection of cloned viral genomes and
      betasatellites for representative 'core leaf curl' strains and species, distant
      relatives, and total DNA isolated from selected plant species. The application of
      molecular diagnostics to screen plant imports prior to export or release from
      ports of entry is expected to greatly reduce the likelihood of exotic leaf curl
      virus introductions that could dramatically affect the production of cotton as
      well as vegetable and ornamental crop hosts.

PMID- 28438633
TI  - Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and
      Interferon-Stimulated Gene Product 15 from Different Species.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East
      respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like
      proteases (PLPs) that have the ability to process the viral polyprotein to
      facilitate RNA replication and antagonize the host innate immune response. The
      latter function involves reversing the post-translational modification of
      cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon
      stimulated gene product 15 (ISG15). Ub is known to be highly conserved among
      eukaryotes, but surprisingly, ISG15 is highly divergent among animals. The
      ramifications of this sequence divergence to the recognition of ISG15 by
      coronavirus PLPs at a structural and biochemical level are poorly understood.
      Therefore, the activity of PLPs from SARS-CoV, MERS-CoV, and mouse hepatitis
      virus was evaluated against seven ISG15s originating from an assortment of animal
      species susceptible, and not, to certain coronavirus infections. Excitingly, our
      kinetic, thermodynamic, and structural analysis revealed an array of different
      preferences among PLPs. Included in these studies is the first insight into a
      coronavirus PLP's interface with ISG15 via SARS-CoV PLpro in complex with the
      principle binding domain of human ISG15 (hISG15) and mouse ISG15s (mISG15s). The
      first X-ray structure of the full-length mISG15 protein is also reported and
      highlights a unique, twisted hinge region of ISG15 that is not conserved in
      hISG15, suggesting a potential role in differential recognition. Taken together,
      this new information provides a structural and biochemical understanding of the
      distinct specificities among coronavirus PLPs observed and addresses a critical
      gap of how PLPs can interact with ISG15s from a wide variety of species.

PMID- 28438634
TI  - Structural Insights into BAF47 and BAF155 Complex Formation.
AB  - Mammalian BAF complexes are a subfamily of SWI/SNF ATP-dependent chromatin
      remodelers that dynamically modulate chromatin structure to regulate fundamental
      cellular processes including gene transcription, cell cycle control, and DNA
      damage response. So far, many distinct BAF complexes have been identified with
      polymorphic assemblies of up to 15 subunits from 29 genes. The evolutionarily
      conserved BRG1/BRM, BAF47, and BAF155/BAF170 form a stable complex that carries
      out essential chromatin remodeling activity and therefore have been regarded as
      the core components of BAF complex. Here, we first confirmed that SWIRM domain of
      BAF155 is responsible for its interaction with BAF47 and then narrowed down the
      SWIRM-binding region in BAF47 to the Repeat 1 (RPT1) domain. We further presented
      the high-resolution crystal structure of SWIRM/RPT1 complex. Extensive
      mutagenesis experiments together with isothermal titration calorimetry and NMR
      titrations were performed to corroborate the interactions observed in crystal
      structure. Overall, we demonstrated that BAF155 SWIRM is a modular domain
      involved in BAF47 interaction, which is functionally distinct from other
      characterized SWIRM domains that possess DNA binding activity.

PMID- 28438635
TI  - Testosterone and cortisol responses in male soccer players: The effect of home
      and away venues.
AB  - The present studies examined the influence of playing venue on psychobiological
      responses in male soccer players. Many studies have demonstrated the existence of
      a home advantage, wherein teams perform better at home than away. A recent focus
      has attempted to explain this advantage from a psychobiological perspective, with
      studies showing hormonal differences with regard to venue, game outcome,
      dominance and perceived stress. Two studies investigated testosterone and
      cortisol responses in relation to home and away venues. In an initial study of 18
      male elite Premier League academy soccer players (age, 17.47, SD, 64), salivary
      cortisol levels were monitored in two competitive matches, both at home and away.
      Higher post-game cortisol levels were observed at home (p=0.002), with the team
      winning all its games. In a second study involving a 12 semi-professional group
      of players (age, 23.17, SD, 3.8), the same post-game cortisol findings at home
      were replicated (p=0.001), with this team losing all its games. No effects were
      observed for testosterone in either study. The results extend earlier research
      findings on the complex relationship which surrounds the psychobiological impact
      on the home advantage. The findings suggest that higher levels of stress are
      experienced by home players in their home matches.

PMID- 28438636
TI  - Identification of chemotaxis operon cheYZA and cheA gene expression under
      stressful conditions in Piscirickettsia salmonis.
AB  - Piscirickettsia salmonis is the etiological agent of piscirickettsiosis, which,
      as the main systemic disease in the Chilean salmon industry, causes significant
      economic losses. This bacterium can produce biofilm as a persistence and survival
      strategy in adverse conditions. In other bacteria, cheA is a key gene for
      modulating the onset of bacterial chemotaxis, as well as having a secondary role
      in biofilm production. Notwithstanding this association, the potential
      relationships between biofilm formation and genes involved in P. salmonis
      chemotaxis are poorly understood. This study aimed to determine P. salmonis cheA
      gene expression when grown in different culture media known to induce biofilm
      production. Piscirickettsia salmonis AUSTRAL-005 produced moderate/high biofilm
      levels after 144 h of incubation in the AUSTRAL-SRS and marine broths. In
      contrast, LF-89 biofilm production was weak/nonexistent in the aforementioned
      broths. Both assessed P. salmonis strains contained the cheYZA operon.
      Additionally, AUSTRAL-005 cheA transcripts increased in both culture media. In
      conclusion, these results suggest potential relationships between biofilm
      formation and genes related to chemotaxis in the fish pathogen P. salmonis.

PMID- 28438637
TI  - Cloning and functional analysis of succinate dehydrogenase gene PsSDHA in
      Phytophthora sojae.
AB  - Succinate dehydrogenase (SDH) is one of the key enzymes of the tricarboxylic acid
      cycle (TCA cycle) and a proven target of fungicides for true fungi. To explore
      the roles of the SDHA gene in Phytophthora sojae, we first cloned PsSDHA to
      construct the PsSDHA silenced expression vector pHAM34-PsSDHA, and then utilized
      PEG to mediate the P. sojae protoplast transformation experiment. Through
      transformation screening, we obtained the silenced mutants A1 and A3, which have
      significant suppressive effect. Further study showed that the hyphae of the
      silenced mutant strains were shorter and more bifurcated; the growth of the
      silenced mutants was clearly inhibited in 10% V8 agar medium containing sodium
      chloride (NaCl), hydrogen peroxide (H2O2) or Congo Red, respectively. The
      pathogenicity of the silenced mutants was significantly reduced compared with the
      wild-type strain and the mock. The results could help us better to understand the
      position and function of SDH in P. sojae and provide a proven target of
      fungicides for the oomycete.

PMID- 28438638
TI  - Adenosine A2A receptor modulates neuroimmune function through Th17/retinoid
      related orphan receptor gamma t (RORgammat) signaling in a BTBR T+ Itpr3tf/J
      mouse model of autism.
AB  - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder
      characterized by abnormal social interactions, repetitive behaviors that impair
      social communication, and circumscribed interests. BTBR T+tf/J (BTBR) inbred mice
      are generally used as a model for ASD, as they show repetitive behaviors and
      social deficits that resemble signs of ADS in humans. Adenosine A2A receptors
      (A2ARs) are considered as potential targets in the treatment of immune,
      inflammatory, and neurodegenerative diseases. In this study, we investigated the
      potential effects of the A2A adenosine receptor (A2AR) antagonist SCH 5826 (SCH)
      and agonist CGS 21680 (CGS) on behavior (self-grooming), hot plate test results,
      and expression levels of IL-17A+, RORgammat+, Foxp3+, and IL-10+ in CD4+ T spleen
      cells in BTBR and C57BL/6 (B6) mice. We also assessed IL-17A, RORgammat, Stat3,
      pStat3, Foxp3, and IL-10 mRNA and protein expression levels in the brain tissue.
      The CGS-treated mice showed a significantly altered self-grooming score and a
      reduced response to the hot plate test. The results further revealed that the SCH
      efficiently increased the IL-17A+ and RORgammat+ expression levels and decreased
      the Foxp3+ and IL-10+ expression levels in CD4+ cells. However, the treatment
      with CGS significantly reversed these effects. In addition, CGS significantly
      decreased the IL-17A, RORgammat, Stat3, and pStat3 levels and increased the Foxp3
      and IL-10 mRNA and protein expression levels as compared with the BTBR control
      and SCH treatments. Our results clearly indicate that the CGS A2AR agonist may
      represent a unique target for future therapeutic strategies for neuroimmune
      dysfunction.

PMID- 28438639
TI  - Targeting Interleukin-17 signalling in cigarette smoke-induced lung disease:
      Mechanistic concepts and therapeutic opportunities.
AB  - It is widely accepted that compromised lung function in chronic obstructive
      pulmonary disease (COPD) is, at least in part, a consequence of persistent airway
      inflammation caused by particles and noxious gases present in cigarette smoke and
      indoor air pollution from burning biomass fuel. Currently, the World Health
      Organization estimates that 80 million people have moderate or severe COPD
      worldwide. While there is a global need for effective medical treatment, current
      therapeutic interventions have shown limited success in preventing disease
      pathology and progression. This is, in large part, due to the complexity and
      heterogeneity of COPD, and an incomplete understanding of the molecular
      mechanisms governing inflammatory processes in individual patients. This review
      discusses recent discoveries related to the pro-inflammatory cytokine interleukin
      (IL)-17A, and its potential role in the pathogenesis of COPD. We propose that an
      intervention strategy targeting IL-17 signalling offers an exciting opportunity
      to mitigate inflammatory processes, and prevent the progression of tissue
      pathologies associated with COPD.

PMID- 28438640
TI  - Neutralizing IL-6 reduces heart injury by decreasing nerve growth factor
      precursor in the heart and hypothalamus during rat cardiopulmonary bypass.
AB  - AIMS: To investigate whether the expression of nerve growth factor precursor
      (proNGF) changes during cardiopulmonary bypass (CPB) and whether neutralizing
      interleukin-6 (IL-6) during CPB has cardiac benefits. MAIN METHODS: Thirty
      patients undergoing CPB were recruited and their serum proNGF and troponin-I
      (TNI) were detected. In addition, rats were divided into three groups: CPB group,
      CPB with cardiac ischemia-reperfusion (IR) group, and a control group. The pre
      CPB standard deviation of N-N intervals (SDNN) and post-CPB SDNN were compared.
      At the end of CPB, nerve peptide Y (NPY), acetylcholinesterase, cell apoptosis,
      and proNGF protein expression were measured in the heart and hypothalamus.
      Another rat cohort undergoing CPB was divided into two groups: an anti-IL-6 group
      with IL-6 antibody and a control group with phosphate buffer solution. At the end
      of CPB, serum hs-troponin-T and cardiac caspases 3 and 9 were detected. NPY and
      proNGF in the heart and hypothalamus were detected. KEY FINDINGS: In patients,
      serum proNGF increased during CPB, and the concentration was positively
      correlated with TNI. In rats, cardiac autonomic nervous function was disturbed
      during CPB. More apoptotic cells and higher levels of proNGF were found in the
      heart and hypothalamus in the CPB groups than in the control groups. Neutralizing
      IL-6 was beneficial to lower cardiac injury by decreasing proNGF and apoptosis.
      SIGNIFICANCE: CPB induced changes in proNGF in the heart and hypothalamus.
      Suppressing inflammation attenuated myocardial apoptosis and autonomic nerve
      function disturbance in CPB rats, likely due in part to regulation of proNGF in
      the heart and hypothalamus.

PMID- 28438641
TI  - Improving therapeutics in anorexia nervosa with tryptophan.
AB  - A growing body of evidence suggests that our diet is an important contributing
      factor in the development, management and prevention of a number of psychiatric
      illnesses. Tryptophan, an essential amino acid, is the sole precursor of
      neurotransmitter 5-hydroxytryptamine (5-HT; serotonin). Administration of
      tryptophan can boost serotonin neurotransmission to produce therapeutically
      important effects in serotonin deficiency disorders. Anorexia nervosa (AN) an
      eating disorder associated with high levels of psychiatric comorbidity including
      psychosis, hyperactivity, depression and anxiety has highest lethality of all
      psychiatric illnesses. Evidence suggests that excessive dieting and food
      restriction can decrease brain tryptophan and serotonin in AN patients to
      precipitate depression, psychosis and hyperactivity. There are currently no FDA
      approved pharmacological treatments available for AN patients; antidepressants
      and antipsychotics, largely used to treat associated psychiatric comorbidities
      are also not very effective. The aim of this non-systematic review article is to
      evaluate and document a potential importance of tryptophan supplementation in
      improving therapeutics in AN patients.

PMID- 28438643
TI  - Convenient PCR method for variable-number tandem-repeat typing of Mycobacterium
      tuberculosis clinical isolates.
AB  - Variable-number tandem-repeat typing for Mycobacterium tuberculosis clinical
      isolates contributes to evidence-based tuberculosis control. However, cumbersome
      PCR procedures for the typing have disturbed routine analyses. We proposed a
      convenient PCR method for the typing using a PCR master mix that provides
      rapidity and long-term stability of the frozen PCR cocktail.

PMID- 28438642
TI  - Diagnostic microarray for 14 water and foodborne pathogens using a flatbed
      scanner.
AB  - Parallel detection approaches are of interest to many researchers interested in
      identifying multiple water and foodborne pathogens simultaneously. Availability
      and cost-effectiveness are two key factors determining the usefulness of such
      approaches for laboratories with limited resources. In this study, we developed
      and validated a high-density microarray for simultaneous screening of 14
      bacterial pathogens using an approach that employs gold labeling with silver
      enhancement (GLS) protocol. In total, 8887 probes (50-mer) were designed using an
      in-house database of virulence and marker genes (VMGs), and synthesized in
      quadruplicate on glass slides using an in-situ synthesis technology. Target VMG
      amplicons were obtained using multiplex polymerase chain reaction (PCR), labeled
      with biotin, and hybridized to the microarray. The signals generated after gold
      deposition and silver enhancement, were quantified using a flatbed scanner having
      2-MUm resolution. Data analysis indicated that reliable presence/absence calls
      could be made, if: i) over four probes were used per gene, ii) the signal-to
      noise ratio (SNR) cutoff was greater than or equal to two, and iii) the positive
      fraction (PF), i.e., number of probes with SNR>=2 for a given VMG was greater
      than 0.75. Hybridization of the array with blind samples resulted in 100% correct
      calls, and no false positive. Because amplicons were obtained by multiplex PCR,
      sensitivity of this method is similar to PCR. This assay is an inexpensive and
      reliable technique for high throughput screening of multiple pathogens.

PMID- 28438644
TI  - Long-term effects of angiotensin-(1-7) on lipid metabolism in the adipose tissue
      and liver.
AB  - The angiotensin (Ang) converting enzyme 2/Ang-(1-7)/Mas axis has been described
      to have a beneficial role on metabolic disorders. In the present study, the use
      of a transgenic rat model that chronically overexpresses Ang-(1-7) enabled us to
      investigate the chronic effects of this peptide on lipid accumulation in the
      liver and adipose tissue. The transgenic group showed a marked tendency toward
      increased expression of peroxisome proliferator-activated receptor-gamma
      (PPARgamma) and decreased lipoprotein lipase (LPL) expression and activity in
      epididymal adipose tissue. We also showed that Mas receptor-knockout mice had
      decreased PPARgamma expression in adipose tissue, accompanied by an increase in
      LPL activity. These results confirm the regulation of adipose tissue LPL activity
      by Ang-(1-7) and suggest that this occurs independent of PPARgamma expression.
      The reduced adiposity index of transgenic rats, due to the effect of Ang-(1-7),
      was accompanied by a decrease in lipogenesis. These findings suggest a direct
      effect of Ang-(1-7) on lipogenesis, independent of the stimulatory effect of
      insulin. Furthermore, the decreased concentration of triacylglycerol in the liver
      of transgenic rats may result from increased activity of cytosolic lipases and
      decreased fatty acid uptake from the adipose tissue, determined from fatty acid
      binding protein expression, and hepatic de novo fatty acid synthesis, evaluated
      by fatty acid synthase expression. The data clearly show that Ang-(1-7) regulates
      lipid metabolism in the adipose tissue and liver.

PMID- 28438645
TI  - Releasing the potential power of terpene synthases by a robust precursor supply
      platform.
AB  - Terpenoids represent the largest family of natural products. Their structural
      diversity is largely due to variable skeletons generated by terpene synthases.
      However, terpene skeletons found in nature are much more than those generated
      from known terpene synthases. Most promiscuous terpene synthases (i.e. those that
      can generate more than one product) have not been comprehensively characterised.
      Here, we first demonstrated that the promiscuous terpene synthases can produce
      more variable terpenoids in vivo by converting precursor polyisoprenoid
      diphosphates of different lengths (C10, C15, C20, C25). To release the synthetic
      potential of these enzymes, we integrated the engineered MVA pathway,
      combinatorial biosynthesis, and point mutagenesis to depict the comprehensive
      product profiles. In total, eight new terpenoids were characterised by NMR and
      three new skeletons were revealed. This work highlights the key role of metabolic
      engineering for natural product discovery.

PMID- 28438646
TI  - Assessment of a Revised Wartime Experiences Scale for Vietnam-Era Women: The
      Health of Vietnam-Era Women's Study (HealthViEWS).
AB  - PURPOSE: Few wartime experiences scales capture unique issues related to women's
      service, address their military roles, or have been validated with women. The
      Women's Wartime Stressor Scale was developed for use with women who served during
      the Vietnam era, primarily as nurses in Vietnam. We revised this measure by
      modifying existing items, adding new items, and revising response formats to
      create a scale less nursing specific and nondeployment specific, and conducted a
      preliminary assessment of the revised scale. METHODS: The Women's Wartime
      Exposure Scale-Revised (WWES-R) was included in a mail survey as part of the U.S.
      Department of Veterans Affairs Health of Vietnam-Era Women's Study (HealthViEWS)
      study. Construct and criterion validity, and internal consistency, were assessed
      with a sample of 4,839 women veterans using exploratory factor analysis, analysis
      of variance, and multiple linear regression. RESULTS: Six wartime experience
      factors consistent with previous research were identified and scales were created
      based on salient item loadings. Compared with women serving in the United States,
      women serving in Vietnam had higher mean scores on all scales, and nurses had
      significantly higher scores on three scales than non-nurses. CONCLUSIONS:
      Evaluation of the WWES-R suggests service and/or deployment location and service
      in a military health care versus a non-health care role may predict women
      veterans' reports of certain wartime experiences. Further psychometric evaluation
      of the WWES-R is recommended with later era veterans and through comparisons to
      other wartime exposure measures.

PMID- 28438647
TI  - Effects of BMS-902483, an alpha7 nicotinic acetylcholine receptor partial
      agonist, on cognition and sensory gating in relation to receptor occupancy in
      rodents.
AB  - The alpha7 nicotinic acetylcholine receptor is thought to play an important role
      in human cognition. Here we describe the in vivo effects of BMS-902483, a
      selective potent alpha7 nicotinic acetylcholine receptor partial agonist, in
      relationship to alpha7 nicotinic acetylcholine receptor occupancy. BMS-902483 has
      low nanomolar affinity for rat and human alpha7 nicotinic acetylcholine receptors
      and elicits currents in cells expressing human or rat alpha7 nicotinic
      acetylcholine receptors that are about 60% of the maximal acetylcholine response.
      BMS-902483 improved 24h novel object recognition memory in mice with a minimal
      effective dose (MED) of 0.1mg/kg and reversed MK-801-induced deficits in a rat
      attentional set-shifting model of executive function with an MED of 3mg/kg.
      Enhancement of novel object recognition was blocked by the silent alpha7
      nicotinic acetylcholine receptor agonist, NS6740, demonstrating that activity of
      BMS-902483 was mediated by alpha7 nicotinic acetylcholine receptors. BMS-902483
      also reversed ketamine-induced deficits in auditory gating in rats, and enhanced
      ex vivo hippocampal long-term potentiation examined 24h after dosing in mice.
      Results from an ex vivo brain homogenate binding assay showed that alpha7
      receptor occupancy ranged from 64% (novel object recognition) to ~90% (set shift
      and gating) at the MED for behavioral and sensory processing effects of BMS
      902483.

PMID- 28438648
TI  - The superoxide dismutase mimetic tempol blunts diabetes-induced upregulation of
      NADPH oxidase and endoplasmic reticulum stress in a rat model of diabetic
      nephropathy.
AB  - Endoplasmic reticulum (ER) stress contributes to progression of diabetic
      nephropathy, which promotes end-stage renal failure in diabetic patients. This
      study was undertaken to investigate the actions of tempol and ramipril,
      pharmacological agents that target the consequences of NADPH oxidase, on diabetic
      nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER
      stress. Male Sprague-Dawley rats were injected intravenously with a single bolus
      of streptozotocin (55mg/kg) to induce type 1 diabetes. An additional age-matched
      group of rats was administered with citrate vehicle as controls. After 4 weeks of
      untreated diabetes, rats received tempol (1.5mM/kg/day subcutaneously, n=8),
      ramipril (1mg/kg/day in drinking water, n=8) or remained untreated for an
      additional 4 weeks (n=7). After 8 weeks of diabetes in total, kidneys were
      collected for histological analysis, gene expression and protein abundance.
      Tempol and ramipril blunted diabetes-induced upregulation of NADPH oxidase
      isoforms (Nox4, Nox2, p47phox), accompanied by an amelioration of diabetes
      induced glomerular injury (podocin, nephrin, Kim-1), tubulo-interstitial fibrosis
      (TGFbeta1, TGFbeta-R2, pSMAD3, alpha-SMA) and pro-inflammatory cytokines
      (TNFalpha, MCP-1, ANX-A1, FPR2) expression. In addition, the diabetes-induced
      renal ER stress, evidenced by increased expression of GRP-78 chaperone and stress
      associated markers ATF4, TRB3, as well as XBP1s, phospho-p38 mitogen-activated
      protein kinase (MAPK) and 3-nitrotyrosination, were all attenuated by tempol and
      ramipril. These observations suggest that antioxidant approaches that blunt NADPH
      upregulation may attenuate diabetic nephropathy, at least in part by negatively
      regulating ER stress and inflammation, and hence ameliorating kidney damage.

PMID- 28438649
TI  - Pathophysiological roles of canstatin on myofibroblasts after myocardial
      infarction in rats.
AB  - Myofibroblasts play an important role during remodeling process after myocardial
      infarction through proliferation, migration, production and degradation of
      extracellular matrix (ECM) and contraction. Canstatin, a 24kDa polypeptide, is
      cleaved from alpha2 chain of type IV collagen, which is a major component of
      basement membrane around cardiomyocytes. We examined the effects of canstatin on
      myofibroblasts isolated from the areas of myocardial infarction. Myocardial
      infarction model was made by ligating left anterior descending artery of Wistar
      rats. Two weeks after the operation, the cells were isolated by an explant method
      and identified as myofibroblasts with immunofluorescence staining. Cell counting
      assay was performed to examine cell proliferation. Boyden chamber assay was
      performed to examine cell migration. Expression and phosphorylation of proteins
      were detected by Western blotting. Collagen gel contraction assay was performed
      to measure cell contractility. Canstatin stimulated proliferation, secretion of
      matrix metalloproteinases, expression of cyclooxygenase (COX)-2, and inhibited
      collagen gel contraction in myofibroblasts. Canstatin increased Akt
      phosphorylation. LY294002, a phosphoinositide-3-kinase/Akt inhibitor, inhibited
      the canstatin-induced proliferation. NS-398, a COX-2 inhibitor, suppressed the
      inhibitory effect of canstatin on collagen gel contraction. Canstatin expression
      in areas of myocardial infarction 2 weeks after surgery decreased. We for the
      first time demonstrate that canstatin is an endogenous bioactive molecule
      regulating the various functions of myofibroblasts after myocardial infarction.
      The decrease of canstatin expression in the maturated areas of myocardial
      infarction might lead to stabilization of scar tissues perhaps in part through
      the reduction of proliferation and ECM degradation as well as the stimulation of
      contractility in myofibroblasts.

PMID- 28438650
TI  - Training Young Neurosurgeons in Open Microsurgical Aneurysm Treatment.

PMID- 28438651
TI  - Rare Intracranial Donut Aneurysm.
AB  - A 30-year-old man was admitted for sudden loss of consciousness. On angio-CT, a
      ring-like vascular formation arising from the anterior communicating artery with
      a low-density center was visualized. This finding was consistent with a giant
      arterial aneurysm presenting with a central thrombus, also called "donut
      aneurysm".

PMID- 28438652
TI  - Assessing the Relevancy of Highly Cited Works in Neurosurgery. Part I: The 100
      Most Relevant Papers in Neurosurgical Journals.
AB  - BACKGROUND: Bibliometric analyses based on total citation count come with many
      limitations, which investigators in other fields have overcome using the average
      number of citations per year since publication. METHOD: The following study is
      presented in 2 parts. In this first part, the 100 most relevant articles in
      neurosurgical journals were identified and ranked by total citations per year
      since publication. We queried the Web of Science database for the 1000 most-cited
      articles in neurosurgical journals. The number of citations per year was
      calculated for these 1000 articles, and the top 100 were identified. RESULTS:
      Among the top 100 most relevant articles, 63 were from the Journal of
      Neurosurgery, 26 from Neurosurgery, 7 from the Journal of Neurology,
      Neurosurgery, and Psychiatry, 3 from Acta Neurochirurgica, and 1 from Surgical
      Neurology. The average year of publication for the 100 most relevant articles is
      1995, compared with 1984 for the list of most-cited articles published by Ponce
      and Lozano in 2010 (P < 0.001). CONCLUSION: These results suggest that ranking
      articles based on relevancy rather than historical popularity results in a list
      of more recently published articles and includes more studies addressing topics
      of surgical management and outcomes. The ability to appraise the literature in
      this fashion is worthwhile to those seeking a better understanding of the science
      underlying modern clinical practice and is thus a highly valuable tool for
      neurosurgical residents, program directors, and neuroscientists as they acquire
      an understanding of modern neurosurgery and its scientific foundation.

PMID- 28438653
TI  - The Fate of Side Branches Covered by Flow Diverters-Results from 140 Patients.
AB  - BACKGROUND: Flow diverter stents (FDS) are a recognized treatment option for
      intracranial aneurysms. There remain ongoing concerns regarding the safety of
      FDS, especially regarding the fate of covered side branches. We report the
      patency of side branches covered by FDS. METHODS: We retrospectively reviewed our
      database of prospectively collected information for all patients treated with FDS
      for an unruptured saccular aneurysm of the clinoid, ophthalmic, and terminating
      segments of the internal carotid artery between September 2009 and July 2016. The
      aneurysm location, fundus size, and the state of covered branches at last
      angiography were recorded compared with preoperative angiography. RESULTS: We
      identified 140 patients, with 147 aneurysms, who met our inclusion criteria. Five
      patients had bilateral aneurysms. There were 31 male patients in our cohort
      (21.9%) and the mean average age was 56.2 +/- 13.7 years. Sixty-seven aneurysms
      arose from the communicating, 58 from the ophthalmic, and 22 from the clinoidal
      segments. At last follow-up (mean, 22.3 months) 116 aneurysms were completely
      occluded (78.3%). On the most recent angiogram, 7 ophthalmic (5.3%), 20 posterior
      communicating (42.6%), 0 anterior choroidal (0%), and 2 anterior cerebral
      arteries (14.3%) were completely occluded. Reduced vessel caliber was seen in 11
      ophthalmic (8.3%), 3 posterior communicating (6.4%), 0 anterior choroidal, and 6
      anterior cerebral arteries (42.9%). One patient died during follow-up.
      CONCLUSIONS: The side branch occlusion rate was 20% and included ophthalmic,
      posterior communicating, and anterior cerebral arteries. Consistent with other
      studies, we did not see occlusion of the anterior choroidal artery.

PMID- 28438654
TI  - Dysembryoplastic Neuroectodermal Tumor: An Analysis from the Surveillance,
      Epidemiology, and End Results Program, 2004-2013.
AB  - BACKGROUND: Dysembryoplastic neuroectodermal tumor (DNT) is a rare neoplasm.
      Though the pathology is commonly considered benign, there have been various
      reports documenting rapid growth, recurrence/progression, sudden death, and
      malignant transformation. Most studies have addressed outcomes regarding seizure
      control, but limited data exist regarding incidence and survival. Consequently,
      we explore the Surveillance, Epidemiology, and End Results (SEER) database to
      explore the epidemiology of DNT. METHODS: From the SEER-18 registry database,
      information from all patients diagnosed with intracranial DNT between 2004 and
      2013 was extracted, including age, sex, race, marital status, tumor location,
      tumor size, receipt of surgery, extent of primary surgery, receipt of radiation,
      and follow-up data. Age-adjusted incidence rates and overall survival (OS) were
      calculated. A Cox proportional hazards model was used to assess relationships
      between various demographic/treatment variables and OS. RESULTS: A total of 381
      cases were identified in the SEER-18 database. The incidence of DNT within the
      large subset of the United States population represented by SEER was 0.033 per
      100,000 person-years (95% confidence interval [CI], 0.030-0.037). The median
      duration of follow-up was 50 months. The median OS was not attained. The 3-, 5-,
      and 9-year OS was 99.363% (95% CI, 97.428%-99.844%), 97.993% (95% CI, 95.168%
      99.174%), and 96.296% (95% CI, 91.834%-98.341%), respectively. Seven of the 381
      patients passed at their last follow up. Of all demographic/treatment factors,
      only receipt of radiation demonstrated a significant relationship with OS (hazard
      ratio, 0.051; 95% CI, 0.01-0.267; P < 0.01). CONCLUSIONS: Although the prognosis
      for DNT is generally favorable, the pathology can lead to poor outcomes in rare
      cases. Common demographic factors, treatment with surgery, and the extent of
      surgical resection did not show significant associations with OS. In contrast,
      treatment with radiation was associated with poorer OS.

PMID- 28438655
TI  - Assessing the Relevancy of "Citation Classics" in Neurosurgery. Part II:
      Foundational Papers in Neurosurgery.
AB  - BACKGROUND: The second part of this study reanalyzes Ponce and Lozano's (2010)
      list of classics to create a new list of "foundational" articles in neurosurgery.
      Ponce and Lozano (2010) previously published a list of 106 neurosurgery classics,
      as defined by Garfield and his 400 citation criterion. METHODS: We used the Web
      of Science citation reports to create graphs for each study showing the total
      citations it received as a function of time. Each graph was subjectively analyzed
      independently and scored as "foundational" or "classic only," based on whether
      the trend of citations received per year was uptrending, neutral, or
      downtrending. RESULTS: Of the 101 evaluated classics, 53 qualified as
      foundational. Over half of these studies were published in Journal of
      Neurosurgery (13), New England Journal of Medicine (12), or Lancet (5). Grading
      systems, randomized trials, and prospective studies were most likely to achieve
      foundational status. Only 30% of functional and 17% of endovascular classics
      qualified as foundational (compared with 100% of spine classics), suggesting that
      these fields are rapidly changing or less mature subspecialties still developing
      a foundational literature base. CONCLUSION: By assessing citation counts as a
      function of time, we are able to differentiate classic neurosurgical studies that
      are critical to modern-day practice from those that are primarily of historic
      interest. Given the exponential growth of literature in our field, analyses such
      as these will become increasingly important to both trainees and senior
      neurosurgeons who strive to educate themselves on the data that drive modern-day
      clinical decision making.

PMID- 28438656
TI  - Is There a Formula for Residency Selection of Future Academic Neurosurgeons?

PMID- 28438657
TI  - The thiol of human serum albumin: Acidity, microenvironment and mechanistic
      insights on its oxidation to sulfenic acid.
AB  - Human serum albumin (HSA) has a single reduced cysteine residue, Cys34, whose
      acidity has been controversial. Three experimental approaches (pH-dependence of
      reactivity towards hydrogen peroxide, ultraviolet titration and infrared
      spectroscopy) are used to determine that the pKa value in delipidated HSA is
      8.1+/-0.2 at 37 degrees C and 0.1M ionic strength. Molecular dynamics simulations
      of HSA in the sub-microsecond timescale show that while sulfur exposure to
      solvent is limited and fluctuating in the thiol form, it increases in the
      thiolate, stabilized by a persistent hydrogen-bond (HB) network involving Tyr84
      and bridging waters to Asp38 and Gln33 backbone. Insight into the mechanism of
      Cys34 oxidation by H2O2 is provided by ONIOM(QM:MM) modeling including quantum
      water molecules. The reaction proceeds through a slightly asynchronous SN2
      transition state (TS) with calculated Delta?G and Delta?H barriers at 298K of
      respectively 59 and 54kJmol-1 (the latter within chemical accuracy from the
      experimental value). A post-TS proton transfer leads to HSA-SO- and water as
      products. The structured reaction site cages H2O2, which donates a strong HB to
      the thiolate. Loss of this HB before reaching the TS modulates Cys34
      nucleophilicity and contributes to destabilize H2O2. The lack of reaction-site
      features required for differential stabilization of the TS (positive charges,
      H2O2 HB strengthening) explains the striking difference in kinetic efficiency for
      the same reaction in other proteins (e.g. peroxiredoxins). The structured HB
      network surrounding HSA-SH with sequestered waters carries an entropic penalty on
      the barrier height. These studies contribute to deepen the understanding of the
      reactivity of HSA-SH, the most abundant thiol in human plasma, and in a wider
      perspective, provide clues on the key aspects that modulate thiol reactivity
      against H2O2.

PMID- 28438658
TI  - Antioxidants reduce neurodegeneration and accumulation of pathologic Tau proteins
      in the auditory system after blast exposure.
AB  - Cochlear neurodegeneration commonly accompanies hair cell loss resulting from
      aging, ototoxicity, or exposures to intense noise or blast overpressures.
      However, the precise pathophysiological mechanisms that drive this degenerative
      response have not been fully elucidated. Our laboratory previously demonstrated
      that non-transgenic rats exposed to blast overpressures exhibited marked somatic
      accumulation of neurotoxic variants of the microtubule-associated protein, Tau,
      in the hippocampus. In the present study, we extended these analyses to examine
      neurodegeneration and pathologic Tau accumulation in the auditory system in
      response to blast exposure and evaluated the potential therapeutic efficacy of
      antioxidants on short-circuiting this pathological process. Blast injury induced
      ribbon synapse loss and retrograde neurodegeneration in the cochlea in untreated
      animals. An accompanying perikaryal accumulation of neurofilament light chain and
      pathologic Tau oligomers were observed in neurons from both the peripheral and
      central auditory system, spanning from the spiral ganglion to the auditory
      cortex. Due to its coincident accumulation pattern and well-documented
      neurotoxicity, our results suggest that the accumulation of pathologic Tau
      oligomers may actively contribute to blast-induced cochlear neurodegeneration.
      Therapeutic intervention with a combinatorial regimen of 2,4-disulfonyl alpha
      phenyl tertiary butyl nitrone (HPN-07) and N-acetylcysteine (NAC) significantly
      reduced both pathologic Tau accumulation and indications of ongoing
      neurodegeneration in the cochlea and the auditory cortex. These results
      demonstrate that a combination of HPN-07 and NAC administrated shortly after a
      blast exposure can serve as a potential therapeutic strategy for preserving
      auditory function among military personnel or civilians with blast-induced
      traumatic brain injuries.

PMID- 28438660
TI  - Reaction of hypotaurine or taurine with superoxide produces the organic
      peroxysulfonic acid peroxytaurine.
AB  - Hypotaurine and taurine are amino acid derivatives and abundant molecules in many
      eukaryotes. The biological reaction in which hypotaurine is converted to taurine
      remains poorly understood. Here, hypotaurine and taurine were observed to react
      with superoxide anion in vitro to form the novel molecule peroxytaurine. In
      contrast, hypotaurine reacts with hydrogen peroxide to form taurine, but taurine
      does not react with hydrogen peroxide in vitro. Mass and NMR spectrometry as well
      as FTIR and Raman spectroscopy support the molecular characterization of
      peroxytaurine. Gravitometric and spectroscopy experiments suggest a stoichiometry
      of two superoxide anions reacting with one hypotaurine or two taurines. The newly
      identified molecule is a semi-stable, organic peroxysulfonic acid that may be an
      intermediate metabolite in taurine synthesis.

PMID- 28438659
TI  - The NRF2 activator DH404 attenuates adverse ventricular remodeling post
      myocardial infarction by modifying redox signalling.
AB  - BACKGROUND: The novel synthetic triterpenoid, bardoxolone methyl, has the ability
      to upregulate cytoprotective proteins via induction of the nuclear factor
      erythroid-2-related factor 2 (Nrf2) pathway. This makes it a promising
      therapeutic agent in disease states characterized by dysregulated oxidative
      signalling. We have examined the effect of a Nrf2 activator, dihydro-CDDO
      trifluoroethyl amide (DH404), a derivative of bardoxolone methyl, on post-infarct
      cardiac remodeling in rats. METHODS/RESULTS: DH404, administered from day 2 post
      myocardial infarction (MI: 30min transient ischemia followed by reperfusion)
      resulted in almost complete protection against adverse ventricular remodeling as
      assessed at day 28 (left ventricular end-systolic area: sham 0.14+/-0.01cm2, MI
      vehicle 0.29+/-0.04cm2 vs. MI DH404 0.18+/-0.02cm2, P<0.05); infarct size (21.3+/
      3.4% MI vehicle vs. 10.9+/-2.3% MI DH404, P<0.05) with associated benefits on
      systolic function (fractional shortening: sham 71.9+/-2.6%, MI vehicle 36.2+/
      1.9% vs. MI DH404 58.6+/-4.0%, P<0.05). These structural and functional benefits
      were associated with lower myocardial expression of atrial natriuretic peptide
      (ANP, P<0.01 vs. MI vehicle), and decreased fibronectin (P<0.01 vs. MI vehicle)
      in DH404-treated MI rats at 28 days. MI increased glutathionylation of
      endothelial nitric oxide synthase (eNOS) in vitro - a molecular switch that
      uncouples the enzyme, increasing superoxide production and decreasing nitric
      oxide (NO) bioavailability. MI-induced eNOS glutathionylation was substantially
      ameliorated by DH404. An associated increase in glutaredoxin 1 (Grx1) co
      immunoprecipitation with eNOS without a change in expression was mechanistically
      intriguing. Indeed, in parallel in vitro experiments, silencing of Grx1 abolished
      the protective effect of DH404 against Angiotensin II-induced eNOS uncoupling.
      CONCLUSION: The bardoxolone derivative DH404 significantly attenuated cardiac
      remodeling post MI, at least in part, by re-coupling of eNOS and increasing the
      functional interaction of Grx1 with eNOS. This agent may have clinical benefits
      protecting against post MI cardiomyopathy.

PMID- 28438661
TI  - Systematic review of the potential adverse effects of caffeine consumption in
      healthy adults, pregnant women, adolescents, and children.
AB  - To date, one of the most heavily cited assessments of caffeine safety in the peer
      reviewed literature is that issued by Health Canada (Nawrot et al., 2003). Since
      then, >10,000 papers have been published related to caffeine, including hundreds
      of reviews on specific human health effects; however, to date, none have compared
      the wide range of topics evaluated by Nawrot et al. (2003). Thus, as an update to
      this foundational publication, we conducted a systematic review of data on
      potential adverse effects of caffeine published from 2001 to June 2015. Subject
      matter experts and research team participants developed five PECO (population,
      exposure, comparator, and outcome) questions to address five types of outcomes
      (acute toxicity, cardiovascular toxicity, bone and calcium effects, behavior, and
      development and reproduction) in four healthy populations (adults, pregnant
      women, adolescents, and children) relative to caffeine intake doses determined
      not to be associated with adverse effects by Health Canada (comparators: 400
      mg/day for adults [10 g for lethality], 300 mg/day for pregnant women, and 2.5
      mg/kg/day for children and adolescents). The a priori search strategy identified
      >5000 articles that were screened, with 381 meeting inclusion/exclusion criteria
      for the five outcomes (pharmacokinetics was addressed contextually, adding 46
      more studies). Data were extracted by the research team and rated for risk of
      bias and indirectness (internal and external validity). Selected no- and low
      effect intakes were assessed relative to the population-specific comparator.
      Conclusions were drawn for the body of evidence for each outcome, as well as
      endpoints within an outcome, using a weight of evidence approach. When the total
      body of evidence was evaluated and when study quality, consistency, level of
      adversity, and magnitude of response were considered, the evidence generally
      supports that consumption of up to 400 mg caffeine/day in healthy adults is not
      associated with overt, adverse cardiovascular effects, behavioral effects,
      reproductive and developmental effects, acute effects, or bone status. Evidence
      also supports consumption of up to 300 mg caffeine/day in healthy pregnant women
      as an intake that is generally not associated with adverse reproductive and
      developmental effects. Limited data were identified for child and adolescent
      populations; the available evidence suggests that 2.5 mg caffeine/kg body
      weight/day remains an appropriate recommendation. The results of this systematic
      review support a shift in caffeine research to focus on characterizing effects in
      sensitive populations and establishing better quantitative characterization of
      interindividual variability (e.g., epigenetic trends), subpopulations (e.g.,
      unhealthy populations, individuals with preexisting conditions), conditions
      (e.g., coexposures), and outcomes (e.g., exacerbation of risk-taking behavior)
      that could render individuals to be at greater risk relative to healthy adults
      and healthy pregnant women. This review, being one of the first to apply
      systematic review methodologies to toxicological assessments, also highlights the
      need for refined guidance and frameworks unique to the conduct of systematic
      review in this field.

PMID- 28438663
TI  - Acute effects of amitriptyline on adult zebrafish: Potential relevance to
      antidepressant drug screening and modeling human toxidromes.
AB  - The need to develop novel antidepressants is an emerging problem in biomedicine.
      An aquatic vertebrate species, the zebrafish (Danio rerio) may serve as a useful
      in-vivo screen for CNS drugs, and displays high sensitivity to a wide range of
      antidepressants. Amitriptyline is a commonly used tricyclic antidepressant which
      acts primarily as a serotonin and noradrenaline reuptake inhibitor. Here, we
      characterize drug-induced behavioral and neurochemical responses in adult
      zebrafish following their acute exposure to amitriptyline. Overall, the drug at 1
      and 5mg/L significantly increased time spent in top and shortened the latency to
      enter it, thereby paralleling recent reports on zebrafish 'serotonin toxicity
      like behavior' caused by various serotonergic agents. The 10mg/L dose of the drug
      also significantly decreased top entries and maximal velocity and evoked overt
      ataxia, likely due to emerging non-specific toxic effects. Amitriptyline at 5 and
      10mg/L also dose-dependently increased serotonin turnover, but not noradrenaline
      levels, in zebrafish whole-brain samples. Overall, zebrafish high sensitivity to
      acute effects of amitriptyline can help improve our understanding of
      psychopharmacological profiles of this compound and the related CNS drugs, and
      contributes further to the development of aquatic experimental models of human
      toxidromes.

PMID- 28438662
TI  - Never let it go: Stopping key mechanisms underlying metastasis to fight
      pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm,
      predicted to become the second leading cause of cancer-related deaths before
      2030. This dismal trend is mainly due to lack of effective treatments against its
      metastatic behavior. Therefore, a better understanding of the key mechanisms
      underlying metastasis should provide new opportunities for therapeutic purposes.
      Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and
      progression, such as SMAD4 loss, are also implicated in metastasis. Recently,
      microRNAs have been shown to play a regulatory role in the metastatic behavior of
      many tumors, including PDAC. In particular, miR-10 and miR-21 have appeared as
      master regulators of the metastatic program, while members of the miR-200 family
      are involved in the epithelial-to-mesenchymal switch, favoring cell migration and
      invasiveness. Several studies have also found a close relationship between cancer
      stem cells (CSCs) and biological features of metastasis, and the CSC markers
      ALDH1, ABCG2 and c-Met are expressed at high levels in metastatic PDAC cells.
      Emerging evidence reveals that exosomes are involved in the modulation of the
      tumor microenvironment and can initiate PDAC pre-metastatic niche formation in
      the liver and lungs. In this review, we provide an overview of the role of all
      these pivotal factors in the metastatic behavior of PDAC, and discuss their
      potential exploitation in the clinic to improve current therapeutics and identify
      new drug targets.

PMID- 28438664
TI  - Simultaneous measurement of Aspartate, NAA, and NAAG using HERMES spectral
      editing at 3 Tesla.
AB  - It has previously been shown that the HERMES method ('Hadamard Encoding and
      Reconstruction of MEGA-Edited Spectroscopy') can be used to simultaneously edit
      pairs of metabolites (such as N-acetyl-aspartate (NAA) and N-acetyl aspartyl
      glutamate (NAAG), or glutathione and GABA). In this study, HERMES is extended for
      the simultaneous editing of three overlapping signals, and illustrated for the
      example of NAA, NAAG and Aspartate (Asp). Density-matrix simulations were
      performed in order to optimize the HERMES sequence. The method was tested in NAA
      and Asp phantoms, and applied to the centrum semiovale of the nine healthy
      control subjects that were scanned at 3T. Both simulations and phantom
      experiments showed similar metabolite multiplet patterns with good segregation of
      all three metabolites. In vivo measurements show consistent relative signal
      intensities and multiplet patterns with concentrations in agreement with
      literature values. Simulations indicate co-editing of glutathione, glutamine, and
      glutamate, but their signals do not significantly overlap with the detected
      aspartyl resonances. This study demonstrates that a four-step Hadamard-encoded
      editing scheme can be used to simultaneously edit three otherwise overlapping
      metabolites, and can measure NAA, NAAG, and Asp in vivo in the brain at 3T with
      minimal crosstalk.

PMID- 28438665
TI  - Effective connectivity gateways to the Theory of Mind network in processing
      communicative intention.
AB  - An Intention Processing Network (IPN), involving the medial prefrontal cortex,
      precuneus, bilateral posterior superior temporal sulcus, and temporoparietal
      junctions, plays a fundamental role in comprehending intentions underlying action
      goals. In a previous fMRI study, we showed that, depending on the linguistic or
      extralinguistic (gestural) modality used to convey the intention, the IPN is
      complemented by activation of additional brain areas, reflecting distinct
      modality-specific input gateways to the IPN. These areas involve, for the
      linguistic modality, the left inferior frontal gyrus (LIFG), and for the
      extralinguistic modality, the right inferior frontal gyrus (RIFG). Here, we
      tested the modality-specific gateway hypothesis, by using DCM to measure inter
      regional functional integration dynamics between the IPN and LIFG/RIFG gateways.
      We found strong evidence of a well-defined effective connectivity architecture
      mediating the functional integration between the IPN and the inferior frontal
      cortices. The connectivity dynamics indicate a modality-specific propagation of
      stimulus information from LIFG to IPN for the linguistic modality, and from RIFG
      to IPN for the extralinguistic modality. Thus, we suggest a functional model in
      which the modality-specific gateways mediate the structural and semantic decoding
      of the stimuli, and allow for the modality-specific communicative information to
      be integrated in Theory of Mind inferences elaborated through the IPN.

PMID- 28438666
TI  - How to choose the right MR sequence for your research question at 7T and above?
AB  - The choice of a pulse sequence at ultra-high field can be influenced by a number
      of considerations and constraints that are not always the same as those at lower
      fields. Foremost amongst these is of course the information required and the time
      available, but considerations of static main field- and transmit field-
      inhomogeneities as well as power deposition can also play an important role. In
      this review we first briefly examine the characteristics of high field MRI, and
      then describe the performance and constraints relevant to the major imaging
      readouts, and their implementation with parallel imaging techniques. In the main
      body of the text we review the main current applications of neuro imaging at 7T:
      functional brain imaging; diffusion weighted imaging; structural imaging; and
      conclude with a brief summary of time of flight angiography. FMRI is explored in
      the context both of whole brain coverage, and for high resolution imaging of
      cortical layers and columns. The major pulse sequences considered include 3D and
      2D EPI multi-echo EPI and spin echo EPI. Diffusion weighted single shot EPI is
      the sequence of choice with segmented approaches having some niche applications.
      In structural imaging a distinction is made between qualitative and quantitative
      approaches, with both T1 and T2*-based approaches considered. The application of
      these techniques to important brain pathologies is shown, in addition to their
      capability for high resolution imaging of cortical and sub-cortical anatomy. The
      advantages of 7T for time of flight angiography at 7T are elucidated and
      exemplary applications given.

PMID- 28438667
TI  - Watching the brain recalibrate: Neural correlates of renormalization during face
      adaptation.
AB  - The face perception system flexibly adjusts its neural responses to current face
      exposure, inducing aftereffects in the perception of subsequent faces. For
      instance, adaptation to expanded faces makes undistorted faces appear compressed,
      and adaptation to compressed faces makes undistorted faces appear expanded. Such
      distortion aftereffects have been proposed to result from renormalization, in
      which the visual system constantly updates a prototype according to the adaptors'
      characteristics and evaluates subsequent faces relative to that. However,
      although consequences of adaptation are easily observed in behavioral
      aftereffects, it has proven difficult to observe renormalization during
      adaptation itself. Here we directly measured brain responses during adaptation to
      establish a neural correlate of renormalization. Given that the face-evoked
      occipito-temporal P2 event-related brain potential has been found to increase
      with face prototypicality, we reasoned that the adaptor-elicited P2 could serve
      as an electrophysiological indicator for renormalization. Participants adapted to
      sequences of four distorted (compressed or expanded) or undistorted faces,
      followed by a slightly distorted test face, which they had to classify as
      undistorted or distorted. We analysed ERPs evoked by each of the adaptors and
      found that P2 (but not N170) amplitudes evoked by consecutive adaptor faces
      exhibited an electrophysiological pattern of renormalization during adaptation to
      distorted faces: P2 amplitudes evoked by both compressed and expanded adaptors
      significantly increased towards asymptotic levels as adaptation proceeded. P2
      amplitudes were smallest for the first adaptor, significantly larger for the
      second, and yet larger for the third adaptor. We conclude that the sensitivity of
      the occipito-temporal P2 to the perceived deviation of a face from the norm makes
      this component an excellent tool to study adaptation-induced renormalization.

PMID- 28438668
TI  - Non-neuronal neuropeptide Y and its receptors during acute rejection of rat
      pulmonary allografts.
AB  - This study tested the hypothesis that neuropeptide Y (NPY) and NPY receptors 1
      (Y1) and 2 (Y2) participate in lung allograft rejection. Inflammation in grafts
      may include interaction between blood leukocytes and graft endothelial cells and
      marked accumulation of intravascular blood leukocytes. Fewer leukocytes
      accumulate in lung than in kidney allografts. Lung transplantion was performed in
      the Dark Agouti to Lewis rat strain combination. Intravascular and intraalveolar
      leukocytes were isolated from the grafts, and we evaluated the mRNA expression of
      NPY, Y1, and Y2 by real-time RT-PCR as well as the peptide expression of NPY by
      radioimmunoassay and immunohistochemistry. NPY and Y1 were expressed by pulmonary
      intravascular and intraalveolar leukocytes. Y1 was up-regulated by pulmonary
      intravascular and intraalveolar leukocytes during allograft rejection while Y2
      could not be detected. Higher NPY expression levels in intravascular leukocytes
      were observed in lung compared to kidney allografts, which were investigated
      previously. Our findings suggest that an increased leukocytic expression of NPY
      in lung compared to kidney allografts results in a reduced accumulation of
      leukocytes in allograft vessels.

PMID- 28438669
TI  - The effects of Chinese medicines on cAMP/PKA signaling in central nervous system
      dysfunction.
AB  - Neuropathological injury in the mammalian adult central nervous system (CNS) may
      cause axon disruption, neuronal death and lasting neurological deficits. Failure
      of axon regeneration is one of the major challenges for CNS functional recovery.
      Recently, the cAMP/PKA signaling pathway has been proven to be a critical
      regulator for neuronal regeneration, neuroplasticity, learning and memory. Also,
      previous studies have shown the effects of Chinese medicines on the prevention
      and treatment of CNS dysfunction mediated in part by cAMP/PKA signaling. In this
      review, the authors discuss current knowledge of the role of cAMP/PKA signaling
      pathway in neuronal regeneration and provide an overview of the Chinese medicines
      that may enable CNS functional recovery via this signaling pathway.

PMID- 28438670
TI  - Epidemiological features and genetic characterization of virus strains in
      rotavirus associated gastroenteritis in children of Odisha in Eastern India.
AB  - We have studied the clinical characteristics, severity and seasonality of
      rotavirus infection and prevalent genotypes in 652 non-rota vaccinated children
      in Odisha in eastern India. P genotypes were analysed for their association with
      host blood group antigens. P type of the virus is determined by the VP8* gene,
      and specific recognition of A - type of Histo - blood group antigen by P[14]VP8*
      has been reported. VP4, VP7 and VP6 genes of commonly identified G1P[8] strain
      were compared with genes of the same strain isolated from other parts of India,
      elsewhere and strains used for Rotarix and Rotateq vaccines. In 54.75% of
      children with gastroenteritis, rota virus was found. 9.65% of children had
      moderate, 78.07% severe, and 12.28% very severe disease as assessed using the
      Vesikari scoring system. The incidence of infection was highest during winter
      months. There was no association between any blood group and specific P
      genotypes. G1P[8] was the commonest cause of gastroenteritis, followed by
      G1P[11], G3P[8], G9P[8], G2P[4], G2P[6], G9P[4], G9P[11] and G1P[6]. Predominant
      G genotypes identified were G1 (72.9%), G9 (10.81%), G2 (8.10%) and G3 (8.10%).
      Sequence analysis of the VP7 gene, placed the G1P[8] strain in lineage 1 and of
      VP6 gene placed nine G1P[8] strains in subgroup II and one in subgroup I. The VP7
      gene segment of two Odisha G1P[8] strains were found to cluster relatively close
      to the VP7 sequences of Rotarix vaccine. Antigenic differences were found with
      vaccine strains. Ten G1P[8] strains sequenced for the VP4 gene had 91-93%
      nucleotide and 92-96% amino acid identity with Rotateq vaccine P[8]). Rotarix
      vaccine VP4 had 89-91% nucleotide and 90-92% amino acid identity. Our findings
      indicate genetic variability of rotavirus strains circulating in the region and
      are significant, given the introduction of rota vaccination in the State.

PMID- 28438671
TI  - Alkaline pH induces IRR-mediated phosphorylation of IRS-1 and actin cytoskeleton
      remodeling in a pancreatic beta cell line.
AB  - Secretion of mildly alkaline (pH 8.0-8.5) juice to intestines is one of the key
      functions of the pancreas. Recent reports indicate that the pancreatic duct
      system containing the alkaline juice may adjoin the endocrine cells of pancreatic
      islets. We have previously identified the insulin receptor-related receptor (IRR)
      that is expressed in islets as a sensor of mildly alkaline extracellular media.
      In this study, we show that those islet cells that are in contact with the
      excretory ducts are also IRR-expressing cells. We further analyzed the effects of
      alkaline media on pancreatic beta cell line MIN6. Activation of endogenous IRR
      but not of the insulin receptor was detected that could be inhibited with
      linsitinib. The IRR autophosphorylation correlated with pH-dependent linsitinib
      sensitive activation of insulin receptor substrate 1 (IRS-1), the primary adaptor
      in the insulin signaling pathway. However, in contrast with insulin stimulation,
      no protein kinase B (Akt/PKB) phosphorylation was detected as a result of alkali
      treatment. We observed overexpression of several early response genes (EGR2,
      IER2, FOSB, EGR1 and NPAS4) upon alkali treatment of MIN6 cells but those were
      IRR-independent. The alkaline medium but not insulin also triggered actin
      cytoskeleton remodeling that was blocked by pre-incubation with linsitinib. We
      propose that the activation of IRR by alkali might be part of a local loop of
      signaling between the exocrine and endocrine parts of the pancreas where
      alkalinization of the juice facilitate insulin release that increases the volume
      of secreted juice to control its pH and bicabonate content.

PMID- 28438672
TI  - The Management Strategy of Benign Solitary Intraductal Papilloma on Breast Core
      Biopsy.
AB  - BACKGROUND: Intraductal papilloma (IDP) is well-known as one of the common benign
      breast lesions requiring excision. However, treatment of IDP without atypia is
      controversial. The aim of our study was to determine the proper management of
      solitary IDP by core needle biopsy (CNB). PATIENTS AND METHODS: We
      retrospectively reviewed patients with solitary IDP confirmed by CNB from March
      2003 to March 2015. We collected data about final pathology after excision, as
      well as clinical, histologic, and radiologic findings at initial diagnosis. The
      final pathology was categorized as benign or malignant. We evaluated the rate of
      upgrade to malignancy and factors associated with malignancy. RESULTS: We
      identified 405 patients who presented benign solitary IDP by CNB. The mean age
      was 46.1 years (range, 15-86 years). In total, 135 patients underwent surgical
      excision, and 211 underwent vacuum-assisted excision. Of 346 patients, malignant
      lesions were found in 8 patients (2.3%): 7 underwent surgical excision, and 1
      underwent vacuum-assisted excision. Only the size of IDP was significantly
      associated with cancer upgrade (P = .003). CONCLUSIONS: Our study shows that
      overall malignancy upgrade rate of benign solitary IDP after excision is very low
      (2.3%). Even when the size of IDP was less than 1 cm, the upgrade rate to cancer
      was only 0.9%. Therefore, for patients with small solitary IDP, we recommend
      close follow-up with ultrasound instead of excision.

PMID- 28438673
TI  - Infants and adults have similar regional functional brain organization for the
      perception of emotions.
AB  - An infant's ability to perceive emotional facial expressions is critical for
      developing social skills. Infants are tuned to faces from early in life, however
      the functional organization of the brain that supports the processing of
      emotional faces in infants is still not well understood. We recorded
      electroencephalography (EEG) brain responses in 8-10 month old infants and adults
      and applied graph theory analysis on the functional connections to compare the
      network organization at the global and the regional levels underlying the
      perception of negative and positive dynamic facial expressions (happiness and
      sadness). We first show that processing of dynamic emotional faces occurs across
      multiple brain regions in both infants and adults. Across all brain regions, at
      the global level, network density was higher in the infant group in comparison
      with adults suggesting that the overall brain organization in relation to emotion
      perception is still immature in infancy. In contrast, at the regional levels, the
      functional characteristics of the frontal and parietal nodes were similar between
      infants and adults, suggesting that functional regional specialization for
      emotion perception is already established at this age. In addition, in both
      groups the occipital, parietal and temporal nodes appear to have the strongest
      influence on information flow within the network. These results suggest that
      while the global organization for the emotion perception of sad and happy
      emotions is still under development, the basic functional network organization at
      the regional level is already in place early in infancy.

PMID- 28438675
TI  - Integrating cell biology and proteomic approaches in plants.
AB  - : Significant improvements of protein extraction, separation, mass spectrometry
      and bioinformatics nurtured advancements of proteomics during the past years. The
      usefulness of proteomics in the investigation of biological problems can be
      enhanced by integration with other experimental methods from cell biology,
      genetics, biochemistry, pharmacology, molecular biology and other omics
      approaches including transcriptomics and metabolomics. This review aims to
      summarize current trends integrating cell biology and proteomics in plant
      science. Cell biology approaches are most frequently used in proteomic studies
      investigating subcellular and developmental proteomes, however, they were also
      employed in proteomic studies exploring abiotic and biotic stress responses,
      vesicular transport, cytoskeleton and protein posttranslational modifications.
      They are used either for detailed cellular or ultrastructural characterization of
      the object subjected to proteomic study, validation of proteomic results or to
      expand proteomic data. In this respect, a broad spectrum of methods is employed
      to support proteomic studies including ultrastructural electron microscopy
      studies, histochemical staining, immunochemical localization, in vivo imaging of
      fluorescently tagged proteins and visualization of protein-protein interactions.
      Thus, cell biological observations on fixed or living cell compartments, cells,
      tissues and organs are feasible, and in some cases fundamental for the validation
      and complementation of proteomic data. SIGNIFICANCE: Validation of proteomic data
      by independent experimental methods requires development of new complementary
      approaches. Benefits of cell biology methods and techniques are not sufficiently
      highlighted in current proteomic studies. This encouraged us to review most
      popular cell biology methods used in proteomic studies and to evaluate their
      relevance and potential for proteomic data validation and enrichment of purely
      proteomic analyses. We also provide examples of representative studies combining
      proteomic and cell biology methods for various purposes. Integrating cell biology
      approaches with proteomic ones allow validation and better interpretation of
      proteomic data. Moreover, cell biology methods remarkably extend the knowledge
      provided by proteomic studies and might be fundamental for the functional
      complementation of proteomic data. This review article summarizes current
      literature linking proteomics with cell biology.

PMID- 28438676
TI  - Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood
      Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.
AB  - For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an
      important cause of treatment failure after unrelated cord blood transplant
      (UCBT). Compared with other donor sources, relapse is similar or even reduced
      after UCBT despite less graft-versus-host disease (GVHD). We performed a
      retrospective analysis to identify risk factors associated with the 5-year
      cumulative incidence of relapse after UCBT. In this retrospective, registry-based
      study, we examined the outcomes of 640 children (<18 years) with ALL in first
      complete remission (CR1; n = 257, 40%) or second complete remission (CR2; n =
      383, 60%) who received myeloablative conditioning followed by a single-unit UCBT
      from 2000 to 2012. Most received antithymocyte globulin (88%) or total body
      irradiation (TBI; 69%), and cord blood grafts were primarily mismatched at 1
      (50%) or 2+ (34%) HLA loci. Considering patients in CR1, the rates of 5-year
      overall survival (OS), leukemia-free survival (LFS), and relapse were 59%, 52%,
      and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to
      IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS,
      LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%,
      respectively. In MVA, longer duration from diagnosis to UCBT (>=30 months) and
      TBI were associated with decreased relapse risk. Importantly, receiving a fully
      HLA matched graft was a strong risk factor for increased relapse in MVA. An
      exploratory analysis of all 640 patients supported the important association
      between the presence of acute GVHD and less relapse but also demonstrated an
      increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a
      graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies
      that promote graft-versus-leukemia while harnessing GVHD should be further
      investigated.

PMID- 28438677
TI  - A prospective, comparative study of severe neurological and uncomplicated hand,
      foot and mouth forms of paediatric enterovirus 71 infections.
AB  - OBJECTIVES: In this study, we document the clinical characteristics and
      investigated risk factors for uncomplicated and severe forms of EV-A71 disease in
      Cambodian children. METHODS: From March to July 2014 inclusive, all patients with
      suspicion of EV-A71 infection presenting to Kantha Bopha Hospitals in Phnom Penh
      and Siem Reap and confirmed by the Virology Unit at the Institut Pasteur du
      Cambodge were prospectively enrolled in this study. Throat swabs, rectal swabs
      and serum samples were collected from all consecutive patients with suspected EV
      A71 infection. In addition, CSF was also collected from patients with suspected
      EV-A71 associated encephalitis. A total of 122 patients (29 with uncomplicated
      disease and 93 with severe disease) with confirmed EV-A71 infection with all
      available demographic and clinical data for clinical classification and further
      analysis were included in the study. RESULTS: In this prospective EV-A71 study in
      Cambodia, we confirmed the previously reported association of male gender and
      absence of mouth or skin lesions with severe disease. We also highlighted the
      strong association of neutrophils in blood, but also in CSF in patients with
      pulmonary oedema. More importantly, we identified new putative nutrition-related
      risk factors for severe disease. CONCLUSIONS: EV-A71 is an important cause of
      encephalitis in the Asia-Pacific region. Further studies to determine the risk
      factors associated with severe EV-A71 disease are needed.

PMID- 28438678
TI  - Do photoreceptor cells cause the development of retinal vascular disease?
AB  - The retinal vasculature is affected in a number of clinically important
      retinopathies, including diabetic retinopathy. There has been a considerable
      amount of research into the pathogenesis of retinal microvascular diseases, but
      the potential contribution of the most abundant cell population in the retina,
      photoreceptor cells, has been largely overlooked. This review summarizes ongoing
      research suggesting that photoreceptor cells play a critical role in the
      development of retinal vascular disease in diabetic retinopathy and other
      retinopathies.

PMID- 28438674
TI  - Current state and challenges in developing oral vaccines.
AB  - While vaccination remains the most cost effective strategy for disease
      prevention, communicable diseases persist as the second leading cause of death
      worldwide. There is a need to design safe, novel vaccine delivery methods to
      protect against unaddressed and emerging diseases. Development of vaccines
      administered orally is preferable to traditional injection-based formulations for
      numerous reasons including improved safety and compliance, and easier
      manufacturing and administration. Additionally, the oral route enables
      stimulation of humoral and cellular immune responses at both systemic and mucosal
      sites to establish broader and long-lasting protection. However, oral delivery is
      challenging, requiring formulations to overcome the harsh gastrointestinal (GI)
      environment and avoid tolerance induction to achieve effective protection. Here
      we address the rationale for oral vaccines, including key biological and
      physicochemical considerations for next-generation oral vaccine design.

PMID- 28438679
TI  - A proposal for early and personalized treatment of diabetic retinopathy based on
      clinical pathophysiology and molecular phenotyping.
AB  - This paper presents a new approach to the prevention and treatment of early stage
      diabetic retinopathy before vision is severely impaired. This approach includes
      two major steps. The first step is to understand the mechanisms of vision
      impairment and classify diabetic retinopathy on the basis of pathophysiologic
      adaptations, rather than on the presence of advanced pathologic lesions, as
      defined by current clinical practice conventions. The second step is to develop
      patient-specific molecular diagnoses of diabetic retinopathy so that patients can
      be treated based on their individual characteristics, a process analogous to the
      individualized diagnosis and treatment of cancer patients. This step is
      illustrated by proteomic analysis of vitreous fluid that reveals evidence of
      neuroretinal degeneration and inflammation, as well as vascular proliferation.
      Together, these steps may lead to improved means to preserve vision in the ever
      increasing number of patients with diabetes worldwide.

PMID- 28438680
TI  - Time course influences transfer of visual perceptual learning across spatial
      location.
AB  - Visual perceptual learning describes the improvement of visual perception with
      repeated practice. Previous research has established that the learning effects of
      perceptual training may be transferable to untrained stimulus attributes such as
      spatial location under certain circumstances. However, the mechanisms involved in
      transfer have not yet been fully elucidated. Here, we investigated the effect of
      altering training time course on the transferability of learning effects.
      Participants were trained on a motion direction discrimination task or a
      sinusoidal grating orientation discrimination task in a single visual hemifield.
      The 4000 training trials were either condensed into one day, or spread evenly
      across five training days. When participants were trained over a five-day period,
      there was transfer of learning to both the untrained visual hemifield and the
      untrained task. In contrast, when the same amount of training was condensed into
      a single day, participants did not show any transfer of learning. Thus, learning
      time course may influence the transferability of perceptual learning effects.

PMID- 28438681
TI  - Immobilized lignin peroxidase from Ganoderma lucidum IBL-05 with improved dye
      decolorization and cytotoxicity reduction properties.
AB  - Use of free microbial enzymes for bioremediation and other industrial
      applications has several disadvantages like low stability and non-reusability in
      repeated batch operations. Immobilized enzymes are stable, recoverable and
      reusable in industrial processes. In this scenario G. lucidum IBL-05 LiP was
      entrapped in Ca-alginate beads using optimum concentrations of Na-alginate (4%),
      calcium chloride (0.2M) and glutraldehyde (0.02%). Optimum pH (pH 5) and
      temperature (55 degrees C) for entrapped LiP were improved as compared to free
      LiP. Catalytic behavior of LiP also significantly enhanced, as Km value (0.25mM)
      decreased and Vmax value (868.6MUmol/min) increased after ca-alginate entrapment
      of LiP. Decolorization efficiencies of Sandal reactive dyes after treating with
      immobilized LiP were in the range of 80-93%. A significant reduction was observed
      in water quality parameters including, BOD (66.44-98.22%), COD (81.34-98.82%) and
      TOC (80.21-97.77%) values. The cytotoxicity values for heamolytic and brine
      shrimp lethality of dye solutions treated with Ca-alginate immobilized LiP
      reduced up to 2.10-5.06% and 5.43-9.23%, respectively. On the basis of reduced
      toxicity and cytotoxicity values, it was concluded that Ca-alginate beads
      entrapped LiP may be an effective biocatalyst for bioremediation of dye based
      textile industry effluents.

PMID- 28438682
TI  - Production, immobilization and thermodynamic studies of free and immobilized
      Aspergillus awamori amylase.
AB  - Enzyme cost, stability and its thermodynamic characteristics are the main
      criteria for industrial use. In this study, Aspergillus awamori amylase was
      constitutively produced using various agro-industrial wastes. Olive oil cake gave
      the highest activity (230U/g). The amylase was partially purified to 2.81-fold
      purification. Immobilization was achieved using different carriers by covalent
      binding. The novel carrier Ca+2 alginate (Alg) starch (St)/polyethyleneimine
      (PEI)/glutaraldehyde (GA), showed the highest operational stability and was
      selected for further studies. The optimum temperature for the free and
      immobilized form was 50 degrees C and 55-60 degrees C, respectively. The
      immobilization process had a major role in improving enzyme thermal stability. In
      comparison to free enzyme, the immobilized form showed the highest optimum
      temperature, activation energy (Ea) and deactivation rate constants (kd). Also,
      t1/2, D-values (decimal reduction time), change in enthalpy (DeltaH degrees 
      kJmol-1), and Gibbs free energy (DeltaG degrees ) increased and was higher than
      the native enzyme within 50-80 degrees C. The magnitude of negative value of
      entropy (DeltaS degrees  kJmol-1) for immobilized enzyme was negative for the
      free and immobilized enzymes revealing that native form of enzyme was in more
      ordered state. Km and Vmax values were slightly affected by the temperature
      variations 40-70 degrees C.

PMID- 28438683
TI  - Identification and expression of piwil2 in turbot Scophthalmus maximus, with
      implications of the involvement in embryonic and gonadal development.
AB  - Piwil2, a member of the Argonaute family, is involved in the biogenesis of PIWI
      interacting RNAs (piRNAs) and plays an important role in regulating
      gametogenesis. In the present study, we identified turbot Scophthalmus maximus
      piwil2 gene, named Smpiwil2, which contained a PAZ domain and a PIWI domain.
      Sequence comparison, genomic structure and phylogenetic analyses showed that
      Smpiwil2 is homologous to that of teleosts and tetrapods. The Smpiwil2 transcript
      showed higher expression in the ovary than in the testis, demonstrating a
      sexually dimorphic gene expression pattern. In situ hybridization (ISH) showed
      that Smpiwil2 was expressed in the oogonia and all the stages of oocytes in the
      ovary as well as in spermatogonia and spermatocytes in the testis. Embryonic
      expression profile revealed that Smpiwil2 was maternally inherited, and its level
      was higher from the zygote to the blastula stage and subsequently decreased until
      hatching. Moreover, a CpG island was predicted to locate in the 5'-flanking
      region of Smpiwil2 gene, and its methylation levels detected by sodium bisulfite
      sequencing showed significant disparity between females and males, implying that
      the sexually dimorphic expression of Smpiwil2 might be regulated by methylation.
      These results indicated that Smpiwil2 had potentially vital functions in
      embryonic and gonadal development in this species. In addition, the temporal and
      sex differences in Smpiwil2 expression indicated that this gene may play
      different roles in gonadal development of different sexes.

PMID- 28438684
TI  - Two spliced isoforms of the sex-determination gene fruitless in the Chinese
      mitten crab Eriocheir sinensis.
AB  - The fruitless (fru) gene plays an important role in the sex determination pathway
      and courtship behavior of Drosophila melanogaster. In the present study, two fru
      isoforms (Esfru1 and Esfru2) were identified from the Chinese mitten crab
      Eriocheir sinensis. Sequence analysis showed that Esfru1 and Esfru2 were encoded
      by the same genomic locus and generated by alternative splicing of pre-mRNA.
      Esfru1 had all introns completely spliced out, while Esfru2 had a longer exon1
      with an additional 78bp sequence. They both contained a conserved BTB domain
      which was also found in D. melanogaster Fru isoforms. Analysis on temporal
      expression profiles of Esfru1-2 (a common region of Esfru1 and Esfru2) and Esfru2
      (a specific region of Esfru2) showed that they expressed in similar patterns
      during embryonic development but in different patterns during larval development.
      The expression of Esfru1-2 decreased gradually from zoea III stage, however,
      Esfru2 increased from zoea IV stage and reached the peak at megalopa stage.
      Expression distribution in tissues and in situ hybridization analysis revealed
      that they showed sexually dimorphic expression in gonads, hepatopancreas and
      brains. Esfru1-2 showed significantly higher expression in female gonads and
      hepatopancreas than in males, but highly expressed in male brains than that in
      females. Interestingly, Esfru2 was displayed in a male-specific manner in each
      tissue, especially in gonads and hepatopancreas. Our results indicate that Esfru1
      might be involved in both sexual brain neuronal structure development and related
      to female-specific character development. Esfru2 may participate in male-specific
      character development. This is the first report that characterizes two spliced
      variants of fru in crustaceans and provides basic information for further
      functional studies of the crab sex-determination mechanism.

PMID- 28438685
TI  - Genotypic detection of the blaCTX-M-1 gene among extended-spectrum beta-lactamase
      producing Enterobacteriaceae.
AB  - OBJECTIVES: Extended-spectrum beta-lactamases (ESBLs), a group of beta-lactamase
      enzymes produced by bacteria in the family Enterobacteriaceae, are becoming a
      major problem in the healthcare community worldwide. Although many attempts have
      been made in the detection of ESBL-producing bacteria, the cost and speed of
      detection remains an important challenge. Therefore, this study aimed to develop
      a rapid, effective and affordable method for detection of the blaCTX-M-1 ESBL
      gene by a loop-mediated isothermal amplification (LAMP) technique. METHODS:
      Clinical ESBL-producing Enterobacteriaceae, including Escherichia coli and
      Klebsiella pneumoniae, were isolated and were used as representative strains. The
      double-disk synergy method was performed to detect ESBL-producing
      Enterobacteriaceae. Performance of the LAMP method in the detection of blaCTX-M-1
      was compared with conventional PCR in terms of sensitivity and specificity.
      RESULTS: The developed LAMP method efficiently identified the presence of the
      blaCTX-M-1 gene in ESBL-producing Enterobacteriaceae. It provided similar results
      to conventional PCR, but the LAMP technique required only 20min of testing time.
      The accuracy of the LAMP method was confirmed by restriction digestion, which
      showed the predicted size of the blaCTX-M-1 gene. In addition, the developed
      method was comparable with PCR that amplified only the target blaCTX-M-1 gene in
      terms of specificity, but LAMP was ca. 1000-fold more sensitive than PCR.
      CONCLUSIONS: A rapid assay to detect ESBL-producing Enterobacteriaceae by a LAMP
      technique was developed in this study. The developed method is sensitive and
      suitable for rapid screening of blaCTX-M-1 in routine laboratories with limited
      resources.

PMID- 28438686
TI  - Expression, purification and molecular characterization of a novel endoglucanase
      protein from Bacillus subtilis SB13.
AB  - Bacillus subtilis strain SB13 which is isolated in our previous work was
      confirmed to produce endoglucanase. In this study, a novel endoglucanase gene
      (accession number: KX576676) was identified and cloned from SB13. Compared with
      other consensus sequence of reported endoglucanase genes in the GenBank database,
      this gene displays five differences (including T740C,A874G,A983G, T1210G and
      T1301C), which leading to five amino acid changes. Homology modeling has
      indicated that these five changes were located in the alpha-helix and random coil
      regions of the glycosyl hydrolase family 5 (GH5) domain, the random coil and beta
      sandwich of the type 3 carbohydrate-binding module (CBM3) domain, and the random
      coil domain. Aprokaryotic expression vector pET30a-endoglucanase was constructed
      and the endoglucanase was induced to express. The expressed endoglucanase was
      confirmed by liquid chromatography-tandem mass spectrometry (LC-MSMS) and
      detected via reaction with carboxymethyl cellulose. In order to obtain the
      highest expression level of endoglucanase, the expression conditions including
      IPTG concentration, temperature and pH were optimized. The recombinant
      endoglucanase protein was purified using a Ni-NTA column, and the 6 * His-tag was
      removed with thrombin. The results showed that both the modified and unmodified
      purified endoglucanase had high activity (7.65 +/- 0.35 U and 15.05 +/- 1.81 U,
      respectively), thus demonstrating the potential use of this enzyme in various
      industrial applications. The substitutions of L247P,N292D, F404V and L434P might
      contribute to the activity of the endoglucanase, and the insertion of a 6 * His
      tag at the N-terminal of the endoglucanase might also affect its activity.

PMID- 28438687
TI  - Dietary nitrite supplementation attenuates cardiac remodeling in l-NAME-induced
      hypertensive rats.
AB  - Loss of nitric oxide (NO) bioavailability underlies the development of
      hypertensive heart disease. We investigated the effects of dietary nitrite on NG
      nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Sprague-Dawley rats
      were divided into five groups: an untreated control group, an l-NAME-treated
      group, and three other l-NAME-treated groups supplemented with 10 mg/L or 100
      mg/L of nitrite or 100 mg/L of captopril in drinking water. After the 8-week
      experimental period, mean arterial blood pressure was measured, followed by
      sampling of blood and heart tissue for assessment of nitrite/nitrate levels in
      the plasma and heart, the plasma level of angiotensin II (AT II), and the heart
      transcriptional levels of AT II type 1 receptor (AT1R), transforming growth
      factor-beta1 (TGF-beta1), and connective tissue proteins such as type 1 collagen
      and fibronectin. Heart tissue was analyzed by histopathological morphometry,
      including assessments of ventricular and coronary vascular hypertrophy and
      fibrosis, as well as immunohistochemistry analyses of myocardial expression of
      AT1R. l-NAME treatment reduced the plasma nitrate level and led to the
      development of hypertension, with increased plasma levels of AT II and increased
      heart transcriptional levels of AT1R and TGF-beta1-mediated connective tissue
      proteins, showing myocardial and coronary arteriolar hypertrophy and fibrosis.
      However, dietary nitrite supplementation inhibited TGF-beta1-mediated cardiac
      remodeling by suppressing AT II and AT1R. These results suggest that dietary
      nitrite levels achievable via a daily high-vegetable diet could improve
      hypertensive heart disease by inhibiting AT II-AT1R-mediated cardiac remodeling.

PMID- 28438688
TI  - Hepatitis B virus reactivation during hepatitis C direct-acting antiviral therapy
      in patients with previous HBV infection.

PMID- 28438689
TI  - Non-coding RNA in hepatocellular carcinoma: Mechanisms, biomarkers and
      therapeutic targets.
AB  - The majority of the human genome is not translated into proteins but can be
      transcribed into RNA. Even though the resulting non-coding RNAs (ncRNAs) do not
      encode for proteins, they contribute to diseases such as cancer. Here, we review
      examples of the functions of ncRNAs in liver cancer and their potential use for
      the detection and treatment of liver cancer.

PMID- 28438690
TI  - Maturation of secreted HCV particles by incorporation of secreted ApoE protects
      from antibodies by enhancing infectivity.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) evades humoral immunity and
      establishes chronic infections. Virus particles circulate in complex with
      lipoproteins facilitating antibody escape. Apolipoprotein E (ApoE) is essential
      for intracellular HCV assembly and for HCV cell entry. We aimed to explore if
      ApoE released from non-infected cells interacts with and modulates secreted HCV
      particles. METHODS: ApoE secreted from non-infected cells was incubated with HCV
      from primary human hepatocytes or Huh-7.5 cells. Co-immunoprecipitation, viral
      infectivity and neutralization experiments were conducted. RESULTS: Physiological
      levels of secreted ApoE (10-60ug/ml) enhanced the infectivity of HCV up to 8-fold
      across all genotypes, which indirectly decreased virus neutralization by
      antibodies targeting E1 or E2 up to 10-fold. Infection enhancement was observed
      for particles produced in primary human hepatocytes and Huh-7.5 cells. Selective
      depletion of ApoE ablated infection enhancement. Addition of HA-tagged ApoE to
      HCV particles permitted co-precipitation of HCV virions. Serum ApoE levels ranged
      between 10-60ug/ml, which is ca 100-fold higher than in Huh-7.5 conditioned cell
      culture fluids. Serum-derived HCV particles carried much higher amounts of ApoE
      than cell culture-derived HCV particles. Serum ApoE levels correlated with
      efficiency of co-precipitation of HCV upon exogenous addition of HA-ApoE. ApoE
      dependent infection enhancement was independent of the hypervariable region 1 and
      SR-B1, but was dependent on heparan sulfate proteoglycans (HSPGs). CONCLUSIONS:
      Physiological quantities of secreted ApoE stimulate HCV infection and increase
      antibody escape, by incorporating into virus particles and enhancing particle
      interactions with cellular HSPGs. Thus, secreted particles undergo ApoE-dependent
      maturation to enhance infectivity and to facilitate evasion from neutralizing
      antibodies. Lay summary: This study shows that HCV particle infectivity is
      remodeled by secreted ApoE after particle release from cells. Fluctuation of the
      availability of ApoE likely influences HCV infectivity, antibody escape and
      transmission.

PMID- 28438691
TI  - Niche separation in flycatcher-like species in the lowland rainforests of
      Malaysia.
AB  - Niche theory suggests that sympatric species reduce interspecific competition
      through segregation of shared resources by adopting different attack manoeuvres.
      However, the fact that flycatcher-like bird species exclusively use the sally
      manoeuvre may thus challenge this view. We studied the foraging ecology of three
      flycatcher-like species (i.e. Paradise-flycatcher Terpsiphone sp., Black-naped
      Monarch Hypothymis azurea, and Rufous-winged Philentoma Philentoma pyrhoptera) in
      the Krau Wildlife Reserve in central Peninsular Malaysia. We investigated
      foraging preferences of each bird species and the potential niche partitioning
      via spatial or behavioural segregation. Foraging substrate was important
      parameter that effectively divided paradise-flycatcher from Black-naped Monarch
      and Rufous-winged Philentoma, where monarch and philentoma foraged mainly on live
      green leaves, while paradise-flycatcher foraged on the air. They also exhibited
      different foraging height preferences. Paradise-flycatcher, for instance,
      preferred the highest studied strata, while Black-naped Monarch foraged mostly in
      lower strata, and Rufous-winged Philentoma made use of the lowest strata. This
      study indicates that niche segregation occurs among sympatric species through
      foraging substrate and attack manoeuvres selection.

PMID- 28438692
TI  - Temporal variation in the operational sex ratio and male mating behaviours in
      reindeer (Rangifer tarandus).
AB  - In polygynous species, sexual selection is mostly driven by male ability to
      monopolize access to females in oestrous. In ungulates, the operational sex ratio
      (OSR), i.e. the proportion of males to individuals ready to mate, varies
      throughout the peak rut, resulting from the temporal variation in the number of
      females in oestrous. But the way males adjust their mating tactics to maximise
      their access to females in oestrous (i.e. as OSR varies) is yet to be
      investigated. Using 15 years of behavioural observations in reindeer (Rangifer
      tarandus), we compared the relative importance of time within the rutting season
      (days to the peak-rut) and the OSR to explain the variation in the propensity
      (i.e. the frequency after controlling for the potential number of encounters) of
      young and adult dominant males to engage in four mating tactics: herding females,
      chasing other males, investigating female reproductive status, and courting
      females. Male-male agonistic behaviour was the most frequent mating behaviour,
      followed by herding. As predicted, dominant male mating tactics changed over the
      rutting season: first herding, then chasing other males, and finally
      investigating and courting females. In contrast to our prediction, we did not
      find support for the OSR theory. We noted some discrepancies in how young and
      adult dominant males adjusted their tactics during the mating season, adults
      being more efficient in timing and in performing their behaviour to maximise
      access to females in oestrous. The reported sequence of mating tactics may be
      more efficient than a static mating tactic to monopolize females in oestrous,
      regardless of the population composition.

PMID- 28438693
TI  - Effects of four novel genetic polymorphisms on clopidogrel efficacy in Chinese
      acute coronary syndromes patients.
AB  - Dual antiplatelet therapy is the gold standard for the clinical treatment of
      coronary artery disease, especially for acute coronary syndromes patients.
      However, a substantial number of patients do not respond to clopidogrel despite a
      standardized dosage regimen, and this is directly associated with poor prognosis.
      Genetic polymorphisms may be one of the most important factors that contribute to
      this phenomenon. In this study, we aimed to detect new single nucleotide
      polymorphisms that can influence the efficacy of clopidogrel in 851 acute
      coronary syndromes (ACS) patients. Four outcomes (cerebrovascular event, Acute
      Myocardium Infarction, unstable angina and death) were used as endpoints among
      three cohorts (northern, central and southern China) of acute coronary syndromes
      patients. Three SNPs (rs2244923, rs2773341 and rs34428341) were significantly
      associated with at least one outcome in all subjects. One SNP rs16863352, may
      play a role in predicting unstable angina in acute coronary syndrome patients
      >=75years of age.

PMID- 28438694
TI  - Predictive role of GSTP1-containing exosomes in chemotherapy-resistant breast
      cancer.
AB  - Anthracycline/taxane-based chemotherapy regimens are usually used as neoadjuvant
      chemotherapies to decrease tumour size and prevent metastasis of advanced breast
      cancer. However, patients have a high risk of developing chemo-resistance during
      treatment through still unknown mechanisms. Glutathione S-transferase P1 (GSTP1),
      which belongs to the family of phase II metabolic enzymes, has been reported to
      function in detoxifying several anti-cancer drugs by conjugating them with
      glutathione. Previous studies have identified GSTP1 as a predictor of prognosis
      and chemo-resistance in breast cancer patients, but the mechanisms governing
      GSTP1-dependent drug resistance are still unclear. We have found that GSTP1
      expression is much higher in adriamycin-resistant cells and their corresponding
      exosomes. The role of GSTP1-containing exosomes in conferring drug resistance was
      analysed through cell apoptosis and immunofluorescence staining assays.
      Furthermore, we analysed 42 cases of paired breast cancer tissues collected
      before and after anthracycline/taxane-based neoadjuvant chemotherapy by
      immunohistochemistry. Higher GSTP1 expression was shown in the progressive
      disease (PD)/stable disease (SD) group than in the partial response (PR)/complete
      response (CR) group both in the samples collected before and after the
      chemotherapy treatment. Interestingly, GSTP1 partly re-localized from the cell
      nucleus to the cytoplasm upon treatment, and similar results were obtained for
      the exosomal marker Tumour susceptibility gene 101 protein (TSG101), which also
      increased in the cytoplasm after chemotherapy. After analysing the serum exosomes
      of 30 patients treated with anthracycline/taxane-based neoadjuvant chemotherapy,
      we discovered that the levels of GSTP1 in exosomes from patients in the PD/SD
      group were significantly higher than those in the PR/CR group. Here, for the
      first time, we investigated a novel role for GSTP1-containing exosomes and their
      capability to transfer drug resistance and evaluated their clinical use in
      predicting chemo-resistance.

PMID- 28438695
TI  - WNT inhibitory factor 1 promoter hypermethylation is an early event during
      gallbladder cancer tumorigenesis that predicts poor survival.
AB  - Gallbladder cancer (GBC) is the most common malignant tumor in the human biliary
      tract, but the lack of a marker for timely diagnosis leads to an extremely poor
      prognosis. In this study, we assessed CpG sites in the WIF-1 promoter using
      bisulfite sequencing PCR and methylation-specific PCR to detect methylation in
      gallbladder cancer and cholecystitis tissues. WIF-1 promoter methylation was
      present in 36 of 50 (72.0%) gallbladder cancers but only 5 of 20 (25.0%)
      cholecystitis tissues (P=0.000<0.05), suggesting that WIF-1 promoter methylation
      might participate in the malignant transformation of cholecystitis into
      gallbladder cancer. WIF-1 methylation was negatively correlated with WIF-1
      protein expression by immunohistochemistry, demonstrating that WIF-1 expression
      is downregulated by promoter hypermethylation. We analyzed the prognosis of 50
      GBC patients with 5years of follow-up. Univariate analysis revealed that patients
      with hypermethylated WIF-1 exhibited worse overall survival than those with
      hypomethylated WIF-1 (chi2=8.137, P=0.004<0.05). Furthermore, multivariate
      analysis revealed that WIF-1 methylation was an independent prognostic factor for
      5-year overall survival (P=0.011). Therefore, WIF-1 methylation is a candidate as
      a marker for early gallbladder cancer diagnosis and prognosis.

PMID- 28438697
TI  - Predicting drug loading in PLA-PEG nanoparticles.
AB  - Polymer nanoparticles present advantageous physical and biopharmaceutical
      properties as drug delivery systems compared to conventional liquid formulations.
      Active pharmaceutical ingredients (APIs) are often hydrophobic, thus not soluble
      in conventional liquid delivery. Encapsulating the drugs in polymer nanoparticles
      can improve their pharmacological and bio-distribution properties, preventing
      rapid clearance from the bloodstream. Such nanoparticles are commonly made of non
      toxic amphiphilic self-assembling block copolymers where the core (poly-[d,l
      lactic acid] or PLA) serves as a reservoir for the API and the external part
      (Poly-(Ethylene-Glycol) or PEG) serves as a stealth corona to avoid capture by
      macrophage. The present study aims to predict the drug affinity for PLA-PEG
      nanoparticles and their effective drug loading using in silico tools in order to
      virtually screen potential drugs for non-covalent encapsulation applications. To
      that end, different simulation methods such as molecular dynamics and Monte-Carlo
      have been used to estimate the binding of actives on model polymer surfaces.
      Initially, the methods and models are validated against a series of pigments
      molecules for which experimental data exist. The drug affinity for the core of
      the nanoparticles is estimated using a Monte-Carlo "docking" method. Drug
      miscibility in the polymer matrix, using the Hildebrand solubility parameter
      (delta), and the solvation free energy of the drug in the PLA polymer model is
      then estimated. Finally, existing published ALogP quantitative structure-property
      relationships (QSPR) are compared to this method. Our results demonstrate that
      adsorption energies modelled by docking atomistic simulations on PLA surfaces
      correlate well with experimental drug loadings, whereas simpler approaches based
      on Hildebrand solubility parameters and Flory-Huggins interaction parameters do
      not. More complex molecular dynamics techniques which use estimation of the
      solvation free energies both in PLA and in water led to satisfactory predictive
      models. In addition, experimental drug loadings and Log P are found to correlate
      well. This work can be used to improve the understanding of drug-polymer
      interactions, a key component to designing better delivery systems.

PMID- 28438698
TI  - Chitosan and hyaluronan coated liposomes for pulmonary administration of
      curcumin.
AB  - Aiming at improving the nebulization performances and lung antioxidant protection
      of curcumin, chitosan or hyaluronan-coated liposomes were prepared and their
      characteristics and performances were compared with that of uncoated liposomes.
      Curcumin loaded liposomes displayed a diameter lower than 100nm, the coating with
      both polymers led to a small increase of vesicle size around 130nm and the zeta
      potential turned to positive values using chitosan while remained negative using
      hyaluronan. Chitosan allowed the formation of more lamellar and stiffer vesicles
      with a higher bilayer thickness (dB~59A) with respect to the uncoated liposomes,
      whereas hyaluronan allowed the interdigitation of the bilayers (dB~47A) due to
      the polymer intercalation between phospholipid head groups resulting in vesicles
      mainly organized in uncorrelated bilayers. Both polymer coatings, especially
      hyaluronan, greatly improved the stability of the vesicles, especially during the
      nebulization process, promoting the deposition of the phytodrug in the furthest
      stages of the impactor in high amount (>=50%). Polymer coated vesicles were
      biocompatible and improved the curcumin ability to protect A549 cells from the
      oxidative stress induced by hydrogen peroxide, restoring healthy conditions (cell
      relative metabolic activity 100%). In particular, a synergic effect of curcumin
      and hyaluronan was observed resulting in a proliferative effect and a subsequent
      further enhancement of cell relative metabolic activity up to 120%.

PMID- 28438696
TI  - Altered temporal lobe white matter lipid ion profiles in an experimental model of
      sporadic Alzheimer's disease.
AB  - BACKGROUND: White matter is an early and important yet under-evaluated target of
      Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like
      growth factor resistance contribute to white matter degeneration because
      corresponding signal transduction pathways maintain oligodendrocyte function and
      survival. METHODS: This study utilized a model of sporadic AD in which adult Long
      Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type
      neurodegeneration. Temporal lobe white matter lipid ion profiles were
      characterized by matrix-assisted laser desorption/ionization-imaging mass
      spectrometry (MALDI-IMS). RESULTS: Although the lipid ion species expressed in
      the i.c. STZ and control groups were virtually identical, i.c. STZ mainly altered
      the abundances of various lipid ions. Correspondingly, the i.c. STZ group was
      distinguished from control by principal component analysis and data bar plots.
      i.c. STZ mainly reduced expression of lipid ions with low m/z's (less than 810)
      as well as the upper range m/z lipids (m/z 964-986), and increased expression of
      lipid ions with m/z's between 888 and 937. Phospholipids were mainly included
      among the clusters inhibited by i.c. STZ, while both sulfatides and phospholipids
      were increased by i.c. STZ. However, Chi-Square analysis demonstrated significant
      i.c. STZ-induced trend reductions in phospholipids and increases in sulfatides
      (P<0.00001). CONCLUSIONS: The i.c. STZ model of sporadic AD is associated with
      broad and sustained abnormalities in temporal lobe white matter lipids. The
      findings suggest that the i.c. STZ model could be used for pre-clinical studies
      to assess therapeutic measures for their ability to restore white matter
      integrity in AD.

PMID- 28438699
TI  - Cryptic diversity in Amazonian frogs: Integrative taxonomy of the genus
      Anomaloglossus (Amphibia: Anura: Aromobatidae) reveals a unique case of
      diversification within the Guiana Shield.
AB  - Lack of resolution on species boundaries and distribution can hamper inferences
      in many fields of biology, notably biogeography and conservation biology. This is
      particularly true in megadiverse and under-surveyed regions such as Amazonia,
      where species richness remains vastly underestimated. Integrative approaches
      using a combination of phenotypic and molecular evidence have proved extremely
      successful in reducing knowledge gaps in species boundaries, especially in animal
      groups displaying high levels of cryptic diversity like amphibians. Here we
      combine molecular data (mitochondrial 16S rRNA and nuclear TYR, POMC, and RAG1)
      from 522 specimens of Anomaloglossus, a frog genus endemic to the Guiana Shield,
      including 16 of the 26 nominal species, with morphometrics, bioacoustics, tadpole
      development mode, and habitat use to evaluate species delineation in two lowlands
      species groups. Molecular data reveal the existence of 18 major mtDNA lineages
      among which only six correspond to described species. Combined with other lines
      of evidence, we confirm the existence of at least 12 Anomaloglossus species in
      the Guiana Shield lowlands. Anomaloglossus appears to be the only amphibian genus
      to have largely diversified within the eastern part of the Guiana Shield. Our
      results also reveal strikingly different phenotypic evolution among lineages.
      Within the A. degranvillei group, one subclade displays acoustic and
      morphological conservatism, while the second subclade displays less molecular
      divergence but clear phenotypic divergence. In the A. stepheni species group, a
      complex evolutionary diversification in tadpole development is observed, notably
      with two closely related lineages each displaying exotrophic and endotrophic
      tadpoles.

PMID- 28438700
TI  - Further consideration on the phylogeny of the Ciliophora: Analyses using both
      mitochondrial and nuclear data with focus on the extremely confused class
      Phyllopharyngea.
AB  - Most ciliate phylogenetic analyses have largely relied on the nuclear small
      subunit ribosome DNA (nSSU-rDNA) locus. However, single locus or multi-loci from
      the same genome or chromosome may not be sufficient enough to elucidate
      phylogenetic relationships among ciliate taxa. Therefore, in addition to nSSU
      rDNA, the mitochondrial small subunit ribosome DNA (mtSSU-rDNA) was applied in
      this study. We expanded the taxon sampling especially within the class
      Phyllopharyngea. Phylogenetic analyses based on nSSU-rDNA and mtSSU-rDNA,
      independently, as well as concatenated were performed and revealed the following:
      (1) mtSSU-rDNA is more variable than nSSU-rDNA, and is better at elucidating
      relationships at lower levels, e.g. intra-/inter-specific or generic
      relationships; (2) the validity of the two genera Mirodysteria and Spirodysteria
      is challenged based on their similar morphology with Dysteria and the analyses
      from both mtSSU-rDNA and nSSU-rDNA; (3) Brooklynella is confirmed to be an
      intermediate taxon between Dysteriidae and Hartmannulidae, and may represent a
      distinct family; (4) Trithigmostoma should remain in Chilodonellidae; (5) the
      separation of Paraspathidium from Litostomatea is supported and it groups with
      prostomateans and plagiopyleans. In summary, results from mtSSU-rDNA corroborated
      those of nSSU-rDNA for highly supported clades, and the mtSSU-rDNA tree with its
      secondary structure gave topologies that could be explained by the morphology;
      therefore it can be useful in some cases towards better resolution of robust
      phylogenies.

PMID- 28438701
TI  - Unique parallel radiations of high-mountainous species of the genus Sedum
      (Crassulaceae) on the continental island of Taiwan.
AB  - We explored the temporal and spatial diversification of the plant genus Sedum L.
      (Crassulaceae) in Taiwan based on molecular analysis of nrITS and cpDNA sequences
      from East Asian Sedum members. Our phylogenetic and ancestral area reconstruction
      analysis showed that Taiwanese Sedum comprised two lineages that independently
      migrated from Japan and Eastern China. Furthermore, the genetic distances among
      species in these two clades were smaller than those of other East Asian Sedum
      clades, and the Taiwanese members of each clade occupy extremely varied habitats
      with similar niches in high-mountain regions. These data indicate that species
      diversification occurred in parallel in the two Taiwanese Sedum lineages, and
      that these parallel radiations could have occurred within the small continental
      island of Taiwan. Moreover, the estimated time of divergence for Taiwanese Sedum
      indicates that the two radiations might have been correlated to the formation of
      mountains in Taiwan during the early Pleistocene. We suggest that these parallel
      radiations may be attributable to the geographical dynamics of Taiwan and
      specific biological features of Sedum that allow them to adapt to new ecological
      niches.

PMID- 28438702
TI  - Global phylogeny and biogeography of the fern genus Ctenitis (Dryopteridaceae),
      with a focus on the Indian Ocean region.
AB  - The diverse and pantropical genus Ctenitis, in the Dryopteridaceae, has been
      largely ignored in phylogenetic studies until now. In this study, we fill in this
      gap by reconstructing the first comprehensive phylogeny of the genus including 53
      species currently recognized in the genus Ctenitis, among which seven species
      formerly were assigned to the genus Pseudotectaria and one to Heterogonium.
      Special emphasis was given to the sampling of species occurring in the African
      Indian Ocean region. The presented results include reconstruction of a
      biogeographic scenario based on estimated divergence times and ancestral area
      reconstruction. Our findings confirm the inclusion, within Ctenitis, of the
      Indian Ocean species formerly placed in Pseudotectaria and Heterogonium. The
      crown group divergence was estimated to date back to the Oligocene or Early
      Miocene. The biogeographical scenario indicates an initial divergence of the
      Asian-Pacific ranges and the neotropical ranges, and a subsequent colonization of
      the Afro-Madagascan region by a lineage with neotropical ancestors. The Afro
      Madagascan lineage splits into a lineage endemic to the Mascarene islands and a
      lineage occurring in Madagascar, the Comoros and Africa. The range expansion
      towards Africa and Madagascar was estimated to date back to the late Miocene,
      whereas the estimated ages for the onset of the diversification of the Mascarene
      diversity is consistent with the ages of these young, volcanic islands. The
      absence of any extant species of Ctenitis with a multi-continental distribution
      range and the rarity of inter-island dispersal and speciation in the Indian Ocean
      region suggest a limited contribution of long distance dispersal to the
      biogeographical history of this fern genus, versus a high contribution of local
      speciation.

PMID- 28438703
TI  - Multilayered membranes with tuned well arrays to be used as regenerative patches.
AB  - : Membranes have been explored as patches in tissue repair and regeneration, most
      of them presenting a flat geometry or a patterned texture at the nano/micrometer
      scale. Herein, a new concept of a flexible membrane featuring well arrays forming
      pore-like environments to accommodate cell culture is proposed. The processing of
      such membranes using polysaccharides is based on the production of multilayers
      using the layer-by-layer methodology over a patterned PDMS substrate. The
      detached multilayered membrane exhibits a layer of open pores at one side and a
      total thickness of 38+/-2.2um. The photolithography technology used to produce
      the molds allows obtaining wells on the final membranes with a tuned shape and
      micro-scale precision. The influence of post-processing procedures over
      chitosan/alginate films with 100 double layers, including crosslinking with
      genipin or fibronectin immobilization, on the adhesion and proliferation of human
      osteoblast-like cells is also investigated. The results suggest that the presence
      of patterned wells affects positively cell adhesion, morphology and
      proliferation. In particular, it is seen that cells colonized preferentially the
      well regions. The geometrical features with micro to sub-millimeter patterned
      wells, together with the nano-scale organization of the polymeric components
      along the thickness of the film will allow to engineer highly versatile
      multilayered membranes exhibiting a pore-like microstructure in just one of the
      sides, that could be adaptable in the regeneration of multiple tissues. STATEMENT
      OF SIGNIFICANCE: Flexible multilayered membranes containing multiple micro
      reservoirs are found as potential regenerative patches. Layer-by-layer (LbL)
      methodology over a featured PDMS substrate is used to produce patterned
      membranes, composed only by natural-based polymers, that can be easily detached
      from the PDMS substrate. The combination of nano-scale control of the polymeric
      organization along the thickness of the chitosan/alginate (CHT/ALG) membranes,
      provided by LbL, together with the geometrical micro-scale features of the
      patterned membranes offers a uniqueness system that allows cells to colonize 3
      dimensionally. This study provides a promising strategy to control cellular
      spatial organization that can face the region of the tissue to regenerate.

PMID- 28438704
TI  - Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and
      sustained highly localized retention in solid tumors: Its utility for local siRNA
      delivery.
AB  - : The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as
      a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or
      HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC),
      intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained
      highly localized retention in the tumors according to near infrared (NIR) imaging
      assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was
      chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups
      (PBS solution or dendrimer complexed with nontherapeutic siRNA against green
      fluorescent protein (siGFP)), G4-FA/siVEGFA showed tumor inhibition effects in
      single-dose and two-dose regimen studies. In particular, two doses of G4
      FA/siVEGFA i.t. administered eight days apart resulted in a more profound
      inhibition of tumor growth, accompanied with significant reduction in
      angiogenesis, as judged by CD31 staining and microvessel counts. Tumor size
      reduction in the two-dose regimen study was ascertained semi-quantitatively by
      live fluorescence imaging of YFP tumors and independently supported antitumor
      effects of G4-FA/siVEGFA. Taken together, G4-FA shows high tumor uptake and
      sustained retention properties, making it a suitable platform for local delivery
      of siRNAs to treat cancers that are readily accessible such as HNSCC. STATEMENT
      OF SIGNIFICANCE: Head and neck squamous cell carcinoma (HNSCC) is the sixth most
      common cancer worldwide and is difficult to transfect for gene therapy. We
      developed folate receptor (FR)-targeted polyamidoamine (PAMAM) dendrimer for
      enhanced delivery of genes to HNSCC and gained in-depth understanding of how gene
      delivery and transfection in head and neck squamous cancer cells can be enhanced
      via FR-targeted PAMAM dendrimers. The results we report here are encouraging and
      present latest advances in using dendrimers for cancer therapies, in particular
      for HNSCC. Our work has demonstrated that localized delivery of FR-targeted PAMAM
      dendrimer G4 complexed with siVEGFA resulted in pronounced tumor suppression in
      an HN12 xenograft tumor model. Tumor suppression was attributed to enhanced tumor
      uptake of siRNA and prolonged nanoparticle retention in the tumor. Taken
      together, G4-FA shows high tumor uptake and sustained highly localized retention
      properties, making it a suitable platform for local delivery of siRNAs to treat
      cancers that are readily accessible such as HNSCC.

PMID- 28438705
TI  - TIGR4 strain causes more severe disease than WU2 strain in a mouse model of
      Streptococcus pneumoniae meningitis: a common pathogenic role for interferon
      gamma.
AB  - Streptococcus pneumoniae (S. pneumoniae) meningitis causes debilitating
      neurological symptoms and acute fatalities in patients, and long-term
      neurological sequelae in some survivors. Current vaccines do not protect against
      all 94 known S. pneumoniae capsular serotypes, many of which are capable of
      causing pneumococcal meningitis (PM). We here compare the pathogenic outcomes of
      two clinically virulent isolates of S. pneumoniae, serotype 3 strain WU2 and
      serotype 4 strain TIGR4, in a murine model of PM. At an identical infectious
      dosage of 103 CFU administered via the intracerebroventricular route,
      significantly greater mortality, interleukin (IL)1beta and IL6 production, and
      blood-brain barrier dysfunction occurred in TIGR4-induced PM compared to PM
      caused by WU2. Higher bacterial counts in the cerebrospinal fluid and
      nitrite/nitrate in serum were observed 40 h post inoculation with TIGR4 compared
      to mice infected with WU2. Similar to our previous findings in WU2 PM, interferon
      gamma was an essential driver of the pathogenesis of TIGR4 PM, suggesting that
      this cytokine may be a common pathogenic agent across a range of pneumococcal
      meningitides and, thus, a potential therapeutic target for intervention.

PMID- 28438706
TI  - Towards generalizable entity-centric clinical coreference resolution.
AB  - OBJECTIVE: This work investigates the problem of clinical coreference resolution
      in a model that explicitly tracks entities, and aims to measure the performance
      of that model in both traditional in-domain train/test splits and cross-domain
      experiments that measure the generalizability of learned models. METHODS: The two
      methods we compare are a baseline mention-pair coreference system that operates
      over pairs of mentions with best-first conflict resolution and a mention
      synchronous system that incrementally builds coreference chains. We develop new
      features that incorporate distributional semantics, discourse features, and
      entity attributes. We use two new coreference datasets with similar annotation
      guidelines - the THYME colon cancer dataset and the DeepPhe breast cancer
      dataset. RESULTS: The mention-synchronous system performs similarly on in-domain
      data but performs much better on new data. Part of speech tag features prove
      superior in feature generalizability experiments over other word representations.
      Our methods show generalization improvement but there is still a performance gap
      when testing in new domains. DISCUSSION: Generalizability of clinical NLP systems
      is important and under-studied, so future work should attempt to perform cross
      domain and cross-institution evaluations and explicitly develop features and
      training regimens that favor generalizability. A performance-optimized version of
      the mention-synchronous system will be included in the open source Apache cTAKES
      software.

PMID- 28438708
TI  - Psychopharmacological modulation of event-related potentials suggests that first
      hand pain and empathy for pain rely on similar opioidergic processes.
AB  - Accumulating evidence suggests that empathy for pain recruits similar neural
      processes as the first-hand experience of pain. The pain-related P2, an event
      related potential component, has been suggested as a reliable indicator of neural
      processes associated with first-hand pain. Recent evidence indicates that placebo
      analgesia modulates this component for both first-hand pain and empathy for pain.
      Moreover, a psychopharmacological study showed that administration of an opioid
      antagonist blocked the effects of placebo analgesia on self-report of both first
      hand pain and empathy for pain. Together, these findings suggest that the opioid
      system plays a similar role during first-hand pain and empathy for pain. However,
      such a conclusion requires evidence showing that neural activity during both
      experiences is similarly affected by psychopharmacological blockage of opioid
      receptors. Here, we measured pain-related P2 amplitudes and self-report in a
      group of participants who first underwent a placebo analgesia induction
      procedure. Then, they received an opioid receptor antagonist known to block the
      previously induced analgesic effects. Self-report showed that blocking opioid
      receptors after the induction of placebo analgesia increased both first-hand pain
      and empathy for pain, replicating previous findings. Importantly, P2 amplitudes
      were also increased during both experiences. Thus, the present findings extend
      models proposing that empathy for pain is partially grounded in first-hand pain
      by suggesting that this also applies to the underlying opioidergic neurochemical
      processes.

PMID- 28438707
TI  - Contributions of the parietal cortex to increased efficiency of planning-based
      action selection.
AB  - Response selection is foundational to adaptive behavior, and considerable
      attention has been devoted to investigating this behavior under conditions in
      which the mapping between stimuli and responses is fixed. Results from prior
      studies implicate the left supramarginal gyrus (SMg), premotor and prefrontal
      cortices, as well as the cerebellum in this essential function. Yet, many goal
      directed motor behaviors have multiple solutions with flexible mappings between
      stimuli and responses whose solutions are believed to involve prospective
      planning. Studies of selection under conditions of flexible mappings also reveal
      involvement of the left SMg, as well as bilateral premotor, superior parietal
      cortex (SPL) and pre-supplementary motor (pre-SMA) cortices, along with the
      cerebellum. This evidence is, however, limited by exclusive reliance on tasks
      that involve selection in the absence of overt action execution and without
      complete control of possible confounding effects related to differences in
      stimulus and response processing demands. Here, we address this limitation
      through use of a novel fMRI repetition suppression (FMRI-RS) paradigm. In our
      prime-probe design, participants select and overtly pantomime manual object
      rotation actions when the relationship between stimuli and responses is either
      flexible (experimental condition) or fixed (control condition). When trials were
      repeated in prime-probe pairs of the experimental condition, we detected
      improvements in performance accompanied by a significant suppression of blood
      oxygen-level dependent (BOLD) responses in: left SMg extending into and along the
      length of the intraparietal sulcus (IPS), right IPS, bilateral caudal superior
      parietal lobule (cSPL), dorsal premotor cortex (dPMC), pre-SMA, and in the
      lateral cerebellum. Further, region-of-interest analyses revealed interaction
      effects of fMRI-RS in the experimental versus control condition within left SMg
      and cerebellum, as well as in bilateral caudal SPL. These efficiency effects
      cannot be attributed to the repetition of stimulus or response processing, but
      instead are planning-specific and generally consistent with earlier findings from
      conventional fMRI investigations. We conclude that repetition-related increases
      in the efficiency of planning-based selection appears to be associated with
      parieto-cerebellar networks.

PMID- 28438709
TI  - Characterization of high-resolution Gradient Echo and Spin Echo EPI for fMRI in
      the human visual cortex at 7T.
AB  - The increased signal-to-noise ratio (SNR) offered by functional Magnetic
      Resonance Imaging (fMRI) at 7T allows the acquisition of functional data at sub
      millimetric spatial resolutions. However, simply reducing partial volume effects
      is not sufficient to precisely localize task-induced activation due to the
      indirect mechanisms that relate brain function and the changes in the measured
      signal. In this work T2* and T2 weighted Echo Planar Imaging (EPI) schemes based
      on Gradient Recalled Echo (GRE) and Spin Echo (SE) were evaluated in terms of
      temporal SNR, percent signal change, contrast to noise ratio (CNR), activation
      volume, and sensitivity and specificity to gray matter. Datasets were acquired
      during visual stimulation at in-plane resolutions ranging between 1.5*1.5mm2 and
      0.75*0.75mm2 targeting the early visual cortex. While similar activation foci
      were obtained in all acquisitions, at in-plane resolutions of 1.0*1.0mm2 and
      larger voxel sizes the T2 weighted contrast of SE-EPI allowed the identification
      of the activation site with better spatial accuracy. However, at sub-millimetric
      resolutions the decrease in temporal SNR significantly hampered the sensitivity
      and the extent of the activation site. On the other hand, high resolution T2*
      weighted data collected with GRE-EPI provided higher CNR and sensitivity,
      benefiting from the decreased physiological and partial volume effects. However,
      spurious activations originating from regions of blood drainage were still
      present in GRE data, and simple thresholding techniques were found to be
      inadequate for the removal of such contributions. The combination of 2-class and
      3-class automated segmentations, performed directly in EPI space, allowed the
      selection of active voxels in gray matter. This approach could enable GRE-EPI to
      accurately map functional activity with satisfactory CNR and specificity to the
      true site of activation.

PMID- 28438710
TI  - A purpose-built neck coil for black-blood DANTE-prepared carotid artery imaging
      at 7T.
AB  - Atherosclerotic plaques in the bifurcation of the carotid arteries can pose a
      significant health risk due to possible plaque rupture and subsequent stroke. The
      assessment of plaques, and evaluation of the risk they pose, can be performed
      with Black-Blood (BB) vessel wall magnetic resonance imaging. However, resolution
      at standard clinical field strengths (up to 3T) is limited, hampering reliable
      assessment and diagnosis. The aim of this study was to investigate the benefits
      of 7T MRI using a BB application that has been successful at clinical field
      strengths. Therefore, for BB imaging, each sequence was preceded with 'Delay
      Alternating with Nutation for Tailored Excitation' (DANTE) preparation pulses for
      blood signal suppression. A coil comprising a 4-channel Tx array was designed and
      built to provide the required excitation coverage for the DANTE train; and a 4
      channel Rx array was constructed to target the carotid bifurcation. Human and
      phantom results showed satisfactory blood suppression and comparable SNR and CNR
      to 3T, therefore demonstrating the feasibility of the application at 7T. However,
      the imposed SAR restrictions led to long scan times and subsequent motion
      artifacts. Thus, more accurate local SAR supervision schemes are required which
      could lead to a further improvement of BB DANTE vessel wall imaging at 7T.

PMID- 28438711
TI  - Can transverse relaxation rates in deep gray matter be approximated from
      functional and T2-weighted FLAIR scans for relative brain iron quantification?
AB  - Alterations in iron concentration in certain deep gray matter regions are known
      to occur in aging and several clinical conditions. In vivo measurements of R2*
      transverse relaxation rates and quantitative susceptibility mapping (QSM) have
      been shown to be strongly correlated with iron concentration in tissue, but their
      calculation requires the acquisition of a multi-echo gradient recalled echo
      sequence (MGRE). In the current study, we examined the feasibility of
      approximating R2* rates using metrics derived from fMRI-EPI and T2-weighted FLAIR
      images, which are widely available. In a sample of 40 healthy subjects, we
      obtained these metrics (vEPI and vFLAIR), as well as R2* rates and QSM estimates,
      and found significant correlations between vEPI and vFLAIR and R2* rates in
      several subcortical gray matter regions known to accumulate iron, but not in a
      control corticospinal white matter region. These relationships were preserved
      after referencing vEPI and vFLAIR with respect to the values in the control
      region. Effect sizes (above 0.5 for some of the regions, particularly the largest
      ones) were calculated and put in relation to those of the correlation between QSM
      and R2* rates. We propose that the metrics described here may be applied,
      possibly in a retrospective fashion, to analyze datasets with available EPI or T2
      weighted FLAIR scans (and lacking a MGRE sequence), to devise new hypotheses
      regarding links between iron concentration in brain tissue and other variables of
      interest.

PMID- 28438712
TI  - Empirical consideration of the effects of acquisition parameters and analysis
      model on clinically feasible q-ball imaging.
AB  - Q-ball imaging (QBI) is a popular high angular resolution diffusion imaging
      (HARDI) technique used to study brain architecture in vivo. Simulation and
      phantom-based studies suggest that QBI results are affected by the b-value, the
      number of diffusion weighting directions, and the signal-to-noise ratio (SNR).
      However, optimal acquisition schemes for QBI in clinical settings are largely
      undetermined given empirical (observed) imaging considerations. In this study, we
      acquire a HARDI dataset at five b-values with 11 repetitions on a single subject
      to investigate the effects of acquisition scheme and subsequent analysis models
      on the accuracy and precision of measures of tissue composition and fiber
      orientation derived from clinically feasible QBI at 3T. Clinical feasibility
      entails short scan protocols - less than 5minutes in the current study -
      resulting in lower SNR, lower b-values, and fewer diffusion directions than are
      typical in most QBI protocols with research applications, where time constraints
      are less prevalent. In agreement with previous studies, we find that the b-value
      and number of diffusion directions impact the magnitude and variation of QBI
      indices in both white matter and gray matter regions; however, QBI indices are
      most heavily dependent on the maximum order of the spherical harmonic (SH) series
      used to represent the diffusion orientation distribution function (ODF).
      Specifically, to ensure numerical stability and reduce the occurrence of false
      peaks and inflated anisotropy, we recommend oversampling by at least 8-12 more
      diffusion directions than the number of estimated coefficients for a given SH
      order. In addition, in an equal scan time comparison of QBI accuracy, we find
      that increasing the directional resolution of the HARDI dataset is preferable to
      repeating observations; however, our results indicate that as few as 32
      directions at a low b-value (1000s/mm2) captures most of the angular information
      in the q-ball ODF. Our findings provide guidance for determining an optimal
      acquisition scheme for QBI in the low SNR and low scan time regime, and suggest
      that care must be taken when choosing the basis functions used to represent the
      QBI ODF.

PMID- 28438713
TI  - Effects of arterial input function selection on kinetic parameters in brain
      dynamic contrast-enhanced MRI.
AB  - PURPOSE: Kinetic parameters derived from dynamic contrast-enhanced MRI (DCE-MRI)
      were suggested as a possible instrument for multi-parametric lesion
      characterization, but have not found their way into clinical practice yet due to
      inconsistent results. The quantification is heavily influenced by the definition
      of an appropriate arterial input functions (AIF). Regarding brain tumor DCE-MRI,
      there are currently several co-existing methods to determine the AIF frequently
      including different brain vessels as sources. This study quantitatively and
      qualitatively analyzes the impact of AIF source selection on kinetic parameters
      derived from commonly selected AIF source vessels compared to a population-based
      AIF model. MATERIAL AND METHODS: 74 patients with brain lesions underwent 3D DCE
      MRI. Kinetic parameters [transfer constants of contrast agent efflux and reflux
      Ktrans and kep and, their ratio, ve, that is used to measure extravascular
      extracellular volume fraction and plasma volume fraction vp] were determined
      using extended Tofts model in 821 ROI from 4 AIF sources [the internal carotid
      artery (ICA), the closest artery to the lesion, the superior sagittal sinus
      (SSS), the population-based Parker model]. The effect of AIF source alteration on
      kinetic parameters was evaluated by tissue type selective intra-class correlation
      (ICC) and capacity to differentiate gliomas by WHO grade [area under the curve
      analysis (AUC)]. RESULTS: Arterial AIF more often led to implausible ve >100%
      values (p<0.0001). AIF source alteration rendered different absolute kinetic
      parameters (p<0.0001), except for kep. ICC between kinetic parameters of
      different AIF sources and tissues were variable (0.08-0.87) and only consistent
      >0.5 between arterial AIF derived kinetic parameters. Differentiation between WHO
      III and II glioma was exclusively possible with vp derived from an AIF in the SSS
      (p=0.03; AUC 0.74). CONCLUSION: The AIF source has a significant impact on
      absolute kinetic parameters in DCE-MRI, which limits the comparability of kinetic
      parameters derived from different AIF sources. The effect is also tissue
      dependent. The SSS appears to be the best choice for AIF source vessel selection
      in brain tumor DCE-MRI as it exclusively allowed for WHO grades II/III and III/IV
      glioma distinction (by vp) and showed the least number of implausible ve values.

PMID- 28438714
TI  - The effect of morphological and microstructural integrity of the corpus callosum
      on cognition, fatigue and depression in mildly disabled MS patients.
AB  - AIM: To assess the value of callosal morphological and microstructural integrity
      in assessing different cognitive domains, fatigue and depression in mildly
      disabled multiple sclerosis (MS) patients. MATERIALS AND METHODS: We assessed 29
      mildly disabled MS patients and 15 healthy controls using 3T magnetic resonance
      images (T1-weighted, FLAIR and DTI) and neuropsychological tests assessing
      different cognitive functions, depression and fatigue. We compared the added
      value of morphological measures (corpus callosum area corrected for total
      intracranial volume, index, circularity and the more detailed thickness profile)
      and diffusion features (fractional anisotropy and mean diffusivity) in
      multilinear models including standard clinical and whole-brain parameters in
      assessing neuropsychological scores. RESULTS: Even in mildly disabled MS
      patients, a significant reduction of the corpus callosum (p<0.001) was observed
      in comparison to healthy controls. Callosal area, index and circularity were
      significantly (p<0.002) related to whole-brain white matter volume, T2 lesion
      load and deep grey matter volume, but not with cortical grey matter. The
      combination of commonly used imaging and clinical parameters explained between 7%
      (Fatigue) and 50% (processing speed, verbal memory) of the adjusted variance.
      Inclusion of the mean diffusivity increased the adjusted R2 significantly to 69%
      (p=0.004) and 71% (p=0.002) for visuospatial and verbal memory respectively.
      CONCLUSION: Our results show that callosal features may be used as an alternative
      to measuring whole-brain volumes. Furthermore, the microstructural integrity of
      the corpus callosum can help to predict an MS patient's memory performance.

PMID- 28438715
TI  - Impact of physical exercise on visceral adipose tissue fatty acid profile and
      inflammation in response to a high-fat diet regimen.
AB  - PURPOSE: Studies associate specific fatty-acids (FA) with the pathophysiology of
      inflammation. We aimed to analyze the impact of exercise on adipose tissue FA
      profile in response to a high-fat diet (HFD) and to ascertain whether these
      exercise-induced changes in specific FA have repercussions on obesity-related
      inflammation. METHODS: Sprague-Dawley rats were assigned into sedentary,
      voluntary physical-activity (VPA) and endurance training (ET) groups fed a
      standard (S, 35kcal% fat) or high-fat (71kcal% fat) diets. VPA-animals had
      unrestricted access to wheel-running. After 9-wks, ET-animals engaged a running
      protocol for 8-wks, while maintained dietary treatments. The FA content in
      epididymal white-adipose tissue (eWAT) triglycerides was analyzed by gas
      chromatography and the expression of inflammatory markers was determined using RT
      qPCR, Western and slot blotting. RESULTS: Eight-wks of ET reversed obesity
      related anatomical features. HFD increased plasma tumor necrosis factor (TNF)
      alpha content and eWAT monocyte chemoattractant protein (MCP)-1 protein
      expression. HFD decreased eWAT content of saturated FA and monounsaturated FA,
      while increased linoleic acid and prostaglandin E2 (PGE2) levels in eWAT. VPA
      decreased visceral adiposity, adipocyte size and MCP-1 in HFD-fed animals. The
      VPA and ET interventions diminished palmitoleic acid and increased linoleic acid
      in HFD-fed groups. Moreover, both interventions increased PGE2 levels in standard
      diet-fed groups and decreased in HFD. ET increased eWAT fatty acid desaturase 1
      (FADS1) and elongase 5 (ELOVL5) protein content in both diet types. ET reduced
      eWAT inflammatory markers (TNF-alpha, IL-6), macrophage recruitment (MCP-1 and
      F4/80) and increased IL-10/TNF-alpha ratio in plasma and in eWAT in both diet
      types. CONCLUSIONS: Exercise induced FA-specific changes independently of dietary
      FA composition, but only ET attenuated the inflammatory response in VAT of HFD
      fed rats. Moreover, the exercise-induced FA changes did not correlate with the
      inflammatory response in VAT of rats submitted to HFD.

PMID- 28438716
TI  - YAP1 negatively regulates chondrocyte differentiation partly by activating the
      beta-catenin signaling pathway.
AB  - YAP1 (Yes-associated protein 1) transcriptional coactivator is a downstream gene
      of the Hippo signaling pathway, which controls cell proliferation and
      differentiation. YAP1 plays a significant role in the regulation of cartilage and
      bone development. However, the molecular mechanism by which YAP1 regulates
      chondrocyte differentiation remains to be elucidated. Immunofluorescent staining
      was used to visualize the localization of YAP1 expression in the mouse
      chondroprogenitor ATDC5 cell line. ATDC5 cells with lentivirus-vector-mediated
      YAP1 overexpression and knockdown were established. The differentiation abilities
      were examined by real-time quantitative PCR and two staining methods The
      expression levels of sex-determining region Y-type high mobility group box
      protein (SOX9) and key proteins in the Wnt/beta-catenin pathway were analyzed by
      Western blot. The Dickkopf-1 (Dkk1) and small interfering RNA (siRNA) of beta
      catenin were used for further study. The YAP1 protein was mainly expressed in the
      nucleus of ATDC5 cells. YAP1 overexpression enhanced chondrocyte proliferation
      but inhibited chondrocyte differentiation, which were contrary to the findings of
      the YAP1-knockdown group. Moreover, YAP1 overexpression activated Wnt/beta
      catenin signaling pathway. Treatment with exogenous DKK1 and beta-catenin siRNA
      partially recaptured the effects of YAP1 overexpression on ATDC5 cell
      differentiation. Taken together, our study suggested that YAP1 attenuated ATDC5
      cell chondrogenic and hypertrophic differentiation. We also demonstrated that
      YAP1 exerted its effect on the chondrocyte differentiation by activating the
      Wnt/beta-catenin signaling pathway.

PMID- 28438717
TI  - Old age = end of the road? Not always!

PMID- 28438718
TI  - The effect of 50% compared to 100% inspired oxygen fraction on brain oxygenation
      and post cardiac arrest mitochondrial function in experimental cardiac arrest.
AB  - BACKGROUND AND AIM: We hypothesised that the use of 50% compared to 100% oxygen
      maintains cerebral oxygenation and ameliorates the disturbance of cardiac
      mitochondrial respiration during cardiopulmonary resuscitation (CPR). METHODS:
      Ventricular fibrillation (VF) was induced electrically in anaesthetised healthy
      adult pigs and left untreated for seven minutes followed by randomisation to
      manual ventilation with 50% or 100% oxygen and mechanical chest compressions
      (LUCAS(r)). Defibrillation was performed at thirteen minutes and repeated if
      necessary every two minutes with 1mg intravenous adrenaline. Cerebral oxygenation
      was measured with near-infrared spectroscopy (rSO2, INVOSTM5100C Cerebral
      Oximeter) and with a probe (NEUROVENT-PTO, RAUMEDIC) in the frontal brain cortex
      (PbO2). Heart biopsies were obtained 20min after the return of spontaneous
      circulation (ROSC) with an analysis of mitochondrial respiration (OROBOROS
      Instruments Corp., Innsbruck, Austria), and compared to four control animals
      without VF and CPR. Brain rSO2 and PbO2 were log transformed and analysed with a
      mixed linear model and mitochondrial respiration with an analysis of variance.
      RESULTS: Of the twenty pigs, one had a breach of protocol and was excluded,
      leaving nine pigs in the 50% group and ten in the 100% group. Return of
      spontaneous circulation (ROSC) was achieved in six pigs in the 50% group and
      eight in the 100% group. The rSO2 (p=0.007) was lower with FiO2 50%, but the PbO2
      was not (p=0.93). After ROSC there were significant interactions between time and
      FiO2 regarding both rSO2 (p=0.001) and PbO2 (p=0.004). Compared to the controls,
      mitochondrial respiration was decreased, with adenosine diphosphate (ADP) levels
      of 57 (17)pmols-1mg-1 compared to 92 (23)pmols-1mg-1 (p=0.008), but there was no
      difference between different oxygen fractions (p=0.79). CONCLUSIONS: The use of
      50% oxygen during CPR results in lower cerebral oximetry values compared to 100%
      oxygen but there is no difference in brain tissue oxygen. Cardiac arrest disturbs
      cardiac mitochondrial respiration, but it is not alleviated with the use of 50%
      compared to 100% oxygen (Ethical and hospital approvals ESAVI/1077/04.10.07/2016
      and HUS/215/2016, S7 30.3.2016, Funding Helsinki University and others).

PMID- 28438719
TI  - Chick subcutaneous and abdominal adipose tissue depots respond differently in
      lipolytic and adipogenic activity to alpha-melanocyte stimulating hormone (alpha
      MSH).
AB  - In birds, alpha-MSH is anorexigenic, but effects on adipose tissue are unknown.
      Four day-old chicks were intraperitoneally injected with 0 (vehicle), 5, 10, or
      50MUg of alpha-MSH and subcutaneous and abdominal adipose tissue collected at
      60min for RNA isolation (n=10). Plasma was collected post-euthanasia at 60 and
      180min for measuring non-esterified fatty acids (NEFA) and alpha-MSH (n=10).
      Relative to the vehicle, food intake was reduced in the 50MUg-treated group.
      Plasma NEFAs were greater in 10MUg than vehicle-treated chicks at 3h. Plasma
      alpha-MSH was 3.06+/-0.57ng/ml. In subcutaneous tissue, melanocortin receptor 5
      (MC5R) mRNA was increased in 10MUg, MC2R and CCAAT-enhancer-binding protein beta
      (C/EBPbeta) mRNAs increased in 50MUg, peroxisome proliferator-activated receptor
      gamma and C/EBPalpha decreased in 5, 10 and 50MUg, and Ki67 mRNA decreased in
      50MUg alpha-MSH-injected chicks, compared to vehicle-injected chicks. In
      abdominal tissue, adipose triglyceride lipase mRNA was greater in 10MUg alpha-MSH
      than vehicle-treated chicks. Cells isolated from abdominal fat that were treated
      with 10 and 100nM alpha-MSH for 4h expressed more MC5R and perilipin-1 than
      control cells (n=6). Cells that received 100nM alpha-MSH expressed more fatty
      acid binding protein 4 and comparative gene identification-58 mRNA than control
      cells. Glycerol-3-phosphate dehydrogenase (G3PDH) activity was greater in cells
      at 9days post-differentiation that were treated with 1 and 100nM alpha-MSH for 4h
      than in control cells (n=3). Results suggest that alpha-MSH increases lipolysis
      and reduces adipogenesis in adipose tissue.

PMID- 28438720
TI  - Sympathetic neural recording-It is all in the details.

PMID- 28438721
TI  - Clinical profile and mutation spectrum of long QT syndrome in Saudi Arabia: The
      impact of consanguinity.
AB  - BACKGROUND: Congenital long QT syndrome (LQTS) is an inherited, potentially fatal
      arrhythmogenic disorder. At least 16 genes have been implicated in LQTS; the
      yield of genetic analysis of 3 genes (KCNQ1, KCNH2, and SCN5A) is about 70%, with
      KCNQ1 mutations accounting for ~50% of positive cases. LQTS is mostly inherited
      in an autosomal dominant pattern. Systemic analysis of LQTS has not been
      previously conducted in a population with a high degree of consanguinity.
      OBJECTIVES: To describe the clinical and molecular profiles of LQTS in the highly
      consanguineous Saudi population. METHODS: Fifty-six Saudi families with LQTS were
      consecutively recruited and evaluated. Sequencing of KCNQ1, KCNH2, and SCN5A
      genes was conducted on all probands, followed by screening of family relatives.
      RESULTS: Genetic analysis was positive in 32 (57.2%) families, with mutations in
      KCNQ1 identified in 28 families (50%). Surprisingly, 17 (53.1%) probands were
      segregating homozygous mutations. Family screening identified 123 individuals
      with mutations; 89 (72.4%) were heterozygous, 23 (18.7%) were homozygous, and 11
      (8.9%) were compound heterozygous. Compared to heterozygous, the phenotype was
      more severe in homozygous individuals, with cardiac symptoms in 78.3% (vs 12.4%),
      family history of sudden death in 64.7% (vs 44.4%), and prolonged QT interval in
      100% (vs 43.8%). Congenital deafness was found in 11 (47.8%) homozygous probands.
      CONCLUSION: Our study provides insight into the clinical and molecular profiles
      of LQTS in a consanguineous population. It underscores the importance of
      preemptive management in homozygous patients with LQTS and the value of clinical
      and molecular screening of at-risk relatives.

PMID- 28438722
TI  - Propagation of meandering rotors surrounded by areas of high dominant frequency
      in persistent atrial fibrillation.
AB  - BACKGROUND: Identification of arrhythmogenic regions remains a challenge in
      persistent atrial fibrillation (persAF). Frequency and phase analysis allows
      identification of potential ablation targets. OBJECTIVE: This study aimed to
      investigate the spatiotemporal association between dominant frequency (DF) and
      reentrant phase activation areas. METHODS: A total of 8 persAF patients
      undergoing first-time catheter ablation procedure were enrolled. A noncontact
      array catheter was deployed into the left atrium (LA) and 2048 atrial
      fibrillation electrograms (AEGs) were acquired for 15 seconds following
      ventricular far-field cancellation. DF and phase singularity (PS) points were
      identified from the AEGs and tracked over consecutive frames. The spatiotemporal
      correlation of high DF areas and PS points was investigated, and the organization
      index at the core of high-DF areas was compared with that of their periphery.
      RESULTS: The phase maps presented multiple simultaneous PS points that drift over
      the LA, with preferential locations. Regions displaying higher PS concentration
      showed a degree of colocalization with DF sites, with PS and DF regions being
      neighbors in 61.8% and with PS and DF regions overlapping in 36.8% of the time
      windows. Sites with highest DF showed a greater degree of organization at their
      core compared with their periphery. After ablation, the PS incidence reduced over
      the entire LA (36.2% +/- 23.2%, P < .05), but especially at the pulmonary veins
      (78.6% +/- 22.2%, P < .05). CONCLUSION: Multiple PS points drifting over the LA
      were identified with their clusters correlating spatially with the DF regions.
      After pulmonary vein isolation, the PS's complexity was reduced, which supports
      the notion that PS sites represent areas of relevance to the atrial substrate.

PMID- 28438723
TI  - Long-term outcomes of minimally invasive surgical ablation for atrial
      fibrillation: A single-center experience.
AB  - BACKGROUND: Minimally invasive surgical atrial fibrillation (AF) ablation (MISAA)
      delivers radiofrequency energy via a thoracoscopic approach to perform pulmonary
      vein isolation and left atrial ganglionic plexi ablation. Data on long-term
      outcomes of MISAA are lacking. OBJECTIVE: We report 5-year follow-up data from a
      prospective cohort of patients who underwent MISAA at a single center. METHODS:
      One hundred nine consecutive patients (60 paroxysmal, 49 persistent; mean age
      62.7 +/- 9.3 years) underwent MISAA with left atrial appendage exclusion by a
      single surgeon between 2006 and 2012. Patients were followed with transtelephonic
      monitoring at 1, 6, and 12 months and annually thereafter for up to 5 years.
      Recurrence was defined as any atrial tachyarrhythmia lasting >=30 seconds from 90
      days after surgery onward. RESULTS: Mean follow-up duration was 1738.5 +/- 661.5
      days. Single-procedure success rate was 38% (37 of 98 patients). Atrial
      arrhythmias occurred in 22%, 42%, 55%, 59%, and 62% of patients by 1, 2, 3, 4,
      and 5 years. Seventy-eight (79.6%) patients remained AF free with or without
      additional interventions including catheter ablation, antiarrhythmic drugs, or
      cardioversion. There was no significant difference in AF-free survival between
      paroxysmal and persistent AF groups (P = .725). Multivariate analyses showed
      hypertension to be a significant predictor of AF recurrence (odds ratio 6.6,
      confidence interval 1.41-30.80; P = .016). Five (5.1%) patients had a stroke or
      transient ischemic attack during follow-up. CONCLUSION: AF-free survival was 38%
      at 5 years after MISAA. A total of 79.6% of patients remained AF free with or
      without additional intervention. Patients may have an ongoing risk of stroke even
      in the absence of AF recurrences.

PMID- 28438724
TI  - Toward a More Usable Home-Based Video Telemedicine System: A Heuristic Evaluation
      of the Clinician User Interfaces of Home-Based Video Telemedicine Systems.
AB  - BACKGROUND: Telemedicine is the use of technology to provide and support health
      care when distance separates the clinical service and the patient. Home-based
      telemedicine systems involve the use of such technology for medical support and
      care connecting the patient from the comfort of their homes with the clinician.
      In order for such a system to be used extensively, it is necessary to understand
      not only the issues faced by the patients in using them but also the clinician.
      OBJECTIVES: The aim of this study was to conduct a heuristic evaluation of 4
      telemedicine software platforms-Doxy.me, Polycom, Vidyo, and VSee-to assess
      possible problems and limitations that could affect the usability of the system
      from the clinician's perspective. METHODS: It was found that 5 experts
      individually evaluated all four systems using Nielsen's list of heuristics,
      classifying the issues based on a severity rating scale. RESULTS: A total of 46
      unique problems were identified by the experts. The heuristics most frequently
      violated were visibility of system status and Error prevention amounting to 24%
      (11/46 issues) each. Esthetic and minimalist design was second contributing to
      13% (6/46 issues) of the total errors. CONCLUSIONS: Heuristic evaluation coupled
      with a severity rating scale was found to be an effective method for identifying
      problems with the systems. Prioritization of these problems based on the rating
      provides a good starting point for resolving the issues affecting these
      platforms. There is a need for better transparency and a more streamlined
      approach for how physicians use telemedicine systems. Visibility of the system
      status and speaking the users' language are keys for achieving this.

PMID- 28438725
TI  - Analyzing and Predicting User Participations in Online Health Communities: A
      Social Support Perspective.
AB  - BACKGROUND: Online health communities (OHCs) have become a major source of social
      support for people with health problems. Members of OHCs interact online with
      similar peers to seek, receive, and provide different types of social support,
      such as informational support, emotional support, and companionship. As active
      participations in an OHC are beneficial to both the OHC and its users, it is
      important to understand factors related to users' participations and predict user
      churn for user retention efforts. OBJECTIVE: This study aimed to analyze OHC
      users' Web-based interactions, reveal which types of social support activities
      are related to users' participation, and predict whether and when a user will
      churn from the OHC. METHODS: We collected a large-scale dataset from a popular
      OHC for cancer survivors. We used text mining techniques to decide what kinds of
      social support each post contained. We illustrated how we built text classifiers
      for 5 different social support categories: seeking informational support (SIS),
      providing informational support (PIS), seeking emotional support (SES), providing
      emotional support (PES), and companionship (COM). We conducted survival analysis
      to identify types of social support related to users' continued participation.
      Using supervised machine learning methods, we developed a predictive model for
      user churn. RESULTS: Users' behaviors to PIS, SES, and COM had hazard ratios
      significantly lower than 1 (0.948, 0.972, and 0.919, respectively) and were
      indicative of continued participations in the OHC. The churn prediction model
      based on social support activities offers accurate predictions on whether and
      when a user will leave the OHC. CONCLUSIONS: Detecting different types of social
      support activities via text mining contributes to better understanding and
      prediction of users' participations in an OHC. The outcome of this study can help
      the management and design of a sustainable OHC via more proactive and effective
      user retention strategies.

PMID- 28438726
TI  - Analyzing Unstructured Communication in a Computer-Mediated Environment for
      Adults With Type 2 Diabetes: A Research Protocol.
AB  - BACKGROUND: Individuals with type 2 diabetes have an increased risk for
      comorbidities such as heart disease, lower limb amputations, stroke, and renal
      failure. Multiple factors influence development of complications in a person
      living with type 2 diabetes; however, an individual's self-management behaviors
      may delay the onset of, or lessen the severity of, these complications. Social
      support provides personal, informal advice and knowledge that helps individuals
      initiate and sustain self-management and adherence. OBJECTIVE: Our aim was to
      gain an understanding of type 2 diabetes social interaction in a virtual
      environment, one type of computer-mediated environment (CME), and the social
      support characteristics that increase and sustain self-management in adults
      living with chronic illness. METHODS: This study is a secondary analysis of
      longitudinal data collected in a CME study, Second Life Impacts Diabetes
      Education & Self-Management (1R21-LM010727-01). This virtual environment
      replicated a real-life community where 6 months of naturalistic synchronous voice
      conversations, emails, and text chats were recorded among participants and
      providers. This analysis uses a mixed-methods approach to explore and compare
      qualitative and quantitative findings. This analysis is guided by two theories:
      Strong/Weak Ties Theory and Social Penetration Theory. Qualitative data will be
      analyzed using content analysis, and we will complete descriptive statistics on
      the quantified variables (eg, average number of ties). Institutional review board
      approval was obtained in June 2016. RESULTS: This study is in progress.
      CONCLUSIONS: Interventions provided through virtual environments are a promising
      solution to increasing self-management practices. However, little is known of the
      depth, breadth, and quality of social support that is exchanged and how
      interaction supports self-management and relates to health outcomes. This study
      will provide knowledge that will help guide clinical practice and policy to
      enhance social support for chronic illness via the Internet.

PMID- 28438727
TI  - Influence of Telecommunication Modality, Internet Transmission Quality, and
      Accessories on Speech Perception in Cochlear Implant Users.
AB  - BACKGROUND: Telecommunication is limited or even impossible for more than one
      thirds of all cochlear implant (CI) users. OBJECTIVE: We sought therefore to
      study the impact of voice quality on speech perception with voice over Internet
      protocol (VoIP) under real and adverse network conditions. METHODS: Telephone
      speech perception was assessed in 19 CI users (15-69 years, average 42 years),
      using the German HSM (Hochmair-Schulz-Moser) sentence test comparing Skype and
      conventional telephone (public switched telephone networks, PSTN) transmission
      using a personal computer (PC) and a digital enhanced cordless telecommunications
      (DECT) telephone dual device. Five different Internet transmission quality modes
      and four accessories (PC speakers, headphones, 3.5 mm jack audio cable, and
      induction loop) were compared. As a secondary outcome, the subjective perceived
      voice quality was assessed using the mean opinion score (MOS). RESULTS: Speech
      telephone perception was significantly better (median 91.6%, P<.001) with Skype
      compared with PSTN (median 42.5%) under optimal conditions. Skype calls under
      adverse network conditions (data packet loss > 15%) were not superior to
      conventional telephony. In addition, there were no significant differences
      between the tested accessories (P>.05) using a PC. Coupling a Skype DECT phone
      device with an audio cable to the CI, however, resulted in higher speech
      perception (median 65%) and subjective MOS scores (3.2) than using PSTN (median
      7.5%, P<.001). CONCLUSIONS: Skype calls significantly improve speech perception
      for CI users compared with conventional telephony under real network conditions.
      Listening accessories do not further improve listening experience. Current Skype
      DECT telephone devices do not fully offer technical advantages in voice quality.

PMID- 28438728
TI  - Designing Patient-Centered Text Messaging Interventions for Increasing Physical
      Activity Among Participants With Type 2 Diabetes: Qualitative Results From the
      Text to Move Intervention.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a disease affecting approximately
      29.1 million people in the United States, and an additional 86 million adults
      have prediabetes. Diabetes self-management education, a complex health
      intervention composed of 7 behaviors, is effective at improving self-care
      behaviors and glycemic control. Studies have employed text messages for
      education, reminders, and motivational messaging that can serve as "cues to
      action," aiming to improve glucose monitoring, self-care behaviors, appointment
      attendance, and medication adherence. OBJECTIVES: The Text to Move (TTM) study
      was a 6-month 2-parallel group randomized controlled trial of individuals with
      T2DM to increase physical activity, measured by a pedometer. The intervention arm
      received text messages twice daily for 6 months that were tailored to the
      participant's stage of behavior change as defined by the transtheoretical model
      of behavior change. METHODS: We assessed participants' attitudes regarding their
      experience with text messaging, focusing on perceived barriers and facilitators,
      through two focus groups and telephone interviews. All interviews were
      audiorecorded, transcribed verbatim, coded, and analyzed using a grounded theory
      approach. RESULTS: The response rate was 67% (31/46 participants). The average
      age was 51.4 years and 61% (19/31 participants) were male. The majority of
      individuals were English speakers and married, had completed at least 12th grade
      and approximately half of the participants were employed full-time. Overall,
      participants were satisfied with the TTM program and recalled the text messages
      as educational, informational, and motivational. Program involvement increased
      the sense of connection with their health care center. The wearing of pedometers
      and daily step count information served as motivational reminders and created a
      sense of accountability through the sentinel effect. However, there was
      frustration concerning the automation of the text message program, including the
      repetitiveness, predictability of text time delivery, and lack of customization
      and interactivity of text message content. Participants recommended
      personalization of texting frequency as well as more contact time with personnel
      for a stronger sense of support, including greater surveillance and feedback
      based on their own results and comparison to other participants. CONCLUSIONS:
      Participants in a theory-based text messaging intervention identified key
      facilitators and barriers to program efficacy that should be incorporated into
      future texting interventions to optimize participant satisfaction and outcomes.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT01569243;
      http://clinicaltrials.gov/ct2/show/NCT01569243 (Archived by Webcite at
      http://www.webcitation.org/6pfH6yXag).

PMID- 28438729
TI  - Gathering Opinions on Depression Information Needs and Preferences: Samples and
      Opinions in Clinic Versus Web-Based Surveys.
AB  - BACKGROUND: There has been limited research on the information needs and
      preferences of the public concerning treatment for depression. Very little
      research is available comparing samples and opinions when recruitment for surveys
      is done over the Web as opposed to a personal invitation to complete a paper
      survey. OBJECTIVE: This study aimed to (1) to explore information needs and
      preferences among members of the public and (2) compare Clinic and Web samples on
      sample characteristics and survey findings. METHODS: Web survey participants were
      recruited with a notice on three self-help association websites (N=280). Clinic
      survey participants were recruited by a research assistant in the waiting rooms
      of a family medicine clinic and a walk-in medical clinic (N=238) and completed a
      paper version of the survey. RESULTS: The Clinic and Web samples were similar in
      age (39.0 years, SD 13.9 vs 40.2 years, SD 12.5, respectively), education, and
      proportion in full time employment. The Clinic sample was more diverse in
      demographic characteristics and closer to the demographic characteristics of the
      region (Winnipeg, Canada) with a higher proportion of males (102/238 [42.9%] vs
      45/280 [16.1%]) and nonwhites (Aboriginal, Asian, and black) (69/238 [29.0%] vs
      39/280 [13.9%]). The Web sample reported a higher level of emotional distress and
      had more previous psychological (224/280 [80.0%] vs 83/238 [34.9%]) and
      pharmacological (202/280 [72.1%] vs 57/238 [23.9%]) treatment. In terms of
      opinions, most respondents in both settings saw information on a wide range of
      topics around depression treatment as very important including information about
      treatment choices, effectiveness of treatment, how long it takes treatment to
      work, how long treatment continues, what happens when treatment stops, advantages
      and disadvantages of treatments, and potential side effects. Females, respondents
      with a white background, and those who had received or felt they would have
      benefited from therapy in the past saw more information topics as very important.
      Those who had received or thought they would have benefited in the past from
      medication treatment saw fewer topics as important. Participants in both groups
      expressed an interest in receiving information through discussion with a
      counselor or a physician, through written brochures, or through a recommended
      website. CONCLUSIONS: The recruitment strategies were helpful in obtaining
      opinions from members of the public with different concerns and perspectives, and
      the results from the two methods were complementary. Persons coping with
      emotional distress and individuals not specifically seeking help for depression
      would be interested in information to answer a wide range of important questions
      about depression treatment. The Clinic sample yielded more cultural diversity
      that is a closer match to the population. The Web sample was less costly to
      recruit and included persons who were most interested in receiving information.

PMID- 28438731
TI  - The rise of private medicine in South Asia.

PMID- 28438732
TI  - Marital History and Survival After Stroke.

PMID- 28438733
TI  - Use and Customization of Risk Scores for Predicting Cardiovascular Events Using
      Electronic Health Record Data.
AB  - BACKGROUND: Clinicians who are using the Framingham Risk Score (FRS) or the
      American College of Cardiology/American Heart Association Pooled Cohort Equations
      (PCE) to estimate risk for their patients based on electronic health data (EHD)
      face 4 questions. (1) Do published risk scores applied to EHD yield accurate
      estimates of cardiovascular risk? (2) Are FRS risk estimates, which are based on
      data that are up to 45 years old, valid for a contemporary patient population
      seeking routine care? (3) Do the PCE make the FRS obsolete? (4) Does refitting
      the risk score using EHD improve the accuracy of risk estimates? METHODS AND
      RESULTS: Data were extracted from the EHD of 84 116 adults aged 40 to 79 years
      who received care at a large healthcare delivery and insurance organization
      between 2001 and 2011. We assessed calibration and discrimination for 4 risk
      scores: published versions of FRS and PCE and versions obtained by refitting
      models using a subset of the available EHD. The published FRS was well calibrated
      (calibration statistic K=9.1, miscalibration ranging from 0% to 17% across risk
      groups), but the PCE displayed modest evidence of miscalibration (calibration
      statistic K=43.7, miscalibration from 9% to 31%). Discrimination was similar in
      both models (C-index=0.740 for FRS, 0.747 for PCE). Refitting the published
      models using EHD did not substantially improve calibration or discrimination.
      CONCLUSIONS: We conclude that published cardiovascular risk models can be
      successfully applied to EHD to estimate cardiovascular risk; the FRS remains
      valid and is not obsolete; and model refitting does not meaningfully improve the
      accuracy of risk estimates.

PMID- 28438734
TI  - Total Thrombus-formation Analysis System Predicts Periprocedural Bleeding Events
      in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary
      Intervention.
AB  - BACKGROUND: Periprocedural bleeding events are common after percutaneous coronary
      intervention. We evaluated the association of periprocedural bleeding events with
      thrombogenicity, which was measured quantitatively by the Total Thrombus
      formation Analysis System equipped with microchips and thrombogenic surfaces
      (collagen, platelet chip [PL]; collagen plus tissue factor, atheroma chip [AR]).
      METHODS AND RESULTS: Between August 2013 and March 2016, 313 consecutive patients
      with coronary artery disease undergoing elective percutaneous coronary
      intervention were enrolled. They were divided into those with or without
      periprocedural bleeding events. We determined the bleeding events as composites
      of major bleeding events defined by the International Society on Thrombosis and
      Hemostasis and minor bleeding events (eg, minor hematoma, arteriovenous shunt and
      pseudoaneurysm). Blood samples obtained at percutaneous coronary intervention
      were analyzed for thrombus formation area under the curve (PL24-AUC10 for PL
      chip; AR10-AUC30 for AR chip) by the Total Thrombus-formation Analysis System and
      P2Y12 reaction unit by the VerifyNow system. Periprocedural bleeding events
      occurred in 37 patients. PL24-AUC10 levels were significantly lower in patients
      with such events than those without (P=0.002). Multiple logistic regression
      analyses showed association between low PL24-AUC10 levels and periprocedural
      bleeding events (odds ratio, 2.71 [1.22-5.99]; P=0.01) and association between
      PL24-AUC10 and periprocedural bleeding events in 176 patients of the femoral
      approach group (odds ratio, 2.88 [1.11-7.49]; P=0.03). However, PL24-AUC10 levels
      in 127 patients of the radial approach group were not significantly different in
      patients with or without periprocedural bleeding events. CONCLUSIONS: PL24-AUC10
      measured by the Total Thrombus-formation Analysis System is a potentially useful
      predictor of periprocedural bleeding events in coronary artery disease patients
      undergoing elective percutaneous coronary intervention.

PMID- 28438735
TI  - Comparative Effectiveness and Safety of Dabigatran and Rivaroxaban in Atrial
      Fibrillation Patients.
AB  - BACKGROUND: We aimed to examine the comparative effectiveness and safety between
      dabigatran and rivaroxaban in atrial fibrillation patients. METHODS AND RESULTS:
      We conducted a population-based, retrospective, new-user cohort study based on
      the National Health Insurance claims database in Taiwan. Adult atrial
      fibrillation patients who initiated dabigatran (N=10 625) or rivaroxaban (N=4609)
      between June 1, 2012 and May 31, 2014 were identified as the overall population.
      A propensity score was derived using logistic regression to model the probability
      of receipt of rivaroxaban as a function of potential confounders. Altogether,
      4600 dabigatran users were matched with 4600 rivaroxaban users to create a
      propensity score-matched population. The marginal proportional hazards model was
      applied among the propensity score-matched population as the primary analysis,
      and the proportional hazards model with adjustment of the quintiles of the
      propensity score among the overall population was used as the secondary analysis.
      Rivaroxaban users had a higher risk of all-cause death than dabigatran users
      (hazard ratio 1.44, 95%CI 1.17-1.78 in the primary analysis and hazard ratio
      1.47, 95%CI 1.23-1.75 in the secondary analysis). Rivaroxaban users also
      possessed a higher risk of gastrointestinal hemorrhage needing transfusion than
      dabigatran users in the primary analysis (hazard ratio 1.41, 95%CI 1.02-1.95),
      but the difference diminished in the secondary analysis (hazard ratio 1.20, 95%CI
      0.92-1.56). The risks of ischemic stroke, acute myocardial infarction, arterial
      embolism/thrombosis, and intracranial hemorrhage were similar between the 2
      groups. CONCLUSIONS: Rivaroxaban therapy was associated with a statistically
      significant increase in all-cause death compared with dabigatran therapy in
      atrial fibrillation patients.

PMID- 28438736
TI  - Altered MicroRNA Expression Is Responsible for the Pro-Osteogenic Phenotype of
      Interstitial Cells in Calcified Human Aortic Valves.
AB  - BACKGROUND: The transition of aortic valve interstitial cells (AVICs) to
      myofibroblastic and osteoblast-like phenotypes plays a critical role in calcific
      aortic valve disease progression. Several microRNAs (miRs) are implicated in stem
      cell differentiation into osteoblast. We hypothesized that an epigenetic
      mechanism regulates valvular pro-osteogenic activity. This study examined miR
      profile in AVICs of calcified valves and identified miRs responsible for AVIC
      phenotypic transition. METHODS AND RESULTS: AVICs were isolated from normal and
      diseased valves. The miR microarray analysis revealed 14 upregulated and 12
      downregulated miRs in diseased AVICs. Increased miR-486 and decreased miR-204
      levels were associated with higher levels of myofibroblastic biomarker alpha
      smooth muscle actin and osteoblastic biomarkers runt-related transcription factor
      2 (Runx2) and osterix (Osx). Cotransfection of miR-486 antagomir and miR-204
      mimic in diseased AVICs reduced their ability to express Runx2 and Osx. The miR
      486 mimic upregulated alpha-smooth muscle actin expression in normal AVICs
      through the protein kinase B pathway and moderately elevated Runx2 and Osx
      levels. Knockdown of alpha-smooth muscle actin attenuated Runx2 and Osx
      expression induced by miR-486. The miR-486 mimic and miR-204 antagomir
      synergistically promoted Runx2 and Osx expression and calcium deposition in
      normal AVICs and normal aortic valve tissue. CONCLUSIONS: In AVICs of calcified
      valves, increased levels of miR-486 induce myofibroblastic transition to
      upregulate Runx2 and Osx expression and synergize with miR-204 deficiency to
      elevate cellular and valvular pro-osteogenic activity. These novel findings
      indicate that modulation of the epigenetic mechanism underlying valvular pro
      osteogenic activity has therapeutic potential for prevention of calcific aortic
      valve disease progression.

PMID- 28438737
TI  - Association of Tenofovir Use With Risk of Incident Heart Failure in HIV-Infected
      Patients.
AB  - BACKGROUND: The antiretroviral medication, tenofovir disoproxil fumarate (TDF),
      is used by most human immunodeficiency virus-infected persons in the United
      States despite higher risks of chronic kidney disease. Although chronic kidney
      disease is a strong risk factor for heart failure (HF), the association of TDF
      with incident HF is unclear. METHODS AND RESULTS: We identified 21 435 human
      immunodeficiency virus-infected patients in the United States Veterans Health
      Administration actively using antiretrovirals between 2002 and 2011. We excluded
      patients with a prior diagnosis of HF. TDF was analyzed categorically (current,
      past, or never use) and continuously (per year of use). Proportional hazards
      regression and fully adjusted marginal structural models were used to determine
      the association of TDF exposure with risk of incident HF after adjustment for
      demographic, human immunodeficiency virus-related, and cardiovascular risk
      factors. During follow-up, 438 incident HF events occurred. Unadjusted 5-year
      event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7-1.1),
      1.7 (1.4-2.2), and 4.5 (3.9-5.0), respectively. In fully adjusted analyses, HF
      risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53-0.86) compared
      with never users. Among current TDF users, each additional year of TDF exposure
      was associated with a 21% lower risk of incident HF (95%CI: 0.68-0.92). When
      limited to antiretroviral-naive patients, HF risk remained lower in current TDF
      users (HR=0.53; 95%CI 0.36-0.78) compared to never users. CONCLUSIONS: Among a
      large national cohort of human immunodeficiency virus-infected patients, TDF use
      was strongly associated with lower risk of incident HF. These findings warrant
      confirmation in other populations, both with TDF and the recently approved
      tenofovir alafenamide fumarate.

PMID- 28438738
TI  - Short Length of Stay After Elective Transfemoral Transcatheter Aortic Valve
      Replacement is Not Associated With Increased Early or Late Readmission Risk.
AB  - BACKGROUND: Elderly patients undergoing transcatheter aortic valve replacement
      (TAVR) are at risk of hospital readmission postprocedure. It is not known whether
      the index hospital length of stay and, specifically, early discharge post-TAVR is
      associated with an increased risk of readmission. We hypothesized a nonlinear
      relationship whereby both short and long lengths of stay were associated with
      increased readmission risk. METHODS AND RESULTS: We performed a retrospective
      multicenter cohort analysis of patients undergoing elective transfemoral TAVR and
      surviving to discharge between January 2007 and March 2014. The exposure variable
      was hospital length of stay measured from the procedure date to the date of
      discharge and modeled as a continuous variable in a multivariable cause-specific
      Cox regression. Main outcome measures were 30-day and 1-year all-cause
      readmissions. The study population consisted of 709 patients with a median length
      of stay of 6 days (interquartile range, 4-8). At 30-days and 1-year, 13.5% and
      44.0% of patients were readmitted, respectively. Although post-TAVR length of
      stay was not associated with 30-day all-cause readmissions (P=0.925), there
      existed a significant association with 1-year readmission (P=0.010) after
      adjustment for baseline clinical variables. The association between post-TAVR
      length of stay and 1-year readmission was linear (P=0.549 for nonlinearity) with
      no evidence supporting an increased readmission risk for shorter length of stays.
      CONCLUSIONS: Among elderly survivors of elective transfemoral TAVR, a short
      postprocedural length of stay was not associated with an increased risk
      readmission within 30 days or 1 year. However, the risk of 1-year readmission
      increased with longer post-TAVR lengths of stay.

PMID- 28438739
TI  - Reporting Clinical End Points and Safety Events in an Acute Coronary Syndrome
      Trial: Results With Integrated Collection.
AB  - BACKGROUND: End points and adverse events (AEs) are collected separately in
      clinical trials, yet regulatory requirements for serious AE reporting vary across
      regions, so classifying end points according to seriousness criteria can be
      useful in global trials. METHODS AND RESULTS: In the Apixaban for Prevention of
      Acute Ischemic Events 2 (APPRAISE-2) trial, patients with a recent acute coronary
      syndrome were randomized to apixaban or placebo for the prevention of recurrent
      ischemic events. Suspected end points (myocardial infarction, stroke, or
      bleeding) were adjudicated by an independent clinical events classification
      committee. Safety criteria were collected for suspected end points and AEs.
      Patient-level event rates per 100 patient-days of follow-up, modeled using
      Poisson regression, explored the influence of region and patient characteristics
      on event reporting. Overall, 13 909 events were reported by 858 sites in 39
      countries; 8.4% (n=1166) were suspected end points, and 91.6% (n=12 743) were
      AEs. Overall, 66.0% of suspected end points were confirmed by the clinical events
      classification committee. Most clinical events classification committee-confirmed
      end points met criteria to be classified as serious (94.0%); many clinical events
      classification committee-negated end points also did (63.2%), but fewer AEs met
      seriousness criteria (17.9%). The most common seriousness criterion was
      hospitalization (79.9%, n=2594). Region explained 28.7% of end point- and 26.4%
      of serious AE-reporting variation, and patient characteristics explained an
      additional 25.4% of end point and 13.4% of serious AE variation. Nonserious AE
      reporting variation was not explained by adjustment. CONCLUSIONS: An integrated
      collection of end points and serious AEs is feasible in a multinational trial and
      illustrates the shared characteristics of events. Tailoring event collection to
      fit the phase and purpose of the trial is achievable and informative. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00831441.

PMID- 28438740
TI  - Clinical Significance of Postinfarct Fever in ST-Segment Elevation Myocardial
      Infarction: A Cardiac Magnetic Resonance Imaging Study.
AB  - BACKGROUND: Little is known about causality and pathological mechanism underlying
      association of postinfarct fever with myocardial injury in patients with ST
      segment elevation myocardial infarction. METHODS AND RESULTS: In 276 patients
      undergoing primary percutaneous coronary intervention for ST-segment elevation
      myocardial infarction, cardiac magnetic resonance imaging was performed a median
      of 3.4 days after the index procedure. Forty-five patients had postinfarct fever
      (peak body temperature within 4 days after primary percutaneous coronary
      intervention >=37.7 degrees C; Fever group) whereas 231 did not (no-Fever group).
      Primary outcome was myocardial infarct size as assessed by cardiac magnetic
      resonance imaging. Secondary outcomes were extent of area at risk, myocardial
      salvage index, and microvascular obstruction area. In cardiac magnetic resonance
      imaging analysis, myocardial infarct size (25.6% [19.7-32.4] in the Fever group
      versus 17.2% [11.8-25.4] in the no-Fever group; P<0.01), extent of area at risk
      (43.7% [31.9-54.9] versus 35.3% [24.0-43.7]; P<0.01), and microvascular
      obstruction area (4.4% [0.0-13.2] versus 1.2% [0.0-5.1]; P=0.02) were greater in
      the Fever group than in the no-Fever group. Myocardial salvage index tended to be
      lower in the Fever group compared to the no-Fever group (37.7 [28.5-56.1] versus
      47.0 [34.1-56.8]; P=0.13). In multivariate analysis, postinfarct fever was
      associated with larger myocardial infarct (odds ratio, 3.48; 95% CI, 1.71-7.07;
      P<0.01) and lower MSI (odds ratio, 2.10; 95% CI, 1.01-4.08; P=0.03). CONCLUSIONS:
      Postinfarct fever could predict advanced myocardial injury and less salvaged
      myocardium in ST-segment elevation myocardial infarction patients undergoing
      primary percutaneous coronary intervention.

PMID- 28438742
TI  - Adverse Events as End Points: The Need to Account for Both Sides of the Same
      Coin.

PMID- 28438741
TI  - Maternal Macronutrient Intake and Offspring Blood Pressure 20 Years Later.
AB  - BACKGROUND: Results from 2 cohort studies in Scotland established in the 1940s
      and 1950s (Aberdeen and Motherwell) suggested that a high protein diet during
      pregnancy might adversely influence offspring blood pressure at adult age. Our
      objective was to examine this association in the Danish Fetal Origins Cohort
      (DaFO88). METHODS AND RESULTS: This was a prospective birth cohort of 965 women
      who gave birth in 1988-1989 in Aarhus, Denmark, and whose offspring (n=434)
      participated in a clinical examination ~20 years later. Macronutrient intake was
      assessed in gestational week 30. Multivariable adjusted linear regression was
      used to examine the relation between higher maternal protein intake, at the
      expense of carbohydrates, and offspring blood pressure (isocaloric substitution).
      Main analyses were adjusted for mother's age during pregnancy, prepregnancy body
      mass index, parity, smoking during pregnancy, educational level, and offspring's
      sex. The mean total energy intake was 8.7 MJ/day (SD 2.3 MJ/day). The mean energy
      from carbohydrate, fat, and protein intake was 51, 31, and 16 of total energy,
      respectively. The results showed that after adjustment, higher maternal protein
      intake was associated with slightly higher offspring diastolic blood pressure
      (highest compared with the lowest quintile of protein intake: ?=2.4 mm Hg; 95% CI
      0.4-4.4; P=0.03 for trend). Similar differences, although not significant, were
      found for systolic blood pressure (?=2.6 mm Hg; 95% CI -0.0 to 5.3; P=0.08 for
      trend). CONCLUSIONS: Higher maternal dietary protein intake at the expense of
      carbohydrates was associated with a modest increase in offspring blood pressure
      in young adulthood.

PMID- 28438745
TI  - Management of chronic pain using complementary and integrative medicine.
AB  - Complementary and integrative medicine (CIM) encompasses both Western-style
      medicine and complementary health approaches as a new combined approach to treat
      a variety of clinical conditions. Chronic pain is the leading indication for use
      of CIM, and about 33% of adults and 12% of children in the US have used it in
      this context. Although advances have been made in treatments for chronic pain, it
      remains inadequately controlled for many people. Adverse effects and
      complications of analgesic drugs, such as addiction, kidney failure, and
      gastrointestinal bleeding, also limit their use. CIM offers a multimodality
      treatment approach that can tackle the multidimensional nature of pain with fewer
      or no serious adverse effects. This review focuses on the use of CIM in three
      conditions with a high incidence of chronic pain: back pain, neck pain, and
      rheumatoid arthritis. It summarizes research on the mechanisms of action and
      clinical studies on the efficacy of commonly used CIM modalities such as
      acupuncture, mind-body system, dietary interventions and fasting, and herbal
      medicine and nutrients.

PMID- 28438743
TI  - Implementing Cardiovascular Risk Prediction in Clinical Practice: The Future Is
      Now.

PMID- 28438746
TI  - Police cannot continue to plug gaps in mental health provision, chief inspector
      warns.

PMID- 28438749
TI  - Respiratory difficulty with palatal, laryngeal and respiratory muscle tremor in
      adult-onset Alexander's disease.
AB  - Sleep apnoea and respiratory difficulties are reported in adult-onset Alexander's
      disease (AOAD), an autosomal-dominant leukodystrophy that presents mainly with
      progressive ataxia. We demonstrate for the first time that the respiratory
      symptoms can result from association of palatal tremor with a similar tremor of
      laryngeal and respiratory muscles that interrupts normal inspiration and
      expiration.A 60-year-old woman presented with progressive ataxia, palatal tremor
      and breathlessness. MRI revealed medullary atrophy, bilateral T2 hyperintensities
      in the dentate nuclei and hypertrophic olivary degeneration (HOD). AOAD was
      confirmed genetically with a positive glial fibrillary acidic protein (GFAP)
      mutation. Electrophysiological study revealed 1.5 Hz rhythmic laryngeal and
      respiratory muscle activity. Her respiratory symptoms were significantly improved
      at night with variable positive pressure ventilation.This case illustrates that
      palatal tremor in AOAD, and potentially in other conditions, may be associated
      with treatable breathlessness due to a similar tremor of respiratory muscles.

PMID- 28438747
TI  - Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer's
      disease and Parkinson's disease: Mendelian randomisation study.
AB  - Objective To test the hypothesis that low density lipoprotein (LDL) cholesterol
      due to genetic variation in the genes responsible for LDL cholesterol metabolism
      and biosynthesis(PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR),
      respectively) is associated with a high risk of Alzheimer's disease, vascular
      dementia, any dementia, and Parkinson's disease in the general population.Design
      Mendelian randomisation study.Setting Copenhagen General Population Study and
      Copenhagen City Heart Study.Participants 111 194 individuals from the Danish
      general population.Main outcome measures Risk of Alzheimer's disease, vascular
      dementia, all dementia, and Parkinson's disease.Results In observational
      analyses, the multifactorially adjusted hazard ratio for Parkinson's disease in
      participants with an LDL cholesterol level <1.8 mmol/L versus >=4.0 mmol/L was
      1.70 (95% confidence interval 1.03 to 2.79), whereas the corresponding hazard
      ratios for Alzheimer's disease, vascular dementia, or any dementia did not differ
      from 1.0. PCSK9 and HMGCR variants combined were associated with a 9.3% lower LDL
      cholesterol level. In genetic, causal analyses adjusted for age, sex, and year of
      birth, the risk ratios for a lifelong 1 mmol/L lower LDL cholesterol level were
      0.57 (0.27 to 1.17) for Alzheimer's disease, 0.81 (0.34 to 1.89) for vascular
      dementia, 0.66 (0.34 to 1.26) for any dementia, and 1.02 (0.26 to 4.00) for
      Parkinson's disease. Summary level data from the International Genomics of
      Alzheimer's Project using Egger Mendelian randomisation analysis gave a risk
      ratio for Alzheimer's disease of 0.24 (0.02 to 2.79) for 26 PCSK9 and HMGCR
      variants, and of 0.64 (0.52 to 0.79) for 380 variants of LDL cholesterol level
      lowering.Conclusion Low LDL cholesterol levels due to PCSK9 and HMGCR variants
      had no causal effect on high risk of Alzheimer's disease, vascular dementia, any
      dementia, or Parkinson's disease; however, low LDL cholesterol levels may have a
      causal effect in reducing the risk of Alzheimer's disease.

PMID- 28438750
TI  - Intradiaphragmatic hybrid lesion: surgical decision-making and value of minimal
      invasive surgery.
AB  - Hybrid lesions (HLs) have elements of congenital pulmonary airway malformation
      and extrapulmonary sequestration (EPS) and belong to the congenital lung lesions.
      EPS usually arises in the thorax or the abdomen but rarely in the diaphragm. The
      preoperative diagnostic work-up based on chest radiograph, ultrasound (US) and CT
      often shows imprecise results. Therefore, the exact localisation of the lesion
      can only be ascertained intraoperatively. Here we present a patient, with an
      intradiaphragmatic HL, and demonstrate the difficulties of surgical decision
      making regarding the localisation of the lesion and discuss the value of minimal
      invasive surgery.

PMID- 28438751
TI  - An unusual cause for diffuse pulmonary nodules.

PMID- 28438752
TI  - IgG4-related disease presenting as posterior scleritis and vitritis, progressing
      to multifocal orbital involvement.
AB  - IgG4-related disease (IgG4-RD) is a rare, chronic inflammatory condition that may
      involve nearly every organ system. Originally identified as a cause of autoimmune
      pancreatitis, its characteristic histological and clinical features have been
      found in a wide variety of inflammatory presentations, including the eye and
      orbit. Here we describe an example of a case of IgG4-RD initially presenting as
      scleritis and vitritis, with further progression to multifocal bilateral orbital
      involvement. Tissue biopsy of an orbital mass was highly characteristic of IgG4
      RD histology and a rapid clinical response to corticosteroids was observed. This
      case highlights IgG4-RD as a rare cause of intraocular inflammation that may
      progress to involve the orbit.

PMID- 28438753
TI  - Complicated small bowel diverticular disease: a case series.
AB  - Small bowel diverticulosis of the jejunum and ileum is an uncommon finding with a
      prevalence rate of 0.2% to 1.3% at autopsy and 0.3% to 1.9% on small bowel
      studies. Diagnosis can be difficult because there are no pathognomonic features
      or clinical symptoms that are specific for small bowel diverticulosis. Though
      rare, it is critical to keep the possibility of small bowel diverticulosis in
      mind when evaluating cases of malabsorption, chronic abdominal pain, haemorrhage,
      perforation and intestinal obstruction, especially in patients with connective
      tissue disorders, a family history of diverticula and a personal history of
      colonic diverticulosis. Guidelines for the treatment of complicated small bowel
      diverticulosis are not clearly defined. However, the consensus in treatment is to
      do a small bowel resection with primary anastomosis. We report three interesting
      cases of jejunoileal diverticula that presented in an occult manner and later
      progressed to more emergent manifestations.

PMID- 28438755
TI  - A tenebrous tale: malignant melanoma of the oesophagus.
AB  - A 57-year-old man presented with a 4-month history of worsening symptoms of
      oesophageal obstruction. The physical examination was unremarkable. An
      oesophagogastroduodenoscopy revealed an exophytic tumour in the distal
      oesophagus. A biopsy demonstrated malignant melanoma. Staging of the melanoma
      showed disseminated lymph node and bony-spine metastases. He had no prior history
      of cutaneous or ocular melanoma. Following full multidisciplinary team input, he
      was palliated with a metal mesh stent and immunotherapy. He died 3 months later
      following community management.

PMID- 28438756
TI  - Migration of clips to the colon after laparoscopic partial nephrectomy.
AB  - A 78-year-old man was treated with laparoscopic partial nephrectomy for a 4 cm
      tumour in the lower pole of the left kidney. The patient was discharged 2 days
      postoperatively. Preoperatively there was no sign of metastasis; the pathology
      indicated complete removal of the tumour, a renal cell carcinoma. 53 days
      postoperatively the patient had acute onset of rectal bleeding. A colonoscopy
      revealed necrosis and three clips on the wall of the colon corresponding to where
      the descending colon passes over the left kidney. The patient was treated
      conservatively. Clip migration has been reported previously, but to our knowledge
      we present the first case of clip migration to the colon after laparoscopic
      partial nephrectomy. Suggestions to avoid the presented complication are made.

PMID- 28438754
TI  - Smad1/5 is required for erythropoietin-mediated suppression of hepcidin in mice.
AB  - Anemia suppresses liver hepcidin expression to supply adequate iron for
      erythropoiesis. Erythroferrone mediates hepcidin suppression by anemia, but its
      mechanism of action remains uncertain. The bone morphogenetic protein (BMP)-SMAD
      signaling pathway has a central role in hepcidin transcriptional regulation.
      Here, we explored the contribution of individual receptor-activated SMADs in
      hepcidin regulation and their involvement in erythroferrone suppression of
      hepcidin. In Hep3B cells, SMAD5 or SMAD1 but not SMAD8, knockdown inhibited
      hepcidin (HAMP) messenger RNA (mRNA) expression. Hepatocyte-specific double
      knockout Smad1fl/fl;Smad5fl/fl;Cre+ mice exhibited ~90% transferrin saturation
      and massive liver iron overload, whereas Smad1fl/fl;Smad5fl/wt;Cre+ mice or
      Smad1fl/wt;Smad5fl/fl;Cre+ female mice with 1 functional Smad5 or Smad1 allele
      had modestly increased serum and liver iron, and single-knockout Smad5fl/fl;Cre+
      or Smad1fl/fl;Cre+ mice had minimal to no iron loading, suggesting a gene dosage
      effect. Hamp mRNA was reduced in all Cre+ mouse livers at 12 days and in all Cre+
      primary hepatocytes. However, only double-knockout mice continued to exhibit low
      liver Hamp at 8 weeks and failed to induce Hamp in response to Bmp6 in primary
      hepatocyte cultures. Epoetin alfa (EPO) robustly induced bone marrow
      erythroferrone (Fam132b) mRNA in control and Smad1fl/fl;Smad5fl/fl;Cre+ mice but
      suppressed hepcidin only in control mice. Likewise, erythroferrone failed to
      decrease Hamp mRNA in Smad1fl/fl;Smad5fl/fl;Cre+ primary hepatocytes and
      SMAD1/SMAD5 knockdown Hep3B cells. EPO and erythroferrone reduced liver Smad1/5
      phosphorylation in parallel with Hamp mRNA in control mice and Hep3B cells. Thus,
      Smad1 and Smad5 have overlapping functions to govern hepcidin transcription.
      Moreover, erythropoietin and erythroferrone target Smad1/5 signaling and require
      Smad1/5 to suppress hepcidin expression.

PMID- 28438757
TI  - Malignant middle cerebral artery infarction.

PMID- 28438759
TI  - Palliative care clinicians' knowledge of the law regarding the use of the
      Deprivation of Liberty Safeguards (DoLS).
AB  - OBJECTIVES: To examine palliative care clinicians' level of knowledge of the law
      regarding the use of the Deprivation of Liberty Safeguards (DoLS). METHODS:
      Regional postal survey of palliative care clinicians working in hospices in the
      East of England, undertaken in April 2015. Clinicians' level of knowledge was
      assessed by their response to 7 factual questions. Data regarding self-reported
      levels of confidence in applying the Safeguards was collected, alongside
      information regarding the number of times they had used DoLS in practice. A free
      text section invited additional comments from participants. RESULTS: There were
      47 responses from 14 different organisations; a response rate of 68%. Respondents
      included consultants, specialty and associate specialists, registrars, nurses and
      social workers. Higher self-reported confidence and training in the use of DoLS
      was associated with higher factual knowledge. Consultants had the highest level
      of knowledge, training and experience. Doctors of other grades, nurses and social
      workers recorded less knowledge and experience and scored lower in the knowledge
      sections. The free-text comments revealed difficulty applying the Safeguards in
      practice, particularly among the consultant responses, based around several
      themes: insufficient guidance on how to use the Safeguards, process after death,
      uncertainty as to relevance to palliative care and delays in assessments.
      CONCLUSIONS: Clinicians working in palliative care have good levels of knowledge
      of the DoLS. Despite this concerns were raised, particularly by consultants;
      uncertainty as to when they should be used and the relevance of the Safeguards in
      clinical practice. Further guidance should be given to clinicians working in this
      specialty to ensure that clinical practice is both lawful and in the patients'
      best interests.

PMID- 28438758
TI  - Diabetes mellitus and acquired haemophilia: new association?
AB  - Diabetes mellitus encompasses a group of highly prevalent carbohydrate metabolic
      disorders with an increasing incidence. Some subtypes are thought to be
      associated with other immune-mediated diseases. Acquired haemophilia on the other
      hand is a quite rare autoimmune disease that is thought to be secondary to the
      emergence of inhibiting anticoagulation factor VIII antibodies (inhibitors) in
      patients with previously normal haemostatic function. More recently, numerous
      different diseases have been associated with acquired haemophilia namely immune
      mediated diseases, drugs and solid and haematologic neoplasms. The authors report
      on a case of a patient with new onset acquired haemophilia arising in the setting
      of diabetic ketoacidosis.

PMID- 28438760
TI  - Use of the hyperinsulinemic euglycemic clamp to assess insulin sensitivity in
      guinea pigs: dose response, partitioned glucose metabolism, and species
      comparisons.
AB  - The guinea pig is an alternate small animal model for the study of metabolism,
      including insulin sensitivity. However, only one study to date has reported the
      use of the hyperinsulinemic euglycemic clamp in anesthetized animals in this
      species, and the dose response has not been reported. We therefore characterized
      the dose-response curve for whole body glucose uptake using recombinant human
      insulin in the adult guinea pig. Interspecies comparisons with published data
      showed species differences in maximal whole body responses (guinea pig ~ human <
      rat < mouse) and the insulin concentrations at which half-maximal insulin
      responses occurred (guinea pig > human ~ rat > mouse). In subsequent studies, we
      used concomitant d-[3-3H]glucose infusion to characterize insulin sensitivities
      of whole body glucose uptake, utilization, production, storage, and glycolysis in
      young adult guinea pigs at human insulin doses that produced approximately half
      maximal (7.5 mU.min-1.kg-1) and near-maximal whole body responses (30 mU.min-1.kg
      1). Although human insulin infusion increased rates of glucose utilization (up to
      68%) and storage and, at high concentrations, increased rates of glycolysis in
      females, glucose production was only partially suppressed (~23%), even at high
      insulin doses. Fasting glucose, metabolic clearance of insulin, and rates of
      glucose utilization, storage, and production during insulin stimulation were
      higher in female than in male guinea pigs (P < 0.05), but insulin sensitivity of
      these and whole body glucose uptake did not differ between sexes. This study
      establishes a method for measuring partitioned glucose metabolism in chronically
      catheterized conscious guinea pigs, allowing studies of regulation of insulin
      sensitivity in this species.

PMID- 28438761
TI  - Improved skeletal muscle Ca2+ regulation in vivo following contractions in mice
      overexpressing PGC-1alpha.
AB  - In skeletal muscle, resting intracellular Ca2+ concentration ([Ca2+]i)
      homeostasis is exquisitely regulated by Ca2+ transport across the sarcolemmal,
      mitochondrial, and sarcoplasmic reticulum (SR) membranes. Of these three systems,
      the relative importance of the mitochondria in [Ca2+]i regulation remains poorly
      understood in in vivo skeletal muscle. We tested the hypothesis that the capacity
      for Ca2+ uptake by mitochondria is a primary factor in determining [Ca2+]i
      regulation in muscle at rest and following contractions. Tibialis anterior muscle
      of anesthetized peroxisome proliferator-activated receptor-gamma coactivator
      1alpha (PGC-1alpha)-overexpressing (OE, increased mitochondria model) and wild
      type (WT) littermate mice was exteriorized in vivo and loaded with the
      fluorescent probe fura 2-AM, and Rhod 2-AM Ca2+ buffering and mitochondrial
      [Ca2+] were evaluated at rest and during recovery from fatiguing tetanic
      contractions induced by electrical stimulation (120 s, 100 Hz). In addition, the
      effects of pharmacological inhibition of SR (thapsigargin) and mitochondrial
      [carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP)] function were
      examined at rest. [Ca2+]i in WT remained elevated for the entire postcontraction
      recovery period (+6 +/- 1% at 450 s), but in PGC-1alpha OE [Ca2+]i returned to
      resting baseline within 150 s. Thapsigargin immediately and substantially
      increased resting [Ca2+]i in WT, whereas in PGC-1alpha OE this effect was delayed
      and markedly diminished (WT, +12 +/- 3; PGC-1alpha OE, +1 +/- 2% at 600 s after
      thapsigargin treatment, P < 0.05). FCCP abolished this improvement of [Ca2+]i
      regulation in PGC-1alpha OE. Mitochondrial [Ca2+] accumulation was observed in
      PGC-1alpha OE following contractions and thapsigargin treatment. In the SR, PGC
      1alpha OE downregulated SR Ca2+-ATPase 1 (Ca2+ uptake) and parvalbumin (Ca2+
      buffering) protein levels, whereas mitochondrial Ca2+ uptake-related proteins
      (Mfn1, Mfn2, and mitochondrial Ca2+ uniporter) were upregulated. These data
      demonstrate a heretofore unappreciated role for skeletal muscle mitochondria in
      [Ca2+]i regulation in vivo following fatiguing tetanic contractions and at rest.

PMID- 28438763
TI  - The performing animal: causes and consequences of body remodeling and metabolic
      adjustments in red knots facing contrasting thermal environments.
AB  - Using red knots (Calidris canutus) as a model, we determined how changes in mass
      and metabolic activity of organs relate to temperature-induced variation in
      metabolic performance. In cold-acclimated birds, we expected large muscles and
      heart as well as improved oxidative capacity and lipid transport, and we
      predicted that this would explain variation in maximal thermogenic capacity
      (Msum). We also expected larger digestive and excretory organs in these same
      birds and predicted that this would explain most of the variation in basal
      metabolic rate (BMR). Knots kept at 5 degrees C were 20% heavier and maintained
      1.5 times more body fat than individuals kept in thermoneutral conditions (25
      degrees C). The birds in the cold also had a BMR up to 32% higher and a Msum 16%
      higher than birds at 25 degrees C. Organs were larger in the cold, with muscles
      and heart being 9-20% heavier and digestive and excretory organs being 21-36%
      larger than at thermoneutrality. Rather than the predicted digestive and
      excretory organs, the cold-induced increase in BMR correlated with changes in
      mass of the heart, pectoralis, and carcass. Msum varied positively with the mass
      of the pectoralis, supracoracoideus, and heart, highlighting the importance of
      muscles and cardiac function in cold endurance. Cold-acclimated knots also
      expressed upregulated capacity for lipid transport across mitochondrial membranes
      [carnitine palmitoyl transferase (CPT)] in their pectoralis and leg muscles,
      higher lipid catabolism capacity in their pectoralis muscles [beta-hydroxyacyl
      CoA-dehydrogenase (HOAD)], and elevated oxidative capacity in their liver and
      kidney (citrate synthase). These adjustments may have contributed to BMR through
      changes in metabolic intensity. Positive relationships among Msum, CPT, and HOAD
      in the heart also suggest indirect constraints on thermogenic capacity through
      limited cardiac capacity.

PMID- 28438762
TI  - ETB receptor contribution to vascular dysfunction in postmenopausal women.
AB  - Endothelin-1 (ET-1) contributes to age-related endothelial dysfunction in men via
      the ETA receptor. However, there are sex differences in the ET-1 system, and ETB
      receptors are modulated by sex hormones. The purpose of this study was to test
      the hypothesis that ETB receptors contribute to impaired vasodilatory function in
      postmenopausal women (PMW). We measured flow-mediated dilation (FMD) using
      ultrasound, and cutaneous nitric oxide-mediated vasodilation during local heating
      (42 degrees C) via laser Doppler flowmetry in 18 young women (YW; 22 +/- 1 yr)
      and 16 PMW (56 +/- 1 yr). Cutaneous microdialysis perfusions of lactated Ringer
      (control), an ETB receptor antagonist (BQ-788, 300 nM), and an ETA receptor
      antagonist (BQ-123, 500 nM), were done through separate fibers, followed by
      perfusions of sodium nitroprusside (28 mM) and local heating to 43 degrees C
      (max). Cutaneous vascular conductance (CVC) was calculated as cutaneous blood
      flow/mean arterial pressure and expressed as a percent of maximal dilation. FMD
      (YW: 7.5 +/- 0.5 vs. PMW: 5.6 +/- 0.6%) and cutaneous vasodilation (YW: 93 +/- 2
      vs. PMW: 83 +/- 4%CVCmax) were lower in PMW (both P < 0.05). Blockade of ETB
      receptors decreased cutaneous vasodilation in YW (87 +/- 2%CVCmax; P < 0.05 vs.
      control) but increased vasodilation in PMW (93 +/- 1%CVCmax; P < 0.05 vs.
      control). ETA receptor blockade had minimal effect in YW (92 +/- 1%CVCmax) but
      increased cutaneous vasodilation in PMW (91 +/- 2%CVCmax; P < 0.05 vs. control).
      In conclusion, ETB receptors mediate vasodilation in YW, but this effect is lost
      after menopause. Impaired vasodilatory function in PMW is due in part to a loss
      of ETB-mediated dilation.

PMID- 28438766
TI  - Nurses must be allowed to exercise professional judgment.

PMID- 28438764
TI  - Neurogenic hypertension and the secrets of respiration.
AB  - Despite recent advances in the knowledge of the neural control of cardiovascular
      function, the cause of sympathetic overactivity in neurogenic hypertension
      remains unknown. Studies from our laboratory point out that rats submitted to
      chronic intermittent hypoxia (CIH), an experimental model of neurogenic
      hypertension, present changes in the central respiratory network that impact the
      pattern of sympathetic discharge and the levels of arterial pressure. In addition
      to the fine coordination of respiratory muscle contraction and relaxation, which
      is essential for O2 and CO2 pulmonary exchanges, neurons of the respiratory
      network are connected precisely to the neurons controlling the sympathetic
      activity in the brain stem. This respiratory-sympathetic neuronal interaction
      provides adjustments in the sympathetic outflow to the heart and vasculature
      during each respiratory phase according to the metabolic demands. Herein, we
      report that CIH-induced sympathetic over activity and mild hypertension are
      associated with increased frequency discharge of ventral medullary presympathetic
      neurons. We also describe that their increased frequency discharge is dependent
      on synaptic inputs, mostly from neurons of the brain stem respiratory network,
      rather than changes in their intrinsic electrophysiological properties. In
      perspective, we are taking into consideration the possibility that changes in the
      central respiratory rhythm/pattern generator contribute to increased sympathetic
      outflow and the development of neurogenic hypertension. Our experimental evidence
      provides support for the hypothesis that changes in the coupling of respiratory
      and sympathetic networks might be one of the unrevealed secrets of neurogenic
      hypertension in rats.

PMID- 28438765
TI  - Longitudinal characterization of renal proximal tubular markers in normotensive
      and preeclamptic pregnancies.
AB  - Glomerular damage is common in preeclampsia (PE), but the extent and etiology of
      tubular injury are not well understood. The aim of this study was to evaluate
      tubular injury in patients with PE and to assess whether it predates clinical
      disease. We performed a prospective cohort study of 315 pregnant women who
      provided urine samples at the end of the second trimester and at delivery. This
      analysis included women who developed PE (n = 15), gestational hypertension (GH;
      n = 14), and normotensive controls (NC; n = 44). Urinary markers of tubular
      injury, alpha1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury
      molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP
      2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by
      enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine
      creatinine concentration. Second-trimester concentrations of all markers were
      similar among groups. At delivery, A1M concentrations were higher in the PE group
      than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%,
      respectively, P = 0.01). Concentrations of C5b-9 were higher in the PE group than
      in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, P =
      0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups
      at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and
      C5b-9, developed during the interval between the end of the second trimester and
      delivery in patients with PE. However, this was not matched by abnormalities in
      markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP
      2).

PMID- 28438767
TI  - Face-down restraint has no place in modern mental health settings.

PMID- 28438768
TI  - Thousands march in support of science.

PMID- 28438769
TI  - Authors' reply to Kruger and Large and Ryan.

PMID- 28438770
TI  - Exercise interventions for cognitive function in adults older than 50: a
      systematic review with meta-analysis.
AB  - BACKGROUND: Physical exercise is seen as a promising intervention to prevent or
      delay cognitive decline in individuals aged 50 years and older, yet the evidence
      from reviews is not conclusive. OBJECTIVES: To determine if physical exercise is
      effective in improving cognitive function in this population. DESIGN: Systematic
      review with multilevel meta-analysis. DATA SOURCES: Electronic databases Medline
      (PubMed), EMBASE (Scopus), PsychINFO and CENTRAL (Cochrane) from inception to
      November 2016. ELIGIBILITY CRITERIA: Randomised controlled trials of physical
      exercise interventions in community-dwelling adults older than 50 years, with an
      outcome measure of cognitive function. RESULTS: The search returned 12 820
      records, of which 39 studies were included in the systematic review. Analysis of
      333 dependent effect sizes from 36 studies showed that physical exercise improved
      cognitive function (0.29; 95% CI 0.17 to 0.41; p<0.01). Interventions of aerobic
      exercise, resistance training, multicomponent training and tai chi, all had
      significant point estimates. When exercise prescription was examined, a duration
      of 45-60 min per session and at least moderate intensity, were associated with
      benefits to cognition. The results of the meta-analysis were consistent and
      independent of the cognitive domain tested or the cognitive status of the
      participants. CONCLUSIONS: Physical exercise improved cognitive function in the
      over 50s, regardless of the cognitive status of participants. To improve
      cognitive function, this meta-analysis provides clinicians with evidence to
      recommend that patients obtain both aerobic and resistance exercise of at least
      moderate intensity on as many days of the week as feasible, in line with current
      exercise guidelines.

PMID- 28438771
TI  - Unusual presentation for a tailgut cyst.
AB  - A 67-year-old man with a slow-growing, asymptomatic perianal lesion was presented
      to the colorectal clinic. Physical examination and radiological investigation
      were suggestive of an externally prolapsing colonic polyp. However,
      intraoperative findings of a cystic lesion containing a thick brown substance
      questioned the initial diagnosis. After complete surgical resection of the
      encapsulated lesion, histological examination revealed a tailgut cyst (cystic
      hamartoma). These uncommon lesions originate from an embryological remnant of the
      hindgut. They are generally benign but may have extremely rare malignant
      potential which warrants complete surgical resection. Throughout the literature,
      they are described to present with various symptoms and may be found in several
      anatomical locations, most commonly within the retrorectal space. In very rare
      instances, with only two other documented cases, they can be found externally at
      the anorectal junction. Although very rare, an anal tailgut cyst should be taken
      into account in differential diagnosis.

PMID- 28438772
TI  - Severe vincristine-induced polyneuropathy in a teenager with anaplastic
      medulloblastoma and undiagnosed Charcot-Marie-Tooth disease.
AB  - Severe neuropathy is a known adverse effect of vincristine in patients with
      Charcot-Marie-Tooth disease (CMT). We present the case of a 16-year-old girl with
      anaplastic medulloblastoma treated with gross total resection and high-dose
      craniospinal radiation with adjuvant vincristine chemotherapy who developed acute
      onset severe quadriplegia and vocal cord paralysis. Vincristine and radiation
      therapy were discontinued. Although her neuropathy slowly improved over several
      weeks, she developed metastatic extraneural medulloblastoma and died 5 months
      after diagnosis. Subsequent genetic testing revealed previously asymptomatic and
      undiagnosed CMT1A. Our case highlights the importance of early recognition of
      acute vincristine neurotoxicity that should raise suspicion of an underlying
      hereditary neuropathy.

PMID- 28438773
TI  - Mechanical CPR in a child: can one size fit all?
AB  - This case report describes the successful resuscitation of an 11-year-old boy who
      suffered out-of-hospital cardiac arrest (OHCA) using mechanical cardiopulmonary
      resuscitation (CPR) by adapting the Lund University Cardiopulmonary Assist System
      (LUCAS)2 Device by rolling a blanket under the patient's back to increase his
      chest height, thus allowing the LUCAS device to administer compliant CPR.

PMID- 28438774
TI  - Avelumab Impresses in Merkel Cell Carcinoma.
AB  - The PD-L1 inhibitor avelumab-approved by the FDA in March for the treatment of
      Merkel cell carcinoma-demonstrated a high number of durable responses in an
      international, open-label, prospective phase II study. The results of the study,
      which supported the FDA's decision, were presented in April at the American
      Association for Cancer Research (AACR) Annual Meeting 2017.

PMID- 28438775
TI  - Emergency diagnosis of cancer and previous general practice consultations:
      insights from linked patient survey data.
AB  - BACKGROUND: Emergency diagnosis of cancer is common and aetiologically complex.
      The proportion of emergency presenters who have consulted previously with
      relevant symptoms is uncertain. AIM: To examine how many patients with cancer,
      who were diagnosed as emergencies, have had previous primary care consultations
      with relevant symptoms; and among those, to examine how many had multiple
      consultations. DESIGN AND SETTING: Secondary analysis of patient survey data from
      the 2010 English Cancer Patient Experience Survey (CPES), previously linked to
      population-based data on diagnostic route. METHOD: For emergency presenters with
      18 different cancers, associations were examined for two outcomes (prior GP
      consultation status; and 'three or more consultations' among prior consultees)
      using logistic regression. RESULTS: Among 4647 emergency presenters, 1349 (29%)
      reported no prior consultations, being more common in males (32% versus 25% in
      females, P<0.001), older (44% in >=85 versus 30% in 65-74-year-olds, P<0.001),
      and the most deprived (35% versus 25% least deprived, P = 0.001) patients; and
      highest/lowest for patients with brain cancer (46%) and mesothelioma (13%),
      respectively (P<0.001 for overall variation by cancer site). Among 3298 emergency
      presenters with prior consultations, 1356 (41%) had three or more consultations,
      which were more likely in females (P<0.001), younger (P<0.001), and non-white
      patients (P = 0.017) and those with multiple myeloma, and least likely for
      patients with leukaemia (P<0.001). CONCLUSION: Contrary to suggestions that
      emergency presentations represent missed diagnoses, about one-third of emergency
      presenters (particularly those in older and more deprived groups) have no prior
      GP consultations. Furthermore, only about one-third report multiple (three or
      more) consultations, which are more likely in 'harder-to-suspect' groups.

PMID- 28438776
TI  - The immunoproteasome is induced by cytokines and regulates apoptosis in human
      islets.
AB  - In addition to degrading misfolded and damaged proteins, the proteasome regulates
      the fate of cells in response to stress. The role of the proteasome in pro
      inflammatory cytokine-induced human beta-cell apoptosis is unknown. Using INS-1,
      INS-1E and human islets exposed to combinations of IFNgamma, IL-1beta and
      TNFalpha with or without addition of small molecules, we assessed the role of the
      immunoproteasome in pancreatic beta-cell demise. Here, we show that cytokines
      induce the expression and activity of the immuno-proteasome in INS-1E cells and
      human islets. Cytokine-induced expression of immuno-proteasome subunits, but not
      activity, depended upon histone deacetylase 3 activation. Inhibition of
      JAK1/STAT1 signaling did not affect proteasomal activity. Inhibition of the
      immuno-proteasome subunit PSMB8 aggravated cytokine-induced human beta-cell
      apoptosis while reducing intracellular levels of oxidized proteins in INS-1
      cells. While cytokines increased total cellular NFkappaB subunit P50 and P52
      levels and reduced the cytosolic NFkappaB subunit P65 and IkappaB levels, these
      effects were unaffected by PSMB8 inhibition. We conclude that beta cells
      upregulate immuno-proteasome expression and activity in response to IFNgamma,
      likely as a protective response to confine inflammatory signaling.

PMID- 28438777
TI  - Preference for an Opioid/Benzodiazepine Mixture over an Opioid Alone Using a
      Concurrent Choice Procedure in Rhesus Monkeys.
AB  - Increased abuse of opioids is contributing to an escalation in overdose deaths.
      Benzodiazepines are frequently abused with opioids, possibly because they
      increase the potency and/or effectiveness of opioids to produce reinforcing
      effects. This study used a concurrent-choice procedure to determine whether
      monkeys would choose to self-administer a mixture of the opioid remifentanil and
      the benzodiazepine midazolam over remifentanil alone. Initially, three monkeys
      could respond on one lever for saline and on a second lever for either
      remifentanil alone or midazolam alone. Thereafter, monkeys chose between a dose
      of remifentanil (0.32 ug/kg/infusion) that did not change and a dose of
      remifentanil that varied across sessions; for some sessions, midazolam was
      combined with varying doses of remifentanil. All monkeys received more infusions
      of remifentanil (0.0032-0.32 ug/kg/infusion) than saline, whereas only two
      monkeys responded more for midazolam than for saline. When 0.32 ug/kg/infusion
      remifentanil was available on one lever and a dose of remifentanil that varied
      across sessions (0.1-1 ug/kg/infusion) was available on the other lever, monkeys
      chose the larger dose. Combining 3.2 ug/kg/infusion midazolam with 0.32
      ug/kg/infusion remifentanil increased responding for the mixture over 0.32
      ug/kg/infusion remifentanil alone, although monkeys chose remifentanil alone over
      mixtures containing smaller doses of remifentanil. When 10 ug/kg/infusion
      midazolam was combined with 0.1 ug/kg/infusion remifentanil, monkeys chose the
      mixture over 0.32 ug/kg/infusion remifentanil alone. Thus, monkeys prefer some
      opioid/benzodiazepine mixtures to larger doses of the opioid alone, suggesting
      that opioid/benzodiazepine coabuse might be due to increased potency (and
      possibly effectiveness) of opioids to produce reinforcing effects.

PMID- 28438778
TI  - The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Works as Adjunct to
      Metformin on Fasting Hyperglycemia and HbA1c in a Rat Model of Type 2 Diabetes.
AB  - KBP-042 is a dual amylin and calcitonin receptor agonist that increases glucose
      tolerance and insulin action and reduces body weight in rat models of obesity and
      prediabetes. The objective of the present study was to 1) evaluate KBP-042 as a
      treatment of late-stage type 2 diabetes in a rat model and 2) assess the value of
      adding KBP-042 to the standard of care, metformin, to consider KBP-042 as a
      relevant drug for treating patients with type 2 diabetes. Two studies were
      included: an intervention study and a prevention study. In the intervention
      study, treatment with 5 ug/kg KBP-042 was initiated in 11-week-old Zucker
      diabetic fatty (ZDF) rats, in which glucose tolerance, fasting glycemia, and
      glycated hemoglobin were assessed after 4 weeks. In the prevention study, either
      metformin (400 mg/kg), KBP-042 (5 ug/kg), or a combination of both were
      administered to ZDF rats for a total of 9 weeks. Glycemia, glucose tolerance, and
      insulin tolerance were tested. Furthermore, fasting plasma insulin and glucagon
      levels were evaluated. Finally, pancreatic content of insulin was assessed as a
      surrogate marker of beta-cell mass. It was found that KBP-042 was efficient in
      lowering fasting plasma glucose as well as improving glucose tolerance, both as
      prevention and intervention of disease progression. Furthermore, KBP-042 was
      efficient in combination with metformin and had additional effects compared with
      either therapy alone. In conclusion, KBP-042 is a highly relevant therapeutic
      candidate against type 2 diabetes, effective both as an add-on therapy to
      metformin and as a stand-alone therapy.

PMID- 28438779
TI  - Human Alternative Macrophages Populate Calcified Areas of Atherosclerotic Lesions
      and Display Impaired RANKL-Induced Osteoclastic Bone Resorption Activity.
AB  - RATIONALE: Vascular calcification is a process similar to bone formation leading
      to an inappropriate deposition of calcium phosphate minerals in advanced
      atherosclerotic plaques. Monocyte-derived macrophages, located in atherosclerotic
      lesions and presenting heterogeneous phenotypes, from classical proinflammatory
      M1 to alternative anti-inflammatory M2 macrophages, could potentially display
      osteoclast-like functions. OBJECTIVE: To characterize the phenotype of
      macrophages located in areas surrounding the calcium deposits in human
      atherosclerotic plaques. METHODS AND RESULTS: Macrophages near calcium deposits
      display an alternative phenotype being both CD68 and mannose receptor-positive,
      expressing carbonic anhydrase type II, but relatively low levels of cathepsin K.
      In vitro interleukin-4-polarization of human primary monocytes into macrophages
      results in lower expression and activity of cathepsin K compared with resting
      unpolarized macrophages. Moreover, interleukin-4 polarization lowers expression
      levels of the osteoclast transcriptional activator nuclear factor of activated T
      cells type c-1, associated with increased gene promoter levels of the
      transcriptional repression mark H3K27me3 (histone 3 lysine 27 trimethylation).
      Despite higher expression of the receptor activator of nuclear factor kappaB
      receptor, receptor activator of nuclear factor kappaB ligand/macrophage colony
      stimulating factor induction of nuclear factor of activated T cells type c-1 and
      cathepsin K expression is defective in these macrophages because of reduced Erk/c
      fos-mediated downstream signaling resulting in impaired bone resorption capacity.
      CONCLUSIONS: These results indicate that macrophages surrounding calcium deposits
      in human atherosclerotic plaques are phenotypically defective being unable to
      resorb calcification.

PMID- 28438780
TI  - Penetration Route of the Selective Glucocorticoid Receptor Agonist SA22465 and
      Betamethasone into Rabbit Meibomian Gland Based on Pharmacokinetics and
      Autoradiography.
AB  - Meibomian glands are modified sebaceous glands embedded within specific types of
      dense connective tissues. This study investigated drug penetration into meibomian
      glands following a single topical administration in rabbits. We measured time
      course concentrations of the selective glucocorticoid receptor agonist (SEGRA)
      SA22465 and betamethasone in lid margins, palpebral conjunctival epithelium, and
      meibomian glands following a single instillation using a newly established
      collection method. We also visualized the distribution of 14C-SA22465 in eyelid
      tissue sections using microautoradiography. Concentrations of SA22465 and its
      major metabolite SA22313 were highest in lid margins, followed by palpebral
      conjunctival epithelium and meibomian glands in a 100-fold descending order.
      Betamethasone exhibited similar distribution profiles with smaller concentration
      differences. The distribution of silver grains as a quantitative index of
      radioactivity in eyes and eyelids was determined in a subjective manner using
      microautoradiographs, which revealed that the highest distribution of silver
      grains was associated with the cornea, followed by posterior segment tissues,
      such as the sclera, choroid, and retina. Low levels were associated with more
      internal ocular tissues and a greater number of compartments. Moderate levels of
      radioactivity were associated with meibomian glands and connective tissues,
      including the nictitating membrane. In contrast, meibomian ducts contained only
      background levels of radioactivity. Our findings indicate that the
      transconjunctiva is the most likely route of drug entry into meibomian glands
      following ocular administration rather than the central meibomian duct; however,
      this distribution is limited. A physiologic barrier may restrict drug penetration
      across the tarsal plate.

PMID- 28438781
TI  - Transporter-Mediated Disposition, Clinical Pharmacokinetics and Cholestatic
      Potential of Glyburide and Its Primary Active Metabolites.
AB  - Glyburide is widely used for the treatment of type 2 diabetes. We studied the
      mechanisms involved in the disposition of glyburide and its pharmacologically
      active hydroxy metabolites M1 and M2b and evaluated their clinical
      pharmacokinetics and the potential role in glyburide-induced cholestasis
      employing physiologically based pharmacokinetic (PBPK) modeling. Transport
      studies of parent and metabolites in human hepatocytes and transfected cell
      systems imply hepatic uptake mediated by organic anion-transporting polypeptides.
      Metabolites are also subjected to basolateral and biliary efflux by P
      glycoprotein, breast cancer resistance protein, and multidrug resistance
      associated proteins, and are substrates to renal organic anion transporter 3. A
      PBPK model in combination with a Bayesian approach was developed considering the
      identified disposition mechanisms. The model reasonably described plasma
      concentration time profiles and urinary recoveries of glyburide and the
      metabolites, implying the role of multiple transport processes in their
      pharmacokinetics. Predicted free liver concentrations of the parent (~30-fold)
      and metabolites (~4-fold) were higher than their free plasma concentrations.
      Finally, all three compounds showed bile salt export pump inhibition in vitro;
      however, significant in vivo inhibition was not apparent for any compound on the
      basis of a predicted unbound liver exposure-response effect model using measured
      in vitro IC50 values. In conclusion, this study demonstrates the important role
      of multiple drug transporters in the disposition of glyburide and its active
      metabolites, suggesting that variability in the function of these processes may
      lead to pharmacokinetic variability in the parent and the metabolites,
      potentially translating to pharmacodynamic variability.

PMID- 28438782
TI  - Incidence and prevalence of multiple endocrine neoplasia 2B in Denmark: a
      nationwide study.

PMID- 28438783
TI  - Mistakes and missed opportunities regarding cosmetic surgery and conscientious
      objection.
AB  - In her paper 'Cosmetic surgery and conscientious objection', Minerva rightly
      identifies cosmetic surgery as an interesting test case for the question of
      conscientious objection in medicine. Her treatment of this important subject,
      however, seems problematic. It is argued that Minerva's suggestion that a doctor
      has a prima facie duty to satisfy patient preferences even against his better
      clinical judgment, which we call Patient Preference Absolutism, must be regarded
      with scepticism. This is because (1) it overlooks an important distinction
      regarding autonomy's meaning and place in clinical practice, and (2) it makes
      obsolete the important concepts of expert clinical judgment and beneficence.
      Finally, we discuss two ideas which emerge from consideration of cosmetic surgery
      in relation to conscientious objection. These are the possible analogy between
      clinical judgment and conscientious objection, and the possible role the goals of
      medicine can play in defining the scope of conscientious objection.

PMID- 28438784
TI  - Professional and conscience-based refusals: the case of the psychiatrist's
      harmful prescription.
AB  - By way of a case story, two common presuppositions in the academic debate on
      conscientious objection in healthcare are challenged. First, the debate typically
      presupposes a sharp division between conscience-based refusals based on personal
      core moral beliefs and refusals based on professional (eg, medical) reasons. Only
      the former might involve the moral gravity to warrant accommodation. The case
      story challenges this division, and it is argued that just as much might
      sometimes be at stake morally in refusals based on professional reasons. The
      objector's moral integrity might be equally threatened in objections based on
      professional reasons as in objections based on personal beliefs. Second, the
      literature on conscientious objection typically presupposes that conflicts of
      conscience pertain to well-circumscribed and typical situations which can be
      identified as controversial without attention to individualising features of the
      concrete situation. However, the case shows that conflicts of conscience can
      sometimes be more particular, born from concrete features of the actual
      situation, and difficult, if not impossible, to predict before they arise.
      Guidelines should be updated to address such 'situation-based' conscientious
      refusals explicitly.

PMID- 28438785
TI  - Nuclear receptor research in zebrafish.
AB  - Nuclear receptors (NRs) form a superfamily of transcription factors that can be
      activated by ligands and are involved in a wide range of physiological processes.
      NRs are well conserved between vertebrate species. The zebrafish, an increasingly
      popular animal model system, contains a total of 73 NR genes, and orthologues of
      almost all human NRs are present. In this review article, an overview is
      presented of NR research in which the zebrafish has been used as a model.
      Research is described on the three most studied zebrafish NRs: the estrogen
      receptors (ERs), retinoic acid receptors (RARs) and peroxisome proliferator
      activated receptors (PPARs). The studies on these receptors illustrate the
      versatility of the zebrafish as a model for ecotoxicological, developmental and
      biomedical research. Although the use of the zebrafish in NR research is still
      relatively limited, it is expected that in the next decade the full potential of
      this animal model will be exploited.

PMID- 28438787
TI  - Mortality from cancer and other causes among Italian chrysotile asbestos miners.
AB  - OBJECTIVE: To investigate the long-term mortality of a cohort of Italian asbestos
      miners. METHODS: The cohort included 1056 men employed in a chrysotile mine
      between 1930 and 1990, who were followed up during 1946-2014, for a total of 37
      471 person-years of observation. Expected deaths and SMRs were computed using
      national and local (after 1980, when available) reference. RESULTS: A total of
      294 (27.8%) subjects were alive and at the end of follow-up, 722 (68.4%) were
      dead and 40 (3.8%) were lost to follow-up. The SMR for overall mortality was 1.35
      (95%CI 1.25 to 1.45). The SMR for pleural cancer, based on seven observed deaths,
      was 5.54 (95% CI 2.22 to 11.4) and related to time since first exposure, but not
      to duration of employment, cumulative exposure or time since last exposure. The
      SMR for lung cancer was 1.16 (95% CI 0.87 to 1.52; 53 observed deaths), with no
      excess among workers with cumulative exposure below 100 fibre/mL-years (SMR 0.82;
      95% CI 0.44 to 1.40). CONCLUSIONS: The update of the follow-up of this cohort
      confirmed an increased mortality from pleural cancer mortality in miners exposed
      to chrysotile and a lack of significant increase in lung cancer mortality.

PMID- 28438786
TI  - VEGFR2 but not VEGFR3 governs integrity and remodeling of thyroid angiofollicular
      unit in normal state and during goitrogenesis.
AB  - Thyroid gland vasculature has a distinguishable characteristic of endothelial
      fenestrae, a critical component for proper molecular transport. However, the
      signaling pathway that critically governs the maintenance of thyroid vascular
      integrity, including endothelial fenestrae, is poorly understood. Here, we found
      profound and distinct expression of follicular epithelial VEGF-A and vascular
      VEGFR2 that were precisely regulated by circulating thyrotropin, while there were
      no meaningful expression of angiopoietin-Tie2 system in the thyroid gland. Our
      genetic depletion experiments revealed that VEGFR2, but not VEGFR3, is
      indispensable for maintenance of thyroid vascular integrity. Notably, blockade of
      VEGF-A or VEGFR2 not only abrogated vascular remodeling but also inhibited
      follicular hypertrophy, which led to the reduction of thyroid weights during
      goitrogenesis. Importantly, VEGFR2 blockade alone was sufficient to cause a
      reduction of endothelial fenestrae with decreases in thyrotropin-responsive genes
      in goitrogen-fed thyroids. Collectively, these findings establish follicular VEGF
      A-vascular VEGFR2 axis as a main regulator for thyrotropin-dependent thyroid
      angiofollicular remodeling and goitrogenesis.

PMID- 28438788
TI  - Associations between persistent organic pollutants, type 2 diabetes, diabetic
      nephropathy and mortality.
AB  - OBJECTIVE: Relationships were examined between persistent organic pollutants
      (POPs) and incident type 2 diabetes, end-stage renal disease (ESRD) and
      mortality. METHODS: In a nested case-control study, 300 persons without diabetes
      had baseline examinations between 1969 and 1974; 149 developed diabetes (cases)
      and 151 remained non-diabetic (controls) during 8.0 and 23.1 years of follow-up,
      respectively. POPs were measured at baseline. ORs for diabetes were computed by
      logistic regression analysis. The cases were followed from diabetes onset to
      ESRD, death or 2013. HRs for ESRD and mortality were computed by cause-specific
      hazard models. Patterns of association were explored using principal components
      analysis. RESULTS: PCB151 increased the odds for incident diabetes, whereas
      hexachlorobenzene (HCB) was protective after adjusting for age, sex, body mass
      index, sample storage characteristics, glucose and lipid levels. Associations
      between incident diabetes and polychlorinatedbiphenyl (PCB) or persistent
      pesticide (PST) components were mostly positive but non-significant. Among the
      cases, 29 developed ESRD and 48 died without ESRD. PCB28, PCB49 and PCB44
      increased the risk of ESRD after adjusting for baseline demographic and clinical
      characteristics. Several PCBs and PSTs increased the risk of death without ESRD.
      The principal components analysis identified PCBs with low-chlorine load
      positively associated with ESRD and death without ESRD, and several PSTs
      associated with death without ESRD. CONCLUSIONS: Most POPs were positively but
      not significantly associated with incident diabetes. PCB151 was significantly
      predictive and HCB was significantly protective for diabetes. Among participants
      with diabetes, low-chlorine PCBs increase the risk of ESRD and death without
      ESRD, whereas several PSTs predict death without ESRD.

PMID- 28438789
TI  - Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma
      keratinocytes.
AB  - Extracellular vesicles (EVs) are nanoscale membrane-derived vesicles that serve
      as intercellular messengers carrying lipids, proteins, and genetic material.
      Substantial evidence has shown that cancer-derived EVs, secreted by tumor cells
      into the blood and other bodily fluids, play a critical role in modulating the
      tumor microenvironment and affecting the pathogenesis of cancer. Here we
      demonstrate for the first time that squamous cell carcinoma (SCC) EVs were
      enriched with the C-terminal fragment of desmoglein 2 (Dsg2), a desmosomal
      cadherin often overexpressed in malignancies. Overexpression of Dsg2 increased EV
      release and mitogenic content including epidermal growth factor receptor and c
      Src. Inhibiting ectodomain shedding of Dsg2 with the matrix metalloproteinase
      inhibitor GM6001 resulted in accumulation of full-length Dsg2 in EVs and reduced
      EV release. When cocultured with Dsg2/green fluorescence protein-expressing SCC
      cells, green fluorescence protein signal was detected by fluorescence-activated
      cell sorting analysis in the CD90+ fibroblasts. Furthermore, SCC EVs activated
      Erk1/2 and Akt signaling and enhanced fibroblast cell proliferation. In vivo,
      Dsg2 was highly up-regulated in the head and neck SCCs, and EVs isolated from
      sera of patients with SCC were enriched in Dsg2 C-terminal fragment and epidermal
      growth factor receptor. This study defines a mechanism by which Dsg2 expression
      in cancer cells can modulate the tumor microenvironment, a step critical for
      tumor progression.-Overmiller, A. M., Pierluissi, J. A., Wermuth, P. J., Sauma,
      S., Martinez-Outschoorn, U., Tuluc, M., Luginbuhl, A., Curry, J., Harshyne, L.
      A., Wahl, J. K. III, South, A. P., Mahoney, M. G. Desmoglein 2 modulates
      extracellular vesicle release from squamous cell carcinoma keratinocytes.

PMID- 28438791
TI  - Margaret McCartney: Medical school interview courses are needless and unfair.

PMID- 28438790
TI  - Psychiatric associations of adult-onset focal dystonia phenotypes.
AB  - BACKGROUND: Depression and anxiety frequently accompany the motor manifestations
      of isolated adult-onset focal dystonias. Whether the body region affected when
      this type of dystonia first presents is associated with the severity of these
      neuropsychiatric symptoms is unknown. OBJECTIVES: The aim of this study was to
      determine whether depression, anxiety and social anxiety vary by dystonia onset
      site and evaluate whether pain and dystonia severity account for any differences.
      METHODS: Patients with isolated focal dystonia evaluated within 5 years from
      symptom onset, enrolled in the Natural History Project of the Dystonia Coalition,
      were included in the analysis. Individual onset sites were grouped into five body
      regions: cervical, laryngeal, limb, lower cranial and upper cranial.
      Neuropsychiatric symptoms were rated using the Beck Depression Inventory,
      Hospital Anxiety and Depression Scale and Liebowitz Social Anxiety Scale. Pain
      was estimated using the 36-Item Short Form Survey. RESULTS: Four hundred and
      seventy-eight subjects met our inclusion criteria. High levels of depression,
      anxiety and social anxiety occurred in all groups; however, the severity of
      anxiety and social anxiety symptoms varied by onset site group. The most
      pronounced differences were higher anxiety in cervical and laryngeal, lower
      anxiety in upper cranial and higher social anxiety in laryngeal. Increases in
      pain were associated with worse neuropsychiatric symptom scores within all
      groups. Higher anxiety and social anxiety in laryngeal and lower anxiety in upper
      cranial persisted after correcting for pain and dystonia severity. CONCLUSION:
      Anxiety and social anxiety severity vary by onset site of focal dystonia, and
      this variation is not explained by differences in pain and dystonia severity.

PMID- 28438792
TI  - Reconstitution of Abscisic Acid Signaling from the Receptor to DNA via bHLH
      Transcription Factors.
AB  - The plant hormone abscisic acid (ABA) confers drought tolerance in plants through
      stomatal closure and regulation of gene expression. The complex consisting of the
      ABA receptor PYRABACTIN RESISTANCE/REGULATORY COMPONENTS OF ABA RECEPTOR
      (PYR/RCAR), type 2C protein phosphatase (PP2C), and SNF1-related protein kinase 2
      (SnRK2) has a key role in ABA signaling. Basic helix-loop-helix (bHLH)
      transcriptional activator ABA-RESPONSIVE KINASE SUBSTRATE1 (AKS1, also known as
      FBH3) is released from DNA by phosphorylation-induced monomerization in response
      to ABA in guard cells. Here we reconstituted the release of AKS1 from DNA via the
      ABA signaling core complex in vitro. We first obtained evidence to confirm that
      AKS1 is an endogenous substrate for SnRK2s. Phosphorylation of AKS1 and
      activation of SnRK2 showed the same time course in response to ABA in guard
      cells. AKS1 was bound to SnRK2.6 in vivo. Three ABA-responsive SnRK2s
      (SnRK2.2/SRK2D, SnRK2.3/SRK2I, and SnRK2.6/SRK2E/OST1) phosphorylated AKS1 in
      vitro, and the phosphorylation was eliminated by the triple mutation of SnRK2s in
      plants. We reconstituted the AKS1 phosphorylation in vitro via the signaling
      complex containing the ABA receptor PYR1, a PP2C, HYPERSENSITIVE TO ABA1 (HAB1),
      and a protein kinase, SnRK2.6 in response to ABA We further reconstituted the
      release of AKS1 from the target gene of POTASSIUM CHANNEL IN ARABIDOPSIS THALIANA
      1 (KAT1) via the complex in response to ABA These results demonstrate that AKS1
      provides a link between the signaling complex and ABA-responsive genes and
      furnish evidence for a minimal signaling mechanism from ABA perception to DNA.

PMID- 28438794
TI  - Intraductal oncocytic papillary neoplasm: a benign hepatic cystic neoplasm.
AB  - A 61-year-old Asian man presented with severe right upper quadrant pain which had
      been worsening for several months. Laboratory results indicated elevated
      aspartate aminotransferase and alanine aminotransferase. The subsequent
      ultrasound, CT and MRI showed a large cystic mass with solid components and
      severe intrahepatic and extrahepatic biliary ductal dilatation. The mass was
      resected and pathology showed a well-demarcated mucinous cystic lesion with
      polygonal cells containing ovoid nuclei and abundant pink oncocytic cytoplasm.
      These findings are characteristic of intraductal oncocytic papillary neoplasm
      (IOPN), a rare subtype of intraductal papillary neoplasm of the liver. IOPN
      occurs most frequently in the Asian regions endemic to clonorchiasis and
      hepatolithiasis; however, cases have been reported in the Western world as well.
      Patients with IOPN are male or female and typically middle-aged. Treatment is
      typically resection. Prognosis is favourable and recurrence is rare. The 5-year
      survival rate is upwards of 80%.

PMID- 28438793
TI  - Brassinosteroid Biosynthesis Is Modulated via a Transcription Factor Cascade of
      COG1, PIF4, and PIF5.
AB  - Brassinosteroids (BRs) are essential phytohormones regulating various
      developmental and physiological processes during normal growth and development.
      cog1-3D (cogwheel1-3D) was identified as an activation-tagged genetic modifier of
      bri1-5, an intermediate BR receptor mutant in Arabidopsis (Arabidopsis thaliana).
      COG1 encodes a Dof-type transcription factor found previously to act as a
      negative regulator of the phytochrome signaling pathway. cog1-3D single mutants
      show an elongated hypocotyl phenotype under light conditions. A loss-of-function
      mutant or inducible expression of a dominant negative form of COG1 in the wild
      type results in an opposite phenotype. A BR profile assay indicated that BR
      levels are elevated in cog1-3D seedlings. Quantitative reverse transcription
      polymerase chain reaction analyses showed that several key BR biosynthetic genes
      are significantly up-regulated in cog1-3D compared with those of the wild type.
      Two basic helix-loop-helix transcription factors, PIF4 and PIF5, were found to be
      transcriptionally up-regulated in cog1-3D Genetic analysis indicated that PIF4
      and PIF5 were required for COG1 to promote BR biosynthesis and hypocotyl
      elongation. Chromatin immunoprecipitation and electrophoretic mobility shift
      assays indicated that COG1 binds to the promoter regions of PIF4 and PIF5, and
      PIF4 and PIF5 bind to the promoter regions of key BR biosynthetic genes, such as
      DWF4 and BR6ox2, to directly promote their expression. These results demonstrated
      that COG1 regulates BR biosynthesis via up-regulating the transcription of PIF4
      and PIF5.

PMID- 28438795
TI  - Cystic tumour of the atrioventricular node: treatment dilemma.
AB  - An asymptomatic 18-year-old black woman was found to have an incidental finding
      of third-degree atrioventricular (AV) block on a routine ECG. 2-Dimensional
      transthoracic echocardiography showed a heterogeneous mass in the region of the
      peri-membranous septum in the AV node area. A cardiac MRI showed a well-defined
      cystic mass arising from the right side of the interatrial septal wall. An MRI
      compatible permanent pacemaker was implanted with plans to monitor the tumour
      with non-invasive imaging. Cystic tumour of the AV node is a rare primary cardiac
      tumour. It is known as the smallest and most common primary cardiac tumour that
      can cause sudden death. All previous six cases of living patients with cystic
      tumour of the AV node reported in the literature were females and symptomatic. We
      present a rare case of a patient with cystic tumour of the AV node, and we
      highlight the treatment dilemmas for this condition.

PMID- 28438796
TI  - Critical Need for Clarity in Polymyxin B Dosing.

PMID- 28438797
TI  - Importance of Sequencing To Determine Functional blaTEM Variants.

PMID- 28438798
TI  - Reply to Furlan et al., "Importance of Sequencing To Determine Functional blaTEM
      Variants".

PMID- 28438799
TI  - Erratum for Gonzalez-Herrera et al., "Simvastatin Attenuates Endothelial
      Activation through 15-Epi-Lipoxin A4 Production in Murine Chronic Chagas
      Cardiomyopathy".

PMID- 28438800
TI  - On the brink of conflict: the people of South Asia deserve better.

PMID- 28438801
TI  - Complete Immediate Revascularization of the Patient With ST-Segment-Elevation
      Myocardial Infarction Is the New Standard of Care.

PMID- 28438802
TI  - Not So Fast: Complete Revascularization of the ST-Segment-Elevation Myocardial
      Infarction Patient Is Not Yet Proven.

PMID- 28438803
TI  - Clinician's Guide to Early Rule-Out Strategies With High-Sensitivity Cardiac
      Troponin.

PMID- 28438804
TI  - Hypertension Treatment and Outcomes in the Era of Population Health, Coordinated
      Care, and Medicare Access and CHIP Reauthorization Act (MACRA).

PMID- 28438805
TI  - Subcellular Remodeling of the T-Tubule Membrane System: The Limits of Myocardial
      Recovery Revealed?

PMID- 28438807
TI  - Highlights From the Circulation Family of Journals.

PMID- 28438808
TI  - Gut Microbe-Generated Trimethylamine N-Oxide From Dietary Choline Is
      Prothrombotic in Subjects.

PMID- 28438806
TI  - Emerging Affinity-Based Proteomic Technologies for Large-Scale Plasma Profiling
      in Cardiovascular Disease.
AB  - Plasma biomarkers that reflect molecular states of the cardiovascular system are
      central for clinical decision making. Routinely used plasma biomarkers include
      troponins, natriuretic peptides, and lipoprotein particles, yet interrogate only
      a modest subset of pathways relevant to cardiovascular disease. Systematic
      profiling of a larger portion of circulating plasma proteins (the plasma
      proteome) will provide opportunities for unbiased discovery of novel markers to
      improve diagnostic or predictive accuracy. In addition, proteomic profiling may
      inform pathophysiological understanding and point to novel therapeutic targets.
      Obstacles for comprehensive proteomic profiling include the immense size and
      structural heterogeneity of the proteome, and the broad range of abundance
      levels, as well. Proteome-wide, untargeted profiling can be performed in tissues
      and cells with tandem mass spectrometry. However, applications to plasma are
      limited by the need for complex preanalytical sample preparation stages limiting
      sample throughput. Multiplexing of targeted methods based on capture and
      detection of specific proteins are therefore receiving increasing attention in
      plasma proteomics. Immunoaffinity assays are the workhorse for measuring
      individual proteins but have been limited for proteomic applications by long
      development times, cross-reactivity preventing multiplexing, specificity issues,
      and incomplete sensitivity to detect proteins in the lower range of the abundance
      spectrum (below picograms per milliliter). Emerging technologies to address these
      issues include nucleotide-labeled immunoassays and aptamer reagents that can be
      automated for efficient multiplexing of thousands of proteins at high sample
      throughput, coupling of affinity capture methods to mass spectrometry for
      improved specificity, and ultrasensitive detection systems to measure low
      abundance proteins. In addition, proteomics can now be integrated with modern
      genomics tools to comprehensively relate proteomic profiles to genetic variants,
      which may both influence binding of affinity reagents and serve to validate the
      target specificity of affinity assays. The application of deep quantitative
      proteomic profiling to large cohorts has thus become increasingly feasible with
      emerging affinity methods. The aims of this article are to provide the broad
      readership of Circulation with a timely overview of emerging methods for affinity
      proteomics and recent progress in cardiovascular medicine based on such methods.

PMID- 28438809
TI  - Letter by Downey and Cohen Regarding Article, "Protective Effects of Ticagrelor
      on Myocardial Injury After Infarction".

PMID- 28438810
TI  - Letter by Fernandez-Jimenez et al Regarding Article, "Protective Effects of
      Ticagrelor on Myocardial Injury After Infarction".

PMID- 28438811
TI  - Response by Vilahur et al to Letters Regarding Article, "Protective Effects of
      Ticagrelor on Myocardial Injury After Infarction".

PMID- 28438812
TI  - Letter by Koh Regarding Article, "Pleiotropic Effects of PCSK9 (Proprotein
      Convertase Subtilisin/Kexin Type 9) Inhibitors?"

PMID- 28438814
TI  - New drugs and dosage forms.

PMID- 28438813
TI  - Evaluation of medication management programs proves difficult.

PMID- 28438815
TI  - Wyoming pharmacists help homeless manage their medications.

PMID- 28438817
TI  - Pharmacists help patients get started on hepatitis C regimens.

PMID- 28438819
TI  - Essentials of essential oils.
AB  - PURPOSE: Information to guide clinicians in educating and advising patients using
      or intending to use essential oils for self-administered aromatherapy or other
      medicinal purposes is presented. SUMMARY: The term essential oils refers to
      highly concentrated, aromatic oils extracted from plants by steam distillation,
      hydrodiffusion, or pressure. Market reports indicate strong growth in the use of
      essential oils in the United States in recent decades. Therapeutic claims made in
      the marketing of essential oils have led the Food and Drug Administration to
      caution a number of suppliers. Along with rapid growth in sales of essential oils
      to consumers there has been an increase in the amount of published evidence
      regarding aromatherapy and essential oils; the annual number of relevant articles
      indexed using Medical Subject Headings terminology has doubled since 2004. In
      order to help ensure proper application and safe use of essential oils as a self
      care modality, healthcare professionals can benefit from a general knowledge of
      the terminology and foundational concepts of medicinal use of essential oils, as
      well as resources to facilitate evaluations of appropriateness of use.
      CONCLUSION: Because of the increasing popularity of essential oils and the
      prevalence of essential oil-based self-care practices targeting a wide variety of
      ailments in the United States, healthcare professionals must be prepared to
      address concerns about the agents' safety and efficacy. Proper literature
      evaluation requires the ability to discern the quality of an oil, the safety of
      administration, and the validity of its use.

PMID- 28438820
TI  - Use of an argatroban-based purge solution in a percutaneous ventricular assist
      device.
AB  - PURPOSE: The use of an argatroban-based percutaneous ventricular assist device
      (pVAD) purge solution in a patient with suspected heparin-induced
      thrombocytopenia (HIT) is described. SUMMARY: A 70-year-old woman in cardiogenic
      shock was admitted to a coronary care unit after being discovered unresponsive at
      home. A transthoracic echocardiogram revealed a low ejection fraction and
      findings consistent with takotsubo cardiomyopathy. Administration of multiple
      inotropes and vasopressors was initially required for hemodynamic support. The
      patient was implanted with an Impella pVAD (Abiomed, Inc., Danvers, MA) using a
      heparin-based purge solution; an i.v. heparin infusion was initiated for
      supplemental systemic anticoagulation. Over the next 24 hours, the patient's
      platelet count decreased from 168,000 to 37,000 cells/MUL. Given a differential
      diagnosis that included HIT, the patient was transitioned to an argatroban-based
      purge solution. Due to prolonged activated partial thromboplastin times, a
      systemic argatroban infusion was not initiated, and the patient remained fully
      anticoagulated throughout pVAD support with only the argatroban-based purge
      solution. An HIT antibody test was negative. On hospitalization day 9 (day 6 of
      pVAD support with argatroban use), the patient became hemodynamically stable and
      was weaned off pVAD support. Three days later, the platelet count had recovered
      to 117,000 cells/MUL (from a nadir of 21,000 cells/MUL). During pVAD support, the
      patient developed hemolytic anemia with minimal bleeding complications.
      CONCLUSION: Argatroban was used as a purge solution anticoagulant in a patient
      with an Impella pVAD and found to be a safe and effective alternative to heparin.

PMID- 28438821
TI  - Effects of i.v. push administration on beta-lactam pharmacodynamics.
AB  - PURPOSE: The effects of i.v. push administration on the pharmacodynamic exposures
      of meropenem, cefepime, and aztreonam were evaluated. METHODS: Pharmacokinetic
      and pharmacodynamic analyses were conducted using previously published
      pharmacokinetic data for meropenem, cefepime, and aztreonam. The probability of
      target attainment (PTA) was assessed using Monte Carlo simulations for 30-minute
      and 5-minute infusions of approved dosing regimens and alternative dosing schemes
      often used in clinical practice, including 500 mg every 6 hours and 1 g every 8
      hours for meropenem, 1 g every 6 hours and 2 g every 8 hours for cefepime, and 2
      g every 8 hours for aztreonam. For each regimen examined, means and standard
      deviations for the percentage of the dosing interval that the free drug
      concentration remained above the minimum inhibitory concentration (MIC) were
      calculated and reported. RESULTS: No or only minor differences were noted between
      30-minute and 5-minute infusions. The largest differences were observed at an MIC
      of 4 mg/L for meropenem and an MIC of 16 mg/L for aztreonam. At an MIC of 4 mg/L,
      meropenem 500 mg every 6 hours as a 30-minute infusion had an 8% greater PTA
      compared with the 5-minute infusion. At an MIC of 16 mg/L, a 30-minute infusion
      of aztreonam 2 g every 8 hours had a 12% greater PTA compared with the 5-minute
      infusion. CONCLUSION: Simulations of meropenem, cefepime, and aztreonam by i.v.
      push over 5 minutes indicated that there would be minimal or no effect on
      pharmacodynamic exposures compared with the effect when administered by 30-minute
      infusions.

PMID- 28438822
TI  - Efficacy and safety of topical sevoflurane in the treatment of chronic skin
      ulcers.
AB  - PURPOSE: Results of efficacy and safety assessments of topical sevoflurane use in
      patients with long-term treatment-refractory vascular ulcers are reported.
      METHODS: Patients were randomly assigned to receive sevoflurane instillations (1
      mL per cm2 of ulcer area 1-4 times daily) plus standard wound care (ulcer
      cleaning, debridement, and dressing changes) or standard care only. Topical
      sevoflurane was initiated during hospitalization, with self- or nurse
      administered instillations continued after discharge. Study participants were
      evaluated at least once weekly for 1 month and then every 2 weeks for up to 90
      days. The primary efficacy measures were debridement-related and overall pain
      (assessed using a 10-point visual analog scale), daily opioid use, and ulcer
      size; secondary measures were patient and clinician impressions of improvement
      and ulcer-related admissions during treatment. The primary safety endpoint was
      intolerable sevoflurane-related adverse effects. RESULTS: Compared with the group
      receiving standard care alone (n = 5), the sevoflurane group (n = 10) had
      significant (p = 0.001) reductions in mean +/- S.D. scores for debridement
      related pain on day 1 of treatment and at subsequent time points; the sevoflurane
      group also had significant reductions in overall pain, daily opioid use, and
      ulcer size. Outcomes in terms of patient- and clinician-rated improvement and
      emergency admissions also favored the sevoflurane group. Mild localized reddening
      in the area surrounding ulcers occurred in 4 sevoflurane-treated patients.
      CONCLUSION: Direct application of sevoflurane onto vascular ulcers resulted in an
      intense and long-lasting analgesia and was associated with a progressive
      reduction of ulcer size.

PMID- 28438823
TI  - Association of human leukocyte antigen variants and allopurinol-induced Stevens
      Johnson syndrome and toxic epidermal necrolysis: A meta-analysis.
AB  - PURPOSE: The association between human leukocyte antigen (HLA) variants and
      allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
      (TEN) was evaluated through a pooled analysis of published studies. METHODS: A
      comprehensive search was performed in multiple databases, including PubMed,
      MEDLINE, ISI Web of Knowledge, EMBASE, Cochrane Register of Controlled Trials,
      and Science Direct. Studies investigating the association between HLA alleles
      with allopurinol-induced SJS or TEN were retrieved, and the data were
      independently extracted. The overall odds ratios (ORs) with corresponding 95%
      confidence intervals were calculated to determine the association between the
      presence of HLA variant in at least one allele and allopurinol-induced SJS or
      TEN. To test the robustness of the meta-analysis results, a sensitivity analysis
      was performed by removing each study one at a time and calculating the pooled ORs
      of the remaining studies. The fixed-effects and random-effects models were used
      to pool the collected data. RESULTS: A total of 4 studies with 81 allopurinol
      induced SJS or TEN cases and matched controls (allopurinol-tolerant patients) or
      population controls (general population) were identified. SJS and TEN were found
      to be significantly associated with HLA-A*33:03 and HLA-C*03:02 alleles in both
      groups of studies with matched controls and population controls. All of the
      pooled ORs were not significantly affected by the remaining studies and different
      modeling methods, indicating robust results. CONCLUSION: A strong association was
      found between HLA-A*33:03 and HLA-C*03:02 alleles and allopurinol-induced SJS or
      TEN, especially in an Asian population.

PMID- 28438824
TI  - Comparison of linezolid and vancomycin lock solutions with and without heparin
      against biofilm-producing bacteria.
AB  - PURPOSE: The activity of linezolid and vancomycin lock solutions against biofilm
      producing strains of Staphylococcus aureus, S. epidermidis, and Enterococcus
      faecalis was studied. METHODS: Two strains each of methicillin-susceptible S.
      aureus (MSSA), methicillin-resistant S. aureus (MRSA), and S. epidermidis, and 1
      strain of vancomycin-susceptible E. faecalis and vancomycin-resistant E. faecalis
      were tested against vancomycin and linezolid to assess prevention of biofilm
      formation and eradication of these pathogens within a formed biofilm. Activity
      was also tested in a 72-hour in vitro central venous catheter (CVC) model. After
      24 hours of biofilm growth in a CVC, a lock solution containing vancomycin (2 or
      5 mg/mL) or linezolid (1 or 2 mg/mL) alone or in combination with heparin sodium
      (5,000 units/mL with benzyl alcohol 0.45%) was instilled and incubated at 35 
      degrees C for 72 hr. Heparin and 0.9% sodium chloride injection were also tested.
      RESULTS: Linezolid and vancomycin prevented biofilm formation below the minimum
      inhibitory concentration for 88% and 25% of isolates tested, respectively. The
      addition of preservative-containing heparin decreased the activity of vancomycin
      and linezolid lock solutions against all strains. Vancomycin 2- and 5-mg/mL lock
      solutions had the most activity against MSSA and E. faecalis strains (p < 0.01).
      Linezolid 2 mg/mL was the most active lock solution against the MRSA strains
      tested (p < 0.01). There were no significant differences in vancomycin or
      linezolid lock solution activity against S. epidermidis. CONCLUSION: Heparin
      reduced activity of vancomycin and linezolid lock solutions against S. aureus, S.
      epidermidis, and E. faecalis biofilms. While linezolid or vancomycin lock
      solution reduced overall biofilm burden, it did not completely eradicate the
      bacteria at tested concentrations.

PMID- 28438825
TI  - Beyond-use dating of lidocaine alone and in two "magic mouthwash" preparations.
AB  - PURPOSE: Beyond-use dating (BUD) of lidocaine alone and in two "magic mouthwash"
      preparations stored in amber oral syringes at room temperature was determined.
      METHODS: Two formulations of mouthwash containing oral topical lidocaine 2%
      (viscous), diphenhydramine 2.5 mg/mL, and aluminum hydroxide-magnesium hydroxide
      simethicone were prepared in 1:1:1 and 1:2.5:2.5 ratios, divided into 3-mL
      samples, and stored in unit-dose oral amber syringes. Unit-dose single-product
      lidocaine samples were also prepared to serve as controls and stored in oral
      amber syringes. The lidocaine concentrations in these samples were measured
      periodically for 90 days. A stability-indicating high-performance liquid
      chromatographic method was developed and validated for system suitability,
      accuracy, repeatability, intermediate precision, specificity, linearity, and
      robustness. RESULTS: Based on the calculated percentages versus the initial
      concentration and the results from an analysis of variance comparing the two
      formulations, a BUD of 21 days is deemed appropriate for both magic mouthwash
      formulations. Based on the stability data, published safety concerns, and lack of
      efficacy in combination, packaging and dispensing lidocaine separately from other
      ingredients are recommended when administering magic mouthwash mixtures.
      Utilizing a 90-day BUD, lidocaine can be packaged separately from other magic
      mouthwash ingredients in individual dosage units and applied to the oral cavity
      using the swish-and-spit method. The delivery of the diphenhydramine and aluminum
      hydroxide-magnesium hydroxide-simethicone could be separated, allowing for a
      swish-and-swallow method of administration. CONCLUSION: A BUD of 21 days is
      recommended for lidocaine prepared with diphenhydramine and aluminum hydroxide
      magnesium hydroxide-simethicone in ratios of 1:1:1 and 1:2.5:2.5 and stored at
      room temperature in amber oral plastic syringes.

PMID- 28438826
TI  - Stability study of methotrexate in 0.9% sodium chloride injection and 5% dextrose
      injection with limit tests for impurities.
AB  - PURPOSE: Results of an evaluation of the stability of methotrexate in 0.9% sodium
      chloride injection and 5% dextrose injection are presented. METHODS: Methotrexate
      concentrated solution (100 mg/mL) was diluted to nominal concentrations of 0.2
      and 20 mg/mL in infusion bags containing 0.9% sodium chloride injection or 5%
      dextrose injection. The filled bags were stored for 28 days at 25  degrees C and
      60% relative humidity and protected from light. Samples were withdrawn for
      analysis on the day of preparation and after 3, 7, 14, 21, and 28 days. The test
      program included visual inspections, measurements of pH and infusion bag weight
      loss, and high-performance liquid chromatography assays to determine methotrexate
      content and characterize degradation products. RESULTS: At both evaluated
      concentrations, methotrexate in 0.9% sodium chloride injection was stable for 28
      days; only minor (<0.05%) increases in amounts of known and unknown degradation
      products were detected. In 5% dextrose injection, methotrexate at the higher
      concentration was stable for 28 days, with minor formation of degradation
      products; in the 0.2-mg/mL solution, however, methotrexate was stable for only 3
      days. At later time points, an unknown impurity present at a concentration higher
      than 0.1% was observed. CONCLUSION: At concentrations of 0.2 and 20 mg/mL,
      methotrexate in 0.9% sodium chloride injection was found to be stable for 28 days
      when stored at 25  degrees C and protected from light. Under the same storage
      conditions, methotrexate in a 20-mg/mL solution prepared with 5% dextrose
      injection was stable for 28 days, whereas a 0.2-mg/mL solution in the same
      diluent was stable for only 3 days.

PMID- 28438827
TI  - Implementing a pharmacist consultation model for multimodal insulin therapy.
AB  - PURPOSE: The implementation of pharmacist-managed insulin dosing for selected
      hospitalized patients under a multimodal insulin protocol (MMIP) is described.
      SUMMARY: Hyperglycemia has been linked to increased thrombosis, decreased wound
      healing, and decreased immune response. Current recommendations support the use
      of multimodal (basal-bolus) insulin therapy in noncritically ill inpatients. As
      part of a systemwide quality-improvement initiative to improve glycemic
      management, the pharmacy department of a community hospital initiated a service
      to provide protocol-directed insulin dosing for selected patients under a
      pharmacist consultation model. An MMIP targeting patients with 2 blood glucose
      (BG) readings of >180 mg/dL within a 12-hour period was developed and approved.
      Pharmacist consultations, including patient assessment, entry of initial insulin
      orders, and ongoing insulin dosage adjustments, are performed pursuant to
      electronic notifications and computerized prescriber order entry. Noncritically
      ill patients who meet the criteria for protocol-guided insulin dosing are managed
      according to an approved weight-based MMIP for calculating and adjusting
      nutritional and basal insulin doses. Prior to the initiation of MMIP-guided
      insulin dosing, pharmacists were trained on the use of the protocol and passed a
      competency assessment. In the 90-day period after protocol implementation, 158
      hyperglycemic patients received pharmacist-managed insulin dosing. CONCLUSION:
      The goal of achieving a mean BG concentration of <=180 mg/dL by day 3 of
      hyperglycemia management under a pharmacist-managed MMIP was attained in the
      second and third months after protocol implementation.

PMID- 28438828
TI  - An assessment of currently available i.v. push medication delivery systems.

PMID- 28438829
TI  - ASHP Statement on Telepharmacy.

PMID- 28438830
TI  - Implementing shared decision making in the NHS: lessons from the MAGIC programme.

PMID- 28438831
TI  - Pathology and radiology taking medical 'hermeneutics' to the next level?

PMID- 28438832
TI  - A photoconversion model for full spectral programming and multiplexing of
      optogenetic systems.
AB  - Optogenetics combines externally applied light signals and genetically engineered
      photoreceptors to control cellular processes with unmatched precision. Here, we
      develop a mathematical model of wavelength- and intensity-dependent
      photoconversion, signaling, and output gene expression for our two previously
      engineered light-sensing Escherichia coli two-component systems. To parameterize
      the model, we develop a simple set of spectral and dynamical calibration
      experiments using our recent open-source "Light Plate Apparatus" device. In
      principle, the parameterized model should predict the gene expression response to
      any time-varying signal from any mixture of light sources with known spectra. We
      validate this capability experimentally using a suite of challenging light
      sources and signals very different from those used during the parameterization
      process. Furthermore, we use the model to compensate for significant spectral
      cross-reactivity inherent to the two sensors in order to develop a new method for
      programming two simultaneous and independent gene expression signals within the
      same cell. Our optogenetic multiplexing method will enable powerful new
      interrogations of how metabolic, signaling, and decision-making pathways
      integrate multiple input signals.

PMID- 28438833
TI  - The G protein Gi1 exhibits basal coupling but not preassembly with G protein
      coupled receptors.
AB  - The Gi/o protein family transduces signals from a diverse group of G protein
      coupled receptors (GPCRs). The observed specificity of Gi/o-GPCR coupling and the
      high rate of Gi/o signal transduction have been hypothesized to be enabled by the
      existence of stable associates between Gi/o proteins and their cognate GPCRs in
      the inactive state (Gi/o-GPCR preassembly). To test this hypothesis, we applied
      the recently developed technique of two-photon polarization microscopy (2PPM) to
      Galphai1 subunits labeled with fluorescent proteins and four GPCRs: the alpha2A
      adrenergic receptor, GABAB, cannabinoid receptor type 1 (CB1R), and dopamine
      receptor type 2. Our experiments with non-dissociating mutants of fluorescently
      labeled Galphai1 subunits (exhibiting impaired dissociation from activated GPCRs)
      showed that 2PPM is capable of detecting GPCR-G protein interactions. 2PPM
      experiments with non-mutated fluorescently labeled Galphai1 subunits and alpha2A
      adrenergic receptor, GABAB, or dopamine receptor type 2 receptors did not reveal
      any interaction between the Gi1 protein and the non-stimulated GPCRs. In
      contrast, non-stimulated CB1R exhibited an interaction with the Gi1 protein.
      Further experiments revealed that this interaction is caused solely by CB1R basal
      activity; no preassembly between CB1R and the Gi1 protein could be observed. Our
      results demonstrate that four diverse GPCRs do not preassemble with non-active
      Gi1 However, we also show that basal GPCR activity allows interactions between
      non-stimulated GPCRs and Gi1 (basal coupling). These findings suggest that Gi1
      interacts only with active GPCRs and that the well known high speed of GPCR
      signal transduction does not require preassembly between G proteins and GPCRs.

PMID- 28438834
TI  - RANKL cytokine enhances TNF-induced osteoclastogenesis independently of TNF
      receptor associated factor (TRAF) 6 by degrading TRAF3 in osteoclast precursors.
AB  - Cytokines, including receptor activator of nuclear factor kappaB ligand (RANKL)
      and TNF, induce increased osteoclast (OC) formation and bone loss in
      postmenopausal osteoporosis and inflammatory arthritides. RANKL and TNF can
      independently induce OC formation in vitro from WT OC precursors via TNF receptor
      associated factor (TRAF) adaptor proteins, which bind to their receptors. Of
      these, only TRAF6 is required for RANKL-induced osteoclastogenesis in vitro
      However, the molecular mechanisms involved remain incompletely understood. Here
      we report that RANKL induced the formation of bone-resorbing OCs from TRAF6-/- OC
      precursors when cultured on bone slices but not on plastic. The mechanisms
      involved increased TNF production by TRAF6-/- OC precursors resulting from their
      interaction with bone matrix and release of active TGFbeta from the resorbed
      bone, coupled with RANKL-induced autophagolysosomal degradation of TRAF3, a known
      inhibitor of OC formation. Consistent with these findings, RANKL enhanced TNF
      induced OC formation from TRAF6-/- OC precursors. Moreover, TNF induced
      significantly more OCs from mice with TRAF3 conditionally deleted in myeloid
      lineage cells, and it did not inhibit RANKL-induced OC formation from these
      cells. TRAF6-/- OC precursors that overexpressed TRAF3 or were treated with the
      autophagolysosome inhibitor chloroquine formed significantly fewer OCs in
      response to TNF alone or in combination with RANKL. We conclude that RANKL can
      enhance TNF-induced OC formation independently of TRAF6 by degrading TRAF3. These
      findings suggest that preventing TRAF3 degradation with drugs like chloroquine
      could reduce excessive OC formation in diseases in which bone resorption is
      increased in response to elevated production of these cytokines.

PMID- 28438835
TI  - Interleukin-1beta (IL-1beta) transcriptionally activates hepcidin by inducing
      CCAAT enhancer-binding protein delta (C/EBPdelta) expression in hepatocytes.
AB  - Hepcidin is a liver-derived hormone that negatively regulates serum iron levels
      and is mainly regulated at the transcriptional level. Previous studies have
      clarified that in addition to hepatic iron levels, inflammation also efficiently
      increases hepatic hepcidin expression. The principle regions responsible for
      efficient hepcidin transcription are bone morphogenetic protein-responsive
      elements (BMP-REs) 1 and 2 as well as the signal transducer and activator of
      transcription 3-binding site (STAT-BS). Here, we show that the proinflammatory
      cytokine interleukin-1beta (IL-1beta) efficiently increases hepcidin expression
      in human HepG2 liver-derived cells and primary mouse hepatocytes. The primary
      region responsible for IL-1beta-mediated hepcidin transcription was the putative
      CCAAT enhancer-binding protein (C/EBP)-binding site (C/EBP-BS) at the hepcidin
      promoter spanning nucleotides -329 to -320. IL-1beta induces the expression of
      C/EBPdelta but neither C/EBPalpha nor C/EBPbeta in hepatocytes, and C/EBPdelta
      bound to the C/EBP-BS in an IL-1beta-dependent manner. Lipopolysaccharide (LPS)
      induced the expression of IL-1beta in Kupffer cells and hepatocytes in the mouse
      liver; furthermore, the culture supernatants from the macrophage-like cell line
      RAW264.7 treated with LPS potentiated the stimulation of hepcidin expression in
      hepatocytes. The present study reveals that: 1) inflammation induces IL-1beta
      production in Kupffer cells and hepatocytes; 2) IL-1beta increases C/EBPdelta
      expression in hepatocytes; and 3) induction of C/EBPdelta activates hepcidin
      transcription via the C/EBP-BS that has been uncharacterized yet. In cooperation
      with the other pathways activated by inflammation, IL-1beta pathway stimulation
      leads to excess production of hepcidin, which could be causative to anemia of
      inflammation.

PMID- 28438836
TI  - A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue
      development.
AB  - The tongue is one of the major structures involved in human food intake and
      speech. Tongue malformations such as aglossia, microglossia, and ankyloglossia
      are congenital birth defects, greatly affecting individuals' quality of life.
      However, the molecular basis of the tissue-tissue interactions that ensure tissue
      morphogenesis to form a functional tongue remains largely unknown. Here we show
      that ShhCre -mediated epithelial deletion of Wntless (Wls), the key regulator for
      intracellular Wnt trafficking, leads to lingual hypoplasia in mice. Disruption of
      epithelial Wnt production by Wls deletion in epithelial cells led to a failure in
      lingual epidermal stratification and loss of the lamina propria and the
      underlying superior longitudinal muscle in developing mouse tongues. These
      defective phenotypes resulted from a reduction in epithelial basal cells positive
      for the basal epidermal marker protein p63 and from impaired proliferation and
      differentiation in connective tissue and paired box 3 (Pax3)- and Pax7-positive
      muscle progenitor cells. We also found that epithelial Wnt production is required
      for activation of the Notch signaling pathway, which promotes proliferation of
      myogenic progenitor cells. Notch signaling in turn negatively regulated Wnt
      signaling during tongue morphogenesis. We further show that Pax7 is a direct
      Notch target gene in the embryonic tongue. In summary, our findings demonstrate a
      key role for the lingual epithelial signals in supporting the integrity of the
      lamina propria and muscular tissue during tongue development and that a
      Wnt/Notch/Pax7 genetic hierarchy is involved in this development.

PMID- 28438837
TI  - An unpredicted aggregation-critical region of the actin-polymerizing protein
      TRIOBP-1/Tara, determined by elucidation of its domain structure.
AB  - Aggregation of specific proteins in the brains of patients with chronic mental
      illness as a result of disruptions in proteostasis is an emerging theme in the
      study of schizophrenia in particular. Proteins including DISC1 (disrupted in
      schizophrenia 1) and dysbindin-1B are found in insoluble forms within brain
      homogenates from such patients. We recently identified TRIOBP-1 (Trio-binding
      protein 1, also known as Tara) to be another such protein through an epitope
      discovery and proteomics approach by comparing post-mortem brain material from
      schizophrenia patients and control individuals. We hypothesized that this was
      likely to occur as a result of a specific subcellular process and that it,
      therefore, should be possible to identify a region of the TRIOBP-1 protein that
      is essential for its aggregation to occur. Here, we probe the domain organization
      of TRIOBP-1, finding it to possess two distinct coiled-coil domains: the central
      and C-terminal domains. The central domain inhibits the depolymerization of F
      actin and is also responsible for oligomerization of TRIOBP-1. Along with an N
      terminal pleckstrin homology domain, the central domain affects neurite
      outgrowth. In neuroblastoma cells it was found that the aggregation propensity of
      TRIOBP-1 arises from its central domain, with a short "linker" region narrowed to
      within amino acids 324-348, between its first two coiled coils, as essential for
      the formation of TRIOBP-1 aggregates. TRIOBP-1 aggregation, therefore, appears to
      occur through one or more specific cellular mechanisms, which therefore have the
      potential to be of physiological relevance for the biological process underlying
      the development of chronic mental illness.

PMID- 28438839
TI  - Spotlight on the April 25 issue.

PMID- 28438840
TI  - Gaining perspective on SUDEP: The new guideline.

PMID- 28438841
TI  - Practice guideline summary: Sudden unexpected death in epilepsy incidence rates
      and risk factors: Report of the Guideline Development, Dissemination, and
      Implementation Subcommittee of the American Academy of Neurology and the American
      Epilepsy Society.
AB  - OBJECTIVE: To determine the incidence rates of sudden unexpected death in
      epilepsy (SUDEP) in different epilepsy populations and address the question of
      whether risk factors for SUDEP have been identified. METHODS: Systematic review
      of evidence; modified Grading Recommendations Assessment, Development, and
      Evaluation process for developing conclusions; recommendations developed by
      consensus. RESULTS: Findings for incidence rates based on 12 Class I studies
      include the following: SUDEP risk in children with epilepsy (aged 0-17 years) is
      0.22/1,000 patient-years (95% confidence interval [CI] 0.16-0.31) (moderate
      confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient
      years (95% CI 0.64-2.32) (low confidence in evidence). The major risk factor for
      SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP
      risk increases in association with increasing frequency of GTCS occurrence (high
      confidence in evidence). RECOMMENDATIONS: Level B: Clinicians caring for young
      children with epilepsy should inform parents/guardians that in 1 year, SUDEP
      typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will
      not be affected. Clinicians should inform adult patients with epilepsy that SUDEP
      typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually
      999 of 1,000 adults will not be affected. For persons with epilepsy who continue
      to experience GTCS, clinicians should continue to actively manage epilepsy
      therapies to reduce seizures and SUDEP risk while incorporating patient
      preferences and weighing the risks and benefits of any new approach. Clinicians
      should inform persons with epilepsy that seizure freedom, particularly freedom
      from GTCS, is strongly associated with decreased SUDEP risk.

PMID- 28438838
TI  - Allosteric mechanism of action of the therapeutic anti-IgE antibody omalizumab.
AB  - Immunoglobulin E and its interactions with receptors FcepsilonRI and CD23 play a
      central role in allergic disease. Omalizumab, a clinically approved therapeutic
      antibody, inhibits the interaction between IgE and FcepsilonRI, preventing mast
      cell and basophil activation, and blocks IgE binding to CD23 on B cells and
      antigen-presenting cells. We solved the crystal structure of the complex between
      an omalizumab-derived Fab and IgE-Fc, with one Fab bound to each Cepsilon3
      domain. Free IgE-Fc adopts an acutely bent structure, but in the complex it is
      only partially bent, with large-scale conformational changes in the Cepsilon3
      domains that inhibit the interaction with FcepsilonRI. CD23 binding is inhibited
      sterically due to overlapping binding sites on each Cepsilon3 domain. Studies of
      omalizumab Fab binding in solution demonstrate the allosteric basis for
      FcepsilonRI inhibition and, together with the structure, reveal how omalizumab
      may accelerate dissociation of receptor-bound IgE from FcepsilonRI, exploiting
      the intrinsic flexibility and allosteric potential of IgE.

PMID- 28438842
TI  - Editors' Note.

PMID- 28438843
TI  - Letter re: Hand postures in primary and secondary generalized tonic-clonic
      seizures.

PMID- 28438845
TI  - Letter re: Long-term improvement in obsessions and compulsions with subthalamic
      stimulation.

PMID- 28438844
TI  - Author response: Hand postures in primary and secondary generalized tonic-clonic
      seizures.

PMID- 28438846
TI  - Author response: Long-term improvement in obsessions and compulsions with
      subthalamic stimulation.

PMID- 28438847
TI  - The common stroke.

PMID- 28438848
TI  - Clinical Reasoning: A 71-year-old woman with subacute progressive distal weakness
      and paresthesia after vaccination.

PMID- 28438849
TI  - Pearls & Oy-sters: Low-pressure hydrocephalus and inadequate shunting.

PMID- 28438850
TI  - Teaching NeuroImages: Acute infarction of the left medial lemniscus masquerading
      as a peripheral neuropathy.

PMID- 28438851
TI  - Predicting growth of brain aneurysms.

PMID- 28438853
TI  - Factors Associated with Microalbuminuria Remission in Patients with Type 2
      Diabetes: Importance of Early Intervention for Microalbuminuric Patients (TSUGARU
      STUDY).
AB  - AIM: The aim of this study was to clarify the rates of remission and progression
      for microalbuminuria in patients with type 2 diabetes (T2DM); and factors
      associated with remission and progression of diabetic nephropathy (DN). PATIENTS
      AND METHODS: T2DM patients with a urinary albumin excretion (UAE) rate of 30-300
      mg/gCr who were attending the medical clinic in the Tsugaru region in Japan were
      enrolled into this prospective, observational study for 36 months (N=317). We
      investigated the rate of remission (UAE <30 mg/g creatinine (Cr); normal
      albuminuria) and the rate of progression (UAE >=300 mg/gCr; overt proteinuria) 36
      months after study registration. RESULTS: The number of patients whose UAE levels
      were <30 mg/gCr (DN remission) at 36 months after registration was 64 (27.4%),
      and the number of patients whose UAE levels were >=300 mg/gCr (DN progression) at
      36 months after registration was 32 (13.7%). From multiple logistic regression
      analysis, the sole factor that contributed to remission at 36 months after
      registration was the UAE levels at registration (OR: 0.99; 95% CI: 0.98-1.00,
      p=0.003), and the factors that contributed to progression at 36 months after
      registration were the levels of UAE (OR: 1.01; 95% CI: 1.01-1.02, p=0.000) and
      systolic blood pressure (OR: 0.96; 95% CI: 0.93-1.00, p=0.033) at registration.
      CONCLUSION: Results suggest that patients with less severe microalbuminuria among
      microalbuminuric patients might more commonly experience DN remission and that
      earlier intervention is very important for promoting microalbuminuria remission
      in DN.

PMID- 28438852
TI  - The Use of Proteomics in Assisted Reproduction.
AB  - Despite the explosive increase in the use of Assisted Reproductive Technologies
      (ART) over the last 30 years, their success rates remain suboptimal. Proteomics
      is a rapidly-evolving technology-driven science that has already been widely
      applied in the exploration of human reproduction and fertility, providing useful
      insights into its physiology and leading to the identification of numerous
      proteins that may be potential biomarkers and/or treatment targets of a
      successful ART pregnancy. Here we present a brief overview of the techniques used
      in proteomic analyses and attempt a comprehensive presentation of recent data
      from mass spectrometry-based proteomic studies in humans, regarding all
      components of ARTs, including the male and female gamete, the derived zygote and
      embryo, the endometrium and, finally, the ART offspring both pre- and
      postnatally.

PMID- 28438855
TI  - The Effectiveness of Febrile Neutropenia Prophylaxis with Lipegfilgrastim in
      Routine Clinical Practice.
AB  - Febrile neutropenia (FN) is a common and potentially fatal complication of
      anticancer treatment, particularly in patients receiving myelosuppressive
      chemotherapy. It has been shown that prophylaxis with granulocyte colony
      stimulating factor (G-CSF), especially its pegylated forms, significantly reduces
      the incidence of FN, the likelihood of chemotherapy dose intensity reduction and,
      also, the number of hospitalizations due to FN. This review discusses currently
      published results from clinical trials dealing with FN prophylaxis in routine
      clinical practice in patients with solid tumors and myeloproliferative
      malignancies with a focus on lipegfilgrastim, which is the newest modification of
      the original molecule filgrastim. The discussed results proved that prophylactic
      administration of lipegfilgrastim can almost eliminate the risk of FN and
      significantly reduce the risk of chemotherapy (CHT) dose reduction in routine
      clinical practice in cases of a clear high-risk chemotherapy regimen or in the
      presence of risk factors (such as age, comorbidities, performance status, etc.)
      in patients who received chemotherapy with medium risk of FN.

PMID- 28438854
TI  - Laparoscopic Splenectomy for Benign Hematological Disorders in Adults: A
      Systematic Review.
AB  - BACKGROUND: Since its introduction in the early 1990s, laparoscopic splenectomy
      (LS) has gained worldwide acceptance for spleen removal, especially in
      hematological patients. AIM: The present review summarizes the current knowledge
      and results of LS for the treatment of benign hematological diseases in adults.
      MATERIALS AND METHODS: A MEDLINE/PubMed database research was performed using the
      terms: "laparoscopic splenectomy" OR "laparoscopy" OR "splenectomy" AND
      "hematological disorders" OR "hematological disease" OR "hematology" AND "adults"
      as key words. We set our analysis starting date as January 1st 2010 and the end
      date as December 31st 2016. We identified 247 relative articles. All the
      references from the identified articles were searched for relevant information.
      RESULTS: Twenty-seven articles were deemed appropriate for our analysis. LS was
      found to be feasible and safe in the majority of patients with benign
      hematological disorders, with a mortality rate ranging from 0% to less than 4%
      and the postoperative complications rate from 0% to 35.7%. The conversion rate
      was also very low (4%) and response (complete or partial) was achieved in more
      than 80% of patients. Lateral approach with four trocars was the most commonly
      used approach with concommitant cholecystectomy being correlated with increased
      operative time and morbidity. CONCLUSION: Current literature holds that whenever
      splenectomy is required for the treatment of hematological disorders in adults, a
      laparoscopic approach should be offered as the gold standard. However, to
      strengthen the clinical evidence in favor of LS, more high-quality clinical
      trials on several issues of the procedure are necessary.

PMID- 28438856
TI  - Tailoring the 'Perfect Fit' for Renal Transplant Recipients with End-stage
      Polycystic Kidney Disease: Indications and Timing of Native Nephrectomy.
AB  - BACKGROUND: The ideal timing of native nephrectomy in relation to kidney
      transplantation in patients with autosomal-dominant polycystic kidney disease
      (ADPKD) can be a very puzzling decision for transplant surgeons and remains a
      matter of debate. This review article aims to present current literature
      regarding this highly controversial issue. MATERIALS AND METHODS: The
      MEDLINE/PubMed database was searched using "polycystic kidney disease",
      "renal/kidney transplantation" and "native nephrectomy" as key words. Our search
      was focused on the optimal timing of and indications for native nephrectomy in
      renal transplant recipients with ADPKD. RESULTS: In symptomatic cases, pre
      transplant unilateral or bilateral native nephrectomy seems appropriate, in order
      to alleviate symptoms. In cases that are provided with the option of living-donor
      transplantation, the performance of the simultaneous procedure could be of
      benefit. When the principal indication of native nephrectomy is the creation of
      space for the renal allograft, various studies highlight the safety of the
      simultaneous approach of either unilateral or bilateral nephrectomy. CONCLUSION:
      No consensus exists on the appropriate timing for native nephrectomy in patients
      with ADPKD. Several issues to be addressed in the decision-making process are the
      importance of residual diuresis, the longer operative time along with the
      associated prolonged ischemia time and higher complication rate of the combined
      procedure.

PMID- 28438857
TI  - Reduced Competitive Repopulation Capacity of Multipotential Hematopoietic Stem
      Cells in the Bone Marrow of Friend Virus-infected Fv2-resistant Mice.
AB  - BACKGROUND/AIM: The polycythemia form of Friend leukemia virus (FVP) causes
      splenomegaly and lethal erythroleukemia in Fv-2s-susceptible mouse strains. We
      sought to determine whether the hematopoietic stem cell (HSC) pool was expanded
      in Fv-2r-resistant mice. MATERIALS AND METHODS: The 120-day bone marrow
      transplantation competitive repopulation assay was used to determine whether FVP
      infected Fv-2r C57BL/6 mice demonstrated expansion of the HSC pool compared to
      the pool of committed hematopoietic progenitor cells in the same marrow assayed
      in vitro. RESULTS: There was a significant expansion of committed hematopoietic
      progenitors observed in virus-infected Fv-2s FVB mice, but not Fv-2r C57BL/6
      mice. Furthermore, Fv-2r mice showed no detectable expansion of either committed
      hematopoietic progenitor cells or the multipotential stem cell pool by
      competitive repopulation assay. CONCLUSION: Friend virus disease in Fv-2s mice is
      associated with expansion of committed hematopoietic progenitors. Fv-2r mice show
      no expansion of either committed progenitor or pluripotential stem cell numbers.

PMID- 28438858
TI  - Functional Roles of Netrin-1 in Osteoblast Differentiation.
AB  - AIM: Recent studies have demonstrated that netrin-1 plays a vital role in bone
      metabolism. Previous studies have shown that osteoblasts produce netrin-1 which
      affects osteoclast differentiation. However, the role of netrin-1 in osteoblast
      differentiation is not well understood. In this study, we explored the roles of
      netrin-1 in osteoblasts. MATERIALS AND METHODS: Quantitative reverse
      transcriptase polymerase chain reaction (qPCR), RNA interference for netrin
      receptors, the generation of netrin-1 plasmid, transfection of plasmids, and cell
      proliferation assay were performed. RESULTS: During osteoblast differentiation by
      ascorbic acid, netrin-1 expression was significantly decreased. Gene expression
      related with osteoblast differentiation was down-regulated by netrin-1 treatment.
      We also found that osteoblast differentiation by bone morphogenetic protein-4
      (BMP-4) was inhibited in the presence of recombinant netrin-1. Forced expression
      of both BMP-4 and netrin-1 significantly decreased alkaline phosphatase
      expression. On the other hand, Unc5b, neogenin, and A2b which belong to netrin
      receptors were expressed by osteoblasts. Moreover, alkaline phosphatase
      expression was significantly decreased by knockdown for the combination of two
      receptors among these receptors. CONCLUSION: Netrin-1 is involved in the
      regulation of osteoblast differentiation.

PMID- 28438859
TI  - Automated Multichamber Time-lapse Videography for Long-term In Vivo Observation
      of Migrating Cells.
AB  - AIM: To observe and document the migration of living cells by time-lapse
      videography, we constructed a low-budget system based on a common inverted
      microscope. MATERIALS AND METHODS: Long-term observation of six-well plates is
      enabled through maintenance of cell culture conditions (5% CO2 in air at 37
      degrees C). Points of interest can be revisited in definable intervals with <1
      MUm repositioning error. Digital photographs from each programmed time point are
      paired with environmental data and combined into a record. RESULTS: We used this
      new chamber to observe the migration of various cell lines. The design represents
      a good compromise between low cost and good precision. Detailed analyses verified
      that the environmental conditions were appropriately maintained, enabling long
      term observation of viable cells. The stimulating influence of irradiation with
      photons (radiotherapy) on cellular motility of glioblastoma cells is presented.
      CONCLUSION: This study demonstrates that useful videographic systems can be
      constructed at low cost.

PMID- 28438860
TI  - Bone Regeneration of Hydroxyapatite with Granular Form or Porous Scaffold in
      Canine Alveolar Sockets.
AB  - This study was undertaken to assess bone regeneration using hydroxyapatite (HA).
      The primary focus was comparison of bone regeneration between granular HA (gHA)
      forms and porous HA (pHA) scaffold. The extracted canine alveolar sockets were
      divided with three groups: control, gHA and pHA. Osteogenic effect in the gHA and
      pHA groups showed bone-specific surface and bone mineral density to be
      significantly higher than that of the control group (p<0.01). Bone volume
      fraction, bone mineral density, and amount of connective tissue related to
      disturbing osseointegration of the gHA group was higher than in the pHA group.
      Quantity of new bone formation of the pHA group was higher than that of the gHA
      group. This study demonstrated that gHA and pHA are potentially good bone
      substitutes for alveolar socket healing. For new bone formation during 8 weeks'
      post-implantation, HA with porous scaffold was superior to the granular form of
      HA.

PMID- 28438861
TI  - Vitamin C Improves Therapeutic Effects of Adipose-derived Stem Cell
      Transplantation in Mouse Tendonitis Model.
AB  - BACKGROUND/AIM: We hypothesized that combined therapy using adipose-derived stem
      cells (ASCs) and vitamin C might improve tendon regeneration in tendonitis. To
      determine combined effects of ASC transplantation with vitamin C, we used
      senescence marker protein 30 (SMP30)-knockout (KO) mice that cannot biosynthesize
      vitamin C by themselves. MATERIALS AND METHODS: SMP30-KO were divided into four
      groups: Control, vitamin C, ASCs, and vitamin C plus ASCs. Tendonitis was induced
      in the achilles tendons via injection of collagenase type I. After 1 week, ASCs
      were injected into the intratendonal region. After 30 days, all mice were
      sacrificed and Achilles tendons were isolated. RESULTS: Gross and microscopic
      findings showed mice treated with combination of ASC transplantation and vitamin
      C showed better tendon regeneration than those in other groups. This combination
      led to higher serum vitamin C levels than use of vitamin C alone. This indicates
      that the vitamin C-treated group used more vitamin C as a precursor to collagen
      synthesis, whereas vitamin C was in excess in the combination group because of
      the added effect of ASCs on tendon healing. CONCLUSION: This study showed that
      vitamin C improved the effect of ASC transplantation on tendonitis by inducing a
      better stem cell niche.

PMID- 28438862
TI  - Anti-inflammatory Effects of Oct4/Sox2-overexpressing Human Adipose Tissue
      derived Mesenchymal Stem Cells.
AB  - BACKGROUND/AIM: The transcription factors Oct4 and Sox2 enhance the proliferation
      and pluripotency of human adipose tissue-derived mesenchymal stem cells (hAT
      MSCs); however, the anti-inflammatory effects of Oct4- and Sox2-overexpressing
      hAT-MSCs (Oct4/Sox2-hAT-MSCs) are unclear. Here, we evaluated the anti
      inflammatory effects of Oct4/Sox2-hAT-MSCs in vitro and in vivo. MATERIALS AND
      METHODS: Supernatants from green-fluorescent protein (GFP)- and Oct4/Sox2-hAT
      MSCs were used to treat lipopolysaccharide (LPS)-stimulated RAW264.7 cells and
      inflammatory cytokine expression was determined. In LPS-induced mice, GFP- and
      Oct4/Sox2-hAT-MSCs were injected intraperitoneally and survival rates, as well as
      sickness scores of mice, were monitored. RESULTS: Decreased expression of pro
      inflammatory cytokines was observed in Oct4/Sox2-hAT-MSC supernatant-exposed
      RAW264.7 cells compared to that in GFP-hAT-MSC supernatant-exposed RAW264.7
      cells. The sickness score was reduced to 34.9% and the survival rate was
      increased by 11.1% in Oct4/Sox2-hAT-MSC-injected mice compared to that in GFP-hAT
      MSC-injected mice. CONCLUSION: Our findings provide important insights into the
      development of therapies utilizing Oct4/Sox2-hAT-MSCs in inflammatory diseases.

PMID- 28438863
TI  - The Role of p16 and MDM2 Gene Polymorphisms in Prolactinoma: MDM2 Gene
      Polymorphisms May Be Associated with Tumor Shrinkage.
AB  - AIM: Prolactinomas are thought to arise from clonal expansion of a single mutated
      cell which is subjected to growth stimuli of several permissive factors, although
      the pathogenetic mechanisms underlying tumorigenesis remain unclear. The present
      study aimed to investigate the role of p16 (540C->G and 580C->T) and mouse double
      minute 2 (MDM2) (SNP309T->G) gene polymorphisms in tumorigenesis and
      characteristics of prolactinoma. PATIENTS AND METHODS: A total of 74 patients
      with prolactinoma and 100 age- and gender-matched healthy individuals were
      enrolled in the study. Serum prolactin levels were measured by enzyme-linked
      immunosorbent assay (ELISA). p16 and MDM2 polymorphisms were determined by
      polymerase chain reaction-restriction fragment polymorphism and agarose gel
      electrophoresis. RESULTS: p16 540C->G genotype distribution was found to be: CC:
      66.2%, CG: 28.4%, GG: 5.4%; p16 580C->T genotype distribution was found to be:
      CC: 82.4%, CT: 17.6%, TT: 0% and MDM2 genotype distribution was found to be: TT:
      31.1%, TG: 47.3%, GG: 21.6% in patients with prolactinoma. Tumor diameter before
      treatment was correlated with prolactin levels before treatment and percentage of
      prolactin decrease with treatment (r=0.719, p<0.001, p=0.034 r=0.256,
      respectively). The number of patients with tumor size decrease of more than 50%
      in those with homozygous genotype (TT+GG) of MDM2 SNP309T->G was significantly
      higher than in heterozygous genotype (TG) carriers (odds ratio(OR)=0.18, 95%
      confidence interval(CI)=0.06-0.58; p=0.003). CONCLUSION: This study showed that
      p16 and MDM2 polymorphisms do not play a decisive role in tumorigenesis, but some
      genotypes of these polymorphisms might be associated with follow-up
      characteristics of prolactinoma.

PMID- 28438864
TI  - Partial Deletions of Y-Chromosome in Infertile Men with Non-obstructive
      Azoospermia and Oligoasthenoteratozoospermia in a Turkish Population.
AB  - Many genetic alterations have been identified to aid in understanding the genetic
      basis of male infertility, however, the cause of 30% of male infertility remains
      unknown. Some studies indicated that subdeletions of Y chromosome may be a reason
      for male infertility caused by testicular failure. In this regard, we aimed to
      investigate frequency of AZFc region subdeletions and their clinical effects in
      patients with idiopathic infertility. A total of 333 male infertile patients with
      non-obstructive azoospermia (NOA) or oligoasthenoteratozoospermia (OAT), and 87
      normozoospermic controls were screened to detect gr/gr, b1/b3 and b2/b3
      subdeletions. We recorded higher gr/gr deletion frequency in normozoospermic
      controls compared NAO and OAT groups (p=0.026). There were no significant
      differences in b2/b3 subdeletion rates among groups (p=0.437). In the OAT group,
      follicle-stimulating hormone levels of cases with b2/b3 deletion were
      statistically lower than cases without b2/b3 deletion (p=0.047). No statistical
      correlations were indicated among subdeletions, sperm count and assisted
      reproductive technology (ART) outcomes. These data demonstrate that gr/gr and
      b2/b3 subdeletions may not play a significant role in the etiopathogenesis of
      male infertility and ART outcomes in the studied population.

PMID- 28438865
TI  - Effect of Hydrogen Dioxide Treatment on the Osteogenic Potential of Duck-beak
      Bone-derived Natural Bioceramic Microparticles.
AB  - BACKGROUND/AIM: As an alternative material to the autogenous bone, duck-beak bone
      particle for bone substitute have been attracting great attention due to their
      biological properties. To deliver the most favorable outcome of medical
      treatment, it is essential to study the effect of various processing methods of
      the duck-beak bone. In this study, we compared the two deproteinizing agents for
      manufacturing duck-beak bone. Group 1 was treated by a conventional chemical
      agent (ethylenediamine) and Group 2 by hydrogen dioxide (H2O2). In vitro and in
      vivo experiments were conducted in parallel to compare the cytocompatibility and
      osteogenic capability between two processing methods. For in vitro tests, human
      adipose-derived mesenchymal stem cells (hAD-MSCs) were planted onto each sample
      and their attachment and growing were evaluated. For in vivo biocompatibility and
      osteogenic properties, the samples were applied on the critical-sized calvarial
      bone defect of rats. Group 2 showed significantly higher cell attachment but
      Group1 showed slightly higher cell proliferation. In in vivo tests, all groups
      have shown biocompatibility and increased level of osteogenic potential. However,
      Group 2 had significantly higher bone regeneration (p<0.05). This experiment
      confirmed that H2O2 can be an optimal processing method for duck-beak bone
      particle.

PMID- 28438867
TI  - Magnetic Resonance Imaging Assessment of Lipomatous Soft-tissue Tumors.
AB  - AIM: To establish the accuracy of magnetic resonance imaging (MRI) in
      distinguishing between benign and malignant lipomatous tumors; to evaluate the
      reproducibility of the MRI interpretation assessing the agreement between
      judgments of two radiologists with the same experience in soft-tissue sarcomas;
      to identify an association among MRI findings (size, depth, septa, nodules,
      signal homogeneity) and nature of the lesion. MATERIALS AND METHODS: A total of
      54 patients (28 men and 26 women), with a mean age of 56 (range=27-84) were
      included years. All subjects followed-up by the Multidisciplinary Sarcoma Group.
      The following MRI findings were judged in a blind study by two radiologists:
      size, localization, septa, nodules and signal homogeneity. A diagnostic
      indication was then given from among lipoma, atypical lipomatous tumour (ALT) and
      liposarcoma. Accuracy in distinguishing between benign and malignant lesions, and
      between lipoma and ALT (Fisher's exact test), inter-operator agreement (Cohen's
      kappa), association of MRI findings and malignancy of the lesion (Fisher's exact
      test and odds ratio) were evaluated. RESULTS: The inter-operator agreement was
      complete (100%). The agreement between diagnostic hypothesis and histological
      diagnosis was statistically significant (p<0.05). Among the radiological findings
      taken into account, only septa and signal homogeneity were significantly
      associated with the malignancy of the lesion (p<0.05). CONCLUSION: MRI could be
      helpful in distinguishing lipomatous tumors, allowing biopsy to be avoided in
      some cases (negative predictive value=100%).

PMID- 28438868
TI  - Survival and Predictors of Death for Patients with Bronchopulmonary Carcinoid at
      a Danish Tertiary NET Centre.
AB  - BACKGROUND/AIM: Bronchopulmonary carcinoids comprise of typical carcioids (TC)
      and atypical carcinoids (AC). We present characteristics and associated mortality
      in patients with TC and AC followed-up at a Danish NET Centre between 2000-2014.
      PATIENTS AND METHODS: Data were obtained from medical records, computed
      tomographic scans, and pathology reports. Mortality was investigated by Kaplan
      Meier survival analysis. RESULTS: We included 68 patients, 55 with TC (81%) and
      13 with AC (19%). Median follow-up was 5.6 years (range=1.0-26.3). Fourteen
      patients died; 13 were smokers, and nine had a Ki67 index >2%. Metastatic
      disease, smoking and male gender were significantly associated with risk of dying
      within the first 5 years (log-rank, all p<0.05), while Ki67 index >2% showed a
      trend for being associated with risk of death (p=0.11). CONCLUSION: Survival is
      strongly associated with tumor type and current/previous smoking. Metastatic
      disease at diagnosis and male gender are predictors of death within 5 years.

PMID- 28438866
TI  - Soluble Urokinase-type Plasminogen Activator Receptor Predicts All-cause 5-Year
      Mortality in Ischemic Stroke and TIA.
AB  - AIM: We evaluated soluble urokinase-type plasminogen activator receptor (suPAR)
      levels in different stroke subtypes and assessed their prognostic value regarding
      5-year outcomes. MATERIALS AND METHODS: The study included 117 stroke patients
      (81 males; mean=age 61+/-11 years) with suspected cardioembolic stroke whose
      plasma suPAR concentration was assessed. Altogether, 20 (17.1%) patients suffered
      from stroke as a result of cardioembolism, 12 (10.3%) from large-artery
      atherosclerosis, 9 (7.7%) from small-vessel disease, 11 (9.4%) from both large
      artery and cardioembolic etiology, and 65 (55.6%) had cryptogenic stroke. The
      mean follow-up period was 5 years. RESULTS: suPAR concentration was higher in
      patients who suffered from stroke/transient ischemic attack due to large-artery
      atherosclerosis (3.2+/-0.9 ng/ml) compared to small-vessel disease (2.0+/-0.5
      ng/ml, p<0.001). An elevated plasma suPAR concentration was associated with all
      cause mortality during the follow-up period (p=0.003). CONCLUSION: Elevated
      plasma suPAR concentrations predicted all-cause mortality during the 5-year
      follow-up after ischemic stroke. suPAR was not able to differentiate patients
      with cardioembolic stroke from those with other stroke types.

PMID- 28438869
TI  - Correlation Between Expression of the Cancer/Testis Antigen KK-LC-1 and
      Helicobacter pylori Infection in Gastric Cancer.
AB  - BACKGROUND/AIM: Our previous study indicated that Kita-kyushu lung cancer antigen
      1 (KK-LC-1) is a cancer/testis antigen (CTA) expressed in 82% of gastric cancer
      cases. Here, we investigated the relationship between KK-LC-1 expression and
      Helicobacter pylori infection in Japanese patients with gastric cancer. PATIENTS
      AND METHODS: We examined CTA expression in 25 surgical gastric cancer specimens
      and anti-H. pylori IgGs in the serum of each patient. RESULTS: KK-LC-1 was
      expressed in 80% of tumor samples, markedly higher than melanoma antigen gene
      (MAGE)-A1, MAGE-A3, MAGE-A4, synovial sarcoma, X breakpoint 4 (SSX4) and New York
      esophageal squamous cell carcinoma-1 (NY-ESO-1). Anti-H. pylori IgG titers from
      the KK-LC-1-positive patients were significantly higher (67.5+/-7.6) than those
      from KK-LC-1-negative patients (15.8+/-7.5, p<0.01) although there were no
      significant differences between patients positive and negative for MAGE-A1, -A3
      and-A4, SSX4 and NY-ESO-1. CONCLUSION: As far as we are aware, this is the first
      report of a correlation between a carcinogen and CTA expression in clinical
      samples. KK-LC-1 was frequently expressed in gastric cancer caused by H. pylori
      infection. The risk diagnosis for gastric cancer might be more accurate if KK-LC
      1 expression status were also considered.

PMID- 28438870
TI  - Clinical Implication of the Width of Subserosal Invasion in T3N0 Gastric Cancer.
AB  - BACKGROUND: The aim of this study was to clarify the impact of the horizontal
      width of tumor invasion into the subserosal layer on prognosis in patients with
      T3N0 gastric cancer. PATIENTS AND METHODS: A total of 72 patients with T3N0
      cancer were enrolled. Relapse-free survival of the subgroups classified according
      to width of subserosal invasion was compared to that of 34 patients with T4aN0
      cancer. RESULTS: The group with wide invasion (>=1.5 cm) had a significantly
      poorer prognosis than those with narrow invasion (<1.5 cm) (p=0.014).
      Multivariate analysis revealed the width of subserosal invasion to be an
      independent prognostic factor. There was no significant difference between the
      T3N0 group with wide invasion and the T4aN0 group in the prognosis and recurrent
      status. CONCLUSION: The malignant potential of T3N0 gastric cancer with wide
      subserosal invasion was found to be similar to that of T4aN0 cancer.

PMID- 28438871
TI  - Multiparametric MRI Apparent Diffusion Coefficient (ADC) Accuracy in Diagnosing
      Clinically Significant Prostate Cancer.
AB  - AIM: To evaluate the accuracy of multiparametric magnetic resonance imaging
      apparent diffusion coefficient (mpMRI ADC) in the diagnosis of clinically
      significant prostate cancer (PCa). PATIENTS AND METHODS: From January 2016 to
      December 2016, 44 patients who underwent radical prostatectomy for PCa and mpMRI
      lesions suggestive of cancer were retrospectively evaluated at definitive
      specimen. The accuracy of suspicious mpMRI prostate imaging reporting and data
      system (PI-RADS >=3) vs. ADC values in the diagnosis of Gleason score >=7 was
      evaluated. RESULTS: Receiver operating characteristics (ROC) curve analysis gave
      back an ADC threshold of 0.747*10-3 mm2/s to separate between Gleason Score 6 and
      >=7. The diagnostic accuracy of ADC value (cut-off 0.747*10-3 mm2/s) vs. PI-RADS
      score >=3 in diagnosing PCa with Gleason score >=7 was equal to 84% vs. 63.6%
      with an area under the curve (AUC) ROC of 0.81 vs. 0.71, respectively.
      CONCLUSION: ADC evaluation could support clinicians in decision making of
      patients with PI-RADS score <3 at risk for PCa.

PMID- 28438872
TI  - Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal
      Liver Metastases.
AB  - BACKGROUND: Surgical resection is currently considered the only potentially
      curative option as a treatment strategy of colorectal liver metastases (CRLM).
      However, the criteria for selection of resectable CRLM are not clear. The aim of
      this study was to confirm a new prognostic indicator of CRLM after hepatic
      resection. PATIENTS AND METHODS: One hundred thirty nine patients who underwent
      initial surgical resection from 1994 to 2015 were investigated retrospectively.
      Prognostic factors of overall survival including the product of maximum diameter
      and number of metastases (MDN) were analyzed. RESULTS: Primary tumor
      differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally
      resectable metastases, H score, grade of liver metastases, resection with non
      curative intent and MDN were found to be prognostic factors of overall survival
      (OS). In multivariate analyses of clinicopathological features associated with
      OS, MDN and non-curative intent were independent prognostic factors. Patients
      with MDN >=30 had shown significantly poorer prognosis than patients with MDN <30
      in OS and relapse-free survival (RFS). CONCLUSION: MDN >=30 is an independent
      prognostic factor of survival in patients with CRLM and optimal surgical
      criterion of hepatectomy for CRLM.

PMID- 28438873
TI  - Angiotensin-converting Enzyme Inhibition Improves the Effectiveness of
      Transcutaneous Carbon Dioxide Treatment.
AB  - AIM: To study the effect of carbon dioxide (CO2) therapy on the nitric oxide (NO)
      pathway by monitoring plasma asymmetric dimethylarginine (ADMA) concentrations.
      PATIENTS AND METHODS: Forty-seven hypertensive patients who underwent
      transcutaneous CO2 therapy were enrolled. Thirty healthy individuals were
      recruited for the control group. Blood samples were taken one hour before, as
      well as one hour, 24 hours and 3 weeks after the first CO2 treatment. Controls
      did not undergo CO2 treatment. Plasma ADMA levels were measured by ELISA.
      RESULTS: ADMA levels decreased significantly one hour after the first CO2
      treatment compared to the baseline concentrations (p=0.003). Significantly
      greater reduction was found among patients in whom angiotensin converting enzyme
      inhibitors (ACEIs) were administered (p=0.019). CONCLUSION: The short- and long
      term decrease of ADMA levels suggests that CO2 is not only a vasodilator, but
      also has a beneficial effect on the NO pathway. ACE inhibition seems to enhance
      the effect of CO2 treatment.

PMID- 28438874
TI  - Partial Cystectomy for Atypical Isolated Recurrence of Ovarian Adenocarcinoma - A
      Case Report and Literature Review.
AB  - BACKGROUND: Most cases with advanced-stage epithelial ovarian malignancies will
      experience recurrent disease at a certain moment of their evolution, even if
      maximal cytoreductive surgery has been performed at the moment of initial
      diagnosis. However, it seems that the best therapeutic strategy, in case of
      relapse, remains aggressive re-resection, with complete cytoreduction being the
      most efficient way to improve survival. MATERIALS AND METHODS: We present the
      case of a 55-year-old patient diagnosed with an isolated pelvic recurrence after
      stage IIIC surgically-treated ovarian cancer three years after primary
      cytoreduction. RESULTS: Intraoperatively, the diagnosis of an isolated pelvic
      recurrence invading the urinary bladder was confirmed. The recurrent tumor was
      resected en bloc with partial cystectomy. The postoperative course was
      uneventful, while histopathological studies confirmed the presence of a poorly
      differentiated epithelial ovarian recurrent adenocarcinoma. At two year follow
      up, the patient is free of any recurrent disease. CONCLUSION: Isolated pelvic
      recurrences after surgically-treated ovarian adenocarcinomas can be safely
      removed and might improve survival.

PMID- 28438875
TI  - A New Prognostic Instrument Specifically Designed for Patients Irradiated for
      Recurrent Carcinoma of the Bladder.
AB  - BACKGROUND/AIM: To develop an instrument that could estimate the 1-year survival
      probabilities of patients irradiated for recurrent carcinoma of the bladder.
      PATIENTS AND METHODS: Thirty patients irradiated for locally recurrent bladder
      carcinoma were included. Six pre-treatment factors [age, gender, Karnofsky score
      (KPS), pack years, grading and time between cancer diagnosis and radiotherapy]
      were evaluated for survival. Of those factors showing a trend or significance on
      multivariate analysis, 1-year survival rates were added. RESULTS: On multivariate
      analysis, KPS was significant (hazard ratio(HR)=3.76, p=0.008), age showed a
      trend (HR=2.04, p=0.13). Patient scores were five, nine, ten or fourteen points
      with 1-year survival rates of 13%, 25%, 57% and 82% (p=0.003). Three groups were
      designed, A (5-9 points), B (10 points) and C (14 points) with 1-year survival
      rates of 17%, 57% and 82% (p=0.001). CONCLUSION: This score, including three
      groups with different 1-year survival probabilities, can aid physicians treating
      patients with recurrent bladder carcinoma.

PMID- 28438876
TI  - Thrombotic Microangiopathy Following Chemotherapy with S-1 and Cisplatin in a
      Patient with Gastric Cancer: A Case Report.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) represents a spectrum of serious
      disorders characterized by occlusive microvascular thrombosis, thrombocytopenia
      and end-organ damage. TMA is associated with a broad range of conditions and is
      also a well-described complication of both cancer and its treatment. CASE REPORT:
      A 77-year-old Japanese woman underwent S-1 and cisplatin chemotherapy for
      treatment of advanced gastric cancer with multiple lymph node and liver
      metastases. She was found with severe anemia and thrombocytopenia during the
      third course of chemotherapy. She was diagnosed with TMA based on
      thrombocytopenia, schistocytosis, hemolytic anemia and renal dysfunction. She
      underwent treatment with plasmapheresis; however, her response to treatment was
      poor and died on day 16 of hospitalization. The autopsy performed revealed
      microthrombi in the glomeruli and tubulonecrosis in the kidneys. CONCLUSION: This
      is the first case report of TMA in association with the use of S-1 and cisplatin.
      Therapists have to take account of TMA when using S-1 and cisplatin treatment.

PMID- 28438877
TI  - IT-based Psychosocial Distress Screening in Patients with Sarcoma and Parental
      Caregivers via Disease-specific Online Social Media Communities.
AB  - BACKGROUND: Psychosocial distress can be frequently observed in patients with
      sarcoma, depicting a relevant clinical problem. However, prospective data
      collection on psychosocial distress in patients with rare tumors is often time
      consuming. In this context, social media such as Facebook can serve as a
      potential platform to expand research. The aim of this study was to assess the
      feasibility of psychosocial distress screening in patients with osteosarcoma and
      Ewing's sarcoma via social media. MATERIALS AND METHODS: For this study an online
      questionnaire including general information and self-assessment distress
      measurement tools for patients and parents was created. The link to the
      questionnaire was then posted on the main page of the two largest disease
      specific Facebook communities on osteosarcoma and Ewing's sarcoma. RESULTS:
      Within 2 months, 28 patients and 58 parents of patients were enrolled. All
      patients with osteosarcoma and Ewing's sarcoma, as well as the majority of
      parental caregivers of such patients, showed relevant psychosocial distress
      levels. CONCLUSION: Crowdsourcing via disease-specific patient communities on
      Facebook is feasible and provides great potential for acquisition of medical data
      of rare diseases.

PMID- 28438878
TI  - Surgical Management of Non-small Cell Lung Cancer with Solitary Hematogenous
      Metastases.
AB  - BACKGROUND/AIM: The treatment of patients with solitary hematogenous metastases
      from non-small cell lung cancer (NSCLC) remains controversial, although numerous
      retrospective studies have reported favorable results for patients offered
      combined surgical therapy. Our aim was to determine the role of surgical
      resection in the management of NSCLC with solitary extrapulmonary metastases and
      to investigate for possible prognostic factors. PATIENTS AND METHODS: Between
      January 2004 and December 2012, 12 patients with NSCLC, from two Institutions,
      underwent metastasectomy for their solitary metastatic lesion. Sites of
      metastases included brain (n=3), adrenal gland (n=6), thoracic wall (n=2) and
      diaphragm (n=1). All patients had undergone pulmonary resections for their
      primary NSCLC. RESULTS: Median survival for the entire cohort was 24.1 months,
      whereas 1- and 5-year survival rates were 73% and 39%, respectively. Patients
      with stage III intrathoracic disease had significantly worse survival than those
      with lower tumor stage. A tendency for adenocarcinomatous histology to positively
      affect survival was recognized, although it was proven not to be statistically
      significant. CONCLUSION: Despite the retrospective nature of our study and the
      small cohort size, it is emerging that combined surgical resection might offer
      patients with NSCLC with solitary hematogenous metastases a survival benefit.
      Limited intrathoracic disease and adenocarcinomatous histology might be
      associated with better outcomes.

PMID- 28438879
TI  - Definitive Intensity-modulated Radiation Therapy in Elderly Patients with Locally
      Advanced Oropharyngeal Cancer.
AB  - BACKGROUND: To evaluate the treatment tolerance and clinical outcomes in patients
      aged 70 years and older with locally advanced oropharyngeal cancer treated by
      definitive intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: We
      retrospectively analyzed 15 consecutive elderly patients, with histologically
      proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without
      involved lymph nodes at diagnosis, who received definitive sequential IMRT (70
      Gy; 2 Gy/fraction). Adult Comorbidity Evaluation-27 (ACE-27) score was calculated
      and its influence on treatment tolerance and clinical outcomes was analyzed.
      RESULTS: A total of 15 patients were included with a median age of 77 years
      (range=70-88 years). At baseline, 8 patients (53.3%) had an ACE-27 score of 1,
      and the remainder (n=7, 46.7%) had a comorbidity index of 0. All patients
      completed programmed IMRT treatment, without any reduction of total dose. Oral
      pain and mucositis were the most common acute side-effects, classified as grade 3
      in 6 patients (40%) only. Xerostomia was reported in 13 patients (86.7%), without
      severe manifestation. There was no hematological toxicity. ACE-27 score was not
      related to higher severe acute toxicity. No patients experienced grade 3 or more
      late toxicity. Five-year overall survival and disease-free survival rates were
      63.6% (95% confidence interval=32.7-83.3%) and 55% (95% confidence interval=24.4
      77.6%), respectively. Comorbidity score did not influence survival outcomes, both
      overall survival (p=0.46) and disease-free survival (p=0.55). CONCLUSION:
      Treatment tolerance, as well as survival outcomes were good in elderly
      oropharyngeal cancer patients treated with definitive sequential IMRT. Due to age
      and comorbidity, no dose or volume reduction for IMRT should be considered in
      this setting of patients. A prospective randomized trial with a large sample size
      should be conducted to confirm our results.

PMID- 28438880
TI  - Testicular Dose During Prophylaxis of Heterotopic Ossification with Radiation
      Therapy.
AB  - AIM: A single-institution, retrospective study was performed to investigate
      potential techniques to minimize radiation exposure to the testicles during
      heterotopic ossification (HO) prophylaxis. We report the impact of split-beam
      technique (SBT) and different photon energies on the total dose of radiation
      received by the testicles during prophylaxis of HO. MATERIALS AND METHODS:
      Between 2008 and 2010, we identified 64 patients with traumatic acetabular
      fractures who underwent surgery followed by radiation therapy (RT) without
      testicular shielding. Postoperative RT was delivered within 72 h in a single
      fraction of 700 cGy using 6-18 MV photons, without testicular shielding due to
      patient refusal. All patients underwent 3-D RT planning in which the testicles
      were contoured as a region of interest and dose-volume histograms (DVH) were
      generated. Additional treatment planning trials were created for each patient by
      utilizing a SBT medially and by using different photon energies (6, 10 and 18 MV)
      to study the effects of these maneuvers on the delivered dose to the testicles.
      RESULTS: In reviewing the DVH, it was noted that the mean dose delivered to the
      testicles was 10 cGy (range=3-40). The maximum dose was 31 cGy (range=7-430).
      When SBT was utilized, a significant reduction in the mean (44%) and maximum
      (47%) doses delivered to the testicles was noted. Further reductions in the mean
      (26%) and maximum (14%) doses were achieved by using higher-energy (10-18 MV)
      beams. The radiation doses to the testicles from the CT simulation and the two
      portal images were estimated to be 4 and 1.5 cGy, respectively. CONCLUSION: Low
      dose prophylactic RT to prevent HO around the hip causes a low, but likely
      biologically meaningful, radiation dose to be delivered to the testicles. This
      dose could be further reduced by using a medial SBT and photon energies above 6
      MV. Testicular shielding should be offered to all male patients receiving such
      RT. In addition, all patients should be informed about the consequences of
      testicular radiation as part of their informed consent.

PMID- 28438881
TI  - Prevalence of Congenital Cytomegalovirus Infection Assessed Through Viral Genome
      Detection in Dried Blood Spots in Children with Autism Spectrum Disorders.
AB  - BACKGROUND/AIM: Autism spectrum disorders (ASD) are neurodevelopmental disorders
      without a definitive etiology in most cases. Environmental factors, such as viral
      infections, have been linked with anomalies in brain growth, neuronal
      development, and functional connectivity. Congenital cytomegalovirus (CMV)
      infection has been associated with the onset of ASD in several case reports. The
      aim of this study was to evaluate the prevalence of congenital CMV infection in
      children with ASD and in healthy controls. PATIENTS AND METHODS: The CMV genome
      was tested by polymerase chain reaction (PCR) on dried blood spots collected at
      birth from 82 children (38 with ASD and 44 controls). RESULTS: The prevalence of
      congenital CMV infection was 5.3% (2/38) in cases and 0% (0/44) in controls
      (p=0.212). CONCLUSION: The infection rate was about 10-fold higher in patients
      with ASD than in the general Italian population at birth. For this reason,
      detection of CMV-DNA on dried blood spots could be considered in the work-up that
      is usually performed at ASD diagnosis to rule-out a secondary form. Given the
      potential prevention and treatment of CMV infection, this study could have
      intriguing consequences, at least for a group of patients with ASD.

PMID- 28438882
TI  - Rebiopsy of Histological Samples in Pretreated Non-small Cell Lung Cancer:
      Comparison Among Rebiopsy Procedures.
AB  - AIM: The aim of the present study was to compare successful rate, failure
      reasons, and complications among procedures of histological rebiopsy. PATIENTS
      AND METHODS: We retrospectively reviewed medical records of histologically
      rebiopsied cases with non-small cell lung cancer. RESULTS: One hundred and eleven
      histological rebiopsies were performed in: 86 (77%) lung; 11 (10%) lymph node; 5
      (5%) pleura; 4 (4%) liver; 2 (2%) muscle; 2 (2%) adrenal gland; and 1 (1%) rib.
      Successful rate by computed tomography-guided biopsy (CTGB), transbronchial
      biopsy (TBB), and ultrasound-guided biopsy were 86% (48/56), 90% (28/31), and
      100% (24/24), respectively. Reasons for rebiopsy failure by CTGB were
      no/insufficient malignant cells (n=5) and pneumothorax (n=3), and those by TBB
      were no/insufficient malignant cells (n=2) and bleeding (n=1). Severe
      complications (>=grade 3): one grade 3 pneumothorax and one grade 4 air
      embolization were observed in two (2%, 2/111) cases receiving CTGB. CONCLUSION:
      Rebiopsy of histological samples can be highly successful and feasible by optimal
      procedural selection.

PMID- 28438883
TI  - Ewing's Sarcoma Family Tumors in the Jaws: Case Report, Immunohistochemical
      Analysis and Literature Review.
AB  - Due to the low incidence of the Ewing's Sarcoma (ES) family tumors, the available
      epidemiology is likely to be unreliable, and at present, there are no standard
      diagnostic or clinical guidelines outlining their management. This report
      describes a case of peripheral primitive neuroectodermal tumor (ES/pPNET) which
      initially mimicked cystic lesions, and describes a comparison between ES and
      ES/pPNET in the jaws by the World Health Organization classification. This review
      addressed 63 cases published in the English literature between 1950 and 2016. The
      majority of cases were ES. Both ES and ES/pPNET mimicked other benign entities
      such as traumatic, cystic and inflammatory lesions. The patients who died of
      their disease had a history of metastatic tumors, and primary tumor located in
      the mandible and maxilla for ES and ES/pPNET, respectively. The differentiation
      of the ES family tumors from other small blue-cell tumors may be difficult and
      requires familiarity with histological and immunohistochemical features.

PMID- 28438884
TI  - Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2
      Positive Advanced Breast Cancer.
AB  - BACKGROUND/AIM: Tolerability and safety of trastuzumab emtansine (T-DM1) was
      investigated in Japanese patients with HER2-positive advanced breast cancer who
      were previously treated with chemotherapy and trastuzumab. PATIENTS AND METHODS:
      Patients with inoperable or recurrent breast cancer who were previously treated
      with chemotherapy and trastuzumab in adjuvant and/or metastatic disease were
      included. T-DM1 3.6 mg/kg was administered intravenously every 21 days. The
      administration dosage or schedule of T-DM1 was modified based on laboratory tests
      on the administration day. RESULTS: Among 232 patients analyzed, adverse events
      were reported in 228 patients (98.3%); five patients (2.2%) discontinued due to
      adverse events and twenty patients (8.6%) had serious adverse events. The most
      commonly reported grade >=3 adverse event of special interest was
      thrombocytopenia (69 patients; 29.7%), followed by hepatotoxicity (26 patients;
      11.2%). CONCLUSION: T-DM1 was well tolerated in Japanese patients with HER2
      positive advanced breast cancer and no new safety signals were observed.

PMID- 28438886
TI  - What If She Were My Friend?

PMID- 28438885
TI  - Prognostic Nomograms Stratify Survival of Patients with Hepatocellular Carcinoma
      Without Portal Vein Tumor Thrombosis After Curative Resection.
AB  - BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) without
      portal vein tumor thrombosis (PVTT) after curative resection is at variance. We
      identified the risk factors of poor postoperative prognosis and consequently
      developed prognostic nomograms generating individual risk of death and recurrence
      for this subgroup of patients with HCC. METHODS: The risk factors were identified
      and nomograms were developed based on a retrospective study of 734 patients in
      the primary cohort who underwent curative resection for HCC from 2010 to 2012.
      The predictive accuracy and discriminative ability of the nomograms were
      determined by concordance index (C-index) and calibration curve and compared with
      traditional staging systems of HCC. The results were validated in an independent
      cohort of 349 patients operated at the same institution in 2007. RESULTS: All of
      the independent factors for survival in multivariate analysis in the primary
      cohort were selected into the nomograms. The calibration curve for probability of
      survival showed good agreement between prediction by nomograms and actual
      observation. The C-indices of the nomograms for predicting overall survival and
      recurrence-free survival were 0.755 (95% confidence interval [CI], 0.752-0.758)
      and 0.665 (95% CI, 0.662-0.668), respectively, which were statistically higher
      than the C-indices of other HCC prognostic models. The results were further
      confirmed in the validation cohort. CONCLUSION: The proposed nomograms resulted
      in more accurate prognostic prediction for patients with HCC without PVTT after
      curative resection. The Oncologist 2017;22:561-569 IMPLICATIONS FOR PRACTICE:
      Hepatocellular carcinoma (HCC) poses a great therapeutic challenge due to the
      poor prognosis in patients underwent surgical resection. The portal vein tumor
      thrombosis (PVTT) as a robust risk factor for survival has been routinely
      integrated to staging systems. Nonetheless, the prognosis stratification for
      patients without PVTT was neglected to some extent. Herein, independent risk
      factors of OS and RFS in HCC patients without PVTT were reconfirmed. A predictive
      nomogram was constructed on these risk factors and was demonstrated to be a more
      accurate predictive model in HCC patients without PVTT, compared with the
      traditional staging systems.

PMID- 28438887
TI  - A Systematic Review of Strategies to Prevent Cisplatin-Induced Nephrotoxicity.
AB  - INTRODUCTION: Cisplatin, a platinum-based antineoplastic agent, is the
      cornerstone for the treatment of many malignancies. Nephrotoxicity is the primary
      dose-limiting toxicity, and various hydration regimens and supplementation
      strategies are used to prevent cisplatin-induced kidney injury. However, evidence
      based recommendations on specific hydration regimens are limited. A systematic
      review was performed to evaluate clinical studies that have examined hydration
      and supplementation strategies to prevent cisplatin-induced nephrotoxicity.
      MATERIALS AND METHODS: PubMed and Excerpta Medica databases were searched from
      1966 through October 2015 for clinical trials and other studies focused on
      hydration regimens to prevent nephrotoxicity in cancer patients treated with
      cisplatin. The University of Oxford Centre for Evidence-Based Medicine criteria
      were used to grade level of evidence. RESULTS: Among the 1,407 identified
      studies, 24 were included in this systematic review. All studies differed on
      type, volume, and duration of hydration. Among the 24 studies, 5 evaluated short
      duration hydration, 4 evaluated low-volume hydration, 4 investigated magnesium
      supplementation, and 7 reviewed forced diuresis with hydration. Short-duration
      and lower-volume hydration regimens are effective in preventing cisplatin-induced
      nephrotoxicity. Magnesium supplementation may have a role as a nephroprotectant,
      and forced diuresis may be appropriate in some patients receiving cisplatin.
      CONCLUSION: Hydration is essential for all patients to prevent cisplatin-induced
      nephrotoxicity. Specifically, short-duration, low-volume, outpatient hydration
      with magnesium supplementation and mannitol forced diuresis (in select patients)
      represent best practice principles for the safe use of cisplatin. The Oncologist
      2017;22:609-619 IMPLICATIONS FOR PRACTICE: The findings contained within this
      systematic review show that (a) hydration is essential for all patients to
      prevent cisplatin-induced nephrotoxicity, (b) short-duration, low-volume,
      outpatient hydration regimens appear to be safe and feasible, even in patients
      receiving intermediate- to high-dose cisplatin, (c) magnesium supplementation (8
      16 milliequivalents) may limit cisplatin-induced nephrotoxicity, and (d) mannitol
      may be considered for high-dose cisplatin and/or patients with preexisting
      hypertension. These findings have broad implications for clinical practice and
      represent best practice principles for the prevention of cisplatin-induced
      nephrotoxicity.

PMID- 28438888
TI  - Accessibility, Availability, and Potential Benefits of Psycho-Oncology Services:
      The Perspective of Community-Based Physicians Providing Cancer Survivorship Care.
AB  - BACKGROUND: As persons of trust, community-based physicians providing
      survivorship care (e.g., general practitioners [GPs]) often serve as the primary
      contacts for cancer survivors disclosing distress. From the perspective of
      physicians providing survivorship care for cancer patients, this study explores
      (a) the accessibility, availability, and potential benefits of psycho-oncology
      services; (b) whether physicians themselves provide psychosocial support; and (c)
      predictors for impeded referrals of survivors to services. METHODS: In a cross
      sectional survey, all GPs and community-based specialists in a defined region
      were interviewed. In addition to descriptive analyses, categorical data were
      investigated by applying chi-square tests. Predictors for impeded referrals were
      explored through logistic regression. RESULTS: Of 683 responding physicians, the
      vast majority stated that survivors benefit from psycho-oncology services
      (96.8%), but the physicians also articulated that insufficient coverage of psycho
      oncology services (90.9%) was often accompanied by impeded referrals (77.7%). A
      substantial proportion (14.9%) of physicians did not offer any psychosocial
      support. The odds of physicians in rural areas reporting impeded referrals were
      1.91 times greater than the odds of physicians in large urban areas making a
      similar report (95% confidence interval [1.07, 3.40]). CONCLUSION: Most community
      based physicians providing survivorship care regard psycho-oncology services as
      highly beneficial. However, a large number of physicians report tremendous
      difficulty referring patients. Focusing on those physicians not providing any
      psychosocial support, health policy approaches should specifically (a) raise
      awareness of the role of physicians as persons of trust for survivors, (b)
      highlight the effectiveness of psycho-oncology services, and (c) encourage a
      proactive attitude toward the assessment of unmet needs and the initiation of
      comprehensive care. IMPLICATIONS FOR PRACTICE: Community-based physicians
      providing survivorship care for cancer patients regard psycho-oncology services
      as a highly reasonable and beneficial addition to medical care. In light of
      insufficient local coverage with services, difficulties with seamless referrals
      constitute a major challenge for physicians. Apart from emphasizing the
      effectiveness of psycho-oncology services and proactive attitudes toward the
      assessment of unmet needs, future policies should focus on the integration of
      medical and psychosocial follow-up of cancer survivors, especially in rural
      areas.

PMID- 28438889
TI  - FDA Approval Summary: Nivolumab for the Treatment of Relapsed or Progressive
      Classical Hodgkin Lymphoma.
AB  - On May 17, 2016, after an expedited priority review, the U.S. Food and Drug
      Administration granted accelerated approval to nivolumab for the treatment of
      patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed
      after autologous hematopoietic stem cell transplantation (HSCT) and post
      transplantation brentuximab vedotin (BV). Nivolumab in cHL had been granted
      breakthrough therapy designation. Accelerated approval was based on two single
      arm, multicenter trials in adults with cHL. In 95 patients with relapsed or
      progressive cHL after autologous HSCT and post-transplantation BV, nivolumab,
      dosed at 3 mg/kg intravenously every 2 weeks, produced a 65% (95% confidence
      interval: 55%-75%) objective response rate (58% partial remission, 7% complete
      remission). The estimated median duration of response was 8.7 months, with 4.6
      month median follow-up for response duration. The median time to response was 2.1
      (range: 0.7-5.7) months. Among 263 patients with cHL treated with nivolumab, 21%
      reported serious adverse reactions (ARs). The most common all-grade ARs (reported
      in >=20%) were fatigue, upper respiratory tract infection, cough, pyrexia,
      diarrhea, elevated transaminases, and cytopenias. Infusion-related reaction and
      hypothyroidism or thyroiditis occurred in >10% of patients; other immune-mediated
      ARs, occurring in 1%-5%, included rash, pneumonitis, hepatitis, hyperthyroidism,
      and colitis. A new Warning and Precaution was issued for complications of
      allogeneic HSCT after nivolumab, including severe or hyperacute graft-versus-host
      disease, other immune-mediated ARs, and transplant-related mortality. Continued
      approval for the cHL indication may be contingent upon verification of clinical
      benefit in a randomized trial. The Oncologist 2017;22:585-591 IMPLICATIONS FOR
      PRACTICE: Based on response rate and duration in single-arm studies, nivolumab is
      a new treatment option for patients with classical Hodgkin lymphoma (cHL) that
      has relapsed or progressed despite autologous hematopoietic stem cell
      transplantation (HSCT) and brentuximab vedotin. This was the first U.S. Food and
      Drug Administration marketing application for a programmed cell death 1 inhibitor
      in hematologic malignancies. The use of immune checkpoint blockade in cHL
      represents a new treatment paradigm. The safety of allogeneic HSCT after
      nivolumab requires further evaluation, as does the safety of nivolumab after
      allogeneic HSCT.

PMID- 28438890
TI  - Short FtsZ filaments can drive asymmetric cell envelope constriction at the onset
      of bacterial cytokinesis.
AB  - FtsZ, the bacterial homologue of eukaryotic tubulin, plays a central role in cell
      division in nearly all bacteria and many archaea. It forms filaments under the
      cytoplasmic membrane at the division site where, together with other proteins it
      recruits, it drives peptidoglycan synthesis and constricts the cell. Despite
      extensive study, the arrangement of FtsZ filaments and their role in division
      continue to be debated. Here, we apply electron cryotomography to image the
      native structure of intact dividing cells and show that constriction in a variety
      of Gram-negative bacterial cells, including Proteus mirabilis and Caulobacter
      crescentus, initiates asymmetrically, accompanied by asymmetric peptidoglycan
      incorporation and short FtsZ-like filament formation. These results show that a
      complete ring of FtsZ is not required for constriction and lead us to propose a
      model for FtsZ-driven division in which short dynamic FtsZ filaments can drive
      initial peptidoglycan synthesis and envelope constriction at the onset of
      cytokinesis, later increasing in length and number to encircle the division plane
      and complete constriction.

PMID- 28438891
TI  - A second Wpl1 anti-cohesion pathway requires dephosphorylation of fission yeast
      kleisin Rad21 by PP4.
AB  - Cohesin mediates sister chromatid cohesion which is essential for chromosome
      segregation and repair. Sister chromatid cohesion requires an acetyl-transferase
      (Eso1 in fission yeast) counteracting Wpl1, promoting cohesin release from DNA We
      report here that Wpl1 anti-cohesion function includes an additional mechanism. A
      genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell
      survival in the complete absence of Eso1. PP4 co-immunoprecipitated Wpl1 and
      cohesin and Wpl1 triggered Rad21 de-phosphorylation in a PP4-dependent manner.
      Relevant residues were identified and mapped within the central domain of Rad21.
      Phospho-mimicking alleles dampened Wpl1 anti-cohesion activity, while alanine
      mutants were neutral indicating that Rad21 phosphorylation would shelter cohesin
      from Wpl1 unless erased by PP4. Experiments in post-replicative cells lacking
      Eso1 revealed two cohesin populations. Type 1 was released from DNA by Wpl1 in a
      PP4-independent manner. Type 2 cohesin, however, remained DNA-bound and lost its
      cohesiveness in a manner depending on Wpl1- and PP4-mediated Rad21 de
      phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid
      cohesion by a novel pathway regulated by the phosphorylation status of the
      cohesin kleisin subunit.

PMID- 28438893
TI  - Revealing the inner workings of organoids.

PMID- 28438894
TI  - Flow diverter treatment of intracranial vertebral artery dissecting
      pseudoaneurysms.
AB  - INTRODUCTION: Intracranial vertebral dissecting pseudoaneurysms are a rare, but
      increasingly recognized, cause of subarachnoid hemorrhage and ischemic stroke.
      The risks of aneurysm re-rupture and associated morbidity are high. The use of
      flow diverter stents for the treatment of these aneurysms has not been well
      studied. OBJECTIVE: To report our data and provide a summarized review of
      literature using flow diverter stents for the treatment of intracranial vertebral
      artery dissecting pseudoaneurysms. METHODS: We performed a retrospective analysis
      of flow diverter stents used for the treatment of intracranial vertebral artery
      dissecting pseudoaneurysms. Clinical, imaging, procedural, and follow-up data
      were collected. RESULTS: We identified eight vertebral dissecting pseudoaneurysms
      in seven patients (5 (71.4%) female; median age 47 years (IQR 46-52)) who had
      undergone treatment with flow diverter stents. In 4/7 patients (57.1%) the
      aneurysm had ruptured; however, only one was treated in the acute phase. Median
      size of the largest diameter of the aneurysm was 6.3 mm (IQR 4.2-8.8), and 7/8
      aneurysms (87.5%) were treated with a single flow diverter device. Three
      aneurysms were concurrently coiled. Angiographic complete occlusion was seen in
      6/8 (75%) aneurysms at a median follow-up of 14 months (IQR 7.7-20.2). Two
      patients had periprocedural strokes with transient neurologic deficits. All
      patients had a good clinical outcome (modified Rankin Scale score <=2). There
      were no re-treatments or aneurysm ruptures during the follow-up period.
      CONCLUSIONS: Our experience suggests that flow diverter stent treatment of
      intracranial vertebral artery dissecting pseudoaneurysms is safe, and associated
      with good occlusion rates and favorable clinical outcomes.

PMID- 28438895
TI  - The Casper carotid artery stent: a unique all metal micromesh stent designed to
      prevent embolic release.
AB  - BACKGROUND: Stroke due to the release of embolic debris during the placement of a
      stent to correct carotid artery stenosis is a constant procedural and peri
      procedural threat. The new all metal Casper stent has been created with two
      layers of nitinol, the inner layer of which has pores diminutive enough to
      prevent embolic release. OBJECTIVE: To evaluate the safety, effectiveness, and
      utility of the double layer nitinol Casper carotid artery stent in the treatment
      of patients with severe carotid artery stenosis. METHODS: 19 patients with severe
      internal carotid artery stenosis, 14 symptomatic and 5 asymptomatic, were treated
      with the Casper stent. After stent placement, angiographic and cone beam CT
      images were recorded in all patients. RESULTS: The unique low profile delivery
      system allowed for easy stent placement, re-sheathing, and repositioning of the
      stent. The large cell external layer produced excellent apposition to the artery
      wall. The inner layer prevented prolapse of atherosclerotic debris through the
      device. Plaque coverage was achieved; residual stenosis ranged from 0% to 20%.
      Long term angiographic follow-up in 5 patients showed wall apposition of the
      device covering the lesion and no restenosis. There were no procedure related
      complications. Two patients experienced a delayed ischemic stroke, likely related
      to inconsistent medical management. CONCLUSIONS: The Casper has been an excellent
      stent for the treatment of internal carotid artery stenosis and its internal
      micromesh layer has been effective in preventing plaque prolapse. It provides the
      flexibility of large cell stents and the inner layer provides maximum protection
      against plaque prolapse.

PMID- 28438892
TI  - Brain metabolism in health, aging, and neurodegeneration.
AB  - Brain cells normally respond adaptively to bioenergetic challenges resulting from
      ongoing activity in neuronal circuits, and from environmental energetic stressors
      such as food deprivation and physical exertion. At the cellular level, such
      adaptive responses include the "strengthening" of existing synapses, the
      formation of new synapses, and the production of new neurons from stem cells. At
      the molecular level, bioenergetic challenges result in the activation of
      transcription factors that induce the expression of proteins that bolster the
      resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and
      proteotoxic stresses involved in the pathogenesis of brain disorders including
      stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that
      lifestyles that include intermittent bioenergetic challenges, most notably
      exercise and dietary energy restriction, can increase the likelihood that the
      brain will function optimally and in the absence of disease throughout life.
      Here, we provide an overview of cellular and molecular mechanisms that regulate
      brain energy metabolism, how such mechanisms are altered during aging and in
      neurodegenerative disorders, and the potential applications to brain health and
      disease of interventions that engage pathways involved in neuronal adaptations to
      metabolic stress.

PMID- 28438896
TI  - Mechanisms That Shape Human Antibody Repertoire Development in Mice Transgenic
      for Human Ig H and L Chain Loci.
AB  - To determine the impact of the milieu on the development of the human B cell
      repertoire, we carried out a comprehensive analysis of productive and
      nonproductive Ig gene rearrangements from transgenic mice engineered to express
      single copies of the unrearranged human H chain and L chain Ig gene loci. By
      examining the nonproductive repertoire as an indication of the immediate product
      of the rearrangement machinery without an impact of selection, we discovered that
      the distribution of human rearrangements arising in the mouse was generally
      comparable to that seen in humans. However, differences between the distribution
      of nonproductive and productive rearrangements that reflect the impact of
      selection suggested species-specific selection played a role in shaping the
      respective repertoires. Although expression of some VH genes was similar in mouse
      and human (IGHV3-23, IGHV3-30, and IGHV4-59), other genes behaved differently
      (IGHV3-33, IGHV3-48, IGHV4-31, IGHV4-34, and IGHV1-18). Gene selection
      differences were also noted in L chains. Notably, nonproductive human VH
      rearrangements in the transgenic mice expressed shorter CDRH3 with less N
      addition. Even the CDRH3s in the productive rearrangements were shorter in length
      than those of the normal human productive repertoire. Amino acids in the CDRH3s
      in both species showed positive selection of tyrosines and glycines, and negative
      selection of leucines. The data indicate that the environment in which B cells
      develop can affect the expressed Ig repertoire by exerting influences on the
      distribution of expressed VH and VL genes and by influencing the amino acid
      composition of the Ag binding site.

PMID- 28438897
TI  - Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the
      Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells.
AB  - Systemic lupus erythematosus (SLE) damages multiple organs by producing various
      autoantibodies. In this study, we report that decreased microRNA (miR)-200a-3p
      causes IL-2 hypoproduction through zinc finger E-box binding homeobox (ZEB)1 and
      C-terminal binding protein 2 (CtBP2) in a lupus-prone mouse. First, we performed
      RNA sequencing to identify candidate microRNAs and mRNAs involved in the
      pathogenesis of SLE. We found that miR-200a-3p was significantly downregulated,
      whereas its putative targets, ZEB2 and CtBP2, were upregulated in CD4+ T cells
      from MRL/lpr-Tnfrsf6lpr mice compared with C57BL/6J mice. ZEB1 and ZEB2 comprise
      the ZEB family and suppress various genes, including IL-2 by recruiting CtBP2. IL
      2 plays a critical role in immune tolerance, and insufficient IL-2 production
      upon stimulation has been recognized in SLE pathogenesis. Therefore, we
      hypothesized that decreased miR-200a-3p causes IL-2 deficit through the ZEB1
      CtBP2 and/or ZEB2-CtBP2 complex in SLE CD4+ T cells. Overexpression of miR-200a
      3p induced IL-2 production by downregulating ZEB1, ZEB2, and CtBP2 in EL4 cell
      lines. We further revealed that miR-200a-3p promotes IL-2 expression by reducing
      the binding of suppressive ZEB1-CtBP2 and ZEB2-CtBP2 complexes on negative
      regulatory element A in the IL-2 promoter in EL4 cells. Interestingly, the ZEB1
      CtBP2 complex on negative regulatory element A was significantly upregulated
      after PMA/ionomycin stimulation in lupus CD4+ T cells. Our studies have revealed
      a new epigenetic pathway in the control of IL-2 production in SLE whereby low
      levels of miR-200a-3p accumulate the binding of the ZEB1-CtBP2 complex to the IL
      2 promoter and suppress IL-2 production.

PMID- 28438898
TI  - Cytotoxic T Cell Functions Accumulate When CD4 Is Downregulated by CD4+ T Cells
      in African Green Monkeys.
AB  - African green monkeys (AGMs) are a natural host of SIV that do not develop simian
      AIDS. Adult AGMs naturally have low numbers of CD4+ T cells and a large
      population of MHC class II-restricted CD8alphaalpha T cells that are generated
      through CD4 downregulation in CD4+ T cells. In this article, we study the
      functional profiles and SIV infection status in vivo of CD4+ T cells,
      CD8alphaalpha T cells, and CD8alphabeta T cells in lymph nodes, peripheral blood,
      and bronchoalveolar lavage fluid of AGMs and rhesus macaques (in which CD4
      downregulation is not observed). We show that, although CD8alphaalpha T cells in
      AGMs maintain functions associated with CD4+ T cells (including Th follicular
      functionality in lymphoid tissues and Th2 responses in bronchoalveolar lavage
      fluid), they also accumulate functions normally attributed to canonical CD8+ T
      cells. These hyperfunctional CD8alphaalpha T cells are found to circulate
      peripherally, as well as reside within the lymphoid tissue. Due to their unique
      combination of CD4 and CD8 T cell effector functions, these CD4- CD8alphaalpha T
      cells are likely able to serve as an immunophenotype capable of Th1, follicular
      Th, and CTL functionalities, yet they are unable to be infected by SIV. These
      data demonstrate the ambiguity of CD4/CD8 expression in dictating the functional
      capacities of T cells and suggest that accumulation of hyperfunctional
      CD8alphaalpha T cells in AGMs may lead to tissue-specific antiviral immune
      responses in lymphoid follicles that limit SIV replication in this particular
      anatomical niche.

PMID- 28438899
TI  - Galectin-3: A Positive Regulator of Leukocyte Recruitment in the Inflamed
      Microcirculation.
AB  - In vivo and ex vivo imaging were used to investigate the function of galectin-3
      (Gal-3) during the process of leukocyte recruitment to the inflamed
      microcirculation. The cremasteric microcirculation of wild-type (C57BL/6), Gal-3
      /-, and CX3CR1gfp/+ mice were assessed by intravital microscopy after PBS, IL
      1beta, TNF-alpha, or recombinant Gal-3 treatment. These cellular responses were
      investigated further using flow-chamber assays, confocal microscopy, flow
      cytometry, PCR analysis, and proteome array. We show that mechanisms mediating
      leukocyte slow rolling and emigration are impaired in Gal-3-/- mice, which could
      be because of impaired expression of cell adhesion molecules and an altered cell
      surface glycoproteome. Local (intrascrotal) administration of recombinant Gal-3
      to wild-type mice resulted in a dose-dependent reduction in rolling velocity
      associated with increased numbers of adherent and emigrated leukocytes, ~50% of
      which were Ly6G+ neutrophils. Intrascrotal administration of Gal-3 to CX3CR1gfp/+
      mice confirmed that approximately equal numbers of monocytes are also recruited
      in response to this lectin. Exogenous Gal-3 treatment was accompanied by
      increased proinflammatory cytokines and chemokines within the local tissue. In
      conclusion, this study unveils novel biology for both exogenous and endogenous
      Gal-3 in promoting leukocyte recruitment during acute inflammation.

PMID- 28438900
TI  - Definition of the Nature and Hapten Threshold of the beta-Lactam Antigen Required
      for T Cell Activation In Vitro and in Patients.
AB  - Covalent modification of protein by drugs may disrupt self-tolerance, leading to
      lymphocyte activation. Until now, determination of the threshold required for
      this process has not been possible. Therefore, we performed quantitative mass
      spectrometric analyses to define the epitopes formed in tolerant and
      hypersensitive patients taking the beta-lactam antibiotic piperacillin and the
      threshold required for T cell activation. A hydrolyzed piperacillin hapten was
      detected on four lysine residues of human serum albumin (HSA) isolated from
      tolerant patients. The level of modified Lys541 ranged from 2.6 to 4.8%. Analysis
      of plasma from hypersensitive patients revealed the same pattern and levels of
      modification 1-10 d after the commencement of therapy. Piperacillin-responsive
      skin-homing CD4+ clones expressing an array of Vbeta receptors were activated in
      a dose-, time-, and processing-dependent manner; analysis of incubation medium
      revealed that 2.6% of Lys541 in HSA was modified when T cells were activated.
      Piperacillin-HSA conjugates that had levels and epitopes identical to those
      detected in patients were shown to selectively stimulate additional CD4+ clones,
      which expressed a more restricted Vbeta repertoire. To conclude, the levels of
      piperacillin-HSA modification that activated T cells are equivalent to the ones
      formed in hypersensitive and tolerant patients, which indicates that threshold
      levels of drug Ag are formed in all patients. Thus, the propensity to develop
      hypersensitivity is dependent on other factors, such as the presence of T cells
      within an individual's repertoire that can be activated with the beta-lactam
      hapten and/or an imbalance in immune regulation.

PMID- 28438901
TI  - Systolic Blood Pressure and Vascular Disease in Men Aged 65 Years and Over: The
      HIMS (Health in Men Study).
AB  - There is uncertainty about the relation between blood pressure and vascular
      disease at older age. We assessed the association of systolic blood pressure
      (SBP) and major vascular events in a prospective cohort study of 7564 men aged 65
      to 94 years, recruited in 1996-1999 from the general population in Perth, Western
      Australia. SBP was measured at baseline and again at resurvey in 2001-2004.
      Participants were monitored for fatal and nonfatal vascular events. To limit the
      effect of reverse causality, analyses were restricted to men without previous
      vascular disease at baseline. Hazard ratios were estimated by Cox regression,
      with adjustment for age and education (further adjustment did not materially
      change the associations). During a mean follow-up of 11 years, there were 1557
      major vascular events. Continuous log-linear associations were found between
      usual SBP and risk of major vascular events throughout the SBP range examined
      (145-170 mm Hg). Overall, 10 mm Hg higher usual SBP was associated with ~20%
      higher risk of major vascular events (hazard ratio, 19%; 95% confidence interval,
      13%-26%; mean age at event 80 years). There was evidence of positive associations
      with both ischemic heart disease and stroke and effect modification by age, with
      shallower associations at older ages. Even at 85 to 94 years, however, there was
      evidence of a positive association: 10 mm Hg higher usual SBP was associated with
      14% (95% confidence interval, 1%-30%) higher risk of major vascular events.

PMID- 28438903
TI  - Accuracy of Automated Blood Pressure Measurement in Children: Evidence, Issues,
      and Perspectives.

PMID- 28438902
TI  - Crucial Role of ROCK2-Mediated Phosphorylation and Upregulation of FHOD3 in the
      Pathogenesis of Angiotensin II-Induced Cardiac Hypertrophy.
AB  - Cardiac hypertrophy is characterized by increased myofibrillogenesis. Angiotensin
      II (Ang-II) is an essential mediator of the pressure overload-induced cardiac
      hypertrophy in part through RhoA/ROCK (small GTPase/Rho-associated coiled-coil
      containing protein kinase) pathway. FHOD3 (formin homology 2 domain containing
      3), a cardiac-restricted member of diaphanous-related formins, is crucial in
      regulating myofibrillogenesis in cardiomyocytes. FHOD3 maintains inactive through
      autoinhibition by an intramolecular interaction between its C- and N-terminal
      domains. Phosphorylation of the 3 highly conserved residues (1406S, 1412S, and
      1416T) within the C terminus (CT) of FHOD3 by ROCK1 is sufficient for its
      activation. However, it is unclear whether ROCK-mediated FHOD3 activation plays a
      role in the pathogenesis of Ang-II-induced cardiac hypertrophy. In this study, we
      detected increases in FHOD3 expression and phosphorylation in cardiomyocytes from
      Ang-II-induced rat cardiac hypertrophy models. Valsartan attenuated such
      increases. In cultured neonate rat cardiomyocytes, overexpression of phosphor
      mimetic mutant FHOD3-DDD, but not wild-type FHOD3, resulted in myofibrillogenesis
      and cardiomyocyte hypertrophy. Expression of a phosphor-resistant mutant FHOD3
      AAA completely abolished myofibrillogenesis and attenuated Ang-II-induced
      cardiomyocyte hypertrophy. Pretreatment of neonate rat cardiomyocytes with ROCK
      inhibitor Y27632 reduced Ang-II-induced FHOD3 activation and upregulation,
      suggesting the involvement of ROCK activities. Silencing of ROCK2, but not ROCK1,
      in neonate rat cardiomyocytes, significantly lessened Ang-II-induced
      cardiomyocyte hypertrophy. ROCK2 can directly phosphorylate FHOD3 at both 1412S
      and 1416T in vitro and is more potent than ROCK1. Both kinases failed to
      phosphorylate 1406S. Coexpression of FHOD3 with constitutively active ROCK2
      induced more stress fiber formation than that with constitutively active ROCK1.
      Collectively, our results demonstrated the importance of ROCK2 regulated FHOD3
      expression and activation in Ang-II-induced myofibrillogenesis, thus provided a
      novel mechanism for the pathogenesis of Ang-II-induced cardiac hypertrophy.

PMID- 28438904
TI  - Loss of Resistance to Angiotensin II-Induced Hypertension in the Jackson
      Laboratory Recombination-Activating Gene Null Mouse on the C57BL/6J Background.
AB  - Resistance to angiotensin II (Ang II)-induced hypertension in T-cell-deficient
      male mice with a targeted mutation in the recombination-activating gene-1 (Rag1)
      on the C57BL/6J background (B6.Rag1-/- -M), which was reported by 5 independent
      laboratories including ours before 2015, has been lost. In mice purchased from
      Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in
      mean arterial pressure induced by 2 weeks of Ang II infusion at 490 ng/kg per
      minute was identical between B6.Rag1-/- -M and male wild-type littermates.
      Moreover, there were no differences in the time course or magnitude increase in
      mean arterial pressure at the lowest dose of Ang II (200 ng/kg per minute) that
      increased mean arterial pressure. This loss in Ang II resistance is independent
      of T cells. Angiotensin type 1-receptor binding was 1.4-fold higher in glomeruli
      isolated from recently purchased B6.Rag1-/- -M suggesting an increase in renal
      angiotensin type 1-receptor activity masks the blood pressure protection afforded
      by the lack of T cells. The phenotypic change in B6.Rag1-/- -M has implications
      for investigators using this strain to study mechanisms of T-cell modulation of
      Ang II-dependent blood pressure control. These findings also serve as a reminder
      that the universal drive for genetic variation occurs in all animals including
      inbred mouse strains and that spontaneous mutations leading to phenotypic change
      can compromise experimental reproducibility over time and place. Finally, these
      observations illustrate the importance of including experimental details about
      the location and time period over which animals are bred in publications
      involving animal studies to promote rigor and reproducibility in the scientific
      literature.

PMID- 28438905
TI  - Brachial-Ankle Pulse Wave Velocity and the Risk Prediction of Cardiovascular
      Disease: An Individual Participant Data Meta-Analysis.
AB  - An individual participant data meta-analysis was conducted in the data of 14 673
      Japanese participants without a history of cardiovascular disease (CVD) to
      examine the association of the brachial-ankle pulse wave velocity (baPWV) with
      the risk of development of CVD. During the average 6.4-year follow-up period, 687
      participants died and 735 developed cardiovascular events. A higher baPWV was
      significantly associated with a higher risk of CVD, even after adjustments for
      conventional risk factors (P for trend <0.001). When the baPWV values were
      classified into quintiles, the multivariable-adjusted hazard ratio for CVD
      increased significantly as the baPWV quintile increased. The hazard ratio in the
      subjects with baPWV values in quintile 5 versus that in those with the values in
      quintile 1 was 3.50 (2.14-5.74; P<0.001). Every 1 SD increase of the baPWV was
      associated with a 1.19-fold (1.10-1.29; P<0.001) increase in the risk of CVD.
      Moreover, addition of baPWV to a model incorporating the Framingham risk score
      significantly increased the C statistics from 0.8026 to 0.8131 (P<0.001) and also
      improved the category-free net reclassification (0.247; P<0.001). The present
      meta-analysis clearly established baPWV as an independent predictor of the risk
      of development of CVD in Japanese subjects without preexisting CVD. Thus,
      measurement of the baPWV could enhance the efficacy of prediction of the risk of
      development of CVD over that of the Framingham risk score, which is based on the
      traditional cardiovascular risk factors.

PMID- 28438906
TI  - Novel Screening Tool for Stroke Using Artificial Neural Network.
AB  - BACKGROUND AND PURPOSE: The timely diagnosis of stroke at the initial examination
      is extremely important given the disease morbidity and narrow time window for
      intervention. The goal of this study was to develop a supervised learning method
      to recognize acute cerebral ischemia (ACI) and differentiate that from stroke
      mimics in an emergency setting. METHODS: Consecutive patients presenting to the
      emergency department with stroke-like symptoms, within 4.5 hours of symptoms
      onset, in 2 tertiary care stroke centers were randomized for inclusion in the
      model. We developed an artificial neural network (ANN) model. The learning
      algorithm was based on backpropagation. To validate the model, we used a 10-fold
      cross-validation method. RESULTS: A total of 260 patients (equal number of stroke
      mimics and ACIs) were enrolled for the development and validation of our ANN
      model. Our analysis indicated that the average sensitivity and specificity of ANN
      for the diagnosis of ACI based on the 10-fold cross-validation analysis was 80.0%
      (95% confidence interval, 71.8-86.3) and 86.2% (95% confidence interval, 78.7
      91.4), respectively. The median precision of ANN for the diagnosis of ACI was 92%
      (95% confidence interval, 88.7-95.3). CONCLUSIONS: Our results show that ANN can
      be an effective tool for the recognition of ACI and differentiation of ACI from
      stroke mimics at the initial examination.

PMID- 28438907
TI  - "Good Outcome" Isn't Good Enough: Cognitive Impairment, Depressive Symptoms, and
      Social Restrictions in Physically Recovered Stroke Patients.
AB  - BACKGROUND AND PURPOSE: Functional outcome after stroke is often only evaluated
      using the modified Rankin Scale, which primarily assesses activities of daily
      living. Stroke patients may experience difficulties with social reintegration and
      mental functions, feel isolated, and experience poor quality of life, even after
      physical recovery is complete. Functional assessments based solely on activity
      limitations may not be able to capture the full range of problems experienced by
      stroke survivors. METHODS: Telephone interviews were conducted 2 to 3 years
      poststroke to assess outcome on multiple levels of functioning as stated in the
      WHO International Classification of Functioning: body function (Montreal
      Cognitive Assessment and Patient Health Questionnaire-2), activity (modified
      Rankin Scale), and participation (Reintegration to Normal Living Index). RESULTS:
      Ninety-six (68%) patients had a favorable functional outcome (modified Rankin
      Scale <2). Of these, 79, 91, and 93 patients completed the Montreal Cognitive
      Assessment, Reintegration to Normal Living Index, and Patient Health
      Questionnaire-2, respectively. Forty-three (54%) patients were cognitively
      impaired, 47 (52%) had restrictions in reintegration, and 30 (32%) endorsed
      symptoms of depression. There was no difference in Montreal Cognitive Assessment
      or Patient Health Questionnaire-2 scores between those who had activity
      limitations and those who had not. CONCLUSIONS: More than half of stroke patients
      with excellent functional recovery measured by the modified Rankin Scale continue
      to have cognitive impairment and participation restrictions, and one third of
      patients continue to have depression 2 to 3 years later. Current definitions of
      good functional outcome used in the majority of stroke acute trials focus on
      activity limitations, but greater attention to multiple levels of recovery is
      required.

PMID- 28438908
TI  - Comparison of Associations of Reduced Estimated Glomerular Filtration Rate With
      Stroke Outcomes Between Hypertension and No Hypertension.
AB  - BACKGROUND AND PURPOSE: We compared the association of low estimated glomerular
      filtration rate (eGFR) with stroke outcomes among patients with hypertension and
      without hypertension. METHODS: We used the China stroke registry to identify
      patients on discharge with the diagnosis of stroke in 2012 and 2013. Low eGFR was
      defined as <60 mL/min/1.73 m2. Multivariable analysis was used to evaluate the
      association of low eGFR with 1-year all-cause mortality, recurrent stroke, poor
      functional outcome defined as 3 to 6 in modified Rankin Scale (mRS), and ordinal
      mRS, where the interaction of eGFR category and hypertension status was
      investigated. RESULTS: Of 5082 patients without hypertension, 221 patients (4.4%)
      had low eGFR, as compared with 1378 patients (8.6%) previously diagnosed with
      hypertension. In patients without hypertension, the adjusted odds ratios with 95%
      confidence interval of low eGFR was 1.88 (1.23-2.88) for all-cause mortality,
      1.36 (0.66-2.83) for recurrent stroke, 2.14 (1.45-3.16) for poor functional
      outcome, and 2.07 (1.58-2.70) for ordinal mRS. In patients with hypertension, low
      eGFR was associated with all stroke outcomes: 1.80 (1.50-2.16) for all-cause
      mortality, 1.52 (1.20-1.91) for recurrent stroke, 1.30 (1.11-1.52) for poor
      functional outcome, and 1.31 (1.18-1.46) for ordinal mRS. The significant
      interaction between eGFR categories and hypertension was only found for poor
      functional outcome (P=0.046) and ordinal mRS (P=0.002). CONCLUSIONS: Effect of
      low eGFR on all-cause mortality and recurrent stroke in patients without
      hypertension was not significantly different from that in patients with
      hypertension, but low-eGFR patients without hypertension had a higher risk of
      stroke-related disability than those with hypertension.

PMID- 28438909
TI  - Interacting effects of land use and climate on rodent-borne pathogens in central
      Kenya.
AB  - Understanding the effects of anthropogenic disturbance on zoonotic disease risk
      is both a critical conservation objective and a public health priority. Here, we
      evaluate the effects of multiple forms of anthropogenic disturbance across a
      precipitation gradient on the abundance of pathogen-infected small mammal hosts
      in a multi-host, multi-pathogen system in central Kenya. Our results suggest that
      conversion to cropland and wildlife loss alone drive systematic increases in
      rodent-borne pathogen prevalence, but that pastoral conversion has no such
      systematic effects. The effects are most likely explained both by changes in
      total small mammal abundance, and by changes in relative abundance of a few high
      competence species, although changes in vector assemblages may also be involved.
      Several pathogens responded to interactions between disturbance type and climatic
      conditions, suggesting the potential for synergistic effects of anthropogenic
      disturbance and climate change on the distribution of disease risk. Overall,
      these results indicate that conservation can be an effective tool for reducing
      abundance of rodent-borne pathogens in some contexts (e.g. wildlife loss alone);
      however, given the strong variation in effects across disturbance types, pathogen
      taxa and environmental conditions, the use of conservation as public health
      interventions will need to be carefully tailored to specific pathogens and human
      contexts.This article is part of the themed issue 'Conservation, biodiversity and
      infectious disease: scientific evidence and policy implications'.

PMID- 28438911
TI  - Human infectious disease burdens decrease with urbanization but not with
      biodiversity.
AB  - Infectious disease burdens vary from country to country and year to year due to
      ecological and economic drivers. Recently, Murray et al. (Murray CJ et al 2012
      Lancet380, 2197-2223. (doi:10.1016/S0140-6736(12)61689-4)) estimated country
      level morbidity and mortality associated with a variety of factors, including
      infectious diseases, for the years 1990 and 2010. Unlike other databases that
      report disease prevalence or count outbreaks per country, Murray et al. report
      health impacts in per-person disability-adjusted life years (DALYs), allowing
      comparison across diseases with lethal and sublethal health effects. We
      investigated the spatial and temporal relationships between DALYs lost to
      infectious disease and potential demographic, economic, environmental and biotic
      drivers, for the 60 intermediate-sized countries where data were available and
      comparable. Most drivers had unique associations with each disease. For example,
      temperature was positively associated with some diseases and negatively
      associated with others, perhaps due to differences in disease agent thermal
      optima, transmission modes and host species identities. Biodiverse countries
      tended to have high disease burdens, consistent with the expectation that high
      diversity of potential hosts should support high disease transmission. Contrary
      to the dilution effect hypothesis, increases in biodiversity over time were not
      correlated with improvements in human health, and increases in forestation over
      time were actually associated with increased disease burden. Urbanization and
      wealth were associated with lower burdens for many diseases, a pattern that could
      arise from increased access to sanitation and healthcare in cities and increased
      investment in healthcare. The importance of urbanization and wealth helps to
      explain why most infectious diseases have become less burdensome over the past
      three decades, and points to possible levers for further progress in improving
      global public health.This article is part of the themed issue 'Conservation,
      biodiversity and infectious disease: scientific evidence and policy
      implications'.

PMID- 28438910
TI  - Lyme disease ecology in a changing world: consensus, uncertainty and critical
      gaps for improving control.
AB  - Lyme disease is the most common tick-borne disease in temperate regions of North
      America, Europe and Asia, and the number of reported cases has increased in many
      regions as landscapes have been altered. Although there has been extensive work
      on the ecology and epidemiology of this disease in both Europe and North America,
      substantial uncertainty exists about fundamental aspects that determine spatial
      and temporal variation in both disease risk and human incidence, which hamper
      effective and efficient prevention and control. Here we describe areas of
      consensus that can be built on, identify areas of uncertainty and outline
      research needed to fill these gaps to facilitate predictive models of disease
      risk and the development of novel disease control strategies. Key areas of
      uncertainty include: (i) the precise influence of deer abundance on tick
      abundance, (ii) how tick populations are regulated, (iii) assembly of host
      communities and tick-feeding patterns across different habitats, (iv) reservoir
      competence of host species, and (v) pathogenicity for humans of different
      genotypes of Borrelia burgdorferi Filling these knowledge gaps will improve Lyme
      disease prevention and control and provide general insights into the drivers and
      dynamics of this emblematic multi-host-vector-borne zoonotic disease.This article
      is part of the themed issue 'Conservation, biodiversity and infectious disease:
      scientific evidence and policy implications'.

PMID- 28438912
TI  - Effects of conservation management of landscapes and vertebrate communities on
      Lyme borreliosis risk in the United Kingdom.
AB  - Landscape change and altered host abundance are major drivers of zoonotic
      pathogen emergence. Conservation and biodiversity management of landscapes and
      vertebrate communities can have secondary effects on vector-borne pathogen
      transmission that are important to assess. Here we review the potential
      implications of these activities on the risk of Lyme borreliosis in the United
      Kingdom. Conservation management activities include woodland expansion,
      management and restoration, deer management, urban greening and the release and
      culling of non-native species. Available evidence suggests that increasing
      woodland extent, implementing biodiversity policies that encourage ecotonal
      habitat and urban greening can increase the risk of Lyme borreliosis by
      increasing suitable habitat for hosts and the tick vectors. However, this can
      depend on whether deer population management is carried out as part of these
      conservation activities. Exclusion fencing or culling deer to low densities can
      decrease tick abundance and Lyme borreliosis risk. As management actions often
      constitute large-scale perturbation experiments, these hold great potential to
      understand underlying drivers of tick and pathogen dynamics. We recommend
      integrating monitoring of ticks and the risk of tick-borne pathogens with
      conservation management activities. This would help fill knowledge gaps and the
      production of best practice guidelines to reduce risks.This article is part of
      the themed issue 'Conservation, biodiversity and infectious disease: scientific
      evidence and policy implications'.

PMID- 28438913
TI  - Conservation, biodiversity and infectious disease: scientific evidence and policy
      implications.

PMID- 28438914
TI  - Does deforestation promote or inhibit malaria transmission in the Amazon? A
      systematic literature review and critical appraisal of current evidence.
AB  - Considerable interest in the relationship between biodiversity and disease has
      recently captured the attention of the research community, with important public
      policy implications. In particular, malaria in the Amazon region is often cited
      as an example of how forest conservation can improve public health outcomes.
      However, despite a growing body of literature and an increased understanding of
      the relationship between malaria and land use / land cover change (LULC) in
      Amazonia, contradictions have emerged. While some studies report that
      deforestation increases malaria risk, others claim the opposite. Assessing
      malaria risk requires examination of dynamic processes among three main
      components: (i) the environment (i.e. LULC and landscape transformations), (ii)
      vector biology (e.g. mosquito species distributions, vector activity and life
      cycle, plasmodium infection rates), and (iii) human populations (e.g. forest
      related activity, host susceptibility, movement patterns). In this paper, we
      conduct a systematic literature review on malaria risk and deforestation in the
      Amazon focusing on these three components. We explore key features that are
      likely to generate these contrasting results using the reviewed articles and our
      own data from Brazil and Peru, and conclude with suggestions for productive
      avenues in future research.This article is part of the themed issue
      'Conservation, biodiversity and infectious disease: scientific evidence and
      policy implications'.

PMID- 28438915
TI  - Conservation, development and the management of infectious disease: avian
      influenza in China, 2004-2012.
AB  - There is growing evidence that wildlife conservation measures have mixed effects
      on the emergence and spread of zoonotic disease. Wildlife conservation has been
      found to have both positive (dilution) and negative (contagion) effects. In the
      case of avian influenza H5N1 in China, the focus has been on negative effects.
      Lakes and wetlands attracting migrating waterfowl have been argued to be disease
      hotspots. We consider the implications of waterfowl conservation for H5N1
      infections in both poultry and humans between 2004 and 2012. We model both
      environmental and economic risk factors. Environmental risk factors comprise the
      conditions that structure interaction between wild and domesticated birds.
      Economic risk factors comprise the cost of disease, biosecurity measures and
      disease risk mitigation. We find that H5N1 outbreaks in poultry populations are
      indeed sensitive to the existence of wild-domesticated bird mixing zones, but not
      in the way we would expect from the literature. We find that risk is decreasing
      in protected migratory bird habitat. Since the number of human cases is
      increasing in the number of poultry outbreaks, as expected, the implication is
      that the protection of wetlands important for migratory birds offers unexpected
      human health benefits.This article is part of the themed issue 'Conservation,
      biodiversity and infectious disease: scientific evidence and policy
      implications'.

PMID- 28438916
TI  - Nearly 400 million people are at higher risk of schistosomiasis because dams
      block the migration of snail-eating river prawns.
AB  - Dams have long been associated with elevated burdens of human schistosomiasis,
      but how dams increase disease is not always clear, in part because dams have many
      ecological and socio-economic effects. A recent hypothesis argues that dams block
      reproduction of the migratory river prawns that eat the snail hosts of
      schistosomiasis. In the Senegal River Basin, there is evidence that prawn
      populations declined and schistosomiasis increased after completion of the Diama
      Dam. Restoring prawns to a water-access site upstream of the dam reduced snail
      density and reinfection rates in people. However, whether a similar cascade of
      effects (from dams to prawns to snails to human schistosomiasis) occurs elsewhere
      is unknown. Here, we examine large dams worldwide and identify where their
      catchments intersect with endemic schistosomiasis and the historical habitat
      ranges of large, migratory Macrobrachium spp. prawns. River prawn habitats are
      widespread, and we estimate that 277-385 million people live within
      schistosomiasis-endemic regions where river prawns are or were present (out of
      the 800 million people who are at risk of schistosomiasis). Using a published
      repository of schistosomiasis studies in sub-Saharan Africa, we compared
      infection before and after the construction of 14 large dams for people living
      in: (i) upstream catchments within historical habitats of native prawns, (ii)
      comparable undammed watersheds, and (iii) dammed catchments beyond the historical
      reach of migratory prawns. Damming was followed by greater increases in
      schistosomiasis within prawn habitats than outside prawn habitats. We estimate
      that one third to one half of the global population-at-risk of schistosomiasis
      could benefit from restoration of native prawns. Because dams block prawn
      migrations, our results suggest that prawn extirpation contributes to the sharp
      increase of schistosomiasis after damming, and points to prawn restoration as an
      ecological solution for reducing human disease.This article is part of the themed
      issue 'Conservation, biodiversity and infectious disease: scientific evidence and
      policy implications'.

PMID- 28438917
TI  - Disease ecology, health and the environment: a framework to account for
      ecological and socio-economic drivers in the control of neglected tropical
      diseases.
AB  - Reducing the burden of neglected tropical diseases (NTDs) is one of the key
      strategic targets advanced by the Sustainable Development Goals. Despite the
      unprecedented effort deployed for NTD elimination in the past decade, their
      control, mainly through drug administration, remains particularly challenging:
      persistent poverty and repeated exposure to pathogens embedded in the environment
      limit the efficacy of strategies focused exclusively on human treatment or
      medical care. Here, we present a simple modelling framework to illustrate the
      relative role of ecological and socio-economic drivers of environmentally
      transmitted parasites and pathogens. Through the analysis of system dynamics, we
      show that periodic drug treatments that lead to the elimination of directly
      transmitted diseases may fail to do so in the case of human pathogens with an
      environmental reservoir. Control of environmentally transmitted diseases can be
      more effective when human treatment is complemented with interventions targeting
      the environmental reservoir of the pathogen. We present mechanisms through which
      the environment can influence the dynamics of poverty via disease feedbacks. For
      illustration, we present the case studies of Buruli ulcer and schistosomiasis,
      two devastating waterborne NTDs for which control is particularly
      challenging.This article is part of the themed issue 'Conservation, biodiversity
      and infectious disease: scientific evidence and policy implications'.

PMID- 28438918
TI  - Does the impact of biodiversity differ between emerging and endemic pathogens?
      The need to separate the concepts of hazard and risk.
AB  - Biodiversity is of critical value to human societies, but recent evidence that
      biodiversity may mitigate infectious-disease risk has sparked controversy among
      researchers. The majority of work on this topic has focused on direct assessments
      of the relationship between biodiversity and endemic-pathogen prevalence, without
      disentangling intervening mechanisms; thus study outcomes often differ, fuelling
      more debate. Here, we suggest two critical changes to the approach researchers
      take to understanding relationships between infectious disease, both endemic and
      emerging, and biodiversity that may help clarify sources of controversy. First,
      the distinct concepts of hazards versus risks need to be separated to determine
      how biodiversity and its drivers may act differently on each. This distinction is
      particularly important since it illustrates that disease emergence drivers in
      humans could be quite different to the general relationship between biodiversity
      and transmission of endemic pathogens. Second, the interactive relationship among
      biodiversity, anthropogenic change and zoonotic disease risk, including both
      direct and indirect effects, needs to be recognized and accounted for. By
      carefully disentangling these interactions between humans' activities and
      pathogen circulation in wildlife, we suggest that conservation efforts could
      mitigate disease risks and hazards in novel ways that complement more typical
      disease control efforts.This article is part of the themed issue 'Conservation,
      biodiversity and infectious disease: scientific evidence and policy
      implications'.

PMID- 28438919
TI  - Ecosystem change and human health: implementation economics and policy.
AB  - Several recent initiatives such as Planetary Health, EcoHealth and One Health
      claim that human health depends on flourishing natural ecosystems. However,
      little has been said about the operational and implementation challenges of
      health-oriented conservation actions on the ground. We contend that ecological
      epidemiological research must be complemented by a form of implementation science
      that examines: (i) the links between specific conservation actions and the
      resulting ecological changes, and (ii) how this ecological change impacts human
      health and well-being, when human behaviours are considered. Drawing on the
      policy evaluation tradition in public economics, first, we present three examples
      of recent social science research on conservation interventions that affect human
      health. These examples are from low- and middle-income countries in the tropics
      and subtropics. Second, drawing on these examples, we present three propositions
      related to impact evaluation and non-market valuation that can help guide future
      multidisciplinary research on conservation and human health. Research guided by
      these propositions will allow stakeholders to determine how ecosystem-mediated
      strategies for health promotion compare with more conventional biomedical
      prevention and treatment strategies for safeguarding health.This article is part
      of the themed issue 'Conservation, biodiversity and infectious disease:
      scientific evidence and policy implications'.

PMID- 28438920
TI  - Conservation of biodiversity as a strategy for improving human health and well
      being.
AB  - The Earth's ecosystems have been altered by anthropogenic processes, including
      land use, harvesting populations, species introductions and climate change. These
      anthropogenic processes greatly alter plant and animal communities, thereby
      changing transmission of the zoonotic pathogens they carry. Biodiversity
      conservation may be a potential win-win strategy for maintaining ecosystem health
      and protecting public health, yet the causal evidence to support this strategy is
      limited. Evaluating conservation as a viable public health intervention requires
      answering four questions: (i) Is there a general and causal relationship between
      biodiversity and pathogen transmission, and if so, which direction is it in? (ii)
      Does increased pathogen diversity with increased host biodiversity result in an
      increase in total disease burden? (iii) Do the net benefits of biodiversity
      conservation to human well-being outweigh the benefits that biodiversity
      degrading activities, such as agriculture and resource utilization, provide? (iv)
      Are biodiversity conservation interventions cost-effective when compared to other
      options employed in standard public health approaches? Here, we summarize current
      knowledge on biodiversity-zoonotic disease relationships and outline a research
      plan to address the gaps in our understanding for each of these four questions.
      Developing practical and self-sustaining biodiversity conservation interventions
      will require significant investment in disease ecology research to determine when
      and where they will be effective.This article is part of the themed issue
      'Conservation, biodiversity and infectious disease: scientific evidence and
      policy implications'.

PMID- 28438922
TI  - Surgeons say they expressed safety concerns to hospital bosses before child's
      death.

PMID- 28438921
TI  - Null expectations for disease dynamics in shrinking habitat: dilution or
      amplification?
AB  - As biodiversity declines with anthropogenic land-use change, it is increasingly
      important to understand how changing biodiversity affects infectious disease
      risk. The dilution effect hypothesis, which points to decreases in biodiversity
      as critical to an increase in infection risk, has received considerable attention
      due to the allure of a win-win scenario for conservation and human well-being.
      Yet some empirical data suggest that the dilution effect is not a generalizable
      phenomenon. We explore the response of pathogen transmission dynamics to changes
      in biodiversity that are driven by habitat loss using an allometrically scaled
      multi-host model. With this model, we show that declining habitat, and thus
      declining biodiversity, can lead to either increasing or decreasing infectious
      disease risk, measured as endemic prevalence. Whether larger habitats, and thus
      greater biodiversity, lead to a decrease (dilution effect) or increase
      (amplification effect) in infection prevalence depends upon the pathogen
      transmission mode and how host competence scales with body size. Dilution effects
      were detected for most frequency-transmitted pathogens and amplification effects
      were detected for density-dependent pathogens. Amplification effects were also
      observed over a particular range of habitat loss in frequency-dependent pathogens
      when we assumed that host competence was greatest in large-bodied species. By
      contrast, only amplification effects were observed for density-dependent
      pathogens; host competency only affected the magnitude of the effect. These
      models can be used to guide future empirical studies of biodiversity-disease
      relationships across gradients of habitat loss. The type of transmission, the
      relationship between host competence and community assembly, the identity of
      hosts contributing to transmission, and how transmission scales with area are
      essential factors to consider when elucidating the mechanisms driving disease
      risk in shrinking habitat.This article is part of the themed issue 'Conservation,
      biodiversity and infectious disease: scientific evidence and policy
      implications'.

PMID- 28438923
TI  - Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media.
AB  - Amoxicillin-clavulanate (A/C) is currently the most effective oral antimicrobial
      in treating children with acute otitis media (AOM), but the standard dosage of 90
      mg amoxicillin/6.4 mg clavulanate/kg of body weight/day commonly causes diarrhea.
      We examined whether an A/C formulation containing lower concentrations of
      clavulanate would result in less diarrhea while maintaining plasma levels of
      amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and to
      achieve clinical success. We conducted an open-label study in children with AOM
      who were 6 to 23 months of age. In phase 1, we treated 40 children with a reduced
      clavulanate A/C formulation providing 90 mg amoxicillin/3.2 mg clavulanate/kg/day
      for 10 days. In phase 2, we treated 72 children with the same formulation at a
      dosage of 80 mg amoxicillin/2.85 mg clavulanate/kg/day for 10 days. We compared
      the rates of protocol-defined diarrhea (PDD), diaper dermatitis, and AOM clinical
      response in these children with rates we had reported in children who received
      the standard A/C regimen, and we obtained plasma levels of amoxicillin and
      clavulanate at various time points. Outcomes in phase 1 children and in children
      who had received the standard regimen did not differ significantly. Rates of PDD
      in children receiving phase 2 and standard regimens were 17% and 26%,
      respectively (P = 0.10). The corresponding rates of diaper dermatitis were 21%
      and 33% (P = 0.04) and of AOM treatment failure were 12% and 16% (P = 0.44).
      Symptomatic responses did not differ significantly between regimens; both gave
      clavulanate levels sufficient to inhibit beta-lactamase activity. In young
      children with AOM, clavulanate dosages lower than those currently used may be
      associated with fewer side effects without reducing clinical efficacy. (This
      study has been registered at ClinicalTrials.gov under registration no.
      NCT02630992.).

PMID- 28438924
TI  - Effects on the QT Interval of a Gatifloxacin-Containing Regimen versus Standard
      Treatment of Pulmonary Tuberculosis.
AB  - The effects on ventricular repolarization-recorded on the electrocardiogram (ECG)
      as lengthening of the QT interval-of acute tuberculosis and those of standard and
      alternative antituberculosis regimens are underdocumented. A correction factor
      (QTc) is introduced to make the QT independent of the heart rate, translating
      into the slope of the regression line between QT and heart rate being close to
      zero. ECGs were performed predosing and 1 to 5 h postdosing (month 1, month 2,
      and end of treatment) around drugs' peak concentration time in tuberculosis
      patients treated with either the standard 6-month treatment (rifampin and
      isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; "control")
      or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months
      (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized
      controlled trial conducted in five African countries. Drug levels were measured
      at steady state (month 1) in a subset of patients. We compared treatment effects
      on the QTc and modeled the effect of individual drugs' maximum concentrations of
      drug in serum (Cmax) on the Fridericia-corrected QT interval. A total of 1,686
      patients were eligible for the correction factor analysis of QT at baseline (mean
      age, 30.7 years; 27% female). Median heart rate decreased from 96/min at baseline
      to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5
      degrees C. Pretreatment, the nonlinear model estimated the best correction factor
      at 0.4081 in between Bazett's (0.5) and Fridericia's (0.33) corrections. On
      treatment, Fridericia (QTcF) was the best correction factor. A total of 1,602
      patients contributed to the analysis of QTcF by treatment arm. The peak QTcF
      value during follow-up was >480 ms for 21 patients (7 and 14 in the test and
      control arms, respectively) and >500 ms for 9 patients (5 and 4, respectively),
      corresponding to a risk difference of -0.9% (95% confidence interval [CI], -2.0%
      to 2.3%; P = 0.12) and 0.1% (95% CI, -0.6% to 0.9%; P = 0.75), respectively,
      between the test and control arms. One hundred six (6.6%) patients had a peak
      measurement change from baseline of >60 ms (adjusted between-arm difference,
      0.8%; 95% CI, -1.4% to 3.1%; P = 0.47). No evidence was found of an association
      between Cmax of the antituberculosis drugs 1 month into treatment and the length
      of QTcF. Neither a standard 6-month nor a 4-month gatifloxacin-based regimen
      appears to carry a sizable risk of QT prolongation in patients with newly
      diagnosed pulmonary tuberculosis. This is to date the largest data set studying
      the effects of antituberculosis regimens on the QT, both for the standard regimen
      and for a fluoroquinolone-containing regimen. (This study has been registered at
      ClinicalTrials.gov under identifier NCT00216385.).

PMID- 28438925
TI  - Identification of Mycobacterial Genes Involved in Antibiotic Sensitivity:
      Implications for the Treatment of Tuberculosis with beta-Lactam-Containing
      Regimens.
AB  - In a Mycobacterium smegmatis mutant library screen, transposon mutants with
      insertions in fhaA, dprE2, rpsT, and parA displayed hypersusceptibility to
      antibiotics, including the beta-lactams meropenem, ampicillin, amoxicillin, and
      cefotaxime. Sub-MIC levels of octoclothepin, a psychotic drug inhibiting ParA,
      phenocopied the parA insertion and enhanced the bactericidal activity of
      meropenem against Mycobacterium tuberculosis in combination with clavulanate. Our
      study identifies novel factors associated with antibiotic resistance, with
      implications in repurposing beta-lactams for tuberculosis treatment.

PMID- 28438926
TI  - Evaluation of the Ability of a Novel Miconazole Formulation To Penetrate Nail by
      Using Three In Vitro Nail Models.
AB  - In an effort to increase the efficacy of topical medications for treating
      onychomycosis, several new nail penetration enhancers were recently developed. In
      this study, the ability of 10% (wt/wt) miconazole nitrate combined with a
      penetration enhancer formulation to permeate the nail is demonstrated by the use
      of a selection of in vitro nail penetration assays. These assays included the
      bovine hoof, TurChub zone of inhibition, and infected-nail models.

PMID- 28438927
TI  - Role of psl Genes in Antibiotic Tolerance of Adherent Pseudomonas aeruginosa.
AB  - Bacteria attached to a surface are generally more tolerant to antibiotics than
      their planktonic counterparts, even without the formation of a biofilm. The
      mechanism of antibiotic tolerance in biofilm communities is multifactorial, and
      the genetic background underlying this antibiotic tolerance has not yet been
      fully elucidated. Using transposon mutagenesis, we isolated a mutant with reduced
      tolerance to biapenem (relative to that of the wild type) from adherent cells.
      Sequencing analysis revealed a mutation in the pslL gene, which is part of the
      polysaccharide biosynthesis operon. The Pseudomonas aeruginosa PAO1DeltapslBCD
      mutant demonstrated a 100-fold-lower survival rate during the exposure of
      planktonic and biofilm cells to biapenem; a similar phenotype was observed in a
      mouse infection model and in clinical strains. Transcriptional analysis of
      adherent cells revealed increased expression of both pslA and pelA, which are
      directly regulated by bis-(3',5')-cyclic dimeric GMP (c-di-GMP). Inactivation of
      wspF resulted in significantly increased tolerance to biapenem due to increased
      production of c-di-GMP. The loss of pslBCD in the DeltawspF mutant background
      abolished the biapenem-tolerant phenotype of the DeltawspF mutant, underscoring
      the importance of psl in biapenem tolerance. Overexpression of PA2133, which can
      catalyze the degradation of c-di-GMP, led to a significant reduction in biapenem
      tolerance in adherent cells, indicating that c-di-GMP is essential in mediating
      the tolerance effect. The effect of pslBCD on antibiotic tolerance was evident,
      with 50- and 200-fold-lower survival in the presence of ofloxacin and tobramycin,
      respectively. We speculate that the psl genes, which are activated by surface
      adherence through elevated intracellular c-di-GMP levels, confer tolerance to
      antimicrobials.

PMID- 28438928
TI  - Impact of Health Care Exposure on Genotypic Antiseptic Tolerance in
      Staphylococcus aureus Infections in a Pediatric Population.
AB  - Staphylococcus aureus possessing either the smr gene or the qacA/B genes is
      associated with decreased susceptibility to chlorhexidine gluconate (CHG) and
      other antiseptics. Previous studies of antiseptic-tolerant staphylococci have
      focused largely on high-risk populations, and the exact role of health care
      exposure in the acquisition of these organisms is unclear. We sought to describe
      the risk factors and features of infection caused by antiseptic-tolerant S.
      aureus in a general pediatric population. Isolates were selected from an ongoing
      S. aureus surveillance study. Every third sequential isolate in the year 2014 was
      selected for inclusion. All isolates underwent PCR for the genes qacA/B and smr
      Medical records were reviewed. Five hundred six isolates were included in the
      study, with 377 (74.3%) being community acquired. One hundred (19.8%) isolates
      were smr positive and 79 (15.6%) qacA/B positive. In univariable analyses, the
      presence of either gene was associated with underlying medical conditions,
      nosocomial acquisition, recent hospitalization, central venous lines, and CHG
      exposure. In multivariable analyses, only differences between patients with
      chronic medical conditions (odds ratio [OR] = 1.72; 95% confidence interval [CI],
      1.22 to 2.64) and nosocomial acquisition (OR = 2.48; 95% CI, 1.16 to 8.17)
      remained statistically significant. Among patients without risk factors, 27.9%
      had infection with an antiseptic-tolerant isolate. smr- or qacA/B-positive S.
      aureus isolates are common in children and are independently associated with
      nosocomial acquisition and underlying medical conditions. These findings imply a
      role for the health care environment in acquisition of these organisms. However,
      genotypic antiseptic tolerance was seen in >25% of healthy children with an S.
      aureus infection, indicating that these organism are prevalent in the community
      as well.

PMID- 28438929
TI  - Molecular Profile of Malaria Drug Resistance Markers of Plasmodium falciparum in
      Suriname.
AB  - In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently
      conducted to evaluate partial artemisinin resistance emerging in Plasmodium
      falciparum We genotyped the PfK13 propeller domain of P. falciparum in 40 samples
      as well as other mutations proposed to be associated with artemisinin-resistant
      mutants. We did not find any mutations previously associated with artemisinin
      resistance in Southeast Asia, but we found fixed resistance mutations for
      chloroquine (CQ) and sulfadoxine-pyrimethamine. Additionally, the PfCRT C350R
      mutation, associated with reversal of CQ resistance and piperaquine-selective
      pressure, was present in 62% of the samples. Our results from neutral
      microsatellite data also confirmed a high parasite gene flow in the Guiana
      Shield. Although recruiting participants for therapeutic efficacy studies is
      challenging in areas where malaria endemicity is very low due to the low number
      of malaria cases reported, conducting these studies along with molecular
      surveillance remains essential for the monitoring of artemisinin-resistant
      alleles and for the characterization of the population structure of P. falciparum
      in areas targeted for malaria elimination.

PMID- 28438930
TI  - In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against
      Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.
AB  - The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC)
      producers have led to increased clinical polymyxin use. Combination therapy with
      polymyxins may improve treatment outcomes, but it is uncertain which combinations
      are most effective. Clinical successes with intravenous minocycline-based
      combination treatments have been reported for infections caused by carbapenemase
      producing bacteria. The objective of this study was to evaluate the in vitro
      activity of polymyxin B and minocycline combination therapy against six KPC-2
      producing K. pneumoniae isolates (minocycline MIC range, 2 to 32 mg/liter).
      Polymyxin B monotherapy (0.5, 1, 2, 4, and 16 mg/liter) resulted in a rapid
      reduction of up to 6 log in bactericidal activity followed by regrowth by 24 h.
      Minocycline monotherapy (1, 2, 4, 8, and 16 mg/liter) showed no reduction of
      activity of >1.34 log against all isolates, although concentrations of 8 and 16
      mg/liter prolonged the time to regrowth. When the therapies were used in
      combination, rapid bactericidal activity was followed by slower regrowth, with
      synergy (60 of 120 combinations at 24 h, 19 of 120 combinations at 48 h) and
      additivity (43 of 120 combinations at 24 h, 44 of 120 combinations at 48 h)
      against all isolates. The extent of killing was greatest against the more
      susceptible polymyxin B isolates (MICs of <=0.5 mg/liter) regardless of the
      minocycline MIC. The pharmacodynamic activity of combined polymyxin B-minocycline
      therapy against KPC-producing K. pneumoniae is dependent on polymyxin B
      susceptibility. Further in vitro and animal studies must be performed to fully
      evaluate the efficacy of this drug combination.

PMID- 28438931
TI  - Identification of Antifungal H+-ATPase Inhibitors with Effect on Plasma Membrane
      Potential.
AB  - The plasma membrane H+-ATPase (Pma1) is an essential fungal protein and a
      proposed target for new antifungal medications. The compounds in a small-molecule
      library containing ~191,000 commercially available compounds were screened for
      their ability to inhibit Saccharomyces cerevisiae plasma membranes containing
      Pma1. The overall hit rate was 0.2%, corresponding to 407 compounds. These hit
      compounds were further evaluated for ATPase selectivity and broad-spectrum
      antifungal activity. Following this work, one Pma1 inhibitor series based on
      compound 14 and analogs was selected for further evaluation. This compound series
      was able to depolarize the membrane and inhibit extracellular acidification in
      intact fungal cells concomitantly with a significant increase in intracellular
      ATP levels. Collectively, we suggest that these effects may be a common feature
      of Pma1 inhibitors. Additionally, the work uncovered a dual mechanism for the
      previously identified cationic peptide BM2, revealing fungal membrane disruption,
      in addition to Pma1 inhibition. The methods presented here provide a solid
      platform for the evaluation of Pma1-specific inhibitors in a drug development
      setting. The present inhibitors could serve as a starting point for the
      development of new antifungal agents with a novel mode of action.

PMID- 28438932
TI  - Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV
      Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073.
AB  - Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and
      effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the
      performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs
      (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20
      ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV
      uninfected men and 8 seroconverters) who were enrolled in a study in the United
      States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men
      and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV
      uninfected men who accepted PrEP and samples from all 8 seroconverters were also
      tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit
      for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter
      samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208
      uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last
      study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were
      detected. The quantitative assay confirmed all positive results from the
      multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range,
      0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were
      detected in 4 of the 8 seroconverter samples. The multidrug assay had 100%
      sensitivity and specificity for detecting TFV and FTC at drug concentrations
      consistent with daily PrEP use. The quantitative assay detected TFV and FTC at
      lower levels, which also might have provided protection against HIV infection.

PMID- 28438934
TI  - Susceptibility of Imipenem-Susceptible but Meropenem-Resistant blaIMP-6-Carrying
      Enterobacteriaceae to Various Antibacterials, Including the Siderophore
      Cephalosporin Cefiderocol.

PMID- 28438933
TI  - Pyrazinoic Acid Inhibits a Bifunctional Enzyme in Mycobacterium tuberculosis.
AB  - Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment,
      acts as a key sterilizing drug. While the mechanism of activation of this prodrug
      into pyrazinoic acid (POA) by Mycobacterium tuberculosis has been extensively
      studied, not all molecular determinants that confer resistance to this mysterious
      drug have been identified. Here, we report how a new PZA resistance determinant,
      the Asp67Asn substitution in Rv2783, confers M. tuberculosis resistance to PZA.
      Expression of the mutant allele but not the wild-type allele in M. tuberculosis
      recapitulates the PZA resistance observed in clinical isolates. In addition to
      catalyzing the metabolism of RNA and single-stranded DNA, Rv2783 also metabolized
      ppGpp, an important signal transducer involved in the stringent response in
      bacteria. All catalytic activities of the wild-type Rv2783 but not the mutant
      were significantly inhibited by POA. These results, which indicate that Rv2783 is
      a target of PZA, provide new insight into the molecular mechanism of the
      sterilizing activity of this drug and a basis for improving the molecular
      diagnosis of PZA resistance and developing evolved PZA derivatives to enhance its
      antituberculosis activity.

PMID- 28438935
TI  - Candida guilliermondii Complex Is Characterized by High Antifungal Resistance but
      Low Mortality in 22 Cases of Candidemia.
AB  - The objectives of our study were to describe the characteristics of patients with
      Candida guilliermondii candidemia and to perform an in-depth microbiological
      characterization of isolates and compare them with those of patients with C.
      albicans candidemia. We described the risk factors and outcomes of 22 patients
      with candidemia caused by the C. guilliermondii complex. Incident isolates were
      identified using molecular techniques, and susceptibility to fluconazole,
      anidulafungin, and micafungin was studied. Biofilm formation was measured using
      the crystal violet assay (biomass production) and the XTT reduction assay
      (metabolic activity), and virulence was studied using the Galleria mellonella
      model. Biofilm formation was compared with that observed for C. albicans The main
      conditions predisposing to infection were malignancy (68%), immunosuppressive
      therapy (59%), and neutropenia (18%). Clinical presentation of candidemia was
      less severe in patients infected by the C. guilliermondii complex than in
      patients infected by C. albicans, and 30-day mortality was lower in C.
      guilliermondii patients (13.6% versus 33.9%, respectively; P = 0.049). Isolates
      were identified as C. guilliermondiisensu stricto (n = 17) and Candida fermentati
      (n = 5). The isolates produced biofilms with low metabolic activity and moderate
      biomass. The G. mellonella model showed that C. guilliermondii was less virulent
      than C. albicans (mean of 6 days versus 1 day of survival, respectively; P <
      0.001). Patients with candidemia caused by the C. guilliermondii complex had
      severe and debilitating underlying conditions. Overall, the isolates showed
      diminished susceptibility to fluconazole and echinocandins, although poor biofilm
      formation and the low virulence were associated with a favorable outcome.

PMID- 28438936
TI  - Demonstrating the Protective Efficacy of the Novel Fluoroquinolone Finafloxacin
      against an Inhalational Exposure to Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei is the causative agent of melioidosis, a serious
      disease endemic in Southeast Asia and Northern Australia. Antibiotic treatment is
      lengthy and relapse often occurs. Finafloxacin is a novel fluoroquinolone with
      increased antibacterial activity in acidic conditions in contrast to other
      fluoroquinolones which demonstrate reduced activity at a lower pH. Therefore,
      finafloxacin may have improved efficacy against B. pseudomallei, which can
      survive within host cells where the local pH is acidic. In vitro analysis was
      performed using MICs, minimal bactericidal concentrations (MBCs), time-kill
      assays, persister cell assays, and macrophage assays. Finafloxacin showed
      increased bactericidal activity at pH 5 in comparison to pH 7 and ciprofloxacin
      at pH 5. In vivo studies in BALB/c mice included pharmacokinetic studies to
      inform an appropriate dosing regimen. Finafloxacin efficacy was evaluated in an
      inhalational murine model of melioidosis where antibiotic treatment was initiated
      at 6 or 24 h postchallenge and continued for 14 days, and mice were observed for
      63 days. The survival of infected mice following 14 days of treatment was 80%,
      60% or 0% for treatments initiated at 6 h and 60%, 30% or 0% for treatments
      initiated at 24 h for finafloxacin, co-trimoxazole, or ciprofloxacin,
      respectively. In summary, finafloxacin has increased bactericidal activity for B.
      pseudomallei under acidic conditions in vitro and improves survival in a murine
      model of melioidosis compared with those for ciprofloxacin. Furthermore,
      finafloxacin improves bacteriological clearance compared with that of co
      trimoxazole, suggesting it may offer an effective postexposure prophylaxis
      against B. pseudomallei.

PMID- 28438937
TI  - IncX2 and IncX1-X2 Hybrid Plasmids Coexisting in a FosA6-Producing Escherichia
      coli Strain.
AB  - IncX plasmids are receiving much attention as vehicles of carbapenem and colistin
      resistance genes, such as blaNDM, blaKPC, and mcr-1 Among them, IncX2 subgroup
      plasmids remain rare. Here, we characterized IncX2 and IncX1-X2 hybrid plasmids
      coexisting in a FosA6-producing Escherichia coli strain that were possibly
      generated as a consequence of recombination events between an R6K-like IncX2
      plasmid and a pLN126_33-like IncX1 plasmid. Variable multidrug resistance mosaic
      regions were observed in these plasmids, indicating their potential to serve as
      flexible carriers of resistance genes. The diversity of IncX group plasmid
      backbones and accessory genes and the evolution of hybrid IncX plasmids pose a
      challenge in detecting and classifying them.

PMID- 28438938
TI  - A Tick Antivirulence Protein Potentiates Antibiotics against Staphylococcus
      aureus.
AB  - New strategies are needed to combat antibiotic resistance, especially against
      pathogens such as methicillin-resistant Staphylococcus aureus A tick antifreeze
      glycoprotein, IAFGP, possesses potent antibiofilm properties against a variety of
      clinical pathogens, including S. aureus Synergy between IAFGP, or a peptide (P1)
      representative of a repeat region of the protein, with different antibiotics was
      assessed in vitro Antibiotics that synergized with either IAFPG or P1 were
      further evaluated in vivo using vertebrate and invertebrate infection models.
      IAFGP readily enhanced the efficacy of antibiotics against S. aureus Synergy with
      daptomycin, an antibiotic used to treat methicillin-resistant S. aureus, was
      observed in vitro and in vivo using iafgp-transgenic mice and flies. Furthermore,
      synergy with ciprofloxacin or gentamicin, antibiotics not generally used to treat
      S. aureus, was also perceived. The combined effect of the antibiotic and IAFGP
      was associated with improved permeation of the antibiotic into the cell. Our
      results highlight that synergy of IAFGP with antibiotics traditionally used to
      treat this pathogen, and enhancement of the potency of antibiotics not commonly
      used against this microbe, can provide novel alternative therapeutic strategies
      to combat bacterial infections.

PMID- 28438940
TI  - Emergence of the Plasmid-Mediated mcr-1 Gene in Clinical KPC-2-Producing
      Klebsiella pneumoniae Sequence Type 392 in Brazil.

PMID- 28438939
TI  - Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both
      blaKPC and blaCTX-M Integrated in the Chromosome.
AB  - The extended-spectrum-beta-lactamase (ESBL)- and Klebsiella pneumoniae
      carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent
      threats to public health. In a retrospective study of multidrug-resistant K.
      pneumoniae, we identified three clinical isolates, CN1, CR14, and NY9, carrying
      both blaCTX-M and blaKPC genes. The complete genomes of these three K. pneumoniae
      isolates were de novo assembled by using both short- and long-read whole-genome
      sequencing. In CR14 and NY9, blaCTX-M and blaKPC were carried on two different
      plasmids. In contrast, CN1 had one copy of blaKPC-2 and three copies of blaCTX-M
      15 integrated in the chromosome, for which the blaCTX-M-15 genes were linked to
      an insertion sequence, ISEcp1, whereas the blaKPC-2 gene was in the context of a
      Tn4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly,
      downstream of the Tn4401a-blaKPC-2-prophage genomic island, CN1 also carried a
      clustered regularly interspaced short palindromic repeat (CRISPR)-cas array with
      four spacers targeting a variety of K. pneumoniae plasmids harboring
      antimicrobial resistance genes. Comparative genomic analysis revealed that there
      were two subtypes of type I-E CRISPR-cas in K. pneumoniae strains and suggested
      that the evolving CRISPR-cas, with its acquired novel spacer, induced the
      mobilization of antimicrobial resistance genes from plasmids into the chromosome.
      The integration and dissemination of multiple copies of blaCTX-M and blaKPC from
      plasmids to chromosome depicts the complex pandemic scenario of multidrug
      resistant K. pneumoniae Additionally, the implications from this study also raise
      concerns for the application of a CRISPR-cas strategy against antimicrobial
      resistance.

PMID- 28438941
TI  - New Macrolide-Lincosamide-Streptogramin B Resistance Gene erm(48) on the Novel
      Plasmid pJW2311 in Staphylococcus xylosus.
AB  - Whole-genome sequencing of Staphylococcus xylosus strain JW2311 from bovine
      mastitis milk identified the novel 49.3-kb macrolide-lincosamide-streptogramin B
      (MLSB) resistance plasmid pJW2311. It contained the macrolide resistance gene
      mph(C), the macrolide-streptogramin B resistance gene msr(A), and the new MLSB
      resistance gene erm(48) and could be transformed into Staphylococcus aureus by
      electroporation. Functionality of erm(48) was demonstrated by cloning and
      expression in S. aureus.

PMID- 28438942
TI  - Correlation between gyrA and CmeR Box Polymorphism and Fluoroquinolone Resistance
      in Campylobacter jejuni Isolates in China.
AB  - Sequence analysis of 79 ciprofloxacin-resistant Campylobacter jejuni isolates
      collected in China showed resistance-related sequence variations in gyrA and CmeR
      Box. All the isolates contain an identical Thr-86-Ile substitution in GyrA.
      Several novel CmeR-Box variations, including point substitutions, deletion, and
      insertion, were identified. The point insertion or deletion led to dramatically
      reduced binding of CmeR to the cmeABC promoter, which significantly increases the
      expression of cmeABC and contributes to the high fluoroquinolone resistance.

PMID- 28438943
TI  - Presence of VIM-Positive Pseudomonas Species in Chickens and Their Surrounding
      Environment.
AB  - Metallo-beta-lactamase gene blaVIM was identified on the chromosome of four
      Pseudomonas sp. isolates from a chicken farm, including one Pseudomonas
      aeruginosa isolate from a swallow (Yanornis martini), one Pseudomonas putida
      isolate from a fly, and two P. putida isolates from chickens. The four isolates
      shared two variants of blaVIM-carrying genomic contexts that resemble the
      corresponding regions of clinical metallo-beta-lactamase-producing Pseudomonas
      spp. Our study suggests that the surveillance of carbapenemase-producing bacteria
      in livestock and their surrounding environment is urgently needed.

PMID- 28438944
TI  - Genomic Insights into mcr-1-Positive Plasmids Carried by Colistin-Resistant
      Escherichia coli Isolates from Inpatients.

PMID- 28438945
TI  - Multihospital Occurrence of Pan-Resistant Klebsiella pneumoniae Sequence Type 147
      with an ISEcp1-Directed blaOXA-181 Insertion in the mgrB Gene in the United Arab
      Emirates.
AB  - The emergence of pan-resistant Klebsiella pneumoniae strains is an increasing
      concern. In the present study, we describe a cluster of 9 pan-resistant K.
      pneumoniae sequence type 147 (ST147) isolates encountered in 4 patients over
      nearly 1 year in 3 hospitals of the United Arab Emirates (UAE). The isolates
      exhibited highly similar genotypes. All produced chromosomally encoded OXA-181,
      and the majority also produced the NDM-5 carbapenemase. As with the previously
      described single isolate from the UAE, MS6671, the mgrB was disrupted by a
      functional, ISEcp1-driven blaOXA-181 insertion causing resistance to carbapenems.
      The mutation was successfully complemented with an intact mgrB gene, indicating
      that it was responsible for colistin resistance. blaNDM-5 was located within a
      resistance island of an approximately 100-kb IncFII plasmid carrying ermB,
      mph(A), blaTEM-1B, rmtB, blaNDM-5, sul1, aadA2, and dfrA12 resistance genes.
      Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly
      identical to that of plasmid pMS6671E from which several resistance genes,
      including blaNDM-5, had been deleted. More extensive similarities of the backbone
      and the resistance island were found between pABC143C-NDM and the blaNDM-5
      carrying IncFII plasmids of two K. pneumoniae ST147 isolates from South Korea,
      one of which was colistin resistant, and both also produced OXA-181. Notably, one
      of these strains was isolated from a patient transferred from the UAE. Our data
      show that this pan-resistant clone has an alarming capacity to maintain itself
      over an extended period of time and is even likely to be transmitted
      internationally.

PMID- 28438947
TI  - Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and
      Chemical Barrier Functions of Intestinal Epithelia.
AB  - We have shown previously that oral treatment with sodium butyrate or
      phenylbutyrate in an experimental model of shigellosis improves clinical outcomes
      and induces the expression of the antimicrobial peptide CAP-18 in the large
      intestinal epithelia. In a subsequent study, we found that entinostat, an
      aroylated phenylenediamine compound, has similar therapeutic potential against
      shigellosis. In this study, we aimed to evaluate entinostat as a potential
      candidate for host-directed therapy against cholera in an experimental model.
      Vibrio cholerae-infected rabbits were treated with two different dose regimens of
      entinostat: either 0.5 mg twice daily for 2 days or 1 mg once daily for 2 days.
      The effects of treatment on clinical outcomes and V. cholerae shedding (CFU count
      in stool) were observed. Immunohistochemical analysis was carried out to assess
      CAP-18 expression in ileal and jejunal mucosae. The serum zonulin level was
      measured by an enzyme-linked immunosorbent assay (ELISA) to evaluate gut
      permeability. Infection of rabbits with V. cholerae downregulated CAP-18
      expression in the ileal epithelium; the expression was replenished by oral
      treatment with entinostat at either dose regimen. The level of zonulin, a marker
      of gut permeability, in serum was upregulated after infection, and this
      upregulation was counteracted after treatment with entinostat. Entinostat
      treatment also led to recovery from cholera and a decline in the V. cholerae
      count in stool. In conclusion, the improved clinical outcome of cholera for
      rabbits treated with entinostat is associated with the induction of CAP-18 and
      the reduction of gut epithelial permeability.

PMID- 28438946
TI  - Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by
      Rose Bengal in In Vitro and In Vivo Studies.
AB  - Rose bengal (RB) is a halogenated xanthene dye that has been used to mediate
      antimicrobial photodynamic inactivation for several years. While RB is highly
      active against Gram-positive bacteria, it is largely inactive in killing Gram
      negative bacteria. We have discovered that addition of the nontoxic salt
      potassium iodide (100 mM) potentiates green light (540-nm)-mediated killing by up
      to 6 extra logs with the Gram-negative bacteria Escherichia coli and Pseudomonas
      aeruginosa, the Gram-positive bacterium methicillin-resistant Staphylococcus
      aureus, and the fungal yeast Candida albicans The mechanism is proposed to be
      singlet oxygen addition to iodide anion to form peroxyiodide, which decomposes
      into radicals and, finally, forms hydrogen peroxide and molecular iodine. The
      effects of these different bactericidal species can be teased apart by comparing
      the levels of killing achieved in three different scenarios: (i) cells, RB, and
      KI are mixed together and then illuminated with green light; (ii) cells and RB
      are centrifuged, and then KI is added and the mixture is illuminated with green
      light; and (iii) RB and KI are illuminated with green light, and then cells are
      added after illumination with the light. We also showed that KI could potentiate
      RB photodynamic therapy in a mouse model of skin abrasions infected with
      bioluminescent P. aeruginosa.

PMID- 28438948
TI  - Macrolide and quinolone-resistant Mycoplasma genitalium in a man with persistent
      urethritis: the tip of the British iceberg?
AB  - There is growing concern worldwide for macrolide resistance in M. genitalium
      following liberal use of 1 g azithromycin to treat non-gonococcal urethritis and
      confirmed C. trachomatis infection. Moxifloxacin is the second-line treatment for
      M. genitalium and still has excellent efficacy against it. However, recent
      reports indicating that quinolone resistance is more prevalent than previously
      thought are worrying. Routine testing of symptomatic men and women for M.
      genitalium is not currently recommended in BASHH guidelines, and attempts to
      implement such testing have been hampered by a lack of commercially available
      assays. We present a case of M. genitalium urethritis which failed to respond to
      four different antibiotic regimens, resulting in multiple visits to the clinic
      and anxiety for the patient.

PMID- 28438949
TI  - Dementia-friendly communities: where home care and mental health intersect.

PMID- 28438950
TI  - Toward ending hepatitis C virus infection: What are the next steps?

PMID- 28438951
TI  - Team-based versus traditional primary care models and short-term outcomes after
      hospital discharge.
AB  - BACKGROUND: Strategies to reduce hospital readmission have been studied mainly at
      the local level. We assessed associations between population-wide policies
      supporting team-based primary care delivery models and short-term outcomes after
      hospital discharge. METHODS: We extracted claims data on hospital admissions for
      any cause from 2002 to 2009 in the province of Quebec. We included older or
      chronically ill patients enrolled in team-based or traditional primary care
      practices. Outcomes were rates of readmission, emergency department visits and
      mortality in the 90 days following hospital discharge. We used inverse
      probability weighting to balance exposure groups on covariates and used marginal
      structural survival models to estimate rate differences and hazard ratios.
      RESULTS: We included 620 656 index admissions involving 312 377 patients.
      Readmission rates at any point in the 90-day post-discharge period were similar
      between primary care models. Patients enrolled in team-based primary care
      practices had lower 30-day rates of emergency department visits not associated
      with readmission (adjusted difference 7.5 per 1000 discharges, 95% confidence
      interval [CI] 4.2 to 10.8) and lower 30-day mortality (adjusted difference 3.8
      deaths per 1000 discharges, 95% CI 1.7 to 5.9). The 30-day difference for
      mortality differed according to morbidity level (moderate morbidity: 1.0 fewer
      deaths per 1000 discharges in team-based practices, 95% CI 0.3 more to 2.3 fewer
      deaths; very high morbidity: 4.2 fewer deaths per 1000 discharges, 95% CI 3.0 to
      5.3; p < 0.001). INTERPRETATION: Our study showed that enrolment in the newer
      team-based primary care practices was associated with lower rates of
      postdischarge emergency department visits and death. We did not observe
      differences in readmission rates, which suggests that more targeted or intensive
      efforts may be needed to affect this outcome.

PMID- 28438953
TI  - A 68-year-old man with an incidentally discovered pituitary lesion.

PMID- 28438952
TI  - Recommendations on hepatitis C screening for adults.

PMID- 28438954
TI  - Urinary tract infection in children.

PMID- 28438955
TI  - Ocular involvement in sarcoidosis.

PMID- 28438956
TI  - In good hands.

PMID- 28438957
TI  - Red hot foot ... keep Charcot arthropathy in mind.

PMID- 28438959
TI  - Litigious future for Big Sugar?

PMID- 28438958
TI  - Zopiclone overdose and flumazenil rescue.

PMID- 28438960
TI  - What "learning" machines will mean for medicine.

PMID- 28438961
TI  - Secrecy on cost of publicly funded hep C treatment.

PMID- 28438962
TI  - Stopping "steady stream" of overdose deaths a public health priority.

PMID- 28438963
TI  - Nearly a third of tests and treatments are unnecessary: CIHI.

PMID- 28438964
TI  - Grace in impossible places.

PMID- 28438965
TI  - Radiation induces proinflammatory dysbiosis: transmission of inflammatory
      susceptibility by host cytokine induction.
AB  - OBJECTIVE: Radiation proctitis (RP) is a complication of pelvic radiotherapy
      which affects both the host and microbiota. Herein we assessed the radiation
      effect on microbiota and its relationship to tissue damage using a rectal
      radiation mouse model. DESIGN: We evaluated luminal and mucosa-associated
      dysbiosis in irradiated and control mice at two postradiation time points and
      correlated it with clinical and immunological parameters. Epithelial cytokine
      response was evaluated using bacterial-epithelial co-cultures. Subsequently, germ
      free (GF) mice were colonised with postradiation microbiota and controls and
      exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1beta
      correlated with tissue damage and was induced by dysbiosis. Therefore, we tested
      its direct role in radiation-induced damage by IL-1 receptor antagonist
      administration to irradiated mice. RESULTS: A postradiation shift in microbiota
      was observed. A unique microbial signature correlated with histopathology.
      Increased colonic tumor necrosis factor (TNF)alpha, IL-1beta and IL-6 expression
      was observed at two different time points. Adherent microbiota from RP differed
      from those in uninvolved segments and was associated with tissue damage. Using
      bacterial-epithelial co-cultures, postradiation microbiota enhanced IL-1beta and
      TNFalpha expression compared with naive microbiota. GF mice colonisation by
      irradiated microbiota versus controls predisposed mice to both radiation injury
      and DSS-induced colitis. IL-1 receptor antagonist administration ameliorated
      intestinal radiation injury. CONCLUSIONS: The results demonstrate that rectal
      radiation induces dysbiosis, which transmits radiation and inflammatory
      susceptibility and provide evidence that microbial-induced radiation tissue
      damage is at least in part mediated by IL-1beta. Environmental factors may affect
      the host via modifications of the microbiome and potentially allow for novel
      interventional approaches via its manipulation.

PMID- 28438966
TI  - Mediation of Movement-Induced Breakthrough Cancer Pain by IB4-Binding Nociceptors
      in Rats.
AB  - Cancer-induced bone pain is characterized by moderate to severe ongoing pain that
      commonly requires the use of opiates. Even when ongoing pain is well controlled,
      patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks
      through" the medication. We developed a novel model of cancer-induced BTP using
      female rats with mammary adenocarcinoma cells sealed within the tibia. We
      demonstrated previously that rats with bone cancer learn to prefer a context
      paired with saphenous nerve block to elicit pain relief (i.e., conditioned place
      preference, CPP), revealing the presence of ongoing pain. Treatment with systemic
      morphine abolished CPP to saphenous nerve block, demonstrating control of ongoing
      pain. Here, we show that pairing BTP induced by experimenter-induced movement of
      the tumor-bearing hindlimb with a context produces conditioned place avoidance
      (CPA) in rats treated with morphine to control ongoing pain, consistent with
      clinical observation of BTP. Preventing movement-induced afferent input by
      saphenous nerve block before, but not after, hindlimb movement blocked movement
      induced BTP. Ablation of isolectin B4 (IB4)-binding, but not TRPV1+, sensory
      afferents eliminated movement-induced BTP, suggesting that input from IB4-binding
      fibers mediates BTP. Identification of potential molecular targets specific to
      this population of fibers may allow for the development of peripherally
      restricted analgesics that control BTP and improve quality of life in patients
      with skeletal metastases.SIGNIFICANCE STATEMENT We present a novel preclinical
      measure of movement-induced breakthrough pain (BTP) that is observed in the
      presence of morphine controlling ongoing pain. Blockade of sensory input before
      movement prevented BTP, whereas nerve block after movement failed to reverse BTP.
      These observations indicate that blocking peripheral sensory input may prevent
      BTP and targeting central sites may be required for pain relief once BTP has been
      initiated. Preventing sensory input from TRPV1-expressing fibers failed to alter
      movement-induced BTP. In contrast, preventing sensory input from isolectin B4
      (IB4)-binding fibers blocked movement-induced BTP. Therefore, examining molecular
      targets on this population of nociceptive fibers may prove useful for developing
      an improved strategy for preventing BTP in cancer patients with skeletal
      metastases.

PMID- 28438967
TI  - Immune-Induced Fever Is Dependent on Local But Not Generalized Prostaglandin E2
      Synthesis in the Brain.
AB  - Fever occurs upon binding of prostaglandin E2 (PGE2) to EP3 receptors in the
      median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE2
      has not been clearly determined. Here, using mice of both sexes, we examined the
      role of local versus generalized PGE2 production in the brain for the febrile
      response. In wild-type mice and in mice with genetic deletion of the
      prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium,
      generated with an inducible CreERT2 under the Slco1c1 promoter, PGE2 levels in
      the CSF were only weakly related to the magnitude of the febrile response,
      whereas the PGE2 synthesizing capacity in the hypothalamus, as reflected in the
      levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune
      induced fever. Histological analysis showed that the deletion of cyclooxygenase-2
      in brain endothelial cells occurred preferentially in small- and medium-sized
      vessels deep in the brain parenchyma, such as in the hypothalamus, whereas larger
      vessels, and particularly those close to the neocortical surface and in the
      meninges, were left unaffected, hence leaving PGE2 synthesis largely intact in
      major parts of the brain while significantly reducing it in the region critical
      for the febrile response. Furthermore, injection of a virus vector expressing
      microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus
      of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevation
      in response to LPS. We conclude that the febrile response is dependent on local
      release of PGE2 onto its target neurons and not on the overall PGE2 production in
      the brain.SIGNIFICANCE STATEMENT By using mice with selective deletion of
      prostaglandin synthesis in brain endothelial cells, we demonstrate that local
      prostaglandin E2 (PGE2) production in deep brain areas, such as the hypothalamus,
      which is the site of thermoregulatory neurons, is critical for the febrile
      response to peripheral inflammation. In contrast, PGE2 production in other brain
      areas and the overall PGE2 level in the brain do not influence the febrile
      response. Furthermore, partly restoring the PGE2 synthesizing capacity in the
      anterior hypothalamus of mice lacking such capacity with a lentiviral vector
      resulted in a temperature elevation in response to LPS. These data imply that the
      febrile response is dependent on the local release of PGE2 onto its target
      neurons, possibly by a paracrine mechanism.

PMID- 28438968
TI  - Neural Mechanisms of Cognitive Dissonance (Revised): An EEG Study.
AB  - Cognitive dissonance theory suggests that our preferences are modulated by the
      mere act of choosing. A choice between two similarly valued alternatives creates
      psychological tension (cognitive dissonance) that is reduced by a postdecisional
      reevaluation of the alternatives. We measured EEG of human subjects during rest
      and free-choice paradigm. Our study demonstrates that choices associated with
      stronger cognitive dissonance trigger a larger negative frontocentral evoked
      response similar to error-related negativity, which has in turn been implicated
      in general performance monitoring. Furthermore, the amplitude of the evoked
      response is correlated with the reevaluation of the alternatives. We also found a
      link between individual neural dynamics (long-range temporal correlations) of the
      frontocentral cortices during rest and follow-up neural and behavioral effects of
      cognitive dissonance. Individuals with stronger resting-state long-range temporal
      correlations demonstrated a greater postdecisional reevaluation of the
      alternatives and larger evoked brain responses associated with stronger cognitive
      dissonance. Thus, our results suggest that cognitive dissonance is reflected in
      both resting-state and choice-related activity of the prefrontal cortex as part
      of the general performance-monitoring circuitry.SIGNIFICANCE STATEMENT Contrary
      to traditional decision theory, behavioral studies repeatedly demonstrate that
      our preferences are modulated by the mere act of choosing. Difficult choices
      generate psychological (cognitive) dissonance, which is reduced by the
      postdecisional devaluation of unchosen options. We found that decisions
      associated with a higher level of cognitive dissonance elicited a stronger
      negative frontocentral deflection that peaked ~60 ms after the response. This
      activity shares similar spatial and temporal features as error-related
      negativity, the electrophysiological correlate of performance monitoring.
      Furthermore, the frontocentral resting-state activity predicted the individual
      magnitude of preference change and the strength of cognitive dissonance-related
      neural activity.

PMID- 28438969
TI  - Intracellular, In Vivo, Dynamics of Thalamocortical Synapses in Visual Cortex.
AB  - Seminal studies of the thalamocortical circuit in the visual system of the cat
      have been central to our understanding of sensory encoding. However,
      thalamocortical synaptic properties remain poorly understood. We used paired
      recordings, in the lateral geniculate nucleus (LGN) and primary visual cortex
      (V1), to provide the first in vivo characterization of sensory-driven
      thalamocortical potentials in V1. The amplitudes of EPSPs we characterized were
      smaller than those previously reported in vitro Consistent with prior findings,
      connected LGN-V1 pairs were only found when their receptive fields (RFs)
      overlapped, and the probability of connection increased steeply with degree of RF
      overlap and response similarity. However, surprisingly, we found no relationship
      between EPSP amplitudes and the similarity of RFs or responses, suggesting
      different connectivity models for intracortical and thalamocortical circuits.
      Putative excitatory regular-spiking (RS) and inhibitory fast-spiking (FS) V1
      cells had similar EPSP characteristics, showing that in the visual system,
      feedforward excitation and inhibition are driven with equal strength by the
      thalamus. Similar to observations in the somatosensory cortex, FS V1 cells
      received less specific input from LGN. Finally, orientation tuning in V1 was not
      inherited from single presynaptic LGN cells, suggesting that it must emerge
      exclusively from the combined input of all presynaptic LGN cells. Our results
      help to decipher early visual encoding circuits and have immediate utility in
      providing physiological constraints to computational models of the visual
      system.SIGNIFICANCE STATEMENT To understand how the brain encodes the visual
      environment, we must understand the transfer of visual signals between various
      regions of the brain. Therefore, understanding synaptic dynamics is critical to
      our understanding of sensory encoding. This study provides the first
      characterization of visually evoked synaptic potentials between the visual
      thalamus and visual cortex in an intact animal. To record these potentials, we
      simultaneously recorded the extracellular potential of presynaptic thalamic cells
      and the intracellular potential of postsynaptic cortical cells in input layers of
      primary visual cortex. Our characterization of synaptic potentials in vivo
      disagreed with prior findings in vitro This study will increase our understanding
      of thalamocortical circuits and will improve computational models of visual
      encoding.

PMID- 28438971
TI  - The impact and efficacy of surveillance in patients with sarcoma of the
      extremities.
AB  - OBJECTIVES: In this cross sectional study, the impact and the efficacy of a
      surveillance programme for sarcomas of the extremities was analysed. METHODS: All
      patients who had treatment with curative intent for a high-grade sarcoma and were
      diagnosed before 2014 were included and followed for a minimum of two years.
      RESULTS: Of the 909 patients who had a review appointment in 2014, 131 were under
      review for a high-grade sarcoma of the extremities following treatment with
      curative intent. Of these patients, three patients died of disease, two patients
      died of other causes, 12 are alive, with disease, and 114 have no evidence of
      disease. The surveillance programme accounts for 14% of all review
      appointments.Four of five patients (80%) who developed local recurrence
      identified the recurrence themselves. Chest radiographs are adequate in
      identifying metastatic disease and 11 (73%) of metastases were diagnosed during a
      routine follow up visit. However, the chance of cure is small and only two
      patients were referred for a metastatectomy. Of these only one survived for more
      than two years.The mean time for developing metastatic disease and local
      recurrence was 2.0 and 3.9 years respectively. Once identified, the mean time to
      death was 2.1 years for patients with metastatic disease. CONCLUSIONS:
      Surveillance of sarcoma patients makes up a substantial amount of the workload of
      a sarcoma unit. The chance of cure following identification of local recurrence
      or metastatic disease, however, is small. Alternative methods of surveillance
      that allow better evaluation of the patient's needs are recommended.Cite this
      article: P. Cool, G. Cribb. The impact and efficacy of surveillance in patients
      with sarcoma of the extremities. Bone Joint Res 2017;6:224-230. DOI: 10.1302/2046
      3758.64.BJR-2016-0253.R1.

PMID- 28438970
TI  - The Severity of Vestibular Dysfunction in Deafness as a Determinant of Comorbid
      Hyperactivity or Anxiety.
AB  - Attention-deficit/hyperactivity disorder (ADHD) and anxiety-related disorders
      occur at rates 2-3 times higher in deaf compared with hearing children. Potential
      explanations for these elevated rates and the heterogeneity of behavioral
      disorders associated with deafness have usually focused on socio-environmental
      rather than biological effects. Children with the 22q11.2 deletion or duplication
      syndromes often display hearing loss and behavioral disorders, including ADHD and
      anxiety-related disorders. Here, we show that mouse mutants with either a gain or
      loss of function of the T-Box transcription factor gene, Tbx1, which lies within
      the 22q11.2 region and is responsible for most of the syndromic defects, exhibit
      inner ear defects and hyperactivity. Furthermore, we show that (1) inner ear
      dysfunction due to the tissue-specific loss of Tbx1 or Slc12a2, which encodes a
      sodium-potassium-chloride cotransporter and is also necessary for inner ear
      function, causes hyperactivity; (2) vestibular rather than auditory failure
      causes hyperactivity; and (3) the severity rather than the age of onset of
      vestibular dysfunction differentiates whether hyperactivity or anxiety co-occurs
      with inner ear dysfunction. Together, these findings highlight a biological link
      between inner ear dysfunction and behavioral disorders and how sensory
      abnormalities can contribute to the etiology of disorders traditionally
      considered of cerebral origin.SIGNIFICANCE STATEMENT This study examines the
      biological rather than socio-environmental reasons why hyperactivity and anxiety
      disorders occur at higher rates in deaf individuals. Using conditional genetic
      approaches in mice, the authors show that (1) inner ear dysfunction due to either
      Tbx1 or Slc12a2 mutations cause hyperactivity; (2) it is vestibular dysfunction,
      which frequently co-occurs with deafness but often remains undiagnosed, rather
      than auditory dysfunction that causes hyperactivity and anxiety-related symptoms;
      and (3) the severity of vestibular dysfunction can predict whether hyperactivity
      or anxiety coexist with inner ear dysfunction. These findings suggest a need to
      evaluate vestibular function in hearing impaired individuals, especially those
      who exhibit hyperactive and anxiety-related symptoms.

PMID- 28438972
TI  - Position of O-Acetylation within the Capsular Repeat Unit Impacts the Biological
      Properties of Pneumococcal Serotypes 33A and 33F.
AB  - Streptococcus pneumoniae (pneumococcus) produces many capsule types that differ
      in their abilities to evade host immune recognition. To explain these serotype
      dependent protective capacities, many studies have investigated capsular
      thickness or the interaction of the capsule with complement proteins, but the
      effects of small chemical modifications of the capsule on its function have not
      been studied. One small chemical modification found frequently among pneumococcal
      capsules is O-acetylation. Pneumococcal serotype 33A has two membrane-bound O
      acetyltransferase genes, wciG and wcjE A 33A wcjE-deficient variant, 33F, occurs
      naturally and is increasing in prevalence in the wake of widespread conjugate
      vaccine use, but no wciG-deficient variants have been reported. To study the
      biological consequence of the loss of O-acetylation, we created wciG-deficient
      variants in both serotypes 33A and 33F, which we named 33X1 (DeltawciG) and 33X2
      (DeltawciG DeltawcjE). Serotypes 33X1 and 33X2 express novel capsule types based
      on serological and biochemical analyses. We found that loss of WcjE-mediated O
      acetylation appears not to affect cell wall shielding, since serotypes 33A and
      33F exhibit comparable nonspecific opsonophagocytic killing, biofilm production,
      and adhesion to nasopharyngeal cells, though serotype 33F survived short-term
      drying better than serotype 33A. Loss of WciG-mediated O-acetylation in serotypes
      33X1 and 33X2, however, resulted in a phenotype resembling that of
      nonencapsulated strains: increased cell wall accessibility, increased nonspecific
      opsonophagocytic killing, enhanced biofilm formation, and increased adhesion to
      nasopharyngeal cells. We conclude that WciG-mediated, but not WcjE-mediated, O
      acetylation is important for producing protective capsules in 33A and that small
      chemical changes to the capsule can drastically affect its biological properties.

PMID- 28438974
TI  - Bacillus anthracis Edema Toxin Increases Fractional Free Water and Sodium
      Reabsorption in an Isolated Perfused Rat Kidney Model.
AB  - Bacillus anthracis edema toxin (ET) consists of protective antigen (PA),
      necessary for host cell toxin uptake, and edema factor (EF), the toxic moiety
      which increases host cell cyclic AMP (cAMP). Since vasopressin stimulates renal
      water and sodium reabsorption via increased tubular cell cAMP levels, we
      hypothesized the ET would also do so. To test this hypothesis, we employed an
      isolated perfused rat kidney model. Kidneys were isolated and perfused with
      modified Krebs-Henseleit buffer. Perfusate and urine samples were obtained at
      baseline and every 10 min over 150 min following the addition of challenges with
      or without treatments to the perfusate. In kidneys perfused under constant flow
      or constant pressure, compared to PA challenge (n = 14 or 15 kidneys,
      respectively), ET (13 or 15 kidneys, respectively) progressively increased urine
      cAMP levels, water and sodium reabsorption, and urine osmolality and decreased
      urine output (P <= 0.04, except for sodium reabsorption under constant pressure
      [P = 0.17]). In ET-challenged kidneys, compared to placebo treatment, adefovir,
      an EF inhibitor, decreased urine cAMP levels, water and sodium reabsorption, and
      urine osmolality and increased urine output, while raxibacumab, a PA-directed
      monoclonal antibody (MAb), decreased urine cAMP levels, free water reabsorption,
      and urine osmolality and increased urine output (P <= 0.03 except for urine
      output with raxibacumab [P = 0.17]). Upon immunohistochemistry, aquaporin 2 was
      concentrated along the apical membrane of tubular cells with ET but not PA, and
      urine aquaporin 2 levels were higher with ET (5.52 +/- 1.06 ng/ml versus 1.51 +/-
      0.44 ng/ml [means +/- standard errors of the means {SEM}; P = 0.0001). Edema
      toxin has renal effects that could contribute to extravascular fluid collection
      characterizing anthrax infection clinically.

PMID- 28438973
TI  - Pulmonary Interleukin-17-Positive Lymphocytes Increase during Pneumocystis murina
      Infection but Are Not Required for Clearance of Pneumocystis.
AB  - Pneumocystis remains an important pathogen of immunosuppressed patients, causing
      a potentially life-threatening pneumonia. Despite its medical importance, the
      immune responses required to control infection, including the role of interleukin
      17 (IL-17), which is important in controlling other fungal infections, have not
      been clearly defined. Using flow cytometry and intracellular cytokine staining
      after stimulation with phorbol myristate acetate and ionomycin, we examined gamma
      interferon (IFN-gamma), IL-4, IL-5, and IL-17 production by lung lymphocytes in
      immunocompetent C57BL/6 mice over time following infection with
      Pneumocystismurina We also examined the clearance of Pneumocystis infection in IL
      17A-deficient mice. The production of both IFN-gamma and IL-17 by pulmonary
      lymphocytes increased during infection, with maximum production at approximately
      days 35 to 40, coinciding with peak Pneumocystis levels in the lungs, while
      minimal changes were seen in IL-4- and IL-5-positive cells. The proportion of
      cells producing IFN-gamma was consistently higher than for cells producing IL-17,
      with peak levels of ~25 to 30% of CD3+ T cells for the former compared to ~15%
      for the latter. Both CD4+ T cells and gammadelta T cells produced IL-17.
      Administration of anti-IFN-gamma antibody led to a decrease in IFN-gamma-positive
      cells, and an increase in IL-5-positive cells, but did not impact clearance of
      Pneumocystis infection. Despite the increases in IL-17 production during
      infection, IL-17A-deficient mice cleared Pneumocystis infection with kinetics
      similar to C57BL/6 mice. Thus, while IL-17 production in the lungs is increased
      during Pneumocystis infection in immunocompetent mice, IL-17A is not required for
      control of Pneumocystis infection.

PMID- 28438976
TI  - Chemical Attenuation in the Development of a Whole-Organism Malaria Vaccine.
AB  - Malaria vaccine development has been dominated by the subunit approach; however,
      many subunit vaccine candidates have had limited efficacy in settings of malaria
      endemicity. As our search for an efficacious malaria vaccine continues, the
      development of a whole-organism vaccine is now receiving much scrutiny. One
      strategy currently being explored in the development of a whole-organism vaccine
      involves chemical attenuation of the malaria parasite. In vivo and in vitro
      chemical attenuation of both liver-stage and blood-stage Plasmodium parasites has
      been investigated. Here, we discuss both approaches of chemical attenuation in
      the development of a whole-organism vaccine against malaria.

PMID- 28438975
TI  - Galectin-3 Is a Target for Proteases Involved in the Virulence of Staphylococcus
      aureus.
AB  - Staphylococcus aureus is a major cause of skin and soft tissue infection. The
      bacterium expresses four major proteases that are emerging as virulence factors:
      aureolysin (Aur), V8 protease (SspA), staphopain A (ScpA), and staphopain B
      (SspB). We hypothesized that human galectin-3, a beta-galactoside-binding lectin
      involved in immune regulation and antimicrobial defense, is a target for these
      proteases and that proteolysis of galectin-3 is a novel immune evasion mechanism.
      Indeed, supernatants from laboratory strains and clinical isolates of S. aureus
      caused galectin-3 degradation. Similar proteolytic capacities were found in
      Staphylococcus epidermidis isolates but not in Staphylococcus saprophyticus
      Galectin-3-induced activation of the neutrophil NADPH oxidase was abrogated by
      bacterium-derived proteolysis of galectin-3, and SspB was identified as the major
      protease responsible. The impact of galectin-3 and protease expression on S.
      aureus virulence was studied in a murine skin infection model. In galectin-3+/+
      mice, SspB-expressing S. aureus caused larger lesions and resulted in higher
      bacterial loads than protease-lacking bacteria. No such difference in bacterial
      load or lesion size was detected in galectin-3-/- mice, which overall showed
      smaller lesion sizes than the galectin-3+/+ animals. In conclusion, the
      staphylococcal protease SspB inactivates galectin-3, abrogating its stimulation
      of oxygen radical production in human neutrophils and increasing tissue damage
      during skin infection.

PMID- 28438977
TI  - 47 Years of IAI: a Glance in the Mirror and the Road Ahead.

PMID- 28438978
TI  - Peptoanaerobacter stomatis Primes Human Neutrophils and Induces Granule
      Exocytosis.
AB  - Peptoanaerobacter stomatis is a newly appreciated taxon associated with
      periodontal diseases; however, little is known about the organism's pathogenic
      potential or its interaction with the host immune response. Neutrophils are the
      most abundant innate immune cell present in the gingival tissue and function to
      constrain the oral microbial challenge. However, some periodontal pathogens have
      developed strategies to evade phagocytosis and killing by neutrophils. Therefore,
      to begin to understand the role of P. stomatis in periodontitis, we studied its
      interactions with human neutrophils. Our data showed that after 30 min of
      incubation, neutrophils failed to engulf P. stomatis efficiently; however, when
      P. stomatis was internalized, it was promptly eradicated. P. stomatis challenge
      induced a robust intracellular respiratory burst; however, this response did not
      contribute to bacterial killing. Minimal superoxide release was observed by
      direct bacterial challenge; however, P. stomatis significantly increased N-formyl
      methionyl-leucyl phenylalanine (fMLF)-stimulated superoxide release to an extent
      similar to that of cells primed with tumor necrosis factor alpha (TNF-alpha).
      When neutrophils were challenged with P. stomatis, 52% of the bacterium
      containing phagosomes were enriched for the specific granule marker lactoferrin
      and 82% with the azurophil granule marker elastase. P. stomatis challenge
      stimulated exocytosis of the four neutrophil granule subtypes. Moreover, P.
      stomatis susceptibility to extracellular killing could be attributed to the
      exocytosis of antimicrobial components present in neutrophil granules. Priming
      neutrophils for an enhanced respiratory burst together with promoting granule
      content release could contribute to the chronic inflammation and tissue
      destruction that characterize periodontal diseases.

PMID- 28438979
TI  - Infection and Immunity Welcomes the New Microbiology.

PMID- 28438980
TI  - Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to
      Coxiella burnetii Infection.
AB  - Coxiella burnetii is the causative agent of Q fever, a zoonotic disease that
      threatens both human and animal health. Due to the paucity of experimental animal
      models, little is known about how host factors interface with bacterial
      components and affect pathogenesis. Here, we used Drosophila melanogaster, in
      conjunction with the biosafety level 2 (BSL2) Nine Mile phase II (NMII) clone 4
      strain of C. burnetii, as a model to investigate host and bacterial components
      implicated in infection. We demonstrate that adult Drosophila flies are
      susceptible to C. burnetii NMII infection and that this bacterial strain, which
      activates the immune deficiency (IMD) pathway, is able to replicate and cause
      mortality in the animals. We show that in the absence of Eiger, the only known
      tumor necrosis factor (TNF) superfamily homolog in Drosophila, Coxiella-infected
      flies exhibit reduced mortality from infection. We also demonstrate that the
      Coxiella type 4 secretion system (T4SS) is critical for the formation of the
      Coxiella-containing vacuole and establishment of infection in Drosophila
      Altogether, our data reveal that the Drosophila TNF homolog Eiger and the
      Coxiella T4SS are implicated in the pathogenesis of C. burnetii in flies. The
      Drosophila/NMII model mimics relevant aspects of the infection in mammals, such
      as a critical role of host TNF and the bacterial T4SS in pathogenesis. Our work
      also demonstrates the usefulness of this BSL2 model to investigate both host and
      Coxiella components implicated in infection.

PMID- 28438981
TI  - Acute inflammation reveals GABAA receptor-mediated nociception in mouse dorsal
      root ganglion neurons via PGE2 receptor 4 signaling.
AB  - Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary
      afferent neurons through activation of Cl- permeable GABAA receptors but the
      physiologic role of GABAA receptors in the peripheral terminals of DRG neurons
      remains unclear. In this study, we investigated the role of peripheral GABAA
      receptors in nociception using a mouse model of acute inflammation. In vivo,
      peripheral administration of the selective GABAA receptor agonist muscimol evoked
      spontaneous licking behavior, as well as spinal wide dynamic range (WDR) neuron
      firing, after pre-conditioning with formalin but had no effect in saline-treated
      mice. GABAA receptor-mediated pain behavior after acute formalin treatment was
      abolished by the GABAA receptor blocker picrotoxin and cyclooxygenase inhibitor
      indomethacin. In addition, treatment with prostaglandin E2 (PGE2) was sufficient
      to reveal muscimol-induced licking behavior. In vitro, GABA induced sub-threshold
      depolarization in DRG neurons through GABAA receptor activation. Both formalin
      and PGE2 potentiated GABA-induced Ca2+ transients and membrane depolarization in
      capsaicin-sensitive nociceptive DRG neurons; these effects were blocked by the
      prostaglandin E2 receptor 4 (EP4) antagonist AH23848 (10 MUmol/L). Furthermore,
      potentiation of GABA responses by PGE2 was prevented by the selective Nav1.8
      antagonist A887826 (100 nmol/L). Although the function of the Na+-K+-2Cl- co
      transporter NKCC1 was required to maintain the Cl- ion gradient in isolated DRG
      neurons, NKCC1 was not required for GABAA receptor-mediated nociceptive behavior
      after acute inflammation. Taken together, these results demonstrate that GABAA
      receptors may contribute to the excitation of peripheral sensory neurons in
      inflammation through a combined effect involving PGE2-EP4 signaling and Na+
      channel sensitization.

PMID- 28438982
TI  - The histaminergic system is involved in psychological stress-induced hyperthermia
      in rats.
AB  - The histaminergic system modulates numerous physiological functions such as
      wakefulness, circadian rhythm, feeding, and thermoregulation. However, it is not
      yet known if this system is also involved in psychological stress-induced
      hyperthermia (PSH) and, if so, which histamine (H) receptor subtype mediates the
      effect. Therefore, we investigated the effects of pretreatments with
      intraperitoneal injections of mepyramine (an H1 receptor inverse agonist),
      cimetidine (an H2 receptor antagonist), and ciproxifan (an H3 receptor inverse
      agonist) on cage-exchange stress-induced hyperthermia (a model of PSH) by
      monitoring core body temperature (Tc) during both light (10:00 am-12:00 pm) and
      dark (10:00 pm-12:00 am) phases in conscious, freely moving rats. We also
      investigated the effects of these drugs on stress-induced changes in locomotor
      activity (La) to rule out the possibility that effects on Tc are achieved
      secondary to altered La Cage-exchange stress increased Tc within 20 min followed
      by a gradual decrease back to baseline Tc during both phases. In the light phase,
      mepyramine and cimetidine markedly attenuated PSH, whereas ciproxifan did not
      affect it. In contrast, in the dark phase, mepyramine dropped Tc by 1 degrees C
      without affecting cage-exchange stress-induced hyperthermia, whereas cimetidine
      and ciproxifan did not affect both postinjection Tc and PSH Cage-exchange stress
      induced an increase in La, especially in the light phase, but none of these drugs
      altered cage-exchange stress-induced La in either circadian rhythm phase. These
      results suggest that the histaminergic system is involved in the physiological
      mechanisms underlying PSH, particularly through H1 and H2 receptors, without
      influencing locomotor activity.

PMID- 28438983
TI  - Light-dependent expression of a Na+/H+ exchanger 3-like transporter in the
      ctenidium of the giant clam, Tridacna squamosa, can be related to increased H+
      excretion during light-enhanced calcification.
AB  - Na+/H+ exchangers (NHEs) regulate intracellular pH and ionic balance by mediating
      H+ efflux in exchange for Na+ uptake in a 1:1 stoichiometry. This study aimed to
      obtain from the ctenidium of the giant clam Tridacna squamosa (TS) the complete
      cDNA sequence of a NHE3-like transporter (TSNHE3), and to determine the effect of
      light exposure on its mRNA expression level and protein abundance therein. The
      coding sequence of TSNHE3 comprised 2886 bp, encoding 961 amino acids with an
      estimated molecular mass of 105.7 kDa. Immunofluorescence microscopy revealed
      that TSNHE3 was localized to the apical membrane of epithelial cells of the
      ctenidial filaments and the tertiary water channels. Particularly, the apical
      immunofluorescence of the ctenidial filaments was consistently stronger in the
      ctenidium of clams exposed to 12 h of light than those of the control kept in
      darkness. Indeed, light induced significant increases in the transcript level and
      protein abundance of TSNHE3/TSNHE3 in the ctenidium, indicating that the
      transcription and translation of TSNHE3/TSNHE3 were light-dependent. As light
      enhanced calcification generates H+, the increased expression of TSNHE3/TSNHE3 in
      the ctenidium could be a response to augment H+ excretion in pursuance of whole
      body acid-base balance during light exposure. These results signify that shell
      formation in giant clams requires the collaboration between the ctenidium, which
      is a respiratory and iono-regulatory organ, and the inner mantle, which is
      directly involved in the calcification process, and provide new insights into the
      mechanisms of light-enhanced calcification in giant clams.

PMID- 28438984
TI  - Comparison of multiple non-invasive methods of measuring cardiac output during
      pregnancy reveals marked heterogeneity in the magnitude of cardiac output change
      between women.
AB  - Various non-invasive methods are available to measure cardiac output (CO) during
      pregnancy. We compared serial measures of CO using various methods to determine
      which provided the least variability. Ten patients with spontaneous pregnancy had
      estimation of CO at baseline prior to becoming pregnant and at the end of the
      first and third trimesters. Echocardiographic data were used to estimate CO using
      the Teichholz method, Simpson's biplane method, and the Doppler determined
      velocity time integral (VTI) method. In addition, a Bioz Dx device was used to
      estimate CO by impedance cardiography. CO estimated with the VTI method had the
      lowest beat-to-beat variability. CO estimated with the VTI method was higher than
      CO estimated with the 2D-Teichholz method and Simpson's method. The percent
      change in CO during pregnancy was similar for all echo methods (VTI, Teichholz,
      and Simpson's biplane). Baseline CO determined with impedance cardiography was
      higher than CO determined with the VTI method. However, change in CO during
      pregnancy was significantly lower when measured with impedance cardiography.
      There was marked heterogeneity in the degree of rise in CO during the first
      trimester (-3 to 55%). The wide variation in the gestational rise in CO was
      unexpected, and at least in part secondary to variable increase in heart rate. We
      recommend the use of the Doppler determined VTI method for the estimation of CO
      in pregnancy.

PMID- 28438985
TI  - Decreased compliance in the deep and superficial conduit veins of the upper arm
      during prolonged cycling exercise.
AB  - We examined whether there is a difference in compliance between the deep and
      superficial conduit veins of the upper arm in response to prolonged exercise.
      Eight young men performed cycling exercise at 60% of peak oxygen uptake until
      rectal temperature had been increased by 1.1 degrees C for 38-48 min. The cross
      sectional area (CSA) of the brachial (deep) and basilic (superficial) veins was
      assessed by ultrasound during a cuff deflation protocol. Compliance (CPL) was
      calculated as the numerical derivative of the cuff pressure and CSA curve. During
      prolonged exercise, CPL in both conduit veins was similarly decreased when
      compared with pre-exercise values; however, the CSA decreased in the deep vein
      but increased in the superficial vein. In addition, passive heating caused an
      analogous change in CSA and CPL of superficial vein when compared with prolonged
      exercise, but did not change CSA and CPL of deep vein. Cold pressor test induced
      the decreased CSA of deep and superficial veins without the alteration of CPL of
      both veins. These results suggest that CPL in the deep and superficial conduit
      veins adjusts to prolonged exercise via different mechanisms.

PMID- 28438986
TI  - Transient enalapril attenuates the reduction in glomerular filtration rate in
      prenatally programmed rats.
AB  - A maternal low-protein diet has been shown to program hypertension and a
      reduction in glomerular filtration rate in adult offspring. This study examined
      the effect of continuous administration of enalapril in the drinking water and
      transient administration of enalapril administered from 21 to 42 days of age on
      blood pressure and glomerular filtration rate (GFR) in male rats whose mothers
      were fed a 20% protein diet (control) or a 6% protein diet (programmed) during
      the last half of pregnancy. After birth all rats were fed a 20% protein diet.
      Programmed rats (maternal 6% protein diet) were hypertensive at 15 months of age
      compared to control rats and both continuous and transient administration of
      enalapril had no effect on blood pressure on control offspring, but normalized
      the blood pressure of programmed offspring. GFR was 3.2 +/- 0.1 mL/min in the
      control group and 1.7 +/- 0.1 mL/min in the programmed rats at 17 months of age
      (P < 0.001). The GFR was 3.0 +/- 0.1 mL/min in the control and 2.7 +/- 0.1 mL/min
      in the programmed group that received continuous enalapril in their drinking
      water showing that enalapril can prevent the decrease in GFR in programmed rats.
      Transient administration of enalapril had no effect on GFR in the control group
      (3.2 +/- 0.1 mL/min) and prevented the decrease in GFR in the programmed group
      (2.9 +/- 0.1 mL/min). In conclusion, transient exposure to enalapril for 3 weeks
      after weaning can prevent the hypertension and decrease in GFR in prenatal
      programmed rats.

PMID- 28438987
TI  - Major trauma from suspected child abuse: a profile of the patient pathway.
AB  - BACKGROUND: Networked organised systems of care for patients with major trauma
      now exist in many countries, designed around the needs of the majority of
      patients (90% adults). Non-accidental injury is a significant cause of paediatric
      major trauma and has a different injury and age profile from accidental injury
      (AI). This paper compares the prehospital and inhospital phases of the patient
      pathway for children with suspected abuse, with those accidentally injured.
      METHODS: The paediatric database of the national trauma registry of England and
      Wales, Trauma Audit and Research Network, was interrogated from April 2012 (the
      launch of the major trauma networks) to June 2015, comparing the patient pathway
      for cases of suspected child abuse (SCA) with AI. RESULTS: In the study
      population of 7825 children, 7344 (94%) were classified as AI and 481 (6%) as
      SCA. SCA cases were younger (median 0.4 years vs 7 years for AI), had a higher
      Injury Severity Score (median 16vs9 for AI), and had nearly three times higher
      mortality (5.7%vs2.2% for AI). Other differences included presentation to
      hospital evenly throughout the day and year, arrival by non-ambulance means to
      hospital (74%) and delayed presentation to hospital from the time of injury
      (median 8 hours vs 1.8 hours for AI). Despite more severe injuries, these infants
      were less likely to receive key interventions in a timely manner. Only 20%
      arrived to a designated paediatric-capable major trauma centre. Secondary
      transfer to specialist care, if needed, took a median of 21.6 hours from
      injury(vs 13.8 hours for AI). CONCLUSION: These data show that children with
      major trauma that is inflicted rather than accidental follow a different pathway
      through the trauma system. The current model of major trauma care is not a good
      fit for the way in which child victims of suspected abuse present to healthcare.
      To achieve better care, awareness of this patient profile needs to increase, and
      trauma networks should adjust their conventional responses.

PMID- 28438988
TI  - The fading American dream: Trends in absolute income mobility since 1940.
AB  - We estimated rates of "absolute income mobility"-the fraction of children who
      earn more than their parents-by combining data from U.S. Census and Current
      Population Survey cross sections with panel data from de-identified tax records.
      We found that rates of absolute mobility have fallen from approximately 90% for
      children born in 1940 to 50% for children born in the 1980s. Increasing Gross
      Domestic Product (GDP) growth rates alone cannot restore absolute mobility to the
      rates experienced by children born in the 1940s. However, distributing current
      GDP growth more equally across income groups as in the 1940 birth cohort would
      reverse more than 70% of the decline in mobility. These results imply that
      reviving the "American dream" of high rates of absolute mobility would require
      economic growth that is shared more broadly across the income distribution.

PMID- 28438989
TI  - Documenting decline in U.S. economic mobility.

PMID- 28438990
TI  - Emergency admissions of children and young adults are rising, analysis shows.

PMID- 28438991
TI  - Differentiation of V2a interneurons from human pluripotent stem cells.
AB  - The spinal cord consists of multiple neuronal cell types that are critical to
      motor control and arise from distinct progenitor domains in the developing neural
      tube. Excitatory V2a interneurons in particular are an integral component of
      central pattern generators that control respiration and locomotion; however, the
      lack of a robust source of human V2a interneurons limits the ability to
      molecularly profile these cells and examine their therapeutic potential to treat
      spinal cord injury (SCI). Here, we report the directed differentiation of CHX10+
      V2a interneurons from human pluripotent stem cells (hPSCs). Signaling pathways
      (retinoic acid, sonic hedgehog, and Notch) that pattern the neural tube were
      sequentially perturbed to identify an optimized combination of small molecules
      that yielded ~25% CHX10+ cells in four hPSC lines. Differentiated cultures
      expressed much higher levels of V2a phenotypic markers (CHX10 and SOX14) than
      other neural lineage markers. Over time, CHX10+ cells expressed neuronal markers
      [neurofilament, NeuN, and vesicular glutamate transporter 2 (VGlut2)], and
      cultures exhibited increased action potential frequency. Single-cell RNAseq
      analysis confirmed CHX10+ cells within the differentiated population, which
      consisted primarily of neurons with some glial and neural progenitor cells. At 2
      wk after transplantation into the spinal cord of mice, hPSC-derived V2a cultures
      survived at the site of injection, coexpressed NeuN and VGlut2, extended neurites
      >5 mm, and formed putative synapses with host neurons. These results provide a
      description of V2a interneurons differentiated from hPSCs that may be used to
      model central nervous system development and serve as a potential cell therapy
      for SCI.

PMID- 28438993
TI  - Air quality, health, and climate implications of China's synthetic natural gas
      development.
AB  - Facing severe air pollution and growing dependence on natural gas imports, the
      Chinese government plans to increase coal-based synthetic natural gas (SNG)
      production. Although displacement of coal with SNG benefits air quality, it
      increases CO2 emissions. Due to variations in air pollutant and CO2 emission
      factors and energy efficiencies across sectors, coal replacement with SNG results
      in varying degrees of air quality benefits and climate penalties. We estimate air
      quality, human health, and climate impacts of SNG substitution strategies in
      2020. Using all production of SNG in the residential sector results in an annual
      decrease of ~32,000 (20,000 to 41,000) outdoor-air-pollution-associated premature
      deaths, with ranges determined by the low and high estimates of the health risks.
      If changes in indoor/household air pollution were also included, the decrease
      would be far larger. SNG deployment in the residential sector results in nearly
      10 and 60 times greater reduction in premature mortality than if it is deployed
      in the industrial or power sectors, respectively. Due to inefficiencies in
      current household coal use, utilization of SNG in the residential sector results
      in only 20 to 30% of the carbon penalty compared with using it in the industrial
      or power sectors. Even if carbon capture and storage is used in SNG production
      with today's technology, SNG emits 22 to 40% more CO2 than the same amount of
      conventional gas. Among the SNG deployment strategies we evaluate, allocating
      currently planned SNG to households provides the largest air quality and health
      benefits with the smallest carbon penalties.

PMID- 28438992
TI  - Microglial NFkappaB-TNFalpha hyperactivation induces obsessive-compulsive
      behavior in mouse models of progranulin-deficient frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is the second most common dementia before 65 years
      of age. Haploinsufficiency in the progranulin (GRN) gene accounts for 10% of all
      cases of familial FTD. GRN mutation carriers have an increased risk of autoimmune
      disorders, accompanied by elevated levels of tissue necrosis factor (TNF) alpha.
      We examined behavioral alterations related to obsessive-compulsive disorder (OCD)
      and the role of TNFalpha and related signaling pathways in FTD patients with GRN
      mutations and in mice lacking progranulin (PGRN). We found that patients and mice
      with GRN mutations displayed OCD and self-grooming (an OCD-like behavior in
      mice), respectively. Furthermore, medium spiny neurons in the nucleus accumbens,
      an area implicated in development of OCD, display hyperexcitability in PGRN
      knockout mice. Reducing levels of TNFalpha in PGRN knockout mice abolished
      excessive self-grooming and the associated hyperexcitability of medium spiny
      neurons of the nucleus accumbens. In the brain, PGRN is highly expressed in
      microglia, which are a major source of TNFalpha. We therefore deleted PGRN
      specifically in microglia and found that it was sufficient to induce excessive
      grooming. Importantly, excessive grooming in these mice was prevented by
      inactivating nuclear factor kappaB (NF-kappaB) in microglia/myeloid cells. Our
      findings suggest that PGRN deficiency leads to excessive NF-kappaB activation in
      microglia and elevated TNFalpha signaling, which in turn lead to
      hyperexcitability of medium spiny neurons and OCD-like behavior.

PMID- 28438994
TI  - Latently and uninfected healthcare workers exposed to TB make protective
      antibodies against Mycobacterium tuberculosis.
AB  - The role of Igs in natural protection against infection by Mycobacterium
      tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive
      immunization with mAbs generated against mycobacterial antigens has shown
      protective efficacy in murine models of infection, studies in B cell-depleted
      animals only showed modest phenotypes. We do not know if humans make protective
      antibody responses. Here, we investigated whether healthcare workers in a Beijing
      TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb,
      remain healthy-make antibody responses that are effective in protecting against
      infection by Mtb. We tested antibodies isolated from 48 healthcare workers and
      compared these with 12 patients with active TB. We found that antibodies from 7
      of 48 healthcare workers but none from active TB patients showed moderate
      protection against Mtb in an aerosol mouse challenge model. Intriguingly, three
      of seven healthcare workers who made protective antibody responses had no
      evidence of prior TB infection by IFN-gamma release assay. There was also good
      correlation between protection observed in vivo and neutralization of Mtb in an
      in vitro human whole-blood assay. Antibodies mediating protection were directed
      against the surface of Mtb and depended on both immune complexes and CD4+ T cells
      for efficacy. Our results indicate that certain individuals make protective
      antibodies against Mtb and challenge paradigms about the nature of an effective
      immune response to TB.

PMID- 28438995
TI  - csiLSFM combines light-sheet fluorescence microscopy and coherent structured
      illumination for a lateral resolution below 100 nm.
AB  - Light-sheet-based fluorescence microscopy (LSFM) features optical sectioning in
      the excitation process. It minimizes fluorophore bleaching as well as phototoxic
      effects and provides a true axial resolution. The detection path resembles
      properties of conventional fluorescence microscopy. Structured illumination
      microscopy (SIM) is attractive for superresolution because of its moderate
      excitation intensity, high acquisition speed, and compatibility with all
      fluorophores. We introduce SIM to LSFM because the combination pushes the lateral
      resolution to the physical limit of linear SIM. The instrument requires three
      objective lenses and relies on methods to control two counterpropagating coherent
      light sheets that generate excitation patterns in the focal plane of the
      detection lens. SIM patterns with the finest line spacing in the far field become
      available along multiple orientations. Flexible control of rotation, frequency,
      and phase shift of the perfectly modulated light sheet are demonstrated. Images
      of beads prove a near-isotropic lateral resolution of sub-100 nm. Images of yeast
      endoplasmic reticulum show that coherent structured illumination (csi) LSFM
      performs with physiologically relevant specimens.

PMID- 28438997
TI  - Nucleophilic water attack is not a possible mechanism for O-O bond formation in
      photosystem II.
AB  - Two different types of mechanisms are at present suggested for the O-O bond
      formation step in photosystem II. The first one is a coupling between an oxyl
      radical and a bridging oxo. The second one is a nucleophilic water attack on a
      terminal oxo (or oxyl) group. In the present short paper, the six most reasonable
      versions of the latter mechanism have been studied and compared with the oxo-oxyl
      mechanism. The barriers are found to be much too high for the water attack, and
      that mechanism can therefore safely be ruled out. The reason is that the
      protonated peroxide product is always very high in energy.

PMID- 28438996
TI  - Morphotype of bacteroids in different legumes correlates with the number and type
      of symbiotic NCR peptides.
AB  - In legume nodules, rhizobia differentiate into nitrogen-fixing forms called
      bacteroids, which are enclosed by a plant membrane in an organelle-like structure
      called the symbiosome. In the Inverted Repeat-Lacking Clade (IRLC) of legumes,
      this differentiation is terminal due to irreversible loss of cell division
      ability and is associated with genome amplification and different morphologies of
      the bacteroids that can be swollen, elongated, spherical, and elongated-branched,
      depending on the host plant. In Medicago truncatula, this process is orchestrated
      by nodule-specific cysteine-rich peptides (NCRs) delivered into developing
      bacteroids. Here, we identified the predicted NCR proteins in 10 legumes
      representing different subclades of the IRLC with distinct bacteroid morphotypes.
      Analysis of their expression and predicted sequences establishes correlations
      between the composition of the NCR family and the morphotypes of bacteroids.
      Although NCRs have a single origin, their evolution has followed different routes
      in individual lineages, and enrichment and diversification of cationic peptides
      has resulted in the ability to impose major morphological changes on the
      endosymbionts. The wide range of effects provoked by NCRs such as cell
      enlargement, membrane alterations and permeabilization, and biofilm and vesicle
      formation is dependent on the amino acid composition and charge of the peptides.
      These effects are strongly influenced by the rhizobial surface polysaccharides
      that affect NCR-induced differentiation and survival of rhizobia in nodule cells.

PMID- 28438998
TI  - Cas1 and the Csy complex are opposing regulators of Cas2/3 nuclease activity.
AB  - The type I-F CRISPR adaptive immune system in Pseudomonas aeruginosa (PA14)
      consists of two CRISPR loci and six CRISPR-associated (cas) genes. Type I-F
      systems rely on a CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to
      bind foreign DNA and recruit a trans-acting nuclease (i.e., Cas2/3) for target
      degradation. In most type I systems, Cas2 and Cas3 are separate proteins involved
      in adaptation and interference, respectively. However, in I-F systems, these
      proteins are fused into a single polypeptide. Here we use biochemical and
      structural methods to show that two molecules of Cas2/3 assemble with four
      molecules of Cas1 (Cas2/32:Cas14) into a four-lobed propeller-shaped structure,
      where the two Cas2 domains form a central hub (twofold axis of symmetry) flanked
      by two Cas1 lobes and two Cas3 lobes. We show that the Cas1 subunits repress
      Cas2/3 nuclease activity and that foreign DNA recognition by the Csy complex
      activates Cas2/3, resulting in bidirectional degradation of DNA targets.
      Collectively, this work provides a structure of the Cas1-2/3 complex and explains
      how Cas1 and the target-bound Csy complex play opposing roles in the regulation
      of Cas2/3 nuclease activity.

PMID- 28439000
TI  - Profile of Ian A. Wilson.

PMID- 28438999
TI  - Deciphering the sugar biosynthetic pathway and tailoring steps of nucleoside
      antibiotic A201A unveils a GDP-l-galactose mutase.
AB  - Galactose, a monosaccharide capable of assuming two possible configurational
      isomers (d-/l-), can exist as a six-membered ring, galactopyranose (Galp), or as
      a five-membered ring, galactofuranose (Galf). UDP-galactopyranose mutase (UGM)
      mediates the conversion of pyranose to furanose thereby providing a precursor for
      d-Galf Moreover, UGM is critical to the virulence of numerous eukaryotic and
      prokaryotic human pathogens and thus represents an excellent antimicrobial drug
      target. However, the biosynthetic mechanism and relevant enzymes that drive l
      Galf production have not yet been characterized. Herein we report that efforts to
      decipher the sugar biosynthetic pathway and tailoring steps en route to
      nucleoside antibiotic A201A led to the discovery of a GDP-l-galactose mutase,
      MtdL. Systematic inactivation of 18 of the 33 biosynthetic genes in the A201A
      cluster and elucidation of 10 congeners, coupled with feeding and in vitro
      biochemical experiments, enabled us to: (i) decipher the unique enzyme, GDP-l
      galactose mutase associated with production of two unique d-mannose-derived
      sugars, and (ii) assign two glycosyltransferases, four methyltransferases, and
      one desaturase that regiospecifically tailor the A201A scaffold and display
      relaxed substrate specificities. Taken together, these data provide important
      insight into the origin of l-Galf-containing natural product biosynthetic
      pathways with likely ramifications in other organisms and possible antimicrobial
      drug targeting strategies.

PMID- 28439001
TI  - Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by
      MyTH4-FERM myosins.
AB  - Unconventional myosin 7a (Myo7a), myosin 7b (Myo7b), and myosin 15a (Myo15a) all
      contain MyTH4-FERM domains (myosin tail homology 4-band 4.1, ezrin, radixin,
      moesin; MF) in their cargo binding tails and are essential for the growth and
      function of microvilli and stereocilia. Numerous mutations have been identified
      in the MyTH4-FERM tandems of these myosins in patients suffering visual and
      hearing impairment. Although a number of MF domain binding partners have been
      identified, the molecular basis of interactions with the C-terminal MF domain
      (CMF) of these myosins remains poorly understood. Here we report the high
      resolution crystal structure of Myo7b CMF in complex with the extended PDZ3
      domain of USH1C (a.k.a., Harmonin), revealing a previously uncharacterized
      interaction mode both for MyTH4-FERM tandems and for PDZ domains. We predicted,
      based on the structure of the Myo7b CMF/USH1C PDZ3 complex, and verified that
      Myo7a CMF also binds to USH1C PDZ3 using a similar mode. The structure of the
      Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness
      causing mutations in Myo7a CMF. Taken together, these findings suggest that
      binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common
      property of CMFs of Myo7a, Myo7b, and Myo15a.

PMID- 28439002
TI  - Reading a 400,000-year record of earthquake frequency for an intraplate fault.
AB  - Our understanding of the frequency of large earthquakes at timescales longer than
      instrumental and historical records is based mostly on paleoseismic studies of
      fast-moving plate-boundary faults. Similar study of intraplate faults has been
      limited until now, because intraplate earthquake recurrence intervals are
      generally long (10s to 100s of thousands of years) relative to conventional
      paleoseismic records determined by trenching. Long-term variations in the
      earthquake recurrence intervals of intraplate faults therefore are poorly
      understood. Longer paleoseismic records for intraplate faults are required both
      to better quantify their earthquake recurrence intervals and to test competing
      models of earthquake frequency (e.g., time-dependent, time-independent, and
      clustered). We present the results of U-Th dating of calcite veins in the Loma
      Blanca normal fault zone, Rio Grande rift, New Mexico, United States, that
      constrain earthquake recurrence intervals over much of the past ~550 ka-the
      longest direct record of seismic frequency documented for any fault to date. The
      13 distinct seismic events delineated by this effort demonstrate that for >400
      ka, the Loma Blanca fault produced periodic large earthquakes, consistent with a
      time-dependent model of earthquake recurrence. However, this time-dependent
      series was interrupted by a cluster of earthquakes at ~430 ka. The carbon isotope
      composition of calcite formed during this seismic cluster records rapid degassing
      of CO2, suggesting an interval of anomalous fluid source. In concert with U-Th
      dates recording decreased recurrence intervals, we infer seismicity during this
      interval records fault-valve behavior. These data provide insight into the long
      term seismic behavior of the Loma Blanca fault and, by inference, other
      intraplate faults.

PMID- 28439003
TI  - Numerical evidence for thermally induced monopoles.
AB  - Electric charges are conserved. The same would be expected to hold for magnetic
      charges, yet magnetic monopoles have never been observed. It is therefore
      surprising that the laws of nonequilibrium thermodynamics, combined with
      Maxwell's equations, suggest that colloidal particles heated or cooled in certain
      polar or paramagnetic solvents may behave as if they carry an electric/magnetic
      charge. Here, we present numerical simulations that show that the field
      distribution around a pair of such heated/cooled colloidal particles agrees
      quantitatively with the theoretical predictions for a pair of oppositely charged
      electric or magnetic monopoles. However, in other respects, the nonequilibrium
      colloidal particles do not behave as monopoles: They cannot be moved by a
      homogeneous applied field. The numerical evidence for the monopole-like fields
      around heated/cooled colloidal particles is crucial because the experimental and
      numerical determination of forces between such colloidal particles would be
      complicated by the presence of other effects, such as thermophoresis.

PMID- 28439004
TI  - Endocannabinoid system acts as a regulator of immune homeostasis in the gut.
AB  - Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized
      from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal
      cannabinoid that controls appetite and energy balance by engagement of the
      enteric nervous system through cannabinoid receptors. Here, we uncover a role for
      AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune
      tolerance in the gut and the pancreas. This work demonstrates a major
      immunological role for an endocannabinoid. The pungent molecule capsaicin (CP)
      has a similar effect as AEA; however, CP acts by engagement of the vanilloid
      receptor TRPV1, causing local production of AEA, which acts through CB2. We show
      that the engagement of the cannabinoid/vanilloid receptors augments the number
      and immune suppressive function of the regulatory CX3CR1hi macrophages (Mphi),
      which express the highest levels of such receptors among the gut immune cells.
      Additionally, TRPV1-/- or CB2-/- mice have fewer CX3CR1hi Mphi in the gut.
      Treatment of mice with CP also leads to differentiation of a regulatory subset of
      CD4+ cells, the Tr1 cells, in an IL-27-dependent manner in vitro and in vivo. In
      a functional demonstration, tolerance elicited by engagement of TRPV1 can be
      transferred to naive nonobese diabetic (NOD) mice [model of type 1 diabetes
      (T1D)] by transfer of CD4+ T cells. Further, oral administration of AEA to NOD
      mice provides protection from T1D. Our study unveils a role for the
      endocannabinoid system in maintaining immune homeostasis in the gut/pancreas and
      reveals a conversation between the nervous and immune systems using distinct
      receptors.

PMID- 28439005
TI  - Quantifying the influence of global warming on unprecedented extreme climate
      events.
AB  - Efforts to understand the influence of historical global warming on individual
      extreme climate events have increased over the past decade. However, despite
      substantial progress, events that are unprecedented in the local observational
      record remain a persistent challenge. Leveraging observations and a large climate
      model ensemble, we quantify uncertainty in the influence of global warming on the
      severity and probability of the historically hottest month, hottest day, driest
      year, and wettest 5-d period for different areas of the globe. We find that
      historical warming has increased the severity and probability of the hottest
      month and hottest day of the year at >80% of the available observational area.
      Our framework also suggests that the historical climate forcing has increased the
      probability of the driest year and wettest 5-d period at 57% and 41% of the
      observed area, respectively, although we note important caveats. For the most
      protracted hot and dry events, the strongest and most widespread contributions of
      anthropogenic climate forcing occur in the tropics, including increases in
      probability of at least a factor of 4 for the hottest month and at least a factor
      of 2 for the driest year. We also demonstrate the ability of our framework to
      systematically evaluate the role of dynamic and thermodynamic factors such as
      atmospheric circulation patterns and atmospheric water vapor, and find extremely
      high statistical confidence that anthropogenic forcing increased the probability
      of record-low Arctic sea ice extent.

PMID- 28439006
TI  - Murine model indicates 22q11.2 signaling adaptor CRKL is a dosage-sensitive
      regulator of genitourinary development.
AB  - The spectrum of congenital anomalies affecting either the upper tract (kidneys
      and ureters) or lower tract (reproductive organs) of the genitourinary (GU)
      system are fundamentally linked by the developmental origin of multiple GU
      tissues, including the kidneys, gonads, and reproductive ductal systems: the
      intermediate mesoderm. Although ~31% of DiGeorge/del22q11.2 syndrome patients
      exhibit GU defects, little focus has been placed on the molecular etiology of GU
      defects in this syndrome. Among del22q11.2 patients exhibiting GU anomalies, we
      have mapped the smallest relevant region to only five genes, including CRKLCRKL
      encodes a src-homology adaptor protein implicated in mediating tyrosine kinase
      signaling, and is expressed in the developing GU-tract in mice and humans. Here
      we show that Crkl mutant embryos exhibit gene dosage-dependent growth
      restriction, and homozygous mutants exhibit upper GU defects at a microdissection
      detectable rate of 23%. RNA-sequencing revealed that 52 genes are differentially
      regulated in response to uncoupling Crkl from its signaling pathways in the
      developing kidney, including a fivefold up-regulation of Foxd1, a known regulator
      of nephron progenitor differentiation. Additionally, Crkl heterozygous adult
      males exhibit cryptorchidism, lower testis weight, lower sperm count, and
      subfertility. Together, these data indicate that CRKL is intimately involved in
      normal development of both the upper and lower GU tracts, and disruption of CRKL
      contributes to the high incidence of GU defects associated with deletion at
      22q11.2.

PMID- 28439007
TI  - Ocean warming since 1982 has expanded the niche of toxic algal blooms in the
      North Atlantic and North Pacific oceans.
AB  - Global ocean temperatures are rising, yet the impacts of such changes on harmful
      algal blooms (HABs) are not fully understood. Here we used high-resolution sea
      surface temperature records (1982 to 2016) and temperature-dependent growth rates
      of two algae that produce potent biotoxins, Alexandrium fundyense and Dinophysis
      acuminata, to evaluate recent changes in these HABs. For both species, potential
      mean annual growth rates and duration of bloom seasons significantly increased
      within many coastal Atlantic regions between 40 degrees N and 60 degrees N, where
      incidents of these HABs have emerged and expanded in recent decades. Widespread
      trends were less evident across the North Pacific, although regions were
      identified across the Salish Sea and along the Alaskan coastline where blooms
      have recently emerged, and there have been significant increases in the potential
      growth rates and duration of these HAB events. We conclude that increasing ocean
      temperature is an important factor facilitating the intensification of these, and
      likely other, HABs and thus contributes to an expanding human health threat.

PMID- 28439008
TI  - Interaction of proliferating cell nuclear antigen with PMS2 is required for
      MutLalpha activation and function in mismatch repair.
AB  - Eukaryotic MutLalpha (mammalian MLH1-PMS2 heterodimer; MLH1-PMS1 in yeast)
      functions in early steps of mismatch repair as a latent endonuclease that
      requires a mismatch, MutSalpha/beta, and DNA-loaded proliferating cell nuclear
      antigen (PCNA) for activation. We show here that human PCNA and MutLalpha
      interact specifically but weakly in solution to form a complex of approximately
      1:1 stoichiometry that depends on PCNA interaction with the C-terminal
      endonuclease domain of the MutLalpha PMS2 subunit. Amino acid substitution
      mutations within a PMS2 C-terminal 721QRLIAP motif attenuate or abolish human
      MutLalpha interaction with PCNA, as well as PCNA-dependent activation of
      MutLalpha endonuclease, PCNA- and DNA-dependent activation of MutLalpha ATPase,
      and MutLalpha function in in vitro mismatch repair. Amino acid substitution
      mutations within the corresponding yeast PMS1 motif (723QKLIIP) reduce or abolish
      mismatch repair in vivo. Coupling of a weak allele within this motif (723AKLIIP)
      with an exo1Delta null mutation, which individually confer only weak mutator
      phenotypes, inactivates mismatch repair in the yeast cell.

PMID- 28439011
TI  - Correction for Naviaux et al., Metabolic features of chronic fatigue syndrome.

PMID- 28439009
TI  - Estrogen receptor beta, a regulator of androgen receptor signaling in the mouse
      ventral prostate.
AB  - As estrogen receptor beta-/- (ERbeta-/-) mice age, the ventral prostate (VP)
      develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory
      cells. To identify genes involved in these changes, we used RNA sequencing and
      immunohistochemistry to compare gene expression profiles in the VP of young (2-mo
      old) and aging (18-mo-old) ERbeta-/- mice and their WT littermates. We also
      treated young and old WT mice with an ERbeta-selective agonist and evaluated
      protein expression. The most significant findings were that ERbeta down-regulates
      androgen receptor (AR) signaling and up-regulates the tumor suppressor
      phosphatase and tensin homolog (PTEN). ERbeta agonist increased expression of the
      AR corepressor dachshund family (DACH1/2), T-cadherin, stromal caveolin-1, and
      nuclear PTEN and decreased expression of RAR-related orphan receptor c, Bcl2,
      inducible nitric oxide synthase, and IL-6. In the ERbeta-/- mouse VP, RNA
      sequencing revealed that the following genes were up-regulated more than
      fivefold: Bcl2, clusterin, the cytokines CXCL16 and -17, and a marker of
      basal/intermediate cells (prostate stem cell antigen) and cytokeratins 4, 5, and
      17. The most down-regulated genes were the following: the antioxidant gene
      glutathione peroxidase 3; protease inhibitors WAP four-disulfide core domain 3
      (WFDC3); the tumor-suppressive genes T-cadherin and caveolin-1; the regulator of
      transforming growth factor beta signaling SMAD7; and the PTEN ubiquitin ligase
      NEDD4. The role of ERbeta in opposing AR signaling, proliferation, and
      inflammation suggests that ERbeta-selective agonists may be used to prevent
      progression of prostate cancer, prevent fibrosis and development of benign
      prostatic hyperplasia, and treat prostatitis.

PMID- 28439010
TI  - CYCLOPS reveals human transcriptional rhythms in health and disease.
AB  - Circadian rhythms modulate many aspects of physiology. Knowledge of the molecular
      basis of these rhythms has exploded in the last 20 years. However, most of these
      data are from model organisms, and translation to clinical practice has been
      limited. Here, we present an approach to identify molecular rhythms in humans
      from thousands of unordered expression measurements. Our algorithm, cyclic
      ordering by periodic structure (CYCLOPS), uses evolutionary conservation and
      machine learning to identify elliptical structure in high-dimensional data. From
      this structure, CYCLOPS estimates the phase of each sample. We validated CYCLOPS
      using temporally ordered mouse and human data and demonstrated its consistency on
      human data from two independent research sites. We used this approach to identify
      rhythmic transcripts in human liver and lung, including hundreds of drug targets
      and disease genes. Importantly, for many genes, the circadian variation in
      expression exceeded variation from genetic and other environmental factors. We
      also analyzed hepatocellular carcinoma samples and show these solid tumors
      maintain circadian function but with aberrant output. Finally, to show how this
      method can catalyze medical translation, we show that dosage time can temporally
      segregate efficacy from dose-limiting toxicity of streptozocin, a
      chemotherapeutic drug. In sum, these data show the power of CYCLOPS and temporal
      reconstruction in bridging basic circadian research and clinical medicine.

PMID- 28439012
TI  - Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model
      of multiple sclerosis.
AB  - Environmental and hormonal factors are implicated in dysimmunity in multiple
      sclerosis. We investigated whether bisphenol-A, a prominent contaminant with
      endocrine-disrupting capabilities, altered susceptibility in an inflammatory
      model of multiple sclerosis. We found that gestational, but not adult, exposure
      to bisphenol-A increased the development of experimental autoimmune
      encephalomyelitis in adulthood in male, but not female, mice when a suboptimal
      disease-inducing immunization was used. Gestational bisphenol-A in male mice
      primed macrophages in adulthood and raised granulocyte-colony stimulating factor
      and neutrophil counts/activity postsuboptimal immunization. Neutralizing
      granulocyte-colony stimulating factor blocked susceptibility to disease in
      bisphenol-A mice. Early life exposure to bisphenol-A may represent an
      environmental consideration in multiple sclerosis.

PMID- 28439013
TI  - Biliary epithelial injury-induced regenerative response by IL-33 promotes
      cholangiocarcinogenesis from peribiliary glands.
AB  - The carcinogenic mechanism of extrahepatic cholangiocarcinoma (ECC) is unclear,
      due at least in part to the lack of an appropriate mouse model. Because human
      studies have reported frequent genetic alterations in the Ras- and TGFbeta/SMAD
      signaling pathways in ECC, mice with tamoxifen-inducible, duct-cell-specific Kras
      activation and a TGFbeta receptor type 2 (TGFbetaR2) deletion were first
      generated by crossing LSL-KrasG12D , Tgfbr2flox/flox , and K19CreERT mice (KT
      K19CreERT ). However, KT-K19CreERT mice showed only mild hyperplasia of biliary
      epithelial cells (BECs) in the extrahepatic bile duct (EHBD) and died within 7
      wk, probably a result of lung adenocarcinomas. Next, to analyze the additional
      effect of E-cadherin loss, KT-K19CreERT mice were crossed with CDH1flox/flox mice
      (KTC-K19CreERT ). Surprisingly, KTC-K19CreERT mice exhibited a markedly thickened
      EHBD wall accompanied by a swollen gallbladder within 4 wk after tamoxifen
      administration. Histologically, invasive periductal infiltrating-type ECC with
      lymphatic metastasis was observed. Time-course analysis of EHBD revealed that
      recombined BECs lining the bile duct lumen detached due to E-cadherin loss,
      whereas recombined cells could survive in the peribiliary glands (PBGs), which
      are considered a BEC stem-cell niche. Detached dying BECs released high levels of
      IL-33, as determined by microarray analysis using biliary organoids, and
      stimulated inflammation and a regenerative response by PBGs, leading eventually
      to ECC development. Cell lineage tracing suggested PBGs as the cellular origin of
      ECC. IL-33 cooperated with Kras and TGFbetaR2 mutations in the development of
      ECC, and anti-IL-33 treatment suppressed ECC development significantly. Thus,
      this mouse model provided insight into the carcinogenic mechanisms, cellular
      origin, and potential therapeutic targets of ECC.

PMID- 28439014
TI  - Brain networks for confidence weighting and hierarchical inference during
      probabilistic learning.
AB  - Learning is difficult when the world fluctuates randomly and ceaselessly.
      Classical learning algorithms, such as the delta rule with constant learning
      rate, are not optimal. Mathematically, the optimal learning rule requires
      weighting prior knowledge and incoming evidence according to their respective
      reliabilities. This "confidence weighting" implies the maintenance of an accurate
      estimate of the reliability of what has been learned. Here, using fMRI and an
      ideal-observer analysis, we demonstrate that the brain's learning algorithm
      relies on confidence weighting. While in the fMRI scanner, human adults attempted
      to learn the transition probabilities underlying an auditory or visual sequence,
      and reported their confidence in those estimates. They knew that these transition
      probabilities could change simultaneously at unpredicted moments, and therefore
      that the learning problem was inherently hierarchical. Subjective confidence
      reports tightly followed the predictions derived from the ideal observer. In
      particular, subjects managed to attach distinct levels of confidence to each
      learned transition probability, as required by Bayes-optimal inference. Distinct
      brain areas tracked the likelihood of new observations given current predictions,
      and the confidence in those predictions. Both signals were combined in the right
      inferior frontal gyrus, where they operated in agreement with the confidence
      weighting model. This brain region also presented signatures of a hierarchical
      process that disentangles distinct sources of uncertainty. Together, our results
      provide evidence that the sense of confidence is an essential ingredient of
      probabilistic learning in the human brain, and that the right inferior frontal
      gyrus hosts a confidence-based statistical learning algorithm for auditory and
      visual sequences.

PMID- 28439015
TI  - Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and
      Treslin.
AB  - Accumulating evidence supports the gain-of-function of mutant forms of p53
      (mutp53s). However, whether mutp53 directly perturbs the DNA replication
      checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a
      complex with mutp53s and mediates their gain-of-function through NF-Y and
      p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which
      inhibits its ATR-activating function. Here we show that various contact and
      conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate
      ATR checkpoint response during replication stress. The effect on ATR response
      caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion
      of another ATR activator, DNA2, in mutp53-R273H-expressing cancer cells renders
      cells hypersensitive to cisplatin. Expression of mutp53-R273H also makes cancer
      cells more sensitive to DNA2 depletion or DNA2 inhibitors. In addition to ATR
      activating function during replication stress, TopBP1 interacts with Treslin in a
      Cdk-dependent manner to initiate DNA replication during normal growth. We find
      that mutp53 also interferes with TopBP1 replication function. Several contact,
      but not conformational, mutp53s enhance the interaction between TopBP1 and
      Treslin and promote DNA replication despite the presence of a Cdk2 inhibitor.
      Together, these data uncover two distinct mechanisms by which mutp53 enhances DNA
      replication: (i) Both contact and conformational mutp53s can bind TopBP1 and
      attenuate the checkpoint response to replication stress, and (ii) during normal
      growth, contact (but not conformational) mutp53s can override the Cdk2
      requirement to promote replication by facilitating the TopBP1/Treslin
      interaction.

PMID- 28439017
TI  - Semibatch monomer addition as a general method to tune and enhance the mechanics
      of polymer networks via loop-defect control.
AB  - Controlling the molecular structure of amorphous cross-linked polymeric materials
      is a longstanding challenge. Herein, we disclose a general strategy for precise
      tuning of loop defects in covalent polymer gel networks. This "loop control" is
      achieved through a simple semibatch monomer addition protocol that can be applied
      to a broad range of network-forming reactions. By controlling loop defects, we
      demonstrate that with the same set of material precursors it is possible to tune
      and in several cases substantially improve network connectivity and mechanical
      properties (e.g., ~600% increase in shear storage modulus). We believe that the
      concept of loop control via continuous reagent addition could find broad
      application in the synthesis of academically and industrially important cross
      linked polymeric materials, such as resins and gels.

PMID- 28439016
TI  - Astrocytes locally translate transcripts in their peripheral processes.
AB  - Local translation in neuronal processes is key to the alteration of synaptic
      strength necessary for long-term potentiation, learning, and memory. Here, we
      present evidence that regulated de novo protein synthesis occurs within distal,
      perisynaptic astrocyte processes. Astrocyte ribosomal proteins are found adjacent
      to synapses in vivo, and immunofluorescent detection of peptide elongation in
      acute slices demonstrates robust translation in distal processes. We have also
      developed a biochemical approach to define candidate transcripts that are locally
      translated in astrocyte processes. Computational analyses indicate that astrocyte
      localized translation is both sequence-dependent and enriched for particular
      biological functions, such as fatty acid synthesis, and for pathways consistent
      with known roles for astrocyte processes, such as GABA and glutamate metabolism.
      These transcripts also include glial regulators of synaptic refinement, such as
      Sparc Finally, the transcripts contain a disproportionate amount of a binding
      motif for the quaking RNA binding protein, a sequence we show can significantly
      regulate mRNA localization and translation in the astrocytes. Overall, our
      observations raise the possibility that local production of astrocyte proteins
      may support microscale alterations of adjacent synapses.

PMID- 28439018
TI  - Conservation and divergence of C-terminal domain structure in the retinoblastoma
      protein family.
AB  - The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130
      negatively regulate cell proliferation by binding and inhibiting members of the
      E2F transcription factor family. The structural features that distinguish Rb from
      other pocket proteins have been unclear but are critical for understanding their
      functional diversity and determining why Rb has unique tumor suppressor
      activities. We describe here important differences in how the Rb and p107 C
      terminal domains (CTDs) associate with the coiled-coil and marked-box domains
      (CMs) of E2Fs. We find that although CTD-CM binding is conserved across protein
      families, Rb and p107 CTDs show clear preferences for different E2Fs. A crystal
      structure of the p107 CTD bound to E2F5 and its dimer partner DP1 reveals the
      molecular basis for pocket protein-E2F binding specificity and how cyclin
      dependent kinases differentially regulate pocket proteins through CTD
      phosphorylation. Our structural and biochemical data together with phylogenetic
      analyses of Rb and E2F proteins support the conclusion that Rb evolved specific
      structural motifs that confer its unique capacity to bind with high affinity
      those E2Fs that are the most potent activators of the cell cycle.

PMID- 28439019
TI  - Type I interferons induced by endogenous or exogenous viral infections promote
      metastasis and relapse of leishmaniasis.
AB  - The presence of the endogenous Leishmania RNA virus 1 (LRV1) replicating stably
      within some parasite species has been associated with the development of more
      severe forms of leishmaniasis and relapses after drug treatment in humans. Here,
      we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I
      IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice
      with the LRV1-cured Leishmania guyanensis (LgyLRV1- ) strain of parasites
      followed by type I IFN treatment increased lesion size and parasite burden,
      quantitatively reproducing the LRV1-bearing (LgyLRV1+ ) infection phenotype. This
      finding suggested the possibility that exogenous viral infections could likewise
      increase pathogenicity, which was tested by coinfecting mice with L. guyanensis
      and lymphocytic choriomeningitis virus (LCMV), or the sand fly-transmitted
      arbovirus Toscana virus (TOSV). The type I IFN antiviral response increased the
      pathology of L. guyanensis infection, accompanied by down-regulation of the IFN
      gamma receptor normally required for antileishmanial control. Further, LCMV
      coinfection of IFN-gamma-deficient mice promoted parasite dissemination to
      secondary sites, reproducing the LgyLRV1+ metastatic phenotype. Remarkably, LCMV
      coinfection of mice that had healed from L. guyanensis infection induced
      reactivation of disease pathology, overriding the protective adaptive immune
      response. Our findings establish that type I IFN-dependent responses, arising
      from endogenous viral elements (dsRNA/LRV1), or exogenous coinfection with IFN
      inducing viruses, are able to synergize with New World Leishmania parasites in
      both primary and relapse infections. Thus, viral infections likely represent a
      significant risk factor along with parasite and host factors, thereby
      contributing to the pathological spectrum of human leishmaniasis.

PMID- 28439021
TI  - Differences between measured and reported volatile organic compound emissions
      from oil sands facilities in Alberta, Canada.
AB  - Large-scale oil production from oil sands deposits in Alberta, Canada has raised
      concerns about environmental impacts, such as the magnitude of air pollution
      emissions. This paper reports compound emission rates (E) for 69-89 nonbiogenic
      volatile organic compounds (VOCs) for each of four surface mining facilities,
      determined with a top-down approach using aircraft measurements in the summer of
      2013. The aggregate emission rate (aE) of the nonbiogenic VOCs ranged from 50 +/-
      14 to 70 +/- 22 t/d depending on the facility. In comparison, equivalent VOC
      emission rates reported to the Canadian National Pollutant Release Inventory
      (NPRI) using accepted estimation methods were lower than the aE values by factors
      of 2.0 +/- 0.6, 3.1 +/- 1.1, 4.5 +/- 1.5, and 4.1 +/- 1.6 for the four
      facilities, indicating underestimation in the reported VOC emissions. For 11 of
      the combined 93 VOC species reported by all four facilities, the reported
      emission rate and E were similar; but for the other 82 species, the reported
      emission rate was lower than E The median ratio of E to that reported for all
      species by a facility ranged from 4.5 to 375 depending on the facility. Moreover,
      between 9 and 53 VOCs, for which there are existing reporting requirements to the
      NPRI, were not included in the facility emission reports. The comparisons between
      the emission reports and measurement-based emission rates indicate that
      improvements to VOC emission estimation methods would enhance the accuracy and
      completeness of emission estimates and their applicability to environmental
      impact assessments of oil sands developments.

PMID- 28439020
TI  - Mathematical model of chronic pancreatitis.
AB  - Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas,
      leading to its fibrotic destruction. There are currently no drugs that can stop
      or slow the progression of the disease. The etiology of the disease is
      multifactorial, whereas recurrent attacks of acute pancreatitis are thought to
      precede the development of CP. A better understanding of the pathology of CP is
      needed to facilitate improved diagnosis and treatment strategies for this
      disease. The present paper develops a mathematical model of CP based on a dynamic
      network that includes macrophages, pancreatic stellate cells, and prominent
      cytokines that are present at high levels in the CP microenvironment. The model
      is represented by a system of partial differential equations. The model is used
      to explore in silico potential drugs that could slow the progression of the
      disease, for example infliximab (anti-TNF-[Formula: see text]) and tocilizumab or
      siltuximab (anti-IL-6/IL-6R).

PMID- 28439022
TI  - Structure of a protective epitope of group B Streptococcus type III capsular
      polysaccharide.
AB  - Despite substantial progress in the prevention of group B Streptococcus (GBS)
      disease with the introduction of intrapartum antibiotic prophylaxis, this
      pathogen remains a leading cause of neonatal infection. Capsular polysaccharide
      conjugate vaccines have been tested in phase I/II clinical studies, showing
      promise for further development. Mapping of epitopes recognized by protective
      antibodies is crucial for understanding the mechanism of action of vaccines and
      for enabling antigen design. In this study, we report the structure of the
      epitope recognized by a monoclonal antibody with opsonophagocytic activity and
      representative of the protective response against type III GBS polysaccharide.
      The structure and the atomic-level interactions were determined by saturation
      transfer difference (STD)-NMR and X-ray crystallography using oligosaccharides
      obtained by synthetic and depolymerization procedures. The GBS PSIII epitope is
      made by six sugars. Four of them derive from two adjacent repeating units of the
      PSIII backbone and two of them from the branched galactose-sialic acid
      disaccharide contained in this sequence. The sialic acid residue establishes
      direct binding interactions with the functional antibody. The crystal structure
      provides insight into the molecular basis of antibody-carbohydrate interactions
      and confirms that the conformational epitope is not required for antigen
      recognition. Understanding the structural basis of immune recognition of capsular
      polysaccharide epitopes can aid in the design of novel glycoconjugate vaccines.

PMID- 28439023
TI  - Superconductivity and non-Fermi liquid behavior near a nematic quantum critical
      point.
AB  - Using determinantal quantum Monte Carlo, we compute the properties of a lattice
      model with spin [Formula: see text] itinerant electrons tuned through a quantum
      phase transition to an Ising nematic phase. The nematic fluctuations induce
      superconductivity with a broad dome in the superconducting [Formula: see text]
      enclosing the nematic quantum critical point. For temperatures above [Formula:
      see text], we see strikingly non-Fermi liquid behavior, including a "nodal
      antinodal dichotomy" reminiscent of that seen in several transition metal oxides.
      In addition, the critical fluctuations have a strong effect on the low-frequency
      optical conductivity, resulting in behavior consistent with "bad metal"
      phenomenology.

PMID- 28439024
TI  - NIP1;2 is a plasma membrane-localized transporter mediating aluminum uptake,
      translocation, and tolerance in Arabidopsis.
AB  - Members of the aquaporin (AQP) family have been suggested to transport aluminum
      (Al) in plants; however, the Al form transported by AQPs and the roles of AQPs in
      Al tolerance remain elusive. Here we report that NIP1;2, a plasma membrane
      localized member of the Arabidopsis nodulin 26-like intrinsic protein (NIP)
      subfamily of the AQP family, facilitates Al-malate transport from the root cell
      wall into the root symplasm, with subsequent Al xylem loading and root-to-shoot
      translocation, which are critical steps in an internal Al tolerance mechanism in
      Arabidopsis We found that NIP1;2 transcripts are expressed mainly in the root
      tips, and that this expression is enhanced by Al but not by other metal stresses.
      Mutations in NIP1;2 lead to hyperaccumulation of toxic Al3+ in the root cell
      wall, inhibition of root-to-shoot Al translocation, and a significant reduction
      in Al tolerance. NIP1;2 facilitates the transport of Al-malate, but not Al3+
      ions, in both yeast and Arabidopsis We demonstrate that the formation of the Al
      malate complex in the root tip apoplast is a prerequisite for NIP1;2-mediated Al
      removal from the root cell wall, and that this requires a functional root malate
      exudation system mediated by the Al-activated malate transporter, ALMT1. Taken
      together, these findings reveal a critical linkage between the previously
      identified Al exclusion mechanism based on root malate release and an internal Al
      tolerance mechanism identified here through the coordinated function of NIP1;2
      and ALMT1, which is required for Al removal from the root cell wall, root-to
      shoot Al translocation, and overall Al tolerance in Arabidopsis.

PMID- 28439025
TI  - Endocrine network essential for reproductive success in Drosophila melanogaster.
AB  - Ecdysis-triggering hormone (ETH) was originally discovered and characterized as a
      molt termination signal in insects through its regulation of the ecdysis
      sequence. Here we report that ETH persists in adult Drosophila melanogaster,
      where it functions as an obligatory allatotropin to promote juvenile hormone (JH)
      production and reproduction. ETH signaling deficits lead to sharply reduced JH
      levels and consequent reductions of ovary size, egg production, and yolk
      deposition in mature oocytes. Expression of ETH and ETH receptor genes is in turn
      dependent on ecdysone (20E). Furthermore, 20E receptor knockdown specifically in
      Inka cells reduces fecundity. Our findings indicate that the canonical
      developmental roles of 20E, ETH, and JH during juvenile stages are repurposed to
      function as an endocrine network essential for reproductive success.

PMID- 28439026
TI  - The SP100 component of ND10 enhances accumulation of PML and suppresses
      replication and the assembly of HSV replication compartments.
AB  - Nuclear domain 10 (ND10) bodies are small (0.1-1 MUM) nuclear structures
      containing both constant [e.g., promyelocytic leukemia protein (PML), SP100,
      death domain-associated protein (Daxx)] and variable proteins, depending on the
      function of the cells or the stress to which they are exposed. In herpes simplex
      virus (HSV)-infected cells, ND10 bodies assemble at the sites of DNA entering the
      nucleus after infection. In sequence, the ND10 bodies become viral replication
      compartments, and ICP0, a viral E3 ligase, degrades both PML and SP100. The
      amounts of PML and SP100 and the number of ND10 structures increase in cells
      exposed to IFN-beta. Earlier studies have shown that PML has three key functions.
      Thus, (i) the interaction of PML with viral components facilitates the initiation
      of replication compartments, (ii) viral replication is significantly less
      affected by IFN-beta in PML-/- cells than in parental PML+/+ cells, and (iii)
      viral yields are significantly lower in PML-/- cells exposed to low ratios of
      virus per cell compared with parental PML+/+ cells. This report focuses on the
      function of SP100. In contrast to PML-/- cells, SP100-/- cells retain the
      sensitivity of parental SP100+/+ cells to IFN-beta and support replication of the
      DeltaICP0 virus. At low multiplicities of infection, wild-type virus yields are
      higher in SP100-/- cells than in parental HEp-2 cells. In addition, the number of
      viral replication compartments is significantly higher in SP100-/- cells than in
      parental SP100+/+ cells or in PML-/- cells.

PMID- 28439027
TI  - Biochemical and structural characterization of oxygen-sensitive 2-thiouridine
      synthesis catalyzed by an iron-sulfur protein TtuA.
AB  - Two-thiouridine (s2U) at position 54 of transfer RNA (tRNA) is a
      posttranscriptional modification that enables thermophilic bacteria to survive in
      high-temperature environments. s2U is produced by the combined action of two
      proteins, 2-thiouridine synthetase TtuA and 2-thiouridine synthesis sulfur
      carrier protein TtuB, which act as a sulfur (S) transfer enzyme and a ubiquitin
      like S donor, respectively. Despite the accumulation of biochemical data in vivo,
      the enzymatic activity by TtuA/TtuB has rarely been observed in vitro, which has
      hindered examination of the molecular mechanism of S transfer. Here we
      demonstrate by spectroscopic, biochemical, and crystal structure analyses that
      TtuA requires oxygen-labile [4Fe-4S]-type iron (Fe)-S clusters for its enzymatic
      activity, which explains the previously observed inactivation of this enzyme in
      vitro. The [4Fe-4S] cluster was coordinated by three highly conserved cysteine
      residues, and one of the Fe atoms was exposed to the active site. Furthermore,
      the crystal structure of the TtuA-TtuB complex was determined at a resolution of
      2.5 A, which clearly shows the S transfer of TtuB to tRNA using its C-terminal
      thiocarboxylate group. The active site of TtuA is connected to the outside by two
      channels, one occupied by TtuB and the other used for tRNA binding. Based on
      these observations, we propose a molecular mechanism of S transfer by TtuA using
      the ubiquitin-like S donor and the [4Fe-4S] cluster.

PMID- 28439028
TI  - BGP-15 prevents the death of neurons in a mouse model of familial dysautonomia.
AB  - Hereditary sensory and autonomic neuropathy type III, or familial dysautonomia
      [FD; Online Mendelian Inheritance in Man (OMIM) 223900], affects the development
      and long-term viability of neurons in the peripheral nervous system (PNS) and
      retina. FD is caused by a point mutation in the gene IKBKAP/ELP1 that results in
      a tissue-specific reduction of the IKAP/ELP1 protein, a subunit of the Elongator
      complex. Hallmarks of the disease include vasomotor and cardiovascular
      instability and diminished pain and temperature sensation caused by reductions in
      sensory and autonomic neurons. It has been suggested but not demonstrated that
      mitochondrial function may be abnormal in FD. We previously generated an
      Ikbkap/Elp1 conditional-knockout mouse model that recapitulates the selective
      death of sensory (dorsal root ganglia) and autonomic neurons observed in FD. We
      now show that in these mice neuronal mitochondria have abnormal membrane
      potentials, produce elevated levels of reactive oxygen species, are fragmented,
      and do not aggregate normally at axonal branch points. The small hydroxylamine
      compound BGP-15 improved mitochondrial function, protecting neurons from dying in
      vitro and in vivo, and promoted cardiac innervation in vivo. Given that
      impairment of mitochondrial function is a common pathological component of
      neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's,
      Parkinson's, and Huntington's diseases, our findings identify a therapeutic
      approach that may have efficacy in multiple degenerative conditions.

PMID- 28439029
TI  - Melvin M. Grumbach 1925-2016.

PMID- 28439030
TI  - Epithelial EZH2 serves as an epigenetic determinant in experimental colitis by
      inhibiting TNFalpha-mediated inflammation and apoptosis.
AB  - Epithelial barrier disruption is a major cause of inflammatory bowel disease
      (IBD); however, the mechanism through which epigenetic regulation modulates
      intestinal epithelial integrity remains largely undefined. Here we show that
      EZH2, the catalytic subunit of polycomb repressive complex (PRC2), is
      indispensable for maintaining epithelial cell barrier integrity and homeostasis
      under inflammatory conditions. In accordance with reduced EZH2 expression in
      patients, the inactivation of EZH2 in IECs sensitizes mice to DSS- and TNBS
      induced experimental colitis. Conversely, EZH2 overexpression in the intestinal
      epithelium renders mice more resistant to colitis. Mechanistically, the genes
      encoding TRAF2/5 are held in a finely tuned bivalent status under inflammatory
      conditions. EZH2 deficiency potentiates the expression of these genes to enhance
      TNFalpha-induced NF-kappaB signaling, thereby leading to uncontrolled
      inflammation. More importantly, we show that EZH2 depletion compromises the
      protective role of NF-kappaB signaling in cell survival by directly up-regulating
      ITCH, a well-known E3 ligase that degrades the c-FLIP protein. Thus, our findings
      highlight an epigenetic mechanism by which EZH2 integrates the multifaceted
      effects of TNFalpha signaling to promote the inflammatory response and apoptosis
      in colitis.

PMID- 28439031
TI  - Explaining negative kin discrimination in a cooperative mammal society.
AB  - Kin selection theory predicts that, where kin discrimination is possible, animals
      should typically act more favorably toward closer genetic relatives and direct
      aggression toward less closely related individuals. Contrary to this prediction,
      we present data from an 18-y study of wild banded mongooses, Mungos mungo,
      showing that females that are more closely related to dominant individuals are
      specifically targeted for forcible eviction from the group, often suffering
      severe injury, and sometimes death, as a result. This pattern cannot be explained
      by inbreeding avoidance or as a response to more intense local competition among
      kin. Instead, we use game theory to show that such negative kin discrimination
      can be explained by selection for unrelated targets to invest more effort in
      resisting eviction. Consistent with our model, negative kin discrimination is
      restricted to eviction attempts of older females capable of resistance; dominants
      exhibit no kin discrimination when attempting to evict younger females, nor do
      they discriminate between more closely or less closely related young when
      carrying out infanticidal attacks on vulnerable infants who cannot defend
      themselves. We suggest that in contexts where recipients of selfish acts are
      capable of resistance, the usual prediction of positive kin discrimination can be
      reversed. Kin selection theory, as an explanation for social behavior, can
      benefit from much greater exploration of sequential social interactions.

PMID- 28439032
TI  - Inactivation of Transcriptional Regulators during Within-Household Evolution of
      Escherichia coli.
AB  - We analyzed the within-household evolution of two household-associated
      Escherichia coli strains from pandemic clonal group ST131-H30, using isolates
      recovered from five individuals within two families, each of which had a distinct
      strain. Family 1's strain was represented by a urine isolate from the index
      patient (older sister) with recurrent cystitis and a blood isolate from her
      younger sister with fatal urosepsis. Family 2's strain was represented by a urine
      isolate from the index patient (father) with pyelonephritis and renal abscesses,
      blood and kidney drainage isolates from the daughter with emphysematous
      pyelonephritis, and urine and fecal isolates from the mother with cystitis.
      Collectively, the several variants of each family's strain had accumulated a
      total of 8 (family 1) and 39 (family 2) point mutations; no two isolates were
      identical. Of the 47 total mutations, 36 resulted in amino acid changes or
      truncation of coded proteins. Fourteen such mutations (39%) targeted genes
      encoding transcriptional regulators, and 9 (25%) involved DNA-binding
      transcription factors (TFs), which significantly exceeded the relative
      contribution of TF genes to the isolates' genomes (~6%). At least one-half of the
      transcriptional regulator mutations were inactivating, based on phenotypic and/or
      transcriptional analysis. In particular, inactivating mutations in the global
      regulator LrhA (repressor of type 1 fimbriae and flagella) occurred in the blood
      isolates from both households and increased the virulence of E. coli strains in a
      murine sepsis model. The results indicate that E. coli undergoes adaptive
      evolution between and/or within hosts, generating subpopulations with distinctive
      phenotypes and virulence potential.IMPORTANCE The clonal evolution of bacterial
      strains associated with interhost transmission is poorly understood. We
      characterized the genome sequences of clonal descendants of two Escherichia coli
      strains, recovered at different time points from multiple individuals within two
      households who had different types of urinary tract infection. We found evidence
      that the E. coli strains underwent extensive mutational diversification between
      and within these individuals, driven disproportionately by inactivation of
      transcriptional regulators. In urosepsis isolates, the mutations observed in the
      global regulator LrhA increased bacterial virulence in a murine sepsis model. Our
      findings help in understanding the adaptive dynamics and strategies of E. coli
      during short-term natural evolution.

PMID- 28439033
TI  - Genome-Wide Analysis of ResD, NsrR, and Fur Binding in Bacillus subtilis during
      Anaerobic Fermentative Growth by In Vivo Footprinting.
AB  - Upon oxygen limitation, the Bacillus subtilis ResE sensor kinase and its cognate
      ResD response regulator play primary roles in the transcriptional activation of
      genes functioning in anaerobic respiration. The nitric oxide (NO)-sensitive NsrR
      repressor controls transcription to support nitrate respiration. In addition, the
      ferric uptake repressor (Fur) can modulate transcription under anaerobic
      conditions. However, whether these controls are direct or indirect has been
      investigated only in a gene-specific manner. To gain a genomic view of anaerobic
      gene regulation, we determined the genome-wide in vivo DNA binding of ResD, NsrR,
      and Fur transcription factors (TFs) using in situ DNase I footprinting combined
      with chromatin affinity precipitation sequencing (ChAP-seq; genome footprinting
      by high-throughput sequencing [GeF-seq]). A significant number of sites were
      targets of ResD and NsrR, and a majority of them were also bound by Fur. The
      binding of multiple TFs to overlapping targets affected each individual TF's
      binding, which led to combinatorial transcriptional control. ResD bound to both
      the promoters and the coding regions of genes under its positive control. Other
      genes showing enrichment of ResD at only the promoter regions are targets of
      direct ResD-dependent repression or antirepression. The results support previous
      findings of ResD as an RNA polymerase (RNAP)-binding protein and indicated that
      ResD can associate with the transcription elongation complex. The data set
      allowed us to reexamine consensus sequence motifs of Fur, ResD, and NsrR and
      uncovered evidence that multiple TGW (where W is A or T) sequences surrounded by
      an A- and T-rich sequence are often found at sites where all three TFs
      competitively bind.IMPORTANCE Bacteria encounter oxygen fluctuation in their
      natural environment as well as in host organisms. Hence, understanding how
      bacteria respond to oxygen limitation will impact environmental and human health.
      ResD, NsrR, and Fur control transcription under anaerobic conditions. This work
      using in situ DNase I footprinting uncovered the genome-wide binding profile of
      the three transcription factors (TFs). Binding of the TFs is often competitive or
      cooperative depending on the promoters and the presence of other TFs, indicating
      that transcriptional regulation by multiple TFs is much more complex than we
      originally thought. The results from this study provide a more complete picture
      of anaerobic gene regulation governed by ResD, NsrR, and Fur and contribute to
      our further understanding of anaerobic physiology.

PMID- 28439034
TI  - Teleosts as Model Organisms To Understand Host-Microbe Interactions.
AB  - Host-microbe interactions are influenced by complex host genetics and
      environment. Studies across animal taxa have aided our understanding of how
      intestinal microbiota influence vertebrate development, disease, and physiology.
      However, traditional mammalian studies can be limited by the use of isogenic
      strains, husbandry constraints that result in small sample sizes and limited
      statistical power, reliance on indirect characterization of gut microbial
      communities from fecal samples, and concerns of whether observations in
      artificial conditions are actually reflective of what occurs in the wild. Fish
      models are able to overcome many of these limitations. The extensive variation in
      the physiology, ecology, and natural history of fish enriches studies of the
      evolution and ecology of host-microbe interactions. They share physiological and
      immunological features common among vertebrates, including humans, and harbor
      complex gut microbiota, which allows identification of the mechanisms driving
      microbial community assembly. Their accelerated life cycles and large clutch
      sizes and the ease of sampling both internal and external microbial communities
      make them particularly well suited for robust statistical studies of microbial
      diversity. Gnotobiotic techniques, genetic manipulation of the microbiota and
      host, and transparent juveniles enable novel insights into mechanisms underlying
      development of the digestive tract and disease states. Many diseases involve a
      complex combination of genes which are difficult to manipulate in homogeneous
      model organisms. By taking advantage of the natural genetic variation found in
      wild fish populations, as well as of the availability of powerful genetic tools,
      future studies should be able to identify conserved genes and pathways that
      contribute to human genetic diseases characterized by dysbiosis.

PMID- 28439036
TI  - Reclassification of the Specialized Metabolite Producer Pseudomonas
      mesoacidophila ATCC 31433 as a Member of the Burkholderia cepacia Complex.
AB  - Pseudomonas mesoacidophila ATCC 31433 is a Gram-negative bacterium, first
      isolated from Japanese soil samples, that produces the monobactam isosulfazecin
      and the beta-lactam-potentiating bulgecins. To characterize the biosynthetic
      potential of P. mesoacidophila ATCC 31433, its complete genome was determined
      using single-molecule real-time DNA sequence analysis. The 7.8-Mb genome
      comprised four replicons, three chromosomal (each encoding rRNA) and one plasmid.
      Phylogenetic analysis demonstrated that P. mesoacidophila ATCC 31433 was
      misclassified at the time of its deposition and is a member of the Burkholderia
      cepacia complex, most closely related to Burkholderia ubonensis The sequenced
      genome shows considerable additional biosynthetic potential; known gene clusters
      for malleilactone, ornibactin, isosulfazecin, alkylhydroxyquinoline, and
      pyrrolnitrin biosynthesis and several uncharacterized biosynthetic gene clusters
      for polyketides, nonribosomal peptides, and other metabolites were identified.
      Furthermore, P. mesoacidophila ATCC 31433 harbors many genes associated with
      environmental resilience and antibiotic resistance and was resistant to a range
      of antibiotics and metal ions. In summary, this bioactive strain should be
      designated B. cepacia complex strain ATCC 31433, pending further detailed
      taxonomic characterization.IMPORTANCE This work reports the complete genome
      sequence of Pseudomonas mesoacidophila ATCC 31433, a known producer of bioactive
      compounds. Large numbers of both known and novel biosynthetic gene clusters were
      identified, indicating that P. mesoacidophila ATCC 31433 is an untapped resource
      for discovery of novel bioactive compounds. Phylogenetic analysis demonstrated
      that P. mesoacidophila ATCC 31433 is in fact a member of the Burkholderia cepacia
      complex, most closely related to the species Burkholderia ubonensis Further
      investigation of the classification and biosynthetic potential of P.
      mesoacidophila ATCC 31433 is warranted.

PMID- 28439035
TI  - Regulation, Function, and Detection of Protein Acetylation in Bacteria.
AB  - Nepsilon-Lysine acetylation is now recognized as an abundant posttranslational
      modification (PTM) that influences many essential biological pathways.
      Advancements in mass spectrometry-based proteomics have led to the discovery that
      bacteria contain hundreds of acetylated proteins, contrary to the prior notion of
      acetylation events being rare in bacteria. Although the mechanisms that regulate
      protein acetylation are still not fully defined, it is understood that this
      modification is finely tuned via both enzymatic and nonenzymatic mechanisms. The
      opposing actions of Gcn5-related N-acetyltransferases (GNATs) and deacetylases,
      including sirtuins, provide the enzymatic control of lysine acetylation. A
      nonenzymatic mechanism of acetylation has also been demonstrated and proven to be
      prominent in bacteria, as well as in mitochondria. The functional consequences of
      the vast majority of the identified acetylation sites remain unknown. From
      studies in mammalian systems, acetylation of critical lysine residues was shown
      to impact protein function by altering its structure, subcellular localization,
      and interactions. It is becoming apparent that the same diversity of functions
      can be found in bacteria. Here, we review current knowledge of the mechanisms and
      the functional consequences of acetylation in bacteria. Additionally, we discuss
      the methods available for detecting acetylation sites, including quantitative
      mass spectrometry-based methods, which promise to promote this field of research.
      We conclude with possible future directions and broader implications of the study
      of protein acetylation in bacteria.

PMID- 28439037
TI  - Regulation of a Glycerol-Induced Quinoprotein Alcohol Dehydrogenase by sigma54
      and a LuxR-Type Regulator in Azospirillum brasilense Sp7.
AB  - Azospirillum brasilense Sp7 uses glycerol as a carbon source for growth and
      nitrogen fixation. When grown in medium containing glycerol as a source of
      carbon, it upregulates the expression of a protein which was identified as
      quinoprotein alcohol dehydrogenase (ExaA). Inactivation of exaA adversely affects
      the growth of A. brasilense on glycerol. A determination of the transcription
      start site of exaA revealed an RpoN-dependent -12/-24 promoter consensus. The
      expression of an exaA::lacZ fusion was induced maximally by glycerol and was
      dependent on sigma54 Bioinformatic analysis of the sequence flanking the -12/-24
      promoter revealed a 17-bp sequence motif with a dyad symmetry of 6 nucleotides
      upstream of the promoter, the disruption of which caused a drastic reduction in
      promoter activity. The electrophoretic mobility of a DNA fragment containing the
      17-bp sequence motif was retarded by purified EraR, a LuxR-type transcription
      regulator that is transcribed divergently from exaA EraR also showed a positive
      interaction with RpoN in two-hybrid and pulldown assays.IMPORTANCE Quinoprotein
      alcohol dehydrogenase (ExaA) plays an important role in the catabolism of
      alcohols in bacteria. Although exaA expression is thought to be regulated by a
      two-component system consisting of EraS and EraR, the mechanism of regulation was
      not known. This study shows the details of the regulation of expression of the
      exaA gene in A. brasilense We have shown here that exaA of A. brasilense is
      maximally induced by glycerol and harbors a sigma54-dependent promoter. The
      response regulator EraR binds to an inverted repeat located upstream of the exaA
      promoter. This study shows that a LuxR-type response regulator (EraR) binds
      upstream of the exaA gene and physically interacts with sigma54 The unique
      feature of this regulation is that EraR is a LuxR-type transcription regulator
      that lacks the GAFTGA motif, a characteristic feature of the enhancer binding
      proteins that are known to interact with sigma54 in other bacteria.

PMID- 28439038
TI  - Pseudomonas aeruginosa-Derived Rhamnolipids and Other Detergents Modulate Colony
      Morphotype and Motility in the Burkholderia cepacia Complex.
AB  - Competitive interactions mediated by released chemicals (e.g., toxins) are
      prominent in multispecies communities, but the effects of these chemicals at
      subinhibitory concentrations on susceptible bacteria are poorly understood.
      Although Pseudomonas aeruginosa and species of the Burkholderia cepacia complex
      (Bcc) can exist together as a coinfection in cystic fibrosis airways, P.
      aeruginosa toxins can kill Bcc species in vitro Consequently, these bacteria
      become an ideal in vitro model system to study the impact of sublethal levels of
      toxins on the biology of typical susceptible bacteria, such as the Bcc, when
      exposed to P. aeruginosa toxins. Using P. aeruginosa spent medium as a source of
      toxins, we showed that a small window of subinhibitory concentrations modulated
      the colony morphotype and swarming motility of some but not all tested Bcc
      strains, for which rhamnolipids were identified as the active molecule. Using a
      random transposon mutagenesis approach, we identified several genes required by
      the Bcc to respond to low concentrations of rhamnolipids and consequently affect
      the ability of this microbe to change its morphotype and swarm over surfaces.
      Among those genes identified were those coding for type IVb-Tad pili, which are
      often required for virulence in various bacterial pathogens. Our study
      demonstrates that manipulating chemical gradients in vitro can lead to the
      identification of bacterial behaviors relevant to polymicrobial
      infections.IMPORTANCE Interspecies interactions can have profound effects on the
      development and outcomes of polymicrobial infections. Consequently, improving the
      molecular understanding of these interactions could provide us with new insights
      on the possible long-term consequences of these chronic infections. In this
      study, we show that P. aeruginosa-derived rhamnolipids, which participate in Bcc
      killing at high concentrations, can also trigger biological responses in
      Burkholderia spp. at low concentrations. The modulation of potential virulence
      phenotypes in the Bcc by P. aeruginosa suggests that these interactions
      contribute to pathogenesis and disease severity in the context of polymicrobial
      infections.

PMID- 28439039
TI  - InvS Coordinates Expression of PrgH and FimZ and Is Required for Invasion of
      Epithelial Cells by Salmonella enterica serovar Typhimurium.
AB  - Deep sequencing has revolutionized our understanding of the bacterial RNA world
      and has facilitated the identification of 280 small RNAs (sRNAs) in Salmonella
      Despite the suspicions that sRNAs may play important roles in Salmonella
      pathogenesis, the functions of most sRNAs remain unknown. To advance our
      understanding of RNA biology in Salmonella virulence, we searched for sRNAs
      required for bacterial invasion into nonphagocytic cells. After screening 75
      sRNAs, we discovered that the ablation of InvS caused a significant decrease of
      Salmonella invasion into epithelial cells. A proteomic analysis showed that InvS
      modulated the levels of several type III secreted Salmonella proteins. The level
      of PrgH, a type III secretion apparatus protein, was significantly lower in the
      absence of InvS, consistent with the known roles of PrgH in effector secretion
      and bacterial invasion. We discovered that InvS modulates fimZ expression and
      hence flagellar gene expression and motility. We propose that InvS coordinates
      the increase of PrgH and decrease in FimZ that promote efficient Salmonella
      invasion into nonphagocytic cells.IMPORTANCE Salmonellosis continues to be the
      most common foodborne infection reported by the CDC in the United States. Central
      to Salmonella pathogenesis is the ability to invade nonphagocytic cells and to
      replicate inside host cells. Invasion genes are known to be regulated by protein
      transcriptional networks, but little is known about the role played by small RNAs
      (sRNAs) in this process. We have identified a novel sRNA, InvS, that is involved
      in Salmonella invasion. Our result will likely provide an opportunity to better
      understand the fundamental question of how Salmonella regulates invasion gene
      expression and may inform strategies for therapeutic intervention.

PMID- 28439041
TI  - Cues from the Membrane: Bacterial Glycerophospholipids.
AB  - In this issue of the Journal of Bacteriology, V. W. Rowlett et al. unveil new
      Escherichia coli circuitry linking membrane glycerophospholipid (GPL) homeostasis
      to bacterial stress response and adaptation mechanisms (J Bacteriol 199:e00849
      16, 2017, https://doi.org/10.1128/JB.00849-16). Glycerophospholipids comprise
      critical components of the dual-membrane envelope of Gram-negative bacteria and
      participate in many processes. The new evidence suggests that, in some instances,
      distinct E. coli GPL molecules function for distinct biochemistry and bacteria
      sense perturbations in membrane GPL concentrations to coordinate survival
      strategies. Understanding GPL sensing and remodeling mechanisms will be important
      moving forward, given the breadth of function for these molecules in
      bacteriology.

PMID- 28439040
TI  - Impact of Membrane Phospholipid Alterations in Escherichia coli on Cellular
      Function and Bacterial Stress Adaptation.
AB  - Bacteria have evolved multiple strategies to sense and rapidly adapt to
      challenging and ever-changing environmental conditions. The ability to alter
      membrane lipid composition, a key component of the cellular envelope, is crucial
      for bacterial survival and adaptation in response to environmental stress.
      However, the precise roles played by membrane phospholipids in bacterial
      physiology and stress adaptation are not fully elucidated. The goal of this study
      was to define the role of membrane phospholipids in adaptation to stress and
      maintenance of bacterial cell fitness. By using genetically modified strains in
      which the membrane phospholipid composition can be systematically manipulated, we
      show that alterations in major Escherichia coli phospholipids transform these
      cells globally. We found that alterations in phospholipids impair the cellular
      envelope structure and function, the ability to form biofilms, and bacterial
      fitness and cause phospholipid-dependent susceptibility to environmental
      stresses. This study provides an unprecedented view of the structural, signaling,
      and metabolic pathways in which bacterial phospholipids participate, allowing the
      design of new approaches in the investigation of lipid-dependent processes
      involved in bacterial physiology and adaptation.IMPORTANCE In order to cope with
      and adapt to a wide range of environmental conditions, bacteria have to sense and
      quickly respond to fluctuating conditions. In this study, we investigated the
      effects of systematic and controlled alterations in bacterial phospholipids on
      cell shape, physiology, and stress adaptation. We provide new evidence that
      alterations of specific phospholipids in Escherichia coli have detrimental
      effects on cellular shape, envelope integrity, and cell physiology that impair
      biofilm formation, cellular envelope remodeling, and adaptability to
      environmental stresses. These findings hold promise for future antibacterial
      therapies that target bacterial lipid biosynthesis.

PMID- 28439042
TI  - Correction: Analysis and identification of the Grem2 heparin/heparan sulfate
      binding motif.

PMID- 28439044
TI  - Correction to: MicroRNA-17-92 Cluster in Exosomes Enhance Neuroplasticity and
      Functional Recovery After Stroke in Rats.

PMID- 28439045
TI  - Correction to: Successful Reperfusion With Mechanical Thrombectomy Is Associated
      With Reduced Disability and Mortality in Patients With Pretreatment Diffusion
      Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score <=6.

PMID- 28439046
TI  - Protein phosphatase 2A regulatory subunit B55alpha functions in mouse oocyte
      maturation and early embryonic development.
AB  - Protein phosphatase 2A regulatory subunit B55alpha (PP2A-B55alpha) has been
      studied in mitosis. However, its functions in mammalian meiosis and early
      embryonic development remain unknown. Here, we report that PP2A-B55alpha is
      critical for mouse oocyte meiosis and preimplantation embryo development.
      Knockdown of PP2A-B55alpha in oocytes led to abnormal asymmetric division,
      disordered spindle dynamics, defects in chromosome congression, an increase in
      aneuploidy, and induction of the DNA damage response. Moreover, knockdown of PP2A
      B55alpha in fertilized mouse zygotes impaired development to the blastocyst
      stage. The impairment of embryonic development might have been due to induction
      of sustained DNA damage in embryos, which caused apoptosis and inhibited cell
      proliferation and outgrowth potential at the blastocyst stage. Overall, these
      results provide a novel insight into the role of PP2A-B55alpha as a novel meiotic
      and embryonic competence factor at the onset of life.

PMID- 28439048
TI  - Faecal volatile organic compounds analysis using field asymmetric ion mobility
      spectrometry: non-invasive diagnostics in paediatric inflammatory bowel disease.
AB  - BACKGROUND AND OBJECTIVES: Inflammatory bowel disease (IBD), including Crohn's
      disease (CD) and ulcerative colitis (UC), remains challenging to diagnose.
      Diagnostic work-up carries a high burden, especially in paediatric patients, due
      to invasive endoscopic procedures. IBD is associated with alterations in
      intestinal microbiota composition. Faecal volatile organic compounds (VOCs)
      reflect gut microbiota composition. The aim of this study was to assess the
      diagnostic accuracy of faecal VOC profiling as a non-invasive diagnostic
      biomarker for paediatric IBD. METHODS: In this diagnostic accuracy study
      performed in two tertiary centres in the Netherlands, faecal VOC profiles of 36
      de novo, treatment-naive paediatric IBD patients (23 CD, 13 UC), and 24 healthy,
      matched controls were measured by field asymmetric ion mobility spectrometry
      (Owlstone Ltd, Lonestar(r), UK). RESULTS: Faecal VOC profiles of de novo
      paediatric IBD patients could be differentiated from healthy controls (AUC +/-
      95% CI, p-value, sensitivity, specificity; 0.76 +/- 0.14, p < 0.001, 79%, 78%).
      This discrimination from controls was observed in both CD (0.90 +/- 0.10, p <
      0.0001, 83%, 83%) and UC (0.74 +/- 0.19, p = 0.02, 77%, 75%). VOC profiles from
      UC could not be discriminated from CD (0.67 +/- 0.19, p = 0.0996, 65%, 62%).
      CONCLUSION: Field asymmetric ion mobility spectrometry allowed for discrimination
      between faecal VOC profiles of de novo paediatric IBD patients and healthy
      controls, confirming the potential of faecal VOC analysis as a non-invasive
      diagnostic biomarker for paediatric IBD. This method may serve as a
      complementary, non-invasive technique in the diagnosis of IBD, possibly limiting
      the number of endoscopies needed in children suspected for IBD.

PMID- 28439049
TI  - [Calcium and bone metabolism across women's life stages. Epidemiology of bone and
      joint disease in Japanese women.]
AB  - Bone and joint diseases are severe problems in the elderly;therefore, the
      development of their treatment or prophylaxis is quite important. Our study shows
      that the prevalence of osteoporosis and osteoarthritis is very high, and its
      impact on quality of life is strong. The treatment rate of osteoporosis is less
      than 10%, and awareness programs for prevention of osteoporosis and
      osteoarthritis disorders such as locomotive syndrome are needed.

PMID- 28439047
TI  - Functional human GRIN2B promoter polymorphism and variation of mental processing
      speed in older adults.
AB  - We investigated the role of a single nucleotide polymorphism rs3764030 (G>A)
      within the human GRIN2B promoter in mental processing speed in healthy,
      cognitively intact, older adults. In vitro DNA-binding and reporter gene assays
      of different allele combinations in transfected cells showed that the A allele
      was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We
      tested the hypothesis that individuals with A allele will have better memory
      performance (i.e. faster reaction times) in older age. Twenty-eight older adults
      (ages 65-86) from a well-characterized longitudinal cohort were recruited and
      performed a modified delayed match-to-sample task. The rs3764030 polymorphism was
      genotyped and participants were grouped based on the presence of the A allele
      into GG and AA/AG. Carriers of the A allele maintained their speed of memory
      retrieval over age compared to GG carriers (p = 0.026 slope of the regression
      line between AA and AG versus GG groups). To validate the results, 12 older
      adults from the same cohort participated in a different version of the short-term
      memory task. Reaction times were significantly slower with age in older adults
      with G allele (p < 0.001). These findings support a role for rs3764030 in
      maintaining faster mental processing speed over aging.

PMID- 28439050
TI  - [Calcium and bone metabolism across women's life stages. Changes of biochemical
      markers of bone turnover in life cycle of women.]
AB  - Development of bone metabolism markers began about 35 years ago. Current by the
      osteoporosis and bone metabolism diseases diagnosis and treatment efficacy. In
      childhood and adolescence, bone formation and resorption were increased, but
      formation rate was exceeded resorption rate. To keep strength of bone, bone
      formation and resorption are balanced(remodeling)in the period of maturity, Bone
      mineral density greatly decreases and biochemical markers of bone turnover
      markedly increase in postmenopausal women, indicating accelerated bone remodeling
      because of estrogen withdrawal. On the other hand, pregnancy and breastfeeding
      affect bone metabolism. So, we gynecologists should be careful about bone health
      with understanding characteristic of bone metabolism markers.

PMID- 28439051
TI  - [Calcium and bone metabolism across women's life stages. Molecular mechanisms
      underlying bone metabolism by estrogen.]
AB  - Osteoporosis, which patients are estimated as more than 13 million in Japan, is
      mainly caused by postmenopausal osteoporosis. Estrogen deficiency induced by
      menopause can disturb endocrine feedback and homeostasis, followed by bone loss
      by increased bone resorption with high bone turnover. Recent studies using
      systemic or conditional Estrogen Receptor alpha(ERalpha)gene knockout mice have
      unveiled molecular mechanisms underlying bone metabolism. In this review, it will
      be discussed that direct and indirect effects of estrogen and its metabolites for
      bone metabolism.

PMID- 28439052
TI  - [Calcium and bone metabolism across women's life stages. Pathophysiology,
      adiagnosis and treatment of post-pregnancy osteoporosis.]
AB  - Post-pregnancy osteoporosis is a rare condition with little known
      pathophysiology. Most cases are diagnosed in the late stage of pregnancy or in
      the post-partum while breastfeeding, particularly in first pregnancy. Vertebral
      fractures are most commonly observed and characterized by prolonged severe pain
      and functional limitations. Measurements of bone mineral density(BMD)of the
      lumbar spine and proximal femur with dual energy X-ray absorptiometry(DXA)are the
      clinical methods most commonly used for no fracture women. Conventional
      radiography will confirm the fracture in most cases, and magnetic resonance(MR),
      which can be safely used during pregnancy, is effective in detecting vertebral
      fractures and bone marrow edema. Although the bone resorption increased at the
      end of pregnancy and lactation, the bone formation increases and the bone
      structure is almost recovered after cessation of lactating in postpartum. There
      is much uncertainty about whether pharmacological treatments should be used for
      osteoporosis that presents during pregnancy and lactation. This is partly because
      of the lack of a firm evidence base for treatment and also because there is a
      spontaneous recovery of bone mass and strength after pregnancy or weaning.

PMID- 28439053
TI  - [Calcium and bone metabolism across women's life stages. Bone metabolism of women
      in primary amenorrhea.]
AB  - For development of the bone during adolescence, the increased estrogen plays an
      important role especially in young women as well as GH/IGF-I system. Although
      primary amenorrhea can be caused by various pathological factors, almost of cases
      have a dysfunction of estrogen secretory systems. For Turner syndrome, which is
      well-known disease with primary amenorrhea,it is generally recommended that the
      estrogen therapy is started at adolescence and gradually increased up to adult
      dose level. Recently studies about the adequate dose of estrogen and the adequate
      age of adult dose in Turner syndrome revealed that intervention with adult dose
      of estrogen is required as soon as possible for gaining better bone mineral. In
      the point of view for bone fragility at the future, early diagnosis and adequate
      intervention for primary amenorrhea is important.

PMID- 28439054
TI  - [Calcium and bone metabolism across women's life stages. The effects of oral
      contraceptives/low dose estrogen-progestin on bone metabolism, bone mass and
      geometry in adolescent and young adult women.]
AB  - Estrogens have a biphasic action on pubertal and/or adolescent skeletal growth.
      Low levels of estrogen may increase the periosteal expansion through the increase
      in the sensitivity of bone for mechanical stimuli and the secretion of IGF-1. On
      the other hand, high estrogen concentrations may inhibit periosteal bone
      formation. To use OC/LEP(oral contraceptive/low dose estrogen-progestin) during
      adolescence, meaning exposure to high levels of estrogen, may prevent the
      acquisition of physiologic peak of bone mass.

PMID- 28439055
TI  - [Calcium and bone metabolism across women's life stages. Bone metabolism and
      estrogen/androgen balance in women.]
AB  - Androgen as well as estrogen has physical, psychological and sexual roles in
      women. The action of androgen on bone health in women is important. The androgen
      receptor is expressed in osteoblasts and osteocytes but the mechanism has not
      been clarified in women. It has been reported that endogenous testosterone level
      was positively correlated with bone mineral density and higher testosterone level
      might be associated with decrease in bone fractures. Also, it has been reported
      that bone mineral density in women who received testosterone with estrogen was
      higher than that in women who received estrogen alone. However, it is important
      to pay attention to occur adverse effects such as hirsutism, acne, disorder of
      liver function and dyslipidemia. In addition, occurrence of breast cancer and
      endometrial cancer should be considered. In postmenopausal women, appropriate
      range of circulating testosterone level may play favor roles in various tissues.

PMID- 28439056
TI  - [Calcium and bone metabolism across women's life stages. Treatment for the
      malignant tumors in women and bone calcium metabolism.]
AB  - In the malignant tumors in women, uterine cervical cancer, endometrial cancer,
      ovarian cancer, and breast cancer are representative diseases. The cancer
      treatment is classified roughly into an operation, medical treatment, and
      radiation therapy and has an extremely big influence on ovarian function. With
      the improvement in survival of cancer patients, the importance of the health care
      for the cancer survivors increases. It is necessary to prevent the onset of the
      osteoporotic fractures to maintain QOL. This paper describes the action that the
      malignant tumors of the women affect bone metabolism mainly from the viewpoint of
      ovarian function.

PMID- 28439057
TI  - [Calcium and bone metabolism across women's life stages. Osteoporosis in female
      patients with rheumatoid arthritis.]
AB  - Female patients with rheumatoid arthritis(RA)are at high risk for osteoporosis
      and fractures. In Japanese female patients with RA, age, disability, daily
      prednisolone dose, history of total knee replacement, and low bone mineral
      density are known to be risk factors for fractures, and more than 70% are
      reported to be vitamin D deficiency.

PMID- 28439058
TI  - [Calcium and bone metabolism across women's life stages. Stress fracture in
      female athletes.]
AB  - Stress fractures are common overuse injuries in athletes, especially in long
      distance runner, jumping sports and gymnastics in female athletes. The pathology
      of stress fracture mainly includes repeated biomechanical loading, which leads to
      bone micro-damage and failure of bone structure. Female athlete triad(FAT), which
      includes low energy availability with or without an eating disorder, functional
      hypothalamic amenorrhea, and osteoporosis, is a serious healthcare concern in
      female athletes. For prevention and treatment of stress fracture, management of
      biomechanical factors modifying the load applied to a bone is important, and
      especially in female athletes, management for FAT is one of the important
      factors. This report outlines the current knowledge on the epidemiology,
      diagnosis, treatment and prevention of stress fracture, relating to FAT in female
      athletes.

PMID- 28439059
TI  - [Calcium and bone metabolism across women's life stages. Nutritive therapy for
      improvement of bone and calcium metabolism according to life stage in women.]
AB  - Postmenopausal osteoporosis is mainly caused by decreased estrogen levels, and
      progression of disease is associated with irreversible changes. It is therefore
      extremely important to maintain or improve healthy bone and calcium metabolism
      during and before the climacteric from a preventive medicine viewpoint. The
      specific preventive measures are appropriate calcium intake and regular physical
      exercise. In recent years, women in their twenties are considerably thinner and
      have a lower calcium intake than women in other age groups, which may lead to a
      further increase in the number of women with osteoporosis in the future. From the
      aspect of female hormone secretion, women are at higher risk for osteoporosis
      than men at any given age. Aggressive intervention should therefore be undertaken
      to prevent osteoporosis according to life stage in women.

PMID- 28439060
TI  - [Calcium and bone metabolism across women's life stages. Exercise and sport to
      increase bone strength in accordance with female lifecycle.]
AB  - Among females who require the strategies for preventing osteoporosis, appropriate
      exercise and sport through all their life are important to increase or maintain
      bone mass. However, the type of exercise and sport applied to females is
      different in accordance with the lifecycle. Jumping exercise increases bone
      mineral content(BMC)in prepubescent children(premenarcheal girls). Bone mineral
      density(BMD)is higher in adolescent athletes who are engaged in weight-bearing
      activities. Jumping exercise, muscle strengthening exercise, and weight-bearing
      plus muscle strengthening exercises increase BMD in young adults and
      premenopausal women. Walking, aerobic weight-bearing exercise, muscle
      strengthening exercise, and weight-bearing plus muscle strengthening exercises
      maintain or increase BMD in postmenopausal women. Thus, appropriate exercise and
      sport in accordance with the lifecycle are important strategies for preventing
      osteoporosis in females.

PMID- 28439061
TI  - [Calcium and bone metabolism across women's life stages. Bone quality and
      treatment of osteoporosis by SERM.]
AB  - Estrogen deficiency induces bone resorption and bone collagen crosslink
      abnormalities such as reductions in enzymatic cross-links and accumulation of
      Advanced glycation end products(AGEs). In this review, we described that the
      mechanism of poor bone quality in estrogen deficiency and how selective estrogen
      receptor modulators such as raloxifene and bazedoxifene improve bone structural
      and material properties.

PMID- 28439062
TI  - A Rare Case of Necrotizing Myopathy and Fibrinous and Organizing Pneumonia with
      Anti-EJ Antisynthetase Syndrome and SSA Antibodies.
AB  - BACKGROUND Idiopathic inflammatory myopathies are autoimmune disorders that can
      involve the skin, joints, muscles, and lungs. The most common of these disorders
      are dermatomyositis, polymyositis, overlap syndrome, and inclusion body myositis.
      Necrotizing autoimmune myopathy is an idiopathic inflammatory myopathy that is
      rarely associated with Sjogren's syndrome. The most common lung findings
      associated with anti-EJ antisynthetase syndrome are nonspecific interstitial
      pneumonia and usual interstitial pneumonia; this condition is rarely associated
      with fibrinous and organizing pneumonia. CASE REPORT Here, we present a rare case
      of necrotizing myopathy and fibrinous and organizing pneumonia in a 34-year-old
      African American man with Sjogren's syndrome and anti-EJ antibodies. The
      patient's presenting symptoms were cough and proximal muscle weakness of the
      extremities. He had elevated serum creatine kinase level, aldolase level, and
      erythrocyte sedimentation rate. Myositis panel was positive for anti-EJ
      antibodies. Chest radiography was consistent with bilateral interstitial
      infiltrates. CT chest showed patchy bilateral infiltrates. Quadriceps muscle
      biopsy revealed widespread necrotic fibers and lung biopsy showed fibrinous and
      organizing pneumonia. The patient responded well to immunoglobulin therapy,
      mycophenolate, and prednisone, which resulted in complete resolution of bilateral
      infiltrates and improved muscle pain and weakness. CONCLUSIONS Myopathies are
      characterized by myalgia and muscle weakness due to muscle fiber dysfunction and
      are associated with autoimmune diseases. Histopathological features may differ in
      idiopathic inflammatory myopathies. It is important to recognize the rare
      association of anti-EJ autoantibodies with necrotizing myopathy and interstitial
      lung disease, which responds well to methylprednisolone and intravenous
      immunoglobulin.

PMID- 28439063
TI  - Liver Transplantation Outcomes in Recipients with High Model for End-Stage Liver
      Disease (MELD) Scores: The Relevance of MELD Scores.
AB  - BACKGROUND The aim of this study was to assess risk factors for postoperative
      mortality after liver transplantation among patients with Model for End-Stage
      Liver Disease (MELD) scores >=35, with special focus on the MELD scores. MATERIAL
      AND METHODS Data from 68 primary liver transplantations in patients with MELD
      scores >=35 among 1376 liver transplantations performed in the Department of
      General, Transplant, and Liver Surgery (Medical University of Warsaw) between
      January 2002 and October 2014 were analyzed retrospectively. Postoperative (90
      day) mortality was set as the primary outcome measure. RESULTS Postoperative
      mortality was 29.4% (20 of 68). The overall survival rates after 1, 5, and 10
      years were 61.9%, 59.7%, and 59.7%, respectively. According to univariate
      analyses, MELD (p=0.014), conventional technique of liver transplantation
      (p=0.049), intraoperative fresh frozen plasma (p=0.040), and red blood cells
      (p=0.026) transfusions were risk factors for postoperative mortality. MELD score
      was the only independent risk factor for postoperative mortality (p=0.023) in
      multivariate analysis. According to receiver operating characteristics analysis,
      the optimal cut-off for MELD score in prediction of postoperative mortality was
      >=43 (Area Under Curve=0.703, 95% Confidence Interval 0.575-0.831). Postoperative
      mortality was 21.4% and 42.3% among patients with MELD score <43 and >=43,
      respectively (p=0.066). CONCLUSIONS MELD score is an important predictor of early
      mortality after liver transplantation, even among recipients with high MELD
      scores. In particular, patients with MELD score >=43 should be considered as very
      high-risk candidates for liver transplantation.

PMID- 28439064
TI  - Immunotherapy of Dual-Function Vector with Both Immunostimulatory and B-Cell
      Lymphoma 2 (Bcl-2)-Silencing Effects on Gastric Carcinoma.
AB  - BACKGROUND Tumorigenesis is a kind of pathology marked by infinite proliferation
      and restrained apoptosis compared with normal cells. The abnormal expression of
      some proto-oncogenes and apoptosis inhibition are essential for tumor growth,
      which has been confirmed by molecular biologic and immunologic studies. The
      hypofunction of the host immune system also drives the development and metastasis
      of malignant tumors. Bcl-2, which has a critical role in regulating apoptosis, is
      overexpressed in several cancers. MATERIAL AND METHODS In this study, we
      constructed a dual-function small hairpin RNA (shRNA) vector containing an Bcl-2
      silencing shRNA and a TLR7-stimulating ssRNA and examined it effect on tumor cell
      growth and proliferation. RESULTS Stimulation with this bi-functional vector in
      vitro promoted significant apoptosis of MFC cells by regulating the expression of
      apoptosis-related proteins and induced secretion of type I IFNs. Most
      importantly, this bi-functional vector more effectively inhibited subcutaneous
      MFC cell growth than did single shRNA and ssRNA treatment in vivo. Natural killer
      (NK) and CD4+ T cells were required for effective tumor suppression, and TLR7 was
      shown to play a helper role in the activation of NK cells and CD4+ T cells,
      possibly by regulating the expression of receptors or secretion of cytokines.
      CONCLUSIONS This bi-functional vector that contained ssRNA and shRNA may
      represent a promising approach for tumor therapy.

PMID- 28439065
TI  - Multidisciplinary study of the secondary immune response in grandparents re
      exposed to chickenpox.
AB  - Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the
      elderly. This secondary immune response is hypothesized to confer protection
      against herpes zoster. We longitudinally sampled 36 adults over the course of one
      year after re-exposure to chickenpox. The resulting 183 samples and those of 14
      controls were assessed for VZV-specific T-cell immunity and antibody titres. The
      percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in re
      exposed grandparents compared to control participants up to 9 months after re
      exposure. Using a longitudinal mixture modelling approach, we found that 25% and
      17% of re-exposed grandparents showed a boosting of VZV-specific CD4+ IL-2
      producing T-cells and VZV-specific antibodies, respectively. The antibody
      boosting occurred exclusively in cytomegalovirus (CMV) IgG-positive participants.
      CMV IgG-positive participants also had higher VZV IE62-specific CD4+ IFN-gamma
      producing T-cell percentages and VZV-specific antibody titres. The protective
      effect of re-exposure to chickenpox is likely limited, as boosting only occurred
      in 17-25% of the VZV re-exposed grandparents and for less than one year.

PMID- 28439066
TI  - Silicon amendment to rice plants impairs sucking behaviors and population growth
      in the phloem feeder Nilaparvata lugens (Hemiptera: Delphacidae).
AB  - The brown planthopper (BPH), Nilaparvata lugens (Stal), is a migratory and
      destructive sucking insect pest of rice. Silicon (Si) amendment to plants can
      confer enhanced resistance to herbivores and is emerging as a novel approach for
      pest management. In the present study, we tested the effects of Si addition at
      0.16 (low) and 0.32 (high) g Si/kg soil on sucking behaviors and population
      growth in BPH. Si amendment increased Si content in rice stems and extended non
      probing event and phloem puncture followed by sustained phloem ingestion over
      that in the no-Si-addition control. High Si addition rate prolonged the stylet
      pathway and the time needed to reach the first phloem puncture, shortened
      durations of phloem puncture and phloem ingestion, and decreased the proportion
      of individuals that produced sustained phloem ingestion. BPH female feeding on
      and preference for plants with the high Si addition rate were also reduced. As a
      result, Si application significantly decreased BPH population growth rates while
      increased population doubling time. These results indicate that Si amendment,
      especially at the high rate, confers enhanced rice plant resistance to BPH
      through impairment of BPH feeding. Our results highlight the potential of Si
      amendment as an alternative for BPH management.

PMID- 28439068
TI  - Limited genomic consequences of hybridization between two African clawed frogs,
      Xenopus gilli and X. laevis (Anura: Pipidae).
AB  - The Cape platanna, Xenopus gilli, an endangered frog, hybridizes with the African
      clawed frog, X. laevis, in South Africa. Estimates of the extent of gene flow
      between these species range from pervasive to rare. Efforts have been made in the
      last 30 years to minimize hybridization between these two species in the west
      population of X. gilli, but not the east populations. To further explore the
      impact of hybridization and the efforts to minimize it, we examined molecular
      variation in one mitochondrial and 13 nuclear genes in genetic samples collected
      recently (2013) and also over two decades ago (1994). Despite the presence of F 1
      hybrids, none of the genomic regions we surveyed had evidence of gene flow
      between these species, indicating a lack of extensive introgression. Additionally
      we found no significant effect of sampling time on genetic diversity of
      populations of each species. Thus, we speculate that F 1 hybrids have low fitness
      and are not backcrossing with the parental species to an appreciable degree.
      Within X. gilli, evidence for gene flow was recovered between eastern and western
      populations, a finding that has implications for conservation management of this
      species and its threatened habitat.

PMID- 28439069
TI  - Drying-mediated patterns in colloid-polymer suspensions.
AB  - Drying-mediated patterning of colloidal particles is a physical phenomenon that
      must be understood in inkjet printing technology to obtain crack-free uniform
      colloidal films. Here we experimentally study the drying-mediated patterns of a
      model colloid-polymer suspension and specifically observe how the deposit pattern
      appears after droplet evaporation by varying particle size and polymer
      concentration. We find that at a high polymer concentration, the ring-like
      pattern appears in suspensions with large colloids, contrary to suppression of
      ring formation in suspensions with small colloids thanks to colloid-polymer
      interactions. We attribute this unexpected reversal behavior to hydrodynamics and
      size dependence of colloid-polymer interactions. This finding would be very
      useful in developing control of drying-mediated self-assembly to produce crack
      free uniform patterns from colloidal fluids.

PMID- 28439067
TI  - Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption
      of F-actin and microtubule organization is mediated by Akt1/2.
AB  - PFOS (perfluorooctanesulfonate, or perfluorooctane sulfonic acid) is an
      anthropogenic fluorosurfactant widely used in consumer products. While its use in
      Europe, Canada and the U.S. has been banned due to its human toxicity, it
      continues to be used in China and other developing countries as a global
      pollutant. Herein, using an in vitro model of Sertoli cell blood-testis barrier
      (BTB), PFOS was found to induce Sertoli cell injury by perturbing actin
      cytoskeleton through changes in the spatial expression of actin regulatory
      proteins. Specifically, PFOS caused mis-localization of Arp3 (actin-related
      protein 3, a branched actin polymerization protein) and palladin (an actin
      bundling protein). These disruptive changes thus led to a dis-organization of F
      actin across Sertoli cell cytosol, causing truncation of actin microfilament,
      thereby failing to support the Sertoli cell morphology and adhesion protein
      complexes (e.g., occludin-ZO-1, CAR-ZO-1, and N-cadherin-beta-catenin), through a
      down-regulation of p-Akt1-S473 and p-Akt2-S474. The use of SC79, an Akt1/2
      inhibitor, was found to block the PFOS-induced Sertoli cell injury by rescuing
      the PFOS-induced F-actin dis-organization. These findings thus illustrate PFOS
      exerts its disruptive effects on Sertoli cell function downstream through Akt1/2.
      As such, PFOS-induced male reproductive dysfunction can possibly be managed
      through an intervention on Akt1/2 expression.

PMID- 28439071
TI  - Diabetes mellitus and the risk of multidrug resistant tuberculosis: a meta
      analysis.
AB  - The high prevalence of diabetes mellitus (DM) among multidrug resistant
      tuberculosis (MDR-TB) patients is a serious cause for concern. We conducted a
      meta-analysis to determine whether DM is an independent risk factor for MDR-TB.
      Electronic literature searches of the PubMed, Web of Science and EMBASE databases
      up to July 12, 2016 were conducted. The pooled adjusted odds ratio (OR) and 95%
      confidence intervals (CIs) were calculated using the random effects model with
      STATA 12.0 software. In total 13 studies, including 9289 individuals with TB,
      were included in this meta-analysis. Significant association between DM and MDR
      TB (OR = 1.71; 95% CI = 1.32, 2.22) was identified. Subgroup analyses showed
      that: 1) Pooled OR was 1.25 (95% CI: 0.82-1.91) for cross-sectional studies, and
      was 2.14 (95% CI: 1.51-3.02) for longitudinal studies; 2) The pooled OR was 1.69
      (95% CI:1.09-2.62) for primary MDR-TB, 1.94 (95% CI:1.42-2.65) for any MDR-TB,
      and 0.85 for secondary MDR-TB (95% CI: 0.29-2.54); 3) DM was significantly
      associated with MDR-TB in both Caucasian (OR = 2.26, 95% CI: 1.66-3.07) and Asian
      (OR = 1.40, 95% CI: 1.01-1.95) subgroups. No evidence of publication bias was
      identified. In conclusion, the pooling analysis indicated that DM was an
      independent risk factor for MDR-TB, especially for primary MDR-TB.

PMID- 28439070
TI  - Clinical and microbiological characteristics, and impact of therapeutic
      strategies on the outcomes of children with candidemia.
AB  - We aimed to determine the clinical and microbiological characteristics of Candida
      bloodstream infections in children and the impact of therapeutic strategies on
      outcomes. All pediatric patients with candidemia from a medical center in Taiwan
      over a 13-year period (2003-2015) were included and a total of 262 patients with
      319 episodes of candidemia were analyzed. Overall susceptibility to fluconazole
      was 86.1%. Cumulative mortality at 7 and 30 days after the first episode of
      candidemia was 13.4% and 25.2%, respectively. The overall in-hospital mortality
      rate was 35.1%. The treatment outcomes did not change over the study period.
      Multivariate analysis showed that delayed catheter removal (odds ratio [OR],
      5.52; 95% confidence interval [CI]: 2.97-10.25), septic shock (OR, 5.49; 95% CI:
      2.85-10.57), and breakthrough candidemia (OR, 3.66; 95% CI: 1.43-9.35) were
      independently associated with clinical treatment failure. In children with
      candidemia, underlying renal insufficiency and hematological/oncological
      malignancy, delayed catheter removal, and septic shock at onset were
      independently associated final in-hospital mortality. Analyzing the subgroup of
      non-neonatal children did not change the findings. We concluded overall mortality
      of pediatric candidemia remains high during the past decade. Prompt early
      catheter removal and aggressive treatment strategy in patients with septic shock
      would be critical to improve outcomes.

PMID- 28439072
TI  - Fecal microbial characterization of hospitalized patients with suspected
      infectious diarrhea shows significant dysbiosis.
AB  - Hospitalized patients are at increased risk for acquiring healthcare-associated
      infections (HAIs) and inadequate nutrition. The human intestinal microbiota plays
      vital functions in nutrient supply and protection from pathogens, yet
      characterization of the microbiota of hospitalized patients is lacking. We used
      16S rRNA amplicon sequencing to characterize the global pattern of microbial
      composition of fecal samples from 196 hospitalized patients with suspected
      infectious diarrhea in comparison to healthy, non-hospitalized subjects (n =
      881), and to traditional culture results. We show that hospitalized patients have
      a significant rise in alpha-diversity (richness within sample) from birth to <4
      years of age, which continues up to the second decade of life. Additionally, we
      noted a profoundly significant increase in taxa from Proteobacteria phylum in
      comparison to healthy subjects. Finally, although more than 60% of hospitalized
      samples had a greater than 10% abundance of Proteobacteria, there were only
      19/196 (10%) positive cultures for Campylobacter, Salmonella, or Shigella entero
      pathogens in traditional culturing methods. As hospitalized patients have
      increased risk for HAIs and inadequate nutrition, our data support the
      consideration of nutritional and/or microbial modification in this population.

PMID- 28439074
TI  - How to test for partially predictable chaos.
AB  - For a chaotic system pairs of initially close-by trajectories become eventually
      fully uncorrelated on the attracting set. This process of decorrelation can split
      into an initial exponential decrease and a subsequent diffusive process on the
      chaotic attractor causing the final loss of predictability. Both processes can be
      either of the same or of very different time scales. In the latter case the two
      trajectories linger within a finite but small distance (with respect to the
      overall extent of the attractor) for exceedingly long times and remain partially
      predictable. Standard tests for chaos widely use inter-orbital correlations as an
      indicator. However, testing partially predictable chaos yields mostly ambiguous
      results, as this type of chaos is characterized by attractors of fractally
      broadened braids. For a resolution we introduce a novel 0-1 indicator for chaos
      based on the cross-distance scaling of pairs of initially close trajectories.
      This test robustly discriminates chaos, including partially predictable chaos,
      from laminar flow. Additionally using the finite time cross-correlation of pairs
      of initially close trajectories, we are able to identify laminar flow as well as
      strong and partially predictable chaos in a 0-1 manner solely from the properties
      of pairs of trajectories.

PMID- 28439073
TI  - In vitro developmental ability of ovine oocytes following intracytoplasmic
      injection with freeze-dried spermatozoa.
AB  - Freeze-drying (FD) is a new and alternative method to preserve spermatozoa in
      refrigeration or at room temperature. Suitable protection is required to maintain
      the sperm DNA integrity during the whole process and storage. The aim of this
      study was to examine the effect of rosmarinic acid and storage temperature on the
      DNA integrity of freeze-dried ram sperm. In addition, we evaluated the in vitro
      developmental ability to the blastocyst stage of oocytes injected with freeze
      dried sperm. Ram sperm was freeze-dried in basic medium and in this medium
      supplemented with 105 uM rosmarinic acid. The vials were stored for 1 year at 4 
      degrees C and at room temperature. Frozen sperm was used as control. After
      rehydration, sperm DNA damage was evaluated, observing that the percentage of
      spermatozoa with DNA damage decreased significantly in the presence of rosmarinic
      acid, without differences between the two storage temperatures. Moreover, no
      differences were observed between the freeze-dried group and the frozen-thawed
      group in terms of blastocyst formation rate. We proved for the first time that
      ovine spermatozoa can be lyophilized effectively, stored at room temperature for
      long term, reconstituted and further injected into oocytes with initial embryo
      development.

PMID- 28439075
TI  - Switch from ambient to focal processing mode explains the dynamics of free
      viewing eye movements.
AB  - Previous studies have reported that humans employ ambient and focal modes of
      visual exploration while they freely view natural scenes. These two modes have
      been characterized based on eye movement parameters such as saccade amplitude and
      fixation duration, but not by any visual features of the viewed scenes. Here we
      propose a new characterization of eye movements during free viewing based on how
      eyes are moved from and to objects in a visual scene. We applied this
      characterization to data obtained from freely-viewing macaque monkeys. We show
      that the analysis based on this characterization gives a direct indication of a
      behavioral shift from ambient to focal processing mode along the course of free
      viewing exploration. We further propose a stochastic model of saccade sequence
      generation incorporating a switch between the two processing modes, which
      quantitatively reproduces the behavioral features observed in the data.

PMID- 28439076
TI  - Practice makes perfect: self-reported adherence a positive marker of inhaler
      technique maintenance.
AB  - : Poor inhaler technique and non-adherence to treatment are major problems in the
      management of asthma. Patients can be taught how to achieve good inhaler
      technique, however maintenance remains problematic, with 50% of patients unable
      to demonstrate correct technique. The aim of this study was to determine the
      clinical, patient-related and/or device-related factors that predict inhaler
      technique maintenance. Data from a quality-controlled longitudinal community care
      dataset was utilized. 238 patients using preventer medications where included.
      Data consisted of patient demographics, clinical data, medication-related factors
      and patient-reported outcomes. Mixed effects logistic regression was used to
      identify predictors of inhaler technique maintenance at 1 month. The variables
      found to be independently associated with inhaler technique maintenance using
      logistic regression (Chi 2 (3,n = 238) = 33.24, p < 0.000) were inhaler technique
      at Visit 1 (OR 7.1), device type (metered dose inhaler and dry powder inhalers)
      (OR 2.2) and self-reported adherent behavior in the prior 7 days (OR 1.3). This
      research is the first to unequivocally establish a predictive relationship
      between inhaler technique maintenance and actual patient adherence, reinforcing
      the notion that inhaler technique maintenance is more than just a physical skill.
      Inhaler technique maintenance has an underlying behavioral component, which
      future studies need to investigate. ASTHMA: BEHAVIORAL ELEMENT TO CORRECT LONG
      TERM INHALER TECHNIQUES: Patients who consciously make an effort to perfect
      asthma inhaler technique will maintain their skills long-term. Elizabeth Azzi at
      the University of Sydney, Australia, and co-workers further add evidence that
      there is a strong behavioral component to patients retaining correct inhaler
      technique over time. Poor inhaler technique can limit asthma control, affecting
      quality of life and increasing the chances of severe exacerbations. Azzi's team
      followed 238 patients to determine the key predictors of inhaler technique
      maintenance from factors including age, asthma knowledge and perceived future
      risks. Correct inhaler technique at initial assessment was the strongest
      predictor of long-term success, but this was strengthened further when patients
      reported good adherence to their own medication regimen. This suggests that
      maintaining correct inhaler technique is more than just a physical skill. Careful
      guidance towards this 'practice makes perfect' approach may improve patients'
      long-term technique maintenance.

PMID- 28439077
TI  - Unravelling the drastic range retraction of an emblematic songbird of North
      Africa: potential threats to Afro-Palearctic migratory birds.
AB  - Understanding how culture may influence biodiversity is fundamental to ensure
      effective conservation, especially when the practice is local but the
      implications are global. Despite that, little effort has been devoted to
      documenting cases of culturally-related biodiversity loss. Here, we investigate
      the cultural domestication of the European goldfinch (Carduelis carduelis) in
      western Maghreb (Morocco, Algeria and Tunisia) and the effects of long-term
      poaching of wild populations (1990-2016) on range distribution, socio-economic
      value, international trading and potential collateral damage on Afro-Palearctic
      migratory birds. On average, we found that the European goldfinch lost 56.7% of
      its distribution range in the region which led to the increase of its economic
      value and establishment of international trading network in western Maghreb. One
      goldfinch is currently worth nearly a third of the average monthly income in the
      region. There has been a major change in poaching method around 2010, where
      poachers started to use mist nets to capture the species. Nearly a third of the
      16 bird species captured as by-catch of the European goldfinch poaching are
      migratory, of which one became regularly sold as cage-bird. These results suggest
      that Afro-Palearctic migratory birds could be under serious by-catch threat.

PMID- 28439078
TI  - Possible association between SIRT1 single nucleotide polymorphisms and
      predisposition to antisocial personality traits in Chinese adolescents.
AB  - Accumulating evidence suggests an association between the SIRT1 gene and human
      psychiatric disorders. The aim of the study was to investigate the association
      between SIRT1 and predisposition to antisocial personality traits (ASP) in
      Chinese adolescents. Participants consisted of 327 controls and 261 juvenile
      offenders who were diagnosed with predisposition to ASP according to the
      Personality Diagnostic Questionnaire. Four tag single nucleotide polymorphisms
      (tagSNPs) of SIRT1, namely rs12778366, rs7896005, rs10823112, and rs4746720, were
      genotyped. Association analysis between individual SNPs and ASP risk revealed the
      CC genotype of rs4746720 to be significantly associated with reduced risk of ASP
      (OR = 0.51, 95% CI = 0.33-0.77, adjusted P = 0.007). Haplotype analysis showed
      the TAAC haplotype was associated with reduced susceptibility to ASP (OR = 0.72,
      95% CI = 0.57-0.91, P = 0.005). Moreover, rs4746720 variants were found to not
      only have a direct impact on ASP susceptibility but also modulate the effect of
      alcohol consumption (Y = 0.022X + 0.431 vs. Y = -0.066X + 0.387). The present
      study is the first to report a significant association between SIRT1
      polymorphisms and ASP in adolescents. This finding is expected to aid in the
      development of effective interventions for this socially and personally costly
      disorder.

PMID- 28439079
TI  - Translation, but not transfection limits clinically relevant, exogenous mRNA
      based induction of alpha-4 integrin expression on human mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) represent promising resource of cells for
      regenerative medicine in neurological disorders. However, efficient and minimally
      invasive methods of MSCs delivery to the brain still have to be developed. Intra
      arterial route is very promising, but MSCs are missing machinery for diapedesis
      through blood-brain barrier. Thus, here we have tested a mRNA-based method to
      induce transient expression of ITGA4, an adhesion molecule actively involved in
      cell extravasation. We observed that transfection with an ITGA4-mRNA construct
      bearing a conventional cap analogue (7-methylguanosine) failed to produce ITGA4
      protein, but exogenous ITGA4-mRNA was detected in transfected MSCs. This
      indicates that not transfection, but rather translation being the major
      roadblock. Stabilization of ITGA4-mRNA with SSB proteins resulted in ITGA4
      protein synthesis in HEK293 cells only, whereas in MSCs, satisfactory results
      were obtained only after using an anti-reverse-cap-analogue (ARCA). The presence
      of ITGA4 protein in MSCs was transient and lasted for up to 24 h after
      transfection. Membranous location was confirmed by flow cytometry of viable non
      permeabilized cells using anti-ITGA4 antibody. The mRNA-based expression of itga4
      transgene is potentially sufficient for diapedesis after intra-arterial delivery.
      To conclude, mRNA-based engineering of stem cells is a rapid and integration-free
      method and attractive from the perspective of potential future clinical
      application.

PMID- 28439080
TI  - ETS Related Gene mediated Androgen Receptor Aggregation and Endoplasmic Reticulum
      Stress in Prostate Cancer Development.
AB  - Mechanistic studies of deregulated ERG in prostate cancer and other cancers
      continue to enhance its role in cancer biology and its utility as a biomarker and
      therapeutic target. Here, we show that ERG, through its physical interaction with
      androgen receptor, induces AR aggregation and endoplasmic reticulum stress in the
      prostate glands of ERG transgenic mice. Histomorphological alterations and the
      expression of ER stress sensors Atf6, Ire1alpha, Perk, their downstream effectors
      Grp78/BiP and eIF2alpha in ERG transgenic mouse prostate glands indicate the
      presence of chronic ER stress. Transient activation of apoptotic cell death
      during early age correlated well with the differential regulation of ER stress
      sensors, in particular Perk. Epithelial cells derived from ERG transgenic mouse
      prostates have increased prostasphere formation with resistance to radiation
      induced cell death. Continued activation of cell survival factors, Atf6 and
      Ire1alpha during chronic ER stress due to presence of ERG in prostate epithelium
      induces survival pathways and provides a selection pressure in the continuum of
      ERG dependent neoplastic process. These novel insights will enhance the
      understanding of the mechanistic functions of ERG in prostate tumor biology and
      towards development of early targeted therapeutic strategies for prostate cancer.

PMID- 28439081
TI  - Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a
      potential therapy for complement-mediated diseases.
AB  - Dysregulation of the complement system is linked to the pathogenesis of a variety
      of hematological disorders. Eculizumab, an anti-complement C5 monoclonal
      antibody, is the current standard of care for paroxysmal nocturnal hemoglobinuria
      (PNH) and atypical hemolytic uremic syndrome (aHUS). However, because of high
      levels of C5 in plasma, eculizumab has to be administered biweekly by intravenous
      infusion. By applying recycling technology through pH-dependent binding to C5, we
      generated a novel humanized antibody against C5, SKY59, which has long-lasting
      neutralization of C5. In cynomolgus monkeys, SKY59 suppressed C5 function and
      complement activity for a significantly longer duration compared to a
      conventional antibody. Furthermore, epitope mapping by X-ray crystal structure
      analysis showed that a histidine cluster located on C5 is crucial for the pH
      dependent interaction with SKY59. This indicates that the recycling effect of
      SKY59 is driven by a novel mechanism of interaction with its antigen and is
      distinct from other known pH-dependent antibodies. Finally, SKY59 showed
      neutralizing effect on C5 variant p.Arg885His, while eculizumab does not inhibit
      complement activity in patients carrying this mutation. Collectively, these
      results suggest that SKY59 is a promising new anti-C5 agent for patients with PNH
      and other complement-mediated disorders.

PMID- 28439083
TI  - A novel way to establish fertilization recommendations based on agronomic
      efficiency and a sustainable yield index for rice crops.
AB  - A simpler approach for establishing fertilizer recommendations for major crops is
      urgently required to improve the application efficiency of commercial fertilizers
      in China. To address this need, we developed a method based on field data drawn
      from the China Program of the International Plant Nutrition Institute (IPNI) rice
      experiments and investigations carried out in southeastern China during 2001 to
      2012. Our results show that, using agronomic efficiencies and a sustainable yield
      index (SYI), this new method for establishing fertilizer recommendations robustly
      estimated the mean rice yield (7.6 t/ha) and mean nutrient supply capacities
      (186, 60, and 96 kg/ha of N, P2O5, and K2O, respectively) of fertilizers in the
      study region. In addition, there were significant differences in rice yield
      response, economic cost/benefit ratio, and nutrient-use efficiencies associated
      with agronomic efficiencies ranked as high, medium and low. Thus, ranking
      agronomic efficiency could strengthen linear models relating rice yields and SYI.
      Our results also indicate that the new method provides better recommendations in
      terms of rice yield, SYI, and profitability than previous methods. Hence, we
      believe it is an effective approach for improving recommended applications of
      commercial fertilizers to rice (and potentially other crops).

PMID- 28439082
TI  - Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and
      aggressive breast cancer.
AB  - We here examined whether Nestin, by protein and mRNA levels, could be a predictor
      of BRCA1 related breast cancer, a basal-like phenotype, and aggressive tumours.
      Immunohistochemical staining of Nestin was done in independent breast cancer
      hospital cohorts (Series I-V, total 1257 cases). Also, TCGA proteomic data (n =
      103), mRNA microarray data from TCGA (n = 520), METABRIC (n = 1992), and 6 open
      access breast cancer datasets (n = 1908) were analysed. Patients with Nestin
      protein expression in tumour cells more often had BRCA1 germline mutations (OR
      8.7, p < 0.0005, Series III), especially among younger patients (<40 years at
      diagnosis) (OR 16.5, p = 0.003). Nestin protein positivity, observed in 9-28% of
      our hospital cases (Series I-IV), was independently associated with reduced
      breast cancer specific survival (HR = 2.0, p = 0.035) and was consistently
      related to basal-like differentiation (by Cytokeratin 5, OR 8.7-13.8, p < 0.0005;
      P-cadherin OR 7.0-8.9, p < 0.0005; EGFR staining, OR 3.7-8.2, p <= 0.05). Nestin
      mRNA correlated significantly with Nestin protein expression (rho = 0.6, p <
      0.0005), and high levels were seen in the basal-like intrinsic subtype. Gene
      expression signalling pathways linked to high Nestin were explored, and revealed
      associations with stem-like tumour features. In summary, Nestin was strongly
      associated with germline BRCA1 related breast cancer, a basal-like phenotype,
      reduced survival, and stemness characteristics.

PMID- 28439084
TI  - Preparation of heterostructured WO3/TiO2 catalysts from wood fibers and its
      versatile photodegradation abilities.
AB  - A facile route was adopted to synthesize heterostructured WO3/TiO2 photocatalysts
      from wood fibers through a two-steps hydrothermal method and a calcination
      process. The prepared WO3/TiO2-wood fibers were used as photocatalysts under UV
      irradiation for photodegradation of rhodamine B, methylene blue and methyl
      orange. In calcination process, the wood fibers acted as carbon substrates to
      prepare the WO3/TiO2 photocatalysts with high surface area and unique morphology.
      Thus, the significant enhanced photodegradation efficiency of the organic
      pollutants with the WO3/TiO2-wood fibers under UV irradiation was obtained. The
      photodegradation rates are measured which confirms the highest performance of the
      WO3/TiO2-wood fibers after calcination in comparison to the TiO2-wood fibers
      after calcination and the pure WO3/TiO2 after calcination. Moreover, the
      photodegradation efficiency of the WO3/TiO2-wood fibers after calcination under
      visible light is high. Our results demonstrated that the WO3/TiO2-wood fibers
      after calcination are a promising candidate for wastewater treatment in practical
      application.

PMID- 28439085
TI  - A high-power and fast charging Li-ion battery with outstanding cycle-life.
AB  - Electrochemical energy storage devices based on Li-ion cells currently power
      almost all electronic devices and power tools. The development of new Li-ion cell
      configurations by incorporating innovative functional components (electrode
      materials and electrolyte formulations) will allow to bring this technology
      beyond mobile electronics and to boost performance largely beyond the state-of
      the-art. Here we demonstrate a new full Li-ion cell constituted by a high
      potential cathode material, i.e. LiNi0.5Mn1.5O4, a safe nanostructured anode
      material, i.e. TiO2, and a composite electrolyte made by a mixture of an ionic
      liquid suitable for high potential applications, i.e. Pyr1,4PF6, a lithium salt,
      i.e. LiPF6, and standard organic carbonates. The final cell configuration is able
      to reversibly cycle lithium for thousands of cycles at 1000 mAg-1 and a capacity
      retention of 65% at cycle 2000.

PMID- 28439088
TI  - Effects of molecular weight on the optical and electrochemical properties of EDOT
      based pi-conjugated polymers.
AB  - Absolute molecular weight values obtained by gel permeation chromatography with
      multi angle light scattering of PEDOTF8 were approximately 65% of the relative
      molecular weight values obtained by gel permeation chromatography using
      polystyrene standards. Both light absorption and molecular weight measurements
      showed the effective conjugation lengths (absolute molecular weight <2600,
      relative molecular weight <4000, number of EDOT-F8 units: n < ca. 5 unit). The
      low molecular weight polymers showed higher energy absorption and fluorescence
      bands. Molecular weight also affected the electrochemical process of the polymer
      films. The high molecular weight PEDOTF8 (number average molecular weight >70000)
      showed a higher redox stability than the low molecular weight one. The two
      polymers with number average molecular weights of 70200 and 40000 retained 65%
      and 25% of the charge storage capacity after 100 electrochemical scans,
      respectively. Square-wave potential step absorptiometry measurements of the
      polymers with number average molecular weights of 70200 and 40000 showed that the
      optical contrasts remain stable after ca. 55 and three cycles, respectively. The
      high molecular weight polymer has a high electrochemical stability and would be a
      good material for optoelectronic devices.

PMID- 28439086
TI  - Quality and freshness of human bone marrow-derived mesenchymal stem cells
      decrease over time after trypsinization and storage in phosphate-buffered saline.
AB  - Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have been studied for
      their therapeutic potential. However, evaluating the quality of hBM-MSCs before
      transplantation remains a challenge. We addressed this issue in the present study
      by investigating deformation, the expression of genes related to reactive oxygen
      species (ROS) generation, changes in amino acid profiles, and membrane fluidity
      in hBM-MSCs. Deformability and cell size were decreased after storage for 6 and
      12 h, respectively, in phosphate-buffered saline. Intracellular ROS levels also
      increased over time, which was associated with altered expression of genes
      related to ROS generation and amino acid metabolism. Membrane fluidity
      measurements revealed higher Laurdan generalized polarization values at 6 and 12
      h; however, this effect was reversed by N-acetyl-L-cysteine-treatment. These
      findings indicate that the quality and freshness of hBM-MSCs is lost over time
      after dissociation from the culture dish for transplantation, highlighting the
      importance of using freshly trypsinized cells in clinical applications.

PMID- 28439087
TI  - 3D Microfluidic model for evaluating immunotherapy efficacy by tracking dendritic
      cell behaviour toward tumor cells.
AB  - Immunotherapy efficacy relies on the crosstalk within the tumor microenvironment
      between cancer and dendritic cells (DCs) resulting in the induction of a potent
      and effective antitumor response. DCs have the specific role of recognizing
      cancer cells, taking up tumor antigens (Ags) and then migrating to lymph nodes
      for Ag (cross)-presentation to naive T cells. Interferon-alpha-conditioned DCs
      (IFN-DCs) exhibit marked phagocytic activity and the special ability of inducing
      Ag-specific T-cell response. Here, we have developed a novel microfluidic
      platform recreating tightly interconnected cancer and immune systems with
      specific 3D environmental properties, for tracking human DC behaviour toward
      tumor cells. By combining our microfluidic platform with advanced microscopy and
      a revised cell tracking analysis algorithm, it was possible to evaluate the
      guided efficient motion of IFN-DCs toward drug-treated cancer cells and the
      succeeding phagocytosis events. Overall, this platform allowed the dissection of
      IFN-DC-cancer cell interactions within 3D tumor spaces, with the discovery of
      major underlying factors such as CXCR4 involvement and underscored its potential
      as an innovative tool to assess the efficacy of immunotherapeutic approaches.

PMID- 28439089
TI  - Transcriptome analysis on the exoskeleton formation in early developmetal stages
      and reconstruction scenario in growth-moulting in Litopenaeus vannamei.
AB  - Exoskeleton construction is an important issue in shrimp. To better understand
      the molecular mechanism of exoskeleton formation, development and reconstruction,
      the transcriptome of the entire developmental process in Litopenaeus vannamei,
      including nine early developmental stages and eight adult-moulting stages, was
      sequenced and analysed using Illumina RNA-seq technology. A total of 117,539
      unigenes were obtained, with 41.2% unigenes predicting the full-length coding
      sequence. Gene Ontology, Clusters of Orthologous Group (COG), the Kyoto
      Encyclopedia of Genes and Genomes (KEGG) analysis and functional annotation of
      all unigenes gave a better understanding of the exoskeleton developmental process
      in L. vannamei. As a result, more than six hundred unigenes related to
      exoskeleton development were identified both in the early developmental stages
      and adult-moulting. A cascade of sequential expression events of exoskeleton
      related genes were summarized, including exoskeleton formation, regulation,
      synthesis, degradation, mineral absorption/reabsorption, calcification and
      hardening. This new insight on major transcriptional events provide a deep
      understanding for exoskeleton formation and reconstruction in L. vannamei. In
      conclusion, this is the first study that characterized the integrated
      transcriptomic profiles cover the entire exoskeleton development from zygote to
      adult-moulting in a crustacean, and these findings will serve as significant
      references for exoskeleton developmental biology and aquaculture research.

PMID- 28439090
TI  - SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell
      mediated reactions in vivo.
AB  - Mast cells act as sensors in innate immunity and as effector cells in adaptive
      immune reactions. Here we demonstrate that SLC10A4, also referred to as the
      vesicular aminergic-associated transporter, VAAT, modifies mast cell
      degranulation. Strikingly, Slc10a4 -/- bone marrow-derived mast cells (BMMCs) had
      a significant reduction in the release of granule-associated mediators in
      response to IgE/antigen-mediated activation, whereas the in vitro development of
      mast cells, the storage of the granule-associated enzyme mouse mast cell protease
      6 (mMCP-6), and the release of prostaglandin D2 and IL-6 were normal. Slc10a4
      deficient mice had a strongly reduced passive cutaneous anaphylaxis reaction and
      a less intense itching behaviour in response to the mast cell degranulator 48/80.
      Live imaging of the IgE/antigen-mediated activation showed decreased
      degranulation and that ATP was retained to a higher degree in mast cell granules
      lacking SLC10A4. Furthermore, ATP was reduced by two thirds in Slc10a4 -/- BMMCs
      supernatants in response to IgE/antigen. We speculate that SLC10A4 affects the
      amount of granule-associated ATP upon IgE/antigen-induced mast cell activation,
      which affect the release of granule-associated mast cell mediators. In summary,
      SLC10A4 acts as a regulator of degranulation in vitro and of mast cell-related
      reactions in vivo.

PMID- 28439091
TI  - Abdominal adiposity intensifies the negative effects of ambient air pollution on
      lung function in Korean men.
AB  - BACKGROUND: Some studies have provided the possibility that adipose tissue may
      mediate air pollution-induced lung dysfunction. Studies using quantified fat mass
      data are needed to understand the biological mechanisms between adipocyte and air
      pollution in lung function. We aimed to investigate whether abdominal adiposity
      measured by computed tomography (CT) modifies the effects of air pollution on
      lung function in Korean men. METHODS: A total of 1876 men who visited one of two
      health checkup centers were recruited for this study. Adiposity traits such as
      visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total
      adipose tissue (TAT) areas were measured by CT. We used the annual mean
      concentrations of ambient air pollutants including nitrogen dioxide (NO2) and
      particulate matter with an aerodynamic diameter ?10 MUm (PM10). RESULTS:
      Interquartile range (IQR) increase in annual mean concentration of NO2 was
      significantly associated with a 2.5% lower forced expiratory volume in 1 s (FEV1)
      and 2.9% lower forced vital capacity (FVC) (both P<0.05). The decrease in lung
      function was more strongly associated with adiposity traits than with body mass
      index. In a stratified analysis of adiposity, compared with subjects with low-VAT
      area (VAT?200 cm2), those with high-VAT area (VAT>200 cm2) showed a rapid
      decrease in FEV1 with each IQR increase in PM10 (beta=-0.0812; 95% confidence
      interval (CI) =-0.1590, -0.0035) and NO2 (beta=-0.0979; 95% CI=-0.1611, -0.0346).
      In the high-VAT group, each IQR increase in NO2 content was significantly
      associated with a 10.6% decrease (beta=-0.1056; 95% CI=-0.1770, -0.0343) in FVC.
      SAT and TAT areas showed similar patterns. CONCLUSIONS: We report the first
      finding that abdominal adiposity intensifies the inverse relationship between air
      pollution and lung function.

PMID- 28439092
TI  - Timeline of changes in appetite during weight loss with a ketogenic diet.
AB  - BACKGROUND/OBJECTIVE: Diet-induced weight loss (WL) leads to increased hunger and
      reduced fullness feelings, increased ghrelin and reduced satiety peptides
      concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide
      YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses.
      The aim of this study was to determine the timeline over which changes in
      appetite occur during progressive WL with a ketogenic very-low-energy diet
      (VLED). SUBJECTS/METHODS: Thirty-one sedentary adults (18 men), with obesity
      (body mass index: 37+/-4.5 kg m-2) underwent 8 weeks (wks) of a VLED followed by
      4 wks of weight maintenance. Body weight and composition, subjective feelings of
      appetite and appetite-related hormones (insulin, active ghrelin (AG), active GLP
      1, total PYY and CCK) were measured in fasting and postprandially, at baseline,
      on day 3 of the diet, 5 and 10% WL, and at wks 9 and 13. Data are shown as mean+/
      s.d. RESULTS: A significant increase in fasting hunger was observed by day 3 (2+/
      1% WL), (P<0.01), 5% WL (12+/-8 days) (P<0.05) and wk 13 (17+/-2% WL) (P<0.05).
      Increased desire to eat was observed by day 3 (P<0.01) and 5% WL (P<0.05).
      Postprandial prospective food consumption was significantly reduced at wk 9 (16+/
      2% WL) (P<0.01). Basal total PYY was significantly reduced at 10% WL (32+/-8
      days) (P<0.05). Postprandial active GLP-1 was increased at 5% WL (P<0.01) and CCK
      reduced at 5 and 10% WL (P<0.01, for both) and wk 9 (P<0.001). Basal and
      postprandial AG were significantly increased at wk 13 (P<0.001, both).
      CONCLUSIONS: WL with a ketogenic VLED transiently increases the drive to eat up
      to 3 weeks (5% WL). After that, and while participants are ketotic, a 10-17% WL
      is not associated with increased appetite. However, hunger feelings and AG
      concentrations increase significantly from baseline, once refeeding occurs.

PMID- 28439093
TI  - Gene expression profile of subcutaneous adipose tissue in BMI-discordant
      monozygotic twin pairs unravels molecular and clinical changes associated with
      sub-types of obesity.
AB  - BACKGROUND: Subcutaneous adipose tissue (SAT) undergoes major changes in obesity,
      but little is known about the whole-genome scale patterns of these changes or
      about their variation between different obesity sub-groups. We sought to compare
      how transcriptomics profiles in SAT differ between monozygotic (MZ) co-twins who
      are discordant for body mass index (BMI), whether the profiles vary between twin
      pairs and whether the variation can be linked to clinical characteristics.
      METHODS: We analysed the transcriptomics (Affymetrix U133 Plus 2.0) patterns of
      SAT in young MZ twin pairs (n=26, intra-pair difference in BMI >3 kg m-2, aged 23
      36), from 10 birth cohorts of adult Finnish twins. The clinical data included
      measurements of body composition, insulin resistance, lipids and adipokines.
      RESULTS: We found 2108 genes differentially expressed (false discovery rate
      (FDR)<0.05) in SAT of the BMI-discordant pairs. Pathway analyses of these genes
      revealed a significant downregulation of mitochondrial oxidative pathways
      (P<0.05) and upregulation of inflammation pathways (P<0.05). Hierarchical
      clustering of heavy/lean twin ratios, representing effects of acquired obesity in
      the transcriptomics data, revealed three sub-groups with different molecular
      profiles (FDR<0.05). Analyses comparing these sub-groups showed that, in the
      heavy co-twins, downregulation of the mitochondrial pathways, especially that of
      branched chain amino acid degradation was more evident in two clusters while and
      upregulation of the inflammatory response was most evident in the last,
      presumably the unhealthiest cluster. High-fasting insulin levels and large
      adipocyte diameter were the predominant clinical characteristic of the heavy co
      twins in this cluster (Bonferroni-adjusted P<0.05). CONCLUSIONS: This is the
      first study in BMI-discordant MZ twin pairs reporting sub-types of obesity based
      on both SAT gene expression profiles and clinical traits. We conclude that a
      decrease in mitochondrial BCAA degradation and an increase in inflammation in SAT
      co-occur and associate with hyperinsulinemia and large adipocyte size in
      unhealthy obesity.

PMID- 28439095
TI  - Corrigendum: Novel KCNB1 mutation associated with non-syndromic intellectual
      disability.

PMID- 28439096
TI  - A message for 2017.

PMID- 28439094
TI  - Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel
      Curcumin Analogs.
AB  - Recently, research has focused on targeting the oxidative and metabolic
      vulnerabilities in cancer cells. Natural compounds like curcumin that target such
      susceptibilities have failed further clinical advancements due to the poor
      stability and bioavailability as well as the need of high effective doses. We
      have synthesized and evaluated the anti-cancer activity of several monocarbonyl
      analogs of curcumin. Interestingly, two novel analogs (Compound A and I) in
      comparison to curcumin, have increased chemical stability and have greater anti
      cancer activity in a variety of human cancer cells, including triple-negative,
      inflammatory breast cancer cells. In particular, the generation of reactive
      oxygen species was selective to cancer cells and occurred upstream of
      mitochondrial collapse and execution of apoptosis. Furthermore, Compound A in
      combination with another cancer-selective/pro-oxidant, piperlongumine, caused an
      enhanced anti-cancer effect. Most importantly, Compound A was well tolerated by
      mice and was effective in inhibiting the growth of human triple-negative breast
      cancer and leukemia xenografts in vivo when administered intraperitoneally. Thus,
      exploiting oxidative vulnerabilities in cancer cells could be a selective and
      efficacious means to eradicate malignant cells as demonstrated by the curcumin
      analogs presented in this report with high therapeutic potential.

PMID- 28439097
TI  - The 2016 JHG Young Scientist Award.

PMID- 28439098
TI  - Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant
      like effects.
AB  - Several preclinical studies have reported the rapid antidepressant effects of N
      methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying
      mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples
      GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In
      the present study, we found that chronic unpredictable stress (CUS) induced
      extracellular glutamate accumulation, accompanied by an increase in the DAPK1
      NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at
      Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein
      deficits in the rat medial prefrontal cortex (mPFC). CUS also enhanced GluN2B
      mediated NMDA currents and extrasynaptic responses that were induced by bursts of
      high-frequency stimulation, which may be associated with the loss of astrocytes
      and low expression of glutamate transporter-1 (GLT-1). The blockade of GLT-1 in
      the mPFC was sufficient to induce depressive-like behavior and cause similar
      molecular changes. Selective GluN2B antagonist, DAPK1 knockdown by adeno
      associated virus-mediated short-hairpin RNA or a pharmacological inhibitor, and
      the uncoupling of DAPK1 from the NMDAR GluN2B subunit produced rapid
      antidepressant-like effects and reversed CUS-induced alterations in the mPFC. The
      inhibition of DAPK1 and its interaction with GluN2B subunit in the mPFC also
      rescued CUS-induced depressive-like behavior 7 days after treatment. A selective
      GluN2B antagonist did not have rewarding effects in the conditioned place
      preference paradigm. Altogether, our findings suggest that the DAPK1 interaction
      with the NMDAR GluN2B subunit acts as a critical component in the pathophysiology
      of depression and is a potential target for new antidepressant treatments.

PMID- 28439099
TI  - Optogenetic silencing of a corticotropin-releasing factor pathway from the
      central amygdala to the bed nucleus of the stria terminalis disrupts sustained
      fear.
AB  - The lateral central nucleus of the amygdala (CeAL) and the dorsolateral bed
      nucleus of the stria terminalis (BNSTDL) coordinate the expression of shorter-
      and longer-lasting fears, respectively. Less is known about how these structures
      communicate with each other during fear acquisition. One pathway, from the CeAL
      to the BNSTDL, is thought to communicate via corticotropin-releasing factor
      (CRF), but studies have yet to examine its function in fear learning and memory.
      Thus, we developed an adeno-associated viral-based strategy to selectively target
      CRF neurons with the optogenetic silencer archaerhodopsin tp009 (CRF-ArchT) to
      examine the role of CeAL CRF neurons and projections to the BNSTDL during the
      acquisition of contextual fear. Expression of our CRF-ArchT vector injected into
      the amygdala was restricted to CeAL CRF neurons. Furthermore, CRF axonal
      projections from the CeAL clustered around BNSTDL CRF cells. Optogenetic
      silencing of CeAL CRF neurons during contextual fear acquisition disrupted
      retention test freezing 24 h later, but only at later time points (>6 min) during
      testing. Silencing CeAL CRF projections in the BNSTDL during contextual fear
      acquisition produced a similar effect. Baseline contextual freezing, the rate of
      fear acquisition, freezing in an alternate context after conditioning and
      responsivity to foot shock were unaffected by optogenetic silencing. Our results
      highlight how CeAL CRF neurons and projections to the BNSTDL consolidate longer
      lasting components of a fear memory. Our findings have implications for
      understanding how discrete amygdalar CRF pathways modulate longer-lasting fear in
      anxiety- and trauma-related disorders.

PMID- 28439100
TI  - Ventral striatal regulation of CREM mediates impulsive action and drug addiction
      vulnerability.
AB  - Impulsivity, a multifaceted behavioral hallmark of attention
      deficit/hyperactivity disorder (ADHD), strongly influences addiction
      vulnerability and other psychiatric disorders that incur enormous medical and
      societal burdens yet the neurobiological underpinnings linking impulsivity to
      disease remain poorly understood. Here we report the critical role of ventral
      striatal cAMP-response element modulator (CREM) in mediating impulsivity relevant
      to drug abuse vulnerability. Using an ADHD rat model, we demonstrate that
      impulsive animals are neurochemically and behaviorally more sensitive to heroin
      and exhibit reduced Crem expression in the nucleus accumbens core. Virally
      increasing Crem levels decreased impulsive action, thus establishing a causal
      relationship. Genetic studies in seven independent human populations illustrate
      that a CREM promoter variant at rs12765063 is associated with impulsivity,
      hyperactivity and addiction-related phenotypes. We also reveal a role of Crem in
      regulating striatal structural plasticity. Together, these results highlight that
      ventral striatal CREM mediates impulsivity related to substance abuse and suggest
      that CREM and its regulated network may be promising therapeutic targets.

PMID- 28439102
TI  - MeCP2-regulated miRNAs control early human neurogenesis through differential
      effects on ERK and AKT signaling.
AB  - Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily
      by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a
      multifunctional epigenetic regulator with known links to a wide spectrum of
      neuropsychiatric disorders. Although postnatal functions of MeCP2 have been
      thoroughly investigated, its role in prenatal brain development remains poorly
      understood. Given the well-established importance of microRNAs (miRNAs) in
      neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent
      stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify
      novel MeCP2-regulated miRNAs enriched during early human neuronal development.
      Focusing on the most dysregulated miRNAs, we found miR-199 and miR-214 to be
      increased during early brain development and to differentially regulate
      extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase and
      protein kinase B (PKB/AKT) signaling. In parallel, we characterized the effects
      on human neurogenesis and neuronal differentiation brought about by MeCP2
      deficiency using both monolayer and three-dimensional (cerebral organoid) patient
      derived and MeCP2-deficient neuronal culture models. Inhibiting miR-199 or miR
      214 expression in iPSC-derived neural progenitors deficient in MeCP2 restored AKT
      and ERK activation, respectively, and ameliorated the observed alterations in
      neuronal differentiation. Moreover, overexpression of miR-199 or miR-214 in the
      wild-type mouse embryonic brains was sufficient to disturb neurogenesis and
      neuronal migration in a similar manner to Mecp2 knockdown. Taken together, our
      data support a novel miRNA-mediated pathway downstream of MeCP2 that influences
      neurogenesis via interactions with central molecular hubs linked to autism
      spectrum disorders.

PMID- 28439101
TI  - Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex
      differences in heritability.
AB  - The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC
      PTSD) combined genome-wide case-control molecular genetic data across 11
      multiethnic studies to quantify PTSD heritability, to examine potential shared
      genetic risk with schizophrenia, bipolar disorder, and major depressive disorder
      and to identify risk loci for PTSD. Examining 20 730 individuals, we report a
      molecular genetics-based heritability estimate (h2SNP) for European-American
      females of 29% that is similar to h2SNP for schizophrenia and is substantially
      higher than h2SNP in European-American males (estimate not distinguishable from
      zero). We found strong evidence of overlapping genetic risk between PTSD and
      schizophrenia along with more modest evidence of overlap with bipolar and major
      depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome
      wide significance in the transethnic (overall) meta-analysis and we do not
      replicate previously reported associations. Still, SNP-level summary statistics
      made available here afford the best-available molecular genetic index of PTSD-for
      both European- and African-American individuals-and can be used in polygenic risk
      prediction and genetic correlation studies of diverse phenotypes. Publication of
      summary statistics for ~10 000 African Americans contributes to the broader goal
      of increased ancestral diversity in genomic data resources. In sum, the results
      demonstrate genetic influences on the development of PTSD, identify shared
      genetic risk between PTSD and other psychiatric disorders and highlight the
      importance of multiethnic/racial samples. As has been the case with schizophrenia
      and other complex genetic disorders, larger sample sizes are needed to identify
      specific risk loci.

PMID- 28439103
TI  - Brain age predicts mortality.
AB  - Age-associated disease and disability are placing a growing burden on society.
      However, ageing does not affect people uniformly. Hence, markers of the
      underlying biological ageing process are needed to help identify people at
      increased risk of age-associated physical and cognitive impairments and
      ultimately, death. Here, we present such a biomarker, 'brain-predicted age',
      derived using structural neuroimaging. Brain-predicted age was calculated using
      machine-learning analysis, trained on neuroimaging data from a large healthy
      reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669),
      to determine relationships with age-associated functional measures and mortality.
      Having a brain-predicted age indicative of an older-appearing brain was
      associated with: weaker grip strength, poorer lung function, slower walking
      speed, lower fluid intelligence, higher allostatic load and increased mortality
      risk. Furthermore, while combining brain-predicted age with grey matter and
      cerebrospinal fluid volumes (themselves strong predictors) not did improve
      mortality risk prediction, the combination of brain-predicted age and DNA
      methylation-predicted age did. This indicates that neuroimaging and epigenetics
      measures of ageing can provide complementary data regarding health outcomes. Our
      study introduces a clinically-relevant neuroimaging ageing biomarker and
      demonstrates that combining distinct measurements of biological ageing further
      helps to determine risk of age-related deterioration and death.

PMID- 28439105
TI  - Autism spectrum disorders: a meta-analysis of executive function.
AB  - Evidence of executive dysfunction in autism spectrum disorders (ASD) across
      development remains mixed and establishing its role is critical for guiding
      diagnosis and intervention. The primary objectives of this meta-analysis is to
      analyse executive function (EF) performance in ASD, the fractionation across EF
      subdomains, the clinical utility of EF measures and the influence of multiple
      moderators (for example, age, gender, diagnosis, measure characteristics). The
      Embase, Medline and PsychINFO databases were searched to identify peer-reviewed
      studies published since the inclusion of Autism in DSM-III (1980) up to end of
      June 2016 that compared EF in ASD with neurotypical controls. A random-effects
      model was used and moderators were tested using subgroup analysis. The primary
      outcome measure was Hedges' g effect size for EF and moderator factors. Clinical
      sensitivity was determined by the overlap percentage statistic (OL%). Results
      were reported according to the PRISMA (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses) guidelines. A total of 235 studies comprising 14 081
      participants were included (N, ASD=6816, Control=7265). A moderate overall effect
      size for reduced EF (Hedges' g=0.48, 95% confidence interval (CI) 0.43-0.53) was
      found with similar effect sizes across each domain. The majority of moderator
      comparisons were not significant although the overall effect of executive
      dysfunction has gradually reduced since the introduction of ASD. Only a small
      number of EF measures achieved clinical sensitivity. This study confirms a broad
      executive dysfunction in ASD that is relatively stable across development. The
      fractionation of executive dysfunction into individual subdomains was not
      supported, nor was diagnostic sensitivity. Development of feasible EF measures
      focussing on clinical sensitivity for diagnosis and treatment studies should be a
      priority.

PMID- 28439104
TI  - A novel 5HT3 receptor-IGF1 mechanism distinct from SSRI-induced antidepressant
      effects.
AB  - Depression is a common mental disorder affecting around 350 million people
      worldwide. Although selective serotonin reuptake inhibitors (SSRIs) are the most
      widely used antidepressants, a significant proportion of depressed patients do
      not achieve remission with SSRIs. In this study, we show that a serotonin type 3
      receptor (5HT3R) agonist induces antidepressant effects as well as hippocampal
      neurogenesis independent of fluoxetine (a commonly used SSRI). Notably, our
      histological analysis reveals that 5HT3R and insulin-like growth factor 1 (IGF1)
      are expressed in the same neurons in the subgranular zone of the hippocampal
      dentate gyrus. Furthermore, our in vivo microdialysis analysis shows that 5HT3R
      regulates hippocampal extracellular IGF1 levels, and we also show that 5HT3R
      dependent hippocampal neurogenesis is mediated by increased IGF1 levels.
      Altogether, our findings suggest a novel 5HT3R-IGF1 mechanism that is distinct
      from fluoxetine-induced responses and that provides a new therapeutic target for
      depression, especially bringing significant benefits for SSRI-resistant depressed
      patients.

PMID- 28439106
TI  - Lenalidomide, adriamycin, dexamethasone for induction followed by stem-cell
      transplant in newly diagnosed myeloma.

PMID- 28439107
TI  - E-selectin ligands recognised by HECA452 induce drug resistance in myeloma, which
      is overcome by the E-selectin antagonist, GMI-1271.
AB  - Multiple myeloma (MM) is characterized by the clonal expansion and metastatic
      spread of malignant plasma cells to multiple sites in the bone marrow (BM).
      Recently, we implicated the sialyltransferase ST3Gal-6, an enzyme critical to the
      generation of E-selectin ligands, in MM BM homing and resistance to therapy.
      Since E-selectin is constitutively expressed in the BM microvasculature, we
      wished to establish the contribution of E-selectin ligands to MM biology. We
      report that functional E-selectin ligands are restricted to a minor subpopulation
      of MM cell lines which, upon expansion, demonstrate specific and robust
      interaction with recombinant E-selectin in vitro. Moreover, an increase in the
      mRNA levels of genes involved in the generation of E-selectin ligands was
      associated with inferior progression-free survival in the CoMMpass study. In
      vivo, E-selectin ligand-enriched cells induced a more aggressive disease and were
      completely insensitive to Bortezomib. Importantly, this resistance could be
      reverted by co-administration of GMI-1271, a specific glycomimetic antagonist of
      E-selectin. Finally, we report that E-selectin ligand-bearing cells are present
      in primary MM samples from BM and peripheral blood with a higher proportion seen
      in relapsed patients. This study provides a rationale for targeting E-selectin
      receptor/ligand interactions to overcome MM metastasis and chemoresistance.

PMID- 28439108
TI  - Phase I trial of systemic administration of Edmonston strain of measles virus
      genetically engineered to express the sodium iodide symporter in patients with
      recurrent or refractory multiple myeloma.
AB  - MV-NIS is an Edmonston lineage oncolytic measles virus expressing the human
      sodium iodide symporter-a means for monitoring by non-invasive imaging of
      radioiodine. Patients with relapsed, refractory myeloma who had explored all
      other treatment options were eligible for this Phase I trial. Cohort 1 was
      treated with intravenous MV-NIS, and Cohort 2 received cyclophosphamide 2 days
      prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to
      four dose levels without reaching maximum tolerated dose (MTD) and subsequently
      to two higher dose levels when improved virus manufacture technology made it
      possible. MTD was not reached in Cohort 1, and TCID50 1011 is the dose being used
      in a Phase II trial of single agent MV-NIS. Grade 3-4 adverse events in both
      cohorts at all dose levels were: neutropenia (n=9); leukocyte count decreased
      (n=5); thrombocytopenia (n=2); and CD4 lymphocytes decreased, anemia and
      lymphopenia (each n=1). MV-N RNA sequences were amplified from gargle specimens,
      blood and urine. 123I scans were positive in eight patients. One patient achieved
      a complete response; transient drops in serum free light chains were seen in
      other patients. MV-NIS is capable of replicating before being cleared by the
      immune system. Oncolytic viruses offer a promising new modality for the targeted
      infection and destruction of disseminated myeloma.

PMID- 28439109
TI  - Efficacy and safety of carfilzomib regimens in multiple myeloma patients
      relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes.
AB  - Autologous stem cell transplantation (ASCT) is a standard treatment for eligible
      multiple myeloma (MM) patients, but many patients will relapse after ASCT and
      require subsequent therapy. The proteasome inhibitor carfilzomib is approved for
      relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens
      (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib
      dexamethasone) demonstrated superior progression-free survival (PFS) compared
      with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR,
      bortezomib-dexamethasone). This subgroup analysis of ASPIRE and ENDEAVOR
      evaluated outcomes according to prior ASCT status. In total, 446 patients in
      ASPIRE and 538 in ENDEAVOR had prior ASCT. Median PFS was longer for carfilzomib
      based regimens vs non-carfilzomib-based regimens for patients with prior ASCT
      (ASPIRE: 26.3 vs 17.8 months (hazard ratio (HR)=0.68); ENDEAVOR: not estimable vs
      10.2 months (HR=0.61)), those with one prior line of therapy that included ASCT
      (ASPIRE: 29.7 vs 17.8 months (HR=0.70); ENDEAVOR: not estimable vs 11.2 months
      (HR=0.46)), and those without prior ASCT (ASPIRE: 26.4 vs 16.6 months (HR=0.76);
      ENDEAVOR: 17.7 vs 8.5 months (HR=0.43)). Overall response rates also favored the
      carfilzomib-based regimens. No new safety signals were detected. This analysis
      suggests that carfilzomib-based treatment may lead to improvement in PFS and
      response rates regardless of prior transplant status. Further evaluation is
      warranted.

PMID- 28439110
TI  - Characterization of the leukemogenic potential of distal cytoplasmic CSF3R
      truncation and missense mutations.
AB  - An increasing number of variants of unknown significance are being identified in
      leukemia patients with the application of deep sequencing and these include CSF3R
      cytoplasmic mutations. Previous studies have demonstrated oncogenic potential of
      certain CSF3R truncation mutations prior to internalization motifs. However, the
      oncogenic potential of truncating the more distal region of CSF3R cytoplasmic
      domain as well as cytoplasmic missense mutations remains uncharacterized. Here we
      identified that CSF3R distal cytoplasmic truncation mutations (Q793-Q823) also
      harbored leukemogenic potential. Mechanistically, these distal cytoplasmic
      truncation mutations demonstrated markedly decreased receptor degradation,
      probably owing to loss of the de-phosphorylation domain (residues N818-F836).
      Furthermore, all truncations prior to Q823 demonstrated increased expression of
      the higher molecular weight CSF3R band, which is shown to be essential for the
      receptor surface expression and the oncogenic potential. We further demonstrated
      that sufficient STAT5 activation is essential for oncogenic potential. In
      addition, CSF3R K704A demonstrated transforming capacity due to interruption of
      receptor ubiquitination and degradation. In summary, we have expanded the region
      of the CSF3R cytoplasmic domain in which truncation or missense mutations exhibit
      leukemogenic capacity, which will be useful for evaluating the relevance of CSF3R
      mutations in patients and helpful in defining targeted therapy strategies.

PMID- 28439111
TI  - Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: updated
      ERIC recommendations.

PMID- 28439112
TI  - Tubular atrophy/interstitial fibrosis scores of Oxford classification combinded
      with proteinuria level at biopsy provides earlier risk prediction in lgA
      nephropathy.
AB  - The predictive effect of combining MEST with clinical data at biopsy on renal
      survival outcomes has not been investigated in patients with IgA nephropathy
      (IgAN). MEST of The Oxford classification of IgAN and 24-hour urine proteinuia
      measured at enrollment. The primary outcome was a composite of either ESRD (eGFR
      to <15 ml/min per 1.73 m2), or a permanent reduction in eGFR to below 50% of the
      value at biopsy. 742 patients were enrolled and follow-up >3 years, and were
      divided into two groups according to eGFR levels at biopsy. Multivariable
      logistical regression revealed that proteinuria at biopsy (OR 5.307 (95% Cl 3.003
      to 9.376) p = 0.000), tubular atrophy/interstitial fibrosis scores (T) in MEST
      (OR 3.915 (95%Cl 2.710 to 5.654) p = 0.000) were the two predictors of eGFR
      decline for IgAN patients. Kaplan-Meier survival curves show significant
      difference in renal survival outcome among each T scores groups at biopsy (T0,
      T1, T2) (P < 0.05) and proteinuria levels at biopsy (P < 0.05), individially.
      Patients with T2 combined proteinuria at biopsy have the worst renal survival
      outcome. In conclusion, T scores in MEST classification combined with proteinuria
      at biopsy could be one of the important early predictors for the renal survial
      outcomes in patients with IgAN.

PMID- 28439114
TI  - Material witness: Is this holy relic preserved?

PMID- 28439115
TI  - Porous materials: Look but don't touch.

PMID- 28439117
TI  - Spintronics: The molecular way.

PMID- 28439113
TI  - MicroRNA expression profiling defines the impact of electronic cigarettes on
      human airway epithelial cells.
AB  - While all forms of tobacco exposure have negative health effects, the
      significance of exposure to electronic cigarettes (eCig) is not fully understood.
      Here, we studied the global effects of eCig on the micro RNA (miRNA)
      transcriptome in human lung epithelial cells. Primary human bronchial epithelial
      (NHBE) cells differentiated at air-liquid interface were exposed to eCig liquid.
      Exposure of NHBE to any eCig liquid resulted in the induction of oxidative stress
      response genes including GCLM, GCLC, GPX2, NQO1 and HO-1. Vaporization of, and/or
      the presence of nicotine in, eCig liquid was associated with a greater response.
      We identified 578 miRNAs dysregulated by eCig exposure in NHBE, and 125 miRNA
      affected by vaporization of eCig liquid. Nicotine containing eCig vapor displayed
      the most profound effects upon miRNA expression. We selected 8 miRNAs (29A, 140,
      126, 374A, 26A-2, 147B, 941 and 589) for further study. We validated increased
      expression of multiple miRNAs, including miR126, following eCig exposure. We also
      found significant reduction in the expression of two miR126 target genes, MYC and
      MRGPRX3, following exposure. These data demonstrated that eCig exposure has
      profound effects upon gene expression in human lung epithelial cells, some of
      which are epigenetically programmed at the level of miRNA regulation.

PMID- 28439116
TI  - Activating the molecular spinterface.
AB  - The miniaturization trend in the semiconductor industry has led to the
      understanding that interfacial properties are crucial for device behaviour.
      Spintronics has not been alien to this trend, and phenomena such as preferential
      spin tunnelling, the spin-to-charge conversion due to the Rashba-Edelstein effect
      and the spin-momentum locking at the surface of topological insulators have
      arisen mainly from emergent interfacial properties, rather than the bulk of the
      constituent materials. In this Perspective we explore inorganic/molecular
      interfaces by looking closely at both sides of the interface. We describe recent
      developments and discuss the interface as an ideal platform for creating new spin
      effects. Finally, we outline possible technologies that can be generated thanks
      to the unique active tunability of molecular spinterfaces.

PMID- 28439118
TI  - White light-emitting diodes: Stabilizing colour and intensity.

PMID- 28439119
TI  - A molecular jigsaw puzzle.

PMID- 28439120
TI  - Erratum: Generation of subnanometric platinum with high stability during
      transformation of a 2D zeolite into 3D.

PMID- 28439122
TI  - Decidual vascular endothelial cells promote maternal-fetal immune tolerance by
      inducing regulatory T cells through canonical Notch1 signaling.

PMID- 28439121
TI  - Bioinformatic Approaches Including Predictive Metagenomic Profiling Reveal
      Characteristics of Bacterial Response to Petroleum Hydrocarbon Contamination in
      Diverse Environments.
AB  - Microbial remediation of oil polluted habitats remains one of the foremost
      methods for restoration of petroleum hydrocarbon contaminated environments. The
      development of effective bioremediation strategies however, require an extensive
      understanding of the resident microbiome of these habitats. Recent developments
      such as high-throughput sequencing has greatly facilitated the advancement of
      microbial ecological studies in oil polluted habitats. However, effective
      interpretation of biological characteristics from these large datasets remain a
      considerable challenge. In this study, we have implemented recently developed
      bioinformatic tools for analyzing 65 16S rRNA datasets from 12 diverse
      hydrocarbon polluted habitats to decipher metagenomic characteristics of the
      resident bacterial communities. Using metagenomes predicted from 16S rRNA gene
      sequences through PICRUSt, we have comprehensively described phylogenetic and
      functional compositions of these habitats and additionally inferred a multitude
      of metagenomic features including 255 taxa and 414 functional modules which can
      be used as biomarkers for effective distinction between the 12 oil polluted
      sites. Additionally, we show that significantly over-represented taxa often
      contribute to either or both, hydrocarbon degradation and additional important
      functions. Our findings reveal significant differences between hydrocarbon
      contaminated sites and establishes the importance of endemic factors in addition
      to petroleum hydrocarbons as driving factors for sculpting hydrocarbon
      contaminated bacteriomes.

PMID- 28439123
TI  - In Vivo Molecular Optical Coherence Tomography of Lymphatic Vessel Endothelial
      Hyaluronan Receptors.
AB  - Optical Coherence Tomography (OCT) imaging of living subjects offers increased
      depth of penetration while maintaining high spatial resolution when compared to
      other optical microscopy techniques. However, since most protein biomarkers do
      not exhibit inherent contrast detectable by OCT, exogenous contrast agents must
      be employed for imaging specific cellular biomarkers of interest. While a number
      of OCT contrast agents have been previously studied, demonstrations of molecular
      targeting with such agents in live animals have been historically challenging and
      notably limited in success. Here we demonstrate for the first time that
      microbeads (uBs) can be used as contrast agents to target cellular biomarkers in
      lymphatic vessels and can be detected by OCT using a phase variance algorithm.
      This molecular OCT method enables in vivo imaging of the expression profiles of
      lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a biomarker that
      plays crucial roles in inflammation and tumor metastasis. In vivo OCT imaging of
      LVYE-1 showed that the biomarker was significantly down-regulated during
      inflammation induced by acute contact hypersensitivity (CHS). Our work
      demonstrated a powerful molecular imaging tool that can be used for high
      resolution studies of lymphatic function and dynamics in models of inflammation,
      tumor development, and other lymphatic diseases.

PMID- 28439125
TI  - Electron-phonon coupling in topological surface states: The role of polar optical
      modes.
AB  - The use of topological edge states for spintronic applications could be severely
      hampered by limited lifetimes due to intrinsic many-body interactions, in
      particular electron-phonon coupling. Previous works to determine the intrinsic
      coupling strength did not provide a coherent answer. Here, the electron-phonon
      interaction in the metallic surface state of 3D topological insulators is revised
      within a first principles framework. For the archetypical cases of Bi2Se3 and
      Bi2Te3, we find an overall weak coupling constant of less than 0.15, but with a
      characteristic energy dependence. Derived electronic self-energies compare
      favorably with previous angle-resolved photoemission spectroscopy results. The
      prevailing coupling is carried by optical modes of polar character, which is
      weakly screened by the metallic surface state and can be reduced by doping into
      bulk bands. We do not find any indication of a strong coupling to the A1g mode or
      the presence of a Kohn anomaly in the surface phonon spectrum. The weak intrinsic
      electron-phonon coupling guarantees long-lived quasiparticles at elevated
      temperatures.

PMID- 28439124
TI  - Characterisation of a cell-free synthesised G-protein coupled receptor.
AB  - G-protein coupled receptors are the largest family of integral membrane proteins
      found within the human genome. They function as receptors and modulators to a
      wide range of ligands and responses which are crucial for human health. GPCR
      study, specifically the investigation of structure and interaction to cognate
      ligands, is of high priority. Limitations for structural study can be traced in
      part, to obtaining suitable quantities of recombinant protein. We sought to
      address the limitations of traditional recombinant technologies by utilising an
      Escherichia coli based cell-free protein synthesis (CFPS) approach for production
      of a thermostable neurotensin receptor 1 (en2NTS1). Initial results were
      promising, with a high amount (up to 2 mg/mL) of en2NTS1 produced, that had
      attained correct secondary structure. Meanwhile, concurrent experiments indicated
      that CFPS produced en2NTS1 showed non-competitive binding to the peptide ligand
      neurotensin8-13 when compared to E. coli produced en2NTS1. 1H-13C HMQC SOFAST NMR
      spectra were indicative of disrupted tertiary structure for CFPS produced 13CH3
      methionine labelled en2NTS1. The results obtained, indicate CFPS produced en2NTS1
      is not forming a discrete tertiary structure and that further development of the
      CFPS technique needs to be carried out.

PMID- 28439126
TI  - Necrotrophic growth of periodontopathogens is a novel virulence factor in oral
      biofilms.
AB  - The oral use of antimicrobial agents embedded in toothpastes and mouth rinses
      results in an oral microbial massacre with high amounts of dead bacteria in close
      proximity to few surviving bacteria. It was hypothesized that this provides the
      surviving pathogenic bacteria a large amount of dead microbial biomass as a
      nutritional source for growth (necrotrophy). This study demonstrated the
      necrotrophic growth of periodontal pathogens in the presence of different dead
      oral species. In addition, the presence of dead bacteria resulted in an outgrowth
      of several periodontal pathogens in complex multi-species biofilms. Additionally,
      upon contact with dead oral bacteria, virulence genes of P. intermedia and P.
      gingivalis were up-regulated (necrovirulence). This resulted in a more pronounced
      epithelial cytotoxicity (necrotoxicity). These findings indicate that presence of
      dead bacteria induce necrotrophy, necrovirulence and necrotoxicity in several
      oral pathogens.

PMID- 28439128
TI  - Culture Changes Needed to Implement ISMP IV Push Guidelines.

PMID- 28439127
TI  - Diversity and evolution of sex determination systems in terrestrial isopods.
AB  - Sex determination systems are highly variable in many taxa, sometimes even
      between closely related species. Yet the number and direction of transitions
      between these systems have seldom been characterized, and the underlying
      mechanisms are still poorly understood. Here we generated transcriptomes for 19
      species of terrestrial isopod crustaceans, many of which are infected by
      Wolbachia bacterial endosymbionts. Using 88 single-copy orthologous genes, we
      reconstructed a fully resolved and dated phylogeny of terrestrial isopods. An
      original approach involving crossings of sex-reversed individuals allowed us to
      characterize the heterogametic systems of five species (one XY/XX and four
      ZW/ZZ). Mapping of these and previously known heterogametic systems onto the
      terrestrial isopod phylogeny revealed between 3 and 13 transitions of sex
      determination systems during the evolution of these taxa, most frequently from
      female to male heterogamety. Our results support that WW individuals are viable
      in many species, suggesting sex chromosomes are at an incipient stage of their
      evolution. Together, these data are consistent with the hypothesis that nucleo
      cytoplasmic conflicts generated by Wolbachia endosymbionts triggered recurrent
      turnovers of sex determination systems in terrestrial isopods. They further
      establish terrestrial isopods as a model to study evolutionary transitions in sex
      determination systems and pave the way to molecularly characterize these systems.

PMID- 28439129
TI  - ISMP Medication Error Report Analysis: Betaine Anhydrous Versus Betaine
      Hydrochloride Look-Alike Generic Names Don't Give Zurampic Without Allopurinol
      Lantus Overdose Tied to Confusing Vial Label More on Lipid Rescue.
AB  - These medication errors have occurred in health care facilities at least once.
      They will happen again-perhaps where you work. Through education and alertness of
      personnel and procedural safeguards, they can be avoided. You should consider
      publishing accounts of errors in your newsletters and/or presenting them at your
      inservice training programs. Your assistance is required to continue this
      feature. The reports described here were received through the Institute for Safe
      Medication Practices (ISMP) Medication Errors Reporting Program. Any reports
      published by ISMP will be anonymous. Comments are also invited; the writers'
      names will be published if desired. ISMP may be contacted at the address shown
      below. Errors, close calls, or hazardous conditions may be reported directly to
      ISMP through the ISMPWeb site (www.ismp.org), by calling 800-FAIL-SAFE, or via e
      mail at ismpinfo@ismp.org. ISMP guarantees the confidentiality and security of
      the information received and respects reporters' wishes as to the level of detail
      included in publications.

PMID- 28439130
TI  - ISMP Adverse Drug Reactions.
AB  - The purpose of this feature is to heighten awareness of specific adverse drug
      reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to
      the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If
      you have reported an interesting, preventable ADR to MedWatch, please consider
      sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside
      Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail:
      mmancano@temple.edu). Your report will be published anonymously unless otherwise
      requested. This feature is provided by the Institute for Safe Medication
      Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple
      University School of Pharmacy. ISMP is an FDA MedWatch partner.

PMID- 28439131
TI  - Compliance with Updated Sepsis Bundles to Meet New Sepsis Core Measure in a
      Tertiary Care Hospital.
AB  - Background: The updated Surviving Sepsis Campaign care bundles are associated
      with improved outcomes in patients with sepsis, yet adherence to the bundles
      remains inconsistent. The Centers for Medicare & Medicaid Services has adopted
      similar care bundles as a core measure that went into effect with October 1, 2015
      discharges. Objective: The aim of this study was to assess bundle compliance,
      length of stay (LOS), and in-hospital mortality before and after introduction of
      the new sepsis core measure. Methods: A retrospective cohort study was conducted
      in 158 patients with a diagnosis of severe sepsis or septic shock from April 2015
      to February 2016. The before group (n = 48) consisted of sequential patients
      discharged from April 1, 2015 to September 30, 2015 (prior to core measure
      implementation), and the after group (n = 110) consisted of sequential patients
      discharged from October 1, 2015 to February 29, 2016 (after core measure
      implementation). Results: Significant improvement was seen in the after group
      compared to the before group for bundle compliance with the 3-hour (66.4% vs
      31.3%; p < 0.01) and 6-hour (75.5% vs 41.7%; p < 0.01) components and the overall
      core measure (51.8% vs 16.7%; p < 0.01). In-hospital mortality was lower in the
      after group compared to the before group (14.5% vs 27.1%; p = 0.05), but this
      difference was not statistically significant. There was no significant difference
      in LOS. Conclusions: The study found a significant increase in compliance with
      the sepsis care bundles since the implementation of this core measure. Increased
      adherence to the care bundles may improve in-hospital survival.

PMID- 28439132
TI  - Idelalisib and Rituximab Regimen.
AB  - The complexity of cancer chemotherapy requires pharmacists be familiar with the
      complicated regimens and highly toxic agents used. This column reviews various
      issues related to preparation, dispensing, and administration of antineoplastic
      therapy, and the agents, both commercially available and investigational, used to
      treat malignant diseases. Questions or suggestions for topics should be addressed
      to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201
      Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J.
      Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology
      Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander
      Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net. The information
      presented in this review is based on published data and clinical expertise and
      includes information not included in the product labeling. Incorporation of such
      published data provides a more robust assessment of the drugs and assists
      pharmacists in evaluation of orders for off-label use of these agents.

PMID- 28439133
TI  - Importance of Pharmacy Involvement in the Treatment of Sepsis.
AB  - Purpose: A review of the impact of pharmacists on appropriate medication
      selection, timing of administration, and as members of a multidisciplinary sepsis
      response team. Summary: Early goal-directed therapy (EGDT), currently recommended
      by the 2013 Surviving Sepsis Campaign guidelines for the management of patients
      with sepsis, includes the administration of appropriate antibiotics in patients
      with septic shock within the first hour. Multidisciplinary teams containing
      pharmacists have been shown to decrease time to antibiotic delivery, time to
      antibiotic administration, and patient mortality. The pharmacist can act as a
      drug information resource, expedite the medication verification and procurement
      process, and offer suggestions on how to better manage the patients. Pharmacists
      are often consulted for dosing and antibiotic selection recommendations for
      patients with sepsis, but they can also help increase the appropriateness of
      antibiotics selected. Additional recommendations and interventions made by
      pharmacists include fluid management and vasopressor facilitation for the more
      severe patients. A sepsis management team that included a pharmacist increased
      the number of patients receiving appropriate antibiotics within the first hour by
      as much as 22-fold. Another study has demonstrated that intensive care units with
      a pharmacist are associated with a 4% decrease in sepsis patient mortality
      compared to those without a pharmacist. Conclusion: Multidisciplinary teams
      containing pharmacists have been shown to decrease time to administration of
      antibiotics, increase appropriate selection of medications, and decrease
      mortality; they may also decrease overall health care costs.

PMID- 28439134
TI  - Pharmacy Dashboard: An Innovative Process for Pharmacy Workload and Productivity.
AB  - Background: Innovative approaches, including LEAN systems and dashboards, to
      enhance pharmacy production continue to evolve in a cost and safety conscious
      health care environment. Furthermore, implementing and evaluating the
      effectiveness of these novel methods continues to be challenging for pharmacies.
      Objective: To describe a comprehensive, real-time pharmacy dashboard that
      incorporated LEAN methodologies and evaluate its utilization in an inpatient
      Central Intravenous Additives Services (CIVAS) pharmacy. Methods: Long Beach
      Memorial Hospital (462 adult beds) and Miller Children's and Women's Hospital of
      Long Beach (combined 324 beds) are tertiary not-for-profit, community-based
      hospitals that are served by one CIVAS pharmacy. Metrics to evaluate the
      effectiveness of CIVAS were developed and implemented on a dashboard in real-time
      from March 2013 to March 2014. Results: The metrics that were designed and
      implemented to evaluate the effectiveness of CIVAS were quality and value,
      financial resilience, and the department's people and culture. Using a dashboard
      that integrated these metrics, the accuracy of manufacturing defect-free products
      was >=99.9%, indicating excellent quality and value of CIVAS. The metric for
      financial resilience demonstrated a cost savings of $78,000 annually within
      pharmacy by eliminating the outsourcing of products. People and value metrics on
      the dashboard focused on standard work, with an overall 94.6% compliance to the
      workflow. Conclusion: A unique dashboard that incorporated metrics to monitor 3
      important areas was successfully implemented to improve the effectiveness of
      CIVAS pharmacy. These metrics helped pharmacy to monitor progress in real-time,
      allowing attainment of production goals and fostering continuous quality
      improvement through LEAN work.

PMID- 28439135
TI  - Assessment of Direct Oral Anticoagulant Prescribing and Monitoring Pre- and Post
      Implementation of a Pharmacy Protocol at a Community Teaching Hospital.
AB  - Background: Direct oral anticoagulants (DOACs) have become popular alternatives
      to vitamin K antagonists for the treatment and prevention of thromboembolic
      diseases; however, there are limited data regarding the appropriate use of DOACs
      in clinical practice. To ensure safety and efficacy of these medications, it is
      important that decisions regarding their use in patients rely on the available
      evidence. Objective: The purpose of this study was to evaluate the
      appropriateness of DOAC prescribing in adult patients before and after the
      implementation of a pharmacist-driven DOAC protocol. Methods: Data were collected
      on adult patients admitted to a community teaching hospital who received DOAC
      therapy for at least 2 days between January and March 2015 (pre-intervention
      group) and between January and March 2016 (post-intervention group). These data
      were analyzed to measure inappropriately prescribed DOACs, defined based on DOAC
      indication, renal function, drug interactions, and other pertinent patient
      specific factors. Prior to the start of data collection for the post-intervention
      group, a pharmacist-driven protocol was developed and implemented. DOAC education
      was provided to pharmacists, including an evidence-based prescribing table to
      guide appropriate DOAC therapy. Comparisons were made between the pre
      intervention and post-intervention groups to determine the impact of the
      pharmacist-driven service on appropriate DOAC prescribing. Results: Fifty
      patients were analyzed in the pre-intervention group compared with 85 patients in
      the post-intervention group, with a total of 333 and 816 doses administered,
      respectively. Of the total doses administered, 32.4% were considered
      inappropriate in the pre-intervention group compared with 13.8% in the post
      intervention group (adjusted odds ratio [OR], 0.42, 95% CI, 0.19-0.96; p =
      0.039). Conclusions: Implementing a pharmacist-driven DOAC service significantly
      improved appropriate prescribing of these agents. Provider education regarding
      DOAC use is essential to further increase appropriate prescribing of DOACs,
      optimize patients' therapy, and prevent adverse drug events.

PMID- 28439137
TI  - Compatibility of Ceftazidime-Avibactam, Ceftolozane-Tazobactam, and Piperacillin
      Tazobactam with Vancomycin in Dextrose 5% in Water.
AB  - Objectives: The compatibility of vancomycin with existing and novel beta
      lactam/beta-lactamase inhibitors at clinically relevant concentrations in 5%
      dextrose in water has not been fully explored to date. Methods: Vancomycin
      concentrations tested ranged from 5 to 20 mg/mL. Ceftazidime-avibactam was tested
      at 8, 20, and 40 mg/mL, ceftolozane-tazobactam at 15 mg/mL, and piperacillin
      tazobactam at 28 mg/mL. Compatibility of drug admixtures were tested via both
      simulated and actual y-site infusion. For the simulated y-site compatibility
      assessment, 1:1 mixtures of each respective drug were analyzed over 24 hours.
      Actual y-site infusion followed a 4-hour extended-infusion protocol, with
      aliquots tested hourly for 4 hours. At all time points, the compatibility of each
      admixture was determined using 6 different methods: visual, microscopic, Tyndall
      beam, nephelometric, pH, and microbiologic bioassay assessment. If any admixture
      failed any one of these 6 assays, it was considered incompatible. Any combination
      deemed incompatible was filtered through a 0.22 MUm filter and reanalyzed to
      assess impact of particle size. Results: There were no differences in
      compatibility categorizations between simulated and actual y-site infusion. There
      were no changes in compatibility over the time course of any experiment.
      Ceftazidime-avibactam at 8 mg/mL was incompatible with vancomycin at 5 mg/mL. The
      maximum compatible vancomycin concentrations were 5 mg/mL and 10 mg/mL with 20
      and 40 mg/mL of ceftazidime-avibactam, respectively. Ceftolozane-tazobactam 15
      mg/mL was compatible with vancomycin concentrations up to 10 mg/mL. The maximum
      compatible vancomycin concentration with piperacillin-tazobactam 28 mg/mL was 5
      mg/mL. None of the beta-lactam/beta-lactamase inhibitors tested were compatible
      with 15 or 20 mg/mL of vancomycin. None of the admixtures considered incompatible
      by other methods displayed any decrease in antimicrobial activity as assessed by
      bioassay. After filtration, all admixtures originally deemed incompatible
      maintained their visual turbidity and microscopic particulate matter.
      Conclusions: Ceftazidime-avibactam prepared at the lowest concentration
      recommended in the package insert is incompatible with vancomycin. Ceftolozane
      tazobactam did not display incompatibility until vancomycin concentrations above
      10 mg/mL were tested. Piperacillin-tazobactam at a typical extended-infusion
      concentration is compatible with vancomycin in D5W. To our knowledge, this is the
      first study to assess compatibility of antibiotic admixtures via direct
      measurement of antimicrobial activity. The lack of any decrement in antibacterial
      activity of any apparently incompatible admixture and maintenance of
      incompatibility after passage through a 0.22 MUm filter may suggest a lack of
      clinically relevant adverse effects when co-administered. Future compatibility
      studies should incorporate appropriate methods to accurately assess both efficacy
      and safety of co-administered drug products.

PMID- 28439136
TI  - Clinical Feasibility of Monitoring Enoxaparin Anti-Xa Concentrations: Are We
      Getting It Right?
AB  - Background: Anti-Xa monitoring is utilized to measure the extent of
      anticoagulation in certain patient populations receiving enoxaparin. It is
      essential to accurately obtain this pharmacodynamic marker for safe and effective
      anticoagulation management. Objectives: To determine the frequency of correctly
      drawn anti-Xa concentrations in accordance with predefined institutional criteria
      and to determine the number of dose adjustments implemented based on incorrectly
      drawn anti-Xa concentrations. Methods: This was a retrospective, single-center,
      cohort study among adult patients who received treatment doses of enoxaparin with
      measured anti-Xa concentrations. Patients were excluded if they were pregnant, on
      hemodialysis, or received prophylactic dosing. Anti-Xa levels were defined as
      correctly measured if they were drawn 3 to 5 hours after the dose during steady
      state concentrations. Descriptive statistics were performed and analyzed via SPSS
      software. Results: Overall, 203 patients were reviewed and 59 patients with 74
      anti-Xa levels were included. The majority of anti-Xa levels (57/74; 77%) were
      drawn incorrectly and often resulted in collection of repeat anti-Xa samples.
      There were 12 documented dose adjustments and approximately 42% (5/12) were based
      on incorrectly drawn anti-Xa levels. Anti-Xa levels were within target range
      approximately 45% of the time. Conclusions: Enoxaparin anti-Xa concentrations are
      frequently drawn incorrectly and dose adjustments are often performed based on
      these unsupported anti-Xa levels. This may present a potential risk to compromise
      patient safety.

PMID- 28439138
TI  - Bezlotoxumab.
AB  - Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well
      documented monographs on drugs that are newly released or are in late phase 3
      trials. The monographs are targeted to Pharmacy & Therapeutics Committees.
      Subscribers also receive monthly 1-page summary monographs on agents that are
      useful for agendas and pharmacy/nursing in-services. A comprehensive target drug
      utilization evaluation/medication use evaluation (DUE/MUE) is also provided each
      month. With a subscription, the monographs are available online to subscribers.
      Monographs can be customized to meet the needs of a facility. Through the
      cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in
      this column. For more information about The Formulary Monograph Service, contact
      Wolters Kluwer customer service at 866-397-3433. The March 2017 monograph topics
      are crisaborole, insulin degludec/liraglutide, inclusion glargine/lixisenatide,
      nusimersen, and rucaparib. The MUE is on insulin GLP-1 combo.

PMID- 28439139
TI  - Approvals, Submission, and Important Labeling Changes for US Marketed
      Pharmaceuticals.
AB  - This monthly feature will help readers keep current on new drug, new indications,
      dosage forms and safety-related changes in labeling or use. Efforts have been
      made to assure the accuracy of this information; however, if there are any
      questions, please let us know at jgeneral@ku.edu.

PMID- 28439140
TI  - Are Pharmacists Participating in Postdischarge Patient Reminders?
AB  - In this column, we are making a short revisit to the technology that can assist
      in satisfaction of Meaningful Use criteria and can assist health systems that are
      increasing their population health initiatives to help improve outcomes while
      containing costs.

PMID- 28439141
TI  - Application of Suzuki-Miyaura and Buchwald-Hartwig Cross-coupling Reactions to
      the Preparation of Substituted 1,2,4-Benzotriazine 1-Oxides Related to the
      Antitumor Agent Tirapazamine.
AB  - Many 1,2,4-benzotriazine 1,4-dioxides display the ability to selectively kill the
      oxygen-poor cells found in solid tumors. As a result, there is a desire for
      synthetic routes that afford access to substituted 1,2,4-benzotriazine 1-oxides
      that can be used as direct precursors in the synthesis of 1,2,4-benzotriazine 1,4
      dioxides. Here we describe the use of Suzuki-Miyaura and Buchwald-Hartwig cross
      coupling reactions for the construction of various 1,2,4-benzotriazine 1-oxide
      analogs bearing substituents at the 3-, 6-, and 7-positions.

PMID- 28439142
TI  - Amine vs. carboxylic acid protonation in ortho-, meta-, and para-aminobenzoic
      acid: An IRMPD spectroscopy study.
AB  - Infrared multiple photon dissociation (IRMPD) spectroscopy and computational
      chemistry are applied to the ortho-, meta-, and para- positional isomers of
      aminobenzoic acid to investigate whether the amine or the carboxylic acid are the
      favored sites of proton attachment in the gas phase. The NH and OH stretching
      modes yield distinct patterns that establish the carboxylic acid as the site of
      protonation in para-aminobenzoic acid, as opposed to the amine group in ortho-
      and meta-aminobenzoic acid, in agreement with computed thermochemistries. The
      trends for para- and meta-substitutions can be rationalized simplistically by
      inductive effects and resonant stabilization, and will be discussed in light of
      computed charge distributions based from electrostatic potentials. In ortho
      aminobenzoic acid, the close proximity of the amine and acid groups allow a
      simultaneous interaction of the proton with both groups, thus stabilizing and
      delocalizing the charge more effectively, and compensating for some of the
      resonance stabilization effects.

PMID- 28439143
TI  - Dynamics of Urban Informal Labor Supply in the United States.
AB  - OBJECTIVE: This study provides the first panel data estimates of informal work in
      the US and explores relationships between informal- and regular-sector
      participation among urban parents of young children. METHODS: I examine
      determinants of informal-sector participation in five waves of data from the
      Fragile Families and Child Wellbeing Study using probit, pooled Tobit, and fixed
      effects OLS models. RESULTS: Approximately 53 percent of urban fathers and 32
      percent of urban mothers with young children pursue informal work over a nine
      year period. Informal work most often occurs in conjunction with regular work.
      Workers who work in both sectors in the same year are more likely to be non
      minority race, higher education (mothers only), own credit cards, and work in
      skilled white- or blue-collar occupations. Workers who ever participate in only
      the informal sector are more likely to be younger, to have health limitations,
      and to have never worked in the regular sector. Informal participation spells are
      shorter than regular-sector participation spells and are associated with changes
      in regular-sector participation and occupation but not most other life events.
      CONCLUSION: Consistent with past work, informal work among parents of young
      children is widespread across socioeconomic groups. Transitions in and out of the
      informal sector are strongly related to changes in regular-sector employment and
      occupation. The results suggest that regular-sector participation provides access
      to informal work opportunities.

PMID- 28439144
TI  - Vocabulary size and auditory word recognition in preschool children.
AB  - Recognizing familiar words quickly and accurately facilitates learning new words,
      as well as other aspects of language acquisition. This study used the visual
      world paradigm with semantic and phonological competitors to study lexical
      processing efficiency in 2-5 year-old children. Experiment 1 found this paradigm
      was sensitive to vocabulary-size differences. Experiment 2 included a more
      diverse group of children who were tested in their native dialect (either African
      American English or Mainstream American English). No effect of stimulus dialect
      was observed,. Results showed that vocabulary size was a better predictor of eye
      gaze patterns than maternal education, but that maternal education level had a
      moderating effect; as maternal education level increased, vocabulary size was
      less predictive of lexical processing efficiency.

PMID- 28439145
TI  - Revisiting the choice of the driving temperature for eddy covariance CO2 flux
      partitioning.
AB  - So-called CO2 flux partitioning algorithms are widely used to partition the net
      ecosystem CO2 exchange into the two component fluxes, gross primary productivity
      and ecosystem respiration. Common CO2 flux partitioning algorithms conceptualize
      ecosystem respiration to originate from a single source, requiring the choice of
      a corresponding driving temperature. Using a conceptual dual-source respiration
      model, consisting of an above- and a below-ground respiration source each driven
      by a corresponding temperature, we demonstrate that the typical phase shift
      between air and soil temperature gives rise to a hysteresis relationship between
      ecosystem respiration and temperature. The hysteresis proceeds in a clockwise
      fashion if soil temperature is used to drive ecosystem respiration, while a
      counter-clockwise response is observed when ecosystem respiration is related to
      air temperature. As a consequence, nighttime ecosystem respiration is smaller
      than daytime ecosystem respiration when referenced to soil temperature, while the
      reverse is true for air temperature. We confirm these qualitative modelling
      results using measurements of day and night ecosystem respiration made with
      opaque chambers in a short-statured mountain grassland. Inferring daytime from
      nighttime ecosystem respiration or vice versa, as attempted by CO2 flux
      partitioning algorithms, using a single-source respiration model is thus an
      oversimplification resulting in biased estimates of ecosystem respiration. We
      discuss the likely magnitude of the bias, options for minimizing it and conclude
      by emphasizing that the systematic uncertainty of gross primary productivity and
      ecosystem respiration inferred through CO2 flux partitioning needs to be better
      quantified and reported.

PMID- 28439146
TI  - Domestic and International Climate Migration from Rural Mexico.
AB  - Evidence is increasing that climate change and variability may influence human
      migration patterns. However, there is less agreement regarding the type of
      migration streams most strongly impacted. This study tests whether climate change
      more strongly impacted international compared to domestic migration from rural
      Mexico during 1986-99. We employ eight temperature and precipitation-based
      climate change indices linked to detailed migration histories obtained from the
      Mexican Migration Project. Results from multilevel discrete-time event-history
      models challenge the assumption that climate-related migration will be
      predominantly short distance and domestic, but instead show that climate change
      more strongly impacted international moves from rural Mexico. The stronger
      climate impact on international migration may be explained by the self-insurance
      function of international migration, the presence of strong migrant networks, and
      climate-related changes in wage difference. While a warming in temperature
      increased international outmigration, higher levels of precipitation declined the
      odds of an international move.

PMID- 28439147
TI  - A Semi-parametric Transformation Frailty Model for Semi-competing Risks Survival
      Data.
AB  - In the analysis of semi-competing risks data interest lies in estimation and
      inference with respect to a so-called non-terminal event, the observation of
      which is subject to a terminal event. Multi-state models are commonly used to
      analyse such data, with covariate effects on the transition/intensity functions
      typically specified via the Cox model and dependence between the non-terminal and
      terminal events specified, in part, by a unit-specific shared frailty term. To
      ensure identifiability, the frailties are typically assumed to arise from a
      parametric distribution, specifically a Gamma distribution with mean 1.0 and
      variance, say, sigma2. When the frailty distribution is misspecified, however,
      the resulting estimator is not guaranteed to be consistent, with the extent of
      asymptotic bias depending on the discrepancy between the assumed and true frailty
      distributions. In this paper, we propose a novel class of transformation models
      for semi-competing risks analysis that permit the non-parametric specification of
      the frailty distribution. To ensure identifiability, the class restricts to
      parametric specifications of the transformation and the error distribution; the
      latter are flexible, however, and cover a broad range of possible specifications.
      We also derive the semi-parametric efficient score under the complete data
      setting and propose a non-parametric score imputation method to handle right
      censoring; consistency and asymptotic normality of the resulting estimators is
      derived and small-sample operating characteristics evaluated via simulation.
      Although the proposed semi-parametric transformation model and non-parametric
      score imputation method are motivated by the analysis of semi-competing risks
      data, they are broadly applicable to any analysis of multivariate time-to-event
      outcomes in which a unit-specific shared frailty is used to account for
      correlation. Finally, the proposed model and estimation procedures are applied to
      a study of hospital readmission among patients diagnosed with pancreatic cancer.

PMID- 28439148
TI  - Do You Have Anything to Hide? Infidelity-Related Behaviors on Social Media Sites
      and Marital Satisfaction.
AB  - Social media provides one route to behaviors that may be potentially harmful to
      romantic relationships, such as communicating with alternative partners, which
      can sometimes create relationship conflict, breakups, or divorce. Limited
      empirical evidence exists concerning social media infidelity-related behaviors
      and marital relationships. This study examined whether married/cohabiting
      individuals are using social media sites to engage in online infidelity-related
      behaviors and to what extent this related to relationship satisfaction,
      ambivalence, and relational attachment characteristics as reported by 338
      married/cohabiting individuals from 176 families. Only a small percentage of
      married/cohabiting couples reported engaging in social media infidelity-related
      behaviors; however, more engagement in infidelity-related behaviors on social
      media was significantly related to lower relationship satisfaction, higher
      relationship ambivalence, and greater attachment avoidance and anxiety in both
      women and men. Additionally, attachment anxiety and gender interacted with
      relationship satisfaction in predicting online infidelity-related behaviors when
      controlling for other variables. Implications are discussed.

PMID- 28439149
TI  - Refinement and Preliminary Testing of an Imagery-Based Program to Improve Coping
      and Performance and Prevent Trauma among Urban Police Officers.
AB  - Police officers are regularly exposed to traumatic critical incidents. The
      substantial mental, behavioral, and social costs of police trauma indicate a
      substantial need for prevention. We have refined and enhanced a previously tested
      Swedish program to the harsh conditions of U.S. inner cities. The program was
      designed to strengthen resilience during stressful encounters and teach methods
      of coping after exposure, thereby preventing the emergence of maladaptive
      symptoms and behaviors with adverse effects on professionalism. In an
      uncontrolled demonstration project, junior officers were trained by senior
      officers to engage in imaginal rehearsal of specific dangerous situations while
      incorporating optimal police tactics and healthy emotional reactions. A class of
      32 officers in the police academy engaged in the program, and they and the
      trainers reported high satisfaction with it. After their first year of field
      work, 22 officers were reassessed. Compared to pre-training, these officers
      showed significant increases in the use of positive reframing and humor and
      significant reductions in anxiety and alcohol use over the year. Trauma symptoms
      did not increase. These results offer preliminary evidence for the feasibility
      and effectiveness of this trauma prevention program for new police officers.

PMID- 28439150
TI  - Effect of Pet Dogs on Children's Perceived Stress and Cortisol Stress Response.
AB  - The present study tested whether pet dogs have stress-buffering effects for
      children during a validated laboratory-based protocol, the Trier Social Stress
      Test for Children (TSST-C). Participants were 101 children aged 7-12 years with
      their primary caregivers and pet dogs. Children were randomly assigned in the
      TSST-C to a pet present condition or one of two comparison conditions: parent
      present or no support figure present. Baseline, response, and recovery indices of
      perceived stress and cortisol levels were computed based on children's self
      reported feelings of stress and salivary cortisol. Results indicated that in the
      alone (no social support) condition, children showed the expected rise for both
      perceived stress and cortisol response to stress. Pet dog presence significantly
      buffered the perceived stress response in comparison to children in the alone and
      parent present conditions. No main condition effect was observed for cortisol;
      however, for children experiencing the stressor with their pet present, lower
      cortisol response to stress was associated with more child-initiated petting and
      less dog proximity-seeking behavior. The results support the notion that pet dogs
      can provide socio-emotional benefits for children via stress buffering.

PMID- 28439151
TI  - Sinus Grafts: Science and Techniques-Then and Now.
AB  - INTRODUCTION: Sinus lifts have been around for more than four decades now, and
      the amount of changes that we have seen in techniques and armamentarium coupled
      with the advent of newer materials is worth taking note of. MATERIALS AND
      METHODS: A complete review of the literature was done since the advent of ways
      and means to augment the posterior maxilla with a run through of various
      advantages and disadvantages of the same. CONCLUSION: In conclusion, we can say
      that this procedure is today very predictable and offers clinicians a possibility
      to rehabilitate the posterior maxilla with implant-based solutions.

PMID- 28439152
TI  - Intraosseous Leiomyoma of the Mandible: A Case Report of the Rare Entity and
      Review of Literature.
AB  - INTRODUCTION: Leiomyoma is a rare tumor of smooth muscle origin with a very low
      incidence in the maxillofacial region. Intraosseous occurrence of oral leiomyoma
      is even rare with involvement of mandible followed by maxilla. AIM: The purpose
      of this paper is to present a case of intraosseous leiomyoma of the left
      mandibular angle region with the review of literature describing this rare
      entity. The paper also highlights the need to include this entity in differential
      diagnoses of jaw lesions. MATERIAL AND METHOD: An extensive search of literature
      was carried out on the Medline-Pubmed and Google Scholar database using the
      keywords leiomyoma, maxilla, mandible, oral and palate to thoroughly search and
      collect all the reported cases of intraosseous leiomyoma. RESULT: To the best of
      our knowledge till date only 22 cases of intraosseous leiomyoma have been
      reported in the maxillomandibular region we represent the 23rd case of the
      intraosseous leiomyoma in a 36 year old male patient. CONCLUSION: Though uncommon
      but it is known to occur in the jaws therefore intraosseous leiomyoma should be
      included in the list of differential diagnoses of radiolucent lesion of mandible
      and maxilla.

PMID- 28439153
TI  - Supraclavicular Metastases from Distant Primary Solid Tumours: A Retrospective
      Study of 41 Years.
AB  - OBJECTIVES: Approximately 1 % of all malignant solid tumours of the head and neck
      area are metastases from primary tumours beneath the clavicles. The aim of this
      study was to analyse the distribution of primary tumours since meta-analyses
      might have been biased due to the usually extraordinary character of case
      reports. MATERIALS AND METHODS: All patient files from 1970 to 2012 from the Oral
      and Maxillofacial Surgery unit at a University Hospital were analysed regarding
      the existence of metastases to the head and neck area from distant primaries.
      RESULTS: Of the seventy-three patients 18 had breast cancers (25 %), 9 melanomas
      (12 %), 8 tumours of the kidneys and 8 of the lungs (each 12 %), 3 colon cancers
      (6 %), 2 prostate cancers (3 %), 2 Ewing sarcomas (3 %), and 1 each of
      liposarcoma, esophagus, rectum, hepatocellular carcinoma, vulva, ovarian and
      testicular cancer. In 15 cases, a cancer of unknown primary was diagnosed. In 28
      cases the metastasis was the initial sign of the malignant disease. Skeletal
      metastasis occurred in 37 cases and a soft tissue metastasis in 36 patients.
      CONCLUSION: The different primaries seem to metastasize in different frequencies
      to the head and neck area. The relatively common prostate cancer rarely seems to
      produce metastases in the head and neck area compared to cancers arising in the
      kidneys. In case of a malignant tumour of unknown primary, osseous metastases
      most often are caused by breast or lung cancer or renal cell carcinoma. Soft
      tissue metastases are most often caused by breast cancer.

PMID- 28439154
TI  - Analysis of Survival Rates Following Primary Surgery of 178 Consecutive Patients
      with Oral Cancer in a Large District General Hospital.
AB  - PURPOSE: The aim of this study is to present the survival rates in patients
      treated for oral cancer with primary surgery in a large district general
      hospital. We discuss the influence of the most significant prognostic factors on
      survival and compare our results with larger centres specializing in the
      management of oral cancer. METHODS: All patients diagnosed with oral cancer from
      1995 to 2006 and were treated in the Department had their details entered
      prospectively onto a computerized database. Demographic details of patients, type
      of treatment, pathological stage of tumor (TNM), local and regional recurrence
      rate, overall survival, disease specific survival and incidence of involved
      margins were recorded and calculated. RESULTS: Of the 178 patients, 96 (54 %)
      were alive and free of oral cancer 5 years after surgery. Forty-four patients
      died of oral cancer (24.7 %) but 38 (21.3 %) died of other causes. The overall
      survival rate after primary surgery in relation to stage was: I 84 %, II 71 %,
      III 36 % and IV 28 %. DISCUSSION: As almost half of our patients presented with
      advanced cancer and had discouraging survival rates, we emphasize the need for
      early recognition of the disease. Advanced disease signifies difficulty in
      obtaining clear margins which actually indicates a higher recurrence rate. 25 %
      of our patients died of oral cancer within 5 years of surgery which highlights
      the poor prognosis that recurrence carries after treatment. Effective educational
      campaign with purpose to raise oral cancer awareness and earlier referral may
      result in improvement of survival.

PMID- 28439156
TI  - Diclofenac Transdermal Patch: A Potential Ingress to Maxillofacial Surgery.
AB  - PURPOSE: To evaluate the analgesic efficacy of a diclofenac transdermal patch
      with diclofenac intra muscular injection in the immediate postoperative period in
      patients undergoing major oral surgical procedures. MATERIALS AND METHODS:
      Subjects who underwent bijaw surgeries for surgical correction of various
      dentofacial deformities were included. Sixty such patients who belonged to the
      above entity were randomly categorized into two groups from Jan 2012-Aug 2015.
      Group A (study group) received a single dose of 100 mg transdermal diclofenac
      patch, Group B (control group) received 75 mg intramuscular diclofenac and
      tramadol HCl 2 mg/kg body wt was used as rescue analgesic in the immediate post
      operative phase. The analgesic efficacy of the drugs are evaluated on periodic
      patient's perception of pain in the immediate postoperative phase of 2nd, 6th,
      12th, 24th and 48 hours. RESULTS: The mean VAS score in Group A was 2, mean
      duration of analgesia was 16 h 9 min, and in Group B the mean VAS score was 4,
      duration of analgesia was 8 h and 4 min. Tramadol HCl was given as rescue
      analgesia in 22 % (6) of patients belonging to Group A. None of the patients from
      both the groups reported local complications. CONCLUSION: A noninvasive
      application of a single dose of 100 mg transdermal diclofenac patch is more
      effective than intramuscular diclofenac (75 mg) in the immediate post operative
      phase, without any significant side-effects is a novel ingress into the field of
      oral and maxillofacial surgery for post operative pain management.

PMID- 28439155
TI  - Extracranial Trigeminal Schwannomas: A Retrospective Analysis.
AB  - OBJECTIVE: To analyse the clinic-radiological features and treatment outcome of
      extracranial trigeminal schwannomas. METHOD: Medical records and radiographs of
      patients treated, from January 2011 to December 2013, for neurogenic tumors were
      retrospectively reviewed. Extracranial schwannomas other than those of trigeminal
      nerve were also excluded. A number of parameters, including the patient's age,
      gender, site, clinical features, radiographic features, histologic variants and
      treatment provided as well as any associated complications were recorded and
      analysed. RESULT: A total of 5 patients met the inclusion criteria. The patients
      were males, aged 16-56 years. All the schwannomas appear to originate from the
      terminal branches of trigeminal nerve. CONCLUSION: Long standing asymptomatic
      swelling of cheek should include trigeminal schwannomas as the differential
      diagnosis. The diagnosis though confirmed by the histologic examination but can
      also be made on the basis of MRI finding. Neural function can be preserved by
      meticulous surgery.

PMID- 28439157
TI  - Re-Assessment of Coronoid as a Graft for Condylar Reconstruction in TMJ Ankylosis
      Patients: A Prospective Study and Literature Review.
AB  - INTRODUCTION: Treatment for TMJ ankylosis aims at restoring joint function,
      improving the patient's aesthetic appearance and quality of life and preventing
      re-ankylosis. To rebuild a structurally and functionally satisfactory neocondyle
      is a challenging problem. Aim of this study is to re-assess the coronoid as a
      graft for condyle reconstruction. MATERIALS AND METHODS: Twenty patients of TMJ
      ankylosis without involvement of the coronoid process in ankylotic mass, coming
      in age group elder than 14 years were selected for the study over a period 3
      years from 2011 to 2014. Clinical examination, radiographs, and photographs were
      used postoperatively to evaluate the grafts and TMJ function. After
      osteoarthrectomy coronoid process was detached and fixed with a 4 hole L-shaped
      titanium miniplate to form neo condyle. RESULT: No donor site morbidity was
      observed as reported with other autogenous grafts. Satisfactory mouth opening was
      observed during follow up period with mean mouth opening 37.33 +/- 4.20 mm except
      one case which required graft removal due to postoperative infection.
      Radiographically moderate amount of resorption of grafted coronoid process was
      observed in nearly all the cases however satisfactory mandibular function and
      occlusion was observed.

PMID- 28439158
TI  - Trigemino-Cardiac Reflex: A Phenomenon Neglected in Maxillofacial Surgery?
AB  - BACKGROUND: Trigemino-cardiac reflex is a physiologic response of the body to
      pressure effects in the region of distribution of the trigeminal nerve. Oral and
      maxillofacial surgical procedures can induce the development of this reflex,
      which leads to significant changes in the heart rate and sinus rhythms. This
      study intends to evaluate the effects of this reflex in patients with facial
      fractures and its subsequent management. PATIENTS AND METHODS: A total of thirty
      seven patients with facial fractures who reported to the Department of Oral and
      Maxillofacial Surgery at Basaveswar Teaching and General Hospital, Gulbarga
      during a period from July 2015-March 2016 were considered for the study. RESULTS:
      A male preponderance is observed with the most susceptible age group being 21-30
      years. Twenty-three patients sustained mid-facial fractures alone, nine patients
      had isolated mandible fractures and five patients had fractures of both the mid
      face and mandible. A relative bradycardia was observed in the patients with mid
      facial trauma, both at the time of presentation and also during the surgical
      reduction of midfacial fractures which improved after completion of procedure in
      most of the patients. However, in two patients, the bradycardia progressed to a
      cardiac asystole during midface manipulation which required immediate halt of the
      procedure and intravenous administration of atropine. CONCLUSION:
      Trigeminocardiac reflex though physiologic, which usually tends to subside
      without complications is not to be neglected in the surgeries of the
      maxillofacial skeleton. A propensity for unforeseen complications due to this
      reflex has to be avoided by meticulous monitoring of the ECG.

PMID- 28439159
TI  - A Randomized Controlled Study Comparing Efficacy of Classical and Gow-Gates
      Technique for Providing Anesthesia During Surgical Removal of Impacted Mandibular
      Third Molar: A Split Mouth Design.
AB  - INTRODUCTION: Reliable profound mandibular block anesthesia is questionable when
      depositing the anesthetic solution at the lingula. The Gow-Gates technique is an
      useful alternative to the classical inferior alveolar nerve block and the
      incidence of unsuccessful anesthesia may be as high as classical technique. The
      aim of this study is to compare the clinical efficacy, degree of patient
      acceptability, advantages, disadvantages and limitations of the classical and Gow
      Gates techniques for providing anesthesia in patients undergoing bilateral
      symmetrical surgical removal of impacted mandibular third molar under local
      anesthesia. MATERIAL AND METHODS: The split mouth design study was conducted on
      100 patients aged between 20 to 40 years undergoing surgical removal of bilateral
      symmetrical impacted mandibular third molar performed by the same maxillofacial
      surgeon. 2 ml of 2 % lignocaine hydrochloride with 1:80,000 adrenaline was used
      as a standard local anesthetic solution in all the cases. By using four-digit
      numbers from a random number table, either Gow-Gates or classical inferior
      alveolar nerve block were randomly assigned to either left or right sides in each
      patient. The injections were administered by another surgeon who was blinded to
      the experiment. The patient was assessed for Pain experienced during injection,
      frequency of positive aspirations, Onset and duration of anesthesia and Nerves
      anesthetized. RESULTS: Results were statistically analyzed by Mann-Whitney and
      chi square test. A 'P' value of less than 0.05 was considered for statistical
      significance. Higher mean pain during injection was recorded in classical group,
      was found to be statistically significant. No significant association was
      observed between aspiration and the groups. Higher mean onset of anesthesia was
      recorded in Gow-gates group, was found to be statistically significant. Higher
      mean duration of anesthesia was recorded in Gow-gates group, was not
      statistically significant. Higher success rate was recorded in Gow-gates group
      and was statistically significant. CONCLUSION: If we ignore delayed onset of
      anesthesia of Gow gates technique, it is found to be more reliable, beneficial
      and have higher success rate than classical inferior alveolar nerve block
      technique.

PMID- 28439160
TI  - Ranula Decompression Using Stitch and Stab Method: The Aluko Technique.
AB  - BACKGROUND: A ranula is a cystic lesion in the floor of the mouth, formed either
      as a retention cyst or pseudocyst as a result of extravasation of mucus in the
      surrounding tissue. It may be treated by micro-marsupialization, marsupialization
      or excision of lesion with or without the associated salivary gland.
      Marsupialization is usually achieved by cutting a slit and thereafter stitching
      the edges such that the epithelium of the exterior becomes continuous with that
      of the interior of a cyst. A stitch-and-stab technique of achieving patency of
      the created slit of marsupialized ranula is hereby presented. METHOD: A stitch
      and stab technique using four parallel consecutive strokes of the needle with
      attached polyglactin 910 suture material in alternately opposing directions was
      employed in treatment of 31 consecutive ranula patients. RESULTS: 100 % success
      was achieved using this technique in 31 ranulas. CONCLUSION: This stitch-and-stab
      technique for marsupialization has proven to be very successful. It is
      recommended for use by the general medical community, as it requires the
      Clinician to possess only minimal surgical skills. Bartholin's cyst can be so
      treated.

PMID- 28439161
TI  - Three-Dimensional Analysis of the Anatomical Characteristics and Dimensions of
      the Nasopalatine Canal Using Cone Beam Computed Tomography.
AB  - AIM: Placement of implants in the maxillary anterior region needs to be preceded
      by careful analysis of the area as in addition to the functional aspect the
      esthetic outcome is of prime importance. This descriptive study evaluated
      anatomical characteristics and dimensions of the nasopalatine canal (NC) from
      coronal, sagittal and axial aspects using cone beam computed tomography (CBCT)
      giving it a three dimensional analytical approach. Also the dimensions of the
      corresponding buccal bone plate (BBP) of the alveolar process were evaluated.
      Additionally, the influence of age and gender on these characteristics was also
      analyzed. METHODS: A total of 81-CBCT scans of patients with one or no upper
      central incisors present were selected. Sagittal slices were used for
      measurements of the NC and BBP and to evaluate shape of the NC. Coronal slices
      were used to assess NC shape and axial slices to assess number of incisive
      foramina and foramina of Stenson. RESULTS: The most prevalent canal shape was:
      cylindrical (48.14 %) in sagittal aspect; Y-type (49.38 %) in coronal aspect; and
      one incisive foramen with two Stenson's foramina [1-(2-5)] (60.49 %) in axial
      aspect. Mean NC length was 11.13 +/- 3.23 mm; statistically significant
      differences were detected between genders (p < 0.001). Mean nasopalatine angle
      was 69.32 degrees  +/- 7.70. Mean BBP length was 17.12 +/- 3.97 mm and mean BBP
      width was 5.71 +/- 1.29 mm, significant differences were detected between genders
      (p < 0.001). CONCLUSION: The current study demonstrates variability of the NC in
      terms of anatomical characteristics and dimensions; hence, a thorough CBCT
      analysis is highly recommended for better surgical outcomes and to reduce the
      post-operative complications in implant dentistry.

PMID- 28439162
TI  - Evaluating the Effect of Minimizing Screws on Stabilization of Symphysis
      Mandibular Fracture by 3D Finite Element Analysis.
AB  - PURPOSE: The objective of this work is to integrate structural optimization and
      reliability concepts into mini-plate fixation strategy used in symphysis
      mandibular fractures. The structural reliability levels are next estimated when
      considering a single failure mode and multiple failure modes. PATIENTS AND
      METHODS: A 3-dimensional finite element model is developed in order to evaluate
      the ability of reducing the negative effect due to the stabilization of the
      fracture. Topology optimization process is considered in the conceptual design
      stage to predict possible fixation layouts. In the detailed design stage,
      suitable mini-plates are selected taking into account the resulting topology and
      different anatomical considerations. Several muscle forces are considered in
      order to obtain realistic predictions. Since some muscles can be cut or harmed
      during the surgery and cannot operate at its maximum capacity, there is a strong
      motivation to introduce the loading uncertainties in order to obtain reliable
      designs. The structural reliability is carried out for a single failure mode and
      multiple failure modes. RESULTS: The different results are validated with a
      clinical case of a male patient with symphysis fracture. In this case while use
      of the upper plate fixation with four holes, only two screws were applied to
      protect adjacent vital structure. This behavior does not affect the stability of
      the fracture. CONCLUSION: The proposed strategy to optimize bone plates leads to
      fewer complications and second surgeries, less patient discomfort, and shorter
      time of healing.

PMID- 28439163
TI  - Superolateral Dislocation of Bilateral Intact Mandibular Condyles: A Rare Case
      Series.
AB  - BACKGROUND AND PURPOSE: The dislocation of mandibular condyle is a clinical
      condition in which the head of condyle has been displaced out of the glenoid
      fossa. Complete dislocation of the mandibular condyle can occur in anterior,
      posterior, lateral and superior direction. Among these dislocations, bilateral
      superolateral dislocation of mandibular condyles is quite rare and often
      misdiagnosed. Because of its rare occurrence and unusual clinical course, the
      best treatment is debatable. PATIENTS AND METHOD: We present the first case
      series of true bilateral superolateral dislocation of intact mandibular condyles
      (Type 2B) without fracturing the Zygomatic arch, associated with symphysis
      fracture. CONCLUSION: This article intends to provide information regarding the
      possible biomechanics and management of bilateral superolateral dislocation of
      mandibular condyles associated with symphysis fracture.

PMID- 28439165
TI  - Single Injection Technique Prolotherapy for Hypermobility Disorders of TMJ Using
      25 % Dextrose: A Clinical Study.
AB  - INTRODUCTION: Hypermobility disorders of the Temporomandibular joint (TMJ) can be
      treated by both conservative and surgical approaches. Conservative approaches
      should be considered as first line treatment for such disorders. Prolotherapy
      with 25 % dextrose being injected into the posterior pericapsular tissues is one
      such treatment modality with favorable outcomes. AIM: To study the efficacy of
      single injection of 25 % dextrose in pericapsular tissues in the management of
      hypermobility joint disorders of TMJ as first line treatment. PATIENTS AND
      METHODS: We have studied a total of 23 patients suffering from either chronic
      recurrent dislocation or subluxation of the TMJ who were treated with the single
      injection technique prolotherapy with 25 % dextrose into the pericapsular tissues
      along with auriculotemporal nerve block and found encouraging results. RESULTS:
      Overall success rate in our study was 91.3 % (21/23) with a minimum follow up
      period of 13.9 months. Number of successfully treated patients requiring one
      injection was 7 (30.4 %), two injections was 8 (34.7 %) and requiring three
      injections was 6 (26.1 %). There were no permanent complications. CONCLUSION:
      Hence the use of 25 % dextrose as a proliferant to treat hypermobilty disorders
      of the TMJ is recommended by us as a first line treatment option as it is safe,
      economical and an easy procedure associated with minimal morbidity.

PMID- 28439164
TI  - Use of T.M.J. Disc as a Soft Tissue Interpositional Graft Material for Functional
      Rehabilitation of Ankylosed T.M. Joint.
AB  - INTRODUCTION: Many surgical techniques have been described for the treatment of
      TMJ ankylosis, but no strategy has been uniformly agreed upon underscoring the
      difficulty of the problem. Despite new guidelines and updated methods, treating
      patients with TMJ Ankylosis remains a challenge as the incidence of recurrence
      after treatment is soaring. This study exemplifies our experience in using an
      unsullied method to treat TMJ Ankylosis to restore the structure of TMJ in
      conjunction with convalescing secondary maxillofacial deformity. MATERIALS AND
      METHODS: A total of 56 cases of unilateral bony TMJ ankylosis were included in
      the study, and postoperative results of T.M.J disc as a soft tissue interposition
      graft was evaluated. The operative protocol comprised of (1) resection of
      ankylotic mass, (2) intraoral ipsilateral coronoidectomy or contralateral
      coronoidectomy when needed, (4) interpositioning disc as soft tissue graft, (5)
      interposing and fixing sternoclavicular or costocondral graft with lag screws and
      (6) early mobilization, aggressive physiotherapy. RESULTS: The study assessed
      patients with regular follow-up checks for a period of 3 years. The average
      preoperative mouth opening was found to be 5.46 mm (range 2-10 mm). Mean post
      operative mouth opening was 33.05 mm (range 24-43 mm), while 3 years post
      operative mouth opening (mean) was 39.75 mm. No cases of reankylosis were
      reported during this period suggesting it as a viable and satisfactory approach.
      CONCLUSION: The use of TMJ disc as a soft tissue interpositional graft material
      is an effectual method for functional rehabilitation of ankylosis cases and
      serves as an effective means of preventing recurrence.

PMID- 28439166
TI  - End Stage Renal Disease: Not a Contraindication for Minor Oral Surgery-Protocol
      for the Management of Oral Surgery patients with ESRD on Hemodialysis.
AB  - OBJECTIVE: To describe a safe and effective protocol for the management of
      patients with end stage renal disease (ESRD) undergoing minor oral surgery.
      SUBJECTS AND METHODS: A prospective cohort study was conducted on all patients
      with ESRD who were referred for dental consultation. A definite protocol was
      designed in consultation with the nephrologist to minimize the risk of bleeding
      and wound healing complications during and after the minor surgical procedures.
      36 patients consented for the protocol to be followed while 4 patients did not
      comply with the protocol and in 2 cases the protocol could be followed. The intra
      operative, post operative bleeding, and the wound healing were assessed in these
      patients. RESULTS: 36 patients had uneventful extractions as the blood pressure
      was brought down to pre hypertensive stage following the protocol. 4 patients who
      did not comply with the protocol had episodes of bleeding in the post operative
      period. There were two special scenarios where additional precautions had to be
      taken have been discussed. The wound healing was satisfactory in all these
      patients. CONCLUSION: The protocol discussed in this article helps us provide
      safe minor oral surgical treatment in patients with ESRD.

PMID- 28439167
TI  - Comparative Evaluation of C-Reactive Protein and WBC Count in Fascial Space
      Infections of Odontogenic Origin.
AB  - PURPOSE: To assess efficacy of C-reactive protein levels as monitoring tools for
      patients with fascial space infections of odontogenic origin. MATERIAL AND
      METHOD: A randomized prospective study was conducted on 20 patients suffering
      from fascial space infection of odontogenic origin, in the department of Oral and
      Maxillofacial Surgery Bharati Vidyapeeth dental college and hospital, Pune,
      Patients between 18 and 60 years of age of both the sexes were selected. All
      patients were treated and observed by the same surgeon. Patient's venous blood
      sample was collected pre-operatively and on 2nd and 5th post-operative days for
      evaluation of WBC count and C-reactive protein (CRP). All patients were
      encouraged for strict follow-up protocol. RESULT: Where the results of WBC count
      and CRP when compared it was seen that the mean values of WBC were normal in 15
      cases and abnormal in 5 cases on day 0, day 2 and day 5; whereas the mean values
      of CRP were abnormal on day 0 and day 2 and were within normal limit on day 5 in
      all cases. CONCLUSION: The findings of this prospective analysis indicate that
      White blood cells and C-reactive protein are effective markers for determining
      severity of infection, efficacy of treatment regime for patients with fascial
      space infections of odontogenic origin. Thus the markers also help in making
      treatment of patients with fascial space infections of odontogenic origin more
      cost effective and they also help protecting patients from side effects of excess
      drugs usage. Thus we conclude that CRP should be incorporated as monitoring tools
      for managing patients with fascial space infections of odontogenic origin.

PMID- 28439168
TI  - Ocular Injuries in Patients of Zygomatico-Complex (ZMC) Fractures.
AB  - PURPOSE: Mid face injuries commonly destroy the integrity of the orbital
      skeleton, and are frequently complicated by injury to the eye, ranging between
      2.7 and 90.6 % as reported in literature. The eye injuries range from simple
      subconjunctival haemorrhage to globe rupture. The paper aims to study the types
      of ocular injuries in patients with ZMC fractures. PATIENTS AND METHODS: A study
      of 67 patients, who had sustained facial trauma sufficient to lead to a facial
      bone fracture, was undertaken in the department of Oral and Maxillofacial
      Surgery, Govt Dental College, Srinagar from 2008 to 2014 and the patients
      received a comprehensive examination by an ophthalmologist within 1 week of
      injury. All the patients sustaining confirmed ZMC fracture were examined by an
      ophthalmologist for any associated ocular injury. A thorough ophthalmologic
      examination included assessment of visual acuity, pupillary reactivity, anterior
      and posterior segment examination and extraocular motility. The variables
      reviewed included patient's gender, mechanism of injury, visual acuity, pupillary
      reactivity, extra ocular motility, presence or absence of diplopia, ocular and
      orbital findings, and intraorbital hypoesthesia. RESULTS: The most common
      etiology of trauma was RTA (64.1 %), followed by falls (14.9 %) in our study. In
      our study 83.5 % of the patients were males. Minor ocular injuries such as
      subconjunctival haemorrhage and corneal injury accounted for most of the cases.
      Subconjunctival haemorrhage was the most common injury, present in 86.5 % of the
      cases. Hyphema was present 13.4 %, vitreous haemorrhage 2.98 %, retinal
      haemorrhage 1.49 %, corneal abrasion 4.47 %, mydriasis 1.49 %, choroidal rupture
      5.97 %, retinal detachment 2.98 %, decreased visual activity 13.4 %, retinal tear
      and angle recession was present 7.46 % times. CONCLUSION: ZMC fractures are
      associated with higher incidence of ocular injuries. The incidence of traumatic
      optic neuropathy and other ocular injuries warrants a prompt ophthalmologic
      examination of all patients with ZMC fractures as quickly as possible to prevent
      morbidity.

PMID- 28439169
TI  - The Cortical Boundary Line as a Guide for Incisor Re-positioning with Anterior
      Segmental Osteotomies.
AB  - Anterior alveolar anatomical constraints involving presurgical orthodontic
      incisor repositioning are often unrecognized and overlooked during orthodontic
      surgical treatment planning. A clear discrimination of this cortical limitation
      is invaluable during the planning stage as it permits the consideration of
      alternative approaches like the anterior maxillary osteotomy for effecting the
      required incisor movement. A simple reference line termed the "Cortical Boundary
      Line" is introduced to facilitate the clinical translation of this information
      and through suitable case illustrations, the construction of the reference line
      using the conventional lateral cephalometric radiograph and its usefulness as an
      adjunct in aiding decisions on orthodontic incisor decompensation is highlighted.

PMID- 28439170
TI  - Non Calcifying Type of Calcifying Epithelial Odontogenic Tumor: An Unusual Case
      Report with Special Emphasis on Histogenesis of Calcifications.
AB  - Calcifying epithelial odontogenic tumour also known as Pindborg tumour, is a rare
      benign odontogenic neoplasm of locally aggressive behavior. It is thought to
      arise from the epithelial element of the enamel origin which are reminiscent of
      the cells in the stratum intermedium layer of enamel organ in tooth development.
      The tumour is characterized histologically by the presence of polygonal
      epithelial cells, calcifications and eosinophilic deposits resembling amyloid.
      Non-calcifying epithelial odontogenic tumours are very rare and unusual. Only
      five cases have been reported in the English literature till date. Here, we
      present an additional case of non calcifying type along with a review of
      previously reported cases. It has a much lower recurrence and malignant
      transformation rate.

PMID- 28439171
TI  - Lingual Based Four Cornered Flap for Third Molar Surgery.
AB  - PURPOSE: The aim of this prospective randomized clinical study was to compare the
      efficacy of lingual based four cornered flap with the commonly used triangular
      flap for impacted third molar surgery. METHODS: Ten patients with bilateral
      impacted third molars were randomly treated under local anaesthesia, one side
      with triangular flap and single layer closure (with 3-0 silk) and other side by
      raising lingual based four cornered flap and double layer closure, subcutaneously
      with 5-0 vicryl and mucosa with 3-0 silk. All patients were operated by single
      surgeon (A. Rai) and suture removal was done after 7 days. RESULTS: Healing by
      primary intension takes place when lingual flap and double layer suturing was
      done, also the patients had less pain, swelling and alveolar osteitis. The
      visibility was excellent with lingual flap and pocket formation distal to second
      molar was also less. The only drawback with lingual flap is that it required
      little less time in comparison to triangular flap. CONCLUSION: The lingual based
      four cornered flap is better than the triangular flap.

PMID- 28439172
TI  - Management of Chronic Recurrent Dislocation of Temporomandibular Joint Using 'U'
      Shaped Graft: A New Restrictive Technique.
AB  - BACKGROUND: Numerous procedures have been described for the treatment of chronic
      recurrent dislocation of the temporo-mandibular joint (TMJ), either in the form
      of enhancement or restriction of the condylar movement, with their obvious merits
      and demerits. MATERIALS AND METHOD: We present a new technique of using U shaped
      iliac bone graft to restrict the condylar movement and its advantages over the
      conventional techniques.We have used this technique successfully in 8 cases where
      Dautrey's procedure had failed with follow up period of 2 years. RESULTS: No
      patient complained of recurrent dislocation postoperatively. CONCLUSION: This a
      very simple and effective technique where other procedures have failed.

PMID- 28439173
TI  - Surgical Correction of Brodie Bite in Adults: A Novel Surgical Splint.
AB  - INTRODUCTION: The incidence of telescopic bite is a rare occurrence. Brodie bite
      malocclusions manifest with severe skeletal and dental transverse, sagittal and
      vertical problems. MATERIALS AND METHODS: A patient presenting with a telescopic
      bite and mandibular retrognathism was treated by orthognathic approach. A unique
      surgical splint was used as an aid in performing the maxillary constriction and
      segmental osteotomy. CONCLUSION: The telescopic bite was corrected successfully
      and occlusal rehabilitation was achieved.

PMID- 28439174
TI  - Advantage of Kilner's Modification of Mouth Gag in Reference to Simple Technique
      Overcoming a Persistent Problem in Cleft Palate Repair.

PMID- 28439175
TI  - Foreword: Big Data and Its Application in Health Disparities Research.
AB  - The articles presented in this special issue advance the conversation by
      describing the current efforts, findings and concerns related to Big Data and
      health disparities. They offer important recommendations and perspectives to
      consider when designing systems that can usefully leverage Big Data to reduce
      health disparities. We hope that ongoing Big Data efforts can build on these
      contributions to advance the conversation, address our embedded assumptions, and
      identify levers for action to reduce health care disparities.

PMID- 28439176
TI  - Commentary: In the Rising Era of Big Data, Small Steps are Key.
AB  - Big Data may be useful to identify and perhaps ameliorate health disparities.
      However, over reliance on the power on Big Data can potentially cause harm. When
      assessing health disparities, the use of Big Data should be limited to hypothesis
      generation.

PMID- 28439177
TI  - Racial and Ethnic Differences in a Linkage with the National Death Index.
AB  - OBJECTIVES: Differences in the availability of a Social Security Number (SSN) by
      race/ethnicity could affect the ability to link with death certificate data in
      passive follow-up studies and possibly bias mortality disparities reported with
      linked data. Using 1989-2009 National Health Interview Survey (NHIS) data linked
      with the National Death Index (NDI) through 2011, we compared the availability of
      a SSN by race/ethnicity, estimated the percent of links likely missed due to lack
      of SSNs, and assessed if these estimated missed links affect race/ethnicity
      disparities reported in the NHIS-linked mortality data. METHODS: We used
      preventive fraction methods based on race/ethnicity-specific Cox proportional
      hazards models of the relationship between availability of SSN and mortality
      based on observed links, adjusted for survey year, sex, age, respondent-rated
      health, education, and US nativity. RESULTS: Availability of a SSN and observed
      percent linked were significantly lower for Hispanic and Asian/Pacific Islander
      (PI) participants compared with White non-Hispanic participants. We estimated
      that more than 18% of expected links were missed due to lack of SSNs among
      Hispanic and Asian/PI participants compared with about 10% among White non
      Hispanic participants. However, correcting the observed links for expected missed
      links appeared to only have a modest impact on mortality disparities by
      race/ethnicity. CONCLUSIONS: Researchers conducting analyses of mortality
      disparities using the NDI or other linked death records, need to be cognizant of
      the potential for differential linkage to contribute to their results.

PMID- 28439178
TI  - Hispanic Residential Isolation, ADHD Diagnosis and Stimulant Treatment among
      Medicaid-Insured Youth.
AB  - OBJECTIVE: This study aimed to evaluate a conceptual framework that assessed the
      effect of Hispanic residential isolation on Attention Deficit Hyperactivity
      Disorder (ADHD) health service utilization among 2.2 million publicly insured
      youth. DESIGN: Cross-sectional. SETTING: Medicaid administrative claims data for
      ambulatory care services from a US Pacific state linked with US census data.
      PARTICIPANTS: Youth, aged 2-17 years, continuously enrolled in 2009. MAIN OUTCOME
      MEASURES: The percent annual prevalence and odds of ADHD diagnosis and stimulant
      use according to two measures of racial/ethnic residential isolation: 1) the
      county-level Hispanic isolation index (HI) defined as the population density of
      Hispanic residents in relation to other racial/ethnic groups in a county (<.5; .5
      .64; >=.65); and 2) the proportion of Hispanic residents in a ZIP code tabulation
      area (<25%; 25%-50%; >50%). RESULTS: Among the 47,364 youth with a clinician
      reported ADHD diagnosis, 60% received a stimulant treatment (N = 28,334). As the
      county level HI increased, Hispanic residents of ethnically isolated locales were
      significantly less likely to receive an ADHD diagnosis (adjusted odds ratio
      [AOR]=.92 [95% CI=.88-.96]) and stimulant use (AOR=.61 [95% CI=.59-.64]) compared
      with Hispanic youth in less isolated areas. At the ZIP code level, a similar
      pattern of reduced ADHD diagnosis (AOR=.81 [95% CI=.77-.86]) and reduced
      stimulant use (AOR=.65 [95% CI=.61-.69]) was observed as Hispanic residential
      isolation increased from the least isolated to the most isolated ZIP code areas.
      CONCLUSIONS: These findings highlight the opportunity for Big Data to advance
      mental health research on strategies to reduce racial/ethnic health disparities,
      particularly for poor and vulnerable youth. Further exploration of racial/ethnic
      residential isolation in other large data sources is needed to guide future
      policy development and to target culturally sensitive interventions.

PMID- 28439180
TI  - Enhancing Diversity in Biomedical Data Science.
AB  - The gap in educational attainment separating underrepresented minorities from
      Whites and Asians remains wide. Such a gap has significant impact on workforce
      diversity and inclusion among cross-cutting Biomedical Data Science (BDS)
      research, which presents great opportunities as well as major challenges for
      addressing health disparities. This article provides a brief description of the
      newly established National Institutes of Health Big Data to Knowledge (BD2K)
      diversity initiatives at four universities: California State University, Monterey
      Bay; Fisk University; University of Puerto Rico, Rio Piedras Campus; and
      California State University, Fullerton. We emphasize three main barriers to BDS
      careers (ie, preparation, exposure, and access to resources) experienced among
      those pioneer programs and recommendations for possible solutions (ie, early and
      proactive mentoring, enriched research experience, and data science curriculum
      development). The diversity disparities in BDS demonstrate the need for
      educators, researchers, and funding agencies to support evidence-based practices
      that will lead to the diversification of the BDS workforce.

PMID- 28439179
TI  - Big Data Science: Opportunities and Challenges to Address Minority Health and
      Health Disparities in the 21st Century.
AB  - Addressing minority health and health disparities has been a missing piece of the
      puzzle in Big Data science. This article focuses on three priority opportunities
      that Big Data science may offer to the reduction of health and health care
      disparities. One opportunity is to incorporate standardized information on
      demographic and social determinants in electronic health records in order to
      target ways to improve quality of care for the most disadvantaged populations
      over time. A second opportunity is to enhance public health surveillance by
      linking geographical variables and social determinants of health for
      geographically defined populations to clinical data and health outcomes. Third
      and most importantly, Big Data science may lead to a better understanding of the
      etiology of health disparities and understanding of minority health in order to
      guide intervention development. However, the promise of Big Data needs to be
      considered in light of significant challenges that threaten to widen health
      disparities. Care must be taken to incorporate diverse populations to realize the
      potential benefits. Specific recommendations include investing in data collection
      on small sample populations, building a diverse workforce pipeline for data
      science, actively seeking to reduce digital divides, developing novel ways to
      assure digital data privacy for small populations, and promoting widespread data
      sharing to benefit under-resourced minority-serving institutions and minority
      researchers. With deliberate efforts, Big Data presents a dramatic opportunity
      for reducing health disparities but without active engagement, it risks further
      widening them.

PMID- 28439181
TI  - Perspective: Hope for Health Equity.
AB  - Times like these test the soul. We are now working for health equity in a time of
      overt, aggressive opposition. Yet, hope in the face of overwhelming obstacles is
      the force that has driven most of the world's progress toward equity and justice.
      Operationalizing real-world hope requires an affirmative vision, an expectation
      of success, broad coalitions taking action cohesively, and frequent measures of
      collective impact to drive rapid-cycle improvement.

PMID- 28439182
TI  - Perspective: POTUS Trump's Executive Orders - Implications for Immigrants and
      Health Care.
AB  - The United States, under new executive orders proposed by its 45th president, may
      quickly lose its greatness in serving Emma Lazarus' untimely portrait of
      immigrants and refugees as "the tired, poor and huddled masses yearning to
      breathe free." After years of progress in improving health care access to
      underserved populations, new executive orders threaten our nation's advancements
      in health equity. Within this perspective, we offer examples on how these actions
      may result in damaging impacts on patients, families, communities and the health
      care workforce. We add our voices to a myriad of national leaders who are
      advocating for the preservation of the Affordable Care Act (ACA) and the
      protection of immigrants, including Deferred Action for Childhood Arrivals
      (DACA).

PMID- 28439183
TI  - Race-Ethnic Disparities in Hospital Arrival Time after Ischemic Stroke.
AB  - OBJECTIVE: Conflicting reports exist about hospital arrival time after stroke
      onset in Hispanics compared with African Americans and Caucasians. Our current
      study investigates race-ethnic disparities in hospital arrival times after stroke
      onset. METHODS: We performed a retrospective analysis of hospital arrival times
      in Hispanic, African American, and Caucasian acute ischemic stroke patients
      (N=1790) presenting to a tertiary-care hospital in the Bronx, New York. A
      multivariable logistic regression model was used to identify the association
      between race-ethnicity and hospital arrival time adjusting for age, sex,
      socioeconomic status (SES), NIH stroke scale (NIHSS), history of stroke,
      preferred language and transportation mode to the hospital. RESULTS: There were
      338 Caucasians, 662 Hispanics, and 790 African Americans in the cohort. Compared
      with Caucasians, African Americans and Hispanics were younger (P<.0001
      respectively), had lower SES (P<.001 respectively) and were less likely to use
      EMS (P=.003 and P=.001, respectively). A greater proportion of Hispanic and
      African American women had delayed hospital arrival times (>=3 hours) after onset
      of stroke symptoms compared with Caucasian women (74% of Hispanic, 72% of African
      American, and 59% of Caucasian women), but this difference between race
      ethnicities is no longer present after adjusting for socioeconomic status.
      Compared with Caucasian men, hospital arrival >=3 hours after symptom onset was
      more likely for African American men (OR 1.72, 95% CI:1.05-2.79) but not Hispanic
      men (OR .80, 95% CI .49-1.30). CONCLUSIONS: African American men and socially
      disadvantaged women delay in presenting to the hospital after stroke onset.
      Future research should focus on identifying the factors contributing to pre
      hospital delay among race-ethnic minorities.

PMID- 28439184
TI  - Systemic Inflammation and Viral Exposure among Young Mexican American Women:
      Nativity-Related Differences.
AB  - BACKGROUND: Factors contributing to elevated inflammation in racial/ethnic
      minority populations are not well understood. We examined the association of
      viral exposure with C-reactive protein (CRP) in young Mexican American women.
      METHODS AND RESULTS: Participants (N=1,141) were currently non-pregnant women of
      Mexican background, aged 18-39 years, from the cross-sectional National Health
      and Nutrition Examination Survey (NHANES) 1999-2010. Viral exposure was defined
      as seropositive status for hepatitis B, and herpes simplex types 1 and 2, and
      classified as seronegative, seropositive for any one agent, and seropositive for
      2 or 3 agents. The association of viral exposure with elevated CRP (3.01-10.00
      mg/L) varied by country of birth (P=.001). Among Mexico-born women, those
      seropositive for 2 or 3 agents had 3.79 times (95% CI: 1.28-11.27) and those
      seropositive for any one agent 2.56 times (95% CI: 1.12-5.86) the odds of
      elevated CRP compared with seronegative women, after adjustment for age, country
      of birth, household density, waist circumference, glycated hemoglobin, and total
      cholesterol. Among US-born women, the corresponding odds were OR: .32, 95% CI:
      .12-.86 and OR: .71, 95% CI .43-1.17. CONCLUSIONS: In Mexico-born Mexican
      American women, viral exposure is associated with higher odds of elevated CRP.

PMID- 28439185
TI  - "I don't have to explain, people understand": Acceptability and Cultural
      Relevance of a Mobile Health Lifestyle Intervention for Filipinos with Type 2
      Diabetes.
AB  - BACKGROUND: Filipino Americans have the highest risk for obesity-related type 2
      diabetes and related complications compared with all major Asian American
      subgroups. Identifying effective interventions to improve Filipino health
      outcomes are needed to reduce this health disparity. OBJECTIVE: To assess the
      acceptability and cultural relevance of the PilAm Go4Health program - a
      culturally adapted mobile health weight-loss lifestyle intervention including
      virtual social networking for Filipino Americans with type 2 diabetes. DESIGN
      SETTING PARTICIPANTS: Qualitative semi-structured post-program interviews
      explored perceptions of 45 Filipino Americans with type 2 diabetes in Northern
      California regarding their perceptions of the acceptability and cultural
      relevance of PilAm Go4Health. Participants' mean age was 57.6 years. Sixty-seven
      interviews were recorded, transcribed, and thematically analyzed by four
      independent coders. RESULTS: Over half (n=26, 57.8%) of the respondents found
      that a culturally tailored intervention program enhanced their engagement. All
      (n=45) of the respondents felt that mobile health technology promoted their self
      efficacy. A majority of the respondents (n=29, 64.4%) expressed that they
      progressed from despair to self-efficacy as a result of their participation in
      the intervention. More than one-fourth of the participants (n=13, 28.8%)
      discussed that the intervention needed further cultural tailoring. CONCLUSIONS:
      Overall, PilAm Go4Health - a mobile health weight-loss lifestyle intervention -
      was acceptable and culturally relevant for Filipino Americans with type 2
      diabetes. Findings may help inform clinician and researchers on effective
      intervention strategies for diabetes self-management when designing interventions
      for diverse populations.

PMID- 28439186
TI  - Impact of Distress Reduction on Behavioral Correlates and A1C in African American
      Women with Uncontrolled Type 2 Diabetes: Results from EMPOWER.
AB  - OBJECTIVE: Symptoms of emotional distress related to diabetes have been
      associated with inadequate self-care behaviors, medication non-adherence, and
      poor glycemic control that may predispose patients to premature death. African
      American women, in whom diabetes is more common and social support is often
      insufficient, may be at particularly high risk. The objective of this study was
      to examine the impact of lowering diabetes-related emotional distress on glycemic
      control and associated behavioral correlates in rural African American women with
      uncontrolled type 2 diabetes (T2D). DESIGN: Post-hoc analysis of prospective,
      randomized, controlled trial. SETTING: Rural communities in the southeastern
      United States. PATIENTS: 129 rural middle-aged African American women with
      uncontrolled type 2 diabetes (T2D)(A1C >= 7.0). PRIMARY INDEPENDENT VARIABLE:
      Diabetes-related distress. MAIN OUTCOME MEASURES: Changes from baseline to 12
      month follow-up in diabetes-related distress, and associated changes in
      medication adherence, self-care activities, self-efficacy, and glycemic control
      (A1C). RESULTS: Patients with a reduction in diabetes-related distress (n=79) had
      significantly greater improvement in A1C, medication adherence, self-care
      activities, and self-efficacy compared with those in whom diabetes distress
      worsened or was unchanged (n=50). Changes in distress were also significantly and
      inversely correlated with improvements in medication adherence, self-care
      activities, and self-efficacy. CONCLUSIONS: Among rural African American women,
      reductions in diabetes-related distress may be associated with lower A1C and
      improvements in self-efficacy, self-care behaviors, and medication adherence.

PMID- 28439187
TI  - Body Mass Index and Intensive Care Unit Outcomes in African American Patients.
AB  - PURPOSE: We sought to determine whether body mass index (BMI) is associated with
      worse intensive care unit (ICU) outcomes among Black patients. METHODS: Patients
      admitted to the medical ICU during 2012 were categorized into six BMI groups
      based on the World Health Organization criteria. ICU mortality, ICU and hospital
      length of stay (LOS), need for and duration of mechanical ventilation and organ
      failure rate were assessed. RESULTS: A total of 605 patients with mean age 58.9
      +/- 16.0 years were studied. Compared with those with normal BMI, obese patients
      had significant higher rates of hypertension, diabetes mellitus and obstructive
      sleep apnea diagnoses (P<.001 for all). A total of 100 (16.5%) patients died
      during their ICU stay. Obesity was not associated with increased odds of ICU
      mortality (OR=.58; 95% CI, .16-2.20). Moreover, improved survival was observed
      for class II obese patients (OR, .031; 95% CI, .001-.863). There were no
      differences in the need for and duration of mechanical ventilation between the
      BMI groups. However, ICU and hospital LOS were significantly longer in patients
      with obesity. CONCLUSION: Obesity was not associated with increased ICU
      mortality; however, obesity was associated with increased comorbid illness and
      with significant longer ICU and hospital length of stay.

PMID- 28439188
TI  - Next Generation Sequencing Reveals High Prevalence of BRCA1 and BRCA2 Variants of
      Unknown Significance in Early-Onset Breast Cancer in African American Women.
AB  - BACKGROUND: Variants of unknown significance (VUSs) have been identified in BRCA1
      and BRCA2 and account for the majority of all identified sequence alterations.
      Notably, VUSs occur disproportionately in people of African descent hampering
      breast cancer (BCa) management and prevention efforts in the population. Our
      study sought to identify and characterize mutations associated with increased
      risk of BCa at young age. METHODS: In our study, the spectrum of mutations in
      BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early
      age at onset breast cancer, with a family history of breast or cancer in general
      and/or with triple negative breast cancer. To improve the characterization of the
      BRCA1 and BRCA2 variants, bioinformatics tools were utilized to predict the
      potential function of each of the variants. RESULTS: Using next generation
      sequencing methods and in silico analysis of variants, a total of 197 BRCA1 and
      266 BRCA2 variants comprising 77 unique variants were identified in 31 patients.
      Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation
      (rs80359304; BRCA2 Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%)
      were benign, and 29 (37.7%) were VUSs. Genetic epidemiological approaches were
      used to determine the association with variant, haplotype, and phenotypes, such
      as age at diagnosis, family history of cancer and family history of breast
      cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966
      (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949
      (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log
      Additive models, respectively) and rs3765640 (P=.033 Log Additive model).
      Additionally, a haplotype composed of all 5 SNPs was found to be significantly
      associated with younger age at diagnosis using linear regression modeling
      (P=.023). Specifically, the haplotype containing all the variant alleles was
      associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14). CONCLUSIONS:
      Knowing a patient's BRCA mutation status is important for prevention and
      treatment decision-making. Improving the characterization of mutations will lead
      to better management, treatment, and BCa prevention efforts in African Americans
      who are disproportionately affected with aggressive BCa and may inform future
      precision medicine genomic-based clinical studies.

PMID- 28439189
TI  - Development and Evaluation of Two Abbreviated Questionnaires for Mentoring and
      Research Self-Efficacy.
AB  - OBJECTIVES: To reduce respondent burden for future evaluations of the National
      Heart, Lung, and Blood Institute-supported Programs to Increase Diversity Among
      Individuals Engaged in Health-Related Research (PRIDE), a mentored-research
      education program, we sought to shorten the 33-item Ragins and McFarlin Mentor
      Role Instrument (RMMRI), measuring mentor-role appraisals, and the 69-item
      Clinical Research Appraisal Inventory (CRAI), measuring research self-efficacy.
      METHODS: Three nationally recruited, junior-faculty cohorts attended two, annual
      2-3 week Summer Institutes (SI-1/SI-2: 2011/2012, 2012/2013, 2013/2014) at one of
      six PRIDE sites. Mentees completed the RMMRI two months after mentor assignment
      and the CRAI at baseline (pre-SI-1) and 6-month (mid-year) and 12-month (post-SI
      2) follow-up. Publications data obtained from Scopus in October 2015 were
      verified with mentees' curriculum vitae. The RMMRI and CRAI were shortened using
      an iterative process of principal-components analysis. The shortened measures
      were examined in association with each other (multiple linear regression) and
      with increase in publications (repeated-measures analysis of covariance).
      RESULTS: PRIDE enrolled 152 mentees (70% women; 60% Black, 35% Hispanic/Latino).
      Cronbach's alphas for the new 9-item RMMRI, 19-item CRAI, and four CRAI-19
      subscales were excellent. Controlling for baseline self-efficacy and cohort,
      RMMRI-9 scores were independently, positively associated with post-SI-2 scores on
      the CRAI-19 and three subscales (writing, study design/data analysis, and
      collaboration/grant preparation). Controlling for cohort, higher RMMRI-9 and post
      SI-2 CRAI-19 scores were each associated with greater increase in publications.
      CONCLUSIONS: The RMMRI-9 and CRAI-19 retained the excellent psychometric
      properties of the longer measures. Findings support use of the shortened measures
      in future evaluations of PRIDE.

PMID- 28439191
TI  - Complex Recovery: Understanding the Lives of Formerly Homeless Adults with
      Complex Needs.
AB  - OBJECTIVE: This report examines mental health recovery in a population neglected
      in the literature--formerly homeless adults with serious mental illness and co
      occurring substance abuse. The term 'complex recovery' is used to examine the
      onset and impact of various types of adversity over the life course. METHOD:
      Burawoy's extended case method was conducted on in-depth interviews with 74
      formerly homeless adults living in housing programs in New York City. Data
      included verbatim transcripts, interviewer feedback forms, and case summaries.
      RESULTS: Seven themes emerged: the longstanding influence of poverty, childhood
      hardship, social support and network depletion, substance abuse and recovery,
      unequal impact of gender differences, experiences of incarceration and fragmented
      service system. Structural as well as individual factors were found to comprise
      complex recovery. CONCLUSIONS: Complex recovery, which situates mental health
      recovery amidst homelessness and other forms of adversity, has implications for
      policies and practices designed to assist this vulnerable population.

PMID- 28439190
TI  - Review: Metabolic Syndrome in Black South African Women.
AB  - The prevalence of metabolic syndrome is increasing in African populations, and is
      particularly high in Black South African women (42%) vs women in the United
      Kingdom (23%) and the United States of America (36%). This population group is
      also known to have the highest prevalence of obesity in the sub-Saharan African
      region (42%), and consequently, a high risk of non-communicable diseases. In this
      article, we discuss factors (abdominal subcutaneous fat, visceral fat, lean mass,
      adiponectin, leptin, vitamin D, smoking and menopausal status) that have been
      investigated for their possible association with metabolic syndrome in African
      women, and discuss some recommendations for management of the syndrome. In
      particular, the infrastructural development of HIV/AIDS clinics in South Africa
      provides an ideal integrated platform to cater to the treatment needs of patients
      with multiple chronic morbidities.

PMID- 28439192
TI  - Bedside Vein Mapping for Conduit Size in Coronary Artery Bypass Surgery.
AB  - BACKGROUND AND OBJECTIVES: The greater saphenous vein has been used in coronary
      artery bypass grafting (CABG) for more than 50 years. Endoscopic vein harvesting
      has greatly reduced the morbidity associated with obtaining the vein, but the
      quality of the vein could not be assessed before its was exposed surgically or
      after the endoscopic procedure had been performed. This study was conducted to
      evaluate the accuracy of preoperative mapping of the greater saphenous vein at
      the bedside in assessing suitable conduit size for use in CABG. METHODS: Seventy
      two consecutive patients undergoing saphenous vein harvesting for use as a
      conduit during CABG underwent preoperative ultrasonographic vein mapping on the
      operating table after the leg was positioned for vein harvesting. Vein diameters
      at 3 distinct locations were measured by ultrasonography after vein harvesting
      and preparation. Similar linear regression was used to determine the correlation
      between measurements by ultrasonography and the true vein size after harvesting.
      Standard methods of computing 95% lower and upper confidence limits for single
      predicted values were also used. RESULTS: Two hundred twenty measurements were
      obtained from 72 patients. Mean vein diameters were 3.4 +/- 0.9 and 4.6 +/- 0.9
      mm as measured by ultrasonography and after vein harvest, respectively. True vein
      size was an average of 1.2 +/- 0.4 mm larger than that measured by
      ultrasonography. Ultrasonographic determination of vein diameters closely
      correlated with the true vein diameter (correlation coefficient, 0.91; P < .001),
      and the measurement obtained predicted the true measurement within 1.6 mm with
      95% confidence. CONCLUSION: Bedside ultrasonographic vein mapping provides an
      accurate noninvasive method for preoperative assessment to determine the
      suitability of the greater saphenous vein for use as a bypass conduit. It is
      therefore an important component of preoperative planning before CABG.

PMID- 28439193
TI  - Hysteroscopic Management of Uterine Arteriovenous Malformation.
AB  - BACKGROUND AND OBJECTIVES: Uterine arteriovenous malformation (AVM) is
      characterized by shunts between the myometrial arteries and veins. Treatment is
      based on the severity of uterine bleeding and ranges from conservative medical
      approaches to embolization of affected arteries. The aim of study was to evaluate
      the feasibility and safety of hysteroscopy for management of uterine AVM.
      METHODS: This was a retrospective study of a cohort of 11 cases occurring between
      March 2012 and December 2015 in our Regional Center of Excellence in
      Hysteroscopy, University of Florence. The diagnosis of AVM was made by
      transvaginal ultrasonography with high-definition flow in patients with mild to
      moderate symptoms. In all cases, we used the hysteroscopic platform Gynecare
      VersaPoint II (Ethicon, Somerville, New Jersey, USA), equipped with a 4-mm
      electrosurgical loop and associated with the SPIES (Storz Professional Image
      Enhancement System) system (Karl Storz, Tuttlingen, Germany). RESULTS: All
      patients were successfully treated with operative hysteroscopy with no reported
      complications. No patient had residual disease detected by ultrasonography
      performed after a month. At this writing, of the 11 patients treated with
      operative hysteroscopy, 4 had achieved a pregnancy that carried to term, 1 was
      pregnant at 20 wk, and 1 had a miscarriage in the first trimester. CONCLUSIONS:
      Hysteroscopy is a feasible and safe alternative treatment modality for AVM.
      Patients treated with surgical hysteroscopy have high fertility outcomes, a 100%
      success rate after the first treatment, no complications related to the surgical
      procedure, and a short hospital stay.

PMID- 28439194
TI  - Fetal neonatal hyperthyroidism: diagnostic and therapeutic approachment.
AB  - Fetal and neonatal hyperthyroidism may occur in mothers with Graves' disease.
      Fetal thyrotoxicosis manifestation is observed with the transition of TSH
      receptor stimulating antibodies to the fetus from the 17th-20th weeks of
      pregnancy and with the fetal TSH receptors becoming responsive after 20 weeks.
      The diagnosis is confirmed by fetal tachycardia, goiter and bone age advancement
      in pregnancy and maternal treatment is conducted in accordance. The probability
      of neonatal hyperthyroidism is high in the babies of mothers that have ongoing
      antithyroid requirement and higher antibody levels in the last months of
      pregnancy. Clinical manifestation may be delayed by 7-17 days because of the
      antithyroid drugs taken by the mother. Neonatal hyperthyroidism symptoms can be
      confused with sepsis and congenital viral infections. Herein, the diagnosis and
      therapeutic approach are reviewed in cases of fetal neonatal hyperthyroidism.

PMID- 28439195
TI  - The role of serial measurements of serum insulin-like growth factor 1 levels in
      the development of retinopathy of prematurity.
AB  - AIM: To determine the role of serum insulin-like growth factor-1 levels in the
      development of retinopathy of prematurity, which is a major cause of childhood
      blindness worldwide. MATERIAL AND METHODS: We prospectively studied newborn
      infants born at a postmenstrual age of <32 weeks and birth weights <1 500 gr,
      between January 1st, 2015, and December 31st, 2015. A total of 40 infants were
      enrolled in the study. The retinal examination time was determined in accordance
      with the American Academy of Pediatrics recommendations for retinopathy of
      prematurity screening and follow-up. Retinopathy of prematurity was classified
      according to the international classification of retinopathy of prematurity.
      Serum Insulin like growth factor 1 levels were measured serially in blood samples
      on the 1st, 3rd, 7th, 21st, and 28th day. RESULTS: Among the 40 infants, 11
      (27.5%) constituted the retinopathy of prematurity group and 29 comprised the non
      retinopathy of prematurity group. In the retinopathy of prematurity group, the
      mean gestational age and birth weight was significantly lower. The demographic
      features of the study cohort were similar. The duration of mechanical ventilation
      was significantly greater in the retinopathy of prematurity group compared with
      the non-retinopathy of prematurity group (p=0.036). In terms of neonatal
      morbidities such as respiratory distress syndrome, intraventricular hemorrhage,
      bronchopulmonary dysplasia, patent ductus arteriosus, and necrotizing
      enterocolitis, no differences were detected between the groups. The mean serum
      insulin-like growth factor-1 levels in retinopathy of prematurity group were
      significantly lower than those in the non-retinopathy of prematurity group at
      each time point (1st, 3rd, 7th, 21st, and 28th day of postnatal life) (p=0.001).
      CONCLUSIONS: This study demonstrated the low serum insulin-like growth factor-1
      levels was associated with retinopathy of prematurity development.

PMID- 28439196
TI  - Clinical differences of influenza subspecies among hospitalized children.
AB  - AIM: Clinical findings, mortality, and morbidity rates differ among influenza
      subspecies. Awareness of these differences will lead physicians to choose the
      proper diagnostic and therapeutic strategies and to foresee possible
      complications. The aim of this study was to evaluate the clinical differences of
      influenza subspecies among hospitalized children. MATERIAL AND METHODS:
      Hospitalized children with proven influenza infection by polymerase chain
      reaction on nasopharyngeal swab specimens in our clinic, between December 2013
      and March 2016, were enrolled. These children were divided into 3 groups as
      Influenza A/H1N1 (n=42), Influenza A/H3N2 (n=23), and Influenza B (n=35).
      RESULTS: The median age of the children was 51.5 months (range, 3-204 months).
      The most common presenting symptoms were fever (n=83), cough (n=58), and
      difficulty in breathing (n=25). The most common non-respiratory findings were
      lymphadenopathy (n=18) and gastrointestinal system involvement (n=17). Sixty-two
      percent of the patients (n=62) had chronic diseases. H1N1 and H3N2 were
      significantly more common among patients with chronic neurologic disorders and
      renal failure, respectively. Leukopenia (n=32) and thrombocytopenia (n=22) were
      the most common pathologic laboratory findings. Neutropenia, elevated CRP levels,
      and antibiotic use were significantly more common among patients with H1N1
      infection. Seven patients were transferred to the intensive care unit with
      diagnoses of acute respiratory distress syndrome (n=4), encephalitis (n=2), and
      bronchiolitis (n=1). Two patients with chronic diseases and H1N1 infection died
      secondary to acute respiratory distress syndrome. CONCLUSIONS: Influenza A/H1N1
      infection represented more severe clinical disease.

PMID- 28439197
TI  - Clinical and polysomnographic features of children evaluated with polysomnography
      in pediatric sleep laboratory.
AB  - AIM: Sleep disordered breathing is a common problem in childhood that encompasses
      a spectrum of disorders extending from primary snoring to obstructive sleep
      apnea. This study aims to investigate the results of children undergoing
      evaluation with polysomnography in the sleep laboratory of a tertiary care
      hospital. MATERIAL AND METHODS: Demographic and clinical features as well as
      sleep associated symptoms, scores of pediatric sleep questionnaire and Pittsburgh
      sleep quality index and polysomnography results are retrospectively evaluated.
      RESULTS: Totally 131 patients were evaluated, of which 47.3% (n=62) were females
      and 52.7% (n=69) were males. Mean age was 101.85+/-59.15 months at the time of
      the study. Fifty percent (n=59) of patients complained of snoring and 43.7%
      (n=52) of patients complained of apnea during sleep. Mean obstructive hypopnea
      apnea index was 5.12+/-11.72. Mean obstructive hypopnea-apnea index of snorers
      (6.93+/-13.53) was significantly higher than the mean obstructive hypopnea-apnea
      index of nonsnorers (2.32+/-5.43) (p=0.011). Mean obstructive hypopnea-apnea
      index of patients experiencing apnea during sleep (7.52+/-14.25) was
      significantly higher than the mean obstructive hypopnea-apnea index of the
      children who do not experience apnea (2.61+/-5.84) (p=0.008). No significant
      correlation was observed between obstructive hypopnea-apnea index and scores of
      pediatric sleep questionnaire and Pittsburgh sleep quality index. The prevalence
      of obstructive sleep apnea was 33.6% (n=44). Forty nine patients (39.8%) were
      treated after polysomnography. Frequently suggested treatment options were
      noninvasive mechanical ventilation (n=23, 46.9%), intranasal steroid (n=15,
      30.6%), montelukast (n=11, 22.4%) and adenotonsillectomy (n=9, 18.4%).
      CONCLUSIONS: Polysomnography is the gold standard in the diagnosis of sleep
      disordered breathing in children. Pediatricians should be able to recognize early
      signs and symptoms of sleep disordered breathing and refer the patients in risk
      to centers where evaluation with polysomnography is available.

PMID- 28439198
TI  - Assessment of tumors in children with tuberous sclerosis: a single centre's
      experience.
AB  - AIM: As a result of mutations in TSC1 (9q34) and TSC2 (16p13.3) tumor supressor
      genes, the mammalian target of the rapamycin (mTor) signaling pathway is
      overactivated in patients with tuberous sclerosis. Abnormal cell proliferation
      and differentiation is responsible for the growth several different tumors. The
      aim of this study was to review tumors in our patients with tuberous sclerosis.
      MATERIAL AND METHODS: Thirty-six patients with tuberous sclerosis were reviewed
      retrospectively in terms of age, sex, family history, clinical findings, presence
      of tumors, and treatments. RESULTS: Our study included 36 patients (18/18:M/F)
      aged between two days and 17 years with a median age of 6 years. There were
      hypopigmented spots in 30 patients, seizures in 28 patients, and a family history
      in 11 patients. Tumors related to tuberous sclerosis were renal angiomyolipomas
      in 21 patients, cardiac rhabdomyomas in 11, subependymal giant cell astrocytomas
      in seven, and non renal hamartoma in one patient. Everolimus treatment was used
      in only two patients because of hemodynamic instability. CONCLUSIONS: Tuberous
      sclerosis is a multisystemic disease characterized by the presence of various
      benign tumors and neurologic disorders. Renal angiomyolipomas, cardiac
      rhabdomyomas, and subependymal giant cell astrocytomas are commonly observed in
      patients with tuberous sclerosis. mTOR inhibitors such as everolimus and
      sirolimus have been increasingly used in the treatment of these tumors. However,
      the duration and optimal dose of mTOR inhibitors is still controversial and
      should be used in selected cases.

PMID- 28439199
TI  - Comparison of methods and formulas used in umbilical venous catheter placement.
AB  - AIM: Central venous access is frequently provided by way of umbilical venous
      catheter placement in critically ill newborns. This study compared the methods of
      Dunn, Shukla-Ferrara, and Revised Shukla-Ferrara in determining the appropriate
      insertion length of umbilical vein catheters. MATERIAL AND METHODS: This
      prospective observational study was carried out in 121 newborns with umbilical
      venous catheter, group 1 (n=41) used Dunn method, group 2 (n=40) used the Shukla
      Ferrara formula, and group 3 used revised Shukla-Ferrara formula (n=40). Catheter
      tip position was evaluated with an anterior-posterior chest radiograph after
      insertion of the umbilical venous catheter. The ideal position for the umbilical
      venous catheter was defined as the catheter tip being visible between the 9th and
      10th thoracic vertebrae on an anterior-posterior chest radiograph. The position
      of the umbilical venous catheter was considered too high if the tip of the
      catheter was higher than the 9th thoracic vertebra and too low if the tip was
      below the 10th thoracic vertebra. The following data were collected: appropriate,
      inappropriate (low, high) placement, and complications of umbilical venous
      catheterization. RESULTS: In the Shukla-Ferrara group, 53% (17/32) of umbilical
      venous catheters were placed directly in the appropriate position, compared with
      40% (12/30) in the revised Shukla-Ferrara group and 38% (11/29) in the Dunn
      method group. Umbilical venous catheter-related complications developed in two
      patients, thrombus in one, and catheter-related blood stream infection in the
      other. CONCLUSIONS: This study showed that the Shukla-Ferrara formula is more
      accurate in predicting the insertion length for umbilical venous catheters,
      though statistical significance was not found. Further studies with larger
      samples are needed on this topic.

PMID- 28439200
TI  - Use of pericardium to repair anastomotic leak after esophageal atresia surgery;
      experience with one case.
AB  - Diverse therapies for the management of anastomotic leakage after esophageal
      atresia repair have been reported with various outcomes. The surgical management
      of anastomotic leakage after esophageal atresia repair can be challenging. We
      present a child with long-gap esophageal atresia and anastomotic leakage repair
      with pericardium. This article aimed to illustrate that pericardium may be a
      substitute for esophageal leakage repair.

PMID- 28439201
TI  - Diabulimia, a Type I diabetes mellitus-specific eating disorder.
AB  - Type I diabetes mellitus is the most common endocrinologic disorder affecting
      pediatric patients. Diet regimen adaptations in patients with diabetes may result
      in focusing on only diet and weight control, which causes eating disorders more
      often in these patients. Diabulimia is an eating disorder specific to patients
      with diabetes characterized by limiting and/or skipping insulin dosing. It is
      well observed that diet management and insulin treatment are withheld for body
      appearence and social acceptance issues, especially in patients whose disease is
      diagnosed during adolescence. We hereby present a patient who was diagnosed as
      having diabetes at the age of 12 years and skipped insulin doses in order to
      control weight and was subsequently diagnosed as having diabulimia.

PMID- 28439202
TI  - A rare complication of esophageal dilatation: Brain abscess.
AB  - Brain abscess is an uncommon serious disease, which has been reported as a rare
      complication of repeated esophageal dilations; however, routine periprocedural
      antibiotic prophylaxis is not currently recommended. Herein, we present a brain
      abscess that developed after esophageal dilatation for the treatment of induced
      caustic esophageal strictures. The clinical presentation is non-specific, the
      most reported signs are high fever and neurologic findings. Cases have been
      reported in the literature in adult and pediatric patients. Cranial imaging is
      essential for diagnosis, drainage and antibiotics are essential in its treatment.
      Clinical improvement was achieved with antibiotic therapy and surgical drainage.
      This serious complication should be kept in mind when treatment of corrosive
      strictures though repeated esophageal dilatation is planned and prophylaxis
      should be considered in selected patients.

PMID- 28439203
TI  - Cystic tuberculosis osteomyelitis of the distal tibia in infancy.
AB  - One-third of tuberculosis cases affect the musculoskeletal system. Solitary bone
      tuberculosis is a rare condition in infancy, has non-specific findings, and can
      be misdiagnosed easily. Cystic form tuberculosis may mimic many other pathologic
      conditions. In our case report, we present tuberculosis osteomyelitis of the
      distal tibia in a baby aged ten months who visited our outpatient department with
      swelling and pain in their left ankle. Curettage and debridement was performed
      twice for the lesion. An under-knee splint was applied for 3 months and anti
      tuberculosis treatment was given for 12 months. There was no relapse during a
      five-year follow-up period. There was no epiphysis injury and deformity. In this
      case report, we discuss that bone tuberculosis, as a rare condition, must be
      considered in lytic lesions of the distal tibia metaphysis in infancy.

PMID- 28439204
TI  - A revealing forehead cutaneuos lesion: Pott's "puffy" tumor.

PMID- 28439205
TI  - Two genera of Mymaridae (Hymenoptera) new to Africa, a remarkable new species of
      Anaphes and new generic synonymy.
AB  - Bakkendorfia Mathot, syn. n. is placed in synonymy under Cleruchus Enock and its
      only described species transferred as Cleruchus musangae (Mathot), comb.
      n.Anaphes quinquearticulatus Huber & Triapitsyn, sp. n. is described; it is the
      only known Anaphes Haliday species with a 5-segmented funicle in females. Two
      genera are reported for the first time from the Afrotropical region and two
      species are described: Paranaphoidea (Idiocentrus) africana Huber & Triapitsyn,
      sp. n., and Allanagrus occidentalis Huber & Triapitsyn, sp. n.

PMID- 28439206
TI  - Is OperaVOX a clinically useful tool for the assessment of voice in a general ENT
      clinic?
AB  - BACKGROUND: Objective acoustic analysis is a key component of multidimensional
      voice assessment. OperaVOX is an iOS app which has been shown to be comparable to
      Multi Dimensional Voice Program for most principal measures of vocal function. As
      a relatively cheap, portable and easily accessible form of acoustic analysis,
      OperaVOX may be more clinically useful than laboratory-based software in many
      situations. This study aims to determine whether correlation exists between
      acoustic measurements obtained using OperaVOX, and perceptual evaluation of
      voice. METHODS: Forty-four voices from the multidisciplinary voice clinic were
      examined. Each voice was assessed blindly by a single experienced voice therapist
      using the GRBAS scale, and analysed using OperaVOX. The Spearman rank correlation
      co-efficient was calculated between each element of the GRBAS scale and acoustic
      measurements obtained by OperaVOX. RESULTS: Significant correlations were
      identified between GRBAS scores and OperaVOX parameters. Grade correlated
      significantly with jitter (rho = 0.495, p < 0.05), shimmer (rho = 0.385, p <
      0.05), noise-to-harmonic ratio (NHR; rho = 0.526, p < 0.05) and maximum phonation
      time (MPT; rho = -0.415, p < 0.05). Roughness did not correlate with any of the
      measured variables. Breathiness correlated significantly with jitter (rho =
      0.342, p < 0.05), NHR (rho = 0.344, p < 0.05) and MPT (rho = -0.336, p < 0.05).
      Aesthenia correlated with NHR (rho = 0.413, p < 0.05) and MPT (rho = -0.399, p <
      0.05). Strain correlated with Jitter (rho = 0.560, p < 0.05), NHR (rho = 0.600, p
      < 0.05) and MPT (rho = -0.356, p < 0.05). CONCLUSIONS: OperaVOX provides
      objective acoustic analysis which has shown statistically significant correlation
      to perceptual evaluation using the GRBAS scale. The accessibility of the software
      package makes it possible for a wide range of health practitioners, e.g. general
      ENT surgeons, vascular surgeons, thyroid surgeons and cardiothoracic surgeons to
      objectively monitor outcomes and complications of surgical procedures that may
      affect vocal function. Given the increasing requirement for surgeons to monitor
      their outcomes as part of the move towards 'surgeon reported outcomes' this may
      become an invaluable tool towards that goal.

PMID- 28439207
TI  - Incidence and perception of nursing students' academic incivility in Oman.
AB  - BACKGROUND: The incidence of incivility in nursing education is increasing in
      most countries and it is affecting the culture of safety and the teaching
      learning processes. Despite reports of increasing trends, little is known about
      nursing students' academic incivility in the Middle East. This study aimed at
      exploring the perceptions and extent of academic incivility among nursing
      students (NS) and nursing faculty members (NF) in a university based
      undergraduate nursing program in Oman. METHODS: A quantitative cross sectional
      survey was used to explore NS academic incivility from the perspective of NS and
      NF in a public university in Oman. Data was obtained from a sample of 155 NS and
      40 NF using the Incivility in Nursing Education Survey. RESULTS: There was
      agreement between NS and NF on the majority of behaviors perceived to be
      disruptive. The incidence of NS academic incivility was moderate. The most common
      uncivil behaviors were acting bored or apathetic in class, holding conversations
      that distract others in class, using cell phones during class, arriving late for
      class, and being unprepared for class. There were significant differences between
      NF and NS perceived incidence of uncivil behaviors such as sleeping in class (p =
      0.016); not paying attention in class (p = 0.004); refusing to answer direct
      questions (p = 0.013); leaving class early (p = 0.000); cutting or not coming to
      class (p = 0.024); and creating tension by dominating class discussions (p =
      0.002). CONCLUSION: Student academic incivility is moderately present in nursing
      education in Oman, and this may have implications in terms of the future of the
      profession and patient care. There is need for more streamlined policies and
      strategies to curtail the incidence of academic incivility and to maintain safe
      and effective learning environments.

PMID- 28439209
TI  - Merging clinical chemistry biomarker data with a COPD database - building a
      clinical infrastructure for proteomic studies.
AB  - BACKGROUND: Data from biological samples and medical evaluations plays an
      essential part in clinical decision making. This data is equally important in
      clinical studies and it is critical to have an infrastructure that ensures that
      its quality is preserved throughout its entire lifetime. We are running a 5-year
      longitudinal clinical study, KOL-Orestad, with the objective to identify new COPD
      (Chronic Obstructive Pulmonary Disease) biomarkers in blood. In the study,
      clinical data and blood samples are collected from both private and public health
      care institutions and stored at our research center in databases and biobanks,
      respectively. The blood is analyzed by Mass Spectrometry and the results from
      this analysis then linked to the clinical data. METHOD: We built an
      infrastructure that allows us to efficiently collect and analyze the data. We
      chose to use REDCap as the EDC (Electronic Data Capture) tool for the study due
      to its short setup-time, ease of use, and flexibility. REDCap allows users to
      easily design data collection modules based on existing templates. In addition,
      it provides two functions that allow users to import batches of data; through a
      web API (Application Programming Interface) as well as by uploading CSV-files
      (Comma Separated Values). RESULTS: We created a software, DART (Data Rapid
      Translation), that translates our biomarker data into a format that fits REDCap's
      CSV-templates. In addition, DART is configurable to work with many other data
      formats as well. We use DART to import our clinical chemistry data to the REDCap
      database. CONCLUSION: We have shown that a powerful and internationally adopted
      EDC tool such as REDCap can be extended so that it can be used efficiently in
      proteomic studies. In our study, we accomplish this by using DART to translate
      our clinical chemistry data to a format that fits the templates of REDCap.

PMID- 28439210
TI  - Violence in context: Embracing an ecological approach to violent media exposure.
AB  - This commentary expands on Anderson, Bushman, Donnerstein, Hummer, and
      Warburton's agenda for minimizing the impacts of violent media exposure (VME) on
      youth aggression. We argue that in order to effectively intervene in the
      development of aggression and other maladaptive traits, researchers and
      policymakers should take an ecological, developmental psychopathology approach to
      understanding children's exposure to VME within developmental, relational,
      environmental, and cultural contexts. Such a framework holds the most promise for
      identifying at-risk groups, establishing targets of intervention, and testing
      mechanisms of change.

PMID- 28439208
TI  - Proteomic profiling of HBV infected liver biopsies with different fibrotic
      stages.
AB  - BACKGROUND: Hepatitis B virus (HBV) is a global health problem, and infected
      patients if left untreated may develop cirrhosis and eventually hepatocellular
      carcinoma. This study aims to enlighten pathways associated with HBV related
      liver fibrosis for delineation of potential new therapeutic targets and
      biomarkers. METHODS: Tissue samples from 47 HBV infected patients with different
      fibrotic stages (F1 to F6) were enrolled for 2D-DIGE proteomic screening.
      Differentially expressed proteins were identified by mass spectrometry and
      verified by western blotting. Functional proteomic associations were analyzed by
      EnrichNet application. RESULTS: Fibrotic stage variations were observed for
      apolipoprotein A1 (APOA1), pyruvate kinase PKM (KPYM), glyceraldehyde 3
      phospahate dehydrogenase (GAPDH), glutamate dehydrogenase (DHE3), aldehyde
      dehydrogenase (ALDH2), alcohol dehydrogenase (ALDH1A1), transferrin (TRFE),
      peroxiredoxin 3 (PRDX3), phenazine biosynthesis-like domain-containing protein
      (PBLD), immuglobulin kappa chain C region (IGKC), annexin A4 (ANXA4), keratin 5
      (KRT5). Enrichment analysis with Reactome and Kegg databases highlighted the
      possible involvement of platelet release, glycolysis and HDL mediated lipid
      transport pathways. Moreover, string analysis revealed that HIF-1alpha (Hypoxia
      inducible factor 1-alpha), one of the interacting partners of HBx (Hepatitis B X
      protein), may play a role in the altered glycolytic response and oxidative stress
      observed in liver fibrosis. CONCLUSIONS: To our knowledge, this is the first
      protomic research that studies HBV infected fibrotic human liver tissues to
      investigate alterations in protein levels and affected pathways among different
      fibrotic stages. Observed changes in the glycolytic pathway caused by HBx
      presence and therefore its interactions with HIF-1alpha can be a target pathway
      for novel therapeutic purposes.

PMID- 28439211
TI  - Examining the relations between self-regulation and achievement in third grade
      students.
AB  - Children with stronger self-regulation skills generally demonstrate greater
      overall success in school both academically and socially. However, there are few
      valid and reliable measures of self-regulation in middle elementary school. Such
      a measure could help identify whether a child is truly having difficulties. Thus,
      the Remembering Rules and Regulation Picture Task (RRRP) was developed. The aim
      of this study was to develop scoring systems for the RRRP and then to examine the
      associations between RRRP and independent measures of self-regulation and
      academic achievement in mathematics and reading. Children (n = 282) from 34 third
      grade classrooms in Florida participated in this study. Results revealed that the
      RRRP captured three constructs: working memory, attentional flexibility, and
      inhibitory control. Hierarchical linear modeling (HLM) demonstrated that the RRRP
      was significantly and positively associated with other measures of self
      regulation. The RRRP was significantly and positively associated with mathematics
      and reading as well. The RRRP appears to be a promising measure of children's
      self-regulation skills.

PMID- 28439214
TI  - Foreword of the Editor.

PMID- 28439212
TI  - Effect of thyme extract supplementation on lipid peroxidation, antioxidant
      capacity, PGC-1alpha content and endurance exercise performance in rats.
AB  - BACKGROUND: Athletes have a large extent of oxidant agent production. In the
      current study, we aimed to determine the influence of thyme extract on the
      endurance exercise performance, mitochondrial biogenesis, and antioxidant status
      in rats. METHODS: Twenty male Wistar rats were randomly divided into two groups
      receiving either normal drinking water (non-supplemented group, n = 10) or thyme
      extract, 400 mg/kg, (supplemented group, n = 10). Rats in both groups were
      subjected to endurance treadmill training (27 m/min, 10% grade, 60 min, and 5
      days/week for 8 weeks). Finally, to determine the endurance capacity, time to
      exhaustion treadmill running at 36 m/min speed was assessed. At the end of the
      endurance capacity test, serum and soleus muscle samples were collected and their
      superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as well as
      malondialdehyde (MDA) concentration were measured. Protein expression of PGC
      1alpha, as a marker of mitochondrial biogenesis, was also determined in the
      soleus muscle tissue by immunoblotting assay. RESULTS: Findings revealed that the
      exhaustive running time in the treatment group was significantly (p < 0.05)
      prolonged. Both serum and soleus muscle MDA levels, as an index of lipid
      peroxidation, had a threefold increase in the thyme extract supplemented group
      (t18 = 8.11, p < 0.01; t18 = 4.98, p < 0.01 respectively). The activities of SOD
      and GPx of the soleus muscle were significantly (p < 0.05) higher in the non
      supplemented group, while there was no significant difference in serum SOD, GPx
      activities, and total antioxidant capacity between groups. Furthermore, thyme
      supplementation significantly (p < 0.05) decreased PGC-1alpha expression.
      CONCLUSIONS: Thyme extract supplementation increased endurance exercise tolerance
      in intact animals, although decrease of oxidative stress and regulation of the
      PGC-1alpha protein expression are not considered as underlying molecular
      mechanisms.

PMID- 28439213
TI  - A clinical perspective on the utility of alpha 1 antichymotrypsin for the early
      diagnosis of calcific aortic stenosis.
AB  - BACKGROUND: Calcific aortic stenosis (CAS) is the most common heart valve disease
      in the elderly, representing an important economic and social burden in developed
      countries. Currently, there is no way to predict either the onset or progression
      of CAS, emphasizing the need to identify useful biomarkers for this condition.
      METHODS: We performed a multi-proteomic analysis on different kinds of samples
      from CAS patients and healthy donors: tissue, secretome and plasma. The results
      were validated in an independent cohort of subjects by immunohistochemistry,
      western blotting and selected reaction monitoring. RESULTS: Alpha 1
      antichymotrypsin (AACT) abundance was altered in the CAS samples, as confirmed in
      the validation phase. The significant changes observed in the amounts of this
      protein strongly suggest that it could be involved in the molecular mechanisms
      underlying CAS. In addition, our results suggest there is enhanced release of
      AACT into the extracellular fluids when the disease commences. CONCLUSIONS: The
      significant increase of AACT in CAS patients suggests it fulfils an important
      role in the physiopathology of this disease. These results permit us to propose
      that AACT may serve as a potential marker for the diagnosis of CAS, with
      considerable clinical value.

PMID- 28439215
TI  - Recent Advances in Pediatric Laboratory Medicine.

PMID- 28439216
TI  - Pediatric Obesity and Cardiometabolic Disorders: Risk Factors and Biomarkers.
AB  - Obesity remains the most prevailing disorder in childhood males and females
      worldwide. Its high prevalence markedly predisposes children to insulin
      resistance, hypertension, hyperlipidemia and liver disorders while enhancing the
      risk of type 2 diabetes and cardiovascular diseases. In this review, the
      relationship of obesity with genetic and environmental factors will be described
      and the underlined causes will briefly be reported. As obesity in children
      constitutes an increasingly health concern, important potential biomarkers have
      been discussed for the diagnosis, treatment and follow-up of the wide range of
      overweight-related complications. Awareness about the applicability and
      limitations of these preventive and predictive biomarkers will intensify the
      research and medical efforts for new developments in order to efficiently
      struggle against childhood obesity.

PMID- 28439217
TI  - Pediatric Metabolic Syndrome: Pathophysiology and Laboratory Assessment.
AB  - Pediatric overweight and obesity is an emerging public health priority as rates
      have rapidly increased worldwide. Obesity is often clustered with other metabolic
      abnormalities including hypertension, dyslipidemia, and insulin resistance,
      leading to increased risk of cardiovascular disease. This cluster of risk
      factors, termed the metabolic syndrome, has traditionally been reported in
      adults. However, with the increased prevalence of pediatric obesity, the
      metabolic syndrome is now evident in children and adolescents. This complex
      cluster of risk factors is the result of the pathological interplay between
      several organs including adipose tissue, muscle, liver, and intestine with a
      common antecedent - insulin resistance. The association of the metabolic syndrome
      with several systemic alterations that involve numerous organs and tissues adds
      to the complexity and challenge of diagnosing the metabolic syndrome and
      identifying useful clinical indicators of the disease. The complex physiology of
      growing and developing children and adolescents further adds to the difficulties
      in standardizing laboratory assessment, diagnosis, and prognosis for the diverse
      pediatric population. However, establishing a consensus definition is critical to
      identifying and managing children and adolescents at high risk of developing the
      metabolic syndrome. As a result, the examination of novel metabolic syndrome
      biomarkers which can detect these metabolic abnormalities early with high
      specificity and sensitivity in the pediatric population has been of interest.
      Understanding this complex cluster of risk factors in the pediatric population is
      critical to ensure that this is not the first generation where children have a
      shorter life expectancy than their parents. This review will discuss the
      pathophysiology, consensus definitions and laboratory assessment of pediatric
      metabolic syndrome as well as potential novel biomarkers.

PMID- 28439218
TI  - Pediatric Reference Intervals for Biochemical Markers: Gaps and Challenges,
      Recent National Initiatives and Future Perspectives.
AB  - Reference intervals provide valuable information to medical practitioners in
      their interpretation of quantitative laboratory test results, and are critical in
      the assessment of patient health and in clinical decision-making. The reference
      interval serves as a health-associated benchmark with which to compare an
      individual test result. While the concept of reference intervals and their
      utility appear straightforward, the process of establishing accurate and reliable
      reference intervals is considerably complex and involved. Currently, many
      pediatric laboratory tests are inappropriately interpreted using reference
      intervals derived from either adult populations, hospitalized pediatric
      populations, or from outdated and/or inaccurate technology. Thus, many pediatric
      reference intervals used in diagnostic laboratories are incomplete and may be
      inappropriate for clinical use. The use of inappropriate reference intervals
      impacts clinical decision-making and has potential detrimental effects on the
      quality of patient healthcare including misdiagnosis, delayed diagnosis,
      inappropriate treatments, and patient risk. These are critical gaps in pediatric
      healthcare and it is imperative to update and establish appropriate reference
      intervals for pediatric populations based on specific age- and sex
      stratifications. In the present review, specific issues, challenges and
      deficiencies in pediatric reference intervals for biochemical markers will be
      discussed. Early studies using hospitalized patients will be examined, followed
      by a review of recent national and global initiatives on establishing reference
      intervals from healthy pediatric population. We will highlight the achievements
      and milestones of the Canadian CALIPER project, including the establishment of a
      comprehensive biobank and database which has addressed several of these critical
      gaps. CALIPER's mandate is to establish and provide comprehensive, up-to-date
      pediatric reference intervals to all biochemical markers of pediatric disease.
      CALIPER has also begun knowledge translation initiatives to disseminate its data
      via peer-reviewed publication, an online database, and a smartphone application
      to allow greater access to CALIPER pediatric reference interval data. Finally,
      limitations, future perspectives and harmonization of pediatric reference
      intervals to improve pediatric diagnostics in Canada and worldwide will be
      discussed.

PMID- 28439219
TI  - The Utility of CSF for the Diagnosis of Primary and Secondary Monoamine
      Neurotransmitter Deficiencies.
AB  - Biogenic amine defects constitute a complex and expanding group of
      neurotransmitter disorders affecting cognitive, motor and autonomic system
      development, mostly in the pediatric age. In recent years different enzymatic
      defects have been identified impairing the tetrahydrobiopterin cofactor pathway
      and/or biogenic amine synthesis, catabolism and transport, with subsequent new
      disease entities described. The lumbar puncture, with subsequent withdrawal of
      cerebrospinal fluid (CSF), remains a key step in the diagnostic procedure. Due to
      the specific nature of CSF, timing of analysis, sample collection and storage,
      technical issues of the analytic process are still crucial for the diagnosis and
      follow-up of patients. A progressive approach to the diagnosis of biogenic amine
      defects is presented, pointing out criticalities and difficulties concerning
      sample collection and results interpretation, especially due to the increasing
      reports of secondary neurotransmitter alterations that, at present, constitute a
      challenge.

PMID- 28439220
TI  - Pediatric Reference Intervals for Transferrin Saturation in the CALIPER Cohort of
      Healthy Children and Adolescents.
AB  - BACKGROUND: Transferrin saturation reference intervals specific for age and sex
      have not been previously reported for the pediatric population. The reference
      values for transferrin saturation have been previously reported to be lower in
      children compared to adults, caused by a combination of low serum iron and high
      serum transferrin levels in children, warranting specific reference intervals.
      Here we use the original iron and transferrin data from the CALIPER cohort to
      establish age- and sex-specific pediatric reference intervals for transferrin
      saturation. METHODS: Iron and transferrin concentrations were measured in serum
      samples from the CALIPER cohort of healthy children and adolescents on the Abbott
      Architect c8000. Transferrin saturation was subsequently calculated and
      statistically relevant age- and sex-partitions were determined. After removing
      outliers, age- and sex-specific reference intervals with corresponding 90%
      confidence intervals were calculated using CLSI C28-A3 guidelines. RESULTS:
      Transferrin saturation required 3 separate age partitions, with an additional sex
      partition for 14-<19 year olds. Transferrin saturation was more variable during
      the first year of life, evident by a wider reference interval, which subsequently
      narrowed at one year until adolescence. Upon adolescence, a sex difference was
      apparent with females having lower percent transferrin saturation than males.
      CONCLUSIONS: Age- and sex-specific pediatric reference intervals for transferrin
      saturation were established based on a large cohort of healthy pediatric
      subjects. Transference studies suggest that these intervals established using
      Abbott assays are comparable to those on Beckman, Ortho, Roche, and Siemens
      assays. Individual laboratories should however verify these reference intervals
      for their individual instrument and local population as per CLSI guidelines.

PMID- 28439221
TI  - Congenital Hyperinsulinism Caused by a De Novo Mutation in the ABCC8 Gene - A
      Case Report.
AB  - Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by
      inappropriate insulin secretion and severe hypoglycaemia. There are two
      histological subtypes: diffuse and focal form. Diffuse form is most common in
      autosomal recessive mutations in ABCC8/KCNJ11 gene, while focal CHI is caused a
      paternally inherited mutation and a somatic maternal allele loss. Here we report
      a case of a term male infant presented with severe hyperinsulinaemic
      hypoglycaemia. Gene panel testing was performed to give rapid genetic diagnosis.
      We detected the c.4415-13G>A heterozygous mutation in the ABCC8 gene. Targeted
      genetic testing of the parents proved the de novo origin of the mutation. The
      mutation has been previously described. The infant received octreotide treatment
      and is prepared for 18-fluoro-dopa PET-CT examination in order to localize the
      lesion. Rapid genetic testing might be crucial in the clinical management
      strategy, with decision algorithms taking into account of the genetic status of
      the patient.

PMID- 28439222
TI  - Hemochromatosis, Erythrocytosis and the JAK2 p.V617F Mutation.

PMID- 28439223
TI  - Outer Hair Cell and Auditory Nerve Function in Speech Recognition in Quiet and in
      Background Noise.
AB  - The goal of this study was to describe the contribution of outer hair cells
      (OHCs) and the auditory nerve (AN) to speech understanding in quiet and in the
      presence of background noise. Fifty-three human subjects with hearing ranging
      from normal to moderate sensorineural hearing loss were assayed for both speech
      in quiet (Word Recognition) and speech in noise (QuickSIN test) performance.
      Their scores were correlated with OHC function as assessed via distortion product
      otoacoustic emissions, and AN function as measured by amplitude, latency, and
      threshold of the VIIIth cranial nerve Compound Action Potential (CAP) recorded
      during electrocochleography (ECochG). Speech and ECochG stimuli were presented at
      equivalent sensation levels in order to control for the degree of hearing
      sensitivity across patients. The results indicated that (1) OHC dysfunction was
      evident in the lower range of normal audiometric thresholds, which demonstrates
      that OHC damage can produce "Hidden Hearing Loss," (2) AN dysfunction was evident
      beginning at mild levels of hearing loss, (3) when controlled for normal OHC
      function, persons exhibiting either high or low ECochG amplitudes exhibited no
      statistically significant differences in neither speech in quiet nor speech in
      noise performance, (4) speech in noise performance was correlated with OHC
      function, (5) hearing impaired subjects with OHC dysfunction exhibited better
      speech in quiet performance at or near threshold when stimuli were presented at
      equivalent sensation levels. These results show that OHC dysfunction contributes
      to hidden hearing loss, OHC function is required for optimum speech in noise
      performance, and those persons with sensorineural hearing loss exhibit better
      word discrimination in quiet at or near their audiometric thresholds than normal
      listeners.

PMID- 28439224
TI  - Richness in Functional Connectivity Depends on the Neuronal Integrity within the
      Posterior Cingulate Cortex.
AB  - The brain's connectivity skeleton-a rich club of strongly interconnected members
      was initially shown to exist in human structural networks, but recent evidence
      suggests a functional counterpart. This rich club typically includes key regions
      (or hubs) from multiple canonical networks, reducing the cost of inter-network
      communication. The posterior cingulate cortex (PCC), a hub node embedded within
      the default mode network, is known to facilitate communication between brain
      networks and is a key member of the "rich club." Here, we assessed how metabolic
      signatures of neuronal integrity and cortical thickness influence the global
      extent of a functional rich club as measured using the functional rich club
      coefficient (fRCC). Rich club estimation was performed on functional connectivity
      of resting state brain signals acquired at 3T in 48 healthy adult subjects.
      Magnetic resonance spectroscopy was measured in the same session using a point
      resolved spectroscopy sequence. We confirmed convergence of functional rich club
      with a previously established structural rich club. N-acetyl aspartate (NAA) in
      the PCC is significantly correlated with age (p = 0.001), while the rich club
      coefficient showed no effect of age (p = 0.106). In addition, we found a
      significant quadratic relationship between fRCC and NAA concentration in PCC (p =
      0.009). Furthermore, cortical thinning in the PCC was correlated with a reduced
      rich club coefficient after accounting for age and NAA. In conclusion, we found
      that the fRCC is related to a marker of neuronal integrity in a key region of the
      cingulate cortex. Furthermore, cortical thinning in the same area was observed,
      suggesting that both cortical thinning and neuronal integrity in the hub regions
      influence functional integration of at a whole brain level.

PMID- 28439225
TI  - Magnitude Codes for Cross-Modal Working Memory in the Primate Frontal Association
      Cortex.
AB  - Quantitative features of stimuli may be ordered along a magnitude continuum, or
      line. Magnitude refers to parameters of different types of stimulus properties.
      For instance, the frequency of a sound relates to sensory and continuous stimulus
      properties, whereas the number of items in a set is an abstract and discrete
      property. In addition, within a stimulus property, magnitudes need to be
      processed not only in one modality, but across multiple modalities. In the
      sensory domain, for example, magnitude applies to both to the frequency of
      auditory sounds and tactile vibrations. Similarly, both the number of visual
      items and acoustic events constitute numerical quantity, or numerosity. To
      support goal-directed behavior and executive functions across time, magnitudes
      need to be held in working memory, the ability to briefly retain and manipulate
      information in mind. How different types of magnitudes across multiple modalities
      are represented in working memory by single neurons has only recently been
      explored in primates. These studies show that neurons in the frontal lobe can
      encode the same magnitude type across sensory modalities. However, while
      multimodal sensory magnitude in relative comparison tasks is represented by
      monotonically increasing or decreasing response functions ("summation code"),
      multimodal numerical quantity in absolute matching tasks is encoded by neurons
      tuned to preferred numerosities ("labeled-line code"). These findings indicate
      that most likely there is not a single type of cross-modal working-memory code
      for magnitudes, but rather a flexible code that depends on the stimulus dimension
      as well as on the task requirements.

PMID- 28439226
TI  - The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability
      and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post
      synaptic Densities.
AB  - Phosphodiesterase regulates the homeostasis of cAMP and cGMP, which increase the
      strength of excitatory neural circuits and/or decrease inhibitory synaptic
      plasticity. Abnormally, synchronized synaptic transmission in the brain leads to
      seizures. A phosphodiesterase 10A (PDE10A) inhibitor PF-2545920 has recently
      attracted attention as a potential therapy for neurological and psychiatric
      disorders. We hypothesized that PF-2545920 plays an important role in status
      epilepticus (SE) and investigated the underlying mechanisms. PDE10A was primarily
      located in neurons, and PDE10A expression increased significantly in patients
      with temporal lobe epilepsy. PF-2545920 enhanced the hyperexcitability of
      pyramidal neurons in rat CA1, as measured by the frequency of action potentials
      and miniature excitatory post-synaptic current. GluA1 and NR2A expression also
      increased significantly in post-synaptic densities, with or without SE in rats
      treated with PF-2545920. The ratio of p-GluA1/GluA1 increased in the presence of
      PF-2545920 in groups with SE. Our results suggest that PF-2545920 facilitates
      seizure activity via the intracellular redistribution of GluA1 and NR2A in the
      hippocampus. The upregulation of p-GluA1 may play an important role in
      trafficking GluA1 to post-synaptic densities. The data suggest it would be
      detrimental to use the drug in seizure patients and might cause neuronal
      hyperexcitability in non-epileptic individuals.

PMID- 28439227
TI  - Requirement of NF-kappa B Activation in Different Mice Brain Areas during Long
      Term Memory Consolidation in Two Contextual One-Trial Tasks with Opposing
      Valences.
AB  - NF-kappa B is a transcription factor whose activation has been shown to be
      necessary for long-term memory consolidation in several species. NF-kappa B is
      activated and translocates to the nucleus of cells in a specific temporal window
      during consolidation. Our work focuses on a one trial learning tasks associated
      to the inhibitory avoidance (IA) setting. Mice were trained either receiving or
      not a footshock when entering a dark compartment (aversive vs. appetitive
      learning). Regardless of training condition (appetitive or aversive), latencies
      to step-through during testing were significantly different to those measured
      during training. Additionally, these testing latencies were also different from
      those of a control group that only received a shock unrelated to context.
      Moreover, nuclear NF-kappa B DNA-binding activity was augmented in the aversive
      and the appetitive tasks when compared with control and naive animals. NF-kappa B
      inhibition by Sulfasalazine injected either in the Hippocampus, Amygdala or
      Nucleus accumbens immediately after training was able to impair retention in both
      training versions. Our results suggest that NF-kappa B is a critical molecular
      step, in different brain areas on memory consolidation. This was the case for
      both the IA task and also the modified version of the same task where the
      footshock was omitted during training. This work aims to further investigate how
      appetitive and aversive memories are consolidated.

PMID- 28439229
TI  - Locomotion-Related Population Cortical Ca2+ Transients in Freely Behaving Mice.
AB  - Locomotion involves complex neural activity throughout different cortical and
      subcortical networks. The primary motor cortex (M1) receives a variety of
      projections from different brain regions and is responsible for executing
      movements. The primary visual cortex (V1) receives external visual stimuli and
      plays an important role in guiding locomotion. Understanding how exactly the M1
      and the V1 are involved in locomotion requires recording the neural activities in
      these areas in freely moving animals. Here, we used an optical fiber-based method
      for the real-time monitoring of neuronal population activities in freely moving
      mice. We combined the bulk loading of a synthetic Ca2+ indicator and the optical
      fiber-based Ca2+ recordings of neuronal activities. An optical fiber 200 MUm in
      diameter can detect the coherent activity of a subpopulation of neurons. In layer
      5 of the M1 and V1, we showed that population Ca2+ transients reliably occurred
      preceding the impending locomotion. Interestingly, the M1 Ca2+ transients started
      ~100 ms earlier than that in V1. Furthermore, the population Ca2+ transients were
      robustly correlated with head movements. Thus, our work provides a simple but
      efficient approach for monitoring the cortical Ca2+ activity of a local cluster
      of neurons during locomotion in freely moving animals.

PMID- 28439230
TI  - From Anxious to Reckless: A Control Systems Approach Unifies Prefrontal-Limbic
      Regulation Across the Spectrum of Threat Detection.
AB  - Here we provide an integrative review of basic control circuits, and introduce
      techniques by which their regulation can be quantitatively measured using human
      neuroimaging. We illustrate the utility of the control systems approach using
      four human neuroimaging threat detection studies (N = 226), to which we applied
      circuit-wide analyses in order to identify the key mechanism underlying
      individual variation. In so doing, we build upon the canonical prefrontal-limbic
      control system to integrate circuit-wide influence from the inferior frontal
      gyrus (IFG). These were incorporated into a computational control systems model
      constrained by neuroanatomy and designed to replicate our experimental data. In
      this model, the IFG acts as an informational set point, gating signals between
      the primary prefrontal-limbic negative feedback loop and its cortical information
      gathering loop. Along the cortical route, if the sensory cortex provides
      sufficient information to make a threat assessment, the signal passes to the
      ventromedial prefrontal cortex (vmPFC), whose threat-detection threshold
      subsequently modulates amygdala outputs. However, if signal outputs from the
      sensory cortex do not provide sufficient information during the first pass, the
      signal loops back to the sensory cortex, with each cycle providing increasingly
      fine-grained processing of sensory data. Simulations replicate IFG (chaotic)
      dynamics experimentally observed at both ends at the threat-detection spectrum.
      As such, they identify distinct types of IFG disconnection from the circuit, with
      associated clinical outcomes. If IFG thresholds are too high, the IFG and sensory
      cortex cycle for too long; in the meantime the coarse-grained (excitatory)
      pathway will dominate, biasing ambiguous stimuli as false positives. On the other
      hand, if cortical IFG thresholds are too low, the inhibitory pathway will
      suppress the amygdala without cycling back to the sensory cortex for much-needed
      fine-grained sensory cortical data, biasing ambiguous stimuli as false negatives.
      Thus, the control systems model provides a consistent mechanism for IFG
      regulation, capable of producing results consistent with our data for the full
      spectrum of threat-detection: from fearful to optimal to reckless. More
      generally, it illustrates how quantitative characterization of circuit dynamics
      can be used to unify a fundamental dimension across psychiatric affective
      symptoms, with implications for populations that range from anxiety disorders to
      addiction.

PMID- 28439228
TI  - From Engrams to Pathologies of the Brain.
AB  - Memories are the experiential threads that tie our past to the present. The
      biological realization of a memory is termed an engram-the enduring biochemical
      and physiological processes that enable learning and retrieval. The past decade
      has witnessed an explosion of engram research that suggests we are closing in on
      boundary conditions for what qualifies as the physical manifestation of memory.
      In this review, we provide a brief history of engram research, followed by an
      overview of the many rodent models available to probe memory with intersectional
      strategies that have yielded unprecedented spatial and temporal resolution over
      defined sets of cells. We then discuss the limitations and controversies
      surrounding engram research and subsequently attempt to reconcile many of these
      views both with data and by proposing a conceptual shift in the strategies
      utilized to study memory. We finally bridge this literature with human memory
      research and disorders of the brain and end by providing an experimental
      blueprint for future engram studies in mammals. Collectively, we believe that we
      are in an era of neuroscience where engram research has transitioned from
      ephemeral and philosophical concepts to provisional, tractable, experimental
      frameworks for studying the cellular, circuit and behavioral manifestations of
      memory.

PMID- 28439231
TI  - Informing the Structure of Executive Function in Children: A Meta-Analysis of
      Functional Neuroimaging Data.
AB  - The structure of executive function (EF) has been the focus of much debate for
      decades. What is more, the complexity and diversity provided by the developmental
      period only adds to this contention. The development of executive function plays
      an integral part in the expression of children's behavioral, cognitive, social,
      and emotional capabilities. Understanding how these processes are constructed
      during development allows for effective measurement of EF in this population.
      This meta-analysis aims to contribute to a better understanding of the structure
      of executive function in children. A coordinate-based meta-analysis was conducted
      (using BrainMap GingerALE 2.3), which incorporated studies administering
      functional magnetic resonance imaging (fMRI) during inhibition, switching, and
      working memory updating tasks in typical children (aged 6-18 years). The neural
      activation common across all executive tasks was compared to that shared by tasks
      pertaining only to inhibition, switching or updating, which are commonly
      considered to be fundamental executive processes. Results support the existence
      of partially separable but partially overlapping inhibition, switching, and
      updating executive processes at a neural level, in children over 6 years.
      Further, the shared neural activation across all tasks (associated with a
      proposed "unitary" component of executive function) overlapped to different
      degrees with the activation associated with each individual executive process.
      These findings provide evidence to support the suggestion that one of the most
      influential structural models of executive functioning in adults can also be
      applied to children of this age. However, the findings also call for careful
      consideration and measurement of both specific executive processes, and unitary
      executive function in this population. Furthermore, a need is highlighted for a
      new systematic developmental model, which captures the integrative nature of
      executive function in children.

PMID- 28439232
TI  - Mapping the Speech Code: Cortical Responses Linking the Perception and Production
      of Vowels.
AB  - The acoustic realization of speech is constrained by the physical mechanisms by
      which it is produced. Yet for speech perception, the degree to which listeners
      utilize experience derived from speech production has long been debated. In the
      present study, we examined how sensorimotor adaptation during production may
      affect perception, and how this relationship may be reflected in early vs. late
      electrophysiological responses. Participants first performed a baseline speech
      production task, followed by a vowel categorization task during which EEG
      responses were recorded. In a subsequent speech production task, half the
      participants received shifted auditory feedback, leading most to alter their
      articulations. This was followed by a second, post-training vowel categorization
      task. We compared changes in vowel production to both behavioral and
      electrophysiological changes in vowel perception. No differences in phonetic
      categorization were observed between groups receiving altered or unaltered
      feedback. However, exploratory analyses revealed correlations between vocal motor
      behavior and phonetic categorization. EEG analyses revealed correlations between
      vocal motor behavior and cortical responses in both early and late time windows.
      These results suggest that participants' recent production behavior influenced
      subsequent vowel perception. We suggest that the change in perception can be best
      characterized as a mapping of acoustics onto articulation.

PMID- 28439233
TI  - Concealed, Unobtrusive Ear-Centered EEG Acquisition: cEEGrids for Transparent
      EEG.
AB  - Electroencephalography (EEG) is an important clinical tool and frequently used to
      study the brain-behavior relationship in humans noninvasively. Traditionally, EEG
      signals are recorded by positioning electrodes on the scalp and keeping them in
      place with glue, rubber bands, or elastic caps. This setup provides good coverage
      of the head, but is impractical for EEG acquisition in natural daily-life
      situations. Here, we propose the transparent EEG concept. Transparent EEG aims
      for motion tolerant, highly portable, unobtrusive, and near invisible data
      acquisition with minimum disturbance of a user's daily activities. In recent
      years several ear-centered EEG solutions that are compatible with the transparent
      EEG concept have been presented. We discuss work showing that miniature
      electrodes placed in and around the human ear are a feasible solution, as they
      are sensitive enough to pick up electrical signals stemming from various brain
      and non-brain sources. We also describe the cEEGrid flex-printed sensor array,
      which enables unobtrusive multi-channel EEG acquisition from around the ear. In a
      number of validation studies we found that the cEEGrid enables the recording of
      meaningful continuous EEG, event-related potentials and neural oscillations.
      Here, we explain the rationale underlying the cEEGrid ear-EEG solution, present
      possible use cases and identify open issues that need to be solved on the way
      toward transparent EEG.

PMID- 28439234
TI  - Salivary Oxytocin Concentration Associates with the Subjective Feeling of Body
      Ownership during the Rubber Hand Illusion.
AB  - Oxytocin is a hormone of the posterior pituitary that promotes lactation,
      maternal bonding, and birth. Recent studies have shown that oxytocin may modulate
      social recognition in both sexes, and thus it may be related to empathy. Brain
      regions that are associated with social recognition and empathy (e.g., the
      insular cortex) are activated in the rubber hand illusion (RHI), which involves
      illusory ownership of a rubber hand caused by brush strokes applied synchronously
      to both a rubber hand and one of the participant's hand, which is hidden from
      view. It is intriguing to examine whether oxytocin modulates plastic changes in
      body representation, such as the changes occurring in the RHI. In the present
      study, we investigated the relationship between salivary oxytocin concentration
      and the feeling of rubber hand ownership. Brush strokes were applied
      synchronously or asynchronously to the participant's hand and a rubber hand on
      different days. Salivary oxytocin was measured before and after the behavioral
      tasks. We found that participants who had high concentrations of salivary
      oxytocin tended to feel strong ownership of the rubber hand. We also found that
      the participants with a high autism spectrum quotient (AQ) score who particularly
      felt difficulties in social skills and communications tended to feel weak rubber
      hand ownership. We observed that illusory body ownership was closely linked to
      social communications and a related neuroendocrine basis. The results of the
      present study suggest that an individual's salivary oxytocin concentration can
      predict the extent to which the individual experiences the RHI; furthermore,
      oxytocin might modulate the sensation of body ownership.

PMID- 28439235
TI  - Commentary: Non-invasive Brain Stimulation, a Tool to Revert Maladaptive
      Plasticity in Neuropathic Pain.

PMID- 28439236
TI  - Auditory, Visual and Audiovisual Speech Processing Streams in Superior Temporal
      Sulcus.
AB  - The human superior temporal sulcus (STS) is responsive to visual and auditory
      information, including sounds and facial cues during speech recognition. We
      investigated the functional organization of STS with respect to modality-specific
      and multimodal speech representations. Twenty younger adult participants were
      instructed to perform an oddball detection task and were presented with auditory,
      visual, and audiovisual speech stimuli, as well as auditory and visual nonspeech
      control stimuli in a block fMRI design. Consistent with a hypothesized anterior
      posterior processing gradient in STS, auditory, visual and audiovisual stimuli
      produced the largest BOLD effects in anterior, posterior and middle STS (mSTS),
      respectively, based on whole-brain, linear mixed effects and principal component
      analyses. Notably, the mSTS exhibited preferential responses to multisensory
      stimulation, as well as speech compared to nonspeech. Within the mid-posterior
      and mSTS regions, response preferences changed gradually from visual, to
      multisensory, to auditory moving posterior to anterior. Post hoc analysis of
      visual regions in the posterior STS revealed that a single subregion bordering
      the mSTS was insensitive to differences in low-level motion kinematics yet
      distinguished between visual speech and nonspeech based on multi-voxel activation
      patterns. These results suggest that auditory and visual speech representations
      are elaborated gradually within anterior and posterior processing streams,
      respectively, and may be integrated within the mSTS, which is sensitive to more
      abstract speech information within and across presentation modalities. The
      spatial organization of STS is consistent with processing streams that are
      hypothesized to synthesize perceptual speech representations from sensory signals
      that provide convergent information from visual and auditory modalities.

PMID- 28439238
TI  - Rechallenge to Carboplatin in Children with Low Grade Glioma and Carboplatin
      Hypersensitivity Reactions.
AB  - Background: Carboplatin based regimens have demonstrated activity in pediatric
      patients with low grade gliomas (LGG). However, carboplatin hypersensitivity
      reactions (CHRs) may be a major problem leading to premature cessation of an
      effective therapy. The objectives of this study were to describe the prevalence,
      characteristics and management of CHR. Methods: We performed a retrospective
      review of children with LGG treated between January 1994 and July 2015 with
      carboplatin and vincristine who had a documented CHR. We identified two groups:
      the first was treated following the schema proposed by Packer et al., and re
      exposed to carboplatin using a desensitization protocol; the second was treated
      according to protocol SIOP LGG 2004 and re-exposed with the infusion time
      prolonged. Results: CHRs were observed in 16 patients (34%) out of 47.
      Hypersensitivity reactions occurred in 6 patients (20.7%) of the first, and 10
      patients (55.5%) of the second group, respectively. The grade 2 reactions were
      the most common. The median number of carboplatin doses administered at the first
      episode of CHR was 7 (range, 3-9) for the first group, and 8.5 (range, 5-11) for
      the second, respectively. Six patients were re-exposed to carboplatin using a
      desensitization protocol; 10 with a prolonged infusion time. Overall success rate
      for re-exposition was 43.75% (100% and 10%, respectively) (P = 0.001).
      Conclusions: Our results show that re-exposure is a safe alternative to
      abandoning carboplatin. Desensitization showed greater effectiveness compared to
      a prolonged infusion time, which allowed the patients to receive effective
      treatment without adverse reactions.

PMID- 28439239
TI  - Development of Automated Patch Clamp Technique to Investigate CFTR Chloride
      Channel Function.
AB  - The chloride (Cl-) channel cystic fibrosis transmembrane conductance regulator
      (CFTR) is defective in cystic fibrosis (CF), and mutation of its encoding gene
      leads to various defects such as retention of the misfolded protein in the
      endoplasmic reticulum, reduced stability at the plasma membrane, abnormal channel
      gating with low open probability, and thermal instability, which leads to
      inactivation of the channel at physiological temperature. Pharmacotherapy is one
      major therapeutic approach in the CF field and needs sensible and fast tools to
      identify promising compounds. The high throughput screening assays available are
      often fast and sensible techniques but with lack of specificity. Few works used
      automated patch clamp (APC) for CFTR recording, and none have compared
      conventional and planar techniques and demonstrated their capabilities for
      different types of experiments. In this study, we evaluated the use of planar
      parallel APC technique for pharmacological search of CFTR-trafficking correctors
      and CFTR function modulators. Using optimized conditions, we recorded both wt-
      and corrected F508del-CFTR Cl- currents with automated whole-cell patch clamp and
      compared the data to results obtained with conventional manual whole-cell patch
      clamp. We found no significant difference in patch clamp parameters such as cell
      capacitance and series resistance between automated and manual patch clamp. Also,
      the results showed good similarities of CFTR currents recording between the two
      methods. We showed that similar stimulation protocols could be used in both
      manual and automatic techniques allowing precise control of temperature, classic
      I/V relationship, and monitoring of current stability in time. In conclusion,
      parallel patch-clamp recording allows rapid and efficient investigation of CFTR
      currents with a variety of tests available and could be considered as new tool
      for medium throughput screening in CF pharmacotherapy.

PMID- 28439237
TI  - Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma.
AB  - Osteosarcoma is the most frequent malignant bone neoplasm, followed by
      chondrosarcoma and Ewing sarcoma. The diagnosis of bone neoplasms is generally
      made through histological evaluation of a biopsy. Clinical and radiological
      features are also important in aiding diagnosis and to complete the staging of
      bone cancer. In addition to these, there are several non-specific serological or
      specific molecular markers for bone neoplasms. In bone tumors, molecular markers
      increase the accuracy of the diagnosis and assist in subtyping bone tumors. Here,
      we review these markers and discuss their role in the diagnosis and prognosis of
      the three most frequent malignant bone neoplasms, namely osteosarcoma,
      chondrosarcoma, and Ewing sarcoma.

PMID- 28439240
TI  - Apolipophorin-III Acts as a Positive Regulator of Plasmodium Development in
      Anopheles stephensi.
AB  - Apolipophorin III (ApoLp-III) is a well-known hemolymph protein having a
      functional role in lipid transport and immune responses of insects. Here we
      report the molecular and functional characterization of Anopheles stephensi
      Apolipophorin-III (AsApoLp-III) gene. This gene consists of 679 nucleotides
      arranged into two exons of 45 and 540 bp that give an ORF encoding 194 amino acid
      residues. Excluding a putative signal peptide of the first 19 amino acid
      residues, the 175-residues in mature AsApoLp-III protein has a calculated
      molecular mass of 22 kDa. Phylogenetic analysis revealed the divergence of
      mosquitoes (Order Diptera) ApoLp-III from their counterparts in moths (Order:
      Lepidoptera). Also, it revealed a close relatedness of AsApoLp-III to ApoLp-III
      of An. gambiae. AsApoLp-III mRNA expression is strongly induced in Plasmodium
      berghei infected mosquito midguts suggesting its crucial role in parasite
      development. AsApoLp-III silencing decreased P. berghei oocysts numbers by 7.7
      fold against controls. These effects might be due to the interruption of AsApoLp
      III mediated lipid delivery to the developing oocysts. In addition, nitric oxide
      synthase (NOS), an antiplasmodial gene, is also highly induced in AsApoLp-III
      silenced midguts suggesting that this gene acts like an agonist and protects
      Plasmodium against the mosquito immunity.

PMID- 28439241
TI  - Nifedipine Inhibition of High-Voltage Activated Calcium Channel Currents in
      Cerebral Artery Myocytes Is Influenced by Extracellular Divalent Cations.
AB  - Voltage-dependent calcium channels (VDCCs) play an essential role in regulating
      cerebral artery diameter and it is widely appreciated that the L-type VDCC,
      CaV1.2, encoded by the CACNA1C gene, is a principal Ca2+ entry pathway in
      vascular myocytes. However, electrophysiological studies using 10 mM
      extracellular barium ([Ba2+]o) as a charge carrier have shown that ~20% of VDCC
      currents in cerebral artery myocytes are insensitive to 1,4-dihydropyridine (1,4
      DHP) L-type VDDC inhibitors such as nifedipine. Here, we investigated the
      hypothesis that the concentration of extracellular divalent cations can influence
      nifedipine inhibition of VDCC currents. Whole-cell VDCC membrane currents were
      obtained from freshly isolated rat cerebral artery myocytes in extracellular
      solutions containing Ba2+ and/or Ca2+. In the absence of [Ca2+]o, both nifedipine
      sensitive and -insensitive calcium currents were observed in 10 mM [Ba2+]o.
      However, VDCC currents were abolished by nifedipine when using a combination of
      10 mM [Ba2+]o and 100 MUM [Ca2+]o. VDCC currents were also completely inhibited
      by nifedipine in either 2 mM [Ba2+]o or 2 mM [Ca2+]o. The biophysical
      characteristics of all recorded VDCC currents were consistent with properties of
      a high-voltage activated VDCC, such as CaV1.2. Further, VDCC currents recorded in
      10 mM [Ba2+]o +/- 100 MUM [Ca2+]o or 2 mM [Ba2+]o exhibited similar sensitivity
      to the benzothiazepine L-type VDCC blocker, diltiazem, with complete current
      inhibition at 100 MUM. These data suggest that nifedipine inhibition is
      influenced by both Ca2+ binding to an external site(s) on these channels and
      surface charge effects related to extracellular divalent cations. In sum, this
      work demonstrates that the extracellular environment can profoundly impact VDCC
      current measurements.

PMID- 28439242
TI  - Comprehensive Psychopathological Assessment Based on the Association for
      Methodology and Documentation in Psychiatry (AMDP) System: Development,
      Methodological Foundation, Application in Clinical Routine, and Research.
AB  - The documentation of psychopathology is core to the clinical practice of the
      psychiatrist and clinical psychologist. However, both in initial as well as
      further training and specialization in their fields, this particular aspect of
      their work receives scanty attention only. Yet, for the past 50 years, the
      Association for Methodology and Documentation in Psychiatry (AMDP) System has
      been in existence and available as a tool to serve precisely the purpose of
      offering a systematic introduction to the terminology and documentation of
      psychopathology. The motivation for its development was based on the need for an
      assessment procedure for the reliable documentation of the effectiveness of newly
      developed psychopharmacological substances. Subsequently, the AMDP-System began
      to be applied in the context of investigations into a number of methodological
      issues in psychiatry (e.g., the frequency and specificity of particular symptoms,
      the comparison of rating scales). The System then became increasingly important
      also in clinical practice and, today, represents the most used instrument for the
      documentation of psychopathology in the German-speaking countries of Europe. This
      paper intends to offer an overview of the AMDP-System, its origins, design, and
      functionality. After an initial account of the history and development of the
      AMDP-System, the discussion will in turn focus on the System's underlying
      methodological principles, the transfer of clinical skills and competencies in
      its practical application, and its use in research and clinical practice.
      Finally, potential future areas of development in relation to the AMDP-System are
      explored.

PMID- 28439243
TI  - Relationships between Behavioural Addictions and Psychiatric Disorders: What Is
      Known and What Is Yet to Be Learned?
AB  - This article provides a narrative review of the relationships between several
      behavioural addictions [pathological gambling, problematic Internet use (PIU),
      problematic online gaming, compulsive sexual behaviour disorder, compulsive
      buying, and exercise addiction] and psychiatric disorders. Associations between
      most behavioural addictions and depressive and anxiety disorders are strong and
      seem relatively non-specific. Strong links with substance use disorders may
      support the notion that some people are more prone to addictive behaviours,
      regardless of whether these involve substances or problematic activities. Other
      associations seem relatively specific, for example, those between PIU/online
      gaming and attention-deficit/hyperactivity disorder, between compulsive buying on
      the one hand and eating disorders and hoarding on the other hand and between
      exercise addiction and eating disorders. The quality of the research varies, but
      most studies suffer from methodological limitations, including a cross-sectional
      or correlational design, non-representative study populations, small sample
      sizes, reliance on self-report assessment instruments, diverse diagnostic
      criteria, and conceptual heterogeneity of most behavioural addictions. Due to
      these limitations, generalisability of the findings is questionable and the
      direction of causality, if any, is unknown in the relationships between
      behavioural addictions and psychiatric disorders. Regardless of the aetiological
      uncertainty, these relationships often call for a modified treatment approach.
      Prospective studies are needed to clarify the longitudinal relationships between
      behavioural addictions and psychiatric disorders.

PMID- 28439244
TI  - Repeated Measures Correlation.
AB  - Repeated measures correlation (rmcorr) is a statistical technique for determining
      the common within-individual association for paired measures assessed on two or
      more occasions for multiple individuals. Simple regression/correlation is often
      applied to non-independent observations or aggregated data; this may produce
      biased, specious results due to violation of independence and/or differing
      patterns between-participants versus within-participants. Unlike simple
      regression/correlation, rmcorr does not violate the assumption of independence of
      observations. Also, rmcorr tends to have much greater statistical power because
      neither averaging nor aggregation is necessary for an intra-individual research
      question. Rmcorr estimates the common regression slope, the association shared
      among individuals. To make rmcorr accessible, we provide background information
      for its assumptions and equations, visualization, power, and tradeoffs with
      rmcorr compared to multilevel modeling. We introduce the R package (rmcorr) and
      demonstrate its use for inferential statistics and visualization with two example
      datasets. The examples are used to illustrate research questions at different
      levels of analysis, intra-individual, and inter-individual. Rmcorr is well-suited
      for research questions regarding the common linear association in paired repeated
      measures data. All results are fully reproducible.

PMID- 28439245
TI  - Validation of the Persian Version of the Langer Mindfulness Scale.
AB  - This study validates the Persian version of the Langer Mindfulness Scale (LMS).
      The original scale consists of 21 items and 4 subscales; namely, novelty
      producing, novelty seeking, engagement, and flexibility. In this study, four
      samples including 2271 individuals in total participated. Confirmatory factor
      analysis was employed to test the factorial structure of the Persian version. The
      results verified a two-factor structure including novelty producing and novelty
      seeking for the scale and the two subscales of engagement and flexibility were
      omitted due to marginal fit. The questionnaire showed satisfying psychometric
      properties in terms of reliability. Furthermore, convergent and discriminant
      validity of the instrument was examined via investigating the relationship
      between the Persian LMS with the WHOQOL instrument and negative and positive
      affect scales. The findings revealed a significant positive relationship between
      the Persian LMS and positive affect, physical health, psychological health and
      environmental health. No significant correlations were found between the LMS,
      social relationships and negative affect.

PMID- 28439246
TI  - Valuation of Go Stimuli or Devaluation of No-Go Stimuli? Evidence of an Increased
      Preference for Attended Go Stimuli Following a Go/No-Go Task.
AB  - Attentional inhibition that occurs during discrimination tasks leads to the
      negative evaluation of distractor stimuli. This phenomenon, known as the
      distractor devaluation effect also occurs when go/no-go tasks require response
      inhibition. However, it remains unclear whether there are interactions between
      attention and response controls when the distractor devaluation effect occurs.
      The aims of this study were to investigate whether attention to stimuli in the
      go/no-go task plays a facilitative role in distractor devaluation through
      response inhibition, and to clarify whether this effect reflects a decreased
      preference for no-go stimuli. Participants evaluated the preference for pictures
      before and after a go/no-go task. In Experiments 1 and 2, they made a go or no-go
      response depending on the category of pictures displayed (gummy candies or rice
      crackers), whereas in Experiment 3 they did on the basis digit category, even or
      odd numbers, superimposed on such pictures. Experiments 1 and 2 demonstrated that
      the pictures presented as no-go stimuli in the preceding go/no-go task were
      evaluated as less positive than the pictures presented as go stimuli. This
      devaluation effect reflected an increased preference for the go stimuli but not a
      decreased preference for the no-go stimuli. Experiment 3 indicated that response
      inhibition did not affect the preference for the pictures that had not received
      attention in a preceding go/no-go task. These results suggest that although
      attention plays an important role in differential ratings for go and no-go
      stimuli, such differences, in fact, reflect the valuation of go stimuli.

PMID- 28439247
TI  - When Corporate Social Responsibility (CSR) Meets Organizational Psychology: New
      Frontiers in Micro-CSR Research, and Fulfilling a Quid Pro Quo through Multilevel
      Insights.
AB  - Researchers, corporate leaders, and other stakeholders have shown increasing
      interest in Corporate Social Responsibility (CSR)-a company's discretionary
      actions and policies that appear to advance societal well-being beyond its
      immediate financial interests and legal requirements. Spanning decades of
      research activity, the scholarly literature on CSR has been dominated by meso-
      and macro-level perspectives, such as studies within corporate strategy that
      examine relationships between firm-level indicators of social/environmental
      performance and corporate financial performance. In recent years, however, there
      has been an explosion of micro-oriented CSR research conducted at the individual
      level of analysis, especially with respect to studies on how and why job seekers
      and employees perceive and react to CSR practices. This micro-level focus is
      reflected in 12 articles published as a Research Topic collection in Frontiers in
      Psychology (Organizational Psychology Specialty Section) titled "CSR and
      organizational psychology: Quid pro quo." In the present article, the authors
      summarize and integrate findings from these Research Topic articles. After
      describing some of the "new frontiers" these articles explore and create, the
      authors strive to fulfill a "quid pro quo" with some of the meso- and macro
      oriented CSR literatures that paved the way for micro-CSR research. Specifically,
      the authors draw on insights from the Research Topic articles to inform a
      multilevel model that offers multiple illustrations of how micro-level processes
      among individual stakeholders can explain variability in meso (firm)-level
      relationships between CSR practices and corporate performance. The authors also
      explore an important implication of these multilevel processes for macro-level
      societal impact.

PMID- 28439248
TI  - Effects of Promotion and Compunction Interventions on Real Intergroup
      Interactions: Promotion Helps but High Compunction Hurts.
AB  - HIGHLIGHTS  We show the promotion intervention has positive effects during
      intergroup contact, but that high levels of compunction can have negative
      effects. Intergroup contact is probably the longest standing and most
      comprehensively researched intervention to reduce discrimination. It is also part
      of ordinary social experience, and a key context in which discrimination is
      played out. In this paper, we explore two additional interventions which are also
      designed to reduce discrimination, but which have not yet been applied to real
      intergroup interactions. The promotion intervention encourages participants to
      relax and enjoy an interaction, while the compunction intervention motivates
      participants to avoid discrimination. Across two studies, we tested the separate
      effects of promotion (Study 1) and then compunction (Study 2) on participants'
      interactions with a confederate whom they believed to have a history of
      schizophrenia. In Study 1, participants received either a promotion intervention
      to "relax and have an enjoyable dialogue" or no intervention (control; n = 67).
      In Study 2, participants completed a Single-Category Implicit Attitude Test
      before being told that they were high in prejudice (high compunction condition)
      or low in prejudice (low compunction condition; n = 62). Results indicated that
      promotion was associated with broadly positive effects: participants reported
      more positive experience of the interaction (enjoyment and interest in a future
      interaction), and more positive evaluations of their contact partner (increased
      friendliness and reduced stereotyping). There were no effects on participants'
      reported intergroup anxiety. In contrast, high compunction had broadly negative
      effects: participants reported more negative experiences of the interaction and
      more negative evaluations of their contact partner (using the same dependent
      measures outlined above). In addition, participants in the high compunction
      condition reported increased intergroup anxiety and increased self-anxiety
      (anxiety around thinking or doing something that is prejudiced). Participants in
      the high compunction condition also reported reduced expectancies of self
      efficacy (i.e., they were less confident that they would be able to make a good
      impression).

PMID- 28439249
TI  - Cross-modal Action Complexity: Action- and Rule-related Memory Retrieval in Dual
      response Control.
AB  - Normally, we do not act within a single effector system only, but rather
      coordinate actions across several output modules (cross-modal action). Such cross
      modal action demands can vary substantially with respect to their complexity in
      terms of the number of task-relevant response combinations and to-be-retrieved
      stimulus-response (S-R) mapping rules. In the present study, we study the impact
      of these two types of cross-modal action complexity on dual-response costs (i.e.,
      performance differences between single- and dual-action demands). In Experiment
      1, we combined a manual and an oculomotor task, each involving four response
      alternatives. Crucially, one (unconstrained) condition involved all 16 possible
      combinations of response alternatives, whereas a constrained condition involved
      only a subset of possible response combinations. The results revealed that
      preparing for a larger number of response combinations yielded a significant, but
      moderate increase in dual-response costs. In Experiment 2, we utilized one common
      lateralized auditory (e.g., left) stimulus to trigger incompatible response
      compounds (e.g., left saccade and right key press or vice versa). While one
      condition only involved one set of task-relevant S-R rules, another condition
      involved two sets of task-relevant rules (coded by stimulus type: noise/tone),
      while the number of task-relevant response combinations was the same in both
      conditions. Here, an increase in the number of to-be-retrieved S-R rules was
      associated with a substantial increase in dual-response costs that were also
      modulated on a trial-by-trial basis when switching between rules. Taken together,
      the results shed further light on the dependency of cross-modal action control on
      both action- and rule-related memory retrieval processes.

PMID- 28439250
TI  - Differential Impact of Visuospatial Working Memory on Rule-based and Information
      integration Category Learning.
AB  - Previous studies have indicated that the category learning system is a mechanism
      with multiple processing systems, and that working memory has different effects
      on category learning. But how does visuospatial working memory affect perceptual
      category learning? As there is no definite answer to this question, we conducted
      three experiments. In Experiment 1, the dual-task paradigm with sequential
      presentation was adopted to investigate the influence of visuospatial working
      memory on rule-based and information-integration category learning. The results
      showed that visuospatial working memory interferes with rule-based but not
      information-integration category learning. In Experiment 2, the dual-task
      paradigm with simultaneous presentation was used, in which the categorization
      task was integrated into the visuospatial working memory task. The results
      indicated that visuospatial working memory affects information-integration
      category learning but not rule-based category learning. In Experiment 3, the dual
      task paradigm with simultaneous presentation was employed, in which visuospatial
      working memory was integrated into the category learning task. The results
      revealed that visuospatial working memory interferes with both rule-based and
      information-integration category learning. Through these three experiments, we
      found that, regarding the rule-based category learning, working memory load is
      the main mechanism by which visuospatial working memory influences the discovery
      of the category rules. In addition, regarding the information-integration
      category learning, visual resources mainly operates on the category
      representation.

PMID- 28439251
TI  - When a Fly Ball Is Out of Reach: Catchability Judgments Are Not Based on Optical
      Acceleration Cancelation.
AB  - The optical acceleration cancelation (OAC) strategy, based on Chapman's (1968)
      analysis of the outfielder problem, has been the dominant account for the control
      of running to intercept fly balls approaching head on. According to the OAC
      strategy, outfielders will arrive at the interception location just in time to
      catch the ball when they keep optical acceleration zero. However, the affordance
      aspect of this task, that is, whether or not an approaching fly ball is
      catchable, is not part of this account. The present contribution examines whether
      the scope of the OAC strategy can be extended to also include the affordance
      aspect of running to catch a fly ball. This is done by considering a fielder's
      action boundaries (i.e., maximum running velocity and -acceleration) in the
      context of the OAC strategy. From this, only when running velocity is maximal and
      optical acceleration is non-zero, a fielder would use OAC to perceive a fly ball
      as uncatchable. The present contribution puts this hypothesis to the test.
      Participants were required to try to intercept fly balls projected along their
      sagittal plane. Some fly balls were catchable whereas others were not.
      Participants were required to catch as many fly balls as possible and to call
      'no' when they perceived a fly ball to be uncatchable. Participants' running
      velocity and -acceleration at the moment of calling 'no' were examined. Results
      showed that participants' running velocity was submaximal before or while calling
      'no'. Also running acceleration was often submaximal. These results cannot be
      explained by the use of OAC in judging catchability and ultimately call for a new
      strategy of locomotor control in running to catch a fly ball.

PMID- 28439252
TI  - Response: Commentary: Pupil old/new effects reflect stimulus encoding and
      decoding in short-term memory.

PMID- 28439254
TI  - Distinct Conformational Dynamics of Three G Protein-Coupled Receptors Measured
      Using FlAsH-BRET Biosensors.
AB  - A number of studies have profiled G protein-coupled receptor (GPCR) conformation
      using fluorescent biaresenical hairpin binders (FlAsH) as acceptors for BRET or
      FRET. These conformation-sensitive biosensors allow reporting of movements
      occurring on the intracellular surface of a receptor to investigate mechanisms of
      receptor activation and function. Here, we generated eight FlAsH-BRET-based
      biosensors within the sequence of the beta2-adrenergic receptor (beta2AR) and
      compared agonist-induced responses to the angiotensin II receptor type I (AT1R)
      and the prostaglandin F2alpha receptor (FP). Although all three receptors had
      FlAsH-binding sequences engineered into the third intracellular loops and
      carboxyl-terminal domain, both the magnitude and kinetics of the BRET responses
      to ligand were receptor-specific. Biosensors in ICL3 of both the AT1R and FP
      responded robustly when stimulated with their respective full agonists as opposed
      to the beta2AR where responses in the third intracellular loop were weak and
      transient when engaged by isoproterenol. C-tail sensors responses were more
      robust in the beta2AR and AT1R but not in FP. Even though GPCRs share the
      heptahelical topology and are expressed in the same cellular background,
      different receptors have unique conformational fingerprints.

PMID- 28439253
TI  - Secondary Hematoma Expansion and Perihemorrhagic Edema after Intracerebral
      Hemorrhage: From Bench Work to Practical Aspects.
AB  - Intracerebral hemorrhages (ICH) represent about 10-15% of all strokes per year in
      the United States alone. Key variables influencing the long-term outcome after
      ICH are hematoma size and growth. Although death may occur at the time of the
      hemorrhage, delayed neurologic deterioration frequently occurs with hematoma
      growth and neuronal injury of the surrounding tissue. Perihematoma edema has also
      been implicated as a contributing factor for delayed neurologic deterioration
      after ICH. Cerebral edema results from both blood-brain barrier disruption and
      local generation of osmotically active substances. Inflammatory cellular
      mediators, activation of the complement, by-products of coagulation and hemolysis
      such as thrombin and fibrin, and hemoglobin enter the brain and induce a local
      and systemic inflammatory reaction. These complex cascades lead to apoptosis or
      neuronal injury. By identifying the major modulators of cerebral edema after ICH,
      a therapeutic target to counter degenerative events may be forthcoming.

PMID- 28439255
TI  - Assessing the Functional Role of Leptin in Energy Homeostasis and the Stress
      Response in Vertebrates.
AB  - Leptin is a pleiotropic hormone that plays a critical role in regulating
      appetite, energy metabolism, growth, stress, and immune function across
      vertebrate groups. In mammals, it has been classically described as an adipostat,
      relaying information regarding energy status to the brain. While retaining poor
      sequence conservation with mammalian leptins, teleostean leptins elicit a number
      of similar regulatory properties, although current evidence suggests that it does
      not function as an adipostat in this group of vertebrates. Teleostean leptin also
      exhibits functionally divergent properties, however, possibly playing a role in
      glucoregulation similar to what is observed in lizards. Further, leptin has been
      recently implicated as a mediator of immune function and the endocrine stress
      response in teleosts. Here, we provide a review of leptin physiology in
      vertebrates, with a particular focus on its actions and regulatory properties in
      the context of stress and the regulation of energy homeostasis.

PMID- 28439256
TI  - The Role of Endocrine G Protein-Coupled Receptors in Ovarian Cancer Progression.
AB  - Ovarian cancer is the seventh most common cancer in women and the most lethal
      gynecological cancer, causing over 151,000 deaths worldwide each year.
      Dysregulated production of endocrine hormones, known to have pluripotent effects
      on cell function through the activation of receptor signaling pathways, is
      believed to be a high-risk factor for ovarian cancer. An increasing body of
      evidence suggests that endocrine G protein-coupled receptors (GPCRs) are involved
      in the progression and metastasis of ovarian neoplasms. GPCRs are attractive drug
      targets because their activities are regulated by more than 25% of all drugs
      approved by the Food and Drug Administration. Therefore, understanding the role
      of endocrine GPCRs during ovarian cancer progression and metastasis will allow
      for the development of novel strategies to design effective chemotherapeutic
      drugs against malignant ovarian tumors. In this review, we address the signaling
      pathways and functional roles of several key endocrine GPCRs that are related to
      the cause, progression, and metastasis of ovarian cancer.

PMID- 28439257
TI  - High-Resolution Recording of the Circadian Oscillator in Primary Mouse alpha- and
      beta-Cell Culture.
AB  - Circadian clocks have been developed in evolution as an anticipatory mechanism
      allowing for adaptation to the constantly changing light environment due to
      rotation of the Earth. This mechanism is functional in all light-sensitive
      organisms. There is a considerable body of evidence on the tight connection
      between the circadian clock and most aspects of physiology and metabolism.
      Clocks, operative in the pancreatic islets, have caught particular attention in
      the last years due to recent reports on their critical roles in regulation of
      insulin secretion and etiology of type 2 diabetes. While beta-cell clocks have
      been extensively studied during the last years, alpha-cell clocks and their role
      in islet function and orchestration of glucose metabolism stayed unexplored,
      largely due to the difficulty to isolate alpha-cells, which represents a
      considerable technical challenge. Here, we provide a detailed description of an
      experimental approach for the isolation of separate mouse alpha- and beta-cell
      population, culture of isolated primary alpha- and beta-cells, and their
      subsequent long-term high-resolution circadian bioluminescence recording. For
      this purpose, a triple reporter ProGlucagon-Venus/RIP-Cherry/Per2:Luciferase
      mouse line was established, carrying specific fluorescent reporters for alpha-
      and beta-cells, and luciferase reporter for monitoring the molecular clockwork.
      Flow cytometry fluorescence-activated cell sorting allowed separating pure alpha-
      and beta-cell populations from isolated islets. Experimental conditions,
      developed by us for the culture of functional primary mouse alpha- and beta-cells
      for at least 10 days, will be highlighted. Importantly, temporal analysis of
      freshly isolated alpha- and beta-cells around-the-clock revealed preserved
      rhythmicity of core clock genes expression. Finally, we describe the setting to
      assess circadian rhythm in cultured alpha- and beta-cells synchronized in vitro.
      The here-described methodology allows to analyze the functional properties of
      primary alpha- and beta-cells under physiological or pathophysiological
      conditions and to assess the islet cellular clock properties.

PMID- 28439259
TI  - Increased Biological Activity of Aneurinibacillus migulanus Strains Correlates
      with the Production of New Gramicidin Secondary Metabolites.
AB  - The soil-borne gram-positive bacteria Aneurinibacillus migulanus strain Nagano
      shows considerable potential as a biocontrol agent against plant diseases. In
      contrast, A. migulanus NCTC 7096 proved less effective for inhibition of plant
      pathogens. Nagano strain exerts biocontrol activity against some gram-positive
      and gram-negative bacteria, fungi and oomycetes through the production of
      gramicidin S (GS). Apart from the antibiotic effects, GS increases the rate of
      evaporation from the plant surface, reducing periods of surface wetness and
      thereby indirectly inhibiting spore germination. To elucidate the molecular basis
      of differential biocontrol abilities of Nagano and NCTC 7096, we compared GS
      production and biosurfactant secretion in addition to genome mining of the
      genomes. Our results proved that: (i) Using oil spreading, blood agar lysis,
      surface tension and tomato leaves wetness assays, Nagano showed increased
      biosurfactant secretion in comparison with NCTC 7096, (ii) Genome mining
      indicated the presence of GS genes in both Nagano and NCTC 7096 with two amino
      acid units difference between the strains: T342I and P419S. Using 3D models and
      the DUET server, T342I and P419S were predicted to decrease the stability of the
      NCTC 7096 GS synthase, (iii) Nagano produced two additional GS-like molecules GS
      1155 (molecular weight 1155) and GS-1169 (molecular weight 1169), where one or
      two ornithine residues replace lysine in the peptide. There was also a negative
      correlation between surface tension and the quantity of GS-1169 present in
      Nagano, and (iv) the Nagano genome had a full protein network of
      exopolysaccharide biosynthesis in contrast to NCTC 7096 which lacked the first
      enzyme of the network. NCTC 7096 is unable to form biofilms as observed for
      Nagano. Different molecular layers, mainly gramicidin secondary metabolite
      production, account for differential biocontrol abilities of Nagano and NCTC
      7096. This work highlighted the basis of differential biological control
      abilities between strains belonging to the same species and demonstrates
      techniques useful to the screening of effective biocontrol strains for
      environmentally friendly secondary metabolites that can be used to manage plant
      pathogens in the field.

PMID- 28439258
TI  - Diabetic Cardiomyopathy: An Immunometabolic Perspective.
AB  - The heart possesses a remarkable inherent capability to adapt itself to a wide
      array of genetic and extrinsic factors to maintain contractile function. Failure
      to sustain its compensatory responses results in cardiac dysfunction, leading to
      cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left
      ventricular hypertrophy and reduced diastolic function, with or without
      concurrent systolic dysfunction in the absence of hypertension and coronary
      artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic
      reticulum stress, formation of extracellular matrix proteins, and advanced
      glycation end products constitute the early stage in DCM. These early events are
      followed by steatosis (accumulation of lipid droplets) in cardiomyocytes, which
      is followed by apoptosis, changes in immune responses with a consequent increase
      in fibrosis, remodeling of cardiomyocytes, and the resultant decrease in cardiac
      function. The heart is an omnivore, metabolically flexible, and consumes the
      highest amount of ATP in the body. Altered myocardial substrate and energy
      metabolism initiate the development of DCM. Diabetic hearts shift away from the
      utilization of glucose, rely almost completely on fatty acids (FAs) as the energy
      source, and become metabolically inflexible. Oxidation of FAs is metabolically
      inefficient as it consumes more energy. In addition to metabolic inflexibility
      and energy inefficiency, the diabetic heart suffers from impaired calcium
      handling with consequent alteration of relaxation-contraction dynamics leading to
      diastolic and systolic dysfunction. Sarcoplasmic reticulum (SR) plays a key role
      in excitation-contraction coupling as Ca2+ is transported into the SR by the
      SERCA2a (sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a) during cardiac
      relaxation. Diabetic cardiomyocytes display decreased SERCA2a activity and leaky
      Ca2+ release channel resulting in reduced SR calcium load. The diabetic heart
      also suffers from marked downregulation of novel cardioprotective microRNAs
      (miRNAs) discovered recently. Since immune responses and substrate energy
      metabolism are critically altered in diabetes, the present review will focus on
      immunometabolism and miRNAs.

PMID- 28439261
TI  - Interaction of Bacterial Membrane Vesicles with Specific Species and Their
      Potential for Delivery to Target Cells.
AB  - Membrane vesicles (MVs) are secreted from a wide range of microbial species and
      transfer their content to other cells. Although MVs play critical roles in
      bacterial communication, whether MVs selectively interact with bacterial cells in
      microbial communities is unclear. In this study, we investigated the specificity
      of the MV-cell interactions and evaluated the potential of MVs to target
      bacterial cells for delivery. MV association with bacterial cells was examined
      using a fluorescent membrane dye to label MVs. MVs derived from the
      enterobacterium Buttiauxella agrestis specifically interacted with cells of the
      parent strain but interacted less specifically with those of other genera tested
      in this study. Electron microscopic analyses showed that MVs were not only
      attached on B. agrestis cells but also fused to them. The interaction energy,
      which was characterized by hydrodynamic diameter and zeta potential based on the
      Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, was significant low between MVs
      and cells in B. agrestis, compared to those between B. agrestis MVs and cells of
      other genera. Similar specific interaction was also occurred between B. agrestis
      MVs and cells of six other species belonging to Buttiauxella spp. B. agrestis
      harboring plasmid pBBR1MCS-1 secreted plasmid-containing MVs (p-MVs), and plasmid
      DNA in p-MVs was transferred to the same species. Moreover, antibiotic-associated
      MVs enabled effective killing of target species; the survival rate of B. agrestis
      was lower than those of Escherichia coli and Pseudomonas aeruginosa in the
      presence of gentamicin-associated MVs derived from B. agrestis. Altogether, we
      provide the evidence that MVs selectively interact with target bacterial cells
      and offer a new avenue for controlling specific bacterial species using bacterial
      MVs in microbial communities.

PMID- 28439260
TI  - Intriguing Interaction of Bacteriophage-Host Association: An Understanding in the
      Era of Omics.
AB  - Innovations in next-generation sequencing technology have introduced new avenues
      in microbial studies through "omics" approaches. This technology has considerably
      augmented the knowledge of the microbial world without isolation prior to their
      identification. With an enormous volume of bacterial "omics" data, considerable
      attempts have been recently invested to improve an insight into virosphere. The
      interplay between bacteriophages and their host has created a significant
      influence on the biogeochemical cycles, microbial diversity, and bacterial
      population regulation. This review highlights various concepts such as genomics,
      transcriptomics, proteomics, and metabolomics to infer the phylogenetic
      affiliation and function of bacteriophages and their impact on diverse microbial
      communities. Omics technologies illuminate the role of bacteriophage in an
      environment, the influences of phage proteins on the bacterial host and provide
      information about the genes important for interaction with bacteria. These
      investigations will reveal some of bio-molecules and biomarkers of the novel
      phage which demand to be unveiled.

PMID- 28439262
TI  - Turn Up the Heat-Food and Clinical Escherichia coli Isolates Feature Two
      Transferrable Loci of Heat Resistance.
AB  - Heat treatment is a widely used process to reduce bacterial loads in the food
      industry or to decontaminate surfaces, e.g., in hospital settings. However, there
      are situations where lower temperatures must be employed, for instance in case of
      food production such as raw milk cheese or for decontamination of medical devices
      such as thermo-labile flexible endoscopes. A recently identified locus of heat
      resistance (LHR) has been shown to be present in and confer heat resistance to a
      variety of Enterobacteriaceae, including Escherichia coli isolates from food
      production settings and clinical ESBL-producing E. coli isolates. Here, we
      describe the presence of two distinct LHR variants within a particularly heat
      resistant E. coli raw milk cheese isolate. We demonstrate for the first time in
      this species the presence of one of these LHRs on a plasmid, designated
      pFAM21805, also encoding type 3 fimbriae and three bacteriocins and corresponding
      self-immunity proteins. The plasmid was highly transferable to other E. coli
      strains, including Shiga-toxin-producing strains, and conferred LHR-dependent
      heat resistance as well as type 3 fimbriae-dependent biofilm formation
      capabilities. Selection for and acquisition of this "survival" plasmid by
      pathogenic organisms, e.g., in food production environments, may pose great
      concern and emphasizes the need to screen for the presence of LHR genes in
      isolates.

PMID- 28439264
TI  - Benthic Diatom Based Indices for Water Quality Assessment in Two Subtropical
      Streams.
AB  - Benthic diatoms have been universally used as indicators to assess water quality
      in lotic ecosystems. However, most diatom-based indices developed in Europe have
      not been widely used or tested in other continents such as Asia or Oceania. This
      study compared the performance of 14 widely-applied diatom indices in assessing
      ecological conditions in subtropical streams in South East Queensland (SEQ) in
      Australia and in the upper Han River in China. Most water quality variables in
      the upper Han River including dissolved organic carbon (DOC), total nitrogen
      (TN), and soluble reactive phosphorus (SRP) had strong relationships with at
      least one diatom index, with the exception of IDAP (Index Diatom Artois
      Picardie), and TDI (Trophic Diatom Index). However, in SEQ, most of the
      environmental variables including DOC, ammonia nitrogen (NH4-N), TN, SRP, and
      electrical conductivity (EC) showed no significant relationships with diatom
      indices, and the DI-CH (Swiss Diatom Index) and WAT (Watanabe's Index) were
      unrelated to any of the variables examined. Only pH and nitrite or nitrate
      nitrogen (NOX-N) were significant predictors of several diatom indices in SEQ,
      especially TID (Rott trophic index). In the upper Han River, much of the spatial
      variation in most diatom indices was explained by proximate determinants alone,
      including EC, DOC, dissolved oxygen (DO) or SRP, or a combination of ultimate
      (canopy, forest) and proximate factors (R2 in most models> 0.75). Most diatom
      indices performed as predicted in the upper Han River where nutrient and organic
      matter pollution was relatively high, and variation in pH low. However, the
      indices performed poorly in SEQ where the water quality gradient was low and
      instead most responded to spatial variation in pH. This finding serves as a
      caution to the application of diatom indices in river basins that fall outside of
      the range of water quality values of the systems in which they originally
      developed.

PMID- 28439263
TI  - Microbial Diversity of Browning Peninsula, Eastern Antarctica Revealed Using
      Molecular and Cultivation Methods.
AB  - Browning Peninsula is an ice-free polar desert situated in the Windmill Islands,
      Eastern Antarctica. The entire site is described as a barren landscape, comprised
      of frost boils with soils dominated by microbial life. In this study, we explored
      the microbial diversity and edaphic drivers of community structure across this
      site using traditional cultivation methods, a novel approach the soil substrate
      membrane system (SSMS), and culture-independent 454-tag pyrosequencing. The
      measured soil environmental and microphysical factors of chlorine, phosphate,
      aspect and elevation were found to be significant drivers of the bacterial
      community, while none of the soil parameters analyzed were significantly
      correlated to the fungal community. Overall, Browning Peninsula soil harbored a
      distinctive microbial community in comparison to other Antarctic soils comprised
      of a unique bacterial diversity and extremely limited fungal diversity. Tag
      pyrosequencing data revealed the bacterial community to be dominated by
      Actinobacteria (36%), followed by Chloroflexi (18%), Cyanobacteria (14%), and
      Proteobacteria (10%). For fungi, Ascomycota (97%) dominated the soil microbiome,
      followed by Basidiomycota. As expected the diversity recovered from culture-based
      techniques was lower than that detected using tag sequencing. However, in the
      SSMS enrichments, that mimic the natural conditions for cultivating oligophilic
      "k-selected" bacteria, a larger proportion of rare bacterial taxa (15%), such as
      Blastococcus, Devosia, Herbaspirillum, Propionibacterium and Methylocella and
      fungal (11%) taxa, such as Nigrospora, Exophiala, Hortaea, and Penidiella were
      recovered at the genus level. At phylum level, a comparison of OTU's showed that
      the SSMS shared 21% of Acidobacteria, 11% of Actinobacteria and 10% of
      Proteobacteria OTU's with soil. For fungi, the shared OTUs was 4% (Basidiomycota)
      and <0.5% (Ascomycota). This was the first known attempt to culture microfungi
      using the SSMS which resulted in an increase in diversity from 14 to 57
      microfungi OTUs compared to standard cultivation. Furthermore, the SSMS offers
      the opportunity to retrieve a greater diversity of bacterial and fungal taxa for
      future exploitation.

PMID- 28439265
TI  - Bacterial and Fungal Community Structures in Loess Plateau Grasslands with
      Different Grazing Intensities.
AB  - The Loess Plateau of China is one of the most fragile ecosystems worldwide; thus,
      human production activities need to be conducted very cautiously. In this study,
      MiSeq high-throughput sequencing was applied to assess the relationship between
      bacterial and fungal community structures and changes in vegetation and soil
      physical and chemical properties induced by grazing, in four grasslands with
      different levels of grazing intensity (0, 2.67, 5.33, and 8.67 sheep/ha) in the
      semiarid region of the Loess Plateau. The relative abundances of the bacterial
      community in the grasslands with 2.67 and 5.33 sheep/ha were significantly higher
      than those in grasslands with 0 and 8.67 sheep/ha, and the fungal diversity was
      significantly lower for grasslands with 2.67 sheep/ha than for the other
      grasslands. Redundancy analysis (RDA) showed that plant biomass, nitrate, and
      total nitrogen have significant effects on bacterial community structure, whereas
      nitrate and total nitrogen also significantly affect fungal community structure.
      Variation partitioning showed that soil and plant characteristics influence the
      bacterial and fungal community structures; these characteristics explained 51.9
      and 52.9% of the variation, respectively. Thus, bacterial and fungal community
      structures are very sensitive to grazing activity and change to different extents
      with different grazing intensities. Based on our findings, a grazing intensity of
      about 2.67 sheep/ha is considered the most appropriate in semiarid grassland of
      the Loess Plateau.

PMID- 28439266
TI  - A Novel Regulator of Activation-Induced Cytidine Deaminase/APOBECs in Immunity
      and Cancer: Schrodinger's CATalytic Pocket.
AB  - Activation-induced cytidine deaminase (AID) and its relative APOBEC3 cytidine
      deaminases boost immune response by mutating immune or viral genes. Because of
      their genome-mutating activities, AID/APOBECs are also drivers of tumorigenesis.
      Due to highly charged surfaces, extensive non-specific protein-protein/nucleic
      acid interactions, formation of polydisperse oligomers, and general insolubility,
      structure elucidation of these proteins by X-ray crystallography and NMR has been
      challenging. Hence, almost all available AID/APOBEC structures are of mutated
      and/or truncated versions. In 2015, we reported a functional structure for AID
      using a combined computational-biochemical approach. In so doing, we described a
      new regulatory mechanism that is a first for human DNA/RNA-editing enzymes. This
      mechanism involves dynamic closure of the catalytic pocket. Subsequent X-ray and
      NMR studies confirmed our discovery by showing that other APOBEC3s also close
      their catalytic pockets. Here, we highlight catalytic pocket closure as an
      emerging and important regulatory mechanism of AID/APOBEC3s. We focus on three
      sub-topics: first, we propose that variable pocket closure rates across
      AID/APOBEC3s underlie differential activity in immunity and cancer and review
      supporting evidence. Second, we discuss dynamic pocket closure as an ever-present
      internal regulator, in contrast to other proposed regulatory mechanisms that
      involve extrinsic binding partners. Third, we compare the merits of classical
      approaches of X-ray and NMR, with that of emerging computational-biochemical
      approaches, for structural elucidation specifically for AID/APOBEC3s.

PMID- 28439267
TI  - Pulmonary Delivery of Virosome-Bound Antigen Enhances Antigen-Specific CD4+ T
      Cell Proliferation Compared to Liposome-Bound or Soluble Antigen.
AB  - Pulmonary administration of biomimetic nanoparticles loaded with antigen may
      represent an effective strategy to directly modulate adaptive immune responses in
      the respiratory tract. Depending on the design, virosomes may not only serve as
      biomimetic antigen carriers but are also endowed with intrinsic immune
      stimulatory properties. We designed fluorescently labeled influenza-derived
      virosomes and liposome controls coupled to the model antigen ovalbumin to
      investigate uptake, phenotype changes, and antigen processing by antigen
      presenting cells exposed to such particles in different respiratory tract
      compartments. Both virosomes and liposomes were captured by pulmonary macrophages
      and dendritic cells alike and induced activation in particle-bearing cells by
      upregulation of costimulatory markers such as CD40, CD80, CD86, PD-L1, PD-L2, and
      ICOS-L. Though antigen processing and accumulation of both coupled and soluble
      antigen was similar between virosomes and liposomes, only ovalbumin-coupled
      virosomes generated a strong antigen-specific CD4+ T cell proliferation.
      Pulmonary administrated antigen-coupled virosomes therefore effectively induced
      adaptive immune responses and may be utilized in novel preventive or therapeutic
      approaches in the respiratory tract.

PMID- 28439268
TI  - Alveolar Fluid Clearance in Pathologically Relevant Conditions: In Vitro and In
      Vivo Models of Acute Respiratory Distress Syndrome.
AB  - Critically ill patients with respiratory failure from acute respiratory distress
      syndrome (ARDS) have reduced ability to clear alveolar edema fluid. This
      reduction in alveolar fluid clearance (AFC) contributes to the morbidity and
      mortality in ARDS. Thus, it is important to understand why AFC is reduced in ARDS
      in order to design targeted therapies. In this review, we highlight experiments
      that have advanced our understanding of ARDS pathogenesis, with particular
      reference to the alveolar epithelium. First, we review how vectorial ion
      transport drives the clearance of alveolar edema fluid in the uninjured lung.
      Next, we describe how alveolar edema fluid is less effectively cleared in lungs
      affected by ARDS and describe selected in vitro and in vivo experiments that have
      elucidated some of the molecular mechanisms responsible for the reduced AFC.
      Finally, we describe one potential therapy that targets this pathway: bone marrow
      derived mesenchymal stem (stromal) cells (MSCs). Based on preclinical studies,
      MSCs enhance AFC and promote the resolution of pulmonary edema and thus may offer
      a promising cell-based therapy for ARDS.

PMID- 28439269
TI  - Genome-Wide Identification of Target Genes for the Key B Cell Transcription
      Factor Ets1.
AB  - BACKGROUND: The transcription factor Ets1 is highly expressed in B lymphocytes.
      Loss of Ets1 leads to premature B cell differentiation into antibody-secreting
      cells (ASCs), secretion of autoantibodies, and development of autoimmune disease.
      Despite the importance of Ets1 in B cell biology, few Ets1 target genes are known
      in these cells. RESULTS: To obtain a more complete picture of the function of
      Ets1 in regulating B cell differentiation, we performed Ets1 ChIP-seq in primary
      mouse B cells to identify >10,000-binding sites, many of which were localized
      near genes that play important roles in B cell activation and differentiation.
      Although Ets1 bound to many sites in the genome, it was required for regulation
      of less than 5% of them as evidenced by gene expression changes in B cells
      lacking Ets1. The cohort of genes whose expression was altered included numerous
      genes that have been associated with autoimmune disease susceptibility. We
      focused our attention on four such Ets1 target genes Ptpn22, Stat4, Egr1, and
      Prdm1 to assess how they might contribute to Ets1 function in limiting ASC
      formation. We found that dysregulation of these particular targets cannot explain
      altered ASC differentiation in the absence of Ets1. CONCLUSION: We have
      identified genome-wide binding targets for Ets1 in B cells and determined that a
      relatively small number of these putative target genes require Ets1 for their
      normal expression. Interestingly, a cohort of genes associated with autoimmune
      disease susceptibility is among those that are regulated by Ets1. Identification
      of the target genes of Ets1 in B cells will help provide a clearer picture of how
      Ets1 regulates B cell responses and how its loss promotes autoantibody secretion.

PMID- 28439270
TI  - Cytokine-Regulation of Na+-K+-Cl- Cotransporter 1 and Cystic Fibrosis
      Transmembrane Conductance Regulator-Potential Role in Pulmonary Inflammation and
      Edema Formation.
AB  - Pulmonary edema, a major complication of lung injury and inflammation, is defined
      as accumulation of extravascular fluid in the lungs leading to impaired diffusion
      of respiratory gases. Lung fluid balance across the alveolar epithelial barrier
      protects the distal airspace from excess fluid accumulation and is mainly
      regulated by active sodium transport and Cl- absorption. Increased hydrostatic
      pressure as seen in cardiogenic edema or increased vascular permeability as
      present in inflammatory lung diseases such as the acute respiratory distress
      syndrome (ARDS) causes a reversal of transepithelial fluid transport resulting in
      the formation of pulmonary edema. The basolateral expressed Na+-K+-2Cl-
      cotransporter 1 (NKCC1) and the apical Cl- channel cystic fibrosis transmembrane
      conductance regulator (CFTR) are considered to be critically involved in the
      pathogenesis of pulmonary edema and have also been implicated in the inflammatory
      response in ARDS. Expression and function of both NKCC1 and CFTR can be modulated
      by released cytokines; however, the relevance of this modulation in the context
      of ARDS and pulmonary edema is so far unclear. Here, we review the existing
      literature on the regulation of NKCC1 and CFTR by cytokines, and-based on the
      known involvement of NKCC1 and CFTR in lung edema and inflammation-speculate on
      the role of cytokine-dependent NKCC1/CFTR regulation for the pathogenesis and
      potential treatment of pulmonary inflammation and edema formation.

PMID- 28439271
TI  - Cross Talk between Inhibitory Immunoreceptor Tyrosine-Based Activation Motif
      Signaling and Toll-Like Receptor Pathways in Macrophages and Dendritic Cells.
AB  - The innate immune cells sense microbial infection and self-ligands by pathogen
      recognition receptors (PRRs), such as toll-like receptors (TLRs) and regulatory
      receptors (RRs), associated with immunoreceptor tyrosine-based activation motif
      (ITAM). Rapid activation and concerted action of PRRs signaling and feedback
      inhibitory mechanisms must be engaged to ensure the host defense functions and to
      prevent cytotoxicity associated with excessive activation. ITAM-associated RRs
      can generate stimulatory or, paradoxically, inhibitory signals. The network of
      ITAM-associated RR, together with TLR-signaling pathways, are responsible for
      immunogenic or tolerogenic responses of macrophages and dendritic cells to their
      microenvironment. In macrophages, TLR4 signaling is inhibited by low-avidity
      ligation of ITAM-associated receptors, while high-avidity ligation of ITAM
      associated receptors results in potentiation of TLR4 signaling together with
      resistance to extracellular cytokine microenvironment signals. In contrast to
      macrophages, TLR7/9 signaling in plasmacytoid DCs (pDCs) is inhibited by high
      avidity ligation of ITAM-associated RR, while low-avidity ligation does not show
      any effect. Surprisingly, interference of ITAM-associated receptor signaling with
      TLR pathways has not been reported in conventional dendritic cells. Here, we
      present an overview of molecular mechanisms acting at the crossroads of TLR and
      ITAM-signaling pathways and address the question of how the high-avidity
      engagement of the ITAM-associated receptors in pDCs inhibits TLR7/9 signaling.
      Cellular context and spatiotemporal engagement of ITAM- and TLR-signaling
      pathways are responsible for different outcomes of macrophage versus pDC
      activation. While the cross-regulation of cytokine and TLR signaling, together
      with antigen presentation, are the principal functions of ITAM-associated RR in
      macrophages, the major role of these receptors in pDCs seems to be related to
      inhibition of cytokine production and reestablishment of a tolerogenic state
      following pDC activation. Pharmacologic targeting of TLR and ITAM signaling could
      be an attractive new therapeutic approach for treatment of chronic infections,
      cancer, and autoimmune and inflammatory diseases related to pDCs.

PMID- 28439273
TI  - Expansion of FasL-Expressing CD5+ B Cells in Type 1 Diabetes Patients.
AB  - Fas ligand drives insulitis in the non-obese diabetic mouse model of type 1
      diabetes (T1D) and negatively regulates IL-10-producing (IL-10pos) CD5+ B cells
      in pancreata. Relevance of these phenomena to the human disease is poorly
      understood. Here, using splenocytes from T1D, autoantibody (Ab+), and non
      diabetic (ND) human subjects, we show that a subpopulation of CD5+ B cells that
      is characterized by expression of FasL (FasLhiCD5+) was significantly elevated in
      T1D subjects, many of whom had significantly reduced frequency of IL-10posCD5+ B
      cells compared to Ab+ subjects. The majority of FasLhiCD5+ B cells did not
      produce cytokines and were more highly resistant to activation-induced cell death
      than their IL-10posCD5+ counterparts. These results associate expansion of FasL
      expressing CD5+ B cells with T1D and lay the groundwork for future mechanistic
      studies to understand specific role in disease pathogenesis.

PMID- 28439274
TI  - Complete Genome Sequence of Lactobacillus casei LC5, a Potential Probiotics for
      Atopic Dermatitis.

PMID- 28439275
TI  - Arabidopsis ALA1 and ALA2 Mediate RNAi-Based Antiviral Immunity.
AB  - RNA intereferencing (RNAi) pathway regulates antiviral immunity and mediates
      plant growth and development. Despite considerable research efforts, a few
      components in RNAi pathway have been revealed, including ARGONAUTEs (AGOs), DICER
      LIKEs (DCLs), RNA-dependent RNA polymerase 1 and 6 (RDR1/6), and ALTERED MERISTEM
      PROGRAM 1 (AMP1). In this study, we performed a forward genetic screening for
      enhancers of rdr6 via inoculation of CMV2aTDelta2b, a 2b-deficient Cucumber
      Mosaic Virus that is unable to suppress RNAi-mediated antiviral immunity. We
      uncover that the membrane-localized flippase Aminophospholipid ATPase 1 (ALA1)
      cooperates with RDR6 and RDR1 to promote antiviral immunity and regulate
      fertility in Arabidopsis. Moreover, we find that ALA2, a homolog of ALA1, also
      participates in antiviral immunity. Our findings suggest that ALA1 and ALA2 act
      as novel components in the RNAi pathway and function additively with RDR1 and
      RDR6 to mediate RNAi-based antiviral immunity and plant development.

PMID- 28439272
TI  - The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases.
AB  - Autoimmune thyroid diseases (AITD) are a group of both B cell- and T cell
      mediated organ-specific autoimmune diseases. Graves' disease and Hashimoto
      thyroiditis are the two main clinical presentations of AITD. Both genetic and
      environmental factors have important roles in the development of AITD.
      Epigenetics have been considered to exert key roles in integrating those genetic
      and environmental factors, and epigenetic modifications caused by environmental
      factors may drive genetically susceptibility individuals to develop AITD. Recent
      studies on the epigenetics of AITD have provided some novel insights into the
      pathogenesis of AITD. The aim of this review is to provide an overview of recent
      advances in the epigenetic mechanisms of AITD, such as DNA methylation, histone
      modifications, and non-coding RNAs. This review highlights the key roles of
      epigenetics in the pathogenesis of AITD and potential clinical utility. However,
      the epigenetic roles in AITD are still not fully elucidated, and more researches
      are needed to provide further deeper insights into the roles of epigenetics in
      AITD and to uncover new therapeutic targets. Although there are many studies
      assessing the epigenetic modifications in AITD patients, the clinical utility of
      epigenetics in AITD remains poorly defined. More studies are needed to identify
      the underlying epigenetic modifications that can contribute to accurate diagnosis
      of AITD, adequate choice of treatment approach, and precise prediction of
      treatment outcomes.

PMID- 28439276
TI  - Transcriptome Comparison Reveals the Adaptive Evolution of Two Contrasting
      Ecotypes of Zn/Cd Hyperaccumulator Sedum alfredii Hance.
AB  - Hyperaccumulating ecotype (HE) and non-hyperaccumulating ecotype (NHE) of Sedum
      alfredii Hance belong to the same species but exhibit contrasting characteristics
      regarding hyperaccumulation and hypertolerance to cadmium and zinc. The Illumina
      Hiseq 2500 platform was employed to sequence HE and NHE to study the genetic
      evolution of this contrasting trait. Greater than 90 million clean reads were
      obtained and 118,479/228,051 unigenes of HE/NHE were annotated based on seven
      existing databases. We identified 149,668/319,830 single nucleotide polymorphisms
      (SNPs) and 12,691/14,428 simple sequence repeats (SSRs) of HE/NHE. We used a
      branch-site model to identify 18 divergent orthologous genes and 57 conserved
      orthologous genes of S. alfredii Hance. The divergent orthologous genes were
      mainly involved in the transcription and translation processes, protein
      metabolism process, calcium (Ca2+) pathway, stress response process and signal
      transduction process. To the best of our knowledge, this is the first study to
      use RNA-seq to compare the genetic evolution of hyperaccumulating and non
      hyperaccumulating plants from the same species. In addition, this study made the
      sole concrete for further studies on molecular markers and divergent orthologous
      genes to depict the evolution process and formation of the hyperaccumulation and
      hypertolerance traits in S. alfredii Hance.

PMID- 28439277
TI  - Expression of Pennisetum glaucum Eukaryotic Translational Initiation Factor 4A
      (PgeIF4A) Confers Improved Drought, Salinity, and Oxidative Stress Tolerance in
      Groundnut.
AB  - Eukaryotic translational initiation factor 4A belong to family of helicases,
      involved in multifunctional activities during stress and non-stress conditions.
      The eIF4A gene was isolated and cloned from semi-arid cereal crop of Pennisetum
      glaucum. In present study, the PgeIF4A gene was expressed under the regulation of
      stress inducible Arabidopsis rd29A promoter in groundnut (cv JL-24) with bar as a
      selectable marker. The de-embryonated cotyledons were infected with Agrobacterium
      tumefaciens (LBA4404) carrying rd29A:PgeIF4A construct and generated high
      frequency of multiple shoots in phosphinothricin medium. Twenty- four T0 plants
      showed integration of both nos-bar and rd29A-PgeIF4A gene cassettes in genome
      with expected amplification products of 429 and 654 bps, respectively. Transgene
      copy number integration was observed in five T0 transgenic plants through
      Southern blot analysis. Predicted Mendelian ratio of segregation (3:1) was noted
      in transgenic plants at T1 generation. The T2 homozygous lines (L1-5, L8-2, and
      L16-2) expressing PgeIF4A gene were exhibited superior growth performance with
      respect to phenotypic parameters like shoot length, tap root length, and lateral
      root formation under simulated drought and salinity stresses compared to the wild
      type. In addition, the chlorophyll retention was found to be higher in these
      plants compared to the control plants. The quantitative real time-PCR results
      confirmed higher expression of PgeIF4A gene in L1-5, L8-3, and L16-2 plants
      imposed with drought/salt stress. Further, the salt stress tolerance was
      associated with increase in oxidative stress markers, such as superoxide
      dismutase accumulation, reactive oxygen species scavenging, and membrane
      stability in transgenic plants. Taken together our results confirmed that the
      PgeIF4A gene expressing transgenic groundnut plants exhibited better adaptation
      to stress conditions.

PMID- 28439278
TI  - Exploration of Elite Stilbene Synthase Alleles for Resveratrol Concentration in
      Wild Chinese Vitis spp. and Vitis Cultivars.
AB  - Resveratrol contributes to a plant's tolerance of various abiotic and biotic
      stresses and is highly beneficial to human health. A search for elite alleles
      affecting resveratrol production was undertaken to find useful grapevine
      germplasm resources. Resveratrol levels in both berry skins and leaves were
      determined in 95 grapevine accessions (including 50 wild Chinese grapevine
      accessions and 45 cultivars) during two consecutive years. Resveratrol contents
      were higher in berry skins than in leaves and in wild Chinese grapevines than in
      grapevine cultivars. Using genotyping data, 79 simple sequence repeat (SSR)
      markers linked to 44 stilbene synthase (STS) genes were detected in the 95
      accessions, identifying 40 SSR markers with higher polymorphisms. Eight SSR
      marker loci, encompassing 19 alleles, were significantly associated with
      resveratrol content on (P < 0.001), and 5 SSR loci showed repeated associations.
      Locus Sh5 had four associations: three positive for allele 232 (including leaves
      in the 2 years) and one negative for allele 236 in four environments. Loci Sh9
      and Sh56 for a total of 7 alleles exhibited positive effects in berry skins in
      the 2 years. In berry skins, locus Sh56 with positive effects was closely linked
      to VvSTS27, and locus Sh77 with negative effects to VvSTS17, importantly, the two
      candidate genes both were located on Chromosome 16. The SSR marker loci and
      candidate genes identified in this study will provide a useful basis for future
      molecular breeding for increased production of natural resveratrol and its
      derivatives.

PMID- 28439279
TI  - Metabolic Investigation of Phelipanche aegyptiaca Reveals Significant Changes
      during Developmental Stages and in Its Different Organs.
AB  - Phelipanche aegyptiaca Pers. is a root holoparasitic plant considered to be among
      the most destructive agricultural weeds worldwide. In order to gain more
      knowledge about the metabolic profile of the parasite during its developmental
      stages, we carried out primary metabolic and lipid profiling using GC-MS
      analysis. In addition, the levels of amino acids that incorporate into proteins,
      total protein in the albumin fraction, nitrogen, reduced sugars, and phenols were
      determined. For the assays, the whole plants from the four developmental stages
      tubercle, pre-emergent shoot, post-emergent shoot, and mature flowering plants
      were taken. Thirty-five metabolites out of 66 differed significantly between the
      various developmental stages. The results have shown that the first three
      developmental stages were distinguished in their profiles, but the latter two did
      not differ from the mature stage. Yet, 46% of the metabolites detected did not
      change significantly during the developmental stages. This is unlike other
      studies of non-parasitic plants showing that their metabolic levels tend to alter
      significantly during development. This implies that the parasite can control the
      levels of these metabolites. We further studied the metabolic nature of five
      organs (adventitious roots, lower and upper shoot, floral buds, and flowers) in
      mature plants. Similar to non-parasitic plants, the parasite exhibited
      significant differences between the vegetative and reproductive organs. Compared
      to other organs, floral buds had higher levels of free amino acids and total
      nitrogen, whereas flowers accumulated higher levels of simple sugars such as
      sucrose, and the putative precursors for nectar synthesis, color, and volatiles.
      This suggests that the reproductive organs have the ability to accumulate
      metabolites that are required for the production of seeds and as a source of
      energy for the reproductive processes. The data contribute to our knowledge about
      the metabolic behavior of parasites that rely on their host for its basic
      nutrients.

PMID- 28439280
TI  - Insights on Structure and Function of a Late Embryogenesis Abundant Protein from
      Amaranthus cruentus: An Intrinsically Disordered Protein Involved in Protection
      against Desiccation, Oxidant Conditions, and Osmotic Stress.
AB  - Late embryogenesis abundant (LEA) proteins are part of a large protein family
      that protect other proteins from aggregation due to desiccation or osmotic
      stresses. Recently, the Amaranthus cruentus seed proteome was characterized by 2D
      PAGE and one highly accumulated protein spot was identified as a LEA protein and
      was named AcLEA. In this work, AcLEA cDNA was cloned into an expression vector
      and the recombinant protein was purified and characterized. AcLEA encodes a 172
      amino acid polypeptide with a predicted molecular mass of 18.34 kDa and estimated
      pI of 8.58. Phylogenetic analysis revealed that AcLEA is evolutionarily close to
      the LEA3 group. Structural characteristics were revealed by nuclear magnetic
      resonance and circular dichroism methods. We have shown that recombinant AcLEA is
      an intrinsically disordered protein in solution even at high salinity and osmotic
      pressures, but it has a strong tendency to take a secondary structure, mainly
      folded as alpha-helix, when an inductive additive is present. Recombinant AcLEA
      function was evaluated using Escherichia coli as in vivo model showing the
      important protection role against desiccation, oxidant conditions, and osmotic
      stress. AcLEA recombinant protein was localized in cytoplasm of Nicotiana
      benthamiana protoplasts and orthologs were detected in seeds of wild and
      domesticated amaranth species. Interestingly AcLEA was detected in leaves, stems,
      and roots but only in plants subjected to salt stress. This fact could indicate
      the important role of AcLEA protection during plant stress in all amaranth
      species studied.

PMID- 28439281
TI  - L-Theanine Content and Related Gene Expression: Novel Insights into Theanine
      Biosynthesis and Hydrolysis among Different Tea Plant (Camellia sinensis L.)
      Tissues and Cultivars.
AB  - L-Theanine content has tissues and cultivars specificity in tea plant (Camellia
      sinensis L.), the correlations of theanine metabolic related genes expression
      profiles with theanine contents were explored in this study. L-theanine contents
      in the bud and 1st leaf, 2nd leaf, 3rd leaf, old leaf, stem, and lateral root
      were determined by HPLC from three C. sinensis cultivars, namely 'Huangjinya',
      'Anjibaicha', and 'Yingshuang', respectively. The theanine contents in leaves and
      root of 'Huangjinya' were the highest, followed by 'Anjibaicha', and
      'Yingshuang'. The theanine contents in the leaves reduced as the leaf mature
      gradually, and in stem were the least. Seventeen genes encoding enzymes involved
      in theanine metabolism were identified from GenBank and our tea transcriptome
      database, including CsTS1, CsTS2, CsGS1, CsGS2, CsGOGAT-Fe, CsGOGAT-NAD(P)H,
      CsGDH1, CsGDH2, CsALT, CsSAMDC, CsADC, CsCuAO, CsPAO, CsNiR, CsNR, CsGGT1, and
      CsGGT3. The transcript profiles of those seventeen genes in the different tissues
      of three tea plant cultivars were analyzed comparatively. Among the different
      cultivars, the transcript levels of most selected genes in 'Huangjinya' were
      significantly higher than that in the 'Anjibaicha' and 'Yingshuang'. Among the
      different tissues, the transcript levels of CsTS2, CsGS1, and CsGDH2 almost
      showed positive correlation with the theanine contents, while the other genes
      showed negative correlation with the theanine contents in most cases. The
      theanine contents showed correlations with related genes expression levels among
      cultivars and tissues of tea plant, and were determined by the integrated effect
      of the metabolic related genes.

PMID- 28439282
TI  - Overexpression of Cucumber Phospholipase D alpha Gene (CsPLDalpha) in Tobacco
      Enhanced Salinity Stress Tolerance by Regulating Na+-K+ Balance and Lipid
      Peroxidation.
AB  - Plant phospholipase D (PLD), which can hydrolyze membrane phospholipids to
      produce phosphatidic acid (PA), a secondary signaling molecule, has been proposed
      to function in diverse plant stress responses. In this research, we characterized
      the roles of the cucumber phospholipase D alpha gene (PLDalpha, GenBank accession
      number EF363796) in growth and tolerance to short- and long-term salt stress in
      transgenic tobacco (Nicotiana tabacum). Fresh and dry weights of roots, PLD
      activity and content, mitogen activated protein kinase (MAPK) gene expression,
      Na+-K+ homeostasis, expression of genes encoding ion exchange, reactive oxygen
      species (ROS) metabolism and osmotic adjustment substances were investigated in
      wild type (WT) and CsPLDalpha-overexpression tobacco lines grown under short- and
      long-term high salt (250 mM) stress. Under short-term stress (5 h), in both
      overexpression lines, the PA content, and the expression levels of MAPK and
      several genes related to ion exchange (NtNHX1, NtNKT1, NtHAK1, NtNHA1, NtVAG1),
      were promoted by high PLD activity. Meanwhile, the Na+/K+ ratio decreased. Under
      long-term stress (16 days), ROS scavenging systems (superoxide dismutase,
      peroxidase, catalase, ascorbate peroxidase activities) in leaves of transgenic
      lines were more active than those in WT plants. Meanwhile, the contents of
      proline, soluble sugar, and soluble protein significantly increased. In contrast,
      the contents of O2*- and H2O2, the electrolytic leakage and the accumulation of
      malondialdehyde in leaves significantly decreased. The root fresh and dry weights
      of the overexpression lines increased significantly. Na+-K+ homeostasis had the
      same trend as under the short-term treatment. These findings suggested that
      CsPLDalpha-produced PA can activate the downstream signals' adaptive response to
      alleviate the damage of salt stress, and the main strategies for adaptation to
      salt stress are the accumulation of osmoprotective compounds, maintaining Na+-K+
      homeostasis and the scavenging of ROS, which function in the osmotic balancing
      and structural stabilization of membranes.

PMID- 28439283
TI  - Floral Mass per Area and Water Maintenance Traits Are Correlated with Floral
      Longevity in Paphiopedilum (Orchidaceae).
AB  - Floral longevity (FL) determines the balance between pollination success and
      flower maintenance. While a longer floral duration enhances the ability of plants
      to attract pollinators, it can be detrimental if it negatively affects overall
      plant fitness. Longer-lived leaves display a positive correlation with their dry
      mass per unit area, which influences leaf construction costs and physiological
      functions. However, little is known about the association among FL and floral dry
      mass per unit area (FMA) and water maintenance traits. We investigated whether
      increased FL might incur similar costs. Our assessment of 11 species of
      Paphiopedilum (slipper orchids) considered the impact of FMA and flower water
      maintenance characteristics on FL. We found a positive relationship between FL
      and FMA. Floral longevity showed significant correlations with osmotic potential
      at the turgor loss and bulk modulus of elasticity but not with FA. Neither the
      size nor the mass per area was correlated between leaves and flowers, indicating
      that flower and leaf economic traits evolved independently. Therefore, our
      findings demonstrate a clear relationship between FL and the capacity to maintain
      water status in the flower. These economic constraints also indicate that
      extending the flower life span can have a high physiological cost in
      Paphiopedilum.

PMID- 28439284
TI  - The Translation Initiation Factor 1A (TheIF1A) from Tamarix hispida Is Regulated
      by a Dof Transcription Factor and Increased Abiotic Stress Tolerance.
AB  - Eukaryotic translation initiation factor 1A (eIF1A) functions as an mRNA scanner
      and AUG initiation codon locator. However, few studies have clarified the role of
      eIF1A in abiotic stress. In this study, we cloned eIF1A (TheIF1A) from Tamarix
      hispida and found its expression to be induced by NaCl and polyethylene glycol
      (PEG) in roots, stems, and leaves. Compared to control, TheIF1A root expression
      was increased 187.63-fold when exposed to NaCl for 6 h, suggesting a potential
      abiotic stress response for this gene. Furthermore, transgenic tobacco plants
      overexpressing TheIF1A exhibited enhanced seed germination and a higher total
      chlorophyll content under salt and mannitol stresses. Increased superoxide
      dismutase, peroxidase, glutathione transferase and glutathione peroxidase
      activities, as well as decreased electrolyte leakage rates and malondialdehyde
      contents, were observed in TheIF1A-transgenic tobacco and T. hispida seedlings
      under salt and mannitol stresses. Histochemical staining suggested that TheIF1A
      improves reactive oxygen species (ROS) scavenging in plants. Moreover, TheIF1A
      may regulate expression of stress-related genes, including TOBLTP, GST, MnSOD,
      NtMPK9, poxN1, and CDPK15. Moreover, a 1352-bp promoter fragment of TheIF1A was
      isolated, and cis-elements were identified. Yeast one-hybrid assays showed that
      ThDof can specifically bind to the Dof motif present in the promoter. In
      addition, ThDof showed expression patterns similar to those of TheIF1A under NaCl
      and PEG stresses. These findings suggest the potential mechanism and
      physiological roles of TheIF1A. ThDof may be an upstream regulator of TheIF1A,
      and TheIF1A may function as a stress response regulator to improve plant salt and
      osmotic stress tolerance via regulation of associated enzymes and ROS scavenging,
      thereby reducing cell damage under stress conditions.

PMID- 28439285
TI  - A Quantitative Proteomic Analysis of Brassinosteroid-induced Protein
      Phosphorylation in Rice (Oryza sativa L.).
AB  - The group of polyhydroxysteroid phytohormones referred to as the brassinosteroids
      (BRs) is known to act on plant development and the stress response. BR signal
      transduction relies largely on protein phosphorylation. By employing a label
      free, MS (Mass Spectrometry)-based phosphoproteomic approach, we report here the
      largest profiling of 4,034 phosphosites on 1,900 phosphoproteins from rice young
      seedlings and their dynamic response to BR. 1,821 proteins, including kinases,
      transcription factors and core components of BR and other hormone signaling
      pathways, were found to be differentially phosphorylated during the BR treatment.
      A Western blot analysis verified the differential phosphorylation of five of
      these proteins, implying that the MS-based phosphoproteomic data were robust. It
      is proposed that the dephosphorylation of gibberellin (GA) signaling components
      could represent an important mechanism for the BR-regulated antagonism to GA, and
      that BR influences the plant architecture of rice by regulating cellulose
      synthesis via phosphorylation.

PMID- 28439286
TI  - SNP Discovery and Genetic Variation of Candidate Genes Relevant to Heat Tolerance
      and Agronomic Traits in Natural Populations of Sand Rice (Agriophyllum
      squarrosum).
AB  - The extreme stress tolerance and high nutritional value of sand rice
      (Agriophyllum squarrosum) make it attractive for use as an alternative crop in
      response to concerns about ongoing climate change and future food security.
      However, a lack of genetic information hinders understanding of the mechanisms
      underpinning the morphological and physiological adaptations of sand rice. In the
      present study, we sequenced and analyzed the transcriptomes of two individuals
      representing semi-arid [Naiman (NM)] and arid [Shapotou (SPT)] sand rice
      genotypes. A total of 105,868 pairwise single nucleotide polymorphisms (SNPs)
      distributed in 24,712 Unigenes were identified among SPT and NM samples; the
      average SNP frequency was 0.3% (one SNP per 333 base pair). Characterization of
      gene annotation demonstrated that variations in genes involved in DNA
      recombination were associated with the survival of the NM population in the semi
      arid environment. A set of genes predicted to be relevant to heat stress response
      and agronomic traits was functionally annotated using the accumulated knowledge
      from Arabidopsis and several crop plants, including rice, barley, maize, and
      sorghum. Four candidate genes related to heat tolerance (heat-shock transcription
      factor, HsfA1d), seed size (DA1-Related, DAR1), and flowering (early flowering 3,
      ELF3 and late elongated hypocotyl, LHY) were subjected to analysis of the genetic
      diversity in 10 natural populations, representing the core germplasm resource
      across the area of sand rice distribution in China. Only one SNP was detected in
      each of HsfA1d and DAR1, among 60 genotypes, with two in ELF3 and four in LHY.
      Nucleotide diversity ranged from 0.00032 to 0.00118. Haplotype analysis indicated
      that the NM population carried a specific allele for all four genes, suggesting
      that divergence has occurred between NM and other populations. These four genes
      could be further analyzed to determine whether they are associated with phenotype
      variation and identify alleles favorable for sand rice breeding.

PMID- 28439287
TI  - Rattlesnake Crotalus molossus nigrescens venom induces oxidative stress on human
      erythrocytes.
AB  - BACKGROUND: Globally, snake envenomation is a well-known cause of death and
      morbidity. In many cases of snakebite, myonecrosis, dermonecrosis, hemorrhage and
      neurotoxicity are present. Some of these symptoms may be provoked by the
      envenomation itself, but others are secondary effects of the produced oxidative
      stress that enhances the damage produced by the venom toxins. The only oxidative
      stress effect known in blood is the change in oxidation number of Fe (from
      ferrous to ferric) in hemoglobin, generating methemoglobin but not in other
      macromolecules. Currently, the effects of the overproduction of methemoglobin
      derived from snake venom are not extensively recorded. Therefore, the present
      study aims to describe the oxidative stress induced by Crotalus molossus
      nigrescens venom using erythrocytes. METHODS: Human erythrocytes were washed and
      incubated with different Crotalus molossus nigrescens venom concentrations (0-640
      MUg/mL). After 24 h, the hemolytic activity was measured followed by attenuated
      total reflectance-Fourier transform infrared spectroscopy, non-denaturing PAGE,
      conjugated diene and thiobarbituric acid reactive substances determination.
      RESULTS: Low concentrations of venom (<10 MUg/mL) generates oxyhemoglobin release
      by hemolysis, whereas higher concentrations produced a hemoglobin shift of
      valence, producing methemoglobin (>40 MUg/mL). This substance is not degraded by
      proteases present in the venom. By infrared spectroscopy, starting in 80 MUg/mL,
      we observed changes in bands that are associated with protein damage (1660 and
      1540 cm-1) and lipid peroxidation (2960, 2920 and 1740 cm-1). Lipid peroxidation
      was confirmed by conjugated diene and thiobarbituric acid reactive substance
      determination, in which differences were observed between the control and
      erythrocytes treated with venom. CONCLUSIONS: Crotalus molossus nigrescens venom
      provokes hemolysis and oxidative stress, which induces methemoglobin formation,
      loss of protein structure and lipid peroxidation.

PMID- 28439288
TI  - Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of
      vascular collapse: response to disodium cromoglycate and disease outcome.
AB  - BACKGROUND: Mastocytosis are rare diseases characterized by an accumulation of
      clonal mast cells (MCs) in one or multiple organs or tissues. Patients with
      systemic mastocytosis (SM), whose MCs frequently arbor the activating D816V KIT
      mutation, may have indolent to aggressive diseases, and they may experience MC
      mediator related symptoms. Indolent SM with recurrent anaphylaxis or vascular
      collapse in the absence of skin lesions, ISMs(-), is a specific subtype indolent
      SM (ISM), and this clonal MC activation disorder represents a significant
      fraction of all MC activation syndromes. The V560G KIT mutation is extremely rare
      in patients with SM and its biological and prognostic impact remains unknown.
      CASE PRESENTATION: A 15-year old boy was referred to our hospital because of
      repeated episodes of flushing, hypotension and syncope since the age of 3-years,
      preceded by skin lesions compatible with mastocytosis on histopathology that had
      disappeared in the late-early childhood. Diagnosis of ISM, more precisely the
      ISMs(-) variant, was confirmed based on the clinical manifestations together with
      increased baseline serum tryptase levels and the presence of morphologically
      atypical, mature appearing (CD117+high, FcepsilonRI+) phenotypically aberrant
      (CD2+, CD25+) MCs, expressing activation-associated markers (CD63, CD69), in the
      bone marrow. Molecular genetic studies revealed the presence of the KIT V560G
      mutation in bone marrow MCs, but not in other bone marrow cells, whereas the
      screening for mutations in codon 816 of KIT was negative. The patient was treated
      with oral disodium cromoglycate and the disease had a favorable outcome after an
      eleven-year follow-up period, during which progressively lower serum tryptase
      levels together with the fully disappearance of all clinical manifestations was
      observed. CONCLUSIONS: To the best of our knowledge this first report of a
      patient with ISM, whose bone marrow MCs carry the KIT V560G activating mutation,
      manifesting as recurrent spontaneous episodes of flushing and vascular collapse
      in the absence of skin lesions at the time of diagnosis, in whom disodium
      cromoglycate had led to long term clinical remission.

PMID- 28439289
TI  - Bipolarity and suicidal ideation in children and adolescents: a systematic review
      with meta-analysis.
AB  - BACKGROUND: Affective disorders in children and adolescents have received growing
      attention in the world scenario of mental health. Additionally, there has been an
      increasing prevalence of suicidal ideation in this population. OBJECTIVE: A
      systematic review with meta-analysis was conducted to demonstrate the main risk
      factors regarding the development of suicidal ideation in the bipolar disorder.
      METHODS: This is a systematic review with meta-analysis using the PRISMA protocol
      (http://www.prisma-statement.org/). This study included secondary data. Original
      data in mental health were collected by mapping the evidence found in the
      following electronic databases: MEDLINE/PubMed, LILACS, SciELO, and ScienceDirect
      in the period from 2005 to 2015. RESULTS: We found 1418 registrations in such
      databases, and 46 of them were selected to comprise this review. The result
      introduces a joint risk between the studies of 2.94 CI [2.29-3.78]. A significant
      correlation was verified between the risk factors and the suicidal ideation. The
      result was r (Pearson) = 0.7103 and p value <0.001. CONCLUSION: Children and
      adolescents living with bipolar disorder are more vulnerable to suicidal
      ideation. These results reinforce the need of a more effective public policy
      directed toward this population.

PMID- 28439290
TI  - Predictors of exclusive breastfeeding duration among 6-12 month aged children in
      gurage zone, South Ethiopia: a survival analysis.
AB  - BACKGROUND: Exclusive breastfeeding is giving only breast milk to an infant from
      birth up to six months of age, with the exception of medications and vitamins.
      For the first six months of life, breast milk alone is the ideal nourishment to
      meet the nutritional demand of the growing child. Although breastfeeding is a
      universal practice, in Ethiopia only 52% of children aged less than six months
      old were exclusively breastfed. The study aimed to investigate the predictors of
      exclusive breastfeeding duration among women who had children aged between 6-12
      months in Gurage zone, South Ethiopia. METHODS: A mixed method cross-sectional
      study was conducted to assess predictors of exclusive breastfeeding duration in
      south Ethiopia. Eight hundred and twenty eight study participants were recruited
      using a multistage sampling technique for the quantitative survey. Interviewer
      administered close ended questionnaire was used to collect the quantitative data.
      Data were entered using Epi Data and analyzed using SPSS version 21. The Kaplan
      Meier curve with log rank test was used to compare the survival difference due to
      the selected covariates. A binary and multivariable Cox regression model was used
      to identify the independent predictors of exclusive breastfeeding duration. Three
      focus group discussions were conducted to generate the qualitative data.
      Qualitative data is transcribed and analyzed by thematic approach using open-code
      software. RESULTS: The median duration of exclusive breastfeeding was six months.
      About 21.9% of women introduced complementary food before six months of child
      age. Women with education status of diploma and above (Adjusted Hazard Ratio
      [AHR]: 2.89, 95% CI: 1.05, 7.97), perceived inadequate breast milk (AHR: 11, 95%
      CI: 6.7, 18.0) and cesarean section delivery (AHR: 3.8, 95% CI: 2.0, 7.2) were
      more likely to cease exclusive breastfeeding before six months of child age;
      while women who had infant feeding counseling during postnatal care (AHR: 5.1,
      95% CI: 2.5, 10.23) were less likely to cease exclusive breastfeeding before the
      child was six months of age. CONCLUSIONS: A significant proportion of women cease
      exclusive breastfeeding before the recommended six months duration. Maternal
      education of diploma and above, perceived inadequacy of breast milk, cesarean
      section delivery, postnatal counseling on child feeding are factors significantly
      associated with the duration of exclusive breastfeeding. Encouraging behavioral
      change and improving communication regarding the duration of exclusive
      breastfeeding, and increasing the utilization of postnatal counseling about
      exclusive breastfeeding are recommended.

PMID- 28439291
TI  - Breastfeeding counseling and support are associated with continuous exclusive
      breastfeeding from one week to six months of age among HIV exposed infants in
      north Gondar zone, Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Globally, exclusive breastfeeding prevents 1.3 million child deaths
      and has an added benefit for people living with the Human Immune Deficiency Virus
      (HIV) by preventing mother-to-child transmission of HIV. However, literature is
      scarce in Ethiopia; therefore this study aimed to assess the rate of continuous
      exclusive breastfeeding from the end of the first week to 6 months of age, among
      HIV exposed infants (aged 7-20 months) who were followed up in government
      hospitals of North Gondar Zone, Ethiopia, and associated factors. METHODS: An
      institutional based cross-sectional study was conducted from February 21 to March
      30, 2016. All mother-child pairs (367) attending the chronic HIV care clinic in
      government hospitals of North Gondar Zone were included in the study. Exclusive
      breastfeeding was defined as the practice of feeding only breast milk (including
      expressed breast milk) during the first 6 months and no other liquids and solid
      foods except medications. However since prelacteal feeding is a deep rooted norm
      in the study setting, we report continuous exclusive breastfeeding from the end
      of first week to 6 months of age of infants, ignoring all prelacteal feeding
      offered at birth. A binary multivariable logistic regression analysis was
      employed to identify factors associated with exclusive breastfeeding. RESULTS:
      The overall prevalence of continuous exclusive breastfeeding among HIV exposed
      infants was 86.4%. According to the multivariable analysis; breastfeeding
      counseling (Adjusted Odds Ratio [AOR] = 5.1, 95% Confidence Interval [CI] 1.4,
      18.2), breastfeeding support (AOR = 3.7, 95% CI 1.3, 10.5), and not experiencing
      obstetric problems (AOR = 3.4, 95% CI: 1.3, 8.8) were associated with higher odds
      of continuous breastfeeding. CONCLUSIONS: In this study, most HIV exposed infants
      were continuously breastfed from the end of first week to 6 months of age.
      Breastfeeding counseling, breastfeeding support and experiencing obstetric
      problems were identified as significant determinants of continuous breastfeeding.
      Therefore, breastfeeding counseling and support should be strengthened to improve
      the coverage of optimal exclusive breastfeeding practice. Moreover, prompt
      diagnosis and treatment of obstetric problems should be initiated.

PMID- 28439292
TI  - Effects of Bushen Tianjing Recipe in a rat model of tripterygium glycoside
      induced premature ovarian failure.
AB  - BACKGROUND: Bushen Tianjing Recipe (BTR) is a traditional Chinese herbal medicine
      that has been prescribed for premature ovarian failure (POF) for decades in
      China. Nevertheless, little is known regarding its underlying molecular
      mechanism. In the present study, we investigated the effects of BTR in a
      tripterygium glycoside (TG)-induced-POF rat model. METHODS: Three doses of BTR
      were administered via intragastric gavage to adult female Sprague-Dawley (SD)
      rats with TG-induced POF. After 15 days of treatment, the estrous cycle was
      examined by vaginal smear analysis. Serum levels of estradiol, follicle
      stimulating hormone, progesterone, and testosterone were measured by
      radioimmunoassay. Histological analysis and assessment of apoptosis were
      performed after hematoxylin and eosin staining of ovarian tissue sections. The
      expression of vascular endothelial growth factor (VEGF), vascular endothelial
      growth factor receptor 2 (VEGFR2), anti-apoptotic factor Bcl-2, and pro-apoptotic
      factors Bax and caspase 3 in ovaries of animals was examined by an
      immunohistochemistry process. RESULTS: BTR not only reverted an abnormal estrous
      cycle and decreased the ovary index in POF rats but also improved the abnormal
      secretion of reproductive hormones associated with POF. In addition, treatment
      with BTR can protect ovaries from TG-induced damage, induce intraovarian
      expression of VEGF and VEGFR2, and regulate intraovarian expression of apoptosis
      related proteins. CONCLUSIONS: Our results show that BTR is effective in the
      treatment of TG-induced POF rats. Promotion of angiogenesis and anti-apoptosis
      are most likely to contribute to the effects of BTR against POF.

PMID- 28439293
TI  - Socio-demographic characteristics, clinical profile and prevalence of existing
      mental illness among suicide attempters attending emergency services at two
      hospitals in Hawassa city, South Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Suicide is a major public health problem worldwide. It contributes
      for more than one million deaths each year. Since previous suicidal attempt was
      considered as the best predictor of future suicide, identifying factors behind
      suicidal attempt are helpful to design suicide prevention strategies. The aim of
      this study was to assess socio-demographic characteristics, clinical profile and
      prevalence of existing mental illness among patients presenting with suicidal
      attempt to emergency services of general hospitals in South Ethiopia. METHODS: We
      conducted a cross-sectional study on patients presenting with complications of
      suicidal attempt to emergency departments of two general hospitals in Hawassa
      city from November, 2014 to August, 2015. Data was collected using semi
      structured questionnaire which contained socio-demographic and clinical
      variables. The Mini International Neuropsychiatric Interview version 5 (MINI
      PLUs) was used to assess the prevalence of existing mental illness among study
      participants. Data was entered and analyzed using IBM SPSS statistics 21 software
      package. RESULTS: A total of 96 individuals were assessed, of whom 56 (58.3%)
      were females. The mean age of study participants was 21.5 (8.0) years. The
      majority, 75 (78.1%), of the study participants were aged below 25 years.
      Ingesting pesticide poisons and corrosive agent were used by the majority to
      attempt suicide. Mental illness was found in only three (3.1%) of the study
      participants. Impulsivity (the time between decision to attempt suicide and the
      actual attempt of less than 5 min) was reported by 30 (31.2%) of the study
      participants, of whom 18 (60%) were males. Males were found three times more
      likely to attempt suicide impulsively than women (COR = 3.0, 95% CI 1.2-7.3).
      Quarreling with family members, facing financial crisis, and having unplanned and
      unwanted pregnancy were reported by the majority of study participants as
      immediate reasons to attempt suicide. CONCLUSIONS: The presence of stressful life
      events and impulsivity behind suicidal behavior of the younger generation implies
      that designing suicide prevention strategies for this group is crucial. Moreover,
      further research is needed to systematically examine the relationship between the
      presence of mental illness and suicidal attempt with a larger sample size and
      more robust methodology.

PMID- 28439294
TI  - Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar.
AB  - BACKGROUND: Biomass pretreatment remains an essential step in lignocellulosic
      biofuel production, largely to facilitate the efficient removal of lignin and
      increase enzyme accessibility to the polysaccharides. In recent years, there have
      been significant efforts in planta to reduce lignin content or modify its
      composition to overcome the inherent recalcitrance that it imposes on
      lignocellulosic biomass during processing. Here, transgenic poplar lines in which
      monolignol ferulate conjugates were synthesized during cell wall development to
      introduce, during lignification, readily cleavable ester linkages into the lignin
      polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were
      pretreated with different ionic liquids (ILs). RESULTS: The strategic
      introduction of ester bonds into the lignin backbone resulted in increased
      pretreatment efficiency and released more carbohydrates with lower energy input.
      After pretreatment with any of three different ILs, and after limited
      saccharification, the transgenic poplars, especially those with relatively higher
      amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher
      sugar levels compared to WT plants. CONCLUSION: Our findings clearly demonstrate
      that the introduction of ester linkages into the lignin polymer backbone
      decreases biomass recalcitrance in poplar has the potential to reduce the energy
      and/or amount of IL required for effective pretreatment, and could enable the
      development of an economically viable and sustainable biorefinery process.

PMID- 28439295
TI  - Production of high-concentration n-caproic acid from lactate through fermentation
      using a newly isolated Ruminococcaceae bacterium CPB6.
AB  - BACKGROUND: n-Caproic acid (CA), as a medium-chain carboxylic acid, is a valuable
      chemical feedstock for various industrial applications. The fermentative
      production of CA from renewable carbon sources has attracted a lot of attentions.
      Lactate is a significant intermediate waste in the anaerobic breakdown of
      carbohydrates that comprise 18-70% of the chemical oxygen demand (COD) in
      municipal and some industrial wastewaters. Recently, researchers (including our
      own group) reported the CA production using lactate as electron donor with newly
      identified microbiome systems. However, within such processes, it was hard to
      determine whether the CA production was completed by a single strain or by the co
      metabolism of different microorganisms. RESULTS: Here, we report the CA
      production using lactate as electron donor using the strain CPB6, which we
      isolated from a microbiome for CA production as described previously. Strain CPB6
      is affiliated with Clostridium cluster IV of the family of Ruminococcaceae based
      on 16S rRNA gene sequence analysis. The strain prefers acidic initial pH
      condition (pH 5.0-6.5), and the temperature ranging from 30 to 40  degrees C for
      CA production. In a fed-batch fermentation with non-sterilized lactate-containing
      organic wastewater as feedstock, strain CPB6 produced 16.6 g/L CA (from 45.1 g/L
      lactate) with a maximum productivity of 5.29 g/L/day. Enzyme assays with crude
      cell extract showed that CPB6 can metabolize acetate and butyryl-CoA to produce n
      butyric acid, and acetate/n-butyrate and caproyl-CoA to produce CA, respectively.
      CONCLUSION: This study demonstrated that high concentration of CA production can
      be obtained by a newly isolated pure culture CPB6. This strain can be employed as
      a powerful workhorse for high-efficient CA recovery from lactate-containing waste
      streams. Our preliminary investigation suggested that the CA production from
      lactate in strain CPB6 might be via the chain elongation pathway of the reverse
      beta-oxidation; the detailed mechanism, however, warrants further investigation
      using various molecular microbiology techniques.

PMID- 28439296
TI  - Oxidation of a non-phenolic lignin model compound by two Irpex lacteus manganese
      peroxidases: evidence for implication of carboxylate and radicals.
AB  - BACKGROUND: Manganese peroxidase is one of the Class II fungal peroxidases that
      are able to oxidize the low redox potential phenolic lignin compounds. For high
      redox potential non-phenolic lignin degradation, mediators such as GSH and
      unsaturated fatty acids are required in the reaction. However, it is not known
      whether carboxylic acids are a mediator for non-phenolic lignin degradation.
      RESULTS: The white rot fungus Irpex lacteus is one of the most potent fungi in
      degradation of lignocellulose and xenobiotics. Two manganese peroxidases (IlMnP1
      and IlMnP2) from I. lacteus CD2 were over-expressed in Escherichia coli and
      successfully refolded from inclusion bodies. Both IlMnP1 and IlMnP2 oxidized the
      phenolic compounds efficiently. Surprisingly, they could degrade veratryl
      alcohol, a non-phenolic lignin compound, in a Mn2+-dependent fashion. Malonate or
      oxalate was found to be also essential in this degradation. The oxidation of non
      phenolic lignin was further confirmed by analysis of the reaction products using
      LC-MS/MS. We proved that Mn2+ and a certain carboxylate are indispensable in
      oxidation and that the radicals generated under this condition, specifically
      superoxide radical, are at least partially involved in lignin oxidative
      degradation. IlMnP1 and IlMnP2 can also efficiently decolorize dyes with
      different structures. CONCLUSIONS: We provide evidence that a carboxylic acid may
      mediate oxidation of non-phenolic lignin through the action of radicals. MnPs,
      but not LiP, VP, or DyP, are predominant peroxidases secreted by some white rot
      fungi such as I. lacteus and the selective lignocellulose degrader Ceriporiopsis
      subvermispora. Our finding will help understand how these fungi can utilize MnPs
      and an excreted organic acid, which is usually a normal metabolite, to
      efficiently degrade the non-phenolic lignin. The unique properties of IlMnP1 and
      IlMnP2 make them good candidates for exploring molecular mechanisms underlying
      non-phenolic lignin compounds oxidation by MnPs and for applications in
      lignocellulose degradation and environmental remediation.

PMID- 28439297
TI  - The influence of day/night cycles on biomass yield and composition of Neochloris
      oleoabundans.
AB  - BACKGROUND: Day/night cycles regulate the circadian clock of organisms to program
      daily activities. Many species of microalgae have a synchronized cell division
      when grown under a day/night cycle, and synchronization might influence biomass
      yield and composition. Therefore, the aim of this study was to study the
      influence of day/night cycle on biomass yield and composition of the green
      microalgae Neochloris oleoabundans. Hence, we compared continuous turbidostat
      cultures grown under continuous light with cultures grown under simulated
      day/night cycles. RESULTS: Under day/night cycles, cultures were synchronized as
      cell division was scheduled in the night, whereas under continuous light cell
      division occurred randomly synchronized cultures were able to use the light 10
      15% more efficiently than non-synchronized cultures. Our results indicate that
      the efficiency of light use varies over the cell cycle and that synchronized cell
      division provides a fitness benefit to microalgae. Biomass composition under
      day/night cycles was similar to continuous light, with the exception of starch
      content. The starch content was higher in cultures under continuous light, most
      likely because the cells never had to respire starch to cover for maintenance
      during dark periods. Day/night cycles were provided in a 'block' (continuous
      light intensity during the light period) and in a 'sine' (using a sine function
      to simulate light intensities from sunrise to sunset). There were no differences
      in biomass yield or composition between these two ways of providing light (in a
      'block' or in a 'sine'). CONCLUSIONS: The biomass yield and composition of N.
      oleoabundans were influenced by day/night cycles. These results are important to
      better understand the relations between research done under continuous light
      conditions and with day/night cycle conditions. Our findings also imply that more
      research should be done under day/night cycles.

PMID- 28439298
TI  - Multi-drug resistant pathogenic bacteria in the gut of young children in
      Bangladesh.
AB  - BACKGROUND: The gut of human harbors diverse commensal microbiota performing an
      array of beneficial role for the hosts. In the present study, the major commensal
      gut bacteria isolated by culturing methods from 15 children of moderate income
      families, aged between 10 and 24 months, were studied for their response to
      different antibiotics, and the molecular basis of drug resistance. RESULTS: Of
      122 bacterial colonies primarily selected from Luria-Bertani agar, bacterial
      genera confirmed by analytical profile index (API) 20E(r) system included
      Escherichia as the predominant (52%) organism, followed by Enterobacter (16%),
      Pseudomonas (12%), Klebsiella (6%), Pantoea (6%), Vibrio (3%), and Citrobacter
      (3%); while Aeromonas and Raoultella were identified as the infrequently
      occurring genera. An estimated 11 and 22% of the E. coli isolates carried
      virulence marker genes stx-2 and eae, respectively. Antimicrobial susceptibility
      assay revealed 78% of the gut bacteria to be multidrug resistant (MDR) with
      highest resistance to erythromycin (96%), followed by ampicillin (63%),
      tetracycline (59%), azithromycin (53%), sulfamethoxazole-trimethoprim (43%),
      cefixime (39%), and ceftriaxone (33%). PCR assay results revealed 56% of the gut
      bacteria to possess gene cassette Class 1 integron; while 8, 17.5 and 6% of the
      strains carried tetracycline resistance-related genes tetA, tetB, and tetD,
      respectively. The macrolide (erythromycin and azithromycin) resistance marker
      genes mphA, ereB, and ermB were found in 28, 3 and 5% of bacterial isolates,
      respectively; while 26, 12, 17, 32, 7, 4 and 3% of the MDR bacterial isolates
      carried the extended spectrum beta-lactamase (ESBL)-related genes e.g., blaTEM,
      blaSHV, blaCMY-9, blaCTX-M1, blaCTX-M2, blaCMY-2 and blaOXA respectively.
      Majority of the MDR gut bacteria harbored large plasmids [e.g., 140 MDa (43%),
      105 MDa (30%), 90 MDa (14%)] carrying invasion and related antibiotic resistance
      marker genes. CONCLUSIONS: Our results suggest gut of young Bangladeshi children
      to be an important reservoir for multi-drug resistant pathogenic bacteria
      carrying ESBL related genes.

PMID- 28439299
TI  - Substance P enhances lactic acid and tyramine production in Enterococcus faecalis
      V583 and promotes its cytotoxic effect on intestinal Caco-2/TC7 cells.
AB  - BACKGROUND: Enterococcus faecalis, generally considered as a saprophytic bowel
      commensal, has recently emerged as an important nosocomial pathogen causing
      severe urinary tract infections, surgical wound infections, bacteremia, and
      bacterial endocarditis. This bacterium is capable of forming biofilms on various
      surfaces and its high level of antibiotic resistance contributes to its
      pathogenicity. The aim of this study was to evaluate the effect on E. faecalis,
      of Substance P (SP), an antimicrobial peptide that is produced in the gut and
      skin. RESULTS: We found that SP did not have antibacterial activity against E.
      faecalis V583 (MIC >1000 ug/ml). Conversely, SP stimulated aggregation,
      hydrophobicity, lactic acid and tyramine production in this bacterium. The
      cytotoxicity and bacterial translocation were also accelerated when E. faecalis
      V583 were pretreated with SP before infection of intestinal Caco-2/TC7 cells.
      CONCLUSION: SP can modulate the physiology of E. faecalis. Extensive studies are
      now needed to screen within the human microbiota which bacteria are responsive to
      host molecules, and to identify their sensors.

PMID- 28439300
TI  - Genetic variants of Helicobacter pylori type IV secretion system components CagL
      and CagI and their association with clinical outcomes.
AB  - BACKGROUND: Helicobacter pylori infection is associated with risk for chronic
      gastritis (CG), gastric ulcer (GU), duodenal ulcer (DU), and gastric cancer (GC).
      The H. pylori Cag type IV secretion system (TFSS) translocates the virulence
      factor cytotoxin-associated gene A protein into host cells and plays an important
      role in initiating gastric carcinogenesis. The CagL and CagI proteins are
      components of the TFSS. The Arg-Gly-Asp (RGD) motif of CagL, and the six most
      distal C-terminal amino acids (Ser-Lys-Ile-Ile-Val-Lys, and Ser-Lys-Val-Ile-Val
      Lys) of CagL and CagI are essential for TFSS adhesion to host cells.
      Additionally, the CagL variant Tyr58Glu59 was previously shown to be associated
      with GC patients. RESULTS: We isolated 43 H. pylori isolates from 17 CG, 8 GU, 8
      DU, and 10 GC patients in Southeast Asia. Total DNAs were extracted and sequenced
      with MiSeq. H. pylori strain ATCC 26695, which was isolated from CG patients, was
      used as a reference. We examined the full sequences of H. pylori cagL and cagI
      using whole-genome sequencing (WGS), and analyzed whether single nucleotide
      variants and amino acid changes (AACs) correlated with adverse clinical outcomes.
      Three isolates were excluded from the analysis due to cagPAI rearrangements. CagL
      RGD motifs were conserved in 39 isolates (97.5%). CagL-Glu59 and Ile234 in the C
      terminal motif were more common in 10 H. pylori isolates from GC patients (p <
      0.001 and p < 0.05, respectively). When 5 Vietnamese isolates from GC patients
      were excluded, CagL-Glu59 still remains significant (p < 0.05), but not Ile234.
      CagL-Tyr58 was seen in only one isolate. The CagI C-terminal motif was completely
      conserved across all 40 isolates, and there were no significant AACs in CagI.
      CONCLUSIONS: Using WGS, we analyzed genetic variants in clinical H. pylori
      isolates and identified putative novel and candidate variants in uncharacterized
      CagL and CagI sequences that are related to gastric carcinogenesis. In
      particular, CagL-Glu59 has the possible association with GC.

PMID- 28439302
TI  - Femoral osteochondritis of the knee: prognostic value of the mechanical axis.
AB  - PURPOSE: Femoral osteochondritis dissecans (OCD) is a disorder of unknown
      aetiology and variable prognosis that causes knee pain. In this paper, the
      authors study the impact of lower limb malalignment on the development and
      prognosis of OCD. METHODS: After anteroposterior (AP) and lateral radiograph and
      MRI of the knee, 53 cases of OCD were diagnosed. All patients were studied by
      standing full-length AP radiograph of the lower extremities in order to analyse
      the relationship between the femorotibial and mechanical axis and the location
      and stability of the osteochondritis. RESULTS: The OCD lesion was located in the
      medial condyle (zone 2) in 75.5% of cases (40 cases). The lateral condyle was
      affected in 24.5% of cases (zone 4 in nine cases and zone 5 in four cases). The
      femorotibial angle (anatomical axis) was normally aligned in 68% of cases. A
      valgus deformity was observed in 9.5% of cases and a varus deformity in 22.5%.
      The mechanical axis of the limb appeared normal in only 32% of cases, with medial
      deviation in 53%, and lateral deviation in 15% of cases. When the OCD lesion was
      located in the medial condyle (40 cases), the mechanical axis also crossed the
      knee through the medial zone in 28 cases. When the OCD lesion was located in the
      lateral condyle (13 cases), the mechanical axis crossed the knee through zones 1
      or 2 in four cases. In stable OCD, the mechanical axis and location of the lesion
      coincided in 19 of 36 cases (52%), compared with 16 of 17 cases (94%) in unstable
      OCD. CONCLUSIONS: There is a high correlation between OCD location and lower limb
      mechanical axis deviation. The convergence of the mechanical axis with the
      location of the OCD lesion may be considered an associated factor in fragment
      instability. This convergence is more common in unstable OCD.

PMID- 28439301
TI  - Prevalence, virulence potential, and pulsed-field gel electrophoresis profiling
      of Shiga toxin-producing Escherichia coli strains from cattle.
AB  - BACKGROUND: As a primary source of Shiga-toxin-producing Escherichia coli (STEC)
      infection, cattle are often targeted to develop strategies for reducing STEC
      contamination. Monitoring the virulence potentials of STEC isolates from cattle
      is important for tracing contamination sources, managing outbreaks or sporadic
      cases, and reducing the risks for human infection. This study aimed to
      investigate the prevalence of STEC in cattle farm samples in South Korea and to
      assess their virulence potentials. RESULTS: In total, 63 STEC were isolated from
      496 cattle farm samples, and temperature and rainfall affected STEC prevalence (p
      < 0.001). The O157 serogroup was most prevalent, followed by O108, O8, O84, O15,
      and O119. In the stx variant test, high prevalence of stx2a and stx2c (known to
      be associated with high STEC virulence) were observed, and stx2g, a bovine STEC
      variant, was detected in STEC O15 and O109. Additionally, stx1c was detected in
      eae-positive STEC, suggesting genetic dynamics among the virulence genes in the
      STEC isolates. STEC non-O157 strains were resistant to tetracycline (17.9%),
      ampicillin (14.3%), and cefotaxime (3.6%), while STEC O157 was susceptible to all
      tested antimicrobials, except cefotaxime. The antimicrobial resistance genes,
      blaTEM (17.5%), tetB (6.3%), and tetC (4.8%), were only detected in STEC non
      O157, whereas tetE (54.0%) was detected in STEC O157. AmpC was detected in all
      STEC isolates. Clustering was performed based on the virulence gene profiles,
      which grouped STEC O84, O108, O111, and O157 together as potentially pathogenic
      STEC strains. Finally, PFGE suggested the presence of a prototype STEC that
      continues to evolve by genetic mutation and causes within- and between-farm
      transmission within the Gyeonggi province. CONCLUSIONS: Considerable numbers of
      STEC non-O157 were isolated from cattle farms, and the virulence and
      antimicrobial resistance features were different between the STEC O157 and non
      O157 strains. STEC from cattle with virulence or antimicrobial resistance genes
      might represent a threat to public health and therefore, continual surveillance
      of both STEC O157 and non-O157 would be beneficial for controlling and preventing
      STEC-related illness.

PMID- 28439303
TI  - Proximal femoral osteotomy in children with cerebral palsy: the perspective of
      the trainee.
AB  - BACKGROUND: There are a range of implants for fixation of proximal femoral
      osteotomies (PFOs) in children. We investigated the training experiences and
      preferences of orthopaedic residents and fellows who were learning PFO, using a
      fixed angled blade plate (ABP) or a locking, cannulated blade plate (LCBP). We
      also studied short-term technical and radiographic outcomes. METHODS: This was a
      prospective, parallel-group, cohort study of 90 consecutive children and
      adolescents with cerebral palsy who underwent bilateral PFOs with ABP or LCBP.
      Surgical trainees completed a questionnaire to document the ease or difficulty of
      each operative step. RESULTS: There were 48 boys and 42 girls, with a mean age of
      eight years and a mean follow-up of 25 months. Trainees preferred the LCBP system
      for: insertion of the guidewire, the seating chisel and the blade plate, as well
      as overall technical ease of use (p < 0.001). Radiographic outcomes were similar
      with no between-group differences for migration percentage (p = 0.996) or neck
      shaft angle (p = 0.849), but there was a higher prevalence of technical errors in
      the ABP group. CONCLUSIONS: Trainee surgeons expressed a preference for LCBPs
      when learning PFO in children with cerebral palsy. Radiographic outcomes were
      similar in both groups, with close attending surgeon supervision.

PMID- 28439304
TI  - Is percutaneous medial hamstring myofascial lengthening as anatomically effective
      and safe as the open procedure?
AB  - BACKGROUND: Medial hamstring fractional lengthening is commonly performed in
      children with cerebral palsy (CP) to decrease contracture and/or to improve gait.
      Percutaneous procedures are gaining more and more popularity, even in the
      paediatric population, with equivocal results. The purpose of this paper was to
      determine the efficacy and safety of percutaneous medial hamstring myofascial
      lengthening (PHL). METHODS: This is a prospective randomised controlled trial
      including 31 knees from 18 consecutive patients with CP scheduled for medial
      hamstring lengthening in the setting of multilevel tendon lengthening procedures
      in a university hospital. Other concomitant lower extremity surgeries were not
      exclusionary. A first paediatric orthopaedic surgeon executes the PHL at one
      level, as recently described in the literature. Another surgeon opens and extends
      the wound to explore what had been cut during the PHL and completes fractional
      lengthening (OHL) of both the semimembranosus (SM) and semitendinosus (ST) when
      possible. Popliteal angle (PA) was assessed by a third surgeon immediately before
      PHL, after PHL and then after OHL, using a goniometer in a standardised
      reproducible manner. All three surgeons were blinded to the others' findings.
      Primary endpoints included ease of performing PHL, the percentage of tendon
      fascia/ muscle portion sectioned percutaneously and improvement of PA. Comparison
      between improvement of PA after PHL and OHL was done using a paired t-test with a
      95% confidence interval. RESULTS: The first surgeon was at ease in palpating and
      identifying the semimembranosus tendon before PHL in ten knees only. PHL led to
      an undesirable cut of the semimembranosus muscle fibres to more than 50% of the
      muscle section area in eight cases (<50% in 23 cases, between 50% and 75% in
      eight cases), and of the semitendinosus muscle fibres to more than 50% in all
      cases (complete rupture in six cases, more than 75% in eight cases and
      approximately 50% in 17 cases). Mean PA measured 52 degrees  pre-operatively and
      decreased to 40 degrees  after PHL. After OHL, the PA averaged 22 degrees . There
      was a significant difference between the PA value after PHL (M = 40, SD = 11.8)
      and the PA value after OHL (M = 22, SD = 8.7), p < 0.0001. The gain in PA did not
      correlate with the extent of semimembranosus muscle divided (p = 0.38) nor with
      the extent of semitendinosus muscle divided (p = 0.35). No major iatrogenic
      neurovascular injury was observed. CONCLUSIONS: To the authors' knowledge, this
      is the first prospective study concerning the anatomic effects of PHL. Although
      it is a quick procedure, it is often associated with difficulty by the operating
      surgeon to identify and evaluate what should be cut percutaneously, leading to
      abusive injury of the muscle itself rather than the fascia alone. In addition,
      the gain in PA is statistically less following PHL than following OHL despite
      undesirable extensive muscle injury following PHL. This may be due to the
      multiple fascial cuts (fractional lengthening) usually performed in OHL.

PMID- 28439305
TI  - Costal cartilage transplantation for treatment of growth plate injury in a rabbit
      model.
AB  - OBJECTIVES: The purpose of this study is to evaluate the effects of allogenic
      costal cartilage transplantation on preventing bony bridge formation and angular
      deformities for the treatment of partial growth plate injury using a rabbit
      model. METHODS: An experimental model of partial growth injury was created by
      resecting the medial part of the proximal tibial growth plate in male six-week
      old New Zealand White rabbits. The rabbits were divided into four groups: no
      surgery; no transplantation; bone wax transplantation; and allogenic costal
      cartilage transplantation. The angular deformities of the tibia and bony bridge
      were analysed using radiographs and microcomputed tomography, and the repair of
      the injured growth plate cartilage and bony bridge formation rate were
      histologically evaluated. RESULTS: On radiographic evaluation, the varus
      deformities in the costal cartilage group were significantly improved compared
      with the no transplantation group at four and eight weeks after operation and
      with the bone wax group at eight weeks after operation. Micro-computed tomography
      showed that the bony bridge formation was prevented in the bone wax and costal
      cartilage groups. Histological findings showed that the bony bridge formation in
      the bone wax and costal cartilage group was decreased. In addition, the growth
      plate was continuous and stained with safranin O and immunohistochemically
      stained for type II collagen. CONCLUSION: Transplantation of costal cartilage
      improved angular deformities and decreased bony bridge formation in the partial
      growth plate injury. Costal cartilage might be a suitable graft for the treatment
      of growth plate injury.

PMID- 28439306
TI  - Fibular strut graft for nonunited femoral neck fractures in children.
AB  - PURPOSE: To evaluate the clinical and radiological outcomes of using fibular
      strut grafts as a fixation device for non-united femoral neck fractures in
      children with or without subtrochanteric valgus osteotomy. METHODS: A total of 12
      children with non-united femoral neck fractures (nine males and three females)
      with an average age of 8.2 years (5 to 12) were managed, and functional results
      evaluated, between July 2013 and July 2015. The mechanisms of injury were fall
      from a height in ten patients and road traffic accident in two cases. Nine cases
      of femoral neck nonunion followed failed internal fixation and three cases were
      neglected fractures. Six cases were treated by fibular strut graft and
      subtrochanteric valgus osteotomy with contoured plate and six cases were treated
      by fibular strut graft and hip spica. RESULTS: The mean follow-up period was 20.4
      months (12 to 36). Union was achieved in all 12 cases by a mean of 3.5 months
      (2.5 to 6). All patients were satisfied at five months. For final analysis of
      clinical and radiographic results, the Ratliff's classification was used. We
      classed 11 cases as good results and one case as fair. CONCLUSIONS: Fibular strut
      grafts are a reliable option for treatment of pseudo-arthrosis in femoral neck
      fracture nonunion in children. It is successful in restoration of femoral neck
      length in children with non-united femoral neck fractures.

PMID- 28439307
TI  - Fluoroscopic imaging overestimates the screw tip to subchondral bone distance in
      a cadaveric model of slipped capital femoral epiphysis.
AB  - PURPOSE: Intra-operative imaging plays a key role in screw placement for slipped
      capital femoral epiphysis (SCFE). Complications have been associated with
      inadequate screw position. The purpose of this study was to evaluate computed
      tomography (CT) (3D fluoroscopy) and standard fluoroscopy (C-arm) images as
      compared with direct anatomic measurement to determine final screw position in a
      cadaveric SCFE model. METHODS: Osteotomy with pinning was performed at the
      physeal scar in ten cadaveric hips. A standardised approach-withdrawal technique
      was performed with C-arm images taken at 15 degrees  increments. We also obtained
      a CT (3D fluoroscopy) scan of each hip. The screw tip-subchondral bone (STSB)
      distance was measured on digital imaging software and also with a digital
      calliper directly when the femoral head was cut in plane to expose the STSB
      distance anatomically. Statistical analysis included t-tests and Fisher's exact
      test. RESULTS: Moderate SCFE osteotomies were achieved with a mean Southwick
      angle (39.5 degrees  +/- 7 degrees ). The 60 degrees  fluoroscopic image was
      found to be the most representative image (41% of the time) compared with both
      anteroposterior (AP) and lateral images (8% and 21%). Both fluoroscopy (2.7 +/-
      0.8 mm, p < 0.001) and CT (1.6 +/- 0.7 mm, p = 0.03) overestimated the STSB
      distance compared with direct measurement (0.94 +/-  0.51 mm). Two-thirds (67%)
      of CT measurements were within 1 mm of the cadaveric measurement, while only 20%
      of C-arm measurements fulfilled this criterion (p = 0.04). CONCLUSIONS: Both
      standard fluoroscopy and CT overestimated the STSB distance when compared with
      direct measurement in a cadaveric model of SCFE. Surgeons should be aware of the
      limitations of intra-operative imaging to determine the STSB distance. We suggest
      that using the known pitch of a screw (2.9 mm in a 7.3-mm cannulated screw) as an
      intra-operative tool to help guide screw placement.

PMID- 28439308
TI  - Vertical expandable prosthetic titanium ribs (VEPTR) in early-onset scoliosis:
      impact on thoracic compliance and sagittal balance.
AB  - BACKGROUND: Theoretically, dynamic thoracic compliance (DTC) should be reduced by
      vertical expandable prosthetic titanium ribs (VEPTR) since titanium rods, scar
      tissue and ossifications increase stiffness of the rib cage. The effect of VEPTR
      on thoracic compliance has not yet been elucidated. The impact of VEPTR on the
      development of sagittal balance has not been fully investigated. PATIENTS AND
      METHODS: In a retrospective study, we investigated 21 consecutive children who
      were treated by VEPTR from 2004 to 2011 and three control groups. We compared the
      development of thoracic compliance during growth to Nr1. Development of sagittal
      balance during growth was compared to Nr2 and to Nr3 (which has been instrumented
      from ileum to rib). Mean follow-up was 60.67 months (standard error of the mean
      (SE 4.77). RESULTS: The difference of change of DTC during growth of VEPTR group
      versus a control group was not significant (p < 0.05). However, initial DTC and
      DTC at last follow-up of VEPTR group were lower than DTC of the control group.
      The difference was significant (p < 0.05). Mean correction of Cobb angle after
      the first operation was 16.41 degrees  (SE 3.01). Until last follow-up, we saw a
      loss of correction of 8.23 degrees  (SE 3.22). The differences between the
      development of parameters of sagittal balance during growth between the VEPTR
      group, control group 2 and control group 3 were not significant (p > 0.05).
      CONCLUSIONS: VEPTR treatment should start as early as possible since VEPTR seems
      to lead to an increased rate of DTC that is similar to healthy controls. Sagittal
      balance showed a similar development as in healthy children.

PMID- 28439309
TI  - Paediatric pelvic fractures: how do they differ from adults?
AB  - BACKGROUND: The aim of this article was to review the incidence, presentation,
      treatment and complications of paediatric pelvic fractures of children who were
      admitted to our level 1 trauma centre and to compare them with our data from
      adult pelvic fracture patients. METHODS: We conducted a retrospective chart
      review of all children with pelvic fractures who were managed at our institution
      between January 1993 and December 2013 and compared the data with our database on
      pelvic fractures in adults during the period 2007 to 2012. RESULTS: We identified
      51 children and 268 adults with pelvic fractures. The median age of the
      paediatric patients was 11 years. Children were significantly more involved in
      traffic accidents than adults (p < 0.001). Adults had a significantly higher
      Injury Severity Score (ISS) (31 vs 24.5; p < 0.03) and were significantly more
      often haemodynamically unstable (p < 0.01). Adults had a type C fracture more
      often, while children had a type B fracture (p < 0.001). Associated injuries were
      seen in both groups; however, thoracic injuries were significantly higher in
      adults (p < 0.01) and injuries to the extremities were higher in children (p <
      0.01). Adults were significantly more often treated with open reduction and
      internal fixation (p < 0.001). Mortality in both groups, however, did not differ
      (6% vs 8%). CONCLUSION: Paediatric pelvic fractures are rare. They differ from
      adult pelvic fractures in presentation, associated injuries and management.
      Mortality, however, is substantial and does not differ from the adult population.
      Mortality is often due to concomitant injuries and not to exsanguination from the
      pelvic fracture.

PMID- 28439310
TI  - Syndesmosis injuries in the pediatric and adolescent athlete: an analysis of risk
      factors related to operative intervention.
AB  - PURPOSE: To review all paediatric ankle syndesmotic injuries occurring at our
      institution and identify risk factors associated with operative intervention.
      METHODS: Among 22 873 evaluations for ankle trauma, we found 220 children
      suffering from syndesmotic injuries (incidence: 0.96%). We recorded demographic
      data, details of the injury, features on examination and treatment variables.
      Univariable and multivariable logistic regression modelling was performed to
      identify risk factors associated with operative intervention. RESULTS: The mean
      age at injury was 15.8 years (8.9 to 19.0) with a median follow-up of 13 weeks
      (IQR 5 to 30 weeks). A sports-related injury was most common (168/220, 76%). A
      total of 82 of 220 (37%) patients underwent operative fixation, of which 76 (93%)
      had an associated fibular fracture. Patients undergoing surgery had a higher
      incidence of swelling and inability to weight bear (p < 0.001). Statistically
      significant differences were recorded in tibiofibular (TF) clear space, TF
      overlap and medial clear space (MCS) between the operative and non-operative
      cohorts (6.0 vs 4.6 mm (p = 0.002), 5.4 vs 6.9 mm (p = 0.004) and 6.4 vs 3.5 mm
      (p < 0.001)). Multivariable analysis revealed patients with a fracture of the
      ankle had 44 times the odds of surgical intervention, patients with a closed
      physis had over five times the odds of surgical intervention and patients with a
      medial clear space greater than 5 mm had nearly eight times the odds of requiring
      surgical intervention. CONCLUSIONS: Operative ankle syndesmotic injuries in the
      paediatric population are often associated with a closed distal tibial physis and
      concomitant fibular fracture.

PMID- 28439311
TI  - Treatment of shepherd's crook deformity in patients with polyostotic fibrous
      dysplasia using a new type of custom made retrograde intramedullary nail: a
      technical note.
AB  - AIMS: The severe form of coxa vara, the 'shepherd's crook deformity', is always a
      consequence of a locally extensive form of polyostotic fibrous dysplasia (or
      McCune-Albright syndrome). Treatment of this deformity is a challenge. The soft
      bone does not tolerate any implant that depends on the stability of the cortical
      bone (like plates or external fixators). Intramedullary nails are the most
      appropriate implants for stabilisation, but if they are inserted from the greater
      trochanter, they cannot correct the varus deformity enough. PATIENTS AND METHODS:
      We have developed a special intramedullary nail that can be inserted from the
      osteotomy site and can be driven retrograde into the femoral neck in an
      appropriate valgus position. We have operated 15 legs in 13 patients. The average
      age at surgery was 14 years and 5 months (6 to 28.9). In all, 11 femora had been
      operated before (unsuccessfully) with various implants. RESULTS: The average
      follow-up was 54.2 months (7 to 132). The average correction of the neck/(distal)
      shaft angle was 57.5 degrees  (10 degrees  to 80 degrees ) ( = 72.8%). While pre
      operatively none of the patients was able to walk without aid, at follow-up only
      one patient was unable to walk, three used the aid of crutches because of tibial
      lesions and one patient had an increased external rotation of the leg. At follow
      up, most patients were free of pain. One implant broke and had to be replaced.
      CONCLUSION: This new operative method offers the possibility of efficient
      correction and stabilisation of this severe and difficult deformation.

PMID- 28439312
TI  - Validation of the multiplier method for leg-length predictions on a large
      European cohort and an assessment of the effect of physiological age on
      predictions.
AB  - PURPOSE: The Avon Longitudinal Study of Parents and Children (ALSPAC) prospective
      cohort was used to determine the accuracy of the Paley multiplier method for
      predicting leg length. Using menarche as a proxy, physiological age was then used
      to increase the accuracy of the multiplier. METHODS: Chronological age was
      corrected in female patients over the age of eight years with documented date of
      first menses. Final sub-ischial leg length and predicted final leg length were
      predicted for all data points. RESULTS: Good correlation was demonstrated between
      the Paley and ALSPAC data. The average error in prediction depended on the time
      of assessment, tending to improve as the child got older. It varied from 2.2 cm
      at the age of seven years to 1.8 cm at the age of 14 years. When chronological
      age was corrected, the accuracy of multiplier increased. Age correction of 50%
      improved multiplier predictions by up to 28%. CONCLUSION: There appears to have
      been no significant change in growth trajectories of the two populations who were
      chronologically separated by 40 years. While the Paley data were based on
      extracting trends from averaged data, the ALSPAC dataset provides descriptive
      statistics from which it is possible to compare populations and assess the
      accuracy of the multiplier method. The data suggest that the accuracy improves as
      the patient gets close to the average skeletal maturity but that results need to
      be interpreted in conjunction with a radiological assessment of the growth
      plates. The magnitude of the errors in prediction suggest that when using the
      multiplier, the clinician must remain vigilant and prepared to perform a
      contralateral epiphyseodisis if the prediction proves to be wrong. The data
      suggest a relationship between the multiplier and menarche. There appears to be a
      factorisation and when accounting for physiological age, one needs to correct by
      50% of the difference between chronological and physiological age.

PMID- 28439313
TI  - PER ASPERA AD ASTRA: through hardships to the stars.

PMID- 28439314
TI  - Correction of lower limb deformities in children with renal osteodystrophy by
      guided growth technique.
AB  - PURPOSE: Renal osteodystrophy (ROD) may cause severe lower limb deformities in
      children. The purpose of this study is to evaluate the efficacy of the temporary
      hemiepiphysiodesis for the correction of lower limb deformities in children with
      ROD. METHODS: Guided growth correction by hemiepiphysiodesis has been performed
      in skeletally immature patients with deformities of the lower limbs caused by
      ROD. The correction of the mechanical axes of the lower limbs and its correction
      speed have been evaluated. RESULTS: A total of seven patients with ROD, five
      males and two females, were treated with the above technique. The average age of
      the patients at their first surgery was 7.8 years (2.9 to 13.6). The average
      follow-up time 5.2 years (2.3 to 8). There were 13 valgus deformities and one
      varus deformity of the knee. The measure of the lower limb angular deformity was
      in the range of 10 degrees  to 47 degrees . Restoration of normal mechanical axis
      was achieved in all patients at the final follow-up. Three patients relapsed and
      required further hemiepiphysiodesis. The average time for correction was 20
      months (7 to 30). The average speed of correction was 0.49 degrees  per month for
      a tibia and 1.73 degrees  per month for a femur. There were two minor
      complications: a screw mobilisation and a screw breakage occurred during removal.
      CONCLUSION: Guided growth technique by hemiepiphysiodesis is a mini-invasive
      surgical procedure that has been found to be effective for the correction of
      misalignment due to ROD in skeletally immature patients. The method has allowed
      progressive correction of the deformities at any age in childhood. These patients
      are predisposed to relapse to their deformities, thus a strict follow-up is
      required.

PMID- 28439315
TI  - 36 h fasting of young men influences adipose tissue DNA methylation of LEP and
      ADIPOQ in a birth weight-dependent manner.
AB  - BACKGROUND: Subjects born with low birth weight (LBW) display a more energy
      conserving response to fasting compared with normal birth weight (NBW) subjects.
      However, the molecular mechanisms explaining these metabolic differences remain
      unknown. Environmental influences may dynamically affect epigenetic marks, also
      in postnatal life. Here, we aimed to study the effects of short-term fasting on
      leptin (LEP) and adiponectin (ADIPOQ) DNA methylation and gene expression in
      subcutaneous adipose tissue (SAT) from subjects with LBW and NBW. METHODS: Twenty
      one young LBW men and 18 matched NBW controls were studied during 36 h fasting.
      Eight subjects from each group completed a control study (overnight fast). We
      analyzed SAT LEP and ADIPOQ methylation (Epityper MassARRAY), gene expression (q
      PCR), and adipokine plasma levels. RESULTS: After overnight fast (control study),
      LEP and ADIPOQ DNA methylation levels were higher in LBW compared to those in NBW
      subjects (p <= 0.03) and increased with 36 h fasting in NBW subjects only (p <=
      0.06). Both LEP and ADIPOQ methylation levels were positively associated with
      total body fat percentage (p <= 0.05). Plasma leptin levels were higher in LBW
      versus NBW subjects after overnight fasting (p = 0.04) and decreased more than
      threefold in both groups after 36 h fasting (p <= 0.0001). CONCLUSIONS: This is
      the first study to demonstrate that fasting induces changes in DNA methylation.
      This was shown in LEP and ADIPOQ promoters in SAT among NBW but not LBW subjects.
      The altered epigenetic flexibility in LBW subjects might contribute to their
      differential response to fasting, adipokine levels, and increased risk of
      metabolic disease.

PMID- 28439318
TI  - Bodily Effort Enhances Learning and Metacognition: Investigating the Relation
      Between Physical Effort and Cognition Using Dual-Process Models of Embodiment.
AB  - Recent embodiment research revealed that cognitive processes can be influenced by
      bodily cues. Some of these cues were found to elicit disparate effects on
      cognition. For instance, weight sensations can inhibit problem-solving
      performance, but were shown to increase judgments regarding recall probability
      (judgments of learning; JOLs) in memory tasks. We investigated the effects of
      physical effort on learning and metacognition by conducting two studies in which
      we varied whether a backpack was worn or not while 20 nouns were to be learned.
      Participants entered a JOL for each word and completed a recall test. Experiment
      1 (N = 18) revealed that exerting physical effort by wearing a backpack led to
      higher JOLs for easy nouns, without a notable effect on difficult nouns.
      Participants who wore a backpack reached higher recall scores. Therefore,
      physical effort may act as a form of desirable difficulty during learning. In
      Experiment 2 (N = 30), the influence of physical effort on JOL s and learning
      disappeared when more difficult nouns were to be learned, implying that a high
      cognitive load may diminish bodily effects. These findings suggest that physical
      effort mainly influences superficial modes of thought and raise doubts concerning
      the explanatory power of metaphor-centered accounts of embodiment for higher
      level cognition.

PMID- 28439319
TI  - Mechanisms of Practice-Related Reductions of Dual-Task Interference with Simple
      Tasks: Data and Theory.
AB  - In dual-task situations, interference between two simultaneous tasks impairs
      performance. With practice, however, this impairment can be reduced. To identify
      mechanisms leading to a practice-related improvement in sensorimotor dual tasks,
      the present review applied the following general hypothesis: Sources that impair
      dual-task performance at the beginning of practice are associated with mechanisms
      for the reduction of dual-task impairment at the end of practice. The following
      types of processes provide sources for the occurrence of this impairment: (a)
      capacity-limited processes within the component tasks, such as response-selection
      or motor response stages, and (b) cognitive control processes independent of
      these tasks and thus operating outside of component-task performance. Dual-task
      practice studies show that, under very specific conditions, capacity-limited
      processes within the component tasks are automatized with practice, reducing the
      interference between two simultaneous tasks. Further, there is evidence that
      response-selection stages are shortened with practice. Thus, capacity limitations
      at these stages are sources for dual-task costs at the beginning of practice and
      are overcome with practice. However, there is no evidence demonstrating the
      existence of practice-related mechanisms associated with capacity-limited motor
      response stages. Further, during practice, there is an acquisition of executive
      control skills for an improved allocation of limited attention resources to two
      tasks as well as some evidence supporting the assumption of improved task
      coordination. These latter mechanisms are associated with sources of dual-task
      interference operating outside of component task performance at the beginning of
      practice and also contribute to the reduction of dual-task interference at its
      end.

PMID- 28439320
TI  - Distractor-Induced Blindness: A Special Case of Contingent Attentional Capture?
AB  - The detection of a salient visual target embedded in a rapid serial visual
      presentation (RSVP) can be severely affected if target-like distractors are
      presented previously. This phenomenon, known as distractor-induced blindness
      (DIB), shares the prerequisites of contingent attentional capture (Folk,
      Remington, & Johnston, 1992). In both, target processing is transiently impaired
      by the presentation of distractors defined by similar features. In the present
      study, we investigated whether the speeded response to a target in the DIB
      paradigm can be described in terms of a contingent attentional capture process.
      In the first experiments, multiple distractors were embedded in the RSVP stream.
      Distractors either shared the target's visual features (Experiment 1A) or
      differed from them (Experiment 1B). Congruent with hypotheses drawn from
      contingent attentional capture theory, response times (RTs) were exclusively
      impaired in conditions with target-like distractors. However, RTs were not
      impaired if only one single target-like distractor was presented (Experiment 2).
      If attentional capture directly contributed to DIB, the single distractor should
      be sufficient to impair target processing. In conclusion, DIB is not due to
      contingent attentional capture, but may rely on a central suppression process
      triggered by multiple distractors.

PMID- 28439321
TI  - Embolization of a Bronchial Artery Aneurysm in a Chronic Obstructive Pulmonary
      Disease (COPD) Patient with Non-Massive Hemoptysis.
AB  - BACKGROUND: Bronchial artery aneurysm (BAA) is a rare condition with a reported
      prevalence of less than 1% of all selective bronchial arterial angiograms.
      Despite its low incidence, BAA represents a potential cause of hemoptysis. CASE
      REPORT: We describe the case of a 63-year-old man suffering from chronic
      obstructive pulmonary disease (COPD), who presented with non-massive hemoptysis.
      CT angiography revealed a single bronchial artery aneurysm of 9 mm in diameter,
      abutting the esophageal wall. Other CT findings included hypertrophy of the
      bronchial arteries along the mediastinal course, diffuse thickening of the walls
      of numerous bronchial branches and a "ground glass" opacity in the anterior
      segment of the right upper pulmonary lobe suggestive of alveolar hemorrhage. The
      final diagnosis was established based on selective angiography, which was
      followed by transcatheter arterial embolization (TAE) of the BAA and of the
      pathological bronchial circulation. Follow-up CT scans revealed a total exclusion
      of the aneurysm from the systemic circulation, resolution of the parenchymal
      "ground glass" opacity and absence of further episodes of hemoptysis over a
      period of two years. CONCLUSIONS: An incidental finding of a bronchial artery
      aneurysm necessitates prompt treatment. CT angiography and TAE represent the
      methods of choice for an appropriate diagnosis and treatment, respectively. In
      case of a BAA associated with chronic inflammatory diseases, such as COPD, in
      patients with hemoptysis, TAE of the BAA and of the pathological bronchial
      circulation, in association with the treatment of the underlying disease,
      represents a valid approach that can improve the pulmonary status and prevent
      further episodes of hemoptysis.

PMID- 28439316
TI  - Epigenetic assays for chemical biology and drug discovery.
AB  - The implication of epigenetic abnormalities in many diseases and the approval of
      a number of compounds that modulate specific epigenetic targets in a
      therapeutically relevant manner in cancer specifically confirms that some of
      these targets are druggable by small molecules. Furthermore, a number of
      compounds are currently in clinical trials for other diseases including
      cardiovascular, neurological and metabolic disorders. Despite these advances, the
      approved treatments for cancer only extend progression-free survival for a
      relatively short time and being associated with significant side effects. The
      current clinical trials involving the next generation of epigenetic drugs may
      address the disadvantages of the currently approved epigenetic drugs. The
      identification of chemical starting points of many drugs often makes use of
      screening in vitro assays against libraries of synthetic or natural products.
      These assays can be biochemical (using purified protein) or cell-based (using for
      example, genetically modified, cancer cell lines or primary cells) and performed
      in microtiter plates, thus enabling a large number of samples to be tested. A
      considerable number of such assays are available to monitor epigenetic target
      activity, and this review provides an overview of drug discovery and chemical
      biology and describes assays that monitor activities of histone deacetylase,
      lysine-specific demethylase, histone methyltransferase, histone acetyltransferase
      and bromodomain. It is of critical importance that an appropriate assay is
      developed and comprehensively validated for a given drug target prior to
      screening in order to improve the probability of the compound progressing in the
      drug discovery value chain.

PMID- 28439322
TI  - Susceptibility Imaging in Glial Tumor Grading; Using 3 Tesla Magnetic Resonance
      (MR) System and 32 Channel Head Coil.
AB  - BACKGROUND: Susceptibility weighted imaging (SWI) is a velocity compensated, high
      resolution three-dimensional (3D) spoiled gradient-echo sequence that uses
      magnitude and filtered-phase data. SWI seems to be a valuable tool for non
      invasive evaluation of central nervous system gliomas. Relative cerebral blood
      volume (rCBV) ratio is one of the best noninvasive methods for glioma grading.
      Degree of intratumoral susceptibility signal (ITSS) on SWI correlates with rCBV
      ratio and histopathological grade. This study investigated the effectiveness of
      ITSS grading and rCBV ratio in preoperative assessment. MATERIAL/METHODS: Thirty
      one patients (17 males and 14 females) with histopathogical diagnosis of glial
      tumor undergoing routine cranial MRI, SWI, and perfusion MRI examinations between
      October 2011 and July 2013 were retrospectively enrolled. All examinations were
      performed using 3T apparatus with 32-channel head coil. We used ITSS number for
      SWI grading. Correlations between SWI grade, rCBV ratio, and pathological grading
      were evaluated. ROC analysis was performed to determine the optimal rCBV ratio to
      distinguish between high-grade and low-grade glial tumors. RESULTS: There was a
      strong positive correlation between both pathological and SWI grading. We
      determined the optimal rCBV ratio to discriminate between high-grade and low
      grade tumors to be 2.21. CONSLUSIONS: In conclusion, perfusion MRI and SWI using
      3T MR and 32-channel head coil may provide useful information for preoperative
      glial tumor grading. SWI can be used as an accessory to perfusion MR technique in
      preoperative tumor grading.

PMID- 28439323
TI  - Caudal Regression Syndrome: A Case Series of a Rare Congenital Anomaly.
AB  - BACKGROUND: Caudal regression syndrome is a rare, neural tube defect
      characterized by an abnormal development of the caudal aspect of the vertebral
      column and the spinal cord., It results in neurological deficits ranging from
      bladder and bowel involvement to severe sensory and motor deficits in the lower
      limbs. Maternal diabetes, genetic factors and some teratogens have been shown to
      be associated with its pathogenesis. Caudal regression syndrome is usually
      diagnosed initially by antenatal ultrasound with more definitive diagnosis made
      by antenatal or postnatal MRI. In this case series, we report four cases of
      caudal regression syndrome in different age groups including prenatal, infant and
      adult. CASE REPORT: We are presenting multimodal imaging findings of 4 cases of
      caudal regression syndrome in 4 different age groups including fetus, infant,
      early childhood and adult. The pathogenesis, associated risk factors,
      complications, treatment options and prognosis of caudal regression syndrome are
      discussed as well. CONCLUSIONS: Caudal regression syndrome is a rare entity,
      characterized by sacrococcygeal dysgenesis with an abrupt termination of a blunt
      ending spinal cord. Ultrasound and fetal MRI can be used to make a prenatal
      diagnosis, while MRI is the imaging modality of choice in adults. Early detection
      and prompt treatment is very important to decrease the risk of complications, and
      thus, to improve the prognosis.

PMID- 28439324
TI  - Contemporary Diagnostic Imaging of Oral Squamous Cell Carcinoma - A Review of
      Literature.
AB  - Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity
      and constitutes 95% of all cancers of this area. Men are affected twice as
      commonly as women, primarily if they are over 50 years of age. Forty percent of
      the lesions are localized in the tongue and 30% in the floor of the oral cavity.
      OSCC often affects upper and lower gingiva, buccal mucous membrane, the
      retromolar triangle and the palate. The prognosis is poor and the five-year
      survival rate ranges from 20% (OSCC in the floor of the mouth) to 60% (OSCC in
      the alveolar part of the mandible). Treatment is difficult, because of the
      localization and the invasiveness of the available methods. The diagnosis is made
      based on a histopathological examination of a biopsy sample. The low detection
      rate of early oral SCC is a considerable clinical issue. Although the oral cavity
      can be easily examined, in the majority of cases oral SCC is diagnosed in its
      late stages. It is difficult to diagnose metastases in local lymph nodes and
      distant organs, which is important for planning the scope of resection and
      further treatment, graft implantation, and differentiation between reactive and
      metastatic lymph nodes as well as between disease recurrence and scars or adverse
      reactions after surgery or radiation therapy. Imaging studies are performed as
      part of the routine work-up in oral SCC. However, it is difficult to interpret
      the results at the early stages of the disease. The following imaging methods are
      used - dental radiographs, panoramic radiographs, magnetic resonance imaging with
      diffusion-weighted and dynamic sequences, perfusion computed tomography, cone
      beam computed tomography, single-photon emission computed tomography, hybrid
      methods (PET/CT, PET/MRI, SPECT/CT) and ultrasound. Some important clinical
      problems can be resolved with the use of novel modalities such as MRI with ADC
      sequences and PET. The aim of this article is to describe oral squamous cell
      carcinoma as it appears in different imaging methods considering both their
      advantages and limitations.

PMID- 28439325
TI  - Graph Frequency Analysis of Brain Signals.
AB  - This paper presents methods to analyze functional brain networks and signals from
      graph spectral perspectives. The notion of frequency and filters traditionally
      defined for signals supported on regular domains such as discrete time and image
      grids has been recently generalized to irregular graph domains, and defines brain
      graph frequencies associated with different levels of spatial smoothness across
      the brain regions. Brain network frequency also enables the decomposition of
      brain signals into pieces corresponding to smooth or rapid variations. We relate
      graph frequency with principal component analysis when the networks of interest
      denote functional connectivity. The methods are utilized to analyze brain
      networks and signals as subjects master a simple motor skill. We observe that
      brain signals corresponding to different graph frequencies exhibit different
      levels of adaptability throughout learning. Further, we notice a strong
      association between graph spectral properties of brain networks and the level of
      exposure to tasks performed, and recognize the most contributing and important
      frequency signatures at different levels of task familiarity.

PMID- 28439326
TI  - Strengthening health systems in communities: the experiences of Amref Health
      Africa.

PMID- 28439327
TI  - Accessibility to sexual and reproductive health and rights education among
      marginalized youth in selected districts of Tanzania.
AB  - INTRODUCTION: Access to information, education and services is central in the
      promotion of sexual and reproductive health and rights (SRHR) among young people.
      It enables young people make informed choices on sexuality matters, hence reduce
      teenage pregnancies and sexually transmitted infections (STIs). This study
      assessed accessibility of SRH rights' information among marginalized young people
      in three municipalities of Iringa, Ilala and Kinondoni in Tanzania. METHODS: A
      cross-sectional study design using mixed methods was conducted in 2013 in three
      selected districts of Tanzania. We randomly selected 398 young people including
      those with disabilities to partake in quantitative survey while 48 community
      members were purposely selected for qualitative part. Quantitative data analysis
      was done using descriptive statistics and chi square test with the assistance of
      the Statistical Package for Social Science(SPSS) version 20, while qualitative
      data was thematically analyzed. RESULTS: There were 396 (99%) participants (144
      Males and 251 females), with a mean age of 20.1years. The majority were out of
      school female, cohabiting and had completed secondary education. Overall, 317
      (79.6%) had SRH rights knowledge. The leading sources of SRH rights information
      were peer educators (36.7%) and radio (22.8%). Awareness regarding laws and
      policies related to SRH right was 55.1%. However, young people living with HIV
      and school truants had more access to SRHR education and services than the other
      youth groups(chi2 30.69, p< 0.0001). The qualitative study revealed that parents
      and teachers perceived themselves to be incompetent in providing SRH information
      to their youngsters despite of being mostly trusted. CONCLUSION: Access to SRH
      rights information is high but decreases when it is disaggregated across
      different age groups. There is a need for diversified approach for reaching
      specific groups of young people depending on their needs and circumstances.

PMID- 28439328
TI  - Reproductive health service utilization and associated factors: the case of north
      Shewa zone youth, Amhara region, Ethiopia.
AB  - INTRODUCTION: Many youth are less informed, less experienced and less comfortable
      in utilizing reproductive health services. In the Sub-Saharan region the
      adolescents account for a higher proportion of new HIV infections and unmet need
      for reproductive health (RH) services. This study assessed reproductive health
      service utilization and associated factors among the youth in Amhara Region,
      Ethiopia. METHODS: A community based cross-sectional study was conducted from
      June 15-July 30, 2014. Three hundred ninety one youth were selected by systematic
      random sampling technique and interviewed using structured questionnaire. Data
      were anlyzed using SPSS windows version 20. Multiple logistic regression was done
      to control potential confounding variables. P-values <0.05 were considered
      statistically significant. RESULTS: Three hundred and nighty one in-school and
      out-of-school youth were interviewed; 256 (65.5%) participants were in school and
      209 (53.5%) were males. Almost all respondents (93.9%) had heard about
      reproductive health services and a third 129 (33%) had ever practiced sexual
      intercourse and 54.7% of them had utilized at least one reproductive health
      services. Never had sexual intercourse (AOR=3.693, 95%CI: 1.266, 10.775),
      families that asked their children about friends (parental monitoring)
      (AOR=1.892, 95%CI: 1.026, 3.491), know where service provided (AOR=3.273, 95%CI:
      1.158, 9.247), youths who reads newspaper readers (AOR=3.787, 95%CI: 1.849were
      independent predictors of youth reproductive service utilization at 95 % CI and p
      value <0.05%. CONCLUSION: Even though the youth have information about
      reproductive health services, youth reproductive health services utilization is
      very low. Therefore, building life skill, facilitating parent to child
      communication, establishing and strengthening of youth centres and increasing
      awareness for youth about those services are important steps to improve
      adolescents' reproductive health (RH) service utilization.

PMID- 28439329
TI  - Food banking for improved nutrition of HIV infected orphans and vulnerable
      children; emerging evidence from quality improvement teams in high food insecure
      regions of Kiambu, Kenya.
AB  - INTRODUCTION: Estimated 236,548 People Living with HIV (PLHIV) were in Central
      Eastern Kenya in 2013. Kiambu County had 46,656 PLHIV with 42,400 (91%) adults
      and 4,200(9%) children (1-14yrs). Amref Health Africa in Kenya, supported through
      USAID-APHIAplus KAMILI project, initiated two food banks to respond to poor
      nutritional status of the HIV infected children. Quality Improvement Teams were
      used to facilitate food-banking initiatives. The study aimed at assessing and
      demonstrating roles of community food-banking in improving nutrition status of
      HIV-infected children in food insecure regions. METHODS: A pre and post-test
      study lasting 12 months (Oct 2013 to September 2014) conducted in Kiambu County,
      Kenya covering 103 HIV infected children. Two assessments were conducted before
      and after the food banking initiative and results compared. Child Status Index
      (CSI) and the Middle Upper Arm Circumference (MUAC) tools were used in data
      collection at households. Paired T-test and Wilcoxon test were applied for
      analysing MUAC and CSI scores respectively using the SPSS. RESULTS: There was a
      significant improvement in the children's nutrition status from a rating of 'bad'
      in CSI Median (IQR) score 2(2-1) before food banking to a rating of 'fair' in CSI
      Median (IQR) score 3(4-3) after food banking intervention (p=<0.001) while MUAC
      increased from Mean (SD) of 5.6(2.6) before intervention to 7.2(2.8) after food
      banking (p=<0.001). CONCLUSION: Food banking is a community-based nutritional
      intervention that can address factors of food access, affordability and
      availability. Food banking is a sustainable way to contribute to quality
      nutrition and reduced related deaths among HIV infected children.

PMID- 28439330
TI  - Predictors of multidrug resistant tuberculosis among adult patients at Saint
      Peter Hospital Addis Ababa, Ethiopia.
AB  - INTRODUCTION: The emergence of multi-drug resistant tuberculosis (MDR-TB) has
      become a major public health concern that threatens advances made in global TB
      control efforts. Though the problem is prevalent, it did not receive major
      attention to generate supportive evidence for the prevention and control of MDR
      TB. The aim of this study was to identify predictors of MDR-TB in a national TB
      referral centre in Ethiopia. METHODS: An unmatched, case-control study was
      conducted at St. Peter Hospital to assess risk factors associated with MDR-TB.
      The study included 103 culture proven, MDR-TB patients referred to the hospital
      during the study period (cases) and 103 randomly-selected TB patients with
      confirmed TB who turned negative after treatment (controls). Regressions analyses
      were used to determine the association of variables. RESULTS: The mean age among
      cases and controls was 30.5 (+/-9.26) and 34.73 (+/-11.28) years, respectively.
      The likelihood of having MDR-TB was 20.3 times higher among those who had a any
      previous history of TB treatment (AOR=20.3 [CI 5.13, 80.58]), 15.7 times higher
      among those who had TB more than once (AOR=15.7 [CI 4.18, 58.71]) compared those
      who had once, 6.8 times higher among those who had pulmonary TB (AOR=6.8 [CI
      1.16, 40.17]) and 16.1 times higher for those who had experienced treatment with
      a Category II regimen (AOR=16.1 [CI 2.40, 108.56]). HIV infection was less common
      among cases than controls. CONCLUSION: This study concluded that special
      attention should be given to patients with a history of the following: TB more
      than once, presence of pulmonary TB, and used a Category II treatment regimen, as
      these were all determining factors for MDR-TB. Thus, this study urges the
      development and implementation of well-planned and integrated strategies for MDR
      TB control and prevention in Ethiopia.

PMID- 28439331
TI  - Motivators and barriers to uptake of post-operative voluntary medical male
      circumcision follow-up in Yala division, Siaya County, Kenya.
AB  - INTRODUCTION: Follow-up visits are recommended to all voluntary medical male
      circumcision clients (VMMC), however, adherence is variable. High lost-to-follow
      up cases limit knowledge about clinical status of clients and adverse events.
      This study sought to establish Motivators and Barriers to the Uptake of VMMC post
      operative follow-up services in Siaya County, Kenya. METHODS: 277 clients from
      five VMMC sites in Yala were recruited immediately post-operation to participate
      in a telephone interview between the 21st and 31st day post-surgery during which
      a semi-structured questionnaire was administered. Descriptive and inferential
      statistics was used to analyse quantitative information using SPSS while
      responses from open ended questions were grouped into themes, sieved out, coded
      and analyzed. RESULTS: 137(49.5%) of the 277 participants utilized the follow-up
      services. Health education (31.4%) and emergency reviews/adverse events (24.1%)
      were the main motivation for returning for follow-up while occupational and other
      engagements (29.7%) and presumption of healing (24.6%) were the main barriers.
      Type of facility attended (p=0.0173), satisfaction with the discharge process
      (p=0.0150) and residency in Yala (p<0.001) were statistically significant to the
      respondents' return for follow-up. 85(62.0%) of the participants returned on the
      7th day, 9(6.6%) returned after 7 days, and 43(31.4%) returned before 7 days.
      CONCLUSION: VMMC health education should include and emphasize the benefits of
      follow-up care to the clients and the providers should address the barriers to
      accessing follow-up services. Our results will inform the programme on areas
      identified to improve care for VMMC clients and reduce subsequent lost-to-follow
      up cases.

PMID- 28439332
TI  - Peer communication on sex and sexual health among youths: a case of Debre Berhan
      university, Ethiopia.
AB  - INTRODUCTION: Friends are considered an important source of advice and
      information about sex. Conversations about sex among young people tend to
      generate norms that influence positive or negative pressure on individuals to
      conform to group standards. The aim of the study was to explore peer
      communication on sex and sexual health. METHODS: Grounded theory qualitative
      study design was employed using focus group discussions and participant
      observation. Participants were selected using criterion purposive sampling. Semi
      structured guides and checklists were used as data collection tools. Information
      was audio-recorded and transcribed verbatim and uploaded to ATLAS.ti 7 software
      for coding. Data collection and analysis were undertaken simultaneously using
      constant comparative analysis. RESULTS: Students talked with peers and sexual
      partners about sex more than sexual health issues. Common places of talk included
      dormitory, begtera (near dorm where students meet), and space (reading rooms).
      Whereas, time of talk, either in a group or with just their close friends or sex
      partners, included during training, evening and weekend time, during walking
      together, and break time. Students used verbal and non-verbal and formal and
      informal communication styles. CONCLUSION: The content, place, and time for
      discussions about sex were influenced by gender, social-cultural norms (e.g.
      religion), rural vs urban living, and the occurrence of sexual health issues
      (e.g, sexually-transmitted infections or unwanted pregnancies). Priority should
      be given to designing audience-specific strategies and messages to promote
      discussions about sex and to encourage safe sexual practices. Primary target
      groups should include female and rural students, who are predisposed to risky
      sexual behavior.

PMID- 28439333
TI  - Determinants of health facility delivery among women in Tharaka Nithi county,
      Kenya.
AB  - INTRODUCTION: Kenya records a high maternal mortality ratio 362 maternal deaths
      per 100 000 live births. Tharaka Sub County has poor transport infrastructure,
      low levels of socio-economic status and long distances to health facilities.
      Secondary to these factors, delivering in a health facility is a challenge.
      Delivering in a health facility is one of the strategies to avert maternal death
      through skilled birth attendance. The aim of the study was to evaluate the
      determinants of health facility delivery among women in Tharaka Nithi County.
      METHODS: The study design was descriptive cross sectional survey. Semi structured
      questionnaires were used for data collection. Stratified sampling was used to
      select the facilities. Systematic sampling was used to select the respondents.
      The sample size was 345. Descriptive statistics, chi square, Fishers exact and
      logistic regression were used in analysis. RESULTS: Majority (79%) of the
      respondents delivered in health facilities. Health facility deliveries were
      highest (80%) among women aged 20-34 years and among those who attended level 4
      facilities for ante natal care (88.3%). Health facility deliveries were lowest
      among women with five or more births. Health facility deliveries were higher
      among those who attended at least 4 ante natal visits (87.2%) and having
      individual birth plans (90%). The likelihood of health facility deliveries was
      increased by increase in level of education (1.6 times), household income (2.4
      times), attending a higher level facility ante natally (1.4 times), birth
      preparedness (3 times), attending at least 4 ante natal visits (2.9 times) but
      was decreased by an increase in parity (0.5 times). CONCLUSION: The determinants
      of place of delivery are maternal age, level of education, household income,
      parity, attendance of ante natal care four or more times and birth preparedness.

PMID- 28439334
TI  - A scorecard for assessing functionality of community health unit in Kenya.
AB  - INTRODUCTION: In 2005, Kenya's Ministry of Health (MOH) in its quest to improve
      health outcomes developed the Community Health Strategy (CHS) as a key approach.
      The MOH and partners grappled with the challenge of managing the functionality of
      the Community Health Units (CHUs). Amref Health Africa in Kenya developed a
      replicable CHUs Functionality Scorecard for measuring and managing the
      functionality of CHUs. METHODS: We designed and piloted the CHU Functionality
      Scorecard at 114 CHUs in Rift valley province in Kenya. The scorecard categorized
      CHUs as Functional, Semi-functional, or Non-Functional. We used before and after
      design to assess the functionality of the CUs. RESULTS: Over seven quarters
      (January 2012 to September 2013). The proportion of functional CHU increased from
      3.5% to 82.9%, Semi-Functional reduced from 39% to 13% while Non-Functional
      reduced from 58% to 4%. The greatest improvements were noted in Community Health
      Volunteers (CHVs) receiving stipends, CHVs with referral booklets, monthly
      dialogue days, actions planning, chalk boards, and CHVs reporting rates.
      CONCLUSION: The CHU functionality scorecard is a valuable tool for the management
      of performance, resource allocation, and decision making. We recommend the
      adoption of the Functionality Scorecard by the Kenya Government for country-wide
      application. We recommend: further work in defining Advanced Functionality and
      incorporating the same into the scorecard; and implementation research on long
      term sustainability of CHUs.

PMID- 28439335
TI  - Facility factors influencing utilization of active management of third stage of
      labour among skilled birth attendants in Kiambu county, Kenya.
AB  - INTRODUCTION: Post-Partum Hemorrhage (PPH) accounts for 34% of maternal deaths in
      Kenya. Active management of third stage of labour (AMTSL) is a World Health
      Organization and Ministry of Health of Kenya approved protocol for reducing
      maternal mortality and morbidity arising from post-partum hemorrhage. Kiambu
      County in Kenya records an average of six maternal deaths per month, out of
      which, two are due to PPH. This paper analyses how facility factors influence
      utilization of this protocol in Kiambu County. METHODS: This was a cross
      sectional study among 431 skilled birth attendants in 52 health facilities. Two
      hundred and three birth attendants were selected using multistage sampling. Data
      was collected using questionnaires and observation checklists and analyzed using
      STATA version 11. Chi square, Fisher's exact and Logistic regressions tests were
      used. RESULTS: AMTSL was utilized by 31.5% of the birth attendants. Controlled
      cord traction (96.5%) was the most utilized. Uterine message after every 15
      minutes was the least utilized component. Utilization was more in government
      facilities (37.4%) (Logistic regression p=0.006) and in level four health
      facilities (49.5%) (p<0.001). Utilization was higher (34.7%) among birth
      attendants who experienced less frequent stock outs (p=0.027) and in facilities
      with more than two staff authorized to order supplies (34.9%) (p=0.020).
      Utilization was higher in facilities with a fridge (44.5%) (p=0.001) and in
      facilities with standards documents in the labour ward (68.0%) (p=0.001).
      CONCLUSION: Health facility factors significantly influence utilization of AMTSL
      and therefore the county government should put in place strategies to enhance the
      factors that influence utilization of AMTSL positively.

PMID- 28439336
TI  - Trends of preeclampsia/eclampsia and maternal and neonatal outcomes among women
      delivering in addis ababa selected government hospitals, Ethiopia: a
      retrospective cross-sectional study.
AB  - INTRODUCTION: The burden of preeclampsia has been a major concern worldwide,
      particularly in developing countries such as Ethiopia. Preeclampsia is associated
      with substantial maternal complications, both acute and long-term. The aim of
      this research was to determine the magnitude and trends of preeclampsia/
      eclampsia, maternal complications, and neonatal complications among women
      delivering babies at selected government hospitals in Ethiopia. METHODS: Data
      were collected retrospectively by reviewing the five-year medical records for
      2009 to 2013, using data abstraction tools, to identify mothers with
      preeclampsia/eclampsia. A total of 1,809 cases were reviewed for general
      characteristics of the mother, delivery details, and any complications.
      Descriptive analyses were employed. In addition, extended Mantel Haenszel chi
      square for linear trend was used to check for significance of the trends.
      RESULTS: The five year average proportion of preeclampsia/eclampsia was 4.2%
      (95%CI 4.02%, 4.4%). The proportion of women with preeclampsia was 2.2% in 2009
      and increased to 5.58% in 2013 (p<0.001), which was a 154% increase. Of the 1,809
      mothers with preeclampsia/eclampsia, 36% (95%CI 33.85%, 38.28%) experienced at
      least one maternal complication; there was an increase of 26.5% (p<0.01) over the
      five year period. The main complications were HELLP (variant of preeclampsia with
      hemolysis, elevated liver enzymes, and low platelet count) syndrome, 257 (39.5%);
      aspiration pneumonia, 114 (17.5%); pulmonary edema, 114 (17.5%); and abruption
      placentae, 100 (15.3%). At least one neonatal complication occurred in 66.4%
      (95%CI 64.24%, 68.59%) of deliveries during the five-year study. A decreasing
      trend in neonatal complications was observed from 2009 (76%) to 2013 (66%), which
      showed a percentage change over time of negative 13.2%. The most common neonatal
      complications were stillbirths, which accounted for 363 (30.2%); prematurity,
      with 395 (32.8%); respiratory distress syndrome, with 456 (37.9%); and low birth
      weight, with 363 (30.2%). CONCLUSION: There was an increasing trend of
      preeclampsia/eclampsia and maternal complications over a five year period in
      selected maternity governmental hospitals. In contrast, neonatal complications
      experienced a significant decrease over the five-year period. It is essential to
      raise awareness among mothers in the community regarding early signs and symptoms
      of preeclampsia/eclampsia and to design a better tracking system for antenatal
      care programs.

PMID- 28439337
TI  - Knowledge, attitudes and practices of traditional birth attendants in pastoralist
      communities of Laikipia and Samburu counties, Kenya: a cross-sectional survey.
AB  - INTRODUCTION: Current efforts to reduce maternal and newborn mortality focus on
      promoting institutional deliveries with skilled birth attendants (SBAs), and
      discouraging deliveries at home attended by traditional birth attendants (TBAs).
      In rural Kenya, semi-nomadic pastoralist communities are underserved by the
      formal health system, experience high maternal and neonatal mortality, and rely
      primarily on TBAs for delivery care, despite Government proscription of TBA
      assisted births. This study examined the knowledge, attitude and practices of
      TBAs serving these communities to assess the potential for collaboration between
      TBAs and SBAs. METHODS: A cross-sectional, interviewer-administered survey was
      conducted among 171 TBAs from Maasai and Samburu pastoralist communities in
      Laikipia and Samburu counties, Kenya, as part of a larger mixed-methods study in
      partnership with a local service provider. RESULTS: BAs were relatively elderly
      (mean age 59.6 years), and attended an average of 5-6 deliveries per year. A
      minority (22.2%) had received formal training. They provided antenatal, intra
      partum and post-partum care. Most TBA care was non-interventionist, but not
      necessarily consistent with best practice. Most had encountered birth
      complications, but knowledge regarding management of complications was sub
      optimal. Most had previously referred at least one woman to a health facility
      (80.1%), were key participants in decision making to refer women (96.5%), and had
      been present at an institutional delivery (54.4%). CONCLUSION: TBAs continue to
      be key providers of maternal and neonatal healthcare in regions where the formal
      health system has poor coverage or acceptability. Strengthening existing TBA/SBA
      collaborations could improve both community links to the formal health system,
      and the quality of care provided to pastoralist women, while remaining consistent
      with current Government policy.

PMID- 28439338
TI  - Factors influencing the utilization of focused antenatal care services in Malindi
      and Magarini sub-counties of Kilifi county, Kenya.
AB  - INTRODUCTION: Globally, pregnancy related complications contribute to more than
      half of the deaths among women annually. Antenatal care (ANC) is important for
      the prevention of maternal and fetal mortality and morbidity. This study
      identifies the socio-demographic and economic characteristics; knowledge and
      attitude and; health service provision for focused antenatal care (FANC)
      services. METHODS: A cross-sectional comparative study conducted among 385 women
      of reproductive age who visited 5 public health facilities in Malindi and
      Magarini Sub Counties. Data collection was conducted between June 2013 and
      September 2013 through structured questionnaires, Key Informant Interviews (KIIs)
      and Focused Group Discussions (FGDs) and analyzed through descriptive summary
      statistics and test of associations of the various variables using chi square.
      RESULTS: About 35% of women sought 1st and 2nd ANC services at the health
      facilities. These women went ahead to complete the recommended 4 minimum visits
      as recommended by World Health Organization (WHO). Compared to Catholics, Muslims
      were less likely to attend a rural health facility (Odds ratio (OR) = 0.25, 95%
      Confidence Interval (CI) 0.10, 0.62, p=0.003). According to education levels,
      those with secondary (OR=0.07, 95% CI 0.03, 0.18, p<0.001) or tertiary (OR=0.09,
      95% CI 0.03-0.17, p<0.001) levels of education were less likely to seek FANC at
      rural facility. Women seeking rural ANC services started at 2nd or 3rd trimester
      (OR=5.40 95% CI 2.97-10.06, p<0.001) while those in urban setup start at 1st
      trimester. Among the women who were aware of FANC, only 27% utilized its
      services. Long waiting hours, unavailability of services, and departmental
      disharmony were major causes of dissatisfaction to mothers visiting the
      facilities. CONCLUSION: Utilization and awareness of FANC services in both rural
      and urban health facilities among women in Malindi and Magarini Sub Counties
      continues to be low which is associated by socio-demographic characteristics, and
      health facility inefficiencies. Thus there is need to standardize services across
      health facilities and increase awareness on FANC in both rural and urban.

PMID- 28439339
TI  - Association between stage at diagnosis and knowledge on cervical cancer among
      patients in a Kenyan tertiary hospital: a cross-sectional study.
AB  - INTRODUCTION: In Kenya, cervical cancer is the second most common cancer among
      women; almost half of all women with invasive cervical cancer are diagnosed at a
      late stage. Few women are aware of the symptoms and risk factors of cervical
      cancer and that its precursor lesions are detectable through screening thus most
      women seek treatment when the cancer is at an advanced stage. The study explored
      the influence of cervical cancer awareness on stage at diagnosis in patients
      attending Kenyatta National Hospital. METHODS: A cross-sectional survey was
      adapted to obtain socio-demographic information, knowledge on symptoms and risk
      factors from 361 women with histological diagnosis of cervical cancer
      conveniently sampled at Kenyatta National Hospital. Associations between stage at
      diagnosis and knowledge on cervical cancer were tested using chi-square statistic
      and fisher's exact test at 95% confidence interval. RESULTS: Seven in every 10
      women (72.6%) presented with advanced stage cervical cancer. Knowledge on the
      sexually transmitted nature of cervical cancer was inadequate, 22% of women with
      early stage and 23.7% of women with advanced stage cervical cancer (p=0.874).
      Majority of the women were not aware of the causative link between cervical
      cancer and human papillomavirus (HPV), 8 (13.1%) of women with early stage and 5
      (3.5%) of women with advanced stage cervical cancer (p=0.036). CONCLUSION: Stage
      at presentation was advanced and knowledge on the role of a sexually transmitted
      virus in the cervical cancer aetiology was poor among the women. Increasing
      screening programs and providing information highlighting this association is
      necessary.

PMID- 28439340
TI  - The Role of IL-17 in the Pathogenesis and Treatment of Psoriasis.

PMID- 28439341
TI  - Secukinumab: Review of Clinical Evidence from the Pivotal Studies ERASURE,
      FIXTURE, and CLEAR.

PMID- 28439342
TI  - Secukinumab in the Treatment of Palmoplantar, Nail, Scalp, and Pustular
      Psoriasis.

PMID- 28439343
TI  - Deciding to Refer Residents for Psychiatric Evaluation.

PMID- 28439344
TI  - A Lesson From the Qualitative Rip Out Series: Let Go of Expectations for
      Universally Applicable "Gold Standards" for Qualitative Research.

PMID- 28439345
TI  - Trainee Involvement in Patient Care: A Necessity and Reality in Teaching
      Hospitals.

PMID- 28439346
TI  - Cognitive Demands and Bias: Challenges Facing Clinical Competency Committees.

PMID- 28439347
TI  - R2C2 in Action: Testing an Evidence-Based Model to Facilitate Feedback and
      Coaching in Residency.
AB  - BACKGROUND: Feedback is increasingly seen as a collaborative conversation between
      supervisors and learners, where learners are actively and reflectively engaged
      with feedback and use it to improve. Based on this, and through earlier research,
      we developed an evidence- and theory-informed, 4-phase model for facilitating
      feedback and practice improvement-the R2C2 model (relationship, reaction,
      content, coaching). OBJECTIVE: Our goal was to explore the utility and
      acceptability of the R2C2 model in residency education, specifically for engaging
      residents in their feedback and in using it to improve, as well as the factors
      influencing its use. METHODS: This qualitative study used the principles of
      design research. We recruited residents and their supervisors in 2 programs,
      internal medicine and pediatrics. We prepared supervisors to use the R2C2 model
      during their regular midrotation and/or end-of-rotation feedback sessions with
      participating residents to discuss their progress and assessment reports. We
      conducted debriefing interviews with supervisors and residents after each
      session. We analyzed transcripts as a team using template and content analysis.
      RESULTS: Of 61 residents, 7 residents (11%) participated with their supervisors
      (n = 5). Schedules and sensitivity to feedback prevented broader enrollment.
      Supervisors found the structured R2C2 format useful. Residents and supervisors
      reported that the coaching phase was novel and helpful, and that the R2C2 model
      engaged both groups in collaborative, reflective, goal-oriented feedback
      discussions. CONCLUSIONS: Participants found that using the R2C2 model enabled
      meaningful feedback conversations, identification of goals for improvement, and
      development of strategies to meet those goals.

PMID- 28439348
TI  - Feedback: The Need for Meaningful Conversations.

PMID- 28439349
TI  - Internal Medicine Program Directors' Perceptions of the "All In" Match Rule: A
      Cross-Sectional Survey.
AB  - BACKGROUND: Since 2013, the National Resident Matching Program (NRMP) has asked
      all programs to declare themselves to be "all in" or "all out" for the NRMP.
      Before this rule was enacted, program directors who were surveyed expressed
      concerns about what they anticipated with the change, including resources for
      increased applications and potential delays with residency start times.
      OBJECTIVE: This study investigated the positive and negative effects of the rule
      change on recruiting seen from the perspective of internal medicine (IM) program
      directors. METHODS: In this mixed model cross-sectional survey, Accreditation
      Council for Graduate Medical Education-accredited IM program directors were
      surveyed regarding their impressions of the impact of the policy change. Data
      were aggregated using constant comparative analysis. RESULTS: A total of 127 of
      396 (32%) IM program directors responded, and 122 of 127 (96%) identified their
      program as "all in." A total of 110 respondents expressed impressions of the rule
      change, with 48% (53 of 111) reporting positive responses, 28% (31 of 111)
      neutral responses, and 24% (27 of 111) negative responses. Programs with higher
      percentages of visa-holding residents had lower positive responses (37% [22 of
      60] versus 61% [31 of 51]). Resident quality was felt to be unchanged or improved
      by most program directors (93%, 103 of 111), yet 24% (27 of 112) reported
      increases in delayed start times for visa-holding residents. Qualitative analysis
      identified increased fairness, at the expense of an increase in program resources
      as a result of the change. CONCLUSIONS: A slight majority of residency programs
      reported a neutral or negative impression of the rule change. Since the rule
      change, program directors noted increased application volume and delayed
      residency starts for visa-holding residents.

PMID- 28439350
TI  - Transgender-Related Education in Plastic Surgery and Urology Residency Programs.
AB  - BACKGROUND: With increasing public awareness of and greater coverage for gender
      confirming surgery by insurers, more transgender patients are likely to seek
      surgical transition. The degree to which plastic surgery and urology trainees are
      prepared to treat transgender patients is unknown. OBJECTIVE: We assessed the
      number of hours dedicated to transgender-oriented education in plastic surgery
      and urology residencies, and the impact of program director (PD) attitudes on
      provision of such training. METHODS: PDs of all Accreditation Council for
      Graduate Medical Education-accredited plastic surgery (91) and urology (128)
      programs were invited to participate. Surveys were completed between November
      2015 and March 2016; responses were collected and analyzed. RESULTS: In total,
      154 PDs (70%) responded, and 145 (66%) completed the survey, reporting a yearly
      median of 1 didactic hour and 2 clinical hours of transgender content. Eighteen
      percent (13 of 71) of plastic surgery and 42% (31 of 74) of urology programs
      offered no didactic education, and 34% (24 of 71) and 30% (22 of 74) provided no
      clinical exposure, respectively. PDs of programs located in the southern United
      States were more likely to rate transgender education as unimportant or neutral
      (23 of 37 [62%] versus 39 of 105 [37%]; P = .017). PDs who rated transgender
      education as important provided more hours of didactic content (median, 1 versus
      0.75 hours; P = .001) and clinical content (median, 5 versus 0 hours; P < .001).
      CONCLUSIONS: A substantial proportion of plastic surgery and urology residencies
      provide no education on transgender health topics, and those that do, provide
      variable content. PD attitudes toward transgender-specific education appear to
      influence provision of training.

PMID- 28439351
TI  - Residents' Exposure to Educational Experiences in Facilitating Hospital
      Discharges.
AB  - BACKGROUND: There is an incomplete understanding of the most effective approaches
      for motivating residents to adopt guideline-recommended practices for hospital
      discharges. OBJECTIVE: We evaluated internal medicine (IM) residents' exposure to
      educational experiences focused on facilitating hospital discharges and compared
      those experiences based on correlations with residents' perceived responsibility
      for safely transitioning patients from the hospital. METHODS: A cross-sectional,
      multi-center survey of IM residents at 9 US university- and community-based
      training programs in 2014-2015 measured exposure to 8 transitional care
      experiences, their perceived impact on care transitions attitudes, and the
      correlation between experiences and residents' perceptions of postdischarge
      responsibility. RESULTS: Of 817 residents surveyed, 469 (57%) responded. Teaching
      about care transitions on rounds was the most common educational experience
      reported by residents (74%, 327 of 439). Learning opportunities with
      postdischarge patient contact were less common (clinic visits: 32%, 142 of 439;
      telephone calls: 12%, 53 of 439; and home visits: 4%, 18 of 439). On a 1-10 scale
      (10 = highest impact), residents rated postdischarge clinic as having the highest
      impact on their motivation to ensure safe transitions of care (mean = 7.61).
      Prior experiences with a postdischarge clinic visit, home visit, or telephone
      call were each correlated with increased perceived responsibility for
      transitional care tasks (correlation coefficients 0.12 [P = .004], 0.1 [P =
      .012], and 0.13 [P =  001], respectively). CONCLUSIONS: IM residents learn to
      facilitate hospital discharges most often through direct patient care.
      Opportunities to interact with patients across the postdischarge continuum are
      uncommon, despite correlating with increased perceived responsibility for
      ensuring safe transitions of care.

PMID- 28439352
TI  - Preoperative Practice Paired With Instructor Feedback May Not Improve Obstetrics
      Gynecology Residents' Operative Performance.
AB  - BACKGROUND: There is evidence that preoperative practice prior to surgery can
      improve trainee performance, but the optimal approach has not been studied.
      OBJECTIVE: We sought to determine if preoperative practice by surgical trainees
      paired with instructor feedback improved surgical technique, compared to
      preoperative practice or feedback alone. METHODS: We conducted a randomized
      controlled trial of obstetrics-gynecology trainees, stratified on a simulator
      assessed surgical skill. Participants were randomized to preoperative practice on
      a simulator with instructor feedback (PPF), preoperative practice alone (PP), or
      feedback alone (F). Trainees then completed a laparoscopic salpingectomy, and the
      operative performance was evaluated using an assessment tool. RESULTS: A total of
      18 residents were randomized and completed the study, 6 in each arm. The mean
      baseline score on the simulator was comparable in each group (67% for PPF, 68%
      for PP, and 70% for F). While the median score on the assessment tool for
      laparoscopic salpingectomy in the PPF group was the highest, there was no
      statistically significant difference in assessment scores for the PPF group
      (32.75; range, 15-36) compared to the PP group (14.5; range, 10-34) and the F
      group (21.25; range, 10.5-32). The interrater correlation between the video
      reviewers was 0.87 (95% confidence interval 0.70-0.95) using the intraclass
      correlation coefficient. CONCLUSIONS: This study suggests that a surgical
      preoperative practice with instructor feedback may not improve operative
      technique compared to either preoperative practice or feedback alone.

PMID- 28439353
TI  - Improving Timely Resident Follow-Up and Communication of Results in Ambulatory
      Clinics Utilizing a Web-Based Audit and Feedback Module.
AB  - BACKGROUND: Failure to follow up and communicate test results to patients in
      outpatient settings may lead to diagnostic and therapeutic delays. Residents are
      less likely than attending physicians to report results to patients, and may face
      additional barriers to reporting, given competing clinical responsibilities.
      OBJECTIVE: This study aimed to improve the rates of communicating test results to
      patients in resident ambulatory clinics. METHODS: We performed an internal
      medicine, residency-wide, pre- and postintervention, quality improvement project
      using audit and feedback. Residents performed audits of ambulatory patients
      requiring laboratory or radiologic testing by means of a shared online interface.
      The intervention consisted of an educational module viewed with initial audits,
      development of a personalized improvement plan after Phase 1, and repeated real
      time feedback of individual relative performance compared at clinic and program
      levels. Outcomes included results communicated within 14 days and prespecified
      "significant" results communicated within 72 hours. RESULTS: A total of 76 of 86
      eligible residents (88%) reviewed 1713 individual ambulatory patients' charts in
      Phase 1, and 73 residents (85%) reviewed 1509 charts in Phase 2. Follow-up rates
      were higher in Phase 2 than Phase 1 for communicating results within 14 days and
      significant results within 72 hours (85% versus 78%, P < .001; and 82% versus
      70%, P = .002, respectively). Communication of "significant" results was more
      likely to occur via telephone, compared with communication of nonsignificant
      results. CONCLUSIONS: Participation in a shared audit and feedback quality
      improvement project can improve rates of resident follow-up and communication of
      results, although communication gaps remained.

PMID- 28439354
TI  - Residents' Procedural Experience Does Not Ensure Competence: A Research
      Synthesis.
AB  - BACKGROUND: Many medical certifying bodies require that a minimum number of
      clinical procedures be completed during residency training to obtain board
      eligibility. However, little is known about the relationship between the number
      of procedures residents perform and their clinical competence. OBJECTIVE: This
      study evaluated associations between residents' medical procedure skills measured
      in a simulation laboratory and self-reported procedure experience and year of
      training. METHODS: This research synthesis extracted and summarized data from
      multiple cohorts of internal medicine, emergency medicine, anesthesiology, and
      neurology resident physicians who performed simulated clinical procedures. The
      procedures were central venous catheter insertion, lumbar puncture, paracentesis,
      and thoracentesis. We compared residents' baseline simulated performance to their
      self-reported procedure experience using data from 7 research reports written by
      Northwestern University investigators between 2006 and 2016. We also evaluated
      how performance differed by postgraduate year (PGY). RESULTS: A total of 588
      simulated procedures were performed during the study period. We found significant
      associations between passing the skills examinations and higher number of self
      reported procedures performed (P = .011) and higher PGY (P < .001). However,
      performance for all procedures was poor, as only 10% of residents passed the
      assessments with a mean of 48% of checklist items correct (SD = 24.2). The
      association between passing the skills examination and year of training was
      mostly due to differences between PGY-1 and subsequent years of training.
      CONCLUSIONS: Despite positive associations between self-reported experience and
      simulated procedure performance, overall performance was poor. Residents'
      clinical experience is not a proxy for skill.

PMID- 28439355
TI  - Using the Entrustable Professional Activities Framework in the Assessment of
      Procedural Skills.
AB  - BACKGROUND: The entrustable professional activity (EPA) framework has been
      identified as a useful approach to assessment in competency-based education. To
      apply an EPA framework for assessment, essential skills necessary for entrustment
      to occur must first be identified. OBJECTIVE: Using an EPA framework, our study
      sought to (1) define the essential skills required for entrustment for 7 bedside
      procedures expected of graduates of Canadian internal medicine (IM) residency
      programs, and (2) develop rubrics for the assessment of these procedural skills.
      METHODS: An initial list of essential skills was defined for each procedural EPA
      by focus groups of experts at 4 academic centers using the nominal group
      technique. These lists were subsequently vetted by representatives from all
      Canadian IM training programs through a web-based survey. Consensus (more than
      80% agreement) about inclusion of each item was sought using a modified Delphi
      exercise. Qualitative survey data were analyzed using a framework approach to
      inform final assessment rubrics for each procedure. RESULTS: Initial lists of
      essential skills for procedural EPAs ranged from 10 to 24 items. A total of 111
      experts completed the national survey. After 2 iterations, consensus was reached
      on all items. Following qualitative analysis, final rubrics were created, which
      included 6 to 10 items per procedure. CONCLUSIONS: These EPA-based assessment
      rubrics represent a national consensus by Canadian IM clinician educators. They
      provide a practical guide for the assessment of procedural skills in a competency
      based education model, and a robust foundation for future research on their
      implementation and evaluation.

PMID- 28439356
TI  - Impact of the 2003 ACGME Resident Duty Hour Reform on Hospital-Acquired
      Conditions: A National Retrospective Analysis.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education reforms in
      2003 instituted an 80-hour weekly limit for resident physicians. Critics argue
      that these restrictions have increased handoffs among residents and the potential
      for a decline in patient safety. "Never events" hospital-acquired conditions
      (HACs) are a set of preventable events used as a quality metric in hospital
      safety analyses. OBJECTIVE: This analysis evaluated post-work hour reform effects
      on HAC incidence for US hospital inpatients, using the National Inpatient Sample.
      METHODS: Data were collected from 2000-2002 (pre-2003) and 2004-2006 (post-2003)
      time periods. HAC incidence in academic and non-academic centers was evaluated in
      multivariate analysis assessing for likelihood of HAC occurrence, prolonged
      length of stay (pLOS), and increased total charges. RESULTS: The data encompassed
      approximately 111 million pre-2003 and 117 million post-2003 admissions. Patients
      were 10% more likely to incur a HAC in the post-2003 versus pre-2003 era (odds
      ratio [OR] = 1.10; 95% confidence interval [CI] 1.06-1.14; P < .01). Teaching
      hospitals exhibited an 18% (OR = 1.18; 95% CI 1.11-1.27; P < .01) increase in HAC
      likelihood, with no change in nonteaching settings (OR = 1.03; 95% CI 1.00-1.06;
      P > .05). Patients with >= 1 HAC were associated with a 60% likelihood of
      elevated charges (OR = 1.60; 95% CI 1.50-1.72; P < .01) and 65% likelihood of
      pLOS (OR = 1.65; 95% CI 1.60-1.70; P < .01). CONCLUSIONS: Post-2003 era patients
      were associated with 10% increased likelihood of HAC, with effects noted
      primarily at teaching hospitals.

PMID- 28439357
TI  - Resident Dyads Providing Transition Care to Adolescents and Young Adults With
      Chronic Illnesses and Neurodevelopmental Disabilities.
AB  - BACKGROUND: Youth with special health care needs often experience difficulty
      transitioning from pediatric to adult care. These difficulties may derive in part
      from lack of physician training in transition care and the challenges health care
      providers experience establishing interdisciplinary partnerships to support these
      patients. OBJECTIVE: This educational innovation sought to improve pediatrics and
      adult medicine residents' interdisciplinary communication and collaboration.
      METHODS: Residents from pediatrics, medicine-pediatrics, and internal medicine
      training programs participated in a transitions clinic for patients with chronic
      health conditions aged 16 to 26 years. Residents attended 1 to 4 half-day clinic
      sessions during 1-month ambulatory rotations. Pediatrics/adult medicine resident
      dyads collaboratively performed psychosocial and medical transition consultations
      that addressed health care navigation, self-care, and education and vocation
      topics. Two to 3 attending physicians supervised each clinic session (4 hours)
      while concurrently seeing patients. Residents completed a preclinic survey about
      baseline attitudes and experiences, and a postclinic survey about their
      transitions clinic experiences, changes in attitudes, and transition care
      preparedness. RESULTS: A total of 46 residents (100% of those eligible)
      participated in the clinic and completed the preclinic survey, and 25 (54%)
      completed the postclinic survey. A majority of respondents to the postclinic
      survey reported positive experiences. Residents in both pediatrics and internal
      medicine programs reported improved preparedness for providing transition care to
      patients with chronic health conditions and communicating effectively with
      colleagues in other disciplines. CONCLUSIONS: A dyadic model of collaborative
      transition care training was positively received and yielded improvements in
      immediate self-assessed transition care preparedness.

PMID- 28439358
TI  - The Trials of Transition: How Well We Are Doing, and How We Can Do Better.

PMID- 28439359
TI  - Education in Neurology Resident Documentation Using Payroll Simulation.
AB  - BACKGROUND: Approaches for teaching neurology documentation include didactic
      lectures, workshops, and face-to-face meetings. Few studies have assessed their
      effectiveness. OBJECTIVE: To improve the quality of neurology resident
      documentation through payroll simulation. METHODS: A documentation checklist was
      created based on Medicaid and Medicare evaluation and management (E/M)
      guidelines. In the preintervention phase, neurology follow-up clinic charts were
      reviewed over a 16-week period by evaluators blinded to the notes' authors.
      Current E/M level, ideal E/M level, and financial loss were calculated by the
      evaluators. Ideal E/M level was defined as the highest billable level based on
      the documented problems, alongside a supporting history and examination. We
      implemented an educational intervention that consisted of a 1-hour didactic
      lecture, followed by e-mail feedback "paystubs" every 2 weeks detailing the
      number of patients seen, income generated, income loss, and areas for
      improvement. Follow-up charts were assessed in a similar fashion over a 16-week
      postintervention period. RESULTS: Ten of 11 residents (91%) participated. Of 214
      charts that were reviewed preintervention, 114 (53%) had insufficient
      documentation to support the ideal E/M level, leading to a financial loss of 24%
      ($5,800). Inadequate documentation was seen in all 3 components: history (47%),
      examination (27%), and medical decision making (37%). Underdocumentation did not
      differ across residency years. Postintervention, underdocumentation was reduced
      to 14% of 273 visits (P < .001), with a reduction in the financial loss to 6%
      ($1,880). CONCLUSIONS: Improved documentation and increased potential
      reimbursement was attained following a didactic lecture and a 16-week period in
      which individual, specific feedback to neurology residents was provided.

PMID- 28439360
TI  - Psychiatry Residents' Perceptions and Reported Practices in Providing Primary
      Care.
AB  - BACKGROUND: Patients with psychiatric disorders have higher rates of chronic
      medical conditions and decreased life expectancy. Integrating medical and
      psychiatric care is likely to improve health outcomes for these patients.
      OBJECTIVE: This study examined what proportion of psychiatry residents viewed
      psychiatry as a primary care specialty, how important they felt it was to provide
      primary care to patients, and how this perception altered self-reported comfort
      and practice patterns in providing screening and treatment for select general
      medical conditions. METHODS: An online survey was sent to current psychiatry
      residents of US residency programs. RESULTS: A total of 268 residents from 40
      programs completed the survey (25% response rate), with 55% (147 of 265) of
      respondents considering psychiatry to be a primary care specialty. Residents who
      held this opinion gave higher ratings for the importance of providing preventive
      counseling and reported counseling a higher percentage of patients on a variety
      of topics. They also reported screening more patients for several medical
      conditions. Residents who considered psychiatry to be primary care did not report
      greater comfort with treating these conditions, with the exception of
      dyslipidemia. The most commonly cited barrier to integrating primary care
      services was lack of time. CONCLUSIONS: Residents' perceptions of psychiatry as a
      primary care field appears to be associated with a higher reported likelihood of
      counseling about, and screening for, medical conditions in their patients.

PMID- 28439361
TI  - Impact of a Video-Based Interactive Workshop on Unprofessional Behaviors Among
      Internal Medicine Residents.
AB  - BACKGROUND: Unprofessional behaviors undermine the hospital learning environment
      and the quality of patient care. OBJECTIVE: To assess the impact of an
      interactive workshop on the perceptions of and self-reported participation in
      unprofessional behaviors. METHODS: We conducted a pre-post survey study at 3
      internal medicine residency programs. For the workshop we identified
      unprofessional behaviors related to on-call etiquette: "blocking" an admission,
      disparaging a colleague, and misrepresenting a test as urgent. Formal debriefing
      tools were utilized to guide the discussion. We fielded an internally developed
      20-item survey on perception and participation in unprofessional behaviors prior
      to the workshop. An online "booster" quiz was delivered at 4 months postworkshop,
      and the 20-item survey was repeated at 9 months postworkshop. Results were
      compared to a previously published control from the same institutions, which
      showed that perceptions of unprofessional behavior did not change and
      participation in the behaviors worsened over the internship. RESULTS: Of 237
      eligible residents, 181 (76%) completed both pre- and postsurvey. Residents
      perceived blocking an admission and the misrepresentation of a test as urgent to
      be more unprofessional at a 9-month follow-up (2.0 versus 1.74 and 2.63 versus
      2.28, respectively; P < .05), with no change in perception for disparaging a
      colleague. Participation in unprofessional behaviors did not decrease after the
      workshop, with the exception of misrepresenting a test as urgent (61% versus 50%,
      P = .019). CONCLUSIONS: The results of this multi-site study indicate that an
      interactive workshop can change perception and may lower participation in some
      unprofessional behaviors.

PMID- 28439363
TI  - Developing Your Expertise as a Peer Reviewer.

PMID- 28439362
TI  - Use of a 90-Minute Admission Window and Front-Fill System to Reduce Work
      Compression on a General Medicine Inpatient Teaching Service.
AB  - BACKGROUND: Duty hour limits have shortened intern shifts without concurrent
      reductions in workload, creating work compression. Multiple admissions during
      shortened shifts can result in poor training experience and patient care.
      OBJECTIVE: To relieve work compression, improve resident satisfaction, and
      improve duty hour compliance in an academic internal medicine program. METHODS:
      In 2014, interns on general ward services were allotted 90 minutes per admission
      from 3 pm to 7 pm, when the rate of admissions was high. Additional admissions
      arriving during the protected period were directed to hospitalists. Resident
      teams received 2 patients admitted by the night float team to start the call day
      (front-fill). RESULTS: Of the 51 residents surveyed before and after the
      implementation of the intervention, 39 (77%) completed both surveys. Respondents
      reporting an unmanageable workload fell from 14 to 1 (P < .001), and the number
      of residents reporting that they felt unable to admit patients in a timely manner
      decreased from 14 to 2 (P < .001). Reports of adequate time with patients
      increased from 16 to 36 (P < .001), and residents indicating that they had time
      to learn from patients increased from 19 to 35 (P < .001). Reports of leaving on
      time after call days rose from 12 to 33 (P < .01), and overall satisfaction
      increased from 26 to 35 (P = .002). Results were similar when residents were
      resurveyed 6 months after the intervention. CONCLUSIONS: Call day modifications
      improved resident perceptions of their workload and time for resident learning
      and patient care.

PMID- 28439364
TI  - Mixed Methods in Health Professions Education Scholarship.

PMID- 28439365
TI  - Authors' Reply to "Why the Aversion?"

PMID- 28439366
TI  - Why the Aversion?

PMID- 28439367
TI  - Resident Education Through Blogging and Other Social Media Platforms.

PMID- 28439368
TI  - Championing Mistakes: Reclaiming the Safe Learning Environment for Family
      Centered Bedside Rounds.

PMID- 28439369
TI  - Are We Adequately Preparing Our Trainees to Care for Transgender Patients?

PMID- 28439370
TI  - Appropriateness of Facebook Friending Between Residents and Attending Physicians.

PMID- 28439371
TI  - iCOMPARE: An Intern's Perspective.

PMID- 28439372
TI  - Let Me Tell You a Story: Creating Successful Wellness Initiatives for Residency
      Programs.

PMID- 28439373
TI  - Improving Resident Well-Being and Burnout: The Role of Peer Support.

PMID- 28439374
TI  - The Toddler, the Waiter, and the Captain.

PMID- 28439375
TI  - Kidney Court: Not Just Another Journal Club.

PMID- 28439376
TI  - "Back to Bedside": Residents' and Fellows' Perspectives on Finding Meaning in
      Work.
AB  - BACKGROUND: Physician burnout is common and associated with significant
      consequences for physicians and patients. One mechanism to combat burnout is to
      enhance meaning in work. OBJECTIVE: To provide a trainee perspective on how
      meaning in work can be enhanced in the clinical learning environment through
      individual, program, and institutional efforts. METHODS: "Back to Bedside"
      resulted from an appreciative inquiry exercise by 37 resident and fellow members
      of the ACGME's Council of Review Committee Residents (CRCR), which was guided by
      the memoir When Breath Becomes Air by Paul Kalanithi. The exercise was designed
      to (1) discover current best practices in existing learning environments; (2)
      dream of ideal ways to enhance meaning in work; (3) design solutions that move
      toward this optimal environment; and (4) support trainees in operationalizing
      innovative solutions. RESULTS: Back to Bedside consists of 5 themes for how the
      learning environment can enhance meaning in daily work: (1) more time at the
      bedside, engaged in direct patient care, dialogue with patients and families, and
      bedside clinical teaching; (2) a shared sense of teamwork and respect among
      multidisciplinary health professionals and trainees; (3) decreasing the time
      spent on nonclinical and administrative responsibilities; (4) a supportive,
      collegial work environment; and (5) a learning environment conducive to
      developing clinical mastery and progressive autonomy. Participants identified
      actions to achieve these goals. CONCLUSIONS: A national, multispecialty group of
      trainees developed actionable recommendations for how clinical learning
      environments can be improved to combat physician burnout by fostering meaning in
      work. These improvements can be championed by trainees.

PMID- 28439377
TI  - Mental Health Services in Oman: The Need for More Cultural Relevance.

PMID- 28439378
TI  - Oman Vision 2050 for Health Research: A Strategic Plan for the Future Based on
      the Past and Present Experience.
AB  - Health care delivery in Oman has attained great heights since the modern
      renaissance in 1970. Although the health service had the main impetus all these
      years, the importance of health research began to take place by mid 1990's and is
      now gaining momentum as an important responsibility and activity of the Ministry
      of Health (MoH). Although there has been progressively increasing investment and
      commitment to research activities in the recent Five Year Plan for Health
      Development, it still lags behind in the quality and quantity of research output.
      Lack of factors like adequate infrastructure, dedicated human resources,
      empowerment of existing systems, and societal support for research have adversely
      affected research output. Centre of Studies and Research in MoH has proposed a
      strategic plan, the 'Health Vision 2050 for Health Research' with aim of making
      Oman the regional leader and a research hub of world standards in health
      research. The mission is to promote, facilitate, and conduct high quality health
      research addressing national health priorities to improve health care services
      and enhance the efficiency and effectiveness of the health system, reduce health
      inequity, and contribute to socioeconomic development. The strategy includes
      setting health research priorities, strengthening the health research capacity,
      defining and implementing norms and standards, developing health research
      (quality and quantity), translating evidence into policy, strategy and practice,
      monitoring and coordinating research, financing health research, and evaluating
      the effectiveness of the health research system. It should generate a multifold
      increase in the quality and quantity of health research in Oman, positively
      impacting the health system and health care service.

PMID- 28439379
TI  - Injuries, Violence, and Bullying Among Middle School Students in Oman.
AB  - OBJECTIVES: Injuries account for a substantial proportion of the burden of
      disease in adolescents globally. This paper describes injury rates and associated
      exposures, and risk behaviors in Oman's 2010 Global School-based Student Health
      Survey (GSHS). METHODS: This study used complex samples analysis to examine
      nationally-representative data from 1 606 students in grades eight, nine, and 10
      who participated in the 2010 Oman GSHS. RESULTS: In total, 34.0% of the students
      reported having at least one injury in the past year that caused at least one
      full day abscence from usual activities or required medical treatment. The most
      common injury type reported was a broken bone or dislocated joint. The most
      common injury cause was falling. Additionally, 38.4% of the students reported
      being bullied in the past month, 38.8% reported being physically attacked in the
      past year, and 47.6% reported being in physical fights. Both injured boys and
      girls reported experiencing significantly more bullying, fights, and attacks
      (odds ratio > 2) than their non-injured classmates, even though only 9.6% of
      injured students reported that their most serious injury in the past year was the
      result of an assault, and students reporting assaults did not have significantly
      higher odds of exposure to these types of peer violence. More than half of the
      bullied students reported that the most frequent type of peer victimization they
      experienced was being made fun of with sexual jokes, comments, or gestures.
      Sexual bullying was the most common type of bullying reported by girls and boys.
      CONCLUSIONS: Promoting healthier peer relationships may help to reduce injuries
      in this age group as well as reducing the harmful effects of bullying.

PMID- 28439380
TI  - Cardiovascular Disease Incidence and Risk Factor Patterns among Omanis with Type
      2 Diabetes: A Retrospective Cohort Study.
AB  - OBJECTIVES: Cardiovascular disease (CVD) represents the leading cause of
      morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). Its
      incidence and risk factor patterns vary widely across different diabetic
      populations. This study aims to assess the incidence and risk factor patterns of
      CVD events among Omanis with T2DM. METHODS: A sample of 2 039 patients with T2DM
      from a primary care setting, who were free of CVD at beseline (2009-2010) were
      involved in a retrospective cohort study. Socio-demographic data and traditional
      risk factor assessments at the baseline were retrieved from medical records,
      after which the first CVD outcomes (coronary heart disease, stroke, and
      peripheral arterial disease) were traced from the baseline to December 2015, with
      a median follow-up period of 5.6 years. RESULTS: The overall cumulative incidence
      of CVD was 9.4% with an incidence density of 17.6 per 1000 person-years.
      Prevalence of poor glycemic control, hypertension, obesity, dyslipidemia,
      albuminuria, and current smoking were 40.0%, 56.3%, 39.0%, 77.3%, 18.7%, and
      7.8%, respectively. The univariate survival analysis showed a significant
      association between CVD and the following factors: age, diabetes duration, body
      mass index, glycemic control, hypertension, total serum cholesterol, and
      albuminuria. CONCLUSIONS: This study revealed high incidence of CVD and high
      prevalence of its traditional risk factors among Omanis with T2DM. In addition,
      compared to global studies, important differences in the prevalence of some risk
      factors and their patterns in the univariate association with the cardiovascular
      outcome have been observed.

PMID- 28439381
TI  - Psychometric Properties of an Arabic Safety Attitude Questionnaire (Short Form
      2006).
AB  - OBJECTIVES: There is a widespread interest in exploring healthcare providers'
      attitudes and perceptions about patient safety culture. This study was done to
      determine the reliability and validity of the Arabic version of Safety Attitude
      Questionnaire (SAQ) in Palestinian hospitals. METHODS: This was a methodological
      study and the SAQ was translated into Arabic using the forward-backward
      translation technique. Four Ministry of Health hospitals in the Gaza Strip were
      randomly selected, and proportionate systematic sampling was followed to select
      the participants. Questionnaires were distributed to 370 physicians and nurses.
      Face and content validity were tested, and the content validity index was
      determined using the average approach. Internal consistency was assessed with
      Cronbach's alpha, split-half reliability, and intercorrelation between the
      questionnaire scales. Construct validity was assessed through exploratory and
      confirmatory factor analysis. RESULTS: A total of 339 questionnaires were
      received, giving a response rate of 91.6%. Questionnaire acceptability was good
      and relevant to the study purpose. Cronbach's alpha value was 77.7 (74.7-82.2).
      Goodness of fit indices from the confirmatory factor analysis showed a
      satisfactory model fit: comparative fit of indices (CFI = 0.797), root mean
      square error of approximation (RMSEA = 0.085), and standardized root square
      residual (SRMR = 0.074). Factor analysis with varimax rotation revealed that six
      factors explained 62.3% of the variance. CONCLUSIONS: The Arabic version of SAQ
      (short form 2006) is valid and reliable, and shows a satisfactory model of fit.
      This instrument shows promise to be a sound tool to assess the safety culture in
      Palestinian hospitals.

PMID- 28439382
TI  - Association Between Adiponectin and Insulin Resistance in Diabetic Urolithiasis.
AB  - OBJECTIVES: The prevalence of urolithiasis is increasing worldwide. Diabetes
      mellitus (DM) is characterized by insulin resistance, which increases the risk of
      kidney stone formation. Adiponectin is an insulin-sensitizing and anti
      inflammatory cytokine, which is known to improve glucose tolerance and insulin
      resistance in humans. The association of insulin and adiponectin with kidney
      stones is not clear. Hence, the present study aim to assess the serum levels of
      adiponectin and insulin resistance in DM patients with urolithiasis in comparison
      to those without. METHODS: This study involved two groups, group A consisted of
      30 patients with DM and urolithiasis, and group B consisted of 30 patients with
      DM but without urolithiasis (control group). Biochemical parameters studied were
      serum adiponectin, insulin, glucose, urea, creatinine, and 24 hours urinary
      calcium and phosphate. RESULTS: The serum adiponectin level was significantly
      increased in the diabetic urolithiasis cases (group A) compared to the control
      group (group B). The levels of 24 hours urine calcium and phosphorus were also
      significantly increased in group A. There was no significant difference in serum
      insulin and homeostasis model assessment of insulin resistance between the two
      groups. A negative correlation was seen between serum adiponectin and insulin
      among the cases (r = -0.368 and p = 0.045). CONCLUSIONS: We found that serum
      adiponectin levels are increased in patients with DM and urolithiasis.

PMID- 28439383
TI  - The Association Between Quality of Sleep and Health-related Quality of Life in
      Military and Non-military Women in Tehran, Iran.
AB  - OBJECTIVES: Quality of sleep (QoS) in individuals is affected by their occupation
      and is one of the factors affecting the quality of life (QoL). Few studies have
      evaluated the relationship between QoS and QoL in military women personnel. The
      aim of this study was to assess QoL and QoS, and compare their relationship among
      military and non-military women in Tehran. METHODS: This cross-sectional study
      was carried out on 90 women working in Tehran during 2014, 30 were military
      forces, 30 were military staff, and 30 were civilian organizations staff. The
      female subjects were selected from Amin Police University and Tehran Health
      Insurance Organization using simple random sampling. The 36-Item Short Form
      Health Survey (SF-36) and Pittsburgh Sleep Quality Index (PSQI) were used to
      measure QoL and QoS, respectively. The relationship between QoL and QoS was
      assessed using Pearson's correlation coefficient. RESULTS: The mean scores of QoL
      in the military forces, military staff, and civilian organizations staff were
      58.94+/-17.71, 67.18+/-13.52, and 69.10+/-12.51, respectively. Among the study
      participants, 62.9% of military forces, 20.0% of military staff, and 17.1% of the
      civilian organizations staff had poor QoS. Mental health as one of the dimensions
      of QoL was significantly different between military forces and civilian
      organizations staff. The association between QoL and QoS was statistically
      significant in military forces and military staff women. CONCLUSIONS: Low QoS and
      QoL in the army necessitates that the authorities offer programs and appropriate
      strategies to improve mental health of QoL and promotion of QoS.

PMID- 28439384
TI  - Characteristics of Neonatal Pneumothorax in Saudi Arabia: Three Years'
      Experience.
AB  - OBJECTIVES: To identify the incidence, clinical characteristics, predisposing
      factors, morbidity, and mortality among hospitalized neonates with pneumothorax.
      METHODS: The records of 2 204 infants admitted to the neonatal intensive care
      unit at King Fahad Medical City, Saudi Arabia, between 2011 and 2014 were
      reviewed. All newborns hospitalized in the neonatal intensive care unit with
      pneumothorax were included in the study. Participants were evaluated for baseline
      characteristics, predisposing factors of neonatal pneumothorax (NP), accompanying
      disorders, and mortality. RESULTS: Pneumothorax was diagnosed in 86 patients,
      with an incidence of 3.9%. The most common predisposing factors of NP were bag
      mask ventilation, followed by hypoplastic lung disease, and mechanical
      ventilation. Twenty-five (29.1%) newborns with pneumothorax died. The most common
      accompanying disorder was premature rupture of membrane. On multivariate
      analysis, pulmonary hemorrhage, a birth weight < 2 500 g, and low Apgar score (<
      7) at one minute were independently associated with mortality. CONCLUSIONS: This
      study highlights the extent of NP problems among hospitalized neonates and the
      most common predisposing factors of NP.

PMID- 28439385
TI  - Effects of Tailored Health Education Program on Overweight Elementary School
      Students' Obesity-Related Lifestyle: A School-Based Interventional Study.
AB  - OBJECTIVES: Overweight and obesity are regarded as one of the most serious health
      and nutrition issues worldwide. This is immediately recognizable in both children
      and adolescents. In this study, we aimed to determine the effects of tailored
      education on lifestyle modification in elementary school students in Isfahan.
      METHODS: In a quasi-experimental study, two elementary schools in Isfahan
      District 3, Iran, were randomly selected to determine the intervention and
      comparison groups. Subsequently, 32 students from each school, 64 in total, were
      chosen arbitrarily and included in the study. They filled out the standardized
      questionnaire of physical activity and dietary behaviors before the intervention.
      Following one and four months' educational intervention, they were asked to
      complete the questionnaires once more. RESULTS: The average general lifestyle
      score, one and four months after education, was significantly different between
      the groups (p < 0.001). However, this difference was not significant before the
      intervention ?(p = 0.660). Furthermore, the average lifestyle scores related to
      nutrition and physical activity one and four months after education showed a
      significant difference between the groups (p < 0.001). CONCLUSIONS: Providing
      overweight elementary school students with education about a healthy lifestyle
      improves their general lifestyle and reduces weight. Therefore, it is recommended
      that such interventions are applied to prevent complications associated with
      being overweight in children.

PMID- 28439387
TI  - Angiographic Embolization in the Treatment of Puerperal Hematoma.
AB  - Puerperal hematoma is one of the life threatening obstetrical emergencies.
      Surgical ligation of bleeding vessel may not always be possible for the patients
      who were hemodynamically unstable, hence pelvic arterial angiography may be
      preferred as the first line treatment modality for these cases. Pelvic arterial
      angiography and embolization is a safe, tolerable, and minimally invasive
      treatment modality in the diagnosis and treatment of pelvic hemorrhage. We
      present a case of puerperal hematoma after a normal spontaneous delivery treated
      with bilateral iliac arterial embolization.

PMID- 28439386
TI  - Usefulness of Clinical Prediction Rules, D-dimer, and Arterial Blood Gas Analysis
      to Predict Pulmonary Embolism in Cancer Patients.
AB  - OBJECTIVES: Pulmonary embolism (PE) is seven times more common in cancer patients
      than non-cancer patients. Since the existing clinical prediction rules (CPRs)
      were validated predominantly in a non-cancer population, we decided to look at
      the utility of arterial blood gas (ABG) analysis and D-dimer in predicting PE in
      cancer patients. METHODS: Electronic medical records were reviewed between
      December 2005 and November 2010. A total of 177 computed tomography pulmonary
      angiograms (CTPAs) were performed. We selected 104 individuals based on
      completeness of laboratory and clinical data. Patients were divided into two
      groups, CTPA positive (patients with PE) and CTPA negative (PE excluded). Wells
      score, Geneva score, and modified Geneva score were calculated for each patient.
      Primary outcomes of interest were the sensitivities, specificities, positive, and
      negative predictive values for all three CPRs. RESULTS: Of the total of 104
      individuals who had CTPAs, 33 (31.7%) were positive for PE and 71 (68.3%) were
      negative. There was no difference in basic demographics between the two groups.
      Laboratory parameters were compared and partial pressure of oxygen was
      significantly lower in patients with PE (68.1 mmHg vs. 71 mmHg, p = 0.030).
      Clinical prediction rules showed good sensitivities (88-100%) and negative
      predictive values (93-100%). An alveolar-arterial (A-a) gradient > 20 had 100%
      sensitivity and negative predictive values. CONCLUSIONS: CPRs and a low A-a
      gradient were useful in excluding PE in cancer patients. There is a need for
      prospective trials to validate these results.

PMID- 28439388
TI  - Herlyn-Werner-Wunderlich Syndrome with Ureteric Remnant Abscess Managed
      Laparoscopically: A Case Report.
AB  - Herlyn-Werner-Wunderlich (HWW) syndrome is part of a spectrum of Mullerian duct
      anomalies that occur during embryonic development. The syndrome is characterized
      by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Only
      few cases of this disease were reported worldwide. We present a 23-year-old
      female patient with chronic pelvic pain for years. The patient was diagnosed with
      HWW syndrome with a history of hematocolpos and vaginoplasty at the age of 12.
      Five months later, she sought urgent medical care due to intense pain, and a
      clinical picture suggestive of peritoneal irritation. Clinical condition
      deteriorated and the patient underwent an exploratory laparotomy, which failed to
      identify anything to justify the abdominal pain. Uroculture and blood culture
      were negative. A magnetic resonance imaging showed a tube-shaped formations
      extending from the right retrovesical region to the mesogastrium corresponding to
      the persistence of the mesonephric duct, related to ipsilateral renal agenesis.
      The patient underwent laparoscopic procedure, identifying a right ureteric
      remnant blind ending, with distal and proximal obliteration, filled with purulent
      secretion, which was totally resected. This case differs from the other reported
      cases due to pelvic pain secondary to infection and abscess in ureteric remnant.
      We did not find any case with similar clinical presentation.

PMID- 28439389
TI  - Management of a Viable Cesarean Scar Pregnancy: A Case Report.
AB  - The incidence of cesarean scar pregnancy (CSP), which was extremely rare till
      recent times, has been rising steadily. We have more of such cases being
      published in medical literature now. A 38-year-old woman with a past history of
      previous three cesarean sections presented with five weeks pregnancy and
      complaints of bleeding per vaginum associated with mild lower abdominal
      discomfort. The diagnosis of CSP with a live fetus within the gestational sac was
      made on a transvaginal ultrasound examination and later confirmed with a magnetic
      resonance imaging (MRI). The management involved injecting potassium chloride
      into the gestational sac and a combination of local and systemic methotrexate
      administration. The patient was followed-up by monitoring the beta human
      chorionic gonadotropin level until it reached non pregnant level and followed-up
      with scan and MRI until complete resolution of the pregnancy sac. Due to the
      rarity of this condition, there are no specific guidelines available for its
      management.

PMID- 28439390
TI  - Nosocomial Pseudomonas putida Meningitis: A Case Report and Literature Review.
AB  - We report a case of Pseudomonas putida meningitis in a 26-year-old Nepalese man
      who was admitted to Hamad General Hospital with epidermoid cyst for drainage.
      Ommaya reservoir was placed into the cyst for drainage and externalventricular
      drainage (EVD) was performed. After four days, the patient was transferred to the
      ward in stable condition. His weakness resolved partially and headache severity
      decreased. After three days, the patient developed fever and headache severity
      increased with deterioration of consciousness level. Cerebrospinal fluid (CSF)
      through EVD showed 2 200 leucocytes/uL, protein level of 295 mg/dL, and glucose
      level of < 1.8 mg/dL. Meropenem was started on the patient. Aspirate from Ommaya
      reservoir and CSF showed gram-negative rods and cultures yielded P. putida
      sensitive to cefepime, gentamycin, ciprofloxacin, and amikacin, but resistant to
      meropenem and piperacillin-tazobactam. EVD was replaced and the patient received
      cefepime and ciprofloxacin for 21 days after which he improved and was discharged
      with right sided residual weakness.

PMID- 28439391
TI  - Exploding Head Syndrome with Co-morbid Sleep Apnea.

PMID- 28439392
TI  - Sexual Life in Women with Stress Urinary Incontinence.

PMID- 28439393
TI  - Oman Medical Specialty Board Career and Research Forum 2016: Abstracts.

PMID- 28439394
TI  - Seasonal variation in effects of herbivory on foliar nitrogen of a threatened
      conifer.
AB  - Invasive herbivores can dramatically impact the nitrogen (N) economy of native
      hosts. In deciduous species, most N is stored in stem tissues, while in evergreen
      conifer species N is stored in needles, making them potentially more vulnerable
      to herbivory. In eastern forests of the USA, the long-lived, foundational conifer
      eastern hemlock (Tsuga canadensis) is under the threat of extirpation by the
      invasive hemlock woolly adelgid (HWA: Adelges tsugae). We assessed the impact of
      HWA infestation on the patterns of seasonal foliar N availability in hemlock
      planted in a deciduous forest understory. Over the course of a year, we sampled
      needles and twigs and measured N, carbon (C), C:N ratio, and total protein
      concentrations. Tissue sampling events were timed to coincide with key life
      history transitions for HWA to determine the association between HWA development
      and feeding with these foliar nutrients. In uninfested trees, needle and twig N
      concentrations fluctuated across seasons, indicating the potential importance of
      N storage and remobilization for the N economy of eastern hemlock. Although N
      levels in HWA-infested trees also cycled annually, the degree to which N
      concentrations fluctuated seasonally in tissues was significantly affected by HWA
      feeding. These fluctuations exceeded N levels observed in control trees and
      coincided with HWA feeding. HWA feeding generally increased N concentrations but
      did not affect protein levels, suggesting that changes in N do not occur via
      adelgid-induced protein breakdown. Herbivore-induced mobilization of N to feeding
      sites and its rapid depletion may be a significant contributor to eastern hemlock
      mortality in US forests.

PMID- 28439395
TI  - Antioxidant responses under salinity and drought in three closely related wild
      monocots with different ecological optima.
AB  - Some deleterious effects of drought, soil salinity and other abiotic stresses are
      mediated by the generation of oxidative stress through an increase in reactive
      oxygen species (ROS) that damage cellular membranes, proteins and DNA. In
      response to increased ROS, plants activate an array of enzymatic and non
      enzymatic antioxidant defences. We have correlated the activation of these
      responses with the contrasting tolerance to salinity and drought of three species
      of the genus Juncus, viz. J. maritimus, J. acutus (both halophytes) and J.
      articulatus (salt-sensitive). Both stresses were given for 8 weeks to 6-week-old
      seedlings in a controlled environment chamber. Each stress inhibited growth and
      degraded photosynthetic pigments in the three species with the most pronounced
      effects being in J. articulatus. Salt and water stress also generated oxidative
      stress in all three taxa with J. articulatus being the most affected in terms of
      accumulation of malondialdehyde (a reliable oxidative stress marker). The
      apparent lower oxidative stress in halophytic J. maritimus and J. acutus compared
      with salt-sensitive J. articulatus is explained by a more efficient activation of
      antioxidant systems since salt or water deficiency induced a stronger
      accumulation of antioxidant phenolic compounds and flavonoids in J. maritimus and
      J. acutus than in J. articulatus. Qualitative and quantitative differences in
      antioxidant enzymes were also detected when comparing the three species and the
      two stress treatments. Accordingly, glutathione reductase and superoxide
      dismutase activities increased in the two halophytes under both stresses, but
      only in response to drought in J. articulatus. In contrast, ascorbate peroxidase
      activity varied between and within species according to treatment. These results
      show the relative importance of different antioxidant responses for stress
      tolerance in species with distinct ecological requirements. The salt-sensitive J.
      articulatus, contrary to the tolerant taxa, did not activate enzymatic
      antioxidant responses to salinity-induced oxidative stress.

PMID- 28439396
TI  - Antibiotics impact plant traits, even at small concentrations.
AB  - Antibiotics of veterinary origin are released to agricultural fields via grazing
      animals or manure. Possible effects on human health through the consumption of
      antibiotic exposed crop plants have been intensively investigated. However,
      information is still lacking on the effects of antibiotics on plants themselves,
      particularly on non-crop species, although evidence suggests adverse effects of
      antibiotics on growth and performance of plants. This study evaluated the effects
      of three major antibiotics, penicillin, sulfadiazine and tetracycline, on the
      germination rates and post-germinative traits of four plant species during
      ontogenesis and at the time of full development. Antibiotic concentrations were
      chosen as to reflect in vivo situations, i.e. concentrations similar to those
      detected in soils. Plant species included two herb species and two grass species,
      and represent two crop-species and two non-crop species commonly found in field
      margins, respectively. Germination tests were performed in climate chambers and
      effects on the remaining plant traits were determined in greenhouse experiments.
      Results show that antibiotics, even in small concentrations, significantly affect
      plant traits. These effects include delayed germination and post-germinative
      development. Effects were species and functional group dependent, with herbs
      being more sensitive to antibiotics then grasses. Responses were either negative
      or positive, depending on plant species and antibiotic. Effects were generally
      stronger for penicillin and sulfadiazine than for tetracycline. Our study shows
      that cropland species respond to the use of different antibiotics in livestock
      industry, for example, with delayed germination and lower biomass allocation,
      indicating possible effects on yield in farmland fertilized with manure
      containing antibiotics. Also, antibiotics can alter the composition of plant
      species in natural field margins, due to different species-specific responses,
      with unknown consequences for higher trophic levels.

PMID- 28439397
TI  - Transcriptomic analysis of maternally provisioned cues for phenotypic plasticity
      in the annual killifish, Austrofundulus limnaeus.
AB  - BACKGROUND: Genotype and environment can interact during development to produce
      novel adaptive traits that support life in extreme conditions. The development of
      the annual killifish Austrofundulus limnaeus is unique among vertebrates because
      the embryos have distinct cell movements that separate epiboly from axis
      formation during early development, can enter into a state of metabolic dormancy
      known as diapause and can survive extreme environmental conditions. The ability
      to enter into diapause can be maternally programmed, with young females producing
      embryos that do not enter into diapause. Alternately, embryos can be programmed
      to "escape" from diapause and develop directly by both maternal factors and
      embryonic incubation conditions. Thus, maternally packaged gene products are
      hypothesized to regulate developmental trajectory and perhaps the other unique
      developmental characters in this species. RESULTS: Using high-throughput RNA
      sequencing, we generated transcriptomic profiles of mRNAs, long non-coding RNAs
      and small non-coding RNAs (sncRNAs) in 1-2 cell stage embryos of A. limnaeus.
      Transcriptomic analyses suggest maternal programming of embryos through
      alternatively spliced mRNAs and antisense sncRNAs. Comparison of these results to
      those of comparable studies on zebrafish and other fishes reveals a surprisingly
      high abundance of transcripts involved in the cellular response to stress and a
      relatively lower expression of genes required for rapid transition through the
      cell cycle. CONCLUSIONS: Maternal programming of developmental trajectory is
      unlikely accomplished by differential expression of diapause-specific genes.
      Rather, evidence suggests a role for trajectory-specific splice variants of genes
      expressed in both phenotypes. In addition, based on comparative studies with
      zebrafish, the A. limnaeus 1-2 cell stage transcriptome is unique in ways that
      are consistent with their unique life history. These results not only impact our
      understanding of the genetic mechanisms that regulate entrance into diapause, but
      also provide insight into the epigenetic regulation of gene expression during
      development.

PMID- 28439399
TI  - Posterior reversible encephalopathy syndrome with colitis in a patient treated
      with panitumumab.

PMID- 28439398
TI  - A practical approach to the pharmacological management of hypertension in older
      people.
AB  - Hypertension is the leading cause of cardiovascular (CV) morbidity and mortality
      in adults over the age of 65. The first part of this paper is an overview,
      summarizing the current guidelines on the pharmacological management of
      hypertension in older adults in Europe and the USA, and evidence from key trials
      that contributed to the guidelines. In the second part of the paper, we will
      discuss the major challenges of managing hypertension in the context of
      multimorbidity, including frailty, orthostatic hypotension (OH), falls and
      cognitive impairment that are associated with ageing. A novel 'BEGIN' algorithm
      is proposed for use by prescribers prior to initiating antihypertensive therapy
      to guide safe medication use in older adults. Practical suggestions are
      highlighted to aid practitioners in making rational decisions to treat and
      monitor hypertension, and for considering withdrawal of antihypertensive drugs in
      the complex older person.

PMID- 28439400
TI  - Proton pump inhibitors and risk of readmission and mortality in older patients
      discharged from a tertiary hospital to residential aged care facilities.

PMID- 28439401
TI  - Long non-coding RNA MALAT1 contributes to cell apoptosis by sponging miR-124 in
      Parkinson disease.
AB  - BACKGROUND: Parkinson disease (PD) is the most common movement disturbance
      characterized by the loss of dopaminergic (DA) neurons in midbrain. Metastasis
      associated lung adenocarcinoma transcript 1 (MALAT1) is aberrantly expressed in
      neurons and is involved in the dendritic and synapse development. However, the
      role of MALAT1 and its underlying mechanism in PD remain to be defined. METHODS:
      The expressions of MALAT1 and miR-124 were evaluated by qRT-PCR. N-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and SH-SY5Y cells
      subjected to N-methyl-4-phenylpyridinium (MPP+) were utilized to investigate the
      effect of MALAT1 on PD. TUNEL assay was performed to detect apoptosis of DA
      neurons in PD mice. Flow cytometry analysis was carried out to measure apoptosis
      of SH-SY5Y cells. Caspase3 activity and Cleaved Caspase3 expression were tested
      by caspase3 assay kit and western blot, respectively. TargetScan software and
      luciferase reporter assay were used to explore the relationship between MALAT1
      and miR-124. RESULTS: MALAT1 was up-regulated and miR-124 was down-regulated in
      MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. MALAT1 knockdown attenuated
      MPTP-induced apoptosis of DA neurons in MPTP-induced PD mouse model. MALAT1
      interacted with miR-124 to negatively regulate its expression. MALAT1 knockdown
      suppressed MPP+-induced apoptosis in SH-SY5Y cells, while miR-124 downregulation
      abrogated this effect. Moreover, MALAT1 knockdown improved miR-124 expression in
      MPTP/MPP+ induced models of PD. CONCLUSIONS: MALAT1 promotes the apoptosis by
      sponging miR-124 in mouse models of PD and in vitro model of PD, providing a
      potential theoretical foundation for the clinical application of MALAT1 against
      PD.

PMID- 28439402
TI  - Upregulation of heme oxygenase-1 expression by curcumin conferring protection
      from hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblasts.
AB  - BACKGROUND: Curcumin is a major constituent of rhizomes of Curcuma longa that
      elicits beneficial effects for oxidative damage. The aim of this study was to
      investigate whether curcumin could attenuate hydrogen peroxide (H2O2)-induced
      apoptosis in H9c2 cardiomyoblasts and the underlying mechanisms. RESULTS: The
      present study showed that exposure of H9c2 cells to H2O2 caused a significant
      increase in apoptosis as evaluated by flow cytometry analysis and the
      pretreatment of curcumin protected against H2O2-induced apoptosis. Exposure of
      cells with curcumin caused a dose-dependent induction of heme oxygenase-1 (HO-1)
      protein expression. Curcumin also decreased the cleaved caspase-3 (CC3) protein
      expression level and increased the Bcl-2/Bax ratio in H2O2-stimulated H9c2 cells.
      ZnPP-IX, a HO-1 inhibitor, partly reversed the anti-apoptotic effect of curcumin.
      Further, LY294002, an inhibitor of PI3K, partially reversed the effect of
      curcumin on HO-1 protein induction, leading to the attenuation of curcumin
      mediated apoptosis resistance. CONCLUSION: These results demonstrated that the
      anti-apoptotic function of curcumin required the upregulation of HO-1 protein
      through the PI3K/Akt signaling pathway. Curcumin might be used as a preventive
      and therapeutic agent for treatment of cardiovascular diseases associated with
      oxidative stress.

PMID- 28439403
TI  - Policy entrepreneurship and policy networks in healthcare systems - the case of
      Israel's pediatric dentistry reform.
AB  - BACKGROUND: Can the entry of a policy entrepreneur challenge the equilibrium of a
      policy network and promote changes that might clash with the goals of powerful
      civil-servants and/or interest groups and, if so, why and how? Our goal is to
      examine two sides of the same coin: how does an in-depth analysis of Israel's
      dental care reform enrich our understanding of policy networks and policy
      entrepreneurship? Second, how does the literature on policy networks and policy
      entrepreneurship help us understand this reform? Based on a theoretical framework
      that appears in the literature of policy entrepreneurship and policy networks, we
      analyze the motivations, goals and strategies of the main actors involved in the
      process of reforming pediatric dental care in Israel. We demonstrate how a policy
      entrepreneur navigated within a policy network and managed to promote a reform
      that, until his appearance, no one else in that network had succeeded in
      enacting. METHODS: Our goals are advanced through a case study of a reform in
      pediatric dentistry implemented in Israel in 2010. It rests on textual analyses
      of the literature, reports, committee minutes, parliamentary proceedings, print
      and online media, and updates in relevant legislation and case law between 2009
      and 2015. In addition, the case study draws on the insights of one of the authors
      (TH), who played a role in the reform process. RESULTS: Historical circumstances
      and the Israeli public's longstanding lack of interest in changing the existing
      model as well as interest groups that preferred the dominance of the private
      sector in the dental healthcare system kept that area out of the services
      supplied, universally, under the National Health Insurance Law. This situation
      changed significantly following the publication in 2007 of a policy analysis that
      contributed to shifts in the motivations and balance of power within the policy
      network, which in turn prepared the ground for a policy change. In this
      environment a determined policy entrepreneur, who identified a window of
      opportunity, took the lead and instituted an innovative and far-reaching reform.
      CONCLUSIONS: A policy entrepreneur can leverage external factors as well as the
      previous activities of a policy network that has already matured to create a
      policy change. Such entrepreneurial activity includes maneuvering around
      opponents and overcoming resistance from various stakeholders.

PMID- 28439404
TI  - Prevalence of low back pain in adolescents with idiopathic scoliosis: a
      systematic review.
AB  - BACKGROUND: Adolescent idiopathic scoliosis is the most common spinal deformity
      occurring in adolescents and its established prevalence varies from 2 to 3%.
      Adolescent idiopathic scoliosis has been identified as a potential risk factor
      for the development of low back pain in adolescents. The purpose of this study
      was to systematically review studies of the prevalence of low back pain in
      adolescents with idiopathic scoliosis in order to establish the quality of the
      evidence and determine whether the prevalence estimates could be statistically
      pooled. METHODS: Systematic electronic searches were undertaken in PubMed,
      CINAHL, and CENTRAL without any restrictions. Studies were eligible for inclusion
      if they reported the prevalence of low back pain in adolescents with idiopathic
      scoliosis. Studies were excluded if they detailed the prevalence of pain in post
      surgical subjects or were published in languages other than English or French.
      Data were reported qualitatively, since there was insufficient evidence for
      statistical pooling. RESULTS: The electronic search strategies yielded 1811
      unique studies. Only two studies fulfilled the eligibility criteria. The
      prevalence of low back pain in adolescents with idiopathic scoliosis ranged from
      34.7 to 42.0%. However, these prevalence estimates should be viewed cautiously as
      the included studies were at high risk of bias. CONCLUSION: The results of this
      systematic review indicate that adolescents with idiopathic scoliosis frequently
      experience low back pain. However, there was insufficient evidence to confidently
      estimate low back pain prevalence in adolescents with idiopathic scoliosis and
      further studies are needed in this area.

PMID- 28439405
TI  - The STarT back tool in chiropractic practice: a narrative review.
AB  - BACKGROUND: The Keele STarT Back Tool was designed for primary care medical
      physicians in the UK to determine the risk for persistent disabling pain in
      patients with musculoskeletal pain and to tailor treatments accordingly. In
      medical and physical therapy settings, STarT Back Tool's tailored care plans
      improved patients' low back pain outcomes and lowered costs. OBJECTIVE: Review
      studies using the STarT Back Tool in chiropractic patient populations. METHODS:
      PubMed, The Cochrane Library, Index to Chiropractic Literature, and Science
      Direct databases were searched. Articles written in English, published in peer
      reviewed journals, that studied the STarT Back Tool in patients seeking
      chiropractic care were included. RESULTS: Seven articles were selected based on
      inclusion and exclusion criteria. The STarT Back Tool was feasibly incorporated
      into 19 chiropractic clinics in Denmark. Total STarT Back 5-item score correlated
      moderately with total Bournemouth Questionnaire score. Two studies reported that
      the STarT Back Tool's predictive ability was poor, while another reported that
      the tool predicted outcomes in patients scoring in the medium and high risk
      categories who completed the STarT Back 2 days after their initial visit. A study
      examining Danish chiropractic, medical and physical therapy settings revealed
      that only baseline episode duration affected STarT Back's prognostic ability
      across all care settings. The tool predicted pain and disability in chiropractic
      patients whose episode duration was at least 2 weeks, but not in patients with an
      episode duration <2 weeks. CONCLUSION: While the STarT Back Tool can be
      incorporated into chiropractic settings and correlates with some elements of the
      Bournemouth Questionnaire, its prognostic ability is sometimes limited by the
      shorter low back pain episodes with which chiropractic patients often present. It
      may be a better predictor in patients whose episode duration is at least 2 weeks.
      Studies examining outcomes of stratified care in chiropractic patients are
      needed.

PMID- 28439406
TI  - Angiographic anatomy of the extracranial and intracranial portions of the
      internal carotid arteries in donkeys.
AB  - BACKGROUND: In horses, the extracranial and intracranial pathway of the internal
      carotid artery has been described. The extracranial pathway of the internal
      carotid artery begins at the carotid termination and runs on the dorsal surface
      of the medial compartment of the guttural pouch. Thereafter the internal carotid
      artery passes through the foramen lacerum to continue intracranially, forming
      part of the rostrolateral quadrants of the cerebral arterial circle (Circle of
      Willis). The objectives of this study were to define and record the anatomy of
      the carotid arterial tree and the internal carotid artery in donkeys using
      angiographic techniques. This is a prospective descriptive study on 26 cadaveric
      donkeys. METHODS: Twenty six donkey cadavers of mixed, age, sex and use presented
      for reasons unrelated to disease of the guttural pouch were subjected to carotid
      and cerebral angiography using rotational angiography. Rotational angiographic
      and 3 dimensional multiplanar reconstructive (3D-MPR) findings were verified with
      an arterial latex casting technique followed by dissection and photography.
      RESULTS: The following variations of the carotid arterial tree were identified:
      [1] the internal carotid and occipital arteries shared a common trunk, [2] the
      linguofacial trunk originated from the common carotid artery causing the common
      carotid artery to terminate as four branches, [3] the external carotid artery was
      reduced in length before giving rise to the linguofacial trunk, mimicking the
      appearance of the common carotid artery terminating in four branches, [4] the
      internal carotid artery originated at a more caudal position from the common
      carotid artery termination. CONCLUSION: Veterinarians should be aware that
      considerable variation exists in the carotid arterial tree of donkeys and that
      this variation may differ markedly from that described in the horse.

PMID- 27347385
TI  - A cross-package Bioconductor workflow for analysing methylation array data.
AB  - Methylation in the human genome is known to be associated with development and
      disease. The Illumina Infinium methylation arrays are by far the most common way
      to interrogate methylation across the human genome. This paper provides a
      Bioconductor workflow using multiple packages for the analysis of methylation
      array data. Specifically, we demonstrate the steps involved in a typical
      differential methylation analysis pipeline including: quality control, filtering,
      normalization, data exploration and statistical testing for probe-wise
      differential methylation. We further outline other analyses such as differential
      methylation of regions, differential variability analysis, estimating cell type
      composition and gene ontology testing. Finally, we provide some examples of how
      to visualise methylation array data.

PMID- 28439408
TI  - Risk factors and outcomes of organ-space surgical site infections after elective
      colon and rectal surgery.
AB  - BACKGROUND: Organ-space surgical site infections (SSI) are the most serious and
      costly infections after colorectal surgery. Most previous studies of risk factors
      for SSI have analysed colon and rectal procedures together. The aim of the study
      was to determine whether colon and rectal procedures have different risk factors
      and outcomes for organ-space SSI. METHODS: A multicentre observational
      prospective cohort study of adults undergoing elective colon and rectal
      procedures at 10 Spanish hospitals from 2011 to 2014. Patients were followed up
      until 30 days post-surgery. Surgical site infection was defined according to the
      Centers for Disease Control and Prevention criteria. Oral antibiotic prophylaxis
      (OAP) was considered as the administration of oral antibiotics the day before
      surgery combined with systemic intravenous antibiotic prophylaxis. RESULTS: Of
      3,701 patients, 2,518 (68%) underwent colon surgery and 1,183 (32%) rectal
      surgery. In colon surgery, the overall SSI rate was 16.4% and the organ-space SSI
      rate was 7.9%, while in rectal surgery the rates were 21.6% and 11.5%
      respectively (p < 0.001). Independent risk factors for organ-space SSI in colon
      surgery were male sex (Odds ratio -OR-: 1.57, 95% CI: 1.14-2.15) and ostomy
      creation (OR: 2.65, 95% CI: 1.8-3.92) while laparoscopy (OR: 0.5, 95% CI: 0.38
      0.69) and OAP combined with intravenous antibiotic prophylaxis (OR: 0.7, 95% CI:
      0.51-0.97) were protective factors. In rectal surgery, independent risk factors
      for organ-space SSI were male sex (OR: 2.11, 95% CI: 1.34-3.31) and longer
      surgery (OR: 1.49, 95% CI: 1.03-2.15), whereas OAP with intravenous antibiotic
      prophylaxis (OR: 0.49, 95% CI: 0.32-0.73) was a protective factor. Among patients
      with organ-space SSI, we found a significant difference in the overall 30-day
      mortality, being higher in colon surgery than in rectal surgery (11.5% vs 5.1%, p
      = 0.04). CONCLUSIONS: Organ-space SSI in colon and rectal surgery has some
      differences in terms of incidence, risk factors and outcomes. These differences
      could be considered for surveillance purposes and for the implementation of
      preventive strategies. Administration of OAP would be an important measure to
      reduce the OS-SSI rate in both colon and rectal surgeries.

PMID- 28439410
TI  - The mental health of unemployed Brussels youth: the role of social and material
      resources.
AB  - BACKGROUND: In the aftermath of the 2008 Great Recession, youth unemployment
      rates in the Brussels Capital Region (BCR) increased. The aim of this study is
      firstly to investigate the evolution of the mental health gap between employed
      and unemployed youth and secondly to examine the association of material and
      social resources with mental health of youth entering the labour market in the
      BCR. METHODS: Two data sources are used to answer the research questions: the
      Belgian Health Interview Survey (HIS) data (1997 to 2013; 18- to 29-year-olds; N
      = 5,562), and the authors' own primary data collection among Brussels youth in
      the transition from education to employment (2015; 18- to 29-year-olds; N =
      1,151; BCR-sample). Prevalence ratios, bivariate and multivariate logistic
      regression analyses are used to explore mental distress and possible mental
      disorder amongst this particular group of youth. RESULTS: The results show a
      consistent tendency towards increasing mental health problems for unemployed,
      compared to employed youth in the 1997-2013 period in the three Belgian Regions.
      Both social support and the living arrangements of men are related to mental
      distress and a possible mental disorder. The perception of a poor financial
      situation is related to a possible mental disorder. Our study also found that
      escape-avoidance behaviour is important in explaining both adverse mental health
      outcomes amongst women. CONCLUSIONS: This study suggests that the mental health
      gap between employed and unemployed youth increases and demonstrates the
      importance of material and social resources for the mental health of unemployed
      youth. These results can contribute to discussions on unemployment policies
      targeting vulnerable youth.

PMID- 28439409
TI  - Serial deletion reveals structural basis and stability for the core enzyme
      activity of human glutaminase 1 isoforms: relevance to excitotoxic
      neurodegeneration.
AB  - BACKGROUND: Glutaminase 1 is a phosphate-activated metabolic enzyme that
      catalyzes the first step of glutaminolysis, which converts glutamine into
      glutamate. Glutamate is the major neurotransmitter of excitatory synapses,
      executing important physiological functions in the central nervous system. There
      are two isoforms of glutaminase 1, KGA and GAC, both of which are generated
      through alternative splicing from the same gene. KGA and GAC both transcribe 1-14
      exons in the N-terminal, but each has its unique C-terminal in the coding
      sequence. We have previously identified that KGA and GAC are differentially
      regulated during inflammatory stimulation and HIV infection. Furthermore,
      glutaminase 1 has been linked to brain diseases such as amyotrophic lateral
      sclerosis, Alzheimer's disease, and hepatic encephalopathy. Core enzyme structure
      of KGA and GAC has been published recently. However, how other coding sequences
      affect their functional enzyme activity remains unclear. METHODS: We cloned and
      performed serial deletions of human full-length KGA and GAC from the N-terminal
      and the C-terminal at an interval of approximately 100 amino acids (AAs).
      Prokaryotic expressions of the mutant glutaminase 1 protein and a glutaminase
      enzyme activity assay were used to determine if KGA and GAC have similar
      efficiency and efficacy to convert glutamine into glutamate. RESULTS: When 110
      AAs or 218 AAs were deleted from the N-terminal or when the unique portions of
      KGA and GAC that are beyond the 550 AA were deleted from the C-terminal, KGA and
      GAC retained enzyme activity comparable to the full length proteins. In contrast,
      deletion of 310 AAs or more from N-terminal or deletion of 450 AAs or more from C
      terminal resulted in complete loss of enzyme activity for KGA/GAC. Consistently,
      when both N- and C-terminal of the KGA and GAC were removed, creating a truncated
      protein that expressed the central 219 AA - 550 AA, the protein retained enzyme
      activity. Furthermore, expression of the core 219 AA - 550 AA coding sequence in
      cells increased extracellular glutamate concentrations to levels comparable to
      those of full-length KGA and GAC expressions, suggesting that the core enzyme
      activity of the protein lies within the central 219 AA - 550 AA. Full-length KGA
      and GAC retained enzyme activities when kept at 4  degrees C. In contrast, 219 AA
      - 550 AA truncated protein lost glutaminase activities more readily compared with
      full-length KGA and GAC, suggesting that the N-terminal and C-terminal coding
      regions are required for the stability KGA and GAC. CONCLUSIONS: Glutaminase
      isoforms KGA and GAC have similar efficacy to catalyze the conversion of
      glutamine to glutamate. The core enzyme activity of glutaminase 1 protein is
      within the central 219 AA - 550 AA. The N-terminal and C-terminal coding regions
      of KGA and GAC help maintain the long-term activities of the enzymes.

PMID- 28439414
TI  - Thanks to Partners, Sponsors and Exhibitors.

PMID- 28439411
TI  - 24th UEG Week 2016: Vienna, Austria, October 2016.

PMID- 28439415
TI  - Stretchable Biofuel Cells as Wearable Textile-based Self-Powered Sensors.
AB  - Highly stretchable textile-based biofuel cells (BFCs), acting as effective self
      powered sensors, have been fabricated using screen-printing of customized stress
      enduring inks. Due to synergistic effects of nanomaterial-based engineered inks
      and the serpentine designs, these printable bioelectronic devices endure severe
      mechanical deformations, e.g., stretching, indentation, or torsional twisting.
      Glucose and lactate BFCs with the single enzyme and membrane-free configurations
      generated the maximum power density of 160 and 250 uW cm-2 with the open circuit
      voltages of 0.44 and 0.46 V, respectively. The textile-BFCs were able to
      withstand repeated severe mechanical deformations with minimal impact on its
      structural integrity, as was indicated from their stable power output after 100
      cycles of 100% stretching. By providing power signals proportional to the sweat
      fuel concentration, these stretchable devices act as highly selective and stable
      self-powered textile sensors. Applicability to sock-based BFC and self-powered
      biosensor and mechanically compliant operations was demonstrated on human
      subjects. These stretchable skin-worn "scavenge-sense-display" devices are
      expected to contribute to the development of skin-worn energy harvesting systems,
      advanced non-invasive self-powered sensors and wearable electronics on a
      stretchable garment.

PMID- 28439416
TI  - Burden of hepatocellular carcinoma among hispanics in South Texas: a systematic
      review.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the fastest rising causes of
      cancer-related mortality in the United States (U.S.). Despite improved HCC
      screening and surveillance guidelines, significant race/ethnicity-specific
      disparities in hepatocellular carcinoma remain, disproportionately affecting at
      risk racial minorities in the U.S. The current review aims to provide an updated
      analysis on race/ethnicity-specific disparities in HCC epidemiology with a focus
      on predisposing risk factors. CONCLUSION: Among different race/ethnicities in the
      U.S., Hispanics experienced the greatest burden of HCC, particularly those
      residing in South Texas. It is important to understand that the underlying
      etiologies for these disparities are complex and multi-factorial. Some of these
      risk factors for developing chronic liver disease include non-alcoholic fatty
      liver disease/non-alcoholic steatohepatitis and alcohol use. In addition,
      population genetics, acculturation of ethnic minorities, and access to healthcare
      may be further contributing to the observed disparities in HCC. By increasing
      awareness, improved modalities for screening and surveillance for HCC are
      important in guiding future research for targeted preventive and therapeutic
      interventions.

PMID- 28439418
TI  - Prevention practices influencing frequency of occurrence of vaso-occlusive crisis
      among sickle cell patients in Abeokuta South Local Government Area of Ogun State,
      Nigeria.
AB  - BACKGROUND: Africa is the most affected continent with 200,000 new born affected
      by sickle cell anemia annually with of 5% of under five deaths. Nigeria has the
      largest sickle cell gene pool in the world with about 2% of all babies born to
      Nigerian parents. This study therefore sets out to assess the prevention
      practices influencing the frequency of occurrence of vaso-occlusive crisis among
      patients in Ogun State. METHODS: This study is a descriptive cross-sectional
      study conducted in Abeokuta South Local Government Area Ogun State. A consecutive
      non randomized sampling of all the sickle cell patients that attend the selected
      facilities was recruited into the study. Data were collected with the use of
      questionnaires which were interviewer administered. A total of 415 patients were
      recruited into the study. Statistical analyses were conducted using SPSS for
      Windows version 20.0. RESULT: Two- third [64.8%] of study participants have
      crisis twice or more in a month. The frequency of crisis was statistically
      significantly associated with the age of the child [p = 0.006], use of anti
      malaria prophylaxis [p = 0.006], analgesics [p = 0.0001], taking of plenty fluid
      [p = 0.001] and soothing herbs [p = 0.0001]. Lifestyle factors such as giving
      balance diet [p = 0.217], restriction from strenuous activities [p = 0.08], and
      attending Clinic appointments regularly [p = 0.126] were not statistically
      associated with reduction in the frequency of crisis. Logistic regression
      analysis shows that predictors of frequent crisis were individuals who were using
      prophylaxis antimalarial drugs [OR = 0.12, CI = 0.05-0.33] and analgesics [OR =
      0.15, C.I = 0.06-0.34]. CONCLUSION: The study reveals that majority of the
      participants have high frequency of crisis in a month. Drug prophylaxis rather
      than lifestyle factors may be more important in the prevention of vaso-occlusive
      crisis among sickle cell patients.

PMID- 28439419
TI  - Chronic complications and quality of life of patients living with sickle cell
      disease and receiving care in three hospitals in Cameroon: a cross-sectional
      study.
AB  - BACKGROUND: Sickle Cell Disease (SCD) is associated with chronic multisystem
      complications that significantly influence the quality of life (QOL) of patients
      early in their life. Although sub-Saharan Africa bears 75% of the global burden
      of SCD, there is a paucity of data on these complications and their effects on
      the QOL. We aimed to record these chronic complications, to estimate the QOL, and
      to identify the corresponding risk factors in patients with SCD receiving care in
      three hospitals in Cameroon. METHODS: In this cross-sectional study, a
      questionnaire was used to collect data from consecutive consenting patients.
      Information recorded included data on the yearly frequency of painful crisis, the
      types of SCD, and the occurrence of chronic complications. A 36-Item Short Form
      (SF-36) standard questionnaire that examines the level of physical and mental
      well-being, was administered to all eligible participants. Data were analyzed
      with STATA(r) software. RESULTS: Of 175 participants included, 93 (53.1%) were
      female and 111 (aged >=14 years) were eligible for QOL assessment. The median
      (interquartile range, IQR) age at diagnosis was 4.0 (2.0-8.0) years and the
      median (IQR) number of yearly painful crisis was 3.0 (1.0-7.0). The most frequent
      chronic complications reported were: nocturnal enuresis, chronic leg ulcers,
      osteomyelitis and priapism (30.9%, 24.6%, 19.4%, and 18.3% respectively). The
      prevalence of stroke and avascular necrosis of the hip were 8.0% and 13.1%
      respectively. The median (IQR) physical and mental scores were 47.3 (43.9-58.5)
      and 41.0 (38.8-44.6) respectively. Age and chronic complications such as stroke
      and avascular necrosis were independently associated with poor QOL. CONCLUSIONS:
      In this population of patients living with SCD, chronic complications are
      frequent and their QOL is consequently poor. Our results highlight the need for
      national guidelines for SCD control, which should include new-born screening
      programs and strategies to prevent chronic complications.

PMID- 28439417
TI  - Cell-free and intracellular nucleic acids: new non-invasive biomarkers to explore
      male infertility.
AB  - Male infertility is a devastating problem that affects many couples worldwide.
      However, the molecular mechanisms and causes of idiopathic male infertility
      remain unclear. Circulating cell-free nucleic acids have an important role in
      human physiology and emerging evidence suggests that they play a role in male
      infertility. This review summarizes recent results on cell-free and intracellular
      nucleic acids in male infertility and discusses their potential use as biomarkers
      of male infertility in the clinical practice.

PMID- 28439420
TI  - An unusual cause of fatal rapid-onset ataxia plus syndrome.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating
      disorder of the central nervous system caused by reactivation of the JC-virus and
      is in most cases associated with underlying immunosuppression. Acquired immune
      deficiency syndrome (AIDS) and hematological malignancies are well-known
      predisposing factors for PML. However, in the past ten years, various
      pharmacological agents have been associated with increased risk of PML. Based on
      the phenomenology PML can be divided into the cerebral form and the rare
      cerebellar form. CASE PRESENTATION: Here we describe a man affected by
      polycythemia vera (PCV) that was treated with hydroxyurea (HU) and developed PML.
      The initially PML presentation included ataxia as one of the main features. Brain
      MRI displayed widespread supratentorial and infratentorial lesions. Immunological
      analysis revealed absence of reactivity to a wide range of antigens. The course
      of disease was rapidly progressive with fatal outcome - autopsy ruled out
      leukemic transformation. CONCLUSION: The occurrence of PML in PCV patients is
      very rare and has been reported only once. Movement disorders, such as ataxia,
      are also less frequent. In the present case the PML was likely multifactorial.

PMID- 28439421
TI  - Factors associated with cesarean delivery rates: a single-institution experience.
AB  - BACKGROUND: The aim of this study was to identify factors associated with
      variability in Cesarean delivery (CD) rates amongst providers at a single
      institution. METHODS: A retrospective cohort analysis was carried out on all
      births at NYU Langone Medical Center from 2005-2013. Data was collected for
      subjects and linked to diagnosis codes for singleton and twin deliveries.
      Descriptive characteristics were generated for all deliveries, and inferential
      analysis was performed including multiple covariates for singleton deliveries in
      the 2010-2013 cohort, including both univariate and multivariate regression
      analyses to identify factors associated with higher CD rates. RESULTS: 37,692
      deliveries were identified at our institution during the study period, performed
      by 88 unique providers. The mean CD rate was 29.6%, with a range for individual
      physicians from 9.9% to 75.6%. In multivariate regression analysis, CD rate was
      directly correlated with average patient age, physician male gender, proportion
      of high-risk deliveries, and Maternal-Fetal Medicine specialty, and it was
      inversely correlated with total number of deliveries by physician and forceps
      delivery rate. There was no significant difference in CD rates between group and
      solo practices. Within the same group practice, each member's CD rate was
      strongly correlated with the average CD rate of the group. CONCLUSION: Our study
      demonstrates the wide range of CD rates for providers practicing within the same
      institution and reiterates the association of CD rates with patient age, high
      risk pregnancy, and provider volume. Among operative vaginal deliveries, forceps
      delivery rate was associated with lower CD rates whereas vacuum delivery rate was
      not. Despite these findings, practice patterns within individual practices appear
      to contribute significantly to the wide range of CD rates.

PMID- 28439422
TI  - Anti-aging effect and gene expression profiling of dung beetle glycosaminoglycan
      in aged rats.
AB  - BACKGROUND: This study aimed to evaluate the anti-aging effect of a newly
      prepared insect-derived compound, dung beetle glycosaminoglycan (GAG), given
      intraperitoneally to old SD rats as part of their diet for 1 month. Insect GAG
      administration was found to be related to a reduction in oxidative damage, hepato
      cellular biomarker levels, protein carbonyl content, and malondialdehyde
      concentration. The anti-aging-related molecular genetic mechanisms of dung beetle
      GAG are not yet fully elucidated. RESULTS: Catharsius molossus (a type of dung
      beetle) GAG (CaG) possessed anti-aging activities; it reduced the serum level of
      creatinine kinase, had aortic vasorelaxant activities and cardioprotective
      actions, and maintained a normal glucose level in treated rats. Microarray
      analysis was performed with a rat 30 K cDNA clone set array to identify the gene
      expression profiles of 14-month-old SD rats treated with dung beetle
      glycosaminoglycan 5 mg/kg (CaG5) over a 1-month period, which was done to
      investigate its anti-aging effect as compared to that of either Bombus ignitus (a
      type of bumblebee) queen GAG 5 mg/kg (IQG5) or chondroitin sulfate 10 mg/kg. CaG5
      and IQG5 had marked anti-inflammatory effects, bringing about inhibition of free
      fatty acid, uric acid, sGPT, IL-1 beta, and CK values. In addition, anticoagulant
      and antithrombotic effects were seen: the concentration of factor 1 (fibrinogen)
      was increased in CaG- treated rat plasma. The CaG5-treated rat group, compared to
      the control, displayed upregulation of 131 genes, including lipocalin 2 (Lbp) and
      a serine peptidase inhibitor, Kaszal type3 (Spink3), and 64 downregulated genes,
      including lysyl oxidase (Lox), serine dehydratase (sds), and retinol saturase
      (Retsat). CONCLUSION: Our data suggest that dung beetle glycosaminoglycan may be
      a helpful treatment for aged rats, which indicates its potential as a therapeutic
      biomaterial for aging.

PMID- 28439423
TI  - Rheumatoid arthritis: what do MRI and ultrasound show.
AB  - Rheumatoid arthritis is the most common inflammatory arthritis, affecting
      approximately 1% of the world's population. Its pathogenesis has not been
      completely understood. However, there is evidence that the disease may involve
      synovial joints, subchondral bone marrow as well as intra- and extraarticular fat
      tissue, and may lead to progressive joint destruction and disability. Over the
      last two decades, significant improvement in its prognosis has been achieved
      owing to new strategies for disease management, the emergence of new biologic
      therapies and better utilization of conventional disease-modifying antirheumatic
      drugs. Prompt diagnosis and appropriate therapy have been recognized as essential
      for improving clinical outcomes in patients with early rheumatoid arthritis.
      Despite the potential of ultrasonography and magnetic resonance imaging to
      visualize all tissues typically involved in the pathogenesis of rheumatoid
      arthritis, the diagnosis of early disease remains difficult due to limited
      specificity of findings. This paper summarizes the pathogenesis phenomena of
      rheumatoid arthritis and describes rheumatoid arthritis-related features of the
      disease within the synovium, subchondral bone marrow and articular fat tissue on
      MRI and ultrasound. Moreover, the paper aims to illustrate the significance of
      MRI and ultrasound findings in rheumatoid arthritis in the diagnosis of
      subclinical and early inflammation, and the importance of MRI and US in the
      follow-up and establishing remission. Finally, we also discuss MRI of the spine
      in rheumatoid arthritis, which may help assess the presence of active
      inflammation and complications.

PMID- 28439424
TI  - Comparison of scintigraphy and ultrasound imaging in patients with primary,
      secondary and tertiary hyperparathyroidism - own experience.
AB  - BACKGROUND: The imaging techniques most commonly used in the diagnosis of
      hyperparathyroidisms are ultrasound and scintigraphy. The diagnostic algorithms
      vary, depending mainly on the population, and experience of physicians. AIM: Aim
      of the present research was to determine the usefulness of parathyroid
      scintigraphy and ultrasonography in patients diagnosed for hyperparathyroidism in
      own material. MATERIAL AND METHOD: In the present research, 96 operated patients
      with documented primary, secondary and tertiary hyperparathyroidism were
      retrospectively analyzed. All patients underwent a 99mTc hexakis-2
      methoxyisobutylisonitrile scintigraphy of the neck with the use of subtraction
      and two-phase examinations. Ultrasonography of the neck was performed in all the
      patients in B mode 2D presentation. A total number of 172 parathyroid glands were
      analyzed. RESULTS: The sensitivity and specificity of scintigraphy was 68% and
      60%, respectively. The sensitivity of ultrasound was 49% and specificity 85%.
      Both techniques allowed visualization of 76 parathyroid glands. Ultrasound
      revealed 19 glands that were not visible in scintigraphy. Scintigraphy showed 76
      parathyroid glands that were not visualized on ultrasound. Having combined the
      results of scintigraphy and ultrasound, the sensitivity of 76% and specificity of
      50% were obtained. Considering the ability to locate the parathyroid glands in
      both techniques as a positive result, the sensitivity decreased to 37% and
      specificity rose to 95%. CONCLUSIONS: Scintigraphy showed greater sensitivity
      than ultrasound in the localization of enlarged parathyroid glands. Ultrasound,
      in turn, was characterized by a higher specificity. The combined use of
      scintigraphy and ultrasonography allowed to obtain the specificity of 95%. In the
      light of obtained results, scintigraphy and ultrasonography are complementary and
      should be used together.

PMID- 28439425
TI  - Fetal biometric parameters: Reference charts for a non-selected risk population
      from Uberaba, Brazil.
AB  - OBJECTIVE: To establish reference charts for fetal biometric parameters in a non
      selected risk population from Uberaba, Southeast of Brazil. METHODS: A
      retrospective cross-sectional study was performed among 5656 non-selected risk
      singleton pregnant women between 14 and 41 weeks of gestation. The ultrasound
      exams were performed during routine visits of second and third trimesters.
      Biparietal diameter (BPD) was measured at the level of the thalami and cavum
      septi pellucidi. Head circumference (HC) was calculated by the following formula:
      HC = 1.62*(BPD + occipital frontal diameter, OFD). Abdominal circumference (AC)
      was measured using the following formula: AC = (anteroposterior diameter +
      transverse abdominal diameter) * 1.57. Femur diaphysis length (FDL) was obtained
      in the longest axis of femur without including the distal femoral epiphysis. The
      estimated fetal weight (EFW) was obtained by the Hadlock formula. Polynomial
      regressions were performed to obtain the best-fit model for each fetal biometric
      parameter as the function of gestational age (GA). RESULTS: The mean, standard
      deviations (SD), minimum and maximum of BPD (cm), HC (cm), AC (cm), FDL (cm) and
      EFW (g) were 6.9 +/- 1.9 (2.3 - 10.5), 24.51 +/- 6.61 (9.1 - 36.4), 22.8 +/- 7.3
      (7.5 - 41.1), 4.9 +/- 1.6 (1.2 - 8.1) and 1365 +/- 1019 (103 - 4777),
      respectively. Second-degree polynomial regressions between the evaluated
      parameters and GA resulted in the following formulas: BPD = -4.044 + 0.540 * GA -
      0.0049 * GA2 (R2 = 0.97); HC= -15.420 + 2.024 GA - 0.0199 * GA2 (R2 = 0.98); AC =
      -9.579 + 1.329 * GA - 0.0055 * GA2 (R2 = 0.97); FDL = -3.778 + 0.416 * GA -
      0.0035 * GA2 (R2 = 0.98) and EFW = 916 - 123 * GA + 4.70 * GA2 (R2 = 0.96);
      respectively. CONCLUSION: Reference charts for the fetal biometric parameters in
      a non-selected risk population from Uberaba, Southeast of Brazil, were
      established.

PMID- 28439426
TI  - Is it possible to differentiate between pseudopneumoperitoneum and similar
      pathologies ultrasonographically?
AB  - AIM: The goal of the work was comparing gas ultrasound images below the right
      diaphragm in two groups: in people with intestinal interposition below the
      diaphragm and ones with pneumoperitoneum and extracting the traits
      differentiating these two conditions. MATERIAL AND METHODS: Retrospectively, the
      documentation of 22 patients with intestinal interposition below the diaphragm
      (group 1) was utilized. Clinical material was used for comparison, previously
      published, composed of 15 cases of pneumoperitoneum following laparotomy and of
      14 cases following that symptom as a result of ulcer perforation - group 2 (in
      total n = 29). Moreover, the distance in millimeters of the gas surface
      reflecting ultrasounds from the parietal peritoneum was measured, the smoothness
      of the surface, parietal peritoneum enhancement at the place of gas adherence,
      gas continuity below the diaphragm with gas in the intestine located below the
      liver. RESULTS: Direct adherence of the gas surface to the diaphragm was observed
      in 100% of the cases of emphysema, but in no cases of intestinal interposition.
      Yet, in the group of patients with colonic interposition (n = 21) there was
      always a small gap (2-3 mm) and the gas surface among those patients in 100% of
      the cases was uneven. CONCLUSIONS: In differentiation between pneumoperitoneum
      and liver-diaphragm interposition of the intestine one should take into account -
      apart from gas movement below the diaphragm at body position changing - the
      presence of protrusion and section enhancement of the diaphragmatic peritoneum as
      well as the distance of the gas from the diaphragm, the smoothness of its surface
      and the continuity with the intestine below the liver. Interpositions of small
      diaphragm-liver penetration may subside in erect position.

PMID- 28439427
TI  - Double aorta artifact in sonography - a diagnostic challenge.
AB  - The double aorta artifact was described and studied thoroughly twenty-five years
      ago. Despite this, it is still not commonly known today and can cause diagnostic
      difficulty. Total aortic duplication can be considered an anatomic defect whilst
      partial duplication mimics aortic dissection. In the literature, this artifact
      has been compared with a very rare anomaly, i.e. the occurrence of two aortas in
      one patient. Currently, however, the differentiation of this artifact from
      abdominal aortic dissection seems to be of greater significance. The double aorta
      image occurs when ultrasound waves encounter prismatic fat tissue of the anterior
      abdominal wall. This artifact is more frequently observed in children and
      athletic young adults since the structure of this anatomic region in these
      individuals is conductive to the occurrence of this phenomenon. Moreover, it can
      be observed more often when curved transducers are used. Due to all these
      factors, an ultrasound beam undergoes greater refraction and make the artifact
      clearer. This phenomenon is usually easily recognizable and avoidable, but it
      sometimes might cause diagnostic difficulty. Obtaining an image of double
      abdominal vessels on ultrasound examination in transverse sections requires
      further inspection of the aorta in a different (sagittal) plane. This is not
      always possible due to poor patient preparation for scanning. Symmetrical flow on
      Doppler sonography is a typical feature of this artifact. Finally, magnetic
      resonance imaging or computed tomography can be considered to rule out a
      pathology.

PMID- 28439428
TI  - Current standards in abdominal cavity ultrasound examination in children.
AB  - Technological progress forces us to present after several years the updated
      standards in ultrasound examination of newborns, infants and older children. It
      should be emphasized that the examination of the youngest patients requires one
      to use high-class equipment. Lack of cooperation on the part of the child and
      imaging small structures constitute a huge challenge for the examiner. The work
      presents equipment requirements, the technology of examining the abdominal cavity
      in children and the manner of preparing the examination result. Moreover, modern
      expectations as regards ultrasound surgery equipment, where children are subject
      to examination have been presented. The minimum set of transducers the ultrasound
      apparatus should be equipped with has also been pointed out as well as the
      minimum requirements concerning image recording. Extending the scope of
      transducers over "minimum" significantly raises the imaging possibilities in
      pediatrics. Standard preparation of children for ultrasound has been discussed,
      taking into consideration the age of the patient and indications. It is essential
      to understand that it differs from standard preparation for examination in the
      case of adults. The technique of examining the abdominal cavity has been
      described, which enables the repeatability of examinations and ensuring making
      all the available structures visible. It proves imperative especially in the case
      of a large number of examinations. Attention should be paid particularly to the
      urinary system imaging - owing to the greatest incidence of congenital diseases
      in that system.

PMID- 28439429
TI  - The standards of an ultrasound examination of the prostate gland. Part 2.
AB  - The paper discusses the rules of the proper performing of the ultrasound
      examination of the prostate gland. It has been divided into two parts: the
      general part and the detailed part. The first part presents the necessary
      requirements related to the ultrasound equipment needed for performing
      transabdominal and transrectal examinations of the prostate gland. The second
      part presents the application of the ultrasound examination in benign prostatic
      hyperplasia, in cases of prostate inflammation and in prostate cancer. Ultrasound
      examinations applied in the diagnostics of benign prostatic hyperplasia
      accelerated the diagnosis, facilitated the qualification to surgery and the
      selection of the treatment method. The assessment of the size of the prostate
      gland performed using the endorectal ultrasound examination is helpful in making
      the choice between transurethral electroresection and adenomectomy. In prostate
      inflammation this examination should be performed with particular gentleness due
      to pain ailments. The indication for performing the examination in acute
      inflammation is the suspicion of prostate abscess. In chronic, exacerbating
      prostatitis it is possible to perform an intraprostatic antibiotic injection. In
      the recent years increased morbidity and detectability of prostate gland cancer
      is observed among men. In Poland it ranks second (13%) among diseases occurring
      in men. The indication for an endorectal examination is the necessity to assess
      the size of the prostate gland, its configuration, the echostructure in classical
      ultrasonography, the vascularization in an ultrasound examination performed with
      power doppler and, if possible, the differences in the gland tissue firmness
      (consistency) in elastography. The ultrasound examination is used for performing
      the mapping biopsy of the prostate gland - from routine, strictly defined
      locations, the targeted biopsy - from locations suspected of neoplastic
      proliferation and the staging biopsy - from the neurovascular bundles, the
      seminal vesicles, from the apex of the prostate and from the periprostatic tissue
      - this type of biopsy is supposed to help in determining local staging of the
      neoplastic disease. The ultrasound examination is also helpful during the
      treatment of the neoplasm performed using brachytherapy or using the method of
      ultrasonic ablation which is still in the phase of clinical trials.

PMID- 28439430
TI  - Mistakes in ultrasound diagnosis of superficial lymph nodes.
AB  - The article discusses basic mistakes that can occur during ultrasound imaging of
      superficial lymph nodes. Ultrasound is the first imaging method used in the
      diseases of superficial organs and tissues, including lymph nodes. The causes of
      mistakes can be either dependent or independent of the performing physician. The
      first group of mistakes includes inappropriate interpretation of images of
      anatomical structures, while the latter group includes, among other things,
      similar ultrasound images of different pathologies. For instance, a lymph node,
      whether normal or abnormal, may be mimicked by anatomical structures, such as a
      partially visible, compressed vein. Lymph nodes in lymphomas may be
      indistinguishable from reactive lymph nodes, even when using Doppler option, as
      well as morphologically difficult to distinguish from metastases. Metastatic
      lymph nodes can mimic e.g. nodular, separated postoperative thyroid fragments, a
      lateral neck cyst, chemodectoma (carotid body tumor) or neuroma. The appearance
      of lymph nodes in granulomatous diseases, such as tuberculosis or sarcoidosis,
      can be very similar to that of typical metastatic lymph nodes or lymphomas.
      Anechoic or hypoechoic areas in a lymph node can represent necrosis or metastatic
      hemorrhages, but also suppuration in inflamed lymph nodes. Lymph nodes in
      lymphomas, metastatic and reactive lymph nodes can adopt the classical
      characteristics of a simple cyst. The overall ultrasound picture along with all
      criteria for the assessment of a lymph node should be taken into account during
      ultrasound imaging. It seems that the safest management is to refer patients
      diagnosed with lymph node abnormalities for ultrasound-guided targeted fine
      needle aspiration biopsy followed by a total lymph node resection for
      histopathological examination in the case of suspected lymphoma.

PMID- 28439431
TI  - Mistakes in the ultrasound diagnostics of the abdominal cavity in pediatrics.
AB  - The diagnostics of the abdominal cavity in children, especially in the neonatal
      infantile period, requires knowledge in the field of anatomical and
      physiopathological differences as well as clinical symptomatology and pathology
      at every stage of the child's development. Errors and mistakes in ultrasound
      diagnostics of the abdominal cavity in children result from many factors,
      including lack of experience in examining children and the knowledge concerning
      most frequent ailments and pathologies as well as the incidence or no changes in
      the ultrasound image of the abdominal cavity organs. The assessment of the
      ultrasound image should be always based on clinical data of the patient,
      information on the past diseases, surgeries and the results of additional
      examinations and laboratory tests. Particular attention should be paid to the
      occurrence of congenital diseases and inflammations, which may have varied
      clinical manifestation - especially in the case of pediatric diagnostics. The
      variety and non-specific nature of clinical symptoms may also mask the developing
      neoplastic process. Mistakes in ultrasound diagnostics, especially among the
      youngest children, may also be caused by technical difficulties related to
      carrying out the examination. The above situation results from lack of
      cooperation with the child, who is uneasy, wailing, fails to perform orders,
      which may lead to overlooking the existing lesion or overinterpreting, e.g. a
      full stomach or residual stool in the intestines to be a pathology. It is also of
      high importance to have a good class of the ultrasound equipment and technical
      knowledge concerning its operation. When performing an ultrasound examination in
      children, it is necessary to apply a wide range of phased-array, convex and
      linear heads and appropriate applications, the so-called pediatric software
      (stomach, kidneys, true pelvis, organs at the surface).

PMID- 28439432
TI  - Posterior interosseous nerve palsy caused by a ganglion: Conservative treatment
      with ultrasound-guided needle aspiration.
AB  - Posterior interosseous nerve palsy caused by a ganglion is not common and most
      previous patients were treated with excisional surgery. We treated a case
      conservatively with needle aspiration using ultrasonography, after a nerve
      conduction study. A 77-year-old man presented with impaired active finger
      extension of the left metacarpophalangeal joints. The nerve conduction study
      revealed conduction block of the left radial nerve near the elbow.
      Ultrasonography demonstrated a hypoechoic mass anterior to the radial neck
      compressing the posterior interosseous nerve. Then, needle aspiration of the mass
      was conducted under ultrasonography. Two months later, active finger extension
      recovered to normal. A ganglion can be diagnosed with ultrasonography and needle
      aspiration can be carried out safely under ultrasonography. A nerve conduction
      study can assess the degree of nerve damage. The combination of ultrasonography
      and a nerve conduction study can facilitate conservative treatment of needle
      aspiration for posterior interosseous nerve palsy caused by a ganglion.

PMID- 28439433
TI  - Programmed Intermittent Epidural Boluses (PIEB) for Maintenance of Labor
      Analgesia: A Superior Technique to Continuous Epidural Infusion?

PMID- 28439434
TI  - Programmed Intermittent Epidural Boluses (PIEB): A Superior Technique for
      Maitenance of Labor Analgesia.

PMID- 28439435
TI  - Programmed Intermittent Epidural Boluses (PIEB) for Maintenance of Labor
      Analgesia: A Superior Technique and Easy to Implement.

PMID- 28439436
TI  - Programmed Intermittent Epidural Boluses (PIEB) for Maintenance of Labor
      Analgesia: An Incremental Step Before the Next Paradigm Shift?

PMID- 28439438
TI  - The Complex Process of Haemostasis and Interactions due to Hyperosmotic Fluids.

PMID- 28439437
TI  - Supraglottic Airway Devices: the Search for the Best Insertion Technique or the
      Time to Change Our Point of View?
AB  - In the crowded world of supraglottic airway devices (SADs), many papers compare
      the easiness of insertion based on the different endpoints of an operator's
      satisfaction: first pass success, ventilation effectiveness, complications and
      morbidity. Proseal LMATM (Laryngeal Mask Airway, Teleflex Medical, Dublin,
      Ireland) has been extensively studied because on one hand it has a steeper
      learning curve and more complex insertion when compared with other SADs and on
      the other hand many alternative techniques are available to facilitate insertion.
      This research is part of a larger body of studies exploring the issue that some
      devices are more difficult to insert because of many features related to sizing,
      constructive material, airway conduit and cuff design, performance and last but
      not least experience. Nevertheless, the biggest question might be the search for
      a systematic categorization of insertion difficulty features and identification
      of criteria allowing the choice for the best device and consequently for the best
      insertion technique. Given that, as a result of many intrinsic characteristics of
      the device we are using, insertion might become the secondary issue to be
      considered only after we clearly identify what makes it difficult, and to be
      counterbalanced on the results we expect from the device, performance we can
      achieve and degree of airway protection it could grant. The aim of this narrative
      review is to consider which factors might affect or condition SAD insertion
      difficulty and to try identifying some criteria addressing physicians pertaining
      to the use of SADs in clinical practice.

PMID- 28439439
TI  - Fascial Plane Blocks in Regional Anaesthesia and New Approaches.

PMID- 28439440
TI  - A Comparison of the Effects of 20% Mannitol and 3% NaCl on Coagulation Parameters
      In Vitro using ROTEM: A Prospective Randomized Crossover Study.
AB  - OBJECTIVE: The aim of the present study is to compare the effect of 20% mannitol
      and 3% NaCl on blood coagulation in vitro using rotational thromboelastometry
      (ROTEM). METHODS: Twenty-millilitre blood samples were obtained from 15
      volunteers. In each group, 2 mL blood samples were collected into both
      polypropylene tubes and EDTA tubes for ROTEM and hemogram analysis. After
      sampling, blood samples were diluted with test solutions. Group C (control): Only
      blood, Group M (mannitol): 7% vol 20% mannitol concentration in the blood, Group
      hypertonic saline (HS): 7% vol 3% hypertonic saline (NaCl) in the blood, Group
      M/H (mannitol and hydroxyethyl starch solutions [HES]): 6% vol 20% mannitol
      concentration and 8% vol HES in the blood and Group HS/H (hypertonic saline and
      HES): 6% vol 3% hypertonic saline concentration and 8% vol HES in the blood. The
      following thromboelastometric parameters were measured automatically: clotting
      time (CT) and clot formation time (CFT) with intrinsic activation by tissue
      factor (InTEM), CT, CFT and maximum clot firmness (MCF) with extrinsic activation
      by tissue factor (ExTEM) and MCF with FibTEM. RESULTS: The ExTEM CT value was
      found to be significantly longer in the M/H group than in the controls. The ExTEM
      CFT median and percentile values were: group C: 85 s (70-95 s), group M: 115 s
      (94-128 s), group HS: 102 s (84-114 s), group M/H: 128 s (110-144 s) and group
      HS/H: 118 s (107-132 s). In all the groups, FibTEM MCF values were significantly
      lower than the control and also there was a significant difference between groups
      M and HS according to FibTEM MCF values. CONCLUSION: Whole-blood coagulation
      disorder induced by these solutions is mainly dependent on fibrinogen and fibrin
      interaction. However, 3% HS has much less negative effect on coagulation.

PMID- 28439441
TI  - Comparison of Effects of Low-Flow Sevoflurane and Low-Flow Desflurane Anaesthesia
      on Renal Functions Using Cystatin C.
AB  - OBJECTIVE: Numerous studies have indicated nephrotoxic effects of sevoflurane
      because of its two bioproducts compound A and fluoride. Cystatin C (CyC) is a
      more sensitive biomarker than creatinine to show early and mild changes in kidney
      function. We designed this prospective randomised study to compare the effects of
      low-flow sevoflurane anaesthesia and low-flow desflurane anaesthesia on renal
      functions based on CyC levels. No studies have evaluated the effects of low-flow
      sevoflurane anaesthesia on renal functions based on CyC levels to date. METHODS:
      Thirty American Society of Anesthesiologists (ASA) physical status I-II patients
      who were scheduled for urological procedures were enrolled in this study. The
      patients were randomly assigned to 2 groups: low-flow sevoflurane anaesthesia or
      low-flow desflurane anaesthesia. Serum urea, creatinine and CyC levels were
      measured before the operation, just before extubation and 24 h after the
      operation. Creatinine clearance was calculated in the first 24-h urine sample.
      RESULTS: There were no significant differences in serum urea, creatinine and CyC
      levels or 24 h creatinine clearance between the groups. CONCLUSION: Our study
      demonstrates with a more sensitive biomarker, CyC, that low-flow sevoflurane
      anaesthesia is safe in terms of the effects on renal function.

PMID- 28439442
TI  - A Prospective Randomised Clinical Trial for the Comparison of Two Techniques for
      the Insertion of Proseal Laryngeal Mask Airway in Adults-Index Finger Insertion
      Technique versus 90 degrees  Rotation Technique.
AB  - OBJECTIVE: The 90 degrees  rotation technique for inserting the Proseal laryngeal
      mask airway (PLMA) is reported to be better than the standard index finger
      insertion technique to improve the insertion success rate. The objective of this
      study was to evaluate and compare the ease of insertion through the 90 degrees 
      rotation and standard insertion techniques in terms of number of attempts,
      duration of insertion and occurrence of complications. METHODS: One hundred and
      twenty adult patients were allocated to either a standard technique group or
      rotation technique group with 60 patients in each. In the rotation technique
      group, the entire cuff of the PLMA was placed in the patient's mouth in a midline
      approach without finger insertion, rotated 90 degrees  counter-clockwise around
      the patient's tongue, advanced and rotated back until resistance was felt.
      RESULTS: The success rate of the rotation technique group at the first insertion
      attempt was greater than that of the standard index finger insertion technique
      (98% vs. 78%; p=0.001), and less time for insertion was required (11.88+/-3.62 s
      vs. 25.98+/-10.92 s; p<0.0001). The incidence of post-operative sore throat was
      lower (15% vs. 38.34%; p=0.0067), and blood staining on the PLMA was less (11.7%
      vs. 45%; p<0.0001). The increase in the mean arterial pressure was more in the
      standard technique group. CONCLUSION: The 90 degrees  rotation technique has a
      higher success rate at first insertion attempt for inserting the ProSeal LMA than
      the index finger insertion technique with less time for insertion and fewer side
      effects.

PMID- 28439443
TI  - Role of Ultrasonography in Detecting the Localisation of the Nasoenteric Tube.
AB  - OBJECTIVE: In this study, we aimed to determine the success rate of nasoenteric
      tube (NET) insertion into the postpyloric area using ultrasonography (USG) and
      compare with the commonly used method direct abdominal graphy. METHODS: A single
      anaesthesiologist placed all the NETs. The NET was visualised by two radiologists
      simultaneously using USG. The localisation of the tube was confirmed using an
      abdominal graph in all patients. RESULTS: The blind bedside method was used for
      NET insertion into 34 patients. Eleven of the tubes were detected passing through
      the postpyloric area using USG. In one case, the NET could not be visualised in
      the postpyloric area using USG; however, it was detected in the postpyloric area
      through control abdominal radiography. In 22 patients, NETs were detected in the
      stomach using control abdominal radiography. The rate of imaging post pyloric
      using USG was 91.6%. When all cases were considered, catheter localisation was
      detected accurately using USG by 97% (33 in 34 patients). CONCLUSION: USG is a
      reliable and practical alternative to radiography, which can be used to detect
      localisation of the nasogastric tube and NET.

PMID- 28439444
TI  - Airway Management of Patients Undergoing Oral Cancer Surgery: A Retrospective
      Analysis of 156 Patients.
AB  - OBJECTIVE: Oral cancer patients have a potentially difficult airway, but if
      managed properly during the perioperative period, morbidity and mortality can be
      reduced or avoided. METHODS: The medical records of 156 patients who were
      operated for oral cancers were reviewed for airway management during the
      perioperative period. RESULTS: The surgical procedures ranged from excisions,
      wide local excisions with split skin graftings, hemiglossectomies and radical
      neck nodes dissections to pectoralis major myocutaneous or free fibular flaps.
      Intubation was assessed as difficult in 14.7% of patients because of tumour- or
      radiation fibrosis-related trismus, restricted neck mobility and prior similar
      surgeries. Twenty patients had undergone surgery for oral cancer previously and
      were scheduled for flap reconstruction. Nasotracheal intubation was a preferred
      route, and 62.8% of patients could be intubated nasotracheally after
      neuromuscular blockade. Tracheostomy (elective or existing) was utilised for
      airway control in 19.2% cases. Patients who had undergone prior radiotherapy were
      more likely to be tracheostomised. McCoy laryngoscopes (13.4%), gum elastic
      bougies (23.6%), Airtraq devices (0.006%) and fibreoptic bronchoscopes (FOBs)
      (0.03%) were the additional airway techniques employed. In total, 64 patients
      (50.7%) could be extubated immediately after surgery. CONCLUSION: Proper
      preoperative evaluation and planning help manage difficult airways effectively
      with minimal need of advanced airway gadgets. Gum elastic bougies and Magill
      forceps are very useful in airway management and decrease the need of elective
      tracheostomy in oral cancer patients.

PMID- 28439445
TI  - Ultrasound-Guided Continuous Interpectoral Block for Patient Undergoing
      Mastectomy and Axillary Clearance.
AB  - Using a single dose of local anaesthetics has some disadvantages and provides
      limited analgesia depending on the pharmacokinetic characteristics of the local
      anaesthetic used. Nevertheless, the use of continuous perineural infusions allows
      sustained pain control. Ultrasound-guided interpectoral block followed by the
      placement of catheters in patients undergoing mastectomies with or without lymph
      node axillary dissections can result in sufficient pain control. We present a
      case of a 58-year-old woman undergoing mastectomy and axillary clearance who
      received ultrasound-guided continuous interpectoral block for postoperative
      analgesia. After the induction of general anaesthesia, interpectoral ultrasound
      block was performed and levobupivacaine was administered through a catheter
      placed between the pectoralis minor and pectoralis major muscles using an
      ultrasound-guided technique. We used an elastomeric pump containing the 0.125%
      levobupivacaine anaesthetic solution, with an infusion rate of 5 mL h-1 for 48 h.
      Excellent postoperative pain control was observed. Local anaesthetic- and
      catheter-related side-effects were not observed. The ideal infusion rate for
      interpectoral block in patients under mastectomy has not been determined. More
      randomised studies are needed to confirm whether interpectoral techniques are
      appropriate for routine clinical practice.

PMID- 28439446
TI  - Thoracic Unilateral Spinal Cord Injury After Spinal Anaesthesia for Total Hip
      Replacement: Fate or Mistake?
AB  - Spinal anaesthesia is the most preffered anesthesia technique for total hip
      replacement, and its complications range from low entity (insignificant) to life
      threatening. The incidence of neurologic complications after neuraxial
      anaesthesia is not perfectly clear, although there are several described cases of
      spinal cord ischaemia. We present a case of unilateral T8-T11 spinal cord
      ischaemia following L2-L3 spinal anaesthesia for total hip replacement. Magnetic
      resonance imaging showed a hyperintense T8-T11 signal alteration on the leftside
      of paramedian spinal cord. A temporal epidemiologic linkage between the damage
      and the surgery seems to be present. The injury occurred without anatomical
      proximity between the injury site and the spinal needle entry site. This may be
      due to multiple contributing factors, each of them is probably not enough to
      determine the damage by itself; however, acting simultaneously, they could have
      been responsible for the complication. The result was unpredictable and
      unavoidable and was caused by unforeseeable circumstances and not by inadequate
      medical practice.

PMID- 28439447
TI  - The Development of a Veterans Health Administration Emergency Management Research
      Agenda.
AB  - INTRODUCTION: The Veterans Health Administration (VHA), the largest integrated
      healthcare delivery system in the United States, is charged with ensuring timely
      access to high-quality care for veterans during disasters, and supporting
      national, state, local, and tribal emergency management and homeland security
      efforts. In 2008, the VHA Office of Public Health (OPH) sponsored the first VHA
      Emergency Management Research Agenda-setting conference to develop research
      priorities that address the needs of veterans and to position VHA as a national
      leader in emergency management by having VHA serve as a "laboratory" for the
      development of evidence-based emergency management practices. METHODS: We focused
      on four steps: #1: Appraising the emergency management research portfolio of VHA
      based researchers; #2: Obtaining systematic information on VHA's role in
      emergency management and the healthcare needs of veterans during disasters; #3:
      Based upon gaps between the current research portfolio and the existing evidence
      base, identifying strategic priorities using a research agenda-setting
      conference; and #4: Laying the groundwork to foster the conduct of emergency
      management research within VHA. RESULTS: Identified research priorities included
      how to prevent and treat behavioral health problems related to a disaster, the
      efficacy of training programs, crisis communication strategies, workforce
      resilience, and evacuating veterans from health care facilities. Conclusion: VHA
      is uniquely situated to answer research questions that cannot be readily
      addressed in other settings. VHA should partner with other governmental and
      private entities to build on existing work and establish shared research
      priorities.

PMID- 28439448
TI  - Spatial Determinants of Ebola Virus Disease Risk for the West African Epidemic.
AB  - INTRODUCTION: Although many studies have investigated the probability of Ebola
      virus disease (EVD) outbreaks while other studies have simulated the size and
      speed of EVD outbreaks, few have investigated the environmental and population
      level predictors of Ebola transmission once an outbreak is underway. Identifying
      strong predictors of transmission could help guide and target limited public
      health resources during an EVD outbreak. We examined several environmental and
      population-level demographic predictors of EVD risk from the West African
      epidemic. METHODS: We obtained district-level estimates from the World Health
      Organization EVD case data, demographic indicators obtained from the Demographic
      and Health surveys, and satellite-derived temperature, rainfall, and land cover
      estimates. A Bayesian hierarchical Poisson model was used to estimate EVD risk
      and to evaluate the spatial variability explained by the selected predictors.
      RESULTS:  We found that districts had greater risk of EVD with increasing
      proportion of households not possessing a radio (RR 2.79, 0.90-8.78; RR 4.23,
      1.16-15.93), increasing rainfall (RR 2.18; 0.66-7.20; 5.34, 1.20-23.90), and
      urban land cover (RR 4.87, 1.56-15.40; RR 5.74, 1.68-19.67). DISCUSSION:  The
      finding of radio ownership and reduced EVD transmission risk suggests that the
      use of radio messaging for control and prevention purposes may have been crucial
      in reducing the EVD transmission risk in certain districts, although this
      association requires further study. Future research should examine the etiologic
      relationships between the identified risk factors and human-to-human transmission
      of EVD with a focus on factors related to population mobility and healthcare
      accessibility, which are critical features of epidemic propagation and control.

PMID- 28439449
TI  - Mobilizable genomic islands, different strategies for the dissemination of
      multidrug resistance and other adaptive traits.
AB  - Mobile genetic elements are near ubiquitous DNA segments that revealed a
      surprising variety of strategies for their propagation among prokaryotes and
      between eukaryotes. In bacteria, conjugative elements were shown to be key
      drivers of evolution and adaptation by efficiently disseminating genes involved
      in pathogenicity, symbiosis, metabolic pathways, and antibiotic resistance.
      Conjugative plasmids of the incompatibility groups A and C (A/C) are important
      vehicles for the dissemination of antibiotic resistance and the consequent global
      emergence and spread of multi-resistant pathogenic bacteria. Beyond their own
      mobility, A/C plasmids were also shown to drive the mobility of unrelated non
      autonomous mobilizable genomic islands, which may also confer further
      advantageous traits. In this commentary, we summarize the current knowledge on
      different classes of A/C-dependent mobilizable genomic islands and we discuss
      other DNA hitchhikers and their implication in bacterial evolution. Furthermore,
      we glimpse at the complex genetic network linking autonomous and non-autonomous
      mobile genetic elements, and at the associated flow of genetic information
      between bacteria.

PMID- 28439450
TI  - Peritoneal carcinomatosis of colorectal cancer is characterized by structural and
      functional reorganization of the tumor microenvironment inducing senescence and
      proliferation arrest in cancer cells.
AB  - Background : Peritoneal carcinomatosis (PC) is a terminal evolution from primary
      colorectal cancer (pCRC) associated with poor patient survival. Impact of the
      immune cell infiltrate on PC pathogenesis is unknown. Therefore, we characterized
      the immunological tumor microenvironment regarding proliferation, senescence and
      neovascularization. Methods : Formalin-fixed and paraffin-embedded (FFPE) tissue
      of PC and pCRC was examined by immunohistochemistry. Cells infiltrating resected
      tissue were isolated and analyzed by flow cytometry. PCR arrays detected the
      expression of genes relevant for helper T (TH) cell responses, like TH1, TH2 and
      TH17 response. Results : PC tumor cells demonstrate significantly lower
      proliferation rates than pCRC, but show significantly more senescence. PC is
      surrounded by significantly increased numbers of cytotoxic active Natural Killer
      (NK) cells, follicular helper T cells (TFH) and B cells, whereas pCRC shows more
      CD4+ TH cells, CD8+ cytotoxic T (TC) cells, eosinophilic granulocytes, TH17 and
      regulatory T (Treg) cells. PC is characterized by significantly increased
      interferon-gamma (IFNgamma), an upregulation of tumor necrosis factor (TNF) and
      the NK cell-regulating cytokine interleukin-15 (IL-15). An upregulation of
      angiogenesis-related genes, like vascular endothelial growth factor-A (VEGF-A),
      leads to severe neovascularization in PC. Correlations of PC results reveal that
      elevated numbers of interleukin-17 (IL-17) positive cells are associated with
      high cancer cell proliferation, whereas high numbers of IFNgamma positive cells
      correlate with more tumor cells in senescence. Conclusion : The cellular immune
      reaction is modified during metastasis, inducing senescence in PC tumor cells.
      Immune surveillance in PC is facilitated by NK cells and high levels of IFNgamma
      and TNF. Counteracting this effect, TFH and B cells combined with VEGF-A
      enhancement promote neovascularization in PC (Illustration 1). During metastasis
      from primary CRC to PC the immune cell infiltrate changes, accompanied by the
      induction of senescence in PC cancer cells (marked red): In pCRC, the antitumor
      immune response is facilitated by CD4+TH cells, CD8+TC cells and PRG2+
      eosinophilic granulocytes. The premetastatic niche development is promoted by
      Treg cells and TH17 cells producing systemic factors like VEGF-A, TGF-beta and
      TNF. Along with TFH and B cells, as with a pro-tumor immune response, they
      support metastatic formation and lead to severe neovascularization in PC. This is
      counterbalanced by the IL-15-induced activation and proliferation of NK cells.
      The secreted cytokines IFNgamma and TNF mediate immunosurveillance.

PMID- 28439451
TI  - Automated identification of insect vectors of Chagas disease in Brazil and
      Mexico: the Virtual Vector Lab.
AB  - Identification of arthropods important in disease transmission is a crucial, yet
      difficult, task that can demand considerable training and experience. An
      important case in point is that of the 150+ species of Triatominae, vectors of
      Trypanosoma cruzi, causative agent of Chagas disease across the Americas. We
      present a fully automated system that is able to identify triatomine bugs from
      Mexico and Brazil with an accuracy consistently above 80%, and with considerable
      potential for further improvement. The system processes digital photographs from
      a photo apparatus into landmarks, and uses ratios of measurements among those
      landmarks, as well as (in a preliminary exploration) two measurements that
      approximate aspects of coloration, as the basis for classification. This project
      has thus produced a working prototype that achieves reasonably robust correct
      identification rates, although many more developments can and will be added, and
      more broadly-the project illustrates the value of multidisciplinary
      collaborations in resolving difficult and complex challenges.

PMID- 28439452
TI  - Reporting and methodological quality of meta-analyses in urological literature.
AB  - PURPOSE: To assess the overall quality of published urological meta-analyses and
      identify predictive factors for high quality. MATERIALS AND METHODS: We
      systematically searched PubMed to identify meta-analyses published from January
      1st, 2011 to December 31st, 2015 in 10 predetermined major paper-based urology
      journals. The characteristics of the included meta-analyses were collected, and
      their reporting and methodological qualities were assessed by the PRISMA
      checklist (27 items) and AMSTAR tool (11 items), respectively. Descriptive
      statistics were used for individual items as a measure of overall compliance, and
      PRISMA and AMSTAR scores were calculated as the sum of adequately reported
      domains. Logistic regression was used to identify predictive factors for high
      qualities. RESULTS: A total of 183 meta-analyses were included. The mean PRISMA
      and AMSTAR scores were 22.74 +/- 2.04 and 7.57 +/- 1.41, respectively. PRISMA
      item 5, protocol and registration, items 15 and 22, risk of bias across studies,
      items 16 and 23, additional analysis had less than 50% adherence. AMSTAR item 1,
      "a priori" design, item 5, list of studies and item 10, publication bias had less
      than 50% adherence. Logistic regression analyses showed that funding support and
      "a priori" design were associated with superior reporting quality, following
      PRISMA guideline and "a priori" design were associated with superior
      methodological quality. CONCLUSIONS: Reporting and methodological qualities of
      recently published meta-analyses in major paper-based urology journals are
      generally good. Further improvement could potentially be achieved by strictly
      adhering to PRISMA guideline and having "a priori" protocol.

PMID- 28439453
TI  - Competition and feeding ecology in two sympatric Xenopus species (Anura:
      Pipidae).
AB  - The widespread African clawed frog (Xenopus laevis) occurs in sympatry with the
      IUCN Endangered Cape platanna (Xenopus gilli) throughout its entire range in the
      south-western Cape, South Africa. In order to investigate aspects of the
      interspecific competition between populations of X. laevis and X. gilli, an
      assessment of their niche differentiation was conducted through a comprehensive
      study on food composition and trophic niche structure at two study sites: the
      Cape of Good Hope (CoGH) and Kleinmond. A total of 399 stomach contents of X.
      laevis (n = 183) and X. gilli (n = 216) were obtained together with samples of
      available prey to determine food preferences using the Electivity index (E*), the
      Simpson's index of diversity (1 - D), the Shannon index (H'), and the Pianka
      index (Ojk ). Xenopus gilli diet was more diverse than X. laevis, particularly in
      Kleimond where the Shannon index was nearly double. Both species were found to
      consume large amounts of tadpoles belonging to different amphibian species,
      including congeners, with an overall higher incidence of anurophagy than
      previously recorded. However, X. laevis also feeds on adult X. gilli, thus
      representing a direct threat for the latter. While trophic niche overlap was 0.5
      for the CoGH, it was almost 1 in Kleinmond, suggesting both species utilise
      highly congruent trophic niches. Further, subdividing the dataset into three size
      classes revealed overlap to be higher in small frogs in both study sites. Our
      study underlines the importance of actively controlling X. laevis at sites with
      X. gilli in order to limit competition and predation, which is vital for
      conservation of the south-western Cape endemic.

PMID- 28439454
TI  - Distribution and establishment of the alien Australian redclaw crayfish, Cherax
      quadricarinatus, in South Africa and Swaziland.
AB  - BACKGROUND: The Australian redclaw crayfish (Cherax quadricarinatus, von
      Martens), is native to Australasia, but has been widely translocated around the
      world due to aquaculture and aquarium trade. Mostly as a result of escape from
      aquaculture facilities, this species has established extralimital populations in
      Australia and alien populations in Europe, Asia, Central America and Africa. In
      South Africa, C. quadricarinatus was first sampled from the wild in 2002 in the
      Komati River, following its escape from an aquaculture facility in Swaziland, but
      data on the current status of its populations are not available. METHODS: To
      establish a better understanding of its distribution, rate of spread and
      population status, we surveyed a total of 46 sites in various river systems in
      South Africa and Swaziland. Surveys were performed between September 2015 and
      August 2016 and involved visual observations and the use of collapsible crayfish
      traps. RESULTS: Cherax quadricarinatus is now present in the Komati, Lomati,
      Mbuluzi, Mlawula and Usutu rivers, and it was also detected in several off
      channel irrigation impoundments. Where present, it was generally abundant, with
      populations having multiple size cohorts and containing ovigerous females. In the
      Komati River, it has spread more than 112 km downstream of the initial
      introduction point and 33 km upstream of a tributary, resulting in a mean spread
      rate of 8 km year-1 downstream and 4.7 km year-1 upstream. In Swaziland,
      estimated downstream spread rate might reach 14.6 km year-1. Individuals were
      generally larger and heavier closer to the introduction site, which might be
      linked to juvenile dispersal. DISCUSSION: These findings demonstrate that C.
      quadricarinatus is established in South Africa and Swaziland and that the species
      has spread, not only within the river where it was first introduced, but also
      between rivers. Considering the strong impacts that alien crayfish usually have
      on invaded ecosystems, assessments of its potential impacts on native freshwater
      biota and an evaluation of possible control measures are, therefore, urgent
      requirements.

PMID- 28439455
TI  - The evolution of logic circuits for the purpose of protein contact map
      prediction.
AB  - Predicting protein structure from sequence remains a major open problem in
      protein biochemistry. One component of predicting complete structures is the
      prediction of inter-residue contact patterns (contact maps). Here, we discuss
      protein contact map prediction by machine learning. We describe a novel method
      for contact map prediction that uses the evolution of logic circuits. These logic
      circuits operate on feature data and output whether or not two amino acids in a
      protein are in contact or not. We show that such a method is feasible, and in
      addition that evolution allows the logic circuits to be trained on the dataset in
      an unbiased manner so that it can be used in both contact map prediction and the
      selection of relevant features in a dataset.

PMID- 28439456
TI  - Metformin ameliorates insulitis in STZ-induced diabetic mice.
AB  - BACKGROUND & AIMS: Metformin is currently the most widely used first-line
      hypoglycemic agent for diabetes mellitus. Besides glucose-lowering action, there
      is increasingly interest in the potential anti-inflammatory action of this drug.
      In the present study, we investigated the actions of metformin on experimental
      insulitis using STZ-induced diabetic mice. METHODS: Mice with acute diabetes
      induced by STZ were administered metformin by gavage. Changes of blood glucose
      and body weight, and the daily amount of food and water intake were measured.
      Pancreatic tissues were collected for histologic analyses. Pathological
      assessment and immunohistochemistry analysis were used to determine the effect of
      metformin on insulitis. Inflammatory cytokines in the pancreas and insulin levels
      were measured through ELISA analysis. RESULTS: Metformin significantly reduced
      blood glucose levels and improved aberrant water intake behavior in experimental
      diabetic mice. No significant differences were observed in terms of body weight
      and food intake behavior in metformin-treated animals. In the STZ-induced model
      of diabetes, we found the appearance of pronounced insulitis. However, metformin
      administration reduced the severity of insulitis assessed by blind pathological
      scoring. In addition, metformin treatment improved insulin levels in experimental
      diabetic mice. ELISA assay revealed decreased levels of inflammatory response
      marker IL-1beta and TNF-alpha in the pancreatic tissues following metformin
      treatment. CONCLUSION: Metformin attenuated insulitis in the STZ-induced mice
      model of diabetes. This islet-protective effect might be partly correlated with
      the anti-inflammatory action of metformin.

PMID- 28439457
TI  - Pollinator diversity and reproductive success of Epipactis helleborine (L.)
      Crantz (Orchidaceae) in anthropogenic and natural habitats.
AB  - BACKGROUND: Epipactis helleborine is an Eurasian orchid species which prefers
      woodland environments but it may also spontaneously and successfully colonise
      human-made artificial and disturbed habitats such as roadsides, town parks and
      gardens. It is suggested that orchids colonising anthropogenic habitats are
      characterised by a specific set of features (e.g., large plant size, fast flower
      production). However, as it is not well known how pollinator diversity and
      reproductive success of E. helleborine differs in populations in anthropogenic
      habitats compared to populations from natural habitats, we wanted to compare
      pollinator diversity and reproductive success of this orchid species between
      natural and anthropogenic habitat types. METHODS: Pollination biology,
      reproductive success and autogamy in populations of E. helleborine from
      anthropogenic (roadside) and natural (forest) habitats were compared. Eight
      populations (four natural and four human-disturbed ones) in two seasons were
      studied according to height of plants, length of inflorescences, as well as
      numbers of juvenile shoots, flowering shoots, flowers, and fruits. The number and
      diversity of insect pollinators were studied in one natural and two human
      disturbed populations. RESULTS: Reproductive success (the ratio of the number of
      flowers to the number of fruits) in the populations from anthropogenic habitats
      was significantly higher than in the natural habitats. Moreover, plants from
      anthropogenic habitats were larger than those from natural ones. In both types of
      populations, the main insect pollinators were Syrphidae, Culicidae, Vespidae,
      Apidae and Formicidae. With respect to the type of pollinators' mouth-parts,
      chewing (39%), sponging (34%) and chewing-sucking (20%) pollinators prevailed in
      anthropogenic habitats. In natural habitats, pollinators with sponging (55%) and
      chewing mouth-parts (32%) dominated, while chewing-sucking and piercing-sucking
      insects accounted for 9% and 4% respectively. DISCUSSION: We suggest that higher
      reproductive success of E. helleborine in the populations from anthropogenic
      habitats than in the populations from natural habitats may result from a higher
      number of visits by pollinators and their greater species diversity, but also
      from the larger size of plants growing in such habitats. Moreover, our data
      clearly show that E. helleborine is an opportunistic species with respect to
      pollinators, with a wide spectrum of pollinating insects. Summarising, E.
      helleborine is a rare example of orchid species whose current range is not
      declining. Its ability to make use of anthropogenically altered habitats has
      allowed its significant spatial range expansion, and even successful colonisation
      of North America.

PMID- 28439459
TI  - Preliminary observations on the age and growth of dog snapper (Lutjanus jocu) and
      mahogany snapper (Lutjanus mahogoni) from the Southeastern U.S.
AB  - Dog snapper (Lutjanus jocu Bloch and Schneider 1801) and mahogany snapper
      (Lutjanus mahogoni Cuvier 1828) are infrequently caught snappers in the
      southeastern U.S. primarily occurring off of southern Florida. The species were
      opportunistically sampled from commercial and recreational fisheries in the
      southeastern U.S. from 1979 to 2015. Fish were aged (56 dog snapper and 54
      mahogany snapper) by counting opaque zones on sectioned sagittal otoliths.
      Otoliths of both species were easily interpretable and agreement between readers
      was acceptable. Analysis of otolith edge-type revealed that annuli formed between
      May and July on both species. Dog snapper ranged from 200-837 mm total length
      (TL) and ages 2-33, while mahogany snapper ranged from 270-416 mm TL and ages 2
      18. The Von Bertalanffy growth equations were Lt  = 746(1-e(-0.20(t-0.32))) and
      Lt  = 334(1-e(0.31(t+1.19))) for dog snapper and mahogany snapper, respectively.
      The weight-length relations were W = 1.31 * 10-5L3.03(n = 78, r2 = 0.99) and W =
      5.40 * 10-6L3.15(n = 79, r2 = 0.79) for dog snapper and mahogany snapper,
      respectively, where W = whole weight in grams.

PMID- 28439458
TI  - The genomic sequence of Exiguobacterium chiriqhucha str. N139 reveals a species
      that thrives in cold waters and extreme environmental conditions.
AB  - We report the genome sequence of Exiguobacterium chiriqhucha str. N139, isolated
      from a high-altitude Andean lake. Comparative genomic analyses of the
      Exiguobacterium genomes available suggest that our strain belongs to the same
      species as the previously reported E. pavilionensis str. RW-2 and Exiguobacterium
      str. GIC 31. We describe this species and propose the chiriqhucha name to group
      them. 'Chiri qhucha' in Quechua means 'cold lake', which is a common origin of
      these three cosmopolitan Exiguobacteria. The 2,952,588-bp E. chiriqhucha str.
      N139 genome contains one chromosome and three megaplasmids. The genome analysis
      of the Andean strain suggests the presence of enzymes that confer E. chiriqhucha
      str. N139 the ability to grow under multiple environmental extreme conditions,
      including high concentrations of different metals, high ultraviolet B radiation,
      scavenging for phosphorous and coping with high salinity. Moreover, the
      regulation of its tryptophan biosynthesis suggests that novel pathways remain to
      be discovered, and that these pathways might be fundamental in the amino acid
      metabolism of the microbial community from Laguna Negra, Argentina.

PMID- 28439460
TI  - Novel polymeric micelles for insect pest control: encapsulation of essential oil
      monoterpenes inside a triblock copolymer shell for head lice control.
AB  - BACKGROUND: Essential oil components (EOCs) are molecules with interesting
      application in pest control, these have been evaluated against different insect
      pest from more than 100 years, but their practical use is rather limited. Thus,
      the enhancement of their bioavailability and manageability due to their
      dispersion in water can open new perspective for the preparation of formulations
      for the control of insect pest. In this work, we studied the encapsulation of
      different monoterpenes in a poloxamer shell in order to prepare aqueous
      formulations that can be used for the development of platforms used in pest
      control. METHODS: Micellar systems containing a 5 wt% of poloxamer 407 and 1.25
      wt% of the different monoterpenes were prepared. Dynamic Light Scattering (DLS)
      experiments were carried out to characterize the dispersion of the EOCs in water.
      The pediculicidal activity of these micellar systems was tested on head lice
      using an ex vivo immersion test. RESULTS: The poloxamers allowed the dispersion
      of EOCs in water due to their encapsulation inside the hydrophobic core of the
      copolymer micelles. From this study, we concluded that it is possible to make
      stable micellar systems containing water (>90 wt%), 1.25 wt% of different
      monoterpenes and a highly safe polymer (5wt% Poloxamer 407). These formulations
      were effective against head lice with mortality ranging from 30 to 60%, being the
      most effective emulsions those containing linalool, 1,8-cineole, alpha-terpineol,
      thymol, eugenol, geraniol and nonyl alcohol which lead to mortalities above 50%.
      DISCUSSION: Since these systems showed good pediculicidal activity and high
      physicochemical stability, they could be a new route for the green fabrication of
      biocompatible and biosustainable insecticide formulations.

PMID- 28439461
TI  - Quantitative assessment of fibroblast growth factor receptor 1 expression in
      neurons and glia.
AB  - BACKGROUND: Fibroblast growth factors (FGFs) and their receptors (FGFRs) have
      numerous functions in the developing and adult central nervous system (CNS). For
      example, the FGFR1 receptor is important for proliferation and fate specification
      of radial glial cells in the cortex and hippocampus, oligodendrocyte
      proliferation and regeneration, midline glia morphology and soma translocation,
      Bergmann glia morphology, and cerebellar morphogenesis. In addition, FGFR1
      signaling in astrocytes is required for postnatal maturation of interneurons
      expressing parvalbumin (PV). FGFR1 is implicated in synapse formation in the
      hippocampus, and alterations in the expression of Fgfr1 and its ligand, Fgf2
      accompany major depression. Understanding which cell types express Fgfr1 during
      development may elucidate its roles in normal development of the brain as well as
      illuminate possible causes of certain neuropsychiatric disorders. METHODS: Here,
      we used a BAC transgenic reporter line to trace Fgfr1 expression in the
      developing postnatal murine CNS. The specific transgenic line employed was
      created by the GENSAT project, tgFGFR1-EGFPGP338Gsat, and includes a gene
      encoding enhanced green fluorescent protein (EGFP) under the regulation of the
      Fgfr1 promoter, to trace Fgfr1 expression in the developing CNS. Unbiased
      stereological counts were performed for several cell types in the cortex and
      hippocampus. RESULTS: This model reveals that Fgfr1 is primarily expressed in
      glial cells, in both astrocytes and oligodendrocytes, along with some neurons.
      Dual labeling experiments indicate that the proportion of GFP+ (Fgfr1+) cells
      that are also GFAP+ increases from postnatal day 7 (P7) to 1 month, illuminating
      dynamic changes in Fgfr1 expression during postnatal development of the cortex.
      In postnatal neurogenic areas, GFP expression was also observed in SOX2,
      doublecortin (DCX), and brain lipid-binding protein (BLBP) expressing cells.
      Fgfr1 is also highly expressed in DCX positive cells of the dentate gyrus (DG),
      but not in the rostral migratory stream. Fgfr1 driven GFP was also observed in
      tanycytes and GFAP+ cells of the hypothalamus, as well as in Bergmann glia and
      astrocytes of the cerebellum. CONCLUSIONS: The tgFGFR1-EGFPGP338Gsat mouse model
      expresses GFP that is congruent with known functions of FGFR1, including
      hippocampal development, glial cell development, and stem cell proliferation.
      Understanding which cell types express Fgfr1 may elucidate its role in
      neuropsychiatric disorders and brain development.

PMID- 28439462
TI  - Microanatomy and paleohistology of the intercentra of North American
      metoposaurids from the Upper Triassic of Petrified Forest National Park (Arizona,
      USA) with implications for the taxonomy and ontogeny of the group.
AB  - Metoposaurids are temnospondyl amphibians that are commonly recovered from the
      Chinle Formation deposits of North America. Two species, Koskinonodon perfectus
      and Apachesaurus gregorii, are known from Petrified Forest National Park (PEFO),
      AZ. Small, elongate intercentra are the single diagnostic postcranial
      characteristic of the smaller A. gregorii. However, a poor understanding of the
      earliest life stages of Koskinonodon perfectus and other large metoposaurids
      makes it unclear whether the proportions of the intercentra are a diagnostic
      feature for species discrimination or whether they are influenced by ontogeny.
      Previous work on metoposaurid intercentra has shown that ontogenetic information
      can be extrapolated from histological analyses. Here, we perform an analysis of
      the microanatomy and the histology of metoposaurid intercentra from PEFO to
      determine their ontogenetic maturity and in turn whether elongate intercentra are
      a reliable taxonomic feature for distinguishing North American metoposaurids. Our
      findings suggest that the elongate intercentra are the result of ontogenetic
      variation within a single large-bodied metoposaurid taxon rather than
      interspecific variation between two metoposaurids of vastly different adult
      sizes. These findings have significant implications for the taxonomy of North
      American metoposaurids and subsequently for interpretations of the Chinle Basin
      paleoenvironment. Furthermore, this study provides the first histological
      characterization of North American metoposaurid intercentra, thereby improving
      the understanding of vertebral ontogeny within Metoposauridae and offering new
      insights into the ecology of large metoposaurids.

PMID- 28439463
TI  - Molecular assessment of the fecal microbiota in healthy cats and dogs before and
      during supplementation with fructo-oligosaccharides (FOS) and inulin using high
      throughput 454-pyrosequencing.
AB  - Prebiotics are selectively fermentable dietary compounds that result in changes
      in the composition and/or activity of the intestinal microbiota, thus conferring
      benefits upon host health. In veterinary medicine, commercially available
      products containing prebiotics have not been well studied with regard to the
      changes they trigger on the composition of the gut microbiota. This study
      evaluated the effect of a commercially available nutraceutical containing fructo
      oligosaccharides (FOS) and inulin on the fecal microbiota of healthy cats and
      dogs when administered for 16 days. Fecal samples were collected at two time
      points before and at two time points during prebiotic administration. Total
      genomic DNA was obtained from fecal samples and 454-pyrosequencing was used for
      16S rRNA gene bacterial profiling. The linear discriminant analysis (LDA) effect
      size (LEfSe) method was used for detecting bacterial taxa that may respond (i.e.,
      increase or decrease in its relative abundance) to prebiotic administration.
      Prebiotic administration was associated with a good acceptance and no side
      effects (e.g., diarrhea) were reported by the owners. A low dose of prebiotics
      (50 mL total regardless of body weight with the end product containing 0.45% of
      prebiotics) revealed a lower abundance of Gammaproteobacteria and a higher
      abundance of Veillonellaceae during prebiotic administration in cats, while
      Staphylococcaceae showed a higher abundance during prebiotic administration in
      dogs. These differences were not sufficient to separate bacterial communities as
      shown by analysis of weighted UniFrac distance metrics. A predictive approach of
      the fecal bacterial metagenome using Phylogenetic Investigation of Communities by
      Reconstruction of Unobserved States (PICRUSt) also did not reveal differences
      between the period before and during prebiotic administration. A second trial
      using a higher dose of prebiotics (3.2 mL/kg body weight with the end product
      containing 3.1% of prebiotics) was tested in dogs and revealed a lower abundance
      of Dorea (family Clostridiaceae) and a higher abundance of Megamonas and other
      (unknown) members of Veillonellaceae during prebiotic administration. Again,
      these changes were not sufficient to separate bacterial communities or predicted
      metabolic profiles according to treatment. A closer analysis of bacterial
      communities at all time-points revealed highly individualized patterns of
      variation. This study shows a high interindividual variation of fecal bacterial
      communities from pet cats and dogs, that these communities are relatively stable
      over time, and that some of this variation can be attributable to prebiotic
      administration, a phenomenon that may be affected by the amount of the prebiotic
      administered in the formulation. This study also provides insights into the
      response of gut bacterial communities in pet cats and dogs during administration
      of commercially available products containing prebiotics. More studies are needed
      to explore potentially beneficial effects on host health beyond changes in
      bacterial communities.

PMID- 28439464
TI  - Null alleles are ubiquitous at microsatellite loci in the Wedge Clam (Donax
      trunculus).
AB  - Recent studies have reported an unusually high frequency of nonamplifying alleles
      at microsatellite loci in bivalves. Null alleles have been associated with
      heterozygous deficits in many studies. While several studies have tested for its
      presence using different analytical tools, few have empirically tested for its
      consequences in estimating population structure and differentiation. We
      characterised 16 newly developed microsatellite loci and show that null alleles
      are ubiquitous in the wedge clam, Donax trunculus. We carried out several tests
      to demonstrate that the large heterozygous deficits observed in the newly
      characterised loci were most likely due to null alleles. We tested the robustness
      of microsatellite genotyping for population assignment by showing that well
      recognised biogeographic regions of the south Atlantic and south Mediterranean
      coast of Spain harbour genetically different populations.

PMID- 28439465
TI  - Single exponential decay waveform; a synergistic combination of electroporation
      and electrolysis (E2) for tissue ablation.
AB  - BACKGROUND: Electrolytic ablation and electroporation based ablation are
      minimally invasive, non-thermal surgical technologies that employ electrical
      currents and electric fields to ablate undesirable cells in a volume of tissue.
      In this study, we explore the attributes of a new tissue ablation technology that
      simultaneously delivers a synergistic combination of electroporation and
      electrolysis (E2). METHOD: A new device that delivers a controlled dose of
      electroporation field and electrolysis currents in the form of a single
      exponential decay waveform (EDW) was applied to the pig liver, and the effect of
      various parameters on the extent of tissue ablation was examined with histology.
      RESULTS: Histological analysis shows that E2 delivered as EDW can produce tissue
      ablation in volumes of clinical significance, using electrical and temporal
      parameters which, if used in electroporation or electrolysis separately, cannot
      ablate the tissue. DISCUSSION: The E2 combination has advantages over the three
      basic technologies of non-thermal ablation: electrolytic ablation,
      electrochemical ablation (reversible electroporation with injection of drugs) and
      irreversible electroporation. E2 ablates clinically relevant volumes of tissue in
      a shorter period of time than electrolysis and electroporation, without the need
      to inject drugs as in reversible electroporation or use paralyzing anesthesia as
      in irreversible electroporation.

PMID- 28439466
TI  - Arrival and diversification of mabuyine skinks (Squamata: Scincidae) in the
      Neotropics based on a fossil-calibrated timetree.
AB  - BACKGROUND: The evolution of South American Mabuyinae skinks holds significant
      biogeographic interest because its sister lineage is distributed across the
      African continent and adjacent islands. Moreover, at least one insular species,
      Trachylepis atlantica, has independently reached the New World through
      transoceanic dispersal. To clarify the evolutionary history of both Neotropical
      lineages, this study aimed to infer an updated timescale using the largest
      species and gene sampling dataset ever assembled for this group. By extending the
      analysis to the Scincidae family, we could employ fossil information to estimate
      mabuyinae divergence times and carried out a formal statistical biogeography
      analysis. To unveil macroevolutionary patterns, we also inferred diversification
      rates for this lineage and evaluated whether the colonization of South American
      continent significantly altered the mode of Mabuyinae evolution. METHODS: A time
      calibrated phylogeny was inferred under the Bayesian framework employing fossil
      information. This timetree was used to (i) evaluate the historical biogeography
      of mabuiyines using the statistical approach implemented in BioGeoBEARS; (ii)
      estimate macroevolutionary diversification rates of the South American Mabuyinae
      lineages and the patterns of evolution of selected traits, namely, the mode of
      reproduction, body mass and snout-vent length; (iii) test the hypothesis of
      differential macroevolutionary patterns in South American lineages in BAMM and
      GeoSSE; and (iv) re-evaluate the ancestral state of the mode of reproduction of
      mabuyines. RESULTS: Our results corroborated the hypothesis that the occupation
      of the South American continent by Mabuyinae consisted of two independent
      dispersion events that occurred between the Oligocene and the Miocene. We found
      significant differences in speciation rates between the New World and the
      remaining Mabuyinae clades only in GeoSSE. The influence of phenotypic traits on
      diversification rates was not supported by any method. Ancestral state
      reconstruction suggested that the ancestor of South American mabuyine was likely
      viviparous. DISCUSSION: Our analyses further corroborated the existence of a
      transoceanic connection between Africa and South America in the Eocene/Oligocene
      period (Atlantogea). Following colonization of the isolated South America and
      subsequent dispersal through the continent by the ancestral mabuyine stock, we
      detected no difference in macroevolutionary regimes of New World clades. This
      finding argued against the ecological opportunity model as an explanation for the
      diversity of living mabuyines.

PMID- 28439467
TI  - Floral pathway integrator gene expression mediates gradual transmission of
      environmental and endogenous cues to flowering time.
AB  - The appropriate timing of flowering is crucial for the reproductive success of
      plants. Hence, intricate genetic networks integrate various environmental and
      endogenous cues such as temperature or hormonal statues. These signals integrate
      into a network of floral pathway integrator genes. At a quantitative level, it is
      currently unclear how the impact of genetic variation in signaling pathways on
      flowering time is mediated by floral pathway integrator genes. Here, using
      datasets available from literature, we connect Arabidopsis thaliana flowering
      time in genetic backgrounds varying in upstream signalling components with the
      expression levels of floral pathway integrator genes in these genetic
      backgrounds. Our modelling results indicate that flowering time depends in a
      quite linear way on expression levels of floral pathway integrator genes. This
      gradual, proportional response of flowering time to upstream changes enables a
      gradual adaptation to changing environmental factors such as temperature and
      light.

PMID- 28439469
TI  - Migratory orientation in a narrow avian hybrid zone.
AB  - BACKGROUND: Zones of contact between closely related taxa with divergent
      migratory routes, termed migratory divides, have been suggested as areas where
      hybrid offspring may have intermediate and inferior migratory routes, resulting
      in low fitness of hybrids and thereby promoting speciation. In the Rocky
      Mountains of Canada there is a narrow hybrid zone between Audubon's and myrtle
      warblers that is likely maintained by selection against hybrids. Band recoveries
      and isotopic studies indicate that this hybrid zone broadly corresponds to the
      location of a possible migratory divide, with Audubon's warblers migrating south
      southwest and myrtle warblers migrating southeast. We tested a key prediction of
      the migratory divide hypothesis: that genetic background would be predictive of
      migratory orientation among warblers in the center of the hybrid zone. METHODS:
      We recorded fall migratory orientation of wild-caught migrating warblers in the
      center of the hybrid zone as measured by video-based monitoring of migratory
      restlessness in circular orientation chambers. We then tested whether there was a
      relationship between migratory orientation and genetic background, as measured
      using a set of species-specific diagnostic genetic markers. RESULTS: We did not
      detect a significant association between orientation and genetic background.
      There was large variation among individuals in orientation direction. Mean
      orientation was towards the NE, surprising for birds on fall migration, but
      aligned with the mountain valley in which the study took place. CONCLUSIONS: Only
      one other study has directly analyzed migratory orientation among naturally
      produced hybrids in a migratory divide. While the other study showed an
      association between genetic background and orientation, we did not observe such
      an association in yellow-rumped warblers. We discuss possible reasons, including
      the possibility of a lack of a strong migratory divide in this hybrid zone and/or
      methodological limitations that may have prevented accurate measurements of long
      distance migratory orientation.

PMID- 28439468
TI  - A link between central kynurenine metabolism and bone strength in rats with
      chronic kidney disease.
AB  - BACKGROUND: Disturbances in mineral and bone metabolism represent one of the most
      complex complications of chronic kidney disease (CKD). Serotonin, a monoamine
      synthesized from tryptophan, may play a potential role in bone metabolism. Brain
      derived serotonin exerts a positive effect on the bone structure by limiting bone
      resorption and enhancing bone formation. Tryptophan is the precursor not only to
      the serotonin but also and primarily to kynurenine metabolites. The ultimate aim
      of the present study was to determine the association between central kynurenine
      metabolism and biomechanical as well as geometrical properties of bone in the
      experimental model of the early stage of CKD. METHODS: Thirty-three Wistar rats
      were randomly divided into two groups (sham-operated and subtotal nephrectomized
      animals). Three months after surgery, serum samples were obtained for the
      determination of biochemical parameters, bone turnover biomarkers, and kynurenine
      pathway metabolites; tibias were collected for bone biomechanical, bone
      geometrical, and bone mass density analysis; brains were removed and divided into
      five regions for the determination of kynurenine pathway metabolites. RESULTS:
      Subtotal nephrectomized rats presented higher serum concentrations of creatinine,
      urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several
      biomechanical and geometrical parameters were significantly elevated in rats with
      experimentally induced CKD. Subtotal nephrectomized rats presented significantly
      higher kynurenine concentrations and kynurenine/tryptophan ratio and
      significantly lower tryptophan levels in all studied parts of the brain.
      Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum
      correlated positively with the main parameters of bone biomechanics and bone
      geometry. DISCUSSION: In addition to the complex mineral, hormone, and metabolite
      changes, intensified central kynurenine turnover may play an important role in
      the development of bone changes in the course of CKD.

PMID- 28439470
TI  - Mitochondrial diversity in Gonionemus (Trachylina:Hydrozoa) and its implications
      for understanding the origins of clinging jellyfish in the Northwest Atlantic
      Ocean.
AB  - Determining whether a population is introduced or native to a region can be
      challenging due to inadequate taxonomy, the presence of cryptic lineages, and
      poor historical documentation. For taxa with resting stages that bloom
      episodically, determining origin can be especially challenging as an
      environmentally-triggered abrupt appearance of the taxa may be confused with an
      anthropogenic introduction. Here, we assess diversity in mitochondrial cytochrome
      oxidase I sequences obtained from multiple Atlantic and Pacific locations, and
      discuss the implications of our findings for understanding the origin of clinging
      jellyfish Gonionemus in the Northwest Atlantic. Clinging jellyfish are known for
      clinging to seagrasses and seaweeds, and have complex life cycles that include
      resting stages. They are especially notorious as some, although not all,
      populations are associated with severe sting reactions. The worldwide
      distribution of Gonionemus has been aptly called a "zoogeographic puzzle" and our
      results refine rather than resolve the puzzle. We find a relatively deep
      divergence that may indicate cryptic speciation between Gonionemus from the
      Northeast Pacific and Northwest Pacific/Northwest Atlantic. Within the Northwest
      Pacific/Northwest Atlantic clade, we find haplotypes unique to each region. We
      also find one haplotype that is shared between highly toxic Vladivostok-area
      populations and some Northwest Atlantic populations. Our results are consistent
      with multiple scenarios that involve both native and anthropogenic processes. We
      evaluate each scenario and discuss critical directions for future research,
      including improving the resolution of population genetic structure, identifying
      possible lineage admixture, and better characterizing and quantifying the
      toxicity phenotype.

PMID- 28439471
TI  - Exergames for women with fibromyalgia: a randomised controlled trial to evaluate
      the effects on mobility skills, balance and fear of falling.
AB  - BACKGROUND: Exergames are a new form of rehabilitation that combine the
      characteristics of physical exercise and the benefits of non-immersive virtual
      reality (VR). Effects of this novel therapy in women fibromyalgia are still
      unknown. The objective was to evaluate the effects of exergame-based intervention
      on mobility skills, balance and fear of falling in women with fibromyalgia.
      METHODS: This study was a randomized controlled trial with concealed allocation.
      Seventy-six women with fibromyalgia were divided into two groups: the exercise
      group received an eight week intervention based on exergames, while the control
      group continued their usual activities. Mobility skills were evaluated using the
      timed up and go test, while balance was assessed using the functional reach test,
      and the CTSIB protocol. Fear of falling was evaluated on a scale of 0-100 (0, no
      fear; 100, extreme fear). Measurements were performed before and after the
      intervention. A repeated-measures linear mixed model was used to compare the
      effects of the intervention between the two groups. RESULTS: The exercise group
      was significantly quicker than the control group in the timed up and go test (MD,
      -0.71; 95% CI [-1.09-0.32]; p < 0.001). There were also significant improvements
      in functional reach and a reduced fear of falling (MD, 4.34; 95% CI [1.39-7.30];
      p = 0.005 and MD, -9.85; 95% CI [-0.19--0.08]; p = 0.048, respectively).
      DISCUSSION: The improved TUG observed herein was better than the smallest real
      difference. Based on the results on mobility skills, balance and fear of falling,
      exergames may be an effective tool as a therapy for women with fibromyalgia.

PMID- 28439472
TI  - New findings of Pleistocene fossil turtles (Geoemydidae, Kinosternidae and
      Chelydridae) from Santa Elena Province, Ecuador.
AB  - New Pleistocene fossilized turtle remains from five localities of western Ecuador
      (Santa Elena Province) are described here. All these shell (carapace and
      plastron) fossil remains come from the Tablazo Formation and belong to three
      different lineages of cryptodires ("hidden-necked" turtles). The most abundant
      remains belong to geoemydids, attributed here to the genus Rhinoclemmys
      (indeterminate species). Less abundant in occurrence are the kinosternidids,
      attributed to Kinosternon (indeterminate species), and the first fossil record of
      chelydrids, Chelydra(indeterminate species), in the entirety of Central and South
      America.

PMID- 28439473
TI  - The behavioral response of prey fish to predators: the role of predator size.
AB  - Predation is one of the key factors governing patterns in natural systems, and
      adjustments of prey behaviors in response to a predator stimulus can have
      important ecological implications for wild fish. To investigate the effects of
      predators on the behavior of prey fish and to test whether the possible effects
      varied with predator size, black carp (Mylopharyngodon piceus) and snakehead
      (Channa argus) (a size-matched predator treatment with a similar body size to
      prey fish and a larger predator treatment with approximately 2.7 times of the
      body mass of prey fish) were selected to function as prey and predator,
      respectively. Their spontaneous activities were videorecorded in a central
      circular arena surrounded by a ring holding the stimulus fish. The distance
      between prey and predator fish was approximately 200% of the distance between two
      prey fish, which suggested that black carp can distinguish their conspecifics
      from heterospecifics and probably recognize the snakehead as a potential
      predator. The prey fish spent substantially less time moving and exhibited an
      overall shorter total distance of movement after the size-matched or large
      predator was introduced, which possibly occurred due to increased vigilance or
      efforts to reduce the possibility of detection by potential predators. However,
      there was no significant difference in either distance or spontaneous activities
      between two predator treatments. These findings suggested that (1) an anti
      predator strategy in black carp might involve maintaining a safe distance,
      decreasing activity and possibly increased vigilance and that (2) the behaviors
      of prey response to predators were not influenced by their relative size
      difference.

PMID- 28439474
TI  - Digitizing specimens in a small herbarium: A viable workflow for collections
      working with limited resources.
AB  - PREMISE OF THE STUDY: Small herbaria represent a significant portion of herbaria
      in the United States, but many are not digitizing their collections. METHODS: At
      the Arkansas State University Herbarium (STAR), we have created a viable workflow
      to help small herbaria begin the digitization process, including suggestions for
      publishing data on the Internet. We calculated hourly rates of each phase of the
      digitization process. We also mapped accessions at the county level to determine
      geographic strengths in the collection. RESULTS: All 17,678 accessioned flowering
      plant specimens at STAR are imaged, databased in Specify, and available
      electronically on the herbarium's website. Students imaged the specimens at a
      mean rate of 145/h. We found differences in databasing rates between the graduate
      student leading the project (47/h) and undergraduate assistants (25/h). The
      majority of specimens at STAR were collected within the counties neighboring the
      institution. DISCUSSION: With this workflow, we estimate that one person can
      digitize a 20,000-specimen collection in less than 2.5 yr by working only 10
      h/wk. Because STAR is a small herbarium with limited resources, the application
      of the workflow described should assist curators of similar-sized collections as
      they contemplate and undertake the digitization process.

PMID- 28439475
TI  - Transcriptomic resources for an endemic Neotropical plant lineage (Gesneriaceae).
AB  - PREMISE OF THE STUDY: Despite the extensive phenotypic variation that
      characterizes the Gesneriaceae family, there is a lack of genomic resources to
      investigate the molecular basis of their diversity. We developed and compared the
      transcriptomes for two species of the Neotropical lineage of the Gesneriaceae.
      METHODS AND RESULTS: Illumina sequencing and de novo assembly of floral and leaf
      samples were used to generate multigene sequence data for Sinningia eumorpha and
      S. magnifica, two species endemic to the Brazilian Atlantic Forest. A total of
      300 million reads were used to assemble the transcriptomes, with an average of
      92,038 transcripts and 43,506 genes per species. The transcriptomes showed good
      quality metrics, with the presence of all eukaryotic core genes, and an equal
      representation of clusters of orthologous groups (COG) classifications between
      species. The orthologous search produced 8602 groups, with 15-20% of them
      annotated using BLAST tools. DISCUSSION: This study provides the first step
      toward a comprehensive multispecies transcriptome characterization of the
      Gesneriaceae family. These resources are the basis for comparative analyses in
      this species-rich Neotropical plant group; they will also allow the investigation
      of the evolutionary importance of multiple metabolic pathways and phenotypic
      diversity, as well as developmental programs in these nonmodel species.

PMID- 28439476
TI  - Development and characterization of 18 polymorphic SSR markers for Barthea
      barthei (Melastomataceae).
AB  - PREMISE OF THE STUDY: To examine population differentiation, simple sequence
      repeat (SSR) markers were developed in Barthea barthei, a shrub with a disjunct
      distribution in the southern mainland of China and Taiwan. METHODS AND RESULTS:
      We used Illumina HiSeq technology to sequence a genomic library for SSR
      identification. Twenty-seven SSR loci were developed, of which 18 SSR loci were
      polymorphic in three populations composed of two varieties of B. barthei. At the
      population level, the number of alleles ranged from one to seven, and the
      observed and expected heterozygosity varied from 0 to 0.850 and from 0 to 0.809,
      respectively. Higher genetic differentiation between the two populations of B.
      barthei var. barthei (FST = 0.474) was observed relative to the two varieties
      (FST = 0.387 and 0.418, respectively). CONCLUSIONS: These polymorphic SSR markers
      may be useful for understanding phytogeographic history of B. barthei. Lower
      genetic differentiation between the two varieties than between the two
      populations of B. barthei var. barthei suggests that the taxonomic treatment may
      not hold.

PMID- 28439477
TI  - Development and characterization of EST-SSR markers in Stipa breviflora
      (Poaceae).
AB  - PREMISE OF THE STUDY: Stipa breviflora (Poaceae) is one of the dominant species
      of the desert steppe in the eastern Eurasian grasslands. Simple sequence repeat
      (SSR) markers were developed for use in genetic diversity studies of this
      species. METHODS AND RESULTS: A total of 1954 potentially polymorphic loci were
      obtained by comparing transcriptome data of eight different S. breviflora
      individuals. We selected 81 loci to verify polymorphism and 63 loci amplified, of
      which 21 loci exhibited polymorphism. The number of alleles per locus varied from
      two to 24, the observed heterozygosity ranged from 0.083 to 0.958, and the
      expected heterozygosity ranged from 0.396 to 0.738. CONCLUSIONS: These newly
      identified SSR loci can be used for population genetic and landscape genetic
      studies of S. breviflora. In addition, 14 loci also amplified in six related
      Stipa species (S. grandis, S. krylovii, S. bungeana, S. aliena, S. gobica, and S.
      purpurea).

PMID- 28439478
TI  - Development of microsatellite loci in Mediterranean sarsaparilla (Smilax aspera;
      Smilacaceae) using transcriptome data.
AB  - PREMISE OF THE STUDY: Although several microsatellite markers of Smilax aspera
      (Smilacaceae) have been reported in a previous study, due to universality issues
      in cross-population amplification, we have newly developed microsatellite markers
      for S. aspera based on transcriptome data to further investigate gene flow and
      genetic structure of its circum-Mediterranean, East African, and South Asian
      populations. METHODS AND RESULTS: A total of 4854 simple sequence repeat (SSR)
      primer pairs were designed from 99,193 contigs acquired from public transcriptome
      data of S. bona-nox. Forty-six microsatellite loci were selected for further
      genotyping in 12 S. aspera populations. The number of alleles varied from three
      to 28, and 93.5% of the developed microsatellite markers could be cross-amplified
      in least one of three congeneric Smilax species. CONCLUSIONS: The SSR markers
      developed in this study will facilitate further studies on genetic diversity and
      phylogeographic patterns of S. aspera in intercontinental geographical scales.

PMID- 28439479
TI  - Simple sequence repeat markers for kanuka (Kunzea spp.; Myrtaceae) present in New
      Zealand.
AB  - PREMISE OF THE STUDY: We developed simple sequence repeat (SSR) markers to
      facilitate population genetic studies on kanuka (Kunzea spp.; Myrtaceae). METHODS
      AND RESULTS: A shotgun sequencing library was constructed from leaf material of
      K. robusta using a Roche 454 Junior sequencer, and a total of 3174 putative SSR
      regions were identified. Sixteen polymorphic markers were optimized for multiplex
      PCR on 10 endemic New Zealand Kunzea species. Each of these loci cross-amplified
      in all tested species. The amplified di-, tri-, and pentanucleotide repeats
      resulted in eight to 24 alleles per locus for a total of 220 specimens. The mean
      observed and expected heterozygosity per locus ranged from 0.18 to 0.77 and 0.33
      to 0.82, respectively. CONCLUSIONS: The SSR markers we produced are valuable for
      phylogenetic and population studies on all endemic Kunzea spp. and may also be
      useful for studies on closely related Kunzea species from Australia.

PMID- 28439480
TI  - Development of microsatellite markers based on expressed sequence tags in
      Asparagus cochinchinensis (Asparagaceae).
AB  - PREMISE OF THE STUDY: Transcriptome-derived simple sequence repeat (SSR) markers
      were developed in Asparagus cochinchinensis (Asparagaceae). Due to its
      application in traditional medicine, its wild populations are threatened by over
      collection even in protected areas, requiring immediate conservation efforts.
      METHODS AND RESULTS: Based on transcriptome data of A. cochinchinensis, 96 primer
      pairs with two to seven alleles per locus were selected for initial validation;
      of those, 27 primer pairs amplified across all samples, resulting in 15
      polymorphic and 12 monomorphic microsatellite markers. The usefulness of these
      markers was assessed in 60 individuals representing three populations of A.
      cochinchinensis. Observed and expected heterozygosity values ranged from 0.050 to
      0.950 and 0.049 to 0.626, respectively. Cross-species amplification of the 27
      markers was tested in the related species A. rigidulus and A. schoberioides.
      CONCLUSIONS: These polymorphic, transcriptome-derived SSR markers can be used as
      molecular markers to study population genetics and ecological conservation in A.
      cochinchinensis and related taxa.

PMID- 28439481
TI  - Sit-to-Stand Transition Reveals Acute Fall Risk in Activities of Daily Living.
AB  - The focus of this paper was on finding wrist sensor-derived features for
      detecting highly acute fall risk from the sit-to-stand transitions performed in a
      non-ambulatory environment. Furthermore, the influence of the dominant and non
      dominant hand on these features was investigated. A cohort of 174 older subjects
      was monitored for seven consecutive days in their home setting by using inertial
      sensors attached at the wrist. Based on the reported falls during a one-month
      follow-up phase, two groups were defined. Twenty-one time and frequency domain
      features were implemented for the quantitative assessment of extracted sit-to
      stand transitions. The statistical analysis yielded two features that could
      convincingly distinguish fallers from non-fallers for the dominant hand, and six
      for the non-dominant hand. A novel feature, energy of the applied support during
      standing up, showed statistically good performance independently of on which hand
      the sensor node was worn, as well as for the dominant and non-dominant hand
      ([Formula: see text], [Formula: see text], and [Formula: see text],
      respectively). This paper overcomes limitations of clinical tests and shows a
      reliable application of wrist-worn bands in terms of assessment of highly acute
      fall risk. In addition, it reveals the sit-to-stand transition as a potential
      assessment source for the wrist-worn devices in the elderly population. Early
      assessment of the risk of falling in a widely accepted and non-stigmatized manner
      has the ability to bring crucial changes in fall prevention strategies, reducing
      the number of falls and the fall rate.

PMID- 28439482
TI  - Association of Non-alcoholic Fatty Liver Disease with Conduction Defects on
      Electrocardiogram.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver
      disease in developed countries. The association of NAFLD with conduction defects
      is unknown. The aim of our study was to find whether an association exists
      between conduction defects and NAFLD. METHODS: This is a case-control
      retrospective study of 700 patients admitted to Orange Park Medical Center,
      Orange Park, Florida from 2009 to 2015. Patients with a history of alcohol use,
      congenital heart disease, infiltrative malignancy, and myocarditis were excluded
      from the study. NAFLD was diagnosed by detection of hepatic steatosis on
      abdominal ultrasound or computerized tomography (CT) scan. Electrocardiograms
      (EKGs) were performed on all 700 patients and were interpreted by a cardiologist.
      Univariate logistic regression was used to assess the association between NAFLD
      and the variables of demographics, clinical characteristics, medicine use, EKG
      changes, and conduction defects, while multivariate logistic regression with
      backward elimination method was performed to determine if NAFLD is one of the
      most important risk factors for conduction defects. RESULTS: The study population
      included 408 patients with NAFLD and 292 patients with No-NAFLD. A total of 155
      conduction defects occurred in 140 patients; conduction defects included 25.7%
      (36) patients with first degree block, 2.1% (three) patients with Mobitz type 1
      block, 41.4% (58) patients with right bundle branch block (RBBB), 17.9% (25)
      patients with left bundle branch block (LBBB), 11.4% (16) patients with
      bifascicular block, and 12.1% (17) patients with nonspecific intraventricular
      block. Multivariate logistic regression with backward elimination method
      identified six risk factors for conduction defects; these included NAFLD (odds
      ratio (OR) 2.38; 95% confidence interval (CI) 1.51-3.73, p<0.0001), hypertrophy
      (OR 2.52; 95% CI 1.57-4.05, p=0.0001), congestive heart failure (CHF) (OR 3.05;
      95%CI 1.46-6.38, p=0.0031), male sex (OR 1.79; 95%CI 1.19-2.69, p=0.0051),
      diabetes mellitus (OR 1.63; 95% CI 1.08-2.47, p=0.02), and age (OR 1.04; 95% CI
      1.02-1.06, p<0.0001). CONCLUSION: NAFLD is associated with conduction defects.
      Prospective randomized trials are needed to demonstrate that NAFLD causes
      conduction defects.

PMID- 28439483
TI  - Whipple's Disease Manifested as Recurrent Ascites.
AB  - Whipple's disease commonly presents as chronic diarrhea and abdominal pain.
      Ascites is an uncommon presentation of Whipple's disease. Here, we report a rare
      case of a 47-year-old male who presented with diarrhea and abdominal distention
      for three months. The physical examination was significant for ascites. Serum
      albumin was low and serum-to-ascites albumin gradient was < 1.1 g/dl. This
      suggested that ascites was less likely to be present due to portal hypertension.
      Enteroscopy showed erythematous duodenum and jejunum; biopsy was suggestive of
      periodic acid-Schiff stain (PAS) positive macrophages consistent with Whipple's
      disease. During the hospital course, the patient improved with intravenous (IV)
      ceftriaxone.

PMID- 28439484
TI  - Gastroschisis Simulation Model: Pre-surgical Management Technical Report.
AB  - This technical report describes the creation of a gastroschisis model for a
      newborn. This is a simple, low-cost task trainer that provides the opportunity
      for Neonatology providers, including fellows, residents, nurse practitioners,
      physician assistants, and nurses, to practice the management of a baby with
      gastroschisis after birth and prior to surgery. Included is a suggested checklist
      with which the model can be employed. The details can be modified to suit
      different learning objectives.

PMID- 28439485
TI  - Treatment of Atypical Hemolytic-Uremic Syndrome in the Era of Eculizumab.
AB  - Hemolytic-uremic syndrome (HUS) is the triad of microangiopathic hemolytic anemia
      (MAHA), thrombocytopenia, and acute kidney injury (AKI); the main cause of multi
      organ failure is related to thrombotic microangiopathy (TMA). Atypical HUS (aHUS)
      is a disease of uncontrolled complement activation associated with a high
      mortality rate and most cases progress to end-stage renal disease. About 50% of
      patients with this syndrome carry mutations in genes that encode complement
      proteins. Also, aHUS constitutes an over-activation of the complement pathway
      which is either inherited, acquired, or both. This results in TMA. Plasma
      infusions or exchange should be performed daily until the platelet count, lactate
      dehydrogenase (LDH), and hemoglobin levels are substantially improved, or until
      an alternate treatment strategy has been decided upon. Eculizumab (a terminal
      complement inhibitor approved in 2011 for treating aHUS) treatment should begin
      immediately when the diagnosis is confirmed. There is limited evidence on the
      duration of the treatment despite significant clinical interest in investigating
      this aspect. Therefore, it is crucial to conduct further analysis on the possible
      dose and time adjustments.

PMID- 28439486
TI  - Bilateral Simultaneous Revision Total Knee Arthroplasty as a Single Staged
      Procedure: A Case Report and Review of Literature.
AB  - Bilateral revision total knee arthroplasty (TKA) is a surgical procedure, which
      is rarely done simultaneously as it is a difficult surgery and the safety of
      simultaneous bilateral single stage surgery remains unknown. We report a case of
      a 67-year-old woman who presented to us with bilateral painful and unstable TKA
      (right > left) of six months duration. The primary bilateral TKA were done 14
      years ago. Bilateral simultaneous revision TKA was performed, using cemented,
      constrained, long-stem prostheses. The intraoperative and postoperative periods
      remained uneventful. At last follow-up at four years, she had a pain-free range
      of motion of up to 0-115 degrees , and the patient had returned to the activities
      of daily living. She had stable knees with good function and no evidence of
      loosening or wear.

PMID- 28439487
TI  - Modified rice bran hemicellulose inhibits vascular endothelial growth factor
      induced angiogenesis in vitro via VEGFR2 and its downstream signaling pathways.
AB  - Angiogenesis is implicated in diverse pathological conditions such as cancer,
      rheumatoid arthritis, psoriasis, atherosclerosis, and retinal neovascularization.
      In the present study, we investigated the effects of modified rice bran
      hemicellulose (MRBH), a water-soluble hemicellulose preparation from rice bran
      treated with shiitake enzymes, on vascular endothelial growth factor (VEGF)
      induced angiogenesis in vitro and its mechanism. We found that MRBH significantly
      inhibited VEGF-induced tube formation in human umbilical vein endothelial cells
      (HUVECs) co-cultured with human dermal fibroblasts. We also observed that MRBH
      dose-dependently suppressed the VEGF-induced proliferation and migration of
      HUVECs. Furthermore, examination of the anti-angiogenic mechanism indicated that
      MRBH reduced not only VEGF-induced activation of VEGF receptor 2 but also of the
      downstream signaling proteins Akt, extracellular signal-regulated protein kinase
      1/2, and p38 mitogen-activated protein kinase. These findings suggest that MRBH
      has in vitro anti-angiogenic effects that are partially mediated through the
      inhibition of VEGF signaling.

PMID- 28439488
TI  - Randomized, double-blind, placebo-controlled, parallel-group study of the effect
      of Lactobacillus paracasei K71 intake on salivary release of secretory
      immunoglobulin A.
AB  - Lactobacillus paracasei K71 was shown to be effective in alleviating the severity
      of atopic dermatitis in a randomized controlled trial, and a preliminary open
      label trial suggested that strain K71 intake enhanced secretory immunoglobulin A
      (sIgA) release in the saliva. This study investigated the effect of K71 on sIgA
      release in a randomized, double-blind, placebo-controlled, parallel-group trial.
      The trial included 62 Japanese subjects aged 20-64 years with relatively low
      rates of salivary sIgA release. Subjects (n=31 in each group) were randomly given
      a tablet containing 100 mg (approximately 2 * 1011 bacteria) of K71 or a placebo
      tablet daily for 12 weeks. After eliminating data for eight subjects (four in
      each group) who met the exclusion criteria for efficacy analysis, data for 54
      subjects were analyzed. The change in the rate of salivary sIgA release 8 weeks
      after initiation of the study compared with baseline was significantly higher in
      the K71 tablet group (105.5 +/- 119.0 ug/min) than in the placebo group (52.7 +/-
      62.6 ug/min; p=0.047). There were no adverse events associated with intake of
      tablets containing K71. The safety of intake of L. paracasei K71 was also
      confirmed in an independent open-label trial with 20 healthy subjects who
      consumed excessive amounts of K71-containing food. L. paracasei K71 intake may
      therefore have some benefits in promoting mucosal immune function.

PMID- 28439489
TI  - Detection and analysis of Lactobacillus paracasei penicillin-binding proteins
      revealed the presence of cholate-sensitive penicillin-binding protein 3 and an
      elongated cell shape in a cholate-sensitive strain.
AB  - Penicillin-binding proteins (PBPs) are responsible for peptidoglycan synthesis.
      By using biotinylated ampicillin, we detected PBPs of Lactobacillus paracasei
      strains. Ten PBPs were identified, 7 of which had apparent molecular sizes
      similar to those of Escherichia coli. In the presence of cholate, strain NRIC
      0625 showed an elongated shape, and its putative PBP3 showed cholate-sensitive
      penicillin-binding activity. Furthermore, this strain was highly sensitive to
      cefalexin, which is known to inhibit cell division by inactivating PBP3. These
      results suggest that the septum synthetase PBP3 of lactic acid bacteria can be
      one of the targets of intestinal bile acid.

PMID- 28439490
TI  - Watch and wait policy in advanced neuroendocrine tumors: What does it mean?
AB  - Neuroendocrine neoplasms (NENs) are a group of rare and heterogeneous
      malignancies, which can develop in various organs. The clinical course of NENs is
      quite heterogeneous, with different spontaneous growth rates after diagnosis, and
      different degrees of sensitivity to the same therapy even when they have similar
      characteristics. Watch and wait (W and W), is a term coined to indicate
      observation being conducted to assess the evolution of the tumor without
      administering any anti-tumor therapy. It has been applied to NENs since in
      extremely rare cases they tend to remain stable for a long time. Although W and W
      has been reported in several guidelines and recommendations it has never been
      validated, nor has it been specifically investigated. Furthermore it is not
      standardized. Therefore its application in clinical practice can differ in terms
      of tumor status assessment, type and timing of imaging or other exams utilized.
      In conclusion, while undertaking W and W to delay the first-line therapy by some
      weeks may be justified in good performance asymptomatic patients with low-grade
      NENs in order to usefully characterize the disease and patient and thereby choose
      the best therapy and therapeutic strategy, it seems to be far more difficult to
      justify W and W with the intent of avoiding an anti-tumor treatment. It should be
      considered that not only do NENs tend to grow even when they have very favorable
      biological characteristics but also that the alternative to W and W is most
      commonly a low toxic and effective treatment with somatostatin analogs.

PMID- 28439491
TI  - Translating new data to the daily practice in second line treatment of renal cell
      carcinoma: The role of tumor growth rate.
AB  - The therapeutic options for patients with metastatic renal cell carcinoma (mRCC)
      have completely changed during the last ten years. With the sequential use of
      targeted therapies, median overall survival has increased in daily practice and
      now it is not uncommon to see patients surviving kidney cancer for more than four
      to five years. Once treatment fails with the first line targeted therapy, head to
      head comparisons have shown that cabozantinib, nivolumab and the combination of
      lenvatinib plus everolimus are more effective than everolimus alone and that
      axitinib is more active than sorafenib. Unfortunately, it is very unlikely that
      we will ever have prospective data comparing the activity of axitinib,
      cabozantinib, lenvatinib or nivolumab. It is frustrating to observe the lack of
      biomarkers that we have in this field, thus there is no firm recommendation about
      the optimal sequence of treatment in the second line. In the absence of reliable
      biomarkers, there are several clinical endpoints that can help physicians to make
      decisions for an individual patient, such as the tumor burden, the expected
      response rate and the time to achieve the response to each agent, the prior
      response to the agent administered, the toxicity profile of the different
      compounds and patient preference. Here, we propose the introduction of the tumor
      growth rate (TGR) during first-line treatment as a new tool to be used to select
      the second line strategy in mRCC. The rapidness of TGR before the onset of the
      treatment reflects the variability between patients in terms of tumor growth
      kinetics and it could be a surrogate marker of tumor aggressiveness that may
      guide treatment decisions.

PMID- 28439492
TI  - Leptin signaling and cancer chemoresistance: Perspectives.
AB  - Obesity is a major health problem and currently is endemic around the world.
      Obesity is a risk factor for several different types of cancer, significantly
      promoting cancer incidence, progression, poor prognosis and resistance to anti
      cancer therapies. The study of this resistance is critical as development of
      chemoresistance is a serious drawback for the successful and effective drug-based
      treatments of cancer. There is increasing evidence that augmented adiposity can
      impact on chemotherapeutic treatment of cancer and the development of resistance
      to these treatments, particularly through one of its signature mediators, the
      adipokine leptin. Leptin is a pro-inflammatory, pro-angiogenic and pro
      tumorigenic adipokine that has been implicated in many cancers promoting
      processes such as angiogenesis, metastasis, tumorigenesis and survival/resistance
      to apoptosis. Several possible mechanisms that could potentially be developed by
      cancer cells to elicit drug resistance have been suggested in the literature.
      Here, we summarize and discuss the current state of the literature on the role of
      obesity and leptin on chemoresistance, particularly as it relates to breast and
      pancreatic cancers. We focus on the role of leptin and its significance in
      possibly driving these proposed chemoresistance mechanisms, and examine its
      effects on cancer cell survival signals and expansion of the cancer stem cell sub
      populations.

PMID- 28439493
TI  - Targeted therapies in breast cancer: New challenges to fight against resistance.
AB  - Breast cancer is the most common type of cancer found in women and today
      represents a significant challenge to public health. With the latest
      breakthroughs in molecular biology and immunotherapy, very specific targeted
      therapies have been tailored to the specific pathophysiology of different types
      of breast cancers. These recent developments have contributed to a more efficient
      and specific treatment protocol in breast cancer patients. However, the main
      challenge to be further investigated still remains the emergence of therapeutic
      resistance mechanisms, which develop soon after the onset of therapy and need
      urgent attention and further elucidation. What are the recent emerging molecular
      resistance mechanisms in breast cancer targeted therapy and what are the best
      strategies to apply in order to circumvent this important obstacle? The main
      scope of this review is to provide a thorough update of recent developments in
      the field and discuss future prospects for preventing resistance mechanisms in
      the quest to increase overall survival of patients suffering from the disease.

PMID- 28439494
TI  - How best to manage gastrointestinal stromal tumor.
AB  - Gastrointestinal stromal tumors (GISTs) are rare but most common nonepithelial
      tumor of gastrointestinal tract. They are often found incidentally on computed
      tomography and endoscopic investigations. Increasing knowledge of the
      pathogenesis of GISTs and the advent of tyrosine kinase inhibitors revolutionized
      the management of GISTs. The newer advanced endoscopic techniques have challenged
      the conventional surgery although the true efficacy and safety of endoscopic
      approach is not clear at this time. This review article focuses on pathogenesis,
      diagnosis and management of GISTs.

PMID- 28439495
TI  - Immunotherapies in sarcoma: Updates and future perspectives.
AB  - Sarcomas are malignant tumors that are characterized by a wide diversity of
      subtypes with various cytogenetic profiles. Despite major treatment
      breakthroughs, standard treatment modalities combining chemotherapy,
      radiotherapy, and surgery failed to improve overall survival. Therefore, high
      expectations are foreseen with immunotherapy upon its maturation and better
      understanding of its mechanism of action. This paper presents a targeted review
      of the published data and ongoing clinical trials in immunotherapies of sarcomas,
      mainly adoptive cell therapies, cancer vaccines and immune checkpoint inhibitors.

PMID- 28439496
TI  - Bethesda System for Reporting Thyroid Cytopathology: A three-year study at a
      tertiary care referral center in Saudi Arabia.
AB  - AIM: To stratify the malignancy risks in thyroid nodules in a tertiary care
      referral center using the Bethesda system. METHODS: From January, 2012 to
      December, 2014, a retrospective analysis was performed among 1188 patients (15-90
      years) who had 1433 thyroid nodules and fine-needle aspiration at Prince Sultan
      Military Medical City, Saudi Arabia. All thyroid cyto-pathological slides and
      ultra sound reports were reviewed and classified according to the Bethesda System
      for Reporting Thyroid Cytopathology. Age, gender, cytological features and
      histological types of the thyroid cancer were collected from patients' medical
      chart and cytopathology reports. RESULTS: There were 124 total cases of
      malignancy on resection, giving an overall surgical yield malignancy of 33.6%.
      Majority of the thyroid cancer nodules (n = 57, 46%) in Bethesda VI category
      followed by Bethesda IV (n = 25, 20.2%). Almost 40% of the cancer nodules in 31
      45 age group in both sex. Papillary thyroid carcinoma (PTC) was the most common
      form of thyroid cancer among the study population (111, 89.6%) followed by 8.9%
      of follicular thyroid carcinoma (FTC), 0.8% of medullary carcinoma and 0.8% of
      anaplastic carcinoma. Among the Bethesda IV category 68% thyroid nodules were PTC
      and 32% FTC. CONCLUSION: The malignancy values reported in our research were
      constant and comparable with the results of other published data with respect to
      the risk of malignancy. Patients with follicular neoplasm/suspicious for
      follicular neoplasm and suspicious of malignancy categories, total thyroidectomy
      is indicted because of the substantial risk of malignancy.

PMID- 28439497
TI  - Study of recombinant human interleukin-12 for treatment of complications after
      radiotherapy for tumor patients.
AB  - AIM: To evaluate the treatment effects of recombinant human interleukin-12 (rhIL
      12) on radiotherapy complications, such as severe myelosuppression or
      pancytopenia, the decline or imbalance of immune function, etc. METHODS: The
      patients received high-dose and short-course precise radiotherapy, such as Cyber
      knife and image-guided radiotherapy (IGRT), which can cause myelosuppression or
      pancytopenia and immune function decline within a short time. One-hundred
      subjects were enrolled in the study, and 50 were randomized to a treatment group
      which used rhIL-12 and 50 were randomized to a control group which used
      symptomatic and supportive therapy after radiotherapy. The 50 subjects in the
      treatment group were further divided into five subgroups and intervened with rhIL
      12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect
      relationship was observed. RESULTS: RhIL-12 significantly attenuated the decrease
      of peripheral blood cells in the treatment group, and immune function was
      improved after treatment. Due to the different radiation doses, there was a
      fluctuation within 12 h after treatment but mostly showing an increasing trend.
      As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed
      low fever after administration, 1 patient in the 200 ng/kg subgroup and 2
      patients in the 250 ng/kg subgroup showed mild impairment of liver function
      during the observation period. CONCLUSION: RhIL-12 has effective therapeutic and
      protective effects on complications following radiotherapy, such as the decline
      of blood cells, myelosuppression and the decline or imbalance of immune function,
      which indicated good prospects for development and application.

PMID- 28439498
TI  - Gastric and duodenal polyps in familial adenomatous polyposis patients:
      Conventional endoscopy vs virtual chromoendoscopy (fujinon intelligent color
      enhancement) in dysplasia evaluation.
AB  - AIM: To test the fujinon intelligent color enhancement (FICE) in identifying
      dysplastic or adenomatous polyps in familial adenomatous polyposis (FAP)
      patients. METHODS: Seventy-six consecutive FAP patients, already treated by
      colectomy and members of sixty-five families, were enrolled. A FICE system for
      the upper gastro-intestinal tract with an electronic endoscope system and a
      standard duodenoscope (for side-viewing examination) were used by two expert
      examiners. Endoscopic resection was performed with diathermic loop for polyps >=
      6 mm and with forceps for polyps < 6 mm. Formalin-fixed biopsy specimens were
      analyzed by two expert gastrointestinal pathologists blinded to size, location
      and number of FAP-associated fundic gland polyps. RESULTS: Sixty-nine (90.8%)
      patients had gastric polyps (34 only in the corpus-fundus, 7 only in the antrum
      and 28 in the whole stomach) and 52 (68.4%) in duodenum (7 in the bulb, 35 in
      second/third duodenal portion, 10 both in the bulb and the second portion of
      duodenum). In the stomach fundus after FICE evaluation, 10 more polyps were
      removed from 10 patients for suspicious features of dysplasia or adenomas, but
      they were classified as cystic fundic gland after histology. In the antrum FICE
      identified more polyps than traditional endoscopy, showing a better tendency to
      identify adenomas and displastic areas. In the duodenum FICE added a significant
      advantage in identifying adenomas in the bulb and identified more polyps in the
      II/III portion. CONCLUSION: FICE significantly increases adenoma detection rate
      in FAP patients but does not change any Spigelman stage and thus does not modify
      patient's prognosis and treatment strategies.

PMID- 28439500
TI  - Chronic Toxoplasma gondii Infection Exacerbates Secondary Polymicrobial Sepsis.
AB  - Sepsis is a severe syndrome that arises when the host response to an insult is
      exacerbated, leading to organ failure and frequently to death. How a chronic
      infection that causes a prolonged Th1 expansion affects the course of sepsis is
      unknown. In this study, we showed that mice chronically infected with Toxoplasma
      gondii were more susceptible to sepsis induced by cecal ligation and puncture
      (CLP). Although T. gondii-infected mice exhibited efficient control of the
      bacterial burden, they showed increased mortality compared to the control groups.
      Mechanistically, chronic T. gondii infection induces the suppression of Th2
      lymphocytes via Gata3-repressive methylation and simultaneously induces long
      lived IFN-gamma-producing CD4+ T lymphocytes, which promotes systemic
      inflammation that is harmful during CLP. Chronic T. gondii infection intensifies
      local and systemic Th1 cytokines as well as nitric oxide production, which
      reduces systolic and diastolic arterial blood pressures after sepsis induction,
      thus predisposing the host to septic shock. Blockade of IFN-gamma prevented
      arterial hypotension and prolonged the host lifespan by reducing the cytokine
      storm. Interestingly, these data mirrored our observation in septic patients, in
      which sepsis severity was positively correlated to increased levels of IFN-gamma
      in patients who were serologically positive for T. gondii. Collectively, these
      data demonstrated that chronic infection with T. gondii is a critical factor for
      sepsis severity that needs to be considered when designing strategies to prevent
      and control the outcome of this devastating disease.

PMID- 28439499
TI  - Tick-Pathogen Interactions and Vector Competence: Identification of Molecular
      Drivers for Tick-Borne Diseases.
AB  - Ticks and the pathogens they transmit constitute a growing burden for human and
      animal health worldwide. Vector competence is a component of vectorial capacity
      and depends on genetic determinants affecting the ability of a vector to transmit
      a pathogen. These determinants affect traits such as tick-host-pathogen and
      susceptibility to pathogen infection. Therefore, the elucidation of the
      mechanisms involved in tick-pathogen interactions that affect vector competence
      is essential for the identification of molecular drivers for tick-borne diseases.
      In this review, we provide a comprehensive overview of tick-pathogen molecular
      interactions for bacteria, viruses, and protozoa affecting human and animal
      health. Additionally, the impact of tick microbiome on these interactions was
      considered. Results show that different pathogens evolved similar strategies such
      as manipulation of the immune response to infect vectors and facilitate
      multiplication and transmission. Furthermore, some of these strategies may be
      used by pathogens to infect both tick and mammalian hosts. Identification of
      interactions that promote tick survival, spread, and pathogen transmission
      provides the opportunity to disrupt these interactions and lead to a reduction in
      tick burden and the prevalence of tick-borne diseases. Targeting some of the
      similar mechanisms used by the pathogens for infection and transmission by ticks
      may assist in development of preventative strategies against multiple tick-borne
      diseases.

PMID- 28439502
TI  - Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of
      Candida albicans to Fluconazole.
AB  - In this study, we found that ambroxol hydrochloride (128 MUg/mL) exhibits
      synergistic antifungal effects in combination with fluconazole (2 MUg/mL) against
      resistant planktonic Candida albicans (C. albicans) cells. This combination also
      exhibited synergistic effects against resistant C. albicans biofilms in different
      stages (4, 8, and 12 h) according to the microdilution method. In vitro data were
      further confirmed by the success of this combination in treating Galleria
      mellonella infected by resistant C. albicans. With respect to the synergistic
      mechanism, our result revealed that ambroxol hydrochloride has an effect on the
      drug transporters of resistant C. albicans, increasing the uptake and decreasing
      the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the
      first study to investigate the in vitro and in vivo antifungal effects, as well
      as the possible synergistic mechanism of ambroxol hydrochloride in combination
      with fluconazole against resistant C. albicans. The results show the potential
      role for this drug combination as a therapeutic alternative to treat resistant C.
      albicans and provide insights into the development of antifungal targets and new
      antifungal agents.

PMID- 28439503
TI  - Circulating cell-free nucleic acids as potential biomarkers for sarcopenia: a
      step toward personalized medicine.
AB  - Sarcopenia is an age-related loss of muscle mass and function, leading to
      disability, morbidity and increased mortality in older people. Given the
      relatively high prevalence and related- outcome of the disease, correct
      diagnosis, screening, monitoring and treatment of sarcopenia are needed in
      clinical practice. Recent researches have focused on cell-free nucleic acids,
      which are released into the circulation following cell death, as a potential
      biomarker of aging and systematic inflammation. It seems that the diagnosis and
      treatment of sarcopenia can be possible by the help of the analysis of cell-free
      nucleic acids as noninvasive method.

PMID- 28439501
TI  - The Cell Biology of the Trichosporon-Host Interaction.
AB  - Fungi of the genus Trichosporon are increasingly recognized as causative agents
      of superficial and invasive fungal disease in humans. Although most species are
      considered commensals of the human skin and gastrointestinal tract, these
      basidiomycetes are an increasing cause of fungal disease among immunocompromised
      hosts, such as hematological patients and solid organ transplant recipients. The
      initiation of commensal or pathogenic programs by Trichosporon spp. involves the
      adaptation to the host microenvironment and its immune system. However, the exact
      virulence factors activated upon the transition to a pathogenic lifestyle,
      including the intricate biology of the cell wall, and how these interact with and
      subvert the host immune responses remain largely unknown. Here, we revisit our
      current understanding of the virulence attributes of Trichosporon spp.,
      particularly T. asahii, and their interaction with the host immune system, and
      accommodate this knowledge within novel perspectives on fungal diagnostics and
      therapeutics.

PMID- 28439504
TI  - From WWII to Kingston, Ontario: The History of Queen's University School of
      Medicine, Division of Plastic and Reconstructive Surgery.
AB  - OBJECTIVE: To describe the origin and development of the Division of Plastic and
      Reconstructive Surgery at the Queen's University School of Medicine (Kingston,
      Ontario). METHODS: Resarch ethics board approval and privacy agreements from the
      Kingston General Hospital (KGH, Kingston, Ontario) medical archives were
      obtained. Primary and secondary data sources were identified. A systematic
      examination of newspaper archives, research literature, KGH medical advisory
      committee meeting minutes, and testimonies from Dr Kenneth Wyllie and Dr John
      Davidson were obtained. RESULTS: In 1949, Dr Albert Ross Tilley arrived at
      Queen's University in Kingston, Ontario. There, Tilley initiated the Burn Unit at
      the KGH and began monthly teaching during the academic semester. Ken Wyllie (Meds
      '55), Lloyd Carlson (Meds '57) and John Emery (Meds '57) were the notable progeny
      of his early initiatives. In 1963, Kenneth Wyllie founded the Division of Plastic
      and Reconstructive Surgery in Kingston, Ontario, having completed plastic surgery
      training in Toronto and Edinburgh with experiences in Stockholm (Sweden), Paris
      (France) and Baltimore (Maryland, USA). He was shortly joined by Pat Shoemaker
      (Meds '66). John Davidson (Meds '82) arrived in 1989, bringing an interest in
      microsurgery and critical inquiry to the division. Five notable surgeons,
      Cartotto (Meds '88), Watkins, Watters, Meathrel (Meds '03) and McKay, further
      enhanced the Division's clinical and academic mission. CONCLUSIONS: The
      collective activity of the Division of Plastic and Reconstructive Surgery at
      Queen's School of Medicine in its 66-year history has encouraged more than 40
      others to pursue distinguished careers in the specialty throughout North America,
      including three past presidents of the Canadian Society of Plastic Surgeons.

PMID- 28439505
TI  - Distant blunt forceps dissection in tissue expander insertion: A novel technique.
AB  - Tissue expansion using implantable expanders is a useful means of generating
      surplus tissue for reconstruction of defects such as scarring following burns.
      The authors describe their technique of incisions distant to the desired location
      of expander placement, and remote dissection of the expander pocket with
      hydrodissection and blunt forceps. A total of 81 expanders were placed in 30
      consecutive patients, 81% of whom had burn scars due for reconstruction. During
      preparation, no complications, such as bleeding, were encountered, except one
      case with severe subdermal fibrosis, in which bleeding was stopped through brief
      application of pressure. Postoperatively, no complications were encountered in
      76% of patients; however, 16.6% exhibited surgical site infection, which was
      managed conservatively and was correlated with a high number of expanders
      implanted at once. One patient experienced hematoma formation that resolved
      spontaneously, and one instance of expander extrusion and subsequent removal
      occurred. Receiving >=2 expanders at the same time was statistically associated
      with higher risk for complication(s). The authors' complication rates were
      moderate and comparable with open or endoscopic approaches. Time of expansion is
      reduced compared with the open approach due to distant incision placement and
      immediate usability. Cost effectiveness appeared to be better using only
      inexpensive forceps, rather than elaborate and costly endoscopic equipment.

PMID- 28439506
TI  - Evaluation of a new tension relief system for securing wound closure: A single
      centre, Chinese cohort study.
AB  - BACKGROUND: Wounds that have been closed under excessive tension, and skin
      defects that cannot be closed primarily, pose a daily challenge for the
      reconstructive surgeon. OBJECTIVE: To evaluate a new tension relief system (TRS)
      device for skin stretching and secure wound closure. METHODS: From September 2013
      to March 2014, a consecutive series of 41 Chinese patients with 43 wounds were
      enrolled for application of 50 cycles of TRS therapy. TRS was used for two main
      clinical applications: closure of a variety of surgical/traumatic wounds; and
      securing wound closure after high-tension suture closure. Basic information and
      details regarding this therapy and its complications were recorded. Follow-up
      visits were conducted three to six months after wound closure. RESULTS: Mean
      residual wound width decreased approximately 20% every two days during cycles of
      TRS therapy. Infection was the most common complication (five cases). Other
      complications included dehiscence (two cases) and pressure ulcer (one case). At
      the six-month follow-up visit, (21 wounds in 20 patients), both the extent of
      healing and the scar were acceptable. DISCUSSION: There are no absolute
      contraindications to TRS therapy. The authors have formulated instructions for
      the prevention and treatment of the most common complications. CONCLUSIONS: The
      results demonstrate that TRS therapy is a simple, effective method for primary
      closure of difficult wounds, and large skin and soft-tissue defects. Larger
      randomized studies are required to further evaluate of the effectiveness,
      indications, complications and cost effectiveness of this innovative TRS therapy.

PMID- 28439507
TI  - Evaluation of the complex treatment for congenital blepharoptosis.
AB  - OBJECTIVE: To evaluate the results of treatment of congenital blepharoptosis
      (CBP) using selected surgical methods; and to evaluate concomitant visual system
      disorders. METHODS: Between 2001 and 2010, 52 children with CBP underwent
      surgical correction of CBP using the modified method of Mustarde, the original
      Mustarde method or frontal suspension at the Department of Plastic Surgery,
      Medical University of Lodz (Poland). Based on the results of ophthalmic and
      orthoptic examination, and standard measurements, postoperative differences in
      the position and symmetry of the upper eyelids, complications, and visual system
      abnormalities were analyzed. RESULTS: Very good results were obtained in all
      patients with mild unilateral CBP. The results in patients with moderate and
      severe unilateral CBP, and in bilateral anomaly after correction using Mustarde's
      method or the modified Mustarde's method, were also very good. Complications
      included lagophthalmos (15.4%) and undercorrection (3.8%). Visual system
      disorders, mainly amblyopia, resulting from strabismus, astigmatism,
      anisometropia and CBP, were observed in 88.5% of patients. CONCLUSIONS: Complex
      ophthalmic examination and measurements in individuals with CBP enable correct
      diagnosis, selection of appropriate treatment method and timing of surgical
      intervention. Postoperative results in patients with CBP supported the efficacy
      of the methods that shortened the levator palpebrae superioris. Supplementing
      with Mustarde's modified method contributed to an increase in the number of
      favourable postoperative results.

PMID- 28439508
TI  - An evaluation of accessibility and content of microsurgery fellowship websites.
AB  - BACKGROUND: Websites for residency and fellowship programs serve as effective
      educational and recruitment tools. OBJECTIVE: To evaluate the accessibility and
      content of fellowship websites that are commonly used by microsurgery applicants
      for career development. METHODS: A list of one-year microsurgery fellowship
      websites (MFWs) was compiled by visiting the centralized American Society for
      Reconstructive Microsurgery (ASRM) website, followed by performing an extensive
      'Google' search in October 2015. Accessibility of MFWs was assessed. Website
      content regarding key recruitment and education variables was also
      comprehensively reviewed. Website content was correlated with program
      characteristics using t tests and ANOVA (two-tailed; P<0.05 was considered to be
      statistically significant). RESULTS: A list of 53 eligible programs was compiled.
      Only 15 of 51 (29%) ASRM program links were functional. On average, the combined
      content from ASRM website and individual MFWs had 2.91 of 6 recruitment variables
      and 1.32 of 6 education variables, respectively. The majority of programs listed
      'eligibility criteria' (87%) and 'general information' (87%). 'Evaluation
      criteria' were most poorly reported (4%). Recruitment score was higher for United
      States programs compared with international counterparts (51% versus 33%,
      respectively; P=0.02). It was also higher in programs that focus on 'extremity'
      versus 'breast' (58% versus 37%; P=0.0028). Education scores did not differ
      according to location, program size, subspecialty of focus or participation in
      the Microsurgery Match process. CONCLUSION: Information regarding recruitment and
      education on most MFWs is scarce. Academic institutions should keep website
      content up to date and comprehensive to better assist candidates in the
      application process.

PMID- 28439509
TI  - Triangular lipodermal flaps in Wise pattern reduction mammoplasty (superomedial
      pedicle): A novel technique to reduce T-junction necrosis.
AB  - BACKGROUND: Although Wise pattern reduction mammoplasty is one of the most
      prevalent procedures providing satisfactory cutaneous reduction, it is at the
      expense of inevitable lengthier scars and wound complications, especially at the
      inverted T junction. OBJECTIVE: To describe a novel technique providing tension
      free closure at the T junction through performing triangular lipodermal flaps.
      The aim is to alleviate skin tension, thus reducing skin necrosis, dehiscence and
      excessive scarring at the T junction. METHODS: One hundred seventy-three
      consecutive procedures were performed on 137 patients between 2009 and 2013. Data
      collected included demographics, perioperative morbidity and resected breast
      tissue weight. The follow-up period ranged from three to 30 months; early and
      late postoperative complications and patient satisfaction were recorded. RESULTS:
      Superficial epidermolysis without T-junction dehiscence was experienced in eight
      (4.6%) procedures while five (2.9%) procedures developed full-thickness wound
      dehiscence. Ninety-four percent of patients were highly satisfied with the
      outcome. CONCLUSIONS: The technique is safe, versatile and easy to execute,
      providing a tension-free zone and acting as internal dermal sling, thus providing
      better wound healing with more favourable aesthetic outcome and maintaining
      breast projection.

PMID- 28439510
TI  - Is antibiotic prophylaxis in breast augmentation necessary? A prospective study.
AB  - BACKGROUND: The role of prophylactic antibiotics in breast augmentation remains
      controversial. However, the majority of surgeons are administering antibiotics.
      OBJECTIVE: To investigate the effect of antibiotic(s) use in the incidence of
      infection and capsular contracture following breast augmentation. METHODS: From
      September 2004 to November 2010, 180 patients underwent primary bilateral breast
      augmentation. They were prospectively divided into two equal groups: in group A
      (n=90), no antibiotics were given and, in group B (n=90), only one intravenous
      dose of cephalosporin was administered during the induction of general
      anesthesia. Preoperative data included age, body mass index, smoking status,
      medical history and implant volume. All operations were performed by the same
      surgeon using the same surgical technique and implant type. No drains were used.
      Operative data included operative time and estimated blood loss. Patients were
      evaluated for complications such as infection, hematoma and capsular contracture.
      The study concluded when all of the patients underwent the one-year follow-up.
      The Student's t test was used to analyze the results. RESULTS: All patients
      completed the study and both groups had similar demographic data. No differences
      in operative data were observed. The mean operative time was 35 min and the mean
      blood loss was found to be minimal. In group A, no implant infections were
      reported, while a wound infection that occurred was treated successfully with
      oral antibiotics. In group B, no implant or wound infection was noticed. No
      capsular contractures or hematomas were observed. CONCLUSIONS: The number of
      patients who underwent primary breast augmentation without antibiotics (n=90) was
      insufficient to draw any definitive conclusions. However, the present prospective
      study demonstrated that prophylactic use of antibiotics in breast augmentation
      had no significant effect on infection and capsular contracture rates. Further
      randomized clinical trials, in combination with guidelines from aesthetic plastic
      surgery societies, appear to be warranted.

PMID- 28439511
TI  - Forty-five degree cutting septoplasty.
AB  - BACKGROUND: The crooked nose represents a challenge for rhinoplasty surgeons, and
      many methods have been proposed for management; however, there is no ideal method
      for treatment. Accordingly, the 45 degrees  cutting septoplasty technique, which
      involves a 45 degrees  cut at the junction of the L-shaped strut and
      repositioning it to achieve a straight septum is proposed. METHODS: From October
      2010 to September 2014, 43 patients underwent the 45 degrees  cutting septoplasty
      technique. There were 28 men and 15 women, with ages ranging from 20 to 58 years
      (mean, 33 years). Standardized photographs were obtained at every visit.
      Established photogrammetric parameters were used to describe the degree of
      correction: Correction rate = (preoperative total deviation - postoperative
      residual deviation)/preoperative total deviation * 100% was proposed. RESULTS:
      The mean follow-up period for all patients was 12.3 months. The mean preoperative
      deviation was 64.3 degrees  and the mean postoperative deviation was 2.7 degrees
      ; the overall correction rate was 95.8%. One patient experienced composite
      implant deviation two weeks postoperatively and underwent revision rhinoplasty.
      There were no infections, hematomas or postoperative bleeding. CONCLUSION: Based
      on the clinical observation of all patients during the follow-up period, the 45
      degrees  cutting septoplasty technique was shown to be effective for the
      treatment of crooked nose.

PMID- 28439513
TI  - Oral Exam.

PMID- 28439512
TI  - Assessing the effects of melatonin and N-acetylcysteine on the McFarlane flap
      using a rat model.
AB  - OBJECTIVE: To determine the effects of N-acetylcysteine (NAC) and melatonin,
      alone and in combination, on McFarlane flap viability in a rat model. METHODS:
      Forty Wistar rats were divided into four groups and received daily
      intraperitoneal injections for one week before surgery: control (sham [n=10]);
      melatonin (n=10); NAC (n=10); and NAC+melatonin (n=10). One week after surgery,
      the experiment was terminated and photographs were taken for topographic studies.
      A transillumination study was performed to observe vascularization in the flaps
      and biopsies were obtained for histopathological studies. RESULTS: Flap viability
      was significantly greater in the antioxidant- (ie, NAC and melatonin) treated
      groups compared with the control group; however, there were no significant
      differences among the groups that received antioxidants. CONCLUSIONS: Melatonin
      and NAC are important antioxidants that can be used alone or in combination to
      increase flap viability and prevent distal necrosis in rats.

PMID- 28439514
TI  - Mergers and acquisitions: Corporate inversions.

PMID- 28439516
TI  - Engineering Muscle Networks in 3D Gelatin Methacryloyl Hydrogels: Influence of
      Mechanical Stiffness and Geometrical Confinement.
AB  - In this work, the influence of mechanical stiffness and geometrical confinement
      on the 3D culture of myoblast-laden gelatin methacryloyl (GelMA) photo
      crosslinkable hydrogels was evaluated in terms of in vitro myogenesis. We
      formulated a set of cell-laden GelMA hydrogels with a compressive modulus in the
      range 1 / 17 kPa, obtained by varying GelMA concentration and degree of cross
      linking. C2C12 myoblasts were chosen as the cell model to investigate the
      supportiveness of different GelMA hydrogels toward myotube formation up to 2
      weeks. Results showed that the hydrogels with a stiffness in the range 1 / 3 kPa
      provided enhanced support to C2C12 differentiation in terms of myotube number,
      rate of formation, and space distribution. Finally, we studied the influence of
      geometrical confinement on myotube orientation by confining cells within thin
      hydrogel slabs having different cross sections: (i) 2,000 MUm * 2,000 MUm, (ii)
      1,000 MUm * 1,000 MUm, and (iii) 500 MUm * 500 MUm. The obtained results showed
      that by reducing the cross section, i.e., by increasing the level of confinement
      myotubes were more closely packed and formed aligned myostructures that better
      mimicked the native morphology of skeletal muscle.

PMID- 28439515
TI  - Endogenous Retroviruses: With Us and against Us.
AB  - Mammalian genomes are scattered with thousands of copies of endogenous
      retroviruses (ERVs), mobile genetic elements that are relics of ancient
      retroviral infections. After inserting copies into the germ line of a host, most
      ERVs accumulate mutations that prevent the normal assembly of infectious viral
      particles, becoming trapped in host genomes and unable to leave to infect other
      cells. While most copies of ERVs are inactive, some are transcribed and encode
      the proteins needed to generate new insertions at novel loci. In some cases, old
      copies are removed via recombination and other mechanisms. This creates a
      shifting landscape of ERV copies within host genomes. New insertions can disrupt
      normal expression of nearby genes via directly inserting into key regulatory
      elements or by containing regulatory motifs within their sequences. Further, the
      transcriptional silencing of ERVs via epigenetic modification may result in
      changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can
      be potent sources of regulatory disruption as well as genetic innovation. Here,
      we provide a brief review of the association between ERVs and gene expression,
      especially as observed in pre-implantation development and placentation.
      Moreover, we will describe how disruption of the regulated mechanisms of ERVs may
      impact somatic tissues, mostly in the context of human disease, including cancer,
      neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent
      discovery that some ERVs may have been pressed into the service of their host
      genomes to aid in the innate immune response to exogenous viral infections.

PMID- 28439517
TI  - Incidence and Risk Factors for Organ/Space Infection after Radiofrequency
      Assisted Hepatectomy or Ablation of Liver Tumors in a Single Center: More than
      Meets the Eye.
AB  - INTRODUCTION: Surgical site infections (SSIs) and especially organ/space
      infection (O/SI) after resection or ablation of liver tumors are associated with
      increased morbidity and mortality. A secondary blood stream infection (BSI) is
      considered an O/SI but the exact prevalence is unknown. We aimed to investigate
      the incidence of O/SI and BSIs in a cohort of consecutive patients after liver
      resection or ablation, to seek for a possible connection between them and to
      search for potential risk factors. MATERIALS AND METHODS: We reviewed all
      patients who underwent hepatic resection or intraoperative liver ablation between
      January 2012 and December 2016 in our department. We focused on age, gender,
      Child-Pugh score, preoperative biliary drainage, indication for surgery, type of
      resection, resection or ablation of tumor, need for bilioenteric reconstruction,
      additional procedure to hepatectomy, blood transfusion, operative time,
      postoperative admission to ICU, and antibiotic chemoprophylaxis. All positive
      cultures from intra-abdominal fluids and blood were recorded. O/SI and BSIs were
      diagnosed by the criteria set by Centers for Disease Control. All variables were
      compared between the group with O/SI and the group without infection. BSIs were
      associated with these infections also. RESULTS: Eighty-one consecutive patients
      with a mean age of 64 years were enrolled. Fifteen patients presented a positive
      culture postoperatively: intra-abdominal fluid in eight, blood cultures in six,
      and both blood and intra-abdominal fluid in one patient. The directly estimated
      incidence of O/SI amounted to 11.1%. Four blood cultures were secondary to O/SI,
      and the remaining two secondary to central line catheter. O/SI was diagnosed
      indirectly, through the BSI in an additional 4.9% of the patients, raising the
      incidence of SSI to 16%. Among the factors studied, only admission to the ICU was
      found to be statistically significant as a risk factor for the development of
      O/SI (p = 0.026). CONCLUSION: O/SI should be actively seeked for after liver
      surgery including blood cultures. Patients with affected physical status,
      comorbidities are in greater risk of developing O/SI.

PMID- 28439519
TI  - Structured illumination diffuse optical tomography for noninvasive functional
      neuroimaging in mice.
AB  - Optical intrinsic signal (OIS) imaging has been a powerful tool for capturing
      functional brain hemodynamics in rodents. Recent wide field-of-view
      implementations of OIS have provided efficient maps of functional connectivity
      from spontaneous brain activity in mice. However, OIS requires scalp retraction
      and is limited to superficial cortical tissues. Diffuse optical tomography (DOT)
      techniques provide noninvasive imaging, but previous DOT systems for rodent
      neuroimaging have been limited either by sparse spatial sampling or by slow
      speed. Here, we develop a DOT system with asymmetric source-detector sampling
      that combines the high-density spatial sampling (0.4 mm) detection of a
      scientific complementary metal-oxide-semiconductor camera with the rapid (2 Hz)
      imaging of a few ([Formula: see text]) structured illumination (SI) patterns.
      Analysis techniques are developed to take advantage of the system's flexibility
      and optimize trade-offs among spatial sampling, imaging speed, and signal-to
      noise ratio. An effective source-detector separation for the SI patterns was
      developed and compared with light intensity for a quantitative assessment of data
      quality. The light fall-off versus effective distance was also used for in situ
      empirical optimization of our light model. We demonstrated the feasibility of
      this technique by noninvasively mapping the functional response in the
      somatosensory cortex of the mouse following electrical stimulation of the
      forepaw.

PMID- 28439518
TI  - Diabetes, adult neurogenesis and brain remodeling: New insights from rodent and
      zebrafish models.
AB  - The prevalence of diabetes rapidly increased during the last decades in
      association with important changes in lifestyle. Diabetes and hyperglycemia are
      well-known for inducing deleterious effects on physiologic processes, increasing
      for instance cardiovascular diseases, nephropathy, retinopathy and foot
      ulceration. Interestingly, diabetes also impairs brain morphology and functions
      such as (1) decreased neurogenesis (proliferation, differentiation and cell
      survival), (2) decreased brain volumes, (3) increased blood-brain barrier
      leakage, (4) increased cognitive impairments, as well as (5) increased stroke
      incidence and worse neurologic outcomes following stroke. Importantly, diabetes
      is positively associated with a higher risk to develop Alzheimer disease. In this
      context, we aim at reviewing the impact of diabetes on neural stem cell
      proliferation, newborn cell differentiation and survival in a homeostatic context
      or following stroke. We also report the effects of hyper- and hypoglycemia on the
      blood-brain barrier physiology through modifications of tight junctions and
      transporters. Finally, we discuss the implication of diabetes on cognition and
      behavior.

PMID- 28439520
TI  - Relationship between relative cerebral blood flow, relative cerebral blood
      volume, and relative cerebral metabolic rate of oxygen in the preterm neonatal
      brain.
AB  - The mechanisms responsible for coupling between relative cerebral blood flow
      (rCBF), relative cerebral blood volume (rCBV), and relative cerebral metabolic
      rate of oxygen ([Formula: see text]), an important function of the
      microcirculation in preterm infants, remain unclear. Identification of a causal
      relationship between rCBF-rCBV and [Formula: see text] in preterms may,
      therefore, help to elucidate the principles of cortical hemodynamics during
      development. We simultaneously recorded rCBF and rCBV and estimated [Formula: see
      text] by two independent acquisition systems: diffuse correlation spectroscopy
      and near-infrared spectroscopy, respectively, in 10 preterms aged between 28 and
      35 weeks of gestational age. Transfer entropy was calculated in order to
      determine the directionality between rCBF-rCBV and [Formula: see text]. The
      surrogate method was applied to determine statistical significance. The results
      show that rCBV and [Formula: see text] have a predominant driving influence on
      rCBF at the resting state in the preterm neonatal brain. Statistical analysis
      robustly detected the correct directionality of rCBV on rCBF and [Formula: see
      text] on rCBF. This study helps to clarify the early organization of the rCBV
      rCBF and [Formula: see text] inter-relationship in the immature cortex.

PMID- 28439521
TI  - Dynamic electronic collimation method for 3-D catheter tracking on a scanning
      beam digital x-ray system.
AB  - Scanning-beam digital x-ray (SBDX) is an inverse geometry x-ray fluoroscopy
      system capable of tomosynthesis-based 3-D catheter tracking. This work proposes a
      method of dose-reduced 3-D catheter tracking using dynamic electronic collimation
      (DEC) of the SBDX scanning x-ray tube. This is achieved through the selective
      deactivation of focal spot positions not needed for the catheter tracking task.
      The technique was retrospectively evaluated with SBDX detector data recorded
      during a phantom study. DEC imaging of a catheter tip at isocenter required 340
      active focal spots per frame versus 4473 spots in full field-of-view (FOV) mode.
      The dose-area product (DAP) and peak skin dose (PSD) for DEC versus full FOV
      scanning were calculated using an SBDX Monte Carlo simulation code. The average
      DAP was reduced to 7.8% of the full FOV value, consistent with the relative
      number of active focal spots (7.6%). For image sequences with a moving catheter,
      PSD was 33.6% to 34.8% of the full FOV value. The root-mean-squared-deviation
      between DEC-based 3-D tracking coordinates and full FOV 3-D tracking coordinates
      was less than 0.1 mm. The 3-D distance between the tracked tip and the sheath
      centerline averaged 0.75 mm. DEC is a feasible method for dose reduction during
      SBDX 3-D catheter tracking.

PMID- 28439522
TI  - Automatic image quality assessment and measurement of fetal head in two
      dimensional ultrasound image.
AB  - Owing to the inconsistent image quality existing in routine obstetric ultrasound
      (US) scans that leads to a large intraobserver and interobserver variability, the
      aim of this study is to develop a quality-assured, fully automated US fetal head
      measurement system. A texton-based fetal head segmentation is used as a
      prerequisite step to obtain the head region. Textons are calculated using a
      filter bank designed specific for US fetal head structure. Both shape- and
      anatomic-based features calculated from the segmented head region are then fed
      into a random forest classifier to determine the quality of the image (e.g.,
      whether the image is acquired from a correct imaging plane), from which fetal
      head measurements [biparietal diameter (BPD), occipital-frontal diameter (OFD),
      and head circumference (HC)] are derived. The experimental results show a good
      performance of our method for US quality assessment and fetal head measurements.
      The overall precision for automatic image quality assessment is 95.24% with 87.5%
      sensitivity and 100% specificity, while segmentation performance shows 99.27%
      ([Formula: see text]) of accuracy, 97.07% ([Formula: see text]) of sensitivity,
      2.23 mm ([Formula: see text]) of the maximum symmetric contour distance, and 0.84
      mm ([Formula: see text]) of the average symmetric contour distance. The
      statistical analysis results using paired [Formula: see text]-test and Bland
      Altman plots analysis indicate that the 95% limits of agreement for inter
      observer variability between the automated measurements and the senior expert
      measurements are 2.7 mm of BPD, 5.8 mm of OFD, and 10.4 mm of HC, whereas the
      mean differences are [Formula: see text], [Formula: see text], and [Formula: see
      text], respectively. These narrow 95% limits of agreements indicate a good level
      of consistency between the automated and the senior expert's measurements.

PMID- 28439523
TI  - Tsallis entropy and sparse reconstructive dictionary learning for exudate
      detection in diabetic retinopathy.
AB  - Computer-assisted automated exudate detection is crucial for large-scale
      screening of diabetic retinopathy (DR). The motivation of this work is robust and
      accurate detection of low contrast and isolated hard exudates using fundus
      imaging. Gabor filtering is first performed to enhance exudate visibility
      followed by Tsallis entropy thresholding. The obtained candidate exudate pixel
      map is useful for further removal of falsely detected candidates using sparse
      based dictionary learning and classification. Two reconstructive dictionaries are
      learnt using the intensity, gradient, local energy, and transform domain features
      extracted from exudate and background patches of the training fundus images.
      Then, a sparse representation-based classifier separates the true exudate pixels
      from false positives using least reconstruction error. The proposed method is
      evaluated on the publicly available e-ophtha EX and standard DR database
      calibration level 1 (DIARETDB1) databases and high exudate detection performance
      is achieved. In the e-ophtha EX database, mean sensitivity of 85.80% and positive
      predictive value of 57.93% are found. For the DIARETDB1 database, an area under
      the curve of 0.954 is obtained.

PMID- 28439524
TI  - BrainSegNet: a convolutional neural network architecture for automated
      segmentation of human brain structures.
AB  - Automated segmentation of cortical and noncortical human brain structures has
      been hitherto approached using nonrigid registration followed by label fusion. We
      propose an alternative approach for this using a convolutional neural network
      (CNN) which classifies a voxel into one of many structures. Four different kinds
      of two-dimensional and three-dimensional intensity patches are extracted for each
      voxel, providing local and global (context) information to the CNN. The proposed
      approach is evaluated on five different publicly available datasets which differ
      in the number of labels per volume. The obtained mean Dice coefficient varied
      according to the number of labels, for example, it is [Formula: see text] and
      [Formula: see text] for datasets with the least (32) and the most (134) number of
      labels, respectively. These figures are marginally better or on par with those
      obtained with the current state-of-the-art methods on nearly all datasets, at a
      reduced computational time. The consistently good performance of the proposed
      method across datasets and no requirement for registration make it attractive for
      many applications where reduced computational time is necessary.

PMID- 28439525
TI  - Most Likely to Succeed: Long-Run Returns to Adolescent Popularity.
AB  - Sociological explanations for economic success tend toward measures of
      embeddedness in longstanding social institutions, such as race and gender, or
      personal skills represented mainly by educational attainment. In this paper we
      seek a distinctively social foundation for success by investigating the long-term
      association between high school popularity and income. Using rich longitudinal
      data, we find a clear and persistent association between the number of friendship
      nominations received and adult income, even after accounting for the mediating
      influences of diverse personal, family, and work characteristics. This skill is
      distinct from conventional personality measures such as the Big Five, and
      persists long into adulthood. We hypothesize that popularity encapsulates a
      socioemotional skill recognized by peers as the practice of being a good friend
      rather than an indicator of social status.

PMID- 28439526
TI  - Absence of NMDA receptor antibodies in patients with ovarian teratoma without
      encephalitis.

PMID- 28439527
TI  - Precision in neuroimmunology.

PMID- 28439528
TI  - Foveal thinning in neuromyelitis optica: A sign of retinal astrocytopathy?

PMID- 28439529
TI  - Catestatin and orexin-A influence hamster thermic states during hibernation.
AB  - Decreased body temperature during hibernation evokes a neuroprotective effect
      against the frequent neurodegenerative events of ischemic/reperfusion injuries.
      This neuroprotection appears to stem from a direct involvement of orexin-A plus
      the sympathoinhibitory neuroactive peptide catestatin on orexin 2 receptor
      dependent feeding and motor behaviors of the facultative hibernating hamster.

PMID- 28439530
TI  - Using cognitive training studies to unravel the mechanisms by which the
      approximate number system supports symbolic math ability.
AB  - A picture is emerging that preverbal nonsymbolic numerical representations
      derived from the approximate number system (ANS) play an important role in
      mathematical development and sustained mathematical thinking. Functional imaging
      studies are revealing developmental trends in how the brain represents number. We
      propose that combining behavioral and neuroimaging techniques with cognitive
      training approaches will help identify the fundamental relationship between the
      ANS and symbolic mathematics. Understanding this relationship should ultimately
      benefit educators by providing ways to harness the ANS and hopefully improve math
      readiness in young children.

PMID- 28439531
TI  - Genome- and CD4+ T-cell methylome-wide association study of circulating
      trimethylamine-N-oxide in the Genetics of Lipid Lowering Drugs and Diet Network
      (GOLDN).
AB  - BACKGROUND: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has
      emerged as a possible new risk factor for cardiovascular disease. Animal studies
      have shown that circulating TMAO levels are regulated by genetic and
      environmental factors. However, large-scale human studies have failed to
      replicate the observed genetic associations, and epigenetic factors such as DNA
      methylation have never been examined in relation to TMAO levels. METHODS AND
      RESULTS: We used data from the family-based Genetics of Lipid Lowering Drugs and
      Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in
      humans. TMAO was not associated with other plasma markers of cardiovascular
      disease, e.g. lipids or inflammatory cytokines. We first estimated TMAO
      heritability at 27%, indicating a moderate genetic influence. We used 1000
      Genomes imputed data (n=626) to estimate genome-wide associations with TMAO
      levels, adjusting for age, sex, family relationships, and study site. The genome
      wide study yielded one significant hit at the genome-wide level, located in an
      intergenic region on chromosome 4. We subsequently quantified epigenome-wide DNA
      methylation using the Illumina Infinium array on CD4+ T-cells. We tested for
      association of methylation loci with circulating TMAO (n=847), adjusting for age,
      sex, family relationships, and study site as the genome-wide study plus principal
      components capturing CD4+ T-cell purity. Upon adjusting for multiple testing,
      none of the epigenetic findings were statistically significant. CONCLUSIONS: Our
      findings contribute to the growing body of evidence suggesting that neither
      genetic nor epigenetic factors play a critical role in establishing circulating
      TMAO levels in humans.

PMID- 28439532
TI  - Recruiting to preclinical Alzheimer's disease clinical trials through registries.
AB  - Participant registries are repositories of individuals who have expressed
      willingness to learn about studies for which they may be eligible. Registries are
      increasingly being utilized to improve recruitment to preclinical Alzheimer's
      disease (AD) clinical trials, which require large screening efforts to identify
      adequate numbers of participants who meet enrollment criteria. Recruiting to
      preclinical AD trials from registries is made more efficient through registry
      collection of data that permits exclusion of those who will not be eligible and
      identifies individuals most likely to qualify for trials. Such data could include
      self-reported disease family history or other risk factors, but could also
      include cognitive, genetic, or biomarker testing outcomes. Few data are available
      to guide investigators overseeing registries and important ethical questions are
      likely to arise related to their conduct, especially in registries collecting AD
      risk information. This article outlines three areas of consideration for registry
      investigators: informed consent, disclosure, and sponsorship.

PMID- 28439533
TI  - The anatomical placode in reptile scale morphogenesis indicates shared ancestry
      among skin appendages in amniotes.
AB  - Most mammals, birds, and reptiles are readily recognized by their hairs,
      feathers, and scales, respectively. However, the lack of fossil intermediate
      forms between scales and hairs and substantial differences in their morphogenesis
      and protein composition have fueled the controversy pertaining to their potential
      common ancestry for decades. Central to this debate is the apparent lack of an
      "anatomical placode" (that is, a local epidermal thickening characteristic of
      feathers' and hairs' early morphogenesis) in reptile scale development. Hence,
      scenarios have been proposed for the independent development of the anatomical
      placode in birds and mammals and parallel co-option of similar signaling pathways
      for their morphogenesis. Using histological and molecular techniques on
      developmental series of crocodiles and snakes, as well as of unique wild-type and
      EDA (ectodysplasin A)-deficient scaleless mutant lizards, we show for the first
      time that reptiles, including crocodiles and squamates, develop all the
      characteristics of an anatomical placode: columnar cells with reduced
      proliferation rate, as well as canonical spatial expression of placode and
      underlying dermal molecular markers. These results reveal a new evolutionary
      scenario where hairs, feathers, and scales of extant species are homologous
      structures inherited, with modification, from their shared reptilian ancestor's
      skin appendages already characterized by an anatomical placode and associated
      signaling molecules.

PMID- 28439534
TI  - The Arctic Ocean as a dead end for floating plastics in the North Atlantic branch
      of the Thermohaline Circulation.
AB  - The subtropical ocean gyres are recognized as great marine accummulation zones of
      floating plastic debris; however, the possibility of plastic accumulation at
      polar latitudes has been overlooked because of the lack of nearby pollution
      sources. In the present study, the Arctic Ocean was extensively sampled for
      floating plastic debris from the Tara Oceans circumpolar expedition. Although
      plastic debris was scarce or absent in most of the Arctic waters, it reached high
      concentrations (hundreds of thousands of pieces per square kilometer) in the
      northernmost and easternmost areas of the Greenland and Barents seas. The
      fragmentation and typology of the plastic suggested an abundant presence of aged
      debris that originated from distant sources. This hypothesis was corroborated by
      the relatively high ratios of marine surface plastic to local pollution sources.
      Surface circulation models and field data showed that the poleward branch of the
      Thermohaline Circulation transfers floating debris from the North Atlantic to the
      Greenland and Barents seas, which would be a dead end for this plastic conveyor
      belt. Given the limited surface transport of the plastic that accumulated here
      and the mechanisms acting for the downward transport, the seafloor beneath this
      Arctic sector is hypothesized as an important sink of plastic debris.

PMID- 28439536
TI  - Types and rates of forest disturbance in Brazilian Legal Amazon, 2000-2013.
AB  - Deforestation rates in primary humid tropical forests of the Brazilian Legal
      Amazon (BLA) have declined significantly since the early 2000s. Brazil's national
      forest monitoring system provides extensive information for the BLA but lacks
      independent validation and systematic coverage outside of primary forests. We use
      a sample-based approach to consistently quantify 2000-2013 tree cover loss in all
      forest types of the region and characterize the types of forest disturbance. Our
      results provide unbiased forest loss area estimates, which confirm the reduction
      of primary forest clearing (deforestation) documented by official maps. By the
      end of the study period, nonprimary forest clearing, together with primary forest
      degradation within the BLA, became comparable in area to deforestation,
      accounting for an estimated 53% of gross tree cover loss area and 26 to 35% of
      gross aboveground carbon loss. The main type of tree cover loss in all forest
      types was agroindustrial clearing for pasture (63% of total loss area), followed
      by small-scale forest clearing (12%) and agroindustrial clearing for cropland
      (9%), with natural woodlands being directly converted into croplands more often
      than primary forests. Fire accounted for 9% of the 2000-2013 primary forest
      disturbance area, with peak disturbances corresponding to droughts in 2005, 2007,
      and 2010. The rate of selective logging exploitation remained constant throughout
      the study period, contributing to forest fire vulnerability and degradation
      pressures. As the forest land use transition advances within the BLA,
      comprehensive tracking of forest transitions beyond primary forest loss is
      required to achieve accurate carbon accounting and other monitoring objectives.

PMID- 28439537
TI  - The nearly universal link between the age of past knowledge and tomorrow's
      breakthroughs in science and technology: The hotspot.
AB  - Scientists and inventors can draw on an ever-expanding literature for the
      building blocks of tomorrow's ideas, yet little is known about how combinations
      of past work are related to future discoveries. Our analysis parameterizes the
      age distribution of a work's references and revealed three links between the age
      of prior knowledge and hit papers and patents. First, works that cite literature
      with a low mean age and high age variance are in a citation "hotspot"; these
      works double their likelihood of being in the top 5% or better of citations.
      Second, the hotspot is nearly universal in all branches of science and technology
      and is increasingly predictive of a work's future citation impact. Third, a
      scientist or inventor is significantly more likely to write a paper in the
      hotspot when they are coauthoring than whey they are working alone. Our findings
      are based on all 28,426,345 scientific papers in the Web of Science, 1945-2013,
      and all 5,382,833 U.S. patents, 1950-2010, and reveal new antecedents of high
      impact science and the link between prior literature and tomorrow's breakthrough
      ideas.

PMID- 28439535
TI  - A murine preclinical syngeneic transplantation model for breast cancer precision
      medicine.
AB  - We previously demonstrated that altered activity of lysophosphatidic acid in
      murine mammary glands promotes tumorigenesis. We have now established and
      characterized a heterogeneous collection of mouse-derived syngeneic transplants
      (MDSTs) as preclinical platforms for the assessment of personalized
      pharmacological therapies. Detailed molecular and phenotypic analyses revealed
      that MDSTs are the most heterogeneous group of genetically engineered mouse
      models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a
      mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with
      RAS/MAPK signaling activity, as expected from studies in xenografts and clinical
      trials providing validation of the utility of the model. Sensitivity of MDSTs to
      talazoparib, a poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitor,
      was predicted by PARP1 protein levels and by a new PARP sensitivity predictor
      (PSP) score developed from integrated analysis of drug sensitivity data of human
      cell lines. PSP score-based classification of The Cancer Genome Atlas breast
      cancer suggested that a subset of patients with limited therapeutic options would
      be expected to benefit from PARP-targeted drugs. These results indicate that
      MDSTs are useful models for studies of targeted therapies, and propose novel
      potential biomarkers for identification of breast cancer patients likely to
      benefit from personalized pharmacological treatments.

PMID- 28439538
TI  - Adaptive foveated single-pixel imaging with dynamic supersampling.
AB  - In contrast to conventional multipixel cameras, single-pixel cameras capture
      images using a single detector that measures the correlations between the scene
      and a set of patterns. However, these systems typically exhibit low frame rates,
      because to fully sample a scene in this way requires at least the same number of
      correlation measurements as the number of pixels in the reconstructed image. To
      mitigate this, a range of compressive sensing techniques have been developed
      which use a priori knowledge to reconstruct images from an undersampled
      measurement set. Here, we take a different approach and adopt a strategy inspired
      by the foveated vision found in the animal kingdom-a framework that exploits the
      spatiotemporal redundancy of many dynamic scenes. In our system, a high
      resolution foveal region tracks motion within the scene, yet unlike a simple
      zoom, every frame delivers new spatial information from across the entire field
      of view. This strategy rapidly records the detail of quickly changing features in
      the scene while simultaneously accumulating detail of more slowly evolving
      regions over several consecutive frames. This architecture provides video streams
      in which both the resolution and exposure time spatially vary and adapt
      dynamically in response to the evolution of the scene. The degree of local frame
      rate enhancement is scene-dependent, but here, we demonstrate a factor of 4,
      thereby helping to mitigate one of the main drawbacks of single-pixel imaging
      techniques. The methods described here complement existing compressive sensing
      approaches and may be applied to enhance computational imagers that rely on
      sequential correlation measurements.

PMID- 28439539
TI  - Imaging the dark emission of spasers.
AB  - Spasers are a new class of laser devices with cavity sizes free from optical
      diffraction limit. They are an emergent tool for various applications, including
      biochemical sensing, superresolution imaging, and on-chip optical communication.
      According to its original definition, a spaser is a coherent surface plasmon
      amplifier that does not necessarily generate a radiative photon output. However,
      to date, spasers have only been studied with scattered photons, and their
      intrinsic surface plasmon emission is a "dark" emission that is yet to be
      revealed because of its evanescent nature. We directly image the surface plasmon
      emission of spasers in spatial, momentum, and frequency spaces simultaneously. We
      demonstrate a nanowire spaser with a coupling efficiency to plasmonic modes of
      74%. This coupling efficiency can approach 100% in theory when the diameter of
      the nanowire becomes smaller than 50 nm. Our results provide clear evidence of
      the surface plasmon amplifier nature of spasers and will pave the way for their
      various applications.

PMID- 28439540
TI  - Climate legacies drive global soil carbon stocks in terrestrial ecosystems.
AB  - Climatic conditions shift gradually over millennia, altering the rates at which
      carbon (C) is fixed from the atmosphere and stored in the soil. However, legacy
      impacts of past climates on current soil C stocks are poorly understood. We used
      data from more than 5000 terrestrial sites from three global and regional data
      sets to identify the relative importance of current and past (Last Glacial
      Maximum and mid-Holocene) climatic conditions in regulating soil C stocks in
      natural and agricultural areas. Paleoclimate always explained a greater amount of
      the variance in soil C stocks than current climate at regional and global scales.
      Our results indicate that climatic legacies help determine global soil C stocks
      in terrestrial ecosystems where agriculture is highly dependent on current
      climatic conditions. Our findings emphasize the importance of considering how
      climate legacies influence soil C content, allowing us to improve quantitative
      predictions of global C stocks under different climatic scenarios.

PMID- 28439541
TI  - Potential energy-driven spin manipulation via a controllable hydrogen ligand.
AB  - Spin-bearing molecules can be stabilized on surfaces and in junctions with
      desirable properties, such as a net spin that can be adjusted by external
      stimuli. Using scanning probes, initial and final spin states can be deduced from
      topographic or spectroscopic data, but how the system transitions between these
      states is largely unknown. We address this question by manipulating the total
      spin of magnetic cobalt hydride complexes on a corrugated boron nitride surface
      with a hydrogen-functionalized scanning probe tip by simultaneously tracking
      force and conductance. When the additional hydrogen ligand is brought close to
      the cobalt monohydride, switching between a correlated S = 1/2 Kondo state, where
      host electrons screen the magnetic moment, and an S = 1 state with
      magnetocrystalline anisotropy is observed. We show that the total spin changes
      when the system is transferred onto a new potential energy surface that is
      defined by the position of the hydrogen in the junction. These results show how
      and why chemically functionalized tips are an effective tool to manipulate
      adatoms and molecules and a promising new method to selectively tune spin
      systems.

PMID- 28439542
TI  - CH3NH3PbI3 perovskites: Ferroelasticity revealed.
AB  - Ferroelectricity has been proposed as a plausible mechanism to explain the high
      photovoltaic conversion efficiency in organic-inorganic perovskites; however,
      convincing experimental evidence in support of this hypothesis is still missing.
      Identifying and distinguishing ferroelectricity from other properties, such as
      piezoelectricity, ferroelasticity, etc., is typically nontrivial because these
      phenomena can coexist in many materials. In this work, a combination of
      microscopic and nanoscale techniques provides solid evidence for the existence of
      ferroelastic domains in both CH3NH3PbI3 polycrystalline films and single crystals
      in the pristine state and under applied stress. Experiments show that the
      configuration of CH3NH3PbI3 ferroelastic domains in single crystals and
      polycrystalline films can be controlled with applied stress, suggesting that
      strain engineering may be used to tune the properties of this material. No
      evidence of concomitant ferroelectricity was observed. Because grain boundaries
      have an impact on the long-term stability of organic-inorganic perovskite
      devices, and because the ferroelastic domain boundaries may differ from regular
      grain boundaries, the discovery of ferroelasticity provides a new variable to
      consider in the quest for improving their stability and enabling their widespread
      adoption.

PMID- 28439543
TI  - Saving the injured: Rescue behavior in the termite-hunting ant Megaponera analis.
AB  - Predators of highly defensive prey likely develop cost-reducing adaptations. The
      ant Megaponera analis is a specialized termite predator, solely raiding termites
      of the subfamily Macrotermitinae (in this study, mostly colonies of
      Pseudocanthotermes sp.) at their foraging sites. The evolutionary arms race
      between termites and ants led to various defensive mechanisms in termites (for
      example, a caste specialized in fighting predators). Because M. analis incurs
      high injury/mortality risks when preying on termites, some risk-mitigating
      adaptations seem likely to have evolved. We show that a unique rescue behavior in
      M. analis, consisting of injured nestmates being carried back to the nest,
      reduces combat mortality. After a fight, injured ants are carried back by their
      nestmates; these ants have usually lost an extremity or have termites clinging to
      them and are able to recover within the nest. Injured ants that are forced
      experimentally to return without help, die in 32% of the cases. Behavioral
      experiments show that two compounds, dimethyl disulfide and dimethyl trisulfide,
      present in the mandibular gland reservoirs, trigger the rescue behavior. A model
      accounting for this rescue behavior identifies the drivers favoring its evolution
      and estimates that rescuing enables maintenance of a 28.7% larger colony size.
      Our results are the first to explore experimentally the adaptive value of this
      form of rescue behavior focused on injured nestmates in social insects and help
      us to identify evolutionary drivers responsible for this type of behavior to
      evolve in animals.

PMID- 28439544
TI  - Quantifying the negative impact of brain drain on the integration of European
      science.
AB  - The 2004/2007 European Union (EU) enlargement by 12 member states offers a unique
      opportunity to quantify the impact of EU efforts to expand and integrate the
      scientific competitiveness of the European Research Area (ERA). We apply two
      causal estimation schemes to cross-border collaboration data extracted from
      millions of academic publications from 1996 to 2012, which are disaggregated
      across 14 subject areas and 32 European countries. Our results illustrate the
      unintended consequences following the 2004/2007 enlargement, namely, its negative
      impact on cross-border collaboration in science. First, we use the synthetic
      control method to show that levels of European cross-border collaboration would
      have been higher without EU enlargement, despite the 2004/2007 EU entrants
      gaining access to EU resources incentivizing cross-border integration. Second, we
      implement a difference-in-difference panel regression, incorporating official
      intra-European high-skilled mobility statistics, to identify migration imbalance
      principally from entrant to incumbent EU member states-as a major factor
      underlying the divergence in cross-border integration between Western and Eastern
      Europe. These results challenge central tenets underlying ERA integration
      policies that unifying labor markets will increase the international
      competitiveness of the ERA, thereby calling attention to the need for effective
      home-return incentives and policies.

PMID- 28439545
TI  - Accelerated discovery of new magnets in the Heusler alloy family.
AB  - Magnetic materials underpin modern technologies, ranging from data storage to
      energy conversion to contactless sensing. However, the development of a new high
      performance magnet is a long and often unpredictable process, and only about two
      dozen magnets are featured in mainstream applications. We describe a systematic
      pathway to the design of novel magnetic materials, which demonstrates a high
      throughput and discovery speed. On the basis of an extensive electronic structure
      library of Heusler alloys containing 236,115 prototypical compounds, we filtered
      those displaying magnetic order and established whether they can be fabricated at
      thermodynamic equilibrium. Specifically, we carried out a full stability analysis
      of intermetallic Heusler alloys made only of transition metals. Among the
      possible 36,540 prototypes, 248 were thermodynamically stable but only 20 were
      magnetic. The magnetic ordering temperature, TC, was estimated by a regression
      calibrated on the experimental TC of about 60 known compounds. As a final
      validation, we attempted the synthesis of a few of the predicted compounds and
      produced two new magnets: Co2MnTi, which displays a remarkably high TC in perfect
      agreement with the predictions, and Mn2PtPd, which is an antiferromagnet. Our
      work paves the way for large-scale design of novel magnetic materials at
      potentially high speed.

PMID- 28439547
TI  - Tuning across the BCS-BEC crossover in the multiband superconductor Fe1+y Se x
      Te1-x : An angle-resolved photoemission study.
AB  - The crossover from Bardeen-Cooper-Schrieffer (BCS) superconductivity to Bose
      Einstein condensation (BEC) is difficult to realize in quantum materials because,
      unlike in ultracold atoms, one cannot tune the pairing interaction. We realize
      the BCS-BEC crossover in a nearly compensated semimetal, Fe1+y Se x Te1-x , by
      tuning the Fermi energy epsilonF via chemical doping, which permits us to
      systematically change Delta/epsilonF from 0.16 to 0.50, where Delta is the
      superconducting (SC) gap. We use angle-resolved photoemission spectroscopy to
      measure the Fermi energy, the SC gap, and characteristic changes in the SC state
      electronic dispersion as the system evolves from a BCS to a BEC regime. Our
      results raise important questions about the crossover in multiband
      superconductors, which go beyond those addressed in the context of cold atoms.

PMID- 28439546
TI  - Inositol polyphosphate multikinase promotes Toll-like receptor-induced
      inflammation by stabilizing TRAF6.
AB  - Toll-like receptor (TLR) signaling is tightly controlled to protect hosts from
      microorganisms while simultaneously preventing uncontrolled immune responses.
      Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a critical mediator
      of TLR signaling, but the precise mechanism of how TRAF6 protein stability is
      strictly controlled still remains obscure. We show that myeloid-specific deletion
      of inositol polyphosphate multikinase (IPMK), which has both inositol
      polyphosphate kinase activities and noncatalytic signaling functions, protects
      mice against polymicrobial sepsis and lipopolysaccharide-induced systemic
      inflammation. IPMK depletion in macrophages results in decreased levels of TRAF6
      protein, thereby dampening TLR-induced signaling and proinflammatory cytokine
      production. Mechanistically, the regulatory role of IPMK is independent of its
      catalytic function, instead reflecting its direct binding to TRAF6. This
      interaction stabilizes TRAF6 by blocking its K48-linked ubiquitination and
      subsequent degradation by the proteasome. Thus, these findings identify IPMK as a
      key determinant of TRAF6 stability and elucidate the physiological function of
      IPMK in TLR-induced innate immunity.

PMID- 28439548
TI  - Nonreciprocal charge transport in noncentrosymmetric superconductors.
AB  - Lack of spatial inversion symmetry in crystals offers a rich variety of physical
      phenomena, such as ferroelectricity and nonlinear optical effects (for example,
      second harmonic generation). One such phenomenon is magnetochiral anisotropy,
      where the electrical resistance depends on the current direction under the
      external magnetic field. We demonstrate both experimentally and theoretically
      that this magnetochiral anisotropy is markedly enhanced by orders of magnitude
      once the materials enter into a superconducting state. To exemplify this
      enhancement, we study the magnetotransport properties of the two-dimensional
      noncentrosymmetric superconducting state induced by gating of MoS2. These results
      indicate that electrons feel the noncentrosymmetric crystal potential much
      coherently and sensitively over the correlation length when they form Cooper
      pairs, and show open a new route to enhance the nonreciprocal response toward
      novel functionalities, including superconducting diodes.

PMID- 28439549
TI  - Observation of current-induced, long-lived persistent spin polarization in a
      topological insulator: A rechargeable spin battery.
AB  - Topological insulators (TIs), with their helically spin-momentum-locked
      topological surface states (TSSs), are considered promising for spintronics
      applications. Several recent experiments in TIs have demonstrated a current
      induced electronic spin polarization that may be used for all-electrical spin
      generation and injection. We report spin potentiometric measurements in TIs that
      have revealed a long-lived persistent electron spin polarization even at zero
      current. Unaffected by a small bias current and persisting for several days at
      low temperature, the spin polarization can be induced and reversed by a large
      "writing" current applied for an extended time. Although the exact mechanism
      responsible for the observed long-lived persistent spin polarization remains to
      be better understood, we speculate on possible roles played by nuclear spins
      hyperfine-coupled to TSS electrons and dynamically polarized by the spin-helical
      writing current. Such an electrically controlled persistent spin polarization
      with unprecedented long lifetime could enable a rechargeable spin battery and
      rewritable spin memory for potential applications in spintronics and quantum
      information.

PMID- 28439550
TI  - SAVI: Synthetic apertures for long-range, subdiffraction-limited visible imaging
      using Fourier ptychography.
AB  - Synthetic aperture radar is a well-known technique for improving resolution in
      radio imaging. Extending these synthetic aperture techniques to the visible light
      domain is not straightforward because optical receivers cannot measure phase
      information. We propose to use macroscopic Fourier ptychography (FP) as a
      practical means of creating a synthetic aperture for visible imaging to achieve
      subdiffraction-limited resolution. We demonstrate the first working prototype for
      macroscopic FP in a reflection imaging geometry that is capable of imaging
      optically rough objects. In addition, a novel image space denoising
      regularization is introduced during phase retrieval to reduce the effects of
      speckle and improve perceptual quality of the recovered high-resolution image.
      Our approach is validated experimentally where the resolution of various diffuse
      objects is improved sixfold.

PMID- 28439551
TI  - Single-layer nanosheets with exceptionally high and anisotropic hydroxyl ion
      conductivity.
AB  - When the dimensionality of layered materials is reduced to the physical limit, an
      ultimate two-dimensional (2D) anisotropy and/or confinement effect may bring
      about extraordinary physical and chemical properties. Layered double hydroxides
      (LDHs), bearing abundant hydroxyl groups covalently bonded within 2D host layers,
      have been proposed as inorganic anion conductors. However, typical hydroxyl ion
      conductivities for bulk or lamellar LDHs, generally up to 10-3 S cm-1, are
      considered not high enough for practical applications. We show that single-layer
      LDH nanosheets exhibited exceptionally high in-plane conductivities approaching
      10-1 S cm-1, which were the highest among anion conductors and comparable to
      proton conductivities in commercial proton exchange membranes (for example,
      Nafion). The in-plane conductivities were four to five orders of magnitude higher
      than the cross-plane or cross-membrane values of restacked LDH nanosheets. This
      2D superionic transport characteristic might have great promises in a variety of
      applications including alkaline fuel cells and water electrolysis.

PMID- 28439552
TI  - Direct observation of chiral currents and magnetic reflection in atomic flux
      lattices.
AB  - The prospect of studying topological matter with the precision and control of
      atomic physics has driven the development of many techniques for engineering
      artificial magnetic fields and spin-orbit interactions. Recently, the idea of
      introducing nontrivial topology through the use of internal (or external) atomic
      states as effective "synthetic dimensions" has garnered attraction for its
      versatility and possible immunity from heating. We engineer tunable gauge fields
      through the local control of tunneling phases in an effective two-dimensional
      manifold of discrete atomic momentum states. We demonstrate the ability to create
      homogeneous gauge fields of arbitrary value, directly imaging the site-resolved
      dynamics of induced chiral currents. Furthermore, we engineer the first
      inhomogeneous artificial gauge fields for cold atoms, observing the magnetic
      reflection of atoms incident upon a step-like variation of an artificial vector
      potential. These results open new possibilities for the study of topological
      phases and localization phenomena in atomic gases.

PMID- 28439553
TI  - Maximizing the performance of photothermal actuators by combining smart materials
      with supplementary advantages.
AB  - The search for higher-performance photothermal microactuators has typically
      involved unavoidable trade-offs that hinder the demonstration of ubiquitous
      devices with high energy density, speed, flexibility, efficiency, sensitivity,
      and multifunctionality. Improving some of these parameters often implies
      deterioration of others. Photothermal actuators are driven by the conversion of
      absorbed optical energy into thermal energy, which, by different mechanisms, can
      produce mechanical displacement of a structure. We present a device that has been
      strategically designed to show high performance in every metric and respond to
      optical radiation of selected wavelength bands. The device combines the large
      energy densities and sensitivity of vanadium dioxide (VO2)-based actuators with
      the wavelength-selective absorption properties of single-walled carbon nanotube
      (SWNT) films of different chiralities. SWNT coatings increased the speed of VO2
      actuators by a factor of 2 while decreasing the power consumption by
      approximately 50%. Devices coated with metallic SWNT were found to be 1.57 times
      more responsive to red light than to near-infrared, whereas semiconducting SWNT
      coatings resulted in 1.42 times higher responsivities to near-infrared light than
      to red light. The added functionality establishes a link between optical and
      mechanical domains of high-performance photoactuators and enables the future
      development of mechanical logic gates and electronic devices that are triggered
      by optical radiation from different frequency bands.

PMID- 28439554
TI  - Selective control of electron and hole tunneling in 2D assembly.
AB  - Recent discoveries in the field of two-dimensional (2D) materials have led to the
      demonstration of exotic devices. Although they have new potential applications in
      electronics, thermally activated transport over a metal/semiconductor barrier
      sets physical subthermionic limitations. The challenge of realizing an innovative
      transistor geometry that exploits this concern remains. A new class of 2D
      assembly (namely, "carristor") with a configuration similar to the metal
      insulator-semiconductor structure is introduced in this work. Superior
      functionalities, such as a current rectification ratio of up to 400,000 and a
      switching ratio of higher than 106 at room temperature, are realized by quantum
      mechanical tunneling of majority and minority carriers across the barrier. These
      carristors have a potential application as the fundamental building block of low
      power consumption electronics.

PMID- 28439556
TI  - Selective control of reconfigurable chiral plasmonic metamolecules.
AB  - Selective configuration control of plasmonic nanostructures using either top-down
      or bottom-up approaches has remained challenging in the field of active
      plasmonics. We demonstrate the realization of DNA-assembled reconfigurable
      plasmonic metamolecules, which can respond to a wide range of pH changes in a
      programmable manner. This programmability allows for selective reconfiguration of
      different plasmonic metamolecule species coexisting in solution through simple pH
      tuning. This approach enables discrimination of chiral plasmonic quasi
      enantiomers and arbitrary tuning of chiroptical effects with unprecedented
      degrees of freedom. Our work outlines a new blueprint for implementation of
      advanced active plasmonic systems, in which individual structural species can be
      programmed to perform multiple tasks and functions in response to independent
      external stimuli.

PMID- 28439555
TI  - Structural and biochemical differences between the Notch and the amyloid
      precursor protein transmembrane domains.
AB  - gamma-Secretase cleavage of the Notch receptor transmembrane domain is a critical
      signaling event for various cellular processes. Efforts to develop inhibitors of
      gamma-secretase cleavage of the amyloid-beta precursor C99 protein as potential
      Alzheimer's disease therapeutics have been confounded by toxicity resulting from
      the inhibition of normal cleavage of Notch. We present biochemical and structural
      data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD)
      that illuminate Notch signaling and that can be compared and contrasted with the
      corresponding traits of C99. The Notch-TMD and C99 have very different
      conformations, adapt differently to changes in model membrane hydrophobic span,
      and exhibit different cholesterol-binding properties. These differences may be
      exploited in the design of agents that inhibit cleavage of C99 while allowing
      Notch cleavage.

PMID- 28439557
TI  - Designer interphases for the lithium-oxygen electrochemical cell.
AB  - An electrochemical cell based on the reversible oxygen reduction reaction: 2Li+ +
      2e - + O2<-> Li2O2, provides among the most energy dense platforms for portable
      electrical energy storage. Such Lithium-Oxygen (Li-O2) cells offer specific
      energies competitive with fossil fuels and are considered promising for
      electrified transportation. Multiple, fundamental challenges with the cathode,
      anode, and electrolyte have limited practical interest in Li-O2 cells because
      these problems lead to as many practical shortcomings, including poor
      rechargeability, high overpotentials, and specific energies well below
      theoretical expectations. We create and study in-situ formation of solid
      electrolyte interphases (SEIs) based on bromide ionomers tethered to a Li anode
      that take advantage of three powerful processes for overcoming the most stubborn
      of these challenges. The ionomer SEIs are shown to protect the Li anode against
      parasitic reactions and also stabilize Li electrodeposition during cell recharge.
      Bromine species liberated during the anchoring reaction also function as redox
      mediators at the cathode, reducing the charge overpotential. Finally, the ionomer
      SEI forms a stable interphase with Li, which protects the metal in high Gutmann
      donor number liquid electrolytes. Such electrolytes have been reported to exhibit
      rare stability against nucleophilic attack by Li2O2 and other cathode reaction
      intermediates, but also react spontaneously with Li metal anodes. We conclude
      that rationally designed SEIs able to regulate transport of matter and ions at
      the electrolyte/anode interface provide a promising platform for addressing three
      major technical barriers to practical Li-O2 cells.

PMID- 28439558
TI  - CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes
      and mice.
AB  - Duchenne muscular dystrophy (DMD), caused by mutations in the X-linked dystrophin
      gene (DMD), is characterized by fatal degeneration of striated muscles. Dilated
      cardiomyopathy is one of the most common lethal features of the disease. We
      deployed Cpf1, a unique class 2 CRISPR (clustered regularly interspaced short
      palindromic repeats) effector, to correct DMD mutations in patient-derived
      induced pluripotent stem cells (iPSCs) and mdx mice, an animal model of DMD. Cpf1
      mediated genomic editing of human iPSCs, either by skipping of an out-of-frame
      DMD exon or by correcting a nonsense mutation, restored dystrophin expression
      after differentiation to cardiomyocytes and enhanced contractile function.
      Similarly, pathophysiological hallmarks of muscular dystrophy were corrected in
      mdx mice following Cpf1-mediated germline editing. These findings are the first
      to show the efficiency of Cpf1-mediated correction of genetic mutations in human
      cells and an animal disease model and represent a significant step toward
      therapeutic translation of gene editing for correction of DMD.

PMID- 28439559
TI  - Isolation of the simplest hydrated acid.
AB  - Dissociation of an acid molecule in aqueous media is one of the most fundamental
      solvation processes but its details remain poorly understood at the distinct
      molecular level. Conducting high-pressure treatments of an open-cage fullerene
      C70 derivative with hydrogen fluoride (HF) in the presence of H2O, we achieved an
      unprecedented encapsulation of H2O.HF and H2O. Restoration of the opening yielded
      the endohedral C70s, that is, (H2O.HF)@C70, H2O@C70, and HF@C70 in macroscopic
      scales. Putting an H2O.HF complex into the fullerene cage was a crucial step, and
      it would proceed by the synergistic effects of "pushing from outside" and
      "pulling from inside." The structure of the H2O.HF was unambiguously determined
      by single crystal x-ray diffraction analysis. The nuclear magnetic resonance
      measurements revealed the formation of a hydrogen bond between the H2O and HF
      molecules without proton transfer even at 140 degrees C.

PMID- 28439560
TI  - Direct 4D printing via active composite materials.
AB  - We describe an approach to print composite polymers in high-resolution three
      dimensional (3D) architectures that can be rapidly transformed to a new permanent
      configuration directly by heating. The permanent shape of a component results
      from the programmed time evolution of the printed shape upon heating via the
      design of the architecture and process parameters of a composite consisting of a
      glassy shape memory polymer and an elastomer that is programmed with a built-in
      compressive strain during photopolymerization. Upon heating, the shape memory
      polymer softens, releases the constraint on the strained elastomer, and allows
      the object to transform into a new permanent shape, which can then be
      reprogrammed into multiple subsequent shapes. Our key advance, the markedly
      simplified creation of high-resolution complex 3D reprogrammable structures,
      promises to enable myriad applications across domains, including medical
      technology, aerospace, and consumer products, and even suggests a new paradigm in
      product design, where components are simultaneously designed to inhabit multiple
      configurations during service.

PMID- 28439561
TI  - First detection of equatorial dark dust lane in a protostellar disk at
      submillimeter wavelength.
AB  - In the earliest (so-called "Class 0") phase of Sun-like (low-mass) star
      formation, circumstellar disks are expected to form, feeding the protostars.
      However, these disks are difficult to resolve spatially because of their small
      sizes. Moreover, there are theoretical difficulties in producing these disks in
      the earliest phase because of the retarding effects of magnetic fields on the
      rotating, collapsing material (so-called "magnetic braking"). With the Atacama
      Large Millimeter/submillimeter Array (ALMA), it becomes possible to uncover these
      disks and study them in detail. HH 212 is a very young protostellar system. With
      ALMA, we not only detect but also spatially resolve its disk in dust emission at
      submillimeter wavelength. The disk is nearly edge-on and has a radius of ~60
      astronomical unit. It shows a prominent equatorial dark lane sandwiched between
      two brighter features due to relatively low temperature and high optical depth
      near the disk midplane. For the first time, this dark lane is seen at
      submillimeter wavelength, producing a "hamburger"-shaped appearance that is
      reminiscent of the scattered-light image of an edge-on disk in optical and near
      infrared light. Our observations open up an exciting possibility of directly
      detecting and characterizing small disks around the youngest protostars through
      high-resolution imaging with ALMA, which provides strong constraints on theories
      of disk formation.

PMID- 28439562
TI  - Anomalous spin-orbit torque switching due to field-like torque-assisted domain
      wall reflection.
AB  - Spin-orbit torques (SOTs) allow the electrical control of magnetic states.
      Current-induced SOT switching of the perpendicular magnetization is of particular
      technological importance. The SOT consists of damping-like and field-like
      torques, and understanding the combined effects of these two torque components is
      required for efficient SOT switching. Previous quasi-static measurements have
      reported an increased switching probability with the width of current pulses, as
      predicted considering the damping-like torque alone. We report a decreased
      switching probability at longer pulse widths, based on time-resolved
      measurements. Micromagnetic analysis reveals that this anomalous SOT switching
      results from domain wall reflections at sample edges. The domain wall reflection
      was found to strongly depend on the field-like torque and its relative sign to
      the damping-like torque. Our result demonstrates a key role of the field-like
      torque in deterministic SOT switching and the importance of the sign correlation
      of the two torque components, which may shed light on the SOT switching
      mechanism.

PMID- 28439563
TI  - Mechanism of Vps4 hexamer function revealed by cryo-EM.
AB  - Vps4 is a member of AAA+ ATPase (adenosine triphosphatase associated with diverse
      cellular activities) that operates as an oligomer to disassemble ESCRT-III
      (endosomal sorting complex required for transport III) filaments, thereby
      catalyzing the final step in multiple ESCRT-dependent membrane remodeling events.
      We used electron cryo-microscopy to visualize oligomers of a hydrolysis-deficient
      Vps4 (vacuolar protein sorting-associated protein 4) mutant in the presence of
      adenosine 5'-triphosphate (ATP). We show that Vps4 subunits assemble into an
      asymmetric hexameric ring following an approximate helical path that sequentially
      stacks substrate-binding loops along the central pore. The hexamer is observed to
      adopt an open or closed ring configuration facilitated by major conformational
      changes in a single subunit. The structural transition of the mobile Vps4 subunit
      results in the repositioning of its substrate-binding loop from the top to the
      bottom of the central pore, with an associated translation of 33 A. These
      structures, along with mutant-doping experiments and functional assays, provide
      evidence for a sequential and processive ATP hydrolysis mechanism by which Vps4
      hexamers disassemble ESCRT-III filaments.

PMID- 28439564
TI  - The evolution of lifespan and age-dependent cancer risk.
AB  - The Armitage-Doll multi-stage model of carcinogenesis tremendously refocused
      cancer science by postulating that carcinogenesis is driven by a sequence of
      genetic changes in cells. Age-dependent cancer incidence thus has been explained
      in terms of the time necessary for oncogenic mutations to occur. While the multi
      step nature of cancer evolution is well-supported by evidence, the mutation
      centric theory is unable to explain a number of phenomena, such as the
      disproportion between cancer frequency and animal body size or the scaling of
      cancer incidence to animal lifespan. In this paper, we present a theoretical
      review of the current paradigm and discuss some fundamental evolutionary theory
      postulates that explain why cancer incidence is a function of lifespan and
      physiological, not chronological, aging.

PMID- 28439565
TI  - Shared temporoparietal dysfunction in dyslexia and typical readers with
      discrepantly high IQ.
AB  - It is currently believed that reading disability (RD) should be defined by
      reading level without regard to broader aptitude (IQ). There is debate, however,
      about how to classify individuals who read in the typical range but less well
      than would be expected by their higher IQ. We used functional magnetic resonance
      imaging (fMRI) in 49 children to examine whether those with typical, but
      discrepantly low reading ability relative to IQ, show dyslexia-like activation
      patterns during reading. Children who were typical readers with high-IQ
      discrepancy showed reduced activation in left temporoparietal neocortex relative
      to two control groups of typical readers without IQ discrepancy. This pattern was
      consistent and spatially overlapping with results in children with RD compared to
      typically reading children. The results suggest a shared neurological atypicality
      in regions associated with phonological processing between children with dyslexia
      and children with typical reading ability that is substantially below their IQ.

PMID- 28439566
TI  - Inflammatory Markers and Risk for Cognitive Decline in Chronic Kidney Disease:
      The CRIC Study.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is associated with an increased risk
      of cognitive decline, but the mechanisms remain poorly defined. We sought to
      determine the relation between serum inflammatory markers and risk of cognitive
      decline among adults with CKD. METHODS: We studied 757 adults aged >=55 years
      with CKD participating in the Chronic Renal Insufficiency Cohort Cognitive study.
      We measured interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, tumor
      necrosis factor (TNF)-alpha, high-sensitivity C-reactive protein (hs-CRP), and
      fibrinogen in baseline plasma samples. We assessed cognitive function at regular
      intervals in 4 domains and defined incident impairment as a follow-up score more
      than 1 SD poorer than the group mean. RESULTS: The mean age of the sample was
      64.3 +/- 5.6 years, and the mean follow-up was 6.2 +/- 2.5 years. At baseline,
      higher levels of each inflammatory marker were associated with poorer age
      adjusted performance. In analyses adjusted for baseline cognition, demographics,
      comorbid conditions, and kidney function, participants in the highest tertile of
      hs-CRP, the highest tertile of fibrinogen, and the highest tertile of IL-1beta
      had an increased risk of impairment in attention compared to participants in the
      lowest tertile of each marker. Participants in the highest versus lowest tertile
      of TNF-alpha had a lower adjusted risk of impairment in executive function. There
      was no association between other inflammatory markers and change in cognitive
      function. DISCUSSION: Among adults with CKD, higher levels of hs-CRP, fibrinogen,
      and IL-1beta were associated with a higher risk of impairment in attention.
      Higher levels of TNF-alpha were associated with a lower risk of impaired
      executive function.

PMID- 28439567
TI  - Sarcopenia, obesity, and mortality in US adults with and without chronic kidney
      disease.
AB  - INTRODUCTION: In pre-dialysis chronic kidney disease (CKD), the association of
      muscle mass with mortality is poorly defined, and no study has examined outcomes
      related to the co-occurrence of low muscle mass and excess adiposity (sarcopenic
      obesity). Methods: We examined abnormalities of muscle and fat mass in adult
      participants of the National Health and Nutrition Examination Survey 1999-2004.
      We determined whether associations of body composition with all-cause mortality
      differed between participants with CKD compared to those without. RESULTS: CKD
      modified the association of body composition with mortality (p=0.01 for
      interaction). In participants without CKD, both sarcopenia and sarcopenic obesity
      were independently associated with increased mortality compared with normal body
      composition (hazard ratio (HR) 1.44 (95%CI 1.07-1.93) and 1.64 (95%CI 1.26-2.13),
      respectively). These associations were not present among participants with CKD.
      Conversely, obese persons had the lowest adjusted risk of death, with an
      increased risk among those with sarcopenia (HR 1.43 (95%CI 1.05-1.95)) but not
      sarcopenic-obesity (p=0.003 for interaction by CKD status; HR 1.21 (95%CI 0.89
      1.65)), compared with obesity. CONCLUSION: Sarcopenia associates with increased
      mortality regardless of eGFR, but excess adiposity modifies this association
      among people with CKD. Future studies of prognosis and weight loss and exercise
      interventions in CKD patients should consider muscle mass and adiposity together
      rather than in isolation.

PMID- 28439568
TI  - Bariatric Surgery and Kidney-Related Outcomes.
AB  - The prevalence of severe obesity in both the general and the chronic kidney
      disease (CKD) populations continues to rise, with more than one-fifth of CKD
      patients in the United States having a body mass index of >=35 kg/m2. Severe
      obesity has significant renal consequences, including increased risk of end-stage
      renal disease (ESRD) and nephrolithiasis. Bariatric surgery represents an
      effective method for achieving sustained weight loss, and evidence from
      randomized controlled trials suggests that bariatric surgery is also effective in
      improving blood pressure, reducing hyperglycemia, and even inducing diabetes
      remission. There is also observational evidence suggesting that bariatric surgery
      may diminish the long-term risk of kidney function decline and ESRD. Bariatric
      surgery appears to be relatively safe in patients with CKD, with postoperative
      complications only slightly higher than in the general bariatric surgery
      population. The use of bariatric surgery in patients with CKD might help prevent
      progression to ESRD or enable selected ESRD patients with severe obesity to
      become candidates for kidney transplantation. However, there are also renal risks
      in bariatric surgery, namely, acute kidney injury, nephrolithiasis, and, in rare
      cases, oxalate nephropathy, particularly in types of surgery involving higher
      degrees of malabsorption. Although bariatric surgery may improve long-term kidney
      outcomes, this potential benefit remains unproved and must be balanced with
      potential adverse events.

PMID- 28439571
TI  - Four-year cross-sectional study of bleeding risk in dental patients on direct
      oral anticoagulants.
AB  - OBJECTIVE: New oral anticoagulants, or "direct oral anticoagulants" (DOACs), have
      been used worldwide in recent years. An evidence-based enigma regarding dental
      patients using DOACs still exists. METHOD AND MATERIALS: This was a 4-year, cross
      sectional study on individuals receiving DOAC therapy, treated in a single
      maxillofacial center. A bleeding event was the outcome parameter. Potential
      contributing risk factors were evaluated. RESULTS: Of a total of 111 patients, 72
      underwent a total of 305 oral procedures in 115 sessions. The overall frequency
      of bleeding events was 6.1% per session. One "major" (0.9%) and six "minor"
      (5.2%) events were recorded. The management was simple, local hemostasis.
      Statistically significant association was found between bleeding events and (1)
      history of spontaneous hemorrhage and (2) surgical procedures involving soft
      tissue manipulation. Withdrawal of DOAC therapy was not associated with decreased
      postoperative bleeding events. CONCLUSION: The risk of bleeding in dental
      patients using DOACs is low with no major consequences. The data support not
      stopping DOACs prior to dental treatment, regardless of the complexity or the
      extent of the procedure. Dosage adaptation is recommended in patients with a
      history of spontaneous hemorrhage.

PMID- 28439569
TI  - The Obesity Paradox in Kidney Disease: How to Reconcile it with Obesity
      Management.
AB  - Obesity, a risk factor for de novo chronic kidney disease (CKD), confers survival
      advantages in advanced CKD. This so-called obesity paradox is the archetype of
      the reverse epidemiology of cardiovascular risks, in addition to the lipid, blood
      pressure, adiponectin, homocysteine, and uric acid paradoxes. These paradoxical
      phenomena are in sharp contradistinction to the known epidemiology of
      cardiovascular risks in the general population. In addition to advanced CKD, the
      obesity paradox has also been observed in heart failure, chronic obstructive lung
      disease, liver cirrhosis, and metastatic cancer, as well as in the elderly. These
      are populations in whom protein-energy wasting and inflammation are strong
      predictors of early death. Both larger muscle mass and higher body fat provide
      longevity in these patients, whereas thinner body habitus and weight loss are
      associated with higher mortality. Muscle mass appears to be superior to body fat
      in conferring an even greater survival. The obesity paradox may be the result of
      a time discrepancy between competing risk factors, i.e., overnutrition as the
      long-term killer versus undernutrition as the short-term killer. Hemodynamic
      stability of obesity, lipoprotein defense against circulating endotoxins,
      protective cytokine profiles, toxin sequestration of fat mass, and antioxidation
      of muscle may play important roles. Despite claims that obesity paradox is a
      statistical fallacy and a result of residual confounding, the consistency of data
      and other causality clues suggest a high biologic plausibility. Examining the
      causes and consequences of the obesity paradox may help discover important
      pathophysiologic mechanisms leading to improved outcomes in patients with CKD.

PMID- 28439572
TI  - Long-term clinical and radiologic documentation of a maxillary odontogenic myxoma
      from early clinical signs to implant-supported prosthodontic rehabilitation: Case
      report and review of the literature.
AB  - Odontogenic myxoma (OM) is a non-metastasizing neoplasm of mesenchymal origin,
      arising in the tooth-bearing areas of the jaws. When regarding the whole spectrum
      of differential diagnoses for osteolytic jaw lesions, OM constitutes a benign
      tumor rarely located in the maxilla. Radiographically, displacement of teeth and
      frequent involvement of the sinus will be found with advanced maxillary OM. The
      tumor can be removed by means of several techniques, ranging from conservative
      measures to extended surgical procedures that differ according to type of bone
      resection and reconstruction of the defect. This report documents 10 years of
      follow-up in a patient suffering from a Type IV lesion of maxillary OM; with a
      radiographically proven growth extending into the right maxillary sinus, the
      patient underwent a segmental maxillectomy. After a tumor-free period of 5 years,
      the alveolar ridge splitting technique (ARST) was modified to insert dental
      implants into the horizontally deficient alveolar ridge of the maxilla, and final
      rehabilitation by means of a conditionally removable prosthetic reconstruction
      followed. In this paper, the most striking clinical signs of OM with which the
      dentist should be familiar are reviewed, and we discuss the advantages of
      segmental maxillectomy in case of an OM, along with the possibility of using
      ARST, aiming at prosthetic rehabilitation by placement of dental implants in
      cases of moderate alveolar ridge deficiency after tumor resection.

PMID- 28439570
TI  - Epigenomics of human CD8 T cell differentiation and aging.
AB  - The efficacy of the adaptive immune response declines dramatically with age, but
      the cell-intrinsic mechanisms driving immune aging in humans remain poorly
      understood. Immune aging is characterized by a loss of self-renewing naive cells
      and the accumulation of differentiated but dysfunctional cells within the CD8 T
      cell compartment. Using ATAC-seq, we inferred the transcription factor binding
      activities correlated with naive and central and effector memory CD8 T cell
      states in young adults. Integrating our results with RNA-seq, we identified
      transcription networks associated with CD8 T cell differentiation, with prominent
      roles implicated for BATF, ETS1, Eomes, and Sp1. Extending our analysis to aged
      humans, we found that the differences between the memory and naive subsets were
      largely preserved across age, but that naive and central memory cells from older
      individuals exhibited a shift toward more differentiated patterns of chromatin
      openness. Additionally, aged naive cells displayed a loss in chromatin
      accessibility at gene promoters, largely associated with a decrease in NRF1
      binding. This shift was implicated in a marked drop-off in the ability of the
      aged naive cells to transcribe respiratory chain genes, which may explain the
      reduced capacity of oxidative phosphorylation in older naive cells. Our findings
      identify BATF- and NRF1-driven gene regulation as potential targets for delaying
      CD8 T cell aging and restoring function.

PMID- 28439573
TI  - Systematic review of cyclosporin A-induced gingival overgrowth and genetic
      predisposition.
AB  - OBJECTIVE: This systematic review aimed to investigate the influence of gene
      polymorphisms on the development of gingival overgrowth in renal transplant
      patients treated with cyclosporin A. METHOD AND MATERIALS: Electronic and hand
      literature searches were conducted by two independent reviewers in MEDLINE
      Pubmed, Cochrane Library, ISI Web of Science, and SCOPUS Elsevier for prospective
      (case-control studies, cohort studies), cross-sectional, and retrospective
      studies published up to June 2016 (first week) in any language. Data were
      reviewed and extracted in duplicate independently. Methodologic quality
      assessment of the included studies was performed during the data extraction
      process. RESULTS: Due to the estimated high risk of bias and the heterogeneity of
      the included studies in regards to the variety of medications administered to
      study patients, a systematic review of the literature and not a meta-analysis of
      the data was performed. Fourteen articles meeting study inclusion criteria were
      selected for data extraction that examined the association between various
      genetic polymorphisms and gingival overgrowth in kidney transplant patients
      receiving cyclosporin A. Interleukin-1A, interleukin-10, transforming growth
      factor-beta1 and androgen receptor gene polymorphisms may have a significant
      effect on an individual susceptibility to cyclosporin A-induced gingival
      overgrowth in renal transplant patients. CONCLUSION: Genetic polymorphisms seem
      to affect the development of cyclosporin A-induced gingival overgrowth in renal
      transplant patients. Pharmacogenetics and pharmacogenomics have the potential to
      determine the clinical outcome of a medication, the drug efficacy, and adverse
      drug reactions such as gingival overgrowth.

PMID- 28439574
TI  - Randomized clinical trial on the efficacy of electric and manual toothbrushes in
      plaque removal and gingivitis control in visually impaired school students.
AB  - OBJECTIVE: To evaluate the efficacy of electric or manual toothbrushes in plaque
      removal and gingivitis control in visually impaired adolescents. METHOD AND
      MATERIALS: A randomized, controlled, examiner-blind crossover design was used in
      the study. Study subjects were 12- to 16-year-old visually impaired students from
      the School for the Blind in Guangzhou. Students in the test group used electric
      toothbrushes, whereas those in the control group used manual toothbrushes. The
      study consisted of two stages. Oral health status of the students was recorded at
      baseline, 2 weeks, and 4 weeks of each stage. In total, 42 visually impaired
      students were recruited in the study at baseline during the first stage. Quigley
      Hein Plaque Index (Q-H PI) and Loe and Silness Gingival Index (GI) were used. One
      way repeated measures analysis of variance followed by post hoc analysis was used
      to compare the mean Q-H PI and GI scores obtained at baseline, 2-week, and 4-week
      examinations between the test and control groups. RESULTS: In total, 33 subjects
      completed the study. No significant differences were noted between the two groups
      regarding Q-H PI and GI at baseline, whereas Q-H PI and GI values of the test
      group were significant reduced compared with those of the control group at 2
      weeks and 4 weeks (P < .001). CONCLUSION: An electric toothbrush reduced plaque
      and gingivitis more than manual toothbrushing among visually impaired school
      children.

PMID- 28439575
TI  - Polymerization Efficacy Affects the Long-term Mini-interfacial Fracture
      Toughness.
AB  - PURPOSE: To evaluate the effect of the type and concentration of photo-initiator
      on the long-term bonding efficacy to dentin in terms of mini-interfacial fracture
      toughness (mini-iFT). MATERIALS AND METHODS: The bonding efficacy of the one-step
      self-etch (SE) adhesive Clearfil S3 Bond Plus and four derivative experimental
      adhesives (Leuven University Bond [LUB]), which were similar in composition
      except for the (co)photo-initiators (all prepared by Kuraray Noritake),
      containing 2.0 wt% camphorquinone (CQ) and 2.0 wt% EDMAB (LUB-CQ/amine_high),
      0.35 wt% CQ and 0.35 wt% EDMAB (LUB-CQ/amine_low ), 2.0 wt% TPO (LUB-TPO_high),
      and 0.35 wt% TPO (LUB-TPO_low), was measured using a mini-iFT approach after
      being aged for 6 months and 1 year by water storage at 37 degrees C (control: 1
      week mini-iFT). The mini-iFT specimens were loaded until failure in a 4-point
      bending device to determine the interfacial fracture toughness (KIc). All
      fractured specimens were evaluated using scanning electron microscopy (SEM).
      RESULTS: The mini-iFT of Clearfil S3 Bond Plus and the adhesives with high photo
      initiator concentrations was not significantly different at 6 months, although it
      dropped significantly at 1 year. For each storage period, the mini-iFT of the
      adhesives with high photo-initiator concentrations was not significantly
      different from that of the commercial adhesive, in contrast to the significantly
      lower mini-iFT measured for adhesives with low concentrations of photo-initiator.
      SEM fracture analysis revealed that the adhesives with high concentrations of
      photo-initiator most frequently failed at the top of the hybrid layer at 1 week,
      while this failure pattern shifted to the bottom of the hybrid layer after aging.
      CONCLUSION: A one-step self-etch adhesive should contain photo-initiator in a
      sufficiently high concentration, as this directly improves its immediate and long
      term bonding efficacy to dentin. While the mini-iFT remained stable up to 6 month
      of aging for both the commercial and the adhesive with a high concentration of
      photo-initiator, the mini-iFT was found to decrease after 1 year of aging.

PMID- 28439576
TI  - Bond Strength to Eroded Enamel and Dentin Using a Universal Adhesive System.
AB  - PURPOSE: To evaluate the influence of previous acid etching on the bond strength
      of a self-etch universal adhesive system on sound and eroded enamel and dentin.
      MATERIALS AND METHODS: Flat enamel and dentin surfaces were obtained from bovine
      incisors (n = 44) and divided into two groups according to the exposure to
      erosive conditions: sound (without erosion) and eroded (after erosive challenge
      with 0.3% citric acid, pH 2.6, 5 min, 4x/day, 5 days). Each group was then
      divided into two subgroups (n = 11) according to the application or not of 37%
      phosphoric acid before applying a universal self-etch adhesive. Single Bond
      universal adhesive (3M ESPE) was applied and composite blocks were built up using
      Amelogen Plus (Ultradent). Sticks (1 * 1 mm) were obtained and the microtensile
      bond strength (uTBS) was assessed using a universal testing machine at a speed of
      1 mm/min. Data were analyzed with two-way ANOVA and Tukey's tests (p < 0.05).
      RESULTS: For enamel groups, significant differences were observed for erosive
      challenge (p = 0.034) and acid etching (p = 0.047), but not for the interaction
      between them (p = 0.182). The means +/- SD (MPa) for the erosive conditions were:
      sound, 25.02 +/- 5.82a; eroded, 28.45 +/- 5.92b; and for acid etching: without,
      24.89 +/- 5.39a; with, 28.58 +/- 6.23b (different superscript letters indicate
      significant differences). For dentin, both the erosive condition (p = 0.936) and
      acid pretreatment (p = 0.084), as well as their interaction (p = 0.107), did not
      affect the bond strength. CONCLUSION: The erosive challenge and previous acid
      etching significantly increased the bond strength of the tested universal
      adhesive to enamel but not to dentin.

PMID- 28439577
TI  - Shear Bond Strength of Lining Materials to Calcium-silicate Cements at Different
      Time Intervals.
AB  - PURPOSE: To compare the shear bond strength of three different light-curing,
      flowable composites (Ionoseal [IS], Vertise flow [VF], and Futurabond NR +
      Grandio Flow [GF]) on MTA-Angelus [MTA] or Biodentine [BD] at three different
      time intervals. MATERIALS AND METHODS: Freshly mixed MTA or BD was applied into
      180 identical plaster molds. Three minutes, 15 min, and 2 days after mixing,
      specimens of IS, VF, and GF with standardized size and diameter were applied on
      MTA and BD specimens (n = 10 per material and time interval). Subsequently, all
      specimens were stored at 36 degrees C and 100% humidity for 28 days. The shear
      bond strength was determined using a universal testing machine. Statistical
      evaluation was performed using multifactorial ANOVA and post-hoc Tukey's Test (p
      < 0.05). RESULTS: Multifactorial ANOVA did not show any significant influence of
      the combinations "lining material * time" (p = 0.257) and "calcium-silicate
      cement * lining material * time" (p = 0.241). Significant influences were
      detected for the interactions "calcium-silicate cement * lining material" (p =
      0.000) and "calcium-silicate cement * time" (p = 0.009) and for the parameters
      calcium-silicate cement (p = 0.000), lining material (p = 0.000), and time (p =
      0.008). The predominant failure mode of the restorative materials to the cement
      surfaces was mixed. CONCLUSION: Already 3 min after mixing, IS, VF, and GF
      achieved shear bond strengths on MTA or BD that were similar to those after 15
      min and 2 days.

PMID- 28439578
TI  - Long-Term Bond Strength of Self-Etch Adhesives to Normal and Artificially Eroded
      Dentin: Effect of Relative Humidity and Saliva Contamination.
AB  - PURPOSE: To investigate the effect of relative humidity and saliva contamination
      on short- and long-term bond strength of two self-etch adhesives to normal and
      artificially eroded dentin. MATERIALS AND METHODS: A total of 480 dentin
      specimens were produced from extracted human molars. Half of the specimens (n =
      240) were left untreated (normal dentin) whereas the other half (n = 240) were
      artificially eroded. The specimens were treated with Clearfil SE Bond (CSE) or
      Scotchbond Universal (SBU), and composite (Filtek Z250) was applied to the
      treated dentin surface under four experimental conditions: at a relative humidity
      of 45% or 85% without/with human saliva contamination. Shear bond strength (SBS)
      was measured after storage for 24 h (100% humidity; 37 degrees C) or 1 year (tap
      water; 37 degrees C). SBS results were statistically analyzed with a
      nonparametric ANOVA followed by Wilcoxon-Mann-Whitney tests (significance level:
      alpha = 0.05). RESULTS: SBS was significantly influenced by the dentin substrate
      (normal or artificially eroded dentin) and adhesive (p < 0.001) but not by
      relative humidity, saliva contamination, or storage. SBS significantly differed
      (all p < 0.001) following the ranking (MPa; medians [pooled]): SBU on normal
      dentin (21.1) > CSE on normal dentin (19.2) > SBU on artificially eroded dentin
      (17.1) > CSE on artificially eroded dentin (10.9). CONCLUSION: On normal dentin,
      the two self-etch adhesives showed stable bond strength over time even under
      adverse conditions such as high relative humidity and saliva contamination.
      However, erosively altered dentin had a detrimental effect on the bond strength
      of both the adhesives investigated.

PMID- 28439579
TI  - Severe Tooth Wear: European Consensus Statement ?on Management Guidelines.
AB  - This paper presents European expert consensus guidelines on the management of
      severe tooth wear. It focuses on the definition of physiological vs pathological
      tooth wear and recommends diagnosis, prevention, counseling, and monitoring aimed
      at elucidating the etiology, nature, rate and means of controlling pathological
      tooth wear. Management decisions are multifactorial, depending principally on the
      severity and effects of the wear and the wishes of the patient. Restorative
      intervention is typically best delayed as long as possible. When such
      intervention is indicated and agreed upon with the patient, a conservative,
      minimally invasive approach is recommended, complemented by supportive preventive
      measures. Examples of adhesive, minimum-intervention management protocols are
      presented.

PMID- 28439580
TI  - Editorial: Oral health promotion - not just lip service.

PMID- 28439581
TI  - Lower Educational Level is a Risk Factor for Tooth Loss - Analysis of a Swiss
      Population (KREBS Project).
AB  - PURPOSE: To analyse risk factors for tooth loss in women and men seeking
      treatment at the University of Basel, Switzerland. MATERIALS AND METHODS: Records
      of patients from the pool of patients at the department were consecutively
      screened between January 2009 and October 2011. Gender, smoking habits,
      education, profession, general health status and dental variables were recorded.
      Tooth loss was assessed on full-mouth periapical radiographs. Gender-nested
      logistic regression models were applied for statistical analysis. RESULTS: The
      sample consisted of 161 participants (4012 teeth in total, 3988 after exclusion
      of third molars), 80 women and 81 men, with a mean age of 48.0 +/- 14.6 in women
      and 47.7 +/- 12.5 in men. There were no significant differences in smoking status
      between men and women. Oral clinical data revealed similar gingival inflammation
      (BI) and number of sites with a periodontal probing depth (PPD) >= 5 mm among men
      and women. However, oral hygiene (PI) differed between men and women, with women
      having better oral hygiene (p < 0.01). Tooth loss increased from the front to the
      molar regions. A significant risk for tooth loss was associated with decreasing
      educational level. Compared to advanced education, individuals with 'no school
      graduation' showed a significantly higher risk for tooth loss in women (OR = 3.2,
      p = 0.02) and men (OR = 3.6, p = 0.03). Age >= 50 years significantly predicted
      tooth loss in men only (OR 2.2, p = 0.01). CONCLUSION: The results from the
      present study demonstrate lower educational level as a strong risk factor for
      tooth loss in this Swiss cohort. The educational level may need to be considered
      for diagnosis and treatment planning, and particularly for patient information
      practices to increase the patients' understanding of the development of oral
      diseases leading to tooth loss.

PMID- 28439582
TI  - Highly efficient Tsuji-Trost allylation in water catalyzed by Pd-nanoparticles.
AB  - Palladium nanoparticles stabilized by poly(vinylpyrrolidone) catalyze Tsuji-Trost
      allylations in water with very high turnover numbers. The di-allylation of
      methylene active compounds and the allylation of bio-based phenols was performed
      in high yield. The allylation of lignin showed a high selectivity towards the
      phenolic OH groups.

PMID- 28439583
TI  - Solution processing of chalcogenide materials using thiol-amine "alkahest"
      solvent systems.
AB  - Macroelectronics is a major focus in electronics research and is driven by large
      area applications such as flat panel displays and thin film solar cells.
      Innovations for these technologies, such as flexible substrates and mass
      production, will require efficient and affordable semiconductor processing. Low
      temperature solution processing offers mild deposition methods, inexpensive
      processing equipment, and the possibility of high-throughput processing. In
      recent years, the discovery that binary "alkahest" mixtures of ethylenediamine
      and short chain thiols possess the ability to dissolve bulk inorganic materials
      to yield molecular inks has lead to the wide study of such systems and the
      straightforward recovery of phase pure crystalline chalcogenide thin films upon
      solution processing and mild annealing of the inks. In this review, we recount
      the work that has been done toward elucidating the scope of this method for the
      solution processing of inorganic materials for use in applications such as
      photovoltaic devices, electrocatalysts, photodetectors, thermoelectrics, and
      nanocrystal ligand exchange. We also take stock of the wide range of bulk
      materials that can be used as soluble precursors, and discuss the work that has
      been done to reveal the nature of the dissolved species. This method has provided
      a vast toolbox of over 65 bulk precursors, which can be utilized to develop new
      routes to functional chalcogenide materials. Future studies in this area should
      work toward a better understanding of the mechanisms involved in the dissolution
      and recovery of bulk materials, as well as broadening the scope of soluble
      precursors and recoverable functional materials for innovative applications.

PMID- 28439584
TI  - Three-component nanorotors generated from fusion of complexes and post-fusion
      metal-metal exchange.
AB  - The fusion of two homoleptic complexes quantitatively created a novel three
      component nanorotor. The intra-supramolecular rotational dynamics leads to a
      rapid exchange (k298 = 24.0 +/- 2.5 kHz) of two degenerate Npy -> ZnPor
      interactions. Metal exchange at the remote HETTAP complexation site provided a
      faster nanorotor (k298 = 34.0 +/- 3.0 kHz).

PMID- 28439585
TI  - Controlled ring-opening polymerization of alpha-amino acid N-carboxy-anhydride by
      frustrated amine/borane Lewis pairs.
AB  - In this communication, we presented a novel strategy to control the ROP of alpha
      amino acid N-carboxy-anhydrides using the concept of frustrated Lewis pairs
      (FLPs). An FLP intermediate containing an interaction between the bulky borane
      Lewis acid and the amine groups of the propagation chain end is essential to
      accomplish the polypeptide synthesis with well-defined structures under mild
      conditions.

PMID- 28439586
TI  - Direct use of allylic alcohols and allylic amines in palladium-catalyzed allylic
      amination.
AB  - Allylic alcohols and allylic amines were directly utilized in a Pd-catalyzed
      hydrogen-bond-activated allylic amination under mild reaction conditions in the
      absence of any additives. The cooperative action of a Pd-catalyst and a hydrogen
      bonding solvent is most likely responsible for its high reactivity. The catalytic
      system is compatible with a variety of functional groups and can be used to
      prepare a wide range of linear allylic amines in good to excellent yields.
      Furthermore, this methodology can be easily applied to the one-step synthesis of
      two drugs, cinnarizine and naftifine, on a gram scale.

PMID- 28439587
TI  - A micron-scale laminar MAPbBr3 single crystal for an efficient and stable
      perovskite solar cell.
AB  - Nowadays, obtaining a thin and large-area perovskite single-crystal (SC) is still
      challenging. Herein, we report a novel strategy to prepare a laminar MAPbBr3 SC
      with a controllable thickness of 16 MUm and a size of 6 * 8 mm. Additionally, the
      SC solar cell achieves an intriguing efficiency of 7.11% with an impressive
      stability, maintaining 93% initial PCE after aging for 1000 h.

PMID- 28439588
TI  - Functional DNA-grafted supramolecular polymers - chirality, cargo binding and
      hierarchical organization.
AB  - The synthesis, characterization and functionalization of DNA-grafted
      supramolecular polymers are described. Cargo loading of the helical
      supramolecular assemblies with gold nanoparticles is demonstrated.

PMID- 28439589
TI  - Magnesium ion mobility in post-spinels accessible at ambient pressure.
AB  - We propose that Ti-containing post-spinels may offer a practically-accessible
      route to fast multivalent ion diffusion in close-packed oxide lattices, with the
      caveat that substantial thermodynamic driving forces for conversion reactions
      exist.

PMID- 28439590
TI  - Competition-based, quantitative chemical proteomics in breast cancer cells
      identifies new target profiles for sulforaphane.
AB  - Sulforaphane is a small molecule isothiocyanate which exhibits anticancer
      potential, yet its biological targets remain poorly understood. Here we employ a
      competition-based chemical proteomics strategy to profile sulforaphane's targets
      and identify over 500 targets along with their relative affinities. These targets
      provide a new set of mediators for sulforaphane's bioactivity, and aid
      understanding of its complex mode of action.

PMID- 28439591
TI  - Targeting secondary protein complexes in drug discovery: studying the
      druggability and chemical biology of the HSP70/BAG1 complex.
AB  - Proteins typically carry out their biological functions as multi-protein
      complexes, which can significantly affect the affinity of small-molecule
      inhibitors. HSP70 is an important target in oncology, so to study its chemical
      biology and the drug discovery potential of the HSP70/BAG1 complex, we designed a
      high-affinity non-nucleotide fluorescence polarisation probe.

PMID- 28439592
TI  - One-pot photoassisted synthesis, in situ photocatalytic testing for hydrogen
      generation and the mechanism of binary nitrogen and copper promoted titanium
      dioxide.
AB  - For the sustainable production of hydrogen by photocatalysis, the use of
      renewable resources such as water, organic compounds from plant biomass and earth
      abundant metal promoters is desired. We herein describe the previously not
      reported "one-pot" photoassisted synthesis of a binary metal-nitrogen promoted
      Cu(0)-N-TiO2 photocatalyst from a N-TiO2 precursor by photodeposition of copper
      directly in the photocatalytic suspension. The N-TiO2 contains nanocrystalline
      anatase as found by XRD and Raman spectroscopy. X-ray Photoelectron Spectroscopy
      (XPS) and Electron Spin Resonance (ESR) spectroscopy indicate that a nitrogen
      promoter is present as a substitutional site. The scheme of relaxation of a
      photoexcited charge through a substitutional nitrogen induced midgap states in N
      TiO2 is proposed. The binary promoted Cu(0)-N-TiO2 photocatalyst prepared from N
      TiO2 by "one-pot" photodeposition of copper in the suspension showed a high
      activity in the in situ hydrogen generation under near-UV/visible light with
      glycerol in water, up to 675 MUmol g-1 h-1. The "one-pot" photoassisted synthesis
      and mechanism of operation of the Cu(0)-N-TiO2 photocatalyst are studied by the
      complementary in situ spectroscopic methods.

PMID- 28439593
TI  - Reversible restructuring of supported Au nanoparticles during butadiene
      hydrogenation revealed by operando GISAXS/GIWAXS.
AB  - Periodically arranged, monodisperse gold nanoparticles supported on flat silicon
      substrates were studied for the hydrogenation of 1,3-butadiene under operando
      conditions using Grazing Incidence Small- and Wide-Angle X-ray Scattering
      (GISAXS/GIWAXS). It was found that the composition and shape of the nanoparticles
      depends very much on the chemical environment; the particles are shown to be
      dynamic, undergoing reversible size and shape change particularly during
      catalytic reaction, highlighting a dynamism often not observed in traditional
      studies. Specifically, the size of the Au nanoparticles increases during
      butadiene hydrogenation and this is attributed to the partial removal of a Au2O3
      at the metal-oxide interface and consequential shape change of the nanoparticle
      from a more hemispherical particle to a particle with a larger height to width
      ratio.

PMID- 28439594
TI  - The effect of chronotherapy on depressive symptoms. Evidence-based practice.
AB  - The global prevalence of depression is increasing, along with rates of depression
      associated disability and mortality, rendering depressive disorders a major
      public health issue. Chronotherapy involves a variety of strategies that control
      exposure to environmental stimuli that influence the biological clock, such as
      sleep deprivation (SD) or wake therapy (WT), sleep phase advance (SPA), and light
      and dark therapy (LT, DT). The purpose of this Evidence-Based Practice (EBP)
      paper is to answer PICOT questions by a review the effectiveness of
      chronotherapeutics interventions on depressive symptoms with depression and the
      depressive episode in the course of bipolar disorder. Early studies suggested the
      effectiveness of LT, SD, and SPA, more recent research has revealed differences
      in the efficacy of single and combined interventions involving both
      chronotherapeutic and pharmacological components. This therapy reduced dura-tion
      of hospitalization, improvement recovery, and reduced for changes in drug
      prescriptions.

PMID- 28439596
TI  - Comparative clinical study of laparoscopic and open surgery in children with
      choledochal cysts.
AB  - OBJECTIVES: To investigate the safety and effectiveness of laparoscopic
      management of choledochal cysts compared with the open approach, even in early
      childhood.  Methods: We conducted a retrospective study of 206 patients with
      choledochal cysts between June 2003 and May 2015. Of these, 104 patients
      underwent open cyst excision and hepaticojejunostomy (open operation [OP]) and
      102 patients received laparoscopic management and hepaticojejunostomy
      (laparoscopic operation [LP]). The patients who underwent a laparoscopic approach
      were further divided by the age of 3 years. We compared patients' perioperative
      and follow-up conditions between the 2 approaches and the 2 age groups.  Results:
      All patients were cured with no incidence of mortality. The operating time was
      significantly longer in the LP (OP: 225.4+/-51.0 min versus LP: 170.3+/-35.4 min,
      p=0.000), but blood loss (LP: 12.9+/-22.9 ml versus OP: 32.4+/-52.7 ml, p=0.001)
      was significantly larger in the OP. The number of days to normal oral feeding
      (LP: 3.3+/-0.9 dyas versus OP: 4.1+/-0.9 days, p=0.000) and postoperative stay-in
      ward duration (LP: 7.5+/-2.7 days versus OP: 9.6+/-5.5 days, p=0.001) were
      significantly shorter with the LP. There were no significant differences among
      all of the above tests between the younger and older patients (p greater than
      0.05). Conclusions: Laparoscopic operation is safe and effective, even for young
      children. With the advantages of less blood loss, smaller trauma, shorter
      postoperative recovery time, and improved cosmetic features, it is worth
      considering its widespread application.

PMID- 28439595
TI  - The association between pain and sleep in fibromyalgia.
AB  - OBJECTIVE: To clarify the association between pain and sleep in fibromyalgia. 
      Methods: Electronic databases, including PsycINFO, the Cochrane database for
      systematic reviews, PubMed, EMBASE, and Ovid were searched to identify eligible
      articles. Databases independently screened and  the quality of evidence using a
      reliable and valid quality assessment tool was assessed.  Results: In total, 16
      quantitative studies fulfilled the inclusion criteria. According to the results,
      increased pain in fibromyalgia was associated with reduced sleep quality,
      efficiency, and duration and increased sleep disturbance and onset latency and
      total wake time. Remarkably, depressive symptoms were also related to both pain
      and sleep in patients with fibromyalgia.   Conclusion: Management strategies
      should be  developed to decrease pain while increasing sleep quality in patients
      with fibromyalgia. Future studies should also consider mood disorders and
      emotional dysfunction, as comorbid conditions could occur with both pain and
      sleep disorder in fibromyalgia.

PMID- 28439597
TI  - Ambu AuraOnce versus i-gel laryngeal mask airway in infants and children
      undergoing surgical procedures. A randomized controlled trial.
AB  - OBJECTIVES: To compare the efficacy and performance of the pediatric Ambu
      AuraOnce (Ambu AO) mask (Ambu, Copenhagen, Denmark) and i-gel mask (Intersurgical
      Ltd., Wokingham, United Kingdom). Methods: From May 2015 to September 2016, 112
      patients, 0-14 years old, underwent elective surgery at a tertiary university
      hospital (Riyadh, Saudi Arabia). They were randomly assigned to the Ambu AO or i
      gel group. Three groups underwent a subgroup analysis: <=5 kg (group 1), 5.1-10.0
      kg (group 2), and >10 kg (group 3). Results: The oropharyngeal leak pressure was
      significantly higher for the i-gel (25.4+/-4.1 cm H2O) than for the Ambu AO
      (22.5+/-3.9 cm H2O, p less than 0.001). The Ambu AO had a slightly higher ease of
      insertion compared to the i-gel (100% versus 94%, p=0.08)  and required less
      manipulation (2% versus 11%, p=0.07).The Ambu AO and i-gel showed non-significant
      differences in performance between weight groups. There were statistically
      significant differences for higher leak pressure in group 2 (p=0.01) and group 3
      (p=0.002) in favor of the i-gel, and for less manipulation in the Ambu AO in
      group 1 (p=0.04). Fiberoptic viewing was superior in group 2 for the i-gel
      (p=0.03) and in group 3 for the Ambu AO (p=0.02). Conclusion: Both devices
      demonstrated equally good performance with low morbidity. The Ambu AO had a
      statistical tendency towards easier insertion and less manipulation. Confirming
      this finding will require large scale trials.

PMID- 28439598
TI  - Does pulmonary rehabilitation alleviate depression in older patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVES: To identify if pulmonary rehabilitation can achieve a clinically
      significant alleviation in the level of depression among chronic obstructive
      pulmonary disease (COPD) patients older than 70 years.  Methods: We conducted a
      retrospective secondary analysis of the patients' electronic records from a major
      pulmonary rehabilitation center in Cleveland, OH, United States between 2010 and
      2014. Profiles of 105 participants who had completed more than 6 pulmonary
      rehabilitation sessions and were older than 70 years at the time of enrollment in
      the program were included. The Beck Depression Inventory scores at the baseline
      and the end of the pulmonary rehabilitation sessions were compared.    Results:
      There was a statistically and clinically significant reduction in mean scores of
      depression from the baseline to the end of pulmonary rehabilitation: mean+/-SD:
      104+/-5.6; p=0.00. The mean+/-SD depression score at the end was 9+/-4.3 compared
      with the baseline 17+/-7.8. Seventy-seven (73%) participants showed clinically
      significant improvement in depression; however, 20 participants (27%) had no
      clinically significant improvement, and 8 (8%) had worse depression at the end of
      pulmonary rehabilitation. Participants with higher depression scores at the
      baseline were 1.3 times more likely to achieve clinically significant alleviation
      in depression at the end of rehabilitation (odds ratio = 1.3, p=0.00). 
      Conclusion: Pulmonary rehabilitation induced clinically significant alleviation
      in depression among participants with COPD aged over 70 years.

PMID- 28439599
TI  - Agreement of histopathological findings of uterine curettage and hysterectomy
      specimens in women with abnormal uterine bleeding.
AB  - OBJECTIVES: To examined the diagnostic value of  dilatation and curettage (D and
      C) in patients with abnormal uterine bleeding (AUB) by conducting a
      histopathological examination of endometrial tissues by D and C and hysterectomy.
      Methods: In this retrospective study, the medical records of 163 women who had
      been hospitalized  in the Obstetrics and Gynecology Ward, Amir-al-Momenin
      Hospital, Semnan, Iran between 2010 and 2015 for diagnostic curettage due to  AUB
      and who had undergone hysterectomy were investigated. The patients'
      characteristics and histopathologic results of curettage and hysterectomy were
      extracted, and sensitivity and specificity and positive and negative predictive
      values of curettage were calculated. Results: The mean +/- standard deviation age
      of the patients was 49.8+/-7.8 years. The sensitivity values of D and C in the
      diagnosis of endometrial pathologies was 49.1%, specificity 84.5%, positive
      60.5%, and negative predictive 77.5%. The sensitivities of D and C in the
      diagnosis of various endometrial hyperplasia was 62.5%, disordered proliferative
      endometrium 36.8%, and endometrial cancer 83.3%. Of 6 patients with endometrial
      polyps on performing hysterectomy, no patient was diagnosed by curettage.
      Conclusions: Dilatation and curettage has acceptable sensitivity in the diagnosis
      of endometrial cancer, low sensitivity in the diagnosis of endometrial
      hyperplasia, and very low sensitivity in the diagnosis of disordered
      proliferative endometrium and endometrial polyps.

PMID- 28439600
TI  - Factors affecting pregnancy weight gain and relationships with maternal/fetal
      outcomes in Turkey.
AB  - OBJECTIVES: To determine the effects of pre-pregnancy body mass index (BMI) and
      gestational weight gain on maternal and fetal complications, and to examine
      whether Turkish women achieve the recommended gestational weight gain. We also
      investigated the relationship between pregnancy weight gain and mode of delivery,
      with an examination of maternal anthropometry.  Methods: A retrospective cross
      sectional study was conducted on a population of 986 pregnant women between
      November 2011 and November 2015 at Ataturk Education and Research Hospital,
      Ankara, Turkey. Maternal age, BMI, monthly weight gain during pregnancy, infant
      birth weight, gender, and maternal and fetal adverse outcomes were evaluated.
      Results: The frequency of maternal complications was positively associated with
      elevated pre-pregnancy BMI (p less than 0.05), and weight gain during pregnancy
      was associated with parity and increased infant birth weight (p less than 0.05).
      However, no correlations were observed between mean pregnancy weight gain and
      maternal complications (p greater than 0.05). The percentage of women who gained
      the Institute of Medicine (IOM)-recommended amount of weight was the highest in
      the underweight BMI group (54.1%) and the lowest in the obese BMI group (24.3%).
      Pregnancy weight gain exceeded IOM recommendations in the overweight (56.3%) and
      obese (52.5%) groups. Conclusions: While maternal weight gain during pregnancy
      affects neonatal body weight, higher pre-pregnancy BMI has an adverse effect on
      recommended weight gain during pregnancy, with increased maternal complications.

PMID- 28439601
TI  - Collapsing glomerulopathy, the Saudi Arabian scenario. A study of 31 cases and a
      review of literature.
AB  - OBJECTIVES: To compare the clinico-pathological features of collapsing
      glomerulopathy (CG) at a tertiary hospital in Saudi Arabia with the world
      literature. Methods: In a retrospective study, all biopsy-diagnosed cases of CG
      between 2004-2015 were identified and analyzed, at King Khalid University
      Hospital, King Saud University, Riyadh. The clinico-pathological findings along
      with prognosis were reviewed and compared with the reported literature.  Results:
      Thirty-one CG patients were identified, most were adult males. All the CG cases
      were idiopathic, all Arabs, none HIV positive, none of African descent, and none
      with a history of drug abuse. The number of glomeruli with collapsing lesions per
      biopsy ranged from 1 to 9. Other types of FSGS lesions (not otherwise specified
      and perihilar) were also noted. There was extensive podocyte effacement. Upon
      treatment, remission (complete/partial) was noted in almost half the patients;
      around one fourth did not respond to treatment; and one fourth progressed to end
      stage kidney disease (ESKD). The median time taken to develop ESKD from the time
      of biopsy diagnosis was 23 months. Conclusion: The clinico-pathological and
      prognostic correlates of CG in Saudi Arabia are comparable with that of the world
      literature. The management protocol at our center is the same as that practiced
      in different parts of the world, and the prognosis is overall poor.

PMID- 28439602
TI  - Antibiogram profile of septic meningitis among children in Duhok, Iraq.
AB  - OBJECTIVES:   To determine the prevalence of bacteria in the cerebrospinal fluid
      (CSF), and the antibiogram profile in pediatric patients with suspected
      meningitis. Methods: This descriptive study was conducted between January 2014
      and January 2016 in the Hevi Paediatric Teaching Hospital in Duhok, Iraq. The CSF
      samples were withdrawn from 432 pediatric patients suspected of meningitis. The
      samples were cultured, and antibiotic sensitivity tests were performed.  Results:
      There were 33 (7.6%) culture positive cases among 432 CSF samples. Among the
      positives cases, there were 18 culture positive for Streptococcus pneumoniae (S.
      pneumoniae). There were 4 cases of Viridans streptococci. In addition, there were
      2 cases each of Escherichia coli (E. coli), Klebsiella pneumoniae (K.
      pneumoniae), and Non-coagulase staphylococci. There was only one case each of
      Staphylococcus aureus, Streptococcus pyogenes, Enterococcus species, Haemophilus
      influenzae, and Pseudomonas aeruginosa (P. aeruginosa). The isolated S.
      pneumoniae strains showed 47% sensitivity against penicillin, 13% against
      cefotaxime, but 100% of sensitivity against vancomycin. Isolates of gram-negative
      bacilli (E. coli, K. pneumoniae, and P. aeruginosa) were 100% sensitive to
      imipenem and amikacin, but had 0% sensitivity to cefotaxime and vancomycin. All
      isolates of Staphylococci were sensitive to vancomycin, gentamicin, and
      clindamycin but were resistant to penicillin and cefotaxime. Conclusion:
      Streptococcus pneumoniae is currently the leading cause of meningitis among
      children in Duhok city. The antimicrobial resistance pattern indicates that all
      isolates of S. pneumoniae were sensitive to vancomycin.

PMID- 28439603
TI  - Emergence of Stenotrophomonas maltophilia nosocomial isolates in a Saudi
      children's hospital. Risk factors and clinical characteristics.
AB  - OBJECTIVES:   To describe the clinical characteristics of pediatric patients
      colonized or infected by Stenotrophomonas maltophilia (S. maltophilia) at a Saudi
      children's hospital, to identify risk factors associated with infection, and to
      investigate the antimicrobial resistance patterns of this emerging pathogen. 
      Methods: In this cross-sectional observational study, 64 non-duplicating S.
      maltophilia strains were isolated  in Najran Maternity and Children's Hospital,
      Najran,  Saudi Arabia between January 2015 to February 2016. Antimicrobial
      susceptibility testing was performed using the reference broth microdilution
      method.  Results: In this study, 48 (75%) isolates were identified in true
      infections and 16 (25%) isolates were considered colonization. The main types of
      S. maltophilia infection were pneumonia in 22 (45.8%) patients and bloodstream
      infection in 14 (29.2%) patients. The significant risk factors included exposure
      to invasive procedure (p=0.02), and presence of acute leukemia as an underlying
      disease (p=0.02). The most active antimicrobials were
      trimethoprim/sulfamethoxazole (100% sensitivity) and tigecycline (93.7%
      sensitivity). Conclusions: Stenotrophomonas maltophilia is an emerging nosocomial
      pathogen among pediatric patients. Accurate identification and susceptibility
      testing of this emerging pathogen are crucial for the management of infected
      patients and prevention of spread of this nosocomial pathogen.

PMID- 28439604
TI  - Emergency presentation of colorectal cancer in Northwestern Saudi Arabia.
AB  - OBJECTIVES: To investigate the frequency and clinical characteristics of
      emergency presentation of colorectal carcinoma (CRC) in Tabuk Region of Saudi
      Arabia.  Methods: This is a retrospective, descriptive hospital-based study. All
      cases with CRC that presented to the main referral hospitals in Tabuk, Saudi
      Arabia between 2010 and 2015 were retrieved. The relevant hospitals are: King
      Salman Military Hospital, King Khalid Hospital, and King Fahad Hospital. 
      Results: Seventy-three patients were included in the study. Twenty-two patients
      presented emergency constituting 30.6% of the total. Emergency CRC presentation
      was more common in elderly patients (81.8%), but a greater proportion of young
      patients was also affected (40% versus 29% in elderly patients). The disease is
      more common in females (37%) than males (26.7%) and intestinal obstruction was
      the sole form of presentation. Patients presenting emergency had more right-sided
      (61.9%) than left-sided tumors (30.2%). Advanced presentation with metastasis was
      noted in 40% of the patients presenting acutely. Conclusion: Emergency CRC
      presentation is common in the Tabuk region. Patients tend to present at an
      advanced stage, which necessitates an endeavor to detect the disease in its early
      stages, possibly through initiation of health education programs and suitable
      screening projects.

PMID- 28439605
TI  - Effectiveness of a preparatory aid in facilitating oral assessment in a group of
      Saudi children with autism spectrum disorders in Central Saudi Arabia.
AB  - OBJECTIVES: To evaluate the effectiveness of a specially-designed dental book
      (preparatory aid) on the behavior of a group of Autism Spectrum Disorder (ASD)
      Saudi children during their first dental visit to the College of Dentistry, King
      Saud University, Riyadh, Saudi Arabia. Methods: A cross-sectional double-blinded
      pre-and post clinical study consisting of 2 parts; a survey targeting the
      parents, and a clinical oral examination of their ASD children was conducted
      between January and June of 2016.  Results: A total of 40 children (75% males and
      25% females) with an average age of 6.1 years were included. Approximately 47.5%
      children acted positively during the dental procedure. The dental book had a
      positive effect on the behavior of 37.5%  children according to their parents'
      evaluation and highly effective in enhancing the parents' dental knowledge
      (67.5%).  Conclusion: Parents expressed positive opinions regarding the use of
      preparatory aids in the dental environment. Approximately half of the ASD
      children benefit from the preparatory aid used according to the parents' opinion,
      and the follow up survey showed improvement in the parent's dental knowledge and
      oral hygiene practices.

PMID- 28439606
TI  - Cemento-ossifying fibroma of the mandible. A clinicopathological report.
AB  - Cemento-ossifying fibromas are rare fibro-osseous benign neoplasms that affect
      the jaws. They are included in the group of mesodermal odontogenic tumors and
      commonly present as a progressively growing lesion that might attain enormous
      size with resultant deformity, if left untreated. A confusion prevails on the
      terminology, which can only be confirmed by histopathologic evaluation. A case of
      cemento-ossifying fibroma involving the right mandible is described in a 30 year
      old female patient. The clinical, radiographic, histologic features are presented
      and the various differential diagnosis are discussed.

PMID- 28439607
TI  - Late metastatic endometrial carcinoma at the repair site of an abdominal wall
      incisional hernia.
AB  - The abdominal wall is a very rare site for endometrial cancer metastases. Its
      appearance generally indicates advanced cancer with poor prognosis. We report a
      case of a 55-year-old female who presented with an incisional hernia 4 years
      after abdominal panhysterectomy for endometrioid adenocarcinoma in 2009. Open
      hernia mesh repair was performed but on follow-up, she complained of pain and a
      swelling at the repair site. This was radiologically diagnosed as fibromatosis,
      but tru-cut biopsy confirmed presence of fibromatosis as well as a metastatic
      endometrial carcinoma. She was started on neoadjuvant chemotherapy, but had poor
      response, and therefore, radical excision was performed. She remained well with
      no metastatic recurrence at 12-month follow-up. This case illustrates late
      appearance of abdominal wall metastasis from abdomino-pelvic malignancies and
      highlights the need to exclude the presence of recurrence or metastases prior to
      surgical repair of incisional hernia occurring after the resection of abdominal
      or pelvic malignancy.

PMID- 28439608
TI  - Isolation of Mycoplasma genitalium from endocervical swabs of infertile women.
AB  - OBJECTIVES: To determine the occurrence of Mycoplasma genitalium (M. genitalium)
      infection in infertile women attending infertility clinic and its association to
      infertility. Methods: Endocervical specimens were collected from women presenting
      with primary and secondary infertility and from fertile women as control group.
      Real-time polymerase chain reaction (PCR)  assay was performed to detect the
      presence of M. genitalium from these endocervical specimens.  Results: Mycoplasma
      genitalium was detected in 3% of infertile women. There was no statistically
      significant difference between infertility and control group as to signs and
      symptoms except for signs of cervicitis were presented only among infertile
      group. We found no significant differences among fertile and infertile women for
      M. genitalium infection. Conclusion: An association between M. genitalium
      infection and infertility may exist. Screening of women for M. genitalium
      infection is recommended as part of investigations for infertility.

PMID- 28439609
TI  - Primary care physicians' knowledge of sleep medicine and barriers to transfer of
      patients with sleep disorders. A cross-sectional study.
AB  - OBJECTIVES: To assess primary care physicians' (PCPs) knowledge and attitudes
      toward sleep disorders.  Methods: In this cross-sectional quantitative study, we
      surveyed 88 primary care centers under the Ministry of Health during 2015 in
      Riyadh, Saudi Arabia, using a combination of pre-designed validated
      questionnaires. Knowledge was assessed using the Assessment of Sleep Knowledge in
      Medical Education (ASKME) questionnaire, and attitude was assessed using a pre
      designed survey. For numerical variables, t-test was used, and for categorical
      variables, Chi-square test was used. Results: Data from 223 PCPs (males 50.2%)
      were analyzed. Among the participants, 44 (19.9%) did not know that sleep
      medicine is a distinct medical specialty, and 24 (10.9%) felt that sleep
      disorders are uncommon medical problems based on their daily practice. Only 87
      (39%) of physicians stated that they referred patients with sleep disorders to
      specialized medical centers for further management. The mean score of the ASKME
      questionnaire was 14.4 +/- 4 out of 30 (48%). The majority of physicians (78.5%)
      obtained a score between 11 and 20. Score results were not related to gender or
      years of practice. Conclusion: Primary care physicians' have a low level of
      awareness and poor knowledge of sleep medicine and sleep disorders.

PMID- 28439610
TI  - Phase down of amalgam. Awareness of Minamata convention among Jordanian dentists.
AB  - [No Abstract Available].

PMID- 28439611
TI  - The Saudi clinical practice guideline for the prophylaxis of venous
      thromboembolism in long-distance travelers.
AB  - [No Abstract Available].

PMID- 28439612
TI  - [Imaging of the paranasal sinuses and anterior skull base].
AB  - Due to the complex anatomy of the anterior skull base and paranasal sinuses,
      radiologic diagnostics in this area are challenging. Magnetic resonance imaging
      (MRI) and computed tomography (CT) are the primary indicated modalities.
      Guidelines helping to select the appropriate modality have been published by the
      German Society of Head and Neck Radiology and the Society of Otorhinolaryngology.
      The present article presents an overview of the current radiologic procedures and
      their optimized implementation using clinical examples. These examples highlight
      the fact that a combination of at least CT and MRI is frequently required. Use of
      CT for intraoperative navigation is everyday practice in clinical routine.
      Occasionally, additional procedures such as angiography or myelography are
      necessary, particularly in cases of preoperative vascular diagnostics or
      embolization. Overall, evaluation of radiologic diagnostics in this area is
      complex; it requires experience and knowledge of the disease, as well as an
      understanding of the diagnostic procedures. Close collaboration between head and
      neck surgeons and radiologists is thus essential.

PMID- 28439613
TI  - The role of delayed head CT in evaluation of elderly blunt head trauma victims
      taking antithrombotic therapy.
AB  - INTRODUCTION: Increasing active longevity has created an increasing surge of
      elderly trauma patients. The majority of these patients suffer blunt trauma and
      many are taking antithrombotic agents. The literature is mixed regarding the
      utility of routine repeat head CT in patients taking antithrombotic medications
      with a GCS of 15 and initial negative head CT. We hypothesized that scheduled
      delayed CT head 12 h after admission (D-CTH) in elderly blunt trauma victims
      would not identify clinically significant new hemorrhages or change management.
      METHODS: A retrospective chart review using our institutional trauma registry of
      patients >=65 years sustaining blunt head injuries from 2010 to 2012 was
      performed. By hospital protocol, all such patients on antithrombotic therapy
      receive a routine D-CTH. All of these patients were included. Demographics,
      injuries, medications, laboratory values, LOS, mental status, and management were
      analyzed. RESULTS: Of the 234 patients meeting inclusion criteria, 8 initially
      were identified as having D-ICH. Upon further review, five patients had the same
      findings on both initial and delayed CT scans and one patient was determined to
      actually have had a hemorrhage stroke. Ultimately, only two patients (0.85%, 95%
      CI 0.1-3.1%) had new ICH discovered on D-CTH. None of the patients on warfarin
      demonstrated any new injury on D-CTH (95% CI <= 4.6%). Only one patient taking
      aspirin as a sole agent had a delayed injury on D-CTH (1.1%, 95% CI 0-4.2%). The
      remaining patient was taking a combination of aspirin and clopidogrel
      representing 2.2% of 45 patients on combination therapy (95% CI 0.1-11.8%). Only
      two patients taking a direct thrombin inhibitor (dabigatran) met inclusion
      criteria and neither endured a bleed (95% CI <= 77.6%). Further analysis revealed
      no cases with clinical changes or surgical intervention for new ICH on delayed
      imaging. No inference could be made to predict which patients would suffer D-ICH.
      CONCLUSIONS: D-CTH in elderly trauma patients taking antithrombotic agents shows
      no statistically significant or clinical benefit for diagnosing delayed
      intracranial hemorrhage after minor head injury. In those with delayed imaging
      showing new ICH, management was not significantly altered. Not enough data were
      available to predict which patients would develop D-ICH, even if asymptomatic.

PMID- 28439614
TI  - Internal Carotid Artery Stenosis and Collateral Recruitment in Stroke Patients.
AB  - PURPOSE: Leptomeningeal collaterals improve outcome in stroke patients. There is
      great individual variability in their extent. Internal carotid artery (ICA)
      stenosis may lead to more extensive recruitment of leptomeningeal collaterals.
      The purpose of this study was to evaluate the association of pre-existing ICA
      stenosis with leptomeningeal collateral filling visualized with computed
      tomography perfusion (CTP). METHODS: From a prospective acute ischemic stroke
      cohort, patients were included with an M1 middle cerebral artery (MCA) occlusion
      and absent ipsilateral, extracranial ICA occlusion. ICA stenosis was determined
      on admission CT angiography (CTA). Leptomeningeal collaterals were graded as good
      (>50%) or poor (<=50%) collateral filling in the affected MCA territory on CTP
      derived vessel images of the admission scan. The association between ipsilateral
      ICA stenosis >=70% and extent of collateral filling was analyzed using logistic
      regression. In a multivariable analysis the odds ratio (OR) of ICA stenosis >=70%
      was adjusted for complete circle of Willis, gender and age. RESULTS: We included
      188 patients in our analyses, 50 (26.6%) patients were classified as having poor
      collateral filling and 138 (73.4%) as good. Of the patients 4 with poor
      collateral filling had an ICA stenosis >=70% and 14 with good collateral filling.
      Unadjusted and adjusted ORs of ICA stenosis >=70% for good collateral filling
      were 1.30 (0.41-4.15) and 2.67 (0.81-8.77), respectively. Patients with poor
      collateral filling had a significantly worse outcome (90-day modified Rankin
      scale 3-6; 80% versus 52%, p = 0.001). CONCLUSION: No association was found
      between pre-existing ICA stenosis and extent of CTP derived collateral filling in
      patients with an M1 occlusion.

PMID- 28439616
TI  - [High intensity focused ultrasound (HIFU) : Importance in the treatment of
      prostate cancer].
AB  - BACKGROUND: High intensity focused ultrasound (HIFU) has been used since the
      beginning of the 1990s as an alternative treatment for prostate cancer.
      OBJECTIVE: Overview of the current status and critical review of the different
      indications for HIFU in the treatment of prostate cancer. MATERIAL AND METHODS:
      Review of the current literature on the indications, side effects, oncologic
      results and current guideline recommendations. RESULTS: The principle of HIFU is
      based on high energy sound waves, which lead to coagulation necrosis at the focal
      point. It can be applied for different indications: complete ablation of
      prostatic tissue is attempted in whole gland HIFU in the primary treatment of
      localized prostate cancer. There are several case series in the current
      literature with a maximum median follow-up of 8.1 years. The main side effect is
      the formation of bladder neck sclerosis. A further indication is for salvage HIFU
      in patients with localized recurrent prostate cancer after radiotherapy. This is
      a high-risk procedure due to increased risk of incontinence and formation of
      rectourethral fistula. Focal therapy is an innovative field aiming at partial
      prostate gland ablation with HIFU thereby reducing side effects. Technical
      improvements in HIFU enable treatment planning with fusion of multiparametric
      magnetic resonance imaging (mpMRI). Due to the experimental character, this
      should only be carried out within clinical trials. DISCUSSION: Due to a lack of
      prospective randomized trials and limited long-term results, whole gland HIFU is
      considered differently in the guidelines of European countries. Focal therapy is
      still experimental and should only be carried out within clinical trials.

PMID- 28439615
TI  - WIP1 phosphatase as pharmacological target in cancer therapy.
AB  - DNA damage response (DDR) pathway protects cells from genome instability and
      prevents cancer development. Tumor suppressor p53 is a key molecule that
      interconnects DDR, cell cycle checkpoints, and cell fate decisions in the
      presence of genotoxic stress. Inactivating mutations in TP53 and other genes
      implicated in DDR potentiate cancer development and also influence the
      sensitivity of cancer cells to treatment. Protein phosphatase 2C delta (referred
      to as WIP1) is a negative regulator of DDR and has been proposed as potential
      pharmaceutical target. Until recently, exploitation of WIP1 inhibition for
      suppression of cancer cell growth was compromised by the lack of selective small
      molecule inhibitors effective at cellular and organismal levels. Here, we review
      recent advances in development of WIP1 inhibitors and discuss their potential use
      in cancer treatment.

PMID- 28439617
TI  - [Stroke prophylaxis in atrial fibrillation : When, how and for whom?]
AB  - In patients suffering from atrial fibrillation (AF), modern antithrombotic
      therapy and anticoagulation strategies should be individualized based on shared
      decision making including patient preferences and the absolute and relative risks
      of stroke and bleeding. Estimation of the individual risk for stroke is still
      based on the CHA2DS2-VASc score. Based on the most recent guidelines for the
      management of AF, oral anticoagulation therapy should be considered for men with
      a CHA2DS2-VASc score >=1 and women with a score >=2, balancing the expected
      stroke reduction, risk of bleeding and patient preference. Both vitamin K
      antagonists and novel oral anticoagulants (NOAC) are effective for the prevention
      of stroke in AF. In AF patients treated with NOAC, kidney function should be
      regularly monitored to refine risk estimation and to enable dose adaptation. As
      an alternative to oral anticoagulation therapy, left atrial appendage occlusion
      may be considered for stroke prevention in patients with AF and contraindications
      for long-term anticoagulant treatment. This article provides a review of the
      indications and contraindications of modern stroke prophylaxis and discusses the
      approach to frequent clinical scenarios, such as treatment of patients with an
      acute coronary syndrome, coronary stent intervention or catheter ablation of AF.

PMID- 28439618
TI  - [Radiofrequency current or cryoballoon for ablation of atrial fibrillation? : Hot
      or cold?]
AB  - Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. The aim
      of therapy in symptomatic patients is the establishment of a stable sinus rhythm
      (SR). Catheter ablation with isolation of the pulmonary veins is the essential
      component of all forms of ablation therapy and provides the most effective
      treatment option. The most frequently used technologies for pulmonary vein
      isolation (PVI) are radiofrequency current (RFC)-based and cryoballoon (CB)
      guided ablation. Irrespective of the simplification of PVI, CB ablation is
      characterized by a short learning curve and short procedural times and
      demonstrated non-inferiority with respect to safety and efficacy when directly
      compared to RFC ablation for the treatment of patients with paroxysmal AF;
      however, the clinical outcome in patients with persistent AF is often
      insufficient when performing pulmonary vein isolation (PVI) alone for
      stabilization of SR. Differentiated RFC ablation is the treatment of choice when
      performing additional ablation strategies beyond PVI in order to improve clinical
      results with freedom from arrhythmia recurrence.

PMID- 28439620
TI  - Development of an optimal filter substrate for the identification of small
      microplastic particles in food by micro-Raman spectroscopy.
AB  - When analysing microplastics in food, due to toxicological reasons it is
      important to achieve clear identification of particles down to a size of at least
      1 MUm. One reliable, optical analytical technique allowing this is micro-Raman
      spectroscopy. After isolation of particles via filtration, analysis is typically
      performed directly on the filter surface. In order to obtain high qualitative
      Raman spectra, the material of the membrane filters should not show any
      interference in terms of background and Raman signals during spectrum
      acquisition. To facilitate the usage of automatic particle detection, membrane
      filters should also show specific optical properties. In this work, beside eight
      different, commercially available membrane filters, three newly designed metal
      coated polycarbonate membrane filters were tested to fulfil these requirements.
      We found that aluminium-coated polycarbonate membrane filters had ideal
      characteristics as a substrate for micro-Raman spectroscopy. Its spectrum shows
      no or minimal interference with particle spectra, depending on the laser
      wavelength. Furthermore, automatic particle detection can be applied when
      analysing the filter surface under dark-field illumination. With this new
      membrane filter, analytics free of interference of microplastics down to a size
      of 1 MUm becomes possible. Thus, an important size class of these contaminants
      can now be visualized and spectrally identified. Graphical abstract A newly
      developed aluminium coated polycarbonate membrane filter enables automatic
      particle detection and generation of high qualitative Raman spectra allowing
      identification of small microplastics.

PMID- 28439619
TI  - Association between bone mineral density, muscle strength, and vitamin D status
      in patients with myasthenia gravis: a cross-sectional study.
AB  - : Myasthenia gravis (MG) patients had low proximal hip BMD, which could be
      explained by reduced muscle strength, elevated bone resorption markers, vitamin D
      deficiency, and increased PTH levels in those with MG compared to controls.
      INTRODUCTION: Muscle strength is closely correlated with bone mineral density
      (BMD) and vitamin D status. Here, we evaluated muscle strength, BMD, and vitamin
      D status in a large sample of Chinese patients with MG. METHODS: In this cross
      sectional survey, 86 patients with MG without glucocorticoid treatment and 86
      healthy controls were included. Serum levels of 25-hydroxyvitamin D [25OHD],
      parathyroid hormone (PTH), bone turnover markers (BTMs), and BMD were measured
      and compared between the two groups. Grip strength and one-leg standing time
      (OLST) were also assessed in MG patients. RESULTS: Low grip strength and short
      OLST were found in 11 (12.8%) and 12 (14.0%) MG patients, respectively. There
      were 3 (3.5%) MG patients with low bone mass for chronological age. Serum beta C
      terminal telopeptide and PTH levels were higher (p < 0.001 and p = 0.001,
      respectively), and BMD at the femoral neck and trochanter were lower in MG
      patients (p < 0.001 and p < 0.001, respectively) compared to healthy controls. In
      patients with MG, grip strength was positively correlated with BMD. Serum 25OHD
      levels were lower in MG patients than in healthy controls (17.36 +/- 6.64 vs.
      22.11 +/- 7.28 ng/ml, p < 0.001). CONCLUSION: Grip strength was positively
      correlated with BMD in Chinese patients with MG. MG patients tended to have low
      proximal hip BMD, which may partially be explained by reduced muscle strength,
      vitamin D deficiency, increased PTH levels, and elevated bone resorption markers
      compared to controls.

PMID- 28439621
TI  - QTL mapping of domestication and diversifying selection related traits in round
      fruited semi-wild Xishuangbanna cucumber (Cucumis sativus L. var.
      xishuangbannanesis).
AB  - KEY MESSAGE: QTL analysis revealed 11 QTL underlying flowering time and fruit
      size variation in the semi-wild Xishuangbanna cucumber, of which, FT6.2 and FS5.2
      played the most important roles in determining photoperiod-dependent flowering
      time and round-fruit shape, respectively. Flowering time and fruit size are two
      important traits in domestication and diversifying selection in cucumber, but
      their genetic basis is not well understood. Here we reported QTL mapping results
      on flowering time and fruit size with F2 and F2:3 segregating populations derived
      from the cross between WI7200, a small fruited, early flowering primitive
      cultivated cucumber and WI7167, a round-fruited, later flowering semi-wild
      Xishuangbanna (XIS) cucumber. A linkage map with 267 microsatellite marker loci
      was developed with 138 F2 plants. Phenotypic data of male and female flowering
      time, fruit length and diameter and three other traits (mature fruit weight and
      number, and seedling hypocotyl length) were collected in multiple environments.
      Three flowering time QTL, FT1.1, FT5.1 and FT6.2 were identified, in which FT6.2
      played the most important role in conferring less photoperiod sensitive early
      flowering during domestication whereas FT1.1 seemed more influential in
      regulating flowering time within the cultivated cucumber. Eight consensus fruit
      size QTL distributed in 7 chromosomes were detected, each of which contributed to
      both longitudinal and radial growth in cucumber fruit development. Among them,
      FS5.2 on chromosome 5 exhibited the largest effect on the determination of round
      fruit shape that was characteristic of the WI7167 XIS cucumber. Possible roles of
      these flowering time and fruit size QTL in domestication of cucumber and crop
      evolution of the semi-wild XIS cucumber, as well as the genetic basis of round
      fruit shape in cucumber are discussed.

PMID- 28439622
TI  - Long-term impacts of parental migration on Chinese children's psychosocial well
      being: mitigating and exacerbating factors.
AB  - PURPOSE: Prolonged separation from migrant parents raises concerns for the well
      being of 60 million left behind children (LBC) in rural China. This study aimed
      to investigate the impact of current and previous parental migration on child
      psychosocial well-being, with a focus on emotional and behavioral outcomes, while
      considering factors in family care and support. METHODS: Children were recruited
      from schools in migrant-sending rural areas in Zhejiang and Guizhou provinces by
      random stratified sampling. A self-administered questionnaire measured children's
      psychosocial well-being, demographics, household characteristics, and social
      support. Multiple linear regression models examined the effects of parental
      migration and other factors on psychosocial difficulties. RESULTS: Data from 1930
      current, 907 previous, and 701 never LBC were included (mean age 12.4, SD 2.1).
      Adjusted models showed both previous and current parental migration was
      associated with significantly higher overall psychosocial difficulties, involving
      aspects of emotion, conduct, peer relationships, hyperactivity, and pro-social
      behaviors. Parental divorce and lack of available support demonstrated a strong
      association with greater total difficulties. While children in Guizhou had much
      worse psychosocial outcomes than those in Zhejiang, adjusted subgroup analysis
      showed similar magnitude of between-province disparities regardless of parental
      migration status. However, having divorced parents and lack of support were
      greater psychosocial risk factors for current and previous-LBC than for never
      LBC. CONCLUSIONS: Parental migration has an independent, long-lasting adverse
      effect on children. Psychosocial well-being of LBC depends more on the
      relationship bonds between nuclear family members and the availability of
      support, rather than socioeconomic status.

PMID- 28439623
TI  - Identification of multiple sources of the acidic charge variants in an IgG1
      monoclonal antibody.
AB  - Charge variants, especially acidic charge variants, of recombinant monoclonal
      antibodies are the major critical quality attributes in the biotechnology
      industry due to their potential influence on stability and biological activity.
      The chemical properties of the acidic charge variants have been challenging to
      fully characterize, and it is critical for process development and optimization.
      To completely understand the multiple sources of acidic charge variants, the
      major charge forms of an IgG1 monoclonal antibody were firstly isolated and then
      analyzed by a battery of characterization tools. It was found that various
      degrees of disulfide bond reduction, the deamination of HC-T8 Asn84 and HC-T35
      Asn388 and aggregation account for the majority of acidic charge heterogeneity
      and the terminal galactosylation content was in relation to the acidic charge
      heterogeneity. The correlation between acidic charge heterogeneity and
      galactosylation content was further explored by weak cation exchange
      chromatography with the use of beta1-4 galactosidase digestion. The results
      showed that galactosylation was not the source of the acidic charge variants per
      se. Meanwhile, to gain insights into the impact on binding affinity of monoclonal
      antibody to IgE and FcRn, charge variants were also analyzed by competitive ELISA
      and surface plasmon resonance, respectively. All isolated charge variants had
      similar affinity binding to IgE and FcRn binding relative to the starting
      material.

PMID- 28439624
TI  - Evidence for the formation of ScbR/ScbR2 heterodimers and identification of one
      of the regulatory targets in Streptomyces coelicolor.
AB  - The homologous transcriptional regulators ScbR and ScbR2 have previously been
      identified as gamma-butyrolactone (GBL) and antibiotic receptors, respectively.
      They regulate diverse physiological processes in Streptomyces coelicolor in
      response to GBL and antibiotic signals. In this study, ScbR and ScbR2 proteins
      were shown to interact using a bacterial two-hybrid system where adenylate
      cyclase activity was reconstituted in Escherichia coli BTH101. These ScbR/ScbR2
      interactions in S. coelicolor were then demonstrated by co-immunoprecipitation.
      The ScbR/ScbR2 heterodimer was shown to co-exist with their ScbR and ScbR2
      respective homodimers. When potential operator targets in S. coelicolor were
      investigated, the heterodimer was found to bind in the promoter region of
      sco5158, which however was not a target for ScbR or ScbR2 homodimers. These
      results revealed a new mechanism of regulation by ScbR and ScbR2 in S.
      coelicolor.

PMID- 28439625
TI  - "Direct MPR": A Useful Tool for Oblique CT Fluoroscopy-Assisted Puncture.
AB  - OBJECTIVE: Conventional multiplanar reconstruction (MPR) imaging can be used as a
      tool for planning oblique puncture procedures, but it takes a few minutes to
      reconstruct and is not appropriate for real-time CT fluoroscopy-assisted
      puncture. Recently, new MPR technology has been used that requires only 8 s and
      makes it possible to obtain a nearly real-time CT fluoroscopy-assisted oblique
      puncture. We refer to it as "direct MPR." This is the first clinical report of
      this technique. METHODS: Since February 2016, we have performed real-time, CT
      guided oblique punctures with this new technology, "direct MPR," using an angio
      CT system. We retrospectively reviewed all of our procedures with this new method
      between February 2016 and June 2016. RESULTS: We used this technique for 14 cases
      during the study period. Eight cases were radiofrequency ablation (RFA) for
      hepatocellular carcinoma (HCC), four were biopsies (lung and adrenal gland), and
      two were for percutaneous abscess drainage. Six of eight RFA cases were for HCC
      located immediately below the diaphragm. Both of the drainage cases were
      abscesses located immediately below the diaphragm. All procedures were
      successfully completed. The average length of the lesion in the RFA cases was
      15.4 +/- 3.2 mm. The average length of the lesions in all of the cases was 30.9
      +/- 31.9 mm. The average craniocaudal angle was 32.5 degrees  +/- 14.0 degrees .
      CONCLUSIONS: Direct MPR makes CT-guided oblique puncture for inaccessible
      targets, especially those located immediately below diaphragm, easier and safer.
      LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 28439626
TI  - Reliability and validity of the 12-item WHODAS 2.0 in patients with Kashin-Beck
      disease.
AB  - The purpose of this study was to check the reliability and validity of the 12
      item Chinese version of the World Health Organization Disability Assessment
      Schedule 2.0 (WHODAS 2.0) for the assessment of disability in patients with
      Kashin-Beck disease (KBD). We recruited 219 patients with KBD from the high-risk
      KBD area in the Shaanxi province, using stratified multistage random sampling. We
      assessed each patient using the Chinese version of the 12-item WHODAS 2.0 and the
      Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC).
      Statistical evaluations of the instruments consisted of Cronbach's alpha,
      intraclass correlation coefficient (ICC), confirmatory factor analysis (CFA), and
      Pearson's correlation coefficient. Cronbach's alpha and ICC for the six domains
      ranged from 0.704 to 0.906 and 0.690 to 0.852, respectively. A six-factor
      structure fits the data well (CFI = 0.967, TLI = 0.944, RMSEA = 0.08). Regarding
      convergent validity, the four domains of the 12-item WHODAS 2.0 (getting around,
      self-care, life activity, and participation) showed moderate-to-strong
      correlation for all three domains of the WOMAC (0.428 < |r| < 0.804). Regarding
      divergent validity, the two domains of the 12-item WHODAS 2.0 (understanding and
      communication, and getting along with people) showed weak correlation for the
      three domains of WOMAC (0.182 < |r| < 0.295). The Chinese version of 12-item
      WHODAS 2.0 questionnaire is a reliable and valid instrument when administered to
      KBD patients.

PMID- 28439627
TI  - Nigral injection of a proteasomal inhibitor, lactacystin, induces widespread
      glial cell activation and shows various phenotypes of Parkinson's disease in
      young and adult mouse.
AB  - Proteinaceous inclusions, called Lewy bodies, are used as a pathological hallmark
      for Parkinson's disease (PD). Lewy bodies contain insoluble alpha-synuclein
      (aSyn) and many other ubiquitinated proteins, suggesting a role for protein
      degradation system failure in the PD pathogenesis. Indeed, proteasomal
      dysfunction has been linked to PD but commonly used in vivo toxin models, such as
      6-OHDA or MPTP, do not have a significant effect on the proteasomal system or
      protein aggregation. Therefore, we wanted to study the characteristics of a
      proteasomal inhibitor, lactacystin, as a PD model on young and adult mice. To
      study this, we performed stereotactic microinjection of lactacystin above the
      substantia nigra pars compacta in young (2 month old) and adult (12-14 month old)
      C57Bl/6 mice. Motor behavior was measured by locomotor activity and cylinder
      tests, and the markers of neuroinflammation, aSyn, and dopaminergic system were
      assessed by immunohistochemistry and HPLC. We found that lactacystin induced a
      Parkinson's disease-like motor phenotype 5-7 days after injection in young and
      adult mice, and this was associated with widespread neuroinflammation based on
      glial cell markers, aSyn accumulation in substantia nigra, striatal dopamine
      decrease, and loss of dopaminergic cell bodies in the substantia nigra and
      terminals in the striatum. When comparing young and adult mice, adult mice were
      more sensitive for dopaminergic degeneration after lactacystin injection that
      further supports the use of adult mice instead of young when modeling
      neurodegeneration. Our data showed that lactacystin is useful in modeling various
      aspects of Parkinson's disease, and taken together, our findings emphasize the
      role of a protein degradation deficit in Parkinson's disease pathology, and
      support the use of proteasomal inhibitors as Parkinson's disease models.

PMID- 28439628
TI  - Visual salience of the stop-signal affects movement suppression process.
AB  - We investigated how the ability to suppress an impending movement is affected by
      the visual salience of the stop-signal in a reaching countermanding task. We
      found that when the stop-signal was easy to detect, stop performance was better
      than when the stop-signal was difficult to detect. In an exploratory analysis, we
      also found that the change in salience of the stop-signal can have an effect on
      the speed of response in trials following the stop-signal. This effect occurred
      together with strategic slowing down after an error in inhibiting was committed
      and together with a repetition priming effect due to the stop-signal presented in
      the previous trial. Our results suggest the need to investigate more in depth the
      afferent processing stage of the inhibitory control of movement and how task
      demands can affect its functioning.

PMID- 28439629
TI  - Transitioning to the direct anterior approach in total hip arthroplasty. Is it a
      true muscle sparing approach when performed by a low volume hip replacement
      surgeon?
AB  - PURPOSE: We conducted this study to establish if the transition from a lateral
      approach (LA) to the direct anterior approach (DAA) for a low volume hip
      arthroplasty surgeon during the steep learning curve can be performed maintaining
      the muscle sparing approach of the DAA without increasing the complication rates.
      METHODS: In this controlled, prospective, randomized clinical study we
      investigated 70 patients (35 DAA, 35 LA) with similar demographics that underwent
      a total hip arthroplasty. Assessment of the two approaches consisted of
      determining the invasiveness through serum markers for muscle damage (i.e.
      myoglobin, creatine kinase and lactate dehydrogenase), the operative parameters
      such as post-operative pain and rescue medication consumption, the component
      positioning and complication rates. RESULTS: Post-operative myoglobin levels were
      higher (p < 0.001) in the LA group (326.42 +/- 84.91 ng/mL) as compared to the
      DAA group (242.80 +/- 71.03 ng/mL), but with no differences regarding other
      biomarkers for muscle damage. Pain levels were overall lower in the DAA group,
      with a statistical and clinical difference during surgery day (p < 0.001)
      associated with lower (p < 0.001) rescue medication consumption (median 1 (1; 3)
      mg morphine vs. 3 (2; 4) mg morphine). Most patients in the LA group reported
      chronic post-operative pain throughout all three evaluated months, while the
      majority of patients in the DAA group reported no pain after week six. Component
      positioning did not differ significantly between groups and neither did
      complication rates. CONCLUSION: The DAA can be transitioned from the LA safely,
      without higher complication rates while maintaining its muscle spearing
      advantages when performed by a low volume hip arthroplasty surgeon.

PMID- 28439630
TI  - Myriocin treatment of CF lung infection and inflammation: complex analyses for
      enigmatic lipids.
AB  - Our aim was to use quantitative and qualitative analyses to gain further insight
      into the role of ceramide in cystic fibrosis (CF). Sphingolipid ceramide is a
      known inflammatory mediator, and its accumulation in inflamed lung has been
      reported in different types of emphysema, chronic obstructive pulmonary disease
      and CF. CF is caused by a mutation of the chloride channel and associated with
      hyperinflammation of the respiratory airways and high susceptibility to ongoing
      infections. We have previously demonstrated that de novo ceramide synthesis is
      enhanced in lung inflammation and sustains Pseudomonas aeruginosa pulmonary
      infection in a CF murine model. We used liquid chromatography and matrix-assisted
      laser desorption/ionization (MALDI) imaging coupled with mass spectrometry,
      confocal laser scan microscopy and histology analyses to reveal otherwise
      undecipherable information. We demonstrated that (i) upregulated ceramide
      synthesis in the alveoli is strictly related to alveolar infection and
      inflammation, (ii) alveolar ceramide (C16) can be specifically targeted by
      nanocarrier delivery of the ceramide synthesis inhibitor myriocin (Myr) and (iii)
      Myr is able to downmodulate pro-inflammatory lyso-PC, favouring an increase in
      anti-inflammatory PCs. We concluded that Myr modulates alveolar lipids milieu,
      reducing hyperinflammation and favouring anti-microbial effective response in CF
      mouse model.

PMID- 28439631
TI  - Polar localization of MreB actin is inhibited by anionic phospholipids in the rod
      shaped bacterium Escherichia coli.
AB  - Bacterial actin MreB is required for the maintenance of cell polarity. MreB is
      located underneath the cell membrane and mainly localizes at a central
      cylindrical part of the cell. In addition, it has recently been found that
      anionic phospholipids (aPLs: phosphatidylglycerol and cardiolipin) play a crucial
      role in excluding MreB from the cell poles. Subcellular localization of MreB is
      positively and negatively regulated by membrane curvature and aPLs, respectively.

PMID- 28439632
TI  - A rat hysteropexy model for evaluating adhesion formation and comparison of two
      different structured meshes.
AB  - INTRODUCTION AND HYPOTHESIS: Peritonization of mesh during sacrohysteropexy is
      generally advocated to prevent adhesions to the viscera; however, randomized
      clinical trials are lacking, and peritonization may not be completely possible in
      a laparoscopic hysteropexy procedure. Our main objective was to describe a basic
      experimental rat sacrohysteropexy model. We hypothesized that even when
      peritoneal closure was omitted, using composite mesh would result in less
      adhesions to the viscera. METHODS: Twenty in-bred female virgin Wistar Hannover
      rats were used in this study. Standardized hysteropexy procedure and adhesion
      model is described step by step with two different mesh materials: polypropylene
      and a composite polyester. Mesh was anchored between the posterior cervix and
      anterior longitudinal ligament of the lumbar vertebrae. Macroscopic adhesion
      scores and histopathological tissue reaction was investigated. RESULTS:
      Macroscopically, the surface area involved in adhesions was similar between
      groups. However, adhesions in the polypropylene group were more dense, required
      sharp dissection for lysis, and yielded higher total macroscopic adhesion scores
      (p < 0.001). Histologically, a more pronounced host inflammatory response was
      encountered in the polyester group (p < 0.001). CONCLUSIONS: We describe a rat
      hysteropexy model and a previously established uterine adhesion model. Adhesion
      scores in the composite mesh group were lower, and bowel involvement was not
      seen. Our findings are promising, and further research investigating antiadhesive
      composite mesh use for hysterosacropexy would be appropriate, especially when
      peritoneal closure is omitted.

PMID- 28439633
TI  - Cystodistension versus cystoscopy in patients with refractory detrusor
      overactivity: a randomized controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: Cystodistension may be offered as a treatment for
      patients with refractory overactive bladder. The reported efficacy is based on a
      number of case series. This study was designed to evaluate the efficacy of
      cystodistension in a randomized trial. METHODS: This was a randomized study
      comparing cystoscopy combined with cystodistension with cystoscopy alone. The
      primary outcome was improvement in the Urgency Perception Scale (UPS) score.
      Symptoms were assessed using the ICIQ Female Lower Urinary Tract Symptoms (ICIQ
      FLUTS). Quality of life was assessed using the Urinary Distress Inventory (UDI).
      RESULTS: A total of 77 patients were recruited into the study with 42 randomized
      into the cystodistension arm and 35 into the cystoscopy-only arm. UPS scores had
      improved in both the cystodistension (41%) and cystoscopy (44%) arms at 6 weeks,
      but cystodistension provided no added benefit over cystoscopy alone. There was a
      significant improvement in ICIQ-FLUTS scores in the cystoscopy-only arm at 6
      weeks (p = 0.01), but there was no significant improvement in the cystodistension
      arm (p = 0.09). At 6 weeks there were significant improvements in UDI scores in
      both arms (both p = 0.01). Despite statistical improvements at 6 weeks, no
      clinically therapeutic benefit was maintained by either procedure at 6 months.
      CONCLUSIONS: Cystoscopy produces some short-term improvement in bladder symptoms,
      but cystodistension does not.

PMID- 28439634
TI  - Long-term clinical outcomes with the retropubic tension-free vaginal tape (TVT)
      procedure compared to Burch colposuspension for correcting stress urinary
      incontinence (SUI).
AB  - INTRODUCTION AND HYPOTHESIS: The retropubic tension-free vaginal tape (TVT)
      procedure replaced Burch colposuspension as the primary surgical method for
      stress urinary incontinence (SUI) and mixed urinary incontinence (MUI) in women
      in our department in 1998. In this study we compared the short-term and long-term
      clinical outcomes of these surgical procedures. METHODS: Using a case series
      design, we compared the last 5 years of the Burch procedure (n = 127, 1994-1999)
      with the first 5 years of the retropubic TVT procedure (n = 180, 1998-2002).
      Information from the medical records was transferred to a case report form
      comprising data on perioperative and long-term complications as well as
      recurrence of UI, defined as bothersome UI or UI in need of repeat surgery. Other
      endpoints were rates of perioperative and late complications and the rates of
      prolapse surgery after primary surgery. The data were analyzed with the chi
      squared and t tests and survival analysis using SPSS. RESULTS: The cumulative
      recurrence rate of SUI in women with preoperative SUI was significantly higher
      after the Burch procedure, but no difference was observed in women with MUI.
      There were no significant differences in rates of perioperative and late
      complications. At 12 years there was a significant increase in rates of repeat
      surgery for incontinence and prolapse in women after the Burch procedure.
      CONCLUSIONS: The long-term efficacy of TVT surgery was superior to that of Burch
      colposuspension in women with SUI. In addition, the rate of late prolapse surgery
      was significantly higher after the Burch procedure.

PMID- 28439635
TI  - High incidence of partially anatomic tunnel placement in primary single-bundle
      ACL reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate tunnel position and width in
      failed primary single-bundle (SB) anterior cruciate ligament (ACL)
      reconstructions. It was hypothesized that both femoral and tibial bone tunnels
      are frequently malplaced in terms of a partially anatomic position in the setting
      of failed SB ACL reconstruction. METHODS: Patients with recurrent instability
      following isolated SB ACL reconstruction using hamstring tendon autografts,
      undergoing revision ACL surgery, were retrospectively included. Further inclusion
      criteria were age >18 years and availability of preoperative computed tomography
      (CT) scans and radiographs of the affected knee. Patients with multiligamentous
      instabilities as well as incomplete or poor radiographs were excluded. Tunnel
      position was evaluated according to the method described by Harner et al. and
      Staubli and Rauschning. Tunnel width was determined on CT scans perpendicular to
      the bone tunnel axis at three different heights of each bone tunnel. RESULTS:
      Eighty-two patients met the inclusion criteria and were considered for
      radiological analysis. Femoral tunnels were graded as anatomic in 60% (49 of 82)
      of all cases. In the remaining 40% (33/82), 27% of the tunnels were placed
      partially anatomic and 13% were graded as non-anatomic. Tibial tunnel placement
      was found to be anatomic in 54% (44/82) of all cases, partially anatomic in 45%
      and non-anatomic in 1% of the cases. No statistically significant difference
      between anatomic or partially anatomic tunnel position and tunnel diameter,
      neither for the femoral nor for the tibial side, was observed (n.s.). CONCLUSION:
      The present study demonstrates that there is a high incidence of partially
      anatomic placed tunnels in failed SB ACL reconstruction. Tunnel width was not
      associated with tunnel position. Clinically, partially anatomic bone tunnels
      frequently require a staged procedure with bone grafting and subsequent ACL
      revision surgery. Thus, surgeons should carefully analyse tunnel position and
      width preoperatively to properly plan ACL revision surgery.

PMID- 28439636
TI  - Kinematic alignment is a possible alternative to mechanical alignment in total
      knee arthroplasty.
AB  - PURPOSE: A systematic review was conducted to answer the following questions: (1)
      Does kinematically aligned (KA) total knee arthroplasty (TKA) achieve clinical
      outcomes comparable to those of mechanically aligned (MA) TKA? (2) How do the
      limb, knee, and component alignments differ between KA and MA TKA? (3) How is
      joint line orientation angle (JLOA) changed from the native knee in KA TKA
      compared to that in MA TKA? METHODS: Nine full-text articles in English that
      reported the clinical and radiological outcomes of KA TKA were included. Five
      studies had a control group of patients who underwent MA TKA. Data on patient
      demographics, clinical scores, and radiological results were extracted. There
      were two level I, one level II, three level III, and three level IV studies. Six
      of the nine studies used patient-specific instrumentation, one study used
      computer navigation, and two studies used manual instrumentation. RESULTS: The
      clinical outcomes of KA TKA were comparable or superior to those of MA TKA with a
      minimum 2-year follow-up. Limb and knee alignment in KA TKA was similar to those
      in MA TKA, and component alignment showed slightly more varus in the tibial
      component and slightly more valgus in the femoral component. The JLOA in KA TKA
      was relatively parallel to the floor compared to that in the native knee and not
      oblique (medial side up and lateral side down) compared to that in MA TKA. The
      implant survivorship and complication rate of the KA TKA were similar to those of
      the MA TKA. CONCLUSION: Similar or better clinical outcomes were produced by
      using a KA TKA at early-term follow-up and the component alignment differed from
      that of MA TKA. KA TKA seemed to restore function without catastrophic failure
      regardless of the alignment category up to midterm follow-up. The JLOA in KA TKA
      was relatively parallel to the floor similar to the native knee compared to that
      in MA TKA. The present review of nine published studies suggests that relatively
      new kinematic alignment is an acceptable and alternative alignment to mechanical
      alignment, which is better understood. Further validation of these findings
      requires more randomized clinical trials with longer follow-up. LEVEL OF
      EVIDENCE: Level II.

PMID- 28439637
TI  - Tibiofemoral rotational alignment affects flexion angles in navigated posterior
      stabilized total knee arthroplasty.
AB  - PURPOSE: To investigate the tibiofemoral rotational profiles during navigated
      posterior-stabilized (PS) total knee arthroplasty (TKA) and investigate the
      effect on post-operative maximum flexion angles. METHODS: Twenty-five subjects,
      treated with navigated PS TKA, were enrolled, and the effect of posterior
      cruciate ligament (PCL) resection and component implantation on tibiofemoral
      rotational kinematics was statistically evaluated. Then, the effect of rotational
      alignment changes on the post-operative maximum angles was retrospectively
      examined in 96 subjects using the multiple regression analysis. RESULTS: Tibial
      internal rotation was significantly increased in full extension (p < 0.01 and
      <0.001, respectively) and at 60 degrees  and 90 degrees  flexion (p < 0.05) after
      PCL resection, which further increased after implantation, compared with that
      before resection. The amount of tibial internal rotation from 90 degrees  flexion
      to maximum flexion was significantly decreased after PCL resection and
      implantation, compared with that before resection (p < 0.05). The internal
      changes in the rotational alignment were independent factors for the minimal
      improvement in the post-operative maximum flexion angles (R 2 = 0.078, p =
      0.0067). CONCLUSION: PCL resection changed the tibial rotational alignment and
      decreased the amount of tibial internal rotation. The implantation of PS
      components further increased the internal rotational alignment and could not
      compensate for the tibiofemoral rotation. Finally, the internal changes in
      rotational alignment affected the improvement of the maximum flexion angles,
      suggesting that rotational alignment is an important factor for improving post
      operative maximum flexion angles. LEVEL OF EVIDENCE: II.

PMID- 28439638
TI  - Total knee arthroplasty using ultra-congruent inserts can provide similar
      stability and function compared with cruciate-retaining total knee arthroplasty.
AB  - PURPOSE: Recently, ultra-congruent (UC) inserts have shown successful outcomes
      following total knee arthroplasty (TKA). It was hypothesized that patients in the
      UC group would not show significantly different in vivo stability or functional
      outcomes from those in the cruciate-retaining (CR) group. METHODS: The
      prospective study enrolled patients who had been treated with either CR or UC
      TKAs (38 cases in each group), after a minimum 3-year follow-up. The same
      surgical technique was used with the same femoral components in both groups
      except for the polyethylene inserts (CR or UC). The clinical outcome measures
      were knee range of motion (ROM), Hospital for Special Surgery (HSS) score, Knee
      Society (KS) score, and Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC) subscale score. The mediolateral laxity at full extension and
      anteroposterior laxity at 90 degrees  flexion were measured in stress radiographs
      and compared between the two groups. RESULTS: Both the CR and UC groups showed
      significant improvements in post-operative ROM, HSS, KS, and WOMAC scores without
      inter-group differences between two groups. Moreover, there were no differences
      in mediolateral or anteroposterior laxity between the two groups (p > 0.05).
      CONCLUSION: TKA with posterior cruciate ligament (PCL) resection using the UC
      design showed comparable functional outcomes with those of CR TKA and provided
      similar in vivo stability. Therefore, UC inserts can be a good option in TKA
      without bony box cut when the PCL is damaged during an operation. LEVEL OF
      EVIDENCE: II.

PMID- 28439640
TI  - The elusive role of B lymphocytes and islet autoantibodies in (human) type 1
      diabetes.
AB  - The role of B lymphocytes in the pathogenesis of type 1 diabetes in humans is not
      entirely evident. These cells are presumed to be important, but this assumption
      is largely based on animal models of autoimmune diabetes, where compelling
      evidence for the contribution of both B lymphocytes and insulin-specific
      autoantibodies to this disease is in place. For humans, this is much less the
      case; the exact way in which B lymphocytes and/or autoantibodies may contribute
      to type 1 diabetes is not yet known but the possibilities include a pathogenic
      function ('fire'), or they may represent a surrogate of loss of immune tolerance
      to beta cells ('smoke') or, indeed, they could be a marker of an attempt at
      immune regulation ('ice water'). In this issue of Diabetologia, a study by
      Willcox et al (DOI: 10.1007/s00125-017-4221-7 ) adds new information but no
      greater clarity on the relevance of B lymphocytes in type 1 diabetes, showing a
      decrease in germinal centre frequencies in donors with recent-onset type 1
      diabetes compared with control donors and donors with longstanding type 1
      diabetes. These new findings may guide the research community to design
      experiments to unambiguously define whether B lymphocytes or their products
      function as fire, smoke or perhaps ice water in the immunopathogenesis of type 1
      diabetes.

PMID- 28439639
TI  - Searching for consensus in the approach to patients with chronic lateral ankle
      instability: ask the expert.
AB  - PURPOSE: The purpose of this study is to propose recommendations for the
      treatment of patients with chronic lateral ankle instability (CAI) based on
      expert opinions. METHODS: A questionnaire was sent to 32 orthopaedic surgeons
      with clinical and scientific experience in the treatment of CAI. The questions
      were related to preoperative imaging, indications and timing of surgery,
      technical choices, and the influence of patient-related aspects. RESULTS: Thirty
      of the 32 invited surgeons (94%) responded. Consensus was found on several
      aspects of treatment. Preoperative MRI was routinely recommended. Surgery was
      considered in patients with functional ankle instability after 3-6 months of non
      surgical treatment. Ligament repair is still the treatment of choice in patients
      with mechanical instability; however, in patients with generalized laxity or poor
      ligament quality, lateral ligament reconstruction (with grafting) of both the
      ATFL and CFL should be considered. CONCLUSIONS: Most surgeons request an MRI
      during the preoperative planning. There is a trend towards earlier surgical
      treatment (after failure of non-surgical treatment) in patients with mechanical
      ligament laxity (compared with functional instability) and in high-level
      athletes. This study proposes an assessment and a treatment algorithm that may be
      used as a recommendation in the treatment of patients with CAI. LEVEL OF
      EVIDENCE: V.

PMID- 28439641
TI  - Data-driven metabolic subtypes predict future adverse events in individuals with
      type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Previously, we proposed that data-driven metabolic subtypes
      predict mortality in type 1 diabetes. Here, we analysed new clinical endpoints
      and revisited the subtypes after 7 years of additional follow-up. METHODS:
      Finnish individuals with type 1 diabetes (2059 men and 1924 women, insulin
      treatment before 35 years of age) were recruited by the national multicentre
      FinnDiane Study Group. The participants were assigned one of six metabolic
      subtypes according to a previously published self-organising map from 2008.
      Subtype-specific all-cause and cardiovascular mortality rates in the FinnDiane
      cohort were compared with registry data from the entire Finnish population. The
      rates of incident diabetic kidney disease and cardiovascular endpoints were
      estimated based on hospital records. RESULTS: The advanced kidney disease subtype
      was associated with the highest incidence of kidney disease progression (67.5%
      per decade, p < 0.001), ischaemic heart disease (26.4% per decade, p < 0.001) and
      all-cause mortality (41.5% per decade, p < 0.001). Across all subtypes, mortality
      rates were lower in women compared with men, but standardised mortality ratios
      (SMRs) were higher in women. SMRs were indistinguishable between the original
      study period (1994-2007) and the new period (2008-2014). The metabolic syndrome
      subtype predicted cardiovascular deaths (SMR 11.0 for men, SMR 23.4 for women, p
      < 0.001), and women with the high HDL-cholesterol subtype were also at high
      cardiovascular risk (SMR 16.3, p < 0.001). Men with the low-cholesterol or good
      glycaemic control subtype showed no excess mortality. CONCLUSIONS/INTERPRETATION:
      Data-driven multivariable metabolic subtypes predicted the divergence of
      complication burden across multiple clinical endpoints simultaneously. In
      particular, men with the metabolic syndrome and women with high HDL-cholesterol
      should be recognised as important subgroups in interventional studies and public
      health guidelines on type 1 diabetes.

PMID- 28439642
TI  - Have biomarkers failed in acute kidney injury? We are not sure.

PMID- 28439643
TI  - Have renal biomarkers failed in acute kidney injury? Yes.

PMID- 28439644
TI  - Have biomarkers failed in acute kidney injury? No.

PMID- 28439645
TI  - 'Permissive' hypercapnia in ARDS: is it passe?

PMID- 28439647
TI  - Prognostic Scoring System for Patients Who Present with a Gastric Outlet
      Obstruction Caused by Advanced Pancreatic Adenocarcinoma.
AB  - BACKGROUND: Gastroenterostomy and stent placement are the most common palliative
      procedures for patients with a gastric outlet obstruction caused by advanced
      pancreatic adenocarcinoma. Gastroenterostomy is regarded as the optimum treatment
      for patients in whom a longer survival is expected, while stent placement is
      preferred for patients whose survival is likely to be relatively short. However,
      prognosis of such patients has not been fully evaluated. METHODS: This study
      included patients undergoing gastroenterostomy or duodenal stent placement for
      gastric outlet obstruction caused by advanced pancreatic adenocarcinoma between
      2002 and 2015. Prognostic factors found to be significant based on a multivariate
      analysis were given a prognostic score according to their hazard ratios (HR). The
      overall survivals stratified according to the total prognostic score were
      compared. RESULTS: The median survival time of all cohorts was 4.2 months. The
      multivariate analyses demonstrated a neutrophil-to-lymphocyte ratio (NLR) >= 4
      (HR = 4.01, p < 0.001), presence of liver metastases (HR = 1.90, p = 0.002), and
      presence of cancer pain (HR = 2.08, p < 0.001) to be significant prognostic
      factors. Regarding the HR, NLR >= 4, liver metastases and cancer pain were
      subsequently scored as 2, 1, and 1, respectively. The median survival time was
      9.4 months in patients with a score of 0 or 1 and 3.3 months in patients with a
      score of 2-4, respectively. CONCLUSION: The scoring system clearly demonstrates
      the patient survival. Patients with scores of 0 or 1 are favorable candidates for
      gastroenterostomy, while patients with scores of 2-4 are candidates for stent
      placement.

PMID- 28439649
TI  - Differences in tibial subchondral bone structure evaluated using plain
      radiographs between knees with and without cartilage damage or bone marrow
      lesions - the Oulu Knee Osteoarthritis study.
AB  - OBJECTIVES: To investigate whether subchondral bone structure from plain
      radiographs is different between subjects with and without articular cartilage
      damage or bone marrow lesions (BMLs). METHODS: Radiography-based bone structure
      was assessed from 80 subjects with different stages of knee osteoarthritis using
      entropy of Laplacian-based image (ELap) and local binary patterns (ELBP),
      homogeneity index of local angles (HIAngles,mean), and horizontal (FDHor) and
      vertical fractal dimensions (FDVer). Medial tibial articular cartilage damage and
      BMLs were scored using the magnetic resonance imaging osteoarthritis knee score.
      Level of statistical significance was set to p < 0.05. RESULTS: Subjects with
      medial tibial cartilage damage had significantly higher FDVer and ELBP as well as
      lower ELap and HIAngles,mean in the medial tibial subchondral bone region than
      subjects without damage. FDHor, FDVer, and ELBP were significantly higher,
      whereas ELap and HIAngles,mean were lower in the medial trabecular bone region.
      Subjects with medial tibial BMLs had significantly higher FDVer and ELBP as well
      as lower ELap and HIAngles,mean in medial tibial subchondral bone. FDHor, FDVer,
      and ELBP were higher, whereas ELap and HIAngles,mean were lower in medial
      trabecular bone. CONCLUSIONS: Our results support the use of bone structural
      analysis from radiographs when examining subjects with osteoarthritis or at risk
      of having it. KEY POINTS: * Knee osteoarthritis causes changes in articular
      cartilage and subchondral bone * Magnetic resonance imaging is a comprehensive
      imaging modality for knee osteoarthritis * Radiography-based bone structure
      analysis can provide additional information of osteoarthritic subjects.

PMID- 28439648
TI  - Evaluation of 68Ga-DOTATOC PET/MRI for whole-body staging of neuroendocrine
      tumours in comparison with 68Ga-DOTATOC PET/CT.
AB  - OBJECTIVES: To compare the diagnostic performance of 68Ga-DOTATOC PET/MRI and
      68Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine
      tumours (NET). METHODS: Thirty patients with histopathologically confirmed NET
      underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI
      scans were prospectively evaluated with regard to lesion count, localization,
      nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and
      follow-up imaging served as the reference standards. The proportions of NET and
      non-NET lesions rated correctly were compared using McNemar's chi-squared test.
      The Wilcoxon test was used to assess differences in SUVmax and lesion
      conspicuity. The correlation between the SUVmax for the same lesions from each
      modality was analysed using Pearson's correlation coefficient (r). RESULTS:
      According to the reference standard, there were 197 lesions (142 NET, 55 non
      NET). Lesion-based analysis showed a higher proportion of correctly rated NET
      lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p = 0.031), whereas on PET/CT
      there was a higher proportion of correctly rated non-NET lesions (94.5% vs.
      83.6%, p = 0.031). SUVmax was strongly correlated (r = 0.86; p < 0.001) and did
      not differ significantly (p = 0.35) between the modalities. Overall conspicuity
      and NET lesion conspicuity were higher on PET/MRI (both p < 0.01). CONCLUSIONS:
      Ga-DOTATOC PET/MRI yielded a higher proportion of correctly rated NET lesions and
      should be regarded as a valuable alternative to 68Ga-DOTATOC PET/CT in whole-body
      staging of NET patients. KEY POINTS: * 68 Ga-DOTATOC PET/MRI correctly identified
      more NET lesions than 68 Ga-DOTATOC PET/CT. * 68 Ga-DOTATOC PET/MRI provides
      better NET lesion conspicuity than 68 Ga-DOTATOC PET/CT. * SUVmax values from the
      two modalities are strongly correlated and do not differ significantly.

PMID- 28439651
TI  - Contrast-enhanced T1 mapping-based extracellular volume fraction independently
      predicts clinical outcome in patients with non-ischemic dilated cardiomyopathy: a
      prospective cohort study.
AB  - OBJECTIVES: We aimed to evaluate the prognostic role of cardiac magnetic
      resonance imaging (CMR)-based extracellular volume fraction (ECV) in patients
      with non-ischemic dilated cardiomyopathy (NIDCM) and compare it with late
      gadolinium enhancement (LGE) parameters. METHODS: This was a single-center,
      prospective, cohort study of 117 NIDCM patients (71 men, 51.9 +/- 16.7 years) who
      underwent clinical 3.0-T CMR. Myocardial ECV and LGE were quantified on the left
      ventricular myocardium. The presence of midwall LGE was also detected. Nineteen
      healthy subjects served as controls. The primary end points were cardiovascular
      (CV) events defined by CV death, rehospitalization due to heart failure, and
      heart transplantation. RESULTS: During the follow-up period (median duration,
      11.2 months; 25th-75th percentile, 7.8-21.9 months), the primary end points
      occurred in 19 patients (16.2%). The ECV (per 3% and 1% increase) was associated
      with a hazard ratio of 1.80 and 1.22 (95% confidence interval [CI], 1.48-2.20 and
      1.14-1.30, respectively; p < 0.001) for the CV events. Multivariable analysis
      also indicated that ECV was an independent prognostic factor and had a higher
      prognostic value (Harrell's c statistic, 0.88) than LGE quantification values
      (0.77) or midwall LGE (0.80). CONCLUSION: CMR-based ECV independently predicts
      the clinical outcome in NIDCM patients. KEY POINTS: * T1-mapping-based ECV is a
      useful parameter of risk stratification in NIDCM * ECV has a higher prognostic
      value than LGE * Contrast-enhanced T1-mapping CMR is a feasible and safe method.

PMID- 28439650
TI  - Gadoxetic acid disodium-enhanced MR imaging of cholangiolocellular carcinoma of
      the liver: imaging characteristics and histopathological correlations.
AB  - OBJECTIVES: To review the gadoxetic acid disodium (EOB)-enhanced magnetic
      resonance (MR) imaging features of cholangiolocellular carcinoma (CoCC) of the
      liver and compare them with those of hepatocellular carcinoma (HCC) and
      intrahepatic cholangiocarcinoma (ICC). METHODS: EOB-enhanced MR images of 19
      patients with CoCC, 23 with ICC, and 51 with HCC were retrospectively evaluated
      qualitatively and quantitatively. Univariate and multivariate analyses were
      performed to determine the characteristic MR features of CoCC with
      histopathological-imaging correlation. RESULTS: Multivariate logistic regression
      analysis showed that dot-/band-shaped internal enhancement during the arterial
      and portal phases (P < 0.001), and larger arterial ring enhancement ratio (CoCC,
      0.13 +/- 0.04; ICC, 0.074 +/- 0.04; P = 0.013) were significantly independently
      associated with CoCC in contrast to ICC, whereas several MR features including
      progressive enhancement during the portal and late phases (P < 0.001), target
      appearance in the hepatocyte phase (P = 0.004), and vessel penetration (P =
      0.013) were significantly more frequently associated with CoCC than HCC. The dot
      /band-like internal enhancement (78.9% of CoCCs) histopathologically corresponded
      to the tumour cell nest with vascular proliferations and retained Glisson's
      sheath structure. CONCLUSIONS: EOB-enhanced MR features of CoCC largely differ
      from those of HCC but are similar to those of ICC. However, the finding of
      thicker arterial ring enhancement with dot-/band-like internal enhancement could
      help differentiate CoCC from ICC. KEY POINTS: * Gadoxetic acid-enhanced MR
      features of cholangiolocellular carcinoma (CoCC) resembled those of intrahepatic
      cholangiocarcinoma (ICC). * Gadoxetic acid-enhanced MR features of CoCC largely
      differed from those of hepatocellular carcinoma. * Dot-/band-like internal
      enhancement of CoCC may be helpful for differentiating from ICC. * Arterial ring
      enhancement of CoCC was larger than that of ICC.

PMID- 28439652
TI  - Myocardial extracellular volume fraction quantified by cardiovascular magnetic
      resonance is increased in hypertension and associated with left ventricular
      remodeling.
AB  - OBJECTIVES: To determine whether extracellular volume fraction (ECV)
      quantification by cardiac magnetic resonance (CMR) can demonstrate left ventricle
      (LV) abnormalities and relationship between ECV and LV remodeling in hypertension
      (HTN) patients METHODS: ECV quantification was prospectively performed in 134
      consecutive HTN patients and 97 healthy subjects. Individual and regional ECV
      were compared to the regions on late gadolinium enhancement (LGE) images.
      Statistical analysis of the relationship between LV global functional parameters
      and ECV was carried out using Pearson's correlation, Student's t test and
      multiple regressions. RESULTS: In the HTN group, 70.1% (94/134) were LGE negative
      and 29.9% (40/134) LGE positive. The mean ECV after adjusting for age, sex, BMI,
      diabetes, smoking and dyslipidaemia in healthy controls and LGE-negative patients
      were 26.9 +/- 2.67% and 28.5 +/- 2.9% (p < 0.001), respectively. The differences
      in ECV reached statistical significance among the regions of LGE, LGE-Peri, LGE
      remote and the normal area between the control and LGE-positive subgroup (all p <
      0.05). Global ECV significantly correlated with LVEF (r = -0.466, p < 0 .001) and
      LV hypertrophy (r = 0.667, p < 0.001). CONCLUSIONS: ECV can identify LV
      abnormalities at an early stage in HTN patients without LGE. These abnormalities
      may reflect an increase in diffuse myocardial fibrosis and are associated with LV
      remodeling. KEY POINTS: * Diffuse myocardial fibrosis may develop in hypertensive
      cardiomyopathy before conventional MRI detectable LGE. * ECV can identify
      myocardial fibrosis at an early stage in hypertensive patients. * Elevated ECV is
      associated with decreased LV global function and LV remodeling in hypertension.

PMID- 28439653
TI  - Malignancy estimation of Lung-RADS criteria for subsolid nodules on CT: accuracy
      of low and high risk spectrum when using NLST nodules.
AB  - PURPOSE: Lung-RADS proposes malignancy probabilities for categories 2 (<1%) and
      4B (>15%). The purpose of this study was to quantify and compare malignancy rates
      for Lung-RADS 2 and 4B subsolid nodules (SSNs) on a nodule base. METHODS: We
      identified all baseline SSNs eligible for Lung-RADS 2 and 4B in the National Lung
      Screening Trial (NLST) database. Solid cores and nodule locations were annotated
      using in-house software. Malignant SSNs were identified by an experienced
      radiologist using NLST information. Malignancy rates and percentages of
      persistence were calculated. RESULTS: Of the Lung-RADS 2SSNs, 94.3% (1790/1897)
      could be located on chest CTs. Likewise, 95.1% (331/348) of part-solid nodules
      >=6 mm in diameter could be located. Of these, 120 had a solid core >=8 mm,
      corresponding to category 4B. Category 2 SSNs showed a malignancy rate of 2.5%,
      exceeding slightly the proposed rate of <1%. Category 4B SSNs showed a malignancy
      rate of 23.9%. In both categories one third of benign lesions were transient.
      CONCLUSION: Malignancy probabilities for Lung-RADS 2 and 4B generally match
      malignancy rates in SSNs. An option to include also category 2 SSNs for upgrade
      to 4X designed for suspicious nodules might be useful in the future. Integration
      of short-term follow-up to confirm persistence would prevent unnecessary invasive
      work-up in 4B SSNs. KEY POINTS: * Malignancy probabilities for Lung-RADS 2/4B
      generally match malignancy risks in SSNs. * Transient rate between low-risk Lung
      RADS 2 and high-risk 4B lesions were similar. * Upgrade of highly suspicious Lung
      RADS 2 SSNs to Lung-RADS 4X might be useful. * Up to one third of the benign high
      risk Lung-RADS 4B lesions were transient. * Short-term follow-up confirming
      persistence would avoid unnecessary invasive work-up of 4B lesions.

PMID- 28439655
TI  - [Ocular graft versus host disease : Corneal complications].
AB  - BACKGROUND: Ocular graft-versus-host disease (GvHD) following allogeneic blood
      stem cell transplantation leads to immunologically induced alterations in many
      ocular tissues, particularly at the ocular surface. Within the framework of the
      main topic, this article focuses primarily on corneal complications in chronic
      ocular GvHD. OBJECTIVE: This article aims to promote understanding of the
      influencing factors, diagnostics, and therapeutic options pertaining to corneal
      complications in ocular GvHD. Furthermore, the possibilities for prevention are
      discussed. MATERIALS AND METHODS: This analysis is based on a literature review
      as well as on data from the Ophthalmology Clinic at the University Hospital
      Essen. RESULTS: Corneal complications often occur secondarily in ocular GvHD, as
      a consequence of severe inflammatory alterations of the conjunctiva or eyelid.
      Spontaneous corneal perforations associated with only mild symptoms are less
      common during the course of disease. From the ophthalmologist's perspective, it
      is important that the inflammatory activity of all the different ocular tissues
      is considered. Treatment may follow a stepwise scheme that includes substitution,
      immunosuppression, and surgical rehabilitation. CONCLUSION: Systematic diagnosis
      of ocular GvHD helps to prevent corneal complications or support early
      therapeutic intervention. An interdisciplinary approach to diagnosis and
      treatment planning is recommended, in order to optimize local and systemic
      immunosuppressive therapy.

PMID- 28439654
TI  - Imaging-based surrogate markers of transcriptome subclasses and signatures in
      hepatocellular carcinoma: preliminary results.
AB  - OBJECTIVES: In this preliminary study, we examined whether imaging-based
      phenotypes are associated with reported predictive gene signatures in
      hepatocellular carcinoma (HCC). METHODS: Thirty-eight patients (M/F 30/8, mean
      age 61 years) who underwent pre-operative CT or MR imaging before surgery as well
      as transcriptome profiling were included in this IRB-approved single-centre
      retrospective study. Eleven qualitative and four quantitative imaging traits
      (size, enhancement ratios, wash-out ratio, tumour-to-liver contrast ratios) were
      assessed by three observers and were correlated with 13 previously reported HCC
      gene signatures using logistic regression analysis. RESULTS: Thirty-nine HCC
      tumours (mean size 5.7 +/- 3.2 cm) were assessed. Significant positive
      associations were observed between certain imaging traits and gene signatures of
      aggressive HCC phenotype (G3-Boyault, Proliferation-Chiang profiles, CK19
      Villanueva, S1/S2-Hoshida) with odds ratios ranging from 4.44-12.73 (P <0.045).
      Infiltrative pattern at imaging was significantly associated with signatures of
      microvascular invasion and aggressive phenotype. Significant but weak
      associations were also observed between each enhancement ratio and tumour-to
      liver contrast ratios and certain gene expression profiles. CONCLUSIONS: This
      preliminary study demonstrates a correlation between phenotypic imaging traits
      with gene signatures of aggressive HCC, which warrants further prospective
      validation to establish imaging-based surrogate markers of molecular phenotypes
      in HCC. KEY POINTS: * There are associations between imaging and gene signatures
      of aggressive hepatocellular carcinoma. * Infiltrative type is associated with
      gene signatures of microvascular invasion and aggressiveness. * Infiltrative type
      may be a surrogate marker of microvascular invasion gene signature.

PMID- 28439656
TI  - [Management of paraophthalmic aneurysms : Review of endovascular treatment
      strategies].
AB  - BACKGROUND: Aneurysms of the cerebral vessels are relatively common and aneurysms
      of the ophthalmic segment of the internal carotid artery (ICA) represent
      approximately 10% of intradural aneurysms. ANATOMICAL ASPECTS: The ophthalmic
      segment of the ICA extends from the origin of the ophthalmic artery to the origin
      of the posterior communicating artery. Aneurysms can originate from the
      ophthalmic artery itself or directly from the ICA at a distance from the
      ophthalmic artery. The various anatomic configurations can alter the risks of
      treatment. SURGICAL TREATMENT: Surgical treatment of aneurysms of the ophthalmic
      segment poses unique challenges for the neurosurgeon, given the deep location and
      complex nearby structures and optic nerve. The necessity to remove the clinoid
      process can make the operation technically challenging. ENDOVASCULAR TREATMENT:
      Endovascular treatment of paraophthalmic aneurysms includes coil occlusion, and
      also stent- or balloon-assisted coil occlusion. More recently, hemodynamically
      active flow diverter stents improved the treatment results. CONCLUSION: The
      management of paraophthalmic aneurysms is associated with specific risks. Careful
      consideration of the available techniques is necessary before each invention.
      Coil-occlusion remains the first choice for ruptured paraophthalmic aneurysms.
      For unruptured paraophthalmic aneurysms flow diversion offers improved results.
      The overall complication rates of these procedures are low; however, cerebral
      ischemia, intracranial hemorrhage and visual complications must be considered in
      advance and the patient must be informed of the risks.

PMID- 28439658
TI  - Pan-Genomic Approaches in Lactobacillus reuteri as a Porcine Probiotic:
      Investigation of Host Adaptation and Antipathogenic Activity.
AB  - After the introduction of a ban on the use of antibiotic growth promoters (AGPs)
      for livestock, reuterin-producing Lactobacillus reuteri is getting attention as
      an alternative to AGPs. In this study, we investigated genetic features of L.
      reuteri associated with host specificity and antipathogenic effect. We isolated
      104 L. reuteri strains from porcine feces, and 16 strains, composed of eight
      strains exhibiting the higher antipathogenic effect (group HS) and eight strains
      exhibiting the lower effect (group LS), were selected for genomic comparison. We
      generated draft genomes of the 16 isolates and investigated their pan-genome
      together with the 26 National Center for Biotechnology Information-registered
      genomes. L. reuteri genomes organized six clades with multi-locus sequence
      analysis, and the clade IV includes the 16 isolates. First, we identified six L.
      reuteri clade IV-specific genes including three hypothetical protein-coding
      genes. The three annotated genes encode transposases and cell surface proteins,
      indicating that these genes are the result of adaptation to the host
      gastrointestinal epithelia and that these host-specific traits were acquired by
      horizontal gene transfer. We also identified differences between groups HS and LS
      in the pdu-cbi-cob-hem gene cluster, which is essential for reuterin and
      cobalamin synthesis, and six genes specific to group HS are revealed. While the
      strains of group HS possessed all genes of this cluster, LS strains have lost
      many genes of the cluster. This study provides a deeper understanding of the
      relationship between probiotic properties and genomic features of L. reuteri.

PMID- 28439659
TI  - Reported outcomes of children with newly diagnosed high-grade gliomas treated
      with nimotuzumab and irinotecan.
AB  - PURPOSE: The outcome of children with high-grade gliomas (HGGs) treated with
      radiation and adjuvant chemotherapy remains poor. The expression of epidermal
      growth factor receptor (EGFR) has been established in children with HGGs. This
      report demonstrated the outcomes of adjuvant nimotuzumab, an EGFR inhibitor, with
      irinotecan in pediatric HGGs. METHODS: Children with newly diagnosed HGGs were
      enrolled. Two weeks after surgery, nimotuzumab with a dose of 150 mg/m2 was given
      every week during radiation. After completion of radiation, a 4-week cycle of
      nimotuzumab (150 mg/m2) at week 1 and 3 and irinotecan (125 mg/m2) at week 1, 2,
      and 3 was given. RESULTS: Sixteen patients (5 females, 11 males), with a mean +/-
      SD age of 8.2 +/- 3.5 years were included. Tumors were located at the
      supratentorial region (50.0%), infratentorial region (43.8%), and both locations
      (6.2%). The 5-year PFS and OS were 19.9 +/- 11.6 and 31.5 +/- 13.0%,
      respectively. Median times of PFS and OS were 1.8 and 1.9 years, respectively.
      Prognostic factors related to good outcome were the location of tumor at the
      supratentorial region or outside brainstem and the extension of surgery. Side
      effects were minimal, with grade 1 anemia in three patients and diarrhea in one
      patient. Although, the adjuvant regimen of nimotuzumab and irinotecan slightly
      increases the overall outcome when compared to the historical study, the
      advantages of this protocol were minimal side effect, short period of
      hospitalization, and improved OS in patients who received extensive surgery.

PMID- 28439660
TI  - Catheter ablation of persistent atrial fibrillation : Long-term results of
      circumferential pulmonary vein ablation in combination with a linear lesion at
      the roof of the left atrium.
AB  - BACKGROUND: Catheter ablation has become the first line of therapy in patients
      with symptomatic, recurrent, drug-refractory atrial fibrillation. However,
      catheter ablation of persistent atrial fibrillation is still a challenge. Various
      relatively complex ablation strategies exist and their results are not very
      favorable. Therefore, the aim of our study was to evaluate a well-defined
      reasonable approach to catheter ablation of persistent atrial fibrillation. The
      strategy consisted of a circumferential pulmonary vein ablation in combination
      with a linear lesion at the roof of the left atrium. METHODS: A total of 150
      patients with symptomatic persistent atrial fibrillation were enrolled in this
      study. All patients underwent catheter ablation of persistent atrial fibrillation
      using the abovementioned approach. RESULTS: The ablation procedure could be
      performed as planned in all 150 patients. Five years after catheter ablation, the
      success rate was 71.3% (no arrhythmia recurrence in 107 out of 150 patients).
      There were no major complications during long-term follow-up. CONCLUSION:
      Catheter ablation of persistent atrial fibrillation can be performed safely and
      effectively using this ablation strategy providing favorable long-term follow-up
      results.

PMID- 28439661
TI  - Comparative study of p16 protein expression in squamous cell carcinomas from
      patients with epidermodysplasia verruciformis and patients without the disease.
AB  - Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with
      susceptibility to beta-human papilloma virus (HPV) infection. EV patients develop
      disseminated warts and non-melanoma skin cancer, mainly squamous cell carcinomas
      (SCC) that are locally aggressive. EV pathogenesis is not yet fully understood,
      but alterations in the p16 gene play a role in the pathogenesis of neoplasms
      caused by high-risk genital HPV. To explore its role in EV lesions, we compared
      p16 expression in SCC from patients with and without EV. Tissue microarray slides
      composed of 27 SCC from EV patients, and 35 from non-EV patients were stained
      with an anti-p16 antibody. Twenty (74%) EV tumors exhibited diffuse (nuclear and
      cytoplasmic) p16 expression, one (4%) displayed focal expression, and six (22%)
      displayed no p16 staining. Eleven (31%) SCC from non-EV patients presented
      diffuse p16 staining, 14 (40%) displayed focal expression and 10 (29%) did not
      express p16. The frequency of diffuse p16 expression was higher in EV tumors than
      in SCC from patients without EV. The frequency of diffuse p16 expression in
      moderately and poorly differentiated EV-SCC was similarly higher than non-EV
      tumors with the same degree of differentiation. The diffuse expression of p16 in
      EV-SCC suggests that changes in the p16 gene, probably resulting in a
      functionally defective protein, may be one factor determining the locally
      aggressive clinical behavior of SCC in young EV patients.

PMID- 28439662
TI  - The angular gyrus is a supramodal comparator area in action-outcome monitoring.
AB  - Predicting and processing the sensory consequences of one's own actions is
      essential to enable successful interactions with the environment. Previous
      studies have suggested that the angular gyrus detects discrepancies between
      predicted and actual action consequences, at least for unimodal feedback.
      However, most actions lead to multisensory consequences, raising the question
      whether previous models can sufficiently explain action-outcome processing. Here,
      we investigated neural comparator processes during detection of delays between
      action and unimodal or bimodal consequences in human subjects with fMRI, using
      parametric and connectivity analyses. Participants had to perform button presses,
      which led to the presentation of either a dot on the screen, a tone, or both,
      presented with a variable delay after the button press. Participants were asked
      to judge whether there was a delay between action and feedback. Activity in the
      angular gyrus correlated positively with delay for both visual, auditory, and
      audio-visual action consequences. Furthermore, the angular gyrus was functionally
      connected with midline structures such as the posterior cingulate cortex and
      precuneus in all conditions. Our results show that the angular gyrus is (1) a
      supramodal area, sensitive to delays in multiple modalities, and (2) functionally
      connected with self-referential areas during delay detection of both unimodal and
      bimodal action consequences. Overall, our results suggest that the angular gyrus
      functions as a mediator between perception and interpretation, and that this
      process is remarkably similar for unimodal and bimodal action consequences.

PMID- 28439663
TI  - Answer to the Letter to the Editor of C. Birkenmaier concerning "Rehydration of a
      degenerated disc on MRI synchronized with transition of Modic changes following
      stand-alone XLIF" by K. Kita, T. Sakai, M. Abe, Y. Takata and K. Sairyo (Eur
      Spine J; 2017). doi:10.1007/s00586-017-4945-6.

PMID- 28439664
TI  - Women at familial risk of breast cancer electing for prophylactic mastectomy:
      frequencies, procedures, and decision-making characteristics.
AB  - BACKGROUND: Some women of families at high risk of breast cancer (BC) choose
      prophylactic mastectomy (PM) in spite of ambiguous evidence for survival
      benefits. The aim of this study was to investigate counselees' characteristics,
      decisions on PM, and frequencies of different procedures to better understand how
      to tailor interventions. PATIENTS AND METHODS: Eight hundred and forty-nine
      counselees who attended interdisciplinary consultation for genetic risk
      adjustment at the University Hospital Heidelberg between July 2009 and July 2011
      received a tripartite questionnaire addressing sociodemographic characteristics,
      psychological parameters, behavioural questions, and medical data. RESULTS: Six
      hundred and twelve of the 849 counselees (72%) returned the questionnaire. Four
      hundred were classified as high risk of genetic BC (19.5% BRCA mutation carriers;
      4% unclassified variant (UV); and 76.5% calculated as high risk by pedigree). Two
      hundred and thirteen out of 400 (53%) were diagnosed with BC. Fourteen out of 54
      (27%) BRCA mutation carriers with BC chose contralateral PM (CPM) compared to
      24/126 (14%) without a mutation but with a personal BC history (p = 0.2175). Of
      those without BC, 12/27 (44%) mutation carriers opted for bilateral PM (BPM)
      compared to none without a mutation (p < 0.0001). Women who received any PM (CPM
      and BPM) reported a higher emotional burden from partners (p = 0.003) and family
      (p = 0.008), more worries regarding children and family (p = 0.003) and were
      associated with positive mutation status and higher heterozygous and lifetime
      risk (all p < 0.001). CONCLUSION: Although evidence on survival benefit is
      unclear in several clinical situations, a relevant number of counselees opt for
      PM. Counselees may decide based on other reasons than survival benefit.

PMID- 28439665
TI  - Maternal vitamin D status during pregnancy in Europe: the two sides of the story.

PMID- 28439666
TI  - Reply to Letter to the Editor to Maternal vitamin D status during pregnancy in
      Europe: the two sides of the story.

PMID- 28439667
TI  - Myricetin-induced brown adipose tissue activation prevents obesity and insulin
      resistance in db/db mice.
AB  - PURPOSE: Myricetin, a dietary flavonoid, is effective in the treatment of obesity
      and insulin resistance by increasing glucose transport and lipogenesis in
      adipocyte and diminishing systemic inflammation in obesity. However, it has not
      been revealed yet whether myricetin is associated with brown adipose tissue (BAT)
      activation that tightly mediates systemic energy metabolism. Therefore, this
      study assessed whether myricetin activated brown adipose tissue in db/db mouse.
      METHODS: Myricetin (400 mg/kg) in distilled water was fed daily by oral gavage to
      leptin receptor-deficient db/db male mice at 4 weeks of age for 14 weeks. Body
      weight change, glucose intolerance test, blood lipid profile and BAT activation
      using PET-CT were assessed. RESULTS: After myricetin treatment for 14 weeks,
      systemic insulin resistance and hepatic steatosis were significantly improved in
      db/db mice with body weight reduction and myricetin led to decreased adipocity,
      improved plasma lipid profiles and increased energy expenditure. Myricetin
      activated BAT by upregulating thermogenic protein expression and activating
      mitochondrial biogenesis, eventually increasing heat dissipation in skin after
      cold exposure. In iWAT, myricetin induced beige formation, increased thermogenic
      protein expression and activated mitochondrial biogenesis. Consistently,
      thermogenic gene expression was upregulated when myricetin was introduced in
      C3H10T1/2 cells during brown adipocytes differentiation. Moreover, the expression
      level of adiponectin was significantly increased in C3H10T1/2 cells, adipose
      tissues and plasma after myricetin treatment. CONCLUSIONS: These results
      highlight that myricetin prevents obesity and systemic insulin resistance by
      activating BAT and increasing adiponectin expression in BAT.

PMID- 28439668
TI  - Urinary podocalyxin as a possible novel marker of intrauterine nephrogenesis and
      extrauterine podocyte injury.
AB  - BACKGROUND: The number of nephrons at birth is determined during fetal
      development and is modulated thereafter by postnatal podocyte injury.
      Hyperfiltration, caused by a reduced number of nephrons, is a risk factor for
      chronic kidney disease. It is therefore important to monitor the formation of
      nephrons. METHODS: Urine samples were collected from infants within 1-2 days of
      birth, with follow-up sampling for preterm infants at 37-39 weeks of corrected
      age. Urinary levels of podocalyxin (PCX), beta2-microglobulin (beta2MG), N-acetyl
      beta-D-glucosaminidase (NAG), total protein (TP), microalbumin (mAlb) and
      creatinine were measured and the relationship between these markers evaluated.
      RESULTS: Seventy-nine neonates were enrolled in this study. Urinary levels of PCX
      at birth were higher than normal adult reference values, with levels increasing
      up to a gestational age of 36 weeks (p = 0.0242). At 37-39 weeks corrected age,
      urinary levels of PCX decreased to adult levels. The levels of PCX in the urine
      at birth were not correlated to urinary levels of beta2MG, NAG, TP and mAlb.
      CONCLUSIONS: An increased urinary level of PCX may be a marker of both active
      nephron formation and podocyte injury sustained at birth. As such, changes in
      urinary levels of PCX are likely to reflect adaptation of renal function to the
      extra-uterine environment.

PMID- 28439669
TI  - Effects of desiccation and starvation on thermal tolerance and the heat-shock
      response in forest ants.
AB  - Temperature increases associated with global climate change are likely to be
      accompanied by additional environmental stressors such as desiccation and food
      limitation, which may alter how temperature impacts organismal performance. To
      investigate how interactions between stressors influence thermal tolerance in the
      common forest ant, Aphaenogaster picea, we compared the thermal resistance of
      workers to heat shock with and without pre-exposure to desiccation or starvation
      stress. Knockdown (KD) time at 40.5  degrees C of desiccated ants was reduced 6%
      compared to controls, although longer exposure to desiccation did not further
      reduce thermal tolerance. Starvation, in contrast, had an increasingly severe
      effect on thermal tolerance: at 21 days, average KD time of starved ants was
      reduced by 65% compared to controls. To test whether reduction in thermal
      tolerance results from impairment of the heat-shock response, we measured basal
      gene expression and transcriptional induction of two heat-shock proteins (hsp70
      and hsp40) in treated and control ants. We found no evidence that either stressor
      impaired the Hsp response: both desiccation and starvation slightly increased
      basal Hsp expression under severe stress conditions and did not affect the
      magnitude of induction under heat shock. These results suggest that the co
      occurrence of multiple environmental stressors predicted by climate change models
      may make populations more vulnerable to future warming than is suggested by the
      results of single-factor heating experiments.

PMID- 28439671
TI  - Tobacco etch virus protease mediating cleavage of the cellulose-binding module
      tagged colored proteins immobilized on the regenerated amorphous cellulose.
AB  - In this study, four fusion proteins were designed, in which the N-terminal
      cellulose-binding module as the affinity tag was immobilized on the regenerated
      amorphous cellulose (RAC), and the release of the C-terminal colored proteins was
      detected easily and rapidly after on-resin cleavage using the free tobacco etch
      virus protease (TEVp) variant, or the immobilized cognate protease with a binding
      capacity of up to 220 mg protein per gram of RAC. The enhanced stability and
      repetitive use of the immobilized TEVp compensated slight loss of the catalytic
      efficiency toward the soluble protein substrate. On-resin cleavage and purity of
      the released target proteins are related to the context of the fusion tag, the
      incorporated linker composition, and the colored protein. Owing to low cost and
      high binding capacity of the RAC, the TEVp immobilized on the resin is an ideal
      alternative for removing fusion tag. The colored proteins are easily monitored in
      the on-resin process of fusion proteins, and rapid separation from RAC.

PMID- 28439670
TI  - Residual Recurrent Nerve Paralysis After Esophagectomy is Associated with
      Preoperative Lower Serum Albumin.
AB  - Esophagectomy for esophageal cancer is invasive thoracic surgery with a high
      incidence rate of postoperative complications and prolongation of
      hospitalization, even if the standardized clinical pathway improves the outcome
      (mortality and morbidity). Postoperative recurrent nerve paralysis (RNP) is
      related to respiratory complications concomitant with prolonged hospitalization.
      However, it has not been elucidated which factors affect the incidence and
      recovery of RNP. To detect the predictive factor for postoperative RNP, we
      focused on preoperative serum albumin. Patients who had esophageal cancer with
      standard esophagectomy were evaluated. In total, 94 patients were divided into
      three groups depending on the presence of RNP (46 in patients without RNP, 29 in
      those with transient RNP who recovered within 6 months follow-up and 19 in those
      with residual RNP). We retrospectively investigated factors associated with
      residual RNP. Preoperative lower serum albumin was associated with residual RNP.
      In addition, days to the resumption of oral intake and duration of stay in the
      hospita postoperatively were delayed in the group of residual RNP. Multiple
      regression analysis indicated that preoperative serum albumin was a predictive
      factor for residual RNP. Preoperative lower serum albumin level might be linked
      to residual RNP which could prolong the resumption of postoperative oral intake
      and shorten the period of stay at the hospital after esophagectomy, leading to
      unfavorable outcomes for patients.

PMID- 28439672
TI  - Altered intra- and interregional synchronization in the absence of the corpus
      callosum: a resting-state fMRI study.
AB  - Agenesis of the corpus callosum (AgCC) can result in subtle to severe cognitive
      deficits. Individuals with impaired cognition often show abnormalities on resting
      state functional magnetic resonance imaging (rs-fMRI). This study used rs-fMRI to
      investigate changes in regional homogeneity (ReHo) and functional connectivity
      (FC) among individuals with AgCC. AgCC individuals (n = 10) and age-, sex-, and
      education-matched healthy control subjects (n = 19) were included in this study.
      The ReHo values were calculated to represent spontaneous brain activity. The
      regions which showed altered ReHo were selected as seeds to compare FC with the
      whole brain between the AgCC group and the healthy control group. Compared with
      healthy control subjects, the AgCC individuals had increased ReHo in the left
      anterior cingulate gyrus, left rolandic operculum, and right precuneus and
      decreased ReHo in the right calcarine, right cingual gyrus and right cuneus
      gyrus. The right calcarine and the right lingual gyrus in the AgCC exhibited
      decreased FC with bilateral cuneus, superior occipital gyrus, Rolandic operculum,
      superior temporal gyrus, posterior central gyrus, and midcingulate gyrus.The
      right cuneus gyrus in the AgCC individuals exhibited decreased FC with the
      bilateral calcarine gyrus, left cuneus, and left superior occipital gyrus. Our
      study revealed several subareas within the visual cortex exhibited remarkable
      abnormalities of spontaneous brain activity and decreased FC with the higher
      order cognitive cortex.The abnormalities of ReHo and FC in AgCC individuals may
      provide new insights into the neurological pathophysiology.

PMID- 28439673
TI  - Duodenal adenocarcinoma successfully diagnosed with transabdominal
      ultrasonography.
AB  - Adenocarcinoma arising from the duodenum is relatively rare. Diagnosis of this
      disease at an early stage is difficult because its symptoms are usually
      nonspecific. We herein present a case in which duodenal adenocarcinoma was
      successfully found by transabdominal ultrasonography. Under ultrasonography, the
      tumor was located in the proximal duodenum apart from the papilla of Vater, and
      the serosa was intact. Other diagnostic modalities showed no evidence of adjacent
      organ invasion or distant metastasis. Therefore, pancreatoduodenectomy was
      performed and the postoperative course was uneventful. The ultrasonographic
      findings corresponded well with the pathological diagnosis. The following three
      procedures were essential in this case: systematic scanning of the digestive
      tract to determine the location of the lesion, graded compression ultrasound to
      remove air bubbles from the region of interest, and precise observation of the
      intestinal walls using proper transducers. The precise and skillful performance
      of transabdominal ultrasonography using a suitable device can help to diagnose
      duodenal adenocarcinoma, a rare malignancy.

PMID- 28439674
TI  - Adipose-derived stem cell (ASC)-enriched fat grafting: experiments using White
      rabbits and an automated cell processing apparatus.
AB  - The grafting of fat mixed with adipose-derived stem cells (ASCs) is being
      increasingly applied to compensate for the disadvantages of previous fat grafting
      methods. Devices that automatically isolate fat stem cells also have recently
      been developed. ASCs were isolated from the inguinal region of White rabbits
      using Icellator(r), and the number of cells and their viability were measured.
      The cell count per fat graft (mL) was adjusted to the following concentrations
      and subcutaneously transplanted into the back: Control group, Fat + PBS; Fat +
      ASCs (*0.5) group, 1.6 * 105 cells/mL; and Fat + ASCs (*1) group, 3.2 * 105
      cells/mL. Grafted fat weight was measured after 8 weeks, and histological,
      immunohistological, and specifically stained sections were prepared. Fat
      absorption was reduced in Fat + ASCs (*0.5) and Fat + ASCs (*1) groups. The
      number of blood vessels was higher in Fat + ASCs (*1) than in the control group,
      and blood vessel areas were higher in Fat + ASCs (*0.5) and Fat + ASCs (*1)
      groups than in the control group. The usefulness of the automated cell processing
      apparatus, Icellator(r), was confirmed, and the results obtained suggest that
      grafted ASCs promote the vascularization and engraftment of fat grafts.

PMID- 28439675
TI  - A pilot study assessing the efficacy of posterior tibial nerve stimulation in the
      treatment of low anterior resection syndrome.
AB  - BACKGROUND: Low anterior resection for rectal cancer often results in severe
      bowel dysfunction, specifically low anterior resection syndrome (LARS), with
      symptoms such as incontinence, urgency, and frequent bowel movements.
      Percutaneous tibial nerve stimulation (PTNS) resulted in a high rate of success
      in patients with fecal incontinence. The aim of this study was to evaluate the
      effectiveness of treatment with PTNS in LARS and to identify predictors of the
      outcome of the technique. METHODS: The study was conducted from May 2012 to April
      2015 at the Alvaro Cunqueiro Hospital, University Hospital Complex of Vigo,
      Spain. Ten patients with LARS were recruited consecutively. All patients
      underwent 2 sessions per week (30 min each one) for 6 weeks. Patients were
      followed for 3 weeks, and those who had a significant clinical improvement were
      recruited to a second phase of PTNS. Some patients presenting with relapse during
      follow-up underwent an additional phase of PTNS. Outcome measures included Wexner
      scores, quality of life scores, and urgency of defecation. RESULTS: Three
      patients did not complete the treatment due to poor response in the first phase.
      Incontinence was reduced in the remaining seven of ten patients. The median
      Wexner score at initial patient evaluation was 14 (IQR 10.75-18.5), which
      decreased to 10 (IQR 6.5-18) after treatment (p = 0.034). A statistically
      significant improvement was demonstrated in quality of life scale, lifestyle,
      depression, and daily defecation urgency (p < 0.05). LARS Score improvement was
      observed in five patients (50%) with a total resolution of LARS in 2 (20%).
      CONCLUSIONS: PTNS is an ambulatory treatment that could play an important role in
      the context of a multimodal treatment approach in patients with LARS. It could be
      a first-line treatment to identify non-responders to conservative management who
      need different and more invasive treatments.

PMID- 28439676
TI  - Post-recurrence chemotherapy for mesothelioma patients undergoing extrapleural
      pneumonectomy.
AB  - BACKGROUND: Additional chemotherapy is often not feasible in patients with
      recurrent malignant pleural mesothelioma (MPM) undergoing extrapleural
      pneumonectomy (EPP), due to deteriorated cardiopulmonary reserve. We thus
      examined the feasibility and efficacy of additional chemotherapy in patients with
      recurrent MPM after EPP. METHODS: A retrospective review was conducted of 59
      consecutive patients who underwent bi-/tri-modal treatment with induction
      chemotherapy, EPP, and radiation therapy from July 2004 to August 2013 at Hyogo
      College of Medicine (Nishinomiya, Japan). RESULTS: Of 59 patients, 39
      (male/female = 31/8, right/left = 15/24, pathological stage I/II/III/IV =
      1/7/23/3, bi-/tri-modality = 27/12) relapsed at a median age of 62 (range 37-71)
      years. The median time to recurrence after EPP was 11.6 months. Of the 39
      relapsed patients, 12 received best supportive care alone, six started but
      discontinued chemotherapy, and the remaining 21 (53%) completed more than three
      cycles of intravenous chemotherapy. The median survival time after EPP was
      significantly longer in 21 patients who received additional chemotherapy than in
      18 patients who did not (39.2 vs. 12.2 months, P = 0.009). CONCLUSIONS:
      Additional systemic chemotherapy was successfully administered in more than 50%
      of relapsed patients after bi-/tri-modal treatment, which included EPP, and
      resulted in a longer survival in comparison with best supportive care alone.

PMID- 28439677
TI  - AP-2alpha reverses vincristine-induced multidrug resistance of SGC7901 gastric
      cancer cells by inhibiting the Notch pathway.
AB  - Multidrug resistance (MDR) remains a major clinical obstacle in the treatment of
      gastric cancer (GC) since it causes tumor recurrence and metastasis. The
      transcription factor activator protein-2alpha (AP-2alpha) has been implicated in
      drug-resistance in breast cancer; however, its effects on MDR of gastric cancer
      are far from understood. In this study, we aimed to explore the effects of AP
      2alpha on the MDR in gastric cancer cells selected by vincristine (VCR).
      Decreased AP-2alpha levels were markedly detected by RT-PCR and Western blot in
      gastric cancer cell lines (BGC-823, SGC-7901, AGS, MKN-45) compared with that in
      the gastric epithelial cell line (GES-1). Furthermore, we found that the
      expression of AP-2alpha in SGC7901/VCR or SGC7901/adriamycin (ADR) cells was
      lower than in SGC7901 cells. Thus, a vector overexpressing AP-2alpha was
      constructed and used to perform AP-2alpha gain-of-function studies in SGC7901/VCR
      cells. The decreased IC50 values of the anti-cancer drugs in sensitive and
      resistant cells after transfect with pcDNA3.1/AP-2alpha were determined in
      SGC7901/VCR cells by MTT assay. Moreover, flow cytometry analysis indicated that
      overexpressed AP-2alpha induced cell cycle arrest in the G0/G1 phase and promoted
      cell apoptosis of VCR-selected SGC7901/VCR cells. RT-PCR and Western blot
      demonstrated that overexpressed AP-2alpha can significantly induce the down
      regulation of Notch1, Hes-1, P-gp and MRP1 in SGC7901/VCR cells. Similar effects
      can be observed when Numb (Notch inhibitor) was introduced. In addition, the
      intracellular ADR accumulation was markedly detected in AP-2alpha overexpressed
      or Numb cells. In conclusion, our results indicate that AP-2alpha can reverse the
      MDR of gastric cancer cells, which may be realized by inhibiting the Notch
      signaling pathway.

PMID- 28439678
TI  - Aquimarina seongsanensis sp. nov., isolated from sea water.
AB  - An orange, rod-shaped, gliding bacterium, designated strain CBA3208T, was
      isolated from sea water of Jeju Island, Republic of Korea. Cells were observed to
      be Gram-stain negative, strictly aerobic, catalase positive and oxidase negative
      and to hydrolyse starch, gelatin, and Tweens 40 and 80. The major fatty acids
      were identified as iso-C15:0, iso-C17:0 3-OH, and iso-C15:1 G. The only
      isoprenoid quinone was found to be menaquinone-6 (MK-6) and the major polar
      lipids were identified as phosphatidylethanolamine, two aminolipids and four
      unidentified polar lipids. The DNA G+C content of strain CBA3208T was determined
      to be 34.9 mol%. Strain CBA3208T is considered to represent a novel species of
      the genus Aquimarina, for which the name Aquimarina seongsanensis sp. nov. is
      proposed based on this polyphasic taxonomic analysis. The type strain is CBA3208T
      (=KACC 17667T =JCM 19529T).

PMID- 28439679
TI  - Screening lactic acid bacteria strains with ability to bind di-n-butyl phthalate
      via Turbiscan technique.
AB  - Di-n-butyl phthalate (DBP) is a ubiquitous environmental contaminant that poses a
      risk to humans. Previous work indicates that the ability of lactic acid bacteria
      (LAB) to bind phthalic acid esters is strain-specific. As cell suspensions of LAB
      strains in aqueous solution are likely to be colloidal dispersions, this study
      provided a technique to efficiently screen LAB strains that bind DBP via
      Turbiscan, which has been widely used to measure the stability of emulsions or
      colloidal dispersions. Eleven LAB strains belonging to Lactobacillus plantarum,
      Lb. pentosus, Lb. paralimentarius, Lb. helveticus, Leuconostoc mesenteroides, Lb.
      acidophilus, Bifidobacterium lactis, and Bifidobacterium bifidum species were
      used in this study, and seven of them were selected to test in an earlier stage
      of exploring the process for finding a screening method; others were used for a
      validation test. It was observed that the various values of the 10 h Turbiscan
      Stability Index (TSI) of the cell suspension from each strain, at the equilibrium
      time of dispersed particles according to the peak thickness of cell-suspensions
      as measured by Turbiscan, had significant negative correlations with the DBP
      binding percentage of LAB strains. Higher TSI values are correlated with lower
      binding of bacteria strains to DBP with a correlation coefficient of 0.8292. Cell
      surface hydrocarbons of LAB strains and their adherence were observed to
      correlate with DBP-binding percentages and may lead to the different states of
      aggregation or equilibrium of bacterial cell-suspensions, and the aggregation of
      bacterial cells resulted in fewer binding sites in the cell wall for DBP.
      Finally, four LAB strains were randomly selected to verify the feasibility of the
      method. In all, the findings demonstrate that TSI might be used as a tool to
      quickly screen strains that bind DBP. The present work could be extended to the
      removal of other toxic compounds, when screening of high-efficiency strains is
      required.

PMID- 28439680
TI  - Microbiological evaluation of infected pelvic lymphocele after robotic
      prostatectomy: potential predictors for culture positivity and selection of the
      best empirical antimicrobial therapy.
AB  - OBJECTIVES: To examine symptomatology and microbiology of infected lymphocele
      (LC) post-robotic-assisted radical prostatectomy and pelvic lymph node dissection
      (PLND) and to assess for potential predictors for LC fluid culture positivity.
      Secondly, to provide general recommendations about use of select antimicrobial
      therapy. METHODS: This was a single-center, IRB-approved, retrospective, case
      series review conducted between October 2008 and October 2014. Data included
      symptomatology, microbiology of symptomatic LC in men post-robotic prostatectomy
      and PLND. Those with infected LC were compared to those men with symptomatic LC
      in the absence of infection. RESULTS: Symptomatic LC was seen in 7% of men, and
      among those, infected LC was seen in 42%. Infected LC cultures showed
      predominance of G+ cocci such as S. aureus, coagulase-negative Staphylococcus
      species, S. pyogenes, S. fecalis and S. viridans. Monomicrobial infection was
      seen in 85%. Multivariate logistic regression showed leukocytosis [Odds: 12.3, p
      = 0.03, 95% CI (1.2-125)] was significant predictor for culture positivity,
      whereas trend toward significance for factors such CT findings of thickened walls
      around the LC +/- air. CONCLUSIONS: LC infection following PLND for prostate
      cancer is usually monomicrobial and caused by Gram+ cocci. GI tract and skin
      flora are the main habitat. High index of suspicion of infected LC is undertaken
      in the presence of leukocytosis, fever and abnormal CT findings. Based upon our
      local hospital antibiogram, combination of IV ampicillin/sulbactam and vancomycin
      is suggested as the best initial empiric therapy in treating these patients.

PMID- 28439681
TI  - Side-effects of pesticides used in irrigated rice areas on Telenomus podisi
      Ashmead (Hymenoptera: Platygastridae).
AB  - Telenomus podisi Ashmead (Hymenoptera: Platygastridae) is an important agent for
      the biological control of stink bug eggs in irrigated rice areas and the best
      strategy for its preservation is the use of selective pesticides. The aim of this
      study was to know the side-effects of pesticides used in Brazilian irrigated rice
      areas on egg parasitoid T. podisi. We evaluated, under laboratory conditions, 13
      insecticides, 11 fungicides, 11 herbicides, and a control (distilled water) in
      choice and no-choice tests. In the no-choice tests, the pesticides were sprayed
      at pre and post-parasitism stages (egg and larval stages of T. podisi). In the
      choice tests, sprays were conducted only at pre-parasitism stages. For all tests,
      we prepared cards with 25 eggs of the alternative host Euschistus heros
      (Fabricius) (Hemiptera: Pentatomidae) non-parasitized (pre-parasitism) and
      parasitized (post-parasitism), which were subjected to pesticide sprays. The
      parasitism and emergence rates of T. podisi were determined classifying the
      pesticides in terms of the reduction of parasitism or emergence rates compared to
      the control. The neurotoxic insecticide cypermethrin, lambda-cyhalothrin, zeta
      cypermethrin, etofenprox, thiamethoxam, thiamethoxam + lambda-cyhalothrin,
      acetamiprid + alpha-cypermethrin, and bifenthrin + alpha-cypermethrin +
      carbosulfan were more harmful to T. podisi and, therefore, are less suitable for
      the integrated management of insect pests in irrigated rice areas.

PMID- 28439682
TI  - Cancer-Induced Bone Pain Management Through Buddhist Beliefs.
AB  - Dealing with physical pain represents a huge public health expenditure,
      especially for cancer-induced bone pain, one of the most difficult health issues,
      which impairs appetite, sleep, and mobility, negatively impacting quality of life
      and evoking mental problems. Although some literature has reported positive
      correlation between religion and pain management, there is a dearth of research
      examining the effectiveness of Buddhism on this topic. This study investigates
      the usefulness of Buddhist beliefs in managing cancer-induced bone pain through a
      case example. It illustrates how an advanced cancer patient, with the assistance
      of a counsellor, perceived pain and coped with it and pain-induced mental
      problems via Buddhist teachings and practices, including the four noble truths,
      the law of dependent origination, and karma. It offers alternative perspectives
      for helping professionals (such as physicians, nurses, counsellors, social
      workers, hospice and palliative service providers, and pain management
      practitioners) who are keen to equip themselves with a wider worldview and life
      view to better serve their clients.

PMID- 28439684
TI  - Impact of altered endogenous IgG on unspecific mAb clearance.
AB  - Immunodeficient mice are crucial models to evaluate the efficacy of monoclonal
      antibodies (mAbs). When studying mAb pharmacokinetics (PK), protection from
      elimination by binding to the neonatal Fc receptor (FcRn) is known to be a major
      process influencing the unspecific clearance of endogenous and therapeutic IgG.
      The concentration of endogenous IgG in immunodeficient mice, however is reduced,
      and this effect on the FcRn protection mechanism and subsequently on unspecific
      mAb clearance is unknown, yet of great importance for the interpretation of mAb
      PK data. We used a PBPK modelling approach to elucidate the influence of altered
      endogenous IgG concentrations on unspecific mAb clearance. To this end, we used
      PK data in immunodeficient mice, i.e. nude and severe combined immunodeficiency
      mice. To avoid impact of target-mediated clearance processes, we focussed on mAbs
      without affinity to a target antigen in these mice. In addition, intravenous
      immunoglobulin (IVIG) data of immunocompetent mice was used to study the impact
      of increased total IgG concentrations on unspecific therapeutic antibody
      clearance. The unspecific clearance is linear, whenever therapeutic IgG
      concentrations, i.e. mAb and IVIG concentrations are lower than FcRn; it can be
      non-linear if therapeutic IgG concentrations are larger than FcRn and endogenous
      IgG concentrations (e.g., under IVIG therapy). Unspecific mAb clearance of
      immunodeficient mice is effectively linear (under mAb doses as typically used in
      human). Studying the impact of reduced endogenous IgG concentrations on
      unspecific mAb clearance is of great relevance for the extrapolation to clinical
      species, e.g., when predicting mAb PK in immunosuppressed cancer patients.

PMID- 28439683
TI  - Genistein modulation of seizure: involvement of estrogen and serotonin receptors.
AB  - Genistein, a major source of phytoestrogen exposure for humans and animals, has
      been shown to mediate neuroprotection in Alzheimer's disease and status
      epilepticus. In the present study, we investigated the effect of genistein on
      pentylenetetrazole-induced seizures in ovariectomized mice and the possible
      involvement of estrogenic and serotonergic pathways in the probable effects of
      genistein. Intraperitoneal (i.p.) administration of genistein (10 mg/kg)
      significantly increased the seizure threshold 30 min prior to induction of
      seizures 14 days after ovariectomy surgery. Administration of fulvestrant (1
      mg/kg, i.p.), an estrogen receptor antagonist, completely reversed the
      anticonvulsant effect of genistein (10 mg/kg) in ovariectomized mice.
      Administration of the antagonist of serotonin receptor (5-HT3), tropisetron (10
      mg/kg, i.p.), eliminated the anticonvulsant effect of genistein, whereas co
      administration of m-chlorophenylbiguanide (5-HT3 receptor agonist; 1 mg/kg) and a
      non-effective dose of genistein (5 mg/kg) increased the seizure threshold. To
      conclude, it seems that estrogenic/serotonergic systems might be involved in the
      anticonvulsant properties of genistein.

PMID- 28439685
TI  - Histological and ultrastructural study of Myxobolus mugchelo (Parenzan, 1966)
      with initial histopathology survey of the Liza ramada host intestine.
AB  - This paper provides histological and ultrastructural data on Myxobolus mugchelo
      (Myxozoa), a parasite of the intestinal wall of thinlip mullet Liza ramada from
      the Comacchio lagoons (Northern Adriatic Sea, Italy). About 80% of the examined
      mullets were infected with this myxozoan. In histological sections, the plasmodia
      appeared rounded to ovoid and spindle shaped, measured 181.61 +/- 97 * 122.79 +/-
      53.16 MUm (mean +/- standard deviation, SD) in size. Early sporogenic plasmodia
      were located primarily in the muscle layer where no pronounced inflammatory
      response was detected. Plasmodia containing mature spores were situated closer to
      mucosal folds and were encircled by numerous immune cells, especially mast cells.
      Mature spores were generally oval and 6.06 +/- 0.40 * 3.48 +/- 0.92 MUm in size.
      The spores showed symmetrical and smooth valves. The anterior end of the spores
      contained two equal pyriform polar capsules measuring 2.19 +/- 0.47 * 1.59 +/-
      0.29 MUm. Inside the polar capsules, an isofilar polar filament displayed 5-6
      coils perpendicular or slightly oblique to the longitudinal axis. The wall of the
      polar capsule was filled with a hyaline substance contrasting with the very dense
      internal matrix. The mucus layer surrounded the spore surface. A thorough
      comparison with the Myxobolus species infecting intestine of fish is provided.
      This is the first report on occurrence of this myxozoan species in L. ramada
      population of the North Adriatic Sea.

PMID- 28439686
TI  - First case of Trichinella nativa infection in wild boar in Central Europe
      molecular characterization of the parasite.
AB  - The examination of wild boars gained in Poland shows for the first time
      occurrence of Trichinella nativa, freeze-resistant species of Trichinella in this
      host from the central Europe region. This finding is not only one of several
      cases of T. nativa invasion in wild boars all over the world but also one of the
      very few cases of T. nativa detected so far beyond the known boundary of
      occurrence of this species. The molecular characterization of discovered larvae
      based on analysis of partial genes: 5s rDNA-ISR and CO1 confirm the findings.
      Moreover, the analyzed DNA sequences of both genes present new haplotypes of T.
      nativa in comparison to that described previously.

PMID- 28439687
TI  - Colloid characterization and in situ release in shallow groundwater under
      different hydrogeology conditions.
AB  - Changes to groundwater hydrodynamics and chemistry can lead to colloid release
      that can have a major impact on the groundwater environment. To analyze the
      effects of colloid release caused by artificial groundwater recharge, field and
      laboratory tests on colloid characterization and colloid release were conducted.
      The field tests were carried out at an artificial recharge test site in Shandong
      Province. In the field investigation, one recharge water sample and five
      groundwater samples were collected and filtered through three levels of
      ultrafiltration membranes, with pore sizes of 0.45 MUm, 100 kDa, and 50 kDa. The
      field results indicated that the colloid mass concentrations in groundwater
      retained between membranes with pore sizes of 100 kDa-0.45 MUm and 50 kDa-100 kDa
      were 19 and 62 mg/L, respectively. In recharge water, the colloid mass
      concentrations retained by 100-kDa-0.45-MUm and 50-kDa-100-kDa membranes were 3
      and 99 mg/L, respectively. Colloids detected on the ultrafiltration membranes
      were mainly inorganic between 100 kDa and 0.45 MUm, and mainly organic between 50
      and 100 kDa. Based on the field colloid investigation results, the organic
      colloid was chosen in the laboratory experiments to reveal its release behavior
      under different conditions. Porous media diameter, flux, ionic strength (IS), and
      ion valence were changed to determine their influences on organic colloid
      concentration outflow from undisturbed porous media. The experiment's results
      indicate that decreasing the diameter, and increasing the flux, ionic strength,
      and the number of divalent cations, can promote organic colloid release. The
      organic colloid release rate in the early stage was high and is thus likely to
      affect the quality of groundwater. The results provide a useful scientific basis
      for minimizing changes to hydrodynamic and hydrochemical conditions during
      artificial recharge, thus safeguarding groundwater quality.

PMID- 28439688
TI  - Erratum to: Endonasal Endoscopic Surgery in the Management of Sinonasal and
      Anterior Skull Base Malignancies.

PMID- 28439689
TI  - Divergent Schwannoma-Like Phenotype in a Pleomorphic Adenoma.
AB  - The schwannoma-like pleomorphic adenoma is a rare histopathological variant of
      the pleomorphic adenoma. Five previous reports with seven cases exist in English
      language literature. These tumors present in the parotid gland most commonly.
      Intraparotid schwannomas of the facial nerve and schwannomas with glandular
      differentiation have also been reported. A 60-year-old male presented with an
      asymptomatic swelling over the left angle of the mandible. The swelling had been
      present for about 12 years with a recent increase in size. CT imaging showed a
      hyperdense circumscribed mass of the superficial lobe of the parotid. The working
      diagnosis was that of a benign tumor of salivary gland or soft tissue origin. The
      mass was excised with careful preservation of the facial nerve. The 3.5 cm mass
      was submitted for histopathological examination. The well-circumscribed,
      encapsulated mass showed a predominant sheet-like proliferation of Antoni type A
      like tissue, Foci of glandular differentiation with duct-like structures were
      also seen. Cytological atypia or mitotic activity were not seen. Nuclei of
      lesional cells diffusely and strongly expressed reactivity to p63. The final
      diagnosis was a schwannoma-like pleomorphic adenoma. No recurrence has been
      reported in the 15 months since the removal. Facial nerve function is unimpaired
      with a House Brackmann facial nerve function score of one. The potential for
      misdiagnosis in fine needle aspirate and incisional biopsies is real in cases of
      schwannoma-like pleomorphic adenoma. The diagnostic pitfalls include the
      schwannoma and leiomyoma. Schwannomas with glandular differentiation have also
      been reported and therefore a misdiagnosis may potentially occur in excised
      specimens. Careful application of immunohistochemistry may help in the
      differentiation of these lesions.

PMID- 28439690
TI  - Association of endotracheal tube repositioning and acute laryngeal lesions during
      mechanical ventilation in children.
AB  - The objective of this study is to determine the incidence of post-extubation
      acute laryngeal lesions in a pediatric intensive care unit (PICU) and potential
      risk factors. Children, aged 28 days to 5 years, admitted to the PICU who
      required endotracheal intubation for at least 24 h were enrolled. Exclusion
      criteria were a previous intubation, history of laryngeal disease, current or
      past tracheostomy, the presence of craniofacial malformations and patients
      considered on palliative care. All patients underwent flexible fiber-optic
      laryngoscopy (FFL) not later than 8 h after extubation. A blinded researcher
      identified and classified laryngeal lesions based on recorded media. 231 children
      were enrolled between November 2005 and December 2015. At FFL examination, 102
      children (44.15%) presented moderate to severe laryngeal lesions. On a
      multivariable analysis, we found that for each additional day with repositioning
      of the endotracheal tube, there was an increase of 7.3% (RR 95% CI 1.012-1.137; P
      = 0.018) on the baseline risk of developing moderate to severe acute laryngeal
      lesions. Furthermore, for each additional dose of sedation per day of intubation,
      there was also an increase of 3.5% on the same baseline risk (RR 95% CI 1.001
      1.070; P = 0.041). The amount of tube repositioning episodes and the need for
      extra doses of sedation (as a proxy for possible agitation) were found to be
      associated with acute laryngeal lesions. Adequate sedation and minimized tube
      repositioning should be pursued to possibly prevent the development of post
      extubation airway compromise.

PMID- 28439691
TI  - Comparison of endoscopic and microscopic tympanoplasty.
AB  - Tympanoplasty was conventionally performed using a microscope for decades.
      However, since the endoscope began to be used in middle ear surgery in the 1970s,
      endoscopic tympanoplasty has gained increasing attention. The main objective of
      this study was to compare endoscopic and microscopic tympanoplasty with and
      without ossiculoplasty, demonstrating the potential advantages, disadvantages,
      and outcomes of each. This retrospective study included 126 patients with chronic
      otitis media who received tympanoplasty from 2013 to 2015 in our hospital. The
      clinical follow-up continued for at least 3 months postoperatively. Otoscopy and
      audiometry were conducted before and after the procedure. The different variables
      affecting surgical outcomes were thoroughly documented in each case. A total of
      126 patients (131 ears) were included in this retrospective study. Moreover, 74
      and 57 ears underwent endoscopic and microscopic tympanoplasty, respectively. The
      overall endoscopic tympanoplasty graft uptake rate was 97.7% (128/131). The
      operation time was significantly shorter in the endoscopic group statistically. A
      paired t test was used to compare pre- and postoperative audiometry results and
      showed significant differences between the endoscopic and microscopic groups.
      However, no statistically significant difference was observed in audiometry
      improvement between the two groups. No major complications were observed in any
      of the patients. Our study demonstrated that endoscopic tympanoplasty can be
      feasibly applied in middle ear surgery. The success rate, audiometry improvement,
      and complication rate are comparable between endoscopic tympanoplasty and
      conventional microscopic tympanoplasty. Moreover, the endoscopic group had
      smaller operation wounds and lower medical expenditures.

PMID- 28439692
TI  - The presence and prognostic significance of human papillomavirus in squamous cell
      carcinoma of the larynx.
AB  - The aim of the present study was to evaluate the role of HPV in laryngeal
      squamous cell carcinoma and correlate it with patients' clinicopathological data.
      In total, 78 laryngeal squamous cell carcinoma patients enrolled in this study.
      The presence of genotype-specific HPV DNA was evaluated using Genotyping Assay in
      formalin-fixed paraffin-embedded tissue which was diagnosed between 2005 and
      2015. All samples were also evaluated for p16 immunohistochemical staining. HPV
      DNA and p16 status were assessed in terms of location, smoking, alcohol
      consumption, lymph node status, tumor stage, overall survival, disease-free
      survival, perineural invasion, and vascular invasion retrospectively. Five test
      samples were excluded from the study due to inadequate deoxyribonucleic acid
      purity. HPV DNA was detected in 19 of 73 (26.02%) in patients with laryngeal
      squamous cell carcinoma. Human papilloma virus genotyping revealed double human
      papilloma virus in one case (types 16 and 59) and HPV 16 in the remaining cases.
      Although HPV-positive cases showed slightly better 3 years survival than HPV
      negative ones, this finding was not statistically significant (overall survival p
      = 0.417, HPV positive: 92.3%, HPV negative: 81.4%, and disease-free survival p =
      0.526, HPV positive: 93.8%, HPV negative: 80.9%). The presence of HPV DNA was not
      significantly associated with any clinicopathological features (p > 0.05). Among
      73 patients, only 4 had an immunohistochemical staining of p16 and these patients
      were also HPV DNA 16 positive. Although our study results revealed a slightly
      better survival in patients with HPV DNA positivity for HPV 16 compared to the
      negative ones, the difference was not statistically significant. However, an
      increasing rate in especially high-risk-type HPV-16 prevalence in laryngeal
      squamous cell carcinoma by RT-PCR method was observed compared to our previous
      study. Although the presence of HPV in laryngeal SCCs seems to be associated with
      slightly better prognosis, additional studies may be needed, since our results
      were not statistically significant. We believed that HPV is not an adequate
      biomarker for diagnostic and prognostic purposes in laryngeal squamous cell
      carcinoma.

PMID- 28439693
TI  - Hyperplasia and the degree and activity of inflammation in chronic recurrent
      tonsillitis: a histopathological study.
AB  - Postoperative haemorrhage following tonsillectomy occurs in 5.98% of all cases
      with up to 10 deaths reported annually in Germany. When comparing tonsillectomy
      (TE) and tonsillotomy (TT), the same long-term frequency of ENT infections is
      displayed in children and young adults. However, taking postoperative
      haemorrhaging into account, TT is more favourable. Chronic tonsillitis is one of
      the most common indications for TE in the adult population; however, a
      histopathological characterization may reveal objective criteria and provide a
      foundation for routinely performing TT in adults too. Three essential parameters
      hyperplasia (HP), grade of inflammation (GOI) and activity of inflammation (AOI),
      which are responsible for, and associated with a clinically relevant disease were
      histopathologically examined in the tonsils of 100 adult patients with chronic
      recurrent tonsillitis. The parameters were analysed and compared separately in
      the pharyngeal and basal parts of the tonsils as well as in three sections (upper
      and lower pole of the tonsil, middle part) as this may influence the indication
      for TT. The comparison of the basal and pharyngeal portions displayed a
      significant difference in the GOI and the HP in all three sections: grade 2 HP as
      well as GOI were more commonly found in the basal than pharyngeal portions (p >
      0.001). AOI (grade 2) displayed the same properties in the middle section (p <
      0.002), but did not reach statistical significance in the cranial and caudal
      sections (p = 0.107 and p = 0.186). An overabundance of grade 1 GOI, AOI, and HP
      was seen in the pharyngeal sections. The results show that two out of three
      relevant parameters that demonstrate histopathological changes in recurrent
      inflamed tonsils have a significantly stronger presence in the basal section of
      the tonsil as opposed to the pharyngeal section. The processes initiated by
      inflammation next to the surface responsible for a clinically relevant recurrent
      tonsillitis seem to cause stronger reactions in the deep follicular portion of
      the tonsils.

PMID- 28439694
TI  - Modifications to a 3D-printed temporal bone model for augmented stapes fixation
      surgery teaching.
AB  - Functional outcomes and complications in otosclerosis surgery are governed by the
      surgeon's experience. Thus, teaching the procedure to residents to guide them
      through the learning process as quickly as possible is challenging. Artificial 3D
      printed temporal bones are replacing cadaver specimens in many institutions to
      learn mastoidectomy, but these are not suitable for middle ear surgery training.
      The goal of this work was to adapt such an artificial temporal bone to aid the
      teaching of otosclerosis surgery and to evaluate this tool. We have modified a
      commercially available 3D-printed temporal bone by replacing the incus and stapes
      of the model with in-house 3D-printed ossicles. The incus could be attached to a
      6-axis force sensor. The stapes footplate was fenestrated and attached to a 1
      axis force sensor. Six junior surgeons (residents) and seven senior surgeons
      (fellows or consultants) were enrolled to perform piston prosthesis placement and
      crimping as performed during otosclerosis surgery. The time required to perform
      the tasks and the forces applied to the incus and stapes were collected and
      analyzed. No statistically significant differences were observed between the
      junior and senior groups for time taken to perform the tasks and the forces
      applied to the incus during crimping and placement of the prosthesis. However,
      significantly lower forces were applied to the stapes by the senior surgeons in
      comparison with the junior surgeons during prosthesis placement (junior vs senior
      group, 328 +/- 202.9 vs 80 +/- 99.6 mN, p = 0.008) and during prosthesis crimping
      (junior vs senior group, 565 +/- 233 vs 66 +/- 48.6 mN, p = 0.02). We have
      described a new teaching tool for otosclerosis surgery based on the modification
      of a 3D-printed temporal bone to implement force sensors on the incus and stapes.
      This tool could be used as a training tool to help the residents to self-evaluate
      their progress with recording of objective measurements.

PMID- 28439695
TI  - Usefulness of telomere length in DNA from human teeth for age estimation.
AB  - Age estimation is widely used to identify individuals in forensic medicine.
      However, the accuracy of the most commonly used procedures is markedly reduced in
      adulthood, and these methods cannot be applied in practice when morphological
      information is limited. Molecular methods for age estimation have been
      extensively developed in the last few years. The fact that telomeres shorten at
      each round of cell division has led to the hypothesis that telomere length can be
      used as a tool to predict age. The present study thus aimed to assess the
      correlation between telomere length measured in dental DNA and age, and the
      effect of sex and tooth type on telomere length; a further aim was to propose a
      statistical regression model to estimate the biological age based on telomere
      length. DNA was extracted from 91 tooth samples belonging to 77 individuals of
      both sexes and 15 to 85 years old and was used to determine telomere length by
      quantitative real-time PCR. Our results suggested that telomere length was not
      affected by sex and was greater in molar teeth. We found a significant
      correlation between age and telomere length measured in DNA from teeth. However,
      the equation proposed to predict age was not accurate enough for forensic age
      estimation on its own. Age estimation based on telomere length in DNA from tooth
      samples may be useful as a complementary method which provides an approximate
      estimate of age, especially when human skeletal remains are the only forensic
      sample available.

PMID- 28439696
TI  - Back to the Future - Part 1. The medico-legal autopsy from ancient civilization
      to the post-genomic era.
AB  - Part 1 of the review "Back to the Future" examines the historical evolution of
      the medico-legal autopsy and microscopy techniques, from Ancient Civilization to
      the Post-Genomic Era. In the section focusing on "The Past", the study of
      historical sources concerning the origins and development of the medico-legal
      autopsy, from the Bronze Age until the Middle Ages, shows how, as early as 2000
      BC, the performance of autopsies for medico-legal purposes was a known and
      widespread practice in some ancient civilizations in Egypt, the Far East and
      later in Europe. In the section focusing on "The Present", the improvement of
      autopsy techniques by Friedrich Albert Zenker and Rudolf Virchow and the
      contemporary development of optical microscopy techniques for forensic purposes
      during the 19th and 20th centuries are reported, emphasizing, the regulation of
      medico-legal autopsies in diverse nations around the world and the publication of
      international guidelines or best practices elaborated by International Scientific
      Societies. Finally, in "The Future" section, innovative robotized and advanced
      microscopy systems and techniques, including their possible use in the bio
      medicolegal field, are reported, which should lead to the improvement and
      standardization of the autopsy methodology, thereby achieving a more precise
      identification of natural and traumatic pathologies.

PMID- 28439697
TI  - Heart transplantation for adults with congenital heart disease: current status
      and future prospects.
AB  - Increased survival rates after corrective or palliative surgery for complex
      congenital heart disease (CHD) in infancy and childhood are now being coupled
      with increased numbers of patients who survive to adulthood with various residual
      lesions or sequelae. These patients are likely to deteriorate in cardiac function
      or end-organ function, eventually requiring lifesaving treatment including heart
      transplantation. Although early and late outcomes of heart transplantation have
      been improving for adult survivors of CHD, outcomes and pretransplant management
      could still be improved. Survivors of Fontan procedures are a vulnerable cohort,
      particularly when single ventricle physiology fails, mostly with protein-losing
      enteropathy and hepatic dysfunction. Therefore, we reviewed single-institution
      and larger database analyses of adults who underwent heart transplantation for
      CHD, to enable risk stratification by identifying the indications and outcomes.
      As the results, despite relatively high early mortality, long-term results were
      encouraging after heart transplantation. However, further investigations are
      needed to improve the indication criteria for complex CHD, especially for failed
      Fontan. In addition, the current system of status criteria and donor heart
      allocation system in heart transplantation should be arranged as suitable for
      adults with complex CHD. Furthermore, there is a strong need to develop
      ventricular assist devices as a bridge to transplantation or destination therapy,
      especially where right-sided circulatory support is needed.

PMID- 28439698
TI  - Synergistic effects of cigarette smoking and varicocele on semen parameters in
      715 patients.
AB  - OBJECTIVE: To evaluate whether there is a synergistic effect of varicocele and
      smoking status on semen parameters. METHODS: A retrospective evaluation of 715
      men attending an infertility clinic between 2001 and 2009 was carried out. The
      presence of a varicocele was determined by clinical examination and cigarette
      smoking habits were documented allowing patients to be divided into 4 groups: non
      smokers (n = 369), mild smokers (n = 186, 1-10 cigarettes/day), moderate smokers
      (n = 129, 10-20 cigarettes/day) and heavy smokers (n = 31, over 20
      cigarettes/day). Semen samples were harvested according to the World Health
      Organization (WHO) guidelines. Additionally, serum luteinizing hormone (LH), free
      testosterone and follicle stimulating hormone (FSH) levels were measured in all
      patients. Multivariate analysis of variance (MANOVA) was carried out and further
      corroborated with the non-parametric Kruskal-Wallis and Mann-Whitney U-tests. A p
      value of <0.05 was considered statistically significant. RESULTS: The median
      patient age was 30.2 years. Overall there was a statistically significant
      negative effect of higher varicocele grade on sperm motility and concentration (p
      < 0.05) and a significant negative effect of smoking status on sperm morphology
      and motility (very progressive, p < 0.01) as well as a significant synergistic
      effect of varicocele and smoking status on motility (p = 0.03). In the group of
      patients smoking less than 10 cigarettes per day no significant synergistic
      effect on semen parameters could be proven compared to patients with varicocele
      who did not smoke. CONCLUSIONS: We could show a significant synergistic effect of
      smoking status (>10 cigarettes) in patients with varicocele on sperm morphology
      and motility. These findings could play an important role in counselling
      infertile patients presenting with varicocele and severe smoking to improve their
      semen quality parameters if they stop smoking. Past smoking history was not
      investigated.

PMID- 28439699
TI  - Role of hematological parameters in prediction of complicated appendicitis.

PMID- 28439700
TI  - Filgrastim-alone versus pegylated filgrastim-alone for autologous peripheral
      blood stem cells mobilization in newly diagnosed multiple myeloma patients.
AB  - BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is the
      recommended standard upfront treatment for transplant eligible myeloma patients.
      Considering possible complications related to chemotherapy-cytokine mobilization,
      cytokine-alone mobilization is often used. We compared mobilization with
      filgrastim alone to pegfilgrastim alone in newly diagnosed myeloma patients after
      induction treatment with bortezomib and dexamethasone. The comparison was made
      between peripheral blood stem cell (PBSC) yields, number of apheresis,
      hematopoietic stem cell subsets, and time to neutrophil and platelet engraftment
      after aHSCT. METHODS: A total of 42 myeloma patients were prospectively enrolled
      in the study: 21 received filgrastim, 21 pegfilgrastim. Flow cytometry was used
      to determine the number of PBSC, myeloid, lymphoid, and megakaryocyte precursors
      in peripheral blood and apheresis product on day 1 of apheresis. RESULTS: The
      median number of collected PBSC was 5.05 * 106/kg in the filgrastim and 4.66 *
      106/kg in the pegfilgrastim group (p = 0.428). The median number of apheresis was
      2.5 in the filgrastim and 2 in the pegfilgrastim group (p = 0.901). The number of
      megakaryocyte precursors in peripheral blood was significantly higher in the
      filgrastim group, but not in the apheresis products. There were no statistically
      significant differences in the myeloid and lymphoid precursors in the peripheral
      blood and in the apheresis products. The median time to neutrophil and platelet
      engraftment was 13 days and 16.5 days for filgrastim and 13 days and 16 days for
      pegfilgrastim group. CONCLUSIONS: We can conclude that pegfilgrastim alone is at
      least equally successful as filgrastim alone for the PBSC mobilization in newly
      diagnosed myeloma patients.

PMID- 28439701
TI  - The influence of different sets of surgical instrumentation in Oxford UKA on
      bearing size and component position.
AB  - INTRODUCTION: The Oxford unicompartmental knee arthroplasty (OUKA) has been
      proven to be an effective treatment for anteromedial osteoarthritis of the knee
      joint. New instrumentation has been introduced to improve the reproducibility of
      implant positioning and to minimize bone loss during tibial resection (Oxford
      Microplasty; Zimmer Biomet, Warsaw, Indiana, USA). METHODS: To assess the effect
      of the new instrumentation, we retrospectively evaluated the postoperative
      radiographs and surgical records of 300 OUKAs in three consecutive cohorts of
      patients. The first cohort consists of the first 100 minimal invasive
      implantations of the OUKA using the conventional phase III instrumentation, the
      second cohort consists of the 100 most recent minimal invasive OUKA with the
      conventional phase III instrumentation and the third cohort consists of the first
      100 minimal invasive OUKA using the new Oxford Microplasty instrumentation.
      RESULTS: Mean bearing thickness was statistically significant and lower in OUKA
      with use of the updated instrumentation than with the conventional
      instrumentation (p = 0.01 and p = 0.04). Additionally, statistically significant
      and more femoral components were aligned within the accepted range of tolerance
      in both the coronal and the sagittal plane with use of the updated
      instrumentation compared to the conventional phase III instrumentation in group A
      (p = 0.029 and p = 0.038) and in the sagittal plane with use of the updated
      instrumentation compared to the conventional phase III instrumentation in group B
      (p = 0.002). CONCLUSION: The new modified instrumentation seems to be an
      effective tool to reduce the risk of malalignment of the femoral component in the
      coronal and in the sagittal plane compared to the conventional phase III
      instrumentation. Furthermore, the instrumentation is also effective in
      determining an adequate level of tibial resection and thus avoiding unnecessary
      bone loss.

PMID- 28439702
TI  - A comparison of apixaban and dabigatran etexilate for thromboprophylaxis
      following hip and knee replacement surgery.
AB  - INTRODUCTION: Patients who have undergone hip or knee replacement surgery are
      exposed to a high risk of developing a post-operative venous thromboembolus and
      so have a need for an effective, medication-based, thrombosis prophylaxis. New
      orally active anticoagulants have been available for a few years now. These
      specific substances directly block either thrombin (e.g., dabigatran etexilate)
      or Factor Xa (e.g., apixaban). It is not clear whether there are any efficacy
      differences between these two substances because there have never been any head
      to-head studies carried out. MATERIALS AND METHODS: We have carried out a study
      comparing two new orally active anticoagulants dabigatran etexilate (Pradaxa(r))
      and apixaban (Eliquis(r)) that were each given to two groups of 200 patients
      respectively, who had undergone elective hip or knee arthroplasty (100 each).
      Each patient was assessed for pre- and post-operative hemoglobin concentrations,
      post-operative blood loss, the number of transfused erythrocyte concentrates, the
      duration of wound secretion, clinical thromboembolic complications (deep vein
      thrombosis, pulmonary embolism, myocardial infarct), as well as gastrointestinal,
      intracranial or wound-related bleeding complications. RESULTS: Dabigatran
      etexilate treatment led to a significant increase in the duration of wound
      secretion in both arthroplasty groups when compared to apixaban: wound secretion
      lasted 1.2 days longer on average in the dabigatran etexilate group than in the
      apixaban group (4.1 +/- 2.1 vs. 2.9 +/- 1.8 days). There were no significant
      differences observed between the two anticoagulant groups when comparing pre- and
      post-operative Hb values, post-operative blood loss and the other clinical
      parameters. CONCLUSIONS: Thus, it appears that the direct thrombin inhibitor,
      dabigatran etexilate, is associated with a longer period of wound secretion
      following the implantation of hip and knee endoprostheses than that associated
      with the Factor Xa inhibitor, apixaban.

PMID- 28439703
TI  - The impact of direct vertebral rotation (DVR) on radiographic outcome in surgical
      correction of idiopathic scoliosis.
AB  - INTRODUCTION: Recent developments of spinal instruments allow to address nearly
      all components of idiopathic scoliosis. Direct vertebral rotation (DVR) maneuver
      was introduced to correct apical axial vertebral rotation. It is however still
      not well established how efficiently DVR affects results of scoliosis correction.
      The object of the study was to evaluate en bloc apical vertebral rotation (DVR)
      and its impact on coronal and sagittal correction of the spine in patients
      undergoing surgical scoliosis treatment. MATERIALS AND METHODS: Thirty-six
      consecutive patients who underwent posterior spinal fusion with pedicle screws
      only constructs for idiopathic scoliosis. Fifteen patients (20 curves) were
      corrected by rod derotation only and 21 patients (26 curves) had both rod
      derotation and DVR. Curve measurements were performed on x-rays obtained before
      and postoperatively-coronal curves, kyphosis (T2-T12, T5-T12). Spine flexibility
      was assessed on prone bending x-rays. Apical axial rotation was determined on CT
      scans obtained intraoperatively and postoperatively. Rotation angle (RAsag) was
      measured according to Aaro and Dahlborn. RESULTS: We observed reduction of RAsag
      in all patients; however, in DVR group, decrease was greater, by 31.8% comparing
      to non-DVR group, by 8.6% (p = 0.0003). Mean coronal correction in DVR group was
      68.8% and in rod derotation group without DVR 55% (p = 0.002). No significant
      correlation was found between degree of derotation obtained and coronal
      correction. In DVR group T2-T12 kyphosis has increased in 28 (65%) patients
      whereas in non-DVR group in 31 (69%) cases. Mean value of T2-T12 kyphosis growth
      was 16.7% in DVR and 22.1% in non-DVR group. These differences however did not
      occur statistically significant. CONCLUSIONS: Direct vertebral rotation (DVR)
      maneuver reduces significantly apical rotation of the spine, enhances ability of
      coronal correction, and it does not reduce thoracic kyphosis.

PMID- 28439704
TI  - Treatment of type B pelvic fracture using anterior subcutaneous internal fixator
      with triple pedicle screws: a new surgical technique.
AB  - INTRODUCTION: To evaluate the clinical outcomes of anterior subcutaneous internal
      fixator using triple pedicle screws (ASIF/TPS) in the treatment of unstable type
      B pelvic fracture compared with open reduction internal fixation (ORIF).
      MATERIALS AND METHODS: This was a retrospective cohort study of 26 patients with
      type B unstable fractures that underwent ASIF/TPS and 26 similar patients that
      underwent ORIF using plates and screws. Intraoperative blood loss, operating
      time, and post operation hospitalization duration were compared. Anteroposterior,
      inlet, and outlet X-rays and 3D computed tomography were obtained. Pain,
      numbness, sexual dysfunction, and activity were evaluated at every follow-up
      visit until the implants were removed. The Majeed score was used to assess the
      clinical and radiological outcomes. RESULTS: Blood loss, operating time, and
      hospitalization duration were less (all P < 0.001) in the ASIF/TPS group compared
      with the ORIF group. The clinical and radiological outcomes of the ASIF/TPS group
      after a mean follow-up of 6 months were excellent and good in 80.8%, and moderate
      in 19.2%. In comparison, the results of the ORIF group were excellent and good in
      65.4%, moderate in 29.0%, and poor in 5.6%. No patient experienced nonunion,
      delayed union, superficial infection, or deep surgical wound infection. No
      urethral injury or dysuria occurred in the ASIF/TPS group. Two patients had
      temporary lateral femoral cutaneous nerve numbness after operation. There were
      two superficial wound infections in the ORIF group. CONCLUSIONS: The use of
      ASIF/TPS with triple pedicle screws could be a reasonable option for the
      treatment of type B unstable pelvic fractures.

PMID- 28439705
TI  - Cementless Oxford medial unicompartimental knee replacement: an independent
      series with a 5-year-follow-up.
AB  - PURPOSE: Cemented unicompartmental knee replacement (UKR) has proven excellent
      long-term survival rates and functional scores in Price et al. (Clin Orthop Relat
      Res 435:171-180, 2005), Price and Svard (Clin Orthop Relat Res 469(1):174-179,
      2011) and Murray et al. (Bone Joint Surg Br 80(6):983-989, 1998). The main causes
      for revision, aseptic loosening and pain of unknown origin might be addressed by
      cementless UKR in Liddle et al. (Bone Joint J 95-B(2):181-187, 2013), Pandit et
      al. (J Bone Joint Surg Am 95(15):1365-1372, 2013), National Joint Registry for
      England, Wales and Northern Ireland: 10th Annual Report 2013 (
      http://www.njrcentre.org.uk/njrcentre/Portals/0/Documents/England/Reports/10th_an
      ual_report/NJR%2010th%20Annual%20Report%202013%20B.pdf , 2013), Swedish Knee
      Arthroplasty Register: Annual Report 2013 (
      http://www.myknee.se/pdf/SKAR2013_Eng.pdf , 2013). METHODS: This single-centre
      retrospective cohort study reports the 5-year follow-up results of our first 30
      consecutively implanted cementless Oxford UKR (OUKR). Clinical outcome was
      measured using the OKS, AKSS, range of movement and level of pain (visual
      analogue scale). The results were compared to cemented OUKR in a matched-pair
      analysis. RESULTS: Implant survival was 89.7%. One revision each was performed
      due to tibial fracture, progression of osteoarthritis (OA) and inlay dislocation.
      The 5-year survival rate of the cementless group was 89.7% and of the cemented
      group 94.1%. Both groups showed excellent postoperative clinical scores.
      CONCLUSIONS: Cementless fixation shows good survival rates and clinical outcome
      compared to cemented fixation.

PMID- 28439706
TI  - CKS1BP7, a Pseudogene of CKS1B, is Co-Amplified with IGF1R in Breast Cancers.
AB  - Pseudogenes have been reported to exhibit functional roles. Amplification or
      overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in
      various human cancers. But it was known little about CKS1B pseudogene 7
      (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The
      aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and
      address its potential roles in breast cancer. We detected copy numbers of CKS1BP7
      and insulin-like growth factor 1 receptor (IGF1R) using quantitative multi-gene
      fluorescence in situ hybridization (QM-FISH) technique, compared their status in
      both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the
      same tumors, and investigated the associations of CNAs with tumor features and
      patients outcomes. Amplification of CKS1BP7 (dot-like pattern) was found in 28.8%
      of all cases, while amplified IGF1R (cluster pattern) was identified in 24.2% of
      all patients. The two events often co-existed (p = 0.01). Within the same tumors,
      identical CNAs of CKS1BP7 and IGF1R were found in DCIS and invasive carcinoma.
      Moreover, amplification of both genes was more frequent in aneuploidy tumors and
      the tumors with high ki67, but wasn't associated with patients' outcome. In
      summary, CKS1BP7 amplification is a frequent event in breast cancer and often co
      occurs with amplified IGF1R, which provides evidence supporting the interactions
      between CKS1BP7 and IGF1R during mammary carcinogenesis. Our findings suggest
      that CKS1BP7 as well as IGF1R may serve as potential biomarkers for early
      detection and predict prognosis in breast cancer.

PMID- 28439707
TI  - Protective Role of N-Acetylcysteine on Isoprenaline-Induced Myocardial Injury:
      Histological, Immunohistochemical and Morphometric Study.
AB  - Several researchers studied the protective effect of the N-acetylcysteine (NAC)
      when it was given before the induction of myocardial infarction (MI). Other
      researchers studied such protective effect when it was before done and after done
      of the MI. The missing data are the comparison between the protective effect of
      NAC before myocardial injury with its protective effect both before and after
      myocardial injury. The aim of the study was to compare the cardioprotective
      effect of NAC on the isoprenaline-induced myocardial injury before the
      isoprenaline (ISP) injection with its protective effect both before and after the
      ISP injection. This study was applied over both short and long time periods. A
      total of 90 male adult Wistar albino rats were used in the study. The rats were
      divided into four groups: control group, ISP-treated group, NAC-pretreated group
      and NAC-pre-& posttreated group. Based on the duration of the experiment, the
      second and third groups were further subdivided into a and b groups.
      Histological, immunohistochemical and histomorphometric analysis were used. The
      myocytes in the ISP-treated groups were fragmented, disrupted with karyolysis.
      The blood vessels were dilated, congested and associated with blood
      extravasation, interstitial edema and cellular inflammatory infiltration. Much
      improvement was observed in the NAC-pretreated group. Focal degeneration was
      detected in the muscle fibers. The capillaries were normal. Minimal blood
      extravasation and cellular infiltration were seen. The cardiac muscle fibers in
      the NAC-pre-& posttreated group were regularly arranged. The mean collagen fiber
      area percent of the ISP-treated groups was significantly higher by 8.3-folds and
      10.1-folds as compared with that of the control group and was also higher by 5.5
      folds and 6.8-folds as compared with that of the NAC-pre-&posttreated groups. The
      alpha-SMA area percent in the ISP-treated groups was significantly higher by 12.2
      folds and 23.9-folds as compared with that of the control group and was higher by
      7.5-folds and 15-folds as compared with that of the NAC-pre-& posttreated groups.
      The mean PCNA area percent of the ISP-treated groups was significantly higher by
      126.2 and 164.8% as compared with that of the control group and was higher by
      106.3 and 141.5% as compared with that of NAC-pre-& posttreated groups. ISP had
      deleterious effects on the heart. Administration of NAC before ISP injection
      could largely reduce the ISP-induced short- and long-term alterations. The
      protection was maximum with the use of NAC before the ISP injection and continued
      after the injection for 12 days.

PMID- 28439708
TI  - Hepatitis B virus infection assessed 3 to 18 years after vaccination in Cuban
      children and adolescents born to HBsAg-positive mothers.
AB  - Thirty-two participants, aged between 3-18 years, born to hepatitis B surface
      antigen (HBsAg)-positive mothers and vaccinated at birth were analyzed for
      hepatitis B virus (HBV) infection. Overall, 56% had anti-HB titers >=10 IU/L;
      five were positive for antibodies to the core antigen (anti-HBc), and two of
      these were also positive for HBsAg/DNA. One of the HBsAg/anti-HBc double-negative
      children presented with an unusual occult infection (HBV DNA-positive). No known
      vaccine escape mutations were detectable. Our data suggest that the vaccine
      protected 93.8% of children in this high-risk group against chronic HBV
      infection. Occult infections should be considered even in countries with low
      endemicity and high vaccination coverage.

PMID- 28439709
TI  - Complete genome sequence and phylogenetic analyses of an aquabirnavirus isolated
      from a diseased marbled eel culture in Taiwan.
AB  - An aquabirnavirus was isolated from diseased marbled eels (Anguilla marmorata;
      MEIPNV1310) with gill haemorrhages and associated mortality. Its genome segment
      sequences were obtained through next-generation sequencing and compared with
      published aquabirnavirus sequences. The results indicated that the genome
      sequence of MEIPNV1310 contains segment A (3099 nucleotides) and segment B (2789
      nucleotides). Phylogenetic analysis showed that MEIPNV1310 is closely related to
      the infectious pancreatic necrosis Ab strain within genogroup II. This genome
      sequence is beneficial for studying the geographic distribution and evolution of
      aquabirnaviruses.

PMID- 28439710
TI  - Application of gold nanoparticle-assisted PCR for equine herpesvirus 1 diagnosis
      in field samples.
AB  - Equine herpesvirus 1 (EHV-1) is one of the most significant pathogens that
      affects equine species worldwide, causing sporadic abortion, neonatal deaths,
      chorioretinopathy, as well as neurological and upper respiratory tract diseases.
      Currently, conventional PCR targeting different genes is used widely for the
      molecular detection of EHV-1, but the low viral titer in some clinical samples
      can lead to false negative results. In this study, we aimed to assess gold
      nanoparticle (GNP)-assisted PCR as an inexpensive, highly efficient, and
      sensitive method for the detection of EHV-1, and to compare its results with
      conventional PCR and real-time quantitative PCR (qPCR). Out of 83 field samples,
      28.9%, 26.5%, and 15.6% were EHV-1-positive by qPCR, GNP-assisted PCR and
      conventional PCR, respectively. All three techniques specifically target the
      viral glycoprotein B gene. The optimized GNP-assisted PCR showed no cross
      reactivity with EHV-1-negative samples (diagnosed by qPCR). GNP-assisted PCR is a
      powerful new tool for EHV-1 detection and surveillance, because of its
      simplicity, sensitivity and specificity. It can be used as an alternative to qPCR
      in laboratories that cannot afford the expense of a qPCR system.

PMID- 28439711
TI  - [Intensive care medicine in old age : The individual status is the determining
      factor].
AB  - The increasing aging of the population in highly developed countries poses a
      profound impact on intensive care services. This is illustrated by a finding from
      a large Austrian database showing that 20% of all intensive care patients are
      aged >=80 years. Age per se is not an exclusion criteria for admission to the
      intensive care unit, but older patients are frequently affected by multiple
      comorbidities and experience a decreased physiologic reserve. Due to the very
      heterogeneous population of aged patients and since no generally accepted
      criteria for admission and treatment of these patients exist, any treatment
      decision must be made taking into consideration the individual situation. The
      perspective after possible survival from a critical illness is considered as the
      most important outcome and goes far beyond the question of survival alone. Many
      old patients have the chance to return to an acceptable quality of life even
      after a life-threatening illness. However, with respect to the limitations of
      human life, it is not justified to start or prolong intensive care in elderly
      patients without a reasonable possibility of a benefit, which is not soley
      defined in terms of survival.

PMID- 28439712
TI  - Cochrane in CORR (r): Manual Therapy and Exercise for Rotator Cuff Disease.

PMID- 28439713
TI  - Personalized axillary dissection: the number of excised lymph nodes of nodal
      positive breast cancer patients has no significant impact on relapse-free and
      overall survival.
AB  - PURPOSE: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node
      dissection (ALND) for the staging of clinically node-negative breast cancer
      patients (BCP), demonstrating equivalent survival to ALND while resulting in
      reduced morbidity. ALND has remained the standard of care for the majority of BCP
      with clinical axillary metastases or metastases found on SLN biopsy. More
      recently, it is debated whether ALND could be avoided not only in SLN-negative
      BCP but also in selected SLN-positive disease or even in all patients. This
      analysis of pN+ BCP shows the impact of the number of excised lymph nodes on RFS
      and OAS adjusted by age, tumor size, intrinsic subtypes and adjuvant systemic
      therapy. METHODS: In this retrospective, multicenter cohort study, we
      investigated data from 2992 pN+ primary BCP recruited from 17 participating
      certified breast cancer centers in Germany between 2001 and 2008 within the
      BRENDA study group. RESULTS: The median number of excised lymph nodes was 17. The
      number of excised lymph nodes was neither significant for RFS (p = 0.085) nor for
      OAS (p = 0.285). Adjustments were made for age, tumor size and intrinsic
      subtypes. The most important significant parameters for RFS were intrinsic
      subtypes (p < 0.001) and tumor size (p < 0.001) and for OAS age (p < 0.001) and
      intrinsic subtypes (p < 0.001). There were no significant differences in RFS and
      OAS in any subgroup stratified by the number of excised lymph nodes. Only for
      T3/T4 tumors, there is a very small significant advantage of ALND for RFS but not
      for OAS. After adjusting in addition by guideline adherence of adjuvant systemic
      therapy (AST), intrinsic subtypes and guideline-adherent AST are the most
      important significant (p < 0.001) parameters for RFS and OAS. CONCLUSIONS: The
      number of excised lymph nodes of pN+ BCP neither correlates with RFS nor with
      OAS. Survival of pN+ BCP is primarily determined by the biology and the guideline
      adherent AST based on the corresponding intrinsic subtypes. These results support
      the omission of a radical ALND at least for pN+ patients scheduled for breast
      conserving surgery (not mastectomy), provided they receive whole breast
      irradiation and guideline-adherent AST.

PMID- 28439714
TI  - Arterial and biliary complications after living donor liver transplantation: a
      single-center retrospective study and literature review.
AB  - AIM: The mortality of patients on the waiting list for deceased donor liver
      transplantation (DDLT) is high, especially in countries where donation rates are
      low. Thus, living donor liver transplantation (LDLT) is an attractive option.
      However, compared with DDLT, LDLT is associated with increased rates of arterial
      and biliary complications. We examined the rates of complications and risk
      factors following LDLT. METHODS: We retrospectively investigated and compared the
      rates of complications of DDLT and LDLT in our institute. We also performed
      univariate and multivariate analyses to identify the independent risk factors for
      these complications. The complications and specific disadvantages of LDLT were
      reviewed and discussed. RESULTS: The incidence rate of arterial complications in
      LDLT was 6.0%, compared with 3.2% (13/441) in DDLT. A multivariate analysis
      identified low body weight (P = 0.032) as the only independent risk factor for
      hepatic artery thrombosis. The rate of all biliary complications in LDLT was
      17.3%, compared with 18.7% in DDLT. The risk factors for biliary stricture
      identified by the multivariate analysis were recurrent cholangitis and the number
      of bile ducts. The durations of hospital stay and overall survival rates were
      similar between the two groups. CONCLUSION: Given the shortage of deceased donor
      organs, we believe that LDLT is acceptable in an attempt to meet demand.

PMID- 28439715
TI  - Carcinoembryonic antigen testing after curative liver resection for synchronous
      liver metastasis of colorectal cancer: a Japanese multicenter analysis.
AB  - PURPOSE: To identify the possible roles of carcinoembryonic antigen (CEA) testing
      after liver resection for synchronous colorectal liver metastasis (CLM). METHODS:
      The subjects of this retrospective study were patients who underwent complete
      resection of primary tumors and synchronous CLM between 1997 and 2007 at 20
      institutions in Japan. We studied the associations between perioperative CEA
      levels and the characteristics of recurrence. RESULTS: Recurrence was detected
      during the median follow-up time of 52 months in 445 (73.7%) of the total 604
      patients analyzed. A postoperative CEA level >5 ng/ml was an independent
      predictor, with the highest hazard ratio (2.25, 95% confidence interval 1.29
      3.91, P = 0.004). A postoperative CEA level >5 ng/ml had a specificity of 86.2%
      and a positive predictive value of 84.2% for recurrence. Patients with a high
      postoperative CEA level had a significantly higher recurrence rate, with a
      shorter time until recurrence and a higher frequency of multiple metastatic sites
      than those with a low postoperative CEA level. Among the patients with
      recurrence, 173 (52.7%) had an elevated CEA level (>5 ng/ml) when recurrence was
      detected. CONCLUSIONS: A postoperative CEA level >5 ng/ml was an independent
      predictor of recurrence; however, CEA testing was not a reliable surveillance
      tool to identity recurrence after liver resection.

PMID- 28439716
TI  - Antipsychotic Prescribing to Patients Diagnosed with Dementia Without a Diagnosis
      of Psychosis in the Context of National Guidance and Drug Safety Warnings:
      Longitudinal Study in UK General Practice.
AB  - INTRODUCTION: Policy interventions to address inappropriate prescribing of
      antipsychotic drugs to older people diagnosed with dementia are commonplace. In
      the UK, warnings were issued by the Medicines Healthcare products Regulatory
      Agency in 2004, 2009 and 2012 and the National Institute for Health and Care
      Excellence guidance was published in 2006. It is important to evaluate the impact
      of such interventions. METHODS: We analysed routinely collected primary-care data
      from 111,346 patients attending one of 689 general practices contributing to the
      Clinical Practice Research Datalink to describe the temporal changes in the
      prescribing of antipsychotic drugs to patients aged 65 years or over diagnosed
      with dementia without a concomitant psychosis diagnosis from 2001 to 2014 using
      an interrupted time series and a before-and-after design. Logistic regression
      methods were used to quantify the impact of patient and practice level variables
      on prescribing prevalence. RESULTS: Prescribing of first-generation antipsychotic
      drugs reduced from 8.9% in 2001 to 1.4% in 2014 (prevalence ratio 2014/2001
      adjusted for age, sex and clustering within practices (0.14, 95% confidence
      interval 0.12-0.16), whereas there was little change for second-generation
      antipsychotic drugs (1.01, confidence interval 0.94-1.17). Between 2004 and 2012,
      several policy interventions coincided with a pattern of ups and downs, whereas
      the 2006 National Institute for Health and Care Excellence guidance was followed
      by a gradual longer term reduction. Since 2013, the decreasing trend in second
      generation antipsychotic drug prescribing has plateaued largely driven by the
      increasing prescribing of risperidone. CONCLUSIONS: Increased surveillance and
      evaluation of drug safety warnings and guidance are needed to improve the impact
      of future interventions.

PMID- 28439717
TI  - Negligible effect of eNOS palmitoylation on fatty acid regulation of contraction
      in ventricular myocytes from healthy and hypertensive rats.
AB  - S-palmitoylation is an important post-translational modification that affects the
      translocation and the activity of target proteins in a variety of cell types
      including cardiomyocytes. Since endothelial nitric oxide synthase (eNOS) is known
      to be palmitoylated and the activity of eNOS is essential in fatty acid-dependent
      beta-oxidation in muscle, we aimed to test whether palmitoylation of eNOS is
      involved in palmitic acid (PA) regulation of left ventricular (LV) myocyte
      contraction from healthy (sham) and hypertensive (HTN) rats. Our results showed
      that PA, a predominant metabolic substrate for cardiac beta-oxidation,
      significantly increased contraction and oxygen consumption rate (OCR) in LV
      myocytes from sham. Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME)
      or eNOS gene deletion prevented PA regulation of the myocyte contraction or OCR,
      indicating the pivotal role of eNOS in mediating the effects of PA in cardiac
      myocytes. PA increased the palmitoylation of eNOS in LV myocytes and
      depalmitoylation with 2-bromopalmitate (2BP; 100 MUM) abolished the increment.
      Furthermore, although PA did not increase eNOS-Ser1177, 2BP reduced eNOS-Ser1177
      with and without PA. Intriguingly, PA-induced increases in contraction and OCR
      were unaffected by 2BP treatment. In HTN, PA did not affect eNOS palmitoylation,
      eNOS-Ser1177, or myocyte contraction. However, 2BP diminished eNOS palmitoylation
      and eNOS-Ser1177 in the presence and absence of PA but did not change myocyte
      contraction. Collectively, our results confirm eNOS palmitoylation in LV myocytes
      from sham and HTN rats and its upregulation by PA in sham. However, such post
      transcriptional modification plays negligible role in PA regulation of myocyte
      contraction and mitochondrial activity in sham and HTN.

PMID- 28439718
TI  - The new EU General Data Protection Regulation: what the radiologist should know.
AB  - : The European Society of Radiology (ESR) informs its membership and its
      associated Institutional Members about the new General Data Protection Regulation
      (GDPR) of the European Union (EU,) which will apply from 25 May 2018.
      Radiologists and radiology departments should be prepared to comply with several
      new rules for the protection of imaging data. Although the new GDPR applies to
      all domains of the public and private sectors, some specific derogations are
      defined for data concerning health, aiming at protecting the rights of data
      subjects and confidentiality of their personal health data, whilst preserving the
      benefits of processing data, including digital images for research and public
      health purposes. Specific new obligations which healthcare providers (including
      radiologists/radiology departments) should prepare for include data access for
      patients, rules for data processing including explicit consent of the data
      subject in the absence of derogations, or technical and organisational
      safeguards. National health authorities can define exceptions and derogations
      from certain obligations by means of national law. They will also define
      sanctions in the form of penalties or fines that may be applicable for
      organisations of the public and private sector that fail to comply with the rules
      of the GDPR. MAIN MESSAGES: * Explicit consent prior to data processing will be
      necessary. * Explicit consent prior to communication of imaging data will be
      necessary. * Providing patient access to their personal data, including
      portability, will be required. * Certain derogations and exceptions exist for
      healthcare and research. * Additional specific rules may be defined by national
      law.

PMID- 28439719
TI  - Radiological imaging of teratological fetuses: what can we learn?
AB  - OBJECTIVES: To determine the advantages of radiological imaging of a collection
      of full-term teratological fetuses in order to increase their scientific and
      educational value. BACKGROUND  : Anatomical museums around the world exhibit full
      term teratological fetuses. Unfortunately, these museums are regularly considered
      as "morbid cabinets". Detailed dysmorphological information concerning the
      exhibited specimens is often lacking. Moreover, fetuses with severe and complex
      congenital anomalies are frequently diagnosed incompletely, incorrectly or not at
      all. METHODS: In order to verify diagnoses and to enrich their educational and
      scientific value, we imaged 41 out of the 72 teratological specimens present in
      the collection of our Anatomy and Pathology Museum in Nijmegen (The Netherlands)
      by means of magnetic resonance imaging (MRI) and computed tomography (CT).
      Additionally, contemporary dysmorphological insights and 3D models are
      implemented in the teratology education of medical students and residents.
      CONCLUSIONS: Full-term teratological fetuses have become increasingly rare and
      deserve a prominent place in every anatomical museum; they are suitable for
      contemporary teratological research and education. Modern radiological techniques
      markedly enhance their scientific and didactic value. TEACHING POINTS: * To
      explore the scientific and educational potential of institutionalised
      teratological collections * To understand the additional value of radiological
      imaging in diagnosing teratological specimens * To learn about the specific
      settings of MRI parameters when scanning fixed specimens * To recognise specific
      internal dysmorphology in several congenital anomalies.

PMID- 28439720
TI  - The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds.
AB  - Despite the widespread treatment of motion sickness symptoms using drugs and the
      involvement of the vestibular system in motion sickness, little is known about
      the effects of anti-motion sickness drugs on vestibular perception. In
      particular, the impact of oral promethazine, widely used for treating motion
      sickness, on vestibular perceptual thresholds has not previously been quantified.
      We examined whether promethazine (25 mg) alters vestibular perceptual thresholds
      in a counterbalanced, double-blind, within-subject study. Thresholds were
      determined using a direction recognition task (left vs. right) for whole-body yaw
      rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll
      tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005).
      There were no statistically significant changes in yaw rotation and y-translation
      thresholds. This worsening of precision could have functional implications, e.g.,
      during driving, bicycling, and piloting tasks. Differing results from some past
      studies of promethazine on the vestibulo-ocular reflex emphasize the need to
      study motion perception in addition to motor responses.

PMID- 28439721
TI  - Incidence of thromboembolic events after use of gelatin-thrombin-based hemostatic
      matrix during intracranial tumor surgery.
AB  - Association between the use of hemostatic agents made from collagen/gelatin mixed
      with thrombin and thromboembolic events in patients undergoing tumor resection
      has been suggested. This study evaluates the relationship between flowable
      hemostatic matrix and deep vein thrombosis in a large cohort of patients treated
      for brain tumor removal. The authors conducted a retrospective, multicenter,
      clinical review of all craniotomies for tumor removal performed between 2013 and
      2014. Patients were classified in three groups: group I (flowable gelatin
      hemostatic matrix with thrombin), group II (gelatin hemostatic without thrombin),
      and group III (classical hemostatic). A total of 932 patients were selected:
      tumor pathology included 441 gliomas, 296 meningiomas, and 195 metastases.
      Thromboembolic events were identified in 4.7% of patients in which gelatin matrix
      with thrombin was applied, in 8.4% of patients with gelatin matrix without
      thrombin, and in 3.6% of cases with classical methods of hemostasis. Patients
      with venous thromboembolism had an increased proportion of high-grade gliomas
      (7.2%). Patients receiving a greater dose than 10 ml gelatin hemostatic had a
      higher rate of thromboembolic events. Intracranial hematoma requiring
      reintervention occurred in 19 cases: 4.5% of cases of group III, while
      reoperation was performed in 1.3 and 1.6% of patients in which gelatin matrix
      with or without thrombin was applied. Gelatin matrix hemostat is an efficacious
      tool for neurosurgeons in cases of difficult intraoperative bleeding during
      cranial tumor surgery. This study may help to identify those patients at high
      risk for developing thromboembolism and to treat them accordingly.

PMID- 28439722
TI  - DNA methylation age-acceleration is associated with disease duration and age at
      onset in C9orf72 patients.
AB  - The repeat expansion in C9orf72 is the most common cause of amyotrophic lateral
      sclerosis and frontotemporal dementia. C9orf72 patients present with a wide range
      in disease duration and age of onset. The strongest risk factor for both
      syndromes is aging, which was linked to DNA methylation (DNAm) age based on the
      cumulative assessment of the methylation levels of 353 CpGs included on the
      genome-wide 450k BeadChip. DNAm age may reflect biological age better than
      chronological age. We conducted a genome-wide blood DNA methylation study of 46
      unrelated C9orf72 patients. After correction for multiple testing, none of the
      CpGs demonstrated association between its methylation level and disease duration
      or age of onset. However, we detected a significant reverse correlation of DNAm
      age-acceleration with disease duration and age of onset, suggesting that for
      every 5-year increase in DNAm age-acceleration there is a 3.2-year earlier age of
      onset and 1.5-year shorter disease duration. The significant correlations remain
      after adjusting for gender, TMEM106B genotypes, disease phenotype and C9orf72
      5'CpG island methylation status. A similar trend was observed for the blood DNA
      of affected members of an extended C9orf72 family; and tissues from the central
      nervous system of C9orf72 autopsy cases. For instance, regression analysis
      suggested that a 5-year increase in DNAm age-acceleration is linked to an earlier
      age of onset by 4.7 or 5.5 years for frontal cortex or spinal cord, respectively.
      Blood DNAm age may be a useful biomarker for biological age, because blood DNAm
      age-acceleration was similar to all investigated brain tissues, except for
      cerebellum that ages more slowly. In conclusion, DNA methylation analysis of
      C9orf72 patients revealed that increased DNAm age-acceleration is associated with
      a more severe disease phenotype with a shorter disease duration and earlier age
      of onset.

PMID- 28439724
TI  - Recent Developments in the Synthesis of Cyclic Carbonates from Epoxides and CO2.
AB  - The use of CO2 as a C1 building block will be of essential importance in the
      future. In this context the synthesis of cyclic carbonates from epoxides and CO2
      gained great attention recently. These products are valuable compounds in a
      variety of chemical fields. The development of new catalysts and catalytic
      systems for this atom-economic, scalable, and industrially relevant reaction is a
      highly active research field. Over the past 17 years great advances have been
      made in this area of research. This chapter covers the survey of the important
      known classes of homogeneous catalysts for the addition of CO2 to epoxides.
      Besides pioneering work, recent developments and procedures that allow this
      transformation under mild reaction conditions (reaction temperatures of <=100 
      degrees C and/or CO2 pressures of 0.1 MPa) are especially emphasized.

PMID- 28439723
TI  - Psychiatric comorbidity in alcohol use disorders: results from the German S3
      guidelines.
AB  - Alcohol use disorders (AUD) have a high comorbidity with mental disorders. Vice
      versa, alcohol consumption plays an important role in affective disorders,
      anxiety disorders, ADHD, schizophrenic psychosis, and other mental disorders. In
      developing the current interdisciplinary, evidence-based treatment guideline on
      screening, diagnostics, and treatment of AUD, available research on comorbid
      mental diseases in AUD has been compiled to generate recommendations for
      treatment. The guideline was prepared under the responsibility of the German
      Association for Psychiatry, Psychotherapy, and Psychosomatics (DGPPN) and the
      German Association for Addiction Research and Therapy (DG-Sucht). To meet the
      methodological criteria for the highest quality guidelines ("S3-criteria") as
      defined by the Association of Scientific Medical Societies in Germany (AWMF), the
      following criteria were employed: (1) a systematic search, selection, and
      appraisal of the international literature; (2) a structured process to reach
      consensus; and (3) inclusion of all relevant representatives of future guideline
      users. After assessing and grading the available literature, the expert groups
      generated several recommendations for the screening, diagnosis, and treatment of
      comorbid mental disorders. These recommendations were subdivided into psycho-,
      pharmaco-, and combination therapies. These are the first guidelines ever to make
      specific treatment recommendations for comorbid mental diseases in AUD. The
      recommendations extend to different treatment approaches including diagnostics
      and settings to present available effective and state-of-the-art treatment
      approaches to clinicians. Hitherto, many clinical constellations have not been
      addressed in research. Therefore, recommendations for future research are
      specified.

PMID- 28439725
TI  - Nutritional status of allogeneic hematopoietic stem cell transplantation
      recipients: influencing risk factors and impact on survival.
AB  - PURPOSE: Patients subjected to allogeneic hematopoietic stem cell transplantation
      (HSCT) are at increased nutritional risk which in turn may alter their outcome.
      For providing good nutritional care for patients, it is important to analyze risk
      factors influencing nutritional status during and after HSCT. METHODS: Fifty
      patients undergoing allogeneic HSCT were subjected to nutritional status
      assessment by using the patient-generated subjective global assessment (PG-SGA)
      at initial admission, day 30 and day 180. RESULTS: Two patients (4%) had
      malnutrition at admission, 36 (72%) at day 30, and 24 (48%) at day 180. At day
      30, comorbidity index higher than 0 and fever lasting for more than 1 week had a
      significant impact on nutritional status (P = .004 and P = .006, respectively).
      Regarding day 180, comorbidity index higher than 0 and presence of >=grade II
      acute gastrointestinal graft versus host disease (GI GVHD) significantly
      influenced nutritional status (P = .017 and P = .026, respectively). Well
      nourished patients at admission and day 180 had a significantly higher overall
      survival (OS) in comparison to malnourished patients (P < .001 and P = .012,
      respectively). Nutritional status at admission and day 180 had a significant
      influence on OS in multivariate analysis (P = .039 and P = .032, respectively).
      CONCLUSIONS: Allogeneic HSCT patients having high comorbidity index, developing
      prolonged fever, and experiencing >=grade II acute GI GVHD suffer from worsening
      in their nutritional status during hospitalization and after discharge. Also,
      nutritional status at admission and day 180 significantly influences their
      survival.

PMID- 28439727
TI  - Barriers to information provision regarding breast cancer and its treatment.
AB  - PURPOSE: Women with breast cancer require information about their cancer and its
      treatment during the process of treatment decision-making, yet it is unclear if
      there are barriers to information support. This study explores the experience of
      making treatment decisions in breast cancer, paying particular attention to the
      barriers experienced to the provision of information. METHODS: Using a grounded
      theory methodology, semi-structured interviews were conducted with 22 women with
      invasive breast cancer exploring the experience of treatment decision-making.
      Data was organized using ATLAS.ti software and analyzed using constant
      comparisons. RESULTS: Analysis of the data showed that barriers to cancer and
      treatment information include intrapersonal and interpersonal communication
      challenges (emotional distress, patient-provider communication, "making it
      personal," access to information) which reside at different levels of the breast
      cancer experience (individual, dyad, group, organization). A model is provided to
      depict this experience. CONCLUSIONS: Women want information about their cancer
      and its treatment and experience barriers to information provision at various
      levels. Satisfactory information provision cannot occur without addressing
      barriers at every level. Utilizing interprofessional models of care may minimize
      existing barriers to information provision and empower patients to make
      satisfying treatment decisions that are consistent with their individual wishes.

PMID- 28439726
TI  - A pilot study of patient-centered outcome assessment using PROMIS for patients
      undergoing colorectal surgery.
AB  - PURPOSE: Few studies have assessed patient-reported outcomes following colorectal
      surgery. The absence of this information makes it difficult to inform patients
      about the near-term effects of surgery, beyond outcomes assessed by traditional
      clinical measures. This study was designed to provide information about the
      effects of colorectal surgery on physical, mental, and social well-being
      outcomes. METHODS: The NIH Patient-Reported Outcomes Measurement Information
      System (PROMIS(r)) Assessment Center was used to collect patient responses prior
      to surgery and at their routine postoperative visit. Four domains were selected
      based on patient consultation and clinical experience: depression, pain
      interference, ability to participate in social roles and activities, and interest
      in sexual activity. Multilevel random coefficient models were used to assess the
      change in scores during the follow-up period and to assess the statistical
      significance of differences in trends over time associated with key clinical
      measures. RESULTS: In total, 142 patients were consented, with 107 patients
      completing pre- and postoperative assessments (75%). Preoperative assessments
      were typically completed 1 month prior to surgery (mean 29.5 days before, SD =
      19.7) and postoperative assessments 1 month after surgery (mean 30.7 days after,
      SD = 9.2), with a mean of 60.3 days between assessment dates. Patients
      demonstrated no statistically significant changes in scores for pain interference
      (-0.18 points, p = 0.80) or the ability to participate in social roles and
      activities (0.44 points, p = 0.55), but had significant decreases in depression
      scores between pre- and postoperative assessments (-1.6 points, p = 0.03) and
      near significant increases in scores for interest in sex (1.5 points, p = 0.06).
      Pain interference scores for patients with neoadjuvant chemotherapy significantly
      increased (3.5 points, p = 0.03). Scores for the interest in sex domain decreased
      (worsened) for patients with oncologic etiology (-3.7 points, p = 0.03). No other
      differences in score trends by patient characteristics were large enough to be
      statistically significant at the p < 0.05 threshold. CONCLUSION: These data
      suggest that the majority of patients quickly return to baseline physical,
      mental, and social function following colorectal surgery. This information can be
      used preoperatively to counsel patients about the typical impact of colorectal
      surgery on quality of life.

PMID- 28439728
TI  - Is color an integral part of a rich mental simulation?
AB  - Research suggests that language comprehenders simulate visual features such as
      shape during language comprehension. In sentence-picture verification tasks,
      whenever pictures match the shape or orientation implied by the previous
      sentence, responses are faster than when the pictures mismatch implied visual
      aspects. However, mixed results have been demonstrated when the sentence-picture
      paradigm was applied to color (Connell, Cognition, 102(3), 476-485, 2007; Zwaan &
      Pecher, PLOS ONE, 7(12), e51382, 2012). One of the aims of the current
      investigation was to resolve this issue. This was accomplished by conceptually
      replicating the original study on color, using the same paradigm but a different
      stimulus set. The second goal of this study was to assess how much perceptual
      information is included in a mental simulation. We examined this by reducing
      color saturation, a manipulation that does not sacrifice object identifiability.
      If reduction of one aspect of color does not alter the match effect, it would
      suggest that not all perceptual information is relevant for a mental simulation.
      Our results did not support this: We found a match advantage when objects were
      shown at normal levels of saturation, but this match advantage disappeared when
      saturation was reduced, yet still aided in object recognition compared to when
      color was entirely removed. Taken together, these results clearly show a strong
      match effect for color, and the perceptual richness of mental simulations during
      language comprehension.

PMID- 28439729
TI  - Macular morphology in former preterm and full-term infants aged 4 to 10 years.
AB  - OBJECTIVE: To analyse macular retinal and choroidal layer thickness in former
      preterm and full-term infants and to assess associated perinatal influence
      factors and functional correlation. METHODS: This prospective controlled, cross
      sectional, hospital-based study in a tertiary center of maximum care examined
      former preterm infants with a gestational age (GA) <= 32 weeks and full-term
      neonates currently aged 4 to 10 years. We investigated data from 397 infants,
      analysing total foveal retinal thickness and six distinct macular retinal layer
      and choroidal layer measurements via spectral-domain optical coherence
      tomography. Multivariable linear regression analysis was performed to investigate
      associations of layer thickness with GA and retinopathy of prematurity (ROP).
      RESULTS: Total retinal thickness in the fovea was thicker in former preterm
      infants with GA <= 28 weeks and in those with GA between 29-32 weeks compared to
      full-term infants independently of ROP. Occurrence of ROP was also associated
      with increased foveal thickness. Ganglion cell layer together with inner
      plexiform layer (GCL+IPL) was thinner in infants with GA <= 28 weeks than in full
      term infants at 1000 and 2000MUm distance from the fovea, but no association with
      ROP was present. Similar results were found for the photoreceptor layer. Total
      foveal retinal thickness was associated with low visual function. CONCLUSION:
      This study identified low gestational age and ROP occurrence as main determinants
      for foveal thickening. Furthermore, thinned GCL+IPL measurements were associated
      with lower gestational age. This study highlights the prognostic value of these
      maturity parameters influencing retinal morphology, which may affect visual
      function.

PMID- 28439646
TI  - Critical care admission following elective surgery was not associated with
      survival benefit: prospective analysis of data from 27 countries.
AB  - PURPOSE: As global initiatives increase patient access to surgical treatments,
      there is a need to define optimal levels of perioperative care. Our aim was to
      describe the relationship between the provision and use of critical care
      resources and postoperative mortality. METHODS: Planned analysis of data
      collected during an international 7-day cohort study of adults undergoing
      elective in-patient surgery. We used risk-adjusted mixed-effects logistic
      regression models to evaluate the association between admission to critical care
      immediately after surgery and in-hospital mortality. We evaluated hospital-level
      associations between mortality and critical care admission immediately after
      surgery, critical care admission to treat life-threatening complications, and
      hospital provision of critical care beds. We evaluated the effect of national
      income using interaction tests. RESULTS: 44,814 patients from 474 hospitals in 27
      countries were available for analysis. Death was more frequent amongst patients
      admitted directly to critical care after surgery (critical care: 103/4317
      patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10
      5.21]; p < 0.001). This association may differ with national income (high income
      countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At
      hospital level, there was no association between mortality and critical care
      admission directly after surgery (p = 0.26), critical care admission to treat
      complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings
      of the hospital-level analyses were not affected by national income status. A
      sensitivity analysis including only high-risk patients yielded similar findings.
      CONCLUSIONS: We did not identify any survival benefit from critical care
      admission following surgery.

PMID- 28439731
TI  - IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2
      macrophage polarization and fibroblast activation.
AB  - Inflammation resolution is important for scar formation following myocardial
      infarction (MI) and requires the coordinated actions of macrophages and
      fibroblasts. In this study, we hypothesized that exogenous interleukin-10 (IL
      10), an anti-inflammatory cytokine, promotes post-MI repair through actions on
      these cardiac cell types. To test this hypothesis, C57BL/6J mice (male, 3- to 6
      month old, n = 24/group) were treated with saline or IL-10 (50 MUg/kg/day) by
      osmotic mini-pump infusion starting at day (d) 1 post-MI and sacrificed at d7
      post-MI. IL-10 infusion doubled plasma IL-10 concentrations by d7 post-MI.
      Despite similar infarct areas and mortality rates, IL-10 treatment significantly
      decreased LV dilation (1.6-fold for end-systolic volume and 1.4-fold for end
      diastolic volume) and improved ejection fraction 1.8-fold (both p < 0.05). IL-10
      treatment attenuated inflammation at d7 post-MI, evidenced by decreased numbers
      of Mac-3-positive macrophages in the infarct (p < 0.05). LV macrophages isolated
      from d7 post-MI mice treated with IL-10 showed significantly elevated gene
      expression of M2 markers (Arg1, Ym1, and Tgfb1; all p < 0.05). We further
      performed RNA-seq analysis on post-MI cardiac macrophages and identified 410
      significantly different genes (155 increased, 225 decreased by IL-10 treatment).
      By functional network analysis grouping, the majority of genes (133 out of 410)
      were part of the cellular assembly and repair functional group. Of these,
      hyaluronidase 3 (Hyal3) was the most important feature identified by p value. IL
      10 treatment decreased Hyal3 by 28%, which reduced hyaluronan degradation and
      limited collagen deposition (all p < 0.05). In addition, in vivo IL-10 treatment
      increased fibroblast activation (proliferation, migration, and collagen
      production), an effect that was both directly and indirectly influenced by
      macrophage M2 polarization. Combined, our results indicate that in vivo infusion
      of IL-10 post-MI improves the LV microenvironment to dampen inflammation and
      facilitate cardiac wound healing.

PMID- 28439732
TI  - Skin allograft procurement and transplantation in Mashhad, Iran: Are burn
      patients' needs being met?
AB  - Only a single donor's tissue may save or improve lives of one hundred patients.
      Unfortunately, low governmental and media support of tissue procurement and
      transplantation programs is a worldwide problem. Loss of an effective tissue
      procurement program in many countries like Iran, may lead to loss of many
      thousands valuable tissues each year. To evaluate the rate of skin donation in
      Mashhad in comparison to other organs and tissues, we extracted the data related
      to tissue and organ procurement in Mashhad from 2001. Then we evaluated the
      annual skin allograft needs in the Burn Department of Imam Reza Hospital as the
      only referral burn center in the northeast of Iran. Brain dead potential donation
      rate per million populations of Mashhad in the years 2007-2014 was about 33. The
      mean refusal rate was 51%. Of patients who have consent for donation, more than
      86% have consent for skin donation. Skin allograft procured from 119 (35.5%)
      candidates. Average of skin retrieval per cadaveric was 1525 cm2 with a gradual
      increase from 1400 cm2 in the first year to 1800 cm2 in the last year. The
      recipient to donor ratio was 1.14. It is estimated that about 1 cm2 of skin
      allograft is needed for any cm2 burnt body surface area. Considering more than
      700 acute burn hospitalization in our burn unit, the patients need for skin
      allograft would be more than 3.5 million cm2, annually. The annual amount of skin
      procurement in Mashhad has been currently about 20,000 cm2. It shows that our
      patients demand is higher than supply. Skin procurement and transplantation is a
      simple procedure which can be as lifesaving as organ procurement and
      transplantation. But there isn't any national organization to regulate tissue
      procurement, banking and transplantation. Governmental support of skin
      procurement and transplantation programs especially nonprofit programs may
      improve skin procurement rate and save more lives of severely burnt patients.

PMID- 28439733
TI  - Duodenal Involvement is an Independent Prognostic Factor for Patients with
      Surgically Resected Pancreatic Ductal Adenocarcinoma.
AB  - BACKGROUND: The current staging system for pancreatic ductal adenocarcinoma
      (PDAC) includes information about size and local extension of the primary tumor
      (T stage). The value of incorporating any local tumor extension into pancreatic
      staging systems has been questioned because it often is difficult to evaluate
      tumor extension to the peri-pancreatic soft tissues and because most carcinomas
      of the head of the pancreas infiltrate the intra-pancreatic common bile duct.
      This study sought to evaluate the prognostic implications of having PDAC with
      local tumor extension. METHODS: A single-institution, prospectively collected
      database of 1128 patients who underwent surgical resection for PDAC was queried
      to examine the prognostic significance of extra-pancreatic tumor involvement ("no
      involvement," "duodenal involvement," and "extensive involvement"; e.g., gastric,
      colon or major vein involvement). RESULTS: The median overall survival for the
      patients without extra-pancreatic involvement was 26 months versus 19 months for
      the patients with duodenal involvement and 16 months for the patients with
      extensive involvement (p < 0.001). In the multivariable analysis, duodenal and
      extensive involvement independently predicted increased risk of death compared
      with no involvement (hazard ratio [HR] 1.30; 95% confidence interval [CI] 1.08
      1.57 and 1.78; 95% CI 1.25-2.55, respectively). A multivariable model combining
      duodenal and extensive extra-pancreatic involvement, tumor grade, lymph node
      ratio, and other prognostic features had the highest c-index (0.67). CONCLUSIONS:
      Inclusion of duodenal involvement in the staging of PDAC adds independent
      prognostic information.

PMID- 28439730
TI  - Physiological and therapeutic regulation of PCSK9 activity in cardiovascular
      disease.
AB  - Ischemic heart disease is the main cause of death worldwide and is accelerated by
      increased levels of low-density lipoprotein cholesterol (LDL-C). Proprotein
      convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of
      LDL-C through its ability to induce degradation of the LDL receptor (LDLR) in the
      lysosome of hepatocytes. Only in the last few years, a number of breakthroughs in
      the understanding of PCSK9 biology have been reported illustrating how PCSK9
      activity is tightly regulated at several levels by factors influencing its
      transcription, secretion, or by extracellular inactivation and clearance. Two
      humanized antibodies directed against the LDLR-binding site in PCSK9 received
      approval by the European and US authorities and additional PCSK9 directed
      therapeutics are climbing up the phases of clinical trials. The first outcome
      data of the PCSK9 inhibitor evolocumab reported a significant reduction in the
      composite endpoint (cardiovascular death, myocardial infarction, or stroke) and
      further outcome data are awaited. Meanwhile, it became evident that PCSK9 has
      (patho)physiological roles in several cardiovascular cells. In this review, we
      summarize and discuss the recent biological and clinical data on PCSK9, the
      regulation of PCSK9, its extra-hepatic activities focusing on cardiovascular
      cells, molecular concepts to target PCSK9, and finally briefly summarize the data
      of recent clinical studies.

PMID- 28439737
TI  - Erratum to: ESR1 mutations affect anti-proliferative responses to tamoxifen
      through enhanced cross-talk with IGF signaling.

PMID- 28439735
TI  - Preoperative prediction of the size of pure ductal carcinoma in situ using three
      imaging modalities as compared to histopathological size: does magnetic resonance
      imaging add value?
AB  - PURPOSE: The purpose of this study was to evaluate whether magnetic resonance
      imaging (MRI) and ultrasonography add value to traditional mammography in an
      Asian population with ductal carcinoma in situ (DCIS). METHODS: Data of 244
      patients with pure DCIS treated at Severance Hospital between 2013 and 2015 were
      analyzed retrospectively. Data extracted included age, preoperative diagnosis,
      tumor size on preoperative imaging studies, and final histopathological tumor
      type and size, including hormone receptor status. The extent of correlation
      between imaging and histopathological tumor sizes was evaluated using a variety
      of methods, including Bland-Altman analysis. RESULTS: The mean patient age was
      52.39 years (SD = 10.31). The mean measurements of the tumor on preoperative
      ultrasonography, mammography, MRI, and histopathology were 1.80 (SD = 1.23) cm,
      2.97 (SD = 1.92) cm, 2.53(SD = 1.84) cm, and 1.88 (SD = 1.36) cm, respectively.
      The mean differences in tumor size between ultrasonography, mammography, and MRI
      compared with histopathology were -0.09 (SD = 1.39), 1.09 (SD = 1.89), and 0.65
      (SD = 1.78), respectively. The correlation between the sizes was significant with
      r values for ultrasonography, mammography, and MRI of 0.447 (SE = 0.061), 0.375
      (SE = 0.042), and 0.409 (SE = 0.043), respectively. Mammography and MRI estimated
      tumor size significantly better for patients older than 50 years (p = 0.045 and
      <0.001, respectively). Mammography also provided good estimation for patients
      with a body mass index under 25 (p = 0.041). CONCLUSION: MRI is better at
      estimation of histopathological DCIS size compared with mammography. However,
      ultrasonography had better estimation compared with MRI and mammography, probably
      owing to the high breast density in this population.

PMID- 28439736
TI  - Early cardiac perfusion defects after left-sided radiation therapy for breast
      cancer: is there a volume response?
AB  - PURPOSE: Cardiac single-photon emission computed tomography (SPECT) is often used
      to identify defects in myocardial perfusion due to atherosclerotic coronary
      artery disease. It was also used in studies to evaluate radiation therapy (RT)
      associated cardiac abnormalities. In the current review, we aim to evaluate the
      rates of post-RT cardiac SPECT early perfusion abnormalities and relate this to
      the irradiated left ventricular volume. METHODS: The studies cited in this
      systematic review were identified using the preferred reporting items for
      systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: Six studies
      between 1996 and 2016 fulfilled the inclusion criteria. The reported perfusion
      defects in these studies were seen in the apical and anterolateral aspects of the
      left ventricle. Three studies show correlation between the percent of the left
      ventricle within the RT-field and percent of patients with early perfusion
      defects on cardiac SPECT. In two studies that used cardiac sparing techniques
      (such as deep inspiration), that resulted in a low mean heart dose, no perfusion
      defects were noted. CONCLUSIONS: Data suggest that incidental irradiation of the
      heart in cases of left breast/chest wall RT can result in early post-RT perfusion
      defects on cardiac SPECT. There appears to be strong dose/volume dependence to
      the risk, and hence techniques to reduce cardiac exposure are recommended.

PMID- 28439734
TI  - Myocardial salvage after primary percutaneous coronary intervention in patients
      with ST-elevation myocardial infarction presenting early versus late after
      symptom onset.
AB  - Primary percutaneous coronary intervention (PCI) is the treatment of choice in
      patients with ST-elevation myocardial infarction (STEMI) presenting within 12 h
      of symptom onset. A benefit in the subacute stage is less clear. The aim of the
      present analysis was to compare myocardial salvage and infarct size between
      patients with early and late reperfusion after STEMI. We compared cardiac
      magnetic resonance (CMR) data from a randomized controlled trial (RCT) in STEMI
      patients presenting within 12 h (n = 695) and a RCT of subacute STEMI patients
      presenting between 12 and 48 h (n = 93) after symptom onset. CMR imaging was
      performed 3.9 +/- 6.3 days after myocardial infarction. Analyses were performed
      for an unmatched cohort comprising all patients (n = 788) and a cohort matched
      for area at risk (n = 186). In the overall cohort, area at risk was similar in
      both groups [37.1 +/- 16.1% of left ventricular mass (%LV) vs. 38.3 +/- 16.2%LV;
      p = 0.50]. Compared to STEMI patients with early reperfusion, patients with late
      PCI demonstrated larger infarct size (18.0 +/- 12.5%LV vs. 28.9 +/- 16.9%LV; p <
      0.01) and higher extent of microvascular obstruction (1.5 +/- 2.9%LV vs. 2.7 +/-
      4.1%LV; p = 0.01). Myocardial salvage index was significantly smaller in patients
      with late reperfusion (52.1 +/- 25.9 vs. 27.4 +/- 26.0; p < 0.01). Analysis of
      the matched cohorts confirmed the decreased myocardial salvage (p < 0.01) and
      increased infarct size (p < 0.01) in case of late reperfusion. Compared to
      patients with timely primary PCI, late reperfusion after STEMI results in
      decreased myocardial salvage and increased infarct size. However, salvageable
      myocardium was also found in subacute stages of STEMI.

PMID- 28439738
TI  - Prospective open uncontrolled phase I study to define a well-tolerated dose of
      oral artesunate as add-on therapy in patients with metastatic breast cancer
      (ARTIC M33/2).
AB  - PURPOSE: The antimalarial drug artesunate (ART) is a promising candidate for
      cancer treatment as it displays anticancer effects in various models. While in
      short-term treatment of malaria, an excellent safety profile has been found for
      ART, the potential long-term treatment of cancer patients demands a phase I dose
      finding clinical trial determining the daily ART dose which would be well
      tolerated as add-on therapy. METHODS: Patients with metastatic breast cancer were
      to receive either 100 or 150 or 200 mg oral ART daily as add-on to their
      guideline-based oncological therapy for a study period of four weeks with
      frequent clinical and laboratory monitoring until 4-8 weeks thereafter. According
      to the statistical design, recruitment was scheduled in groups of three patients
      in order not to miss a more than 33% frequency of dose-limiting adverse events
      (DL-AE) prior to dose escalation. RESULTS: Twenty-three patients were recruited,
      and all planned dose levels were applied. During the actual trial period of 4 +/-
      1 weeks, three patients experienced six DL-AEs altogether (leucopenia,
      neutropenia, asthenia, anemia) possibly related to ART (not exceeding 33% in any
      dose level). CONCLUSIONS: Up to 200 mg/d (2.2-3.9 mg/kg/d) oral ART were safe and
      well tolerated; therefore, 200 mg/d are recommended for phase II/III trials.
      Safety monitoring should include reticulocytes, NTproBNP, as well as audiological
      and neurological exploration.

PMID- 28439739
TI  - Medical Mistrust and Colorectal Cancer Screening Among African Americans.
AB  - Despite well-documented benefits of colorectal cancer (CRC) screening, African
      Americans are less likely to be screened and have higher CRC incidence and
      mortality than Whites. Emerging evidence suggests medical mistrust may influence
      CRC screening disparities among African Americans. The goal of this systematic
      review was to summarize evidence investigating associations between medical
      mistrust and CRC screening among African Americans, and variations in these
      associations by gender, CRC screening type, and level of mistrust. MEDLINE,
      CINAHL, Web of Science, PsycINFO, Google Scholar, Cochrane Database, and EMBASE
      were searched for English-language articles published from January 2000 to
      November 2016. 27 articles were included for this review (15 quantitative, 11
      qualitative and 1 mixed methods study). The majority of quantitative studies
      linked higher mistrust scores with lower rates of CRC screening among African
      Americans. Most studies examined mistrust at the physician level, but few
      quantitative studies analyzed mistrust at an organizational level (i.e.
      healthcare systems, insurance, etc.). Quantitative differences in mistrust and
      CRC screening by gender were mixed, but qualitative studies highlighted fear of
      experimentation and intrusiveness of screening methods as unique themes among
      African American men. Limitations include heterogeneity in mistrust and CRC
      measures, and possible publication bias. Future studies should address
      methodological challenges found in this review, such as limited use of validated
      and reliable mistrust measures, examination of CRC screening outcomes beyond
      beliefs and intent, and a more thorough analysis of gender roles in the cancer
      screening process.

PMID- 28439740
TI  - Synthetic cold-inducible promoter enhances recombinant protein accumulation
      during Agrobacterium-mediated transient expression in Nicotiana excelsior at
      chilling temperatures.
AB  - OBJECTIVES: To exploit cold-inducible biochemical processes beneficial for
      foreign mRNA transcription, translation and storage, as well as protein product
      stability, during Agrobacterium-mediated transient expression. RESULTS: The
      efficiency of three different 5'-regulatory sequences to achieve transient
      expression of the GFP-based reporter gene under chilling conditions (6-8  degrees
      C since the 3rd day post inoculation) was compared. We studied the upstream
      sequences of a cold-inducible Arabidopsis thaliana cor15a gene, the core element
      of 35S CaMV promoter fused to the TMV omega 5'-UTR, and the synthetic promoter
      including the 35S core sequence and two binding sites for cold-inducible CBF
      transcription factors (P_DRE::35S). Cultivation of plants transiently expressing
      reporter gene under control of the synthetic P_DRE::35S promoter under chilling
      conditions since the 3rd dpi led to the reliably higher reporter accumulation as
      compared to the other tested regulatory sequences under chilling or greenhouse
      conditions. Reporter protein fluorescence under chilling conditions using
      P_DRE::35S reached 160% as compared to the transient expression in the
      greenhouse. Period of transient expression considerably extended if plants were
      cultivated at chilling temperature since the 3rd dpi: reporter protein
      fluorescence reached its maximum at the 20th dpi and was detected in leaves up to
      the 65th dpi. The enhanced protein accumulation at low temperature was
      accompanied by the prolonged period of corresponding mRNA accumulation.
      CONCLUSION: Transient expression under chilling conditions using synthetic cold
      inducible promoter enhances target protein accumulation and may decrease
      greenhouse heating expenses.

PMID- 28439741
TI  - Effect of Victimization on Impulse Control and Binge Drinking among Serious
      Juvenile Offenders from Adolescence to Young Adulthood.
AB  - A vast literature has found longitudinal effects of early life stress on
      substance use and self-regulatory processes. These associations may vary by
      period-specific development among youth involved in the juvenile justice system.
      The current study used an accelerated longitudinal design and auto-regressive
      latent trajectory with structure residuals (ALT-SR) model to examine the within
      person cross-lagged associations between binge drinking, impulse control, and
      victimization from 15 to 25 years of age. A large sample (N = 1100) of justice
      involved youth were followed longitudinally for 7 years (M age baseline  = 15.8,
      M age conclusion  = 22.8). In general, the sample was ethnically diverse (41%
      Black, 34% Hispanic, 21% White, 4.3% Other) and primarily male (87.2%).
      Participants reported on their frequency of binge drinking, impulse control, and
      frequency of victimization at each time point. The results indicated that, during
      adolescence, victimization and binge drinking attenuated impulse control, which
      resulted in more binge drinking and victimization during young adulthood. The
      current study highlights the importance of assessing developmental processes and
      period-specific transitions among at risk youth, especially for youth
      experiencing early life stress.

PMID- 28439742
TI  - Exploration of the binding affinities between ecdysone agonists and EcR/USP by
      docking and MM-PB/GBSA approaches.
AB  - Ecdysone receptor (EcR) is a significant target in the identification of new
      environmentally friendly pesticides. There are two types of ecdysone agonists:
      steroidal ecdysone agonists and dibenzoylhydrazines (DBHs). In this study,
      various modeling methods (homology modeling, molecular docking, MD simulation,
      binding free energy calculation, and per-residue binding free energy
      decomposition) were utilized to study the different binding mechanisms of two
      types of ecdysone agonists. Our theoretical results indicated that the relative
      binding potencies of DBHs can be ranked sufficiently accurately using the MOE
      docking method. However, MM/PBSA calculations more accurately predicted the
      binding affinities between steroidal ecdysone agonists and EcR-LBD. To identify
      the key residues involved in ecdysone agonist binding, the binding free energy
      (DeltaG Bind) was decomposed into the energy contributions of individual
      residues. The results revealed that nine residues-Ile339, Thr343, Met380, Met381,
      Tyr403, Tyr408, Asp419, Gln503, and Asn504-determined the binding affinities of
      the DBHs. Glu309, Met342, Arg383, Arg387, and Leu396 were important influences on
      the binding affinities of the steroidal ecdysone agonists. Graphical abstract The
      ecdysone receptor (EcR) is related to insect growth and has been shown to be a
      useful target for insecticides.

PMID- 28439743
TI  - Interdigital melanoma simultaneously affecting two neighboring interdigital
      spaces : First description in the medical literature.
AB  - BACKGROUND: Interdigital melanoma, as a subtype of acral lentiginous melanoma, is
      relatively uncommon in the Caucasian population. It frequently goes unrecognized
      for a prolonged period of time prior to diagnosis, due to its asymptomatic nature
      and variable clinical appearance. METHODS: We report the case of a 67-year-old
      Caucasian woman who presented with interdigital malignant melanoma affecting two
      neighboring interdigital spaces. It had evolved over a period of more than 15
      years and had been initially misdiagnosed as tinea pedis due to the macerated
      appearance of the lesion and a positive mycologic examination. RESULTS: We
      highlight the striking involvement of two adjacent interdigital spaces and the
      neighboring area of the sole of the foot by the tumor. The melanoma was staged as
      IIIC, with pathologic grading T4bN2bM CONCLUSIONS: The involvement of two
      adjacent interdigital spaces is unusual and, to our knowledge, has not been
      previously highlighted in the medical literature. It may be explained, in part,
      by the longstanding nature of the lesion in our patient.

PMID- 28439744
TI  - Change in cost after 5 years of experience with robotic-assisted hysterectomy for
      the treatment of endometrial cancer.
AB  - Health care costs are an important consideration in the decision of hysterectomy
      routes and robotic surgery is often critiqued for its high cost. We sought to
      compare the cost of robotic-assisted hysterectomies performed after initial
      acquisition of the robotic surgical system to cases performed after 5 years of
      experience. The first 20 patients at a community teaching hospital who underwent
      robotic-assisted hysterectomy for endometrial cancer by a single gynecologic
      oncology surgeon were designated Group 1 and 20 patients undergoing robotic
      hysterectomies 5 years later for the same indication were designated Group 2.
      Direct hospital costs were divided into operative and non-operative costs. Mean
      operating room cost and cost of anesthesia per minute for Group 1 were adjusted
      to Group 2 mean costs. Supply costs were adjusted using the 2015 Consumer Price
      Index. Baseline characteristics of the groups were comparable. After 5 years of
      experience, there was a 15.5% [95% CI (-$2865, -$407), p = 0.01] reduction in
      mean total costs (Group 1 = $10,543, Group 2 = $8907) and a 14.3% [95% CI (
      $2378, -$390), p <= 0.01] reduction in mean operative costs (Group 1 = $9688,
      Group 2 = $8304). Significant reductions in procedure time, operating room time,
      operating room cost, and cost of anesthesia were seen from Group 1 to Group 2.
      There were no differences in mean non-operative costs, estimated blood loss, cost
      of supplies or surgeon cost. Experience with robotic-assisted hysterectomies is
      associated with reduction in costs, which is primarily a result of reduced
      operative times. This is an important factor when considering costs related to
      robotic surgery.

PMID- 28439745
TI  - Core curriculum case illustration: placental abruption.
AB  - This is the 33rd installment of a series that will highlight one case per
      publication issue from the bank of cases available online as part of the American
      Society of Emergency Radiology (ASER) educational resources. Our goal is to
      generate more interest in and use of our online materials. To view more cases
      online, please visit the ASER Core Curriculum and Recommendations for Study
      online at: http://www.erad.org/page/CCIP_TOC .

PMID- 28439746
TI  - Plasma Phosphatidylethanolamine and Triacylglycerol Fatty Acid Concentrations are
      Altered in Major Depressive Disorder Patients with Seasonal Pattern.
AB  - Disturbances in peripheral and brain lipid metabolism, including the omega-3
      fatty acid docosahexaenoic acid (DHA), have been reported in major depressive
      disorder (MDD). However, these changes have yet to be confirmed in MDD with
      seasonal pattern (MDD-s), a subtype of recurrent MDD. The present exploratory
      study quantified plasma plasmalogen and diacyl-phospholipid species, and fatty
      acids within total phospholipids, cholesteryl esters, triacylglycerols and free
      fatty acids in non-medicated MDD-s participants (n = 9) during euthymia in summer
      or fall, and during depression in winter in order to screen for potential high
      sensitivity lipid biomarkers. Triacylglycerol alpha-linolenic acid concentration
      was significantly decreased, and myristoleic acid concentration was significantly
      increased, during winter depression compared to summer-fall euthymia. 1-stearyl-2
      docosahexaenoyl-sn-glycero-3-phosphoethanolamine, a diacyl-phospholipid
      containing stearic acid and DHA, was significantly decreased in winter
      depression. Concentrations of cholesteryl ester oleic acid and several
      polyunsaturated fatty acids between summer/fall and winter increased in
      proportion to the increase in depressive symptoms. The observed changes in lipid
      metabolic pathways in winter-type MDD-s offer new promise for lipid biomarker
      development.

PMID- 28439747
TI  - Management of Cirrhotic Patients After Successful HCV Eradication.
AB  - OPINION STATEMENT: Chronic hepatitis C (HCV) is a hepatotropic virus which, when
      untreated, can lead to progressive inflammation and fibrosis resulting in
      cirrhosis, hepatocellular carcinoma (HCC), and decompensations related to end
      stage liver disease. The relatively recent introduction of all oral, interferon
      free, direct-acting antiviral medications against HCV has transformed the
      management of these patients. Previous treatment regimens were prolonged, poorly
      tolerated, and frequently did not result in cure. Current therapies achieve
      sustained viral response (SVR) in the vast majority of patients including those
      with decompensated liver disease; a previously challenging population to treat.
      These successes will result in significant numbers of cirrhotic patients
      requiring management after SVR. Although many complications of cirrhosis are
      improved in this setting, regular follow-up of HCC, esophageal varices, and other
      sequelae of cirrhosis will be necessary. This chapter will review the management
      of cirrhosis in HCV patients achieving cure.

PMID- 28439748
TI  - Duodenal Switch Is Superior to Gastric Bypass in Patients with Super Obesity when
      Evaluated with the Bariatric Analysis and Reporting Outcome System (BAROS).
AB  - BACKGROUND: It is not clear which bariatric procedure that gives the best outcome
      for patients with super obesity (body mass index [BMI] > 50 kg/m2). This study
      aims to compare outcomes in patients with super obesity after Roux-en-Y gastric
      bypass (RYGB) and duodenal switch (BPD/DS) using the Bariatric Analysis and
      Reporting Outcome System (BAROS) and a local questionnaire for gastrointestinal
      symptoms. METHODS: A retrospective mail survey including 211 patients, 98 RYGB
      and 113 BPD/DS, with a mean follow-up time of 4 years for both groups. Gender
      distribution, age, and comorbidities were similar. Weight loss, changes in
      comorbidities, quality of life (QoL), and adverse events were registered, as well
      as gastrointestinal symptoms. RESULTS: Preoperative BMI was higher in the BPD/DS
      group (56 +/- 6.7 vs. 52 +/- 4.0 kg/m2, p < 0.01); despite this, the
      postoperative BMI was lower (31 +/- 5.5 vs. 36 +/- 7.1 kg/m2, p < 0.01). The
      effect on diabetes was superior after BPD/DS; otherwise, both groups had a
      similar reduction in comorbidities. There was no difference in QoL. Adverse
      events were less common after RYGB (14 vs. 27%). Overall, the BPD/DS group had a
      superior BAROS score (4.7 +/- 2.0 vs. 4.0 +/- 2.1, p < 0.05). Dumping was more
      common after RYGB (p < 0.01), while reflux, diarrhea, fecal incontinence, and
      problems with malodorous flatus were more common after BPD/DS (all p < 0.05).
      Frequency of nausea/vomiting and abdominal pain were similar. CONCLUSION:
      Patients with super obesity have a better weight reduction and metabolic control
      with BPD/DS, at the cost of higher incidence of adverse events, compared to
      patients operated with RYGB.

PMID- 28439749
TI  - Slippage-a Significant Problem Following Gastric Banding-a Single Centre
      Experience.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding is a well-established method
      of morbid obesity treatment. One of the complications is slippage. AIM: The aim
      of the study was to assess the prevalence, causes, and handling of slippage after
      LAGB in own material. MATERIAL AND METHODS: There were 740 procedures performed
      by one surgical team. The patients were selected according to the IFSO
      principles. The pars flaccida technique was applied and the position of the band
      was controlled. There was neither plication nor the bands were sutured to the
      stomach wall. Slippage was recognized during X-ray examination. With these
      patients, the band was emptied of liquid, gastric endoscopy was performed
      routinely, and patients were qualified for surgery. RESULTS: The patient group
      consisted of 500 women and 240 men. The average body weight was 128 kg and BMI
      44.60 kg/m2. The slippage was observed in 8.1% cases in 7.03% patients. In 1.08%,
      slippage occurred twice. The main problems reported by patients were pain, a
      significant increase of disposable food intake, vomiting, and weight gain. In a
      small group of patients, these complications were detected incidentally. All
      patients were treated surgically. In 38.33%, the band repositioning was
      performed. In 33.33%, a different surgical approach was performed. In the group
      of reoperated patients, there were no fatal cases or any severe complications.
      CONCLUSIONS: In conclusion, we believe that slippage is and will continue to be a
      significant problem in patients with gastric banding. Patient education focused
      on dietary errors may reduce the incidence of this complication. The grace period
      between the primary surgery and the redo operation should be applied regarding
      reoperation.

PMID- 28439750
TI  - Hospital heterogeneity: what drives the quality of health care.
AB  - A major feature of health care systems is substantial variation in health care
      quality across hospitals. The quality of stroke care widely varies across NHS
      hospitals. We investigate factors that may explain variations in health care
      quality using measures of quality of stroke care. We combine NHS trust data from
      the National Sentinel Stroke Audit with other data sets from the Office for
      National Statistics, NHS and census data to capture hospitals' human and physical
      assets and organisational characteristics. We employ a class of non-parametric
      methods to explore the complex structure of the data and a set of correlated
      random effects models to identify key determinants of the quality of stroke care.
      The organisational quality of the process of stroke care appears as a fundamental
      driver of clinical quality of stroke care. There are rich complementarities
      amongst drivers of quality of stroke care. The findings strengthen previous
      research on managerial and organisational determinants of health care quality.

PMID- 28439751
TI  - Development of a Streamlined Work Flow for Handling Patients' Genetic Testing
      Insurance Authorizations.
AB  - Obtaining genetic testing insurance authorizations for patients is a complex,
      time-involved process often requiring genetic counselor (GC) and physician
      involvement. In an effort to mitigate this complexity and meet the increasing
      number of genetic testing insurance authorization requests, GCs formed a novel
      partnership with an industrial engineer (IE) and a patient services associate
      (PSA) to develop a streamlined work flow. Eight genetics clinics and five
      specialty clinics at the University of Michigan were surveyed to obtain
      benchmarking data. Tasks needed for genetic testing insurance authorization were
      outlined and time-saving work flow changes were introduced including 1) creation
      of an Excel password-protected shared database between GCs and PSAs, used for
      initiating insurance authorization requests, tracking and follow-up 2)
      instituting the PSAs sending GCs a pre-clinic email noting each patients' genetic
      testing insurance coverage 3) inclusion of test medical necessity documentation
      in the clinic visit summary note instead of writing a separate insurance letter
      and 4) PSAs development of a manual with insurance providers and genetic testing
      laboratories information. These work flow changes made it more efficient to
      request and track genetic testing insurance authorizations for patients, enhanced
      GCs and PSAs communication, and reduced tasks done by clinicians.

PMID- 28439752
TI  - Mathematical Modeling of Cellular Cross-Talk Between Endothelial and Tumor Cells
      Highlights Counterintuitive Effects of VEGF-Targeted Therapies.
AB  - Tumor growth and progression are critically dependent on the establishment of a
      vascular support system. This is often accomplished via the expression of pro
      angiogenic growth factors, including members of the vascular endothelial growth
      factor (VEGF) family of ligands. VEGF ligands are overexpressed in a wide variety
      of solid tumors and therefore have inspired optimism that inhibition of the
      different axes of the VEGF pathway-alone or in combination-would represent
      powerful anti-angiogenic therapies for most cancer types. When considering
      treatments that target VEGF and its receptors, it is difficult to tease out the
      differential anti-angiogenic and anti-tumor effects of all combinations
      experimentally because tumor cells and vascular endothelial cells are engaged in
      a dynamic cross-talk that impacts key aspects of tumorigenesis, independent of
      angiogenesis. Here we develop a mathematical model that connects intracellular
      signaling responsible for both endothelial and tumor cell proliferation and death
      to population-level cancer growth and angiogenesis. We use this model to
      investigate the effect of bidirectional communication between endothelial cells
      and tumor cells on treatments targeting VEGF and its receptors both in vitro and
      in vivo. Our results underscore the fact that in vitro therapeutic outcomes do
      not always translate to the in vivo situation. For example, our model predicts
      that certain therapeutic combinations result in antagonism in vivo that is not
      observed in vitro. Mathematical modeling in this direction can shed light on the
      mechanisms behind experimental observations that manipulating VEGF and its
      receptors is successful in some cases but disappointing in others.

PMID- 28439754
TI  - Association Between Depression and Antiretroviral Therapy Use Among People Living
      with HIV: A Meta-analysis.
AB  - Depression is common among people living with HIV (PLHIV). Studies on the
      relationship between depression and use of antiretroviral therapy (ART) are
      inconclusive. A meta-analysis was conducted to summarize the relationship between
      depression and ART use among PLHIV. Ten electronic databases, conference
      abstracts, and dissertations were searched. A random effects meta-analysis was
      performed to pool the odds ratio estimates from eligible studies. Subgroup
      analyses and meta-regression were conducted for moderator analysis. Sensitivity
      analysis was performed to find influential studies. A funnel plot, the Egger
      test, and the trim and fill analysis were used to detect publication bias. The
      pooled sample size was 7375 PLHIV from nine eligible studies. The pooled
      prevalence of depression was 41% (95% confidence interval [CI] 29-53%). The
      pooled ART use rate was 52% (95% CI 37-67%). PLHIV with depression were 14% less
      likely (pooled odds ratio [OR] = 0.86; 95% CI 0.71-1.05) to use ART than those
      without depression. Subgroup analyses showed that depression was significantly
      associated with no ART use (pooled OR 0.84; 95% CI 0.71-0.99) among studies with
      a prospective study design (11 estimates from nine studies). Moderator analyses
      did not show any statistically significant effects. The publication bias analyses
      showed small study effects may not exist. Depression was associated with non-use
      of ART among PLHIV. Studies are needed to explore this association in other
      countries with varied populations, as most published studies have been conducted
      in the United States.

PMID- 28439753
TI  - Abating Mercury Exposure in Young Children Should Include Thimerosal-Free
      Vaccines.
AB  - : Pediatric immunization is essential to prevent, control and eradicate
      children's infectious diseases. Newborns and infants in less developed countries
      have a concentrated schedule of Thimerosal-containing vaccines (TCVs); pregnant
      mothers are also immunized with TCVs. Metabolic changes during early development
      are demonstrably an important risk factor for ethylmercury (EtHg) effects on
      neurodevelopment, while exposure to Thimerosal sensitizes susceptible individuals
      to life-long contact dermatitis. Concerns regarding toxicity of Hg have moved
      rich nations to withdraw it from medicines and, in particular, Thimerosal from
      pediatric vaccines; it has been more than 20 years since rich countries started
      using Thimerosal-free vaccines. TCVs and Thimerosal-free vaccines show dissimilar
      profiles of adverse effects. Thimerosal-free vaccines have shown a decrease in
      contact dermatitis, while TCVs showed a significant association with increased
      risk of tic disorders; in some circumstances, EtHg in combination with other
      neurotoxic substances negatively impacted neurobehavioral tests. In studies that
      explored vaccines and risk of tics, Thimerosal was a necessary factor. However,
      when the binary exposure to organic Hg forms (TCV-EtHg and fish-MeHg) was
      considered, effects on neurobehavioral tests were inconsistent. CONCLUSIONS: (a)
      The indiscriminate use of pediatric-TCVs in less developed countries carries an
      unjustifiable and excessive EtHg exposure with an unnecessary risk of
      neurotoxicity to the developing brain; (b) measurable benefits (of Thimerosal
      free) and measurable risks of tic disorders have been associated with the
      (Thimerosal-containing) type of vaccine;

PMID- 28439755
TI  - What do Key Stakeholders Think About HIV Self-Testing in Canada? Results from a
      Cross-Sectional Survey.
AB  - Human immunodeficiency virus (HIV) self-testing presents an empowering
      alternative to facility-based testing for reaching undiagnosed HIV infected
      individuals, but is not currently available in Canada. We surveyed stakeholders
      (clinical providers, public health professionals, researchers) engaged in HIV
      testing initiatives nationwide to identify the concerns, opportunities and
      challenges to implementing HIV self-testing in Canada. An online cross-sectional
      survey was disseminated by the Canadian Institutes of Health Research Centre for
      REACH 2.0 National HIV & sexually transmitted and blood borne infections working
      group to stakeholders nationwide, with a target sample size of 200. Quantitative
      and qualitative data were analyzed using a mixed-methods, respondent-informed
      approach, to inform subsequent HIV self-testing in a country where self-testing
      is not yet accessible. A total of 183 responses were received. A majority (70.7%)
      (128/181) felt that self-testing was a necessary investment to reach the
      undiagnosed. 64.6% (117/181) felt that self-tests should be made available to
      their clients and 71.5% (128/179) of respondents agreed that self-test
      instructions required improvements. However, 50% (90/180) felt that self-testing
      will pose an economic challenge to current HIV testing models. Regardless, 21%
      urged for timely action and availability of HIV self-tests. Thematic analyses
      reflected the following concerns: (a) need for affordable self-tests, (b) need
      for expedited, customized, and accessible linkages to counselling, (c) concern
      for patients to cope with positive self-test results, (d) accuracy of self-tests
      to detect acute HIV and (e) liability in the context of non-disclosure.
      Stakeholders agreed to the provision of an option of HIV self-testing to reach
      the undiagnosed individuals. Concerns regarding costs and accuracy of self-tests,
      expedited linkages to counselling, and integration of self-test within prevailing
      HIV testing models, will need to be addressed before their widespread
      implementation.

PMID- 28439756
TI  - Psychological Distress Among Methadone Maintenance Patients in Vietnamese
      Mountainous Areas.
AB  - We conducted a cross-sectional study in Tuyen Quang Province, a mountainous
      province in northern Vietnam, to examine rates of psychological distress among
      241 patients receiving methadone maintenance treatment (MMT). Using the Kessler
      psychological distress Scale, we found that approximately one-fourth (26.8%) of
      respondents suffered from mental health pathologies. Physical health problems,
      current drug use, and alcohol abuse were found to be associated with mental
      health problems among the participants. Our findings highlight the high
      prevalence of psychological distress among MMT patients in northern Vietnam, and
      the need to integrate mental and physical health care services, as well as
      behavioral health counseling, into currently existing MMT clinics in this region.

PMID- 28439757
TI  - When is Higher Level Cognitive Control Needed for Locomotor Tasks Among Patients
      with Parkinson's Disease?
AB  - Turning has been implicated as a complex task that requires both motor and
      cognitive resources. Accumulating evidence shows that patients with Parkinson's
      disease (PD) require more steps and more time to complete a turn, however, the
      role of the prefrontal cortex during turning is not clear. Forty nine patients
      with PD without freezing of gait (mean age 71.7 +/- 1.0 years; 67% men, disease
      duration 9.7 +/- 1.3 years) performed motor and cognitive tests. Prefrontal
      activation, specifically in Brodmann area 10 (BA10), during turning and usual
      walking was measured using functional near infrared spectroscopy (fNIRS). The
      patients with PD were further divided into two subgroups with high and low
      functional status based on limitations in community ambulation. General Linear
      Model analysis adjusted for age, gender, disease duration and turn duration was
      used to assess differences between tasks and subgroups of patients with PD. In
      addition, Pearson's correlation was performed to assess association between BA10
      activation and motor and cognitive scores. Activation in BA10 increased during
      walking (p < 0.001), while it decreased during turning (p = 0.006). A comparison
      between the two subgroups of patients with PD revealed that patients with
      relatively better ambulation decreased prefrontal activation during turning, as
      compared to patients with relatively worse ambulation (p < 0.001). These findings
      are the first to show that BA10 plays a different role during turning and walking
      and that ambulation status may alter BA10 activation during turning. Higher
      prefrontal activation during turning in the subgroup of patients with relatively
      worse ambulation may reflect a compensatory attempt at improving performance.

PMID- 28439759
TI  - ASNC and the world of nuclear cardiology.

PMID- 28439758
TI  - Molecular phylogeny of 21 tropical bamboo species reconstructed by integrating
      non-coding internal transcribed spacer (ITS1 and 2) sequences and their consensus
      secondary structure.
AB  - The unavailability of the reproductive structure and unpredictability of
      vegetative characters for the identification and phylogenetic study of bamboo
      prompted the application of molecular techniques for greater resolution and
      consensus. We first employed internal transcribed spacer (ITS1, 5.8S rRNA and
      ITS2) sequences to construct the phylogenetic tree of 21 tropical bamboo species.
      While the sequence alone could grossly reconstruct the traditional phylogeny
      amongst the 21-tropical species studied, some anomalies were encountered that
      prompted a further refinement of the phylogenetic analyses. Therefore, we
      integrated the secondary structure of the ITS sequences to derive individual
      sequence-structure matrix to gain more resolution on the phylogenetic
      reconstruction. The results showed that ITS sequence-structure is the reliable
      alternative to the conventional phenotypic method for the identification of
      bamboo species. The best-fit topology obtained by the sequence-structure based
      phylogeny over the sole sequence based one underscores closer clustering of all
      the studied Bambusa species (Sub-tribe Bambusinae), while Melocanna baccifera,
      which belongs to Sub-Tribe Melocanneae, disjointedly clustered as an out-group
      within the consensus phylogenetic tree. In this study, we demonstrated the
      dependability of the combined (ITS sequence+structure-based) approach over the
      only sequence-based analysis for phylogenetic relationship assessment of bamboo.

PMID- 28439760
TI  - Prognostic study of cardiac events in Japanese patients with chronic kidney
      disease using ECG-gated myocardial Perfusion imaging: Final 3-year report of the
      J-ACCESS 3 study.
AB  - BACKGROUND: Myocardial perfusion imaging (MPI) is considered useful for risk
      stratification among patients with chronic kidney disease (CKD), without renal
      deterioration by contrast media. METHODS AND RESULTS: The Japanese Assessment of
      Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS 3) is a
      multicenter, prospective cohort study investigating the ability of MPI to predict
      cardiac events in 529 CKD patients without a definitive coronary artery disease.
      All patients were assessed by stress and rest MPI with 99mTc-tetrofosmin and data
      were analyzed using a defect scoring method and QGS software. Major cardiac
      events were analyzed for 3 years after registration. The mean eGFR was 29.0 +/-
      12.8 (mL/minute/1.73 m2). The mean summed stress/rest/difference (SSS, SRS, SDS)
      scores were 1.9 +/- 3.8, 1.1 +/- 3.0, and 0.8 +/- 1.8, respectively. A total of
      60 cardiac events (three cardiac deaths, six sudden deaths, five nonfatal
      myocardial infarctions, 46 hospitalization cases for heart failure) occurred. The
      event-free survival rate was lower among patients with kidney dysfunction, higher
      SSS, and higher CRP values. Multivariate Cox regression analysis independently
      associated SSS >=8, eGFR <15 (mL/minute/1.73 m2), and CRP >=0.3 (mg/dL) with
      cardiac events. CONCLUSIONS: Together with eGFR and CRP, MPI can predict cardiac
      events in patients with CKD.

PMID- 28439761
TI  - Small Molecule Inhibitors in Chronic Lymphocytic Lymphoma and B Cell Non-Hodgkin
      Lymphoma.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the available
      literature for the use of small molecule inhibitors in chronic lymphocytic
      leukemia and B cell non-Hodgkin lymphoma. RECENT FINDINGS: Ibrutinib, idelalisib,
      and venetoclax are small molecule inhibitors that have revolutionized therapeutic
      options for patients with CLL, particularly for those with high-risk disease
      including 17p deletion. These drugs are increasingly finding application in a
      variety of subtypes of B cell NHL. Intolerance and resistance are concerns for
      select patients, highlighting the need for continual development of alternate
      therapies. The treatment armamentarium for CLL and NHL is vastly different than
      it was just a few years ago. Patients have a much wider range of non-chemotherapy
      treatment options, some of which produce durable responses and have long-term
      tolerability. Future research directions will likely focus on identifying the
      optimal sequences and combination strategies for these new targeted therapies.

PMID- 28439762
TI  - Sex Differences in Obesity and Mental Health.
AB  - PURPOSE OF REVIEW: The purposes of this study were to examine the relationships
      between obesity and a wide range of mental health issues and to identify where
      sex differences exist and may vary across disorders. RECENT FINDINGS: Research on
      sex differences in the relationship between obesity and psychiatric disorders is
      more abundant in some areas, such as depression and eating disorders, than
      others, such as anxiety, trauma, and substance use. However, for most of the
      disorders, their relationships with obesity and sex are complex and are usually
      moderated by additional variables. Thus, studies that find stronger relationships
      for women between depression and obesity cross-sectionally do not tell the whole
      story, as longitudinal studies suggest that this relationship may also be present
      among men, particularly when confounders are considered. For those with eating
      disorders, men and women with obesity are fairly equally affected, and weight and
      shape concerns may play a role in maintaining these behaviors for both sexes.
      Weight stigma, though, seems to have worse consequences for women than men with
      obesity. Sex differences exist in relation to the associations between mental
      health and obesity. However, these differences vary by disorder, with disorder
      specific moderators playing a role, such as age for depressive disorders,
      comorbid depression for anxiety disorders, and weight and shape concerns for
      eating disorders. More work is needed to understand if sex differences play a
      role in the relationship between obesity and anxiety, trauma, and substance use
      disorders.

PMID- 28439763
TI  - A phase II, multicenter, single-arm study of tri-weekly low-dose nanoparticle
      albumin-bound paclitaxel chemotherapy for patients with metastatic or recurrent
      breast cancer.
AB  - BACKGROUND: Nanoparticle albumin-bound (nab)-paclitaxel is a solvent-free
      formulation of paclitaxel that is bound to albumin and has demonstrated improved
      progression free survival in previous studies of breast cancer. However, it is
      difficult to treat Japanese patients with metastatic or recurrent breast cancer
      with the recommended dose of 260 mg/m2 of (nab)-paclitaxel for more than six
      cycles due to the occurrence of adverse events. To evaluate the treatment
      continuity and safety of low-dose nab-paclitaxel, we conducted a phase II study
      of nab-paclitaxel in patients with metastatic or recurrent breast cancer who had
      received up to one prior chemotherapy. PATIENTS AND METHODS: Treatment included
      low doses of 180 mg/m2 nab-paclitaxel that were administered on day 1 of each 3
      week cycle to 35 patients. The primary endpoint was the completion rate of six
      cycles of treatment. RESULTS: A total of 35 eligible patients were enrolled and
      received a median of eight (range 2-24) cycles of low-dose nab-paclitaxel
      therapy. The completion rate of six cycles of treatment was 66%. ORR and clinical
      benefit rate was 23 and 71%, respectively. Median PFS was 6.5 months and median
      OS was 44 months. Adverse events were relatively mild. Commonly observed grade
      3/4 adverse events were neutropenia (46%), leukopenia (9%), and hypertension
      (3%). No grade 3-4 peripheral sensory neuropathy occurred. CONCLUSION: Treatment
      with a low dose of nab-paclitaxel once every 3 weeks was tolerable and of
      acceptable safety and might be beneficial for patients with metastatic or
      recurrent breast cancer.

PMID- 28439764
TI  - Covariance Model Simulation Using Regular Vines.
AB  - We propose a new and flexible simulation method for non-normal data with user
      specified marginal distributions, covariance matrix and certain bivariate
      dependencies. The VITA (VIne To Anything) method is based on regular vines and
      generalizes the NORTA (NORmal To Anything) method. Fundamental theoretical
      properties of the VITA method are deduced. Two illustrations demonstrate the
      flexibility and usefulness of VITA in the context of structural equation models.
      R code for the implementation is provided.

PMID- 28439765
TI  - FeCl3-catalyzed [3+3] annulation between 3-oxirane-indolin-2-ones and nitrones to
      construct spiro[1,4,2-dioxazinan]oxindoles.
AB  - An efficient and mild procedure for the synthesis of spiro[1,4,2
      dioxazinan]oxindoles has been achieved in high yields by [Formula: see text]
      catalyzed annulation of 3-oxirane-indolin-2-ones and nitrones. This catalytic
      protocol demonstrates that the reaction could tolerate a variety of functional
      groups and provides convenient access to new structural motifs in good to
      excellent yields. Moreover, this method featured relatively short reaction time
      and easy operation.

PMID- 28439766
TI  - Enhanced butyric acid tolerance and production by Class I heat shock protein
      overproducing Clostridium tyrobutyricum ATCC 25755.
AB  - The response of Clostridium tyrobutyricum to butyric acid stress involves various
      stress-related genes, and therefore overexpression of stress-related genes can
      improve butyric acid tolerance and yield. Class I heat shock proteins (HSPs) play
      an important role in the process of protecting bacteria from sudden changes of
      extracellular stress by assisting protein folding correctly. The results of
      quantitative real-time PCR indicated that the Class I HSGs grpE, dnaK, dnaJ,
      groEL, groES, and htpG were significantly upregulated under butyric acid stress,
      especially the dnaK and groE operons. Overexpression of groESL and htpG could
      significantly improve the tolerance of C. tyrobutyricum to butyric acid, while
      overexpression of dnaK and dnaJ showed negative effects on butyric acid
      tolerance. Acid production was also significantly promoted by increased GroESL
      expression levels; the final butyric acid and acetic acid concentrations were
      28.2 and 38% higher for C. tyrobutyricum ATCC 25755/groESL than for the wild-type
      strain. In addition, when fed-batch fermentation was carried out using cell
      immobilization in a fibrous-bed bioreactor, the butyric acid yield produced by C.
      tyrobutyricum ATCC 25755/groESL reached 52.2 g/L, much higher than that for the
      control. The improved butyric acid yield is probably attributable to the high
      GroES and GroEL levels, which can stabilize the biosynthetic machinery of C.
      tyrobutyricum under extracellular butyric acid stress.

PMID- 28439767
TI  - A Bacillus subtilis strain as probiotic in poultry: selection based on in vitro
      functional properties and enzymatic potentialities.
AB  - We have proposed and validate an in vitro probiotic selection, based on enzymatic
      potentialities associated to well-established probiotic functional properties. A
      new Bacillus subtilis HB2 isolate, selected based on its high extracellular
      enzyme production, was chosen as a probiotic candidate for application as animal
      feed supplement. The HB2 strain showed an excellent acid and bile salts
      tolerance, a strong adhesion to chick enterocytes and produced antimicrobials
      against pathogens. An in vivo trial in poultry farming was conducted to evaluate
      the HB2 probiotic performance. After 35 days, HB2 achieved the higher growth
      performance than the control groups. The mortality and the feed conversion ratio
      were significantly decreased. Finally, the HB2 treated group showed wet litter
      and less severe ammonia odor in the atmosphere. Our study provides new insights
      into the importance of enzymatic potentialities, associated with the common
      functional properties, as a novel approach for probiotic selection.

PMID- 28439768
TI  - Discrimination of wine lactic acid bacteria by Raman spectroscopy.
AB  - Species of Lactobacillus, Pediococcus, Oenococcus, and Leuconostoc play an
      important role in winemaking, as either inoculants or contaminants. The metabolic
      products of these lactic acid bacteria have considerable effects on the flavor,
      aroma, and texture of a wine. However, analysis of a wine's microflora,
      especially the bacteria, is rarely done unless spoilage becomes evident, and
      identification at the species or strain level is uncommon as the methods required
      are technically difficult and expensive. In this work, we used Raman spectral
      fingerprints to discriminate 19 strains of Lactobacillus, Pediococcus, and
      Oenococcus. Species of Lactobacillus and Pediococcus and strains of O. oeni and
      P. damnosus were classified with high sensitivity: 86-90 and 84-85%,
      respectively. Our results demonstrate that a simple, inexpensive method utilizing
      Raman spectroscopy can be used to accurately identify lactic acid bacteria
      isolated from wine.

PMID- 28439769
TI  - Perceived Neighborhood Safety Is Associated with Poor Sleep Health among Gay,
      Bisexual, and Other Men Who Have Sex with Men in Paris, France.
AB  - Recent studies have examined sleep health among men who have sex with men (MSM),
      but no studies have examined associations of neighborhood characteristics and
      sleep health among this population. The purpose of this study was to examine
      associations between perceived neighborhood safety and sleep health among a
      sample of MSM in Paris, France. We placed broadcast advertisements on a popular
      smartphone application for MSM in October 2016 to recruit users in the Paris
      (France) metropolitan area (n = 580). Users were directed to complete a web-based
      survey, including previously used items measuring perceptions of neighborhood
      safety, validated measures of sleep health, and socio-demographics. Modified
      Poisson models were used to estimate risk ratios (RRs) and 95% confidence
      intervals (CI) for the associations between perceived neighborhood safety and the
      following outcomes: (1) poor sleep quality, (2) short sleep duration, and (3)
      self-reported sleep problems. Poor sleep health was common in our sample; e.g.,
      30.1% reported poor sleep quality and 44.7% reported problems falling asleep. In
      multivariate regression models, perceived neighborhood safety was associated with
      poor sleep quality, short sleep duration, and having sleep problems. For example,
      reporting living in a neighborhood perceived as unsafe during the daytime (vs.
      safe) was associated with poor sleep quality (aRR, 1.60; 95% CI, 1.01, 2.52),
      short sleep duration (aRR, 1.92; 95% CI, 1.26, 2.94), problems falling asleep
      (aRR, 1.57; 95% CI, 1.17, 2.11), and problems staying awake in the daytime (aRR,
      2.16; 95% CI, 1.05, 4.43). Interventions to increase neighborhood safety may
      improve sleep health among MSM.

PMID- 28439770
TI  - Gastric Preconditioning in Advance of Esophageal Resection-Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Anastomotic leakage is one of the most severe complications following
      esophageal resection. Among other strategies, gastric ischemic preconditioning
      has been proposed to improve anastomotic integrity. The aim of this systematic
      review is to investigate whether gastric preconditioning has influence on peri-
      or postoperative outcomes after esophageal resection. METHODS: A systematic
      literature search was performed to identify studies comparing gastric
      preconditioning with non-preconditioned patients for any indication of esophageal
      resection. Random-effects meta-analyses were conducted for main outcomes.
      RESULTS: Gastric preconditioning did not reduce anastomotic leakages (OR 0.76;
      95%-CI 0.51 to 1.13; p = 0.18), anastomotic strictures (OR 1.10; 95%-CI 0.58 to
      2.10; p = 0.76;), major complications (OR 1.14; 95%-CI 0.60 to 2.14; p = 0.69),
      or in-hospital mortality (OR 0.62; 95%-CI 0.28 to 1.40; p = 0.25). However,
      preconditioning reduced the rate of severe leaks requiring reoperation (OR 0.20;
      95%-CI 0.08 to 0.53; p = 0.001). Increasing the period between preconditioning
      and esophageal resection over 2 weeks did not reduce anastomotic leakage compared
      to shorter waiting times (OR 0.65; 95%-CI 0.38 to 1.13; p = 0.13). CONCLUSION:
      With current evidence, gastric preconditioning does not seem to reduce overall
      rates of anastomotic leakage after esophageal resection but seems to reduce
      severity of leakages.

PMID- 28439771
TI  - Neurobiological Programming of Early Life Stress: Functional Development of
      Amygdala-Prefrontal Circuitry and Vulnerability for Stress-Related
      Psychopathology.
AB  - Early adverse experiences are associated with heighted vulnerability for stress
      related psychopathology across the lifespan. While extensive work has
      investigated the effects of early adversity on neurobiology in adulthood,
      developmental approaches can provide further insight on the neurobiological
      mechanisms that link early experiences and long-term mental health outcomes. In
      the current review, we discuss the role of emotion regulation circuitry
      implicated in stress-related psychopathology from a developmental and
      transdiagnostic perspective. We highlight converging evidence suggesting that
      multiple forms of early adverse experiences impact the functional development of
      amygdala-prefrontal circuitry. Next, we discuss how adversity-induced alterations
      in amygdala-prefrontal development are associated with symptoms of emotion
      dysregulation and psychopathology. Additionally, we discuss potential mechanisms
      through which protective factors may buffer the effects of early adversity on
      amygdala-prefrontal development to confer more adaptive long-term outcomes.
      Finally, we consider limitations of the existing literature and make suggestions
      for future longitudinal and translational research that can better elucidate the
      mechanisms linking early adversity, neurobiology, and emotional phenotypes.
      Together, these findings may provide further insight into the neuro-developmental
      mechanisms underlying the emergence of adversity-related emotional disorders and
      facilitate the development of targeted interventions that can ameliorate risk for
      psychopathology in youth exposed to early life stress.

PMID- 28439772
TI  - Neuromonitoring in endoscopic and robotic thyroidectomy.
AB  - Intraoperative neuromonitoring (IONM) has proven effective for intraoperative
      verification of RLN function in the conventional thyroid surgery. However, no
      studies have performed a systematic evidence-based assessment of this novel
      health technology in endoscopic and robotic thyroidectomy. Evidence-based
      criteria were used in a systematic review of relevant literature for years 2000
      2015. Four electronic databases (CENTRAL, MEDLINE, Cochrane and EMBASE) were used
      to retrieve relevant reports published from January 1, 2000 to September 1, 2016.
      The search terms included "endoscopic thyroidectomy", "robotic thyroidectomy",
      "IONM", "continuous IONM (CIONM)", "neural monitoring", "recurrent laryngeal
      nerve monitoring", and "superior laryngeal monitoring". The following data were
      retrieved from eligible studies of patients undergoing endoscopic or robotic
      thyroidectomy: objective of study, design and setting of study, population,
      intervention examined, quality of data, follow-up and dropout rate, risk of bias,
      and outcomes assessed. Of 160 studies retrieved, only 9 (5%) studies used IONM.
      Eight studies reported 522 nerve at risk (NAR) with IONM. Only three were
      prospective randomized studies. Reports of IONM endoscopic and robotic procedures
      included their use for re-surgery and use in both benign and malignant cases.
      None of the IONM endoscopic procedures involved bilateral palsy. Two studies
      reported the use of a staged strategy. The rates of recurrent laryngeal palsy
      were 0-3.6% for transient and 0-0.4% for permanent. Only 30% of the studies
      performed vagus nerve stimulation, and only 25% performed superior laryngeal
      nerve monitoring. In addition to the use of IONM as an assistive technology for
      navigating the anatomy in challenging procedures such as endoscopic and robotic
      thyroidectomy, IONM has potential use as a routine adjunct to the conventional
      video-assisted nerve identification in thyroidectomy.

PMID- 28439773
TI  - Parsonage-Turner syndrome due to autochthonous acute genotype 3f hepatitis E
      virus infection in a nonimmunocompromised 55-year-old patient.
AB  - Hepatitis E virus (HEV) infection is an emerging autochthonous disease in
      industrialized countries. Extra-hepatic manifestations, in particular neurologic
      manifestations, have been reported in HEV infection. Only a few cases of
      hepatitis E-associated Parsonage-Turner syndrome have been reported, and HEV
      genotypes were rarely determined. Here, we report the case of a Parsonage-Turner
      syndrome associated with an acute autochthonous HEV infection in a 55-year-old
      immunocompetent patient. HEV genomic RNA was detected in serum and cerebrospinal
      fluid samples (CSF), and molecular phylogenetic analysis of HEV was performed.
      The interest of this case lies in its detailed description notably the molecular
      analysis of HEV RNA isolated from serum and CSF. HEV infection should be
      considered in diagnostic investigations of neurologic manifestations associated
      with liver function perturbations.

PMID- 28439774
TI  - Albumin-Induced Neuroprotection in Focal Cerebral Ischemia in the ALIAS Trial:
      Does Severity, Mechanism, and Time of Infusion Matter?
AB  - OBJECTIVE: To determine whether there is any differential benefit of albumin
      administration within 2 h of onset of ischemia and in settings (severe ischemia
      with reperfusion in cardioembolic strokes with National Institutes of Health
      Stroke Scale [NIHSS] >=15), most representative of experimental models of
      cerebral ischemia in which albumin was effective in reducing neurological injury.
      BACKGROUND: High-dose intravenous (IV) albumin treatment for acute ischemic
      stroke (ALIAS) trial did not show overall clinical benefit in ischemic stroke
      patients in contrast to preclinical studies; however, models of preclinical
      studies were not completely followed. METHODS: A total of 1275 patients combined
      from ALIAS trials I and II were included in our analysis. We analyzed preclinical
      studies and selected patients with large ischemic stroke (NIHSS >=15) related to
      cardioembolic etiology (n = 189). Outcomes were then studied including time from
      onset to IV albumin administration. RESULTS: The odds of excellent outcome (mRS 0
      1) at 3 months was not different with high-dose IV albumin infusion (n = 100)
      compared with placebo (n = 89) ((odds ratio [OR]) 1.632 [0.719-3.708], p value
      0.2419). When we further classified these subjects according to time of IV
      albumin administration, we observed significantly higher odds of excellent
      outcome at 3 months when patients received IV albumin within 2 h, OR 9.369 (CI
      1.040-84.405), p value 0.0461, after adjusting for age, gender, baseline NIHSS
      score, and any therapeutic procedure. CONCLUSION: A trend for benefit is noted in
      ischemic stroke patients with large cardioembolic stroke (NIHSS >=15) when high
      dose albumin was initiated within 2 h, suggesting that certain ischemic stroke
      subgroups of patients most representative of preclinical settings may benefit
      from such a treatment. Additional clinical trials maybe needed to stratify
      subjects and treatment assignments according to NIHSS severity and timely
      randomization to evaluate this concept further.

PMID- 28439775
TI  - The prognostic significance of 13q deletions of different sizes in patients with
      B-cell chronic lymphoproliferative disorders: a retrospective study.
AB  - Patients with chronic lymphocytic leukemia (CLL) with 13q deletion as the sole
      cytogenetic abnormality usually have a favorable outcome, but the frequency of
      the 13q14 deletion and its impact on the outcome of other B-cell chronic
      lymphoproliferative disorders (BCLPDs) remain unclear. To further characterize
      this aberration, we investigated the prognostic significance of 13q deletion in
      541 patients with BCLPDs. We performed fluorescence in situ hybridization (FISH)
      studies with 13q locus-specific LSI-D13S25 and LSI-RB1 probes. 52.1% of the
      patients with CLL harbored 13q deletion, which was significantly higher than that
      of other BCLPDs (p < 0.001). The size of 13q deletion was heterogeneous in both
      CLL and other BCLPDs. However, the distribution of cases with different deletion
      sizes showed no significant difference between the two groups. Whereas 13q
      deletion was a favorable prognostic factor in CLL, a large deletion of 13q was
      associated with poor prognosis in terms of time to first therapy (p = 0.020),
      progression-free survival (p = 0.05) and overall survival (p = 0.002) in BCLPD
      cases other than CLL. In conclusion, the deletion of 13q varied in size both in
      CLL and in other BCLPDs and adversely influenced the prognosis of patients with
      other BCLPDs.

PMID- 28439776
TI  - Preoperative grading of supratentorial nonenhancing gliomas by high b-value
      diffusion-weighted 3 T magnetic resonance imaging.
AB  - The purpose of this study was to determine the difference in discrimination
      between high- and low-grade supratentorial nonenhancing gliomas (HGGs and LGGs,
      respectively) when using apparent diffusion coefficient (ADC) values with high or
      standard b-value. Thirty-nine patients underwent conventional magnetic resonance
      imaging and diffusion-weighted imaging (DWI) with standard and high b-values (b =
      1000 and 3000 s/mm2, respectively). Minimum, maximum, and mean ADC values
      (ADCMIN, ADCMAX, and ADCMEAN, respectively) were measured from ADC maps with both
      b-values. Receiver operating curve analysis was used to determine the cutoff ADC
      values for distinguishing between nonenhancing HGGs and LGGs. ADCMIN, ADCMAX, and
      ADCMEAN values for the nonenhancing HGGs were lower than those for LGGs. These
      differences were much larger when a high b-value was used (all P < 0.0001) than
      when a standard b-value was used (P = 0.0001, <0.0001, and <0.0001,
      respectively). Discriminant analysis indicated that the greatest likelihood for
      discriminating HGGs and LGGs when ADCMEAN was obtained with a high b-value, with
      cutoff value of 0.814 * 10-3 mm2/s. ADC values obtained with a high b-value can
      be useful for grading and surgical management of nonenhancing HGGs and LGGs. The
      lowest degree of overlap was obtained when ADCMEAN was determined with a b-value
      of 3000 s/mm2.

PMID- 28439777
TI  - Survival trends of oligodendroglial tumor patients and associated clinical
      practice patterns: a SEER-based analysis.
AB  - There is limited information on the management strategies and survival trends for
      oligodendroglioma patients. Here we used the Surveillance, Epidemiology and End
      Results (SEER, 1999-2012) database to analyze the historical trends of
      oligodendroglioma patient survival and correlate these trends to evolving
      clinical practice of radiation therapy (RT) use and surgical practice of gross
      total resection (GTR). We identified 2689 World Health Organization (WHO) grade
      II oligodendroglioma (abbreviated as O2) and 1191 WHO grade III oligodendroglioma
      (abbreviated as O3). Time-trend analyses were performed for overall survival,
      radiation treatment (RT) use, and extent of surgical resection (EOR). In
      multivariable Cox models that accounted for age, race, sex, tumor size, tumor
      location, EOR, and RT status, the hazard of dying from O3 has significantly
      decreased over the study period (p  <  0.01), while the hazard of dying from O2
      has remained largely unchanged. A search of the published literature revealed
      articles reporting results largely supportive of these observations. The pattern
      of surgical practice and RT for O3 patients remained unchanged throughout the
      study period, suggesting that the survival improvement may be related to evolving
      patterns of medical management. Results from the SEER database indicate
      significant gains have been made in survival for O3 patients between 1999 and
      2012. Such gains were not observed for O2 patients during this study period.

PMID- 28439779
TI  - Searching for an Internal Representation of Stimulus Kinematics in the Response
      of Ventral Paraflocculus Purkinje Cells.
AB  - Motor control theories propose that the central nervous system builds internal
      representations of the motion of both our body and external objects. These
      representations, called forward models, are essential for accurate motor control.
      For instance, to produce a precise reaching movement to catch a flying ball, the
      central nervous system must build predictions of the current and future states of
      both the arm and the ball. Accumulating evidence suggests that the cerebellar
      cortex contains a forward model of an individual's body movement. However, little
      evidence is yet available to suggest that it also contains a forward model of the
      movement of external objects. We investigated whether Purkinje cell simple spike
      responses in an oculomotor region of the cerebellar cortex called the ventral
      paraflocculus contained information related to the kinematics of behaviorally
      relevant visual stimuli. We used a visuomotor task that obliges animals to track
      moving targets while keeping their eyes fixated on a stationary target to
      separate signals related to visual tracking from signals related to eye movement.
      We found that ventral paraflocculus Purkinje cells do not contain information
      related to the kinematics of behaviorally relevant visual stimuli; they only
      contain information related to eye movements. Our data stand in contrast with
      data obtained from cerebellar Crus I, wherein Purkinje cell discharge contains
      information related to moving visual stimuli. Together, these findings suggest
      specialization in the cerebellar cortex, with some areas participating in the
      computation of our movement kinematics and others computing the kinematics of
      behaviorally relevant stimuli.

PMID- 28439778
TI  - Dabigatran etexilate: appropriate use in patients with chronic kidney disease and
      in the elderly patients.
AB  - Dabigatran etexilate (DE) is a direct thrombin inhibitor, which has been approved
      for the treatment of non-valvular atrial fibrillation (AF), and for the
      prevention and treatment of venous thromboembolism (VTE). Despite large
      randomized clinical trials and independent observational studies providing robust
      data concerning DE safety and efficacy, some physicians still perceive mild-to
      moderate renal impairment and old age as a relative contraindication to its use.
      In this article, we review the available scientific evidence supporting the use
      of DE in these clinical situations. Patients with AF and chronic kidney disease
      (CKD) are per se at high risk of stroke, bleeding and mortality. Although there
      is evidence of clinical benefit of anticoagulation in these patients,
      anticoagulant therapy requires caution and demands careful clinical monitoring,
      regardless of the drug used. In patients with no contraindication to its use, the
      clinical benefit of DE versus warfarin is independent of renal function. The
      elderly with AF are frequently undertreated because of the perception of high
      bleeding risk and limited clinical benefit. However, the clinical benefit of
      anticoagulation is independent of patient age, and age per se should not
      represent a contraindication to anticoagulation. DE has been extensively studied
      in the elderly, both in randomized clinical trials and in observational studies:
      DE 150 mg BID should not be used in patients 80 years of age or older, while DE
      110 mg BID is as safe as warfarin. Intracranial haemorrhages reduction by DE
      compared with warfarin is preserved in the elderly. Therefore, mild and moderate
      CKD and being elderly should not deter physicians from prescribing DE.
      Furthermore, the availability of a specific antidote is expected to improve the
      safety of the use of DE in clinical practice.

PMID- 28439780
TI  - Angelica keiskei, an emerging medicinal herb with various bioactive constituents
      and biological activities.
AB  - Angelica keiskei (Miq.) Koidz. (Umbelliferae) has traditionally been used to
      treat dysuria, dyschezia, and dysgalactia as well as to restore vitality.
      Recently, the aerial parts of A. keiskei have been consumed as a health food.
      Various flavonoids, coumarins, phenolics, acetylenes, sesquiterpene, diterpene,
      and triterpenes were identified as the constituents of A. keiskei. The crude
      extracts and pure constituents were proven to inhibit tumor growth and ameliorate
      inflammation, obesity, diabetics, hypertension, and ulcer. The extract also
      showed anti-thrombotic, anti-oxidative, anti-hyperlipidemic, anti-viral, and anti
      bacterial activities. This valuable herb needs to be further studied and
      developed not only to treat these human diseases but also to improve human
      health. Currently A. keiskei is commercialized as a health food and additives in
      health drinks. This article presents a comprehensive review of A. keiskei and its
      potential place in the improvement of human health.

PMID- 28439781
TI  - Batrachochytrium dendrobatidis and the Decline and Survival of the Relict Leopard
      Frog.
AB  - Epizootic disease caused by the fungal pathogen Batrachochytrium dendrobatidis
      (Bd) is a major driver of amphibian declines, yet many amphibians declined before
      the pathogen was described. The Relict Leopard Frog, Rana onca (=Lithobates
      onca), was nearly extinct, with the exception of populations within a few
      geothermal springs. Growth of Bd, however, is limited by high water temperature,
      and geothermal springs may have provided refuge during outbreaks of
      chytridiomycosis. We conducted field surveys and laboratory experiments to assess
      the susceptibility of R. onca to Bd. In the field, we found Bd at one of the two
      areas where remnant populations of R. onca still occur, but not in the other. In
      the laboratory, we infected juvenile frogs from these two areas with two
      hypervirulent Bd isolates associated with declines in other ranid species. In our
      experiments, these Bd isolates did not affect survivorship of R. onca and most
      infections (64%) were cleared by the end of the experiments. We propose that R.
      onca either has inherent resistance to Bd or has recently evolved such
      resistance. These results may be important for conservation efforts aimed at
      establishing new populations of R. onca across a landscape where Bd exists.
      Resistance, however, varies among life stages, and we also did not assess Bd from
      the local environment. We caution that the resistance we observed for young frogs
      under laboratory conditions may not translate to the situation for R. onca in the
      wild.

PMID- 28439782
TI  - Continuous ventilation using a modified laparoscopic port and laryngeal mask
      airway during flexible bronchoscopic intubation.

PMID- 28439783
TI  - Dourine: a neglected disease of equids.
AB  - Dourine is a venereal transmitted trypanosomosis causing a major health problem
      threatening equines worldwide. The origin and identification of Trypanosoma
      equiperdum within the subgenus Trypanozoon is still a subject of debate. Unlike
      other trypanosomal infections, dourine is transmitted almost exclusively by
      coitus. Diagnosis of dourine has continued to be a challenge, due to limited
      knowledge about the parasite and host-parasite interaction following infection.
      The pathological lesions caused by the diseases are poorly described and are
      observed mainly in the reproductive organs, in the nervous system, and on the
      skin. Dourine has been neglected by research and current knowledge on the
      disease, and the parasite is very deficient despite its considerably high burden.
      This paper looks in to the challenges in identification of T. equiperdum and
      diagnosis techniques with the aim to update our current knowledge of the disease.

PMID- 28439784
TI  - Practical calculation method to estimate the absolute boron concentration in
      tissues using 18F-FBPA PET.
AB  - PURPOSE: The purpose of this study was to establish a practical method to
      estimate the absolute boron concentrations in the tissues based on the
      standardized uptake values (SUVs) after administration of 4-borono-phenylalanine
      (BPA) using 4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) PET. METHODS: Rat
      xenograft models of C6 glioma (n = 7, body weight 241 +/- 28.0 g) were used for
      the study. PET was performed 60 min after intravenous injection of 18F-FBPA (30.5
      +/- 0.7 MBq). After the PET scanning, BPA-fructose (167.3 +/- 18.65 mg/kg) was
      administered by slow intravenous injection to the same subjects. The rats were
      killed 60 min after the BPA injection and tissue samples were collected from the
      major organs and tumors. The absolute boron concentrations (unit: ppm) in the
      samples were measured by inductively coupled plasma optical emission spectrometry
      (ICP-OES). The boron concentrations in the tissues/tumors were also estimated
      from the 18F-FBPA PET images using the following formula: estimated absolute
      boron concentration (ppm) = 0.0478 * [BPA dose (mg/kg)] * SUV. The measured
      absolute boron concentrations (mBC) by ICP-OES and the estimated boron
      concentrations (eBC) from the PET images were compared. RESULTS: The percent
      difference between the mBC and eBC calculated based on the SUVmax was -5.2 +/-
      21.1% for the blood, -9.4 +/- 22.3% for the brain, 1.6 +/- 21.3% for the liver, 
      14.3 +/- 16.8% for the spleen, -9.5 +/- 27.5% for the pancreas, and 3.4 +/- 43.2%
      for the tumor. Relatively large underestimation was observed for the lung (-48.4
      +/- 16.2%), small intestine (-37.8 +/- 19.3%) and large intestine (-33.9 +/-
      11.0%), due to the partial volume effect arising from the air or feces contained
      in these organs. In contrast, relatively large overestimation was observed for
      the kidney (34.3 +/- 29.3%), due to the influence of the high uptake in urine.
      CONCLUSIONS: The absolute boron concentrations in tissues/tumors can be estimated
      from the SUVs on 18F-FBPA PET using a practical formula. Caution must be
      exercised in interpreting the estimated boron concentrations in the lung, small
      intestine and large intestine, to prevent the adverse effects of overexposure,
      which could occur due to underestimation by partial volume effect using PET.

PMID- 28439785
TI  - Influence of Environmental Conditions on Norovirus Presence in Mussels Harvested
      in Montenegro.
AB  - This study comprises the first systematic survey of the occurrence of Norovirus
      in Mediterranean mussels from harvesting areas in Montenegro coast of Adriatic
      Sea. Mussels may accumulate contaminants of public health concern, including
      pathogenic bacteria and viruses. Microbiological monitoring of harvesting areas
      is based on count of Escherichia coli in bivalve molluscs in the European Union.
      It is assumed that E. coli does not reflect contamination with enteric viruses. A
      structured field study was undertaken at six locations in Bay of Kotor,
      Montenegro, in order to investigate plausible influence of environmental factors
      on the variability of E. coli and norovirus (NoV). From July 2015 to July 2016, a
      total of 72 samples of mussels were collected in coastal harvesting areas of the
      Montenegro. The samples were screened for NoV of genogroups GI and GII using
      reverse transcription-qPCR (RT-qPCR). There were 43% NoV positive samples with
      higher presence of genogroup GII (74.2%). With regard to influence of
      environmental conditions on Norovirus presence, we have proved seasonal pattern
      of virus occurrence i.e., the largest number of positive samples was noticed
      during winter, while other physico-chemical factors were not of great
      significance. It was found that count of E. coli did not correlate with Norovirus
      prevalence. From the aspect of food safety, an upgrade of monitoring plans could
      lead to obtaining safer products.

PMID- 28439786
TI  - A panel of 130 autosomal single-nucleotide polymorphisms for ancestry assignment
      in five Asian populations and in Caucasians.
AB  - Ancestry informative single-nucleotide polymorphism (AISNP) panels for
      differentiating between East and Southeast Asian populations are scarce. This
      study aimed to identify AISNPs for ancestry assignment of five East and Southeast
      Asian populations, and Caucasians. We analyzed 145 autosomal SNPs of the 627 DNA
      samples from individuals of six populations (234 Taiwanese Han, 91 Filipinos, 79
      Indonesians, 60 Thais, 71 Vietnamese, and 92 Caucasians) using arrays. The
      multiple logistic regression model and a multi-tier approach were used for
      ancestry classification. We observed that 130 AISNPs were effective for
      classifying the ethnic origins with fair accuracy. Among the 130 AISNPs, 122 were
      useful for stratification between these five Asian populations and 64 were
      effective for differentiating between Caucasians and these Asian populations. For
      differentiation between Caucasians and Asians, an accuracy rate of 100% was
      achieved in these 627 subjects with 50 optimal AISNPs among the 64 effective
      SNPs. For classification of the five Asian populations, the accuracy rates of
      ancestry inference using 20 to 57 SNPs for each of the two Asian populations
      ranged from 74.1% to 100%. Another 14 degraded DNA samples with incomplete
      profiling were analyzed, and the ancestry of 12 (85.7%) of those subjects was
      accurately assigned. We developed a 130-AISNP panel for ethnic origin
      differentiation between the five East and Southeast Asian populations and
      Caucasians. This AISNP set may be helpful for individual ancestral assignment of
      these populations in forensic casework.

PMID- 28439787
TI  - Social Withdrawal Among Individuals Receiving Psychiatric Care: Derivation of a
      Scale Using Routine Clinical Assessment Data to Support Screening and Outcome
      Measurement.
AB  - Social withdrawal is a symptom experienced by individuals with an array of mental
      health conditions, particularly those with schizophrenia and mood disorders.
      Assessments of social withdrawal are often lengthy and may not be routinely
      integrated within the comprehensive clinical assessment of the individual. This
      study utilized item response and classical test theory methods to derive a Social
      Withdrawal Scale (SWS) using items embedded within a routine clinical assessment,
      the RAI-Mental Health (RAI-MH). Using data from 60,571 inpatients in Ontario,
      Canada, a common factor analysis identified seven items from the RAI-MH that
      measure social withdrawal. A graded response model found that six items had
      acceptable discrimination parameters: lack of motivation, reduced interaction,
      decreased energy, flat affect, anhedonia, and loss of interest. Summing these
      items, the SWS was found to have strong internal consistency (Cronbach's alpha =
      0.82) and showed a medium to large effect size (d = 0.77) from admission to
      discharge. Fewer individuals with high SWS scores participated in social activity
      or reported having a confidant compared to those with lower scores. Since the RAI
      MH is available across clinical subgroups in several jurisdictions, the SWS is a
      useful tool for screening, clinical decision support, and evaluation.

PMID- 28439788
TI  - Therapist and Organizational Factors Associated with Participation in Evidence
      Based Practice Initiatives in a Large Urban Publicly-Funded Mental Health System.

PMID- 28439789
TI  - Implementation of Electronic Health Records Among Community Mental Health
      Agencies.

PMID- 28439791
TI  - Task-irrelevant distractors in the delay period interfere selectively with visual
      short-term memory for spatial locations.
AB  - Visual short-term memory (VSTM) enables the representation of information in a
      readily accessible state. VSTM is typically conceptualized as a form of "active"
      storage that is resistant to interference or disruption, yet several recent
      studies have shown that under some circumstances task-irrelevant distractors may
      indeed disrupt performance. Here, we investigated how task-irrelevant visual
      distractors affected VSTM by asking whether distractors induce a general loss of
      remembered information or selectively interfere with memory representations. In a
      VSTM task, participants recalled the spatial location of a target visual stimulus
      after a delay in which distractors were presented on 75% of trials. Notably, the
      distractor's eccentricity always matched the eccentricity of the target, while in
      the critical conditions the distractor's angular position was shifted either
      clockwise or counterclockwise relative to the target. We then computed estimates
      of recall error for both eccentricity and polar angle. A general interference
      model would predict an effect of distractors on both polar angle and eccentricity
      errors, while a selective interference model would predict effects of distractors
      on angle but not on eccentricity errors. Results showed that for stimulus angle
      there was an increase in the magnitude and variability of recall errors. However,
      distractors had no effect on estimates of stimulus eccentricity. Our results
      suggest that distractors selectively interfere with VSTM for spatial locations.

PMID- 28439790
TI  - Evaluating Fidelity to a Modified NIATx Process Improvement Strategy for
      Improving HIV Services in Correctional Facilities.
AB  - In a study aimed at improving the quality of HIV services for inmates, an
      organizational process improvement strategy using change teams was tested in 14
      correctional facilities in 8 US states and Puerto Rico. Data to examine fidelity
      to the process improvement strategy consisted of quantitative ratings of the
      structural and process components of the strategy and qualitative notes that
      explicate challenges in maintaining fidelity to the strategy. Fidelity challenges
      included (1) lack of communication and leadership within change teams, (2)
      instability in team membership, and (3) issues with data utilization in decision
      making to implement improvements to services delivery.

PMID- 28439792
TI  - Short-term and long-term attentional biases to frequently encountered target
      features.
AB  - It has long been known that frequently occurring targets are attended better than
      infrequent ones in visual search. But does this frequency-based attentional
      prioritization reflect momentary or durable changes in attention? Here we
      observed both short-term and long-term attentional biases for visual features as
      a function of different types of statistical associations between the targets,
      distractors, and features. Participants searched for a target, a line oriented
      horizontally or vertically among diagonal distractors, and reported its length.
      In one set of experiments we manipulated the target's color probability: Targets
      were more often in Color 1 than in Color 2. The distractors were in other colors.
      Participants found Color 1 targets more quickly than Color 2 targets, but this
      preference disappeared immediately when the target's color became random in the
      subsequent testing phase. In the other set of experiments, we manipulated the
      diagnostic values of the two colors: Color 1 was more often a target than a
      distractor; Color 2 was more often a distractor than a target. Participants found
      Color 1 targets more quickly than Color 2 targets. Importantly, and in contrast
      to the first set of experiments, the featural preference was sustained in the
      testing phase. These results suggest that short-term and long-term attentional
      biases are products of different statistical information. Finding a target
      momentarily activates its features, inducing short-term repetition priming. Long
      term changes in attention, on the other hand, may rely on learning diagnostic
      features of the targets.

PMID- 28439793
TI  - Mixed signals: The effect of conflicting reward- and goal-driven biases on
      selective attention.
AB  - Attentional selection depends on the interaction between exogenous (stimulus
      driven), endogenous (goal-driven), and selection history (experience-driven)
      factors. While endogenous and exogenous biases have been widely investigated,
      less is known about their interplay with value-driven attention. The present
      study investigated the interaction between reward-history and goal-driven biases
      on perceptual sensitivity (d') and response time (RT) in a modified cueing
      paradigm presenting two coloured cues, followed by sinusoidal gratings.
      Participants responded to the orientation of one of these gratings. In Experiment
      1, one cue signalled reward availability but was otherwise task irrelevant. In
      Experiment 2, the same cue signalled reward, and indicated the target's most
      likely location at the opposite side of the display. This design introduced a
      conflict between reward-driven biases attracting attention and goal-driven biases
      directing it away. Attentional effects were examined comparing trials in which
      cue and target appeared at the same versus opposite locations. Two interstimulus
      interval (ISI) levels were used to probe the time course of attentional effects.
      Experiment 1 showed performance benefits at the location of the reward-signalling
      cue and costs at the opposite for both ISIs, indicating value-driven capture.
      Experiment 2 showed performance benefits only for the long ISI when the target
      was at the opposite to the reward-associated cue. At the short ISI, only
      performance costs were observed. These results reveal the time course of these
      biases, indicating that reward-driven effects influence attention early but can
      be overcome later by goal-driven control. This suggests that reward-driven biases
      are integrated as attentional priorities, just as exogenous and endogenous
      factors.

PMID- 28439794
TI  - The Effectiveness of Voriconazole in Therapy of Candida glabrata's Biofilms Oral
      Infections and Its Influence on the Matrix Composition and Gene Expression.
AB  - Candida glabrata is one of most prevalent yeast in fungal infections, especially
      in immunocompromised patients. Its azole resistance results in a low therapeutic
      response, particularly when associated with biofilms. The main goal of this work
      was to study the effectiveness of voriconazole (Vcz) against C. glabrata biofilms
      oral pathologies, as esophageal or oropharyngeal candidiasis. Antifungal
      susceptibilities were determined in pre-formed 24-h-biofilms and ERG genes
      expression was determined by qRT-PCR. Protein quantification was performed using
      BCA(r) Kit, carbohydrate was estimated according to the Dubois assay and beta-1,3
      glucans concentration were determined using Glucatell(r) kit. Finally,
      ergosterol, Vcz, and fluconazole (Flu) concentrations within the biofilm matrices
      were determined by RP-HPLC. Results showed that C. glabrata biofilms were more
      susceptible to Vcz than to Flu and that ERG genes expression evidenced an
      overexpression of the three ERG genes in the presence of both azoles. The matrix
      content presented a remarked decrease in proteins and an increase in
      carbohydrates, namely beta-1,3 glucans. Ergosterol was successfully detected and
      quantified in the biofilm matrices, with no differences in all the considered
      conditions. Vcz demonstrated better diffusion through the biofilms and better
      cell penetration capacities, than Flu, indicating that the structure of the drug
      molecule fully influences its dissemination through the biofilm matrices. This
      work showed that Vcz is notably more effective than Flu for the treatment of
      resistant C. glabrata oral biofilms, which demonstrates a clinical relevance in
      its future use for the treatment of oropharyngeal/esophageal candidiasis caused
      by this species.

PMID- 28439795
TI  - Age-based disparities in the use of total thyroidectomy for papillary thyroid
      carcinoma.
AB  - BACKGROUND: Elderly patients may be less likely than younger patients to receive
      indicated therapy. We hypothesized that older patients with papillary thyroid
      carcinoma (PTC) would be less likely to receive total thyroidectomy (TT) than
      their younger counterparts. MATERIALS AND METHODS: The Surveillance,
      Epidemiology, and End Results database were queried for adult patients diagnosed
      with PTC from 2000 through 2009. Patients were categorized according to whether
      they received a TT or less than a total thyroidectomy (<TT). We used multivariate
      logistic regression to predict the use of <TT. The likelihood of undergoing <TT
      was reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of
      the 67,961 patients identified with PTC, 51,276 (75%) received TT, 14,750 (22%)
      <TT and 1935 (3%) no surgery. On multivariate analysis, advancing age increased
      the likelihood of receiving <TT (age 45-54 OR 1.15, CI [1.09-1.20]; age 55-64 OR
      1.20, CI [1.14-1.26]; age 65-74 OR 1.40, CI [1.32-1.49]; 75-84 OR 1.80, CI [1.65
      1.95]; >=85 OR 3.01, CI [2.51-3.62], all p < 0.001). CONCLUSIONS: Older patients
      with PTC are less likely to receive TT. Further research is needed to assess if
      older patients are negatively impacted by less complete surgery.

PMID- 28439796
TI  - Adjuvant Endocrine Therapy in Breast Cancer: Evolving Paradigms in Premenopausal
      Women.
AB  - OPINION STATEMENT: In the last few years, new adjuvant endocrine treatment
      options have become available in young women with early breast cancer, such as
      the addition of ovarian function suppression to tamoxifen or aromatase
      inhibitors. Treatment duration has been also adapted in the latest guidelines
      based on the individual risk of recurrence. The oncologist is therefore
      challenged to precisely assess the risk of recurrence according to currently
      available predictive and prognostic factors in order to offer the most
      appropriate therapeutic option to the individual patient, considering also
      potential side effects, quality of life, pregnancy planning and patients'
      preferences. The adjuvant treatment planning should always be discussed and
      agreed in a multidisciplinary context. Tamoxifen remains the standard of care in
      low-risk patients or in case of intolerance to combined treatment with
      pharmacological ovarian function suppression or aromatase inhibitors. Combination
      treatment is indicated in intermediate high-risk disease. The patient should
      always be considered an active partner in the treatment decision process, to
      improve treatment motivation and adherence. Finally, the therapeutic choice
      should take into account drug availability and pharmacoeconomic issues, which
      unfortunately may prevent, in many low-income countries, the provision of such
      effective treatments.

PMID- 28439797
TI  - Desmoid-Type Fibromatosis: Who, When, and How to Treat.
AB  - OPINION STATEMENT: Desmoid-type fibromatosis is a sarcoma subtype that gathers
      some singular characteristics, making it a difficult challenge to face in
      clinical practice. Despite its excellent survival prognosis, these tumors may be
      unpredictable, ranging from an asymptomatic indolent course to persistent, local,
      and extended recurrences that significantly impair quality of life. Although
      surgery was initially considered the first elective treatment, collected
      published data during the past few years are now pointing to the "wait and see"
      approach as a reasonable initial strategy because many patients can live a long
      life with the disease without having symptoms. When symptoms appear or there is a
      risk of functional impairment, a wide spectrum of therapies (local and systemic)
      can be useful in improving symptoms and controlling the disease. Because of the
      low incidence of desmoid-type fibromatosis, there is scarce scientific evidence
      supporting any specific treatment. Nonetheless, if volumetric responses are
      needed, chemotherapy may be a reasonable early option. However, if long-term
      control of disease is desirable, hormonal therapy, NSAIDs, and TKIs are the
      likely treatments of choice. Recent new findings in the biologic development of
      these tumors, such as the role of Wnt/beta-catenin dependent pathway, have shown
      that the prognostic information provided by specific CTNNB1 gene mutations and
      other genetic profiles can lead to better methods of selecting patients as
      candidates for other approaches. Based on recent research, the Notch pathway
      inhibition in DF is one of the most promising potential targets to explore. As an
      orphan disease, it is mandatory that as many patients as possible be included in
      clinical trials.

PMID- 28439799
TI  - Internet Gaming Disorder among Adolescents.

PMID- 28439798
TI  - The Changing Landscape of Genetic Testing for Inherited Breast Cancer
      Predisposition.
AB  - OPINION STATEMENT: The advent of multiple-gene germline panel testing has led to
      significant advances in hereditary breast and ovarian cancer risk assessment.
      These include guideline-specific cancer risk management recommendations for
      patients and their families, such as screening with breast magnetic resonance
      imaging and risk-reducing surgeries, which have the potential to reduce
      substantially the morbidity and mortality associated with a hereditary cancer
      predisposition. However, controversy remains about the clinical validity and
      actionability of genetic testing in a broader patient population. We discuss
      events leading to the wider availability of commercialized multiple-gene germline
      panel testing, the recent data that support using this powerful tool to improve
      cancer risk assessment and reduction strategies, and remaining challenges to
      clinical optimization of this new genetic technology.

PMID- 28439800
TI  - Sub-conjunctival Hemorrhage Following a Bout of Cough: A Harbinger of Underlying
      Bleeding Diathesis.

PMID- 28439801
TI  - Extensive Retropharyngeal and Spinal Plexiform Neurofibromas in a Neonate with
      Type 1-Neurofibromatosis.

PMID- 28439802
TI  - Only a boost away from re-entry.

PMID- 28439803
TI  - Only a boost away from re-entry.

PMID- 28439804
TI  - Statistical analysis of arsenic contamination in drinking water in a city of Iran
      and its modeling using GIS.
AB  - In this research, probable arsenic contamination in drinking water in the city of
      Ardabil was studied in 163 samples during four seasons. In each season, sampling
      was carried out randomly in the study area. Results were analyzed statistically
      applying SPSS 19 software, and the data was also modeled by Arc GIS 10.1
      software. The maximum permissible arsenic concentration in drinking water defined
      by the World Health Organization and Iranian national standard is 10 MUg/L.
      Statistical analysis showed 75, 88, 47, and 69% of samples in autumn, winter,
      spring, and summer, respectively, had concentrations higher than the national
      standard. The mean concentrations of arsenic in autumn, winter, spring, and
      summer were 19.89, 15.9, 10.87, and 14.6 MUg/L, respectively, and the overall
      average in all samples through the year was 15.32 MUg/L. Although GIS outputs
      indicated that the concentration distribution profiles changed in four
      consecutive seasons, variance analysis of the results showed that statistically
      there is no significant difference in arsenic levels in four seasons.

PMID- 28439805
TI  - Microphytobenthic biomass, species composition and environmental gradients in the
      mangrove intertidal region of the Andaman Archipelago, India.
AB  - Monthly sampling in mangrove intertidal sediments of Andaman Archipelago was
      carried out during a 1-year study (January to December, 2013) in order to analyse
      the spatial and temporal distribution of microphytobenthos (MPB) and MPB biomass
      (sediment chlorophyll-a (chl-a)) in the surficial layer 0-1 cm. The MPB community
      was mainly composed of diatoms. The MPB biomass concentration in surface sediment
      (0-1 cm) ranged from 0.7 to 16.98 MUg cm-3. Population density of benthic diatoms
      varied from 78 to 224 ind cm-3. This study identified 41 diatom taxa (27 pennate
      diatoms, 14 centric diatoms) in the sediment, and among all the diatom taxa, we
      distinguished few true planktonic species-Coscinodiscus centralis, Coscinodiscus
      marginatus, Leptocylindricus danicus, Planktoniella sol, Thalassiosira decipiens,
      Thalassionema nitzschioides and Thalassiothrix longissima. Overall, a high
      percentage of diatoms were pennate (81%) as opposed to centric. Based on benthic
      diatom abundance, species composition and distribution, MPB assemblages of
      sampling stations were grouped into two distinct clusters: one with St. 1 and St.
      3 and another one with St. 2 and St. 4. Canonical correspondence analysis (CCA)
      revealed seasonality as the most important factor determining variability in
      diatom species composition among sampling sites. There was a distinct seasonal
      pattern in MPB biomass distribution and benthic diatom cell density during
      monsoon and post-monsoon seasons. Our results suggest that among various physical
      and chemical variables studied, greater levels of overlying water nutrients and
      sediment textures significantly correlated and were conducive factors for MPB.
      This is the first detailed study on the MPB from these mangrove sediments,
      providing benchmark data for future studies about these remote groups of Andaman
      and Nicobar Islands.

PMID- 28439806
TI  - A case of symptom relapse post placement of intrauterine device (IUD) in a
      patient with bulimia nervosa: consequence or coincidence.

PMID- 28439807
TI  - Generating explanations via analogical comparison.
AB  - Generating explanations can be highly effective in promoting learning in both
      adults and children. Our interest is in the mechanisms that underlie this effect
      and in whether and how they operate in early learning. In adult reasoning,
      explanation may call on many subprocesses-including comparison, counterfactual
      reasoning, and reasoning by exclusion; but it is unlikely that all these
      processes are available to young children. We propose that one process that may
      serve both children and adults is comparison. In this study, we asked whether
      children would use the results of a comparison experience when asked to explain
      why a model skyscraper was stable. We focused on a challenging principle-that
      diagonal cross-bracing lends stability to physical structures (Gentner et al.,
      Cognitive Science, 40, 224-240, 2016). Six-year-olds either received no training
      or interacted with model skyscrapers in one of three different conditions,
      designed to vary in their potential to invite and support comparison. In the
      Single Model condition, children interacted with a single braced model. In the
      comparison conditions (Low Alignability and High Alignability), children compared
      braced and unbraced models. Following experience with the models, children were
      asked to explain why the braced model was stable. They then received two transfer
      tasks. We found that children who received highly alignable pairs were most
      likely to (a) produce brace-based explanations and (b) transfer the brace
      principle to a dissimilar context. This provides evidence that children can
      benefit from analogical comparison in generating explanations and also suggests
      limitations on this ability.

PMID- 28439808
TI  - Timing a week later: The role of long-term memory in temporal preparation.
AB  - Temporal preparation has been investigated extensively by manipulating the
      foreperiod, the interval between a warning stimulus and target stimulus requiring
      a speeded response. Although such research has revealed many effects of both the
      duration and distribution of foreperiods on reaction times, the underlying
      cognitive mechanism is still largely unknown. Here, we test a recent proposal
      that temporal preparation is driven by the retrieval of memory traces of past
      experiences from long-term memory rather than by knowledge about upcoming events.
      Two groups of participants received different foreperiod distributions in an
      acquisition phase, which was followed a week later by a transfer phase, in which
      both groups received the same distribution of foreperiods. We found that the
      effects of the different foreperiod distributions presented in the acquisition
      phase were still apparent a week later during the transfer phase, as the reaction
      time patterns of both groups reflected the old distributions. This occurred even
      though both groups were provided with full information about the change in the
      distribution of foreperiods at the start of the transfer phase. These findings
      provide compelling evidence that long-term memory plays an important role in
      temporal preparation.

PMID- 28439810
TI  - QTLs and analysis of the candidate gene for amylose, protein, and moisture
      content in rice (Oryza sativa L.).
AB  - In this study, we determined using NIRS the heritability percentage of amylose,
      protein, and moisture content in polished and unpolished rice in a CNDH
      population derived from a cross between Cheongcheong and Nagdong rice varieties.
      The results revealed a higher heritability percentage for the amylose content and
      compromised heritability for protein and moisture contents. We also conducted QTL
      analysis of rice for these major components and identified their chromosomal
      locations on a physical map. We found a total of four QTLs affecting the amylose,
      protein, and moisture contents of grain on chromosome 7. We constructed physical
      maps of seven DNA markers responsible for amylose content, six responsible for
      protein content, and three responsible for moisture content. Furthermore, we
      classified these genes according to their functions and found 17 genes (over 77%)
      to be involved in secondary metabolite synthesis, two genes (about 9%), each
      related to cell function and abiotic stress, and one gene (about 5%) involved in
      redox signaling.

PMID- 28439809
TI  - Site Selection: a Case Study in the Identification of Optimal Cysteine Engineered
      Antibody Drug Conjugates.
AB  - As the antibody drug conjugate (ADC) community continues to shift towards site
      specific conjugation technology, there is a growing need to understand how the
      site of conjugation impacts the biophysical and biological properties of an ADC.
      In order to address this need, we prepared a carefully selected series of
      engineered cysteine ADCs and proceeded to systematically evaluate their potency,
      stability, and PK exposure. The site of conjugation did not have a significant
      influence on the thermal stability and in vitro cytotoxicity of the ADCs.
      However, we demonstrate that the rate of cathepsin-mediated linker cleavage is
      heavily dependent upon site and is closely correlated with ADC hydrophobicity,
      thus confirming other recent reports of this phenomenon. Interestingly,
      conjugates with high rates of cathepsin-mediated linker cleavage did not exhibit
      decreased plasma stability. In fact, the major source of plasma instability was
      shown to be retro-Michael mediated deconjugation. This process is known to be
      impeded by succinimide hydrolysis, and thus, we undertook a series of mutational
      experiments demonstrating that basic residues located nearby the site of
      conjugation can be a significant driver of succinimide ring opening. Finally, we
      show that total antibody PK exposure in rat was loosely correlated with ADC
      hydrophobicity. It is our hope that these observations will help the ADC
      community to build "design rules" that will enable more efficient prosecution of
      next-generation ADC discovery programs.

PMID- 28439811
TI  - Polymorphism analysis in identification of genetic variation and relationships
      among Stylosanthes species.
AB  - A total of 148 accessions representing six important species of the genus
      Stylosanthes, including S. guianensis, S. hamata, S. scabra, S. seabrana, S.
      macrocephala, and S. capitata, were used to evaluate genetic variation and
      relationships using sequence-related amplified polymorphism markers. The results
      showed that the 18 selected primer pairs generated 138 distinct fragments. The
      fragment sizes ranged from 150 to 2000 bp. Genetic similarity coefficients among
      the 148 accessions ranged from 0.51 to 0.99, with an average of 0.79. The
      effective allele number (ne) generated by the 18 primer pairs averaged 1.3552 and
      ranged from 1.2069 to 1.6080; Nei's gene diversity (He) ranged from 0.1304 to
      0.3207, with an average of 0.2070; and Shannon's information index (I) averaged
      0.3213 and ranged from 0.2233 to 0.4582. The unweighted pair-group method with
      arithmetic averages at the 0.69 similarity level separated the 148 accessions
      into two distinct groups. One group belonged to S. guianensis, and the other
      group belonged to the non-S. guianensis type. This study verified that
      Stylosanthes have rich genetic variation, which is an excellent basis for
      Stylosanthes breeding for new cultivars. This study demonstrates that the SRAP
      technique is a reliable tool for differentiating Stylosanthes accessions and for
      discerning genetic relationship among them.

PMID- 28439812
TI  - Amylase-assisted extraction and antioxidant activity of polysaccharides from
      Gracilaria lemaneiformis.
AB  - Gracilaria lemaneiformis (G. lemaneiformis) is rich in polysaccharides that have
      many functional activities. In this study, the thermostable alpha-amylase
      assisted extraction and antioxidant activity of water-soluble polysaccharides
      from G. lemaneiformis were investigated. The extraction conditions were optimized
      as follows: time, 40 min; temperature, 95  degrees C; pH, 5 and enzyme amount,
      6000 U/g, under which the yield of G. lemaneiformis polysaccharides (GPs) reached
      49.15% dry base. The GPs were characterized by monosaccharide composition, FTIR
      spectrum, UV spectrum and antioxidant activities. The results indicate that the
      GPs had strong hydroxyl radical activity at a concentration of 100 MUg/mL and
      could be used as potential antioxidants.

PMID- 28439813
TI  - Simultaneous heavy metal removal and anthracene biodegradation by the oleaginous
      bacteria Rhodococcus opacus.
AB  - This study investigated simultaneous heavy metals removal and anthracene
      biodegradation by Rhodococcus opacus at different initial anthracene
      concentrations in the range 50-200 mg L-1. The heavy metals tested were Fe(III),
      Cu(II), Zn(II), Cd(II), Ni(II), and Pb(II) at 10 mg L-1 initial concentration:
      The organism was found to be well capable of removing the heavy metals along with
      high anthracene biodegradation efficiency. However, anthracene biodegradation
      rate by the organism was reduced due to these heavy metals. In addition, the
      heavy metals effect on R. opacus biomass growth followed the order: Cd > Ni > Pb
      > Cu > Zn > Fe. The total time to anthracene biodegradation increased from 144 to
      216 h in the presence of Fe, Zn, Cu, or Pb, and it was up to 240 h in the
      presence of Cd or Ni. Compared with 70.2% (w/w) lipid accumulation by the
      bacterium in the absence of these heavy metals, a significant decline in the same
      was observed in the presence of the different heavy metals. These values were
      41.2, 44.1, 52.1, 54.1, 58.6, and 63.1% (w/w) for Cd, Ni, Pb, Cu, Zn, and Fe,
      respectively. Field emission scanning electron microscopy integrated with energy
      dispersive X-ray spectroscopy and transmission electron microscopy of the biomass
      grown in the presence and absence of these heavy metals further confirmed a
      change in morphology of the bacterium due to the heavy metals. Fourier
      transmission infrared spectroscopy spectra of the biomass obtained during its
      growth in the presence and absence of the heavy metals confirmed the involvement
      of N-H, C-H bend, -CH2-(C=O), C-N stretch, C-H and O-H bending, and -C-Cl groups
      on the biomass for heavy metal uptake by the bacterium.

PMID- 28439814
TI  - Imaging the accumulated intracellular microalgal lipids as a response to
      temperature stress.
AB  - Over the last few decades, many scientists considered microalgae as promising
      actors for future biofuels because of the high lipid productivity inside their
      cells. Moreover, much attention has been paid to algal lipids as they can be used
      in biodiesel production. In this study, we optimized the different suitable
      conditions such as incubation time, incubation temperature, Dimethylesulfoxide
      and Nile red concentrations of the lipophilic fluorescence dye Nile red as an
      excellent and fast vital stain to detect and quantify intracellular lipids. This
      was achieved using the green alga Nannochloropsis salina. In addition,
      investigating the accumulation of lipid vesicles inside different isolated
      microalgal species as a response to temperature stress. Furthermore, the confocal
      laser scanning microscopy (LS510) for imaging and measuring the size and volume
      of the accumulated lipid vesicles was used.

PMID- 28439816
TI  - Competitive Health Markets and Risk Equalisation in Australia: Lessons Learnt
      from Other Countries.
AB  - The aims of this paper are to evaluate the risk equalisation (RE) arrangement in
      Australia's private health insurance against practices in other countries with
      similar arrangements and to propose ways of improving the system to advance
      economic efficiency and solidarity. Possible regulatory responses to insurance
      market failures are reviewed based on standard economic arguments. We describe
      various regulatory strategies used elsewhere to identify essential system
      features against which the Australian system is compared. Our results reveal that
      RE is preferred over alternative regulatory strategies such as premium rate
      restrictions, premium compensation and claims equalisation. Compared with some
      countries' practices, the calculated risk factors in Australia should be enhanced
      with further demographic, social and economic factors and indicators of long-term
      health issues. Other coveted features include prospective calculation and annual
      clearing of equalisation payments. Australia currently operates with a crude
      mechanism for RE in which the scheme incentivises insurers to select on risk
      rather than focusing on efficiency and equity-promoting actions. System changes
      should be introduced in a stepwise manner; thus, we propose an incremental
      reform.

PMID- 28439815
TI  - The Effects of Voluntary Physical Exercise-Activated Neurotrophic Signaling in
      Rat Hippocampus on mRNA Levels of Downstream Signaling Molecules.
AB  - Physical exercise results in the increased expression of neurotrophic factors and
      the subsequent induction of signal transduction cascades with a positive impact
      on neuronal functions. In this study, we used a voluntary physical exercise rat
      model to determine correlations in hippocampus mRNA expression of the neurotropic
      factors Bdnf, VegfA, and Igf1; their receptors TrkB, Igf1R, VegfR1, and VegfrR2;
      and downstream signal transducers Creb, Syn1, and Vgf. In hippocampi of
      physically exercised rats, the mRNA expression levels of Bdnf transcript 4 (Bdnf
      t4), VegfA, and Igf1, as well as VegfR1, TrkB, Creb, Vgf, and Syn1, were
      increased. Bdnf-t4 mRNA expression positively correlated with mRNA expression of
      Creb, Vgf, and Syn1 in hippocampi of exercised rats. A correlation between Bdnf
      t4 and Syn1 mRNA expression was also observed in hippocampi of sedentary rats.
      Igf1 and VegfA mRNA expression was positively correlated in hippocampi of both
      exercised and sedentary rats. But, neither Igf1 nor VegfA mRNA expression was
      correlated with the expression of Bdnf-t4 or the expression of the signal
      transducers Creb, Syn1, and Vgf. In hippocampi of exercised rats, Creb mRNA
      expression was positively correlated with TrkB, Syn1, and Vgf mRNA expression and
      with the correlation between Creb and Vgf mRNA expression also observed in
      hippocampi of sedentary rats. To examine for causality of the in vivo observed
      correlated mRNA expression levels between Bdnf-t4 and the other examined
      transcripts, we used nuclease-deactivated CRISPR-Cas9 fused with VP64 to induce
      mRNA expression of endogenous Bdnf-t4 in rat PC12 cells. Following Bdnf-t4 mRNA
      induction, we observed increased Creb mRNA expression. This in vitro result is in
      accordance with the in vivo results and supports that under specified conditions,
      an increase in Creb mRNA expression can be a downstream signal transduction event
      due to induction of endogenous Bdnf mRNA expression.

PMID- 28439817
TI  - Developing the Totality of Evidence for Biosimilars: Regulatory Considerations
      and Building Confidence for the Healthcare Community.
AB  - Biosimilars are highly similar versions of approved branded biologics. Unlike
      generics, they are not exact replicas of reference products. Minor differences
      between biosimilars and reference products in some aspects are expected;
      likewise, biosimilar products will differ from each other. The objective of this
      review is to discuss the challenges associated with the development and approval
      of biosimilar products that are unique because of their complex structure and
      specialized manufacturing processes, which can impact not only efficacy but also
      immunogenicity and safety. Regulatory guidelines recommend a totality-of-evidence
      approach focused on stepwise development that involves demonstration of
      structural similarity and functional equivalence. Structural and functional
      characteristics of the proposed biosimilar are compared with the reference
      product; similarity of these functions forms the foundation of the biosimilar
      development program, including potential animal studies, a human
      pharmacokinetics/pharmacodynamics equivalence study, and a clinical study to
      confirm similar efficacy, safety, and immunogenicity. The clinical study should
      be performed in a sensitive population using appropriate endpoints to allow
      detection of any clinically meaningful differences between the biosimilar and the
      reference product if such differences exist. In conclusion, development of
      biosimilars is focused on the minimization of potential differences between the
      proposed biosimilar and reference product and the establishment of a robust
      manufacturing process to consistently produce a high-quality biosimilar product.

PMID- 28439818
TI  - Can experienced surgeons predict the additional value of a CT scan in patients
      with displaced intra-articular distal radius fractures?
AB  - There are no clear guidelines when an additional CT scan should be obtained for
      the treatment of displaced intra-articular distal radius fractures (DRF). This
      study aimed to investigate whether surgeons can predict the usefulness of CT
      scans to facilitate choice of treatment plan and/or pre-operative planning for
      DRF. Four surgeons evaluated 51 patients with displaced DRF. The choice of
      treatment (operative or nonoperative) was based on conventional radiographs.
      Subsequently, the surgeons were asked whether they would have requested an
      additional CT scan to determine this treatment choice, and also whether they
      required a CT scan for pre-operative planning. After 4 weeks, the additional CT
      scan was provided and the cases were assessed again. Based on these data, we
      calculated the number needed to scan (NNS) and number needed to harm (NNH) for
      two decision models. Model 1: Only provide a CT scan if the surgeon requested one
      based on their judgment of the X-rays. Model 2: CT scans for all displaced intra
      articular DRF. For choice of treatment, the NNS was lower for model 1 than for
      model 2 (2.6 vs. 4.3) and the NNH is higher for model 1 (3.1 vs. 1.3). For pre
      operative planning, the NNS (1.3 vs. 1.4) and NNH (3.7 vs. 3.4) were comparable
      for both models. Surgeons are able to predict the usefulness of an additional CT
      scan for intra-articular displaced DRF for OR indication. However, for pre
      operative planning the usefulness of a CT scan is much harder to predict.

PMID- 28439820
TI  - Erratum to: A Coupled Approach Utilizing Immunohistochemistry and
      Immunocytochemistry to Visualize Cellular Lipophagy.

PMID- 28439821
TI  - Epigenesis and the rationality of nature in William Harvey and Margaret
      Cavendish.
AB  - The generation of animals was a difficult phenomenon to explain in the
      seventeenth century, having long been a problem in natural philosophy, theology,
      and medicine. In this paper, I explore how generation, understood as epigenesis,
      was directly related to an idea of rational nature. I examine epigenesis-the idea
      that the embryo was constructed part-by-part, over time-in the work of two
      seemingly dissimilar English philosophers: William Harvey, an eclectic
      Aristotelian, and Margaret Cavendish, a radical materialist. I chart the ways
      that they understood and explained epigenesis, given their differences in
      philosophy and ontology. I argue for the importance of ideas of harmony and order
      in structuring their accounts of generation as a rational process. I link their
      experiences during the English Civil war to how they see nature as a possible
      source for the rationality and concord sorely missing in human affairs.

PMID- 28439819
TI  - Lengthening of the humerus with intramedullary lengthening nails-preliminary
      report.
AB  - Distraction osteogenesis of the humerus with fully implantable lengthening is now
      possible since the diameter of the available nails was reduced to 10 mm and
      below. We report on the first intramedullary lengthening cases of the humerus
      with two different lengthening devices (FITBONE and PRECICE). Two different
      approaches and implantation techniques were used. We retrospectively reviewed
      clinical and radiographic data and pointed out results, pitfalls and
      complications of the procedure. Four adult patients with relevant length
      discrepancy of the humerus were treated with fully implantable systems in two
      centers between 2012 and 2015. Three patients were treated with FITBONE by an
      antegrade approach; one patient had lengthening with a PRECICE and a retrograde
      approach. Average nail lengthening was 55 mm (40-65 mm), and the average duration
      of lengthening was 70 days (52-95 days). The average distraction index was 0.72
      mm/day (range 0.4-1.0 mm/day) or 12.5 days/cm (range 8.0-16.2 days/cm). The
      average consolidation index was 33.6 days/cm (range 25-45 days/cm). There was an
      implant failure (arrest) with the PRECICE. After consolidation and exchange with
      a technically improved implant, the course of treatment was uneventful. In
      patients with antegrade lengthening shoulder abduction decreased, and in the
      patient with the retrograde approach it improved but elbow extension decreased
      marginally. Reduced motion of the adjacent joints can be a major problem in
      intramedullary lengthening of the humerus. This first case series in the field of
      a rare indication suggests that lengthening of the humerus by fully implantable
      lengthening nails might be a valuable alternative to lengthening with external
      fixation. Main advantage of the PRECICE technology is the possible shortening in
      between of lengthening.

PMID- 28439822
TI  - Improved Denaturation of Small RNA Duplexes and Its Application for Northern
      Blotting.
AB  - Small RNAs (sRNAs) are short (18-30 nucleotide) noncoding RNA molecules, which
      control gene expression and pathogen response in eukaryotes. They are associated
      with and guide nucleases to target nucleic acids by nucleotide base pairing. We
      found that current techniques for small RNA detection are adversely affected by
      the presence of complementary RNA. Thus we established FDF-PAGE (fully denaturing
      formaldehyde polyacrylamide gel electrophoresis), which dramatically improves
      denaturation efficiency and subsequently the detection of sequestered sRNAs.

PMID- 28439823
TI  - High-Throughput RT-qPCR for the Analysis of Circulating MicroRNAs.
AB  - Reverse transcription followed by real-time or quantitative polymerase chain
      reaction (RT-qPCR) is the gold standard for validation of results from
      transcriptomic profiling studies such as microarray and RNA sequencing. The
      current need for most studies, especially biomarker studies, is to evaluate the
      expression levels or fold changes of many transcripts in a large number of
      samples. With conventional low to medium throughput qPCR platforms, many qPCR
      plates would have to be run and a significant amount of RNA input per sample will
      be required to complete the experiments. This is particularly challenging when
      the size of study material (small biopsy, laser capture microdissected cells,
      biofluid, etc.), time, and resources are limited. A sensitive and high-throughput
      qPCR platform is therefore optimal for the evaluation of many transcripts in a
      large number of samples because the time needed to complete the entire experiment
      is shortened and the usage of lab consumables as well as RNA input per sample are
      low. Here, the methods of high-throughput RT-qPCR for the analysis of circulating
      microRNAs are described. Two distinctive qPCR chemistries (probe-based and
      intercalating dye-based) can be applied using the methods described here.

PMID- 28439824
TI  - Genome-Wide Comparison of Next-Generation Sequencing and qPCR Platforms for
      microRNA Profiling in Serum.
AB  - This study compares next-generation sequencing (NGS) technologies that have been
      optimized specifically for biofluid samples, with more established qPCR-based
      methods for profiling microRNAs in biofluids. The same patient serum samples were
      analyzed by NGS and qPCR, and differences in the serum microRNA profile between
      HBV and HCV infected patients were investigated. While there was overall good
      agreement between NGS and qPCR, there were some differences between the
      platforms, highlighting the importance of validation.

PMID- 28439825
TI  - Small RNA Profiling by Next-Generation Sequencing Using High-Definition Adapters.
AB  - Small RNAs (sRNAs) as key regulators of gene expression play fundamental roles in
      many biological processes. Next-generation sequencing (NGS) has become an
      important tool for sRNA discovery and profiling. However, NGS data often show
      bias for or against certain sequences which is mainly caused by adapter
      oligonucleotides that are ligated to sRNAs more or less efficiently by RNA
      ligases. In order to reduce ligation bias, High-definition (HD) adapters for the
      Illumina sequencing platform were developed. However, a large amount of direct 5'
      and 3' adapter ligation products are often produced when the current commercially
      available kits are used for cloning with HD adapters. In this chapter we describe
      a protocol for sRNA library construction using HD adapters with drastically
      reduced direct 5' adapter-3' adapter ligation product. The protocol can be used
      for sRNA library preparation from total RNA or sRNA of various plant, animal,
      insect, or fungal samples. The protocol includes total RNA extraction from plant
      leaf tissue and cultured mammalian cells and sRNA library construction using HD
      adapters.

PMID- 28439826
TI  - Surface Acoustic Wave Lysis and Ion-Exchange Membrane Quantification of Exosomal
      MicroRNA.
AB  - MicroRNA detection and quantification are commonly explored techniques for
      diagnostic and prognostic predictions. Typically, microRNAs are extracted and
      purified from a biological source, converted into complementary DNA (cDNA), and
      amplified using real time polymerase chain reaction (RT-PCR). The number of RT
      PCR cycles required to reach the threshold of detection provides a relative
      quantification of the target microRNA when this data is normalized to the
      quantity of a control microRNA. This methodology has several drawbacks, including
      the need to artificially amplify the target microRNA for detection as well as
      quantification errors that can occur due to expression level differences of the
      control microRNAs for normalization in various sample sources. Here, we provide a
      technique to quantify actual concentrations of target microRNAs directly from any
      biological source without the requirement of these additional steps. In addition,
      we describe an alternative approach for obtaining exosomal microRNAs directly
      from biological samples without the use of harsh detergents and RNA isolation.

PMID- 28439827
TI  - Droplet Microfluidic Device Fabrication and Use for Isothermal Amplification and
      Detection of MicroRNA.
AB  - Droplet microfluidics combined with the isothermal circular strand displacement
      polymerization (ICSDP) represents a powerful new technique to detect both single
      stranded DNA and microRNA sequences. The method here described helps in
      overcoming some drawbacks of the lately introduced droplet polymerase chain
      reaction (PCR) amplification when implemented in microfluidic devices. The method
      also allows the detection of nanoliter droplets of nucleic acids sequences
      solutions, with a particular attention to microRNA sequences that are detected at
      the picomolar level. The integration of the ICSDP amplification protocol in
      droplet microfluidic devices reduces the time of analysis and the amount of
      sample required. In addition, there is also the possibility to design parallel
      analyses to be integrated in portable devices.

PMID- 28439828
TI  - Interrogation of Functional miRNA-Target Interactions by CRISPR/Cas9 Genome
      Engineering.
AB  - Post-transcriptional silencing by microRNAs (miRNAs) is a critical constituent of
      eukaryotic gene regulation. miRNAs are short (~22nt) noncoding RNAs capable of
      specifically targeting the miRNA-induced-silencing-complex (miRISC) to
      transcripts bearing a complementary miRNA response element (MRE). Although recent
      methodological advances have greatly improved our understanding of miRNA
      biogenesis and the mechanisms by which miRNAs repress their cognate targets,
      exploring the physiological relevance of direct miRNA-target interactions in vivo
      has remained an outstanding challenge. Here we describe the experimental protocol
      underlying a novel approach, which allows direct interrogation of specific miRNA
      MRE interactions by CRISPR/Cas9-mediated genome engineering. In this instance,
      the CRISPR/Cas9 system is first used to catalyze homology-directed replacement of
      candidate MREs with molecular barcodes at endogenous loci. Subsequently, the
      effect of MRE mutation on transcript abundance (i.e., MRE activity) can be
      rapidly evaluated by routine quantitative PCR. This strategy enables functional
      investigation of a putative miRNA-target pair in a pool of transiently
      transfected cells, obviating the need for generation of clonal cell lines or
      transgenic animals. This protocol can be implemented in any cell line in less
      than 2 weeks, and can readily be scaled up for multiplex studies. To facilitate
      the conceptual workflow underlying this strategy, we also describe a genome-wide
      resource for automated design and computational evaluation of CRISPR/Cas9 guide
      RNAs targeting all predicted MREs in various species (miR-CRISPR).

PMID- 28439829
TI  - Cell-Free Urinary MicroRNAs Expression in Small-Scale Experiments.
AB  - Cell-free microRNAs (miRNAs) have become one of the novel promising diagnostic
      and prognostic biomarkers for various diseases recently. Blood serum and plasma
      along with urine are the most common sources of clinically well, almost
      noninvasively available samples containing various types of miRNAs. Here, we
      present a protocol for a small-scale study investigating expression of several
      candidate miRNAs. Small-scale experiments may be worth investigating in cases
      where no information is available on miRNAs expression in particular diseases,
      for validation of previously published miRNAs with promising diagnostic
      potential, particularly in situations where follow-up study is aimed at
      validating miRNAs coming from array or NGS experiments, or where funding for
      these large-scale experiments is not available.Using urine miRNAs expression as
      the novel diagnostic tools is challenging and currently this approach is still in
      its infancy. Therefore, various methods may result in different conclusions
      depending on clinical sample sets and differences among methods used for the
      miRNAs isolation and quantitation. In this protocol, we present the method
      evaluated in the study focused on cell-free urinary miRNAs in ovarian and
      endometrial cancers. We recommend using stabilization tubes for the urine
      collection, as this step may be necessary to stop activity of RNases. Further,
      routine real-time PCR methods are described. We demonstrate that assessment of
      urinary miRNAs expression may reveal as a feasible method to explore the
      potential for finding novel diagnostic and prognostic markers.

PMID- 28439830
TI  - Peptide-Based Isolation of Argonaute Protein Complexes Using Ago-APP.
AB  - Argonaute (Ago) proteins bind small RNAs such as microRNAs (miRNAs) or short
      interfering RNAs (siRNAs), which guide them to distinct mRNAs for post
      transcriptional gene silencing. Mammalian miRNA-guided gene silencing pathways
      mainly lead to translational repression and mRNA destabilization. To facilitate
      these processes, Ago proteins bind members of the GW protein family, which form
      central interaction platforms for the recruitment of downstream effector
      proteins. GW proteins use tryptophane residues (W) to bind to the surface of Ago
      proteins. This high affinity interaction is retained when a short, GST-fused GW
      peptide is used in biochemical pull-down experiments-an approach referred to as
      "Ago Affinity Purification by Peptides" (Ago-APP). Since the binding interface is
      conserved among different paralogues and different species, Ago-APP represents a
      universal tool to purify Ago proteins and associated small RNAs using samples
      from species with conserved miRNA pathways.

PMID- 28439831
TI  - Predicting Functional MicroRNA-mRNA Interactions.
AB  - MicroRNAs (miRNAs) are small RNA molecules that play key regulatory roles in
      general biological processes and disease pathogenesis. These small RNA molecules
      interact with their target mRNAs to induce mRNA degradation and/or inhibit the
      translation of mRNAs into proteins. Therefore, identifying miRNA targets is an
      essential step to fully understand the regulatory effects of miRNAs. Here, we
      describe a regularized regression approach that integrates the sequence
      information with the miRNA and mRNA expression profiles for detecting miRNA
      targets. This method takes into account the full spectrum of gene sequence
      features of miRNA targets, including the thermodynamic stability, the
      accessibility energy, and the context features of the target sites,. Given these
      sequence features for each putative miRNA-mRNA interaction and their expression
      values, this model is able to quantify the down-regulation effect of each miRNA
      on its targets while simultaneously estimating the contribution of each sequence
      feature for predicting functional miRNA-mRNA interactions.

PMID- 28439832
TI  - Computational and Experimental Identification of Tissue-Specific MicroRNA
      Targets.
AB  - In this chapter we discuss computational methods for the prediction of microRNA
      (miRNA) targets. More specifically, we consider machine learning-based approaches
      and explain why these methods have been relatively unsuccessful in reducing the
      number of false positive predictions. Further we suggest approaches designed to
      improve their performance by considering tissue-specific target regulation. We
      argue that the miRNA targetome differs depending on the tissue type and introduce
      a novel algorithm that predicts miRNA targets specifically for colorectal cancer.
      We discuss features of miRNAs and target sites that affect target recognition,
      and how next-generation sequencing data can support the identification of novel
      miRNAs, differentially expressed miRNAs and their tissue-specific mRNA targets.
      In addition, we introduce some experimental approaches for the validation of
      miRNA targets as well as web-based resources sharing predicted and validated
      miRNA target interactions.

PMID- 28439833
TI  - sRNAtoolboxVM: Small RNA Analysis in a Virtual Machine.
AB  - High-throughput sequencing (HTS) data for small RNAs (noncoding RNA molecules
      that are 20-250 nucleotides in length) can now be routinely generated by
      minimally equipped wet laboratories; however, the bottleneck in HTS-based
      research has shifted now to the analysis of such huge amount of data. One of the
      reasons is that many analysis types require a Linux environment but computers,
      system administrators, and bioinformaticians suppose additional costs that often
      cannot be afforded by small to mid-sized groups or laboratories. Web servers are
      an alternative that can be used if the data is not subjected to privacy issues
      (what very often is an important issue with medical data). However, in any case
      they are less flexible than stand-alone programs limiting the number of workflows
      and analysis types that can be carried out.We show in this protocol how virtual
      machines can be used to overcome those problems and limitations. sRNAtoolboxVM is
      a virtual machine that can be executed on all common operating systems through
      virtualization programs like VirtualBox or VMware, providing the user with a high
      number of preinstalled programs like sRNAbench for small RNA analysis without the
      need to maintain additional servers and/or operating systems.

PMID- 28439834
TI  - An Assessment of the Next Generation of Animal miRNA Target Prediction
      Algorithms.
AB  - The advent of genome-wide next-generation sequencing technologies has
      revolutionized the genomic and transcriptomic fields. New technologies also
      present an opportunity for greater discovery and understanding of post
      transcriptional processes, in particular, translational inhibition of transcripts
      by miRBP (microRNA-RNA binding protein) complexes. Not only have novel
      methodologies been developed for the direct sequencing of RBP-bound RNA, but a
      new class of miRNA (microRNA) target prediction algorithms trained on this data
      has emerged. In this article, we will explore and evaluate the next generation of
      animal miRNA target prediction algorithms, their relationship to more traditional
      prediction methods, and the implications of such methodologies for the future of
      miRNA target prediction and miRNA research as a whole.

PMID- 28439835
TI  - The UEA Small RNA Workbench: A Suite of Computational Tools for Small RNA
      Analysis.
AB  - RNA silencing (RNA interference, RNAi) is a complex, highly conserved mechanism
      mediated by short, typically 20-24 nt in length, noncoding RNAs known as small
      RNAs (sRNAs). They act as guides for the sequence-specific transcriptional and
      posttranscriptional regulation of target mRNAs and play a key role in the fine
      tuning of biological processes such as growth, response to stresses, or defense
      mechanism.High-throughput sequencing (HTS) technologies are employed to capture
      the expression levels of sRNA populations. The processing of the resulting big
      data sets facilitated the computational analysis of the sRNA patterns of
      variation within biological samples such as time point experiments, tissue series
      or various treatments. Rapid technological advances enable larger experiments,
      often with biological replicates leading to a vast amount of raw data. As a
      result, in this fast-evolving field, the existing methods for sequence
      characterization and prediction of interaction (regulatory) networks periodically
      require adapting or in extreme cases, a complete redesign to cope with the data
      deluge. In addition, the presence of numerous tools focused only on particular
      steps of HTS analysis hinders the systematic parsing of the results and their
      interpretation.The UEA small RNA Workbench (v1-4), described in this chapter,
      provides a user-friendly, modular, interactive analysis in the form of a suite of
      computational tools designed to process and mine sRNA datasets for interesting
      characteristics that can be linked back to the observed phenotypes. First, we
      show how to preprocess the raw sequencing output and prepare it for downstream
      analysis. Then we review some quality checks that can be used as a first
      indication of sources of variability between samples. Next we show how the
      Workbench can provide a comparison of the effects of different normalization
      approaches on the distributions of expression, enhanced methods for the
      identification of differentially expressed transcripts and a summary of their
      corresponding patterns. Finally we describe individual analysis tools such as
      PAREsnip, for the analysis of PARE (degradome) data or CoLIde for the
      identification of sRNA loci based on their expression patterns and the
      visualization of the results using the software. We illustrate the features of
      the UEA sRNA Workbench on Arabidopsis thaliana and Homo sapiens datasets.

PMID- 28439836
TI  - Prediction of miRNA-mRNA Interactions Using miRGate.
AB  - miRGate ( http://mirgate.bioinfo.cnio.es /) is a freely available database that
      contains predicted and experimentally validated microRNA-messenger RNA (miRNA
      mRNA) target pairs. This resource includes novel predictions from five well
      established algorithms, but recalculated from a common and comprehensive sequence
      dataset. It includes all 3'-UTR sequences of all known genes of the three more
      widely employed genomes (human, mouse, and rat), and all annotated miRNA
      sequences from those genomes. Besides, it also contains predictions for all genes
      in human targeted by miRNA viruses such as Epstein-Barr and Kaposi sarcoma
      associated herpes virus.The approach intends to circumvent one of the main
      drawbacks in this area, as diverse sequences and gene database versions cause
      poor overlap among different target prediction methods even with experimentally
      confirmed targets. As a result, miRGate predictions have been successfully
      validated using functional assays in several laboratories.This chapter describes
      how a user can access target information via miRGate's web interface. It also
      shows how automatically access the database through the programmatic interface
      based on representational state transfer services (REST), using the application
      programming interface (API) available at http://mirgate.bioinfo.cnio.es/API .

PMID- 28439837
TI  - Detection of microRNAs Using Chip-Based QuantStudio 3D Digital PCR.
AB  - Digital PCR (dPCR) is an innovative approach for detection and quantification of
      nucleic acid that offers an alternative method to conventional real-time
      quantitative PCR for absolute quantification. dPCR is a highly precise and
      sensitive technique that does not require a standard reference, making it a
      suitable method for the detection of microRNAs. The potential of these small
      noncoding RNA as biomarkers is on the rise, especially due to their presence in
      body fluids, making them easily accessible. Nevertheless, the problem of lack of
      consensus regarding an optimal method for miRNAs normalization compromises their
      use. Here, we describe an innovative method for the absolute quantification of
      miRNAs across different types of biological samples using a chip-based platform,
      the QuantStudio 3D digital PCR.

PMID- 28439839
TI  - A Robust Protocol to Quantify Circulating Cancer Biomarker MicroRNAs.
AB  - Reverse-transcriptase quantitative PCR (RT-qPCR) is a widely used method for
      quantifying microRNAs (miRNAs) in cells and tissues. However, the quantification
      of miRNAs in the circulation presents specific challenges. Here, we describe an
      optimized protocol using a small amount of input material to assess serum sample
      quality and quantify levels of a panel of up to 20 miRNAs. This is achieved by
      multiplexing Taqman miRNA stem-loop primers in the reverse transcription step. An
      additional multiplexed pre-amplification step is used to increase the sensitivity
      of the final quantification step, which is carried out using standard Taqman qPCR
      methodology.

PMID- 28439838
TI  - MiRNA Quantitation with Microelectrode Sensors Enabled by Enzymeless
      Electrochemical Signal Amplification.
AB  - Quantification of circulating microRNAs (miRNAs) is of great interest because of
      their potentials as disease biomarkers. Currently, quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) and microarray are considered
      mainstream techniques for miRNA identification and quantitation. However, these
      techniques are challenged by the low levels and wide dynamic range (from aM to
      nM) of miRNAs in a physiological sample, as well as the difficulty in the
      implementation in point-of-care settings. Here, we describe a one-step label-free
      electrochemical sensing technique by assembling a triple-stem DNA-redox probe
      structure on a gold microelectrode and introducing a reductant, tris(2
      carboxyethyl) phosphine hydrochloride (TCEP) in the detection buffer solution to
      achieve ultrasensitive miRNAs detection with a detection limit of 0.1 fM.

PMID- 28439840
TI  - MicroRNAs, Regulatory Networks, and Comorbidities: Decoding Complex Systems.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional
      regulation of messenger RNAs (mRNAs). Each miRNA targets a specific set of mRNAs.
      Upon binding the miRNA inhibits mRNA translation or facilitate mRNA degradation.
      miRNAs are frequently deregulated in several pathologies including cancer and
      cardiovascular diseases. Since miRNAs have a crucial role in fine-tuning the
      expression of their targets, they have been proposed as biomarkers of disease
      progression and prognostication.In this chapter we discuss different approaches
      for computational predictions of miRNA targets based on sequence complementarity
      and integration of expression data. In the last section of the chapter we discuss
      new opportunities in the study of miRNA regulatory networks in the context of
      temporal disease progression and comorbidities.

PMID- 28439841
TI  - Label-Free Direct Detection of MiRNAs with Poly-Silicon Nanowire Biosensors.
AB  - The diagnostic and prognostic value of microRNAs (miRNAs) in diseases becomes
      promising. Owing to fast response and high sensitivity, silicon nanowire (SiNW)
      biosensor has been considered a potential tool for miRNAs detection. Here, we
      describe a booming method to detect miRNAs with poly-silicon nanowire biosensors.
      Standard and real miRNA samples are applied in this study. The results show a
      limitation of 1 fM in the detection of standard miRNA sample with our poly
      nanowire devices. Meanwhile, one-base mismatched sequence could be distinguished.
      Furthermore, these poly-SiNW arrays can detect snRNA U6 in total RNA samples
      extracted from HepG2 cells with a detection limitation of 0.2 MUg/mL.

PMID- 28439843
TI  - Effective dose estimation for oncological and neurological PET/CT procedures.
AB  - BACKGROUND: The aim of this study was to retrospectively evaluate the patient
      effective dose (ED) for different PET/CT procedures performed with a variety of
      PET radiopharmaceutical compounds. PET/CT studies of 210 patients were reviewed
      including Torso (n = 123), Whole body (WB) (n = 36), Head and Neck Tumor (HNT) (n
      = 10), and Brain (n = 41) protocols with 18FDG (n = 170), 11C-CHOL (n = 10),
      18FDOPA (n = 10), 11C-MET (n = 10), and 18F-florbetapir (n = 10). ED was
      calculated using conversion factors applied to the radiotracer activity and to
      the CT dose-length product. RESULTS: Total ED (mean +/- SD) for Torso-11C-CHOL,
      Torso-18FDG, WB-18FDG, and HNT-18FDG protocols were 13.5 +/- 2.2, 16.5 +/- 4.5,
      20.0 +/- 5.6, and 15.4 +/- 2.8 mSv, respectively, where CT represented 77, 62,
      69, and 63% of the protocol ED, respectively. For 18FDG, 18FDOPA, 11C-MET, and
      18F-florbetapir brain PET/CT studies, ED values (mean +/- SD) were 6.4 +/- 0.6,
      4.6 +/- 0.4, 5.2 +/- 0.5, and 9.1 +/- 0.4 mSv, respectively, and the
      corresponding CT contributions were 11, 14, 23, and 26%, respectively. In 18FDG
      PET/CT, variations in scan length and arm position produced significant
      differences in CT ED (p < 0.01). For dual-time-point imaging, the CT ED (mean +/-
      SD) for the delayed scan was 3.8 +/- 1.5 mSv. CONCLUSIONS: The mean ED for body
      and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6
      and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas
      for brain studies, it is the PET radiopharmaceutical.

PMID- 28439842
TI  - Controversies in the multimodality management of locally advanced rectal cancer.
AB  - Neoadjuvant radiotherapy previous to radical surgery, both as short-course
      radiotherapy and as long-course radiotherapy combined with 5-FU-based
      chemotherapy (LCRCT), is routinely used in the management of locally advanced
      rectal cancer, with consistent benefits in the reduction in the local relapse
      risk. Unfortunately, survival benefits have been elusive to demonstrate with this
      approach, especially in the setting of radical surgery in the form of total
      mesorectal excision (TME). Concerns about over-treating early-stage patients and
      about the possible long-term side effects have also cast more doubts in a blanket
      approach of treating all patients with neoadjuvant radiotherapy, especially with
      LCRCT. In this review of selected controversial topics in locally advanced rectal
      cancer, we examine the benefits and drawbacks for the use of both neoadjuvant
      approaches in the TME era, the role of the intensification of the neoadjuvant
      regimens with new chemotherapy agents and modifications of the radiotherapy
      regimen, the usefulness of adjuvant chemotherapy, especially after LCRCT and
      surgery, and the management of elderly and/or frail patients. Finally, we offer
      some future perspectives in the management of these patients.

PMID- 28439844
TI  - Therapeutic efficacy of alpha-radioimmunotherapy with different activity levels
      of the 213Bi-labeled monoclonal antibody MX35 in an ovarian cancer model.
AB  - BACKGROUND: The aim of this study was to compare the therapeutic efficacy of two
      different activity levels of the 213Bi-labeled monoclonal antibody MX35 in an
      ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated
      intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40
      mice were injected intraperitoneal (i.p.) with 1 ml of 213Bi-MX35, 3 MBq/mL (n =
      20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35.
      Incidence of tumors and ascites was investigated 8 weeks after therapy. Body
      weight and white blood cell counts were monitored after treatment for possible
      signs of toxicity. RESULTS: The tumor-free fraction of the animals treated with 3
      MBq/mL of 213Bi-MX35 was 0.55, whereas that of animals treated with 9 MBq/mL of
      213Bi-MX35 was 0.78. The control group treated with unlabeled MX35 had a tumor
      free fraction of 0.15. No significant reduction in white blood cell counts or
      weight loss was observed. CONCLUSIONS: Tumor growth after i.p. treatment with
      213Bi-MX35 was significantly reduced compared to treatment with unlabeled MX35.
      Treatment with 9 MBq/mL of 213Bi-MX35 resulted in higher tumor-free fraction
      compared with 3 MBq/mL of 213Bi-MX35, but this difference was not statistically
      significant. No signs of toxicity were observed in the treated animals.

PMID- 28439846
TI  - Partnership for a Healthier America: Creating Change Through Private Sector
      Partnerships.
AB  - PURPOSE OF REVIEW: This review provides background on the formation of the
      Partnership for a Healthier America (PHA), that was created in conjunction with
      the Let's Move! initiative, and an overview of its work to date. RECENT FINDINGS:
      To encourage industry to offer and promote healthier options, PHA partners with
      the private sector. Principles that guide PHA partnerships include ensuring that
      partnerships represent meaningful change, partners sign a legally binding
      contract and progress is monitored and publicly reported. Since 2010, PHA has
      established private sector partnerships in an effort to transform the marketplace
      to ensure that every child has the chance to grow up at a healthy weight. Many
      agreements between PHA and its industry partners align with the White House Task
      Force Report on Childhood Obesity. The reach and impact of over 200 partnerships
      attest to the success of this initiative.

PMID- 28439845
TI  - A Systematic Review of the Clinical Presentation, Diagnosis, and Treatment of
      Small Bowel Obstruction.
AB  - PURPOSE OF REVIEW: This study aimed to systematically review small bowel
      obstruction (SBO), focusing on recent changes in diagnosis/therapy. RECENT
      FINDINGS: SBO incidence is about 350,000/annum in the USA. Etiologies include
      adhesions (65%), hernias (10%), neoplasms (5%), Crohn's disease (5%), and other
      (15%). Bowel dilatation occurs proximal to obstruction primarily from swallowed
      air and secondarily from intraluminal fluid accumulation. Dilatation increases
      mural tension, decreases mucosal perfusion, causes bacterial proliferation, and
      decreases mural tensile strength that increases bowel perforation risks.
      Classical clinical tetrad is abdominal pain, nausea and emesis, abdominal
      distention, and constipation-to-obstipation. Physical exam may reveal
      restlessness, acute illness, and signs of dehydration and sepsis, including
      tachycardia, pyrexia, dry mucous membranes, hypotension/orthostasis, abdominal
      distention, and hypoactive bowel sounds. Severe direct tenderness, involuntary
      guarding, abdominal rigidity, and rebound tenderness suggest advanced SBO, as do
      marked leukocytosis, neutrophilia, bandemia, and lactic acidosis. Differential
      diagnosis includes postoperative ileus, narcotic bowel, colonic pseudo
      obstruction, mesenteric ischemia, and large bowel obstruction. Medical
      resuscitation includes intravenous hydration, correcting electrolyte
      abnormalities, intravenous antibiotics, nil per os, and nasoenteral suction.
      Abdominal CT with oral and intravenous gastrografin contrast is highly sensitive
      and specific in detecting/characterizing SBO. SBO usually resolves with medical
      therapy but requires surgery, preferentially by laparoscopy, for unremitting
      total obstruction, bowel perforation, severe ischemia, or clinical deterioration
      with medical therapy. Overall mortality is 10% but increases to 30% with bowel
      necrosis/perforation. Key point in SBO is early diagnosis, emphasizing abdominal
      CT; aggressive medical therapy including rehydration, antibiotics, and nil per
      os; and surgery for failed medical therapy.

PMID- 28439847
TI  - The Role of the FDA and Regulatory Approval of New Devices for Diabetes Care.
AB  - PURPOSE OF REVIEW: The Food and Drug Administration (FDA) is responsible for
      assuring the safety, effectiveness, and quality of medical devices in the USA.
      Extensive review times coupled with the demand for necessary treatments have
      prompted the policymakers to implement measures to speed medical devices to
      market.The purpose of this review is to summarize the evolution of the regulatory
      pathways through which medical devices utilized in diabetes care gain market
      access. RECENT FINDINGS: Regulatory pathways, ranging from premarket notification
      to premarket approval, require distinct, yet necessary ("least burdensome")
      evidence demonstrating a device's safety and effectiveness. Collaboration between
      manufacturers, regulators, and patients has resulted in the development and
      approval of novel diabetes care devices, including the first hybrid closed-loop
      artificial pancreas. Policy provisions, ranging from the least burdensome
      approach to the "breakthrough device" expedited pathway, aim to balance
      innovation, access, and safety. Clinicians must be aware of the evolving
      regulatory landscape and play an active role in enhancing patient safety.

PMID- 28439849
TI  - Aortic valve replacement after coronary artery bypass grafting with the in situ
      right gastroepiploic artery to the occluded right coronary artery using a
      temporary vein graft for cardioplegia.
AB  - BACKGROUND: The operation of aortic valve replacement (AVR) after CABG is a
      technically challenging procedure in respect to dissection of living grafts from
      its surrounding tissue, myocardial protection, and so on, especially that
      procedure to patients with living in situ functional arterial grafts to occluded
      native coronary arteries has a special problem in regard to myocardial protection
      because myocardial blood supply originates from various arteries including the
      left internal thoracic artery (LITA), the right internal thoracic artery (RITA),
      and the right gastroepiploic artery (GEA); hence, adequate myocardial protection
      should be fastidiously considered. CASE PRESENTATION: A 68-year-old woman, who
      underwent CABG comprised of the in situ LITA to the LAD, the in situ GEA to the
      RCA, and the saphenous vein graft (SVG) to the obtuse marginal branch of the left
      circumflex artery (LCX) to the triple vessel coronary disease 9 years before, was
      referred to our hospital due to the aortic valve stenosis. CONCLUSION: We
      successfully underwent an aortic valve operation to a patient with a functioning
      LITA to the occluded left anterior descending artery and a GEA to the right
      coronary artery (RCA) by using a temporary vein graft to the RCA for the infusion
      of cardioplegic solution in addition to the conventional antegrade and retrograde
      cardioplegic infusions with ice slush topical cooling.

PMID- 28439848
TI  - The Janus Head of Oxidative Stress in Metabolic Diseases and During Physical
      Exercise.
AB  - PURPOSE OF REVIEW: Oxidative stress describes an imbalance between production and
      degradation of reactive oxygen species (ROS), which can damage macromolecules.
      However, ROS may also serve as signaling molecules activating cellular pathways
      involved in cell proliferation and adaptation. This review describes alterations
      in metabolic diseases including obesity, insulin resistance, and/or diabetes
      mellitus as well as responses to acute and chronic physical exercise. RECENT
      FINDINGS: Chronic upregulation of oxidative stress associates with the
      development of insulin resistance and type 2 diabetes (T2D). While single bouts
      of exercise can transiently induce oxidative stress, chronic exercise promotes
      favorable oxidative adaptations with improvements in muscle mitochondrial
      biogenesis and glucose uptake. Although impaired antioxidant defense fails to
      scavenge ROS in metabolic diseases, chronic exercising can restore this
      abnormality. The different metabolic effects are likely due to variability of
      reactive species and discrepancies in temporal (acute vs. chronic) and local
      (subcellular distribution) patterns of production.

PMID- 28439850
TI  - Heterologous expression of a Streptomyces cyaneus laccase for biomass
      modification applications.
AB  - Laccases are used for the conversion of biomass into fermentable sugars but it is
      difficult to produce high yields of active laccases in heterologous expression
      systems. We overcame this challenge by expressing Streptomyces cyaneus CECT 3335
      laccase in Escherichia coli (ScLac) and we achieved a yield of up to 104 mg L-1
      following purification by one-step affinity chromatography. Stability and
      activity assays using simple lignin model substrates showed that the purified
      enzyme preparation was active over a broad pH range and at high temperatures,
      suggesting it would be suitable for biomass degradation. The reusability of ScLac
      was also demonstrated by immobilizing the enzyme on agarose beads with a binding
      yield of 33%, and by the synthesis of cross-linked enzyme aggregates with an
      initial activity recovery of 72%.

PMID- 28439851
TI  - Exploring the Pathophysiology of Takotsubo Cardiomyopathy.
AB  - PURPOSE OF REVIEW: The purpose of this review is to explore the pathophysiology
      of Takotsubo cardiomyopathy by appraising the interplay between myocardial
      perfusion, function, metabolism, and, particularly, sympathetic innervation.
      RECENT FINDINGS: A number of hypotheses have been proposed to explain the
      pathogenesis of Takotsubo cardiomyopathy, which include (1) catecholamine cardiac
      toxicity, (2) myocardial sympathetic innervation disruption, (3) coronary
      vasospasm, (4) myocardial microvascular dysfunction, and (5) aborted myocardial
      infarction. These proposals are primarily derived from findings of nuclear
      myocardial perfusion, metabolism, and cardiac sympathetic innervation imaging.
      Although data in the literature are not necessarily uniform, the two most
      plausible working postulates for explaining the phenomenon are (1) regional
      myocardial stunning (due to coronary vasospasm, microvascular dysfunction, or
      aborted myocardial infarction) and (2) cardiac sympathetic innervation disruption
      or toxicity. Current data suggest that disturbances of both coronary circulation
      and neural innervation are associated with the Takotsubo cardiomyopathy:
      myocardial stunning from transient ischemic attack and sympathetic innervation
      disruption. It remains to be determined, however, whether the observed leading
      mechanistic explanations that have gained momentum are merely the sequelae of the
      disease rather than its primary etiology.

PMID- 28439853
TI  - CRISPR/Cas-Mediated In Planta Gene Targeting.
AB  - The recent emergence of the CRISPR/Cas system has boosted the possibilities for
      precise genome engineering approaches throughout all kingdoms of life. The most
      common application for plants is targeted mutagenesis, whereby a Cas9-mediated
      DNA double-strand break (DSB) is repaired by mutagenic nonhomologous end joining
      (NHEJ). However, the site-specific alteration of a genomic sequence or
      integration of a transgene relies on the precise repair by homologous
      recombination (HR) using a suitable donor sequence: this poses a particular
      challenge in plants, as NHEJ is the preferred repair mechanism for DSBs in
      somatic tissue. Here, we describe our recently developed in planta gene targeting
      (ipGT) system, which works via the induction of DSBs by Cas9 to activate the
      target and the targeting vector at the same time, making it independent of high
      transformation efficiencies.

PMID- 28439852
TI  - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Concise Review with a
      Comprehensive Summary of Therapeutic Interventions Emphasizing Supportive
      Measures.
AB  - INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are two of the most severe dermatologic conditions occurring in the inpatient
      setting. There is a lack of consensus regarding appropriate management of SJS and
      TEN. PURPOSE: The scientific literature pertaining to SJS and TEN (subsequently
      referred to as SJS/TEN) is summarized and assessed. In addition, an
      interventional approach for the clinician is provided. METHODS: PubMed was
      searched with the key words: corticosteroids, cyclosporine, etanercept,
      intravenous immunoglobulin, Stevens-Johnson syndrome, and toxic epidermal
      necrolysis. The papers generated by the search, and their references, were
      reviewed. RESULTS: Supportive care is the most universally accepted intervention
      for SJS/TEN. Specific guidelines differ from the care required for patients with
      thermal burns. Adjuvant therapies are utilized in most severe cases, but the data
      are thus far underwhelming and underpowered. Using systemic corticosteroids as
      sole therapy is not supported. A consensus regarding combined corticosteroids and
      intravenous immunoglobulin (IVIG) has not been reached. Data regarding IVIG,
      currently the standard of care for most referral centers, is conflicting. Newer
      studies regarding cyclosporine and tumor necrosis factor inhibitors are
      promising, but not powered to provide definitive evidence of efficacy. Data
      regarding plasmapheresis is equivocal. Thalidomide increases mortality.
      CONCLUSION: Clinicians who manage SJS/TEN should seek to employ interventions
      with the greatest impact on their patients' condition. While supportive care
      measures may seem an obvious aspect of SJS/TEN patient care, providers should
      understand that these interventions are imperative and that they differ from the
      care recommended for other critically ill or burn patients. While adjuvant
      therapies are frequently discussed and debated for hospitalized patients with
      SJS/TEN, a standardized management approach is not yet clear based on the current
      data. Therefore, until further data are available, decisions regarding such
      treatments should be made on a case-by-case basis.

PMID- 28439854
TI  - User Guide for the LORE1 Insertion Mutant Resource.
AB  - Lotus japonicus is a model legume used in the study of plant-microbe
      interactions, especially in the field of biological nitrogen fixation due to its
      ability to enter into a symbiotic relationship with a soil bacterium,
      Mesorhizobium loti. The LORE1 mutant population is a valuable resource for
      reverse genetics in L. japonicus due to its non-transgenic nature, high tagging
      efficiency, and low copy count. Here, we outline a workflow for identifying,
      ordering, and establishing homozygous LORE1 mutant lines for a gene of interest,
      LjFls2, including protocols for growth and genotyping of a segregating LORE1
      population.

PMID- 28439855
TI  - Enabling Reverse Genetics in Medicago truncatula Using High-Throughput Sequencing
      for Tnt1 Flanking Sequence Recovery.
AB  - The genome sequence of Medicago truncatula was published and released in 2011. A
      Tnt1 insertional mutant population with 21,700 independently regenerated lines
      was completed in 2012 at The Samuel Roberts Noble Foundation. With an estimated
      25 insertions per line, the Tnt1 mutant population harbors more than 500,000
      insertions in the M. truncatula genome. Based on the genome size, average gene
      length, and random insertion of Tnt1into the genome, the mutant population
      affects about 90% of genes in the M. truncatula genome. Therefore, the mutant
      population enables functional characterization of most genes in the M. truncatula
      genome. From 2006 to 2011, we sequenced about 33,000 flanking sequence tags
      (FSTs) from 2600 Tnt1 lines using TAIL-PCR followed by TA cloning, plasmid
      isolation, and traditional Sanger sequencing. To accelerate FST sequencing, we
      developed a two-dimensional DNA pooling strategy coupled with next-generation
      sequencing and produced about 380,000 FSTs from all 21,700 lines in a relatively
      short time. All FSTs are BLAST searchable in a web-based database. One can
      quickly search the database to find M. truncatula mutant lines with Tnt1
      insertions in most genes of interest.

PMID- 28439856
TI  - The Generation of Doubled Haploid Lines for QTL Mapping.
AB  - Recombinant inbred lines (RILs) are an essential tool for quantitative trait
      locus (QTL) mapping in Arabidopsis thaliana. Conventionally, the development of
      these lines is a time-consuming and tedious process requiring six to eight
      generations of selfing. Here, we describe an alternative approach: the rapid
      generation of RILs in A. thaliana via the creation of doubled haploids. In this
      method, F1 plants are crossed to an engineered haploid inducer to produce haploid
      plants. The chromosomes of these haploids then spontaneously double, generating
      immortalized homozygous F2 lines called doubled haploid RILs (DH RILs). Finally,
      DH RILs are genotyped using low-coverage whole-genome sequencing and are ready to
      be used for QTL mapping.

PMID- 28439857
TI  - Assessing Distribution and Variation of Genome-Wide DNA Methylation Using Short
      Read Sequencing.
AB  - DNA methylation is one of the most prominent epigenetic marks and is particularly
      complex in plant genomes. Whole-genome bisulfite sequencing (WGBS) using short
      reads has become the standard tool to study genome-wide patterns of DNA
      methylation. The goal of the present protocol is to enable readers to perform
      WGBS on both the wet lab and the computational side. We briefly outline important
      steps in bisulfite library preparation, then focus on the different aspects of
      DNA methylation analysis, from read mapping to identifying biologically relevant
      differential methylation between different samples.

PMID- 28439858
TI  - Circular Chromosome Conformation Capture in Plants.
AB  - The study of nuclear architecture promises novel insights into genome function
      and regulation. Hereby, quantitative methods based on chromosome conformation
      capture (3C) revolutionized the field, as they allow accurate and unbiased
      characterization of 3D genome organization of genomic regions of interest. The
      choice of the appropriate 3C derivate is crucial to acquire results suited for a
      specific research question. Circular 3C (4C) is the method of choice to study the
      genome-wide 3D architecture of a specific genomic region of interest. Here, I
      present a robust 4C protocol, established in Arabidopsis thaliana, which can be
      employed by any experienced molecular biologist and is applicable in various
      other plant species.

PMID- 28439859
TI  - Genome-Wide Profiling of Histone Modifications and Histone Variants in
      Arabidopsis thaliana and Marchantia polymorpha.
AB  - Histone modifications and histone variants barcode the genome and play major
      roles in epigenetic regulations. Chromatin immunoprecipitation (ChIP) coupled
      with next-generation sequencing (NGS) is a well-established method to investigate
      the landscape of epigenetic marks at a genomic level. Here, we describe
      procedures for conducting ChIP, subsequent NGS library construction, and data
      analysis on histone modifications and histone variants in Arabidopsis thaliana.
      We also describe an optimized nuclear isolation procedure to prepare chromatin
      for ChIP in the liverwort, Marchantia polymorpha, which is the emerging model
      plant ideal for evolutionary studies.

PMID- 28439860
TI  - Tissue-Specific Transcriptome Profiling in Arabidopsis Roots.
AB  - Spatiotemporal transcriptome profiles from specific tissues are critical for
      understanding plant development and responses to the environment. One approach to
      isolate specific tissues is fluorescence-activated cell sorting (FACS). In this
      chapter, we outline methods for the FACS isolation of root protoplasts followed
      by transcriptome profiling using RNA sequencing.

PMID- 28439861
TI  - Sample Preparation Protocols for Protein Abundance, Acetylome, and
      Phosphoproteome Profiling of Plant Tissues.
AB  - Peptide mass spectrometry is an invaluable technique to globally quantify the
      proteome. Central to proteome profiling are efficient methods to extract
      proteins, digest proteins into peptides, and enrich for posttranslationally
      modified peptides prior to mass spectrometry. In this chapter, we describe
      methods to extract proteins, process them into peptides, and optionally enrich
      for phospho- and acetyl-peptides prior to analysis by mass spectrometry.

PMID- 28439863
TI  - Large-Scale Phenotyping of Root Traits in the Model Legume Lotus japonicus.
AB  - Plants are sessile organisms that can tune their body architecture to the
      environment. This is very pronounced in their root system. In particular,
      nutrient availability strongly influences the architecture of the root system;
      depending on the abundance of specific nutrients, root growth rates and lateral
      root number are modulated. The extent of these effects is important for plant
      adaptation and has a major impact on plant fitness. However, the assessment of
      quantitative effects on a scale large enough for identifying genes and variants
      using quantitative genetics is difficult, and well-developed methods have been
      largely restricted to the model species Arabidopsis thaliana. In this chapter, we
      present a protocol for high-throughput phenotyping of early root traits in the
      model legume plant Lotus japonicus. This species allows for the study of
      important root-associated traits that are not present in Arabidopsis, such as
      symbioses with nitrogen-fixing Rhizobia and arbuscular mycorrhizal fungi. The
      methods described in this chapter can be used in the context of reverse and
      forward genetics approaches to dissect the genetic basis of root growth in
      legumes.

PMID- 28439862
TI  - Automated High-Throughput Root Phenotyping of Arabidopsis thaliana Under Nutrient
      Deficiency Conditions.
AB  - The central question of genetics is how a genotype determines the phenotype of an
      organism. Genetic mapping approaches are a key for finding answers to this
      question. In particular, genome-wide association (GWA) studies have been rapidly
      adopted to study the architecture of complex quantitative traits. This was only
      possible due to the improvement of high-throughput and low-cost phenotyping
      methodologies. In this chapter we provide a detailed protocol for obtaining root
      trait data from the model species Arabidopsis thaliana using the semiautomated,
      high-throughput phenotyping pipeline BRAT (Busch-lab Root Analysis Toolchain) for
      early root growth under the stress condition of iron deficiency. Extracted root
      trait data can be directly used to perform GWA mapping using the freely
      accessible web application GWAPP to identify marker polymorphisms associated with
      the phenotype of interest.

PMID- 28439864
TI  - Long-Term Confocal Imaging of Arabidopsis thaliana Roots for Simultaneous
      Quantification of Root Growth and Fluorescent Signals.
AB  - Observing cellular and molecular processes in living organisms is key for
      understanding many important biological processes. Confocal microscopy is
      excellently suited for this as it enables the observation of molecules and cells
      in tissue layers of living organisms in three dimensions over time. However, in
      continuously growing organs, such as plant roots, observations over extended time
      spans become difficult as the specimen quickly grows out the field of view. Here,
      we provide a protocol that allows for the acquisition of confocal microscope time
      lapse images of root tips spanning many hours, as the growing root tip is tracked
      and the microscopy is automatized to change the position of the stage.
      Importantly, due to its specific setup, this protocol allows for observing the
      effects of chemical stimuli or for creating specific growth conditions by
      precisely defining the growth medium during imaging. The protocol is suitable for
      observing multiple fluorophores, thereby moving beyond the level of individual
      genes. It is also simple enough to conduct larger numbers of these assays. Here
      we exemplify our method by describing the observation of root growth and GFP
      intensity in root tips under iron depletion conditions.

PMID- 28439865
TI  - Identification of Protein-DNA Interactions Using Enhanced Yeast One-Hybrid Assays
      and a Semiautomated Approach.
AB  - Yeast one-hybrid assays are an in vitro gene-centered approach to map
      transcription factor-DNA interactions. Here we describe this method and
      adaptations to screen for interactions between plant transcriptional regulators
      and their targets. Of particular note, the use of yeast one-hybrid assays fills
      in an important gap in available methodologies. When one is interested in a
      specific biological process of interest, the yeast one-hybrid assay is the only
      method that allows researchers to identify upstream regulators of the biological
      process of interest. This technique can be also used to further validate physical
      protein-DNA interactions or as a hypothesis-generating tool. In this method,
      promoters or DNA regions of interest are cloned and transformed into yeast and
      tested for interaction against a collection of transcription factors (TFs). Yeast
      one-hybrid screens are adaptable to the question the researcher is asking and the
      tools and components available. In this chapter we will describe large-scale and
      high-throughput Y1H screening; however, this can easily be scaled down for
      smaller studies.

PMID- 28439866
TI  - Mapping Protein-Protein Interaction Using High-Throughput Yeast 2-Hybrid.
AB  - A tremendous asset to the analysis of protein-protein interactions is the yeast-2
      hybrid (Y2H) method. The Y2H assay is a heterologous system that is expanding
      network biology knowledge via in vivo investigations of binary protein-protein
      interactions. Traditionally, the Y2H protocol entails the mating or co
      transformation of yeast in solid agar media followed by visual analysis for
      diploid selection. Having played a key role in identifying protein-protein
      interactions for nearly three decades in a wide range of biological systems, the
      Y2H system assays the interaction between two proteins of interest which results
      in a reconstituted and/or activation of transcription factor allowing a reporter
      gene to be transcribed. Overall, the Y2H method takes advantage of two factors:
      (1) the auxotrophic yeast requires expression of the reporter gene to grow in
      media purposefully designed to lack one or more essential amino acids, and (2)
      the DNA-binding (DB) domain of transcription factor GAL4 is unable to initiate
      transcription unless it is physically associated with an activating domain (AD),
      which, together, DBs and ADs are fused to proteins of interest that must interact
      with each other to reconstitute the transcription factor and activate the
      reporter gene. The applications of Y2H are broad, entailing fields such as drug
      discovery, clinical trials for human disease including cancer and
      neurodegenerative disease, and extend even into synthetic biology applications
      and cellular engineering. This chapter begins with an introduction to the
      fundamental mechanics of Y2H utilizing a genetically engineered strain of yeast
      and proceeds with an in-depth look at the different types of Y2H and turn our
      focus particularly to the GAL4-based Y2H system to map protein-protein
      interactions. We will then provide a step-by-step protocol for the Y2H
      experimentation preceded by a materials listing while simultaneously including
      key notes throughout the entire experimental process of biological-mechanistic
      and historical understandings of the steps.

PMID- 28439867
TI  - Mapping Protein-Protein Interactions Using Affinity Purification and Mass
      Spectrometry.
AB  - The mapping of protein-protein interaction (PPI) networks and their dynamics are
      crucial steps to deciphering the function of a protein and its role in cellular
      pathways, making it critical to have comprehensive knowledge of a protein's
      interactome. Advances in affinity purification and mass spectrometry technology
      (AP-MS) have provided a powerful and unbiased method to capture higher-order
      protein complexes and decipher dynamic PPIs. However, the unbiased calling of
      nonspecific interactions and the ability to detect transient interactions remains
      challenging when using AP-MS, thereby hampering the detection of biologically
      meaningful complexes. Additionally, there are plant-specific challenges with AP
      MS, such as a lack of protein-specific antibodies, which must be overcome to
      successfully identify PPIs. Here we discuss and describe a protocol designed to
      bypass the traditional challenges of AP-MS and provide a roadmap to identify bona
      fide PPIs in plants.

PMID- 28439868
TI  - Measuring Protein Movement, Oligomerization State, and Protein-Protein
      Interaction in Arabidopsis Roots Using Scanning Fluorescence Correlation
      Spectroscopy (Scanning FCS).
AB  - Scanning fluorescence correlation spectroscopy (scanning FCS) can be used to
      determine protein movement, oligomerization state, and protein-protein
      interaction. Here, we describe how to use the scanning FCS techniques of raster
      image correlation spectroscopy (RICS) and pair correlation function (pCF) to
      determine the rate and direction of protein movement. In addition, we detail how
      number and brightness (N&B) and cross-correlation analyses can be used to
      determine oligomerization state and binding ratios of protein complexes. We
      specifically describe how to acquire suitable images for scanning FCS analysis
      using the model plant Arabidopsis and how to perform the various analyses using
      the SimFCS software.

PMID- 28439869
TI  - Studying Protein-Protein Interactions In Planta Using Advanced Fluorescence
      Microscopy.
AB  - The formation of protein complexes through direct protein-protein interaction is
      essential for virtually every biological process, and accordingly the ability to
      determine the interaction properties of specific proteins is important to
      understand these processes. Forster resonance energy transfer (FRET) measurements
      are state-of-the-art confocal fluorescence microscopy- and imaging-based
      techniques that allow the analysis of protein interactions in vivo and in planta,
      in specific compartments of single cells or tissues. Here we provide a step-by
      step guide to perform FRET measurements by acceptor photobleaching (APB) and
      fluorescence lifetime imaging microscopy (FLIM) in the plant expression system
      Nicotiana benthamiana.

PMID- 28439870
TI  - Chemiluminescence-Based Detection of Peptide Activity and Peptide-Receptor
      Binding in Plants.
AB  - In living organisms, physical interaction of ligand molecules with their cognate
      receptors is an indispensable requirement for the initiation of cellular
      signaling pathways. To technically prove the biochemical interaction of ligands
      with their corresponding receptor, a biologically active but labeled peptide is
      required. Easily scorable bioassays, such as the production of reactive oxygen
      species, can be used to quantify the activity of a peptide. By using
      chemiluminescent probes, such as acridinium esters, as conjugates to label
      peptide ligands of interest, quantitative measurements of ligand-receptor binding
      can be performed in standard luminometers. Here we describe how this binding
      approach can be used to reveal peptide ligand-receptor binding in plant material.

PMID- 28439871
TI  - Application of Chemical Genomics to Plant-Bacteria Communication: A High
      Throughput System to Identify Novel Molecules Modulating the Induction of
      Bacterial Virulence Genes by Plant Signals.
AB  - The life cycle of bacterial phytopathogens consists of a benign epiphytic phase,
      during which the bacteria grow in the soil or on the plant surface, and a
      virulent endophytic phase involving the penetration of host defenses and the
      colonization of plant tissues. Innovative strategies are urgently required to
      integrate copper treatments that control the epiphytic phase with complementary
      tools that control the virulent endophytic phase, thus reducing the quantity of
      chemicals applied to economically and ecologically acceptable levels. Such
      strategies include targeted treatments that weaken bacterial pathogens,
      particularly those inhibiting early infection steps rather than tackling
      established infections. This chapter describes a reporter gene-based chemical
      genomic high-throughput screen for the induction of bacterial virulence by plant
      molecules. Specifically, we describe a chemical genomic screening method to
      identify agonist and antagonist molecules for the induction of targeted bacterial
      virulence genes by plant extracts, focusing on the experimental controls required
      to avoid false positives and thus ensuring the results are reliable and
      reproducible.

PMID- 28439872
TI  - Are non-muscle actin isoforms functionally equivalent?
AB  - Actin is highly conserved and it is the most widespread protein in eukaryotic
      cells. One of the most important features of actin, which allows it to have many
      different functions, is its ability to polymerize and interact with many other
      proteins. Actins are the major constituent of the actin cytoskeleton, which is an
      important system that is involved in various aspects of cell function, including
      cell motility, structure, integrity, regulation of signal transduction and
      transcription. Six mammal actin isoforms are highly conserved and share common
      functions. Two of them, beta and gamma non-muscle actin isoforms, which differ
      only by four amino acids located at the N-terminus of the polypeptide chain, are
      required for survival and proper cell functioning. We also summarized data about
      actbl2, which is suggested to be a newly discovered isoactin. Here, we review the
      current knowledge about tissue-specific expression of the non-muscle actin
      isoforms and possible functional differences between them. We also discuss
      molecular tools, which in recent years have allowed for a better understanding of
      the role of these proteins in cell functioning.

PMID- 28439873
TI  - Gender Development in Transgender Preschool Children.
AB  - An increasing number of transgender children-those who express a gender identity
      that is "opposite" their natal sex-are socially transitioning, or presenting as
      their gender identity in everyday life. This study asks whether these children
      differ from gender-typical peers on basic gender development tasks. Three- to 5
      year-old socially transitioned transgender children (n = 36) did not differ from
      controls matched on age and expressed gender (n = 36), or siblings of transgender
      and gender nonconforming children (n = 24) on gender preference, behavior, and
      belief measures. However, transgender children were less likely than both control
      groups to believe that their gender at birth matches their current gender,
      whereas both transgender children and siblings were less likely than controls to
      believe that other people's gender is stable.

PMID- 28439874
TI  - The effective introduction of Lifebox pulse oximetry to Malawi.

PMID- 28439875
TI  - Epigenetic repression of miR-375 is the dominant mechanism for constitutive
      activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.
AB  - Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM).
      However, we recently showed that the serine/threonine kinase PDPK1 and its
      substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play
      pivotal roles in myeloma pathophysiology. In this study, we assessed involvement
      of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of
      plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined
      significance and 73 MM patients showed a significant decrease in miR-375
      expression in patient-derived plasma cells regardless of the clinical stage,
      compared to normal plasma cells. Introduction of miR-375 reduced PDPK1 expression
      in human myeloma cell lines (HMCLs), indicating that miR-375 is the dominant
      regulator of PDPK1 expression. In addition, miR-375 introduction also
      downregulated IGF1R and JAK2 in HMCLs. CpG islands in the MIR375 promoter were
      pathologically hypermethylated in all 8 HMCLs examined and in most of 58 patient
      derived myeloma cells. Treatment with SGI-110, a hypomethylating agent, and/or
      trichostatin A, a histone deacetylase inhibitor, increased miR-375 expression,
      but repressed PDPK1, IGF1R and JAK2 in HMCLs. Collectively, these results show
      the universal involvement of overlapping epigenetic dysregulation for abnormal
      miR-375 repression in MM, which is likely to contribute to myelomagenesis and to
      subsequent myeloma progression by activating oncogenic signalling pathways.

PMID- 28439876
TI  - Functional vision and cognition in infants with congenital disorders of the
      peripheral visual system.
AB  - AIM: To investigate how vision relates to early development by studying vision
      and cognition in a national cohort of 1-year-old infants with congenital
      disorders of the peripheral visual system and visual impairment. METHOD: This was
      a cross-sectional observational investigation of a nationally recruited cohort of
      infants with 'simple' and 'complex' congenital disorders of the peripheral visual
      system. Entry age was 8 to 16 months. Vision level (Near Detection Scale) and non
      verbal cognition (sensorimotor understanding, Reynell Zinkin Scales) were
      assessed. Parents completed demographic questionnaires. RESULTS: Of 90 infants
      (49 males, 41 females; mean 13mo, standard deviation [SD] 2.5mo; range 7-17mo);
      25 (28%) had profound visual impairment (light perception at best) and 65 (72%)
      had severe visual impairment (basic 'form' vision). The Near Detection Scale
      correlated significantly with sensorimotor understanding developmental quotients
      in the 'total', 'simple', and 'complex' groups (all p<0.001). Age and vision
      accounted for 48% of sensorimotor understanding variance. Infants with profound
      visual impairment, especially in the 'complex' group with congenital disorders of
      the peripheral visual system with known brain involvement, showed the greatest
      cognitive delay. INTERPRETATION: Lack of vision is associated with delayed early
      object manipulative abilities and concepts; 'form' vision appeared to support
      early developmental advance. This paper provides baseline characteristics for
      cross-sectional and longitudinal follow-up investigations in progress. A
      methodological strength of the study was the representativeness of the cohort
      according to national epidemiological and population census data.

PMID- 28439877
TI  - Increased non-relapse mortality due to high-dose cytarabine plus CY/TBI in
      BMT/PBSCT for acute lymphoblastic leukaemia in adults.
AB  - The efficacy of high-dose cytarabine (HDCA) plus cyclophosphamide/total-body
      irradiation (CY/TBI) has been proved in cord blood transplantation (CBT) for
      acute lymphoblastic leukaemia (ALL), but not in bone marrow or peripheral blood
      stem cell transplantation (BMT/PBSCT). In this cohort study, we compared the
      prognosis of CY/TBI (N = 1244) and HDCA/CY/TBI (N = 316) regimens in BMT/PBSCT
      for ALL. The addition of HDCA decreased post-transplant relapse, while
      significantly increasing non-relapse mortality (risk ratio, 1.33), and overall
      survival was not improved. The positive effects of HDCA reported in CBT cannot be
      extrapolated to BMT/PBSCT, and HDCA may not be recommended in these procedures.

PMID- 28439879
TI  - Leucocyte and eosinophil counts predict progression-free survival in relapsed or
      refractory classical Hodgkin Lymphoma patients treated with PD1 inhibition.

PMID- 28439880
TI  - Heavy/light chain ratio for the assessment of minimal residual disease in myeloma
      patients achieving complete response.

PMID- 28439878
TI  - Dissecting and modeling the emergent murine TEC compartment during ontogeny.
AB  - The origin of the thymic epithelium, i.e. the cortical (cTEC) and medullary
      (mTEC) epithelial cells, from bipotent stem cells through TEC progenitors and
      lineage-specific progeny still remains poorly understood. We sought to obtain an
      unbiased view of the incipient emergence of TEC subsets by following embryonic
      TEC development based on co-expression of EpCAM, CD80 and MHC class II (MHCII) on
      non-hematopoietic (CD45- ) thymic stromal cells in wild-type BL6 mice. Using a
      combination of ex vivo analysis, Re-aggregate Thymic Organ Culture (RTOC)
      reconstitution assays and mathematical modeling, we traced emergent lineage
      commitment in murine embryonic TECs. Both experimental and mathematical datasets
      supported the following developmental sequence: MHCII- CD80- -> MHCIIlo CD80- ->
      MHCIIhi CD80- -> MHCIIhi CD80hi TECs, whereby MHCIIhi CD80- and MHCIIhi CD80hi
      TECs bear features of cTECs and mTECs respectively. These emergent MHCIIhi CD80-
      cTECs directly generate mature MHCIIhi CD80hi mTECs in vivo and in vitro, thus
      supporting the asynchronous model of TEC lineage commitment.

PMID- 28439881
TI  - Effect of cocoa on blood pressure.
AB  - BACKGROUND: High blood pressure is an important risk factor for cardiovascular
      disease, contributing to about 50% of cardiovascular events worldwide and 37% of
      cardiovascular-related deaths in Western populations. Epidemiological studies
      suggest that cocoa-rich products reduce the risk of cardiovascular disease.
      Flavanols found in cocoa have been shown to increase the formation of endothelial
      nitric oxide which promotes vasodilation and therefore blood pressure reduction.
      Here we update previous meta-analyses on the effect of cocoa on blood pressure.
      OBJECTIVES: To assess the effects on blood pressure of chocolate or cocoa
      products versus low-flavanol products or placebo in adults with or without
      hypertension when consumed for two weeks or longer. SEARCH METHODS: This is an
      updated version of the review initially published in 2012. In this updated
      version, we searched the following electronic databases from inception to
      November 2016: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE
      and Embase. We also searched international trial registries, and the reference
      lists of review articles and included trials. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) investigating the effects of chocolate or cocoa products
      on systolic and diastolic blood pressure in adults for a minimum of two weeks
      duration. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data and assessed the risks of bias in each trial. We conducted random
      effects meta-analyses on the included studies using Review Manager 5. We explored
      heterogeneity with subgroup analyses by baseline blood pressure, flavanol content
      of control group, blinding, age and duration. Sensitivity analyses explored the
      influence of unusual study design. MAIN RESULTS: Thirty-five trials (including 40
      treatment comparisons) met the inclusion criteria. Of these, we added 17 trials
      (20 treatment comparisons) to the 18 trials (20 treatment comparisons) in the
      previous version of this updated review.Trials provided participants with 30 to
      1218 mg of flavanols (mean = 670 mg) in 1.4 to 105 grams of cocoa products per
      day in the active intervention group. The control group received either a
      flavanol-free product (n = 26 treatment comparisons) or a low-flavanol-containing
      cocoa powder (range 6.4 to 88 mg flavanols (mean = 55 mg, 13 treatment
      comparisons; 259 mg, 1 trial).Meta-analyses of the 40 treatment comparisons
      involving 1804 mainly healthy participants revealed a small but statistically
      significant blood pressure-reducing effect of flavanol-rich cocoa products
      compared with control in trials of two to 18 weeks duration (mean nine
      weeks):Mean difference systolic blood pressure (SBP) (95% confidence interval
      (CI): -1.76 (-3.09 to -0.43) mmHg, P = 0.009, n = 40 treatment comparisons, 1804
      participants;Mean difference diastolic blood pressure (DBP) (95% CI): -1.76 (
      2.57 to -0.94) mmHg, P < 0.001, n = 39 treatment comparisons, 1772
      participants.Baseline blood pressure may play a role in the effect of cocoa on
      blood pressure. While systolic blood pressure was reduced significantly by 4 mmHg
      in hypertensive people (n = 9 treatment comparisons, 401 participants), and
      tended to be lowered in prehypertensive people (n= 8 treatment comparisons, 340
      participants), there was no significant difference in normotensive people (n = 23
      treatment comparisons, 1063 participants); however, the test for subgroup
      differences was of borderline significance (P = 0.08; I2 = 60%), requiring
      further research to confirm the findings.Subgroup meta-analysis by blinding
      suggested a trend towards greater blood pressure reduction in unblinded trials
      compared to double-blinded trials, albeit statistically not significant. Further
      research is needed to confirm whether participant expectation may influence blood
      pressure results. Subgroup analysis by type of control (flavanol-free versus low
      flavanol control) did not reveal a significant difference.Whether the age of
      participants plays a role in the effect of cocoa on blood pressure, with younger
      participants responding with greater blood pressure reduction, needs to be
      further investigated.Sensitivity analysis excluding trials with authors employed
      by trials sponsoring industry (33 trials, 1482 participants) revealed a small
      reduction in effect size, indicating some reporting bias.Due to the remaining
      heterogeneity, which we could not explain in terms of blinding, flavanol content
      of the control groups, age of participants, or study duration, we downgraded the
      quality of the evidence from high to moderate.Results of subgroup analyses should
      be interpreted with caution and need to be confirmed or refuted in trials using
      direct randomised comparisons.Generally, cocoa products were highly tolerable,
      with adverse effects including gastrointestinal complaints and nausea being
      reported by 1% of participants in the active cocoa intervention group and 0.4% of
      participants in the control groups (moderate-quality evidence). AUTHORS'
      CONCLUSIONS: This review provides moderate-quality evidence that flavanol-rich
      chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering
      effect in mainly healthy adults in the short term.These findings are limited by
      the heterogeneity between trials, which could not be explained by prespecified
      subgroup analyses, including blinding, flavanol content of the control groups,
      age of participants, or study duration. However, baseline blood pressure may play
      a role in the effect of cocoa on blood pressure; subgroup analysis of trials with
      (pre)hypertensive participants revealed a greater blood pressure-reducing effect
      of cocoa compared to normotensive participants with borderline significance.Long
      term trials investigating the effect of cocoa on clinical outcomes are also
      needed to assess whether cocoa has an effect on cardiovascular events and to
      assess potential adverse effects associated with chronic ingestion of cocoa
      products.

PMID- 28439882
TI  - Prevalence and clinical relevance of thyroid stimulating hormone receptor
      blocking antibodies in autoimmune thyroid disease.
AB  - The prevalence and clinical relevance of thyroid stimulating hormone (TSH)
      receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid
      disease (AITD) was investigated. Serum TBAb were measured with a reporter gene
      bioassay using Chinese hamster ovary cells. Blocking activity was defined as
      percentage inhibition of luciferase expression relative to induction with bovine
      TSH alone (cut-off 40% inhibition). All samples were measured for TSHR
      stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A
      total of 1079 unselected, consecutive patients with AITD and 302 healthy controls
      were included. All unselected controls were negative for TBAb and TSAb. In
      contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis
      and Graves' disease was 67 of 722 (9.3%) and 15 of 357 (4.2%). Of the 82 TBAb
      positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid,
      euthyroid and hyperthyroid, respectively. Ten patients were both TBAb- and TSAb
      positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid
      associated orbitopathy was present in four of 82 (4.9%) TBAb-positive patients,
      with dual TSHR antibody positivity being observed in three. TBAb correlated
      positively with TBII (r = 0.67, P < 0.001) and negatively with TSAb (r = -0.86, P
      < 0.05). The percentage of TBII-positive patients was higher the higher the level
      of inhibition in the TBAb assay. Of the TBAb-positive samples with  > 70%
      inhibition, 87% were TBII-positive. Functional TSHR antibodies impact thyroid
      status. TBAb determination is helpful in the evaluation and management of
      patients with AITD. The TBAb assay is a relevant and important tool to identify
      potentially reversible hypothyroidism.

PMID- 28439884
TI  - The Home Environment Shapes Emotional Eating.
AB  - Emotional overeating (EOE) is the tendency to eat more in response to negative
      emotions; its etiology in early life is unknown. We established the relative
      genetic and environmental influences on EOE in toddlerhood and early childhood.
      Data were from Gemini, a population-based cohort of 2,402 British twins born in
      2007. EOE was measured using the "emotional overeating" scale of the Child Eating
      Behavior Questionnaire (CEBQ) at 16 months and 5 years. A longitudinal
      quantitative genetic model established that genetic influences on EOE were
      minimal; on the other hand, shared environmental influences explained most of the
      variance. EOE was moderately stable from 16 months to 5 years and continuing
      environmental factors shared by twin pairs at both ages explained the
      longitudinal association.

PMID- 28439883
TI  - An update for Richter syndrome - new directions and developments.
AB  - High-grade transformation of chronic lymphocytic leukaemia [Richter syndrome
      (RS)] is rare and represents a unique and uncommon clinical challenge. Clonally
      related diffuse large B cell type RS is a chemotherapy-resistant and devastating
      disease. Patients are typically elderly, immunosuppressed and present with a
      rapidly deteriorating performance status. Historical outcomes suggest a median
      overall survival of approximately 8 months. RS remains is an area of high unmet
      clinical need. The molecular profile and treatment needs of patients are likely
      to change over time with the advent of novel B cell receptor inhibitors,
      monoclonal antibodies and BH3 mimetics. Herein, we summarise what is known
      regarding the molecular drivers of RS and the existing clinical trial data,
      including the recently published CHOP-OR (cyclophosphamide, doxorubicin,
      vincristine, prednisolone and ofatumumab followed by ofatumumab maintenance in
      newly diagnosed RS) trial. We discuss novel agents in development with a focus on
      the second-generation Bruton tyrosine kinase inhibitor acalabrutinib, checkpoint
      inhibition and the potential role of precision medicine in future trials of RS.

PMID- 28439885
TI  - A novel GFI1B mutation at the first zinc finger domain causes congenital
      macrothrombocytopenia.

PMID- 28439886
TI  - Lifebox pulse oximeter implementation in Malawi: evaluation of educational
      outcomes and impact on oxygen desaturation episodes during anaesthesia.
AB  - Pulse oximetry is an essential monitor for safe anaesthesia but is often not
      available in low-income countries. The aim of this study was to determine whether
      the introduction of pulse oximetry with training was feasible and could reduce
      the incidence of oxygen desaturation during anaesthesia in a low-income country.
      Pulse oximeters were donated, with training, to 83 non-physician anaesthetists in
      Malawi. Knowledge was tested immediately before and after training and at follow
      up. Providers were asked to record the lowest peripheral oxygen saturation (SpO2
      ) for the first 100 cases anaesthetised after training. The primary clinical
      outcome was the proportion of cases with an oxygen desaturation event (SpO2 <
      90%). Seventy-seven of 83 (93%) participants completed all pre- and post-training
      tests. Pulse oximetry knowledge improved after training from a median (IQR
      [range]) score of 39 (37-42 [28-48]) to 44 (42-46 [35-50]) and this knowledge was
      maintained for 8 months (p < 0.001). Oxygen saturation data and provider
      responses were recorded for 4772 cases. The proportion of oxygen desaturation
      episodes decreased from 17.2% to 6.5%, representing a 36% reduction in the odds
      of an oxygen desaturation event in the second 50 cases compared with the first 50
      (OR 0.64, 95%CI 0.50-0.82, p < 0.001). We conclude that donation of pulse
      oximeters, with training, in Malawi was feasible, improved knowledge and reduced
      the incidence of oxygen desaturation events.

PMID- 28439888
TI  - Emotional Feeding and Emotional Eating: Reciprocal Processes and the Influence of
      Negative Affectivity.
AB  - Emotional eating, that is, eating more in response to negative mood, is often
      seen in children. But the origins of emotional eating remain unclear. In a
      representative community sample of Norwegian 4-year-olds followed up at ages 6,
      8, and 10 years (analysis sample: n = 801), one potential developmental pathway
      was examined: a reciprocal relation between parental emotional feeding and child
      emotional eating. The results revealed that higher levels of emotional feeding
      predicted higher levels of emotional eating and vice versa, adjusting for body
      mass index and initial levels of feeding and eating. Higher levels of
      temperamental negative affectivity (at age 4) increased the risk for future
      emotional eating and feeding.

PMID- 28439887
TI  - Clinical significance of recurrent copy number aberrations in B-lineage acute
      lymphoblastic leukaemia without recurrent fusion genes across age cohorts.
AB  - Copy number aberrations (CNAs) represent cooperating events in B-lineage acute
      lymphoblastic leukaemia (B-ALL); however, their clinical relevance across
      different age cohorts is unclear. We analysed the recurrent CNAs in 157 age
      stratified B-ALL negative cases for recurrent rearrangements (B-NEG ALL), and
      their association with patients' clinico-biological features. We found that: (i)
      CDKN2A/RB1-deleted and EBF1-deleted adults had a shorter disease-free survival
      than those with wild-type, (ii) among the unfavourable markers, CDKN2A/RB1
      deletions and K/NRAS mutations retained their impact in multivariate analysis,
      encouraging the evaluation of CDKN2A/RB1 deletions and RAS mutations in the
      diagnostic/prognostic workflow to refine ALL risk assessment.

PMID- 28439889
TI  - Prevalence and characteristics of autism spectrum disorders in children with
      cerebral palsy.
AB  - AIM: To evaluate the prevalence of co-occurring autism spectrum disorders (ASDs)
      among children with cerebral palsy (CP), and to describe their characteristics.
      METHOD: The data of 1225 CP cases from four population-based registers (Iceland,
      Sweden, and two in France) and one population-based surveillance programme (North
      East England, UK) participating in the Surveillance of Cerebral Palsy in Europe
      Network (SCPE) were analysed. The ASD diagnoses were systematically recorded
      using category F84 of the International Classification of Diseases, 10th
      Revision. The registers provided data on children born between 1995 and 2006,
      while the cross-sectional survey in the UK concerned children aged 0 to 19 years,
      registered in 2010. RESULTS: Among the children with CP, 107 had an associated
      diagnosis of ASD - i.e., 8.7% of the study population (95% confidence interval
      7.2-10.5). This proportion varied across centres from 4.0% to 16.7% but was
      independent of CP prevalence. Male sex, co-occurring epilepsy, intellectual
      disability, and better walking ability were associated with the coexistence of
      ASD. INTERPRETATION: Our findings support the need for a multidisciplinary
      approach to management of children with CP to adequately identify and address all
      facets of presentation, including ASD.

PMID- 28439890
TI  - Herpes simplex virus-induced anti-N-methyl-d-aspartate receptor encephalitis: a
      systematic literature review with analysis of 43 cases.
AB  - AIM: To conduct a systematic literature review on patients with biphasic disease
      with herpes simplex virus (HSV) encephalitis followed by anti-N-methyl-D
      aspartate receptor (NMDAR) encephalitis. METHOD: We conducted a case report and
      systematic literature review (up to 10 December 2016), focused on differences
      between herpes simplex encephalitis (HSE) and anti-NMDAR encephalitis phases, age
      related characteristics of HSV-induced anti-NMDAR encephalitis, and therapy. For
      statistical analyses, McNemar's test, Fisher's test, and Wilcoxon rank sum test
      were used (two-tailed significance level set at 5%). RESULTS: Forty-three
      patients with biphasic disease were identified (31 children). Latency between HSE
      and anti-NMDAR encephalitis was significantly shorter in children than adults
      (median 24 vs 40.5d; p=0.006). Compared with HSE, anti-NMDAR encephalitis was
      characterized by significantly higher frequency of movement disorder (2.5% vs 75%
      respectively; p<0.001), and significantly lower rate of seizures (70% vs 30%
      respectively; p=0.001). Compared with adults, during anti-NMDAR encephalitis
      children had significantly more movement disorders (86.7% children vs 40% adults;
      p=0.006), fewer psychiatric symptoms (41.9% children vs 90.0% adults; p=0.025),
      and a slightly higher median modified Rankin Scale score (5 in children vs 4 in
      adults; p=0.015). During anti-NMDAR encephalitis, 84.6 per cent of patients
      received aciclovir (for <=7d in 22.7%; long-term antivirals in 18.0% only), and
      92.7 per cent immune therapy, but none had recurrence of HSE clinically or using
      cerebrospinal fluid HSV polymerase chain reaction (median follow-up 7mo).
      INTERPRETATION: Our review suggests that movement disorder may help differentiate
      clinically an episode of HSV-induced anti-NMDAR encephalitis from HSE relapse.
      Compared with adults, children have shorter latency between HSE and anti-NMDAR
      encephalitis and, during anti-NMDAR encephalitis, more movement disorder, fewer
      psychiatric symptoms, and slightly more severe disease. According to our results,
      immune therapy given for HSV-induced anti-NMDAR encephalitis does not predispose
      patients to HSE recurrence.

PMID- 28439891
TI  - The new era of chelation treatments: effectiveness and safety of 10 different
      regimens for controlling iron overloading in thalassaemia major.
AB  - This review outlines the effectiveness and safety of 10 different regimens for
      controlling iron overloading in thalassaemia major (TM). For each treatment, the
      strength of the evidence was documented according to the guidelines of the
      American College of Cardiology and the American Heart Association. Serum ferritin
      (SF), liver iron concentration (LIC), heart T2* signal, heart damage and survival
      were used to assess effectiveness. Five chelation regimens out of 10 showed Level
      A Evidence in controlling iron overloading, as determined by SF levels and LIC.
      Three out of 10 chelation regimens were able to control heart iron levels, as
      determined by T2* signals with Level A Evidence. Two chelation regimens were able
      to improve/reverse heart damage and four increased of survival with Level B
      Evidence. These advances mean that the current survival of TM patients is now
      similar to that of thalassaemia intermedia patients.

PMID- 28439892
TI  - Cerebrospinal fluid cyto-/chemokine profile during acute herpes simplex virus
      induced anti-N-methyl-d-aspartate receptor encephalitis and in chronic
      neurological sequelae.
AB  - AIM: To examine the cytokine/chemokine profile of cerebrospinal fluid (CSF)
      during acute herpes simplex virus-induced N-methyl-d-aspartate receptor (NMDAR)
      autoimmunity and in chronic/relapsing post-herpes simplex virus encephalitis
      (HSE) neurological syndromes. METHOD: We measured longitudinal serial CSF cyto
      /chemokines (n=34) and a glial marker (calcium-binding astroglial protein, S100B)
      in one patient during acute HSE and subsequent anti-NMDAR encephalitis, and
      compared the results with those from two patients with anti-NMDAR encephalitis
      without preceding HSE. We also compared cyto-/chemokines in cross-sectional CSF
      samples from three children with previous HSE who had ongoing chronic or
      relapsing neurological symptoms (2yr 9 mo-16y after HSE) with those in a group of
      children having non-inflammatory neurological conditions (n=20). RESULTS: Acute
      HSE showed elevation of a broad range of all T-helper-subset-related cyto
      /chemokines and S100B whereas the post-HSE anti-NMDAR encephalitis phase showed
      persistent elevation of two of five T-helper-1 (chemokine [C-X-C motif] ligand 9
      [CXCL9], CXCL10), three of five predominantly B-cell (CXCL13, CCL19, a
      proliferation-inducing ligand [APRIL])-mediated cyto-/chemokines, and interferon
      alpha. The post-HSE anti-NMDAR encephalitis inflammatory response was more
      pronounced than anti-NMDAR encephalitis. All three chronic post-HSE cases showed
      persistent elevation of CXCL9, CXCL10, and interferon-alpha, and there was
      histopathological evidence of chronic lymphocytic inflammation in one biopsied
      case 7 years after HSE. Two of three chronic cases showed a modest response to
      immune therapy. INTERPRETATION: HSE-induced anti-NMDAR encephalitis is a complex
      and pronounced inflammatory syndrome. There is persistent CSF upregulation of
      cyto-/chemokines in chronic or relapsing post-HSE neurological symptoms, which
      may be modifiable with immune therapy. The elevated cyto-/chemokines may be
      targets of monoclonal therapies.

PMID- 28439894
TI  - Dengue fever rash: white islands in a sea of red.

PMID- 28439893
TI  - Outcome after intensive reinduction therapy and allogeneic stem cell transplant
      in paediatric relapsed acute myeloid leukaemia.
AB  - Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after
      primary therapy it is important to define prognostic factors and identify optimal
      therapy. From 1993 to 2012, 543 children from the Nordic countries were treated
      according to two consecutive protocols: 208 children relapsed. The influence of
      disease characteristics, first line treatment, relapse therapy and duration of
      first remission on outcome was analysed. Second complete remission (CR2) was
      achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y ) was 39
      +/- 4% for the whole group and 43 +/- 4% for the 190 patients given re-induction
      therapy, of whom 76% received regimens that included fludarabine, cytarabine
      (FLA) +/- anthracyclines, 18% received Nordic Society for Paediatric Haematology
      and Oncology (NOPHO) upfront blocks and 5% received other regimens. Late relapse
      >=1 year from diagnosis, no allogeneic stem cell transplantation (SCT) in first
      remission and core binding factor AML were independent favourable prognostic
      factors for survival. For the 128 children (124 in CR2) that received SCT as
      consolidation therapy after relapse, OS5y was 61 +/- 5%. Four of 19 children
      (21%) survived without receiving SCT as part of relapse therapy. Our data show
      that intensive re-induction followed by SCT can give cure rates of 40% in
      children with relapsed AML.

PMID- 28439895
TI  - Intravascular large B-cell lymphoma presenting as a pituitary mass with bilateral
      adrenal enlargement and haemophagocytic lymphohistiocytosis.

PMID- 28439896
TI  - Topical corticosteroid phobia in atopic dermatitis: International feasibility
      study of the TOPICOP score.
AB  - BACKGROUND: Adherence to topical corticosteroids (TCS) is essential for the
      effective treatment of atopic dermatitis but can be limited by concerns about
      their use. This study examined the feasibility of applying the validated TOPICOP
      score for assessing TCS phobia across different countries. METHODS: This was a
      prospective multicentre feasibility study conducted in 21 hospitals in 17
      countries. Patients >3 months of age with atopic dermatitis or their parents or
      legal representatives completed a validated translation of the TOPICOP
      questionnaire in the country's native language. Respondents also completed
      questionnaires collecting opinions about the feasibility and acceptability of the
      TOPICOP questionnaire. RESULTS: A total of 1564 participants in 15 countries were
      included in the analysis. 81% of respondents considered the questions clear or
      very clear, and 79% reported that it took less than 5 minutes to complete. Each
      of the individual items in the TOPICOP questionnaire was considered to be not at
      all difficult to answer by 49% to 74% of participants. The mean global TOPICOP
      score was 44.7%+/-20.5. Mean TOPICOP subscores were 37.0+/-22.8% for knowledge
      and beliefs, 54.7+/-27.8% for fears and 50.1+/-29.1% for behaviours. Global
      scores and subscores differed between countries, although the subscores did not
      always vary in parallel, suggesting different levels of TCS phobia and different
      drivers for each country. CONCLUSIONS: The TOPICOP score can be feasibly applied
      across countries and may therefore be useful for obtaining qualitative and
      quantitative data from international studies and for adapting patient education
      and treatment.

PMID- 28439897
TI  - Platelet lysate obtained via plateletpheresis performed in standing and awake
      equine donors.
AB  - BACKGROUND: Platelet preparations containing growth factors, attachment factors,
      and enzymes are appealing to enhance healing of injured tissues and as an
      alternative to xenogenic serum in cell culture media. Plateletpheresis is
      commonly used to collect platelets in human medicine but has not been validated
      in horses. STUDY DESIGN AND METHODS: Plateletpheresis to collect platelet
      concentrate was performed on six female, mixed breed, chemically restrained
      horses using commercially available apheresis equipment. Before and immediately
      after plateletpheresis, we performed physical examinations and collected blood
      for chemistry and coagulation panels and then again at 8, 16, 24, and 48 hours
      after the procedure. To produce platelet lysate, the platelet concentrate
      underwent two freeze-thaw cycles followed by centrifugation and filtration
      processing. The platelet lysate was then analyzed for cellular debris,
      fibrinogen, and growth factors. RESULTS: The collected platelet concentration
      contained a mean platelet yield of 390 * 103 /MUL. Donor platelet count decreased
      from a mean of 193 * 103 /MUL to 138 * 103 /MUL after plateletpheresis, but no
      individual was at risk for hemorrhage. Pooled platelet lysate had minimal
      cellular residue and contained growth factor concentrations at 6.1 ng/mL for
      transforming growth factor-beta1, at 3.5 ng/mL for platelet-derived growth factor
      BB, and at 13.8 ng/mL for vascular endothelial growth factor-A. CONCLUSION:
      Plateletpheresis using commercially available apheresis equipment is a feasible
      option for collecting platelet concentrate from equine donors. The lysate
      generated from the apheresis product contains growth factors and has potential to
      be used as a fetal bovine serum substitute for cell culture.

PMID- 28439898
TI  - Optimizing autologous nonmobilized mononuclear cell collections for cellular
      therapy in pediatric patients with high-risk leukemia.
AB  - BACKGROUND: The manufacturing of cellular products for immunotherapy, such as
      chimeric antigen receptor T cells, requires successful collection of mononuclear
      cells. Collections from children with high-risk leukemia present a challenge,
      especially because the established COBE Spectra apheresis device is being
      replaced by the novel Spectra Optia device (Optia) in many institutions.
      Published experience for mononuclear cell collections in children with Optia is
      lacking. Our aim was to compare the two collection devices and describe modified
      settings on the Optia to optimize mononuclear cell collections. STUDY DESIGN AND
      METHODS: As a quality initiative, we retrospectively collected and compared data
      from mononuclear cell collections on both devices. Collected data included
      patient's clinical characteristics; collection parameters, including
      precollection lymphocyte/CD3 counts, total blood volumes processed, runtimes, and
      side effects (including complete blood count and electrolyte changes); and
      product characteristics, including volumes and cell counts. Collection
      efficiencies and collection ratios were calculated. RESULTS: Twenty-six
      mononuclear cell collections were performed on 20 pediatric patients: 11 with
      COBE and 15 with Optia. Adequate mononuclear cell products were successfully
      collected with a single procedure from all patients except one, with mean
      calculated mononuclear cell collection efficiency that was significantly higher
      from Optia collections compared with COBE collections (57.9 +/- 4.6% vs 40.3 +/-
      6.2%, respectively; p = 0.04). CD3-positive yields were comparable on both
      machines (p = 0.34) with significantly smaller blood volumes processed on Optia.
      Collected products had larger volumes on Optia. No significant side effects
      attributed to the procedure were noted. CONCLUSION: Mononuclear cell apheresis
      using the Optia device in children is more efficient and is as safe as that with
      the COBE device.

PMID- 28439899
TI  - Parents as Partners: A U.K. Trial of a U.S. Couples-Based Parenting Intervention
      For At-Risk Low-Income Families.
AB  - Despite the well-established links between couple relationship quality and
      healthy family functioning, and burgeoning evidence from the international
      intervention field, there is little or no evidence of the efficacy of couples
      based interventions from the United Kingdom (U.K.). This study explored whether
      the Parents as Partners (PasP) program, a group-based intervention developed in
      the United States, brought about the same benefits in the U.K. The evaluation is
      based on 97 couples with children from communities with high levels of need,
      recruited to PasP because they are at high risk for parent and child
      psychopathology. Both mothers and fathers completed self-report questionnaires
      assessing parents' psychological distress, parenting stress, couple relationship
      quality and conflict, fathers' involvement in child care and, importantly,
      children's adjustment. Multilevel modeling analysis comparing parents' responses
      pre- and postintervention not only showed substantial improvements for both
      parents on multiple measures of couple relationship quality, but also
      improvements in parent and child psychopathology. Analyses also indicated most
      substantial benefits for couples displaying poorest functioning at baseline. The
      findings provide initial evidence for the successful implementation of PasP, an
      American-origin program, in the U.K., and add support for the concept of the
      couple relationship as a resource by which to strengthen families.

PMID- 28439900
TI  - Herpes B virus replication and viral lesions in the liver of a cynomolgus macaque
      which died from severe disease with rapid onset.
AB  - Herpes B virus (BV, Macacine alphaherpesvirus 1) infects macaques
      asymptomatically, with rare exceptions, but can cause fatal encephalitis in
      humans. Here, we report disseminated BV infection in a cynomolgus macaque that
      had died within 12 hour after the onset of unspecific symptoms. Multifocal
      lesions surrounded by viral antigen were detected in liver while other organs
      remained inconspicuous, indicating that the liver is a major target. Moreover,
      high copy numbers of viral DNA were found in feces, underlining the excrements
      are a potential source of transmission.

PMID- 28439901
TI  - Biomimetic strategies to recapitulate organ specific microenvironments for
      studying breast cancer metastasis.
AB  - The progression of breast cancer from the primary tumor setting to the metastatic
      setting is the critical event defining Stage IV disease, no longer considered
      curable. The microenvironment at specific organ sites is known to play a key role
      in influencing the ultimate fate of metastatic cells; yet microenvironmental
      mediated-molecular mechanisms underlying organ specific metastasis in breast
      cancer are not well understood. This review discusses biomimetic strategies
      employed to recapitulate metastatic organ microenvironments, particularly, bone,
      liver, lung and brain to elucidate the mechanisms dictating metastatic breast
      cancer cell homing and colonization. These biomimetic strategies include in vitro
      techniques such as biomaterial-based co-culturing techniques, microfluidics,
      organ-mimetic chips, bioreactor technologies, and decellularized matrices as well
      as cutting edge in vivo techniques to better understand the interactions between
      metastatic breast cancer cells and the stroma at the metastatic site. The
      advantages and disadvantages of these systems are discussed. In addition, how
      creation of biomimetic models will impact breast cancer metastasis research and
      their broad utility is explored.

PMID- 28439902
TI  - Concentrated lyophilized plasma used for reconstitution of whole blood leads to
      higher coagulation factor activity but unchanged thrombin potential compared with
      fresh-frozen plasma.
AB  - BACKGROUND: During massive hemorrhage, it is recommended to transfuse red blood
      cells, platelet concentrate, and fresh-frozen plasma in a ratio close to 1:1:1.
      To avoid the thawing process of fresh frozen plasma, lyophilized plasma (LP) is
      increasingly used. Evidence is limited on the activity of coagulation factors in
      reconstituted blood using LP and concentrated LP versions. STUDY DESIGN AND
      METHODS: Whole blood from ten healthy volunteers was separated into red blood
      cell, fresh frozen plasma, and platelet concentrate units. Aliquots of red blood
      cells and plasma concentrate were mixed with either fresh frozen plasma (200 mL)
      or LP at reconstitution ratios of 2:1:1, 1:1:1, and 1:1:2. LP was used either at
      the recommended standard volume of 200 mL (LP200) or was more concentrated at
      volumes of 100 and 50 mL (LP100 and LP50, respectively). The hemostatic capacity
      of each reconstituted whole blood sample was tested with blood cell counts,
      standard coagulation tests, factor activity, thrombin generation, and
      viscoelastic assays. RESULTS: Hematocrit, platelet counts, and fibrinogen levels
      of the three ratios were similar between FFP200 and LP200 units but were lower
      compared with the corresponding ratios in LP100 and LP50 units. The activity of
      procoagulant and anticoagulant factors increased linearly with the increasing
      plasmatic fraction and, at 1:1:2 ratio, was significantly higher in LP50 units
      compared with FFP200 and LP200 units. Thrombin generation was similar throughout
      the four plasma groups at any ratio. CONCLUSIONS: Decreasing the dilution volume
      of LP facilitates reaching higher hematocrit and coagulation protein levels
      without a relevant increase in thrombin generation. This is due to preserved
      balance between procoagulant and anticoagulant factors in the concentrated LP
      preparations.

PMID- 28439903
TI  - Did Health Care Reform Help Kentucky Address Disparities in Coverage and Access
      to Care among the Poor?
AB  - OBJECTIVE: To evaluate the impact of Kentucky's full rollout of the Affordable
      Care Act on disparities in access to care due to poverty. DATA SOURCE: Restricted
      version of the Behavioral Risk Factor Surveillance System (BRFSS) for Kentucky
      and years 2011-2015. STUDY DESIGN: We use a difference-in-differences framework
      to compare trends before and after implementation of the Affordable Care Act
      (ACA) in health insurance coverage, several access measures, and health care
      utilization for residents in higher versus lower poverty ZIP codes. PRINCIPAL
      FINDINGS: Much of the reduction in Kentucky's uninsured rate appears driven by
      large uptakes in coverage from areas with higher concentrations of poverty.
      Residents in high-poverty communities experienced larger reductions, 8 percentage
      points (pp) in uninsured status and 7.5 pp in reporting unmet needs due to costs,
      than residents of lower poverty areas. These effects helped remove pre-ACA
      disparities in uninsured rates across these areas. CONCLUSION: Because we observe
      positive effects on coverage and reductions in financial barriers to care among
      those from poorer communities, our findings suggest that expanding Medicaid helps
      address the health care needs of the impoverished.

PMID- 28439904
TI  - Adaptation and validation of the oral health literacy instrument for the Chilean
      population.
AB  - OBJECTIVE: To report the adaptation and cultural validation of the Oral Health
      Literacy Instrument (OHLI) for the adult Chilean population attending public and
      university health services. STUDY DESIGN: The original OHLI in English was
      translated to Spanish and back-translated, then a preliminary version was
      obtained following review by four experts. A pilot study was carried out in 30
      patients, who were asked to assess their understanding of the questionnaire. The
      following variables were included: sociodemographic factors (sex, age, average
      monthly income, education and marital status); oral health (history of caries,
      periodontal disease and oral hygiene); oral health-related quality of life;
      health literacy; oral health literacy; and psychometric properties (internal
      consistency, temporal stability, convergent validity and predictive validity).
      Clinical examination and questionnaire administration were carried out at the
      public health centres where the participants were receiving treatment. RESULTS: A
      total of 482 persons participated in the study. The internal consistency was
      high; Cronbach's alpha values were 0.864 for the first section, 0.739 for the
      second section and 0.887 for the entire instrument. The temporal stability was
      good, and the intraclass correlation coefficient was >0.6. Regarding convergent
      validity, the correlation of Chilean version of OHLI (OHLI-cl) with health
      literacy was positively moderate to strong (r > 0.5 and rho > 0.5) and
      statistically significant (P < 0.01). Regarding predictive validity, the
      correlation of OHLI with oral health damage was negatively weak to moderate (r < 
      0.2 and rho < -0.2) and statistically significant (P < 0.01). CONCLUSION: The
      OHLI-cl demonstrates adequate psychometric properties for measuring the oral
      health literacy in Chilean populations attending public and university health
      services.

PMID- 28439905
TI  - Der f 35: An MD-2-like house dust mite allergen that cross-reacts with Der f 2
      and Pso o 2.
AB  - BACKGROUND: Dermatophagoides farinae is a source of airborne house dust mite
      (HDM) allergens. We elucidated IgE-reactive allergens from D. farinae by two
      dimensional immunoblotting-based allergenome analysis, and identified one new
      allergen, named Der f 35, that possesses IgE-binding capacity comparable to that
      of Der f 2. The aim of this study was to clarify the allergenic capacity of new
      HDM allergen Der f 35. METHODS: We cloned der f 35 from D. farinae mRNA and
      produced recombinant Der f 35 in Escherichia coli. The IgE-binding capacity of
      Der f 35 and its cross-reactivity with group 2 allergens from D. farinae and
      Psoroptes ovis were determined by enzyme-linked immunosorbent assay (ELISA) and
      ELISA inhibition assays, respectively. RESULTS: The deduced amino acid sequence
      for der f 35, which possesses the MD-2-related lipid-recognition domain, showed
      higher identity with group 2 allergens from P. ovis (61.5%) and Blomia tropicalis
      (50.7%) than with Der f 2 (40.8%). Der f 35 showed IgE-binding frequencies of
      77.5% (31/40) for the native form upon allergenome analysis and 51.4% (18/35) for
      recombinant structure by ELISA. Der f 35 showed cross-reactivity with Der f 2 and
      Pso o 2 in reaction with HDM-allergic patients' IgE by ELISA inhibition assay.
      CONCLUSION: Der f 35 is a candidate major allergen from D. farinae, which is more
      similar to group 2 allergens from sheep scab mite and storage mites. Der f 35
      could be responsible for the cross-reactivity among group 2 mite allergens.

PMID- 28439906
TI  - Regenerative endodontic treatment of perforated internal root resorption: a case
      report.
AB  - AIM: To present the regenerative endodontic treatment procedure of a perforated
      internal root resorption case and its clinical and radiographic findings after 2
      years. SUMMARY: A 14-year-old female patient was referred complaining of moderate
      pain associated with her maxillary left lateral incisor. After radiographic
      examination, a perforated internal resorption lesion in the middle third of tooth
      22 was detected. Under local anaesthesia and rubber dam isolation, an access
      cavity was prepared and the root canal was shaped using K-files under copious
      irrigation with 1% NaOCl, 17% EDTA and distilled water. At the end of the first
      and second appointments, calcium hydroxide (CH) paste was placed in the root
      canal using a lentulo. After 3 months, the CH paste was removed using 1% NaOCl
      and 17% EDTA solutions and bleeding in the root canal was achieved by placing a
      size 20 K-file into the periapical tissues. Mineral trioxide aggregate was then
      placed over the blood clot. The access cavity was restored using glass-ionomer
      cement and resin composite. After 2 years, the tooth was asymptomatic and
      radiographic examination revealed hard tissue formation in the perforated
      resorption area and remodelling of the root surface. KEY LEARNING POINTS:
      Regenerative endodontic treatment procedures are an alternative approach to treat
      perforated internal root resorption lesions. Calcium hydroxide was effective as
      an intracanal medicament in regenerative endodontic treatment procedures.

PMID- 28439907
TI  - IgG4-related disease with bone marrow involvement mimicking multiple myeloma.

PMID- 28439908
TI  - Possible role of serum testosterone, gonadotropins and prolactin in patients with
      premature ejaculation.
AB  - Premature ejaculation (PE) is the most common male sexual dysfunction. This study
      aimed to investigate the role of serum testosterone, gonadotropins and prolactin
      in patients with PE. In a prospective a case-controlled study, it was conducted
      on 90 male patients with PE and 90 male healthy participants as controls.
      Patients were evaluated by Premature Ejaculation Diagnostic Tool (PEDT) and
      intravaginal ejaculatory latency time (IELT). Patients with mean IELT values <=60
      s and PEDT total scores >=11 were considered to have PE. Serum levels of total
      testosterone (TT), free testosterone (FT), follicle-stimulating hormone (FSH),
      luteinising hormone (LH) and prolactin (PL) were investigated in patients with PE
      and controls. There was no statistically significant difference between patients
      with PE and controls regarding the serum levels of TT, FT, FSH, LH and PL (p
      value ?.05). There was no significant correlation between the sex hormones levels
      (TT, FT, FSH, LH and PL) and (age, body mass index (BMI), IELTS and total PEDT
      scores of the patients; p value ?.05). This study concluded that there was no
      disturbance in serum levels of testosterone, gonadotropins and prolactin in
      patients with PE and controls. These hormones could not relate to pathogenesis of
      PE.

PMID- 28439909
TI  - Effect of thermally deposited siloxane-methacrylate coating on bonding to glass
      fibre posts.
AB  - AIM: To evaluate the alterations promoted by a thermally deposited siloxane
      methacrylate coating on the surface of glass fibre posts and their effect on the
      bond strength of resin-core materials to the posts. METHODOLOGY: Fibre post
      surfaces were treated with experimental thermally deposited siloxane-methacrylate
      coatings or clinically available treatments (i.e. hydrogen peroxide and methylene
      chloride); nontreated posts were used as controls. The contact angles formed
      between the post surface and the water/adhesive were measured with a tensiometer.
      Scanning electron microscopy and electron dispersive spectroscopy were used to
      examine the topographies and chemical changes in the post surfaces following
      treatment. Surface roughness was evaluated with laser interferometry. Core resin
      was bonded to the fibre posts, and microtensile bond strength testing was
      subsequently performed. The data were individually submitted to anova and Tukey's
      tests (alpha = 0.05). RESULTS: The water contact angle was reduced significantly
      (P < 0.05) by the thermally deposited siloxane-methacrylate coating. All
      treatments significantly increased the adhesive contact angle (P <= 0.016)
      compared to the control as well as the surface roughness (P <= 0.006) and the
      amount of Si on post surfaces. Greater percentages of Si were observed for the
      thermally deposited coating. The bond strength to the posts was significantly
      improved by the thermally deposited coating (P < 0.05), whereas the other
      treatments did not differ from the control. CONCLUSION: Treating the surface of
      glass fibre posts with a thermally deposited siloxane-methacrylate coating
      improved the bond strength to resin-based materials. The coating could be
      performed by manufacturers of glass fibre posts in order to reduce the number of
      clinical steps required for luting posts into root canals.

PMID- 28439910
TI  - ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell
      transplantation for acute myeloid leukemia: A report from the acute leukemia
      working party of the EBMT.
AB  - ABO incompatibility is commonly observed in stem cell transplantation and its
      impact in this setting has been extensively investigated. HLA-mismatched
      unrelated donors (MMURD) are often used as an alternative stem cell source but
      are associated with increased transplant related complications. Whether ABO
      incompatibility affects outcome in MMURD transplantation for acute myeloid
      leukemia (AML) patients is unknown. We evaluated 1,013 AML patients who underwent
      MMURD transplantation between 2005 and 2014. Engraftment rates were comparable
      between ABO matched and mismatched patients, as were relapse incidence [34%; 95%
      confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO
      mismatched; P = .32], and nonrelapse mortality (28%; 95% CI, 23-33; for ABO
      matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P = .2). Three year survival
      was 40% for ABO matched and 43% for ABO mismatched patients (P = .35), Leukemia
      free survival rates were also comparable between groups (37%; 95% CI, 32-43; for
      ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P = .87). Incidence of
      grade II-IV acute graft versus host disease was marginally lower in patients with
      major ABO mismatching (Hazard ratio of 0.7, 95% CI, 0.5-1; P = .049]. ABO
      incompatibility probably has no significant clinical implications in MMURD
      transplantation.

PMID- 28439911
TI  - The impact of an appointment-based medication synchronization programme on
      chronic medication adherence in an adult community pharmacy population.
AB  - WHAT IS KNOWN AND OBJECTIVES: Non-adherence to medication regimens is the primary
      cause of suboptimal clinical benefit in patients with chronic diseases. The
      primary objective of this study was to assess and compare adherence to chronic
      medications among adults participating in Time My Meds (TMM), an appointment
      based medication synchronization programme, to patients receiving usual care.
      METHODS: This was a quasi-experimental study that evaluated data from 18 partner
      community pharmacies in three lower U.S. Midwestern states between January 2013
      and May 2015. RESULTS: During the 6-month post-period, PDC>=0.80 was achieved by
      73.53%, 80.41% and 75.00% of usual care patients taking oral diabetes, renin
      angiotensin system antagonist (RASA) and statin medications. In comparison, the
      PDC threshold was achieved by 100%, 97.94% and 97.62% of TMM patients taking oral
      diabetes, RASA and statin medications (P<.031 in diabetes group and P<.003 in
      RASA group). The percentage of on-time prescription refills increased from 69.68%
      to 84.75% in patients with diabetes, 79.04% to 89.56% in the hypertension group
      and 78.26% to 89.07% in the hyperlipidaemic group. WHAT IS NEW AND CONCLUSION: An
      appointment-based medication synchronization programme in community pharmacies
      resulted in improved adherence and increased percentage of on-time refills.

PMID- 28439912
TI  - Older migrants in exile: the past holding hands with the present - a qualitative
      study.
AB  - The aim of this study was to explore the everyday life conditions experienced by
      older migrants and their reasons for specific age- and health-related behaviour
      during the conduct of everyday life. The study comprised 16 qualitative
      interviews with migrants aged 56-96 years from Palestine, Lebanon, Iraq and
      Somalia. The three themes that emerged from the conditions, meanings and reasons
      analysis illustrated that the older persons were trapped in various ways -without
      language, in fragmented families and in an unfamiliar structure. We identified
      these themes as The importance of the life history, Lost in language barriers and
      Having a national sense of belonging. The main findings emphasise the
      vulnerability of older migrants in a resettlement country. With an unclear
      national identity and without the local language, older migrants struggle to
      develop a clear vision of their role in a minority community in a foreign
      country. Besides language skills and the need for interpreters, health
      professionals need to consider issues such as life history, traumas and national
      belonging when their usual approaches to managing health-related topics have
      failed.

PMID- 28439913
TI  - Workplace culture in psychiatric nursing described by nurses.
AB  - AIM: This study looks to describe the workplace culture from the viewpoints of
      stress, job satisfaction and practice environment. METHODS: Data were collected
      from nurses (n = 109) using a web-based survey, The Person-Centred Nursing Index,
      from two purposefully selected hospital districts in Finland. Data were
      statistically analysed. RESULTS: Nurses described their workplace culture in
      slightly positive terms. Nurses only occasionally experienced stress (mean =
      2.56, SD = 0.55) and were fairly satisfied with their job (mean = 4.75, SD =
      0.66) and their practice environment (mean = 4.42, SD = 0.81). Demographic
      variables such as the nurses' age, length of time in nursing, time at their
      present hospital, working shifts and their use of patient restriction were more
      frequently associated with their perceived workplace culture. CONCLUSION: Older
      nurses and those with a longer work history in the nursing profession tended to
      be more satisfied with their workplace culture in psychiatric nursing. Young
      and/or newly graduated nurses felt more negatively on their workplace culture;
      this issue should be recognised and addressed with appropriate support and
      mentoring. Nurses who used restrictive measures were more often less satisfied
      with their workplace culture. Continuous efforts are needed to reduce the use of
      coercive measures, which challenge also the managers to support nursing practice
      to be more person-centred.

PMID- 28439914
TI  - How does burnout impact the three components of nursing professional commitment?
AB  - BACKGROUND: While the impact of burnout on organisational commitment has been
      widely observed, its impact on nursing professional commitment has not previously
      been investigated. The literature has clarified that professional commitment has
      three distinct components: affective, continuance and normative. AIMS: This study
      aims to investigate the relationships between burnout and the three components of
      nursing professional commitment. METHODS: This was a cross-sectional study using
      questionnaires to collect data in one large medical centre. Responses from 571
      nurses were used for regression analysis. Among the sampled nurses, 90.9% had <15
      years of nursing experience. MBI-HSS was used for measuring burnout. Three
      components of nursing professional commitment came from Meyer et al. (J Appl
      Psychol, 78, 1993 and 538) a formally validated instrument. RESULTS: Analytical
      results indicated that burnout is negatively related to affective and normative
      professional commitment (B <= -0.09, p < 0.01), but not related to continuance
      professional commitment (B = 0.05, p > 0.05). LINKING EVIDENCE TO ACTION: Nurse
      managers aiming to improve nurses' professional commitment should consider
      reducing nurses' burnout, for example improving nursing optimism and reducing
      administrative tasks, as suggested by the literature.

PMID- 28439915
TI  - Treatment of chronic hepatitis C with direct-acting antivirals in patients with
      beta-thalassaemia major and advanced liver disease.
AB  - Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in
      patients with beta-thalasaemia major (beta-TM) due to poor efficacy and
      tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these
      patients. The aim of this study was to assess the safety and efficacy of DAAs in
      patients with beta-TM and advanced liver disease due to CHC. Patients were
      recruited from eight liver units in Greece. The stage of liver disease was
      assessed using transient elastography and/or liver histology. Five regimens were
      used: sofosbuvir (SOF) + ribavirin (RBV); SOF + simeprevir +/- RBV; SOF +
      daclatasvir +/- RBV; ledipasvir/SOF +/- RBV and ombitasvir/paritaprevir-ritonavir
      + dasabuvir +/- RBV. Sixty-one patients (median age 43 years) were included. The
      majority of patients was previously treated for hepatitis C (75%) and had
      cirrhosis (79%). Viral genotype distribution was: G1a: n = 10 (16%); G1b: n = 22
      (36%); G2: n = 2 (3%); G3: n = 14 (23%); G4: n = 13 (22%). The predominant
      chelation therapy was a combination of deferoxamine and deferiprone (35%).
      Overall sustained virological response rates were 90%. All treatment regimens
      were well tolerated and no major adverse events or drug-drug interactions were
      observed. Approximately half of the patients who received RBV (7/16, 44%) had
      increased needs for blood transfusion. Treatment of CHC with DAAs in patients
      with beta-TM and advanced liver disease was highly effective and safe.

PMID- 28439916
TI  - Real-world results of ibrutinib in relapsed/refractory CLL in France: Early
      results on a large series of 428 patients.

PMID- 28439917
TI  - Impact of right and left ventricular systolic dysfunction on perioperative
      outcome and long-term survival after transcatheter aortic valve replacement.
AB  - BACKGROUND: Aim of the study was to determine the impact of right- and left
      ventricular systolic dysfunction on perioperative outcome and long-term survival
      after TAVR. METHODS: Study population consisted of 702 TAVRs between 2009 and
      2014, 345 by TF, 357 by TA route. RV and LV function were determined by TAPSE and
      LVEF measurement during baseline echocardiography. Patients were divided
      according to TAPSE (>18 mm/14-18 mm/<14 mm) and LVEF (>50%/30-50%/<30%) tertiles.
      Outcome at day-30 and Kaplan-Meier 4-year survival were analyzed. RESULTS:
      Impaired RV and LV-function did not adversely affect mortality, stroke, bleeding,
      and vascular-complications at 30 days. Patients with TAPSE < 14 mm displayed
      elevated rate of renal failure requiring dialysis (11%; P < 0.01). Kaplan-Meier
      survival was adversely affected by RV-systolic dysfunction RVSD (P < 0.01).
      Multivariate analysis revealed that impaired RVSD but not LVSD was an independent
      determinant for late mortality (hazard ratio TAPSE 14-18 mm: 1.53; P = 0.02;
      TAPSE <14 mm: 2.12; P < 0.01). CONCLUSIONS: Peri-operative mortality and risk of
      stroke after TAVR are not adversely affected by preexisting RV or LV dysfunction.
      Long-term survival is impaired in patients with RVSD. RVSD but not LVSD is an
      independent risk factor for late mortality. TAVR should be the preferred therapy
      for patients with RVSD and LVSD, especially when patient is suitable for TF.

PMID- 28439918
TI  - Site-specific familial risk and survival of familial and sporadic head and neck
      cancer.
AB  - The vast majority of head and neck cancers (HNCs) are sporadic squamous cell
      carcinomas, smoking and heavy drinking being the main risk factors. However,
      little is known about the possible role of family history and the importance of
      inherited factors versus shared environment. We used Swedish population-based
      registries to study the family history of HNC. In order to estimate the risk for
      family members to get the same cancer, and the risk for cancer-specific death in
      patients with a family history of HNC compared with patients without a family
      history, multivariate Cox proportional hazards analyses were performed. A 1.43
      fold increased risk for developing HNC in the first-degree relatives (FDRs) of
      HNC patients [hazard ratio (HR), 1.43; 95% CI, 1.28-1.61] was found, when
      compared with relatives of healthy controls. In spouses of patients with HNC, the
      risk for developing any HNC was moderately increased (HR, 1.25; 95% CI, 1.01
      1.53), compared with spouses of healthy controls. In addition, a 1.34-fold
      increased risk for death of HNC was found in HNC patients with a family history
      of HNC (HR, 1.34; 95% CI, (1.03-1.73) compared with HNC patients without a family
      history. We found an increased risk for HNC in relatives and spouses of HNC
      patients, when compared with family members of healthy controls. This suggests
      that in addition to inherited factors, shared environmental factors have a
      significant role in the development of the cancer. Family history of HNC was
      associated with worse survival in a newly diagnosed HNC patient.

PMID- 28439919
TI  - Motor polyradiculopathy during pembrolizumab treatment of metastatic melanoma.
AB  - INTRODUCTION: Pembrolizumab, a monoclonal antibody directed against the immune
      checkpoint programmed cell death-1 receptor (PD-1), has improved survival in
      patients with advanced melanoma. Neuromuscular immune-mediated side effects have
      been rarely reported. METHODS: We describe a 44-year-old man with metastatic
      melanoma who presented with progressive muscle weakness after 23 doses of
      pembrolizumab. RESULTS: The patient developed asymmetric, proximal muscle
      weakness and atrophy in all four limbs. Cerebrospinal fluid examination showed
      albuminocytologic dissociation. MRI revealed contrast enhancement of the
      lumbosacral roots. Electrodiagnostic studies demonstrated widespread fibrillation
      potentials in all four limbs, suggesting a generalized motor polyradiculopathy.
      Despite pembrolizumab discontinuation and treatment with steroids and intravenous
      immunoglobulin, limb weakness worsened. Electrodiagnostic studies were repeated,
      and showed marked and diffuse axonal motor damage. Seven weeks after clinical
      onset the patient was treated with plasma exchanges. He showed no further
      deterioration. DISCUSSION: We report a severe motor polyradiculopathy associated
      with an anti-PD-1 agent that expands the spectrum of neuromuscular complications
      of this class of drugs. Muscle Nerve 56: E162-E167, 2017.

PMID- 28439921
TI  - Impact of obstructive sleep apnoea and intermittent hypoxia on cardiovascular and
      cerebrovascular regulation.
AB  - NEW FINDINGS: What is the topic of this review? This review examines the notion
      that obstructive sleep apnoea (OSA) and intermittent hypoxia (IH) have hormetic
      effects on vascular health. What advances does it highlight? Clinical (OSA
      patient) and experimental animal and human models report that IH is detrimental
      to vascular regulation. However, mild IH and, by extension, mild OSA also have
      physiological and clinical benefits. This review highlights clinical and
      experimental animal and human data linking OSA and IH to vascular disease and
      discusses how hormetic effects of OSA and IH relate to OSA severity, IH intensity
      and duration, and patient/subject age. Obstructive sleep apnoea (OSA) is
      associated with increased risk of cardiovascular and cerebrovascular disease, a
      consequence attributed in part to chronic intermittent hypoxia (IH) resulting
      from repetitive apnoeas during sleep. Although findings from experimental animal,
      and human, models have shown that IH is detrimental to vascular regulation, the
      severity of IH used in many of these animal studies [e.g. inspired fraction of
      oxygen (FI,O2) = 2-3%; oxygen desaturation index = 120 events h-1 ] is
      considerably greater than that observed in the majority of patients with OSA.
      This may also explain disparities between animal and recently developed human
      models of IH, where IH severity is, by necessity, less severe (e.g. FI,O2 = 10
      12%; oxygen desaturation index = 15-30 events h-1 ). In this review, we highlight
      the current knowledge regarding the impact of OSA and IH on cardiovascular and
      cerebrovascular regulation. In addition, we critically discuss the recent notion
      that OSA and IH may have hormetic effects on vascular health depending on
      conditions such as OSA severity, IH intensity and duration, and age. In general,
      data support an independent causal link between OSA and vascular disease,
      particularly for patients with severe OSA. However, the data are equivocal for
      older OSA patients and patients with mild OSA, because advanced age and short
      duration, low-intensity IH have been reported to provide a degree of protection
      against IH and ischaemic events such as myocardial infarction and stroke,
      respectively. Overall, additional studies are needed to investigate the
      beneficial/detrimental effects of mild OSA on the various vascular beds.

PMID- 28439920
TI  - Understanding human thiol dioxygenase enzymes: structure to function, and biology
      to pathology.
AB  - Amino acid metabolism is a significant metabolic activity in humans, especially
      of sulphur-containing amino acids, methionine and cysteine (Cys). Cys is
      cytotoxic and neurotoxic in nature; hence, mammalian cells maintain a constant
      intracellular level of Cys. Metabolism of Cys is mainly regulated by two thiol
      dioxygenases: cysteine dioxygenase (CDO) and 2-aminoethanethiol dioxygenase
      (ADO). CDO and ADO are the only human thiol dioxygenases reported with a role in
      Cys metabolism and localized to mitochondria. This metabolic pathway is important
      in various human disorders, as it is responsible for the synthesis of antioxidant
      glutathione and is also for the synthesis of hypotaurine and taurine. CDO is the
      most extensively studied protein, whose high-resolution crystallographic
      structures have been solved. As compared to CDO, ADO is less studied, even though
      it has a key role in cysteamine metabolism. To further understand ADO's structure
      and function, the three-dimensional structures have been predicted from I-TASSER
      and SWISS-MODEL servers and validated with PROCHECK software. Structural
      superimposition approach using iPBA web server further confirmed near-identical
      structures (including active sites) for the predicted protein models of ADO as
      compared to CDO. In addition, protein-protein interaction and their association
      in patho-physiology are crucial in understanding protein functions. Both ADO and
      CDO interacting partner profiles have been presented using STRING database. In
      this study, we have predicted a 3D model structure for ADO and summarized the
      biological roles and the pathological consequences which are associated with the
      altered expression and functioning of ADO and CDO in case of cancer,
      neurodegenerative disorders and other human diseases.

PMID- 28439922
TI  - Illicit drug use among New Zealand gay and bisexual men: Prevalence and
      association with sexual health behaviours.
AB  - INTRODUCTION AND AIMS: Data are lacking on drug use among gay and bisexual men
      (GBM) in New Zealand. We establish a baseline estimate of drug use and
      investigate associations with sexual health and HIV risk. DESIGN AND METHODS: A
      cross-sectional survey of GBM was conducted in gay community settings and online.
      Participants were asked their frequency of using nine drugs (poppers, cannabis,
      ecstasy, methamphetamine, amphetamine, cocaine, LSD, gamma hydroxybutyrate and
      ketamine) in the previous 6 months. We examined associations between selected
      drugs and number of recent partners, unprotected anal intercourse with a casual
      partner and sexually transmitted infections using adjusted odds ratios (AOR).
      RESULTS: Overall, 3211 participants provided information of whom 55.8% reported
      any drug use, and 37.9% cannabis, 36.7% poppers, 16.5% ecstasy, 10.5%
      amphetamine, 7.4% methamphetamine, 6.6% LSD, 6.1% cocaine, 5.3% gamma
      hydroxybutyrate and 4.4% ketamine use. A quarter of all respondents (25.6%)
      reported using one drug, 22.8% two to four and 7.4% five or more drugs
      (polydrugs). Methamphetamine and polydrug use was independently predictive of
      reporting >20 recent partners (AOR 1.6 and 7.0, respectively), unprotected anal
      intercourse with a casual partner (AOR 1.8 and 3.2, respectively) and a sexually
      transmitted infection (AOR 1.6 and 4.3, respectively). DISCUSSION AND
      CONCLUSIONS: Drug use was common in this sample of GBM. Polydrug and
      methamphetamine users had especially high sexual health needs, but risks remained
      elevated among GBM consuming other drugs. Drug harm reduction programs and HIV
      prevention should target GBM with problematic drug use. Limitations include an
      inability to attribute causation. [Saxton P, Newcombe D, Ahmed A, Dickson N,
      Hughes A. Illicit drug use among New Zealand gay and bisexual men: Prevalence and
      association with sexual health behaviours. Drug Alcohol Rev 2017;00:000-000].

PMID- 28439923
TI  - Immunosuppressive drugs in whole blood: validation of a commercially available
      liquid chromatography/tandem mass spectrometry kit and comparison with
      immunochemical assays.
AB  - RATIONALE: In the determination of immunosuppressive drugs cyclosporine A (CSA),
      tacrolimus (TARO), sirolimus (SIRO), and everolimus (EVE) in whole blood there is
      an open debate about which is the best assay between immunochemistry and liquid
      chromatography/tandem mass spectrometry (LC/MS/MS). This work is aimed to explore
      this topic, focusing on the use of updated assays and the analysis of a large
      number of samples. METHODS: A certified in vitro diagnostic kit coupled with a
      medical device LC/MS/MS was validated and applied to the analysis of 1192 blood
      samples of patients treated with immunosuppressive drugs. The results were
      compared with those obtained by immunoassays. RESULTS: The LC/MS/MS approach was
      found to provide linear, stable, precise, and accurate results, with lower limits
      of quantification of 12.5, 1.1, 1.2, and 1.2 MUg/L for CSA, TACRO, SIRO, and EVE,
      respectively. With this method 80 samples were analysed and reported within a
      single work shift. A correlation was observed between the LC/MS/MS and
      immunoassay data, with Spearman correlation coefficients of 0.980 (n = 260) for
      CSA, 0.836 for TACRO (n = 562), 0.898 for SIRO (n = 113), and 0.904 for EVE (n =
      257). Passing-Bablock regression showed the presence of constant and proportional
      biases for most of the drugs. A Blond-Altman graph showed differences between the
      assays, with immunoassays generally overestimating the drugs. CONCLUSIONS: The
      LC/MS/MS certified kit was validated for the detection of immunosuppressant drugs
      in whole blood and it provided a high-throughput method that is consistent with
      the requirements of clinical laboratories. The comparison of patient data between
      LC/MS/MS and up-dated immunoassays shows that a significant discrepancy still
      exists, especially for CSA and SIRO, confirming the greater specificity
      associated with use of the LC/MS/MS assay Copyright (c) 2017 John Wiley & Sons,
      Ltd.

PMID- 28439924
TI  - Prevalence and predictors of thyroid functional abnormalities in newly diagnosed
      AL amyloidosis.
AB  - BACKGROUND: Data on the effect of systemic immunoglobulin light chain amyloidosis
      (AL amyloidosis) on thyroid function are limited. OBJECTIVE: To assess the
      prevalence of hypothyroidism in AL amyloidosis patients and determine its
      predictors. METHODS: 1142 newly diagnosed AL amyloidosis patients were grouped
      based on the thyroid-stimulating hormone (TSH) measurement at diagnosis:
      hypothyroid group (TSH above upper normal reference; >5 mIU L-1 ; n = 217, 19% of
      study participants) and euthyroid group (n = 925, 81%). Predictors for
      hypothyroidism were assessed in a binary multivariate model. Survival between
      groups was compared using the log-rank test and a multivariate analysis. RESULTS:
      Patients with hypothyroidism were older, more likely to present with renal and
      hepatic involvement and had a higher light chain burden compared to patients in
      the euthyroid group. Higher proteinuria in patients with renal involvement and
      lower albumin in patients with hepatic involvement were associated with
      hypothyroidism. In a binary logistic regression model, age >=65 years, female
      sex, renal involvement, hepatic involvement, kappa light chain restriction and
      amiodarone use were independently associated with hypothyroidism. Ninety-three
      per cent of patients in the hypothyroid group with free thyroxine measurement had
      normal values, consistent with subclinical hypothyroidism. Patients in the
      hypothyroid group had a shorter survival compared to patients in the euthyroid
      group (4-year survival 36% vs 43%; P = 0.008), a difference that was maintained
      in a multivariate analysis. CONCLUSION: A significant proportion of patients with
      AL amyloidosis present with hypothyroidism, predominantly subclinical, which
      carries a survival disadvantage. Routine assessment of TSH in these patients is
      warranted.

PMID- 28439925
TI  - Work-related psychosocial stress and the risk of type 2 diabetes in later life.
AB  - OBJECTIVES: Although work-related psychosocial stress and type 2 diabetes
      mellitus (T2DM) have been investigated, the association between lifelong work
      stress and T2DM in later life remains unclear. This study examined whether high
      work stress increased the risk of T2DM risk in later life, accounting also for
      other sources of stress outside work, such as burden from household chores.
      METHODS: From the population-based prospective study SNAC-K, 2719 diabetes-free
      participants aged >=60 years were identified and followed up for 6 years. T2DM
      was ascertained by glycated haemoglobin level, self-report, hypoglycaemic
      medication use and clinical records. Levels of job control and demands over the
      whole working life were assessed by a validated matrix. Household chores load was
      assessed by hours spent on such chores. Multivariate logistic regression models
      were used to estimate the association between job strain and T2DM. RESULTS:
      During the 6-year follow-up, 154 incident cases of T2DM were identified. High job
      strain was associated with T2DM occurrence amongst the 60-year-old cohort (OR =
      3.14, 95% CI: 1.27-7.77), and only amongst women (OR = 6.18, 95% CI: 1.22-31.26),
      but not in men. When taking into account household chores load, a more pronounced
      risk of T2DM was associated with high job strain in combination with heavy
      household chores load in women aged 60 years at baseline (OR = 9.45, 95% CI: 1.17
      76.53). CONCLUSION: Work-related psychosocial stress may increase the risk of
      T2DM only amongst women in their early 60s. The risk can be amplified by high
      household chores load.

PMID- 28439926
TI  - Multi-Nonvolatile State Resistive Switching Arising from Ferroelectricity and
      Oxygen Vacancy Migration.
AB  - Resistive switching phenomena form the basis of competing memory technologies.
      Among them, resistive switching, originating from oxygen vacancy migration (OVM),
      and ferroelectric switching offer two promising approaches. OVM in oxide
      films/heterostructures can exhibit high/low resistive state via conducting
      filament forming/deforming, while the resistive switching of ferroelectric tunnel
      junctions (FTJs) arises from barrier height or width variation while
      ferroelectric polarization reverses between asymmetric electrodes. Here the
      authors demonstrate a coexistence of OVM and ferroelectric induced resistive
      switching in a BaTiO3 FTJ by comparing BaTiO3 with SrTiO3 based tunnel junctions.
      This coexistence results in two distinguishable loops with multi-nonvolatile
      resistive states. The primary loop originates from the ferroelectric switching.
      The second loop emerges at a voltage close to the SrTiO3 switching voltage,
      showing OVM being its origin. BaTiO3 based devices with controlled oxygen
      vacancies enable us to combine the benefits of both OVM and ferroelectric
      tunneling to produce multistate nonvolatile memory devices.

PMID- 28439927
TI  - Antithrombotic therapy and platelet transfusions in hematologic malignancy
      patients presenting chemotherapy-induced thrombocytopenia: a French survey.
AB  - BACKGROUND: Patients with hematologic malignancies are at high risk for both
      thrombosis and bleeding. During the prolonged periods of thrombocytopenia
      experienced by patients who are receiving intensive chemotherapy, clinicians
      often hesitate to prescribe any protection against thrombosis. In case of
      anticoagulant prescription, it is the prescribers' responsibility to weigh risks
      and benefits for each patient. Current guidelines exist but do not take into
      account types of thrombosis, patients' comorbidities, or previous bleeding
      events. STUDY DESIGN AND METHODS: We proposed to gain insight into hematologists'
      beliefs about antithrombotic prescription in hematologic malignancy patients, to
      design future clinical trials. Therefore, we conducted a survey in France to
      evaluate the practices among a panel of hematologists. RESULTS: We found that
      more than 92% of the respondents prescribed therapeutic anticoagulation in case
      of pulmonary embolism or deep venous thrombosis. In the case of therapeutic
      anticoagulation, only 64% of the physicians reconsidered treatment under a
      platelet threshold of 50 * 109 /L. None of the respondents decided to renounce
      treatment, nor to discontinue it because of thrombocytopenia, except in distal
      venous thrombosis or superficial vein thrombosis. One-fifth of clinicians
      proposed the insertion of a vena cava filter. CONCLUSION: As observed in the
      United States and Canada, we noticed discrepancies between recommendations and
      current practices in France. This highlights the urgent need to conduct studies
      to evaluate both efficacy and safety of antithrombotics in patients with
      hematologic cancer and thrombocytopenia.

PMID- 28439928
TI  - Effect of ultrasonic activation on the reduction of bacteria and endotoxins in
      root canals: a randomized clinical trial.
AB  - AIM: This randomized clinical trial aimed to compare the effectiveness of
      ultrasonic activation with that of nonactivated irrigation on the removal of
      bacteria and endotoxin from root canals. METHODOLOGY: Fifty patients with
      necrotic pulps and asymptomatic apical periodontitis were randomly allocated into
      two groups according to the final irrigation protocol after root canal
      preparation: Group UI - ultrasonic irrigation (n = 25) and Group NI - needle
      irrigation (n = 25). The root canals were medicated with calcium hydroxide for 14
      days. Microbiological sampling was performed before (S1) and after the root canal
      preparation (S2), after the irrigation protocols (S3) and after the removal of
      the intracanal medication (S4). Total bacteria counts were determined by qPCR and
      the endotoxin levels by the limulus amebocyte lysate assay. Intragroup analyses
      were performed using the Wilcoxon test for related samples, whereas intergroup
      analyses were performed using the Mann-Whitney U-test (P < 0.05). RESULTS: All S1
      samples were positive for bacteria, with median numbers of 1.49 * 106 and 8.55 *
      105 bacterial cells for the UI and NI groups, respectively. This number
      significantly decreased in S2 samples (UI: 1.41 * 104 ; NI: 3.53 * 104 ; both
      with P < 0.001). After final irrigation protocols, there was a significant
      decrease in bacterial load from S2 to S3 samples in both groups (UI: 4.29 * 103 ;
      NI: 1.08 * 104 ; P < 0.01). Intergroup analysis revealed a significant difference
      between irrigation methods regarding bacterial counts in S3 samples (P < 0.05).
      In contrast, no significant differences were observed between groups for
      endotoxin levels (P > 0.05). CONCLUSIONS: Ultrasonic activation was more
      effective than nonactivated irrigation for reducing the number of bacteria but
      not the endotoxin levels in root canals of teeth with apical periodontitis.

PMID- 28439929
TI  - The roles of autophagy and hypoxia in human inflammatory periapical lesions.
AB  - AIM: To determine the expressions of hypoxia-related [hypoxia-inducible
      transcription factors (HIF)-1alpha, BCL2/adenovirus E1B 19 kDa protein
      interacting protein 3 (BNIP3) and phospho-adenosine monophosphate activated
      protein kinase (pAMPK)] and autophagy-related [microtubule-associated protein 1
      light chain 3 (LC3), beclin-1 (BECN-1), autophagy-related gene (Atg)5-12, and
      p62] proteins in human inflammatory periapical lesions. METHODOLOGY: Fifteen
      samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined
      with 17 healthy dental pulp tissues, were examined. Enzyme-linked immunosorbent
      assay (ELISA) was used to detect interleukin (IL)-1beta cytokine;
      immunohistochemical (IHC) and Western blot (WB) analyses were employed to examine
      autophagy-related and hypoxia-related proteins. Transmission electron microscopy
      (TEM) was used to explore the ultrastructural morphology of autophagy in
      periapical lesions. Nonparametric Kruskal-Wallis tests and Mann-Whitney U-tests
      were used for statistical analyses. RESULTS: ELISA revealed a significantly
      higher (P < 0.001) IL-1beta expression in periapical lesions than in normal pulp
      tissue. Immunoscores of IHC expressions of pAMPK, HIF-1alpha, BNIP3, BECN-1 and
      Atg5-12 proteins in periapical lesions were significantly higher (P < 0.001)
      (except BECN-1) than those in normal pulp tissue. The results of IHC studies were
      largely compatible with those of WB analyses, where significantly higher (P <
      0.05) expressions of hypoxia-related and autophagy-related proteins (except BECN
      1, p62 and LC3II in WB analyses) in periapical lesions were noted as compared to
      normal pulp tissue. Upon TEM, ultrastructural double-membrane autophagosomes and
      autolysosomes were observed in PGs and RCs. CONCLUSIONS: Autophagy associated
      with hypoxia may play a potential causative role in the development and
      maintenance of inflamed periapical lesions.

PMID- 28439930
TI  - Detection and identification of platelet antibodies using a sensitive multiplex
      assay system-platelet antibody bead array.
AB  - BACKGROUND: Tests for platelet-specific antibodies are important in the diagnosis
      of immune platelet disorders. Monoclonal antibody glycoprotein capture assays
      have been the gold standards in platelet antibody detection for almost 30 years.
      However, such assays are complex and cumbersome to perform, which limits their
      routine use. We report the performance of a newly developed, easy to perform
      platelet antibody bead array (PABA) for the detection of platelet-specific
      antibodies. STUDY DESIGN AND METHODS: PABA is the equivalent of the monoclonal
      antigen capture enzyme-linked immunosorbent assay (ELISA) (MACE) on a bead and
      instead with fluorescent detection of immunoglobulin (Ig)G platelet antibodies by
      Luminex. Antibodies against platelet glycoproteins (GP) GPIIb/IIIa, GPIb/IX,
      GPIa/IIa, GPIV, and class I human leukocyte antigen (HLA) could be detected in a
      patient's serum simultaneously in a single well of a microplate. Results from 80
      patient samples and 20 normal donor samples were compared using PABA, MACE, and a
      commercial ELISA kit. RESULTS: PABA detected all antibodies, with specificity for
      human platelet antigens (HPAs) HPA-1a, HPA-1b, HPA-2a, HPA-2b, HPA-3a, HPA-3b,
      HPA-4a, HPA-4b, HPA-5a, HPA-5b, HPA-15b, and HLA. Overall, compared with MACE,
      the sensitivity and specificity of PABA were 99% and 97%, respectively, and both
      were significantly better than those of the commercial ELISA. PABA had greater
      analytic sensitivity than MACE for HPA-1a, HPA-3a, and HPA-5b antibodies. In
      addition, PABA detected HPA-5b and HPA-3b antibodies that were missed by MACE.
      The overall false-positive rate of PABA compared with MACE was 2.7%. CONCLUSIONS:
      The PABA is a rapid, highly sensitive and specific, multiplex bead-based assay
      for detecting human platelet antibodies. Such a simple yet high-throughput
      platform will facilitate practical, routine testing for the identification of
      platelet-specific antibodies.

PMID- 28439931
TI  - Angioleiomyoma mimicking pes anserinus bursitis: A case report.

PMID- 28439932
TI  - Photophysical Characterization of the Naturally Occurring Dioxobacteriochlorin
      Tolyporphin A and Synthetic Oxobacteriochlorin Analogues.
AB  - Tolyporphins are tetrapyrrole macrocycles produced by a cyanobacterium-containing
      culture known as HT-58-2. Tolyporphins A-J are free base dioxobacteriochlorins,
      whereas tolyporphin K is an oxochlorin. Here, the photophysical characterization
      is reported of tolyporphin A and two synthetic analogues, an oxobacteriochlorin
      and a dioxobacteriochlorin. The characterization (in toluene, diethyl ether,
      ethyl acetate, dichloromethane, 1-pentanol, 2-butanone, ethanol, methanol, N,N
      dimethylformamide and dimethylsulfoxide) includes static absorption and
      fluorescence spectra, fluorescence quantum yields and time-resolved data. The
      data afford the lifetime of the lowest singlet excited state and the yields of
      the nonradiative decay pathways (intersystem crossing and internal conversion).
      The three macrocycles exhibit only modest variation in spectroscopic and excited
      state photophysical parameters across the solvents. The long-wavelength (Qy )
      absorption band of tolyporphin A appears at ~680 nm and is remarkably narrow
      (full-width-at-half-maximum ~7 nm). The position of the long-wavelength (Qy )
      absorption band of tolyporphin A (~680 nm) more closely resembles that of
      chlorophyll a (662 nm) than bacteriochlorophyll a (772 nm). The absorption
      spectra of tolyporphins B-I, K (which were available in minute quantities) are
      also reported in methanol; the spectra of B-I closely resemble that of
      tolyporphin A. Taken together, tolyporphin A generally exhibits spectral and
      photophysical features resembling those of chlorophyll a.

PMID- 28439934
TI  - An International Prophylaxis Study Group (IPSG) survey of prophylaxis in
      inhibitor positive children/adults with severe haemophilia.

PMID- 28439933
TI  - Effect of anti-IgE in occupational asthma caused by exposure to low molecular
      weight agents.
AB  - BACKGROUND: The role of immunoglobulin (Ig)-E in occupational asthma (OA) due to
      low molecular weight (LMW) agents is not well established compared to classical
      atopic asthma. In this study, we evaluate whether anti-IgE monoclonal antibody
      (mAb) has an effect in a mouse model of OA, using persulfate salts. METHODS: On
      days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate
      (AP) or dimethyl sulfoxide (DMSO). On days 15, 18, and 21, animals were injected
      intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or
      saline. Airway hyper-responsiveness (AHR) using a methacholine test, airway
      inflammation in bronchoalveolar lavage (BAL) and lung tissue, and total free IgE
      in serum samples were analyzed 24, 48, and 96 hours after the last challenge.
      RESULTS: Anti-IgE mAb treatment almost completely neutralized free serum IgE. In
      AP-sensitized and challenged mice, anti-IgE mAb treatment abolished AHR 24 hour
      and 48 hour after the last challenge and significantly reduced the total number
      of eosinophils and neutrophils 48 hour and 96 hour after the last AP challenge
      compared with nontreated mice. Levels of interleukin (IL)-13 in BAL were also
      significantly decreased after anti-IgE administration 24 hour and 48 hour after
      the last AP challenge. Histological analysis of the lung sections from anti-IgE
      treated mice revealed normal inflammatory patterns similar to control groups 48
      hour after the last challenge. CONCLUSIONS: Anti-IgE-treated mice showed a
      significant improvement in asthma features related to the AHR and airway
      inflammation. Anti-IgE mAb has positive effects in OA induced by persulfate
      salts.

PMID- 28439935
TI  - Neonatal immune challenge followed by adult immune challenge induces epigenetic
      susceptibility to aggravated visceral hypersensitivity.
AB  - BACKGROUND: Abdominal pain is one of the major symptoms of inflammatory Bowel
      Disease (IBD). The inflammatory mediators released by colon inflammation are
      known to sensitize the afferent neurons, which is one of the contributors to
      abdominal pain. However, not all IBD patients have abdominal pain, and some
      patients report abdominal pain during remission, suggesting contributions of
      other pathological factors to abdominal pain in IBD. Epidemiological studies
      found early-life gastrointestinal infections a risk factor for IBD symptoms and
      adult-life gastrointestinal infections may trigger the onset of IBD. We
      investigated the hypothesis that neonatal colon immune challenge followed by an
      adult colon immune challenge upregulates spinal cord BDNF that aggravates
      visceral sensitivity over and above that induced by adult colon immune challenge
      alone. METHODS: We induced neonatal and adult colon immune challenges by
      intraluminal administration of trinitrobenzene sulfonic acid to the rat colon.
      KEY RESULTS: We found that neonatal immune challenge triggers epigenetic
      programming that upregulates tyrosine hydroxylase in the locus ceruleus when
      these rats are subjected to an adult colon immune challenge. The upregulation of
      locus ceruleus tyrosine hydroxylase, upregulates norepinephrine in the
      cerebrospinal fluid that acts on adrenergic receptors to enhance pCREB binding to
      the cAMP response element, which recruits histone acetylene transferase (HAT) to
      the BDNF gene to enhance its transcription resulting in aggravated visceromotor
      response to colorectal distension. HAT and adrenergic receptor antagonists block
      the aggravation of visceral sensitivity. CONCLUSION & INFERENCES: HAT and
      adrenergic receptor inhibitors may serve as alternates to opioids and NSAIDS in
      suppressing abdominal pain in IBD.

PMID- 28439936
TI  - HIV-positive men who have sex with men are at high risk of development of
      significant liver fibrosis after an episode of acute hepatitis C.
AB  - Acute hepatitis C virus infection remains a major health concern in human
      immunodeficiency virus(HIV)-infected men who have sex with men (MSM). New direct
      acting antiviral agent (DAA) combination therapy has not yet been approved for
      the treatment for acute hepatitis C virus(HCV), thereby potentially causing
      deferral of HCV treatment. Therefore, we aimed to study the course of liver
      disease after an episode of acute HCV. This study is a retrospective single
      centre cohort of HIV-positive MSM with acute HCV infection. Liver fibrosis was
      estimated by Fibroscan(r) and Fibrotest(r) . Liver-related and non-liver-related
      outcomes were documented. Overall 213 episodes of acute HCV infection in 178 men
      were documented. Median follow-up for all included patients was 38.7 months.
      Spontaneous HCV clearance was found in 10.8% of patients, which was significantly
      associated with older age, lower HCV RNA levels, and higher ALT levels upon
      initial acute HCV diagnosis. Treatment with interferon-based therapy was
      initiated in 86.3% of cases, resulting in a sustained virological response(SVR)
      rate of 70.7%. After 3 years' follow-up, significant liver fibrosis of METAVIR F2
      stage or higher was found in 39.4% of patients after first acute HCV diagnosis.
      Higher age, physician-declared alcoholism, and nonresponse to acute HCV therapy
      were independently associated with higher fibrosis stages. Ten patients died
      during the observation period (IR 1.4/100 patient-years) and four during
      interferon treatment. Significant liver fibrosis is a common finding in HIV
      positive MSM following acute HCV infection despite high treatment uptake and cure
      rates, suggesting the need for close liver disease monitoring particularly if HCV
      treatment is deferred.

PMID- 28439937
TI  - Maternal nutrient restriction during pregnancy and lactation leads to impaired
      right ventricular function in young adult baboons.
AB  - KEY POINTS: Maternal nutrient restriction induces intrauterine growth restriction
      (IUGR) and leads to heightened cardiovascular risks later in life. We report
      right ventricular (RV) filling and ejection abnormalities in IUGR young adult
      baboons using cardiac magnetic resonance imaging. Both functional and
      morphological indicators of poor RV function were seen, many of which were
      similar to effects of ageing, but also with a few key differences. We observed
      more pronounced RV changes compared to our previous report of the left ventricle,
      suggesting there is likely to be a component of isolated RV abnormality in
      addition to expected haemodynamic sequelae from left ventricular dysfunction. In
      particular, our findings raise the suspicion of pulmonary hypertension after
      IUGR. This study establishes that IUGR also leads to impairment of the right
      ventricle in addition to the left ventricle classically studied. ABSTRACT:
      Maternal nutrient restriction induces intrauterine growth restriction (IUGR),
      increasing later life chronic disease including cardiovascular dysfunction. Our
      left ventricular (LV) CMRI studies in IUGR baboons (8 M, 8 F, 5.7 years - human
      equivalent approximately 25 years), control offspring (8 M, 8 F, 5.6 years), and
      normal elderly (OLD) baboons (6 M, 6 F, mean 15.9 years) revealed long-term LV
      abnormalities in IUGR offspring. Although it is known that right ventricular (RV)
      function is dependent on LV health, the IUGR right ventricle remains poorly
      studied. We examined the right ventricle with cardiac magnetic resonance imaging
      in the same cohorts. We observed decreased ejection fraction (49 +/- 2 vs. 33 +/-
      3%, P < 0.001), cardiac index (2.73 +/- 0.27 vs. 1.89 +/- 0.20 l min-1 m-2 , P <
      0.05), early filling rate/body surface area (BSA) (109.2 +/- 7.8 vs. 44.6 +/- 7.3
      ml s-1  m-2 , P < 0.001), wall thickening (61 +/- 3 vs. 44 +/- 5%, P < 0.05), and
      longitudinal shortening (26 +/- 3 vs. 15 +/- 2%, P < 0.01) in IUGR animals with
      increased chamber volumes. Many, but not all, of these changes share similarities
      to normal older animals. Our findings suggest IUGR-induced pulmonary hypertension
      should be further investigated and that atrial volume, pulmonic outflow and
      interventricular septal motion may provide valuable insights into IUGR
      cardiovascular physiology. Overall, our findings reaffirm that gestational and
      neonatal challenges can result in long-term programming of poor offspring
      cardiovascular health. To our knowledge, this is the first study reporting IUGR
      induced programmed adult RV dysfunction in an experimental primate model.

PMID- 28439938
TI  - Intramuscular fat infiltration evaluated by magnetic resonance imaging predicts
      the extensibility of the supraspinatus muscle.
AB  - INTRODUCTION: Rotator cuff (RC) tears result in muscle atrophy and fat
      infiltration within the RC muscles. An estimation of muscle quality and
      deformation, or extensibility, is useful in selecting the most appropriate
      surgical procedure. We determined if noninvasive quantitative assessment of
      intramuscular fat using MRI could be used to predict extensibility of the
      supraspinatus muscle. METHODS: Seventeen cadaveric shoulders were imaged to
      assess intramuscular fat infiltration. Extensibility and histological evaluations
      were then performed. RESULTS: Quantitative fat infiltration positively correlated
      with histological findings and presented a positive correlation with muscle
      extensibility (r = 0.69; P = 0.002). Extensibility was not significantly
      different between shoulders graded with a higher fat content versus those with
      low fat when implementing qualitative methods. DISCUSSION: A noninvasive
      prediction of whole-muscle extensibility may directly guide pre-operative
      planning to determine if the torn edge could efficiently cover the original
      footprint while aiding in postoperative evaluation of RC repair. Muscle Nerve 57:
      129-135, 2018.

PMID- 28439939
TI  - Identification of a polygalacturonase (Cup s 2) as the major CCD-bearing allergen
      in Cupressus sempervirens pollen.
AB  - As IgE glyco-epitopes, also referred to as cross-reactive carbohydrate
      determinants (CCDs), can share significant structural homologies between
      different plants, they are prone to extensive cross-reactivity among allergen
      pollen extracts. Here, cypress pollen allergens, especially a polygalacturonase
      (PG), were further characterized using double one-dimensional electrophoresis (D1
      DE). The presence of specific IgE directed against CCDs was investigated by
      bromelain IgE inhibition and concanavalin A binding assays using sera of cypress
      pollen-sensitized patients. Our results showed that IgE reactivity to CCDs in
      Cupressus sempervirens pollen extracts is mainly related to bromelain-type
      epitopes of a newly identified cypress PG. This glycoprotein has been further
      characterized through an immunoproteomic approach and officially indexed as Cup s
      2 by the WHO/IUIS allergen nomenclature. Cup s 2 could thus be associated with
      the increased prevalence of IgE reactivity to cypress pollen extracts because of
      CCD interference.

PMID- 28439940
TI  - Impact of operator experience and training strategy on procedural outcomes with
      leadless pacing: Insights from the Micra Transcatheter Pacing Study.
AB  - BACKGROUND: Leadless pacemaker systems have been designed to avoid the need for a
      pocket and transvenous lead. However, delivery of this therapy requires a new
      catheter-based procedure. This study evaluates the role of operator experience
      and different training strategies on procedural outcomes. METHODS: A total of 726
      patients underwent implant attempt with the Micra transcatheter pacing system
      (TPS; Medtronic, Minneapolis, MN, USA) by 94 operators trained in a teaching
      laboratory using a simulator, cadaver, and large animal models (lab training) or
      locally at the hospital with simulator/demo model and proctorship (hospital
      training). Procedure success, procedure duration, fluoroscopy time, and safety
      outcomes were compared between training methods and experience (implant case
      number). RESULTS: The Micra TPS procedure was successful in 99.2% of attempts and
      did not differ between the 55 operators trained in the lab setting and the 39
      operators trained locally at the hospital (P = 0.189). Implant case number was
      also not a determinant of procedural success (P = 0.456). Each operator performed
      between one and 55 procedures. Procedure time and fluoroscopy duration decreased
      by 2.0% (P = 0.002) and 3.2% (P < 0.001) compared to the previous case. Major
      complication rate and pericardial effusion rate were not associated with case
      number (P = 0.755 and P = 0.620, respectively). There were no differences in the
      safety outcomes by training method. CONCLUSIONS: Among a large group of
      operators, implantation success was high regardless of experience. While
      procedure duration and fluoroscopy times decreased with implant number,
      complications were low and not associated with case number. Procedure and safety
      outcomes were similar between distinct training methodologies.

PMID- 28439941
TI  - Serological biomarkers detect active joint destruction and inflammation in
      patients with haemophilic arthropathy.
AB  - INTRODUCTION: Progressive arthropathy caused by recurrent joint bleeds is a
      severe complication in haemophilia. AIM: We investigated whether biomarkers of
      cartilage and bone degradation, and inflammation were altered in haemophilia
      patients and whether these biomarkers could identify haemophilia patients with
      arthropathy. METHODS: Serum from 35 haemophilia patients with varying degrees of
      arthropathy and 43 age- and gender-matched control subjects were analysed.
      Biomarkers of cartilage degradation (C2M, COMP, CTX-II, ADAMTS5), cartilage
      formation (PRO-C2), bone formation (PINP), bone resorption (CTX-I) and
      inflammation (hsCRP, CRPM) were measured by ELISA. Arthropathy was assessed by
      radiological evaluation (Pettersson score) and physical examination (Gilbert
      score). RESULTS: In patients with haemophilia, cartilage degradation, measured by
      C2M, CTX-II and COMP, was increased by 25% (P < 0.05) compared with control
      subjects. Levels of the cartilage degradation enzyme, ADAMTS5, were 10% lower in
      haemophilia patients (P < 0.05). Bone formation (PINP) was reduced by 25% (P <
      0.05) in haemophilia patients, whereas bone resorption (CTX-I) was increased by
      30% (P < 0.001). Acute inflammation (hsCRP) was increased by 50% (P < 0.01),
      whereas chronic inflammation (CRPM) was decreased by 25% (P < 0.0001). The
      hsCRP/CRPM ratio was 60% higher (P < 0.001) in haemophilia patients relative to
      control subjects. A biomarker panel combining C2M, CRPM, and ADAMTS5 could
      distinguish haemophilia patients from control subjects with 85.3% accuracy (P <
      0.0001). We found no strong correlation between biomarkers and radiological and
      physical examination of the joint. CONCLUSION: Biomarkers detect increased
      cartilage and bone degradation, and altered inflammatory activity in haemophilia
      patients with arthropathy. These biomarkers could potentially be used to identify
      patients with progressing joint disease.

PMID- 28439942
TI  - Assessment of motion of colonic contents in the human colon using MRI tagging.
AB  - BACKGROUND: We have previously reported a non-invasive, semi-automated technique
      to assess motility of the wall of the ascending colon (AC) using Magnetic
      Resonance Imaging. This study investigated the feasibility of using a tagged MRI
      technique to visualize and assess the degree of flow within the human ascending
      colon in healthy subjects and those suffering from constipation. METHODS: An open
      labeled study of 11 subjects with constipation and 11 subjects without bowel
      disorders was performed. MRI scans were acquired fasted, then 60 and 120 minutes
      after ingestion of a 500 mL macrogol preparation. The amount of free fluid in the
      small and large bowel was assessed using a heavily T2-weighted MRI sequence. The
      internal movement of the contents of the AC was visualized using a cine tagged
      MRI sequence and assessed by a novel analysis technique. Comparisons were made
      between fasting and postprandial scans within individuals, and between the
      constipation and control groups. KEY RESULTS: Macrogol significantly increased
      the mobile, MR visible water content of the ascending colon at 60 minutes
      postingestion compared to fasted data (controls P=.001, constipated group
      P=.0039). The contents of the AC showed increased motion in healthy subjects but
      not in the constipated group with significant differences between groups at 60
      minutes (P<.002) and 120 minutes (P<.003). CONCLUSIONS AND INFERENCES: This study
      successfully demonstrated the use of a novel MRI tagging technique to visualize
      and assess the motion of ascending colon contents following a 500 mL macrogol
      challenge. Significant differences were demonstrated between healthy and
      constipated subjects.

PMID- 28439943
TI  - Botryoid nuclei resulting from cocaine abuse.

PMID- 28439945
TI  - Enhancement of Cardiomyogenesis in Murine Stem Cells by Low-Intensity Ultrasound.
AB  - OBJECTIVES: Low-intensity ultrasound (LIUS) has been shown to enhance bone and
      cartilage regeneration from stem cells. The ease of its incorporation makes it an
      attractive mechanical stimulus for not only osteogenesis and chondrogenesis, but
      also cardiomyogenesis. However, to date, no study has investigated its effects on
      cardiomyogenesis from embryonic stem cells. METHODS: In this study, murine
      embryonic stem cells were differentiated via embryoid body formation and plating,
      and after 3 days they were subjected to daily 10 minutes of LIUS treatment with
      various conditions: (1) low-pulsed (21 mW/cm2 , 20% duty cycle), (2) low
      continuous, (3) high-pulsed (147 mW/cm2 , 20% duty cycle), and (4) high
      continuous LIUS. RESULTS: Low-pulsed and high-continuous LIUS had improved
      beating rates of contractile areas as well as increased late cardiac gene
      expressions, such as alpha- and beta-myosin heavy chain and cardiac troponin T,
      showing its benefits on cardiomyocyte differentiation. Meanwhile, an early
      endodermal marker, alpha-fetoprotein, was significantly attenuated after LIUS
      treatments. CONCLUSIONS: With these observations, it is demonstrated that LIUS
      simulation could enhance cardiomyogenesis from embryonic stem cells and increase
      its selectivity toward cardiomyocytes by reducing spontaneous differentiation.

PMID- 28439944
TI  - Using perimetric data to estimate ganglion cell loss for detecting progression of
      glaucoma: a comparison of models.
AB  - PURPOSE: Models relating perimetric sensitivities to ganglion cell numbers have
      been proposed for combining structural and functional measures from patients with
      glaucoma. Here we compared seven models for ability to differentiate progressing
      and stable patients, testing the hypothesis that the model incorporating local
      spatial scale would have the best performance. METHODS: The models were compared
      for the United Kingdom Glaucoma Treatment Study (UKGTS) data for the right eyes
      of 489 patients recently diagnosed with glaucoma. The SITA 24-2 program was
      utilised for perimetry and Stratus OCT fast scanning protocol for thickness of
      circumpapillary retinal nerve fibre layer (RNFL). The first analysis defined
      progression in terms of decline in RNFL thickness. The highest and lowest
      quintiles (22 subjects per group) were identified for change in thickness of
      inferior temporal (IT), superior temporal (ST), and global RNFL (MUm year-1 ); a
      two-way anova was used to look for differences between the models in ability to
      discriminate the two quintiles. The second analysis defined a 'progression group'
      as those who were flagged by the UKGTS criteria as having progressive loss in
      perimetric sensitivity, and a 'no progression' group as those with rate of change
      in Mean Deviation (MD) closest to 0 dB year-1 (87 subjects per group). The third
      analysis characterised variability of retinal ganglion cell (RGC) models for the
      two groups in the second analysis, using the standard deviation of residuals from
      linear regression of ganglion cell number over time to compute Coefficient of
      Variation (CoV). RESULTS: The first analysis produced a negative result because
      the three anovas found no effect of model or interaction of model and group
      (F6,294 < 3.1, p > 0.08). There was an effect of group only for the anova with
      the ST sector (F6,294 = 12.2, p < 0.001). The second analysis also produced a
      negative result, because ROC areas were in the range 0.69-0.72 for all models.
      The third analysis found that even when variability in MD was low, the CoV was so
      large that test-retest variation could include 100% loss of ganglion cells.
      CONCLUSIONS: Two very different approaches for testing the hypothesis both gave a
      negative result. For all seven ganglion cell models, rates of ganglion cell loss
      were highly affected by fluctuations in height of the hill of vision. Methods for
      reducing effects of between-visit variability are needed in order to assess
      progression by relating perimetric sensitivities and ganglion cell numbers.

PMID- 28439946
TI  - Efficacy and safety of twice- vs once-daily dosing of lisinopril for
      hypertension.
AB  - This retrospective cohort study compared administration of lisinopril twice daily
      and once daily for hypertension. Data were collected from an ambulatory
      electronic health record between 2011 and 2014. Patients previously receiving
      lisinopril 20 mg were placed into the once-daily cohort if changed to 40 mg once
      daily or into the twice-daily cohort if changed to 20 mg twice daily. Efficacy
      outcome measures were change in systolic blood pressure and diastolic blood
      pressure and achievement of blood pressure control (<140/90 mm Hg). Of 90
      patients included (45 per cohort), the mean age was 61.8 years and 17.8% were
      black. Once- and twice-daily administrations were associated with blood pressure
      reductions of 6.2/1.5 mm Hg and 16.5/5.9 mm Hg, with a 10.2/4.3 mm Hg greater
      reduction with twice-daily administration (systolic blood pressure, P=.016;
      diastolic blood pressure, P=.068). Twice-daily lisinopril dosing was associated
      with greater systolic blood pressure reductions compared with the same total
      daily dose administered once daily.

PMID- 28439948
TI  - Keratoacanthoma, palmoplantar keratoderma developing in an advanced melanoma
      patient treated with vemurafenib regressed by blockade of mitogen-activated
      protein kinase kinase signaling.

PMID- 28439947
TI  - SIRT1/HSF1/HSP pathway is essential for exenatide-alleviated, lipid-induced
      hepatic endoplasmic reticulum stress.
AB  - : Recent studies have indicated that lipid-induced endoplasmic reticulum (ER)
      stress is a major contributor to the progression of hepatic steatosis. Exenatide
      (exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve
      hepatic steatosis, with accumulating evidence. In this study, we investigated
      whether exenatide could alleviate lipid-induced hepatic ER stress through mammal
      sirtuin 1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice
      challenged with a high-fat diet (HFD) were treated with exenatide or normal
      saline by intraperitoneal injection for 4 weeks. We observed that HFD feeding
      induced hepatic ER stress as indicated by increased expression of glucose
      regulated protein 78, phosphorylated protein kinase-like ER kinase, and
      phosphorylated eukaryotic initiation factor 2alpha, while these increases were
      significantly inhibited by exenatide. Exenatide notably decreased the liver
      weight and hepatic steatosis induced by HFD challenge. Consistently, in human
      HepG2 cells and primary murine hepatocytes, exendin-4 also significantly
      alleviated the ER stress and lipid accumulation induced by palmitate.
      Importantly, further studies showed that exendin-4 enhanced the binding of heat
      shock factor 1 to the promoter of heat shock protein (HSP) genes through SIRT1
      mediated deacetylation, which then increased the expression of molecular
      chaperones HSP70 and HSP40 to alleviate hepatic ER stress. Finally, inhibition of
      SIRT1 by genetic whole-body heterozygous knockout or by lentiviral short hairpin
      RNA knockdown greatly diminished the effect of exenatide on deacetylating heat
      shock factor 1, increasing HSP expression and alleviating ER stress and hepatic
      steatosis in HFD-fed mice. CONCLUSION: The SIRT1/heat shock factor 1/HSP pathway
      is essential for exenatide-alleviated, lipid-induced ER stress and hepatic
      steatosis, which provides evidence for a molecular mechanism to support exenatide
      and incretin mimetics as promising therapeutics for obesity-induced hepatic
      steatosis. (Hepatology 2017;66:809-824).

PMID- 28439949
TI  - Weight gain and supplemental O2 : Risk factors during the hematopoietic cell
      transplant admission in pediatric patients.
AB  - BACKGROUND: Respiratory failure in the pediatric hematopoietic cell transplant
      (HCT) recipient is the leading cause for admission to the intensive care unit and
      carries a high mortality rate. The objective of this study is to investigate the
      association of clinical risk factors with the development of respiratory failure
      in the pediatric allogeneic HCT recipient. PROCEDURES: This is a single-center,
      retrospective review of allogeneic pediatric HCT from 2008 to 2014. Multiple
      variables were examined. The primary outcome was respiratory failure. Percent
      weight gain was investigated at multiple time points. Bivariate and multivariate
      regression was used. RESULTS: Of the 87 allogeneic HCT recipients, 22 (25%)
      developed respiratory failure. Mortality for entire cohort was 13.8%. All who
      died were intubated prior to death. The group with respiratory failure had
      significantly higher percent weight gain increase at multiple time points: peak
      weight prior to discharge or intubation (P = 0.008), weight at discharge or
      intubation (P = .001), and weight at day 43 (median day for intubation) (P =
      0.02). Odds ratio (OR) for respiratory failure increased with increasing
      percentage peak weight gain: 10% increase (3.1 [1.1, 9.0]), 15% increase (4.1
      [1.5, 11.2]), and 20% (8.3 [2.4. 28.9]). Fifty percent of all patients required
      supplemental O2 . OR for respiratory failure in patients requiring more than 1 l
      supplemental O2 is 25.3 (6.5, 98.7). CONCLUSION: Percent weight gain and need for
      supplemental oxygen is highly associated with the development of respiratory
      failure in pediatric HCT recipients, representing predictors of acute respiratory
      failure in pediatric HCT. These data could be incorporated into an algorithm that
      should be developed, implemented, and validated in a prospective, multicenter
      fashion.

PMID- 28439950
TI  - Protein disulfide isomerase inhibition synergistically enhances the efficacy of
      sorafenib for hepatocellular carcinoma.
AB  - : Sorafenib is the only approved targeted drug for hepatocellular carcinoma
      (HCC), but its effect on patients' survival gain is limited and varies over a
      wide range depending on pathogenetic conditions. Thus, enhancing the efficacy of
      sorafenib and finding a reliable predictive biomarker are crucial to achieve
      efficient control of HCCs. In this study, we utilized a systems approach by
      combining transcriptome analysis of the mRNA changes in HCC cell lines in
      response to sorafenib with network analysis to investigate the action and
      resistance mechanism of sorafenib. Gene list functional enrichment analysis and
      gene set enrichment analysis revealed that proteotoxic stress and apoptosis
      modules are activated in the presence of sorafenib. Further analysis of the
      endoplasmic reticulum stress network model, combined with in vitro experiments,
      showed that introducing an additional stress by treating the orally active
      protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically
      increase the efficacy of sorafenib in vitro and in vivo, which was confirmed
      using a mouse xenograft model. We also found that HCC patients with high PDI
      expression show resistance to sorafenib and poor clinical outcomes, compared to
      the low-PDI-expression group. CONCLUSION: These results suggest that PDI is a
      promising therapeutic target for enhancing the efficacy of sorafenib and can also
      be a biomarker for predicting sorafenib responsiveness. (Hepatology 2017;66:855
      868).

PMID- 28439951
TI  - Incidence and risk factors of hypotension after intravenous fosphenytoin
      administration.
AB  - WHAT IS KNOWN AND OBJECTIVE: Fosphenytoin (FOS) administered intravenously offers
      several benefits over intravenously administered phenytoin, including a faster
      infusion rate, decreased pain and irritation at the infusion site, and fewer
      cardiovascular complications. However, some studies suggest that the intravenous
      administration of FOS in some patients may also induce adverse cardiovascular
      events. Here, we investigated the clinical characteristics of patients who
      experienced hypotension following an intravenous infusion of a FOS loading dose.
      METHODS: We reviewed the medical records of consecutive patients who received an
      intravenous (IV) dose of FOS between July 2013 and June 2015. Various clinical
      and demographic parameters were analysed, including comorbidities, drug history,
      seizure aetiology and type, incidence of hypotension/cardiac arrhythmia and the
      dosing data (ie the total dose, concentration and FOS IV infusion rate).
      Hypotension was defined as a >=20 mm Hg decrease in systolic blood pressure or a
      >=10 mm Hg decrease in diastolic blood pressure during or after FOS IV infusion.
      These parameters were compared between patients with and without hypotension.
      RESULTS AND DISCUSSION: Of the 28 included patients, 11 (39%) had hypotension
      associated with an IV infusion of FOS, two of whom also had an atrioventricular
      block. Most patients (22/28, 79%) who received an IV infusion of FOS had status
      epilepticus (SE). The presence of SE was significantly associated with the
      development of hypotension (P=.026); hypotension occurred in half of the patients
      with SE, but did not occur in six patients without SE. Hypotension was also
      associated with old age (>=60 years, P=.034) and the presence of a systemic
      infection (P=.04). WHAT IS NEW AND CONCLUSION: Our study shows that hypotension
      associated with an IV infusion of FOS is not a rare adverse event, especially in
      patients with SE. Moreover, we found that old age and the presence of a systemic
      infection increased the risk of hypotension. These findings suggest that FOS
      should be infused under careful cardiovascular monitoring, especially in patients
      who are at higher risk of developing hypotension.

PMID- 28439952
TI  - Comparison of cytotoxicity, genotoxicity and immunological inflammatory biomarker
      activity of several endodontic sealers against immortalized human pulp cells.
AB  - AIM: To establish an SV40 T-Ag-transfected cell line of human pulp-derived cells
      in order to compare the cytotoxicity, genotoxicity and to investigate the
      activities of immunological biomarkers of several endodontic sealers.
      METHODOLOGY: Primary human pulp cells and transfected cells were cultured. Cell
      morphology and proliferation were analysed, and the expression of cell-specific
      gene transcripts and proteins was detected by RT-PCR and immunohistochemistry.
      Transfection of human pulp-derived cells resulted in an immortalized cell line
      retaining phenotypic characteristics from the primarily cells tested. The SV40 T
      Ag-transfected cells were cultured and stimulated by sealers (Apexit Plus, Real
      Seal, AH Plus, and EndoREZ) to evaluate the cytotoxicity and genotoxicity by MTT
      and MTN assays, respectively. Immunological inflammatory biomarkers (IL6, IL8 and
      TNF-alpha) were determined by ELISA assay. The differences between median values
      were statistically analysed using Kruskal-Wallis and Dunn's tests at 5%
      significance level. RESULTS: The cytotoxicity assay revealed that
      multimethacrylate (Real Seal) was the most cytotoxic sealer (P < 0.05) and
      exhibited the highest inflammatory potential against the SV40 T-Ag-transfected
      cells (P < 0.05). All root canal sealers tested were able to stimulate the
      immortalized pulp cells to produce IL-6, IL-8 and TNF-alpha, with differences in
      relation to the control group (P < 0.05). Higher levels of IL-6, IL-8 and TNF
      alpha were found in cell supernatant after stimulation with multimethacrylate
      (Real Seal) compared to all other sealers tested (P < 0.05). No differences were
      found comparing epoxy resin-based sealer (AHPlus), single-methacrylate sealer
      (EndoREZ) and calcium hydroxide-based sealer (Apexit Plus), regardless of the
      cytokine investigated (all P > 0.05). CONCLUSIONS: A SV40 T-Ag-transfected cell
      line of human pulp-derived cells was established. The methacrylate resin-based
      sealer (Real Seal) exhibited the greatest cytoxicity and inflammatory potential
      against immortalized pulp cells compared to an epoxy resin-based sealer (AH
      Plus), a methacrylate-based sealer (EndoRez) and a calcium hydroxide-based sealer
      (Apexit).

PMID- 28439954
TI  - Survival and recurrent venous thromboembolism in patients with first proximal or
      isolated distal deep vein thrombosis and no pulmonary embolism.
AB  - : Essentials The long-term risk of recurrence and death after distal deep vein
      thrombosis (DVT) is uncertain. We included subjects with first proximal or
      isolated distal DVT (IDDVT) and no pulmonary embolism. The risk of symptomatic
      and asymptomatic recurrence is lower after IDDVT (vs. proximal). IDDVT may be
      associated with a lower long-term risk of death, especially after unprovoked DVT.
      SUMMARY: Background A few studies have focused on the risk of recurrence after
      first acute isolated distal deep vein thrombosis (IDDVT) compared with proximal
      DVT (PDVT), whereas the incremental risk of death has never been explored beyond
      the first 3 years after acute event. Methods Our single-center cohort study
      included patients with first symptomatic acute PDVT or IDDVT. Patients were
      excluded if they had concomitant pulmonary embolism (PE) or prior venous
      thromboembolism. The primary outcomes were symptomatic objectively diagnosed
      recurrent PDVT or PE and all-cause death. Results In total, 4759 records were
      screened and 831 subjects included: 202 had symptomatic IDDVT and 629 had PDVT.
      The median age was 66 years and 50.5% were women. A total of 125 patients had
      recurrent PDVT or PE during 3175 patient-years of follow-up: 109 events occurred
      after PDVT (17.3%) and 16 after IDDVT (7.9%). Annual recurrence rates were 4.5%
      (95% confidence interval [CI], 3.7-5.4%) and 2.0% (95% CI, 1.1-3.2%),
      respectively, for an adjusted hazard ratio (aHR) for IDDVT patients of 0.32 (95%
      CI, 0.19-0.55). Death occurred in 263 patients (31.6% [95% CI, 28.6-34.9%])
      during 5469 patient-years of follow-up for an overall annual incidence rate of
      4.8% (95% CI, 4.2-5.4%). The mortality rate was 33.5% (n = 211) in PDVT patients
      and 25.7% (n = 52) in IDDVT patients. The long-term hazard of death appeared
      lower for IDDVT patients (aHR, 0.75 [95% CI, 0.55-1.02]), especially after
      unprovoked events (aHR, 0.58 [95% CI, 0.26-1.31]). Conclusions Compared with
      PDVT, IDDVT patients were at a lower risk of recurrent VTE. The risk of death
      appeared lower after IDDVT during a median follow-up of 7.6 years.

PMID- 28439953
TI  - Feasibility trial for primary stroke prevention in children with sickle cell
      anemia in Nigeria (SPIN trial).
AB  - The vast majority of children with sickle cell anemia (SCA) live in Africa, where
      evidence-based guidelines for primary stroke prevention are lacking. In Kano,
      Nigeria, we conducted a feasibility trial to determine the acceptability of
      hydroxyurea therapy for primary stroke prevention in children with abnormal
      transcranial Doppler (TCD) measurements. Children with SCA and abnormal non
      imaging TCD measurements (>=200 cm/s) received moderate fixed-dose hydroxyurea
      therapy (~20 mg/kg/day). A comparison group of children with TCD measurements
      <200 cm/s was followed prospectively. Approximately 88% (330 of 375) of families
      agreed to be screened, while 87% (29 of 33) of those with abnormal TCD
      measurements, enrolled in the trial. No participant elected to withdraw from the
      trial. The average mean corpuscular volume increased from 85.7 fl at baseline to
      95.5 fl at 24 months (not all of the children who crossed over had a 24 month
      visit), demonstrating adherence to hydroxyurea. The comparison group consisted of
      initially 210 children, of which four developed abnormal TCD measurements, and
      were started on hydroxyurea. None of the monthly research visits were missed (n =
      total 603 visits). Two and 10 deaths occurred in the treatment and comparison
      groups, with mortality rates of 2.69 and 1.81 per 100 patient-years, respectively
      (P = .67). Our results provide strong evidence, for high family recruitment,
      retention, and adherence rates, to undertake the first randomized controlled
      trial with hydroxyurea therapy for primary stroke prevention in children with SCA
      living in Africa.

PMID- 28439955
TI  - Recurrent venous thrombosis related to overweight and obesity: results from the
      MEGA follow-up study.
AB  - : Essentials Whether excess body weight influences recurrent venous thrombosis
      (VT) risk is uncertain. We included 3889 VT patients, classified into body mass
      index (BMI) strata to estimate recurrent VT risk. No evidence of an increased
      risk for excess body weight was found. Measuring BMI is not a good tool to
      identify patients at high risk of VT recurrence. SUMMARY: Background Studies on
      the risk of recurrent venous thrombosis in patients with excess body weight have
      yielded conflicting results. Objective To estimate whether excess body weight
      increases the risk of recurrent venous thrombosis. Patients/Methods We included
      3889 patients, followed after a first venous thrombosis for a median of 5.6
      years. Body mass index (BMI) was calculated as weight in kilograms/height in
      meters squared, and classified according to three a priori-defined categories
      (normal weight, overweight, and obesity), as well as by percentiles. Crude
      incidence rates with 95% confidence intervals (CIs) of recurrent venous
      thrombosis were estimated as the number of events over the accumulated follow-up
      time in each BMI category. Cox regression models were used to compare groups,
      adjusted for age and sex. Results The incidence rate of recurrent venous
      thrombosis was 3.3 per 100 patient-years. Adjusted hazard ratios of recurrent
      venous thrombosis in overweight or obese patients in comparison with patients
      with normal weight were 1.05 (95% CI 0.88-1.27) and 0.94 (95% CI 0.74-1.19),
      respectively. Stratification by BMI percentile categories yielded similar
      results. The association between BMI and recurrent venous thrombosis was also
      absent after stratification by sex, (although a small effect for overweight, but
      not for obese women, was found), or into those with a first provoked or
      unprovoked event, or deep vein thrombosis and pulmonary embolism. Conclusions We
      found no evidence of an association between excess body weight and recurrent
      venous thrombosis. Measuring BMI is not a useful tool to identify patients at
      high risk of recurrence.

PMID- 28439956
TI  - Biologic treatments for elderly patients with psoriasis.
AB  - The number of elderly patients with psoriasis is increasing in Japan. However,
      biologic treatment is generally considered to be challenging in elderly patients,
      due to their increased risk of complications compared with younger patients. Our
      retrospective study aimed to evaluate the safety profile and efficacy of
      biologics in senior elderly patients (>=75 years old) with psoriasis. The study
      involved a cohort of 27 patients aged 75-88 years who were being treated with
      biologics over a period of more than 1 year. Initial biologics administrated to
      were adalimumab (five cases) and ustekinumab (22 cases). Eight patients
      discontinued treatment: two developed cancer; one was transferred to hospital;
      and five others experienced either bone fracture, interstitial pneumonia,
      cerebral hemorrhage resulting in death, decrepitude or developed hepatopathy
      following prophylactic tuberculosis treatment. Efficacy, evaluated by the
      percentage of patients achieving 75% reduction of Psoriasis Area and Severity
      Index score, was 76.9% at week 16 (n = 26), 88.0% at week 24 (n = 25) and 90.5%
      at week 52 (n = 21). Biologic treatments thus show clear efficacy in elderly
      patients with psoriasis, however, the increased frequency of adverse events
      requires rigorous patient observation.

PMID- 28439958
TI  - Novel nonsense mutation in SERPINB7 and the treatment of foot odor in a patient
      with Nagashima-type palmoplantar keratosis.

PMID- 28439959
TI  - Chemical and Biological Aspects of Nutritional Immunity-Perspectives for New Anti
      Infectives that Target Iron Uptake Systems.
AB  - Upon bacterial infection, one of the defense mechanisms of the host is the
      withdrawal of essential metal ions, in particular iron, which leads to
      "nutritional immunity". However, bacteria have evolved strategies to overcome
      iron starvation, for example, by stealing iron from the host or other bacteria
      through specific iron chelators with high binding affinity. Fortunately, these
      complex interactions between the host and pathogen that lead to metal homeostasis
      provide several opportunities for interception and, thus, allow the development
      of novel antibacterial compounds. This Review focuses on iron, discusses recent
      highlights, and gives some future perspectives which are relevant in the fight
      against antibiotic resistance.

PMID- 28439960
TI  - Preference for the term pilomatrical carcinoma with melanocytic hyperplasia.

PMID- 28439957
TI  - Prognostic indicators in pediatric clinically isolated syndrome.
AB  - OBJECTIVE: To assess prognostic factors for a second clinical attack and a first
      disability-worsening event in pediatric clinically isolated syndrome (pCIS)
      suggestive of multiple sclerosis (MS) patients. METHODS: A cohort of 770 pCIS
      patients was followed up for at least 10 years. Cox proportional hazard models
      and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to
      analyze data. RESULTS: In pCIS, female sex and a multifocal onset were risk
      factors for a second clinical attack (hazard ratio [HR], 95% confidence interval
      [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying
      drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After
      pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD
      exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)
      worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively),
      whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46
      7.46). An exploratory RECPAM analysis highlighted a significantly higher
      incidence of a first EDSS-worsening event in patients with multifocal or isolated
      spinal cord or optic neuritis involvement at onset in comparison to those with an
      isolated supratentorial or brainstem syndrome. A Cox regression model including
      RECPAM classes confirmed DMD exposure as the most protective factor against EDSS
      worsening events and relapses as the most important risk factor for attaining
      EDSS worsening. INTERPRETATION: This work represents a step forward in
      identifying predictors of unfavorable course in pCIS and POMS and supports a
      protective effect of early DMD treatment in preventing MS development and
      disability accumulation in this population. Ann Neurol 2017;81:729-739.

PMID- 28439961
TI  - Involvement of the cerebellum in Parkinson disease and dementia with Lewy bodies.
AB  - Brains from patients with Parkinson disease or dementia with Lewy bodies show
      aggregation of alpha-synuclein in precerebellar brainstem structures.
      Furthermore, patients exhibit resting tremor, unstable gait, and impaired
      balance, which may be associated with cerebellar dysfunction. Therefore, we
      screened the cerebella of 12 patients with alpha-synucleinopathies for
      neuropathological changes. Cerebellar nuclei and neighboring white matter
      displayed numerous aggregates, whereas lobules were mildly affected. Cerebellar
      aggregation pathology may suggest a prionlike spread originating from affected
      precerebellar structures, and the high homogeneity between patients with dementia
      with Lewy bodies and Parkinson disease shows that both diseases likely belong to
      the same neuropathological spectrum. Ann Neurol 2017;81:898-903.

PMID- 28439962
TI  - Balancing task focus and relationship building: asking sleepy patients about
      traffic risk in treatment initiation consultations.
AB  - BACKGROUND: The use of traffic risk assessment questions is an understudied area
      in nursing research. Obstructive sleep apnoea is associated with an increased
      risk of traffic accidents. Therefore, traffic safety authorities demand adherent
      continuous positive airway pressure use. Nurses act as coaches to achieve
      treatment adherence, but they are also obliged to act as state agents by
      prohibiting obstructive sleep apnoea patients from drowsy driving. OBJECTIVE: To
      examine how nurses and obstructive sleep apnoea patients manage traffic risk
      assessment questions in the relation-building context of treatment initiation
      consultations. METHODS: To study, in detail, the actual practice of risk
      assessment, we used conversation analysis of 19 video-recorded initial treatment
      consultations with nurses and recently diagnosed obstructive sleep apnoea
      patients. ETHICS: The study received ethical approval from the Central Ethical
      Review Board in Linkoping (registration number 214/231-32) and follows the
      ethical guidelines for qualitative research. RESULTS: Patients influence how
      nurses phrase questions about traffic risk by taking a stance to daytime
      sleepiness prior to the risk question. Nurses ask traffic risk questions in a way
      that assumes that driving is unproblematic if patients have not previously
      indicated problems. It may pose a significant problem when nurses, by accepting
      patients' prior stance when asking about traffic risk, orient to relationship
      building rather than task focus. CONCLUSION: To clarify the difference between
      their two potentially conflicting roles, nurses need to refer to existing laws
      and official guidelines when they raise the issue of risk in treatment initiation
      consultations. Nurses should also ask risk assessment questions in a problem
      oriented communicative environment. Traffic risk assessment is sensitive yet
      important, as obstructive sleep apnoea is a highly prevalent problem causing
      excessive sleepiness. It is essential to acknowledge nurses' double roles with
      regard to coaching continuous positive airway pressure treatment and assessing
      traffic risk.

PMID- 28439963
TI  - Diastolic pressure above optimal is the most important predictor of subsequent
      hypertension in normotensive patients younger 50 years.

PMID- 28439964
TI  - Global and targeted metabolomics of synovial fluid discovers special
      osteoarthritis metabolites.
AB  - To identify special metabolites in synovial fluid of osteoarthritis (OA) via a
      metabolomics approach. Synovial fluid of 35 participants (25 OA patients and 10
      controls) was detected by GC-TOF/MS and multivariate data analysis was applied to
      analyze correlation among the observations. Different metabolites were screened
      by VIP value (VIP > 1), student t-test (p < 0.05), and fold change (fold >1.5),
      and verified with the standard metabolites in the synovial fluid of 24 OA
      patients and 11 controls by LC/MS. The classification performance of different
      metabolites was analyzed by receiver operating characteristic (ROC) analysis. The
      results showed that six different metabolites (glutamine, 1,5-anhydroglucitol,
      gluconic lactone, tyramine, threonine, and 8-aminocaprylic acid) were strongly
      associated with OA in global metabolomics. Verified results of the first three
      metabolites were the same as the identified results using targeted metabolomics.
      ROC curve analysis demonstrated that their concentrations in synovial fluid were
      strongly correlated to OA. In addition, the concentrations of gluconic lactone
      were significantly different between OA and RA. Metabolites with altered levels
      may be contributors to OA pathogenesis and can be used as potential diagnosis
      criteria for OA. Gluconic lactone may prove to be a novel criterion for
      differential diagnosis of OA from RA. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 35:1973-1981, 2017.

PMID- 28439965
TI  - Identifying signatures of positive selection in pigmentation genes in two South
      Asian populations.
AB  - OBJECTIVES: Skin pigmentation is a polygenic trait showing wide phenotypic
      variations among global populations. While numerous pigmentation genes have been
      identified to be under positive selection among European and East populations,
      genes contributing to phenotypic variation in skin pigmentation within and among
      South Asian populations are still poorly understood. The present study uses data
      from the Phase 3 of the 1000 genomes project focusing on two South Asian
      populations-GIH (Gujarati Indian from Houston, Texas) and ITU (Indian Telugu from
      UK), so as to decode the genetic architecture involved in adaptation to
      ultraviolet radiation in South Asian populations. METHODS: Statistical tests
      included were (1) tests to identify deviations of the Site Frequency Spectrum
      (SFS) from neutral expectations (Tajima's D, Fay and Wu's H and Fu and Li's D*
      and F*), (2) tests focused on the identification of high-frequency haplotypes
      with extended linkage disequilibrium (iHS and Rsb), and (3) tests based on
      genetic differentiation between populations (LSBL). RESULTS: Twenty-two
      pigmentation genes fall in the top 1% for at least one statistic in the GIH
      population, 5 of which (LYST, OCA2, SLC24A5, SLC45A2, and TYR) have been
      previously associated with normal variation in skin, hair, or eye color. In
      comparison, 17 genes fall in the top 1% for at least one statistic in the ITU
      population. Twelve loci which are identified as outliers in the ITU scan were
      also identified in the GIH population. CONCLUSIONS: These results suggest that
      selection may have affected these loci broadly across the region.

PMID- 28439966
TI  - Automated Fractional Limb Volume Measurements Improve the Precision of Birth
      Weight Predictions in Late Third-Trimester Fetuses.
AB  - OBJECTIVES: Fetal soft tissue can be assessed by using fractional limb volume as
      a proxy for in utero nutritional status. We investigated automated fractional
      limb volume for rapid estimate fetal weight assessment. METHODS: Pregnant women
      were prospectively scanned for 2- and 3-dimensional fetal biometric measurements
      within 4 days of delivery. Performance of birth weight prediction models was
      compared: (1) Hadlock (Am J Obstet Gynecol 1985; 151:333-337; biparietal
      diameter, abdominal circumference, and femur diaphysis length); and (2) Lee
      (Ultrasound Obstet Gynecol 2009; 34:556-565; biparietal diameter, abdominal
      circumference, and automated fractional limb volume). Percent differences were
      calculated: [(estimated birth weight - actual birth weight) / (actual birth
      weight] * 100. Systematic errors (accuracy) were summarized as signed mean
      percent differences. Random errors (precision) were calculated as +/- 1 SD of
      percent differences. RESULTS: Fifty neonates were delivered at 39.4 weeks'
      gestation. The Hadlock model generated the most accurate birth weight (0.31%)
      with a mean random error of +/-7.9%. Despite systematic underestimations, the
      most precise results occurred with fractional arm volume (-9.1% +/- 5.1%) and
      fractional thigh (-5.2% +/- 5.2%) models. The size and distribution of these
      prediction errors were improved after correction for systematic errors.
      CONCLUSIONS: Automated fractional limb volume measurements can improve the
      precision of weight predictions in third-trimester fetuses. Correction factors
      may be necessary to adjust underestimated systematic errors when using automated
      fractional limb volume with prediction models that are based on manual tracing of
      fetal limb soft tissue borders.

PMID- 28439967
TI  - Involvement of the heparanase procoagulant domain in bleeding and wound healing.
AB  - : Essentials Heparanase forms a complex with tissue factor and enhances the
      generation of factor Xa. The present study was aimed to identify the procoagulant
      domain of heparanase. Procoagulant peptides significantly shortened bleeding time
      and enhanced wound healing. Tissue factor pathway inhibitor (TFPI)-2 derived
      peptides inhibited the procoagulant peptides. SUMMARY: Background Heparanase,
      which is known to be involved in angiogenesis and metastasis, was shown to form a
      complex with tissue factor (TF) and to enhance the generation of activated factor
      X (FXa). Our study demonstrated that peptides derived from TF pathway inhibitor
      (TFPI)-2 impeded the procoagulant effect of heparanase, and attenuated
      inflammation, tumor growth, and vascularization. Aims To identify the
      procoagulant domain in the heparanase molecule, and to evaluate its effects in a
      model of wound healing that involves inflammation and angiogenesis. Methods
      Twenty-four potential peptides derived from heparanase were generated, and their
      effect was studied in an assay of FXa generation. Peptides 14 and 16, which
      showed the best procoagulant effect, were studied in a bleeding mouse model and
      in a wound-healing mouse model. Results Peptides 14 and 16 increased FXa levels
      by two-fold to three-fold, and, at high levels, caused consumption coagulopathy.
      The TFPI-2-derived peptides explored in our previous study were found to inhibit
      the procoagulant effect induced by peptides 14 and 16. In the bleeding model,
      time to clot formation was shortened by 50% when peptide 14 or peptide 16 was
      topically applied or injected subcutaneously. In the wound-healing model, the
      wound became more vascular, and its size was reduced to one-fifth as compared
      with controls, upon 1 week of exposure to peptide 14 or peptide 16 applied
      topically or injected subcutaneously. Conclusions The putative heparanase
      procoagulant domain was identified. Peptides derived from this domain
      significantly shortened bleeding time and enhanced wound healing.

PMID- 28439968
TI  - Effects of an EP2 and EP3 Receptor Dual Agonist, ONO-8055, on a Radical
      Hysterectomy-Induced Underactive Bladder Model in Monkeys.
AB  - OBJECTIVES: The objective was to develop an underactive bladder (UAB) model in
      primates and to evaluate the potential of prostanoid EP2 and EP3 receptor dual
      agonist ONO-8055 to become a therapeutic agent for UAB. METHODS: A surgical
      procedure resembling radical hysterectomy was performed on female cynomolgus
      monkeys. Subsequently, in vitro muscle strip studies were performed using bladder
      muscle strips from normal monkeys and monkeys that underwent surgery. In
      addition, uroflowmetric data were obtained at specified days after the surgery.
      To evaluate the effects of ONO-8055 and distigmine (DIS) on voiding function in
      the UAB monkey model, uroflowmetry was performed approximately 1 week after the
      surgery, before and after the cumulative intravenous administration of the
      compounds at 2 h intervals. RESULTS: In the bladder muscle strip studies, the
      responses to potassium chloride at 2 months, and carbachol and electrical field
      stimulation from 2 weeks decreased significantly. Voided volume (VV), maximum
      flow rate (Qmax), and average flow rate (Qave) decreased after surgery, while
      voiding time (VT) increased. In this model, ONO-8055 and DIS significantly
      increased VV and Qmax. DIS prolonged VT, while ONO-8055 had no effect. The
      results also showed that ONO-8055 increased Qave. CONCLUSIONS: We developed a
      neurogenic UAB model in primates. As ONO-8055 improved voiding function in this
      model to at least the same degree as DIS, this EP2 and EP3 receptor dual agonist
      has the potential to be a candidate for neurogenic UAB pharmacotherapy.

PMID- 28439970
TI  - Dasatinib-associated follicular lymphoid hyperplasia: First pediatric case report
      and literature review.

PMID- 28439969
TI  - Factors screening to statistical experimental design of racemic atenolol kinetic
      resolution via transesterification reaction in organic solvent using free
      Pseudomonas fluorescens lipase.
AB  - As the (R)-enantiomer of racemic atenolol has no beta-blocking activity and no
      lack of side effects, switching from the racemate to the (S)-atenolol is more
      favorable. Transesterification of racemic atenolol using free enzymes
      investigated as a resource to resolve the racemate via this method is limited.
      Screenings of enzyme, medium, and acetyl donor were conducted first to give
      Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate. A statistical
      design of the experiment was then developed using Central Composite Design on
      some operational factors, which resulted in the conversions of 11.70-61.91% and
      substrate enantiomeric excess (ee) of 7.31-100%. The quadratic models are
      acceptable with R2 of 95.13% (conversion) and 89.63% (ee). The predicted values
      match the observed values reasonably well. Temperature, agitation speed, and
      substrate molar ratio factor have low effects on conversion and ee, but enzyme
      loading affects the responses highly. The interaction of temperature-agitation
      speed and temperature-substrate molar ratio show significant effects on
      conversion, while temperature-agitation speed, temperature-substrate molar ratio,
      and agitation speed-substrate molar ratio affect ee highly. Optimum conditions
      for the use of Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate
      were found at 45 degrees C, 175 rpm, 2000 U, and 1:3.6 substrate molar ratio.

PMID- 28439971
TI  - Resolution, determination of enantiomeric purity and chiral recognition mechanism
      of new xanthone derivatives on (S,S)-whelk-O1 stationary phase.
AB  - The enantioresolution and determination of the enantiomeric purity of 32 new
      xanthone derivatives, synthesized in enantiomerically pure form, were
      investigated on (S,S)-Whelk-O1 chiral stationary phase (CSP). Enantioselectivity
      and resolution (alpha and RS ) with values ranging from 1.41-6.25 and from 1.29
      17.20, respectively, were achieved. The elution was in polar organic mode with
      acetonitrile/methanol (50:50 v/v) as mobile phase and, generally, the (R)
      enantiomer was the first to elute. The enantiomeric excess (ee) for all
      synthesized xanthone derivatives was higher than 99%. All the enantiomeric pairs
      were enantioseparated, even those without an aromatic moiety linked to the
      stereogenic center. Computational studies for molecular docking were carried out
      to perform a qualitative analysis of the enantioresolution and to explore the
      chiral recognition mechanisms. The in silico results were consistent with the
      chromatographic parameters and elution orders. The interactions between the CSP
      and the xanthone derivatives involved in the chromatographic enantioseparation
      were elucidated.

PMID- 28439972
TI  - Mitochondrial biogenesis and PGC-1alpha gene expression in male broilers from
      ascites-susceptible and -resistant lines.
AB  - Ascites is a cardiovascular metabolic disease characterized by accumulation of
      fluid around the heart and in the abdominal cavity that eventually leads to
      death. This syndrome is the end-point result of a series of metabolic incidents
      that are generally caused by impaired oxygen availability. Mitochondria are the
      major sites of oxygen consumption, therefore major contributors to oxidative
      stress. Genetic, metabolic and dietary factors can influence variations in
      mitochondrial biogenesis (mitochondrial size, number and mass) that might have an
      effect on oxygen consumption and reactive oxygen species production. This study
      evaluated the effect of genotype on PGC-1alpha mRNA gene expression and
      mitochondrial biogenesis. These parameters were examined in male broiler chickens
      at 22 weeks of age from the SUS and RES lines divergently selected for ascites
      phenotype. From each line, five birds were sampled for right ventricle and breast
      muscle. Gene expression and mtDNA copy number were assessed by quantitative PCR.
      Results showed that birds from SUS had significantly higher PGC-1alpha mRNA gene
      (p = .033) and mitochondrial DNA copy number (p = .038) in breast muscle. There
      was no difference in right ventricle PGC-1alpha expression or mitochondrial DNA
      copy number between the two lines. These findings indicate that mitochondrial
      biogenesis and PGC-1alpha mRNA gene expression differ between male broiler
      chickens from RES and SUS lines in a tissue-specific manner.

PMID- 28439973
TI  - Intracardiac versus transesophageal echocardiography to guide transcatheter
      closure of interatrial communications: Nationwide trend and comparative analysis.
AB  - OBJECTIVES: This study aimed to assess current temporal trends in utilization of
      ICE versus TEE guided closure of interatrial communications, and to compare
      periprocedural complications and resource utilization between the two imaging
      modalities. BACKGROUND: While transesophageal echocardiography (TEE) has
      historically been used to guide percutaneous structural heart interventions,
      intracardiac echocardiography (ICE) is being increasingly utilized to guide many
      of these procedures such as closure of interatrial communications. METHODS: Using
      the Nationwide Inpatient Sample, all patients aged >18 years, who underwent ASD
      or PFO closure with either ICE or TEE guidance between 2003 and 2014 were
      included. Comparative analysis of outcomes and resource utilization was performed
      using a propensity score-matching model. RESULTS: ICE guidance for interatrial
      communication closure increased from 9.7% in 2003 to 50.6% in 2014. In the
      matched model, the primary endpoint of major adverse cardiovascular events
      occurred less frequently in the ICE group versus the TEE group (11.1% vs 14.3%,
      respectively, P = 0.008), mainly driven by less vascular complications in the ICE
      group (0.5% vs 1.3%, P = 0.045). Length of stay was shorter in the ICE group (3
      +/- 4 vs 4 +/- 4 days, P < 0.0001). Cost was similar in the two groups 18 454 +/-
      17 035$ in the TEE group vs 18 278 +/- 15 780$ in the ICE group (P = 0.75).
      CONCLUSIONS: Intracardiac echocardiogram utilization to guide closure of
      interatrial communications has plateaued after a rapid rise throughout the 2000s.
      When utilized to guide interatrial communication closure procedure, ICE is as
      safe as TEE and does not increase cost or prolonged hospitalizations.

PMID- 28439974
TI  - Visual and Physiological Optics: where will the journey lead us in 10 years?

PMID- 28439975
TI  - Scleral changes with accommodation.
AB  - PURPOSE: To assess whether the sclera changes its shape during accommodation,
      quantify those changes and ascertain whether they depend on age and refractive
      power. METHODS: Twenty-two subjects, aged between 19 and 84 years old were
      recruited for the study. Young subjects were grouped according to their
      refractive power as emmetropes (seven subjects) and myopes (seven subjects). Data
      were obtained with a height corneo-scleral topographer (Eye Surface Profiler)
      with coverage area far beyond the limbus. Lenses of different power were used to
      stimulate accommodative demand of 0.0 D, 2.5 D and 4.0 D. Elevation differences
      between measurements acquired while at the intermediate or close target and
      infinity where calculated for each participant for the horizontal meridian for a
      16 mm chord. RESULTS: We found that sclera undergoes significant changes in its
      shape with accommodation in young subjects able to accommodate but not for those
      with limited accommodation. For a 4.0 D stimulus at the nasal side the scleral
      change amounted on average to 390 +/- 330 MUm (mean +/- S.D.) for the young
      group. This phenomenon was more pronounced in myopes (for a 4.0 D target; nasal
      part: 560 +/- 350 MUm (mean +/- S.D.)) than emmetropes (for a 4.0 D target; nasal
      part: 220 +/- 120 MUm (mean +/- S.D.)). Differences were also found between
      different meridians. CONCLUSIONS: Scleral shape undergoes changes with
      accommodation and this phenomenon is more pronounced in myopes than emmetropes.

PMID- 28439976
TI  - Eye retraction and rotation during Corvis ST 'air puff' intraocular pressure
      measurement and its quantitative analysis.
AB  - PURPOSE: The aim of this study was to analyse the indentation and deformation of
      the corneal surface, as well as eye retraction, which occur during air puff
      intraocular pressure (IOP) measurement. METHODS: A group of 10 subjects was
      examined using a non-contact Corvis ST tonometer, which records image sequences
      of corneas deformed by an air puff. Obtained images were processed numerically in
      order to extract information about corneal deformation, indentation and eyeball
      retraction. RESULTS: The time dependency of the apex deformation/eye retraction
      ratio and the curve of dependency between apex indentation and eye retraction
      take characteristic shapes for individual subjects. It was noticed that the eye
      globes tend to rotate towards the nose in response to the air blast during
      measurement. This means that the eye globe not only displaces but also rotates
      during retraction. Some new parameters describing the shape of this curve are
      introduced. Our data show that intraocular pressure and amplitude of corneal
      indentation are inversely related (r8  = -0.83, P = 0.0029), but the correlation
      between intraocular pressure and amplitude of eye retraction is low and not
      significant (r8  = -0.24, P = 0.51). CONCLUSIONS: The curves describing corneal
      behaviour during air puff tonometry were determined and show that the eye globe
      rotates towards the nose during measurement. In addition, eye retraction
      amplitudes may be related to elastic or viscoelastic properties of deeper
      structures in the eye or behind the eye and this should be further investigated.
      Many of the proposed new parameters present comparable or even higher
      repeatability than the standard parameters provided by the Corvis ST.

PMID- 28439977
TI  - Method of locating the visual axis objectively.
AB  - PURPOSE: To locate the visual axis of the eye objectively. METHOD: Based on three
      beam scanning laser radar microprofilometry, a technique is proposed to
      objectively locate the visual axis of the eye. The laser beam consists of three
      components, two of them being shifted relatively to the central one by differing
      frequencies, filtered in spatially orthogonal directions. The centre of the
      foveola is defined as the crossing of steepest inclinations determined in the
      specific beam positions on the trajectory of scanning. The position of the cornea
      crossing by the visual axis is designated by the optical axis of the measuring
      instrument. RESULTS: Nanometer sensitivity was confirmed in a preliminary test.
      CONCLUSIONS: The proposed technique can be incorporated into any clinical
      wavefront sensing instrument and can be used for centration-sensitive vision
      correction, as well as for other instances when knowing the exact position of the
      fovea is important.

PMID- 28439978
TI  - Simulation of commercial vs theoretically optimised contact lenses for
      presbyopia.
AB  - PURPOSE: To compare theoretically optimised bifocal contact lens optical designs
      to commercially available optical designs for presbyopia. METHODS: Retinal images
      were simulated, using a numerical eye model, from -6 (i.e., near vision) to +2 D
      for each 0.25 D. Ten optical profiles were simulated. Four of them corresponded
      to commercial contact lenses (i.e., Acuvue Oasys for Presbyopia(r), Air Optix
      Aqua Multifocal(r), Purevision Multifocal(r) and Distance Biofinity
      Multifocal(r)). We also included six optimised profiles: (1) a combination of
      primary and secondary spherical aberration, (2) bifocal profiles with 2, 5 and 8
      concentric zones, and (3) a combination of spherical aberrations with the 5 and 8
      zones profiles. Twenty subjects scored the quality of vision of calculated images
      (i.e., three high-contrast 0.40 logMAR letters) for each design and vergence with
      a five-item continuous grading scale. They viewed these images through their best
      sphero-cylindrical correction and a 3-mm pupil to limit the impact of their
      aberrations. To quantify the ability of a bifocal optic to maintain a certain
      level of quality of vision, we calculated two criteria: (1) the area under the
      through-focus quality of vision curve higher than 2 (i.e., limit between poor and
      fair quality of vision) normalised by the same area calculated on the naked eye's
      curve, and (2) the width of the curve at a level of 2 (i.e., depth-of-focus).
      RESULTS: Commercial contact lens profiles did not give an image quality and depth
      of-focus as good as the theoretically optimised optical profiles. Based on these
      two criteria, the best bifocal profiles were those with 5 and 8 concentric zones.
      Important inter-individual variations were observed for all profiles. We also
      observed that some subjects did not obtain any benefit with all the designs
      whereas others seemed to be satisfied whatever the optical profiles. CONCLUSION:
      Our previously optimised designs with 5 and 8 zones gave the best benefit and
      depth-of-focus. As their image quality is better than commercially available
      designs, it would be interesting to prototype these designs and to test them in a
      clinical setting.

PMID- 28439979
TI  - Scattering contribution to the double-pass PSF using Monte Carlo simulations.
AB  - PURPOSE: Scattering in the eye occurs mainly at two sites: the eye's optical
      media and the deeper retinal layers. Although the two phenomena are often treated
      collectively, their spatial domain of contribution to the double-pass Point
      Spread Function (PSF) is different: the fundus effect is limited to the narrow
      and middle part of the PSF whereas scattering in the eye's optics extends also to
      wide angles. The objective of this work was to determine the domain of
      contribution at the double-pass PSF of light scattered in the ocular media and
      the ocular fundus, using simulated and experimental data for two different
      wavelengths and for two different pigmentations. METHODS: Diffuse reflection was
      simulated using Monte Carlo simulations for a four-layer retinal fundus model.
      Four situations were simulated in total for two different choroidal absorptions
      at two different wavelengths. Light diffusion in the fundus was the only
      phenomenon considered in the model. The simulations were compared against
      experimental fundus reflection data obtained in a previous study. RESULTS: The
      simulations showed that at 560 nm, diffusion in the fundus causes light to extend
      to a radius of 2 degrees , independently of the choroidal pigmentation, whereas
      at 650 nm it extends to radii of 4.5 degrees  and 4 degrees  for low and high
      choroidal pigmentation respectively. Experimental data showed a similar behaviour
      at low angles where light diffusion in the fundus is dominant, but different at
      higher angles due to scattering in the ocular media. CONCLUSION: The spatial
      contribution of light diffused in the ocular fundus to the PSF was found to be
      limited to narrower angles compared to that of scattering at the ocular media.
      The comparison of simulated and optical data showed that beyond 2 degrees  at 560
      nm and 4-4.5 degrees  at 650 nm the only phenomenon contributing to the PSF is
      scattering in the ocular media, whereas the fundus contribution can be assumed as
      negligible.

PMID- 28439980
TI  - Nanophotonic trapping: precise manipulation and measurement of biomolecular
      arrays.
AB  - Optical trapping is a powerful and widely used laboratory technique in the
      biological and materials sciences that enables rapid manipulation and measurement
      at the nanometer scale. However, expanding the analytical throughput of this
      technique beyond the serial capabilities of established single-trap microscope
      based optical tweezers remains a current goal in the field. In recent years,
      advances in nanotechnology have been leveraged to create innovative optical
      trapping methods that increase the number of available optical traps and permit
      parallel manipulation and measurement of arrays of optically trapped targets. In
      particular, nanophotonic trapping holds significant promise for integration with
      other lab-on-a-chip technologies to yield compact, robust analytical devices. In
      this review, we highlight progress in nanophotonic manipulation and measurement,
      as well as the potential for implementing these on-chip functionalities in
      biological research and biomedical applications. WIREs Nanomed Nanobiotechnol
      2018, 10:e1477. doi: 10.1002/wnan.1477 This article is categorized under:
      Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

PMID- 28439981
TI  - Evolution of the plasma proteome of divers before and after a single SCUBA dive.
AB  - PURPOSE: Decompression sickness (DCS) is a poorly understood and complex systemic
      disease caused by inadequate desaturation following a reduction of ambient
      pressure. A previous proteomic study of ours showed that DCS occurrence but not
      diving was associated with changes in the plasma proteome in rats, including a
      dramatic decrease of abundance of the tetrameric form of Transthyretin (TTR). The
      present study aims to assess the impact on the human blood proteome of a dive
      inducing significant decompression stress but without inducing DCS symptoms.
      EXPERIMENTAL DESIGN: Twelve healthy male divers were subjected to a single dive
      at a depth of 18 m of sea water (msw) with a 47-min bottom time followed by a
      direct ascent to the surface at a rate of 9 msw/min. Venous blood was collected
      before the dive as well as 30 min and 2 h following the dive. The plasma
      proteomes from four individuals were then analyzed by using a two-dimensional
      electrophoresis-based proteomic strategy. RESULTS: No protein spot showed a
      significantly changed abundance (fdr< 0.1) between the tested times. CONCLUSION:
      These results strengthen the hypothesis according to which significant changes of
      the plasma proteome measurable with two-dimensional electrophoresis may only
      occur along with DCS symptoms.

PMID- 28439982
TI  - Impaired endothelial function in patients with cryptogenic stroke and patent
      foramen ovale is not affected by closure.
AB  - INTRODUCTION: Patent foramen ovale (PFO) is associated with cryptogenic stroke
      (CS) and migraine with aura (MA). Endothelial dysfunction (ED) is a risk factor
      for development of cardiovascular disease, but might also be involved in migraine
      pathophysiology. Short-term worsening of migraine has been described after
      closure of PFO. We evaluated endothelial function in patients with CS and PFO,
      before and after closure of PFO, and in patients with migraine, whether changes
      in endothelial function was related to a change in migraine frequency. MATERIAL
      AND METHODS: Patients with CS and PFO were included; 20 with planned closure of
      PFO and seven controls on medical treatment only. Endothelial function was
      assessed by peripheral arterial tonometry (EndoPatR ) and biomarkers of
      endothelial activation. Patients were followed longitudinally at baseline, day 1,
      1 month, and 6 months. A headache diary was used to assess migraine frequency.
      RESULT: Mean age of the cohort was 45.4 years, and migraine prevalence was 50%
      whereof 84.6% had MA. Median EndoPatR index (RHI) at baseline was 1.60 (IQR 1.41
      2.00). There was no change in RHI over time, either in closure patients (P =
      0.66), nor in controls (P = 0.31), and there was no change in biomarkers of
      endothelial activation. Three migraine patients experienced worsening of migraine
      frequency directly after closure. DISCUSSION: Endothelial function did not change
      after closure of PFO. Although patients were lacking cardiovascular risk factors,
      a high proportion had impaired endothelial function. Whether ED can have
      predictive value, identifying PFO at higher risk for recurrent stroke warrants
      further investigations.

PMID- 28439983
TI  - A method for assessing the performance of nanofiber films coated on window
      screens in reducing residential exposures to PM2.5 of outdoor origin in Beijing.
AB  - Recently, many nanofiber films have been developed for air filtration
      applications. These films exhibit high PM2.5 (particles with aerodynamic
      diameters less than 2.5 MUm) removal efficiency and relatively low air
      resistance. Thus, coating window screens with nanofiber films may be able to
      mitigate residential exposure to PM2.5 of outdoor origin. This study developed a
      method for assessing the performance of nanofiber window screens in reducing
      residential exposure to PM2.5 of outdoor origin in Beijing. The results show that
      the use of selected nanofiber window screens all the time throughout the year can
      reduce the mean value of the annual average indoor PM2.5 of outdoor origin by 64%
      66% for Beijing residences. However, the mean value of annual harmonic average
      air exchange rate when the windows are open was also reduced from 2.34 h-1 to
      0.27-0.35 h-1 , which is far below the national standard. If the nanofiber window
      screens were used only when the outdoor PM2.5 pollution was severe, the screens
      had less of an impact on residential natural ventilation, but the national
      standard still could not be met. Hence, more efforts are needed to further reduce
      the air resistance of nanofiber window screens in order to ensure proper
      residential ventilation.

PMID- 28439984
TI  - Effects of energy supply and nicotinic acid supplementation on serum anti
      oxidative capacity and on expression of oxidative stress-related genes in blood
      leucocytes of periparturient primi- and pluriparous dairy cows.
AB  - The periparturient period is accompanied by metabolic and oxidative stress.
      Niacin is known to decrease lipolysis but is also reported to have anti-oxidative
      effects. Therefore, we examined the effects of energy supply and a nicotinic acid
      (NA) supplementation on anti-oxidative serum parameters and on the expression of
      oxidative stress-related genes in blood leucocytes of periparturient dairy cows,
      differing in parity. Twenty-nine pluriparous and 18 primiparous cows were
      allocated to four different feeding groups 42 days before expected parturition
      until 100 days postpartum and fed a ration with either a low concentrate
      proportion of 30% (LC) or a high concentrate proportion of 60% (HC). After
      parturition, all animals received 30% concentrate which was increased to 50%
      either within 16 (LC group) or 24 days (HC group). Half of the animals per group
      were supplemented with 24 g NA per day from 42 days prepartum until 24 days
      postpartum. All investigated parameters varied significantly over time compared
      to parturition (p < .05). Ferric reducing ability (FRA) exhibited a nadir before
      parturition, and the antioxidant enzymes glutathione peroxidase (GPX) and
      superoxide dismutase (SOD) showed peak activities around parturition. Expression
      levels of GPX1, SOD2, xanthine dehydrogenase (XDH) and nuclear factor (erythroid
      derived 2)-like 2 (NRF2) peaked before calving. The concentrate level influenced
      GPX activity and mRNA abundance of SOD2, XDH and poly (ADP-ribose) polymerase 1
      (PARP1). Pluriparous animals exhibited higher serum GPX activities, a more
      distinct nadir for FRA and higher expression levels for GPX1, SOD2 and XDH.
      Primiparous cows displayed higher serum SOD activities. NA supplementation
      increased serum SOD activity antepartum in LC animals. Parturition was
      characterised by an increased need for antioxidants and an increased expression
      of oxidative stress-related genes that clearly differed with parity and was
      influenced by energy supply while NA exerted only minor effects on the
      investigated parameters.

PMID- 28439985
TI  - The utility of MASS-FIX to detect and monitor monoclonal proteins in the clinic.
AB  - The detection and quantification of monoclonal-proteins (M-proteins) are
      necessary for the diagnosis and evaluation of response in plasma cell dyscrasias.
      Immunoglobulin enrichment-coupled with matrix-assisted laser desorption
      ionization time-of-flight mass-spectrometry (MASS-FIX) is a simple and
      inexpensive method to identify M-proteins, but its clinical generalizability has
      not yet been elucidated. We compared MASS-FIX to protein electrophoresis (PEL),
      serum/urine immunofixation-electrophoresis (IFE), and quantitative serum free
      light chain (FLC) for the identification of M-proteins in different clinical
      diagnoses. Paired serum and urine samples from 257 patients were tested. There
      were six patients for whom s-IFE and FLC ratio were positive and serum MASS-FIX
      was negative, but when serum and urine MASS-FIX results were combined, only one
      patient with light chain-MGUS was missed. Serum/urine-MASS-FIX detected M
      proteins in 18 patients with negative serum/urine-PEL/IFE and serum-FLC, 10 of
      whom had multiple myeloma or AL amyloidosis, who were mistakenly thought to have
      complete hematologic response by serum/urine-PEL/IFE and serum-FLC. Nearly half
      of the AL amyloidosis patients had atypical spectra, which may prove to be a clue
      to the diagnosis and pathogenesis of the disease. In conclusion, MASS-FIX has a
      comparable sensitivity with PEL/IFE/FLC methods and can help inform the clinical
      diagnosis.

PMID- 28439986
TI  - Coordinated Membrane Fusion of Proteinosomes by Contact-Induced Hydrogel Self
      Healing.
AB  - Controlled membrane fusion of proteinosome-based protocells is achieved via a
      hydrogel-mediated process involving dynamic covalent binding, self-healing, and
      membrane reconfiguration at the contact interface. The rate of proteinosome
      fusion is dependent on dynamic Schiff base covalent interchange, and is
      accelerated in the presence of encapsulated glucose oxidase and glucose, or
      inhibited with cinnamyl aldehyde due to enzyme-mediated decreases in pH or
      competitive covalent binding, respectively. The coordinated fusion of the
      proteinosomes leads to the concomitant transportation and redistribution of
      entrapped payloads such as DNA and dextran. Silica colloids with amino
      functionalized surfaces undergo partial fusion with the proteinosomes via a
      similar dynamic hydrogel-mediated mechanism. Overall, the strategy provides
      opportunities for the development of interacting colloidal objects, control of
      collective behavior in soft matter microcompartmentalized systems, and increased
      complexity in synthetic protocell communities.

PMID- 28439987
TI  - Comparison of Silodosin versus Tadalafil in Patients with Lower Urinary Tract
      Symptoms Associated with Benign Prostatic Hyperplasia.
AB  - OBJECTIVES: To compare the efficacy and safety of silodosin versus tadalafil for
      treating lower urinary tract symptoms associated with benign prostatic
      hyperplasia (LUTS/BPH). METHODS: After informed consent, patients with LUTS/BPH
      were randomized in a 1:1 ratio to receive silodosin 8 mg/day or tadalafil 5
      mg/day for 8 weeks (Period 1). Patients treated with tadalafil entered an
      exploratory phase and received silodosin or tadalafil for another 8 weeks. The
      primary efficacy endpoint was the change in the total International Prostate
      Symptom Score (IPSS) with Period 1 treatment. RESULTS: Both silodosin and
      tadalafil demonstrated statistically significant improvement in IPSS total
      symptom score, with a mean +/- standard deviation change of -10.1 +/- 6.4 (P <
      0.0001) and -8.0 +/- 6.3 (P < 0.0001), respectively. The former reduction was
      significantly greater than the latter (P = 0.0277). Adverse drug reactions
      occurred at a rate of 23.4% with silodosin and 8.4% with tadalafil. No serious
      adverse drug reactions were documented, suggesting that both drugs were well
      tolerated. Moreover, results of Period 2 showed that switching to silodosin from
      tadalafil achieved a faster onset of improvements in IPSS Quality of Life Index
      score and total Overactive Bladder Symptom Score. CONCLUSIONS: Silodosin achieved
      significantly greater improvement than tadalafil, with a higher incidence of
      adverse drug reactions. The risk-benefit profiles obtained in this study will
      provide useful information for optimal pharmacological treatment of LUTS/BPH. Our
      results suggest that silodosin can be one of the first-line therapies for rapid
      and efficient relief in patients with LUTS/BPH.

PMID- 28439988
TI  - Reply to "Rigor, reproducibility and in vitro CSF assays: The devil in the
      details".

PMID- 28439989
TI  - Using size-controlled multicellular spheroids of murine adenocarcinoma cells to
      efficiently establish pulmonary tumors in mice.
AB  - Previous studies demonstrated that multicellular spheroids developed using
      polydimethylsiloxane-based microwells exhibited superior functions, such as
      insulin secretion from pancreatic cells, over suspended cells. To successfully
      apply these spheroids, the effect of spheroid size on cellular functions must be
      determined. In this study, using murine adenocarcinoma colon26 cells, the authors
      examined whether such spheroids were useful for developing tumor-bearing animal
      models, which requires the efficient and stable engraftment of cancer cells at
      implanted sites and/or metastatic sites. The authors prepared microwells with
      widths of 360, 450, 560, and 770 MUm through a micromolding technique, and
      obtained colon26 spheroids with average diameters of 169, 240, 272, and 341 MUm,
      respectively. Small and medium spheroids were subsequently used. mRNA levels of
      integrin beta1, CD44, and fibronectin, molecules involved in cell adhesion,
      increased with increasing colon26 spheroid size. Approximately 1.5 * 104 colon26
      cells in suspension or in spheroids were intravenously inoculated into BALB/c
      mice. At 21 days after inoculation, the lung weight of both colon26 spheroid
      groups, especially the group injected with small spheroids, was significantly
      higher than that of mice in the suspended colon26 cell group. These results
      indicate that controlling cancer cell spheroid size is crucial for tumor
      development in tumor-bearing mouse models.

PMID- 28439990
TI  - Explaining the declining rates of past year cannabis use in Australia: A first
      pass.
AB  - INTRODUCTION AND AIMS: Cannabis use rates in Australia have declined since 2001.
      No research to date has examined possible reasons, despite evident policy
      interest in understanding such a positive public health outcome. In a 'first
      pass' examination, five possible reasons are explored: (i) attitudinal shifts
      regarding the acceptability of cannabis use; (ii) regulatory or policy changes;
      (iii) supply/market changes; (iv) changes in other drug use that may operate as
      substitutes or complements to cannabis; and (v) socio-cultural factors. METHODS:
      Secondary analyses from three publically available national surveys (the National
      Drug Strategy Household Survey 2001 to 2013, the Illicit Drug Reporting System
      2004 to 2013 and the Illicit Drug Data Report 2002 to 2013) were used to explore
      the five reasons. RESULTS: It appears that all five explanations are reasonable
      and have preliminary evidence to indicate they are worth pursuing empirically.
      Attitudes have not softened towards cannabis in Australia, and regulatory changes
      appear to have tightened. Perceived purity may have declined, and with stable
      prices, this suggests an increase in purity-adjusted price that would also be
      consistent with decreased use. The significant declines in tobacco and alcohol
      use in Australia, which operate as complements to cannabis, also plausibly
      account for the significant decrease. DISCUSSION AND CONCLUSIONS: This work
      suggests future directions for cannabis research in Australia. New multi
      disciplinary research that has the potential to explore multiple hypotheses
      simultaneously is required. [Ritter A, Sotade O. Explaining the declining rates
      of past year cannabis use in Australia: A first pass. Drug Alcohol Rev
      2017;00:000-000].

PMID- 28439991
TI  - Melatonin: A pleiotropic molecule that modulates DNA damage response and repair
      pathways.
AB  - DNA repair is responsible for maintaining the integrity of the genome.
      Perturbations in the DNA repair pathways have been identified in several human
      cancers. Thus, compounds targeting DNA damage response (DDR) hold great promise
      in cancer therapy. A great deal of effort, in pursuit of new anticancer drugs,
      has been devoted to understanding the basic mechanisms and functions of the
      cellular DNA repair machinery. Melatonin, a widely produced indoleamine in all
      organisms, is associated with a reduced risk of cancer and has multiple
      regulatory roles on the different aspects of the DDR and DNA repair. Herein, we
      have mainly discussed how defective components in different DNA repair
      machineries, including homologous recombination (HR), nonhomologous end-joining
      (NHEJ), base excision repair (BER), nucleotide excision repair (NER), and finally
      DNA mismatch repair (MMR), can contribute to the risk of cancer. Melatonin
      biosynthesis, mode of action, and antioxidant effects are reviewed along with the
      means by which the indoleamine regulates DDR at the transduction, mediation, and
      functional levels. Finally, we summarize recent studies that illustrate how
      melatonin can be combined with DNA-damaging agents to improve their efficacy in
      cancer therapy.

PMID- 28439992
TI  - The Construction of Homochiral Lanthanide Quadruple-Stranded Helicates with
      Multiresponsive Sensing Properties toward Fluoride Anions.
AB  - A series of unique homochiral lanthanide tetranuclear quadruple-stranded
      helicates have been self-assembled controllably by using the intrinsic advantages
      of chiral bridging ligands, (S)-H2 L and (R)-H2 L, and lanthanide ions with high
      coordination numbers. The self-assembly process of these chiral helicates not
      only ensures the structural stability and quadruple-stranded feature of
      lanthanide cluster in the solid state and solution, but also achieves effective
      transfer and amplification of the chirality code from the ligand to a higher
      supramolecular level. Moreover, through using optical rotation, circular
      dichroism spectra analysis, and luminescence measurements, we demonstrate that
      these chiral lanthanide helicates could serve as sensitive and multi-responsive
      sensors to recognize and detect F- anions based on the change of chiral signal
      and NIR luminescence simultaneously, which represents a meaningful exploration
      for developing functional lanthanide-based polynuclear clusters.

PMID- 28439994
TI  - Ethnicity and age as factors in sildenafil treatment of erectile dysfunction.
AB  - INTRODUCTION: Sildenafil has been evaluated in >16 000 men with erectile
      dysfunction (ED) in double-blind, placebo-controlled trials. AIM: To assess
      efficacy and safety of sildenafil in ED by ethnicity (white, black Asian) and age
      (<=45, 46-60, >=61 years). METHODS: Data were pooled from 38 double-blind,
      placebo-controlled, flexible-dose trials. Most had starting sildenafil doses of
      50 mg once daily, ~1 hour before sexual activity, with adjustment to 100 or 25 mg
      as needed. MAIN OUTCOME MEASURES: Change from baseline in International Index of
      Erectile Function erectile function (IIEF-EF) domain score assessed with analysis
      of covariance and a Global Assessment Question (GAQ; "Did the treatment improve
      your erections?") at endpoint assessed with logistic regression analysis.
      RESULTS: 4120 and 3714 men received sildenafil and placebo, respectively (2740
      and 2671 White; 407 and 385 Black; 973 and 658 Asian). For sildenafil vs. placebo
      groups, overall treatment differences for IIEF-EF domain and GAQ were significant
      for each ethnic and age group (P<.0001); significant treatment-by-ethnicity and
      treatment-by-age interactions were also observed for change in IIEF-EF domain
      scores (P<.05), with differences significantly greater for White vs. Black
      (P<.0001), White vs. Asian (P=.0163), and Asian vs. Black (P=.0036) men. A
      significant treatment-by-ethnicity interaction was observed for GAQ (P=.0004).
      The OR comparison for GAQ was significantly greater (P=.0001) with sildenafil vs.
      placebo in White (OR=11.2) or Asian (OR=12.4) men vs. Black men (OR=5.1). Adverse
      event rates were generally similar, with some age variations. CONCLUSIONS:
      Sildenafil is effective and well-tolerated regardless of ethnicity or age;
      however, treatment effects can vary.

PMID- 28439993
TI  - Non-smoker assertive behaviour against smoke exposure: Chinese and Korean
      American non-smokers.
AB  - INTRODUCTION AND AIMS: Non-smokers' assertive behaviour towards smokers by asking
      them not to smoke is important in promoting smoke-free environments. Korean and
      Chinese Americans come from countries where most women are non-smokers and
      assertive behaviour may not be prevalent but may increase after migration because
      of social-ecological factors. This study assessed the extent to which Korean and
      Chinese American non-smokers ask someone not to smoke and associated factors.
      DESIGN AND METHODS: The 2003 California Chinese American and Korean American
      Tobacco Use Surveys were analysed. Multivariate logistic regression analyses
      examined factors related to non-smoker self-reports that they asked someone not
      to smoke within the past year. RESULTS: About 40% reported past-year assertive
      behaviour against smoking, with higher rates among Koreans than Chinese (60.4%
      vs. 34.5%), those living with smokers (63.5%), ever exposed with a smoke-free
      home rule (62.3%), recently exposed at work without a smoke-free work policy
      (67.6%) and regularly exposed at other locations (52.3%). In combined
      multivariate analyses of both ethnic groups, assertive behaviour was associated
      with individual factors (single vs. married; tobacco exposure knowledge), family
      factors (living with smokers, exposed at home despite a smoke-free rule),
      community factors (exposed at work with no smoke-free policy, exposed at other
      locations) and cultural factors (Korean vs. Chinese ethnicity; lower
      acculturation). DISCUSSION AND CONCLUSIONS: Chinese and Korean American non
      smokers report assertive behaviour against smoking, which is associated with
      social-ecological factors. Results help identify target groups and strategies for
      future intervention, including the need to implement or enforce smoke-free
      environments and promote empowerment. [Saw A, Tang H, Tsoh JY, Chen MS Jr, Tong
      EK. Non-smoker assertive behaviour against smoke exposure: Chinese and Korean
      American non-smokers.

PMID- 28439995
TI  - Scleromyxoedema in a dog.
AB  - BACKGROUND: In humans, scleromyxoedema is a chronic progressive skin condition
      traditionally characterized by deposits of mucin, increased number of fibroblasts
      and fibrosis in the skin, and by systemic disease. Thyroid disease is typically
      absent. A monoclonal gammopathy is usually present, as are other comorbidities.
      Descriptions of scleromyxoedema in the veterinary literature are limited to a
      single feline case. One dog, previously reported as having papular mucinosis,
      exhibited features that matched the more current diagnostic criteria of
      scleromyxoedema. OBJECTIVES: To describe generalized papular mucinosis in a dog
      with systemic illness and to compare the signs with those of human lichen
      myxoedematosus conditions, specifically scleromyxoedema. RESULTS: A nine-year-old
      female, spayed English springer spaniel dog presented with generalized papules
      and nodules (0.5-5 cm) on the body and proximal fore and hind limbs, sparing the
      face and distal limbs distal to carpi/tarsi. Larger nodules were erythematous.
      Nodules occurred in proximal limb muscles. The dog had concurrent osteoarthritis
      of the elbows and coxofemoral joints, developed generalized weakness, declined in
      health and was euthanized. Thyroid disease was lacking and a monoclonal
      gammopathy was not present. Histopathological evaluation revealed the classic
      triad of mucin, fibroblast proliferation and fibrosis with very mild
      inflammation, as described for humans. CONCLUSION AND CLINICAL IMPORTANCE: We
      document scleromyxoedema in a dog with significant morbidity and features of the
      human disease. Recognizing the typical histopathology is important for
      identifying cases and to establish a diagnosis. Systemic evaluation is important
      to identify evidence of internal disease and associated comorbidities, which are
      common, variable, and impact classification and prognosis in humans.

PMID- 28439996
TI  - Energy dispersive spectroscopy-scanning transmission electron microscope
      observations of free radical production in human polymorphonuclear leukocytes
      phagocytosing non-opsonized Tannerella forsythia.
AB  - We investigated the association between human polymorphonuclear leukocytes (PMNs)
      and non-opsonized Tannerella forsythia ATCC 43037 displaying a serum-resistant
      surface layer (S-layer). When PMNs were mixed with T. forsythia in suspension,
      the cells phagocytosed T. forsythia cells. Nitro blue tetrazolium (NBT)
      reduction, indicative of O2- production, was observed by light microscopy; cerium
      (Ce) perhydroxide deposition, indicative of H2 O2 production, was observed by
      electron microscopy. We examined the relationship between high-molecular-weight
      proteins of the S-layer and Ce reaction (for T. forsythia phagocytosis) using
      electron microscopic immunolabeling. Immunogold particles were localized within
      the PMNs and on cell surfaces, labelling at the same Ce-reacted sites where the S
      layer was present. We then used energy dispersive spectroscopy (EDS)-scanning
      transmission electron microscope (STEM) to perform Ce and nitrogen (N) (for S
      layer immunocytochemistry) elemental analysis on the phagocytosed cells. That is,
      the elemental mapping and analysis of N by EDS appeared to reflect the presence
      of the same moieties detected by the 3,3'-diaminobenzidine-tetrahydrochloride
      (DAB) reaction with horseradish peroxidase (HRP)-conjugated secondary antibodies,
      instead of immunogold labeling. We focused on the use of EDS-STEM to visualize
      the presence of N resulting from the DAB reaction. In a parallel set of
      experiments, we used EDS-STEM to perform Ce and gold (Au; from immunogold
      labeling of the S-layer) elemental analysis on the same phagocytosing cells.

PMID- 28439997
TI  - Therapeutic effectiveness of calcineurin inhibitors in canine vesicular cutaneous
      lupus erythematosus.
AB  - BACKGROUND: Oral and topical calcineurin inhibitors (CIs) have been reported to
      lead to complete lesion remission in several dogs with vesicular cutaneous lupus
      erythematosus (VCLE). OBJECTIVES: To report retrospectively on the effectiveness
      and adverse effects of systemic (ciclosporin) and/or topical
      (tacrolimus/pimecrolimus) CIs in 11 dogs with VCLE. METHODS: Inclusion criteria
      were: (i) presence of characteristic annular, polycyclic or serpiginous
      ulcerations distributed over the groin, axillae and/or ventral abdomen; (ii) a
      histopathological diagnosis of VCLE (i.e. a lymphocyte-rich interface dermatitis
      with vesiculation); (iii) treatment that included CIs for at least eight weeks;
      and (iv) follow-up until death/euthanasia or for a minimum of 12 months post
      diagnosis. RESULTS: Initial therapy included the avoidance of excessive sun
      exposure, oral glucocorticoids [six of 11 dogs (55%); progressively tapered over
      a month] and once daily ciclosporin [11 dogs (100%); median 5.8 mg/kg]. A
      complete remission (CR) of signs occurred between days 35 and 70 after starting
      CIs in eight dogs (73%); increasing ciclosporin dosage and adding topical
      tacrolimus induced a CR in two additional dogs (18%). Relapses were common when
      doses were tapered or discontinued. With the exception of three dogs that were
      euthanized, clinical signs were maintained in CR with oral ciclosporin (eight of
      eight dogs treated, 100%) or topical tacrolimus/pimecrolimus (four of eight dogs;
      50%) with a median follow-up of 2.9 years. CONCLUSIONS AND CLINICAL IMPORTANCE:
      These observations support CIs as the preferable therapeutic alternatives to long
      term immunosuppression with oral glucocorticoids in dogs with VCLE.

PMID- 28439998
TI  - The effects of chosen plant extracts and compounds on mesenchymal stem cells-a
      bridge between molecular nutrition and regenerative medicine- concise review.
AB  - Mesenchymal stem cells (MSC) stand as a promising tool in regenerative medicine
      because of their high therapeutic potential in treatment of degenerative,
      metabolic and other types of diseases. The cellular therapies involving MSCs
      include their isolation mainly from the bone marrow, adipose tissue or umbilical
      cord and in vitro expansion for further autologous or allogeneic transplantation.
      Recent studies revealed, that bioactive compounds, naturally occurring in
      seaweeds, herbs, fruits and vegetables, possess the ability to modulate self
      renewal and differentiation potential of adult stem cells, targeting a broad
      range of intracellular signal transduction pathways. Number of ongoing trials aim
      to find a herbal extract that may become less toxic and affordable natural
      therapeutic. Mesenchymal stem cells are treated with crude extracts or individual
      compounds to investigate its effects and mechanism on stem cells proliferation
      and differentiation. Deeply investigated, herbal extract which increases tissue
      regeneration and promotes stem cell growth may be successfully applied in the
      field of biomaterials. Promoting the endogenous stem cell multipotency and their
      differentiation potential may additionally support the regenerative processes
      after MSCs transplantation. The review focuses on the beneficial effects of
      chosen plant derived substances on MSCs proliferative activity and their
      osteogenic differentiation potential. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28439999
TI  - Cost-effectiveness of introducing a nursing-based programme of ultrasound-guided
      peripheral venous access in a regional teaching hospital.
AB  - AIM: To analyse the cost-effectiveness of care provided to patients in need of
      peripheral venous access by comparing the traditional approach with a nurse-based
      ultrasound-guided programme. BACKGROUND: Letting nurses insert ultrasound-guided
      catheters is a promising cost-saving approach, but there are few data available
      to document the efficiency of this type of programme. METHOD: A cost-efficiency
      evaluative research design was used. Data were collected over a 6-year timeframe,
      before and after the implementation of the nurse-based programme. RESULTS:
      Results show that the evaluation conducted by nurses ensures the right choice of
      catheter for each patient based on the patient's needs, which decreases costs.
      The programme also shortens the waiting period between consultation and insertion
      of the catheter, which reduces costs related to prolonged hospitalisation.
      CONCLUSION: The nurse-based programme puts nurses' skills to good use as part of
      a new practice and helps enhance the efficiency of care and services provided to
      patients. IMPLICATIONS FOR NURSING MANAGEMENT: In addition to the significant
      cost savings this programme offers, the evaluation leads to an effective use of
      resources while ensuring optimal care.

PMID- 28440000
TI  - Human symptom responses to bioeffluents, short-chain carbonyls/acids, and long
      chain carbonyls in a simulated aircraft cabin environment.
AB  - Occupants of aircraft have reported an array of symptoms related to general
      discomfort and irritation. Volatile organic compounds (VOCs) have been suggested
      to contribute to the reported symptoms. VOCs are from products used, bioeffluents
      from people and oxidation reaction products. Thirty-six healthy, young female
      subjects rated symptoms and environmental quality during an eight-hour exposure
      to groups of compounds often present in aircraft: (i) long-chain carbonyls, (ii)
      simulated bioeffluents, and (iii) short-chain carbonyls/organic acids.
      Statistically more symptoms were identified for the simulated bioeffluents and,
      to a lesser extent, short-chain carbonyls/organic acids compared to a control
      condition, although they remained in the acceptable range. There were three
      temporal patterns in the environmental quality and symptom reports: (i) an
      adaptive response (immediate increases followed by a decline); (ii) an apparent
      physiological effect (increases one to three hours into the exposure that
      remained elevated); and (iii) no statistical differences in reported
      environmental quality or symptom severity compared to the control air conditions.
      Typical concentrations found in aircraft can cause transitory symptoms in healthy
      individuals questioning the adequacy of current standards. Understanding the
      effects on individuals sensitive to air pollutants and methods to remove the
      compounds causing the greatest symptom responses are needed.

PMID- 28440001
TI  - Treating low back pain with combined cerebral and peripheral electrical
      stimulation: A randomized, double-blind, factorial clinical trial.
AB  - BACKGROUND: Recent evidence suggests that chronic low back pain is associated
      with plastic changes in the brain that can be modified by neuromodulation
      strategies. This study investigated the efficacy of transcranial direct current
      stimulation (tDCS) combined simultaneously with peripheral electrical stimulation
      (PES) for pain relief, disability and global perception in patients with chronic
      low back pain (CLBP). METHODS: Ninety-two patients with CLBP were randomized to
      receive 12 sessions on nonconsecutive days of anodal tDCS (primary motor cortex,
      M1), 100 Hz sensory PES (lumbar spine), tDCS + PES or sham tDCS + PES. Pain
      intensity (11-point numerical rating scale), disability and global perception
      were applied before treatment and four weeks, three months and six months post
      randomization. RESULTS: A two points reduction was achieved only by the tDCS +
      PES (mean reduction [MR] = -2.6, CI95% = -4.4 to -0.9) and PES alone (MR = -2.2,
      CI95% = -3.9 to -0.4) compared with the sham group, but not of tDCS alone (MR = 
      1.7, CI95% = -3.4 to -0.0). In addition to maintaining the analgesic effect for
      up to three months, tDCS + PES had a higher proportion of respondents in
      different cutoff points. Global perception was improved at four weeks and
      maintained three months after treatment only with tDCS + PES. None of the
      treatments improved disability and the affective aspect of pain consistently with
      pain reduction. CONCLUSION: The results suggest that tDCS + PES and PES alone are
      effective in relieving CLBP in the short term. However, only tDCS + PES induced a
      long-lasting analgesic effect. tDCS alone showed no clinical meaningful pain
      relief. SIGNIFICANCE: Transcranial direct current stimulation combined
      simultaneously with PES leads to a significant and clinical pain relief that can
      last up to three months in chronic low back pain patients. For this article, a
      commentary is available at the Wiley Online Library.

PMID- 28440002
TI  - Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and
      hyperalgesia in human surrogate models of neurogenic pain.
AB  - BACKGROUND: The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in
      human pain models is very divergent. This study was conducted to clarify if the
      pain models or the route of BoNT/A application might be responsible for these
      divergent findings. METHODS: Sixteen healthy subjects (8 males, mean age 27 +/- 5
      years) were included in a first set of experiments consisting of three visits:
      (1) Visit: Quantitative sensory testing (QST) was performed before and after
      intradermal capsaicin injection (CAPS, 15 MUg) on one thigh and electrical
      current stimulation (ES, 1 Hz) on the contralateral thigh. During stimulation
      pain and the neurogenic flare response (laser-Doppler imaging) were assessed. (2)
      Four weeks later, BoNT/A (Xeomin(r) , 25 MU) was injected intracutaneously on
      both sides. (3) Seven days later, the area of BoNT/A application was determined
      by the iodine-starch staining and the procedure of the (1) visit was exactly
      repeated. In consequence of these results, 8 healthy subjects (4 males, mean age
      26 +/- 3 years) were included into a second set of experiments. The experimental
      setting was exactly the same with the exception that stimulation frequency of ES
      was increased to 4 Hz and BoNT/A was injected subcutaneously into the thigh,
      which was stimulated by capsaicin. RESULTS: BoNT/A reduced the 1 Hz ES flare size
      (p < 0.001) and pain ratings (p < 0.01), but had no effect on 4 Hz ES and
      capsaicin-induced pain, hyperalgesia, or flare size, regardless of the depth of
      BoNT/A injection (i.c./s.c). Moreover, i.c. BoNT/A injection significantly
      increased warm detection and heat pain thresholds in naive skin (WDT, Delta 2.2 
      degrees C, p < 0.001; HPT Delta 1.8  degrees C, p < 0.005). CONCLUSION: BoNT/A
      has a moderate inhibitory effect on peptidergic and thermal C-fibers in healthy
      human skin. SIGNIFICANCE: The study demonstrates that BoNT/A (Incobotulinumtoxin
      A) has differential effects in human pain models: It reduces the neurogenic flare
      and had a moderate analgesic effects in low frequency but not high frequency
      current stimulation of cutaneous afferent fibers at C-fiber strength; BoNT/A had
      no effect in capsaicin-induced (CAPS) neurogenic flare or pain, or on
      hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous
      BoNT/A increases warm and heat pain thresholds on naive skin.

PMID- 28440003
TI  - Advanced SERS Sensor Based on Capillarity-Assisted Preconcentration through Gold
      Nanoparticle-Decorated Porous Nanorods.
AB  - A preconcentrating surface-enhanced Raman scattering (SERS) sensor for the
      analysis of liquid-soaked tissue, tiny liquid droplets and thin liquid films
      without the necessity to collect the analyte is reported. The SERS sensor is
      based on a block-copolymer membrane containing a spongy-continuous pore system.
      The sensor's upper side is an array of porous nanorods having tips functionalized
      with Au nanoparticles. Capillarity in combination with directional evaporation
      drives the analyte solution in contact with the flat yet nanoporous underside of
      the SERS sensor through the continuous nanopore system toward the nanorod tips
      where non-volatile components of the analyte solution precipitate at the Au
      nanoparticles. The nanorod architecture increases the sensor surface in the
      detection volume and facilitates analyte preconcentration driven by directional
      solvent evaporation. The model analyte 5,5'-dithiobis(2-nitrobenzoic acid) can be
      detected in a 1 * 10-3 m solution ~300 ms after the sensor is brought into
      contact with the solution. Moreover, a sensitivity of 0.1 ppm for the detection
      of the dissolved model analyte is achieved.

PMID- 28440004
TI  - Safety and effectiveness of room temperature stable recombinant factor VIIa in
      patients with haemophilia A or B and inhibitors: Results of a multinational,
      prospective, observational study.
AB  - INTRODUCTION: A room temperature stable formulation of recombinant activated
      factor VII (NovoSeven(r) ), allowing convenient storage and therefore improved
      treatment access, has been developed. Bioequivalence to the previous NovoSeven(r)
      was demonstrated in healthy humans, leading to European approval (2008). Although
      no confirmed cases of neutralising antibodies to rFVIIa in patients with
      haemophilia A or B have been observed with the original formulation, changes in
      formulation or storage condition may alter immunogenicity. AIM: SMART-7TM was
      designed to investigate the safety of NovoSeven(r) in a real-world setting in
      patients with haemophilia A or B with inhibitors. METHODS: Study medication was
      not provided by the sponsor, and treatment was at the discretion of the treating
      physician, in accordance with the local label. Patient baseline information was
      collected at enrolment. Information on safety, drug exposure and bleeding
      episodes was collected and FVII antibody screening was encouraged at baseline and
      performed at the investigator's discretion. RESULTS: Fifty-one patients were
      enrolled and 31 completed the study. Forty-one adverse events (AEs) were reported
      in 23 patients; 25 AEs in 14 patients were serious. No thromboembolic events were
      observed. Although four cases of reduced therapeutic response were reported, FVII
      antibody screening was negative. Forty-eight patients experienced 618 bleeding
      episodes and 93.4% of 609 evaluated bleeds were stopped by treatment. Of the 538
      bleeding episodes treated with NovoSeven(r) monotherapy, 94.2% stopped by end of
      treatment. CONCLUSION: Data collected during the SMART-7TM study revealed no
      treatment-related safety issues and no FVII-binding antibodies for patients
      treated with NovoSeven(r) under real-world conditions.

PMID- 28440005
TI  - Comparing the burden of illness of haemophilia between resource-constrained and
      unconstrained countries: the Sao Paulo-Toronto Hemophilia Study.
AB  - INTRODUCTION: Although the regular replacement of clotting factor concentrates
      (prophylaxis) has been well established as the standard of care for severe
      haemophilia, the high cost of factor concentrates has limited access to
      prophylaxis in countries with under-developed or developing economies. AIMS: We
      studied the health gap that could be addressed by providing unlimited access to
      clotting factor concentrates with implementation of long-term prophylaxis
      initiated from an early age in life. METHODS: We performed a cross-sectional
      study of a random, representative sample of boys with moderate and severe
      haemophilia at three haemophilia treatment centres in Sao Paulo, Brazil, and one
      centre in Toronto, Canada. RESULTS: Canadian subjects were more often treated
      with prophylaxis, and began treatment at an earlier age. Fewer Canadian subjects
      had bleeds within the preceding 6 months (19 vs. 34, P = 0.003). Canadian
      subjects had lower (better) Pettersson radiographic scores (1.5 vs. 6.0, P =
      0.0016), lower (better) Hemophilia Joint Health Scores (5.5 vs. 10.5, P =
      0.0038), higher (better) Activity Scale for Kids scores (96.6 vs. 92.0, P =
      0.033), more time spent in vigorous activity, and higher (better) social
      participation scores. CONCLUSIONS: Our findings suggest that increasing access to
      clotting factor concentrates for young boys with severe haemophilia is a global
      imperative.

PMID- 28440006
TI  - Health information practice: integrating, inspiring and innovating.
AB  - The 2017 virtual issue of the Health Information and Libraries Journal (HILJ) is
      published to link to the 12th International Congress on Medical Librarianship and
      the 2017 EAHIL Workshop taking place in Dublin, Ireland on 12-16 June 2017. The
      conference title is Diversity in Practice: integrating, inspiring and innovative
      and it is exploring how health science librarianship, in all its diversity, is
      integrating, inspiring and innovating practice. These themes have been used to
      compile this virtual issue, which contains published articles selected from HILJ
      from the June 2014 issue through to September 2016. The virtual issue mirrors the
      format of a regular issue of HILJ, namely a review article, six original articles
      and our three regular features: 'Dissertations into Practice', 'International
      Perspectives and Initiatives' and 'Teaching and Learning in Action'. All articles
      included in this virtual issue are available free online.

PMID- 28440007
TI  - Spectrophotometric analysis of fluorescent zirconia abutments compared to
      "conventional" zirconia abutments: A within subject controlled clinical trial.
AB  - BACKGROUND: Zirconia abutments are frequently used for implant-supported single
      crowns. Even though demonstrating esthetic benefits compared to metal abutments,
      zirconia abutments lead to an increased brightness of the peri-implant mucosa
      compared to natural teeth and are not ideal from an esthetic point of view.
      PURPOSE: To test whether or not a fluorescent hybrid zirconia abutment offers
      superior esthetics compared to a non-fluorescent one-piece zirconia abutment
      based on spectrophotometric analysis. MATERIALS AND METHODS: In 24 patients with
      24 single-tooth implants, 2 types of reconstructions were fabricated: a directly
      veneered one-piece zirconia abutment/crown (control) and a directly veneered
      fluorescent hybrid zirconia abutment/crown (test). Spectrophotometric assessment
      was performed: prior to abutment insertion (WA), at abutment try-in (A), at the
      try-in of the final crowns (C). Color differences (DeltaE) were assessed compared
      to the gingiva of natural teeth (T) and between the reconstructions. RESULTS: At
      abutment try-in, DeltaE values were 8.49 +/- 3.59 for AControl and 8.27 +/- 4.03
      for ATest compared to T. At crown insertion, DeltaE values were 7.61 +/- 4.03 for
      CControl and 8.32 +/- 3.57 for CTest compared to T. The difference in DeltaE
      values between AControl and ATest was 0.23 +/- 2.54 (P = .37), whereas the
      difference in DeltaE values between CControl and CTest was -0.66 +/-3.45 (P =
      .48). For all cases with a mucosal thickness <=2 mm, the comparison between
      CControl and CTest was significant in favor of the control group (P = .03).
      CONCLUSIONS: Both types of reconstructions were similar in terms of esthetics.
      Incases with a mucosal thickness of <2 mm, the soft tissue discoloration compared
      to the natural gingiva was more pronounced for the fluorescent hybrid zirconia
      reconstructions.

PMID- 28440008
TI  - Major bleeding risks of different low-molecular-weight heparin agents: a cohort
      study in 12 934 patients treated for acute venous thrombosis.
AB  - : Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may
      result in different bleeding risks. A cohort of 12 934 venous thrombosis patients
      on LMWH was followed until major bleeding. The absolute major bleeding risk was
      low among patients registered at the anticoagulation clinic. Once-daily dosing
      was associated with a lower bleeding risk as compared with twice-daily. SUMMARY:
      Background Low-molecular-weight heparins (LMWHs) are considered members of a
      class of drugs with similar anticoagulant properties. However, pharmacodynamics
      and pharmacokinetics between LMWHs differ, which may result in different bleeding
      risks. As these agents are used by many patients, small differences may lead to a
      large effect on numbers of major bleeding events. Objectives To determine major
      bleeding risks for different LMWH agents and dosing schedules. Methods A cohort
      of acute venous thrombosis patients from four anticoagulation clinics who used an
      LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or
      until major bleeding. Exposures were classified according to different types of
      LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per
      1000 patients and risk ratios were calculated and adjusted for study center.
      Results The study comprised 12 934 patients with a mean age of 59 years; 6218
      (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000
      patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was
      associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with
      nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated
      with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with
      a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were
      low for all LMWH agents and dosing schedules in a large unselected cohort.
      Nevertheless, twice-daily dosing with nadroparin appeared to be associated with
      an increased major bleeding risk as compared with once-daily dosing, as also
      suggested in a meta-analysis of controlled clinical trials.

PMID- 28440010
TI  - Self-concept mediates the relation between achievement and emotions in
      mathematics.
AB  - BACKGROUND: Mathematics achievement is related to positive and negative emotions.
      Pekrun's control-value theory of achievement emotions suggests that students'
      self-concept (i.e., self-appraisal of ability) may be an important mediator of
      the relation between mathematics achievement and emotions. AIMS: The aims were
      (1) to investigate the mediating role of mathematical self-concept in the
      relation between mathematics achievement and the achievement emotions of
      enjoyment and anxiety in a comprehensive model, and (2) to test possible
      differences in this mediating role between low-, average-, and high-achieving
      students. SAMPLE: Participants were ninth-grade students (n = 1,014) from eight
      secondary schools in the Netherlands. METHODS: Through an online survey including
      mathematical problems, students were asked to indicate their levels of
      mathematics enjoyment, anxiety, and self-concept. Structural equation modelling
      was used to test the mediating role of self-concept in the relation between
      mathematics achievement and emotions. Multigroup analyses were performed to
      compare these relations across the three achievement groups. RESULTS: Results
      confirmed full mediation of the relation between mathematics achievement and
      emotions by mathematical self-concept. Furthermore, we found higher self
      concepts, more enjoyment and less math anxiety in high-achieving students
      compared to their average and low-achieving peers. No differences across these
      achievement groups were found in the relations in the mediational model.
      CONCLUSIONS: Mathematical self-concept plays a pivotal role in students'
      appraisal of mathematics. Mathematics achievement is only one factor explaining
      students' self-concept. Likely also classroom instruction and teachers' feedback
      strategies help to shape students' self-concept.

PMID- 28440009
TI  - Sodium-glucose co-transporter 2 inhibitors for type 2 diabetes mellitus: An
      overview for the primary care physician.
AB  - AIMS: Sodium-glucose co-transporter type 2 (SGLT2) inhibitors are a new class of
      anti-hyperglycaemic agents in type 2 diabetes mellitus (T2DM). This review
      examines their mechanism of action and provides an overview of safety and
      efficacy from the main studies of SGLT2 inhibitors marketed in the United States
      and Europe, namely, canagliflozin, dapagliflozin and empagliflozin. METHODS: We
      searched the PubMed database to identify relevant publications on the mechanism
      of action of SGLT2 inhibitors and clinical trial reports. RESULTS: Clinical
      trials in patients with T2DM have shown significant improvements in glycaemic
      control vs placebo with canagliflozin, dapagliflozin and empagliflozin: patients
      were more likely to reach target glycated haemoglobin levels compared with
      patients receiving placebo. All SGLT2 inhibitors also led to modest reductions in
      body weight and blood pressure vs placebo. Generally, all agents were well
      tolerated, with the most common adverse events with this class being genital
      mycotic infections and urinary tract infections. Hypoglycaemia was reported at
      rates similar to those seen with placebo, except when SGLT2 inhibitors were given
      in combination with insulin or an insulin secretagogue. Long-term outcome data
      are available only for empagliflozin: in the EMPA-REG OUTCOME study,
      empagliflozin demonstrated reduced risk of the composite end-point of 3-point
      major adverse cardiovascular events (cardiovascular death, non-fatal myocardial
      infarction or non-fatal stroke), primarily because of a significant reduction in
      cardiovascular mortality. CONCLUSIONS: SGLT2 inhibitors are an exciting addition
      to the list of available agents for T2DM, and may be suitable for various types
      of patients who need additional glycaemic control.

PMID- 28440011
TI  - Intensity of factor VIII treatment and the development of inhibitors in non
      severe hemophilia A patients: results of the INSIGHT case-control study.
AB  - : Essentials Research suggests that intensive treatment episodes may increase the
      risk to develop inhibitors. We performed an international nested case-control
      study with 298 non-severe hemophilia A patients. Surgery and a high dose of
      factor VIII concentrate were associated with increased inhibitor risk. Physicians
      need to review arguments for factor VIII dose and elective surgery extra
      critically. SUMMARY: Background Inhibitor development is a major complication of
      treatment with factor VIII concentrates in hemophilia. Findings from studies
      among severe hemophilia A patients suggest that intensive treatment episodes
      increase the risk of developing inhibitors. Objectives We set out to assess
      whether intensive treatment is also associated with an increased risk of
      inhibitor development among non-severe hemophilia A patients. Patients/Methods We
      performed a nested case-control study. A total of 75 inhibitor patients (cases)
      and 223 control patients were selected from 2709 non-severe hemophilia A patients
      (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for
      date of birth and cumulative number of exposure days (EDs) to FVIII concentrates.
      Conditional logistic regression was used to calculate both unadjusted and
      adjusted odds ratios (aOR); the latter were adjusted for a priori specified
      confounders. Results Peak treatment of 5 or 10 consecutive EDs did not increase
      inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8;
      CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3)
      and a high mean dose (> 45 IU kg-1 /ED) of FVIII concentrate (aOR, 7.5; CI, 1.6
      35.6) were associated with an increased inhibitor risk. Conclusions Our findings
      suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor
      development in non-severe hemophilia A. Together with the notion that non-severe
      hemophilia A patients are at a lifelong risk of inhibitor development, we suggest
      that in the future physicians will review the arguments for the FVIII dose and
      elective surgery extra critically.

PMID- 28440012
TI  - Image-defined risk factors in unresectable neuroblastoma: SIOPEN study on
      incidence, chemotherapy-induced variation, and impact on surgical outcomes.
AB  - PURPOSE: To evaluate the impact of image-defined risk factor (IDRF) modification
      after chemotherapy on surgical outcomes, event-free survival (EFS), and overall
      survival (OS) among patients enrolled in the European Unresectable Neuroblastoma
      (EUNB) study. METHODS: IDRFs were assigned according to the corresponding
      surgical risk factors list reported in the database. Surgical outcomes, EFS, and
      OS were related to IDRF modification with chemotherapy. The predictive value of
      preoperative IDRF for surgical outcomes was analyzed. Cox proportional hazards
      models for EFS and OS, including preoperative IDRF, surgical outcomes, and other
      known clinical risk factors, were created. RESULTS: Of the 160 patients enrolled
      in the EUNB study, 143 patients met the inclusion criteria. A total of 228 IDRF
      were thus collected. Following chemotherapy, 76 (33%) IDRF disappeared in 32.2%
      of patients, 33 (14%) new IDRF appeared in 18.8% of patients, and 49% of patients
      did not show any IDRF change. Complete resection/minimal residual disease (71.2%)
      was more frequent among children who had disappearance/numerical reduction of
      IDRF (P = 0.005). Infiltration of the branches of the mesenteric artery was
      predictive of an unfavorable surgical outcome. Prolonged preoperative
      chemotherapy over five courses and encasement of the celiac axis and/or
      mesenteric artery origin impacted EFS and OS. CONCLUSIONS: The unchanged IDRF
      pattern in 50% of patients and the appearance of new IDRF during chemotherapy in
      approximately 20% of patients strengthens the idea that prolonged chemotherapy is
      useless for improving surgical resection in this population of patients. In
      addition, midline perivascular abdominal preoperative IDRF appeared to be
      predictive not only of surgical outcomes but also of EFS and OS.

PMID- 28440013
TI  - Sex-specific differences in the presenting location of a first venous
      thromboembolism.
AB  - : Essentials Whether the location of venous thromboembolism (VTE) differs between
      the sexes is not known. Pulmonary embolism as presenting location was relatively
      more common in women than in men. The difference was consistent among age groups
      and most prominent in unprovoked VTE. The underlying mechanism remains to be
      elucidated. SUMMARY: Background The risk of venous thromboembolism (VTE) differs
      between men and women. Some risk factors seem to influence the presenting
      location of VTE. Sex-specific differences in the presenting VTE location have not
      been studied extensively. Methods We analyzed data from the MEGA case-control
      study and the Hokusai-VTE study, and used published data from the RIETE registry.
      Data from patients with a symptomatic first VTE were included (MEGA, n = 4953;
      Hokusai-VTE, n = 6720; RIETE, n = 40 028). Distributions of deep vein thrombosis
      (DVT), pulmonary embolism (PE) and combined DVT and PE as the presenting VTE
      location were calculated for men and women, and presented as proportions with 95%
      confidence intervals (CIs). Sex-specific differences were explored for different
      age categories and for unprovoked and provoked events. Results In the MEGA study,
      PE was the presenting location in 35.5% of women and in 29.5% of men with VTE
      (difference 6.0%, 95% CI 3.4-8.6). In the Hokusai-VTE study, these proportions
      were 35.1% for women and 25.2% for men (difference 10.0%, 95% CI 7.8-12.2). In
      the RIETE registry, PE (with or without DVT) was also observed more often as the
      presenting location in women (53.3%) than in men (47.7%), with a difference of
      5.6% (95% CI 4.7-6.6). The observed higher proportion of PE as the presenting
      location in women was present in all age groups and was most prominent among
      unprovoked VTE events. Conclusions In three large studies, the distribution of
      the presenting VTE location differed consistently between the sexes, whereby PE
      was more often the primary location of presentation in women than in men.

PMID- 28440014
TI  - Biomass Derived N-Doped Porous Carbon Supported Single Fe Atoms as Superior
      Electrocatalysts for Oxygen Reduction.
AB  - Exploring sustainable and high-performance electrocatalysts for the oxygen
      reduction reaction (ORR) is the crucial issue for the large-scale application of
      fuel cell technology. A new strategy is demonstrated to utilize the biomass
      resource for the synthesis of N-doped hierarchically porous carbon supported
      single-atomic Fe (SA-Fe/NHPC) electrocatalyst toward the ORR. Based on the
      confinement effect of porous carbon and high-coordination natural iron source, SA
      Fe/NHPC, derived from the hemin-adsorbed bio-porphyra-carbon by rapid heat
      treatment up to 800  degrees C, presents the atomic dispersion of Fe atoms in the
      N-doped porous carbon. Compared with the molecular hemin and nanoparticle Fe
      samples, the as-prepared SA-Fe/NHPC exhibits a superior catalytic activity (E1/2
      = 0.87 V and Jk = 4.1 mA cm-2 , at 0.88 V), remarkable catalytic stability (~1 mV
      negative shift of E1/2 , after 3000 potential cycles), and outstanding methanol
      tolerance, even much better than the state-of-the-art Pt/C catalyst. The
      sustainable and effective strategy for utilizing biomass to achieve high
      performance single-atom catalysts can also provide an opportunity for other
      catalytic applications in the atomic scale.

PMID- 28440015
TI  - Hypertriglyceridemia during asparaginase treatment in children with acute
      lymphoblastic leukemia correlates with antithrombin activity in adolescents.
AB  - BACKGROUND: Asparaginase (ASP) is a cornerstone in the treatment of acute
      lymphoblastic leukemia (ALL). It is also known for its ability to cause side
      effects, such as allergy and pancreatitis, as well as lipid and coagulation
      disturbances. The most important laboratory abnormalities are
      hypertriglyceridemia (HTG) and low antithrombin (AT). HTG is usually considered
      to be transient and benign in children with ALL, whereas low AT activity
      predisposes to thrombosis. Studies on the incidence and significance of HTG in
      children with ALL are scarce, and their findings have not always been congruent.
      We investigated the incidence and significance of ASP-related HTG, defined as
      triglyceride values more than five times the upper normal limit, in children with
      ALL. PROCEDURE: We analyzed the laboratory and clinical data of children
      diagnosed with ALL at the Karolinska Hospital, Stockholm, Sweden, from July 2008
      to December 2014. Triglyceride and AT values were measured before each injection
      of pegylated ASP. RESULTS: The study group comprised of 92 patients, aged 1-17.9
      years at diagnosis (median 4.8 years), almost half (42/92, 46%) of whom had HTG.
      A significant negative correlation between triglyceride and AT values was
      observed in those aged over 10 years (P = 0.0002). No significant correlation was
      found between HTG and thrombosis, osteonecrosis, or pancreatitis. CONCLUSIONS:
      Although common, ASP-associated HTG was not associated with other ASP-related
      toxicities. HTG correlated with decreased AT activity in older children, which
      may explain previous association between HTG and thrombosis. Larger studies are
      of interest with regard to establishing guidelines for HGT management.

PMID- 28440016
TI  - Outcomes and feasibility of the short transitional intervention in psychiatry in
      improving the transition from inpatient treatment to the community: A pilot
      study.
AB  - Discharge from psychiatric inpatient care is frequently described as chaotic,
      stressful, and emotionally charged. Following discharge, service users are
      vulnerable to becoming overwhelmed by the challenges involved in readapting to
      their home environments, which could result in serious problems and lead to
      readmission. The short transitional intervention in psychiatry (STeP) is a
      bridging intervention that includes pre- and post-discharge sections. It aims to
      prepare patients for specific situations in the period immediately following
      discharge from a psychiatric hospital. We conducted a quasi-experimental pilot
      study to determine the feasibility of the intervention, and gain insight into the
      effects of the STeP. Two inpatient wards at a Swiss psychiatric hospital
      participated in the study, and represented the intervention and control arms.
      Patient recruitment and baseline assessment were performed 2 weeks prior to
      discharge. Follow-up data were collected 1 week subsequent to discharge.
      Questionnaires measured coping, admission and health-care usage, self-efficacy,
      working alliance, experience of transition, and the number of difficulties
      experienced following discharge. Fourteen and 15 patients completed the follow-up
      assessment in the control and intervention groups, respectively. The STeP did not
      affect primary or secondary outcomes; however, it was shown to be feasible, and
      patients' feedback highlighted the importance of post-discharge contact sessions.
      Further research is required to improve understanding of the discharge
      experience, identify relevant patient outcomes, and assess the effectiveness of
      the intervention in an adequately-powered randomized, controlled trial.

PMID- 28440017
TI  - A study of the VaSera arterial stiffness device in US patients.
AB  - The cardio-ankle vascular index (CAVI) represents a promising index of arterial
      stiffness. However, neither the CAVI measure nor its measurement device, the
      VaSera, have undergone general testing in a North American clinical setting. To
      begin the process of collecting normal values in the United States, we studied 20
      male and 28 female volunteers without reported cardiovascular or renal disease
      and no history of smoking. Their CAVIs, ankle-brachial indices (ABIs), and four
      limb blood pressures were measured in three positions: supine, 7 degrees 
      Trendelenburg, and 7 degrees  reverse Trendelenburg. In addition, the ABI
      function was validated against an established ABI measurement technique. Position
      was found to affect CAVI and other hemodynamic parameters, indicating that CAVI
      is not robust to slight positional variations. No differences were found in the
      blood pressure between arms or legs (interbrachial or interankle), supporting
      recent findings from meta-analyses and studies but contradicting other work. This
      study represents an early step in bringing the VaSera device and its CAVI
      measurement into clinical practice.

PMID- 28440018
TI  - Clear cell sarcoma of kidney involving a horseshoe kidney and harboring EGFR
      internal tandem duplication.
AB  - Clear cell sarcoma of kidney (CCSK) is a rare renal malignancy, previously
      unreported in horseshoe kidney (HSK). B-cell lymphoma 6 corepressor (BCOR) gene
      internal tandem duplication (ITD) was identified as a recurrent somatic
      alteration in approximately 85% of CCSKs. This and the YWHAE-NUTM2B/E fusion, the
      second most common recurrent molecular alteration in CCSK (10%), are considered
      to be mutually exclusive. However, there is a subset of CCSKs that do not harbor
      either the BCOR-ITD or YWHAE-NUTM2 translocation and lack known molecular
      alterations. Herein, we report the first case of CCSK arising in HSK and
      harboring epidermal growth factor receptor ITD.

PMID- 28440019
TI  - Cervical cancer risk and impact of Pap-based screening in HIV-positive women on
      antiretroviral therapy in Johannesburg, South Africa.
AB  - Data on invasive cervical cancer (ICC) incidence in HIV-positive women and the
      effect of cervical cancer screening in sub-Saharan Africa are scarce. We
      estimated i) ICC incidence rates in women (>=18 years) who initiated
      antiretroviral therapy (ART) at the Themba Lethu Clinic (TLC) in Johannesburg,
      South Africa, between 2004 and 2011 and ii) the effect of a Pap-based screening
      program. We included 10,640 women; median age at ART initiation: 35 years
      [interquartile range (IQR) 30-42], median CD4 count at ART initiation: 113
      cells/uL (IQR 46-184). During 27,257 person-years (pys), 138 women were diagnosed
      with ICC; overall incidence rate: 506/100,000 pys [95% confidence interval (CI)
      428-598]. The ICC incidence rate was highest (615/100,000 pys) in women who
      initiated ART before cervical cancer screening became available in 04/2005 and
      was lowest (260/100,000 pys) in women who initiated ART from 01/2009 onward when
      the cervical cancer screening program and access to treatment of cervical lesions
      was expanded [adjusted hazard ratio (aHR) 0.42, 95% CI 0.20-0.87]. Advanced
      HIV/AIDS stage (4 versus 1, aHR 1.95, 95% CI 1.17-3.24) and middle age at ART
      initiation (36-45 versus 18-25 years, aHR 2.51, 95% CI 1.07-5.88) were risk
      factors for ICC. The ICC incidence rate substantially decreased with the
      implementation of a Pap-based screening program and improved access to treatment
      of cervical lesions. However, the risk of developing ICC after ART initiation
      remained high. To inform and improve ICC prevention and care for HIV-positive
      women in sub-Saharan Africa, implementation and monitoring of cervical cancer
      screening programs are essential.

PMID- 28440020
TI  - Interconnected 3 D Network of Graphene-Oxide Nanosheets Decorated with Carbon
      Dots for High-Performance Supercapacitors.
AB  - Interconnected 3 D nanosheet networks of reduced graphene oxide decorated with
      carbon dots (rGO/CDs) are successfully fabricated through a simple one-pot
      hydrothermal process. The as-prepared rGO/CDs present appropriate 3 D
      interconnectivity and abundant stable oxygen-containing functional groups, to
      which we can attribute the excellent electrochemical performance such as high
      specific capacitance, good rate capability, and great cycling stability. Employed
      as binder-free electrodes for supercapacitors, the resulting rGO/CDs exhibit
      excellent long-term cycling stability (ca. 92 % capacitance retention after 20
      000 charge/discharge cycles at current density of 10 A g-1 ) as well as a maximum
      specific capacitance of about 308 F g-1 at current density of 0.5 A g-1 , which
      is much higher than that of rGO (200 F g-1 ) and CDs (2.2 F g-1 ). This work
      provides a promising strategy to fabricate graphene-based nanomaterials with
      greatly boosted electrochemical performances by decoration of with CDs.

PMID- 28440021
TI  - Global patterns and trends in human-wildlife conflict compensation.
AB  - Human-wildlife conflict is a major conservation challenge, and compensation for
      wildlife damage is a widely used economic tool to mitigate this conflict. The
      effectiveness of this management tool is widely debated. The relative importance
      of factors associated with compensation success is unclear, and little is known
      about global geographic or taxonomic differences in the application of
      compensation programs. We reviewed research on wildlife-damage compensation to
      determine geographic and taxonomic gaps, analyze patterns of positive and
      negative comments related to compensation, and assess the relative magnitude of
      global compensation payments. We analyzed 288 publications referencing wildlife
      compensation and identified 138 unique compensation programs. These publications
      reported US$222 million (adjusted for inflation) spent on compensation in 50
      countries since 1980. Europeans published the most articles, and compensation
      funding was highest in Europe, where depredation by wolves and bears was the most
      frequently compensated damage. Authors of the publications we reviewed made twice
      as many negative comments as positive comments about compensation. Three-quarters
      of the negative comments related to program administration. Conversely, three
      quarters of the positive comments related to program outcomes. The 3 most common
      suggestions to improve compensation programs included requiring claimants to
      employ damage-prevention practices, such as improving livestock husbandry or
      fencing of crops to receive compensation (n = 25, 15%); modifying ex post
      compensation schemes to some form of outcome-based performance payment (n = 21,
      12%); and altering programs to make compensation payments more quickly (n = 14,
      8%). We suggest that further understanding of the strengths and weaknesses of
      compensation as a conflict-mitigation tool will require more systematic
      evaluation of the factors driving these opinions and that differentiating process
      and outcomes and understanding linkages between them will result in more fruitful
      analyses and ultimately more effective conflict mitigation.

PMID- 28440022
TI  - MiR-372-3p promotes cell growth and metastasis by targeting FGF9 in lung squamous
      cell carcinoma.
AB  - The aim of this study was to study the role of miR-372-3p in lung squamous cell
      carcinoma (LSCC) cell proliferation and invasion by suppressing FGF9. RT-PCR was
      used to determine miR-372-3p and FGF9 mRNA expression in tissues and cells.
      Western blot was used to determine FGF9 expression in tissues and NCI-H520 cell
      line. Dual luciferase reporter gene assay was conducted to confirm that FGF9 can
      be directly targeted by miR-372-3p. MTT, colony formation assays were conducted
      to investigate the effects of ectopic miR-372-3p and FGF9 expression on NCI-H520
      cell growth. Flow cytometry was used to analyze the influence of miR-372-3p and
      FGF9 expression on cell cycle distribution and apoptosis. Transwell assay was
      also conducted to see the effects of miR-372-3p and FGF9 expression on NCI-H520
      cell invasiveness. MiR-372-3p was found significantly overexpressed in both LSCC
      tissues and cell lines, whereas FGF9 mRNA was found underexpressed in LSCC
      tissues. MiR-372-3p directly bound to wild-type FGF9 mRNA 3'UTR, therefore led to
      the reduction in FGF9 expression. The upregulation of FGF9 or the downregulation
      of miR-372-3p substantially retarded LSCC cell growth, mitosis, and invasion. MiR
      372-3p enhanced LSCC cell proliferation and invasion through inhibiting FGF9.

PMID- 28440023
TI  - Cytomorphologic features of echinococcal cysts.

PMID- 28440024
TI  - Immediate and delayed loading of two-piece reduced-diameter implants with locator
      analog attachments in edentulous mandibles: One-year results from a randomized
      clinical trial examining clinical outcome and patient expectation.
AB  - BACKGROUND: Prosthetic management of thin alveolar ridges in the edentulous
      mandibles of elderly patients, especially the time of loading, the number of
      implants needed, and patient expectations and perception, is a challenge in
      implant dentistry. PURPOSE: Survival of conventionally and immediately loaded 2
      piece reduced-diameter implants in the interforaminal region of the edentulous
      mandible supporting locator-analog attachments was evaluated. Prosthetic
      complications and peri-implant hygiene were also studied, and patient expectation
      and subjective evaluation of the treatment were documented. MATERIAL AND METHODS:
      Twenty-five patients with adapted complete dentures received 4 reduced-diameter
      implants. All anterior implants were immediately loaded. Three months later,
      patients were allocated by randomization to 1 of 2 treatment groups: 2 locator
      analog attachments on the anterior implants (Group A); or 4 locator-analog
      attachments (Group B). After another 3 months patient allocation was changed
      (crossover design) for the next 3 months. Questionnaires with Likert scales and
      numeric rating scales were used to assess patients' expectations and subjective
      overdenture-related variables, respectively. RESULTS: One implant was lost in the
      immediate-loading group. Survival was 98% and 100% for immediate and delayed
      loading, respectively. During 12-month observation, 8 complications required
      aftercare. At the beginning of treatment, patients' expectations were highly
      positive. Subjective assessment of overdenture-related variables 3 months after
      immediate loading of 2 implants revealed a statistically significant improvement
      for most of the variables studied; this was maintained 1 year later. In the
      subjective assessments, there were no statistically significant differences
      between Groups A and B. CONCLUSION: Immediate loading of reduced-diameter
      implants supporting locator-analog attachments resulted in high implant survival,
      few prosthetic complications, good oral hygiene, and improvement of subjective
      denture perception in the short-term. It might be a promising treatment option,
      especially for elderly patients with a narrow mandibular ridge.

PMID- 28440025
TI  - Identifying key genes in rheumatoid arthritis by weighted gene co-expression
      network analysis.
AB  - PURPOSE: This study aimed to identify rheumatoid arthritis (RA) related genes
      based on microarray data using the WGCNA (weighted gene co-expression network
      analysis) method. METHODS: Two gene expression profile datasets GSE55235 (10 RA
      samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy
      controls) were downloaded from Gene Expression Omnibus database. Characteristic
      genes were identified using metaDE package. WGCNA was used to find disease
      related networks based on gene expression correlation coefficients, and module
      significance was defined as the average gene significance of all genes used to
      assess the correlation between the module and RA status. Genes in the disease
      related gene co-expression network were subject to functional annotation and
      pathway enrichment analysis using Database for Annotation Visualization and
      Integrated Discovery. Characteristic genes were also mapped to the Connectivity
      Map to screen small molecules. RESULTS: A total of 599 characteristic genes were
      identified. For each dataset, characteristic genes in the green, red and
      turquoise modules were most closely associated with RA, with gene numbers of 54,
      43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene
      Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1,
      etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and
      homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs
      sanguinarine and papaverine were predicted to have a therapeutic effect against
      RA. CONCLUSION: Genes related to immune response, inflammatory response and
      homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and
      papaverine have a potential therapeutic effect against RA.

PMID- 28440026
TI  - miR-148b inhibits glycolysis in gastric cancer through targeting SLC2A1.
AB  - Although the molecular biology of GC has been well characterized, early
      diagnostic biomarkers and effective therapeutic options in gastric cancer are
      still under investigation. Here, we found that miR-148b expression decreased in
      human gastric cancer tissues compared with matched adjacent nontumor tissues by q
      PCR analysis and in situ hybridization. Further investigation revealed that
      overexpression of miR-148b limited glycolysis including glucose consumption,
      lactate production in gastric cancer cell lines BGC-823 and MKN45. Bioinformatics
      prediction uncovered that a dedicated transporters solute carrier family 2 member
      1 (SLC2A1), also called GLUT1, was the direct target of miR-148b. The target
      effects were further confirmed by luciferase assay and western blot analysis.
      Besides, a reverse correlation was observed between relative SLC2A1 and miR-148b
      expression in human GC tissues compared with matched adjacent nontumor tissues.
      Subsequently, SLC2A1 suppression by SLC2A1 siRNA or specific inhibitor restricted
      the reduced effects of glycolysis mediated by miR-148b while SLC2A1
      overexpression abrogated the effect of miR-148b on glycolysis. Our findings
      provided new evidence of miR-148b in GC development through restraining
      glycolysis, highlighting the role of miR-148b as a new target for GC treatment.

PMID- 28440027
TI  - The CRISPR/Cas9 system: Their delivery, in vivo and ex vivo applications and
      clinical development by startups.
AB  - The CRISPR/Cas9 gene editing system was originally derived from the prokaryotic
      adaptive immune system mediated by Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR) and CRISPR-associated proteins (Cas). The system has
      been successfully applied to genome editing in eukaryotes and has contributed to
      remarkable advances in the life sciences, in areas ranging from agriculture to
      genetic disease therapies. For efficient editing and extending the influence of
      this system, proper delivery of its components is crucial. Both viral and
      nonviral delivery methods are reviewed here, along with the advantages and
      disadvantages of each. In addition, we review ex vivo and in vivo CRISPR/Cas9
      applications for disease therapies. Related remarkable studies are highlighted
      and relevant startup companies and their drug development pipelines are
      described. (c) 2017 American Institute of Chemical Engineers Biotechnol. Prog.,
      33:1035-1045, 2017.

PMID- 28440028
TI  - Rhodium(III)-Catalyzed Annulative Carbooxygenation of 1,1-Disubstituted Alkenes
      Triggered by C-H Activation.
AB  - A Cp*RhIII -catalyzed annulative carbooxygenation of challenging 1,1
      disubstituted alkenes triggered by C-H activation of N-aryloxyacetamides has been
      established, which affords 2,3-dihydrobenzofuran derivatives with a quaternary
      carbon center in good to excellent yields under mild redox-neutral conditions. An
      amide group on the alkenes is essential for the process, and may inhibit the beta
      H elimination from C(sp3)-Rh species by saturating the rhodium center through
      coordination. Furthermore, mechanistic insights obtained from control experiments
      suggest a mechanism involving a RhIII -RhV -RhIII catalytic cycle.

PMID- 28440029
TI  - Treatment effects of Reverse Twin-Block and Reverse Pull Face Mask on
      craniofacial morphology in early and late mixed dentition children.
AB  - OBJECTIVE: Reverse Twin-Block (RTB) and Reverse Pull Face Mask (RPFM) appliances
      are used to correct Class III malocclusion in growing patients. Aim of this
      retrospective study was to compare and analyse craniofacial changes produced by
      RTB and RPFM in the early and late mixed dentition in Malay children with Class
      III malocclusion. METHODS: Data consisted of pre- and post-treatment lateral
      cephalograms of 95 children, 49 patients with RTB and 46 patients with RPFM,
      divided into an early (8-9 year) and late (10-11 year) group. Treatment changes
      were assessed by the Ricketts analysis using CASSOS software, where 71 anatomic
      landmarks were identified in each cephalogram. Paired and independent t tests
      were performed for statistical comparison. RESULTS: Paired t test revealed
      significant changes in facial axis, facial angle, MD plane to FH, lower facial
      height, mandibular arc, maxillary convexity, U1 to APog, L1 to APog, L1 to APog
      angle and upper lip to E-plane measurements in RPFM, whereas significant changes
      were found in facial taper, U1 to APog and lower lip to E-plane values with RTB
      in the early treatment group. Independent t test revealed significant changes in
      U1 to APog, L1 to APog and U6 to PtV values in the RTB group. Post-treatment
      comparison of RTB and RPFM showed significant differences in L1 to APog and L1 to
      APog angle values. CONCLUSIONS: RPFM revealed more favourable craniofacial
      changes than RTB, particularly in the late mixed dentition stage.

PMID- 28440030
TI  - Identification of target genes downstream of semaphorin6A/PlexinA2 signaling in
      zebrafish.
AB  - BACKGROUND: Semaphorin (Sema)/Plexin (Plxn) signaling is important for many
      aspects of neuronal development, however, the transcriptional regulation imposed
      by this signaling pathway is unknown. Previously, we identified an essential role
      for Sema6A/PlxnA2 signaling in regulating proliferation and cohesion of retinal
      precursor cells (RPCs) during early eye development. This study used RNA isolated
      from control, Sema6A-deficient and PlxnA2-deficient zebrafish embryos in a
      microarray analysis to identify genes that were differentially expressed when
      this signaling pathway was disrupted. RESULTS: We uncovered a set of 58
      transcripts, and all but 1 were up-regulated in both sema6A and plxnA2 morphants.
      We validated gene expression changes in subset of candidates that are suggested
      to be involved in proliferation, migration or neuronal positioning. We further
      functionally evaluated one gene, rasl11b, as contributing to disrupted
      proliferation in sema6A and plxna2 morphants. Our results suggest rasl11b
      negatively regulates proliferation of RPCs in the developing zebrafish eye.
      CONCLUSIONS: Microarray analysis has generated a resource of target genes
      downstream of Sema6A/PlxnA2 signaling, which can be further investigated to
      elucidate the downstream effects of this well-studied neuronal and vascular
      guidance signaling pathway. Developmental Dynamics 246:539-549, 2017. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28440031
TI  - Production, characterization, and assessment of a stable analog of the response
      regulator CheY-phosphate from Thermotoga maritima.
AB  - Phosphorylation of CheY promotes association with the flagellar motor and
      ultimately controls the directional bias of the motor. However, biochemical
      studies of activated CheY-phosphate have been challenging due to the rapid
      hydrolysis of the aspartyl-phosphate in vitro. An inert analog of Tm CheY
      phosphate, phosphono-CheY, was synthesized by chemical modification and purified
      by cation-exchange chromatography. Changes in HPLC retention times, chemical
      assays for phosphate and free thiol, and mass spectrometry experiments
      demonstrate modification of Cys54 with a phosphonomethyl group. Additionally, a
      crystal structure showed electron density for the phosphonomethyl group at Cys54,
      consistent with a modification at that position. Subsequent biochemical
      experiments confirmed that protein crystals were phosphono-CheY. Isothermal
      titration calorimetry and fluorescence polarization binding assays demonstrated
      that phosphono-CheY bound a peptide derived from FliM, a native partner of CheY
      phosphate, with a dissociation constant of ~29 uM, at least sixfold more tightly
      than unmodified CheY. Taken together these results suggest that Tm phosphono-CheY
      is a useful and unique analog of Tm CheY-phosphate.

PMID- 28440032
TI  - Discrepancies between the one-stage clotting assay and the chromogenic assay in
      haemophilia B.
AB  - INTRODUCTION: Assay discrepancy in factor VIII activity between the one-stage and
      the chromogenic assays has been described in approximately one third of patients
      with non-severe haemophilia A. Whether assay discrepancy may also occur in
      patients with haemophilia B remains unknown. AIM: This study compared the results
      from the one-stage and the chromogenic assays in patients with haemophilia B.
      METHODS: Plasma samples from patients with haemophilia B attending the
      haemophilia centre in Malmo, Sweden, were collected after a wash-out period of
      more than 7 days and analysed with both assays. RESULTS: Fifty samples from 36
      patients were analysed. No discrepancy was found in patients with severe
      haemophilia B. Among the 44 plasma samples from patients with non-severe disease,
      15 showed a twofold or greater difference between the results of the two methods,
      with the chromogenic method presenting the higher value (mean FIX:Cone-stage 0.02
      vs. FIX:Cchromo 0.06 IU mL-1 ). Of these 15 samples, 14 were from seven
      individuals from five families with the same mutated amino acid at the N-terminal
      cleaving site of the activation peptide (FIX: c.572G>A; p.Arg191His or FIX:
      c.571C>T; p.Arg191Cys). These mutations were not observed in any patients with
      non-discrepant results. The reported bleeding frequency for these patients was
      low and indicative of a mild bleeding phenotype. CONCLUSION: Our findings imply
      that assay discrepancy occurs for factor IX activity and that both type of assays
      are needed for a correct diagnosis and classification of haemophilia B. The
      underlying mechanism by which the mutation influences the assays remains to be
      determined.

PMID- 28440033
TI  - Rigor, reproducibility, and in vitro cerebrospinal fluid assays: The devil in the
      details.

PMID- 28440034
TI  - Role of transcranial direct current stimulation on reduction of postsurgical
      opioid consumption and pain in total knee arthroplasty: Double randomized
      clinical trial.
AB  - BACKGROUND: Postoperative pain control is an important factor in determining
      recovery in total knee arthroplasty (TKA).The aim of the study was to assess the
      efficacy of 4 sessions of transcranial direct current stimulation (tDCS) over
      primary motor cortex (M1) in patients undergoing unilateral TKA. MATERIALS: Fifty
      patients undergoing TKA were included in the study. They were divided randomly
      into two groups (25 patients for each, using closed envelopes): real tDCS (2 mA,
      20 min, with anodal stimulation applied over M1 postoperative for 4 consecutive
      days) and sham tDCS. Opioid consumption was titrated by an anaesthesiologist
      during the study period and was used as primary outcome. As a secondary outcome,
      patients were evaluated using Visual Analogue Scale (VAS) and Leeds Assessment of
      Neuropathic Symptoms and Signs Pain Scale (LANSS) at baseline, then the 1st, 2nd,
      3rd and 4th days after operation. RESULTS: There was no significant difference
      between real and sham tDCS in any rating scales at baseline. The opioid
      consumption and LANSS scores decreased more in patients who received real tDCS
      over the course of the treatment than sham tDCS. Real tDCS was associated with
      59% reduction in the titrated analgesia. There was no significant difference
      between groups (time * groups interaction) in the VAS. CONCLUSION: Since the VAS
      was constant, repeated sessions of anodal tDCS over M1 with an extra-cephalic
      cathodal electrode can achieve the same degree of analgesia with less opioid
      consumption over the postoperative days after TKA. Thus, tDCS is a promising tool
      in the field of postoperative analgesia. SIGNIFICANCE: The data of the present
      study suggest that four sessions of transcranial direct current brain stimulation
      over motor cortex could reduce morphine consumption and pain perception during
      the postoperative period in total knee arthroplasty.

PMID- 28440035
TI  - MiR-145 inhibits human colorectal cancer cell migration and invasion via PAK4
      dependent pathway.
AB  - MicroRNA-145 (miR-145), as a tumor-suppressive miRNA, has been demonstrated down
      regulated in colorectal cancer (CRC) cells, and could inhibit CRC cells growth.
      However, the molecular pathway in which miR-145 modulates CRC malignant
      transformation has not been fully revealed. Here, we reported an intense
      correlation between the expressions of PAK4 and miR-145 in human CRC cell lines.
      Transwell assay verified overexpression of miR-145, as well as knockdown of PAK4,
      significantly suppressed cell migration and invasion ability. The impaired
      migration and invasion ability of SW1116 cells was affected through the down
      regulation of phosphorylation level of LIMK1 and cofilin in a PAK4-dependent
      manner. Collectively, we have demonstrated that miR-145 suppressed CRC migration
      and invasion through PAK4 pathway, which provides an attractive microRNA-based
      therapeutic target for CRC.

PMID- 28440037
TI  - Welcome Brad Bundy and Caryn Heldt.

PMID- 28440038
TI  - Induced Chemical Defense of a Mushroom by a Double-Bond-Shifting Polyene
      Synthase.
AB  - The antilarval mushroom polyenes 18-methyl-19-oxoicosaoctaenoic acid and 20
      methyl-21-oxodocosanonaenoic acid appear in response to injury of the mycelium of
      the stereaceous mushroom BY1. We identified a polyketide synthase (PPS1) which
      belongs to a hitherto completely uncharacterized clade of polyketide synthases.
      Expression of the PPS1 gene is massively upregulated following mycelial damage.
      The synthesis of the above polyenes was reconstituted in the mold Aspergillus
      niger as a heterologous host. This demonstrates that PPS1 1) synchronously
      produces branched-chain polyketides of varied lengths, and 2) catalyzes the
      unprecedented shift of eight or nine double bonds. This study represents the
      first characterization of a reducing polyketide synthase from a mushroom. We also
      show that injury-induced de novo synthesis of polyketides is a fungal response
      strategy.

PMID- 28440039
TI  - Effect of photoactivation on the reduction of composite resin contamination.
AB  - Composite resins are predominantly marketed in developing countries in tube form,
      and the contents of the tube may be used in numerous procedures for different
      patients. This represents a problem because of the risk of cross-contamination.
      This study aimed to evaluate contamination in vitro of the internal contents of
      composite resin tubes in the dental clinics of a higher-education institution, as
      well as the effect of photoactivation on the level of contamination. Twenty-five
      tubes containing composite resin were randomly chosen (by lottery). From each
      tube, two samples of approximately 2 mm of composite resin were removed, and then
      one sample, but not the other, was photoactivated. These samples were plated on
      Brain-Heart Infusion (BHI), Sabouraud and MacConkey agars, and the plates were
      incubated at 37 degrees C for 24-48 h. Colony counting and Gram staining were
      performed for subsequent microscopic identification of fungi and bacteria. The
      non-photoactivated composite resin group presented significantly higher microbial
      contamination in relation to the photoactivated composite resin group. The
      photoactivation of camphorquinone present in composite resin produces reactive
      oxygen species, which might promote cell death of contaminant microorganisms.
      Thus, although the same tube of composite resin may be used for a number of
      different patients in the dental clinics of developing countries, the
      photoactivation process potentially reduces the risk of cross-contamination.

PMID- 28440040
TI  - Hypofractionated short-course radiotherapy in elderly patients with glioblastoma
      multiforme: an analysis of the National Cancer Database.
AB  - For elderly patients with glioblastoma multiforme (GBM), randomized trials have
      shown similar survival with hypofractionated short-course radiotherapy (SCRT)
      compared to conventionally fractionated long-course radiotherapy (LCRT). We
      evaluated the adoption of SCRT along with associated factors and survival in a
      national patient registry. Using the National Cancer Data Base (NCDB), we
      identified patients aged >=70 years with GBM, diagnosed between 1998 and 2011,
      who received SCRT (34-42 Gy in 2.5-3.4 Gy fractions), or LCRT (58-63 Gy in 1.8
      2.0 Gy fractions). Crude and adjusted hazard ratios (HR) were calculated using
      Cox regression modeling. 4598 patients were identified, 304 (6.6%) in the SCRT
      group and 4294 (93.4%) in the LCRT group. Median follow-up was 8.4 months. Median
      age was 78 versus 75 years, respectively (P < 0.0001). Patients who received SCRT
      had higher Charlson-Deyo comorbidity scores versus LCRT (score of >=2: 16.9% vs.
      10.8%, respectively; P = 0.006), and were more likely to be female (53.0% vs.
      44.6%, P = 0.005). Patients who received SCRT were less likely to undergo
      chemotherapy (42.8% vs. 79.3%, P < 0.0001), more likely to undergo biopsy only
      (34.5% vs. 19.5%, P < 0.0001), and more likely to receive treatment at
      academic/research programs (49.2% vs. 37.2%, P = 0.0001). Median survival was 4.9
      months versus 8.9 months, respectively (P < 0.0001). The survival detriment with
      SCRT persisted on multivariable analysis [HR 1.51 (95% CI: 1.33-1.73, P <
      0.0001)], adjusting for age, gender, race, comorbidities, diagnosis year,
      facility type, surgery, and chemotherapy. In conclusion, hypofractionated SCRT
      was associated with worse survival compared to conventionally fractionated LCRT
      for elderly patients with GBM. Patients who received SCRT were older with worse
      comorbidities, and were less likely to undergo chemotherapy or resection.

PMID- 28440036
TI  - A tale of two countries: all-cause mortality among people living with HIV and
      receiving combination antiretroviral therapy in the UK and Canada.
AB  - OBJECTIVES: We sought to compare all-cause mortality of people living with HIV
      and accessing care in Canada and the UK. METHODS: Individuals from the Canadian
      Observational Cohort (CANOC) collaboration and UK Collaborative HIV Cohort (UK
      CHIC) study who were aged >= 18 years, had initiated antiretroviral therapy (ART)
      for the first time between 2000 and 2012 and who had acquired HIV through sexual
      transmission were included in the analysis. Cox regression was used to
      investigate the difference in mortality risk between the two cohort
      collaborations, accounting for loss to follow-up as a competing risk. RESULTS: A
      total of 19 960 participants were included in the analysis (CANOC, 4137; UK CHIC,
      15 823). CANOC participants were more likely to be older [median age 39 years
      (interquartile range (IQR): 33, 46 years) vs. 36 years (IQR: 31, 43 years) for UK
      CHIC participants], to be male (86 vs. 73%, respectively), and to report men who
      have sex with men (MSM) sexual transmission risk (72 vs. 56%, respectively) (all
      P < 0.001). Overall, 762 deaths occurred during 98 798 person-years (PY) of
      follow-up, giving a crude mortality rate of 7.7 per 1000 PY [95% confidence
      interval (CI): 7.1, 8.3 per 1000 PY]. The crude mortality rates were 8.6 (95% CI:
      7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study
      participants, respectively. No statistically significant difference in mortality
      risk was observed between the cohort collaborations in Cox regression accounting
      for loss to follow-up as a competing risk (adjusted hazard ratio 0.86; 95% CI:
      0.72-1.03). CONCLUSIONS: Despite differences in national HIV care provision and
      treatment guidelines, mortality risk did not differ between CANOC and UK CHIC
      study participants who acquired HIV through sexual transmission.

PMID- 28440041
TI  - Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute
      iliofemoral deep vein thrombosis: 1-year follow-up data of a randomized
      controlled trial.
AB  - : Essentials Acute iliofemoral deep vein thrombosis can be treated with catheter
      directed thrombolysis (CDT). We performed a randomized trial comparing
      conventional CDT versus ultrasound-assisted CDT (USAT). Clinical and duplex
      sonographic outcomes at 12 months were similar in the CDT and USAT groups. In
      both groups, incidence of postthrombotic syndrome was very low with good quality
      of life. SUMMARY: Background In patients with acute iliofemoral deep vein
      thrombosis (IFDVT), catheter-directed thrombolysis (CDT) aims to prevent the
      postthrombotic syndrome (PTS). Adding intravascular high-frequency, low-power
      ultrasound energy to CDT does not seem to improve the immediate thrombolysis
      results but its impact on clinical outcomes at 12 months is not known.
      Patients/Methods In this randomized-controlled trial, 48 patients (mean age 50 +/
      21 years; 52% women) with acute IFDVT were randomized to conventional CDT (n =
      24) or ultrasound-assisted CDT (USAT; n = 24). In both groups, a fixed-dose
      thrombolysis regimen (20 mg r-tPA over 15 h) was used, followed by routine
      stenting of residual venous obstruction. At 12 months, PTS and venous disease
      severity (Villalta score and revised Venous Clinical Severity Score [rVCSS]),
      disease-specific quality of live (QOL; CIVIQ-20) and duplex-sonographic outcomes
      were assessed. Results Among the 45 surviving patients, 40 (89%; 95% confidence
      interval [CI] 76-96%) patients were free from PTS (defined as Villalta score < 5
      points; 83%, 95% CI 61-95% in the USAT and 96%, 95% CI 77-100% in the CDT group),
      with a similar mean total Villalta score of 2.3 +/- 2.9 vs. 1.7 +/- 1.6, and a
      mean total rVCSS of 3.0 +/- 3.5 vs. 2.7 +/- 2.9 in the USAT and the CDT groups,
      respectively. Both groups had good disease-specific QOL with a CIVIQ-20 score of
      29.4 +/- 11.8 vs. 26.1 +/- 7.8, respectively. Primary (100% vs. 92%) and
      secondary (100% vs. 96%) iliofemoral patency rates and presence of femoro
      popliteal venous reflux (39% vs. 33%) were similar in both groups. Conclusion The
      addition of intravascular ultrasound energy to conventional CDT for the treatment
      of acute IFDVT did not have any impact on relevant clinical or duplex sonographic
      outcomes, which were favorable in both study groups. Clinical Trial Registration
      URL: http://www.clinicaltrials.gov. Unique identifier:NCT01482273.

PMID- 28440042
TI  - Biodegradable hydrogel-based biomaterials with high absorbent properties for non
      adherent wound dressing.
AB  - Dressing materials involve conventional gauzes and modern materials such as
      hydrogels and foam-based biomaterials. Although the choice of dressing material
      depends on the type of wound, a dressing material is expected to be non
      cytotoxic. Additionally, moist dressing is considered appropriate to accelerate
      epithelialisation, while dry dressing may cause tissue damage during removal. An
      ideal dressing material is expected to provide a moist environment and degrade
      and release the drug for faster wound healing. Thus, we have designed a hydrogel
      based biodegradable dressing material to provide the moist environment with no
      cytotoxic effect in vitro. The design of the hydrogel involved alginate-collagen
      reinforced with whisker cellulose derived from cotton. The hydrogel was prepared
      via amide linkage in the presence of 1-ethyl-(dimethylaminopropyl) carbodiimide
      (EDC) and N-hydroxysulfosuccinimide (NHS), followed by divalent cationic cross
      linking of alginate and hydrogen bonding with cellulose. The high water retention
      capability of the hydrogel enables a moist environment to be maintained in the
      wounded area. The constituents of the hydrogel provided a microenvironment that
      was suitable for cell proliferation in the vicinity of the hydrogel but inhibited
      cell attachment on it. The MTT assay results indicated a higher fibroblast
      proliferation and viability in the presence of the hydrogel.

PMID- 28440043
TI  - Self-Sealed Bionic Long Microchannels with Thin Walls and Designable Nanoholes
      Prepared by Line-Contact Capillary-Force Assembly.
AB  - Long microchannels with thin walls, small width, and nanoholes or irregular
      shaped microgaps, which are similar to capillaries or cancerous vessels, are
      urgently needed to simulate the physiological activities in human body. However,
      the fabrication of such channels remains challenging. Here, microchannels with
      designable holes are manufactured by combining laser printing with line-contact
      capillary-force assembly. Two microwalls are first printed by femtosecond laser
      direct-writing, and subsequently driven to collapse into a channel by the
      capillary force that arises in the evaporation of developer. The channel can
      remain stable in solvent due to the enhanced Van der Waals' force caused by the
      line-contact of microwalls. Microchannels with controllable nanoholes and almost
      arbitrary patterns can be fabricated without any bonding or multistep processes.
      As-prepared microchannels, with wall thicknesses less than 1 um, widths less than
      3 um, lengths more than 1 mm, are comparable with human capillaries. In addition,
      the prepared channels also exhibit the ability to steer the flow of liquid
      without any external pump.

PMID- 28440044
TI  - Mental illness and bariatric surgery.

PMID- 28440046
TI  - Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in
      Postmenopausal Women with Obesity.
AB  - OBJECTIVE: Abdominal fat accumulation after menopause is associated with low
      grade inflammation and increased risk of metabolic disorders. Effective long-term
      lifestyle treatment is therefore needed. METHODS: Seventy healthy postmenopausal
      women (age 60 +/- 5.6 years) with BMI 32.5 +/- 5.5 were randomized to a
      Paleolithic-type diet (PD) or a prudent control diet (CD) for 24 months. Blood
      samples and fat biopsies were collected at baseline, 6 months, and 24 months to
      analyze inflammation-related parameters. RESULTS: Android fat decreased
      significantly more in the PD group (P = 0.009) during the first 6 months with
      weight maintenance at 24 months in both groups. Long-term significant effects (P
      < 0.001) on adipose gene expression were found for toll-like receptor 4
      (decreased at 24 months) and macrophage migration inhibitory factor (increased at
      24 months) in both groups. Serum interleukin 6 (IL-6) and tumor necrosis factor
      alpha levels were decreased at 24 months in both groups (P < 0.001) with a
      significant diet-by-time interaction for serum IL-6 (P = 0.022). High-sensitivity
      C-reactive protein was decreased in the PD group at 24 months (P = 0.001).
      CONCLUSIONS: A reduction of abdominal obesity in postmenopausal women is linked
      to specific changes in inflammation-related adipose gene expression.

PMID- 28440045
TI  - Coadministration of lorcaserin and phentermine for weight management: A 12-week,
      randomized, pilot safety study.
AB  - OBJECTIVE: To assess the short-term tolerability of lorcaserin alone or with two
      dose regimens of phentermine. METHODS: This was a 12-week, randomized, double
      blind, pilot safety study of N = 238 nondiabetic patients with obesity or
      overweight with >=1 comorbidity randomized to lorcaserin 10 mg twice daily (BID;
      LOR BID) alone or with phentermine 15 mg once daily (QD; LOR BID+PHEN QD) or 15
      mg twice daily (LOR BID+PHEN BID). Patients reporting >= 1 of 9 potentially
      serotonergic adverse events (AEs), mean weight loss (WL), and >=5% WL are
      reported. RESULTS: N = 238 were randomized, and N = 235 were treated. N = 94
      reported potentially serotonergic AEs: 37.2% LOR BID, 42.3% LOR BID+PHEN QD, and
      40.5% LOR BID+PHEN BID. AEs leading to discontinuation were reported
      approximately twice as often in the LOR BID+PHEN BID group versus the LOR BID
      group. Mean WL was 3.5 kg/3.3%, 7.0 kg/6.7%, and 7.6 kg/7.2% for LOR BID, LOR
      BID+PHEN QD, and LOR BID+PHEN BID, respectively. At least 5% WL was achieved by
      28.2% LOR BID, 59.0% LOR BID+PHEN QD (P = 0.0002 vs. LOR BID), and 70.9% LOR
      BID+PHEN BID (P < 0.0001 vs. LOR BID) patients. CONCLUSIONS: Phentermine added to
      lorcaserin enhanced short-term weight loss but did not increase incidence of
      potentially serotonergic AEs; however, phentermine twice daily increased
      discontinuation compared to both lorcaserin alone and lorcaserin plus phentermine
      once daily.

PMID- 28440047
TI  - Mental illness in bariatric surgery: A cohort study from the PORTAL network.
AB  - OBJECTIVE: To compare bariatric surgery outcomes according to preoperative mental
      illness category. METHODS: Electronic health record data from several US
      healthcare systems were used to compare outcomes of four groups of patients who
      underwent bariatric surgery in 2012 and 2013. These included the following:
      people with (1) no mental illness, (2) mild-to-moderate depression or anxiety,
      (3) severe depression or anxiety, and (4) bipolar, psychosis, or schizophrenia
      spectrum disorders. Groups were compared on weight loss trajectory using
      generalized estimating equations using B-spline bases and on all-cause emergency
      department visits and hospital days using zero-inflated Poisson and negative
      binomial regression up to 2 years after surgery. Models were adjusted for
      demographic and health covariates, including baseline healthcare use. RESULTS:
      Among 8,192 patients, mean age was 44.3 (10.7) years, 79.9% were female, and
      45.6% were white. Fifty-seven percent had preoperative mental illness. There were
      no differences between groups for weight loss, but patients with preoperative
      severe depression or anxiety or bipolar, psychosis, or schizophrenia spectrum
      disorders had higher follow-up levels of emergency department visits and hospital
      days compared to those with no mental illness. CONCLUSIONS: In this multicenter
      study, mental illness was not associated with differential weight loss after
      bariatric surgery, but additional research could focus on reducing acute care use
      among these patients.

PMID- 28440048
TI  - Ability to adjust nocturnal fat oxidation in response to overfeeding predicts 5
      year weight gain in adults.
AB  - OBJECTIVE: To determine whether metabolic responses to short-term overfeeding
      predict longitudinal changes in body weight. METHODS: Twenty-four-hour energy
      expenditure (EE) and substrate utilization were measured at baseline in a room
      calorimeter following 3 days of eucaloric and hypercaloric feeding (40% excess)
      in a sample of lean adults (n: 34; age: 28 +/- 2 y; BMI: 22 +/- 3 kg/m2 ). Body
      mass and fat mass (dual-energy x-ray absorptiometry) were measured annually for 5
      years. Regression analyses examined whether changes in EE and fuel use with
      overfeeding predicted body weight and composition changes over 5 years. RESULTS:
      Overfeeding increased EE and reduced fat oxidation when examined over the 24
      hour, waking, and nocturnal periods. Absolute change in body mass over 5 years
      was 3.0 +/- 0.6 kg (average rate of change = 0.7 +/- 0.1 kg/y, P < 0.001). Lower
      nocturnal (but not 24-hour or waking) fat oxidation (r = -0.42, P = 0.01) and EE
      (r = -0.33, P = 0.05) with overfeeding were the strongest predictors of 5-year
      weight gain. When adjusted for covariates, changes in nocturnal fat oxidation and
      EE with overfeeding predicted 41% of the variance in weight change (P = 0.02).
      CONCLUSIONS: Failure to maintain fat oxidation at night following a period of
      overfeeding appears to be associated with a metabolic phenotype favoring weight
      gain.

PMID- 28440049
TI  - Analytical-Based Methodologies for Examining the In Vitro Absorption,
      Distribution, Metabolism, and Elimination (ADME) of Silver Nanoparticles.
AB  - The clinical applications of silver nanoparticles (AgNPs) remain limited due to
      the lack of well-established methodologies for studying their nanokinetics.
      Hereby, the primary goal is to adapt a suite of analytical-based methodologies
      for examining the in vitro absorption, distribution, metabolism, and elimination
      of AgNPs. Vero 76 and HEK 293 cells are exposed to ~10-nm spherical AgNPs+ and
      AgNPs- at relevant concentrations (0-300 ug mL-1 ) and times (4-48 h).
      Absorption: Inductively coupled plasma optical emission spectroscopy (ICP-OES)
      demonstrates that the two AgNP formulations are not bioequivalent. For example,
      different bioavailabilities (Cmaximum < 20.7 +/- 4% and 6.82 +/- 0.4%),
      absorption times (Tmaximum > 48 and ~24 h), and absorption rate laws (first- and
      zeroth-order at 300 ug mL-1 ) are determined in Vero 76 for AgNPs+ and AgNPs- ,
      respectively. Distribution: Raman and CytoViva hyperspectral imaging show
      different cellular localizations for AgNPs+ and AgNPs- . Metabolism: Cloud point
      extraction (CPE)-tangential flow filtration (TFF) reveal that <= 11% +/- 4% of
      the administered, sublethal AgNPs release Ag+ and contribute to the observed
      cytotoxicity. Elimination: ICP-OES-CPE suggests that AgNPs are cleared via
      exocytosis.

PMID- 28440050
TI  - Enzymatic debridement with collagenase in wounds and ulcers: a systematic review
      and meta-analysis.
AB  - Enzymatic debridement with collagenase is a technique that is commonly used in
      clinical practice. This systematic review examines the effect of collagenase on
      all kinds of wounds, compared to an alternative therapy, on wound healing, wound
      bed characteristics, cost-effectiveness and the occurrence of adverse events. We
      conducted a systematic literature search on available literature in Cochrane
      databases, MEDLINE, EMBASE and CINAHL. Two investigators independently assessed
      the titles and abstracts of all randomised controlled trials obtained involving
      collagenase of all kinds of wounds based on inclusion criteria. Of the 1411
      citations retrieved, 22 studies reported outcomes with the use of collagenase
      either for wound healing or wound debridement. Results support the use of
      collagenase for enzymatic debridement in pressure ulcers, diabetic foot ulcers
      and in conjunction with topical antibiotics for burns. However, studies presented
      a high risk of bias. Risk ratio of developing an adverse event related to
      collagenase versus the alternative treatment was statistically significant (for
      10 studies, RR: 1.79, 95% CI 1.24-2.59, I2 =0%, P = 0.002). There is very limited
      data on the effect of collagenase as an enzymatic debridement technique on
      wounds. More independant research and adequate reporting of adverse events are
      warranted.

PMID- 28440051
TI  - Targeting NTRK fusions for the treatment of congenital mesoblastic nephroma.

PMID- 28440052
TI  - Doctoral profile of the medical radiation sciences: a baseline for Australia and
      New Zealand.
AB  - INTRODUCTION: Research is critical to evidence-based practice, and the rapid
      developments in technology provide opportunities to innovate and improve
      practice. Little is known about the research profile of the medical radiation
      science (MRS) profession in Australia and New Zealand (NZ). This study provides a
      baseline of their doctoral activity. METHODS: A cross-sectional survey of MRS
      professionals in Australia and NZ holding a doctorate or undertaking doctoral
      studies, was performed using an online tool (Bristol Online Survey(r) , Bristol,
      UK). A chain-referral sampling technique was adopted for data collection. An
      email invitation with a link to the survey was generated and distributed through
      email and social media. The survey contained questions related to participant
      demographics, doctoral status, qualification route, funding and employment.
      RESULTS: There were 63 responses to the survey comprising 50.8% diagnostic
      radiographers (DRs; n = 32), 23.8% radiation therapists (RTs; n = 15), with the
      remaining 25.4% (n = 16) equally split between sonographers and nuclear medicine
      technologists (NMTs). A total of 40 (63.5%) of respondents had completed their
      doctoral qualification. In NZ, only DRs held a doctoral award constituting 0.3%
      of DRs and 0.2% of the total registered MRS population. In Australia, there was a
      greater proportion of doctoral NMTs (n = 8/1098; 0.7%) than RTs (n = 15/2394;
      0.6%) and DRs (n = 27/12,001; 0.2%). CONCLUSION: Similar to other countries,
      findings show a very small percentage of doctoral MRS professionals in Australia
      and NZ. Strategies to engage and support individuals in research, up to and
      beyond doctoral study, need to be embedded in practice.

PMID- 28440054
TI  - A new approach to obtain cellulose nanocrystals and ethanol from eucalyptus
      cellulose pulp via the biochemical pathway.
AB  - The feasibility of integration of cellulosic ethanol production with the
      manufacture of cellulose nanofibers (CNF) and cellulose nanocrystals (CNC) was
      evaluated using eucalyptus cellulose pulp as feedstock and employing the
      biochemical route alone. For the enzymatic hydrolysis step, experimental central
      composite design (CCD) methodology was used as a tool to evaluate the effects of
      solids loading (SL) and enzymatic loading (EL) on glucose release and cellulose
      conversion. Glucose concentrations from 45 to 125 g/L were obtained after 24 h,
      with cellulose conversions from 35 to 96%. Validation of the statistical model
      was performed at SL of 20% and EL of 10 mg protein/g, which was defined by the
      desirability function as the optimum condition. The sugars released were used for
      the production of ethanol by Saccharomyces cerevisiae, resulting in 62.1 g/L
      ethanol after 8 h (yield of 95.5%). For all the CCD experimental conditions, the
      residual solids presented CNF characteristics. Moreover, the use of a new
      strategy with temperature reduction from 50 to 35 degrees C after 24 h of
      enzymatic hydrolysis enabled CNC to be obtained after 144 h. The CNC showed a
      crystallinity index of 83%, length of 260 nm, diameter of 15 nm, and aspect ratio
      (L/D) of 15. These characteristics are suitable for many applications, such as
      reinforcement in polymeric materials and other lower volume higher value bio
      based products. The findings indicate the viability of obtaining ethanol and CNC
      using the biochemical route exclusively, potentially contributing to the future
      implementation of forest biorefineries. (c) 2017 American Institute of Chemical
      Engineers Biotechnol. Prog., 33:1085-1095, 2017.

PMID- 28440055
TI  - Microbial therapeutics: An annotated selection of World Wide Web sites relevant
      to the topics in microbial biotechnology.

PMID- 28440056
TI  - Counteracting Blueshift Optical Absorption and Maximizing Photon Harvest in
      Carbon Nitride Nanosheet Photocatalyst.
AB  - Blueshift of optical absorption and corresponding widening of the bandgap is a
      fundamental problem with 2D carbon nitride nanosheets (CNNS). An additional
      problem is low quantum yields (<9%) due to higher loss of absorbed photons. These
      problems impose a significant restriction to photocatalytic performance of CNNS.
      Therefore, the synthesis of narrow bandgap CNNS with high quantum efficiency is
      of pressing research importance. This contribution reports melem-derived narrow
      bandgap CNNS with a record-low bandgap of 2.45 eV. The narrowing in bandgap comes
      with improved optical absorption and use of visible-light photons together with
      excellent charge transport dynamics. This is demonstrated by a record high
      hydrogen evolution rate of 863 umol h-1 with apparent quantum efficiency of 16%
      at 420 nm.

PMID- 28440058
TI  - Atypical inter-hemispheric communication correlates with altered motor inhibition
      during learning of a new bimanual coordination pattern in developmental
      coordination disorder.
AB  - Impairment of motor learning skills in developmental coordination disorder (DCD)
      has been reported in several studies. Some hypotheses on neural mechanisms of
      motor learning deficits in DCD have emerged but, to date, brain-imaging
      investigations are scarce. The aim of the present study is to assess possible
      changes in communication between brain areas during practice of a new bimanual
      coordination task in teenagers with DCD (n = 10) compared to matched controls (n
      = 10). Accuracy, stability and number of mirror movements were computed as
      behavioural variables. Neural variables were assessed by electroencephalographic
      coherence analyses of intra-hemispheric and inter-hemispheric fronto-central
      electrodes. In both groups, accuracy of the new coordination increased
      concomitantly with right intra-hemispheric fronto-central coherence. Compared to
      typically developing teenagers, DCD teenagers presented learning difficulties
      expressed by less stability, no stabilization of the new coordination and a
      greater number of mirror movements despite practice. These measures correlated
      with reduced inter-hemispheric communication, even after practice of the new
      coordination. For the first time, these findings provide neuro-imaging evidence
      of a kind of inter-hemispheric 'disconnection' related to altered inhibition of
      mirror movements during motor learning in DCD.

PMID- 28440057
TI  - Overcoming Linsitinib intrinsic resistance through inhibition of nuclear factor
      kappaB signaling in esophageal squamous cell carcinoma.
AB  - The aim of this study is to evaluate the efficacy of insulin-like growth factor 1
      receptor (IGF-1R) inhibitor Linsitinib, in esophageal squamous cell carcinoma
      (ESCC), and to characterize special biomarker to screen Linsitinib-sensitive
      patients as well as explore the molecular-resistant mechanism to Linsitinib in
      ESCC. Our study evaluated the sensitivity of insulin-like growth factor 1
      receptor (IGF-1R) inhibitor, Linsitinib in ESCC cells with MTT assay. After
      Linsitinib treatment, the expressions of downstream signaling molecules and
      apoptosis pathways were measured by western blot. And the antitumor effect of
      Linsitinib and JSH-23, an inhibitor of nuclear factor-kappaB transcriptional
      activity, was analyzed both as single agent and in combination in ESCC.
      Apoptosis, cell viability, and clonogenic survival analysis were also
      investigated. The sensitivity of Linsitinib was relatively variable in patient
      derived primary ESCC cells as well as in human commercial cell lines. And the
      downstream AKT/mTOR and ERK signaling pathways were inhibited by Linsitinib,
      while phosphorylation level of NF-kappaB p65 was obviously activated to reduce
      apoptosis effect in Linsitinib-resistant cell lines. Most importantly, blockage
      of NF-kappaB activity by JSH-23 could sensitize resistant cells to Linsitinib
      treatment. Results from this study demonstrated that the intrinsic resistance to
      Linsitinib was predominantly mediated by NF-kappaB activation in ESCC. Moreover,
      combination of Linsitinib and JSH-23 as therapy provides a novel strategy to
      overcome resistance to Linsitinib in ESCC.

PMID- 28440059
TI  - Production of itaconic acid from pentose sugars by Aspergillus terreus.
AB  - Itaconic acid (IA), an unsaturated 5-carbon dicarboxylic acid, is a building
      block platform chemical that is currently produced industrially from glucose by
      fermentation with Aspergillus terreus. However, lignocellulosic biomass has
      potential to serve as low-cost source of sugars for production of IA. Research
      needs to be performed to find a suitable A. terreus strain that can use
      lignocellulose-derived pentose sugars and produce IA. One hundred A. terreus
      strains were evaluated for the first time for production of IA from xylose and
      arabinose. Twenty strains showed good production of IA from the sugars. Among
      these, six strains (NRRL strains 1960, 1961, 1962, 1972, 66125, and DSM 23081)
      were selected for further study. One of these strains NRRL 1961 produced 49.8 +/-
      0.3, 38.9 +/- 0.8, 34.8 +/- 0.9, and 33.2 +/- 2.4 g IA from 80 g glucose, xylose,
      arabinose and their mixture (1:1:1), respectively, per L at initial pH 3.1 and 33
      degrees C. This is the first report on the production of IA from arabinose and
      mixed sugar of glucose, xylose, and arabinose by A. terreus. The results
      presented in the article will be very useful in developing a process technology
      for production of IA from lignocellulosic feedstocks. (c) 2017 American Institute
      of Chemical Engineers Biotechnol. Prog., 33:1059-1067, 2017.

PMID- 28440060
TI  - A practical approach in bioreactor scale-up and process transfer using a
      combination of constant P/V and vvm as the criterion.
AB  - Bioreactor scale-up is a critical step in the production of therapeutic proteins
      such as monoclonal antibodies (MAbs). With the scale-up criterion such as similar
      power input per volume or O2 volumetric mass transfer coefficient ( kLa),
      adequate oxygen supply and cell growth can be largely achieved. However, CO2
      stripping in the growth phase is often inadequate. This could cascade down to
      increased base addition and osmolality, as well as residual lactate increase and
      compromised production and product quality. Here we describe a practical approach
      in bioreactor scale-up and process transfer, where bioreactor information may be
      limited. We evaluated the sparger kLa and kLaCO2 (CO2 volumetric mass transfer
      coefficient) from a range of bioreactor scales (3-2,000 L) with different
      spargers. Results demonstrated that kLa for oxygen is not an issue when scaling
      from small-scale to large-scale bioreactors at the same gas flow rate per reactor
      volume (vvm). Results also showed that sparging CO2 stripping, kLaCO2, is
      dominated by the gas throughput. As a result, a combination of a minimum constant
      vvm air or N2 flow with a similar specific power was used as the general scale-up
      criterion. An equation was developed to determine the minimum vvm required for
      removing CO2 produced from cell respiration. We demonstrated the effectiveness of
      using such scale-up criterion with five MAb projects exhibiting different cell
      growth and metabolic characteristics, scaled from 3 to 2,000 L bioreactors across
      four sites. (c) 2017 American Institute of Chemical Engineers Biotechnol. Prog.,
      33:1146-1159, 2017.

PMID- 28440053
TI  - Who is at risk of death from nephrectomy? An analysis of thirty-day mortality
      after 21 380 nephrectomies in 3 years of the British Association of Urological
      Surgeons (BAUS) National Nephrectomy Audit.
AB  - OBJECTIVE: To ascertain contemporary overall and differential thirty-day
      mortality (TDM) rates after all types of nephrectomy in the UK, and to identify
      potential new risk factors for death. PATIENTS AND METHODS: We conducted a
      retrospective analysis of the 110 deaths that occurred within 30 days of surgery
      out of the total of 21 380 nephrectomies performed, and calculated the odds ratio
      (OR) and 95% confidence interval (CI) for TDM based on peri-operative
      characteristics. RESULTS: The overall TDM rate was 110/21380 (0.5%). The TDM
      rates after radical, partial, simple nephrectomy and nephro-ureterectomy were
      0.6% (63/11057), 0.1% (4/3931), 0.4% (11/2819) and 0.9% (28/3091), respectively.
      TDM increased with age, stage, estimated blood loss (EBL), operating time and
      performance status. EBL of 1-2 L was associated with a greater risk of TDM than
      EBL of 2-5 L (OR 1.38; 95% CI 1.03-2.24). Conversion from minimally invasive
      surgery was associated with higher risk than non-conversion (OR 2.53; 95% CI 1.14
      4.51. Curative surgery was safer than cytoreductive surgery (OR 0.31; 95% CI 0.18
      0.54). There was an association between surgical volume and TDM. CONCLUSIONS:
      This study provides contemporary insights into the true risks of all types of
      nephrectomy. The TDM rate after nephrectomy in the UK appears acceptably low at
      0.5%. Established risk factors were confirmed and the following novel risk
      factors were identified: modest EBL (1-2 L) and conversion from minimally
      invasive surgery.

PMID- 28440061
TI  - Maori gene and epigenetics hypotheses: the temptation of population genetics.

PMID- 28440062
TI  - Predictive value of serum sST2 in preschool wheezers for development of asthma
      with high FeNO.
AB  - Wheezing is common in childhood. However, current prediction models of pediatric
      asthma have only modest accuracy. Novel biomarkers and definition of
      subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1
      (IL1RL1 or ST2) is a well-replicated asthma gene and associates with
      eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with
      elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index
      (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3
      years-old wheezers do not predict doctors' diagnosed asthma at age 6 years.
      Instead, sST2 predicts a subphenotype of asthma characterized by increased levels
      of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the
      predictive value of the API (AUC=0.70, 95% CI 0.56-0.84), but had also
      significant predictive value on its own (AUC=0.65, 95% CI 0.52-0.79). Our study
      indicates that sST2 in preschool wheezers has predictive value for the
      development of eosinophilic airway inflammation in asthmatic children at school
      age.

PMID- 28440063
TI  - Micronuclei and nuclear buds: Highlighting overlooked indicators of chromosomal
      damage in thyroid aspiration smears.
AB  - BACKGROUND: We aimed to examine the diagnostic utility of micronuclei (MN) and
      nuclear buds (NBs) in aspiration smears of the well-differentiated epithelial
      lesions of thyroid. METHODS: One hundred five cases composed of 34 follicular
      nodular disease (FND), 31 Hashimoto's thyroiditis (HT), and 40 papillary thyroid
      carcinoma (PTC) were compiled retrospectively. May- Grunwald Giemsa (MGG) stained
      smears of each case were selected to count cells with nuclear protrusions (NPs)
      per 1000 cells. The frequency of cells with NPs (MN&NBs) was compared by using
      Mann-Whitney U test and Kruskal-Wallis tests when appropriate. Post-Hoc Tukey
      test was used for pairwise comparison of different diagnostic categories. By
      running a ROC curve analysis, diagnostic usefulness of the frequency of cells
      with NPs (MN&NBs) and their cut-off values to predict malignant behavior were
      calculated. P < 0.05 was regarded as significant. RESULTS: NPs (MN&NBs) were
      significantly more frequent in malignant cases than benign ones. NBs were more
      frequent in conventional PTC compared to FV of PTC, but the frequency of MN did
      not significantly differ between these. ROC curve analysis revealed that
      evaluation of the frequency of cells with NPs (MN&NBs) was a highly specific,
      sensitive, and diagnostically useful method to identify malignant behavior.
      CONCLUSION: To the best of our knowledge, this is the first study in the
      literature to evaluate the frequency of cells with NPs (MN&NBs) in human thyroid
      aspiration smears. Our results show that evaluation of NPs (MN&NBs) may be a
      useful diagnostic tool to detect PTC in thyroid aspiration smears. Diagn.
      Cytopathol. 2017;45:673-680. (c) 2017 Wiley Periodicals, Inc.

PMID- 28440064
TI  - Synthetic and analytical strategies for the quantification of phenyl-gamma
      valerolactone conjugated metabolites in human urine.
AB  - SCOPE: The contribution of the gut microbiota to the metabolism of catechins and
      proanthocyanidins remains unclear. Phenyl-gamma-valerolactones have been
      identified as the most representative metabolites of these dietary flavan-3-ols,
      but their accurate quantification has posed problems because of a lack of
      appropriate bioanalytical standards. This work aimed at synthesizing a novel set
      of sulphate- and glucuronide-conjugated phenyl-gamma-valerolactones and at
      developing an analytical platform using UHPLC-ESI-MS/MS for their quantification
      in urine. METHODS AND RESULTS: Eight glucuronide and sulphate conjugates of
      hydroxyphenyl-gamma-valerolactones were synthesized and used as analytical
      standards, together with five phenyl-gamma-valerolactone aglycones, for the
      development of a high-throughput, validated analytical method. Chromatographic
      and MS conditions were optimized. The method validation showed acceptable
      linearity, intra-day and inter-day repeatability, and accuracy, with the
      analytical range, limit of detection (LOD), and lower limit of quantification
      (LLOQ) varying notably among compounds. The method was used to calculate the
      excretion of phenyl-gamma-valerolactones in healthy subject consuming green tea,
      providing novel information on the real concentrations of phenyl-gamma
      valerolactones in urine. CONCLUSION: This work opens the door to better studying
      the bioavailability of flavan-3-ols and the real exposition to flavan-3-ol
      sources, as well as to define the bioactivity of these colonic metabolites in
      cell assays.

PMID- 28440065
TI  - Contribution to the discussion of "A critical evaluation of the current 'p-value
      controversy"'.

PMID- 28440066
TI  - Elevated glypican-1 expression is associated with an unfavorable prognosis in
      pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in humans, with
      a 5-year survival rate of <5%. Recently, glypican-1 (GPC1)-expressing circulating
      exosomes were found to be a promising diagnostic tool for PDAC. However, the
      aberrant expression of GPC1 has not been systematically evaluated in large-scale
      clinical samples of PDAC. Here, we performed a comprehensive analysis of GPC1
      mRNA and protein expression features. Included in this study were 178 PDAC
      patients from the cancer genome atlas (TCGA) and 186 subjects whose tissues were
      used in immunohistochemical staining assays. We demonstrated that GPC1 mRNA was
      silenced in normal pancreata; however, it was re-expressed in PDAC tissues
      probably because of the promoter hypomethylation. The GPC1 protein was barely
      expressed in the normal and adjacent noncancerous pancreata. In tumor tissues,
      59.7% (111/186) of the detected samples showed positive expression. Notably, GPC1
      was elevated in 63.6% (34/55) of early stage cases. High levels of GPC1 were
      associated with poorer differentiation and larger tumor diameters. Kaplan-Meier
      analysis showed a significant difference in overall survival between the groups
      categorized by GPC1 expression (P = 0.0028). Multivariate analyses indicated that
      GPC1 was a significant risk factor for poor overall survival with a 1.82-fold
      increase in the hazard ratio (P = 0.0022). In conclusion, during pancreatic
      tumorigenesis, GPC1 was ectopically expressed and served as an independent poor
      prognostic factor. Our findings highlighted the alluring prospect of GPC1 as an
      early diagnostic and prognostic marker as well as a therapeutic target for PDAC.

PMID- 28440067
TI  - Real-life data regarding acute procedural success and 1-year clinical outcome of
      desolve bioresorbable scaffolds.
AB  - OBJECTIVES: We aimed to evaluate the peri-procedural success of DESolve bio
      resorbable scaffolds (BRSs) and analyzed real-life data about major cardiac
      events during 1-year follow-up. BACKGROUND: There is little information about
      real-life data of DESolve BRS which is a novel stent technology offering various
      advantages over drug eluting stents and commonly used in daily cardiology
      practice. METHODS: We conducted this single-center and non-randomized cross
      sectional study from June 2015 through August 2016 in Medipol University
      Department of Cardiology and included 117 patients undergoing single or
      multivessel percutaneous coronary interventions (PCI) with novolimus-eluting BRS
      devices (152 scaffolds) (Elixir Medical Corporation). Study end points were acute
      device and procedural success, scaffold thrombosis and major adverse cardiac
      event (MACE) rates of DESolve BRS. RESULTS: Device success was 96.7% and
      procedural success was 99.3%. We detected MACE rate as 0.9% while clinical-driven
      target lesion revascularization was performed in one patient. None of the
      patients experienced scaffold thrombosis or death. Peri-procedural complications
      were reported in three patients. CONCLUSIONS: High rates of successful scaffold
      implantations, low rates of peri-procedural complications, and major cardiac
      events in long-term suggest that DESolve scaffolds can safely and effectively be
      used in daily intervention practice by particularly experienced operators.

PMID- 28440069
TI  - Occult cancer-related first venous thromboembolism is associated with an
      increased risk of recurrent venous thromboembolism.
AB  - : Essentials Recurrence risk after an occult cancer-related incident venous
      thromboembolism (VTE) is unknown. We compared the risk of VTE recurrence in
      occult-, overt- and non-cancer related first VTE. Patients with occult-cancer
      related first VTE had the highest risk of VTE recurrence. The high recurrence
      risk in occult cancer is likely due to the advanced cancers. SUMMARY: Background
      Although venous thromboembolism (VTE) is associated with a high recurrence rate,
      the absolute recurrence rates for cancer-related VTE, particularly occult cancer,
      are not well known. Objectives To investigate the risk of VTE recurrence in
      patients with occult and overt cancer-related VTE. Methods Incident VTE events
      among participants of the first to sixth Tromso surveys occurring in the period
      1994-2012 were included. Occult cancer was defined as cancer diagnosed within a
      year following a VTE, and overt cancer was defined as cancer diagnosed within the
      2 years before a VTE. Results Among 733 patients with incident VTE, 110 had overt
      cancer and 40 had occult cancer. There were 95 recurrent VTE events during a
      median of 3.2 years of follow-up. The 1-year cumulative incidence of VTE
      recurrence was 38.6% in subjects with occult cancer, 15.5% in subjects with overt
      cancer, and 3.8% in non-cancer subjects. The 1-year risk of recurrence was 12
      fold (hazard ratio [HR] 12.4, 95% confidence interval [CI] 5.9-26.3) higher in
      subjects with occult cancer and four-fold (HR 4.3, 95% CI 2.0-9.2) higher in
      subjects with overt cancer than in non-cancer subjects. The occult cancers
      associated with VTE recurrence were typically located at prothrombotic sites
      (i.e. lung and gastrointestinal) and presented at advanced stages. The majority
      (69%) of recurrences in subjects with occult cancer occurred before or shortly
      after cancer diagnosis, and were therefore not treatment-related. Conclusion Our
      findings suggest that the increased risk of recurrence in patients with occult
      cancer is mainly attributable to the advanced cancers in these patients.

PMID- 28440068
TI  - Correlates of verbal and physical aggression among patrons of licensed venues in
      Australia.
AB  - INTRODUCTION AND AIMS: The current study aimed to examine the association between
      patron demographics and substance use, and experiences of verbal and physical
      aggressive incidents within the last 3 months among patrons of night-time
      entertainment precincts (NEP) in Australia. DESIGN AND METHODS: Patron interviews
      (n = 4216) were conducted around licensed venues in the NEPs of five Australian
      cities. Seven correlates of verbal and physical aggressive incidents were
      examined: gender, age, occupation, blood alcohol concentration, pre-drinking,
      energy drink use and illicit drug use in the current session. RESULTS: A total of
      7.5% and 8.2% of respondents reported involvement in a verbally and physically
      aggressive incident in the past 3 months, respectively. Multivariate logistic
      regression models indicated men and people <25 years old were significantly more
      likely to report both verbal and physical aggressive incidents. A significant
      occupation effect showed lower levels of both verbal and physical aggression in
      managers/professionals compared with non-office workers. The likelihood of being
      involved in a verbally aggressive incident significantly increased with energy
      drink consumption, while the likelihood of being involved in a physically
      aggressive incident significantly increased with blood alcohol concentration,
      energy drink consumption and illicit drug use. DISCUSSION AND CONCLUSIONS: This
      study highlights the different correlates of verbal and physical aggression
      within NEPs, suggesting they should be viewed as distinct types of violence,
      rather than points on a continuum. Major modifiable correlates with verbal and
      physical aggression included intoxication, energy drink consumption, and illicit
      drug use, suggesting the need for further interventions and policy development to
      address these key issues. [Hyder S, Coomber K, Pennay A, Droste N, Curtis A,
      Mayshak R, Lam T, Gilmore W, Chikritzhs T, Miller PG. Correlates of verbal and
      physical aggression among patrons of licensed venues in Australia. Drug Alcohol
      Rev 2018;37:6-13].

PMID- 28440070
TI  - Chiral analysis of amphetamines in hair by liquid chromatography-tandem mass
      spectrometry: compliance-monitoring of attention deficit hyperactivity disorder
      (ADHD) patients under Elvanse(r) therapy and identification after controlled low
      dose application.
AB  - Amphetamine (AMP) is used as an illicit drug and also for the treatment of
      attention deficit hyperactivity disorder (ADHD). Respective drugs most often
      contain the enantiomer (S)-AMP as active compound or (S)-AMP is formed from the
      prodrug lisdexamfetamine (Elvanse(r)) whereas the illicit drug is usually traded
      as racemate ((R/S)-AMP). A differentiation between the use of the medically
      prescribed drug and the abuse of illicit street amphetamine is of great
      importance, for example in retrospective consumption monitoring by hair analysis.
      A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the chiral
      separation and quantitation of (S)- and (R)-AMP in hair was developed. For this
      purpose, 20 mg hair was extracted and derivatized with N-(2,4-dinitro-5
      fluorophenyl)-L(S)-valinamide L(S)-(DNPV) to yield amphetamine diastereomers.
      Baseline separation of the resulting diastereomers was achieved on a high
      pressure liquid-chromatography system (HPLC) coupled to a Sciex QTRAP(r) 5500
      linear ion trap quadrupole mass spectrometer. The method was successfully
      validated. Analysis of hair samples from nine Elvanse(r) patients revealed only
      (S)-AMP in eight cases; one subject showed both enantiomers indicating a (side-)
      consumption of street amphetamine. The analysis of the 16 amphetamine users'
      samples showed only racemic amphetamine. Furthermore, it could be shown in a
      controlled study that (S)-AMP can be detected after administration of even very
      low doses of lisdexamfetamine and dexamphetamine, which can be of interest in
      forensic toxicology and especially in drug-facilitated crime (DFC). The method
      now enables the retrospective compliance-monitoring of ADHD patients and the
      differentiation between medically prescribed intake of (S)-amphetamine and abuse
      of illicit street amphetamine.

PMID- 28440071
TI  - Abstracts of the HIV & Hepatitis in the Americas 2017 - Congress.

PMID- 28440072
TI  - Efficient Bulk Heterojunction CH3NH3PbI3-TiO2 Solar Cells with TiO2 Nanoparticles
      at Grain Boundaries of Perovskite by Multi-Cycle-Coating Strategy.
AB  - A novel bulk heterojunction (BHJ) perovskite solar cell (PSC), where the
      perovskite grains act as donor and the TiO2 nanoparticles act as acceptor, is
      reported. This efficient BHJ PSC was simply solution processed from a mixed
      precursor of CH3NH3PbI3 (MAPbI3) and TiO2 nanoparticles. With dissolution and
      recrystallization by multi-cycle-coating, a unique composite structure ranging
      from a MAPbI3-TiO2-dominated layer on the substrate side to a pure perovskite
      layer on the top side is formed, which is beneficial for the blocking of possible
      contact between TiO2 and the hole transport material at the interface. Scanning
      electron microscopy clearly shows that TiO2 nanoparticles accumulate along the
      grain boundaries (GBs) of perovskite. The TiO2 nanoparticles at the GBs quickly
      extract and reserve photogenerated electrons before they transport into the
      perovskite phase, as described in the multitrapping model, retarding the electron
      hole recombination and reducing the energy loss, resulting in increased VOC and
      fill factor. Moreover, the pinning effect of the TiO2 nanoparticles at the GBs
      from the strong bindings between TiO2 and MAPbI3 suppresses massive ion migration
      along the GBs, leading to improved operational stability and diminished
      hysteresis. Photoluminescence (PL) quenching and PL decay confirm the efficient
      exciton dissociation on the heterointerface. Electrochemical impedance
      spectroscopy and open-circuit photovoltage decay measurements show the reduced
      recombination loss and improved carrier lifetime of the BHJ PSCs. This novel
      strategy of device design effectively combines the benefits of both planar and
      mesostructured architectures whilst avoiding their shortcomings, eventually
      leading to a high PCE of 17.42% under 1 Sun illumination. The newly proposed
      approach also provides a new way to fabricate a TiO2-containing perovskite active
      layer at a low temperature.

PMID- 28440075
TI  - Synthesis of Six-Membered Carbo-/Heterocycles via Cascade Reaction of Alkynes and
      Diazo Compounds.
AB  - A novel approach toward diverse six-membered carbo-/heterocycles has been
      developed using diazo compounds and alkyne-substituted malonates as the suitable
      substrates. The polyfunctionalized cyclohexenes, tetrahydropyridines, and
      dihydropyrans have been prepared in moderate to high yield under mild reaction
      conditions. Importantly, the ligand plays a significant role in this copper
      catalyzed protocol.

PMID- 28440074
TI  - Applications of Synthetic Organic Tetrasulfides as H2S Donors.
AB  - In an effort to expand the availability of simple polysulfides for H2S donation,
      we report here the synthesis and H2S release profiles of bis(aryl) and bis(alkyl)
      tetrasulfides. The tetrasulfide donors release H2S in a first-order dependence on
      reduced glutathione (GSH) and release more H2S than the commonly used trisulfide
      DATS.

PMID- 28440073
TI  - Antiparallel Dynamic Covalent Chemistries.
AB  - The ability to design reaction networks with high, but addressable complexity is
      a necessary prerequisite to make advanced functional chemical systems. Dynamic
      combinatorial chemistry has proven to be a useful tool in achieving complexity,
      however with some limitations in controlling it. Herein we introduce the concept
      of antiparallel chemistries, in which the same functional group can be channeled
      into one of two reversible chemistries depending on a controllable parameter.
      Such systems allow both for achieving complexity, by combinatorial chemistry, and
      addressing it, by switching from one chemistry to another by controlling an
      external parameter. In our design the two antiparallel chemistries are thiol
      disulfide exchange and thio-Michael addition, sharing the thiol as the common
      building block. By means of oxidation and reduction the system can be reversibly
      switched from predominantly thio-Michael chemistry to predominantly disulfide
      chemistry, as well as to any intermediate state. Both chemistries operate in
      water, at room temperature, and at mildly basic pH, which makes them a suitable
      platform for further development of systems chemistry.

PMID- 28440076
TI  - Cell-Substrate Dynamics of the Epithelial-to-Mesenchymal Transition.
AB  - The biological process of the epithelial-to-mesenchymal transition (EMT) allows
      epithelial cells to enhance their migratory and invasive behavior and plays a key
      role in embryogenesis, fibrosis, wound healing, and metastasis. Among the
      multiple biochemical changes from an epithelial to a mesenchymal phenotype, the
      alteration of cellular dynamics in cell-cell as well as cell-substrate contacts
      is crucial. To determine these variations over the whole time scale of the EMT,
      we measure the cell-substrate distance of epithelial NMuMG cells during EMT using
      our newly established metal-induced energy transfer (MIET) microscopy, which
      allows one to achieve nanometer axial resolution. We show that, in the very first
      hours of the transition, the cell-substrate distance increases substantially, but
      later in the process after reaching the mesenchymal state, this distance is
      reduced again to the level of untreated cells. These findings relate to a change
      in the number of adhesion points and will help to better understand remodeling
      processes associated with wound healing, embryonic development, cancer
      progression, or tissue regeneration.

PMID- 28440078
TI  - Synthetic Route Development for the Laboratory Preparation of Eupalinilide E.
AB  - Following the discovery that the guaianolide natural product eupalinilide E
      promotes the expansion of hematopoietic stem and progenitor cells; the
      development of a synthetic route to provide laboratory access to the natural
      product became a priority. Exploration of multiple synthetic routes yielded an
      approach that has permitted a scalable synthesis of the natural product. Two
      routes that failed to access eupalinilide E were triaged either as a result of
      providing an incorrect diastereomer or due to lack of synthetic efficiency. The
      successful strategy relied on late-stage allylic oxidations at two separate
      positions of the molecule, which significantly increased the breadth of reactions
      that could be used to this point. Subsequent to C-H bond oxidation, adaptations
      of existing chemical transformations were required to permit chemoselective
      reduction and oxidation reactions. These transformations included a modified
      Luche reduction and a selective homoallylic alcohol epoxidation.

PMID- 28440077
TI  - Molecular Dynamics Simulations of the Standard Leonardite Humic Acid: Microscopic
      Analysis of the Structure and Dynamics.
AB  - Humic substances (HS) are abundant in the environment and play an important role
      in a number of biogeochemical processes including microbial activity, soil
      aggregation, plant growth, the retention and release of nutrients, the
      environmental fate of pollutants, and carbon storage. They are flexible,
      relatively small molecules forming supramolecular structures through weak
      interactions. Despite the great importance of understanding their behavior at the
      atomic level, computational modeling, a premier high-resolution technique
      providing great level of detail, has been surprisingly little-employed to study
      humic substances. Here, we use the recently developed Vienna Soil Organic-Matter
      Modeler to create representative models of a real HS sample, the standard
      Leonardite humic acid. Molecular dynamics simulations were used to probe the
      structure and dynamics of the system at a range of hydration levels. The studied
      systems were characterized in terms of their physicochemical properties,
      including density, dielectric properties, hydrogen bonding, etc. Moreover, the
      strength of sorption was estimated for three small organic compounds:
      benzaldehyde, propan-2-ol, and acetone. Strikingly, the HS models were validated
      against experimental data showing a remarkable agreement with calculated
      properties. Finally, we make the equilibrated models of the standard Leonardite
      humic acid, together with corresponding force-field parameters, available at the
      Vienna Soil Organic-Matter Modeler.

PMID- 28440079
TI  - Pressure-Induced Polymorphic, Optical, and Electronic Transitions of
      Formamidinium Lead Iodide Perovskite.
AB  - Formamidinium lead iodide (FAPbI3) perovskite as a superior solar cell material
      was investigated in two polymorphs at high pressures using in situ synchrotron X
      ray diffraction, FTIR spectroscopy, photoluminescence (PL) spectroscopy,
      electrical conductivity (EC) measurements, and ab initio calculations. We
      identified two new structures (i.e., Imm2 and Immm) for alpha-FAPbI3 but only a
      structural distortion (in C2/c) for delta-FAPbI3 upon compression. A pressure
      enhanced hydrogen bond plays a prominent role in structural modifications, as
      corroborated by FTIR spectroscopy. PL measurements and calculations consistently
      show the structure and pressure dependences of the band gap energies. Finally, EC
      measurements reveal drastically different transport properties of alpha- and
      delta-FAPbI3 at low pressures but a common trend to metallic states at high
      pressures. All of these observations suggest strongly contrasting structural
      stabilities and pressure-tuned optoelectric properties of the two FAPbI3
      polymorphs.

PMID- 28440080
TI  - Redox-Gated Tristable Molecular Brakes of Geared Rotation.
AB  - p-Bis(arylcarbonyl)pentiptycenes 2 (aryl = 4-(trifluoromethyl)phenyl) and 3 (aryl
      = mesityl) have been prepared and investigated as redox-gated molecular rotors.
      For 2, rotations about the pentiptycene-carbonyl bond (the alpha rotation) and
      about the aryl-carbonyl bond (the beta rotation) are independent, and the
      rotation barriers are 11.3 and 9.5 kcal mol-1, respectively, at 298 K. In
      contrast, the alpha and beta rotations in 3 are correlated (geared) in a 2-fold
      cogwheel pathway between the aryl and the pentiptycene groups with a much lower
      rotation barrier of 6.5 kcal mol-1 at 298 K in spite of the bulkier aryl groups.
      Electrochemical reduction of the neutral forms led first to radical anions (2*-
      and 3*-) and then to a bis(radical anion) for 22- but a dianion for 32-. The
      redox operations switch the independent alpha and beta rotations in 2 into a
      geared rotation in both 2*- and 22- and result in a slow-fast-stop rotation mode
      for 2-2*--22-. The two redox states 3*- and 32- retain the geared alpha and beta
      rotations and follow a fast-slow-stop mode for 3-3*--32-. Both molecular systems
      mimic tristable molecular brakes and display 8-9 orders of magnitude difference
      in rotation rate through the redox switching.

PMID- 28440081
TI  - Hydropyridylation of Olefins by Intramolecular Minisci Reaction.
AB  - An unprecedented cheap, mild and easy methodology for an intramolecular Minisci
      reaction based on a hydrogen atom transfer (HAT) initiated hydrofunctionalization
      of olefins was developed. The method is suitable for the construction of unusual
      dihydropyrano-pyridine and 1,2,3,4-tetrahydronaphthiridine structures and, unlike
      most similar reactions, does not require exclusion of air from the reaction
      medium.

PMID- 28440082
TI  - Metro Commuter Exposures to Particulate Air Pollution and PM2.5-Associated
      Elements in Three Canadian Cities: The Urban Transportation Exposure Study.
AB  - System-representative commuter air pollution exposure data were collected for the
      metro systems of Toronto, Montreal, and Vancouver, Canada. Pollutants measured
      included PM2.5 (PM = particulate matter), PM10, ultrafine particles, black
      carbon, and the elemental composition of PM2.5. Sampling over three weeks was
      conducted in summer and winter for each city and covered each system on a daily
      basis. Mixed-effect linear regression models were used to identify system
      features related to particulate exposures. Ambient levels of PM2.5 and its
      elemental components were compared to those of the metro in each city. A
      microenvironmental exposure model was used to estimate the contribution of a 70
      min metro commute to daily mean exposure to PM2.5 elemental and mass
      concentrations. Time spent in the metro was estimated to contribute the majority
      of daily exposure to several metallic elements of PM2.5 and 21.2%, 11.3% and
      11.5% of daily PM2.5 exposure in Toronto, Montreal, and Vancouver, respectively.
      Findings suggest that particle air pollutant levels in Canadian metros are
      substantially impacted by the systems themselves, are highly enriched in steel
      based elements, and can contribute a large portion of PM2.5 and its elemental
      components to a metro commuter's daily exposure.

PMID- 28440083
TI  - Systems Metabolomics for Prediction of Metabolic Syndrome.
AB  - The evolution of human health is a continuum of transitions, involving
      multifaceted processes at multiple levels, and there is an urgent need for
      integrative biomarkers that can characterize and predict progression toward
      disease development. The objective of this work was to perform a systems
      metabolomics approach to predict metabolic syndrome (MetS) development. A case
      control design was used within the French occupational GAZEL cohort (n = 112
      males: discovery study; n = 94: replication/validation study). Our integrative
      strategy was to combine untargeted metabolomics with clinical, sociodemographic,
      and food habit parameters to describe early phenotypes and build multidimensional
      predictive models. Different models were built from the discriminant variables,
      and prediction performances were optimized either when reducing the number of
      metabolites used or when keeping the associated signature. We illustrated that a
      selected reduced metabolic profile was able to reveal subtle phenotypic
      differences 5 years before MetS occurrence. Moreover, resulting metabolomic
      markers, when combined with clinical characteristics, allowed improving the
      disease development prediction. The validation study showed that this predictive
      performance was specific to the MetS component. This work also demonstrates the
      interest of such an approach to discover subphenotypes that will need further
      characterization to be able to shift to molecular reclassification and targeting
      of MetS.

PMID- 28440084
TI  - Prevalence and Co-Occurrence of Addictive Behaviors Among Russian and Spanish
      Youth.
AB  - : Recently, an addiction matrix measure was assessed among U.S. former
      alternative high school youth. This presentation seeks to examine the
      generalizability of findings using this measure among Russian and Spanish high
      school adolescents. Latent class analysis was used to explore addiction subgroups
      among adolescents in Russia (average age = 16.27; n = 715) and Spain (average age
      = 14.9; n = 811). Last 30-day prevalence of one or more of 11 addictions reviewed
      in the previous work was the primary focus (i.e., cigarettes, alcohol, hard
      drugs, eating, gambling, Internet, love, sex, exercise, work, and shopping) among
      Russian youth, and last-30 prevalence of one or more of 8 addictions among
      Spanish youth (the three drug use items had not been included in the
      questionnaire for these youths). Results confirmed a two-class model (addicted
      class and non-addicted class) among both Russian and Spanish adolescents. The
      mean number of addictions reported was 1.39 ( SD = 1.78) addictions among Russian
      youth and 1.56 ( SD = 1.68) addictions among Spanish youth. The prevalence of the
      sample that constituted the "addicted group" in Russia and Spain was 32.2% and
      28.6%, respectively. The most prevalent addictions (i.e., love, Internet,
      exercise) were similar. These results are similar to the findings previously
      reported for U.S. SAMPLE: Latent class structures for addictive behaviors are
      similar across international adolescent populations. Our results highlight the
      need to address multiple addictions in health education programming.

PMID- 28440085
TI  - Actinomycin D synergistically enhances the cytotoxicity of CDDP on KB cells by
      activating P53 via decreasing P53-MDM2 complex.
AB  - The aim of this study is to investigate the synergism of low dose of actinomycin
      D (LDActD) to the cytotoxicity of cisplatin (CDDP) on KB cells. The role of P53
      reactivation by LDActD in the synergism and its mechanism were further studied.
      Cell viability was determined by MTT assay. Apoptosis was determined by AnnexinV
      FITC/PI staining. Mitochondrial membrane potential (MMP) was detected by JC-1
      staining. Expression of proteins was detected by Western blotting (WB) and/or
      immunofluorescence (IF). Molecular docking of actinomycin D (ACTD) to Mouse
      double minute 2 homolog (MDM2) and Mouse double minute 2 homolog X (MDMX). MDMX
      was analyzed by Discovery Studio. The content of P53-MDM2 complex was detected by
      ELISA assay. The cytotoxicity of CDDP was increased by the combination of LDActD
      in kinds of cancer cells. Molecular docking showed strong interaction between
      ACTD and MDM2/MDMX. Meanwhile, LDActD significantly decreased P53-MDM2 complex.
      Significant increase of the apoptotic activity by the combination therapy in KB
      cells is P53 upregulated modulator of apoptosis (PUMA) dependent. In addition to
      the decrease in MMP, LDActD increased P53 regulated protein and decreased BCL-XL
      in KB cells. LDActD efficiently enhanced the cytotoxicity of CDDP in cancer cells
      and induced P53-PUMA-dependent and mitochondria-mediated apoptosis in KB cells.
      The reactivation of P53 was probably achieved by disturbing the interaction of
      P53 and MDM2/MDMX.

PMID- 28440086
TI  - DEBIRI plus capecitabine: a treatment option for refractory liver-dominant
      metastases from colorectal cancer.
AB  - AIM: This single institution Phase II study evaluated drug-eluting beads loaded
      with irinotecan (DEBIRI) plus capecitabine in pretreated patients with colorectal
      cancer liver metastases. PATIENTS & METHODS: Forty patients with liver-limited or
      liver-dominant disease, who have failed at least two previous lines of
      chemotherapy, underwent either four DEBIRI at 2-week interval or two DEBIRI every
      4 weeks for bilobar or single-lobe metastases, respectively. Capecitabine was
      given at 1000 mg/m2 twice daily on days 1-14 every 3 weeks. RESULTS: Seven
      partial responses and 12 stable diseases were observed, achieving a disease
      control rate of 47.5%. Median progression-free survival and overall survival
      resulted 4 and 8 months, respectively. Grade 3 adverse events occurred in 6/40
      points (15%) of patients. CONCLUSION: DEBIRI plus capecitabine is a valid
      treatment option for heavily pretreated patients with colorectal cancer liver
      metastases.

PMID- 28440087
TI  - Cervical dural calcification and cervical myelopathy in X-linked
      hypophosphataemic rickets: a case report and review of the literature.
AB  - X-linked hypophosphataemic rickets (XLHR) is a genetic disorder resulting from a
      genetic mutation in the PHEX gene. This may cause ossification of soft tissue
      structures risking spinal cord compression. We present the first known case of
      cervical dural calcification secondary to XLHR to cause myelopathic symptoms due
      to cord compression.

PMID- 28440089
TI  - Corrigendum.

PMID- 28440088
TI  - Head and neck giant cell arteritis: an autoimmune disease with many faces.
AB  - CONCLUSION: A high rate of infrequent presentations of giant cell arteritis were
      seen in the ENT department and should be anticipated as a differential diagnosis
      in every older patient with odynophagia with high CRP values without cause in
      thorough ENT examination. OBJECTIVE: To describe the clinical manifestation of
      head and neck giant cell arteritis and to derive a diagnostic pathway covering
      atypical cases. METHOD: Single-center, retrospective analysis of cases with GCA
      in the head and neck region (HN-GCA) (2002-2012) to describe the clinical
      presentation and to derive a diagnostic pathway covering manifestations
      presenting to an ENT department. RESULTS: Sixty-five patients were newly
      diagnosed with HN-GCA in the department of otolaryngology, ophthalmology and
      neurology. The most frequent symptoms were loss of vision (83%) and new onset
      headache (63%). Eight patients (12%) presented with infrequent manifestations,
      predominantly in the department of otorhinolaryngology. The most common atypical
      presentation (50%) was odynophagia in conjunction with high CRP values misleading
      to an infectious cause and delaying diagnosis. A diagnostic pathway for GCA was
      derived based on the ACR classification criteria and the clinical findings.

PMID- 28440090
TI  - Spermatocytic Tumor With Sarcoma: A Rare Testicular Neoplasm.
AB  - Spermatocytic tumor, formerly known as spermatocytic seminoma, is an uncommon
      testicular neoplasm which is a distinct clinicopathologic entity from classic
      seminoma. These tumors are not associated with germ cell neoplasia in situ, other
      germ cell tumors, or isochromosome 12p. Although typically, these tumors have an
      excellent prognosis occasional cases are associated with sarcoma and have a very
      poor prognosis. We present a case of spermatocytic tumor with sarcoma showing a
      chondrosarcomatous component, discuss the pathologic findings and differential
      diagnosis and provide follow-up information.

PMID- 28440091
TI  - Microbial exopolysaccharide-mediated synthesis and stabilization of metal
      nanoparticles.
AB  - Exopolysaccharides (EPSs) are structurally and functionally valuable biopolymer
      secreted by different prokaryotic and eukaryotic microorganisms in response to
      biotic/abiotic stresses and to survive in extreme environments. Microbial EPSs
      are fascinating in various industrial sectors due to their excellent material
      properties and less toxic, highly biodegradable, and biocompatible nature.
      Recently, microbial EPSs have been used as a potential template for the rapid
      synthesis of metallic nanoparticles and EPS-mediated metal reduction processes
      are emerging as simple, harmless, and environmentally benign green chemistry
      approaches. EPS-mediated synthesis of metal nanoparticles is a distinctive
      metabolism-independent bio-reduction process due to the formation of interfaces
      between metal cations and the polyanionic functional groups (i.e. hydroxyl,
      carboxyl and amino groups) of the EPS. In addition, the range of physicochemical
      features which facilitates the EPS as an efficient stabilizing or capping agents
      to protect the primary structure of the metal nanoparticles with an encapsulation
      film in order to separate the nanoparticle core from the mixture of composites.
      The EPS-capping also enables the further modification of metal nanoparticles with
      expected material properties for multifarious applications. The present review
      discusses the microbial EPS-mediated green synthesis/stabilization of metal
      nanoparticles, possible mechanisms involved in EPS-mediated metal reduction, and
      application prospects of EPS-based metal nanoparticles.

PMID- 28440092
TI  - Comparison of maternal omentin-1 levels and genetic variability between
      spontaneous term and preterm births.
AB  - OBJECTIVE: To determine maternal omentin-1 levels and genetic variability in the
      omentin-1 gene in women with spontaneous term and preterm births (PTBs).
      MATERIALS AND METHODS: Maternal serum omentin-1 levels and the role of the
      omentin-1 Val109Asp (rs2274907) polymorphism were evaluated in 32 women with
      spontaneous term birth (sTB) and 30 women with spontaneous preterm birth (sPTB)
      including women with (n = 16) and without (n = 14) preterm premature rupture of
      membranes (PPROM). RESULTS: Maternal omentin-1 levels were significantly lower in
      women with sPTBs compared to term births during the hospitalization period (p =
      .015). However, maternal omentin-1 levels were similar in women with sPTBs with
      and without PPROM (p = .990). Furthermore, the omentin-1 Val109Asp polymorphism
      was found to have no significant effect on omentin-1 serum levels. In addition,
      no significant differences in genotype distributions and allelic frequencies
      between sTB and sPTB were established. CONCLUSIONS: High omentin-1 levels in
      normal sTBs compared to PTBs without significant differences between cases with
      and without PPROM suggest that omentin-1 plays a potential role in the
      pathophysiology of PTB but not in the PPROM mechanism itself.

PMID- 28440093
TI  - Turmeric (Curcuma longa L.) extract may prevent the deterioration of spatial
      memory and the deficit of estimated total number of hippocampal pyramidal cells
      of trimethyltin-exposed rats.
AB  - CONTEXT: Protection of neurons from degeneration is an important preventive
      strategy for dementia. Much of the dementia pathology implicates oxidative stress
      pathways. Turmeric (Curcuma longa L.) contains curcuminoids which has anti
      oxidative and neuro-protective effects. These effects are considered to be
      similar to those of citicoline which has been regularly used as one of standard
      medications for dementia. OBJECTIVE: This study aimed at investigating the
      effects of turmeric rhizome extract on the hippocampus of trimethyltin (TMT)
      treated Sprague-Dawley rats. MATERIALS AND METHODS: The rats were divided
      randomly into six groups, i.e., a normal control group (N); Sn group, which was
      given TMT chloride; Sn-Cit group, which was treated with citicoline and TMT
      chloride; and three Sn-TE groups, which were treated with three different dosages
      of turmeric rhizome extract and TMT chloride. Morris water maze test was carried
      out to examine the spatial memory. The estimated total number of CA1 and CA2-CA3
      pyramidal cells was calculated using a stereological method. RESULTS: The
      administration of turmeric extract at a dose of 200 mg/kg bw has been shown to
      prevent the deficits in the spatial memory performance and partially inhibit the
      reduction of the number of CA2-CA3 regions pyramidal neurons. DISCUSSION: TMT
      induced neurotoxic damage seemed to be mediated by the generation of reactive
      oxygen species and reactive nitrogen species. Turmeric extract might act as anti
      inflammatory as well as anti-oxidant agent. CONCLUSIONS: The effects of turmeric
      extract at a dose of 200 mg/kg bw seem to be comparable to those of citicoline.

PMID- 28440094
TI  - Small group activities within academic communities improve the connectedness of
      students and faculty.
AB  - BACKGROUND: The University of California, San Diego, School of Medicine
      implemented a curriculum change that included reduction of lectures,
      incorporation of problem-based learning and other small group activities. Six
      academic communities were introduced for teaching longitudinal curricular content
      and organizing extracurricular activities. METHODS: Surveys were collected from
      904 first- and second-year medical students over 6 years. Student satisfaction
      data with their sense of connectedness and community support were collected
      before and after the implementation of the new curriculum. In a follow-up survey,
      medical students rated factors that contributed to their sense of connectedness
      with faculty and students (n = 134). RESULTS: Students' perception of
      connectedness to faculty significantly increased following implementation of a
      curriculum change that included academic communities. Students ranked small group
      clinical skills activities within academic communities significantly higher than
      other activities concerning their sense of connectedness with faculty. Students'
      perception of connectedness among each other was high at baseline and did not
      significantly change. Small group activities scored higher than extracurricular
      activities regarding students' connectedness among themselves. CONCLUSIONS: The
      implementation of a new curriculum with more small group educational activities
      including academic communities enhanced connectedness between students and
      faculty and resulted in an increased sense of community.

PMID- 28440095
TI  - What does the literature say about using robots on children with disabilities?
AB  - PURPOSE: The purpose of this study is to examine the extent and type of robots
      used for the rehabilitation and education of children and young people with CP
      and ASD and the associated outcomes. METHODS: The scholarly literature was
      systematically searched and analyzed. Articles were included if they reported the
      results of robots used or intended to be used for the rehabilitation and
      education of children and young people with CP and ASD during play and educative
      and social interaction activities. RESULTS: We found 15 robotic systems reported
      in 34 studies that provided a low level of evidence. The outcomes were mainly for
      children with ASD interaction and who had a reduction in autistic behaviour, and
      for CP cognitive development, learning, and play. CONCLUSION: More research is
      needed in this area using designs that provide higher validity. A centred design
      approach is needed for developing new low-cost robots for this population.
      Implications for rehabilitation In spite of the potential of robots to promote
      development in children with ASD and CP, the limited available evidence requires
      researchers to conduct studies with higher validity. The low level of evidence
      plus the need for specialized technical support should be considered critical
      factors before making the decision to purchase robots for use in treatment for
      children with CP and ASD. A user-entered design approach would increase the
      chances of success for robots to improve functional, learning, and educative
      outcomes in children with ASD and CP. We recommend that developers use this
      approach. The participation of interdisciplinary teams in the design,
      development, and implementation of new robotic systems is of extra value. We
      recommend the design and development of low-cost robotic systems to make robots
      more affordable.

PMID- 28440097
TI  - Exploring the role of classroom-based learning in professional identity formation
      of family practice residents using the experiences, trajectories, and
      reifications framework.
AB  - BACKGROUND: Classroom-based learning such as academic half day has undervalued
      social aspects. We sought to explore its role in the professional identity
      development of family medicine residents. METHODS: In this case study, residents
      and faculty from four training sites in the University of British Columbia
      Department of Family Practice were interviewed. The "experiences, trajectories,
      and reifications (ETR) framework" was used as a sensitizing tool for modified
      inductive (thematic) analysis of the transcripts. RESULTS: Classroom-based
      learning provided a different context for residents' interpretation of their
      clinical experiences, characterized as a "home base" for rotating urban
      residents, and a connection to a larger academic community for residents in rural
      training sites. Both these aspects were important in creating a positive
      trajectory of professional identity formation. Teaching directed at the learning
      needs of family physicians, and participation of family practice faculty as
      teachers and role models was a precipitation of a curriculum "centered in family
      medicine." Interactions between family medicine residents and faculty in the
      classroom facilitated the necessary engagements to reify a shared understanding
      of the discipline of family practice. CONCLUSIONS: Classroom-based learning has
      substantial impact on professional identity formation at an individual and
      collective level.

PMID- 28440098
TI  - Early diagnosis of amyotrophic lateral sclerosis mimic syndromes: pros and cons
      of current clinical diagnostic criteria.
AB  - OBJECTIVE: To describe the frequency and clinical characteristics of patients
      referred to a tertiary neuromuscular clinic as having amyotrophic lateral
      sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to
      identify the reasons that led to the revision of the diagnosis. METHODS: We
      reviewed the final diagnosis of all patients prospectively registered in the Sant
      Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical
      evaluation and a clinically-guided electrophysiological study were performed at
      first evaluation. RESULTS: Twenty of 314 (6.4%) patients included were re
      diagnosed as having a condition other than ALS, in 18 cases already at first
      evaluation. An alternative specific diagnosis was identified in 17 of those 20,
      consisting of a wide range of conditions. The main finding leading to an
      alternative diagnosis was the result of the electrophysiological study. Fifty per
      cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most
      common clinical phenotype at onset in patients with ALS mimic syndromes was
      progressive muscular atrophy (PMA). CONCLUSIONS: Misdiagnosing ALS is still a
      common problem. Early identification of ALS mimic syndromes is possible based on
      atypical clinical features and a clinically-guided electrophysiological study.
      Patients should be attended in specialised centres. The application of EECr helps
      to identify ALS misdiagnoses.

PMID- 28440096
TI  - Strategies in Ebola virus disease (EVD) diagnostics at the point of care.
AB  - Ebola virus disease (EVD) is a devastating, highly infectious illness with a high
      mortality rate. The disease is endemic to regions of Central and West Africa,
      where there is limited laboratory infrastructure and trained staff. The recent
      2014 West African EVD outbreak has been unprecedented in case numbers and
      fatalities, and has proven that such regional outbreaks can become a potential
      threat to global public health, as it became the source for the subsequent
      transmission events in Spain and the USA. The urgent need for rapid and
      affordable means of detecting Ebola is crucial to control the spread of EVD and
      prevent devastating fatalities. Current diagnostic techniques include molecular
      diagnostics and other serological and antigen detection assays; which can be time
      consuming, laboratory-based, often require trained personnel and specialized
      equipment. In this review, we discuss the various Ebola detection techniques
      currently in use, and highlight the potential future directions pertinent to the
      development and adoption of novel point-of-care diagnostic tools. Finally, a case
      is made for the need to develop novel microfluidic technologies and versatile
      rapid detection platforms for early detection of EVD.

PMID- 28440099
TI  - Antibiotic susceptibility of Helicobacter pylori in Iceland.
AB  - BACKGROUND: Increasing resistance of Helicobacter pylori (H. pylori) to
      antibiotics calls for constant re-evaluation of multidrug regimens that have been
      used to eradicate the infection. The aim of this study was to evaluate the
      current antibiotic susceptibility of H. pylori in an Icelandic cohort. METHODS:
      Patients referred for gastroscopy were recruited prospectively. Those found to
      have a positive rapid urease test were included in the study. Susceptibility
      testing was conducted by the Epsilometer test (E-test) method for ampicillin,
      clarithromycin, levofloxacin, metronidazole and tetracycline. Results were
      obtained after three days of incubation in microaerophilic conditions at 37 
      degrees C, except for the metronidazole were the first 24 hours were anaerobic.
      RESULTS: Of the 613 patients who underwent gastroscopy, 138 (23%) had a positive
      rapid urease test. H. pylori was successfully cultured from 105 (76%) of the
      urease test positive patients and the isolates were tested for antibiotic
      susceptibility. Five patients had prior H. pylori eradication. Antibiotic
      resistance for ampicillin, clarithromycin, levofloxacin, metronidazole and
      tetracycline was 0%, 9%, 4%, 1% and 0%, respectively. If those who had previously
      undergone eradication treatment were excluded, the resistance was 0%, 6%, 3%, 1%
      and 0%, respectively. Clarithromycin resistance was higher amongst women than
      men, 13% vs. 5%, however, not significantly. Clarithromycin resistance was 60%
      amongst those who had previously received eradication treatment compared to 6% of
      those who had not (p < .0001). CONCLUSIONS: Clarithromycin resistance amongst the
      H. pylori isolates can be considered relatively low. Therefore, in the current
      cohort, standard triple-drug clarithromycin-containing regimen should remain the
      first-line treatment against H. pylori.

PMID- 28440100
TI  - Detrimental effects of nicotine on thioacetamide-induced liver injury in mice.
AB  - AIM: Nicotine exerts a number of physiological effects. The purpose of this study
      was to determine the effects of nicotine on thioacetamide (TAA)-induced liver
      fibrosis in mice. MATERIALS AND METHODS: For in vivo experiments, hepatic
      fibrosis was induced by TAA (0.25 g/kg, i.p.) three times a week for 6 weeks.
      Mice of TAA treated groups were administered daily with distilled water and
      nicotine (50 or 100 MUg/mL) via gastrogavage throughout the experimental period.
      For in vitro experiments, HepG2 (human liver cancer cell line) and LX-2 (human
      hepatic stellate cell line) were used to determine oxidative stress and fibrosis,
      respectively. RESULTS: Compared to control groups, TAA treated groups had
      significantly differences in serum alanine transferase and aspartate
      aminotransferase levels and nicotine accentuated liver injury. Moreover, nicotine
      increased the mRNA levels of TAA-induced transforming growth factor-beta (TGF
      beta) and collagen type I alpha 1 in the liver. Nicotine also increased TAA
      induced oxidative stress. Histological examination confirmed that nicotine
      aggravated the degree of fibrosis caused by TAA treatment. Additionally, nicotine
      enhanced hepatic stellate cell activation via promoting the expression of alpha
      smooth muscle actin. CONCLUSIONS: Oral administration of nicotine significantly
      aggravated TAA-induced hepatic fibrosis in mice through enhancing TGF-beta
      secretion and TAA-induced oxidative stress. The increase in TGF-beta levels might
      be associated with the strengthening of oxidative processes, subsequently leading
      to increased hepatic stellate cell activation and extracellular matrix
      deposition. These results suggest that patients with liver disease should be
      advised to abandon smoking since nicotine may exacerbate hepatic fibrosis.

PMID- 28440102
TI  - Smoking addiction: the shift from head to hands: Approach bias towards smoking
      related cues in low-dependent versus dependent smokers.
AB  - The dual process theory is central to several models of addiction, implying both
      an increase of stimulus salience and deficits in inhibitory control. Our major
      aim is to provide behavioral evidence for an approach bias tendency in smokers
      and more specifically during smoking cue exposure. The second aim is to examine
      whether this bias differs in low-dependent versus dependent smokers. Thirty-two
      smokers (17 low dependent and 15 dependent; cut-off FTND of 4) and 28 non-smokers
      performed a modified Go/NoGo task using tobacco-related words and neutral words
      as stimuli. Smokers generally made more mistakes and tended to be faster for
      smoking-related cues specifically. Low dependents acknowledged more their
      dependency in declarative questionnaires while making more errors and being
      slower specifically on smoking cues; dependent smokers were less prone to
      indicate their addiction, but were faster and accurate when it came to picking
      the smoking cues. These results suggest that a shift has operated from a mental
      preoccupation with smoking in the low-dependent group, to smoking as a motor
      habit in our dependent group. This finding invites experts to rethink smoking
      addiction in the light of this crucial moment, namely, the shift "from head to
      hands".

PMID- 28440101
TI  - Behind the scenes in urinalysis: to report or not to report.

PMID- 28440103
TI  - British Association for Psychopharmacology consensus guidance on the use of
      psychotropic medication preconception, in pregnancy and postpartum 2017.
AB  - Decisions about the use of psychotropic medication in pregnancy are an ongoing
      challenge for clinicians and women with mental health problems, owing to the
      uncertainties around risks of the illness itself to mother and fetus/infant,
      effectiveness of medications in pregnancy and risks to the fetus/infant from in
      utero exposure or via breast milk. These consensus guidelines aim to provide
      pragmatic advice regarding these issues. They are divided into sections on risks
      of untreated illness in pregnancy; general principles of using drugs in the
      perinatal period; benefits and harms associated with individual drugs; and
      recommendations for the management of specific disorders.

PMID- 28440104
TI  - The cut-off point for tympanic temperature as a heat strain index for evaluation
      of outdoor workers: a field study.
AB  - OBJECTIVES: The aims of this study were (a) to assess the agreement coefficient
      between tympanic temperatures and the most popular and valid heat stress index,
      wet bulb globe temperature (WBGT), in outdoor environments; (b) to determine a
      cut-off point for tympanic temperature as a heat strain index for evaluation of
      outdoor workers. METHODS: 1452 measurements of WBGT index and tympanic
      temperature were recorded for outdoor workers from nine different climatic
      regions. Consistency of the WBGT and tympanic temperature were tested. The cut
      off point for tympanic temperature in outdoor environments regarding WBGT
      evaluation was suggested based on obtained sensitivity and specificity from a
      receiver operating characteristic curve. RESULTS: The results showed that there
      were numerous situations in which WBGT exceeded the reference value, whilst the
      measured values of tympanic temperature rarely reached a permissible value for
      core temperature (38  degrees C). Therefore, appropriate consistency of results
      between the heat stress and strain indices was not achieved. CONCLUSION: The
      criterion of tympanic temperature equaling 37  degrees C was suggested as a cut
      off point for tympanic temperature as a heat strain index for outdoor environment
      evaluation.

PMID- 28440106
TI  - Identifying Early Markers of "Late Onset" Attention Deficit and
      Hyperactivity/Impulsivity Symptoms.
AB  - OBJECTIVE: In recent years, there has been an increased focus on "late onset"
      ADHD, referring to the onset of symptoms beyond childhood, into adolescence and
      adulthood. We aimed to identify childhood predictors of ADHD symptom increases
      over development. METHOD: We used growth mixture modeling to evaluate predictors
      of a "late onset" symptom trajectories in a longitudinal cohort study of youth
      measured at eight points from ages 7 to 15. RESULTS: Individuals with high levels
      of sensation seeking at age 7 were more likely to show a trajectory of ADHD
      symptoms characterized by increasing levels from age 7 than persistently low
      symptom levels. CONCLUSION: The late versus early onset distinction may align
      with the distinction between deficits in "bottom-up" versus "top-down" processes
      previously discussed in relation to ADHD. Results also raise the possibility that
      later onset symptoms could be predicted based on characteristics in childhood.

PMID- 28440105
TI  - Effect of doxazosin on stress reactivity and the ability to resist smoking.
AB  - Preclinical findings support a role for alpha1-adrenergic antagonists in reducing
      nicotine-motivated behaviors, but these findings have yet to be translated to
      humans. The current study evaluated whether doxazosin would attenuate stress
      precipitated smoking in the human laboratory. Using a well-validated laboratory
      analogue of smoking-lapse behavior, this pilot study evaluated whether doxazosin
      (4 and 8 mg/day) versus placebo attenuated the effect of stress (vs neutral
      imagery) on tobacco craving, the ability to resist smoking and subsequent ad
      libitum smoking in nicotine-deprived smokers ( n=35). Cortisol,
      adrenocorticotropin, norepinephrine, epinephrine, and physiologic reactivity were
      assessed. Doxazosin (4 and 8 mg/day vs placebo) decreased cigarettes per day
      during the 21-day titration period. Following titration, doxazosin (4 and 8
      mg/day vs placebo) decreased tobacco craving. During the laboratory session,
      doxazosin (8 mg/day vs placebo) further decreased tobacco craving following
      stress versus neutral imagery. Doxazosin increased the latency to start smoking
      following stress, and reduced the number of cigarettes smoked. Dosage of 8 mg/day
      doxazosin increased or normalized cortisol levels following stress imagery and
      decreased cortisol levels following neutral imagery. These preliminary findings
      support a role for the noradrenergic system in stress-precipitated smoking
      behavior, and support further development of doxazosin as a novel
      pharmacotherapeutic treatment strategy for smoking cessation.

PMID- 28440108
TI  - Microbiology of the Upper and Lower Airways in Pediatric Cystic Fibrosis
      Patients.
AB  - Objective To evaluate the microbiology of the upper and lower airways in
      pediatric cystic fibrosis (CF) patients who underwent sinus surgery. Study Design
      Retrospective case series with chart review. Setting Tertiary care children's
      hospital. Subjects and Methods A total of 201 paired sinus and pulmonary cultures
      from 105 CF patients were identified between 1996 and 2014. Demographics and
      culture results were analyzed. Results The mean age of patients was 11.2 +/- 5.4
      years (range, 1-27 years), and approximately one-half were female. Methicillin
      sensitive Staphylococcus aureus was the most common pathogen overall. A
      significantly higher prevalence of Pseudomonas aeruginosa (32% for pulmonary and
      37% for sinus cultures) was observed in older patients versus younger patients (
      P < .001). There was low to moderate agreement between sinus and pulmonary
      cultures (Kappa statistic range, 0.03-0.56). The prevalence of methicillin
      resistant S aureus (MRSA) increased significantly for lower respiratory tract
      culture (from 5% to 16%) and sinus culture (from 5% to 27%) between 1996-2004 and
      2010-2014 ( P = .016 and P < .001, respectively). The prevalence of positive
      sinus cultures increased from 40% to 85% between 1996-2004 and 2010-2014 ( P =
      .018). Patients with pulmonary MRSA were more likely to be coinfected with
      pulmonary P aeruginosa (risk ratio, 2.4; 95% CI, 1.2-4.8; P = .015) or
      Aspergillus fumigatus (risk ratio, 2.2; 95% CI, 1.2-4.8; P = .035). Conclusions
      There is low to moderate correlation between pulmonary and sinus pathogens in CF
      patients. This is important to consider when treating infections. The prevalence
      of MRSA in sinus cultures has increased over time and warrants further
      investigation.

PMID- 28440110
TI  - In-parallel connected intermittent hemodialysis through ECMO does not affect
      hemodynamic parameters derived from transpulmonary thermodilution.
AB  - INTRODUCTION: We report a case of renal replacement therapy (RRT) during
      extracorporeal membrane oxygenation (ECMO) via a single venous access and analyze
      the feasibility of transpulmonary thermodilution (TPTD) for hemodynamic
      monitoring. CASE REPORT: ECMO and RRT connected into the ECMO-extracorporeal
      circuit were performed via a single venous access because of multiple venous
      thromboses. An indicator for TPTD and pulse contour analysis (PCA) was applied
      into the central venous catheter (CVC) placed in the right vena jugularis. TPTD
      and PCA demonstrated comparable cardiac index. DISCUSSION: Congruent data for
      TPTD and PCA could be observed during TPTD and PCA measurements before ECMO,
      after ECMO and during ECMO and RRT. This might be explained by high blood flow
      having the lowest impact on TPTD by venous drainage in the femoral vein/distal
      vena cava and the TPTD indicator injection using the jugular CVC, as reported in
      our case. CONCLUSION: Hemodynamic monitoring using TPTD and PCA during ECMO/RRT
      is feasible and provides reliable results.

PMID- 28440109
TI  - The demography of words: The global decline in non-numeric fertility preferences,
      1993-2011.
AB  - This paper examines the decline in non-numeric responses to questions about
      fertility preferences among women in the developing world. These types of
      response-such as 'don't know' or 'it's up to God'-have often been interpreted
      through the lens of fertility transition theory as an indication that
      reproduction has not yet entered women's 'calculus of conscious choice'. However,
      this has yet to be investigated cross-nationally and over time. Using 19 years of
      data from 32 countries, we find that non-numeric fertility preferences decline
      most substantially in the early stages of a country's fertility transition. Using
      country-specific and multilevel models, we explore the individual- and contextual
      level characteristics associated with women's likelihood of providing a non
      numeric response to questions about their fertility preferences. Non-numeric
      fertility preferences are influenced by a host of social factors, with
      educational attainment and knowledge of contraception being the most robust and
      consistent predictors.

PMID- 28440111
TI  - Quality of Life Outcomes in a Pediatric Thalassemia Population in Egypt.
AB  - Thalassemia is a disorder of hemoglobin (Hb) synthesis characterized by chronic
      hemolysis. In beta-thalassemias major (beta-TM), patients require regular
      transfusion at an early age due to severe anemia. Subsequently, intensive
      chelation therapy is initiated to mitigate the effects of the resultant iron
      overload. Clinical disease burden and the demanding treatment can affect health
      related quality of life (HRQoL) outcomes in this population. The aim of this
      study was to assess HRQoL outcomes in Egyptian pediatric thalassemia patients.
      Patients were enrolled simultaneously from the hematology clinic at the National
      Research Institute in Cairo, Egypt. The Arabic version of SF36 tool was used to
      assess HRQoL outcomes. Socioeconomic data were collected by patient and parent
      interviews. Clinical data were collected by review of medical records. One
      hundred and thirty patients and 60 controls were enrolled, with a mean age of 5.4
      +/- 3.2 years and 6.3 +/- 3.0, respectively. The HRQoL outcome scores were lower
      in all domains in the thalassemia group compared to the control group (p =
      0.0001). Transfusion-dependent (TD) patients had lower HRQoL scores compared to
      nontransfusion-dependent (NTD) patients (p = 0.0001). Patient education and
      maternal education were independently associated with better HRQoL scores (p =
      0.007, p = 0.028, respectively). Residents of rural areas reported lower scores
      compared to urban residents (p = 0.026). Thalassemia was associated with lower
      HRQoL scores, in all domains, compared to HRQoL in unaffected controls. Chronic
      transfusion independence, patient education, and maternal education were all
      associated with higher HRQoL scores. Psychological, social, and economic support
      for families with thalassemia are all essential tools to improve HRQoL outcomes.

PMID- 28440112
TI  - Patient-specific prediction of functional recovery after stroke.
AB  - Background and aims Clinical predictive models for stroke recovery could offer
      the opportunity of targeted early intervention and more specific information for
      patients and carers. In this study, we developed and validated a patient-specific
      prognostic model for monitoring recovery after stroke and assessed its clinical
      utility. Methods Four hundred and ninety-five patients from the population-based
      South London Stroke Register were included in a substudy between 2002 and 2004.
      Activities of daily living were assessed using Barthel Index) at one, two, three,
      four, six, eight, 12, 26, and 52 weeks after stroke. Penalized linear mixed
      models were developed to predict patients' functional recovery trajectories. An
      external validation cohort included 1049 newly registered stroke patients between
      2005 and 2011. Prediction errors on discrimination and calibration were assessed.
      The potential clinical utility was evaluated using prognostic accuracy
      measurements and decision curve analysis. Results Predictive recovery curves
      showed good accuracy, with root mean squared deviation of 3 Barthel Index points
      and a R2 of 83% up to one year after stroke in the external cohort. The negative
      predictive values of the risk of poor recovery (Barthel Index <8) at three and 12
      months were also excellent, 96% (95% CI [93.6-97.4]) and 93% [90.8-95.3],
      respectively, with a potential clinical utility measured by likelihood ratios
      (LR+:17 [10.8-26.8] at three months and LR+:11 [6.5-17.2] at 12 months). Decision
      curve analysis showed an increased clinical benefit, particularly at threshold
      probabilities of above 5% for predictive risk of poor outcomes. Conclusions A
      recovery curves tool seems to accurately predict progression of functional
      recovery in poststroke patients.

PMID- 28440114
TI  - Commentary: Preoperative Aortic Morphology Identifies Patients at High Risk for
      Late Failure of Endovascular Aneurysm Repair.

PMID- 28440113
TI  - Major Limb Outcomes Following Lower Extremity Endovascular Revascularization in
      Patients With and Without Diabetes Mellitus.
AB  - PURPOSE: To determine whether diabetes mellitus has an independent impact on
      major limb outcomes at 1 year after endovascular treatment of lower extremity
      peripheral artery disease (PAD). METHODS: The study involved 1906 consecutive
      patients (mean age 66 years; 1469 men) enrolled in the observational Excellence
      in Peripheral Artery Disease (XLPAD) registry ( ClinicalTrials.gov identifier
      NCT01904851) between January 2005 and October 2015 after undergoing index
      endovascular procedures in 2426 limbs for arterial occlusive disease. Patient
      outcomes included 12-month target limb amputation (above ankle) and target limb
      revascularization as well as all-cause death. Kaplan-Meier analysis and adjusted
      Cox proportional hazard models were used for time-to-event analysis of outcomes
      for the entire study sample as well as for the critical limb ischemia (CLI) and
      claudication subgroups. Results of the Cox regression models are reported as the
      hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Diabetics undergoing
      endovascular procedures had higher rates of comorbid conditions (p<0.001), CLI
      (p<0.001), heavily calcified lesions (p=0.002), multivessel disease (p=0.030),
      and fewer infrapopliteal runoff vessels (p<0.001). Regression analysis after
      adjusting for confounders revealed significantly higher target limb major
      amputation in diabetics compared with nondiabetics (HR 5.02, 95% CI 1.44 to
      17.56, p=0.011). However, repeat revascularization rates were similar. When
      considering CLI and claudication subgroups, diabetes was associated with a
      nonsignificant increased risk of 12-month major amputation only for patients
      presenting with CLI (HR 3.48, 95% CI 0.97 to 12.51, p=0.056). Diabetes was also
      associated with an increased risk of 12-month all-cause mortality in the overall
      study sample (HR 4.64, 95% CI 2.01 to 10.70, p<0.001) and in the CLI subgroup (HR
      14.15, 95% CI 3.16 to 63.32, p<0.001) but not in the claudication subgroup (HR
      1.42, 95% CI 0.45 to 4.54, p=0.552). CONCLUSION: Diabetes increases the risk of
      major amputation and all-cause death at 12 months following endovascular
      revascularization in patients with symptomatic PAD. These risks are especially
      heightened in patients presenting with CLI.

PMID- 28440116
TI  - Telemedical strategies for the improvement of secondary prevention in patients
      with cerebrovascular events-A systematic review and meta-analysis.
AB  - Background Data from European countries consistently show that guideline-conform
      secondary prevention after stroke/transient ischemic attack is being realized in
      only 50-80% of patients. Use of telemedicine to support long-term secondary
      prevention has been effective in other cardiovascular diseases. Aims We reviewed
      current evidence for telemedical-supported strategies for the improvement of
      secondary prevention after stroke/transient ischemic attack. A systematic review
      was performed in accordance with the PRISMA statement searching MEDLINE, the
      Cochrane Central Register of Controlled Trials, and reference lists of articles
      published until 18 May 2016. Randomized controlled trials and observational
      studies were included if they analyzed the effect of a telemedical strategy for
      supporting secondary prevention after stroke/transient ischemic attack compared
      to usual care and reported primary (behavior according to guidelines, e.g.,
      medication adherence) or surrogate outcomes (consequences of primary outcome,
      e.g., blood pressure). Summary of review The review included 13 of 100 identified
      studies involving 2672 patients. Telemedical support mainly comprised telephone
      interventions, predominantly done by nurses. Outcomes were heterogeneous:
      medication adherence did not differ in one randomized controlled trial (p =
      0.089). Mortality was reported in one study and was significantly (p < 0.001)
      higher in patients non-participating in a web-based intervention. Four studies
      assessed blood pressure in a comparable way that allowed calculation of a meta
      analysis. In that, telemedical intervention had a significant blood-pressure
      lowering effect compared to the control group (mean difference -6.14 (95%
      confidence interval -10.41, -1.87), p = 0.005). Conclusions Telemedical-supported
      secondary prevention in cerebrovascular diseases might be effective but larger
      trials with standardized interventions and outcome measures including clinical
      endpoints are needed.

PMID- 28440117
TI  - A nomogram to predict the probability of passing the American Board of Internal
      Medicine examination.
AB  - BACKGROUND: Although the American Board of Internal Medicine (ABIM) certification
      is valued as a reflection of physicians' experience, education, and expertise,
      limited methods exist to predict performance in the examination. PURPOSE: The
      objective of this study was to develop and validate a predictive tool based on
      variables common to all residency programs, regarding the probability of an
      internal medicine graduate passing the ABIM certification examination. METHODS:
      The development cohort was obtained from the files of the Cleveland Clinic
      internal medicine residents who began training between 2004 and 2008. A
      multivariable logistic regression model was built to predict the ABIM passing
      rate. The model was represented as a nomogram, which was internally validated
      with bootstrap resamples. The external validation was done retrospectively on a
      cohort of residents who graduated from two other independent internal medicine
      residency programs between 2007 and 2011. RESULTS: Of the 194 Cleveland Clinic
      graduates used for the nomogram development, 175 (90.2%) successfully passed the
      ABIM certification examination. The final nomogram included four predictors: In
      Training Examination (ITE) scores in postgraduate year (PGY) 1, 2, and 3, and the
      number of months of overnight calls in the last 6 months of residency. The
      nomogram achieved a concordance index (CI) of 0.98 after correcting for over
      fitting bias and allowed for the determination of an estimated probability of
      passing the ABIM exam. Of the 126 graduates from two other residency programs
      used for external validation, 116 (92.1%) passed the ABIM examination. The
      nomogram CI in the external validation cohort was 0.94, suggesting outstanding
      discrimination. CONCLUSIONS: A simple user-friendly predictive tool, based on
      readily available data, was developed to predict the probability of passing the
      ABIM exam for internal medicine residents. This may guide program directors'
      decision-making related to program curriculum and advice given to individual
      residents regarding board preparation.

PMID- 28440118
TI  - Direct short-term effects of EBP teaching: change in knowledge, not in attitude;
      a cross-cultural comparison among students from European and Asian medical
      schools.
AB  - INTRODUCTION: We report about the direct short-term effects of a Clinical
      Epidemiology and Evidence-based Medicine (CE-EBM) module on the knowledge,
      attitude, and behavior of students in the University Medical Center Utrecht
      (UMCU), Universitas Indonesia (UI), and University of Malaya (UM). METHODS: We
      used an adapted version of a 26-item validated questionnaire, including four
      subscales: knowledge, attitude, behavior, and future use of evidence-based
      practice (EBP). The four components were compared among the students in the three
      medical schools before the module using one-way ANOVA. At the end of the module,
      we measured only knowledge and attitudes. We computed Cronbach's alpha to assess
      the reliability of the responses in our population. To assess the change in
      knowledge and attitudes, we used the paired t-test in the comparison of scores
      before and after the module. RESULTS: In total, 526 students (224 UI, 202 UM, and
      100 UMCU) completed the questionnaires. In the three medical schools, Cronbach's
      alpha for the pre-module total score and the four subscale scores always exceeded
      0.62. UMCU students achieved the highest pre-module scores in all subscales
      compared to UI and UM with the comparison of average (SD) score as the following:
      knowledge 5.04 (0.4) vs. 4.73 (0.69) and 4.24 (0.74), p<0.001; attitude 4.52
      (0.64) vs. 3.85 (0.68) and 3.55 (0.63), p<0.001; behavior 2.62 (0.55) vs. 2.35
      (0.71) and 2.39 (0.92), p=0.016; and future use of EBP 4.32 (0.59) vs. 4.08
      (0.62) and 3.7 (0.71), p<0.01. The CE-EBM module increased the knowledge of the
      UMCU (from average 5.04+/-0.4 to 5.35+/-0.51; p<0.001) and UM students (from
      average 4.24+/-0.74 to 4.53+/-0.72; p<0.001) but not UI. The post-module scores
      for attitude did not change in the three medical schools. CONCLUSION: EBP
      teaching had direct short-term effects on knowledge, not on attitude. Differences
      in pre-module scores are most likely related to differences in the system and
      infrastructure of both medical schools and their curriculum.

PMID- 28440119
TI  - Improving recruitment into psychiatry: teaching strategies to enhance
      undergraduate interest.

PMID- 28440120
TI  - Characteristics of mentoring relationships formed by medical students and
      faculty.
AB  - BACKGROUND: Little is known about the characteristics of mentoring relationships
      formed between faculty and medical students. Individual mentoring relationships
      of clinical medical students at Munich Medical School were characterized
      quantitatively and qualitatively. METHODS: All students signing up for the
      mentoring program responded to a questionnaire on their expectations (n = 534).
      Mentees were asked to give feedback after each of their one-on-one meetings (n =
      203). A detailed analysis of the overall mentoring process and its
      characteristics was performed. For qualitative text analysis, free-text items
      were analyzed and categorized by two investigators. Quantitative analysis was
      performed using descriptive statistics and Wilcoxon-test to assess differences in
      grades between students with and without mentors. RESULTS: High-performing
      students were significantly more likely to participate in the mentoring program
      (p<0.001). Topics primarily discussed include the mentee's personal goals
      (65.5%), career planning (59.6%), and experiences abroad (57.6%). Mentees mostly
      perceived their mentors as counselors (88.9%), providers of ideas (85.0%), and
      role models (73.3%). Mentees emphasized the positive impact of the mentoring
      relationship on career planning (77.2%) and research (75.0%). CONCLUSIONS:
      Medical students with strong academic performance as defined by their grades are
      more likely to participate in formal mentoring programs. Mentoring relationships
      between faculty and medical students are perceived as a mutually satisfying and
      effective instrument for key issues in medical students' professional
      development. PRACTICAL IMPLICATIONS: Mentoring relationships are a highly
      effective means of enhancing the bidirectional flow of information between
      faculty and medical students. A mentoring program can thus establish a feedback
      loop enabling the educational institution to swiftly identify and address issues
      of medical students.

PMID- 28440121
TI  - Developing interprofessional health competencies in a virtual world.
AB  - BACKGROUND: Virtual worlds provide a promising means of delivering simulations
      for developing interprofessional health skills. However, developing and
      implementing a virtual world simulation is a challenging process, in part because
      of the novelty of virtual worlds as a simulation platform and also because of the
      degree of collaboration required among technical and subject experts. Thus, it
      can be difficult to ensure that the simulation is both technically satisfactory
      and educationally appropriate. METHODS: To address this challenge, we propose the
      use of de Freitas and Oliver's four-dimensional framework as a means of guiding
      the development process. We give an overview of the framework and describe how
      its principles can be applied to the development of virtual world simulations.
      RESULTS: We present two virtual world simulation pilot projects that adopted this
      approach, and describe our development experience in these projects. We directly
      connect this experience to the four-dimensional framework, thus validating the
      framework's applicability to the projects and to the context of virtual world
      simulations in general. CONCLUSIONS: We present a series of recommendations for
      developing virtual world simulations for interprofessional health education.
      These recommendations are based on the four-dimensional framework and are also
      informed by our experience with the pilot projects.

PMID- 28440122
TI  - Effects of low dose ionizing radiation on DNA damage-caused pathways by reverse
      phase protein array and Bayesian networks.
AB  - Ionizing radiation (IR) causing damages to Deoxyribonucleic acid (DNA)
      constitutes a broad range of base damage and double strand break, and thereby, it
      induces the operation of relevant signaling pathways such as DNA repair, cell
      cycle control, and cell apoptosis. The goal of this paper is to study how the
      exposure to low dose radiation affects the human body by observing the signaling
      pathway associated with Ataxia Telangiectasia mutated (ATM) using Reverse-Phase
      Protein Array (RPPA) and isogenic human Ataxia Telangiectasia (A-T) cells under
      different amounts and durations of IR exposure. In order to verify which proteins
      could be involved in a DNA damage-caused pathway, only proteins that highly
      interact with each other under IR are selected by using correlation coefficient.
      The pathway inference is derived from learning Bayesian networks in combination
      with prior knowledge such as Protein-Protein Interactions (PPIs) and signaling
      pathways from well-known databases. Learning Bayesian networks is based on a
      score and search scheme that provides the highest scored network structure given
      a score function, and the prior knowledge is included in the score function as a
      prior probability by using Dempster-Shafer theory (DST). In this way, the
      inferred network can be more likely to be similar to already discovered pathways
      and consistent with confirmed PPIs for more reliable inference. The experimental
      results show which proteins are involved in signaling pathways under IR, how the
      inferred pathways are different under low and high doses of IR, and how the
      selected proteins regulate each other in the inferred pathways. As our main
      contribution, overall results confirm that low dose IR could cause DNA damage and
      thereby induce and affect related signaling pathways such as apoptosis, cell
      cycle, and DNA repair.

PMID- 28440123
TI  - Delivering care to those in need: Improving palliative care using linked data.

PMID- 28440124
TI  - Perspectives on advance care planning among patients recently requiring non
      invasive ventilation for acute respiratory failure: A qualitative study using
      thematic analysis.
AB  - BACKGROUND: Patients requiring non-invasive ventilation for acute-on-chronic
      respiratory failure due to chronic obstructive pulmonary disease or heart failure
      exacerbations may have a poor prognosis underscoring the importance of advance
      care planning. AIM: We aimed to describe attitudes to, and experiences of,
      discussing the future among patients recently treated with non-invasive
      ventilation. DESIGN: Qualitative research using thematic analysis. SETTINGS AND
      PARTICIPANTS: Tertiary teaching hospital. Patients with acute hypercapnic
      respiratory failure requiring non-invasive ventilation. RESULTS: Individuals
      recently treated with non-invasive ventilation describe feeling the future is
      beyond their control and instead controlled by their illness. Participants often
      recognised their poor prognosis but avoided discussing some difficult topics. The
      majority preferred not to undergo cardiopulmonary resuscitation but most had not
      discussed this with healthcare professionals. When participants voiced concerns
      about their future health to family members, they were met with polarised
      responses. Some encountered willingness for further discussion, while others met
      deflection, deterring further conversation. An overarching narrative of 'Looking
      through my illness to an uncertain but concerning future' unites these themes.
      CONCLUSION: This study suggests opportunities and barriers for advance care
      planning in individuals with chronic disease. Patients' understanding of their
      prognosis and their attitudes to cardiopulmonary resuscitation suggests an
      opportunity for advance care planning. Structuring discussions around patients'
      preferences for care during future exacerbations may foster a sense of control
      over the future despite illness. The diversity of familial responses to patients'
      concerns about their future health has implications for advance care planning.
      These findings have the potential to improve care for patients with respiratory
      failure and suggest an important ongoing research agenda.

PMID- 28440125
TI  - Palliative care education for medical students: Differences in course evolution,
      organisation, evaluation and funding: A survey of all UK medical schools.
AB  - BACKGROUND: A proportion of newly qualified doctors report feeling unprepared to
      manage patients with palliative care and end-of-life needs. This may be related
      to barriers within their institution during undergraduate training. Information
      is limited regarding the current organisation of palliative care teaching across
      UK medical schools. AIMS: To investigate the evolution and structure of
      palliative care teaching at UK medical schools. DESIGN: Anonymised, web-based
      questionnaire. Settings/participants: Results were obtained from palliative care
      course organisers at all 30 UK medical schools. RESULTS: The palliative care
      course was established through active planning (13/30, 43%), ad hoc development
      (10, 33%) or combination of approaches (7, 23%). The place of palliative care
      teaching within the curriculum varied. A student-selected palliative care
      component was offered by 29/30 (97%). All medical schools sought student
      feedback. The course was reviewed in 26/30 (87%) but not in 4. Similarly, a
      course organiser was responsible for the palliative care programme in 26/30 but
      not in 4. A total of 22 respondents spent a mean of 3.9 h (median 2.5)/week in
      supporting/delivering palliative care education (<1-16 h). In all, 17/29 (59%)
      had attended a teaching course or shared duties with a colleague who had done so.
      Course organisers received titular recognition in 18/27 (67%; no title 9 (33%);
      unknown 3 (11%)). An academic department of Palliative Medicine existed in 12/30
      (40%) medical schools. Funding was not universally transparent. Palliative care
      teaching was associated with some form of funding in 20/30 (66%). CONCLUSION:
      Development, organisation, course evaluation and funding for palliative care
      teaching at UK medical schools are variable. This may have implications for
      delivery of effective palliative care education for medical students.

PMID- 28440126
TI  - Transcranial Doppler screening for stroke risk in children with sickle cell
      disease: a systematic review.
AB  - Background Sickle cell disease (SCD) is one of the most common causes of stroke
      in children worldwide. Based on the results of the Stroke Prevention Trial in
      Sickle Cell Anemia (STOP), annual transcranial Doppler ultrasound (TCD) screening
      for affected children is standard practice. However, the need for TCD
      surveillance programs could override the accuracy of the screening, affecting the
      correct stratification of stroke risk and subsequent clinical management of the
      target population. Aims To shed light on this issue, a systematic review of the
      literature on TCD screening for children and adolescents with SCD was carried out
      (CRD42016050549), according to a list of clinically relevant questions, with a
      particular focus on screening practices in European countries. Quality of the
      evidence was rated using the grading of recommendations assessment, development
      and evaluation. Summary of review Thirty-three studies published in English or
      French were included (5 randomized controlled trials, 8 experimental non
      randomized, and 20 observational studies). The quality of the retrieved evidence
      ranged between low and high, but was rated as moderate or high most of the times.
      TCD is effective as a screening tool for the primary prevention of stroke in SCD
      children. There is no high-quality evidence on the effectiveness of alternative
      screening methods, such as imaging-TCD with or without angle correction or
      magnetic resonance angiography. No evidence was found on effectiveness of the
      screening on children on hydroxyurea and with genotypes other than HbSS and
      HbS/beta0. No European data were found on screening rates or adherence of
      screening practices to the STOP protocol. Conclusions High-quality studies on
      alternative screening methods that are currently used in real-world practice, and
      on screening applicability to specific subgroups of patients are urgently needed.
      Considering the low awareness of the disease in European countries and the lack
      of data on screening practices and adherence, clinicians need up-to-date
      guidelines for more uniform and evidence-based surveillance of children with SCD.

PMID- 28440127
TI  - Assessment of the intraday variability of anthropometric measurements in the work
      environment: a pilot study.
AB  - Sitting for long periods of time, both during work and leisure times, is the
      typical behavior of the modern society. Especially at work, where there is not
      much flexibility, adopting the sitting posture for the entire day can cause some
      short-term and long-term effects. As workers' productivity and well-being relies
      on working conditions, evaluating the effects caused by work postures assumes a
      very important role. The purpose of this article was to evaluate the variation of
      some anthropometric measurements during one typical workday to understand whether
      the known long-term effects can also be seen and quantified in an 8-h period.
      Twenty participants were measured before and after work, using traditional
      anthropometry equipment. The data from the two repetitions were compared using
      statistical tests. The results showed a slight variation in the anthropometric
      measurements, some with a tendency to increase over time and others with a
      tendency to decrease.

PMID- 28440185
TI  - A Therapeutic Potential of Animal beta-hairpin Antimicrobial Peptides.
AB  - Endogenous antimicrobial peptides (AMPs) are evolutionary ancient molecular
      factors of innate immunity that play the key role in host defense. Because of the
      low resistance rate, AMPs have caught extensive attention as possible
      alternatives to conventional antibiotics. Over the last years, it has become
      evident that biological functions of AMPs are beyond direct killing of microbial
      cells. This review focuses on a relatively small family of animal host defense
      peptides with the beta-hairpin structure stabilized by disulfide bridges. Their
      small size, rigid structure, stability to proteases, and plethora of biological
      functions, including antibacterial, antifungal, antiviral, anticancer, endotoxin
      binding, metabolism- and immune- modulating activities, make natural beta-hairpin
      AMPs an attractive molecular basis for drug design.

PMID- 28440187
TI  - Genetic Modifications of Icosahedral Plant Virus-based Nanoparticles for Vaccine
      and Immunotherapy Applications.
AB  - Vaccine development is one of the greatest achievements of modern medicine.
      Vaccines made of live-attenuated pathogens can revert to virulent live strains,
      which causes safety concerns. On the other hand, the use of purified antigenic
      components as subunit vaccines is safer, but less effective, as these components
      induce lower levels of protective immunity. Multiple copy presentation of an
      antigenic determinant in a well-ordered and well-defined orientation on a
      nanosized particle can mimic the natural host-pathogen surface interaction to
      provide antigen stability and immunogenicity similar to that of conventional
      vaccines with improved safety. The icosahedral symmetry of plant viral capsid
      based nanoparticles is highly ordered and their multivalent structured protein
      nanostructures facilitate genetic modifications that result in the display of
      heterologous epitopes or antigens attached to coat proteins. These recombinant
      plant virus-based nanoparticles (PVNs) provide platforms for the induction of
      humoral and cellular immune responses to genetically fused antigens from
      pathogenic viruses, bacteria, tumors, and toxins in man and animals. Here, we
      comprehensively review the developments of several recombinant PVNs as
      prophylactic and/or therapeutic vaccines for the prevention or treatment of
      several microbial diseases, pathologies, and toxin poisoning.

PMID- 28440189
TI  - Better Predictive Value of Cancer Antigen125 (CA125) as Biomarker in Ovary and
      Breast Tumors and its Correlation with the Histopathological Type/Grade of the
      Disease.
AB  - BACKGROUND: Both ovarian/breast cancers are the most prevalent hormone-associated
      gynecological-cancers, where uncontrolled cellular proliferations/genetic-errors
      are noticed. The cancer-antigen125 (CA125), which we assessed presently is an
      important biomarker in the early detection/monitoring of this disease
      pathogenesis. METHODS: Serum/tissue CA125 was measured by solid-phase-Enzyme
      linked-immunosorbentassay in women with ovarian/breast tumors of different types
      (epithelial/non-epithelial; benign/ borderline/ malignant)/stages. Breast-tumor
      tissues were employed for histoarchitecture/DNAstability (comet) assay. Extensive
      protein-protein(CA125) interactions were studied by the STRING (Search-Tool-for
      the-Retrieval-of-Interacting Genes/Proteins) Bioinformatics-software. RESULTS:
      Serum CA125 levels were <35 U/ml in 94% of benign epithelial-cases, 35-65 U/ml in
      100% of borderline-tumors and >100 U/ml in the 41.17% of patients with malignant
      tumors. The malignant epithelial tumor showed significantly higher (>100U/ml)
      CA125 than the non-epithelial malignant-tumor (<35-65 U/ml). Highly enhanced
      cellularity/histo-architectural impairment/unstable- DNA-materials/CA125 was
      found in advanced breast-cancers. The CA125 is highly metabolically interactive,
      especially with mesothelin impairing cell-cell adhesion and enhancing tissue anti
      establishment. CONCLUSION: CA125 is a predictive-marker in ovarian/breast
      carcinoma depending on disease nature/stages. CA125, in combination with other
      tests like mesothelin/estradiol can be of great use in the better diagnosis of
      this disease. Not only as a detection-marker, has the CA125 played an interactive
      role in the disease processes. The Bioinformatics study revealed an important
      role of mesothelin and other mucin like proteins. Early detection and proper
      diagnosis are important determinants for the greater possibility of the relief
      from the disease like cancers. Selection of suitable biomarker combinations may
      increase the better diagnosis of the types and severity of this disease. Our
      present result has an impact on these aspects.

PMID- 28440190
TI  - Characterization of a Novel Polysaccharide-Iron(III) Complex and Its Anti-Anemia
      and Nonspecific Immune Regulating Activities.
AB  - OBJECTIVE: Dioscorea opposita Thunb is the famous food and traditional medicine
      in China and it was rich in polysaccharides. Polysaccharides of Dioscorea
      Opposita Thunb possess immunoregulatory activity, free radical scavenging
      activity and anti-diabetic activity. A novel polysaccharide- iron(III) complex
      (CYPIC) was synthesized by using crude polysaccharide extracted from Dioscorea
      opposita Thunb. The component, structure, morphology and molecular weights of
      CYPIC were analysed, and the anti-anemia, acute toxicity and nonspecific immune
      regulating activities of CYPIC were assayed. The results showed that CYPIC could
      increase red blood cell count (RBC), hemoglobin (Hb), hematocrit (HCT), thymus
      and spleen index of mice with iron deficiency anemia (IDA). Although the
      structure and deeper mechanisms of CYPIC should be further studied, CYPIC has the
      potential to be used as an iron supplement for the treatment of iron deficiency
      anemia. CONCLUSION: The large scale industrial production was suggested due to
      the simple preparation processing of CYPIC.

PMID- 28440188
TI  - TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids
      and Nociceptive Signalling.
AB  - BACKGROUND: Chronic pain is a significant clinical problem and a very complex
      pathophysiological phenomenon. There is growing evidence that targeting the
      endocannabinoid system may be a useful approach to pain alleviation. Classically,
      the system includes G protein-coupled receptors of the CB1 and CB2 subtypes and
      their endogenous ligands. More recently, several subtypes of the large
      superfamily of cation TRP channels have been coined as "ionotropic cannabinoid
      receptors", thus highlighting their role in cannabinoid signalling. Thus, the aim
      of this review was to explore the intimate connection between several "painful"
      TRP channels, endocannabinoids and nociceptive signalling. METHODS: Research
      literature on this topic was critically reviewed allowing us not only summarize
      the existing evidence in this area of research, but also propose several possible
      cellular mechanisms linking nociceptive and cannabinoid signaling with TRP
      channels. RESULTS: We begin with an overview of physiology of the endocannabinoid
      system and its major components, namely CB1 and CB2 G protein-coupled receptors,
      their two most studied endogenous ligands, anandamide and 2-AG, and several
      enzymes involved in endocannabinoid biosynthesis and degradation. The role of
      different endocannabinoids in the regulation of synaptic transmission is then
      discussed in detail. The connection between the endocannabinoid system and
      several TRP channels, especially TRPV1-4, TRPA1 and TRPM8, is then explored,
      while highlighting the role of these same channels in pain signalling.
      CONCLUSION: There is increasing evidence implicating several TRP subtypes not
      only as an integral part of the endocannabinoid system, but also as promising
      molecular targets for pain alleviation with the use of endo- and
      phytocannabinoids, especially when the function of these channels is upregulated
      under inflammatory conditions.

PMID- 28440191
TI  - Cannabis: A Neurological Remedy or a Drug of Abuse in India.
AB  - BACKGROUND: Since ancient times, the use of cannabis as a medicine is well
      documented due to its potential therapeutic activity while subsequently its use
      as drug of abuse spread increasingly. OBJECTIVE: The present review sought to
      give an insight in the history of medical and recreational use of cannabis in
      India. CONCLUSION: Indian use of cannabis dates back to Vedic time, mostly for
      the ritualistic and religious purposes, as documented in the ancient literature.
      It was India that introduced the medical use of cannabis to neighboring
      countries. Nevertheless, in the same India, medical use did not propagate due to
      religious and social stigma related to the plant itself. The pharmacoactive
      constituents of cannabis and their therapeutic values in Ayurvetic medicine have
      been here described together with the adverse effects they can cause with special
      reference to neurological ones, including withdrawal symptoms. Finally, how
      cannabis made its route to the Indian society has also been discussed.

PMID- 28440192
TI  - Mitochondrial Permeability Transition Pore as a Suitable Targ e t for
      Neuroprotective Agents Against Alzheimer's Disease.
AB  - BACKGROUND: A considerable amount of data suggests the age-related impairments of
      mitochondrial functions in the development of sporadic forms of neurodegenerative
      pathologies. Mitochondria and the phenomenon of mitochondrial permeability
      transition (MPT), which marks the point of no return in cell death cascades, have
      special value in this regard. It is important that the vulnerability to MPT
      inducing factors is increased with aging. Simultaneously, a decrease in the
      calcium retention capacity of mitochondria is developed, which leads to the
      disturbance of the functional activity of neurons. METHOD: The systematic
      investigations and web content related to the importance of MPT as the target for
      the search of neuroprotective and cognitive enhancing drugs, especially with
      multitargeted action, are reviewed. RESULTS: Here, we have highlighted some
      experimental data that determines the importance of mitochondria for the search
      of neuroprotective drugs, and drugs with multitargeted action. We have also
      discussed a number of new compounds with similar properties. Being MPT
      inhibitors/modulators, virtually all the compounds described in this review have
      the ability to exhibit a neuroprotective effect, interact with some other
      targets, providing coupled beneficial therapeutic effects such as cognitive
      stimulation, anti-seizure, and antidepressant actions. CONCLUSION: Inhibitors of
      MPT, which increases calcium retention capacity of mitochondria, are considered
      as promising neuroprotective drugs able not only to halt the neurodegenerative
      cascade, but also to increase the functional activity of neurons.

PMID- 28440193
TI  - Neurocognitive Correlates in Driving Under the Influence of Cannabis.
AB  - BACKGROUND & OBJECTIVE: Delta (9)-tetrahydrocannabinol (THC) is the main
      psychoactive compound in cannabis and is frequently identified in blood samples
      from apprehended drivers suspected for driving under the influence of drugs.
      Changing social norms towards cannabis and higher acceptability towards the drug
      emphasize the need for in-depth understanding of the acute neurocognitive and
      psychomotor effects caused by cannabis and how these effects are correlated to
      driving skills and performance. METHOD: In this review, PubMed, Cochrane Central,
      Scopus, Web of Science, Science Direct, EMBASE and Google Scholar databases were
      used to identify and select publications up to January 2017 dealing with acute
      and chronic neurocognitive effects induced by cannabis and ability to drive.
      Thirty-six publications were selected for this review. The studies conducted were
      experimental, using simulators or on-road studies and brain imaging (structural
      and functional) to better understand the acute and chronic effects on cognitive
      functions comprised in the short and long-term fitness to drive after cannabis
      consumption. CONCLUSION: In a case-crossover self-report study a significant odds
      ratio increase was found for driving- related injury after combined exposure to
      cannabis and alcohol compared to cannabis alone (OR of 10.9 and 5.8
      respectively). Both, experimental and epidemiological studies have revealed that
      THC affects negatively both, psychomotor skills and cognitive functions. Studies
      of the acute effects of cannabis on driving have shown that drivers under the
      influence of this substance are impaired. Indeed, driving under the influence of
      cannabis doubles or triples the risk of a crash. Specifically, cannabis use
      impairs critical-tracking tasks, increases lane weaving, decreases reaction time,
      and divided attention.

PMID- 28440194
TI  - Concurrent Use of Cannabis and Alcohol: Neuropsychiatric Effect Consequences.
AB  - BACKGROUND: Concurrent use of cannabis and alcohol is frequent. According
      different studies, the prevalence is among 20-34% depending on different samples
      studied. OBJECTIVE: In contrast with the wide evidence available about
      neuropsychiatric effects associated to the use of cannabis or alcohol separately,
      there are few studies of the neuropsychiatric effects of their combination. Our
      aim was to review the literature regarding this topic. CONCLUSION: We performed a
      search in MEDLINE and from 114 potentially eligible studies, 27 were selected.
      Most of them studied the relation between cannabis and alcohol, and with them
      combined to other substances of abuse, but only a few considered their concurrent
      effect among mental disorders (ADHD, bipolar disorder) and neuropsychological
      performance. More research in the neuropsychiatric effects of the concomitant use
      of cannabis and alcohol is needed.

PMID- 28440195
TI  - Editorial: New Insights into a Classical Pathway: Key Roles of the Mevalonate
      Cascade in Different Diseases (Part II).

PMID- 28440196
TI  - miR-126 as a Therapeutic Agent for Diabetes Mellitus.
AB  - Diabetes mellitus (DM) is a metabolic disorder which is characterized by
      inappropriate hyperglycemia. It is becoming an epidemic disease in developing
      countries. Diabetic patients are frequently afflicted with a vascular dysfunction
      and wound healing defect. In spite of intense investigations, over the past 2-3
      decades, optimal treatment options and related mechanisms are still unclear.
      MicroRNAs (miRNAs) are small noncoding RNAs considered as regulators of a vast
      number of biological processes including endothelial cell function controlling
      molecular signaling pathways in diabetic pathogenesis. Down regulation of
      microRNA-126 (miR-126) which may regulate angiogenesis and vascular integrity
      plays a significant role in the pathogenesis and complications of DM. This paper
      discusses the potential application of miR-126 as a novel therapeutic agent
      capable of reducing diabetic vascular complications in different types of DM
      based on the up-to-date reports.

PMID- 28440197
TI  - Hyperprolactinemia Induced by Antipsychotics: From Diagnosis to Treatment
      Approach.
AB  - Schizophrenia is one of the most severe psychiatric diseases with a significant
      impact on the psychosocial functioning of the patients. People with schizophrenia
      are at risk to die prematurely because of their illness with their poor lifestyle
      contributing to the excess morbidity and higher mortality rate. In particular,
      lifestyle (e.g. poor diet, low rates of physical activity and increased
      likelihood to smoke cigarettes) predisposes them to poor physical health and
      comorbid medical diseases. In addition, the treatment of schizophrenia usually
      involves the long-term administration of antipsychotic drugs and some of these
      medications are implicated in the increased risk of metabolic and cardiovascular
      effects. The antipsychotic-induced hyperprolactinemia was ascertained for the
      first time by Kleinberg in 1971 and was considered for this treatment.
      Antipsychotics are the most common pharmacological agents which cause
      hyperprolactinemia The aim of this review is to describe PRL physiology, PRL
      biological effects and pathway to the diagnosis, causes, consequences of HPRL
      focusing on the antipsychotic effects on the PRL. We conducted a review of
      studies published between 1974 and December 2014. The search was performed using
      the following PubMed search terms: "Hyperprolactinemia" and "antipsychotic" and
      827 papers were detected. The articles were examined and the overlapping or
      insufficiently clear works were excluded. Finally we chose 104 titles. We added
      to the selected articles additional articles, including 28 articles regarding the
      latest international guidelines, the pathophysiology of hyperprolactinemia and
      the various therapeutic choices.

PMID- 28440198
TI  - The Role of Neutrophil Proteases in LPS-Induced Production of Regulatory
      Rheumatoid Factor that Suppresses Autoimmunity.
AB  - BACKGROUND: We recently identified a regulatory rheumatoid factor (regRF), the
      production of which is associated with autoimmune disease resistance and
      remission. In studies of regRF in the blood of healthy rats, spontaneous
      increases in the regRF level were noted. We suggest that in the normal state, a
      mechanism exists for maintaining the activity of the pool of regRF-producing
      lymphocytes at a level that makes it possible to control the expansion of
      autoreactive lymphocytes. OBJECTIVE: The purpose of this study was to test the
      hypothesis that the endogenous stimulator of regRF production is Fc fragments of
      IgG that are formed upon exposure to the proteases of neutrophils. RESULTS:
      Injection of Salmonella typhi LPS caused neutrophilic leukocytosis in the rats,
      followed by elevated level of regRF. Neutrophils were obtained from LPS-treated
      rats and then treated with LPS in vitro to degranulate them to form pre-split IgG
      that exposes antigenic determinants for regRF. A condition required for Fc
      fragments to be formed by neutrophils is that the pre-split IgG must be treated
      with a thiol reducing agent. Antigenic determinants for regRF were retained by Fc
      fragments of IgG. CONCLUSION: Thus, the pre-split IgG and Fc fragments of IgG
      formed by LPS-activated neutrophils are the potential physiological activators of
      regRF production.

PMID- 28440199
TI  - Anti-Hyperglycemic Agents for the Treatment of Type 2 Diabetes Mellitus: Role in
      Cardioprotection During the Last Decade.
AB  - Type 2 diabetic patients are known to have a tendency to develop cardiovascular
      (CV) disease (CVD), and related unfavourable outcomes such as heart failure,
      myocardial infarction (MI), cerebrovascular events (e.g. stroke), and related
      mortality. Long- term clinical trials have revealed contradictory findings
      regarding the relationship between glycemic control and CV benefits due to
      variations in the key characteristics of the study population. During the last
      decade, number of pharmacological agents used for glucose- lowering in the
      treatment of type 2 diabetes mellitus (T2DM) has increased owing to the
      introduction of dipeptidyl peptidase- IV (DPP- IV) inhibitors, glucagon- like
      peptide- 1 (GLP- 1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT-
      2) inhibitors. This review aims to focus on the mechanisms of action of these
      drugs in the cardiovascular system and the trials evaluating their impact on CVD.
      Furthermore, trials in the last decade evaluating the impact of traditional
      glucose- lowering drugs on CVD are included. For this purpose, we searched PubMed
      for articles in English using the search terms "type 2 diabetes mellitus, glucose
      lowering drugs, antidiabetic medications, cardiovascular, cardiovascular
      disease, cardiovascular system" between inception to September 2016. We also
      searched separately for each medication in addition to the keyword
      "cardiovascular disease" on PubMed. To identify further articles, we hand
      searched related citations in review articles and commentaries.

PMID- 28440200
TI  - Effect of Halofuginone on the Pathogenesis of Autoimmune Thyroid Disease in
      Different Mice Models.
AB  - OBJECTIVE: Our objectives were to investigate the therapeutic effect of
      halofuginone (HF) in the treatment of autoimmune thyroid diseases (AITDs) and
      explore its underlying mechanism of action. METHODS: The Graves' disease (GD)
      model was generated by immunizing female BALB/c mice with adenovirus expressing
      the TSH receptor A subunit (Ad-TSHR289). The Ad-TSHRA+HF and Ad- TSHRA+DMSO
      groups were injected intraperitoneally with HF or the vehicle control (DMSO),
      respectively. The autoimmune thyroiditis (AIT) group consisted of female NOD.H
      2h4 mice that were administered NaI in the drinking water and intraperitoneally
      injected daily with the vehicle control (DMSO) during the study period. The
      AIT/HF group consisted of female NOD.H-2h4 mice that were administered NaI in the
      drinking water and intraperitoneally injected daily with HF. The frequencies of
      splenic Th17 cells, Tregs and Bregs were determined by flow cytometry. The mRNA
      levels of IL-17, forkhead box P3 (Foxp3), RORgammat and IL-10 were determined by
      real-time PCR. RESULTS: In both Ad-TSHRA+DMSO and Ad-TSHRA+HF groups, 10 out of
      15 mice displayed serum T4 and TSAb levels above 3 SD beyond the mean control
      levels. The number of CD4+CD25+Foxp3+ T lymphocytes in the GD model was
      significantly increased in the HF group compared with the DMSO group (P < 0.05).
      The mRNA level of Foxp3 was significantly increased in the Ad-TSHRA+HF group
      compared with the Ad-TSHRA+DMSO group (P < 0.05). However, neither the abundance
      of CD4+IL-17+ T cell subpopulation nor the mRNA expression level of RORgammat
      differed significantly between the Ad-TSHRA+HF and Ad-TSHRA+DMSO groups (P >
      0.05). The serum TgAb titer was significantly reduced in the AIT/HF group
      compared with the AIT group (P < 0.01). The differences in the number of
      CD4+CD25+Foxp3+ T lymphocytes and the mRNA levels of Foxp3 between the AIT/HF and
      AITgroups were not significant (P > 0.05). However, the number of CD4+IL-17+ T
      cells and the mRNA levels of IL-17 and RORgammat were significantly increased in
      HF-treated mice compared with the non-treated AIT-induced mice (P < 0.05).
      CONCLUSION: Treatment with HF significantly decreased the incidence of AIT by
      decreasing the number of CD4+IL-17+ T cells.

PMID- 28440201
TI  - Investigation of the pH Dependent Cytotoxicity of Paclitaxel Conjugated Gold
      Nanoparticles.
AB  - BACKGROUND: Breast cancer, apart from skin cancer, is the most common cancer
      among women accounting for nearly 1 in 3 cancers and the second leading cause of
      cancer-related death among women after lung cancer. Finding new approaches to
      treat such cancers is critically important. OBJECTIVE: This work investigated the
      ability of a simple system based on paclitaxel conjugated gold nanoparticles
      (AuNP) to induce efficient cytotoxicity against T47D breast cancerous cells at
      different pH values. METHODS: The synthesis and characterization of nanoparticles
      using two approaches are presented. In one case, the AuNP capping agent is
      exchanged for a long chained thiol with a terminal carboxylic acid which can then
      be connected to paclitaxel (termed the Chemical Modification approach) while in
      the other case, the thiol capping agent is chemically modified with the
      paclitaxel first and then exchanged onto the AuNP (termed the Ligand Exchange
      approach). Cytotoxicity of conjugates based on gold nanoparticles at pH 7.4
      (normal physiological pH) and 6.5 (more acidic pH found near tumors) against the
      T47D breast cancer cell line was assessed using the 3-(4, 5 dimethylthiazol-2-yl)
      2, 5- diphenyltetrazolium (MTT) viability assay. RESULTS: T47D viability
      decreased significantly after treatment with the chemical modification conjugate
      at pH 6.5 compared to that at pH 7.4. The ligand exchange conjugate also
      decreased cell viability with a gap of 10 % between the two pHs. CONCLUSION:
      These nanoparticles are promising conjugates for the treatment of breast cancer
      using small amounts of the active chemotherapy agents which will lead to fewer
      side effects.

PMID- 28440202
TI  - Oral Nano-Delivery Systems for Colon Targeting Therapy.
AB  - BACKGROUND: Targeting drug delivery is an attractive research area, as it enables
      localized treatment, improves the efficacy of therapeutics and reduces systemic
      toxicity. Colon targeting delivery is particularly beneficial to the treatment of
      colon diseases, such as inflammatory bowel disease and colon cancer, due to the
      improved local drug concentrations. The traditional strategies for colon
      targeting delivery include time-dependent and pH-dependent technologies, etc. In
      recent years, nanotechnology has emerged as a novel and efficient tool for
      targeting drug delivery. After oral administration, nano-based formulations are
      able to protect drug from the harsh gastrointestinal environment and selectively
      increase the drug concentration at the disease site. Various orally administered
      drug-loaded nano-systems for colon targeting delivery have been well documented
      and shown great potentials in colon disease therapy. OBJECTIVE: In this work, we
      aim to provide a comprehensive understanding of the recent progress in the area
      of colon targeting delivery in combination with introduction of the
      pathophysiological changes of diseased colon sites and the obstacles for drug
      delivery.

PMID- 28440203
TI  - Antimicrobial, Biofilm Inhibitory and Anti-infective Activity of Metallic
      Nanoparticles Against Pathogens MRSA and Pseudomonas aeruginosa PA01.
AB  - BACKGROUND: The emergence of drug resistant pathogens is a major concern to the
      scientific community. Novel approaches such as the use of functionalized
      nanomaterials with antimicrobial activity is required to treat infectious
      diseases. OBJECTIVE: In the present study, the metallic nanoparticles (iron,
      gold, zinc oxide and copper oxide) were evaluated for the antimicrobial, biofilm
      inhibitory and anti-infective activity against human pathogens methicillin
      resistant Staphylococcus aureus and Pseudomonas aeruginosa PA01. METHODS: The
      efficacy of nanoparticles on the planktonic growth of clinically relevant
      pathogens was determined by MIC. Further, the effect of nanoparticles was studied
      on their biofilms using crystal violet microtiter plate assay and fluorescent
      microscopy. The cytotoxicity of nanoparticles was studied in HT29 cell line.
      RESULTS: The nanoparticles of copper and zinc oxide (size < 50 nm) were more
      effective against Grampositive and Gram-negative pathogens in comparison to gold
      and iron nanoparticles. The ZnO nanoparticles had an MIC in the range of 3.125
      MUg/ ml and 6.25 MUg/ ml against the tested pathogens. The nanoparticles at the
      tested concentration reduced biofilm burden by > 75% in the pathogens. The
      nanoparticles showed cytotoxicity in HT 29 at 20 MUg/ ml. CONCLUSION: The results
      of the study showed that of all the tested nanoparticles, ZnO nanoparticles had
      significant antimicrobial activity against the drug resistant pathogens and could
      be used at concentrations less toxic to mammalian cells. Hence, ZnO nanoparticles
      have the potential for the design of novel antibacterial agents and therapeutics.

PMID- 28440204
TI  - Apixaban - Metabolism, Pharmacologic Properties and Drug Interactions.
AB  - BACKGROUND: Apixaban is an oral, potent, highly selective, reversible and direct
      inhibitor of activated coagulation factor X, that is the end point of the
      intrinsic and extrinsic coagulation pathway. Additionally, apixaban has the
      capacity to indirectly inhibit thrombin-induced platelet aggregation. This new
      oral anticoagulant represents an immediate-release form of peroral drug with
      quick dissolution, linear pharmacokinetics, good bioavailability and rapid onset
      and offset of action. No clinically relevant age- or sex-dependent difference in
      the apixaban pharmacokinetics and pharmacodynamics which would lead to the
      modification of the dose exists, apixaban may even be administered with or
      without food. Its elimination is mediated by metabolism, renal elimination of
      unmodified drug and excretion in the gastrointestinal tract. OBJECTIVE: The
      authors aim to provide a review of currently available literature about apixaban.
      METHOD: The authors summed-up the data from the scientific journals related to
      thrombosis and hemostasis and searched the available databases. RESULTS AND
      CONCLUSION: Apixaban has many advantages including predictable pharmacokinetics
      and pharmacodynamics, low number of drug and food interactions, and relatively
      wide therapeutic window.

PMID- 28440205
TI  - In Vitro Collapsing Colon Cancer Cells by Selectivity of Disulfiram-Loaded Charge
      Switchable Nanoparticles Against Cancer Stem Cells.
AB  - BACKGROUND: Different strategies against colon cancer are accompanied by
      treatment failure, because of drug toxicity toward normal cells and cancer stem
      cells (CSCs) resistance. However, previous patent evaluated liposome that
      encapsulated inhibitor of CSCs' aldehyde dehydrogenase (ALDH)1; disulfiram, for
      targeting breast CSCs. Liposome has disadvantages due to its hydrophobicity.
      OBJECTIVES: Designing hydrophilic nanoparticles has selectivity to release
      disulfiram in CC cells rather than in normal colonocytes based on variation in
      microenvironment between normal and cancer cells. METHODS: Disulfiram was
      nanoformulated by its loading into cationic chitosan and coating with anionic
      albumin. Their selectivity and targeting were investigated using murine and human
      colon cancer cells compared to normal mice colon cells. RESULTS: Zeta potential
      of the coated nanoparticles confirmed that albumin-layering confers negative
      charge (-10.3mv) for disulfiram-loaded chitosan nanoparticles (52.9mv). In
      slightly acidic medium of tumor, the ionic bond between albumin and chitosan
      hydrolyzed then the positive charge was reversed (47.6mv). Thus coated
      nanoparticles showed higher sustain release for disulfiram in tumor
      microenvironment than neutral pH and their uptake was higher in cancer cells than
      normal cells. This interpreted the highest selectivity of coated nanoparticles
      for enhancing apoptosis and eliminating CSCs in cancer cells. CONCLUSION: These
      patented coated nanoparticles were the most effective and selective for
      eradicating colon CSCs without insulting normal stem cells in comparison with
      disulfiram which was toxic to both normal and CSCs. This novel study that used
      charge switchable (hydrophilic) nanoparticles for targeting colon CSCs may
      represent a basis for future in vivo studies.

PMID- 28440206
TI  - Role of FoxM1 in the Progression and Epithelial to Mesenchymal Transition of
      Gastrointestinal Cancer.
AB  - Gastrointestinal (GI) cancer, characterized by its leading mortality, is one of
      the most common cancers worldwide. The underlying mechanisms contributing to
      epithelial to mesenchymal transition (EMT) and metastasis of GI cancer are poorly
      understood. It is well known that a great number of transcription factors
      including FoxM1, KLF4, STAT3 and so forth, are associated with the process of EMT
      and have also been strongly implicated in the proliferation, migration, and
      invasion of GI cancer cells. Forkhead box M1 (FoxM1), a transcription factor of
      the Forkhead family, is strongly positive in GI cancers and can be regarded as an
      oncogene in GI cancers. A number of studies have reported that FoxM1 is involved
      in tumorigenesis and promotes cell proliferation, migration, invasion,
      angiogenesis, EMT and metastasis by targeting downstream genes. In this review,
      we will focus on highlighting the functions of FoxM1 in tumorigenesis,
      angiogenesis, invasion and metastasis of GI cancers, pointing out the roles of
      FoxM1 in GI cancer EMT through crosstalk with TGFbeta, Wnt signaling pathways and
      ncRNA, to better understand the role of FoxM1 in GI cancer, and will discuss
      recent relevant patents concerning FoxM1 in tumor therapy.

PMID- 28440207
TI  - Epithelial Mesenchymal Transition in Cancer Progression: Prev entive
      Phytochemicals.
AB  - BACKGROUND: Epithelial-Mesenchymal Transition (EMT) is the conversion of
      epithelial cells into mesenchymal phenotype generally observed during
      embryogenesis and wound healing as well as in malignant transformation. Several
      signaling pathways and transcription factors associated with EMT have been
      explored. Dietary phytochemicals that are multi-targeted agents which interfere
      with these pathways, assume preventive potential against pathologic EMT.
      OBJECTIVE: The present review aims to provide a detailed description of the
      nature and characteristics of EMT in physiological and pathophysiological
      conditions and the scope of phytochemicals in its prevention. METHOD: Details
      regarding the initiation, progression as well as prevention of pathologic EMT and
      metastasis and recent patents on preventive phytochemicals were obtained from
      PubMed literatures and patent databases. RESULTS: The phenotypic changes during
      EMT are regulated by transcription factors like Snail, Slug, Twist and Zeb, which
      are activated through diverse signaling pathways of TGF-beta, NF-kB, Wnt and
      Notch. s phytocompounds that are potent enough to interfere with these signaling
      pathways, which in turn prevent pathological implications of EMT. Present review
      also discusses 28 recent patents on those phytocompounds. CONCLUSION: EMT is a
      significant pharmacological target for developing preventive agents to combat
      pathological conditions like malignancy. Many of the phytochemicals cited in this
      review are being enrolled for different phases of clinical trials for their
      efficacy. In spite of the major limitations regarding bioavailability,
      sensitivity and tolerance of these compounds, their synthetic analogs,
      formulations and efficient drug delivery systems are also being attempted which
      will hopefully generate productive and promising results in near future.

PMID- 28440208
TI  - Smoking, psychiatric illness and the brain.

PMID- 28440210
TI  - Pharmacotherapy of trichotillomania.

PMID- 28440212
TI  - Histological Evaluation of Decellularized Skeletal Muscle Tissue Using Two
      Different Decellularization Agents.
AB  - The aim of the present study was to determine effect of two decellularized
      agents, sodium dodecyl sulphate (SDS) and Triton X-100, to the skeletal muscle
      tissue. Final scaffold was evaluated by several histological techniques to
      analyse preservation of essential structures including collagen and elastic
      fibres, basement membranes, glycosaminoglycans and also to confirm elimination of
      nuclear and cytoplasmic components which are redundant in effectively prepared
      decellularized scaffolds. Comparison of tissue scaffolds processed with different
      detergents proved that SDS is superior to Triton X-100 as it can effectively
      decellularize muscle tissue.

PMID- 28440213
TI  - Clinical Study of 23 Male Patients with Congenital Ventral Penile Angulation
      without Hypospadias.
AB  - Congenital ventral penile angulation without hypospadias is a rare disease and
      causes great anxiety to the parents. The aim of our study is the presentation of
      this disease, especially the indications of surgical treatment and the protocol
      applied in our clinic. We retrospectively studied 23 male patients aged 2.5 to 7
      years old (av 5.2 y) with important penile angulation (over 45 degrees ) without
      hypospadias, treated during the past 15 years in our department. In 9 patients
      the cause was the skin chordee (fibrosis of the ventral part of the prepuce), in
      4 the fibrotic fascia (incomplete development of dartos and Buck's fascia) and in
      10 the disproportion of the corpora cavernosa. No case of congenital short
      urethra was reported. In our opinion, the appliance of the algorithm suggested by
      Donnahoo KK et al. in uncomplicated cases, along with the experience of the
      surgical team, results in satisfactory treatment and avoidance of complications.

PMID- 28440211
TI  - A cluster randomised trial, cost-effectiveness analysis and psychosocial
      evaluation of insulin pump therapy compared with multiple injections during
      flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial.
AB  - BACKGROUND: Insulin is generally administered to people with type 1 diabetes
      mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered
      using infusion pumps. In the UK, pumps are recommended for patients with the
      greatest need and adult use is less than in comparable countries. Previous trials
      have been small, of short duration and have failed to control for training in
      insulin adjustment. OBJECTIVE: To assess the clinical effectiveness and cost
      effectiveness of pump therapy compared with MDI for adults with T1DM, with both
      groups receiving equivalent structured training in flexible insulin therapy.
      DESIGN: Pragmatic, multicentre, open-label, parallel-group cluster randomised
      controlled trial, including economic and psychosocial evaluations. After
      participants were assigned a group training course, courses were randomly
      allocated in pairs to either pump or MDI. SETTING: Eight secondary care diabetes
      centres in the UK. PARTICIPANTS: Adults with T1DM for > 12 months, willing to
      undertake intensive insulin therapy, with no preference for pump or MDI, or a
      clinical indication for pumps. INTERVENTIONS: Pump or MDI structured training in
      flexible insulin therapy, followed up for 2 years. MDI participants used insulin
      analogues. Pump participants used a Medtronic Paradigm(r) VeoTM (Medtronic,
      Watford, UK) with insulin aspart (NovoRapid, Novo Nordisk, Gatwick, UK). MAIN
      OUTCOME MEASURES: Primary outcome - change in glycated haemoglobin (HbA1c) at 2
      years in participants whose baseline HbA1c was >= 7.5% (58 mmol/mol). Key
      secondary outcome - proportion of participants with HbA1c <= 7.5% at 2 years.
      Other outcomes at 6, 12 and 24 months - moderate and severe hypoglycaemia;
      insulin dose; body weight; proteinuria; diabetic ketoacidosis; quality of life
      (QoL); fear of hypoglycaemia; treatment satisfaction; emotional well-being;
      qualitative interviews with participants and staff (2 weeks), and participants (6
      months); and ICERs in trial and modelled estimates of cost-effectiveness.
      RESULTS: We randomised 46 courses comprising 317 participants: 267 attended a
      Dose Adjustment For Normal Eating course (132 pump; 135 MDI); 260 were included
      in the intention-to-treat analysis, of which 235 (119 pump; 116 MDI) had baseline
      HbA1c of >= 7.5%. HbA1c and severe hypoglycaemia improved in both groups. The
      drop in HbA1c% at 2 years was 0.85 on pump and 0.42 on MDI. The mean difference
      (MD) in HbA1c change at 2 years, at which the baseline HbA1c was >= 7.5%, was 
      0.24% [95% confidence interval (CI) -0.53% to 0.05%] in favour of the pump (p =
      0.098). The per-protocol analysis showed a MD in change of -0.36% (95% CI -0.64%
      to -0.07%) favouring pumps (p = 0.015). Pumps were not cost-effective in the base
      case and all of the sensitivity analyses. The pump group had greater improvement
      in diabetes-specific QoL diet restrictions, daily hassle plus treatment
      satisfaction, statistically significant at 12 and 24 months and supported by
      qualitative interviews. LIMITATION: Blinding of pump therapy was not possible,
      although an objective primary outcome was used. CONCLUSION: Adding pump therapy
      to structured training in flexible insulin therapy did not significantly enhance
      glycaemic control or psychosocial outcomes in adults with T1DM. RESEARCH
      PRIORITY: To understand why few patients achieve a HbA1c of < 7.5%, particularly
      as glycaemic control is worse in the UK than in other European countries. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN61215213. FUNDING: This project was
      funded by the National Institute for Health Research (NIHR) Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 21, No. 20. See the NIHR Journals Library website for further
      project information.

PMID- 28440214
TI  - Common Mistakes in the Dual-Energy X-ray Absorptiometry (DXA) in Turkey. A
      Retrospective Descriptive Multicenter Study.
AB  - BACKGROUND: Osteoporosis is a widespread metabolic bone disease representing a
      global public health problem currently affecting more than two hundred million
      people worldwide. The World Health Organization states that dual-energy X-ray
      absorptiometry (DXA) is the best densitometric technique for assessing bone
      mineral density (BMD). DXA provides an accurate diagnosis of osteoporosis, a good
      estimation of fracture risk, and is a useful tool for monitoring patients
      undergoing treatment. Common mistakes in BMD testing can be divided into four
      principal categories: 1) indication errors, 2) lack of quality control and
      calibration, 3) analysis and interpretation errors, and 4) inappropriate
      acquisition techniques. The aim of this retrospective multicenter descriptive
      study is to identify the common errors in the application of the DXA technique in
      Turkey. METHODS: All DXA scans performed during the observation period were
      included in the study if the measurements of both, the lumbar spine and proximal
      femur were recorded. Forearm measurement, total body measurements, and
      measurements performed on children were excluded. Each examination was surveyed
      by 30 consultants from 20 different centers each informed and trained in the
      principles of and the standards for DXA scanning before the study. RESULTS: A
      total of 3,212 DXA scan results from 20 different centers in 15 different Turkish
      cities were collected. The percentage of the discovered erroneous measurements
      varied from 10.5% to 65.5% in the lumbar spine and from 21.3% to 74.2% in the
      proximal femur. The overall error rate was found to be 31.8% (n = 1021) for the
      lumbar spine and 49.0% (n = 1576) for the proximal femur. CONCLUSION: In Turkey,
      DXA measurements of BMD have been in use for over 20 years, and examination
      processes continue to improve. There is no educational standard for operator
      training, and a lack of knowledge can lead to significant errors in the
      acquisition, analysis, and interpretation.

PMID- 28440215
TI  - Fibroblast Growth Factor-1 Suppresses TGF-beta-Mediated Myofibroblastic
      Differentiation of Rat Hepatic Stellate Cells.
AB  - Myofibroblast expansion is a critical event in the pathogenesis of liver
      fibrosis. The activation of hepatic stellate cells (HSC) to myofibroblast (MFB)
      results in the enhanced production of extracellular matrix (ECM). In this study,
      we explored the effect of acidic fibroblast growth factor (FGF-1) treatment on a
      transforming growth factor (TGF-beta1) induced MFB conversion. We used HSC-T6
      cell line, which represents well-established model of activated HSC. These cells
      strongly expressed alpha-smooth muscle actin (alpha-SMA) and fibronectin (FN-EDA)
      after stimulation with TGF-beta1, which is a stimulus for MFB differentiation and
      ECM production. FGF-1 reduced proteins expression to levels comparable with
      untreated cells. Mild repression of secreted gelatinases was seen in culture
      media after FGF-1 treatment. The exposure of cells to collagen gel leads to
      changes in cell morphology and in expression of MFB markers. Lack of alpha-SMA in
      cells embedded to collagen gel was detected. When stimulated with TGF-beta1, the
      cells increased expression of FN-EDA, but not alpha-SMA. Although the cells on
      plastic and in collagen gel show different properties, FGF-1 reduced expression
      of FN-EDA in both conditions. Disrupting TGF-beta1 signalling pathway represents
      a potential strategy for the treatment of fibrosis. We showed that FGF-1 could
      antagonize signals initiated by TGF-beta1.

PMID- 28440216
TI  - Transseptal Suturing Reduce Patient Anxiety after Septoplasty Compared to Nasal
      Packing.
AB  - BACKGROUND: We measured postoperative anxiety in patients who underwent
      transseptal suturing or nasal packing after septoplasty. MATERIALS AND METHODS:
      Transseptal suturing was performed on Group 1 patients and nasal splints with
      airway were placed after septoplasty in Group 2 patients. Postoperative 48-h
      anxiety levels of both groups were measured using the State-Trait Anxiety
      Inventory (STAI) clinical assessment scale, prior to removal of nasal packing in
      Group 2. RESULTS: Transseptal suturing was performed after septoplasty in 28
      patients and nasal packing in 34 patients. The State-Trait Anxiety Inventory
      clinical assessment state (STAI-S) and trait (STAI-T) instruments were used to
      measure postoperative anxiety. The STAI-S scores were found 35.00 in the
      transseptal suturing group and 43.8 in the nasal packing group; the difference
      was found significant (p < 0.05). The STAI-T scores were found 42.6 in the
      transseptal suturing group and 45.7 in the nasal packing group; the difference
      was not found significant (p > 0.05). The rate of minor hemorrhage was found
      10.7% in Group 1 patients. CONCLUSIONS: Transseptal suturing is simple and
      reliable when performed after septoplasty. The technique is painless and
      comfortable, and reduces patient anxiety (compared to that associated with nasal
      packing) with only a minor increase in operating time and hemorrhage.

PMID- 28440217
TI  - Intraparenchymal Epididymal Cyst (IEC) 4 cm in Diameter in a 15-Year Old Male
      Patient; a Case Report and Review of the Literature.
AB  - Intraparenchymal epididymal cysts (IECs) are benign cystic formations of the
      epididymis of unknown pathogenesis, which typically appear in adolescence or
      adulthood. In patients older than 14 years old their prevalence is doubled. After
      systematic and thorough research of the current literature, we did not find
      another case report of intraparenchymal epididymal cyst with similar dimensions.
      The male patient, 15 years old, visited our outpatient department complaining of
      pain in the right hemiscrotum. Diagnosis of IEC was confirmed after the
      conduction of ultrasound examination. Patient underwent surgical exploration of
      the right hemiscrotum. Resection of the IEC followed. Postoperative course was
      uneventful, with recession of the symptoms. In our opinion, IECs should be
      surgically removed, either when they are symptomatic or when they are
      asymptomatic, but of a diameter greater than 1 cm and without regression
      tendency.

PMID- 28440218
TI  - A Case of 2-Year-Old Child with Entero-Enteric Fistula Following Ingestion of 25
      Magnets.
AB  - INTRODUCTION: Magnet ingestion usually does not cause serious complications, but
      in case of multiple magnet ingestion or ingestion of magnet with other metal it
      could cause intestinal obstruction, fistula formation or even perforation. CASE
      REPORT: We report case of intestinal obstruction and fistula formation following
      ingestion of 25 magnets in a 2-year-old girl. Intraoperatively omega shaped
      intestinal loop with fistula caused by two magnetic balls was found. Intestine
      trapped with magnetic balls was edematous and inflamed. Resection of intestinal
      segment was performed, followed by entero-enteric anastomosis. A total of 25
      magnets were removed from resected intestine. CONCLUSION: Single magnet ingestion
      is treated as non-magnetic foreign body. Multiple magnet ingestion should be
      closely monitored and surgical approach could be the best option to prevent or to
      cure its complications.

PMID- 28440219
TI  - Correction: An alternative splicing switch shapes neurexin repertoires in
      principal neurons versus interneurons in the mouse hippocampus.

PMID- 28440220
TI  - Rapid evolution of the human mutation spectrum.
AB  - DNA is a remarkably precise medium for copying and storing biological
      information. This high fidelity results from the action of hundreds of genes
      involved in replication, proofreading, and damage repair. Evolutionary theory
      suggests that in such a system, selection has limited ability to remove genetic
      variants that change mutation rates by small amounts or in specific sequence
      contexts. Consistent with this, using SNV variation as a proxy for mutational
      input, we report here that mutational spectra differ substantially among species,
      human continental groups and even some closely related populations. Close
      examination of one signal, an increased TCC->TTC mutation rate in Europeans,
      indicates a burst of mutations from about 15,000 to 2000 years ago, perhaps due
      to the appearance, drift, and ultimate elimination of a genetic modifier of
      mutation rate. Our results suggest that mutation rates can evolve markedly over
      short evolutionary timescales and suggest the possibility of mapping mutational
      modifiers.

PMID- 28440221
TI  - NPTX2 and cognitive dysfunction in Alzheimer's Disease.
AB  - Memory loss in Alzheimer's disease (AD) is attributed to pervasive weakening and
      loss of synapses. Here, we present findings supporting a special role for
      excitatory synapses connecting pyramidal neurons of the hippocampus and cortex
      with fast-spiking parvalbumin (PV) interneurons that control network excitability
      and rhythmicity. Excitatory synapses on PV interneurons are dependent on the AMPA
      receptor subunit GluA4, which is regulated by presynaptic expression of the
      synaptogenic immediate early gene NPTX2 by pyramidal neurons. In a mouse model of
      AD amyloidosis, Nptx2-/- results in reduced GluA4 expression, disrupted
      rhythmicity, and increased pyramidal neuron excitability. Postmortem human AD
      cortex shows profound reductions of NPTX2 and coordinate reductions of GluA4.
      NPTX2 in human CSF is reduced in subjects with AD and shows robust correlations
      with cognitive performance and hippocampal volume. These findings implicate
      failure of adaptive control of pyramidal neuron-PV circuits as a
      pathophysiological mechanism contributing to cognitive failure in AD.

PMID- 28440222
TI  - Dual leucine zipper kinase-dependent PERK activation contributes to neuronal
      degeneration following insult.
AB  - The PKR-like endoplasmic reticulum kinase (PERK) arm of the Integrated Stress
      Response (ISR) is implicated in neurodegenerative disease, although the
      regulators and consequences of PERK activation following neuronal injury are
      poorly understood. Here we show that PERK signaling is a component of the mouse
      MAP kinase neuronal stress response controlled by the Dual Leucine Zipper Kinase
      (DLK) and contributes to DLK-mediated neurodegeneration. We find that DLK
      activating insults ranging from nerve injury to neurotrophin deprivation result
      in both c-Jun N-terminal Kinase (JNK) signaling and the PERK- and ISR-dependent
      upregulation of the Activating Transcription Factor 4 (ATF4). Disruption of PERK
      signaling delays neurodegeneration without reducing JNK signaling. Furthermore,
      DLK is both sufficient for PERK activation and necessary for engaging the ISR
      subsequent to JNK-mediated retrograde injury signaling. These findings identify
      DLK as a central regulator of not only JNK but also PERK stress signaling in
      neurons, with both pathways contributing to neurodegeneration.

PMID- 28440224
TI  - Identifying faulty brain circuits.
AB  - A protein called NPTX2 may be a useful marker of neural circuit defects in
      patients with Alzheimer's disease.

PMID- 28440223
TI  - Structural insights into the molecular mechanisms of myasthenia gravis and their
      therapeutic implications.
AB  - The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies
      in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular
      transmission dysfunction. Despite decades of research, the molecular mechanisms
      underlying MG have not been fully elucidated. Here, we present the crystal
      structure of the nAChR alpha1 subunit bound by the Fab fragment of mAb35, a
      reference monoclonal antibody that causes experimental MG and competes with ~65%
      of antibodies from MG patients. Our structures reveal for the first time the
      detailed molecular interactions between MG antibodies and a core region on nAChR
      alpha1. These structures suggest a major nAChR-binding mechanism shared by a
      large number of MG antibodies and the possibility to treat MG by blocking this
      binding mechanism. Structure-based modeling also provides insights into antibody
      mediated nAChR cross-linking known to cause receptor degradation. Our studies
      establish a structural basis for further mechanistic studies and therapeutic
      development of MG.

PMID- 28440225
TI  - Observation of nonanoic acid and aldehydes in exhaled breath of patients with
      lung cancer.
AB  - Lung cancer (LC) is the leading cause of cancer death in men and the second
      leading cause in women worldwide. The use of low-dose computed tomography in
      early diagnosis was shown to reduce mortality by 20% with a median follow-up time
      of 6.5 years. In order to increase profitability and reduce radiation risks and
      costs, exhaled biomarkers could serve to help establish narrower inclusion
      criteria. The aim of this study was to identify new, well-founded volatile
      organic compounds in exhaled breath which distinguish LC patients from chronic
      obstructive pulmonary disease (COPD) patients and healthy subjects. There were
      210 subjects enrolled and divided into three groups: control group (n = 89), COPD
      group (n = 40 stable COPD patients) and LC group (n = 81 with histological
      confirmation). Exhaled breath samples were collected using BioVOC(r) breath
      sampler devices. The analytical technique used was thermal desorption-gas
      chromatography-mass spectrometry. The compounds studied were hexanal, heptanal,
      octanal, nonanal, propanoic and nonanoic acids. Nonanoic acid showed
      statistically significant differences between the LC group and the other groups.
      It is 2.5 times and almost 9 times more likely to be found in the LC group than
      in the control group or COPD group, respectively. It is independent of histology
      but depends on tumour stage.

PMID- 28440226
TI  - Calibration phantoms for accurate water and lipid density quantification using
      dual energy mammography.
AB  - The aim of this study is to investigate the feasibility of water and lipid as
      calibration phantoms for accurate dual energy breast density quantification. Dual
      energy calibration was performed on a mammography system based on scanning multi
      slit Si strip photon-counting detectors using plastic water and adipose
      equivalent phantoms as the basis materials. Two different methods were used to
      convert the dual energy decomposition measurements in plastic phantom thicknesses
      into the true water and lipid basis materials. The first method was based
      entirely on the theoretically calculated effective attenuation coefficients of
      the investigated materials in the mammographic energy range. The conversion
      matrix was determined through the linear least-squares fitting of the target
      material using the calculated effective attenuation coefficients of water and
      lipid. The second method was based on experimental calibration with plastic water
      phantom, adipose-equivalent phantom, and its correlation to known water and lipid
      thicknesses. These two methods were then validated by using an independent
      measurement of water and lipid mixture phantoms and postmortem breasts. The
      correlation between the dual energy decomposition measurements and the known
      values was evaluated using linear regression analysis. The averaged root-mean
      square errors for water density quantification derived from the theoretical and
      experimental conversions were 8.6% and 1.6%, respectively. The postmortem breast
      tissue study also indicates that the experimentally acquired conversion
      coefficient improved the accuracy in water density quantification, in comparison
      with that from the theoretical conversion. The results show that conversion of
      the dual energy measurements into water and lipid thicknesses improves the
      accuracy in breast tissue decomposition.

PMID- 28440227
TI  - 3D silicon shapes through bulk nano structuration by focused ion beam
      implantation and wet etching.
AB  - The work presented in this paper concerns the synthesis of silicon (Si) 2D and 3D
      nanostructures using the delayed effect, caused by implanted Ga ions, on the
      dissolution of Si in aqueous solutions of tetramethylammonium hydroxide (TMAH).
      The crystalline silicon substrates (100) are first cleaned and then hydrogenated
      by immersion in an aqueous solution of hydrofluoric acid. The ion implantation is
      then carried out by a focused ion beam by varying the dose and the exposure time.
      Chemical etching in aqueous solutions of TMAH at 80  degrees C leads to the
      selective dissolution of the Si planes not exposed to the ions. The preliminary
      results obtained in the laboratory made it possible to optimize the experimental
      conditions for the synthesis of 2D and 3D nanoobjects of controlled shape and
      size. Analysis by transmission electron microscopy and energy dispersive x-ray
      showed the amorphous nature of the nanostructures obtained and the presence of 5%
      20% Ga in these nanoobjects. The first experiments of recrystallization by rapid
      thermal annealing allowed to reconstitute the crystal structure of these
      nanoobjects.

PMID- 28440228
TI  - Clinicoepidemiologic study of verruca plana at a tertiary care center.

PMID- 28440229
TI  - Pigmented fungiform papillae in mother and daughter.

PMID- 28440230
TI  - Extensive milia formation in a young woman with bullous pemphigoid.

PMID- 28440231
TI  - Multiple asymptomatic hard papules on cheeks in an elderly woman.

PMID- 28440233
TI  - "Clinical" cytology for endoscopists: A practical guide.
AB  - Clinical cytology was originally used by clinicians to provide rapid diagnosis.
      However, with advancing medical subspecialization, few clinicians interpret
      cytology themselves these days, for example, gynecologists, hematologists,
      urologists, and occasional gastroenterologist (mainly in Asian countries).
      Cytological assessment enjoyed a renaissance with the development of endoscopic
      ultrasound (EUS)-guided fine-needle aspiration (FNA). Subsequently, pathologists,
      most of them more experienced in histology, had to take over. Recently, it has
      been shown that in-room cytology can be easily performed by the endoscopist
      themselves for initial evaluation of the quality of the EUS-FNA specimen and an
      initial diagnosis distinguishing benign or malignant cells. Bringing cytology
      back to the clinician has some advantages but does not substitute the
      professional cytopathologist. This report has written to lower the threshold for
      the clinician to find his way back to the microscope, which may improve both
      their diagnostic yield and assessment of EUS-FNA sample quality.

PMID- 28440234
TI  - Endoscopic ultrasound of peritoneal spaces.
AB  - The peritoneal cavity is subdivided into supracolic and infracolic compartments
      by transverse colon and its mesocolon. The supracolic compartment contains the
      liver, spleen, stomach, and lesser omentum. The infracolic compartment contains
      the coils of small bowel surrounded by ascending, transverse, and descending
      colon and the paracolic gutters. The imaging of different compartments is
      possible by various methods such as ultrasound (US) and computerized tomography.
      The treating physicians should be familiar with the relevant radiological anatomy
      of different compartments and spaces as accurate localization of fluid
      collection/lymph node in peritoneal cavity greatly aids in selection of a
      treatment strategy. The role of endoscopic US (EUS) is emerging for detail
      evaluation of all parts of peritoneal cavity as it provides an easy access for
      fine-needle aspiration from different compartments of peritoneal cavity. In this
      review, we describe the techniques of evaluation of different parts of supracolic
      compartments of peritoneum by EUS.

PMID- 28440232
TI  - Clinical use of endoscopic ultrasound-guided fine-needle aspiration: Guidelines
      and recommendations from Chinese Society of Digestive Endoscopy.

PMID- 28440235
TI  - The effect of solid pancreatic mass lesions on pancreatic duct diameter at
      endoscopic ultrasound.
AB  - OBJECTIVES: To evaluate the effect of solid pancreatic masses on the pancreatic
      duct (PD) at the endoscopic ultrasound (EUS) and the relationship of the
      location/size of a mass and PD dilation. MATERIALS AND METHODS: Patients who
      underwent EUS for pancreatic indications from 2011 to 2013 at a single center
      were retrospectively identified. Those with biopsies that revealed adenocarcinoma
      or neuroendocrine tumors in the pancreas were identified and PD size was
      ascertained from EUS, computed tomography, or magnetic resonance imaging.
      RESULTS: Of the 475 patients who had a pancreatic EUS, 239 had a dilated PD and
      236 had a normal PD. Patients with a dilated PD had a significantly higher
      incidence of pancreatic malignancy than those with a normal PD diameter (106/239,
      44.4% vs. 32/236, 13.6%, P< 0.001). Of the 138 patients with a pancreatic
      malignancy, 106 (76.8%) had a dilated PD at some location in the pancreas. Over
      80% of patients with a mass within the head, neck, or body had a dilated PD. For
      a mass located at the uncinate process or the tail, PD dilation was 65% and 23%,
      respectively. Fifty-six (80.0%) of the masses in the head, 11 (78.6%) masses in
      the neck, and 16 (76.2%) masses in the body had a dilated PD upstream of the
      mass. In addition, a step-wise increase in the incidence of PD dilation was
      correlated with an increase in mass size. About 67.6% of patients with masses
      measuring in the 1st quartile had dilated a PD, while 77.8%, 91.0%, and 71.4% of
      those with masses measuring in the 2nd, 3rd, and 4th quartiles, respectively, had
      a dilated PD. CONCLUSION: PD dilation is a warning sign for pancreatic
      malignancies, however, small masses or masses at the uncinate process or the tail
      of the pancreas may not affect the size of the PD.

PMID- 28440236
TI  - Endoscopic ultrasound-guided fine-needle aspiration can target right liver mass.
AB  - BACKGROUND AND OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration
      (EUS-FNA) has been established as a safe and accurate method for diagnosing and
      staging intra-abdominal mass. However, few studies investigated its feasibility,
      efficacy, and safety for targeting liver mass. We evaluated the efficacy and
      safety of EUS-FNA in patients with liver masses including the right lobe.
      PATIENTS AND METHODS: The technical feasibility, safety, and diagnostic yield
      were determined in 47 patients (30 in the left lobe and 17 in the right lobe)
      presenting with liver masses between September 2010 and February 2016. RESULTS:
      Thirty-eight patients (80.9%) had malignancies whereas nine patients (19.1%) had
      benign liver masses. Technical success rate was 97.9% (46/47). EUS-FNA was
      diagnostic in 38 of 42 patients (90.5%). When the outcomes of EUS-FNA between
      right liver mass and left mass were accessed, the technical success rates were
      similar in both lobes (100% vs. 94.1%, P= 0.2). The median tumor size on EUS
      (25.5 mm, interquartile range [IQR] 13.8-30.3 vs. 28 mm, IQR 18.5-43.5, P= 0.24)
      and number of needle passes (3, IQR 3-4 vs. 3, IQR 3-3, P= 0.24) were not
      significantly different. Adequate specimen obtained was statistically higher in
      the left lobe (28/30, 93.3% vs. 14/17, 82.4%, P= 0.04). However, diagnostic
      accuracy for liver masses was not different (25/28, 89.3% vs. 13/14, 92.9%, P=
      0.86). No complications developed after procedure. CONCLUSIONS: EUS-FNA can be a
      safe and efficient method for the diagnosis of liver mass and it is technically
      feasible even for those in the right lobe.

PMID- 28440237
TI  - New criteria to differentiate between mucinous cystic neoplasm and serous cystic
      neoplasm in pancreas by endoscopic ultrasound: A preliminarily confirmed outcome
      of 41 patients.
AB  - BACKGROUND AND OBJECTIVES: The ability to distinguish between mucinous cystic
      neoplasm (MCN) and serous cystic neoplasm (SCN) in the pancreas preoperatively by
      endoscopic ultrasound (EUS) remains a clinical challenge. To address this
      problem, we have developed new criteria using EUS findings and cyst fluid
      carcinoembryonic antigen (CEA) in the clinic. In this study, the validity and
      reliability of these criteria were assessed. MATERIALS AND METHODS: Between April
      of 2015 and May of 2016, a total of 59 patients with pancreatic cystic neoplasms
      underwent EUS and ultimately received surgery in our hospital. Of the 59
      patients, 21 were pathologically verified to have MCN while 20 were verified to
      have SCN in the pancreas. For these 41 patients with MCN or SCN, EUS findings and
      cyst fluid CEA were reviewed. RESULTS: For the 41 patients reviewed, the new
      criteria were found to identify MCN with 85.71% sensitivity (95% confidence
      interval [CI], 64%-97%), 80.00% specificity (CI, 56%-94%), and 82.93% accuracy
      (CI, 68%-93%). CONCLUSION: These new criteria were preliminarily found to produce
      excellent results, with 82.93% accuracy determined for the differential diagnosis
      between MCN and SCN by EUS. However, a further prospective study with a larger
      population must be carried out to fully assess these new criteria.

PMID- 28440238
TI  - Thermal ablation of pancreatic cyst with a prototype endoscopic ultrasound
      capable radiofrequency needle device: A pilot feasibility study.
AB  - BACKGROUND AND OBJECTIVES: Pancreatic cysts are evaluated by endoscopic
      ultrasound and fine needle aspiration (EUS). The only accepted treatment is
      pancreatectomy, which is associated with morbidity and mortality. This study
      evaluated the optimal thermal dosimetry of a novel radiofrequency ablation device
      using a standard electrosurgical unit in ex vivo cyst models. METHODS: A modified
      EUS 22-gauge monopolar needle prototype with a tip electrode connected to a
      standard electrosurgical unit (Erbe USA, Marietta, GA, USA) was used to induce a
      subboiling point temperature. A cyst model was created using 2-cm sections of
      porcine small intestine ligated and filled with saline. After ablation, the cyst
      models were prepared for pathological evaluation. The epithelial layers were
      measured in at least two different sites with a micrometer and compared with the
      corresponding control sample. RESULTS: Thirty-two cyst models were ablated with
      maximum temperatures of 50 degrees C, 60 degrees C, 90 degrees C, and 97 degrees
      C in 8, 11, 11, and 2 cysts, respectively. Longer ablation times were required to
      induce higher temperatures. A trend in the reduction in thickness of the measured
      layers was observed after exposure to higher temperatures. A temperature over 50
      degrees C was required for the ablation of the muscularis, submucosa, and villi,
      and over 60 degrees C was required to ablate the mucosal crypts. CONCLUSIONS: In
      a preclinical model, a novel radiofrequency EUS-capable needle connected to a
      standard electrosurgical unit using standard low-voltage coagulation provided
      ablation in a temperature-dependent fashion with a threshold of at least 60
      degrees C and a safe cyst margin below 97 degrees C. This potentially will allow
      low-cost, convenient cyst ablation.

PMID- 28440239
TI  - Feasibility, safety, and outcomes of a single-step endoscopic ultrasonography
      guided drainage of pancreatic fluid collections without fluoroscopy using a novel
      electrocautery-enhanced lumen-apposing, self-expanding metal stent.
AB  - BACKGROUND AND OBJECTIVES: There are currently limited data available regarding
      the safety of endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid
      collections (PFCs) using the lumen-apposing metal stent without fluoroscopic
      guidance. This study aims to evaluate clinical outcomes and safety of EUS-guided
      drainage of PFC using the electrocautery-enhanced lumen-apposing metal stents (EC
      LAMSs) without fluoroscopic guidance. METHODS: We conducted a retrospective study
      on patients with symptomatic PFC who underwent EUS-guided drainage using EC-LAMS
      without fluoroscopy. All patients were followed clinically until resolution of
      their PFC. Technical success (successful placement of EC-LAMS), number of
      patients who achieved complete resolution of PFC without additional intervention
      and adverse events were noted. RESULTS: We evaluated 25 patients, including three
      with pancreatic pseudocysts and 22 with walled-off necrosis (WON). The etiology
      of the patient's pancreatitis was gallstones (42%), alcohol (27%), and other
      causes (31%). The mean cyst size was 82 mm (range, 60-170 mm). The indications
      for endoscopic drainage were abdominal pain, infected WON, or gastric outlet
      obstruction. Technical success with placement of the EC-LAMS was achieved in all
      25 patients. There were no procedure-related complications. The mean patient
      follow-up was 7.8 months. PFCs resolved in 24 (96%) patients; the one failure was
      in a patient with WON. Stent occlusion was seen in one patient. There was a
      spontaneous migration of one stent into the enteral lumen after resolution of
      WONs. The EC-LAMS were successfully removed using a snare in all the remaining
      patients. The median number of endoscopy sessions to achieve PFCs resolution was
      2 (range, 2-6). CONCLUSIONS: Single-step EUS-guided drainage of PFCs without
      fluoroscopic guidance using the novel EC-LAMS is a safe and effective endoscopic
      technique for drainage of PFCs with excellent technical and clinical success
      rates and no complications. Due to its ease of use, EC-LAMS may simplify and
      streamline EUS-guided management of PFC and help in its widespread adoption as an
      alternative to surgery.

PMID- 28440240
TI  - Cystic pancreatic lymphangioma diagnosed with endoscopic ultrasound-guided fine
      needle aspiration.
AB  - Pancreatic lymphangiomas are rare, but benign neoplasms. Historically, the
      diagnoses in various case reports were mostly made after surgical resection.
      There are emerging data concerning the utility of endoscopic ultrasound-guided
      fine needle aspiration (EUS-FNA) to differentiate it from more sinister
      pancreatic cystic neoplasms. A confident preoperative diagnosis with EUS-FNA is
      crucial to avoid unnecessary workup or surgery, especially for small and
      asymptomatic lesions. Here, we present a rare case of asymptomatic pancreatic
      lymphangioma which was diagnosed with EUS-FNA. The case highlights that a
      preoperative diagnosis of pancreatic lymphangioma can be made with certainty.

PMID- 28440241
TI  - Endoscopic ultrasound-guided choledochoduodenostomy for obstructive jaundice with
      venous collaterals around the bile duct wall (with video).

PMID- 28440243
TI  - A case of biliary fascioliasis mimicking a common bile duct tumor (with video).

PMID- 28440242
TI  - Esophageal adenocarcinoma metastasis in the left adrenal gland diagnosed by
      endoscopic ultrasound-guided fine needle aspiration.

PMID- 28440244
TI  - Looking back and looking forward: A satisfying journey.

PMID- 28440245
TI  - Pluripotent stem cells: A therapeutic source for age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) leads to progressive loss of central
      vision in the elderly. At a cellular level, there is aging of the retinal pigment
      epithelial (RPE) cells, and accumulation of lipofuscin that interferes with the
      proper functioning of RPE which eventually leads to apoptosis. Treatment depends
      on the stage of the disease. Wet AMD which has neovascularization is managed by
      local therapies such as laser photocoagulation and photodynamic therapy and is
      managed with injections of antivascular endothelial growth factor-based therapy.
      Unlike the wet AMD, an effective therapy does not exist for dry AMD and
      geographic atrophy. Cell replacement therapy has shown promise. This review
      discusses the opportunities in the various types of cell-based therapy, their
      limitations, and what is possible for India.

PMID- 28440246
TI  - What's new for us in strabismus?
AB  - Strabismus is one of the most challenging subspecialties encountered in the field
      of ophthalmology. The concept of etiology of strabismus is being advanced with
      the development of newer imaging modalities and increased understanding of the
      genetics of strabismus. Imaging is also being used to aid in the planning of
      strabismus surgery. Newer horizons are being explored in the amblyopia
      management. The good old eye-pad is being replaced with the iPad. Early detection
      of loss of stereopsis is being used to decide the timing for strabismus surgery.
      Improvement of binocular summation has been discovered as a benefit of corrective
      strabismus surgery. Newer surgical techniques such as new transposition
      procedures are being developed to correct complex strabismus. Strabismus
      surgeries aided by adjustable sutures have increased the precision of a
      strabismologist. A new light has been thrown on the psychosocial impact of
      strabismus. A present-day strabismologist has advanced from the goal of ocular
      alignment to a bigger perspective "to regain the paradise lost: stereopsis."

PMID- 28440247
TI  - Circulating biomarkers in glaucoma, age-related macular degeneration, and
      diabetic retinopathy.
AB  - Biomarkers to predict the altering physiological conditions over the period
      leading toward the ocular disorders are of major importance in therapeutics.
      Isolation and validation of the biomarkers specific to ocular diseases are a
      challenging task. Glaucoma is a neurodegenerative disease of the eye where the
      correlation of biomarkers in circulating fluid may be made specific for the eye.
      However, conditions such as wet age-related macular degeneration (AMD) and
      proliferative diabetic retinopathy (DR), circulating biomarkers might be having
      some degree of overlap with other conditions like cancer where a common factor
      such as angiogenesis is involved. Diabetes, a systemic disorder affecting the
      target organs such as eye, kidney, heart, and nervous system can be predicted
      using common circulating biomarkers. However, these markers need to be validated
      along with various stages of disease progression to enable the possibility of
      targeted pharmacological interventions apart from good glycemic control alone.
      This review compiles the attempts made to correlate such circulating biomarkers
      in the ocular conditions such as glaucoma, AMD, and DR in the search for a
      surrogate marker for diagnostic and prognostic value. To make biomarkers for the
      common convenience, genetic markers are excluded from this review.

PMID- 28440249
TI  - Innovations in pediatric cataract surgery.
AB  - Advances in technology have made surgery in children safer and faster. The
      management of pediatric cataract has made rapid progress in the past decade with
      the availability of safer anesthesia, newer technique's, more predictable
      intraocular lens (IOL) power calculation, a better understanding of neurobiology,
      genetics, amblyopia management, improved IOL designs for preventing visual axis
      opacification, and adjuvant postoperative care. Modern vitrectomy machines with
      minimally invasive instruments, radiofrequency, diathermy, and plasma blades help
      immensely in complicated cases. Preoperative evaluation with ultrasound
      biomicroscopy and optical coherence tomography (OCT) allows better planning of
      surgical procedure. The future holds good for stem cell research, customized OCT,
      and Zepto (precision pulse capsulotomy).

PMID- 28440250
TI  - Outcomes of deep anterior lamellar keratoplasty following autologous simple
      limbal epithelial transplant in pediatric unilateral severe chemical injury.
AB  - AIMS: To evaluate outcomes of deep anterior lamellar keratoplasty (DALK) in
      pediatric eyes with unilateral severe chemical injury which have undergone
      autologous simple limbal epithelial transplant (SLET). SETTINGS AND DESIGN: The
      study design was a retrospective case series. MATERIALS AND METHODS: This
      retrospective, case series of all children <16 years of age that have undergone
      DALK following autologous SLET procedure in unilateral severe chemical injury
      evaluates the outcomes and complications in the setting of a tertiary care center
      in North India. STATISTICAL ANALYSIS USED: Nonparametric data have been expressed
      as median (range), parametric qualitative data as percentage, and quantitative
      data as a mean +/- standard deviation. Spearman's correlation coefficient is used
      for finding a correlation between variables. RESULTS: Eleven eyes of 11 children
      (5 male and 6 female) with a mean age of 8.9 +/- 4.7 years underwent DALK
      following ocular surface reconstruction with autologous SLET earlier for
      unilateral severe chemical injury with limbal stem cell deficiency. Follow-up
      ranged from 6 to 18 months (13.00 +/- 4.58 months) following DALK procedure. All
      patients with a minimal follow-up of 6 months were evaluated for visual outcomes.
      Visual acuity ranged from 0.3 to 3 logMAR units (0.6 +/- 0.2 logMAR units).
      Complications were encountered in three patients. Anatomical success was seen in
      72.72% patients and visual success was noted in 54.54% patients. CONCLUSIONS:
      DALK is a feasible option in children with severe unilateral chemical injury who
      have undergone ocular surface reconstruction with autologous SLET procedures.

PMID- 28440248
TI  - Descemet stripping automated endothelial keratoplasty.
AB  - Endothelial keratoplasty is at present the gold standard for surgical treatment
      of corneal endothelial pathologies not associated with significant corneal scar.
      Tremendous progress has been made in recent years in improving the technology of
      endothelial keratoplasty techniques, such as descemet stripping automated
      endothelial keratoplasty (DSAEK) and descemet membrane endothelial keratoplasty.
      In this review, we discuss the current techniques and outcomes of DSAEK.

PMID- 28440251
TI  - Accommodative amplitude using the minus lens at different near distances.
AB  - PURPOSE: The purpose of this study was to compare the mean findings and the
      repeatability of the minus lens (ML) amplitude of accommodation (AA) at 33 cm and
      40 cm. MATERIALS AND METHODS: AA was measured from the dominant eye of 120 fully
      corrected subjects using the ML procedure when viewing the target at both 33 and
      40 cm. Each measurement was repeated between 24 and 48 hours after the first
      trial. RESULTS: Mean AA when tested at 33 cm and 40 cm was 10.20 diopter (D)
      (standard deviation [SD] =1.24) and 8.85 D (SD = 1.23), respectively (P < 0.001).
      The limits of agreement of the measured amplitude calculated with taking into
      account of the replicates at 33 and 40 cm were - 0.19 (95% confidence interval
      [CI]: -0.34 to -0.04) and 2.53 (95% CI: 2.38 to 2.68), respectively. The
      repeatability of testing at the two distances 33 and 40 cm was +/- 1.24 and +/-
      0.99, respectively. In addition, the retest reliability of measured amplitude
      using the intraclass correlation coefficient was 0.87 (95% CI: 0.789-0.920) at 33
      cm and 0.91 (95% CI: 0.872-0.945) at 40 cm. CONCLUSION: There is no agreement in
      the obtained amplitude at the two measurement distances. Testing the ML AA at 40
      cm may be superior given that a lower repeatability coefficient was observed.
      However, it is unclear whether the larger amplitude measured at 33 cm reflects a
      larger increase in accommodation (greater proximity effect) or a decrease in the
      ability to perceive the first slight sustained blur.

PMID- 28440252
TI  - Adjustment to acquired vision loss in adults presenting for visual disability
      certification.
AB  - CONTEXT: Rehabilitation of the visually disabled depends on how they adjust to
      loss; understanding contributing factors may help in effective rehabilitation.
      AIM: The aim of this study is to assess adjustment to acquired vision loss in
      adults. SETTINGS AND DESIGN: This observational study, conducted in the
      Department of Ophthalmology at a tertiary-level teaching hospital, included
      thirty persons (25-65 years) with <6/60 in the better eye, and vision loss since
      >=6-months. MATERIALS AND METHODS: Age, gender, rural/urban residence, education,
      current occupation, binocular distance vision, adjustment (Acceptance and Self
      Worth Adjustment Scale), depression (Center for Epidemiologic Studies-Depression
      Scale), social support (Duke Social Support and Stress Scale), and personality
      (10-item Personality Inventory scale) was recorded. STATISTICAL ANALYSIS: To
      determine their effect on adjustment, Student's t-test was used for categorical
      variables, Pearson's correlation for age, and Spearman's correlation for
      depression, personality trait and social support and stress. RESULTS: Of 30
      persons recruited, 24 were men (80%); 24 lived in urban areas (80%); 9 were
      employed (30%); and 14 (46.6%) had studied < Class 3. Adjustment was low (range:
      33%-60%; mean: 43.6 +/- 5.73). Reported support was low (median: 27.2;
      interquartile range [IQR]: 18.1-36.3); reported stress was low (median: 0.09;
      IQR: 0-18.1). Predominant personality traits (max score 14) were "Agreeableness"
      (average 12.0 +/- 1.68) and "Conscientiousness" (average 11.3 +/- 2.12).
      Emotional stability (average 9.2 +/- 2.53) was less prominent. Depression score
      ranged from 17 to 50 (average 31.6 +/- 6.01). The factors studied did not
      influence adjustment. CONCLUSIONS: Although adjustment did not vary with factors
      studied, all patients were depressed. Since perceived support and emotional
      stability was low, attention could be directed to support networks. Training
      patients in handling emotions, and training family members to respond to
      emotional needs of persons with visual disability, might contribute to reducing
      stress and depression.

PMID- 28440253
TI  - Evaluation of meibomian gland and tear film changes in patients with pterygium.
AB  - BACKGROUND: Recent studies have demonstrated that pterygium has a close
      relationship with dry eye disease. This study is to determine abnormalities in
      meibomian gland and tear function in patients with pterygium and to assess the
      relationship between the variables. MATERIALS AND METHODS: Forty eyes from forty
      patients with primary nasal pterygium and forty eyes from forty volunteers
      without ocular pathologies were enrolled in this study. Ocular surface disease
      index scores, meibomian gland expression scores, lid margin abnormality scores,
      meiboscore, tear film breakup time (BUT), Schirmer test (SIT) value, and the
      lower tear meniscus height (TMH), tear meniscus depth (TMD), and tear meniscus
      area (TMA) using Fourier domain optical coherence were performed. Analysis of
      variance was applied for intergroup comparisons. A statistical significance level
      of P < 0.05 was considered. RESULTS: Ocular symptom scores, BUT scores, lid
      margin abnormality, meibomian gland expression, and meiboscore were significantly
      higher in pterygium patients than in controls (P < 0.01 for all scores). However,
      the SIT scores, the lower TMH, TMD, and TMA values did not revealed a significant
      difference between two groups (all P > 0.05). Multivariate regression analysis
      demonstrated that meiboscore significantly correlated with ocular symptom scores,
      BUT, lid margin abnormality scores, and meibomian gland expression scores.
      CONCLUSIONS: Meibomian gland function may be altered in pterygium patients, which
      is associated with uncomfortable ocular symptoms. Being aware of meibomian gland
      changes seems essential to understand the complex relationship among pterygium,
      tear film functions, and ocular surface changes.

PMID- 28440254
TI  - Combined branch retinal vein and branch retinal artery occlusion - clinical
      features, systemic associations, and outcomes.
AB  - PURPOSE: Retinal vascular occlusions affecting both the arterial and venous
      systems are rare events. Combined branch retinal artery (BRAO) and vein (BRVO)
      occlusion are exceedingly rare and not well characterized. METHODS: Six patients
      with combined BRAO and BRVO underwent a comprehensive eye examination, fundus
      fluorescein angiography, optical coherence tomography, and cardiovascular
      evaluation. RESULTS: Mean age at presentation was 54 +/- 7.8 years (range: 39
      60), and five of the six were men. Patients had a combination of systemic
      comorbidities such as diabetes (5), hypertension (4), dyslipidemia (5), and
      hyperhomocysteinemia (1). All had unilateral combined occlusion characterized by
      narrowing and cattle tracking of blood in arteries and dilated tortuous veins in
      the involved quadrant. Fluorescein angiography demonstrated complete capillary
      drop out and a clear demarcation between the perfused and nonperfused retina.
      Presenting vision ranged from 6/9 to 1/60 Snellen's, and final vision depended on
      the macular perfusion status. All eyes were treated with angiography-guided
      sectoral laser photocoagulation, and three eyes required intravitreal bevacizumab
      due to macular edema or retinal neovascularization. CONCLUSIONS: Combined BRAO
      and BRVO is rare, may have unique underlying pathogenetic mechanisms, is
      associated with multiple systemic comorbidities and can yield good visual outcome
      if macula remains well perfused.

PMID- 28440255
TI  - Clinical profile and neuroimaging in pediatric optic neuritis in Indian
      population: A case series.
AB  - PURPOSE OF THE STUDY: The purpose of this study was to report clinical features,
      neuroimaging, and visual outcome in pediatric optic neuritis (ON) in Indian
      population. MATERIALS AND METHODS: This is a retrospective study of children up
      to the age of 16 years, diagnosed with ON, that presented at pediatric and
      neuroophthalmology clinic of a tertiary eye care center, in South India, within
      the period of 2010-2015. RESULTS: We identified 62 eyes of 40 children diagnosed
      as ON within the study period. The mean age was 11.15 +/- 3.24 years (1-15 years)
      with mean follow-up of 13 months. In this series, there was female preponderance
      (67%). Mean logarithm of the minimum angle of resolution visual acuity at
      presentation was 1.14 +/- 0.93, which after treatment recovered to 0.10 +/- 0.26
      at final visit (P < 0.001). Involvement was bilateral in 22 children (55%) and
      recurrent in 3 eyes of 3 children. Preceding febrile illness was reported in
      seven cases (18%). Four (10%) cases were diagnosed as multiple sclerosis (MS),
      one with neuromyelitis optica , and one with acute disseminated
      encephalomyelitis. One case was associated with tuberculous meningitis, 1 with
      septicemia, and 1 with bilateral maxillary sinusitis. Neuroimaging studies of
      optic nerve in 14 children demonstrated isolated optic nerve enhancement.
      Magnetic resonance imaging brain revealed white matter T2 hyperintense lesions
      separate from optic nerve in ten cases, of which four cases were diagnosed as MS.
      CONCLUSIONS: Bilateral presentation was common, association with MS was low.
      Papillitis was more frequent than retrobulbar neuritis and prognosis was good in
      pediatric ON in Indian population.

PMID- 28440256
TI  - Bilateral internuclear ophthalmoplegia following head trauma.

PMID- 28440257
TI  - Managing multiple caterpillar hair in the eye.
AB  - Ophthalmia nodosa with vitreoretinal involvement is rare and may cause permanent
      loss of eye due to persistent inflammation of the eye. A young female patient
      having multiple caterpillar hair in the eye including cornea, anterior chamber,
      sclera, and pars plana presented with recurrent vitritis and pars planitis.
      Ultrasound biomicroscopy played a vital role and helped in localizing the hair
      embedded in the pars plana region which were managed by pars plana vitrectomy
      leading to complete recovery.

PMID- 28440258
TI  - Neuroretinitis as presenting and the only presentation of Lyme disease: Diagnosis
      and management.
AB  - We present a case of neuroretinitis as presenting and the only presentation of
      Lyme disease in a 25-year-old female who visited hilly areas in the Himalayas of
      North India. She presented with right eye sudden and painless blurring of vision.
      Her vision at presentation was 20/60. She had fundus examination; fundus
      fluorescein angiography (FFA) and optical coherence tomography (OCT) imaging
      showed classical features of neuroretinitis. No other organ was involved. Oral
      steroids were prescribed and relevant investigations sent for noninfective and
      infective causes. Worsened visual acuity (VA) to hand movement and positive IgM
      titers for Borrelia burgdorferi led to the diagnosis of Lyme disease-associated
      neuroretinitis. Treatment with oral doxycycline plus oral steroids for 4 weeks
      revealed VA of 20/20 and resolution of fundus and OCT changes. Neuroretinitis as
      presenting and the only presentation of Lyme disease will be discussed with
      serial fundus, FFA, and OCT pictures.

PMID- 28440259
TI  - Persistent unilateral nictitating membrane in a 9-year-old girl: A rare case
      report.
AB  - We report a case of persisting nictitating membrane in a 9-year-old girl
      presenting to us with the complaints of fleshy mass in the medial part of the
      left eye since birth, which was nonprogressive. On examination, her left eye was
      amblyopic with a vision of 20/500. The membrane was continuous with the medial
      canthus and was spread in a horizontal fashion, covering the underlying bulbar
      conjunctiva and one-third of the cornea. The globe however moved freely
      underneath the membrane, indicating no attachment between the globe and overlying
      membrane. The patient underwent simple excision of the nictitating membrane with
      good outcome.

PMID- 28440260
TI  - Immortal Ozurdex: A 10-month follow-up of an intralenticular implant.
AB  - A 78-year-old male who had received a dexamethasone implant (Ozurdex, Allergan,
      Inc., Irvine, CA, USA) 15 days back for recalcitrant diabetic macular edema in
      the left eye came to us for a second opinion. On examination, his corrected
      distance visual acuity was 20/20 in the right eye and 20/40 in the left eye.
      Early cataractous changes were present in both eyes. The intraocular pressure was
      within normal limits. The Ozurdex implant was seen lodged in the posterior cortex
      of the crystalline lens in the left eye, confirmed on anterior segment optical
      coherence tomography (OCT) and ultrasound biomicroscopy. Fundus examination
      showed moderate nonproliferative diabetic retinopathy in both eyes with macular
      edema and epiretinal membrane in the left eye, confirmed on OCT. The patient was
      noncompliant and returned after 10 months. Interestingly, the implant was still
      present in the same location with the same vision and anterior segment findings
      as before. The OCT showed a reduction in macular edema. The patient was advised
      regular follow-up and cataract surgery at a later date.

PMID- 28440261
TI  - Clinical profile of amblyopia in a tertiary care teaching hospital in Southern
      India.

PMID- 28440262
TI  - Risk of complications and urinary incontinence following cytoreductive
      prostatectomy: a multi-institutional study.
AB  - Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows
      superior oncologic control when compared to current standard of care androgen
      deprivation therapy alone. However, the safety and benefit of cytoreduction in
      metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated
      the incidence of complications following CRP in men newly diagnosed with mPCa. A
      total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary
      surgical centers were compared to 598 men who underwent radical prostatectomy for
      clinically localized prostate cancer (PCa). Urinary incontinence was defined as
      the use of any pad. CRP had longer operative times (200 min vs 140 min, P <
      0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared
      to the control group. However, both overall (8.82% vs 5.85%) and major
      complication rates (4.41% vs 2.17%) were comparable between the two groups.
      Importantly, urinary incontinence rate at 1-year after surgery was significantly
      higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic
      analysis showed that the estimated blood loss was the only independent predictor
      of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI:
      1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01
      1.36; P = 0.034). In conclusion, CRP is more challenging than radical
      prostatectomy and associated with a notably higher incidence of urinary
      incontinence. Nevertheless, CRP is a technically feasible and safe surgery for
      selecting PCa patients who present with node-positive or bony metastasis when
      performed by experienced surgeons. A prospective, multi-institutional clinical
      trial is currently underway to verify this concept.

PMID- 28440263
TI  - Suprapubic cystostomy versus nonsuprapubic cystostomy during monopolar
      transurethral resection of prostate: a propensity score-matched analysis.
AB  - We aim to reassess the safety of the monopolar transurethral resection of the
      prostate (M-TURP) without suprapubic cystostomy at our institution over the past
      decade. This retrospective study was conducted in patients who underwent M-TURP
      at Peking University First Hospital between 2003 and 2013. A total of 1680
      patients who had undergone M-TURP were identified, including 539 patients in the
      noncystostomy group and 1141 patients in the cystostomy group. After propensity
      score matching, the number of patients in each group was 456. Smaller reductions
      in hemoglobin and hematocrit (10.9 g vs 17.6 g and 3.6% vs 4.7%, respectively)
      were found in the noncystostomy group. In addition, patients undergoing surgery
      without cystostomy had their catheters removed earlier (4.6 days vs 5.2 days),
      required shorter postoperative stays in the hospital (5.1 days vs 6.0 days), and
      were at lower risk of operative complications (5.7% vs 9.2%), especially bleeding
      requiring blood transfusion (2.9% vs 6.1%). Similar findings were observed in
      cohorts of prostates of 30-80 ml and prostates >80 ml. Furthermore, among
      patients with a resection weight >42.5 g or surgical time >90 min, or even
      propensity-matched patients based on surgical time, those with cystostomy seemed
      to be at a higher risk of operative complications. These results suggest that M
      TURP without suprapubic cystostomy is a safe and effective method, even among
      patients with larger prostates, heavier estimated resection weights, and longer
      surgical times.

PMID- 28440264
TI  - Use of testicular sperm for intracytoplasmic sperm injection in men with high
      sperm DNA fragmentation: a SWOT analysis.
AB  - Spermatozoa retrieved from the testis of men with high levels of sperm DNA
      fragmentation (SDF) in the neat semen tend to have better DNA quality. Given the
      negative impact of SDF on the outcomes of Assisted Reproductive Technology (ART),
      an increased interest has emerged about the use of testicular sperm for
      intracytoplasmic sperm injection (Testi-ICSI). In this article, we used a SWOT
      (strengths, weaknesses, opportunities, and threats) analysis to summarize the
      advantages and drawbacks of this intervention. The rationale of Testi-ICSI is
      bypass posttesticular DNA fragmentation caused by oxidative stress during sperm
      transit through the epididymis. Hence, oocyte fertilization by genomically intact
      testicular spermatozoa may be optimized, thus increasing the chances of creating
      a normal embryonic genome and the likelihood of achieving a live birth, as
      recently demonstrated in men with high SDF. However, there is still limited
      evidence as regards the clinical efficacy of Testi-ICSI, thus creating
      opportunities for further confirmatory clinical research as well as investigation
      of Testi-ICSI in clinical scenarios other than high SDF. Furthermore, Testi-ICSI
      can be compared to other laboratory preparation methods for deselecting sperm
      with damaged DNA. At present, the available literature supports the use of
      testicular sperm when performing ICSI in infertile couples whose male partners
      have posttesticular SDF. Due to inherent risks of sperm retrieval, Testi-ICSI
      should be offered when less invasive treatments for alleviating DNA damage have
      failed. A call for continuous monitoring is nonetheless required concerning the
      health of generated offspring and the potential complications of sperm retrieval.

PMID- 28440265
TI  - Role of Jun amino-terminal kinase (JNK) in apoptosis of cavernosal tissue during
      acute phase after cavernosal nerve injury.
AB  - The present study aimed to identify which mitogen-activated protein kinase (p38
      or Jun amino-terminal kinase [JNK]) was involved in cavernosal apoptosis during
      the acute phase after cavernosal nerve crush injury (CNCI) in rats to ameliorate
      apoptosis of cavernosal tissue, such as smooth muscle (SM). A total of twenty 10
      week-old male Sprague-Dawley rats were divided equally into two groups: sham
      surgery (S) and CNCI (I). The I group approximated the clinical situation of men
      undergoing radical prostatectomy using two 60-second compressions of both CNs
      with a microsurgical vascular clamp. At 2-week postinjury, erectile response was
      assessed using electrostimulation. Penile tissues were harvested for
      immunohistochemistry analysis of alpha-SM actin (alpha-SMA), western blot
      analysis, and double immunofluorescence analysis of alpha-SMA and phosphorylated
      p38 or JNK, as well as double immunofluorescent of TUNEL and phosphorylated p38
      or JNK. At 2-week postinjury, the I group had a significantly lower
      intracavernous pressure (ICP)/mean arterial pressure (MAP) and a lower area under
      the curve (AUC)/MAP than the S group. The I group also exhibited decreased
      immunohistochemical staining of alpha-SMA, an increase in the number of SM cells
      positive for phosphorylated JNK, an increased number of apoptotic cells positive
      for phosphorylated JNK, and increased JNK phosphorylation compared with the S
      group. However, there was no significant difference in p38 phosphorylation
      expression or the number of SM cells positive for phosphorylated p38 between the
      two groups. In conclusion, our data suggest that JNK, not p38, is involved in
      cavernosal apoptosis during the acute phase after partial CN damage.

PMID- 28440266
TI  - Prof. K. Siddappa (1931-2017).

PMID- 28440267
TI  - Erratum: Digital volumetric measurement of cutaneous leishmaniasis lesions: Blur
      estimation method.
AB  - [This corrects the article DOI: 10.4103/ijdvl.IJDVL_134_16.].

PMID- 28440268
TI  - Erratum: Clinical characteristics of acquired ungual fibrokeratoma.
AB  - [This corrects the article DOI: 10.4103/0378-6323.193611.].

PMID- 28440269
TI  - Ruthenium-cobalt nanoalloys encapsulated in nitrogen-doped graphene as active
      electrocatalysts for producing hydrogen in alkaline media.
AB  - The scalable production of hydrogen could conveniently be realized by alkaline
      water electrolysis. Currently, the major challenge confronting hydrogen evolution
      reaction (HER) is lacking inexpensive alternatives to platinum-based
      electrocatalysts. Here we report a high-efficient and stable electrocatalyst
      composed of ruthenium and cobalt bimetallic nanoalloy encapsulated in nitrogen
      doped graphene layers. The catalysts display remarkable performance with low
      overpotentials of only 28 and 218 mV at 10 and 100 mA cm-2, respectively, and
      excellent stability of 10,000 cycles. Ruthenium is the cheapest platinum-group
      metal and its amount in the catalyst is only 3.58 wt.%, showing the catalyst high
      activity at a very competitive price. Density functional theory calculations
      reveal that the introduction of ruthenium atoms into cobalt core can improve the
      efficiency of electron transfer from alloy core to graphene shell, beneficial for
      enhancing carbon-hydrogen bond, thereby lowing DeltaGH* of HER.

PMID- 28440270
TI  - Refined genetic maps reveal sexual dimorphism in human meiotic recombination at
      multiple scales.
AB  - In humans, males have lower recombination rates than females over the majority of
      the genome, but the opposite is usually true near the telomeres. These broad
      scale differences have been known for decades, yet little is known about
      differences at the fine scale. By combining data sets, we have collected
      recombination events from over 100,000 meioses and have constructed sex-specific
      genetic maps at a previously unachievable resolution. Here we show that, although
      a substantial fraction of the genome shows some degree of sexually dimorphic
      recombination, the vast majority of hotspots are shared between the sexes, with
      only a small number of putative sex-specific hotspots. Wavelet analysis indicates
      that most of the differences can be attributed to the fine scale, and that
      variation in rate between the sexes can mostly be explained by differences in
      hotspot magnitude, rather than location. Nonetheless, known recombination
      associated genomic features, such as THE1B repeat elements, show systematic
      differences between the sexes.

PMID- 28440271
TI  - Two-dimensional Mo1.33C MXene with divacancy ordering prepared from parent 3D
      laminate with in-plane chemical ordering.
AB  - The exploration of two-dimensional solids is an active area of materials
      discovery. Research in this area has given us structures spanning graphene to
      dichalcogenides, and more recently 2D transition metal carbides (MXenes). One of
      the challenges now is to master ordering within the atomic sheets. Herein, we
      present a top-down, high-yield, facile route for the controlled introduction of
      ordered divacancies in MXenes. By designing a parent 3D atomic laminate,
      (Mo2/3Sc1/3)2AlC, with in-plane chemical ordering, and by selectively etching the
      Al and Sc atoms, we show evidence for 2D Mo1.33C sheets with ordered metal
      divacancies and high electrical conductivities. At ~1,100 F cm-3, this 2D
      material exhibits a 65% higher volumetric capacitance than its counterpart, Mo2C,
      with no vacancies, and one of the highest volumetric capacitance values ever
      reported, to the best of our knowledge. This structural design on the atomic
      scale may alter and expand the concept of property-tailoring of 2D materials.

PMID- 28440272
TI  - Corrigendum: Pharmacological inhibition of adipose triglyceride lipase corrects
      high-fat diet-induced insulin resistance and hepatosteatosis in mice.

PMID- 28440273
TI  - Active matter logic for autonomous microfluidics.
AB  - Chemically or optically powered active matter plays an increasingly important
      role in materials design, but its computational potential has yet to be explored
      systematically. The competition between energy consumption and dissipation
      imposes stringent physical constraints on the information transport in active
      flow networks, facilitating global optimization strategies that are not well
      understood. Here, we combine insights from recent microbial experiments with
      concepts from lattice-field theory and non-equilibrium statistical mechanics to
      introduce a generic theoretical framework for active matter logic. Highlighting
      conceptual differences with classical and quantum computation, we demonstrate how
      the inherent non-locality of incompressible active flow networks can be utilized
      to construct universal logical operations, Fredkin gates and memory storage in
      set-reset latches through the synchronized self-organization of many individual
      network components. Our work lays the conceptual foundation for developing
      autonomous microfluidic transport devices driven by bacterial fluids, active
      liquid crystals or chemically engineered motile colloids.

PMID- 28440274
TI  - Reply to 'Questioning antiviral RNAi in mammals'.

PMID- 28440275
TI  - Antimicrobials: Expressing antibiotic gene clusters.

PMID- 28440276
TI  - Next-generation probiotics: the spectrum from probiotics to live biotherapeutics.
AB  - The leading probiotics currently available to consumers are generally drawn from
      a narrow range of organisms. Knowledge of the gut microbiota and its constituent
      actors is changing this paradigm, particularly given the phylogenetic range and
      relatively unknown characteristics of the organisms under investigation as novel
      therapeutics. For this reason, and because their development is likely to be more
      amenable to a pharmaceutical than a food delivery route, these organisms are
      often operationally referred to as next-generation probiotics, a concept that
      overlaps with the emerging concept of live biotherapeutic products. The latter is
      a class of organisms developed exclusively for pharmaceutical application. In
      this Perspective, we discuss what lessons have been learned from working with
      traditional probiotics, explore the kinds of organisms that are likely to be used
      as novel microbial therapeutics, discuss the regulatory framework required, and
      propose how scientists may meet this challenge.

PMID- 28440277
TI  - Questioning antiviral RNAi in mammals.

PMID- 28440279
TI  - The geometric phase of Zn- and T-symmetric nanomagnets as a classification
      toolkit.
AB  - We derive the general form of the non-trivial geometric phase resulting from the
      unique combination of point group and time reversal symmetries. This phase arises
      e.g. when a magnetic adatom is adsorbed on a non-magnetic Cn crystal surface,
      where n denotes the fold of the principal axis. The energetic ordering and the
      relevant quantum numbers of the eigenstates are entirely determined by this
      quantity. Moreover, this phase allows to conveniently predict the protection
      mechanism of any prepared state, shedding light onto a large number of
      experiments and allowing a classification scheme. Owing to its robustness this
      geometric phase also has great relevance for a large number of applications in
      quantum computing, where topologically protected states bearing long relaxation
      times are highly desired.

PMID- 28440278
TI  - An insider's perspective: Bacteroides as a window into the microbiome.
AB  - Over the last decade, our appreciation for the contribution of resident gut
      microorganisms-the gut microbiota-to human health has surged. However, progress
      is limited by the sheer diversity and complexity of these microbial communities.
      Compounding the challenge, the majority of our commensal microorganisms are not
      close relatives of Escherichia coli or other model organisms and have eluded
      culturing and manipulation in the laboratory. In this Review, we discuss how over
      a century of study of the readily cultured, genetically tractable human gut
      Bacteroides has revealed important insights into the biochemistry, genomics and
      ecology that make a gut bacterium a gut bacterium. While genome and metagenome
      sequences are being produced at breakneck speed, the Bacteroides provide a
      significant 'jump-start' on uncovering the guiding principles that govern
      microbiota-host and inter-bacterial associations in the gut that will probably
      extend to many other members of this ecosystem.

PMID- 28440280
TI  - Targeting ASIC3 for Relieving Mice Fibromyalgia Pain: Roles of
      Electroacupuncture, Opioid, and Adenosine.
AB  - Many scientists are seeking better therapies for treating fibromyalgia (FM) pain.
      We used a mouse model of FM to determine if ASIC3 and its relevant signaling
      pathway participated in FM pain. We demonstrated that FM-induced mechanical
      hyperalgesia was attenuated by electroacupuncture (EA). The decrease in fatigue
      induced lower motor function in FM mice was also reversed by EA. These EA-based
      effects were abolished by the opioid receptor antagonist naloxone and the
      adenosine A1 receptor antagonist rolofylline. Administration of opioid receptor
      agonist endomorphin (EM) or adenosine A1 receptor agonist N6-cyclopentyladenosine
      (CPA) has similar results to EA. Similar results were also observed in ASIC3-/-
      or ASIC3 antagonist (APETx2) injected mice. Using western blotting, we determined
      that pPKA, pPI3K, and pERK were increased during a dual acidic injection priming
      period. Nociceptive receptors, such as ASIC3, Nav1.7, and Nav1.8, were
      upregulated in the dorsal root ganglion (DRG) and spinal cord (SC) of FM mice.
      Furthermore, pPKA, pPI3K, and pERK were increased in the central thalamus. These
      aforementioned mechanisms were completely abolished in ASIC3 knockout mice.
      Electrophysiological results also indicated that acid potentiated Nav currents
      through ASIC3 and ERK pathway. Our results highlight the crucial role of ASIC3
      mediated mechanisms in the treatment of FM-induced mechanical hyperalgesia.

PMID- 28440281
TI  - Short channel effects on electrokinetic energy conversion in solid-state
      nanopores.
AB  - The ion selectivity of nanopores due to the wall surface charges is capable of
      inducing strong coupling between fluidic and ionic motion within the system. This
      interaction opens up the prospect of operating nanopores as nanoscale devices for
      electrokinetic energy conversion. However, the very short channel lengths make
      the ionic movement and fluidics inside the pore to be substantially affected by
      the ion depletion/accumulation around the pore ends. Based on three-dimensional
      electrokinetic modeling and simulation, we present a systematic theoretical study
      of nanopore electrical resistance, fluidic impedance, and streaming conductance.
      Our results show that by utilizing the short channel effect and preparing
      slippery nanopores the energy conversion efficiency can be dramatically increased
      to about 9% under large salt concentrations.

PMID- 28440282
TI  - Understanding the Rising Phase of the PM2.5 Concentration Evolution in Large
      China Cities.
AB  - Long-term air quality observations are seldom analyzed from a dynamic view. This
      study analyzed fine particulate matter (PM2.5) pollution processes using long
      term PM2.5 observations in three Chinese cities. Pollution processes were defined
      as linearly growing PM2.5 concentrations following the criteria of coefficient of
      determination R2 > 0.8 and duration time T >= 18 hrs. The linear slopes
      quantitatively measured pollution levels by PM2.5 concentrations rising rates
      (PMRR, MUg/(m3.hr)). The 741, 210 and 193 pollution processes were filtered out,
      respectively, in Beijing (BJ), Shanghai (SH), and Guangzhou (GZ). Then the
      relationships between PMRR and wind speed, wind direction, 24-hr backward points,
      gaseous pollutants (CO, NO2 and SO2) concentrations, and regional PM2.5 levels
      were studied. Inverse relationships existed between PMRR and wind speed. The wind
      directions and 24-hr backward points converged in specific directions indicating
      long-range transport. Gaseous pollutants concentrations increased at variable
      rates in the three cities with growing PMRR values. PM2.5 levels at the upwind
      regions of BJ and SH increased at high PMRRs. Regional transport dominated the
      PM2.5 pollution processes of SH. In BJ, both local contributions and regional
      transport increased during high-PMRR pollution processes. In GZ, PM2.5 pollution
      processes were mainly caused by local emissions.

PMID- 28440283
TI  - Quantitative diagnosis of breast tumors by morphometric classification of
      microenvironmental myoepithelial cells using a machine learning approach.
AB  - Machine learning systems have recently received increased attention for their
      broad applications in several fields. In this study, we show for the first time
      that histological types of breast tumors can be classified using subtle
      morphological differences of microenvironmental myoepithelial cell nuclei without
      any direct information about neoplastic tumor cells. We quantitatively measured
      11661 nuclei on the four histological types: normal cases, usual ductal
      hyperplasia and low/high grade ductal carcinoma in situ (DCIS). Using a machine
      learning system, we succeeded in classifying the four histological types with
      90.9% accuracy. Electron microscopy observations suggested that the activity of
      typical myoepithelial cells in DCIS was lowered. Through these observations as
      well as meta-analytic database analyses, we developed a paracrine cross-talk
      based biological mechanism of DCIS progressing to invasive cancer. Our
      observations support novel approaches in clinical computational diagnostics as
      well as in therapy development against progression.

PMID- 28440284
TI  - CYP2J2 and Its Metabolites EETs Attenuate Insulin Resistance via Regulating
      Macrophage Polarization in Adipose Tissue.
AB  - Macrophages in adipose tissue are associated with obesity-induced low-grade
      inflammation, which contributed to insulin resistance and the related metabolic
      diseases. Previous studies demonstrated the beneficial effects of
      epoxyeicosatrienoic acids (EETs) on metabolic disorders and inflammation. Here we
      investigated the effects of CYP2J2-EETs-sEH metabolic pathway on insulin
      resistance in mice and the potential mechanisms. High fat diet (HFD)-induced
      obesity caused metabolic dysfunction with more weight gain, elevated glucose and
      lipids levels, impaired glucose tolerance and insulin sensitivity, while increase
      in EETs level by rAAV-mediated CYP2J2 overexpression, administration of sEH
      inhibit TUPS or EETs infusion significantly attenuated these metabolic disorders.
      EETs inhibited macrophages recruitment to adipose tissue and their switch to
      classically activated macrophage (M1) phenotype, while preserved the
      alternatively activated macrophage (M2) phenotype, which was accompanied by
      substantially reduced adipose tissue and systemic inflammation and insulin
      resistance. In vitro studies further clarified the effects of EETs on macrophage
      infiltration and polarization, and microarray assays showed that cAMP-EPAC
      signaling pathway was involved in these processes. Collectively, these results
      described key beneficial immune-regulatory properties and metabolic regulation of
      CYP2J2-EETs-sEH metabolic pathway, and indicated therapeutic potential of EETs in
      obesity-induced insulin resistance and related inflammatory diseases through
      modulating macrophage polarization targeting cAMP-EPAC signaling pathway.

PMID- 28440285
TI  - Ionizing radiation abrogates the pro-tumorigenic capacity of cancer-associated
      fibroblasts co-implanted in xenografts.
AB  - Cancer-associated fibroblasts (CAFs) are abundantly present in solid tumors and
      affect tumorigenesis and therapeutic responses. In the context of clinical
      radiotherapy, the impact of irradiated CAFs to treatment outcomes is largely
      unexplored. Aiming at improving radiotherapy efficacy, we have here explored the
      effect of radiation on the inherent pro-tumorigenic capacity of CAFs in animals.
      Ionizing radiation was delivered to cultured CAFs as single-high or fractionated
      doses. Tumor development was compared in mice receiving A549 lung tumor cells
      admixed with irradiated or control CAFs. Biological mechanisms behind tumor
      growth regulation were investigated by quantitative histology and
      immunohistochemistry. Viability assessments confirmed that irradiated CAFs are
      fully functional prior to implantation. However, the enhanced tumorigenic effect
      observed in tumors co-implanted with control CAFs was abrogated in tumors
      established with irradiated CAFs. Experiments to ascertain fate of implanted
      fibroblasts showed that exogenously administered CAFs reside at the implantation
      site for few days, suggesting that tumor growth regulation from admixed CAFs take
      place during initial tumor formation. Our work demonstrate that irradiated CAFs
      lose their pro-tumorigenic potential in vivo, affecting angiogenesis and tumor
      engraftment. This finding propose a previously unknown advantageous effect
      induced by radiotherapy, adding to the direct cytotoxic effects on transformed
      epithelial cells.

PMID- 28440286
TI  - Size and shape variations of the bony components of sperm whale cochleae.
AB  - Several mass strandings of sperm whales occurred in the North Sea during January
      and February 2016. Twelve animals were necropsied and sampled around 48 h after
      their discovery on German coasts of Schleswig Holstein. The present study aims to
      explore the morphological variation of the primary sensory organ of sperm whales,
      the left and right auditory system, using high-resolution computerised tomography
      imaging. We performed a quantitative analysis of size and shape of cochleae using
      landmark-based geometric morphometrics to reveal inter-individual anatomical
      variations. A hierarchical cluster analysis based on thirty-one external
      morphometric characters classified these 12 individuals in two stranding
      clusters. A relative amount of shape variation could be attributable to
      geographical differences among stranding locations and clusters. Our geometric
      data allowed the discrimination of distinct bachelor schools among sperm whales
      that stranded on German coasts. We argue that the cochleae are individually
      shaped, varying greatly in dimensions and that the intra-specific variation
      observed in the morphology of the cochleae may partially reflect their
      affiliation to their bachelor school. There are increasing concerns about the
      impact of noise on cetaceans and describing the auditory periphery of odontocetes
      is a key conservation issue to further assess the effect of noise pollution.

PMID- 28440287
TI  - Sorption of Nickel(II) on a Calcareous Aridisol Soil, China: Batch, XPS, and
      EXAFS Spectroscopic Investigations.
AB  - The sorption of Ni(II) on a calcareous aridisol (CA) soil, one of the major soil
      types in northwestern China, was investigated using batch and extended X-ray
      absorption fine structure (EXAFS) approaches in a 0.01 mol/L NaClO4 solution at
      different pH values (6.0-10.0), temperatures (25-60  degrees C) and contact times
      (2-15 days). Under alkaline conditions, EXAFS analysis showed that the
      interatomic distances between Ni and O atoms (RNi-O) were approximately 2.04 A
      with a typical coordination number (CN) of ~6.0 O atoms in the contact time range
      from 2 to 15 days. The RNi-Ni (~3.07 A) suggested that the structure of the
      Ni(II) adsorbed on the CA soil was basically the same as that of Ni(OH)2(s),
      while the Ni-Al shell (RNi-Al ~3.16 A) gradually formed and grew with the
      increasing contact time. Under weakly acidic conditions, the sorption mechanism
      of Ni(II) on the CA soil possibly included at least two processes: (i) a fast
      accumulation dominated by ion exchange and surface complexation and (ii) the
      formation of a Ni-Al LDH phase over the long term. A high temperature is
      beneficial to the fixation of Ni(II) on the CA soil and the formation of a Ni-Al
      LDH.

PMID- 28440288
TI  - Longitudinal spin Seebeck coefficient: heat flux vs. temperature difference
      method.
AB  - The determination of the longitudinal spin Seebeck effect (LSSE) coefficient is
      currently plagued by a large uncertainty due to the poor reproducibility of the
      experimental conditions used in its measurement. In this work we present a
      detailed analysis of two different methods used for the determination of the LSSE
      coefficient. We have performed LSSE experiments in different laboratories, by
      using different setups and employing both the temperature difference method and
      the heat flux method. We found that the lack of reproducibility can be mainly
      attributed to the thermal contact resistance between the sample and the thermal
      baths which generate the temperature gradient. Due to the variation of the
      thermal resistance, we found that the scaling of the LSSE voltage to the heat
      flux through the sample rather than to the temperature difference across the
      sample greatly reduces the uncertainty. The characteristics of a single YIG/Pt
      LSSE device obtained with two different setups was (1.143 +/- 0.007) 10-7 Vm/W
      and (1.101 +/- 0.015) 10-7 Vm/W with the heat flux method and (2.313 +/- 0.017)
      10-7 V/K and (4.956 +/- 0.005) 10-7 V/K with the temperature difference method.
      This shows that systematic errors can be considerably reduced with the heat flux
      method.

PMID- 28440289
TI  - Toward surface orbitronics: giant orbital magnetism from the orbital Rashba
      effect at the surface of sp-metals.
AB  - As the inversion symmetry is broken at a surface, spin-orbit interaction gives
      rise to spin-dependent energy shifts - a phenomenon which is known as the spin
      Rashba effect. Recently, it has been recognized that an orbital counterpart of
      the spin Rashba effect - the orbital Rashba effect - can be realized at surfaces
      even without spin-orbit coupling. Here, we propose a mechanism for the orbital
      Rashba effect based on sp orbital hybridization, which ultimately leads to the
      electric polarization of surface states. For the experimentally well-studied
      system of a BiAg2 monolayer, as a proof of principle, we show from first
      principles that this effect leads to chiral orbital textures in k-space. In
      predicting the magnitude of the orbital moment arising from the orbital Rashba
      effect, we demonstrate the crucial role played by the Berry phase theory for the
      magnitude and variation of the orbital textures. As a result, we predict a
      pronounced manifestation of various orbital effects at surfaces, and proclaim the
      orbital Rashba effect to be a key platform for surface orbitronics.

PMID- 28440290
TI  - Counter resistance.

PMID- 28440291
TI  - Identifying N6-methyladenosine sites using multi-interval nucleotide pair
      position specificity and support vector machine.
AB  - N6-methyladenosine (m6A) refers to methylation of the adenosine nucleotide acid
      at the nitrogen-6 position. It plays an important role in a series of biological
      processes, such as splicing events, mRNA exporting, nascent mRNA synthesis,
      nuclear translocation and translation process. Numerous experiments have been
      done to successfully characterize m6A sites within sequences since high
      resolution mapping of m6A sites was established. However, as the explosive growth
      of genomic sequences, using experimental methods to identify m6A sites are time
      consuming and expensive. Thus, it is highly desirable to develop fast and
      accurate computational identification methods. In this study, we propose a
      sequence-based predictor called RAM-NPPS for identifying m6A sites within RNA
      sequences, in which we present a novel feature representation algorithm based on
      multi-interval nucleotide pair position specificity, and use support vector
      machine classifier to construct the prediction model. Comparison results show
      that our proposed method outperforms the state-of-the-art predictors on three
      benchmark datasets across the three species, indicating the effectiveness and
      robustness of our method. Moreover, an online webserver implementing the proposed
      predictor has been established at http://server.malab.cn/RAM-NPPS/. It is
      anticipated to be a useful prediction tool to assist biologists to reveal the
      mechanisms of m6A site functions.

PMID- 28440292
TI  - Visible light guided manipulation of liquid wettability on photoresponsive
      surfaces.
AB  - Photoresponsive titania surfaces are of great interest due to their unique
      wettability change upon ultraviolet light illumination. However, their
      applications are often limited either by the inability to respond to visible
      light or the need for special treatment to recover the original wettability.
      Sensitizing TiO2 surfaces with visible light-absorbing materials has been
      utilized in photovoltaic applications. Here we demonstrate that a dye-sensitized
      TiO2 surface can selectively change the wettability towards contacting liquids
      upon visible light illumination due to a photo-induced voltage across the liquid
      and the underlying surface. The photo-induced wettability change of our surfaces
      enables external manipulation of liquid droplet motion upon illumination. We show
      demulsification of surfactant-stabilized brine-in-oil emulsions via coalescence
      of brine droplets on our dye-sensitized TiO2 surface upon visible light
      illumination. We anticipate that our surfaces will have a wide range of
      applications including microfluidic devices with customizable wettability, solar
      driven oil-water clean-up and demulsification technologies.

PMID- 28440293
TI  - Exploiting induced pluripotent stem cell-derived macrophages to unravel host
      factors influencing Chlamydia trachomatis pathogenesis.
AB  - Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted
      infections and preventable blindness worldwide. There are, however, limited in
      vitro models to study the role of host genetics in the response of macrophages to
      this obligate human pathogen. Here, we describe an approach using macrophages
      derived from human induced pluripotent stem cells (iPSdMs) to study macrophage
      Chlamydia interactions in vitro. We show that iPSdMs support the full infectious
      life cycle of C. trachomatis in a manner that mimics the infection of human blood
      derived macrophages. Transcriptomic and proteomic profiling of the macrophage
      response to chlamydial infection highlighted the role of the type I interferon
      and interleukin 10-mediated responses. Using CRISPR/Cas9 technology, we generated
      biallelic knockout mutations in host genes encoding IRF5 and IL-10RA in iPSCs,
      and confirmed their roles in limiting chlamydial infection in macrophages. This
      model can potentially be extended to other pathogens and tissue systems to
      advance our understanding of host-pathogen interactions and the role of human
      genetics in influencing the outcome of infections.

PMID- 28440294
TI  - Next-generation DNA sequencing identifies novel gene variants and pathways
      involved in specific language impairment.
AB  - A significant proportion of children have unexplained problems acquiring
      proficient linguistic skills despite adequate intelligence and opportunity.
      Developmental language disorders are highly heritable with substantial societal
      impact. Molecular studies have begun to identify candidate loci, but much of the
      underlying genetic architecture remains undetermined. We performed whole-exome
      sequencing of 43 unrelated probands affected by severe specific language
      impairment, followed by independent validations with Sanger sequencing, and
      analyses of segregation patterns in parents and siblings, to shed new light on
      aetiology. By first focusing on a pre-defined set of known candidates from the
      literature, we identified potentially pathogenic variants in genes already
      implicated in diverse language-related syndromes, including ERC1, GRIN2A, and
      SRPX2. Complementary analyses suggested novel putative candidates carrying
      validated variants which were predicted to have functional effects, such as OXR1,
      SCN9A and KMT2D. We also searched for potential "multiple-hit" cases; one proband
      carried a rare AUTS2 variant in combination with a rare inherited haplotype
      affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D
      together with a rare stop-gain in SYNPR. On broadening scope to all rare and
      novel variants throughout the exomes, we identified biological themes that were
      enriched for such variants, including microtubule transport and cytoskeletal
      regulation.

PMID- 28440295
TI  - KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer
      stem cells through Wnt/beta-catenin signalling.
AB  - Human colorectal cancer stem cells (CSCs) are tumour initiating cells that can
      self-renew and are highly tumorigenic and chemoresistant. While genetic mutations
      associated with human colorectal cancer development are well-known, little is
      known about how and whether epigenetic factors specifically contribute to the
      functional properties of human colorectal CSCs. Here we report that the KDM3
      family of histone demethylases plays an important role in tumorigenic potential
      and survival of human colorectal CSCs by epigenetically activating Wnt target
      gene transcription. The depletion of KDM3 inhibits tumorigenic growth and
      chemoresistance of human colorectal CSCs. Mechanistically, KDM3 not only directly
      erases repressive H3K9me2 marks, but also helps to recruit histone
      methyltransferase MLL1 to promote H3K4 methylation, thereby promoting Wnt target
      gene transcription. Our results suggest that KDM3 is a critical epigenetic factor
      in Wnt signalling that orchestrates chromatin changes and transcription in human
      colorectal CSCs, identifying potential therapeutic targets for effective
      elimination of CSCs.

PMID- 28440297
TI  - Efficacy and safety of rectal nonsteroidal anti-inflammatory drugs for
      prophylaxis against post-ERCP pancreatitis: a systematic review and meta
      analysis.
AB  - Rectal nonsteroidal anti-inflammatory drugs (NSAIDs) are not commonly used
      clinically for preventing post-endoscopic retrograde cholangiopancreatography
      (ERCP) pancreatitis. To evaluate the efficacy and safety of NSAIDs for post-ERCP
      prophylaxis, we systematically reviewed sixteen randomized controlled trials
      (involving 6458 patients) that compared rectal NSAIDs with placebo or no
      treatment for post-ERCP pancreatitis prophylaxis updated to August 2016. GRADE
      framework was used to assess the quality of evidence. There was "high quality"
      evidence that rectal NSAIDs were associated with significant reduction in the
      risk of overall post-ERCP pancreatitis (RR, 0.55; 95% CI, 0.42-0.71). Subgroup
      analyses demonstrated that diclofenac (RR, 0.41; 95% CI, 0.19-0.90) was probably
      superior to indomethacin (RR, 0.58; 95% CI, 0.45-0.75), post-ERCP administration
      (RR, 0.46; 95% CI, 0.24-0.89) was probably superior to pre-ERCP (RR, 0.53; 95%
      CI, 0.42-0.67), and that mixed-risk population received more benefits (RR, 0.54;
      95% CI, 0.33-0.88) than average-risk population (RR, 0.60; 95% CI, 0.41-0.88),
      but less than high-risk population (RR, 0.41; 95% CI, 0.19-0.91). Moreover, "high
      quality" evidence showed that rectal NSAIDs were safe when given as a standard
      dose (RR = 0.80; 95% CI, 0.47-1.36). In conclusion, this meta-analysis revealed
      that rectal NSAIDs are effective and safe in the prevention of post-ERCP
      pancreatitis in populations with all levels of risk.

PMID- 28440298
TI  - Making medicines that save lives.

PMID- 28440296
TI  - Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of
      pancreatic cancer.
AB  - Pancreatic cancer is one of the deadliest human cancers, whose progression is
      highly dependent on the nervous microenvironment. The suppression of gene
      expression of nerve growth factor (NGF) may have great potential in pancreatic
      cancer treatment. Here we show that gold nanocluster-assisted delivery of siRNA
      of NGF (GNC-siRNA) allows efficient NGF gene silencing and pancreatic cancer
      treatment. The GNC-siRNA complex increases the stability of siRNA in serum,
      prolongs the circulation lifetime of siRNA in blood and enhances the cellular
      uptake and tumour accumulation of siRNA. The GNC-siRNA complex potently
      downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and
      effectively inhibits the tumour progression in three pancreatic tumour models
      (subcutaneous model, orthotopic model and patient-derived xenograft model)
      without adverse effects. Our study constitutes a straightforward but effective
      approach to inhibit pancreatic cancer via NGF knockdown, suggesting a promising
      therapeutic direction for pancreatic cancer.

PMID- 28440299
TI  - A reversible dendrite-free high-areal-capacity lithium metal electrode.
AB  - Reversible dendrite-free low-areal-capacity lithium metal electrodes have
      recently been revived, because of their pivotal role in developing beyond lithium
      ion batteries. However, there have been no reports of reversible dendrite-free
      high-areal-capacity lithium metal electrodes. Here we report on a strategy to
      realize unprecedented stable cycling of lithium electrodeposition/stripping with
      a highly desirable areal-capacity (12 mAh cm-2) and exceptional Coulombic
      efficiency (>99.98%) at high current densities (>5 mA cm-2) and ambient
      temperature using a diluted solvate ionic liquid. The essence of this strategy,
      that can drastically improve lithium electrodeposition kinetics by cyclic
      voltammetry premodulation, lies in the tailoring of the top solid-electrolyte
      interphase layer in a diluted solvate ionic liquid to facilitate a two
      dimensional growth mode. We anticipate that this discovery could pave the way for
      developing reversible dendrite-free metal anodes for sustainable battery
      chemistries.

PMID- 28440300
TI  - Insecticide-induced leg loss does not eliminate biting and reproduction in
      Anopheles gambiae mosquitoes.
AB  - Recent successes in malaria control have been largely attributable to the
      deployment of insecticide-based vector control tools such as bed nets and indoor
      residual spraying. Pyrethroid-treated bed nets are acutely neurotoxic to
      mosquitoes, inducing symptoms such as loss of coordination, paralysis, and
      violent spasms. One result of pyrethroid exposure often seen in laboratory tests
      is mosquito leg loss, a condition that has thus far been assumed to equate to
      mortality, as females are not expected to blood feed. However, whilst limb loss
      is unlikely to be adaptive, females with missing limbs may play a role in the
      propagation of both their species and pathogens. To test the hypothesis that leg
      loss inhibits mosquitoes from biting and reproducing, mosquitoes with one, two,
      or six legs were evaluated for their success in feeding upon a human. These
      experiments demonstrated that insecticide-induced leg loss had no significant
      effect upon blood feeding or egg laying success. We conclude that studies of
      pyrethroid efficacy should not discount mosquitoes that survive insecticide
      exposure with fewer than six legs, as they may still be capable of biting humans,
      reproducing, and contributing to malaria transmission.

PMID- 28440301
TI  - The environmental yeast Cryptococcus liquefaciens produces capsular and secreted
      polysaccharides with similar pathogenic properties to those of C. neoformans.
AB  - Invasive fungal infections, including cryptococcosis, are a growing threat to
      immunocompromised patients. Although Cryptococcus neoformans and Cryptococcus
      gattii are the main agents of human cryptococcosis, opportunistic infections by
      environmental species, such as C. liquefaciens, have been observed recently. The
      main Cryptococcus virulence factor is the production and secretion of
      polysaccharides (PS). Previously, we showed that both species produce PS of
      similar composition. Here, we examined the ultrastructure and biological activity
      of capsular and secreted PS from C. liquefaciens, and yeast pathogenicity to an
      invertebrate host, in comparison with C. neoformans. Ultrastructural analysis by
      high-resolution microscopy showed that both species produce large and complex
      capsules. PS from both species had indistinguishable effects on phagocytosis
      levels, NO production and the secretion of a variety of immune mediators.
      Challenge with C. liquefaciens or C. neoformans led to complete lethality of G.
      mellonella larvae. Treatment with C. liquefaciens PS could not protect mice
      against infection with C. neoformans. We conclude that polysaccharides of the
      environmental yeast C. liquefaciens have strikingly similar ultrastructural and
      biological properties to those of C. neoformans, highlighting the importance of
      monitoring the emergence of new fungal pathogens for which thermotolerance may be
      an important transitional step towards pathogenesis in humans.

PMID- 28440302
TI  - Performance of machine-learning scoring functions in structure-based virtual
      screening.
AB  - Classical scoring functions have reached a plateau in their performance in
      virtual screening and binding affinity prediction. Recently, machine-learning
      scoring functions trained on protein-ligand complexes have shown great promise in
      small tailored studies. They have also raised controversy, specifically
      concerning model overfitting and applicability to novel targets. Here we provide
      a new ready-to-use scoring function (RF-Score-VS) trained on 15 426 active and
      893 897 inactive molecules docked to a set of 102 targets. We use the full DUD-E
      data sets along with three docking tools, five classical and three machine
      learning scoring functions for model building and performance assessment. Our
      results show RF-Score-VS can substantially improve virtual screening performance:
      RF-Score-VS top 1% provides 55.6% hit rate, whereas that of Vina only 16.2% (for
      smaller percent the difference is even more encouraging: RF-Score-VS top 0.1%
      achieves 88.6% hit rate for 27.5% using Vina). In addition, RF-Score-VS provides
      much better prediction of measured binding affinity than Vina (Pearson
      correlation of 0.56 and -0.18, respectively). Lastly, we test RF-Score-VS on an
      independent test set from the DEKOIS benchmark and observed comparable results.
      We provide full data sets to facilitate further research in this area
      (http://github.com/oddt/rfscorevs) as well as ready-to-use RF-Score-VS
      (http://github.com/oddt/rfscorevs_binary).

PMID- 28440303
TI  - HCV Genotype 6 Increased the Risk for Hepatocellular Carcinoma Among Asian
      Patients With Liver Cirrhosis.
AB  - OBJECTIVES: Hepatitis C virus (HCV) infection is a well-documented risk factor
      for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and
      the genotypes show a great variety of geographic distribution. HCV genotype 6 is
      prevalent in Southeast Asia and has been less studied than the other genotypes.
      METHODS: This follow-up study was designed to evaluate the natural history of HCV
      genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV
      genotype 6 and 629 with other genotypes. The incidence of HCC per 1,000 person
      years of various HCV genotypes was estimated by dividing the new HCC cases to the
      person-years of follow-up. The adjusted hazards ratios (HRs) with 95% confidence
      intervals (CIs) were estimated by Cox's proportional hazards models. RESULTS:
      After 4072 person-years of follow-up, there were 96 newly-developed HCC cases,
      confirming an incidence of 23.6 per 1000 person-years. By stratifying cirrhosis
      at study entry, the cumulative risk of HCC among HCV genotype 6 vs. non-6 was 2.9
      vs. 2.2% for those without cirrhosis (P=0.45) and 76.2% (95% CI: 55.6-96.8%) vs.
      36.2% (95% CI: 28.7-39.1%) for those with cirrhosis (P<0.05), respectively. Among
      patients with cirrhosis, HCV genotype 6 was significantly associated with HCC
      compared to patients with non-6 genotypes, with the adjusted HR=2.12 (1.33-3.39),
      P<0.05. In a model treating patients with genotypes other than 1 or 6 as the
      reference, the adjusted HR for HCC for HCV genotypes 1 and 6 were 1.13 (0.56
      2.27) and 2.34 (1.12-4.86), respectively. CONCLUSIONS: Among patients with
      cirrhosis, those with HCV genotype 6 infection should be given high priority for
      antiviral therapy to decrease HCC risk and for vigilant adherence to HCC
      surveillance.

PMID- 28440304
TI  - The Natural History of Severe Acute Liver Injury.
AB  - OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and
      hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe
      acute hepatocyte necrosis without HE, has not been carefully defined nor studied.
      Our aim is to describe the clinical course of specifically defined ALI, including
      the risk and clinical predictors of poor outcomes, namely progression to ALF, the
      need for liver transplantation (LT) and death. METHODS: 386 subjects
      prospectively enrolled in the Acute Liver Failure Study Group registry between 1
      September 2008 through 25 October 2013, met criteria for ALI: International
      Normalized Ratio (INR)>=2.0 and alanine aminotransferase (ALT)>=10 * elevated
      (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol,
      APAP) ALI, or INR>=2.0, ALT>=10x elevated, and bilirubin>=3.0 mg/dl for non-APAP
      ALI, both groups without any discernible HE. Subjects who progressed to poor
      outcomes (ALF, death, LT) were compared, by univariate analysis, with those who
      recovered. A model to predict poor outcome was developed using the random forest
      (RF) procedure. RESULTS: Progression to a poor outcome occurred in 90/386 (23%),
      primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients
      comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of
      whom had a poor outcome). Of 82 variables entered into the RF procedure:
      etiology, bilirubin, INR, APAP level and duration of jaundice were the most
      predictive of progression to ALF, LT, or death. CONCLUSIONS: A majority of ALI
      cases are due to APAP, 93% of whom will improve rapidly and fully recover, while
      non-APAP patients have a far greater risk of poor outcome and should be targeted
      for early referral to a liver transplant center.

PMID- 28440305
TI  - Acute Kidney Injury in Cirrhosis: Baseline Serum Creatinine Predicts Patient
      Outcomes.
AB  - OBJECTIVES: The International Ascites Club (IAC) recently defined Stage 1 acute
      kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr)
      by >=0.3 mg/dl or by >=50% in <48 h from a stable value within 3 months. The
      baseline SCr may influence AKI risk and patient outcomes. The objective of this
      study is to determine in cirrhosis whether the baseline SCr has any effect on the
      in-hospital AKI course and patient survival. METHODS: North American Consortium
      for the Study of End-Stage Liver Disease is a consortium of tertiary-care
      hepatology centers prospectively enroling non-elective cirrhotic inpatients.
      Patients with different baseline SCr levels (<=0.5, 0.51-1.0, 1.01-1.5, >1.5
      mg/dl) were evaluated for the development of AKI, and compared for AKI outcomes
      and 30-day survival. RESULTS: 653 hospitalized cirrhotics (56.7+/-10years, 64%
      men, 30% with infection) were included. The incidence of AKI was 47% of enrolled
      patients. Patients with higher baseline SCr were more likely to develop AKI, with
      significantly higher delta and peak SCr (P<0.001) than the other groups, more
      likely to have a progressive AKI course (P<0.0001), associated with a
      significantly reduced 30-day survival (P<0.0001). Multivariate logistic
      regression showed that the delta SCr during an AKI episode to be the strongest
      factor impacting AKI outcomes and survival (P<0.001), with a delta SCr of 0.70
      mg/dl having a 68% sensitivity and 80% specificity for predicting 30-day
      mortality. CONCLUSIONS: Admitted cirrhotic patients with higher baseline SCr are
      at higher risk for in-hospital development of AKI, and more likely to have AKI
      progression with reduced survival. Therefore, such patients should be closely
      monitored and treated promptly for their AKI.

PMID- 28440306
TI  - An Evaluation of Factors Associated With Pathogenic PRSS1, SPINK1, CTFR, and/or
      CTRC Genetic Variants in Patients With Idiopathic Pancreatitis.
AB  - OBJECTIVES: We evaluated factors associated with pathogenic genetic variants in
      patients with idiopathic pancreatitis. METHODS: Genetic testing (PRSS1, CFTR,
      SPINK1, and CTRC) was performed in all eligible patients with idiopathic
      pancreatitis between 2010 to 2015. Patients were classified into the following
      groups based on a review of medical records: (1) acute recurrent idiopathic
      pancreatitis (ARIP) with or without underlying chronic pancreatitis; (2)
      idiopathic chronic pancreatitis (ICP) without a history of ARP; (3) an
      unexplained first episode of acute pancreatitis (AP)<35 years of age; and (4)
      family history of pancreatitis. Logistic regression analysis was used to
      determine the factors associated with pathogenic genetic variants. RESULTS: Among
      197 ARIP and/or ICP patients evaluated from 2010 to 2015, 134 underwent genetic
      testing. A total of 88 pathogenic genetic variants were found in 64 (47.8%)
      patients. Pathogenic genetic variants were identified in 58, 63, and 27% of
      patients with ARIP, an unexplained first episode of AP <35 years of age, and ICP
      without ARP, respectively. ARIP (OR: 18.12; 95% CI: 2.16-151.87; P=0.008) and an
      unexplained first episode of AP<35 years of age (OR: 2.46; 95% CI: 1.18-5.15;
      P=0.017), but not ICP, were independently associated with pathogenic genetic
      variants in the adjusted analysis. CONCLUSIONS: Pathogenic genetic variants are
      most likely to be identified in patients with ARIP and an unexplained first
      episode of AP<35 years of age. Genetic testing in these patient populations may
      delineate an etiology and prevent unnecessary diagnostic testing and procedures.

PMID- 28440307
TI  - LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPepsilon
      in granulocytes.
AB  - C/EBPepsilon is a critical transcriptional factor for granulocyte differentiation
      and function. Individuals with germline mutations of C/EBPepsilon fail to develop
      normal granulocytes and suffer from repeated infections. In order to gain a
      global view of the transcriptional machinery regulated by C/EBPepsilon, we
      performed whole-genome ChIP-Seq using mouse bone marrow cells. To complement the
      C/EBPepsilon DNA binding analyses, RNA-Sequencing was done in parallel using
      sorted mature and immature granulocytes from WT and C/EBPepsilon KO bone marrow.
      This approach led to the identification of several direct targets of
      C/EBPepsilon, which are potential effectors of its role in granulocytic
      differentiation and function. Interestingly, Trem1, a gene critical to
      granulocyte function, was identified as a direct C/EBPepsilon target gene. Trem1
      expression overlaps very closely with expression signature of C/EBPepsilon during
      hematopoietic development. Luciferase reporter and EMSA assays revealed that
      C/EBPepsilon binds to the regulatory elements of Trem1 and regulates its
      expression during granulocytic differentiation. In addition, we provide evidence
      that inflammatory stimuli (LPS) can also control the expression of Trem1
      independent of C/EBPepsilon. Overall, this study provides comprehensive profiling
      of the transcriptional network controlled by C/EBPepsilon during granulopoiesis
      and identifies Trem1 as one of its downstream effectors involved in eliciting an
      immune response.

PMID- 28440308
TI  - A Variation Code Accounts for the Perceived Roughness of Coarsely Textured
      Surfaces.
AB  - For decades, the dominant theory of roughness coding in the somatosensory nerves
      posited that perceived roughness was determined by the spatial pattern of
      activation in one population of tactile nerve fibers, namely slowly adapting type
      1 (SA1) afferents. Indeed, the perceived roughness of coarsely textured surfaces
      tracks the spatial variation in SA1 responses - the degree to which response
      strength varies across SA1 afferents. However, in a later study, the roughness of
      a different set of dot patterns was found to be a monotonic function of dot
      spacing, a result interpreted as evidence that roughness was determined by the
      strength of SA1 responses - the population firing rate - rather than their
      spatial layout. Then again, the spatial variation hypothesis was not tested
      directly as afferent responses to the conflicting patterns were not measured. To
      fill this gap, we simulated afferent responses to the dot patterns used in these
      roughness coding experiments using a model of skin mechanics. We then implemented
      the spatial variation and firing rate models of roughness based on these
      simulated responses to generate predictions of perceived roughness. We found that
      the spatial variation model accounts for perceived roughness under all tested
      conditions whereas the firing rate model does not.

PMID- 28440309
TI  - Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal
      neurogenesis.
AB  - Adult hippocampal neurogenesis is a remarkable form of brain plasticity through
      which new neurons are generated throughout life. Despite its important roles in
      cognition and emotion and its modulation in various preclinical disease models,
      the functional importance of adult hippocampal neurogenesis in human health has
      not been revealed because of a lack of tools for monitoring adult neurogenesis in
      vivo. Therefore, we performed an unbiased proteomics screen to identify novel
      proteins expressed during neuronal differentiation using a human neural stem cell
      model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative
      secreted marker of immature neurons. Exogenous Gpc2 binds to FGF2 and inhibits
      FGF2-induced neural progenitor cell proliferation. Gpc2 is enriched in neurogenic
      regions of the adult brain. Its expression is increased by physiological stimuli
      that increase hippocampal neurogenesis and decreased in transgenic models in
      which neurogenesis is selectively ablated. Changes in neurogenesis also result in
      changes in Gpc2 protein level in cerebrospinal fluid (CSF). Gpc2 is detectable in
      adult human CSF, and first pilot experiments with a longitudinal cohort indicate
      a decrease over time. Thus, Gpc2 may serve as a potential marker to monitor adult
      neurogenesis in both animal and human physiology and disease, warranting future
      studies.

PMID- 28440310
TI  - Klf5 Mediates Odontoblastic Differentiation through Regulating Dentin-Specific
      Extracellular Matrix Gene Expression during Mouse Tooth Development.
AB  - Klf5, a member of the Kruppel-like transcription factor family, has essential
      roles during embryonic development, cell proliferation, differentiation,
      migration and apoptosis. This study was to define molecular mechanism of Klf5
      during the odontoblastic differentiation. The expression of Klf5, odontoblast
      differentiation markers, Dspp and Dmp1 was co-localized in odontoblastic cells at
      different stages of mouse tooth development and mouse dental papilla mesenchymal
      cells. Klf5 was able to promote odontoblastic differentiation and enhance mineral
      formation of mouse dental papilla mesenchymal cells. Furthermore, overexpression
      of Klf5 could up-regulate Dspp and Dmp1 gene expressions in mouse dental papilla
      mesenchymal cells. In silico analysis identified that several putative Klf5
      binding sites in the promoter and first intron of Dmp1 and Dspp genes that are
      homologous across species lines. Electrophoretic mobility shift assay and
      chromatin immunoprecipitation analysis indicated that Klf5 bound to these motifs
      in vitro and in intact cells. The responsible regions of Dmp1 gene were located
      in the promoter region while effect of Klf5 on Dspp activity was in the first
      intron of Dspp gene. Our results identify Klf5 as an activator of Dmp1 and Dspp
      gene transcriptions by different mechanisms and demonstrate that Klf5 plays a
      pivotal role in odontoblast differentiation.

PMID- 28440311
TI  - Efficacy and safety of rectal 5-aminosalicylic acid versus corticosteroids in
      active distal ulcerative colitis: a systematic review and network meta-analysis.
AB  - Topical 5-aminosalicylic acid (5-ASA) and corticosteroids are used frequently in
      the treatment of active distal ulcerative colitis (UC). Our study aimed to
      determine the efficacy and safety of different topical drugs used to treat active
      distal UC. A random-effects model within a Bayesian framework was utilized to
      compare treatment effects and safety as odds ratios (ORs) with corresponding 95%
      credible intervals (CrI). The surface under the cumulative ranking area (SUCRA)
      and median rank (MR) with corresponding 95% CrI were calculated to rank the
      treatment outcomes. In the induction of clinical and endoscopic remission, most
      regimens showed significant advantages over placebo except topical budesonide 0.5
      mg/d and hydrocortisone 100 mg/d. According to SUCRA and MR values, rectal 5-ASA
      1.5 to 2.0 g/d + Beclomethasone dipropionate (BDP) 3 mg/d rendered the highest
      probability of being the best regimen to achieve clinical and endoscopic
      remission, followed by the separate use of 5-ASA 4 g/d and BDP 3 mg/d. The
      occurrence of adverse events was not significantly different between each
      treatments and placebo. In conclusion, the combined use of topical 5-ASA and BDP
      proved to be the best choice for active distal UC and further well-designed
      researches are warranted to assess its efficacy and safety.

PMID- 28440312
TI  - Expanding role for type I Interferons in restricting HIV growth.

PMID- 28440313
TI  - Regulation is no bad thing.

PMID- 28440314
TI  - The peripheral blood proteome signature of idiopathic pulmonary fibrosis is
      distinct from normal and is associated with novel immunological processes.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial
      pneumonia. The disease pathophysiology is poorly understood and the etiology
      remains unclear. Recent advances have generated new therapies and improved
      knowledge of the natural history of IPF. These gains have been brokered by
      advances in technology and improved insight into the role of various genes in
      mediating disease, but gene expression and protein levels do not always
      correlate. Thus, in this paper we apply a novel large scale high throughput
      aptamer approach to identify more than 1100 proteins in the peripheral blood of
      well-characterized IPF patients and normal volunteers. We use systems biology
      approaches to identify a unique IPF proteome signature and give insight into
      biological processes driving IPF. We found IPF plasma to be altered and enriched
      for proteins involved in defense response, wound healing and protein
      phosphorylation when compared to normal human plasma. Analysis also revealed a
      minimal protein signature that differentiated IPF patients from normal controls,
      which may allow for accurate diagnosis of IPF based on easily-accessible
      peripheral blood. This report introduces large scale unbiased protein discovery
      analysis to IPF and describes distinct biological processes that further inform
      disease biology.

PMID- 28440316
TI  - Modest and Severe Maternal Iron Deficiency in Pregnancy are Associated with Fetal
      Anaemia and Organ-Specific Hypoxia in Rats.
AB  - Prenatal iron-deficiency (ID) is known to alter fetal developmental trajectories,
      which predisposes the offspring to chronic disease in later life, although the
      underlying mechanisms remain unclear. Here, we sought to determine whether
      varying degrees of maternal anaemia could induce organ-specific patterns of
      hypoxia in the fetuses. Pregnant female Sprague Dawley rats were fed iron
      restricted or iron-replete diets to induce a state of moderate (M-ID) or severe
      ID (S-ID) alongside respective controls. Ultrasound biomicroscopy was performed
      on gestational day (GD)20 to assess uterine and umbilical artery blood flow
      patterns. On GD21, tissues were collected and assessed for hypoxia using
      pimonidazole staining. Compared to controls, maternal haemoglobin (Hb) in M- and
      S-ID were reduced 17% (P < 0.01) and 48% (P < 0.001), corresponding to 39% (P <
      0.001) and 65% (P < 0.001) decreases in fetal Hb. Prenatal ID caused asymmetric
      fetal growth restriction, which was most pronounced in S-ID. In both severities
      of ID, umbilical artery resistive index was increased (P < 0.01), while
      pulsatility index only increased in S-ID (P < 0.05). In both M-and S-ID, fetal
      kidneys and livers showed evidence of hypoxia (P < 0.01 vs. controls), whereas
      fetal brains and placentae remained normoxic. These findings indicate prenatal ID
      causes organ-specific fetal hypoxia, even in the absence of severe maternal
      anaemia.

PMID- 28440315
TI  - Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells.
AB  - TET2 is a dioxygenase that catalyses multiple steps of 5-methylcytosine
      oxidation. Although TET2 mutations frequently occur in various types of
      haematological malignancies, the mechanism by which they increase risk for these
      cancers remains poorly understood. Here we show that Tet2-/- mice develop
      spontaneous myeloid, T- and B-cell malignancies after long latencies. Exome
      sequencing of Tet2-/- tumours reveals accumulation of numerous mutations,
      including Apc, Nf1, Flt3, Cbl, Notch1 and Mll2, which are recurrently
      deleted/mutated in human haematological malignancies. Single-cell-targeted
      sequencing of wild-type and premalignant Tet2-/- Lin-c-Kit+ cells shows higher
      mutation frequencies in Tet2-/- cells. We further show that the increased
      mutational burden is particularly high at genomic sites that gained 5
      hydroxymethylcytosine, where TET2 normally binds. Furthermore, TET2-mutated
      myeloid malignancy patients have significantly more mutational events than
      patients with wild-type TET2. Thus, Tet2 loss leads to hypermutagenicity in
      haematopoietic stem/progenitor cells, suggesting a novel TET2 loss-mediated
      mechanism of haematological malignancy pathogenesis.

PMID- 28440317
TI  - Live cell imaging of mitochondria following targeted irradiation in situ reveals
      rapid and highly localized loss of membrane potential.
AB  - The reliance of all cell types on the mitochondrial function for survival makes
      mitochondria an interesting target when trying to understand their role in the
      cellular response to ionizing radiation. By harnessing highly focused carbon ions
      and protons using microbeams, we have performed in situ live cell imaging of the
      targeted irradiation of individual mitochondria stained with Tetramethyl
      rhodamine ethyl ester (TMRE), a cationic fluorophore which accumulates
      electrophoretically in polarized mitochondria. Targeted irradiation with both
      carbon ions and protons down to beam spots of <1 MUm induced a near instant loss
      of mitochondrial TMRE fluorescence signal in the targeted area. The loss of TMRE
      after targeted irradiation represents a radiation induced change in mitochondrial
      membrane potential. This is the first time such mitochondrial responses have been
      documented in situ after targeted microbeam irradiation. The methods developed
      and the results obtained have the ability to shed new light on not just
      mitochondria's response to radiation but to further elucidate a putative
      mechanism of radiation induced depolarization and mitochondrial response.

PMID- 28440318
TI  - Corrigendum: Proteogenomic integration reveals therapeutic targets in breast
      cancer xenografts.

PMID- 28440319
TI  - Synthesis of extended polycyclic aromatic hydrocarbons by oxidative tandem
      spirocyclization and 1,2-aryl migration.
AB  - The extended polycyclic aromatic hydrocarbons (PAHs) have received significant
      interdisciplinary attention due to their semiconducting applications in diverse
      organic electronics as well as intriguing structural interests of well-defined
      graphene segments. Herein, a highly efficient oxidative spirocyclization and 1,2
      aryl migration tandem synthetic method for the construction of extended
      polyaromatic hydrocarbons (PAHs) has been developed. The CuCl-catalyst/PhCO3tBu
      or DDQ oxidation system in the presence of trifluoroacetic acid enables the
      selective single-electron oxidation to take place preferentially at the more
      electron-rich alkene moiety of o-biphenylyl-substituted methylenefluorenes,
      giving rise to the subsequent tandem process. A variety of structurally diverse
      extended PAHs including functionalized dibenzo[g,p]chrysenes, benzo[f]naphtho[1,2
      s]picene, hexabenzo[a,c,fg,j,l,op]tetracene, tetrabenzo[a,c,f,m]phenanthro[9,10
      k]tetraphene, tetrabenzo[a,c,f,k]phenanthro[9,10-m]tetraphene,
      tetrabenzo[a,c,f,o]phenanthro[9,10-m]picene and S-type helicene have been readily
      synthesized.

PMID- 28440321
TI  - Association of comorbid disease burden at diagnosis with higher tumor grade in
      men with non-metastatic prostate cancer.
AB  - BACKGROUND: While older age is associated with higher tumor grade, it is unknown
      whether comorbid disease burden has a similar, independent association. We sought
      to evaluate the impact of comorbid disease burden on tumor grade at diagnosis as
      indicated by biopsy Gleason score. METHODS: We conducted an observational cohort
      study of 1260 men newly diagnosed with non-metastatic prostate cancer from 1998
      to 2004 at two Veterans Affairs Medical Centers. Multivariable ordinal and
      multinomial logistic regression were used to evaluate the association between
      Charlson Comorbidity Index score and biopsy Gleason score. RESULTS: Men with
      Charlson scores of 2 (odds ratio (OR) 1.8, P<0.001) and 3+ (OR 1.8, P<0.001) had
      significantly greater odds of higher Gleason scores, compared with men with
      Charlson scores of 0. In a multinomial logistic regression model predicting
      Gleason 7 vs ?6, only men with Charlson scores of 2 (OR 1.6, P=0.01) had greater
      odds of having a Gleason 7 tumor, compared with those with Charlson scores of 0.
      In a multinomial logistic regression model predicting Gleason 8-10 vs ?6, those
      with Charlson scores of 1 (OR 1.6, P=0.047), 2 (OR 2.8, P=0.01) and 3+ (OR 2.9,
      P=0.001) had higher odds of having a Gleason 8-10 tumor. CONCLUSIONS: Moderate-to
      heavy comorbid disease burden at diagnosis may be associated with high tumor
      grade, independent of age, and is a stronger predictor of Gleason 8-10 than
      Gleason 7 disease.

PMID- 28440320
TI  - A review of pomegranate in prostate cancer.
AB  - BACKGROUND: Preclinical studies showing that pomegranate juice and its components
      inhibit prostate cancer led to multiple clinical trials to determine whether
      pomegranate products could slow the growth of prostate cancer. This review
      summarizes the preclinical data and discusses the results of the clinical trials.
      METHODS: Trials targeted patients on active surveillance, neoadjuvant patients,
      patients with biochemical recurrence (BCR) following local therapy for prostate
      cancer, and patients with metastatic castration-resistant prostate cancer
      (mCRPC). RESULTS: In the BCR patient population, early phase II trials of both
      pomegranate juice and extract showed significant lengthening of PSA doubling time
      (PSADT), and confirmed the safety of pomegranate products. While a placebo
      controlled phase III trial determined that pomegranate extract did not
      significantly prolong PSADT in BCR patients, a preplanned subset analysis of
      patients with the manganese superoxide dismutase (MnSOD) AA genotype showed
      greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant
      population, a large trial demonstrated a significant increase in urolithin A and
      a non-significant reduction in 8-hydroxy-2-deoxyguanosine, a marker of oxidation
      in prostate cancer tissue, on the pomegranate arm vs the placebo arm. In
      addition, a randomized clinical trial of a polyphenol-rich multicomponent food
      supplement that included a 31.25% pomegranate extract found significant slowing
      of PSA increase in the food supplement arm vs placebo in men on active
      surveillance and those experiencing BCR. CONCLUSIONS: Pomegranate juice and
      extract are safe but did not significantly improve outcomes in BCR patients in a
      large placebo-controlled trial. However a subset of BCR patients with the MnSOD
      AA genotype appear to respond positively to the antioxidant effects of
      pomegranate treatment. Phase II trials of 100% pomegranate products in
      neoadjuvant patients and patients with mCRPC were negative. A multicomponent food
      supplement showed promising results in a phase II study in active surveillance
      and BCR patients.

PMID- 28440322
TI  - Does mpMRI improve clinical criteria in selecting men with prostate cancer for
      active surveillance?
AB  - BACKGROUND: Active surveillance (AS) has excellent short to medium term outcomes
      in well-selected prostate cancer patients. Traditional biopsy-based selection
      criteria have been criticized for inaccurate determination of cancer grade and
      extent. We evaluated the incremental benefit of multiparametric magnetic
      resonance imaging (mpMRI) in patient selection using various AS criteria.
      METHODS: We retrospectively evaluated men who received mpMRI before radical
      prostatectomy between 2011 and 2014. Patients were classified as suitable for AS
      using four criteria: (1) Epstein, (2) National Comprehensive Cancer Network
      (NCCN) low-risk or (3) extended criteria (Gleason ?3+4, PSA ?15 ng/ml, clinical
      stage ?T2b) using clinical parameters. The incremental value of mpMRI was
      evaluated against the referent standard of surgical pathology in determining
      suitability for AS using sensitivity, specificity, likelihood ratios (LRs) and
      area under receiver operating curves (AUCs). RESULTS: We evaluated 208 men. Only
      one man fulfilled Epstein criteria (1) at pathology, who was neither identified
      using clinical criteria nor mpMRI. Using (2), clinical criteria had a sensitivity
      of 80%, specificity 75%, LR+ 3.3, LR- 0.3, AUC 0.78, while combined clinical
      mpMRI criteria achieved a sensitivity of 80%, specificity 99.5% (P<0.01), LR+
      162, LR- 0.2 and AUC 0.90 (P<0.01 compared to clinical). Using (3), clinical
      criteria had a sensitivity of 74%, specificity 47%, LR+ 1.4, LR- 0.6, AUC 0.60,
      while combined clinical-mpMRI criteria achieved a sensitivity of 26% (P<0.01),
      specificity 97% (P<0.01), LR+ 8.3, LR- 0.8 and AUC 0.62 (P=0.85). CONCLUSIONS:
      Addition of mpMRI significantly improved selection of men for AS using NCCN low
      risk criteria. For selecting men with limited prognostic grade group 2, mpMRI
      significantly improved specificity at the expense of sensitivity.

PMID- 28440324
TI  - Lutetium-177-labelled anti-prostate-specific membrane antigen antibody and
      ligands for the treatment of metastatic castrate-resistant prostate cancer: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Promising therapeutic results of the prostate-specific membrane
      antigen (PSMA) ligand have been shown when labelling with lutetium-177 (177Lu).
      We performed a systematic review and meta-analysis to assess the therapeutic
      response of 177Lu-PSMA in the treatment of metastatic castration-resistant
      prostate cancer (mCRPC). METHODS: A systematic review was conducted using
      electronic databases up to December 2016. Two reviewers independently extracted
      data and assessed methodological quality. The main outcome of interest was
      antitumour biochemical response of 177Lu-PSMA, analysing two measures: 'any PSA
      decline' and '>50% decline' from baseline. A random-effects meta-analysis was
      used to calculate the pooled proportion across studies. The I2 statistic was
      calculated in each case to investigate the extent of heterogeneity across the
      studies. A sensitivity analysis was conducted removing two studies, which were
      presented as abstracts and proportions were summarised by chemical type (177Lu
      J591/DKZ/I&T). All analyses were conducted using Stata v14. RESULTS: A total of
      10 studies were included in the analysis giving a total sample size of 369, 220
      (of 334 analysable) experienced any PSA decline. The pooled proportion of
      patients with any PSA decline was 68% (95% confidence interval (CI): 61-74). The
      I2 statistic was 39.1% (P=0.11) suggesting minor heterogeneity between results.
      The pooled proportion of patients with >50% PSA decline was 37% (95% CI: 22-52).
      The I2 statistic was 91.0% (P<0.001) suggesting substantial heterogeneity between
      results. On subgroup analysis, a higher proportion of patients in the 177Lu
      DKZ/I&T subgroup had a PSA decline >50%, however, it can be seen that the 177Lu
      DKZ/I&T subgroup had a substantial amount of heterogeneity across studies.
      CONCLUSIONS: This review suggests promising early results for the treatment of
      mCRPC, especially from patients treated with the more recently developed
      radioligands. Overall, our meta-analysis showed that approximately two-thirds of
      patients had a biochemical response. Randomised-controlled trials would be
      necessary to verify its effectiveness against current systemic therapies and
      create an ideal treatment protocol.

PMID- 28440325
TI  - Multiparametric MRI/ultrasound fusion-guided biopsy decreases detection of
      indolent cancer in African-American men.
AB  - BACKGROUND: Analysis of systematic 12-core biopsies (SBx) has shown that African
      American (AA) men tend to harbor higher risk prostate cancer (PCa) at
      presentation relative to other races. Multiparametric magnetic resonance imaging
      (mpMRI) and MRI-ultrasound fusion-guided biopsy (FBx) have been shown to diagnose
      more intermediate- and high-risk PCa in the general population; however, the
      efficacy in AA remains largely uncharacterized. We aim to evaluate the utility of
      FBx in an AA patient cohort. METHODS: Men suspected of PCa underwent an mpMRI and
      FBx with concurrent SBx from 2007 to 2015 in this institutional review board
      approved prospective cohort study. Patient demographics, imaging and fusion
      biopsy variables were collected. chi2, Mann-Whitney U-test and McNemar's tests
      were performed to compare proportions, means and paired variables, respectively.
      Clinically significant PCa (CSPCa) was defined as Gleason score ?3+4. RESULTS:
      Fusion biopsy demonstrated exact agreement with SBx risk categories in 64% of AA
      men. There was no statistically significant difference in the detection of CSPCa
      between FBx vs SBx (68 vs 62 cases, P=0.36). However, FBx detected 41% fewer
      cases of clinically insignificant PCa (CIPCa) compared with SBx (FBx 30 vs SBx 51
      cases, P=0.0004). The combined FBx/SBx biopsy approach detected significantly
      more cases of CSPCa (FBx/SBx 80 vs SBx 62 cases, P=0.004) while detecting
      comparable number of cases of CIPCa (FBx/SBx 45 vs SBx 51 cases, P=0.37) compared
      with SBx alone. FBx/SBx also detected more CSPCa in patients with a history of
      prior negative SBx (FBx/SBx 28 vs 19 cases, P=0.003). CONCLUSIONS: FBx when used
      in combination with SBx detected more cases of CSPCa while not significantly
      increasing the diagnosis of CIPCa in AA men. Future multicenter studies will be
      needed to validate ultimately the clinical implications of FBx in AA patients.

PMID- 28440323
TI  - Increased dietary and circulating lycopene are associated with reduced prostate
      cancer risk: a systematic review and meta-analysis.
AB  - BACKGROUND: Prostate cancer (PCa) is the fifth leading cause of cancer-related
      deaths worldwide. Many epidemiological studies have investigated the association
      between prostate cancer and lycopene, however, results have been inconsistent.
      This study aims to determine the impact of dietary and circulating concentrations
      of lycopene on PCa risk and to investigate potential dose-response associations.
      METHODS: We conducted a systematic review and dose-response meta-analysis for the
      for the association between dietary and circulating lycopene and PCa risk.
      Eligible studies were published before 1 December 2016 and were identified from
      PubMed, Web of Science and the Cochrane Library. We estimated pooled relative
      risk ratios (RR) and 95% confidence intervals (CI) using random and fixed effects
      models. Linear and nonlinear dose-response relationships were also evaluated for
      PCa risk. RESULTS: Forty-two studies were included in the analysis, which
      included 43 851 cases of PCa reported from 692 012 participants. Both dietary
      intake (RR=0.88, 95% CI: 0.78-0.98, P=0.017) and circulating concentrations
      (RR=0.88, 95% CI: 0.79-0.98, P=0.019) of lycopene were significantly associated
      with reduced PCa risk. Sensitivity analyses within the dose-response analysis
      further revealed a significant linear dose-response for dietary lycopene and PCa
      risk such that PCa decreased by 1% for every additional 2 mg of lycopene consumed
      (P=0.026). Additionally, PCa risk decreased by 3.5 to 3.6% for each additional 10
      MUgdl-1 of circulating lycopene in the linear and nonlinear models respectively
      (plinear=0.004, pnonlinear=0.006). While there were no associations between
      lycopene and advanced PCa, there was a trend for protection against PCa
      aggressiveness (RR=0.74, 95% CI: 0.55-1.00, P=0.052). CONCLUSIONS: Our data
      demonstrate that higher dietary and circulating lycopene concentrations are
      inversely associated with PCa risk. This was accompanied by dose-response
      relationships for dietary and circulating lycopene. However, lycopene was not
      associated with a reduced risk of advanced PCa. Further studies are required to
      determine the mechanisms underlying these associations.

PMID- 28440326
TI  - Complex multifractal nature in Mycobacterium tuberculosis genome.
AB  - The mutifractal and long range correlation (C(r)) properties of strings, such as
      nucleotide sequence can be a useful parameter for identification of underlying
      patterns and variations. In this study C(r) and multifractal singularity function
      f(alpha) have been used to study variations in the genomes of a pathogenic
      bacteria Mycobacterium tuberculosis. Genomic sequences of M. tuberculosis
      isolates displayed significant variations in C(r) and f(alpha) reflecting
      inherent differences in sequences among isolates. M. tuberculosis isolates can be
      categorised into different subgroups based on sensitivity to drugs, these are DS
      (drug sensitive isolates), MDR (multi-drug resistant isolates) and XDR (extremely
      drug resistant isolates). C(r) follows significantly different scaling rules in
      different subgroups of isolates, but all the isolates follow one parameter
      scaling law. The richness in complexity of each subgroup can be quantified by the
      measures of multifractal parameters displaying a pattern in which XDR isolates
      have highest value and lowest for drug sensitive isolates. Therefore C(r) and
      multifractal functions can be useful parameters for analysis of genomic
      sequences.

PMID- 28440327
TI  - Bladder cancer: Targeting oncofetal glycosaminoglycans.

PMID- 28440328
TI  - Prostate cancer: Antagonizing AR: MYC affects transcription.

PMID- 28440330
TI  - In the news: From AACR 2017.

PMID- 28440331
TI  - Immunotherapy: Does adjuvant ipilimumab have little adverse effect on quality of
      life?

PMID- 28440329
TI  - Role of the virulence plasmid in acid resistance of Shigella flexneri.
AB  - Virulence plasmid (VP) acquisition was a key step in the evolution of Shigella
      from a non-pathogenic Escherichia coli ancestor to a pathogenic genus. In
      addition, the co-evolution and co-ordination of chromosomes and VPs was also a
      very important step in the evolutionary process. To investigate the cross-talk
      between VPs and bacterial chromosomes, we analyzed the expression profiles of
      protein complexes and protein monomers in three wild-type Shigella flexneri
      strains and their corresponding VP deletion mutants. A non-pathogenic wild-type
      E. coli strain and mutant E. coli strains harboring three Shigella VPs were also
      analyzed. Comparisons showed that the expression of chromosome-encoded proteins
      GadA/B and AtpA/D, which are associated with intracellular proton flow and pH
      tuning of bacterial cells, was significantly altered following acquisition or
      deletion of the VP. The acid tolerance of the above strains was also compared,
      and the results confirmed that the presence of the VP reduced the bacterial
      survival rate in extremely acidic environments, such as that in the host stomach.
      These results further our understanding of the evolution from non-pathogenic E.
      coli to Shigella, and highlight the importance of co-ordination between
      heterologous genes and the host chromosome in the evolution of bacterial species.

PMID- 28440332
TI  - Immunotherapy: Reinvigorated T-cell numbers counterbalance tumour burden.

PMID- 28440333
TI  - Immunotherapy: Cul-TIL-vating uveal melanoma regression.

PMID- 28440334
TI  - Trends in perinatal mortality and its risk factors in Japan: Analysis of vital
      registration data, 1979-2010.
AB  - As Japan has achieved one of the lowest perinatal mortality rates (PMR), our
      study aims to estimate trends in and risk factors for perinatal mortality among
      singleton births in Japan. We used Japanese vital registration data to assess
      trends in and risk factors for perinatal outcomes between 1979 and 2010. Birth
      and death registration data were merged. An autoregressive integrated moving
      average model was fitted separately by sex to the PMR and the proportion of
      stillbirths. A multilevel Poisson regression model was used to estimate risk
      factors for perinatal mortality. Between 1979 and 2010 there were 40,833,957
      pregnancies and 355,193 perinatal deaths, the PMR decreased from 18.86 per 1,000
      all births to 3.25 per 1,000 all births, and the proportion of stillbirths
      increased from 83.6% to 92.1%. Key risk factors for perinatal mortality were low
      or high birth weight, prematurity and post maturity, and being from poorer or
      unemployed families. A higher proportion of excess perinatal deaths could be
      averted by effective policies to prevent stillbirths and improved research into
      their interventions and risk factors. As the cost and challenge of maintaining
      perinatal mortality gains increases, policies need to be targeted towards higher
      risk groups and social determinants of health.

PMID- 28440336
TI  - Ultrahigh energy density harvested from domain-engineered relaxor ferroelectric
      single crystals under high strain rate loading.
AB  - Relaxor ferroelectric single crystals have triggered revolution in
      electromechanical systems due to their superior piezoelectric properties. Here
      the results are reported on experimental studies of energy harvested from (1-y
      x)Pb(In1/2Nb1/2)O3-(y)Pb(Mg1/3Nb2/3)O3-(x)PbTiO3 (PIN-PMN-PT) crystals under high
      strain rate loading. Precise control of ferroelectric properties through
      composition, size and crystallographic orientation of domains made it possible to
      identify single crystals that release up to three times more electric charge
      density than that produced by PbZr0.52Ti0.48O3 (PZT 52/48) and PbZr0.95Ti0.05O3
      (PZT 95/5) ferroelectric ceramics under identical loading conditions. The
      obtained results indicate that PIN-PMN-PT crystals became completely depolarized
      under 3.9 GPa compression. It was found that the energy density generated in the
      crystals during depolarization in the high voltage mode is four times higher than
      that for PZT 52/48 and 95/5. The obtained results promise new single crystal
      applications in ultrahigh-power transducers that are capable of producing
      hundreds kilovolt pulses and gigawatt-peak power microwave radiation.

PMID- 28440335
TI  - Mycobacterium tuberculosis PE_PGRS41 Enhances the Intracellular Survival of M.
      smegmatis within Macrophages Via Blocking Innate Immunity and Inhibition of Host
      Defense.
AB  - The success of Mycobacterium tuberculosis (M. tuberculosis) as a pathogen is
      largely contributes to its ability to manipulate the host immune responses. The
      genome of M. tuberculosis encodes multiple immune-modulatory proteins, including
      several members of the multi-genic PE_PPE family. Despite of intense research,
      the roles of PE_PGRS proteins in mycobacterial pathogenesis remain elusive. The
      function of M. tuberculosis PE_PGRS41, characterized by an extended and unique C
      terminal domain, was studied. Expression of PE_PGRS41 in Mycobacterium smegmatis,
      a non-pathogenic species intrinsically deficient of PE_PGRS, severely impaired
      the resistance of the recombinant to multiple stresses via altering the cell wall
      integrity. Macrophages infected by M. smegmatis harboring PE_PGRS41 decreased the
      production of TNF-alpha, IL-1beta and IL-6. In addition, PE_PGRS41 boosted the
      survival of M. smegmatis within macrophage accompanied with enhanced cytotoxic
      cell death through inhibiting the cell apoptosis and autophagy. Taken together,
      these results implicate that PE_PGRS41 is a virulence factor of M. tuberculosis
      and sufficient to confer pathogenic properties to M. smegmatis.

PMID- 28440337
TI  - Corrigendum: Patient-specific hepatocyte-like cells derived from induced
      pluripotent stem cells model pazopanib-mediated hepatotoxicity.

PMID- 28440338
TI  - Unravelling the contributions of motor experience and conceptual knowledge in
      action perception: A training study.
AB  - Prior knowledge affects how we perceive the world and the sensorimotor system
      actively guides our perception. An ongoing dispute regards the extent to which
      prior motor knowledge versus conceptual knowledge modulates the observation of
      others' actions. Research indicates that motor experience increases motor
      activation during action perception. Other research, however, has shown that
      conceptual familiarity with actions also modulates motor activation, i.e.,
      increased motor activation during observation of unfamiliar, compared to
      conceptually familiar, actions. To begin to disentangle motor from conceptual
      contributions to action perception, we uniquely combined motoric and conceptual
      interventions into one design. We experimentally manipulated participants'
      experience with both motoric skills and conceptual knowledge, via motor training
      of kinematically challenging actions and contextual information about the action,
      respectively, in a week-long training session. Measurements of the effects on
      motor activity measured via electroencephalography (EEG) during pre- and post
      training action observation were compared. We found distinct, non-interacting
      effects of both manipulations: Motor training increased motor activation, whereas
      additional conceptual knowledge decreased motor activation. The findings indicate
      that both factors influence action perception in a distinct and parallel manner.
      This research speaks to previously irreconcilable findings and provides novel
      insights about the distinct roles of motor and conceptual contributions to action
      perception.

PMID- 28440339
TI  - Polyamorphism in Yb-based metallic glass induced by pressure.
AB  - The Yb62.5Zn15Mg17.5Cu5 metallic glass is investigated using synchrotron x-ray
      total scattering method up to 38.4 GPa. The polyamorphic transformation from low
      density to high density with a transition region between 14.1 and 25.2 GPa is
      observed, accompanying with a volume collapse reflected by a discontinuousness of
      isothermal bulk modulus. This collapse is caused by that distortional icosahedron
      short range order precedes to perfect icosahedron, which might link to Yb 4f
      electron delocalization upon compression, and match the result of in situ
      electrical resistance measurement under high pressure conditions. This discovery
      in Yb-based metallic glass, combined with the previous reports on other metallic
      glass systems, demonstrates that pressure induced polyamorphism is the general
      behavior for typical lanthanide based metallic glasses.

PMID- 28440340
TI  - Comparative genomics and metabolomics analyses of the adaptation mechanism in
      Ketogulonicigenium vulgare-Bacillus thuringiensis consortium.
AB  - Adaptive evolution by serial subcultivation of co-cultured Bacillus thuringiensis
      and Ketogulonicigenium vulgare significantly enhanced the productivity of 2-keto
      L-gulonic acid in two-step vitamin C production. The adaptation mechanism in K.
      vulgare-B. thuringiensis consortium was investigated in this study based on
      comparative genomics and metabolomics studies. It was found that the growth, anti
      oxidation, transcription and regulation were significantly enhanced in the
      adapted consortium. The mutation of the genes, which encode amidohydrolase in
      adapted K. vulgare (K150) and amino acid permease in adapted B. thuringiensis
      (B150), resulted in the increase of some amino acids levels in each species, and
      further enhanced the metabolic exchange and growth ability of the two species.
      Besides, the mutation of the gene encoding spore germination protein enhanced the
      metabolic levels of tricarboxylic acid cycle, and decreased the sporulation in
      B150, which induced its growth. The mutation of the genes, which encode NADPH
      nitroreductase in K150 and NADPH-dependent FMN reductase in B150, may enhance the
      ability of anti-oxidation. Overall, the long-term adaptation of K. vulgare and B.
      thuringiensis influenced the global regulation and made them more inseparable in
      metabolite exchange. Our work will provide ideas for the molecular design and
      optimization in microbial consortium.

PMID- 28440341
TI  - Quantitative profiling of the UGT transcriptome in human drug-metabolizing
      tissues.
AB  - Alternative splicing as a mean to control gene expression and diversify function
      is suspected to considerably influence drug response and clearance. We report the
      quantitative expression profiles of the human UGT genes including alternatively
      spliced variants not previously annotated established by deep RNA-sequencing in
      tissues of pharmacological importance. We reveal a comprehensive quantification
      of the alternative UGT transcriptome that differ across tissues and among
      individuals. Alternative transcripts that comprise novel in-frame sequences
      associated or not with truncations of the 5'- and/or 3'- termini, significantly
      contribute to the total expression levels of each UGT1 and UGT2 gene averaging
      21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1.
      Quantitative data expose preferential tissue expression patterns and remodeling
      in favor of alternative variants upon tumorigenesis. These complex alternative
      splicing programs have the strong potential to contribute to interindividual
      variability in drug metabolism in addition to diversify the UGT proteome.

PMID- 28440342
TI  - Significant variation between SNP-based HLA imputations in diverse populations:
      the last mile is the hardest.
AB  - Four single nucleotide polymorphism (SNP)-based human leukocyte antigen (HLA)
      imputation methods (e-HLA, HIBAG, HLA*IMP:02 and MAGPrediction) were trained
      using 1000 Genomes SNP and HLA genotypes and assessed for their ability to
      accurately impute molecular HLA-A, -B, -C and -DRB1 genotypes in the Human Genome
      Diversity Project cell panel. Imputation concordance was high (>89%) across all
      methods for both HLA-A and HLA-C, but HLA-B and HLA-DRB1 proved generally
      difficult to impute. Overall, <27.8% of subjects were correctly imputed for all
      HLA loci by any method. Concordance across all loci was not enhanced via the
      application of confidence thresholds; reliance on confidence scores across
      methods only led to noticeable improvement (+3.2%) for HLA-DRB1. As the HLA
      complex is highly relevant to the study of human health and disease, a
      standardized assessment of SNP-based HLA imputation methods is crucial for
      advancing genomic research. Considerable room remains for the improvement of HLA
      B and especially HLA-DRB1 imputation methods, and no imputation method is as
      accurate as molecular genotyping. The application of large, ancestrally diverse
      HLA and SNP reference data sets and multiple imputation methods has the potential
      to make SNP-based HLA imputation methods a tractable option for determining HLA
      genotypes.

PMID- 28440343
TI  - CYP3A4 genotype is associated with sildenafil concentrations in patients with
      heart failure with preserved ejection fraction.
AB  - Despite its established inter-individual variability, sildenafil has been the
      subject of only a few pharmacogenetic investigations, with limited data regarding
      the genetic modulators of its pharmacokinetics. We conducted a pharmacogenetic
      sub-study of patients randomized to sildenafil (n=85) in the RELAX trial, which
      investigated the impact of high-dose sildenafil in patients with heart failure
      with preserved left ventricular ejection fraction (HFpEF). In the overall
      population, the CYP3A4 inferred phenotype appeared associated with the dose
      adjusted peak concentrations of sildenafil at week 12 and week 24 (adjusted
      P=0.045 for repeated measures analysis), although this P-value did not meet our
      corrected significance threshold of 0.0167. In the more homogeneous Caucasian
      subgroup, this association was significant (adjusted P=0.0165 for repeated
      measures). Hence, CYP3A4 inferred phenotype is associated with peak sildenafil
      dose-adjusted concentrations in patients with HFpEF receiving high doses of
      sildenafil. The clinical impact of this association requires further
      investigation.

PMID- 28440345
TI  - Ultrasound student education.
AB  - .

PMID- 28440344
TI  - Toxicogenomic module associations with pathogenesis: a network-based approach to
      understanding drug toxicity.
AB  - Despite investment in toxicogenomics, nonclinical safety studies are still used
      to predict clinical liabilities for new drug candidates. Network-based approaches
      for genomic analysis help overcome challenges with whole-genome transcriptional
      profiling using limited numbers of treatments for phenotypes of interest. Herein,
      we apply co-expression network analysis to safety assessment using rat liver gene
      expression data to define 415 modules, exhibiting unique transcriptional control,
      organized in a visual representation of the transcriptome (the 'TXG-MAP').
      Accounting for the overall transcriptional activity resulting from treatment, we
      explain mechanisms of toxicity and predict distinct toxicity phenotypes using
      module associations. We demonstrate that early network responses complement
      traditional histology-based assessment in predicting outcomes for longer studies
      and identify a novel mechanism of hepatotoxicity involving endoplasmic reticulum
      stress and Nrf2 activation. Module-based molecular subtypes of cholestatic injury
      derived using rat translate to human. Moreover, compared to gene-level analysis
      alone, combining module and gene-level analysis performed in sequence identifies
      significantly more phenotype-gene associations, including established and novel
      biomarkers of liver injury.

PMID- 28440346
TI  - Imaging of intrahepatic progression of hepatocellular carcinoma post
      transarterial chemoembolization. A long-term, prospective evaluation of contrast
      enhanced ultrasonography (CEUS).
AB  - AIMS: To assess the diagnostic efficacy of contrast-enhanced ultrasonography
      (CEUS) in the context of intrahepatic progression (IHP) of hepatocellular
      carcinoma (HCC) after transarterial chemoembolization (TACE). MATERIAL AND
      METHODS: Sixty HCC patients were prospectively included in the study. They were
      treated with transarterial chemoembolization (TACE)with doxorubicin-eluting
      microspheres (231 sessions). Imaging follow-up was performed 1 month after each
      session and at 3-6 month intervals after the last session of TACE and included
      CEUS and contrast-enhanced magnetic resonance (MR) imaging (reference modality).
      The diagnosis of IHP was based on mRECIST criteria and the respective findings of
      MR and CEUS were recorded, categorized and correlated. RESULTS: A total of 441
      CEUS studies were compared with the corresponding MR studies. During a follow-up
      period of 5-82 months (mean: 22 months), MR diagnosed 51 cases of IHP in 34/60
      (56.6%) patients. CEUS correctly diagnosed 12/14 (85.7%) cases of IHP of target
      tumors, 2/5 (40%) cases of IHP of non-target tumors, 13/18 (72.2%) cases of
      distal and 6/9 (66.6%) cases of proximal new lesions, and 5/5 (100%) cases of
      major vessel involvement. On a per-lesion basis, CEUS was significantly inferior
      to MR in the detection of new lesions (p=0.002). No false positive CEUS diagnoses
      of IHP were observed. 54% of the diagnostic failures of CEUS were considered
      clinically significant. CONCLUSION:  In the long term evaluation of HCC post
      TACE, CEUS appears to have limitations in the detection of IHP, which are more
      prominent in the case of new lesions and of progressive non-target tumors.

PMID- 28440347
TI  - Performance of 2D-SWE.GE for predicting different stages of liver fibrosis, using
      Transient Elastography as the reference method.
AB  - AIM: To evaluate the performance of 2D shear-wave elastography from General
      Electric (2D-SWE.GE) for the noninvasiveassessment of liver fibrosis and to
      identify liver stiffness (LS) cut-off values for predicting different stages of
      fibrosisusing Transient Elastography (TE) as the reference method. MATERIAL AND
      METHOD: We included 331 consecutive subjectswith or without chronic hepatopathies
      in whom LS was evaluated in the same session by means of 2 elastographic
      techniques:TE and 2D-SWE.GE. Reliable LS measurements were defined for TE as the
      median value of 10 measurements with a successrate of >=60% and an interquartile
      range (IQR)<30% and for 2D-SWE.GE as the median value of 10 measurements
      acquiredin a homogenous area and an IQR<30%. To discriminate between TE fibrosis
      stages we used the following cut-offs: F2- 7;F3- 9.5 and F4- 12kPa. RESULTS:
      Reliable LS measurements were obtained in 95.8% subjects by 2D-SWE.GE, and
      94.2%by TE (p=0.44). Based on TE cut-off values we divided our cohort into four
      groups: F<2: 30.1%; F=2: 10.2%; F=3: 12.2%;F=4: 47.5%. A strong correlation was
      found between the LS values obtained by the 2 methods: r=0.83, p<0.0001.LS
      valuesobtained by 2D-SWE.GE were significantly lower than those obtained by TE:
      10.14+/-4.24 kPa vs. 16.72+/-13.4 kPa (p<0.0001).The best cut-off value for F>=2,
      F>=3 and for F=4 were 6.7, 8.2 and 9.3 kPa. CONCLUSIONS: The best 2D-SWE.GE cut
      off valuesfor predicting F>=2, F>=3 and F=4 were 6.7, 8.2 and 9.3kPa.

PMID- 28440348
TI  - Diagnostic utility of endoscopic ultrasonography-elastography in the evaluation
      of solid pancreatic masses: a meta-analysis and systematic review.
AB  - AIM: The accuracy for endoscopic ultrasonography-elastography (EUS-EG) in the
      evaluation of solid pancreatic masses varies greatly and the pooled results have
      not been updated since 2013. Also, there still lack a comprehensive comparison
      among EUS-EG, contrast-enhanced EUS (CE-EUS), and EUS-guided fine needle
      aspiration (EUS-FNA).Material and methods: A thorough search was made for
      diagnostic trials investigating the role of EUS-EG in solid pancreatic masses.
      Meta-Disc was used to calculate the pooled sensitivity, specificity, diagnostic
      odds ratio and summary receiver operator characteristics. Results: Finally, 17
      studies (1537 patients, 1544 lesions) were selected. The pooled sensitivity and
      specificity for qualitative methods were 0.97 (95%CI, 0.95-0.99) and 0.67 (95%CI,
      0.59-0.74), respectively; the pooled sensitivity and specificity for strain
      histograms were 0.97 (95%CI, 0.95-0.98) and 0.67(95%CI, 0.61-0.73), respectively;
      the pooled sensitivity and specificity for strain ratio were 0.98 (95%CI, 0.96
      0.99) and 0.62 (95%CI, 0.56-0.68), respectively; the pooled sensitivity and
      specificity for CE-EUS were 0.90 (95%CI, 0.83-0.95) and 0.76 (95%CI, 0.67-0.84),
      respectively; the pooled sensitivity and specificity for EUS-FNA were 0.84
      (95%CI, 0.77-0.90) and 0.96(95%CI, 0.88-1.00), respectively. CONCLUSION: EUS-EG
      is reliable for distinguishing solid pancreatic masses; the sensitivity and
      specificity for different diagnostic methods were very close. Both EUS-EG and CE
      EUS can be valuable complementary supplements for EUS-FNA.

PMID- 28440349
TI  - Cyst-to-kidney volume ratio in the sonographic diagnosis of unilateral
      multicystic dysplastic kidney in children.
AB  - AIMS: To evaluate the usefulness of the cyst-to-kidney volume ratio determined by
      ultrasonography (US) in unilateral multicystic dysplastic kidney (MCDK) in
      children. MATERIAL AND METHODS: Our study group included 21 children (average
      age: 431 days) with unilateral MCDK and 22 children (average age: 440 days) with
      unilateral grade IV hydronephrosis due to ureteropelvic junction obstruction as
      the control group. All the children underwent transabdominal US. In children with
      MCDK, we calculated cyst-to-kidney volume ratios (volume of the largest
      cyst/volume of the MCDK) and in the control group the volume ratios of the renal
      pelvis and the largest calyx (volume of the pelvis or largest calyx/volume of the
      ipsilateral hydronephrotic kidney). Ellipsoid formula was used to calculate
      kidney and pelvis volumes. Sphere volume formula was used to calculate the
      largest cyst and calyx volumes. RESULTS: The mean cyst-to-kidney volume ratio
      (0.38+/-0.21) was significantly higher than the mean volume ratios of the renal
      pelvises (0.10+/-0.05) and the largest calyces (0.04+/-0.02) (p<0.05). There was
      no significant correlation between cyst-to-kidney volume ratio and the ages of
      the children (r=0.141, p=0.541). CONCLUSIONS:  With the aid of both the
      qualitative sonographic criteria and the newer data that we have proposed, US is
      a useful tool in the initial diagnosis of MCDK and for differentiation of MCDKs
      from grade IV hydronephrotic kidneys in children. The cyst-tokidney volume ratio
      is independent of age and thus, it can be helpful in the diagnosis of unilateral
      MCDK at any age.

PMID- 28440350
TI  - High frequency ultrasonography of the hand versus anti-RA33 evaluation in early
      rheumatoid arthritis - a pilot study.
AB  - AIM: Accurate diagnosis and early treatment in rheumatoid arthritis (RA) can lead
      to a good outcome and a correct management of the disease. We aimed toinvestigate
      the prognostic value of anti-RA33 antibodies, by evaluating the relationship with
      ultrasonographic (US) findings in patients with early RA. MATERIAL AND METHODS:
      We performed a prospective study which included 29 patients, diagnosed with early
      RA according to the ACR/EULAR 2010 criteria and 21 sex and age-matched control
      subjects. All patients underwent clinical and biological assessment, followed by
      US examination in grayscale (GS) and power Doppler (PD) at baseline and after 12
      months [from the second to the fifth metacarpophalangeal (MCP) and proximal
      interphalangeal (PIP) joints and wrists (RCC), in dorsal aspect]. The second and
      fifth MCP joints were scanned also in lateral aspects. RESULTS: The initial GS
      evaluation revealed the presence of synovitis in all 29 patients; PD found at
      least one joint with a PD grade higher than 1 in 23 patients, higher than 2 in 20
      patients, and grade 3 in 6 patients; at 12 months, we revealed the presence of
      GSUS synovitis in 25 patients and PDUS examination found active synovitis in 12
      subjects. In those patients, the anti-RA33 titre was significantly lower compared
      to those without PDUS active synovitis (p=0.031), with a moderately negative
      correlation (r=-0.519, p=0.0039). CONCLUSIONS: The current study shows that anti
      RA33 antibodies might constitute an additional tool for diagnosing early RA
      patients and can help identify patients with mild disease and a low level of
      activesynovitis.

PMID- 28440351
TI  - Characterization of benign thyroid nodules with HyperSPACE (Hyper Spectral
      Analysis for Characterization in Echography) before and after percutaneous laser
      ablation: a pilot study.
AB  - AIMS: To evaluate the capability of the HyperSPACE (Hyper SPectral Analysis for
      Characterization in Echography) method in tissue characterization, in order to
      provide information for the laser treatment of benign thyroid nodules in respect
      of conventional B-mode images and elastography. MATERIAL AND METHODS: The method,
      based on the spectral analysis of the raw radiofrequency ultrasonic signal, was
      applied to characterize the nodule before and after laser treatment. Thirty
      patients (25 females and 5 males, age between 37 and 81 years) with thyroid
      benign nodule at cytology (Thyr 2) were evaluated by conventional
      ultrasonography, elastography, and HyperSPACE, before and after laser ablation.
      RESULTS: The images processed by HyperSPACE exhibit different color distributions
      that are referred to different tissue features. By calculating the percentages of
      the color coverages, the analysed nodules were subdivided into 3 groups. Each
      nodule belonging to the same group experienced, on average, similar necrosis
      extension. The nodules exhibit different Configurations (colors) distributions
      that could be indicative of the response of nodular tissue to the laser
      treatmentConclusions: HyperSPACEcan characterize benign nodules by providing
      additional information in respect of conventional ultrasound and elastography
      which is useful for support in the laser treatment of nodules in order to
      increase the probability of success.

PMID- 28440352
TI  - Intrathyroidal ectopic thymus in children: a sonographic survey.
AB  - AIMS: Intrathyroidal ectopic thymus (IET) is being increasingly reported in the
      radiology literature. Most of the reports are of individual cases or small series
      and prevalence and natural course of the pathology is not well known. The purpose
      of this study is to establish the prevalence of IET in children and report long
      term follow-up results. MATERIAL AND METHODS: In 180 children who were examined
      by ultrasound (US) for other reasons, 7 patients were indentified with IET.
      Together with the other seven children who were already under follow-up for IET
      (diagnosed using US criteria), these 14 patients were followed up with US for 30
      months. Size, shape, location, echotexture and internal echoes of the lesions
      were evaluated. RESULTS: There were 16 lesions in 14 children. The most common
      appearance was a fusiform hypoechoic lesion, with punctate and linear internal
      echoes and well-defined but slightly irregular borders located posteriorly in the
      lower thirds of the thyroid. In follow-up, there were no changes in echotexture,
      shape or border. In 3 patients, the lesion became slightly smaller, in a 10-year
      old boy slightly larger, and in an 11-year old boy the lesion disappeared. In a
      patient with bilateral lesions, one lesion slightly decreased in size.
      CONCLUSIONS: IET in children may be more common than thought. Its growth reflects
      that of a normal thymus. Awareness of this entity is important in order not to
      misdiagnose them, especially as papillary cancer, and to prevent unnecessary
      interventions.

PMID- 28440353
TI  - The safety and feasibility of diagnostic acoustic radiation force impulse
      elastography used for eyes. A preliminary in vivo study.
AB  - AIMS: To assess the safety and feasibility of acoustic radiation force impulse
      (ARFI) elastography in the eyes of rats. Material and methods: One hundred and
      twenty-six SD rats were divided into 7 groups. Group 1 was the control group and
      Group 2 to Group 7 were investigated by ARFI elastography using increased powers
      of 5%, 10%, 20%, 50%, and 100% and repetitions of 5 or 10. The changes of ocular
      architecture structures and functions were examined by phthalmoscopic,
      histopathologic, and light reflex examination, and the expression level of IL-6,
      IL-8, and TNF-alpha was determined in days 1, 3, and 7 after ARFI elastography,
      respectively. RESULTS: A satisfactory ARFI elastography was obtained in all SD
      rats. The shear wave velocity (SWV) values of soft tissues behind the eyeball
      were significantly greater than those of the eyes (1.89+/-0.95 vs. 0.84+/-0.36
      m/s, p<0.05). The SWV values of eyes and the soft tissues behind the eyeball did
      not differ among any groups at any time-point (p>0.05). The SD rats of each group
      showed good light perception, pupillary light reflex, and avoidance reaction
      induced by the sudden bright light from the dark environment at any time. In each
      group, ocular architecture structures were well preserved, and with a normal
      expression level of IL-6, IL-8, and TNF-alpha (p>0.05). CONCLUSIONS: Diagnostic
      ARFI elastography is a safe and feasible ultrasonic imaging mode and may
      potentially be applied for human eyes in its present form.

PMID- 28440354
TI  - Normal intracranial BS/BSOB ratio values in the first trimester of single
      gestations with live fetuses in a Korean population.
AB  - AIM: The purpose of this study was to determine the normal length of the
      brainstem (BS) in Korean fetuses and to evaluatethe usefulness of the routine
      measurement of BS size in the first trimester of pregnancy for the early
      detection of spina bifida. MATERIAL AND METHODS: A total of 2,621 normal
      singleton pregnant Korean women at 10+6 to 13+6 weeks of gestation were selected
      for this retrospective cross-sectional study. Ultrasonography was used to measure
      the length of the longest vertical depth diameter of the BS and brainstem
      occipital bone (BSOB) in order to obtain the BS to BSOB ratio. RESULTS: The best
      indicators for spina bifida ranged from 1.00+/-0.24 mm to 4.70+/-0.46 mm for the
      BS and from 2.90+/-0.36 mm to 8.50+/-0.92 mm for the BSOB. For the gestational
      period, BS (R=0.70) and BSOB (R=0.81) values were considered statistically
      significant (p<.0001). The value of the BS to BSOB ratio was <1.0 in normal
      fetuses, and was not correlated with the gestational age. CONCLUSION: Measurement
      of BS and BSOB diameter in the first trimester is thought to provide the best
      reference marker for evaluating the posterior brain for diagnosis of spina
      bifida.

PMID- 28440355
TI  - Thyroid Ultrasound: State of the Art. Part 2 - Focal Thyroid Lesions.
AB  - Accurate differentiation of focal thyroid nodules (FTL) and thyroid abnormalities
      is pivotal for proper diagnostic and therapeutic work-up. In these two part
      articles, the role of ultrasound techniques in the characterization of FTL and
      evaluation of diffuse thyroid diseases is described to expand on the recently
      published World Federation in Ultrasound and Medicine (WFUMB) thyroid
      elastography guidelines and review how this guideline fits into a complete
      thyroid ultrasound exam.

PMID- 28440356
TI  - Abnormal ultrasound appearance of the amniotic membranes - diagnostic and
      significance: a pictorial essay.
AB  - The obstetrical ultrasound may identify the protrusion of the uterine surface or
      placental area into the amniotic cavity. The differential diagnosis of this
      pathology with uterine adhesions, septate uterus, circumvallate placenta,
      amniotic band or amniotic sheet can be sometimes difficult. The purpose of the
      pictorial essay is to exemplify the presence of the amniotic sheet and
      circumvallate placenta in routine obstetrics screening of all trimesters of
      pregnancy.

PMID- 28440357
TI  - Virtual hysteroscopy: a new non invasive approach for the assessment of uterine
      cavity.
AB  - Endometrial pathology is frequent in premenopausal women and the diagnostic
      hysteroscopy is considered the gold standard for assessing endometrial cavity and
      congenital uterine anomalies. However it is an invasive and uncomfortable
      procedure. Saline contrast hysterosalgingography and hysterosalpingo-contrast
      sonography allow detailed assessment of the uterine cavity. We propose a virtual
      hysteroscopy from three-dimensional saline and three-dimensional hysterosalpingo
      contrast sonography scan data to generate a virtual reality as a new noninvasive
      procedure for assessing the uterine cavity in uterine congenital anomaly and
      endometrial pathology cases as well.

PMID- 28440358
TI  - Ultrasonographic evaluation of acute pelvic pain in pregnant and postpartum
      period.
AB  - Acute pelvic pain in pregnant and postpartum patients presents diagnostic and
      therapeutic challenges. The interpretation of imaging findings in these patients
      is influenced by the knowledge of the physiological changes that occur during the
      pregnant and postpartum period, as well as by the clinical history.
      Ultrasonography remains the primary imaging investigation of the pregnant and
      postpartum women. This article describes the causes and imaging features of acute
      pelvic pain in pregnant and postpartum period and suggests characteristics to
      such diseases, focusing on the ultrasonography features that allow one to arrive
      at the corrective diagnosis. Knowledge of the clinical settings and imaging
      features of acute pelvic pain in pregnant and postpartum period can lead to
      accurate diagnosis and appropriate management of the condition.

PMID- 28440359
TI  - Ultrasonographic findings in hyperimmunoglobulin D syndrome: a case report.
AB  - Hyperimmunoglobulin D syndrome due to mevalonate kinase deficiency is a rare
      autoinflammatory disease with digestive tract involvement. We report an 11-year
      female child who has presented since the age of 1 year, bouts of fever, rash,
      joint swelling, pulmonary consolidation, lymph node involvement and
      hepatosplenomegaly. Hyperimmunglobulin D and increased urinary mevalonic acid
      were detected. The ultrasonographic features of hepatosplenomegaly ranged from
      increment in size to pseudotumoral involvement, with hypoechogenic masses without
      apparent wall. Abdominal CT during a disease flare showed hypodense,
      hypoenhancing nodular lesions, suggesting metastases. Nevertheless, a thorough
      search for malignancy was negative and the masses disappeared after the flare.
      Mevalonate kinase deficiency may add to the causes of hepatosplenic and pulmonary
      inflammatory pseudotumors.

PMID- 28440360
TI  - Anorectal malformation as a cause of recurring perineal abscesses - value of
      anorectal endosonography and magnetic resonance imaging: a case report.
AB  - Malformations of the rectum and urinary tract frequently coexist, and the
      prevalence of urogenital defects in patients with a rectal defect ranges from 20
      to 54%. In most patients, anorectal malformations are diagnosed and treated
      surgically in early childhood. In this report, we present a case of a 52-year-old
      male with a history of urological operations in infancy due to a congenital
      urethral malformation and multiple recurrent episodes of perineal abscesses with
      urinary retention. Anorectal endosonography and magnetic resonance imaging
      revealed the presence of a large cystic lesion adjacent to the rectal wall which
      became smaller at the level of the puborectalis. The walls of the lesion had a
      layered structure identical to the wall of the rectum. In addition, the
      examinations showed hypotrophy of the left lobe of the prostate and lack of left
      semnal vesicles. Thus, the lesion was diagnosed as duplication of the rectum or
      rectal diverticulum. Surgery was performed by an interdisciplinary team of
      colorectal surgeons and urologist. The lesion was removed laparoscopically. The
      pathological report revealed that the cystic wall was typical of the intestinal
      wall, consistent with a diagnosis of rectal duplication.

PMID- 28440361
TI  - The role of echocardiography in fetal tachyarrhythmia diagnosis. A burden for the
      pediatric cardiologist and a review of the literature.
AB  - Supraventricular tachyarrhythmia represents the most frequent fetal dysrhythmia.
      In the lack of diagnosis and treatment these fetuses may develop hydrops and even
      death. For the therapeutic approach it is important to establish the diagnosis of
      the type of supraventricular tachycardia. In this paper we report 29 cases with
      different types of supraventricular tachycardia in which the diagnosis was
      established using our own protocol, which allowed us to make the difference
      between the types of tachycardia (atrioventricular reentry tachycardia due to the
      accessory pathway, atrial ectopic tachycardia and permanent junctional reciprocal
      tachycardia). We acquired the data by a series of recordings in M mode and pulsed
      Doppler by simultaneous recording of an artery and a vein flow. First of all, we
      diagnosed the supraventricular tachycardia type, with short or long
      ventriculoarterial interval, and afterwards, we made the difference between
      atrial ectopic tachycardia and permanent junctional reciprocal tachycardia using
      methods to decrease the atrioventricular conduction.

PMID- 28440362
TI  - Complication of non-US guided procedure of aquafilling breast gel.
AB  - .

PMID- 28440363
TI  - Ultrasound Imaging for Posterior Knee Pain: Tibial Nerve Schwannoma Not Popliteus
      Muscle Strain.
AB  - .

PMID- 28440364
TI  - Diagnosis of an actively bleeding rectus sheath hematoma by Contrast- Enhanced
      ultrasound.
AB  - .

PMID- 28440366
TI  - Improved electrical conductivity of TPU/carbon black composites by addition of
      COPA and selective localization of carbon black at the interface of sea-island
      structured polymer blends.
AB  - The electrical percolation threshold of carbon black (CB) in thermoplastic
      polyurethane (TPU) decreases by 46% with the incorporation of 20 wt% polyamide
      copolymer (COPA) through selective localization of CB particles at the interface
      of sea-island structured TPU/COPA blends. Composites with a composition of TPU/20
      wt% COPA/9 wt% CB were prepared by four different mixing sequences and their
      morphologies were investigated by FESEM and TEM. The majority of CB particles
      were observed at the interface of sea-island structured blends irrespective of
      the compounding sequence used, although the percentage of CB particles at the
      interface is considerably less in the composite prepared by adding COPA to
      premixed TPU/CB. The driving force for the interfacial localization of most CB
      particles is the hydrogen bonding of CB with both TPU and COPA, which is
      confirmed by FTIR and DMA investigations. CB particles act like Janus particle
      type compatibilizers with bonded TPU molecules toward the TPU phase and bonded
      COPA chains toward the COPA phase. Highly efficient conductive paths are formed
      through the CB-covered domains and a short inter-domain distance.

PMID- 28440369
TI  - A variable stiffness dielectric elastomer actuator based on electrostatic
      chucking.
AB  - Dielectric elastomer actuators (DEA) are one type of promising artificial muscle;
      however, applications of bending-type DEA for robotic end-effectors may be
      limited by their low stiffness and ability to resist external loads without
      buckling. Unimorph DEA can produce large out-of-plane deformation suitable for
      use as robotic end effectors; however, design of such actuators for large
      displacement comes at the cost of low stiffness and blocking force. This work
      proposes and demonstrates a variable stiffness dielectric elastomer actuator
      (VSDEA) consisting of a plurality of unimorph DEA units operating in parallel,
      which can exhibit variable electrostatic chucking to modulate the structure's
      bending stiffness. The unimorph DEA units are additively manufactured using a
      high-resolution pneumatic dispenser, and VSDEA comprising various numbers of
      units are assembled. The performance of the DEA units and VSDEA are compared to
      model predictions, exhibiting a maximum stiffness change of 39.2*. A claw
      actuator comprising two VSDEA and weighing 0.6 grams is demonstrated grasping and
      lifting a 10 gram object.

PMID- 28440368
TI  - Mangiferin functionalized radioactive gold nanoparticles (MGF-198AuNPs) in
      prostate tumor therapy: green nanotechnology for production, in vivo tumor
      retention and evaluation of therapeutic efficacy.
AB  - We report here an innovative feature of green nanotechnology-focused work showing
      that mangiferin-a glucose functionalized xanthonoid, found in abundance in mango
      peels-serves dual roles of chemical reduction and in situ encapsulation, to
      produce gold nanoparticles with optimum in vivo stability and tumor specific
      characteristics. The interaction of mangiferin with a Au-198 gold precursor
      affords MGF-198AuNPs as the beta emissions of Au-198 provide unique advantages
      for tumor therapy while gamma rays are used for the quantitative estimation of
      gold within the tumors and various organs. The laminin receptor specificity of
      mangiferin affords specific accumulation of therapeutic payloads of this new
      therapeutic agent within prostate tumors (PC-3) of human prostate tumor origin
      induced in mice which overexpress this receptor subtype. Detailed in vivo
      therapeutic efficacy studies, through the intratumoral delivery of MGF-198AuNPs,
      show the retention of over 80% of the injected dose (ID) in prostate tumors up to
      24 h. By three weeks post treatment, tumor volumes of the treated group of
      animals showed an over 5 fold reduction as compared to the control saline group.
      New opportunities for green nanotechnology and a new paradigm of using mangiferin
      as a tumor targeting agent in oncology for the application of MGF-198AuNPs in the
      treatment of cancer are discussed.

PMID- 28440370
TI  - Structure of liquid water - a dynamical mixture of tetrahedral and 'ring-and
      chain' like structures.
AB  - The nature of the dynamical hydrogen-bond network of liquid water under ambient
      conditions has challenged both experimental and theoretical researchers for
      decades and remains a topic of intense debate. In this work, we addressed the
      structural issue of the hydrogen-bond network of liquid water based on an
      accurate ab initio molecular dynamics simulation. The present work showed clearly
      that liquid water is neither accurately described by a static picture of mostly
      tetrahedral water molecules nor dominated by "ring-and-chain" like structures.
      Instead, the structure of water is a dynamical mixture of tetrahedral and 'ring
      and-chain' like structures with a slight bias toward the former. On average, each
      water molecule forms about three hydrogen bonds with the surrounding water
      molecules. The present accurate ab initio molecular dynamics simulation of liquid
      water was made possible by using a fragment-based second-order Moller-Plesset
      perturbation theory (MP2) with a large basis set to treat a large body of water
      molecules. This level of ab initio theory is sufficiently accurate for describing
      water interactions, and the simulated structural and dynamical properties of
      liquid water, including radial distribution functions, diffusion coefficient,
      dipole moment, etc., are uniformly in excellent agreement with experimental
      observations.

PMID- 28440371
TI  - Role of uncrosslinked chains in droplets dynamics on silicone elastomers.
AB  - We report an unexpected behavior in wetting dynamics on soft silicone substrates:
      the dynamics of aqueous droplets deposited on vertical plates of such elastomers
      exhibits two successive speed regimes. This macroscopic observation is found to
      be closely related to microscopic phenomena occurring at the scale of the polymer
      network: we show that uncrosslinked chains found in most widely used commercial
      silicone elastomers are responsible for this surprising behavior. A direct
      visualization of the uncrosslinked oligomers collected by water droplets is
      performed, evidencing that a capillarity-induced phase separation occurs:
      uncrosslinked oligomers are extracted from the silicone elastomer network by the
      water-glycerol mixture droplet. The sharp speed change is shown to coincide with
      an abrupt transition in surface tension of the droplets, when a critical surface
      concentration in uncrosslinked oligomer chains is reached. We infer that a
      droplet shifts to a second regime with a faster speed when it is completely
      covered with a homogeneous oil film.

PMID- 28440372
TI  - Autonomous unimer-vesicle oscillation by totally synthetic diblock copolymers:
      effect of block length and polymer concentration on spatio-temporal structures.
AB  - In this study, factors controlling autonomous vesicle oscillations exhibited by
      self-oscillating diblock copolymers were investigated. The self-oscillating
      diblock copolymer contains poly(ethylene oxide) (PEO) as the hydrophilic block
      and a random copolymer composed of N-isopropylacrylamide (NIPAAm) with side
      chains of ruthenium tris(2,2'-bipyridine) (Ru(bpy)3), which catalyzes the
      Belousov-Zhabotinsky (BZ) reaction, as the self-oscillating block. Recently, our
      group has reported that a diblock copolymer exhibits a unique autonomous
      disintegration and reconstruction of the vesicles driven by the periodic redox
      changes of Ru(bpy)3 in a catalyst-free BZ reaction solution. Nevertheless, the
      effect of the diblock copolymer architecture on the structure of the vesicles
      under equilibrium conditions, as well as their oscillation properties under non
      equilibrium conditions, has not been clarified thus far. Hence, self-oscillating
      diblock copolymers with different block lengths were systematically synthesized,
      and the effects of the block length and polymer concentration on the spatio
      temporal vesicle structures were comprehensively discussed.

PMID- 28440374
TI  - Electrotunable lubricity with ionic liquids: the influence of nanoscale
      roughness.
AB  - The properties of ionic liquids can be modified by applying an external
      electrostatic potential, providing a route to control their performance in
      nanolubrication applications. Most computational studies to date have focused on
      the investigation of smooth surfaces. Real surfaces are generally inhomogeneous
      and feature roughness of different length scales. We report here a study of the
      possible effects that surface roughness may have on electrotunable lubricity with
      ionic liquids, performed here by means of non-equilibrium molecular dynamics
      simulations. In order to advance our understanding of the interplay of friction
      and substrate structure we investigate coarse grained models of ionic liquids
      confined in model surfaces with nanometer roughness. The friction is shown to
      depend on the roughness of the substrate and the direction of shear. For the
      investigated systems, the friction coefficient is found to increase with
      roughness. These results are in contrast with previous studies, where roughness
      induced reduction of friction was reported, and they highlight the strong
      sensitivity of the friction process to the structure of the surfaces. The
      friction force features a maximum at a specific surface charge density. This
      behaviour is reminiscent of the one reported in ionic liquids confined by flat
      surfaces, showing the generality of this physical effect in confined ionic
      liquids. We find that an increase of the substrate-liquid dispersion interactions
      shifts the maximum to lower surface charges. This effect opens a route to control
      electrotunable friction phenomena by tuning both the electrostatic potential and
      the composition of the confining surfaces.

PMID- 28440375
TI  - Correction: Cooperative strings in glassy nanoparticles.
AB  - Correction for 'Cooperative strings in glassy nanoparticles' by Maxence Arutkin
      et al., Soft Matter, 2017, 13, 141-146.

PMID- 28440376
TI  - Occurrence of perchlorate in groundwater, paired farmland soil, lettuce, and
      rhizosphere soil from Chengdu, China.
AB  - A total of 28 groundwater, paired farmland soil, lettuce, and its rhizosphere
      soil samples were collected from Chengdu, China to detect perchlorate levels and
      to evaluate the relationships of perchlorate concentrations among these matrices.
      The perchlorate concentrations in the groundwater, farmland soil, lettuce, and
      rhizosphere soil samples ranged from below detection limit to 60.2 MUg L-1, from
      below detection limit to 249 MUg kg-1 dry weight (dw), from 2.07 to 1010 MUg kg-1
      wet weight, and from below detection limit to 314 MUg kg-1 dw, respectively.
      Significant correlation was found in the perchlorate levels among the farmland
      soil, lettuce, and rhizosphere soil, suggesting that they have common pollution
      sources, or perchlorate might transfer from farmland soil-rhizosphere soil-plant.
      However, there is no significant correlation between groundwater and the other
      three matrices, indicating that infiltration from perchlorate contaminated
      farmland soil was not the predominant source for groundwater pollution in
      Chengdu. The perchlorate concentrations in the farmland soil and lettuce samples
      were significantly higher than those in the rhizosphere soil, primarily due to
      uptake of perchlorate through the rhizosphere micro-environment by lettuce, or
      accelerated degradation by rhizospheric microorganisms, which contributed more
      needs further investigation.

PMID- 28440377
TI  - Microviscosity, encapsulation, and permeability of 2-ketooctanoic acid vesicle
      membranes.
AB  - In the current work, the microviscosity, encapsulation, and permeability of 2
      ketooctanoic acid (KOCOOH) vesicle membranes were investigated by steady-state
      and time-resolved fluorescence techniques, using 1,6-diphenyl-1,3,5-hexatriene
      (DPH), riboflavin, and calcein as fluorescence probes. Our results show that the
      microviscosity of KOCOOH membranes is similar to that of common bilayer
      aggregates, the KOCOOH vesicles have the ability to encapsulate hydrophilic
      guests, and the KOCOOH membranes are permeable to ions. The permeation of OH-
      across KOCOOH membranes can be well described using a first-order kinetic model.
      The KOCOOH vesicles may be a good alternative protocell model that possesses some
      functional properties necessary for early cell membranes. To the best of our
      knowledge, this is the first report on the characteristics of vesicle membranes
      of single-tailed keto-acid amphiphiles.

PMID- 28440378
TI  - Dynamics of a multicomponent vesicle in shear flow.
AB  - We study the fully nonlinear, nonlocal dynamics of two-dimensional multicomponent
      vesicles in a shear flow with matched viscosity of the inner and outer fluids.
      Using a nonstiff, pseudo-spectral boundary integral method, we investigate
      dynamical patterns induced by inhomogeneous bending for a two phase system.
      Numerical results reveal that there exist novel phase-treading and tumbling
      mechanisms that cannot be observed for a homogeneous vesicle. In particular,
      unlike the well-known steady tank-treading dynamics characterized by a fixed
      inclination angle, here the phase-treading mechanism leads to unsteady periodic
      dynamics with an oscillatory inclination angle. When the average phase
      concentration is around 1/2, we observe tumbling dynamics even for very low shear
      rate, and the excess length required for tumbling is significantly smaller than
      the value for the single phase case. We summarize our results in phase diagrams
      in terms of the excess length, shear rate, and concentration of the soft phase.
      These findings go beyond the well known dynamical regimes of a homogeneous
      vesicle and highlight the level of complexity of vesicle dynamics in a fluid due
      to heterogeneous material properties.

PMID- 28440379
TI  - High-voltage positive electrode materials for lithium-ion batteries.
AB  - The ever-growing demand for advanced rechargeable lithium-ion batteries in
      portable electronics and electric vehicles has spurred intensive research efforts
      over the past decade. The key to sustaining the progress in Li-ion batteries lies
      in the quest for safe, low-cost positive electrode (cathode) materials with
      desirable energy and power capabilities. One approach to boost the energy and
      power densities of batteries is to increase the output voltage while maintaining
      a high capacity, fast charge-discharge rate, and long service life. This review
      gives an account of the various emerging high-voltage positive electrode
      materials that have the potential to satisfy these requirements either in the
      short or long term, including nickel-rich layered oxides, lithium-rich layered
      oxides, high-voltage spinel oxides, and high-voltage polyanionic compounds. The
      key barriers and the corresponding strategies for the practical viability of
      these cathode materials are discussed along with the optimization of electrolytes
      and other cell components, with a particular emphasis on recent advances in the
      literature. A concise perspective with respect to plausible strategies for future
      developments in the field is also provided.

PMID- 28440380
TI  - Viscosity of particulate soap films: approaching the jamming of 2D capillary
      suspensions.
AB  - We compute the effective viscosity of particulate soap films thanks to local
      velocity fields obtained by Particle Image Velocimetry (PIV) during film
      retraction experiments. We identify the jamming of these 2D capillary suspensions
      at a critical particle surface fraction (?0.84) where effective viscosity
      diverges. Pair correlation function and number of neighbors in contact or close
      to contact reveal the cohesive nature of this 2D capillary granular media. The
      experimental 2D dynamic viscosities can be predicted by a model considering
      viscous dissipation at the liquid interfaces induced by the motion of individual
      particles.

PMID- 28440381
TI  - Lyotropic meso-phase behavior of supra-molecular nanotubes with helical charge
      distribution.
AB  - We report diverse meso-phase arrangements of supra-molecular nanotubes assembled
      by ionic benzene-1,3,5-tricarboxamide (BTA) molecules in water; their transition
      pathway and equilibrium structure are controlled by the helical structure.
      Besides, the different sensitivity to the condition of initial solutions is
      revealed for the final rectangular phase and the intermediate phase.

PMID- 28440382
TI  - pH-Dependent structural diversity of a 2-pyridinemethanol Cu complex and its
      relatively strong magnetic exchange coupling via hydrogen bonding.
AB  - The diversity of the self-assembled structures of a Cu complex via hydrogen
      bonding, including a square planar unit, is reported. The Cu complex forms two
      self-assembled structures by hydrogen bonding, depending on the acidity of the
      recrystallization conditions. A linear chain structure can be produced under
      acidic conditions, and a three-dimensional network structure is observed under
      basic conditions. The linear chain structure is constructed from intermolecular
      sharing of a hydrogen atom between two 2-pyridinemethanolate units, with an OO
      distance of 2.412(1) A and an O-H-O bond angle of 170(3) degrees . The linear
      chain structure exhibits relatively strong magnetic coupling (J = -9.91(2) cm-1)
      via hydrogen bonding between Cu atoms; this coupling was also confirmed by
      electron spin resonance experiments. Thermochromic behavior was also observed for
      the complex.

PMID- 28440384
TI  - Theoretical and numerical analysis of nano-actuators based on grafted
      polyelectrolytes in an electric field.
AB  - We analyze, theoretically and by means of molecular dynamics (MD) simulations,
      the generation of mechanical force by a polyelectrolyte (PE) chain grafted to a
      plane and exposed to an external electric field; the free end of the chain is
      linked to a deformable target body. Varying the field, one can alter the length
      of the non-adsorbed (bulk) part of the chain and hence the deformation of the
      target body and the arising force. We focus on the impact of added salt on the
      magnitude of the generated force, which is especially important for applications.
      In particular, we develop a simple variational theory for the double layer formed
      near electrodes to compute the electric field acting on the bulk part of the
      chain. Our theoretical predictions agree well with the MD simulations. Next, we
      study the effectiveness of possible PE-based nano-vices, comprised of two
      clenching planes connected by PEs exposed to an external electric field. We
      analyze a novel phenomenon - two-dimensional diffusion of a nano-particle,
      clenched between two planes, and introduce a quantitative criterion for clenching
      efficiency, the clenching coefficient. It is defined as a logarithm of the ratio
      of the diffusion coefficients of a free and clenched particle. Using first a
      microscopic counterpart of the Coulomb friction model, and then a novel
      microscopic model based on surface phonons, with the vibration direction normal
      to the surface, we calculate the clenching coefficient as a function of the
      external electric field. Our results demonstrate a dramatic decrease of the
      diffusion coefficient of a clenched nano-particle for the range of parameters
      relevant for applications; this proves the effectiveness of the PE-based nano
      vices.

PMID- 28440385
TI  - Temporal viscosity modulations driven by a pH sensitive polymer coupled to a pH
      changing chemical reaction.
AB  - The Formaldehyde-Sulfite (FS) and the Formaldehyde-Sulfite-Gluconolactone (FSG)
      systems are examples of complex chemical reactions accompanied by well-controlled
      variations in pH. While the FS system exhibits a clock behavior, in the FSG
      reaction, this mechanism is coupled with the hydrolysis of the gluconolactone
      which gives the possibility to show large temporal oscillations of pH in an open
      reactor. In this work, we show how these reactive systems, due to their organic
      nature, can be coupled with pH sensitive polymers, particularly with polyacrylic
      acid (PAA) to trigger temporal changes of viscosity. We characterize this coupled
      reactive system showing the effects of changes in the initial concentrations of
      the polymer and in the chemical reagents on the induction time, the magnitude of
      the pH variations and the temporal modifications of the viscosity.

PMID- 28440386
TI  - Effect of chemical structure of S-nitrosothiols on nitric oxide release mediated
      by the copper sites of a metal organic framework based environment.
AB  - The effect of chemical structure of different biologically compatible S
      nitrosothiols on the solvation environment at catalytic copper sites in a metal
      organic framework (MOF) suspended in a solution of ethanol is probed using
      computational methods. The use of a copper based MOF as a storage vehicle and
      catalyst (copper sites of the MOF) in the controlled and sustained release of
      chemically stored nitric oxide (NO) from S-nitrosocysteine has been shown to
      occur both experimentally and computationally [J. Am. Chem. Soc., 2012, 134, 3330
      3333; Phys. Chem. Chem. Phys., 2015, 17, 23403]. Previous studies on a copper
      based MOF, namely HKUST-1, concluded that modifications in the R-group of s
      nitrosothiols and/or organic linkers of MOFs led to a method capable of
      modulating NO release. In order to test the hypothesis that larger R-groups slow
      down NO release, four different RSNOs (R = cysteine, N-acetylcysteine, N-acetyl
      d,l-penicillamine or glutathione) of varying size were investigated, which in
      turn required the use of a larger copper based MOF. Due to its desirable copper
      centers and more extensive framework, MOF-143, an analog of HKUST-1 was chosen to
      further explore both the effect of different RSNOs as well as MOF environments on
      NO release. Condensed phase classical molecular dynamics simulations are utilized
      to study the effect of the complex MOF environment as well as the chemical
      structure and size of the RSNO on the species on the catalytic reaction. The
      results indicate that in addition to the size of the RSNO species and the organic
      linkers within the MOF, the reaction rates can be modulated by the molecular
      structure of the RSNO and furthermore combining different RSNO species can also
      be used to tune the rate of NO release.

PMID- 28440387
TI  - Thermal bending coupled with volume change in liquid crystal gels.
AB  - We investigate the thermal bending behavior of liquid crystal gels with hybrid
      alignment (H-LCGs) accompanied by volume change in isotropic and nematic
      solvents. The curvature (r-1) of H-LCGs in each solvent markedly depends on the
      temperature (T) in the nematic state including the reversal of the bending
      direction, as in the case of the corresponding elastomers in the dry state (H
      LCE). The thermal bending of three systems-H-LCGs in isotropic and nematic
      solvents and H-LCE-differs significantly in several aspects including the T range
      where r-1 depends on T and the total variation of r-1. The differences in these
      features among the three systems result from the differences in the magnitude as
      well as the T-dependence of the nematic order (S), which is correlated with the T
      induced volume change. We demonstrate that the T-dependence of the reduced
      curvature in each system is satisfactorily described by a combination of linear
      bending theory and the anisotropic Gaussian network model using the corresponding
      S-T data.

PMID- 28440388
TI  - Formation of exceptionally weak C-C bonds by metal-templated pinacol coupling.
AB  - The ability of the bis(imidazolyl)ketone ligand BMdiPhIK (bis(1-methyl-4,5
      diphenylimidazolyl)ketone) to function as a redox active ligand has been
      investigated. The reduction of [M(BMdiPhIK)Cl2] (M = Fe and Zn) complexes
      resulted in a pinacol-type coupling to form dinuclear complexes featuring very
      weak and abnormally elongated C-C bonds (1.729(5) and 1.708(3) A for Fe and Zn,
      respectively). Oxidation of these complexes using ferrocenium in the presence of
      Cl- ions regenerated the original [M(BMdiPhIK)Cl2] complexes, showing the
      reversibility of the coupling process. This makes it a potentially interesting
      approach for the storage of electrons and application of the BMdiPhIK ligand as a
      redox active ligand.

PMID- 28440389
TI  - Thermal behaviour of LixMeO2 (Me = Co or Ni + Mn + Co) cathode materials.
AB  - Thermal behaviour and thermophysical properties of two typical cathodes for
      lithium-ion batteries were studied in dependence of temperature. The cathode
      materials are composite thick films containing a mixture of 90 wt% LiMeO2 active
      material (with Me = Co or Me = Ni + Mn + Co, respectively) and additives (binder
      and carbon black), deposited on aluminium current collector foils. The thermal
      conductivity of each cathode type and their corresponding composite layers were
      determined up to 573 K from the measured thermal diffusivity, the specific heat
      capacity and the estimated density based on metallographic methods and structural
      investigations. In addition, the impact of lithiation degree x in LixMeO2 on the
      transport properties of cathode samples was also investigated. The quantitative
      determination and the homogeneity of Li content on the surface and within the
      bulk of the samples were validated by laser induced breakdown spectrometry. The
      results presented here explain at cell component level, i.e. cathode material,
      the thermal runaway behaviour of lithium-ion batteries in a combined approach of
      application oriented and fundamental research. Therefore, these data are
      significant for improving the simulation studies of their thermal management, in
      which the bulk properties are assumed, as a common approach, temperature and
      lithiation degree independent.

PMID- 28440391
TI  - Dehydrogenation induced inhibition of intramolecular charge transfer in
      substituted pyrazoline analogues.
AB  - The detailed photophysics of (E)-1,5-diphenyl-3-styryl-4,5-dihydro-1H-pyrazole
      (DSDP) and (E)-1,5-diphenyl-3-styryl-1H-pyrazole (DSP) has been investigated and
      compared to demonstrate the drastic modification of the photophysics upon
      dehydrogenation of the pyrazoline ring. While DSDP gives dual absorption and dual
      emission bands corresponding to the locally excited (LE) and the intramolecular
      charge transfer (ICT) species, DSP yields single absorption and emission bands
      for the locally excited species only. Comparative steady state and time resolved
      fluorometric studies reveal that aromatization of the pyrazoline ring inhibits
      the formation of the ICT species. Quantum chemical calculations corroborate and
      rationalize the inhibition of the ICT process upon aromatization through
      depiction of the differential electronic distributions in the highest occupied
      molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the
      two fluorophores.

PMID- 28440392
TI  - Suppressive role of diallyl trisulfide in the activated platelet-mediated
      hematogenous metastasis of MDA-MB-231 human breast cancer cells.
AB  - Accumulating evidence has indicated that garlic consumption may reduce the risk
      of developing several types of cancer, and extensive studies have revealed the
      effects of its bioactive component, diallyl trisulfide (DATS), on the
      proliferation and apoptosis of tumor cells. The present study was undertaken to
      examine whether DATS affects hematogenous metastasis. In view of the dynamic
      crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we
      attempted to demonstrate the role of DATS in the metastatic behavior of MDA-MB
      231 human breast cancer cells, which were co-incubated with activated platelets.
      Indeed, our data indicated that DATS significantly blocked platelet activation
      and aggregation induced by platelet-activating factor (PAF), and decreased the
      production of thromboxane B2 (TXB2). It was also found that DATS suppressed the
      migration and invasion of MDA-MB-231 cells in the presence of platelets activated
      by PAF in vitro in a dose-dependent manner. Furthermore, our results revealed
      thaat the release of activated TGF-beta1 in the platelet-tumor cell system was
      markedly attenuated by DATS. Therefore, our findings strongly suggest that the
      diverse pharmacological activities of DATS are at least partially reflected by
      the interruption of the activated platelets-mediated metastasis of breast cancer
      cells.

PMID- 28440393
TI  - Identification of key genes associated with Schmid-type metaphyseal
      chondrodysplasia based on microarray data.
AB  - This study aimed to gain a better understanding of the molecular circuitry of
      Schmid-type metaphyseal chondrodysplasia (SMCD), and to identify more potential
      genes associated with the pathogenesis of SMCD. Microarray data from GSE72261
      were downloaded from the NCBI GEO database, including collagen X p.Asn617Lys
      knock-in mutation (ColXN617K), ablated XBP1 activity (Xbp1CartDeltaEx2), compound
      mutant (C/X), and wild-type (WT) specimens. Differentially expressed genes (DEGs)
      were screened in Xbp1 vs. WT, Col vs. WT and CX vs. WT, respectively. Pathway
      enrichment analysis of these DEGs was performed. Transcription factors (TFs) of
      the overlapping DEGs were identified. Weighted correlation network analysis
      (WGCNA) was performed to find modules of DEGs with high correlations, followed by
      gene function analysis and a protein-protein interaction network construction. In
      total, 481, 1,530 and 1,214 DEGs were identified in Xbp1 vs. WT, Col vs. WT and
      CX vs. WT, respectively. These DEGs were enriched in different pathways, such as
      extracellular matrix (ECM)-receptor interaction and metabolism-related pathways.
      A total of 7 TFs were found to regulate 19 common upregulated genes, and 4 TFs
      were identified to regulate 21 common downregulated genes. Two significant gene
      co-expression modules were enriched and DEGs in the 2 modules were mainly
      enriched in different biological processes, such as ribosome biogenesis.
      Moreover, Kras (downregulated), Col5a1 (upregulated) and Furin (upregulated) were
      both identified in the regulatory networks and protein-protein interaction (PPI)
      network. On the whole, our findings indicate that the Kras, Col5a1 and Furin
      genes may play essential roles in the molecular mechanisms of SMCD, which
      warrants further investigation.

PMID- 28440394
TI  - G-protein-coupled receptor 30 mediates the effects of estrogen on endothelial
      cell tube formation in vitro.
AB  - The placenta is the exchange organ between the mother and the fetus. The
      inadequate function of this organ is associated with a number of pregnancy
      disorders. Hypoxia and oxidative stress during placental development may induce
      endothelial dysfunction, resulting in the reduction in the perfusion of the
      placenta. During pregnancy, the levels of estrogen are increased. Decreased
      estrogen levels have been reported in women with preeclampsia. However, whether
      estrogen is involved in placental angiogenesis remains unclear. In this study, we
      aimed to investigate the effects of estrogen on endothelial cell tube formation
      and to elucidate the underlying mechanisms. For this purpose, human umbilical
      vein endothelial cells (HUVECs) were cultured with 17-beta-estradiol under
      conditions of hypoxia/reoxygenation (H/R). The total pipe length of the tube-like
      structure on endothelial cells was measured. The expression levels of G-protein
      coupled receptor 30 (GPR30) and endothelial nitric oxide synthase (eNOS) and Akt
      were also measured in the endothelial cells following treatment with 17-beta
      estradiol under H/R conditions by western blot analysis and immunostaining. We
      found that the total pipe length of the tube-like structure on endothelial cells
      was significantly reduced. This reduction was reversed by treatment with 17-beta
      estradiol. The expression of GPR30 in endothelial cells was significantly
      increased following treatment with 17-beta-estradiol under H/R conditions.
      Furthermore, the levels of eNOS and Akt in endothelial cells were also
      significantly increased following treatment with 17-beta-estradiol under H/R
      conditions. The activation of eNOS was inhibited by wortmannin, an inhibitor of
      PI3K/Akt. Our data thus demonstrate that estrogen prevents the failure of
      endothelial cell tube formation induced by H/R. GPR30 plays an important role in
      these protective effects through the activation of eNOS and Akt in endothelial
      cells. Our data suggest that increased levels of estrogen are important for
      placental angiogenesis.

PMID- 28440395
TI  - MicroRNA-mediated inflammatory responses induced by Cryptococcus neoformans are
      dependent on the NF-kappaB pathway in human monocytes.
AB  - Cryptococcosis is a significant invasive fungal infection with noteworthy
      morbidity and mortality that is usually caused by either Cryptococcus neoformans
      (C. neoformans) or Cryptococcus gattii (C. gattii). Epidemiological studies have
      indicated that C. neoformans are more often reported in immunocompromised and
      immunocompetent patients. It has been well established that the cytokine profile
      of the host markedly affects the outcome of cryptococcal disease, and the
      negative regulators of microRNAs(miRs or miRNAs) are critically important for
      immunomodulation. However, the role of miRNAs and the molecular basis of the
      inflammatory response induced by C. neoformans in monocytes remain unknown. In
      this study, we identified 7 differentially expressed miRNAs in THP-1 cells
      exposed to C. neoformans by Illumina sequencing, and confirmed our findings by RT
      qPCR. Furthermore, miR-146a was selected for further analysis to identify the
      regulatory mechanisms of inflammation induced by C. neoformans. An examination of
      the function of miR-146a in monocytes was performed by overexpressing and
      inhibiting miR-146a. In addition, we identified a pattern of induction in
      response to a variety of microbial components and pro-inflammatory cytokines. Our
      data suggested that the nuclear factor-kappaB (NF-kappaB) pathway was required
      for the induction of miR-146a, whereas miR-146a negatively regulated NF-kappaB
      activation by targeting interleukin-1 receptor-associated kinase 1 (IRAK1) and
      TNF receptor associated factor 6 (TRAF6), then inhibiting NF-kappaB activation
      and the release of inflammatory cytokines in monocytes induced by C. neoformans.

PMID- 28440396
TI  - Downregulation of miR-10b promotes osteoblast differentiation through targeting
      Bcl6.
AB  - MicroRNAs (miRNAs or miRs) have been shown to play a critical role in osteoblast
      differentiation. miR-10b has been found to be downregulated during osteoblast
      differentiation; however, its precise effect on osteoblast differentiation
      remains unknown. In this study, we aimed to investigate the potential role of miR
      10b and the potential underlying mechanism in regulating osteoblast
      differentiation. We found that miR-10b was downregulated during osteoblast
      differentiation. Overexpression of miR-10b inhibited osteoblast differentiation,
      whereas the suppression of miR-10b promoted osteoblast differentiation.
      Bioinformatics analysis and the dual-luciferase reporter assay demonstrated that
      miR-10b could target the 3'-untranslated regions of B cell lymphoma 6 (Bcl6)
      which is an important regulator of osteoblast differentiation. Real-time
      quantitative polymerase chain reaction and western blot analysis showed that miR
      10b directly regulated Bcl6 expression. Further experiments showed that the
      overexpression of miR-10b increased the expression of signal transducer and
      activator of transcription 1 (STAT1) and blocked Runt-related transcription
      factor 2 (Runx2) nuclear translocation, whereas miR-10b suppression showed an
      opposite effect. Moreover, the miR-10b suppression-induced effects were partially
      reversed by Bcl6 knockdown. Taken together, our study suggests that miR-10b
      contributes to osteoblast differentiation through targeting Bcl6, providing a
      novel insight into understanding the molecular mechanism underlying osteoblast
      differentiation and suggesting a potential target for inhibiting bone loss.

PMID- 28440397
TI  - Hypermethylation of miRNA-589 promoter leads to upregulation of HDAC5 which
      promotes malignancy in non-small cell lung cancer.
AB  - Histone deacetylases (HDACs) are crucial for regulating chromatin activity, which
      plays a critical role in cell proliferation, differentiation, and apoptosis of
      various cancers. Therefore, HDAC inhibitors have been applied as effective
      therapeutic agents for cancer treatment. However, the expression profiles and
      regulatory mechanisms of histone deacetylases in lung cancer are not well
      understood. In the present study, aberrant high levels of HDAC5 were observed in
      non-small cell lung cancer (NSCLC) and further analysis indicated a negative
      relationship between HDAC5 and a tumor suppressor, miR-589-5p, in NSCLC
      specimens. Consistently, miR-589-5p reduced the expression of HDAC5 by targeting
      the 3'UTR of HDAC5 mRNA in NSCLC cells. Considering the loss of miR-589-5p in
      NSCLC, the methylation status of the miR-589 gene promoter was examined. The
      hypermethylation of the miR-589 gene promoter was more significant in NSCLC cells
      compared with lung epithelial cells, and methylation inhibition by 5-aza-2
      deoxycytidine (5-Aza-dC) decreased HDAC5 expression. Furthermore, several
      downstream gene clusters of HDAC5 were studied in the present investigation. As a
      result, miR-589-5p/HDAC5 pathway was found to regulate a number of cell cycle and
      epithelial-mesenchymal transition (EMT)-related genes in NSCLC cells. In vitro
      and in vivo phenotype experiments revealed a critical role of miR-589-5p/HDAC5
      pathway in the migration, invasion, and tumorigenicity of NSCLC cells. These
      findings demonstrate a novel mechanism for deregulation of HDAC5 in NSCLC and
      suggest that miR-589-5p/HDAC5 pathway may represent a new prognostic biomarker
      and therapeutic target against NSCLC.

PMID- 28440398
TI  - Lycopene inhibits NF-kappaB activation and adhesion molecule expression through
      Nrf2-mediated heme oxygenase-1 in endothelial cells.
AB  - The endothelial expression of cell adhesion molecules plays a leading role in
      atherosclerosis. Lycopene, a carotenoid with 11 conjugated double bonds, has been
      shown to have anti-inflammatory properties. In the present study, we demonstrate
      a putative mechanism for the anti-inflammatory effects of lycopene. We
      demonstrate that lycopene inhibits the adhesion of tumor necrosis factor alpha
      (TNFalpha)-stimulated monocytes to endothelial cells and suppresses the
      expression of intercellular cell adhesion molecule-1 (ICAM-1) at the
      transcriptional level. Moreover, lycopene was found to exert its inhibitory
      effects by blocking the degradation of the inhibitory protein, IkappaBalpha,
      following 6 h of pre-treatment. In TNFalpha-stimulated endothelial cells, nuclear
      factor-kappaB (NF-kappaB) nuclear translocation and transcriptional activity were
      abolished by up to 12 h of lycopene pre-treatment. We also found that lycopene
      increased the intracellular glutathione (GSH) level and glutamate-cysteine ligase
      expression. Subsequently, lycopene induced nuclear factor-erythroid 2 related
      factor 2 (Nrf2) activation, leading to the increased expression of downstream of
      heme oxygenase-1 (HO-1). The use of siRNA targeting HO-1 blocked the inhibitory
      effects of lycopene on IkappaB degradation and ICAM-1 expression. The inhibitory
      effects of lycopene thus appear to be mediated through its induction of Nrf2
      mediated HO-1 expression. Therefore, the findings of the present study indicate
      that lycopene suppresses the activation of TNFalpha-induced signaling pathways
      through the upregulation of Nrf2-mediated HO-1 expression.

PMID- 28440400
TI  - Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer
      through apoptosis induction.
AB  - Carnosic acid is a phenolic diterpene with anti-inflammation, anticancer, anti
      bacterial, anti-diabetic, as well as neuroprotective properties, which is
      generated by many species from Lamiaceae family. Fisetin (3,3',4',7
      tetrahydroxyflavone), a naturally flavonoid is abundantly produced in different
      vegetables and fruits. Fisetin has been reported to have various positive
      biological effects, including anti-proliferative, anticancer, anti-oxidative and
      neuroprotective effects. Lung cancer is reported as the most common neoplasm in
      human world-wide. In the present study, the possible benefits of carnosic acid
      combined with fisetin on lung cancer in vitro and in vivo was explored. Carnosic
      acid and fisetin combination led to apoptosis in lung cancer cells. Caspase-3
      signaling pathway was promoted in carnosic acid and fisetin co-treatment, which
      was accompanied by anti-apoptotic proteins of Bcl-2 and Bcl-xl decreasing and pro
      apoptotic signals of Bax and Bad increasing. The death receptor (DR) of tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) was enhanced in
      carnosic acid and fisetin combined treatment. Furthermore, the mouse xenograft
      model in vivo suggested that carnosic acid and fisetin combined treatment
      inhibited lung cancer growth in comparison to the carnosic acid or fisetin
      monotherapy. This study supplies a novel therapy to induce apoptosis to inhibit
      lung cancer through caspase-3 activation.

PMID- 28440399
TI  - alpha1-antitrypsin promotes lung adenocarcinoma metastasis through upregulating
      fibronectin expression.
AB  - alpha1-antitrypsin (AAT) has been recognized to be associated with lung
      adenocarcinoma metastasis. However, the mechanisms by which AAT promotes tumor
      metastasis remain to be investigated. Herein, we first examined AAT expression in
      a panel of formalin-fixed paraffin-embedded tumor tissues from 88 lung
      adenocarcinoma patients undergoing curative resection, using immunohistochemical
      methods. Lung adenocarcinoma patients with high AAT expression showed a
      significantly shorter overall survival compared to those with low AAT expression
      by Kaplan-Meier method (P=0.008). High AAT expression was also identified as an
      independent prognostic factor by Cox regression analysis (adjusted hazard ratio:
      2.05; P=0.04). Second, the role of AAT in lung adenocarcinoma cell migration was
      evaluated in vitro using wound healing and Transwell assays, by transfecting the
      lentivirus vector with interfering sequence or coding sequence of AAT. The
      migration property of A549 and SPC-A1 cells was significantly diminished by
      downregulating AAT expression. Conversely, the migration of both cell lines was
      significantly increased through upregulating AAT. Furthermore, AAT could increase
      the expression of fibronectin (FN). FN down-regulation reversed AAT-induced
      promotion of adenocarcinoma cell migration. Third, a cancer cell/endothelial cell
      co-culture model was established to investigate the effect of AAT on
      adenocarcinoma cell adhesion using immunofluorescence examination. The results
      showed that downregulation of AAT inhibited adhesion between lung adenocarcinoma
      cells and human umbilical vein endothelial cells whereas upregulation of AAT
      promoted adhesion, which may attribute to interactions between FN and integrin
      alpha5. Finally, AAT also showed the regulation effect on the metastatic behavior
      of lung adenocarcinoma cells in a mouse model, which may be through regulating FN
      expression. This study suggested that high AAT expression might be a negative
      prognostic marker for lung adenocarcinoma. AAT promoted lung adenocarcinoma
      metastasis, whose functional target may be FN. Our findings provide new insight
      into the mechanisms of lung adenocarcinoma metastasis.

PMID- 28440401
TI  - Relationship between T-cell receptor beta chain sequences and human
      cytomegalovirus infection in allogeneic hematopoietic stem cell transplant
      recipients.
AB  - In the present study, clonal amplifications of T-cell receptor beta variable (TCR
      BV) linked to human cytomegalovirus (HCMV) infection were detected in recipients
      of allogeneic hematopoietic stem cell transplants (HSCT), and certain
      relationships between them were identified. Furthermore, the relationship between
      TCR BV sequences and HCMV infections was investigated. The results indicated that
      the 3 recipients of HSCT had monoclonal expansion of specific TCR BV clones
      following HSCT. Among these recipients, 2 suffered from pp65 and immediate early
      (IE) antigenemia. These patients demonstrated preferential expansion of TCR BV9
      (QVRGGTDTQ) and TCR BV11 (VATDFQ). The remaining recipient did not express TCR
      BV9 and TCR BV11, nor did this individual have pp65 and IE antigenemia. These
      results suggest that expression of TCR BV9 and TCR BV11 may be associated with
      HCMV antigenemia, and may be involved in the immune response. The amino acid
      sequences 'QVRGGTDTQ' and 'VATDFQ' may be involved in HCMV reactivation in
      patients who have undergone HSCT. Assessment of the TCR BV families may provide
      valuable insight into HCMV pathogenesis and may aid in the diagnosis and therapy
      for HSCT recipients infected with HCMV.

PMID- 28440402
TI  - ERK5 regulates tobacco smoke-induced urocystic epithelial-mesenchymal transition
      in BALB/c mice.
AB  - Tobacco smoke (TS) is an important risk factor of bladder cancer. Epithelial
      mesenchymal transition (EMT) is involved in the initiation and development of
      cancer. The role of extracellular signal-regulated kinase (ERK) 5 in regulating
      TS-induced EMT remains to be elucidated. The aim of the present study was to
      investigate the regulatory role of ERK5 in TS-triggered EMT in the bladder of
      mice. BALB/c mice were used for an in vivo TS exposure model. Mice were treated
      for 6 h a day for 12 weeks. The results demonstrated that mice exposed to TS had
      decreased mRNA and protein expression levels of the epithelial markers E-cadherin
      and zonula occludens-1, whereas expression levels of the mesenchymal markers
      Vimentin and N-cadherin were increased. Treatment with XMD8-92, a highly specific
      ERK5 inhibitor, effectively abrogated TS-triggered activation of ERK5, activator
      protein-1 and EMT alterations in the bladder of BALB/c mice. The data suggested
      that ERK5 regulates TS-mediated urocystic EMT. These findings provide insight
      into the molecular mechanisms of TS-associated bladder tumorigenesis.

PMID- 28440403
TI  - Ginsenoside Rh2 and Rg3 inhibit cell proliferation and induce apoptosis by
      increasing mitochondrial reactive oxygen species in human leukemia Jurkat cells.
AB  - Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive
      components in Panax ginseng. The present study aimed to investigate the
      underlying mechanisms of apoptotic cell-death induced by GRh2 and GRg3 in human
      leukemia Jurkat cells. The Cell Counting kit-8 assay was used to determine cell
      proliferation. Apoptosis was detected by nuclear morphologic observation by
      Hoechst 33342 staining and Annexin V-allophycocyanin and 7-amino-actinomycin D
      assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was
      used to examine the effects of mitochondrial ROS on cell viability and
      mitochondrial membrane potential (MMP). Finally, the expression levels of
      numerous mitochondrial-associated apoptosis proteins were assessed by western
      blot analysis. These results demonstrated that GRh2 and GRg3 inhibited cell
      growth and induced apoptosis, and that GRh2 had greater cytotoxicity than GRg3.
      GRh2 induced generation of more mitochondrial ROS compared with GRg3 in Jurkat
      cells; however, this effect was ameliorated by subsequent treatment with
      mitoTEMPO. Furthermore, excess mitochondrial ROS induced by GRh2 was more potent
      than GRg3 in inhibiting cell proliferation and reducing MMP. In addition,
      expression levels of apoptosis-associated proteins were significantly increased
      in Jurkat cells treated with GRh2 than GRg3. In conclusion, these findings
      suggested that GRh2 and GRg3 induce mitochondrial-associated apoptosis by
      increasing mitochondrial ROS in human leukemia Jurkat cells. GRh2 may more
      effectively inhibit cell growth and accelerate apoptosis than GRg3. This study
      provides a potential novel strategy for the treatment of acute lymphoblastic
      leukemia.

PMID- 28440404
TI  - Troxerutin protects against diabetic cardiomyopathy through NF-kappaB/AKT/IRS1 in
      a rat model of type 2 diabetes.
AB  - Troxerutin is a bioflavonoid, which can be used to treat venous disorders,
      thrombosis and cerebrovascular diseases. Recent studies have demonstrated that it
      may also be used to prevent edemas. However, it is not known whether troxerutin
      protects against the cardiomyopathic complications of diabetes. In the present
      study, a rat model of type 2 diabetes was used to investigate the potential for
      troxerutin to protect against diabetic cardiomyopathy, through changes to nuclear
      factor-kappaB (NF-kappaB) expression. Troxerutin administration significantly
      reduced heart rate, blood pressure, blood glucose and plasma triglyceride levels
      across all measured time points. Furthermore, troxerutin significantly reduced
      reactive oxygen species levels, NF-kappaB protein expression, and suppressed the
      phosphorylated forms of AKT, insulin receptor substrate 1 (IRS1) and c-Jun N
      terminal kinase (JNK). These results suggested that troxerutin protects against
      cardiomyopathy via alterations in NF-kappaB, AKT and IRS1 signaling, in a rat
      model of type 2 diabetes.

PMID- 28440405
TI  - Copy-number variation analysis in familial nonsyndromic congenital anomalies of
      the kidney and urinary tract: Evidence for the causative role of a transposable
      element-associated genomic rearrangement.
AB  - Most congenital anomalies of the kidney and urinary tract (CAKUT) are sporadic,
      but familial occurrence has been described, suggesting a genetic contribution.
      Copy-number variations (CNVs) were detected in patients with CAKUT to identify
      possible novel genomic regions associated with CAKUT. CNVs were investigated in 7
      children with CAKUT from three unrelated families using array comparative genomic
      hybridization: female monozygotic twins with bilateral duplex collecting
      system/vesicoureteral reflux (VUR)/unilateral renal hypodyspasia (URHD); two male
      siblings with VUR/URHD; 3 male second cousins, one with bilateral VUR/URHD, one
      with bilateral VUR and one with ureterovesical junction obstruction (UVJO). Five
      patients had a normal constitution of CNVs, one had a duplication of 0.2 Mb on
      the 5q-arm (5q23.3), probably unrelated to CAKUT, and one with UVJO had a 1.4 Mb
      deletion on the 17q-arm (17q12) which includes a known CAKUT gene, HNF1B. The
      phenotype of HNF1B deletion was extended including renal magnesium wasting. A
      higher coverage in transposable elements (TEs) was found in the deleted region
      compared with the expected density in any random genomic region. Notably, the 5'
      breakpoint was mapped within a solo long terminal repeat (LTR) sequence.
      Moreover, highly similar members of solo LTR and mammalian interspersed
      repetitive (MIR) elements, as well as nucleotide sequence microhomology were
      detected at the breakpoint regions. In conclusion, the deletion detected in one
      patient suggests this genomic imbalance as causative for UVJO. A not very well
      known phenotype of HNF1B deletion resulting in both low urinary tract
      malformations and renal wasting of magnesium was described. The high load in TEs
      of the deleted region, the presence of highly similar elements, and the
      microhomology found at breakpoint regions may have contributed to the generation
      of the deletion. CNV analysis could reveal novel causative genomic regions in
      patients with CAKUT, and further studies in larger cohorts are needed.

PMID- 28440406
TI  - Associations of maternal PLA2G4C and PLA2G4D polymorphisms with the risk of
      spontaneous preterm birth in a Chinese population.
AB  - Preterm birth is the leading cause of mortality and morbidity in infants. Its
      etiology is multifactorial with genes and immune homeostasis. The authors
      investigated whether prostaglandin (PG) synthesis related single nucleotide
      polymorphisms (SNPs) PLA2G4C rs1366442 and PLA2G4D rs4924618 were associated with
      the risk of spontaneous preterm birth (SPTB) in a Chinese population of 114 cases
      of SPTB and 250 controls of term delivery. The risk associations were determined
      by odds ratios (ORs) and their 95% confidence intervals (CIs) calculated using
      multivariate logistic regression. Homology modeling was performed to elucidate
      potential mechanism of the SNP function. The maternal AT/TT genotype of PLA2G4D
      rs4924618 was associated with a reduced risk of SPTB (OR, 0.61; 95% CI, 0.37
      0.99), while no significant association between PLA2G4C rs1366442 and SPTB risk
      was identified. Structure and sequence analysis revealed that the amino acid
      substitution introduced by this SNP located at the conserved central core of the
      catalytic domain of cytosolic phospholipase A2 delta and was close to the active
      site. These findings suggested that the polymorphism of PLA2G4D rs4924618 may
      have a protective influence on the SPTB susceptibility in a Chinese population,
      supporting a role for genetics in the association between PG synthesis and
      preterm birth.

PMID- 28440407
TI  - Effects of cytochrome P450 family 3 subfamily A member 5 gene polymorphisms on
      daunorubicin metabolism and adverse reactions in patients with acute leukemia.
AB  - The present study aimed to investigate the association between the genetic
      polymorphism of cytochrome P450 family 3 subfamily A member 5 (CYP3A5) and the
      activity of CYP3A and plasma concentrations of daunorubicin (DNR) in patients
      with acute leukemia. A total of 36 children with newly diagnosed acute
      lymphoblastic leukemia were enrolled in the study. Polymerase chain reaction
      (PCR)-restriction fragment length polymorphism and PCR product sequencing were
      used to detect the genotype of CYP3A5*3. PCR was then used to express the mRNA
      expression of CYP3A5. A midazolam probe method was used to detect CYP3A enzyme
      activity, and DNR concentrations were measured using high performance liquid
      chromatography. Children with different genotypes had different mRNA expression
      levels of CYP3A5, and CYP3A enzyme activity in children with the CYP3A5*1 allele
      was higher, compared with that in children with the CYP3A5*3 allele. In addition,
      the area under the curve (AUC)0-24 h and AUC0-infinity of DNR were significantly
      different in children with different genotypes, however, no statistically
      significant differences were found in half-life or maximum concentration. The AUC
      of DNR was increased in children with acute lymphatic leukemia who suffered from
      cardiotoxicity, compared with those in the normal group. The CYP3A5*3 gene
      polymorphism was closely associated with the mRNA expression of CYP3A5, CYP3A
      enzyme activity and DNR plasma drug concentration, and exhibited different drug
      adverse reactions.

PMID- 28440408
TI  - Identification of potential gene targets in systemic vasculitis using DNA
      microarray analysis.
AB  - The present study aimed to identify the involvement of critical genes in systemic
      vasculitis, to gain an improved understanding of the molecular circuity and to
      investigate novel potential gene targets for systemic vasculitis treatment. The
      dual-color cDNA microarray data of GSE16945, consisting of peripheral mononuclear
      blood cell specimens from 13 patients with systemic vasculitis and 16 healthy
      controls, was downloaded from the Gene Expression Omnibus database.
      Differentially expressed genes (DEGs) were screened in systemic vasculitis
      compared with controls using BRB ArrayTools, followed by the construction of a
      protein-protein interaction (PPI) network using the clusterProfiler package, and
      significant functional interaction (FI) module selection. Furthermore,
      transcriptional factors (TFs) among the identified DEGs were predicted and a
      transcriptional regulation network was constructed. A total of 173 up- and 93
      downregulated genes were identified, which were mainly associated with immune
      response pathways. FBJ murine osteosarcoma viral oncogene homolog (FOS),
      ubiquitin B (UBB), signal transducer and activator of transcription 1 (STAT1) and
      MX dynamin-like GTPase 1 (MX1) were identified as hub proteins in the PPI
      network. Furthermore, UBB, FOS, and STAT1 were hub proteins in the three
      identified FI modules, respectively. In total, nine TFs were predicted among the
      DEGs. Of the DEGs that were predicted to be TFs, STAT1, v-maf avian
      musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) and tyrosine 3
      monooxygenase/tryptophan 5-monooxygenase activation protein Z (YWHAZ), which
      interacted with each other, were identified to regulate further DEGs as target
      genes. Various genes, including FOS, UBB, MX1, STAT1, MAFB, and YWHAZ may be
      potential targets useful for the treatment of systemic vasculitis.

PMID- 28440410
TI  - A novel NOTCH3 mutation identified in patients with oral cancer by whole exome
      sequencing.
AB  - Oral cancer is a serious disease caused by environmental factors and/or
      susceptible genes. In the present study, in order to identify useful genetic
      biomarkers for cancer prediction and prevention, and for personalized treatment,
      we detected somatic mutations in 5 pairs of oral cancer tissues and blood samples
      using whole exome sequencing (WES). Finally, we confirmed a novel nonsense single
      nucleotide polymorphism (SNP; chr19:15288426A>C) in the NOTCH3 gene with sanger
      sequencing, which resulted in a N1438T mutation in the protein sequence. Using
      multiple in silico analyses, this variant was found to mildly damaging effects on
      the NOTCH3 gene, which was supported by the results from analyses using PANTHER,
      SNAP and SNPs&GO. However, further analysis using Mutation Taster revealed that
      this SNP had a probability of 0.9997 to be 'disease causing'. In addition, we
      performed 3D structure simulation analysis and the results suggested that this
      variant had little effect on the solubility and hydrophobicity of the protein and
      thus on its function; however, it decreased the stability of the protein by
      increasing the total energy following minimization (-1,051.39 kcal/mol for the
      mutant and -1,229.84 kcal/mol for the native) and decreasing one stabilizing
      residue of the protein. Less stability of the N1438T mutant was also supported by
      analysis using I-Mutant with a DDG value of -1.67. Overall, the present study
      identified and confirmed a novel mutation in the NOTCH3 gene, which may decrease
      the stability of NOTCH3, and may thus prove to be helpful in cancer prognosis.

PMID- 28440409
TI  - MicroRNA-145 regulates the differentiation of human adipose-derived stem cells to
      smooth muscle cells via targeting Kruppel-like factor 4.
AB  - Understanding the molecular mechanisms underlying human adipose-derived stem cell
      (hASC) differentiation to smooth muscle may contribute to the development of
      effective therapies for relevant muscle defects, such as bladder wall and
      urethral defects. A previous study described the differentiation of hASCs to
      smooth muscle cells (SMCs) by transforming growth factor-beta1 (TGF-beta1) and
      bone morphogenetic protein-4 (BMP4) treatment. The present study investigated
      whether microRNA-145 (miR-145) may be involved in the process of hASC
      differentiation. The expression of miR-145 was significantly increased during
      differentiation of ASCs to SMCs. SMC-specific genes and proteins, including a
      smooth muscle actin (alpha-SMA), smooth muscle protein-22alpha(SM22alpha),
      calponin and myosin heavy chain (SM-MHC) were upregulated by transfection of a
      miR-145 mimic. By contrast, these factors were downregulated following
      introduction of antisense oligonucleotides. In addition, Kruppel-like factor 4
      (KLF4) levels, which decreased during the differentiation of hASCs, were
      downregulated when the cells were transfected miR-145 mimics. Futhermore,
      inhibition of KLF4 by treatment with short-interfering-RNA against KLF4, resulted
      in increased expression of SMC-specific genes and proteins. In conclusion, the
      results of the present study demonstrated that by regulating KLF4, miR-145 may be
      involved in regulating smooth muscle differentiation of ASCs induced by TGF-beta1
      and BMP4.

PMID- 28440411
TI  - Effects of long-term post-ischemic treadmill exercise on gliosis in the aged
      gerbil hippocampus induced by transient cerebral ischemia.
AB  - Therapeutic exercise is an integral component of the rehabilitation of patients
      who have suffered a stroke. The objective of the present study was to use
      immunohistochemistry to investigate the effects of post-ischemic exercise on
      neuronal damage or death and gliosis in the aged gerbil hippocampus following
      transient cerebral ischemia. Aged gerbils (male; age, 22-24 months) underwent
      ischemia and were subjected to treadmill exercise for 1 or 4 weeks. Neuronal
      death was detected in the stratum pyramidale of the hippocampal CA1 region and in
      the polymorphic layer of the dentate gyrus using cresyl violet and Fluoro-Jade B
      histofluorescence staining. No significant difference in neuronal death was
      identified following 1 or 4 weeks of post-ischemic treadmill exercise. However,
      post-ischemic treadmill exercise affected gliosis (the activation of astrocytes
      and microglia). Glial fibrillary acidic protein-immunoreactive astrocytes and
      ionized calcium binding adaptor molecule 1-immunoreactive microglia were
      activated in the CA1 and polymorphic layer of the dentate gyrus of the group
      without treadmill exercise. Conversely, 4 weeks of treadmill exercise
      significantly alleviated ischemia-induced astrocyte and microglial activation;
      however, 1 week of treadmill exercise did not alleviate gliosis. These findings
      suggest that long-term post-ischemic treadmill exercise following transient
      cerebral ischemia does not influence neuronal protection; however, it may
      effectively alleviate transient cerebral ischemia-induced astrocyte and
      microglial activation in the aged hippocampus.

PMID- 28440412
TI  - A rare FANCA gene variation as a breast cancer susceptibility allele in an
      Iranian population.
AB  - Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by
      congenital abnormalities, progressive bone marrow failure and Fanconi anemia
      complementation group A (FANCA) is also a potential breast and ovarian cancer
      susceptibility gene. A novel allele with tandem duplication of 13 base pair
      sequence in promoter region was identified. To investigate whether the 13 base
      pair sequence of tandem duplication in promoter region of the FANCA gene is of
      high penetrance in patients with breast cancer and to determine if the presence
      of the duplicated allele was associated with an altered risk of breast cancer,
      the present study screened DNA in blood samples from 304 breast cancer patients
      and 295 normal individuals as controls. The duplication allele had a frequency of
      35.4 and 21.2% in patients with breast cancer and normal controls, respectively.
      There was a significant increase in the frequency of the duplication allele in
      patients with familial breast cancer compared with controls (45.1%, P=0.001).
      Furthermore, the estimated risk of breast cancer in individuals with a homozygote
      [odds ratio (OR), 4.093; 95% confidence intervals (CI), 1.957-8.561] or
      heterozygote duplicated genotype (OR, 3.315; 95% CI, 1.996-5.506) was higher
      compared with the corresponding normal homozygote genotype. In conclusion, the
      present study indicated that the higher the frequency of the duplicated allele,
      the higher the risk of breast cancer. To the best of our knowledge, the present
      study is the first to report FANCA gene duplication in patients with breast
      cancer.

PMID- 28440413
TI  - Different distributions of M1 and M2 macrophages in a mouse model of laser
      induced choroidal neovascularization.
AB  - Choroidal neovascularization (CNV) is a serious complication of age-related
      macular degeneration. The aim of the present study was to investigate the
      expression and distribution of M1 and M2 macrophages in a laser-induced CNV adult
      mouse model. The mRNA expression levels of M1, M2 and pan macrophage markers, and
      macrophage-associated angiogenic cytokines, were determined by reverse
      transcription-quantitative polymerase chain reaction. Immunofluorescence studies
      were performed to determine the location of the macrophages. The expression
      levels of M1 macrophage markers increased to a greater extent compared with M2
      markers in the retinal pigment epithelium (RPE)-choroid complexes following laser
      photocoagulation. By contrast, the expression levels of M2 macrophage markers
      increased primarily in the retinas. Immunofluorescence studies revealed that the
      increased number of cluster of differentiation (CD)206-positive cells were
      located primarily in the retina, whereas the CD80-positive cells were located
      around the site of CNVs in the RPE-choroid. In addition, the M1-associated
      cytokines increased to a greater extent in the RPE-choroid complexes, whereas the
      M2-associated cytokines were highly expressed in the retinas. These findings
      indicate that M1 and M2 macrophage numbers increased following CNV; however, the
      locations were different in this mouse model of laser-induced CNV. The results of
      the present study suggest that M1 macrophages have a more direct role in
      inhibiting the development of CNV.

PMID- 28440414
TI  - Thymosin beta4 promotes the survival and angiogenesis of transplanted endothelial
      progenitor cells in the infarcted myocardium.
AB  - The survival of transplanted stem cells in ischemic tissue is poor. In the
      present study, the effects of thymosin beta4 (Tbeta4) on the survival and
      angiogenesis of endothelial progenitor cells (EPCs) and improvement in cardiac
      functions after transplantation of Tbeta4-treated EPCs in the infarcted
      myocardium were investigated. EPCs were isolated from bone marrow of adult male
      rats and incubated in Endothelial Basal Medium-2. Then the cells were treated
      with Tbeta4 at different concentrations (0.05, 0.1 and 0.2 uM), and cells
      incubated with DMEM were set as controls. MTT assay, Transwell assay and tube
      formation in Matrigel were used to detect cell viability, migration and
      angiogenesis, respectively. For examining the protective effect of Tbeta4 on
      EPCs, the cells were also incubated in the condition of hypoxia and serum
      deprivation. p-Akt expression was also examined using western blot analysis. Rat
      models of myocardial infarction (MI) were established by ligation of the anterior
      descending branch of the left coronary artery. At four weeks after
      intramyocardial injection of Tbeta4-treated EPCs, the changes in cardiac
      functions, size of the scar tissue and density of microvessels were examined by
      echocardiography, Masson's trichrome staining, immunohistochemistry and
      fluorescence in situ hybridization (FISH) for the Y-chromosome. Tbeta4 enhanced
      EPC viability, protected the cells from apoptosis in hypoxia and serum
      deprivation, and promoted the proliferation and migration of the cells and
      formation of capillary-like structures in the cells. Moreover, Tbeta4 increased p
      Akt expression in the cells. The cytoprotective and proangiogenic effects of
      Tbeta4 were in a dose-dependent manner. Tbeta4-treated EPCs improved cardiac
      function, enhanced the repair of the infarcted myocardium, and promoted
      angiogenesis after transplantation in the infarcted myocardium. In conclusion,
      pretreatment of EPCs with Tbeta4 is a novel strategy for the repair of ischemic
      tissue after transplantation in MI.

PMID- 28440415
TI  - UDP and NTF2 are the most consistently expressed genes in Panax ginseng roots at
      different growth stages.
AB  - Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis
      relies on normalization against a consistently expressed reference gene. However,
      it has been reported that reference gene expression levels often vary markedly
      between samples as they are usually selected based solely on convention. The
      advent of RNA sequencing technology offers the opportunity to select reference
      genes with the least variability in steady-state transcript levels. To identify
      the most consistently stable genes, which are a prerequisite for obtaining
      reliable gene expression data, the present study analyzed transcriptomes from six
      Panax ginseng transcriptome data sets, representing six growth stages, and
      selected 21 candidate reference genes for screening using RT-qPCR. Of the 21
      candidate genes, 13 had not been reported previously. The geNorm, NormFinder and
      BestKeeper programs were used to analyze the stability of the 21 candidate
      reference genes. The results showed that UDP-N-acetylgalactosamine transporter
      and nuclear transport factor 2 were likely to be the optimal combination of
      reference genes for use in investigations of ginseng. The novel reference genes
      were validated by correlating the gene expression profiles of four pathogenesis
      related protein genes generated from RT-qPCR, with their expression levels
      calculated from the RNA sequencing data. The expression levels were well
      correlated, which demonstrated their value in performing RT-qPCR analyses in
      ginseng.

PMID- 28440416
TI  - FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid
      cancers depending on p53 status.
AB  - Fucose residues of cell surface glycans, which play important roles in growth,
      invasion and metastasis, are added by fucosyltransferases (FUTs) and removed by
      alpha-L-fucosidases (FUCAs). By the differential display method, we isolated a 3'
      non-coding region of alpha-L-fucosidase-1 (FUCA1) (a gene coding for the
      lysosomal fucosidase-1 enzyme) as a wild-type p53-inducible gene: 18S and 20S
      FUCA1 mRNA species were induced in Saos-2 cells transfected with a temperature
      sensitive p53 mutant at the permissive temperature. By microarray analyses of
      thyroid cancer biopsy samples, FUCA1 RNA expression levels were found to be lower
      in anaplastic thyroid cancer samples (ATCs), while they were higher in papillary
      thyroid cancer samples (PTCs) and in normal thyroid tissues. Since most ATCs were
      reported to carry the mutated form of p53, while PTCs carry mostly the wild-type
      form of p53, it is likely that FUCA1 expression levels are regulated, at least in
      part, by the p53 status in thyroid cancers. In order to better understand the
      role played by FUCA genes in thyroid tumorigenesis, we examined the clonogenic
      potential in vitro of thyroid cell lines transfected with either FUCA1 or FUCA2
      (the latter gene coding for a secreted, non-lysosomal enzyme). We found that
      alpha-L-fucosidases did not suppress grossly cell growth. Contrary to what we
      observed with the expression of FUCA1, the FUT8 expression levels were found high
      in ATCs but lower in PTCs and normal thyroid tissues. Taken together, these
      results suggest the possibility that the higher fucose levels on cell surface
      glycans of aggressive ATCs, compared to those of less aggressive PTCs, may be at
      least in part responsible for the more aggressive and metastatic phenotype of
      ATCs compared to PTCs, as the expression levels of FUCA1 and FUT8 were inversely
      related in these two types of cancers.

PMID- 28440417
TI  - Increased CD19+CD24+CD27+ B regulatory cells are associated with insulin
      resistance in patients with type I Hashimoto's thyroiditis.
AB  - Hashimoto's thyroiditis (HT) is characterized by dysregulated immune responses
      and is commonly associated with insulin resistance. However, the mechanism of
      insulin resistance in HT remains to be fully elucidated. The aim of the present
      study was to investigate the correlation between the percentage of B regulatory
      lymphocytes (Bregs) and insulin resistance in patients with HT but with normal
      thyroid function (type I). A total of 59 patients with type I HT and 38 healthy
      volunteers were enrolled in the study. An oral glucose tolerance test was
      performed to measure insulin secretion and assess beta-cell functions. Flow
      cytometry was performed to examine the percentages of lymphocyte populations. The
      patients with HT exhibited normal fasting and postprandial glucose and fasting
      insulin secretion, but increased secretion of early-phase and total insulin. The
      patients with HT also had insufficient beta-cell compensation for insulin
      resistance, indicated by a reduced disposition index, in the fasting state. An
      elevation in the percentage of CD19+CD24+CD27+ Bregs was also observed, which
      correlated positively with insulin secretion and insulin resistance in the
      fasting state. The patients with type I HT had postprandial insulin resistance
      and insufficient beta-cell compensation for fasting insulin resistance.
      Therefore, the increase in CD19+CD24+CD27+ Bregs was closely associated with
      fasting insulin secretion. These results provide novel insight into the mechanism
      of insulin resistance in HT.

PMID- 28440418
TI  - Two novel mutations in ERCC6 cause Cockayne syndrome B in a Chinese family.
AB  - Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized
      principally by progressive growth failure, neurologic abnormality and premature
      aging. Mutations of excision repair cross-complementation group 6 (ERCC6) and
      ERCC8 are predominantly responsible for CS, of which mutation of ERCC6 accounts
      for approximately two thirds of cases. The current report describes two siblings
      with severe neurologic abnormality and premature aging. Whole exome sequencing
      identified two novel mutations in ERCC6 that had not been previously reported.
      One was a nonsense mutation at codon 612 in exon 9 (c.1834C>T, p.Arg612Ter), and
      the other a missense mutation at codon 975 in exon 16 (c.2923C>T, p.Arg975Trp).
      Cosegregation analysis revealed c.1834C>T was paternal and c.2923C>T was
      maternal. A healthy baby with no mutated alleles was delivered based on prenatal
      diagnosis performed by genetic testing of amniocytes for the causative mutation.
      The present study will enrich the clinical and genetic spectrum of CS in China
      and world wide, and provides more evidence for future genotype-phenotype studies.

PMID- 28440419
TI  - Different effects of (+)-borneol and (-)-borneol on the pharmacokinetics of
      osthole in rats following oral administration.
AB  - Osthole is the primary active component of a number of herbal plants such as the
      Cnidium monnieri fruit. In traditional Chinese herb medicine, osthole is commonly
      used in combination with borneol to obtain improved pharmacological effects. The
      aim of the present study was to investigate the effect of borneol enantiomers on
      the pharmacokinetics of osthole. An appropriate high-performance liquid
      chromatography (HPLC) method was applied to determine the concentrations of
      osthole in plasma. Following oral administration of osthole alone or combined
      with borneol in rats, blood samples were collected and analyzed by HPLC. The
      results demonstrated that there were statistically significant differences in the
      pharmacokinetic parameters of osthole between osthole administration alone and co
      administration with borneol. When combined with synthetic borneol, the AUC0-t,
      AUC0-infinity and Cmax of osthole increased by 48.153, 104.708 and 92.630%,
      respectively, while the CL/F decreased by 51.251%. When combined with (+)
      borneol, the AUC0-t, AUC0-infinity and Cmax of osthole were increased by 61.561,
      78.167, and 51.769%, respectively, while the CL/F decreased by 44.174% (P<0.01).
      In addition, when combined with (-)-borneol, the AUC0-t, AUC0-infinity and Cmax
      of osthole increased by 115.856, 167.786 and 271.289%, respectively, while the
      CL/F decreased by 60.686% (P<0.01). These results indicated that borneol may
      enhance gastrointestinal absorption and inhibit the metabolism of osthole. In
      addition, the promotional effect of (-)-borneol on the pharmacokinetic parameters
      of osthole was greater than that of (+)-borneol.

PMID- 28440420
TI  - Wound healing effect of an Astragalus membranaceus polysaccharide and its
      mechanism.
AB  - In the present study, a novel polysaccharide, APS2-1, was isolated and purified
      from Astragalus membranaceus using DEAE-cellulose and Sephadex G-100
      chromatography. The effect of APS2-1 on the promotion of wound healing was
      evaluated and its preliminary mechanism was investigated. In vitro experiments
      showed that APS2-1 was able to promote human skin fibroblast (HSF) propagation
      and accelerate cell cycle progression. For further examination, a scalded mice
      model was used to verify the effect of APS2-1 and investigate its mechanism of
      action. The analysis of biochemical parameters, including cyclin D1, inhibitor of
      nuclear factor kappaBalpha (IkappaBalpha), transforming growth factor (TGF)
      beta1, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF)
      showed that APS2-1 inhibited the increase in cyclin D1 and IkappaBalpha, and
      promoted the expression of TGF-beta1, bFGF and EGF, which was further confirmed
      by histopathological observation. These results suggested that APS2-1 possessed
      high potential in wound healing and its mechanism was associated with inhibiting
      inflammation, accelerating cell cycle and promoting the secretion of repair
      factors.

PMID- 28440421
TI  - Allicin induces the upregulation of ABCA1 expression via PPARgamma/LXRalpha
      signaling in THP-1 macrophage-derived foam cells.
AB  - Allicin is considered anti-atherosclerotic due to its antioxidant and anti
      inflammatory effects, which makes it an important drug for the prevention and
      treatment of atherosclerosis. However, the effects of allicin on foam cells are
      unclear. Thus, in this study, we examined the effects of allicin on lipid
      accumulation via peroxisome proliferator-activated receptor gamma
      (PPARgamma)/liver X receptor alpha (LXRalpha) in THP-1 macrophage-derived foam
      cells. THP-1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24
      h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam
      cell formation. The results of Oil Red O staining and high-performance liquid
      chromatography (HPLC) revealed showed that pre-treatment of the foam cells with
      allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester
      levels in cells, and also decreased lipid accumulation. Moreover, allicin
      upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted
      cholesterol efflux. However, these effects were significantly abolished by
      transfection with siRNA targeting ABCA1. Furthermore, PPARgamma/LXRalpha
      signaling was activated by allicin treatment. The allicin-induced upregulation of
      ABCA1 expression was also abolished by PPARgamma inhibitor (GW9662) and siRNA or
      LXRalpha siRNA co-treatment. Overall, our data demonstrate that the allicin
      induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid
      accumulation via PPARgamma/LXRalpha signaling in THP-1 macrophage-derived foam
      cells.

PMID- 28440422
TI  - Variable TERRA abundance and stability in cervical cancer cells.
AB  - Telomeres are transcribed into long non-coding RNA, referred to as telomeric
      repeat-containing RNA (TERRA), which plays important roles in maintaining
      telomere integrity and heterochromatin formation. TERRA has been well
      characterized in HeLa cells, a type of cervical cancer cell. However, TERRA
      abundance and stability have not been examined in other cervical cancer cells, at
      least to the best of our knowledge. Thus, in this study, we measured TERRA levels
      and stability, as well as telomere length in 6 cervical cancer cell lines, HeLa,
      SiHa, CaSki, HeLa S3, C-33A and SNU-17. We also examined the association between
      the TERRA level and its stability and telomere length. We found that the TERRA
      level was several fold greater in the SiHa, CaSki, HeLa S3, C-33A and SNU-17
      cells, than in the HeLa cells. An RNA stability assay of actinomycin D-treated
      cells revealed that TERRA had a short half-life of ~4 h in HeLa cells, which was
      consistent with previous studies, but was more stable with a longer half-life (>8
      h) in the other 5 cell lines. Telomere length varied from 4 to 9 kb in the cells
      and did not correlate significantly with the TERRA level. On the whole, our data
      indicate that TERRA abundance and stability vary between different types of
      cervical cancer cells. TERRA degrades rapidly in HeLa cells, but is maintained
      stably in other cervical cancer cells that accumulate higher levels of TERRA.
      TERRA abundance is associated with the stability of RNA in cervical cancer cells,
      but is unlikely associated with telomere length.

PMID- 28440423
TI  - Upregulated microRNA-429 inhibits the migration of HCC cells by targeting TRAF6
      through the NF-kappaB pathway.
AB  - Increasing evidence indicates that miR-429 is involved in tumor suppression in
      various human cancers. however, its role in hepatocellular carcinoma (HCC)
      remains unclear. In the present study, we found that miR-429 was significantly
      downregulated in HCC tissue samples and cell lines. Upregulation of miR-429
      markedly suppressed proliferation and migration of HCC cells. Moreover, we
      identified TRAF6 as a direct target of miR-429. Downregulation of TRAF6 partially
      attenuated the oncogenic effect of anti-miR-429 on HCC cells. Ectopic expression
      of miR-429 in HCC cells inhibited TCF-4 activity as well as nuclear accumulation
      of P65 and expression of the NF-kappaB targets c-Myc and phosphorylation of TAK1.
      In a nude xenograft model, miR-429 upregulation significantly decreased HCC
      growth. In conclusion, by targeting TRAF6, miR-429 is downregulated in HCC and
      inhibits HCC cell proliferation and motility. Our data suggest that miR-429 may
      serve as a potential anticancer target for the treatment of HCC.

PMID- 28440424
TI  - Therapeutic potential of the antidiabetic drug metformin in small bowel
      adenocarcinoma.
AB  - Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract
      tumors and approximately 0.5% of all cancer cases. Recent studies have indicated
      that the use of metformin, one of the most commonly prescribed antidiabetic
      drugs, is associated with a better prognosis for certain malignant diseases.
      However, there have been no reports on the effect of metformin in SBAC. In the
      present study, we evaluated the effect of metformin on human SBAC cell
      proliferation in vitro and in vivo and identified the microRNAs (miRNAs)
      associated with its antitumor effects. Metformin inhibited the proliferation of
      HuTu80 cells in a time- and dose-dependent manner. Importantly, metformin reduced
      the expression of cyclin D1, cyclin E, cyclin-dependent kinase 4, and
      phosphorylated retinoblastoma protein, which resulted in cell cycle arrest at the
      G0/G1 phase. This arrest was accompanied by activation of AMPKalpha and
      inhibition of mammalian target of rapamycin and p70s6k. Additionally, metformin
      reduced the levels of phosphorylated epidermal growth factor receptor and ROR2 as
      well as markedly altered miRNA expression in HuTu80 cells. Metformin also
      inhibited tumor growth in vivo in a xenograft mouse model. Our data suggest that
      metformin might have therapeutic potential in SBAC.

PMID- 28440425
TI  - Mitochondrial transcription factor A (TFAM) is upregulated in glioma.
AB  - Mitochondrial transcription factor A (TFAM), which was initially discovered as a
      transcription factor for mitochondrial DNA, has known to be critical for the
      regulation of mitochondrial DNA. However the possible involvement of TFAM in
      cancer is largely unknown. In this study, we have provided some evidence that
      TFAM may have a potential role in brain tumor. Western blot analysis with anti
      TFAM antibody indicated that TFAM is overexpressed in glioblastoma cell lines
      including U87MG and U251MG. Transcriptome profiling of U87MG and U251MG cells by
      using deep-sequencing revealed that TFAM transcripts were upregulated in these
      cells compared to its of cerebral cortex. Confocal microscopic analysis of U251MG
      cells with anti-TFAM antibody showed that TFAM is located to the dot-like
      structure close to nucleus, probably mitochondria and endosome.
      Immunohistochemical analysis of glioma tissue specimens indicated that TFAM is
      highly upregulated. Bioinformatical analysis with Rembrandt knowledgebase also
      supported that TFAM mRNA is upregulated in glioma patients. Taken together, the
      results presented in this study obviously provided the evidence that TFAM was
      upregulated in glioma cell line and glioma tissue specimens. Therefore TFAM may
      be a novel diagnostic marker and therapeutic target for glioma and other cancer.

PMID- 28440426
TI  - Downregulation of microRNA-30d promotes cell proliferation and invasion by
      targeting LRH-1 in colorectal carcinoma.
AB  - The aberrant expression of miR-30d has been reported in several types of human
      malignancies. However, its biological function in colorectal cancer (CRC) remains
      largely unknown. In this study, we identified that miR-30d was significantly
      downregulated in CRC tissues compared to that observed in normal controls as
      detected by RT-qPCR analysis. Downregulation of miR-30d was significantly
      associated with aggressive clinicopathological parameters including tumor
      differentiation, invasive depth, TNM stage, lymph node metastasis, distant
      metastasis, and poor prognosis. Furthermore, functional analysis revealed that
      overexpression of miR-30d significantly inhibited cell proliferation, caused cell
      cycle arrest at the G0/G1 phase, suppressed cell migration and invasion, induced
      cell apoptosis in vitro, and decreased tumor growth in a xenograft mouse model.
      Bioinformatic analysis and dual-luciferase reporter assay revealed that liver
      receptor homologue-1 (LRH-1) is a direct target of miR-30d in CRC cells. Rescue
      assay showed that LRH-1 overexpression could restore the inhibitory effect of miR
      30d on CRC cells. In addition, miR-30d overexpression suppressed the activation
      of key components of the Wnt/beta-catenin signaling pathway, beta-catenin, c-Myc
      and cyclin D1, which contributed to the inhibition of CRC development. Thus, our
      findings suggest that miR-30d functions as a tumor suppressor against CRC
      development and miR-30d/LRH-1/Wnt signaling may be novel potential targets for
      CRC treatment.

PMID- 28440427
TI  - Downregulation of miR-200c protects cardiomyocytes from hypoxia-induced apoptosis
      by targeting GATA-4.
AB  - Hypoxia-induced cardiomyocyte apoptosis plays an important role in the
      development of ischemic heart disease. MicroRNAs (miRNAs or miRs) are emerging as
      critical regulators of hypoxia-induced cardiomyocyte apoptosis. miR-200c is an
      miRNA that has been reported to be related to apoptosis in various pathological
      processes; however, its role in hypoxia-induced cardiomyocyte apoptosis remains
      unclear. In the present study, we aimed to investigate the potential role and
      underlying mechanism of miR-200c in regulating hypoxia-induced cardiomyocyte
      apoptosis. We found that miR-200c was significantly upregulated by hypoxia in
      cardiomyocytes, as detected by reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR). The lactate dehydrogenase, MTT, Annexin V/propidium
      iodide apoptosis and caspase-3 activity assays showed that downregulation of miR
      200c markedly improved cell survival and suppressed the apoptosis of
      cardiomyocytes in response to hypoxia. Bioinformatics analysis and the dual
      luciferase reporter assay demonstrated that miR-200c directly targeted the 3'
      untranslated region of GATA-4, an important transcription factor for
      cardiomyocyte survival. RT-qPCR and western blot analysis showed that suppression
      of miR-200c significantly increased GATA-4 expression. Furthermore,
      downregulation of miR-200c upregulated the expression of the anti-apoptotic gene
      Bcl-2. However, the protective effects against hypoxia induced by the
      downregulation of miR-200c were significantly abolished by GATA-4 knockdown.
      Taken together, our results suggest that downregulation of miR-200c protects
      cardiomyocytes from hypoxia-induced apoptosis by targeting GATA-4, providing a
      potential therapeutic molecular target for the treatment of ischemic heart
      disease.

PMID- 28440428
TI  - Inhibition of ATR potentiates the cytotoxic effect of gemcitabine on pancreatic
      cancer cells through enhancement of DNA damage and abrogation of ribonucleotide
      reductase induction by gemcitabine.
AB  - Pancreatic cancer is a highly malignant disease with a dismal prognosis.
      Gemcitabine (GEM)-based chemotherapy is the first-line treatment for patients
      with advanced disease, although its efficacy is very limited, mainly due to drug
      resistance. Ataxia telangiectasia and Rad3-related (ATR) plays a critical role in
      the DNA damage response (DDR) which has been implicated in GEM resistance. Thus,
      targeting ATR represents a promising approach to enhance GEM antitumor activity.
      In the present study, we tested the antitumor activity of AZ20, a novel ATR
      selective inhibitor, alone or combined with GEM in 5 pancreatic cancer cell
      lines. AZ20 treatment of the pancreatic cancer cell lines resulted in growth
      inhibition, with IC50 values ranging from 0.84 to 2.4 uM, but limited cell death.
      As expected, treatment of pancreatic cancer cell lines with AZ20 caused decreased
      phosphorylation of CHK1 (S-345). However, this was accompanied by DNA damage and
      S and G2/M cell cycle arrest, independent of TP53 gene mutational status.
      Importantly, combination of AZ20 with GEM resulted in synergistic inhibition of
      cell growth and cooperative induction of cell death in the pancreatic cancer cell
      lines. AZ20 significantly increased GEM-induced DNA damage and almost completely
      abrogated GEM-induced expression of the M2 subunit of ribonucleotide reductase.
      These findings suggest that inhibition of ATR is a promising strategy to enhance
      the antitumor activity of GEM for treating pancreatic cancer.

PMID- 28440429
TI  - Cathepsin B expression in colorectal cancer in a Middle East population:
      Potential value as a tumor biomarker for late disease stages.
AB  - Cathepsin B (CTSB), is a cysteine protease belonging to the cathepsin (Clan CA)
      family. The diagnostic and prognostic significance of increased CTSB in the serum
      of cancer patients have been evaluated for some tumor types. CTSB serum and
      protein levels have also been reported previously in colorectal cancer (CRC) with
      contradictory results. The aim of the present study was to investigate CTSB
      expression in CRC patients and the association of CTSB expression with various
      tumor stages in a Middle East population. Serum CTSB levels were evaluated in 70
      patients and 20 healthy control subjects using enzyme-linked immunosorbant assay
      (ELISA) technique. CTSB expression was determined in 100 pairs of CRC tumor and
      adjacent normal colonic tissue using quantitative PCR for mRNA levels. Detection
      of CTSB protein expression in tissues was carried out using both
      immunohistochemistry and western blotting techniques. ELISA analysis showed that
      in sera obtained from CRC patients, the CTSB concentration was significantly
      higher in late stage patients with lymph node metastases when compared to early
      stage patients with values of 2.9 and 0.33 ng/ml, respectively (P=0.001). The
      majority of tumors studied had detectable CTSB protein expression with
      significant increased positive staining in tumors cells when compared with
      matched normal colon subjects (P=0.006). The mRNA expression in early stage CRC
      compared to late stage CRC was 0.04+/-0.01 and 0.07+/-0.02, respectively.
      Increased mRNA expression was more frequently observed in the advanced cancer
      stages with lymph node metastases when compared with the control (P=0.002). Mann
      Whitney test and paired t-test were used to compare serum CTSB and mRNA levels in
      early and late tumor stage. A subset of four paired tissue extracts were analyzed
      by western blotting. The result confirmed a consistent increase in the CTSB
      protein expression level in tumor tissues compared with that noted in the
      adjacent normal mucosal cells. These findings indicate that CTSB may be an
      important prognostic biomarker for late stage CRC and cases with lymph node
      metastases in the Middle Eastern population. Monitoring serum CTSB in CRC
      patients may predict and/or diagnose cases with lymph node metastases.

PMID- 28440430
TI  - Perfluorooctanoic acid induces oxidative damage and mitochondrial dysfunction in
      pancreatic beta-cells.
AB  - Several environmental contaminants have been linked to the development of
      diabetes and increased diabetes-associated mortality. Perfluorooctanoic acid
      (PFOA) is a widely used perfluoroalkane found in surfactants and lubricants, and
      in processing aids used in the production of polymers. Furthermore, PFOA has been
      detected in humans, wildlife and the environment. The present study investigated
      the toxic effects of PFOA on rat pancreatic beta-cell-derived RIN-m5F cells. Cell
      viability, apoptosis, reactive oxygen and nitrogen species, cytokine release and
      mitochondrial parameters, including membrane potential collapse, reduced
      adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release
      were assessed. PFOA significantly decreased RIN-m5F cell viability and increased
      apoptosis. Exposure to PFOA increased the formation of reactive oxygen species,
      mitochondrial superoxide, nitric oxide and proinflammatory cytokines.
      Furthermore, PFOA induced mitochondrial membrane potential collapse and reduced
      adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release.
      These results indicate that PFOA is associated with the induction of apoptosis in
      RIN-m5F cells, and induces cytotoxicity via increased oxidative stress and
      mitochondrial dysfunction.

PMID- 28440431
TI  - GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral
      blood lymphocytes following exposure to ionizing radiation.
AB  - The identification of rapid, sensitive and high-throughput biomarkers is
      imperative in order to identify individuals harmed by radiation accidents, and
      accurately evaluate the absorbed doses of radiation. DNA microarrays have
      previously been used to evaluate the alterations in growth/differentiation factor
      15 (GDF15) gene expression in AHH-1 human lymphoblastoid cells, following
      exposure to gamma-rays. The present study aimed to characterize the relationship
      between the dose of ionizing radiation and the produced effects in GDF-15 gene
      expression in AHH-1 cells and human peripheral blood lymphocytes (HPBLs). GDF-15
      mRNA and protein expression levels following exposure to gamma-rays and neutron
      radiation were assessed by reverse transcription-quantitative polymerase chain
      reaction and western blot analysis in AHH-1 cells. In addition, alterations in
      GDF-15 gene expression in HPBLs following ex vivo irradiation were evaluated. The
      present results demonstrated that GDF-15 mRNA and protein expression levels in
      AHH-1 cells were significantly upregulated following exposure to gamma-ray doses
      ranging between 1 and 10 Gy, regardless of the dose rate. A total of 48 h
      following exposure to neutron radiation, a dose-response relationship was
      identified in AHH-1 cells at gamma-ray doses between 0.4 and 1.6 Gy. GDF-15 mRNA
      levels in HPBLs were significantly upregulated following exposure to gamma-ray
      doses between 1 and 8 Gy, within 4-48 h following irradiation. These results
      suggested that significant time- and dose-dependent alterations in GDF-15 mRNA
      and protein expression occur in AHH-1 cells and HPBLs in the early phases
      following exposure to ionizing radiation. In conclusion, alterations in GDF-15
      gene expression may have potential as a biomarker to evaluate radiation exposure.

PMID- 28440432
TI  - RON and c-Met facilitate metastasis through the ERK signaling pathway in prostate
      cancer cells.
AB  - Prostate cancer (PCa) is a metastatic malignant cancer driven by complex
      pathological mechanisms and characterized by poor long-term prognosis. Metastasis
      is the main cause of death of PCa patients, yet the molecular mechanisms of this
      process are poorly understood. In the present study, positive co-expression of
      RON and c-Met was observed in human clinical PCa tissues (biopsy material), as
      detected by immunohistochemical staining and quantitative real-time PCR. We
      investigated this further in PCa cells, demonstrating that the inhibition of RON
      and c-Met with foretinib (GSK1363089) suppressed metastasis and promoted the
      reversal of the epithelial-to-mesenchymal transition (EMT) in PCa cells.
      Furthermore, the invasion and migration of PCa cells were enhanced by the
      exogenous activation of RON with MSP and c-Met with HGF, whereas silencing of RON
      and c-Met attenuated the invasion and metastasis of the PCa cells. Our data also
      demonstrated that HGF/c-Met, but not the MSP-RON signaling pathway may be the
      dominant mechanism for PCa EMT. We further revealed that RON and c-Met facilitate
      metastasis via ERK1/2 signaling. These findings indicate that RON and c-Met
      facilitate metastasis through ERK1/2 signaling and that targeting RON and c-Met
      with foretinib may be an attractive therapeutic option for suppressing PCa
      metastasis.

PMID- 28440433
TI  - Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in
      vitro and in vivo.
AB  - As a natural compound, Ornithogalum caudatum Ait is primarily used as an anti
      inflammatory and antitumor agent in Chinese folk medicine. In 1992, OSW-1 was
      isolated from this compound, which is a new member of cholestane saponin family.
      In numerous recent studies, OSW-1 has been shown to have powerful cytotoxic
      anticancer effects against various malignant cells. However, the therapeutic
      efficacy of OSW-1 on colon cancer and the underlying mechanism are not
      understood. To explore the mechanism underlying OSW-1 in antitumor therapy, a
      therapeutic function analysis of OSW-1 on colon cancer was performed in vitro and
      in vivo. It was shown that with low toxicity on normal colonic cells, OSW-1
      suppresses colon cancer cells in vitro and this inhibition was via the intrinsic
      apoptotic pathway, which increased cellular calcium, changed mitochondrial
      membrane potential, disrupted mitochondrial morphology, and led to the release of
      cytochrome c and the activation of caspase-3. Furthermore, in a nude mouse model,
      OSW-1 had a powerful effect on suppressing colon tumor proliferation without
      significant side effects through the apoptosis pathway. Taken together, these
      results demonstrate that OSW-1 is a potential drug for colon cancer treatment.

PMID- 28440434
TI  - Preclinical studies for the combination of paclitaxel and curcumin in cancer
      therapy (Review).
AB  - Cancer is one of the most common causes of death and remains the first in China
      and the second in the US. The common treatments for cancer include surgery,
      radiation, chemotherapy, targeted therapy and immunotherapy, while chemotherapy
      remains one of the most important treatments. However, the efficacy of
      chemotherapy is limited due to drug induced-toxicities and resistance,
      particularly multiple drug resistance (MDR). Therefore, discovery and development
      of novel therapeutic drugs and/or combination therapy are urgently needed to
      reduce toxicity and improve efficacy. Paclitaxel has been widely used to treat
      various cancers including cervical, breast, ovarian, brain, bladder, prostate,
      liver and lung cancers. However, its therapeutic efficacy is limited and MDR is a
      major obstacle. Recently, numerous preclinical studies have shown that the
      combination of paclitaxel and curcumin may be an ideal strategy to reverse MDR
      and synergistically improve their therapeutic efficacy in cancer therapy. This
      review mainly focuses on the current development and progress of the combination
      of paclitaxel and curcumin in cancer therapy preclinically.

PMID- 28440435
TI  - Mitochondria targeting and near-infrared fluorescence imaging of a novel
      heptamethine cyanine anticancer agent.
AB  - The future of personalized cancer treatments relies on the development of
      functional agents that have tumor-targeted anticancer activities and can be
      detected in tumors using imaging. However, application of these functional agents
      in the clinic has been limited due to inefficient drug delivery, low specificity
      for tumor imaging, development of drug resistance, low signal-to-noise ratio and
      safety concerns regarding potential toxicity. Currently, the most common strategy
      to develop these functional agents is to conjugate therapeutic agents with the
      appropriate fluorescent probe. The present study synthesized a novel mitochondria
      targeted heptamethine cyanine (Cy) derivative Cy-triphenylphosphonium. The newly
      developed compound exhibited stronger near infrared (NIR) fluorescence and
      reacted with bovine serum albumin. In addition, it preferentially accumulated in
      the mitochondria of cancer cells, as observed using confocal microscopy, and
      efficiently reduced cancer cell viability (IC50=3.04 uM). This novel
      multifunctional heptamethine Cy derivative, with cancer mitochondria targeting
      and NIR fluorescence imaging, may be promising as an alternative anticancer
      agent.

PMID- 28440436
TI  - Annexin A2 inhibition suppresses ovarian cancer progression via regulating beta
      catenin/EMT.
AB  - Annexin A2 is a member of the Annexin family that acts as a Ca2+-dependent
      phospholipid and membrane binding protein, which is associated with the survival
      and spread of multiple neoplasms. However, the function of Annexin A2 in ovarian
      cancer progression remains unclear. In this study, we aimed to investigate the
      role and underlying molecular mechanism of Annexin A2 in cell proliferation and
      invasion in ovarian cancer. We found that the mRNA expression of Annexin A2 was
      upregulated in ovarian cancer tissues and cell lines. In the loss-of-function of
      Annexin A2, beta-catenin was indicated to be significantly suppressed and EMT
      constrained. Moreover, cell proliferation and invasion were both markedly
      inhibited by the downregulation of Annexin A2. Additionally, the overexpression
      of beta-catenin obviously reversed the effect of Annexin A2 on EMT, and cell
      proliferation and invasion, indicating that Annexin A2 suppression regulated EMT
      through controlling beta-catenin. Taken together, this study showed that Annexin
      A2 inhibition suppresses proliferation and invasion in ovarian cancer via beta
      catenin/EMT, proposing the potential role of Annexin A2 in the prevention and
      treatment of ovarian cancer.

PMID- 28440437
TI  - Autophagy-related protein 12 associates with anti-apoptotic B cell lymphoma-2 to
      promote apoptosis in gentamicin-induced inner ear hair cell loss.
AB  - The aim of the present study was to investigate the underlying mechanisms of
      autophagy in a gentamicin (GM)-induced ototoxic model, and to establish whether
      the blocking of autophagy significantly increases the survival of inner ear hair
      cells. Cochleae were carefully dissected from four day-old C57BL/6J mice and
      randomly divided into three groups prior to explant culture: Control (culture
      medium), GM-treated (culture medium + GM) and GM + 3-methyladenine (3-MA; culture
      medium + GM + 3-MA). Transmission electron microscopy, immunofluorescence and
      western blotting were performed to observe the expression of the autophagy
      protein microtubule-associated protein 1A/B-light chain 3 in explant cultures
      treated with GM and the autophagy inhibitor 3-MA. Administration of GM in in
      vitro mouse cochlear culture induced apoptosis and the formation of autophagic
      vesicles and autophagosomes in hair cells. Notably, combined treatment with GM
      and 3-MA to block autophagy significantly increased the survival of inner ear
      hair cells. Furthermore, it was indicated that the simultaneous expression and
      interaction of Atg12 with Bcl-2 following GM treatment co-integrated autophagy
      with apoptosis in the cochlea. The results of the present study demonstrated that
      autophagy was involved in GM-induced ototoxicity. Additionally, Atg12 may serve a
      protective role by binding to Bcl-2. Therefore, Atg12 may be a potential
      therapeutic target for the treatment of GM-induced cochlear hair loss.

PMID- 28440438
TI  - Loss of heterozygosity in FANCG, FANCF and BRIP1 from head and neck squamous cell
      carcinoma of the oral cavity.
AB  - Recent advances have been made in the understanding of Fanconi anemia (FA), a
      hereditary disease that increases the risk for head and neck squamous cell
      carcinomas (HNSCC) by 500- to 700-fold. FA patients harbour germline mutations in
      genes of cellular DNA repair pathways that are assumed to facilitate the
      accumulation of mutations during HNSCC development. Mutations in these FA genes
      may also contribute to HNSCC in general. In the present study, we analysed three
      FA genes; FANCF, FANCG and BRIP1, that are involved in the repair of DNA inter
      strand cross-links, in HNSCC and their potential role for patient survival. We
      measured loss of heterozygosity (LOH) mutations at eight microsatellite loci
      flanking three FA genes in 54 HNSCC of the oral cavity and corresponding blood
      samples. Survival analyses were carried out using mutational data and clinical
      variables. LOH was present in 17% (FANCF region), 41% (FANCG region) and 11%
      (BRIP1 region) of the patients. Kaplan-Meier survival curves and log-rank tests
      indicated strong clinical predictors (lymph node stages with decreased survival:
      p=2.69e-12; surgery with improved survival: p=0.0005). LOH in the FANCF region
      showed a weaker association with decreased overall survival (p=0.006), which
      however, did not hold in multivariate analyses. LOH may predominantly indicate
      copy number gains in FANCF and losses in FANCG and BRIP1. Integration of copy
      number data and gene expression proved difficult as the available sample sets did
      not overlap. In conclusion, LOH in FA genes appears to be a common feature of
      HNSCC development seen here in 57% of patients and other mutation types may
      increase this mutation frequency. We suggest larger patient cohorts would be
      needed to test the observed association of LOH in FANCF and patient survival
      comprehensively.

PMID- 28440439
TI  - MicroRNA-26a inhibits proliferation and metastasis of human hepatocellular
      carcinoma by regulating DNMT3B-MEG3 axis.
AB  - miR-26a is known to play an important oncosuppressive role in HCC. However, its
      regulatory role and relationship with other non-coding RNAs is less clear. In the
      present study, we report that the expression levels of miR-26a and long non
      coding RNA (lncRNA) maternally expressed gene 3 (MEG3) were frequently
      downregulated in HCC tissues compared to matched non-malignant tissues. In
      addition, the expression levels of miR-26a and MEG3 were negatively correlated
      with the tumor sizes and TNM clinical stage in HCC patients. Overexpression of
      miR-26a significantly reduced the capacity of proliferation, invasion and
      migration of HCC cells. Moreover, we demonstrated that DNA methyltransferase 3b
      (DNMT3B) was a direct target gene of miR-26a. Overexpression of miR-26a
      suppressed the expression level of DNMT3B. Inhibited expression of DNMT3B showed
      similar tumor suppressive effects induced by miR-26a upregulation, and resulted
      in the upregulation of MEG3. Furthermore, we found that the expression levels of
      DNMT3B were upregulated in the HCC tissues compared with non-malignant tissues,
      and it was inversely correlated with miR-26a and MEG3 in HCC tissues. Thus, these
      results provided a plausible link between the observed reduction of miR-26a and
      MEG3 in HCCs. Together, the present study added miR-26a/DNMT3B/MEG3 axis to the
      complex mechanisms of HCC development.

PMID- 28440440
TI  - Involvement of neurokinin 1 receptor within the cerebrospinal fluid-contacting
      nucleus in visceral pain.
AB  - Studies have shown that the cerebrospinal fluid-contacting nucleus (CSF-CN) may
      be associated with the transduction and regulation of pain signals. However, the
      role of the CSF-CN remains to be elucidated. Emerging evidence has suggested that
      neurokinin 1 receptor (NK1R) is important in the development of visceral pain and
      hyperalgesia, however, whether NK1R exists in the CSF-CN and its exact role in
      visceral pain remain to be fully elucidated. In the present study, double-labeled
      immunofluorescence staining and western blot analysis were performed to
      investigate this. It was revealed that NK1R was distributed in the CSF-CN.
      Following the induction of visceral pain by formalin instillation, NK1R in the
      CSF-CN was upregulated. In addition, by observing the behaviors of rats subjected
      to visceral pain, it was found that visceral pain was relieved by lateral
      intracerbroventricular injection of the NK1R antagonist, RP67580. These data
      provided a broader understanding of the role of NK1R in the CSF-CN and
      demonstrated that the CSF-CN was involved in acute visceral pain via the
      regulation of NK1R.

PMID- 28440441
TI  - Preliminary analysis of the association between methylation of the ACE2 promoter
      and essential hypertension.
AB  - The aim of the present study was to investigate whether methylation of the
      angiotensin I converting enzyme 2 (ACE2) promoter increases the risk of essential
      hypertension (EH). A total of 96 patients with EH were recruited and 96 sex- and
      age-matched healthy controls. Methylation of 5 CpG dinucleotides in the ACE2
      promoter was quantified using bisulfite pyrosequencing. Logistic regression and
      multiple linear regression were used to adjust for confounding factors and the
      generalized multifactor dimensionality reduction (GMDR) method was applied to
      investigate high-order interactions. Methylation of CpG4 (adjusted P=0.020) and
      CpG5 (adjusted P=0.036) was significantly higher in patients with EH, with
      frequency 97.56+/-5.65% and 12.75+/-4.15% in EH individuals and 95.73+/-9.11% and
      11.47+/-3.67% in healthy controls. GMDR detected significant interaction among
      the 5 CpG sites (odds ratio=7.33, adjusted P=0.01). Furthermore, receiver
      operating characteristic curves identified that CpG5 methylation was a
      significant predictor of EH. Notably, CpG2 methylation was significantly higher
      in males than in females (adjusted P=0.018). Conversely, CpG5 methylation was
      significantly lower in males (adjusted P=0.032). These results indicated that
      aberrant methylation of the ACE2 promoter may be associated with EH risk. In
      addition, sex may significantly influence ACE2 methylation.

PMID- 28440442
TI  - Role of the Wnt/beta-catenin signaling pathway in inducing apoptosis and renal
      fibrosis in 5/6-nephrectomized rats.
AB  - Renal fibrosis is the final common pathway of all progressive renal disease.
      Excessive and chronic activation of the Wnt/beta-catenin signaling pathway
      results in chronic kidney disease (CKD) progression. To mimic CKD, the present
      study used 5/6-nephrectomized rats, and alterations in kidney histology,
      expression of beta-catenin and renal cell apoptosis were assessed. In addition,
      mesangial cells were cultured in vitro and transfected with beta-catenin siRNA to
      evaluate the effect of blocking Wnt/beta-catenin signaling on cell apoptosis and
      the expression of markers of renal fibrosis. The results demonstrated that CKD
      rat kidney tissues exhibited moderate renal fibrosis and significantly increased
      expression levels of beta-catenin and apoptosis associated proteins compared with
      sham-operated rats. In vitro, silencing of beta-catenin by siRNA attenuated tumor
      necrosis factor-alpha-induced apoptosis and decreased mRNA expression levels of
      various markers of fibrosis, including fibronectin, transforming growth factor
      beta, and collagen I, III and IV. In conclusion, inhibition of Wnt/beta-catenin
      signaling by beta-catenin silencing attenuated apoptosis and expression of
      fibrosis-associated markers in renal cells. The present study suggested that the
      Wnt/beta-catenin signaling pathway may serve as a potential treatment strategy
      for renal fibrotic disorders.

PMID- 28440443
TI  - MicroRNA expression in esophageal squamous cell carcinoma: Novel diagnostic and
      prognostic biomarkers.
AB  - The aim of the present study was to identify more effective molecular diagnostic
      biomarkers for esophageal squamous cell carcinoma (ESCC). The non-coding RNA
      profile GSE43732, generated from 238 paired frozen tissues from 119 patients, was
      analyzed. Raw data were preprocessed and the differentially expressed miRNAs were
      screened by limma package with log2 fold change >2. Prognosis-associated miRNAs
      were identified using receiver operating characteristic (ROC) and Kaplan-Meier
      (KM) curve analysis. miRNAs with an area under the ROC curve of >=0.7 were
      selected. miRNA target genes were identified from verification and predictive
      databases, and an miRNA regulatory network was constructed and visualized using
      Cytoscape software. Gene Ontology and pathway enrichment analyses of the target
      genes were performed using TargetMine. A total of 107 differentially expressed
      miRNAs, including 54 upregulated and 53 downregulated miRNAs, were obtained. The
      KM survival curves revealed that 44 miRNAs were significantly associated with
      prognosis. Furthermore, 9 upregulated and 3 downregulated miRNAs were obtained.
      Two upregulated miRNAs, hsa-miR-143-3p and hsa-miR-145-5p, and two downregulated
      miRNAs, hsa-miR-182-5p and hsa-miR-455-5p, were identified and demonstrated to be
      associated with prognosis in ESCC. In addition, 8 known and 245 predicted target
      genes of hsa-miR-455-5p were screened and the regulatory networks were
      constructed. Furthermore, these genes were functionally associated with
      macromolecule metabolic process and melanoma. In conclusion, two novel tumor
      suppressive miRNAs including miR-182-5p and miR-455-5p were identified. miR-455
      5p in particular may be involved in the regulation of ESCC. These miRNAs may be
      used to predict the prognosis of ESCC.

PMID- 28440444
TI  - miRNA-556-3p promotes human bladder cancer proliferation, migration and invasion
      by negatively regulating DAB2IP expression.
AB  - MicroRNAs (miRNAs) play critical roles in tumorigenesis and metastasis by
      negatively regulating gene expression through complementary binding to the 3'
      untranslated region of target mRNAs. The role of miRNAs in expression of the
      tumor suppressor DAB2IP in bladder cancer (BC) remains unknown. The aim of the
      present study was to identify miRNAs targeting DAB2IP and determine their
      expression and function in BC. We predicted candidate miRNAs targeting DAB2IP
      using TargetScan software. Dual-luciferase reporter assays confirmed that miRNA
      556-3p directly regulated DAB2IP expression. Quantitative RT-PCR and RNase
      protection assays showed that endogenous miRNA-556-3p expression was
      significantly upregulated in clinical samples of BC patients and BC cell lines
      and western blot analysis indicated that DAB2IP expression in BC tissues and BC
      cell lines was concurrently downregulated. Gain or loss of function studies
      showed that upregulation of miRNA-556-3p promoted proliferation, invasion,
      migration and colony formation of BC cells, whereas downregulation resulted in
      opposite effects. Importantly, restoration of DAB2IP expression rescued the
      effects induced by miRNA-556-3p. Overexpression of miRNA-556-3p in BC cells not
      only decreased DAB2IP expression, but also markedly increased Ras GTPase activity
      and ERK1/2 phosphorylation level. These findings suggest that DAB2IP is a direct
      target of miRNA-556-3p, and endogenous miRNA-556-3p expression shows inverse
      correlation with simultaneous DAB2IP expression in BC tissues and cells. miRNA
      556-3p functions as a tumor promoter in tumorigenesis and metastasis of BC by
      targeting DAB2IP. Moreover, miRNA-556-3p-mediated DAB2IP suppression plays an
      oncogenic role by partial activation of the Ras-ERK pathway.

PMID- 28440445
TI  - miR-196a-5p modulates gastric cancer stem cell characteristics by targeting
      Smad4.
AB  - Cancer stem cells (CSCs) are undifferentiated cancer cells with a high
      tumorigenic activity, the ability to undergo self-renewal, and a multilineage
      differentiation potential. Clinical evidence suggests that CSCs in a tumor mass
      are the cellular determinants to promote cancer invasion and metastasis.
      MicroRNAs (miRNAs) have emerged as important modulators of cancer stem cell
      characteristics. Unveiling the candidate miRNAs that regulate CSCs may provide
      novel therapeutic targets against cancer. We analyzed the miRNA expression
      profiles regulating the cancer stem-like cell characteristics in gastric cancer.
      Gastric cancer stem cells (GCSCs) were sorted using the stem cell marker CD44 by
      fluorescence-activated cell sorting. Functional studies revealed that CD44(+)
      cells formed more sphere colonies and showed higher invasiveness than CD44(-)
      cells. miRNA microarray analysis revealed that miR-196a-5p was significantly
      upregulated in CD44(+) cells than CD44(-) cells. Suppression of miR-196a-5p led
      to decreased colony formation and invasion of GCSCs. miR-196a-5p decreased the
      expression of Smad4 by targeting 3'-UTR of the mRNA. The expression of Smad4 in
      gastric cancer tissues was correlated with differentiation state of tumors, TNM
      stage and depth of invasion. The stimulation of epithelial-mesenchymal transition
      (EMT) by miR-196a-5p in cancer stem-like cells was abolished by overexpression of
      Smad4. Collectively, these data demonstrate that miR-196a-5p has a key role in
      EMT and invasion by targeting Smad4 in GCSCs. miR-196a-5p may serve as a
      potential target for gastric cancer therapy.

PMID- 28440446
TI  - Temporal and spatial changes of monocarboxylate transporter 4 expression in the
      hippocampal CA1 region following transient forebrain ischemia in the Mongolian
      gerbil.
AB  - Transient forebrain ischemia depletes glucose and oxygen levels in the brain. In
      this pathological condition, lactate serves an important role in cellular
      metabolism as the end product of glycolysis. The present study investigated the
      expression of monocarboxylate transporter 4 (MCT4) in lactate metabolism in the
      hippocampal CA1 region following induction of transient forebrain ischemia. MCT4
      immunoreactivity was detected in CA1 pyramidal cells of the sham-operated group.
      Animals from the ischemic group exhibited a transient decrease in MCT4
      immunoreactivity in the CA1 region between 30 min and 3 h following ischemia
      compared with the sham-operated group. The initial decrease in immunoreactivity
      observed between 30 min and 3 h following ischemia was followed by an increase at
      2 days after the treatment. A significant increase in MCT4 immunoreactivity
      levels was observed 2 days after ischemia compared with the sham-operated group.
      Limited MCT4 immunoreactivity was observed in the pyramidal neurons 3 days after
      ischemia. At 4-10 days after ischemia, MCT4 immunoreactivity was detected in the
      strata radiatum, oriens and pyramidale. Furthermore, MCT4 immunoreactivity levels
      in the CA1 region exhibited a time-dependent increase following ischemia. The
      results indicated that there were transient alterations observed in the
      localization of MCT4 following the induction of ischemia, and further studies are
      required to investigate the association between MCT4 expression and lactate
      metabolism in providing energy to the post-ischemic brain.

PMID- 28440447
TI  - Anti-inflammatory effects of oxymatrine on rheumatoid arthritis in rats via
      regulating the imbalance between Treg and Th17 cells.
AB  - Oxymatrine (OMT), a monosomic alkaloid extracted from the Chinese herb, Sophora
      flavescens Ait, has long been used as a traditional Chinese medicine for the
      treatment of inflammatory diseases. The aim of the present study was to
      investigate the potential anti-inflammatory effect of OMT, and its modulation on
      imbalance between regulatory T (Treg) cells and T helper (Th) 17 cells in rats
      with collagen-induced arthritis (CIA). Sprague-Dawley rats were immunized with
      type II collagen and following a second collagen immunization, the rats were
      treated with OMT or dexamethasone (DXM) intraperitoneally once a day for 43 days.
      Paw swelling, arthritic score and joint histopathology were evaluated. The
      Treg/Th17-mediated autoreactive response was assessed by determining serum levels
      of inflammatory response cytokines, including tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-17, using an enzyme-linked immunosorbent assay. The mRNA
      levels of forkhead box P3 (FOXP3) and retinoic acid-related orphan receptor
      (ROR)gammat in spleen cells stimulated with type II collagen were determined
      using reverse transcription-quantitative polymerase chain reaction analysis. In
      addition, the protein expression levels of FOXP3 and RORgammat were measured
      using western blot analysis. The results showed that OMT treatment significantly
      reduced the severity of CIA, markedly abrogating paw swelling, arthritic scores
      and synovial hyperplasia, and the increased loss in body weight. OMT
      significantly reduced the production of TNF-alpha and IL-17A, upregulated FOXP3
      and downregulated RORgammat in rats with CIA. In conclusion, the present study
      demonstrated that OMT exhibited a protective effect on rheumatoid arthritis (RA)
      through the inhibition of inflammation and regulation of Treg/Th17 in the CIA
      rats, suggesting that OMT may be used as an immune suppressive and cartilage
      protective medicine in human RA.

PMID- 28440448
TI  - Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549
      human lung cancer cells.
AB  - Panax ginseng has been used worldwide as a traditional medicine for the treatment
      of cancer and other diseases. The antiproliferative activity of ginseng has been
      increased after enzymatic processing of ginseng saponin, which may result in the
      accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol
      type (PPT) in modified regular ginseng extract (MRGX). In the present study, the
      anticancer activity and the associated mechanisms of MRGX were investigated using
      A549 human lung cancer cells. To elucidate the mechanisms underlying the effects
      of MRGX, we performed a microarray analysis of gene expression in the A549 cells.
      Molecular mechanisms that were associated with the anticancer activity of MRGX
      were studied, with a special focus on the autophagy-related multiple signaling
      pathways in lung cancer cells. Microarray analyses elucidated autophagy-related
      genes affected by MRGX. Administration of MRGX at 100 ug/ml induced punctate
      cytoplasmic expression of LC3, Beclin-1 and ATG5 and increased expression of
      endogenous LC3-II whereas 50 ug/ml did not inhibit the proliferation of A549
      cells. Compared to the control cells, in cells treated with MRGX at 100 ug/ml,
      the level of p-Akt was increased, while that of mTOR-4EBP1 was decreased.
      Downregulation of mTOR and 4EBP1 in the MRGX-treated cells was found not to be a
      p-Ulk (S757)-dependent pathway, but a p-Ulk (S317)-dependent autophagic pathway,
      using AMPK. These data suggest that MRGX regulates AMPK and induces autophagy in
      lung cancer cells.

PMID- 28440449
TI  - Preoperative Tim-3 expression on peripheral NK cells is correlated with
      pathologic TNM staging in colorectal cancer.
AB  - Previous research has indicated that T cell immunoglobulin and mucin domain 3
      (Tim-3) serves an important regulatory role in lymphocytes and in several
      cancers. However, the association between Tim-3 expression on various lymphocyte
      subsets and human colorectal cancer (CRC) has not been elucidated. The present
      study aimed to characterize Tim-3 expression on peripheral lymphocytes, including
      cluster of differentiation CD3+CD56- T cells, CD3-CD56+ natural killer (NK) cells
      and CD3+CD56+ natural killer T (NKT) cells, in patients with CRC. The frequency
      of T cells, NK cells and NKT cells expressing Tim-3 was assessed by multicolor
      flow cytometry of peripheral blood collected from 36 preoperative CRC patients
      and 38 healthy donors. The expression of Tim-3 on lymphocyte subsets from 53
      postoperative blood samples of CRC patients was also analyzed. There were fewer
      circulating NK cells in patients with CRC compared with healthy controls
      (P=0.0027); NK cell expression of Tim-3 was also significantly decreased
      (P=0.0239). The frequency of circulating NK cells and Tim-3+ NK cells was
      negatively correlated with clinical cancer stage, compared with healthy controls,
      but not with other clinicopathological parameters or serum concentrations of CRC
      biomarkers. Furthermore, the expression of Tim-3 in NK cells was higher in CRC
      patients without metastasis. Notably, NK cell Tim-3 expression in CRC patients
      was significantly restored following surgical resection of the primary tumor. In
      conclusion, the present study indicates the presence of an altered frequency and
      expression of Tim-3 in peripheral NK cells in CRC patients. Preoperative Tim-3
      expression on peripheral NK cells is correlated with differential staging in
      colorectal cancer, and may be useful as a serum biomarker.

PMID- 28440451
TI  - PPARdelta activation protects H9c2 cardiomyoblasts from LPS-induced apoptosis
      through the heme oxygenase-1-mediated suppression of NF-kappaB activation.
AB  - The aim of the present study was to investigate the protective effect of the
      selective peroxisome proliferator-activated receptor delta (PPARdelta) agonist
      GW501516 (GW) on lipopolysaccharide (LPS)-induced apoptosis in the rat
      cardiomyoblast cell line H9c2, and to investigate the possible underlying
      mechanisms. Cell viability was estimated using the MTT assay. Apoptosis was
      estimated by flow cytometry using Annexin V-fluorescein isothiocyanate/propidium
      iodide staining and caspase-3 activity assay. The protein level of heme oxygenase
      1 (HO-1), cleaved caspase-3 (CC3), apoptosis regulator Bcl-2 (bcl-2), apoptosis
      regulator BAX (bax) and nuclear factor-kappaB (NF-kappaB) p65 was measured by
      western blot analysis. The results demonstrated that pretreatment with GW
      inhibited the LPS-induced increase in the rate of apoptosis. Pretreatment with GW
      also increased the bcl-2/bax ratio, and decreased CC3 protein expression as well
      as caspase-3 activity, in LPS-stimulated H9c2 cells. Further studies demonstrated
      that GW inhibited LPS-induced NF-kappaB nuclear translocation in a dose-dependent
      manner. In addition, GW induced HO-1 protein expression in a dose-dependent
      manner. ZnPP-IX, an inhibitor of HO-1, reversed the inhibitory effect of GW on
      LPS-induced NF-kappaB activation, leading to the attenuation of PPARdelta
      mediated apoptosis resistance. In conclusion, these results suggest that
      PPARdelta activation exerts an anti-apoptotic effect in LPS-stimulated H9c2
      cardiomyoblasts, potentially through heme oxygenase-1-mediated suppression of NF
      kappaB activation. PPARdelta appears to be a promising therapeutic target for the
      treatment of sepsis-associated cardiac dysfunction.

PMID- 28440450
TI  - Comprehensive analysis of a microRNA expression profile in pediatric
      medulloblastoma.
AB  - Medulloblastoma is the most common malignant brain tumor of the central nervous
      system among children. Medulloblastoma is an embryonal tumor, of which little is
      known about the pathogenesis. Several efforts have been made to understand the
      molecular aspects of its tumorigenic pathways; however, these are poorly
      understood. microRNA (miRNA), a type of non-coding short RNA, has been proven to
      be associated with a number of physiological processes and pathological processes
      of serious diseases, including brain tumors. Differentially expressed miRNAs
      serve an important role in numerous types of malignancy. The present study aims
      to define a differentially expressed set of miRNAs in medulloblastoma tumor
      tissue, compared with normal samples, to improve the understanding of the
      tumorigenesis. It was identified that 22 miRNAs were upregulated and 26 miRNAs
      were downregulated in the tumor tissue compared with the normal group. However,
      when the medulloblastoma tissue was compared with normal cerebellum tissue, 9
      miRNAs were identified to be up or downregulated in the tumor samples. The
      differentially expressed miRNAs in the tumor tissue were identified in order to
      clarify the networks and pathways of tumorigenesis using Ingenuity Pathway
      Analysis. Subsequently, key regulatory genes associated with the development of
      medulloblastoma were identified, including tumor protein p53, insulin like growth
      factor 1 receptor, argonaute 2, mitogen-activated protein kinases 1 and 3,
      sirtuin 1 and Y box binding protein 1.

PMID- 28440452
TI  - BAMBI overexpression together with beta-sitosterol ameliorates NSCLC via
      inhibiting autophagy and inactivating TGF-beta/Smad2/3 pathway.
AB  - Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid
      tumors with a poor prognosis. The BMP and activin receptor membrane bound
      inhibitor (BAMBI) has been identified as a hallmark of NSCLC and beta-sitosterol
      possesses antitumor potentiality. This study explores the effect of BAMBI
      overexpression and beta-sitosterol in the context of NSCLC. The results revealed
      that the transfection of pcDNA-BAMBI and beta-sitosterol treatment significantly
      reduced the levels of autophagy markers light chain 3 (LC3) II and Beclin 1,
      whereas the levels of LC3 I and p62 were promoted. The reduced punctate
      accumulations of GFP-LC3 were detected in pcDNA-BAMBI and beta-sitosterol groups,
      especially in pcDNA-BAMBI + beta-sitosterol group. BAMBI overexpression and beta
      sitosterol induced G0/G1 cell cycle arrest and inhibted cell proliferation in
      A549 cells. In addition, the levels of transforming growth factor-beta (TGF
      beta)/p-Smad2/3/c-Myc pathway proteins were decreased. The TGF-beta
      overexpression further confirmed that BAMBI overexpression and beta-sitosterol
      treatment suppre-ssed autohagy and viability of A549 cells was through TGF
      beta/Smad2/3/c-Myc pathway. Finally, the tumor growth was suppressed in NSCLC
      xenografts, and the inhibitory effect was stronger under treatment of pcDNA-BAMBI
      toge-ther with beta-sitosterol. These results indicate that BAMBI overexpression
      and beta-sitosterol may serve as novel targets for the treatment of NSCLC.

PMID- 28440454
TI  - MicroRNA-336 directly targets Sox-2 in osteosarcoma to inhibit tumorigenesis.
AB  - Previous evidence has suggested that microRNAs (miRNAs or miRs), which belong to
      a class of non-coding RNAs, shape cellular processes by regulating gene
      expression. Abnormal expression of miRNAs has been associated with tumorigenesis
      in multiple cancers. However, the function of miR-336 in osteosarcoma (OS)
      remains unknown. The experimental procedures used in the present study included
      flow cytometry, reverse transcription-quantitative polymerase chain reaction,
      luciferase reporter assay, invasion assay, western blot analysis and in vivo
      implantation. The results of the present study demonstrated that miR-336 may
      serve as a tumor suppressor in OS. Downregulation of miR-336 was observed in
      human OS specimens as well as OS cell lines. In addition, a significant negative
      correlation between sex determining region Y-box 2 (Sox-2) expression and miR-336
      was demonstrated. miR-336 was confirmed to target the 3'-untranslated region of
      Sox-2 to inhibit proliferation, migration and invasion of OS cells. Consistently,
      restoration of Sox-2 expression counteracted the effect of miR-336, and recovered
      the tumorigenic potential of OS cells. The present study established a novel
      association between miR-336 and Sox-2 in OS. This relationship between miR-336
      and Sox-2 may lead to improved knowledge concerning OS progression and sheds
      light on potential novel therapeutic interventions for OS treatment.

PMID- 28440453
TI  - SCRG1 suppresses LPS-induced CCL22 production through ERK1/2 activation in mouse
      macrophage Raw264.7 cells.
AB  - Recently, we identified the scrapie responsive gene 1 (SCRG1) secreted from
      mesenchymal stem cells (MSCs) and its receptor bone marrow stromal cell antigen 1
      (BST1) as positive regulators of stem cell qualities such as self-renewal,
      migration abilities, and osteogenic differentiation potential. Here, we examined
      the effect of the paracrine activity of SCRG1 in macrophages. The mouse
      macrophage-like cell line Raw264.7 expressed BST1/beta1 or BST1/beta2 integrin as
      possible SCRG1 receptors. Unexpectedly, recombinant SCRG1 did not enhance cell
      proliferation, migration, or adhesion in these macrophages. However, further
      examination of the effect of SCRG1 in Raw264.7 cells did reveal a potent anti
      inflammatory effect whereby SCRG1 suppressed LPS-induced CCL22 production. SCRG1
      also induced the phosphorylation of extracellular signal-regulated kinase 1/2
      (ERK1/2) in these cells and, moreover, a mitogen-activated protein kinase
      (MAPK)/ERK kinase inhibitor U0126 significantly suppressed the effect of SCRG1 on
      LPS-induced chemokine CCL22 production. Taken together, these data indicate that
      SCRG1 signals through the MAPK pathway and suppresses the LPS signaling pathway.
      CCL22 is generally known to be chemotactic for monocytes, dendritic cells,
      natural killer cells and chronically activated T lymphocytes, suggesting that MSC
      derived SCRG1 may block infiltration of these cells. A mechanism is proposed by
      which MSCs play their immunosuppressive role through suppressing chemokine
      expression in monocyte/macrophage lineage cells.

PMID- 28440455
TI  - alpha-adrenoceptor-mediated enhanced inducibility of atrial fibrillation in a
      canine system inflammation model.
AB  - The exact mechanism associated with inflammation and atrial fibrillation (AF)
      remains unknown. The aim of the present study was to investigate the roles of
      connexin 43 (Cx43) and a1-adrenergic receptor (alpha1-AR) activation in the
      pathogenesis of system inflammation-induced AF. A canine model of chronic low
      grade system inflammation was established by administrating a low dose of
      lipopolysaccharide (LPS; 0.1 ug/kg) for 2 weeks. Programmed stimulation was
      applied on the right atrial appendage to determine the effective refractory
      periods (ERP) and the window of vulnerability (WOV). Tumor necrosis factor alpha
      (TNF-alpha) and interleukin 6 (IL-6) levels in plasma and atrial tissue were
      measured by ELISA. Cx43, Toll-like receptor 4 (TLR4) and nuclear factor kappaB
      (NF-kappaB) proteins were analyzed using western blotting or
      immunohistochemistry. Administration of LPS for 2 weeks increased the
      concentration of TNF-alpha and IL-6 in the plasma and right atrium. ERP was
      markedly shortened and cumulative WOV was significantly widened in the LPS group.
      Following treatment with LPS, the amount of Cx43 protein in the area of
      intercalated disk increased. In addition, a high-density of Cx43 in the lateral
      connection was identified. LPS also induced the activation of NF-kappaB in the
      canine atrium. Administration with the alpha1-AR blocker doxazosin prevented the
      production of LPS-induced inflammatory cytokine and reversed the enhanced
      vulnerability to atrial fibrillation. Doxazosin inhibited the LPS-induced
      increase in Cx43 protein and heterogeneous distribution, and prevented the
      activation of NF-kappaB. These results indicated that chronic low-grade system
      inflammation may increase the inducibility of AF in a canine model. The
      underlying mechanism may be involved in the LPS-induced activation of NF-kappaB,
      and the increase in Cx43 expression and lateral distribution via an alpha1-AR
      dependent pathway.

PMID- 28440456
TI  - Tetrahydropalmatine inhibits lipid accumulation through AMPK signaling pathway in
      3T3-L1 adipocytes.
AB  - Tetrahydropalmatine (THP), one of the active components of Rhizoma corydalis, has
      been reported to exert several pharmacological effects, including anti
      inflammatory, anti-tumor and analgesic activities. However, its effect on obesity
      and the underlying molecular mechanisms that may be involved have not yet been
      elucidated. In the present study, the inhibitory effects of THP on the
      adipogenesis in 3T3-L1 adipocytes was examined using hstology, western blotting
      and RT-qPCR. THP was identified to significantly suppress lipid accumulation in
      3T3-L1 cells and it inhibited pre-adipocyte differentiation in a concentration
      dependent manner, as evidenced by the reduced formation of lipid droplets and
      decreased triglyceride levels and glycerol-3-phosphate dehydrogenase activity.
      THP downregulated the adipogenesis-associated protein and gene expressions of
      sterol regulatory element-binding protein 1, fatty acid synthase, stearoyl-CoA
      desaturase 1, peroxisome proliferator activated receptor gamma and CCAAT/enhancer
      binding protein-alpha in a concentration-dependent manner. In addition, it
      reduced adipocyte fatty acid binding protein and glycerol-3-phosphate
      acyltransferase gene expression in a concentration-dependent manner. Conversely,
      THP increased the mRNA expression of carnitine palmitoyltransferase 1 in a
      concentration-dependent manner. Furthermore, THP increased AMP-activated protein
      kinase (AMPK) and acetyl-CoA carboxylase phosphorylation in a concentration
      dependent manner. These results suggested that anti-adipogenic activity of TPH
      may be mediated via the AMPK pathway in 3T3-L1 cells.

PMID- 28440457
TI  - beta-catenin induces expression of prohibitin gene in acute leukemic cells.
AB  - Prohibitin (PHB) is a multifunctional protein conserved in eukaryotic systems and
      shows various expression levels in tumor cells. However, regulation of PHB is not
      clearly understood. Here, we focused on the regulation of PHB expression by Wnt
      signaling, one of dominant regulatory signals in various leukemic cells. High
      mRNA levels of PHB were found in half of clinical leukemia samples. PHB
      expression was increased by inhibition of the MAPK pathway and decreased by
      activation of EGF signal. Although cell proliferating signals downregulated the
      transcription of PHB, treatment with lithium chloride, an analog of the Wnt
      signal, induced PHB level in various cell types. We identified the TCF-4/LEF-1
      binding motif, CATCTG, in the promoter region of PHB by site-directed mutagenesis
      and ChIP assay. This beta-catenin-mediated activation of PHB expression was
      independent of c-MYC activation, a product of Wnt signaling. These data indicate
      that PHB is a direct target of beta-catenin and the increased level of PHB in
      leukemia can be regulated by Wnt signaling.

PMID- 28440458
TI  - Role of the cystathionine beta-synthase/H2S system in liver cancer cells and the
      inhibitory effect of quinolone-indolone conjugate QIC2 on the system.
AB  - Hydrogen sulfide (H2S), the third gasotransmitter, plays important roles in
      cancer biological processes. As endogenous H2S exerts pro-cancer functions,
      inhibition of its production in cancer cells may provide a new cancer treatment
      strategy and be achieved via regulation of the function of cystathionine beta
      synthase (CBS), one of the main metabolic enzymes synthesizing H2S. This enzyme
      plays important roles in the development and progression of colon and ovarian
      cancer, primarily regulating mitochondrial bioenergetics and accelerating cell
      cycle progression. In the present study, we firstly investigated the role of the
      CBS/H2S system in human hepatoma cells, and then the inhibitory effect of a
      quinolone-indolone conjugate QIC2 on this system. When CBS was overexpressed in
      human hepatoma HepG2 and SMMC-7721 cells, inhibition of endogenous CBS/H2S
      significantly reduced their viability and growth rate, as well as the
      proliferation of SMMC-7721 cells. Meanwhile, CBS knockdown caused multiple
      effects, including apoptosis of SMMC-7721 cells, an increase in the Bcl-2
      associated X protein (Bax)/B cell lymphoma/leukemia (Bcl-2) ratio, activation of
      caspase-3 and polyADP-ribose polymerase (PARP), when compared with the scramble
      siRNA (Sc siRNA)-transfected groups. Heme oxygenase-1 (HO-1; a microsomal enzyme)
      expression was significantly decreased while the reactive oxygen species (ROS)
      level was increased in the CBS siRNA-transfected SMMC-7721 cells. QIC2
      significantly reduced SMMC-7721 cell viability in a dose-dependent manner and
      showed a lower toxicity in human normal liver HL-7702 cells relative to the
      positive controls sunitinib and doxorubicin (DOX). The compound also inhibited
      cell proliferation and induced cell apoptosis in SMMC-7721 cells. Further
      analysis indicated that QIC2 downregulated the CBS/H2S system, decreased both HO
      1 protein and glutathione (GSH) levels while increased the ROS level and
      activated the caspase-3 cascade. Collectively, our results demonstrated that the
      CBS/H2S system plays important roles in human hepatoma cells and QIC2
      significantly inhibited cell growth via downregulation of the system.

PMID- 28440459
TI  - Hypoxia-induced miR-210 promoter demethylation enhances proliferation, autophagy
      and angiogenesis of schwannoma cells.
AB  - Hypoxia, a dominant feature in cancer occurrence and evolution, exists throughout
      the progression of most malignant tumors. This study focused on the mechanism of
      hypoxia-induced miR-210 upregulation, and the miR-210 functions in schwannoma. We
      detected microvascular density, vascular endothelial growth factor (VEGF) and miR
      210 expression levels using schwannoma tissue mciroarray. The results showed that
      miR-210 expression was significantly associated with VEGF. Moreover, the
      cytological tests showed that hypoxia induced miR-210 expression, while reduce
      ephrin-A3 expression. The bisulfate genomic sequencing PCR results showed that
      miR-210 promoter region was hypermethylated in RT4-D6P2T in normoxia, while
      demethylated in hypoxia, and the region included the hypoxia-inducible factor
      1alpha (HIF-1alpha) response element site. Cellular function research showed that
      hypoxia resulted in RT4-D6P2T apoptosis, higher autophage and invasion. Besides,
      hypoxia can affect HIF-1alpha/VEGF-mediated angiogenesis. To learn about the
      specific functions of miR-210, we found that with miR-210 inhibition, tumor cell
      apoptosis increased, autophagy and angiogenesis reduced, and the cell cycle was
      arrested. Hypoxia promoted miR-210 expression through promoter demethylation,
      then consequently enhanced tumor cell proliferation and autophagy, increasing
      tumor cell angiogenesis. Thus, miR-210 could be a potential marker for judging
      tumor malignancy and be taken as an effective target for clinical auxiliary
      treatment of neurilemmoma.

PMID- 28440460
TI  - Triple-negative breast cancer: New therapeutic options via signalling
      transduction cascades.
AB  - Triple-negative breast cancer is a highly aggressive type of mammalian carcinoma.
      It is defined by a rather weak expression of estrogen-, progesterone- and Her2
      receptor, and is thus difficult to treat, resulting in low disease-free and
      overall survival rates of the affected patients. Hence it is important to find
      new therapeutic options. To this aim we analysed the incidence of some molecules
      from different signal transduction cascades by immunohistochemistry, which are
      known to correlate with triple-negative breast cancer, and correlated the
      expression of these molecules to different tumour traits, such as size, grading,
      menopausal stage, histology, lymph node affection, remote metastasis formation,
      and to the incidence of local and lymph node recurrence and metastasis by
      statistical analysis. Statistically significant correlations were found for a
      number of tumour characteristics and signalling molecules: HIF1alpha is
      correlated to tumour grading, beta-catenin to the menopausal state of the
      patient, and for Notch1 a relation to lymph node affection is seen. In terms of
      different recurrences, a correlation of beta-catenin to metastasis formation and
      lymph node affection could be shown, as well as coherences between XBP1 and lymph
      node recurrence, Notch1 and metastasis formation and FOXP3 and the occurrence of
      local recurrence. The presented results are in accordance with formerly published
      studies and therefore might comprise opportunities to develop new therapeutical
      strategies, which could help to handle this aggressive form of breast cancer in a
      manner, by which side effects would be reduced and therapeutical efficiency is
      increased.

PMID- 28440462
TI  - Imperatorin efficiently blocks TNF-alpha-mediated activation of ROS/PI3K/Akt/NF
      kappaB pathway.
AB  - Inflammation contributes to development and progression in a variety of cancers,
      including cervical cancer, which is the second leading cause of cancer deaths in
      women worldwide. In this study, we examined the anti-inflammatory effects of
      imperatorin, a psoralen-type furanocoumarin from the fruits of Angelica dahurica,
      in tumor necrosis factor-alpha (TNF-alpha)-stimulated HeLa cells by investigating
      its impact on the production and expression of cytokines and the major signal
      transduction pathways. We found this compound significantly inhibited the TNF
      alpha-induced expression of NF-kappaB target genes, such as COX-2, cyclin  D1,
      MMP-9, VEGF, IL-6 and Bcl-xL in a concentration-dependent manner. Further
      analysis revealed that imperatorin was a potent inhibitor of NF-kappaB activation
      by the suppression of TNF-alpha-induced IKKalpha/beta phosphorylation, IkappaB
      phosphorylation and degradation, and NF-kappaB p65 nuclear translocation. We also
      demonstrated that imperatorin downregulated TNF-alpha-induced activation of
      PI3K/Akt. Furthermore, our findings show that imperatorin inhibits TNF-alpha
      induced ROS generation. Taken together, imperatorin can blunt inflammation by
      inhibiting the ROS-mediated activation of the PI3K/Akt/NF-kappaB pathway.

PMID- 28440463
TI  - Livin enhances chemoresistance in head and neck squamous cell carcinoma.
AB  - The responsiveness of head and neck squamous cell carcinoma (HNSCC) to
      chemotherapy widely affects prognosis. Overcoming chemoresistance is necessary to
      improve prognoses in patients with advanced HNSCC. Evasion of apoptosis by cancer
      cells is a major cause of chemoresistance. Livin, a member of the human
      inhibitors of apoptosis protein family, is highly expressed in various human
      cancer tissues and is associated with tumor progression and poor prognosis in
      human cancers. The aim of the present study was to evaluate the role of Livin in
      the susceptibility to popularly used chemotherapeutic drugs such as cisplatin, 5
      fluorouracil (FU) and docetaxel in human HNSCC cell lines (SNU1041, PCI1 and
      PCI50 cells). Reverse transcription polymerase chain reaction and western
      blotting were performed to determine mRNA and protein expression levels. Cell
      viability and apoptosis assays were used to assess the functional effects of
      small-interfering RNA-mediated knockdown of Livin. Each HNSCC cell line had
      different sensitivity to chemotherapeutic drugs. Livin knockdown significantly
      enhanced cytotoxicity to cisplatin, 5-FU and docetaxel in human HNSCC cells.
      Livin knockdown induced apoptosis and enhanced chemotherapy-induced apoptosis to
      cisplatin, 5-FU and docetaxel. Consistent with this, Livin-knockdown cells showed
      greater expression of cleaved caspases-3 and -7 and poly(ADP-ribose)polymerase
      compared with that in control cells after cisplatin, 5-FU, or docetaxel
      treatment. In conclusion, our results suggest that siRNA-mediated Livin knockdown
      enhanced the chemosensitivity of the three HNSCC cell lines to cisplatin, 5-FU
      and docetaxel. Although further investigations are required to support these
      findings, our results demonstrated that novel therapeutic strategies with
      combined use of siRNA targeting Livin and chemotherapeutic agents may have
      applications in the treatment of advanced HNSCC.

PMID- 28440461
TI  - The role of miR-451 in the switching between proliferation and migration in
      malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation
      required.
AB  - Glioblastoma multiforme (GBM), WHO grade IV astrocytoma, is the most common
      primary neoplasm of the central nervous system (CNS) and has the highest
      malignancy and mortality rates. The invasive nature of GBM complicates surgical
      resection and restricts chemotherapeutic access, contributing to poor patient
      prognosis. The migration of tumor cells is closely related to the tumor cell
      proliferation. The acquisition of migratory capability, in addition to
      intracellular factors, is proposed to be a crucial mechanism during the
      progression of invasion. Using qRT-PCR analysis, we determined that the
      expression of miR-451 in glioma tissue was lower than in control brain tissue,
      especially in the central portions of the tumor. In glioma cell lines, we found
      that decreased miR-451 expression suppressed tumor cell proliferation but
      enhanced migration with a concomitant low level of CAB39/AMPK/mTOR pathway
      activation and high level of Rac1/cofilin pathway activation, respectively.
      Notably, the effect of miR-451 on cytological behavior and on the activation of
      mTOR and Rac1 was limited when AMPKalpha1 expression was knocked-down with a
      synthetic shRNA. We suggest that the glioma microenvironment results in
      heterogeneity of miR-451 expression. Our data indicated that miR-451 relays
      environmental signals by upregulating the activity of AMPK signaling, thereby
      modulating the activation of mTOR and Rac1/cofilin which, in turn, play key roles
      in glioma cell proliferation and migration, respectively. Our results highlight
      the need to consider opposing roles of a therapeutic target which, while
      suppressing tumor cell proliferation, could also promote cell infiltration.

PMID- 28440465
TI  - 5-(Furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3-one oxime (6f), a new
      synthetic compound, causes human fibrosarcoma HT-1080 cell apoptosis by
      disrupting tubulin polymerisation and inducing G2/M arrest.
AB  - In the current study, we synthesized a series of new compounds targeting tubulin
      and tested their anti-proliferative activities. Among these new synthetic com
      pounds, 5-(furan-2-yl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiol-3-one oxime (6f)
      exhibited significant anti-proliferative activity against different human cancer
      cell lines including human gastric adenocarcinoma SGC-7901, human non-small cell
      lung cancer A549, and human fibrosarcoma HT-1080. As a result, 6f was selected to
      further test the sensitivity to different cancer cell lines including human
      cervical cancer cell line HeLa, human breast cancer cell line MCF-7, non-small
      cell lung cancer cell line A549, human liver carcinoma cell line HepG-2, human
      oral squamous cell carcinoma cell lines KB, SGC-7901 and HT-1080. Among these
      cell lines, HT-1080 and HeLa are the most sensitive. Therefore, HT-1080 was
      selected to further explore the properties of anti-proliferative activity and the
      underlying mechanisms. Our data proved that 6f exhibited strong anti
      proliferative effects against HT-1080 cells in a time- and dose-dependent manner.
      We showed that the growth inhibitory effect of 6f in HT-1080 cells was related
      with microtubule depolymerisation. Molecular docking studies revealed that 6f
      interacted and bound efficiently with the colchicine-binding site of tubulin. In
      addition, 6f treatment induced G2/M cell cycle arrest dose-dependently and
      subsequently induced cell apoptosis. Western blot study indicated that
      upregulation of cyclin B1 and p-cdc2 was related with G2/M arrest. 6f-induced
      cell apoptosis was associated with both mitochondrial and death receptor pathway.
      In conclusion, our data showed that 6f, among the newly synthetic compounds,
      exhibited highest anti-proliferative activity by disrupting the microtubule
      polymerisation, causing G2/M arrest and subsequently inducing cell apoptosis in
      HT-1080 cells. Hence, 6f is a promising microtubule depolymerising agent for the
      treatment of various cancers especially human fibrosarcoma.

PMID- 28440464
TI  - Proteomic profiling of mdx-4cv serum reveals highly elevated levels of the
      inflammation-induced plasma marker haptoglobin in muscular dystrophy.
AB  - X-linked muscular dystrophy is caused by primary abnormalities in the Dmd gene
      and is characterized by the almost complete loss of the membrane cytoskeletal
      protein dystrophin, which triggers sarcolemmal instability, abnormal calcium
      homeostasis, increased proteolysis and impaired excitation-contraction coupling.
      In addition to progressive necrosis, crucial secondary pathologies are
      represented by myofibrosis and the invasion of immune cells in damaged muscle
      fibres. In order to determine whether these substantial changes within the
      skeletal musculature are reflected by an altered rate of protein release into the
      circulatory system or other plasma fluctuations, we used label-free mass
      spectrometry to characterize serum from the mdx-4cv model of Duchenne muscular
      dystrophy. Comparative proteomics revealed a large number of increased vs.
      decreased protein species in mdx-4cv serum. A serum component with greatly
      elevated levels was identified as the inflammation-inducible plasma marker
      haptoglobin. This acute phase response protein is usually secreted in relation to
      tissue damage and sterile inflammation. Both immunoblot analyses and enzyme
      linked immunosorbent assays confirmed the increased concentration of haptoglobin
      in crude mdx-4cv serum. This suggests that haptoglobin, in conjunction with other
      altered serum proteins, represents a novel diagnostic, prognostic and/or therapy
      monitoring biomarker candidate to evaluate the inflammatory response in the mdx
      4cv animal model of dystrophinopathy.

PMID- 28440466
TI  - miR-200a targets Gelsolin: A novel mechanism regulating secretion of
      microvesicles in hepatocellular carcinoma cells.
AB  - Microvesicle biogenesis is a highly regulated process. Aberrant release of
      microvesicles from cancer cells have been associated with their invasiveness and
      prognosis. However, the mechanism of aberrant release remains poorly understood.
      Herein, we found that hepatocellular carcinoma cells shed more microvesicles than
      normal hepatocytes and miR-200a were shown to inhibit the release of
      microvesicles in hepatocellular carcinoma cells. Then, we confirmed that miR-200a
      might target Gelsolin and change cytoskeleton to regulate microvesicles
      secretion. Further miR-200a may inhibit the proliferation of adjacent cells by
      inhibiting the release of microvesicles. Collectively, our findings indicate that
      miR-200a regulated the microvesicle biogenesis involved in the hepatocellular
      carcinoma progression.

PMID- 28440467
TI  - Structural and evolutionary divergence of aquaporins in parasites (Review).
AB  - Aquaporins are ubiquitous proteins that belong to the major intrinsic protein
      family. Previous studies have indicated that aquaporins are involved in multiple
      physiological processes in parasites, such as nutrient absorption and end product
      efflux, and thus, would be promising pharmacological agents in the fight against
      parasite infection. In the present paper, the authors analyzed the evolutionary
      relationship of parasitic aquaporins by re-constructing of a phylogenic tree
      using neighbor-joining and maximum likelihood methods. In addition, the authors
      discussed the variation of the conserved functional sites impacting on the
      transportation of water molecules. The protein was concluded to be a potential
      drug target in parasites.

PMID- 28440468
TI  - Vitamin D attenuates hyperoxia-induced lung injury through downregulation of Toll
      like receptor 4.
AB  - With considerable morbidity and mortality, bronchopulmonary dysplasia (BPD) is a
      focus of attention in neonatology. Hyperoxia-induced lung injury has long been
      used as a model of BPD. Among all the signaling pathways involved, Toll-like
      receptor 4 (TLR4) has been demonstrated to play an important role, and is known
      to be regulated by vitamin D. This study aimed at elucidating the effect of
      vitamin D on hyperoxia-induced lung injury and the role of TLR4 in the process.
      Vitamin D was administered to hyperoxia-treated neonatal rats to investigate
      changes in the morphology of lungs and expression of pro-inflammatory cytokines,
      apoptotic proteins and TLR4. Vitamin D attenuated hyperoxia-induced lung injury
      by protecting the integrity of the lung structure, decreasing extracellular
      matrix deposition and inhibiting inflammation. The upregulation of TLR4 by
      hyperoxia was ameliorated by vitamin D and apoptosis was reduced. Vitamin D
      administration antagonized the activation of TLR4 and therefore alleviated
      inflammation, reduced apoptosis and preserved lung structure.

PMID- 28440469
TI  - Clinical significance of Akt2 in advanced pancreatic cancer treated with
      erlotinib.
AB  - Akt2 is an isoform of Akt, and an association between Akt2 and resistance to
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has
      been suggested in pancreatic cancer (PC) in vitro. In this study, we investigated
      the association between Akt2 expression as evaluated using immunohistochemistry
      and the outcome of patients with advanced PC who had received treatment with
      erlotinib (an EGFR-TKI). Although the difference was not significant, patients
      with high levels of Akt2 expression tended to have a poorer response and a
      shorter progression-free survival period after treatment with erlotinib plus
      gemcitabine than those with low expression levels (P=0.16 and 0.19,
      respectively). In vitro, an Akt2-amplified PC cell line and Akt2-overexpressed
      cell lines exhibited resistance to anti-EGFR therapies, including erlotinib, but
      combined treatment with BYL719 (a PI3K inhibitor) cancelled this resistance. Our
      findings suggest that Akt2 might be associated with the resistance to anti-EGFR
      therapies, especially the use of erlotinib against PC, and that this resistance
      can be overcome by combined treatment with a PI3K inhibitor. Akt2 expression
      could become a predictive biomarker for erlotinib resistance in PC.

PMID- 28440470
TI  - Proliferation and differentiation of direct co-culture of bone marrow mesenchymal
      stem cells and pigmented cells from the ciliary margin.
AB  - Damage of retinal ganglion cells (RGCs) is the major consequence of glaucoma and
      regeneration of RGCs is extremely difficult once the damage has occurred. Retinal
      stem cells (RSCs) are considered an ideal choice for RGC regeneration. Pigmented
      cells from the ciliary margin (PCMs) have great retinal differentiation potential
      and may be an ideal RSC candidate. However, the ciliary margin is too small, so
      the number of cells that can be obtained is limited. Bone marrow-derived
      mesenchymal stem cells (BMMSCs) are another type of stem cell that have been
      previously investigated for RGC regeneration. BMMSCs expand sufficiently, whereas
      the retinal differentiation of BMMSCs is insufficient. The aim of the present
      study was to investigate whether the co-culture of PCMs and BMMSCs may combine
      the advantages of both cell types to establish a novel and effective stem cell
      source for RGC regeneration. Primary rat PCMs and BMMSCs were isolated and co
      cultured. Cell growth was observed by an inverted microscope and proliferation
      was monitored by an MTT assay. Cell cycle analysis was performed by using a flow
      cytometer, while the expression of the photoreceptor-specific homeobox gene (cone
      rod homeobox, Crx) was determined by reverse transcription-quantitative
      polymerase chain reaction and western blot analysis. In addition, retinal
      differentiation was confirmed by immunofluorescence staining of major markers of
      retinal differentiation, including rhodopsin, visual system homeobox 2 and
      heparin sulfate. The co-cultured cells expanded successfully, in a similar way to
      BMMSCs. In addition, the expression of Crx and retinal markers were significantly
      upregulated following BMMSC and PCM co-culture. The results of the present study
      demonstrated that the co-culture of BMMSCs and PCMs may be used as a source of
      RSCs.

PMID- 28440471
TI  - Time-dependent differential expression of long non-coding RNAs following
      peripheral nerve injury.
AB  - Long non-coding RNAs (lncRNAs) are widely accepted as key players in various
      biological processes. However, the roles of lncRNA in peripheral nerve
      regeneration remain completely unknown. Thus, in this study, we performed
      microarray analysis to measure lncRNA expression in the distal segment of the
      sciatic nerve at 0, 3, 7 and 14 days following injury. We identified 5,354
      lncRNAs that were differentially expressed: 3,788 lncRNAs were differentially
      expressed between days 0 and 3; 3,314 lncRNAs were differentially expressed
      between days 0 and 7; and 2,400 lncRNAs were differentially expressed between
      days 0 and 14. The results of RT-qPCR of two dysregulated lncRNAs were consistent
      with those of microarray analysis. Bioinformatics approaches, including lncRNA
      classification, gene ontology (GO) analysis and target prediction, were utilized
      to investigate the functions of these dysregulated lncRNAs in peripheral nerve
      damage. Importantly, we predicted that several lncRNA-mRNA pairs may participate
      in biological processes related to peripheral nerve injury. RT-qPCR was performed
      for the preliminary verification of three lncRNA-mRNA pairs. The overexpression
      of NONMMUG014387 promoted the proliferation of mouse Schwann cells. Thus, the
      findings of our study may enhance our knowledge of the role of lncRNAs in nerve
      injury.

PMID- 28440472
TI  - Human umbilical cord mesenchymal stem cells alleviate acute myocarditis by
      modulating endoplasmic reticulum stress and extracellular signal regulated 1/2
      mediated apoptosis.
AB  - Acute myocarditis is a non-ischemic inflammatory disease of the myocardium, and
      there is currently no standard treatment. Mesenchymal stem cells (MSCs) can
      alleviate myosin-induced myocarditis; however, the mechanism has not been clearly
      elucidated. In the present study, the authors investigated the ability of human
      umbilical cordMSCs (HuMSCs) to attenuate myocardial injury and dysfunction during
      the acute phase of experimental myocarditis. Male Lewis rats (aged 8 weeks) were
      injected with porcine myosin to induce myocarditis. Cultured HuMSCs (1x106
      cells/rat) were intravenously injected 10 days following myosin injection. A
      total of 3 weeks following injection, this resulted in severe inflammation and
      significant deterioration of cardiac function. HuMSC transplantation attenuated
      infiltration of inflammatory cells and adverse cardiac remodeling, as well as
      reduced cardiomyocyte apoptosis. Furthermore, it was identified that HuMSC
      transplantation suppressed endoplasmic reticulum stress and extracellular signal
      regulated kinase (ERK)1/2 signaling in experimental autoimmune myocarditis (EAM).
      The reduced number of TUNEL-positive apoptotic cells in myocardial sections from
      HuMSC-treated EAM rats compared with control demonstrates HuMSCs' anti-apoptotic
      function. Based on these data, the author suggested that treatment with HuMSCs
      inhibits myocardial apoptosis in EAM rats, ultimately protecting them from
      myocardial damage. The conclusion demonstrated that HuMSC transplantation
      attenuates myocardial injury and dysfunction in a rat model of acute myocarditis,
      potentially via regulation of ER stress, ERK1/2 signaling and induction of
      cardiomyocyte apoptosis.

PMID- 28440473
TI  - CXCR6 predicts poor prognosis in gastric cancer and promotes tumor metastasis
      through epithelial-mesenchymal transition.
AB  - Chemokines and their receptors have been confirmed to be involved in several
      types of cancer. However, little is known concerning the role of CXCL16 and its
      receptor CXCR6 in gastric cancer (GC) progression and metastasis. In the present
      study, expression of CXCL16 and CXCR6 in GC tumor and peritumoral tissues was
      detected by immunohistochemistry (IHC) in a cohort of 352 GC patients who
      underwent gastrectomy, and the correlation between CXCL16/CXCR6 expression and
      clinicopathological characteristics was further analyzed. To evaluate the
      function of CXCR6, we overexpressed and knocked down CXCR6 in GC cell lines.
      Results showed that expression of CXCR6, but not CXCL16, was significantly
      upregulated in GC tumor tissues, and was significantly correlated with lymph node
      and distant metastases, and advanced clinical stage in the GC patients. Survival
      analysis showed that large tumor size (>5 cm), elevated preoperative serum
      carcinoembryonic antigen (CEA) level, advanced TNM stage and high CXCR6
      expression indicated worse overall survival (OS) and disease-free survival (DFS)
      in GC, and CXCR6 was an independent predictor for both OS and DFS in GC. In vitro
      experiments showed that CXCR6 overexpression induced cell migration and invasion
      ability, and promoted epithelial-mesenchymal transition of GC cells by
      upregulation of mesenchymal markers and inhibition of epithelial markers. In
      contrast, knockdown of CXCR6 in GC cells resulted in inhibition of cell
      proliferation, migration and invasion ability, and reversal of epithelial
      mesenchymal transition (EMT) phenomenon. Our results demonstrated that CXCR6 is
      an independent prognostic factor for poor survival in GC patients, and may
      promote GC metastasis through EMT.

PMID- 28440475
TI  - A nine-miRNA signature as a potential diagnostic marker for breast carcinoma: An
      integrated study of 1,110 cases.
AB  - Growing evidence indicates that microRNAs (miRNAs) play critical roles in the
      initiation and progression of breast carcinoma (BC) and are promising diagnostic
      biomarkers. In the present study, we aimed to identify a multi-marker miRNA pool
      with high diagnostic performance for BC. We collected miRNA expression profiles
      of BC samples and normal breast tissues from The Cancer Genome Atlas (TCGA) and
      screened differentially expressed miRNAs by conducting two-sample t-tests and by
      calculating log2 fold-change (log2FC) ratios. Statistical significance was
      established at p<0.001 and |log2FC| >1. Then, we generated receiver operating
      characteristic (ROC) curves, calculated the area under the curve (AUC) with a 95%
      confidence interval (95% CI), and calculated the diagnostic sensitivity and
      specificity using MedCalc software. Additionally, we predicted the targets of
      candidate miRNAs using 10 online databases: TarBase, miRTarBase, TargetScan,
      TargetMiner, microRNA.org, RNA22, PicTar-vert, miRDB, PITA and PolymiRTS. Target
      genes that were predicted by at least four algorithms were chosen, and
      cooperative targets of multiple miRNAs were further selected for GO and KEGG
      pathway analyses through the DAVID online tool. Eventually, a total of 66
      differentially expressed miRNAs were identified after miRNA expression profiles
      were analyzed in BC and normal breast samples. Of these, we selected nine
      dysregulated miRNAs as candidate diagnostic markers: seven upregulated miRNAs
      (hsa-miR-21, hsa-miR-96, hsa-miR-183, hsa-miR-182, hsa-miR-141, hsa-miR-200a and
      hsa-miR-429) and two downregulated miRNAs (hsa-miR-139 and hsa-miR-145). The ROC
      curve for the combination of these nine differently expressed miRNAs showed
      extremely high diagnostic accuracy, with an AUC of 0.995 (95% CI, 0.988-0.999)
      and diagnostic sensitivity and specificity of 98.7 and 98.9%, respectively. In
      conclusion, the combination of these nine miRNAs significantly improved the
      accuracy of breast cancer diagnosis.

PMID- 28440474
TI  - Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic
      endothelial cell proliferation, migration and tube formation.
AB  - Kallistatin has been recognized as an endogenous angiogenic inhibitor. However,
      its effects on lymphatic endothelial cells and lymphangiogenesis remain poorly
      understood. Lymphangiogenesis is involved in tumor metastasis via the lymphatic
      vasculature in various types of tumors. The aim of this study was to investigate
      the effects of kallistatin on lymphangiogenesis and the mechanism of action
      involved. Treatment with kallistatin recombinant protein or overexpression of
      kallistatin inhibited the proliferation, migration and tube formation of human
      lymphatic endothelial cells (hLECs), and induced apoptosis of hLECs. Furthermore,
      our results showed that the lymphatic vessel density (LVD) was reduced in lung
      and stomach sections from kallistatin-overexpressing transgenic mice. Treatment
      with kallistatin recombinant protein decreased the LVD in the implanted gastric
      xenograft tumors of nude mice. To the best of our knowledge, the present study is
      the first to demonstrate that kallistatin possesses anti-lymphangiogenic activity
      in vitro and in vivo. Moreover, kallistatin inhibited proliferation and migration
      of hLECs by reducing the phosphorylation of ERK and Akt, respectively. These
      findings suggested that kallistatin may be a promising agent that could be used
      to suppress cancer metastasis by inhibiting both angiogenesis and
      lymphangiogenesis.

PMID- 28440476
TI  - Exploration of miR-1202 and miR-196a in human endometrial cancer based on high
      throughout gene screening analysis.
AB  - Altered microRNA (miRNA) expression has been reported to participate in the
      pathogenesis of several human diseases, and particularly cancer. The present
      study examined the involvement of various miRNAs in the pathophysiology of
      endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). We performed
      a high-throughput analysis of the miRNAs (miRNA microarray) found in samples of
      endometrial tissue obtained from 45 patients; among whom, 15 patients were
      diagnosed with EC, 15 patients were diagnosed with AEH, and the remainder were
      healthy donors. Next, we selected several miRNAs which exhibited at least a 2
      fold difference in expression with a P<0.05 to validate these changes in 3
      independent in vitro experiments that used real-time PCR analysis. Finally, miR
      1202 and miR-196a were selected as target molecules whose effects on cell
      apoptosis, cell cycle changes, cell migratory and invasive abilities were
      investigated using flow cytometric and Transwell assays, respectively, after pre
      treatment in vitro. After analyzing 125 miRNAs in a microarray assay, 6 miRNAs (3
      high and 3-low expression) were further evaluated via paired comparison in all 3
      groups. The validation test revealed a positive correlation between the
      microarray results and a high level of miR-1202 and a low level of miR-196a in
      the EC group, when compared with the AEH group. All of the data were normalized
      with data obtained from normal control donors. We found that either miR-1202
      silencing or miR-196a overexpression affected AN3CA and HEC-1-A cells by
      increasing their apoptosis level and inducing G1 phase arrest while decreasing
      their migratory and invasive abilities. Inhibitors of miR-1202 and mimics of miR
      196a may exert a protective effect, suggesting that miR-1202 and miR-196a may
      serve as biomarkers for evaluating the effectiveness of EC treatment.

PMID- 28440477
TI  - Synchronized dual pulse gastric electrical stimulation improves gastric emptying
      and activates enteric glial cells via upregulation of GFAP and S100B with
      different courses of subdiaphragmatic vagotomy in rats.
AB  - Previous research and clinical practice have indicated that damage to the vagal
      nerve may seriously affect gastrointestinal physiological movement behavior. The
      aim of the current study was to observe the change of gastric motility, as well
      as enteric glial cells (EGCs) in the stomach with different courses of vagal
      nerve transection in rats prior to and following synchronized dual pulse gastric
      electrical stimulation. The gastric emptying rates were measured to assess the
      gastric motility. The glial markers, containing calcium binding protein (S100B)
      and glial fibrillary acidic protein (GFAP), were detected by reverse
      transcription-quantitative polymerase chain reaction and double-labeling
      immunofluorescence analysis. Ultrastructural changes of EGCs were observed using
      transmission electron microscopy. Gastric emptying was delayed in the terminal
      vagotomy group, compared with the terminal control group. The effect of long-term
      synchronized dual pulse gastric electrical stimulation (SGES) was superior to
      short-term SGES in terminal groups. The expression levels of S100B/GFAP were
      markedly decreased in the terminal vagotomy group compared with the terminal
      control group. Following short-term or long-term SGES, S100B/GFAP gene and
      protein expression increased in terminal groups. However, long-term SGES was more
      effective than short-term SGES and the difference was statistically significant.
      Vagal nerve damage leads to gastric motility disorder and weakens the function of
      EGCs. Therefore, SGES may improve stomach movement behavior and restore the
      impaired EGCs. The underlying mechanism of the effect remains elusive, but maybe
      associated with activation of EGCs.

PMID- 28440478
TI  - Overexpression of secretory phospholipase A2-IIa supports cancer stem cell
      phenotype via HER/ERBB-elicited signaling in lung and prostate cancer cells.
AB  - Resistance to conventional chemotherapies remains a significant clinical
      challenge in treatment of cancer. The cancer stem cells (CSCs) have properties
      necessary for tumor initiation, resistance to therapy, and progression. HER/ERBB
      elicited signaling supports CSC properties. Our previous studies revealed that
      secretory phospholipase A2 group IIa (sPLA2-IIa) is overexpressed in both
      prostate and lung cancer cells, leading to an aberrant high level in the
      interstitial fluid, i.e., tumor microenvironment and blood. HER/ERBB-PI3K-Akt-NF
      kappaB signaling stimulates sPLA2-IIa overexpression, and in turn, sPLA2-IIa
      activates EGFR family receptors and HER/ERBB-elicited signaling and stimulates
      sPLA2-IIa overexpression in a positive feedback manner. The present study
      determined the molecular mechanisms of sPLA2-IIa in stimulating HER/ERBB-elicited
      signaling and supporting CSC properties. We found that sPLA2-IIa binds both EGFR
      and HER3 demonstrated by co-immunoprecipitation experiments and also indirectly
      interacts with HER2, suggesting that sPLA2-IIa functions as a ligand for both
      EGFR and HER3. Furthermore, both side population CSCs from non-small cell lung
      cancer (NSCLC) A549 and H1975 cells and ALDH1-high CSCs from castration-resistant
      prostate cancer (CRPC) 22Rv1 cells overexpress sPLA2-IIa and produce tumors when
      inoculated into subcutis of nude mice. Given an aberrant high level of sPLA2-IIa
      in the tumor microenvironment that should be much higher than that in the blood,
      our findings support the notion that sPLA2-IIa functions as a ligand for EGFR
      family receptors and supports CSC properties via HER/ERBB-elicited signaling,
      which may contribute to resistance to therapy and cancer progression.

PMID- 28440479
TI  - Wip1 regulates SKOV3 cell apoptosis through the p38 MAPK signaling pathway.
AB  - The aim of the present study was to explore the effect of silencing wild-type p53
      induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells.
      SKOV3 cells cultured in vitro were divided into three groups: untreated cells,
      cells transfected with control small interfering RNA (siRNA) and cells
      transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect
      cell apoptosis. Western blot analysis was performed to determine expression of
      tumor protein 53 (p53), cleaved caspase-3, caspase-3, BCL2 associated X (Bax),
      BCL2 apoptosis regulator (Bcl-2), p38 mitogen-activated protein kinase (p38 MAPK)
      and phosphorylated (p)-p38 MAPK. Reverse transcription-quantitative polymerase
      chain reaction was used to detect expression of p53, Bax, Bcl-2 and caspase-3
      mRNAs. Compared with control, apoptosis of SKOV3 cell was significantly increased
      following Wip1 siRNA silencing. Wip1 silencing also resulted in a significant
      increase of p53 and p-p38 MAPK expression, as well as increased cleaved caspase
      3/caspase-3 and Bax/Bcl-2 protein ratios. No significant differences were
      observed in apoptosis and apoptosis-related protein expression in the control
      siRNA transfected cells. The present study demonstrated that Wip1 silencing
      promotes apoptosis of human ovarian cancer SKOV3 cells by activation of the p38
      MAPK signaling pathways and through subsequent upregulation of p53, and cleaved
      caspase-3/caspase-3 and Bax/Bcl-2 protein ratios. Overall, the findings of the
      present study suggest that targeting Wip1 may be a potential therapeutic avenue
      for the treatment of human ovarian cancer in the future.

PMID- 28440480
TI  - Palmitate impairs angiogenesis via suppression of cathepsin activity.
AB  - Angiogenesis requires the interaction of multiple variable factors to promote
      endothelial cell adhesion, migration and survival. Palmitate, a free fatty acid,
      exhibits an anti-angiogenic effect via interference with endothelial cell
      function, whereas cysteine proteases are important in protein turnover and are
      termed positive modulators of neovascularization. However, the association
      between these two factors regarding the regulation of human endothelial cell
      function remains to be elucidated. By using cell counting kit-8, the Transwell
      method and an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis
      detection kit, the present study reported that high levels of palmitate result in
      a significant decrease in endothelial cell proliferation and invasion, and
      induced cell apoptosis; cathepsin L and S inhibitors may suppress palmitate
      induced apoptosis. Conversely, the results of the cathepsin L and S activity
      assay and reverse-transcription-quantitative polymerase chain reaction indicated
      that palmitate inhibited cathepsin-induced endothelial cell invasion, partially
      via suppressing the expression and activity of cathepsin L and S. The findings of
      the present study suggested that the potent anti-angiogenic properties of
      palmitate may be mediated by cysteine proteases.

PMID- 28440481
TI  - The specific killing effect of matrine on castration-resistant prostate cancer
      cells by targeting the Akt/FoxO3a signaling pathway.
AB  - Matrine, a Sophora alkaloid, exhibits antiproliferative and anti-carcinogenic
      activities through several mechanisms. In a previous study, we found that matrine
      could effectively inhibit the proliferation of castration-resistant prostate
      cancer (CRPC). In the present study, the effect of matrine and LY294002 on the
      expression of the Akt/FoxO3a signaling pathway was examined by western blot
      analyses and RT-PCR. We discovered that matrine significantly inhibited the
      proliferation of both prostate cancer cell line PC-3 and prostate epithelial cell
      line RWPE1, induced apoptosis and induced cell cycle arrest. In addition,
      LY294002 was found to enhance the effect of matrine. Furthermore, the effects of
      matrine on the inhibition of proliferation and the induction of cell cycle arrest
      and cell apoptosis were more effective on PC-3 than on RWPE1 cells. Compared to
      RWPE1 cells, matrine exerted a more powerful influence on PC-3 cells in
      increasing the expression of the relevant protein. Our data suggested that FoxO3a
      Bim and FoxO3a-P27 may mediate matrine-inhibited proliferation of CRPC cells by
      activating cell apoptosis and inducing cell cycle arrest. Matrine exhibited high
      selectivity in killing CRPC cells. Our findings demonstrated that matrine could
      be used in a potential therapeutic role in the management of CRPC in humans.

PMID- 28440482
TI  - KMUP-1 attenuates high glucose and transforming growth factor-beta1-induced pro
      fibrotic proteins in mesangial cells.
AB  - We have previously demonstrated that KMUP-1, a xanthine-based nitric oxide
      enhancer, attenuates diabetic glomerulosclerosis, while increasing renal
      endothelial nitric oxide synthase expression in rats. However, the anti-fibrotic
      mechanisms of KMUP-1 treatment in diabetic nephropathy in terms of cell biology
      and transforming growth factor-beta1 (TGF-beta1) remain unclear. Therefore, the
      present study involved investigating the effects of KMUP-1 on high glucose (HG)
      or TGF-beta1-induced pro-fibrotic proteins in mouse mesangial (MES13) cells, and
      the effects of KMUP-1 on streptozotocin (STZ)-induced diabetic rats. It was
      identified that KMUP-1 (10 uM) attenuated HG (30 mM)-induced cell hypertrophy
      while attenuating TGF-beta1 gene transcription and bioactivity in MES13 cells. In
      addition, KMUP-1 attenuated TGF-beta1 (5 ng/ml)-induced Smad2/3 phosphorylation
      while attenuating HG or TGF-beta1-induced collagen IV and fibronectin protein
      expression. Furthermore, KMUP-1 attenuated HG-decreased Suv39h1 and H3K9me3
      levels. Finally, KMUP-1 attenuated diabetes-induced collagen IV and fibronectin
      protein expression in STZ-diabetic rats at 8 weeks. In conclusion, KMUP-1
      attenuates HG and TGF-beta1-induced pro-fibrotic proteins in mesangial cells and
      attenuation of TGF-beta1-induced signaling and attenuation of HG-decreased
      Suv39h1 expression may be two of the anti-fibrotic mechanisms of KMUP-1.

PMID- 28440483
TI  - Human osteopontin: Potential clinical applications in cancer (Review).
AB  - Human osteopontin (OPN) is a glycosylated phosphoprotein which is expressed in a
      variety of tissues in the body. In recent years, accumulating evidence has
      indicated that the aberrant expression of OPN is closely associated with
      tumourigensis, progression and most prominently with metastasis in several tumour
      types. In this review, we present the current knowledge on the expression
      profiles of OPN and its main splice variants in human cancers, as well as the
      potential implications in patient outcome. We also discuss its putative clinical
      application as a cancer biomarker and as a therapeutic target.

PMID- 28440484
TI  - Expression of programmed cell death1 in T follicular helper cells is regulated by
      prostaglandin E2 secreted by HBV-infected HepG2.2.1.5 cells.
AB  - The present study aimed to investigate the distribution of T follicular helper
      (Tfh)-cell subsets in patients with hepatitis B virus (HBV) and determine the
      underlying mechanism of HBV regulation of Tfh cells. The frequency of peripheral
      blood Tfh subsets was analyzed using flow cytometry. The expression level of
      programmed cell death-1 (PD-1) and prostaglandin E2 (PGE2) was quantified using
      reverse transcription-quantitative polymerase chain reaction and western
      blotting. The PGE2 level in culture supernatant was detected using enzyme-linked
      immunosorbent assay. A Transwell chamber was used to co-culture Tfh cells with
      HepG2 and HepG2.2.1.5. The percentage of inducible T-cell costimulator (ICOS)+
      and total Tfh cells was high at the immune activation (IA) group; however, it was
      reduced in the immune tolerance (IT), responders with HBsAg seroconversion (RP)
      and healthy control (HC) groups. The percentage of PD-1+ Tfh cells was
      significantly higher in IA and IT compared with RP and HC. The ratio of PD
      1+/total Tfh cells was positively correlated with the load of HBV DNA; therefore,
      this ratio may act as an indicator for HBV replication. The expression level of
      PD-1 in Tfh cells was higher in the HepG2.2.1.5 co-cultured group compared with
      the HepG2 group, this may be due to the high PGE2 expression level in HBV
      infected HepG2.2.1.5 cells. The findings of the present study revealed an
      imbalanced distribution of PD-1+ Tfh cells in patients with HBV at different
      immune phases. Additionally, HBV may upregulate the expression of PD-1 in Tfh
      cells by promoting HepG2.2.1.5 to secret PGE2. Identifying the effect of HBV on
      Tfh-cell subsets is crucial for improving immuno-based therapy for HBV.

PMID- 28440485
TI  - Sclareol inhibits cell proliferation and sensitizes cells to the
      antiproliferative effect of bortezomib via upregulating the tumor suppressor
      caveolin-1 in cervical cancer cells.
AB  - The anticancer effect of sclareol has long been reported, however, the exact
      mechanisms underlying the antitumorigenic effect of sclareol in cervical
      carcinoma remain to be fully elucidated. The present study analyzed cell
      proliferation and cell apoptosis by MTT and FITC-Annexin V assays. The protein
      levels of caveolin-1 (Cav-1) and copper-zinc superoxide dismutase (SOD)1 were
      determined by western blotting, and the interaction of Cav1 and HSC70 was
      investigated by co-immunoprecipitation experiments. The present study found that
      sclareol inhibited cell proliferation and induced apoptosis in HeLa cells. Two
      cancer-associated proteins, Cav1 and SOD1 were identified as potential targets of
      sclareol in HeLa cells. The expression of Cav1 increased when the cells were
      treated with sclareol, and the protein level of SOD1 was negatively correlated
      with Cav1. The overexpression of Cav1 enhanced the sensitivity of the HeLa cells
      to sclareol treatment and downregulated the protein level of SOD1, which
      exhibited potential associations between Cav1 and SOD1. In addition, sclareol
      significantly sensitized several cancer cells to the anticancer effect of
      bortezomib by targeting Cav1 and SOD1. Taken together, the results of the present
      study demonstrated that sclareol inhibited tumor cell growth through the
      upregulation of Cav1, and provides a potential therapeutic target for human
      cancer.

PMID- 28440486
TI  - Synergistic antitumor effects of CDK inhibitor SNS-032 and an oncolytic
      adenovirus co-expressing TRAIL and Smac in pancreatic cancer.
AB  - Gene therapy using oncolytic adenoviruses is a novel approach for human cancer
      therapeutics. The current study aimed to investigate whether the combined use of
      an adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) and second mitochondria-derived activator of caspase (Smac) upon caspase
      activation (ZD55-TRAIL-IETD-Smac) and cyclin-dependent kinase (CDK) inhibitor SNS
      032 will synergistically reinforce their anti-pancreatic cancer activities. The
      experiments in vitro demonstrated that SNS-032 enhances ZD55-TRAIL-IETD-Smac
      induced apoptosis and causes marked pancreatic cancer cell death. Western blot
      assays suggested that the SNS-032 intensified ZD55-TRAIL-IETD-Smac-induced
      apoptosis of pancreatic cancer cells by affecting anti-apoptotic signaling
      elements, including CDK-2, CDK-9, Mcl-1 and XIAP. Additionally, animal
      experiments further confirmed that the combination of SNS-032 and ZD55-TRAIL-IETD
      Smac significantly inhibited the growth of BxPC-3 pancreatic tumor xenografts. In
      conclusion, the present study demonstrated that SNS-032 sensitizes human
      pancreatic cancer cells to ZD55-TRAIL-IETD-Smac-induced cell death in vitro and
      in vivo. These findings indicate that combined treatment with SNS-032 and ZD55
      TRAIL-IETD-Smac could represent a rational approach for anti-pancreatic cancer
      therapy.

PMID- 28440487
TI  - Interaction between interleukin-6 and angiotensin II receptor 1 in the
      hypothalamic paraventricular nucleus contributes to progression of heart failure.
AB  - The association between interleukin-6 (IL-6) and angiotensin II receptor 1 (AT1
      R) in modulating the progression of heart failure (HF) remains to be fully
      elucidated. The aim of the present study was to investigate the mechanism of IL-6
      and AT1-R in a model of HF induced by surgery. Male Sprague-Dawley rats were
      randomly divided into five groups, including sham surgery and vehicle groups. The
      animals were treated for 4 weeks via paraventricular nucleus infusion with either
      vehicle, losartan (LOS; 200 ug/day), IL-6 (1 ug/day) or LOS and IL-6 together
      (LOS+IL-6). The rats with HF had higher levels of IL-6, corticotropin-releasing
      hormone (CRH) and norepinephrine (NE), and a lower level of neuronal nitric oxide
      synthase (nNOS), compared with the rats in the sham surgery group. Treatment with
      LOS attenuated the decrease in nNOS and the increases in IL-6, CRH and NE;
      whereas treatment with IL-6 facilitated the lower expression of nNOS and higher
      expression levels of IL-6, CRH and NE. No differences in the expression levels of
      nNOS, CRH or NE were found between the LOS group and LOS+IL-6 group. The results
      of the study demonstrated that IL-6 contributed to the progression of HF via the
      AT1-R pathway.

PMID- 28440488
TI  - Dipeptidyl peptidase-4 inhibitor sitagliptin prevents high glucose-induced
      apoptosis via activation of AMP-activated protein kinase in endothelial cells.
AB  - Diabetes mellitus (DM), which is a chronic metabolic disorder, is the primary
      risk factor of life-threatening vascular complications. Endothelial apoptosis is
      important in the development of the initial vascular lesion preceding the
      diabetic disease. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor and
      extensively used in the clinical treatment of DM. DPP-4 inhibitors have been
      demonstrated to be beneficial in the improvement of endothelial homeostasis,
      however the molecular mechanism by which they exhibit these effects remains to be
      elucidated. The effect of sitagliptin on endothelial apoptosis was examined in
      cultured human umbilical vein endothelial cells (HUVECs) incubated with high
      glucose (HG). The present study demonstrated that treatment of HUVECs with HG
      increased reactive oxygen species (ROS) production, stimulated mitochondrial
      depolarization and resulted in cell apoptosis. Pretreatment of HUVECs with
      sitagliptin significantly prevented HG-induced endothelial apoptosis. It was
      further demonstrated that sitagliptin effectively inhibited ROS generation and
      mitochondrial membrane potential collapse. Similarly, adenosine monophosphate
      activated protein kinase (AMPK) activation by sitagliptin protected against HG
      induced ROS production, mitochondrial membrane potential collapse and endothelial
      cell apoptosis, as detected via western blotting and flow cytometry analysis. The
      present study therefore revealed a novel mechanism of sitagliptin-mediated AMPK
      activation in preventing endothelial apoptosis and indicated the therapeutic
      potential of sitagliptin in vascular complications associated with endothelial
      apoptosis.

PMID- 28440489
TI  - Genome-wide DNA methylation sequencing reveals miR-663a is a novel epimutation
      candidate in CIMP-high endometrial cancer.
AB  - Aberrant DNA methylation is widely observed in many cancers. Concurrent DNA
      methylation of multiple genes occurs in endometrial cancer and is referred to as
      the CpG island methylator phenotype (CIMP). However, the features and causes of
      CIMP-positive endometrial cancer are not well understood. To investigate DNA
      methylation features characteristic to CIMP-positive endometrial cancer, we first
      classified samples from 25 patients with endometrial cancer based on the
      methylation status of three genes, i.e. MLH1, CDH1 (E-cadherin) and APC: CIMP
      high (CIMP-H, 2/25, 8.0%), CIMP-low (CIMP-L, 7/25, 28.0%) and CIMP-negative
      (CIMP(-), 16/25, 64.0%). We then selected two samples each from CIMP-H and CIMP(
      ) classes, and analyzed DNA methylation status of both normal (peripheral blood
      cells: PBCs) and cancer tissues by genome-wide, targeted bisulfite sequencing.
      Genomes of the CIMP-H cancer tissues were significantly hypermethylated compared
      to those of the CIMP(-). Surprisingly, in normal tissues of the CIMP-H patients,
      promoter region of the miR-663a locus is hypermethylated relative to CIMP(-)
      samples. Consistent with this finding, miR-663a expression was lower in the CIMP
      H PBCs than in the CIMP(-) PBCs. The same region of the miR663a locus is found to
      be highly methylated in cancer tissues of both CIMP-H and CIMP(-) cases. This is
      the first report showing that aberrant DNA methylation of the miR-663a promoter
      can occur in normal tissue of the cancer patients, suggesting a possible link
      between this epigenetic abnormality and endometrial cancer. This raises the
      possibility that the hypermethylation of the miR-663a promoter represents an
      epimutation associated with the CIMP-H endometrial cancers. Based on these
      findings, relationship of the aberrant DNA methylation and CIMP-H phenotype is
      discussed.

PMID- 28440490
TI  - MicroRNA-15a inhibition protects against hypoxia/reoxygenation-induced apoptosis
      of cardiomyocytes by targeting mothers against decapentaplegic homolog 7.
AB  - Myocardial ischemia/reperfusion (I/R) injury is a major pathological process in
      coronary heart disease and cardiac surgery, and is associated with aberrant
      microRNA (miR) expression. Previous studies have demonstrated that inhibition of
      miR-15a expression may ameliorate I/R-induced myocardial injury. In the present
      study, the potential role and underlying mechanism of miR-15a in
      hypoxia/reoxygenation-induced apoptosis of cardiomyocytes was investigated.
      Myocardial I/R was simulated in cultured H9c2 cells by 24 h hypoxia followed by
      24 h reoxygenation. Using recombinant lentivirus vectors, the inhibition of miR
      15a was indicated to significantly reduce cardiomyocyte apoptosis and release of
      lactate dehydrogenase and malondialdehyde. Conversely, upregulated miR-15a
      expression was pro-apoptotic. Mothers against decapentaplegic homolog 7 (SMAD7)
      was identified by bioinformatics analysis as a potential target of miR-15a.
      Luciferase reporter assays and western blotting for endogenous SMAD7 protein
      indicated that miR-15a inhibited SMAD7 expression via its 3'-untranslated region.
      Nuclear levels of nuclear factor-kappaB (NF-kappaB) p65 were increased by miR-15a
      expression and decreased by miR-15a inhibition, which is consistent with the
      possibility that the inhibition of SMAD7 by miR-15a results in NF-kappaB
      activation. These findings suggested that the therapeutic effects of miR-15a
      inhibition on I/R injury may potentially be explained by its ability to release
      SMAD-7-dependent NF-kappaB inhibition. This may provide evidence for miR-15a as a
      potential therapeutic target for the treatment of cardiac I/R injury.

PMID- 28440491
TI  - TXNIP overexpression suppresses proliferation and induces apoptosis in SMMC7221
      cells through ROS generation and MAPK pathway activation.
AB  - Thioredoxin binding protein (thioredoxin-interacting protein, TXNIP), known as
      vitamin D3 increase protein 1, has been identified as a tumor suppressor in
      various cancers such as pancreatic, breast, lung and thyroid cancer. However, the
      role of TXNIP in hepatocellular carcinoma cell proliferation and apoptosis
      remains unknown. In this study, we first used qRT-PCR, western blotting and
      immunohistochemistry to compare the expression of TXNIP between hepatocellular
      carcinoma tissues and tumor-adjacent normal liver tissues. In vitro, we explored
      the role of TXNIP in hepatocellular carcinoma progression via transfection of the
      pcDNA-3.1-TXNIP plasmid into SMMC7221 cells. Our results showed that the
      expression of TXNIP was significantly decreased in hepatocellular carcinoma
      tissues. Moreover, TXNIP over-expression inhibited hepatocellular carcinoma cell
      proliferation and induced apoptosis by triggering mitochondrial-mediated ROS
      generation and activating MAPK pathways. This study provides insight into the
      molecular mechanisms of TXNIP overexpression in liver cancer cell survival and
      apoptosis and indicated that TXNIP may be a novel promising agent for liver
      cancer treatment.

PMID- 28440492
TI  - AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier.
AB  - AXL, a receptor tyrosine kinase implicated in cell survival, proliferation, and
      migration, is also associated with acquired resistance to epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor therapy. However, its prognostic
      significance in lung adenocarcinoma (AD) remains unclear. We therefore evaluated
      the prognostic significance of the expression of AXL and/or its ligand, growth
      arrest-specific 6 (GAS6), in completely resected lung AD. We evaluated the
      relationship between AXL, GAS6, and vimentin expression, as determined by
      immunohistochemistry (IHC) analysis, with overall survival and disease-free
      survival in 113 patients with stages I-III lung AD. Protein expression was also
      assayed using western blot analysis in 10 lung AD cell lines. AXL-positive
      (AXL+), GAS6-positive (GAS6+), or AXL+/GAS6+ staining was significantly
      associated with vimentin-positive (vimentin+) expression. AXL+/GAS6+ and
      vimentin+ showed a negative tendency toward an association with EGFR mutation.
      AXL+, GAS6+, or AXL+/GAS6+ status significantly correlated with poor overall
      survival. In stage I cases, AXL+/GAS6+ status significantly correlated with poor
      overall survival and disease-free survival, especially in cases with wild-type
      EGFR. In multivariate analysis, AXL/GAS6 classifications in stage I as well as in
      stages I-III lung AD were found to be independent factors for poor patient
      outcomes. Unlike lung AD cell lines with mutant EGFR, almost all cells with wild
      type EGFR showed AXL and vimentin co-expression as determined by western
      blotting. AXL+ and GAS6+ expression is relevant to a poor prognosis in resected
      lung AD patients at stage I. AXL/GAS6 might serve as crucial predictive and
      prognostic biomarkers and targets to identify individuals at high risk of post
      operative death.

PMID- 28440494
TI  - Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer.
AB  - Tumor-associated macrophages of the M2 phenotype promote tumor proliferation and
      are associated with a poor prognosis in patients with various malignancies,
      including gastric cancer with peritoneal dissemination. The present study
      assessed whether paclitaxel (PTX) suppresses M2 macrophages, by acting as a Toll
      like receptor 4 (TLR4) agonist. Macrophages derived from the THP-1 monocytic cell
      line and peripheral blood mononuclear cell (PBMC)-derived macrophages were
      cultured with gastric cancer cells in medium containing PTX, at a concentration
      that did not affect cell proliferation. The effects of PTX on macrophage
      expression of CD204, a marker of M2 macrophages and NOS2, a marker of M1
      macrophages, was evaluated by western blotting. The ability of PTX to stimulate
      intranuclear translocation of NF-kappaB was determined by evaluating the
      expression of the p65 subunit of NF-kappaB. In THP-1 macrophages, low-dose PTX (1
      and 5 nM) inhibited the expression of CD204, enhanced the expression of NOS2, and
      significantly suppressed the phosphorylation of Stat3, which is essential for the
      M2 phenotype. Low-dose PTX also inhibited CD204 expression in primary macrophages
      derived from PBMCs. PTX treatment of THP-1 macrophages for 1 h induced marked
      intranuclear translocation of NF-kappaB p65. Low-dose PTX inhibited the M2
      phenotype and induced the M1 phenotype via TLR4 signaling, suggesting that low
      dose PTX can alter the macrophage phenotype, whereas clinical doses can kill
      cancer cells. These results suggest that the anticancer effects of PTX are due
      both to its cytotoxic and immunomodulatory activities.

PMID- 28440493
TI  - The extracellular signal-regulated kinase 1/2 pathway in neurological diseases: A
      potential therapeutic target (Review).
AB  - Signaling pathways are critical modulators of a variety of physiological and
      pathological processes, and the abnormal activation of some signaling pathways
      can contribute to disease progression in various conditions. As a result,
      signaling pathways have emerged as an important tool through which the occurrence
      and development of diseases can be studied, which may then lead to the
      development of novel drugs. Accumulating evidence supports a key role for
      extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the embryonic
      development of the central nervous system (CNS) and in the regulation of adult
      brain function. ERK1/2, one of the most well characterized members of the mitogen
      activated protein kinase family, regulates a range of processes, from metabolism,
      motility and inflammation, to cell death and survival. In the nervous system,
      ERK1/2 regulates synaptic plasticity, brain development and repair as well as
      memory formation. ERK1/2 is also a potent effector of neuronal death and
      neuroinflammation in many CNS diseases. This review summarizes recent findings in
      neurobiological ERK1/2 research, with a special emphasis on findings that clarify
      our understanding of the processes that regulate the plethora of isoform-specific
      ERK functions under physiological and pathological conditions. Finally, we
      suggest some potential therapeutic strategies associated with agents acting on
      the ERK1/2 signaling to prevent or treat neurological diseases.

PMID- 28440495
TI  - Relationship between epigenetic changes in Wnt antagonists and acute leukemia.
AB  - The present study was designed to investigate the relationship among epigenetic
      changes in Wnt antagonists, histone H4K20me1 and the expression of tumor
      suppressor genes in acute leukemia (AL) to better understand the pathogenesis of
      leukemia. Quantitative reverse transcription polymerase chain reaction (qRT-PCR)
      was performed to detect messenger RNA (mRNA) expression levels of Wnt antagonists
      (Wnt5a, HDPR1, DKK1 and DKK3) in patients with AL and in normal controls;
      pyrophosphate sequencing was performed to detect the methylation status of the
      Wnt5a promoter; and western blotting was performed to detect the overall
      expression levels of Wnt5a protein and histone H4K20me1 in patients with acute
      myeloid leukemia (AML) and in normal controls. The relationship between Wnt5a
      protein expression and histone H4K20me1 was analyzed. Chromatin
      immunoprecipitation-qPCR (ChIP-qPCR) was performed to investigate the recruitment
      of H4K20me1 and SET8 to the Wnt5a promoter and coding regions. Our results
      demonstrated that the expression levels of Wnt antagonists were generally low in
      AML, but showed differential expression in acute lymphocytic leukemia (ALL). In
      most cases of AML, methylation of the Wnt5a promoter was observed and Wnt5a
      protein expression was low. In some cases of AML, the overall level of H4K20me1
      protein was higher than that in normal controls. In addition, Wnt5a expression
      was positively correlated with H4K20me1 expression and was unrelated to the
      methylation status of its promoter. Moreover, H4K20me1 and SET8 were enriched in
      the Wnt5a promoter region and coding region. By contrast, Wnt5a expression was
      unrelated to H4K20me1 expression in normal controls. Moreover, we observed that
      the methylation of Wnt antagonists was often found in patients with AL,
      particularly those with AML, whereas the extent of methylation was variable in
      ALL patients. Wnt5a expression was positively correlated with the enrichment of
      H4K20me1 and SET8 at the Wnt5a promoter and coding regions. H4K20me1 increased
      Wnt5a expression by promoting transcription initiation and elongation.

PMID- 28440496
TI  - PU.1 serves a critical role in the innate defense against Aspergillus fumigatus
      via dendritic cell-associated C-type lectin receptor-1 and toll-like receptors-2
      and 4 in THP-1-derived macrophages.
AB  - Aspergillus fumigatus (A. fumigatus) is one of the most common fungal pathogens
      of invasive pulmonary aspergillosis (IPA), which may be life threatening in
      immunocompromised individuals. The dendritic cell-associated C-type lectin
      receptor (Dectin-1), toll-like receptor (TLR)-2 and TLR-4 are major pattern
      recognition receptors in alveolar macrophages that recognize A. fumigatus
      components. The PU.1 transcription factor is known to be important for the
      transcriptional control of these three receptors in mature macrophages. The
      present study investigated whether alterations of PU.1 expression may affect the
      innate defense against A. fumigatus in the human monocyte THP-1 cell line. THP-1
      derived macrophages were transduced with PU.1 adenoviral vectors and transfected
      with PU.1 small interfering RNA, and the mRNA and protein expression levels of
      Dectin-1, TLR-2 and TLR-4 were measured. In addition, the levels of tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta were ascertained, and
      fungal phagocytosis and killing were assessed. The results demonstrated that
      overexpression of PU.1 by recombinant adenoviral vectors resulted in a
      significant upregulation of Dectin-1, TLR-2 and TLR-4 at the transcriptional and
      translational levels. In response to A. fumigatus stimulation, PU.1
      overexpression increased TNF-alpha and IL-1beta production. In addition, Dectin
      1, TLR-2 and TLR-4 upregulation may have enhanced the phagocytosis and killing
      ability of THP-1-derived macrophages. As expected, silencing of PU.1 led to
      downregulation of Dectin-1, TLR-2, TLR-4 and the expression of pro-inflammatory
      cytokines, as well as decreased phagocytosis and the killing ability of THP1
      derived macrophages. In conclusion, the results indicate that PU.1 may be a
      critical factor for the innate defense against A. fumigatus, and may therefore be
      a potential target for the prophylaxis and treatment of IPA.

PMID- 28440497
TI  - miR-27a promotes proliferation, migration, and invasion of colorectal cancer by
      targeting FAM172A and acts as a diagnostic and prognostic biomarker.
AB  - Accumulating evidence shows that mircroRNAs (miRNAs) play a crucial role in the
      development of colorectal cancer. In our previous study, FAM172A was demonstrated
      to be a novel tumor suppressor gene in CRC. Therefore, the aim of the present
      study was to identify whether the miR-27a could be a diagnostic and prognostic
      marker and the regulatory relationships between miR-27a and FAM172A. We
      demonstrated high levels of miR-27a expression in tissues of patients with CRC as
      well as in CRC cell lines. There was a positive correlation between the levels of
      miR-27a and the poor overall survival of patients with CRC. Furthermore, elevated
      levels of miR-27a expression were associated with TNM stage and distant
      metastasis. Increased expression or inhibition of miR-27a promoted or inhibited
      the metastasis of CRC cell lines, respectively. Moreover, we showed that miR-27a
      directly targets the 3'-untranslated region of FAM172A mRNA by using a dual
      luciferase assay. Increased or decreased expression of FAM172A expression was
      observed when miR-27a expression was inhibited or elevated in the CRC cells,
      respectively. In summary, our study showed that miR-27a expression is a
      diagnostic and prognostic marker and correlates with overall survival of patients
      with CRC. Therefore, it may be a therapeutic approach for preventing metastasis
      of CRC to inhibit expression of miR-27a or increase expression of FAM172A.

PMID- 28440498
TI  - Differentiation of human induced pluripotent stem cells in William's E initiation
      medium supplemented with 3-bromopyruvate and 2-deoxy-d-glucose.
AB  - Hepatocyte selection medium (HSM) is deprived of glucose and supplemented with
      galactose, and is based on Leibovitz's-15 (L15) medium. HSM may promote the
      differentiation of human induced pluripotent stem (iPS) cells towards hepatocyte
      lineage. These culture conditions result in increased expression of galactokinase
      (GALK)-1 and GALK2. However, iPS cells do not survive in HSM. Two potential
      alternatives to glucose deprivation are treatment with 3-bromopyruvate (3BP), an
      analogue of pyruvate, and 2-deoxy-d-glucose (2DG), an analogue of glucose. The
      promoters of GALK1 and GALK2 were subcloned using the pMetLuc2 reporter plasmid
      to make pMetLuc2/GALK1 and pMetLuc2/GALK2, respectively. 201B7 human iPS cells
      were transfected with the reporter plasmids, cultured in HSM and analyzed by
      luciferase assay. Furthermore, 201B7 cells were cultured in L15, William's E (WE)
      or Dulbecco's modified Eagle's medium/nutrient mixture F-12 Ham (DF12)
      supplemented with 3BP, 2DG or a combination of the two, for 15 days, and
      subjected to reverse transcription-quantitative polymerase chain reaction to
      measure the levels of alpha-fetoprotein (AFP) mRNA expression. Metridia
      luciferase activity was significantly higher in cells cultured in HSM compared
      with those in ReproFF medium (P<0.05). 3BP and 2DG treatment, alone or in
      combination, decreased AFP expression levels in cells cultured in L15 and DF12.
      The combination of 3BP+2DG increased the expression levels of AFP in WE. Without
      3BP or 2DG, AFP expression was higher in L15 compared with WE or DF12. The
      promoters of GALK1 and GALK2 were activated in 201B7 cells cultured in HSM,
      enabling survival using galactose as an energy source. 3BP and 2DG
      supplementation in WE medium may promote the differentiation of iPS cells to the
      hepatocyte lineage.

PMID- 28440499
TI  - Effects of tanshinone IIA on the regulation of renal proximal tubular fibrosis.
AB  - The development of diabetes mellitus, along with its complications, is a chronic
      inflammatory response process. Chronic kidney diseases are characterized by renal
      fibrosis, and fibrosis is an important pathway for end-stage renal failure.
      According to previous studies, high glucose (HG) has been demonstrated to be the
      most important fibrogenesis-inducing agent. Tanshinone IIA is one of the main
      components isolated from Danshen (Salvia miltiorrhiza). Although tanshinone IIA
      has been widely used for the treatment of cardiovascular diseases, the possible
      role of tanshinone IIA in fibrosis regulation remains to be elucidated and
      requires investigation. In the present study, renal proximal tubular epithelial
      cells (HK-2) were treated with HG (30 mM glucose) to determine whether tanshinone
      IIA (1, 10 and 50 uM) had an effect on the regulation of renal cellular fibrosis.
      The results demonstrated that 50 uM tanshinone IIA may exert optimal inhibitory
      effects on HG-induced Snail, fibronectin, vimentin and alpha-smooth muscle actin
      (alpha-SMA) expression in HK-2 cells after 48 h. Tanshinone IIA also reversed HG
      induced morphological alterations in HK-2 cells and inhibited an HG-induced
      increase in fibronectin and alpha-SMA mRNA and protein and an HG-induced decrease
      in E-cadherin. Furthermore, tanshinone IIA suppressed an HG-induced increase in
      Snail, which is a transcription factor that can suppress E-cadherin expression. E
      cadherin is a major component of adherens junctions and a characteristic of
      epithelial integrity. Tanshinone IIA reversed HG-induced increase in alpha-SMA
      and decrease in E-cadherin. These data suggest that tanshinone IIA has the
      potential to inhibit HG-induced renal tubular epithelial cell fibrosis possibly
      through the epithelial-myofibroblast transdifferentiation pathway. Therefore,
      tanshinone IIA may be considered a renoprotective agent for the treatment of
      renal fibrosis.

PMID- 28440500
TI  - Indirect effects of X-irradiation on proliferation and osteogenic potential of
      bone marrow mesenchymal stem cells in a local irradiated rat model.
AB  - Cancer survivors after radiotherapy may suffer a variety of bone-related adverse
      side effects, including radioactive osteoporosis and fractures. Localized
      irradiation is a common treatment modality for malignancies. Recently, a series
      of reactions and injuries called indirect effects (remote changes in bone when
      other parts of the body are irradiated) have been reported on the indirect
      irradiated area of bone tissue after radiotherapy. To address this issue, we
      developed a rat localized irradiation model. Rats were irradiated with a single
      dose of X-rays to the left hind limbs, and bone marrow mesenchymal stem cells
      (BMMSCs) were isolated from bone marrow of the left (direct irradiated) and right
      (indirect irradiated) hind limbs 3, 7 and 14 days after irradiation, and assayed
      for the proliferation ability and osteogenic potential by alkaline phosphatase
      (ALP) activity, mineralization assay, RT-PCR and western blot analysis. The
      results showed that there were significant morphology changes in the BMMSCs from
      direct and indirect irradiated bone tissue with bigger cell bodies and increased
      granules. The proliferation of BMMSCs decreased both in the direct irradiated and
      non-irradiated bone tissue. The ALP expression and activities of BMMSCs from
      direct irradiated bone was consistently defected following a transient
      enhancement, the mRNA levels of RUNX2 and OCN, the protein expression of RUNX2,
      and the mineralization ability also showed the same trend. Simultaneously, in
      indirect irradiated group, the osteogenic potential indicators of BMMSCs
      decreased in the early stage of post-irradiation and were still impaired 14 days
      after irradiation. Our data demonstrate that localized irradiation may have both
      direct and indirect adverse effects on BMMSCs' proliferation and osteogenic
      potential into osteoblast, which may be the mechanism of radiation-induced
      abscopal impairment to the skeleton in the cancer radiotherapy-induced bone loss.

PMID- 28440501
TI  - Transfer of CD11c+ lamina propria mononuclear phagocytes from post-infectious
      irritable bowel syndrome causes mucosal barrier dysfunction and visceral
      hypersensitivity in recipient mice.
AB  - The role of low-grade inflammation in the development of post-infectious
      irritable bowel syndrome (PI-IBS) has attracted increasing attention. Abnormal
      CD11c+ mononuclear phagocytes, such as dendritic cells (DCs), macrophages, and
      monocytes, are involved in the disruption of immune tolerance in organisms, which
      can lead to the development of chronic inflammatory diseases. The present study
      tested the hypothesis that CD11c+ lamina propria mononuclear phagocytes (CD11c+
      LPMPs) contribute to increased mucosal permeability and visceral hypersensitivity
      in a PI-IBS mouse model. CD11c+ LPMPs were isolated and purified via the
      digestion of intestinal tissues and magnetic-activated cell sorting. We detected
      increased mucosal permeability, visceral hypersensitivity and intestinal
      inflammation during both the acute and chronic stages of Trichinella infection.
      Following the transfer of CD11c+ LPMPs from PI-IBS mice into normal mice, low
      grade inflammation was detected, as demonstrated by increased IL-4 expression in
      the ileum, as well as enhanced mucosal permeability, as indicated by decreased
      transepithelial electrical resistance and the pre-sence of ultrastructural
      alterations. More importantly, the mice that underwent adoptive transfer of
      CD11c+ LPMPs from the PI-IBS mice also exhibited increased abdominal withdrawal
      reflex scores and a decreased threshold. Our data demonstrated that the CD11c+
      LPMPs from this PI-IBS mouse model were not only able to transfer enteric
      inflammation to the normal mice but also caused abnormal intestinal function,
      characterized by epithelial barrier disruption and visceral hyperalgesia.

PMID- 28440502
TI  - Marine actinomycete crude extracts with potent TRAIL-resistance overcoming
      activity against breast cancer cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      anticancer agent, as it can kill tumor cells selectively. In our search of
      bioactive natural products to overcome TRAIL-resistance, we isolated 47
      actinomycete strains from different sediments and seawater samples collected from
      the Red Sea coast in Egypt and found four crude extracts (EGY1, EGY3, EGY24 and
      EGY34) displaying TRAIL sensitizing activity in the resistant breast cancer cell
      line MDA-MB-231. None of these crude extracts exhibited cytotoxic effect on
      normal mouse embryonic fibroblasts (MEF), with the exception of EGY34. Analysis
      of the signaling pathways underlying the sensitization of MDA-MB-231 cells to
      TRAIL-induced apoptosis, by western blotting, revealed that all crude extracts
      facilitated initiator caspase-8/-10 activation upon TRAIL stimulation, but that
      in addition, EGY3 and EGY34, alone, induced strong ER-stress activation, with the
      appearance of BiP in the cytosolic extracts. Our results pave the way to the
      discovery and the development of marine-derived drugs for cancer therapy.

PMID- 28440503
TI  - CD24 expression is a marker for predicting clinical outcome and regulates the
      epithelial-mesenchymal transition in ovarian cancer via both the Akt and ERK
      pathways.
AB  - The degree of peritoneal dissemination and chemotherapy-resistant tumors is
      related to the prognosis in patients with advanced-stage ovarian cancer. The
      epithelial-mesenchymal-transition (EMT) is a multifaceted pathological program
      that endows cancer cells with the ability to invade and disseminate. CD24 is
      frequently overexpressed in various human cancers and is correlated with a poor
      prognosis. We herein examined the functions of CD24 in human ovarian cancer cell
      lines and evaluated how it contributes to the molecular mechanism underlying the
      regeneration of cancer stem-like cells (CSCs) through the EMT mechanism in
      ovarian carcinoma. We demonstrated that CD24 was expressed in 70.1% of primary
      ovarian carcinoma tissues, which were obtained from 174 patients, and that the
      expression of CD24 was an independent predictor of survival in patients with
      ovarian cancer. The expression of CD24 has been found to be correlated with the
      FIGO stage, presence of peritoneal and lymph node metastasis. CD24 induces the
      EMT phenomenon, which is involved in cell invasion, the highly proliferative
      phenotype, colony formation and which is associated with cisplatin resistance and
      the properties of CSCs, via the activation of PI3K/Akt, NF-kappaB and ERK in Caov
      3 cisplatin-resistant cell lines. CD24-positive ovarian carcinomas have been
      shown to have a greater potential for intra-abdominal tumor cell dissemination in
      in vivo models. Our findings suggest that CD24 induced the EMT phenomenon in
      ovarian cancer, and that CD24 amplified cell growth-related intracellular
      signaling via the PI3K/Akt and MAPK pathways by affecting the EMT signal
      pathways. We believe that CD24 is a key molecule of metastatic progression in the
      EMT phenomenon and a promising therapeutic target for advanced ovarian cancer.

PMID- 28440504
TI  - AdipoR1-mediated miR-3908 inhibits glioblastoma tumorigenicity through
      downregulation of STAT2 associated with the AMPK/SIRT1 pathway.
AB  - A prospective method of treatment for cancer is to inhibit oncogene signaling
      pathways with microRNA (miRNA or miR). In the present study, whether the
      expression of STAT2, AdipoR1/AMPK/SIRT1 pathway of glioma is regulated by miR
      3908 was explored. To confirm whether the predicted miR-3908 is matched with
      STAT2 and AdipoR1, 3'UTR luciferase activity of STAT2 and AdipoR1 was assessed.
      In the presence of the mimics or inhibitors of miR-3908, cell function of glioma
      cells, such as proliferation, growth, migration, invasion and apoptosis were
      analyzed. The expression of AdipoR1 and its downstream AMPK/SIRT1 pathway
      proteins or STAT2 were examined. Luciferase reporter analysis showed that miR
      3908 directly target STAT2 and AdipoR1. miR-3908 suppressed expression of STAT2
      or AdipoR1 and downregulated AdipoR1 pathway genes, including AMPK, p-AMPK and
      SIRT1. miR-3908 inhibited tumorigenicity, migration, growth and invasion in
      glioma cell lines U251 and U87 as well as increased apoptosis of these cells. The
      pathways related to tumorigenicity and tumor progression, STAT2 and
      AdipoR1/AMPK/SIRT1 could be restrained by miR-3908. In conclusion, restoration of
      miR-3908 expression induced suppression of cancer progression and glioblastoma
      tumorigenicity. The present study discovered novel tumorigenesis associated with
      miR-3908, which may represent a new target in treatment for glioblastoma.

PMID- 28440505
TI  - Detection of fetal epigenetic biomarkers through genome-wide DNA methylation
      study for non-invasive prenatal diagnosis.
AB  - The discovery of cell-free DNA fetal (cff DNA) in maternal plasma during
      pregnancy provides a novel perspective for the development of non-invasive
      prenatal diagnosis (NIPD). Against the background of maternal DNA, the use of the
      relatively low concentration of cff DNA is limited in NIPD. Therefore, in order
      to overcome the complication of the background of maternal DNA and expand the
      scope of cff DNA application in clinical practice, it is necessary to identify
      novel universal fetal-specific DNA markers. The GeneChip Human Promoter 1.0R
      Array set was used in the present study to analyze the methylation status of 12
      placental tissue and maternal peripheral blood whole-genome DNA samples. In
      total, 5 fetus differential hypermethylation regions and 6 fetus differential
      hypomethylation regions were identified. In order to verify the 11 selected
      methylation regions and detect the differential CpG sites in these regions, a
      bisulfate direct sequencing strategy was used. In total, 87 fetal differential
      methylation CpG sites were identified from 123 CpG sites. The detection of fetal
      differential methylation DNA regions and CpG sites may be instrumental in the
      development of efficient NIPD and in the expansion of its application in other
      disorders.

PMID- 28440506
TI  - Association between high mobility group box-1 protein expression and cell death
      in acute pancreatitis.
AB  - The present study used caerulein stimulation of AR42J rat pancreatic cells as an
      in vitro acute pancreatitis (AP) model to investigate proteins differentially
      expressed in apoptosis and necrosis. AR42J cells were stimulated with 10-8mol/l
      caerulein and incubated for 24 h. Apoptosis and necrosis were detected using flow
      cytometry. The sorted Annexin V-positive cells (apoptotic) and the Annexin
      V/propidium iodide double-positive cells (necrotic) were analysed using
      proteomics. Results showed that numerous proteins were differentially expressed
      in these 2 groups. Functional enrichment analysis was performed on the
      differentially expressed genes using the Database for Annotation, Visualization
      and Integrated Discovery. High mobility group box-1 protein (HMGB1) was
      specifically expressed in the necrosis group. Models of varying degrees of AP
      were established using caerulein at concentrations of 10-9, 10-8, 10-7, 10-6 and
      10-5 mol/l. The percentage of apoptotic and necrotic cells in each group was
      determined using flow cytometry. Protein expression levels of HMGB1 were detected
      by western blot analysis. The present study showed that as the concentration of
      caerulein increased, the percentage of necrotic cells and the protein expression
      levels of HMGB1 increased. HMGB1 is involved in many biological processes,
      including the chromosomal protein glycyl lysine isopeptide cross-link. HMGB1 may
      be involved in the early stage of pancreatitis, potentially by inducing the
      development of cell death by necrosis. These results provide an experimental
      basis for clinical intervention in AP.

PMID- 28440507
TI  - A novel splice-site mutation of WRN (c.IVS28+2T>C) identified in a consanguineous
      family with Werner Syndrome.
AB  - Werner Syndrome (WS) is a rare, adult-onset progeroid syndrome that is associated
      with multiple age-associated complications and relatively short life expectancy.
      The characteristics of WS include a 'bird-like' appearance, canities, cataracts
      and ulcerations around the ankles. In addition, certain patients develop
      hypogonadism with atrophic genitalia and infertility. The average life span of
      affected individuals is 54 years. Previous studies have demonstrated that
      mutations in the Werner syndrome RecQ like helicase gene (WRN) may contribute to
      WS. The present study investigated a consanguineous family with WS, comprising of
      4 generations from Northwest China (Gansu province). A novel homozygous splice
      site mutation in WRN (c.IVS28+2T>C) was identified in this family and was
      predicted to be deleterious. No further relevant mutations were identified by
      direct sequencing of the genes lamin A/C, barrier to autointegration factor 1,
      zinc metallopeptidase STE24 and DNA polymerase Delta1. cDNA sequencing and
      alignments were performed to further confirm the pathogenicity of this mutation.
      The results support the important role of WRN in WS and expand the spectrum of
      known WRN mutations. In addition, it may provide novel approaches in genetic
      diagnosis and counseling of families with WS.

PMID- 28440508
TI  - Expression levels of microRNA-455 and its potential functions by targeting IGF-1R
      in melanoma.
AB  - Melanoma has the highest fatality and malignancy of all skin cancers. In cancer,
      microRNAs (miRNAs) act as tumor suppressors or oncogenes, and inactivation of
      oncogenic miRNAs or restoration of tumor suppressor miRNAs has potential for
      cancer treatment. In the present study, miR-455 expression levels were examined
      in melanoma tissues and cell lines, and miR-455 was significantly downregulated
      in melanoma compared with matched normal tissues or normal epidermal melanocytes.
      In addition, increasing miR-455 expression in melanoma cells reduced cell
      proliferation and invasion. Bioinformatic analysis revealed that insulin-like
      growth factor 1 receptor (IGF-1R) was a putative target of miR-455. Luciferase
      reporter assays, reverse transcription-quantitative polymerase chain reaction and
      western blot confirmed that miR-455 targeted the 3'-untranslated region of IGF-1R
      and thus regulated the biological processes of melanoma cells. IGF-1R knockdown
      resulted in similar effects as miR-455 overexpression in melanoma cells. In
      summary, these findings indicated that miR-455 was downregulated in melanoma, and
      inhibited proliferation and invasion of melanoma cells through directly targeting
      IGF-1R. This also suggested that the restoration of miR-455 may be worth
      investigation as a therapeutic treatment for patients with melanoma.

PMID- 28440509
TI  - Modulation of MMP-2 and -9 secretion by cytokines, inducers and inhibitors in
      human melanoma A-2058 cells.
AB  - Melanoma, an extremely aggressive cancer, causes the most skin cancer-related
      deaths, due to metastasis to other areas of the body, such as lymph nodes, lungs,
      liver, brain or bone. It is characterized by high levels of matrix
      metalloproteinase (MMP)-2 and -9 secretions that degrade the extracellular matrix
      and basement membrane, allowing cancer cells to spread to distal organs. Various
      cytokines, mitogens, growth factors, inducers and inhibitors control MMP
      activities. We investigated the roles of these in regulation of MMP-2 and -9 in
      human melanoma A-2058 cells. Human A-2058 cells were grown in DMEM supplemented
      with 15% FBS and antibiotics in 24-well tissue culture plates. At near
      confluence, the cells were washed with PBS and incubated in serum-free media with
      phorbol 12-myristate 13-acetate (PMA) at 10, 25, 50 and 100 ng/ml; TNF-alpha and
      IL-1beta at 0.1, 1, 10 and 25 ng/ml; LPS at 10, 25, 50 and 100 ug/ml;
      epigallocatechin gallate (EGCG) and doxycycline (Dox) at 10, 25, 50 and 100 uM
      without and with PMA; a nutrient mixture (NM) containing lysine, proline,
      ascorbic acid and green tea extract without and with PMA at 10, 50, 100, 500 and
      1,000 ug/ml; actinomycin D and cyclohexamide at 2 and 4 uM; retinoic acid and
      dexamethasone at 50 uM. After 24 h the media were removed and analyzed for MMP-2
      and MMP-9 by zymography and densitometry. Melanoma A-2058 demonstrated strong
      expression of MMP-2 and slight expression of MMP-9. PMA at 100 ng/ml showed no
      effect on MMP-2 secretion but potently upregulated MMP-9 secretion to 400% that
      of control. TNF-alpha showed no significant overall effect on expression of MMP-2
      but potent dose-dependent increased MMP-9 secretion with 200% of control at 25
      ng/ml. IL-1beta showed no significant effect on MMP-2 or MMP-9 secretion by A
      2058 cells, except at 25 ng/ml where MMP-2 level was reduced by ~40% and MMP-9
      secretion ~50%. LPS treatment showed no significant effect on MMP-2 secretion and
      enhanced MMP-9 secretion up to 25 ug/ml followed by decreased level. EGCG, NM and
      doxycycline, without and with PMA, downregulated the expression of MMP-2 and MMP
      9 in a dose-dependent manner. Actinomycin D, cyclohexamide and retinoic acid had
      inhibitory effects on MMP-2, while dexamethasone showed slight stimulatory effect
      on MMP-2 secretion. Our results showed that select cytokines, mitogens and
      inhibitors modulated A-2058 MMP-2 and MMP-9 expression. They suggest the clinical
      potential of MMP inhibitors, especially the non-toxic ones, such as the nutrient
      mixture and its component EGCG in management of melanoma.

PMID- 28440510
TI  - Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met
      signalling via lamellipodia and filopodia formation.
AB  - The activation of receptor tyrosine kinases (RTKs) results in cellular effects
      including cell proliferation, survival, migration and invasion; RTKs also play an
      important role in tumourigenesis. It has been reported that EGFR signalling
      controls the migration of oral squamous cell carcinoma (OSCC) SAS and HSC3 cells
      but not of HSC4 cells, although the proliferation of HSC4 cells is regulated by
      EGF/EGFR. In the present study, we investigated the roles of EGFR and the c-Met
      signalling pathway in cell migration via filopodia and lamellipodia formation,
      which may be prerequisites for migration. To explore the role of c-Met in cell
      migration, we inhibited c-Met RTK activity using the c-Met inhibitor SU11274 and
      activated c-Met using hepatocyte growth factor (HGF) in three OSCC cell lines
      HSC4, SAS and Ca9-22 and investigated migration potency using a wound healing
      assay. We showed that inhibition of c-Met significantly suppressed, and
      activation of c-Met significantly promoted, the migration of OSCC cells.
      Additionally, the migration of SAS and Ca9-22 cells was inhibited by the EGFR
      inhibitors AG1478 and cetuximab and promoted by EGF treatment. Moreover,
      migration potency was correlated with lamellipodia formation. Furthermore,
      western blot analyses demonstrated that SU11274 decreased and HGF increased
      lamellipodin protein levels as well as phosphorylated c-Met levels. Collectively,
      we demonstrated that c-Met signalling induced lamellipodia formation by
      upregulating lamellipodin, thereby promoting the migration of OSCC cells.

PMID- 28440511
TI  - Simultaneously increased expression of glucocorticoid-induced tumor necrosis
      factor receptor and its ligand contributes to increased interleukin-5/13
      producing group 2 innate lymphocytes in murine asthma.
AB  - Glucocorticoid-induced tumor necrosis factor receptor (GITR) is expressed at high
      levels on CD4+CD25+ regulatory T cells (Tregs). Following activation by its
      ligand (GITRL), GITR influences the activity of effector T cells and Tregs and
      participates in the development of numerous autoimmune and inflammatory diseases,
      including asthma. However, the GITR/GITRL expression level in lung tissue and its
      influence on group 2 innate lymphocytes (ILC2s) in asthma remains unclear. The
      present study detected the number of ILC2s and the expression levels of GITR and
      GITRL in the lung tissues of asthmatic mice by flow cytometry analysis,
      immunofluorescence staining and reverse transcription quantitative polymerase
      chain reaction. The results demonstrated that the number of ILC2s and the
      expression levels of ILC2-associated molecules (interleukin-33 receptor ST2, RAR
      related orphan receptor A and inducible T cell costimulator) were increased in
      the lung tissues of asthmatic mice. The upregulated ILC2s were accompanied by an
      increased number of GITR-positive cells in the spleen and lung tissues, and
      additionally an increased level of GITRL mRNA in lung tissue in asthma. In
      addition, increased mRNA expression levels of interleukin (IL)-5 and IL-13 were
      observed in the asthmatic lung, and there was a significant, positive correlation
      between the mRNA levels of GITR/GITRL and ILC2-associated molecules. Therefore,
      GITRL treatment may increase the number of ILC2s and/or GITR-positive cells in
      lung tissue. These results indicated that the activity of GITR-expressing ILC2s
      may be enhanced via interaction of GITRL and GITR, which may contribute to
      pathogenesis of asthma. These findings present potential therapeutic targets for
      the treatment of asthma.

PMID- 28440512
TI  - Astemizole protects against human umbilical vein endothelial cell injury induced
      by hydrogen peroxide via the p53 signaling pathway.
AB  - Astemizole has gained attention as an antineoplastic drug that targets important
      ion channels. The present study aimed to investigate the protective effects of
      astemizole against hydrogen peroxide (H2O2)-induced oxidative damage to human
      umbilical vein endothelial cells (HUVECs). HUVECs were pretreated with astemizole
      (0.5 and 1 uM) for 12 h, then exposed to H2O2 (200 uM) for 12 h. Cell viability
      was measured using the MTT assay. The levels of malondialdehyde (MDA), superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), reactive oxygen species (ROS)
      and apoptotic percentage were determined. Additionally, the protein expression of
      p53, p21Cip1/Waf1 and p16INK4a was measured by western blot analysis The results
      demonstrated that astemizole (0.5-1 uM) was able to significantly restore the
      viability of HUVECs under oxidative stress and scavenge intracellular ROS induced
      by H2O2. Astemizole also suppressed the production of lipid peroxides, such as
      MDA, and restored the activities of endogenous antioxidants, including SOD and
      GSH-Px, indicating that cell apoptosis may be inhibited. In addition, astemizole
      significantly increased p53, p21Cip1/Waf1 and p16INK4a protein expression. In
      conclusion, astemizole effectively protected endothelial cells against oxidative
      stress induced by H2O2, a function that may involve ROS/p53/p21Cip1/Waf1/
      p16INK4a signaling pathways. The present study therefore served as a preliminary
      investigation into the ROS-protective effects of astemizole, and may pave the way
      for future studies into the development of this compound as a novel therapy for
      atherosclerosis.

PMID- 28440513
TI  - Optimization of antitumor treatment conditions for transcutaneous CO2
      application: An in vivo study.
AB  - Carbon dioxide (CO2) therapy can be applied to treat a variety of disorders. We
      previously found that transcutaneous application of CO2 with a hydrogel decreased
      the tumor volume of several types of tumors and induced apoptosis via the
      mitochondrial pathway. However, only one condition of treatment intensity has
      been tested. For widespread application in clinical antitumor therapy, the
      conditions must be optimized. In the present study, we investigated the
      relationship between the duration, frequency, and treatment interval of
      transcutaneous CO2 application and antitumor effects in murine xenograft models.
      Murine xenograft models of three types of human tumors (breast cancer,
      osteosarcoma, and malignant fibrous histiocytoma/undifferentiated pleomorphic
      sarcoma) were used to assess the antitumor effects of transcutaneous CO2
      application of varying durations, frequencies, and treatment intervals. In all
      human tumor xenografts, apoptosis was significantly induced by CO2 treatment for
      >=10 min, and a significant decrease in tumor volume was observed with CO2
      treatments of >5 min. The effect on tumor volume was not dependent on the
      frequency of CO2 application, i.e., twice or five times per week. However,
      treatment using 3- and 4-day intervals was more effective at decreasing tumor
      volume than treatment using 2- and 5-day intervals. The optimal conditions of
      transcutaneous CO2 application to obtain the best antitumor effect in various
      tumors were as follows: greater than 10 min per application, twice per week, with
      3- and 4-day intervals, and application to the site of the tumor. The results
      suggest that this novel transcutaneous CO2 application might be useful to treat
      primary tumors, while mitigating some side effects, and therefore could be safe
      for clinical trials.

PMID- 28440514
TI  - Silibinin downregulates MMP2 expression via Jak2/STAT3 pathway and inhibits the
      migration and invasive potential in MDA-MB-231 cells.
AB  - Worldwide, breast cancer (BCa) is the most common cancer in women. Among its
      subtypes, triple-negative breast cancer (TNBC) is an aggressive form associated
      with diminished survival. TNBCs are characterized by their absence, or minimal
      expression, of the estrogen and progesterone receptors, as well as the human
      epidermal growth factor receptor 2 (i.e. ER-/-, PR-/-, Her2-/Low). Consequently,
      treatment for this subtype of BCa remains problematic. Silibinin, a derivative of
      the flavonoid silymarin, is reported to have anticancer activities against
      hepatic and non-small cell lung cancers. We hypothesized that silibinin might
      inhibit cell-extracellular matrix interactions via the regulation, expression,
      and activation of STAT3 in TNBCs, which could directly inhibit metastasis in
      silibinin-treated BCa cells. Using proliferation assays, we found that exposure
      to silibinin at a concentration of 200 uM inhibited the proliferation of breast
      cancer (BCa) cells; this concentration also inhibited phosphorylation of STAT3
      and its principal upstream kinase, Jak2. Furthermore, we found that silibinin
      inhibited the nuclear translocation of STAT3, as well as its binding to the MMP2
      gene promoter. The ability of silibinin to inhibit metastasis was further studied
      using an in vitro invasion assay. The results confirm the role of STAT3 as a
      critical mediator in the invasive potential of BCa cells, and STAT3 knock-down
      resulted in inhibition of invasion. The invasion ability of silibinin-treated BCa
      cells was studied in detail with the expression of MMP2. Prevention of STAT3
      activation also resulted in the inhibition of MMP2 expression. Use of a small
      interfering RNA to knock down STAT3 (siSTAT3) allowed us to confirm the role of
      STAT3 in regulating MMP2 expression, as well as the mechanism of action of
      silibinin in inhibiting MMP2. Taken together, we found that silibinin inhibits
      the Jak2/STAT3/MMP2 signaling pathway, and inhibits the proliferation, migration,
      and invasion of triple-negative BCa cells.

PMID- 28440516
TI  - [Current status and changes of metabolic and bariatric surgery in China].
AB  - Through continuous development, metabolic and bariatric surgery (MBS) has become
      widely recognized in academic and medical circles. In China, the volume of MBS
      operations has increased year by year. Therapeutic goals of MBS have evolved from
      treating obesity to treating Type 2 diabetes mellitus, and further to treating a
      series of obesity-associated metabolic diseases (including conditions in the
      endocrine system, circulatory system, respiratory system, reproductive system,
      and etc). Surgical approach of MBS has also been evolving continuously. Currently
      the common surgical procedures include laparoscopic Roux-en-Y gastric bypass
      (LRYGB), laparoscopic sleeve gastrectomy (LSG), laparoscopic adjustable gastric
      banding (LAGB) and bilio-pancreatic diversion with duodenal switch (BPD-DS). All
      surgical procedures have pros and cons, and the choice of surgical procedures
      should be based on the conditions of patients, the surgeon's technical ability,
      and benefits and operative risks. With the development of MBS, the proportions of
      different surgical procedures also changed in China. In recent five years, the
      proportion of AGB has decreased continuously and LAGB is no longer a common
      procedure. The proportion of LSG has increased rapidly, rising from 9% in 2010 to
      55% in 2015. The proportion of RYGB has increased from 57% to 64% between 2010
      and 2013, and remained at 45% afterwards. Since 2010, most MBS operations are
      laparoscopic surgery. 3D Laparoscopic surgery, laparoendoscopic single-site
      surgery and da Vinci Robotic Surgery have also been introduced in MBS. This
      review discusses the status quo and changes of MBS in china, as well as the new
      technology in MBS, aiming to strengthen the information and comprehension of MBS
      in china.

PMID- 28440515
TI  - [Interpretation of the International Joint Statement on Metabolic Surgery in the
      Treatment Algorithm for Type 2 Diabetes].
AB  - Along with the soaring prevalence of obesity and type 2 diabetes mellitus (T2DM)
      globally, metabolic and bariatric surgery (MBS) has been rapidly developing into
      a major surgical subspecialty. However, the indications, benefits and potential
      risks of MBS are still controversial so far. In September 2015, the 2nd Diabetes
      Surgery Summit (DSS-II() was successfully convened, and later on an international
      joint statement on metabolic surgery in the treatment algorithm for T2DM was
      released based upon the consensus reached in DSS-II(, aiming to serve as a new
      global clinical guideline. The DSS-II( joint statement was initiated and endorsed
      by 5 leading international diabetes organizations, including American Diabetes
      Association (ADA), International Diabetes Federation (IDF), Chinese Diabetes
      Society (CDS), Diabetes India, as well as Diabetes UK, and was developed by an
      expert committee comprised of 48 international authorities as voting delegates.
      Up to the date of publication, the DSS-II( statement has been officially endorsed
      by 45 international professional associations/societies, including 30 non
      surgical and 15 surgical organizations. In this statement, the following six
      aspects were recommended to differentiate MBS from traditional bariatric surgery:
      1)The primary goal of MBS is to treat T2DM and to reduce the risk of T2DM
      complications; 2) In addition to a 50% or more of excess weight loss and
      normalization of glycemia, outcomes of diabetes complications should also be
      considered as clinical endpoints of MBS; 3) For patient selection, body mass
      index (BMI), T2DM treatment, as well as long-term risks versus benefits,
      including its effects on cardiovascular events (CVD), should all be considered;
      4) T2DM and its complications, as well as pancreatic function reserve should be
      assessed pre-operatively; 5) Major surgical options include laparoscopic Roux-en
      Y gastric bypass (LRYGB), laparoscopic sleeve gastrectomy (LSG), laparoscopic
      adjustable gastric banding (LAGB), and bilio-pancreatic diversion with duodenal
      switch(BPD-DS). BPD-DS has the best outcome in T2DM remission followed by LRYGB,
      LSG and LAGB; 6) Glycemic variation should be intensively monitored, and if
      needed, managed following surgery. Clinical follow-up should be conducted at
      least once every six months within two years after surgery. For patients
      achieving complete remission from T2DM, diabetes complications should still be
      monitored within five years after surgery with the same frequency and protocols
      as pre-operatively.

PMID- 28440517
TI  - [Efficacy and future of endoscopic bariatric surgery in the treatment of obesity
      and metabolic diseases].
AB  - The emerging endoscopic technologies are proved to be effective treatments for
      obesity in selected patients and to offer the potential advantages of reduced
      invasiveness, reversibility and repeatability. From the view of operation
      principle, endoscopic technologies can be classified as restrictive procedure,
      malabsorption procedure and endoscopic revision of gastric bypass. Restrictive
      procedures include intragastric balloon, aspiration therapy, endoscopic sleeve
      gastroplasty (ESG) and transoral gastroplasty. Intragastric balloon employs space
      occupying, volume restriction and satiety mechanisms, which is superior to drugs
      and lifestyle change, but shorter than sleeve and bypass surgery. Aspiration
      therapy is similar to standard percutaneous endoscopic gastrostomy, while there
      are no available data regarding the obesity and metabolic improvement. Compared
      with traditional bariatric surgery, ESG does not excise gastric tissue with less
      complications and without weight regain, but it can not be used as an independent
      operation still now. Transoral gastroplasty is rarely applied clinically whose
      efficacy and long-term complications need further studies. Malabsorption surgery
      includes endoscopic duodenojejunal bypass sleeve (EDJBS) and endoscopic
      gastroduodenojejunal bypass sleeve(EGDJBS). EDJBS may have the similar mechanism
      like bypass reducing the blood glucose. Even with obvious effect of weight loss,
      EDJBS has high morbidity of complications and requirements of the skilled
      operators. EGDJBS, which imitates bypass anatomy changes and belongs to the mixed
      operation, should be superior to the above procedures in reducing weight
      theoretically, but due to the lack of clinical data, its short-term and long-term
      efficacy still need further clinical observation. As compared to the complexity
      and risks associated with telescopic surgical revision, endoscopic suturing has
      been confirmed as less invasive and safer for stomal revisions, while its long
      term efficacy of reducing weight and improvement of diabetes are not yet clear.
      Even if long-term efficacy of reducing weight and morbidity of complication in
      endoscopic bariatric surgery are still indefinite, and clinical trial researches
      of large sample and long-term follow-up are absent, with the development of
      endoscopic skill and the gradual clinical application, endoscopic bariatric
      surgery will provide a new option for the patients of obesity and metabolic
      diseases.

PMID- 28440518
TI  - [Choice of bariatric and metabolic surgical procedures].
AB  - Bariatric and metabolic surgery has become the clinical hot topic of the
      treatment of metabolic syndromes including obesity and diabetes mellitus, but how
      to choose the appropriate surgical procedure remains the difficult problem in
      clinical practice. Clinical guidelines of American Society for Metabolic and
      Bariatric Surgery(ASMBS)(version 2013) introduced the procedures of bariatric and
      metabolic surgery mainly including biliopancreatic diversion with duodenal
      switch(BPD-DS), laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux
      en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy(LSG). To choose
      the appropriate bariatric and metabolic procedure, the surgeons should firstly
      understand the indications and the contraindications of each procedure. Procedure
      choice should also consider personal condition (body mass index, comorbidities
      and severity of diabetes), family and socioeconomic status (postoperative follow
      up attendance, understanding of potential surgical risk of gastrectomy and
      patient's will), family and disease history (patients with high risk of gastric
      cancer should avoid LRYGB; patients with gastroesophageal reflux disease should
      avoid LSG) and associated personal factors of surgeons. With the practice of
      bariatric and metabolic surgery, the defects, especially long-term complications,
      of different procedures were found. For example, LRYGB resulted in higher
      incidence of postoperative anemia and marginal ulcer, high risk of gastric cancer
      as well as the requirement of vitamin supplementation and regular follow-up.
      Though LSG has lower surgical risk, its efficacy of diabetes mellitus remission
      and long-term weight loss are inferior to the LRYGB. These results pose
      challenges to the surgeons to balance the benefits and risks of the bariatric
      procedures. A lot of factors can affect the choice of bariatric and metabolic
      procedure. Surgeons should choose the procedure according to patient's condition
      with the consideration of the choice of patients. The bariatric and metabolic
      surgery not only manages the diabetes mellitus and weight loss, but also results
      in the reconstruction of gastrointestinal tract and side effect. Postoperative
      surgical complications and nutritional deficiency should also be considered.
      Thereby, individualized bariatric procedure with the full consideration of each
      related factors is the ultimate objective of bariatric and metabolic surgery.

PMID- 28440520
TI  - [Effect of laparoscopic sleeve gatrectomy on type 2 diabetes mellitus in obese
      patients with body mass index less than 40 kg/m2].
AB  - OBJECTIVE: To evaluate the effect of laparoscopic sleeve gastrectomy(LSG) on type
      2 diabetes mellitus (T2DM) in patient with a body mass index(BMI) less than 40
      kg/m2. METHODS: Twenty four obese patients with T2DM and BMI less than 40 kg/m2
      received LSG between 1 January 2011 and 1 September 2013 at the Department of
      General Surgery in Chinese PLA General Hospital. The clinical data and 3-year
      follow-up outcomes regarding weight loss and remission of diabetes were
      retrospectively analyzed. RESULTS: There were 10 males and 14 females with a
      median age of 40.8(35 to 48) years. The preoperative body weight and BMI
      was(99.9+/-15.0) kg and (34.4+/-2.8) kg/m2, respectively. The median duration of
      type 2 diabetes was 4.3(2 to 15) years. The preoperative fasting blood glucose
      and glycosylated hemoglobin(HbAlc) was (11.4+/-1.3) mmol/L and (8.7+/-0.8)%,
      respectively. All these patients were preoperatively diagnosed as T2DM by the
      multidisciplinary experts of the surgical treatment team for obesity and diabetes
      in our center. All these patients were eligible for surgical treatment through
      the screening and evaluation by the multidisciplinary joint outpatient service.
      All the procedures were successfully completed without conversion to laparotomy.
      There were no severe postoperative complications. The mean fasting blood glucose
      was (6.4+/-1.8) mmol/L, (6.1+/-1.7) mmol/L, (6.0+/-1.5) mmol/L, (5.9+/-1.4)
      mmol/L and (6.0+/-1.4) mmol/L, respectively, at 6, 9, 12, 24 and 36 months after
      operation. The mean HbA1c in the same observation intervals was (6.6+/-1.1)%,
      (6.2+/-1.2)%, (6.1+/-1.2)%, (6.0+/-1.3)% and (6.1+/-1.3)%, respectively. The body
      weight was (89.4+/-11.4) kg, (86.3+/-10.6) kg, (83.1+/-10.2) kg,(80.6+/-9.8) kg
      and (81.3+/-10.1) kg, respectively. The corresponding BMI was (30.8+/-1.6) kg/m2,
      (29.8+/-1.5) kg/m2, (28.7+/-1.5) kg/m2, (27.8+/-1.8) kg/m2 and (28.1+/-1.8)
      kg/m2, respectively. The %EWL was (36.7+/-8.7)%, (47.6+/-12.5)%, (58.8+/-16.4)%,
      (67.2+/-20.3)% and (64.8+/-21.5)%, respectively. The overall remission rate of
      diabetes at 6, 9, 12, 24 and 36 months was 50.0%(12/24), 79.2%(19/24),
      70.8%(17/24), 66.7%(16/24) and 62.5%(15/24), respectively. The complete remission
      rate was 33.3%(8/24), 50.0%(12/24), 54.2%(13/24), 45.8%(11/24) and 50.0%(12/24),
      respectively. For patients with a duration of T2DM shorter than 5 years, the
      overall remission rate at 9, 12 and 24 months after operation was 10/10, 9/10 and
      9/10, respectively, significantly higher than that of patients with a duration of
      11-15 years (2/6, 2/6 and 2/6, Fisher's exact tests, P=0.008, 0.036 and 0.036,
      respectively). CONCLUSION: The present study confirms the efficacy of LSG in the
      treatment of T2DM patients with a BMI less than 40 kg/m2.

PMID- 28440519
TI  - [Prevention, diagnosis and treatment of perioperative complications of bariatric
      and metabolic surgery].
AB  - Surgical operation in treating obesity and type 2 diabetes is popularizing
      rapidly in China. Correct prevention and recognition of perioperation-related
      operative complications is the premise of ensuring surgical safety. Familiar
      complications of the operation include deep venous thrombosis, pulmonary artery
      embolism, anastomotic bleeding, anastomotic fistula and marginal ulcer. The
      prevention of deep venous thrombosis is better than treatment. The concrete
      measures contain physical prophylaxis (graduated compression stocking and
      intermittent pneumatic compression leg sleeves) and drug prophylaxis
      (unfractionated heparin and low molecular heparin), and the treatment is mainly
      thrombolysis or operative thrombectomy. The treatment of pulmonary artery
      embolism includes remittance of pulmonary arterial hypertension, anticoagulation,
      thrombolysis, operative thrombectomy, interventional therapy and extracorporeal
      membrane oxygenation (ECMO). Hemorrhage is a rarely occurred but relatively
      serious complication after bariatric surgery. The primary cause of anastomotic
      bleeding after laparoscopic gastric bypass is incomplete hemostasis or weak
      laparoscopic repair. The common bleeding site in laparoscopic sleeve gastrectomy
      is gastric stump and close to partes pylorica, and the bleeding may be induced by
      malformation and weak repair technique. Patients with hemodynamic instability
      caused by active bleeding or excessive bleeding should timely received surgical
      treatment. Anastomotic fistula in gastric bypass can be divided into
      gastrointestinal anastomotic fistula and jejunum-jejunum anastomotic fistula. The
      treatment of postoperative anastomotic fistula should vary with each individual,
      and conservative treatment or operative treatment should be adopted. Anastomotic
      stenosis is mainly related to the operative techniques. Stenosis after sleeve
      gastrectomy often occurs in gastric angle, and the treatment methods include
      balloon dilatation and stent implantation, and surgical treatment should be
      performed when necessary. Marginal ulcer after gastric bypass is a kind of peptic
      ulcer occurring close to small intestine mucosa in the junction point of stomach
      and jejunum. Ulcer will also occur in the vestige stomach after laparoscopic
      sleeve gastrectomy, and the occurrence site locates mostly in the gastric antrum
      incisal margin. Preoperative anti-HP (helicobacter pylorus) therapy and
      postoperative continuous administration of proton pump inhibitor (PPI) for six
      months is the main means to prevent and treat marginal ulcer. For patients on
      whom conservative treatment is invalid, endoscopic repair or surgical repair
      should be considered. Different surgical procedures will generate different
      related operative complications. Fully understanding and effectively dealing with
      the complications of various surgical procedures through multidisciplinary
      cooperation is a guarantee for successful operation.

PMID- 28440521
TI  - [Effect of laparoscopic sleeve gastrectomy on sex hormone in male severe
      obesity].
AB  - OBJECTIVE: To investigate the effect of laparoscopic sleeve gastrectomy(LSG) on
      sex hormone in male patients with severe obesity. METHODS: Retrospective analysis
      was performed in 31 male patient with severe obese [body mass index(BMI) >=28
      kg/m2, obesity group] who underwent LSG in Shanghai Tenth People's Hospital of
      Tongji University from December 2012 to May 2016. The anthropometric
      parameters(weight, BMI, waist circumference, hip circumference, waist-hip ratio,
      body fat percentage), glucose metabolic indices [fasting plasma glucose(FPG),
      fasting insulin (FINS), glycosylated hemoglobin (HbA1c), homeostasis model
      assessment-insulin resistance index(HOMA-IR)], and sex hormone parameters
      [estradiol(E2), total testosterone (TT), follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH)] were collected preoperatively and 1, 3, 6 months
      postoperatively. In addition, 31 healthy male volunteers with normal BMI were
      consecutively recruited in this study as control group. The above-mentioned
      parameters were also determined in control group. Changes of these variables
      before and after surgery were analyzed. Pearson method was used to analyze the
      correlation of TT with anthropometric parameters and glucose metabolic indices
      before and after surgery. RESULTS: The average age of patients in obesity and
      control group was (32.9+/-9.7) (18 to 56) years and (30.7+/-8.9) (18 to 49)
      years. Compared to the control group, obesity group had significantly higher
      anthropometric parameters and glucose metabolic indices before surgery (all
      P<0.05). In obesity group, the anthropometric and glucose metabolic indices
      significantly decreased at 1 to 6 months after surgery compared to those before
      surgery (all P<0.05). At 1 month after surgery, the anthropometric parameters and
      glucose metabolic indices in obesity group were significantly higher than those
      in control group (all P<0.05). At 3, and 6 months after surgery, there were no
      significant differences in glucose metabolic indices between obesity and control
      group (all P>0.05), while the anthropometric parameters in obesity group were
      still significantly higher than those in control group(all P<0.05). The sex
      hormone parameters in control and obesity group before surgery were as follows:
      E2: (100.2+/-23.5) pmol/L and (129.2+/-81.9) pmol/L; TT: (18.0+/-4.9) nmol/L and
      (8.4+/-4.5) nmol/L; FSH: (4.5+/-3.1) IU/L and (4.3+/-2.5) IU/L; LH: (4.4+/-1.7)
      IU/L and (5.3+/-2.6) IU/L. Compared to control group, the TT level of obese
      patients before surgery significantly decreased(P=0.000), while no significant
      differences were observed in the levels of E2, FSH, and LH(all P>0.05). The TT
      levels were significantly increased at 1, 3, 6 months after surgery[(13.1+/-7.0),
      (13.6+/-5.7), (21.0+/-19.3) nmol/L, respectively, all P<0.05] and the E2 level
      was significantly decreased at 6 months after surgery [(91.4+/-44.9) pmol/L,
      P<0.05], while no significant differences were observed at 1 and 3 months after
      surgery (all P>0.05). Furthermore, the FSH and LH levels did not exhibit
      significant change at 1, 3, and 6 months after surgery compared to those before
      surgery (all P>0.05). At 1 month after surgery, no significant correlations were
      examined in the change value of TT levels (?TT) with the changes of BMI(?BMI),
      FPG(?FPG), FINS(?FINS), HOMA-IR(?HOMA-IR), and E2(?E2) (all P>0.05). At 3 months
      after surgery, ?TT was negatively correlated with ?BMI (r=-0.441, P=0.015), ?FINS
      (r=-0.375, P=0.041), and ?HOMA-IR(r=-0.397, P=0.030), but not correlated with
      ?FPG and ?E2 (all P>0.05). At 6 months after surgery, ?TT was negatively
      correlated with ?BMI(r=-0.510, P=0.018) and ?HOMA-IR (r=-0.435, P=0.049), but not
      correlated with ?FPG, ?FINS and ?E2 (all P>0.05). CONCLUSIONS: Male severe obese
      patients are accompanied with abnormal sex hormone levels. LSG has a significant
      effect on weight loss and blood glucose improvement, and may ameliorate the sex
      hormone unbalance by improving the insulin resistance in men with severe obesity.

PMID- 28440522
TI  - [Nutrition management in obese patients with type 2 diabetes mellitus after
      laparoscopic sleeve gastrectomy].
AB  - OBJECTIVE: To explore the value of nutrition management in obese patients with
      type 2 diabetes mellitus(T2DM) after laparoscopic sleeve gastrectomy(LSG).
      METHODS: Clinical data of 22 obese T2DM patients undergoing LSG from March 2013
      to July 2015 in Fudan University Pudong Medical Center were collected. All the
      patients strictly followed the specialized instruction by nutritionists: diabetic
      and low calorie diet 3347.2 to 5020.8 kJ (800 to 1200 kcal) per day before the
      operation; low calorie liquid diet 2510.4 kJ(600 kcal) per day before operation
      for promoting gastric emptying; fasting diet before postoperative ventilation;
      clear liquid diet 1673.6 to 2510.4 kJ (400 to 600 kcal) per day after
      postoperative ventilation (liquid intake >2000 ml); low fat liquid diet 2928.8 to
      3765.6 kJ (700 to 900 kcal) per day (protein 60 g per day at least, 2000 ml
      liquid) 2 weeks after the operation; semi-liquid diet 1 month after operation and
      gradually normal diet. All the 22 patients were followed up at 1 week, 1, 3, 6
      months after operation on time. Changes of body weight, waist circumference, hip
      circumference, body mass index(BMI), blood glucose indexes induding fasting blood
      glucose(FBG), 2-hour postparandial blood glucose(PBG), fasting C-peptide, 2-hour
      postprandial C-peptide, fasting serum inculin(FINS), 2-hour postprandial
      inculin(INS), HbAlc, blood pressure and blood lipid indexes were observed and
      analyzed before and 1 week, 1, 3, 6 months after operation. RESULTS: The average
      age of 22 patients (10 men and 12 women) was 38.6 years (18 to 66 years). The
      duration of diabetes varied from 1 month to 15 years. Comorbidity included 12
      patients of high blood pressure, 14 of fatty liver, 1 of coronary heart disease,
      1 of gout, 1 of chronic thyroiditis and 1 of menstrual disorder. LSG was
      performed successfully in all the patients and no severe complications and
      transference to laparotomy occurred. As compared to pre-operation, at 6 months
      after operation, the average body weight decreased from (103.9+/-20.2) kg to
      (80.9+/-12.6) kg (t=6.294, P=0.000), waist circumference from (118.6+/-13.8) cm
      to (96.4+/-8.0) cm (t=6.331, P=0.000), hip circumference from (116.9+/-12.6) cm
      to (104.0+/-7.7) cm (t=3.854, P=0.000), BMI from (36.2+/-5.9) kg/m2 to (27.9+/
      3.5) kg/m2 (t=5.630, P=0.000), showing a decreasing trend over time. There was no
      underweight patient after 6 months follow-up. As compared to pre-operation, at 6
      months after operation, the average FBG reduced from (7.4+/-1.4) mmol/L to (6.0+/
      0.9) mmol/L (t=3.172, P=0.003), 2 h PBG from (14.1+/-4.9) mmol/L to (7.5+/-2.2)
      mmol/L (t=7.026, P=0.000), FINS from (160.0+/-71.9) mIU/L to (43.8+/-20.8) mIU/L
      (t=7.259, P=0.000), 2-hour postprandial INS from (437.6+/-261.4) mIU/L to
      (140.5+/-104.6) mIU/L (t=5.858, P=0.000), fasting C-peptide from (1.1+/-0.6)
      MUg/L to (0.7+/-0.3) MUg/L (t=3.560, P=0.000), 2-hour postprandial C-peptide from
      (2.5+/-0.9) MUg/L to (1.5+/-0.7) MUg/L (t=3.865, P=0.000), HbAlc from (8.0+/
      1.6)% to (5.9+/-0.6)% (t=5.953, P=0.000), showing a decreasing trend over time
      except FBG, 2h postprandial C-peptide and HbAlc(all P<0.05). FBG and 2-hour PBG
      of 16 patients returned to normal 3 months after the operation. Blood pressure
      and trigly ceride decreased obviously 6 months after operation compared to pre
      operation with significant difference(P<0.05). At 6 months after operation, blood
      pressure of 8 comorbidity patients with high blood pressure became normal (8/12,
      66.7%) and of 4 patients improved(4/12, 33.3%); B ultrasound examination revealed
      normal in 11 comorbidity patients with fatty liver(11/14,78.6%) and improvement
      in 3 patients (3/14,15.4%). Blood uric acid of the gout patient and the
      menstruation of the menstrual disorder patient returned to normal 3 months and 1
      month after the operation respectively. CONCLUSION: As for obese patients with
      T2DM undergoing LSG, reasonable nutrition management is helpful to decrease body
      weight, and to obtain an ideal improvement of blood glucose and blood lipid
      levels.

PMID- 28440523
TI  - [Outcome of watch and wait strategy or organ preservation for rectal cancer
      following neoadjuvant chemoradiotherapy: report of 35 cases from a single cancer
      center].
AB  - OBJECTIVE: To investigate the safety and efficacy of organ preservation surgery
      or "watch and wait" strategy for rectal cancer patients who are evaluated as
      clinical complete response(cCR) or near-cCR following neoadjuvant
      chemoradiotherapy (nCRT). METHOD: From March 2011 to June 2016, 35 patients with
      mid-low rectal cancers who were diagnosed as cCR or near-cCR following nCRT
      underwent organ preservation surgery with local excision or surveillance
      following "watch and wait" strategy in the Peking University Cancer Hospital. All
      the patients received re-evaluation and re-staging 6-12 weeks after the
      completion of nCRT, according to Habr-Gama and MSKCC criteria for the diagnosis
      of cCR or near-cCR. The near-cCR patients who received local excision and were
      pathologically diagnosed as T0Nx were also regarded as cCR. The end-points of
      this study included organ-preservation rate (OPR), sphincter-preservation rate
      (SPR), non-re-growth disease-free survival (NR-DFS), stoma-free survival, cancer
      specific survival (CSS) and overall survival(OS). Kaplan-Meier curve was used to
      estimate the survival data at 3 years. RESULTS: A total of 35 cases were analyzed
      including 24 males (68.6%) and 11 females (31.4%). The median age was 60 (range
      37-79) years and the median distance from tumor to anal edge was 4(2-8) cm.
      Thirty-three patients received 50.6 Gy/22f IMRT with capecitabine and two
      patients received 50 Gy/25f RT with capecitabine. The cCR and near-cCR rates were
      74.3%(26/35) and 25.7%(9/35) respectively. Excision biopsy was performed in 4
      near-cCR cases to confirm the diagnosis of cCR. The non-re-growth DFS rate was
      14.3%(5/35) and the median time of tumor re-growth was 6.7 (4.7-37.4) months. In
      five patients with tumor re-growth, four were salvaged by radical rectal
      resections and one received local excision. The distant metastasis rate was
      5.7%(2/35), one patient presented resectable liver metastasis and received
      radical resection, another patient presented multiple bone metastases and was
      still alive. The median follow-up time was 43.7(6.1-71.4) months. At three years,
      the organ-preservation rate was 88.6%(31/35), the sphincter-preservation rate was
      97.1% (34/35). No local recurrence was observed in five patients who received
      salvage surgery. The non-re-growth DFS was 94.0%. Three patients died of non
      rectal cancer related events. The cancer-specific survival was 100%, the overall
      survival was 92.7% and the stoma-free survival rate was 90.0%. CONCLUSIONS: Organ
      preservation surgery or "watch and wait" strategy for cCR or near-cCR patients is
      feasible and achieves good outcomes. This strategy can be an alternative to
      standard care, improve patient's quality of life and facilitate tailored
      treatment for mid-low rectal cancer following nCRT, however, it should be
      cautiously applied in near-cCR patients before local excision biopsy.

PMID- 28440524
TI  - [Clinical epidemiological characteristics and change trend of upper
      gastrointestinal bleeding over the past 15 years].
AB  - OBJECTIVE: To investigate the clinical epidemiology change trend of upper
      gastrointestinal bleeding (UGIB) over the past 15 years. METHODS: Consecutive
      patients who was diagnosed as continuous UGIB in the endoscopy center of The
      First Affiliated Hospital of Sun-Yat University during the period from 1 January
      1997 to 31 December 1998 and the period from 1 January 2012 to 31 December 2013
      were enrolled in this study. Their gender, age, etiology, ulcer classification,
      endoscopic treatment and hospitalization mortality were compared between two
      periods. RESULTS: In periods from 1997 to 1998 and 2012 to 2013, the detection
      rate of UGIB was 9.99%(928/9 287) and 4.49%(1 092/24 318)(chi2=360.089, P=0.000);
      the percentage of male patients was 73.28%(680/928) and 72.44% (791/1 092)
      (chi2=0.179, P=0.672), and the onset age was (47.3+/-16.4) years and (51.4+/
      18.2) years (t=9.214, P=0.002) respectively. From 1997 to 1998, the first
      etiology of UGIB was peptic ulcer bleeding, accounting for
      65.2%(605/928)[duodenal ulcer 47.8%(444/928), gastric ulcer 8.3%(77/928), stomal
      ulcer 2.3%(21/928), compound ulcer 6.8%(63/928)],the second was cancer
      bleeding(7.0%,65/928), and the third was esophageal and gastric varices bleeding
      (6.4%,59/928). From 2012 to 2013, peptic ulcer still was the first cause of UGIB,
      but the ratio obviously decreased to 52.7%(575/1092)(chi2=32.467,
      P=0.000)[duodenal ulcer 31.9%(348/1092), gastric ulcer 9.4%(103/1092), stomal
      ulcer 2.8%(30/1092), compound ulcer 8.6%(94/1092)]. The decreased ratio of
      duodenal ulcer bleeding was the main reason (chi2=53.724, P=0.000). Esophageal
      and gastric varices bleeding became the second cause (15.1%,165/1 092,
      chi2=38.976, P=0.000), and cancer was the third cause (9.2%,101/1 092,
      chi2=3.352, P=0.067). The largest increasing amplitude of the onset age was
      peptic ulcer bleeding [(46.2+/-16.7) years vs. (51.9+/-18.9) years, t=-5.548,
      P=0.000), and the greatest contribution to the amplitude was duodenal ulcer
      bleeding [(43.4+/-15.9) years vs. (48.4+/-19.4) years, t=-3.935, P=0.000], while
      the onset age of esophageal and gastric varices bleeding [(49.8+/-14.1) years vs.
      (48.8+/-13.9) years, t=0.458, P=0.648] and cancer [(58.4+/-13.4) years vs.
      (58.9+/-16.7) years, t=-0.196, P=0.845] did not change significantly. Compared
      with the period from 1997 to 1998, the detection rate of high risk peptic ulcer
      rebleeding (Forrest stage I(a, I(b, II(a and II(b) increased (chi2=39.958,
      P=0.000) in the period from 2012 to 2013. From 1997 to 1998, 54 patients
      underwent endoscopic treatment, and the achievement ratio of hemostasis was 79.6%
      (43/54). From 2012 to 2013, 261 patients underwent endoscopic treatment and the
      achievement ratio of hemostasis was 96.9%(253/261), which was significantly
      higher (chi2=23.287, P=0.000). Compared to the period from 1997 to 1998, more
      patients with variceal bleeding or non-variceal bleeding received endoscopic
      treatment in time (39.0% vs. 70.3%, chi2=51.930, P=0.000; 3.6% vs. 15.6%,
      chi2=62.292, P=0.000, respectively), and higher ratio of patients staging Forrest
      stage I(a to II(b also received endoscopic treatment in the period from 2012 to
      2013 [27.4%(26/95) vs. 68.5%(111/162), chi2=40.739, P=0.000]. More qualified
      endoscopic hemostatic techniques were used, containing thermocoagulation (0 vs.
      15.2%, chi2=79.518, P=0.000), hemostatic clip (0 vs. 55.9%, chi2=20.879,
      P=0.000), hemostatic clip combined with thermocoagulation (4.3% vs. 16.4%,
      chi2=5.154, P=0.023), while less single injection was used (87.1% vs. 6.2%,
      chi2=10.420, P=0.001), and single spraying for hemostasis was completely
      abandoned in the period from 2012 to 2013. The ratio of inpatients undergoing
      reoperation decreased obviously in the period from 2012 to 2013 [9.3%(86/928) vs.
      6.0%(65/1092), chi2=7.970, P=0.005], while no significant difference was found in
      mortality during hospitalization between two periods. CONCLUSION: Compared with
      the period from 1997 to1998, the mean onset age of UGIB increased, and the ratio
      of peptic ulcer bleeding decreased due to the reduction of duodenal ulcer
      bleeding, the detection rate of high risk peptic ulcer rebleeding increased, the
      cure rate of endoscopic treatment for UGIB increased, more reasonable and
      immediate hemostatic methods were used, but overall mortality did not change
      obviously in the period from 2012 to 2013.

PMID- 28440525
TI  - [Treatment of complications after laparoscopic intersphincteric resection for low
      rectal cancer].
AB  - OBJECTIVE: To summarize the perioperative and postoperative complications follow
      laparoscopic intersphincteric resection (LapISR) in the treatment of low rectal
      cancer and their management. METHODS: An observational study was conducted in 73
      consecutive patients who underwent LapISR for low rectal cancer between June 2011
      and February 2016 in our hospital. The clinicopathological parameters,
      perioperative and postoperative complications, and clinical outcomes were
      collected from a prospectively maintained database. Perioperative and
      postoperative complications were defined as any complication occurring within or
      more than 3 months after the primary operation, respectively. RESULTS: Forty
      nine(67.1%) cases were male and 24(32.9%) were female with a median age of 61(25
      to 79) years. The median distance from distal tumor margin to anal verge was
      4.0(1.0 to 5.5) cm. The median operative time was 195 (120 to 360) min, median
      intra operative blood loss was 100 (20 to 300) ml, median number of harvested
      lymph nodes was 14(3 to 31) per case. All the patients underwent preventive
      terminal ileum loop stoma. No conversion or hospital mortality was presented. The
      R0 resection rate was 98.6% with totally negative distal resection margin. A
      total of 34 complication episodes were recorded in 21(28.8%) patients during
      perioperative period, and among which 20.6%(7/34) was grade III(-IIII( according
      to Dindo system. Anastomosis-associated morbidity (16.4%,12/73) was the most
      common after LapISR, including mucosa ischemia in 9 cases(12.3%), stricture in 7
      cases (9.6%, 4 cases secondary to mucosa necrosis receiving anal dilation), grade
      A fistula in 3 cases (4.1%) receiving conservative treatment and necrosis in 1
      case (1.4%) receiving permanent stoma. After a median follow up of 21(3 to 60)
      months, postoperative complications were recorded in 12 patients (16.4%) with 16
      episodes, including anastomotic stenosis (8.2%), rectum segmental stricture
      (5.5%), ileus (2.7%), partial anastomotic dehiscence (1.4%), anastomotic fistula
      (1.4%), rectovaginal fistula (1.4%) and mucosal prolapse (1.4%). These patients
      received corresponding treatments, such as endoscopic transanal resection, anal
      dilation, enema, purgative, permanent stoma, etc. according to the lesions. Six
      patients (8.2%) required re-operation intervention due to postoperative
      complications. CONCLUSION: Anastomosis-associated morbidity is the most common
      after LapISR in the treatment of low rectal cancer in perioperative and
      postoperative periods, which must be strictly managed with suitable methods.

PMID- 28440526
TI  - [Application of three-stitch preventive transverse colostomy in anterior
      resection of low rectal cancer].
AB  - OBJECTIVE: To explore the application of three-stitch preventive transverse
      colostomy in anterior resection of low rectal cancer. METHOD: From May 2015 to
      March 2016, 70 consecutive low rectal cancer patients undergoing anterior
      resection and preventive transverse colostomy in our department were recruited in
      this prospective study. According to the random number table method, 70 patients
      were divided into three-stitch transverse colostomy group(observation group,
      n=35) and traditional transverse colostomy group(control group, n=35). Procedure
      of three-stitch preventive transverse colostomy was as follows: firstly, at the
      upper 1/3 incision 0.5-1.0 cm distance from the skin, 7# silk was used to suture
      from outside to inside, then the needle belt line went through the transverse
      edge of the mesangial avascular zone. At the lower 1/3 incision 0.5-1.0 cm
      distance from the skin, 7# silk was used to suture from inside to outside, then
      silk went through the transverse edge of the mesangial avascular zone again and
      was ligatured. Finally, in the upper and lower ends of the stoma, 7# silk was
      used to suture and fix transverse seromuscular layer and the skin. The operation
      time and morbidity of postoperative complications associated with colostomy were
      compared between two groups. RESULTS: There were no significant differences in
      baseline data between the two groups(all P>0.05). The operative time of
      observation group was shorter than that of control group [(3.2+/-1.3) min vs.
      (15.5+/-3.4) min, P<0.05]. Incidences of colostomy skin-mucous separation,
      dermatitis, stoma rebound were significantly lower in observation group
      [5.7%(2/35) vs. 34.3%(12/35), P=0.007; 8.6%(3/35) vs. 31.4%(11/35), P=0.036; 0
      vs. 17.1%(6/35), P=0.025, respectively], while incidences of parastomal hernia
      and stoma prolapse in two groups were similar (both P>0.05). CONCLUSION: Compared
      with traditional transverse colostomy method, the three-stitch preventive
      transverse colostomy has more operating advantages and can reduce postoperative
      complications associated with colostomy.

PMID- 28440527
TI  - [Predictive value of combination detection of tissue Pgp1 expression and
      preoperative serum CEA level for colorectal cancer].
AB  - OBJECTIVE: To explore the predictive value of combination detection of Pgp1
      expression in cancer tissue and serum CEA level for the prognosis of colorectal
      cancer (CRC) patients. METHODS: Clinicopathological data, complete 5-year follow
      up data and CRC tissue samples of 153 CRC patients with stage I( to II( tumor
      undergoing radical operation in our department from January 2004 to August 2006
      were retrospectively collected. Immunohistochemical staining was used to detect
      the expression level of Pgp1. The combined evaluation of staining intensity and
      positive cell percentage was performed to determine the expression level of Pgp1.
      Pgp1 staining (-) and (+) was defined as low expression; and staining (++) and
      (+++) as high expression. Electrochemiluminescence immunoassay was used to detect
      the level of serum CEA. CEA > 5 MUg/L was defined as positive. chi2 and Fisher's
      exact test were performed to analyze the association of Pgp1 expression with CEA
      level and clinicopathological variables. Moreover, Kaplan-Meier method was used
      to analyze the survival. Univariate and multivariate Cox proportional hazard
      regression models were used to evaluate the roles of Pgp1 expression combined
      with serum CEA level in prognosis prediction. RESULTS: Of 153 patients, 105 were
      males and 48 females with mean age of 59 (27 to 90) years; 41 cases were rectal
      cancer, and 112 cases colon cancer; 23 patients were TNM stage I( tumor, and 130
      patients stage II( tumor; median follow-up time was 64 months; 30 cases were
      dead. Positive rate of Pgp1 expression in colorectal cancer tissues was
      66.0%(101/153). The expression of Pgp1 was associated with gender, tumor
      location, and survival during the follow-up (all P<0.05). The preoperative
      positive rate of serum CEA was 28.1% (43/153). The preoperative serum CEA level
      was associated with tumor recurrence and survival (all P<0.05). Kaplan-Meier
      analysis showed the overall 5-year survival rate was 81.7%. The 5-year survival
      rate of patients with high expression of Pgp1 was 88.1%, which was significantly
      higher than 69.2% of those with low expression of Pgp1(P=0.003). The 5-year
      survival rate of patients with preoperative positive serum CEA was 72.1%, which
      was significantly lower than 86.1% of those with preoperative negative serum
      CEA(P=0.023). Furthermore, the 5-year survival rate of patients with negative
      Pgp1 plus positive CEA was 66.7%, which was significantly lower than 91.0% of
      those with positive Pgp1 plus negative CEA(P=0.002). Univariate analysis showed
      that gender, Pgp1 expression level, preoperative serum CEA level, and Pgp1
      combined with CEA were significantly associated with the prognosis of
      patients(all P<0.05). Multivariate analysis showed that Pgp1 expression was an
      independent prognostic factor of CRC [HR(95%CI:1.261 to 64.224), P=0.028].
      CONCLUSIONS: Low expression of Pgp1 in cancer tissue indicates poor prognosis in
      patients with stage I( and II( tumor. Combination detection of Pgp1 expression
      and serum CEA can be applied to predict the prognosis of patients with stage I(
      and II( colorectal cancer.

PMID- 28440528
TI  - [Effect of ASCT2 gene knock-down by shRNA on biological behaviors of colorectal
      cancer cells].
AB  - OBJECTIVE: To investigate the effect of ASCT2 gene (glutamine transporter) knock
      down by shRNA on biological behaviors of colorectal cancer cells. METHODS: shRNA
      was transfected into colorectal cancer cells Lovo and SW480 to knockdown ASCT2
      mediated by Lipofectamine 2000. Reverse transcription-PCR and Western blot were
      used to examine the mRNA and protein expression of ASCT2. MTT and transwell assay
      were used to determine the proliferation and invasiveness of Lovo and SW480
      cells. Radioactive-tracer was used to detect the uptake of glutamine. RESULTS:
      ASCT2 mRNA and protein levels were significantly down-regulated by shRNA in Lovo
      and SW480 cells(P<0.01). MTT and transwell assays showed that ASCT2 knock-down
      could significantly inhibit the proliferation of Lovo and SW480 cells (A490) and
      decrease the number of invasive Lovo and SW480 cells from the membrane (both
      P<0.01). The number of membrane Lovo cells in shASCT group and control group was
      46.3+/-5.9 and 197.7+/-9.1, respectively while the number of membrane SW480 cells
      in shASCT group and control group was 29.7+/-3.8 and 139.0+/-9.5, respectively.
      Radioactive-tracer showed that shASCT2 transfection could significantly reduce
      the uptake of glutamine, with an inhibition rate of 79.15% in Lovo and 67.22% in
      SW480 cells (both P<0.01). CONCLUSIONS: ASCT2 plays an oncogenic role in colonic
      cancer, and its promotion mechanism may be associated with glutamine metabolism.
      ASCT2 may be a novel therapeutic target of colonic cancer.

PMID- 28440529
TI  - [Implementation of enhanced recovery after surgery in nutritional management of
      patients undergoing metabolic surgery].
AB  - Metabolic surgery is a gastrointestinal surgical procedure to treat obesity and
      its related co-morbidities with rapid development in recent years. Patients
      undergoing metabolic surgery have preoperative nutritional disorders, and the
      nutrition management for these patients is the key point of perioperative
      management. During the perioperative period, current research has preliminarily
      confirmed that perioperative managements including supplementation of
      micronutrients, preoperative evaluation of the weight loss, preoperative fasting
      and carbohydrate oral intake based on the full application of ERAS and
      characteristics of the patients undergoing metabolic surgery, are safe and
      effective in clinical practice. As for the postoperative diet strategy, current
      literature remains non-unified to identify the duration and the content of the
      nutrition managements. Domestic clinical reports about the postoperative
      nutrition managements after metabolic surgery are rare and lack of unified and
      good reference standard. Meanwhile, divergence still existed in current
      literature regarding to the content of the postoperative nutrition managements.
      Therefore, it is necessary to develop the standardized protocol for nutrition
      managements which is offering basis and reference for the clinical application of
      perioperative nutrition managements after metabolic surgery.

PMID- 28440530
TI  - Comorbidity in patients undergoing surgery for lung cancer. Do we have an
      adequate tool to assess it?
AB  - INTRODUCTION: In the recent years comorbidity has been discussed as a factor
      affecting therapeutic decisions, the course of treatment, and prognosis of
      patients with lung cancer. The aim of the study was 1. to evaluate the occurrence
      of comorbidities in patients with lung cancer undergoing surgery, and 2. to
      investigate the utility of Charlson Comorbidity Index (CCI) and Simplified
      Comorbidity Score (SCS) for preoperative evaluation of Polish patients with lung
      cancer. MATERIAL AND METHODS: The retrospective study included 476 patients with
      lung cancer, who underwent surgical treatment. In all patients, data on
      histopathological type of the tumor, stage, history of smoking, comorbidities,
      and spirometric parameters were collected. CCI and SCS scores were calculated.
      The presence of comorbidities was analyzed in relation to sex, histology, and
      stage of lung cancer. Correlations between CCI and SCS scores and age, number of
      pack-years, spirometric parameters were assessed. RESULTS: The most prevalent
      comorbidities were hypertension (42%), chronic obstructive pulmonary disease
      (COPD) (22%), coronary heart disease (17%), and diabetes (12%). There were no
      differences in the distribution of comorbidity depending on the histological type
      and stage of lung cancer. The CCI and SCS scores showed correlations with age,
      number of pack-years and spirometric parameters, however, their compounds do not
      reflect the profile of most prevalent comoribidities. CONCLUSION: The burden of
      comorbidity among patients with lung cancer is significant. Comorbidity should be
      assessed while considering patients for surgical treatment. However, the CCI and
      SCS do not seem precise enough for this purpose.

PMID- 28440531
TI  - Initial Polish experience of Flexible 19 gauge Endobronchial Ultrasound-Guided
      Transbronchial Needle Aspiration.
AB  - INTRODUCTION: EBUS is a well established minimally invasive diagnostic tool for
      mediastinal and hilar lymphadenopathy. The novel ViziShot Flex 19G needle
      (Olympus Respiratory America, Redmond, WA, USA) was introduced in 2015 in order
      to improve loaded scope flexion and to obtain larger tissue samples for analysis.
      The aims of this study were to assess diagnostic yield of Flex 19G needles and to
      present endoscopist's feedback about the endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA). MATERIAL AND METHODS: The Flex 19G
      needles were used in patients with hilar and/or mediastinal adenopathy in two
      Polish pulmonology centers. Cytology smears and cell blocks (CB) were prepared.
      The prospective analysis was performed due to collected data. RESULTS: Twenty two
      selected patients with confirmed adenopathy on chest-CT (mean age 58 +/- 12)
      underwent EBUS-TBNA with use of Flex 19G needles. All procedures occurred to be
      diagnostic for smears (yield 100%). The malignancy was found in 15 cases (68.2%),
      and benign adenopathy in 7 (31.8%). In 12 of 14 cases of lung cancer (yield
      85.7%) CB were diagnostic for immunohistochemical and molecular staining. After
      puncturing nodes, especially in hilar position not extensive bleeding was
      observed. Comparing to standard 21/22G EBUS-TBNA endoscopists underlined better
      flexion of loaded scope and sample adequacy and found non-significant differences
      in another biopsy details. CONCLUSIONS: The first Polish experience with use of
      Flex 19G EBUS-TBNA needle occurs to be similar in performance with standard
      technique with use of 22/21G needles and presents high diagnostic yield for lung
      cancer diagnostics, especially when preparing CB. A safety profile of the biopsy
      is acceptable.

PMID- 28440532
TI  - The assessment of cancer-related fatigue syndrome in patients with lung cancer
      during palliative chemotherapy.
AB  - INTRODUCTION: Cancer-related fatigue is one of the most common problems of
      patients with lung cancer. The assessment of cancer- -related fatigue is
      therefore a significant medical problem in patients during treatment with
      palliative chemotherapy. MATERIAL AND METHODS: The study included 100 patients
      during palliative chemotherapy because of lung cancer. The study was conducted in
      the Department of Pulmonary Diseases and Treatment of Lung Cancer in the Kuyavian
      and Pomeranian Centre of Pulmonology in Bydgoszcz, in the period from February to
      June 2016. The study used a socio-demographic questionnaire and Cancer Related
      Fatigue scale (CRF) consisting of 22 closed questions. RESULTS: Men accounted for
      68% of the study group, people with vocational education - 61%, and people living
      in the city - 61%. People aged 51-65 formed the largest group. The mean value for
      behavioural fatigue was 5.34 points, the sensory one - 5.44 points,
      cognitive/mood fatigue - 4.29 points (moderate levels), whereas mean value for
      affective fatigue was at a serious level - 5.89 points. The average severity of
      general fatigue was 5.2 points (moderate level of fatigue). CONCLUSIONS: The
      moderate level of cancer-related fatigue occurs in half of patients treated with
      chemotherapy because of lung cancer, and lasts for several months. Behavioural,
      sensory, cognitive/mood and general fatigue have moderate levels but affective
      fatigue has a severe level. Radiation therapy affects the severity of
      cognitive/mood fatigue, lowers economic status, influences behavioural fatigue
      and education level, and has an effect on general fatigue. In multivariate
      analysis, only the reduction of economic status has a significant impact on the
      severity of fatigue. &nbsp.

PMID- 28440533
TI  - Nationwide trends in inpatient admissions of pulmonary hypertension in the United
      States from 2000 to 2013.
AB  - INTRODUCTION: Pulmonary hypertension (PH) is a disorder of the pulmonary
      vasculature with high mortality and bears a large economic burden on the
      healthcare system. We conducted a review of the largest inpatient database in the
      United States and analyzed the trends in hospitalizations due to PH from the turn
      of the century (2000) to 2013 to evaluate the rate of hospitalizations and
      determine the cost and mortality associated with PH. MATERIAL AND METHODS: We
      analyzed the National Inpatient Sample Database (NIS) for all patients in which
      PH (Primary or Secondary) or cor pulmonale was the primary discharge diagnosis
      (ICD-9: 416.0, 416.8 and 416.9) from 2000 to 2013. The NIS is the largest all
      payer inpatient database in the United States and contains data from
      approximately 8 million hospital stays each year. The statistical significance of
      the difference in the number of hospital discharges, lengths of stays and
      associated hospital costs over the study period was calculated. RESULTS: In 2000,
      there were 12,066 hospital admissions with the principal discharge diagnosis of
      pulmonary hypertension, which increased to 13,605 admissions in 2013 (p < 0.001).
      The mean length of stay for PH increased from 5.89 days to 6.67 days during this
      period (p = 0.04). During the same period, the hospital charges increase by
      174.5% from US$ 24,973 in 2000 to US$ 68,545 in 2013 (Adjusted for inflation).
      The aggregate cost of hospital visits of a patient increased by 209.5% from US$
      301,324,218 in 2000 to US$ 932,554,725 in 2013. CONCLUSIONS: The number of
      inpatient discharges related to PH has increased even though the number of
      inpatient discharges with PAH has been reported to be lower in literature. The
      mean length of stay has also shown a mild increase. This increase is associated
      with a significant increase in the mean and aggregate cost. These inpatient costs
      associated with PH contribute significantly to the total healthcare burden.
      Further research on cost-effective evaluation and management of PH is required.

PMID- 28440534
TI  - Searching online for health-related information by people suffering from
      respiratory allergy and asthma: the results of a survey study.
AB  - INTRODUCTION: The objective of the study was to compare online behaviour in
      groups of persons suffering from respiratory allergy and/or asthma and in the
      reference group. MATERIAL AND METHODS: Comparative analysis of two independent
      questionnaire studies. Study A was carried out in the Masovian Voivodeship,
      Poland in 2013. As many as 1,728 questionnaires were collected and 51 respondents
      were selected for analysis (study A, reference group). Study B was carried out in
      2014 in a group of 59 patients of the outpatient allergy clinic. RESULTS: More
      than 92% of the general population (study A) declared that they used the Internet
      to search for health-related information, health protection, while in the group
      of patients (study B) the same was declared by 97%. Both studies showed that more
      than 74% of respondents looked for online information on a specific disease (p >
      0.05). Information on how other persons cope with similar health issues was
      searched by 20% (study A) and 33% (study B) of respondents. Advice on different
      methods of treatment of a given disease was sought by 40% and 51% of respondents,
      respectively. Nearly 51% of respondents in study A and 56% of subjects in study B
      searched online for health information when they did not feel well or were sick.
      CONCLUSIONS: Both in the group of chronically ill persons and in the reference
      group, it is common to search online for health- -related information. Persons
      suffering from respiratory allergy and/or asthma verified the physician's
      diagnosis on the Internet much more often than did the reference group.

PMID- 28440535
TI  - Socioeconomic status and its relationship to chronic respiratory disease.
AB  - Socioeconomic status (SES) is defined as an individual's social or economic
      standing, and is a measure of an individual's or family's social or economic
      position or rank in a social group. It is a composite of several measures
      including income, education, occupation, location of residence or housing.
      Studies have found a lower SES has been linked to disproportionate access to
      health care in many diseases. There is emerging data in pulmonary diseases such
      as COPD, asthma, cystic fibrosis, pulmonary hypertension and other chronic
      respiratory conditions that allude to a similar observation noted in other
      chronic diseases. In the setting of COPD, SES has an inverse relationship with
      COPD prevalence, mortality, health utilization costs and HRQoL. Asthma and cystic
      fibrosis show an increased severity and hospitalizations in relationship to a
      lower SES. Similar observations were seen in sarcoidosis, PHTN and obstructive
      sleep apnea. There remains a limited data on non-CF bronchiectasis and
      interstitial lung diseases. Population SES may be gauged by various measures such
      as education, occupation, marital status but no value is more indicative than
      income. Currently guidelines and management algorithms do not factor the effect
      of SES in the disease process. Despite the great amount of data available, a
      standardized method must be created to include SES in the prognostic calculations
      and management of chronic pulmonary diseases.

PMID- 28440536
TI  - Selected bone morphogenetic proteins - the possibility of their use in the
      diagnostics and therapy of severe asthma.
AB  - Asthma is a chronic heterogeneous illness of the lower airway with an
      inflammatory basis, developing from hyperresponsiveness and bronchial
      obstruction. One of the more unfavourable processes occurring in the airway are
      the long-term changes of the respiratory tract known as remodelling, resulting in
      complete irreversible obstruction. Bone morphogenetic protein (BMP) is a member
      of the Transforming Growth Factor beta (TGF-b) superfamily, which regulates
      processes in embryonic and post-embryonic development. The role played by BMP is
      regulation of degradation and remodelling of the extracellular matrix, which is
      one of the elements involved in the reconstruction of the structure of the
      bronchi in severe asthma. This paper presents the antagonistic properties of BMP
      against TGF-b, anti-inflammatory and counteracting fibrosis in the respiratory
      tract. The current state of knowledge indicates that this group of cytokines are
      potential new markers of remodelling in severe asthma, and further studies on
      their therapeutic value are necessary.

PMID- 28440537
TI  - Speech therapy - a non-pharmacological method to manage difficult-to-treat
      chronic cough.
AB  - Cough is the most common symptom of respiratory diseases. The results of
      management of chronic cough in adults are still unsatisfactory. Unexplained and
      difficult-to-treat chronic cough causes significant impairment in patients'
      quality of life. The results of recent studies suggest that speech therapy
      (speech language intervention) is one of the few methods which are usefull in
      management of persistent chronic cough. We present a case of a patient with
      chronic cough due to chronic nonallergic rhinitis and gastroesophageal reflux
      disease, who had been unsuccessfully treated for 18 years. In the patient speech
      therapy resulted in a significant decrease of cough severity and improvement of
      quality of life.

PMID- 28440538
TI  - Massive nasal polyposis in a patient with newly diagnosed cystic fibrosis.
AB  - INTRODUCTION: Cystic fibrosis (CF) - is the most common fatal autosomal recessive
      disease in Caucasians. A number of reports have described patients who do not
      meet diagnostic criteria for cystic fibrosis. Atypical or nonclassic CF is
      characterised by normal or borderline sweat test, pancreatic sufficiency and a
      monosymptomatic phenotype. For these reasons clinicians should remain alert to
      the possibility of the occurrence of CF. CASE REPORT: We described a case
      presentation of massive nasal polyposis and recurrent sinusitis leading to the
      diagnosis ofcystic fibrosis in a 11-year-old male. CONCLUSION: Our study
      indicates that chronic sinusitis and/or polyposis should raise the clinicians
      suspicion of a potential presentation of undiagnosed CF and require further
      investigations.

PMID- 28440539
TI  - Corticosteroids and hip fracture risk in elderly respiratory patients.

PMID- 28440540
TI  - Corticosteroids and hip fracture risk in elderly respiratory patients: EPIC
      Greece cohort.

PMID- 28440541
TI  - Digests: Plasticity responses help in coping with predation in nature.

PMID- 28440543
TI  - Registered nurses' perceptions regarding nurse-led antiretroviral therapy
      initiation in Hhohho region, Swaziland.
AB  - BACKGROUND: Swaziland has the highest HIV prevalence globally. It faces a
      critical shortage of health workers for addressing the HIV pandemic. To curb this
      human resource challenge, Swaziland adopted a nurse-driven model for
      antiretroviral therapy delivery in line with the recommendations of the World
      Health Organization on task shifting. OBJECTIVE: The study explored the
      perceptions of registered nurses on the nurse-led antiretroviral therapy
      initiation programme in the Hhohho region of Swaziland (NARTIS). DESIGN: The
      study utilized a phenomenological design, specifically a phenomenographic design.
      SETTING: The study was conducted in ten health facilities in the Hhohho region of
      Swaziland. These facilities comprised eight clinics, a hospital and a health
      centre. PARTICIPANTS: These were registered nurses, trained and certified in the
      nurse-led antiretroviral therapy initiation programme. The nurses also had
      experience of working in a nurse-led antiretroviral therapy initiation programme.
      Eighteen (18) nurses were purposively selected and recruited to participate in
      the study. METHODS: Data were collected through open and deep individual
      interviews guided by a semi-structured interview schedule. The audio-recorded
      interviews were transcribed and analysed thematically using Sjostrom and
      Dahlgren's approach to data analysis. RESULTS: Three major themes emerged from
      the study data: nurses' emotional reactions to the implementation of the NARTIS
      programme, and influences and overcoming barriers to the programme. CONCLUSIONS:
      The study findings have generated insights into this program which is useful for
      the provision of care to people living with HIV/AIDS in Swaziland. But nurses
      need support to ensure effective implementation. IMPLICATION FOR NURSING AND
      HEALTH POLICY: The study findings have implications for both the practice of the
      NARTIS programme and health policy development. The development of a health
      policy that alleviates the barriers to the NARTIS programme can enhance nurses'
      role and make care provision to people living with HIV/AIDS more effective.

PMID- 28440542
TI  - Menstrual and reproductive factors and lung cancer risk: A pooled analysis from
      the international lung cancer consortium.
AB  - Many clinical features of lung cancer are different in women and men. Sex steroid
      hormones exert effects in nonreproductive organs, such as the lungs. The
      association between menstrual and childbearing factors and the risk of lung
      cancer among women is still debated. We performed a pooled analysis of eight
      studies contributing to the International Lung Cancer Consortium (4,386 cases and
      4,177 controls). Pooled associations between menstrual or reproductive factors
      and lung cancer were estimated using multivariable unconditional logistic
      regression. Subgroup analyses were done for menopause status, smoking habits and
      histology. We found no strong support for an association of age at menarche and
      at menopause with lung cancer, but peri/postmenopausal women were at higher risk
      compared to premenopausal (OR 1.47, 95% CI 1.11-1.93). Premenopausal women showed
      increased risks associated with parity (OR 1.74, 95% CI 1.03-2.93) and number of
      children (OR 2.88, 95% CI 1.21-6.93 for more than 3 children; p for trend 0.01)
      and decreased with breastfeeding (OR 0.54, 95% CI 0.30-0.98). In contrast,
      peri/postmenopausal subjects had ORs around unity for the same exposures. No
      major effect modification was exerted by smoking status or cancer histology.
      Menstrual and reproductive factors may play a role in the genesis of lung cancer,
      yet the mechanisms are unclear, and smoking remains the most important modifiable
      risk factor. More investigations in large well-designed studies are needed to
      confirm these findings and to clarify the underlying mechanisms of gender
      differences in lung cancer risk.

PMID- 28440545
TI  - Cell reintegration: Stray epithelial cells make their way home.
AB  - Ongoing work shows that misplaced epithelial cells have the capacity to
      reintegrate back into tissue layers. This movement appears to underlie tissue
      stability and may also control aspects of tissue structure. A recent study
      reveals that cell reintegration in at least one tissue, the Drosophila follicular
      epithelium, is based on adhesion molecules that line lateral cell surfaces. In
      this article we will review these observations, discuss their implications for
      epithelial tissue development and maintenance, and identify future directions for
      study.

PMID- 28440544
TI  - Age-related effect of cell death on fiber morphology and number in tongue muscle.
AB  - INTRODUCTION: Multiple pathways may exist for age-related tongue muscle
      degeneration. Cell death is one mechanism contributing to muscle atrophy and
      decreased function. We hypothesized with aging, apoptosis, and apoptotic
      regulators would be increased, and muscle fiber size and number would be reduced
      in extrinsic tongue muscles. METHODS: Cell death indices, expression of caspase-3
      and Bcl-2, and measures of muscle morphology and number were determined in
      extrinsic tongue muscles of young and old rats. RESULTS: Significant increases in
      cell death, caspase-3, and Bcl-2 were observed in all extrinsic tongue muscles
      along with reductions in muscle fiber number in old rats. DISCUSSION: We
      demonstrated that apoptosis indices increase with age in lingual muscles and that
      alterations in apoptotic regulators may be associated with age-related
      degeneration in muscle fiber size and number. These observed apoptotic processes
      may be detrimental to muscle function, and may contribute to degradation of
      cranial functions with age. Muscle Nerve 57: E29-E37, 2018.

PMID- 28440546
TI  - Stem cell dynamics in muscle regeneration: Insights from live imaging in
      different animal models.
AB  - In recent years, live imaging has been adopted to study stem cells in their
      native environment at cellular resolution. In the skeletal muscle field, this has
      led to visualising the initial events of muscle repair in mouse, and the entire
      regenerative response in zebrafish. Here, we review recent discoveries in this
      field obtained from live imaging studies. Tracking of tissue resident stem cells,
      the satellite cells, following injury has captured the morphogenetic dynamics of
      stem/progenitor cells as they facilitate repair. Asymmetric satellite cell
      division generated a clonogenic progenitor pool, providing in vivo validation for
      this mechanism. Furthermore, there is an emerging role of stem/progenitor cell
      guidance at the injury site by cellular protrusions. This review concludes that
      live imaging is a critical tool for discovering the distinct processes that occur
      during regeneration, emphasising the importance of imaging in diverse animal
      models to capture the entire scope of stem cell functions. Also see the Video
      Abstract. Link to: https://youtube/tgUHSBD1N0g.

PMID- 28440547
TI  - Development of LC-QTOF-MS method for human lung tissue fingerprinting. A
      preliminary application to nonsmall cell lung cancer.
AB  - The major histologic subtypes of non-small cell lung cancer (NSCLC) include
      adenocarcinoma (ADC), squamous cell lung carcinoma (SCC), and large-cell
      carcinoma (LCC). Clinical trials of targeted agents and newer chemotherapy agents
      yielded differences in outcomes according to histologic subgroups providing a
      rationale for histology-based treatment in NSCLC. Currently, NSCLC subtyping is
      performed based on histopathological examinations and immunohistochemistry.
      However available methods leave about 10% of NSCLC cases as not otherwise
      specified. The purpose of this study was development of an LC-QTOF-MS method for
      human lung tissue metabolic fingerprinting that could discriminate NSCLC
      histological subtypes and propose biomarkers candidates that could support proper
      NSCLC diagnosis. Metabolites were extracted with acetonitrile or methanol/ethanol
      and different chromatographic conditions were tested. In the final method 10 mg
      of lung tissue was homogenized with 50% methanol and metabolites were extracted
      with acetonitrile. Metabolites were separated on C8-RP and HILIC columns. About
      3500 and 2000 of metabolic features (in both ion modes) were detected with good
      repeatability (CV < 20%) by RP and HILIC methods, respectively. Lung tumor and
      control tissue samples obtained from NSCLC patients were analyzed with developed
      methodology. Acylcarnitines, fatty acids, phospholipids, and amino acids were
      found more abundant in tumor as compared to control tissue. Acylcarnitines,
      lysophospholipids, creatinine, creatine, and alanine were identified as potential
      targets enabling classification of NSCLC subtypes.

PMID- 28440549
TI  - Feel American, Watch American, Eat American? Remote Acculturation, TV, and
      Nutrition Among Adolescent-Mother Dyads in Jamaica.
AB  - Globalization prompts remote acculturation toward U.S. culture in Jamaica; this
      study used a bioecological systems approach to examine its proximal impact on
      nutrition through U.S. cable TV consumption, and maternal influences in the home.
      Overall, 330 randomly selected adolescent-mother dyads from schools in Kingston,
      Jamaica (Madolescent_age  = 13.8 years, SDadolescent_age  = 1.8) completed
      questionnaires reporting American identity and behavioral preferences, daily time
      spent watching U.S.-produced TV programs, and frequency of eating unhealthy
      foods. Actor-partner interdependence models revealed that girls' American
      identity/behavior directly predicted their unhealthy eating, whereas girls'
      mothers and boys' American identity/behavior indirectly predicted unhealthy
      eating as mediated by their U.S. TV hours. Additionally, mothers' American
      identity/behavior predicted daughters' unhealthy eating as mediated by mothers'
      U.S. TV hours. Remote acculturation theory may facilitate more targeted research
      and prevention/intervention.

PMID- 28440550
TI  - Political drivers of epidemic response: foreign healthcare workers and the 2014
      Ebola outbreak.
AB  - This study demonstrates that countries responded quite differently to calls for
      healthcare workers (HCWs) during the Ebola epidemic in West Africa in 2014. Using
      a new dataset on the scale and timing of national pledges and the deployment of
      HCWs to states experiencing outbreaks of the virus disease (principally, Guinea,
      Liberia, and Sierra Leone), it shows that few foreign nations deployed HCWs
      early, some made pledges but then fulfilled them slowly, and most sent no HCWs at
      all. To aid understanding of such national responses, the paper reviews five
      theoretical perspectives that offer potentially competing or complementary
      explanations of foreign government medical assistance for international public
      health emergencies. The study systematically validates that countries varied
      greatly in whether and when they addressed HCW deployment needs during the Ebola
      crisis of 2014, and offers suggestions for a theory-driven inquiry to elucidate
      the logics of foreign interventions in critical infectious disease epidemics.

PMID- 28440548
TI  - Contact sensitizers trigger human CD1-autoreactive T-cell responses.
AB  - Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin
      disease induced by exposure to small molecular-weight haptens, which covalently
      bind to proteins. The abundance of cutaneous T cells that recognize CD1a antigen
      presenting molecules raises the possibility that MHC-independent antigen
      presentation may be relevant in some hapten-driven immune responses. Here we
      examine the ability of contact sensitizers to influence CD1-restricted immunity.
      Exposure of human antigen-presenting cells such as monocyte-derived dendritic
      cells and THP-1 cells to the prototypical contact sensitizer dinitrochlorobenzene
      potentiated the response of CD1a- and CD1d-autoreactive T cells, which released a
      vast array of cytokines in a CD1- and TCR-dependent manner. The potentiating
      effects of dinitrochlorobenzene depended upon newly synthesized CD1 molecules and
      the presence of endogenous stimulatory lipids. Further examination of a broad
      panel of contact sensitizers revealed 1,4-benzoquinone, resorcinol, isoeugenol,
      and cinnamaldehyde to activate the same type of CD1-restricted responses. These
      findings provide a basis for the antigen-specific activation of skin-associated
      CD1-restricted T cells by small molecules and may have implications for contact
      sensitizer-induced inflammatory skin diseases.

PMID- 28440551
TI  - Alternating pH landscapes shape epithelial cancer initiation and progression:
      Focus on pancreatic cancer.
AB  - We present here the hypothesis that the unique microenvironmental pH landscape of
      acid-base transporting epithelia is an important factor in development of
      epithelial cancers, by rendering the epithelial and stromal cells pre-adapted to
      the heterogeneous extracellular pH (pHe ) in the tumor microenvironment. Cells
      residing in organs with net acid-base transporting epithelia such as the
      pancreatic ductal and gastric epithelia are exposed to very different, temporally
      highly variable pHe values apically and basolaterally. This translates into
      spatially and temporally non-uniform intracellular pH (pHi ) patterns. Disturbed
      pHe - and pHi -homeostasis contributes to essentially all hallmarks of cancer.
      Our hypothesis, that the physiological pHe microenvironment in acid-base
      secreting epithelia shapes cancers arising in these tissues, can be tested using
      novel imaging tools. The acidic tumor pHe in turn might be exploited
      therapeutically. Pancreatic cancers are used as our prime example, but we propose
      that this concept is also relevant for other cancers of acid-base transporting
      epithelia.

PMID- 28440552
TI  - Review article: delivering precision oncology in intermediate-stage liver cancer.
AB  - BACKGROUND: Intermediate-stage hepatocellular carcinoma (HCC), for which trans
      arterial chemoembolization (TACE) constitutes the standard of care, is a patient
      subgroup with significant heterogeneity in clinical outcome. Sources of variation
      relate to differences in tumour burden, hepatic reserve, ethnicity and treatment
      modalities. Increasing research efforts have been dedicated to minimise the
      clinical diversity of this patient population and enhance optimal provision of
      treatment. AIM: To comprehensively review the diverse prognostic models that have
      been proposed to refine the prognostic prediction of patients with HCC undergoing
      TACE. RESULTS: A number of prognostic algorithms (HAP, ART, ABCR score and many
      others) have shown potential to address the clinical heterogeneity characterising
      patients with intermediate-stage HCC and facilitate early identification of
      patients with poor prognostic features in whom alternative treatments or best
      supportive care might be more appropriate than TACE. CONCLUSIONS: While an
      improved characterisation of intermediate-stage HCC is a highly important
      clinical aim, current evidence suggests that novel prognostic algorithms in this
      patient population may offer potential benefits but non-negligible challenges in
      the provision of TACE. This review summarises the currently available evidence to
      facilitate the development of precision oncology in intermediate-stage HCC.

PMID- 28440553
TI  - Different location, same results?

PMID- 28440554
TI  - Tolerability of treatment with pirfenidone or nintedanib for pulmonary fibrosis
      in the real world.

PMID- 28440555
TI  - Striated duct adenoma presenting with intra-tumoral hematoma and papillary
      thyroid carcinoma-like histology.
AB  - Striated duct adenoma of the salivary gland is a rare benign tumor characterized
      by unilayered duct epithelium and striations of the tumor cell membranes. To the
      best of our knowledge, only six cases have been reported in the literature. Here
      we report an additional case, which was complicated by an intra-tumoral hematoma
      on clinical presentation and by papillary thyroid carcinoma-like histology on
      intra-operative frozen section diagnosis. An asymptomatic 78-year-old male
      presented with a two-year-history of a painless tumor of the left parotid. An
      intra-tumoral hematoma, which is unusual for a salivary gland tumor, was
      suspected from results of pre-operative radiology. The patient then underwent a
      left parotidectomy. The intra-operative frozen section diagnosis indicated a
      benign tumor, although ectopic papillary thyroid carcinoma was raised as a
      differential diagnosis since the eosinophilic tumor cells occasionally possessed
      nuclear grooves and nuclear pseudo-inclusions. By precise histopathological
      examination using paraffin sections, the tumor was finally diagnosed as striated
      duct adenoma. This type of tumor has unique features of hypervascular stroma and
      papillary thyroid carcinoma-like nuclei. In our case, the former feature was
      associated with the intra-tumoral hematoma and the latter feature, with
      difficulty in frozen section tumor diagnosis.

PMID- 28440556
TI  - Direct hemoperfusion with polymyxin B-immobilized fibre treatment for acute
      exacerbation of interstitial pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Acute exacerbation of idiopathic pulmonary fibrosis (AE
      IPF) is recognized as an important cause of mortality. AE has also been reported
      in patients with other interstitial lung diseases such as idiopathic non-specific
      interstitial pneumonia (NSIP) and interstitial pneumonia associated with collagen
      vascular disease (CVD). Current therapies such as high-dose corticosteroid with
      immunosuppressive agents have provided little benefit for AE. Direct
      hemoperfusion (DHP) with a polymyxin B-immobilized fibre column (PMX) was
      originally developed for the treatment of endotoxaemia. Recent clinical reports
      have suggested beneficial effects of PMX-DHP treatment on patients with AE. In
      this study, we evaluated the effectiveness and safety of PMX-DHP treatment for
      patients with AE. METHODS: The clinical records of patients with AE admitted to
      our intensive care unit between 2006 and 2015 were retrospectively reviewed.
      RESULTS: Of 54 patients with AE identified from clinical records, 24 were treated
      with PMX-DHP and 30 were treated without PMX-DHP. The peripheral white blood cell
      count was significantly decreased (P < 0.001) and the PaO2 /FiO2 (P/F) ratio was
      significantly improved after PMX-DHP (P = 0.032). While no significant difference
      was found in the survival proportion between patients treated with and without
      PMX-DHP, the prognosis of patients with dermatomyositis was significantly
      improved with the treatment (P = 0.045). Among the PMX-DHP-treated patients,
      those who received the treatment within 3 days of AE onset tended to have a
      better prognosis (P = 0.026). CONCLUSION: The early induction of PMX-DHP
      treatment may improve the prognosis of patients with AE, especially those with
      dermatomyositis.

PMID- 28440557
TI  - Implementation of Probabilistic Algorithms by Multi-chromophoric Molecular
      Networks with Application to Multiple Travelling Pathways.
AB  - The implementation of probabilistic algorithms by deterministic hardware is
      demanding and requires hundreds of instructions to generate a pseudo-random
      sequence of numbers. On the contrary, the dynamics at the molecular scale is
      physically governed by probabilistic laws because of the stochastic nature of
      thermally activated and quantum processes. By simulating the exciton transfer
      dynamics in a multi-chromophoric system, we demonstrate the implementation of a
      random walk that samples the possible pathways of a traveler through a network
      and can be probed by time-resolved fluorescence spectroscopy. The ability of
      controlling the spatial arrangement of the chromophores allows us to design the
      "landscape" in which the traveler is moving and therefore to program the
      molecular device.

PMID- 28440558
TI  - What determines organ size differences between species? A meta-analysis of the
      cellular basis.
AB  - Little is known about how the characteristic differences in organ size between
      species are regulated. At the cellular level, the size of an organ is strictly
      regulated by cell division and expansion during its development. We performed a
      meta-analysis of the growth parameters of roots, and Graminae and
      eudicotyledonous leaves, to address the question of how quantitative variation in
      these two processes contributes to size differences across a range of species. We
      extracted or derived cellular parameters from published kinematic growth
      analyses. These data were subjected to linear regression analyses to identify the
      parameters that determine differences in organ growth. Our results demonstrate
      that, across all species and organs, similar conclusions can be made: cell number
      rather than cell size determines the final size of plant organs; cell number is
      determined by meristem size rather than the rate at which cells divide; cells
      that are small when leaving the meristem compensate by expanding for longer;
      mature cell size is primarily determined by the duration of cell expansion. These
      results identify the regulation of the transition from cell division to expansion
      as the key cellular mechanism targeted by the evolution of organ size.

PMID- 28440559
TI  - A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or
      refractory lymphoma.
AB  - Deregulation of histone deacetylase (HDAC) is important in the pathogenesis of
      follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Mocetinostat,
      an isotype-selective HDAC inhibitor, induces accumulation of acetylated histones,
      cell cycle arrest and apoptosis in several cancers. This phase 2 study evaluated
      mocetinostat in patients with relapsed/refractory (R/R) DLBCL and FL. Seventy-two
      patients received mocetinostat (starting doses: 70-110 mg TIW, 4-week cycles).
      The best overall response rate (95% CI) was 18.9% (7.2, 32.2) for the DLBCL
      cohort (n = 41), and 11.5% (1.7, 20.7) for the FL cohort (n = 31). Responses were
      durable (>=90 days in 7 of 10 responses). Overall, 54.1% and 73.1% of patients
      derived clinical benefit (response or stable disease) from mocetinostat in the
      DLBCL and FL cohorts, respectively. Progression-free survival ranged from 1.8 to
      22.8 months and 11.8 to 26.3 months in responders with DLBCL and FL,
      respectively. The most frequent treatment-related adverse events were fatigue
      (75.0%), nausea (69.4%) and diarrhoea (61.1%). Although mocetinostat had limited
      single-agent activity in R/R DLBCL and FL, patients with clinical benefit had
      long-term disease control. The safety profile was acceptable. This drug class
      warrants further investigation, including identifying patients more likely to
      respond to this agent, or in combination with other agents.

PMID- 28440560
TI  - Parental perception of child's body mass index and health within primary care.
AB  - BACKGROUND AND PURPOSE: Overweight and obesity are sensitive issues to address
      with pediatric patients during any visit. Patients and families may not recognize
      that their child is overweight or obese and may not be ready to make change. The
      goals for this study were to collect overall statistics on the clinic in regards
      to weight status of children presenting for well child visits and to capture
      parental perception of the child's weight status in relation to child's age.
      METHODS: A consecutive sample of parents and caregivers with a child aged 2-18
      completed the survey and consented for the study on the day of the survey during
      a well child visit. CONCLUSIONS: Parents, regardless of culture and age tended to
      underestimate the weight of their child. These findings further support the
      literature in that the younger the child, the more likely it is that the parent
      underestimates their weight status. IMPLICATIONS FOR PRACTICE: Interventions
      should include early education with parents on what a healthy weight is and how
      it can predict future health. Addressing and recognizing early concerns and
      assessing parental perception can be important if educational messages are
      delivered throughout the span of the early years.

PMID- 28440562
TI  - The evolvability of herkogamy: Quantifying the evolutionary potential of a
      composite trait.
AB  - Accurate estimates of trait evolvabilities are central to predicting the short
      term evolutionary potential of populations, and hence their ability to adapt to
      changing environments. We quantify and evaluate the evolvability of herkogamy,
      the spatial separation of male and female structures in flowers, a key floral
      trait associated with variation in mating systems. We compiled genetic-variance
      estimates for herkogamy and related floral traits, computed evolvabilities, and
      compared these among trait groups and among species differing in their mating
      systems. When measured in percentage of its own size, the median evolvability of
      herkogamy was an order of magnitude greater than the evolvability of other floral
      size measurements, and was generally not strongly constrained by genetic
      covariance between its components (pistil and stamen lengths). Median
      evolvabilities were similar across mating systems, with only a tendency toward
      reduction in highly selfing taxa. We conclude that herkogamy has the potential to
      evolve rapidly in response to changing environments. This suggests that the
      extensive variation in herkogamy commonly observed among closely related
      populations and species may result from rapid adaptive tracking of fitness optima
      determined by variation in pollinator communities or other selective factors.

PMID- 28440561
TI  - Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case
      report and review of the literature.
AB  - WHAT IS KNOWN AND OBJECTIVES: Rituximab is a chimeric monoclonal anti-CD20
      antibody approved for the treatment of some lymphoid malignancies as well as for
      autoimmune diseases including rheumatoid arthritis (RA), idiopathic
      thrombocytopenic purpura (ITP) and vasculitis. Generally, rituximab is well
      tolerated; nevertheless, some patients develop adverse effects including infusion
      reactions. Albeit rare, these reactions may in some cases be life-threatening
      conditions. Rituximab cardiovascular side effects include more common effects
      such as hypertension, oedema and rare cases of arrhythmias and myocardial
      infarction. CASE SUMMARY: In this article, we report a case of a 58-year-old man
      with a history of overlap syndrome including RA and limited scleroderma who was
      treated with rituximab and developed a dramatic ST-elevation myocardial
      infarction (STEMI) during the drug administration. WHAT IS NEW AND CONCLUSION:
      This report underlines previous published reports emphasizing the awareness of
      such an association. This communication also warrants the importance of screening
      for ischaemic heart disease in selected cases of patients treated with rituximab.

PMID- 28440563
TI  - The small ubiquitin-like modifier E3 ligase MdSIZ1 promotes anthocyanin
      accumulation by sumoylating MdMYB1 under low-temperature conditions in apple.
AB  - MdMYB1 acts as a crucial component of the MYB-bHLH-WD40 complex to regulate
      anthocyanin biosynthesis in red-skinned apples (Malus domestica), but little is
      known about its post-translational regulation. Here, a small ubiquitin-like
      modifier E3 ligase MdSIZ1 was screened out as an MdMYB1-interacting protein with
      a yeast two-hybridization approach. The interaction between MdSIZ1 and MdMYB1 was
      further verified with pull-down and CoIP assays. Furthermore, it was found that
      MdSIZ1 directly sumoylated MdMYB1 proteins in vivo and in vitro, especially under
      moderately low temperature (17  degrees C) conditions, and that this sumoylation
      was required for MdMYB1 protein stability. Moreover, the transcription level of
      MdSIZ1 gene was remarkably induced by low temperature and phosphorus deficiency,
      and MdSIZ1 overexpression exerted a large positive influence on anthocyanin
      accumulation and red fruit coloration, suggesting its important role in the
      regulation of anthocyanin biosynthesis under stress conditions. Our findings
      reveal an important role for a small ubiquitin-like modifier modification of MYB
      transcription factors in regulation of anthocyanin biosynthesis in plants.

PMID- 28440564
TI  - Hypoxia-inhibited DUSP2 expression promotes IL-6/STAT3 signaling in
      endometriosis.
AB  - PROBLEM: How does hypoxia-mediated downregulation of dual-specificity phosphatase
      2 (DUSP2) promote the development of endometriotic lesions? METHOD OF STUDY: The
      levels of IL-6 and DUSP2 were assessed in eutopic stromal cells with DUSP2
      knockdown or hypoxia treatment. Bromodeoxyuridine (BrdU) incorporation was
      applied for evaluating cell proliferation. The protein levels of DUSP2, cleaved
      caspase-3, phosphorylated STAT3, and STAT3 were analyzed using immunoblot.
      RESULTS: The genomewide analysis of cells with DUSP2 overexpression indicated IL
      6 regulates multiple pathways related to inflammation, proliferation, and
      apoptosis. DUSP2 overexpression significantly suppressed IL-6 expression, while
      DUSP2 knockdown promoted IL-6 expression. The hypoxia-treated eutopic stromal
      cells expressed higher levels of IL-6, recapitulating the elevated levels of IL-6
      in ectopic stromal cells. The treatment with IL-6 elicited the phosphorylation of
      STAT3, mimicking the elevated levels of phosphorylated STAT3 in the ectopic
      stromal cells. The IL-6-treated eutopic stromal cells showed more BrdU
      incorporation and less cleaved caspase-3, which can be reversed by STAT3
      inhibitor. CONCLUSION: Hypoxia-induced IL-6 production in endometriotic lesions
      is mediated via downregulation of DUSP2, which causes aberrant activation of
      STAT3 signaling pathway and helps the endometriotic cells survive under the
      ectopic environment.

PMID- 28440565
TI  - Lower limb muscle function and exercise performance in lung cancer.

PMID- 28440566
TI  - C11 /C9 Helical Folding in alphabeta Hybrid Peptides Containing 1-Amino
      cyclohexane acetic acid (beta3, 3 -Ac6 c).
AB  - The present study describes the solid-state conformation of alphabeta hybrid
      peptides, Boc-Leu-beta3, 3 -Ac6 c-OH, P1; Boc-Leu-beta3, 3 -Ac6 c-Leu-beta3, 3 
      Ac6 c-OMe, P2; and Boc-Leu-beta3, 3 -Ac6 c-Leu-beta3, 3 -Ac6 c-Leu-OMe, P3. The
      dipeptide P1 adopts extended conformations, whereas tetrapeptide P2 and
      pentapeptide P3 favor a helical conformation stabilized by mixed types of C11 /C9
      intramolecular hydrogen bonds. In peptide P3, the amino group of beta3, 3 -Ac6
      c(2) and beta3, 3 -Ac6 c(4) residues occupies axial orientation, whereas in P2 it
      occupies axial and equatorial orientations for residues beta3, 3 -Ac6 c(2) and
      beta3, 3 -Ac6 c(4), respectively. The self-assembly of P3 forms channels filled
      with solvent molecules that present interesting patterns.

PMID- 28440567
TI  - Dawson-Type Polyoxomolybdate Anions (P2 Mo18 O626- ) Captured by Ionic Liquid on
      Graphene Oxide as High-Capacity Anode Material for Lithium-Ion Batteries.
AB  - The development of advanced anode materials is of significance for the next
      generation of lithium-ion batteries (LIBs). Herein, imidazolium-based ionic
      liquids (ILs) are grafted covalently on the surface of graphene oxides (GO)
      through the carboxyl-amino bond, providing a loading hotbed for the Dawson-type
      polyoxometalate (POM) of (NH4 )6 P2 Mo18 O62 (denoted as P2 Mo18 ). The as
      prepared GO-IL-P2 Mo18 nanocomposite is characterized by FTIR and Raman
      spectroscopy, TGA, SEM, TEM, and XPS. The nanocomposite is used as the anode
      material for LIBs, and shows a high reversible capacity of 903.9 mAh g-1 with a
      long cycle life over 1000 cycles. Galvanostatic cycling tests, CV measurements,
      and AC impedance spectra reveal that the POMs in the GO-IL-P2 Mo18 nanocomposite
      give an enhanced specific capacity during the Lithium insertion/extraction
      process, and the IL provides a favored contact between the electrolyte and the
      electrode.

PMID- 28440568
TI  - Impact of T wave amplitude in lead aVR on predicting cardiac events in ischemic
      and nonischemic cardiomyopathy patients with an implantable cardioverter
      defibrillator.
AB  - BACKGROUND: T wave amplitudes during ventricular repolarization in the lead aVR
      (TAaVR) are shown to be associated with adverse cardiac events in patients with
      several cardiovascular diseases, such as postmyocardial infarction. However, the
      utility of TAaVR has not been previously evaluated in patients with
      cardiomyopathy who have received implantable cardioverter defibrillators (ICD).
      Patients with ischemic or nonischemic cardiomyopathy (ICM or NICM, respectively)
      and who received an ICD may experience worsening of their condition due to the
      introduction of electric shock during treatment. This study aimed to investigate
      the utility of TAaVR in the prediction of cardiac events in ICM or NICM patients
      with ICD. METHODS: Ninety-three consecutive ICM or NICM patients with ICD were
      retrospectively analyzed (median age: 64 years; male: 77.4%; ICD for secondary
      prevention: 76.3%; NICM: 64.5%). The median follow-up period was 31 months. The
      primary endpoint was defined as composite cardiac events, including cardiac
      death, major ventricular arrhythmic events (MVAE), or hospitalization due to
      heart failure (HHF). RESULTS: Multivariate Cox regression analysis demonstrated
      that less negative TAaVR (-0.1 mV <= TAaVR <0 mV and 0 mV <= TAaVR) was
      independently associated with the primary endpoint (HR: 3.75; 95% confidence
      interval [CI]: 1.09-23.7; p = .04). Kaplan-Meier curve also revealed that the
      event free survival rate in the less negative TAaVR group was significantly lower
      than that in the normal TAaVR group (<-0.1 mV) (p < .01). CONCLUSIONS: TAaVR is
      useful in risk stratification for cardiac events in ICM or NICM patients with
      ICD.

PMID- 28440569
TI  - Toxicity of silver nanoparticles to Arabidopsis: Inhibition of root gravitropism
      by interfering with auxin pathway.
AB  - Impacts of polyvinylpyrrolidine-coated silver nanoparticles (AgNPs) on root
      gravitropism in Arabidopsis thaliana were investigated at the physiological,
      cellular, and molecular levels. Our results showed that AgNPs were taken up by
      the root and primarily localized at the cell wall and intercellular spaces. Root
      gravitropism was inhibited by exposure to AgNPs, and the inhibition in root
      gravitropism caused by exposure to AgNPs exhibited a dose-response relationship.
      Auxin accumulation was reduced in the root tips because of exposure to AgNPs.
      However, increased indole-3-acetic acid level could not rescue the inhibition of
      root gravitropism. Real-time polymerase chain reaction showed significant
      downregulation of expression of auxin receptor-related genes, which is the
      TIR1/AFB family of F-box proteins including AFB1, AFB2, AFB3, AFB5, and TIR1.
      Therefore, the present study suggests that AgNPs have toxicity to the model plant
      A. thaliana as shown by inhibition of root gravitropism along with a reduction in
      auxin accumulation and expression of auxin receptors. Environ Toxicol Chem
      2017;36:2773-2780. (c) 2017 SETAC.

PMID- 28440570
TI  - Mass spectrometric characterization of the selective androgen receptor modulator
      (SARM) YK-11 for doping control purposes.
AB  - RATIONALE: Selective androgen receptor modulators (SARMs) represent an emerging
      class of therapeutics targeting inter alia conditions referred to as cachexia and
      sarcopenia. Due to their anabolic properties, the use of SARMs is prohibited in
      sports as regulated by the World Anti-Doping Agency (WADA), and doping control
      laboratories test for these anabolic agents in blood and urine. In order to
      accomplish and maintain comprehensive test methods, the characterization of new
      drug candidates is critical for efficient sports drug testing. Hence, in the
      present study the mass spectrometric properties of the SARM YK-11 were
      investigated. METHODS: YK-11 was synthesized according to literature data and
      three different stable-isotope-labeled analogs were prepared to support the mass
      spectrometric studies. Using high-resolution/high-accuracy mass spectrometry
      following electrospray ionization as well as electron ionization, the
      dissociation pathways of YK-11 were investigated, and characteristic features of
      its (product ion) mass spectra were elucidated. These studies were flanked by
      density functional theory (DFT) computation providing information on proton
      affinities of selected functional groups of the analyte. RESULTS AND CONCLUSIONS:
      The steroidal SARM YK-11 was found to readily protonate under ESI conditions
      followed by substantial in-source dissociation processes eliminating methanol,
      acetic acid methyl ester, and/or ketene. DFT computation yielded energetically
      favored structures of the protonated species resulting from the aforementioned
      elimination processes particularly following protonation of the steroidal D-ring
      substituent. Underlying dissociation pathways were suggested, supported by stable
      isotope labeling of the analyte, and diagnostic product ions for the steroidal
      nucleus and the D-ring substituent were identified. Further, trimethylsilylated
      YK-11 and its deuterated analogs were subjected to electron ionization high
      resolution/high-accuracy mass spectrometry, complementing the dataset
      characterizing this new SARM. The obtained fragment ions resulted primarily from
      A/B- and C/D-ring structures of the steroidal nucleus, thus supporting future
      studies e.g. concerning metabolic pathways of the substance. Copyright (c) 2017
      John Wiley & Sons, Ltd.

PMID- 28440572
TI  - Feasibility of a multidisciplinary intervention to help cancer patients return to
      work.
AB  - This study evaluates feasibility of a multidisciplinary intervention combining
      occupational counselling with physical exercise to enhance cancer patients'
      return to work, assesses whether care providers and patients were satisfied with
      the intervention, and describes barriers to and facilitators of execution. Newly
      diagnosed cancer patients, treated with chemotherapy and on sick leave from (self
      )employment participated. Patients received counselling from an oncological
      occupational physician (OOP), were assessed by a sports physician, and performed
      a 12-week training programme supervised by physiotherapists. Care providers
      completed registration forms to collect data on reach, dose delivered and
      received in executing the protocol and were interviewed about their satisfaction
      and barriers to and facilitators of execution. Patients completed three
      questionnaires on satisfaction and usefulness of the intervention. Fifty-six per
      cent of all patients were eligible (reach). In total, 123 patients participated.
      For all intervention components dose delivered exceeded 75%; dose received ranged
      from 49%-79%. Overall, patients and care providers were satisfied and perceived
      the intervention as useful. Care providers considered the intervention feasible,
      while execution was facilitated by highly motivated patients and impeded by
      physical limitations hindering exercise. It is feasible to conduct this
      multidisciplinary intervention in cancer patients during curative treatment.
      Patients and care providers were satisfied with the intervention.

PMID- 28440573
TI  - Glycated albumin is stable in plasma when exposed to common laboratory conditions
      and comparable when drawn from venous or capillary sites.
AB  - BACKGROUND: Circulating glycated albumin is a marker of blood glucose reflecting
      the previous 2 weeks. However, the effects of storage conditions and draw site on
      glycated albumin values are not fully understood. METHODS: Fifteen plasma samples
      from people with type 2 diabetes were assessed during repeated freeze-thaw rounds
      for 10 cycles. A further 15 samples were stored at 4 degrees C and assessed over
      3 days. Another 40 samples drawn concurrently from capillary and venous sites had
      their glycated albumin content compared. RESULTS: Glycated albumin concentration
      did not alter over 10 freeze-thaw cycles (P=.856), or after 72 hours at 4 degrees
      C (P=.962). Capillary and venous samples did not differ in their percentage of
      glycated albumin (P=.379), although lower concentrations of albumin and glycated
      albumin (g/dL) were observed in the capillary sample (P<.001). CONCLUSION:
      Glycated albumin in plasma appears relatively stable when exposed to common
      laboratory conditions, reducing a potential confounder to its use as a marker of
      blood glucose control. The glycated albumin (%) in samples from capillary and
      venous sites was comparable, suggesting the potential of rapid or portable
      assessment devices that require a finger prick.

PMID- 28440574
TI  - A worldview of root traits: the influence of ancestry, growth form, climate and
      mycorrhizal association on the functional trait variation of fine-root tissues in
      seed plants.
AB  - Fine-root traits play key roles in ecosystem processes, but the drivers of fine
      root trait diversity remain poorly understood. The plant economic spectrum (PES)
      hypothesis predicts that leaf and root traits evolved in coordination.
      Mycorrhizal association type, plant growth form and climate may also affect root
      traits. However, the extent to which these controls are confounded with
      phylogenetic structuring remains unclear. Here we compiled information about root
      and leaf traits for > 600 species. Using phylogenetic relatedness, climatic
      ranges, growth form and mycorrhizal associations, we quantified the importance of
      these factors in the global distribution of fine-root traits. Phylogenetic
      structuring accounts for most of the variation for all traits excepting root
      tissue density, with root diameter and nitrogen concentration showing the
      strongest phylogenetic signal and specific root length showing intermediate
      values. Climate was the second most important factor, whereas mycorrhizal type
      had little effect. Substantial trait coordination occurred between leaves and
      roots, but the strength varied between growth forms and clades. Our analyses
      provide evidence that the integration of roots and leaves in the PES requires
      better accounting of the variation in traits across phylogenetic clades.
      Inclusion of phylogenetic information provides a powerful framework for
      predictions of belowground functional traits at global scales.

PMID- 28440575
TI  - Divergent Total Syntheses of (-)-Huperzine Q, (+)-Lycopladine B, (+)-Lycopladine
      C, and (-)-4-epi-Lycopladine D.
AB  - We report herein our synthetic efforts towards the divergent syntheses of (-)
      huperzine Q (1), (+)-lycopladine B (2), (+)-lycopladine C (3), and (-)
      lycopladine D (4). The 10-step total synthesis of (-)-huperzine Q (1) and the
      first total syntheses of (+)-lycopladines B (2) and C (3) were accomplished
      through a series of cascade reactions. Our approach involved a Michael
      addition/aldol/intramolecular C-alkylation sequence to forge the 6/9 spirocycle
      ring, and this was followed by an ethylene-accelerated carbonyl-olefin metathesis
      to construct the common 6/5/9 ring system. Finally, late-stage enamine
      bromofunctionalization enabled us to access (-)-huperzine Q (1), (+)-lycopladine
      B (2), and (+)-lycopladine C (3), and a tandem C4-epimerization/retro-Claisen
      condensation furnished (-)-4-epi-lycopladine D (63).

PMID- 28440576
TI  - New cascarosides from Rhamnus purshiana and fragmentation studies of the class by
      ion trap mass spectrometry.
AB  - RATIONALE: Anthrone and oxanthrone are important anthraquinone derivatives
      present in medicinal plants which are used in therapeutics as laxatives. Some of
      these plants need to be stored at least one year before they can be used in order
      to oxidize anthrones into oxanthrones, so to avoid severe diarrhea and
      dehydration. Therefore, this work aimed to characterize fragmentation reactions
      between these anthraquinones to provide an easy way to differentiate between the
      two classes, since it is necessary and important to discriminate and identify
      these derivatives in laxative plants and phytotherapic drugs. METHODS: Anthrone
      (cascarosides A-D) and oxanthrone (10-hydroxycascaroside A and B) derivatives
      were isolated and identified by NMR (1 H, 13 C, DEPT, NOESY) and used for
      fragmentation study by direct infusion on an electrospray ionization (ESI) ion
      trap mass spectrometer (AmazonSL, Bruker) in positive and negative mode. RESULTS:
      The additional hydroxyl at C-10 in oxanthrones allowed McLafferty-type
      rearrangements to form the quinone group in positive mode, while in negative mode
      the second sugar loss infringed the odd-electron rule and formed a radical
      fragment. No differences in fragmentation reactions were found between
      diastereoisomeric pairs, although the additional oxygen at C-10 of oxanthrones
      allowed a different fragmentation pattern. CONCLUSIONS: The proposed
      fragmentation patterns can be used to differentiate anthrones from oxanthrones in
      both ion modes. In addition, they can be applied to differentiate these compounds
      in anthraquinone-rich plants and phytotherapic drugs. Finally, herein, the
      strategy applied allowed us to identify new natural products. Copyright (c) 2017
      John Wiley & Sons, Ltd.

PMID- 28440577
TI  - Variable developmental delays and characteristic facial features-A novel
      7p22.3p22.2 microdeletion syndrome?
AB  - Isolated 7p22.3p22.2 deletions are rarely described with only two reports in the
      literature. Most other reported cases either involve a much larger region of the
      7p arm or have an additional copy number variation. Here, we report five patients
      with overlapping microdeletions at 7p22.3p22.2. The patients presented with
      variable developmental delays, exhibiting relative weaknesses in expressive
      language skills and relative strengths in gross, and fine motor skills. The most
      consistent facial features seen in these patients included a broad nasal root, a
      prominent forehead a prominent glabella and arched eyebrows. Additional variable
      features amongst the patients included microcephaly, metopic ridging or
      craniosynostosis, cleft palate, cardiac defects, and mild hypotonia. Although the
      patients' deletions varied in size, there was a 0.47 Mb region of overlap which
      contained 7 OMIM genes: EIP3B, CHST12, LFNG, BRAT1, TTYH3, AMZ1, and GNA12. We
      propose that monosomy of this region represents a novel microdeletion syndrome.
      We recommend that individuals with 7p22.3p22.2 deletions should receive a
      developmental assessment and a thorough cardiac exam, with consideration of an
      echocardiogram, as part of their initial evaluation.

PMID- 28440578
TI  - Developing social marketed individual preconception care consultations: Which
      consumer preferences should it meet?
AB  - AIMS: Preconception care (PCC) is care that aims to improve the health of
      offspring by addressing risk factors in the pre-pregnancy period. Consultations
      are recognized as a method to promote perinatal health. However, prospective
      parents underutilize PCC services. Uptake can improve if delivery approaches
      satisfy consumer preferences. Aim of this study was to identify preferences of
      women (consumers) as a first step to social marketed individual PCC
      consultations. METHODS: In depth, semi-structured interviews were performed to
      identify women's views regarding the four components of the social marketing
      model: product (individual PCC consultation), place (setting), promotion (how
      women are made aware of the product) and price (costs). Participants were
      recruited from general practices and a midwife's practice. Content analysis was
      performed by systematic coding with NVIVO software. RESULTS: The 39 participants
      reflected a multiethnic intermediately educated population. Product: Many
      participants had little knowledge of the need and the benefits of the product.
      Regarding the content of PCC, they wish to address fertility concerns and social
      aspects of parenthood. PCC was seen as an informing and coaching service with a
      predominant role for health-care professionals. PLACE: the general practitioner
      and midwife setting was the most mentioned setting. Promotion: A professional led
      promotion approach was preferred. Price: Introduction of a fee for PCC
      consultations will make people reconsider their need for a consultation and could
      exclude vulnerable patients from utilization. CONCLUSION: This study provides
      consumer orientated data to design a social marketed delivery approach for
      individual PCC consultations.

PMID- 28440579
TI  - Prevalence of herpes simplex virus types 1 and 2 at maternal and fetal sides of
      the placenta in asymptomatic pregnant women.
AB  - PROBLEM: Herpes simplex virus 1 (HSV-1) commonly causes orolabial infection, but
      can also infect the genital mucosa. In contrast, HSV-2 is usually genital.
      Genital herpes can transmit the virus vertically to the fetus during pregnancy.
      We sought to estimate the prevalence of HSV-1/2 on the maternal and fetal sides
      of the placenta. METHOD OF STUDY: Placental tissues were collected from pregnant
      women seen at the Rio Grande University Hospital. HSV-1 and HSV-2 were detected
      by nested PCR. RESULTS: The prevalence of HSV-1 and HSV-2 was, respectively, 28%
      and 12.6% (maternal side) and 29.9% and 8.3% (fetal side). All HSV-positive women
      were asymptomatic. Sexual behavior, vaginal delivery, and presence of HSVs on one
      side of the placenta were risk factors associated with HSV infection. CONCLUSION:
      The occurrence of HSVs in placental tissue was high, especially for HSV-1. Novel
      strategies need to be implemented for the management of asymptomatic women who
      might transmit HSV to their newborns.

PMID- 28440580
TI  - Systematic review: quality of trials on the symptomatic effects of the low FODMAP
      diet for irritable bowel syndrome.
AB  - BACKGROUND: The low Fermentable Oligo-, Di- Monosaccharides, and Polyoles
      (FODMAP) diet is a new treatment option for irritable bowel syndrome (IBS).
      Experts refer to the diet as supported by high level of evidence, but an
      evaluation of the quality of trials is lacking. AIM: To provide a systematic
      review of the quality of trials on the symptomatic effects of the low FODMAP diet
      for IBS. METHODS: Pubmed and EMBASE were searched for randomised controlled
      trials (RCTs) reporting effect of the low FODMAP diet on IBS symptoms. The
      quality of trials was evaluated by estimating risk of bias and assessing trial
      methodology. RESULTS: Nine RCTs were eligible, including 542 patients. The
      intervention period was from 2 days to 6 weeks and one trial included a 6-month
      follow-up. Three trials intervened by providing meals, controlling with a diet
      high in FODMAP content. In six trials, the intervention was instruction by a
      dietician and a variety of control interventions were used, all with limited
      established efficacy. Domains with a high risk of bias were identified for all
      the trials. High risk of bias dominated domains regarding blinding, with only one
      trial double-blinded. CONCLUSIONS: The RCTs on the low FODMAP diet are
      characterized by high risk of bias. The diet has not been studied in a
      randomised, controlled setting for more than 6 weeks and trials examining the
      effect of the important reintroduction period are lacking. There is a risk that
      the symptomatic effects reported in the trials are driven primarily by a placebo
      response.

PMID- 28440581
TI  - The toxicity of silver to soil organisms exposed to silver nanoparticles and
      silver nitrate in biosolids-amended field soil.
AB  - The use of engineered silver nanoparticles (AgNPs) is widespread, with expected
      release to the terrestrial environment through the application of biosolids onto
      agricultural lands. The toxicity of AgNPs and silver nitrate (AgNO3 ; as ionic
      Ag+ ) to plant (Elymus lanceolatus and Trifolium pratense) and soil invertebrate
      (Eisenia andrei and Folsomia candida) species was assessed using Ag-amended
      biosolids applied to a natural sandy loam soil. Bioavailable Ag+ in soil samples
      was estimated using an ion-exchange technique applied to KNO3 soil extracts,
      whereas exposure to dispersible AgNPs was verified by single-particle inductively
      coupled plasma-mass spectrometry and transmission electron microscopy-energy
      dispersive X-ray spectroscopy analysis. Greater toxicity to plant growth and
      earthworm reproduction was observed in AgNP exposures relative to those of AgNO3
      , whereas no difference in toxicity was observed for F. candida reproduction.
      Transformation products in the AgNP-biosolids exposures resulted in larger pools
      of extractable Ag+ than those from AgNO3 -biosolids exposures, at similar total
      Ag soil concentrations. The results of the present study reveal intrinsic
      differences in the behavior and bioavailability of the 2 different forms of Ag
      within the biosolids-soils pathway. The present study demonstrates how analytical
      methods that target biologically relevant fractions can be used to advance the
      understanding of AgNP behavior and toxicity in terrestrial environments. Environ
      Toxicol Chem 2017;36:2756-2765. (c) 2017 Crown in the Right of Canada. Published
      Wiley Periodicals Inc., on behalf of SETAC.

PMID- 28440582
TI  - PHYTOCHROME INTERACTING FACTORS mediate metabolic control of the circadian system
      in Arabidopsis.
AB  - The circadian (c. 24 h) system has a central role in regulating the timing and
      coordination of photosynthesis, and in turn photosynthesis and photosynthetic
      products which are controlled by the circadian clock feedback to affect the
      circadian oscillator that generates rhythms. However, little is known about the
      mechanism(s) by which this feedback occurs. One group of likely candidates for
      signal transduction to the circadian clock are the PHYTOCHROME INTERACTING FACTOR
      (PIF) family of transcription factors which have been shown to be involved in
      numerous signaling pathways in Arabidopsis. Yet despite evidence that some PIF
      genes are under circadian control and bind promoter motifs present in circadian
      genes, until now PIFs have not been shown to affect the circadian system. Using a
      range of techniques, we have examined how circadian rhythms are affected in
      higher order pif mutants and the mechanisms by which PIFs regulate signaling to
      the circadian clock. We show that PIFs mediate metabolic signals to the circadian
      oscillator and that sucrose directly affects PIF binding to the promoters of key
      circadian oscillator genes in vivo that may entrain the oscillator. Our results
      provide a basis for understanding the mechanism for metabolic signaling to the
      circadian system in Arabidopsis.

PMID- 28440584
TI  - Flood risk and inequalities between ethnic groups in the floodplains of England
      and Wales.
AB  - Previous research has shown that many vulnerable communities experience
      disproportional exposure to flood risk. This paper, though, is the first to look
      at broad ethnic/racial group differences in the United Kingdom. It contends that
      differences in culture and language, especially those of new immigrants, bestow
      vulnerabilities on such communities, resulting in a lack of knowledge that
      enables people to be aware, to be prepared, or to recover expediently after a
      flood emergency. Using UK 2011 Census data and Environment Agency flood maps, the
      paper demonstrates that it is the non-white communities in Wales that confront
      the most disproportionate level of flood risk: 23 per cent as compared to 11.4
      per cent of their white neighbours. In contrast, the difference in flood risk
      between white and non-white ethnic/racial groups in regions of England is within
      a range of plus or minus two per cent, except for in Yorkshire and The Humber
      where white populations face a much greater risk of flooding.

PMID- 28440583
TI  - Topical antibiotics and intravitreal injections.
AB  - There is increasing evidence that topical antibiotics, given before and/or after
      intravitreal injections, are ineffective in preventing endophthalmitis and are
      possibly harmful. In addition to the lack of efficacy and increased development
      of resistant organisms, the use of topical antibiotics adds significantly to the
      cost of delivering intravitreal therapy. Despite this, in many countries, it is
      still common practice to use pre- and/or postinjection topical antibiotics. This
      review outlines the general principles of effective antibiotic prophylaxis, and
      the evidence regarding topical antibiotic use as a prophylactic measure for
      endophthalmitis following intravitreal injections. A key distinguishing feature
      of intravitreal injections from most other invasive procedures is the fact that
      they are often repeated on multiple occasions to the same eye. Given the lack of
      evidence to support topical antibiotics as an effective method of prophylaxis for
      postinjection endophthalmitis, it appears that more widespread education of
      ophthalmologists is required to avoid continued inappropriate use. Revision of
      drug labels in some jurisdictions, and amendment of local/professional society
      guidelines, may be required to assist in achieving this goal. Emphasis should be
      placed on antisepsis and aseptic technique, which are the major proven methods of
      endophthalmitis prevention, rather than antibiotics.

PMID- 28440585
TI  - Is obesity related to postexercise cardiac autonomic recovery?

PMID- 28440587
TI  - Risk-benefit perception of pregnancy among breast cancer survivors.
AB  - Helping breast cancer patients who desire a pregnancy after cancer treatment is a
      vital issue. Little is known about the complex context of the decision to become
      pregnant after breast cancer treatment. The purpose of this study was to
      understand the risk-benefit perception of choosing conception or contraception
      after treatment in Taiwan. We applied grounded theory to guide this exploratory
      qualitative study. Data were collected through in-depth interviews with 16 breast
      cancer patients. Pregnancy was addressed in the context of cancer as a
      potentially life-threatening diagnosis and its treatment. The verbatim
      transcriptions were analysed using constant comparative analysis and methods of
      open, axial and selective coding. The core theme that described the risk
      perception of pregnancy among patients with breast cancer after treatment focused
      on "reaching the balance of life." Seven dimensions of risk-benefit perception of
      pregnancy, including perceived health status, safety, expected gain, harm,
      loading, support and time were explored among women treated for breast cancer. We
      found that women treated for breast cancer applied risk-benefit perceptions to
      decide whether to become pregnant. Implementing contextual counselling could help
      to decrease perceived barriers to choose pregnancy and increase the quality of
      pregnancy care.

PMID- 28440586
TI  - Comparison of Preoperative Quantitative Magnetic Resonance Imaging and Clinical
      Assessment of Deep Pain Perception as Prognostic Tools for Early Recovery of
      Motor Function in Paraplegic Dogs with Intervertebral Disk Herniations.
AB  - BACKGROUND: Prognostic tools to predict early postoperative motor function
      recovery (MFR) after thoracolumbar intervertebral disk herniation (IVDH) in
      paraplegic dogs represent an opportunity to timely implement novel therapies that
      could shorten recovery times and diminish permanent neurological dysfunctions.
      HYPOTHESIS: Fractional anisotropy (FA) values obtained using diffusion tensor
      imaging have a higher prognostic value than a lesion extension ratio in T2
      weighted images (T2W-LER) and clinical assessment of deep pain perception (DPP)
      for MFR. ANIMALS: Thirty-five paraplegic dogs with diagnosis of acute or subacute
      thoracolumbar IVDH. METHODS: Prospective, descriptive observational study. At
      admission, absence or presence of DPP, T2W-LER, and FA values was evaluated. MFR
      was assessed within 4 weeks after decompressive surgery. Values of T2W-LER and FA
      of dogs with and without MFR were compared using t-tests. All 3 methods were
      evaluated for their sensitivity and specificity as a prognostic factor. RESULTS:
      No differences were found between groups regarding T2W-LER. FA values differed
      statistically when measured caudally of lesion epicenter being higher in dogs
      without MFR compared to dogs with MFR (P = .023). Logistic regression analysis
      revealed significance in FA values measured caudally of the lesion epicenter (P =
      .033, area under the curve = 0.72). Using a cutoff value of FA = 0.660, the
      technique had a sensitivity of 80% and a specificity of 55%. Evaluation of DPP
      had a sensitivity of 73.3% and specificity of 75% (P = .007). CONCLUSIONS AND
      CLINICAL IMPORTANCE: Evaluation of DPP showed a similar sensitivity and a better
      specificity predicting early MFR than quantitative magnetic resonance imaging.

PMID- 28440588
TI  - Endometrial immune markers are potential predictors of normal fertility and
      pregnancy after in vitro fertilization.
AB  - PROBLEM: Elucidating immune mechanisms in the endometrium, which lead to the
      success of implantation and pregnancy, is important in reproductive medicine.
      Studies of immune cell abundance have shown conflicting results, and the
      expression and importance of HLA class Ib proteins in pre-implantation
      endometrium have not yet been investigated. METHOD OF STUDY: The study population
      consisted of four subgroups: a hydrosalpinx, a salpingectomy, an unexplained
      infertility, and a fertile control group. Endometrial samples were collected
      during the implantation window. Immune markers (CD56+ and CD16+ cells, FoxP3+
      Tregs, HLA-G, HLA-F) were quantified in the samples. The outcome of the
      subsequent IVF treatment was recorded. RESULTS: Increased CD56+ uNK cells and
      high HLA-G expression served as predictor for successful pregnancy outcome. HLA-F
      expression was positively correlated with uNK cells, being indirectly predictive
      for achieving pregnancy. CONCLUSION: Endometrial uNK cell abundance in the pre
      implantation endometrium seems to be important for normal fertility and pregnancy
      success, and they may be used as clinical markers to predict implantation success
      in IVF.

PMID- 28440589
TI  - Prime movers: Advanced practice professionals in the role of stroke coordinator.
AB  - BACKGROUND AND PURPOSE: Following a stroke quality improvement clustered
      randomized trial and a national acute ischemic stroke (AIS) directive in the
      Veterans Health Administration in 2011, this comparative case study examined the
      role of advanced practice professionals (APPs) in quality improvement activities
      among stroke teams. METHODS: Semistructured interviews were conducted at 11
      Veterans Affairs medical centers annually over a 3-year period. A
      multidisciplinary team analyzed interviews from clinical providers through a
      mixed-methods, data matrix approach linking APPs (nurse practitioners and
      physician assistants) with Consolidated Framework for Implementation Research
      constructs and a group organization measure. CONCLUSION: Five of 11 facilities
      independently chose to staff stroke coordinator positions with APPs. Analysis
      indicated that APPs emerged as boundary spanners across services and disciplines
      who played an important role in coordinating evidence-based, facility-level
      approaches to AIS care. The presence of APPs was related to engaging in group
      based evaluation of performance data, implementing stroke protocols, monitoring
      care through data audit, convening interprofessional meetings involving planning
      activities, and providing direct care. IMPLICATIONS FOR PRACTICE: The presence of
      APPs appears to be an influential feature of local context crucial in developing
      an advanced, facility-wide approach to stroke care because of their boundary
      spanning capabilities.

PMID- 28440591
TI  - Imaging collector channel entrance with a new intraocular micro-probe swept
      source optical coherence tomography.
AB  - PURPOSE: To describe the use of a newly developed side-viewing catheter probe to
      provide the cross-sectional images of collector channel entrance (CCE), achieved
      by swept-source optical coherence tomography (SS-OCT). METHODS: A side-viewing SS
      OCT catheter probe was developed that has a core probe diameter of 0.15 mm and an
      outer diameter of 0.25 mm, for the purpose of imaging CCEs within eye globe.
      Cadaver eyes harvested from swine and human were used to demonstrate its
      feasibility. For porcine eyes, the probe imaged the CCE by accessing the region
      of the aqueous plexus (AP) as well as along the inner wall (IW) of the trabecular
      meshwork (TM). For human eyes, the CCE images were captured by placing the probe
      within the lumen of the Schlemm's canal (SC) and along its IW. RESULTS: With the
      optical coherence tomography (OCT) catheter probe, the CCE is well delineated as
      optically empty areas within the highly scattering sclera. In porcine eyes,
      images captured in the region of the AP demonstrate a large cavity with delicate
      tissue strands around the probe. The CCE can be identified at the outer margin of
      the AP. When imaged along the IW, the TM is discernable but difficult to be
      distinguished from the AP. In the human limbal regions, when placed within the
      lumen of the SC, the catheter probe fully occupies the potential space. TM is
      highly compact. The CCE can be identified at the outer wall of the SC. When
      imaged along the IW of TM, the SC and CCE can be identified. CONCLUSION: The
      intraocular SS-OCT catheter probe is feasible to provide the CCE images,
      indicating useful clinical applications to assist glaucoma surgery.

PMID- 28440590
TI  - Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients
      with type 2 diabetes mellitus: A meta-analysis.
AB  - BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors could potentially
      alter calcium and phosphate homeostasis and may increase the risk of bone
      fracture. METHODS: The current meta-analysis was conducted to investigate the
      fracture risk among patients with type 2 diabetes mellitus treated with SGLT2
      inhibitors. Randomized controlled trials that compared the efficacy of SGLT2
      inhibitors to placebo were identified. The risk ratios of fracture among patients
      who received SGLT2 inhibitors versus placebo were extracted from each study.
      Pooled risk ratios and 95% confidence intervals were calculated using a random
      effect, Mantel-Haenszel analysis. RESULTS: A total of 20 studies with 8286
      patients treated with SGLT2 inhibitors were included. The pooled risk ratio of
      bone fracture in patients receiving SGLT2 inhibitors versus placebo was 0.67 (95%
      confidence interval, 0.42-1.07). The pooled risk ratio for canagliflozin,
      dapagliflozin, and empagliflozin was 0.66 (95% confidence interval, 0.37-1.19),
      0.84 (95% confidence interval, 0.22-3.18), and 0.57 (95% confidence interval,
      0.20-1.59), respectively. CONCLUSIONS: Increased risk of bone fracture among
      patients with type 2 diabetes mellitus treated with SGLT2 inhibitors compared
      with placebo was not observed in this meta-analysis. However, the results were
      limited by short duration of treatment/follow-up and low incidence of the event
      of interest.

PMID- 28440592
TI  - Sequential Reactions of Alkynes on an Iridium(III) Single Site.
AB  - Sequential insertion of terminal alkynes on IrIII cyclometalated complexes allow
      the formation of novel metallapolycycles in a controlled and efficient manner.
      ortho-Methylarylethynyl derivatives led to an unprecedented cascade combination
      of three fundamental processes (C-C bond formation, C(sp3 )-H activation, and
      reductive coupling) on a single IrIII center, in a process compatible with
      functionalized biomolecules and photoactive substrates. The reaction with tert
      butylacetylene led to a [6,5,4]-polycycle that incorporates an
      iridacyclobutenylidene in its structure. The sequence is a multicomponent
      reaction in which the metal not only promotes the different steps but also
      determines their stereoselectivity. This is an elegant example of the synergy
      between a metal-promoting reaction and a symmetry-defined stereochemistry.

PMID- 28440593
TI  - Single-Domain Ferromagnet of Noncentrosymmetric Uniaxial Magnetic Ions and
      Magnetoelectric Interaction.
AB  - The feasibility of a single-domain ferromagnet based on uniaxial magnetic ions
      was examined. For a noncentrosymmetric uniaxial magnetic ion of magnetic moment
      MU at a site of local electric dipole moment p, it is unknown to date whether MU
      prefers to be parallel or antiparallel to MU. The nature of this magnetoelectric
      interaction was probed in terms of analogical reasoning based on the Rashba
      effect and density functional theory (DFT) calculations. We show that MU and p
      prefer an antiparallel arrangement, predict that Fe-doped CaZnOS is a single
      domain ferromagnet like a bar magnet, and find the probable cause for the
      ferromagnetism and weak magnetization hysteresis in Fe-doped hexagonal ZnO and
      ZnS at very low dopant concentrations.

PMID- 28440594
TI  - Identification of a hypertrehalosemic factor in Spodoptera exigua.
AB  - Trehalose is a major blood sugar in insects with a range of physiological
      functions, including an energy source and a cryoprotectant. Hemolymph trehalose
      concentrations are tightly regulated according to physiological conditions. An
      insulin-like peptide, SeILP1, downregulates hemolymph trehalose concentrations in
      Spodoptera exigua. Here, we identified a factor that upregulates hemolymph
      trehalose concentration in S. exigua. Hemolymph trehalose concentrations were
      significantly increased after immune challenge or under starvation in a time
      dependent manner. To determine endocrine factors responsible for the
      upregulation, stress-associated mediators, such as octopamine, serotonin, or
      eicosanoids were injected, but they did not upregulate hemolymph trehalose. On
      the other hand, injection with Schistocerca gregaria adipokinetic hormone (AKH)
      significantly increased hemolymph trehalose concentration in S. exigua. During
      upregulation of hemolymph trehalose by AKH injection, trehalose degradation
      appeared to be inhibited because expression of trehalase and SeILP1 were
      significantly suppressed while that of trehalose phosphate synthase was not
      significantly changed. Interrogation of a Spodoptera genome database identified
      an S. exigua AKH-like gene and its expression was confirmed. During starvation,
      its expression concentrations were increased, although RNA interference specific
      to the AKH-like hypertrehalosemic factor (SeHTF) gene significantly prevented the
      upregulation of hemolymph trehalose concentrations during starvation. A synthetic
      peptide of SeHTF was prepared and injected into S. exigua larvae. At nanomolar
      concentration, the synthetic SeHTF peptide effectively upregulated hemolymph
      trehalose concentrations. Here we report a novel hypertrehalosemic factor in S.
      exigua (SeHTF).

PMID- 28440595
TI  - Remittances as aid following major sudden-onset natural disasters.
AB  - There is a general assumption, based on macroeconomic studies, that remittances
      will rise following major sudden-onset natural disasters. This is confirmed by a
      few assessments involving country-specific research, and usually short-term data.
      This study, questioning conventional wisdom, reviewed and graphed annual and
      quarterly remittance flows using International Monetary Fund and World Bank data
      from 2000-14 for 12 countries that confronted 18 major natural disasters. It
      found that, regardless of event type, annual remittances rose steadily from 2000
      14 except for after the 2008-09 financial crisis. Post disaster, there was a
      quarterly increase in the majority of cases (confirming previous research) but
      there was seldom an annual increase in the year of the disaster greater than the
      average annual increase in 2000-14. It appears that remittance senders rush to
      provide assistance after a natural disaster, but since their own financial
      situation has not changed, the immediate increase is compensated by a later
      decrease.

PMID- 28440596
TI  - Immunogenicity of a Fully Synthetic MUC1 Glycopeptide Antitumor Vaccine Enhanced
      by Poly(I:C) as a TLR3-Activating Adjuvant.
AB  - Fully synthetic MUC1 glycopeptide antitumor vaccines have a precisely specified
      structure and induce a targeted immune response without suppression of the immune
      response when using an immunogenic carrier protein. However, tumor-associated
      aberrantly glycosylated MUC1 glycopeptides are endogenous structures, "self
      antigens", that exhibit only low immunogenicity. To overcome this obstacle, a
      fully synthetic MUC1 glycopeptide antitumor vaccine was combined with
      poly(inosinic acid:cytidylic acid), poly(I:C), as a structurally defined Toll
      like receptor 3 (TLR3)-activating adjuvant. This vaccine preparation elicited
      extraordinary titers of IgG antibodies which strongly bound human breast cancer
      cells expressing tumor-associated MUC1. Beside the humoral response, the
      poly(I:C) glycopeptide vaccine induced a pro-inflammatory environment, very
      important to overcome the immune-suppressive mechanisms, and elicited a strong
      cellular immune response crucial for tumor elimination.

PMID- 28440597
TI  - External quality assessment for laboratory testing of HLA-B*15:02 allele in
      relation to carbamazepine therapy.
AB  - BACKGROUND: Due to the significant risk of developing Stevens-Johnson syndrome
      (SJS) and toxic epidermal necrolysis (TEN), the use of carbamazepine is not
      recommended in patients carrying the human leukocyte antigen B (HLA-B) *15:02
      allele. In an effort to guarantee reliable community-based HLA-B*15:02 testing
      throughout China, a HLA-B*15:02 genotyping external quality assessment (EQA)
      program was set up. METHODS: In 2016, 10 genomic DNA samples with known HLA
      B*15:02 allele status were sent to 37 laboratories from 16 provinces with a
      request for routine HLA-B*15:02 screening. The samples were validated using
      Sanger sequencing by a reference laboratory. Both genotyping results and clinical
      written reports were evaluated. RESULTS: Thirty-six of the participating
      laboratories correctly identified the HLA-B*15:02 allele status for all EQA
      samples. However, one lab failed to identify any positive challenges. The overall
      analytical sensitivity was 97.3% (180/185 challenges; 95% confidence interval:
      93.8%-99.1%) and the analytic specificity was 100% (185/185; 95% confidence
      interval: 98.0%-100%). A review of the written reports showed that the clinical
      reporting for HLA-B*15:02 detection should be improved. Some essential
      information was missing, most notably laboratory information/contact, therapeutic
      recommendations, and methodology. CONCLUSION: External quality assessment is
      valuable in assessing and improving the quality of laboratory testing of HLA
      B*15:02 allele.

PMID- 28440598
TI  - Corrigendum: Strain-Induced Reactivity in the Dynamic Covalent Chemistry of
      Macrocyclic Imines.

PMID- 28440599
TI  - Corrigendum: Investigation of Binding Behavior between Drug Molecule 5-Fluoracil
      and M4 L4 -Type Tetrahedral Cages: Selectivity, Capture, and Release.

PMID- 28440600
TI  - Impact of atrial fibrillation detected by extended monitoring-A population-based
      cohort study.
AB  - BACKGROUND: The clinical relevance of extended monitoring of AF in the general
      population is unclear. The study evaluated the detection of AF using
      transtelephonic electrocardiography and the clinical relevance of additional AF
      findings, especially with regard to stroke risk and mortality. METHODS: The data
      of 1678 volunteers participating in the tele-ECG-subproject of the Study of
      Health in Pomerania was evaluated. Occurrence of AF as revealed by tele-ECG and
      conventional ECG was evaluated. Associations with mortality, history of stroke,
      and other clinical parameters were analyzed. RESULTS: AF was detected in 21
      subjects (1.3%) by conventional ECG (ECG-AF) and in 43 (2.6%) by tele-ECG. All
      individuals with AF revealed by conventional ECG were also diagnosed to have AF
      by tele-ECG; 22 were diagnosed by tele-ECG only (Tele-AF). During follow-up
      (median: 6.3 years) 42/1635, 1/22, and 5/21 participants died in the no-AF-, tele
      AF-, and ECG-AF groups (p < .001). Whereas, in comparison to the no-AF group, the
      risk of death was higher in the ECG-AF group (HR 9.4; 3.7-23.8; p < .001), there
      was no significant increase in mortality in the tele-AF group (HR 1.9; 0.26-14.0;
      p = .52). Prevalence of stroke history was higher in the ECG-AF group (19%; 5.5
      42%) than with the no-AF (1.9%; 1.3-2.7%; p = .001) and the tele-AF groups (0%; 0
      15%; p = .05). CONCLUSIONS: Tele-ECG identifies significantly more AF cases in a
      population-based setting compared to conventional ECG. The impact of AF diagnosed
      only by extended monitoring differs from conventionally diagnosed AF. Additional
      studies are warranted, since this might have an impact on clinical management.

PMID- 28440601
TI  - Measurement of exhaled breath carbon monoxide in clinical practice: A study of
      levels in Central Pennsylvania community members.
AB  - BACKGROUND AND PURPOSE: Exhaled breath carbon monoxide (eBCO) reading is a useful
      tool for nurse practitioners to evaluate smoking status and other exposures to
      carbon monoxide (CO) to identify risk for cancer and chronic disease. This study
      aimed to measure one community's eBCO and identify potential environmental
      factors that may affect eBCO among nonsmokers. METHODS: Data collected by
      convenience sampling at community health events included self-reported tobacco
      use and potential CO exposure. Means and frequency calculations describe the
      sample, two-sided t-tests determine differences in continuous variables, and chi
      square tests determine differences in frequencies of CO levels between nontobacco
      users exposed to additional CO from their environment and nontobacco users who
      were not. CONCLUSION: As expected, smokers have significantly higher mean eBCO
      than nonsmokers (20.1 ppm vs. 4.4 ppm, p < .001). The self-reported nonsmokers
      (16.2%) had an elevated eBCO (>6 ppm), although there were no environmental
      factors that explained a higher eBCO. IMPLICATIONS FOR PRACTICE: Measuring eBCO
      provides an opportunity for the nurse practitioner to engage in a conversation
      about the impact of smoking and other environmental factors that contribute to
      eBCO and health. Keeping record of patients' smoking status and eBCO in their
      medical record is a valuable measure of the nurse practitioner's delivery of this
      care.

PMID- 28440603
TI  - Can 3D echocardiography replace computed tomographic imaging for aortic annular
      sizing before transcutaneous aortic valve replacement?

PMID- 28440604
TI  - A proposed novel framework for monitoring and evaluation of the cascade of HIV
      associated TB care at the health facility level.
AB  - INTRODUCTION: The rapid and accurate diagnosis of HIV-associated tuberculosis
      (TB), timely initiation of curative or preventative treatment and assurance of
      favourable treatment outcomes is a complex process. The current system of
      monitoring and reporting TB diagnosis and treatment does not include several key
      aspects of the care cascade, and may obscure systematic bottlenecks,
      inefficiencies or sources of sub-optimal care. METHODS: We critically reviewed
      the current World Health Organizations recommended system of monitoring and
      reporting, and identified the following key deficiencies that could limit the
      ability of healthcare workers to identify structural problems in the provision of
      TB/HIV care. RESULTS: We identified the following key deficiencies in the current
      monitoring and evaluation system: (1) an emphasis on national-level reporting and
      programmatic analysis results in a loss of granularity; (2) the absence of a
      general framework to anchor indicators in relation to one another as well as the
      overall goals for TB/HIV collaborative activities; (3) de-linking of TB treatment
      indicators from those for screening and diagnosis; (4) few indicators are tied to
      suggested times for completion of an activity. We defined three distinct stages
      comprising the cascade of HIV-associated TB diagnosis and treatment: (1)
      Screening & Diagnosis, (2) Treatment and (3) Preventive Therapy. We detailed
      major steps within each stage, described potential sources of variability, and
      proposed data elements, process indicators, main outcomes, and retention
      calculations for each stage. CONCLUSION: This proposed framework of monitoring is
      novel in its focus on a cohort experience through the entire scope of the care
      cascade from screening and TB diagnosis through curative or preventive treatment.
      This approach can be applied to all settings at clinic, district or national
      level, and used to identify crucial areas for improvement in order to maximize
      health outcomes for all those affected by the dual epidemics of TB and HIV.

PMID- 28440605
TI  - [Carbapenem resistance in Pseudomonas aeruginosa isolated from urine cultures:
      prevalence and risk factors].
AB  - OBJECTIVE: Pseudomonas aeruginosa is a non-fermentative gram-negative bacillus
      with a great ability to develop resistance to multiple antibiotics, including
      carbapenems, which is a growing problem worldwide. The aim of this study was to
      analyse the prevalence of carbapenem-resistant P. aeruginosa (CRPA) in urine
      cultures and to determine the risk factors associated with the development of
      carbapanem resistance. METHODS: Positive urine cultures to P. aeruginosa between
      September 2012 and September 2014 were identified. We excluded repetitive
      cultures from the same patient. We created a database with different variables,
      including antimicrobial resistance. The prevalence of carbapenem resistance and
      the risk factors for growth of CRPA were analysed. RESULTS: Ninety-one patients
      with positive urine cultures to P. aeruginosa were included. The prevalence of
      CRPA was 22%. The risk factors to CRPA infection in the univariate analysis were:
      congestive heart failure (p=0.02), previous treatment with ampicillin (p=0.04),
      meropenem (p=0.04), piperacillin-tazobactam (p=0.01), trimethoprim
      sulfamethoxazole (p= 0.01) and previous treatment with more than one antibiotic
      (p<0.01). Only congestive heart failure (p<0.01) and previous treatment with more
      than one antibiotic (p<0.01) showed statistically significant differences in the
      multivariate analysis. CONCLUSIONS: The prevalence of CRPA in urine cultures is
      high in our population. We should assess the presence of risk factors as previous
      treatment with more than one antibiotic or comorbidities such as heart failure,
      in order to select an appropriate empirical treatment in patients with severe
      urinary tract infections.

PMID- 28440606
TI  - Pathogenesis and Prevention of Radiation-induced MyocardialFibrosis
AB  - Radiation therapy is one of the most important methods for the treatment of
      malignant tumors. However, inradiotherapy for thoracic tumors such as breast
      cancer, lung cancer, esophageal cancer, and mediastinal lymphoma, theheart,
      located in the mediastinum, is inevitably affected by the irradiation, leading to
      pericardial disease, myocardialfibrosis, coronary artery disease, valvular
      lesions, and cardiac conduction system injury, which are consideredradiation
      induced heart diseases. Delayed cardiac injury especially myocardial fibrosis is
      more prominent, and itsincidence is as high as 20-80%. Myocardial fibrosis is the
      final stage of radiation-induced heart diseases, and it increasesthe stiffness of
      the myocardium and decreases myocardial systolic and diastolic function,
      resulting in myocardialelectrical physiological disorder, arrhythmia, incomplete
      heart function, or even sudden death. This article reviews thepathogenesis and
      prevention of radiation-induced myocardial fibrosis for providing references for
      the prevention andtreatment of radiation-induced myocardial fibrosis.

PMID- 28440607
TI  - Is Height of Prognostic Significance in Breast Cancer Cases?
AB  - Objective: The objective of this study was to investigate the correlation of
      height with prognosis and other prognosticfactors in Turkish breast cancer cases.
      Materials and Methods: We retrospectively reviewed a total of 393 women
      agedbetween 26 and 88 years, diagnosed with stage 1-3 invasive ductal breast
      cancer, treated and followed-up in KayseriEducation and Research Hospital.
      Findings: The mean age at admission was 55.7 years; 77.6% were aged under
      65,56.7% were postmenopausal, 97.4% had undergone modified radical mastectomy,
      47.3% were AJCC stage II, 36.8%N0, 46.0% grade II, 95.4% had received
      chemotherapy, 81.1% radiotherapy and 71.5% hormonotherapy. Height wasunder 151 cm
      in 20.8 %, 151-160 cm in 57.3 % and over 161 in 21.9 %. Follow-up duration
      differed between 0.3and 195.3 months. Mean overal survival (OS) was 125.0 (65.6
      184.3) months and progression free survival was 91.5(37.7-145.2) months, with a
      tendency for better survival in taller individuals but no signficant variation
      betweenheight groups. The 5 and 10-year OS rates were 74.5% and 56.4%, and PFS
      rates were 64.5% and 49.2%. Regardingassociation of height with other prognostic
      factors, a significant correlation was found between height and AJCC stage(p=
      0.011) and estrogen status (ER) (p= 0.043). Conclusion: In conclusion, overal
      survival was found to be longer inpatients with a height between 151 and 160 cm
      than those under 151 cm and over 161 cm. The reason for not obtainingsignificant
      results might be a relatively small number of patients and lack of the evaluation
      of clinical and pathologiccharacteristics together with anthropometric
      measurements in the patient population. Further studies are warranted toclarify
      any association.

PMID- 28440608
TI  - Association of Human Cytomegalovirus with Hodgkin's Disease and Non-Hodgkin's
      lymphomas
AB  - Background and Objective: The human cytomegalovirus (HCMV) can persist lifelong
      as a latent infection andmay result in a series of disorders. Associations with
      both Hodgkin's disease and non-Hodgkin's lymphomas have beenreported. Expression
      of the unique long (UL)138 gene of HCMV is linked with the viral latency phase
      while that of theimmediate-early (IE)1 gene is typical of the viral replication
      phase in patients. This study conducted to determine theprevalence of CMV latent
      infection in histological tissue samples from patients with Hodgkin's and Non
      Hodgkin'slymphomas. Material and Methods: A cross sectional study was carried out
      with a total of 50 paraffin embeddedtissues blocks, including 25 samples for
      Hodgkin's disease and 25 samples for non-Hodgkin's lymphomas. After RNAextraction
      and cDNA preparation, detection of IE1 mRNA was conducted by RT-PCR and
      identification of mRNAUL138 was achieved by nested PCR. Results: Among 25 cases
      of Non-Hodgkin's lymphoma, 5 (20%) were positivefor UL 138 and 1 (4%) for both
      IE1 and UL 138. Among 25 cases of Hodgkin only 1 (4%) was positive for UL 138and
      all were negative for IE1 .Conclusion: A relatively high 20% rate of expression
      of UL 138 was detected in patientswith non-Hodgkin's lymphoma, so that latent CMV
      infection may play a role in development of the disease.

PMID- 28440609
TI  - Clinical Significance of Circulating Serum Cellular Heat Shock Protein 90 (HSP90)
      Level in Patients with Cutaneous Malignant Melanoma
AB  - Background: Cellular heat shock proteins (HSPs) play significant roles in
      sustaining normal cellular conditions.The stimulated expressions of HSPs result
      in cellular stabilization at times of stress, such as cancer. The objective
      ofthis study was to determine the clinical significance of the serum levels of
      HSP90 in melanoma patients. Material andmethods: A total number of 98 melanoma
      patients were enrolled into this study. Serum HSP90 concentrations weredetermined
      by the solid-phase sandwich ELISA method. Age and sex matched 43 healthy controls
      were included inthe analysis. Results: The median age of patients was 51 years,
      ranging from 16 to 85 years. The majority of patientswere male (61%), had lesions
      in axial localizations (54%) and had metastatic disease (61%). Moreover, most of
      thepatients with metastatic disease had M1c diseases (73%). The baseline serum
      HSP90 levels of melanoma patientswere significantly higher than those of the
      control subjects (median values 49.76 v 27.07ng/ml, respectively,
      p<0.001).However, clinical variables, such as age, gender, site of lesion,
      histology, lymph node involvement, stage, serum LDHlevels and response to
      chemotherapy, were found not correlated with serum HSP90 concentrations (p>0.05).
      Moreover,serum HSP90 level was found not prognostic on survival (p=0.683).
      Conclusions: Serum levels of HSP90 may havea diagnostic value in melanoma.
      However, its predictive and prognostic values were not determined.

PMID- 28440610
TI  - Evaluation Expression of Microrna-93 and Integrin Beta8 in Different Types of
      Glioma Tumors
AB  - MicroRNAs (miRNAs), are a type of small non-coding RNAs, that induce mRNA
      degradation or repress translationby binding to the 3'-untranslated region (UTR)
      of its target mRNA. Some specific miRNAs, e.g. miR-93, have beendiscovered to be
      involved in pathological procedures by targeting some oncogenes or tumor
      suppressors in glioma. Inthe present study, real-time RT-PCR data was indicated
      the expression pattern and prognostic value of miR-93 in patientswith types of
      Glioma.MiR-93 expression was significantly decreased in tumor tissue compared
      with normal group braintissues (P<0.001). Low miR-93 expression was significantly
      correlated with progressive tumor grade (P=0.02).Moreover,multivariate analysis
      showed that miR-93 decreased expression (HR, 4.3; 95% CI, 0.8-17.2, P=0.02),
      advanced tumorgrade (HR, 3.1; 95% CI, 0.2-13.9, P=0.04), for integrinbeta8, level
      expression was inverse. Our data was shown that thedown regulation of miR-93 was
      significantly correlated with unfavorable pathological features in patients with
      Glioma.Suggesting that decreased expression of miR-93can be used as a novel
      prognostic factor for this disease.

PMID- 28440611
TI  - The Meningioma 1 (MN1) Gene is an Independent Poor Prognostic Factor in Adult
      Egyptian Acute Myeloid Leukemia Patients
AB  - Aim: To determine the prognostic importance of meningioma 1 (MN1) gene expression
      levels in the context ofother predictive markers for acute myeloid leukemia (AML)
      cases. Methods: MN1 expression was measured in 85newly diagnosed adults younger
      than 60 years by real-time reverse-transcriptase polymerase chain reaction.
      Results: Atdiagnosis 67.4% of cases had elevated MN1 expression, this being
      associated with a worse prognosis, higher incidenceof lymphadenopathy and CD34
      transcript expression (p=0.02 and <0.001, respectively). No other molecular or
      clinicalcharacteristics were significantly associated with MN1expression.
      Patients with high MN1 expression had lowercomplete response rate at day 15
      compared to patients with low MN1 expression (p=0.09) and a significantly
      higherrelapse rate (21.1% versus 7.7%, respectively, p=0.04). Patients with high
      MN1 expression had shorter TTP comparedto those with low expression, p= 0.07.
      Conclusion: MN1 expression may predict outcome in AML patients. The MN1gene and
      micro RNA expression suggest a biological feature that could be used as
      therapeutic targets.

PMID- 28440612
TI  - Association Between XRCC1 and WRN as Genetic Markers of Stability and
      Susceptibility to Cancer in Patients with HIV/AIDS and Cancer: a Cross-Sectional
      Study
AB  - Background: HIV-induced immunodeficiency has been implicated as a key factor for
      risk of cancer. Neoplasia isconsidered to result from accumulation of damage to
      the genome. Polymorphisms in repair genes, such as the XRCC1and WRN, have been
      associated with susceptibility to development of cancer in patients with
      HIV/AIDS. The aimof this study was to analyze the frequency of polymorphisms in
      XRCC1 (Arg399Gln) and WRN (Cys1367Arg) inpatients with HIV/AIDS with or without
      cancer. Materials and Methods: Genotyping for analysis of polymorphismswas
      carried out by PCR (Polymerase Chain Reaction) and RFLP (Restriction Fragment
      Length Polymorphism).Results: In the genotypic and allelic analysis, no increased
      risk of cancer was observed with any genotype or alleleof XRCC1 (Arg399Gln)
      singly (prevalence ratio 2.82; p-value= 0.24). However, with the WRN (Cys1367Arg)
      gene,the heterozygous genotype and arginine allele were associated with increased
      risk (prevalence ratio= 25.62; p-value=0.0001). Correlation analysis showed no
      association between gender and the risk (male p-value= 0.639 and womenp-value>
      1); however, a positive association for the increased risk of cancer was shown
      with XRCC1 (Arg399Arg)wild-type homozygous and WRN (Cys1367Arg) heterozygous (p
      value< 0.001), with heterozygous XRCC1 (Arg399Gln)and WRN (Cys1367Arg) (p-value<
      0.001), and with variant homozygous XRCC1 (Gln399Gln) and heterozygous
      WRN(Cys1367Arg) (p-value< 0.001). Conclusions: There is no increased risk of
      cancer in patients who are HIV/AIDScarriers of the XRCC1 (Arg399Gln) gene singly.
      However, there is a high risk in patients with HIV/AIDS who have theheterozygous
      genotype and the arginine allele in the WRN (Cys1367Arg) gene singly. Those with
      WRN (Cys1367Arg)heterozygote genotype showed a high risk of cancer with all
      genotypes of the XRCC1 (Arg399Gln) gene.

PMID- 28440613
TI  - Constructing a Heterostructural LiNi0.4Mn1.6O4-delta Material from Concentration
      Gradient Framework to Significantly Improve Its Cycling Performance.
AB  - A heterostructural LiNi0.35Mn1.65O4-delta-LiNi0.5Mn1.5O4 was achieved via
      constructing the concentration-gradient material with an average composition of
      LiNi0.4Mn1.6O4-delta. The as-obtained samples were characterized by cross
      sectional scanning electron microscopy and energy dispersive X-ray spectrometry,
      and it was found that the core material LiNi0.35Mn1.65O4-delta is encapsulated
      completely by a concentration-gradient shell with the outmost layer of
      LiNi0.5Mn1.5O4. Demonstrated by high resolution transmission electron microscopy
      and X-ray photoelectron spectroscopy analysis with a low-energy Ar neutral beam
      etching method, the structurally stable P4332 phase on the surface coordinates
      the high conductive Fd3m phase in the bulk without any detectable interface. At
      room temperature, the heterostructural samples deliver the initial discharge
      capacity of 145.1 mAhg-1 at 1 C, close to the theoretical capacity, and the
      capacity retention after 300 cycles was up to 96.5% of the first discharge
      capacity. Moreover, it shows excellent rate capability with discharge capacity of
      144.3 mAhg-1 at 10 C and significantly improved cycling stability with capacity
      retention of 85.51% over 50 cycles between 3.0 and 4.95 V at 55  degrees C. The
      as-obtained material with coordination of two crystallographic structure domains
      is a promising cathode to develop high energy, high power, long lifespan, and low
      cost lithium-ion batteries.

PMID- 28440614
TI  - Chemical Vapor Deposition Growth of Degenerate p-Type Mo-Doped ReS2 Films and
      Their Homojunction.
AB  - Substitutional doping of transition metal dichalcogenide two-dimensional
      materials has proven to be effective in tuning their intrinsic properties, such
      as band gap, transport characteristics, and magnetism. In this study, we realized
      substitutional doping of monolayer rhenium disulfide (ReS2) with Mo via chemical
      vapor deposition. Scanning transmission electron microscopy demonstrated that Mo
      atoms are successfully doped into ReS2 by substitutionally replacing Re atoms in
      the lattice. Electrical measurements revealed the degenerate p-type semiconductor
      behavior of Mo-doped ReS2 field effect transistors, in agreement with density
      functional theory calculations. The p-n diode device based on a doped ReS2 and
      ReS2 homojunction exhibited gate-tunable current rectification behaviors, and the
      maximum rectification ratio could reach up to 150 at Vd = -2/+2 V. The successful
      synthesis of p-type ReS2 in this study could largely promote its application in
      novel electronic and optoelectronic devices.

PMID- 28440615
TI  - Monolith-Supported Amine-Functionalized Mg2(dobpdc) Adsorbents for CO2 Capture.
AB  - The potential of using an amine-functionalized metal organic framework (MOF),
      mmen-M2(dobpdc) (M = Mg and Mn), supported on a structured monolith contactor for
      CO2 capture from simulated flue gas is explored. The stability of the unsupported
      MOF powders under humid conditions is explored using nitrogen physisorption and X
      ray diffraction analysis before and after exposure to humidity. Based on its
      superior stability to humidity, mmen-Mg2(dobpdc) is selected for further growth
      on a honeycomb cordierite monolith that is wash-coated with alpha-alumina. A
      simple approach for the synthesis of an Mg2(dobpdc) MOF film using MgO
      nanoparticles as the metal precursor is used. Rapid drying of MgO on the monolith
      surface followed by a hydrothermal treatment is demonstrated to allow for the
      synthesis of a MOF film with good crystallite density and favorable orientation
      of the MOF crystals. The CO2 adsorption behavior of the monolith-supported mmen
      Mg2(dobpdc) material is assessed using 10% CO2 in helium and 100% CO2,
      demonstrating a CO2 uptake of 2.37 and 2.88 mmol/g, respectively. Excellent
      cyclic adsorption/desorption performance over multiple cycles is also observed.
      This is one of the first examples of the deployment of an advanced MOF adsorbent
      in a scalable, low-pressure drop gas-solid contactor. Such demonstrations are
      critical to the practical application of MOF materials in adsorptive gas
      separations, as structured contactors have many practical advantages over packed
      or fluidized beds.

PMID- 28440616
TI  - Discovery and Characterization of a Eukaryotic Initiation Factor 4A-3-Selective
      Inhibitor That Suppresses Nonsense-Mediated mRNA Decay.
AB  - Eukaryotic initiation factor 4A-3 (eIF4A3) is an Asp-Glu-Ala-Asp (DEAD) box
      family adenosine triphosphate (ATP)-dependent RNA helicase. Subtypes eIF4A1 and
      eIF4A2 are required for translation initiation, but eIF4A3 participates in the
      exon junction complex (EJC) and functions in RNA metabolism including nonsense
      mediated RNA decay (NMD). No small molecules for NMD inhibition via selective
      inhibition of eIF4A3 have been discovered. Here, we identified allosteric eIF4A3
      inhibitors from a high-throughput screening campaign. Chemical optimization of
      the lead compounds based on ATPase activity yielded compound 2, which exhibited
      noncompetitive inhibition with ATP or RNA and high selectivity for eIF4A3 over
      other helicases. The optimized compounds suppressed the helicase activity of
      eIF4A3 in an ATPase-dependent manner. Hydrogen/deuterium exchange mass
      spectrometry demonstrated that the deuterium-incorporation pattern of compound 2
      overlapped with that of an allosteric pan-eIF4A inhibitor, hippuristanol,
      suggesting that compound 2 binds to an allosteric region on eIF4A3. We examined
      NMD activity using a luciferase-based cellular reporter system and a quantitative
      real-time polymerase chain-reaction-based cellular system to monitor levels of
      endogenous NMD substrates. NMD suppression by the compounds correlated positively
      with their ATPase-inhibitory activity. In conclusion, we developed a novel eIF4A3
      inhibitor that targets the EJC. The optimized chemical probes represent useful
      tools for understanding the functions of eIF4A3 in RNA homeostasis.

PMID- 28440617
TI  - Anchoring Tailored Low-Index Faceted BiOBr Nanoplates onto TiO2 Nanorods to
      Enhance the Stability and Visible-Light-Driven Catalytic Activity.
AB  - In this work, a fantastic one-dimensional (1D) BiOBr/TiO2 nanorod (NR)
      heterojunction composite was rationally proposed and designed from the
      perspective of molecular and interface engineering. The fabricated intimately
      connected interfacial heterojunction between two-dimensional BiOBr nanoplates and
      1D TiO2 NRs acts as an interfacial nanochannel to promote efficient interfacial
      charge migration and separation of photogenerated electron-hole pairs. As a
      result, 1D BiOBr/TiO2 NR heterojunctions exhibited outstanding visible-light
      photocatalytic activities and sustained cycling performance. Under visible-light
      irradiation for 120 min, the reduction efficiency of Cr(VI) over the TB-2 sample
      (molar ratio: n(Ti)/n(Bi) = 2:1) is as high as 95.4% without adding any
      scavengers. Furthermore, the sample also shows excellent photodegradation
      activity of RhB with a much higher apparent rate constant of 0.49 min-1 and 88.5%
      total organic carbon removal ratio. Furthermore, the corresponding mechanism of
      enhanced photocatalytic activity is proposed according to comprehensively
      investigated results from photoluminescence spectroscopy, photoelectrochemical
      measurement analysis, and radical trapping experiments. This study provides an
      attractive avenue to design and fabricate highly efficient 1D NR heterojunction
      photocatalysts, which possessed a high application value in the field of
      environmental remediation, especially for wastewater purification.

PMID- 28440618
TI  - Design of Antibacterial Poly(ether sulfone) Membranes via Covalently Attaching
      Hydrogel Thin Layers Loaded with Ag Nanoparticles.
AB  - To inhibit bacteria attachment and the subsequent formation of biofilms on
      poly(ether sulfone) (PES) membranes, poly(sulfobetaine methacrylate)/poly(sodium
      acrylate) antibacterial hydrogel thin layers were covalently attached onto the
      membranes, followed by loading with Ag nanoparticles. In our strategy, double
      bonds were firstly introduced onto the PES membrane surfaces to provide anchoring
      sites, and then the hydrogel layers were synthesized on the membrane surfaces via
      UV light-initiated crosslinking copolymerization. Then, Ag ions were adsorbed
      into the hydrogel layers and reduced to Ag nanoparticles by sodium borohydride.
      The amounts of the adsorbed Ag ions were controlled by the mole ratios of
      carboxylate groups in the hydrogel layers. After attaching the hydrogel layers, a
      typical 3D porous structure was observed by scanning electron microscopy, and the
      surface chemical composition variations were characterized by attenuated total
      reflection-Fourier transform infrared spectroscopy. The live/dead staining,
      inhibition zone, and the optical degree of co-culture solution demonstrated that
      the designed surfaces could not only effectively resist bacteria attachment but
      also kill the surrounding bacteria Escherichia coli and Staphylococcus aureus. It
      was noteworthy that the strong antibacterial ability could be maintained for more
      than 5 weeks. Additionally, the excellent hemocompatibility of the modified
      membranes was confirmed by undetectable plasma protein adsorption, suppressed
      platelet adhesion, prolonged clotting time, low hemolysis ratio, and suppressed
      blood-related complement activation. Cell culture tests indicated that the
      membranes showed no cytotoxicity, but strong anti-cell adhesion properties. The
      proposed method to fabricate antibacterial hydrogel thin layers has great
      potential to be widely used to inhibit the formation of biofilms on various
      biomedical devices.

PMID- 28440619
TI  - Collagen Membranes with Ribonuclease Inhibitors for Long-Term Stability of
      Electrochemical Aptamer-Based Sensors Employing RNA.
AB  - Electrochemical aptamer-based (E-AB) sensors offer advantageous analytical
      detection abilities due to their rapid response time (seconds to minutes),
      specificity to a target, and selectivity to function in complex media.
      Ribonucleic acid (RNA) aptamers employed in this class of sensor offer favorable
      binding characteristics resulting from the ability of RNA to form stable tertiary
      folds aided by long-range intermolecular interactions. As a result, RNA aptamers
      can fold into three-dimensional structures more complex than those of their DNA
      counterparts and consequently exhibit better binding ability to target analytes.
      Unfortunately, RNA aptamers are susceptible to degradation by nucleases, and for
      this reason, RNA-based sensors are scarce or require significant sample
      pretreatment before use in clinically relevant media. Here, we combine the
      usefulness of a collagen I hydrogel membrane with entrapped ribonuclease
      inhibitors (RI) to protect small molecule RNA E-AB sensors from endogenous
      nucleases in complex media. More specifically, the biocompatibility of the
      naturally polymerized hydrogel with encapsulated RI promotes the protection of an
      aminoglycoside-binding RNA E-AB sensor up to 6 h, enabling full sensor function
      in nuclease-rich environments (undiluted serum) without the need for prior sample
      preparation or oligonucleotide modification. The use of collagen as a
      biocompatible membrane represents a general approach to compatibly interface E-AB
      sensors with complex biological samples.

PMID- 28440620
TI  - Water Proton NMR: A Tool for Protein Aggregation Characterization.
AB  - Formulation stability is a critical attribute of any protein-based
      biopharmaceutical drug due to a protein's inherent tendency to aggregate.
      Advanced analytical techniques currently used for characterization of protein
      aggregates are prone to a number of limitations and usually require additional
      manipulations with the sample, such as dilution, separation, labeling, and use of
      special cuvettes. In the present work, we compared conventional techniques for
      the analysis of protein aggregates with a novel approach that employs the water
      proton transverse relaxation rate R2(1H2O). We explored differences in the
      sensitivity of conventional techniques, size-exclusion chromatography (SEC),
      microflow imaging (MFI), and dynamic light scattering (DLS), and water NMR (wNMR)
      toward the presence of monoclonal antibody aggregates generated by different
      stresses. We demonstrate that wNMR outperformed SEC, DLS, and MFI in that it was
      most consistently sensitive to increases in both soluble and insoluble
      aggregates, including subvisible particles. The simplicity of wNMR, its
      sensitivity, and possibility of noninvasive measurements are unique advantages
      that would permit its application for more efficient and higher throughput
      optimization of protein formulations.

PMID- 28440621
TI  - Gas Phase Sensing of Alcohols by Metal Organic Framework-Polymer Composite
      Materials.
AB  - Affinity layers play a crucial role in chemical sensors for the selective and
      sensitive detection of analytes. Here, we report the use of composite affinity
      layers containing Metal Organic Frameworks (MOFs) in a polymeric matrix for
      sensing purposes. Nanoparticles of NH2-MIL-53(Al) were dispersed in a Matrimid
      polymer matrix with different weight ratios (0-100 wt %) and drop-casted on
      planar capacitive transducer devices. These coated devices were electrically
      analyzed using impedance spectroscopy and investigated for their sensing
      properties toward the detection of a series of alcohols and water in the gas
      phase. The measurements indicated a reversible and reproducible response in all
      devices. Sensor devices containing 40 wt % NH2-MIL-53(Al) in Matrimid showed a
      maximum response for methanol and water. The sensor response time slowed down
      with increasing MOF concentration until 40 wt %. The half time of saturation
      response (tau0.5) increased by ~1.75 times for the 40 wt % composition compared
      to devices coated with Matrimid only. This is attributed to polymer
      rigidification near the MOF/polymer interface. Higher MOF loadings (>=50 wt %)
      resulted in brittle coatings with a response similar to the 100 wt % MOF coating.
      Cross-sensitivity studies showed the ability to kinetically distinguish between
      the different alcohols with a faster response for methanol and water compared to
      ethanol and 2-propanol. The observed higher affinity of the pure Matrimid polymer
      toward methanol compared to water allows also for a higher uptake of methanol in
      the composite matrices. Also, as indicated by the sensing studies with a mixture
      of water and methanol, the methanol uptake is independent of the presence of
      water up to 6000 ppm of water. The NH2-MIL-53(Al) MOFs dispersed in the Matrimid
      matrix show a sensitive and reversible capacitive response, even in the presence
      of water. By tuning the precise compositions, the affinity kinetics and overall
      affinity can be tuned, showing the promise of this type of chemical sensors.

PMID- 28440622
TI  - Understanding Carbapenem Translocation through OccD3 (OpdP) of Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa utilizes a plethora of substrate specific channels for the
      uptake of small nutrients. OccD3 (OpdP or PA4501) is an OprD-like arginine uptake
      channel of P. aeruginosa whose role has been implicated in carbapenem uptake. To
      understand the mechanism of selective permeation, we reconstituted single OccD3
      channels in a planar lipid bilayer and characterized the interaction with
      Imipenem and Meropenem, analyzing the ion current fluctuation in the presence of
      substrates. We performed point mutations in the constriction region of OccD3 to
      understand the binding and translocation of antibiotic in OccD3. By mutating two
      key residues in the substrate binding sites of OccD3 (located in the internal
      loop L7 and basic ladder), we emphasize the importance of these residues. We show
      that carbapenem antibiotics follow a similar path as arginine through the
      constriction zone and the basic ladder to translocate across OccD3.

PMID- 28440623
TI  - Biomimetic Superhydrophobic Biobased Polyurethane-Coated Fertilizer with
      Atmosphere "Outerwear".
AB  - The development of efficient biobased controlled-release fertilizers has captured
      much research attention because of the environmental concerns and food scarcity
      problems. In this work, a biomimetic superhydrophobic biobased polyurethane
      coated fertilizer (SBPF) was successfully fabricated by increasing surface
      roughness and reducing surface energy of polyurethane (PU) coating. The green PU
      coating was synthesized from low-cost, biodegradable, and renewable cottonseed
      oil. The nutrient release longevity of SBPF revealed 2-fold enhancement compared
      with the normal biobased PU-coated fertilizer (BPF). The significant improvement
      of nutrient release characteristics can be attributed to the atmosphere
      "outerwear" which ensured the nonwetting contact of water with superhydrophobic
      surfaces in gas state instead of in liquid state. The new concept introduced in
      this study can inform the development of the next generation of biobased
      controlled release fertilizers.

PMID- 28440624
TI  - Acid-Base Catalysis in Glycosidations: A Nature Derived Alternative to the
      Generally Employed Methodology.
AB  - Inverting glycosyltransferases enforce in the active site an intramolecular, acid
      base catalyzed glycosidation that, due to proximity of the donor anomeric carbon
      and the acceptor hydroxyl group, follows an SN2-type reaction. Spacers, tethering
      donor and acceptor via nonreacting functional groups, led in intramolecular
      glycosidations to excellent yields and, independent of the donor anomeric
      configuration, to either the alpha- or the beta-anomer. The requirement of a
      demanding protecting group pattern confines the application of this efficient
      method. Only the method where the 2-hydroxyl group of a mannopyranosyl donor is
      tethered via an acetal spacer to the reacting acceptor functional group is used
      for beta-mannopyranoside synthesis. The most elegant method, tethering donor and
      acceptor covalently to the spacer via the leaving group and the reacting
      functional group, was so far not as efficient as hoped. This method is very
      efficient when donor and acceptor are temporarily assembled through a hydrogen
      bond facilitating a stretched hexagon-like transition state. This follows from
      the stereoselective O-glucopyranosyl trichloroacetimidate transformation into O
      glucopyranosyl phosphate with dibenzyl phosphoric acid as acceptor that can be
      regarded as A?B-C-H acceptor type. Generalizing this concept to the use of
      alcohols as acceptors requires reversible generation of an A-B-C-H adduct where A
      H represents the acceptor (RO-H) and B?C a catalyst that has to fulfill several
      criteria. Among these criteria are low affinity to nitrogen, avoiding glycosyl
      donor activation in the absence of acceptor, and high affinity to oxygen in order
      to generate the A-B-C-H adduct with increased proton acidity. Thus, hydrogen-bond
      mediated self-assembly of donor and acceptor and concomitant donor activation via
      a transition state is available, which enforces an acid-base catalyzed SN2-type
      reaction. It could be shown that PhBF2, Ph2BF, and PhSiF3 are such catalysts that
      fulfill the desired four functions: reversible adduct formation with the
      acceptor, hydrogen-bond mediated tethering of this adduct with the donor, and
      acid- and base-catalysis of the glycosidation. Also Lewis acidic metal salts,
      particularly the dimeric gold(III) chloride, turned out to exhibit excellent B?C
      type catalyst properties. Worth mentioning in this context is the ability of
      gold(III) chloride to regioselectively activate diols. As thioureas have high
      affinity to anions and also to neutral compounds through strong hydrogen bonds,
      their binding to alcohols and concomitant activation of O-glycosyl
      trichloroacetimidates was of interest. Yet, even the acidic N,N'-bis[3,5
      bis(trifluoromethyl)phenyl]-thiourea was unable to catalyze glycosidations.
      However, as a cocatalyst to acids, thiourea exerts a strong effect that, based on
      NMR studies, leads first to a hydrogen-bond mediated catalyst-cocatalyst-acceptor
      complex. This complex activates the donor in an intramolecular, acid-base
      catalyzed reaction that is again closely related to the action of inverting
      glycosyltransferases. Thus, from O-(alpha-glycosyl) trichloroacetimidates, good
      yields of the inversion products, that is, the beta-glycosides, are obtained.
      This novel conceptual approach to glycosidation revealed that for retention of
      configuration in addition a catalytic nucleophile is required that enables
      formation of the alpha-glucoside from the alpha-trichloroacetimidate. Preliminary
      studies with a catalyst possessing this 5-fold function, that is, adduct
      formation with the acceptor, hydrogen-bonding between the reactants, acid and
      base catalysis, and a catalytic nucleophile as part of a chiral framework
      supporting facial selection, exhibited good chances for final success in this
      endeavor.

PMID- 28440625
TI  - Antischistosomal Activity of Pyrido[1,2-a]benzimidazole Derivatives and
      Correlation with Inhibition of beta-Hematin Formation.
AB  - The extensive use of praziquantel against schistosomiasis raises concerns about
      drug resistance. New therapeutic alternatives targeting critical pathways within
      the parasite are therefore urgently needed. Hemozoin formation in Schistosoma
      presents one such target. We assessed the in vitro antischistosomal activity of
      pyrido[1,2-a]benzimidazoles (PBIs) and investigated correlations with their
      ability to inhibit beta-hematin formation. We further evaluated the in vivo
      efficacy of representative compounds in experimental mice and conducted
      pharmacokinetic analysis on the most potent. At 10 MUM, 48/57 compounds resulted
      in >70% mortality of newly transformed schistosomula, whereas 37 of these
      maintained >60% mortality of adult S. mansoni. No correlations were observed
      between beta-hematin inhibitory and antischistosomal activities against both
      larval and adult parasites, suggesting possible presence of other target(s) or a
      mode of inhibition of crystal formation that is not adequately modeled by the
      assay. The most active compound in vivo showed 58.7 and 61.3% total and female
      worm burden reduction, respectively. Pharmacokinetic analysis suggested
      solubility-limited absorption and high hepatic clearance as possible contributors
      to the modest efficacy despite good in vitro activity. The PBIs evaluated in this
      report thus merit further optimization to improve their efficacy and to elucidate
      their possible mode of action.

PMID- 28440626
TI  - Alteration of Diastereoisomeric and Enantiomeric Profiles of
      Hexabromocyclododecanes (HBCDs) in Adult Chicken Tissues, Eggs, and Hatchling
      Chickens.
AB  - The concentrations and enantiomer fractions (EFs) of alpha-, beta-, and gamma
      hexabromocyclododecanes (HBCDs) were measured in chicken diet sources (soil and
      chicken feed), home-raised adult chicken (Gallus domesticus) tissues, eggs during
      incubation, and hatchling chicken tissues. HBCD concentrations were not detected
      0.69 ng/g dry weight (dw) and 25.6-48.4 ng/g dw in chicken feed and soil,
      respectively. HBCDs were detected in all adult chicken tissues, except the brain,
      at median levels of 13.1-44.0 ng/g lipid weight (lw). The proportions of alpha
      HBCD in total HBCDs increased from 51% in soil to more than 87% in adult chicken
      tissues. The accumulation ratios (ARs) of alpha-HBCD from diet to adult chicken
      tissues were 4.27 for liver, 11.2 for fat, and 7.64-12.9 for other tissues,
      respectively. The AR and carry-over rate (COR) of alpha-HBCD from diet to eggs
      were 22.4 and 0.226, respectively. The concentrations of alpha-HBCD in hatchling
      chicken liver (median: 35.4 ng/g lw) were significantly lower than those in
      hatchling chicken pectoral muscle (median: 130 ng/g lw). The EFs of alpha-HBCD
      decreased from soil to adult chicken tissues and from eggs to hatchling chicken
      liver. Meanwhile, the EFs of gamma-HBCD increased from soil to adult chicken
      tissues. These results indicate the preferential enrichment of (-)-alpha-HBCD and
      (+)-gamma-HBCD in chickens. The alteration of diastereoisomeric and enantiomeric
      patterns of HBCDs might be influenced by the different absorption and elimination
      rates of the six HBCD enantiomers as well as variations in HBCD metabolism in
      chickens.

PMID- 28440627
TI  - Composite Microposts with High Dry Adhesion Strength.
AB  - Interfaces with enhanced and tunable adhesion have applications in a broad range
      of fields, including microtransfer printing of semiconductors, grippers on
      robots, and component handling in manufacturing. Here, a composite post structure
      with a stiff core and a compliant shell is used to achieve an enhanced adhesion
      under normal loading. Loading the composite structure in shear significantly
      reduces the effective adhesion strength, thus providing tunability. The composite
      posts can be used as stamps in microtransfer printing processes or as building
      blocks of large-area tunable surfaces composed of arrays of posts. Experimental
      measurements on composite posts with diameters of 200 MUm show a peak adhesion
      strength of 1.5 MPa, a 9 times enhancement in adhesion relative to a homogeneous
      post under normal loading, and also that the adhesion can be reduced by nearly a
      factor of 7 through the application of shear. The adhesion behavior of these
      composite structures was also examined using finite element analysis, which
      provides an understanding of the mechanics of detachment. Finally, the composite
      adhesive posts were used as stamps in a microtransfer printing process in which 5
      MUm thick silicon membranes were retrieved and subsequently printed.

PMID- 28440628
TI  - Edaphic Conditions Regulate Denitrification Directly and Indirectly by Altering
      Denitrifier Abundance in Wetlands along the Han River, China.
AB  - Riparian wetlands play a critical role in retaining nitrogen (N) from upland
      runoff and improving river water quality, mainly through biological processes
      such as soil denitrification. However, the relative contribution of abiotic and
      biotic factors to riparian denitrification capacity remains elusive. Here we
      report the spatiotemporal dynamics of potential and unamended soil
      denitrification rates in 20 wetlands along the Han River, an important water
      source in central China. We also quantified the abundance of soil denitrifying
      microorganisms using nirK and nirS genes. Results showed that soil
      denitrification rates were significantly different between riparian and reservoir
      shoreline wetlands, but not between mountain and lowland wetlands. In addition,
      soil denitrification rates showed strong seasonality, with higher values in
      August (summer) and April (spring) but lower values in January (winter). The
      potential and unamended denitrification rates were positively correlated with
      edaphic conditions (moisture and carbon concentration), denitrifier abundance,
      and plant species richness. Path analysis further revealed that edaphic
      conditions could regulate denitrification rates both directly and indirectly
      through their effects on denitrifier abundance. Our findings highlight that not
      only environmental factors, but also biotic factors including denitrifying
      microorganisms and standing vegetation, play an important role in regulating
      denitrification rate and N removal capacity in riparian wetlands.

PMID- 28440629
TI  - Relevant Features of a Triethylene Glycol Dimethyl Ether-Based Electrolyte for
      Application in Lithium Battery.
AB  - Triethylene glycol dimethyl ether (TREGDME) dissolving lithium
      trifluoromethanesulfonate (LiCF3SO3) is studied as a suitable electrolyte medium
      for lithium battery. Thermal and rheological characteristics, transport
      properties of the dissolved species, and the electrochemical behavior in lithium
      cell represent the most relevant investigated properties of the new electrolyte.
      The self-diffusion coefficients, the lithium transference numbers, the ionic
      conductivity, and the ion association degree of the solution are determined by
      pulse field gradient nuclear magnetic resonance and electrochemical impedance
      spectroscopy. The study sheds light on the determinant role of the lithium
      nitrate (LiNO3) addition for allowing cell operation by improving the
      electrode/electrolyte interfaces and widening the voltage stability window.
      Accordingly, an electrochemical activation procedure of the Li/LiFePO4 cell using
      the upgraded electrolyte leads to the formation of stable interfaces at the
      electrodes surface as clearly evidenced by cyclic voltammetry, impedance
      spectroscopy, and ex situ scanning electron microscopy. Therefore, the lithium
      battery employing the TREGDME-LiCF3SO3-LiNO3 solution shows a stable
      galvanostatic cycling, a high efficiency, and a notable rate capability upon the
      electrochemical conditions adopted herein.

PMID- 28440630
TI  - Hydrolytically Stable Luminescent Cationic Metal Organic Framework for Highly
      Sensitive and Selective Sensing of Chromate Anions in Natural Water Systems.
AB  - Effective detection of chromate anions in aqueous solution is highly desirable
      because of their high solubility, environmental mobility, carcinogenicity, and
      bioaccumulation effect. A new strategy for precise detection of chromate anions
      in the presence of a large excess of other anions, such as Cl-, NO3-, and HCO3-,
      in drinking water and natural water systems remains a challenge. Herein, a
      hydrolytically stable cationic luminescent europium(III)-based metal organic
      framework (MOF), 1, was successfully synthesized and investigated as a
      luminescent sensor that exhibits instant and selective luminescence quenching
      properties toward chromate ions in aqueous solutions. Moreover, 1 can be
      introduced into high-ionic-strength water system (e.g., seawater) for chromate
      detection as a consequence of the excellent sensing selectivity. The real
      environmental application of 1 as a chromate probe is studied in deionized water,
      lake water, and seawater. The detection limits in these aqueous media are
      calculated to be 0.56, 2.88, and 1.75 ppb, respectively. All of these values are
      far below the maximum contamination standard of Cr(VI) in drinking water of 100
      ppb, defined by the U.S. Environmental Protection Agency. This excellent chromate
      sensing capability originates from the fast enrichment of chromate ions in solids
      of 1 from solutions, followed by efficient energy transfer from the MOF skeleton
      to the chromate anion, as demonstrated by solution absorption spectroscopy, X-ray
      diffraction, and chromate uptake kinetics and isotherm investigations. To the
      best of our knowledge, 1 possesses the lowest chromate detection limit among all
      reported MOFs up to date and is the only MOF material reported for chromate
      sensing application under environmentally relevant conditions with high ionic
      strengths.

PMID- 28440632
TI  - Thermally Stable Zinc Disalphen Macrocycles Showing Solid-State and Aggregation
      Induced Enhanced Emission.
AB  - In order to investigate the solid-state light emission of zinc salphen macrocycle
      complexes, 7 dinuclear zinc salphen macrocycle complexes (1-7), with acetate or
      hexanoate coligands, are synthesized. The complexes are stable in air up to 300 
      degrees C, as shown via thermogravimetric analysis (TGA), and exhibit green to
      orange-red emission in solution (lambdaem = 550-600 nm, PLQE <= 1%) and slightly
      enhanced yellow to orange-red emission in the solid state (lambdaem = 570-625 nm,
      PLQE = 1-5%). Complexes 1, 2, 4, 5, and 7 also display aggregation-induced
      enhanced emission (AIEE) when hexane (a nonsolvent) is added to a chloroform
      solution of the complexes, with complex 4 displaying a 75-fold increase in peak
      emission intensity upon aggregation (in 0.25:0.75 chloroform:hexane mixture).

PMID- 28440631
TI  - Elastic and pH-Responsive Hybrid Interfaces Created with Engineered Resilin and
      Nanocellulose.
AB  - We investigated how a genetically engineered resilin fusion protein modifies
      cellulose surfaces. We characterized the pH-responsive behavior of a resilin-like
      polypeptide (RLP) having terminal cellulose binding modules (CBM) and showed its
      binding to cellulose nanofibrils (CNF). Characterization of the resilin fusion
      protein at different pHs revealed substantial conformational changes of the
      protein, which were observed as swelling and contraction of the protein layer
      bound to the nanocellulose surface. In addition, we showed that employment of the
      modified resilin in cellulose hydrogel and nanopaper increased their modulus of
      stiffness through a cross-linking effect.

PMID- 28440633
TI  - Syntheses, Structures, and Characterization of Quaternary Tellurites, Li3MTe4O11
      (M = Al, Ga, and Fe).
AB  - Three new quaternary lithium metal tellurites, Li3MTe4O11 (M = Al, Ga, and Fe),
      have been synthesized through hydrothermal and solid-state reactions by heating a
      mixture of LiOH.H2O, TeO2, and M2O3. The structures of the title compounds have
      been determined by single-crystal and powder X-ray diffraction. Li3MTe4O11 reveal
      three-dimensional (3D) frameworks that consist of MO6 octahedra, TeO3 trigonal
      pyramids, and TeO4 polyhedra. The variable coordination mode of Te4+ within the
      framework leads to the formation of 1D channels that host Li+ cations on both
      tetrahedral and octahedral sites. The bulk and grain boundary Li+ ion
      conductivities for a Li3FeTe4O11 pellet in open air are estimated to be 1.0 * 10
      4 and 2.7 * 10-6 S cm-1, respectively, at room temperature from the impedance
      profile analysis. A lower activation energy of 19.9 kJ mol-1 is obtained for the
      system, which is similar to that of Li10GeP2S12 (24 kJ mol-1). Detailed
      characterizations such as thermal, spectroscopic, and magnetic properties for the
      reported materials are also reported.

PMID- 28440635
TI  - Enantioselective Multicomponent Reaction for Rapid Construction of 1,2,5-Triol
      Derivatives with Vicinal Chiral Centers.
AB  - 1,2,5-Triol derivatives with vicinal chiral centers have been synthesized from
      simple starting materials by one-pot method in good yields and with an excellent
      enantioselectivity. This process was promoted by a chiral secondary amine and
      iridium(I) cocatalyzed three-component reaction of aryldiazoacetates and alcohols
      with enals as electrophiles followed by a reduction with NaBH4. Iridium(I)
      associated oxonium ylide intermediates were efficiently generated and
      successfully trapped by the amine-activated enals via a selective 1,4-addition
      manner, generating enantioselective three-component coupling products.

PMID- 28440634
TI  - m-Carboranylphosphinate as Versatile Building Blocks To Design all Inorganic
      Coordination Polymers.
AB  - The first examples of coordination polymers of manganese(II) and a nickel(II)
      complex with a purely inorganic carboranylphosphinate ligand are reported,
      together with its exhaustive characterization. X-ray analysis revealed 1D
      polymeric chains with carboranylphosphinate ligands bridging two manganese(II)
      centers. The reactivity of polymer 1 with water and Lewis bases has also been
      studied.

PMID- 28440636
TI  - Probing and Comparing the Photobromination and Photoiodination of Dissolved
      Organic Matter by Using Ultra-High-Resolution Mass Spectrometry.
AB  - Photochemical halogenation of dissolved organic matter (DOM) may represent an
      important abiotic process for the formation of natural organobromine compounds
      (OBCs) and natural organoiodine compounds (OICs) within surface waters. Here we
      report the enhanced formation of OBCs and OICs by photohalogenating DOM in
      freshwater and seawater, as well as the noticeable difference in the distribution
      and composition pattern of newly formed OBCs and OICs. By using negative ion
      electrospray ionization coupled with Fourier transform ion cyclotron resonance
      mass spectrometry, various OBCs and OICs were identified during the
      photohalogenation processes in sunlit waters. The respective number of OBCs and
      OICs formed in artificial seawater (ASW) under light radiation was higher than
      that in artificial freshwater (AFW), suggesting a possible role of the mixed
      reactive halogen species. OBCs were formed mainly via substitution reactions and
      addition reactions accompanied by other reactions and distributed into three
      classes: unsaturated hydrocarbons with relatively low oxygen content, unsaturated
      aliphatic compounds, and saturated fatty acids and carbohydrates with relatively
      high hydrogen content. Unlike the OBCs, OICs were located primarily in the region
      of carboxylic-rich alicyclic molecules composed of esterified phenolic,
      carboxylated, and fused alicyclic structures and were generated mainly through
      electrophilic substitution of the aromatic proton. Our findings call for further
      investigation on the exact structure and toxicity of the OBCs and OICs generated
      in the natural environment.

PMID- 28440637
TI  - Identification of Emerging Brominated Chemicals as the Transformation Products of
      Tetrabromobisphenol A (TBBPA) Derivatives in Soil.
AB  - In contrast to the extensive investigation already conducted on
      tetrabromobisphenol A (TBBPA), the metabolism of TBBPA derivatives is still
      largely unknown. In this paper, we characterized unknown brominated compounds
      detected in 84 soil samples collected from sites around three brominated flame
      retardant production plants to determine possible transformation products of
      TBBPA derivatives. In addition to tribromobisphenol A (TriBBPA), dibromobisphenol
      A (DBBPA), and TBBPA, six novel transformation products, TriBBPA mono(allyl
      ether) (TriBBPA-MAE), DBBPA-MAE, hydroxyl TriBBPA-MAE, TBBPA mono(2-bromo-3
      hydroxypropyl ether) (TBBPA-MBHPE), TBBPA mono(2,3-dihydroxypropyl ether) (TBBPA
      MDHPE), and TBBPA mono(3-hydroxypropyl ether) (TBBPA-MHPE) were identified. The
      detection frequencies of these identified chemicals in soil samples ranged from
      17% to 89%, indicating the widespread presence of the transformation products. To
      uncover the possible TBBPA derivative transformation pathways involved, super
      reduced vitamin B12 (cyanocobalamin, (CCAs)) was used to treat TBBPA derivative
      and transformation products in this process were characterized. To our knowledge,
      this is the first study examining the transformation of TBBPA derivatives and the
      first to report several novel associated TBBPA and bisphenol A derivatives as
      transformation products. Our research suggests that ether bond breakage and
      debromination contribute to the transformation of TBBPA derivatives and the
      existence of the novel transformation products. These data provide new insights
      into the fate of TBBPA derivatives in environmental compartments.

PMID- 28440638
TI  - Dielectric Relaxation of the Ionic Liquid 1-Ethyl-3-methylimidazolium Ethyl
      Sulfate: Microwave and Far-IR Properties.
AB  - Dielectric relaxation of the ionic liquid, 1-ethyl-3-methylimidazolium ethyl
      sulfate (EMI+ETS-), is studied using molecular dynamics (MD) simulations. The
      collective dynamics of polarization arising from cations and anions are examined.
      Characteristics of the rovibrational and translational components of polarization
      dynamics are analyzed to understand their respective roles in the microwave and
      terahertz regions of dielectric relaxation. The MD results are compared with the
      experimental low-frequency spectrum of EMI+ETS-, obtained via ultrafast optical
      Kerr effect (OKE) measurements.

PMID- 28440639
TI  - Synthesis of Chromones from 1,1-Diacylcyclopropanes: Toward the Synthesis of
      Bromophycoic Acid E.
AB  - A tandem deprotection-cyclization reaction of 1,1-diacylcyclopropanes is
      described which allows rapid access to structurally diverse 2,3-disubstituted
      chromones in good yields, and with straightforward purification. The utility of
      this reaction is showcased by the construction of the potent antibacterial marine
      natural product bromophycoic acid E scaffold.

PMID- 28440640
TI  - Nucleic Acid Nanocapsules for Enzyme-Triggered Drug Release.
AB  - Herein we describe a nucleic acid functionalized nanocapsule in which nucleic
      acid ligands are assembled and disassembled in the presence of enzymes. The
      particles are fully degradable in response to esterases due to an embedded ester
      cross-linker in the particle's core. During synthesis the nanocapsules can be
      loaded with hydrophobic small molecules and post self-assembly undergo covalent
      cross-linking using copper catalyzed click chemistry. They can then be
      functionalized with thiolated DNA through stepwise thiolyne chemistry using UV
      light irradiation. Additionally, the capsule is compatible with enzyme mediated
      functionalization of a therapeutic mRNA-cleaving DNAzyme at the particle's
      surface. The resulting particle is highly stable, monodisperse in size, and
      maximizes the therapeutic potential of both the particles interior and exterior.

PMID- 28440641
TI  - Thermochemical Investigations of Hydrated Nickel Dication Complexes by Threshold
      Collision-Induced Dissociation and Theory.
AB  - The experimental bond energies of Ni2+(H2O)x complexes, where x = 4-11, are
      determined by threshold collision-induced dissociation using a guided ion beam
      tandem mass spectrometer with an electrospray ionization source. The electrospray
      ionization source produces a distribution of Ni2+(H2O)x complexes, where an in
      source fragmentation technique is employed to access the x = 4-6 complexes and
      control the population of excited isomers. The kinetic energy-dependent cross
      sections are modeled to yield 0 K bond energies for sequential loss of neutral
      water molecules, which are converted to 298 K binding energies. Analysis of the
      primary and secondary water losses from the Ni2+(H2O)x reactant ion complexes, x
      = 4-11, provide accurate thermochemistry for the hydration energies of Ni2+ and
      yield the first experimental values for x = 4 and 5 binding energies. Speculative
      thermochemistry for excited isomers of the x = 4-6 complexes is also obtained.
      Quantum chemical calculations explore the relative energies of possible
      geometries. Theoretical bond energies for ground structures are used for direct
      comparison with experimental values. Our experimental results agree well with
      previously calculated and experimentally obtained binding enthalpies as well as
      with the more extensive quantum chemical calculations performed here.

PMID- 28440642
TI  - Asymmetric Silica Nanoparticles with Tunable Head-Tail Structures Enhance
      Hemocompatibility and Maturation of Immune Cells.
AB  - Asymmetric mesoporous silica nanoparticles (MSNs) with controllable head-tail
      structures have been successfully synthesized. The head particle type is tunable
      (solid or porous), and the tail has dendritic large pores. The tail length and
      tail coverage on head particles are adjustable. Compared to spherical silica
      nanoparticles with a solid structure (Stober spheres) or large-pore symmetrical
      MSNs with fully covered tails, asymmetrical head-tail MSNs (HTMSNs) show superior
      hemocompatibility due to reduced membrane deformation of red blood cells and
      decreased level of reactive oxygen species. Moreover, compared to Stober spheres,
      asymmetrical HTMSNs exhibit a higher level of uptake and in vitro maturation of
      immune cells including dendritic cells and macrophage. This study has provided a
      new family of nanocarriers with potential applications in vaccine development and
      immunotherapy.

PMID- 28440643
TI  - Field Calibration of XAD-Based Passive Air Sampler on the Tibetan Plateau: Wind
      Influence and Configuration Improvement.
AB  - The passive air sampler based on XAD-2 resin (XAD-PAS) has proven useful for
      collecting atmospheric persistent organic pollutants (POPs) in remote regions.
      Whereas laboratory studies have shown that, due to the open bottom of its
      housing, the passive sampling rate (PSR) of the XAD-PAS is susceptible to wind
      and other processes causing air turbulence, the sampler has not been calibrated
      in the field at sites experiencing high winds. In this study, the PSRs of the XAD
      PAS were calibrated at three sites on the Tibetan Plateau, covering a wide range
      in temperature (T), pressure (P) and wind speed (v). At sites with low wind
      speeds (i.e., in a forest and an urban site), the PSRs are proportional to the
      ratio T1.75/ P; at windy sites with an average wind speed above 3 m/s, the
      influence of v on PSRs cannot be ignored. Moreover, the open bottom of the XAD
      PAS housing causes the PSRs to be influenced by wind angle and air turbulence
      caused by sloped terrain. Field calibration, wind speed measurements, and
      computational fluid dynamics (CFD) simulations indicate that a modified design
      incorporating an air spoiler consisting of 4 metal sheets dampens the turbulence
      caused by wind angle and sloped terrain and caps the PSR at ~5 m3/day,
      irrespective of ambient wind. Therefore, the original XAD-PAS with an open bottom
      is suitable for deployment in urban areas and other less windy places, the
      modified design is preferable in mountain regions and other places where air
      circulation is complicated and strong.

PMID- 28440645
TI  - Structural, Electronic, and Magnetic Properties of Iron Disulfide FenS20/+/- (n =
      1-6) Clusters.
AB  - The structural, electronic, and magnetic properties of neutral and charged
      FenS20/+/- (n = 1-6) clusters have been calculated in the framework of the
      density functional theory in the generalized gradient approximation for the
      exchange and correlation. The calculated adiabatic electron affinity and the
      vertical detachment energy are found to be in good agreement with the available
      experimental data. The impact of disulfide-doping of small iron clusters on the
      atomic structure, stability, magnetic moment, and reactivity is determined
      through the analysis of the binding energy per atom, electronic charge transfer,
      spin-polarized electronic densities of states, and global reactivity indicators
      like the electronegativity and chemical hardness. Our results provide an
      exhaustive characterization of these small iron-sulfide particles under vacuum,
      which is the first step to completely understand their role as components of
      proteins.

PMID- 28440644
TI  - Direct Observation of the Ultrafast Evolution of Open-Shell Biradical in
      Photochromic Radical Dimer.
AB  - Delocalized biradicals have been extensively studied because of fundamental
      interests to singlet biradicals and several potential applications such as to two
      photon absorption materials. However, many of the biradical studies only focus on
      the static properties of the rigid molecular structures. It is expected that the
      biradical properties of the delocalized biradicals are sensitive to the subtle
      changes of the molecular structures and their local environments. Therefore, the
      studies of the dynamic properties of the system will give further insight into
      stable radical chemistry. In this study, we directly probe the ultrafast dynamics
      of the delocalized biradical of a photochromic radical dimer,
      pentaarylbiimidazole (PABI), by time-resolved visible and infrared spectroscopies
      and quantum chemical calculations with the extended multistate complete active
      space second-order perturbation theory (XMS-CASPT2). While the photogenerated
      transient species was considered to be a single species of the biradical, the
      present ultrafast spectroscopic study revealed the existence of two transient
      isomers differing in the contributions of biradical character. The origin of the
      two metastable isomers is most probably due to the substantial van der Waals
      interaction between the phenyl rings substituted at the imidazole rings.
      Unraveling the temporal evolution of the biradical contribution will stimulate to
      explore novel delocalized biradicals and to develop biradical-based
      photofunctional materials utilizing the dynamic properties.

PMID- 28440646
TI  - Aqueous Reaction of Dicarbonyls with Ammonia as a Potential Source of Organic
      Nitrogen in Airborne Nanoparticles.
AB  - Nitrogen-containing organic species such as imines and imidazoles can be formed
      by aqueous reactions of carbonyl-containing compounds in the presence of ammonia.
      In the work described here, these reactions are studied in airborne aqueous
      nanodroplets containing ammonium sulfate and glyoxal, methylglyoxal, or
      glycolaldehyde using a combination of online and offline mass spectrometry. N/C
      ratios attributed to the organic fraction of the particles (N/Corg) produced from
      glyoxal and methylglyoxal were quantified across a wide relative humidity (RH)
      range. As the RH was lowered, glyoxal was found to increase N/Corg, attributed to
      "salting-in" with increasing solute concentration, while methylglyoxal led to a
      decrease in N/Corg, attributed to "salting-out". Glycolaldehyde was found to
      evaporate from the droplets rather than react in the aqueous phase and did not
      form particulate-phase organic matter from aerosol drying under any of the
      conditions studied. The results are discussed in the context of ambient
      nanoparticle composition measurements and suggest that aqueous chemistry may
      significantly impact nanoparticle composition and growth during new particle
      formation in locations where emissions of water-soluble dicarbonyls are high,
      such as the eastern United States.

PMID- 28440647
TI  - Controllable Diastereodivergent Synthesis of Pyrrolo[2,1-a]isoquinolines via
      Catalytic Intramolecular Acylsulfenylation of Activated Alkenes.
AB  - A controllable stereoselective synthesis of tetrahydropyrrolo[2,1-a]isoquinoline
      derivatives bearing a sulfur moiety was demonstrated with high
      diastereoselectivity through a catalytic intramolecular acylsulfenylation of
      activated alkenes. This approach involved a catalytic thia-Michael addition
      triggered intramolecular aldol-type tandem sequence. Both cis- and trans-products
      can be readily prepared in moderate to high yields with excellent
      diastereoselectivities in a catalytically atom-economic fashion under the
      optimized mild reaction conditions.

PMID- 28440648
TI  - Fate and Trophic Transfer of Rare Earth Elements in Temperate Lake Food Webs.
AB  - Many mining projects targeting rare earth elements (REE) are in development in
      North America, but the background concentrations and trophic transfer of these
      elements in natural environments have not been well characterized. We sampled
      abiotic and food web components in 14 Canadian temperate lakes unaffected by
      mines to assess the natural ecosystem fate of REE. Individual REE and total REE
      concentrations (sum of individual element concentrations, SigmaREE) were strongly
      related with each other throughout different components of lake food webs.
      Dissolved organic carbon and dissolved oxygen in the water column, as well as
      SigmaREE in sediments, were identified as potential drivers of aqueous SigmaREE.
      Log10 of median bioaccumulation factors ranged from 1.3, 3.7, 4.0, and 4.4 L/kg
      (wet weight) for fish muscle, zooplankton, predatory invertebrates, and
      nonpredatory invertebrates, respectively. [SigmaREE] in fish, benthic
      macroinvertebrates, and zooplankton declined as a function of their trophic
      position, as determined by functional feeding groups and isotopic signatures of
      nitrogen (delta15N), indicating that REE were subject to trophic dilution. Low
      concentrations of REE in freshwater fish muscle compared to their potential
      invertebrate prey suggest that fish fillet consumption is unlikely to be a
      significant source of REE to humans in areas unperturbed by mining activities.
      However, other fish predators (e.g., piscivorous birds and mammals) may
      accumulate REE from whole fish as they are more concentrated than muscle.
      Overall, this study provides key information on the baseline concentrations and
      trophic patterns for REE in freshwater temperate lakes in Quebec, Canada.

PMID- 28440649
TI  - Asymmetric Synthesis of Trisubstituted Tetrahydrothiophenes via in Situ Generated
      Chiral Fluoride-Catalyzed Cascade Sulfa-Michael/Aldol Reaction of 1,4-Dithiane
      2,5-diol and alpha,beta-Unsaturated Ketones.
AB  - A chiral fluoride-catalyzed asymmetric cascade sulfa-Michael/aldol condensation
      reaction of 1,4-dithiane-2,5-diol and a series of alpha,beta-unsaturated ketones
      is described to access chiral trisubstituted tetrahydrothiophene derivatives. The
      target products, including the spiro tetrahydrothiophene derivatives bearing a
      five-, six-, and seven-membered ring, were highly functionalized and showed high
      ee value. This established protocol realized a highly enantioselective reaction
      with a catalytic amount of KF and Song's chiral oligoEG via in situ generated
      chiral fluoride to construct useful heterocyclic skeletons with great complexity.

PMID- 28440651
TI  - Iron-Catalyzed Acyloxyalkylation of Styrenes Using Hypervalent Iodine Reagents.
AB  - Iron-catalyzed acyloxyalkylation of styrene derivatives using hypervalent iodine
      reagents was achieved. The acyloxyalkylation reaction proceeded using various
      types of styrenes and hypervalent iodine reagents. The acyloxyalkylated products
      were obtained in moderate to good yields without loss of the functional groups.
      The reaction proceeded via the formation of radical species derived from
      hypervalent iodine reagents by decarboxylation.

PMID- 28440650
TI  - Comprehensive Computational and Experimental Analysis of Biomaterial toward the
      Behavior of Imidazolium-Based Ionic Liquids: An Interplay between Hydrophilic and
      Hydrophobic Interactions.
AB  - To provide insights into the aggregation behavior, hydration tendency and
      variation in phase transition temperature produced by the addition of ionic
      liquids (ILs) to poly(N-isopropylacrylamide) (PNIPAM) aqueous solution,
      systematic physicochemical studies, and molecular dynamic simulations were
      carried out. The influence of ILs possessing the same [Cl]- anion and a set of
      cations [Cnmim]+ with increasing alkyl chain length such as 1-ethyl-3
      methylimidazolium ([Emim]+), 1-allyl-3-methylimidazolium ([Amim]+), 1-butyl-3
      methylimidazolium ([Bmim]+), 1-hexyl-3-methylimidazolium ([Hmim]+), 1-benzyl-3
      methylimidazolium ([Bzmim]+), and 1-decyl-3-methylimidazolium ([Dmim]+) on the
      phase transition of PNIPAM was monitored by the aid of UV-visible absorption
      spectra, fluorescence intensity spectra, viscosity (eta), dynamic light
      scattering (DLS), and Fourier transform infrared (FTIR) spectroscopy.
      Furthermore, to interpret the direct images and surface morphologies of the
      PNIPAM-IL aggregates, we performed field emission scanning electron microscopy
      (FESEM). The overall specific ranking of ILs in preserving the hydration layer
      around the PNIPAM aqueous solution was [Emim][Cl] > [Amim][Cl] > [Bmim][Cl] >
      [Hmim][Cl] > [Bzmim][Cl] > [Dmim][Cl]. Moreover, to investigate the molecular
      mechanism behind the change in the lower critical solution temperature (LCST) of
      the polymer in the presence of the ILs, a molecular dynamics (MD) study was
      performed. The MD simulation has clearly shown the reduction in hydration shell
      of the polymer after interacting with the ILs at their respective LCST. MD study
      revealed significant changes in polymer conformation because of IL interactions
      and strongly supports the experimental observation of polymer phase transition at
      a temperature lower than typical LCST for all the studied ILs. The driving force
      for concomitant sharp configurational transition has been attributed to the
      displacement of water molecules on the polymer surface by the ILs because of
      their hydrophobic interaction with the polymer.

PMID- 28440652
TI  - An Experimental and Theoretical Study of the Thermal Decomposition of C4H6
      Isomers.
AB  - The chemistry of small unsaturated hydrocarbons, such as 1,3-butadiene (1,3
      C4H6), 1,2-butadiene (1,2-C4H6), 2-butyne (2-C4H6), and 1-butyne (1-C4H6), is of
      central importance to the modeling of combustion systems. These species are
      important intermediates in combustion processes, and yet their high-temperature
      chemistry remains poorly understood, with various dissociation and isomerization
      pathways proposed in the literature. Here we investigate the thermal
      decompositions of 1,3-C4H6, 1,2-C4H6, 2-C4H6, and 1-C4H6 inside a diaphragmless
      shock tube, at postshock total pressures of 26-261 Torr and temperatures ranging
      from 1428 to 2354 K, using laser schlieren densitometry. The experimental work
      was complemented by high-level ab initio calculations, which collectively provide
      strong evidence that formally direct dissociation is the major channel for
      pyrolysis of 1,3-C4H6 and 2-C4H6; these paths have not been previously reported
      but are critical to reconciling the current work and disparate literature
      reports. The reaction mechanism presented here simulates the current experiments
      and experimental data from the literature very well. Pressure- and temperature
      dependent rate coefficients are given for the isomerization, formally direct, and
      direct dissociation paths.

PMID- 28440653
TI  - Hydroxytrifluoromethylation of Alkenes Using Fluoroform-Derived CuCF3.
AB  - Hydroxytrifluoromethylation of alkenes using the fluoroform (CF3H)-derived
      [CuCF3] reagent is described. In the presence of additive B2Pin2 and air, this
      reagent effectively facilitates the addition of hydroxy and trifluoromethyl
      groups across an alkene double bond, a formal hydroxytrifluoromethylation
      process. Various beta-trifluoromethyl alcohols can be synthesized from simple
      alkenes where the ultimate CF3 source is the industrial byproduct fluoroform.

PMID- 28440654
TI  - Holocene Atmospheric Mercury Levels Reconstructed from Peat Bog Mercury Stable
      Isotopes.
AB  - Environmental regulations on mercury (Hg) emissions and associated ecosystem
      restoration are closely linked to what Hg levels we consider natural. It is
      widely accepted that atmospheric Hg deposition has increased by a factor 3 +/- 1
      since preindustrial times. However, no long-term historical records of actual
      atmospheric gaseous elemental Hg (GEM) concentrations exist. In this study we
      report Hg stable isotope signatures in Pyrenean peat records (southwestern
      Europe) that are used as tracers of Hg deposition pathway (Delta200Hg, wet vs dry
      Hg deposition) and atmospheric Hg sources and cycling (delta202Hg, Delta199Hg).
      By anchoring peat-derived GEM dry deposition to modern atmospheric GEM levels we
      are able to reconstruct the first millennial-scale atmospheric GEM concentration
      record. Reconstructed GEM levels from 1970 to 2010 agree with monitoring data,
      and maximum 20th century GEM levels of 3.9 +/- 0.5 ng m-3 were 15 +/- 4 times the
      natural Holocene background of 0.27 +/- 0.11 ng m-3. We suggest that a -0.70/00
      shift in delta202Hg during the medieval and Renaissance periods is caused by
      deforestation and associated biomass burning Hg emissions. Our findings suggest
      therefore that human impacts on the global mercury cycle are subtler and
      substantially larger than currently thought.

PMID- 28440655
TI  - Species- and Tissue-Specific Profiles of Polybrominated Diphenyl Ethers and Their
      Hydroxylated and Methoxylated Derivatives in Cats and Dogs.
AB  - The adverse effects of elevated polybrominated diphenyl ether (PBDE) levels,
      reported in the blood of domestic dogs and cats, are considered to be of great
      concern. However, the tissue distribution of PBDEs and their derivatives in these
      animals is poorly understood. This study determined the concentrations and
      profiles of PBDEs, hydroxylated PBDEs (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs),
      and 2,4,6-tribromophenol (2,4,6-tri-BPh) in the blood, livers, bile, and brains
      of dogs and cats in Japan. Higher tissue concentrations of PBDEs were found in
      cats, with the dominant congener being BDE209. BDE207 was also predominant in cat
      tissues, indicating that BDE207 was formed via BDE209 debromination. BDE47 was
      the dominant congener in dog bile, implying a species-specific excretory capacity
      of the liver. OH-PBDE and MeO-PBDE concentrations were several orders of
      magnitude higher in cat tissues, with the dominant congener being 6OH-BDE47,
      possibly owing to their intake of naturally occurring MeO-PBDEs in food, MeO-PBDE
      demethylation in the liver, and lack of UDP-glucuronosyltransferase, UGT1A6.
      Relatively high concentrations of BDE209, BDE207, 6OH-BDE47, 2'MeO-BDE68, and
      2,4,6-tri-BPh were found in cat brains, suggesting a passage through the blood
      brain barrier. Thus, cats in Japan might be at a high risk from PBDEs and their
      derivatives, particularly BDE209 and 6OH-BDE47.

PMID- 28440656
TI  - Heteroannulation of 3-Nitroindoles and 3-Nitrobenzo[b]thiophenes: A
      Multicomponent Approach toward Pyrrole-Fused Heterocycles.
AB  - A simple, efficient, and general multicomponent reaction involving an enolizable
      ketone, a primary amine, and an N-protected 3-nitroindole was developed for the
      synthesis of a range of functionalized pyrrolo[3,2-b]indoles. The methodology was
      efficaciously utilized for the "pyrroloindoliztion" of natural products, the
      pyrrolization of 3-nitrobenzo[b]thiophene, and the gram-scale synthesis of
      pyrroloindole. Furthermore, a "one-pot" approach for accessing indolo[3,2
      b]indoles was realized.

PMID- 28440657
TI  - Aromaticity of Nonplanar Fully Benzenoid Hydrocarbons.
AB  - The Clar aromatic sextet theory can provide a qualitative description of the
      dominant modes of cyclic pi-electron conjugation in benzenoid molecules and of
      the relative stability among a series of isomeric benzenoid systems. In a series
      of nonplanar fully benzenoid hydrocarbons, the predictions of the Clar theory
      were tested by means of several different theoretical approaches: topological
      resonance energy (TRE), energy effect (ef), harmonic oscillator model of
      aromaticity (HOMA) index, six center delocalization index (SCI), and nucleus
      independent chemical shifts (NICS). To assess deviations from planarity in the
      examined molecules, four different planarity descriptors were employed. It was
      shown how the planarity indices can be used to quantify the effect of
      nonplanarity on the local and global aromaticity of the studied systems.

PMID- 28440658
TI  - Revealing Large-Scale Homogeneity and Trace Impurity Sensitivity of GaAs
      Nanoscale Membranes.
AB  - III-V nanostructures have the potential to revolutionize optoelectronics and
      energy harvesting. For this to become a reality, critical issues such as
      reproducibility and sensitivity to defects should be resolved. By discussing the
      optical properties of molecular beam epitaxy (MBE) grown GaAs nanomembranes we
      highlight several features that bring them closer to large scale applications.
      Uncapped membranes exhibit a very high optical quality, expressed by extremely
      narrow neutral exciton emission, allowing the resolution of the more complex
      excitonic structure for the first time. Capping of the membranes with an AlGaAs
      shell results in a strong increase of emission intensity but also in a shift and
      broadening of the exciton peak. This is attributed to the existence of impurities
      in the shell, beyond MBE-grade quality, showing the high sensitivity of these
      structures to the presence of impurities. Finally, emission properties are
      identical at the submicron and submillimeter scale, demonstrating the potential
      of these structures for large scale applications.

PMID- 28440660
TI  - Implementation of Whole Slide Imaging for Clinical Purposes: Issues to Consider
      From the Perspective of Early Adopters.
AB  - CONTEXT: - There is growing interest in the use of digital pathology, especially
      whole slide imaging, for diagnostic purposes. Many issues need to be considered
      when incorporating this technology into a clinical laboratory. The College of
      American Pathologists (CAP) established a Digital Pathology Committee to support
      the development of CAP programs related to digital pathology. One of its many
      initiatives was a panel discussion entitled "Implementing Whole-Slide Imaging for
      Clinical Use: What to Do and What to Avoid," given for 3 years at the CAP annual
      meetings starting in 2014. OBJECTIVES: - To review major issues to consider when
      implementing whole slide imaging for clinical purposes as covered during the
      panel discussion. DESIGN: - The views expressed and recommendations given are
      based primarily on the personal experience of the authors as early adopters of
      this technology. It is not intended to be an exhaustive review of digital
      pathology. RESULTS: - Implementation is best approached in phases. Early efforts
      are directed toward identifying initial clinical applications and assembling an
      implementation team. Scanner selection should be based on intended use and
      budget. Recognizing pathologist concerns over the use of digital pathology for
      diagnostic purposes, ensuring adequate training, and performing appropriate
      validation studies will enhance adoption. Once implemented, the transition period
      from glass slide to image-based diagnostics will be associated with challenges,
      especially those related to a hybrid glass slide-digital slide workflow.
      CONCLUSIONS: - With appropriate preparation, planning, and stepwise
      implementation, whole slide imaging can be used safely and reliably for frozen
      sections, consultation, quality assurance, and primary diagnosis.

PMID- 28440659
TI  - Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and
      Subtype Selective GABAA Receptor Modulators.
AB  - We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug
      candidates for asthma. Phenolic alpha4beta3gamma2 GABAAR selective compound 1 and
      acidic alpha5beta3gamma2 selective GABAAR positive allosteric modulator compound
      2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness
      (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine
      contracted human tracheal airway smooth muscle strips. Oral treatment of
      compounds 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in
      ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory
      properties. Additionally, compound 1 reduced the number of lung CD4+ T
      lymphocytes and directly modulated their transmembrane currents by acting on
      GABAARs. Excellent pharmacokinetic properties were observed, including long
      plasma half-life (up to 15 h), oral availability, and extremely low brain
      distribution. In conclusion, we report the selective targeting of GABAARs
      expressed outside the brain and demonstrate reduction of AHR and airway
      inflammation with two novel orally available GABAAR ligands.

PMID- 28440661
TI  - Morphological Features and Prognostic Significance of ARID1A-Deficient Esophageal
      Adenocarcinomas.
AB  - CONTEXT: - The clinicopathologic and prognostic significance of ARID1A mutation
      in esophageal adenocarcinoma (EAC) is unknown. OBJECTIVE: - To determine the
      morphological correlates and prognostic significance of ARID1A-deficient EAC.
      DESIGN: - One hundred twenty cases of primary EAC were evaluated for a
      predetermined set of histologic features and immunohistochemistry for ARID1A,
      p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett
      esophagus-associated dysplasia, when feasible. Associations between categorical
      clinicopathologic variables were analyzed by Fisher exact test, and survival
      analysis was performed by a Cox proportional hazards analysis. RESULTS: - The
      study group included 97 men and 23 women (mean age, 66 years). Loss of ARID1A
      expression was seen in 12 of 120 EACs (10%). ARID1A-deficient tumors showed a
      strong correlation with a medullary and mucinous phenotype, and 8 of 12 (67%) had
      at least one feature reminiscent of high microsatellite instability colon
      carcinomas (mucinous or medullary differentiation, marked intratumoral or
      peritumoral lymphoid infiltrate). A mutant p53 pattern was present in 52 of 120
      EACs (43%) and showed no correlation with ARID1A deficiency (P > .05). MLH1 loss
      was present in only 2 of 120 EACs (2%); both of which were also deficient in
      ARID1A. ARID1A-deficient EACs showed a trend toward increased risk of nodal
      metastasis but had no effect on overall patient survival. CONCLUSIONS: - ARID1A
      deficient EACs show a phenotype similar to colon cancer with high microsatellite
      instability but do not appear to have any prognostic significance. Concurrent
      MLH1 loss is not seen in most ARID1A-deficient tumors, suggesting that ARID1A may
      be a primary driver of carcinogenesis in a subset of EACs.

PMID- 28440662
TI  - Step Tracking with Goals Increases Children's Weight Loss in Behavioral
      Intervention.
AB  - BACKGROUND: This study examined the influence of step goals with pedometers to
      improve children's weight loss, physical activity, and psychosocial health during
      obesity treatment. METHODS: Overweight and obese children ages 8-17 years (n =
      105) participated in a 10-week family-based weight management intervention,
      including physical activity, nutrition, and behavioral modification. A quasi
      experimental design was used to group eight cohorts into three conditions: no
      pedometer (n = 24), pedometer only (n = 25), and pedometer with step goals (i.e.,
      500 steps/day weekly increase above baseline; n = 56). Height and weight were
      measured at baseline and week 10 and used to calculate BMI. Analysis of
      covariance was performed to examine difference by condition for change in weight,
      BMI, and BMI z-score, controlling for age and baseline value. Differences in
      steps per day and psychosocial health were compared between the two pedometer
      conditions. RESULTS: Participants were 12.4 +/- 2.5 years of age, including 70%
      girls and 64% African Americans. The pedometer with goals condition significantly
      reduced BMI (p = 0.02) and BMI z-score (p = 0.01) compared with the no-pedometer
      group. The pedometer with goals condition significantly increased steps per day
      (+1185 +/- 425 steps/day) compared with the pedometer-only condition (-162 +/-
      620 steps/day; p < 0.05). Both pedometer groups similarly increased in subjective
      health and quality of life. CONCLUSIONS: Providing children with pedometers and
      individualized step goals was an effective approach to produce weight loss.
      Further work is needed to increase the strength of interventions to achieve
      clinically meaningful weight reduction for children with obesity.

PMID- 28440663
TI  - Acupuncture for Pain and Nausea in the Intensive Care Unit: A Feasibility Study
      in a Public Safety Net Hospital.
AB  - OBJECTIVES: To explore the feasibility and acceptability of providing acupuncture
      treatment to relieve pain and nausea symptoms in intensive care unit (ICU)
      patients. DESIGN: Prospective feasibility study. SETTINGS/LOCATION: Public safety
      net hospital with a 20-bed mixed medical/surgical ICU. SUBJECTS: Patients from
      all services admitted to the ICU from November 14, 2014 to April 2015.
      INTERVENTIONS: Three 20 min acupuncture treatments given for consented patients
      who were experiencing pain and/or nausea, in addition to usual care. OUTCOME
      MEASURES: Primary outcomes assessed were the proportion of patients offered
      acupuncture who accepted it, their perceptions of the effects of acupuncture
      treatment on pain and nausea, and the incidence of adverse effects related to
      acupuncture. Secondary outcomes included medication use, ICU and hospital length
      of stay, and frequency and pattern of Traditional Chinese Medicine (TCM)
      diagnoses. RESULTS: Of the 576 patients admitted to the ICU, 32.2% were deemed
      eligible for acupuncture and 42% of these (8% of total) received it. Self
      reported pain level immediately after treatment decreased from the pain score
      reported immediately before treatment by 2.36 points. The majority of patients
      reported a benefit from acupuncture on symptoms of pain and also an anxiolytic
      effect. No major adverse effects were reported. There was a significant decrease
      in morphine usage after each treatment. The most common single TCM diagnosis was
      Qi and blood stagnation. CONCLUSIONS: Acupuncture is feasible, safe, and
      acceptable in an ICU setting by patients from diverse backgrounds.

PMID- 28440664
TI  - The Effect of Reflexology on the Pain-Insomnia-Fatigue Disturbance Cluster of
      Breast Cancer Patients During Adjuvant Radiation Therapy.
AB  - OBJECTIVE: To evaluate the effects of reflexology treatment on quality of life,
      sleep disturbances, and fatigue in breast cancer patients during radiation
      therapy. METHODS/SUBJECTS: A total of 72 women with breast cancer (stages 1-3)
      scheduled for radiation therapy were recruited. DESIGN: Women were allocated upon
      their preference either to the group receiving reflexology treatments once a week
      concurrently with radiotherapy and continued for 10 weeks or to the control group
      (usual care). OUTCOME MEASURES: The Lee Fatigue Scale, General Sleep Disturbance
      Scale, and Multidimensional Quality of Life Scale Cancer were completed by each
      patient in both arms at the beginning of the radiation treatment, after 5 weeks,
      and after 10 weeks of reflexology treatment. RESULTS: The final analysis included
      58 women. The reflexology treated group demonstrated statistically significant
      lower levels of fatigue after 5 weeks of radiation therapy (p < 0.001), compared
      to the control group. It was also detected that although the quality of life in
      the control group deteriorated after 5 and 10 weeks of radiation therapy (p <
      0.01 and p < 0.05, respectively), it was preserved in the reflexology group,
      which also demonstrated a significant improvement in the quality of sleep after
      10 weeks of radiation treatment (p < 0.05). Similar patterns were obtained in the
      assessment of the pain levels experienced by the patients. CONCLUSIONS: The
      results of the present study indicate that reflexology may have a positive effect
      on fatigue, quality of sleep, pain, and quality of life in breast cancer patients
      during radiation therapy. Reflexology prevented the decline in quality of life
      and significantly ameliorated the fatigue and quality of sleep of these patients.
      An encouraging trend was also noted in amelioration of pain levels.

PMID- 28440665
TI  - Reprogramming of Oncogene Expression in Gingival Mesenchymal Stem Cells Following
      Long-Term Culture In Vitro.
AB  - Mesenchymal stem cells (MSCs) are a promising resource for stem cell therapy for
      the treatment of different neurodegenerative disorders. In particular, dental
      MSCs, given their origin from neural crest and their proneness toward neuronal
      differentiation, may be more suitable for transplantation. However, if MSCs can
      undergo spontaneous transformation and give rise to tumor is still debated. Data
      about transcriptional regulation of oncogenes in MSCs following in vitro
      expansion are not available. In this work, we compared gene expression levels of
      oncogenes in gingival-derived MSCs at passage number 10 and 41. We found that the
      expression of 22 oncogenes was abolished in gingival MSCs at passage number 41
      compared to those at passage number 10, and this may indicate a greater safety of
      high number passage MSCs.

PMID- 28440666
TI  - Relationship between delivery modes and genitourinary syndrome among
      postmenopausal women.
AB  - OBJECTIVES: Many postmenopausal women suffer from genitourinary syndrome of
      menopause (GSM) due to the lack of estrogen. This study aimed to evaluate the
      relationship between mode of delivery and GSM among postmenopausal women.
      METHODS: We performed a case-control study of women who had had either vaginal
      delivery or Cesarean section. Data were collected through a sociodemographic
      questionnaire and a check list for assessing signs and symptoms of GSM.
      Subjective symptoms of vaginal atrophy (dryness, dyspareunia, itching, burning
      and paleness), pH of the vagina and maturation index were assessed and recorded.
      Data were analyzed using the chi2 test and independent t-test. RESULTS: A total
      of 125 postmenopausal women were recruited (65 with a history of normal vaginal
      delivery (NVD) and 60 with a history of Cesarean section). Vaginal pH was more
      commonly lower (pH 5-5.49) in the NVD group (50.8% vs. 40%) (p < 0.001). The
      maturation index was also better in the NVD group (42.7 +/- 6.34 vs. 24.08 +/-
      8.2) (p < 0.001). All symptoms of vaginal atrophy including paleness, dryness,
      itching, dyspareunia and burning were significantly less in the NVD group
      compared to the Cesarean section group (p < 0.05). CONCLUSION: Postmenopausal
      women with a history of normal vaginal delivery were less likely to have GSM
      compared to the women with a history of Cesarean section. Other prospective
      studies can explore this relationship better.

PMID- 28440667
TI  - Camelus dromedarius glucose transporter 4: in silico analysis, cloning,
      expression, purification and characterisation in E. coli.
AB  - Camels have exceptional carbohydrate metabolism as their plasma glucose level is
      high and have low whole body insulin sensitivity, similar to that observed in
      type 2 diabetes patients. We aimed at studing an important component of insulin
      signalling pathway, the GLUT4, in camel. Camelus dromedarius GLUT4 (CdGLUT4) CDS
      is 1530 nucleotide in length that encodes for a 55KDa protein. CdGLUT4 has 23
      amino acid substitutions and 3N-glycosylation sites, compared to 2 in Human
      GLUT4. 3 D structures of CdGLUT4 and HsGLUT4 generated by homology modelling
      revealed conservation of characteristic signature motifs. CdGLUT4 was cloned and
      expressed optimally in C43(DE3)pLysS strain and maximum detergent solubility was
      observed in n-Dodecyl-beta-d-maltopyranoside. These preliminary data provide
      information on residual differences between CdGLUT4 and HsGLUT4 that may be
      responsible for camel's unique glucose metabolism. These differences are
      postulated to assist in designing and development of efficacious GLUT4 that might
      help in management of diabetic patients.

PMID- 28440668
TI  - Tweeting influenza vaccine to cardiovascular health community.
AB  - Globally, among infectious diseases, influenza is one of the leading causes of
      morbidity and mortality. Individuals with chronic conditions, including
      cardiovascular disease and diabetes, are particularly vulnerable to complications
      of an influenza infection. The European Society of Cardiology recommended annual
      influenza vaccinations for patients with cardiovascular disease. Numerous studies
      have suggested a link between influenza and increased risk of cardiovascular
      events. Despite its proven benefits, little is known about the reason for the
      underutilization of influenza vaccination. We present the findings of an
      assessment of patients' perception of the influenza vaccine and the reason for
      its underutilization, by data mining from Twitter.

PMID- 28440669
TI  - Can multiphase dynamic CT angiography provide a better assessment of aortic
      dissection compared with the standard triphasic protocol?
AB  - Background Acute aortic dissection (AD) is a life-threatening medical emergency.
      It has been debated whether the multiphase dynamic computed tomography
      angiography (CTA) protocol is superior to the standard triphasic protocol for
      revealing the characteristics of AD. Purpose To examine two multiphase dynamic
      protocols, Dynamic four-dimensional (4D) CTA using the shuttle mode and Flash 4D
      CTA using the high-pitch mode for the assessment of AD and to compare them with
      the standard triphasic protocol. Material and Methods A total of 54 consecutive
      patients were randomly and equally assigned to three groups and scanned with a
      second-generation DSCT scanner. Groups A, B, and C were assessed with the Dynamic
      4D CTA in the shuttle mode, the Flash 4D CTA in the high-pitch mode, and the
      standard triphasic acquisition protocol, respectively. Image quality of all
      patients was evaluated. The effective radiation dose (ED) was recorded. Results
      In 54 patients, CTA images could display the true and false lumens, the intimal
      flap, the entry tear, and branch vessel involvement in the AD. Compared with
      group C, additional diagnostic information was obtained in groups A and B,
      including the dynamic enhancement delay between the true and false lumens (A =
      18, B = 18); the presence of membrane oscillation (A = 8, B = 14); dynamic
      ejection of the contrast material from the true lumen into the false lumen (A =
      6, B = 7); and the dynamic obstruction of the left renal artery (B = 2). The ED
      in these three groups was significantly different ( P < 0.05). Conclusion
      Compared to the standard triphasic protocol, the multiphase dynamic CTA protocol
      is feasible and is able to reveal additional diagnostic information. Therefore,
      we recommend using the high-pitch, dual-source multiphase dynamic CTA to assess
      ADs.

PMID- 28440670
TI  - Cardiac magnetic resonance based evaluation of aortic stiffness and epicardial
      fat volume in patients with hypertension, diabetes mellitus, and myocardial
      infarction.
AB  - Background Aortic stiffness and epicardial fat relate to cardiovascular risk.
      Their relationship with each other and their role with hypertension, diabetes
      mellitus (DM), and myocardial infarction (MI) can be evaluated by cardiac
      magnetic resonance (CMR). Purpose To explore an association between aortic
      stiffness and epicardial as well as paracardial fat volume (EFV and ParaFV,
      respectively) in hypertensive patients and to relate the results to the presence
      of DM and MI. Material and Methods A total of 156 hypertensive and 20 non
      hypertensive participants were examined at 1.5 Tesla. A 2D-velocity-encoded
      sequence was acquired to assess aortic pulse wave velocity (PWV in m/s) as a
      measure of aortic stiffness. A 3D-Dixon sequence was used to determine EFV and
      ParaFV. Results PWV correlated with EFV (R = 0.474; P < 0.001), but not with
      ParaFV. Fat volumes (in mL/m2) and PWV were lower in non-hypertensive controls
      compared to hypertensive patients. EFV and PWV were significantly higher in
      diabetic hypertensive patients without MI (n = 19; PWV: 10.4 +/- 2.9; EFV: 92.5
      +/- 19.3) compared to hypertension-only patients (n = 84 [no DM or MI]; EFV: 64.8
      +/- 25.1, PWV: 9.0 +/- 2.6; P < 0.05). Logistic regression analysis showed a
      significant association between the presence of a MI and a higher EFV ( P <
      0.05), but not with PWV ( P = 0.060) or ParaFV ( P = 0.375). Conclusion A
      relationship between aortic stiffness and EFV was found in hypertensive patients.
      Both were increased in the presence of DM; however, only EFV was increased in the
      presence of MI. This may relate to the PWV lowering effect of the
      antihypertensive medication used by hypertensive patients and underscores the
      benefit of EFV assessment in this regard.

PMID- 28440671
TI  - Domperidone: The Forbidden Fruit.

PMID- 28440672
TI  - Definitions and participant characteristics of frequent recurrent headache types
      in clinical trials: A systematic review.
AB  - Background Clear definitions of study populations in clinical trials may
      facilitate application of evidence to clinical populations. This review aimed to
      explore definitions of study populations in clinical trials on migraine, tension
      type headache, cluster headache, and cervicogenic headache. Methods We performed
      a systematic review of clinical trials investigating treatment efficacy for
      migraine, tension-type headache, cluster headache, and cervicogenic headache. We
      extracted data on diagnosis, inclusion criteria and baseline headache
      characteristics. Results Of the 229 studies reviewed, 205 studies (89.5%) defined
      their populations in adherence to the International Classification of Headache
      Disorders (ICHD) criteria. Some studies ( n = 127, 55.5%) specified diagnosing
      through interview, clinical examination and diary entry. The most commonly
      reported inclusion criteria were pain intensity for migraine and tension-type
      headache studies ( n = 123, 66.1% and n = 21, 67.7%, respectively), episode
      frequency ( n = 5, 71.4%) for cluster headache studies, and neck-related pain for
      cervicogenic headache studies ( n = 3, 60%). Few studies reported details on the
      extent to which diagnostic criteria were present at baseline. Conclusions ICHD is
      routinely used in defining populations in headache studies. Details of baseline
      headache characteristics were not as consistently reported.

PMID- 28440673
TI  - Mechanisms of craniofacial pain.
AB  - Aim To provide an overview of mechanisms underlying craniofacial pain; to
      highlight peripheral and central adaptations that may promote chronification of
      pain in craniofacial pain states such as migraine and temporomandibular disorders
      (TMD). Background Pain is a common symptom associated with disorders involving
      craniofacial tissues including the teeth and their supporting structures, the
      temporomandibular joint and the muscles of the head. Most acute painful
      craniofacial conditions are easily recognized and well managed, but others,
      especially those that are chronic (e.g., migraine, TMD and trigeminal
      neuropathies), present clinical challenges. Preclinical studies have provided
      substantial information about the anatomical and physiological mechanisms related
      to the initiation and modulation of nociceptive signals in the trigeminal system.
      While knowledge of the mechanisms underlying chronic craniofacial pain remains
      limited, both clinical and preclinical investigations suggest that changes in
      afferent inputs to the brain as well as in brain structure and modulatory
      pathways occur in chronic pain. Collectively, these changes result in
      amplification of nociception that promotes and sustains craniofacial chronic pain
      states. Conclusions The increased understanding gained of the physiological and
      pathological processing of nociception in the trigeminal system has provided new
      perspectives for the mechanistic understanding of acute craniofacial pain
      conditions and the peripheral and central adaptations that are related to pain
      chronification. Such knowledge may contribute to improvements in currently
      available treatments as well as to the development of novel analgesic therapies.

PMID- 28440674
TI  - Late talkers and later language outcomes: Predicting the different language
      trajectories.
AB  - PURPOSE: The aim of the current study was to investigate the risk factors present
      at 2 years for children who showed language difficulties that persisted from 2 to
      10 years and difficulties that emerged later, at 10 years. METHOD: Participants
      (n = 783) were drawn from the Raine Study in Western Australia. Patterns of
      change from 2 to 10 years were identified based on child performance on the
      Language Development Survey and the Clinical Evaluation of Language Fundamentals,
      respectively. Logistic regression analyses were conducted to test whether
      parental, family and child characteristics present at 2 years predicted poorer
      language outcomes at age 10. RESULT: Across the 8 year period, 5.6% of the
      children displayed consistently low language skills, 5.9% improved skills and
      23.2% deteriorated skills. Compared to children with consistently typical skills,
      the deteriorated group was more likely to have mothers who smoked during
      pregnancy, fathers with incomplete secondary education, low family income, poor
      early literacy environment and be male. Children showing consistently low
      language skills were more likely to have mothers who smoked during pregnancy than
      late talkers whose early delays improved. CONCLUSION: Results provide evidence of
      some modifiable risk factors at 2 years which are associated with language
      outcome.

PMID- 28440675
TI  - Near-infrared spectroscopy (NIRS) to detect traumatic intracranial haematoma: A
      systematic review and meta-analysis.
AB  - OBJECTIVES AND METHODS: Head injury is the most common trauma presentation to UK
      emergency departments, with around 1.2 million patients each year. The key
      management principal for this time critical illness remains early surgical
      intervention. With the development of handheld near-infrared spectroscopy (NIRS)
      devices, there is now the possibility of triaging and diagnosing these patients
      immediately, where computed tomography (CT) scanner is unavailable. NIRS has two
      related but distinct potential uses within clinical medicine. Firstly, as a
      triage tool both in hospital and prehospital settings by doctors, nurses or
      paramedics as determined by its negative predictive value (NPV). Secondly, as a
      diagnostic aid as determined by its positive predictive value (PPV). The aim of
      this systematic review and meta-analysis is therefore to interrogate the current
      literature on NIRS in detecting intracranial haematomas. RESULTS: NIRS technology
      has a cross-study sensitivity of 78%, specificity of 90%, PPV of 77%, and a NPV
      of 90%, which does not meet current standards as a diagnostic/triage tool in the
      populations studied. Additionally, its use is limited to those without
      extracranial injuries and may also be complicated by long scan times. CONCLUSION:
      Larger and more heterogeneous studies are required for specifically evaluating
      NIRS performance in detecting intracranial lesions requiring emergency
      evacuation.

PMID- 28440676
TI  - Attitudes of Chinese Adults to Breastfeeding in Public: A Web-Based Survey.
AB  - OBJECTIVE: To explore Chinese adults' perceptions and attitudes toward
      breastfeeding in public places. MATERIALS AND METHODS: This was a web-based
      survey including 10 items on breastfeeding participants (N = 2,021) who were
      recruited by convenience sampling. RESULTS: Almost 95% believed that public
      places should have lactation rooms, 86% thought it was acceptable for mothers to
      breastfeed in this location, and 65% of respondents agreed that it was acceptable
      for mothers to breastfeed in public. Though 47% believed that viewing women
      breastfeeding in public was embarrassing, more than 80% felt that breastfeeding
      in public was appropriate and decent and did not violate social morality. More
      than 90% of respondents approved of policies supporting breastfeeding in public.
      Women, married people, those who had children, had some knowledge about
      breastfeeding, or had the experience of viewing women breastfeeding in public
      were more likely to hold positive perceptions and attitudes toward breastfeeding
      in public places. CONCLUSIONS: Prior experience and knowledge about breastfeeding
      have a great influence on people's perceptions and attitudes toward breastfeeding
      in public, so education about breastfeeding is very important. Breastfeeding
      education should not only include the techniques of breastfeeding practices but
      also include information policies that support breastfeeding in public, including
      the importance of lactation rooms.

PMID- 28440677
TI  - No association between estrogen receptor gene polymorphisms and premature
      thelarche in girls.
AB  - OBJECTIVE: Premature thelarche (PT) is a benign, nonprogressive condition defined
      as isolated breast development. While the pathophysiology of PT remains unclear,
      increased sensitivity to estrogen may cause PT. The aim of this study was to
      investigate the association between polymorphisms in the estrogen receptor alpha
      (ERalpha) gene and PT in girls. METHODS: In this case-control study, we examined
      96 girls referred for early breast development (before the age of 8 years). The
      control group included healthy Korean females with normal pubertal progression.
      Anthropometric and hormonal parameters were measured and PvuII and XbaI ERalpha
      gene polymorphisms were evaluated by PCR. Out of the 96 girls, all coding exon
      and exon-intron boundaries of ERalpha were sequenced from the DNA of 46 girls.
      RESULTS: There was no significant difference in the distribution of PvuII and
      XbaI polymorphisms between patients and controls. However, the carriers of XbaI
      polymorphisms had more advanced Tanner stage than did the non-carriers. Also,
      four ERalpha gene polymorphisms were previously identified, but these
      polymorphisms had no clinical significance. CONCLUSION: No association was found
      between the ERalpha gene polymorphisms and PT in girls. However, XbaI
      polymorphisms may contribute to early breast budding.

PMID- 28440678
TI  - Involvement of Primary Care Physicians in the Decision Making and Care of
      Patients With Breast Cancer.
AB  - Purpose Collaborative care between cancer specialists and primary care providers
      (PCPs) may improve the delivery of high-quality cancer care. Yet, patient
      perspectives about how involved the PCPs were in their breast cancer care and
      treatment decisions remain unknown. Patients and Methods A weighted random sample
      of women newly diagnosed with breast cancer in 2013 to 2014, as reported to the
      SEER registries in Los Angeles, California, and Georgia, were sent a survey
      approximately 6 months after diagnosis (N = 2,279, 71% response rate). The
      distributions of patient-perceived PCP quality (six questions about PCP access
      and awareness of values) and the following three measures of patient-reported PCP
      involvement were assessed: how informed the respondent felt her PCP was about her
      breast cancer (engagement); how often the respondent talked with her PCP
      (communication); and how often the respondent felt the PCP participated in
      treatment decisions (participation). Adjusted mean scores of patient-reported
      satisfaction with and deliberation about the surgical treatment decision were
      then compared across levels of PCP engagement, communication, and participation
      using multivariable linear regression. Results The majority of women in this
      sample perceived high PCP quality (63.6%), high PCP breast cancer engagement
      (66.2%), and high PCP communication (69.1%). More than a third of women (35.4%)
      reported that their PCP participated in their treatment decisions. Higher PCP
      engagement was associated with higher decision satisfaction when compared with
      low PCP engagement (adjusted P = .003). Conclusion Patient perceptions of PCP
      quality and PCP involvement in breast cancer care during treatment are high for
      most women, and PCPs often participate in breast cancer treatment decisions.
      However, PCP involvement did not lead to meaningful improvements in patients'
      appraisals of their decision making.

PMID- 28440679
TI  - Cervical cancer in sub-Saharan Africa: a preventable noncommunicable disease.
AB  - INTRODUCTION: Infections caused by high-risk human papillomavirus (HPV) are
      responsible for 7.7% of cancers in developing countries, mainly cervical cancer.
      This disease is steadily increasing in sub-Saharan Africa, with more than 75,000
      new cases and 50,000 deaths yearly, further increased by HIV infection. Areas
      covered: The current status of cervical cancer associated with HPV in sub-Saharan
      Africa has been systematically revised. The main issues discussed here are
      related to the public health burden of cervical cancer in sub-Saharan Africa and
      predictions for the coming decades, including molecular epidemiology and
      determinants of HPV infection in Africa, and promising prevention measures
      currently being evaluated in Africa. Expert commentary: By the year 2030,
      cervical cancer will kill more than 443,000 women yearly worldwide, most of them
      in sub-Saharan Africa. The increase in the incidence of cervical cancer in Africa
      could counteract the progress made by African women in reducing maternal
      mortality and longevity. Nevertheless, cervical cancer is a potentially
      preventable noncommunicable disease, and intervention strategies to eliminate
      cervical cancer as a public health concern should be urgently implemented.

PMID- 28440680
TI  - Efficacy and safety of baricitinib in Japanese patients with active rheumatoid
      arthritis: A 52-week, randomized, single-blind, extension study.
AB  - OBJECTIVES: The objective of this study is to evaluate the efficacy and safety of
      long-term (64 weeks; 52-week extension of a 12-week study) baricitinib treatment
      in Japanese patients with active rheumatoid arthritis (RA) despite methotrexate
      therapy. METHODS: Patients (N = 145) with active RA were randomized to placebo,
      1mg, 2mg, 4mg, or 8mg baricitinib for the first 12 weeks. During the 52-week
      extension period, patients on 4mg or 8mg baricitinib remained on the same dose
      and all other patients were re-randomized to 4mg or 8mg baricitinib. Most
      patients on 8mg baricitinib were switched to 4mg by week 64 (protocol amendment);
      data analysis was based on the treatment group at the beginning of the extension
      period. RESULTS: Increases in the American College of Rheumatology (ACR) response
      rates (ACR20, ACR50, and ACR70) observed during the first 12 weeks were
      maintained during the extension period, accompanied by improvements in ACR core
      components. At week 64, a large proportion of patients (>40%) had low disease
      activity. Most treatment-related adverse events were mild or moderate; herpes
      zoster was the most common reason (11/27 patients) for discontinuation.
      CONCLUSIONS: The efficacy and safety profile of baricitinib was maintained during
      long-term treatment of Japanese patients with RA and background methotrexate
      therapy. Clinicaltrials.gov NCT01469013; Funding: Eli Lilly and Incyte.

PMID- 28440681
TI  - Discovery and preclinical development of dasabuvir for the treatment of hepatitis
      C infection.
AB  - INTRODUCTION: Hepatitis C virus (HCV) is a leading cause of liver-related
      morbidity and mortality. Positively, the introduction of new directly-acting
      antivirals (DAAs) have led to dramatic improvements in response rates to
      antiviral therapy. Furthermore, newer generations of DAAs have demonstrated
      better safety profiles as well as efficacy than older generations. Current
      treatment recommendations are based on different combinations of DAAs. Current
      combination therapies rely on agents that target the different steps of viral
      replication by using different molecules from various DAAs families. Areas
      covered: In this review, the authors summarize data from of one of the recently
      developed NS5B polymerase inhibitors, dasabuvir, formerly known as ABT-333.
      Herein, the authors discuss the drug discovery data for dasabuvir including data
      from preclinical, toxicological resistance studies. The authors also review
      dasabuvir's clinical efficacy across various clinical challenges, in addition to
      its limitations in clinical practice. Expert opinion: Dasabuvir represents an
      important medical advance when used as a combination therapy for HCV.
      Unfortunately, it does present limitations like low genotypic coverage and
      further research is still required to address some of the lingering issues.

PMID- 28440685
TI  - Work environment: An opportunity for ground-breaking collaborations in
      cardiovascular disease prevention.

PMID- 28440686
TI  - Severe ovarian hyperstimulation syndrome after combined GnRH-agonist and low-dose
      human chorionic gonadotropin trigger in a patient with a single kidney.
AB  - Ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone
      agonist (GnRH-a) trigger is rare. Here, we report a case of severe OHSS after
      combined GnRH-a and low-dose human chorionic gonadotropin (hCG) trigger in a
      patient with a single kidney. The patient is a 32-year-old women with a two-year
      history of infertility. The patient's history was significant for a single
      kidney, that is, she had donated a kidney to a family member three years ago. The
      patient underwent controlled ovarian stimulation (COS) for in vitro fertilization
      (IVF) and received a combined 2 mg GnRH-a and 1500 IU hCG ovulatory trigger.
      Estradiol (E2) levels on the day of and after the trigger were 3800 pg/mL and
      4001 pg/mL, respectively. Four days after the trigger, the patient began
      experiencing nausea, abdominal distention and dyspnea, and her blood testing
      revealed hemoconcentration (hemoglobin: 16.9 g/dL; hematocrit: 51.0%) and an
      elevated creatinine level (1.16 mg/dL). Fresh embryo transfer was deferred. The
      patient was admitted to the hospital for fluid monitoring and prophylactic
      anticoagulation. Following inpatient management, her hemoglobin, hematocrit and
      creatinine levels normalized. The current report highlights that the systemic
      effects of OHSS can be accentuated in patients with preexisting renal disease or
      a single kidney.

PMID- 28440687
TI  - The consequence of spatial visual processing dysfunction caused by traumatic
      brain injury (TBI).
AB  - OBJECTIVE: A bi-modal visual processing model is supported by research to affect
      dysfunction following a traumatic brain injury (TBI). TBI causes dysfunction of
      visual processing affecting binocularity, spatial orientation, posture and
      balance. Research demonstrates that prescription of prisms influence the
      plasticity between spatial visual processing and motor-sensory systems improving
      visual processing and reducing symptoms following a TBI. RATIONALE: The rationale
      demonstrates that visual processing underlies the functional aspects of
      binocularity, balance and posture. The bi-modal visual process maintains
      plasticity for efficiency. Compromise causes Post Trauma Vision Syndrome (PTVS)
      and Visual Midline Shift Syndrome (VMSS). Rehabilitation through use of lenses,
      prisms and sectoral occlusion has inter-professional implications in
      rehabilitation affecting the plasticity of the bi-modal visual process, thereby
      improving binocularity, spatial orientation, posture and balance Main outcomes:
      This review provides an opportunity to create a new perspective of the
      consequences of TBI on visual processing and the symptoms that are often caused
      by trauma. It also serves to provide a perspective of visual processing
      dysfunction that has potential for developing new approaches of rehabilitation.
      CONCLUSIONS: Understanding vision as a bi-modal process facilitates a new
      perspective of visual processing and the potentials for rehabilitation following
      a concussion, brain injury or other neurological events.

PMID- 28440688
TI  - Simultaneous Identification of Campylobacter jejuni, Campylobacter coli, and
      Campylobacter lari with SmartCycler-Based Multiplex Quantitative Polymerase Chain
      Reaction.
AB  - BACKGROUND: Consumption of Campylobacter contaminated food or water is a leading
      cause of human acute gastroenteritis. Campylobacter jejuni, Campylobacter coli,
      and Campylobacter lari account for over 95% of total Campylobacter infections. A
      multiplex quantitative polymerase chain reaction (qPCR) for simultaneous
      identification of C. jejuni, C. coli, and C. lari was developed for use with the
      SmartCycler II system. MATERIALS AND METHODS: We evaluated and combined
      previously described primers and probes for Campylobacter detection, designed a
      new internal amplification control, and optimized the multiplex qPCR for the
      detection of C. jejuni, C. coli, and C. lari. RESULTS: This method was 100%
      specific when tested against a panel of 32 target Campylobacter strains and 31
      non-Campylobacter reference strains. Furthermore, there was no cross-reactivity
      with seven strains from four nontarget Campylobacter species. The amplification
      efficiency of each target in this multiplex qPCR was over 90%, and each
      coefficient of linearity was greater than 0.99. With artificially mixed genomic
      DNA, this method detected as few as two, three, and two genome copies of C.
      jejuni, C. coli, and C. lari, respectively. This method was also able to detect
      these three Campylobacter species in artificially contaminated milk with a
      sensitivity of five spiked cells of each target per reaction. CONCLUSION: The
      three Campylobacter targets were simultaneously identified using artificially
      mixed genomic DNA and spiked raw milk. This SmartCycler-based multiplex qPCR is a
      rapid, specific, and sensitive method to identify C. jejuni, C. coli, and C.
      lari.

PMID- 28440689
TI  - Self-assembled hemoglobin nanoparticles for improved oral photosensitizer
      delivery and oral photothermal therapy in vivo.
AB  - AIM: The aim of the present study was to use hemoglobin (Hb) nanoparticles (NPs)
      to improve oral bioavailability of a near-infrared dye IR780 for in vivo
      antitumor application in photothermal therapy. METHODS: One-step acid-denaturing
      method was used to encapsulate IR780 into self-assembled Hb NPs (IR780@Hb NPs).
      Pharmacokinetics, biodistribution and antitumor effect were studied in vivo.
      RESULTS: The Hb NPs showed high stability in enzymatic and acidic conditions
      similar to the gastric environment, and enhanced absorption of IR780 into the
      blood. In vivo imaging revealed that IR780 could accumulate at the tumor sites
      and effectively caused photothermal effect, which resulted in tumor ablation
      after oral administration in tumor-bearing mice. CONCLUSION: Hb NPs represent a
      promising delivery system for improving oral absorption of photosensitizer dyes,
      which could open new treatment modalities in cancer.

PMID- 28440691
TI  - N-Butyl-2-cyanoacrylate-based injectable and in situ-forming implants for
      efficient intratumoral chemotherapy.
AB  - The local delivery of chemotherapeutic drugs to tumor sites is an effective
      approach for achieving therapeutic drug concentrations in solid tumors.
      Injectable implants with the ability to form in situ represent one of the most
      promising technologies for intratumoral chemotherapy. However, many issues must
      be resolved before these implants can be applied in clinical practice. Herein, we
      report a novel injectable in situ-forming implant system composed of n-butyl-2
      cyanoacrylate (NBCA) and ethyl oleate, and the sol-gel phase transition is
      activated by anions in body fluids or blood. This newly developed injectable NBCA
      ethyl oleate implant (INEI) is biodegradable, biocompatible, and non-toxic. INEI
      solidifies in several seconds after exposure to body fluids or blood, and the
      implant's in vivo degradation time can be controlled. In addition, the pore sizes
      formed by the polymerization of NBCA can be decreased by increasing the NBCA
      concentration in the implants. Therefore, the drug retention/release time can be
      adjusted from a few weeks to several months by changing the concentration of NBCA
      in the implant formulation. Anti-tumor experiments in animal models showed that
      the average growth inhibition rate of xenografted human breast cancer cells by
      the paclitaxel-loaded INEI (40% NBCA) was 80%, and they also indicated that
      tumors in some of the mice were completely eliminated by just a single dosage
      injection. For the epirubicin-loaded INEI (50% NBCA), the average growth
      inhibition rate of xenografted human liver cancer cells was 58%. Thus, the
      chemotherapeutic drug-loaded INEIs exhibited excellent therapeutic efficacy for
      local chemotherapy.

PMID- 28440690
TI  - The chemistries and consequences of DNA and RNA methylation and demethylation.
AB  - Chemical modification of nucleobases plays an important role for the control of
      gene expression on different levels. That includes the modulation of translation
      by modified tRNA-bases or silencing and reactivation of genes by methylation and
      demethylation of cytosine in promoter regions. Especially dynamic methylation of
      adenine and cytosine is essential for cells to adapt to their environment or for
      the development of complex organisms from a single cell. Errors in the cytosine
      methylation pattern are associated with most types of cancer and bacteria use
      methylated nucleobases to resist antibiotics. This Point of View wants to shed
      light on the known and potential chemistry of DNA and RNA methylation and
      demethylation. Understanding the chemistry of these processes on a molecular
      level is the first step towards a deeper knowledge about their regulation and
      function and will help us to find ways how nucleobase methylation can be
      manipulated to treat diseases.

PMID- 28440692
TI  - Both Hepatitis C Virus-Specific T Cell Responses and IL28B rs12979860 Single
      Nucleotide Polymorphism Genotype Influence Antihepatitis C Virus Treatment
      Outcome in Patients with Chronic Hepatitis C.
AB  - Despite new treatments for hepatitis C virus (HCV) infection, IFNalpha-based
      regimens still have clinical relevance in special populations of patients and
      remain the only therapeutic option for many patients. We sought to elucidate the
      interplay between two relevant factors (IL28B polymorphism and T cell immune
      responses) involved in the outcome of this therapy in HCV-infected patients. We
      evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who
      were undergoing a full course of pegIFNalpha/RBV therapy. The interdependence and
      roles of T cell-mediated immune responses and IL28B rs12979860 single-nucleotide
      polymorphism genotype as predictors of virological response to anti-HCV treatment
      in patients with chronic hepatitis C were evaluated using nonparametric tests.
      Factors associated with rapid virological response (RVR) in univariate analysis
      were presence of CD4 T cell response against NS3 HCV protein, low baseline HCV
      RNA, and IL28B CC genotype. Factors associated with sustained virological
      response (SVR) in univariate analysis were IL28B CC genotype, low baseline HCV
      RNA, and presence of CD4 response against NS2. In the multivariate analysis, low
      baseline HCV-RNA and NS3-specific CD4 response showed a clear trend toward
      association with RVR (P = 0.09 and P = 0.07, respectively). Regarding SVR, IL28B
      CC genotype was the strongest predictor (P = 0.02), with presence of NS2-specific
      CD4 response showing a clear trend (P = 0.09). HCV-specific T cell response
      influences the outcome of pegIFNalpha/RBV therapy regardless of IL28B genotype.
      HCV-specific T cell responses (adaptive immunity) seem to influence viral
      clearance both in the short and long term during therapy (RVR and SVR), whereas
      the influence of the IL28B genotype (innate immunity) may be more relevant to the
      long-lasting therapeutic effect (SVR).

PMID- 28440693
TI  - Maternal History of Child Abuse and Obesity Risk in Offspring: Mediation by
      Weight in Pregnancy.
AB  - BACKGROUND: Women's experience of childhood adversity may contribute to their
      children's risk of obesity. Possible causal pathways include higher maternal
      weight and gestational weight gain, which have been associated with both maternal
      childhood adversity and obesity in offspring. METHODS: This study included 6718
      mother-child pairs from the National Longitudinal Survey of Youth 1979 in the
      United States (1979-2012). We applied multiple log-binomial regression models to
      estimate associations between three markers of childhood adversity (physical
      abuse, household alcoholism, and household mental illness) and offspring obesity
      in childhood. We estimated natural direct effects to evaluate mediation by
      prepregnancy BMI and gestational weight gain. RESULTS: Among every 100 mothers
      who reported physical abuse in childhood, there were 3.7 (95% confidence
      interval: -0.1 to 7.5) excess cases of obesity in 2- to 5-year olds compared with
      mothers who did not report physical abuse. Differences in prepregnancy BMI, but
      not gestational weight gain, accounted for 25.7% of these excess cases. There was
      no evidence of a similar relationship for household alcoholism or mental illness
      or for obesity in older children. CONCLUSIONS: In this national, prospective
      cohort study, prepregnancy BMI partially explained an association between
      maternal physical abuse in childhood and obesity in preschool-age children. These
      findings underscore the importance of life-course exposures in the etiology of
      child obesity and the potential multi-generational consequences of child abuse.
      Research is needed to determine whether screening for childhood abuse and
      treatment of its sequelae could strengthen efforts to prevent obesity in mothers
      and their children.

PMID- 28440696
TI  - It's not just heroin anymore.

PMID- 28440695
TI  - Size-variable zone in V3 region of 16S rRNA.
AB  - The size distribution of complete 16S-rRNA sequences from the SILVA-database and
      nucleotide shifts that might interfere with the secondary structure of the
      molecules were evaluated. Overall, 513,309 sequences recorded in SILVA were used
      to estimate the size of hypervariable regions of the gene. Redundant sequences
      were treated as a single sequence to achieve a better representation of the
      molecular diversity. Nucleotides found in each position in 95% of the sequences
      were considered the consensus sequences for different size-groups (consensus95).
      The sizes of different regions ranged from 96.7 to 283.1 nucleotides and had
      similar distribution patterns, except for the V3 region, which exhibited a
      bimodal distribution composed of 2 main peaks of 161 and 186 nt. The alignment of
      Consensuses95 of fractions 161 and 186 showed a high degree of similarity and
      conservation, except for the central positions (gap zone), where the sequence was
      highly variable and several deletions were observed. Structurally, the gap zone
      forms the central part of helix 17 (H17), and its extension was directly
      reflected in the size of this helix. H17 is part of a multihelix conjunction
      known as the 5-way junction (5 WJ), which is indispensable for 30 S ribosome
      assembly. However, because a drastic variation in the sequence size of V3 region
      occurs at a central position in loop H17 without affecting the base of the loop,
      it has no apparent effect on 5 WJ. Finally, considering that these differences
      were detected in non-redundant sequences, it can be concluded that this is not an
      uncommon or isolated event and that the V3 region is possibly more likely to
      mutate than are other regions.

PMID- 28440697
TI  - The prevalence of calcification around odontoid process and the incidence of
      crowned dens syndrome in the neurosurgical ward: A single institution's analysis.
AB  - OBJECTIVE: The objective of this study is to assess the prevalence and natural
      history of odontoid calcification and to identify factors related to its
      progression to crowned dens syndrome (CDS). METHODS: We reviewed a consecutive
      series of patients who underwent head CT upon admission to the neurosurgical ward
      of Niigata Prefectural Shibata Hospital. We evaluated the relationship between
      the presence of odontoid calcification and the patient's age, sex, and primary
      disorder for admission. The incidence of CDS was also determined, and factors
      related to the progression of odontoid calcification to CDS were analyzed.
      RESULTS: Odontoid calcifications were found in 88 out of 554 patients (15.9%)
      undergoing CT scans. Age, female, and stroke were predictive of odontoid
      calcification. The odds ratios (95% CIs) for age, female, and stroke estimated
      from the logistic analysis were 1.084 (1.054-1.114; p < .0001), 1.746 (1.06
      2.875; p = .029), and 1.909 (1.123-3.247; p = .017), respectively. Eleven (12.5%)
      of the 88 patients with odontoid calcification developed CDS. The age, sex, and
      primary disorder for admission were not associated with the onset of CDS.
      CONCLUSIONS: Odontoid calcification is observed incidentally on head CT.
      Clinicians should keep in mind that patients with odontoid calcification might
      develop CDS, even if they are asymptomatic at the time of CT examination.

PMID- 28440698
TI  - Therapeutic PEG-ceramide nanomicelles synergize with salinomycin to target both
      liver cancer cells and cancer stem cells.
AB  - AIM: Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to
      target both liver cancer cells and cancer stem cells. MATERIALS & METHODS: The
      synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the
      antitumor activity of SCM was examined both in vitro and in vivo. RESULTS:
      SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM
      showed superior cytotoxic effect and increased apoptosis-inducing activity in
      both liver cancer cells and cancer stem cells. In vivo, SCM showed the best tumor
      inhibitory effect with a safety profile. CONCLUSION: Thus, PEG-ceramide
      nanomicelles could serve as an effective and safe therapeutic drug carrier to
      deliver SAL into liver cancer, opening up the avenue of using PEG-ceramide as
      therapeutic drug carriers.

PMID- 28440700
TI  - Selection and Assessment of Plant Growth-Promoting Rhizobacteria for Biological
      Control of Multiple Plant Diseases.
AB  - A study was designed to screen individual strains of plant growth-promoting
      rhizobacteria (PGPR) for broad-spectrum disease suppression in vitro and in
      planta. In a preliminary screen, 28 of 196 strains inhibited eight different
      tested pathogens in vitro. In a secondary screen, these 28 strains showed broad
      spectrum antagonistic activity to six different genera of pathogens, and 24 of
      the 28 strains produced five traits reported to be related to plant growth
      promotion, including nitrogen fixation, phosphate solubilization, indole-3-acetic
      acid production, siderophore production, and biofilm formation. In advanced
      screens, the 28 PGPR strains selected in vitro were tested in planta for
      biological control of multiple plant diseases including bacterial spot of tomato
      caused by Xanthomonas axonopodis pv. vesicatoria, bacterial speck of tomato
      caused by Pseudomonas syringae pv. tomato, damping-off of pepper caused by
      Rhizoctonia solani, and damping-off of cucumber caused by Pythium ultimum. In
      all, 5 of the 28 tested strains significantly reduced three of the four tested
      diseases, and another 19 strains showed biological control to two tested
      diseases. To understand the observed broad-spectrum biocontrol capacity,
      antiSMASH was used to predict secondary metabolite clusters of selected strains.
      Multiple gene clusters encoding for secondary metabolites, e.g., bacillibactin,
      bacilysin, and microcin, were detected in each strain. In conclusion, selected
      individual PGPR strains showed broad-spectrum biocontrol activity to multiple
      plant diseases.

PMID- 28440701
TI  - Yeast capsules for targeted delivery: the future of nanotherapy?

PMID- 28440699
TI  - Effect of treatments for depression on quality of life: a meta-analysis.
AB  - Cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors
      (SSRIs) are the two first-line treatments for depression, but little is known
      about their effects on quality of life (QOL). A meta-analysis was conducted to
      examine changes in QOL in adults with major depressive disorder who received CBT
      (24 studies examining 1969 patients) or SSRI treatment (13 studies examining 4286
      patients) for their depression. Moderate improvements in QOL from pre to post
      treatment were observed in both CBT (Hedges' g = .63) and SSRI (Hedges' g = .79)
      treatments. The effect size remained stable over the course of the follow-up
      period for CBT. No data were available to examine follow-ups in the SSRI group.
      QOL effect sizes decreased linearly with publication year, and greater
      improvements in depression were significantly associated with greater
      improvements in QOL for CBT, but not for SSRIs. CBT and SSRIs for depression were
      both associated with moderate improvements in QOL, but are possibly caused by
      different mechanisms.

PMID- 28440703
TI  - Zeta-potential-changing nanoparticles conjugated with cell-penetrating peptides
      for enhanced transfection efficiency.
AB  - AIM: The aim of this study was to develop zeta-potential-changing nanoparticles
      (NPs) combining cell-penetrating peptides for gene delivery. METHODS & MATERIALS:
      NPs were formed using phosphorylated carboxymethyl cellulose-glucosamine 6
      phosphate (CMC-G6P) and polyethylene imine-polyarginine conjugates. Phosphate
      release was evaluated using intestinal alkaline phosphatase and cell lines.
      Transfection studies with plasmid DNA were then performed. RESULTS: The zeta
      potential of CMC-G6P/branched PEI NPs was -3 mV and switched to +4 mV after
      intestinal alkaline phosphatase cleavage. The released phosphate in human colon
      adenocarcinoma cell line was more pronounced than human embryonic kidney cell
      line 293. Transfection studies demonstrated the greatest expression of plasmid
      DNA when being incorporated into CMC-G6P/polyethylene imine-polyarginine NPs.
      CONCLUSION: Novel zeta potential changing NPs combining cell-penetrating peptides
      are a promising tool to deliver DNA drugs to target cells.

PMID- 28440705
TI  - Biodegradable inorganic nanoparticles: an opportunity for improved cancer
      therapy?

PMID- 28440706
TI  - Agency and communion in people with Alzheimer's disease, as described by
      themselves and their spousal carers.
AB  - Agency (individuality) and communion (togetherness) are vital to a positive sense
      of self. People with Alzheimer's disease are at risk of experiencing diminished
      agency and decreased communion. Their family members', especially their
      partner's, view on their agency and communion is also likely to influence their
      sense of agency, communion, and self. In the present study, individual interviews
      with 10 people with Alzheimer's disease and their spousal carers were
      qualitatively analysed to describe how in each couple the two spouses viewed the
      agency and communion of the person with Alzheimer's disease from an individual
      perspective. The findings show that the carers generally described the agency of
      the person with Alzheimer's disease as slightly weaker compared with the persons
      with Alzheimer's disease themselves. The carers also appeared to have poor
      knowledge of what supported and threatened the sense of communion of the person
      with Alzheimer's disease.

PMID- 28440704
TI  - Effect of femoral head size and surgical approach on risk of revision for
      dislocation after total hip arthroplasty.
AB  - Background and purpose - Recurrent dislocation is the commonest cause of early
      revision of a total hip arthropasty (THA). We examined the effect of femoral head
      size and surgical approach on revision rate for dislocation, and for other
      reasons, after total hip arthroplasty (THA). Patients and methods - We analyzed
      data on 166,231 primary THAs and 3,754 subsequent revision THAs performed between
      2007 and 2015, registered in the Dutch Arthroplasty Register (LROI). Revision
      rate for dislocation, and for all other causes, were calculated by competing-risk
      analysis at 6-year follow-up. Multivariable Cox proportional hazard regression
      ratios (HRs) were used for comparisons. Results - Posterolateral approach was
      associated with higher dislocation revision risk (HR =1) than straight lateral,
      anterolateral, and anterior approaches (HR =0.5-0.6). However, the risk of
      revision for all other reasons (especially stem loosening) was higher with
      anterior and anterolateral approaches (HR =1.2) and lowest with posterolateral
      approach (HR =1). For all approaches, 32-mm heads reduced the risk of revision
      for dislocation compared to 22- to 28-mm heads (HR =1 and 1.6, respectively),
      while the risk of revision for other causes remained unchanged. 36-mm heads
      increasingly reduced the risk of revision for dislocation but only with the
      posterolateral approach (HR =0.6), while the risk of revision for other reasons
      was unchanged. With the anterior approach, 36-mm heads increased the risk of
      revision for other reasons (HR =1.5). Interpretation - Compared to the
      posterolateral approach, direct anterior and anterolateral approaches reduce the
      risk of revision for dislocation, but at the cost of more stem revisions and
      other revisions. For all approaches, there is benefit in using 32-mm heads
      instead of 22- to 28-mm heads. For the posterolateral approach, 36-mm heads can
      safely further reduce the risk of revision for dislocation.

PMID- 28440707
TI  - Recent developments in nanocarrier-aided mucosal vaccination.
AB  - To date, most of the licensed vaccines for mucosal delivery are based on live
      attenuated viruses which carry the risk of regaining their pathogenicity.
      Therefore, the development of efficient nonviral vectors allowing the induction
      of potent humoral and cell-mediated immunity is regarded as an imperative
      scientific challenge as well as a commercial breakthrough for the pharma
      industries. For a successful translation to the clinic, such nanocarriers should
      protect the antigens from mucosal enzymes, facilitate antigen uptake by microfold
      cells and allow the copresentation of robust, safe for human use, mucosal
      adjuvants to antigen-presenting cells. Finally, the developed formulations should
      exhibit accuracy regarding the administered dose, a major drawback of mucosal
      vaccines in comparison with parenteral ones.

PMID- 28440708
TI  - Toward in vitro-to-in vivo translation of monoclonal antibody pharmacokinetics:
      Application of a neonatal Fc receptor-mediated transcytosis assay to understand
      the interplaying clearance mechanisms.
AB  - Monoclonal antibodies (mAbs) are a rapidly growing drug class for which great
      efforts have been made to optimize certain molecular features to achieve the
      desired pharmacokinetic (PK) properties. One approach is to engineer the
      interactions of the mAb with the neonatal Fc receptor (FcRn) by introducing
      specific amino acid sequence mutations, and to assess their effect on the PK
      profile with in vivo studies. Indeed, FcRn protects mAbs from intracellular
      degradation, thereby prolongs antibody circulation time in plasma and modulates
      its systemic clearance. To allow more efficient and focused mAb optimization, in
      vitro input that helps to identify and quantitatively predict the contribution of
      different processes driving non-target mediated mAb clearance in vivo and
      supporting translational PK modeling activities is essential. With this aim, we
      evaluated the applicability and in vivo-relevance of an in vitro cellular FcRn
      mediated transcytosis assay to explain the PK behavior of 25 mAbs in rat or
      monkey. The assay was able to capture species-specific differences in IgG-FcRn
      interactions and overall correctly ranked Fc mutants according to their in vivo
      clearance. However, it could not explain the PK behavior of all tested IgGs,
      indicating that mAb disposition in vivo is a complex interplay of additional
      processes besides the FcRn interaction. Overall, the transcytosis assay was
      considered suitable to rank mAb candidates for their FcRn-mediated clearance
      component before extensive in vivo testing, and represents a first step toward a
      multi-factorial in vivo clearance prediction approach based on in vitro data.

PMID- 28440709
TI  - The relationship between attachment style and placement of parents in adults'
      attachment networks over time.
AB  - Using a bull's-eye hierarchical mapping technique (HMT), the present study
      examined placement of parents in adults' attachment networks over time. We
      hypothesized that attachment style would predict distance at which network
      members (mother, father, and romantic partner) would be placed from the core-self
      over time. Participants completed the HMT on two occasions, 12 months apart.
      Concurrently and over time, fathers were placed further from the core-self than
      mothers. Attachment style explained unique variance, beyond that accounted for by
      individual and relationship characteristics. Specifically, network members with
      whom participants reported greater attachment insecurity were placed further from
      the core-self concurrently. Mothers with whom participants reported greater
      attachment insecurity were placed further from the core-self over time.
      Unsatisfactory attachment relationships with father and partner and those marked
      by higher attachment insecurity were more likely to be excluded from attachment
      networks over time. Findings suggest that attachment style, relationship quality,
      romantic relationship status, and parents' marital status determine the placement
      of parents in adults' attachment networks.

PMID- 28440710
TI  - Selenium nanoparticles: potential in cancer gene and drug delivery.
AB  - In recent decades, colloidal selenium nanoparticles have emerged as exceptional
      selenium species with reported chemopreventative and therapeutic properties. This
      has sparked widespread interest in their use as a carrier of therapeutic agents
      with results displaying synergistic effects of selenium with its therapeutic
      cargo and improved anticancer activity. Functionalization remains a critical step
      in selenium nanoparticles' development for application in gene or drug delivery.
      In this review, we highlight recent developments in the synthesis and
      functionalization strategies of selenium nanoparticles used in cancer drug and
      gene delivery systems. We also provide an update of recent preclinical studies
      utilizing selenium nanoparticles in cancer therapeutics.

PMID- 28440711
TI  - Carrying their own weight: Dogs perceive changing affordances for reaching.
AB  - Choices about when to transition between two modes of behaviour are determined by
      the fit between action capabilities and environmental properties. However, such
      transitions typically occur not at the absolute limits of action capabilities but
      rather based on the relative stability of each mode. People transition from an
      arm-only to an arm-plus-torso-reach, not when object distance exceeds arm length
      but when the stability of reaching with the arm-plus-torso exceeds that of
      reaching with the arm-only. To the extent that perception is supported by
      detection of invariant stimulation patterns, such a transition ought to reflect
      both the fit between action capabilities and environmental properties and the
      relative stability of modes regardless of species. We investigated the height at
      which dogs transitioned from reaching with the head-only to rearing when wearing
      a weighted backpack - a manipulation expected to decrease the stability of a head
      only reach. As expected, the transition occurred at taller heights for tall than
      for short dogs but at the same ratio of treat-height-to-shoulder-height for both
      groups. This transition also occurred at shorter heights and smaller ratios of
      treat-height-to-shoulder-height when dogs wore a weighted backpack. The results
      suggest that stimulation patterns that support control of behaviour may be
      invariant across species.

PMID- 28440712
TI  - Gelatin-albumin hybrid nanoparticles as matrix metalloproteinases-degradable
      delivery systems for breast cancer therapy.
AB  - AIM: To develop matrix metalloproteinase-responsive gelatin-albumin hybrid
      nanoparticles encapsulating a selective tropomyosin receptor kinase A (TrkA)
      inhibitor GNF-5837 (Gel-Alb-GNF HNPs) and to demonstrate their anticancer effects
      in breast cancer. METHODS: Gel-Alb-GNF HNPs were prepared using a pH-controlled
      complexation process from cationic gelatin, dextran sulfate and albumin-bound GNF
      5837. The anticancer activities of Gel-Alb-GNF HNPs were tested in a panel of
      subtype-specific breast cancer cell lines. RESULTS: Gel-Alb-GNF HNPs (~130 nm)
      displayed excellent stability and matrix metalloproteinase-triggered drug
      release. Compared with GNF-5837 alone, Gel-Alb-GNF HNPs not only significantly
      enhanced the antiproliferative and anti-invasive effects but also restored the
      apoptosis of cancer cells. CONCLUSION: Gel-Alb-GNF HNPs may be adaptable for
      stand-alone therapies or used in combination with traditional chemotherapies for
      breast cancer treatment.

PMID- 28440713
TI  - Glycinated fullerenes for tamoxifen intracellular delivery with improved
      anticancer activity and pharmacokinetics.
AB  - AIM: Glycine-tethered C60-fullerenes were conjugated with N-desmethyl tamoxifen
      and evaluated for drug delivery benefits. MATERIALS & METHODS: C60-fullerenes
      were functionalized with glycine, and N-desmethyl tamoxifen was conjugated,
      employing a linker and characterized for micromeritics, drug loading, drug
      release and evaluated for cancer cell toxicity, cellular uptake and
      pharmacokinetics. RESULTS: The nanoconjugate with a drug entrapment efficiency of
      82.71 +/- 6.23% and a drug loading of 66.01 +/- 4.98% was hemocompatibile with
      appreciable MCF-7 cytotoxicity. The confocal results confirmed enhanced uptake of
      conjugate. Interestingly, pharmacokinetic outcomes of the conjugate were superior
      and the area under the curve was enhanced by approximately three-times, whereas
      the drug clearance was reduced by around five-times, after single intravenous
      injection. CONCLUSION: The conjugation assured improved availability of drug in a
      biological system for prolonged duration as well as in the interiors of target
      cells with a promise of enhanced efficacy and compatibility.

PMID- 28440714
TI  - Hypereosinophilic syndrome: endomyocardial biopsy versus echocardiography to
      diagnose cardiac involvement.
AB  - OBJECTIVE: To compare echocardiograms and endomyocardial biopsies to diagnose
      cardiac involvement in hypereosinophilic syndrome. METHODS: We examined the
      agreement between echocardiography and endomyocardial biopsies to detect cardiac
      involvement in hypereosinophilic syndrome by reviewing cases identified as
      hypereosinophilia or hypereosinophilic syndrome in Mayo Clinic databases from
      January 1978 through June 2009. Single-organ cases of eosinophilia such as
      eosinophilic fasciitis and eosinophilic gastroenteritis were excluded. We
      recorded echocardiogram and endomyocardial biopsy results including biopsy
      staining for eosinophil granule major basic protein (if performed). Clinical and
      laboratory features documented included presenting symptom(s), maximum total
      eosinophil count, dose of prednisone (if any) and eosinophil count at the time of
      endomyocardial biopsy, cardiac enzymes, serum tryptase level, electrocardiogram
      result, the result of testing for the FIP1L1-PDGFRA fusion gene, complications
      associated with the biopsy procedures and available follow-up information.
      RESULTS: From a total of 387 patients' records screened 288 met the criteria for
      hypereosinophilic syndrome and of these 240 had echocardiograms. Among these
      patients there were 138 normal echocardiograms, 67 had echocardiograms without
      findings of hypereosinophilic syndrome but with one or more other abnormalities,
      and 35 had echocardiograms with findings consistent with hypereosinophilic
      syndrome. Twenty-five patients from this group of 35 patients had both
      echocardiogram and endomyocardial biopsy. In 15 patients there was agreement
      between both endomyocardial biopsy and echocardiography as to the presence (n =
      seven) or absence (n = eight) for findings of cardiac involvement. In 10 of 25
      patients test results diverged: 3 patients with positive echocardiographic
      changes did not have confirmatory findings by endomyocardial biopsy and seven
      patients with positive biopsy findings had echocardiograms without findings of
      hypereosinophilic syndrome. CONCLUSIONS: Echocardiograms and endomyocardial
      biopsies agree for presence or absence of cardiac involvement 60% of the time.
      Endomyocardial biopsy detected cardiac involvement in 7 patients in whom the
      echocardiogram was negative for findings of hypereosinophilic syndrome.

PMID- 28440715
TI  - GnRH-agonist triggering for final oocyte maturation in GnRH-antagonist IVF cycles
      induces decreased LH pulse rate and amplitude in early luteal phase: a possible
      luteolysis mechanism.
AB  - The use of GnRH agonist to trigger final oocyte maturation in GnRH-antagonist in
      vitro fertilization (IVF) cycles has been shown to significantly reduce or even
      eliminate the risk of ovarian hyperstimulation syndrome (OHSS) by inducing rapid
      luteolysis early in the luteal phase. The exact mechanism of this early
      luteolysis is still widely unknown. Since luteinizing hormone (LH) has a major
      role in corpus luteum support, we sought to explore the pattern of LH secretion
      early in the luteal phase. Ten high risk patients for developing OHSS and
      triggered with GnRH agonist were included. Frequent blood sampling (every 20 min
      for 6 h) to measure LH, estradiol and progesterone was done on the day of oocyte
      collection (n = 5, Group 1) and on the day of embryo transfer, 48 h after oocyte
      collection (n = 5, Group 2). We found that the mean LH concentration and its
      secretion rate decreased significantly in Group 2 compared to Group 1. Both
      groups had similar number of LH pulses characterized by very small amplitude. In
      Group 2, there was a steady significant decrease in estradiol and progesterone
      over time. The results of this study show that LH secretion deviates
      significantly from normal physiologic pattern, which can explain, at least in
      part, the post-GnRH-agonist trigger early luteolysis mechanism.

PMID- 28440716
TI  - Exercise reduced pentraxin 3 levels produced by endotoxin-stimulated human
      peripheral blood mononuclear cells in obese individuals.
AB  - The purpose of this study was to determine whether obesity would reduce the
      capacity of peripheral blood mononuclear cells (PBMCs) to produce the anti
      inflammatory protein pentraxin 3 (PTX3) in response to ex vivo stimulation with
      lipopolysaccharide (LPS), and if acute aerobic exercise would enhance this PTX3
      production capacity. In addition, the inter-relationships of LPS-induced PTX3
      with the inflammatory cytokines (interleukin 6 [IL-6], IL-10, and tumor necrosis
      factor alpha) were examined. Twenty-one healthy subjects (10 obese and 11 normal
      weight) performed an acute bout of aerobic exercise at 75% VO2max. The capacity
      of PBMCs to produce PTX3 ex vivo following LPS stimulation was the same in obese
      and normal-weight subjects at rest, and decreased equally in both subject groups
      following acute aerobic exercise. This is in contrast to plasma PTX3, which is
      lower in obese subjects at rest and increased equally in both obese and normal
      weight subjects following exercise. In addition, ex vivo PTX3 production was
      positively associated with IL-6 and IL-10 in response to acute aerobic exercise (
      r = 0.686, P = 0.020; r = 0.744, P = 0.009, respectively) in normal-weight, but
      not in obese individuals ( r = 0.429, P = 0.249; r = 0.453, P = 0.189,
      respectively). These findings indicate that concentrations of PTX3 observed in
      plasma are relatively independent of those produced by PBMCs ex vivo and the
      mechanisms associated with PTX3-mediated anti-inflammatory signaling may differ
      during obesity. Impact statement Our laboratory has previously demonstrated that
      obese individuals present with lower plasma concentrations of the anti
      inflammatory protein pentraxin 3 (PTX3), whereas acute aerobic exercise increases
      plasma PTX3 levels similarly compared to normal-weight individuals. As a follow
      up, the present study demonstrates that PBMCs isolated from obese and normal
      weight individuals produce comparable amounts of PTX3 ex vivo in response to
      lipopolysaccharide (LPS). Furthermore, given that acute aerobic exercise reduced
      the ex vivo production of PTX3 in both groups, our results clearly indicate that
      plasma PTX3 levels are relatively independent of those produced by PBMCs ex vivo.
      In addition, our findings suggest that the mechanisms associated with PTX3
      mediated production of the anti-inflammatory cytokine interleukin 10 may be
      impaired in obese individuals, and thus provides a key finding necessary for the
      elucidation of PTX3's role in the mediation of anti-inflammatory profiles and the
      subsequent amelioration of inflammatory disease during obesity.

PMID- 28440717
TI  - Serum carotenoid interactions in premenopausal women reveal alpha-carotene is
      negatively impacted by body fat.
AB  - Increasing body mass indices (BMIs) across the globe reflect pandemic shifts
      towards habitual positive energy imbalances. Excess body fat in individuals is
      often associated with high-energy and high-fat diets scanty in fresh produce.
      Carotenoids are fat-soluble pigments plentiful in many fruits and vegetables.
      They are well-known for provitamin A and antioxidant functions, but little
      research has been done related to carotenoid-body mass interactions. Serum
      carotenoids were analyzed relative to body fat to determine correlations between
      major serum carotenoids, retinol, BMI, fat mass, and lean mass. Healthy women ( n
      = 76), 19-50 years old, were categorized into two comparison groups determined by
      percent body fat measured by air displacement plethysomography (BOD POD(r)), i.e.
      <31% and >=31% fat mass. Anthropometric and three-day diet records were completed
      for BMI and nutrient intake calculations, respectively. Serum alpha-carotene
      concentrations were strongly inversely associated with all measures of body
      composition ( P < 0.001 alpha-carotene) controlling for dietary intake and age,
      while beta-carotene, lutein, and lycopene were not ( P > 0.05). Dietary intake
      between groups did not differ, including carrot consumption (a high dietary
      source of alpha-carotene). These results confirm previous carotenoid-health
      research and propose the need for further investigation of potential protective
      roles that alpha-carotene may perform for optimal health. Serum alpha-carotene
      may provide a deeper and clinically relevant purpose, beyond previous suggestions
      for its use as a biomarker for fruit and vegetable consumption, in that alpha
      carotene may be a biomarker for chronic disease risk frequently linked with
      obesity. Impact statement Carotenoids are important pigments in fruit and
      vegetables and found in human serum. This study isolated a negative relationship
      between serum alpha-carotene and body fatness. As humans begin to live over a
      century, determining biomarkers of ultimate health is important. alpha-Carotene
      does not have the same distribution in the food supply as beta-carotene and
      therefore is often overlooked in surveys. In part, this is due to the fact that
      beta-carotene provides two molecules of vitamin A, while alpha-carotene provides
      one upon central cleavage. This study shows a very clear association between
      alpha-carotene and body fatness, which appears to go beyond its fat-soluble
      nature. Dietary intake data were not able to explain the association. Further
      work is needed to determine what dietary components infer health benefits.

PMID- 28440718
TI  - Problematizing the concept of the "borderline" group in performance assessments.
AB  - INTRODUCTION: Many standard setting procedures focus on the performance of the
      "borderline" group, defined through expert judgments by assessors. In performance
      assessments such as Objective Structured Clinical Examinations (OSCEs), these
      judgments usually apply at the station level. METHODS AND RESULTS: Using largely
      descriptive approaches, we analyze the assessment profile of OSCE candidates at
      the end of a five year undergraduate medical degree program to investigate the
      consistency of the borderline group across stations. We look specifically at
      those candidates who are borderline in individual stations, and in the overall
      assessment. While the borderline group can be clearly defined at the individual
      station level, our key finding is that the membership of this group varies
      considerably across stations. DISCUSSION AND CONCLUSIONS: These findings pose
      challenges for some standard setting methods, particularly the borderline group
      and objective borderline methods. They also suggest that institutions should
      ensure appropriate conjunctive rules to limit compensation in performance between
      stations to maximize "diagnostic accuracy". In addition, this work highlights a
      key benefit of sequential testing formats in OSCEs. In comparison with a
      traditional, single-test format, sequential models allow assessment of
      "borderline" candidates across a wider range of content areas with concomitant
      improvements in pass/fail decision-making.

PMID- 28440719
TI  - A case-based medical curriculum for the 21st century: The use of innovative
      approaches in designing and developing a case on mental health.
AB  - The introduction of case-based learning (CBL) by the School of Medicine at
      Cardiff University has encouraged innovation in medical teaching and learning.
      During years one and two of the modernized MBBCh program, students complete 17
      cases as part of the newly developed C21 curriculum that emphasizes a patient
      oriented and student-centered approach to learning. The mental health case, which
      is presented in year 2, incorporates a number of novel teaching resources that
      aim to enhance the students' learning experience and to further reinforce the
      patient-oriented and community-based philosophy of C21. These include the use of
      fictionalized video diaries, virtual patient cases, e-learning workbooks, an
      interactive practical session, and community placements. Novel teaching methods
      and resources were evaluated by students in terms of effectiveness and value as
      learning resources through the administration of a structured mixed
      questionnaire. The results revealed that students valued the inclusion of these
      resources, which they evaluated as having contributed to their understanding of
      the subject area. Furthermore, the case was found to have had an impact on
      student interest in psychiatry as a specialty as well as a career choice. The
      positive student evaluation of this case supports the innovations in teaching
      delivery inspired by C21.

PMID- 28440720
TI  - The reliability of assessments: The Bayesian Cronbach's alpha.

PMID- 28440721
TI  - Twelve tips for promoting learning during presentations in cross cultural
      settings.
AB  - Educators frequently learn together in cross cultural settings such as at
      international conferences. Cultural differences should influence how educational
      programs are designed and delivered to effectively support learning; cultural
      sensitivity and the competence to deal with such differences are important skills
      for health professions educators. Teaching without this approach may lead to lost
      learning opportunities. This article provides twelve tips for educators to
      consider when planning and delivering formal presentations (e.g. lectures and
      workshops) in cross cultural settings. The tips were constructed based on a
      literature review, the authors' experience, and interviews with international
      educators who frequently deliver and receive education in cross cultural
      settings. The tips are divided into three phases: (1) preparation for the session
      to optimize learners' experience (2) interaction when delivering the session and
      (3) reflection on the experience.

PMID- 28440722
TI  - Twelve tips for teaching about patients with cognitive impairment.
AB  - The global population is ageing and consequently cognitive problems are
      increasingly prevalent. To ensure that the healthcare needs of this complex group
      are met, healthcare professionals must receive adequate training in this field.
      There are, however, a variety of reasons why this is not currently being
      achieved, including, but not limited to: ethical and logistical issues relating
      to the delivery of educational experiences involving cognitively impaired
      patients; a failure of curricula to keep pace with the changing demographic;
      societal and institutional ageism; and the inherent complexity of the conditions.
      This article highlights challenges associated with the delivery of such training
      to medical undergraduates and presents strategies to tackle these. Drawing on
      current evidence where available, the 12 tips below offer educators practical
      advice on how to maximize the value of medical undergraduates' educational
      experiences with cognitively impaired patients.

PMID- 28440723
TI  - Almost everything is the realm of the rich!

PMID- 28440725
TI  - Top-rated AMEE MedEdPublish Papers - January 2017.

PMID- 28440724
TI  - Medical Teacher in Ten Minutes.

PMID- 28440726
TI  - Expression of C-type lectin receptor mRNA in chronic otitis media with
      cholesteatoma.
AB  - CONCLUSIONS: The levels of expression of various C-type lectin receptors (CLRs)
      messenger ribo nucleic acids (mRNAs) were significantly higher in cholesteatomas
      than in normal skin, suggesting that these CLRs may be involved in the
      pathogenesis of cholesteatoma. OBJECTIVES: Altered expression of pattern
      recognition receptors may be associated with immune responses in patients with
      cholesteatoma. This study assessed the levels of expression of CLR mRNAs in
      normal skin and in cholesteatoma. METHODS: Cholesteatoma specimens were obtained
      from 38 patients with acquired cholesteatoma. The levels of expression of various
      CLR mRNAs were assessed quantitatively using real-time RT-PCR (Reverse
      transcription polymerase chain reaction) and correlated with age, sex, the
      presence of bacteria, hearing level, frequency of surgery, and degree of ossicle
      destruction. RESULTS: The levels of CD206 (cluster of differentiation 206), DEC
      205 (Dendritic and epithelial cell-205), MGL (monoacylglycerol lipase), CLEC5A (C
      type lectin domain family 5 member A), Dectin-2 (dendrite cell-associated C-type
      lectin-2), BDCA2 (Blood dendritic cell antigen 2), Mincle, DCIR (dendritic cell
      immunoreceptor), Dectin-1, MICL (Myeloid inhibitory C type-like lectin), and
      CLEC12B (C-type lectin domain family 12, member B) mRNAs were significantly
      higher in cholesteatoma than in control skin samples (p < 0.05). The levels of
      CLEC5A (C-type lectin domain family 5 member) and Dectin-1 mRNAs were
      significantly higher in cholesteatomas with >=2 than <=1 destroyed ossicles (p <
      0.05), and the levels of MGL, Mincle, Dectin-1, and CLEC12B mRNAs were
      significantly higher in recurrent than initial cholesteatoma specimens (p <
      0.05). The level of CLEC5A mRNAs was significantly higher in patients with severe
      than mild-to-moderate hearing loss (p < 0.05).

PMID- 28440727
TI  - Foam sclerotherapy of the great saphenous vein in association with pre-terminal
      saphenous junction ligation/division as an office-based procedure: 12-Month
      results.
AB  - Objective Ultrasound-guided foam sclerotherapy (UGFS) - one of the most
      frequently recommended methods for treating great saphenous vein incompetence -
      is easy and inexpensive. However, it achieves a lower occlusion rate compared to
      endovenous thermal ablation. The application of UGFS to pre-terminal great
      saphenous vein interruption, eliminating the saphenous stem wash out effect,
      enhances the short-term occlusion rate. This study explores the results of this
      technique at 12 months. Method Thirty great saphenous veins (28 patients) with
      junction incompetence, with calibres >6 mm and >30 cm reflux stem length were
      submitted to echo-guided pre-terminal great saphenous vein interruption and foam
      great saphenous vein occlusion. Participants were subjected to a 12-month post
      operative review by ultrasound assessment of great saphenous vein occlusion and
      terminal stump stability. Comparisons were made between pre-operative and 12
      month Validation of Venous Clinical Severity Score (VCSS), photopletismography,
      Aberdeen questionnaire and complications. Results After 12 months, 28/30 great
      saphenous veins remained occluded (93%). One complete and one partial
      recanalization did not require retreatment. Four saphenous stumps showed a reflux
      during Valsalva (one due to recanalization, one limited to the stump, two with
      reflux in the anterior accessory saphenous vein). VCSS improved from 3.33 +/-
      1.64 to 0.67 +/- 1.21 ( p < 0.05). Aberdeen questionnaire scores decreased from
      9.44 +/- 6.18 to 2.47 +/- 3.77 ( p < 0.05). For photopletismographic examination,
      the mean venous refilling time (normal value: > 25 s) improved from 17.94 +/-
      11.97 to 31.4 +/- 11.99 ( p < 0.05). Conclusion Applying pre-terminal great
      saphenous vein interruption to UGFS of the saphenous stem achieved an occlusion
      rate at one year similar to that of endovenous thermal ablation. The procedure is
      simple, effective, office based, and may be used as a 10-min prolongation to a
      phlebectomy.

PMID- 28440728
TI  - Characterization of chemical contaminants generated by a desktop fused deposition
      modeling 3-dimensional Printer.
AB  - Printing devices are known to emit chemicals into the indoor atmosphere.
      Understanding factors that influence release of chemical contaminants from
      printers is necessary to develop effective exposure assessment and control
      strategies. In this study, a desktop fused deposition modeling (FDM) 3
      dimensional (3-D) printer using acrylonitrile butadiene styrene (ABS) or
      polylactic acid (PLA) filaments and two monochrome laser printers were evaluated
      in a 0.5 m3 chamber. During printing, chamber air was monitored for vapors using
      a real-time photoionization detector (results expressed as isobutylene
      equivalents) to measure total volatile organic compound (TVOC) concentrations,
      evacuated canisters to identify specific VOCs by off-line gas chromatography-mass
      spectrometry (GC-MS) analysis, and liquid bubblers to identify carbonyl compounds
      by GC-MS. Airborne particles were collected on filters for off-line analysis
      using scanning electron microscopy with an energy dispersive x-ray detector to
      identify elemental constituents. For 3-D printing, TVOC emission rates were
      influenced by a printer malfunction, filament type, and to a lesser extent, by
      filament color; however, rates were not influenced by the number of printer
      nozzles used or the manufacturer's provided cover. TVOC emission rates were
      significantly lower for the 3-D printer (49-3552 ug h-1) compared to the laser
      printers (5782-7735 ug h-1). A total of 14 VOCs were identified during 3-D
      printing that were not present during laser printing. 3-D printed objects
      continued to off-gas styrene, indicating potential for continued exposure after
      the print job is completed. Carbonyl reaction products were likely formed from
      emissions of the 3-D printer, including 4-oxopentanal. Ultrafine particles
      generated by the 3-D printer using ABS and a laser printer contained chromium.
      Consideration of the factors that influenced the release of chemical contaminants
      (including known and suspected asthmagens such as styrene and 4-oxopentanal) from
      a FDM 3-D printer should be made when designing exposure assessment and control
      strategies.

PMID- 28440729
TI  - 2-Arachidonoylglycerol endocannabinoid signaling coupled to metabotropic
      glutamate receptor type-5 modulates anxiety-like behavior in the rat ventromedial
      prefrontal cortex.
AB  - 2-Arachidonoylglycerol and anandamide are the main endocannabinoids, which act
      through cannabinoid type-1 and type-2 receptors. Among its many functions,
      anandamide modulates anxiety-like behaviors in the ventromedial prefrontal
      cortex. The role of 2-arachidonoylglycerol in this region, however, has remained
      unclear. Here, we verified whether intra- ventromedial prefrontal cortex
      injection of 2-arachidonoylglycerol or URB602, a monoacylglycerol lipase
      inhibitor (responsible for 2-arachidonoylglycerol hydrolysis), induce anxiolytic
      like effects in Wistar rats. Since activation of metabotropic glutamate receptor
      type 5 promotes diacylglycerol lipase-alpha-mediated 2-arachidonoylglycerol
      synthesis, we also verified if the blockade of this receptor impairs the
      anxiolytic-like effect induced by URB 602. 2-Arachidonoylglycerol reduced anxiety
      like response in rats exposed to the Elevated Plus Maze test, an effect mimicked
      by URB602. Cannabinoid type-1 and type-2 receptor antagonists prevented these
      effects. The pre-treatment with an ineffective dose of MPEP, a metabotropic
      glutamate receptor type 5 antagonist, also attenuated the anxiolytic-like effect
      of URB602. Moreover, immunofluorescence microscopy revealed co-expression of
      metabotropic glutamate receptor type 5 and diacylglycerol lipase-alpha in several
      neurons in slices from the ventromedial prefrontal cortex. Altogether, our
      results implicate 2-arachidonoylglycerol and both cannabinoid receptors on
      anxiety-related behaviors mediated by ventromedial prefrontal cortex. Further,
      these data support a role for the coupling between metabotropic glutamate
      receptor type 5 activation and 2-arachidonoylglycerol signalling as a mechanism
      modulating aversive responses.

PMID- 28440730
TI  - Inspiratory capacity is not altered in operable chronic thromboembolic pulmonary
      hypertension.
AB  - Pathological alterations of inspiratory capacity (IC) have been observed in
      pulmonary hypertension. However, the clinical significance of IC in operable
      chronic thromboembolic pulmonary hypertension (CTEPH) without other pulmonary
      diseases remains unknown. CTEPH patients scheduled for pulmonary endarterectomy
      were prospectively screened. Despite being associated with functional capacity,
      pathological alterations of IC were not observed.

PMID- 28440731
TI  - Pulmonary venous remodeling in COPD-pulmonary hypertension and idiopathic
      pulmonary arterial hypertension.
AB  - Pulmonary vascular arterial remodeling is an integral and well-understood
      component of pulmonary hypertension (PH). In contrast, morphological alterations
      of pulmonary veins in PH are scarcely described. Explanted lungs (n = 101) from
      transplant recipients with advanced chronic obstructive pulmonary disease (COPD)
      and idiopathic pulmonary arterial hypertension (IPAH) were analyzed for venous
      vascular involvement according to a pre-specified, semi-quantitative grading
      scheme, which categorizes the intensity of venous remodeling in three groups of
      incremental severity: venous hypertensive (VH) grade 0 = characterized by an
      absence of venous vascular remodeling; VH grade 1 = defined by a dominance of
      either arterialization or intimal fibrosis; and VH grade 2 = a substantial
      composite of arterialization and intimal fibrosis. Patients were grouped
      according to clinical and hemodynamic characteristics in three groups: COPD non
      PH, COPD-PH, and IPAH, respectively. Histological specimens were examined by a
      cardiovascular pathologist blinded to clinical and hemodynamic data. Pathological
      alterations of pulmonary veins were present in all hemodynamic groups, with the
      following incidences of VH grade 0/1/2: 34/66/0% in COPD non-PH; 19/71/10% in
      COPD-PH; and 11/61/28% in IPAH. In COPD, explorative correlation analysis of
      venous remodeling suggested a modest positive correlation with systolic and mean
      pulmonary artery pressure ( P = 0.032, respectively) and an inverse modest
      correlation with diffusion capacity for carbon monoxide ( P = 0.027). In
      addition, venous remodeling correlated positively with the degree of arterial
      remodeling ( P = 0.014). In COPD-PH and IPAH, advanced forms of pulmonary venous
      remodeling are present, emphasizing that the disease is not exclusively
      restricted to arterial lesions. In addition, venous remodeling may be related to
      the hemodynamic severity, but more rigorous analysis is required to clearly
      define potential relationships.

PMID- 28440732
TI  - Expression of microRNA let-7a positively correlates with hepatitis B virus
      replication in hepatocellular carcinoma tissues.
AB  - Let-7a miRNA is downregulated in various cancers. However, in hepatocellular
      carcinoma (HCC) patients infected with hepatitis B virus (HBV), the relationship
      between let-7a and HBV replication has not been fully elucidated. Liver specimens
      were collected from 23 HCC patients with chronically active HBV. The serum levels
      of the HBV antigens hepatitis B surface antigen (HBsAg) and hepatitis B virus e
      antigen (HBeAg), and the HBV antibodies, anti-HBs, anti-HBe and anti-hepatitis B
      core antigen (anti-HBc) were measured using the microparticle enzyme immunoassay.
      Let-7a levels and HBV DNA copy numbers were measured by quantitative real-time
      PCR (qRT-PCR) and analyzed statistically. A let-7a specific antisense
      oligonucleotide was introduced to the HBV-producing cell line HepG2.2.15 and a
      change in HBV DNA copy numbers was assessed by qRT-PCR. HCC patients with highly
      active HBV replication (>106 DNA copies/mL) showed higher levels of serum HBsAg
      and anti-HBc than patients with less active HBV replication (<103 DNA copies/mL).
      The level of let-7a was lower in malignant tissues than in adjacent normal
      tissues. However, patients with highly active HBV replication demonstrated a
      significantly higher level of let-7a in hepatocarcinoma tissue than patients with
      less active HBV replication ( P < 0.05). A higher level of let-7a was observed in
      the HBV-producing cell line HepG2.2.15 than in HepG2 cells ( P < 0.05), and let
      7a down-regulation by antisense oligonucleotides led to a reduction in HBV DNA
      copy numbers ( P < 0.05), indicating a correlation between the let-7a level and
      HBV replication. Down-regulation of let-7a reduces HBV replication and could
      prevent the development of HCC, suggesting it could be an effective therapeutic
      treatment for HBV infection. Impact statement Although interferon and nucleic
      acid analogues effectively suppress HBV replication in HBV patients, there is no
      treatment which eradicates the virus. Moreover, the therapeutic effect can be
      reduced by virus mutations or drug resistance. Let-7a is a miRNA initially found
      in the nematode as a master regulator of developmental processes, but also exists
      in humans. It has been reported that the transcription of let-7a was much lower
      in HCC than in normal liver tissues and specific miRNA could directly promote
      virus replication. Therefore we hypothesized that transcription of let-7a
      promotes HBV replication, which might compromise the therapeutic effects of
      antivirus treatments. In our present study, we demonstrated a correlation between
      let-7a transcription and HBV replication in surgical specimens obtained from
      patients with HCC, as well as in HCC cell lines. Our finding might be the base
      for a new approach to improve HBV infection treatments in the future.

PMID- 28440733
TI  - Morphological and morphometric analysis of the effects of intralesional tamoxifen
      on keloids.
AB  - The aim of this study was to evaluate the effect of intralesional tamoxifen on
      keloids, particularly on the concentration of fibroblasts, dermal inflammatory
      infiltrate, and collagen degeneration. A prospective study was carried out to
      evaluate keloids in 13 patients of both genders pre- and post-treatment with
      intralesional tamoxifen. Two samples of keloid lesions were obtained by 4-mm
      punch biopsies during the study: the first at the time of diagnostic confirmation
      of keloid and the other eight weeks later at the end of intralesional tamoxifen
      treatment. The biopsy samples were placed in 10% buffered formalin for HE
      staining and morphological and morphometric study. The degree of collagen fiber
      reduction and inflammatory infiltration were analyzed. Student's t-test was used
      for statistical analysis of the mean number of fibroblasts before and following
      tamoxifen treatment ( P < 0.05). The degree of collagen fiber reduction and
      inflammatory infiltration were absent before treatment and present in 100% of
      cases after treatment, while the mean number of fibroblasts was significantly
      lower after intralesional tamoxifen treatment ( P < 0.0001). We conclude that
      intralesional administration of tamoxifen promoted an inflammatory stimulus and
      collagen fiber reduction as well as a significant reduction in the number of
      fibroblasts that produce collagen. Impact statement Effective treatment of keloid
      that is a commonly recurrent dermatosis is very difficult, even after standard
      treatment. Standard treatment consists of partial resection of the lesion
      (shaving excision), in addition to local corticosteroid injection. Therefore,
      there is interest in alternative forms of topical treatment, e.g., selective
      estrogen receptor modulators, particularly tamoxifen has demonstrated in vitro
      studies to be a promising drug. Nevertheless, there is scarcity of publications
      on the effects of intralesional tamoxifen on keloids have been found, leading us
      to the conception of the present study. In this study, tamoxifen has proven to be
      an interesting alternative drug for the topical treatment of keloid, allowing us
      to conclude that the intralesional application of tamoxifen in keloids promotes a
      variable but ever-present inflammatory stimulus, associated with intense
      reduction of collagen fiber, in addition to a significant decrease in the number
      of fibroblasts that produce collagen and are involved in disease maintenance.

PMID- 28440734
TI  - Cholinergic activation suppresses palmitate-induced macrophage activation and
      improves acylation stimulating protein resistance in co-cultured adipocytes.
AB  - Acylation-stimulating protein (ASP), produced through activation of the
      alternative complement immune system, modulates lipid metabolism. Using a trans
      well co-culture cell model, the mitigating role of alpha7-nicotinic acetylcholine
      receptor (alpha7nAChR)-mediated cholinergic pathway on ASP resistance was
      evaluated. ASP signaling in adipocytes via its receptor C5L2 and signaling
      intermediates Galphaq, Gbeta, phosphorylated protein kinase C-alpha, and protein
      kinase C-zeta were markedly suppressed in the presence of TNFalpha or medium from
      palmitate-treated RAW264.7 macrophages, indicating ASP resistance. There was no
      direct effect of alpha7nAChR activation in 3T3-L1 cell culture. However,
      alpha7nAChR activation almost completely reversed the ASP resistance in
      adipocytes co-cultured with palmitate-treated RAW264.7 macrophages. Further,
      alpha7nAChR activation could suppress the production of pro-inflammatory
      molecules TNFalpha and interleukin-6 produced from palmitate-treated co-cultured
      macrophages. These results suggest that macrophages play a significant role in
      the pathogenesis of ASP resistance and alpha7nAChR activation secondarily
      improves adipose ASP resistance through suppression of inflammation in
      macrophages. Impact statement 1. Adipocyte-macrophage interaction in acylation
      stimulating protein (ASP) resistance 2. Lipotoxicity induced inflammatory
      response in ASP resistance 3. A vicious circle between lipotoxicity and
      inflammatory response in ASP resistance 4. Cholinergic modulation of inflammatory
      response in adipocyte and macrophage.

PMID- 28440735
TI  - Nuclear factor E2-related factor 2 knockdown enhances glucose uptake and alters
      glucose metabolism in AML12 hepatocytes.
AB  - Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to
      induce the expression of a variety of antioxidant and detoxification genes.
      Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and
      energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are
      largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA
      transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 +/
      11.1% ( P < 0.05) of that of untransfected control cells. The impacts of Nrf2
      knockdown (NK) on the antioxidant system, inflammatory response, and glucose
      metabolism were then examined in AML12 cells under both high-glucose (33 mmol/L)
      and low-glucose (4.5 mmol/L) conditions. NK lowered the gene and protein
      expression of the anti-oxidases heme oxygenase-1 and NAD(P)H: quinone
      oxidoreductase 1 and increased p-eukaryotic initiation factor-2alphaS51, p
      nuclear factor-kappaB p65S276, and its downstream proinflammatory factors,
      including interleukin-1 beta, tumor necrosis factor-alpha, matrix
      metalloproteinase 2, and matrix metalloproteinase 9, at the protein level. NK
      also altered the protein expression of fibroblast growth factor 21, glucose
      transporter type 4, insulin-like growth factor 1, forkhead box protein O1, p
      AKTS473, and p-GSK3alpha/betaY279/Y216, which are involved in glucose uptake,
      glycogenesis, and gluconeogenesis in AML12 cells. Our results provide a
      comprehensive understanding of the central role of Nrf2 in the regulation of
      glucose metabolism in AML12 hepatocytes, in addition to its classical roles in
      the regulation of redox signaling, endoplasmic reticulum stress and
      proinflammatory responses, and support the potential of Nrf2 as a therapeutic
      target for the prevention and treatment of obesity and other associated metabolic
      syndromes. Impact statement Increasing evidence supports the complexity of Nrf2
      functions beyond the antioxidant and detoxification response. Previous in vivo
      studies employing either Nrf2-knockout or Nrf2-activated mice have achieved a
      similar endpoint: protection against an obese and insulin-resistant phenotype
      that includes impaired lipogenesis and gluconeogenesis in the liver. These
      apparently paradoxical observations led us to evaluate the impact of Nrf2 in
      liver cells in the absence of any influence from the systemic environment,
      including changes in the secretion of adipokines and proinflammatory cytokines by
      adipose tissues. In the present study, Nrf2 knockdown was sufficient to induce
      fundamental changes in the glucose metabolism of AML12 hepatocytes in addition to
      its classical cytoprotective functions. We also discuss similarities and
      differences between our in vitro study and previous in vivo studies, which may be
      helpful to dissect and better understand in vivo data that represents the
      culmination of both local and systemic alterations.

PMID- 28440736
TI  - Levistilide A inhibits angiogenesis in liver fibrosis via vascular endothelial
      growth factor signaling pathway.
AB  - Levistilide A (C24H28O4, molecular weight = 380.48) derived from Angelica
      sinensis (Danggui) has been reported to inhibit hepatic stellate cell
      proliferation. This study investigated the effects of levistilide A on liver
      fibrosis relating to angiogenesis, particularly on the characteristic change in
      liver sinusoidal endothelial cells. LX-2 cells were activated by TGF-beta1, and
      the human hepatic sinusoidal endothelial cells (HHSECs) were induced by
      endothelial cell growth supplement. Cell viability was detected using a
      methylthiazoldiphenyl-tetrazolium bromide assay; F-actin was visualized through
      the fluorescence probe method; cell proliferation was examined using the EdU kit;
      antiangiogenesis activity was assessed using the tube formation assay and
      transgenic zebrafish model. To verify the results in vivo, rats were
      subcutaneously injected with CCl4 twice a week for six weeks to duplicate the
      liver fibrosis model and then treated with 10 mL/kg of normal saline, 4 mg/kg of
      sorafenib, and 3 and 6 mg/kg of levistilide A for three weeks from the fourth
      week. Collagen deposition was detected through Sirius Red staining; liver
      microvasculature was examined through vWF labeling and X-ray 2D imaging;
      sinusoidal fenestrations were observed through scanning electron microscopy;
      collagen I, alpha-SMA, CD31, vascular endothelial growth factor (VEGF), and VEGF
      R2 were detected through Western blotting. Our results indicated that levistilide
      A attenuated LX-2 cell activation and HHSEC proliferation. The ability of HHSECs
      to form tubelike structures in Matrigel was inhibited, and the number of
      functional vessels in transgenic zebrafish decreased. In in vivo experiments,
      levistilide A reduced collagen deposition and the number of new microvessels;
      ameliorated sinusoid capillarization; and downregulated the expression of CD31,
      VEGF, and VEGF-R2. These findings suggest that levistilide A can inhibit liver
      fibrosis through antiangiogenesis by alleviating sinusoid capillarization via the
      VEGF signaling pathway. Impact statement Levistilide A has been reported to
      inhibit hepatic stellate cell (HSC) proliferation. In this study, we further
      investigated the mechanisms of levistilide A on liver fibrosis relating to
      angiogenesis, particularly on the characteristic change in liver sinusoidal
      endothelial cells. The cell models of HSC and liver sinusoidal endothelial cell
      and CCl4 induced liver fibrosis model were used. These results suggest that
      levistilide A can inhibit liver fibrosis through antiangiogenesis by alleviating
      sinusoid capillarization via the vascular endothelial growth factor signaling
      pathway. The effect of levistilide A on liver fibrosis was confirmed, and its
      detailed mechanism was also discussed. These findings suggest that levistilide A
      may be a great potential drug for treating liver fibrosis through
      antiangiogenesis, and this effect will be verified in other fibrotic animal model
      studies or by clinical trials.

PMID- 28440737
TI  - Heart-rate variability depression in porcine peritonitis-induced sepsis without
      organ failure.
AB  - Depression of heart-rate variability (HRV) in conditions of systemic inflammation
      has been shown in both patients and experimental animal models and HRV has been
      suggested as an early indicator of sepsis. The sensitivity of HRV-derived
      parameters to the severity of sepsis, however, remains unclear. In this study we
      modified the clinically relevant porcine model of peritonitis-induced sepsis in
      order to avoid the development of organ failure and to test the sensitivity of
      HRV to such non-severe conditions. In 11 anesthetized, mechanically ventilated
      and instrumented domestic pigs of both sexes, sepsis was induced by fecal
      peritonitis. The dose of feces was adjusted and antibiotic therapy was
      administered to avoid multiorgan failure. Experimental subjects were screened for
      40 h from the induction of sepsis. In all septic animals, sepsis with
      hyperdynamic circulation and increased plasma levels of inflammatory mediators
      developed within 12 h from the induction of peritonitis. The sepsis did not
      progress to multiorgan failure and there was no spontaneous death during the
      experiment despite a modest requirement for vasopressor therapy in most animals
      (9/11). A pronounced reduction of HRV and elevation of heart rate developed
      quickly (within 5 h, time constant of 1.97 +/- 0.80 h for HRV parameter TINN)
      upon the induction of sepsis and were maintained throughout the experiment. The
      frequency domain analysis revealed a decrease in the high-frequency component.
      The reduction of HRV parameters and elevation of heart rate preceded sepsis
      associated hemodynamic changes by several hours (time constant of 11.28 +/- 2.07
      h for systemic vascular resistance decline). A pronounced and fast reduction of
      HRV occurred in the setting of a moderate experimental porcine sepsis without
      organ failure. Inhibition of parasympathetic cardiac signaling probably
      represents the main mechanism of HRV reduction in sepsis. The sensitivity of HRV
      to systemic inflammation may allow early detection of a moderate sepsis without
      organ failure. Impact statement A pronounced and fast reduction of heart-rate
      variability occurred in the setting of a moderate experimental porcine sepsis
      without organ failure. Dominant reduction of heart-rate variability was found in
      the high-frequency band indicating inhibition of parasympathetic cardiac
      signaling as the main mechanism of heart-rate variability reduction. The
      sensitivity of heart-rate variability to systemic inflammation may contribute to
      an early detection of moderate sepsis without organ failure.

PMID- 28440738
TI  - Restricted feeding modulates the daily variations of liver glutamate
      dehydrogenase activity, expression, and histological location.
AB  - Glutamate dehydrogenase is an important enzyme in the hepatic regulation of
      nitrogen and energy metabolism. It catalyzes one of the most relevant anaplerotic
      reactions. Although its relevance in liver homeostasis has been widely described,
      its daily pattern and responsiveness to restricted feeding protocols has not been
      studied. We explored the daily variations of liver glutamate dehydrogenase
      transcription, protein, activity, and histochemical and subcellular location in a
      protocol of daytime food synchronization in rats. Restricted feeding involved
      food access for 2 h each day for three weeks. Control groups included food ad
      libitum as well as acute fasting (21 h fasting) and refeeding (22 h fasting
      followed by 2 h of food access). Glutamate dehydrogenase mRNA, protein, activity,
      and histological location were measured every 3 h by qPCR, Western blot,
      spectrophotometry, and immunohistochemistry, respectively, to generate 24-h
      profiles. Restricted feeding promoted higher levels of mitochondrial glutamate
      dehydrogenase protein and activity, as well as a loss of 24-h rhythmicity, in
      comparison to ad libitum conditions. The rhythmicity of glutamate dehydrogenase
      activity detected in serum was changed. The data demonstrated that daytime
      restricted feeding enhanced glutamate dehydrogenase protein and activity levels
      in liver mitochondria, changed the rhythmicity of its mRNA and serum activity,
      but without effect in its expression in hepatocytes surrounding central and
      portal veins. These results could be related to the adaptation in nitrogen and
      energy metabolism that occurs in the liver during restricted feeding and the
      concomitant expression of the food entrainable oscillator. Impact statement For
      the first time, we are reporting the changes in daily rhythmicity of glutamate
      dehydrogenase (GDH) mRNA, protein and activity that occur in the liver during the
      expression of the food entrained oscillator (FEO). These results are part of the
      metabolic adaptations that modulate the hepatic timing system when the protocol
      of daytime restricted feeding is applied. As highlight, it was demonstrated
      higher GDH protein and activity in the mitochondrial fraction. These results
      contribute to a better understanding of the influence of the FEO in the energy
      and nitrogen handling in the liver. They could also be significant in the
      pathophysiology of hepatic diseases related with circadian abnormalities.

PMID- 28440739
TI  - Featured Article: Pharmacological postconditioning with delta opioid attenuates
      myocardial reperfusion injury in isolated porcine hearts.
AB  - Ischemic preconditioning has been utilized to protect the heart from ischemia
      prior to ischemia onset, whereas postconditioning is employed to minimize the
      consequences of ischemia at the onset of reperfusion. The underlying mechanisms
      and pathways of ischemic pre- and postconditioning continue to be investigated as
      therapeutic targets. We evaluated the administration of a delta opioid agonist or
      cariporide on various parameters associated with myocardial reperfusion injury
      upon reperfusion of isolated porcine hearts. The hearts were reperfused in vitro
      with a Krebs buffer containing either: (1) 1 uM Deltorphin D (delta opioid
      specific agonist, n = 6); (2) 3 uM cariporide (sodium-hydrogen exchange
      inhibitor, n = 4); or (3) no treatment (control, n = 6). Subsequently,
      postischemic hemodynamic performance, arrhythmia burden, relative tissue
      perfusion, and development of necrosis were assessed over a 2 h reperfusion
      period. Postconditioning with Deltorphin D significantly improved diastolic
      relaxation (Tau, P < 0.05 versus controls) and decreased the incidence of
      ventricular arrhythmias during early reperfusion. Additionally, these treated
      hearts demonstrated increased tissue perfusion after 2 h ( P < 0.05 versus
      controls), suggesting improved microvascular function. Delta opioid agonists
      elicited the potential to attenuate reperfusion injury, suggesting a
      postconditioning effect of these agents. We hypothesize that the induced benefits
      of delta opioids, in part, are associated with decreased calcium influx on
      reperfusion, independent of sodium-hydrogen exchange inhibition. Such agents may
      have a potential role in minimizing reperfusion injury associated with coronary
      stenting, bypass surgery, myocardial infarction, cardiac transplantation, or with
      the utilization of heart preservation systems. Impact statement In this study, we
      found that postconditioning with Deltorphin D significantly improved diastolic
      relaxation and decreased the incidence of ventricular arrhythmias during early
      reperfusion. Furthermore, these treated hearts demonstrated increased tissue
      perfusion after 2 h, suggesting improved microvascular function. Delta opioid
      agonists attenuated reperfusion injury, suggestive of a postconditioning effect.
      Such agents may have a potential role in minimizing reperfusion injury associated
      with coronary stenting, bypass surgery, myocardial infarction, cardiac
      transplantation, or with the utilization of heart preservation systems.

PMID- 28440740
TI  - Biomarkers and Bacteria Around Implants and Natural Teeth in the Same
      Individuals.
AB  - BACKGROUND: This cross-sectional study assesses cytokine levels in peri-implant
      crevicular fluid (PICF)/gingival crevicular fluid (GCF) and a selection of
      subgingival/submucosal plaque bacteria from clinically healthy or diseased sites
      in the same individuals. METHODS: Samples from 97 implants/teeth (58 implants [19
      healthy, 20 mucositis, 19 peri-implantitis] and 39 natural teeth [19 healthy, 12
      gingivitis, eight periodontitis] in 15 systemically healthy patients were
      investigated by immunoassay and real-time polymerase chain reaction. Samples were
      obtained first, with probing depth, clinical attachment level, bleeding on
      probing, plaque index scores, and keratinized tissue width then recorded. Data
      were analyzed by Wilcoxon, Mann-Whitney U, and permutation tests on dependent,
      independent, and mixed dependent and independent samples and Spearman
      correlation. RESULTS: Interleukin (IL)-1beta levels were significantly higher in
      PICF samples of healthy implants than in GCF samples of healthy teeth (P =
      0.003), and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL)
      concentrations were significantly higher in the gingivitis than the mucositis
      group (P = 0.004). Biomarker levels were similar in peri-implantitis and
      periodontitis groups (P >0.05). Actinomyces naeslundi and Streptococcus oralis
      levels were significantly higher in the healthy implant group than in healthy
      teeth (P <0.05). Prevotella intermedia and Treponema denticola (Td) levels were
      lower in the mucositis group than the gingivitis group (P <0.05). Prevotella
      oralis and S. oralis levels were significantly higher in the periodontitis group
      (P <0.05), and Td levels were significantly higher in the peri-implantitis group
      (P <0.05). CONCLUSION: There were many similarities but, crucially, some
      differences in biomarker levels (IL-1beta and sRANKL) and bacterial species
      between peri-implant and periodontal sites in the same individuals, suggesting
      similar pathogenic mechanisms.

PMID- 28440741
TI  - Standardized Rat Model Testing Effects of Inflammation and Grafting on Extraction
      Healing.
AB  - BACKGROUND: Loss of alveolar ridge width and height after tooth extraction is
      well documented, but models to evaluate ridge preservation are neither
      standardized nor cost-effective. This rat model characterizes the pattern of bone
      turnover and inflammation after extraction and bone grafting with or without
      local simvastatin (SIM). METHODS: Fifty retired-breeder rats underwent extraction
      of the maxillary right first molar and standard surgical defect creation under
      inhalation/local anesthesia. The left side of each animal served as unmanipulated
      control. Untreated groups (n = 8 to 9 per group) were compared (analysis of
      variance, t test) at days 0, 7, 14, and 28 for alveolar ridge height and width
      and for markers of inflammation and bone turnover by microcomputed tomography,
      histology, and enzyme-linked immunosorbent assay. Seventeen additional specimens
      had defects grafted with either bone mineralized matrix (BMM) or a BMM+SIM
      conjugate. RESULTS: Extraction-induced bone loss (BL) was noted on buccal,
      palatal, and interproximal height (P <0.05) and ridge width (P <0.01). Week 1
      inflammation positively correlated with ridge height; thereafter, a more intense
      inflammatory reaction corresponded to reduction in alveolar bone height and
      density (r = 0.74; P <0.05; Spearman). BMM+SIM preserved the most interproximal
      bone height (P <0.01), increased ridge width and bone density (P <0.01), enhanced
      7-day prostaglandin E2 (P <0.01), and reduced 28-day inflammation density (P
      <0.05). CONCLUSIONS: The standard defect used in the current study paralleled
      human postextraction alveolar BL. Defect grafting, especially BMM+SIM, reduced
      inflammation and preserved bone.

PMID- 28440742
TI  - Leptin Overexpression in Bone Marrow Stromal Cells Promotes Periodontal
      Regeneration in a Rat Model of Osteoporosis.
AB  - BACKGROUND: Osteoporosis is associated with widespread periodontitis and impaired
      periodontal healing. However, there is a lack of information about the outcomes
      of regenerative approaches under the influence of osteoporosis. This study
      investigates the effect of leptin (LEP) overexpression on the regenerative
      potential of bone marrow stromal cells (BMSCs) in an osteoporotic rat periodontal
      fenestration defect model. METHODS: Rat BMSCs were transfected with adenoviruses
      harboring the human (h)LEP gene. Cell proliferation and osteogenic
      differentiation were evaluated. A beta-tricalcium phosphate scaffold seeded with
      transfected cells was implanted into nude mice to investigate ectopic
      osteogenesis and into an osteoporotic rat defect to study periodontal
      regeneration. Regenerated periodontal and bone-like tissues were analyzed by
      histologic methods. RESULTS: hLEP overexpression induced osteogenic
      differentiation of BMSCs as evidenced by the upregulation of osteogenesis-related
      genes such as Runt-related transcription factor 2, alkaline phosphatase (ALP),
      and collagen Type I, as well as increased ALP activity and enhanced
      mineralization. Mice implanted with hLEP-BMSC-containing scaffolds showed more
      extensive formation of bone-like tissue than those in other groups. Periodontal
      defects were also filled to a greater degree when treated with hLEP-BMSCs and
      contained cementum and a well-organized periodontal ligament after 10 and 28
      days. CONCLUSION: hLEP overexpression in BMSCs can stimulate periodontal
      regeneration in osteoporotic conditions and might be a promising strategy for
      periodontal regeneration in patients with osteoporosis.

PMID- 28440743
TI  - Commentary: Targeting Underlying Biologic Mechanisms in Selecting Adjunctive
      Therapies to Improve Periodontal Treatment in Smokers: A Commentary.
AB  - Despite well-established evidence that cigarette smoking is the largest
      modifiable risk factor for periodontal disease and has many deleterious health
      effects, treatment of periodontal disease in smokers remains a challenge of
      periodontal therapy. A recent meta-analysis revealed that adjunctive use of local
      delivery of antimicrobials, but not systemic antibiotic usage, with non-surgical
      periodontal therapy resulted in improvement in clinical periodontal parameters.
      Further evaluation of the current literature reveals that host modulation therapy
      may also result in clinical benefit in smokers. These findings may be tied to the
      underlying pathophysiology of periodontal disease progression in smokers and
      suggest that focused therapies that target known mechanisms of action are
      critical to the success of proposed treatments.

PMID- 28440744
TI  - Factors Associated with Time to Endometriosis Diagnosis in the United States.
AB  - BACKGROUND: We aimed to quantify the time to diagnosis among women with
      endometriosis in the United States (US) and to identify patient- and physician
      related factors affecting diagnostic delay. PATIENTS AND METHODS: An online cross
      sectional survey was conducted from August 6, 2012, through November 14, 2012.
      Respondents aged 18-49 years who reported a physician's diagnosis/suspicion of
      endometriosis within the previous 10 years were included. Endometriosis-related
      symptoms and diagnostic history were captured and summarized. Univariate analyses
      identified factors associated with time from symptom onset to first consultation
      and from first consultation to diagnosis. RESULTS: Of 638 respondents included,
      most (56%) reported seeking care for at least one of the following symptoms:
      menstrual pain (31.6%), nonmenstrual pain (27.3%), and pain during sex (7.5%).
      Most diagnoses (84%) were made by obstetricians/gynecologists; 49% of diagnoses
      were surgical versus 51% nonsurgical. Mean time from symptom onset to diagnosis
      was 4.4 years. Mean time to first consultation was shorter among women aged 40-49
      years versus those aged <18 years (14.2 vs. 43.5 months; p < 0.0001) and those
      consulting for symptoms versus routine/other care (27.9, 24.9, and 28.4 months
      for menstrual pain, nonmenstrual pain, and pain during sex, respectively, vs.
      61.4 months; all p < 0.01). Mean time from first consultation to diagnosis was
      shorter among women aged 40-49 years versus those aged <18 years (12.4 vs. 34.5
      months; p = 0.0009) and those diagnosed by obstetricians/gynecologists versus
      nonobstetricians/gynecologists (21.5 vs. 40.3 months; p = 0.041). CONCLUSIONS:
      Time to endometriosis diagnosis appears to have shortened in the US. Better
      patient and physician education regarding symptomatology may contribute to
      further gains.

PMID- 28440745
TI  - Primaquine in Plasma and Methemoglobinemia in Patients with Malaria Due to
      Plasmodium vivax in the Brazilian Amazon Basin.
AB  - AbstractPrimaquine is the only licensed drug available for the elimination of
      Plasmodium vivax hypnozoites. Methemoglobinemia is currently reported in the
      course of treatment. There is evidence that metabolites of primaquine formed by
      the cytochrome pathway are responsible for methemoglobin formation; a genetic
      polymorphism of cytochrome isoforms; and a potential influence of gender in the
      activities of these enzymes requiring the establishment of dose * response curves
      profiles in different population groups. Concentrations of primaquine in plasma
      and methemoglobin levels were investigated in 54 patients with malaria due to P.
      vivax during the course of the standard regimen of chloroquine with primaquine
      (0.25 mg/kg/day for 14 days). All study subjects lived in an endemic area of the
      Brazilian Amazon Basin. The blood samples were collected before initiation of
      treatment and 3 hours (range 2-4 hours) after the administration of antimalarial
      drugs on days 2, 7, and 14. Plasma primaquine concentrations were similar in both
      genders (males: range = 164-191 ng/mL, females: range = 193-212 ng/mL).
      Methemoglobin levels ranged from 3.3% to 5.9% in males and from 3.1% to 6.5% in
      females. There were no significant correlations between the plasma primaquine
      concentrations or total dose and methemoglobin levels, suggesting that
      unidentified metabolites rather than parent drug were likely responsible for
      changes in methemoglobin levels. There was no significant influence of gender on
      primaquine concentrations in plasma or methemoglobin levels.

PMID- 28440747
TI  - An emergency brake for protein synthesis.
AB  - The integrated stress response is able to rapidly shut down the synthesis of
      proteins in eukaryotic cells.

PMID- 28440746
TI  - Dual interaction of scaffold protein Tim44 of mitochondrial import motor with
      channel-forming translocase subunit Tim23.
AB  - Proteins destined for the mitochondrial matrix are targeted to the inner membrane
      Tim17/23 translocon by their presequences. Inward movement is driven by the
      matrix-localized, Hsp70-based motor. The scaffold Tim44, interacting with the
      matrix face of the translocon, recruits other motor subunits and binds incoming
      presequence. The basis of these interactions and their functional relationships
      remains unclear. Using site-specific in vivo crosslinking and genetic approaches
      in Saccharomyces cerevisiae, we found that both domains of Tim44 interact with
      the major matrix-exposed loop of Tim23, with the C-terminal domain (CTD) binding
      Tim17 as well. Results of in vitro experiments showed that the N-terminal domain
      (NTD) is intrinsically disordered and binds presequence near a region important
      for interaction with Hsp70 and Tim23. Our data suggest a model in which the CTD
      serves primarily to anchor Tim44 to the translocon, whereas the NTD is a dynamic
      arm, interacting with multiple components to drive efficient translocation.

PMID- 28440750
TI  - Where does capillary blood glucose stand following the IMPACT trial? Implications
      of a new way of measuring glucose in routine clinical practice.

PMID- 28440749
TI  - Correction: PCGF6-PRC1 suppresses premature differentiation of mouse embryonic
      stem cells by regulating germ cell-related genes.

PMID- 28440748
TI  - Palmitoylated SCP1 is targeted to the plasma membrane and negatively regulates
      angiogenesis.
AB  - SCP1 as a nuclear transcriptional regulator acts globally to silence neuronal
      genes and to affect the dephosphorylation of RNA Pol ll. However, we report the
      first finding and description of SCP1 as a plasma membrane-localized protein in
      various cancer cells using EGFP- or other epitope-fused SCP1. Membrane-located
      SCP1 dephosphorylates AKT at serine 473, leading to the abolishment of serine 473
      phosphorylation that results in suppressed angiogenesis and a decreased risk of
      tumorigenesis. Consistently, we observed increased AKT phosphorylation and
      angiogenesis followed by enhanced tumorigenesis in Ctdsp1 (which encodes SCP1)
      gene - knockout mice. Importantly, we discovered that the membrane localization
      of SCP1 is crucial for impeding angiogenesis and tumor growth, and this
      localization depends on palmitoylation of a conserved cysteine motif within its
      NH2 terminus. Thus, our study discovers a novel mechanism underlying SCP1
      shuttling between the plasma membrane and nucleus, which constitutes a unique
      pathway in transducing AKT signaling that is closely linked to angiogenesis and
      tumorigenesis.

PMID- 28440751
TI  - Validation in daily clinical situations of Diascope(r), a software developed to
      help healthcare professionals individualize antidiabetic treatment in type 2
      diabetes.
AB  - INTRODUCTION: DiaScope(r) is a software to help in individualized prescription of
      antidiabetic treatment in type 2 diabetes. This study assessed its value and
      acceptability by different professionals. MATERIAL AND METHODS: DiaScope(r) was
      developed based on the ADA-EASD 2012 algorithm and on the recommendation of 12
      international diabetes experts using the RAND/UCLA appropriateness method. The
      current study was performed at a single session. In the first phase, 5 clinical
      scenarios were evaluated, selecting the most appropriated therapeutic option
      among 4 possibilities (initial test). In a second phase, the same clinical cases
      were evaluated with DiaScope(r) (final test).Opinion surveys on DiaScope(r) were
      also performed (questionnaire). RESULTS: DiaScope(r) changed the selected option
      1 or more times in 70.5% of cases. Among 275 evaluated questionnaires, 54.0%
      strongly agree that DiaScope(r) allowed finding easily a similar therapeutic
      scenario to the corresponding patient, and 52.5 among the obtained answers were
      clinically plausible. Up to 58.3% will recommend it to a colleague. In
      particular, primary care physicians with >20 years of professional dedication
      found with DiaScope(r) the most appropriate option for a particular situation
      against specialists or those with less professional dedication (p<.05).
      DISCUSSION: DiaScope(r) is an easy to use tool for antidiabetic drug prescription
      that provides plausible solutions and is especially useful for primary care
      physicians with more years of professional practice.

PMID- 28440752
TI  - Assessment study of the nutritional status, eating habits and physical activity
      of the schooled population of Centelles, Hostalets de Balenya and Sant Marti de
      Centelles (ALIN 2014 Study).
AB  - BACKGROUND AND OBJECTIVE: Malnourishment can be caused by either a lack of food
      or an excess of low-nutrient foods. Due to several factors, this predisposes
      children to academic failure. The objective of this study is to estimate the
      prevalence of school children with eating problems, study their nutrition level,
      food quality in the diet, and level of physical activity. MATERIAL AND METHODS:
      The study involved the school children between 3 months and 16.5 years of age in
      the municipalities of Centelles, Hostalets de Balenya and Sant Marti de
      Centelles. Personal, age, nutrition and physical activity data were collected for
      the descriptive and bivariate analyses. RESULTS: A total of 1,374 children were
      included, of which 122 were under 3 years of age (8.9%). Obesity was recorded in
      2.5%, while 17.2, 15.6 and 64.8% were overweight, underweight and of normal
      weight, respectively. The remaining 1,252 children were over 3 years of age
      (91.1%), and obesity was recorded in 8.1%, while 26.1, 11.0 and 62.9% were
      overweight, underweight and of normal weight, respectively. Adherence to the
      Mediterranean diet decreased significantly with increasing age. The maintenance
      of body weight was significantly correlated to the consumption of carbohydrates
      for breakfast before going to school, daily fruit consumption, and not having a
      need for care from the social services. The differences in physical activity and
      a sedentary lifestyle proved significant between males and females. CONCLUSION:
      Being underweight and overweight are factors related to eating habits and
      dependency upon the social services.

PMID- 28440753
TI  - Is HLA the cause of the high incidence of type 1 diabetes in the Canary Islands?
      Results from the Type 1 Diabetes Genetics Consortium (T1DGC).
AB  - INTRODUCTION: Incidence of childhood-onset type 1 diabetes mellitus in the Canary
      Islands is the highest reported so far in Spain, and among the highest worldwide.
      The HLA region accounts for approximately half the genetic risk of type 1
      diabetes. Our aim was to assess distribution of high-risk and protective HLA
      haplotypes in the Canarian families included in the T1DGC, as compared to the
      rest of Spain. METHODS: The T1DGC study, an international project to study the
      genetics and pathogenesis of type 1 diabetes, enrolled more than 3000 families
      with type 1 diabetes worldwide. Spain provided 149 of these families, of whom 42
      were from Tenerife and Gran Canaria. HLA was genotyped centrally using a PCR
      based, sequence-specific oligonucleotide probe system. Haplotypes were
      reconstructed using the deterministic algorithm alleHap in the R programming
      environment. Based on prior T1DGC results in Caucasian population, haplotypes
      DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB1*0302, DRB1*0301-DQA1*0501
      DQB1*0201, DRB1*0402-DQA1*0301-DQB1*0302 and DRB1*0404-DQA1*0301-DQB1*0302 were
      considered high-risk. DRB1*0701-DQA1*0201-DQB1*0303, DRB1*1401-DQA1*0101
      DQB1*0503, DRB1*1501-DQA1*0102-DQB1*0602, DRB1*1101-DQA1*0501-DQB1*0301,
      DRB1*1104-DQA1*0501-DQB1*0301, DRB1*1303-DQA1*0501-DQB1*0301, DRB1*1301-DQA1*0103
      DQB1*0603 and DRB1*0403-DQA1*0301-DQB1*0302 were considered protective. The
      distribution of protective, high-risk, and other haplotypes in the (first two)
      affected siblings and unaffected parents from Canarian and non-Canarian Spanish
      families was compared (Chi-square test). RESULTS: No significant differences were
      found between the regions in distribution of the HLA haplotypes in the affected
      siblings or in the non-affected parents. CONCLUSIONS: The high incidence of
      childhood-onset type 1 diabetes in the Canarian population does not appear to be
      explained by a greater prevalence of high-risk class II HLA haplotypes in
      families with the disease. However, sample size limits the differences that can
      be detected in this study.

PMID- 28440754
TI  - Novel aspects in histopathology of the pituitary gland.
AB  - The sellar and parasellar region is a complex anatomical area in which several
      diseases may develop. The pituitary gland may be affected by a wide range of
      conditions having similar clinical characteristics. Diagnosis of these lesions
      requires a multidisciplinary approach including, in addition to clinical,
      laboratory, imaging, and surgical findings, histological diagnosis of pituitary
      adenomas to guide therapeutic management. As the result of development in recent
      years of new immunohistochemical techniques, histopathological classification has
      become more complex and wide, and not only continues to be the gold standard in
      diagnosis, but also has prognostic implications. The aim of this review is to
      provide a clear and simple update of the main concepts of histological diagnosis
      of the most common pituitary conditions, especially for professionals in direct
      contact with such diseases.

PMID- 28440755
TI  - Dysfunctional immunometabolic effects of vitamin D deficiency, increased
      cardiometabolic risk. Potential epidemiological alert in America?
AB  - Vitamin D deficiency is a serious public health problem worldwide that affects
      not only skeletal health, but also a wide range of acute and chronic diseases.
      However, there is still skepticism because of the lack of randomized, controlled
      trials to support association studies on the benefits of vitamin D for non
      skeletal health. This review was based on articles published during the 1980-2015
      obtained from the Cochrane Central Register of controlled trials, MEDLINE and
      PubMed, and focuses on recent challenges with regard to the definition of vitamin
      D deficiency and how to achieve optimal serum 25-hydroxyvitamin D levels from
      dietary sources, supplements, and sun exposure. The effect of vitamin D on
      epigenetic fetal programming and regulation of genes that may potentially explain
      why vitamin D could have such lifelong comprehensive health benefits is reviewed.
      Optimization of vitamin D levels in children and adults around the world has
      potential benefits to improve skeletal health and to reduce the risk of chronic
      diseases, including some types of cancer, autoimmune diseases, infectious
      diseases, type 2 diabetes mellitus, and severe cardiovascular disorders such as
      atherothrombosis, neurocognitive disorders, and mortality.

PMID- 28440756
TI  - Type 2 diabetes, risk of sleep apnea-hypopnea syndrome, and quality of life
      associated to sleep breathing disorders.

PMID- 28440757
TI  - Sellar collision tumor involving a primary fibrosarcoma: Clinical, morphological
      and immunohistochemical study of a case and review of the literature.

PMID- 28440758
TI  - Abdominal pain and hipertensive crisis as initial manifestation of a malignant
      pheocromocytoma.

PMID- 28440760
TI  - Hypothalamic obesity after craniopharyngioma surgery: Treatment with a long
      acting glucagon like peptide 1 derivated.

PMID- 28440759
TI  - Utility of elastography in thyroid nodules with indeterminate cytology.

PMID- 28440761
TI  - Recommendations on the effect of antidiabetic drugs in bone.
AB  - OBJECTIVE: To provide recommendations on the effect of antidiabetic drugs on bone
      fragility to help select the most adequate antidiabetic treatment, especially in
      diabetic patients with high risk of fracture. PARTICIPANTS: Members of the Bone
      Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: The
      GRADE system (Grading of Recommendations, Assessment, Development, and
      Evaluation) was used to establish both the strength of recommendations and the
      quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the
      following terms associated to the name of each antidiabetic drug: AND
      "osteoporosis", "fractures", "bone mineral density", "bone markers",
      "calciotropic hormones". Papers in English with publication date before 30 April
      2016 were reviewed. Recommendations were jointly discussed by the Working Group.
      CONCLUSIONS: The document summaries the data on the potential effects of
      antidiabetic drugs on bone metabolism and fracture risk.

PMID- 28440762
TI  - Consensus statement for use and technical requirements of thyroid ultrasound in
      endocrinology units.
AB  - Thyroid nodule detection has increased with widespread use of ultrasound, which
      is currently the main tool for detection, monitoring, diagnosis and, in some
      instances, treatment of thyroid nodules. Knowledge of ultrasound and adequate
      instruction on its use require a position statement by the scientific societies
      concerned. The working groups on thyroid cancer and ultrasound techniques of the
      Spanish Society of Endocrinology and Nutrition have promoted this document, based
      on a thorough analysis of the current literature, the results of multicenter
      studies and expert consensus, in order to set the requirements for the best use
      of ultrasound in clinical practice. The objectives include the adequate framework
      for use of thyroid ultrasound, the technical and legal requirements, the clinical
      situations in which it is recommended, the levels of knowledge and learning
      processes, the associated responsibility, and the establishment of a standardized
      reporting of results and integration into hospital information systems and
      endocrinology units.

PMID- 28440763
TI  - Recommended vitamin D levels in the general population.
AB  - OBJECTIVE: To provide recommendations based on evidence on the management of
      vitaminD deficiency in the general population. PARTICIPANTS: Members of the Bone
      Metabolism Working Group of the Spanish Society of Endocrinology. METHODS:
      Recommendations were formulated using the GRADE system (Grading of
      Recommendations, Assessment, Development, and Evaluation) to describe both the
      strength of recommendations and the quality of evidence. A systematic search was
      made in MEDLINE (Pubmed) using the term VitaminD and the name of each issue.
      Papers in English and Spanish with publication date before 17 March 2016 were
      included. Recommendations were jointly discussed by the Working Group.
      CONCLUSIONS: This document summarizes the data about vitaminD deficiency in terms
      of prevalence, etiology, screening indications, adequate levels and effects of
      supplementation on bone and non-skeletal health outcomes.

PMID- 28440764
TI  - Endocrinologist and oncologist, a friendship under construction about obesity.

PMID- 28440765
TI  - Association of metabolic syndrome with low birth weight, intake of high-calorie
      diets and acanthosis nigricans in children and adolescents with overweight and
      obesity.
AB  - OBJECTIVE: The theory of fetal programming suggests that low birth weight (LBW)
      predisposes to greater food intake and increases the chance of overweight and
      obesity, which are in turn associated to conditions such as metabolic syndrome
      (MS) and acanthosis nigricans. The study objective was to ascertain whether an
      association exists between MS, LBW, intake of high-calorie diets, and acanthosis
      nigricans in children and adolescents with overweight or obesity. MATERIAL AND
      METHODS: A case-control was conducted on 100 children who attended the overweight
      and obesity outpatient clinic of the OPD Hospital Civil de Guadalajara "Fray
      Antonio Alcalde". Subjects were stratified in groups with and without MS based on
      the criteria of the International Diabetes Federation for children aged less than
      16 years. Data on LBW, intake of high-calorie diets for 24-hour dietary recalls
      (average 2 days a week), and acanthosis nigricans (Simone criteria) were obtained
      by questioning the parents. Frequencies and logistic regression were calculated
      using SPSS version 22. RESULTS: The results show that 82% of children and
      adolescents were obese and 18% overweight, and 73% had MS. MS was associated to
      LBW (OR: 4.83 [95% CI: 1.9-12.47]), high-calorie diets (OR:136.8 [95% CI: 7.7
      2434]), and acanthosis nigricans (OR: 1872 [95% CI: 112.9-31028]). CONCLUSIONS:
      In children and adolescents with overweight and obesity, LBW, high-calorie diets,
      and acanthosis nigricans are associated to a higher probability of MS.

PMID- 28440766
TI  - Unfavorable cytokine and adhesion molecule profiles during and after pregnancy,
      in women with gestational diabetes mellitus.
AB  - BACKGROUND: Gestational diabetes mellitus is a significant risk factor for
      metabolic syndrome and cardiovascular disease. AIMS: To assess the relationships
      between components of the metabolic syndrome and cytokine and adhesion molecule
      levels in women with GDM during pregnancy and after delivery. PATIENTS AND
      METHODS: A prospective case-control study on a sample of 126 pregnant women (63
      with and 63 without gestational diabetes mellitus). In an intra-subject analysis,
      41 women with history of gestational diabetes mellitus and 21 controls were re
      assessed in the postpartum period. Clinical data and levels of cytokines and
      adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months
      after delivery. RESULTS: In the postpartum period, there were significantly
      higher levels of tumor necrosis factor alpha in both cases and controls, and of
      adiponectin in controls. Cases showed higher leptin levels, with no significant
      differences during and after pregnancy. No significant differences were seen in
      adhesion molecules and interleukin-6 between cases and controls during pregnancy
      and in the postpartum period, but levels of both were higher in cases. During
      pregnancy and after delivery, adiponectin decreased in cases and increased in
      controls. Significant positive correlations were seen between adiponectin and
      fasting blood glucose levels and vascular cell adhesion molecule-1, and also
      between leptin and tumor necrosis factor alpha levels. CONCLUSIONS: The results
      suggest that increased inflammation and transient hyperglycemia during pregnancy
      would represent a latent form of metabolic syndrome, with an increased risk for
      type 2 diabetes mellitus and future cardiovascular disease.

PMID- 28440767
TI  - Zinc alpha-2 glycoprotein is overproduced in Cushing's syndrome.
AB  - INTRODUCTION: Cushing syndrome (CS), an endogenous hypercortisolemic condition
      with increased cardiometabolic morbidity, leads to development of abdominal
      obesity, insulin resistance, diabetes and proatherogenic dyslipidemia. Zinc alpha
      2 glycoprotein (ZAG) is a recently characterized lipolytic adipokine implicated
      in regulation of adipose tissue metabolism and fat distribution. In vitro and
      animal studies suggest that glucocorticoids interact with ZAG secretion and
      action. To assess the relationship between ZAG and glucocorticoids in a human
      model of hypercortisolism, circulating ZAG levels were tested in patients with CS
      and its counterpart controls. METHODS: An observational, cross-sectional study on
      39 women, 13 with active CS and 26 controls matched by age and body mass index.
      Plasma ZAG levels (MUg/ml) were measured by ELISA and correlated with
      hypercortisolism, metabolic, and phenotypic parameters. RESULTS: Plasma ZAG
      levels were significantly higher in patients with CS compared to controls (64.3+/
      16.6 vs. 44.0+/-16.1, p=0.002). In a univariate analysis, ZAG levels positively
      correlated to 24-h urinary free cortisol (p=0.001), body mass index (p=0.02), non
      esterified fatty acids (p=0.05), glucose (p=0.003), LDL-C (p=0.028), and type 2
      diabetes mellitus (p=0.016), and were inversely related to total adiponectin
      levels (p=0.035). In a multivariate analysis, after adjusting for CS, ZAG levels
      only correlated with body mass index (p=0.012), type 2 diabetes mellitus
      (p=0.004), and glucose (p<0.001). CONCLUSION: This study provides initial
      evidence that plasma ZAG levels are higher in patients with CS as compared to
      controls. The close relationship of ZAG with metabolic and phenotypic changes in
      CS suggests that ZAG may play a significant role in adipose tissue changes in
      hypercortisolism.

PMID- 28440768
TI  - Clinical and metabolic profile of patients with latent autoimmune diabetes in
      adults in specialized care in Madrid.
AB  - OBJECTIVE: To report the clinical characteristics of patients with latent
      autoimmune diabetes in adults (LADA), and to ascertain their metabolic control
      and associated chronic complications. METHODS: Patients with DM attending
      specialized medical care in Madrid who met the following criteria: age at
      diagnosis of DM >30years, initial insulin independence for at least 6months and
      positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis,
      associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic
      control, and presence of chronic complications were analyzed. RESULTS: Number of
      patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis:
      49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time:
      12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%.
      Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral
      antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma
      glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity,
      8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL.
      Triglycerides: 89mg/dL. Known chronic complications: 28%. CONCLUSIONS:
      Recognition of LADA may be delayed by several years. There is a heterogeneous
      pancreatic insulin reserve which is negative related to glycemic parameters. Most
      patients are poorly controlled despite intensive insulin therapy. They often have
      overweight, but have adequate control of BP and lipid profile and a low incidence
      of macrovascular complications.

PMID- 28440769
TI  - Advanced glycation end-products in morbid obesity and after bariatric surgery:
      When glycemic memory starts to fail.
AB  - BACKGROUND AND OBJECTIVE: Advanced glycation end-products (AGEs) are a marker of
      metabolic memory. Their levels increases when oxidative stress, inflammation, or
      chronic hyperglycemia exists. The role of morbid obesity in AGE levels, and the
      impact of bariatric surgery on them are unknown. PATIENTS AND METHOD: An
      observational study with three sex- and age-matched cohorts: 52 patients with
      obesity, 46 patients undergoing bariatric surgery in the last 5 years, and 46
      control subjects. AGE were measured using skin autofluorescence (SAF) in the
      forearm with an AGE ReaderTM (DiagnOptics Technologies, Groningen, The
      Netherlands). Presence of metabolic syndrome was assessed. RESULTS: Patients with
      morbid obesity had higher SAF levels (2.14+/-0.65AU) than non-obese subjects
      (1.81+/-0.22AU; P<.001), which was mainly attributed to obese subjects with
      metabolic syndrome (2.44+/-0.67 vs. 1.86+/-0.51AU; P<.001). After bariatric
      surgery, SAF continued to be high (2.18+/-0.40AU), and greater as compared to the
      non-obese population (P<.001). A multivariate analysis showed that age and
      presence of metabolic syndrome (but not sex or body mass index) were
      independently associated to SAF (R2=0.320). CONCLUSION: SAF is increased in
      patients with morbid obesity and metabolic syndrome, mainly because of the
      existence of type 2 diabetes mellitus. In the first 5 years following bariatric
      surgery, weight loss and metabolic improvement are not associated with a parallel
      decrease in subcutaneous AGE levels.

PMID- 28440770
TI  - Epigenetic modulators of thyroid cancer.
AB  - There are some well known factors involved in the etiology of thyroid cancer,
      including iodine deficiency, radiation exposure at early ages, or some genetic
      changes. However, epigenetic modulators that may contribute to development of
      these tumors and be helpful to for both their diagnosis and treatment have
      recently been discovered. The currently known changes in DNA methylation, histone
      modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed
      here.

PMID- 28440771
TI  - Interference of Hb D-Los Angeles on the measurement of glycated hemoglobin. A
      case report.

PMID- 28440772
TI  - Cataract: A forgotten early complication of diabetes in children and adolescents.

PMID- 28440773
TI  - Impact of calcimimetics in surgery of secondary hyperparathyroidism.

PMID- 28440774
TI  - Diagnostic and therapeutic update on diabetic foot osteomyelitis.
AB  - Diabetic foot osteomyelitis (DFO) is the most common infection associated to
      diabetic foot ulcers (DFU). This review is designed to provide an update on the
      diagnosis and treatment of DFO based on an analysis of MEDLINE through PubMed
      using as search criterion "Diabetic Foot Osteomyelitis". Authors have included in
      this review the most relevant manuscripts regarding diagnosis and treatment of
      DFO. After review and critical analysis of publications, it may be concluded that
      diagnosis of DFO is not simple because of its heterogeneous presentation.
      Clinical inflammatory signs, probe-to-bone test, and plain X-rays are postulated
      as the basic tests for clinical diagnosis when DFO is suspected. Diagnosis should
      be supported by laboratory tests, of which ESR (>70mm/h) has been shown to be
      most precise. MRI is the most accurate imaging test, especially for differential
      diagnosis with Charcot foot. Pathogen isolation by bone culture is essential when
      the patient is treated with ATB only. Medical or surgical treatment should be
      based on the clinical characteristics of the patient and the lesion. Surgery
      should always be an option if medical treatment fails.

PMID- 28440775
TI  - Epidemiological bases and molecular mechanisms linking obesity, diabetes, and
      cancer.
AB  - The association between diabetes and cancer was hypothesized almost one century
      ago. Today, a vast number of epidemiological studies support that obese and
      diabetic populations are more likely to experience tissue-specific cancers, but
      the underlying molecular mechanisms remain unknown. Obesity, diabetes, and cancer
      share many hormonal, immune, and metabolic changes that may account for the
      relationship between diabetes and cancer. In addition, antidiabetic treatments
      may have an impact on the occurrence and course of some cancers. Moreover, some
      anticancer treatments may induce diabetes. These observations aroused a great
      controversy because of the ethical implications and the associated commercial
      interests. We report an epidemiological update from a mechanistic perspective
      that suggests the existence of many common and differential individual mechanisms
      linking obesity and type 1 and 2 diabetes mellitus to certain cancers. The
      challenge today is to identify the molecular links responsible for this
      association. Classification of cancers by their molecular signatures may
      facilitate future mechanistic and epidemiological studies.

PMID- 28440776
TI  - Mosaicism XXY/X0.

PMID- 28440777
TI  - Restricted diet in fruits causes scurvy in a child of 7 years old.

PMID- 28440778
TI  - Metastatic malignant struma ovarii: Two scenarios of the same pathology.

PMID- 28440779
TI  - The PREDIMED study.

PMID- 28440780
TI  - Frequency and management of diabetes and hyperglycemia at emergency departments:
      the GLUCE-URG Study.
AB  - INTRODUCTION: Hyperglycemia is a common finding at hospital emergency rooms in
      diabetic patients, but few data are available on its frequency, management, and
      subsequent impact based on the assessment made at Emergency rooms. OBJECTIVES: To
      ascertain the frequency of diabetes mellitus and hyperglycemia in patients
      admitted from Emergency rooms. Second, to describe management of hyperglycemia at
      Emergency rooms, and to analyze its potential impact on the course and management
      of patients during admission. PATIENTS AND METHODS: All patients admitted from
      the Emergency room for three consecutive weeks were enrolled. Hyperglycemia was
      defined as two blood glucose measurements >= 180mg/dl in the first 48hours after
      admission. RESULTS: 36.6% of patients admitted from the Emergency room were
      diabetic, and 58% of these had early, sustained hyperglycemia. On the other hand,
      27% of patients admitted from the Emergency room had hyperglycemia (78.3% of
      diabetic patients and 21.7% with no known diabetes). Diabetic patients with
      hyperglycemia had higher blood glucose levels than non-diabetic patients (p<.01).
      Average hospital stay was 8+/-6.4 days, with no differences between the groups.
      Hyperglycemia is rarely reported as a diagnosis in the emergency rooms discharge
      report. In standard hospitalization, this diagnosis appears more commonly in
      patients with known diabetes (OR 2.5 p<.001). CONCLUSIONS: Prevalence of diabetic
      patients admitted from emergency rooms is very high. In addition, although
      hyperglycemia is very common in patients admitted from emergency rooms, there is
      a trend to underestimate its significance. Based on our results, we think that
      implementation of measures to give greater visibility to diagnosis of
      hyperglycemia could help improve application of established protocols.

PMID- 28440781
TI  - Immunohistochemical detection of the BRAF V600E mutation in papillary thyroid
      carcinoma. Evaluation against real-time polymerase chain reaction.
AB  - INTRODUCTION: The BRAF V600E mutation is the most common genetic change in
      papillary thyroid carcinoma and is associated with a poorer clinical course.
      Usual methods for its study (DNA sequencing or molecular test based on PCR) are
      expensive and time-consuming. Recently, immunohistochemistry (IHC) for BRAF
      mutation has been introduced. OBJECTIVE: To compare the results of IHC and real
      time PCR (RT-PCR) in the detection of BRAF V600E mutation in papillary thyroid
      carcinoma. Analysis of clinical and pathological differences depending on RT-PCR
      results is included. METHODS: A prospective study was performed in 82 consecutive
      samples, 54 of them taken through a core needle biopsy. IHC was performed on
      tissue fixed for 24hours with 10% neutral formalin using the anti-BRAF V600E (VE
      1) mouse monoclonal primary antibody and was rated as positive or negative. DNA
      was extracted from formalin-fixed, paraffin-embedded tissues by manual
      microdissection, and BRAF mutation was detected by RT-PCR using the Cobas(r) 4800
      BRAF V600 mutation test (Roche). RESULTS: Both techniques were concordant in 81
      cases, and BRAF was positive in 49. Discordance appeared in a follicular variant
      showing positive IHC and negative RT-PCR, attributed to histological
      heterogeneity. Cost of materials for IHC was less than half of the cost for RT
      PCR. CONCLUSIONS: IHC appears to be a reliable, economical and easily available
      alternative to molecular biology techniques for routine detection of the BRAF
      V600E mutation in papillary thyroid carcinoma patients, provided optimal fixation
      conditions are used. It may be a useful technique in hospitals with no access to
      molecular biology techniques.

PMID- 28440782
TI  - Systematization of clinical trials related to treatment of metabolic syndrome,
      1980-2015.
AB  - INTRODUCTION: Despite the clinical, epidemiological, and economic significance of
      metabolic syndrome, the profile of clinical trials on this disease is unknown.
      OBJECTIVE: To characterize the clinical trials related to treatment of metabolic
      syndrome during the 1980-2015 period. METHODS: Systematic review of the
      literature using an ex ante search protocol which followed the phases of the
      guide Preferred Reporting Items for Systematic Reviews and Meta-Analyses in four
      multidisciplinary databases with seven search strategies. Reproducibility and
      methodological quality of the studies were assessed. RESULTS: One hundred and six
      trials were included, most from the United States, Italy, and Spain, of which
      63.2% evaluated interventions effective for several components of the syndrome
      such as diet (40.6%) or physical activity (22.6%). Other studies assessed drugs
      for a single factor such as hypertension (7.5%), hypertriglyceridemia (11.3%), or
      hyperglycemia (9.4%). Placebo was used as control in 54.7% of trials, and outcome
      measures included triglycerides (52.8%), HDL (48.1%), glucose (29.2%), BMI
      (33.0%), blood pressure (27.4%), waist circumference (26.4%), glycated hemoglobin
      (11.3%), and hip circumference (7.5%). CONCLUSION: It was shown that studies ob
      efficacy of treatment for metabolic syndrome are scarce and have mainly been
      conducted in the last five years and in high-income countries. Trials on
      interventions that affect three or more factors and assess several outcome
      measures are few, and lifestyle interventions (diet and physical activity) are
      highlighted as most important to impact on this multifactorial syndrome.

PMID- 28440783
TI  - Social vulnerability and hypoglycemia among patients with diabetes.
AB  - Lower-income populations are hit harder by the diabetes epidemic as regards both
      prevalence and the risk of complications. Food Insecurity is one of the
      mechanisms through which poverty may predispose people with low socio-economic
      status to poorer control and higher complication rates. The United Nations Food
      and Agriculture Organization defined food security as "the right to have access
      to sufficient nutritional and culturally acceptable food choices." Adults
      suffering from diabetes with limited income have a 40% greater chance of having
      food insecurity and an inadequate blood glucose control. Such patients have a two
      fold greater risk of developing severe hypoglycemia. In addition, several studies
      have shown that social vulnerability resulting from food insecurity, low
      socioeconomic status, low educational levels, and poor health education is an
      independent risk factor for hypoglycemia, even after conventional predictors are
      controlled. This review analyzes the literature available on social vulnerability
      as a non-conventional risk factor for development of hypoglycemia in diabetic
      subjects.

PMID- 28440785
TI  - Impacts of HBV rtH55R polymerase substitution on viral replication and rtM204I/V
      resistance to nucleoside/nucleotide antiviral drugs.
AB  - BACKGROUND: High genetic variability at the reverse transcriptase (RT) region of
      HBV could confer resistance to nucleoside/nucleotide analogues (NUCs). The aim of
      this study was to identify new RT amino acid (AA) substitutions related to NUC
      resistance. METHODS: HBV RT sequences of genotype C from 501 chronic hepatitis B
      (CHB) patients were analysed to identify potential RT substitutions related to
      NUC resistance. In vitro studies without and with NUCs were performed in a HepG2
      cell line transfected by clones with RT harbouring wild-type or substituted AA(s)
      of interest. RESULTS: Among 261 NUC-treated CHB patients, we found a high
      detection rate of rtM204I/V substitution (30.7% [80/261]). We identified a new
      substitution of rtH55R, and its detection rate had a significantly increasing
      trend from 3.8% (9/240) in the untreated group to 7.2% (13/181) or 33.8% (27/80)
      in the treated group with rtM204 or with rtM204I/V substitutions (P<0.0001). In
      vitro studies showed that rtH55R had a similar HBV DNA level compared to wild
      type. The rtH55R+rtM204I clone had a significantly better replication capacity
      than the rtM204I clone without NUCs (P<0.05). The replication capacity of the
      rtM204I clone was found to significantly decrease under lamivudine treatment, but
      this was not found in the rtH55R+rtM204I clone. CONCLUSIONS: We identified a new
      HBV RT substitution of rtH55R in genotype-C-infected CHB patients. It is
      frequently found in combination with rtM204I/V substitution under NUC treatment.
      In vitro studies suggest that it might play some replication compensatory role in
      rtM204I mutants under lamivudine treatment.

PMID- 28440784
TI  - Dual-energy CT characteristics of colon and rectal cancer allows differentiation
      from stool by dual-source CT.
AB  - PURPOSE: We aimed to determine dual-energy computed tomography (DECT)
      characteristics of colorectal cancer and investigate effectiveness of DECT method
      in differentiating tumor from stool in patients with colorectal cancer. METHODS:
      Fifty consecutive patients with colorectal tumors were enrolled. Staging was
      performed by DECT (80-140 kV) using dual-source CT after rectal air insufflation
      and without bowel preparation. Both visual and quantitative analyses were
      performed at 80 kV and 140 kV, on iodine map and virtual noncontrast (VNC)
      images. RESULTS: All colorectal tumors had homogeneous pattern on iodine map.
      Stools demonstrated heterogeneous pattern in 86% (43/50) and homogeneous pattern
      in 14% (7/50) on iodine maps and were less visible on VNC images. Median density
      of tumors was 54 HU (18-100 HU) on iodine map and 28 HU (11-56 HU) on VNC images.
      Median density of stool was 36.5 HU (8-165 HU) on iodine map and -135.5 HU (-438
      HU to -13 HU) on VNC images. The density of stools was significantly lower than
      tumors on both iodine map and VNC images (P < 0.001). The cutoff point of density
      measurement on VNC images was -1 HU with area under the curve of 1 and a
      sensitivity and specificity of 100%. CONCLUSION: Density or visual analysis of
      iodine map and VNC DECT images allow accurate differentiation of tumor from
      stool.

PMID- 28440786
TI  - Magnetic and transport properties of a layered compound Ce2Te5.
AB  - Ce2Te5 single crystals were successfully grown using RbCl/LiCl flux method. The
      structure of Ce2Te5 can be viewed as a combination of CeTe2 and CeTe3. The
      experimental results of magnetic susceptibility [Formula: see text], isothermal
      magnetization M(H), electrical resistivity [Formula: see text], and heat capacity
      C(T) show two clear anomalies at 5.1 and 2.3 K, which correspond to a
      ferrimagnetic and a possible antiferromagnetic transition, respectively. Both of
      [Formula: see text] and C(T) confirm a third transition at 0.9 K. The resistivity
      shows a huge anisotropy with the current applied in [Formula: see text] and
      [Formula: see text] directions. Our experimental results prefer the scenario that
      the three consecutive transitions in Ce2Te5 are attributed to two different kinds
      of origin, which are independent and responsible for the magnetic orders observed
      in CeTe2 and CeTe3.

PMID- 28440787
TI  - Phase behaviour of 2D MnWO x and FeWO x ternary oxide layers on Pd(1 0 0).
AB  - The structure and properties of ternary oxide materials at the nanoscale are
      poorly explored both on experimental and theoretical levels. With this work we
      demonstrate the successful on-surface synthesis of two-dimensional (2D) ternary
      oxide, MnWO x and FeWO x , nanolayers on a Pd(1 0 0) surface and the
      understanding of their new structure and phase behaviour with the help of state
      of-art surface structure and spectroscopy techniques. We find that the 2D MnWO x
      and FeWO x phases, prepared under identical thermodynamic conditions, exhibit
      similar structural properties, reflecting the similarity of the bulk MnWO4 and
      FeWO4 phases with the wolframite structure. Structure models of prototypical 2D
      ternary oxide phases are proposed and discussed in the light of new structure
      architecture concepts which have no analogues in the bulk.

PMID- 28440788
TI  - Multi-layered hierarchical nanostructures for transparent monolithic dye
      sensitized solar cell architectures.
AB  - Monolithic dye-sensitized solar cell (DSC) architectures hold great potential for
      building-integrated photovoltaics applications. They indeed benefit from lower
      weight and manufacturing costs as they avoid the use of a transparent conductive
      oxide (TCO)-coated glass counter electrode. In this work, a transparent
      monolithic DSC comprising a hierarchical 1D nanostructure stack is fabricated by
      physical vapor deposition techniques. The proof of concept device comprises
      hyperbranched TiO2 nanostructures, sensitized by the prototypical N719, as
      photoanode, a hierarchical nanoporous Al2O3 spacer, and a microporous indium tin
      oxide (ITO) top electrode. An overall 3.12% power conversion efficiency with 60%
      transmittance outside the dye absorption spectral window is demonstrated. The
      introduction of a porous TCO layer allows an efficient trade-off between
      transparency and power conversion. The porous ITO exhibits submicrometer voids
      and supports annealing temperatures above 400  degrees C without compromising its
      optoelectronical properties. After thermal annealing at 500  degrees C, the
      resistivity, mobility, and carrier concentration of the 800 nm-thick porous ITO
      layer are found to be respectively 2.3 * 10-3 Omega cm-1, 11 cm2 V-1 s-1, and
      1.62 * 1020 cm-3, resulting in a series resistance in the complete device
      architecture of 45 Omega. Electrochemical impedance and intensity-modulated
      photocurrent/photovoltage spectroscopy give insight into the electronic charge
      dynamic within the hierarchical monolithic DSCs, paving the way for potential
      device architecture improvements.

PMID- 28440789
TI  - Corrigendum: One Step Quantum Key Distribution Based on EPR Entanglement.

PMID- 28440790
TI  - Large-scale modeled contemporary and future water temperature estimates for 10774
      Midwestern U.S. Lakes.
AB  - Climate change has already influenced lake temperatures globally, but
      understanding future change is challenging. The response of lakes to changing
      climate drivers is complex due to the nature of lake-atmosphere coupling, ice
      cover, and stratification. To better understand the diversity of lake responses
      to climate change and give managers insight on individual lakes, we modelled
      daily water temperature profiles for 10,774 lakes in Michigan, Minnesota, and
      Wisconsin for contemporary (1979-2015) and future (2020-2040 and 2080-2100) time
      periods with climate models based on the Representative Concentration Pathway
      8.5, the worst-case emission scenario. In addition to lake-specific daily
      simulated temperatures, we derived commonly used, ecologically relevant annual
      metrics of thermal conditions for each lake. We include all supporting lake
      specific model parameters, meteorological drivers, and archived code for the
      model and derived metric calculations. This unique dataset offers landscape-level
      insight into the impact of climate change on lakes.

PMID- 28440791
TI  - A curated database of cyanobacterial strains relevant for modern taxonomy and
      phylogenetic studies.
AB  - The dataset herein described lays the groundwork for an online database of
      relevant cyanobacterial strains, named CyanoType
      (http://lege.ciimar.up.pt/cyanotype). It is a database that includes categorized
      cyanobacterial strains useful for taxonomic, phylogenetic or genomic purposes,
      with associated information obtained by means of a literature-based curation. The
      dataset lists 371 strains and represents the first version of the database
      (CyanoType v.1). Information for each strain includes strain synonymy and/or co
      identity, strain categorization, habitat, accession numbers for molecular data,
      taxonomy and nomenclature notes according to three different classification
      schemes, hierarchical automatic classification, phylogenetic placement according
      to a selection of relevant studies (including this), and important bibliographic
      references. The database will be updated periodically, namely by adding new
      strains meeting the criteria for inclusion and by revising and adding up-to-date
      metadata for strains already listed. A global 16S rDNA-based phylogeny is
      provided in order to assist users when choosing the appropriate strains for their
      studies.

PMID- 28440793
TI  - Wavelength-Dependent Plasmon-Mediated Coalescence of Two Gold Nanorods.
AB  - Plasmon-mediated coalescence of two nearby gold nanorods (NRs) suspended in water
      induced by the illumination of a linearly polarized (LP) light was studied
      theoretically. We analyzed the coupled optical forces and torques in terms of
      Maxwell's stress tensor upon two identical NRs irradiated by a LP plane wave
      using the multiple multipole method to estimate the optomechanical outcome.
      Numerical results show that the light-matter interaction can perform attraction
      or repulsion, depending on their initial configurations. For the attraction, the
      end-to-end or side-by-side coalescence of the two gold NRs could be caused by the
      LP light, depending on the wavelength. For example, the side-by-side coalescence
      of two adjacent NRs of r = 15 nm and L = 120 nm is most likely induced by 800-nm
      LP laser beam, whereas the end-to-end coalescence by 1064-nm or 1700-nm LP laser.
      These distinct phenomena are attributed to the perpendicular or parallel
      alignment of NR to the polarization of LP light in different wavelength ranges.
      The magnitude of optical force, proportional to the light's fluence, could be
      stronger than van der Waals force. The estimation based on quasi-static model
      without considering the fluid dynamics may provide an insight to optical
      manipulation on the self-assembly of gold colloid.

PMID- 28440792
TI  - An extra-uterine system to physiologically support the extreme premature lamb.
AB  - In the developed world, extreme prematurity is the leading cause of neonatal
      mortality and morbidity due to a combination of organ immaturity and iatrogenic
      injury. Until now, efforts to extend gestation using extracorporeal systems have
      achieved limited success. Here we report the development of a system that
      incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via
      an umbilical cord interface that is maintained within a closed 'amniotic fluid'
      circuit that closely reproduces the environment of the womb. We show that fetal
      lambs that are developmentally equivalent to the extreme premature human infant
      can be physiologically supported in this extra-uterine device for up to 4 weeks.
      Lambs on support maintain stable haemodynamics, have normal blood gas and
      oxygenation parameters and maintain patency of the fetal circulation. With
      appropriate nutritional support, lambs on the system demonstrate normal somatic
      growth, lung maturation and brain growth and myelination.

PMID- 28440794
TI  - Se-SAD serial femtosecond crystallography datasets from selenobiotinyl
      streptavidin.
AB  - We provide a detailed description of selenobiotinyl-streptavidin (Se-B SA) co
      crystal datasets recorded using the Coherent X-ray Imaging (CXI) instrument at
      the Linac Coherent Light Source (LCLS) for selenium single-wavelength anomalous
      diffraction (Se-SAD) structure determination. Se-B SA was chosen as the model
      system for its high affinity between biotin and streptavidin where the sulfur
      atom in the biotin molecule (C10H16N2O3S) is substituted with selenium. The
      dataset was collected at three different transmissions (100, 50, and 10%) using a
      serial sample chamber setup which allows for two sample chambers, a front chamber
      and a back chamber, to operate simultaneously. Diffraction patterns from Se-B SA
      were recorded to a resolution of 1.9 A. The dataset is publicly available through
      the Coherent X-ray Imaging Data Bank (CXIDB) and also on LCLS compute nodes as a
      resource for research and algorithm development.

PMID- 28440795
TI  - Multimodal chest surface motion data for respiratory and cardiovascular
      monitoring applications.
AB  - Chest surface motion is of significant importance as it contains information of
      respiratory and cardiac systems together with the complex coupling between these
      two systems. Chest surface motion is not only critical in radiotherapy, but also
      useful in personalized systems for continuous cardiorespiratory monitoring. In
      this dataset, a multimodal setup is employed to simultaneously acquire
      cardiorespiratory signals. These signals include high-density trunk surface
      motion (from 16 distinct locations) with VICON motion capture system, nasal
      breathing from a thermal sensor, respiratory effort from a strain belt and
      electrocardiogram in lead-II configuration. This dataset contains 72 trials
      recorded from 11 participants with a cumulative duration of approximately 215 min
      under various conditions such as normal breathing, breath-hold, irregular
      breathing and post-exercise recovery. The presented dataset is not only useful
      for evaluating prediction algorithms for radiotherapy applications, but can also
      be employed for the development of techniques to evaluate the cardio-mechanics
      and hemodynamic parameters of chest surface motion.

PMID- 28440796
TI  - The importance of international collaboration for rare diseases research: a
      European perspective.
AB  - Over the last two decades, important contributions were made at national,
      European and international levels to foster collaboration into rare diseases
      research. The European Union (EU) has put much effort into funding rare diseases
      research, encouraging national funding organizations to collaborate together in
      the E-Rare program, setting up European Reference Networks for rare diseases and
      complex conditions, and initiating the International Rare Diseases Research
      Consortium (IRDiRC) together with the National Institutes of Health in the USA.
      Co-ordination of the activities of funding agencies, academic researchers,
      companies, regulatory bodies, and patient advocacy organizations and partnerships
      with, for example, the European Research Infrastructures maximizes the collective
      impact of global investments in rare diseases research. This contributes to
      accelerating progress, for example, in faster diagnosis through enhanced
      discovery of causative genes, better understanding of natural history of rare
      diseases through creation of common registries and databases and boosting of
      innovative therapeutic approaches. Several examples of funded pre-clinical and
      clinical gene therapy projects show that integration of multinational and
      multidisciplinary expertize generates new knowledge and can result in multicentre
      gene therapy trials. International collaboration in rare diseases research is key
      to improve the life of people living with a rare disease.

PMID- 28440797
TI  - Potential mechanisms of microRNA-141-3p to alleviate chronic inflammatory pain by
      downregulation of downstream target gene HMGB1: in vitro and in vivo studies.
AB  - The present study aimed to investigate the potential role of microRNA-141-3p (miR
      141-3p) in chronic inflammatory pain (CIP) by targeting the high-mobility group
      box1 (HMGB1) gene. In the in vitro study, BV2 microglial cells were selected and
      assigned into blank, lipopolysaccharide (LPS), miR-141-3p mimics, mimics control,
      miR-141-3p inhibitor, inhibitor control, miR-141-3p mimics+LPS, mimics control+
      LPS, miR-141-3p inhibitor+LPS and inhibitor control+LPS groups. Ninety-six rats
      were randomly divided into 8 groups (12 rats in each group): blank control, model
      control, negative control (NC), miR-141-3p mimics+ complete Freund's adjuvant
      (CFA), mimics control+CFA, HMGB1 short hairpin RNA (shRNA)+CFA, HMGB1 NC+CFA and
      miR-141-3p mimics+HMGB1 shRNA+CFA groups. The quantitative real-time PCR, western
      blotting, enzyme-linked immunosorbent assay and pain behavioral test were used to
      measure the miR-141-3p and HMGB1 mRNA expressions, HMGB1 protein expression,
      inflammatory cytokines levels, and thermal and mechanical pain thresholds,
      respectively. Compared with the blank, mimics control, inhibitor control and miR
      141-3p mimics+LPS groups, the miR-141-3p mimics group had increased miR-141-3p
      expression and interleukin (IL)-10 levels, and had decreased mRNA and protein
      expressions of HMGB1 and the levels of IL-1beta, tumor necrosis factor-alpha (TNF
      alpha) and IL-6, whereas the opposite trend were found in the LPS, miR-141-3p
      inhibitor, mimics control+LPS and inhibitor control+LPS groups. Compared with the
      LPS, miR-141-3p inhibitor, mimics control+LPS and inhibitor control+LPS groups,
      the miR141-3p+LPS group had an obviously decreased expression of miR-141-3p and
      IL-10, increased mRNA and protein expressions of HMGB1 and the levels of IL
      1beta, TNF-alpha and IL-6. Compared with the rats in the blank control group, the
      miR-141-3p expression, IL-10 level, and thermal and mechanical pain thresholds
      decreased significantly, whereas the mRNA and protein expressions of HMGB1, IL
      1beta, TNF-alpha and IL-6 increased significantly in rats in the NC, mimics
      control+CFA and HMGB1 NC+ CFA groups. The miR-141-3p expression was increased in
      rats in the miR-141-3p mimics+HMGB1 shRNA+CFA group. Our study demonstrated that
      miR-141-3p can alleviate the CIP by downregulating the downstream target gene
      HMGB1.

PMID- 28440798
TI  - Improved gene delivery to adult mouse spinal cord through the use of engineered
      hybrid adeno-associated viral serotypes.
AB  - Adeno-associated viral (AAV) vectors are often used in gene therapy for
      neurological disorders because of its safety profile and promising results in
      clinical trials. One challenge to AAV gene therapy is effective transduction of
      large numbers of the appropriate cell type, which can be overcome by modulating
      the viral capsid through DNA shuffling. Our previous study demonstrates that
      Rec2, among a family of novel engineered hybrid capsid serotypes (Rec1~4)
      transduces adipose tissue with far superior efficiency than naturally occurring
      AAV serotypes. Here we assessed the transduction of adult spinal cord at two
      different doses of AAV vectors expressing green fluorescent protein (2 * 109 or 4
      * 108 viral particles) via intraparenchymal injection at the thoracic vertebral
      level T9. In comparison with an equal dose of the currently preferable AAV9
      serotype, Rec3 serotype transduced a broader region of the spinal cord up to ~1.5
      cm longitudinally and displayed higher transgene expression and increased maximal
      transduction rates of astrocytes at either dose and neurons at the lower dose.
      These novel engineered hybrid vectors could provide powerful tools at lower
      production costs to manipulate gene expression in the spinal cord for mechanistic
      studies or provide potent vehicles for gene therapy delivery, such as
      neurotrophins, to the spinal cord.

PMID- 28440799
TI  - Corrigendum: KIF3A binds to beta-arrestin for suppressing Wnt/beta-catenin
      signalling independently of primary cilia in lung cancer.

PMID- 28440800
TI  - The Trichodesmium consortium: conserved heterotrophic co-occurrence and genomic
      signatures of potential interactions.
AB  - The nitrogen (N)-fixing cyanobacterium Trichodesmium is globally distributed in
      warm, oligotrophic oceans, where it contributes a substantial proportion of new N
      and fuels primary production. These photoautotrophs form macroscopic colonies
      that serve as relatively nutrient-rich substrates that are colonized by many
      other organisms. The nature of these associations may modulate ocean N and carbon
      (C) cycling, and can offer insights into marine co-evolutionary mechanisms. Here
      we integrate multiple omics-based and experimental approaches to investigate
      Trichodesmium-associated bacterial consortia in both laboratory cultures and
      natural environmental samples. These efforts have identified the conserved
      presence of a species of Gammaproteobacteria (Alteromonas macleodii), and enabled
      the assembly of a near-complete, representative genome. Interorganismal
      comparative genomics between A. macleodii and Trichodesmium reveal potential
      interactions that may contribute to the maintenance of this association involving
      iron and phosphorus acquisition, vitamin B12 exchange, small C compound
      catabolism, and detoxification of reactive oxygen species. These results identify
      what may be a keystone organism within Trichodesmium consortia and support the
      idea that functional selection has a major role in structuring associated
      microbial communities. These interactions, along with likely many others, may
      facilitate Trichodesmium's unique open-ocean lifestyle, and could have broad
      implications for oligotrophic ecosystems and elemental cycling.

PMID- 28440803
TI  - Upstream current for a downstream flow.

PMID- 28440801
TI  - Dispersal timing and drought history influence the response of bacterioplankton
      to drying-rewetting stress.
AB  - The extent and frequency of drought episodes is expected to increase in the
      following decades making it a crucial stress factor for smaller water bodies.
      However, very little is known about how bacterioplankton is affected by increased
      evaporation and how these communities reassemble after rewetting. Here, we
      present results from a microcosm experiment that assessed the effect of drying
      rewetting stress on bacterioplankton in the light of the stress history and the
      rate and timing of dispersal after the rewetting. We found that the drying phase
      resulted mainly in a change of function, whereas the complete desiccation and
      rewetting processes strongly affected both composition and function, which were,
      however, influenced by the initial conditions and stress history of the
      communities. Effects of dispersal were generally stronger when it occurred at an
      early stage after the rewetting. At this stage, selective establishment of
      dispersed bacteria coupled with enhanced compositional and functional recovery
      was found, whereas effects of dispersal were neutral, that is, predictable by
      dispersal rates, at later stages. Our studies therefore show that both the stress
      history and the timing of dispersal are important factors that influence the
      response of bacterial communities to environmental change and stress events.

PMID- 28440802
TI  - Genetic hurdles limit the arms race between Prochlorococcus and the T7-like
      podoviruses infecting them.
AB  - Phages and hosts coexist in nature with a high degree of population diversity.
      This is often explained through coevolutionary models, such as the arms race or
      density-dependent fluctuating selection, which differ in assumptions regarding
      the emergence of phage mutants that overcome host resistance. Previously,
      resistance in the abundant marine cyanobacterium, Prochlorococcus, was found to
      occur frequently. However, little is known about the ability of phages to
      overcome this resistance. Here we report that, in some cases, T7-like cyanophage
      mutants emerge to infect resistant Prochlorococcus strains. These resistance
      breaking phages retained the ability to infect the wild-type host. However,
      fitness of the mutant phages differed on the two hosts. Furthermore, in one case,
      resistance-breaking was accompanied by costs of decreased fitness on the wild
      type host and decreased adsorption specificity, relative to the wild-type phage.
      In two other cases, fitness on the wild-type host increased. Whole-genome
      sequencing revealed mutations in probable tail-related genes. These were highly
      diverse in isolates and natural populations of T7-like cyanophages, suggesting
      that antagonistic coevolution enhances phage genome diversity. Intriguingly, most
      interactions did not yield resistance-breaking phages. Thus, resistance mutations
      raise genetic barriers to continuous arms race cycles and are indicative of an
      inherent asymmetry in coevolutionary capacity, with hosts having the advantage.
      Nevertheless, phages coexist with hosts, which we propose relies on combined,
      parallel action of a limited arms race, fluctuating selection and passive host
      switching within diverse communities. Together, these processes generate a
      constantly changing network of interactions, enabling stable coexistence between
      hosts and phages in nature.

PMID- 28440804
TI  - Monkeys face face distortions.

PMID- 28440806
TI  - Cerebellar granule cells expand their talents.

PMID- 28440807
TI  - Showing transmitters the door: synucleins accelerate vesicle release.

PMID- 28440805
TI  - Cell transplantation therapy for spinal cord injury.
AB  - Spinal cord injury can lead to severe motor, sensory and autonomic dysfunction.
      Currently, there is no effective treatment for the injured spinal cord. The
      transplantation of Schwann cells, neural stem cells or progenitor cells,
      olfactory ensheathing cells, oligodendrocyte precursor cells and mesenchymal stem
      cells has been investigated as potential therapies for spinal cord injury.
      However, little is known about the mechanisms through which these individual cell
      types promote repair and functional improvements. The five most commonly proposed
      mechanisms include neuroprotection, immunomodulation, axon regeneration, neuronal
      relay formation and myelin regeneration. A better understanding of the mechanisms
      whereby these cells promote functional improvements, as well as an appreciation
      of the obstacles in implementing these therapies and effectively modeling spinal
      cord injury, will be important to make cell transplantation a viable clinical
      option and may lead to the development of more targeted therapies.

PMID- 28440808
TI  - Automated and manual patch clamp data of human induced pluripotent stem cell
      derived dopaminergic neurons.
AB  - Human induced pluripotent stem cells can be differentiated into dopaminergic
      neurons (Dopa.4U). Dopa.4U neurons expressed voltage-gated NaV and KV channels
      and showed neuron-like spontaneous electrical activity. In automated patch clamp
      measurements with suspended Dopa.4U neurons, delayed rectifier K+ current
      (delayed KV) and rapidly inactivating A-type K+ current (fast KV) were
      identified. Examination of the fast KV current with inhibitors yielded IC50
      values of 0.4 mM (4-aminopyridine) and 0.1 mM (tetraethylammonium). In manual
      patch clamp measurements with adherent Dopa.4U neurons, fast KV current could not
      be detected, while the delayed KV current showed an IC50 of 2 mM for 4
      aminopyridine. The NaV channels in adherent and suspended Dopa.4U neurons showed
      IC50 values for tetrodotoxin of 27 and 2.9 nM, respectively. GABA-induced
      currents that could be observed in adherent Dopa.4U neurons could not be detected
      in suspended cells. Application of current pulses induced action potentials in
      approx. 70 % of the cells. Our results proved the feasibility of automated
      electrophysiological characterization of neuronal cells.

PMID- 28440809
TI  - A missense polymorphism in the putative pheromone receptor gene VN1R1 is
      associated with sociosexual behavior.
AB  - Pheromones regulate social and reproductive behavior in most mammalian species.
      These effects are mediated by the vomeronasal and main olfactory systems. Effects
      of putative pheromones on human neuroendocrine activity, brain activity and
      attractiveness ratings suggest that humans may communicate via similar
      chemosignaling. Here we studied two samples of younger and older individuals,
      respectively, with respect to one nonsynonymous polymorphism in the gene encoding
      the human vomeronasal type-1 receptor 1, VN1R1, and one nonsynonymous
      polymorphism in the gene encoding the olfactory receptor OR7D4. Participants in
      both samples had self-reported their sociosexual behavior using the sociosexual
      orientation inventory, including questions regarding lifetime number of one-night
      stands, number of partners last year and expected number of partners the coming 5
      years. In women, there was a significant association between the VN1R1
      polymorphism and sociosexual behavior in both samples, driven specifically by the
      question regarding one-night stands. Our results support the hypothesis that
      human social interaction is modulated by communication via chemosignaling.

PMID- 28440810
TI  - Naltrexone modulates dopamine release following chronic, but not acute
      amphetamine administration: a translational study.
AB  - The opioid antagonist naltrexone has been shown to attenuate the subjective
      effects of amphetamine. However, the mechanisms behind this modulatory effect are
      currently unknown. We hypothesized that naltrexone would diminish the striatal
      dopamine release induced by amphetamine, which is considered an important
      mechanism behind many of its stimulant properties. We used positron emission
      tomography and the dopamine D2-receptor radioligand [11C]raclopride in healthy
      subjects to study the dopaminergic effects of an amphetamine injection after
      pretreatment with naltrexone or placebo. In a rat model, we used microdialysis to
      study the modulatory effects of naltrexone on dopamine levels after acute and
      chronic amphetamine exposure. In healthy humans, naltrexone attenuated the
      subjective effects of amphetamine, confirming our previous results. Amphetamine
      produced a significant reduction in striatal radioligand binding, indicating
      increased levels of endogenous dopamine. However, there was no statistically
      significant effect of naltrexone on dopamine release. The same pattern was
      observed in rats, where an acute injection of amphetamine caused a significant
      rise in striatal dopamine levels, with no effect of naltrexone pretreatment.
      However, in a chronic model, naltrexone significantly attenuated the dopamine
      release caused by reinstatement of amphetamine. Collectively, these data suggest
      that the opioid system becomes engaged during the more chronic phase of drug use,
      evidenced by the modulatory effect of naltrexone on dopamine release following
      chronic amphetamine administration. The importance of opioid-dopamine
      interactions in the reinforcing and addictive effects of amphetamine is
      highlighted by the present findings and may help to facilitate medication
      development in the field of stimulant dependence.

PMID- 28440811
TI  - Evaluation of circadian phenotypes utilizing fibroblasts from patients with
      circadian rhythm sleep disorders.
AB  - We evaluated the circadian phenotypes of patients with delayed sleep-wake phase
      disorder (DSWPD) and non-24-hour sleep-wake rhythm disorder (N24SWD), two
      different circadian rhythm sleep disorders (CRSDs) by measuring clock gene
      expression rhythms in fibroblast cells derived from individual patients. Bmal1
      luciferase (Bmal1-luc) expression rhythms were measured in the primary fibroblast
      cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well
      as control subjects. The period length of the Bmal1-luc rhythm (in vitro period)
      was distributed normally and was 22.80+/-0.47 (mean+/-s.d.) h in control-derived
      fibroblasts. The in vitro periods in DSWPD-derived fibroblasts and N24SWD-derived
      fibroblasts were 22.67+/-0.67 h and 23.18+/-0.70 h, respectively. The N24SWD
      group showed a significantly longer in vitro period than did the control or DSWPD
      group. Furthermore, in vitro period was associated with response to chronotherapy
      in the N24SWD group. Longer in vitro periods were observed in the non-responders
      (mean+/-s.d.: 23.59+/-0.89 h) compared with the responders (mean+/-s.d.: 22.97+/
      0.47 h) in the N24SWD group. Our results indicate that prolonged circadian
      periods contribute to the onset and poor treatment outcome of N24SWD. In vitro
      rhythm assays could be useful for predicting circadian phenotypes and clinical
      prognosis in patients with CRSDs.

PMID- 28440812
TI  - Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a
      randomized, double-blind, placebo-controlled, laboratory study.
AB  - Baclofen has been suggested as a potential pharmacotherapy for alcohol use
      disorder, but the clinical data are conflicting. Here we investigated the
      biobehavioral effects of baclofen in a sample of anxious alcohol-dependent
      individuals. This was a randomized, double-blind, placebo-controlled, human
      laboratory study in non-treatment seeking alcohol-dependent individuals with high
      trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo
      for at least 8 days, then performed an experimental session consisting of alcohol
      cue-reactivity followed by alcohol administration procedure (alcohol priming,
      then alcohol self-administration). Total amount of alcohol self-administered was
      the primary outcome; alcohol craving, subjective/physiological responses and
      mood/anxiety symptoms were also evaluated. There was no significant medication
      effect on the total amount of alcohol consumed during the alcohol self
      administration (P=0.76). Baclofen blunted the positive association between
      maximum breath alcohol concentration during priming and the amount of alcohol
      consumption (significant interaction, P=0.03). Ratings of feeling intoxicated
      were significantly higher in the baclofen group after consuming the priming drink
      (P=0.006). During the self-administration session, baclofen significantly
      increased ratings of feeling high (P=0.01) and intoxicated (P=0.01). A
      significant reduction in heart rate (P<0.001) and a trend-level increase in
      diastolic blood pressure (P=0.06) were also detected in the baclofen group during
      the alcohol laboratory session. In conclusion, baclofen was shown to affect
      subjective and physiological responses to alcohol drinking in anxious alcohol
      dependent individuals. These results do not support an anti-craving or anti
      reinforcing effect of baclofen, but rather suggest that baclofen may act as a
      substitution medication for alcohol use disorder.

PMID- 28440813
TI  - Instability of default mode network connectivity in major depression: a two
      sample confirmation study.
AB  - Major depression is associated with altered static functional connectivity in
      various brain networks, particularly the default mode network (DMN). Dynamic
      functional connectivity is a novel tool with little application in affective
      disorders to date, and holds the potential to unravel fluctuations in
      connectivity strength over time in major depression. We assessed stability of
      connectivity in major depression between the medial prefrontal cortex (mPFC) and
      posterior cingulate cortex (PCC), key nodes in the DMN that are implicated in
      ruminative cognitions. Functional connectivity stability between the mPFC and PCC
      over the course of a resting-state functional magnetic resonance imaging (fMRI)
      scan was compared between medication-free patients with major depression and
      healthy controls matched for age, sex and handedness. We tested replicability of
      the results in an independent sample using multi-echo resting-state fMRI. The
      primary sample included 20 patients and 19 controls, while the validation sample
      included 19 patients and 19 controls. Greater connectivity variability was
      detected in major depression between mPFC and PCC. This was demonstrated in both
      samples indicating that the results were reliable and were not influenced by the
      fMRI acquisition approach used. Our results demonstrate that alterations within
      the DMN in major depression go beyond changes in connectivity strength and extend
      to reduced connectivity stability within key DMN regions. Findings were robustly
      replicated across two independent samples. Further research is necessary to
      better understand the nature of these fluctuations in connectivity and their
      relationship to the aetiology of major depression.

PMID- 28440814
TI  - Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice
      induces behavioural and biological changes relevant to depression.
AB  - Numerous studies have examined links between postnatal neurogenesis and
      depression using a range of experimental methods to deplete neurogenesis. The
      antimitotic drug temozolomide (TMZ) has previously been used successfully as an
      experimental tool in animals to deplete adult neurogenesis and is used regularly
      on human patients as a standard chemotherapy for brain cancer. In this study, we
      wanted to evaluate whether TMZ as a model for chemotherapy treatment could affect
      parameters related to depression in an animal model. Prevalence rates of
      depression in patients is thought to be highly underdiagnosed, with some studies
      reporting rates as high as 90%. Results from this study in mice, treated with a
      regimen of TMZ similar to humans, exhibited behavioural and biochemical changes
      that have relevance to the development of depression. In particular, behavioural
      results demonstrated robust deficits in processing novelty and a significant
      increase in the corticosterone response. Quantification of neurogenesis using a
      novel sectioning method, which clearly evaluates dorsal and ventral neurogenesis
      separately, showed a significant correlation between the level of ventral
      neurogenesis and the corticosterone response. Depression is a complex disorder
      with discoveries regarding its neurobiology and how it relates to behaviour being
      only in their infancy. The findings presented in this study demonstrate that
      chemotherapy-induced decreases in neurogenesis results in previously unreported
      behavioural and biochemical consequences. These results, we argue, are indicative
      of a biological mechanism, which may contribute to the development of depression
      in patients being treated with chemotherapy and is separate from the mental
      distress resulting from a cancer diagnosis.

PMID- 28440818
TI  - Corrigendum: An association between time-varying serum alkaline phosphatase
      concentrations and mortality rate in patients undergoing peritoneal dialysis: a
      five-year cohort study.

PMID- 28440815
TI  - 15q11.2 CNV affects cognitive, structural and functional correlates of dyslexia
      and dyscalculia.
AB  - Several copy number variants have been associated with neuropsychiatric disorders
      and these variants have been shown to also influence cognitive abilities in
      carriers unaffected by psychiatric disorders. Previously, we associated the
      15q11.2(BP1-BP2) deletion with specific learning disabilities and a larger corpus
      callosum. Here we investigate, in a much larger sample, the effect of the
      15q11.2(BP1-BP2) deletion on cognitive, structural and functional correlates of
      dyslexia and dyscalculia. We report that the deletion confers greatest risk of
      the combined phenotype of dyslexia and dyscalculia. We also show that the
      deletion associates with a smaller left fusiform gyrus. Moreover, tailored
      functional magnetic resonance imaging experiments using phonological lexical
      decision and multiplication verification tasks demonstrate altered activation in
      the left fusiform and the left angular gyri in carriers. Thus, by using
      convergent evidence from neuropsychological testing, and structural and
      functional neuroimaging, we show that the 15q11.2(BP1-BP2) deletion affects
      cognitive, structural and functional correlates of both dyslexia and dyscalculia.

PMID- 28440819
TI  - Amphiphilic carbon dots as versatile vectors for nucleic acid and drug delivery.
AB  - Carbon dot (CD)-based multifunctional delivery systems have shown great potential
      in both drug/gene delivery and bio-imaging. In this work, we present a strategy
      to simply construct amphiphilic CDs (ACDs) by conjugating hydrophobic alkyl
      epoxide to the surface amino groups of PEI 600-derived CDs. ACDs could well
      dissolve in water or organic solvents and emit bright fluorescence both in
      solutions and cells. 1HNMR also suggested that ACDs may form micelle-like
      structures in water, and their CMC could be determined. Enhanced green
      fluorescent protein (EGFP) expression and flow cytometry experiments showed that
      ACDs have higher transfection efficiency than Lipofectamine 2000 in A549 cells.
      Besides DNA, ACDs could also effectively transfect Sur siRNA toward A549 cells
      and cause early cell apoptosis. The 3D multicellular spheroids further confirmed
      their high potential for delivering therapeutic genes into the tumor tissue. On
      the other hand, ACDs also exhibited good drug loading ability. CLSM experiment
      results showed that DOX could be effectively internalized by the cell and slowly
      released from the drug/ACD complex. These results suggest that ACDs may not only
      serve as versatile delivery vectors with potential for applications in clinical
      cancer treatment, but also offer an inspiration for the discovery of CD-based
      gene/drug delivery systems.

PMID- 28440816
TI  - Influences of prenatal and postnatal maternal depression on amygdala volume and
      microstructure in young children.
AB  - Maternal depressive symptoms influence neurodevelopment in the offspring. Such
      effects may appear to be gender-dependent. The present study examined
      contributions of prenatal and postnatal maternal depressive symptoms to the
      volume and microstructure of the amygdala in 4.5-year-old boys and girls.
      Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal
      Depression Scale (EPDS) at 26 weeks of gestation. Postnatal maternal depression
      was assessed at 3 months using the EPDS and at 1, 2, 3 and 4.5 years using the
      Beck's Depression Inventory-II. Structural magnetic resonance imaging and
      diffusion tensor imaging were performed with 4.5-year-old children to extract the
      volume and fractional anisotropy (FA) values of the amygdala. Our results showed
      that greater prenatal maternal depressive symptoms were associated with larger
      right amygdala volume in girls, but not in boys. Increased postnatal maternal
      depressive symptoms were associated with higher right amygdala FA in the overall
      sample and girls, but not in boys. These results support the role of variation in
      right amygdala structure in transmission of maternal depression to the offspring,
      particularly to girls. The differential effects of prenatal and postnatal
      maternal depressive symptoms on the volume and FA of the right amygdala suggest
      the importance of the timing of exposure to maternal depressive symptoms in brain
      development of girls. This further underscores the need for intervention
      targeting both prenatal and postnatal maternal depression to girls in preventing
      adverse child outcomes.

PMID- 28440817
TI  - Effects of dopamine D2/D3 receptor antagonism on human planning and spatial
      working memory.
AB  - Psychopharmacological studies in humans suggest important roles for dopamine (DA)
      D2 receptors in human executive functions, such as cognitive planning and spatial
      working memory (SWM). However, studies that investigate an impairment of such
      functions using the selective DA D2/3 receptor antagonist sulpiride have yielded
      inconsistent results, perhaps because relatively low doses were used. We believe
      we report for the first time, the effects of a higher (800 mg p.o.) single dose
      of sulpiride as well as of genetic variation in the DA receptor D2 gene (DA
      receptor D2 Taq1A polymorphism), on planning and working memory. With 78 healthy
      male volunteers, we apply a between-groups, placebo-controlled design. We measure
      outcomes in the difficult versions of the Cambridge Neuropsychological Test
      Automated Battery One-Touch Stockings of Cambridge and the self-ordered SWM task.
      Volunteers in the sulpiride group showed significant impairments in planning
      accuracy and, for the more difficult problems, in SWM. Sulpiride administration
      speeded response latencies in the planning task on the most difficult problems.
      Volunteers with at least one copy of the minor allele (A1+) of the DA receptor D2
      Taq1A polymorphism showed better SWM capacity, regardless of whether they
      received sulpiride or placebo. There were no effects on blood pressure, heart
      rate or subjective sedation. In sum, a higher single dose of sulpiride impairs
      SWM and executive planning functions, in a manner independent of the DA receptor
      D2 Taq1A polymorphism.

PMID- 28440820
TI  - A pre-strain strategy for developing a highly stretchable and foldable one
      dimensional conductive cord based on a Ag nanowire network.
AB  - A highly stretchable and foldable conductive cord was developed by depositing
      silver nanowires (AgNWs) on a polyurethane cord. The application of pre-strain to
      the cord during the deposition of AgNWs resulted in the formation of a wrinkled
      AgNW layer, thereby inducing structural stability towards stretching and bending.
      This conductive cord exhibited stable electric conduction under strain values of
      up to 167% and at a bending radius of 0.3 mm. Also, it could withstand a
      stretching test of 500 cycles at a strain of 50%.

PMID- 28440822
TI  - A carbonyl reductase from Candida parapsilosis ATCC 7330: substrate selectivity
      and enantiospecificity.
AB  - Candida parapsilosis ATCC 7330, a rich source of highly stereospecific
      oxidoreductases, catalyzes oxidation-reduction of a plethora of compounds
      yielding industrially important intermediates. An (S)-specific carbonyl reductase
      (SRED) purified and characterized from this yeast is reported here. (R)-Specific
      carbonyl reductase (CpCR) was reported by us earlier. SRED asymmetrically reduces
      ketones with excellent enantiospecificity (ee > 99%) and alpha-ketoesters with
      higher catalytic activity but moderate enantiospecificity (ee 70%) in the
      presence of NADPH. Minimal activity is shown towards the reduction of aldehydes.
      While the reduction of alpha-ketoesters with SRED can occur with either NADPH or
      NADH, for ketone reduction SRED requires NADPH specifically. SRED with a subunit
      molecular weight of 30 kDa shows optimal activity at pH 5.0 and 25  degrees C,
      and its activity is affected by Cu2+. Taken together, SRED and CpCR offer
      substrates which on asymmetric reduction give products of opposite absolute
      configurations.

PMID- 28440821
TI  - DFT-D3 study of H2 and N2 chemisorption over cobalt promoted Ta3N5-(100), (010)
      and (001) surfaces.
AB  - The reactants for ammonia synthesis have been studied, employing density
      functional theory (DFT), with respect to their adsorption on tantalum nitride
      surfaces. The adsorption of nitrogen was found to be mostly molecular and non
      activated with side-on, end-on and tilt configurations. At bridging nitrogen
      sites (Ta-N-Ta) it results in an azide functional group formation with a
      formation energy of 205 kJ mol-1. H2 was found also to chemisorb molecularly with
      an adsorption energy in the range -81 to -91 kJ mol-1. At bridging nitrogen sites
      it adsorbs dissociatively forming >NH groups with an exothermic formation energy
      of -175 kJ mol-1 per H2. The nitrogen vacancy formation energies were relatively
      high compared to other metal nitrides found to be 2.89 eV, 2.32 eV and 1.95 eV
      for plain, surface co-adsorbed cobalt and sub-surface co-adsorbed cobalt Ta3N5
      (010). Co-adsorption of cobalt was found to occur mostly at nitrogen rich sites
      of the surface with an adsorption energy that ranged between -200 to -400 kJ mol
      1. The co-adsorption of cobalt was found to enhance the dissociation of molecular
      hydrogen on the surface of Ta3N5. The studies offer significant new insight with
      respect to the chemistry of N2 and H2 with tantalum nitride surfaces in the
      presence of cobalt promoters.

PMID- 28440823
TI  - Quantitative NMR of quadrupolar nucleus as a novel analytical method: hydrolysis
      behaviour analysis of aluminum ion.
AB  - In this study, quantitative nuclear magnetic resonance (qNMR) spectroscopy of
      quadrupolar nuclei has been established. The complicated hydrolysis behavior of
      the Al3+ ion, which causes fish poisoning and inhibits the growth of plants in
      environmental water, was clarified by 27Al qNMR spectroscopy. Highly accurate
      simultaneous multicomponent quantitative analysis of various hydrolyzed forms of
      the Al ion was achieved in a non-destructive manner. The calibration curve of the
      external standard aqueous Al(NO3)3 solution showed excellent linearity over a
      very wide concentration range from 1 * 10-4 to 1 mol L-1 (an increase in
      concentration of 10 000 times), with a simple experimental and analytical
      procedure. Furthermore, the weaknesses of the conventional Ferron assay and the
      advantages of 27Al qNMR spectroscopy were considered. The quantitative
      determination error for the free [Al(H2O)6]3+ ion and the trinuclear complex,
      which has a high complexation rate, is higher in the Ferron assay than in the
      27Al qNMR technique. The concentrations of four Al species were directly
      determined by 27Al qNMR, namely, free [Al(H2O)6]3+, the trinuclear complex,
      Al(OH)4-, and tridecameric hydrolyzed Al, which has a Keggin structure. The
      concentration of the tridecamer rapidly increased until 100 min after NaOH
      addition, and showed a local maximum after 1 week. In addition, the concentration
      of colloidal Al hydroxide, which cannot be detected by NMR spectroscopy, was
      determined by numerical analysis. This species was generated in the initial stage
      of reaction, and then the tridecamer formed very slowly.

PMID- 28440824
TI  - PhI(OAc)2-mediated 1,2-aminohalogenation of alkynes: a general access to (E)-4
      (halomethylene)oxazolidin-2-ones.
AB  - A new PhI(OAc)2-mediated 1,2-aminohalogenation of prop-2-yn-1-yl carbamates and
      various halogen sources is presented with excellent selectivity and high step
      economy. The reaction is general and rapid for the construction of diverse (E)-4
      (halomethylene)oxazolidin-2-ones through the generation of the three-membered
      ring or N-radical followed by intramolecular cyclization.

PMID- 28440825
TI  - Radio frequency negative permittivity in random carbon nanotubes/alumina
      nanocomposites.
AB  - While metal is the most common conductive constituent element in the preparation
      of metamaterials, one-dimensional conductive carbon nanotubes (CNTs) provide
      alternative building blocks. Here alumina (Al2O3) nanocomposites with multi
      walled carbon nanotubes (MWCNTs) uniformly dispersed in the alumina matrix were
      prepared by hot-pressing sintering. As the MWCNT content increased, the formed
      conductive MWCNT networks led to the occurrence of the percolation phenomenon and
      a change of the conductive mechanism. Two different types of negative
      permittivity (i.e., resonance-induced and plasma-like) were observed in the
      composites. The resonance-induced negative permittivity behavior in the composite
      with a low nanotube content was ascribed to the induced electric dipole generated
      from the isolated MWCNTs. The frequency dispersions of such negative permittivity
      can be fitted well by the Lorentz model, while the observed plasma-like negative
      permittivity behavior in the composites with MWCNT content exceeding the
      percolation threshold could be well explained by the low frequency plasmonic
      state generated from conductive nanotube networks using the Drude model. This
      work is favorable to revealing the generation mechanism of negative permittivity
      behavior and will greatly facilitate the practical applications of metamaterials.

PMID- 28440826
TI  - Realization of multiphoton lasing from carbon nanodot microcavities.
AB  - The use of organosilane chains to link carbon nanodots (CDs) through organosilane
      surface functional groups is proposed to improve the efficiency of multiphoton
      absorption. As a result, a large absorption coefficient of 1.16 * 10-6 cm5 per
      GW3 is obtained and four-photon luminescence under 1900 nm excitation is observed
      from the CDs at room temperature. Furthermore, a CD laser, which demonstrates
      random lasing under three-photon (i.e. 1400 nm) excitation, can be realized by
      sandwiching a CD film between a quartz substrate and a dielectric mirror. The
      formation of strongly confined microcavities, which arise from the non-uniform
      distribution of refractive indices inside the CD film, is attributed to the
      realization of lasing emission.

PMID- 28440827
TI  - Molecular dynamics investigations of membrane-bound CYP2C19 polymorphisms reveal
      distinct mechanisms for peripheral variants by long-range effects on the
      enzymatic activity.
AB  - Increasing sophistication in methods used to account for human polymorphisms in
      susceptibility to drug metabolism has been one of the success stories in the
      prevention of adverse drug reactions. Genetic polymorphisms in drug-metabolizing
      enzymes can affect enzyme activity and cause differences in treatment response or
      drug toxicity. CYP2C19 is one of the most highly polymorphic CYP enzymes and acts
      on 10-15% of drugs in current clinical use. Despite the number of experimental
      analyses carried out for this system, the detailed structural basis for altered
      catalytic properties of polymorphic CYP2C19 variants remains unexplained at the
      atomic level. To this end, we have investigated the mutation effects on
      structural characteristics and tunnel geometry upon single point mutations to
      elucidate the underlying molecular mechanism for the enzymatic activity
      deficiencies by using the fully atomistic molecular dynamics (MD) simulations in
      their native, membrane-bound cellular environment. The obtained results
      demonstrate how significant sequence divergence causes heterogeneous variations,
      and further affects the shape and chemical properties of the substrate binding
      site. Principal component analysis (PCA) results combined with free energy
      calculations have revealed distinct mechanisms for different peripheral variants,
      implying a more complicated process for the decrease/loss of enzymatic activity
      upon the introduction of point mutations in CYP2C19 rather than simply structural
      changes of the region where the mutation is located. Overall, our present study
      provides important insights into the current pharmacogenetic knowledge of human
      drug-metabolizing CYP2C19 to understand the large inter-individual variability in
      drug clearance. The knowledge of heterogeneous variations in structural features
      could guide future experimental and computational work on efficient and safe drug
      treatment with better pharmacokinetic properties based on the common variant
      alleles of CYP genes, which varies among different ethnic populations.

PMID- 28440828
TI  - Synthesis, duplex-forming ability, enzymatic stability, and in vitro antisense
      potency of oligonucleotides including 2'-C,4'-C-ethyleneoxy-bridged thymidine
      derivatives.
AB  - We synthesized thymidine derivatives of 2'-C,4'-C-ethyleneoxy-bridged 2'
      deoxyribonucleic acids with an 8'-methyl group ((R)-Me-EoDNA and (S)-Me-EoDNA)
      and without any substituent (EoDNA). Oligonucleotides including these EoDNAs
      showed high hybridization abilities with complementary RNA and excellent
      enzymatic stabilities compared with natural DNA. Moreover, the in vitro antisense
      potency of oligonucleotides with these EoDNAs and our recently reported methylene
      EoDNAs was investigated and compared with that of LNA, which is a practical
      chemical modification for oligonucleotide-therapeutic agents. The results showed
      that EoDNAs and methylene-EoDNAs could be promising candidates for antisense
      technology.

PMID- 28440829
TI  - Ruthenium(ii)-catalyzed ortho-C-H arylation of diverse N-heterocycles with aryl
      silanes by exploiting solvent-controlled N-coordination.
AB  - We report the first method for the direct, regioselective Ru(ii)-catalyzed
      oxidative arylation of C-H bonds in diverse N-heterocycles with aryl silanes by
      exploiting solvent-controlled N-coordination. The reaction takes advantage of the
      attractive features of organosilanes as coupling partners, providing proof of
      concept for N-directed Ru(ii)-catalyzed C-H arylation. This novel, operationally
      simple and versatile protocol utilizes the Ru(ii)/CuF2 reagent system in which
      CuF2 serves as a dual activator/oxidant in non-coordinating solvents to
      accommodate for ligand N-coordination. This first Ru(ii)-catalyzed N-directed
      Hiyama C-H arylation offers broad implications to achieve numerous C-H bond
      functionalizations by versatile ruthenium(ii) catalysis manifold.

PMID- 28440830
TI  - Organocatalytic decarboxylative aldol reaction of beta-ketoacids with alpha
      ketophosphonates en route to the enantioselective synthesis of tertiary alpha
      hydroxyphosphonates.
AB  - The first example of an asymmetric organocatalyzed decarboxylative aldol reaction
      of beta-ketoacids (aroylacetic acids) with alpha-ketophosphonates that produces a
      quaternary chiral centre has been developed. A quinidine based bifunctional urea
      derivative was identified as the preferred catalyst affording gamma-aroyl
      tertiary alpha-hydroxyphosphonates in good yield and enantioselectivity. The 31P
      NMR spectroscopic study was performed to shed light on the reaction mechanism.

PMID- 28440831
TI  - Systematic investigations on fused pi-system compounds of seven benzene rings
      prepared by photocyclization of diphenanthrylethenes.
AB  - We studied the photoproducts of 1-(n-phenanthryl)-2-(m-phenanthryl)ethenes (nEm;
      n, m = 1, 3 and 9) for understanding photocyclization patterns based on NMR
      spectroscopy. The crystal structures of the photoproducts were analyzed by X-ray
      crystallography, and the photophysical features of the photocyclized molecules
      were investigated based on emission and transient absorption measurements.
      Phenanthrene derivatives substituted at the 1- and 3-positions were prepared for
      synthesizing nEm by photocyclization of stilbene derivatives. We obtained four
      types of primary photoproducts (n@m) from the corresponding nEm. Two of them were
      found to have racemic molecular structures in the single crystal determined by X
      ray crystallography. Besides the primary photoproducts, two types of secondary
      photoproducts (n@mPP) were isolated. Fluorescence quantum yields and lifetimes of
      the obtained photoproducts were determined in solution whereas the definite
      fluorescence quantum yields were obtained in the powder. Observation of the
      triplet-triplet absorption spectra in solution by laser photolysis techniques
      showed that intersystem crossing to the triplet state competes with the
      fluorescence process.

PMID- 28440832
TI  - Nanoemitters and innate immunity: the role of surfactants and bio-coronas in
      myeloperoxidase-catalyzed oxidation of pristine single-walled carbon nanotubes.
AB  - Single-walled carbon nanotubes (SWCNTs) are experimentally utilized in in vivo
      imaging and photothermal cancer therapy owing to their unique physicochemical and
      electronic properties. For these applications, pristine carbon nanotubes are
      often modified by polymer surfactant coatings to improve their biocompatibility,
      adding more complexity to their recognition and biodegradation by immuno
      competent cells. Here, we investigate the oxidative degradation of SWCNTs
      catalyzed by neutrophil myeloperoxidase (MPO) using bandgap near-infrared (NIR)
      photoluminescence and Raman spectroscopy. Our results show diameter-dependence at
      the initial stages of the oxidative degradation of sodium cholate-, DNA-, and
      albumin-coated SWCNTs, but not phosphatidylserine-coated SWCNTs. Moreover, sodium
      deoxycholate- and phospholipid-polyethylene glycol coated SWCNTs were not
      oxidized under the same reaction conditions, indicating that a surfactant can
      greatly impact the biodegradability of a nanomaterial. Our data also revealed
      that possible binding between MPO and surfactant coated-SWCNTs was unfavorable,
      suggesting that oxidation is likely caused by a hypochlorite generated through
      halogenation cycles of free MPO, and not MPO bound to the surface of SWCNTs. The
      identification of SWCNT diameters and coatings that retain NIR fluorescence
      during the interactions with the components of an innate immune system is
      important for their applications in in vivo imaging.

PMID- 28440833
TI  - Structure-function studies of acinetobactin analogs.
AB  - Pathogenic Acinetobacter baumannii excrete the siderophore pre-acinetobactin as
      an iron-scavenging virulence factor. Pre-acinetobactin is a 2,3-dihydroxy-phenyl
      oxazoline that undergoes pH-dependent isomerization to the isooxazolidinone form
      acinetobactin in order to expand the pH range for iron acquisition by A.
      baumannii. In this study we establish important structure-function relationships
      for the kinetics of isomerization, iron(iii) binding, and siderophore utilization
      by A. baumannii. We showed that electronic properties of the phenyl oxazoline
      influence isomerization kinetics and iron(iii) binding. We found that iron(iii)
      chelation was directly correlated with A. baumannii utilization. Our studies
      provide important structural and mechanistic insight for understanding how
      pathogenic A. baumannii uses pre-acinetobactin as a 2-for-1 iron-scavenging
      siderophore virulence factor.

PMID- 28440834
TI  - An approximate full-dimensional quantum dynamics study of the mode specificity in
      the dissociative chemisorption of D2O on rigid Cu(111).
AB  - The mode specificity of the dissociative chemisorption of D2O on a rigid Cu(111)
      surface was investigated by calculating the approximate full-dimensional (9D)
      dissociation probabilities with the implementation of the seven-dimensional (7D)
      quantum dynamics calculations and site averaging approximations. The approximate
      9D dissociation probabilities for D2O initially in various vibrational states
      were obtained by averaging the site-specific 7D results over 9 impact sites on an
      accurate 9D potential energy surface (PES). Strong mode specificity was observed
      for the title reaction, where vibrational excitations of the two stretching modes
      of D2O are more efficacious than increasing the translational energy in promoting
      the reaction, while the bending excitations with one and two quanta are less
      efficacious than the same amount of translational energy in enhancing the
      reactivity at low kinetic energies.

PMID- 28440835
TI  - The generation of compartmentalized nanoparticles containing siRNA and cisplatin
      using a multi-needle electrohydrodynamic strategy.
AB  - This study outlines a novel manufacturing technique for the generation of
      compartmentalized trilayered nanoparticles loaded with an anti-cancer agent and
      siRNA as a platform for the combination treatment of cancers. More specifically,
      we describe the use of a multi-needle electrohydrodynamic approach to produce
      nanoparticles with high size specificity and scalable output, while allowing
      suitable environments for each therapeutic agent. The inner polylactic-glycolic
      acid (PLGA) layer was loaded with cisplatin while the middle chitosan layer was
      loaded with siRNA. The corresponding polymeric solutions were characterized for
      their viscosity, surface tension and conductivity, while particle size was
      determined using dynamic light scattering. The internal structure was studied
      using transmission electron microscopy (TEM) and Structured Illumination
      Microscopy (SIM). The inclusion of cisplatin was studied using electron
      dispersive spectroscopy (EDS). We were able to generate nanoparticles of
      approximate size 130 nm with three distinct layers containing an outer protective
      PLGA layer, a middle layer of siRNA and an inner layer of cisplatin. These
      particles have the potential not only for uptake into tumors via the enhanced
      permeability and retention (EPR) effect but also the sequential release of the
      siRNA and chemotherapeutic agent, thereby providing a means of overcoming
      challenges of targeting and tumor drug resistance.

PMID- 28440836
TI  - Controllable hydrothermal synthesis of Ni/H-BEA with a hierarchical core-shell
      structure and highly enhanced biomass hydrodeoxygenation performance.
AB  - Ni based catalysts are wildly used in catalytic industrial processes due to their
      low costs and high activities. The design of highly hierarchical core-shell
      structured Ni/HBEA is achieved using a sustainable, simple, and easy-tunable
      hydrothermal synthesis approach using combined NH4Cl and NH3.H2O as a co
      precipitation agent at 120  degrees C. Starting from a single-crystalline
      hierarchical H+-exchanged beta polymorph zeolite (HBEA), the adjustment of the
      precipitate conditions shows that mixed NH4Cl and NH3.H2O precipitates with
      proper concentrations are vital in the hydrothermal synthesis for preserving a
      good crystalline morphology of HBEA and generating abundant highly-dispersed Ni
      nanoparticles (loading: 41 wt%, 5.9 +/- 0.7 nm) encapsulated onto/into the
      support. NH4Cl solution without an alkali is unable to generate abundant Ni
      nanoparticles from Ni salts under the hydrothermal conditions, whereas NH3.H2O
      seriously damages the pore structure. After studying the in situ changes in
      infrared, X-ray diffractometry, temperature-programmed reduction, and scanning
      electron microscopy measurements, as well as variations in the filtrate pH, Si/Al
      ratios, and solid sample Ni loading, a two-step dissolution-recrystallization
      process is proposed. The process consists of Si dissolution and no change in
      elemental Al, and after the dissolved Si(iv) concentrations have promoted Ni
      phyllosilicate nanosheet solubility, further growth of multilayered Ni
      phyllosilicate nanosheets commences. The precursor Ni phyllosilicate is
      changeable between Ni3Si2O5(OH)4 and Ni3Si4O10(OH)2, because of competition in
      kinetically-favored and thermodynamically-controlled species caused by different
      basic agents. The superior catalytic performance is demonstrated in the
      metal/acid catalyzed biomass derived bulky stearic acid hydrodeoxygenation with
      90% octadecane selectivity and a promising rate of 54 g g-1 h-1, which highly
      excels the reported rates catalyzed by Ni catalysts. Significant improvements in
      activity and selectivity are related to the highly dispersive Ni nanoparticles
      onto/into intra-mesopores of hierarchical HBEA, hence enhance the accessibility
      of bulky substrates to metal sites and mass transfer capacity.

PMID- 28440837
TI  - Modelling of thermal transport through a nanocellular polymer foam: toward the
      generation of a new superinsulating material.
AB  - Superinsulating materials play a pivotal role in achieving the sustainable
      development of our modern world by improving energy efficiency, and reducing
      energy consumption and CO2 emission. Nanocellular polymer foams have been
      considered as a promising superinsulating material, but their development is yet
      to be achieved. The understanding of thermal transport through the nanocellular
      foam is crucial for developing this superinsulating material. Herein, we report
      an accurate mathematical model for the first time to quantitatively estimate
      thermal transport through the nanocellular polymer foam. This is realized by
      taking into account the phonon scattering effect, the Knudsen effect and the thin
      film interference effect in modeling the thermal transport through solid
      conduction, gas conduction and thermal radiation, respectively. We demonstrate a
      quantitative relationship between the cellular structure and the equivalent
      thermal conductivity and present the optimum cellular structure scope for
      achieving the superinsulating performance. In particular, the significance of
      thermal radiation in the nanocellular polymer foam is emphasized. This
      mathematical model offers a very useful tool for deeply understanding thermal
      transport through the nanocellular polymer foams, and guiding the development of
      the new generation of superinsulating materials.

PMID- 28440838
TI  - Detection and sizing of nanoparticles and DNA on PDMS nanofluidic chips based on
      differential resistive pulse sensing.
AB  - The RPS (Resistive Pulse Sensing) technique is a popular tool for the label-free
      detection of particles. This paper describes a simple, cost-effective PDMS
      nanofluidic chip for the detection and characterization of nanoparticles based on
      the differential RPS technique with high resolution and sensitivity. The chip is
      composed of two layers of PDMS slabs. Microchannel systems fabricated by the
      photolithography method on the top layer are used for sample loading and
      differential signal acquisition, and a straight nanochannel on the bottom layer
      fabricated by an unconventional approach bridging the gap between the
      microchannels works as an RPS sensing gate. A single-stage differential amplifier
      is used to amplify the RPS signals when particles or DNA pass through the sensing
      gate. It was demonstrated that this nanofluidic RPS chip can detect nanoparticles
      as small as 23 nm with a high SNR (Signal-to-Noise Ratio). The experimental
      results also show that the device is able to distinguish nanoparticles of smaller
      size differences such as 60 nm and 83 nm with high resolution, showing superior
      performance in comparison with the results obtained from DLS (Dynamic Light
      Scattering). This differential nano-RPS chip was also applied to detect the
      translocation of dsDNA molecules.

PMID- 28440839
TI  - Refugee health and rehabilitation: Challenges and response.
AB  - BACKGROUND: The current global refugee crisis poses major challenges in providing
      effective healthcare to refugees, particularly for non-communicable diseases
      management and disability. This article provides an overview of refugee health
      and potential challenges from the rehabilitation perspective. METHODS: A
      literature search (both academic and grey literature) was conducted using medical
      and health science electronic databases and internet search engines (2001-2016).
      Both authors independently selected studies. Due to heterogeneity amongst
      identified articles, a narrative analysis was performed for best-evidence
      synthesis to outline the current health and rehabilitation status of refugees and
      existing gaps in care. RESULTS: Data suggest that infectious diseases requiring
      treatment in refugees are a minority; whilst non-communicable diseases,
      musculoskeletal conditions are prevalent. Many refugees arrive with complex
      health needs. One in 6 refugees have a physical health problem severely affecting
      their lives and two-thirds experience mental health problems, signifying the
      important role of rehabilitation. Refugees face continued disadvantage, poverty
      and dependence due to lack of cohesive support in their new country, which are
      determinants of both poor physical and mental health. This is compounded by
      language barriers, impoverishment, and lack of familiarity with the local
      environment and healthcare system. In Australia, there are concerns about sexual
      and gender-based violence in off-shore detention camps. Targeted physical and
      cognitive rehabilitative strategies have much to offer these vulnerable people to
      allow for improved activity and participation. CONCLUSION: Strong leadership and
      effective action from national and international bodies is urgently needed to
      develop comprehensive rehabilitation-inclusive medical care for refugees.

PMID- 28440840
TI  - Professionals' perceptions of factors affecting implementation and continuation
      of a physical activity promotion programme in rehabilitation: A qualitative
      study.
AB  - OBJECTIVE: To describe professionals' perceptions of factors that facilitate or
      hamper the implementation and continuation of a physical activity promotion
      programme in rehabilitation. DESIGN: This study used a qualitative design.
      METHODS: Semi-structured interviews (n = 22) were conducted with rehabilitation
      professionals (n = 28) involved in the implementation of a physical activity
      promotion programme. Two additional interviews were conducted with the programme
      coordinators (n = 2). The study involved 18 rehabilitation organizations
      implementing the programme that targets people with disabilities or chronic
      diseases. Organizations were supported in the implementation process by the
      programme coordinators. RESULTS: Commonly perceived facilitating factors were:
      involvement of committed and enthusiastic professionals; agreement with their
      organizations' vision/wishes; the perceived additional value of the programme;
      and opportunities to share knowledge and experience with professionals from other
      organizations. Commonly perceived hampering factors were: uncertainty about
      continuing the programme; limited flexibility; and lack of support from
      physicians and therapists to implement the programme. CONCLUSION: Professionals
      perceived a heterogeneous set of factors that facilitate and/or hamper the
      implementation and continuation of a physical activity promotion programme in
      rehabilitation. Based on these findings, recommendations were formulated to
      enhance embedding of physical activity promotion during and after rehabilitation.

PMID- 28440841
TI  - Rehabilitation after traumatic brain injury: A survey in 70 European neurotrauma
      centres participating in the CENTER-TBI study.
AB  - OBJECTIVE: To describe variation in structural and process characteristics of
      acute in-hospital rehabilitation and referral to post-acute care for patients
      with traumatic brain injury across Europe. DESIGN: Survey study, of neurotrauma
      centres. METHODS: A 14-item survey about in-hospital rehabilitation and referral
      to post-acute care was sent to 71 neurotrauma centres participating in a European
      multicentre study (CENTER-TBI). The questionnaire was developed based on
      literature and expert opinion and was pilot-tested before sending out to the
      centres. RESULTS: Seventy (99%) centres in 20 countries completed the survey. The
      included centres were predominately academic level I trauma centres. Among the 70
      centres, a multidisciplinary rehabilitation team can be consulted at 41% (n = 29)
      of the intensive care units and 49% (n = 34) of the wards. Only 13 (19%) centres
      used rehabilitation guidelines in patients with traumatic brain injury. Age was
      reported as a major determinant of referral decisions in 32 (46%) centres, with
      younger patients usually referred to specialized rehabilitation centres, and
      patients >= 65 years also referred to nursing homes or local hospitals.
      CONCLUSION: Substantial variation exists in structural and process
      characteristics of in-hospital acute rehabilitation and referral to post-acute
      rehabilitation facilities among neurotrauma centres across Europe.

PMID- 28440842
TI  - ?

PMID- 28440843
TI  - ?

PMID- 28440844
TI  - ?

PMID- 28440845
TI  - ?

PMID- 28440846
TI  - ?
AB  - Energy restriction and adherence required for weight loss without surgery Non
      surgical weight loss treatment has not been shown to reduce mortality or
      cardiovascular morbidity, but can prevent diabetes mellitus and improves
      cardiovascular risk factors. For weight loss, energy restriction is fundamental
      and can lead to an average 2 to 20 kg loss over 6 to 12 months. Pharmacological
      treatment, behaviour therapy, physical activity and weight loss advice through
      web sites and smartphone applications and combinations in addition to energy
      restriction can contribute to further, but relatively limited weight loss up to
      30 months. Adherence to the treatment is necessary for both weight loss and long
      term weight loss maintenance.

PMID- 28440847
TI  - ?
AB  - Large bowel obstruction with effects on the mediastinum We present a patient in
      which the colon and left kidney herniated through a left-sided diaphragmatic
      hernia. The cause of the hernia was unknown, although most likely it emanated
      from an earlier diaphragmatic rupture caused by trauma. Due to a diverticular
      stenosis of the sigmoid colon, the patient developed large bowel obstruction,
      causing displacement of mediastinal structures. Emergency laparotomy and
      anterolateral thoracotomy was performed.

PMID- 28440848
TI  - [The number of suicides can be reduced - evidence exists].

PMID- 28440849
TI  - [Replace the quality registries with improvement networks].

PMID- 28440850
TI  - ?

PMID- 28440851
TI  - [Waste of resources counteracts individualized COPD treatment].

PMID- 28440852
TI  - [Warning against over-interpretation of the Swedish Agency for Health Technology
      Assessment and Assessment of Social Services conclusions about ketamine].

PMID- 28440853
TI  - Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with
      cystic fibrosis.
AB  - BACKGROUND: Respiratory tract infection with Pseudomonas aeruginosa occurs in
      most people with cystic fibrosis. Once chronic infection is established,
      Pseudomonas aeruginosa is virtually impossible to eradicate and is associated
      with increased mortality and morbidity. Early infection may be easier to
      eradicate.This is an update of a Cochrane review first published in 2003, and
      previously updated in 2006, 2009 and 2014. OBJECTIVES: To determine whether
      antibiotic treatment of early Pseudomonas aeruginosa infection in children and
      adults with cystic fibrosis eradicates the organism, delays the onset of chronic
      infection, and results in clinical improvement. To evaluate whether there is
      evidence that a particular antibiotic strategy is superior to or more cost
      effective than other strategies and to compare the adverse effects of different
      antibiotic strategies (including respiratory infection with other micro
      organisms). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders Group Trials Register comprising references identified from
      comprehensive electronic database searches and handsearches of relevant journals
      and abstract books of conference proceedings.Most recent search: 10 October 2016.
      SELECTION CRITERIA: We included randomised controlled trials of people with
      cystic fibrosis, in whom Pseudomonas aeruginosa had recently been isolated from
      respiratory secretions. We compared combinations of inhaled, oral or intravenous
      antibiotics with placebo, usual treatment or other combinations of inhaled, oral
      or intravenous antibiotics. We excluded non-randomised trials, cross-over trials,
      and those utilising historical controls. DATA COLLECTION AND ANALYSIS: Both
      authors independently selected trials, assessed risk of bias and extracted data.
      MAIN RESULTS: The search identified 60 trials; seven trials (744 participants)
      with a duration between 28 days and 27 months were eligible for inclusion. Three
      of the trials are over 10 years old and their results may be less applicable
      today given the changes in standard treatment. Some of the trials had low numbers
      of participants and most had relatively short follow-up periods; however, there
      was generally a low risk of bias from missing data. In most trials it was
      difficult to blind participants and clinicians to treatment given the
      interventions and comparators used. Two trials were supported by the
      manufacturers of the antibiotic used.Evidence from two trials (38 participants)
      at the two-month time-point showed treatment of early Pseudomonas aeruginosa
      infection with inhaled tobramycin results in microbiological eradication of the
      organism from respiratory secretions more often than placebo, odds ratio 0.15
      (95% confidence interval (CI) 0.03 to 0.65) and data from one of these trials,
      with longer follow up, suggested that this effect may persist for up to 12
      months.One randomised controlled trial (26 participants) compared oral
      ciprofloxacin and nebulised colistin versus usual treatment. Results after two
      years suggested treatment of early infection results in microbiological
      eradication of Pseudomonas aeruginosa more often than no anti-pseudomonal
      treatment, odds ratio 0.12 (95% CI 0.02 to 0.79).One trial comparing 28 days to
      56 days treatment with nebulised tobramycin solution for inhalation in 88
      participants showed that both treatments were effective and well-tolerated, with
      no notable additional improvement with longer over shorter duration of therapy.
      However, this trial was not powered to detect non-inferiority or equivalence .A
      trial of oral ciprofloxacin with inhaled colistin versus nebulised tobramycin
      solution for inhalation alone (223 participants) failed to show a difference
      between the two strategies, although it was underpowered to show this. A further
      trial of inhaled colistin with oral ciprofloxacin versus nebulised tobramycin
      solution for inhalation with oral ciprofloxacin also showed no superiority of the
      former, with increased isolation of Stenotrophomonas maltophilia in both groups.A
      recent, large trial in 306 children aged between one and 12 years compared cycled
      nebulised tobramycin solution for inhalation to culture-based therapy and also
      ciprofloxacin to placebo. The primary analysis showed no difference in time to
      pulmonary exacerbation or proportion of Pseudomonas aeruginosa positive cultures.
      An analysis performed in this review (not adjusted for age) showed fewer
      participants in the cycled therapy group with one or more isolates of Pseudomonas
      aeruginosa, odds ratio 0.51 (95% CI 0.31 to 0.28). Using GRADE, the quality of
      evidence for outcomes was downgraded to moderate to very low. Downgrading
      decisions for Pseudomonas aeruginosa eradication and lung function were based on
      applicability (participants mostly children) and limitations in study design,
      with imprecision an additional limitation for lung function, growth parameters
      and adverse effects. AUTHORS' CONCLUSIONS: We found that nebulised antibiotics,
      alone or in combination with oral antibiotics, were better than no treatment for
      early infection with Pseudomonas aeruginosa. Eradication may be sustained for up
      to two years. There is insufficient evidence to determine whether antibiotic
      strategies for the eradication of early Pseudomonas aeruginosa decrease mortality
      or morbidity, improve quality of life, or are associated with adverse effects
      compared to placebo or standard treatment. Four trials comparing two active
      treatments have failed to show differences in rates of eradication of Pseudomonas
      aeruginosa. There have been no published randomised controlled trials that
      investigate the efficacy of intravenous antibiotics to eradicate Pseudomonas
      aeruginosa in cystic fibrosis. Overall, there is still insufficient evidence from
      this review to state which antibiotic strategy should be used for the eradication
      of early Pseudomonas aeruginosa infection in cystic fibrosis.

PMID- 28440856
TI  - When a cesarean section scar is more than an innocent bystander in a subsequent
      pregnancy: Ultrasound to the rescue.
AB  - Over the years, cesarean section has played a pivotal role in reducing maternal
      and perinatal morbidity and mortality. With the rising trend of this surgery, a
      substantial number of pregnant women have a cesarean section scar. The scar can
      serve as the abode of grave conditions in subsequent pregnancies, namely cesarean
      scar pregnancy, morbidly adherent placenta, and scar dehiscence. Sonography has
      emerged as a robust tool for the diagnosis of these potentially life-threatening
      conditions. This review highlights the key sonographic features of various
      complications that can occur at the cesarean scar site in subsequent pregnancies.
      (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:319-327, 2017.

PMID- 28440855
TI  - Accuracy of Current Diagnostic Criteria for Acute Bacterial Infection in Older
      Adults in the Emergency Department.
AB  - OBJECTIVES: To compare the accuracy of the Loeb criteria, emergency department
      (ED) physicians' diagnoses, and Centers for Disease Control and Prevention (CDC)
      guidelines for acute bacterial infection in older adults with a criterion
      standard expert review. DESIGN: Prospective, observational study. SETTING: Urban,
      tertiary-care ED. PARTICIPANTS: Individuals aged 65 and older in the ED,
      excluding those who were incarcerated, underwent a trauma, did not speak English,
      or were unable to consent. MEASUREMENTS: Two physician experts identified
      bacterial infections using clinical judgement, participant surveys, and medical
      records; a third adjudicated in cases of disagreement. Agreement and test
      characteristics were measured for ED physician diagnosis, Loeb criteria, and CDC
      surveillance guidelines. RESULTS: Criterion-standard review identified bacterial
      infection in 77 of 424 participants (18%) (18 (4.2%) lower respiratory, 19 (4.5%)
      urinary tract (UTI), 22 (5.2%) gastrointestinal, 15 (3.5%) skin and soft tissue).
      ED physicians diagnosed infection in 71 (17%), but there were 33 with under- and
      27 with overdiagnosis. Physician agreement with the criterion standard was
      moderate for infection overall and each infection type (kappa = 0.48-0.59), but
      sensitivity was low (<67%), and the negative likelihood ratio (LR(-)) was greater
      than 0.30 for all infections. The Loeb criteria had poor sensitivity, agreement,
      and LR(-) for lower respiratory (50%, kappa = 0.55; 0.51) and urinary tract
      infection (26%, kappa = 0.34; 0.74), but 87% sensitivity (kappa = 0.78; LR(-)
      0.14) for skin and soft tissue infections. CDC guidelines had moderate agreement
      but poor sensitivity and LR(-). CONCLUSION: Emergency physicians often under- and
      overdiagnose infections in older adults. The Loeb criteria are useful only for
      diagnosing skin and soft tissue infections. CDC guidelines are inadequate in the
      ED. New criteria are needed to aid ED physicians in accurately diagnosing
      infection in older adults.

PMID- 28440857
TI  - The anterior complex: A visual mnemonic to aid in identification of normal
      structures.
AB  - The anterior complex of the fetal brain is a group of structures that are
      important to evaluate during the routine anatomic survey to exclude several
      serious brain malformations. These structures include the cavum septum
      pellucidum, anterior horns, interhemispheric fissure, callosal sulcus, and corpus
      callosum. The relationship between these structures is easily remembered with the
      presented visual cartoon. (c) 2017 Wiley Periodicals, Inc. J Clin Ultrasound
      45:477-479, 2017.

PMID- 28440854
TI  - Neuroprotective Diets Are Associated with Better Cognitive Function: The Health
      and Retirement Study.
AB  - OBJECTIVES: To evaluate the association between the Mediterranean diet (MedDiet)
      and the Mediterranean-DASH diet Intervention for Neurodegeneration Delay (MIND
      diet) and cognition in a nationally representative population of older U.S.
      adults. DESIGN: Population-based cross-sectional study. SETTING: Health and
      Retirement Study. PARTICIPANTS: Community-dwelling older adults (N = 5,907; mean
      age 67.8 +/- 10.8). MEASUREMENTS: Adherence to dietary patterns was determined
      from food frequency questionnaires using criteria determined a priori to generate
      diet scores for the MedDiet (range 0-55) and MIND diet (range 0-15). Cognitive
      performance was measured using a composite test score of global cognitive
      function (range 0-27). Linear regression was used to compare cognitive
      performance according to tertiles of dietary pattern. Logistic regression was
      used to examine the association between dietary patterns and clinically
      significant cognitive impairment. Models were adjusted for age, sex, race,
      educational attainment, and other health and lifestyle covariates. RESULTS:
      Participants with mid (odds ratio (OR) = 0.85, 95% confidence interval (CI) =
      0.71-1.02, P = .08) and high (OR 0.65, 95% CI = 0.52-0.81, P < .001) MedDiet
      scores were less likely to have poor cognitive performance than those with low
      scores in fully adjusted models. Results for the MIND diet were similar. Higher
      scores in each dietary pattern were independently associated with significantly
      better cognitive function (P < .001) in a dose-response manner (P trend  < .001).
      CONCLUSION: In a large nationally representative population of older adults,
      greater adherence to the MedDiet and MIND diet was independently associated with
      better cognitive function and lower risk of cognitive impairment. Clinical trials
      are required to elucidate the role of dietary patterns in cognitive aging.

PMID- 28440858
TI  - Treatment with disease-modifying drugs for people with a first clinical attack
      suggestive of multiple sclerosis.
AB  - BACKGROUND: The treatment of multiple sclerosis has changed over the last 20
      years. The advent of disease-modifying drugs in the mid-1990s heralded a period
      of rapid progress in the understanding and management of multiple sclerosis. With
      the support of magnetic resonance imaging early diagnosis is possible, enabling
      treatment initiation at the time of the first clinical attack. As most of the
      disease-modifying drugs are associated with adverse events, patients and
      clinicians need to weigh the benefit and safety of the various early treatment
      options before taking informed decisions. OBJECTIVES: 1. to estimate the benefit
      and safety of disease-modifying drugs that have been evaluated in all studies
      (randomised or non-randomised) for the treatment of a first clinical attack
      suggestive of MS compared either with placebo or no treatment;2. to assess the
      relative efficacy and safety of disease-modifying drugs according to their
      benefit and safety;3. to estimate the benefit and safety of disease-modifying
      drugs that have been evaluated in all studies (randomised or non-randomised) for
      treatment started after a first attack ('early treatment') compared with
      treatment started after a second attack or at another later time point ('delayed
      treatment'). SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare
      Diseases of the CNS Group Trials Register, MEDLINE, Embase, CINAHL, LILACS,
      clinicaltrials.gov, the WHO trials registry, and US Food and Drug Administration
      (FDA) reports, and searched for unpublished studies (until December 2016).
      SELECTION CRITERIA: We included randomised and observational studies that
      evaluated one or more drugs as monotherapy in adult participants with a first
      clinical attack suggestive of MS. We considered evidence on alemtuzumab,
      azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, glatiramer
      acetate, immunoglobulins, interferon beta-1b, interferon beta-1a (Rebif(r),
      Avonex(r)), laquinimod, mitoxantrone, natalizumab, ocrelizumab, pegylated
      interferon beta-1a, rituximab and teriflunomide. DATA COLLECTION AND ANALYSIS:
      Two teams of three authors each independently selected studies and extracted
      data. The primary outcomes were disability-worsening, relapses, occurrence of at
      least one serious adverse event (AE) and withdrawing from the study or
      discontinuing the drug because of AEs. Time to conversion to clinically definite
      MS (CDMS) defined by Poser diagnostic criteria, and probability to discontinue
      the treatment or dropout for any reason were recorded as secondary outcomes. We
      synthesized study data using random-effects meta-analyses and performed indirect
      comparisons between drugs. We calculated odds ratios (OR) and hazard ratios (HR)
      along with relative 95% confidence intervals (CI) for all outcomes. We estimated
      the absolute effects only for primary outcomes. We evaluated the credibility of
      the evidence using the GRADE system. MAIN RESULTS: We included 10 randomised
      trials, eight open-label extension studies (OLEs) and four cohort studies
      published between 2010 and 2016. The overall risk of bias was high and the
      reporting of AEs was scarce. The quality of the evidence associated with the
      results ranges from low to very low. Early treatment versus placebo during the
      first 24 months' follow-upThere was a small, non-significant advantage of early
      treatment compared with placebo in disability-worsening (6.4% fewer (13.9 fewer
      to 3 more) participants with disability-worsening with interferon beta-1a
      (Rebif(r)) or teriflunomide) and in relapses (10% fewer (20.3 fewer to 2.8 more)
      participants with relapses with teriflunomide). Early treatment was associated
      with 1.6% fewer participants with at least one serious AE (3 fewer to 0.2 more).
      Participants on early treatment were on average 4.6% times (0.3 fewer to 15.4
      more) more likely to withdraw from the study due to AEs. This result was mostly
      driven by studies on interferon beta 1-b, glatiramer acetate and cladribine that
      were associated with significantly more withdrawals for AEs. Early treatment
      decreased the hazard of conversion to CDMS (HR 0.53, 95% CI 0.47 to 0.60).
      Comparing active interventions during the first 24 months' follow-upIndirect
      comparison of interferon beta-1a (Rebif(r)) with teriflunomide did not show any
      difference on reducing disability-worsening (OR 0.84, 95% CI 0.43 to 1.66). We
      found no differences between the included drugs with respect to the hazard of
      conversion to CDMS. Interferon beta-1a (Rebif(r)) and teriflunomide were
      associated with fewer dropouts because of AEs compared with interferon beta-1b,
      cladribine and glatiramer acetate (ORs range between 0.03 and 0.29, with
      substantial uncertainty). Early versus delayed treatmentWe did not find evidence
      of differences between early and delayed treatments for disability-worsening at a
      maximum of five years' follow-up (3% fewer participants with early treatment (15
      fewer to 11.1 more)). There was important variability across interventions; early
      treatment with interferon beta-1b considerably reduced the odds of participants
      with disability-worsening during three and five years' follow-up (OR 0.52, 95% CI
      0.32 to 0.84 and OR 0.57, 95% CI 0.36 to 0.89). The early treatment group had
      19.6% fewer participants with relapses (26.7 fewer to 12.7 fewer) compared to
      late treatment at a maximum of five years' follow-up and early treatment
      decreased the hazard of conversion to CDMS at any follow-up up to 10 years (i.e.
      over five years' follow-up HR 0.62, 95% CI 0.53 to 0.73). We did not draw any
      conclusions on long-term serious AEs or discontinuation due to AEs because of
      inadequacies in the available data both in the included OLEs and cohort studies.
      AUTHORS' CONCLUSIONS: Very low-quality evidence suggests a small and uncertain
      benefit with early treatment compared with placebo in reducing disability
      worsening and relapses. The advantage of early treatment compared with delayed on
      disability-worsening was heterogeneous depending on the actual drug used and
      based on very low-quality evidence. Low-quality evidence suggests that the
      chances of relapse are less with early treatment compared with delayed. Early
      treatment reduced the hazard of conversion to CDMS compared either with placebo,
      no treatment or delayed treatment, both in short- and long-term follow-up. Low
      quality evidence suggests that early treatment is associated with fewer
      participants with at least one serious AE compared with placebo. Very low-quality
      evidence suggests that, compared with placebo, early treatment leads to more
      withdrawals or treatment discontinuation due to AEs. Difference between drugs on
      short-term benefit and safety was uncertain because few studies and only indirect
      comparisons were available. Long-term safety of early treatment is uncertain
      because of inadequately reported or unavailable data.

PMID- 28440859
TI  - Sonographic detection of a lingual node metastasis from early squamous cell
      cancer of the tongue.
AB  - Lingual node metastasis from early-stage squamous cell carcinoma of the tongue is
      uncommon and difficult to detect. We present a case of a lingual lymph node
      metastasis from an early tongue cancer. Sonography demonstrated a small
      nonpalpable lingual node on the floor of the mouth. The patient underwent
      complete surgical resection and had no evidence of recurrence 5 years later. (c)
      2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:69-72, 2018.

PMID- 28440860
TI  - Doppler ultrasonographic measurement of short-term effects of valsalva maneuver
      on retrobulbar blood flow.
AB  - BACKGROUND: To investigate the effects of Valsalva maneuver (VM) on retrobulbar
      blood flow parameters in healthy subjects. METHODS: Participants without any
      ophthalmologic or systemic pathology were examined in supine position with color
      and pulsed Doppler imaging for blood flow measurement, via a paraocular approach,
      in the ophthalmic artery (OA), central retinal artery (CRA), central retinal vein
      (CRV), nasal posterior ciliary artery (NPCA), and temporal posterior ciliary
      artery (TPCA), 10 seconds after a 35- to 40-mm Hg expiratory pressure was
      reached. Peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility
      index (PI), and resistivity index (RI) values were recorded for each artery. PSV
      and EDV values were recorded for CRV. RESULTS: There were significant differences
      between resting and VM values of PSV and EDV of CRA, RI of NPCA, and PI, RI, and
      EDV of TPCA. Resting CRA-EDV, CRV-PSV, and CRV-EDV were positively correlated
      whereas resting OA-PSV and CRA-PI, and OA-PSV, CRA-PSV, and CRA-EDV during VM,
      were negatively correlated with age. CONCLUSIONS: VM induces a short-term
      increase in CRA blood flow and a decrease in NPCA and TPCA RI. Additional studies
      with a longer Doppler recording during VM, in a larger population sample, are
      required to allow definitive interpretation. (c) 2017 Wiley Periodicals, Inc. J
      Clin Ultrasound 45:551-555, 2017.

PMID- 28440861
TI  - Findings from the Families on Track Intervention Pilot Trial for Children with
      Fetal Alcohol Spectrum Disorders and Their Families.
AB  - BACKGROUND: Individuals with fetal alcohol spectrum disorders (FASD) are at high
      risk for costly, debilitating mental health problems and secondary conditions,
      such as school disruption, trouble with the law, and substance use. The study
      objective was to pilot a multicomponent intervention designed to prevent
      secondary conditions in children with FASD and improve family adaptation.
      METHODS: Thirty children with FASD or prenatal alcohol exposure (PAE) (ages 4 to
      8) and their primary caregivers were enrolled. Families were randomized to either
      the Families on Track Integrated Preventive Intervention or an active control of
      neuropsychological assessment and personalized community referrals. The 30-week
      intervention integrates scientifically validated bimonthly, in-home parent
      behavioral consultation, and weekly child skills groups. Outcomes measured at
      baseline and follow-up postintervention included intervention satisfaction, child
      emotional and behavioral functioning, child self-esteem, caregiver knowledge of
      FASD and advocacy, caregiver attitudes, use of targeted parenting practices,
      perceived family needs met, social support, and self-care. Data analysis
      emphasized calculation of effect sizes and was supplemented with analysis of
      variance techniques. RESULTS: Analyses indicated that families participating in
      the intervention reported high program satisfaction. Relative to comparison group
      outcomes, the intervention was associated with medium-to-large effects for child
      emotion regulation, self-esteem, and anxiety. Medium-sized improvements in
      disruptive behavior were observed for both groups. Medium and large effects were
      seen for important caregiver outcomes: knowledge of FASD and advocacy,
      attributions of behavior, use of antecedent strategies, parenting efficacy,
      family needs met, social support, and self-care. CONCLUSIONS: This pilot study
      yielded promising findings from the multicomponent Families on Track Integrated
      Preventive Intervention for child and caregiver outcomes. An important next step
      is to complete a randomized control trial of the Families on Track Program with a
      larger sample fully representative of this underserved clinical population with
      built-in study of implementation parameters.

PMID- 28440862
TI  - A large intrauterine vascular lesion developing after the successful treatment of
      a cesarean scar pregnancy with methotrexate injection.
AB  - A cesarean scar pregnancy is a rare type of ectopic pregnancy. Induced abortion
      by local methotrexate (MTX) injection is an effective management approach. We
      describe a case in which a large intrauterine vascular lesion appeared after the
      sonographic-guided local injection of MTX, which successfully induced the
      abortion of the cesarean scar pregnancy. Although a cesarean scar pregnancy may
      be safely treated with a local MTX injection, close follow-up, including serum
      beta-human chorionic gonadotropin level measurement and Doppler sonography, is
      needed because an intrauterine vascular lesion could develop even after a
      successfully induced abortion. (c) 2017 Wiley Periodicals, Inc. J Clin Ultrasound
      46:222-226, 2018.

PMID- 28440863
TI  - Finger extension weakness and downbeat nystagmus motor neuron disease syndrome: A
      novel motor neuron disorder?
AB  - INTRODUCTION: Disturbances of eye movements are infrequently encountered in motor
      neuron diseases (MNDs) or motor neuropathies, and there is no known syndrome that
      combines progressive muscle weakness with downbeat nystagmus. METHODS: To
      describe the core clinical features of a syndrome of MND associated with downbeat
      nystagmus, clinical features were collected from 6 patients. RESULTS: All
      patients had slowly progressive muscle weakness and wasting in combination with
      downbeat nystagmus, which was clinically most obvious in downward and lateral
      gaze. Onset was in the second to fourth decade with finger extension weakness,
      progressing to other distal and sometimes more proximal muscles. Visual
      complaints were not always present. Electrodiagnostic testing showed signs of
      regional motor axonal loss in all patients. DISCUSSION: The etiology of this
      syndrome remains elusive. Because finger extension weakness and downbeat
      nystagmus are the discriminating clinical features of this MND, we propose the
      name FEWDON-MND syndrome. Muscle Nerve 56: 1164-1168, 2017.

PMID- 28440864
TI  - Breast cancer stage variation and survival in association with insurance status
      and sociodemographic factors in US women 18 to 64 years old.
AB  - BACKGROUND: Few population-based studies have examined the association between
      health insurance status and breast cancer stage at diagnosis and survival. The
      degree to which sociodemographic characteristics explain this association is also
      unclear. This study examined associations between insurance status and
      sociodemographic characteristics and stage at diagnosis and survival. METHODS:
      Using the Surveillance, Epidemiology, and End Results 18 registries database, we
      identified 52,048 women aged 18 to 64 years who were diagnosed with breast cancer
      in 2007 and 2008. Associations between insurance status and sociodemographic
      variables and stage at diagnosis and survival were examined with logistic and Cox
      proportional hazards regression models to calculate adjusted odds ratios (ORs),
      hazard ratios (HRs), and associated confidence intervals (CIs). RESULTS: The odds
      of a later stage breast cancer diagnosis were increased in women with Medicaid
      (OR, 2.36; 95% CI, 2.19-2.55) and no insurance (OR, 2.64; 95% CI, 2.29-3.04)
      versus private insurance, in women who had reported black race (OR, 1.18; 95% CI,
      1.09-1.28) versus white race, in women who were unmarried (OR, 1.25; 95% CI, 1.18
      1.33) versus married at diagnosis, and in women who were 18 to 39 years old (OR,
      1.29; 95% CI, 1.18-1.41) versus 40 to 64 years old at diagnosis. The hazard of
      breast cancer death was increased in association with Medicaid (HR, 1.40; 95% CI,
      1.30-1.51) and no insurance (HR, 1.61; 95% CI, 1.41-1.84) versus private
      insurance, with reported black race (HR, 1.39; 95% CI, 1.29-1.50) versus reported
      white race, and with being unmarried (HR, 1.19; 95% CI, 1.12-1.27) versus being
      married. CONCLUSIONS: Insurance status at diagnosis and sociodemographic factors
      are associated with breast cancer mortality. Factors underlying these
      associations warrant further study. Cancer 2017;123:3125-31. (c) 2017 American
      Cancer Society.

PMID- 28440865
TI  - Generation of wavy structure on lipid membrane by peripheral proteins: a linear
      elastic analysis.
AB  - We carry out a linear elastic analysis to study wavy structure generation on
      lipid membrane by peripheral membrane proteins. We model the lipid membrane as
      linearly elastic and anisotropic material. The hydrophobic insertion by proteins
      into the lipid membrane has been idealized as penetration of rigid rod-like
      inclusions into the membrane and the electrostatic interaction between protein
      and membrane has been modeled by a distributed surface traction acting on the
      membrane surface. With the proposed model we study curvature generation by
      several binding domains of peripheral membrane proteins containing BAR domains
      and amphipathic alpha-helices. It is observed that electrostatic interaction is
      essential for curvature generation by the BAR domains.

PMID- 28440866
TI  - A Prospective Comparison of How the Level of Response to Alcohol and Impulsivity
      Relate to Future DSM-IV Alcohol Problems in the COGA Youth Panel.
AB  - BACKGROUND: Alcohol problems reflect both environmental and genetic
      characteristics that often operate through endophenotypes like low levels of
      response (low LRs) to alcohol and higher impulsivity. Relationships of these
      preexisting characteristics to alcohol problems have been studied, but few
      analyses have included both low LR and impulsivity in the same model. METHODS: We
      extracted prospective data from 1,028 participants in the Prospective Youth
      Sample of the Collaborative Study on the Genetics of Alcoholism (COGA). At Time 1
      (age 18), these drinking but non-alcohol-dependent males and females completed
      the Barratt Impulsivity Scale and the Self-Report of the Effects of Alcohol
      questionnaire regarding drinks required for effects the first 5 times of drinking
      (SRE5-LR). Two years later, they reported perceived drinking patterns of peers
      (PEER), their own alcohol expectancies (EXPECT), and their drinking to cope with
      stress (COPE). Subsequently, at Time 3, participants reported numbers of up to 11
      DSM-IV alcohol criterion items experienced in the 2 years since Time 2 (ALC
      PROBS). Data were analyzed using structural equation modeling (SEM). RESULTS: In
      the SEM, Baseline SRE5-LR and impulsivity were weakly related and did not
      interact in predicting later ALC PROBS. LR was directly linked to Time 3 ALC
      PROBS and to PEER, but had no direct path to EXPECT, with partial mediation to
      ALC PROBS through PEER to EXPECT and via COPE. Impulsivity did not relate
      directly to ALC PROBS or PEER, but was directly related to EXPECT and COPE, with
      effects on ALC PROBS also operating through EXPECT and COPE. CONCLUSIONS: Low LRs
      and impulsivity related to Time 3 ALC PROBS through somewhat different paths.
      Education- and counseling-based approaches to mitigate future alcohol problems
      may benefit from emphasizing different potential mediators of adverse alcohol
      outcomes for youth with low LRs versus those with high impulsivity or both
      characteristics.

PMID- 28440867
TI  - The epileptology of Koolen-de Vries syndrome: Electro-clinico-radiologic findings
      in 31 patients.
AB  - OBJECTIVE: This study was designed to describe the spectrum of epilepsy
      phenotypes in Koolen-de Vries syndrome (KdVS), a genetic syndrome involving
      dysmorphic features, intellectual disability, hypotonia, and congenital
      malformations, that occurs secondary to 17q21.31 microdeletions and heterozygous
      mutations in KANSL1. METHODS: We were invited to attend a large gathering of
      individuals with KdVS and their families. While there, we recruited individuals
      with KdVS and seizures, and performed thorough phenotyping. Additional subjects
      were included who approached us after the family support group brought attention
      to our research via social media. Inclusion criteria were genetic testing results
      demonstrating 17q21.31 deletion or KANSL1 mutation, and at least one seizure.
      RESULTS: Thirty-one individuals were studied, aged 2-35 years. Median age at
      seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after
      onset. Focal impaired awareness seizures were the most frequent seizure type
      occurring in 20 of 31, usually with prominent autonomic features. Twenty-one
      patients had prolonged seizures and, at times, refractory status epilepticus.
      Electroencephalography (EEG) showed focal/multifocal epileptiform discharges in
      20 of 26. MRI studies of 13 patients were reviewed, and all had structural
      anomalies. Corpus callosum dysgenesis, abnormal hippocampi, and dilated
      ventricles were the most common, although periventricular nodular heterotopia,
      focal cortical dysplasia, abnormal sulcation, and brainstem and cerebellum
      abnormalities were also observed. One patient underwent epilepsy surgery for a
      lesion that proved to be an angiocentric glioma. SIGNIFICANCE: The typical
      epilepsy phenotype of KdVS involves childhood-onset focal seizures that are
      prolonged and have prominent autonomic features. Multifocal epileptiform
      discharges are the typical EEG pattern. Structural brain abnormalities may be
      universal, including signs of abnormal neuroblast migration and abnormal axonal
      guidance. Epilepsy surgery should be undertaken with care given the widespread
      neuroanatomic abnormalities; however, tumors are a rare, yet important,
      occurrence.

PMID- 28440868
TI  - Improved outcomes after successful implementation of a pediatric early warning
      system (PEWS) in a resource-limited pediatric oncology hospital.
AB  - BACKGROUND: Hospitalized pediatric oncology patients are at high risk of clinical
      decline and mortality, particularly in resource-limited settings. Pediatric early
      warning systems (PEWS) aid in the early identification of clinical deterioration;
      however, there are limited data regarding their feasibility or impact in low
      resource settings. This study describes the successful implementation of PEWS at
      the Unidad Nacional de Oncologia Pediatrica (UNOP), a pediatric oncology hospital
      in Guatemala, resulting in improved inpatient outcomes. METHODS: A modified PEWS
      was implemented at UNOP with systems to track errors, transfers to a higher level
      of care, and high scores. A retrospective cohort study was used to evaluate
      clinical deterioration events in the year before and after PEWS implementation.
      RESULTS: After PEWS implementation at UNOP, there was 100% compliance with PEWS
      documentation and an error rate of <10%. Implementation resulted in 5 high PEWS
      per week, with 30% of patients transferring to a higher level of care. Among
      patients requiring transfer to the pediatric intensive care unit (PICU), 93% had
      an abnormal PEWS before transfer. The rate of clinical deterioration events
      decreased after PEWS implementation (9.3 vs 6.5 per 1000-hospitalpatient-days, p
      = .003). Despite an 18% increase in total hospital patient-days, PICU utilization
      for inpatient transfers decreased from 1376 to 1088 PICU patient-days per year
      (21% decrease; P<.001). CONCLUSIONS: This study describes the successful
      implementation of PEWS in a pediatric oncology hospital in Guatemala, resulting
      in decreased inpatient clinical deterioration events and PICU utilization. This
      work demonstrates that PEWS is a feasible and effective quality improvement
      measure to improve hospital care for children with cancer in hospitals with
      limited resources. Cancer 2017;123:2965-74. (c) 2017 American Cancer Society.

PMID- 28440869
TI  - Massive pleural effusion on the contralateral side of a venous peripherally
      inserted central catheter.
AB  - A preterm newborn infant, delivered at 30 weeks of gestation and 965 g birth
      weight, developed respiratory distress with resistant hypoxia after a central
      catheter line was inserted via the right venae brachialis on postnatal day 21.
      Left-sided massive pleural effusion, collapsed left lung with air bronchograms,
      and bidirectional shunting through reopened ductus arteriosus were detected by
      targeted neonatal echocardiography. Hydrothorax was drained under sonographic
      guidance, producing a milky-white fluid biochemically compatible with parenteral
      nutrition. We report this case of hydrothorax secondary to a misplaced central
      catheter on the contralateral side of its peripheral insertion. (c) 2017 Wiley
      Periodicals, Inc. J Clin Ultrasound 46:140-144, 2018.

PMID- 28440870
TI  - Intensity of male-male competition predicts morph diversity in a color
      polymorphic lizard.
AB  - Sexual selection is one of the main processes involved in the emergence and
      maintenance of heritable color polymorphisms in a variety of taxa. Here, we test
      whether the intensity of sexual selection, estimated from population sex ratio,
      predicts morph diversity in Podarcis muralis, a color polymorphic lizard with
      discrete white, yellow, orange, white-orange, and yellow-orange male and female
      phenotypes (i.e., morphs). In a sample of 116 Pyrenean populations and 5421
      lizards, sex ratios (m/f) vary from 0.29 to 2.5, with the number of morphs for
      each sex ranging from 2 to 5. Male-biased sex ratios are associated with
      increased morph diversity as measured with Shannon's diversity index. The main
      factor accounting for this relationship is male morph richness (i.e., the number
      of morphs). In contrast, female morph diversity is not related to sex ratio.
      These results suggest a relationship between the intensity of male intrasexual
      competition and male morph diversity. While other selective forces may interact
      with sexual selection in maintaining the color polymorphisms in P. muralis, this
      evidence suggests a complex evolutionary scenario possibly involving frequency
      dependent selection of alternative reproductive tactics and/or complex balancing
      selection.

PMID- 28440871
TI  - Effects of Different Salt Treatments on the Fermentation Metabolites and
      Bacterial Profiles of Kimchi.
AB  - The effects of purified salt (PS) and mineral-rich sea salt (MRS), both with
      different mineral profiles, on kimchi fermentation were studied using a culture
      dependent 16S rRNA sequencing technique and mass-based metabolomic analysis. The
      different mineral profiles in the fermentation medium caused changes in the
      bacterial profiles of the 2 kimchi products. An increase of Leuconostoc species
      in MRS-kimchi decreased the Lactobacillus/Leuconostoc ratio, which led to changes
      in metabolites (including sugars, amino acids, organic acids, lipids, sulfur
      compounds, and terpenoids) associated with kimchi quality. Although further
      studies on the relationship between these salt types and kimchi fermentation are
      needed, these results suggested that the MRS treatment had positively affected
      the changes of the kimchi mineral contents, bacterial growth, and metabolite
      profiles, which are linked to kimchi quality.

PMID- 28440873
TI  - Flashbulb memories of the Paris attacks.
AB  - Flashbulb memories are vivid autobiographical memories of the circumstances where
      an individual first learns about emotionally significant public events. Our paper
      assesses whether these memories were triggered by the attacks of Friday 13
      November 2015 in Paris. Two hundred and ninety-one participants answered a web
      based questionnaire that assessed their memory of the circumstances in which they
      first learned of the attacks. The questionnaire also assessed vividness,
      rehearsal, emotion, surprise and novelty. The results showed substantial and
      vivid recall of the context in which the participants first learned of the event.
      This recall was associated with fair rehearsal, negative emotional valence,
      surprise, and novelty. Regression analysis showed that the flashbulb recall was
      predicted by negative emotion. Negative emotion seems to play a key role in the
      formation of flashbulb memories, at least those associated with the Paris
      attacks.

PMID- 28440872
TI  - Lay health educators and print materials for the promotion of colorectal cancer
      screening among Korean Americans: A randomized comparative effectiveness study.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second most commonly diagnosed cancer
      among Korean American men and women. Although CRC screening is effective in
      reducing the burden of this disease, studies have shown that Korean Americans
      have low screening rates. METHODS: The authors conducted a 2-arm cluster
      randomized controlled trial comparing a brochure (print) with a brochure and lay
      health educator (LHE) outreach (print + LHE) in increasing CRC screening rates
      among Korean American individuals. Self-administered written surveys at baseline
      and at 6 months assessed knowledge of CRC and its screening, ever screening, and
      being up to date with screening. RESULTS: A total of 28 LHEs recruited 348
      participants aged 50 to 75 years from their social networks. Significant
      percentages of participants reported not having health insurance (29.3%) or a
      usual source of care (35.6%). At 6 months postintervention, the print + LHE
      participants had a greater increase in knowledge compared with those in the print
      arm (P = .0013). In multivariable analyses, both groups had significant increases
      in ever screening (print plus LHE: odds ratio [OR], 1.60 [95% confidence interval
      (95% CI), 1.26-2.03] and print: OR, 1.42 [95% CI, 1.10-1.82]) and being up to
      date with screening (print plus LHE: OR, 1.63 [95% CI, 1.23-2.16] and print: OR,
      1.40 [95% CI, 1.04-1.89]). However, these increases did not differ significantly
      between the study arms. Having insurance and having seen a provider within the
      past year were found to be positively associated with screening. CONCLUSIONS:
      Compared with a brochure, LHE outreach yielded greater increases in knowledge but
      resulted in similar increases in CRC screening in a Korean American population
      with barriers to health care access. More work is needed to appropriately address
      logistical and system barriers in this community. Cancer 2017;123:2705-15. (c)
      2017 American Cancer Society.

PMID- 28440874
TI  - Role of glycogen synthase kinase 3 in ischemia-induced blood-brain barrier
      disruption in aged female rats.
AB  - Estrogen receptors have protective effects against ischemic brain injury.
      However, the molecular mechanisms underlying this phenomenon have yet to be well
      studied. Given that inhibition of glycogen synthase kinase (GSK3) can reduce
      cerebral ischemia/reperfusion injury, we hypothesized that estrogen receptors
      mediated protective effects against ischemia-induced blood-brain barrier (BBB)
      disruption involve inhibition of GSK3. Thus, we evaluated GSK3 expression in the
      brain of ovariectomized female rats, and examined the effects of
      intracerebroventricular pre-treatments of SB216763, GSK3 inhibitor, on BBB
      permeability following middle cerebral artery occlusion (MCAO). We also examined
      the role of specific estrogen receptor subtype in regulation of GSK3 expression
      and BBB permeability after MCAO. We found that ovariectomized female rats
      exhibited increased mRNA levels of estrogen receptor alpha (ERalpha) and estrogen
      receptor beta (ERbeta), and increased protein levels of GSK3beta but not
      GSK3alpha in brain cortical areas. Furthermore, intracerebroventricular pre
      treatments of SB216763 dose-dependently attenuated brain infarction volume, brain
      water contents, neurological deficits, and BBB disruption, and increased tight
      junction protein ZO-1 and occludin expression at 24 h following MCAO. Finally,
      activation of ERbeta but not ERalpha dose-dependently decreased GSK3beta
      expression at 24 h following MCAO. This was associated with increased tight
      junction protein expression and improved neurological scores. Thus, our study
      suggested that activation of ERbeta may protect against brain ischemia-induced
      BBB disruption by inhibiting GSK3beta-mediated signaling.

PMID- 28440875
TI  - Skin manifestations among GATA2-deficient patients.
AB  - GATA2 mutations have been identified in various diseases, such as MonoMAC
      syndrome, Emberger syndrome, familial myelodysplastic syndrome, acute myeloid
      leukaemia and dendritic cell, monocyte, B-cell and natural killer-cell
      deficiency. These syndromes present a wide range of clinical features, dominated
      by severe infections and haematological disorders such as myelodysplastic
      syndrome. Up to 70% of patients with GATA2 mutations have dermatological
      features, mainly genital or extragenital warts, panniculitis or erythema nodosum
      and lymphoedema. We report three patients presenting with common dermatological
      and haematological features leading to the diagnosis of GATA2 deficiency, but
      also with skin manifestations that have not been previously described: gingival
      hypertrophy, macroglossitis and glossitis and granulomatous lupoid facial
      lesions. Dermatologists can encounter patients with GATA2 mutations and should
      recognize this disorder.

PMID- 28440876
TI  - Triple-modality treatment in patients with advanced stage tonsil cancer.
AB  - BACKGROUND: Concurrent chemoradiation (CCRT) and upfront surgery followed by
      adjuvant therapy both are recommended treatment options for patients with
      advanced stage squamous cell carcinoma (SCC) of the tonsil. To the authors'
      knowledge, the question of whether surgical-based treatments can achieve better
      survival compared with CCRT has never been compared in a clinical trial. The
      authors analyzed the National Cancer Data Base to measure the impact of different
      treatment modalities on overall survival (OS). METHODS: All patients aged <=70
      years diagnosed with clinical stage III to IVB (excluding T4B) SCC of the tonsil
      from 1998 through 2011 were selected. Analysis was limited to patients receiving
      CCRT, surgery plus CCRT, or surgery followed by adjuvant radiotherapy (RT). OS
      was compared using the Kaplan-Meier method and log-rank test. Univariable and
      multivariable hazards analyses were performed to identify factors significant for
      survival. Propensity score matching was performed. RESULTS: There were 16,891
      patients who met the inclusion criteria. The most common treatment was CCRT (8123
      patients; 48.1%), followed by surgery plus CCRT (5249; 31.1%) and surgery plus RT
      (3519 patients; 20.8%). Patients treated with surgery plus CCRT were found to
      have the highest 3-year OS rate (88.5%) followed by those treated with surgery
      plus RT (84%) and CCRT (74.2%) (P<.0001). In a propensity score-matched
      subpopulation of 4962 patients, the 3-year OS rate was 90.2% for those treated
      with surgery plus CCRT, 84.9% for those treated with surgery plus RT, and 82.1%
      for those treated with definitive CCRT (P<.0001). CONCLUSIONS: Patients with
      advanced stage SCC of the tonsil who underwent surgery followed by CCRT had the
      greatest OS. Patients undergoing upfront surgery may avoid chemotherapy without
      jeopardizing survival. Triple-modality therapy may provide a survival benefit for
      a subset of patients with advanced stage tonsil cancer. Cancer 2017;123:3269-76.
      (c) 2017 American Cancer Society.

PMID- 28440877
TI  - Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment
      location and affect neuronal excitability in cultured hippocampal neurons.
AB  - Plasticity of the axon initial segment (AIS) has aroused great interest in recent
      years because it regulates action potential initiation and neuronal excitability.
      AIS plasticity manifests as modulation of ion channels or variation in AIS
      structure. However, the mechanisms underlying structural plasticity of the AIS
      are not well understood. Here, we combined immunofluorescence, patch-clamp
      recordings, and pharmacological methods in cultured hippocampal neurons to
      investigate the factors participating in AIS structural plasticity during
      development. With lowered neuronal density, the distance between the AIS and the
      soma increased, while neuronal excitability decreased, as shown by the increased
      action potential threshold and current threshold for firing an action potential.
      This variation in the location of the AIS was associated with cellular secretory
      substances, including brain-derived neurotrophic factor (BDNF) and neurotrophin 3
      (NT3). Indeed, blocking BDNF and NT3 with TrkB-Fc eliminated the effect of
      conditioned medium collected from high-density cultures on AIS relocation.
      Elevating the extracellular concentration of BDNF or NT3 promoted movement of the
      AIS proximally to the soma and increased neuronal excitability. Furthermore,
      knockdown of neurotrophin receptors TrkB and TrkC caused distal movement of the
      AIS. Our results demonstrate that BDNF and NT3 regulate AIS location and neuronal
      excitability. These regulatory functions of neurotrophic factors provide insight
      into the molecular mechanisms underlying AIS biology.

PMID- 28440878
TI  - An alert to Latin America: Current human papillomavirus vaccination trends
      highlight key barriers to successful implementation.

PMID- 28440879
TI  - Tick-borne encephalitis in patients vaccinated against this disease.
AB  - BACKGROUND: Information on tick-borne encephalitis (TBE) in patients already
      vaccinated against the disease is limited. OBJECTIVES: To compare the course and
      outcome in patients with vaccination breakthrough TBE with findings in patients
      who developed TBE without previous vaccination. METHODS: All adult patients
      diagnosed with TBE at a single medical centre during a 16-year period and who had
      received at least two doses of TBE vaccine before the onset of illness qualified
      for the study. For each patient with breakthrough TBE, two unvaccinated sex- and
      age-matched patients, diagnosed with TBE in the same year, were included for
      comparison. RESULTS: Amongst 2332 patients diagnosed with TBE in the period 2000
      2015, 39 (1.7%) had been vaccinated against the disease. Their median age was 59
      (20-83) years; 22 of 39 (56.4%) were male. In comparison with unvaccinated
      patients with TBE, those with breakthrough disease more often experienced a
      monophasic course of illness (P = 0.006), had a higher CSF leucocyte count (P =
      0.005), more often had urine retention (P = 0.012), more often needed ICU
      treatment (P = 0.009), were hospitalized for longer (P = 0.002) and had more
      severe acute illness (P = 0.004 for simple clinical assessment, P = 0.001 for
      severity score). CONCLUSION: In addition to several findings corroborating
      previous results in patients with vaccination breakthrough TBE, such as older age
      and the presence of a particular specific serum antibody pattern indicating
      anamnestic response, findings in this study indicate that the acute illness in
      patients with breakthrough TBE is more severe than in unvaccinated sex- and age
      matched patients who develop the disease.

PMID- 28440880
TI  - "To-be-forgotten" statements become less true: Memory processes involved in
      selection and forgetting lead to truthfulness changes of ambiguous sentences.
AB  - What happens when people try to forget something? What are the consequences of
      instructing people to intentionally forget a sentence? Recent studies employing
      the item-method directed forgetting paradigm have shown that to-be-forgotten
      (TBF) items are, in a subsequent task, emotionally devaluated relative to to-be
      remembered (TBR) items, an aftereffect of memory selection (Vivas, Marful,
      Panagiotidou & Bajo, 2016). As such, distractor devaluation by attentional
      selection generalizes to memory selection. In this study, we use the item-method
      directed forgetting paradigm to test the effects of memory selection and
      inhibition on truth judgments of ambiguous sentences. We expected the relative
      standing of an item in the task (i.e., whether it was instructed to be remembered
      or forgotten) to affect the truthfulness value of that item, making TBF items
      less valid/truthful than TBR items. As predicted, ambiguous sentences associated
      with a "Forget" cue were subsequently judged as less true than sentences
      associated with a "Remember" cue, suggesting that instructions to intentionally
      forget a statement can produce changes in the validity/truthfulness of that
      statement. To our knowledge, this is the first study to show an influence of
      memory processes involved in selection and forgetting on the perceived
      truthfulness of sentences.

PMID- 28440881
TI  - Overexpression of a type-I isopentenyl pyrophosphate isomerase of Artemisia annua
      in the cytosol leads to high arteannuin B production and artemisinin increase.
AB  - We recently characterized a gene-terpene network that is associated with
      artemisinin biosynthesis in self-pollinated (SP) Artemisia annua, an effective
      antimalarial plant. We hypothesize that an alteration of gene expression in the
      network may improve the production of artemisinin and its precursors. In this
      study, we cloned an isopentenyl pyrophosphate isomerase (IPPI) cDNA, AaIPPI1,
      from Artemisia annua (Aa). The full-length cDNA encodes a type-I IPPI containing
      a plastid transit peptide (PTP) at its amino terminus. After the removal of the
      PTP, the recombinant truncated AaIPPI1 isomerized isopentenyl pyrophosphate (IPP)
      to dimethyl allyl pyrophosphate (DMAPP) and vice versa. The steady-state
      equilibrium ratio of IPP/DMAPP in the enzymatic reactions was approximately 1:7.
      The truncated AaIPPI1 was overexpressed in the cytosol of the SP A. annua
      variety. The leaves of transgenic plants produced approximately 4% arteannuin B
      (g g-1 , dry weight, dw) and 0.17-0.25% artemisinin (g g-1 , dw), the levels of
      which were significantly higher than those in the leaves of wild-type plants. In
      addition, transgenic plants showed an increase in artemisinic acid production of
      more than 1% (g g-1 , dw). In contrast, isoprene formation was significantly
      reduced in transgenic plants. These results provide evidence that overexpression
      of AaIPPI1 in the cytosol can lead to metabolic alterations of terpenoid
      biosynthesis, and show that these transgenic plants have the potential to yield
      high production levels of arteannuin B as a new precursor source for artemisinin.

PMID- 28440882
TI  - Highly Selective Olefin-Assisted PdII -Catalyzed Oxidative Alkynylation of
      Enallenes.
AB  - An olefin-assisted, palladium-catalyzed oxidative alkynylation of enallenes for
      regio- and stereoselective synthesis of substituted trienynes has been developed.
      The reaction shows a broad substrate scope and good tolerance for various
      functional groups on the allene moiety, including carboxylic acid esters, free
      hydroxyls, imides, and alkyl groups. Also, a wide range of terminal alkynes with
      electron-donating and electron-withdrawing aryls, heteroaryls, alkyls,
      trimethylsilyl, and free hydroxyl groups are tolerated.

PMID- 28440883
TI  - A misunderstanding. Response to Dr Bilo et al.

PMID- 28440884
TI  - Radical Arylation of Anilines and Pyrroles via Aryldiazotates.
AB  - The radical arylation of anilines and pyrroles can be achieved under transition
      metal- and catalyst-free conditions by using aryldiazotates in strongly alkaline
      aqueous solutions. The aryldiazotates act as protected diazonium ions, which do
      not undergo azo coupling with electron-rich aromatic substrates, but can still
      serve as an aryl radical source at slightly elevated temperatures. Based on an
      improved preparation of aryldiazotates in aqueous solution, homolytic aromatic
      substitutions of anilines and pyrroles were conducted with good overall yields
      and high regioselectivity. Moreover, DFT calculations provided further
      mechanistic insights.

PMID- 28440885
TI  - Comparison of direct sequencing and Invader assay for Y93H mutation and response
      to interferon-free therapy in hepatitis C virus genotype 1b.
AB  - BACKGROUND AND AIM: Virologic failure of interferon-free therapy has been
      associated with Y93H mutation in the non-structure 5A region in hepatitis C virus
      (HCV) genotype 1b, and screening is recommended. A simple assay based on Q
      Invader technology was developed for Y93H mutant screening to reduce cost and
      effort. The present study sought to compare two methods of detection of Y93H
      mutation and to evaluate the effect of Y93H mutation on response to interferon
      free therapy. METHODS: Y93H mutation was examined in 258 patients with HCV
      genotype 1b using both direct sequencing analysis and the polymerase chain
      reaction (PCR)-Invader assay. Daclatasvir and asunaprevir or ledipasvir and
      sofosbuvir therapy was administered to 205 patients whose sustained virological
      responses (SVR) were checked. RESULTS: Hepatitis C virus was detected in 232 of
      258 patients by direct sequencing and in 236 of 258 patients by the PCR-Invader
      assay. Forty of 231 cases were defined as Y93 mutation by direct sequencing, and
      46 of 236 cases were defined as Y93 mutation by the PCR-Invader assay. SVR of
      patients who were Y93H by direct sequencing, Y93H by the PCR-Invader assay, and
      Y93H by both methods was 62.5%, 82.4%, and 50%, respectively. CONCLUSIONS: The
      sensitivity of the PCR-Invader assay was similar to that of direct sequencing
      analysis; however, the PCR-Invader assay had a better ability to detect minor
      strains. Combination of the two assays would improve prediction of the response
      to daclatasvir and asunaprevir, but Y93H mutation had little effect on SVR in
      ledipasvir and sofosbuvir therapy.

PMID- 28440886
TI  - Earthworm dispersal assay for rapidly evaluating soil quality.
AB  - Earthworms enhance soil functioning and are therefore key species in the soil.
      Their presence is generally a positive sign for a terrestrial ecosystem, because
      these species serve as important biomarkers in soil quality evaluations. We
      describe a novel bioassay, the "dispersal assay," that is a simple and rapid
      technique for field-based soil quality evaluations. It is based on the premise
      that earthworms prefer optimal soils if given the choice. Thus, assay tubes
      containing a reference soil were inserted in target sites, and earthworms were
      placed into these tubes. According to their soil preference, the earthworms
      dispersed into the surrounding soil, remained in the initial soil within the
      tubes, avoided both by crawling up the tube, or died. Furthermore, sensitivity
      responses to metal concentrations, electrical conductivity, and soil pH were
      observed in field tests. Although the dispersal assay did not completely match
      traditional toxicity endpoints such as earthworm survival, we found that it can
      serve as an in situ screening test for assessing soil quality. Overall, our
      dispersal assay was relatively rapid (within 24 h), had low levels of variation,
      and showed high correlations between earthworm behavior and soil physicochemical
      properties. Environ Toxicol Chem 2017;36:2766-2772. (c) 2017 SETAC.

PMID- 28440887
TI  - MicroRNA regulation of extracellular matrix components in the process of
      atherosclerotic plaque destabilization.
AB  - The process of atherosclerotic plaque destabilization, leading to myocardial
      infarction, is still not fully understood. The pathway - composed of structural
      and regulatory proteins of the extracellular matrix (ECM) such as collagen,
      elastin, small leucine-rich proteoglycans, metalloproteinases, cathepsins and
      serine proteases - is one potential way of atherosclerotic plaque
      destabilization. The expression of these proteins is controlled by different
      microRNA molecules. The goal of this paper is to summarize the current
      investigations and knowledge about ECM in the process of atherosclerotic plaque
      destabilization, giving special attention to epigenetic expression regulation by
      microRNA.

PMID- 28440888
TI  - Training dual tasks together or apart in Parkinson's disease: Results from the
      DUALITY trial.
AB  - BACKGROUND AND OBJECTIVES: Many controversies surround the usefulness of dual
      task training in Parkinson's disease (PD). This study (1) compared the efficacy
      of two different dual-task training programs for improving dual-task gait and (2)
      assessed the possible fall risk of such training. METHODS: Patients (N = 121)
      with a diagnosis of PD (aged 65.93 [+/-9.22] years, Hoehn and Yahr stage II-III
      on-medication) were randomized to (1) a consecutive group in which gait and
      cognitive tasks were trained separately or (2) an integrated group in which gait
      and cognitive tasks were trained simultaneously. Both interventions involved 6
      weeks of at-home physiotherapist-led training. Two baseline tests were performed
      as a 6-week control period before training. Posttests were performed immediately
      after training and at 12-week follow-up. Dual-task gait was assessed during
      trained and untrained secondary tasks to assess consolidation of learning. Fall
      risk was determined by a weekly telephone call for 24 weeks. RESULTS: No
      significant time by group interactions were found, suggesting that both training
      modes had a similar effect on dual-task gait. Immediately after training, and not
      after the control period, significant improvements (P < .001) in dual-task gait
      velocity were found in all trained and untrained dual tasks. Improvements ranged
      between 7.75% and 13.44% when compared with baseline values and were retained at
      12-week follow-up. No significant change in fall risk occurred in both study arms
      (P = .84). CONCLUSIONS: Consecutive and integrated dual-task training led to
      similar and sustained improvements in dual-task gait velocity without increasing
      fall risk. These novel findings support adoption of dual-task training in
      clinical practice. (c) 2017 International Parkinson and Movement Disorder
      Society.

PMID- 28440889
TI  - Glucagon-like peptide-1 analog, liraglutide, improves visceral sensation and gut
      permeability in rats.
AB  - BACKGROUND AND AIM: A glucagon-like peptide-1 analog, liraglutide, has been
      reported to block inflammatory somatic pain. We hypothesized that liraglutide
      attenuates lipopolysaccharide (LPS)-induced and repeated water avoidance stress
      (WAS)-induced visceral hypersensitivity and tested the hypothesis in rats.
      METHODS: The threshold of the visceromotor response induced by colonic balloon
      distention was measured to assess visceral sensation. Colonic permeability was
      determined in vivo by quantifying the absorbed Evans blue spectrophotometrically,
      which was instilled in the proximal colon for 15 min. The interleukin-6 level in
      colonic mucosa was also quantified using ELISA. RESULTS: Subcutaneously injected
      LPS (1 mg/kg) reduced the visceromotor response threshold after 3 h. Liraglutide
      (300 MUg/kg subcutaneously) at 15 h and 30 min before injecting LPS eliminated
      LPS-induced allodynia. It also blocked the allodynia induced by repeated water
      avoidance stress for 1 h for three consecutive days. Neither vagotomy nor
      naloxone altered the antinociceptive effect of liraglutide, but NG -nitro-L
      arginine methyl ester, a nitric oxide synthesis inhibitor, blocked it. LPS
      increased colonic permeability and the interleukin-6 level, and the analog
      significantly inhibited these responses. CONCLUSIONS: This study suggests that
      liraglutide blocked LPS-induced visceral allodynia, which may be a nitric oxide
      dependent response, and was probably mediated by inhibiting pro-inflammatory
      cytokine production and attenuating the increased gut permeability. Because the
      LPS-cytokine system is considered to contribute to altered visceral sensation in
      irritable bowel syndrome, these results indicate the possibility that liraglutide
      can be useful for treating this disease.

PMID- 28440891
TI  - Evaluation of three different decontamination techniques on biofilm formation,
      and on physical and chemical properties of resin composites.
AB  - OBJECTIVES: This study evaluated three different sterilization/disinfection
      techniques for resin composites on bacterial growth and surface modification
      after decontamination. METHODS: Two resin composites were sterilized/disinfected
      with three different techniques: UV light, 1% chloramine T, and 70% ethanol. Four
      different times were used for each technique to determine the shortest time that
      the solution or UV light was effective. The influence of
      sterilization/disinfection technique on bacterial growth was evaluated by
      analyzing the metabolic activity, using the AlamarBlueTM assay, bacterial
      viability, and SEM images from biofilms of Streptococcus mutans. The surface
      change, after the process, was analyzed with ATR/FTIR and SEM images. The
      solutions used for decontamination (1% chloramine-T and 70% ethanol) were
      analyzed with 1 H-NMR to identify any resin compounds leached during the process.
      RESULTS: One minute of decontamination was efficient for all three methods
      tested. Chloramine-T increased the surface porosity on resin composites, no
      changes were observed for UV light and 70% ethanol, however, 1 H-NMR identified
      leached monomers only when 70% ethanol was used. No chemical change of the
      materials was found under ATR/FTIR analyses after the decontamination process.
      Chloramine-T, with no previous wash, increased the bacterial viability for both
      resin composites and increased the bacterial metabolism for the resin composite
      without fluoride. CONCLUSION: UV light had no interference on the resin
      composites properties tested using 1 min of exposure compared to the other
      decontamination methods. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part
      B: Appl Biomater, 106B: 945-953, 2018.

PMID- 28440890
TI  - Fluorescence and autoradiographic evaluation of tau PET ligand PBB3 to alpha
      synuclein pathology.
AB  - BACKGROUND: The tau PET ligand 2-((1E,3E)-4-(6-([11 C]methylamino)pyridin-3
      yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ([11 C]PBB3) binds to a wide range of tau
      pathology; however, binding property of PBB3 to non-tau inclusions remains
      unknown. To clarify whether [11 C]PBB3 binds to alpha-synuclein pathology,
      reactivity of PBB3 was assessed by in vitro fluorescence and autoradiographic
      labeling of brain sections from alpha-synucleinopathies patients. METHOD: Of 10
      pure Lewy body disease and 120 multiple system atrophy (MSA) cases in the Mayo
      Clinic brain bank, we selected 3 Lewy body disease and 4 MSA cases with a range
      of alpha-synuclein severity based on the quantitative analysis of alpha-synuclein
      burden. PBB3 fluorescence labeling, double or single immunostaining for alpha
      synuclein and phospho-tau, Prussian blue staining, and in vitro autoradiography
      with [11 C]PBB3 were performed for these selected samples. RESULTS: PBB3
      fluorescence labeled various alpha-synuclein lesions including Lewy bodies, Lewy
      neurites, spheroids, glial cytoplasmic inclusions, and neuronal cytoplasmic
      inclusions. Meanwhile, autoradiographic labeling with [11 C]PBB3 at 10 nM
      demonstrated no significant binding in Lewy body disease cases. In contrast,
      significant autoradiographic binding of [11 C]PBB3 to the striatopallidal fibers
      was found in 2 MSA cases, which had high densities of glial cytoplasmic
      inclusions without tau or iron deposits in this region. CONCLUSIONS: Given that
      the maximum concentration of [11 C]PBB3 in human PET scans is approximately 10
      nM, the present data imply that alpha-synuclein pathology in Lewy body disease is
      undetectable by [11 C]PBB3-PET, whereas those in a subset of MSA cases with high
      densities of glial cytoplasmic inclusions could be captured by this radioligand.
      (c) 2017 International Parkinson and Movement Disorder Society.

PMID- 28440892
TI  - The effect of adult Early Warning Systems education on nurses' knowledge,
      confidence and clinical performance: A systematic review.
AB  - AIMS: This review aims to determine the effect of adult Early Warning Systems
      education on nurses' knowledge, confidence and clinical performance. BACKGROUND:
      Early Warning Systems support timely identification of clinical deterioration and
      prevention of avoidable deaths. Several educational programmes have been designed
      to help nurses recognize and manage deteriorating patients. Little is known as to
      the effectiveness of these programmes. DESIGN: Systematic review. DATA SOURCES:
      Academic Search Complete, CINAHL, MEDLINE, PsycINFO, PsycARTICLES, Psychology and
      Behavioral Science Collection, SocINDEX and the UK & Ireland Reference Centre,
      EMBASE, the Turning Research Into Practice database, the Cochrane Central
      Register of Controlled Trials (CENTRAL) and Grey Literature sources were searched
      between October and November 2015. REVIEW METHODS: This is a quantitative
      systematic review using Cochrane methods. Studies published between January 2011 
      November 2015 in English were sought. The risk of bias, level of evidence and
      the quality of evidence per outcome were assessed. RESULTS: Eleven articles with
      10 studies were included. Nine studies addressed clinical performance, four
      addressed knowledge and two addressed confidence. Knowledge, vital signs
      recording and Early Warning Score calculation were improved in the short term.
      Two interventions had no effect on nurses' response to clinical deterioration and
      use of communication tools. CONCLUSION: This review highlights the importance of
      measuring outcomes using standardized tools and valid and reliable instruments.
      Using longitudinal designs, researchers are encouraged to investigate the effect
      of Early Warning Systems educational programmes. These can include interactive e
      learning, on-site interdisciplinary Early Warning Scoring systems training
      sessions and simulated scenarios.

PMID- 28440893
TI  - An HPLC method for simultaneous quantitative determination of seven secoiridoid
      glucosides separated from the roots of Ilex pubescens.
AB  - A simple and specific high-performance liquid chromatographic method has been
      developed and validated to simultaneously determine seven secoiridoid glucosides
      for the first time. Three of them were separated from the ethanolic extract of
      the roots of Ilex pubescens for the first time, namely nuezhenide A, ligusides B
      and oleonuezhenide. In quantitative analysis, all of the calibration curves
      showed good linear regression (r > 0.999) within the tested ranges, and the mean
      recoveries of three different concentrations ranged from 97.6 to 101.2%. The
      limit of detection and limit of quantification were <4.18 and 11.63 ng mL-1 ,
      respectively. The relative standard deviation for repeatability and the precision
      of seven analytes were <3.4 and 1.9%, respectively. The established method was
      successfully applied to simultaneous determination of seven secoiridoid
      glucosides in 11 batches of samples collected from different habitats in China.

PMID- 28440894
TI  - Chromatin SUMOylation in heat stress: To protect, pause and organise?: SUMO
      stress response on chromatin.
AB  - Post-translational modifications, e.g. SUMO modifications (SUMOylation), provide
      a mechanism for swiftly changing a protein's activity. Various stress conditions
      trigger a SUMO stress response (SSR) - a stress-induced rapid change in the
      conjugation of SUMO to multiple proteins, which predominantly targets nuclear
      proteins. The SSR has been postulated to protect stressed cells by preserving the
      functionality of crucial proteins. However, it is unclear how it exerts its
      protective functions. Interestingly, heat stress (HS) increases SUMOylation of
      proteins at active promoters and enhancers. In promoters, HS-induced SUMOylation
      correlates with gene transcription and stress-induced RNA polymerase II (Pol2)
      pausing. Conversely, a disappearance of SUMOylation in HS occurs at chromatin
      anchor points that maintain chromatin-looping structures and the spatial
      organisation of chromatin. In reviewing the literature, we hypothesise that the
      SSR regulates Pol2 pausing by modulating the interactions of pausing-regulating
      proteins, whereas deSUMOylation alters the function of chromatin anchors.

PMID- 28440895
TI  - The Relationship between Rate of Algometer Application and Pain Pressure
      Threshold in the Assessment of Myofascial Trigger Point Sensitivity.
AB  - BACKGROUND: Pressure algometry is a commonly employed technique in the assessment
      of both regional and widespread musculoskeletal pain. Despite its acceptance
      amongst clinicians and scientists, the relationship between rate of pressure
      application (RoA) and pain pressure threshold (PPT) remains poorly understood. We
      set out to test the hypothesis that a strong, positive, linear relationship
      exists between the RoA and the PPT within the infraspinatus of young healthy
      subjects. METHODS: Thirty-three participants were randomly recruited from the
      local university community. PPT measures were recorded from a clinically
      identified myofascial trigger point within the right infraspinatus muscle during
      pressure algometry. A total of 2 PPT measures were recorded using each of 3
      different RoAs, including low (15 N/s), medium (35 N/s), and high (55 N/s). Three
      baseline trials were also conducted at 30 N/s. The Pearson's correlation
      coefficient between RoA and PPT was calculated for each subject and averaged
      across participants. RESULTS: The mean(SD) correlation between subjects was 0.77
      (0.19), and the mean (SD) slope of the linear regression was 0.13 (0.09).
      CONCLUSION: Our results demonstrate that there is a strong, linear relationship
      between the RoA and PPT when using the pressure algometry technique. The low
      slope between RoA and PPT suggests clinicians can rely on PPT assessments despite
      small RoA fluctuations. Future research should explore this relationship further
      in a clinical population and in other muscles affected by chronic myofascial
      pain. Advancing cost-effective, reliable, and clinically feasible tools such as
      algometry is important to enhancing the diagnosis and management of chronic
      myofascial pain.

PMID- 28440897
TI  - Sonographic findings in two cases of lymphangioma of the mesocolon in adults.
AB  - Lymphangioma of the mesocolon is very rare. We report two cases of surgically
      resected and histologically proven mesocolic lymphangioma in adults. In both
      cases, ultrasound revealed a large cystic mass with multiple thin septa in the
      lower abdomen. A peculiar finding was the large craniocaudal sliding movement of
      the mass synchronized with the patient's respiration, which was a clue to the
      diagnosis of mesenteric lymphangioma. (c) 2017 Wiley Periodicals, Inc. J Clin
      Ultrasound 46:78-81, 2018.

PMID- 28440896
TI  - Genome-wide meta-analysis identifies a novel susceptibility signal at CACNA2D3
      for nicotine dependence.
AB  - Nicotine dependence (ND) has a reported heritability of 40-70%. Low-coverage
      whole-genome sequencing was conducted in 1,889 samples from the UCSF Family
      study. Linear mixed models were used to conduct genome-wide association (GWA)
      tests of ND in this and five cohorts obtained from the database of Genotypes and
      Phenotypes. Fixed-effect meta-analysis was carried out separately for European (n
      = 14,713) and African (n = 3,369) participants, and then in a combined analysis
      of both ancestral groups. The meta-analysis of African participants identified a
      significant and novel susceptibility signal (rs56247223; p = 4.11 * 10-8 ). Data
      from the Genotype-Tissue Expression (GTEx) study suggested the protective allele
      is associated with reduced mRNA expression of CACNA2D3 in three human brain
      tissues (p < 4.94 * 10-2 ). Sequence data from the UCSF Family study suggested
      that a rare nonsynonymous variant in this gene conferred increased risk for ND (p
      = 0.01) providing further support for CACNA2D3 involvement in ND. Suggestive
      associations were observed in six additional regions in both European and merged
      populations (p < 5.00 * 10-6 ). The top variants were found to regulate mRNA
      expression levels of genes in human brains using GTEx data (p < 0.05): HAX1 and
      CHRNB2 (rs1760803), ADAMTSL1 (rs17198023), PEX2 (rs12680810), GLIS3 (rs12348139),
      non-coding RNA for LINC00476 (rs10759883), and GABBR1 (rs56020557 and
      rs62392942). A gene-based association test further supported the relation between
      GABBR1 and ND (p = 6.36 * 10-7 ). These findings will inform the biological
      mechanisms and development of therapeutic targets for ND.

PMID- 28440898
TI  - Comparing induction of labour with oral misoprostol or Foley catheter at term:
      cost-effectiveness analysis of a randomised controlled multi-centre non
      inferiority trial.
AB  - OBJECTIVE: To assess the costs of labour induction with oral misoprostol versus
      Foley catheter. DESIGN: Economic evaluation alongside a randomised controlled
      trial. SETTING: Obstetric departments of six tertiary and 23 secondary care
      hospitals in the Netherlands. POPULATION: Women with a viable term singleton
      pregnancy in cephalic presentation, intact membranes, an unfavourable cervix
      (Bishop score <6) without a previous caesarean section, were randomised for
      labour induction with oral misoprostol (n = 924) or Foley catheter (n = 921).
      METHODS: We performed economic analysis from a hospital perspective. We estimated
      direct medical costs associated with healthcare utilisation from randomisation
      until discharge. The robustness of our findings was evaluated in sensitivity
      analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per
      women induced with oral misoprostol or Foley catheter. RESULTS: Mean costs per
      woman in the oral misoprostol group and Foley catheter group were ?4470 versus
      ?4158, respectively [mean difference ?312, 95% confidence interval (CI) -?508 to
      ?1063]. Multiple sensitivity analyses did not change these conclusions. However,
      if cervical ripening for low-risk pregnancies in the Foley catheter group was
      carried out in an outpatient setting, with admittance to labour ward only at
      start of active labour, the difference would be ?4470 versus ?3489, respectively
      (mean difference ?981, 95% CI ?225-1817). CONCLUSIONS: Oral misoprostol and Foley
      catheter generate comparable costs. Cervical ripening outside labour ward with a
      Foley catheter could potentially save almost ?1000 per woman. TWEETABLE ABSTRACT:
      Oral misoprostol or Foley catheter for induction of labour generates comparable
      costs.

PMID- 28440900
TI  - Phosphoglycerate dehydrogenase (PHGDH) deficiency without epilepsy mimicking
      primary microcephaly.
AB  - Phosphoglycerate dehydrogenase (PHGDH) deficiency (OMIM 256520) is a rare
      autosomal recessive disorder of serine synthesis, with mostly severe congenital
      microcephaly, caused by mutations in the PHGDH gene. Fourteen patients reported
      to date show severe, early onset, drug resistant epilepsy. In a cohort of
      patients referred for primary microcephaly, compound heterozygosity for two
      unreported variants in PHGDG was identified by exome sequencing in a pair of sibs
      who died aged 4.5 months and 4.5 years. They had severe neurological involvement
      with congenital microcephaly, disorganized EEG, and progressive spasticity, but
      never had seizures. Exome usage in clinical practice is likely to lead to an
      expansion of the clinical spectrum of known disorders.

PMID- 28440901
TI  - Examining student heuristic usage in a hydrogen bonding assessment.
AB  - This study investigates the role of representational competence in student
      responses to an assessment of hydrogen bonding. The assessment couples the use of
      a multiple-select item ("Choose all that apply") with an open-ended item to allow
      for an examination of students' cognitive processes as they relate to the
      assignment of hydrogen bonding within a structural representation. Response
      patterns from the multiple-select item implicate heuristic usage as a
      contributing factor to students' incorrect responses. The use of heuristics is
      further supported by the students' corresponding responses to the open-ended
      assessment item. Taken together, these data suggest that poor representational
      competence may contribute to students' previously observed inability to correctly
      navigate the concept of hydrogen bonding. (c) 2017 by The International Union of
      Biochemistry and Molecular Biology, 45(5):411-416, 2017.

PMID- 28440899
TI  - Lissencephaly: Expanded imaging and clinical classification.
AB  - Lissencephaly ("smooth brain," LIS) is a malformation of cortical development
      associated with deficient neuronal migration and abnormal formation of cerebral
      convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and
      subcortical band heterotopia. Our first classification of LIS and subcortical
      band heterotopia (SBH) was developed to distinguish between the first two genetic
      causes of LIS-LIS1 (PAFAH1B1) and DCX. However, progress in molecular genetics
      has led to identification of 19 LIS-associated genes, leaving the existing
      classification system insufficient to distinguish the increasingly diverse
      patterns of LIS. To address this challenge, we reviewed clinical, imaging and
      molecular data on 188 patients with LIS-SBH ascertained during the last 5 years,
      and reviewed selected archival data on another ~1,400 patients. Using these data
      plus published reports, we constructed a new imaging based classification system
      with 21 recognizable patterns that reliably predict the most likely causative
      genes. These patterns do not correlate consistently with the clinical outcome,
      leading us to also develop a new scale useful for predicting clinical severity
      and outcome. Taken together, our work provides new tools that should prove useful
      for clinical management and genetic counselling of patients with LIS-SBH (imaging
      and severity based classifications), and guidance for prioritizing and
      interpreting genetic testing results (imaging based- classification).

PMID- 28440903
TI  - Triple-Doped Monolayer Graphene with Boron, Nitrogen, Aluminum, Silicon,
      Phosphorus, and Sulfur.
AB  - The structure, stability, electronic properties and chemical reactivity of X/B/N
      triple-doped graphene (TDG) systems (X=Al, Si, P, S) are investigated by means of
      periodic density functional calculations. In the studied TDGs the dopant atoms
      prefer to be bonded to one another instead of separated. In general, the XNB
      pattern is preferred, with the exception of sulfur, which favors the SBN motif.
      The introduction of a third dopant results in a negligible decrease of the
      cohesive energies with respect to the dual-doped graphene (DDG) counterparts.
      Thus, it is expect that these systems can be prepared soon. For SiNB TDG, the
      introduction of the B dopant reduces the gap opening at the K point and restores
      the Dirac cones that are destroyed in SiN DDG. On the contrary, for PNB TDG, the
      bandgap is increased with respect to PN DDG, probably because the introduction of
      B weakens the PN bonding, and thus the electronic structure is rather similar to
      that of P-doped graphene. Finally, with regard to the reactivity of the TDGs, for
      AlNB, PNB, and SNB the carbon atoms are more reactive than in their AlN, PN, and
      SN DDG counterparts. On the contrary, the reactivity of SiNB is lower than that
      of SiN DDG. Therefore, to increase the reactivity of graphene, Al, P, and S
      should be combined with BN motifs.

PMID- 28440902
TI  - Between-visit changes in suicidal ideation and risk of subsequent suicide
      attempt.
AB  - BACKGROUND: While clinicians are expected to routinely assess and address suicide
      risk, existing data provide little guidance regarding the significance of visit
      to-visit changes in suicidal ideation. METHODS: Electronic health records from
      four large healthcare systems identified patients completing the Patient Health
      Questionnaire or PHQ9 at outpatient visits. For patients completing two
      questionnaires within 90 days, health system records and state vital records were
      used to identify nonfatal and fatal suicide attempts. Analyses examined how
      changes in PHQ9 item 9 responses between visits predicted suicide attempt or
      suicide death over 90 days following the second visit. RESULTS: Analyses included
      430,701 pairs of item 9 responses for 118,696 patients. Among patients reporting
      thoughts of death or self-harm "nearly every day" at the first visit, risk of
      suicide attempt after the second visit ranged from approximately 2.0% among those
      reporting continued thoughts "nearly every day" down to 0.5% among those
      reporting a decrease to "not at all." Among those reporting thoughts of death or
      self-harm "not at all" at the first visit, risk of suicide attempt following the
      second visit ranged from approximately 0.2% among those continuing to report such
      thoughts "not at all" up to 1.2% among those reporting an increase to "nearly
      every day". CONCLUSIONS: Resolution of suicidal ideation between visits does
      imply a clinically important reduction in short-term risk, but prior suicidal
      ideation still implies significant residual risk. Onset of suicidal ideation
      between visits does not imply any special elevation compared to ongoing suicidal
      ideation. Risk is actually highest for patients repeatedly reporting thoughts of
      death or self-harm.

PMID- 28440904
TI  - The European Court of Human Rights on planned home birth: resolution of a
      paradoxical ruling.

PMID- 28440905
TI  - Clinical follow-up of women after hypertensive disease in pregnancy.

PMID- 28440907
TI  - The story of CRISPR.

PMID- 28440906
TI  - Familial longevity is characterized by high circadian rhythmicity of serum
      cholesterol in healthy elderly individuals.
AB  - The biological clock, whose function deteriorates with increasing age, determines
      bodily circadian (i.e. 24h) rhythms, including that of cholesterol metabolism.
      Dampening of circadian rhythms has been associated with aging and disease.
      Therefore, we hypothesized that individuals with a familial predisposition for
      longevity have a higher amplitude circadian serum cholesterol concentration
      rhythm. The aim of this study was to investigate circadian rhythmicity of serum
      cholesterol concentrations in offspring of nonagenarian siblings and their
      partners. Offspring from nonagenarian siblings (n = 19), and their partners as
      controls (n = 18), were recruited from the Leiden Longevity Study. Participants
      (mean age 65 years) were studied in a controlled in-hospital setting over a 24-h
      period, receiving three isocaloric meals at 9:00 h, 12:00 h and 18:00 h. Lights
      were off between 23:00 h and 8:00 h. Serum total cholesterol (TC), HDL
      cholesterol (HDL-C), non-HDL-C and triglycerides (TG) were determined every 30
      min over a 24-h period. Serum TC concentrations were higher during day than
      during night in offspring (5.2 vs. 4.7 mm, P < 0.001) and in controls (5.3 vs.
      5.0 mm, P < 0.001). The difference in TC concentrations between day and night
      tended to be greater in offspring than in controls (0.5 vs. 0.3 mm, P = 0.109),
      reaching statistical significance in females (P = 0.045). Notably, the day-night
      serum differences in non-HDL-C were twofold greater in offspring than in controls
      (0.43 vs. 0.21 mm, P = 0.044) and most explicit in females (0.53 vs. 0.22, P =
      0.078). We conclude that familial longevity is characterized by a high circadian
      rhythmicity of non-HDL-C in healthy elderly offspring from nonagenarian siblings.

PMID- 28440908
TI  - Cautious use of platelet as a relevant inducer of liver regeneration following
      partial hepatectomy in patients with metastatic hepatic carcinoma.

PMID- 28440909
TI  - Roles of the PDZ-binding motif of HPV 16 E6 protein in oncogenic transformation
      of human cervical keratinocytes.
AB  - The high-risk human papillomavirus E6 proteins have been shown to interact with
      and lead to degradation of PDZ-domain-containing proteins through its carboxy
      terminal motif. This PDZ-binding motif plays important roles in transformation of
      cultured cells and carcinogenesis of E6-transgenic mice. However, its biological
      effects on the natural host cells have not been elucidated. We have examined its
      roles in an in vitro carcinogenesis model for cervical cancer, in which E6 and E7
      together with activated HRAS (HRASG12V ) can induce tumorigenic transformation of
      normal human cervical keratinocytes. In this model, E6Delta151 mutant, which is
      defective in binding to PDZ domains, almost lost tumorigenic ability, whereas
      E6SAT mutant, which is defective in p53 degradation showed activity close to wild
      type E6. Interestingly, we found decreased expression of PAR3 in E6-expressing
      cells independently of E6AP, which has not been previously recognized. Therefore,
      we knocked down several PDZ-domain containing proteins including PAR3 in human
      cervical keratinocytes expressing E7, HRASG12V and E6Delta151 to examine whether
      depletion of these proteins can restore the tumorigenic ability. Single knockdown
      of SCRIB, MAGI1 or PAR3 significantly but partially restored the tumorigenic
      ability. The combinatorial knockdown of SCRIB and MAGI1 cooperatively restored
      the tumorigenic ability, and additional depletion of PAR3 further enhanced the
      tumorigenic ability surpassing that induced by wild-type E6. These data highlight
      the importance of the carboxy-terminal motif of the E6 protein and downregulation
      of PAR3 in tumorigenic transformation of human cervical keratinocytes.

PMID- 28440910
TI  - Subacute pyridostigmine exposure increases heart rate recovery and cardiac
      parasympathetic tone in rats.
AB  - Heart rate recovery (HRR) describes the rapid deceleration of heart rate after
      strenuous exercise and is an indicator of parasympathetic tone. A reduction in
      parasympathetic tone occurs in patients with congestive heart failure, resulting
      in prolonged HRR. Acetylcholinesterase inhibitors, such as pyridostigmine, can
      enhance parasympathetic tone by increasing cholinergic input to the heart. The
      objective of this study was to develop a rodent model of HRR to test the
      hypothesis that subacute pyridostigmine administration decreases cholinesterase
      activity and accelerates HRR in rats. Ten days after implantation of
      radiotelemetry transmitters, male Sprague Dawley rats were randomized to control
      (CTL) or treated (PYR; 0.14 mg/mL pyridostigmine in the drinking water, 29 days)
      groups. Rats were exercised on a treadmill to record HRR, and blood samples were
      collected on days 0, 7, 14, and 28 of pyridostigmine administration. Total
      cholinesterase and acetylcholinesterase (AChE) activity in plasma was decreased
      by 32%-43% and 57%-80%, respectively, in PYR rats on days 7-28, while plasma
      butyrylcholinesterase activity did not significantly change. AChE activity in red
      blood cells was markedly reduced by 64%-66%. HRR recorded 1 minute after exercise
      was higher in the PYR group on days 7, 14 and 28, and on day 7 when HRR was
      estimated at 3 and 5 minutes. Autonomic tone was evaluated pharmacologically
      using sequential administration of muscarinic (atropine) and adrenergic
      (propranolol) blockers. Parasympathetic tone was increased in PYR rats as
      compared with the CTL group. These data support the study hypothesis that
      subacute pyridostigmine administration enhances HRR by increasing cardiac
      parasympathetic tone.

PMID- 28440911
TI  - Unnoticed aspiration of palate plate impression material in a neonate: Diagnosis,
      therapy, outcome.
AB  - A 7 week old infant was admitted with respiratory failure. Chest X-ray showed an
      atelectatic right upper lobe, herniation of right middle and lower lobe into the
      left thorax, and compression-atelectasis of the left lung. Thoracic CT showed
      complete occlusion of the right superior bronchus with a radiopaque foreign
      material. Six weeks prior, an impression for a palate plate using
      polyvinylsiloxane was taken. The material was removed with a rigid endoscopy, in
      readiness of extracorporeal oxygenation in case of tracheal obstruction or
      bronchial rupture. After 4 months of follow-up a hyper reactive airway with
      recurrent upper and lower airway infections remains.

PMID- 28440913
TI  - Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in
      combination with vancomycin and tobramycin in pediatric cystic fibrosis patients.
AB  - BACKGROUND: Cystic fibrosis (CF) patients often receive prolonged courses of
      broad spectrum antibiotics, such as piperacillin-tazobactam or cefepime in
      combination with vancomycin and tobramycin. The objective of this study was to
      determine the difference in AKI for pediatric CF patients receiving piperacillin
      tazobactam or cefepime in combination with vancomycin and tobramycin. METHODS:
      IRB approval from a single CF center was obtained for this retrospective cohort
      study. Charts were evaluated from December 1, 2008 to June 30,2015. Patients were
      included if they had a diagnosis of CF, age 30 days to 18 years, and received
      intravenous vancomycin, tobramycin, and piperacillin-tazobactam or cefepime. The
      primary outcome was difference of AKI incidence in patients receiving
      piperacillin-tazobactam or cefepime, as defined by modified pediatric risk,
      injury, failure, loss, end stage renal disease (pRIFLE) criteria. RESULTS:
      Seventy-one patients were included with a median (interquartile range) age 11
      years (7-16) and weight 36.2 kg (22.7-50). AKI was identified in 54.5% (18/33) of
      patients receiving piperacillin-tazobactam and 13.2% (5/38) of patients receiving
      cefepime (P <= 0.0001). One patient receiving piperacillin-tazobactam experienced
      acute renal failure. There was a slight difference in length of admission (13 vs
      10 days, P = 0.042), but no difference in days to maximum SCr (6 vs 3, P = 0.127)
      nor FEV1 percent predicted on admission (69% vs 65%, P = 1.00). CONCLUSIONS: AKI
      occurred in nearly 55% of patients with piperacillin-tazobactam therapy versus
      13% of patients with cefepime therapy, which suggests cefepime may be preferred
      in combination with vancomycin and tobramycin for pediatric CF patients.

PMID- 28440914
TI  - Transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B
      FNA)-Pushing the boundaries in the diagnosis.
AB  - Isolated mediastinal adenopathy is a diagnostic challenge in the paediatric
      population, often requiring invasive surgical procedures for diagnosis. We
      describe a novel minimally invasive modality in a 20 month toddler
      transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B
      FNA). This is the youngest reported use of this modality, highlighting
      feasibility, technical issues, safety, and rapid diagnosis leading to expedited
      treatment.

PMID- 28440912
TI  - Performance of in silico tools for the evaluation of p16INK4a (CDKN2A) variants
      in CAGI.
AB  - Correct phenotypic interpretation of variants of unknown significance for cancer
      associated genes is a diagnostic challenge as genetic screenings gain in
      popularity in the next-generation sequencing era. The Critical Assessment of
      Genome Interpretation (CAGI) experiment aims to test and define the state of the
      art of genotype-phenotype interpretation. Here, we present the assessment of the
      CAGI p16INK4a challenge. Participants were asked to predict the effect on
      cellular proliferation of 10 variants for the p16INK4a tumor suppressor, a cyclin
      dependent kinase inhibitor encoded by the CDKN2A gene. Twenty-two pathogenicity
      predictors were assessed with a variety of accuracy measures for reliability in a
      medical context. Different assessment measures were combined in an overall
      ranking to provide more robust results. The R scripts used for assessment are
      publicly available from a GitHub repository for future use in similar assessment
      exercises. Despite a limited test-set size, our findings show a variety of
      results, with some methods performing significantly better. Methods combining
      different strategies frequently outperform simpler approaches. The best
      predictor, Yang&Zhou lab, uses a machine learning method combining an empirical
      energy function measuring protein stability with an evolutionary conservation
      term. The p16INK4a challenge highlights how subtle structural effects can
      neutralize otherwise deleterious variants.

PMID- 28440915
TI  - Unravelling the impact of lignin on cell wall mechanics: a comprehensive study on
      young poplar trees downregulated for CINNAMYL ALCOHOL DEHYDROGENASE (CAD).
AB  - Lignin engineering is a promising tool to reduce the energy input and the need of
      chemical pre-treatments for the efficient conversion of plant biomass into
      fermentable sugars for downstream applications. At the same time, lignin
      engineering can offer new insight into the structure-function relationships of
      plant cell walls by combined mechanical, structural and chemical analyses. Here,
      this comprehensive approach was applied to poplar trees (Populus tremula *
      Populus alba) downregulated for CINNAMYL ALCOHOL DEHYDROGENASE (CAD) in order to
      gain insight into the impact of lignin reduction on mechanical properties. The
      downregulation of CAD resulted in a significant decrease in both elastic modulus
      and yield stress. As wood density and cellulose microfibril angle (MFA) did not
      show any significant differences between the wild type and the transgenic lines,
      these structural features could be excluded as influencing factors. Fourier
      transform infrared spectroscopy (FTIR) and Raman imaging were performed to
      elucidate changes in the chemical composition directly on the mechanically tested
      tissue sections. Lignin content was identified as a mechanically relevant factor,
      as a correlation with a coefficient of determination (r2) of 0.65 between lignin
      absorbance (as an indicator of lignin content) and tensile stiffness was found. A
      comparison of the present results with those of previous investigations shows
      that the mechanical impact of lignin alteration under tensile stress depends on
      certain structural conditions, such as a high cellulose MFA, which emphasizes the
      complex relationship between the chemistry and mechanical properties in plant
      cell walls.

PMID- 28440916
TI  - High-Temperature Crystal Structure and Chemical Bonding in Thermoelectric
      Germanium Selenide (GeSe).
AB  - The discovery of the ultra-high thermoelectric figure of merit of 2.6 in SnSe has
      drawn attention to other lead-free IV-VI orthorhombic semiconductors. GeSe has
      been predicted to possess thermoelectric performances comparable to SnSe. Here, a
      complete structural study is reported of GeSe with temperature by means of high
      resolution synchrotron powder X-ray diffraction. In the orthorhombic phase, the
      evolution of the bond distances with temperature is shown to deviate
      significantly with respect to SnSe. Analysis of the chemical bonding within the
      Quantum Theory of Atoms in Molecules shows that GeSe is ionic with van der Waals
      interlayer interactions. The signature of the N shell lone pair of Ge is also
      evident from both the electron density Laplacian and the ELF topologies.

PMID- 28440917
TI  - ATF3 inhibits the inflammation induced by Mycoplasma pneumonia in vitro and in
      vivo.
AB  - OBJECTIVES: Activating transcription factor-3 (ATF3) is a key regulator of
      inflammatory responses. We aimed to investigate the effects and mechanisms of
      ATF3 on the inflammatory cytokines are induced by Mycoplasma pneumonia (MP).
      STUDY DESIGN: RAW264.7 and mouse peritoneal macrophages were exposed to various
      time with or without MP infection (3, 6, 12, 24, and 48 h), and detect the
      expression of ATF3. Adenovirus-expression of ATF3 (Ad/ATF3) or Ad/betagal was
      transfected into cells which were exposed to MP for 48 h, RT-PCR and ELISA was
      used to evaluate the expression and secretion of TNF-alpha, IL-1beta, IL-6, and
      IL-18. In addition, intravenous administration Ad/ATF3 or Ad/betagal into the
      mice, the secretion of inflammatory cytokines were detected using ELISA. ChIP
      assay was used to determine whether ATF3 can bind to the promoter of Early growth
      response protein 1 (Egr-1). Western blot was used to detect the expression of Egr
      1 and Fyn. RESULTS: ATF3 was increased at 3, 6, 12, and 24 h and the highest
      expression levels occurs in 6 h, there is no significant differences at 24 and 48
      h compared with 0 h or CON group in RAW 264.7. Similar results were seen in mouse
      peritoneal macrophages. Overexpression of ATF3 resulted in the reduction of
      inflammatory cytokines. ChIP assay revealed that ATF3 can bind to the promoter of
      Egr-1. Overexpression of ATF3 inhibited the protein expression of Egr-1 and Fyn;
      conversely, ATF3-deficiency promoted the expression of Egr-1 and Fyn.
      Overexpression of Egr-1 reduced the anti-inflammatory action of ATF3.
      CONCLUSIONS: ATF3 inhibit the expression and release of TNF-alpha, IL-1beta, IL
      6, and IL-18 induced by MP in vitro and in vivo, which is associated with its
      negative regulation of Egr-1/Fyn signaling pathway.

PMID- 28440918
TI  - Uremic pleuritis: A case report and review of recurrent exudative pleural
      effusions in children.
AB  - Despite similar mechanisms driving pleural fluid accumulation, the causes of
      pleural effusions in children differ significantly from that of adults. When a
      pleural effusion re-occurs in an adult, literature recommends early
      thoracentesis, and consideration for pleuroscopy with biopsy to guide the
      diagnostic evaluation. In children, there is a paucity of literature for guiding
      management of recurrent exudative pleural effusion. We present an unusual
      pediatric case of uremic pleuritis with recurrent pericardial and exudative
      pleural effusions.

PMID- 28440919
TI  - Rev7, the regulatory subunit of Polzeta, undergoes UV-induced and Cul4-dependent
      degradation.
AB  - In eukaryotic cells, Rev7 interacts with Rev3 and functions as a regulatory
      subunit of Polzeta, a translesion DNA synthesis (TLS) polymerase. In addition to
      its role in TLS, mammalian Rev7, also known as Mad2B/Mad2L2, participates in
      multiple cellular activities including cell cycle progression and double-strand
      break repair through its interaction with several proteins. Here we show that in
      mammalian cells, Rev7 undergoes ubiquitin/proteasome-mediated degradation upon UV
      irradiation in a time-dependent manner. We identified the Rev7 N-terminal
      destruction box as the degron and Cul4A/B as putative E3 ligases in this process.
      We also show that the nucleotide excision repair (NER) pathway protein HR23B
      physically interacts and colocalizes with Rev7 in the nuclear foci after UV
      irradiation and protects Rev7 from accelerated degradation. Furthermore, a
      similar Rev7 degradation profile was observed in cells treated with the UV
      mimetic agent 4-nitroquinoline 1-oxide but not with cisplatin or camptothecin,
      suggesting a role of the NER pathway protein(s) in UV-induced Rev7 degradation.
      These data and the observation that cells deficient in Rev7 are sensitized to UV
      irradiation while excessive Rev7 protects cells from UV-induced DNA damage
      provide a new insight into the potential interplay between TLS and NER.

PMID- 28440920
TI  - Pediatric pulmonology year in review 2016: Part 2.
AB  - Pediatric Pulmonology continues to publish research and clinical topics related
      to the entire range of children's respiratory disorders. As we have done annually
      in recent years, we here summarize some of the past year's publications in our
      major topic areas, as well as selected literature in these areas from other core
      journals relevant to our discipline. This review (Part 2) covers selected
      articles on neonatology, asthma, physiology and lung function testing, and
      infectious diseases.

PMID- 28440921
TI  - Pediatric Pulmonology year in review 2016: Part 1.
AB  - Pediatric Pulmonology continues to publish research and clinical topics related
      to the entire range of children's respiratory disorders. As we have done annually
      in recent years, we here summarize the past year's publications in our major
      topic areas, as well as selected literature in these areas from other core
      journals relevant to our discipline. This review (Part 1) covers selected
      articles on sleep, diagnostic testing/endoscopy, respiratory complications of
      neuromuscular disorders, and rare lung diseases.

PMID- 28440923
TI  - Ecotoxicity testing of microplastics: Considering the heterogeneity of
      physicochemical properties.
AB  - "Microplastic" is an umbrella term that covers many particle shapes, sizes, and
      polymer types, and as such the physical and chemical properties of environmental
      microplastics will differ from the primary microbeads commonly used for
      ecotoxicity testing. In the present article, we discuss the physical and chemical
      properties of microplastics that are potentially relevant to their ecotoxicity,
      including particle size, particle shape, crystallinity, surface chemistry, and
      polymer and additive composition. Overall, there is a need for a structured
      approach to the testing of different properties to identify which are the most
      relevant drivers of microplastic toxicity. In addition, the properties discussed
      will be influenced by and change depending on environmental conditions and
      degradation pathways. Future challenges include new technologies that will enter
      the plastic production cycle and the impact of these changes on the composition
      of environmental microplastics. Integr Environ Assess Manag 2017;13:470-475. (c)
      2017 SETAC.

PMID- 28440922
TI  - Pseudomonas aeruginosa and post-tracheotomy bacterial respiratory tract infection
      readmissions.
AB  - OBJECTIVE: Identify risk factors for readmission due to a bacterial tracheostomy
      associated respiratory tract infection (bTARTI) within 12 months of discharge
      after tracheotomy. DESIGN/METHODS: We performed a retrospective cohort study of
      240 children who underwent tracheotomy and were discharged with tracheotsomy in
      place between January 1, 2005 and June 30, 2013. Children with prolonged total or
      post-tracheotomy length of stay (LOS), less than 12 months of follow-up, or who
      died during the index hospitalization were excluded. Readmission for a bTARTI
      (eg, pneumonia, tracheitis) treated with antibiotics, as ascertained by manual
      chart review, was the outcome variable. We used multivariate logistic regression
      to identify the independent association between risk factors and hospital
      readmission for bTARTI within 12 months. RESULTS: At index hospitalizations for
      tracheotomy, the median admission age was 5 months (interquartile range [IQR] 2
      43 months) and median LOS was 73 days (IQR 43-121 days). Most patients were of
      Hispanic ethnicity (n = 162, 68%) and were publicly insured (n = 213, 89%).
      Nearly half (n = 112, 47%) were discharged on positive pressure mechanical
      ventilation. Many (n = 103, 43%) were admitted for bTARTI within 12 months of
      discharge. Only Hispanic ethnicity (adjusted odds ratio [AOR] 2.0; 95% confidence
      interval [CI]: 1.1-3.9; P = 0.03) and acquisition of Pseudomonas aeruginosa
      between tracheotomy and discharge from index hospitalization (AOR 3.2; 95%CI: 1.2
      8.3; P = 0.02) were independently associated with increased odds of bTARTI
      readmission, while discharge on gastrointestinal pro-motility agents was
      associated with decreased risk (AOR = 0.4; 95%CI: 0.2-0.8; P = 0.01).
      CONCLUSIONS: Hispanic ethnicity and post-tracheotomy acquisition of P. aeruginosa
      during initial hospitalization are associated with bTARTI readmission.

PMID- 28440924
TI  - Current understanding of microplastics in the environment: Occurrence, fate,
      risks, and what we should do.
AB  - Microplastics pollution has been documented in the global environment, including
      at sea, in freshwater and in atmospheric fallout. Ingestion of microplastics by
      multiple kinds of organisms has been reported and has received increasing
      attention, because microplastics not only act as a source of toxic chemicals but
      also a sink for toxic chemicals. To better understand the great concerns about
      microplastics and associated toxic chemicals potential exposed to the organisms
      ingesting the debris, we should know more about the occurrence, fate, and risks
      of microplastics in the environment. What we should do depends on this better
      understanding. Integr Environ Assess Manag 2017;13:476-482. (c) 2017 SETAC.

PMID- 28440925
TI  - Microplastics in the context of regulation of commercial shellfish aquaculture
      operations.
AB  - Shellfish aquaculture in the Salish Sea (encompassing the Strait of Juan de Fuca,
      Puget Sound, and the Georgia Strait) is a major source of clams, oysters, and
      mussels in the United States and Canada. Plastic gear is necessary for the
      viability of many of these operations. During the past few years, shellfish farm
      permits issued in Washington State have been challenged on various bases that
      have included allegations that the plastic gear is releasing microplastics,
      commonly defined as particles less than 5 mm in diameter. Published survey data
      on sources of marine plastic debris demonstrate the very limited contribution of
      aquaculture gear. Both permits and industry codes of practice provide procedures
      to minimize loss of gear to the marine environment. Plastic gear is also designed
      specifically to maintain its integrity and not degrade in the marine environment.
      Plastic degradation is greatest on beaches with high UV exposure, whereas
      aquaculture gear is mostly underwater and/or covered by biofoulants. Available
      data for microplastics in water, sediment, and biota of the Salish Sea do not
      suggest significant release of microplastics from shellfish aquaculture
      operations. Integr Environ Assess Manag 2017;13:522-527. (c) 2017 SETAC.

PMID- 28440927
TI  - The environmental trade-offs of human existence: Opening eyes wide shut.

PMID- 28440926
TI  - Sources and dispersive modes of micro-fibers in the environment.
AB  - Understanding the sources and distribution of microfibers (MFs) in the
      environment is critical if control and remediation measures are to be effective.
      Microfibers comprise an overwhelming fraction (>85%) of microplastic debris found
      on shorelines around the world. Although primary sources have not been fully
      vetted, until recently it was widely believed that domestic laundry discharges
      were the major source. It was also thought that synthetic fibers and particles
      having dimensions <5 mm easily bypassed filtration and other solid separation
      processes at wastewater treatment plants (WWTPs) and entered oceans and surface
      waters. A more thorough assessment of WWTP effluent discharges indicates,
      however, that fiber and particulate counts do not support the belief that plants
      are the primary vectors for fibers entering the environment. This finding may
      bolster concerns that active and pervasive shedding of fibers from common fabrics
      and textiles could be contributing significantly, via direct pathways, to
      burgeoning environmental loads. Integr Environ Assess Manag 2017;13:466-469. (c)
      2017 SETAC.

PMID- 28440928
TI  - Microplastics as contaminants in commercially important seafood species.
AB  - The ingestion of microplastic fragments, spheres, and fibers by marine mollusks,
      crustaceans, and fish, including a number of commercially important species,
      appears to be a widespread and pervasive phenomenon. Evidence is also growing for
      direct impacts of microplastic ingestion on physiology, reproductive success and
      survival of exposed marine organisms, and transfer through food webs, although
      the ecological implications are not yet known. Concerns also remain over the
      capacity for microplastics to act as vectors for harmful chemical pollutants,
      including plastic additives and persistent organic pollutants, although their
      contribution must be evaluated alongside other known sources. The potential for
      humans, as top predators, to consume microplastics as contaminants in seafood is
      very real, and its implications for health need to be considered. An urgent need
      also exists to extend the geographical scope of studies of microplastic
      contamination in seafood species to currently underrepresented areas, and to
      finalize and adopt standardized methods and quality-assurance protocols for the
      isolation, identification, and quantification of microplastic contaminants from
      biological tissues. Such developments would enable more robust investigation of
      spatial and temporal trends, thereby contributing further evidence as a sound
      basis for regulatory controls. Despite the existence of considerable
      uncertainties and unknowns, there is already a compelling case for urgent actions
      to identify, control, and, where possible, eliminate key sources of both primary
      and secondary microplastics before they reach the marine environment. Integr
      Environ Assess Manag 2017;13:516-521. (c) 2017 SETAC.

PMID- 28440929
TI  - Marine and freshwater microplastic research in South Africa.
AB  - South Africa has a vibrant plastics manufacturing industry, but recycling is
      limited and insufficient with a notable proportion of the unmanaged waste
      entering the environment. South Africa is a developing country with microplastics
      research in its inception. Very little is known about freshwater microplastics,
      and studies on South African marine microplastics are limited but actively being
      pursued. In a water-scarce country, protection of freshwater resources remains a
      priority, but in the face of other socioeconomic issues (poverty, unemployment,
      and HIV/AIDS), it receives insufficiently effective attention. The full impact
      and risks of microplastics pollution in water is yet to be discovered. The risks
      may be enhanced in a developing country where many communities remain largely
      dependent on the land and natural waters. With South Africa being a water-scarce
      country, the quality of its aquatic resources is at an even greater risk with an
      assumed increasing background of microplastics, emphasizing the need for further
      research. A South African Water Research Commission-funded project is being
      undertaken to derive research priorities, but there is an immediate need for
      improved recycling and waste management. Integr Environ Assess Manag 2017;13:533
      535. (c) 2017 SETAC.

PMID- 28440930
TI  - Impacts of changing ocean circulation on the distribution of marine microplastic
      litter.
AB  - Marine plastic pollution is currently a major scientific focus, with attention
      paid to its distribution and impacts within ecosystems. With recent estimates
      indicating that the mass of plastic released to the marine environment may reach
      250 million metric tons by 2025, the effects of plastic on our oceans are set to
      increase. Distribution of microplastics, those plastics measuring less than 5 mm,
      are of increasing concern because they represent an increasing proportion of
      marine litter and are known to interact with species in a range of marine
      habitats. The local abundance of microplastic is dependent on a complex
      interaction between the scale of local plastic sources and prevailing
      environmental conditions; as a result, microplastic distribution is highly
      heterogeneous. Circulation models have been used to predict plastic distribution;
      however, current models do not consider future variation in circulation patterns
      and weather systems caused by a changing climate. In this study, we discuss the
      potential impacts of global climate change on the abundance and distribution of
      marine plastic pollution. Integr Environ Assess Manag 2017;13:483-487. (c) 2017
      SETAC.

PMID- 28440931
TI  - Microplastics as vectors for environmental contaminants: Exploring sorption,
      desorption, and transfer to biota.
AB  - The occurrence and effects of microplastics (MPs) in the aquatic environment are
      receiving increasing attention. In addition to their possible direct adverse
      effects on biota, the potential role of MPs as vectors for hydrophobic organic
      chemicals (HOCs), compared to natural pathways, is a topic of much debate. It is
      evident, however, that temporal and spatial variations of MP occurrence do (and
      will) occur. To further improve the estimations of the role of MPs as vectors for
      HOC transfer into biota under varying MP concentrations and environmental
      conditions, it is important to identify and understand the governing processes.
      Here, we explore HOC sorption to and desorption from MPs and the underlying
      principles for their interactions. We discuss intrinsic and extrinsic parameters
      influencing these processes and focus on the importance of the exposure route for
      diffusive mass transfer. Also, we outline research needed to fill knowledge gaps
      and improve model-based calculations of MP-facilitated HOC transfer in the
      environment. Integr Environ Assess Manag 2017;13:488-493. (c) 2017 SETAC.

PMID- 28440932
TI  - Microplastics in a freshwater environment receiving treated wastewater effluent.
AB  - Small plastic fragments (microplastics or solid particles <5 mm in size or
      "microbeads" used in personal care products and cosmetics) may ultimately find
      their way into aquatic environments. We studied the presence of microplastics
      (particle sizes 53-105 MUm and 106-179 MUm) spatially and temporally in 3
      connected urban lakes being fed by treated wastewater effluent in Lubbock, Texas.
      These lakes also serve as drainage during storm events. Water samples from
      drainage playa wetlands within the city were also collected. Our interest was in
      determining the presence or absence of microplastics in a freshwater environment
      as well as the source apportionment between personal care products (via
      wastewater) and discarded plastics (via runoff). Results showed that average
      concentrations of microplastics in samples collected from lakes ranged from 0.79
      +/- 0.88 mg/L to 1.56 +/- 1.64 mg/L for the 53-105 MUm size fraction and from
      0.31 +/- 0.72 mg/L to 1.25 +/- 1.98 mg/L for the 106-179 MUm size fraction. For
      samples collected from playa wetlands, average microplastic concentrations ranged
      from 0.64 +/- 0.92 mg/L to 5.51 +/- 9.09 mg/L for the 53-105 MUm size fraction
      and from nondetectable (ND) to 1.79 +/- 3.04 mg/L for the 106-179 MUm size
      fraction. Our results (based on comparison of microplastic masses) suggest that
      urban runoff also contributes microplastics to surface water in addition to the
      treated wastewater effluent (in this particular case). The present findings may
      assist in adopting additional monitoring efforts and provide information on the
      potential contribution of secondary microplastic input into aquatic environments.
      Integr Environ Assess Manag 2017;13:528-532. (c) 2017 SETAC.

PMID- 28440933
TI  - What's in a butt? Environmental contamination from airborne cigarette butt
      emissions.

PMID- 28440934
TI  - Determining global distribution of microplastics by combining citizen science and
      in-depth case studies.
AB  - Microplastics (<5 mm) are contaminants of emerging global concern. They have
      received considerable attention in scientific research, resulting in an increased
      awareness of the issue among politicians and the general public. However, there
      has been significant variation in sampling and extraction procedures used to
      quantify microplastics levels. The difference in extraction procedures can
      especially impact study outcomes, making it difficult, and sometimes impossible,
      to directly compare results among studies. To address this, we recently developed
      a standard operating procedure (SOP) for sampling microplastics on beaches. We
      are now assessing regional and global variations in beach microplastics using
      this standardized approach for 2 research projects. Our first project involves
      the general public through citizen science. Participants collect sand samples
      from beaches using a basic protocol, and we subsequently extract and quantify
      microplastics in a central laboratory using the SOP. Presently, we have 80+
      samples from around the world and expect this number to further increase. Second,
      we are conducting 2, in-depth, regional case studies: one along the Dutch coast
      (close to major rivers, a known source of microplastic input into marine
      systems), and the other on the Lesser Antilles in the Caribbean (in the proximity
      to a hotspot of plastics in the North Atlantic Ocean). In both projects, we use
      our new SOP to determine regional variation in microplastics, including
      differences in physicochemical characteristics such as size, shape, and polymer
      type. Our research will provide, for the first time, a systematic comparison on
      levels of microplastics on beaches at both a regional and global scale. Integr
      Environ Assess Manag 2017;13:536-541. (c) 2017 SETAC.

PMID- 28440935
TI  - Learned Discourse: Timely Scientific Opinions.

PMID- 28440936
TI  - Harmonization of water and sediment quality guideline derivation.

PMID- 28440937
TI  - Microplastics are not important for the cycling and bioaccumulation of organic
      pollutants in the oceans-but should microplastics be considered POPs themselves?
AB  - The role of microplastic particles in the cycling and bioaccumulation of
      persistent organic pollutants (POPs) is discussed. Five common concepts,
      sometimes misconceptions, about the role of microplastics are reviewed. While
      there is ample evidence that microplastics accumulate high concentrations of
      POPs, this does not result in microplastics being important for the global
      dispersion of POPs. Similarly, there is scant evidence that microplastics are an
      important transfer vector of POPs into animals, but possibly for plastic
      additives (flame retardants). Last, listing microplastics as POPs could help
      reduce their environmental impact. Integr Environ Assess Manag 2017;13:460-465.
      (c) 2017 SETAC.

PMID- 28440938
TI  - Overstated risk conclusions: Wide-ranging mammals.

PMID- 28440939
TI  - Trophic transfer of microplastics in aquatic ecosystems: Identifying critical
      research needs.
AB  - To evaluate the process of trophic transfer of microplastics, it is important to
      consider various abiotic and biotic factors involved in their ingestion,
      egestion, bioaccumulation, and biomagnification. Toward this end, a review of the
      literature on microplastics has been conducted to identify factors influencing
      their uptake and absorption; their residence times in organisms and
      bioaccumulation; the physical effects of their aggregation in gastrointestinal
      tracts; and their potential to act as vectors for the transfer of other
      contaminants. Limited field evidence from higher trophic level organisms in a
      variety of habitats suggests that trophic transfer of microplastics may be a
      common phenomenon and occurs concurrently with direct ingestion. Critical
      research needs include standardizing methods of field characterization of
      microplastics, quantifying uptake and depuration rates in organisms at different
      trophic levels, quantifying the influence that microplastics have on the uptake
      and/or depuration of environmental contaminants among different trophic levels,
      and investigating the potential for biomagnification of microplastic-associated
      chemicals. More integrated approaches involving computational modeling are
      required to fully assess trophic transfer of microplastics. Integr Environ Assess
      Manag 2017;13:505-509. (c) 2017 SETAC.

PMID- 28440940
TI  - From the sea to the laboratory: Characterization of microplastic as prerequisite
      for the assessment of ecotoxicological impact.
AB  - The presence of microplastic (MP) in the aquatic environment is recognized as a
      global-scale pollution issue. Secondary MP particles result from an ongoing
      fragmentation process governed by various biotic and abiotic factors. For a
      reliable risk assessment of these MP particles, knowledge about interactions with
      biota is needed. However, extensive testing with standard organisms under
      reproducible laboratory conditions with well-characterized MP suspensions is not
      available yet. As MP in the environment represents a mixture of particles
      differing in properties (e.g., size, color, polymer type, surface
      characteristics), it is likely that only specific particle fractions pose a
      threat towards organisms. In order to assign hazardous effects to specific
      particle properties, these characteristics need to be analyzed. As shown by the
      testing of particles (e.g. nanoparticles), characteristics other than chemical
      properties are important for the emergence of toxicity in organisms, and
      parameters such as surface area or size distribution need consideration.
      Therefore, the use of "well-defined" particles for ecotoxicological testing
      (i.e., standard particles) facilitates the establishment of causal links between
      physical-chemical properties of MP particles and toxic effects in organisms.
      However, the benefits of well-defined particles under laboratory conditions are
      offset by the disadvantage of the unknown comparability with MP in the
      environment. Therefore, weathering effects caused by biological, chemical,
      physical or mechanical processes have to be considered. To date, the
      characterization of the progression of MP weathering based on powder and
      suspension characterization methods is in its infancy. The aim of this commentary
      is to illustrate the prerequisites for testing MP in the laboratory from 3
      perspectives: (i) knowledge of particle properties; (ii) behavior of MP in test
      setups involving ecotoxicological test organisms; and (iii) accordingly, test
      conditions that may need adjustment. Only under those prerequisites will reliable
      hazard assessment of MP be feasible. Integr Environ Assess Manag 2017;13:500-504.
      (c) 2017 SETAC.

PMID- 28440941
TI  - Ingestion of microplastics by fish and its potential consequences from a physical
      perspective.
AB  - The European Marine Strategy Framework Directive and the United States Microbead
      Free Waters Act are credited for being ambitious in their goals for protecting
      the marine environment from microplastics pollution. As a result, the
      microplastic pollution of marine environments and the incidence of microplastic
      ingestion by fish is rapidly receiving an increase in overdue attention. This
      commentary summarizes recent discoveries regarding the potential negative effects
      of micro- and nanoplastic ingestion by fish. Analysis shows that the occurrence
      of microplastics in the gastrointestinal tract of fish is ephemeral, with low
      accumulation potential in the gastrointestinal tract, although translocation to
      the liver may occur. Nevertheless, the total load of micro- and nanoplastics that
      will pass through the gastrointestinal tract of a fish in its lifetime is likely
      high and will keep increasing in the future. This may pose a risk because there
      is evidence that micro- and nanoplastic ingestion can interfere with fish health.
      Observed effects of microplastics ingestion include (but are not necessarily
      limited to) intestinal blockage, physical damage, histopathological alterations
      in the intestines, change in behavior, change in lipid metabolism, and transfer
      to the liver. Integr Environ Assess Manag 2017;13:510-515. (c) 2017 SETAC.

PMID- 28440942
TI  - The dangers of overestimating avian risks of pesticides.

PMID- 28440943
TI  - Microplastics as a vector of hydrophobic contaminants: Importance of hydrophobic
      additives.
AB  - Despite a recent boom in research on the environmental fate, distribution, and
      harmful effects of chemical substances associated with marine plastic debris, no
      consensus has been reached on whether chemicals originating from microplastics
      cause serious environmental harm. For the risk assessment of chemical
      contaminants associated with microplastics, it would be useful to group organic
      chemicals into 2 categories: additives and nonadditives. Whereas plastic
      particles are not likely to be diffuse sources of chemicals that are not
      intentionally added to plastic products, continuous leaching of additives would
      result in higher concentrations, at least at a local scale. Unlike plasticizers
      and flame retardants, which have been relatively well investigated, antioxidants
      and photostabilizers have been rarely studied, even though many of them are
      highly hydrophobic and are not readily biodegradable. More research on the fate
      and effects of chemicals via microplastics should focus on those additives.
      Integr Environ Assess Manag 2017;13:494-499. (c) 2017 SETAC.

PMID- 28440944
TI  - The regulatory significance of tag recycling in the mycobacterial Pup-proteasome
      system.
AB  - Pup, a ubiquitin analog, tags proteins for degradation by the bacterial
      proteasome. As an intracellular proteolytic system, the Pup-proteasome system
      (PPS) must be carefully regulated to prevent excessive protein degradation.
      Currently, those factors underlying PPS regulation remain poorly understood.
      Here, experimental analysis combined with theoretical modeling of in vivo protein
      pupylation revealed how the basic PPS design allows stable and controlled protein
      pupylation. Specifically, the recycling of Pup when targets are degraded allows
      the PPS to maintain steady-state levels of protein pupylation and degradation at
      a rate limited by proteasome function, and at a pupylome level limited by Pup
      concentrations. This design allows the Pup-ligase, a highly promiscuous enzyme,
      to act in a controlled manner without causing damage, and the PPS to be
      effectively tuned to control protein degradation. This study thus provides
      understanding of how the inherent design of an intracellular proteolytic system
      serves crucial regulatory purposes.

PMID- 28440946
TI  - What the neighbors say.

PMID- 28440945
TI  - Heterogeneity in esophageal and gastric cardia precursor progression during six
      year endoscopic surveillance after population-based screening in a Chinese high
      risk region.
AB  - BACKGROUND: The study was conducted to examine esophageal and gastric cardia
      precursor progression. METHODS: After population-based baseline screening, 145
      precursor and 335 chronic inflammation cases were endoscopically surveyed for six
      years. RESULTS: Surveillance of interval and baseline diagnoses for 18 severe
      dysplasia (SD) cases later detected were: 13, 23, 39, and 44 months since a
      diagnosis of chronic inflammation in four cases; 6, 6, 6, 11, 13, 16, 16, and 23
      months since mild dysplasia (mD) diagnoses in eight; and 6, 9, 10, 13, 18, and 48
      months since moderate dysplasia (MD) diagnoses in six. Rates for 11 carcinoma in
      situ (Cis) cases later detected were: 7 and 18 months since basal cell
      hyperplasia (Bch) diagnoses in two; and 6, 6, 9, 13, 13, 18, 35, 44, and 50
      months since MD diagnoses in nine. In 10 cancer cases later detected, rates were:
      6, 6, 7, 18, 19, 34, 36, and 48 months since SD diagnoses in eight cases with
      submucosal carcinoma; 46 months since MD diagnosis in a T 2 N 0 M 0 carcinoma
      case; and 52 months since Bch diagnosis in another T 2 N 0 M 0 case. CONCLUSION:
      Esophageal and gastric cardia precursors are heterogeneous. Male gender, advanced
      age, family history of upper gastrointestinal cancer, and multifocal dysplasia
      are significant independent predictors for progression, and Bch/mD, MD, and SD
      constitute three distinctive entities regarding the risk of cancer.

PMID- 28440947
TI  - Regulation of the turnover of ACC synthases by phytohormones and
      heterodimerization in Arabidopsis.
AB  - Ethylene influences many aspects of plant growth and development. The
      biosynthesis of ethylene is highly regulated by a variety of internal and
      external cues. A key target of this regulation is 1-aminocyclopropane-1
      carboxylic acid (ACC) synthases (ACS), generally the rate-limiting step in
      ethylene biosynthesis, which is regulated both transcriptionally and post
      transcriptionally. Prior studies have demonstrated that cytokinin and
      brassinosteroid (BR) act as regulatory inputs to elevate ethylene biosynthesis by
      increasing the stability of ACS proteins. Here, we demonstrate that several
      additional phytohormones also regulate ACS protein turnover. Abscisic acid,
      auxin, gibberellic acid, methyl jasmonic acid, and salicylic acid differentially
      regulate the stability of ACS proteins, with distinct effects on various
      isoforms. In addition, we demonstrate that heterodimerization influences the
      stability of ACS proteins. Heterodimerization between ACS isoforms from distinct
      subclades results in increased stability of the shorter-lived partner. Together,
      our study provides a comprehensive understanding of the roles of various
      phytohormones on ACS protein stability, which brings new insights into crosstalk
      between ethylene and other phytohormones, and a novel regulatory mechanism that
      controls ACS protein stability through a heterodimerization of ACS isoforms.

PMID- 28440948
TI  - Novel reduction-sensitive micellar nanoparticles assembled from Rituximab
      doxorubicin conjugates as smart and intuitive drug delivery systems for the
      treatment of non-Hodgkin's lymphoma.
AB  - In this study, a novel reduction-sensitive drug delivery system, the rituximab
      doxorubicin (RTX-DOX) micellar nanoparticle (RDMN), was specially designed for
      targeted delivery and release of DOX in non-Hodgkin's lymphoma (NHL) cells. The
      RDMN was fabricated by self-assembling of amphiphilic RTX-DOX conjugates (RDCs),
      which were synthesized by conjugating the hydrophilic Fab fragments of RTX (an
      anti-CD20 monoclonal antibody) and hydrophobic DOXs by a reduction-responsive
      linker, 3-(2-Pyridyldithio) propionyl hydrazide (PDPH). The RDMNs were
      characterized via dynamic light scattering and transmission electron microscopy,
      both showed the sizes of approximately 94.1 +/- 14.5 nm with a uniform size
      distribution. Polyplex dissociation, which was indicated by accelerated DOX
      release rate and increased particle size, was observed in the presence of 2.5 mm
      1,4-dithiothreitol due to the cleavage of disulfide bonds in PDPH linkers. In
      vitro transfection assays against human NHL cell line, JeKo-1, showed
      significantly increased uptake for RDMNs, as compared to RDCs and free RTX/DOX.
      Both in and ex vivo experiments demonstrated that RDMNs showed the highest
      therapeutic effect among all the experimental groups. These results suggested
      that this RDMN could be a potential, safe and efficient drug delivery vector,
      which deserves further investigation in the clinic.

PMID- 28440949
TI  - Regulations and policies regarding e-cigarettes.
AB  - Electronic cigarettes (e-cigarettes) are a growing public health concern because
      of a dramatic increase in use by adolescents and the uncertainty of potential
      health impacts. These health concerns and lack of an established federal
      regulatory scheme have led many local and state governments to address the
      regulatory void for e-cigarettes by incorporating them into the statutory
      definition of tobacco or by passing laws specific to the use of e-cigarettes. In
      August 2016, the US Food and Drug Administration issued a final rule deeming e
      cigarettes within their authority; providing uniform requirements like premarket
      approval applications, Harmful and Potentially Harmful Constituents reporting,
      and warning labels; and establishing 18 years as a minimum age of purchase.
      Although the impact on the public's health remains uncertain, regulations and
      laws governing e-cigarettes continue to develop. This review highlights the
      available data regarding safety and public health impacts of e-cigarettes and
      details the status of US regulations and policies affecting their sale and use.
      Cancer 2017;123:3007-14. (c) 2017 American Cancer Society.

PMID- 28440950
TI  - The need to know: The information needs of parents of infants with an
      intellectual disability-a qualitative study.
AB  - AIM: The aim of this study was to explore the information needs of parents of
      infants with an intellectual disability in the first year of life. BACKGROUND:
      Parents whose infant has an intellectual disability need access to information if
      they are to facilitate optimal care for their child. A lack of timely, accurate
      information provision by health professionals, particularly nurses and midwives,
      can increase parental stress and hinder access to the supports they and their
      infant require. DESIGN: A qualitative descriptive methodology was used for the
      study. METHODS: Qualitative interviews were undertaken with parents of 11
      children with intellectual disabilities in Victoria, Australia in 2014. Data were
      analysed using descriptive thematic analysis. FINDINGS: Parents experienced
      challenges accessing quality information during the first year of their child's
      life. Parents required incremental information provision to build a strong
      knowledge base to facilitate optimal care for their infants. Three types of
      knowledge were identified as crucial for parents: knowledge about (1) the
      infant's condition; (2) the infant's specific needs and (3) available supports
      and services. Health professionals were the key resource to access this
      information. CONCLUSION: Health professionals' responsibilities include providing
      relevant, timely information to parents of infants with intellectual
      disabilities. This study conceptualises three types of information parents need
      to develop a strong knowledge base to guide their infant's care and provides
      guidance concerning the optimal timing for the delivery of information.

PMID- 28440951
TI  - Concluding the trilogy: The interaction of 2,2'-dihydroxy-benzophenones and their
      carbonyl N-analogues with human glutathione transferase M1-1 face to face with
      the P1-1 and A1-1 isoenzymes involved in MDR.
AB  - A series of 2,2'-dihydroxybenzophenones and their carbonyl N-analogues were
      studied as potential inhibitors against human glutathione transferase M1-1
      (hGSTM1-1) purified from recombinant E. coli. Their screening revealed an
      inhibition against hGSTM1-1 within a range of 0-42% (25 MUM). The IC50 values for
      the two stronger ones, 16 and 13, were 53.5 +/- 5.6 MUMU and 28.5 +/- 2.5 MUMU,
      respectively. The results were compared with earlier ones for isoenzymes hGSTP1-1
      and hGSTA1-1 involved in MDR. All but one bind more strongly to A1-1, than M1-1
      and P1-1, the latter being a poor binder. An order of potency A1-1 > > M1-1 >  P1
      1 meritted 13, 14 and 16 as the most potent inhibitors with hGSTM1-1. Enzyme
      kinetics with hGSTM1-1 (Km(CDNB) 213 +/- 10 MUMU and Km(GSH) 303 +/- 11 MUMU)
      revealed a competitive modality for 16 (Ki(16)  = 22.3 +/- 1.1 MUMU) and a mixed
      one for 13 versus CDNB (Ki(13)  = 33.3 +/- 1.6 MUM for the free enzyme and Ki(13)
      ' = 17.7 +/- 1.7 MUM for the enzyme-CDNB complex). 5- or 5'-Bromo- or phenyl
      substituted (but not in combination) inhibitors, having a H-bonded oxime weakly
      acidic group of a small volume, are optimal candidates for binding hGSTM1-1. The
      outcome of the isoenzyme trilogy identified good binder leads for the
      investigated GSTs involved in MDR.

PMID- 28440952
TI  - Thyroid cancer incidence among Asian immigrants to Ontario, Canada: A population
      based cohort study.
AB  - BACKGROUND: The highest rates of thyroid cancer are observed in Pacific Island
      nations as well as Australia and Asian countries bordering the Pacific. The
      objective of this study was to determine the risk for thyroid cancer among
      immigrants to Canada from Southeast and East Asia compared with immigrants from
      other regions and nonimmigrants. METHODS: This was a population-based,
      longitudinal cohort study using health care administrative data to examine all
      residents of Ontario without pre-existing thyroid cancer. Individuals were
      followed from January 1997 or 5 years after they became eligible for health care
      coverage in Ontario, whichever came later. Patients were followed until March
      2015 for incident-differentiated thyroid cancer, and then for recurrence.
      RESULTS: The study followed 14,659,733 individuals for a median of 17 years.
      Thyroid cancer incidence was 43.8 cases per 100,000 person-years among Southeast
      Asian immigrants, 28.6 cases per 100,000 person-years among East Asian
      immigrants, 21.5 cases per 100,000 person-years among other immigrants, and 14.5
      cases per 100,000 person-years among nonimmigrants. Incidence was highest among
      immigrants from the Philippines (52.7 cases per 100,000 person-years), South
      Korea (33.5 cases per 100,000 person-years), and China (30.0 cases per 100,000
      person-years). Adjusted hazard ratios for thyroid cancer compared with
      nonimmigrants were 2.66 (95% confidence interval, 2.48-2.84) for Southeast Asian
      immigrants, 1.87 (95% confidence interval, 1.75-2.00) for East Asian immigrants,
      and 1.51 (95% confidence interval, 1.45-1.57) for other immigrants. Immigrants
      were more likely to have papillary histology and stage I cancer. East Asian
      immigrants, but not Southeast Asian immigrants, had a lower risk of recurrence
      (hazard ratio, 0.73 [95% confidence interval, 0.57-0.94] and 1.01 [95% confidence
      interval, 0.81-1.26], respectively). CONCLUSIONS: Immigrants from Southeast and
      East Asia had markedly higher thyroid cancer incidence than nonimmigrants. At
      particularly elevated risk were immigrants from the Philippines, South Korea, and
      China. Cancer 2017;123:3320-5. (c) 2017 American Cancer Society.

PMID- 28440954
TI  - Heart-rate variability indices as predictors of the response to vagus nerve
      stimulation in patients with drug-resistant epilepsy.
AB  - OBJECTIVE: To assess heart-rate variability (HRV) measures of interictal
      electrocardiography (ECG) for drug-resistant epilepsy and to relate the findings
      to the outcome of vagus nerve stimulation (VNS) treatment. METHODS: Time-domain,
      frequency-domain, and nonlinear analyses were used to analyze preoperative HRV
      measures in 32 patients with drug-resistant epilepsy who had received VNS
      implants at the same hospital and 32 healthy age- and sex-matched control
      subjects. HRV measurements based on ambulatory 24 h ECG recordings were analyzed
      to identify seizure reduction 1 year after VNS treatment. Responders were defined
      as having at least 50% seizure reduction 1 year after treatment. RESULTS:
      Patients with drug-resistant epilepsy had significantly lower time domain (SDNN,
      RMSSD, pNN50), frequency domain (VLF, LF, HF, TP), and nonlinear (SD1, SD2) HRV
      measurements than matched healthy controls. None of the analyzed HRV measures of
      the responders differed significantly from their controls, whereas those of the
      nonresponders had significantly lower RMSSD, pNN50, HF, and SD1 than the
      responders. SIGNIFICANCE: The preoperative HRV indices demonstrate that
      nonresponders have more pronounced impairment of their cardiac autonomic function
      than the responders. Presurgical HRV measurements representing parasympathetic
      cardiac control or vagal tone were significantly associated with the
      responsiveness to VNS. Thus the measurements show promise for predicting the
      reduction of seizure frequency after VNS treatment.

PMID- 28440953
TI  - Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the
      uterus: Results of a phase 2 study.
AB  - BACKGROUND: Immunotherapy has changed the therapeutic landscape in oncology.
      Advanced uterine leiomyosarcoma (ULMS) remains an incurable disease in most
      cases, and despite new drug approvals, improvements in overall survival have been
      modest at best. The goal of this study was to evaluate programmed-death 1 (PD-1)
      inhibition with nivolumab in this patient population. METHODS: This single-center
      phase 2 trial completed enrollment between May and October 2015. Patients
      received 3 mg/kg of intravenous nivolumab on day 1 of each 2-week cycle until
      disease progression or unacceptable toxicity. The primary endpoint was objective
      response rate. We assessed PD-1, PD-ligand 1 (PD-L1), and PD-L2 expression in
      archival tumor samples and variations in immune-phenotyping of circulating immune
      cells during treatment. RESULTS: Twelve patients were enrolled in the first stage
      of the 2-stage design. A median of 5 (range, 2-6) 2-week cycles of nivolumab were
      administered. Of the 12 patients, none responded to treatment. The overall median
      progression-free survival was 1.8 months (95% confidence interval, 0.8-unknown).
      The study did not open the second stage due to lack of benefit as defined by the
      statistical plan. Archival samples were available for 83% of patients. PD-1 (>3%
      of cells), PD-L1, and PD-L2 (>5% and >10% of tumor cells, respectively)
      expression were observed in 20%, 20%, and 90% of samples, respectively. No
      significant differences were observed between pre- and posttreatment cell
      phenotypes. CONCLUSION: Single-agent nivolumab did not demonstrate a benefit in
      this cohort of previously treated advanced ULMS patients. Further biomarker
      driven approaches and studies evaluating combined immune checkpoint-modulators
      should be considered. Cancer 2017;123:3285-90. (c) 2017 American Cancer Society.

PMID- 28440956
TI  - Doctoral snobbery: Justified, or just elitism?

PMID- 28440955
TI  - Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate
      receptor alpha-targeting antibody-drug conjugate, in patients with solid tumors.
AB  - BACKGROUND: Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate
      that selectively targets folate receptor alpha (FRalpha). In this phase 1 dose
      escalation study, the authors investigated IMGN853 in patients with FRalpha
      positive solid tumors. METHODS: Patients received IMGN853 on day 1 of a 21-day
      cycle (once every 3 weeks dosing), with cycles repeated until patients
      experienced dose-limiting toxicity or progression. Dose escalation commenced in
      single-patient cohorts for the first 4 planned dose levels and then followed a
      standard 3 + 3 scheme. The primary objectives were to determine the maximum
      tolerated dose and the recommended phase 2 dose. Secondary objectives were to
      determine safety and tolerability, to characterize the pharmacokinetic profile,
      and to describe preliminary clinical activity. RESULTS: In total, 44 patients
      received treatment at doses escalating from 0.15 to 7.0 mg/kg. No meaningful drug
      accumulation was observed with the dosing regimen of once every 3 weeks. The most
      common treatment-related adverse events were fatigue, blurred vision, and
      diarrhea, the majority of which were grade 1 or 2. The dose-limiting toxicities
      observed were grade 3 hypophosphatemia (5.0 mg/kg) and grade 3 punctate keratitis
      (7.0 mg/kg). Two patients, both of whom were individuals with epithelial ovarian
      cancer, achieved confirmed tumor responses according to Response Evaluation
      Criteria in Solid Tumors 1.1, and each was a partial response. CONCLUSIONS:
      IMGN853 demonstrated a manageable safety profile and encouraging preliminary
      clinical activity, particularly in patients with ovarian cancer. The results
      establish a recommended phase 2 dosing of 6.0 mg/kg (based on adjusted ideal body
      weight) once every 3 weeks. Cancer 2017. (c) 2017 American Cancer Society. Cancer
      2017;123:3080-7. (c) 2017 American Cancer Society.

PMID- 28440957
TI  - The role of high-throughput screening in ecotoxicology and engineered
      nanomaterials.
AB  - The field of environmental toxicology developed as a result of growing concerns
      about anthropogenic influences on the environment and how to ameliorate
      ecological impact. Many governmental bodies are beginning to emphasize prevention
      rather than mitigation when addressing novel products, leading to more of a focus
      on identifying potential toxicity prior to release. With the exponential advances
      in their development and sale, novel metamaterials and biotechnology are set to
      dramatically outpace the capabilities of current testing strategies. To address
      the need for a fast, cost-effective means of testing chemicals, high-throughput
      screening (HTS) is currently being used in toxicology and being adapted to
      ecotoxicology in projects such as ToxCast and Tox21. Despite the growth of
      research using HTS platforms, its role in ecotoxicology is still uncertain,
      particularly in how it should be applied in regulation. The aim of the present
      review is to discuss common test strategies used in designing HTS platforms, the
      current potential applications for ecotoxicological research, its role in
      regulatory policies, and its ability to address growing concerns such as
      engineered nanomaterials. Environ Toxicol Chem 2017;36:1704-1714. (c) 2017 SETAC.

PMID- 28440958
TI  - Readiness for hospital discharge: A concept analysis.
AB  - AIM: To report on an analysis on the concept of 'readiness for hospital
      discharge'. BACKGROUND: No uniform operational definition of 'readiness for
      hospital discharge' exists in the literature; therefore, a concept analysis is
      required to clarify the concept and identify an up-to-date understanding of
      readiness for hospital discharge. Clarity of the concept will identify all uses
      of the concept; provide conceptual clarity, an operational definition and
      direction for further research. DESIGN: Literature review and concept analysis.
      METHOD: A review of literature was conducted in 2016. Databases searched were:
      Academic Search Complete, CINAHL Plus with Full Text, PsycARTICLES, Psychology
      and Behavioural Sciences Collection, PsycINFO, Social Sciences Full Text (H.W.
      Wilson) and SocINDEX with Full Text. No date limits were applied. RESULTS:
      Identification of the attributes, antecedents and consequences of readiness for
      hospital discharge led to an operational definition of the concept. The following
      attributes belonging to 'readiness for hospital discharge' were extracted from
      the literature: physical stability, adequate support, psychological ability, and
      adequate information and knowledge. CONCLUSION: This analysis contributes to the
      advancement of knowledge in the area of hospital discharge, by proposing an
      operational definition of readiness for hospital discharge, derived from the
      literature. A better understanding of the phenomenon will assist healthcare
      professionals to recognize, measure and implement interventions where necessary,
      to ensure patients are ready for hospital discharge and assist in the advancement
      of knowledge for all professionals involved in patient discharge from hospital.

PMID- 28440959
TI  - Qualitative research in teen experiences living with food-induced anaphylaxis: A
      meta-aggregation.
AB  - AIM: To describe the central experiences of teens living with food-induced
      anaphylaxis as a first step in responding to healthcare needs in this population.
      BACKGROUND: As prevalence of allergy increases and commonly outgrown allergies
      persist longer, chronic management for teens becomes increasingly important.
      Synthesizing existing research helps to recognize management needs specific to
      teens with food allergy. DESIGN: Meta-aggregation for qualitative systematic
      review, to create synthesis for clinical improvement; guided by Joanna Briggs
      Institute methods and their Qualitative Assessment and Review Instrument. DATA
      SOURCES: Seven relevant databases were searched for original qualitative research
      July 2015; 10 studies (published 2007-2015) met inclusion criteria. REVIEW
      METHODS: Both authors undertook critical appraisal, with consensus by discussion.
      Findings from line-by-line extraction were grouped into categories and syntheses.
      In studies with mixed populations, we included only teens (age 12-19) with food
      induced anaphylaxis. RESULTS: We developed three syntheses from nine categories
      and 64 subcategories to reflect central experiences of teens with food-induced
      anaphylaxis, including: (1) defining the allergic self; (2) finding a balance and
      (3) controlling the uncontrollable. The syntheses encompass importance of
      allergic identity/understanding, difficulties in coping with burdens of food
      allergy and reflect the complex risk interactions teens must negotiate in social
      contexts. CONCLUSION: There is a need to respect teens as active participants in
      managing food-induced anaphylaxis, while recognizing that social expectations and
      a lack of public awareness/safety can dangerously affect one's needs and
      decisions. This helps broaden how we conceptualize the needs of teens living with
      food-induced anaphylaxis, informing ongoing care and management.

PMID- 28440960
TI  - Is humidified better than non-humidified low-flow oxygen therapy? A systematic
      review and meta-analysis.
AB  - AIMS: To determine the effects of low-flow oxygen therapy with humidified or non
      humidified oxygen in adult patients. BACKGROUND: Although non-humidified oxygen
      in low-flow oxygen therapy is recommended by many guidelines, humidifying oxygen
      regardless of oxygen flow has been routinely performed in China and Japan and
      further studies are needed to evaluate the evidence. DESIGN: A systematic review
      and meta-analysis that comply with the recommendations of the Cochrane
      Collaboration were conducted. DATA SOURCES: Studies (1980-2016) were identified
      by searching PUBMED, EMBASE, Science Direct, Cochrane library, CNKI and Wanfang
      Database. METHODS: We performed a comprehensive, systematic meta-analysis of
      randomized controlled trials on the efficacy of humidified and non-humidified low
      flow oxygen therapy. Summary risk ratios or weighted mean differences with 95%
      confidence intervals were calculated using a fixed- or random-effects model.
      RESULTS: Twenty-seven randomized controlled trials with a total number of 8,876
      patients were included. Non-humidified oxygen offers more benefits in reducing
      the bacterial contamination of humidifier bottles, as shown by the mean operating
      time for oxygen administration and the respiratory infections compared with
      humidified oxygen therapy. No significant differences were found in dry nose, dry
      nose and throat, nosebleed, chest discomfort, the smell of oxygen and SpO2
      changes. CONCLUSIONS: The routine humidification of oxygen in low-flow oxygen
      therapy is not justifiable and non-humidified oxygen tends to be more beneficial.
      However, considering that the quality of most included studies is poor,
      rigorously designed, large-scale randomized controlled trials are still needed to
      identify the role of non-humidified oxygen therapy.

PMID- 28440961
TI  - A Nonbactericidal Zinc-Complexing Ligand as a Biofilm Inhibitor: Structure-Guided
      Contrasting Effects on Staphylococcus aureus Biofilm.
AB  - Zinc-complexing ligands are prospective anti-biofilm agents because of the
      pivotal role of zinc in the formation of Staphylococcus aureus biofilm.
      Accordingly, the potential of a thiosemicarbazone (compound C1) and a
      benzothiazole-based ligand (compound C4) in the prevention of S. aureus biofilm
      formation was assessed. Compound C1 displayed a bimodal activity, hindering
      biofilm formation only at low concentrations and promoting biofilm growth at
      higher concentrations. In the case of C4, a dose-dependent inhibition of S.
      aureus biofilm growth was observed. Atomic force microscopy analysis suggested
      that at higher concentrations C1 formed globular aggregates, which perhaps formed
      a substratum that favored adhesion of cells and biofilm formation. In the case of
      C4, zinc supplementation experiments validated zinc complexation as a plausible
      mechanism of inhibition of S. aureus biofilm. Interestingly, C4 was nontoxic to
      cultured HeLa cells and thus has promise as a therapeutic anti-biofilm agent. The
      essential understanding of the structure-driven implications of zinc-complexing
      ligands acquired in this study might assist future screening regimes for
      identification of potent anti-biofilm agents.

PMID- 28440962
TI  - Designed Heme-Cage beta-Sheet Miniproteins.
AB  - The structure and function of naturally occurring proteins are governed by a
      large number of amino acids (>=100). The design of miniature proteins with
      desired structures and functions not only substantiates our knowledge about
      proteins but can also contribute to the development of novel applications.
      Excellent progress has been made towards the design of helical proteins with
      diverse functions. However, the development of functional beta-sheet proteins
      remains challenging. Herein, we describe the construction and characterization of
      four-stranded beta-sheet miniproteins made up of about 19 amino acids that bind
      heme inside a hydrophobic binding pocket or "heme cage" by bis-histidine
      coordination in an aqueous environment. The designed miniproteins bound to heme
      with high affinity comparable to that of native heme proteins. Atomic-resolution
      structures confirmed the presence of a four-stranded beta-sheet fold. The heme
      protein complexes also exhibited high stability against thermal and chaotrope
      induced unfolding.

PMID- 28440963
TI  - Clinical sequencing using a next-generation sequencing-based multiplex gene assay
      in patients with advanced solid tumors.
AB  - Advances in next-generation sequencing (NGS) technologies have enabled physicians
      to test for genomic alterations in multiple cancer-related genes at once in daily
      clinical practice. In April 2015, we introduced clinical sequencing using an NGS
      based multiplex gene assay (OncoPrime) certified by the Clinical Laboratory
      Improvement Amendment. This assay covers the entire coding regions of 215 genes
      and the rearrangement of 17 frequently rearranged genes with clinical relevance
      in human cancers. The principal indications for the assay were cancers of unknown
      primary site, rare tumors, and any solid tumors that were refractory to standard
      chemotherapy. A total of 85 patients underwent testing with multiplex gene assay
      between April 2015 and July 2016. The most common solid tumor types tested were
      pancreatic (n = 19; 22.4%), followed by biliary tract (n = 14; 16.5%), and tumors
      of unknown primary site (n = 13; 15.3%). Samples from 80 patients (94.1%) were
      successfully sequenced. The median turnaround time was 40 days (range, 18-70
      days). Potentially actionable mutations were identified in 69 of 80 patients
      (86.3%) and were most commonly found in TP53 (46.3%), KRAS (23.8%), APC (18.8%),
      STK11 (7.5%), and ATR (7.5%). Nine patients (13.0%) received a subsequent therapy
      based on the NGS assay results. Implementation of clinical sequencing using an
      NGS-based multiplex gene assay was feasible in the clinical setting and
      identified potentially actionable mutations in more than 80% of patients. Current
      challenges are to incorporate this genomic information into better therapeutic
      decision making.

PMID- 28440964
TI  - Effect of B9 and B12 vitamin intake on semen parameters and fertility of men with
      MTHFR polymorphisms.
AB  - The methylenetetrahydrofolate reductase (MTHFR) gene codes a crucial enzyme which
      involve in folate metabolism. The effect of MTHFR gene polymorphisms on male
      fertility status is uncertain and controversial. We evaluated the effect of B
      vitamin family intake on total homocysteine content and semen parameters of men
      with MTHFR gene polymorphisms. MTHFR genotypes frequency and serum total
      homocysteine concentration were measured among 280 men with impaired
      spermatogenesis (asthenospermia, oligospermia, severe oligospermia and
      azoospermia) and 85 control participants. B vitamin family dietary intakes were
      assessed using a semi-quantitative food-frequency questionnaire. In addition,
      concentrations of vitamins B9 and B12 were evaluated in serum samples of some
      participants (n = 60). We observed significantly higher frequency of TC or TT
      genotypes in C677T polymorphism among oligospermic, severe oligospermic and
      azoospermic men. CC genotype of A1298C polymorphism was significantly higher only
      in azoospermic men. Also, we observed critical effect of vitamin B9 and B12
      intake on decreasing of total homocysteine and improving of semen parameters
      among the men with T allele of MTHFR C677T polymorphism. Our investigation showed
      that sufficient consumption of vitamins B9 and B12 influences sperm parameters of
      men with different MTHFR polymorphisms, especially genotypes with T allele.

PMID- 28440965
TI  - Concurrent pulmonary sequestration and pulmonary hydatid cyst in a child: A case
      report.
AB  - Pulmonary sequestration (PS) happens when an area of the lung receives its
      arterial blood supply from systemic circulation, resulting in a non-functional
      lesion (Intralobar or extralobar). Hydatid cyst results from infection of the
      tapeworm Echinococcus. We report a case of hydatid cyst existed concurrently with
      intralobar PS. A 12-year-old girl presented with recurrent hemoptysis of 2 years
      duration. Serology for Echinococcus granulosus was positive. CT chest suggested
      intralobar PS in the right middle lobe, which was surgically removed. In
      conclusion, recurrent localized pulmonary infections should raise the suspicion
      of intralobar PS which may rarely coexist with hydatid cyst.

PMID- 28440966
TI  - Lead Levels in Vegetables from Artisanal Mining Sites of Dilimi River, Bukuru and
      Barkin Ladi North Central Nigeria: Cancer and Non-Cancer Risk Assessment
AB  - Lead (Pb) contamination of foods and especially of frequently consumed vegetables
      is a growing public healthconcern worldwide. Although levels of exposure in
      developed countries have declined over the past decades, thesame cannot be said
      of developing countries. Health risk assessment has increasingly been employed to
      determine thepotential hazard of heavy metal exposure to humans. In this study
      vegetable samples (tomatoes, red pepper, brown beans,lettuce, cabbage, Irish
      potatoes, onions, green beans and carrot), soil samples, irrigation water and
      sediment sampleswere collected from the Dilimi River, Bukuru and Barkin Ladi
      communities in north central Nigeria and analyzed forPb content using atomic
      absorption spectroscopy. The results showed levels with ranges from 0.5 - 2.4
      mg/kg (DilimiRiver), 0.3 - 1.7 mg/kg (Barkin Ladi) and 1.46 - 1.89 mg/kg (Bukuru)
      in vegetables were largely above the maximumpermissible limit recommended by
      WHO/FAO. The lead levels found in soil samples, which ranged from 9.19 -
      36.042mg/kg, also exceeded some safety standards. At least 75% of the calculated
      estimated daily intakes of Pb from differentvegetable samples were also higher
      than the permissible tolerable daily intakes PTDI (0.0035 mg/kg day-1) of Pb
      inboth adults and children. Target hazard quotient THQ values > 1 were also
      observed in children. In conclusion, thereis a health risk from consumption of
      vegetables in these mining communities.

PMID- 28440967
TI  - Toxicity of Cisplatin-Loaded Poly Butyl Cyanoacrylate Nanoparticles in a Brain
      Cancer Cell Line: Anionic Polymerization Results
AB  - Cancer is one of the most important issues in modern medicine and the most common
      cause of death aftercardiovascular diseases in many countries. Brain cancer is
      one of the most common causes of cancer death among menand women, ranking third.
      Chemotherapeutic drugs that aim to prevent uncontrolled proliferation of cells in
      tissues ofthe body and induce apoptosis of tumor cells are prominent candidates
      for development. Since cisplatin has an apoptosisinducingrole, it is widely used
      as an anticancer agent. In this research, toxicity of cisplatin was studied with
      the C6rat glioma cell lined using the MTT method. In addition, nanoparticles
      underwent SEM microscopic imaging. Particleaverage size, size distribution,
      polydispersity index (PDI) and zeta potential of poly butyl cyanoacrylate
      nanoparticleswere found to be 222 nm, 0.470 +/- 0.04 and 5.1 +/- 0.2 mV,
      respectively. The results showed that nanoconjugates ofcisplatin have more
      cytotoxic effects on C6 cells than the free drug (P<0.05), pointing to an
      enhanced potential of thesynthesized nano-particles as a new nanocarrier for
      chemotherapy.

PMID- 28440968
TI  - The Effects of Active Hexose Correlated Compound (AHCC) on Levels of CD4+ and
      CD8+ in Patients with Epithelial Ovarian Cancer or Peritoneal Cancer Receiving
      Platinum Based Chemotherapy
AB  - Background: Adjuvant chemotherapy is a required treatment for most patients with
      epithelial ovarian cancer(EOC) or peritoneal cancer. However, it has many adverse
      events which may affect oncologic outcomes. Active hexosecorrelated compound
      (AHCC) has been reported to be an immunoenhancer to decrease adverse events of
      chemotherapy.Materials and Methods: Patients were randomized and allocated to
      receive either AHCC three grams/day (500mg/capsule) or placebo. These drugs were
      administrated as two capsules orally three times a day throughout six cycles
      ofchemotherapy. The primary outcome was a change of CD4+ and CD8+ T cell
      lymphocytes in peripheral blood samplesfrom baseline to completion of
      chemotherapy. Secondary outcomes were rate of bone marrow suppression,
      adverseevents and quality of life (QOL) as assessed by Thai version of the
      Functional Assessment of Cancer Therapy-General(FACT-G). Results: Study outcomes
      were analyzed in 28 patients, 14 patients in each group. Changes in CD4+ and
      CD8+T cell lymphocytes levels were not significantly different between AHCC and
      placebo group; 43.5/ul (-237.5, 143.3)versus -69.5 /ul (-223.8, 165) for CD4+
      level, p=0.61 and 49.5.0 /ul (-80, 153.3) versus 4.0 /ul (-173, 62.5) for
      CD8+level, p=0.19. However, CD8+ levels were significantly higher in the AHCC
      group at the sixth cycle of chemotherapy;392.5.0 /ul (310.8, 598) versus 259.5
      /ul (170.5, 462.3), p=0.03. There was no difference in bone marrow suppressionand
      QOL between the two groups. Adverse events in terms of nausea and vomiting
      significantly decreased but musclepain significantly increased in the AHCC group.
      Conclusions: Changes in CD4+ and CD8+ T cell lymphocytes frombaseline were not
      significantly increased in AHCC group. However, CD8+T cell lymphocytes levels
      were significantlyhigher in the AHCC group at the sixth cycle of chemotherapy.

PMID- 28440969
TI  - Evolution of Cancer Registration Combining Online Reporting with Follow-up in the
      Community: Practices in Guangzhou, China
AB  - Background: An efficient registration system with accurate and timely information
      on cancer incidence andmortality is key to development of policies to prevent and
      control cancer. A traditional registration system usually needs3-4 years to
      collect data and publish a cancer report. However, researchers, policymakers and
      healthcare professionalsneed to know the latest cancer registration data quickly.
      Methods: A computer system has been operating with casesreported online by
      hospitals and followed up in communities at the Cancer Registry of Guangzhou
      (CRG) since 2008.The comparability, completeness, accuracy and timeliness of
      collected data were here evaluated. Results: From 2010to 2014, 181,194 cancer
      cases from 1,916,253 medical records of cancer were reported to the CRG online.
      53,473 caseswere deleted as duplicates (47,906), wrong diagnoses (410) or
      residents of other places (5,157) during the follow up.Successful final follow-up
      rates were over 90% for both newly and previously diagnosed cases by general
      practitionersin community clinics. The CRG coding and classification system
      follows international standards. The annual trendsfor all sites by sex were
      stable from 2010 to 2014. All age-specific incidence rates for childhood cancers
      were withinthe limits of the respective international references. The overall M:I
      ratio for all sites but C44 was 56.7%.,ratios formost sites in Guangzhou being
      between Hong Kong and Shanghai. A total of 75.7% of the cancer cases reported
      in2010-2012 were morphologically verified. Ninety five percent of new cases
      completed registration within 29.0 monthsin 2010, reducing to 8.0 months in 2014.
      Conclusion: The online report system with community follow up at the CRGyields
      reasonably accurate and close-to-complete data. It takes less time to confirm
      diagnosis and other information sothat reporting annual incidence one year after
      the close of registration becomes possible.

PMID- 28440970
TI  - Factors Associated with Cigarette Smoking in Central Parts of Iran
AB  - Background: This study aims to assess factors associated with cigarette smoking
      in central parts of Iran. Materialsand methods: We used the data of the post
      intervention phase of Isfahan Healthy Heart Program (IHHP) that wasconducted in
      2007. Logistic regression was used for calculating crude and adjusted Odds Ratios
      (OR). The group withthe least prevalence of smoking was considered as the
      Reference Group (RG) and the OR for other parts of the variablewas calculated
      based on the RG and reported with a confidence interval of 95%. Findings:
      Generally, 9513 individualsparticipated in the study, of which 13.5% were smokers
      (26.2% of men and 0.8% of women). The OR for cigarettesmoking in men compared
      with women in (RG) was 13.89 (95% Confidence Interval (CI) 7.44-24.82). Among
      ruralareas, compared with urban areas in (RG), the OR was 0.98 (95% CI 0.82
      1.15); and among elementary educationlevel compared to illiterate individuals the
      OR was 4.37 (95% CI 1.68-10.76). The OR in individuals in the age group35-44,
      compared with the age group of 65 and older in (RG) was 2.49 (95% CI 1.81-3.45).
      The place most used forcigarette smoking was streets (72.1%); and the main reason
      for starting or continuing cigarette smoking, accordingto smokers' opinions, was
      pleasure and fun. Conclusion: The highest number of smokers was in 35-44 years
      men, inrural areas, with elementary education level; so, they are the ones who
      need more attention through implementation ofeducational programs for awareness,
      improved attitudes and practices, and smoking cessation programs.

PMID- 28440971
TI  - Prognostic Factors for Large Symptomatic Gists: a Pragmatic Study of Experiences
      From a University Hospital Over 10 Years
AB  - Background: Gastrointestinal stromal tumors (GISTs), which are mesenchymal
      neoplasms in the gastrointestinal (GI)tract account for 0.2% of all GI tumors.
      Several factors have been reported (mostly from studies conducted in
      Westerncountries) to be associated with survival in GISTs cases such as tumor
      site, staging, and tumor size. We conducteda pragmatic study, looking at a 10
      year period, aimed at understanding the prognostic factors related to GISTs in
      auniversity hospital. The study population consisted of patients with large
      symptomatic GISTs. Methods: This wasa retrospective study conducted at the
      Department of Surgery in the Khon Kaen University Hospital (Thailand).
      Allpatients diagnosed with GISTs that were treated between 2006 and 2015 were
      consecutively enrolled. The diagnosis ofGISTs was made by examining the
      pathological section and immunohistochemistry results. The outcome of this
      studywas the rate of survival after surgical treatment. Prognostic factors were
      determined using Cox regression analysis.Results: There were 124 GISTs patients
      treated at the university hospital during the 10-year period of the study.
      Themedian age of all patients was 54 years (range 24-83 years). Of those, 119
      (95.9%) were symptomatic. RectosigmoidGISTs accounted for 20.2% of all tumors.
      The median tumor size was 8 cm. A total of 68 patients (54.8%) died. Themedian
      survival time for all patients was 7.18 years (1st -3rd quartile range 6.48
      7.89). There were three significantfactors associated with death including male
      gender, liver metastasis, and peritoneal metastasis. Conclusion: Malegender,
      liver metastasis, and peritoneal metastasis were prognostic factors for large
      symptomatic GISTs.

PMID- 28440972
TI  - A Comparison between the Diagnostic Accuracy of Frozen Section and Permanent
      Section Analyses in Central Nervous System
AB  - Objective: Using diagnostic pathological methods during surgery is a valuable
      means of determining the appropriatemanagement for patients. Application of
      Frozen Section in CNS surgeries might face challenges due to friability ofbrain
      tissue and its relative inaccessibility. Various studies have evaluated the
      diagnostic acuity of frozen sectioncompared to gold standard but results have
      been quite inconsistent. We conducted the present study to evaluate theaccuracy
      of cryostat in diagnosing central nervous system tumors compared to the Gold
      Standard method. Methods:In this descriptive retrospective study, patients with
      definite diagnosis of central nervous system tumors made throughhistopathological
      evaluations were identified by reviewing the archives of pathology reports during
      1996-2013.Demographic data, clinical history, radiologic findings and results of
      pathologic evaluations were extracted from themedical records and entered into
      SPSS statistical software v.22 for analysis. Results: A total of 405 patients
      diagnosedwith CNS tumors were identified, of which 16 patients were not eligible
      and eventually 389 patients were includedin the study. Regarding tumor category,
      subtype and grade, the results of the two methods were totally compatible in303
      patients (77.9%) and discrepant in 22.1% of cases. The tumors located in the
      middle fossa (p=0.031; OR=2.27;95% CI: 1.08-4.79) and the posterior fossa
      (p=0.021; OR=2.46; 95% CI: 1.15-5.26) and the tumors biopsied using
      thestereotactic method (p=0.050; OR=2.42; 95% CI: 1.001-5.83) were associated
      with an increased chance of discrepantresults between the two methods.
      Conclusion: Frozen section can correctly diagnose and affect the management ofCNS
      lesions in 77.9% of cases. Finding ways to increase the sensitivity and
      specificity of this method and providingsurgeons with more definite and exact
      intra-operative diagnosis can improve management of central nervous systemlesions
      to a considerable degree.

PMID- 28440973
TI  - Histochemical and Immunohistochemical Study of alpha-SMA, Collagen, and PCNA in
      Epithelial Ovarian Neoplasm
AB  - Background: Alpha-smooth muscle actin (alpha-SMA) is an isoform of actin,
      positive in myofibroblasts and is anepithelial to mesenchymal transition (EMT)
      marker. EMT is a process by which tumor cells develop to be more hostileand able
      to metastasize. Progression of tumor cells is always followed by cell composition
      and extracellular matrixcomponent alteration. Increased alpha-SMA expression and
      collagen alteration may predict the progressivity of ovarianneoplasms. Objective:
      The aim of this research was to analyse the characteristic of alpha-SMA and
      collagen in tumorcells and stroma of ovarian neoplasms. In this study, PCNA
      (proliferating cell nuclear antigen) expression was alsoinvestigated. Methods:
      Thirty samples were collected including serous, mucinous, endometrioid, and clear
      cell subtypes.The expression of alpha-SMA and PCNA were calculated in cells and
      stroma of ovarian tumors. Collagen was detectedusing Sirius Red staining and
      presented as area fraction. Results: The overexpressions of alpha-SMA in tumor
      cells wereonly detected in serous and clear cell ovarian carcinoma. The
      histoscore of alpha-SMA was higher in malignant than inbenign or borderline
      ovarian epithelial neoplasms (105.3+/-129.9 vs. 17.3+/-17.1, P=0.011; mean+/-SD).
      Oppositely, stromalalpha-SMA and collagen area fractions were higher in benign
      than in malignant tumors (27.2+/-6.6 vs 20.5+/-8.4, P=0.028;31.0+/-5.6 vs. 23.7+/
      6.4, P=0.04). The percentages of epithelial and stromal PCNA expressions were not
      significantlydifferent between benign and malignant tumors. Conclusion: Tumor
      cells of serous and clear cell ovarian carcinomaexhibit mesenchymal
      characteristic as shown by alpha-SMA positive expression. This expression might
      indicate that thesesubtypes were more aggressive. This research showed that
      collagen and alpha-SMA area fractions in stroma were higherin benign than in
      malignant neoplasms.

PMID- 28440974
TI  - Risk Estimation for Lung Cancer in Libya: Analysis Based on Standardized
      Morbidity Ratio, Poisson-Gamma Model, BYM Model and Mixture Model
AB  - Cancer is the most rapidly spreading disease in the world, especially in
      developing countries, including Libya. Cancerrepresents a significant burden on
      patients, families, and their societies. This disease can be controlled if
      detected early.Therefore, disease mapping has recently become an important method
      in the fields of public health research and diseaseepidemiology. The correct
      choice of statistical model is a very important step to producing a good map of a
      disease.Libya was selected to perform this work and to examine its geographical
      variation in the incidence of lung cancer. Theobjective of this paper is to
      estimate the relative risk for lung cancer. Four statistical models to estimate
      the relativerisk for lung cancer and population censuses of the study area for
      the time period 2006 to 2011 were used in this work.They are initially known as
      Standardized Morbidity Ratio, which is the most popular statistic, which used in
      the fieldof disease mapping, Poisson-gamma model, which is one of the earliest
      applications of Bayesian methodology, Besag,York and Mollie (BYM) model and
      Mixture model. As an initial step, this study begins by providing a review of
      allproposed models, which we then apply to lung cancer data in Libya. Maps,
      tables and graph, goodness-of-fit (GOF)were used to compare and present the
      preliminary results. This GOF is common in statistical modelling to comparefitted
      models. The main general results presented in this study show that the Poisson
      gamma model, BYM model, andMixture model can overcome the problem of the first
      model (SMR) when there is no observed lung cancer case incertain districts.
      Results show that the Mixture model is most robust and provides better relative
      risk estimates acrossa range of models.

PMID- 28440975
TI  - Follicular lymphoma: an Institutional Analysis
AB  - Background: Follicular lymphoma (FL) is second most common lymphoma in adult,
      constituted 20% of all lymphomacases in the west. There is limited information is
      available on FL from India. Methods: The clinico-pathological profile,treatment
      outcome and prognostic factors for survival were assessed retrospectively in 181
      patients of FL seen at ourcenter over a period of 17 years ( 1996-2012). Results:
      There were 120 males and 61 females. The median age was 51years (24-80 years).
      The common presenting features were lymphadenopathy 71%, fatigue 23% and fever
      20%. AnnArbor stage distribution was: stage I - 9%, stage II - 11%, stage III -22
      % and stage IV - 58%. Extra nodal involvementand bulky disease were present in
      22% and 19% patients respectively. Follicular Lymphoma International
      PrognosticIndex (FLIPI) 1 score : Low -25%, Intermediate-45% and high risk in 30%
      of cases. One forty five patients (80%)received treatment at presentation or
      during follow-up. Chemotherapeutic regimen used were: CHOP-45 , CVP
      51,chlorambucil and prednisolone -7 , BR ( bendamustine and rituximab)-12, RCHOP-
      14 RCVP - 7 and other regimenwere used in 5 cases. The overall response (ORR) and
      complete remission (CR) rates were 70% and 35% respectively.Median overall
      survival (OS) and event free survival (EFS) was 5.5 years and 2.5 years
      respectively, with medianfollow up period of 3.0 years. Grade 3 histology,
      failure to attain CR, low serum albumin, and high risk FLIPI weresignificantly
      associated with lower event free survival. High risk FLIPI (HR 1.46, 95% CI 1.03
      2.10, p=0.003) andfailure to attain CR (HR 2.64, CI 1.10-4.30, p=0.001) were
      predictors of poor OS. Conclusions: FL represents 9 % ofall lymphoma in adult.
      This is the largest data from single institute from India. Eighty percentage of
      patients presentedin stage III/IV disease. High risk FLIPI and failure to attain
      CR were important prognostic variables for OS.

PMID- 28440976
TI  - Diagnostic Value of the CareTM HPV Test in Screening for Cervical Intraepithelial
      Neoplasia Grade 2 or Worse
AB  - Background: Cervical cancer is the fourth leading cause of cancer death in women
      worldwide. Persistent infection witha high risk human papillomavirus (HR-HPV) is
      the main etiological factor, so that early early detection of HR-HPV isvery
      important. The aim of this study was to investigate the efficacy of CareTM HPV, a
      new method, as compared withPap smear, PCR, and biopsy for screening purposes.
      Material and Method: In this cross-sectional study, 200 sexuallyactive women
      aging from 25-50 years referred to the oncology clinic of Shahid Sodoughi Yazd
      Hospital in 2015 with avariety of cervix epithelial lesions or a need for
      colposcopy were enrolled. Results for CareTM HPV test (cervical), Papsmear, PCR,
      and biopsy were analyzed using SPSS 15 software and chi-square test, McNemar, and
      ROC curve analysis.Qualitative variables were compared using a Chi-square test.
      Results: CareTM HPV test sensitivity in detecting cervicalintraepithelial
      neoplasia grade II (CIN-II) and also positive and negative predictive values were
      higher as comparedto with other tests (p<0.05). The Pap smear test specificity
      was highest. There was no significant differences betweenCareTM HPV and PCR tests
      regarding detection of HPV-DNA in cases of CIN-II and worse (p>0.05). Conclusion:
      TheCareTM HPV test has high sensitivity and predictive values for detecting HPV
      infection, with higher efficacy than thePap smear test for tracking CIN-II.
      Therefore it may be recommended for use as a screening test in low-income areas.

PMID- 28440977
TI  - Low Re-infection Rate of Helicobacter pylori after Successful Eradication in
      Thailand: A 2 Years Study
AB  - Background: H. pylori is an important cause of chronic gastritis, peptic ulcers
      and gastric cancer. Re-infectionrates after successful eradication vary in
      different regions of the world but only limited studies have been performed
      inASEAN Countries to clarify this important issue. The present study was designed
      to evaluate the H. pylori re-infectionrate and predictors of re-infection in
      Thailand. Methods: We recruited patients with chronic gastritis after 1 and 2
      yearssuccessful H. pylori eradication from Thammasat University Hospital,
      Pathumthani (Central urban area) and Maesoddistrict, Tak (Northern rural area),
      Thailand. 13C-UBT was performed to evaluate re-infection status after cessationof
      PPI, H2 blocker and antibiotics for at least 4 weeks. Statistical analysis was
      performed using SPSS for WindowsVersion 22.0 (IBM Corp., Armonk, NY). Results: A
      total of 105 subjects were enrolled (40 M and 65F with a mean ageof 53.1 years).
      The overall re-infection rate was 6/105 (5.7%). The 1-year and 2-year H. pylori
      re-infection rates aftersuccessful eradication were only 5.1% (2/39) and 6.1%
      (4/66). 1-year and 2-year reinfection rates in urban areas were2/39 (5.1%) and
      1/26 (3.8%), while the 2-year reinfection rate in rural areas was 3/40 (7.5%).
      Location (urban vs ruralarea) and sex did not show any association with either 1
      year or 2-year H. pylori re-infection. With 2-year reinfection,the mean age of H.
      pylori re-infected patients was significantly higher than those who remained
      cured (63.0 years vs.51.6 years, p-value = 0.01). The annual H. pylori infection
      rate was 2.9%. Conclusions: 1-year and 2-year H. pylorire-infection rates after
      successful eradication in Thailand appear low in both rural and urban areas. H.
      pylori eradicationfor prevention of significant upper GI disease should be
      recommended and confirmation of successful eradication shouldbe the aim. Patients
      at higher risk such as the elderly should be monitored for possible risk of H.
      pylori re-infection.

PMID- 28440978
TI  - Methylation Status of P16Ink4a in Human Papillomavirus-Associated Cancer of Oral
      Cavity and Oropharynx in Northeastern Thailand
AB  - Background: Over-expression of p16INK4a protein is a biomarker for human
      papillomavirus (HPV)-associated cervicalcancer. However, absence of p16INK4a
      protein expression in HPV-associated cancer of the oral cavity and oropharynx
      hasbeen reported. Among a number of possible reasons for this is methylation,
      which is frequently noted in the promoterregion of p16INK4a and is associated
      with silencing of the gene and disease severity. Methods: We investigated
      therelationships between p16INK4a protein expression, HPV infection and
      methylation status of the p16INK4a promoter incancers of the oral cavity and
      oropharynx. Fifty-three formalin-fixed paraffin-embedded (FFPE) cancer tissue
      samplesfrom the oral cavity (49 cases) and oropharynx (4 cases) were studied.
      P16INK4a protein expression was determinedusing immunohistochemical staining
      (IHC). Additional oral tissues lacking squamous intraepithelial lesions
      (SILs),and cervical tissues with high-level SILs, were used as negative and
      positive controls, respectively. High-risk HPVinfection was detected using HPV
      E6/E7 mRNA in situ hybridization. Methylation status of the p16INK4a promoter
      wasinvestigated using sodium bisulfite treatment and methylation-specific PCR (MS
      PCR). Results: HPV infection wasfound in 40.8% (20/49) and 50.0% (2/4) of oral
      cavity and oropharynx cancers, respectively. Promoter methylationof p16INK4a
      occurred in 73.6 % of all cases and differed significantly in frequency between
      HPV-positive (90.9%,20/22) and HPV-negative (61.3%, 19/31) samples. Expression of
      p16INK4a was found in 35.8% (19/53) and commonlydetected in samples with p16INK4a
      unmethylation (79.5%). Interestingly, the silencing of p16INK4a (64.2%, 34/53)
      wassignificantly associated with methylation status (91.2%, 31/34), especially in
      HPV-infected samples in which thep16INK4a promoter was methylated (52.9%, 18/34).
      Conclusions: This result demonstrated high frequency of p16INK4apromoter
      methylation status in HPV-associated HNSCC subsets that could influence the
      silent p16INK4a expression andmight promote disease severity.

PMID- 28440979
TI  - [The training of healthcare personnel and the improvement in health care].
AB  - As part of its commitment to improve healthcare services persistently, the
      Instituto Mexicano del Seguro Social (IMSS) takes part in the constant training
      of its healthcare personnel, since the Institute knows that this has an impact on
      creating a virtuous circle of higher quality and giving cordial attention to
      patients. That is the reason why the Unidad de Educacion, Investigacion y
      Politicas en Salud has set up different programs, which offer diverse
      oportunities of study, always in line with the needs of the Institute.

PMID- 28440980
TI  - [Risk factors and clinical features of ectopic pregnancy].
AB  - BACKGROUND: Ectopic pregnancy (EP) is the most frequent cause of maternal death
      in the first trimester of pregnancy. The objective was to establish the clinical
      features and risk factors associated with EP. METHODS: Observational,
      retrospective, transversal and analytic case-control study. Two groups were
      included: the cases group (28 patients) and the control group (56 postpartum
      patients). Univariate and bivariate descriptive statistical analysis were carried
      out using the Pearson chi-square test, p < 0.05, with odds ratios (OR) and 95%
      confidence intervals (95% CI). RESULTS: Statistically significant values (OR)
      were: smoking: 18.33, history of EP: 11.96, IUD use: 11.9, abdominal surgery:
      5.87, being multigravid: 3.80, and having two or more sexual partners: 2. The
      most common clinical symptom was pelvic pain with 57.1% (16), right ruptured EP
      53.6%, tubal pregnancy 82.1% (23), unruptured EP 60.7% (17), hemoperitoneum 60.7%
      (17). Gestational age for EP was of 4-8 weeks (75%) and surgical treatment 96.4%.
      CONCLUSIONS: The frequency of EP found in our population was 1 in every 122 live
      births. Risk factors associated with ectopic pregnancy with statistically higher
      values were: smoking, being multigravid, having a clinical record of EP, IUD use
      before conception, abdominal surgery. The more frequent clinical characteristics
      were pelvic pain, right EP, tubal pregnancy, EP with no ruptures, hemoperitoneum
      < 750 ml, a gestational age between four and eight weeks.

PMID- 28440981
TI  - [Leading causes of death during the induction therapy in pediatric patients with
      acute lymphoblastic leukemia].
AB  - BACKGROUND: Leukemias are the leading cause of childhood cancer. In most
      developed countries 1-2% of patients die during remission induction; however, in
      developing countries, this figure is higher and the causes of death apparently
      vary among the populations studied. The aim was to determine the cause of death
      during remission induction in pediatric patients with acute lymphoblastic
      leukemia (ALL) in the hospital "Dr. Gaudencio Gonzalez Garza" of Centro Medico
      Nacional La Raza from January 1, 2009, to December 31, 2014. METHODS: A
      retrospective cohort study was carried out and a descriptive statistical analysis
      was performed. RESULTS: During the study period, a total of 463 patients with ALL
      were diagnosed, out of which 5.4% died (n = 25). Among the patients who died, 64%
      (n = 16) were female and 60% had high-risk clinical features at diagnosis. The
      main causes of death were septic shock and bleeding. CONCLUSIONS: Early mortality
      was five times higher than the one reported for developed countries, while the
      causes of death did not differ. Close monitoring is necessary to detect and
      promptly treat complications secondary to chemotherapy toxicity in Mexican
      pediatric patients with ALL.

PMID- 28440982
TI  - [Intelligence quotient loss in Mexican pottery artisan's children].
AB  - BACKGROUND: In Mexico, artisans frequently use lead oxide or greta in order to
      produce utensils, which are destined to preparation and storage of food and
      drinks. Additionally, the risk of lead poisoning of artisans and their families
      is greater than in general population, and within these families, children are
      the most susceptible to lead poisoning. The aim of this study was to estimate IQ
      loss in Mexican children from potter families exposed to lead. METHODS: Lead
      concentrations in soil were determined in 19 potter's homes that functioned as
      pottery workshops in seven Mexican states between 2009 and 2012. This information
      was used to estimate blood lead levels through the integrated exposure uptake
      biokinetic (IEUBK) model. The loss of IQ points was then estimated according to
      the Lanphear and Schwartz models. RESULTS: The mean lead concentration found in
      the workshops' soil was 1098.4 ppm. Blood lead levels estimated in children under
      8 years old were 26.4 ug/dL and the loss of IQ points comprised from 7.13 to 8.84
      points depending on the model. CONCLUSIONS: It is possible that 11 children from
      families of artisans in Mexico may be losing between 7.13 to 8.84 IQ points, due
      to lead exposure in their houses-workshops. This loss in IQ points could have
      important health, economic and social impacts.

PMID- 28440983
TI  - [Detection of cardiovascular risk in healthcare workers on the basis of WHO/JNC
      7/ATP III criteria].
AB  - BACKGROUND: Anthropometric and blood pressure measurements are significant
      parameters in the assessment of cardiovascular risk (CVR). The aim was to
      establish the distribution of clinical-anthropometric parameters in health care
      workers according to the criteria established by WHO/JNC 7/ATP III. METHODS:
      Observational, cross-sectional study in 350 workers of a general hospital.
      Definitions of anthropometric alterations were made considering the criteria
      established by WHO and the Asian ATP III, while altered blood pressure was
      defined by criteria JNC 7 and ATP III. RESULTS: The average age of workers was 34
      years. The prevalence of obesity, abdominal obesity, and impaired waist-hip ratio
      (WHR) was higher according to the ATP III criteria. The distribution of obesity
      prevailed in females, administrative personnel, and nursing according to WHO
      criteria, but there were no differences according to ATP III criteria. The WHR
      predominated in females and impaired blood pressure in males. 50% showed impaired
      capillary glucose. The number of anthropometric and clinical abnormalities, as
      well as its combinations, varied; most often it was found in one and three
      alterations with WHO and ATP III criteria, respectively. CONCLUSIONS: The
      prevalence of CVR factors in health workers is high, which is why we suggest to
      implement immediate action strategies to reduce its comorbidities and the
      institutional and personal costs related to these factors; we also encourage to
      apply the ATP criteria to decrease the subdiagnostic of CVR in this population.

PMID- 28440984
TI  - [FINDRISC Test: Relationship between cardiovascular risk parameters and scales in
      Spanish Mediterranean population].
AB  - BACKGROUND: The Finnish Diabetes Risk Score (FINDRISC) questionnaire has been
      used to assess the risk of type 2 diabetes and metabolic syndrome. The objetive
      was to assess the relationship between different scales related to cardiovascular
      risk and FINDRISC questionnaire. METHODS: Values of different anthropometric and
      clinical parameters (body mass index, waist circumference, waist to height ratio,
      blood pressure), analytical parameters (lipid profile, blood glucose) and scales
      related to cardiovascular risk (atherogenic index, metabolic syndrome, REGICOR,
      SCORE, heart age and vascular age) were determined on the basis of the value of
      the FINDRISC questionnaire. RESULTS: All analyzed parameters related to
      cardiovascular risk were getting worse at the same time that the value of the
      FINDRISC questionnaire increased. CONCLUSIONS: There is a close relationship
      between FINDRISC questionnaire values and those obtained in the different
      parameters by which cardiovascular risk was measured directly or indirectly.

PMID- 28440985
TI  - [Early neonatal sepsis and associated factors].
AB  - BACKGROUND: Early-onset neonatal sepsis (EONS) is an infectious disease of low
      incidence but high morbidity and mortality with severe consequences to the
      newborn prognosis. Identifying the associated factors related to EONS allows to
      start a timely treatment and to take preventive measures. METHODS: In this case
      and controls study we identified all the newborns (NB) with and without EONS
      (cases and controls), diagnosed through blood culture in a period of three years.
      We studied risk factors such as: low gestational age, gender, weight, maternal
      infections, and premature rupture of membranes. RESULTS: Our study consisted of
      27 cases and 36 controls, with a mean age of 32.43 and 33.19 weeks of gestation
      (WOG), respectively (p > 0.05). Of these, 22 and 29 of the cases and controls had
      a gestational age < 37 WOG, (p > 0.05). However, maternal infection (odds ratio
      [OR] 1.76), respiratory distress syndrome (OR 4.72), the need of resuscitation
      (OR 2.9), intubation (OR 5.1) and ventilation support (OR 2.6) were statistically
      different between both groups (p < 0.05). The most isolated microorganism was
      Staphylococcus coagulase negative (42.3%). CONCLUSIONS: Risk factors associated
      with EONS were maternal infection, the need of resuscitation, and intubation to
      ventilation support.

PMID- 28440986
TI  - [Prognostic factors of postoperative severe hyperglycemia after cardiac surgery
      in pediatric patients].
AB  - BACKGROUND: Patients who underwent surgery for congenital heart disease requiring
      cardiopulmonary bypass (CPB) have metabolic complications, like hyperglycemia,
      which is associated to a greater postoperative morbidity and mortality. Our
      objective was to identify predictors of severe postoperative hyperglycemia (>=
      200 mg/dL) in pediatric patients after cardiopulmonary bypass. METHODS: A case
      control study was conducted from January 1 to December 31, 2014. We included all
      pediatric patients undergoing cardiac surgery attended at postoperative care in a
      pediatric intensive care unit from a third level hospital. The dependent variable
      was severe postoperative hyperglycemia (>= 200 mg/dL). An unconditional logistic
      regression analysis was performed and confidence intervals of 95% (95% CI) were
      calculated to identify the most important and independent predictors associated
      with severe postoperative hyperglycemia. RESULTS: The frequency of severe
      postoperative hyperglycemia in our sample was 45.9%, being the most important and
      independent predictors the cyanotic heart disease (p = 0.04), postoperative serum
      lactate levels of more than 3 mmol/L (p = 0.001) and a level of deep hypothermia
      (< 25  degrees C) during perfusion (p = 0.01). The frequency of severe
      postoperative hyperglycemia was high in the studied population. CONCLUSIONS: It
      is important to carry out systematic monitoring of postoperative blood glucose in
      order to timely detect and treat these patients.

PMID- 28440987
TI  - [Tumors of the central nervous system].
AB  - Central nervous system (CNS) tumors constitute a heterogeneous group of neoplasms
      that share a considerable morbidity and mortality rate. Recent advances in the
      underlying oncogenic mechanisms of these tumors have led to new classification
      systems, which, in turn, allow for a better diagnostic approach and therapeutic
      planning. Most of these neoplasms occur sporadically and several risk factors
      have been found to be associated with their development, such as exposure to
      ionizing radiation or electromagnetic fields and the concomitant presence of
      conditions like diabetes, hypertension and Parkinson's disease. A relatively
      minor proportion of primary CNS tumors occur in the context of hereditary
      syndromes. The purpose of this review is to analyze the etiopathogenesis,
      clinical presentation, diagnosis and therapy of CNS tumors with particular
      emphasis in the putative risk factors mentioned above.

PMID- 28440988
TI  - [How safe is the recombinant human growth hormone?]
AB  - In this paper, several aspects related to the safety of the use of biosynthetic
      human growth hormone are reviewed. For example, its classification as a
      biosynthetic drug, the phases that need to be performed in Mexico to verify its
      safety (obtaining, purification, preclinical studies, clinical trials, and
      finally observational clinical studies), as well as the evidence that exists in
      relation to the association of intracranial hypertension, muscular events,
      scoliosis, slipped capital femoral epiphysis, obstructive sleep apnea,
      pancreatitis, alterations in cortisol, thyroid hormones alterations,
      cardiovascular disease, metabolic risk, mortality and cancer, adverse events not
      related to its use, and finally dosing and safety.

PMID- 28440989
TI  - [Diagnostic approach of erythroderma in the adult].
AB  - Erythroderma consists on erythema and scaling that covers more than 90% of the
      cutaneous surface. It has multiple causes and for the most common we can use the
      acronym PALM (psoriasis, atopic dermatitis, lymphoproliferative disease and
      medication). It is important to diagnose the cause in order to get a prognosis
      and a targeted treatment. In 30% of the cases the cause is not evident and the
      patient requires periodic assessment to rule out evolution to a
      lymphoproliferative disease. In many cases, erythroderma is a chronic disease but
      it can also be a life-threatening dermatologic urgency that requires
      hospitalization.

PMID- 28440990
TI  - [Duplicate publication].

PMID- 28440991
TI  - [Answer to comment "Duplicate publication"].

PMID- 28440992
TI  - [Autoimmune/inflammatory syndrome induced by adjuvants. A new clinical entity?]
AB  - Recently Shoenfeld and Agmon-Levin proposed a new clinical entity called
      autoimmune/inflammatory syndrome induced by adjuvants (ASIA), which includes four
      clinical entities called: 1) siliconosis, 2) Gulf War syndrome, 3) macrophage
      myofasciitis) and 4) post-vaccination phenomenon associated with adjuvants. They
      all have a common denominator: a prior exposure to immunoadjuvants, and, in
      addition, they also share several clinical criteria associated to chronic
      inflammation and autoimmune reactions. This proposal still needs to be validated
      by the scientific community, but nowadays is a topic of hot discussion in the
      literature and in various international conferences. In this revision article, we
      analyze the characteristics of this syndrome, the current mechanisms possibly
      involved in the pathogenesis, and the more recent reports regarding ASIA
      associated to vaccine and some foreign substances.

PMID- 28440993
TI  - [Training of institutional research networks as a strategy of improvement].
AB  - The Instituto Mexicano del Seguro Social (IMSS) through the Coordinacion de
      Investigacion en Salud (Health Research Council) has promoted a strong link
      between the generation of scientific knowledge and the clinical care through the
      program Redes Institucionales de Investigacion (Institutional Research Network
      Program), whose main aim is to promote and generate collaborative research
      between clinical, basic, epidemiologic, educational, economic and health services
      researchers, seeking direct benefits for patients, as well as to generate a
      positive impact on institutional processes. All of these research lines have
      focused on high-priority health issues in Mexico. The IMSS internal structure, as
      well as the sufficient health services coverage, allows the integration of
      researchers at the three levels of health care into these networks. A few years
      after their creation, these networks have already generated significant results,
      and these are currently applied in the institutional regulations in diseases that
      represent a high burden to health care. Two examples are the National Health Care
      Program for Patients with Acute Myocardial Infarction "Codigo Infarto", and the
      Early Detection Program on Chronic Kidney Disease; another result is the
      generation of multiple scientific publications, and the promotion of training of
      human resources in research from the same members of our Research Networks. There
      is no doubt that the Coordinacion de Investigacion en Salud advances steadily
      implementing the translational research, which will keep being fruitful to the
      benefit of our patients, and of our own institution.

PMID- 28440995
TI  - [The first clinical description of granulomatosis with polyangiitis (known before
      as Wegener's granulomatosis)].
AB  - Before 1950, cases of necrotizing vasculitis were commonly published in journals
      of pathology. Most of these cases were designated as polyarteritis nodosa. In
      1952, the pathologist Pearl Zeek critically reviewed and summarized the
      literature dealing with polyarteritis nodosa and first grouped the different
      types of necrotizing vasculitis. But she omitted some types of not well
      characterized vasculitis, among them granulomatosis with polyangiitis (Wegener's
      granulomatosis).

PMID- 28440996
TI  - [Quality dimensions focused on the healthcare protocol Infarction Code (Codigo
      Infarto)].
AB  - The Codigo Infarto (Infarction Code) strategy is part of the comprehensive care
      program "A Todo Corazon" (To All Heart), whose aim is to reinforce the prevention
      and health care of cardiovascular diseases. Mexico faces a big challenge, since
      it is the country with greater mortality secondary to acute myocardial infarction
      (AMI) in the first 30 days in patients of 45 years or older (28% compared with
      7.9% of the average). In addition, Mexico's population has a high prevalence of
      risk factors (hypertension, diabetes, tobacco use, dyslipidemias, overweight, and
      obesity). It is for these reasons that 18 months ago the Instituto Mexicano del
      Seguro Social (IMSS) implemented the first care protocol for patients with AMI,
      called Codigo Infarto, whose main aim is to guarantee the diagnosis and treatment
      of patients with AMI, so that they can receive, once they are admitted at IMSS
      emergency rooms, primary angioplasty in less than 90 minutes, or fibrinolytic
      therapy in less than 30 minutes. The quality focus in the Codigo Infarto strategy
      has six main dimensions: security, effectiveness, its focus on the patient,
      opportune, efficient, and [it offers] equitable [treatment]. The implementation
      of Codigo Infarto in IMSS is the first institutional strategy to face the leading
      cause of death in our country and it has produced up until now very encouraging
      results.

PMID- 28440997
TI  - [Neisseria meningitidis: A clinical case with multi-organ affection].
AB  - Neisseria meningitidis (Nm) is an agent feared for decades in the medical field
      due to its important morbidity and mortality. Ironically between 10 and 15% of
      the population will be asymptomatic carriers of this germ, which will also be
      ready to activate and manifest itself as a sickness at the right moment. We
      present the case of a nine-year-old girl who arrived at the Pediatric Emergency
      Service (to the Hospital General Region number 35, in Ciudad Juarez, Chihuahua)
      with the disease in multiple organs, where the Nm was isolated in the
      cerebrospinal fluid and in skin injuries, displaying three serotypes of Nm. Until
      today this germ still displays sensibility to penicillin use. Luckily the patient
      is still alive and without any neurological damage.

PMID- 28440998
TI  - [Extranodal NK-T-cell lymphoma, nasal type in granulomatosis with polyangiitis. A
      case report].
AB  - BACKGROUND: Granulomatosis with polyangiitis (GP) is a systemic necrotizing
      vasculitis with multi-organ involvement that primarily affects the respiratory
      tract and the kidneys. Fever in these patients is an indicator of activity;
      however, if it arises in isolation, the physician should exclude other causes.
      CLINICAL CASE: Male patient admitted due to an unexplained fever and weight loss;
      it was diagnosed GP by a history of pauci-immune glomerulonephritis, fixed
      pulmonary nodules and chronic sinusitis of four years of evolution; however, the
      fever persisted despite treatment and in the absence of infection. It was
      performed an oropharynx lesion biopsy and the diagnosis was extranodal NK-T-cell
      lymphoma, nasal type, and positive for CD56 and granzyme. CONCLUSION: Extranodal
      NK-T-cell lymphoma, nasal type is a rare entity, of poor prognosis, that should
      be considered as a diagnosis in patients with GP unresponsive to steroid. That is
      the reason why biopsy of the lesion and immunohistochemistry are required.

PMID- 28441000
TI  - [Presentation: Mexican Asthma Guidelines 2017].

PMID- 28440999
TI  - [Epistemic injustice during the medical education process in the hospital
      context].
AB  - BACKGROUND: The educational model adopted by the Universidad Nacional Autonoma de
      Mexico (UNAM) Faculty of Medicine is constructivist; it is a model based on
      competence development. It aims to provide learning environments that incorporate
      real activities (it helps the students to develop social negotiation skills, as
      part of their integral learning; it encourages them to take a critical and
      reflexive approach; and it is also a student-centered model). However, many
      challenges arise when this model is implemented in the context of hospital
      environments. Therefore, our aim was to analyse the hospital as an hermeneutical
      community and as a power relations scenario, contrary to the constructivist
      model. METHODS: In the analysis of a conflict between a chief of a medical
      department and an undergraduated medical intern, we use Miranda Fricker's
      categories discriminatory epistemic injustice, and testimonial injustice, as well
      as Foucault's power relationships and knowledge. RESULTS: The program
      implementation is placed in the context of power relations and different
      disciplinary methods that could affect the training process of the students,
      whose educational background belongs to the constructivist model. This in part is
      due to the existence of informal normative structures that are hidden in the
      process of medical knowledge construction at the hospital scenario. CONCLUSION:
      Practices of epistemic discriminatory injustice in the hospital environment
      increase vulnerability conditions for medical students in their education
      process.

PMID- 28441002
TI  - Correction to Assessing the Methane Emissions from Natural Gas-Fired Power Plants
      and Oil Refineries.

PMID- 28441001
TI  - [Mexican Asthma Guidelines: GUIMA 2017].
AB  - BACKGROUND: The need for a national guideline, with a broad basis among
      specialists and primary care physicians was felt in Mexico, to try unifying
      asthma management. As several high-quality asthma guidelines exist worldwide, it
      was decided to select the best three for transculturation. METHODS: Following the
      internationally recommended methodology for guideline transculturation, ADAPTE, a
      literature search for asthma guidelines, published 1-1-2007 through 31-12-2015
      was conducted. AGREE-II evaluations yielded 3/40 most suitable for
      transculturation. Their compound evidence was fused with local reality, patient
      preference, cost and safety considerations to draft the guideline document.
      Subsequently, this was adjusted by physicians from 12 national medical societies
      in several rounds of a Delphi process and 3 face-to-face meetings to reach the
      final version. RESULTS: Evidence was fused from British Thoracic Society Asthma
      Guideline 2014, Global Initiative on Asthma 2015, and Guia Espanola del Manejo
      del Asma 2015 (2016 updates included). After 3 Delphi-rounds we developed an
      evidence-based document taking into account patient characteristics, including
      age, treatment costs and safety and best locally available medication.
      CONCLUSIONS: In cooperation pulmonologists, allergists, ENT physicians,
      paediatricians and GPs were able to develop an evidence-based document for the
      prevention, diagnosis and treatment of asthma and its exacerbations in Mexico.

PMID- 28441003
TI  - Chemical Interaction-Guided, Metal-Free Growth of Large-Area Hexagonal Boron
      Nitride on Silicon-Based Substrates.
AB  - Hexagonal boron nitride (h-BN) is an ideal platform for interfacing with two
      dimensional (2D) nanomaterials to reduce carrier scattering for high-quality 2D
      electronics. However, scalable, transfer-free growth of hexagonal boron nitride
      (h-BN) remains a challenge. Currently, h-BN-based 2D heterostructures require
      exfoliation or chemical transfer of h-BN grown on metals resulting in small areas
      or significant interfacial impurities. Here, we demonstrate a surface-chemistry
      influenced transfer-free growth of large-area, uniform, and smooth h-BN directly
      on silicon (Si)-based substrates, including Si, silicon nitride (Si3N4), and
      silicon dioxide (SiO2), via low-pressure chemical vapor deposition. The growth
      rates increase with substrate electronegativity, Si < Si3N4 < SiO2, consistent
      with the adsorption rates calculated for the precursor molecules via atomistic
      molecular dynamics simulations. Under graphene with high grain density, this h-BN
      film acts as a polymer-free, planar-dielectric interface increasing carrier
      mobility by 3.5-fold attributed to reduced surface roughness and charged
      impurities. This single-step, chemical interaction guided, metal-free growth
      mechanism of h-BN for graphene heterostructures establishes a potential pathway
      for the design of complex and integrated 2D-heterostructured circuitry.

PMID- 28441004
TI  - Insights into the Mechanisms by Which Clostridial Neurotoxins Discriminate
      between Gangliosides.
AB  - Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the causative
      agents of the paralytic diseases botulism and tetanus, respectively. Entry of
      toxins into neurons is mediated through initial interactions with gangliosides,
      followed by binding to a protein co-receptor. Herein, we aimed to understand the
      mechanism through which individual neurotoxins recognize the carbohydrate motif
      of gangliosides. Using cell-based and in vitro binding assays, in conjunction
      with structure-driven site-directed mutagenesis, a conserved hydrophobic residue
      within the BoNTs that contributes to both affinity and specificity toward Sia5
      containing gangliosides was identified. We demonstrate that targeted mutations
      within the Sia5 binding pocket result in the generation of neurotoxins that
      either bind and enter cells more efficiently (BoNT/A1 and BoNT/B) or display
      altered ganglioside binding specificity (TeNT). These data support a model in
      which recognition of Sia5 is largely driven by hydrophobic interactions between
      the sugar and the Sia5 binding site.

PMID- 28441005
TI  - Plasma-Activated Copper Nanocube Catalysts for Efficient Carbon Dioxide
      Electroreduction to Hydrocarbons and Alcohols.
AB  - Carbon dioxide electroreduction to chemicals and fuels powered by renewable
      energy sources is considered a promising path to address climate change and
      energy storage needs. We have developed highly active and selective copper (Cu)
      nanocube catalysts with tunable Cu(100) facet and oxygen/chlorine ion content by
      low-pressure plasma pretreatments. These catalysts display lower overpotentials
      and higher ethylene, ethanol, and n-propanol selectivity, resulting in a maximum
      Faradaic efficiency (FE) of ~73% for C2 and C3 products. Scanning electron
      microscopy and energy-dispersive X-ray spectroscopy in combination with quasi-in
      situ X-ray photoelectron spectroscopy revealed that the catalyst shape, ion
      content, and ion stability under electrochemical reaction conditions can be
      systematically tuned through plasma treatments. Our results demonstrate that the
      presence of oxygen species in surface and subsurface regions of the nanocube
      catalysts is key for achieving high activity and hydrocarbon/alcohol selectivity,
      even more important than the presence of Cu(100) facets.

PMID- 28441006
TI  - Ionic Gel Paper with Long-Term Bendable Electrical Robustness for Use in Flexible
      Electroluminescent Devices.
AB  - Conductive paper has low-cost, lightweight, sustainability, easy scale-up, and
      tailorable advantages, allowing for its promising potential in flexible
      electronics, such as bendable supercapacitors, solar cells, electromagnetic
      shields, and actuators. Ionic gels, exhibiting a lower Young's modulus together
      with facile manufacturing, can fully serve as the conductive component to prepare
      conductive paper. Herein we report a low-cost (~1.3 dollars/m2), continuous, and
      high-throughput (up to ~30 m/min) fabrication of reliable and long-term (stable
      for more than two months) conductive paper. As-prepared conductive paper shows a
      high electrical durability with negligible bending-recovering signal changes over
      5000 cycles. Using this ionic gel paper (IGP) as a key component, we build a
      variety of proof-of-principle demonstrations to show the capacity of IGP in
      constructing flexible electroluminescent devices with diverse patterns, including
      a square, an alphabetic string, and a laughing face. Our methodology has the
      potential to open a new powerful route to fabricate bendable conductive paper for
      a myriad of applications in future flexible electronics.

PMID- 28441007
TI  - Rough Structure of Electrodeposition as a Template for an Ultrarobust Self
      Cleaning Surface.
AB  - Superhydrophobic surfaces with self-cleaning properties have been developed based
      on roughness on the micro- and nanometer scales and low-energy surfaces. However,
      such surfaces are fragile and stop functioning when exposed to oil. Addressing
      these challenges, here we show an ultrarobust self-cleaning surface fabricated by
      a process of metal electrodeposition of a rough structure that is subsequently
      coated with fluorinated metal-oxide nanoparticles. Scanning electron microscopy,
      Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X
      ray diffraction were employed to characterize the surfaces. The micro- and
      nanoscale roughness jointly with the low surface energy imparted by the
      fluorinated nanoparticles yielded surfaces with water contact angle of 164.1
      degrees  and a sliding angle of 3.2 degrees . Most interestingly, the surface
      exhibits fascinating mechanical stability after finger-wipe, knife-scratch, sand
      abrasion, and sandpaper abrasion tests. It is found that the surface with
      superamphiphobic properties has excellent repellency toward common corrosive
      liquids and low-surface-energy substances. Amazingly, the surface exhibited
      excellent self-cleaning ability and remained intact even after its top layer was
      exposed to 50 abrasion cycles with sandpaper and oil contamination. It is
      believed that this simple, unique, and practical method can provide new
      approaches for effectively solving the stability issue of superhydrophobic
      surfaces and could extend to a variety of metallic materials.

PMID- 28441008
TI  - Simultaneous Detection of Dual Prostate Specific Antigens Using Surface-Enhanced
      Raman Scattering-Based Immunoassay for Accurate Diagnosis of Prostate Cancer.
AB  - Accurate analysis of specific biomarkers in clinical serum is essential for early
      diagnosis and treatment of cancer. Here, a surface-enhanced Raman scattering
      (SERS)-based immunoassay, using magnetic beads and SERS nano tags, was developed
      for the determination of free to total (f/t) prostate specific antigen (PSA)
      ratio to improve the diagnostic performance of prostate cancer. To assess the
      clinical applicability of the proposed method, SERS-based assays for the
      simultaneous detection of dual PSA markers, free PSA (f-PSA) and complexed PSA (c
      PSA), were performed for clinical samples in the gray zone between 4.0 and 10.0
      ng/mL. Our assay results for f/t PSA ratio showed a good linear correlation with
      those measured using the electrochemiluminescence (ECL) system installed in the
      clinical laboratory of the University Hospital. In addition, the simultaneous
      assay provided better precision than parallel assays for the detection of f-PSA
      and c-PSA in 13 clinical serum samples. Therefore, our SERS-based assay for
      simultaneous detection of dual PSA markers in clinical fluids has strong
      potential for application in the accurate diagnosis of prostate cancer.

PMID- 28441009
TI  - Bisazide Cyanine Dyes as Fluorogenic Probes for Bis-Cyclooctynylated Peptide Tags
      and as Fluorogenic Cross-Linkers of Cyclooctynylated Proteins.
AB  - Herein we present the synthesis and fluorogenic characterization of a series of
      double-quenched bisazide cyanine probes with emission maxima between 565 and 580
      nm that can participate in covalent, two-point binding bioorthogonal tagging
      schemes in combination with bis-cyclooctynylated peptides. Compared to other
      fluorogenic cyanines, these double-quenched systems showed remarkable
      fluorescence intensity increase upon formation of cyclic dye-peptide conjugates.
      Furthermore, we also demonstrated that these bisazides are useful fluorogenic
      cross-linking platforms that are able to form a covalent linkage between
      monocyclooctynylated proteins.

PMID- 28441010
TI  - Instrumental Setup for Simultaneous Total and Speciation Analysis of Volatile
      Arsenic Compounds in Gas and Liquefied Gas Samples.
AB  - Although analysis of metals and metalloids, such as arsenic, is widely spread in
      many different fields, their analysis in gas and liquefied gas samples is still a
      challenge. A new GC-ICP-MS set up has been developed for their simultaneous total
      and speciation analysis in gas and liquefied gas samples without the need of a
      preconcentration step. An arsine in nitrogen standard was used for optimization
      and evaluation of the system. Good linearity and detection limits in the very low
      ppt level for both total and speciation analyses were found. Liquefied butane
      pressurized under nitrogen and doped with arsine and a propylene real sample from
      a cracker plant were analyzed using both external calibration and standard
      additions methods. The good match between both quantifying approaches
      demonstrated almost negligible matrix effects, even for the total analysis.
      Application of the approach to check repartition of volatile elements or species
      between gas and liquid phases was performed in the real propylene sample.
      Finally, its potential applicability for the simultaneous total and speciation
      analysis of other elements, such as Hg, was also proved.

PMID- 28441011
TI  - Synthesis, Characterization, and DFT Analysis of Bis-Terpyridyl-Based Molecular
      Cobalt Complexes.
AB  - Terpyridine ligands are widely used in chemistry and material sciences owing to
      their ability to form stable molecular complexes with a large variety of metal
      ions. In that context, variations of the substituents on the terpyridine ligand
      allow modulation of the material properties. Applying the Stille cross-coupling
      reaction, we prepared with good yields a new series of terpyridine ligands
      possessing quinoline-type moieties in ortho, meta, and para positions and
      dimethylamino substituents at central or distal positions. The corresponding
      cobalt(II) complexes were synthesized and fully characterized by elemental
      analysis, single-crystal X-ray crystallography, mass spectrometry, and UV-vis, 1H
      NMR, and Fourier transform infrared (FT-IR) spectroscopy as well as by cyclic
      voltammetry (CV). Density functional theory (DFT) calculations were performed to
      investigate the electronic structure of all the Co(II) bis-terpyridyl molecular
      complexes. In this work, we show that terpyridine ligand functionalization allows
      tuning the redox potentials of the Co(III)/Co(II), Co(II)/Co(I), and Co(I)/Co(I)
      (tpy)*- couples over a 1 V range.

PMID- 28441012
TI  - RGB-Switchable Porous Electrospun Nanofiber Chemoprobe-Filter Prepared from
      Multifunctional Copolymers for Versatile Sensing of pH and Heavy Metals.
AB  - Novel red-green-blue (RGB) switchable probes based on fluorescent porous
      electrospun (ES) nanofibers exhibiting high sensitivity to pH and mercury ions
      (Hg2+) were prepared with one type of copolymer (poly(methyl methacrylatete-co
      1,8-naphthalimide derivatives-co-rhodamine derivative); poly(MMA-co-BNPTU-co
      RhBAM)) by using a single-capillary spinneret. The MMA, BNPTU, and RhBAM moieties
      were designed to (i) permit formation of porous fibers, (ii) fluoresce for Hg2+
      detection, and (iii) fluoresce for pH, respectively. The fluorescence emission of
      BNPTU (fluorescence resonance energy transfer (FRET) donor) changed from green to
      blue as it detected Hg2+. The fluorescence emission of RhBAM (FRET acceptor) was
      highly selective for pH, changing from nonfluorescent (pH 7) to exhibiting strong
      red fluorescence (pH 2). The full-color emission of the ES nanofibers included
      green, red, blue, purple, and white depending on the particular pH and Hg2+
      concentration combination of the solution. The porous ES nanofibers with 30 nm
      pores were fabricated using hydrophobic MMA, low-boiling-point solvent, and at a
      high relative humidity (80%). These porous ES nanofibers had a higher surface-to
      volume ratio than did the corresponding thin films, which enhanced their
      performance. The present study demonstrated that the FRET-based full-color
      fluorescence porous nanofibrous membranes, which exhibit on-off switching and can
      be used as naked eye probes, have potential for application in water purification
      sensing filters.

PMID- 28441014
TI  - Chemistry-Inspired Adaptable Framework Structures.
AB  - Adaptable crystalline frameworks are important in modern solid-state chemistry as
      they are able to accommodate a wide range of elements, oxidation states, and
      stoichiometries. Owing to this ability, such adaptable framework structures are
      emerging as the prototypes for technologically important advanced functional
      materials. In this Account, the idea of cosubstitution is explored as a useful
      "pairing" concept that can potentially lead to the creation of many new members
      of one particular framework structure. Cosubstitution as practiced is the
      simultaneous replacement of two or more cations, anions, complex anions, other
      fundamental building units, or vacancies. Although the overall sum of the
      oxidation states is constant, each component is not necessarily isovalent. This
      methodology is typically inspired by either mineral-type structural prototypes
      found in nature or those discovered in the laboratory. Either path leads to the
      appearance of new phases and the discovery of new materials. In addition, the
      chemical cosubstitution approach can be successfully adopted to improve physical
      properties associated with structures. This Account is structured as follows:
      first, we illustrate the significance and background of chemical cosubstitution
      by reviewing mineral-inspired structures, such as perovskite and lyonsite, and
      the structural unit discovered in some selected solid state compounds. With time,
      the number of lyonsite related phases should rival or even surpass the perovskite
      family. Several members of the lyonsite-type have been identified as Li-ion
      conductors and photocatalysts. There is also a noncentrosymmetric structure-type,
      and therefore the other properties associated with the loss of inversion symmetry
      should be anticipated. Next, we illustrate recent advances in the synthesis of
      the new cosubstituted solid state materials from our two groups including (1)
      nonlinear optical materials, (2) luminescent materials, (3) transparent
      conducting oxides, and (4) photocatalyst and photovoltaic materials. We emphasize
      that a concerted and rigorous theoretical and experimental approach will be
      required to define thermodynamic stability of the complex cosubstitution
      chemistries, structures, and properties that are yet unknown. We conclude by
      summarizing the topic and suggesting other possible adaptable framework
      structures where cosubstitution can be expected.

PMID- 28441013
TI  - Cytotoxicity of Pyrazine-Based Cyclometalated (C^Npz^C)Au(III) Carbene Complexes:
      Impact of the Nature of the Ancillary Ligand on the Biological Properties.
AB  - The synthesis of a series of cyclometalated gold(III) complexes supported by
      pyrazine-based (C^N^C)-type pincer ligands is reported, including the crystal
      structure of a cationic example. The compounds provide a new platform for the
      study of antiproliferative properties of gold(III) complexes. Seven complexes
      were tested: the neutral series (C^Npz^C)AuX [X = Cl (1), 6-thioguanine (4),
      C=CPh (5), SPh (6)] and an ionic series that included the N-methyl complex
      [(C^NpzMe^C)AuCl]BF4 (7) and the N-heterocyclic carbene complexes [(C^Npz^C)AuL]+
      with L = 1,3-dimethylbenzimidazol-2-ylidene (2) or 1,3,7,9-tetramethylxanthin-8
      ylidene (3). Tests against human leukemia cells identified 1, 2, 3, and 4 as
      particularly promising, whereas protecting the noncoordinated N atom on the
      pyrazine ring by methylation (as in 7) reduced the cytotoxicity. Complex 2 proved
      to be the most effective of the entire series against the HL60 leukemia, MCF-7
      breast cancer, and A549 lung cancer cell lines, with IC50 values down to
      submicromolar levels, associated with a lower toxicity toward healthy human lung
      fibroblast cells. The benzimidazolylidene complex 2 accumulated more effectively
      in human lung cancer cells than its caffeine-based analogue 3 and the gold(III)
      chloride 1. Compound 2 proved to be unaffected by glutathione under physiological
      conditions for periods of up to 6 days and stabilizes the DNA G-quadruplex and i
      motif structures; the latter is the first such report for gold compounds. We also
      show the first evidence of inhibition of MDM2-p53 protein-protein interactions by
      a gold-based compound and identified the binding mode of the compound with MDM2
      using saturation transfer difference NMR spectroscopy combined with docking
      calculations.

PMID- 28441015
TI  - "Bottom-up" Construction of Multi-Polyprodrug-Arm Hyperbranched Amphiphiles for
      Cancer Therapy.
AB  - Despite the great advantages of polymer-drug conjugates (PDC) in cancer therapy,
      control of the drug loading site and degree via a facile approach remains a great
      challenge. Herein, by combining the controllability of the "bottom-up" strategy
      and the stability of multiarm hyperbranched amphiphiles, we have developed novel
      multi-polyprodrug-arm hyperbranched amphiphiles (H40-star-(PHCPTMA-b-PMPC), hPCM)
      via reversible addition-fragmentation chain transfer (RAFT) polymerization for
      cancer therapy. The hPCM was constructed via two-step polymerization of an acid
      labile prodrug monomer and a zwitterionic monomer, respectively. By using an H40
      macroRAFT agent, 10-hydroxycamptothecine (HCPT) prodrug monomers were directly
      polymerized via the "bottom-up" strategy as a polyprodrug-arm inner-shell of hPCM
      with homogeneous drug distribution. The drug loading content can be facilely
      tuned through variation of the feed ratio of HCPTMA/H40 macroRAFT agent. Finally,
      the poly-zwitterionic hydrophilic outer-shell of hPCM was formed by RAFT
      polymerization of zwitterionic monomer to ensure preferable biocompatibility. By
      dissolving in dilute solution, unimolecular micelles of hPCM can be obtained,
      which endow desirable stability for the micelles. The effective cellular
      internalization, extended blood retention time, considerable accumulation in
      tumor tissue, and excellent anticancer activity of the hPCM micelles have been
      evaluated both in vitro and in vivo. This novel multi-polyprodrug-arm
      hyperbranched amphiphile constructed via the "bottom-up" strategy may open up new
      horizons for exploring next-generation PDC-based drug delivery systems.

PMID- 28441016
TI  - Optimization of the Synthesis of Flavone-Amino Acid and Flavone-Dipeptide Hybrids
      via Buchwald-Hartwig Reaction.
AB  - The article describes the development of Buchwald-Hartwig amination of different
      bromoflavones with amino acid and peptide derivatives as nitrogen source giving
      unique structures. The previously observed racemization, which occurred during
      the synthesis of flavone-amino acid hybrids, was successfully prevented in most
      cases. The biological assays of these novel structures showed cytotoxic effects
      on different cancer cell lines.

PMID- 28441017
TI  - Equilibration of Micelle-Polyelectrolyte Complexes: Mechanistic Differences
      between Static and Annealed Charge Distributions.
AB  - The role of charge density and charge annealing in polyelectrolyte complexation
      was investigated through systematic comparison of two micelle-polyelectrolyte
      systems. First, poly(dimethylaminoethyl methacrylate)-block-poly(styrene)
      (PDMAEMA-b-PS) micelles were complexed with poly(styrenesulfonate) (PSS) at pH
      values above and below the pKa of PDMAEMA to investigate the role of charge
      annealing in the complexation process. Second, complexes of poly(DMAEMA-stat
      oligo(ethylene glycol) methyl ether methacrylate)-block-poly(styrene) (P(DMAEMA
      stat-OEGMA)-b-PS) micelles with the same PSS at low pH were used to investigate
      how the complexation process differs when the charged sites are in fixed
      positions along the polymer chains. Characterization by turbidimetric titration,
      dynamic light scattering, and cryogenic transmission electron microscopy reveals
      that whether or not the charge distribution can rearrange during the complexation
      process significantly affects the structure and stability of the complexes. In
      complexes of PDMAEMA-b-PS micelles at elevated pH, in which the charge
      distributions can anneal, the charge sites redistribute along the corona chains
      upon complexation to favor more fully ion-paired configurations. This promotes
      rapid rearrangement to single-micelle species when the micelles are in excess but
      traps complexes formed with PSS in excess. In complexes with static charge
      distributions introduced by copolymerization of DMAEMA with neutral OEGMA
      monomers, on the other hand, the opposite is true: in this case, reducing the
      charge density promotes rearrangement to single-micelle complexes only when the
      polyanion is in excess. Molecular dynamics simulations show that disruption of
      the charge density in the corona brush reduces the barrier to rearrangement of
      individual ion pairs, suggesting that the inability of the brush to rearrange to
      form fully ion-paired complexes fundamentally alters the kinetics of complex
      formation and equilibration.

PMID- 28441018
TI  - Correction to The Silicon Version of Phosphine Chalcogenides: Synthesis and
      Bonding Analysis of Stabilized Heavy Silaaldehydes.

PMID- 28441019
TI  - Catalytic, Enantioselective beta-Protonation through a Cooperative Activation
      Strategy.
AB  - The NHC-catalyzed transformation of unsaturated aldehydes into saturated esters
      through an organocatalytic homoenolate process has been thoroughly studied.
      Leveraging a unique "Umpolung"-mediated beta-protonation, this process has
      evolved from a test bed for homoenolate reactivity to a broader platform for
      asymmetric catalysis. Inspired by our success in using the beta-protonation
      process to generate enals from ynals with good E/Z selectivity, our early studies
      found that an asymmetric variation of this reaction was not only feasible, but
      also adaptable to a kinetic resolution of secondary alcohols through NHC
      catalyzed acylation. In-depth analysis of this process determined that careful
      catalyst and solvent pairing is critical for optimal yield and selectivity;
      proper choice of nonpolar solvent provided improved yield through suppression of
      an oxidative side reaction, while employment of a cooperative catalytic approach
      through inclusion of a hydrogen bond donor cocatalyst significantly improved
      enantioselectivity.

PMID- 28441020
TI  - General C-H Arylation Strategy for the Synthesis of Tunable Visible Light
      Emitting Benzo[a]imidazo[2,1,5-c,d]indolizine Fluorophores.
AB  - Herein we report the discovery of the benzo[a]imidazo[2,1,5-c,d]indolizine motif
      displaying tunable emission covering most of the visible spectrum. The polycyclic
      core is obtained from readily available amides via a chemoselective process
      involving Tf2O-mediated amide cyclodehydration, followed by intramolecular C-H
      arylation. Additionally, these fluorescent heterocycles are easily functionalized
      using electrophilic reagents, enabling divergent access to varied substitution.
      The effects of said substitution on the compounds' photophysical properties were
      rationalized by density functional theory calculations. For some compounds,
      emission wavelengths are directly correlated to the substituent's Hammett
      constants. Easily introduced nonconjugated reactive functional groups allow the
      labeling of biomolecules without modification of emissive properties. This work
      provides a straightforward platform for the synthesis of new moderately bright
      fluorescent dyes remarkable for their chemical stability, predictability, and
      unusually high excitation-emission differential.

PMID- 28441021
TI  - Photophysical and Electroluminescent Properties of PtAg2 Acetylide Complexes
      Supported with meso- and rac-Tetraphosphine.
AB  - 1,2-Bis[[(diphenylphosphino)methyl](phenyl)phosphino]ethane (dpmppe) was prepared
      as a new tetraphosphine, and the corresponding rac and meso stereoisomers were
      successfully separated in view of their solubility difference in acetone. The
      substitution of PPh3 into Pt(PPh3)2(C=CR)2 (R = aryl) with rac- or meso-dpmppe
      gives Pt(rac-dpmppe)(C=CR)2 or Pt(meso-dpmppe)(C=CR)2, respectively. Using Pt(rac
      dpmppe)(C=CR)2 or Pt(meso-dpmppe)(C=CR)2 as a precursor, PtAg2 heterotrinuclear
      cluster complexes were synthesized and characterized by X-ray crystallography.
      Depending on the conformations of tetraphosphine, the structures of PtAg2
      complexes supported with rac- and meso-dpmppe are quite different. The higher
      molecular rigidity of rac-dpmppe-supported PtAg2 complexes results in stronger
      phosphorescent emission than that of PtAg2 species with meso-dpmppe. The high
      phosphorescent quantum yields (as high as 90.5%) in doping films warrant these
      PtAg2 complexes as excellent phosphorescent dopants in organic light-emitting
      diodes (OLEDs). The peak current and external quantum efficiencies in solution
      processed OLEDs are 61.0 cd A-1 and 18.1%, respectively. Electroluminescence was
      elaborately modulated by modifying the substituent in aromatic acetylide and the
      conformations in tetraphosphine so as to achieve cyan, green, green-yellow,
      yellow, and orange-red emission.

PMID- 28441022
TI  - Low-Valent Lead Hydride and Its Extreme Low-Field 1H NMR Chemical Shift.
AB  - Although hydrides of the group 14 elements are well-known as versatile starting
      materials in many chemical transformations, a hydride of lead in oxidation state
      II is so far unknown. In this work, we finally complete the jigsaw puzzle by
      reporting the isolation of the first low valent organolead hydride. The
      thermolabile dimeric organolead hydride was synthesized at low temperature and
      features a hydride 1H NMR signal (in solution 35.61 ppm; in the solid state 31.1
      ppm) at the lowest field observed so far for a diamagnetic compound in agreement
      with quantum chemical predictions.

PMID- 28441023
TI  - Hydrophobic Nanoparticles Modify the Thermal Release Behavior of Liposomes.
AB  - Understanding the effect of embedded nanoparticles on the characteristics and
      behavior of lipid bilayers is critical to the development of lipid-nanoparticle
      assemblies (LNAs) for biomedical applications. In this work we investigate the
      effect of hydrophobic nanoparticle size and concentration on liposomal thermal
      release behavior. Decorated LNAs (D-LNAs) were formed by embedding 2 nm (GNP2)
      and 4 nm (GNP4) dodecanethiol-capped gold nanoparticles into DPPC liposomes at
      lipid to nanoparticle ratios (L:N) of 25,000:1, 10,000:1, and 5,000:1. D-LNA
      structure was investigated by cryogenic transmission electron microscopy, and
      lipid bilayer permeability and phase behavior were investigated based on the
      leakage of a model drug, carboxyfluorescein, and by differential scanning
      calorimetry, respectively. The presence of bilayer nanoparticles caused changes
      in the lipid bilayer release and phase behavior compared to pure lipid controls
      at very low nanoparticle to bilayer volume fractions (0.3%-4.6%). Arrhenius plots
      of the thermal leakage show that GNP2 led to greater increases in the leakage
      energy barrier compared to GNP4, consistent with GNP4 causing greater bilayer
      disruption due to their size relative to the bilayer thickness. Embedding
      hydrophobic nanoparticles as permeability modifiers is a unique approach to
      controlling liposomal leakage based on nanoparticle size and concentration.

PMID- 28441024
TI  - Stereoselective Synthesis and Evaluation of C6"-Substituted 5a-Carbasugar
      Analogues of SL0101 as Inhibitors of RSK1/2.
AB  - A convergent synthesis of 5a-carbasugar analogues of the n-Pr-variant of SL0101
      is described. The analogues were synthesized in an effort to find compounds with
      potent in vivo efficacy in the inhibition of p90 ribosomal s6 kinase (RSK1/2).
      The synthesis derived the desired C-4 L-rhamnose stereochemistry from quinic acid
      and used a highly selective cuprate addition, NaBH4 reduction, Mitsunobu
      inversion, and alkene dihydroxylation to install the remaining stereochemistry. A
      Pd-catalyzed cyclitolization stereoselectively installed the aglycon at the
      anomeric position. The analogues were evaluated as RSK1/2 inhibitors and found to
      have 3- to 6-fold improved activity.

PMID- 28441026
TI  - Nam7 Hydroxylase Is Responsible for the Formation of the Naphthalenic Ring in the
      Biosynthesis of Neoansamycins.
AB  - Ten new benzenic ansamycins, 5,10-seco-neoansamycins A-J (1-10), were isolated
      from the nam7-disrupted mutant strain SR201nam1OEDeltanam7. These are the
      benzenic counterparts of the neoansamycins, which provide direct evidence that
      the putative hydroxylase Nam7 is involved in the formation of naphthalenic ring
      in neoansamycin biosynthesis and connect benzenic and naphthalenic ansamycins for
      the first time.

PMID- 28441025
TI  - Structures, Interconversions, and Spectroscopy of Iron Carbonyl Clusters with an
      Interstitial Carbide: Localized Metal Center Reduction by Overall Cluster
      Oxidation.
AB  - The syntheses, interconversions, and spectroscopic properties of a set of iron
      carbonyl clusters containing an interstitial carbide are reported. This includes
      the low temperature X-ray structures of the six-iron clusters (Y)2[Fe6(MU6-C)(MU2
      CO)4(CO)12] (1a-c; where Y = NMe4, NEt4, PPh4); the five-iron cluster [Fe5(MU5
      C)(CO)15] (3); and the novel formulation of the five-iron cluster (NMe4)2[Fe5(MU5
      C)(MU2-CO)(CO)13] (4). Also included in this set is the novel charge-neutral
      cluster, [Fe6(MU6-C)(CO)18] (2), for which we were unable to obtain a
      crystallographic structure. As synthetic proof for the identity of 2, we
      performed a closed loop of interconversions within a family of
      crystallographically defined species (1, 3, and 4): [Fe6]2- -> [Fe6]0 -> [Fe5]0 
      > [Fe5]2- -> [Fe6]2-. The structural, spectroscopic, and electronic properties of
      this "missing link" cluster 2 were investigated by IR, Raman, XPS, and Mossbauer
      spectroscopies-as well as by DFT calculations. A single nuCO feature (1965 cm-1)
      in the IR spectrum of 2, as well as a prominent Raman feature (nusymm = 1550 cm
      1), are consistent with the presence of terminal carbonyls and a {(MU6-C)Fe6}
      arrangement of iron centers around the central carbide. The XPS of 2 exhibits a
      higher energy Fe 2p3/2 feature (707.4 eV) as compared to that of 1 (705.5 eV),
      consistent with the two-electron oxidation induced by treatment of 1 with two
      equivalents of [Fc](PF6) under CO atmosphere (for the two added CO ligands). DFT
      calculations indicate two axial and four equatorial Fe sites in 1, all of which
      have the same or similar oxidation states, for example, two Fe(0) and four
      Fe(+0.5). These assignments are supported by Mossbauer spectra for 1, which
      exhibit two closely spaced quadrupole doublets with delta = 0.076 and 0.064 mm s
      1. The high-field Mossbauer spectrum of 2 (4.2 K) exhibits three prominent
      quadrupole doublets with delta = -0.18, -0.11, and +0.41 mm s-1. This indicates
      three pairs of chemically equivalent Fe sites. The first two pairs arise from
      irons of a similar oxidation state, while the last pair arises from irons in a
      different oxidation state, indicating a mixed-valent cluster. Variable field
      Mossbauer spectra for 2 were simulated assuming these two groups and a
      diamagnetic ground state. Taken together, the Mossbauer results and DFT
      calculations for 2 indicate two axial Fe(II) sites and four equatorial sites of
      lower valence, probably Fe(0). In the DFT optimized pentagonal bipyramidal
      structure for 2, the Fe(II)-Ccarbide distances are compressed (~1.84 A), while
      the Fe(0)-Ccarbide distances are elongated (~2.05 A). Analysis of the
      formulations for 1 (closo-square bipyramid) and 2 (nido-pentagonal bipyramid) is
      considered in the context of the textbook electron-counting rules of 14n+2 and
      14n+4 for closo and nido clusters, respectively. This redox-dependent
      intracluster disproportionation of Fe oxidation states is concluded to arise from
      changes in bonding to the central carbide. A similar phenomenon may be promoted
      by the central carbide of the FeMoco cluster of nitrogenase, which may in turn
      stimulate N2 reduction.

PMID- 28441028
TI  - Application of GC/MS Soft Ionization for Isomeric Biological Compound Analysis.
AB  - Isomers are compounds with the same molecular formula. Many different types of
      isomers are ubiquitous and play important roles in living organisms. Despite
      their early discovery, the actual analysis of isomers has been tricky and has
      confounded researchers. Using mass spectrometry (MS) to distinguish or identify
      isomers is an emergent topic and challenge for analytical chemists. We review
      some techniques for analyzing isomers with emphasis on MS, e.g., the roles of ion
      reaction, hydrogen-deuterium exchange, ion mobility mass spectrometry, ion
      spectroscopy, and energy change in producing isomer-specific fragments. In
      particular, soft ionization for gas chromatography-mass spectrometry (GC-MS) is a
      focus in this review. Awareness of the advantages and technical problems of these
      techniques would inspire innovation in future approaches.

PMID- 28441027
TI  - Cardiac Morphometry on Computed Tomography and Exacerbation Reduction with beta
      Blocker Therapy in Chronic Obstructive Pulmonary Disease.

PMID- 28441030
TI  - Measuring Cardiac Output during Cardiopulmonary Exercise Testing.
AB  - Cardiac output is a key parameter in the assessment of cardiac function, and its
      measurement is fundamental to the diagnosis, treatment, and prognostic evaluation
      of all heart diseases. Until recently, cardiac output determination during
      exercise had been only possible through invasive methods, which were not
      practical in the clinical setting. Because [Formula: see text]o2 is cardiac
      output times arteriovenous content difference, evaluation of cardiac output is
      usually included in its measurement. Because of the difficulty of directly
      measuring peak exercise cardiac output, indirect surrogate parameters have been
      proposed, but with only modest clinical usefulness. Direct measurement of cardiac
      output can now be made by several noninvasive techniques, such as rebreathing
      inert gases, impedance cardiology, thoracic bioreactance, estimated continuous
      cardiac output technology, and transthoracic echocardiography coupled to
      cardiopulmonary exercise testing, which allow more definitive results and better
      understanding of the underlying physiopathology.

PMID- 28441031
TI  - Lead accumulation and distribution in maize seedlings: Relevance to biomass
      production and metal phytoextraction.
AB  - Among trace metals, lead is a highly toxic contaminant, being hazardous to humans
      and animals. Application of maize plants for phytoremediation of polluted soils
      and waters has recently been of particular interest. The aim of this work is to
      investigate the Pb-phytoextraction potential of the maize cv. Tzariza used widely
      in Eastern European agriculture. Maize seedlings were exposed in a nutrient
      solution to 1-10000 uM of Pb2+ for 21 days. Lead accumulated mostly in conductive
      tissues and shoots at 0.1 mM and higher concentrations of Pb in growth medium. Pb
      at concentrations of 1 and 10 mM caused an increase in the superoxide anion level
      and the catalase activity in maize leaves. Lead ions were tolerable to maize
      seedlings within a concentration range up to 1000 uM of Pb2+. The levels of lead
      in the nutrient solution above 1 mM resulted in inhibition of the growth of axial
      organs, decrease in leaf area, inhibition of water absorption, and reduction in
      accumulation of biomass. Theoretical considerations indicate that in the
      temperate climates of the phytoremediation with maize may allow annual removal up
      to 90 kg of Pb per km2, depending on the initial level of soil contamination.

PMID- 28441029
TI  - Variable Susceptibility to Cigarette Smoke-Induced Emphysema in 34 Inbred Strains
      of Mice Implicates Abi3bp in Emphysema Susceptibility.
AB  - Chronic obstructive pulmonary disease (COPD) is caused by a complex interaction
      of environmental exposures, most commonly cigarette smoke, and genetic factors.
      Chronic cigarette smoke exposure in the mouse is a commonly used animal model of
      COPD. We aimed to expand our knowledge about the variable susceptibility of
      inbred strains to this model and test for genetic variants associated with this
      trait. To that end, we sought to measure differential susceptibility to cigarette
      smoke-induced emphysema in the mouse, identify genetic loci associated with this
      quantitative trait, and find homologous human genes associated with COPD.
      Alveolar chord length (CL) in 34 inbred strains of mice was measured after 6
      months of exposure to cigarette smoke. After testing for association, we
      connected a murine candidate locus to a published meta-analysis of moderate-to
      severe COPD. We identified deleterious mutations in a candidate gene in silico
      and measured gene expression in extreme strains. A/J was the most susceptible
      strain in our survey (Delta CL 7.0 +/- 2.2 MUm) and CBA/J was the least
      susceptible (Delta CL -0.3 +/- 1.2 MUm). By integrating mouse and human genome
      wide scans, we identified the candidate gene Abi3bp. CBA/J mice harbor predicted
      deleterious variants in Abi3bp, and expression of the gene differs significantly
      between CBA/J and A/J mice. This is the first report of susceptibility to
      cigarette smoke-induced emphysema in 34 inbred strains of mice, and Abi3bp is
      identified as a potential contributor to this phenotype.

PMID- 28441032
TI  - Observation of Intermolecular Hydrogen Bonding Interactions in Biosynthesized and
      Biodegradable Poly [(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] in
      Chloroform and 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP).
AB  - In this work, we describe polymer-solvent interactions in biosynthesized and
      biodegradable poly[(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] (PHBHx) and
      the atactic homopolymer, poly(3-hydroxybutyrate) (a-PHB), which were studied both
      as neat polymers and in solutions of chloroform and 1,1,1,3,3,3-hexafluoro-2
      propanol (HFIP). Specifically, infrared frequency shifts of the carbonyl band
      were observed in semi-crystalline PHBHx, but not in a-PHB, because it cannot form
      the helical conformation required for crystallization. The carbonyl band of PHBHx
      exhibited the high frequency associated with amorphous structure in chloroform
      and the lower frequency traditionally attributed to the helical crystalline
      structure in HFIP. The same results were obtained for a-PHB, demonstrating that
      the helical structure is not required for a lower frequency carbonyl-stretching
      mode. It is proposed that the band shift is due to hydrogen bonding between the
      carbonyl and hydroxyl hydrogen in HFIP. Therefore, the carbonyl frequency
      observed upon crystallization is most likely due to hydrogen bonding between the
      carbonyl and methyl hydrogen of the neighboring polymer chain in the crystal
      lattice as previously suggested.

PMID- 28441033
TI  - Surface-Enhanced Raman Scattering (SERS) Active Gold Nanoparticles Decorated on a
      Porous Polymer Filter.
AB  - In this work, we designed a process to assemble gold nanoparticles onto a three
      dimensional (3D) polymer surface, which can then be monitored using surface
      enhanced Raman scattering (SERS). This work is the first demonstration of the
      assembly of gold nanoparticles on a filter film and in situ measurement with
      Raman spectroscopy. Herein, a polyhexamethylene adipamide (Nylon66) film embedded
      in the organic filter film was used as a template to fabricate a tunable SERS
      active substrate. A "hotspot"-rich gold-nanoparticle-decorated polymer substrate
      for SERS was prepared; this substrate exhibited high sensitivity in trace
      detection of targets. The study was conducted using 4-mercaptobenzoic acid as a
      probe molecule with the aim of comparing the scattering efficiency and the
      homogeneity of the Raman signal on selected substrates. In addition, we used the
      gold-decorated polymer film to detect a biotin-avidin complex. The most powerful
      advantage of the proposed microanalytical device is the in situ SERS application.
      The 3D nanoporous structures described in this work hold strong potential for use
      in various applications such as environmental monitoring and biomolecule
      detection.

PMID- 28441034
TI  - Thrombus Formation at High Shear Rates.
AB  - The final common pathway in myocardial infarction and ischemic stroke is
      occlusion of blood flow from a thrombus forming under high shear rates in
      arteries. A high-shear thrombus forms rapidly and is distinct from the slow
      formation of coagulation that occurs in stagnant blood. Thrombosis at high shear
      rates depends primarily on the long protein von Willebrand factor (vWF) and
      platelets, with hemodynamics playing an important role in each stage of thrombus
      formation, including vWF binding, platelet adhesion, platelet activation, and
      rapid thrombus growth. The prediction of high-shear thrombosis is a major area of
      biofluid mechanics in which point-of-care testing and computational modeling are
      promising future directions for clinically relevant research. Further research in
      this area will enable identification of patients at high risk for arterial
      thrombosis, improve prevention and treatment based on shear-dependent biological
      mechanisms, and improve blood-contacting device design to reduce thrombosis risk.

PMID- 28441035
TI  - Arsenic and fluoride removal by potato peel and rice husk (PPRH) ash in aqueous
      environments.
AB  - Finding appropriate adsorbent may improve the quality of drinking water in those
      regions where arsenic (As) and fluoride (F-) are present in geological
      formations. In this study, we evaluated the efficiency of potato peel and rice
      husk ash (PPRH-ash)-derived adsorbent for the removal of As and F from
      contaminated water. Evaluation was done in batch adsorption experiments, and the
      effect of pH, initial adsorbate concentration, contact time, and adsorbent dose
      were studied. Characteristics of adsorbents were analyzed using scanning electron
      micropcope (SEM) and Fourier transform infrared (FTIR) spectroscopy. Both the
      Langmuir and Freundlich isotherm models fitted well for F- and As sorption
      process. The maximum adsorption capacity of adsorbent for As and F- was 2.17 MUg
      g-1 and 2.91 mg g-1, respectively. The As and Fi removal was observed between pH
      7 and 9. The sorption process was well explained with pseudo-second order kinetic
      model. Arsenic adsorption was not decreased in the presence of carbonate and
      sulfate. Results from this study demonstrated potential utility of this
      agricultural biowaste, which could be developed into a viable filtration
      technology for As and F- removal in As- and F-contaminated water streams.

PMID- 28441036
TI  - Application of Arthrospira (Spirulina) platensis biomass for silver removal from
      aqueous solutions.
AB  - The cyanobacterium Arthrospira (Spirulina) platensis was used to study the
      process of silver biosorption. Effects of various parameters such as contact
      time, dosage of biosorbent, initial pH, temperature, and initial concentration of
      Ag(I) were investigated for a batch adsorption system. The optimal biosorption
      conditions were determined as pH 5.0, biosorbent dosage of 0.4 g, and initial
      silver concentration of 30 mg/L. Equilibrium adsorption data were analyzed by the
      Langmuir and Freundlich models - however, the Freundlich model provided a better
      fit to the experimental data. The kinetic data fit the pseudo-second-order model
      well, with a correlation coefficient of 0.99. The analysis of thermodynamic
      parameters (DeltaG degrees , DeltaH degrees  and DeltaS degrees ) revealed that
      the adsorption process of silver ion by spirulina biomass was exothermic and
      spontaneous (DeltaG degrees  < 0), and exothermic (DeltaH degrees  < 0) process.
      The biosorption capacity of biomass A. platensis serves as a basis for the
      development of green technology for environmental remediation.

PMID- 28441037
TI  - Preseason Anxiety and Depressive Symptoms and Prospective Injury Risk in
      Collegiate Athletes.
AB  - BACKGROUND: Psychological risk factors are increasingly recognized as important
      in sport-related injury prevention. Understanding how these psychological factors
      may affect the risk of injuries could help design effective prevention programs.
      PURPOSE: To determine the effect of reported preseason anxiety and depressive
      symptoms on the risk of injuries during a prospective season in a cohort of
      collegiate athletes. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS:
      Collegiate athletes participating in 4 men's sports and 5 women's sports from 2
      National Collegiate Athletic Association (NCAA) Division I universities were
      enrolled and prospectively followed during the 2007-2011 seasons. Preseason
      anxiety and depressive symptoms were measured at enrollment. Injuries occurring
      during the season were reported by certified athletic trainers. The injury
      incidence rate was calculated as the total number of injuries divided by the
      total number of athlete-exposures (ie, games and practices). RESULTS: Of 958
      enrolled athletes (response rate of 90.3%), 389 (40.6%) athletes sustained a
      total of 597 injuries. At preseason, 276 (28.8%) athletes reported anxiety
      symptoms, and 208 (21.7%) reported depressive symptoms. Among athletes reporting
      any of these symptoms, 48.5% (n = 158) reported having both anxiety and
      depressive symptoms. Athletes with preseason anxiety symptoms had a significantly
      higher injury incidence rate compared with athletes without anxiety symptoms
      (rate ratio [RR], 2.3; 95% CI, 2.0-2.6), adjusting for age, race, body mass
      index, history of injuries 12 months before baseline, and university attended,
      and this was observed for both male and female athletes. Only male athletes who
      reported co-occurring preseason depressive and anxiety symptoms had a
      significantly increased injury risk (RR, 2.1; 95% CI, 1.6-2.6) compared with male
      athletes who reported no co-occurring symptoms. However, no such increase in the
      injury risk was observed among female athletes or male athletes who reported
      preseason depressive symptoms but no anxiety symptoms. CONCLUSION: Athletes with
      anxiety symptoms at preseason were at an increased risk of injuries during the
      prospective season. Targeted programs could focus on psychological health and
      injury prevention for athletes, especially for those exhibiting symptoms at
      preseason.

PMID- 28441038
TI  - Phytoextraction of nitrogen and phosphorus by crops grown in a heavily manured
      Dark Brown Chernozem under contrasting soil moisture conditions.
AB  - Phytoextraction of excess nutrients by crops in soils with a long history of
      manure application may be a viable option for reducing the nutrient levels. This
      greenhouse study examined the effectiveness of six growth cycles (40 d each) of
      barley, canola, corn, oat, pea, soybean, and triticale at extracting nitrogen (N)
      and phosphorus (P) from a Dark Brown Chernozem that had received 180 Mg ha-1 (wet
      wt.) of beef cattle feedlot manure annually for 38 years. Moisture content during
      the study was maintained at either 100% or 50% soil field capacity (SFC).
      Repeated cropping resulted in an overall decrease in dry matter yield (DMY). The
      decrease in N and P uptake relative to Cycle 1 was fastest for the cereal grains
      and less pronounced for the two legumes. However, cumulative N uptake values were
      significantly greater for corn than the other crops under both moisture regimes.
      The reduction in soil N was greater under the 100% than the 50% SFC. These
      results indicate that repeated cropping can be a useful management practice for
      reducing N and P levels in a heavily manured soil. The extent of reduction will
      be greater for crops with high biomass production under adequate moisture supply.

PMID- 28441039
TI  - High-Throughput Processing to Preserve Viable Cells: A Precision Medicine
      Initiative Cohort Program Workshop.
AB  - Conventionally, biobanks supporting clinical research studies have preserved
      serum, plasma, urine, saliva, a variety of tissue types, and stool. With the
      emergence of increasingly sophisticated technologies for analyzing single cells,
      there is growing interest in preserving viable blood cells for future functional
      studies. The new All of Us Research Program (formerly the Precision Medicine
      Initiative Cohort Program) biobank plans to house samples from a million or more
      individuals as part of a cohort with rich phenotypic data and longitudinal follow
      up ( www.nih.gov/research-training/allofus-research-program ). Storage of viable
      cells for future single-cell analysis offers the promise of new biology,
      discovery of novel biomarkers, and advances toward the goal of precision
      medicine. A workshop was held in the summer of 2016 to evaluate the case for
      preservation of viable mononuclear blood cells and its feasibility within the
      collection plan for the biobank.

PMID- 28441041
TI  - The Child Network for Parents to Track Their Child's Mood and Behavior.
AB  - INTRODUCTION: A wide range of psychiatric disorders are common in young children,
      especially in those at high risk because of a parent with a unipolar or bipolar
      mood disorder in the United States. Yet in part because most children are seen in
      primary care, these illnesses are often not recognized or treated in a timely
      fashion. To begin to address this problem, we started the Child Network. METHODS:
      The Child Network is for parents of children age 2-12 with mood or behavioral
      symptoms or at high risk for them. The parents rate the severity of symptoms of
      depression, anxiety, attention-deficit/hyperactivity disorder (ADHD),
      oppositional behavior, and mania on a once a week basis on a secure website under
      a Johns Hopkins Intramural Review Board (IRB)-approved protocol. These ratings
      can then be printed out along with any treatments given to aide in visualization
      of symptom course. A demographics form, which includes diagnoses given to the
      child in the community, and a symptom checklist are filled out upon Network
      entry. We report on the retrospective diagnoses and prospective treatment of the
      first 65 parents to join the Network. RESULTS: The most common diagnoses were
      anxiety disorders and ADHD followed by disruptive behavioral disorders and
      bipolar spectrum disorders. Prospective ratings of two or more consecutive weeks
      of moderate to severe rating in any of the five symptom domains paralleled these
      diagnoses given in the community. Atypical antipsychotics, anticonvulsant mood
      stabilizers, and medications for ADHD were among the most widely used drugs. An
      illustrated example of symptom course is presented. DISCUSSION: Many children
      continued to show substantial symptom severity despite treatment with an average
      of 2.2 medications. The Child Network provides a useful longitudinal approach to
      visualize the course of symptoms, which should help lead to earlier and more
      effective treatment.

PMID- 28441042
TI  - Aberrantly expressed long noncoding RNAs in recurrent implantation failure: A
      microarray related study.
AB  - : Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs longer than 200
      nucleotides. They were long regarded as transcription noise for their low
      expression and non-protein coding features. Recent published reports indicate
      that lncRNAs are involved in virtually every aspect of human biology. We aimed to
      profile the endometrial lncRNA expression pattern in women with recurrent
      implantation failure (RIF) and predict the function of the genes of the
      dysregulated lncRNA transcripts. Endometrial samples (24) were collected during
      window of implantation (14 RIF women and 10 women who conceived after embryo
      transfer). For the microarray study, 7 RIF endometrium and 5 control endometrium
      were selected, and quantitative real-time PCR (RT-qPCR) was performed on the rest
      of the endometrial samples to validate the microarray results. After that, lncRNA
      mRNA co-expression analysis, GO analysis, KEGG analysis, and lncRNA-transcript
      factor (TF) analysis were carried out to analyze the gene functions of the
      dysregulated lncRNA transcripts. We detected a total of 197 lncRNA transcripts
      that were dysregulated in RIF endometrium compared with the control group. The
      relative expression levels of eight selected lncRNA transcripts were validated by
      RT-qPCR and were in accordance with the microarray outcomes. GO and KEGG analyses
      revealed that the coexpressed mRNA transcripts were involved in pathways that may
      affect endometrial receptivity such as cell adhesion. The lncRNA target
      predictions provided potential TF targets of the dysregulated lncRNA transcripts.
      Our results indicate that lncRNA expression profiles of RIF endometrium were
      different from that of normal receptive endometrial, suggesting that lncRNAs may
      regulate endometrial receptivity. ABBREVIATIONS: GO: Gene Oncology; GFs: growth
      factors; KEGG: Kyoto Encyclopedia of Genes and Genomes; lncRNAs: long noncoding
      RNAs; PCA3: prostate cancer antigen 3; RT-qPCR: quantitative real-time PCR; RIF:
      recurrent implantation failure; STK: serine/threonine kinase; TF: transcription
      factor; WOI: window of implantation.

PMID- 28441043
TI  - Hydropneumothorax from a Ruptured Coccidioides Cavity.

PMID- 28441044
TI  - Pharmacokinetics and pharmacodynamics of midazolam following intravenous and
      intramuscular administration to sheep.
AB  - OBJECTIVE To determine the pharmacokinetic and pharmacodynamic effects of
      midazolam following IV and IM administration in sheep. ANIMALS 8 healthy adult
      rams. PROCEDURES Sheep were administered midazolam (0.5 mg/kg) by the IV route
      and then by the IM route 7 days later in a crossover study. Physiologic and
      behavioral variables were assessed and blood samples collected for determination
      of plasma midazolam and 1-hydroxymidazolam (primary midazolam metabolite)
      concentrations immediately before (baseline) and at predetermined times for 1,440
      minutes after midazolam administration. Pharmacokinetic parameters were
      calculated by compartmental and noncompartmental methods. RESULTS Following IV
      administration, midazolam was rapidly and extensively distributed and rapidly
      eliminated; mean +/- SD apparent volume of distribution, elimination half-life,
      clearance, and area under the concentration-time curve were 838 +/- 330 mL/kg,
      0.79 +/- 0.44 hours, 1,272 +/- 310 mL/h/kg, and 423 +/- 143 h.ng/mL,
      respectively. Following IM administration, midazolam was rapidly absorbed and
      bioavailability was high; mean +/- SD maximum plasma concentration, time to
      maximum plasma concentration, area under the concentration-time curve, and
      bioavailability were 820 +/- 268 ng/mL, 0.46 +/- 0.26 hours, 1,396 +/- 463
      h.ng/mL, and 352 +/- 148%, respectively. Respiratory rate was transiently
      decreased from baseline for 15 minutes after IV administration. Times to peak
      sedation and ataxia after IV administration were less than those after IM
      administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated midazolam
      was a suitable short-duration sedative for sheep, and IM administration may be a
      viable alternative when IV administration is not possible.

PMID- 28441046
TI  - Characterization of long-term elution of platinum from carboplatin-impregnated
      calcium sulfate hemihydrate beads in vitro by two distinct sample collection
      methods.
AB  - OBJECTIVE To characterize long-term elution of platinum from carboplatin
      impregnated calcium sulfate hemihydrate (CI-CSH) beads in vitro by comparing 2
      distinct sample collection methods designed to mimic 2 in vivo environments.
      SAMPLES 162 CI-CSH beads containing 4.6 mg of carboplatin (2.4 mg of
      platinum/bead). PROCEDURES For method 1, which mimicked an in vivo environment
      with rapid and complete fluid exchange, each of 3 plastic 10-mL conical tubes
      contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained
      by evacuation of all fluid at 1, 2, 3, 6, 9, and 12 hours and 1, 2, 3, 6, 9, 12,
      15, 18, 22, 26, and 30 days. Five milliliters of fresh PBS solution was then
      added to each tube. For method 2, which mimicked an in vivo environment with no
      fluid exchange, each of 51 tubes (ie, 3 tubes/17 sample collection times)
      contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained
      from the assigned tubes for each time point. All samples were analyzed for
      platinum content by inductively coupled plasma-mass spectrometry. RESULTS
      Platinum was released from CI-CSH beads for 22 to 30 days. Significant
      differences were found in platinum concentration and percentage of platinum
      eluted from CI-CSH beads over time for each method. Platinum concentrations and
      elution percentages in method 2 samples were significantly higher than those of
      method 1 samples, except for the first hour measurements. CONCLUSIONS AND
      CLINICAL RELEVANCE Sample collection methods 1 and 2 may provide estimates of the
      minimum and maximum platinum release, respectively, from CI-CSH beads in vivo.

PMID- 28441045
TI  - Effects of topical application of silver sulfadiazine cream, triple antimicrobial
      ointment, or hyperosmolar nanoemulsion on wound healing, bacterial load, and
      exuberant granulation tissue formation in bandaged full-thickness equine skin
      wounds.
AB  - OBJECTIVE To determine the effects of 3 topically applied treatments (1% silver
      sulfadiazine cream [SSC], triple antimicrobial ointment [TAO], and hyperosmolar
      nanoemulsion [HNE]) on microbial counts, exuberant granulation tissue (EGT)
      development, and reepithelialization of contaminated wounds at the distal aspect
      of the limbs of horses. ANIMALS 8 healthy adult horses. PROCEDURES A 2.5 * 2.5
      cm, full-thickness, cutaneous wound was created at the dorsal aspect of each
      metacarpus and metatarsus (1 wound/limb/horse), covered with nonadhesive
      dressing, and bandaged. Wounds were inoculated with bacteria and fungi the next
      day. Each wound on a given horse was randomly assigned to 1 of 4 treatment groups
      (SSC, TAO, HNE, or no topical treatment [control]). Bandage changes, culture of
      wound samples, treatments, photography for wound measurements, and biopsy were
      performed at predetermined time points. Time (days) until wound closure, number
      of EGT excisions, microbial counts, and scores for selected histologic
      characteristics were compared among groups. RESULTS Median time to wound closure
      for all groups was 42 days. Time to wound closure and histologic characteristics
      of wound healing did not differ among groups. Least squares mean microbial counts
      were significantly higher for HNE-treated wounds on days 9 and 21, compared with
      SSC-treated and TAO-treated wounds, but not controls. Proportions of SSC-treated
      (7/8) or HNE-treated (5/8) wounds needing EGT excision were significantly greater
      than that of TAO-treated (1/8) wounds. The proportion of SSC-treated wounds with
      EGT excision was greater than that of controls (3/8). CONCLUSIONS AND CLINICAL
      RELEVANCE None of the treatments resulted in more rapid wound closure, compared
      with that for untreated control wounds under the study conditions. When treatment
      is warranted, TAO may help to limit EGT formation.

PMID- 28441047
TI  - Distribution of T-cell markers CD4 and CD8alpha in lymphoid organs of healthy
      newborn, juvenile, and adult highland-plateau yaks.
AB  - OBJECTIVE: To investigate the distribution of T-cell markers (CD4 and CD8alpha)
      in lymphoid organs of newborn, juvenile, and adult yaks. ANIMALS: 15 healthy male
      yaks of various ages from highland plateaus. PROCEDURES: Yaks were allocated to
      groups on the basis of age (newborn [1 to 7 days old; n = 5], juvenile [5 to 7
      months old; 5], and adult [3 to 4 years old; 5]). The thymus, spleen, 5
      mesenteric lymph nodes, and 5 hemal nodes were harvested from each yak within 10
      minutes after euthanasia. Morphological characteristics of those lymphoid organs
      were assessed by histologic examination; expression of CD4 and CD8alpha mRNAs and
      proteins were measured by quantitative real-time PCR assay and
      immunohistochemical staining. RESULTS: Among the lymphoid organs evaluated,
      expressions of CD4 and CD8alpha mRNAs were highest in the thymus in all age
      groups. In newborn lymphoid organs, CD4 mRNA expression and CD4+ cell
      distribution were more predominant, whereas in juvenile and adult lymphoid
      organs, CD8alpha mRNA expression and CD8alpha+ cell distribution were more
      predominant. The CD4+ and CD8alpha+ cells were mainly located in the cortex and
      medulla of the thymus, the medulla of the hemal nodes and mesenteric lymph nodes,
      the periarteriolar lymphoid sheaths, and the red pulp of the spleen. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results indicated that the CD4 mRNA expression and CD4+ T
      cell distribution in yak lymphoid organs decreased and CD8alpha mRNA expression
      and CD8alpha+ T-cell distribution increased with age. Moreover, CD8alpha+ cells
      were present in the follicles of yaks' secondary lymphoid organs, which differs
      from findings for other mammals.

PMID- 28441048
TI  - Influence of body weight and body conformation on the pressure-volume curve
      during capnoperitoneum in dogs.
AB  - OBJECTIVE To evaluate the pressure-volume relationship during capnoperitoneum in
      dogs and effects of body weight and body conformation. ANIMALS 86 dogs scheduled
      for routine laparoscopy. PROCEDURES Dogs were allocated into 3 groups on the
      basis of body weight. Body measurements, body condition score, and body
      conformation indices were calculated. Carbon dioxide was insufflated into the
      abdomen with a syringe, and pressure was measured at the laparoscopic cannula.
      Volume and pressure data were processed, and the yield point, defined by use of a
      cutoff volume (COV) and cutoff pressure (COP), was calculated. RESULTS 20 dogs
      were excluded because of recording errors, air leakage attributable to surgical
      flaws, or trocar defects. For the remaining 66 dogs, the pressure-volume curve
      was linear-like until the yield point was reached, and then it became visibly
      exponential. Mean +/- SD COP was 5.99 +/- 0.805 mm Hg. No correlation was
      detected between yield point, body variables, or body weight. Mean COV was
      1,196.2 +/- 697.9 mL (65.15 +/- 20.83 mL of CO2/kg), and COV was correlated
      significantly with body weight and one of the body condition indices but not with
      other variables. CONCLUSION AND CLINICAL RELEVANCE In this study, there was a
      similar COP for all dogs of all sizes. In addition, results suggested that
      increasing the abdominal pressure after the yield point was reached did not
      contribute to a substantial increase in working space in the abdomen. No
      correlation was found between yield point, body variables, and body weight.

PMID- 28441050
TI  - Comparison of platelet function and viscoelastic test results between healthy
      dogs and dogs with naturally occurring chronic kidney disease.
AB  - OBJECTIVE To compare platelet function and viscoelastic test results between
      healthy dogs and dogs with chronic kidney disease (CKD) to assess whether dogs
      with CKD have platelet dysfunction and altered blood coagulation. ANIMALS 10
      healthy control dogs and 11 dogs with naturally occurring CKD. PROCEDURES Blood
      and urine were collected once from each dog for a CBC, serum biochemical
      analysis, urinalysis, and determination of the urine protein-to-creatinine ratio,
      prothrombin time, activated partial thromboplastin time, plasma fibrinogen
      concentration, and antithrombin activity. Closure time was determined by use of a
      platelet function analyzer and a collagen-ADP platelet agonist.
      Thromboelastography (TEG) variables (reaction time, clotting time, alpha angle,
      maximum amplitude, and global clot strength [G value]) were determined by use of
      recalcified nonactivated TEG. Platelet expression of glycoprotein Ib (GPIb;
      receptor for von Willebrand factor), integrin alphaIIbbeta3 (alphaIIbbeta3;
      receptor for fibrinogen), and P-selectin (marker for platelet activation) was
      assessed by flow cytometry. RESULTS Compared with healthy control dogs, the
      median closure time was prolonged, the median maximum amplitude and G value were
      increased, and the median clotting time was decreased for dogs with CKD. Platelet
      expression of both alphaIIbbeta3 and P-selectin was also significantly increased
      for dogs with CKD, compared with that for control dogs. Platelet expression of
      GPIb, alphaIIbbeta3, and P-selectin was not correlated with closure time or any
      TEG variable. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs with
      CKD frequently had evidence of platelet dysfunction and hypercoagulability that
      were not totally attributable to alterations in platelet surface expression of
      GPIb, alphaIIbbeta3, and P-selectin.

PMID- 28441051
TI  - Diffusion-weighted magnetic resonance imaging of the brain of neurologically
      normal dogs.
AB  - : OBJECTIVE To acquire MRI diffusion data (apparent diffusion coefficient [ADC]
      and fractional anisotropy [FA] values, including separate measures for gray and
      white matter) at 3.0 T for multiple locations of the brain of neurologically
      normal dogs. ANIMALS: 13 neurologically normal dogs recruited from a group of
      patients undergoing tibial plateau leveling osteotomy. PROCEDURES: MRI duration
      ranged from 20 to 30 minutes, including obtaining preliminary images to exclude
      pathological changes (T2-weighted fluid-attenuated inversion recovery transverse
      and dorsal images) and diffusion-weighted images. , RESULTS: Globally, there were
      significant differences between mean values for gray and white matter in the
      cerebral lobes and cerebellum for ADC (range of means for gray matter, 0.8349 *
      10-3 s/mm2 to 0.9273 * 10-3 s/mm2; range of means for white matter, 0.6897 * 10-3
      s/mm2 to 0.7332 * 10-3 s/mm2) and FA (range of means for gray matter, 0.1978 to
      0.2364; range of means for white matter, 0.5136 to 0.6144). These values also
      differed among cerebral lobes. In most areas, a positive correlation was detected
      between ADC values and patient age but not between FA values and patient age.
      CONCLUSIONS AND CLINICAL RELEVANCE: Cerebral interlobar and cerebellar diffusion
      values differed significantly, especially in the gray matter. Information about
      diffusion values in neurologically normal dogs may be used to diagnose and
      monitor abnormalities and was the first step in determining the clinical use of
      diffusion imaging. This information provided an important starting point for the
      clinical application of diffusion imaging of the canine brain.

PMID- 28441052
TI  - Effects of hyaluronan alone or in combination with chondroitin sulfate and N
      acetyl-d-glucosamine on lipopolysaccharide challenge-exposed equine fibroblast
      like synovial cells.
AB  - OBJECTIVE To investigate effects of hyaluronic acid (HA) or HA combined with
      chondroitin sulfate (CS) and N-acetyl-d-glucosamine (NAG) by use of a
      lipopolysaccharide (LPS) in vitro method. SAMPLE Monolayer cultures of synovial
      cells from 4 adult horses. PROCEDURES Synovial cell cultures were untreated or
      treated with HA alone or HA-CS-NAG for 24 hours, subsequently unchallenged or
      challenge-exposed with 2 LPS concentrations (20 and 50 ng/mL) for 2 hours, and
      retreated with HA or HA-CS-NAG for another 24 hours. Cellular morphology of
      cultures was evaluated at 0, 24 (before LPS), 26 (after LPS), and 50 (24 hours
      after end of LPS) hours. At 50 hours, cell number and viability and prostaglandin
      (PG) E2, interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and cyclooxygenase
      (COX)-2 production were measured. RESULTS LPS challenge exposure induced a
      significant loss of characteristic synovial cell morphology, decrease in cell
      viability, and increases in concentrations of PGE2, IL-6, MMP-3, and COX-2. Cells
      treated with HA or HA-CS-NAG had significantly better viability and morphology
      scores and lower concentrations of PGE2, MMP-3, IL-6, and COX-2 than untreated
      LPS challenge-exposed cells. Cells treated with HA had significantly better
      morphology scores at 50 hours than cells treated with HA-CS-NAG. Cells treated
      with HA-CS-NAG had significantly superior suppression of LPS-induced production
      of PGE2, IL-6, and MMP-3 than cells treated with HA alone. CONCLUSIONS AND
      CLINICAL RELEVANCE HA and HA-CS-NAG protected synovial cells from the effects of
      LPS. Treatment with HA-CS-NAG had the greatest anti-inflammatory effect. These
      results supported the protective potential of HA and HA-CS-NAG treatments.

PMID- 28441053
TI  - Evaluation of oxygen administration with a high-flow nasal cannula to clinically
      normal dogs.
AB  - OBJECTIVE To evaluate the safety and efficacy of oxygen administration by use of
      a high-flow nasal cannula (HFNC) in sedated clinically normal dogs. ANIMALS 6
      healthy adult dogs undergoing routine dental prophylaxis. PROCEDURES Dogs were
      sedated with butorphanol tartrate and dexmedetomidine. An esophageal balloon
      catheter was inserted into the esophagus, a double-pronged nasal cannula was
      inserted into the nares, and a catheter was inserted into the dorsal pedal
      artery. Dogs were positioned in right lateral recumbency. After a 6-minute
      acclimation period, baseline blood gas values and transpulmonary pressure were
      measured. Dogs then received supplemental oxygen via conventional oxygen therapy
      (COT) at a rate of 100 mL/kg/min (COT-100 treatment) and an HFNC at a rate of 20
      L/min (HF-20 treatment) and 30 L/min (HF-30 treatment). Arterial blood gas and
      transpulmonary pressure were measured after a 6-minute acclimation period for
      each oxygen delivery method. Radiographs were obtained before and after oxygen
      administration to evaluate gastric distension. RESULTS Median Pao2 was
      significantly higher for HF-20 (519.9 mm Hg) and HF-30 (538.1 mm Hg) treatments,
      compared with median Pao2 for the COT-100 treatment (202.9 mm Hg). The Pao2 did
      not differ significantly between the HF-20 and HF-30 treatments. There was no
      significant difference in Paco2 or change in transpulmonary pressure between
      baseline and any oxygen delivery method. CONCLUSIONS AND CLINICAL RELEVANCE In
      this study, HFNC appeared to be a safe and effective method for oxygen delivery
      to sedated healthy dogs. Further studies are needed to evaluate use of HFNCs for
      oxygen administration to hypoxemic patients.

PMID- 28441054
TI  - Biomechanical and histologic evaluation of the effects of underwater treadmill
      exercise on horses with experimentally induced osteoarthritis of the middle
      carpal joint.
AB  - OBJECTIVE To evaluate the effects of exercise in an underwater treadmill (UWT) on
      forelimb biomechanics and articular histologic outcomes in horses with
      experimentally induced osteoarthritis of the middle carpal joint. ANIMALS 16
      horses. PROCEDURES An osteochondral fragment was induced arthroscopically (day 0)
      in 1 middle carpal joint of each horse. Beginning on day 15, horses were assigned
      to exercise in a UWT or in the UWT without water (simulating controlled hand
      walking) at the same speed, frequency, and duration. Thoracic and pelvic limb
      ground reaction forces, thoracic limb kinematics, and electromyographic results
      for select thoracic limb muscles acting on the carpi were collected on days -7
      (baseline), 14, 42, and 70. Weekly evaluations included clinical assessments of
      lameness, response to carpal joint flexion, and goniometric measurements of
      thoracic limb articulations. At study conclusion, articular cartilage and
      synovial membrane from the middle carpal joints was histologically examined.
      RESULTS Exercise in a UWT significantly reduced synovial membrane inflammation
      and resulted in significant clinical improvements with regard to symmetric
      thoracic limb loading, uniform activation patterns of select thoracic limb
      muscles, and return to baseline values for carpal joint flexion, compared with
      results for horses with simulated hand walking. CONCLUSIONS AND CLINICAL
      RELEVANCE Overall improvements in thoracic limb function, joint range of motion,
      and synovial membrane integrity indicated that exercise in a UWT was a
      potentially viable therapeutic option for the management of carpal joint
      osteoarthritis in horses.

PMID- 28441055
TI  - Ex vivo biomechanical evaluation of pigeon (Columba livia) cadaver intact humeri
      and ostectomized humeri stabilized with caudally applied titanium locking plate
      or stainless steel nonlocking plate constructs.
AB  - OBJECTIVE To evaluate mechanical properties of pigeon (Columba livia) cadaver
      intact humeri versus ostectomized humeri stabilized with a locking or nonlocking
      plate. SAMPLE 30 humeri from pigeon cadavers. PROCEDURES Specimens were allocated
      into 3 groups and tested in bending and torsion. Results for intact pigeon humeri
      were compared with results for ostectomized humeri repaired with a titanium 1.6
      mm screw locking plate or a stainless steel 1.5-mm dynamic compression plate; the
      ostectomized humeri mimicked a fracture in a thin cortical bone. Locking plates
      were secured with locking screws (2 bicortical and 4 monocortical), and
      nonlocking plates were secured with bicortical nonlocking screws. Constructs were
      cyclically tested nondestructively in 4-point bending and then tested to failure
      in bending. A second set of constructs were cyclically tested non-destructively
      and then to failure in torsion. Stiffness, strength, and strain energy of each
      construct were compared. RESULTS Intact specimens were stiffer and stronger than
      the repair groups for all testing methods, except for nonlocking constructs,
      which were significantly stiffer than intact specimens under cyclic bending.
      Intact bones had significantly higher strain energies than locking plates in both
      bending and torsion. Locking and nonlocking plates were of equal strength and
      strain energy, but not stiffness, in bending and were of equal strength,
      stiffness, and strain energy in torsion. CONCLUSIONS AND CLINICAL RELEVANCE
      Results for this study suggested that increased torsional strength may be needed
      before bone plate repair can be considered as the sole fixation method for avian
      species.

PMID- 28441056
TI  - Evaluation of gastric emptying time, gastrointestinal transit time, sedation
      score, and nausea score associated with intravenous constant rate infusion of
      lidocaine hydrochloride in clinically normal dogs.
AB  - OBJECTIVE To quantify nausea and sedation scores, gastric emptying time, and
      gastrointestinal transit time after IV administration of a lidocaine
      hydrochloride bolus followed by a constant rate infusion (CRI) in clinically
      normal dogs. ANIMALS 6 Beagles. PROCEDURES In a crossover study, dogs were fed
      thirty 1.5-mm barium-impregnated spheres (BIPS) and received a saline (0.9% NaCl)
      solution bolus (0.05 mL/kg) IV (time 0) followed by a CRI at 10 mL/h, a lidocaine
      bolus (1 mg/kg) IV followed by a CRI at 25 MUg/kg/min, or a lidocaine bolus (1
      mg/kg) IV followed by a CRI at 50 MUg/kg/min; CRIs were for 12 hours. Nausea and
      sedation scores were assessed and abdominal radiographs obtained immediately
      after feeding of BIPS and every hour for 12 hours and again 16 hours after CRI
      start. Percentage of BIPSs in the small and large intestines, gastric emptying
      time, and gastrointestinal transit time were assessed. RESULTS Gastric emptying
      time did not differ significantly among treatments. Significantly more BIPS were
      in the large intestine 4 to 7 hours after treatment start for the 50-MUg/kg/min
      treatment than for the other 2 treatments. Six hours after treatment start,
      significantly more BIPS were in the large intestine for the 25-MUg/kg/min
      treatment than for the saline solution treatment. Higher sedation and nausea
      scores were associated with the 50-MUg/kg/min CRI. CONCLUSIONS AND CLINICAL
      RELEVANCE In clinically normal dogs, lidocaine CRI did not significantly affect
      gastric emptying. However, gastrointestinal transit time was mildly decreased and
      sedation and nausea scores increased in dogs administered a lidocaine CRI at
      clinically used doses.

PMID- 28441057
TI  - Oxidative Stress.
AB  - Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage
      to biomolecules, maintenance of a physiological level of oxidant challenge,
      termed oxidative eustress, is essential for governing life processes through
      redox signaling. Recent interest has focused on the intricate ways by which redox
      signaling integrates these converse properties. Redox balance is maintained by
      prevention, interception, and repair, and concomitantly the regulatory potential
      of molecular thiol-driven master switches such as Nrf2/Keap1 or NF-kappaB/IkappaB
      is used for system-wide oxidative stress response. Nonradical species such as
      hydrogen peroxide (H2O2) or singlet molecular oxygen, rather than free-radical
      species, perform major second messenger functions. Chemokine-controlled NADPH
      oxidases and metabolically controlled mitochondrial sources of H2O2 as well as
      glutathione- and thioredoxin-related pathways, with powerful enzymatic back-up
      systems, are responsible for fine-tuning physiological redox signaling. This
      makes for a rich research field spanning from biochemistry and cell biology into
      nutritional sciences, environmental medicine, and molecular knowledge-based redox
      medicine.

PMID- 28441058
TI  - Protein Misfolding Diseases.
AB  - The majority of protein molecules must fold into defined three-dimensional
      structures to acquire functional activity. However, protein chains can adopt a
      multitude of conformational states, and their biologically active conformation is
      often only marginally stable. Metastable proteins tend to populate misfolded
      species that are prone to forming toxic aggregates, including soluble oligomers
      and fibrillar amyloid deposits, which are linked with neurodegeneration in
      Alzheimer and Parkinson disease, and many other pathologies. To prevent or
      regulate protein aggregation, all cells contain an extensive protein homeostasis
      (or proteostasis) network comprising molecular chaperones and other factors.
      These defense systems tend to decline during aging, facilitating the
      manifestation of aggregate deposition diseases. This volume of the Annual Review
      of Biochemistry contains a set of three articles addressing our current
      understanding of the structures of pathological protein aggregates and their
      associated disease mechanisms. These articles also discuss recent insights into
      the strategies cells have evolved to neutralize toxic aggregates by sequestering
      them in specific cellular locations.

PMID- 28441059
TI  - Effectiveness of Neuromuscular Training Based on the Neuromuscular Risk Profile.
AB  - BACKGROUND: The effects of targeted neuromuscular training (TNMT) on movement
      biomechanics associated with the risk of anterior cruciate ligament (ACL)
      injuries are currently unknown. Purpose/Hypotheses: To determine the
      effectiveness of TNMT specifically designed to increase trunk control and hip
      strength. The hypotheses were that (1) TNMT would decrease biomechanical and
      neuromuscular factors related to an increased ACL injury risk and (2) TNMT would
      decrease these biomechanical and neuromuscular factors to a greater extent in
      athletes identified as being at a high risk for future ACL injuries. STUDY
      DESIGN: Controlled laboratory study. METHODS: Female athletes who participated in
      jumping, cutting, and pivoting sports underwent 3-dimensional biomechanical
      testing before the season and after completing TNMT. During testing, athletes
      performed 3 different types of tasks: (1) drop vertical jump, (2) single-leg
      drop, and (3) single-leg cross drop. Analysis of covariance was used to examine
      the treatment effects of TNMT designed to enhance core and hip strength on
      biomechanical and neuromuscular characteristics. Differences were also evaluated
      by risk profile. Differences were considered statistically significant at P <
      .05. RESULTS: TNMT significantly increased hip external rotation moments and
      moment impulses, increased peak trunk flexion, and decreased peak trunk
      extension. Athletes with a high risk before the intervention (risk profile III)
      had a more significant treatment effect of TNMT than low-risk groups (risk
      profiles I and II). CONCLUSION: TNMT significantly improved proximal
      biomechanics, including increased hip external rotation moments and moment
      impulses, increased peak trunk flexion, and decreased peak trunk extension. TNMT
      that focuses exclusively on proximal leg and trunk risk factors is not, however,
      adequate to induce significant changes in frontal-plane knee loading.
      Biomechanical changes varied across the risk profile groups, with higher risk
      groups exhibiting greater improvements in their biomechanics.

PMID- 28441060
TI  - Characterization of a Standardized Ex-vivo Porcine Model to Assess Short Term
      Intraocular Pressure Changes and Trabecular Meshwork Vitality After Pars Plana
      Vitrectomy with Different Silicone Oil and BSS Tamponades.
AB  - PURPOSE: The aim of this study was to characterize a standardized porcine ex-vivo
      testing system for intraocular pressure (IOP) monitoring after vitrectomy with
      different endotamponades. METHODS: Twenty-four pig eyes, six per endotamponade
      group were obtained immediately postmortem. After pars plana vitrectomy, vitreous
      substitutes (silicone oil 1000 mPas, 2000 mPas, 5000 mPas, and Balanced Salt
      Solution (BSS)) were instillated and IOP was observed over 24-hours. Infusion
      pumps with Dulbecco's Modified Eagle Medium (DMEM) simulated a constant aqueous
      humor circulation. A histological examination of the trabecular meshwork with
      DAPI- and TUNEL-staining was performed to detect the amount of apoptotic cells.
      RESULTS: TUNEL-assay showed a mean cell death rate of 3.78% (SD +/- 1.46%) for
      silicone oil endotamponades compared to 5.05% (SD +/- 2.18%) in BSS group. One
      way ANOVA (p = 0.425) showed no significant difference between both groups. Mean
      IOP in silicone oil endotamponades was 9.50 mmHg (SD +/- 1.68 mmHg) at baseline,
      13.23 mmHg (SD +/- 0.79 mmHg) after 1 hour, 18.46 mmHg (SD +/- 2.13 mmHg) after
      12 hours and 15.51 mmHg (SD +/- 2.82 mmHg) 24 hours after instillation. A
      comparison of all silicone oil groups (one-way ANOVA, Bonferroni post-hoc test, p
      = 0.269 to 1.000) didn't reveal significant differences in mean IOP. CONCLUSION:
      The standardized ex-vivo porcine model represents an effective alternative to the
      in-vivo testing in animals. Maintaining the trabecular and uveoscleral outflow
      pathway enables a pseudo in-vivo analysis.

PMID- 28441063
TI  - Validating the psycholinguistic aspects of LITMUS-CLT: Evidence from Polish and
      Norwegian.
AB  - The novel assessment tool Cross-Linguistic Lexical Tasks (LITMUS-CLT) aims for
      comparable cross-linguistic assessment of multilingual children's lexical skills
      by basing each language version on two language-specific variables: age of
      acquisition (AoA) and complexity index (CI), a novel measure related to
      phonology, morphology, exposure and etymology. This article investigates the
      validity of this methodology, asking whether the underlying properties are robust
      predictors of children's performance. The Polish and Norwegian CLTs were used to
      assess 32 bilingual Polish-Norwegian, 34 monolingual Norwegian and 36 monolingual
      Polish children. The effects of AoA and CI were contrasted with frequency in
      child directed speech (CDS) and imageability, two known predictors of lexical
      development. AoA was a reliable predictor of performance within all parts of CLT,
      in contrast to CI. Apart from AoA, only exposure and CDS frequency had a
      significant effect within both monolinguals and bilinguals. These results
      indicate that CLT assesses lexical skills in a cross-linguistically comparable
      manner, but suggest a revision of the CI measure.

PMID- 28441062
TI  - Measles cases among adolescents in southern Pakistan 2012-2015: The case for
      revisiting vaccination strategies.
AB  - AIMS: Surveillance of adult measles in Pakistan is a challenge as it does not
      enjoy the status of a reportable disease unlike childhood cases and therefore
      cases remain undetected and unreported or misdiagnosed. Consequently no data or
      estimates of young adult cases, seroprevalence, or estimates of susceptible
      preadolescent or young adult population exist. We have presented both laboratory
      conformed and clinically suspected cases of measles occurring in adolescents and
      adults in the southern province of Sindh in Pakistan. METHODS: Through an
      examination of 2 independent databases, i.e. a laboratory database of measles IgM
      positive cases and clinically detected cases on surveillance performed by the
      Disease Early Warning System, we have analyzed and reported age-specific
      positivity rates from 2012 to 2015 in Sindh, Pakistan. RESULTS: High rates of
      laboratory confirmed measles were observed in those aged 9 y and younger. Among
      adolescents and adults, significantly higher positivity rates were observed among
      those aged 10-19 y. Clinically detected cases from Sindh showed similar
      distribution of cases. CONCLUSIONS: High burden of cases among children <9 y of
      age confirm that supplementary immunization activities (SIAs) among this age
      group are inadequate and need to be strengthened. Cases among those 10-19 y
      further demonstrate the need for consolidating SIAs with an additional strategy
      to vaccinate those who remain non-immune at college entry and in institutions
      where outbreaks can be prevented. Such measures are essential to achieving the
      goal of measles elimination in the country and region.

PMID- 28441061
TI  - Precisely Where Are We Going? Charting the New Terrain of Precision Prevention.
AB  - In addition to genetic data, precision medicine research gathers information
      about three factors that modulate gene expression: lifestyles, environments, and
      communities. The relevant research tools-epidemiology, environmental assessment,
      and socioeconomic analysis-are those of public health sciences rather than
      molecular biology. Because these methods are designed to support inferences and
      interventions addressing population health, the aspirations of this research are
      expanding from individualized treatment toward precision prevention in public
      health. The purpose of this review is to explore the emerging goals and
      challenges of such a shift to help ensure that the genomics community and public
      policy makers understand the ethical issues at stake in embracing and pursuing
      precision prevention. Two emerging goals bear special attention in this regard:
      (a) public health risk reduction strategies, such as screening, and (b) the
      application of genomic variation studies to understand and reduce health
      disparities among population groups.

PMID- 28441064
TI  - Bacillus Calmette-Guerin alleviates airway inflammation and remodeling by
      preventing TGF-beta1 induced epithelial-mesenchymal transition.
AB  - Bacillus Calmette-Guerin (BCG) is a potent agent for the prevention of
      tuberculosis. Current studies have regarded BCG as an immunomodulator. However,
      there is little information on whether it can be used to inhibit airway
      inflammation and airway remodeling caused by asthma. Therefore, in this study, we
      investigate the role of epithelial-mesenchymal transition (EMT) in airway
      inflammation and airway remodeling as well as the possible therapeutic mechanism
      of BCG for the treatment of asthma. Wistar rats were sensitized and challenged by
      ovalbumin for 2 weeks or 8 weeks. BCG was subcutaneously administered daily
      before every ovalbumin challenge to determine its therapeutic effects. The 2
      weeks model group showed extensive eosinophilia, chronic inflammatory responses,
      bronchial wall thickening, airway epithelium damage, increased levels of
      transforming growth factor beta 1 (TGF-beta1) in both bronchoalveolar lavage
      fluid and sera, decreased expression of epithelial marker E-cadherin, and
      increased expressions of mesenchymal markers alpha-smooth muscle actin (alpha
      SMA) and Fibronectin (Fn). Except for inflammatory responses, all responses were
      more significant in the 8 weeks model group which displayed characteristics of
      airway remodeling including subepithelial fibrosis, smooth muscle hypertrophy,
      and goblet cell hyperplasia. When compared with the model groups, BCG
      administration inhibited airway inflammation and airway remodeling, decreased TGF
      beta1 levels, upregulated expression of E-cadherin, and downregulated expression
      of alpha-SMA and Fn. The present study suggests for the first time that increased
      secretion of TGF- beta1 induced by asthmatic chronic inflammation may result in
      EMT, which is one of the most important mechanisms of airway inflammation and
      airway remodeling seen with asthma. BCG alleviates airway inflammation and airway
      remodeling by preventing TGF-beta1 induced EMT, therefore BCG may be a new
      therapy for treating asthma.

PMID- 28441065
TI  - The Effect of Sterilization Methods of Endoscopic Instruments on the Body: A
      Study on Rat Model.
AB  - PURPOSE: Laparoscopy is widely used in many surgical areas for diagnosis and
      treatment. The need for sterilization of reusable instruments is an important
      issue. Ensuring patient safety, preventing infection, and protecting the
      functionality of the instruments are the most important points to be considered.
      We aimed to investigate two sterilization methods and their effects generated by
      their distribution into intra-abdominal tissues during insufflation. MATERIALS
      AND METHODS: 21 rats were used in the study. The Control Group (Group 1) received
      anesthesia for 1 hour; Group 2 (Glutaraldehyde (GA)-Pneumoperitoneum Group)
      received anesthesia for 1 hour; Group 3 (Ethylene Oxide (EO)-Pneumoperitoneum
      Group) received anesthesia for 1 hour. After 24 hours, the animals were
      sacrificed, and the kidneys and omentum of the animals were analyzed in a
      histopathological manner. Blood samples were analyzed at preoperative 24th hour
      and at postoperative 24th hour. RESULTS: There was a statistically significant
      difference in omentum, endothelium, and glomerular scores between the groups (p <
      0.001 for all groups). Endothelial and glomerular scores were different at a
      statistically significant level in the EO and GA groups compared to the Control
      Group. The total score was higher at a statistically significant level in the EO
      and GA groups compared to the Control Group (p < 0.001 for both groups).
      CONCLUSION: It was determined in our study that sterilization methods such as EO
      and GA cause damage in intra-abdominal tissues. In the light of these results, we
      consider that the most ideal laparoscopic surgery set is the single-use
      laparoscopy set. However, this does not seem possible especially in developing
      countries in practice.

PMID- 28441066
TI  - Continued Care in Palliative Bowel Surgery: An Invited Brief Commentary on "Long
      Term Functional Outcome After Internal Delorme's Procedure for Obstructed
      Defecation Syndrome and the Role of Post-Operative Rehabilitation".

PMID- 28441067
TI  - Anterior Segment Optical Coherence Tomography Angiography for Identification of
      Iris Vasculature and Staging of Iris Neovascularization: A Pilot Study.
AB  - : Purpose/Aim of the study: To assess the ability of optical coherence
      tomographic angiography (OCTA) to visualize the normal iris vasculature as well
      as neovascularization of the iris (NVI). MATERIALS AND METHODS: Study
      participants with healthy eyes, patients at risk of NVI development and patients
      with active or regressed NVI were consecutively included in this cross-sectional
      observational study. Imaging was performed using a commercially available OCTA
      system (RTVue- XR Avanti, Optovue Inc., Fremont, CA, USA). Abnormal iris vessels
      were graded on OCTA according to a modified clinical staging system and compared
      to slitlamp and gonioscopic findings. RESULTS: Fifty eyes of 26 study
      participants (16 healthy eyes, 19 eyes at risk, 15 eyes with different stages of
      NVI) were imaged using OCTA. In 11 out of 16 healthy eyes (69%) with light or
      moderately dark iris pigmentation, we observed physiological, radially aligned
      iris vasculature on OCTA imaging, which could not be visualized in five eyes
      (31%) with darkly pigmented irides. One eye in the "eyes at risk" group was
      diagnosed with NVI based on OCTA, which was not observed clinically. Fifteen eyes
      with clinically active or regressed NVI were imaged. Different stages of NVI
      could be differentiated by OCTA, corresponding well to an established clinical
      grading system. Four eyes showed regressed NVI by OCTA, not seen clinically, and
      were graded as a newly defined stage 4. CONCLUSIONS: This pilot clinical study
      showed that OCTA for imaging of the iris vasculature in health and disease is
      highly dependent on iris pigmentation. Fine, clinically invisible iris vessels
      can be visualized by OCTA in the very early stages as well as in the regressed
      stage of NVI.

PMID- 28441068
TI  - A Controlled, Randomized Double-Blind Study to Evaluate the Safety and Efficacy
      of Chitosan-N-Acetylcysteine for the Treatment of Dry Eye Syndrome.
AB  - PURPOSE: This study was designed to evaluate the effect of chitosan-N
      acetylcysteine (C-NAC) eye drops on tear film thickness (TFT) in patients with
      dry eye syndrome (DES). METHODS: This was a controlled, randomized, double-blind
      clinical investigation with patients assigned to 2 cohorts. In Cohort I, 21
      patients were randomized to receive 1 instillation of C-NAC eye drops in 1 eye
      and placebo (normal saline solution) in the contralateral eye. In Cohort II, 17
      patients were randomized to receive C-NAC eye drops once (QD) or twice (BID)
      daily for 5 days. TFT was assessed with a custom-built ultrahigh-resolution
      optical coherence tomography system. RESULTS: In Cohort I, mean TFT increased
      from 3.9 +/- 0.5 MUm predose to 4.8 +/- 1.1 MUm 10 min postdose after treatment
      with C-NAC. The increase was significantly different from placebo over time (P <
      0.0001) and remained stable until 24 h postdose. In Cohort II, TFT increased with
      QD and BID instillation, with no significant difference between regimens. In both
      groups, Ocular Surface Disease Index scores improved, fewer patients presented
      with corneal damage, and symptoms of ocular discomfort/conjunctival redness were
      reduced. CONCLUSIONS: A single instillation of C-NAC significantly increased mean
      TFT in patients with DES as early as 10 min after instillation and lasted for 24
      h. The magnitude of the increase in TFT following a single instillation was
      comparable with that after instillation twice daily over 5 days. Corneal damage
      improved in >60% of patients. C-NAC could be a viable treatment option for DES.

PMID- 28441069
TI  - Low doses of IgG from atopic individuals can modulate in vitro IFN-gamma
      production by human intra-thymic TCD4 and TCD8 cells: An IVIg comparative
      approach.
AB  - The regulatory effect of allergic responses induced by IgG antibodies on human
      intra-thymic cells has not been reported in the literature. The aim of this study
      was to evaluate the possible differential effect of purified IgG from atopic and
      non-atopic individuals on human intra-thymic alphabetaT cell cytokine production.
      Thymic tissues were obtained from 14 patients who were less than 7 d old.
      Additionally, blood samples were collected from atopic and non-atopic volunteers.
      Thymocytes and peripheral blood mononuclear cells were cultured with purified
      atopic or non-atopic IgG, and intracellular cytokine production was assessed.
      Purified IgG did not influence the frequency or viability of human intra-thymic
      alphabetaT cells. Purified non-atopic IgG induced greater IFN-gamma production by
      intra-thymic CD4+CD8+ T cells than did the mock treatment and atopic IgG. A
      similar effect of purified non-atopic IgG on TCD8 cells was observed compared
      with the mock treatment. Atopic IgG inhibited IFN-gamma and TGF-beta production
      by intra-thymic TCD4 cells. Treatment with intravenous immunoglobulin resulted in
      intermediate levels of IFN-gamma and TGF-beta in intra-thymic TCD4 cells compared
      with treatment with atopic and non-atopic IgG. Peripheral TCD4 cells from non
      atopic individuals produced IFN-gamma only in response to atopic IgG. This report
      describes novel evidence revealing that IgG from atopic individuals may influence
      intracellular IFN-gamma production by intra-thymic alphabetaT cells in a manner
      that may favor allergy development.

PMID- 28441070
TI  - The Thr300Ala variant of ATG16L1 is associated with decreased risk of brain
      metastasis in patients with non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but
      identifying which patients will develop brain metastases (BM) is difficult.
      Macroautophagy/autophagy is critical for cancer initiation and progression. We
      hypothesized that genetic variants of autophagy-related genes may affect brain
      metastases (BM) in NSCLC patients. We genotyped 16 single nucleotide
      polymorphisms (SNPs) in 7 autophagy-related (ATG) genes (ATG3, ATG5, ATG7, ATG10,
      ATG12, ATG16L1, and MAP1LC3/LC3) by using DNA from blood samples of 323 NSCLC
      patients. Further, we evaluated the potential associations of these genes with
      subsequent BM development. Lung cancer cell lines stably transfected with
      ATG16L1: rs2241880 (T300A) were established. Mouse models of brain metastasis
      were developed using cells transfected with ATG16L1-300T or ATG16L1-300A. ATG10:
      rs10036653 and ATG16L1: rs2241880 were significantly associated with a decreased
      risk of BM (respective hazard ratios [HRs]=0.596, 95% confidence interval [CI]
      0.398-0.894, P = 0.012; and HR = 0. 655, 95% CI 0.438-0.978, P = 0.039,
      respectively). ATG12: rs26532 was significantly associated with an increased risk
      of BM (HR=1.644, 95% CI 1.049-2.576, P = 0.030). Invasion and migration assays
      indicated that transfection with ATG16L1-300T (vs. 300A) stimulated the migration
      of A549 cells. An in vivo metastasis assay revealed that transfection with
      ATG16L1-300T (vs. 300A) significantly increased brain metastasis. Our results
      indicate that genetic variations in autophagy-related genes can predict BM and
      that genome analysis would facilitate stratification of patients for BM
      prevention trials.

PMID- 28441071
TI  - Efficacy and Safety of 23-Gauge Pars Plana Vitrectomy/Silicone Oil Tamponade
      Combination for Treatment of Pediatric Post-Traumatic Endophthalmitis.
AB  - PURPOSE: To determine (i) the etiology, epidemiology, mechanism of injury, and
      risk factors associated with open globe injuries (OGIs) in children and (ii)
      visual outcomes of pediatric patients with post-traumatic endophthalmitis
      following 23-gauge pars plana vitrectomy (PPV) combined with silicone oil
      tamponade (SOT). METHODS: A total of 107 consecutive patients, <15 years of age,
      who had been diagnosed with post-traumatic endophthalmitis between September 2009
      and October 2015, were included in this 6-year retrospective study. All patients
      had undergone a combined PPV and SOT procedure. We reviewed records and analyzed
      several parameters, including age, gender, wound anatomy, intraocular foreign
      body characteristics, best-corrected visual acuity (BCVA), and anatomic re
      attachment of the vitreous. Visual acuity (VA) was evaluated by comparing the
      Ocular Trauma Scores (OTS) system with BCVA (as assessed by Fisher's exact test).
      RESULTS: Patients included 70 (65.42%) boys and 37 (34.58%) girls (mean, 7.84 +/-
      2.31 years). Mean follow-up time was 13.31 +/- 3.15 months. Zone-1 injuries
      accounted for 15 of 107 (14.02%) cases, while Zones-2 and -3 accounted for 69 of
      107 (64.49%), and 23 of 107 (21.50%) cases, respectively. Lens trauma was noted
      in 53 of 107 (49.53%) eyes. Our analysis showed that the 6-month BCVA, as
      assessed by OTS, differed significantly between groups OTS-1 (p = 0.001) and OTS
      2 (p = 0.012). No significant difference was observed in group OST-3 (p = 1.000).
      Total retinal attachment was achieved in 99 of 107 eyes (92.52%). CONCLUSIONS:
      Following combined PPV/SOT for post-traumatic endophthalmitis, VAs were not only
      favorable, but also often better than those predicted by OTS. Increased awareness
      of the very serious nature of endophthalmitis is expected to help in the
      development of a comprehensive strategy designed to educate both parents and
      children, and to minimize the number of preventable pediatric OGIs.

PMID- 28441073
TI  - Orbital and conjunctival metastasis from lobular breast carcinoma.
AB  - This article examines the clinical presentation of ocular metastasis from an
      infiltrating lobular breast carcinoma. We examined a conjunctival biopsy from a
      69-year-old woman who developed unilateral conjunctival inflammation together
      with a neurotrophic corneal ulcer and proptosis. Infiltrating lobular breast
      carcinoma (ILBC) was diagnosed using routine histology and immunohistochemistry.
      She had a past history of a hormone receptor-positive infiltrating ILBC 11 years
      ago with cutaneous and diffuse osteoblastic metastases, and she was kept under
      treatment with lezotrol. Treatment was initiated with systemic corticosteroids
      but an annular conjunctival perilimbal infiltration was found to have spread,
      which did not respond either to local radiotherapy (total dose 60 Gy, 2 Gy per
      day). A new extensive corneal epithelial defect recurred, and because it had not
      responded to matrix therapy agent (RGTA, Cacicol(r)) eye drops, autologous serum
      eye drops and a therapeutic contact lens, a permanent total tarsorrhaphy was
      performed. Progression of the diffuse bone metastases was detected and the
      treatment with lezotrol was replaced by fulvestrant.Infiltrating lobular breast
      carcinoma is a rare cause of conjunctival metastasis. This aggressive malignancy
      did not respond to external beam radiotherapy.

PMID- 28441072
TI  - Pro-tumor activities of macrophages in the progression of melanoma.
AB  - Macrophages are located in essentially all tissues due to their "janitor"
      function. Macrophages can exert either anti- or pro-tumor activities depending
      upon the specific tumor microenvironment they inhabit. Substantial evidence
      indicates that macrophages, owing to their plasticity, can be reeducated to adopt
      a protumoral phenotype within a tumor microenvironment through the help of growth
      factors in the microenvironment and intercellular interactions. As the lethality
      of malignant melanoma is due to its aggressive capacity for metastasis and
      resistance to therapy, considerable effort has gone toward treatment of
      metastatic melanoma. In the present review, we focus on the pro-tumor activities
      of macrophages in melanoma. Based upon the information presented in this review
      it is anticipated that new therapies will soon be developed that target pro-tumor
      activities of macrophages for use in the treatment of melanoma.

PMID- 28441074
TI  - Assessing Lebanese bilingual children: The use of Cross-linguistic Lexical Tasks
      in Lebanese Arabic.
AB  - Since norms for vocabulary acquisition in Lebanese bilingual children (L1:
      Lebanese, L2: French and/or English) do not yet exist, clinical assessment based
      on normative data and using appropriate tools remains difficult for speech and
      language therapists. The current study focuses on exploring and comparing lexical
      performances of typically developing Lebanese bilingual children (32 Bi-TD, aged
      5;7 to 6;9) and those with specific language impairment (10 Bi-SLI, aged 5;9 to
      7;10), using Cross-Linguistic Lexical Tasks (LITMUS-CLT, COST Action IS0804,
      2011) in Lebanese Arabic language (CLT-LB), specific to the Lebanese context. The
      results confirm that typically developing children have better lexical skills,
      especially expressive skills, than their peers with specific language impairment.
      Expressive and receptive performance by both groups of children was found to
      depend on word class (nouns and verbs). Bi-TD children were more accurate at
      naming and recognising verbs than the Bi-SLI group. The results of these lexical
      tasks reveal aspects of the nature of bilingual lexical variation, as well as
      similarities and differences between the Bi-TD and Bi-SLI groups.

PMID- 28441075
TI  - Autophagy and kidney inflammation.
AB  - Inflammation plays a pivotal role in pathophysiological processes of kidney
      diseases. Macroautophagy/autophagy plays multiple roles in inflammatory
      responses, and the regulation of inflammation by autophagy has great potential as
      a treatment for damaged kidneys. A growing body of evidence suggests autophagy
      protects kidney from versatile kidney inflammatory insults, including those that
      are acute, chronic, metabolic, and aging-related. It is noteworthy that, in
      kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In
      this mode, autophagy suppresses inflammation to protect the kidney. Systemic
      inflammation also affects the kidney via pro-inflammatory cytokines and
      infiltration of inflammatory cells, and autophagy also has a regulatory role in
      systemic inflammation. This review focuses on the roles of autophagy in kidney
      diseases and aging through inflammation, and discusses the potential usage of
      autophagy as an inflammatory modulator for the treatment of kidney diseases.

PMID- 28441076
TI  - A Novel Neuroprotective Small Molecule for Glial Cell Derived Neurotrophic Factor
      Induction and Photoreceptor Rescue.
AB  - PURPOSE: Degenerative diseases of the retina, such as retinitis pigmentosa and
      age-related macular degeneration, are characterized by the irreversible loss of
      photoreceptors. Several growth factors, including glial cell derived neurotrophic
      factor (GDNF), have been shown to rescue retinal neurons. An alternative strategy
      to direct GDNF administration is its induction in host retina by small molecules.
      Here we studied the ability of a novel small molecule GSK812 to induce GDNF in
      vitro/in vivo and rescue photoreceptors. METHODS: GDNF induction in vitro was
      assessed in human ARPE-19, human retinal progenitor cells (RPCs) and mouse
      pluripotent cell-derived eyecups. For time course pharmacokinetic and GDNF
      induction studies in C57Bl/6 mice, GSK812 sustained release formulation was
      injected intravitreally. The same delivery approach was used in the rhodopsin
      knockout mice and Royal College of Surgeon (RCS) rats to assess long-term GDNF
      induction and photoreceptor rescue. RESULTS: The suspension provided sustained
      GSK812 delivery with 28 MUg of drug remaining in the eye 2 weeks after a single
      injection. GSK812 suspension injection in C57Bl/6 mice resulted in significant
      upregulation of GDNF mRNA (>1.8-fold) and protein levels (>2.8-fold).
      Importantly, GSK812 treatment resulted in outer nuclear layer preservation in rho
      /- mice with a 2-fold difference in photoreceptor number. In the RCS rat, the
      GSK812 injection provided long-term rescue of photoreceptors and outer segments,
      accompanied by function preservation as well. CONCLUSIONS: GSK812 is a potent
      neuroprotectant that can induce GDNF in normal and diseased retina. This
      induction results in photoreceptor rescue in 2 models of retinal degeneration.

PMID- 28441077
TI  - Comparison of Conbercept with Ranibizumab for the Treatment of Macular Edema
      Secondary to Branch Retinal Vein Occlusion.
AB  - PURPOSE: To confirm the therapeutic efficacy of conbercept for the treatment of
      macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: In
      this prospective, randomized, and comparative study, patients were randomized and
      divided into conbercept (n = 18) and ranibizumab (n = 17) groups. After an
      initial intravitreal injection of either conbercept or ranibizumab, a pro re nata
      (PRN) strategy was adopted based on loss of visual acuity (VA) or increase in
      central macular thickness (CMT). RESULTS: All patients were followed for >=6
      months. Baseline best-corrected visual acuities (BCVAs) were 0.67 +/- 0.37 and
      0.511 +/- 0.23 logMAR in the conbercept and ranibizumab groups, respectively (p =
      0.087, t-test). Baseline CMTs were 512.5 +/- 115.22 and 491.23 +/- 114.72 um in
      the conbercept and ranibizumab groups, respectively (p = 0.993, t-test).
      Significant improvements in BCVA and reduction of CMT were observed in both
      groups at each follow-up visit and compared to baseline values (p < 0.05, t
      test). No significant differences in improvement of BCVA (p > 0.05, t-test) or
      reduction of CMT (p > 0.05, t-test) were noted in either group. Mean numbers of
      injections were 2.28 +/- 0.96 and 2.65 +/- 1.17 for the conbercept and
      ranibizumab groups, respectively (p = 0.478, t-test), with no statistically
      significant differences between the two groups. CONCLUSION: Intravitreal
      injection of conbercept is shown to be safe and effective for the treatment of ME
      secondary to BRVO, based on 6-month follow-up data.

PMID- 28441078
TI  - Comparison of 0.3% Hypotonic and Isotonic Sodium Hyaluronate Eye Drops in the
      Treatment of Experimental Dry Eye.
AB  - PURPOSE: To compare the efficacy of 0.3% hypotonic and isotonic sodium
      hyaluronate (SH) eye drops in the treatment of experimental dry eye. METHODS:
      Experimental dry eye was established in female C57BL/6 mice by subcutaneous
      scopolamine injection and an air draft. The mice were divided into three groups
      (n = 15): control, preservative-free 0.3% isotonic SH, and preservative-free 0.3%
      hypotonic SH. The tear volume, tear film break-up time, and corneal fluorescein
      staining scores were measured 5 and 10 days after treatment. After conjunctival
      tissues were excised at 10 days, the levels of interleukin (IL)-6, IL-17,
      interferon (IFN)-gamma, and IFN-gamma inducible protein-10 were determined using
      the multiplex immunobead assay. In addition, PAS staining and flow cytometry were
      performed to evaluate the counts of conjunctival goblet cells and CD4+ IFN-gamma+
      T cells. RESULTS: Mice treated with 0.3% hypotonic SH showed a significant
      decrease in corneal staining scores (P = 0.04) and the levels of IL-6 (16.7 +/-
      1.4 pg/mL, P = 0.02) and IFN-gamma (46.5 +/- 11.5 pg/mL, P = 0.02) compared to
      mice treated with 0.3% isotonic SH (IL-6; 32.5 +/- 8.8 pg/mL, IFN-gamma; 92.0 +/-
      16.0 pg/mL) at day 10. Although no significant difference in CD4+ IFN-gamma+ T
      cell numbers was observed, goblet cell counts were higher in the hyopotonic SH
      group than in the isotonic SH group (P = 0.02). CONCLUSIONS: When compared to
      0.3% isotonic SH eye drops, 0.3% hypotonic SH eye drops can be more effective by
      improving corneal staining scores, decreasing inflammatory molecules, and
      increasing goblet cell counts for experimental dry eye. These data suggest that
      hypotonic artificial tears may be useful as an adjunctive treatment for
      inflammatory dry eye.

PMID- 28441079
TI  - The vocabulary profile of Slovak children with primary language impairment
      compared to typically developing Slovak children measured by LITMUS-CLT.
AB  - This study compared a sample of children with primary language impairment (PLI)
      and typically developing age-matched children using the crosslinguistic lexical
      tasks (CLT-SK). We also compared the PLI children with typically developing
      language-matched younger children who were matched on the basis of receptive
      vocabulary. Overall, statistical testing showed that the vocabulary of the PLI
      children was significantly different from the vocabulary of the age-matched
      children, but not statistically different from the younger children who were
      matched on the basis of their receptive vocabulary size. Qualitative analysis of
      the correct answers revealed that the PLI children showed higher rigidity
      compared to the younger language-matched children who are able to use more
      synonyms or derivations across word class in naming tasks. Similarly, an
      examination of the children's naming errors indicated that the language-matched
      children exhibited more semantic errors, whereas PLI children showed more
      associative errors.

PMID- 28441081
TI  - Comparison of Size Modulation Standard Automated Perimetry and Conventional
      Standard Automated Perimetry with a 10-2 Test Program in Glaucoma Patients.
AB  - PURPOSE: This prospective observational study compared the performance of size
      modulation standard automated perimetry with the Octopus 600 10-2 test program,
      with stimulus size modulation during testing, based on stimulus intensity and
      conventional standard automated perimetry, with that of the Humphrey 10-2 test
      program in glaucoma patients. METHODS: Eighty-seven eyes of 87 glaucoma patients
      underwent size modulation standard automated perimetry with Dynamic strategy and
      conventional standard automated perimetry using the SITA standard strategy. The
      main outcome measures were global indices, point-wise threshold, visual defect
      size and depth, reliability indices, and test duration; these were compared
      between size modulation standard automated perimetry and conventional standard
      automated perimetry. RESULTS: Global indices and point-wise threshold values
      between size modulation standard automated perimetry and conventional standard
      automated perimetry were moderately to strongly correlated (p < 0.01). However,
      the correlation coefficient of point-wise threshold value for the central zone
      was significantly lower than that for the peripheral zone (chi2 > 33.40, p <
      0.01). Better mean defect and point-wise threshold values were obtained with size
      modulation standard automated perimetry than with conventional standard automated
      perimetry, but the visual-field defect size was smaller (p < 0.01) and depth
      shallower (p < 0.01) on size modulation-standard automated perimetry than on
      conventional standard automated perimetry. The reliability indices, particularly
      the false-negative response, of size modulation standard automated perimetry were
      worse than those of conventional standard automated perimetry (p < 0.01). The
      test duration was 6.5% shorter with size modulation standard automated perimetry
      than with conventional standard automated perimetry (p = 0.02). CONCLUSIONS:
      Global indices and the point-wise threshold value of the two testing modalities
      correlated well. However, the potential of a large stimulus presented at an area
      with a decreased sensitivity with size modulation standard automated perimetry
      could underestimate the actual threshold in the 10-2 test protocol, as compared
      with conventional standard automated perimetry.

PMID- 28441080
TI  - Color-coded intravital imaging demonstrates a transforming growth factor-beta
      (TGF-beta) antagonist selectively targets stromal cells in a human pancreatic
      cancer orthotopic mouse model.
AB  - Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma
      which stimulates tumor growth, invasion, and metastasis, and inhibits
      chemotherapeutic drug delivery. Transforming growth factor-beta (TGF-beta) has an
      important role in the formation of stromal desmoplasia. The present study
      describes the ability of color-coded intravital imaging to demonstrate the
      efficacy of a TGF-beta inhibitor to target stroma in an orthotopic mouse model of
      pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line
      expressing green fluorescent protein (GFP), which also has a high TGF-beta
      expression level, was used in an orthotopic model in transgenic nude mice
      ubiquitously expressing red fluorescent protein (RFP). Fourteen mice were
      randomized into a control group (n = 7, vehicle, i.p., weekly, for 3 weeks) and a
      treated group (n = 7, SB431542 [TGF-beta receptor type I inhibitor] 0.3 mg, i.p.,
      weekly, for 3 weeks). Stromal cells expressing RFP and cancer cells expressing
      GFP were observed weekly for 3 weeks by real-time color-coded intravital imaging.
      The RFP fluorescence area from the stromal cells, relative to the GFP
      fluorescence area of the cancer cells, was significantly decreased in the TGF
      beta-inhibitor-treatment group compared to the control group. The present study
      demonstrated color-coded imaging in an orthotopic pancreatic-cancer cell-line
      mouse model can readily detect the selective anti-stromal-cell targeting of a TGF
      beta inhibitor.

PMID- 28441082
TI  - Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stages I to IIIA
      Resectable Non-Small-Cell Lung Cancers: American Society of Clinical
      Oncology/Cancer Care Ontario Clinical Practice Guideline Update Summary.

PMID- 28441083
TI  - Eyes on New Product Development.

PMID- 28441085
TI  - Noun and verb knowledge in monolingual preschool children across 17 languages:
      Data from Cross-linguistic Lexical Tasks (LITMUS-CLT).
AB  - This article investigates the cross-linguistic comparability of the newly
      developed lexical assessment tool Cross-linguistic Lexical Tasks (LITMUS-CLT).
      LITMUS-CLT is a part the Language Impairment Testing in Multilingual Settings
      (LITMUS) battery (Armon-Lotem, de Jong & Meir, 2015). Here we analyse results on
      receptive and expressive word knowledge tasks for nouns and verbs across 17
      languages from eight different language families: Baltic (Lithuanian), Bantu
      (isiXhosa), Finnic (Finnish), Germanic (Afrikaans, British English, South African
      English, German, Luxembourgish, Norwegian, Swedish), Romance (Catalan, Italian),
      Semitic (Hebrew), Slavic (Polish, Serbian, Slovak) and Turkic (Turkish). The
      participants were 639 monolingual children aged 3;0-6;11 living in 15 different
      countries. Differences in vocabulary size were small between 16 of the languages;
      but isiXhosa-speaking children knew significantly fewer words than speakers of
      the other languages. There was a robust effect of word class: accuracy was higher
      for nouns than verbs. Furthermore, comprehension was more advanced than
      production. Results are discussed in the context of cross-linguistic comparisons
      of lexical development in monolingual and bilingual populations.

PMID- 28441086
TI  - Hematopoietic-to-mesenchymal transition of adipose tissue macrophages is
      regulated by integrin beta1 and fabricated fibrin matrices.
AB  - Some bona fide adult adipocytes arise de novo from a bone marrow-derived myeloid
      lineage. These studies further demonstrate that adipose tissue stroma contains a
      resident population of myeloid cells capable of adipocyte and multilineage
      mesenchymal differentiation. These resident myeloid cells lack hematopoietic
      markers and express mesenchymal and progenitor cell markers. Because bone marrow
      mesenchymal progenitor cells have not been shown to enter the circulation, we
      hypothesized that myeloid cells acquire mesenchymal differentiation capacity in
      adipose tissue. We fabricated a 3-dimensional fibrin matrix culture system to
      define the adipose differentiation potential of adipose tissue-resident myeloid
      subpopulations, including macrophages, granulocytes and dendritic cells. Our data
      show that multilineage mesenchymal potential was limited to adipose tissue
      macrophages, characterized by the acquisition of adipocyte, osteoblast,
      chondrocyte and skeletal muscle myocyte phenotypes. Fibrin hydrogel matrices
      stimulated macrophage loss of hematopoietic cell lineage determinants and the
      expression of mesenchymal and progenitor cell markers, including integrin beta1.
      Ablation of integrin beta1 in macrophages inhibited adipocyte specification.
      Therefore, some bona fide adipocytes are specifically derived from adipose tissue
      resident macrophages via an integrin beta1-dependent hematopoietic-to-mesenchymal
      transition, whereby they become capable of multipotent mesenchymal
      differentiation. The requirement for integrin beta1 highlights this molecule as a
      potential target for controlling the production of marrow-derived adipocytes and
      their contribution to adipose tissue development and function.

PMID- 28441087
TI  - Using the Payoff Time in Decision-Analytic Models: A Case Study for Using Statins
      in Primary Prevention.
AB  - BACKGROUND: The payoff time represents an estimate of when the benefits of an
      intervention outweigh the costs. It is particularly useful for benefit-harm
      decision making for interventions that have deferred benefits but upfront harms.
      The aim of this study was to expand the application of the payoff time and
      provide an example of its use within a decision-analytic model. METHODS: Three
      clinically relevant patient vignettes based on varying levels of estimated 10
      year cardiovascular risk (10%, 15%, 20%) were developed. An existing state
      transition Markov model taking a health service perspective and a life-time
      horizon was adapted to include 3 levels of direct treatment disutility (DTD)
      associated with ongoing statin use: 0.005, 0.01, and 0.015. For each vignette and
      DTD we calculated a range of outputs including the payoff time inclusive and
      exclusive of healthcare costs. RESULTS: For a 10% 10-year cardiovascular risk
      (vignette 1) with low-levels of DTD (0.005), the payoff time was 8.5 years when
      costs were excluded and 16 years when costs were included. As the baseline risk
      of cardiovascular increased, the payoff time shortened. For a 15% cardiovascular
      risk (vignette 2) and for a low-level of DTD, the payoff time was 5.5 years and
      9.5 years, respectively. For a 20% cardiovascular risk (vignette 3), the payoff
      time was 4.2 and 7.2 years, respectively. For higher levels of DTDs for each
      vignette, the payoff time lengthened, and in some instances the intervention
      never paid off, leading to an expected net harm for patients. CONCLUSIONS: This
      study has shown how the payoff time can be readily applied to an existing
      decision-analytic model and be used to complement existing measures to guide
      healthcare decision making.

PMID- 28441088
TI  - Video-enabled cue-exposure-based intervention improves postdischarge drinking
      outcomes among alcohol-dependent men: A prospective study at a government
      addiction treatment setting in India.
AB  - Returning to alcohol use following inpatient treatment occurs due to various real
      life cues/triggers. It is a challenge to demonstrate to patients how to deal with
      these triggers during inpatient treatment. Aims of the current study were (a) to
      evaluate the effectiveness of video-enabled cue-exposure-based intervention (VE
      CEI) in influencing treatment outcomes in alcohol dependence, (b) to identify
      postdischarge predictors of intervention failure (returning to >=50% of baseline
      alcohol consumption quantity/day). The VE-CEI comprises live action videos in
      which human characters model various alcohol use cues and strategies to deal with
      them effectively. The VE-CEI was administered to an inpatient alcohol-dependent
      sample (n = 43) and compared with treatment as usual (TAU) (n = 42) at a
      government addiction treatment setting in India. Patients were followed up over 6
      months postdischarge to evaluate effectiveness of the VE-CEI on specific drinking
      outcomes. Over 6-month follow-up, VE-CEI group (vs. TAU) reported significantly
      lesser alcohol consumption quantity, fewer drinking days, and lower intervention
      failure rates. Results of multivariate Cox regression showed that participants
      who did not receive VE-CEI had an elevated risk of intervention failure (hazards
      ratio: 11.14; 95% confidence interval [4.93, 25.15]), other intervention failure
      predictors being early-onset dependence and increased baseline drinking. Findings
      provide evidence from India for effectiveness of cue-exposure-based intervention
      delivered using video technology in improving postdischarge treatment outcomes.

PMID- 28441084
TI  - The emergence of noncoding RNAs as Heracles in autophagy.
AB  - Macroautophagy/autophagy is a catabolic process that is widely found in nature.
      Over the past few decades, mounting evidence has indicated that noncoding RNAs,
      ranging from small noncoding RNAs to long noncoding RNAs (lncRNAs) and even
      circular RNAs (circRNAs), mediate the transcriptional and post-transcriptional
      regulation of autophagy-related genes by participating in autophagy regulatory
      networks. The differential expression of noncoding RNAs affects autophagy levels
      at different physiological and pathological stages, including embryonic
      proliferation and differentiation, cellular senescence, and even diseases such as
      cancer. We summarize the current knowledge regarding noncoding RNA dysregulation
      in autophagy and investigate the molecular regulatory mechanisms underlying
      noncoding RNA involvement in autophagy regulatory networks. Then, we integrate
      public resources to predict autophagy-related noncoding RNAs across species and
      discuss strategies for and the challenges of identifying autophagy-related
      noncoding RNAs. This article will deepen our understanding of the relationship
      between noncoding RNAs and autophagy, and provide new insights to specifically
      target noncoding RNAs in autophagy-associated therapeutic strategies.

PMID- 28441089
TI  - One size fits all? Antibody avidity measurement against multiple antigens in
      maternal vaccination studies.

PMID- 28441090
TI  - Religious involvement and marijuana use among a sample of African American young
      adults.
AB  - Is religiosity associated with African American drug use? Despite the increased
      research attention that has been devoted to the topic, findings to date have been
      inconclusive. To address this issue, we analyze data from a sample of 434 young
      adults residing in Miami-Dade County Florida. We find that, of the four
      dimensions of religiosity considered here, only religious attendance is inversely
      related to marijuana use for men and women. The implications of these findings
      are discussed.

PMID- 28441091
TI  - Siblings and the Coming-Out Process: A Comparative Case Study.
AB  - Siblings play a key, supportive role in the lives of many lesbian and gay adults.
      Yet siblings are rarely considered in the literature regarding the coming-out
      process (D'Augelli et al., 1998; Hilton & Szymanski, 2011; LaSala, 2010; Savin
      Williams & Dube, 1998). To fill this gap in the research literature, we carried
      out a comparative case study in the country of Belgium between two sets of
      siblings-three Romani brothers with one sibling identifying as a gay male and
      three White sisters with one sibling identifying as a lesbian. These two cases
      were pulled from a larger qualitative study (Haxhe & D'Amore, 2014) of 102 native
      French-speaking Belgian participants. Findings of the present study revealed that
      siblings offered critical socio-emotional support in the coming out of their
      lesbian and gay sibling, particularly with disclosing to parents and with
      fostering self-acceptance.

PMID- 28441092
TI  - Self-Evaluation of Quality of Life Among Patients Receiving Home Parenteral
      Nutrition: A Validation Study.
AB  - BACKGROUND: Home parenteral nutrition (HPN) can increase survival and quality of
      life (QOL) in cases of chronic intestinal failure. The present study compares a
      gold standard-a validated QOL assessment by Baxter et al (hereafter, HPN-QOL)
      with a shorter questionnaire for QOL evaluation (hereafter, New QOL). MATERIALS
      AND METHODS: Both questionnaires were completed by 58 patients attending the
      nutrition clinic of the Rabin Medical Center (Israel). A z score was used to
      equate means and variances. Statistical analysis was based on Pearson correlation
      between variances. Stepwise regression was used to evaluate the best value
      predictor in the New QOL for QOL during HPN. Cronbach's alpha was used for
      internal consistency, and confirmatory factor analysis was used for structural
      validity. RESULTS: Results from the sections of the New QOL that relate to the
      patient's general health, level of independence, and experience with handling the
      parenteral nutrition therapy are highly correlated with the HPN-QOL ( r = 0.43
      and r = 0.50, respectively). In addition, there was good correlation between the
      questionnaires with reference to the patient's social state, mental state, and
      everyday functioning ( r = -0.43, New QOL; r = -0.39, HPN-QOL). However, the New
      QOL results show no correlation between the patient's physical symptoms and QOL
      during HPN. This was hypothesized to result from the nature of the study
      population. CONCLUSION: The results of our new questionnaire are well correlated
      with the gold standard HPN-QOL. The New QOL appears to be simple and easy to use.

PMID- 28441093
TI  - Catching the evader: Can monoclonal antibodies interfere with Staphylococcus
      aureus immune escape?

PMID- 28441094
TI  - Background rates of disease in Latin American children from a rotavirus vaccine
      study.
AB  - BACKGROUND: Knowledge of background rates of adverse events is crucial to assess
      vaccine safety concerns. We used data from a rotavirus vaccine study (Ruiz
      Palacios et al., NEJM, 2006) including 63,225 infants from 11 Latin American
      countries to investigate reporting rates of serious adverse events (SAEs) among
      these infants, and describe rates by country, gender, age, and season. METHODS:
      For this randomized, double-blind, placebo-controlled, phase 3 trial,
      investigators from Argentina, Brazil, Chile, Colombia, Dominican Republic,
      Honduras, Mexico, Nicaragua, Panama, Peru, and Venezuela recruited 6-to-13-week
      old healthy infants. The infants received 2 oral doses of vaccine or placebo. The
      study population was followed 100 d for the assessment of adverse events. SAEs
      were captured by an active surveillance system. RESULTS: Strong differences in
      event rates could be observed between countries (min. 48.1/10,000 person-years in
      Dominican Republic/Peru; max. 296.2/10,000 person-years in Brazil) and between
      genders: gastroenteritis, pneumonia, bronchiolitis and bronchitis occurred
      significantly more frequently in males. In addition, infections and infestations,
      and most disorders, including immune system and cardiac disorders, were more
      frequent at earlier ages. Finally, looking at seasonality we noted higher rates
      of SAEs in the second half of the year in all countries except Mexico.
      DISCUSSION: Significant differences in reporting rates of SAEs between countries,
      gender and calendar months illustrate the importance of knowing the local
      epidemiology when interpreting SAEs. Data from clinical trials can be used to
      better understand background rates of diseases that may be perceived as potential
      adverse events following immunization.

PMID- 28441095
TI  - Perceived Harms and Social Norms in the Use of Electronic Cigarettes and
      Smokeless Tobacco.
AB  - Perceptions of harms and social norms influence the use of conventional tobacco
      cigarettes, but little research is available about their combined relationship
      with e-cigarette and smokeless tobacco use. We conducted a cross-sectional survey
      of 309 individuals from central Illinois. We explored (1) demographic predictors
      of perceived harms and social norms related to e-cigarette and smokeless tobacco
      use, and (2) whether perceived harms, social norms, or both were important
      predictors of e-cigarette and smokeless tobacco use. E-cigarette perceptions of
      harm were consistent across all demographic characteristics. Smokeless tobacco
      perceptions of harm were unrelated to age, race, and sex, but lower education and
      income were associated with lower perceived harm (p < .05). E-cigarette social
      norms were less favorable among non-whites (p < .05) but did not vary by other
      demographic characteristics. Only less education was associated with more
      favorable social norms of smokeless tobacco (p < .05). Higher perceived harms
      were related to lower use of e-cigarettes and smokeless tobacco (p < .05).
      Perceived social norms were not associated with product use. This study provides
      preliminary support for implementing broad-based health messaging efforts that
      focus more on the potential harms of e-cigarette and smokeless tobacco use than
      on social norms.

PMID- 28441096
TI  - Judicial Decision-Making and Juvenile Offenders: Effects of Medical Evidence and
      Victim Age.
AB  - A growing body of evidence suggests that jurors place greater weight on DNA or
      other types of forensic evidence than non-forensic evidence (Cole & Dioso-Villa,
      2009). For cases involving child sexual abuse, certain types of evidence,
      including forensic medical evidence, may be viewed as more important or
      indicative of abuse than other types of evidence, such as victim statements or
      disclosure. The present study evaluated perceptions of juvenile offenders and
      victim credibility across four vignettes that systematically manipulated
      variables related to victim age and physical indicators of abuse. A sample of 636
      participants read vignettes and answered questions pertaining to the vignette.
      Participants also provided demographic information and responded to a series of
      items assessing participants' judicial decision-making strategies and outcomes.
      Broadly, the presence of medical evidence significantly influenced participants'
      decision-making across a variety of variables, including verdict outcome, verdict
      confidence, confidence that the victim was truthful, and determinations involving
      sex offender registration and notification requirements. The influence of medical
      evidence and victim age on perceptions and sentencing of juvenile sex offenders
      across these and additional outcome variables will be discussed.

PMID- 28441097
TI  - Antismoking Ads at the Point of Sale: The Influence of Ad Type and Context on Ad
      Reactions.
AB  - Efforts are underway to educate consumers about the dangers of smoking at the
      point of sale (POS). Research is limited about the efficacy of POS antismoking
      ads to guide campaign development. This study experimentally tests whether the
      type of antismoking ad and the context in which ads are viewed influence people's
      reactions to the ads. A national convenience sample of 7,812 adult current
      smokers and recent quitters was randomized to 1 of 39 conditions. Participants
      viewed one of the four types of antismoking ads (negative health consequences
      graphic, negative social consequences-intended emotive, benefits of quitting
      informational, benefits of quitting-graphic) in one of the three contexts (alone,
      next to a cigarette ad, POS tobacco display). We assessed participants' reactions
      to the ads, including perceived effectiveness, negative emotion, affective
      dissonance, and motivational reaction. Graphic ads elicited more negative emotion
      and affective dissonance than benefits of quitting ads. Graphic ads elicited
      higher perceived effectiveness and more affective dissonance than intended
      emotive ads. Antismoking ads fared best when viewed alone, and graphic ads were
      least influenced by the context in which they were viewed. These results suggest
      that in developing POS campaigns, it is important to consider the competitive pro
      tobacco context in which antismoking ads will be viewed.

PMID- 28441098
TI  - How Robust Are Value Judgments of Health Inequality Aversion? Testing for Framing
      and Cognitive Effects.
AB  - BACKGROUND: Empirical studies have found that members of the public are
      inequality averse and value health gains for disadvantaged groups with poor
      health many times more highly than gains for better off groups. However, these
      studies typically use abstract scenarios that involve unrealistically large
      reductions in health inequality and face-to-face survey administration. It is not
      known how robust these findings are to more realistic scenarios or anonymous
      online survey administration. METHODS: This study aimed to test the robustness of
      questionnaire estimates of inequality aversion by comparing the following: 1)
      small versus unrealistically large health inequality reductions, 2) population
      level versus individual-level descriptions of health inequality reductions, 3)
      concrete versus abstract intervention scenarios, and 4) online versus face-to
      face mode of administration. Fifty-two members of the public participated in face
      to-face discussion groups, while 83 members of the public completed an online
      survey. Participants were given a questionnaire instrument with different
      scenario descriptions for eliciting aversion to social inequality in health.
      RESULTS: The median respondent was inequality averse under all scenarios.
      Scenarios involving small rather than unrealistically large health gains made
      little difference in terms of inequality aversion, as did population-level rather
      than individual-level scenarios. However, the proportion expressing extreme
      inequality aversion fell 19 percentage points when considering a specific health
      intervention scenario rather than an abstract scenario and was 11 to 21
      percentage points lower among online public respondents compared with the
      discussion group. CONCLUSIONS: Our study suggests that both concrete scenarios
      and online administration reduce the proportion expressing extreme inequality
      aversion but still yield median responses that imply substantial health
      inequality aversion.

PMID- 28441099
TI  - The Comprehensive Female Soldier Support Model.
AB  - Women represent a small minority in the U.S. military and an even smaller
      minority in the military chaplaincy. Prior to this study, the U.S. Army
      chaplaincy did not have a gender-specific model for providing support to women
      soldiers. In this Delphi research project, wounded women soldiers and female
      military chaplains provided expert opinions to develop the comprehensive female
      soldier support model (CFS2). Ten military women and 11 female chaplains who had
      been deployed overseas contributed to the body of knowledge related to the
      understanding of the emotional and spiritual support needs of wounded female
      soldiers. Five key findings appeared in the study: (a) many women did not get the
      chaplain support they needed; (b) the gender of the chaplain was not significant;

PMID- 28441100
TI  - Women's health as an ideological and political issue: Restricting the right to
      abortion, access to in vitro fertilization procedures, and prenatal testing in
      Poland.
AB  - The authors describe the problems of women in Poland, who have limited access to
      abortion, in vitro fertilization procedures, and prenatal tests. The current
      situation stems from ideological pressure, which affects women's health issues.
      This is part of a broader syndrome of the conservative approach to women's health
      in Eastern Europe, as well as the factor that strengthens the extreme right in
      Europe. As women's sexual health is demonized, women less often undergo
      preventive examinations. Making the debate about health more rational requires
      radical sociocultural changes in this part of the world.

PMID- 28441101
TI  - Male-Centric and Female-Centric Pornography Consumption: Relationship With Sex
      Life and Attitudes in Young Adults.
AB  - Pornography availability has increased in recent years, and while there is plenty
      of speculation about its effects, empirical investigation about how porn
      influences our lives has yielded mixed results. Additionally, few studies have
      addressed the effects of specific pornography characteristics. Past research has
      shown that male-centric pornography can be related to negative outcomes, while
      female-centric pornography is related to more positive outcomes, particularly in
      women. The present survey study examined the relationship between pornography
      characteristics (male- and female-centric) and the self-reported attitudes and
      sexual experiences of men and women. Participants in the full sample were 195 men
      and 310 women who completed an online questionnaire. Although effect sizes were
      small, women who reported viewing pornography with more female-centric features
      also reported more positive effects of pornography on sex life and perceptions of
      the other gender. While men were more likely than women to report negative
      effects relating to pornography use on these same measures, there were very few
      reported negative effects of pornography overall. These findings demonstrate a
      small association between the use of female-centric pornography and more positive
      outcomes, particularly for women.

PMID- 28441102
TI  - The Importance of Intergenerational Communication in Advance Care Planning:
      Generational Relationships among Perceptions and Beliefs.
AB  - This study explores triadic intergenerational perceptions of family members'
      beliefs and behaviors that often impact an individual's willingness to engage in
      advance care planning. Using data from 189 triads of young adults, their parents,
      and their grandparents, we examined generational relationships among individuals'
      openness about death, death anxiety, knowledge of surrogate decision-making, and
      advance care planning self-efficacy. Results of this study found significant
      relationships between grandparents and parents, as well as between parents and
      children for all variables except self-efficacy. Additionally, results of this
      study found indirect relationships between grandparents and their grandchildren
      for three variables. These findings underscore the need to treat advance care
      planning as a family communication issue. Implications for how advance care
      planning should be approached in conversations with healthcare providers and
      within the family are discussed.

PMID- 28441103
TI  - Perceptions of Abusive Parenting Behaviors: A Preliminary Exploration Into the
      Underrecognition of Mother-Daughter Sexual Abuse.
AB  - The current study examined the influence of the sex of the parent and the sex of
      the child on perceptions of sexually abusive behaviors. Vignettes illustrating
      different forms of sexual abuse were rated by 124 participants, with the
      different parent-child pairs (mother-daughter, mother-son, father-daughter,
      father-son) substituted into the vignettes being the only difference between
      groups. Two-way between subjects ANOVAs revealed that sexually abusive behaviors
      by mothers were perceived as less damaging to child victims (F (1, 120 = 7.56, p
      < .01) than the same sexually abusive behaviors committed by fathers. In
      addition, sexually abusive behaviors by mothers toward daughters were perceived
      as the least abusive (F (1, 120 = 16.30, p < .001) and the least criminal (F (1,
      120 = 4.44, p < .05) as compared to the other three groups. Results suggest that
      perceptions of sexual abuse may be influenced by perceptions of sex and gender.

PMID- 28441104
TI  - Gestalt Intervention Groups for Anxious Parents in Hong Kong: A Quasi
      Experimental Design.
AB  - This study examined the impact of gestalt intervention groups for anxious Chinese
      parents in Hong Kong. A non-randomized control group pre-test/post-test design
      was adopted. A total of 156 parents participated in the project. After 4 weeks of
      treatment, the intervention group participants had lower anxiety levels, less
      avoidance of inner experiences, and more kindness towards oneself and mindfulness
      when compared to control group participants. However, the dimension of self
      judgment remained unchanged. The adaptation of gestalt intervention to suit the
      Chinese culture was discussed.

PMID- 28441106
TI  - JWH-122 Consumption Adverse Effects: A Case of Hallucinogen Persisting Perception
      Disorder Five-Year Follow-Up.
AB  - Synthetic cannabinoid receptor agonists are a heterogeneous group of psychotropic
      drugs functionally related to Delta9-tetrahydrocannabinol. These substances,
      marketed as cannabis substitutes, have been associated with numerous cases of
      severe intoxication and death across the world. In our article, we describe a
      case of hallucinogen persisting perception disorder developing in a natural
      cannabis user after consumption of JWH-122, a naphthoylindole largely used since
      2010. Clinical symptomatology persisted for about four years and was alleviated
      through treatment with clonazepam. Considering that natural cannabis consumption
      can induce the development of a hallucinogen persisting perception disorder, it
      is not excluded that, in our patient, symptoms lasted a long time due to cannabis
      consumption. This article describes the clinical evolution from onset to
      resolution of all symptoms.

PMID- 28441105
TI  - Transcriptomic dissection of the horizontally acquired response regulator EsrB
      reveals its global regulatory roles in the physiological adaptation and
      activation of T3SS and the cognate effector repertoire in Edwardsiella piscicida
      during infection toward turbot.
AB  - Edwardsiella piscicida is the leading pathogen threatening worldwide aquaculture
      industries. The 2-component system (TCS) EsrA-EsrB is essential for the
      pathogenesis of this bacterium. However, little is known about the regulon and
      regulatory mechanism of EsrA-EsrB or about the factors that mediate the
      interaction of TCS with bacterial hosts. Here, our RNA-seq analysis indicated
      that EsrB strongly induces type III and type VI secretion systems (T3/T6SS)
      expression and that it modulates the expression of both physiology- and virulence
      associated genes in E. piscicida grown in DMEM. EsrB binds directly to a highly
      conserved 18-bp DNA motif to regulate the expression of T3SS and other genes.
      EsrB/DMEM-activated genes include 3 known and 6 novel T3SS-dependent effectors.
      All these effector genes are highly induced by EsrB during the late stage of in
      vivo infection in fish. Furthermore, although in vivo colonization by the
      bacterium relies on EsrB and T3/T6SS expression, it does not require the
      expression of individual effectors other than EseJ. The mutant lacking these 9
      effectors showed significant defects in in vivo colonization and virulence toward
      turbot, and, more importantly, a high level of protection against challenges by
      wild-type E. piscicida, suggesting that it may represent a promising live
      attenuated vaccine. Taken together, our data demonstrate that EsrB plays a global
      regulatory role in controlling physiologic responses and the expression of T3SS
      and its cognate effector genes. Our findings will facilitate further work on the
      mechanism of molecular pathogenesis of this bacterium during infection.

PMID- 28441107
TI  - Coping With Sexual Orientation-Related Minority Stress.
AB  - Little is known about how adolescents cope with minority stressors related to
      sexual orientation. This study examined 245 lesbian, gay, and bisexual (LGB)
      young adult's (ages 21-25) retrospective reports of coping in response to LGB
      minority stress during adolescence (ages 13-19) to test the reliability and
      validity of a measure of minority stress coping. Further, the study examined
      associations between LGB minority stress coping and young adult psychosocial
      adjustment and high school attainment. Validation and reliability was found for
      three minority stress coping strategies: LGB-specific strategies (e.g.,
      involvement with LGBT organizations), alternative-seeking strategies (e.g.,
      finding new friends), and cognitive strategies (e.g., imagining a better future).
      LGB-specific strategies were associated with better psychosocial adjustment and
      greater likelihood of high school attainment in young adulthood, whereas
      alternative-seeking and cognitive-based strategies were associated with poorer
      adjustment and less likelihood of high school attainment.

PMID- 28441109
TI  - Meningococcal serogroup B vaccine: Knowledge and acceptability among parents in
      Italy.
AB  - This study aimed to evaluate the knowledge and attitudes about Meningococcal
      meningitis B and the relative vaccine for children among a sample of parents in
      Italy. A cross-sectional investigation was conducted from October to December
      2015 among a sample of 910 parents in the geographic area of Naples and Salerno
      (Italy). In total, 543 of 910 parents returned a completed questionnaire for a
      response rate of 59.7%. Almost all parents had heard about meningitis (95.8%),
      79.8% of these knew the mode of transmission (through respiratory droplets) and
      62.5% knew the susceptible population (infants, children and adolescents).
      Moreover, a large percentage (86%) knew that the vaccine is a preventive measure.
      Parents who were married, those who had one child, those who did not have
      information about the MenB vaccine by physicians and those who needed additional
      information about the MenB vaccine were more likely to know the vaccine as a
      preventive measure of meningitis. Regarding attitudes toward the MenB vaccine,
      approximately two thirds of parents considered the vaccine useful (67.2%) and
      said that they would vaccinate their children (64.1%). Parents who had
      administered at least one recommended vaccination to their children, those who
      considered the vaccine useful, those with need for additional information about
      the vaccine and those who knew that the vaccine was a preventive measure of
      meningitis were more likely to have a positive attitude to vaccinating their
      children. Considering the results of our study, it looks appropriate that the
      knowledge of the population about meningitis and its related vaccinations is
      improved through correct health education and effective vaccine strategies that
      are implemented by policy makers.

PMID- 28441108
TI  - Novel clades of the HU/IHF superfamily point to unexpected roles in the
      eukaryotic centrosome, chromosome partitioning, and biologic conflicts.
AB  - The HU superfamily of proteins, with a unique DNA-binding mode, has been
      extensively studied as the primary chromosome-packaging protein of the bacterial
      superkingdom. Representatives also play a role in DNA-structuring during
      recombination events and in eukaryotic organellar genome maintenance. However,
      beyond these well-studied roles, little is understood of the functional
      diversification of this large superfamily. Using sensitive sequence and structure
      analysis methods we identify multiple novel clades of the HU superfamily. We
      present evidence that a novel eukaryotic clade prototyped by the human CCDC81
      protein acquired roles beyond DNA-binding, likely in protein-protein interaction
      in centrosome organization and as a potential cargo-binding protein in
      conjunction with Dynein-VII. We also show that these eukaryotic versions were
      acquired via an early lateral transfer from bacteroidetes, where we predict a
      role in chromosome partition. This likely happened before the last eukaryotic
      common ancestor, pointing to potential endosymbiont contributions beyond that of
      the mitochondrial progenitor. Further, we show that the dramatic lineage-specific
      expansion of this domain in the bacteroidetes lineage primarily is linked to a
      functional shift related to potential recognition and preemption of genome
      invasive entities such as mobile elements. Remarkably, the CCDC81 clade has
      undergone a similar massive lineage-specific expansion within the archosaurian
      lineage in birds, suggesting a possible use of the HU superfamily in a similar
      capacity in recognition of non-self molecules even in this case.

PMID- 28441110
TI  - Effects of the US Food and Drug Administration Boxed Warning of Erythropoietin
      Stimulating Agents on Utilization and Adverse Outcome.
AB  - Purpose In March 2007, a US Food and Drug Administration boxed warning was issued
      for erythropoietin-stimulating agents (ESAs) regarding serious adverse events,
      such as venous thromboembolism (VTE). We evaluated the US Food and Drug
      Administration's boxed warning of ESAs used to treat chemotherapy-induced anemia
      because evidence on the effectiveness of boxed warnings remains inconclusive.
      Patients and Methods Using 2004 to 2009 SEER-Medicare data, we exploited a
      natural experiment to examine the effects of ESA boxed warnings on utilization
      and risk of VTE. The intervention group included Medicare fee-for-services
      patients diagnosed with colorectal, breast, or lung cancers targeted by this
      warning and undergoing chemotherapy; the control group included patients with
      myelodysplastic syndromes not targeted by this warning. The period from January
      2004 to September 2006 was used as the prewarning period; the period from April
      2007 to September 2009 was used as the postwarning period. The two binary
      dependent variables included ESA use and hospitalized VTE. Linear probability
      models with a difference-in-differences specification were used for estimation.
      Results Our sample consisted of 45,319 unique patients between 2004 and 2009. The
      trends in ESA use remained similar between the intervention and control groups
      before the warning, but started declining sharply in the intervention group only
      after the warning. The trends in hospitalized VTE were relatively stable.
      Regressions showed that the ESA boxed warning was associated with a 20.2
      percentage-point reduction ( P < .001) in the likelihood of ESAs being used to
      treat cancers targeted by the warning, but not significantly associated with the
      likelihood of hospitalized VTE. Conclusion Our study showed that the warning was
      effective in reducing ESA utilization. Future studies should examine other
      regulatory drug safety actions, such as the Risk Evaluation and Mitigation
      Strategy initiative, whose effectiveness remains unknown.

PMID- 28441112
TI  - Second-Line Hormonal Therapy for Men With Chemotherapy-Naive, Castration
      Resistant Prostate Cancer: American Society of Clinical Oncology Provisional
      Clinical Opinion.
AB  - Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO
      membership after publication or presentation of potential practice-changing data.
      This PCO addresses second-line hormonal therapy for chemotherapy-naive men with
      castration-resistant prostate cancer (CRPC) who range from being asymptomatic
      with only biochemical evidence of CRPC to having documented metastases but
      minimal symptoms. Clinical Context The treatment goal for CRPC is palliation.
      Despite resistance to initial androgen deprivation therapy, most men respond to
      second-line hormonal therapies. However, guidelines have neither addressed second
      line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with
      regard to the chemotherapy-naive population. Recent Data Six phase III randomized
      controlled trials and expert consensus opinion inform this PCO. Provisional
      Clinical Opinion For men with CRPC, a castrate state should be maintained
      indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors)
      may be considered in patients with nonmetastatic CRPC at high risk for metastatic
      disease (rapid prostate-specific antigen doubling time or velocity) but otherwise
      is not suggested. In patients with radiographic evidence of metastases and
      minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered
      after discussion with patients about potential harms, benefits, costs, and
      patient preferences. Radium-223 and sipuleucel-T also are options. No evidence
      provides guidance about the optimal order of hormonal therapies for CRPC beyond
      second-line treatment. Prostate-specific antigen testing every 4 to 6 months is
      reasonable for men without metastases. Routine radiographic restaging generally
      is not suggested but can be considered for patients at risk for metastases or who
      exhibit symptoms or other evidence of progression. Additional information is
      available at www.asco.org/genitourinary-cancer-guidelines and
      www.asco.org/guidelineswiki .

PMID- 28441111
TI  - Phase II Study of the Efficacy and Safety of Pembrolizumab for
      Relapsed/Refractory Classic Hodgkin Lymphoma.
AB  - Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1,
      leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2.
      Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high
      overall response rate (ORR) in patients with relapsed or refractory classic
      Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 (
      ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of
      pembrolizumab in three cohorts of patients with rrHL, defined on the basis of
      lymphoma progression after (1) autologous stem cell transplantation (ASCT) and
      subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus,
      ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without
      BV after transplantation. Patients received pembrolizumab 200 mg once every 3
      weeks. Response was assessed every 12 weeks. The primary end points were ORR by
      central review and safety. Results A total of 210 patients were enrolled and
      treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of
      analysis, patients received a median of 13 treatment cycles. Per central review,
      the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was
      22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2%
      for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response >= 6
      months. The safety profile was largely consistent with previous pembrolizumab
      studies. Conclusion Pembrolizumab was associated with high response rates and an
      acceptable safety profile in patients with rrHL, offering a new treatment
      paradigm for this disease.

PMID- 28441113
TI  - Research with American Indian and Alaska Native populations: Measurement matters.
AB  - Research is an important tool in addressing myriad American Indian and Alaska
      Native (AIAN) health disparities; however, tensions exist between common
      empirical measurement approaches that facilitate cross-cultural comparisons and
      measurement specificity that may be more valid locally and/or culturally
      appropriate. The tremendous diversity of AIAN communities, small population sizes
      of distinct AIAN cultural groups, and varying cultural contexts and worldviews
      should influence measurement decisions in health research. We provide a framework
      for guiding measurement in collaboration with AIAN communities using examples
      from substance abuse research for illustration. Our goal is to build upon ongoing
      efforts to advance measurement validity for AIAN research by engaging community
      researcher partnerships and critical thinking in the selection, adaptation,
      creation, and implementation of measures.

PMID- 28441114
TI  - Neural Circuitry of Reward Prediction Error.
AB  - Dopamine neurons facilitate learning by calculating reward prediction error, or
      the difference between expected and actual reward. Despite two decades of
      research, it remains unclear how dopamine neurons make this calculation. Here we
      review studies that tackle this problem from a diverse set of approaches, from
      anatomy to electrophysiology to computational modeling and behavior. Several
      patterns emerge from this synthesis: that dopamine neurons themselves calculate
      reward prediction error, rather than inherit it passively from upstream regions;
      that they combine multiple separate and redundant inputs, which are themselves
      interconnected in a dense recurrent network; and that despite the complexity of
      inputs, the output from dopamine neurons is remarkably homogeneous and robust.
      The more we study this simple arithmetic computation, the knottier it appears to
      be, suggesting a daunting (but stimulating) path ahead for neuroscience more
      generally.

PMID- 28441115
TI  - Neuromodulation of Innate Behaviors in Drosophila.
AB  - Animals are born with a rich repertoire of robust behaviors that are critical for
      their survival. However, innate behaviors are also highly adaptable to an
      animal's internal state and external environment. Neuromodulators, including
      biogenic amines, neuropeptides, and hormones, are released to signal changes in
      animals' circumstances and serve to reconfigure neural circuits. This circuit
      flexibility allows animals to modify their behavioral responses according to
      environmental cues, metabolic demands, and physiological states. Aided by
      powerful genetic tools, researchers have made remarkable progress in Drosophila
      melanogaster to address how a myriad of contextual information influences the
      input-output relationship of hardwired circuits that support a complex behavioral
      repertoire. Here we highlight recent advances in understanding neuromodulation of
      Drosophila innate behaviors, with a special focus on feeding, courtship,
      aggression, and postmating behaviors.

PMID- 28441116
TI  - Nerve Growth Factor and Pain Mechanisms.
AB  - Nerve growth factor (NGF) antagonism is on the verge of becoming a powerful
      analgesic treatment for numerous conditions, including osteoarthritis and lower
      back pain. This review summarizes the historical research, both fundamental and
      clinical, that led to our current understanding of NGF biology. We also discuss
      the surprising number of questions that remain about NGF expression patterns and
      NGF's various functions and interaction partners in relation to persistent pain
      and the potential side effects of anti-NGF therapy.

PMID- 28441117
TI  - Sexual Dimorphism of Parental Care: From Genes to Behavior.
AB  - Parental care is found in species across the animal kingdom, from small insects
      to large mammals, with a conserved purpose of increasing offspring survival. Yet
      enormous variability exists between different species and between the sexes in
      the pattern and level of parental investment. Here, we review the literature on
      the neurobiological mechanisms underlying maternal and paternal care, especially
      in rodents, and discuss the relationship between sex differences in behavior and
      sexual dimorphism in the brain. We argue that although several brain regions and
      circuits regulating parental care are shared by both sexes, some of the
      fundamental components comprising the maternal brain are innate and sex specific.
      Moreover, we suggest that a more comprehensive understanding of the underlying
      mechanisms can be achieved by expanding the methodological toolbox, applying
      ethologically relevant approaches such as nontraditional wild-derived animal
      models and complex seminatural experimental set-ups.

PMID- 28441118
TI  - Mechanisms of Hippocampal Aging and the Potential for Rejuvenation.
AB  - The past two decades have seen remarkable progress in our understanding of the
      multifactorial drivers of hippocampal aging and cognitive decline. Recent
      findings have also raised the possibility of functional rejuvenation in the aged
      hippocampus. In this review, we aim to synthesize the mechanisms that drive
      hippocampal aging and evaluate critically the potential for rejuvenation. We
      discuss the functional changes in synaptic plasticity and regenerative potential
      of the aged hippocampus, followed by mechanisms of microglia aging, and assess
      the cross talk between these proaging processes. We then examine proyouth
      interventions that demonstrate significant promise in reversing age-related
      impairments in the hippocampus and, finally, attempt to look ahead toward novel
      therapeutics for brain aging.

PMID- 28441119
TI  - Comparable efficacy of behavioral and pharmacological treatments among African
      American and White cocaine users.
AB  - Multiple randomized clinical trials (RCTs) have evaluated a range of treatments
      for cocaine dependence, but few of these have focused specifically on the racial
      diversity observed among cocaine-dependent patients. The present analyses
      evaluated racial variation in cocaine use and addiction-related psychosocial
      outcomes at baseline and follow-up among 388 African American and White adults
      participating in 1 of 5 RCTs evaluating a range of pharmacological and behavioral
      treatments for cocaine use disorders. General linear modeling (GLM) indicated
      significant racial variation in cocaine and psychosocial indicators at baseline.
      At baseline, there were significant racial differences in the number of days paid
      for work in the 30 days prior to the study, age, days of cocaine use in the past
      month, age of first cocaine use, psychosocial problems (i.e., employment,
      cocaine, legal, and family), public assistance status, and prevalence of lifetime
      anxiety disorders. There were no significant main or interaction effects of race
      and study on treatment outcomes at posttreatment. These findings suggest that
      despite significant racial differences at baseline, the pharmacological and
      behavioral treatments resulted in fairly comparable outcomes across racial groups
      in these 5 RCTs.

PMID- 28441120
TI  - Prevalence of Trachoma in Northern Benin: Results from 11 Population-Based
      Prevalence Surveys Covering 26 Districts.
AB  - AIMS: We sought to evaluate trachoma prevalence in all suspected-endemic areas of
      Benin. METHODS: We conducted population-based surveys covering 26 districts
      grouped into 11 evaluation units (EUs), using a two-stage, systematic and random,
      cluster sampling design powered at EU level. In each EU, 23 villages were
      systematically selected with population proportional to size; 30 households were
      selected from each village using compact segment sampling. In selected
      households, we examined all consenting residents aged one year or above for
      trichiasis, trachomatous inflammation - follicular (TF), and trachomatous
      inflammation - intense. We calculated the EU-level backlog of trichiasis and
      delineated the ophthalmic workforce in each EU using local interviews and
      telephone surveys. RESULTS: At EU-level, the TF prevalence in 1-9-year-olds
      ranged from 1.9 to 24.0%, with four EUs (incorporating eight districts)
      demonstrating prevalences >=5%. The prevalence of trichiasis in adults aged 15+
      years ranged from 0.1 to 1.9%. In nine EUs (incorporating 19 districts), the
      trichiasis prevalence in adults was >=0.2%. An estimated 11,457 people have
      trichiasis in an area served by eight ophthalmic clinical officers. CONCLUSION:
      In northern Benin, over 8000 people need surgery or other interventions for
      trichiasis to reach the trichiasis elimination threshold prevalence in each EU,
      and just over one million people need a combination of antibiotics, facial
      cleanliness and environmental improvement for the purposes of trachoma's
      elimination as a public health problem. The current distribution of ophthalmic
      clinical officers does not match surgical needs.

PMID- 28441121
TI  - An exploratory evaluation of the feasibility, acceptability, and efficacy of the
      mental fitness disordered eating program in schools.
AB  - The present study examines the feasibility, acceptability, and efficacy of a
      tiered professional development disordered eating prevention program. A
      pretest/posttest quasi-experimental design assessed elementary and junior high
      school faculty and staff's disordered eating knowledge and attitudes. Findings
      indicate participants experienced increased awareness of students' susceptibility
      to and the severity of disordered eating, increased self-efficacy about referring
      students to appropriate resources, and overall perceived acceptability of the
      training. Improved knowledge and attitudes suggest faculty and staff are better
      equipped to identify at-risk individuals at an early stage, increasing the
      likelihood of recovery from disordered eating behaviors or disordered eating.

PMID- 28441122
TI  - 2017 Canadian Society of Surgical Oncology Annual Scientific Meeting Abstracts

PMID- 28441123
TI  - Recruitment: a perennial question.

PMID- 28441127
TI  - Physician recruitment and retention in Manitoba: results from a survey of
      physicians' preferences for rural jobs.
AB  - INTRODUCTION: Rural recruitment and retention continues to present challenges to
      health workforce planners. This paper reports and analyzes the results of a
      survey sent to physicians in Manitoba, eliciting their opinions regarding rural
      jobs. METHODS: A survey was sent to all physicians in Manitoba. Part 1 of the
      survey included questions about background and demographic information; part 2
      was a set of job satisfaction questions regarding respondents' current job; and
      part 3 included 2 sets of stated-choice questions eliciting preferences for a set
      of attributes relevant to rural recruitment and retention. RESULTS: Of the 2487
      physicians who received surveys, 561 (22.6%) responded. Respondents indicated
      that income, hours worked and on-call frequency are very important: overall job
      satisfaction increased with income and decreased with hours worked. Income, hours
      and on-call frequency were ranked "very important" by the largest proportions of
      physicians. The estimated compensation for on-call more frequent than 1-in-4 was
      very high (82% of average income), and additional hours worked were worth $183
      per hour. Other attributes that were important included professional interaction,
      housing availability and community incentives during the first year, which were
      valued at 11%-31% of annual income. CONCLUSION: Work-life balance is a key
      consideration for rural jobs, and there are incentives that can compensate for
      less desirable attributes.

PMID- 28441128
TI  - Early-career work location of Memorial University medical graduates: Why the
      decline in rural practice?
AB  - INTRODUCTION: In a previous study, we found a decline in the proportion of
      Memorial University of Newfoundland (MUN) medical alumni practising in rural
      areas, particularly in Newfoundland and Labrador. The current study focused on
      the work location of recent graduates and examined the predictors of working in
      rural Canada and in rural Newfoundland and Labrador within the first 15 years
      following graduation. METHODS: We linked data from graduating class lists and the
      alumni and postgraduate databases with Scott's Medical Database to create a
      record of all graduates from 1973 to 2008, including their work location. We
      identified differences and significant predictors for each outcome and then
      described and compared the characteristics of 4 cohorts of graduating classes.
      RESULTS: In their early career, 127/1113 (11.4%) MUN medical graduates were
      working in rural Canada, and 57 (5.1%) were working in rural Newfoundland and
      Labrador. Having a rural background and being a family physician were predictors
      of working in rural Canada, and having a rural background, doing at least part of
      the residency at MUN, being from Newfoundland and Labrador and being a family
      physician were predictors of working in rural Newfoundland and Labrador. Seventy
      four (13.6%) and 33 (6.1%) of 1989-1998 graduates worked in rural Canada and
      rural Newfoundland and Labrador, respectively, compared to 53 (9.3%) and 24
      (4.2%), respectively, of 1999-2008 graduates. CONCLUSION: The proportion of MUN
      medical graduates who worked in rural communities early in their career decreased
      among recent cohorts. The results show the impact of changes in the
      characteristics of MUN medical graduates, who increasingly opt for specialist
      practice and residency training outside the province, and the important role of
      local postgraduate training.

PMID- 28441130
TI  - Country cardiograms case 59.

PMID- 28441129
TI  - Medical school outreach and mentorship for rural secondary school students: a
      pilot of the Southwestern Ontario Medical Mentorship Program.
AB  - INTRODUCTION: Rural communities in Canada face challenges with physician
      recruitment. Physicians from rural backgrounds are more likely to practise in
      rural areas; however, rural students are underrepresented in medical schools. To
      address this, the Southwestern Ontario Medical Mentorship Program (SWOMMP) was
      created to expose rural secondary school students to medical careers. METHODS:
      This pilot project involved a school-based interactive session run by rural
      medical students on paths to medicine, medical specialties and skills workshops
      of roughly 2.5 hours targeted to grades 10-12 university-level students in rural
      southwestern Ontario. Two sessions were held, 1 in a town with a population of 20
      000 and the other in a town with a population of 5000. A survey was administered
      before and after the session to assess changes in interest in medical careers and
      in perceived barriers. RESULTS: Forty-five students participated in the sessions.
      After the sessions, 32 students (71%) were considering a career in health care,
      compared to 26 (58%) before the sessions. Almost all students (43 [96%]) found
      the session helpful or extremely helpful, and all reported they would recommend
      it to other classes. Finances, grades and length of schooling were the most
      commonly perceived barriers to pursuing a career in medicine; fewer students had
      concerns about finances and length of schooling after the sessions. Twenty-nine
      students (64%) enrolled in longitudinal mentorship with a medical student.
      CONCLUSION: This pilot project showed that a rural secondary school outreach
      program run by medical students can increase high school students' interest in
      medical careers. The project will continue and aims to expand and improve using
      the pilot study's data.

PMID- 28441131
TI  - The occasional treatment of opioid use disorder.

PMID- 28441132
TI  - Country cardiograms case 59: Answer.

PMID- 28441134
TI  - Spiders on the move.

PMID- 28441133
TI  - Transport of critically ill patients.

PMID- 28441136
TI  - Electronic cigarettes: the lesser of two evils, but how much less?

PMID- 28441138
TI  - Employing RNA viruses to fight cancer: novel insights into oncolytic virotherapy.
AB  - Within recent decades, viruses that specifically target tumor cells have emerged
      as novel therapeutic agents against cancer. These viruses do not only act via
      their cell-lytic properties, but also harbor immunostimulatory features to re
      direct the tumor microenvironment and stimulate tumor-directed immune responses.
      Furthermore, oncolytic viruses are considered to be superior to classical cancer
      therapies due to higher selectivity towards tumor cell destruction and,
      consequently, less collateral damage of non-transformed healthy tissue. In
      particular, the field of oncolytic RNA viruses is rapidly developing since these
      agents possess alternative tumor-targeting strategies compared to established
      oncolytic DNA viruses. Thus, oncolytic RNA viruses have broadened the field of
      virotherapy facilitating new strategies to fight cancer. In addition to several
      naturally occurring oncolytic viruses, genetically modified RNA viruses that are
      armed to express foreign factors such as immunostimulatory molecules have been
      successfully tested in early clinical trials showing promising efficacy. This
      review aims to provide an overview of the most promising RNA viruses in clinical
      development, to summarize the current knowledge of clinical trials using these
      viral agents, and to discuss the main issues as well as future perspectives of
      clinical approaches using oncolytic RNA viruses.

PMID- 28441139
TI  - Empirical Likelihood in Nonignorable Covariate-Missing Data Problems.
AB  - Missing covariate data occurs often in regression analysis, which frequently
      arises in the health and social sciences as well as in survey sampling. We study
      methods for the analysis of a nonignorable covariate-missing data problem in an
      assumed conditional mean function when some covariates are completely observed
      but other covariates are missing for some subjects. We adopt the semiparametric
      perspective of Bartlett et al. (Improving upon the efficiency of complete case
      analysis when covariates are MNAR. Biostatistics 2014;15:719-30) on regression
      analyses with nonignorable missing covariates, in which they have introduced the
      use of two working models, the working probability model of missingness and the
      working conditional score model. In this paper, we study an empirical likelihood
      approach to nonignorable covariate-missing data problems with the objective of
      effectively utilizing the two working models in the analysis of covariate-missing
      data. We propose a unified approach to constructing a system of unbiased
      estimating equations, where there are more equations than unknown parameters of
      interest. One useful feature of these unbiased estimating equations is that they
      naturally incorporate the incomplete data into the data analysis, making it
      possible to seek efficient estimation of the parameter of interest even when the
      working regression function is not specified to be the optimal regression
      function. We apply the general methodology of empirical likelihood to optimally
      combine these unbiased estimating equations. We propose three maximum empirical
      likelihood estimators of the underlying regression parameters and compare their
      efficiencies with other existing competitors. We present a simulation study to
      compare the finite-sample performance of various methods with respect to bias,
      efficiency, and robustness to model misspecification. The proposed empirical
      likelihood method is also illustrated by an analysis of a data set from the US
      National Health and Nutrition Examination Survey (NHANES).

PMID- 28441140
TI  - Teaching trainees how to critically evaluate the literature - a crossover study
      at two pediatric residency programs.
AB  - Objectives: The purpose of this study was to assess the efficacy of a concise,
      evidence based medicine curriculum in improving the knowledge of pediatric
      residents at two institutions. Methods: Sixty first and second year pediatric
      residents at MassGeneral Hospital for Children and MedStar Georgetown University
      Hospital participated in a crossover study. The evidence based medicine
      curriculum, consisting of 4 ninety minute sessions grounded in adult learning
      theory principles, was developed using the methodology described in the book
      'Studying a Study'. A validated 20 question evidence based medicine multiple
      choice test was administered on three separate occasions to measure baseline
      knowledge, efficacy of the curriculum in improving knowledge, and long term
      retention of that knowledge. Results: Post curriculum, the fall group's scores
      improved 23% from baseline (M=10.3, SD=2.4) to (M=12.7, SD=3.0) students (t(26)=
      3.29, p=0.0018) while the spring group improved by 41% (M=10.0, SD=2.8) to
      (M=14.1, SD=2.2) students (t(32)=-6.46, p<0.0001).  When re-tested 4-6 months
      later, the fall group's scores did not significantly decline from their immediate
      post curriculum scores (M=12.7, SD=3.0) to (M=11.7, SD=3.0) students (t(32)
      =1.33, p=0.190). There was an association between number of sessions attended and
      increase in post curriculum score (chi2(3, N=60) =11.75, p=0.0083). Conclusions:
      Findings demonstrate our curriculum was effective in teaching evidence based
      medicine to pediatric residents, and fostered long term retention of knowledge. 
      Based on these results, we believe this curriculum could be implemented at any
      institution.

PMID- 28441141
TI  - Crystal growth and stoichiometry-dependent properties of the ferromagnetic Weyl
      semimetal ZrCo2-x Sn.
AB  - We report the growth of high quality bulk crystals, through crystallization from
      molten Sn flux, of the predicted ferromagnetic Weyl metal ZrCo2-x Sn with the L21
      Heusler phase structure. The concentration of Co vacancies in the single crystals
      is found to be dependent on the initial concentration of Co in the flux. The
      saturation magnetization increases approximately linearly with decreasing Co
      deficiency and the ferromagnetic transition temperature changes significantly. p
      type carrier conduction and an anomalous Hall effect are observed. The calculated
      electronic density of states of ZrCo2-x Sn shows a significant change in minority
      and majority spin state occupancies and a shift in the Fermi level with Co
      deficiency.

PMID- 28441135
TI  - Proteomic mapping of cytosol-facing outer mitochondrial and ER membranes in
      living human cells by proximity biotinylation.
AB  - The cytosol-facing membranes of cellular organelles contain proteins that enable
      signal transduction, regulation of morphology and trafficking, protein import and
      export, and other specialized processes. Discovery of these proteins by
      traditional biochemical fractionation can be plagued with contaminants and loss
      of key components. Using peroxidase-mediated proximity biotinylation, we captured
      and identified endogenous proteins on the outer mitochondrial membrane (OMM) and
      endoplasmic reticulum membrane (ERM) of living human fibroblasts. The proteomes
      of 137 and 634 proteins, respectively, are highly specific and highlight 94
      potentially novel mitochondrial or ER proteins. Dataset intersection identified
      protein candidates potentially localized to mitochondria-ER contact sites. We
      found that one candidate, the tail-anchored, PDZ-domain-containing OMM protein
      SYNJ2BP, dramatically increases mitochondrial contacts with rough ER when
      overexpressed. Immunoprecipitation-mass spectrometry identified ribosome-binding
      protein 1 (RRBP1) as SYNJ2BP's ERM binding partner. Our results highlight the
      power of proximity biotinylation to yield insights into the molecular composition
      and function of intracellular membranes.

PMID- 28441142
TI  - Magnetization dynamics in magnonic structures with different geometries:
      interfaces, notches and waveguides.
AB  - The discovery of ultrafast magnetization dynamics 20 years ago has led to a broad
      variety of experimental techniques to explore phenomena in magnetic materials
      with high temporal resolution. In the current article we present a study dealing
      with broadband excitation of spin-wave packets at different magnonic crystal
      continuous magnetic film interfaces. Similar to protected conducting states on
      the surfaces of topological band insulators, these interfaces exhibit surface
      spin-wave modes that propagate out of the crystal into the continuous film. The
      propagation distance depends on the direction of the applied magnetic field as
      well as the surface geometry of the crystal.

PMID- 28441143
TI  - Ultrafast demagnetization in bulk versus thin films: an ab initio study.
AB  - We report ab initio simulations of the quantum dynamics of electronic charge and
      spins when subjected to intense laser pulses. By performing these purely electron
      dynamics calculations for a thin film and for the bulk of Ni, we conclude that
      formation of surfaces has a dramatic influence of amplifying the laser induced
      demagnetization. The reason for this amplification is enhanced spin-currents on
      the surface of the thin films. We show that the underlying physics of
      demagnetization for bulk is dominated by spin-flips induced by spin-orbit
      coupling. In the case of thin films, the dominant cause of demagnetization is a
      combination of the flow of spin-currents and spin-flips. Furthermore, a
      comparison of our results with experimental data shows that below  ~120 fs
      processes of demagnetization are entirely dominated by purely electronic
      processes followed by which dissipative effects like the Elliott-Yafet mechanism
      start to contribute significantly.

PMID- 28441144
TI  - Highly efficient inverted organic light emitting diodes by inserting a zinc
      oxide/polyethyleneimine (ZnO:PEI) nano-composite interfacial layer.
AB  - The electrode/organic interface is one of the key factors in attaining superior
      device performance in organic electronics, and inserting a tailor-made layer can
      dramatically modify its properties. The use of nano-composite (NC) materials
      leads to many advantages by combining materials with the objective of obtaining a
      desirable combination of properties. In this context, zinc
      oxide/polyethyleneimine (ZnO:PEI) NC film was incorporated as an interfacial
      layer into inverted bottom-emission organic light emitting diodes (IBOLEDs) and
      fully optimized. For orange-red emissive MEH-PPV based IBOLEDs, a high power
      efficiency of 6.1 lm W-1 at a luminance of 1000 cd m-2 has been achieved.
      Notably, the external quantum efficiency (EQE) increased from 0.1 to 4.8% and the
      current efficiency (CE) increased from 0.2 to 8.7 cd A-1 with rise in luminance
      (L) from 1000 to above 10 000 cd m-2 levels when compared to that of pristine ZnO
      based devices. An identical device architecture containing a ZnO:PEI NC layer has
      also been used to successfully fabricate green and blue emissive IBOLEDs. The
      significant enhancement in the inverted device performance, in terms of luminance
      and efficiency, is attributed to a good energy-level alignment between the
      cathode/organic interface which leads to effective carrier balance, resulting in
      efficient radiative-recombination.

PMID- 28441145
TI  - Laser-induced ultrafast spin current pulses: a thermodynamic approach.
AB  - The ultrafast demagnetization process allows for the generation of femtosecond
      spin current pulses. Here, we present a thermodynamic model of the spin current
      generation process, based on the chemical potential gradients as the driving
      force for the spin current. We demonstrate that the laser-induced spin current
      can be estimated by an easy to understand diffusion model.

PMID- 28441146
TI  - Epigenetic regulation of glucose metabolism.
AB  - PURPOSE OF REVIEW: Glucose metabolism is a central process in mammalian energy
      homeostasis. Its deregulation is a key factor in development of metabolic disease
      like diabetes and cancer. In recent decades, our understanding of gene regulation
      at the signaling, chromatin and posttranscriptional levels has seen dramatic
      developments. RECENT FINDINGS: A number of epigenetic mechanisms that do not
      affect the genetic code can be assessed with new technologies. However,
      increasing complexity becomes a major challenge for translation into clinical
      application. SUMMARY: The current review provides an update of transcriptional
      control of glucose metabolism, focusing on epigenetic regulators, DNA
      methylation, histone modifications and noncoding RNAs. Recent studies heavily
      support the importance of those mechanisms for future therapeutics and preventive
      efforts for metabolic diseases.

PMID- 28441147
TI  - Can the generic antiretroviral industry support access to a universal
      antiretroviral regimen?
AB  - PURPOSE OF REVIEW: The generic antiretroviral (ARV) industry played a critical
      role in the massive scale-up of HIV treatment in low-income and middle-income
      countries since 2000. As the global community looks ahead to a universal
      antiretroviral regimen, this article considers the industry's role in supporting
      universal access to affordable, simpler, more durable, and tolerable HIV
      treatment regimens. RECENT FINDINGS: Generic manufacturers made treatment scale
      up in low-income and middle-income countries possible through reducing prices,
      combining molecules from different originator companies to develop optimal fixed
      dose combinations, and investing in production capacity to meet escalating
      demand. Achieving scale-up of a universal regimen will require continued
      partnership in these areas. Collaboration on the demand and supply sides of the
      ARV marketplace will be required to foster a healthy and sustainable marketplace
      for new regimens. This includes clear priority setting from the global treatment
      community on priority products; predictable demand; regulatory prioritization of
      optimal products; effective tendering and procurement practices that enable
      multiple suppliers to participate in the market; coordinated product introduction
      efforts between Ministries of Health, partners, and civil society; and
      transparency from both buyers and suppliers to promote and monitor supply
      security. SUMMARY: New regimens will benefit people living with HIV, as well as
      buyers and generic suppliers, by maximizing existing production capacity and
      treatment budgets to reach the 90-90-90 goals.

PMID- 28441148
TI  - Health-Related Quality of Life and Cancer-Related Symptoms During
      Interdisciplinary Outpatient Rehabilitation for Malignant Brain Tumor.
AB  - OBJECTIVE: The aim of the study was to determine the relationships between
      functional outcomes, clinical symptoms, and health-related quality of life among
      patients with malignant brain tumors receiving interdisciplinary outpatient
      rehabilitation. DESIGN: A prospective study of 49 adults with malignant brain
      tumors participating in outpatient therapies was performed. Outcome measures
      included the Functional Assessment of Cancer Therapy-Brain (FACT-Br) for health
      related quality of life and the Patient-Reported Outcome Measures Instrument
      Survey (PROMIS) Depression and Pain Behavior scales measured at admission,
      discharge, 1 and 3 mos after discharge. Day Rehabilitation Outcome Scale
      (DayROS), a functional measure, was measured at admission and discharge. RESULTS:
      The FACT-Br scores, PROMIS pain, and PROMIS depression scores did not
      significantly change. There were many negative associations seen between FACT-Br
      and PROMIS depression (all P < .0001) and less associations with PROMIS pain.
      There was a positive correlation between Day Rehabilitation Outcome Scale and
      FACT-Br (P = .0058) and a negative association with PROMIS pain (P = .028), but
      not with PROMIS depression. There were no correlations between Day Rehabilitation
      Outcome Scale gains and change in PROMIS depression, FACT-Br total, or PROMIS
      pain. CONCLUSIONS: Health-related quality of life, pain, and depression did not
      worsen. Patients who reported less depression and pain had better reported health
      related quality of life. Level of function was also associated with HRQOL and
      pain, but not depression.

PMID- 28441150
TI  - Long non-coding RNAs in leukemia: biology and clinical impact.
AB  - PURPOSE OF REVIEW: Over the last years, long non-coding RNAs (lncRNAs) have
      emerged as putative regulators of malignant hematopoietic development. Here, we
      review recent literature on the involvement of lncRNAs in leukemia, including
      their role in driving or sustaining disease and their potential impact on
      diagnosis, classification, and prognosis. RECENT FINDINGS: Leukemogenesis is a
      complex process resulting from the accumulation of multiple genetic alterations.
      Over the last years, advances in high-throughput sequencing and transcriptome
      profiling have enabled the identification of lncRNAs involved in leukemia
      development. lncRNAs are able to distinguish different subtypes of human leukemia
      and several reports have identified specific patterns of lncRNA expression
      associated with clinical patient characteristics. Although functional studies on
      the actual role of these lncRNAs during transformation remain scarce, emerging
      evidence suggests that complex interactions between coding and non-coding
      transcript are truly involved in leukemia development. SUMMARY: Introduction of
      lncRNAs as an additional layer of complexity in human leukemia might provide new
      molecular genetic insights in the biology of this disease and could create unique
      opportunities for the identification of novel drug targets and diagnostic or
      prognostic biomarkers.

PMID- 28441151
TI  - Recent clinical trials in valvular heart disease.
AB  - PURPOSE OF REVIEW: With widespread adoption of transcatheter aortic valve
      replacement, there has been a change in the approach to management of valvular
      heart disease. New interest has taken hold in transcatheter therapies for
      valvular heart disease, as well as research into pathophysiology and progression
      of disease. Additionally, several key trials have further refined our
      understanding of surgical management of valvular heart disease. This review will
      elucidate recent clinical trial data leading to changes in practice. RECENT
      FINDINGS: There have been several landmark trials expanding the indications for
      transcatheter aortic valve replacement. Additionally, although still early,
      trials are beginning to demonstrate the feasibility and safety of transcatheter
      mitral valves. Options for transcatheter management of right-sided valvular
      disease continue to evolve, and these are areas of active investigation. SUMMARY:
      The emergence of novel therapies for valvular heart disease has expanded the
      management options available, allowing physicians to better individualize
      treatment of patients with valvular heart disease. This review will focus on the
      recent (within 2 years) trials in this field of interest.

PMID- 28441149
TI  - Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma.
AB  - PURPOSE OF REVIEW: Next generation sequencing and large-scale analysis of patient
      specimens has created a more complete picture of multiple myeloma (MM) revealing
      that epigenetic deregulation is a prominent factor in MM pathogenesis. RECENT
      FINDINGS: Over half of MM patients have mutations in genes encoding epigenetic
      modifier enzymes. The DNA methylation profile of MM is related to the stage of
      the disease and certain classes of mutations in epigenetic modifiers are more
      prevalent upon disease relapse, suggesting a role in disease progression. Many
      small molecules targeting regulators of epigenetic machinery have been developed
      and clinical trials are underway for some of these in MM. SUMMARY: Recent
      findings suggest that epigenetic targeting drugs could be an important strategy
      to cure MM. Combining these agents along with other strategies to affect the MM
      cell such as immunomodulatory drugs and proteasome inhibitors may enhance
      efficacy of combination regimens in MM.

PMID- 28441152
TI  - Cryoablation in the management of Barrett's esophagus.
AB  - PURPOSE OF REVIEW: Providing an overview on types of cryotherapy for esophageal
      application and their role in the management of Barrett's esophagus. RECENT
      FINDINGS: Recent studies have involved multiple types of cryotherapy including
      cryospray techniques that use either liquid nitrogen or carbon dioxide as the
      cryogenic fluid, and the CryoBalloon focal ablation device that uses nitrous
      oxide. Overall, studies report cryotherapy to be safe and effective in
      eradicating Barrett's epithelium. However, substantial variations among these
      studies in design and outcomes preclude direct comparisons of the results.
      Moreover, little is known of the long-term outcomes of cryotherapy, with only one
      report describing 5-year follow-up of patients treated with liquid nitrogen
      cryospray. SUMMARY: The concept of cryotherapy is appealing. By preserving the
      extracellular matrix and inducing anesthetic effects, cryotherapy has the
      potential to enable deeper ablations with less pain and a lower rate of stricture
      formation than radiofrequency ablation. To date, however, these potential
      benefits remain unproved. Prospective studies with clearly defined endpoints and
      longer follow-up are necessary to determine the role of cryotherapy in the
      management of patients with Barrett's esophagus.

PMID- 28441153
TI  - Discharge Criteria for the Late Preterm Infant: A Review of the Literature.
AB  - BACKGROUND: Standardized late preterm infant (LPI) discharge criteria ensure best
      practice and help guide the neonatal provider to determine the appropriate level
      of care following birth. However, the location can vary from the well newborn
      setting to the neonatal intensive care unit (NICU). PURPOSE: The purpose of this
      review is to examine differences in LPI discharge criteria between the well
      newborn setting and the NICU by answering the clinical questions, "What are the
      recommended discharge criteria for the LPI and do they differ if admitted to the
      well newborn setting versus the NICU?" SEARCH STRATEGY: Databases searched
      include CINAHL, TRIP, PubMed, and the Cochrane Library. Focusing first on the
      highest level of evidence, position statements, policy statements, and clinical
      practice guidelines were reviewed, followed by original research. RESULTS: There
      were few differences shown between settings. Discharge criteria included
      physiological stability and completed screenings for hearing loss,
      hyperbilirubinemia, car seat safety, hypoglycemia, critical congenital heart
      disease, and sepsis. Parent education is provided on umbilical cord care,
      feeding, elimination, and weight gain norms. Recommended maternal assessment
      included screenings for depression, drug use, safe home environment, and presence
      of social support. In general, research supported protecting the mother-infant
      dyad. IMPLICATIONS FOR PRACTICE AND RESEARCH: Developing a standardized approach
      for discharge criteria for LPIs may improve outcomes and reduce maternal stress.
      Research is needed to compare health and cost outcomes between settings.Video
      Abstract available at http://links.lww.com/ANC/A29.

PMID- 28441154
TI  - Clarifying complex inheritance: apolipoprotein C3 and atherosclerosis.
AB  - PURPOSE OF REVIEW: To describe some steps in the progress in the molecular
      biology of a peptide, apolipoprotein C3; its gene mutations that render
      individuals susceptible or resistant to developing hyperlipidaemia and
      atherosclerosis. RECENT FINDINGS: Data that lead to the development of a new
      therapeutic agent volanesorsen. SUMMARY: The agent blocks the function of the
      mRNA of apolipoprotein C3 and successfully treats severe hypertriglyceridaemia in
      phase 3 trials (Ionis Pharmaceuticals).

PMID- 28441155
TI  - Do triglyceride-lowering drugs decrease risk of cardiovascular disease?
AB  - PURPOSE OF REVIEW: This review summarizes the evidence supporting a relationship
      between lowering triglycerides (TGs) and TG-rich lipoprotein cholesterol (TGRL-C)
      levels and reduced atherosclerotic cardiovascular disease (ASCVD) event risk.
      RECENT FINDINGS: Data from observational investigations, including studies of
      genetic variants, provide evidence consistent with a causal relationship between
      elevations in TG and TGRL-C and greater risk for ASCVD. Randomized controlled
      trial evidence of ASCVD risk reduction with therapies that substantially lower TG
      and TGRL-C is limited by the fact that no large-scale trial results have been
      published from a study that enrolled subjects selected specifically on the basis
      of TG or TGRL-C elevation, although three such trials are underway or in the
      planning stages. Subgroup analyses from randomized controlled trials are
      suggestive of a reduction in coronary heart disease and ASCVD event rates with
      statins, fibrates, omega-3 fatty acid concentrates, and niacin in subjects with
      elevated TGs, particularly if accompanied by low high-density lipoprotein
      cholesterol. Mechanistic studies also support the biologic plausibility of this
      relationship. SUMMARY: In conclusion, the available data are suggestive of a
      benefit of ASCVD reduction with therapies that lower TG and TGRL-C; results from
      ongoing outcomes trials are expected to provide definitive evidence of this
      relationship.

PMID- 28441156
TI  - Interpreting lipoproteins in nonalcoholic fatty liver disease.
AB  - PURPOSE OF REVIEW: The pathophysiologies of nonalcoholic fatty liver disease
      (NAFLD), metabolic syndrome, and cardiovascular disease are closely interlinked
      and associated with atherogenic dyslipidemia. Liver and cardiovascular disease
      may silently progress to advanced stages if alarming signs, such as abdominal
      obesity, elevated fasting and postprandial triglycerides, and low HDL cholesterol
      are overlooked. We review the metabolic mechanisms in NAFLD at the cellular level
      in the context of standard clinical lipid measurements. RECENT FINDINGS: We
      discuss the pathogenesis of NAFLD, nonalcoholic steatohepatitis (NASH), and
      metabolic syndrome, atherogenic dyslipidemia, lipotoxicity, and lipophagy.
      SUMMARY: Physicians should infer from biomarkers or clinical findings that their
      abdominally obese patients are at risk of severe cardiovascular, liver fatty
      disease, or both. Physicians should carry out laboratory tests of plasma
      cholesterol, triglycerides, LDL and HDL cholesterol, non-HDL cholesterol,
      apolipoprotein B and platelets, and for diabetes, but importantly, plasma
      triglycerides also in the nonfasting state. But note, clinical routine plasma
      lipid and lipoprotein measurements are not necessarily reliable for interpreting
      severe metabolic changes. Notably, in advanced stages of NAFLD (i.e., late
      steatohepatitis and cirrhosis), routine lipid profiles do not necessarily show
      any more abnormalities.

PMID- 28441157
TI  - New role of mechanical assist device as bridge to transplant: USA perspective.
AB  - PURPOSE OF REVIEW: Cardiac transplant remains the gold standard of care for
      patients with end-stage heart failure. Unfortunately, due to the limited
      availability of donor hearts in the United States, not all eligible candidates
      are able to be transplanted. Since the introduction of mechanical assist devices
      for the treatment of advanced heart failure, patients gain a significant survival
      benefit while awaiting transplant. With rapidly evolving technology, it is
      important to appreciate the advances in the current use of mechanical assist
      devices. RECENT FINDINGS: Following a comprehensive analysis of novel therapies
      in end-stage heart failure, there is an enhancement in quality of life and life
      expectancy following implantation of left ventricular (LV) assist devices
      (LVADs). When implanted in suitable patients as bridge-to-transplant or
      'destination therapy', recipients demonstrate superior outcomes and survival
      compared with those who remain on optimal medical therapy. SUMMARY: The use of LV
      assist devices (LVADs) as bridge to transplantation has gained popularity over
      the last decade. It is recognized as an integral treatment modality in end-stage
      heart failure to those awaiting heart transplantation. When implanted in the
      appropriately chosen patient, it is superior to medical treatment alone and has
      shown noninferiority to heart transplantation while allowing for optimal
      functional status and preservation of end organ function.

PMID- 28441158
TI  - Message From the MIRC President.

PMID- 28441159
TI  - Application of High-Speed T1 Sequences for High-Quality Hepatic Arterial Phase
      Magnetic Resonance Imaging: Intraindividual Comparison of Single and Multiple
      Arterial Phases.
AB  - PURPOSE: The aim of this study was to compare intraindividual single and multiple
      arterial phase acquisitions and evaluate which acquisition method was more
      advantageous for obtaining high-quality hepatic arterial phase in gadoxetic acid
      enhanced liver magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixty
      seven patients who underwent gadoxetic acid-enhanced liver MRIs and had all 3
      kinds of acquisitions (single, dual, and triple arterial phases) were
      retrospectively included. For hepatic arterial phase imaging, controlled aliasing
      in parallel imaging results in higher acceleration (CAIPIRINHA) with or without
      time-resolved imaging with interleaved stochastic trajectories (TWIST) was used.
      The adequacy of optimal hepatic arterial timing was assessed and respiratory
      motion artifacts were rated using a 5-point scale, with the highest score
      indicating the worst image quality. Optimal timing and respiratory motion
      artifacts among 3 different acquisitions were compared using Fisher exact test
      and repeated measures one-way analysis of variance with multiple comparisons.
      RESULTS: Optimal timing of hepatic arterial phase was observed in 89.6% (60/67)
      of single arterial phase acquisitions and 98.5% (66/67) of both dual and triple
      arterial phase acquisitions (P = 0.015). Respiratory motion artifact was
      significantly lower in single and dual arterial acquisitions than in triple
      arterial acquisition (mean score, 1.70 vs 1.90 vs 2.49; P < 0.001), although
      there was no significant difference between single and dual arterial acquisitions
      (P = 0.091). CONCLUSIONS: A 15-second breath-hold dual arterial phase acquisition
      during gadoxetic acid-enhanced MRI reliably offers well-timed hepatic arterial
      phase with less respiratory motion artifact. However, a 13-second breath-hold
      single arterial phase acquisition was most effective in reducing respiratory
      motion artifact.

PMID- 28441160
TI  - Evidence-Based Practice and U.S. Healthcare Outcomes: Findings From a National
      Survey With Nursing Professional Development Practitioners.
AB  - Nursing professional development (NPD) practitioners are integral to implementing
      evidence-based practice (EBP). Research was conducted to describe NPD
      practitioners' EBP beliefs and competencies, frequency of implementing EBP, and
      perceptions of organizational culture and readiness for EBP. Relationships among
      NPD practitioner characteristics and organization outcomes were explored.
      Findings indicate that NPD practitioners must develop personal competence in EBP,
      become engaged in shared governance, collaborate with others, and use quality
      metrics to demonstrate the effectiveness and value of NPD activities.

PMID- 28441161
TI  - Policy brief tackles scope of practice laws and their impact.

PMID- 28441162
TI  - Managing herpes zoster in older adults: Prescribing considerations.
AB  - NPs must be aware of special prescribing considerations for medication safety
      when managing the care of older adults with herpes zoster. Age-related
      physiologic changes of the body impact the pharmacokinetics and pharmacodynamics
      of antiviral and pain medications and can lead to potential adverse events.

PMID- 28441163
TI  - Recognizing type 1 diabetes mellitus in children & adolescents.
AB  - The common chief complaint of abdominal pain, nausea, and vomiting should prompt
      a broad differential diagnosis list. When a 17-year-old previously healthy male
      presented to a primary care clinic with these symptoms, it provoked a detailed
      workup and found a startling diagnosis of type 1 diabetes mellitus (T1DM). This
      article provides an overview of recognizing T1DM in children and adolescents with
      a thorough and diagnostic evaluation.

PMID- 28441164
TI  - Information Acquisition Differences between Experienced and Novice Time Trial
      Cyclists.
AB  - PURPOSE: To use eye-tracking technology to directly compare information
      acquisition behavior of experienced and novice cyclists during a self-paced, 10
      mile (16.1 km) time trial (TT). METHOD: Two groups of novice (n = 10) and
      experienced cyclists (n = 10) performed a 10-mile self-paced TT on two separate
      occasions during which a number of feedback variables (speed, distance, power
      output, cadence, HR, and time) were projected within their view. A large RPE
      scale was also presented next to the projected information and participants.
      Participants were fitted with a head-mounted eye tracker and HR monitor. RESULTS:
      Experienced cyclists performed both TT quicker than novices (F1,18 = 6.8, P =
      0.018) during which they primarily looked at speed (9 of 10 participants),
      whereas novices primarily looked at distance (6 of 10 participants). Experienced
      cyclists looked at primary information for longer than novices across the whole
      TT (24.5% +/- 4.2% vs 34.2% +/- 6.1%; t18 = 4.2; P < 0.001) and less frequently
      than novices during the last quarter of the TT (49 +/- 19 vs 80 +/- 32; t18 = 
      2.6; P = 0.009). The most common combination of primary and secondary information
      looked at by experienced cyclists was speed and distance, respectively. Looking
      at 10 different primary-secondary feedback permutations, the novices were less
      consistent than the experienced cyclists in their information acquisition
      behavior. CONCLUSIONS: This study challenges the importance placed on knowledge
      of the endpoint to pacing in previous models, especially for experienced cyclists
      for whom distance feedback was looked at secondary to, but in conjunction with,
      information about speed. Novice cyclists have a greater dependence on distance
      feedback, which they look at for shorter and more frequent periods than the
      experienced cyclists. Experienced cyclists are more selective and consistent in
      attention to feedback during TT cycling.

PMID- 28441166
TI  - Minimally Invasive, Organ-preserving Surgery for Large Submucosal Tumors in the
      Abdominal Esophagus.
AB  - BACKGROUND: Surgical resection of submucosal tumors (SMTs) in the abdominal
      esophagus is not standardized. Enucleation may be a minimally invasive option,
      whereas its oncological validity is not very clear. Moreover, how to treat the
      esophageal wall defect after enucleation and necessity of additional antireflux
      procedure are also undetermined. METHODS: In 13 patients with a SMT originating
      the abdominal esophagus laparoscopic enucleation was performed with preserving
      the integrity of submucosa. When the muscular layer defect was <4 cm it was
      directly closed by suturing, whereas it was left open in case the defect was
      larger. Fundoplication was added when the esophagus was dissected posteriorly or
      the myotomy was not closed. RESULTS: Tumors were resected en-bloc without rupture
      in all cases. In 5 patients myotomy was closed, whereas in the remaining 8 it was
      left open. In 11 patients fundoplication was added (Toupet in 5 and Dor in 6).
      The patients developed neither regurgitation nor stenosis postoperatively. The
      histopathologic findings revealed leiomyoma in 9 patients, whereas the other 4
      were miscellaneous. The average tumor size was 5.5 cm (range, 2.8 to 8.8).
      Microscopically surgical margin was negative in all cases. CONCLUSIONS:
      Laparoscopic enucleation of SMTs in the abdominal esophagus seems to be safe,
      reproducible operation enabling preservation of function of the lower esophagus
      and esophagogastric junction. Even when the muscular defect is not approximated
      additional fundoplication can minimize the risk of postoperative reflux disease.

PMID- 28441167
TI  - Technical and Survival Risks Associated With Esophagojejunostomy by Laparoscopic
      Total Gastrectomy for Gastric Carcinoma.
AB  - BACKGROUND: We performed esophagojejunostomy after totally laparoscopic total
      gastrectomy (TLTG) using functional end-to-end anastomosis (FEEA) as the first
      choice and laparoscopic-assisted total gastrectomy (LATG) using a circular
      stapler with a transorally inserted anvil as the second choice. PATIENTS AND
      METHODS: We examined 109 patients with gastric cancer who underwent TLTG and
      LATG. Among these, 100 patients underwent TLTG and the rest underwent LATG.
      RESULTS: The length of resected esophageal segment in LATG patients was
      significantly longer than that in TLTG patients (P<0.001). The length of the
      resected esophagus segment was inversely correlated with body mass index in cases
      of esophagojejunostomy by FEEA (P<0.05). Multivariate analysis revealed that T
      factor, N factor, and severe complications were the independent factors for
      survival. CONCLUSIONS: Esophagojejunostomy using FEEA or a circular stapler with
      a transorally inserted anvil should be selected according to the length of the
      resected esophageal segment and/or body mass index.

PMID- 28441168
TI  - A review of caffeine use as a risk or protective factor for women's health and
      pregnancy.
AB  - PURPOSE OF REVIEW: To provide a narrative synthesis of recently published studies
      on caffeine use as a risk or protective factor for health outcomes, with a focus
      on women's health and pregnancy. RECENT FINDINGS: Based on predominantly
      observational studies, moderate caffeine intake has been shown to be a protective
      factor for liver cancer, certain bowel conditions, colorectal cancer, skin
      cancer, and regular menstrual cycle function. However, heavy consumption is a
      risk factor for osteoporosis, urinary incontinence, and poorer birth and child
      developmental outcomes. Residual confounding and issues surrounding retrospective
      self-reported intake are cited as key limitations in the majority of these
      studies. Moderate caffeine intake has been associated with lower risk of
      cardiovascular disease and metabolic syndrome; however, recent genetic
      epidemiology studies provide no evidence for a causal relationship. SUMMARY:
      Greater inclusion of female participants in studies, and analysis of sex
      differences in the relationship between caffeine intake and certain health
      conditions, is necessary. The current literature suggests caffeine's role as a
      risk or protective factor differs across health conditions. Often, there are
      plausible biological mechanisms for this relationship. However, a continued
      precautionary stance is recommended until direct causal pathways are established.
      Review of recently published studies does not suggest that current intake
      guidelines for adults and for pregnant woman need to be modified.

PMID- 28441169
TI  - Psychosocial interventions in stimulant use disorders: a focus on women.
AB  - PURPOSE OF REVIEW: Stimulant use disorders are significant contributors to the
      global burden of disease, with a growing impact on women. Psychosocial
      interventions are the gold standard for treating this condition, but several
      barriers may prevent women from accessing appropriate treatment. Therefore, we
      systematically reviewed the most recent findings about psychosocial interventions
      for stimulant use disorders, focussing on results relevant to women. RECENT
      FINDINGS: Twenty-two eligible studies were identified. Psychosocial interventions
      in stimulant use disorders were examined in 17 recent studies, but no analyses
      for sex-related differences were performed. These aspects were investigated in
      further five studies, either through secondary analyses on the female subgroup or
      specifically examining a female-only sample. Contingency management, either alone
      or in combination with other interventions, provided the most positive results on
      several outcome measures. Only one pilot study showed good potential for an
      alternative approach of systemic family therapy, warranting further research in
      this direction. SUMMARY: Research in stimulant use disorders shows an increasing
      interest in exploring interventions capable of addressing sex-specific issues.
      Combined therapy including contingency management and other treatments appears
      the most promising option, but larger secondary studies are needed to rank the
      efficacy of different psychosocial interventions while considering their
      feasibility and acceptability in specific subpopulations, including women.

PMID- 28441170
TI  - Provision of arts therapies for people with severe mental illness.
AB  - PURPOSE OF REVIEW: Arts therapies are still inadequately regulated throughout the
      world despite a 100-year-long tradition, a vast number of academically trained
      therapists and importance in treating psychiatric patients. It is essential that
      more evidence-based studies are undertaken. RECENT FINDINGS: Current
      international guidelines focus on the efficacy and effectiveness of arts
      therapies. New international evidence-based studies reporting clear-cut
      therapeutic effects of art therapy, music therapy and dance movement therapy are
      described here, with a focus on developments in Australia, Egypt and the United
      States. SUMMARY: Further effort must be put into the development of evidence
      based treatment programmes for all arts therapies, and effort needs to go into
      the establishment of arts therapists as a profession, with appropriate training
      standards.

PMID- 28441171
TI  - Prevalence of psychopathology in children of parents with mental illness and/or
      addiction: an up to date narrative review.
AB  - PURPOSE OF REVIEW: Children of parents with a mental illness and/or addiction are
      at high risk for developing a mental illness themselves. Parental mental illness
      is highly prevalent leading to a serious number of children at high risk. The aim
      of this review is to give an up-to-date overview of psychopathology in children
      of parents with various mental illnesses and/or addiction, based on recent
      literature. RECENT FINDINGS: Worldwide, 15-23% of children live with a parent
      with a mental illness. These children have up to 50% chance of developing a
      mental illness. Parental anxiety disorder sets children at a more specific risk
      for developing anxiety disorder themselves, where children of parents with other
      mental illnesses are at high risk of a large variety of mental illnesses.
      Although preventive interventions in children of mentally ill parents may
      decrease the risk of problem development by 40%; currently, these children are
      not automatically identified and offered help. SUMMARY: This knowledge should
      encourage mental health services to address the needs of these children which
      requires strong collaboration between Child and Adolescent Mental Health Services
      and Adult Mental Health Services. Directions for further research would be to
      include both parents, allow for comorbidity and to look deeper into a broader
      variety of mental illnesses such as autism and personality disorder other than
      borderline.

PMID- 28441172
TI  - Intravascular ultrasound and outcomes after drug-eluting stent implantation.
AB  - There have been nine published randomized trials and 30 registry studies
      comparing intravascular ultrasound (IVUS)-guided drug-eluting stent implantation
      versus conventional angiographic guidance. These trials and registries have been
      evaluated and summarized in (i) eight meta-analyses that included from nine to 18
      registries and from one to seven randomized trials and (ii) four meta-analyses
      that included from three to eight randomized trials. Although with one exception
      no two meta-analyses have included the same trials or studies, in each meta
      analysis, IVUS guidance was associated with a reduction in major adverse cardiac
      events as well as secondary hard endpoints of death (primarily cardiovascular
      mortality), myocardial infarction, and stent thrombosis, especially in randomized
      trial meta-analyses. This was explained in three meta-analyses comparing the
      acute results of IVUS versus angiographic guidance showing that (i) postdilation
      was used more frequently, and stent sizes, final angiographic minimum lumen
      diameters, and IVUS minimum stent areas were larger with IVUS guidance to
      minimize stent underexpansion and (ii) more stents were implanted and stents were
      longer with IVUS guidance to minimize geographic miss and treat edge dissections.
      IVUS-guided stent implantation can be used to minimize contrast during stent
      implantation, a strategy that is especially useful in patients with underlying
      renal insufficiency. Finally, an economic analysis showed that IVUS guidance was
      a dominant and cost-effective strategy, especially in patients with comorbid
      conditions who were at a higher risk of cardiac events and especially when the
      benefits of IVUS continued beyond 1 year.

PMID- 28441173
TI  - Religiosity in Acute Psychiatric Inpatients: Relationship With Demographics,
      Clinical Features, and Length of Stay.
AB  - This study examined the relationship between religiosity in 175 psychiatric
      inpatients as measured by the subscales of the Duke University Religion Index
      (DUREL) and sociodemographic (age, sex, and race), clinical (primary diagnosis,
      suicidality, and psychotic symptoms), and outcome (length of stay [LOS] and
      readmission rates) measures. Psychosis was assessed by Clinician-Rated Dimensions
      of Psychosis Symptom Severity (CRDPSS) scale. Bivariate and multivariate analyses
      were used to examine the association between the DUREL subscales and the outcome
      measures. High scorers on the nonorganized religiosity subscale were less likely
      to have psychosis (47% vs. 52%; p < 0.05) but had greater psychosis severity
      (mean +/- SD, 14.5 +/- 5 vs.12.4 +/- 6; p < 0.05), as measured by the CRDPSS
      scale, and significantly longer LOS (mean +/- SD, 8.3 +/- 3.8 vs. 6.9 +/- 3.4; p
      < 0.05). Conversely, they were less likely to report previous suicide attempts
      than low scorers (p < 0.05). These results suggest that a brief measure of
      religious activities may identify psychiatric inpatients at greater risk for
      psychosis, suicidality, and longer hospitalizations.

PMID- 28441174
TI  - Increased incidence of cancer observed in HIV/hepatitis C virus-coinfected
      patients versus HIV-monoinfected.
AB  - BACKGROUND: Cancer is a growing problem in persons living with HIV infection
      (PLWH) and hepatitis C virus (HCV) coinfection could play an additional role in
      carcinogenesis. Herein, all cancers in an HIV-mono and HIV/HCV-coinfected cohort
      were evaluated and compared to identify any differences between these two
      populations. METHODS: A retrospective cohort study was conducted including all
      cancers in PLWH between 1993 and 2014. Cancers were classified in two groups:
      AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC). Cancer incidence
      rates were calculated and compared with that observed in the Spanish general
      population (GLOBOCAN, 2012), computing the standardized incidence ratios (SIRs).
      A competing risk approach was used to estimate the probability of cancer after
      HIV diagnosis. Cumulative incidence in HIV-monoinfected and HIV/HCV-coinfected
      patients was also compared using multivariable analysis. RESULTS: A total of 185
      patients (117 HIV-monoinfected and 68 HIV/HCV) developed cancer in the 26 580
      patient-years cohort, with an incidence rate of 696 cancers per 100 000 person
      years, higher than in the general population (SIR = 3.8). The incidence rate of
      NADC in HIV/HCV-coinfected patients was 415.0 (SIR = 3.4), significantly higher
      than in monoinfected (377.3; SIR = 1.8). After adjustments, HIV/HCV-coinfected
      patients had a higher cumulative incidence of NADC than HIV-monoinfected
      (adjusted hazard ratio = 1.80), even when excluding hepatocellular carcinomas
      (adjusted hazard ratio = 1.26). CONCLUSION: PLWH have a higher incidence of NADC
      than the general population and HCV-coinfection is associated with a higher
      incidence of NADC. These data justify the need for prevention strategies in these
      two populations and the importance of eradicating HCV.

PMID- 28441175
TI  - Acceptability and use of a dapivirine vaginal ring in a phase III trial.
AB  - BACKGROUND: The MTN-020/ASPIRE trial evaluated the safety and effectiveness of
      the dapivirine vaginal ring for prevention of HIV-1 infection among African
      women. A nested qualitative component was conducted at six of 15 study sites in
      Uganda, Malawi, Zimbabwe and South Africa to evaluate acceptability of and
      adherence to the ring. METHOD: Qualitative study participants (n = 214) were
      interviewed with one of three modalities: single in-depth interview, up to three
      serial interviews or an exit Focus Group Discussion. Using semistructured guides
      administered in local languages, 280 interviews were audio-recorded, transcribed,
      translated, coded and analyzed. RESULTS: We identified three key findings: first,
      despite initial fears about the ring's appearance and potential side effects,
      participants grew to like it and developed a sense of ownership of the ring once
      they had used it. Second, uptake and sustained adherence challenges were
      generally overcome with staff and peer support. Participants developed gradual
      familiarity with ring use through trial progression, and most reported that it
      was easy to use and integrate into their lives. Using the ring in ASPIRE was akin
      to joining a team and contributing to a broader, communal good. Third, the actual
      or perceived dynamics of participants' male partner relationship(s) were the most
      consistently described influence (which ranged from positive to negative) on
      participants' acceptability and use of the ring. CONCLUSION: It is critical that
      demonstration projects address challenges during the early adoption stages of
      ring diffusion to help achieve its potential public health impact as an
      effective, long-acting, female-initiated HIV prevention option addressing women's
      disproportionate HIV burden.

PMID- 28441177
TI  - Right hip and bilateral shoulder capsulitis in an HIV-infected individual treated
      with elvitegravir and cobicistat.

PMID- 28441178
TI  - Unmet needs persist in pediatric HIV programs: lessons from selected case studies
      in Uganda.

PMID- 28441176
TI  - Long-term nitrite inhalant exposure and cancer risk in MSM.
AB  - OBJECTIVES: Nitrite inhalants (poppers) are commonly used recreational drugs
      among MSM and were previously associated with elevated rates of high-risk sexual
      behavior, HIV and human herpesvirus type 8 (HHV-8) seroconversion, and transient
      immunosuppressive effects in experimental models. Whether long-term popper use is
      associated with cancer risk among MSM in the HAART era is unclear. DESIGN:
      Prospective cohort study of cancer risk in 3223 HIV-infected and uninfected MSM
      in the Multicenter AIDS Cohort Study from 1996-2010. METHODS: Poisson regression
      models were used to examine the association between heavy popper use (defined as
      daily or weekly use for at least 1 year) and risk of individual cancers or
      composite category of virus-associated cancers. RESULTS: Among all participants,
      heavy popper use was not associated with increased risk of any individual
      cancers. Among HIV-uninfected men aged 50-70, heavy popper use was associated
      with increased risk of virus-associated cancer with causes linked to human
      papillomavirus, HHV-8, and Epstein-Barr virus in models adjusted for
      demographics, number of sexual partners, immunological parameters (CD4 cell
      counts or CD4/CD8 ratios), and hepatitis B and C viruses [incidence rate ratio
      (IRR), 95% confidence interval (CI) 3.24, 1.05-9.96], or sexually transmitted
      infections (IRR 3.03, 95% CI, 1.01-9.09), as was cumulative use over a 5-year
      period (IRR 1.012, 95% CI 1.003-1.021; P = 0.007). There was no significant
      association between heavy popper use and virus-associated cancer in HIV-infected
      men. CONCLUSIONS: Long-term heavy popper use is associated with elevated risk of
      some virus-associated cancers with causes related to human papillomavirus, HHV-8,
      and Epstein-Barr virus infections in older HIV-uninfected MSM independent of
      sexual behavior and immunological parameters.

PMID- 28441179
TI  - Kidney transplant outcomes in HIV serodiscordant recipient pairs.

PMID- 28441180
TI  - Neuropsychiatric adverse effects on dolutegravir: an emerging concern in Europe.

PMID- 28441182
TI  - From the Editor.

PMID- 28441183
TI  - Case in Health Care Management.

PMID- 28441181
TI  - Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous
      Breathing Using Two Different Nebulizers.
AB  - OBJECTIVES: To determine the feasibility of delivering inhaled treprostinil
      during mechanical ventilation and spontaneous unassisted ventilation using the
      Tyvaso Inhalation System and the vibrating mesh nebulizer. We sought to compare
      differences in fine particle fraction, and absolute inhaled treprostinil mass
      delivered to neonatal, pediatric, and adult models affixed with a face mask,
      conventional, and high-frequency ventilation between Tyvaso Inhalation System and
      with different nebulizer locations between Tyvaso Inhalation System and vibrating
      mesh nebulizer. DESIGN: Fine particle fraction was first determined via impaction
      with both the Tyvaso Inhalation System and vibrating mesh nebulizer. Next, a test
      lung configured with neonatal, pediatric, and adult mechanics and a filter to
      capture medication was attached to a realistic face model during spontaneous
      breathing or an endotracheal tube during conventional ventilation and high
      frequency oscillator ventilator. Inhaled treprostinil was then nebulized with
      both the Tyvaso Inhalation System and vibrating mesh nebulizer, and the filter
      was analyzed via high-performance liquid chromatography. Testing was done in
      triplicate. Independent two-sample t tests were used to compare mean fine
      particle fraction and inhaled mass between devices. Analysis of variance with
      Tukey post hoc tests were used to compare within device differences. SETTING:
      Academic children's hospital aerosol research laboratory. MEASUREMENTS AND MAIN
      RESULTS: Fine particle fraction was not different between the Tyvaso Inhalation
      System and vibrating mesh nebulizer (0.78 +/- 0.04 vs 0.77 +/- 0.08,
      respectively; p = 0.79). The vibrating mesh nebulizer delivered the same or
      greater inhaled treprostinil than the Tyvaso Inhalation System in every simulated
      model and condition. When using the vibrating mesh nebulizer, delivery was
      highest when using high-frequency oscillator ventilator in the neonatal and
      pediatric models, and with the nebulizer in the distal position in the adult
      model. CONCLUSIONS: The vibrating mesh nebulizer is a suitable alternative to the
      Tyvaso Inhalation System for inhaled treprostinil delivery. Fine particle
      fraction is similar between devices, and vibrating mesh nebulizer delivery meets
      or exceeds delivery of the Tyvaso Inhalation System. Delivery for infants and
      children during high-frequency oscillator ventilator with the vibrating mesh
      nebulizer may result in higher than expected dosages.

PMID- 28441186
TI  - Learning About Systems to Improve Health by Turning Problems Into Solutions.

PMID- 28441187
TI  - A Proposal for Avoiding Bias in Medical School Admissions Decisions.

PMID- 28441185
TI  - Exploring factors associated with patients' adherence to antihypertensive drugs
      among people with primary hypertension in the United Kingdom.
AB  - OBJECTIVE: To explore factors associated with adherence to antihypertensive drugs
      overall (therapy adherence) and to particular classes (class adherence) in
      hypertensive patients. METHODS: The current retrospective cohort study included
      adults with primary hypertension identified in the UK Clinical Practice Research
      Datalink from April 2006 to March 2013. Individuals were followed from the date
      of first-ever antihypertensive drug class (class adherence) prescribed and from
      the date of the first-ever antihypertensive drug (therapy adherence) issued to
      the earliest of study end, patient leaving the database, or death. Prescribing
      episodes (time from a drug class being first prescribed to the end of follow-up
      time) of six antihypertensive drug classes were recorded. Proportion of days
      covered (PDC) was used to estimate therapeutic adherence for a patient's
      antihypertensive drugs therapy during follow-up period and class adherence of a
      specific antihypertensive class in each episode, respectively. Generalized linear
      modelling was used to examine factors associated with PDC. RESULTS: Median
      therapy and class PDC were 93.9 and 98.3% in the 176 835 patients and 371 605
      prescribing episodes; 20 and 38.4% of the patients and episodes had PDC less than
      80%, respectively. Higher therapy and class PDC was associated with increasing
      age, using renin angiotensin drugs, and being preexisting patient and user of
      antihypertensive drugs. Higher deprivation, multiple comorbidities, and switching
      of antihypertensive drugs were associated with lower PDC. CONCLUSION: Several
      patient factors were confirmed as determinant of adherence to antihypertensive
      drug classes and therapy; hence, they can assist in identifying patients at risks
      of nonadherence, thus targeting them for adherence improving interventions.

PMID- 28441188
TI  - In Reply to Hubbeling.

PMID- 28441189
TI  - More on Medical Education in Africa.

PMID- 28441190
TI  - More on Medical Education in Africa.

PMID- 28441191
TI  - In Reply to Ventres.

PMID- 28441192
TI  - Comparing Active and Passive Learning: What Does the Evidence Really Say?

PMID- 28441193
TI  - In Reply to Willett.

PMID- 28441194
TI  - Scholarships for Humanism.

PMID- 28441195
TI  - The Things We Take for Granted.

PMID- 28441196
TI  - Losing Our Compassion.

PMID- 28441197
TI  - Considering Cocreation for the Choosing Wisely List.

PMID- 28441198
TI  - Changing the Paradigm of Meaningful Patient Involvement in Medical Education.

PMID- 28441199
TI  - Back to Basics.

PMID- 28441200
TI  - A Call for Residents to Get More Involved With Student-Run Free Clinics.

PMID- 28441201
TI  - Man Versus Machine: The Future of Medicine.

PMID- 28441202
TI  - Learning in the Era of Automation.

PMID- 28441203
TI  - The Pervasive Culture of Abuse in Medical Education: A Focus on Developing
      Countries.

PMID- 28441204
TI  - Contemporaries, Attitude, and Gratitude: Making the Most of a Medical School
      Experience.

PMID- 28441205
TI  - The Weaponization of Medical Professionalism.

PMID- 28441206
TI  - The Cross-Cockpit Authority Gradient in Medical Teaching.

PMID- 28441207
TI  - The Time to Grieve: A Difficult Question in Medical Training.

PMID- 28441208
TI  - The Modern Iteration of the House Call.

PMID- 28441209
TI  - The Stranger in the Room.

PMID- 28441211
TI  - I Can't Help the Way I Feel.

PMID- 28441210
TI  - Artist's Statement: Inde Ma'iingan (Heart of the Wolf).

PMID- 28441212
TI  - Commentary on I Can't Help the Way I Feel.

PMID- 28441213
TI  - The Role of Denosumab in the Modern Treatment of Giant Cell Tumor of Bone.

PMID- 28441214
TI  - The osteo-odonto-keratoprosthesis.
AB  - PURPOSE OF REVIEW: To describe the practice of and recent developments in the
      osteo-odonto-keratoprosthesis. RECENT FINDINGS: Formal psychological assessment
      and support have been described. A sub-aqua system for fashioning the osteo
      odonto-keratoprosthesis lamina; adoption of thicker laminae; use of
      bisphosphonate drugs; advances in laminar imaging; and use of bone augmentation
      and bone morphogenetic protein have been described for prevention, detection, and
      management of laminar resorption. Two systems of optical cylinders available
      commercially. A stepladder approach to buccal mucous membrane overgrowth onto the
      optical cylinder has been described, including use of mitomycin-C. Orbital
      decompression has been used for cosmetic improvement. Detection of glaucoma may
      be aided by an intraocular pressure sensor, whereas surgical treatment is mainly
      by way of glaucoma drainage devices, as endolaser ciliary ablation and recti
      muscle disinsertion and reinsertion not having prolonged and significant long
      term beneficial effect. Sublingual timolol has been described. The use of
      endoscopy has been proposed for preoperative evaluation of the posterior segment,
      ciliary ablation and for vitreoretinal surgery although wide-angle viewing
      systems remains standard practice. SUMMARY: The osteo-odonto-keratoprosthesis is
      the procedure of choice for rehabilitation of corneal blindness for end-stage
      ocular surface disease, serving a completely different patient group to the
      Boston Type 1 KPro.

PMID- 28441215
TI  - Does low-dose methotrexate deserve more respect from clinicians?
AB  - Medical errors associated with low-dose methotrexate may be life-threatening.
      Prescribers should be cognizant of the medication's toxicities and the persistent
      challenges in preventing adverse events. This article reviews the properties of
      methotrexate and its common drug-drug interactions. Best practices from the
      Institute for Safe Medication Practices, aimed at reducing methotrexate errors,
      are highlighted.

PMID- 28441217
TI  - An unusual case of sepsis and petechial rash.
AB  - This article describes a man who presented to the ED in acute distress with signs
      and symptoms of sepsis, pneumonia, and a new petechial rash on his chest. He was
      eventually diagnosed with Rocky Mountain spotted fever. Aggressive treatment of
      sepsis and timely administration of empiric antibiotics were lifesaving in this
      situation.

PMID- 28441218
TI  - Research on the PA profession: The medical model shifts.
AB  - Physician assistant (PA)-focused research arose in response to the idea that an
      assistant to the busy physician could improve healthcare delivery. The process of
      answering questions about the profession has involved multiple approaches and
      various scholarly disciplines. In the course of this undertaking, what emerged
      were three stages of examination of PA behavior. The bibliographic span from this
      period contains about 2,400 studies that advance some notion of PA benefit to
      society. On the 50th anniversary of the PA profession, a question arises as to
      what research has shown. The answer is that PAs are providing care at significant
      levels of quality and quantity and their presence is enriching many challenges in
      healthcare delivery. In an era where demand for medical services is outstripping
      supply, the good idea born in the 1960s is emerging as a medical innovation
      domestically and globally.

PMID- 28441219
TI  - Last but not least: PA practice in Mississippi.
AB  - This article describes the history of physician assistants (PAs) in Mississippi,
      the last state to pass legislation allowing for PA practice. A small group of PAs
      in the state began pursuing a PA practice act in the early 1990s with little
      political advocacy experience, and in 1994, the American Academy of PAs actively
      joined "The Battle for Mississippi." In April 2000, after years of PA advocacy,
      Mississippi passed the bill that would authorize PA practice in the state.

PMID- 28441220
TI  - Stroke.

PMID- 28441221
TI  - Abdominal trauma in an adolescent.

PMID- 28441222
TI  - What is causing this woman's altered mental status?

PMID- 28441223
TI  - Say goodnight.

PMID- 28441224
TI  - Paying attention.

PMID- 28441225
TI  - Recognizing common parasitic infestations.
AB  - Parasitic infestations commonly are seen in patients in primary care, urgent
      care, and EDs. These infestations are a common cause of pruritus and may lead to
      secondary infestations. This article reviews the signs and symptoms of pinworms,
      lice, bedbug, and scabies infestations, as well as diagnosis and appropriate
      treatment.

PMID- 28441226
TI  - Patient satisfaction with PAs in the Netherlands.
AB  - Physician assistants (PAs) were introduced in the Netherlands in 2002 and are now
      widely deployed. However, little is known about patient satisfaction with Dutch
      PAs. A comparative study of patient satisfaction was undertaken in the primary
      care setting. Patients seen by general practitioners (GPs) and PAs were surveyed
      using the Consumer Quality Index, a European quality survey instrument. Quality
      of performance indicators included patient satisfaction, effectiveness of
      treatment, and safety of treatment. The results found that few differences
      emerged, and Dutch patients appear to be as satisfied with the care received by
      PAs as with GPs.

PMID- 28441227
TI  - Three PAs talk about success in Mississippi.
AB  - This article gives the first-hand perspectives of three physician assistants
      (PAs) involved in the profession's years of struggle to gain practice authority
      in Mississippi. Through a series of questions and answers, each PA describes his
      or her part in the historical events that made Mississippi the final US state to
      regulate PAs.

PMID- 28441229
TI  - Preliminary Model for the Design of a Custom Middle Ear Prosthesis.
AB  - HYPOTHESIS: Custom prostheses could be used to recreate the ossicular chain and
      improve hearing. BACKGROUND: Ossicular discontinuity or fixation occurs in 55% of
      cases of conductive hearing loss, with most cases involving the incus.
      Reconstruction has been achieved by a variety of methods; however, there has been
      little improvement in hearing outcomes in decades. METHODS: Precise measurements
      of anatomic dimensions, weight, and center of gravity were taken from 19
      cadaveric incudes. These measurements were combined with measurements from the
      medical literature and micro-computed tomography (micro-CT) of cadaveric temporal
      bones to generate a rasterizable incus model. As a proof of concept, incudal
      replacements including possible anatomic variations were then three-dimensionally
      (3-D) printed and inserted into a cadaveric temporal bone. RESULTS: Our
      measurements of cadaveric incudes corresponded well with those from the medical
      literature. These measurements were combined with anatomical information from
      micro-CT allowing identification of critical features of the incus, which
      remained constant. Other model features were modified to increase stability and
      facilitate synthesis, including broadening and thickening of the lenticular
      process and the incudomalleolar articulation. 3-D printed incudal replacements
      based on this model readily fit into a cadaveric temporal bone and successfully
      bridged the gap between malleus and incus. CONCLUSION: We have generated a model
      for custom 3-D synthesis of incudal prostheses. While current 3-D printing in
      biocompatible materials at the size required is limited, the technology is
      rapidly advancing, and 3-D printing of incudal replacements with polylactic acid
      (PLA) is of the correct size and shape.

PMID- 28441230
TI  - Cochlear Implantation in Adults With Asymmetric Hearing Loss: Benefits of Bimodal
      Stimulation.
AB  - OBJECTIVE: This study addresses the outcome of cochlear implantation in addition
      to hearing aid use in patients with asymmetric sensorineural hearing loss. STUDY
      DESIGN: Prospective longitudinal study. SETTING: Tertiary referral center.
      PATIENTS: Seven adults with asymmetric sensorineural hearing loss, i.e., less
      than 30% aided speech recognition in their worst hearing ear and 60 to 85% speech
      recognition in their best hearing ear. All patients had a postlingual onset of
      their hearing loss and less than 20 years of auditory deprivation of their worst
      hearing ear. INTERVENTION: Cochlear implantation in the functionally deaf ear.
      MAIN OUTCOME MEASURES: Speech recognition in quiet, speech recognition in noise,
      spatial speech recognition, localization abilities, music appreciation, and
      quality of life. Measurements were performed before cochlear implantation and 3,
      6, and 12 months after cochlear implantation. RESULTS: Before cochlear
      implantation, the average speech recognition of the ear fitted with a hearing aid
      was 74%. Cochlear implantation eventually resulted in an average speech
      recognition of 75%. Bimodal stimulation yielded speech recognition scores of 82,
      86, and 88% after 3, 6, and 12 months, respectively. At all time intervals,
      bimodal stimulation resulted in a significantly better speech recognition as
      compared with stimulation with only hearing aid or only cochlear implant (CI).
      Speech recognition in noise and spatial speech recognition significantly improved
      as well as the ability to localize sounds and the quality of life. CONCLUSION:
      This study demonstrated that patients are able to successfully integrate
      electrical stimulation with contralateral acoustic amplification and benefit from
      bimodal stimulation. Therefore, we think that cochlear implantation should be
      considered in this particular group of patients, even in the presence of
      substantial residual hearing on the contralateral side.

PMID- 28441231
TI  - Patient-Specific Classification of ICU Sedation Levels From Heart Rate
      Variability.
AB  - OBJECTIVE: To develop a personalizable algorithm to discriminate between sedation
      levels in ICU patients based on heart rate variability. DESIGN: Multicenter,
      pilot study. SETTING: Several ICUs at Massachusetts General Hospital, Boston, MA.
      PATIENTS: We gathered 21,912 hours of routine electrocardiogram recordings from a
      heterogenous group of 70 adult ICU patients. All patients included in the study
      were mechanically ventilated and were receiving sedatives. MEASUREMENTS AND MAIN
      RESULTS: As "ground truth" for developing our method, we used Richmond Agitation
      Sedation Scale scores grouped into four levels denoted "comatose" (-5), "deeply
      sedated" (-4 to -3), "lightly sedated" (-2 to 0), and "agitated" (+1 to +4). We
      trained a support vector machine learning algorithm to calculate the probability
      of each sedation level from heart rate variability measures derived from the
      electrocardiogram. To estimate algorithm performance, we calculated leave-one
      subject out cross-validated accuracy. The patient-independent version of the
      proposed system discriminated between the four sedation levels with an overall
      accuracy of 59%. Upon personalizing the system supplementing the training data
      with patient-specific calibration data, consisting of an individual's labeled
      heart rate variability epochs from the preceding 24 hours, accuracy improved to
      67%. The personalized system discriminated between light- and deep-sedation
      states with an average accuracy of 75%. CONCLUSIONS: With further refinement, the
      methodology reported herein could lead to a fully automated system for depth of
      sedation monitoring. By enabling monitoring to be continuous, such technology may
      help clinical staff to monitor sedation levels more effectively and to reduce
      complications related to over- and under sedation.

PMID- 28441232
TI  - Atriobronchial Fistula Complicated by Septic Cerebral Air Emboli After Pulmonary
      Vein Ablation.
AB  - OBJECTIVE: To describe a case of an infected atriobronchial fistula as a late
      complication after pulmonary vein ablation, leading to septic air emboli and
      requiring urgent cardiac surgery. DATA SOURCES: Clinical observation. STUDY
      SELECTION: Case report. DATA EXTRACTION: Relevant clinical information. PubMed
      was searched for relevant literature. DATA SYNTHESIS: Given its high success and
      low complication rate, pulmonary vein isolation is expected to be increasingly
      performed worldwide. Despite its success, some of its rare complications are
      potentially devastating and are difficult to diagnose early. In this report, we
      present the case of a 32-year-old woman, who was readmitted to hospital 2 months
      after pulmonary vein ablation. The clinical picture resembled meningococcemia
      with spreading petechiae on legs and arms raising concern for Waterhouse
      Friderichsen syndrome. Further echocardiographic investigation led to the
      discovery of massive amounts of intracardiac air which demanded urgent lung
      isolation and sternotomy. Intraoperatively a small infected left atrial
      perforation was oversewn and a fistula to the right main bronchus was closed by
      means of an autologous pericardial patch. One month later, still revalidating,
      she could be discharged home with only minor neurologic sequelae. CONCLUSIONS:
      Clinicians should be aware of the dramatic complications of invasive
      antiarrhythmic procedures and their atypical and late presentations. Better
      preprocedural appreciation of cardiac wall thickness, early echocardiographic
      diagnosis, and swift referral for cardiac surgery might impact outcome
      dramatically.

PMID- 28441233
TI  - Acute Respiratory Distress Syndrome Due To Tuberculosis in a Respiratory ICU Over
      a 16-Year Period.
AB  - OBJECTIVE: Whether tuberculosis-related acute respiratory distress syndrome is
      associated with worse outcomes when compared with acute respiratory distress
      syndrome secondary to other causes remains unknown. Herein, we compare the
      outcomes between the two groups. DESIGN: Retrospective analysis of all subjects
      admitted with acute respiratory distress syndrome over the last 16 years.
      SETTING: Respiratory ICU of a tertiary care hospital in North India. SUBJECTS:
      Consecutive subjects with acute respiratory distress syndrome. INTERVENTION:
      Subjects were categorized as tuberculosis-related acute respiratory distress
      syndrome and acute respiratory distress syndrome-others and were managed with
      mechanical ventilation using the low tidal volume strategy as per the Acute
      Respiratory Distress Syndrom Network protocol. MEASUREMENTS AND MAIN RESULTS: The
      baseline clinical and demographic characteristics, lung mechanics, and mortality
      were compared between the two groups. Factors predicting ICU survival were
      analyzed using multivariate logistic regression analysis. During the study
      period, 469 patients (18 tuberculosis-related acute respiratory distress syndrome
      and 451 acute respiratory distress syndrome-others) with acute respiratory
      distress syndrome were admitted. The mean (SD) age of the study population (52.9%
      women) was 33.6 years (14.8 yr). The baseline parameters and the lung mechanics
      were similar between the two groups. There were 132 deaths (28.1%) with no
      difference between the two groups (tuberculosis-related acute respiratory
      distress syndrome vs acute respiratory distress syndrome-others; 27.7% vs 28.2%;
      p = 0.71). There was also no significant difference in the ventilator-free days,
      ICU, and the hospital length of stay. On multivariate logistic regression
      analysis, the factors predicting survival were the admission Acute Physiology and
      Chronic Health Evaluation II score and baseline driving pressure after adjusting
      for PaO2:FIO2 ratio, gender, and the etiology of acute respiratory distress
      syndrome. CONCLUSIONS: Tuberculosis is an uncommon cause of acute respiratory
      distress syndrome even in high tuberculosis prevalence countries. Acute
      respiratory distress syndrome due to tuberculosis behaves like acute respiratory
      distress syndrome due to other causes and does not affect the ICU survival.

PMID- 28441234
TI  - Validation of an Administrative Definition of ICU Admission Using Revenue Center
      Codes.
AB  - OBJECTIVES: Describe the operating characteristics of a proposed set of revenue
      center codes to correctly identify ICU stays among hospitalized patients. DESIGN:
      Retrospective cohort study. We report the operating characteristics of all ICU
      related revenue center codes for intensive and coronary care, excluding nursery,
      intermediate, and incremental care, to identify ICU stays. We use a
      classification and regression tree model to further refine identification of ICU
      stays using administrative data. The gold standard for classifying ICU admission
      was an electronic patient location tracking system. SETTING: The University of
      Pennsylvania Health System in Philadelphia, PA, United States. PATIENTS: All
      adult inpatient hospital admissions between July 1, 2013, and June 30, 2015.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 127,680 hospital
      admissions, the proposed combination of revenue center codes had 94.6%
      sensitivity (95% CI, 94.3-94.9%) and 96.1% specificity (95% CI, 96.0-96.3%) for
      correctly identifying hospital admissions with an ICU stay. The classification
      and regression tree algorithm had 92.3% sensitivity (95% CI, 91.6-93.1%) and
      97.4% specificity (95% CI, 97.2-97.6%), with an overall improved accuracy (chi =
      398; p < 0.001). CONCLUSIONS: Use of the proposed combination of revenue center
      codes has excellent sensitivity and specificity for identifying true ICU
      admission. A classification and regression tree algorithm with additional
      administrative variables offers further improvements to accuracy.

PMID- 28441235
TI  - Noninvasive iPhone Measurement of Left Ventricular Ejection Fraction Using
      Intrinsic Frequency Methodology.
AB  - OBJECTIVE: The study is based on previously reported mathematical analysis of
      arterial waveform that extracts hidden oscillations in the waveform that we
      called intrinsic frequencies. The goal of this clinical study was to compare the
      accuracy of left ventricular ejection fraction derived from intrinsic frequencies
      noninvasively versus left ventricular ejection fraction obtained with cardiac
      MRI, the most accurate method for left ventricular ejection fraction measurement.
      DESIGN: After informed consent, in one visit, subjects underwent cardiac MRI
      examination and noninvasive capture of a carotid waveform using an iPhone camera
      (The waveform is captured using a custom app that constructs the waveform from
      skin displacement images during the cardiac cycle.). The waveform was analyzed
      using intrinsic frequency algorithm. SETTING: Outpatient MRI facility. SUBJECTS:
      Adults able to undergo MRI were referred by local physicians or self-referred in
      response to local advertisement and included patients with heart failure with
      reduced ejection fraction diagnosed by a cardiologist. INTERVENTIONS: Standard
      cardiac MRI sequences were used, with periodic breath holding for image
      stabilization. To minimize motion artifact, the iPhone camera was held in a
      cradle over the carotid artery during iPhone measurements. MEASUREMENTS AND MAIN
      RESULTS: Regardless of neck morphology, carotid waveforms were captured in all
      subjects, within seconds to minutes. Seventy-two patients were studied, ranging
      in age from 20 to 92 years old. The main endpoint of analysis was left
      ventricular ejection fraction; overall, the correlation between ejection fraction
      iPhone and ejection fraction-MRI was 0.74 (r = 0.74; p < 0.0001; ejection
      fraction-MRI = 0.93 * [ejection fraction-iPhone] + 1.9). CONCLUSIONS: Analysis of
      carotid waveforms using intrinsic frequency methods can be used to document left
      ventricular ejection fraction with accuracy comparable with that of MRI. The
      measurements require no training to perform or interpret, no calibration, and can
      be repeated at the bedside to generate almost continuous analysis of left
      ventricular ejection fraction without arterial cannulation.

PMID- 28441236
TI  - The New MIRUS System for Short-Term Sedation in Postsurgical ICU Patients.
AB  - OBJECTIVES: To evaluate the feasibility and safety of the MIRUS system (Pall
      International, Sarl, Fribourg, Switzerland) for sedation with sevoflurane for
      postsurgical ICU patients and to evaluate atmospheric pollution during sedation.
      DESIGN: Prospective interventional study. SETTING: Surgical ICU. February 2016 to
      December 2016. PATIENTS: Postsurgical patients requiring ICU admission,
      mechanical ventilation, and sedation. INTERVENTIONS: Sevoflurane was administered
      with the MIRUS system targeted to a Richmond Agitation Sedation Scale from -3 to 
      5 by adaptation of minimum alveolar concentration. MEASUREMENTS AND MAIN RESULTS:
      Data collected included Richmond Agitation Sedation Scale, minimum alveolar
      concentration, inspired and expired sevoflurane fraction, wake-up times, duration
      of sedation, sevoflurane consumption, respiratory and hemodynamic data,
      Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment,
      and laboratory data and biomarkers of organ injury. Atmospheric pollution was
      monitored at different sites: before sevoflurane delivery (baseline) and during
      sedation with the probe 15 cm up to the MIRUS system (S1) and 15 cm from the
      filter-Reflector group (S2). Sixty-two patients were enrolled in the study. No
      technical failure occurred. Median Richmond Agitation Sedation Scale was -4.5
      (interquartile range, -5 to -3.6) with sevoflurane delivered at a median minimum
      alveolar concentration of 0.45% (interquartile range, 0.4-0.53) yielding a mean
      inspiratory and expiratory concentrations of 0.79% (SD, 0.24) and 0.76% (SD,
      0.18), respectively. Median awakening time was 4 minutes (2.2-5 min). Median
      duration of sevoflurane administration was 3.33 hours (2.33-5.75 hr), range 1-19
      hours with a mean consumption of 7.89 mL/hr (SD, 2.99). Hemodynamics remained
      stable over the study period, and no laboratory data indicated liver or kidney
      injury or dysfunction. Median sevoflurane room air concentration was 0.10 parts
      per million (interquartile range, 0.07-0.15), 0.17 parts per million
      (interquartile range, 0.14-0.27), and 0.15 parts per million (interquartile
      range, 0.07-0.19) at baseline, S1, and S2, respectively. CONCLUSIONS: The MIRUS
      system is a promising and safe alternative for short-term sedation with
      sevoflurane of ICU patients. Atmospheric pollution is largely below the
      recommended thresholds (< 5 parts per million). Studies extended to more
      heterogeneous population of patients undergoing longer duration of sedation are
      needed to confirm these observations.

PMID- 28441237
TI  - Noninvasive Ventilation in Acute Hypoxemic Nonhypercapnic Respiratory Failure: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To evaluate the effectiveness of noninvasive ventilation in patients
      with acute hypoxemic nonhypercapnic respiratory failure unrelated to exacerbation
      of chronic obstructive pulmonary disease and cardiogenic pulmonary edema. DATA
      SOURCES: PubMed, EMBASE, Cochrane library, Web of Science, and bibliographies of
      articles were retrieved inception until June 2016. STUDY SELECTION: Randomized
      controlled trials comparing application of noninvasive ventilation with standard
      oxygen therapy in adults with acute hypoxemic nonhypercapnic respiratory failure
      were included. Chronic obstructive pulmonary disease exacerbation and cardiogenic
      pulmonary edema patients were excluded. The primary outcome was intubation rate;
      ICU mortality and hospital mortality were secondary outcomes. DATA EXTRACTION:
      Demographic variables, noninvasive ventilation application, and outcomes were
      retrieved. Internal validity was assessed using the risk of bias tool. The
      strength of evidence was assessed using Grading of Recommendations Assessment,
      Development, and Evaluation methodology. DATA SYNTHESIS: Eleven studies (1,480
      patients) met the inclusion criteria and were analyzed by using a random effects
      model. Compared with standard oxygen therapy, the pooled effect showed that
      noninvasive ventilation significantly reduced intubation rate with a summary risk
      ratio of 0.59 (95% CI, 0.44-0.79; p = 0.0004). Furthermore, hospital mortality
      was also significantly reduced (risk ratio, 0.46; 95% CI, 0.24-0.87; p = 0.02).
      Subgroup meta-analysis showed that the application of bilevel positive support
      ventilation (bilevel positive airway pressure) was associated with a reduction in
      ICU mortality (p = 0.007). Helmet noninvasive ventilation could reduce hospital
      mortality (p = 0.0004), whereas face/nasal mask noninvasive ventilation could
      not. CONCLUSIONS: Noninvasive ventilation decreased endotracheal intubation rates
      and hospital mortality in acute hypoxemia nonhypercapnic respiratory failure
      excluding chronic obstructive pulmonary disease exacerbation and cardiogenic
      pulmonary edema patients. There is no sufficient scientific evidence to recommend
      bilevel positive airway pressure or helmet due to the limited number of trials
      available. Large rigorous randomized trials are needed to answer these questions
      definitely.

PMID- 28441238
TI  - Diaphragm Activation in Ventilated Patients Using a Novel Transvenous Phrenic
      Nerve Pacing Catheter.
AB  - OBJECTIVES: Over 30% of critically ill patients on positive-pressure mechanical
      ventilation have difficulty weaning from the ventilator, many of whom acquire
      ventilator-induced diaphragm dysfunction. Temporary transvenous phrenic nerve
      pacing using a novel electrode-bearing catheter may provide a means to prevent
      diaphragm atrophy, to strengthen an atrophied diaphragm, and mitigate the harms
      of mechanical ventilation. We tested the initial safety, feasibility, and impact
      on ventilation of this novel approach. DESIGN: First-in-Humans case series.
      SETTING: Angiogram suite. PATIENTS: Twenty-four sedated, mechanically ventilated
      patients immediately prior to an elective atrial septal defect repair procedure.
      INTERVENTIONS: A 9.5-Fr central venous catheter with 19 embedded electrodes was
      placed via Seldinger technique into the left subclavian vein and superior vena
      cava and evaluated for up to 90 minutes. The electrode combinations determined to
      provide best transvenous stimulation of the right and left phrenic nerves were
      activated in synchrony with mechanically ventilated breaths. MEASUREMENTS AND
      MAIN RESULTS: One patient could not be tested for reasons unrelated to the
      device. In the 23 patients who underwent the full protocol, transvenous
      stimulation activated the diaphragm in 22 of 23 (96%) left phrenic capture
      attempts and 20 of 23 (87%) right phrenic capture attempts. In one subject, a
      congenital left-sided superior vena cava precluded right-sided capture.
      Significant reductions in ventilator pressure-time-product were achieved during
      stimulation assisted breaths in all 22 paced subjects (range, 9.9-48.6%; p <
      0.001). There were no adverse events either immediately or at 2-week follow-up.
      CONCLUSIONS: In this First-in-Human series, diaphragm pacing with a temporary
      catheter was safe and effectively contributed to ventilation in conjunction with
      a mechanical ventilator.

PMID- 28441239
TI  - Traumatic Abdominal Wall Hernia in Children by Handlebar Injury: When to Suspect,
      Scan, and Call the Surgeon.
AB  - Traumatic abdominal wall hernias (TAWHs) can be defined as a herniation through
      disrupted musculature and fascia associated with blunt trauma. They are seen in
      approximately 1% of patients with blunt abdominal trauma. Data on TAWH in the
      pediatric population are very limited and principally based on case reports and a
      few case series. Past reports have indicated that the presence of the "handlebar
      sign" confers an increased risk of internal injury. Concomitant internal injuries
      are reported with an incidence between 25% and 70%, and occult hernias may also
      occur and are usually detected only by abdominal computed tomography scan and
      ultrasonography. The treatment of TAWH consists in surgical exploration through
      closure of the defect. We describe 2 cases of TAWH due to blunt impact by bicycle
      handlebars that occurred in our department with a brief literature review. Our
      objectives are to describe the variable clinical presentations and management of
      these events. We hope to provide a useful tool for the clinician to increase
      early clinical suspicion and detection of this insidious injury.

PMID- 28441240
TI  - Emergency Department Management of Bronchiolitis in the United States.
AB  - OBJECTIVE: The aim of this study was to examine differences between general and
      pediatric emergency departments (PEDs) in adherence to the American Academy of
      Pediatrics bronchiolitis management guidelines. METHODS: We conducted a
      nationally representative study of ED visits by infants younger than 24 months
      with bronchiolitis from 2002 to 2011 using the National Hospital Ambulatory
      Medical Care Survey. Diagnostic testing (complete blood counts, radiographs) and
      medication use (albuterol, corticosteroids, antibiotics and intravenous fluids)
      in general emergency departments (GEDs) were compared with those in PEDs before
      and after 2006 American Academy of Pediatrics guideline publication. Weighted
      percentages were compared, and logistic regression evaluated the association
      between ED type and resource use. RESULTS: Of more than 2.5 million ED visits for
      bronchiolitis from 2002 to 2011, 77.3% occurred in GEDs. General emergency
      departments were more likely to use radiography (62.7% vs 42.1%; adjusted odds
      ratio [aOR], 2.4; 95% confidence interval [CI], 1.4-4.1), antibiotics (41.3% vs
      18.8%; aOR, 2.8; 95% CI, 1.5-5.2), and corticosteroids (24.3% vs 12.5%; aOR, 2.1;
      95% CI, 1.0-4.5) compared with PEDs. Compared with preguideline, after guideline
      publication PEDs had a greater decrease in radiography use (-19.7%; 95% CI, 
      39.3% to -0.03%) compared with GEDs (-12.2%; 95% CI, -22.3% to -2.1%), and PEDs
      showed a significant decline in corticosteroid use (-12.4%; 95% CI, -22.1% to 
      2.8%), whereas GEDs showed no significant decline (-4.6%; 95% CI, -13.5% to
      4.3%). CONCLUSIONS: The majority of ED visits for bronchiolitis in the United
      States occurred in GEDs, yet GEDs had increased use of radiography,
      corticosteroids, and antibiotics and did not show substantial declines with
      national guideline publication. Given that national guidelines discourage the use
      of such tests and treatments in the management of bronchiolitis, efforts are
      required to decrease ED use of these resources in infants with bronchiolitis,
      particularly in GEDs.

PMID- 28441241
TI  - Pelvic Inflammatory Disease in a Pediatric Emergency Department: Epidemiology and
      Treatment.
AB  - OBJECTIVES: Most adolescent cases of pelvic inflammatory disease (PID) are
      diagnosed in the emergency department (ED). An important step to prevent PID
      related morbidity among this high-risk population is to quantify prevalence and
      microbial patterns and identify testing and treatment gaps. METHODS: We performed
      a retrospective, cross-sectional study of all visits by adolescents to an urban
      children's ED with an International Classification of Diseases, Ninth Revision,
      diagnosis of PID in 2012. We used standard descriptive statistics to quantify PID
      diagnoses, sexually transmitted infections (STI) testing, and treatment. RESULTS:
      Pelvic inflammatory disease was diagnosed in more than 9% of women with a chief
      complaint of abdominal/pelvic pain. Most diagnosed cases underwent some STI
      testing, and 40% tested positive. Seventy percent of cases received antibiotics
      recommended by the Centers for Disease Control and Prevention. CONCLUSIONS: There
      is a high prevalence of PID among adolescents in the pediatric ED. Rates of STI
      testing and appropriate treatment reveal gaps in diagnosis and management,
      representing a lost opportunity for identification and treatment of PID/STIs
      among high-risk adolescents.

PMID- 28441242
TI  - Identifying Undiagnosed Pediatric Mental Illness in the Emergency Department.
AB  - BACKGROUND: It is well known that pediatric psychiatric patients frequent
      emergency department (ED), but the number of patients with undiagnosed
      psychiatric illness presenting to an ED is not well known. Identification and
      referral of these patients may provide an opportunity for improved patient care.
      The primary study objective was to identify a tool that can screen for
      unsuspected psychiatric illness in pediatric patients who present to the ED with
      non-psychiatric-related complaints. METHODS: The MINI International
      Neuropsychiatric Interview for Children and Adolescents screening tool was
      administered to 200 pediatric consenting patients and guardians. The inclusion
      criteria were English-speaking patients who presented in the ED with a
      nonpsychiatric complaint who were stable and able to communicate. The study was
      conducted in a level 1 trauma center ED of an inner-city hospital that serves a
      predominantly African American and Hispanic population. This study was
      institutional review board approved. RESULTS: The study populations consisted of
      53% African American (107), 45% Hispanic (90), 1% white (2), and 0.5% Asian (1).
      Their age range was divided, with 49% between 12 and 14 years (98) and 51%
      between 15 and 17 years (102). The sex was evenly split, with 50% male (100) and
      50% female (100). The 41% who did screen positive for an undiagnosed mental
      illness had a range of diagnoses. The top modules with positive results were
      oppositional defiant (13.5%, 27), attention-deficit/hyperactivity disorder (13%,
      25), depression (10%, 11), conduct disorder (9%, 19), and anxiety (5%, 11).
      CONCLUSIONS: The pediatric Mini International Neuropsychiatric Interview was
      effective in screening for undiagnosed mental illness in pediatric patients who
      presented to the ED with no psychiatric-related illness. The screening tool
      indicated that 41% of pediatric patients screened positive for an undiagnosed
      mental illness, with attention deficit-related disorders being the most widely
      seen. Further study should be conducted to test the tools used in a range of ED
      settings.

PMID- 28441243
TI  - Emergency Point-of-Care Ultrasound Diagnosis of Retained Soft Tissue Foreign
      Bodies in the Pediatric Emergency Department.
AB  - The presence of a foreign body (FB), its depth and size, is often indeterminate
      by clinical examination. Conventional imaging such as a radiograph can fail to
      visualize soft tissue FBs. We present 2 cases where point-of-care ultrasound was
      used to detect previously unidentified FBs.

PMID- 28441244
TI  - Zika Virus Infection.

PMID- 28441245
TI  - What to Expect When Thrombocytopenic Children Present With Domestic Head Injury?

PMID- 28441246
TI  - X-ray Imaging Analysis of Intrathecal Baclofen Pumps for Pediatric Emergency
      Medicine.
AB  - Intrathecal baclofen therapy has become increasingly popular because of its
      effectiveness in treating spasticity in pediatric patients. The device implanted
      into each patient is structurally similar. However, x-ray imaging can give the
      appearance of missing or extraneous objects on or near the intrathecal baclofen
      device. The composition of the material used in making the catheters is
      transparent on x-ray images. In addition, the connection port between the pump
      and catheter may resemble the shape of a needle. This has led to confusion among
      emergency room personnel, and unnecessary panic for other people involved. It is
      important that medical professionals understand many of the new designs of the
      pump-connector system to avoid further complications.

PMID- 28441248
TI  - Letter from the Editor.

PMID- 28441249
TI  - Epidemiology of Second Primary Tumors in Women With Ovarian Cancer.
AB  - OBJECTIVE: The last large study of second primary tumors (SPTs) in women with
      ovarian cancer was published in 1996, prior to major changes in the differential
      diagnosis and treatment. The present study reports on the incidence of SPTs in a
      contemporary cohort of patients with a diagnosis of ovarian cancer. METHODS:
      Ovarian cancer patients with a diagnosis of an ovarian malignancy between 1992
      and 2012 were identified and characterized from 13 registries of the
      Surveillance, Epidemiology, and End Results database. RESULTS: Of 41,073 women
      with a diagnosis of an ovarian malignancy between 1992 and 2012, 1831 (4.5%)
      developed a microscopically confirmed SPT. There was no significant difference in
      the risk of developing an SPT at all sites between women with an ovarian cancer
      and the general population. There was an elevated risk of site-specific SPTs of
      the small intestine, vagina, thyroid gland, and acute nonlymphocytic leukemia in
      ovarian cancer patients compared with the general Surveillance, Epidemiology, and
      End Results population. Conversely, the risk of lung and non-Hodgkin lymphoma was
      significantly decreased in women with ovarian cancer. An elevated risk of SPTs
      was observed in women with mucinous, endometrioid, and germ cell tumors. White
      women had an overall decreased risk of developing a second primary solid tumor,
      whereas American Indian and Asian/Pacific Islander women had an overall increased
      risk of an SPT at any site. CONCLUSIONS: The incidence of SPTs in women with
      ovarian cancer was not significantly different as compared with the general
      population. However, divergent rates of SPTs in relation to histology, latency,
      age, and race were observed.

PMID- 28441250
TI  - A Comparison of Survival Outcomes in Advanced Serous Ovarian Cancer Patients
      Treated With Primary Debulking Surgery Versus Neoadjuvant Chemotherapy.
AB  - OBJECTIVE: The management of women with advanced-stage serous ovarian cancer
      includes a combination of surgery and chemotherapy. The choice of treatment with
      primary debulking surgery or neoadjuvant chemotherapy varies by institution. The
      objective of this study was to report 5-year survival outcomes for ovarian cancer
      patients treated at a single institution with primary debulking surgery or
      neoadjuvant chemotherapy. METHODS: This study included a retrospective chart
      review of 303 patients with stage IIIC or IV serous ovarian carcinoma diagnosed
      in Calgary, Canada. The patients were categorized into 1 of the 2 treatment arms:
      primary debulking surgery or neoadjuvant chemotherapy. The 5-year ovarian cancer
      specific survival rates were estimated using Kaplan-Meier curves. RESULTS: Among
      the 303 eligible patients, 142 patients (47%) underwent primary debulking
      surgery, and 161 patients (53%) were treated with neoadjuvant chemotherapy. Five
      year survival was better for patients undergoing primary debulking surgery (39%)
      than for patients who received neoadjuvant chemotherapy (27%; P = 0.02). Women
      with no residual disease experienced better overall survival than those with any
      residual disease (47% vs. 26%, respectively; P = 0.0002). This difference was
      significant for those who had primary debulking surgery (P = 0.0004) but not for
      the patients who received neoadjuvant chemotherapy (P = 0.09). Women who received
      intraperitoneal chemotherapy had better overall survival as compared with
      patients who received intravenous chemotherapy (44% vs 30%, respectively; P =
      0.002). CONCLUSIONS: Our findings suggest that among women with no residual
      disease, survival is better among those who undergo primary debulking surgery
      than treatment with neoadjuvant chemotherapy. The latter should be reserved for
      women who are deemed not to be candidates for primary debulking surgery.

PMID- 28441251
TI  - Prognostic Role of Histological Tumor Regression in Patients Receiving
      Neoadjuvant Chemotherapy for High-Grade Serous Tubo-ovarian Carcinoma.
AB  - OBJECTIVE: Our objective was to validate the prognostic role of the chemotherapy
      response score (CRS), which has been proposed for measuring tumor response to
      neoadjuvant chemotherapy in patients with high-grade serous tubo-ovarian
      carcinoma, in predicting progression-free survival (PFS) and overall survival
      (OS). METHODS: A retrospective cohort study was conducted of patients with
      advanced high-grade serous tubo-ovarian carcinoma diagnosed between January 1,
      2010, and December 31, 2014, and treated with neoadjuvant chemotherapy. Treatment
      related tumor regression was determined according to the 3-tier CRS, and results
      were compared with standard clinicopathological variables. Survival analysis was
      performed using Cox proportional hazards models and the log-rank test. RESULTS:
      Seventy-one patients were eligible for analysis. Median OS was 25.5 months. Fifty
      eight patients (82%) had disease recurrence and 32 (45%) had died at study
      census. Of the 71 patients, 19, 29, and 23 patients had a CRS of 1, 2, and 3,
      respectively. On univariate analysis, the CRS significantly predicted PFS (hazard
      ratio [HR], 3.77; 95% confidence interval [CI], 1.83-7.78; P = 0.000) and OS (HR,
      2.81; 95% CI, 1.16-6.79; P = 0.022). In a multivariate model, the CRS was
      significantly associated with PFS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022) but
      not with OS (HR, 2.39; 95% CI, 0.47-3.08; P = 0.079). Patients with CRS of 1 and
      2 combined were twice as likely to progress during the study period compared with
      patients with a CRS of 3 (HR, 2.0; 95% CI, 1.06-3.78; P = 0.032; median PFS, 16
      vs 26 months). No significant association was observed for OS (CRS 1/2 vs 3; HR,
      1.57; 95% CI, 0.68-3.65; P = 0.291). CONCLUSIONS: In this study, the CRS showed
      independent prognostic significance for PFS but not for OS.

PMID- 28441252
TI  - Paget's Disease of the Vulva: A Review of 20 Years' Experience.
AB  - BACKGROUND: Extramammary Paget's disease is a rare condition, and the vulva is a
      common site for it to occur. Despite this, there is a paucity of literature on
      Paget's disease of the vulva (VPD). A Cochrane meta-analysis could not draw any
      conclusions on interventions in VPD. Our aim was to review our practice and
      improve further management of VPD in our center. METHODS: We reviewed all the
      cases presented to Leeds Gynaecological Oncology Centre between 1988 and 2016.
      All cases identified in this interval were followed up until April 2016. All case
      notes and electronic patient data were retrieved to collate the data. RESULTS: We
      identified 18 cases of VPD. The median age at presentation was 76.9 years.
      Primary surgery was used in 18 cases. Eight patients had wide local excision with
      graft reconstruction. Ten women had wide local excision with primary
      reconstruction. Margins were negative in 27% of the excisions. Sixty percent of
      patients with clear surgical margins had a recurrence, and 69% of patients with
      positive margins had a recurrence; there was no statistical difference between
      the 2 groups for recurrence (P > 0.05). Fifty-eight percent of patients who had
      recurrence had coexisting malignancy. Logistic regression showed no correlation
      of recurrence rates due to either age, margin status, or coexisting malignancies.
      CONCLUSIONS: Paget's disease of the vulva is a rare condition. Our experience
      indicates that most cases may be amenable to surgical treatment at first
      presentation. Negative margin status does not reduce the chance of recurrence,
      and hence patients should be under follow-up for life. The benefit of radical
      surgery in the absence of reduced recurrences, based on margin status, is
      questionable. Radiotherapy and imiquimod are options for extensive lesions or
      recurrent settings. Coexisting malignancies are associated with VPD.

PMID- 28441253
TI  - The Impact of an International Network (Gynecologic Cancer InterGroup) for
      Clinical Research on Global Capacity for Gynecologic Cancer Clinical Trials.
AB  - OBJECTIVE: The objective of this study was to demonstrate that the construction
      of the Gynecologic Cancer InterGroup (GCIG) has increased collaboration and
      accrual to high-quality phase 3 trials at a global level. MATERIALS AND METHODS:
      The GCIG is a collaboration of 29 international cooperative clinical trial groups
      committed to conduct of high-quality phase 3 trials among women with gynecologic
      cancer. A complete bibliography of the reported phase 3 trials has been developed
      and is available on the GCIG Web site http://www.gciggroup.com. A "GCIG trial" is
      a trial in which any 2 or more GCIG member groups are formally involved. We
      reviewed the output of the GCIG from 1997 to 2015 with respect to member
      participation and quality of publication (impact factor and citation index). The
      publications are considered in 3 cohorts, 1997 to 2002, 2003 to 2008, and 2009 to
      2014, for the purposes of comparison and progress. A social network map has been
      developed for these publications to identify how the GCIG has increased capacity
      for clinical trials globally. RESULTS: Using a global map, the number of member
      groups in the GCIG has increased in each of the 3 periods. The total annual
      number of publications and citations within the 1997 to 2015 period has increased
      significantly. The average number of citations per publication is demonstrated in
      each of the 3 periods. The steady increase in the number of citations is used as
      a proxy for the impact of the publications. The impact factor of the journal and
      the number of citations are reported for the 10 most highly cited publications.
      Finally, using a social networking methodology, networking has visibly and
      numerically increased in each of the 3 periods. CONCLUSIONS: Evidence supports
      that the construction of the GCIG has increased collaboration and accrual to high
      quality phase 3 trials at a global level among women with gynecologic cancer.

PMID- 28441254
TI  - Gynecologic Oncologist Perspective About ESMO-ESGO-ESTRO Consensus Conference on
      Endometrial Cancer.
AB  - ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer was simultaneously
      published in 3 prestigious journals and is sure to have a huge impact on the
      clinical practice of gynecologic oncology community and other gynecologic cancer
      care providers.It is a tremendous report representative of great effort. Hovewer,
      as practicing gynecologic oncologists, endometrial carcinoma is the most common
      clinical entity encountered in our routine daily practice; as such, we find some
      of the report confusing and object to some of its findings, as detailed in this
      brief report.We also attempted to summarize the differences between the well
      known NCCN guidelines and the ESMO-ESGO-ESTRO Consensus Conference guidelines and
      try to give the point of view of gynecologic oncologic perspective. It is obvious
      that differences in the management of endometrial carcinomas will continue to be
      debated by the scientific community.

PMID- 28441255
TI  - European Society of Gynaecological Oncology Guidelines for the Management of
      Patients With Vulvar Cancer.
AB  - OBJECTIVE: The aim of this study was to develop clinically relevant and evidence
      based guidelines as part of European Society of Gynaecological Oncology's mission
      to improve the quality of care for women with gynecologic cancers across Europe.
      METHODS: The European Society of Gynaecological Oncology Council nominated an
      international development group made of practicing clinicians who provide care to
      patients with vulvar cancer and have demonstrated leadership and interest in the
      management of patients with vulvar cancer (18 experts across Europe). To ensure
      that the statements are evidence based, the current literature identified from a
      systematic search has been reviewed and critically appraised. In the absence of
      any clear scientific evidence, judgment was based on the professional experience
      and consensus of the development group (expert agreement). The guidelines are
      thus based on the best available evidence and expert agreement. Prior to
      publication, the guidelines were reviewed by 181 international reviewers
      including patient representatives independent from the development group.
      RESULTS: The guidelines cover diagnosis and referral, preoperative
      investigations, surgical management (local treatment, groin treatment including
      sentinel lymph node procedure, reconstructive surgery), radiation therapy,
      chemoradiation, systemic treatment, treatment of recurrent disease (vulvar
      recurrence, groin recurrence, distant metastases), and follow-up.

PMID- 28441256
TI  - Interventions to improve adherence of antihypertensive medication in African
      Americans.

PMID- 28441257
TI  - Should elevated blood pressure be lowered in the acute phase of ischaemic stroke?

PMID- 28441258
TI  - Potential of folate supplementation to reduce mortality in hypertensive patients.

PMID- 28441259
TI  - Arterial stiffening by blood pressure increase.

PMID- 28441260
TI  - Reply.

PMID- 28441261
TI  - Blood pressure control in hypertensive patients with chronic kidney disease.

PMID- 28441262
TI  - Reply.

PMID- 28441263
TI  - Endothelin-1-induced endothelial mesenchimal transition via endothelin type B
      receptor stimulation: implication for chronic kidney disease.

PMID- 28441265
TI  - Novel Risk Assessment Tool for Immunoglobulin Resistance in Kawasaki Disease:
      Application Using a Random Forest Classifier.
AB  - BACKGROUND: Resistance to intravenous immunoglobulin (IVIG) therapy is a risk
      factor for coronary lesions in patients with Kawasaki disease (KD). Risk-adjusted
      initial therapy may improve coronary outcome in KD, but identification of high
      risk patients remains a challenge. This study aimed to develop a new risk
      assessment tool for IVIG resistance using advanced statistical techniques.
      METHODS: Data were retrospectively collected from KD patients receiving IVIG
      therapy, including demographic characteristics, signs and symptoms of KD and
      laboratory results. A random forest (RF) classifier, a tree-based machine
      learning technique, was applied to these data. The correlation between each
      variable and risk of IVIG resistance was estimated. RESULTS: Data were obtained
      from 767 patients with KD, including 170 (22.1%) who were refractory to initial
      IVIG therapy. The predictive tool based on the RF algorithm had an area under the
      receiver operating characteristic curve of 0.916, a sensitivity of 79.7% and a
      specificity of 87.3%. Its misclassification rate in the general patient
      population was estimated to be 15.5%. RF also identified markers related to IVIG
      resistance such as abnormal liver markers and percentage neutrophils, displaying
      relationships between these markers and predicted risk. CONCLUSIONS: The RF
      classifier reliably identified KD patients at high risk for IVIG resistance,
      presenting clinical markers relevant to treatment failure. Evaluation in other
      patient populations is required to determine whether this risk assessment tool
      relying on RF has clinical value.

PMID- 28441266
TI  - Safety of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in Children:
      An Open-label, Randomized, Active-controlled, Phase 3 Study.
AB  - BACKGROUND: Japanese encephalitis remains a serious health concern in Asian
      countries and has sporadically affected pediatric travelers. In the present
      study, we monitored the safety profile of the Japanese encephalitis virus vaccine
      IXIARO (Valneva Austria GmbH, Vienna, Austria) in a pediatric population.
      METHODS: We randomized 1869 children between 2 months and 17 years of age in an
      age-stratified manner to vaccination with IXIARO or one of the control vaccines,
      Prevnar (formerly Wyeth Pharmaceuticals Inc., now Pfizer Inc., Kent, United
      Kingdom) and HAVRIX 720 (GlaxoSmithKline Biologicals, Rixensart, Belgium).
      Adverse events (AEs) (unsolicited and solicited local and systemic AEs), serious
      AEs and medically attended AEs were assessed up to day 56 and month 7 after the
      first dose. RESULTS: Incidences of AEs, serious AEs or medically attended AEs did
      not differ significantly between the groups in any age stratum. AEs were most
      frequent in children <1 year of age and decreased with age. AEs of special
      interest, predefined as AEs associated with potential hypersensitivity/allergy or
      neurologic disorders up to day 56, were reported in 4.6% (IXIARO) versus 6.3%
      (Prevnar) in the >=2 months to <1 year age group and 3.4% (IXIARO) versus 3.3%
      (HAVRIX) in the >=1 to <18 years age group. Fever, the most frequent systemic
      reaction in 23.7% of infants to 3.8% of adolescents, decreased with age and did
      not differ between groups. CONCLUSIONS: The safety profile of IXIARO was
      comparable to the control vaccines in terms of overall AE rates, serious AEs and
      medically attended AEs.

PMID- 28441268
TI  - Lack of efficacy of infliximab in the treatment of primary sclerosing cholangitis
      in inflammatory bowel diseases in childhood.

PMID- 28441264
TI  - CD19 Isoforms Enabling Resistance to CART-19 Immunotherapy Are Expressed in B-ALL
      Patients at Initial Diagnosis.
AB  - B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer and
      the prognosis of children with relapsed or therapy refractory disease remains a
      challenge. Treatment with chimeric antigen receptor-modified T cells targeting
      the CD19 antigen (CART-19 therapy) has been presented as a promising approach
      toward improving the outcome of relapsed or refractory disease. However, 10%-20%
      of the patients suffer another relapse. Epitope-loss under therapy pressure has
      been suggested as a mechanism of tumor cells to escape the recognition from CART
      19 therapy. In this work, we analyzed the expression of CD19 isoforms in a cohort
      of 14 children with CD19 B-ALL and 6 nonleukemia donors. We showed that an
      alternatively spliced CD19 mRNA isoform lacking exon 2, and therefore the CART-19
      epitope, but not isoforms lacking the transmembrane and cytosolic domains are
      expressed in leukemic blasts at diagnosis in children and in the bone marrow of
      nonleukemia donors. Furthermore, we clarified the sequence of a further isoform
      lacking the epitope recognized by CART-19 therapy and disclosed the presence of
      new isoforms. In comparison with the children, we showed that alternatively
      spliced CD19 mRNA isoforms affecting exon 2 are also expressed in 6 adult
      patients with CD19 B-ALL. On top of that, one of the adults expressed an isoform
      lacking the CD19 transmembrane and cytosolic domains. In conclusion, we proved
      that some of the CD19 isoforms contributing to CART-19 escape already preexist at
      diagnosis and could evolve as a dominant clone during CART-19 therapy suggesting
      the application of combined treatment approaches.

PMID- 28441270
TI  - Improving quality through clinical registries in urology.
AB  - PURPOSE OF REVIEW: In this review, we highlight the use of clinical registries
      for quality improvement and research purposes in urology. We focus on national
      and regional clinical database registries, such as the National Surgical Quality
      Improvement Programme, the Cancer of the Prostate Strategic Urologic Research
      Endeavor, the Michigan Urological Surgery Improvement collaborative and the
      American Urological Association Quality Registry programme. RECENT FINDINGS: It
      is widely known that claims-based and institutional databases are limited in
      their capacity to provide granular, real-time data for quality improvement
      purposes. As a result, clinical registries have emerged as an attractive
      alternative given their ability to capture large amounts of data across networks
      of health records. Another added benefit of Federally Qualified Clinical Data
      Registries (QCDRs) is the ability to meet emerging Medicare quality reporting
      standards, such as Physician Quality Reporting System and Meaningful Use. Despite
      the enthusiasm for QCDRs in the field of urology, however, myriad challenges
      remain in their implementation and widespread adoption including integration of
      existing health-information technology infrastructure, the accurate measurement
      of quality measures and the availability of clinically relevant quality measures
      in subspecialty practices. SUMMARY: Quality measurement and improvement have
      become important aspects of modern clinical practice. Advances in health
      information technology have ushered in new tools, such as clinical registries,
      which simultaneously improve the quality of scientific research and clinical care
      while assisting eligible professionals in meeting federally mandated reporting
      requirements.

PMID- 28441271
TI  - Alternative payment models and urology.
AB  - PURPOSE OF REVIEW: The Medicare Access and CHIP Reauthorization Act (MACRA) is a
      historic bill that was recently passed that establishes how quality measurement
      and practice patterns will affect physician reimbursement. Alternative payment
      models (APMs) are an essential component of MACRA and Medicare's vision of paying
      for high-value care. This review describes APMs in the context of MACRA and their
      impact on urology. RECENT FINDINGS: The majority of urologists will be affected
      by MACRA. Both APMs and bundled payments are considered APMs under MACRA.
      Although most urologists do not currently participate in Accountable Care
      Organizations (ACOs) and Bundled Payments, both models are considered APMs under
      MACRA and are likely going to gain increasing attention in the coming years.
      SUMMARY: APMs will likely become more relevant to urologists' practices in the
      future, as both the Centers for Medicare and Medicaid Services and private payers
      are transitioning away from fee-for-service towards value-based payment.

PMID- 28441272
TI  - Treating Smoking in Adults With Co-occurring Acute Psychiatric and Addictive
      Disorders.
AB  - OBJECTIVES: Tobacco use is undertreated in individuals with psychiatric and
      substance use disorders (SUDs), with concerns that quitting smoking may
      compromise recovery. We evaluated outcomes of a tobacco intervention among
      psychiatric patients with co-occurring SUDs. METHODS: Data from 2 randomized
      tobacco treatment trials conducted in inpatient psychiatry were combined;
      analyses focused on the subsample with co-occurring SUDs (n = 216). Usual care
      provided brief advice to quit and nicotine replacement therapy during the smoke
      free hospitalization. The intervention, initiated during hospitalization and
      continued 6 months after hospitalization, was tailored to readiness to quit
      smoking, and added a computer-assisted intervention at baseline, and 3 and 6
      months; brief counseling; and 10 weeks of nicotine replacement therapy after
      hospitalization. Outcomes were 7-day point prevalence abstinence from 3 to 12
      months and past 30-day reports of alcohol and illicit drug use. RESULTS: The
      sample consisted of 34% women, among which 36% were Caucasian, averaging 19
      cigarettes/d prehospitalization; the groups were comparable at baseline. At 12
      months, 22% of the intervention versus 11% of usual care participants were
      tobacco-abstinent (risk ratio 2.01, P = 0.03). Past 30-day abstinence from
      alcohol/drugs did not differ by group (22%); however, successful quitters were
      less likely than continued smokers to report past 30-day cannabis (18% vs 42%)
      and alcohol (22% vs 58%) use (P < 0.05), with no difference in other drug use.
      CONCLUSIONS: Tobacco treatment in psychiatric patients with co-occurring SUDs was
      effective and did not adversely impact recovery. Quitting smoking was associated
      with abstinence from alcohol and cannabis at follow-up. The findings support
      addressing tobacco in conjunction with alcohol and other drugs in psychiatric
      treatment.

PMID- 28441273
TI  - Case Report of Physiologic Phenibut Dependence Treated With a Phenobarbital Taper
      in a Patient Being Treated With Buprenorphine.
AB  - : This case report describes the development of dependence to phenibut, a gamma
      aminobutyric acid-receptor type B agonist, in a patient concurrently being
      treated with buprenorphine. The patient experienced withdrawal symptoms which
      were successfully treated with a phenobarbital taper based on a protocol to treat
      sedative use disorder. This case report provided an example of the development of
      a phenibut use disorder and also brought up a public health question of whether
      phenibut should therefore be officially classified and monitored.

PMID- 28441274
TI  - "Meth Mouth": An Interdisciplinary Review of a Dental and Psychiatric Condition.
AB  - OBJECTIVE: Chronic methamphetamine (MA) users experience many dental problems, a
      condition characterized as "meth mouth." These devastating effects on dentition
      is the main reason why many seek professional help. Here, we discuss the effects
      of MA on oral health and advocate for improved collaboration between dentists and
      mental health providers. We also introduce a dental evaluation tool with the goal
      of improving the quality of care for this often-marginalized patient population.
      METHODS: A Medline literature search (1985-2016) was conducted with keywords
      "meth mouth," "methamphetamine AND oral health"; "methamphetamine AND dental";
      "methamphetamine AND dentist." Results were supplemented by references gleaned
      from recent reviews, credible online sources, and citations of search returns.
      RESULTS: MA predisposes users to tooth decay. They are also more likely to have
      missing dentition with a linear relationship correlating the number of years of
      use. A constellation of dental symptoms resulting from chronic MA use has been
      described in literature: gingival inflammation, excessive tooth wear, decreased
      salivary output, and severe dental caries. With continued use, mucosal lesions
      may appear on the lips and the gingival tissue may recede. MA can trigger
      bruxism, resulting in severe wear patterns and even cracked teeth. CONCLUSIONS:
      Users of MA have many unmet medical and mental health needs. An interdisciplinary
      approach between dentists and mental health providers can improve outcomes. The
      dental evaluation tool described here can improve the bidirectional collaboration
      between mental health and dentistry. Dental professionals are in a unique
      position to identify users and can facilitate referral to substance abuse
      treatment. Likewise, mental health providers can identify, assess severity, and
      prompt users for medical and dental attention.

PMID- 28441275
TI  - Peer Reviewers Are Our Strength.

PMID- 28441276
TI  - AUGS Consensus Statement: Association of Anticholinergic Medication Use and
      Cognition in Women With Overactive Bladder.
AB  - Overactive bladder affects a significant portion of the overall population and
      has substantial impact on daily activities and quality-of-life. When considering
      treatment, behavioral therapies should be instituted first, followed by medical
      therapies. Anticholinergic medications and beta-3 agonists are often used as
      initial pharmacologic therapy, but caution should be taken in prescribing
      anticholinergic medications in frail or cognitively impaired patients. Recently,
      concerns have developed regarding anticholinergic medications and the associated
      risk of cognitive impairment, dementia, and Alzheimer disease in the general
      population. Given the available evidence, which has shown significant
      associations between anticholinergic medication use and increased risk of
      cognitive impairment and dementia, providers should counsel on the associated
      risks, prescribe the lowest effective dose, and consider alternative medications
      in patients at risk.

PMID- 28441277
TI  - Symptomatic Epidermoid Cyst Presenting as a Paravaginal Mass.
AB  - BACKGROUND: Ischioanal fossa epidermoid cysts are uncommon masses of epithelial
      origin and are believed to be either congenital or the result of trauma. Surgical
      excision is preferred as opposed to incision and drainage because these masses
      may enlarge, recur, become infected, or undergo malignant transformation. CASE:
      This report describes a case of a 62-year-old woman who presented for evaluation
      of vaginal and perineal discomfort and fullness. Physical examination and
      computed tomography scan revealed a 7.1-cm cystic mass in the left ischioanal
      space. Transgluteal surgical excision was performed and pathology revealed an
      epidermoid cyst. The patient recovered with symptomatic improvement. CONCLUSIONS:
      This report demonstrates a rare case of ischioanal fossa epidermoid cyst. In
      cases of rectal masses, cystic lesions should be considered. Thorough physical
      examination, imaging studies, and proper surgical management of these masses can
      improve patient symptomatology, prevent recurrence, and also decrease the risk of
      malignant transformation.

PMID- 28441278
TI  - The Utility of Routine Postoperative Radiographs After Pinning of Pediatric
      Supracondylar Humerus Fractures.
AB  - BACKGROUND: The purpose of this study was to determine the frequency with which
      postoperative radiographs resulted in a change in management following closed
      reduction and percutaneous pinning of displaced pediatric supracondylar humerus
      fractures. We hypothesize that only the initial postoperative radiograph will
      lead to changes in management of operative supracondylar humerus fractures.
      METHODS: A retrospective review was performed at 2 level I pediatric trauma
      centers. Inclusion criteria were patients below 18 years of age who sustained
      supracondylar humerus fractures (Gartland type II, III, IV) who were operatively
      treated from 2008 to 2013 with adequate radiographic follow-up. Patients with
      flexion type, intra-articular, transphyseal, and open fractures were excluded
      from the study. Routine radiographs were taken at initial follow-up (1 wk
      postoperatively) and at pin removal (3 to 4 wk postoperatively). RESULTS: The
      final analysis included 572 patients. Initial postoperative radiographs changed
      treatment in 9 patients (1.6%), including revision surgeries, 2 pin adjustments,
      and 2 early pin removals. At the time of pin removal, 20 (3.5%) patients required
      further immobilization. There were no changes to the initial plan for continued
      nonoperative treatment at final follow-up (6 to 8 wk postoperatively).
      CONCLUSIONS: In this large retrospective series of patients treated with closed
      reduction and percutaneous pinning of displaced supracondylar humerus fractures,
      radiographs at 3 weeks do not reveal a need to return to the operating room or
      other significant pathology. These findings suggest that radiographs should be
      obtained within 7 to 10 days postoperatively for type III fractures and may only
      need to be repeated if the clinical situation warrants it, such as severe
      fracture pattern, persistent pain, or clinical deformity. LEVEL OF EVIDENCE:
      Level IV-case series.

PMID- 28441279
TI  - Congenital Etiology is an Independent Risk Factor for Complications in
      Adolescents Undergoing Corrective Scoliosis Surgery: Comparison of In-hospital
      Comorbidities Using Nationwide KID's Inpatient Database.
AB  - BACKGROUND: Congenital scoliosis (CS) is associated with more rigid, complex
      deformities relative to adolescent idiopathic scoliosis (AIS) which theoretically
      increases surgical complications. Despite extensive literature studying AIS
      patients, few studies have been performed on CS patients. The purpose of this
      study was to evaluate complications associated with spinal fusions for CS and
      AIS. METHODS: A retrospective review of the Kid's Inpatient Database (KID) years
      2000 to 2009 was performed. Inclusion: patients under 20 years with ICD-9
      diagnosis codes for idiopathic scoliosis (IS-without concomitant congenital
      anomalies) and CS, undergoing spinal fusion from the KID years 2000 to 2009. Two
      analyses were performed according to age below 10 years and 10 years and above.
      Univariate analysis described differences in demographics, comorbidities,
      intraoperative complications, and clinical values between groups. Binary logistic
      regression controlling for age, sex, race, and invasiveness predicted
      complications risk in CS (odds ratios; 95% confidence interval). RESULTS: In
      total, 25,131 patients included (IS, n=22443; CS, n=2688). For patients under age
      10, CS patients underwent 1 level shorter fusions (P<0.001), had fewer
      comorbidities (P<0.001), and sustained similar complication incidence. In the 10
      and over age analysis, CS patients similarly had shorter fusions, but greater
      comorbidities, and significantly more complications (odds ratio, 1.6; confidence
      interval, 1.4-1.8). CONCLUSIONS: CS patients have higher in-hospital complication
      rates. With more comorbidities, these patients have increased risk of sustaining
      procedure-related complications such as shock, infection, and Adult Respiratory
      Distress Syndrome. These data help to counsel patients and their families before
      spinal fusion. LEVEL OF EVIDENCE: Level III-retrospective review of a
      prospectively collected database.

PMID- 28441280
TI  - The Clinical Utility of Flexion-Extension Cervical Spine MRI in 22q11.2 Deletion
      Syndrome.
AB  - BACKGROUND: Our goal is to correlate the findings on flexion and extension
      radiographs with dynamic magnetic resonance imaging (MRI), and the clinical
      history, in a nonrandomly selected cohort of patients with 22q11.2 deletion
      syndrome (22q). METHODS: All patients with the 22q who had a dynamic MRI from
      January 2004 to March 2015 were included. We analyzed multiple radiographic
      measurements on both the dynamic plain films and the MRIs, and correlated these
      findings with a review of each patient's medical record. RESULTS: Multiple
      congenital anomalies were identified as noted in previous studies, and 61% of the
      patients had a failure of fusion of the anterior (n=2, 9%), posterior (n=2, 9%),
      or anterior and posterior arches (n=10, 43%). Quantitative measurements were
      impossible to report with certainty because of the upper cervical anomalies, and
      no cases of instability were identified using a qualitative assessment. We
      identified spinal cord encroachment (30%) and impingement (18%); however, none of
      the patients had any signal change in their spinal cord. None of these findings
      could be definitively correlated with any clinical symptoms. A single patient was
      diagnosed with a Chiari I malformation, while another had cerebellar ectopia.
      CONCLUSIONS: Although the upper cervical anomalies are extremely common in 22q,
      we did not identify cases of instability on dynamic plain radiographs and MRI.
      Although our findings do not support routine screening with flexion and extension
      MRI, this study may be required in patients with neurological symptoms and/or
      findings or abnormalities on dynamic plain radiographs. LEVEL OF EVIDENCE: Level
      III.

PMID- 28441281
TI  - Incarcerated Medial Epicondyle Fractures With Elbow Dislocation: Risk Factors
      Associated With Morbidity.
AB  - BACKGROUND: Incarcerated medial epicondyle fractures in association with elbow
      trauma are rare and an absolute indication for intervention. Because of the
      infrequent nature, outcomes following this injury are not well documented. We
      studied a large cohort of these injuries to determine factors associated with
      functional outcomes. It was hypothesized that a greater duration between initial
      presentation and time of surgery would lead to poorer outcomes. METHODS: A total
      of 32 patients aged 18 and under who underwent surgical treatment for an
      incarcerated medical epicondyle fracture at a level-1 pediatric trauma center
      from 2003 to 2015 were identified. All patients had a confirmed diagnosis of an
      incarcerated medial epicondyle at surgery. Medical records and radiographs were
      reviewed to determine the patient demographics, mechanism of injury, preoperative
      neurological symptoms, time of primary presentation, time of elbow reduction, and
      time to surgical intervention. Postoperative outcomes, including pain, range of
      motion, and ulnar nerve symptoms, were also collected. The Roberts outcome score
      was determined for each subject. RESULTS: A radiographically confirmed elbow
      dislocation was identified in 25 subjects. The mean age at injury was 13.2 years
      (range, 7.3 to 17.8 y). Initial presentation was at a referring institution in 30
      patients (94%). First closed reduction attempt of the ulnohumeral joint occurred
      in the emergency room in 24 subjects (75%); of these 7 subjects (22%) had a first
      reduction attempted in the emergency room at our institution, 2 patients
      experienced first elbow reduction during surgical intervention. The median time
      from first presentation to surgery was 21.9 hours (interquartile range, 15 to
      40). Fourteen subjects displayed preoperative ulnar nerve symptoms. Of these, 9
      subsequently reported postoperative ulnar nerve symptoms. There was no effect of
      time to surgical intervention on the Roberts outcome scores at follow-up, nerve
      symptoms, symptomatic hardware, or need for second surgery to remove hardware.
      There were 16 subjects with excellent outcomes, 13 with good outcomes, 3 with
      fair outcomes, and 0 with poor outcomes (based on the Roberts criteria).
      CONCLUSIONS: Incarcerated medial epicondyle fractures are commonly associated
      with ulnar nerve symptoms; however, they are not associated with a significant
      rate of other complications. There was no increased risk of complications in
      subjects who had a longer duration between initial presentation and surgery. This
      suggests that, while the presence of an incarcerated medial epicondyle fracture
      is certainly an indication for timely operative intervention; the injury in
      isolation does not need to be considered emergent. Other factors including
      neurovascular status and ability to achieve joint reduction may still necessitate
      emergency operative care. LEVEL OF EVIDENCE: Level IV-therapeutic study, case
      series.

PMID- 28441282
TI  - Magnetic Field Reference Levels for Arbitrary Periodic Waveforms for Prevention
      of Peripheral Nerve Stimulation.
AB  - Guidelines for prevention of peripheral nerve stimulation from exposure to low
      frequency magnetic fields have been developed by standard-setting bodies.
      Exposure limits or reference levels (RLs) are typically set in terms of the
      maximum root-mean-square amplitude of a sinusoidal waveform; however,
      environmental flux densities are often periodic, non-sinusoidal waveforms. This
      work presents a procedure for deriving RLs for any generalized periodic waveform
      using the empirical nerve-stimulation threshold data obtained from human
      volunteer MRI experiments. For this purpose, the "Law of Electrostimulation"
      (LOE), which sets forth conditions of a waveform necessary to trigger the action
      potential required to depolarize cell membranes, is applied to various waveforms.
      The results of the LOE analysis are waveform-specific, amplitude thresholds of
      stimulation that are found in terms of the empirically-derived rheobase threshold
      time-rate-of-change flux density and chronaxie from trapezoidal pulse MRI
      experiments. The thresholds are converted to amplitude RLs in two asymptotic
      frequency regimes as per the usual practice in standard setting. The resulting
      RLs have the same frequency dependence as in existing standards (i.e., inverse
      frequency below a transition frequency and flat above). It is shown that the
      transition frequency is dependent only on the shape of the waveform. Both
      sinusoidal and non-sinusoidal waveforms have identical peak-to-peak amplitude RLs
      above their respective transition frequencies. Below these frequencies, all peak
      to-peak amplitude RLs have the same functional dependence on frequency when the
      frequency is normalized to the waveform-specific transition frequency. This
      results in simple criteria for testing the amplitude of any arbitrary periodic
      waveform against potential for stimulation. These criteria are compared to
      guidance given for non-sinusoidal waveforms in the ICNIRP 1 Hz-100 kHz exposure
      standard.

PMID- 28441283
TI  - Early Intake of Radiocesium by Residents Living Near the Tepco Fukushima Dai-ichi
      Nuclear Power Plant After the Accident. Part 2: Relationship Between Internal
      Dose and Evacuation Behavior in Individuals.
AB  - The Tokyo Electric Power Company's Fukushima Dai-ichi Nuclear Power Plant (FDNPP)
      accident exposed members of the public to radiation. This study analyses the
      relation between personal behavior data obtained from 112 out of 174 subjects who
      underwent whole-body measurements by the National Institute of Radiological
      Sciences (NIRS) during the period from 27 June to 28 July 2011 and their
      committed effective doses (CEDs) from Cs and Cs. The whereabouts of the 112
      persons living in municipalities near the FDNPP (mainly, Namie town) on several
      days in March 2011 are graphed on maps. It was confirmed that most subjects
      started evacuation promptly and had left the 20-km-radius of the FDNPP by the end
      of 12 March. The individual CEDs were poorly correlated with the person's
      distances from the FDNPP at any day in March. Meanwhile, the percentage of
      persons remaining within the 20-km radius of the FDNPP was 100% at 16:00 on 12
      March and 42.9% at 0:00 on 15 March for those with CEDs > 0.1 mSv, whereas the
      corresponding values were much lower for those with CEDs <= 0.1 mSv. This
      suggests that the time of evacuation would be one of the crucial factors for the
      early intake; however, more personal behavior data are needed to be analyzed to
      clarify the relevance to the individual internal dose.

PMID- 28441284
TI  - Comparison of Homogeneous and Particulate Lung Dose Rates For Small Mammals.
AB  - Small, highly radioactive fragments of material incorporated into metallic
      matrices are commonly found at nuclear weapons test and accident sites and can be
      inhaled by wildlife. Inhaled particles often partition heterogeneously in the
      lungs, with aggregation occurring in the periphery of the lung, and are
      tenaciously retained. However, dose rates are typically calculated as if the
      material were homogeneously distributed throughout the entire organ. Here the
      authors quantify the variation in dose rates for alpha-, beta-, and gamma
      emitting radionuclides with particle sizes from 0.01-150 MUm (alpha) and 1-150
      MUm (beta, gamma) and considering three averaging volumes-the entire lung (64
      cm), a 10-cm volume of tissue, and a 1-cm volume of tissue. Dose rates from beta
      emitting particles (e.g., Sr) were approximately one order of magnitude higher
      than those from gamma-emitting radionuclides (e.g., Cs). Self-shielding within
      the particle, which reduces the dose rate to the surrounding tissue, was
      negligible for gammas and minor for betas. For alpha-emitting particles (e.g.,
      Pu), self-shielding in larger particles is substantial, with >90% of emissions
      captured within particles of +20 MUm diameter; but for smaller sizes of the
      respirable range of 0.01 to 5 MUm, an average of 85% of the energy escapes the
      particle and is deposited in the surrounding tissues. These data provide more
      detail on respirable particles, which may remain lodged deep in the lung where
      they represent a considerable contribution to long-term lung dose rates. For
      practical dose rate calculation purposes, a graph of particle size vs. dose rates
      for plutonium-containing hot particles is provided. This study demonstrates one
      possible approach to dose assessments for biota in environments contaminated by
      radioactive particles, which may prove useful for those engaged in environmental
      radioprotection.

PMID- 28441285
TI  - Induced Radioactivity in Lead Shielding at the National Synchrotron Light Source.
AB  - The National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory
      was shut down in September 2014. Lead bricks used as radiological shadow
      shielding within the accelerator were exposed to stray radiation fields during
      normal operations. The FLUKA code, a fully integrated Monte Carlo simulation
      package for the interaction and transport of particles and nuclei in matter, was
      used to estimate induced radioactivity in this shielding and stainless steel beam
      pipe from known beam losses. The FLUKA output was processed using MICROSHIELD(r)
      to estimate on-contact exposure rates with individually exposed bricks to help
      design and optimize the radiological survey process. This entire process can be
      modeled using FLUKA, but use of MICROSHIELD(r) as a secondary method was chosen
      because of the project's resource constraints. Due to the compressed schedule and
      lack of shielding configuration data, simple FLUKA models were developed. FLUKA
      activity estimates for stainless steel were compared with sampling data to
      validate results, which show that simple FLUKA models and irradiation geometries
      can be used to predict radioactivity inventories accurately in exposed materials.
      During decommissioning 0.1% of the lead bricks were found to have measurable
      levels of induced radioactivity. Post-processing with MICROSHIELD(r) provides an
      acceptable secondary method of estimating residual exposure rates.

PMID- 28441286
TI  - Behavior of Americium in Simulated Wounds in Nonhuman Primates.
AB  - An americium solution injected intramuscularly into several nonhuman primates
      (NHPs) was found to behave differently than predicted by the wound models
      described in the NCRP Report 156. This was because the injection was made along
      with a citrate solution, which is known to be more soluble than chlorides,
      oxides, or nitrates on which the NCRP Report was based. A multi-exponential wound
      model specific to the injected americium solution was developed based on the
      retention in the intramuscular sites. The model was coupled with the americium
      systemic model to interpret the urinary excretion data and assess the intake, and
      it was determined that the models were adequate to predict early urinary
      excretion in most cases but unable to predict late urinary excretion. This was
      attributed to the differences in the systemic handling of americium between
      humans and nonhuman primates. Information on the type of wounds, solubility,
      particle size, mass, chemical form, etc., should always be considered when
      performing wound dosimetry.

PMID- 28441287
TI  - Lessons Learned in Protection of the Public for the Accident at the Fukushima
      Daiichi Nuclear Power Plant.
AB  - What insights can the accident at the Fukushima Daiichi nuclear power plant
      provide in the reality of decision making on actions to protect the public during
      a severe reactor and spent fuel pool emergency? In order to answer this question,
      and with the goal of limiting the consequences of any future emergencies at a
      nuclear power plant due to severe conditions, this paper presents the main
      actions taken in response to the emergency in the form of a timeline. The focus
      of this paper is those insights concerning the progression of an accident due to
      severe conditions at a light water reactor nuclear power plant that must be
      understood in order to protect the public.

PMID- 28441288
TI  - Investigation of Optically Stimulated Luminescence and Signal Fading Properties
      of Several Materials.
AB  - Optically stimulated luminescence (OSL) dosimetry involves the illumination of an
      irradiated sample on an appropriate material to produce a stimulated emission of
      light, whose intensity is indicative of the radiation dose. This technique is
      currently used for personnel dosimetry, environmental dosimetry, and geological
      dating applications. While a great deal of published research focusing on alpha
      Al2O3:C and natural materials used for geological dating exist, relatively little
      is known about the OSL properties of thermoluminescent (TL) materials. This paper
      reports the results of an experiment conducted to characterize the OSL behavior
      of KBr, CaSO4:Tm, CaSO4:Dy, CaSO4:Dy+P, LiF:Mg,Cu,Na,Si, and LiF:Mg,Cu,Si. The
      OSL signal responses to seven excitation wavelengths from 625 nm to 455 nm for
      each material were measured at 12 time periods post-irradiation from 6 h to 120
      d. The magnitude and fading characteristics of the OSL response of each material
      were then analyzed. The data demonstrated that significant OSL responses exist
      for CaSO4:Tm, LiF:Mg,Cu,Na,Si, and LiF:Mg,Cu,Si. In addition, it was found that
      the fading rates of OSL signals depend on the excitation wavelength used to
      elicit the signals and that these fading rates and the corresponding excitation
      wavelengths correlate well with the material's TL behavior. Thus, the various
      fading rates with respect to the excitation wavelengths could be used to obtain
      temporal dose information.

PMID- 28441289
TI  - Radiological/Nuclear Human Monitoring Tabletop Exercise: Recommendations and
      Lessons Identified.
AB  - Health Canada is the lead department for coordinating the federal response to a
      Canadian nuclear emergency event. The framework to manage a radiological
      consequence is outlined in the Federal Nuclear Emergency Plan (FNEP). In 2014, a
      full scale exercise (FSX) was held to test the capacity of the federal government
      to handle a nuclear facility emergency disaster in Canada. The FSX provided a
      means to demonstrate the integration of various departments and agencies in
      response to such an event, and although a number of task teams within FNEP were
      tested, the capacity to monitor humans for exposure post-event was not played out
      fully. To address this, a table top exercise (TTX) was held in 2015 that brought
      together experts from human monitoring groups (HMGs) in partnership with
      Provincial and Municipal emergency response organizations. The TTX took the form
      of a facilitated discussion centered around two types of radiological/nuclear
      (RN) emergency scenarios that commenced post-release. The purpose of the exercise
      was to integrate these communities and identify knowledge gaps in policies and
      concepts of operations pertaining to the human monitoring aspects of RN events
      including biodosimetry, bioassay, portal monitors, whole body counting, and the
      provision of personal dosimetry. It also tested the interoperability between
      first responders/receivers and Federal, Provincial, and Municipal emergency
      response organizations. The end outcome was the identification of clear knowledge
      gaps in existing and newly developed concepts of operation in the human
      population monitoring response to an RN emergency in Canada; these and possible
      recommendations are captured in this report.

PMID- 28441294
TI  - Effects of Myofascial Release in Nonspecific Chronic Low Back Pain: A Randomized
      Clinical Trial.
AB  - STUDY DESIGN: Double-blind, randomized parallel sham-controlled trial with
      concealed allocation and intention-to treat analysis. OBJECTIVE: To investigate
      the effects of an isolate myofascial release (MFR) protocol on pain, disability,
      and fear-avoidance beliefs in patients with chronic low back pain (CLBP). SUMMARY
      OF BACKGROUND DATA: MFR is a form of manual medicine widely used by
      physiotherapists in the management of different musculoskeletal pathologies. Up
      to this moment, no previous studies have reported the effects of an isolated MFR
      treatment in patients with CLBP. METHODS: Fifty-four participants, with
      nonspecific CLBP, were randomized to MFR group (n = 27) receiving four sessions
      of myofascial treatment, each lasting 40 minutes, and to control group (n = 27)
      receiving a sham MFR. Variables studied were pain measured by means Short Form
      McGill Pain Questionnaire (SF-MPQ) and visual analog scale (VAS), disability
      measured with Roland Morris Questionnaire, and fear-avoidance beliefs measured
      with Fear-Avoidance Beliefs Questionnaire. RESULTS: Subjects receiving MFR
      displayed significant improvements in pain (SF-MPQ) (mean difference -7.8; 95%
      confidence interval [CI]: -14.5 to -1.1, P = 0.023) and sensory SF-MPQ subscale
      (mean difference -6.1; 95% CI: -10.8 to -1.5, P = 0.011) compared to the sham
      group, but no differences were found in VAS between groups. Disability and the
      Fear-Avoidance Beliefs Questionnaire score also displayed a significant decrease
      in the MFR group (P < 0.05) as compared to sham MFR. CONCLUSION: MFR therapy
      produced a significant improvement in both pain and disability. Because the
      minimal clinically important differences in pain and disability are, however,
      included in the 95% CI, we cannot know whether this improvement is clinically
      relevant. LEVEL OF EVIDENCE: 2.

PMID- 28441295
TI  - TO THE EDITOR.

PMID- 28441296
TI  - TO THE EDITOR.

PMID- 28441297
TI  - TO THE EDITOR.

PMID- 28441298
TI  - TO THE EDITOR.

PMID- 28441299
TI  - TO THE EDITOR.

PMID- 28441300
TI  - Speech Detection in Noise for Young Bilaterally Implanted Children: Is There
      Evidence of Binaural Benefit Over the Shadowed Ear Alone?
AB  - OBJECTIVES: To measure binaural benefit over the shadowed ear alone for young
      bilateral cochlear implant (CI) users. It was hypothesized that children who
      received bilateral CIs at a young age (<4 years), and had significant bilateral
      experience, would demonstrate lower detection thresholds for speech sounds in
      background noise in the bilateral CI over the unilateral CI condition when the
      added CI was ipsilateral to the noise source. DESIGN: Children receiving
      bilateral CIs at the Eye and Ear Hospital Clinic in Melbourne were invited to
      participate in a wider research project evaluating outcomes; those participating
      in the wider project who were bilaterally implanted by 4 years and were
      approximately 2 years postoperative were included in the present study. For 20
      participants, detection signal to noise ratios (SNRs) were measured for speech
      presented from in front and noise from 90 degrees  in at least 3 of 4
      device/noise conditions, namely left CI/noise right and right CI/noise left, plus
      bilateral CIs/noise right and bilateral CIs/noise left. RESULTS: As some
      participants could only complete testing in 3 conditions within the 1 test block,
      the unilateral versus bilateral comparison was performed for 1 CI (i.e., 1 noise
      direction) for 15 participants and for both CIs (i.e., noise left and noise
      right) for 5 participants. Group analysis indicated no significant difference in
      detection SNR between the unilateral and bilateral CI conditions when adding the
      left CI or right CI (for the overall group) or when adding the first or second CI
      (for the 15 participants with sequential bilateral CIs). Separate analyses
      indicated no significant difference in detection SNR between the unilateral and
      bilateral CI conditions for the majority of individuals; this occurred
      irrespective of whether the analysis indicated that the CI added in the bilateral
      condition was poorer-performing, better-performing, or not significantly
      different compared with the other CI. Four individuals demonstrated a significant
      improvement in the bilateral condition when the CI added in the bilateral
      condition was a better-performing (n = 1), poorer-performing (n = 2), or not
      significantly different CI (n = 1). There was no relationship between the
      detection SNR difference between each CI and the detection SNR difference between
      the unilateral and bilateral conditions. CONCLUSIONS: The hypothesis of a lower
      detection SNR in the bilateral condition was not supported by the group results
      or by the results for the majority of individuals. For the 4 participants who did
      demonstrate benefit over the shadowed ear alone, that benefit cannot be separated
      from the potential benefit gained as a result of the CI added in the bilateral
      condition being the better-performing CI for 1 of the 4. Variation in outcomes
      could not be related to demographic factors for this group, which was relatively
      homogeneous for age at bilateral CI and experience; an older, more experienced
      group may demonstrate greater binaural benefit in these conditions. These results
      can be used during counseling for families regarding postoperative expectations
      for young children, especially in the first 2 years.

PMID- 28441301
TI  - Regenerative Medicine and Stem Cells in Dermatology.
AB  - BACKGROUND: Clinically relevant regenerative medicine is still in its early
      stages of development. Difficulties in regenerating large-scale and complex
      structures, the lack of safety data, and the paucity of clinical trials have
      slowed the process of technological advance. OBJECTIVE: To familiarize the
      clinician with techniques available in the laboratory and experimental approaches
      being tested clinically. In addition, a layout is discussed for how
      dermatologists can lead the way in bringing regenerative medicine to clinical
      reality. METHODS: This article reviews the relevant literature on regenerative
      medicine for dermatological applications and discusses findings and techniques in
      a clinically relevant context. RESULTS: Multiple cell-free and cell-based
      approaches for regenerating dermatologic tissues have been reported in the basic
      science and clinical literature. These are reviewed in the order of complexity.
      CONCLUSION: Incremental steps are needed to apply the principles of regenerative
      medicine to simple medical problems first. Such a stepwise approach would
      commence, for example, with creation of single-function tissues that could fill
      soft-tissue defects and proceed to the development of fully functional skin
      grafts. Likewise, cell-free approaches can build the foundation for the more
      technically demanding cell-based strategies that are likely necessary for
      achieving the ultimate goal of regenerative dermatology.

PMID- 28441302
TI  - Commentary on Striae Distensae.

PMID- 28441303
TI  - Surgical Techniques for Closure of a Scalp Defect After Resection of Skin
      Malignancy.
AB  - BACKGROUND: Surgery for scalp malignancies is aimed at the complete resection and
      a good aesthetic outcome. The goal was to develop an algorithm for scalp
      reconstruction based on the authors' surgical experience. METHODS: This is a
      retrospective analysis of 123 procedures of scalp malignancies in 105 patients.
      Twenty eight procedures were for resection of squamous cell carcinoma, 54 for
      basal cell carcinoma, and 41 for suspected melanomas. RESULTS: Primary closure
      (27 procedures), local flap (LF; 19), split-thickness skin graft (SG; 64),
      rotated LF and SG (9), and free vascularized flaps (4) were used. Complications
      were partial (4) and total (1) necrosis of SG, free-flap atrophy (1), infection
      (2), wound dehiscence (1), and death due to cardiovascular complications (1).
      During follow-up, recurrence occurred in 22 patients (21%) and metastases to
      lymph nodes in 3 (3%). CONCLUSION: Surface area size and the presence of the
      periosteum as well as a bone infiltration are important factors that can guide
      selection of a reconstruction method after resection of scalp malignancy.

PMID- 28441304
TI  - Suggested Injection Zone for Soft Tissue Fillers in the Temple?

PMID- 28441305
TI  - Step-by-Step Technique for Segmental Reconstruction of Reverse Hill-Sachs Lesions
      Using Homologous Osteochondral Allograft.
AB  - Posterior shoulder dislocations are accompanied by high forces and can result in
      an anteromedial humeral head impression fracture called a reverse Hill-Sachs
      lesion. This reverse Hill-Sachs lesion can result in serious complications
      including posttraumatic osteoarthritis, posterior dislocations, osteonecrosis,
      persistent joint stiffness, and loss of shoulder function. Treatment is
      challenging and depends on the amount of bone loss. Several techniques have been
      reported to describe the surgical treatment of lesions larger than 20%. However,
      there is still limited evidence with regard to the optimal procedure. Favorable
      results have been reported by performing segmental reconstruction of the reverse
      Hill-Sachs lesion with bone allograft. Although the procedure of segmental
      reconstruction has been used in several studies, its technique has not yet been
      well described in detail. In this report we propose a step-by-step description of
      the technique how to perform a segmental reconstruction of a reverse Hill-Sachs
      defect.

PMID- 28441306
TI  - Orientation of the Upper-most Instrumented Segment Influences Proximal Junctional
      Disease Following Adult Spinal Deformity Surgery.
AB  - STUDY DESIGN: Retrospective review of a prospective database. OBJECTIVE: The aim
      of this study was to define the role of sagittal orientation of the construct at
      the upper instrumented levels in the development of proximal junctional kyphosis
      (PJK) in adult spinal deformity (ASD) patients. SUMMARY OF BACKGROUND DATA: PJK
      following ASD surgery remains challenging. The final alignment of the upper
      instrumented vertebral segments has been proposed as a risk factor for PJK, but
      has not been fully investigated. METHODS: ASD patients with 2-year follow-up and
      long posterior fusion to the pelvis were analyzed. Radiographic measurements
      included pelvic incidence (PI), lumbar lordosis (LL), pelvic tilt (PT), sagittal
      vertical axis, and two upper-most instrumented vertebra (UIV) parameters: UIV
      slope (UIV vs. horizontal) and inclination of the proximal-end of the construct.
      UIV parameters were secondarily evaluated with regard to the compensatory impact
      of post-PJK increased PT (PREF). A comparison between PJK and non-PJK patients
      was performed, according to the UIV location (upper thoracic [UT] or
      thoracolumbar). RESULTS: A total of 252 patients (mean age, 61.5 years, 83%
      females) were included. PJK incidence was 56% at 2-years. PJK patients had a
      greater change in LL and thoracic kyphosis than non-PJK patients. In the UT
      group, there was no difference in UIV slope for PJK versus non-PJK. However, PJK
      patients had a smaller inclination of the upper instrumented segments versus
      vertical (P < 0.001) and the PREF (P = 0.005). Similarly, in the LT group, PJK
      patients had a posterior inclination versus the vertical (P < 0.001) and the PREF
      (P = 0.041). CONCLUSION: Analysis revealed that a more posterior construct
      inclination was present in patients who developed PJK. These results support
      previous hypotheses suggesting that PJK may develop in response to excessive
      spinal realignment. Proper rod contouring, especially at the proximal end, may
      reduce the risk of PJK. LEVEL OF EVIDENCE: 3.

PMID- 28441307
TI  - 90-day Readmission After Lumbar Spinal Fusion Surgery in New York State Between
      2005 and 2014: A 10-year Analysis of a Statewide Cohort.
AB  - : MINI: We assessed 90-day readmission and evaluated risk factors associated with
      readmission after lumbar spinal fusion surgery in New York State. The overall 90
      day readmission rate was 24.8%. Age, sex, race, insurance, procedure, number of
      operated spinal levels, health service area, and comorbidities are major risk
      factors for 90-day readmission. STUDY DESIGN: Retrospective cohort study.
      OBJECTIVE: The aim of this study was to assess 90-day readmission and evaluate
      risk factors associated with readmission after lumbar fusion in New York State.
      SUMMARY OF BACKGROUND DATA: Readmission is becoming an important metric for
      quality and efficiency of health care. Readmission and its predictors following
      spine surgery are overall poorly understood and limited evidence is available
      specifically in lumbar fusion. METHODS: The New York Statewide Planning and
      Research Cooperative System (SPARCS) was utilized to capture patients undergoing
      lumbar fusion from 2005 to 2014. Temporal trend of 90-day readmission was
      assessed using Cochran-Armitage test. Logistic regression was used to examine
      predictors associated with 90-day readmission. RESULTS: There were 86,869
      patients included in this cohort study. The overall 90-day readmission rate was
      24.8%. On a multivariable analysis model, age (odds ratio [OR] comparing >=75
      versus <35 years: 1.24, 95% confidence interval [CI]: 1.13-1.35), sex (OR female
      to male: 1.19, 95% CI: 1.15-1.23), race (OR African-American to white: 1.60, 95%
      CI: 1.52-1.69), insurance (OR Medicaid to Medicare: 1.42, 95% CI: 1.33-1.53),
      procedure (OR comparing thoracolumbar fusion, combined [International
      Classification of Disease, Ninth Revision, ICD-9: 81.04] to posterior lumbar
      interbody fusion/transforaminal lumbar spinal fusion [ICD-9: 81.08]: 2.10, 95%
      CI: 1.49-2.97), number of operated spinal levels (OR comparing four to eight
      vertebrae to two to three vertebrae: 2.39, 95% CI: 2.07-2.77), health service
      area ([HSA]; OR comparing Finger Lakes to New York-Pennsylvania border: 0.67, 95%
      CI: 0.61-0.73), and comorbidity, i.e., coronary artery disease (OR: 1.26, 95% CI:
      1.19-1.33) were significantly associated with 90-day readmission. Directions of
      the odds ratios for these factors were consistent after stratification by
      procedure type. CONCLUSION: Age, sex, race, insurance, procedure, number of
      operated spinal levels, HSA, and comorbidities are major risk factors for 90-day
      readmission. Our study allows risk calculation to determine high-risk patients
      before undergoing spinal fusion surgery to prevent early readmission, improve
      quality of care, and reduce health care expenditures. LEVEL OF EVIDENCE: 3.

PMID- 28441308
TI  - Factors Associated With the Development of and Revision for Proximal Junctional
      Kyphosis in 440 Consecutive Adult Spinal Deformity Patients.
AB  - : MINI: Proximal junctional kyphosis (PJK) is a common, yet incompletely
      understood, complication of surgery for adult spinal deformity. We analyzed 440
      consecutive adult spinal deformity patients for trends in development of PJK and
      need for revision surgery. pelvic tilt and thoracic kyphosis were predictive for
      developing PJK, while radiographic evidence of proximal junctional failure was
      predictive for proceeding to revision. STUDY DESIGN: Retrospective review of
      prospectively collected data. OBJECTIVE: The aim of this study was to examine
      which radiographic parameters and surgical strategies are most closely associated
      with proximal junctional kyphosis (PJK) after adult spinal deformity (ASD)
      surgery, the need for revision surgery for PJK, and whether these differ based on
      the upper instrumented vertebra (UIV). SUMMARY OF BACKGROUND DATA: Multiple
      parameters are considered when planning correction of ASD. Determining which of
      these factors contribute to the development of and need for revision surgery for
      PJK presents a challenging problem. METHODS: Consecutive patients undergoing long
      fusion to the pelvis with age >18 years, minimum 6-month follow-up, and adequate
      radiographs for analysis in a single institution between 2003 and 2011 were
      included. Along with chart review, measurement of proximal junctional angle
      (PJA), sagittal balance, and pelvic parameters was performed on preoperative,
      postoperative, and latest follow-up radiographs. Postoperative radiographs were
      also examined for signs of PJF. RESULTS: A total of 440 patients with a mean
      follow-up of 34 months met inclusion criteria, 159 of whom developed PJK (36%),
      with 65 requiring revision surgery (41%). Higher preoperative pelvic tilt (PT) (P
      = 0.018) and postoperative thoracic kyphosis (TK) (P <= 0.001) were predictive
      for development of PJK, whereas hooks at UIV were protective (odds ratio [OR]
      0.049). In patients who developed PJK, revision was more frequent in younger
      patients (P = 0.005) with greater postoperative sagittal vertical axis and PJA (P
      = 0.029, P = 0.018). PJF with spondylolisthesis, fracture, or instrumentation
      failure at the UIV had the highest ORs for proceeding to a revision (5.1, 1.6,
      and 2.2, respectively). CONCLUSION: TK and PT are important indicators of overall
      rigidity and reference the ability of the spine to compensate for sagittal plane
      deformity. Special attention should be paid to these characteristics and to the
      choice of proximal instrumentation when attempting to prevent PJK. Prevention of
      radiographically evident PJF may hold the key to reducing the need for revision
      surgery. LEVEL OF EVIDENCE: 3.

PMID- 28441309
TI  - Trends, Complications, and Costs for Hospital Admission and Surgery for Lumbar
      Spinal Stenosis.
AB  - : MINI: Trends in lumbar spinal stenosis surgery are largely unknown outside of
      the United States. This population-based health record linkage study revealed
      that complex fusion surgery had a four-fold increase from 2003-2013 in Australia.
      This surgical procedure increased the risk of complications and resource use
      compared with decompression surgery alone. STUDY DESIGN: Population-based health
      record linkage study. OBJECTIVE: The aim of this study was to determine trends in
      hospital admissions and surgery for lumbar spinal stenosis, as well as
      complications and resource use in Australia. SUMMARY OF BACKGROUND DATA: In the
      United States, rates of decompression surgery have declined, whereas those of
      fusion have increased. It is unclear whether this trend is also happening
      elsewhere. METHODS: We included patients 18 years and older admitted to a
      hospital in New South Wales between 2003 and 2013 who were diagnosed with lumbar
      spinal stenosis. We investigated the rates of hospital admission and surgical
      procedures, as well as hospital costs, length of hospital stay, and
      complications. Surgical procedures were: decompression alone, simple fusion (one
      to two disc levels, single approach), and complex fusion (three or more disc
      levels or a combined posterior and anterior approach). RESULTS: The rates of
      decompression alone increased from 19.0 to 22.1 per 100,000 people. Simple fusion
      rates increased from 1.3 to 2.8 per 100,000 people, whereas complex fusion
      increased from 0.6 to 2.4 per 100,000 people. The odds of major complications for
      complex fusion compared with decompression alone was 4.1 (95% confidence interval
      [CI]: 1.7-10.1), although no significant difference was found for simple fusion
      (odds ratio 2.0, 95% CI: 0.7-6.1). Mean hospital costs with decompression surgery
      were AU $12,168, whereas simple and complex fusion cost AU $30,811 and AU
      $32,350, respectively. CONCLUSION: In Australia, decompression rates for lumbar
      spinal stenosis increased from 2003 to 2013. The fastest increasing surgical
      procedure was complex fusion. This procedure increased the risk of major
      complications and resource, although recent evidence suggest fusion provides no
      additional benefits to the traditional decompression surgery. LEVEL OF EVIDENCE:
      3.

PMID- 28441310
TI  - A Dose-Response Curve for a Gram-Negative Spinal Implant Infection Model in
      Rabbits.
AB  - STUDY DESIGN: A randomized complete block animal spinal implant infection model
      with internal control. OBJECTIVE: The aim of this study was to develop a spinal
      implant animal infection model to simulate postoperative gram-negative wound
      infection. SUMMARY OF BACKGROUND DATA: Implant-associated surgical site
      infections (SSIs) remain a dreaded complication of spinal surgery. Currently,
      over 30% of all spine SSIs are secondary to gram-negative bacteria. Traditional
      animal models have utilized gram-positive inoculums to simulate postoperative
      infection, but there exists no model in the literature for gram-negative
      infection in the setting of spinal instrumentation. METHODS: Five New Zealand
      white female rabbits underwent simulated partial laminectomies and implantation
      of a 5 mm titanium wire adjacent to the spinous processes of vertebra T4, T9, L1,
      and L6 to mimic posterior spinal instrumentation. The second site, T9, was used
      as the sterile internal control sites, while all other sites were challenged with
      varying inoculums of Escherichia coli (EC American Type Culture Collection
      25922): 10, 10, 10, 10, and 10 Colony Forming Units (CFU). The rabbits were
      sacrificed 4 days postoperatively and bacterial loads were assayed from the
      implants and surrounding tissue. RESULTS: No evidence for infection was observed
      in any of the sterile control sites. The lowest inoculum of E. coli (10 CFU) did
      not produce a reliable infection. Inoculation with 10 CFU created a consistent
      soft tissue infection, but inconsistent infection on implants. Inoculation with
      10 CFU was required to consistently produce both soft tissue and implant
      infection. CONCLUSION: Consistent soft tissue and implant infection was produced
      with inoculation of 10 CFU of E. coli. Gram-negative infections represent greater
      than 30% of all spinal SSIs, and this animal model can reliably reproduce such
      infections with spinal instrumentation that can guide future development of anti
      infective therapies. LEVEL OF EVIDENCE: 2.

PMID- 28441311
TI  - Feasibility and Outcome of an Accelerated Recovery Protocol in Asian Adolescent
      Idiopathic Scoliosis Patients.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVE: The aim of this study was to
      determine the feasibility of an accelerated recovery protocol for Asian
      adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion
      (PSF). SUMMARY OF BACKGROUND DATA: There has been successful implementation of an
      accelerated recovery protocol for AIS patients undergoing PSF in the western
      population. No similar studies have been reported in the Asian population.
      METHODS: Seventy-four AIS (65 F, 9 M) patients scheduled for PSF surgery were
      recruited. The accelerated protocol encompasses preoperative regime, preoperative
      day of surgery counseling, intraoperative strategies, an accelerated
      postoperative rehabilitation and pain management regime. All patients were
      operated using a dual attending surgeon strategy. Outcome measures included pain
      scores at five time intervals, length of stay, and detailed recovery milestones.
      Any complications or readmissions during the first 4 months postoperative period
      were recorded. RESULTS: Mean duration of operation was 2.2 +/- 0.3 hours with a
      mean blood loss of 824.3 +/- 418.2 mL. No patients received allogenic blood
      transfusion. The mean length of stay was 3.6 +/- 0.6 days. Surgical wound pain
      score was 6.4 +/- 2.1 at 12 hours, which reduced to 5.0 +/- 2.0 at 60 hours.
      Abdominal pain peaked at 36 hours with pain scores 2.4 +/- 2.9. First liquid
      intake was at 5.2 +/- 7.5 hours, urinary catheter removal at 18.7 +/- 4.8 hours,
      sitting up at 20.6 +/- 9.1 hours, ambulation at 27.2 +/- 0.5 hours, consumption
      of solid food at 32.2 +/- 0.5 hours, first flatus at 39.0 +/- 0.7 hours, and
      first bowel movement at 122.1 +/- 2.0 hours. The complication rate was 1.4% due
      to superficial wound infection with one patient failed to comply with the
      accelerated protocol. CONCLUSION: An accelerated recovery protocol following PSF
      for AIS is feasible without increasing the complication or readmission rates. The
      total length of stay was 3.6 days and this is comparable with the outcome in
      western population. LEVEL OF EVIDENCE: 4.

PMID- 28441313
TI  - Clinical Evidence for Spinal Cord Stimulation for Failed Back Surgery Syndrome
      (FBSS): Systematic Review.
AB  - STUDY DESIGN: A systematic review. OBJECTIVE: A systematic literature review of
      the clinical data from prospective studies was undertaken to assess the efficacy
      of spinal cord stimulation (SCS) in the treatment of failed back surgery syndrome
      (FBSS) in adults. SUMMARY OF BACKGROUND DATA: For patients with unrelenting back
      pain due to mechanical instability of the spine, degenerative disc disease,
      spinal injury, or deformity, spinal surgery is a well-accepted treatment option;
      however, even after surgical intervention, many patients continue to experience
      chronic back pain that can be notoriously difficult to treat. Clinical evidence
      suggests that for patients with FBSS, repeated surgery will not likely offer
      relief. Additionally, evidence suggests long-term use of opioid pain medications
      is not effective in this population, likely presents additional complications,
      and requires strict management. METHODS: A systematic literature review was
      performed using several bibliographic databases, prospective studies in adults
      using SCS for FBSS were included. RESULTS AND CONCLUSION: SCS has been shown to
      be a safe and efficacious treatment for this patient population. Recent
      technological developments in SCS offer even greater pain relief to patients'
      refractory to other treatment options, allowing patients to regain functionality
      and improve their quality of life with significant reductions in pain. LEVEL OF
      EVIDENCE: N/A.

PMID- 28441314
TI  - Radiologic Parameters Can Affect the Preoperative Decision Making of Three-Column
      Spinal Osteotomies in the Treatment of Severe and Stiff Kyphoscoliosis.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To evaluate whether radiologic
      parameters affect spine surgeon's osteotomy choice in patients with severe and
      stiff thoracic kyphoscoliosis. SUMMARY OF BACKGROUND DATA: Three-column
      osteotomies were developed to address severe and stiff kyphoscoliosis. Current
      choice on osteotomies is based on the morphology of kyphosis, global balance, and
      locations of the main curvature; however, quantitative basis for decision making
      is still lacking. METHODS: Sixty patients with severe and stiff thoracic
      kyphoscoliosis who underwent three-column osteotomy in the thoracic spine were
      classified into four groups according to the grade of osteotomy. The radiologic
      parameters including maximum scoliosis, maximum kyphosis, deformity angular ratio
      (DAR; maximum Cobb angle divided by number of vertebrae involved), apical
      vertebral translation, coronal balance, and sagittal balance were measured and
      compared. Correlation analysis between the radiologic parameters and the
      osteotomy grades was conducted. Perioperative and long-term complications were
      reviewed. RESULTS: The overall scoliosis was corrected from a mean preoperative
      Cobb angle of 129.1 degrees  (range, 90-174 degrees ) to 56.4 degrees  (range, 14
      100 degrees ), and overall kyphosis was corrected from 124.3 degrees  (range, 64
      180 degrees ) to 54.3 degrees  (range, 11-95 degrees ). As the osteotomy grades
      increased, the mean preoperative maximum kyphosis increased from 104.5 degrees 
      to 151.8 degrees  and the mean sagittal DAR (S-DAR) increased from 16.4 to 24.9.
      Statistically significant between-group differences were found for preoperative
      maximum kyphosis (P = 0.001), S-DAR (P = 0.045), and total DAR (P = 0.033).
      Significant correlations were observed between the preoperative maximum kyphosis
      and the osteotomy grade (r = 0.454, P < 0.001). The S-DAR significantly
      correlated with the osteotomy grade (r = 0.322, P = 0.012). CONCLUSION: The
      preoperative maximum kyphosis and the S-DAR may affect the surgeon's decision on
      the grade of osteotomies. This may enrich the theoretical basis on preoperative
      planning and help with patient counseling. LEVEL OF EVIDENCE: 4.

PMID- 28441315
TI  - An Overview of Chronic Spinal Pain: Revisiting Diagnostic Categories and
      Exploring an Evolving Role for Neurostimulation.
AB  - STUDY DESIGN: Topic overview. OBJECTIVE: To describe the varied etiologies
      resulting in chronic spinal pain and review the current available evidence for
      treatments. SUMMARY OF BACKGROUND DATA: Chronic pain conditions, especially those
      that affect the axial back and radiate to the extremities, affect a large
      population. This results in pronounced disability and a high socioeconomic
      burden. Our understanding of the underlying mechanisms for chronic pain is
      limited. This prevents a comprehensive diagnostic approach. Evidence from high
      level clinical trials supporting treatments for chronic spinal pain is also
      limited. METHODS: Articles were identified through PubMed searches or already
      known to the author. The literature was reviewed and summarized, indicating the
      strength of evidence available for many treatment modalities. RESULTS: There are
      very few studies published that evaluate behavioral modifications for chronic
      spinal pain and only one long-term study investigating chronic pharmacological
      treatments. The data on the success of spinal surgeries to relieve chronic spinal
      pain suggest an unacceptably high failure rate. The best evidence (Level I)
      currently available suggests that spinal cord stimulation is a safe, effective,
      and durable treatment for chronic spinal pain. Recent clinical data support
      further investigation of new innovations and earlier therapeutic consideration of
      currently employed approaches. CONCLUSION: Currently, physicians are limited in
      the practice of evidence-based medicine regarding chronic spinal pain treatments
      due to both the paucity of data available and an inconsistent diagnostic
      nomenclature. The introduction of new neurostimulation modalities is promising
      but requires better characterization through ongoing prospective clinical
      investigation. LEVEL OF EVIDENCE: 5.

PMID- 28441316
TI  - Hemolysis Following Intraoperative Cell Salvage Replacement in a Scoliosis
      Patient With Sickle Cell Trait: A Case Report.
AB  - : MINI: Intraoperative cell salvage (ICS) is used to reduce blood loss in
      scoliosis spinal fusion. We report one case of hemolysis induced acute renal
      failure following ICS. This is the first reported case of acute renal failure
      associated with hemolysis following ICS in a scoliosis patient with sickle cell
      trait. STUDY DESIGN: Case report. OBJECTIVE: To describe a novel presentation of
      acute renal failure associated with hemolysis after intraoperative cell salvage
      (ICS) in a neuromuscular scoliosis patient with sickle cell trait (SCT). SUMMARY
      OF BACKGROUND DATA: Hemolysis-associated acute renal failure after ICS in
      patients with SCT has not been previously reported. Sickle cell disease is
      regarded as a relative contraindication for ICS due to the risk of red blood cell
      sickling in the hypoxic cell saver reservoir. A previous case series demonstrated
      successful ICS reinfusion after elective caesarean section in two patients with
      SCT. However, a decision to not reinfuse ICS collected blood due to increased
      sickling after blood processing was reported in general surgery. METHODS: A 14
      year-old female with Group I neuromuscular scoliosis underwent a navigated T3
      S1posterior spinal instrumentation fusion. Three hundred milliliters of blood
      collected by ICS was reinfused intraoperatively along with two units of packed
      red blood cells. RESULTS: Postoperatively, the patient had delayed emergence from
      the general anesthetic and gross hematuria was observed in the urinary catheter
      bag. The patient was transferred to the intensive care unit and was treated
      successfully for hemolysis-induced renal failure. CONCLUSION: Given the potential
      seriousness of hemolysis-associated acute renal failure associated with ICS, we
      recommend against the use of ICS in patients with SCT. LEVEL OF EVIDENCE: 5.

PMID- 28441317
TI  - Traumatic Spinal Injuries in Northern Finland.
AB  - STUDY DESIGN: A retrospective epidemiological study. OBJECTIVE: To reveal
      incidence and epidemiological features of traumatic spinal injuries (TSI) in
      Northern Finland. SUMMARY OF BACKGROUND DATA: In Finland the annual incidence of
      traumatic spine fractures requiring inpatient care has been found to be
      27/100,000, while international incidences have varied across the range of 16
      64/100,000. More specific epidemiological data from Finland is not available.
      Internationally, the most common mechanisms of injury are road traffic as well as
      low and high falls. Associated injuries occur in 30% to 55% of cases. METHODS:
      The study sample included patients with traumatic spinal injury admitted to Oulu
      University Hospital (OYS) with injury between the January 1, 2007 and December
      31, 2011. Patient information was collected from the hospital care register,
      including all inpatient and outpatient visits and surgical procedures. Traumatic
      spinal column and spinal cord injuries were identified using International
      Classification of Diseases 10th revision or Nordic Classification of Surgical
      Procedures codes and all patient records were manually reviewed. RESULTS: Nine
      hundred seventy-one patients met the criteria for TSI. The mean annual incidence
      of hospitalized traumatic spinal injuries was 26/100,000 in the whole of Northern
      Finland and 35/100,000 in the OYS main responsibility area. The most frequent
      etiology of TSI was low falls, which accounted for 35.8% of the injuries,
      followed by road traffic and high falls. Lumbar spine was the most common site of
      the fracture. Spinal surgery was performed in 376 (38.7%) cases. Three hundred
      eight patients (31.7%) suffered from associated injuries, 101 (10.4%) had a
      spinal cord injury, and 71 (7.3%) a brain injury. CONCLUSION: Low falls in
      elderly and road traffic injuries in younger age groups were the most common
      etiology of traumatic spinal injuries in Northern Finland and should be given
      more attention in primary prevention. LEVEL OF EVIDENCE: 3.

PMID- 28441318
TI  - Retraction: Yu et al. Low Iron Diet Increases Susceptibility to Noise-Induced
      Hearing Loss in Young Rats. Nutrients 2016, 8, 456.
AB  - The Nutrients Editorial Office has recently been made aware that the figures in
      the title paper [1] are taken from the same micrographs as those of other papers
      by the same authors [...].

PMID- 28441319
TI  - Speyeria (Lepidoptera: Nymphalidae) Conservation.
AB  - Speyeria (Nymphalidae) are a conspicuous component of the North American
      butterfly fauna. There are approximately 16 species and >100 associated
      subspecies (or geographical variants). Speyeria are univoltine, occupy a wide
      range of habitats, overwinter as first instar larvae, and feed only on native
      violets. Speyeria species have become a model group for studies of evolution,
      speciation, and conservation. Several species and subspecies are threatened or
      endangered. The reasons for this vary with the taxa involved, but always involve
      the degradation or loss of quality habitat for larvae and adults. The impacts of
      climate change must be considered among the causes for habitat degradation and in
      the establishment of conservation measures. In addition to increasing the
      available habitat, conservation efforts should consider maintaining habitat in a
      seral "disturbed" successional stage that selectively favors the growth of
      violets and preferred adult nectar sources. A major future challenge will be
      determining the most effective allocation of conservation resources to those
      species and subspecies that have the greatest potential to respond favorably to
      these efforts.

PMID- 28441320
TI  - Hyperbaric Oxygen Therapy is Ineffective as an Adjuvant to Daptomycin with
      Rifampicin Treatment in a Murine Model of Staphylococcus aureus in Implant
      Associated Osteomyelitis.
AB  - Implant-associated infections caused by bacterial biofilms are difficult to
      treat. Surgical intervention is often necessary to cure the patient, as the
      antibiotic recalcitrance of biofilms renders them untreatable with conventional
      antibiotics. Intermittent hyperbaric oxygen treatment (HBOT) has been proposed as
      an adjuvant to conventional antibiotic treatment and it has been speculated that
      combining HBOT with antibiotics could improve treatment outcomes for biofilm
      infections. In this study we addressed whether HBOT could improve treatment
      outcomes of daptomycin and rifampicin combination therapy. The effect of HBOT on
      the treatment outcomes of daptomycin and rifampicin against implant-associated
      osteomyelitis was quantified in a murine model. In total, 80 mice were randomized
      into two groups receiving antibiotics, either alone or in combination with daily
      intermittent HBOT (304 kPa for 60 min) following injection of antibiotics.
      Treatment was initiated 11 days after animals were infected with Staphylococcus
      aureus and treatment duration was 14 days. We found that HBOT did not improve the
      cure rate and did not reduce the bacterial load on the implant surface or in the
      surrounding tissue. Cure rates of daptomycin + rifampicin were 40% in infected
      tibias and 75% for implants while cure rates for HBOT-daptomycin + rifampicin
      were 50% and 85%, respectively, which were not significantly higher (Fisher's
      exact test). While it is encouraging that the combination of daptomycin and
      rifampicin is very effective, our study demonstrates that this efficacy cannot be
      improved by adjuvant HBOT.

PMID- 28441321
TI  - A Cost-Effective Relative Humidity Sensor Based on Side Coupling Induction
      Technology.
AB  - A intensity-modulated optical fiber relative humidity (RH) sensor based on the
      side coupling induction technology (SCIT) is presented and experimentally
      demonstrated. The agarose gel and the twisted macro-bend coupling structure are
      first combined for RH sensing applications. The refractive index (RI) of the
      agarose gel increases with the increase of the RH and is in linear proportion
      from 20 to 80%RH. The side coupling power, which changes directly with the RI of
      the agarose gel, can strip the source noise from the sensor signal and improve
      the signal to noise ratio substantially. The experiment results show that the
      sensitivity of the proposed sensor increases while the bend radius decreases.
      When the bend radius is 8 mm, the sensor has a linear response from 40% to 80% RH
      with the sensitivity of 4.23 nW/% and the limit of detection of 0.70%. A higher
      sensitivity of 12.49 nW/% is achieved when RH raises from 80% to 90% and the
      limit of detection decreases to 0.55%. Furthermore, the proposed sensor is a low
      cost solution, offering advantages of good reversibility, fast response time, and
      compensable temperature dependence.

PMID- 28441322
TI  - Erratum: Kim, K.-P.; Singh, A.K.; Bai, X.; Leprun, L.; Bhunia, A.K. Novel PCR
      Assays Complement Laser Biosensor-Based Method and Facilitate Listeria Species
      Detection from Food. Sensors 2015, 15, 22672-22691.
AB  - The authors wish to correct the oligonucleotide sequence of primer E-LAP-F1 and
      LIS-R1 in Table 1in their paper published in Sensors [1], doi:10.3390/s150922672,
      http://www.mdpi.com/1424-8220/15/9/22672. The following table should be
      used.[...].

PMID- 28441323
TI  - Gold Nanoplates for a Localized Surface Plasmon Resonance-Based Boric Acid
      Sensor.
AB  - Localized surface plasmon resonance (LSPR) properties of metallic nanostructures,
      such as gold, are very sensitive to the dielectric environment of the material,
      which can simply be adjusted by changing its shape and size through modification
      of the synthesizing process. Thus, these unique properties are very promising,
      particularly for the detection of various types of chemicals, for example boric
      acid which is a non-permitted preservative employed in food preparations. For the
      sensing material, gold (Au) nanoplates with a variety of shapes, i.e.,
      triangular, hexagonal, truncated pentagon and flat rod, were prepared using a
      seed-mediated growth method. The yield of Au nanoplates was estimated to be ca.
      63% over all areas of the sensing material. The nanoplates produced two
      absorption bands, i.e., the transverse surface plasmon resonance (t-SPR) and the
      longitudinal surface plasmon resonance (l-SPR) at 545 nm and 710 nm,
      respectively. In the sensing study, these two bands were used to examine the
      response of gold nanoplates to the presence of boric acid in an aqueous
      environment. In a typical process, when the sample is immersed into an aqueous
      solution containing boric acid, these two bands may change their intensity and
      peak centers as a result of the interaction between the boric acid and the gold
      nanoplates. The changes in the intensities and peak positions of t-SPR and l-SPR
      linearly correlated with the change in the boric acid concentration in the
      solution.

PMID- 28441324
TI  - Designing Fit for Purpose Health and Social Services for Ageing Populations.
AB  - Population ageing is occurring in all countries, regardless of the level of
      economic development. While the rising burden of chronic diseases and
      disabilities as a consequence of this demographic transition is well recognized,
      the increasing prevalence of geriatric syndromes as a public health issue is not
      as well recognized. Recently the World Health Organization's World Health and
      Ageing Report emphasized functional ability as an important outcome for aging
      populations, highlighting the concept of raising intrinsic capacity throughout
      the life course. The complementary perspective is the prevention of frailty,
      which has physical, cognitive, social and psychological dimensions. Therefore,
      services for older people should encompass medical as well as social components.
      The need and evolution for a transition in health and social services in Hong
      Kong, a special administrative region of China which has a population with the
      world's highest life expectancy, is presented as an example of how one developed
      economy attempts to meet the challenges of population ageing. There is a need to
      shift to integrated care in the community instead of specialty dominated hospital
      care, and to establish regular activities in the community to adopt and maintain
      a lifestyle that reduces frailty and disability (or promotes intrinsic capacity).
      A top down approach with financial incentives, together with public education to
      help drive policy changes, are key drivers of change. It is expected that there
      will be much heterogeneity between different countries in terms of barriers and
      facilitators, such that each country needs to document their needs and design
      appropriate services.

PMID- 28441325
TI  - The Effects of Taekwondo Training on Peripheral Neuroplasticity-Related Growth
      Factors, Cerebral Blood Flow Velocity, and Cognitive Functions in Healthy
      Children: A Randomized Controlled Trial.
AB  - Although regular Taekwondo (TKD) training has been reported to be effective for
      improving cognitive function in children, the mechanism underlying this
      improvement remains unclear. The purpose of the present study was to observe
      changes in neuroplasticity-related growth factors in the blood, assess cerebral
      blood flow velocity, and verify the resulting changes in children's cognitive
      function after TKD training. Thirty healthy elementary school students were
      randomly assigned to control (n = 15) and TKD (n = 15) groups. The TKD training
      was conducted for 60 min at a rating of perceived exertion (RPE) of 11-15, 5
      times per week, for 16 weeks. Brain-derived neurotrophic factor (BDNF), vascular
      endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) levels
      were measured by blood sampling before and after the training, and the cerebral
      blood flow velocities (peak systolic [MCAs], end diastolic [MCAd], mean cerebral
      blood flow velocities [MCAm], and pulsatility index [PI]) of the middle cerebral
      artery (MCA) were measured using Doppler ultrasonography. For cognitive function
      assessment, Stroop Color and Word Tests (Word, Color, and Color-Word) were
      administered along with other measurements. The serum BDNF, VEGF, and IGF-1
      levels and the Color-Word test scores among the sub-factors of the Stroop Color
      and Word Test scores were significantly higher in the TKD group after the
      intervention (p < 0.05). On the other hand, no statistically significant
      differences were found in any factors related to cerebral blood flow velocities,
      or in the Word test and Color test scores (p > 0.05). Thus, 16-week TKD training
      did not significantly affect cerebral blood flow velocities, but the training may
      have been effective in increasing children's cognitive function by inducing an
      increase in the levels of neuroplasticity-related growth factors.

PMID- 28441326
TI  - Adaptive Interference Cancellation of ECG Signals.
AB  - As an important biological signal, electrocardiogram (ECG) signals provide a
      valuable basis for the clinical diagnosis and treatment of several diseases.
      However, its reference significance is based on the effective acquisition and
      correct recognition of ECG signals. In fact, this mV-level weak signal can be
      easily affected by various interferences caused by the power of magnetic field,
      patient respiratory motion or contraction, and so on from the sampling terminal
      to the receiving and display end. The overlapping interference affects the
      quality of ECG waveform, leading to the false detection and recognition of wave
      groups, and thus causing misdiagnosis or faulty treatment. Therefore, the
      elimination of the interference of the ECG signal and the subsequent wave group
      identification technology has been a hot research topic, and their study has
      important significance. Based on the above, this paper introduces two improved
      adaptive algorithms based on the classical least mean square (LMS) algorithm by
      introducing symbolic functions and block-processing concepts.

PMID- 28441327
TI  - Exclusive Breastfeeding Practice and Its Association among Mothers of under 5
      Children in Kwango District, DR Congo.
AB  - The benefit of the breastfeeding has been well-established. In comparison to
      partial breast feeding, exclusive breastfeeding has even more benefits. The aim
      of this study was to identify the factors associated with breastfeeding
      exclusivity during the first 6 months of life in order to better target public
      health interventions in this community towards healthier infant nutrition and
      address child mortality in this population. A cross-sectional survey among 1145
      random households was conducted in the Kwango district of the Democratic Republic
      of the Congo (DRC) during 2 November 2015 to 13 November 2015. Women of
      reproductive age from 15-49 years and having less than 5 years old child were
      selected for the study. Chi-squared test and bivariate and multivariate analyses
      were performed using SPSS. A major finding of this study is 49.2% of the mothers
      are exclusively breastfeeding their children, and marital status, literacy, place
      of delivery, knowledge of exclusive breastfeeding and access to radio are the key
      indicators for exclusive breastfeeding. Exclusive breastfeeding rate is almost
      equivalent to the national prevalence rate for the DRC. Providing adequate
      knowledge to raise awareness of exclusive breast feeding and increase involvement
      of health care providers in enhancing knowledge through antenatal care and during
      delivery and postnatal care will be the best approaches to increase exclusive
      breastfeeding practice.

PMID- 28441328
TI  - A Gradient-Field Pulsed Eddy Current Probe for Evaluation of Hidden Material
      Degradation in Conductive Structures Based on Lift-Off Invariance.
AB  - Coated conductive structures are widely adopted in such engineering fields as
      aerospace, nuclear energy, etc. The hostile and corrosive environment leaves in
      service coated conductive structures vulnerable to Hidden Material Degradation
      (HMD) occurring under the protection coating. It is highly demanded that HMD can
      be non-intrusively assessed using non-destructive evaluation techniques. In light
      of the advantages of Gradient-field Pulsed Eddy Current technique (GPEC) over
      other non-destructive evaluation methods in corrosion evaluation, in this paper
      the GPEC probe for quantitative evaluation of HMD is intensively investigated.
      Closed-form expressions of GPEC responses to HMD are formulated via analytical
      modeling. The Lift-off Invariance (LOI) in GPEC signals, which makes the HMD
      evaluation immune to the variation in thickness of the protection coating, is
      introduced and analyzed through simulations involving HMD with variable depths
      and conductivities. A fast inverse method employing magnitude and time of the LOI
      point in GPEC signals for simultaneously evaluating the conductivity and
      thickness of HMD region is proposed, and subsequently verified by finite element
      modeling and experiments. It has been found from the results that along with the
      proposed inverse method the GPEC probe is applicable to evaluation of HMD in
      coated conductive structures without much loss in accuracy.

PMID- 28441329
TI  - Implementation of an Electronic Ionosonde to Monitor the Earth's Ionosphere via a
      Projected Column through USRP.
AB  - This document illustrates the processes carried out for the construction of an
      ionospheric sensor or ionosonde, from a universal software radio peripheral
      (USRP), and its programming using GNU-Radio and MATLAB. The development involved
      the in-depth study of the characteristics of the ionosphere, to apply the
      corresponding mathematical models used in the radar-like pulse compression
      technique and matched filters, among others. The sensor operates by firing
      electromagnetic waves in a frequency sweep, which are reflected against the
      ionosphere and are received on its return by the receiver of the instrument,
      which calculates the reflection height through the signal offset. From this
      information and a series of calculations, the electron density of the terrestrial
      ionosphere could be obtained. Improving the SNR of received echoes reduces the
      transmission power to a maximum of 400 W. The resolution associated with the
      bandwidth of the signal used is approximately 5 km, but this can be improved,
      taking advantage of the fact that the daughterboards used in the USRP allow a
      higher sampling frequency than the one used in the design of this experiment.

PMID- 28441330
TI  - Real-Time Telemetry System for Monitoring Motion of Ships Based on Inertial
      Sensors.
AB  - A telemetry system for real-time monitoring of the motions, position, speed and
      course of a ship at sea is presented in this work. The system, conceived as a
      subsystem of a radar cross-section measurement unit, could also be used in other
      applications as ships dynamics characterization, on-board cranes, antenna
      stabilizers, etc. This system was designed to be stand-alone, reliable, easy to
      deploy, low-cost and free of requirements related to stabilization procedures. In
      order to achieve such a unique combination of functionalities, we have developed
      a telemetry system based on redundant inertial and magnetic sensors and GPS
      (Global Positioning System) measurements. It provides a proper data storage and
      also has real-time radio data transmission capabilities to an on-shore station.
      The output of the system can be used either for on-line or off-line processing.
      Additionally, the system uses dual technologies and COTS (Commercial Off-The
      Shelf) components. Motion-positioning measurements and radio data link tests were
      successfully carried out in several ships of the Spanish Navy, proving the
      compliance with the design targets and validating our telemetry system.

PMID- 28441331
TI  - Improving Biometric-Based Authentication Schemes with Smart Card
      Revocation/Reissue for Wireless Sensor Networks.
AB  - User authentication in wireless sensor networks is more difficult than in
      traditional networks owing to sensor network characteristics such as unreliable
      communication, limited resources, and unattended operation. For these reasons,
      various authentication schemes have been proposed to provide secure and efficient
      communication. In 2016, Park et al. proposed a secure biometric-based
      authentication scheme with smart card revocation/reissue for wireless sensor
      networks. However, we found that their scheme was still insecure against
      impersonation attack, and had a problem in the smart card revocation/reissue
      phase. In this paper, we show how an adversary can impersonate a legitimate user
      or sensor node, illegal smart card revocation/reissue and prove that Park et
      al.'s scheme fails to provide revocation/reissue. In addition, we propose an
      enhanced scheme that provides efficiency, as well as anonymity and security.
      Finally, we provide security and performance analysis between previous schemes
      and the proposed scheme, and provide formal analysis based on the random oracle
      model. The results prove that the proposed scheme can solve the weaknesses of
      impersonation attack and other security flaws in the security analysis section.
      Furthermore, performance analysis shows that the computational cost is lower than
      the previous scheme.

PMID- 28441332
TI  - Pregnant Sheep in a Farm Environment Did Not Develop Anaemia.
AB  - The aim of this study was to document the haematological profile of pregnant ewes
      throughout gestation. Sheep were divided into three groups (n = 8 per group): non
      pregnant, singleton, or twin pregnancy. Blood samples were collected every 14
      days from day 55 of gestation for haemoglobin concentration; packed cell volume;
      total protein; and albumin concentration. On days 55 and 125 of gestation blood
      was collected for trace element estimation: soluble copper and zinc; glutathione
      peroxidase (GSHPx); and methylmalonic acid (MMA). Pooled faecal samples were
      collected on days 55, 97, and 139 of gestation. Pasture cuts were collected on
      days 97 and 153 of gestation. The haematology and protein concentrations were not
      different between groups throughout the study. Copper concentration increased in
      all animals during the study (p < 0.0001). Zinc concentration was lowest in the
      singleton and twin pregnant sheep on day 55 of gestation (p = 0.04). GSHPx was
      not different between groups during the study. MMA decreased in all animals
      during the study (p < 0.0001), but was not different between groups. Faecal
      samples were consistently negative for strongyle and nematode eggs, and coccidian
      oocysts. The pasture was good quality. Pregnant sheep in a farm environment with
      normal trace element status, no parasites, and an adequate diet, did not develop
      anaemia (PCV < 0.27).

PMID- 28441333
TI  - How Are Service Dogs for Adults with Post Traumatic Stress Disorder Integrated
      with Rehabilitation in Denmark? A Case Study.
AB  - A severe mental illness like Post Traumatic Stress Disorder (PTSD) is known to
      have psychosocial consequences that can lead to a decreased quality of life.
      Research in Animal-Assisted Therapy (AAT) has revealed that the presence of a dog
      can have a positive effect on health, e.g., increase quality of life and lessen
      depression and anxiety. However, canine companionship is not a catch-all
      solution. Previous research has revealed methodological limitations that prohibit
      any clear conclusions, as well as a sparsity of critical reflection in anecdotal
      reports and case studies, which means that more research is needed to
      contextualize the findings. There has been an increasing interest in animal
      assisted intervention in Denmark in recent years. Previously, authorities could
      only grant service dogs to adults with physical disabilities, but now this has
      been extended to adults with mental illnesses. Therefore, it has become important
      to explore how these service dogs are incorporated into rehabilitation practices
      in mental health, and how rehabilitation professionals react to the use of
      service dogs. This paper is a case study of a person who suffers from PTSD. This
      study examines how the person describes the significance of having a dog during
      her rehabilitation process, and how this is integrated with existing
      rehabilitation. The case study has been developed based on a semi-structured
      interview. A Thematic Content analysis was used to reveal dominant patterns and
      categories. This study revealed a lack of communication and collaboration between
      public administration (social service), service dog providers, health
      rehabilitation services, and providers of psychological treatment. It also
      revealed limited access for the dog to public services, limited success in
      incorporating the dog into goal-directed treatment and rehabilitation procedures,
      a strongly felt emotional support from the dog, and a perceived stigma by having
      the dog wearing a vest with he words "mentally ill" printed on it.

PMID- 28441334
TI  - Peptidyl Transferase Center and the Emergence of the Translation System.
AB  - In this work, the three-dimensional (3D) structure of the ancestral Peptidyl
      Transferase Center (PTC) built by concatamers of ancestral sequences of tRNAs was
      reconstructed, and its possible interactions with tRNAs molecules were analyzed.
      The 3D structure of the ancestral PTC was also compared with the current PTC of
      T. thermophilus. Docking experiments between the ancestral PTC and tRNAs suggest
      that in the origin of the translation system, the PTC functioned as an adhesion
      center for tRNA molecules. The approximation of tRNAs charged with amino acids to
      the PTC permitted peptide synthesis without the need of a genetic code.

PMID- 28441335
TI  - Systematic Review of Cognitive-Behavioural Therapy for Social Anxiety Disorder in
      Psychosis.
AB  - BACKGROUND: Social anxiety is highly prevalent among people with psychosis and
      linked with significant social disability and poorer prognosis. Although
      cognitive-behavioural therapy (CBT) has shown to be effective for the treatment
      of social anxiety in non-psychotic populations, there is a lack of evidence on
      the clinical effectiveness of CBT for the treatment of social anxiety when this
      is co-morbid in psychosis. METHODS: A systematic review to summarise and
      critically appraise the literature on the effectiveness of CBT interventions for
      the treatment of social anxiety in psychosis. RESULTS: Two studies were included
      in the review assessing the effectiveness of group CBT for social anxiety in
      schizophrenia, both of poor methodological quality. Preliminary findings suggest
      that group-based CBT is effective in treating symptoms of social anxiety,
      depression and associated distress in people with schizophrenia. CONCLUSION: The
      evidence-base is not robust enough to provide clear implications for practice
      about the effectiveness of CBT for the treatment of social anxiety in psychosis.
      Future research should focus on methodologically rigorous randomised controlled
      trials with embedded process evaluation to assess the effectiveness of CBT
      interventions in targeting symptoms of social anxiety in psychosis and identify
      mechanisms of change.

PMID- 28441336
TI  - Neurobehavioral Outcomes of Mild Traumatic Brain Injury: A Mini Review.
AB  - Traumatic brain injury outcomes can be classified as acute or chronic. Acute
      outcomes refer to injuries that occur immediately at the time of the injury and
      subsequent short-term consequences. Chronic outcomes refer to adverse outcomes
      that are more long-term. In mild traumatic brain injury, recovery from acute
      outcomes typically occurs very rapidly, i.e., within 2 weeks, with full recovery
      expected by 90 days. However, some 10%-15% individuals can remain symptomatic for
      much longer with an outcome termed post-concussive syndrome. This outcome is
      difficult to predict since there are very few rigorous, prospective studies of
      this syndrome.

PMID- 28441337
TI  - A Study of the Differential Effects of Eicosapentaenoic Acid (EPA) and
      Docosahexaenoic Acid (DHA) on Gene Expression Profiles of Stimulated Thp-1
      Macrophages.
AB  - Background: An appropriate intake of omega-3 (n-3) fatty acids (FAs) such as
      eicosapentaenoic and docosahexaenoic acid (EPA/DHA) from marine sources is known
      to have anti-inflammatory effects. However, molecular mechanisms underlying their
      beneficial effects on health are not fully understood. The aim of the present
      study was to characterize gene expression profiles of THP-1 macrophages,
      incubated in either EPA or DHA and stimulated with lipopolysaccharide (LPS), a
      pro-inflammatory agent. Methods: THP-1 macrophages were incubated into 10, 50 and
      75 uM of EPA or DHA for 24 h, and 100 nM of LPS was added to the culture media
      for 18 h. Total mRNA was extracted and gene expression examined by microarray
      analysis using Illumina Human HT-12 expression beadchips (Illumina). Results:
      Pathway analysis revealed that EPA and DHA regulate genes involved in cell cycle
      regulation, apoptosis, immune response and inflammation, oxidative stress and
      cancer pathways in a differential and dose-dependent manner. Conclusions: EPA and
      DHA appear to exert differential effects on gene expression in THP-1 macrophages.
      Specific effects of n-3 FAs on gene expression levels are also dose-dependent.

PMID- 28441338
TI  - Effects of 3D-Printed Polycaprolactone/beta-Tricalcium Phosphate Membranes on
      Guided Bone Regeneration.
AB  - This study was conducted to compare 3D-printed polycaprolactone (PCL) and
      polycaprolactone/beta-tricalcium phosphate (PCL/beta-TCP) membranes with a
      conventional commercial collagen membrane in terms of their abilities to
      facilitate guided bone regeneration (GBR). Fabricated membranes were tested for
      dry and wet mechanical properties. Fibroblasts and preosteoblasts were seeded
      into the membranes and rates and patterns of proliferation were analyzed using a
      kit-8 assay and by scanning electron microscopy. Osteogenic differentiation was
      verified by alizarin red S and alkaline phosphatase (ALP) staining. An in vivo
      experiment was performed using an alveolar bone defect beagle model, in which
      defects in three dogs were covered with different membranes. CT and histological
      analyses at eight weeks after surgery revealed that 3D-printed PCL/beta-TCP
      membranes were more effective than 3D-printed PCL, and substantially better than
      conventional collagen membranes in terms of biocompatibility and bone
      regeneration and, thus, at facilitating GBR.

PMID- 28441339
TI  - Still Searching: A Meta-Synthesis of a Good Death from the Bereaved Family Member
      Perspective.
AB  - The concept of a good death continues to receive attention in end-of-life (EOL)
      scholarship. We sought to continue this line of inquiry related to a good death
      by conducting a meta-synthesis of published qualitative research studies that
      examined a good death from the bereaved family member's perspective. Results of
      the meta-synthesis included 14 articles with 368 participants. Based on analysis,
      we present a conceptual model called The Opportunity Model for Presence during
      the EOL Process. The model is framed in socio-cultural factors, and major themes
      include EOL process engagement with categories of healthcare participants,
      communication and practical issues. The second theme, (dis)continuity of care,
      includes categories of place of care, knowledge of family member dying and moment
      of death. Both of these themes lead to perceptions of either a good or bad death,
      which influences the bereavement process. We argue the main contribution of the
      model is the ability to identify moments throughout the interaction where family
      members can be present to the EOL process. Recommendations for healthcare
      participants, including patients, family members and clinical care providers are
      offered to improve the quality of experience throughout the EOL process and
      limitations of the study are discussed.

PMID- 28441340
TI  - Selection, Characterization and Interaction Studies of a DNA Aptamer for the
      Detection of Bifidobacterium bifidum.
AB  - A whole-bacterium-based SELEX (Systematic Evolution of Ligands by Exponential
      Enrichment) procedure was adopted in this study for the selection of an ssDNA
      aptamer that binds to Bifidobacterium bifidum. After 12 rounds of selection
      targeted against B. bifidum, 30 sequences were obtained and divided into seven
      families according to primary sequence homology and similarity of secondary
      structure. Four FAM (fluorescein amidite) labeled aptamer sequences from
      different families were selected for further characterization by flow cytometric
      analysis. The results reveal that the aptamer sequence CCFM641-5 demonstrated
      high-affinity and specificity for B. bifidum compared with the other sequences
      tested, and the estimated Kd value was 10.69 +/- 0.89 nM. Additionally, sequence
      truncation experiments of the aptamer CCFM641-5 led to the conclusion that the 5'
      primer and 3'-primer binding sites were essential for aptamer-target binding. In
      addition, the possible component of the target B. bifidum, bound by the aptamer
      CCFM641-5, was identified as a membrane protein by treatment with proteinase.
      Furthermore, to prove the potential application of the aptamer CCFM641-5, a
      colorimetric bioassay of the sandwich-type structure was used to detect B.
      bifidum. The assay had a linear range of 104 to 107 cfu/mL (R2 = 0.9834).
      Therefore, the colorimetric bioassay appears to be a promising method for the
      detection of B. bifidum based on the aptamer CCFM641-5.

PMID- 28441341
TI  - A Long-Term Treatment with Arachidonyl-2'-Chloroethylamide Combined with
      Valproate Increases Neurogenesis in a Mouse Pilocarpine Model of Epilepsy.
AB  - Rational polytherapy in the treatment of refractory epilepsy has been the main
      therapeutic modality for several years. In treatment with two or more
      antiepileptic drugs (AEDs), it is of particular importance that AEDs be selected
      based on their high anticonvulsant properties, minimal side effects, and impact
      on the formation of new neurons. The aim of the study was to conduct an in vivo
      evaluation of the relationship between treatments with synthetic cannabinoid
      arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid
      (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy. All
      studies were performed on adolescent male CB57/BL mice with using the following
      drugs: VPA (10 mg/kg), ACEA (10 mg/kg), phenylmethylsulfonyl fluoride (PMSF-a
      substance protecting ACEA against degradation by fatty acid hydrolase, 30 mg/kg),
      pilocarpine (PILO, a single dose of 290 mg/kg) and methylscopolamine (30 min
      before PILO to stop peripheral cholinergic effects of pilocarpine, 1 mg/kg). We
      evaluated the process of neurogenesis after a 10-day treatment with ACEA and VPA,
      alone and in combination. We observed a decrease of neurogenesis in the PILO
      control group as compared to the healthy control mice. Furthermore, ACEA + PMSF
      alone and in combination with VPA significantly increased neurogenesis compared
      to the PILO control group. In contrast, VPA 10-day treatment had no impact on the
      level of neurons in comparison to the PILO control group. The combination of
      ACEA, PMSF and VPA considerably stimulated the process of creating new cells,
      particularly neurons, while chronic administration of VPA itself had no influence
      on neurogenesis in the mouse pilocarpine model of epilepsy. The obtained results
      enabled an in vivo evaluation of neurogenesis after treatment with antiepileptic
      drugs in an experimental model of epilepsy.

PMID- 28441343
TI  - Immune-Stimulatory Effects of Althaea rosea Flower Extracts through the MAPK
      Signaling Pathway in RAW264.7 Cells.
AB  - Althaea rosea (Linn.) is a medicinal plant from China and Korea that has been
      traditionally used to control inflammation, to stop bedwetting and as a mouthwash
      in cases of bleeding gums. Its flowers are employed medicinally for their
      emollient, demulcent and diuretic properties, which make them useful in chest
      complaints. Furthermore, a flower extract decoction is used to improve blood
      circulation, for the treatment of constipation, dysmenorrhoea, haemorrhages, etc.
      However, the possible mechanisms of the immune-stimulatory effect remains to be
      elucidated. Therefore, we investigated the role of Althaea rosea flower (ARF)
      extracts in the immune-stimulatory effect of macrophages and the underlying
      mechanisms of action. ARF water extract (ARFW) could dose-dependently increase NO
      production and cytokines (IL-6 and TNF-alpha). We also found that ARFW
      significantly increased the expression of iNOS and COX-2 proteins in RAW264.7
      cells. Consistent with these results, MAPK protein (JNK, ERK, p38) expression
      levels were induced after treatment with ARFW. Additionally, ARFW showed a marked
      increase in the phosphorylation level of IkappaBalpha and subsequent IkappaBalpha
      degradation allowing NF-kappaB nuclear translocation. These results suggest that
      the immune-stimulatory effect of A. rosea flower extracts is mediated through the
      translocation of NF-kappaB p65 subunit into the nucleus from the cytoplasm and
      subsequent activation of pro-inflammatory cytokines (IL-6 and TNF-alpha) and
      other mediators (iNOS and COX-2), which occurs mainly through MAPK signalling
      pathway. Thus, we suggest that ARFW could be considered as a potential
      therapeutic agent useful in the development of immune-stimulatory compounds.

PMID- 28441342
TI  - Of Oestrogens and Sperm: A Review of the Roles of Oestrogens and Oestrogen
      Receptors in Male Reproduction.
AB  - The crucial role that oestrogens play in male reproduction has been generally
      accepted; however, the exact mechanism of their action is not entirely clear and
      there is still much more to be clarified. The oestrogen response is mediated
      through oestrogen receptors, as well as classical oestrogen receptors' variants,
      and their specific co-expression plays a critical role. The importance of
      oestrogen signalling in male fertility is indicated by the adverse effects of
      selected oestrogen-like compounds, and their interaction with oestrogen receptors
      was proven to cause pathologies. The aims of this review are to summarise the
      current knowledge on oestrogen signalling during spermatogenesis and sperm
      maturation and discuss the available information on oestrogen receptors and their
      splice variants. An overview is given of species-specific differences including
      in humans, along with a detailed summary of the methodology outcome, including
      all the genetically manipulated models available to date. This review provides
      coherent information on the recently discovered mechanisms of oestrogens' and
      oestrogen receptors' effects and action in both testicular somatic and germ
      cells, as well as in mature sperm, available for mammals, including humans.

PMID- 28441344
TI  - Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons
      from the Common Sea Urchin Tissue.
AB  - Scaffolds for tissue engineering application may be made from a collagenous
      extracellular matrix (ECM) of connective tissues because the ECM can mimic the
      functions of the target tissue. The primary sources of collagenous ECM material
      are calf skin and bone. However, these sources are associated with the risk of
      having bovine spongiform encephalopathy or transmissible spongiform
      encephalopathy. Alternative sources for collagenous ECM materials may be derived
      from livestock, e.g., pigs, and from marine animals, e.g., sea urchins.
      Collagenous ECM of the sea urchin possesses structural features and mechanical
      properties that are similar to those of mammalian ones. However, even more
      intriguing is that some tissues such as the ligamentous catch apparatus can
      exhibit mutability, namely rapid reversible changes in the tissue mechanical
      properties. These tissues are known as mutable collagenous tissues (MCTs). The
      mutability of these tissues has been the subject of on-going investigations,
      covering the biochemistry, structural biology and mechanical properties of the
      collagenous components. Recent studies point to a nerve-control system for
      regulating the ECM macromolecules that are involved in the sliding action of
      collagen fibrils in the MCT. This review discusses the key attributes of the
      structure and function of the ECM of the sea urchin ligaments that are related to
      the fibril-fibril sliding action-the focus is on the respective components within
      the hierarchical architecture of the tissue. In this context, structure refers to
      size, shape and separation distance of the ECM components while function is
      associated with mechanical properties e.g., strength and stiffness. For
      simplicity, the components that address the different length scale from the
      largest to the smallest are as follows: collagen fibres, collagen fibrils,
      interfibrillar matrix and collagen molecules. Application of recent theories of
      stress transfer and fracture mechanisms in fibre reinforced composites to a wide
      variety of collagen reinforcing (non-mutable) connective tissue, has allowed us
      to draw general conclusions concerning the mechanical response of the MCT at
      specific mechanical states, namely the stiff and complaint states. The intent of
      this review is to provide the latest insights, as well as identify technical
      challenges and opportunities, that may be useful for developing methods for
      effective mechanical support when adapting decellularised connective tissues from
      the sea urchin for tissue engineering or for the design of a synthetic analogue.

PMID- 28441345
TI  - Levels and Distribution of Pollutants in the Waters of an Aquatic Ecosystem in
      Northern Mexico.
AB  - The availability of good quality water resources is essential to ensure healthy
      crops and livestock. The objective of this study was to evaluate the level of
      pollution in Bustillos Lagoon in northern Mexico. Physical-chemical parameters
      like sodium, chloride, sulfate, electrical conductivity, nitrates, and the
      pesticide dichlorodiphenyltrichloroethane (DDT) were analyzed to determine the
      water quality available in the lagoon. Although DDT has been banned in several
      countries, it is still used for agricultural purposes in Mexico and its presence
      in this area had not been analyzed previously. Bustillos Lagoon was divided into
      three zones for the evaluation: (1) industrial; (2) communal lands; and (3)
      agricultural. The highest concentrations of sodium (2360 mg/L) and SAR (41 meq/L)
      reported in the industrial zone are values exceeding the United Nations Food and
      Agricultural Organization (FAO) irrigation water quality guidelines. DDT and its
      metabolites were detected in all of the 21 sites analyzed, in the agricultural
      zone ?DDTs = 2804 ng/mL, this level is much higher than those reported for other
      water bodies in Mexico and around the world where DDT has been used heavily. The
      water in the communal zone is the least contaminated, but can only be recommended
      for irrigation of plants with high stress tolerance and not for crops.

PMID- 28441346
TI  - Xanthones from the Pericarp of Garcinia mangostana.
AB  - Mangosteen (Garcinia mangostana L.) is one of the most popular tropical fruits
      (called the "Queen of Fruits"), and is a rich source of oxygenated and prenylated
      xanthone derivatives. In the present work, phytochemical investigation has
      resulted in one new prenylated xanthone and 13 known xanthones isolated from the
      pericarp of G. mangostana. Their structures were established by spectroscopic
      data analysis, including X-ray diffraction. The new one was further tested for
      cytotoxic activity against seven cancer cell lines (CNE-1, CNE-2, A549, H490, PC
      3, SGC-7901, U87), displaying the half maximal inhibitory concentration (IC50)
      values 3.35, 4.01, 4.84, 7.84, 6.21, 8.09, and 6.39 MUM, respectively. It is
      noteworthy that the new compound can promote CNE-2 cells apoptosis in late stage,
      having a remarkable inhibition effect on the side population growth of CNE-2 at
      1.26 MUM. The bioactive compound was also detected in extract from fresh
      mangosteen flesh, which indicated that the popular fruit could have potential
      cytotoxic activity for cancer cell lines.

PMID- 28441347
TI  - Association between Sleep and Body Weight: A Panel Data Model Based on a
      Retrospective Longitudinal Cohort of Chinese Infants.
AB  - The focus of this article is on sleep duration and sleep problems in infants and
      their association with body weight. A retrospective birth cohort of 519 infants
      was enrolled in a community-based study conducted in Changsha, China. Infant
      weight and other health-related information were collected during regular
      standard checkups at the Community Health Service Centers when infants were 1, 3,
      6, 8, and 12 months old. The sleep duration and sleep problems of infants were
      assessed by maternal self-reports. Panel data model was used to evaluate the
      association of sleep duration and sleep problems with infant body weight.
      Significant relevance between self-reported sleep duration and weight of infants
      has been reported in the literature tested by the fixed effects model (p < 0.01).
      However, this study indicated that sleep problems of infants had no effect on
      their weight (p = 0.151), after adjusting feeding patterns and socioeconomic
      factors of their families. This paper argues that, as a potentially modifiable
      risk factor, infant sleep duration deserves more attention from their parents and
      families in order to prevent and control overweight or obesity in infants as well
      as reducing the incidence of obesity in adults.

PMID- 28441348
TI  - Deoxynucleoside Salvage in Fission Yeast Allows Rescue of Ribonucleotide
      Reductase Deficiency but Not Spd1-Mediated Inhibition of Replication.
AB  - In fission yeast, the small, intrinsically disordered protein S-phase delaying
      protein 1 (Spd1) blocks DNA replication and causes checkpoint activation at least
      in part, by inhibiting the enzyme ribonucleotide reductase, which is responsible
      for the synthesis of DNA. The CRL4Cdt2 E3 ubiquitin ligase mediates degradation
      of Spd1 and the related protein Spd2 at S phase of the cell cycle. We have
      generated a conditional allele of CRL4Cdt2, by expressing the highly unstable
      substrate-recruiting protein Cdt2 from a repressible promoter. Unlike Spd1, Spd2
      does not regulate deoxynucleotide triphosphate (dNTP) pools; yet we find that
      Spd1 and Spd2 together inhibit DNA replication upon Cdt2 depletion. To directly
      test whether this block of replication was solely due to insufficient dNTP
      levels, we established a deoxy-nucleotide salvage pathway in fission yeast by
      expressing the human nucleoside transporter human equilibrative nucleoside
      transporter 1 (hENT1) and the Drosophila deoxynucleoside kinase. We present
      evidence that this salvage pathway is functional, as 2 uM of deoxynucleosides in
      the culture medium is able to rescue the growth of two different temperature
      sensitive alleles controlling ribonucleotide reductase. However, salvage
      completely failed to rescue S phase delay, checkpoint activation, and damage
      sensitivity, which was caused by CRL4Cdt2 inactivation, suggesting that Spd1-in
      addition to repressing dNTP synthesis-together with Spd2, can inhibit other
      replication functions. We propose that this inhibition works at the point of the
      replication clamp proliferating cell nuclear antigen, a co-factor for DNA
      replication.

PMID- 28441349
TI  - Correction: Chon-Kit Chou, et al. The Regulations of Deubiquitinase USP15 and Its
      Pathophysiological Mechanisms in Diseases. Int. J. Mol. Sci. 2017, 18, 483.
AB  - n/a.

PMID- 28441350
TI  - Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as
      Antibacterial Agents.
AB  - In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran
      derivatives were designed, synthesized and evaluated for their antibacterial
      activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus
      aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC
      43300, and Streptococcus faecalis (S. faecalis) ATCC 29212) and one Gram-(-)
      strain (Escherichia coli (E. coli) ATCC 25922). The 2-salicyloylbenzofuran
      heterocycles were generated by Rap-Stoermer condensation of salicylaldehydes with
      phenacyl bromides and then converted to diverse O-ether derivatives by Williamson
      synthesis. The targeted products were screened for in vitro qualitative (zone of
      inhibition) and quantitative (MIC) antibacterial activities by agar well
      diffusion assay and agar dilution method. Amongst the compounds, those bearing
      carboxylic acid functional group were found to exhibit reasonable activity
      against Gram-(+) bacterial strains including S. faecalis, MSSA and MRSA with the
      most potent antibacterial agent 8h (MICs = 0.06-0.12 mM). Besides, the 2
      salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the
      best MICs = 0.14 mM (8f) and 0.12 mM (8h). Finally, the antibacterial results
      preliminarily suggested that the substituent bearing carboxylic acid group at
      salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the
      functionality necessary for antibacterial activities.

PMID- 28441351
TI  - Probing Temperature- and pH-Dependent Binding between Quantum Dots and Bovine
      Serum Albumin by Fluorescence Correlation Spectroscopy.
AB  - Luminescent quantum dots (QDs) with unique optical properties have potential
      applications in bio-imaging. The interaction between QDs and bio-molecules is
      important to the biological effect of QDs in vivo. In this paper, we have
      employed fluorescence correlation spectroscopy (FCS) to probe the temperature-
      and pH-dependent interactions between CdSe QDs with carboxyl (QDs-COOH) and
      bovine serum albumin (BSA) in buffer solutions. The results have shown that
      microscopic dissociation constant K'D is in the range of (1.5 +/- 0.2) * 10-5 to
      (8.6 +/- 0.1) * 10-7 M, the Hill coefficient n is from 0.4 to 2.3, and the
      protein corona thickness is from 3.0 to 9.4 nm. Variable-temperature measurements
      have shown both negative values of ?H and ?S for BSA adsorption on QDs-COOH,
      while pH has a profound effect on the adsorption. Additional, FCS measurement QDs
      COOH and proteins in whole mice serum and plasma samples has also been conducted.
      Finally, simulation results have shown four favored QD binding sites in BSA.

PMID- 28441352
TI  - High-Throughput Determination of Sodium Danshensu in Beagle Dogs by the LCMS/MS
      Method, Employing Liquid-Liquid Extraction Based on 96-Well Format Plates.
AB  - Sodium Danshensu (sodium d-(+)-beta-(3,4-dihydroxyphenyl) lactate), one of the
      water-soluble ingredients in Salvia miltiorrhiza, exhibits potent relaxation of
      the coronary artery and anticoagulation effection. A high-throughput, rapid, and
      sensitive method combining liquid chromatography with electrospray ionization
      tandem mass spectrometry to determine the sodium danshensu in beagle dog plasma
      was developed and validated, using gallic acid as an internal standard (IS).
      Acidified plasma samples were extracted using 96-well liquid-liquid extraction,
      and were eluted on a CNW Athena C18 column (3 MUm, 2.1 * 100 mm) by using a
      gradient mobile phase system of methanol and water (containing 0.2% formic acid).
      The mass spectrometric detection was achieved using negative ion electrospray
      ionization mode and monitoring the precursor->production combinations of m/z 197
      >135 for sodium danshensu and 169->125 for IS, in multiple reaction monitoring
      modes. Good linearity was achieved, and the linear range was 10-1000 ng/mL (R2 >
      0.996) with a quantification limit of 10 ng/mL for sodium danshensu in beagle dog
      plasma. The intra- and inter-day precision (RSD) ranged from 2.1% to 9.0%. The
      accuracy (RE) was between -8.6% and 5.7% at all quality control levels. The
      validated method was successfully applied to the pharmacokinetics study of sodium
      danshensu in beagle dog plasma after intravenous injection and oral
      administration of sodium danshensu.

PMID- 28441354
TI  - Design and Development of a Three-Component Force Sensor for Milling Process
      Monitoring.
AB  - A strain-type three-component table dynamometer is presented in this paper, which
      reduces output errors produced by cutting forces imposed on the different milling
      positions of a workpiece. A sensor structure with eight parallel elastic beams is
      proposed, and sensitive regions and Wheastone measuring circuits are also
      designed in consideration of eliminating the influences of the eccentric forces.
      To evaluate the sensor decoupling performance, both of the static calibration and
      dynamic milling test were implemented in different positions of the workpiece.
      Static experiment results indicate that the maximal deviation between the
      measured forces and the standard inputs is 4.58%. Milling tests demonstrate that
      with same machining parameters, the differences of the measured forces between
      different milling positions derived by the developed sensor are no larger than
      6.29%. In addition, the natural frequencies of the dynamometer are kept higher
      than 2585.5 Hz. All the measuring results show that as a strain-type dynamometer,
      the developed force sensor has an improved eccentric decoupling accuracy with
      natural frequencies not much decreased, which owns application potential in
      milling process monitoring.

PMID- 28441353
TI  - Matrix Metalloproteinase Gene Activation Resulting from Disordred Epigenetic
      Mechanisms in Rheumatoid Arthritis.
AB  - Matrix metalloproteinases (MMPs) are implicated in the degradation of
      extracellular matrix (ECM). Rheumatoid arthritis (RA) synovial fibroblasts (SFs)
      produce matrix-degrading enzymes, including MMPs, which facilitate cartilage
      destruction in the affected joints in RA. Epigenetic mechanisms contribute to
      change in the chromatin state, resulting in an alteration of gene transcription.
      Recently, MMP gene activation has been shown to be caused in RASFs by the
      dysregulation of epigenetic changes, such as histone modifications, DNA
      methylation, and microRNA (miRNA) signaling. In this paper, we review the role of
      MMPs in the pathogenesis of RA as well as the disordered epigenetic mechanisms
      regulating MMP gene activation in RASFs.

PMID- 28441356
TI  - A Simple, Cost-Effective Sensor for Detecting Lead Ions in Water Using Under
      Potential Deposited Bismuth Sub-Layer with Differential Pulse Voltammetry (DPV).
AB  - This research has developed a simple to use, cost effective sensor system for the
      detection of lead ions in tap water. An under-potential deposited bismuth sub
      layer on a thin gold film based electrochemical sensor was designed,
      manufactured, and evaluated. Differential pulse voltammetry (DPV) measurement
      technique was employed in this detection. Tap water from the Cleveland, OH, USA
      regional water district was the test medium. Concentrations of lead ion in the
      range of 8 * 10-7 M to 5 * 10-4 M were evaluated, showing a good sensitivity over
      this concentration range. The calibration curve for the DPV measurements of lead
      ions in tap water showed excellent reproducibility with R2 value of 0.970. This
      DPV detection system required 3-6 min to complete the detection measurement. A
      longer measurement time of 6 min was used for the lower lead ion concentration.
      The selectivity of this lead ion sensor was very good, and Fe III, Cu II, Ni II,
      and Mg II at a concentration level of 5 * 10-4 M did not interfere with the lead
      ion measurement.

PMID- 28441355
TI  - 188Re-Liposome Can Induce Mitochondrial Autophagy and Reverse Drug Resistance for
      Ovarian Cancer: From Bench Evidence to Preliminary Clinical Proof-of-Concept.
AB  - Despite standard treatment, about 70% of ovarian cancer will recur. Cancer stem
      cells (CSCs) have been implicated in the drug-resistance mechanism. Several drug
      resistance mechanisms have been proposed, and among these, autophagy plays a
      crucial role for the maintenance and tumorigenicity of CSCs. Compared to their
      differentiated counterparts, CSCs have been demonstrated to display a
      significantly higher level of autophagy flux. Moreover, mitophagy, a specific
      type of autophagy that selectively degrades excessive or damaged mitochondria, is
      shown to contribute to cancer progression and recurrence in several types of
      tumors. Nanomedicine has been shown to tackle the CSCs problem by overcoming drug
      resistance. In this work, we developed a nanomedicine, 188Re-liposome, which was
      demonstrated to target autophagy and mitophagy in the tumor microenvironment. Of
      note, the inhibition of autophagy and mitophagy could lead to significant tumor
      inhibition in two xenograft animal models. Lastly, we presented two cases of
      recurrent ovarian cancer, both in drug resistance status that received a level I
      dose from a phase I clinical trial. Both cases developing drug resistance showed
      drug sensitivity to 188Re-liposome. These results suggest that inhibition of
      autophagy and mitophagy by a nanomedicine may be a novel strategy to overcome
      drug resistance in ovarian cancer.

PMID- 28441357
TI  - Investigation of the Anti-Leishmania (Leishmania) infantum Activity of Some
      Natural Sesquiterpene Lactones.
AB  - Leishmaniases are neglected infectious diseases caused by parasites of the
      'protozoan' genus Leishmania. Depending on the parasite species, different
      clinical forms are known as cutaneous, muco-cutaneous, and the visceral
      leishmaniasis (VL). VL is particularly fatal and the therapy presents
      limitations. In the search for new anti-leishmanial hit compounds, seven natural
      sesquiterpene lactones were evaluated against promastigotes and intracellular
      amastigotes of Leishmania (Leishmania) infantum, a pathogen causing VL. The
      pseudoguaianolides mexicanin I and helenalin acetate demonstrated the highest
      selectivity and potency against intracellular amastigotes. In addition,
      promastigotes treated with helenalin acetate were subject to an ultrastructural
      and biochemical investigation. The lethal action of the compound was investigated
      by fluorescence-activated cell sorting and related techniques to detect
      alterations in reactive oxygen species (ROS) content, plasma membrane
      permeability, and mitochondrial membrane potential. Helenalin acetate
      significantly reduced the mitochondrial membrane potential and the mitochondrial
      structural damage was also confirmed by transmission electron microscopy,
      displaying an intense organelle swelling. No alteration of plasma membrane
      permeability or ROS content could be detected. Additionally, helenalin acetate
      significantly increased the production of nitric oxide in peritoneal macrophages,
      probably potentiating the activity against the intracellular amastigotes.
      Helenalin acetate could hence be a useful anti-leishmanial scaffold for further
      optimization studies.

PMID- 28441358
TI  - Comparison of a Web-Based 24-h Dietary Recall Tool (Foodbook24) to an Interviewer
      Led 24-h Dietary Recall.
AB  - Web-based tools have the potential to reduce the cost of dietary assessment;
      however, it is necessary to establish their performance compared to traditional
      dietary assessment methods. This study aims to compare nutrient and food intakes
      derived from Foodbook24 to those obtained from an interview-led 24-h dietary
      recall (24HDR). Seventy-nine adult participants completed one self-administered
      24HDR using Foodbook24 and one interviewer-led 24HDR on the same day. Following a
      10 days wash-out period the same process was completed again in opposite order to
      the previous study visit. Statistical analysis including Spearman's rank order
      correlation, Mann-Whitney U tests, cross-classification analysis, and "Match",
      "Omission", and "Intrusion" rates were used to investigate the relationship
      between both methods. Strong, positive correlations of nutrient intake estimated
      using both methods was observed (rs = 0.6-1.0; p < 0.001). The percentage of
      participants classified into the same tertile of nutrient intake distribution
      using both methods ranged from 58% (energy) to 82% (vitamin D). The overall match
      rate for food intake between both methods was 85%, while rates for omissions and
      intrusions were 11.5% and 3.5%, respectively. These results, alongside the
      reduced cost and participant burden associated with Foodbook24, highlight the
      tool's potential as a viable alternative to the interviewer-led 24HDR.

PMID- 28441359
TI  - Relationship between Expression of Chalcone Synthase Genes and Chromones in
      Artificial Agarwood induced by Formic Acid Stimulation Combined with Fusarium sp.
      A2 Inoculation.
AB  - Agarwood (gaharu) is a fragrant resin produced in the heartwood of resinous
      Gyrinops and Aquilaria species. Artificial agarwood samples were obtained from
      Aquilaria sinensis (Lour.) Gilg using formic acid (FA) stimulation combined with
      Fusarium sp. A2 inoculation. The relationship between the expression of chalcone
      synthase genes (CHS) and dynamic changes in chromone content was explored in
      resin-deposited parts of the trunks of A. sinensis. CHS gene expression levels
      were detected by qRT-PCR analysis. The chemical composition of agarwood obtained
      from the heartwood of A. sinensis before and within 1 year after induction was
      determined by GC-MS. After induction with FA stimulation combined with F. sp. A2
      inoculation, the CHS1 gene showed relatively high expression, whereas the CHS2
      gene showed low expression. The relative gene expression level of CHS1 peaked at
      12 months, with a 153.1-fold increase, and the dominant period of the CHS2 gene
      expression was 10 months with a 14.13-fold increase. Moreover, chromones were not
      detected until after 2 months, and a large proportion of chromone compounds were
      detected after 4 months. Chromone content increased with time and peaked at 12
      months. CHS1 gene expression was significantly correlated with 6-hydroxy-2-(2
      phenylethyl)chromone accumulation, and CHS2 gene expression was significantly
      correlated with 5-hydroxy-6-methoxy-2-(2-phenylethyl)chromone accumulation. CHS
      gene expression was extremely sensitive to FA stimulation combined with F. sp. A2
      inoculation and responded to late-onset injury. CHS genes expression also
      preceded the chromone accumulation. This work laid the foundation for studies on
      the mechanism by which genes regulate chromone biosynthesis pathways during the
      formation of agarwood resin in A. sinensis.

PMID- 28441360
TI  - Erythromycin Modification That Improves Its Acidic Stability while Optimizing It
      for Local Drug Delivery.
AB  - The antibiotic erythromycin has limited efficacy and bioavailability due to its
      instability and conversion under acidic conditions via an intramolecular
      dehydration reaction. To improve the stability of erythromycin, several analogs
      have been developed-such as azithromycin and clarithromycin-which decrease the
      rate of intramolecular dehydration. We set out to build upon this prior work by
      developing a conjugate of erythromycin with improved pH stability,
      bioavailability, and preferential release from a drug delivery system directly at
      the low pH of an infection site. To develop this new drug conjugate, adamantane-1
      carbohydrazide was covalently attached to erythromycin via a pH-degradable
      hydrazone bond. Since Staphylococcus aureus infection sites are slightly acidic,
      the hydrazone bond will undergo hydrolysis liberating erythromycin directly at
      the infection site. The adamantane group provides interaction with the drug
      delivery system. This local delivery strategy has the potential of reducing off
      target and systemic side-effects. This work demonstrates the synthesis of a pH
      cleavable, erythromycin conjugate that retains the inherent antimicrobial
      activity of erythromycin, has an increased hydrophobicity, and improved stability
      in acidic conditions; thereby enhancing erythromycin's bioavailability while
      simultaneously reducing its toxicity.

PMID- 28441361
TI  - Immunization Strategies Targeting Newly Arrived Migrants in Non-EU Countries of
      the Mediterranean Basin and Black Sea.
AB  - Background: The World Health Organization recommends that host countries ensure
      appropriate vaccinations to refugees, asylum seekers and migrants. However,
      information on vaccination strategies targeting migrants in host countries is
      limited. Methods: In 2015-2016 we carried out a survey among national experts
      from governmental bodies of 15 non-EU countries of the Mediterranean and Black
      Sea in order to document and share national vaccination strategies targeting
      newly arrived migrants. Results: Four countries reported having
      regulations/procedures supporting the immunization of migrants at national level,
      one at sub-national level and three only targeting specific population groups.
      Eight countries offer migrant children all the vaccinations included in their
      national immunization schedule; three provide only selected vaccinations, mainly
      measles and polio vaccines. Ten and eight countries also offer selected
      vaccinations to adolescents and adults respectively. Eight countries provide
      vaccinations at the community level; seven give priority vaccines in holding
      centres or at entry sites. Data on administered vaccines are recorded in
      immunization registries in nine countries. Conclusions: Although differing among
      countries, indications for immunizing migrants are in place in most of them.
      However, we cannot infer from our findings whether those strategies are currently
      functioning and whether barriers to their implementation are being faced. Further
      studies focusing on these aspects are needed to develop concrete and targeted
      recommendations for action. Since migrants are moving across countries,
      development of on-line registries and cooperation between countries could allow
      keeping track of administered vaccines in order to appropriately plan
      immunization series and avoid unnecessary vaccinations.

PMID- 28441363
TI  - Mind-Body Therapy for Children with Attention-Deficit/Hyperactivity Disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is pervasive among the pediatric
      population and new treatments with minimal adverse effects are necessary to be
      studied. The purpose of this article is to review current research studying mind
      body therapies for treatment of children diagnosed with ADHD. Literature was
      reviewed pertaining to the effectiveness of movement-based therapies and
      mindfulness/meditation-based therapies for ADHD. Many positive effects of yoga,
      Tai Chi, physical activity, and meditation may significantly improve symptoms of
      ADHD among children.

PMID- 28441362
TI  - Real-World Experiences with the Combination Treatment of Ledipasvir plus
      Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement
      of a Sustained Virological Response in Previous Users of Peginterferon plus
      Ribavirin with HCV NS3/4A Inhibitors.
AB  - The aim of this study was to characterize the treatment response and serious
      adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients
      infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study
      analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of
      ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12
      weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among
      treatment-naive patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and
      among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%)
      patients. In patients previously treated with peginterferon plus ribavirin with
      various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two
      relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B
      S282 was observed after they relapsed. We experienced two patients with cardiac
      events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir
      for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for
      HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse
      events.

PMID- 28441364
TI  - Indole Derivatives Produced by the Metagenome Genes of the Escherichia coli
      Harboring Marine Sponge Discodermia calyx.
AB  - Three indole derivatives, a novel benzoxazine-indole hybrid (1) and two known
      indole trimers (2, 3), were isolated from the metagenomic library of the marine
      sponge Discodermia calyx based on functional screening. Their structures were
      elucidated by extensive spectroscopic analysis and comparison of their NMR data
      to that of known compounds. The antibacterial assay indicated that only compound
      2 displayed significant antibacterial activity against Bacillus cereus, with
      approximately 20 mm diameter growth inhibition at 10 ug/paper. HPLC analyses
      revealed that compound 2 is a newly induced metabolite, and the concentration of
      3 was obviously enhanced in contrast to negative control, while 1 was not
      detected, allowing us to predict that the formation of 2 might be induced by
      exogenous genes derived from the sponge metagenome, whereas compound 1 could be
      formed through a non-enzymatic process during the isolation procedure.

PMID- 28441365
TI  - Efficacy and Safety of 3 Nasal Packing Materials Used After Functional Endoscopic
      Sinus Surgery for Chronic Rhinosinusitis: A Comparative Study in China.
AB  - BACKGROUND This study aimed to investigate the efficacy and safety of 3 nasal
      packing products (silicone tube, Beschitin-F, and Aquacel1-Ag) after functional
      endoscopic sinus surgery (FESS) for chronic rhinosinusitis (CRS) patients in
      China. MATERIAL AND METHODS Sixty-six CRS patients undergoing FESS surgery were
      randomly divided into 3 groups (22 patients in each group): the silicone tube
      group, the Beschitin-F group, and the Aquacel1-Ag group. Postoperative headache,
      nasal pain, nasal bleeding, and swelling of the nasal mucosa were observed at 1
      month after FESS surgery. Bacteriology of chronic rhinosinusitis was conducted by
      culturing the removed nasal packing. RESULTS The VAS scores of nasal pain in the
      silicone tube group were lower than in the Beschitin-F and the Aquacel1-Ag
      groups. The volume of nasal bleeding in the Beschitin-F group was higher than in
      the silicone tube and Aquacel1-Ag groups. The adhesion rate of the nasal cavity
      in the Beschitin-F1 group (2/22, 9.1%) was also higher than in the silicone tube
      group (0/22, 0%) and the Aquacel1-Ag group (0/22, 0%). The results of bacterial
      culture from removed nasal packing showed that coagulase-negative staphylococci
      (CNS) was more frequent in the silicone tube group than in the Beschitin-F and
      Aquacel1-Ag groups, but Streptococcus pneumonia, Haemophilus influenza, and Gram
      negative rods were more common in the Aquacel1-Ag group than in the silicone tube
      and Beschitin-F groups. CONCLUSIONS These results indicate that the silicone tube
      may be more effective and safe than Beschitin-F and Aquacel1-Ag as nasal packing
      after FES surgery for CRS.

PMID- 28441366
TI  - Time Spent by Breast Imaging Radiologists to Perform Value-Added Activities at an
      Academic Cancer Center.
AB  - BACKGROUND: Health care reform in the United States has generated a paradigm
      shift in the practice of radiology aimed at increasing the degree of patient
      centered care. We conducted a study to quantify the amount of time breast imaging
      radiologists spend on value-added activities at an academic comprehensive cancer
      center located in Miami, Florida, and accredited by the American College of
      Radiology as a Breast Imaging Center of Excellence. METHODS: A prospective,
      observational study was conducted during a period of 20 consecutive workdays.
      Three participating breast imaging radiologists maintained a real-time log of
      each activity performed. A generalized linear model was used to perform a 1-way
      analysis of variance. An alpha level of .05 was used to determine statistical
      significance. RESULTS: The average daily time dedicated to these activities was
      92.1 minutes (range, 56.4-132.2). The amount of time significantly differed among
      breast imaging radiologists and correlated with their assigned daily role (P <
      .001 for both) but was independent of their years of experience. The daily role
      that required the most time was the interpretation of diagnostic imaging studies,
      which is when most interactions with patients, their relatives, and referring
      physicians occurred. The specific activity that required the most time was
      preparing for and participating in tumor boards. CONCLUSIONS: Our findings
      suggest that the breast imaging radiologists who participated in this study
      dedicated a significant amount of their time to value-added activities to help
      improve patients' experience across the continuity of their care. We propose that
      similar studies be conducted at other institutions to better assess the magnitude
      of this finding across different breast imaging care settings.

PMID- 28441367
TI  - Imaging Management of Breast Density, a Controversial Risk Factor for Breast
      Cancer.
AB  - BACKGROUND: Breast density is well recognized as an independent risk factor for
      the development of breast cancer. However, the magnitude of risk is
      controversial. As the public becomes increasingly aware of breast density as a
      risk factor, legislation and notification laws in relation to breast density have
      become common throughout the United States. Awareness of breast density as a risk
      factor for breast cancer presents new challenges for the clinician in the
      approach to the management and screening of women with dense breasts. METHODS:
      The evidence and controversy surrounding breast density as a risk factor for the
      development of breast cancer are discussed. Common supplemental screening
      modalities for breast cancer are also discussed, including tomosynthesis,
      ultrasonography, and magnetic resonance imaging. A management strategy for
      screening women with dense breasts is also presented. RESULTS: The American
      College of Radiology recognizes breast density as a controversial risk factor for
      breast cancer, whereas the American Congress of Obstetricians and Gynecologists
      recognizes breast density as a modest risk factor. Neither organization
      recommends the routine use of supplemental screening in women with dense breasts
      without considering additional patient-related risk factors. CONCLUSIONS: Breast
      density is a poorly understood and controversial risk factor for the development
      of breast cancer. Mammography is a screening modality proven to reduce breast
      cancer-related mortality rates and is the single most appropriate tool for
      population-based screening. Use of supplemental screening modalities should be
      tailored to individual risk assessment.

PMID- 28441368
TI  - Skeletal Scintigraphy.
AB  - BACKGROUND: Skeletal scintigraphy remains a valuable tool in the initial and
      subsequent evaluation of the skeletal system in patients with a diagnosis of
      primary or metastatic neoplasms. METHODS: We discuss radiopharmaceuticals,
      nuclear medicine imaging techniques, and current as well as future oncological
      applications in the adult population. Pertinent literature was reviewed to
      describe the advantages and limitations of available technologies for the
      evaluation of skeletal metastatic disease. Evaluation of primary and metastatic
      skeletal disease using nuclear medicine and positron emission tomography
      techniques is discussed. RESULTS: Skeletal scintigraphy provides valuable
      information in the initial evaluation for the presence of osteoblastic skeletal
      metastases. Incremental advances on available radiopharmaceuticals
      (fludeoxyglucose F 18, sodium fluoride F 18), coupled with advances in imaging
      techniques and imaging devices (single photon emission computed
      tomography/computed tomography, positron emission tomography/computed tomography,
      positron emission tomography/magnetic resonance imaging), have had a significant
      impact on sensitivity, specificity, and accuracy rates for the detection of
      skeletal metastases. CONCLUSIONS: Skeletal scintigraphy has a significant role in
      the initial diagnosis, staging, restaging, and treatment monitoring of patients
      with cancer and primary skeletal or metastatic disease. The coupling of
      diagnostic and therapeutic nuclear medicine agents in the setting of osteoblastic
      skeletal metastases is a valuable tool for the treatment for certain cancer
      types, including prostate cancer, and may become more widely used to treat other
      histologies as more data on other tumor types (eg, breast cancer, osteosarcoma)
      become available.

PMID- 28441369
TI  - Cardiac Magnetic Resonance Imaging in Oncology.
AB  - BACKGROUND: Cardiac magnetic resonance imaging (MRI) is emerging as an important
      diagnostic modality in the management of cardiovascular-related dysfunction in
      oncological diseases. Advances in imaging techniques have enhanced the detection
      and evaluation of cardiac masses; meanwhile, innovative applications have created
      a growing role for cardiac MRI for the management of cardiotoxicity caused by
      cancer therapies. METHODS: An overview is provided of the clinical indications
      and technical considerations of cardiac MRI. Its role in the evaluation of
      cardiac masses and cardiac function is reviewed, and novel sequences are
      discussed that are giving rise to future directions in cardio-oncology research.
      A review of the literature was also performed, focusing on cardiac MRI findings
      associated with cardiac dysfunction related to cancer treatment. RESULTS: Cardiac
      MRI can be used to differentiate benign and malignant primary cardiac tumors,
      metastatic disease, and pseudotumors with high spatial and temporal resolution.
      Cardiac MRI can also be used to detect the early and long-term effects of
      cardiotoxicity related to cancer therapy. This is accomplished through a
      multiparametric approach that uses conventional bright blood, dark blood, and
      postcontrast sequences while also considering the applicability of newer T1 and
      T2 mapping sequences and other emerging techniques. CONCLUSIONS: Cardio-oncology
      programs have an expanding presence in the multidisciplinary approach of cancer
      care. Consequently, knowledge of cardiac MRI and its potential applications is
      critical to the success of contemporary cancer diagnostics and cancer management.

PMID- 28441370
TI  - Conventional Modalities and Novel, Emerging Imaging Techniques for
      Musculoskeletal Tumors.
AB  - BACKGROUND: Imaging of musculoskeletal tumors requires a multimodality approach
      and includes radiography, computed tomography (CT), and magnetic resonance
      imaging (MRI). METHODS: Topics related to primary bone and soft-tissue tumors are
      reviewed. The fundamental imaging principles are discussed as well as the
      applications of emerging imaging modalities. RESULTS: MRI is the preferred
      technique for the evaluation of musculoskeletal tumors, whereas other imaging
      modalities play a complementary role. Radiography is indicated as the first-line
      imaging modality in bone and soft-tissue tumors, whereas CT is the preferred
      modality for evaluating cortical osseous lesions or calcifications and in
      patients with contraindications to MRI. Positron emission tomography (PET)/CT and
      PET/MRI are helpful in identifying the glucose metabolism of the lesion.
      Ultrasonography is the most useful for biopsy guidance and can aid in
      differentiating cystic from solid masses and identifying vascularity. Novel
      modalities, such as diffusion-weighted imaging, spectroscopy, and habitat
      imaging, show promise in increasing diagnostic accuracy and affecting treatment
      strategies. CONCLUSIONS: Conventional modalities and emerging, novel imaging
      techniques can provide noninvasive methods to diagnose and evaluate
      musculoskeletal tumors.

PMID- 28441372
TI  - Assessing Response of High-Grade Gliomas to Immune Checkpoint Inhibitors.
AB  - BACKGROUND: Immunotherapeutic agents, especially checkpoint inhibitors, have
      emerged as the mainstay of therapy for several solid and hematological
      malignancies. These therapies are under investigation for the treatment of high
      grade gliomas and brain metastases. METHODS: This article reviews the unique
      challenges encountered when evaluating changes on magnetic resonance imaging
      (MRI) of glioblastomas seen in response to immunotherapy and checkpoint
      inhibitors and how to effectively incorporate MRI findings into the response
      assessment of high-grade gliomas to these emerging therapies. RESULTS: An
      increase in tumor size or the appearance of new lesions on MRI may represent
      either an immune-mediated inflammatory response or true tumor progression, which
      may precede the subsequent stabilization or response of high-grade gliomas to
      immunotherapy. These MRI findings should not result in the mandatory cessation of
      immunotherapy in patients with high-grade glioma. CONCLUSIONS: Although
      immunotherapy Response Assessment for Neuro-Oncology criteria have been developed
      to assist with response assessment of high-grade gliomas to immunotherapy and to
      provide guidance with treatment decisions, these criteria have not been validated
      in prospective clinical trials. In patients with brain tumors who are receiving
      immunotherapy, MRI findings suggestive of disease progression should be evaluated
      with caution to prevent premature discontinuation of potentially beneficial
      therapies. Close, clinical monitoring with appropriate short-term, follow-up
      imaging is often necessary, and histopathological analysis may be required in
      some cases to confirm disease progression before a decision on continuation of
      these novel therapies can accurately be made.

PMID- 28441371
TI  - Multimodal Imaging of Head and Neck Squamous Cell Carcinoma.
AB  - BACKGROUND: The role of imaging in the staging, treatment planning, and ongoing
      surveillance of patients with head and neck squamous cell carcinoma (HNSCC)
      continues to evolve. Changes in patient demographics, treatment paradigms, and
      technology present opportunities and challenges for the management of HNSCC.
      METHODS: The general indications and usage of standard and multimodal cross
      sectional imaging in the evaluation and management of HNSCC are reviewed, with an
      emphasis on incorporating them into treatment pathways. Emerging imaging
      technologies and methods with a potential near-term impact on HNSCC are
      discussed. RESULTS: In general, the complex, multidisciplinary approach to the
      treatment of advanced HNSCC requires multimodal imaging for adequate treatment
      planning and follow up. Early-stage disease can often be managed with clinical
      and endoscopic examinations and a single, cross-sectional imaging modality (eg,
      computed tomography, magnetic resonance imaging). CONCLUSIONS: Although
      generalized treatment pathways and guidelines do exist, the literature is rapidly
      advancing and new radiotracers and evaluation methods are expected to alter both
      imaging and treatment recommendations in the years to come.

PMID- 28441373
TI  - Cost-Effectiveness Analysis of Interventions to Reduce Risk of Aspiration in
      Elderly Cancer Survivors Residing in Skilled Nursing Facilities.
AB  - BACKGROUND: Aspiration can occur in patients of any age group, but it can be
      prevented. The primary population at risk is made up of survivors of cancer
      because of their increased risk of mucositis, mucosal atrophy, and dysphagia
      associated with chemotherapy, radiotherapy, and the disease process itself. The
      rate of incidence of aspiration cannot be quantified, because minor cases of
      aspiration often go unreported. Sequelae ensuing from aspirations can include
      pneumonia, end-stage kidney disease, dialysis, and death. METHODS: Analyses of
      cost, decision-tree modeling, and cost effectiveness were performed to compare a
      hypothetical, interventional model based on best practices with usual (standard)
      care. A societal perspective was used as the economic view point. Direct costs,
      caregiver time, and market values for wages were estimated for the 2
      interventions. Effectiveness values for the cost-effectiveness and decision-tree
      analyses were obtained from the literature. The incremental-cost-effectiveness
      ratio was calculated and used to compare the intervention with usual care.
      RESULTS: The interventional method was more costly but more effective than usual
      care. A sensitivity analysis considered the uncertainty of event probability
      (aspiration vs no aspiration). The interventional protocol for aspiration
      reduction continued to be more cost effective than usual care. CONCLUSIONS:
      Aspiration takes a financial toll on all facets of health care, including on
      nurses, skilled nursing facilities, patients, their families, and insurers, among
      others. Implementing guidelines that describe best practices for aspiration
      appears to be a cost-effective strategy for reducing aspirations among cancer
      survivors - especially elderly patients - who live in skilled nursing facilities.

PMID- 28441374
TI  - Fever in Patients With Cancer.
AB  - BACKGROUND: The definition of fever is flexible and depends on the clinical
      context. Fever is frequently observed in patients with cancer. METHODS:
      Infectious and noninfectious causes of fever in patients with various oncological
      and hematological malignancies and the usefulness of biomarkers are discussed.
      RESULTS: To treat patients in a timely manner and to minimize morbidity and
      mortality, it is paramount that health care professionals determine the cause of
      fever. The usefulness of biomarkers in febrile patients with cancer continues to
      be controversial. CONCLUSIONS: Fever is frequently seen in patients with cancer
      and can be associated with a variety of infectious and noninfectious causes. The
      utility of acute-phase reactants, such as erythrocyte sedimentation rate, C
      reactive protein, and procalcitonin, along with a nonsteroidal anti-inflammatory
      drug challenge should be further evaluated as adjunct tools for the workup of
      fever in patients with cancer.

PMID- 28441375
TI  - Primary Adrenal Angiosarcoma: A Rare and Potentially Misdiagnosed Tumor.
AB  - A man aged 69 years presented with acute right flank pain secondary to a
      hemorrhagic large adrenal tumor. En bloc resection was performed to repair the
      inferior vena cava. Immunoperoxidase levels in the tumor were positive for factor
      VIII and CD31 and negative for S100, protein Melan-A, CD34, synaptophysin,
      chromogranin, desmin, muscle specific actin, ETFA (EMA), KRT20 (CK20), CDX2,
      TTF1, LNPEP (PLAP), inhibin, ?-fetoprotein, CD30, hepatocyte paraffin, and
      aberrant expression of cytokeratin 7 and pankeratin. The pathological diagnosis
      was consistent with adrenal angiosarcoma. Obtaining appropriate immunoperoxidase
      stains and multidisciplinary evaluation helped make the diagnosis of this rare
      adrenal tumor and determine its management. The patient had an uneventful
      postoperative course and completed 4 cycles of adjuvant chemotherapy with
      doxorubicin/ifosfamide and adequately tolerated the treatment. However, positive
      surgical margins were found, so he was referred to radiation oncology specialists
      for possible adjuvant radiotherapy to the surgical bed. Weeks after the first
      initiation of therapy, the patient presented to the emergency department
      complaining of shortness of breath, fatigue, and generalized weakness for 3 days.
      He was admitted and found to have new-onset anemia and a new-onset, large, right
      pleural effusion. Thoracentesis performed showed sanguinolent fluid that, after
      microscopic evaluation, was suggestive of recurrent malignancy. Thoracic
      aortography performed with subselective catheterization to several arteries
      (right bronchial, right phrenic, and right renal arteries) did not show any
      active bleeding. However, the right inferior intercostal and adrenal arteries
      were presumed to be the reason for the bleeding event, so they were embolized
      until stasis. The patient remained hemodynamically unstable but eventually
      experienced multiorgan failure. In spite of aggressive measures, he died 10 days
      after admission to the hospital.

PMID- 28441376
TI  - NUT Midline Carcinoma: A Rare Malignancy.
AB  - Nuclear protein of the testis (NUT) midline carcinoma can present in the head,
      neck, and mediastinum. In general, it presents in young adult men and has a poor
      prognosis. We report on a case of NUT midline carcinoma of the mediastinum in a
      man 27 years of age without any prior malignancy. Due to the location of the
      tumor, mediastinal lymphoma and germ cell tumor were initially considered;
      however, immunohistochemistry was performed using NUT antibody that revealed it
      to be NUT midline carcinoma. Although guidelines exist for squamous cell
      carcinoma of the head, neck, and mediastinum, no such specific guidelines are
      available for NUT midline carcinoma, which looks morphologically similar to
      squamous cell carcinoma but behaves more aggressively and carries a poor
      prognosis.

PMID- 28441377
TI  - CD4-Positive T-Cell Large Granular Lymphocytosis Mimicking Sezary Syndrome in a
      Patient With Mycosis Fungoides.
AB  - A white woman aged 65 years presented with a macular, nonscaly, nonpruritic,
      erythematous lesion on her right breast. Test results revealed histological
      features similar to lichenoid dermatitis and early-phase primary cutaneous T-cell
      lymphoma with a subtype of mycosis fungoides (MF). Despite topical therapy with
      steroids, her skin disease continued to progress, so she underwent polymerase
      chain reaction and gene mutation testing. Two missense mutations were detected.
      The overall findings supported a diagnosis of co-occurring, CD4-positive large
      granular lymphocytosis and stage IA MF. The patient continued to receive topical
      steroids and maintenance phototherapy, and her skin lesions completely resolved
      after 14 weeks of therapy. Approximately 5 years after her initial presentation,
      she was free of symptoms, cytopenia, and no skin lesions were present. CD4
      positive, large granular lymphocytosis was persistent. This patient case - to our
      knowledge, the first of its kind - posed dilemmas of a diagnostic and therapeutic
      nature. Correctly staging the lymphoma helped to aid the diagnosis and can help
      prevent patients similar to the one in this case from receiving unnecessary
      therapy.

PMID- 28441378
TI  - Innovations in Diagnostic Imaging and the Transformation of the Clinical Practice
      of Radiology in Collaborative, Multidisciplinary Cancer Care.

PMID- 28441379
TI  - Finally, a Practical Approach to Value-Based Medicine.

PMID- 28441380
TI  - Comparison of general obesity and measures of body fat distribution in older
      adults in relation to cancer risk: meta-analysis of individual participant data
      of seven prospective cohorts in Europe.
AB  - BACKGROUND: We evaluated the associations of anthropometric indicators of general
      obesity (body mass index, BMI), an established risk factor of various cancer, and
      body fat distribution (waist circumference, WC; hip circumference, HC; and waist
      to-hip ratio, WHR), which may better reflect metabolic complications of obesity,
      with total obesity-related and site-specific (colorectal and postmenopausal
      breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective
      cohort studies participating in the CHANCES consortium including 18 668 men and
      24 751 women with a mean age of 62 and 63 years, respectively. Harmonised
      individual participant data from all seven cohorts were analysed separately and
      alternatively for each anthropometric indicator using multivariable Cox
      proportional hazards models. RESULTS: After a median follow-up period of 12
      years, 1656 first-incident obesity-related cancers (defined as postmenopausal
      female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder,
      pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the
      meta-analysis of all studies, associations between indicators of adiposity, per
      s.d. increment, and risk for all obesity-related cancers combined yielded the
      following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI
      1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32)
      for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%,
      respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone
      therapy (HT) use was observed for postmenopausal breast cancer
      (Pinteraction<0.001), where never HT users showed an ~20% increased risk per s.d.
      of BMI, WC, and HC compared to ever users. CONCLUSIONS: BMI, WC, HC, and WHR show
      comparable positive associations with obesity-related cancers combined and with
      colorectal cancer in older adults. For postmenopausal breast cancer we report
      evidence for effect modification by HT use.

PMID- 28441381
TI  - Text-message Reminders in Colorectal Cancer Screening (TRICCS): a randomised
      controlled trial.
AB  - BACKGROUND: We investigated the effectiveness of a text-message reminder to
      improve uptake of the English Bowel Cancer Screening programme in London.
      METHODS: We performed a randomised controlled trial across 141 general practices
      in London. Eight thousand two hundred sixty-nine screening-eligible adults (aged
      60-74 years) were randomised in a 1 : 1 ratio to receive either a text-message
      reminder (n=4134) or no text-message reminder (n=4135) if they had not returned
      their faecal occult blood test kit within 8 weeks of initial invitation. The
      primary outcome was the proportion of adults returning a test kit at the end of
      an 18-week screening episode (intention-to-treat analysis). A subgroup analysis
      was conducted for individuals receiving an invitation for the first time.
      RESULTS: Uptake was 39.9% in the control group and 40.5% in the intervention
      group. Uptake did not differ significantly between groups for the whole study
      population of older adults (adjusted odds ratio (OR) 1.03, 95% confidence
      interval (CI) 0.94-1.12; P=0.56) but did vary between the groups for first-time
      invitees (uptake was 34.9% in the control and 40.5% in the intervention; adjusted
      OR 1.29, 95% CI 1.04-1.58; P=0.02). CONCLUSIONS: Although text-message reminders
      did not significantly increase uptake of the overall population, the improvement
      among first-time invitees is encouraging.

PMID- 28441382
TI  - Hedgehog signalling pathway orchestrates angiogenesis in triple-negative breast
      cancers.
AB  - BACKGROUND: Several evidences suggest a marked angiogenic dependency in triple
      negative breast cancer (TNBC) tumorigenesis and a potential sensitivity to anti
      angiogenic agents. Herein, the putative role of Hedgehog (Hh) pathway in
      regulating TNBC-dependent angiogenesis was investigated. METHODS: Expression and
      regulation of the Hh pathway transcription factor glioma-associated oncogene
      homolog1 protein (GLI1) were studied on the endothelial compartment and on TNBC
      initiated angiogenesis. To evaluate the translational relevance of our findings,
      the combination of paclitaxel with the Smo inhibitor NVP-LDE225 was tested in
      TNBC xenografted mice. RESULTS: Tissue microarray analysis on 200 TNBC patients
      showed GLI1 overexpression paired with vascular endothelial growth factor
      receptor 2 (VEGFR2) expression. In vitro, Hh pathway promotes TNBC progression in
      an autocrine manner, regulating the VEGF/VEGFR2 loop on cancer cell surface, and
      in a paracrine manner, orchestrating tumour vascularisation. These effects were
      counteracted by Smo pharmacological inhibition. In TNBC xenografted mice,
      scheduling NVP-LDE225 rather than bevacizumab provided a better sustained
      inhibition of TNBC cells proliferation and endothelial cells organisation.
      CONCLUSIONS: This study identifies the Hh pathway as one of the main regulators
      of tumour angiogenesis in TNBC, thus suggesting Hh inhibition as a potential new
      anti-angiogenic therapeutic option to be clinically investigated in GLI1
      overexpressing TNBC patients.

PMID- 28441383
TI  - The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with
      the MEK inhibitor trametinib in advanced cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited
      therapeutic options. MEK inhibition and antiangiogenic therapies have
      individually shown modest activity in advanced cholangiocarcinoma, whereas dual
      inhibition of these pathways has not been previously evaluated. We evaluated the
      safety and efficacy of combination therapy with the oral VEGF receptor tyrosine
      kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with
      advanced cholangiocarcinoma. METHODS: In this open-label, multicentre, single-arm
      trial, adults with advanced unresectable cholangiocarcinoma received pazopanib
      800 mg daily and trametinib 2 mg daily until disease progression or unacceptable
      toxicity. The primary end point was progression-free survival (PFS) with
      secondary end points including overall survival (OS), response rate, and disease
      control rate (DCR). RESULTS: A total of 25 patients were enrolled and had
      received a median of 2 prior systemic therapies (range 1-7). Median PFS was 3.6
      months (95% CI: 2.7-5.1) and the 4-month PFS was 40% (95% CI: 24.7-64.6%). There
      was a trend towards increased 4-month PFS as compared with the prespecified null
      hypothesised 4-month PFS of 25%, but this difference did not reach statistical
      significance (P=0.063). The median survival was 6.4 months (95% CI: 4.3-10.2).
      The objective response rate was 5% (95% CI: 0.13-24.9%) and the DCR was 75% (95%
      CI: 51%, 91%). Grade 3/4 adverse events attributable to study drugs were observed
      in 14 (56%) and included thrombocytopenia, abnormal liver enzymes, rash, and
      hypertension. CONCLUSIONS: Although the combination of pazopanib plus trametinib
      had acceptable toxicity with evidence of clinical activity, it did not achieve a
      statistically significant improvement in 4-month PFS over the prespecified null
      hypothesised 4-month PFS.

PMID- 28441384
TI  - Hopefully devoted to Q: targeting glutamine addiction in cancer.
AB  - Altered cell metabolism enables tumours to sustain their increased energetic and
      biosynthetic needs. Although tumour metabolism has long been considered a
      promising discipline in the development of cancer therapeutics, the majority of
      work has focused on changes in glucose metabolism. However, the complexity of
      cellular metabolism means that very rarely is an individual metabolite required
      for a single purpose, and thus understanding the overall metabolic requirements
      of tumours is vital. Over the past 30 years, increasing evidence has shown that
      many tumours require glutamine as well as glucose for their proliferation and
      survival. In this minireview, we explore the complexity of glutamine metabolism
      in tumour cells, discussing how the overall context of the tumour dictates the
      requirement for glutamine and how this can affect the design of effective
      therapeutic strategies.

PMID- 28441385
TI  - Preoperative clinical pathway of breast cancer patients: determinants of
      compliance with EUSOMA quality indicators.
AB  - BACKGROUND: The European Society of Breast Cancer Specialists (EUSOMA) has
      defined quality indicators for breast cancer (BC). The aim of this study was to
      describe the preoperative clinical pathway of breast cancer patients and evaluate
      the determinants of compliance with EUSOMA quality indicators in the Optisoins01
      cohort. METHODS: Optisoins01 is a prospective, multicentric study. Data from
      operable BC patients were collected, including results from before surgery to 1
      year follow-up. Seven preoperative EUSOMA quality indicators were compared with
      the clinical pathways Optisoins01. RESULTS: Six hundred and four patients were
      included. European Society of Breast Cancer Specialists targets were reached for
      indicator 1 (completeness of clinical and imaging diagnostic work-up), 3
      (preoperative definitive diagnosis) and 5 (waiting time). For indicator 8
      (multidisciplinary discussion), the minimum standard of 90% of the patients was
      reached only in general hospitals and comprehensive cancer centres. Having more
      than 1 medical examination within the centre was associated with an increased
      waiting time for surgery, whereas it was reduced by having an outpatient breast
      biopsy. The comprehensive cancer centre type was the only parameter associated
      with the other quality indicators. CONCLUSIONS: European Society of Breast Cancer
      Specialists quality indicators are a useful tool to evaluate care organisations.
      This study highlights the need for a standardised and coordinated preoperative
      clinical pathway.

PMID- 28441386
TI  - Graft-derived cell-free DNA, a noninvasive early rejection and graft damage
      marker in liver transplantation: A prospective, observational, multicenter cohort
      study.
AB  - BACKGROUND: Graft-derived cell-free DNA (GcfDNA), which is released into the
      blood stream by necrotic and apoptotic cells, is a promising noninvasive organ
      integrity biomarker. In liver transplantation (LTx), neither conventional liver
      function tests (LTFs) nor immunosuppressive drug monitoring are very effective
      for rejection monitoring. We therefore hypothesized that the quantitative
      measurement of donor-derived cell-free DNA (cfDNA) would have independent value
      for the assessment of graft integrity, including damage from acute rejection.
      METHODS AND FINDINGS: Traditional LFTs were performed and plasma GcfDNA was
      monitored in 115 adults post-LTx at three German transplant centers as part of a
      prospective, observational, multicenter cohort trial. GcfDNA percentage (graft
      cfDNA/total cfDNA) was measured using droplet digital PCR (ddPCR), based on a
      limited number of predefined single nucleotide polymorphisms, enabling same-day
      turn-around. The same method was used to quantify blood microchimerism. GcfDNA
      was increased >50% on day 1 post-LTx, presumably from ischemia/reperfusion
      damage, but rapidly declined in patients without graft injury within 7 to 10 d to
      a median <10%, where it remained for the 1-y observation period. Of 115 patients,
      107 provided samples that met preestablished criteria. In 31 samples taken from
      17 patients during biopsy-proven acute rejection episodes, the percentage of
      GcfDNA was elevated substantially (median 29.6%, 95% CI 23.6%-41.0%) compared
      with that in 282 samples from 88 patients during stable periods (median 3.3%, 95%
      CI 2.9%-3.7%; p < 0.001). Only slightly higher values (median 5.9%, 95% CI 4.4%
      10.3%) were found in 68 samples from 17 hepatitis C virus (HCV)-positive,
      rejection-free patients. LFTs had low overall correlations (r = 0.28-0.62) with
      GcfDNA and showed greater overlap between patient subgroups, especially between
      acute rejection and HCV+ patients. Multivariable logistic regression modeling
      demonstrated that GcfDNA provided additional LFT-independent information on graft
      integrity. Diagnostic sensitivity and specificity were 90.3% (95% CI 74.2%-98.0%)
      and 92.9% (95% CI 89.3%-95.6%), respectively, for GcfDNA at a threshold value of
      10%. The area under the receiver operator characteristic curve was higher for
      GcfDNA (97.1%, 95% CI 93.4%-100%) than for same-day conventional LFTs (AST:
      95.7%; ALT: 95.2%; gamma-GT: 94.5%; bilirubin: 82.6%). An evaluation of
      microchimerism revealed that the maximum donor DNA in circulating white blood
      cells was only 0.068%. GcfDNA percentage can be influenced by major changes in
      host cfDNA (e.g., due to leukopenia or leukocytosis). One limitation of our study
      is that exact time-matched GcfDNA and LFT samples were not available for all
      patient visits. CONCLUSIONS: In this study, determination of GcfDNA in plasma by
      ddPCR allowed for earlier and more sensitive discrimination of acute rejection in
      LTx patients as compared with conventional LFTs. Potential blood microchimerism
      was quantitatively low and had no significant influence on GcfDNA value. Further
      research, which should ideally include protocol biopsies, will be needed to
      establish the practical value of GcfDNA measurements in the management of LTx
      patients.

PMID- 28441387
TI  - Governing multisectoral action for health in low- and middle-income countries.
AB  - Kumanan Rasanathan and colleagues argue that the potential of multisectoral
      collaboration for improving health remains untapped in many low- and middle
      income countries.

PMID- 28441388
TI  - A population-based approach for implementing change from opt-out to opt-in
      research permissions.
AB  - Due to recently proposed changes in the Common Rule regarding the collection of
      research preferences, there is an increased need for efficient methods to
      document opt-in research preferences at a population level. Previously, our
      institution developed an opt-out paper-based workflow that could not be utilized
      for research in a scalable fashion. This project was designed to demonstrate the
      feasibility of implementing an electronic health record (EHR)-based active opt-in
      research preferences program. The first phase of implementation required creating
      and disseminating a patient questionnaire through the EHR portal to populate
      discreet fields within the EHR indicating patients' preferences for future
      research study contact (contact) and their willingness to allow anonymised use of
      excess tissue and fluid specimens (biobank). In the second phase, the
      questionnaire was presented within a clinic nurse intake workflow in an
      obstetrical clinic. These permissions were tabulated in registries for use by
      investigators for feasibility studies and recruitment. The registry was also used
      for research patient contact management using a new EHR encounter type to
      differentiate research from clinical encounters. The research permissions
      questionnaire was sent to 59,670 patients via the EHR portal. Within four months,
      21,814 responses (75% willing to participate in biobanking, and 72% willing to be
      contacted for future research) were received. Each response was recorded within a
      patient portal encounter to enable longitudinal analysis of responses. We
      obtained a significantly lower positive response from the 264 females who
      completed the questionnaire in the obstetrical clinic (55% volunteers for biobank
      and 52% for contact). We demonstrate that it is possible to establish a research
      permissions registry using the EHR portal and clinic-based workflows. This
      patient-centric, population-based, opt-in approach documents preferences in the
      EHR, allowing linkage of these preferences to health record information.

PMID- 28441389
TI  - The basis of sharp spike onset in standard biophysical models.
AB  - In most vertebrate neurons, spikes initiate in the axonal initial segment (AIS).
      When recorded in the soma, they have a surprisingly sharp onset, as if sodium
      (Na) channels opened abruptly. The main view stipulates that spikes initiate in a
      conventional manner at the distal end of the AIS, then progressively sharpen as
      they backpropagate to the soma. We examined the biophysical models used to
      substantiate this view, and we found that spikes do not initiate through a local
      axonal current loop that propagates along the axon, but through a global current
      loop encompassing the AIS and soma, which forms an electrical dipole. Therefore,
      the phenomenon is not adequately modeled as the backpropagation of an electrical
      wave along the axon, since the wavelength would be as large as the entire system.
      Instead, in these models, we found that spike initiation rather follows the
      critical resistive coupling model proposed recently, where the Na current
      entering the AIS is matched by the axial resistive current flowing to the soma.
      Besides demonstrating it by examining the balance of currents at spike
      initiation, we show that the observed increase in spike sharpness along the axon
      is artifactual and disappears when an appropriate measure of rapidness is used;
      instead, somatic onset rapidness can be predicted from spike shape at initiation
      site. Finally, we reproduce the phenomenon in a two-compartment model, showing
      that it does not rely on propagation. In these models, the sharp onset of somatic
      spikes is therefore not an artifact of observing spikes at the incorrect
      location, but rather the signature that spikes are initiated through a global
      soma-AIS current loop forming an electrical dipole.

PMID- 28441390
TI  - Parameters-tuning of PID controller for automatic voltage regulators using the
      African buffalo optimization.
AB  - In this paper, an attempt is made to apply the African Buffalo Optimization (ABO)
      to tune the parameters of a PID controller for an effective Automatic Voltage
      Regulator (AVR). Existing metaheuristic tuning methods have been proven to be
      quite successful but there were observable areas that need improvements
      especially in terms of the system's gain overshoot and steady steady state
      errors. Using the ABO algorithm where each buffalo location in the herd is a
      candidate solution to the Proportional-Integral-Derivative parameters was very
      helpful in addressing these two areas of concern. The encouraging results
      obtained from the simulation of the PID Controller parameters-tuning using the
      ABO when compared with the performance of Genetic Algorithm PID (GA-PID),
      Particle-Swarm Optimization PID (PSO-PID), Ant Colony Optimization PID (ACO-PID),
      PID, Bacteria-Foraging Optimization PID (BFO-PID) etc makes ABO-PID a good
      addition to solving PID Controller tuning problems using metaheuristics.

PMID- 28441392
TI  - Radiation effects on the mixed convection flow induced by an inclined stretching
      cylinder with non-uniform heat source/sink.
AB  - This study investigates the mixed convection flow of Jeffrey liquid by an
      impermeable inclined stretching cylinder. Thermal radiation and non-uniform heat
      source/sink are considered. The convective boundary conditions at surface are
      imposed. Nonlinear expressions of momentum, energy and concentration are
      transformed into dimensionless systems. Convergent homotopic solutions of the
      governing systems are worked out by employing homotopic procedure. Impact of
      physical variables on the velocity, temperature and concentration distributions
      are sketched and discussed. Numerical computations for skin friction coefficient,
      local Nusselt and Sherwood numbers are carried out. It is concluded that velocity
      field enhances for Deborah number while reverse situation is observed regarding
      ratio of relaxation to retardation times. Temperature and heat transfer rate are
      enhanced via larger thermal Biot number. Effect of Schmidt number on the
      concentration and local Sherwood number is quite reverse.

PMID- 28441391
TI  - Apigenin inhibits TNFalpha/IL-1alpha-induced CCL2 release through IKBK-epsilon
      signaling in MDA-MB-231 human breast cancer cells.
AB  - Mortality associated with breast cancer is attributable to aggressive metastasis,
      to which TNFalpha plays a central orchestrating role. TNFalpha acts on breast
      tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP
      1/CCL2). These proteins direct inward infiltration/migration of tumor-associated
      macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived
      suppressor cells (MDSCs), T-regulatory cells (Tregs), T helper IL-17-producing
      cells (Th17s), metastasis-associated macrophages (MAMs) and cancer-associated
      fibroblasts (CAFs). Tumor embedded infiltrates collectively enable immune
      evasion, tumor growth, angiogenesis, and metastasis. In the current study, we
      investigate the potential of apigenin, a known anti-inflammatory constituent of
      parsley, to downregulate TNFalpha mediated release of chemokines from human
      triple-negative cells (MDA-MB-231 cells). The results show that TNFalpha
      stimulation leads to large rise of CCL2, granulocyte macrophage colony
      stimulating factor (GMCSF), IL-1alpha and IL-6, all suppressed by apigenin. While
      many aspects of the transcriptome for NFkB signaling were evaluated, the data
      show signaling patterns associated with CCL2 were blocked by apigenin and
      mediated through suppressed mRNA and protein synthesis of IKBKe. Moreover, the
      data show that the attenuation of CCL2 by apigenin in the presence TNFalpha
      paralleled the suppression of phosphorylated extracellular signal-regulated
      kinase 1 (ERK 1/ 2). In summary, the obtained findings suggest that there exists
      a TNFalpha evoked release of CCL2 and other LSP recruiting cytokines from human
      breast cancer cells, which can be attenuated by apigenin.

PMID- 28441393
TI  - Sequence learning modulates neural responses and oscillatory coupling in human
      and monkey auditory cortex.
AB  - Learning complex ordering relationships between sensory events in a sequence is
      fundamental for animal perception and human communication. While it is known that
      rhythmic sensory events can entrain brain oscillations at different frequencies,
      how learning and prior experience with sequencing relationships affect
      neocortical oscillations and neuronal responses is poorly understood. We used an
      implicit sequence learning paradigm (an "artificial grammar") in which humans and
      monkeys were exposed to sequences of nonsense words with regularities in the
      ordering relationships between the words. We then recorded neural responses
      directly from the auditory cortex in both species in response to novel legal
      sequences or ones violating specific ordering relationships. Neural oscillations
      in both monkeys and humans in response to the nonsense word sequences show
      strikingly similar hierarchically nested low-frequency phase and high-gamma
      amplitude coupling, establishing this form of oscillatory coupling-previously
      associated with speech processing in the human auditory cortex-as an
      evolutionarily conserved biological process. Moreover, learned ordering
      relationships modulate the observed form of neural oscillatory coupling in both
      species, with temporally distinct neural oscillatory effects that appear to
      coordinate neuronal responses in the monkeys. This study identifies the conserved
      auditory cortical neural signatures involved in monitoring learned sequencing
      operations, evident as modulations of transient coupling and neuronal responses
      to temporally structured sensory input.

PMID- 28441394
TI  - Maternal obese-type gut microbiota differentially impact cognition, anxiety and
      compulsive behavior in male and female offspring in mice.
AB  - Maternal obesity is known to predispose offspring to metabolic and
      neurodevelopmental abnormalities. While the mechanisms underlying these phenomena
      are unclear, high fat diets dramatically alter intestinal microbiota, and gut
      microbiota can impact physiological function. To determine if maternal diet
      induced gut dysbiosis can disrupt offspring neurobehavioral function, we
      transplanted high fat diet- (HFD) or control low fat diet-associated (CD) gut
      microbiota to conventionally-housed female mice. Recipient mice were then bred
      and the behavioral phenotype of male and female offspring was tracked. While
      maternal behavior was unaffected, neonatal offspring from HFD dams vocalized less
      upon maternal separation than pups from CD dams. Furthermore, weaned male
      offspring from HFD dams had significant and selective disruptions in exploratory,
      cognitive, and stereotypical/compulsive behavior compared to male offspring from
      CD dams; while female offspring from HFD dams had increases in body weight and
      adiposity. 16S metagenomic analyses confirmed establishment of divergent
      microbiota in CD and HFD dams, with alterations in diversity and taxonomic
      distribution throughout pregnancy and lactation. Likewise, significant
      alterations in gut microbial diversity and distribution were noted in offspring
      from HFD dams compared to CD dams, and in males compared to females. Regression
      analyses of behavioral performance against differentially represented taxa
      suggest that decreased representation of specific members of the Firmicutes
      phylum predict behavioral decline in male offspring. Collectively, these data
      establish that high fat diet-induced maternal dysbiosis is sufficient to disrupt
      behavioral function in murine offspring in a sex-specific manner. Thus these data
      reinforce the essential link between maternal diet and neurologic programming in
      offspring and suggest that intestinal dysbiosis could link unhealthy modern diets
      to the increased prevalence of neurodevelopmental and childhood disorders.

PMID- 28441395
TI  - Molecular phylogeny of Oncaeidae (Copepoda) using nuclear ribosomal internal
      transcribed spacer (ITS rDNA).
AB  - Copepods belonging to the Oncaeidae family are commonly and abundantly found in
      marine zooplankton. In the Mediterranean Sea, forty-seven oncaeid species occur,
      of which eleven in the Gulf of Naples. In this Gulf, several Oncaea species were
      morphologically analysed and described at the end of the XIX century by W.
      Giesbrecht. In the same area, oncaeids are being investigated over seasonal and
      inter-annual scales at the long-term coastal station LTER-MC. In the present
      work, we identified six oncaeid species using the nuclear ribosomal internal
      transcribed spacers (ITS rDNA) and the mitochondrial cytochrome c oxidase subunit
      I (mtCOI). Phylogenetic analyses based on these two genomic regions validated the
      sisterhood of the genera Triconia and the Oncaea sensu stricto. ITS1 and ITS2
      phylogenies produced incongruent results about the position of Oncaea curta,
      calling for further investigations on this species. We also characterised the
      ITS2 region by secondary structure predictions and found that all the sequences
      analysed presented the distinct eukaryotic hallmarks. A Compensatory Base Change
      search corroborated the close relationship between O. venusta and O. curta and
      between O. media and O. venusta already identified by ITS phylogenies. The
      present results, which stem from the integration of molecular and morphological
      taxonomy, represent an encouraging step towards an improved knowledge of copepod
      biodiversity: The two complementary approaches, when applied to long-term copepod
      monitoring, will also help to better understanding their genetic variations and
      ecological niches of co-occurring species.

PMID- 28441396
TI  - Prognostic significance of neutrophil-to-lymphocyte ratio in diffuse large B-cell
      lymphoma: A meta-analysis.
AB  - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been investigated as a
      prognostic marker in patients with diffuse large B-cell lymphoma (DLBCL);
      however, the results remain controversial. This study aimed to explore the
      association between NLR and survival outcomes and clinicopathological factors in
      DLBCL. METHODS: Relevant studies were retrieved by searching PubMed, Embase, Web
      of Science, and China National Knowledge Infrastructure (CNKI) databases. The
      last search was updated on February 17, 2017. Hazard ratios (HRs) and odds ratios
      (ORs) and their 95% confidence intervals (CIs) were used as effective measures in
      the meta-analysis. Random-effects models and fixed-effects models were used for
      analyses. Meta-regression was performed. Publication bias was assessed using
      Begg's test. Stata version 12.0 was used for all analyses. RESULTS: A total of 9
      studies with 2297 patients were included in the meta-analysis. The pooled results
      showed that NLR was a significant indicator for poor overall survival (OS) (HR =
      1.84, 95% CI = 1.52-2.22, p<0.001) and poor progression-free survival (PFS) (HR =
      1.64, 95% CI = 1.36-1.98, p<0.001). NLR remained a significant biomarker for OS
      and PFS regardless of location, sample size or cut-off value. In addition, high
      NLR was also associated with Ann Arbor stage (OR = 2.09, 95% CI = 1.14-3.81, p =
      0.017), lactate dehydrogenase level (OR = 2.74, 95% CI = 1.16-6.46, p = 0.021),
      extranodal disease (OR = 1.63, 95% CI = 1.06-2.52, p = 0.027), and International
      Prognostic Index score (OR = 2.44, 95% CI = 1.03-5.08, p = 0.043). However, NLR
      was found to have no significant association with sex (OR = 0.89, 95% CI = 0.71
      1.11, p = 0.29), age (OR = 1.18, 95% CI = 0.94-1.48, p = 0.152), European
      Cooperative Oncology Group performance status score (OR = 1.78, 95% CI = 0.71
      4.46, p = 0.217), or presence of B symptoms (OR = 1.56, 95% CI = 0.7-3.48, p =
      0.278). CONCLUSION: In conclusion, our meta-analysis demonstrated that NLR has a
      strong association with worse OS and PFS in patients with DLBCL. NLR could be
      recommended as an inexpensive prognostic biomarker in DLBCL.

PMID- 28441397
TI  - Correction: Functional Constraint Profiling of a Viral Protein Reveals
      Discordance of Evolutionary Conservation and Functionality.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1005310.].

PMID- 28441399
TI  - GHGs and air pollutants embodied in China's international trade: Temporal and
      spatial index decomposition analysis.
AB  - Temporal index decomposition analysis and spatial index decomposition analysis
      were applied to understand the driving forces of the emissions embodied in
      China's exports and net exports during 2002-2011, respectively. The accumulated
      emissions embodied in exports accounted for approximately 30% of the total
      emissions in China; although the contribution of the sectoral total emissions
      intensity (technique effect) declined, the scale effect was largely responsible
      for the mounting emissions associated with export, and the composition effect
      played a largely insignificant role. Calculations of the emissions embodied in
      net exports suggest that China is generally in an environmentally inferior
      position compared with its major trade partners. The differences in the economy
      wide emission intensities between China and its major trade partners were the
      biggest contribution to this reality, and the trade balance effect played a less
      important role. However, a lower degree of specialization in pollution intensive
      products in exports than in imports helped to reduce slightly the emissions
      embodied in net exports. The temporal index decomposition analysis results
      suggest that China should take effective measures to optimize export and supply
      side structure and reduce the total emissions intensity. According to spatial
      index decomposition analysis, it is suggested that a more aggressive import
      policy was useful for curbing domestic and global emissions, and the transfer of
      advanced production technologies and emission control technologies from developed
      to developing countries should be a compulsory global environmental policy option
      to mitigate the possible leakage of pollution emissions caused by international
      trade.

PMID- 28441398
TI  - The effects of immune protein CD3zeta development and degeneration of retinal
      neurons after optic nerve injury.
AB  - Major histocompatibility complex (MHC) class I molecules and their receptors play
      fundamental roles in neuronal death during diseases. T-cell receptors (TCR)
      function as MHCI receptor on T-cells and both MHCI and a key component of TCR,
      CD3zeta, are expressed by mouse retinal ganglion cells (RGCs) and displaced
      amacrine cells. Mutation of these molecules compromises the development of RGCs.
      We investigated whether CD3zeta regulates the development and degeneration of
      amacrine cells after RGC death. Surprisingly, mutation of CD3zeta not only
      impairs the proper development of amacrine cells expressing CD3zeta but also
      those not expressing CD3zeta. In contrast to effects of MHCI and its receptor,
      PirB, on other neurons, mutation of CD3zeta has no effect on RGC death and
      starburst amacrine cells degeneration after optic nerve crush. Thus, unlike MHCI
      and PirB, CD3zeta regulates the development of RGCs and amacrine cells but not
      their degeneration after optic nerve crush.

PMID- 28441400
TI  - A genomics approach identifies selective effects of trans-resveratrol in cerebral
      cortex neuron and glia gene expression.
AB  - The mode of action of trans-resveratrol, a promising lead compound for the
      development of neuroprotective drugs, is unknown. Data from a functional genomics
      study were retrieved with the aim to find differentially expressed genes that may
      be involved in the benefits provided by trans-resveratrol. Genes that showed a
      significantly different expression (p<0.05, cut-off of a two-fold change) in mice
      fed with a control diet or a control diet containing trans-resveratrol were
      different in cortex, heart and skeletal muscle. In neocortex, we identified 4 up
      regulated (Strap, Pkp4, Rab2a, Cpne3) and 22 down-regulated (Actn1, Arf3,
      Atp6v01, Atp1a3, Atp1b2, Cacng7, Crtc1, Dbn1, Dnm1, Epn1, Gfap, Hap, Mark41,
      Rab5b, Nrxn2, Ogt, Palm, Ptprn2, Ptprs, Syn2, Timp2, Vamp2) genes upon trans
      resveratrol consumption. Network analysis of gene products provided evidence of
      plakophilin 4 up-regulation as a triggering factor for down-regulation of events
      related to synaptic vesicle transport and neurotransmitter release via
      underexpression of dynamin1 and Vamp2 (synaptobrevin 2) as node-gene drivers.
      Analysis by RT-qPCR of some of the selected genes in a glioma cell line showed
      that dynamin 1 mRNA was down-regulated even in acute trans-resveratrol
      treatments. Taken all together, these results give insight on the glial-neuronal
      networks involved in the neuroprotective role of trans-resveratrol.

PMID- 28441401
TI  - Ancient genes establish stress-induced mutation as a hallmark of cancer.
AB  - Cancer is sometimes depicted as a reversion to single cell behavior in cells
      adapted to live in a multicellular assembly. If this is the case, one would
      expect that mutation in cancer disrupts functional mechanisms that suppress cell
      level traits detrimental to multicellularity. Such mechanisms should have evolved
      with or after the emergence of multicellularity. This leads to two related, but
      distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are
      younger than the emergence of multicellularity (1000 million years [MY]); and 2)
      genes that are frequently mutated in cancer and whose mutations are functionally
      important for the emergence of the cancer phenotype evolved within the past 1000
      million years, and thus would exhibit an age distribution that is skewed to
      younger genes. In order to investigate these hypotheses we estimated the
      evolutionary ages of all human genes and then studied the probability of mutation
      and their biological function in relation to their age and genomic location for
      both normal germline and cancer contexts. We observed that under a model of
      uniform random mutation across the genome, controlled for gene size, genes less
      than 500 MY were more frequently mutated in both cases. Paradoxically, causal
      genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group.
      When we used functional enrichment analysis to explain this unexpected result we
      discovered that COSMIC genes with recessive disease phenotypes were enriched for
      DNA repair and cell cycle control. The non-mutated genes in these pathways are
      orthologous to those underlying stress-induced mutation in bacteria, which
      results in the clustering of single nucleotide variations. COSMIC genes were less
      common in regions where the probability of observing mutational clusters is high,
      although they are approximately 2-fold more likely to harbor mutational clusters
      compared to other human genes. Our results suggest this ancient mutational
      response to stress that evolved among prokaryotes was co-opted to maintain
      diversity in the germline and immune system, while the original phenotype is
      restored in cancer. Reversion to a stress-induced mutational response is a
      hallmark of cancer that allows for effectively searching "protected" genome space
      where genes causally implicated in cancer are located and underlies the high
      adaptive potential and concomitant therapeutic resistance that is characteristic
      of cancer.

PMID- 28441402
TI  - Sex discordance in asthma and wheeze prevalence in two longitudinal cohorts.
AB  - Sex discordance in asthma prevalence has been previously reported, with higher
      prevalence in males before puberty, and in females after puberty; the adolescent
      "switch". However, cross-sectional studies have suggested a narrowing of this
      discordance in recent decades. We used a combination of cross-sectional and
      longitudinal modelling to examine sex differences in asthma, wheeze and
      longitudinal wheezing phenotypes in two UK birth cohorts, the Avon Longitudinal
      Study of Parents and Children (ALSPAC; born 1991-92 with data from age 0-18
      years) and the Millennium Cohort Study (MCS; born 2000-02 with data from age 3-10
      years). We derived measures of asthma and wheeze from questionnaires completed by
      mothers and cohort children. Previously-derived ALSPAC wheezing phenotype models
      were applied to MCS. Males had a higher prevalence of asthma at 10.7 years in
      ALSPAC (OR 1.45 95%CI: 1.26, 1.66 n = 7778 for current asthma) and MCS (OR 1.42
      95%CI: 1.29, 1.56 n = 6726 for asthma ever) compared to females, decreasing in
      ALSPAC after puberty (OR 0.94 95%CI: 0.79, 1.11 n = 5023 for current asthma at
      16.5 years). In longitudinal models using restricted cubic splines, males had a
      clear excess for asthma in the last 12 months and wheeze in the last 12 months up
      until 16.5 years of age in ALSPAC. Males had an increased risk of all derived
      longitudinal wheezing phenotypes in MCS when compared to never wheeze and no
      evidence of being at lower risk of late wheeze when compared to early wheeze. By
      comparing data in two large, contemporary cohorts we have shown the persistence
      of sex discordance in childhood asthma, with no evidence that the sex discordance
      is narrowing in recent cohorts.

PMID- 28441403
TI  - Chronic pain and sex-differences; women accept and move, while men feel blue.
AB  - PURPOSE: The aim of this study is to explore differences between male and female
      patients entering a rehabilitation program at a pain clinic in order to gain a
      greater understanding of different approaches to be used in rehabilitation.
      METHOD: 1371 patients referred to a specialty pain rehabilitation clinic,
      completed sociodemographic and pain related questionnaires. They rated their pain
      acceptance (CPAQ-8), their kinesiophobia (TSK), the impact of pain in their life
      (MPI), anxiety and depression levels (HAD) and quality of life scales: the SF-36,
      LiSat-11, and the EQ-5D. Because of the large sample size of the study, the
      significance level was set at the p <=.01. RESULTS: Analysis by t-test showed
      that when both sexes experience the same pain severity, women report
      significantly higher activity level, pain acceptance and social support while men
      report higher kinesiophobia, mood disturbances and lower activity level.
      CONCLUSION: Pain acceptance (CPAQ-8) and kinesiophobia (TSK) showed the clearest
      differences between men and women. Pain acceptance and kinesiophobia are
      behaviorally defined and have the potential to be changed.

PMID- 28441404
TI  - Angiopoietin-like-4 and minimal change disease.
AB  - BACKGROUND: Minimal Change Disease (MCD) is the most common type of nephrotic
      syndrome in children. Angiopoietin-like-4 (Angplt4) has been proposed as mediator
      of proteinuria in MCD. The aim of this study was to evaluate the role of Angptl4
      as a biomarker in MCD. METHODS: Patients with biopsy-proven primary MCD, focal
      segmental glomerulosclerosis, membranous nephropathy (60, 52 and 52 respectively)
      and 18 control subjects had urinary and serum Angptl4 measured by Elisa. Frozen
      kidney tissue sections were stained for Angptl4. RESULTS: Angptl4 was not
      identified in glomeruli of MCD patients in relapse. Urinary Angptl4 levels were
      elevated in MCD in relapse as well as in patients with massive proteinuria due to
      other glomerular diseases. CONCLUSION: Neither serum nor urine Angptl4 appear to
      be good biomarkers in MCD. Elevated urinary Angptl4 n glomerular disease appears
      to reflect the degree of proteinuria rather than any specific disease.

PMID- 28441405
TI  - MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in
      Arabidopsis thaliana.
AB  - The conserved protein complex known as Mediator conveys transcriptional signals
      by acting as an intermediary between transcription factors and RNA polymerase II.
      As a result, Mediator subunits play multiple roles in regulating developmental as
      well as abiotic and biotic stress pathways. In this report we identify the head
      domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for
      Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20
      display down-regulation of genes associated with jasmonate signaling and
      biosynthesis while up-regulation of salicylic acid associated pathogenesis
      related genes and reactive oxygen producing and scavenging genes. We propose that
      MED18 and MED20 form a sub-domain within Mediator that controls the balance of
      salicylic acid and jasmonate associated defense pathways.

PMID- 28441406
TI  - Head and pelvic movement asymmetries at trot in riding horses in training and
      perceived as free from lameness by the owner.
AB  - Recent studies evaluating horses in training and considered free from lameness by
      their owners have identified a large proportion of horses with motion
      asymmetries. However the prevalence, type and magnitude of asymmetries when
      trotting in a straight line or on the lunge have not been investigated. The aim
      of this study was to objectively investigate the presence of motion asymmetries
      in riding horses in training by identifying the side and quantifying the degree
      and type (impact, pushoff) of forelimb and hind limb asymmetries found during
      straight line trot and on the lunge. In a cross-sectional study, vertical head
      and pelvic movement symmetry was measured in 222 Warmblood type riding horses,
      all without perceived performance issues and considered free from lameness by
      their owners. Body-mounted uni-axial accelerometers were used and differences
      between maximum and minimum head (HDmax, HDmin) and pelvic (PDmax, PDmin)
      vertical displacement between left and right forelimb and hind limb stances were
      calculated during straight line trot and on the lunge. Previously reported
      symmetry thresholds were used. The thresholds for symmetry were exceeded in 161
      horses for at least one variable while trotting in a straight line, HDmin (n =
      58, mean 14.3 mm, SD 7.1), HDmax (n = 41, mean 12.7 mm, SD 5.5), PDmax (n = 87,
      mean 6.5 mm, SD 3.10), PDmin (n = 79, mean 5.7 mm, SD 2.1). Contralateral and
      ipsilateral concurrent forelimb and hind limb asymmetries were detected in 41 and
      49 horses, respectively. There was a linear association between the straight line
      PDmin values and the values on the lunge with the lame limb to the inside of the
      circle. A large proportion (72.5%) of horses in training which were perceived as
      free from lameness by their owner showed movement asymmetries above previously
      reported asymmetry thresholds during straight line trot. It is not known to what
      extent these asymmetries are related to pain or to mechanical abnormalities.
      Therefore, one of the most important questions that must be addressed is how
      objective asymmetry scores can be translated into pain, orthopedic abnormality,
      or any type of unsoundness.

PMID- 28441407
TI  - Changes in secondary metabolites in the halophytic putative crop species Crithmum
      maritimum L., Triglochin maritima L. and Halimione portulacoides (L.) Aellen as
      reaction to mild salinity.
AB  - It is assumed that salinity enhances the concentration of valuable metabolites in
      halophytes. The objective was to find a salt concentration and a point in time at
      which the yield for the valuable metabolites was maximal. Therefore, three
      different halophyte species were grown under different salinities and harvested
      over a period from shortly after stress induction up to three weeks. Various
      reaction patterns were found in the metabolite composition of the analyzed plant
      material. Halimione portulacoides showed a "short term response", indicated by an
      increase in all metabolites analyzed after a few hours, whereas Crithmum
      maritimum showed a "long term response" through accumulation of proline starting
      after days. Triglochin maritima did not change in metabolite concentration, but
      like the other plant species the biomass was reduced by salinity. Generally, a
      higher production in secondary metabolites by higher salinity was outbalanced by
      a reduction in biomass production. Concentrations of analyzed antioxidants showed
      a similar reaction and correlated with each other.

PMID- 28441408
TI  - Short-term Internet search using makes people rely on search engines when facing
      unknown issues.
AB  - The Internet search engines, which have powerful search/sort functions and ease
      of use features, have become an indispensable tool for many individuals. The
      current study is to test whether the short-term Internet search training can make
      people more dependent on it. Thirty-one subjects out of forty subjects completed
      the search training study which included a pre-test, a six-day's training of
      Internet search, and a post-test. During the pre- and post- tests, subjects were
      asked to search online the answers to 40 unusual questions, remember the answers
      and recall them in the scanner. Un-learned questions were randomly presented at
      the recalling stage in order to elicited search impulse. Comparing to the pre
      test, subjects in the post-test reported higher impulse to use search engines to
      answer un-learned questions. Consistently, subjects showed higher brain
      activations in dorsolateral prefrontal cortex and anterior cingulate cortex in
      the post-test than in the pre-test. In addition, there were significant positive
      correlations self-reported search impulse and brain responses in the frontal
      areas. The results suggest that a simple six-day's Internet search training can
      make people dependent on the search tools when facing unknown issues. People are
      easily dependent on the Internet search engines.

PMID- 28441409
TI  - A hypomorphic PIGA gene mutation causes severe defects in neuron development and
      susceptibility to complement-mediated toxicity in a human iPSC model.
AB  - Mutations in genes involved in glycosylphosphatidylinositol (GPI) anchor
      biosynthesis underlie a group of congenital syndromes characterized by severe
      neurodevelopmental defects. GPI anchored proteins have diverse roles in cell
      adhesion, signaling, metabolism and complement regulation. Over 30 enzymes are
      required for GPI anchor biosynthesis and PIGA is involved in the first step of
      this process. A hypomorphic mutation in the X-linked PIGA gene (c.1234C>T) causes
      multiple congenital anomalies hypotonia seizure syndrome 2 (MCAHS2), indicating
      that even partial reduction of GPI anchored proteins dramatically impairs central
      nervous system development, but the mechanism is unclear. Here, we established a
      human induced pluripotent stem cell (hiPSC) model containing the PIGAc.1234C>T
      mutation to study the effects of a hypomorphic allele of PIGA on neuronal
      development. Neuronal differentiation from neural progenitor cells generated by
      EB formation in PIGAc.1234C>T is significantly impaired with decreased
      proliferation, aberrant synapse formation and abnormal membrane depolarization.
      The results provide direct evidence for a critical role of GPI anchor proteins in
      early neurodevelopment. Furthermore, neural progenitors derived from
      PIGAc.1234C>T hiPSCs demonstrate increased susceptibility to complement-mediated
      cytotoxicity, suggesting that defective complement regulation may contribute to
      neurodevelopmental disorders.

PMID- 28441410
TI  - Creating and parameterizing patient-specific deep brain stimulation pathway
      activation models using the hyperdirect pathway as an example.
AB  - BACKGROUND: Deep brain stimulation (DBS) is an established clinical therapy and
      computational models have played an important role in advancing the technology.
      Patient-specific DBS models are now common tools in both academic and industrial
      research, as well as clinical software systems. However, the exact methodology
      for creating patient-specific DBS models can vary substantially and important
      technical details are often missing from published reports. OBJECTIVE: Provide a
      detailed description of the assembly workflow and parameterization of a patient
      specific DBS pathway-activation model (PAM) and predict the response of the
      hyperdirect pathway to clinical stimulation. METHODS: Integration of multiple
      software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation
      and visualization of a DBS PAM. An example DBS PAM was developed using 7T
      magnetic resonance imaging data from a single unilaterally implanted patient with
      Parkinson's disease (PD). This detailed description implements our best
      computational practices and most elaborate parameterization steps, as defined
      from over a decade of technical evolution. RESULTS: Pathway recruitment curves
      and strength-duration relationships highlight the non-linear response of axons to
      changes in the DBS parameter settings. CONCLUSION: Parameterization of patient
      specific DBS models can be highly detailed and constrained, thereby providing
      confidence in the simulation predictions, but at the expense of time demanding
      technical implementation steps. DBS PAMs represent new tools for investigating
      possible correlations between brain pathway activation patterns and clinical
      symptom modulation.

PMID- 28441411
TI  - Comparative transcriptome and proteome analysis reveals a global impact of the
      nitrogen regulators AreA and AreB on secondary metabolism in Fusarium fujikuroi.
AB  - The biosynthesis of multiple secondary metabolites in the phytopathogenic
      ascomycete Fusarium fujikuroi is strongly affected by nitrogen availability.
      Here, we present the first genome-wide transcriptome and proteome analysis that
      compared the wild type and deletion mutants of the two major nitrogen regulators
      AreA and AreB. We show that AreB acts not simply as an antagonist of AreA
      counteracting the expression of AreA target genes as suggested based on the yeast
      model. Both GATA transcription factors affect a large and diverse set of common
      as well as specific target genes and proteins, acting as activators and
      repressors. We demonstrate that AreA and AreB are not only involved in fungal
      nitrogen metabolism, but also in the control of several complex cellular
      processes like carbon metabolism, transport and secondary metabolism. We show
      that both GATA transcription factors can be considered as master regulators of
      secondary metabolism as they affect the expression of more than half of the 47
      putative secondary metabolite clusters identified in the genome of F. fujikuroi.
      While AreA acts as a positive regulator of many clusters under nitrogen-limiting
      conditions, AreB is able to activate and repress gene clusters (e.g. bikaverin)
      under nitrogen limitation and sufficiency. In addition, ChIP analyses revealed
      that loss of AreA or AreB causes histone modifications at some of the regulated
      gene clusters.

PMID- 28441412
TI  - The role of climate and environmental variables in structuring bird assemblages
      in the Seasonally Dry Tropical Forests (SDTFs).
AB  - Understanding the processes that influence species diversity is still a challenge
      in ecological studies. However, there are two main theories to discuss this
      topic, the niche theory and the neutral theory. Our objective was to understand
      the importance of environmental and spatial processes in structuring bird
      communities within the hydrological seasons in dry forest areas in northeastern
      Brazil. The study was conducted in two National Parks, the Serra da Capivara and
      Serra das Confusoes National Parks, where 36 areas were sampled in different
      seasons (dry, dry/rainy transition, rainy, rainy/dry transition), in 2012 and
      2013. We found with our results that bird species richness is higher in the rainy
      season and lower during the dry season, indicating a strong influence of
      seasonality, a pattern also found for environmental heterogeneity. Richness was
      explained by local environmental factors, while species composition was explained
      by environmental and spatial factors. The environmental factors were more
      important in explaining variations in composition. Climate change predictions
      have currently pointed out frequent drought events and a rise in global
      temperature by 2050, which would lead to changes in species behavior and to
      increasing desertification in some regions, including the Caatinga. In addition,
      the high deforestation rates and the low level of representativeness of the
      Caatinga in the conservation units negatively affects bird communities. This
      scenario has demonstrated how climatic factors affect individuals, and,
      therefore, should be the starting point for conservation initiatives to be
      developed in xeric environments.

PMID- 28441413
TI  - Langerhans cells prevent subbasal nerve damage and upregulate neurotrophic
      factors in dry eye disease.
AB  - The functional role of Langerhans cells (LCs) in ocular surface inflammation and
      nerve damage in dry eye (DE) disease has yet to be determined. This study was
      performed to investigate this relationship through both clinical study on DE
      patients and in vivo mouse models with induced DE disease. In a cross-sectional
      case-control study (54 eyes of DE patients; 34 eyes of control patients), average
      cell density, area, and process length of LCs were measured using confocal
      microscopy. Data were analyzed to determine whether changes in LCs are correlated
      with subbasal nerve plexus (SNP) parameters (nerve density, beading, and
      tortuosity). In DE patients, SNP density marginally decreased and nerve beading
      and tortuosity were significantly increased compared to the control group. The
      total number of LCs significantly increased in DE patients, and some LCs with
      elongated processes were found to be attached to nerve fibers. Interestingly,
      nerve loss and deformation were correlated with inactivation of LCs. In an in
      vivo experiment to elucidate the role of LCs in ocular surface inflammation and
      corneal nerve loss, we used a genetically modified mouse model (CD207-DTR) that
      reduced the population of CD207 (Langerin) expressing cells by injection of
      diphtheria toxin. In CD207-depleted mice with DE disease (CD207-dDTR+DE), corneal
      nerves in the central region were significantly decreased, an effect that was not
      observed in wild-type (WT)+DE mice. In CD207-dDTR+DE mice, infiltration of CD4+,
      CD19+, CD45+, and CD11b+ cells into the ocular surface was increased, as
      confirmed by flow cytometry. Increased IL-17 and IFN-gamma mRNA levels, and
      decreased expression of neurotrophic factors and neurotransmitters, were also
      found in the CD207-dDTR+DE mice. These data support a functional role for LCs in
      negatively regulating ocular surface inflammation and exhibiting a
      neuroprotective function in DE disease.

PMID- 28441414
TI  - Regional early and progressive loss of brain pericytes but not vascular smooth
      muscle cells in adult mice with disrupted platelet-derived growth factor receptor
      beta signaling.
AB  - Pericytes regulate key neurovascular functions of the brain. Studies in pericyte
      deficient transgenic mice with aberrant signaling between endothelial-derived
      platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor
      receptor beta (PDGFRbeta) in pericytes have contributed to better understanding
      of the role of pericytes in the brain. Here, we studied PdgfrbetaF7/F7 mice,
      which carry seven point mutations that disrupt PDGFRbeta signaling causing loss
      of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain. We
      asked whether these mice have a stable or progressive vascular phenotype after
      birth, and whether both pericyte and VSMCs populations are affected in the adult
      brain. We found an early and progressive region-dependent loss of brain
      pericytes, microvascular reductions and blood-brain barrier (BBB) breakdown,
      which were more pronounced in the cortex, hippocampus and striatum than in the
      thalamus, whereas VSMCs population remained unaffected at the time when pericyte
      loss was already established. For example, compared to age-matched controls,
      PdgfrbetaF7/F7 mice between 4-6 and 36-48 weeks of age developed a region
      dependent loss in pericyte coverage (22-46, 24-44 and 4-31%) and cell numbers (36
      49, 34-64 and 11-36%), reduction in capillary length (20-39, 13-46 and 1-30%),
      and an increase in extravascular fibrinogen-derived deposits (3.4-5.2, 2.8-4.1
      and 0-3.6-fold) demonstrating BBB breakdown in the cortex, hippocampus and
      thalamus, respectively. Capillary reductions and BBB breakdown correlated with
      loss of pericyte coverage. Our data suggest that PdgfrbetaF7/F7 mice develop an
      aggressive and rapid vascular phenotype without appreciable early involvement of
      VSMCs, therefore providing a valuable model to study regional effects of pericyte
      loss on brain vascular and neuronal functions. This model could be a useful tool
      for future studies directed at understanding the role of pericytes in the
      pathogenesis of neurological disorders associated with pericyte loss such as
      vascular dementia, Alzheimer's disease, amyotrophic lateral sclerosis, stroke and
      human immunodeficiency virus-associated neurocognitive disorder.

PMID- 28441415
TI  - Pax7 remodels the chromatin landscape in skeletal muscle stem cells.
AB  - Pluripotent stem cells (PSC) hold great promise for the treatment of human
      skeletal muscle diseases. However, it remains challenging to convert PSC to
      skeletal muscle cells, and the mechanisms by which the master regulatory
      transcription factor, Pax7, promotes muscle stem (satellite) cell identity are
      not yet understood. We have taken advantage of PSC-derived skeletal muscle
      precursor cells (iPax7), wherein the induced expression of Pax7 robustly
      initiates the muscle program and enables the in vitro generation of precursors
      that seed the satellite cell compartment upon transplantation. Remarkably, we
      found that chromatin accessibility in myogenic precursors pre-figures subsequent
      activation of myogenic differentiation genes. We also found that Pax7 binding is
      generally restricted to euchromatic regions and excluded from H3K27 tri
      methylated regions in muscle cells, suggesting that recruitment of this factor is
      circumscribed by chromatin state. Further, we show that Pax7 binding induces
      dramatic, localized remodeling of chromatin characterized by the acquisition of
      histone marks associated with enhancer activity and induction of chromatin
      accessibility in both muscle precursors and lineage-committed myoblasts.
      Conversely, removal of Pax7 leads to rapid reversal of these features on a subset
      of enhancers. Interestingly, another cluster of Pax7 binding sites is associated
      with a durably accessible and remodeled chromatin state after removal of Pax7,
      and persistent enhancer accessibility is associated with subsequent, proximal
      binding by the muscle regulatory factors, MyoD1 and myogenin. Our studies provide
      new insights into the epigenetic landscape of skeletal muscle stem cells and
      precursors and the role of Pax7 in satellite cell specification.

PMID- 28441416
TI  - Ethanol itself is a holoprosencephaly-inducing teratogen.
AB  - Ethanol is a teratogen, inducing a variety of structural defects in developing
      humans and animals that are exposed in utero. Mechanisms of ethanol
      teratogenicity in specific defects are not well understood. Oxidative metabolism
      of ethanol by alcohol dehydrogenase or cytochrome P450 2E1 has been implicated in
      some of ethanol's teratogenic effects, either via production of acetaldehyde or
      competitive inhibition of retinoic acid synthesis. Generalized oxidative stress
      in response to ethanol may also play a role in its teratogenicity. Among the
      developmental defects that ethanol has been implicated in is holoprosencephaly, a
      failure to define the midline of the forebrain and midface that is associated
      with a deficiency in Sonic hedgehog pathway function. Etiologically,
      holoprosencephaly is thought to arise from a complex combination of genetic and
      environmental factors. We have developed a gene-environment interaction model of
      holoprosencephaly in mice, in which mutation of the Sonic hedgehog coreceptor,
      Cdon, synergizes with transient in utero exposure to ethanol. This system was
      used to address whether oxidative metabolism is required for ethanol's
      teratogenic activity in holoprosencephaly. We report here that t-butyl alcohol,
      which is neither a substrate nor an inhibitor of alcohol dehydrogenases or
      Cyp2E1, is a potent inducer of holoprosencephaly in Cdon mutant mice.
      Additionally, antioxidant treatment did not prevent ethanol- or t-butyl alcohol
      induced HPE in these mice. These findings are consistent with the conclusion that
      ethanol itself, rather than a consequence of its metabolism, is a
      holoprosencephaly-inducing teratogen.

PMID- 28441417
TI  - Minimum lethal concentration of sodium hypochlorite for the amphibian pathogen
      Batrachochytrium dendrobatidis.
AB  - Sodium hypochlorite (NaOCl) is the active ingredient in household bleach and is
      commonly used as a disinfectant to clean equipment contaminated by the amphibian
      pathogen Batrachochytrium dendrobatidis (Bd) in lab husbandry and field studies.
      We conducted a series of replicated exposure trials using a single Global
      Pandemic Lineage Bd isolate from Panama (JEL 310) and concentrations of NaOCl
      ranging from 0.006% to 0.6% for exposure times ranging from 30 seconds to 15
      minutes to determine the minimum lethal concentration of NaOCl for this isolate
      of Bd. Sodium hypochlorite completely killed Bd at a concentration of 0.03%
      during a 15-minute exposure time, while 0.12% NaOCl was effective at all exposure
      times (30s-15min).

PMID- 28441419
TI  - Correction: Fluoride Regulate Osteoblastic Transforming Growth Factor-beta1
      Signaling by Mediating Recycling of the Type I Receptor ALK5.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0170674.].

PMID- 28441418
TI  - Relationship between acromial morphological variation and subacromial
      impingement: A three-dimensional analysis.
AB  - PURPOSE: To evaluate the association of acromial morphology and subacromial
      impingement. METHODS: Bilateral shoulder computed tomography was performed in 138
      patients who received shoulder arthroscopy. Measured parameters included:
      acromial tilt (AT), modified acromial tilt (mAT), acromial slope (AS),
      acromiohumeral interval (AHI), lateral acromial angle (LAA), acromial index (AI),
      critical shoulder angle (CSA), acromial anterior protrusion (AAP), and acromial
      inferior protrusion (AIP). Acromial morphological characteristics were compared
      between groups. Side-to-side differences were assessed between affected and non
      affected shoulders. Intra- and inter-observer agreements for each parameter were
      calculated. RESULTS: AT (25.90 vs. 29.41 degrees ), mAT (18.88 vs. 22.64 degrees
      ), and AHI (5.46 vs. 6.47 mm) were significantly smaller in impinged patients.
      The impingement group demonstrated significantly larger AI (63.50 vs. 59.84%),
      CSA (31.78 vs. 28.74 degrees ), AAP (7.13 vs. 5.32 mm), and AIP (5.51 vs. 4.04
      mm). Regarding side-to-side comparison, the acromial morphology was significantly
      different between the affected and non-affected shoulders in impinged patients,
      while the difference was slight and insignificant in control patients. All,
      except AS and LAA, measured parameters demonstrated good intra- and inter
      observer agreements. CONCLUSIONS: Three-dimensional reconstructed CT scan is a
      reliable method to measure shoulder morphology. The acromial morphological
      variation is related with sub acromial impingement, however, the causal
      relationship of them should be further explored.

PMID- 28441420
TI  - Mapping of the brain hemodynamic responses to sensorimotor stimulation in a
      rodent model: A BOLD fMRI study.
AB  - Blood Oxygenation Level Dependent functional MRI (BOLD fMRI) during electrical
      paw stimulation has been widely used in studies aimed at the understanding of the
      somatosensory network in rats. However, despite the well-established anatomical
      connections between cortical and subcortical structures of the sensorimotor
      system, most of these functional studies have been concentrated on the cortical
      effects of sensory electrical stimulation. BOLD fMRI study of the integration of
      a sensorimotor input across the sensorimotor network requires an appropriate
      methodology to elicit functional activation in cortical and subcortical areas
      owing to the regional differences in both neuronal and vascular architectures
      between these brain regions. Here, using a combination of low level anesthesia,
      long pulse duration of the electrical stimulation along with improved spatial and
      temporal signal to noise ratios, we provide a functional description of the main
      cortical and subcortical structures of the sensorimotor rat brain. With this
      calibrated fMRI protocol, unilateral non-noxious sensorimotor electrical hindpaw
      stimulation resulted in robust positive activations in the contralateral
      sensorimotor cortex and bilaterally in the sensorimotor thalamus nuclei, whereas
      negative activations were observed bilaterally in the dorsolateral caudate
      putamen. These results demonstrate that, once the experimental setup allowing
      necessary spatial and temporal signal to noise ratios is reached, hemodynamic
      changes related to neuronal activity, as preserved by the combination of a soft
      anesthesia with a soft muscle relaxation, can be measured within the sensorimotor
      network. Moreover, the observed responses suggest that increasing pulse duration
      of the electrical stimulus adds a proprioceptive component to the sensory input
      that activates sensorimotor network in the brain, and that these activation
      patterns are similar to those induced by digits paw's movements. These findings
      may find application in fMRI studies of sensorimotor disorders within cortico
      basal network in rodents.

PMID- 28441421
TI  - High prevalence of MRSA and ESBL among asylum seekers in the Netherlands.
AB  - Migration is one of the risk factors for the spread of multidrug-resistant
      organisms (MDRO). The increasing influx of migrants challenges local health care
      systems. To provide evidence for both hospital hygiene measure and empirical
      antibiotic therapy, we analysed all cultures performed in asylum seekers between
      January 1st 2014 and December 31st 2015 for methicillin resistant Staphylococcus
      aureus (MRSA) and for multidrug-resistant Enterobacteriaceae (MDRE). We compared
      these with cultures from the Dutch patient population with risk factors for
      carriage of MDRO. A total of 7181 patients were screened for MRSA. 7357 S. aureus
      were isolated in clinical cultures. Of 898 screened asylum seekers, almost 10%
      were MRSA positive. Of 118 asylum seekers with S. aureus in clinical cultures
      almost 19% were MRSA positive. The general patient population had a 1.3% rate of
      MRSA in S. aureus isolates. A higher rate of Panton-Valentine leukocidin (PVL)
      positive strains (RR: 2.4; 95% CI: 1.6-3.4) was found in asylum seekers compared
      to the general patient population. In 33475 patients one or more
      Enterobacteriaceae were obtained. More than 21% of the asylum seekers were
      carrier of MDRE, most of them producing extended spectrum beta-lactamases
      (20.3%). 5.1% of the general patient population was MDRE carrier. It can be
      concluded that asylum seekers present with higher rate of MDRO compared to the
      general patient population. These results justify continued screening of asylum
      seekers to anticipate multidrug-resistant organisms during hospital care of
      patients.

PMID- 28441422
TI  - Automated detection of hospital outbreaks: A systematic review of methods.
AB  - OBJECTIVES: Several automated algorithms for epidemiological surveillance in
      hospitals have been proposed. However, the usefulness of these methods to detect
      nosocomial outbreaks remains unclear. The goal of this review was to describe
      outbreak detection algorithms that have been tested within hospitals, consider
      how they were evaluated, and synthesize their results. METHODS: We developed a
      search query using keywords associated with hospital outbreak detection and
      searched the MEDLINE database. To ensure the highest sensitivity, no limitations
      were initially imposed on publication languages and dates, although we
      subsequently excluded studies published before 2000. Every study that described a
      method to detect outbreaks within hospitals was included, without any exclusion
      based on study design. Additional studies were identified through citations in
      retrieved studies. RESULTS: Twenty-nine studies were included. The detection
      algorithms were grouped into 5 categories: simple thresholds (n = 6), statistical
      process control (n = 12), scan statistics (n = 6), traditional statistical models
      (n = 6), and data mining methods (n = 4). The evaluation of the algorithms was
      often solely descriptive (n = 15), but more complex epidemiological criteria were
      also investigated (n = 10). The performance measures varied widely between
      studies: e.g., the sensitivity of an algorithm in a real world setting could vary
      between 17 and 100%. CONCLUSION: Even if outbreak detection algorithms are useful
      complementary tools for traditional surveillance, the heterogeneity in results
      among published studies does not support quantitative synthesis of their
      performance. A standardized framework should be followed when evaluating outbreak
      detection methods to allow comparison of algorithms across studies and synthesis
      of results.

PMID- 28441423
TI  - Reproductive parameters and cub survival of brown bears in the Rusha area of the
      Shiretoko Peninsula, Hokkaido, Japan.
AB  - Knowing the reproductive characteristics of a species is essential for the
      appropriate conservation and management of wildlife. In this study, we
      investigated the demographic parameters, including age of primiparity, litter
      size, inter-birth interval, reproductive rate, and cub survival rate, of Hokkaido
      brown bears (Ursus arctos yesoensis) in the Rusha area on the Shiretoko
      Peninsula, Hokkaido, Japan, based on a long-term, individual-based monitoring
      survey. A total of 15 philopatric females were observed nearly every year from
      2006 to 2016, and these observations were used to estimate reproductive
      parameters. The mean age of primiparity was 5.3 +/- 0.2 (SE) years (n = 7, 95% CI
      = 5.0-5.6). We observed 81 cubs in 46 litters from 15 bears. Litter size ranged
      from one to three cubs, and averaged 1.76 +/- 0.08 (SE) cubs/litter (95% CI =
      1.61-1.91). Inter-birth intervals ranged from 1 to 4 years, and the mean value
      was estimated as 2.43 (95% CI = 2.16-2.76) and 2.53 (95% CI = 2.26-2.85) years in
      all litters and in litters that survived at least their first year, respectively.
      The reproductive rate was estimated from 0.70 to 0.76 young
      born/year/reproductive adult female, depending on the method of calculation. The
      cub survival rate between 0.5 and 1.5 years ranged from 60 to 73%. Most cub
      disappearances occurred in July and August, suggesting that cub mortality is
      mainly due to poor nutrition in the summer. All reproductive parameters observed
      in the Rusha area on the Shiretoko Peninsula fell within the range reported in
      Europe and North America, and were among the lowest or shortest age of
      primiparity, litter size, and inter-birth intervals, and ranked at a high level
      for reproductive rate.

PMID- 28441424
TI  - Correction: Suicide prevention through means restriction: Impact of the 2008-2011
      pesticide restrictions on suicide in Sri Lanka.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0172893.].

PMID- 28441425
TI  - Role of route previewing strategies on climbing fluency and exploratory
      movements.
AB  - This study examined the role of route previewing strategies on climbing fluency
      and on exploratory movements of the limbs, in order to understand whether
      previewing helps people to perceive and to realize affordances. Eight
      inexperienced and ten experienced climbers previewed a 10 m high route of 5b
      difficulty on French scale, then climbed it with a top-rope as fluently as
      possible. Gaze behavior was collected from an eye tracking system during the
      preview and allowed us to determine the number of times they scanned the route,
      and which of four route previewing strategies (fragmentary, ascending,
      zigzagging, and sequence-of-blocks) they used. Five inertial measurement units
      (IMU) (3D accelerometer, 3D gyroscope, 3D magnetometer) were attached to the hip,
      both feet, and forearms to analyze the vertical acceleration and direction of
      each limb and hip during the ascent. We were able to detect movement and
      immobility phases of each IMU using segmentation and classification processes.
      Depending on whether the limbs and/or hip were moving, five states of behavior
      were detected: immobility, postural regulation, hold exploration, hold change,
      and hold traction. Using cluster analysis we identified four clusters of gaze
      behavior during route previewing depending on route preview duration, number of
      scan paths, fixations duration, ascending, zigzagging, and sequence-of-blocks
      strategies. The number of scan paths was positively correlated with relative
      duration of exploration and negatively correlated with relative duration of hold
      changes during the ascent. Additionally, a high relative duration of sequence-of
      blocks strategy and zigzagging strategy were associated with a high relative
      duration of immobility during the ascent. Route previewing might help to pick up
      functional information about reachable, graspable, and usable holds, in order to
      chain movements together and to find the route. In other words, route previewing
      might contribute to perceiving and realizing nested affordances.

PMID- 28441427
TI  - Programmable type III-A CRISPR-Cas DNA targeting modules.
AB  - The CRISPR-Cas systems provide invader defense in a wide variety of prokaryotes,
      as well as technologies for many powerful applications. The Type III-A or Csm
      CRISPR-Cas system is one of the most widely distributed across prokaryotic phyla,
      and cleaves targeted DNA and RNA molecules. In this work, we have constructed
      modules of Csm systems from 3 bacterial species and heterologously expressed the
      functional modules in E. coli. The modules include a Cas6 protein and a CRISPR
      locus for crRNA production, and Csm effector complex proteins. The expressed
      modules from L. lactis, S. epidermidis and S. thermophilus specifically eliminate
      invading plasmids recognized by the crRNAs of the systems. Characteristically,
      activation of plasmid targeting activity depends on transcription of the plasmid
      sequence recognized by the crRNA. Activity was not observed when transcription of
      the crRNA target sequence was blocked, or when the opposite strand or a non
      target sequence was transcribed. Moreover, the Csm module can be programmed to
      recognize plasmids with novel target sequences by addition of appropriate crRNA
      coding sequences to the module. These systems provide a platform for
      investigation of Type III-A CRISPR-Cas systems in E. coli, and for introduction
      of programmable transcription-activated DNA targeting into novel organisms.

PMID- 28441426
TI  - Identification of genes associated with dissociation of cognitive performance and
      neuropathological burden: Multistep analysis of genetic, epigenetic, and
      transcriptional data.
AB  - INTRODUCTION: The molecular underpinnings of the dissociation of cognitive
      performance and neuropathological burden are poorly understood, and there are
      currently no known genetic or epigenetic determinants of the dissociation.
      METHODS AND FINDINGS: "Residual cognition" was quantified by regressing out the
      effects of cerebral pathologies and demographic characteristics on global
      cognitive performance proximate to death. To identify genes influencing residual
      cognition, we leveraged neuropathological, genetic, epigenetic, and
      transcriptional data available for deceased participants of the Religious Orders
      Study (n = 492) and the Rush Memory and Aging Project (n = 487). Given that our
      sample size was underpowered to detect genome-wide significance, we applied a
      multistep approach to identify genes influencing residual cognition, based on our
      prior observation that independent genetic and epigenetic risk factors can
      converge on the same locus. In the first step (n = 979), we performed a genome
      wide association study with a predefined suggestive p < 10-5, and nine
      independent loci met this threshold in eight distinct chromosomal regions. Three
      of the six genes within 100 kb of the lead SNP are expressed in the dorsolateral
      prefrontal cortex (DLPFC): UNC5C, ENC1, and TMEM106B. In the second step, in the
      subset of participants with DLPFC DNA methylation data (n = 648), we found that
      residual cognition was related to differential DNA methylation of UNC5C and ENC1
      (false discovery rate < 0.05). In the third step, in the subset of participants
      with DLPFC RNA sequencing data (n = 469), brain transcription levels of UNC5C and
      ENC1 were evaluated for their association with residual cognition: RNA levels of
      both UNC5C (estimated effect = -0.40, 95% CI -0.69 to -0.10, p = 0.0089) and ENC1
      (estimated effect = 0.0064, 95% CI 0.0033 to 0.0096, p = 5.7 * 10-5) were
      associated with residual cognition. In secondary analyses, we explored the
      mechanism of these associations and found that ENC1 may be related to the
      previously documented effect of depression on cognitive decline, while UNC5C may
      alter the composition of presynaptic terminals. Of note, the TMEM106B allele
      identified in the first step as being associated with better residual cognition
      is in strong linkage disequilibrium with rs1990622A (r2 = 0.66), a previously
      identified protective allele for TDP-43 proteinopathy. Limitations include the
      small sample size for the genetic analysis, which was underpowered to detect
      genome-wide significance, the evaluation being limited to a single cortical
      region for epigenetic and transcriptomic data, and the use of categorical
      measures for certain non-amyloid-plaque, non-neurofibrillary-tangle
      neuropathologies. CONCLUSIONS: Through a multistep analysis of cognitive,
      neuropathological, genomic, epigenomic, and transcriptomic data, we identified
      ENC1 and UNC5C as genes with convergent genetic, epigenetic, and transcriptomic
      evidence supporting a potential role in the dissociation of cognition and
      neuropathology in an aging population, and we expanded our understanding of the
      TMEM106B haplotype that is protective against TDP-43 proteinopathy.

PMID- 28441428
TI  - Increased long-term risk of major adverse cardiovascular events in patients with
      carbon monoxide poisoning: A population-based study in Taiwan.
AB  - BACKGROUND: Carbon monoxide (CO) poisoning may cause toxicity to the
      cardiovascular system. However, the association between CO poisoning and the risk
      of major adverse cardiovascular events (MACE) remains unestablished. We
      investigated the incidence of MACE after CO poisoning in Taiwan and evaluated
      whether CO-poisoned individuals had a higher risk of MACE than did the general
      population. METHODS: Using Taiwan's National Health Insurance Research Database
      (NHIRD) during 2005-2013, a nationwide population-based cohort study was
      conducted among patients who experienced CO poisoning between 2005 and 2013. CO
      poisoning was defined according to the International Classification of Diseases,
      Ninth Revision, Clinical Modification codes. The study cohort comprised patients
      with CO poisoning between 2005 and 2010 (N = 13,939). Each patient was matched
      according to age, sex and index date with four randomly selected controls from
      the comparison cohort (N = 55,756). All patients were followed from the study
      date until MACE development, death, or the end of 2013. The hazard ratios for
      MACE were compared between the two cohorts by using Cox proportional hazards
      regressions analyses. RESULTS: Incident cases of MACE were identified from the
      NHIRD. After adjustment for potential confounders, the study cohort was
      independently associated with a higher MACE risk (adjusted hazard ratio, 2.00;
      95% confidence interval, 1.83-2.18). CONCLUSION: This population-based cohort
      study indicated that patients with CO poisoning have a higher risk of MACE than
      do individuals without CO poisoning.

PMID- 28441429
TI  - Correction: Comparison of Prediction Model for Cardiovascular Autonomic
      Dysfunction Using Artificial Neural Network and Logistic Regression Analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0070571.].

PMID- 28441431
TI  - Correction: Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization
      in Adolescent Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0167483.].

PMID- 28441430
TI  - Short telomere length is associated with renal impairment in Japanese subjects
      with cardiovascular risk.
AB  - INTRODUCTION: Short telomere length has been suggested to be associated with
      atherosclerotic changes in Western populations. We examined the relationships
      between leukocyte telomere length and cardiovascular and renal function in a
      Japanese cohort. PARTICIPANTS AND METHODS: We enrolled 770 subjects who each had
      at least one cardiovascular risk factor. The mean age was 59.5 +/- 12.2 years;
      mean BMI was 25.1 +/- 4.6 kg/m2. We measured leukocyte telomere length (LTL) by
      quantitative PCR (T/S ratio), and measured other biomarkers from blood and urine
      samples. In addition, we assessed surrogate markers of arterial stiffness,
      cardiovascular organ damage and kidney function, including flow-mediated
      vasodilation (FMD), pulse wave velocity (PWV), carotid artery augmentation index
      (CAAI), and urinary albumin creatinine ratio (UACR) and eGFR. RESULTS: Leukocyte
      telomere length (T/S ratio) was inversely associated with age (r = -0.194,
      P<0.001), and was lower in men (1.13 +/- 0.29%) than in women (1.20 +/- 0.31%, P
      = 0.002). T/S ratio was positively associated with BMI in women (r = 0.11, P =
      0.047), but not in men. LTL did not show a significant relationship to
      cardiovascular surrogate markers, including arterial stiffness, FMD, and PWV, but
      did show some relationship to CAAI, which was inversely associated with T/S ratio
      only in men (r = -0.159, P = 0.015). LTL did show a significant positive
      association with renal function measured by eGFR (r = 0.16, P<0.001) both in men
      and women. CONCLUSIONS: In this Japanese sample of persons with increased
      cardiovascular risk, telomere length showed a relationship of longer telomere
      length to better renal function, but did not overall show convincing association
      with cardiovascular measures of arterial stiffness and target organ damage.

PMID- 28441432
TI  - Dysbiosis of intestinal microbiota and decrease in paneth cell antimicrobial
      peptide level during acute necrotizing pancreatitis in rats.
AB  - OBJECTIVES: Intestinal barrier dysfunction plays an important role in acute
      necrotizing pancreatitis (ANP) and intestinal microbiota dysbiosis was involved
      in intestinal barrier failure. Paneth cells protect intestinal barrier and are
      associated with intestinal microbiota. Here, we investigated changes in
      intestinal microbiota and antimicrobial peptides of Paneth cells in ileum during
      ANP. METHODS: Rats with ANP were established by retrograde injection of 3.5%
      sodium taurocholate into biliopancreatic duct and sacrificed at 24h and 48h,
      respectively. Injuries of pancreas and distal ileum were evaluated by
      histopathological score. Intestinal barrier function was assessed by plasma
      diamine oxidase activity (DAO) and D-lactate. Systemic and intestinal
      inflammation was evaluated by TNFalpha, IL-1beta and IL-17A concentration by
      ELISA, respectively. 16S rRNA high throughput sequencing on fecal samples was
      used to investigate the changes in intestinal microbiota in the ANP group at 48h.
      Lysozyme and alpha-defensin5 were measured by real-time PCR, western blot and
      immunofluoresence. RESULTS: ANP rats had more severe histopathological injuries
      in pancreas and distal ileum, injured intestinal barrier and increased expression
      of TNFalpha, IL-1beta and IL-17A in plasma and distal ileum compared with those
      of the sham-operated (SO) group. Principal component analysis (PCA) showed
      structural segregation between the SO and ANP groups. Operational taxonomic unit
      (OTU) number and ACE index revealed decreased microbiota diversity in the ANP
      group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. At
      phyla level, Saccharibacteria and Tenericutes decreased significantly. At genus
      level, Escherichia-Shigella and Phascolarctobacterium increased significantly,
      while Candidatus_Saccharimonas, Prevotellaceae_UCG-001, Lachnospiraceae_UCG-001,
      Ruminiclostridium_5 and Ruminococcaceae_UCG-008 decreased significantly. Lysozyme
      and alpha-defensin5 mRNA expression levels decreased significantly in ANP group
      at 48h. Protein expression of lysozyme decreased in ANP groups at 24h and 48h.
      Meanwhile, the relative abundance of Escherichia-Shigella correlated inversely
      with the decrease in lysozyme. CONCLUSION: The disorder in intestinal microbiota
      and decreases of Paneth cell antimicrobial peptides might participate in the
      pathogenesis of intestinal barrier dysfunction during ANP.

PMID- 28441433
TI  - Correction: Loss of genes related to Nucleotide Excision Repair (NER) and
      implications for reductive genome evolution in symbionts of deep-sea vesicomyid
      clams.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0171274.].

PMID- 28441434
TI  - Testing survey-based methods for rapid monitoring of child mortality, with
      implications for summary birth history data.
AB  - INTRODUCTION: Under-five mortality estimates are increasingly used in low and
      middle income countries to target interventions and measure performance against
      global development goals. Two new methods to rapidly estimate under-5 mortality
      based on Summary Birth Histories (SBH) were described in a previous paper and
      tested with data available. This analysis tests the methods using data
      appropriate to each method from 5 countries that lack vital registration systems.
      SBH data are collected across many countries through censuses and surveys, and
      indirect methods often rely upon their quality to estimate mortality rates.
      METHODS AND FINDINGS: The Birth History Imputation method imputes data from a
      recent Full Birth History (FBH) onto the birth, death and age distribution of the
      SBH to produce estimates based on the resulting distribution of child mortality.
      DHS FBHs and MICS SBHs are used for all five countries. In the implementation, 43
      of 70 estimates are within 20% of validation estimates (61%). Mean Absolute
      Relative Error is 17.7.%. 1 of 7 countries produces acceptable estimates. The
      Cohort Change method considers the differences in births and deaths between
      repeated Summary Birth Histories at 1 or 2-year intervals to estimate the
      mortality rate in that period. SBHs are taken from Brazil's PNAD Surveys 2004
      2011 and validated against IGME estimates. 2 of 10 estimates are within 10% of
      validation estimates. Mean absolute relative error is greater than 100%.
      CONCLUSIONS: Appropriate testing of these new methods demonstrates that they do
      not produce sufficiently good estimates based on the data available. We conclude
      this is due to the poor quality of most SBH data included in the study. This has
      wider implications for the next round of censuses and future household surveys
      across many low- and middle- income countries.

PMID- 28441435
TI  - Implementation science: Relevance in the real world without sacrificing rigor.
AB  - Three members of PLOS Medicine's editorial board who are leading researchers in
      implementation science define the characteristics of high-quality studies and
      invite their submission to the journal.

PMID- 28441436
TI  - Environmental DNA assays for the sister taxa sauger (Sander canadensis) and
      walleye (Sander vitreus).
AB  - Sauger (Sander canadensis) and walleye (S. vitreus) are percid fishes that
      naturally co-occur throughout much of the eastern United States. The native range
      of sauger extends into the upper Missouri River drainage where walleye did not
      historically occur, but have been stocked as a sport fish. Sauger populations
      have been declining due to habitat loss, fragmentation, and competition with non
      native species, such as walleye. To effectively manage sauger populations, it is
      necessary to identify areas where sauger occur, and particularly where they co
      occur with walleye. We developed quantitative PCR assays that can detect sauger
      and walleye DNA in filtered water samples. Each assay efficiently detected low
      quantities of target DNA and failed to detect DNA of non-target species with
      which they commonly co-occur.

PMID- 28441438
TI  - Correction: Cytological Observations of the Large Symbiotic Foraminifer
      Amphisorus kudakajimensis Using Calcein Acetoxymethyl Ester.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0165844.].

PMID- 28441437
TI  - Quantitative modeling of responses to chronic ionizing radiation exposure using
      targeted and non-targeted effects.
AB  - The biological effects of chronic ionizing radiation exposure can be difficult to
      study, but important to understand in order to protect the health of
      occupationally-exposed persons and victims of radiological accidents or malicious
      events. They include targeted effects (TE) caused by ionizations within/close to
      nuclear DNA, and non-targeted effects (NTE) caused by damage to other cell
      structures and/or activation of stress-signaling pathways in distant cells. Data
      on radiation damage in animal populations exposed over multiple generations to
      wide ranges of dose rates after the Chernobyl nuclear-power-plant accident are
      very useful for enhancing our understanding of these processes. We used a
      mechanistically-motivated mathematical model which includes TE and NTE to analyze
      a large published data set on chromosomal aberrations in pond snail (Lymnaea
      stagnalis) embryos collected over 16 years from water bodies contaminated by
      Chernobyl fallout, and from control locations. The fraction of embryo cells with
      aberrations increased dramatically (>10-fold) and non-linearly over a dose rate
      range of 0.03-420 MUGy/h (0.00026-3.7 Gy/year). NTE were very important for
      describing the non-linearity of this radiation response: the TE-only model
      (without NTE) performed dramatically worse than the TE+NTE model. NTE were
      predicted to reach 1/2 of maximal intensity at 2.5 MUGy/h (0.022 Gy/year) and to
      contribute >90% to the radiation response slope at dose rates <11 MUGy/h (0.1
      Gy/year). Internally-incorporated 90Sr was possibly more effective per unit dose
      than other radionuclides. The radiation response shape for chromosomal
      aberrations in snail embryos was consistent with data for a different endpoint:
      the fraction of young amoebocytes in adult snail haemolymph. Therefore, radiation
      may affect different snail life stages by similar mechanisms. The importance of
      NTE in our model-based analysis suggests that the search for modulators of NTE
      related signaling pathways could be a promising strategy for mitigating the
      deleterious effects of chronic irradiation.

PMID- 28441440
TI  - Correction: Relationships between Mucosal Antibodies, Non-Typeable Haemophilus
      influenzae (NTHi) Infection and Airway Inflammation in COPD.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0167250.].

PMID- 28441439
TI  - Hemodynamics and gas exchange during chest compressions in neonatal
      resuscitation.
AB  - PURPOSE: Current knowledge about pulmonary/systemic hemodynamics and gas exchange
      during neonatal resuscitation in a model of transitioning fetal circulation with
      fetal shunts and fluid-filled alveoli is limited. Using a fetal lamb asphyxia
      model, we sought to determine whether hemodynamic or gas-exchange parameters
      predicted successful return of spontaneous circulation (ROSC). METHODS: The
      umbilical cord was occluded in 22 lambs to induce asphyxial cardiac arrest.
      Following five minutes of asystole, resuscitation as per AHA-Neonatal
      Resuscitation Program guidelines was initiated. Hemodynamic parameters and serial
      arterial blood gases were assessed during resuscitation. RESULTS: ROSC occurred
      in 18 lambs (82%) at a median (IQR) time of 120 (105-180) seconds. There were no
      differences in hemodynamic parameters at baseline and at any given time point
      during resuscitation between the lambs that achieved ROSC and those that did not.
      Blood gases at arrest prior to resuscitation were comparable between groups.
      However, lambs that achieved ROSC had lower PaO2, higher PaCO2, and lower lactate
      during resuscitation. Increase in diastolic blood pressures induced by
      epinephrine in lambs that achieved ROSC (11 +/-4 mmHg) did not differ from those
      that were not resuscitated (10 +/-6 mmHg). Low diastolic blood pressures were
      adequate to achieve ROSC. CONCLUSIONS: Hemodynamic parameters in a neonatal lamb
      asphyxia model with transitioning circulation did not predict success of ROSC.
      Lactic acidosis, higher PaO2 and lower PaCO2 observed in the lambs that did not
      achieve ROSC may represent a state of inadequate tissue perfusion and/or
      mitochondrial dysfunction.

PMID- 28441441
TI  - A novel, multiplexed, probe-based quantitative PCR assay for the soybean root-
      and stem-rot pathogen, Phytophthora sojae, utilizes its transposable element.
AB  - Phytophthora root rot of soybean [Glycine max (L.) Merr.] is caused by the
      oomycete Phytophthora sojae (Kaufm. & Gerd.). P. sojae has a narrow host range,
      consisting primarily of soybean, and it is a serious pathogen worldwide. It
      exists in root and stem tissues as mycelium, wherein it can form oospores which
      subsequently germinate to release motile, infectious zoospores. Molecular assays
      detecting DNA of P. sojae are useful in disease diagnostics, and for determining
      the presence of the organism in host tissues, soils, and runoff or ponded water
      from potentially infested fields. Such assays as published have utilized ITS
      sequences from the nuclear ribosomal RNA genes in conventional PCR or dye-binding
      quantitative PCR (Q-PCR) but are not amenable to multiplexing, and some of these
      assays did not utilize control strategies for type I or type II errors. In this
      study, we describe primers and a bifunctional probe with specificity to a gypsy
      like retroelement in the P. sojae genome to create a fluorogenic 5'-exonuclease
      linear hydrolysis assay, with a multiplexed internal control reaction detecting
      an exogenous target to validate negative calls, and with uracil-deglycosylase
      mediated protection against carryover contamination. The assay specifically
      detected 13 different P. sojae isolates, and excluded 17 other Phytophthora
      species along with 20 non-Phytophthora fungal and oomycete species pathogenic on
      soybean. A diagnostic limit of detection of 34 fg total P. sojae DNA was observed
      in serial dilutions, equivalent to 0.3 genome, and a practical detection
      sensitivity of four zoospores per sample was achieved, despite losses during DNA
      extraction.

PMID- 28441442
TI  - The effects of a resistance vs. an aerobic single session on attention and
      executive functioning in adults.
AB  - Evidence from recent studies showed that acute aerobic exercise results in
      improvements in different cognitive functions. The goal of this study was to
      assess the influence of acute bouts of aerobic versus resistance exercise on
      attention and executive function in adults. Thirty-nine physically active adults
      (age = 52+/-8 yr) served as participants. Each participant visited the laboratory
      four times: on the first visit participants performed a cognitive test
      (NeuroTrax) followed by an aerobic fitness assessment, as well as maximal
      strength test composed of six exercises. During visits 2-4, participants
      completed the cognitive test before and after the experimental condition, which
      consisted of either 25 min of aerobic exercise or resistance exercise, or
      watching a recorded interview show in a seated position (control condition).
      Findings indicated significantly higher changes in scores of attention after
      acute aerobic exercise (mean change 3.46, 95% CI -0.32, 7.27) than following the
      control condition (mean change -0.64, 95% CI -2.23, 0.96). The changes following
      resistance exercise (mean change -0.67, 95% CI -4.47, 3.13) were not
      significantly different from the changes following the control condition.
      Executive function scores showed a marginally significant improvement following
      acute aerobic (mean change 4.06, 95% CI 1.68, 6.44) and resistance exercise (mean
      change 3.69, 95% CI 0.78, 6.60), but not after control (mean change 0.91, 95% CI 
      1.21, 3.02). We suggest that adults should consider augmenting both modalities
      into their training routines, which may improve their cognition in addition to
      providing other physical benefits.

PMID- 28441443
TI  - The effect of parental factors in children with large cup-to-disc ratios.
AB  - BACKGROUND: To investigate large cup-to-disc ratios (CDR) in children and to
      determine the relationship between parental CDR and clinical characteristics
      associated with glaucoma. METHODS: Two hundred thirty six children aged 6 to 12
      years with CDR >= 0.6 were enrolled in this study. Subjects were classified into
      two groups based on parental CDR: disc suspect children with disc suspect (CDR
      >=0.6) parents and disc suspect children without disc suspect parents. Ocular
      variables were compared between the two groups. RESULTS: Of the 236 disc suspect
      children, 100 (42.4%) had at least one disc suspect parent. Intraocular pressure
      (IOP) was higher in disc suspect children with disc suspect parents (16.52+/-2.66
      mmHg) than in disc suspect children without disc suspect parents (14.38+/-2.30
      mmHg, p = 0.023). In the group with disc suspect parents, vertical CDR
      significantly correlated with IOP (R = -0.325, p = 0.001), average retinal nerve
      fiber layer (RNFL) thickness (R = -0.319, p = 0.001), rim area (R = -0.740, p =
      0.001), and cup volume (R = 0.499, p = 0.001). However, spherical equivalent (R =
      0.333, p = 0.001), AL (R = -0.223, p = 0.009), and disc area (R = 0.325, p =
      0.001) significantly correlated with vertical CDR in disc suspect children
      without disc suspect parents, in contrast to those with disc suspect parents.
      Larger vertical CDR was associated with the presence of disc suspect parents (p =
      0.001), larger disc area (p = 0.001), thinner rim area (p = 0.001), larger
      average CDR (p = 0.001), and larger cup volume (p = 0.021). CONCLUSIONS AND
      RELEVANCE: Family history of large CDR was a significant factor associated with
      large vertical CDR in children. In children with disc suspect parents, there were
      significant correlations between IOP and average RNFL thickness and vertical CDR.

PMID- 28441444
TI  - Contexts of occurrence of child malnutrition in the district of Villaguay, Entre
      Rios, Argentina. A multivariate analysis.
AB  - The analysis of nutritional status is anthropologically important to address the
      complex interaction of biological, social, political, economic and cultural
      factors. To deepen the knowledge about contexts of occurrence of child
      malnutrition, we analyzed nutritional status in relation to socio-environmental
      conditions of residence in children between three and six years from Villaguay,
      Entre Rios, Argentina. We performed a cross-sectional study of 1,435 school
      children of both sexes. Body weight and height were measured and prevalence of
      low height/age (LH/A), low weight/age (LW/A), low BMI/age (LBMI/A), overweight
      (Ow) and obesity (Ob) was calculated using World Health Organization reference
      charts. Socio-environmental information was obtained through a semi-structured
      survey and processed by Categorical Principal Component Analysis (CatPCA).
      Anthropometric data showed 1.5% LW/A, 5.2% LH/A; 0.6% LBMI/A, 20.9% Ow and 10.9%
      Ob. CatPCA allowed us to define four groups (G1-G4) with better (G2), middle (G1)
      and worst (G4) urban socio-environmental conditions and one with rural
      characteristics (G3). G4 presented the highest LH/A prevalence and G2 the highest
      Ow and Ob prevalence (P<0.05). It is concluded that since the distribution of
      malnutrition was not even it may dependent on the context in which children grow
      up. Thus, the higher the socio-economic level, the higher the incidence of
      overweight and obesity. Conversely, at the other end of the social scale,
      undernutrition and increasing weight excess remained major health problems.

PMID- 28441445
TI  - Impact of aberrant cerebral perfusion on resting-state functional MRI: A
      preliminary investigation of Moyamoya disease.
AB  - The impact of chronic cerebral hypoperfusion on resting-state blood oxygen level
      dependent signal fluctuations remains unknown. We aimed to determine whether
      chronic ischemia induces changes in amplitude of low-frequency fluctuations
      (ALFF) and to investigate the correlation between ALFF and perfusion-weighted
      magnetic resonance imaging (PWI) parameters in patients with moyamoya disease
      (MMD). Thirty patients with pre- and postoperative resting-state functional
      magnetic resonance imaging and PWI were included, and thirty normal controls
      underwent resting-state functional magnetic resonance imaging. A decrease in
      preoperative frontal lobe ALFF was observed in patients with MMD. Postoperative
      frontal lobe ALFF showed moderate improvement but still remained lower than those
      in normal controls. The values of mean transit time and time-to-peak, but not
      cerebral blood volume and cerebral blood flow, correlated significantly with
      frontal lobe ALFF. Moreover, there were significant negative correlations between
      changes in frontal lobe PWI parameters and changes in frontal lobe ALFF on both
      operated side and contralateral side after the unilateral revascularization
      surgery. Our results demonstrate that reduced ALFF are closely related to the
      abnormal PWI parameters and vary with the alteration of cerebral perfusion in
      patients with MMD.

PMID- 28441446
TI  - Fetal outcomes and associated factors of adverse outcomes of pregnancy in
      southern Chinese women with systemic lupus erythematosus.
AB  - This study aims to investigate the fetal outcomes and associated factors of
      adverse pregnancy outcomes (APOs) in pregnant women with systemic lupus
      erythematosus (SLE). Clinical data from 251 SLE patients with 263 pregnancies
      from 2001 to 2015 were analyzed retrospectively. APOs occurred in 70.0% of
      pregnancies, in which pregnancy loss occurred in 28.5%; preterm delivery occurred
      in 21.3%; intrauterine growth retardation occurred in 12.2%; and fetal distress
      occurred in 8.0%. Over time, the rate of APOs decreased from 82.8% during
      2001~2005 to 59.6% during 2011~2015. In multivariate analysis, predictors of APOs
      included positive antiphospholipid antibodies (OR 8.4, 95% CI 1.7~40.8, P =
      0.008), lower complement (OR 3.6, 95% CI 1.3~9.9, P = 0.01), hypoalbuminemia (OR
      3.2, 95% CI 1.2~8.3, P = 0.02), and hypertension (OR 14.6, 95% CI 1.5~141.6, P =
      0.02). The use of antimalarial medications was associated with lower risk for
      APOs (OR 0.3, 95% CI 0.1~0.7, P = 0.01). In total, 109 patients underwent fetal
      umbilical artery Doppler in the third trimester. The The adjusted
      systole/diastole (S/D) ratio, pulsatility index (PI) and resistance index (RI) of
      SLE patients with APOs were higher than that of patients without APOs (2.9+/-0.9
      vs. 2.4+/-0.5, P = 0.001). Lupus pregnancy was still at high risk of APOs in
      terms of pregnancy loss and preterm delivery. Umbilical artery Doppler was a good
      monitor method for APOs in the third trimester.

PMID- 28441447
TI  - Tumor response assessment by MRI following stereotactic body radiation therapy
      for hepatocellular carcinoma.
AB  - BACKGROUND: To evaluate the MRI features of a tumor response, local control, and
      predictive factors of local control after stereotactic body radiation therapy
      (SBRT) for hepatocellular carcinoma (HCC). METHODS: Thirty-five consecutive
      patients with 48 HCCs who were treated by SBRT were included in this
      retrospective study. All patients provided written informed consent to be treated
      by SBRT, and prior to inclusion they authorized use of the treatment data for
      further studies. The assessment was made using MRI, with determination of local
      and hepatic responses according to Response Evaluation Criteria in Solid Tumors
      (RECIST) and modified RECIST (mRECIST) criteria during a two-year follow-up.
      RESULTS: The local response rate according to mRECIST was higher than with
      RECIST. A tumor diameter less than 20 mm at baseline was an independent
      predictive factor for RECIST and mRECIST responses, as was diffusion-weighted
      signal for RECIST. During follow-up, a tumor diameter of <20 mm (p = 0.034) and
      absence of a high intensity on T2-weighted (p = 0.006) and diffusion-weighted
      images (p = 0.039) were associated with a better response according to RECIST.
      Post-treatment changes include peritumoral ring-like enhanced changes with high
      intensity on T2-weighted images. CONCLUSIONS: SBRT is a promising technique for
      the treatment of inoperable HCC. Post-treatment changes on MRI images can
      resemble tumor progression and as such must be adequately distinguished. The
      regression of tumorous enhancement is variable over time, although diffusion
      weighted and T2-weighted intensities are predictive factors for tumor RECIST
      responses on subsequent MRIs. They hence provide a way to reliably predict
      treatment responses.

PMID- 28441448
TI  - Development and validation of a modified Korean version of the Pharmacy Services
      Questionnaire (PSQ-K) for the quality assessment of community pharmacy services.
AB  - Patient-reported outcome (PRO) measures and validated instruments have become
      integral in assessing the quality of healthcare delivery, including
      pharmaceutical care services. The Pharmacy Services Questionnaire (PSQ) measures
      patient satisfaction with pharmaceutical care. In this study, we developed a
      modified Korean version of the PSQ (PSQ-K) and evaluated its validity and
      reliability. The PSQ-K was developed using a strict translation and cultural
      adaptation procedure. A validation study was performed in six community
      pharmacies in Korea. A total of 300 respondents completed three questionnaires (a
      brief questionnaire for social demographics and clinical characteristics, the PSQ
      K, and the 5-level EuroQoL Group's 5-dimension [EQ-5D-5L]). Standard validity and
      reliability analyses were performed. The internal consistency of the PSQ-K was
      high for all scales (Cronbach's alpha > 0.9). The PSQ-K indicated good
      discriminant and divergent validity. Known-group comparisons revealed that the
      PSQ-K was able to distinguish between respondents differing in socio-demographic
      characteristics, such as gender, level of education, and household income. In
      conclusion, the PSQ-K is a highly reliable and valid PRO instrument for assessing
      the level of satisfaction with community pharmacy services.

PMID- 28441449
TI  - Effectiveness and safety of mycophenolate mofetil in idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: Currently available antifibrotic treatments may slow down disease
      progression in idiopathic pulmonary fibrosis (IPF), but are associated with
      potentially significant side effects and are costly. Mycophenolate mofetil (MMF)
      is well known for its potent immunosuppressive properties and possesses important
      antiproliferative and antifibrotic effects. The safety and effectiveness of MMF
      in IPF is unknown. METHODS: We performed a retrospective multicohort analysis of
      IPF patients treated with MMF compared to those treated with either
      ineffective/harmful treatments or no treatment. Longitudinal change in forced
      vital capacity (FVC) between the groups was analyzed using a mixed model with
      random intercept and slope allowing for repeated measures within subjects.
      Categorical change in FVC, median overall survival, and adverse events were also
      assessed. RESULTS: Forty-one IPF patients were included: 11 treated with MMF, 20
      treated with ineffective/harmful agents (such as prednisone, azathioprine, and/or
      NAC), and 10 did not receive any specific treatment for their IPF. After one
      year, there was a trend towards reduced FVC decline in the MMF-treated group (
      76.3 mL, -2.4% of predicted) compared to the non-MMF-treated (-165 mL, -8.9% of
      predicted) and the no-treatment (-239 mL, -11.5% of predicted) groups,
      respectively. By categorical change, there was a trend towards greater FVC
      stability in the MMF-treated group (87.5%) compared to the non-MMF-treated (57%)
      and the no-treatment groups (50%), respectively. MMF-treated IPF patients had a
      trend towards improved median overall survival (40.3 months) compared to the non
      MMF-treated (25.5 months) and the no-treatment (29.3 months) groups,
      respectively. Treatment-related adverse events were not different between groups;
      however, very few adverse events were reported overall. CONCLUSIONS: MMF
      treatment was associated with potentially clinically important trends toward
      reduced annual FVC decline (similar to approved antifibrotics), greater FVC
      stability and improved overall survival in IPF patients. MMF was generally safe,
      well tolerated, and relatively inexpensive. Future prospective studies of MMF in
      combination with antifibrotic therapy in IPF are needed.

PMID- 28441451
TI  - Two featured series of rRNA-derived RNA fragments (rRFs) constitute a novel class
      of small RNAs.
AB  - In this study, we reported two featured series of rRNA-derived RNA fragments
      (rRFs) from the small RNA sequencing (sRNA-seq) data of Amblyomma testudinarium
      using the Illunima platform. Two series of rRFs (rRF5 and rRF3) were precisely
      aligned to the 5' and 3' ends of the 5.8S and 28S rRNA gene. The rRF5 and rRF3
      series were significantly more highly expressed than the rRFs located in the body
      of the rRNA genes. These series contained perfectly aligned reads, the lengths of
      which varied progressively with 1-bp differences. The rRF5 and rRF3 series in the
      same expression pattern exist ubiquitously from ticks to human. The cellular
      experiments showed the RNAi knockdown of one 20-nt rRF3 induced the cell
      apoptosis and inhibited the cell proliferation. In addition, the RNAi knockdown
      resulted in a significant decrease of H1299 cells in the G2 phase of the cell
      cycle. These results indicated the rRF5 and rRF3 series were not random
      intermediates or products during rRNA degradation, but could constitute a new
      class of small RNAs that deserves further investigation.

PMID- 28441450
TI  - Commensal bacteria and essential amino acids control food choice behavior and
      reproduction.
AB  - Choosing the right nutrients to consume is essential to health and wellbeing
      across species. However, the factors that influence these decisions are poorly
      understood. This is particularly true for dietary proteins, which are important
      determinants of lifespan and reproduction. We show that in Drosophila
      melanogaster, essential amino acids (eAAs) and the concerted action of the
      commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators
      of food choice. Using a chemically defined diet, we show that the absence of any
      single eAA from the diet is sufficient to elicit specific appetites for amino
      acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the
      lack of dietary eAAs: both increased yeast appetite and decreased reproduction
      induced by eAA deprivation are rescued by the presence of commensals.
      Surprisingly, these effects do not seem to be due to changes in AA titers,
      suggesting that gut bacteria act through a different mechanism to change behavior
      and reproduction. Thus, eAAs and commensal bacteria are potent modulators of
      feeding decisions and reproductive output. This demonstrates how the interaction
      of specific nutrients with the microbiome can shape behavioral decisions and life
      history traits.

PMID- 28441452
TI  - Systematic review finds that study data not published in full text articles have
      unclear impact on meta-analyses results in medical research.
AB  - BACKGROUND: A meta-analysis as part of a systematic review aims to provide a
      thorough, comprehensive and unbiased statistical summary of data from the
      literature. However, relevant study results could be missing from a meta-analysis
      because of selective publication and inadequate dissemination. If missing outcome
      data differ systematically from published ones, a meta-analysis will be biased
      with an inaccurate assessment of the intervention effect. As part of the EU
      funded OPEN project (www.open-project.eu) we conducted a systematic review that
      assessed whether the inclusion of data that were not published at all and/or
      published only in the grey literature influences pooled effect estimates in meta
      analyses and leads to different interpretation. METHODS AND FINDINGS: Systematic
      review of published literature (methodological research projects). Four
      bibliographic databases were searched up to February 2016 without restriction of
      publication year or language. Methodological research projects were considered
      eligible for inclusion if they reviewed a cohort of meta-analyses which (i)
      compared pooled effect estimates of meta-analyses of health care interventions
      according to publication status of data or (ii) examined whether the inclusion of
      unpublished or grey literature data impacts the result of a meta-analysis. Seven
      methodological research projects including 187 meta-analyses comparing pooled
      treatment effect estimates according to different publication status were
      identified. Two research projects showed that published data showed larger pooled
      treatment effects in favour of the intervention than unpublished or grey
      literature data (Ratio of ORs 1.15, 95% CI 1.04-1.28 and 1.34, 95% CI 1.09-1.66).
      In the remaining research projects pooled effect estimates and/or overall
      findings were not significantly changed by the inclusion of unpublished and/or
      grey literature data. The precision of the pooled estimate was increased with
      narrower 95% confidence interval. CONCLUSIONS: Although we may anticipate that
      systematic reviews and meta-analyses not including unpublished or grey literature
      study results are likely to overestimate the treatment effects, current empirical
      research shows that this is only the case in a minority of reviews. Therefore,
      currently, a meta-analyst should particularly consider time, effort and costs
      when adding such data to their analysis. Future research is needed to identify
      which reviews may benefit most from including unpublished or grey data.

PMID- 28441454
TI  - Correction: CD90 and CD24 Co-Expression Is Associated with Pancreatic
      Intraepithelial Neoplasias.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0158021.].

PMID- 28441453
TI  - Brainstem response patterns in deeply-sedated critically-ill patients predict 28
      day mortality.
AB  - BACKGROUND AND PURPOSE: Deep sedation is associated with acute brain dysfunction
      and increased mortality. We had previously shown that early-assessed brainstem
      reflexes may predict outcome in deeply sedated patients. The primary objective
      was to determine whether patterns of brainstem reflexes might predict mortality
      in deeply sedated patients. The secondary objective was to generate a score
      predicting mortality in these patients. METHODS: Observational prospective
      multicenter cohort study of 148 non-brain injured deeply sedated patients,
      defined by a Richmond Assessment sedation Scale (RASS) <-3. Brainstem reflexes
      and Glasgow Coma Scale were assessed within 24 hours of sedation and categorized
      using latent class analysis. The Full Outline Of Unresponsiveness score (FOUR)
      was also assessed. Primary outcome measure was 28-day mortality. A "Brainstem
      Responses Assessment Sedation Score" (BRASS) was generated. RESULTS: Two distinct
      sub-phenotypes referred as homogeneous and heterogeneous brainstem reactivity
      were identified (accounting for respectively 54.6% and 45.4% of patients).
      Homogeneous brainstem reactivity was characterized by preserved reactivity to
      nociceptive stimuli and a partial and topographically homogenous depression of
      brainstem reflexes. Heterogeneous brainstem reactivity was characterized by a
      loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem
      reflexes depression. Heterogeneous sub-phenotype was a predictor of increased
      risk of 28-day mortality after adjustment to Simplified Acute Physiology Score-II
      (SAPS-II) and RASS (Odds Ratio [95% confidence interval] = 6.44 [2.63-15.8];
      p<0.0001) or Sequential Organ Failure Assessment (SOFA) and RASS (OR [95%CI] =
      5.02 [2.01-12.5]; p = 0.0005). The BRASS (and marginally the FOUR) predicted 28
      day mortality (c-index [95%CI] = 0.69 [0.54-0.84] and 0.65 [0.49-0.80]
      respectively). CONCLUSION: In this prospective cohort study, around half of all
      deeply sedated critically ill patients displayed an early particular neurological
      sub-phenotype predicting 28-day mortality, which may reflect a dysfunction of the
      brainstem.

PMID- 28441455
TI  - Gene expression study and pathway analysis of histological subtypes of intestinal
      metaplasia that progress to gastric cancer.
AB  - BACKGROUND: Intestinal metaplasia (IM) is a precursor lesion that precedes
      gastric cancer (GC). There are two IM histological subtypes, complete (CIM) and
      incomplete (IIM), the latter having higher progression rates to GC. This study
      was aimed at analysing gene expression and molecular processes involved in the
      progression from normal mucosa to IM, and also from IM subtypes to GC.
      METHODOLOGY: We used expression data to compare the transcriptome of healthy
      gastric mucosa to that of IM not progressing to GC, and the transcriptome of IM
      subtypes that had progressed to GC to those that did not progress. Some
      deregulated genes were validated and pathway analyses were performed. RESULTS:
      Comparison of IM subtypes that had progressed to GC with those that did not
      progress showed smaller differences in the expression profiles than the
      comparison of IM that did not progress with healthy mucosa. New transcripts
      identified in IM not progressing to GC included TRIM, TMEM, homeobox and
      transporter genes and SNORD116. Comparison to normal mucosa identified non
      tumoral Warburg effect and melatonin degradation as previously unreported
      processes involved in IM. Overexpressed antigen processing is common to both IM
      subtypes progressing to GC, but IIM showed more over-expressed oncogenic genes
      and molecular processes than CIM. CONCLUSIONS: There are greater differences in
      gene expression and molecular processes involved in the progression from normal
      healthy mucosa to IM than from IM to gastric cancer. While antigen processing is
      common in both IM-subtypes progressing to GC, more oncogenic processes are
      observed in the progression of IIM.

PMID- 28441456
TI  - Genome-wide association study of facial morphology reveals novel associations
      with FREM1 and PARK2.
AB  - Several studies have now shown evidence of association between common genetic
      variants and quantitative facial traits in humans. The reported associations
      generally involve simple univariate measures and likely represent only a small
      fraction of the genetic loci influencing facial morphology. In this study, we
      applied factor analysis to a set of 276 facial linear distances derived from 3D
      facial surface images of 2187 unrelated individuals of European ancestry. We
      retained 23 facial factors, which we then tested for genetic associations using a
      genome-wide panel of 10,677,593 single nucleotide polymorphisms (SNPs). In total,
      we identified genome-wide significant (p < 5 * 10-8) associations in three
      regions, including two that are novel: one involving measures of midface height
      at 6q26 within an intron of PARK2 (lead SNP rs9456748; p = 4.99 * 10-8) and
      another involving measures of central upper lip height at 9p22 within FREM1 (lead
      SNP rs72713618; p = 2.02 * 10-8). In both cases, the genetic association was
      stronger with the composite facial factor phenotype than with any of the
      individual linear distances that comprise those factors. While the biological
      role of PARK2 in the craniofacial complex is currently unclear, there is evidence
      from both mouse models and Mendelian syndromes that FREM1 may influence facial
      variation. These results highlight the potential value of data-driven
      multivariate phenotyping for genetic studies of human facial morphology.

PMID- 28441457
TI  - Autophagy contributes to falcarindiol-induced cell death in breast cancer cells
      with enhanced endoplasmic reticulum stress.
AB  - Falcarindiol (FAD) is a natural polyyne have been found in many food and dietary
      plants. It has been found to have various beneficial biological activities. In
      this study, we demonstrated its anticancer function and mechanism in breast
      cancer cells. We found that FAD preferentially induces cell death in breast
      cancer cells. FAD-induced cell death is caspase-dependent. However, FAD induces
      autophagy to contribute to the cell death. Blocking autophagy by either chemical
      inhibitors or genetic knockout of autophagy signaling component inhibits FAD
      induced cell death. We further found that FAD-induced cell death is mediated by
      the induction of endoplasmic reticulum stress. We also identified that FAD has
      synergistic effect with approved cancer drugs 5-FU and Bortezomib in killing
      breast cancer cells. Summarily, these data demonstrate that FAD has strong and
      specific anticancer effect in breast cancer cells, and provide some insights
      about the roles of autophagy in FAD-induced cell death.

PMID- 28441458
TI  - Evidence that promotion of male circumcision did not lead to sexual risk
      compensation in prioritized Sub-Saharan countries.
AB  - BACKGROUND: WHO and UNAIDS prioritized 14 eastern and southern African countries
      with high HIV and low male circumcision prevalence for a voluntary medical male
      circumcision (VMMC) scale-up in 2007. Because circumcision provides only partial
      protection against HIV infection to men, the issue of possible risk compensation
      in response to VMMC campaigns is of particular concern. In this study, we looked
      at population-level survey data from the countries prioritized by WHO for a VMMC
      scale-up. We compared the difference in sexual risk behaviours (SRB) between
      circumcised and uncircumcised men before and after the WHO's official VMMC
      promotion. MATERIALS AND METHODS: Ten countries (Kenya, Lesotho, Malawi,
      Mozambique, Namibia, Rwanda, Tanzania, Uganda, Zambia and Zimbabwe) participating
      in the WHO's VMMC scale-up had available data from the Demographic and Health
      Surveys (DHS). We used cumulative-link mixed models to investigate interactions
      between survey period and circumcision status in predicting SRB, in order to
      evaluate whether the difference between the behavior of the two groups changed
      before and after the scale-up, while controlling for socio-demographic and
      knowledge-related covariates. The main responses were condom use at last sex and
      number of non-cohabiting sexual partners, both in the last 12 months. RESULTS:
      There was little change in condom use by circumcised men relative to
      uncircumcised men from before the VMMC scale up to after the scale up. The
      relative odds ratio is 1.06 (95% CI, 0.95-1.18; interaction P = 0.310).
      Similarly, there was little change in the number of non-cohabiting partners in
      circumcised men (relative to uncircumcised men): the relative odds ratio of
      increasing the number of partners is 0.95 (95% CI, 0.86-1.05; interaction P =
      0.319). Age, religion, education, job, marital status, media use and HIV
      knowledge also showed statistically significant association with the studied risk
      behaviours. We also found significant differences among countries, while
      controlling for covariates. CONCLUSIONS: Overall, we find no evidence of sexual
      risk compensation in response to VMMC campaigns in countries prioritized by WHO.
      Changes in relative partner behaviour and the relative odds of condom use were
      small (and of uncertain sign). In fact, our estimates, though not significant,
      both suggest slightly less risky behavior. We conclude that sexual risk
      compensation in response to VMMC campaigns has not been a serious problem to
      date, but urge continued attention to local context, and to promulgating accurate
      messages about circumcision within and beyond the VMMC context.

PMID- 28441459
TI  - Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver
      disease: A cross-sectional study.
AB  - Cannabis use is associated with reduced prevalence of obesity and diabetes
      mellitus (DM) in humans and mouse disease models. Obesity and DM are a well
      established independent risk factor for non-alcoholic fatty liver disease
      (NAFLD), the most prevalent liver disease globally. The effects of cannabis use
      on NAFLD prevalence in humans remains ill-defined. Our objective is to determine
      the relationship between cannabis use and the prevalence of NAFLD in humans. We
      conducted a population-based case-control study of 5,950,391 patients using the
      2014 Healthcare Cost and Utilization Project (HCUP), Nationwide Inpatient Survey
      (NIS) discharge records of patients 18 years and older. After identifying
      patients with NAFLD (1% of all patients), we next identified three exposure
      groups: non-cannabis users (98.04%), non-dependent cannabis users (1.74%), and
      dependent cannabis users (0.22%). We adjusted for potential demographics and
      patient related confounders and used multivariate logistic regression (SAS 9.4)
      to determine the odds of developing NAFLD with respects to cannabis use. Our
      findings revealed that cannabis users (dependent and non-dependent) showed
      significantly lower NAFLD prevalence compared to non-users (AOR: 0.82[0.76-0.88];
      p<0.0001). The prevalence of NAFLD was 15% lower in non-dependent users (AOR:
      0.85[0.79-0.92]; p<0.0001) and 52% lower in dependent users (AOR: 0.49[0.36
      0.65]; p<0.0001). Among cannabis users, dependent patients had 43% significantly
      lower prevalence of NAFLD compared to non-dependent patients (AOR: 0.57[0.42
      0.77]; p<0.0001). Our observations suggest that cannabis use is associated with
      lower prevalence of NAFLD in patients. These novel findings suggest additional
      molecular mechanistic studies to explore the potential role of cannabis use in
      NAFLD development.

PMID- 28441460
TI  - How embarrassing! The behavioral and neural correlates of processing social norm
      violations.
AB  - Social norms are important for human social interactions, and violations of these
      norms are evaluated partly on the intention of the actor. Here, we describe the
      revised Social Norm Processing Task (SNPT-R), a paradigm enabling the study of
      behavioral and neural responses to intended and unintended social norm violations
      among both adults and adolescents. We investigated how participants (adolescents
      and adults, n = 87) rate intentional and unintentional social norm violations
      with respect to inappropriateness and embarrassment, and we examined the brain
      activation patterns underlying the processing of these transgressions in an
      independent sample of 21 adults using functional Magnetic Resonance Imaging
      (fMRI). We hypothesized to find activation within the medial prefrontal cortex,
      temporo-parietal cortex and orbitofrontal cortex in response to both intentional
      and unintentional social norm violations, with more pronounced activation for the
      intentional social norm violations in these regions and in the amygdala.
      Participants' ratings confirmed the hypothesis that the three types of stories
      are evaluated differently with respect to intentionality: intentional social norm
      violations were rated as the most inappropriate and most embarrassing.
      Furthermore, fMRI results showed that reading stories on intentional and
      unintentional social norm violations evoked activation within the frontal pole,
      the paracingulate gyrus and the superior frontal gyrus. In addition, processing
      unintentional social norm violations was associated with activation in, among
      others, the orbitofrontal cortex, middle frontal gyrus and superior parietal
      lobule, while reading intentional social norm violations was related to
      activation in the left amygdala. These regions have been previously implicated in
      thinking about one's self, thinking about others and moral reasoning. Together,
      these findings indicate that the SNPT-R could serve as a useful paradigm for
      examining social norm processing, both at the behavioral and the neural level.

PMID- 28441461
TI  - Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces
      ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles.
AB  - OBJECTIVE: To evaluate pregnancy outcomes and the incidence of ovarian
      hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger
      oocyte maturity and establish a threshold level of serum b-hCG associated with
      optimal oocyte maturity. DESIGN: Retrospective cohort. SETTING: Academic medical
      center. PATIENTS: Fresh IVF cycles from 9/2004-12/2011. INTERVENTION: 10,427
      fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to
      E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual
      trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was
      assessed according to dose and BMI. MAIN OUTCOME MEASURES: Oocyte maturity was
      analyzed according to post-trigger serum b-hCG. Fertilization, clinical
      pregnancy, live birth and OHSS rates were examined by hCG trigger dose. RESULTS:
      Post-trigger serum b-hCG 20-30, 30-40, and 40-50 mIU/mL was associated with
      reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs.
      78.9%, respectively, P<0.05). b-hCG 20-50 mIU/mL was associated with a 40.1%
      reduction in live birth (OR 0.59, 95% CI 0.41-0.87). No differences in IVF
      outcomes per retrieval were seen for varying doses of hCG or dual trigger when
      controlling for patient age. The incidence of moderate to severe OHSS was 0.13%
      (n = 14) and severe OHSS was 0.03% (n = 4) of cycles. CONCLUSIONS: Moderate
      stimulation with sliding scale hCG at trigger and fresh transfer is associated
      with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU
      alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity.

PMID- 28441462
TI  - Transcriptomic profiling of a chicken lung epithelial cell line (CLEC213) reveals
      a mitochondrial respiratory chain activity boost during influenza virus
      infection.
AB  - Avian Influenza virus (AIV) is a major concern for the global poultry industry.
      Since 2012, several countries have reported AIV outbreaks among domestic poultry.
      These outbreaks had tremendous impact on poultry production and socio-economic
      repercussion on farmers. In addition, the constant emergence of highly pathogenic
      AIV also poses a significant risk to human health. In this study, we used a
      chicken lung epithelial cell line (CLEC213) to gain a better understanding of the
      molecular consequences of low pathogenic AIV infection in their natural host.
      Using a transcriptome profiling approach based on microarrays, we identified a
      cluster of mitochondrial genes highly induced during the infection.
      Interestingly, most of the regulated genes are encoded by the mitochondrial
      genome and are involved in the oxidative phosphorylation metabolic pathway. The
      biological consequences of this transcriptomic induction result in a 2.5- to 4
      fold increase of the ATP concentration within the infected cells. PB1-F2, a viral
      protein that targets the mitochondria was not found associated to the boost of
      activity of the respiratory chain. We next explored the possibility that ATP may
      act as a host-derived danger signal (through production of extracellular ATP) or
      as a boost to increase AIV replication. We observed that, despite the activation
      of the P2X7 purinergic receptor pathway, a 1mM ATP addition in the cell culture
      medium had no effect on the virus replication in our epithelial cell model.
      Finally, we found that oligomycin, a drug that inhibits the oxidative
      phosphorylation process, drastically reduced the AIV replication in CLEC213
      cells, without apparent cellular toxicity. Collectively, our results suggest that
      AIV is able to boost the metabolic capacities of its avian host in order to
      provide the important energy needs required to produce progeny virus.

PMID- 28441463
TI  - RAPIDSNPs: A new computational pipeline for rapidly identifying key genetic
      variants reveals previously unidentified SNPs that are significantly associated
      with individual platelet responses.
AB  - Advances in omics technologies have led to the discovery of genetic markers, or
      single nucleotide polymorphisms (SNPs), that are associated with particular
      diseases or complex traits. Although there have been significant improvements in
      the approaches used to analyse associations of SNPs with disease, further
      optimised and rapid techniques are needed to keep up with the rate of SNP
      discovery, which has exacerbated the 'missing heritability' problem. Here, we
      have devised a novel, integrated, heuristic-based, hybrid analytical
      computational pipeline, for rapidly detecting novel or key genetic variants that
      are associated with diseases or complex traits. Our pipeline is particularly
      useful in genetic association studies where the genotyped SNP data are highly
      dimensional, and the complex trait phenotype involved is continuous. In
      particular, the pipeline is more efficient for investigating small sets of
      genotyped SNPs defined in high dimensional spaces that may be associated with
      continuous phenotypes, rather than for the investigation of whole genome
      variants. The pipeline, which employs a consensus approach based on the random
      forest, was able to rapidly identify previously unseen key SNPs, that are
      significantly associated with the platelet response phenotype, which was used as
      our complex trait case study. Several of these SNPs, such as rs6141803 of COMMD7
      and rs41316468 in PKT2B, have independently confirmed associations with
      cardiovascular diseases (CVDs) according to other unrelated studies, suggesting
      that our pipeline is robust in identifying key genetic variants. Our new pipeline
      provides an important step towards addressing the problem of 'missing
      heritability' through enhanced detection of key genetic variants (SNPs) that are
      associated with continuous complex traits/disease phenotypes.

PMID- 28441464
TI  - Crucial roles of Pox neuro in the developing ellipsoid body and antennal lobes of
      the Drosophila brain.
AB  - The paired box gene Pox neuro (Poxn) is expressed in two bilaterally symmetric
      neuronal clusters of the developing adult Drosophila brain, a protocerebral
      dorsal cluster (DC) and a deutocerebral ventral cluster (VC). We show that all
      cells that express Poxn in the developing brain are postmitotic neurons. During
      embryogenesis, the DC and VC consist of only 20 and 12 neurons that express Poxn,
      designated embryonic Poxn-neurons. The number of Poxn-neurons increases only
      during the third larval instar, when the DC and VC increase dramatically to about
      242 and 109 Poxn-neurons, respectively, virtually all of which survive to the
      adult stage, while no new Poxn-neurons are added during metamorphosis. Although
      the vast majority of Poxn-neurons express Poxn only during third instar, about
      half of them are born by the end of embryogenesis, as demonstrated by the absence
      of BrdU incorporation during larval stages. At late third instar, embryonic Poxn
      neurons, which begin to express Poxn during embryogenesis, can be easily
      distinguished from embryonic-born and larval-born Poxn-neurons, which begin to
      express Poxn only during third instar, (i) by the absence of Pros, (ii) their
      overt differentiation of axons and neurites, and (iii) the strikingly larger
      diameter of their cell bodies still apparent in the adult brain. The embryonic
      Poxn-neurons are primary neurons that lay out the pioneering tracts for the
      secondary Poxn-neurons, which differentiate projections and axons that follow
      those of the primary neurons during metamorphosis. The DC and the VC participate
      only in two neuropils of the adult brain. The DC forms most, if not all, of the
      neurons that connect the bulb (lateral triangle) with the ellipsoid body, a
      prominent neuropil of the central complex, while the VC forms most of the ventral
      projection neurons of the antennal lobe, which connect it ipsilaterally to the
      lateral horn, bypassing the mushroom bodies. In addition, Poxn-neurons of the VC
      are ventral local interneurons of the antennal lobe. In the absence of Poxn
      protein in the developing brain, embryonic Poxn-neurons stall their projections
      and cannot find their proper target neuropils, the bulb and ellipsoid body in the
      case of the DC, or the antennal lobe and lateral horn in the case of the VC,
      whereby the absence of the ellipsoid body neuropil is particularly striking. Poxn
      is thus crucial for pathfinding both in the DC and VC. Additional implications of
      our results are discussed.

PMID- 28441465
TI  - Gender differences in care-seeking behavior and healthcare consumption
      immediately after whiplash trauma.
AB  - OBJECTIVE: The aim was to study gender differences in care-seeking behavior and
      treatment provided immediately after whiplash trauma. METHODS: Participants were
      residents from a defined geographical area, Skaraborg County in the southwestern
      part of Sweden. A cohort of 3,368 persons exposed to whiplash trauma and
      attending a healthcare facility immediately after the trauma between 1999 and
      2008 were identified in a database. Information about gender, age, time elapsed
      prior to seeking care, type of healthcare contact, initial treatment provided and
      eventual hospitalization time was retrieved. RESULTS: Women sought care later
      than men (p = 0.00074). Women consulted primary healthcare first more often than
      men, who more often first sought hospital care (p = 0.0060). There were no gender
      differences regarding the type of treatment after trauma. Women had longer
      hospital admission than men (p = 0.022), indicating their injuries were at least
      similar to or worse than men's. CONCLUSION: Women sought healthcare later than
      men after whiplash trauma. Although not directly investigated in this study, it
      raises the question if this may reduce their probability of getting financial
      compensation compared to men.

PMID- 28441466
TI  - Biomonitoring of marine vertebrates in Monterey Bay using eDNA metabarcoding.
AB  - Molecular analysis of environmental DNA (eDNA) can be used to assess vertebrate
      biodiversity in aquatic systems, but limited work has applied eDNA technologies
      to marine waters. Further, there is limited understanding of the spatial
      distribution of vertebrate eDNA in marine waters. Here, we use an eDNA
      metabarcoding approach to target and amplify a hypervariable region of the
      mitochondrial 12S rRNA gene to characterize vertebrate communities at 10
      oceanographic stations spanning 45 km within the Monterey Bay National Marine
      Sanctuary (MBNMS). In this study, we collected three biological replicates of
      small volume water samples (1 L) at 2 depths at each of the 10 stations. We
      amplified fish mitochondrial DNA using a universal primer set. We obtained
      5,644,299 high quality Illumina sequence reads from the environmental samples.
      The sequence reads were annotated to the lowest taxonomic assignment using a
      bioinformatics pipeline. The eDNA survey identified, to the lowest taxonomic
      rank, 7 families, 3 subfamilies, 10 genera, and 72 species of vertebrates at the
      study sites. These 92 distinct taxa come from 33 unique marine vertebrate
      families. We observed significantly different vertebrate community composition
      between sampling depths (0 m and 20/40 m deep) across all stations and
      significantly different communities at stations located on the continental shelf
      (<200 m bottom depth) versus in the deeper waters of the canyons of Monterey Bay
      (>200 m bottom depth). All but 1 family identified using eDNA metabarcoding is
      known to occur in MBNMS. The study informs the implementation of eDNA
      metabarcoding for vertebrate biomonitoring.

PMID- 28441467
TI  - Distribution of mammal functional diversity in the Neotropical realm: Influence
      of land-use and extinction risk.
AB  - Functional diversity represents a measure of diversity that incorporates the role
      of species in an ecosystem, and therefore its dynamics and resilience. Assessing
      its drivers and spatial variation represents an important step forward in our
      understanding of functional ecosystem dynamics and it is also necessary to
      achieve a comprehensive conservation planning. In this paper, we assessed mammal
      functional diversity for the 218 ecoregions within the Neotropical realm. We
      evaluated the overall influence and spatial variation of species richness,
      ecoregion extent, intervention and species at risk on functional diversity. Using
      ordinary least squares and geographically weighted regression modeling
      approaches, we found that intervened areas and threatened and non-threatened
      species are the most influential overall drivers of functional diversity.
      However, we also detected that these variables do not operate equally across
      scales. Our local analyses indicated both that the variation explained and local
      coefficients vary spatially depending on the ecoregion and major habitat type. As
      estimates of functional diversity are based on current distribution of all
      mammals, negative influence of intervened areas and positive influence of non
      threatened species may reflect a potential degradation of functional processes
      for some ecosystems. Most generally, the negative influence of intervention
      together with the influence of threatened species indicates that some areas are
      currently more susceptible to functional diversity loss. Our results help to
      pinpoint key areas requiring urgent conservation action to reduce natural land
      cover loss and areas where threatened species play influential roles on ecosystem
      functioning.

PMID- 28441468
TI  - Histological study of white rhinoceros integument.
AB  - In this study, we report findings from a microscopic analysis of the white
      rhinoceros (Ceratotherium simum) integumentary ultrastructure. Skin samples from
      the cheek, shoulder, flank and rump were taken from a 46-year-old female southern
      white rhinoceros and examined using H&E and elastic histological stains. The
      epidermis was thickest in the flank (1.003 mm) followed by the rump, cheek and
      shoulder. The stratum corneum comprised more than half the epidermal thickness.
      Numerous melanin granules were found in the basal and spinosum layers. The
      epidermal-dermal junction was characterized by abundant papillary folds
      increasing surface contact between integument layers. Most of the dermal
      thickness consisted of organized collagen bundles with scattered elastic fibers.
      Collagen fiber bundles were thickest in the flank (210.9 MUm) followed by
      shoulder, rump and cheek. Simple coiled sweat glands were present in the dermis,
      but hair and sebaceous glands were absent. Together, these data suggest the white
      rhinoceros has a unique integumentary system among large terrestrial herbivores.

PMID- 28441469
TI  - The Effect of Ar/O2 and H2O Plasma Treatment of SnO2 Nanoparticles and Nanowires
      on Carbon Monoxide and Benzene Detection.
AB  - As the final piece of a broader study on structure-property performance of SnO2
      sensors, this study examines the performance of sensors created from tin(IV)
      oxide (SnO2) nanowires and nanoparticles as a function of temperature for
      untreated (UT) devices as well as those treated using Ar/O2 and H2O plasmas.
      Nanoparticle and nanowire sensors were exposed to air, carbon monoxide (CO), or
      benzene (C6H6) to determine sensor response (Rair/Rgas) and sensitivity
      (Rair/Rgas > 1 or Rgas/Rair > 1). Although both Ar/O2 and H2O plasma modification
      minimally increase sensor sensitivity toward CO and C6H6 under most conditions,
      this study explores initial plasma parameters of a wide array of plasma
      precursors to better understand the materials properties and gas-phase species
      that lead to specific sensing capabilities. In particular, certain Ar/O2 and H2O
      plasma treatment conditions resulted in increased sensitivity over UT
      nanomaterials at 25 and 50  degrees C, but of greatest importance is the
      knowledge gained from the combined materials, gas-phase, and sensor performance
      analysis that provide greater insight for effectively selecting future materials
      and modification systems to achieve optimal gas sensor performance.

PMID- 28441470
TI  - Al2O3 and SiO2 Atomic Layer Deposition Layers on ZnO Photoanodes and Degradation
      Mechanisms.
AB  - Strategies for protecting unstable semiconductors include the utilization of
      surface layers composed of thin films deposited using atomic layer deposition
      (ALD). The protective layer is expected to (1) be stable against reaction with
      photogenerated holes, (2) prevent direct contact of the unstable semiconductor
      with the electrolyte, and (3) prevent the migration of ions through the
      semiconductor/electrolyte interface, while still allowing photogenerated carriers
      to transport to the interface and participate in the desired redox reactions.
      Zinc oxide (ZnO) is an attractive photocatalyst material due to its high
      absorption coefficient and high carrier mobilities. However, ZnO is chemically
      unstable and undergoes photocorrosion, which limits its use in applications such
      as in photoelectrochemical cells for water splitting or photocatalytic water
      purification. This article describes an investigation of the band alignment,
      electrochemical properties, and interfacial structure of ZnO coated with Al2O3
      and SiO2 ALD layers. The interface electronic properties were determined using in
      situ X-ray and UV photoemission spectroscopy, and the photochemical response and
      stability under voltage bias were determined using linear sweep voltammetry and
      chronoamperometry. The resulting surface structure and degradation processes were
      identified using atomic force, scanning electron, and transmission electron
      microscopy. The suite of characterization tools enable the failure mechanisms to
      be more clearly discerned. The results show that the rapid photocorrosion of ZnO
      thin films is only slightly slowed by use of an Al2O3 ALD coating. A 4 nm SiO2
      layer proved to be more effective, but its protection capability could be
      affected by the diffusion of ions from the electrolyte.

PMID- 28441471
TI  - Gemcitabine Integrated Nano-Prodrug Carrier System.
AB  - Peptide nanomaterials have received a great deal of interest in drug-delivery
      applications due to their biodegradability, biocompatibility, suitability for
      large-scale synthesis, high drug-loading capacities, targeting ability, and
      ordered structural organization. The covalent conjugation of drugs to peptide
      backbones results in prolonged circulation time and improved stability of drugs.
      Therapeutic efficacy of gemcitabine, which is used for breast cancer treatment,
      is severely compromised due to its rapid plasma degradation. Its hydrophilic
      nature poses a challenge for both its efficient encapsulation into nanocarrier
      systems and its sustained release property. Here, we designed a new peptide
      prodrug molecule for the anticancer drug gemcitabine, which was covalently
      conjugated to the C-terminal of 9-fluorenylmethoxy carbonyl (Fmoc)-protected
      glycine. The prodrug was further integrated into peptide nanocarrier system
      through noncovalent interactions. A pair of oppositely charged amyloid-inspired
      peptides (Fmoc-AIPs) were exploited as components of the drug-carrier system and
      self-assembled into one-dimensional nanofibers at physiological conditions. The
      gemcitabine integrated nanoprodrug carrier system exhibited slow release and
      reduced the cellular viability of 4T1 breast cancer cell line in a time- and
      concentration-dependent manner.

PMID- 28441472
TI  - Repurposing a Two-Component System-Based Biosensor for the Killing of Vibrio
      cholerae.
AB  - New strategies to control cholera are urgently needed. This study develops an in
      vitro proof-of-concept sense-and-kill system in a wild-type Escherichia coli
      strain to target the causative pathogen Vibrio cholerae using a synthetic biology
      approach. Our engineered E. coli specifically detects V. cholerae via its quorum
      sensing molecule CAI-1 and responds by expressing the lysis protein YebF-Art-085,
      thereby self-lysing to release the killing protein Art-085 to kill V. cholerae.
      For this report, we individually characterized YebF-Art-085 and Art-085
      expression and their activities when coupled to our previously developed V.
      cholerae biosensing circuit. We show that, in the presence of V. cholerae
      supernatant, the final integrated sense-and-kill system in our engineered E. coli
      can effectively inhibit the growth of V. cholerae cells. This work represents the
      first step toward a novel probiotic treatment modality that could potentially
      prevent and treat cholera in the future.

PMID- 28441473
TI  - Assembly of Macrocycle Dye Derivatives into Particles for Fluorescence and
      Photoacoustic Applications.
AB  - Optical imaging is a rapidly progressing medical technique that can benefit from
      the development of new and improved optical imaging agents suitable for use in
      vivo. However, the molecular rules detailing what optical agents can be processed
      and encapsulated into in vivo presentable forms are not known. We here present
      the screening of series of highly hydrophobic porphyrin, phthalocyanine, and
      naphthalocyanine dye macrocycles through a self-assembling Flash
      NanoPrecipitation process to form a series of water dispersible dye nanoparticles
      (NPs). Ten out of 19 tested dyes could be formed into poly(ethylene glycol)
      coated nanoparticles 60-150 nm in size, and these results shed insight on dye
      structural criteria that are required to permit dye assembly into NPs. Dye NPs
      display a diverse range of absorbance profiles with absorbance maxima within the
      NIR region, and have absorbance that can be tuned by varying dye choice or by
      doping bulking materials in the NP core. Particle properties such as dye core
      load and the compositions of co-core dopants were varied, and subsequent effects
      on photoacoustic and fluorescence signal intensities were measured. These results
      provide guidelines for designing NPs optimized for photoacoustic imaging and NPs
      optimized for fluorescence imaging. This work provides important details for dye
      NP engineering, and expands the optical imaging tools available for use.

PMID- 28441474
TI  - Dendrimer-Modified MoS2 Nanoflakes as a Platform for Combinational Gene Silencing
      and Photothermal Therapy of Tumors.
AB  - Exploitation of novel hybrid nanomaterials for combinational tumor therapy is
      challenging. In this work, we synthesized dendrimer-modified MoS2 nanoflakes for
      combinational gene silencing and photothermal therapy (PTT) of cancer cells.
      Hydrothermally synthesized MoS2 nanoflakes were modified with generation 5 (G5)
      poly(amidoamine) dendrimers partially functionalized with lipoic acid via
      disulfide bond. The formed G5-MoS2 nanoflakes display good colloidal stability
      and superior photothermal conversion efficiency and photothermal stability. With
      the dendrimer surface amines on their surface, the G5-MoS2 nanoflakes are capable
      of delivering Bcl-2 (B-cell lymphoma-2) siRNA to cancer cells (4T1 cells, a mouse
      breast cancer cells) with excellent transfection efficiency, inducing 47.3% of
      Bcl-2 protein expression inhibition. In vitro cell viability assay data show that
      cells treated with the G5-MoS2/Bcl-2 siRNA polyplexes under laser irradiation
      have a viability of 21.0%, which is much lower than other groups of single mode
      PTT treatment (45.8%) or single mode of gene therapy (68.7%). Moreover, the super
      efficacy of combinational therapy was further demonstrated by treating a
      xenografted 4T1 tumor model in vivo. These results suggest that the synthesized
      G5-MoS2 nanoflakes may be employed as a potential nanoplatform for combinational
      gene silencing and PTT of tumors.

PMID- 28441475
TI  - 2,2'-Spirobis[chromene] Derivatives Chemistry and Their Relation with the
      Multistate System of Anthocyanins.
AB  - The chemistry of 2,2'-spirobis[chromene] derivatives is intimately related to the
      one of anthocyanins and similar compounds. The 2,2'-spirobis[chromene] species
      plays a central role in the network of chemical reactions connecting two
      different flavylium-based multistate systems. In the present work, a new
      asymmetric 2,2'-spirobis[chromene] intermediate possessing a constrained
      propylenic bridge between carbons 3 and 3' was isolated and its role as a pivot
      in the anthocyanins-type multistate of chemical reactions was investigated by the
      conjugation of absorption spectroscopy, stopped-flow, NMR, and X-ray
      crystallography. It was confirmed that the propylenic bridge is essential to
      stabilize the spirobis[chromene] species. Furthermore, under acidic conditions,
      two cis-trans styrylflavylium isomers were identified, which could be
      interconverted directly into one another with light. This is the first report of
      styrylflavylium cations with photoisomerization on the styryl moiety.

PMID- 28441476
TI  - SBOLDesigner 2: An Intuitive Tool for Structural Genetic Design.
AB  - As the Synthetic Biology Open Language (SBOL) data and visual standards gain
      acceptance for describing genetic designs in a detailed and reproducible way,
      there is an increasing need for an intuitive sequence editor tool that biologists
      can use that supports these standards. This paper describes SBOLDesigner 2, a
      genetic design automation (GDA) tool that natively supports both the SBOL data
      model (Version 2) and SBOL Visual (Version 1). This software is enabled to fetch
      and store parts and designs from SBOL repositories, such as SynBioHub. It can
      also import and export data about parts and designs in FASTA, GenBank, and SBOL 1
      data format. Finally, it possesses a simple and intuitive user interface. This
      paper describes the design process using SBOLDesigner 2, highlighting new
      features over the earlier prototype versions. SBOLDesigner 2 is released freely
      and open source under the Apache 2.0 license.

PMID- 28441477
TI  - Local Electron Correlation Treatment in Extended Multireference Calculations:
      Effect of Acceptor-Donor Substituents on the Biradical Character of the
      Polycyclic Aromatic Hydrocarbon Heptazethrene.
AB  - The implementation of a local correlation (LC) treatment of multireference (MR)
      configuration interaction approaches within the COLUMBUS program system is
      reported. The LC treatment is based on the weak pairs approximation of Saebo and
      Pulay (Ann. Rev. Phys. Chem. 1993, 44, 213) and a geometrical analysis of Walter
      et al. (Chem. Phys. Lett. 2001, 346, 177). The removal of simultaneous single
      excitations out of the weak pairs is based on the reference doubly occupied space
      only, leading to a straightforward program implementation and a conceptual
      simplicity in terms of well-defined localized orbitals. Reductions of up to an
      order of magnitude in the configuration space expansion and in computer time for
      the Davidson diagonalization step are found. The selection of the active and the
      virtual orbital spaces is not affected by this procedure. This treatment is
      successfully applied to the singlet biradical heptazethrene and its different
      acceptor-donor substituents: 4,12-dicyanoheptazethrene, 4,12
      diaminoheptazethrene, and 4-amino-12-cyanoheptazethrene. Simultaneous insertion
      of pairs of donor and acceptor groups increases the biradical character; for push
      pull substitution, this effect is significantly smaller. In addition, results
      obtained from spin-corrected unrestricted density functional theory calculations
      are supported by our MR calculations.

PMID- 28441478
TI  - Energy-Transfer Kinetics Driven by Midinfrared Amplified Spontaneous Emission
      after Two-Photon Excitation from Xe (s0) to the Xe (6p[1/2]0) State.
AB  - In optically pumped laser systems, rare gas lasers (RGLs) are a field of great
      interest for researchers. Gas laser regimes with metastable Ne, Ar, and Kr atoms
      have been investigated, while studies of RGLs based on metastable Xe are sparse.
      In this work, when a strong excitation laser (2.92 mJ/pulse, 7.44 * 105 W/cm2)
      was applied to excite Xe atoms from the ground state to the 6p[1/2]0 state, an
      interesting phenomenon emerged: An intense fluorescence of 980 nm (6p[1/2]1
      6s[3/2]2) was produced. However, when the energy of excitation laser was
      decreased to 0.50 mJ/pulse (1.27 * 105 W/cm2), the fluorescence of 980 nm became
      very weak. Besides, lifetime and decay rate constant of the 6p[1/2]0 state under
      the condition of E = 2.92 mJ are significantly different from either those
      measured by other groups or those of E = 0.50 mJ. These phenomena indicate that
      the high energy of excitation laser should trigger some new kinetic mechanisms.
      Further works identified that the new kinetic mechanism is the MIR ASE of 3408 nm
      (6p[1/2]0-6s'[1/2]1). The mechanisms are proposed as follows. Substantial
      6p[1/2]0 atoms are produced by laser excitation. Then, the ASE of 3408 nm
      (6p[1/2]0-6s'[1/2]1) is quickly produced to populate substantial 6s'[1/2]1 atoms.
      The 6s'[1/2]1 atoms can readily arrive at the 6p[1/2]1 states through collision
      by virtue of the small energy difference (84 cm-1) and high collision rate
      constant of the transition from the 6s'[1/2]1 state to the 6p[1/2]1 state. As a
      result, the intense fluorescence of 980 nm is generated.

PMID- 28441479
TI  - Theoretical Study of Low-Lying Omega Electronic States of PtH and PtH.
AB  - Potential energy curves of 65 and 147 low-lying Omega states of PtH and PtH+ are
      respectively constructed using the multireference configuration interaction with
      singles, doubles, and Davidson's cluster corrections (MRCISD+Q), and the spin
      orbit coupling effects are considered through the state-interaction approach with
      relativistic effective core potential spin-orbit operators. Spectroscopic
      constants fitted from these curves are reported and are compared with the
      available experimental or theoretical values. With the aid of the theoretical
      results including transition dipole moments, some experimentally reported
      electronic states and spectral bands of PtH are analyzed and reassigned. This
      work provides useful reference data for future experimental and theoretical
      studies of PtH and PtH+.

PMID- 28441480
TI  - Metabolite Profiling of a Zinc-Accumulating Rice Mutant.
AB  - Breeding crops with high zinc (Zn) density is an effective way to alleviate human
      dietary Zn deficiencies. We characterized a mutant Lilizhi (LLZ) accumulating at
      least 35% higher Zn concentration in grain than the wild type (WT) in hydroponic
      experiments. The mutant stored less Zn content in the root and transported more
      Zn to the grain. Metabolite profiling demonstrated that, with high Zn treatment,
      the contents of proline, asparagine, citric acid, and malic acid were enhanced in
      both LLZ and the WT, which were thought to be involved in Zn transport in rice.
      Furthermore, the contents of cysteine, allothreonine, alanine, tyrosine,
      homoserine, beta-alanine, and nicotianamine required for the production of many
      metal-binding proteins were specifically increased in LLZ. LLZ had higher
      capability of amino acid biosynthesis and metal cation transportation. The
      current research extends our understanding on the physiological mechanisms of Zn
      uploading into grain and provides references for further Zn biofortification
      breeding in rice.

PMID- 28441481
TI  - Best Practices of Computer-Aided Drug Discovery: Lessons Learned from the
      Development of a Preclinical Candidate for Prostate Cancer with a New Mechanism
      of Action.
AB  - Small-molecule drug design is a complex and iterative decision-making process
      relying on pre-existing knowledge and driven by experimental data. Low-molecular
      weight chemicals represent an attractive therapeutic option, as they are readily
      accessible to organic synthesis and can easily be characterized.1 Their potency
      as well as pharmacokinetic and pharmacodynamic properties can be systematically
      and rationally investigated and ultimately optimized via expert science behind
      medicinal chemistry and methods of computer-aided drug design (CADD). In recent
      years, significant advances in molecular modeling techniques have afforded a
      variety of tools to effectively identify potential binding pockets on prospective
      targets, to map key interactions between ligands and their binding sites, to
      construct and assess energetics of the resulting complexes, to predict ADMET
      properties of candidate compounds, and to systematically analyze experimental and
      computational data to derive meaningful structure-activity relationships leading
      to the creation of a drug candidate. This Perspective describes a real case of a
      drug discovery campaign accomplished in a relatively short time with limited
      resources. The study integrated an arsenal of available molecular modeling
      techniques with an array of experimental tools to successfully develop a novel
      class of potent and selective androgen receptor inhibitors with a novel mode of
      action. It resulted in the largest academic licensing deal in Canadian history,
      totaling $142M. This project exemplifies the importance of team science, an
      integrative approach to drug discovery, and the use of best practices in CADD. We
      posit that the lessons learned and best practices for executing an effective CADD
      project can be applied, with similar success, to many drug discovery projects in
      both academia and industry.

PMID- 28441482
TI  - Value of NMR Parameters and DFT Calculations for Quantum Information Processing
      Utilizing Phosphorus Heterocycles.
AB  - Quantum computing is the field of science that uses quantum-mechanical phenomena,
      such as superposition and entanglement, to perform operations on data. The
      fundamental information unit used in quantum computing is the quantum bit or
      qubit. It is well-known that quantum computers could theoretically be able to
      solve problems much more quickly than any classical computers. Currently, the
      first and still the most successful implementations of quantum information
      processing (QIP) have been based on nuclear spins in liquids. However, molecules
      that enable many qubits NMR QIP implementations should meet some conditions: have
      large chemical shifts and be appropriately dispersed for qubit addressability,
      appreciable spin-spin coupling between any pair of spins, and a long relaxation
      time. In this line, benzyldene-2,3-dihydro-1H-[1,3]diphosphole (BDF) derivatives
      have been theoretically tested for maximizing large chemical shifts, spin-spin
      coupling, and minimizing the hyperfine coupling constant. Thus, the structures
      were optimized at the B3LYP/6-311G(d,p) level and showed a significant similarity
      with the experimental geometrical parameters. The NMR spectroscopic parameters
      (delta and J) were calculated with six different DFT functionals. The tau-HCTH/6
      31G(2d) level is in better agreement with the experimental data of 31P and 13C
      chemical shifts, while PCM-B3LYP/cc-pVDZ level shows a decrease on deviation
      between calculated and experimental values for P-P and P-C SSCC. The surface
      response technique was employed to rationalize how the hyperfine constant varies
      with the chemical shifts and coupling constants values. From our findings, BDF
      NO2 was the best candidate for NMR quantum computations (NMR-QC) among the
      studied series.

PMID- 28441483
TI  - Discovery of a Novel Class of Survival Motor Neuron 2 Splicing Modifiers for the
      Treatment of Spinal Muscular Atrophy.
AB  - Spinal muscular atrophy (SMA) is caused by mutation or deletion of the survival
      motor neuron 1 (SMN1) gene, resulting in low levels of functional SMN protein. We
      have reported recently the identification of small molecules (coumarins, iso
      coumarins and pyrido-pyrimidinones) that modify the alternative splicing of SMN2,
      a paralogous gene to SMN1, restoring the survival motor neuron (SMN) protein
      level in mouse models of SMA. Herein, we report our efforts to identify a novel
      chemotype as one strategy to potentially circumvent safety concerns from earlier
      derivatives such as in vitro phototoxicity and in vitro mutagenicity associated
      with compounds 1 and 2 or the in vivo retinal findings observed in a long-term
      chronic tox study with 3 at high exposures only. Optimized representative
      compounds modify the alternative splicing of SMN2, increase the production of
      full length SMN2 mRNA, and therefore levels of full length SMN protein upon oral
      administration in two mouse models of SMA.

PMID- 28441484
TI  - Fully Quantum Description of the Zundel Ion: Combining Variational Quantum Monte
      Carlo with Path Integral Langevin Dynamics.
AB  - We introduce a novel approach for a fully quantum description of coupled electron
      ion systems from first principles. It combines the variational quantum Monte
      Carlo solution of the electronic part with the path integral formalism for the
      quantum nuclear dynamics. On the one hand, the path integral molecular dynamics
      includes nuclear quantum effects by adding a set of fictitious classical
      particles (beads) aimed at reproducing nuclear quantum fluctuations via a
      harmonic kinetic term. On the other hand, variational quantum Monte Carlo can
      provide Born-Oppenheimer potential energy surfaces with a precision comparable to
      the most-advanced post-Hartree-Fock approaches, and with a favorable scaling with
      the system size. In order to cope with the intrinsic noise due to the stochastic
      nature of quantum Monte Carlo methods, we generalize the path integral molecular
      dynamics using a Langevin thermostat correlated according to the covariance
      matrix of quantum Monte Carlo nuclear forces. The variational parameters of the
      quantum Monte Carlo wave function are evolved during the nuclear dynamics, such
      that the Born-Oppenheimer potential energy surface is unbiased. Statistical
      errors on the wave function parameters are reduced by resorting to bead grouping
      average, which we show to be accurate and well-controlled. Our general algorithm
      relies on a Trotter breakup between the dynamics driven by ionic forces and the
      one set by the harmonic interbead couplings. The latter is exactly integrated,
      even in the presence of the Langevin thermostat, thanks to the mapping onto an
      Ornstein-Uhlenbeck process. This framework turns out to be also very efficient in
      the case of noiseless (deterministic) ionic forces. The new implementation is
      validated on the Zundel ion (H5O2+) by direct comparison with standard path
      integral Langevin dynamics calculations made with a coupled cluster potential
      energy surface. Nuclear quantum effects are confirmed to be dominant over thermal
      effects well beyond room temperature, giving the excess proton an increased
      mobility by quantum tunneling.

PMID- 28441485
TI  - New Insights into the Reaction Paths of 4-Carboxybenzophenone Triplet with
      Oligopeptides Containing N- and C-Terminal Methionine Residues.
AB  - The oxidation processes of l-Met-(Pro)n-l-Met peptides that contain two Met
      residues located on the N and C termini and separated by a defined number (n = 0
      4) of proline residues were investigated in aqueous solutions using laser flash
      photolysis. The use of such peptides allowed for distance control between the
      sulfur atoms located in the side chains of the Met residues. Interactions between
      side chains of the Met residues were probed by the observation of transients with
      sigma*-type 2c-3e (S?S)+, (S?N)+, and (S?O)+ bonds as well as of alpha
      (alkylthio)alkyl radicals (alphaS). This approach enabled the monitoring, in real
      time, of the efficiency and kinetics of interactions between amino acid chains.
      Such knowledge is important, inter alia, for long-distance electron-transfer (ET)
      processes because amino acid side chains can serve as relay stations. The yields
      of these transients (measured as quantum yields (Phi)) were found to be dependent
      on the number of Pro residues, however, not dependent in a simple way on the
      average distance <rS-S> between sulfur atoms in Met residues. A decrease in the
      yield of the (S?S)+ species with the number of Pro residues occurred at the
      expense of an increase in the yields of intramolecular three electron-bonded
      (S?O)+/(S?N)+ radical cations and alphaS radicals. These observations were
      rationalized by the fact that the time required for adequate overlap of the
      bonding orbitals is a key factor effecting the yield of the (S?S)+ species. The
      time, however, can be controlled not only by the average distance <rS-S> but also
      by the specific geometrical and conformational properties of the peptide
      molecules.

PMID- 28441486
TI  - N-Substituted 3(10H)-Acridones as Visible-Light, Water-Soluble Photocatalysts:
      Aerobic Oxidative Hydroxylation of Arylboronic Acids.
AB  - We disclosed a novel water-soluble photocatalyst that could promote aerobic
      oxidative hydroxylation of arylboronic acids to furnish phenols in excellent
      yields. This transformation uses visible-light irradiation under environmentally
      friendly conditions, that is, water-soluble catalyst, metal-free, green oxidant,
      room temperature.

PMID- 28441487
TI  - The Isomeric Preference of an Atypical Dopamine Transporter Inhibitor Contributes
      to Its Selection of the Transporter Conformation.
AB  - Cocaine, a widely abused psychostimulant, inhibits the dopamine transporter (DAT)
      by trapping the protein in an outward-open conformation, whereas atypical DAT
      inhibitors such as benztropine have low abuse liability and prefer less outward
      open conformations. Here, we use a spectrum of computational modeling and
      simulation approaches to obtain the underlying molecular mechanism in atomistic
      detail. Interestingly, our quantum mechanical calculations and molecular dynamics
      (MD) simulations suggest that a benztropine derivative JHW007 prefers a different
      stereoisomeric conformation of tropane in binding to DAT compared to that of a
      cocaine derivative, CFT. To further investigate the different inhibition
      mechanisms of DAT, we carried out MD simulations in combination with Markov state
      modeling analysis of wild-type and Y156F DAT in the absence of any ligand or the
      presence of CFT or JHW007. Our results indicate that the Y156F mutation and CFT
      shift the conformational equilibrium toward an outward-open conformation, whereas
      JHW007 prefers an inward-occluded conformation. Our findings reveal the
      mechanistic details of DAT inhibition by JHW007 at the atomistic level, which
      provide clues for rational design of atypical inhibitors.

PMID- 28441488
TI  - Formaldehyde (HCHO) As a Hazardous Air Pollutant: Mapping Surface Air
      Concentrations from Satellite and Inferring Cancer Risks in the United States.
AB  - Formaldehyde (HCHO) is the most important carcinogen in outdoor air among the 187
      hazardous air pollutants (HAPs) identified by the U.S. Environmental Protection
      Agency (EPA), not including ozone and particulate matter. However, surface
      observations of HCHO are sparse and the EPA monitoring network could be prone to
      positive interferences. Here we use 2005-2016 summertime HCHO column data from
      the OMI satellite instrument, validated with high-quality aircraft data and
      oversampled on a 5 * 5 km2 grid, to map surface air HCHO concentrations across
      the contiguous U.S. OMI-derived summertime HCHO values are converted to annual
      averages using the GEOS-Chem chemical transport model. Results are in good
      agreement with high-quality summertime observations from urban sites (-2% bias, r
      = 0.95) but a factor of 1.9 lower than annual means from the EPA network. We thus
      estimate that up to 6600-12 500 people in the U.S. will develop cancer over their
      lifetimes by exposure to outdoor HCHO. The main HCHO source in the U.S. is
      atmospheric oxidation of biogenic isoprene, but the corresponding HCHO yield
      decreases as the concentration of nitrogen oxides (NOx = NO + NO2) decreases. A
      GEOS-Chem sensitivity simulation indicates that HCHO levels would decrease by 20
      30% in the absence of U.S. anthropogenic NOx emissions. Thus, NOx emission
      controls to improve ozone air quality have a significant cobenefit in reducing
      HCHO-related cancer risks.

PMID- 28441489
TI  - Comparison of Gasoline Direct-Injection (GDI) and Port Fuel Injection (PFI)
      Vehicle Emissions: Emission Certification Standards, Cold-Start, Secondary
      Organic Aerosol Formation Potential, and Potential Climate Impacts.
AB  - Recent increases in the Corporate Average Fuel Economy standards have led to
      widespread adoption of vehicles equipped with gasoline direct-injection (GDI)
      engines. Changes in engine technologies can alter emissions. To quantify these
      effects, we measured gas- and particle-phase emissions from 82 light-duty
      gasoline vehicles recruited from the California in-use fleet tested on a chassis
      dynamometer using the cold-start unified cycle. The fleet included 15 GDI
      vehicles, including 8 GDIs certified to the most-stringent emissions standard,
      superultra-low-emission vehicles (SULEV). We quantified the effects of engine
      technology, emission certification standards, and cold-start on emissions. For
      vehicles certified to the same emissions standard, there is no statistical
      difference of regulated gas-phase pollutant emissions between PFIs and GDIs.
      However, GDIs had, on average, a factor of 2 higher particulate matter (PM) mass
      emissions than PFIs due to higher elemental carbon (EC) emissions. SULEV
      certified GDIs have a factor of 2 lower PM mass emissions than GDIs certified as
      ultralow-emission vehicles (3.0 +/- 1.1 versus 6.3 +/- 1.1 mg/mi), suggesting
      improvements in engine design and calibration. Comprehensive organic speciation
      revealed no statistically significant differences in the composition of the
      volatile organic compounds emissions between PFI and GDIs, including benzene,
      toluene, ethylbenzene, and xylenes (BTEX). Therefore, the secondary organic
      aerosol and ozone formation potential of the exhaust does not depend on engine
      technology. Cold-start contributes a larger fraction of the total unified cycle
      emissions for vehicles meeting more-stringent emission standards. Organic gas
      emissions were the most sensitive to cold-start compared to the other pollutants
      tested here. There were no statistically significant differences in the effects
      of cold-start on GDIs and PFIs. For our test fleet, the measured 14.5% decrease
      in CO2 emissions from GDIs was much greater than the potential climate forcing
      associated with higher black carbon emissions. Thus, switching from PFI to GDI
      vehicles will likely lead to a reduction in net global warming.

PMID- 28441490
TI  - Asymmetric Synthesis of cis-3,4-Dihydrocoumarins via [4 + 2] Cycloadditions
      Catalyzed by Amidine Derivatives.
AB  - A highly efficient chiral amidine derivative-catalyzed tandem Michael
      addition/lactonization of carboxylic acids and o-quinone methides (o-QMs) has
      been developed that enables the asymmetric synthesis of cis-3,4-dihydrocoumarins
      bearing contiguous tertiary stereogenic centers in high yields with excellent
      stereoselectivities.

PMID- 28441491
TI  - A Naturally Occurring Isoform-Specific Probe for Highly Selective and Sensitive
      Detection of Human Cytochrome P450 3A5.
AB  - Cytochrome P450 (CYP) 3A5 characterized with polymorphic and extensive expression
      in multiple tissues is the most important P450 enzyme among the minor CYP3A
      isoforms. However, a selective and sensitive probe for CYP3A5 remains
      unavailable. In this study, we identified and characterized a naturally occurring
      lignan 12 (schisantherin E) as an isoform-specific probe for selective detection
      of CYP3A5 activity in complex biological samples. With thorough characterization
      including LC-MS and NMR, we found that 12 can be metabolized by CYP3A5 to
      generate a major metabolite 2-O-demethylated 12. Meanwhile, both reaction
      phenotyping and chemical inhibition experiments further revealed that CYP3A5
      selectively catalyzed the 2-O-demethylation of 12. Specifically, the interactions
      between the Phe210 residue of CYP3A5 and methyl benzoate of 12 might play key
      roles in 12-O-demethylation, which was revealed by docking simulation and site
      directed mutagenesis studies. These findings are beneficial for exploring the
      role of CYP3A5 in drug metabolism and pathologic process.

PMID- 28441493
TI  - Systematic Study on Hydrated Arginine: Clear Theoretical Evidence for the
      Canonical-to-Zwitterionic Structure Transition.
AB  - Extensive ab initio investigations have been performed to characterize the stable
      conformers of hydrated arginine (Arg-H2O). Many new low-energy canonical Arg-H2O
      conformers were identified and they are more stable than previous results. The
      large energy differences (more than 5.00 kcal mol-1) between the canonical and
      zwitterionic Arg-H2O isomers calculated by the composite CBS-QB3 method confirmed
      the dominance of the zwitterions. The micro effects of corrections of the zero
      point energy and the basis set superposition error on the stability of hydrated
      isomers were carefully examined for the first time. The infrared (IR) spectra
      were simulated at a recommended temperature and the notable spectral differences
      enable the unambiguous identification of the different hydrated forms. Further
      transition state calculations revealed that the canonical Arg-H2O can be
      transformed to the zwitterions using the amino group as a bridge. Our study thus
      shows valuable insights into the hydration of large flexible molecules and
      provides solid theoretical evidence for the canonical-to-zwitterionic structure
      transition of hydrated arginine.

PMID- 28441492
TI  - Caenorhabditis elegans PRMT-7 and PRMT-9 Are Evolutionarily Conserved Protein
      Arginine Methyltransferases with Distinct Substrate Specificities.
AB  - Caenorhabditis elegans protein arginine methyltransferases PRMT-7 and PRMT-9 are
      two evolutionarily conserved enzymes, with distinct orthologs in plants,
      invertebrates, and vertebrates. Biochemical characterization of these two enzymes
      reveals that they share much in common with their mammalian orthologs. C. elegans
      PRMT-7 produces only monomethylarginine (MMA) and preferentially methylates R-X-R
      motifs in a broad collection of substrates, including human histone peptides and
      RG-rich peptides. In addition, the activity of the PRMT-7 enzyme is dependent on
      temperature, the presence of metal ions, and the reducing agent dithiothreitol.
      C. elegans PRMT-7 has a substrate specificity and a substrate preference
      different from those of mammalian PRMT7, and the available X-ray crystal
      structures of the PRMT7 orthologs show differences in active site architecture.
      C. elegans PRMT-9, on the other hand, produces symmetric dimethylarginine and MMA
      on SFTB-2, the conserved C. elegans ortholog of human RNA splicing factor SF3B2,
      indicating a possible role in the regulation of nematode splicing. In contrast to
      PRMT-7, C. elegans PRMT-9 appears to be biochemically indistinguishable from its
      human ortholog.

PMID- 28441494
TI  - Role of the Reducing Agent in the Electroless Deposition of Copper on
      Functionalized SAMs.
AB  - Metallized organic layer constructs have a wide range of technological
      applications. Electroless deposition is an attractive technique by which to
      deposit metal overlayers because it is inexpensive and can be performed at low
      temperatures, compatible with organic materials. Amine borane reducing agents are
      versatile and are capable of depositing metals, semiconductors, and even
      insulators. We have investigated the role of amine borane reducing agents in the
      electroless deposition of copper on -CH3-, -OH-, and -COOH-terminated SAMs
      adsorbed on gold using time-of-flight secondary ion mass spectrometry, optical
      microscopy, and complementary MP2 calculations. Three reducing agents were
      studied: amine borane, dimethylamine borane, and trimethylamine borane. At pH >9,
      -COOH-terminated SAMs form copper-carboxylate complexes, which serve as
      nucleation sites for subsequent copper deposition. The rate of copper deposition
      is dependent on the strength of the B-N bond of the amine borane reducing agent.
      Similarly, if the terminal group is nonpolar such as a -CH3 functionality, then
      the rate of copper deposition is dependent on the amine borane B-N bond strength.
      However, in contrast to -COOH-terminated SAMs, copper deposition does not begin
      immediately. If the terminal group contains polar bonds, such as the C-OH bond of
      -OH-terminated SAMs, deposition is dominated by the interaction of the reducing
      agent with the terminal group rather than the relative bond strengths of the
      amine borane reducing agents.

PMID- 28441495
TI  - Catalytic Directional Cutting of Hexagonal Boron Nitride: The Roles of Interface
      and Etching Agents.
AB  - Transition-metal (TM) nanoparticle catalyzed cutting has been proven to be an
      efficient approach to carve out straight channels in graphene to produce high
      quality nanoribbons. However, the applicability of such a catalytic approach to
      hexagonal boron nitride (h-BN) is still an open question due to binary element
      compositions. Here, our ab initio study indicates that long and straight channels
      along either the zigzag or the armchair direction of the BN sheet can be carved
      out, driven by the energetically favored TM-zigzag or TM-armchair BN interface,
      regardless of roughness of the TM particle surface. Optimal experimental
      conditions for the catalytic cutting of either BN or BN/graphene hybrid sheet
      across the domain boundary are proposed via the analysis of the competition
      between TM-BN (or TM-graphene) interface and H-terminated BN (or graphene) edge.
      The computation results can serve to guide the experimental design for the
      production of highly uniform BN (or hybrid BN/graphene) nanoribbons with
      atomically smooth edges.

PMID- 28441496
TI  - Room-Temperature Ferromagnetism in Two-Dimensional Fe2Si Nanosheet with Enhanced
      Spin-Polarization Ratio.
AB  - Searching experimental feasible two-dimensional (2D) ferromagnetic crystals with
      large spin-polarization ratio, high Curie temperature and large magnetic
      anisotropic energy is one key to develop next-generation spintronic nanodevices.
      Here, 2D Fe2Si nanosheet, one counterpart of Hapkeite mineral discovered in
      meteorite with novel magnetism is proposed on the basis of first-principles
      calculations. The 2D Fe2Si crystal has a slightly buckled triangular lattice with
      planar hexacoordinated Si and Fe atoms. The spin-polarized calculations with
      hybrid HSE06 function method indicate that 2D Fe2Si is a ferromagnetic half metal
      at its ground state with 100% spin-polarization ratio at Fermi energy level. The
      phonon spectrum calculation and ab initio molecular dynamic simulation shows that
      2D Fe2Si crystal has a high thermodynamic stability and its 2D lattice can be
      retained at the temperature up to 1200 K. Monte Carlo simulations based on the
      Ising model predict a Curie temperature over 780 K in 2D Fe2Si crystal, which can
      be further tuned by applying a biaxial strain. Moreover, 2D structure and strong
      in-plane Fe-Fe interaction endow Fe2Si nanosheet sizable magnetocrystalline
      anisotropy energy with the magnitude of at least two orders larger than those of
      Fe, Co and Ni bulks. These novel magnetic properties render the 2D Fe2Si crystal
      a very promising material for developing practical spintronic nanodevices.

PMID- 28441497
TI  - Development of a Biorelevant, Material-Sparing Membrane Flux Test for Rapid
      Screening of Bioavailability-Enhancing Drug Product Formulations.
AB  - Bioavailability-enhancing formulations are often used to overcome challenges of
      poor gastrointestinal solubility for drug substances developed for oral
      administration. Conventional in vitro dissolution tests often do not properly
      compare such formulations due to the many different drug species that may exist
      in solution. To overcome these limitations, we have designed a practical in vitro
      membrane flux test, that requires minimal active pharmaceutical ingredient (API)
      and is capable of rapidly screening many drug product intermediates. This test
      can be used to quickly compare performance of bioavailability-enhancing
      formulations with fundamental knowledge of the rate-limiting step(s) to membrane
      flux. Using this system, we demonstrate that the flux of amorphous itraconazole
      (logD = 5.7) is limited by aqueous boundary layer (ABL) diffusion and can be
      increased by adding drug-solubilizing micelles or drug-rich colloids. Conversely,
      the flux of crystalline ketoconazole at pH 5 (logD = 2.2) is membrane-limited,
      and adding solubilizing micelles does not increase flux. Under certain
      circumstances, the flux of ketoconazole may also be limited by dissolution rate.
      These cases highlight how a well-designed in vitro assay can provide critical
      insight for oral formulation development. Knowing whether flux is limited by
      membrane diffusion, ABL diffusion, or dissolution rate can help drive formulation
      development decisions. It may also be useful in predicting in vivo performance,
      dose linearity, food effects, and regional-dependent flux along the length of the
      gastrointestinal tract.

PMID- 28441499
TI  - Low-Loss Plasmonic Dielectric Nanoresonators.
AB  - Material losses in metals are a central bottleneck in plasmonics for many
      applications. Here we propose and theoretically demonstrate that metal losses can
      be successfully mitigated with dielectric particles on metallic films, giving
      rise to hybrid dielectric-metal resonances. In the far field, they yield strong
      and efficient scattering, beyond even the theoretical limits of all-metal and all
      dielectric structures. In the near field, they offer high Purcell factor (>5000),
      high quantum efficiency (>90%), and highly directional emission at visible and
      infrared wavelengths. Their quality factors can be readily tailored from
      plasmonic-like (~10) to dielectric-like (~103), with wide control over the
      individual resonant coupling to photon, plasmon, and dissipative channels.
      Compared with conventional plasmonic nanostructures, such resonances show
      robustness against detrimental nonlocal effects and provide higher field
      enhancement at extreme nanoscopic sizes and spacings. These hybrid resonances
      equip plasmonics with high efficiency, which has been the predominant goal since
      the field's inception.

PMID- 28441498
TI  - Thin-Wall GaN/InAlN Multiple Quantum Well Tubes.
AB  - Thin-wall tubes composed of nitride semiconductors (III-N compounds) based on
      GaN/InAlN multiple quantum wells (MQWs) are fabricated by metal-organic vapor
      phase epitaxy in a simple and full III-N approach. The synthesis of such MQW
      tubes is based on the growth of N-polar c-axis vertical GaN wires surrounded by a
      core-shell MQW heterostructure followed by in situ selective etching using
      controlled H2/NH3 annealing at 1010  degrees C to remove the inner GaN wire part.
      After this process, well-defined MQW-based tubes having nonpolar m-plane
      orientation exhibit UV light near 330 nm up to room temperature, consistent with
      the emission of GaN/InAlN MQWs. Partially etched tubes reveal a quantum-dotlike
      signature originating from nanosized GaN residuals present inside the tubes. The
      possibility to fabricate in a simple way thin-wall III-N tubes composed of an
      embedded MQW-based active region offering controllable optical emission
      properties constitutes an important step forward to develop new nitride devices
      such as emitters, detectors or sensors based on tubelike nanostructures.

PMID- 28441500
TI  - Thermoplasmonic Semitransparent Nanohole Electrodes.
AB  - Nonradiative decay of plasmons in metallic nanostructures offers unique means for
      light-to-heat conversion at the nanoscale. Typical thermoplasmonic systems
      utilize discrete particles, while metal nanohole arrays were instead considered
      suitable as heat sinks to reduce heating effects. By contrast, we show for the
      first time that under uniform broadband illumination (e.g., the sun) ultrathin
      plasmonic nanohole arrays can be highly competitive plasmonic heaters and provide
      significantly higher temperatures than analogous nanodisk arrays. Our plasmonic
      nanohole arrays also heat significantly more than nonstructured metal films,
      while simultaneously providing superior light transmission. Besides being
      efficient light-driven heat sources, these thin perforated gold films can
      simultaneously be used as electrodes. We used this feature to develop "plasmonic
      thermistors" for electrical monitoring of plasmon-induced temperature changes.
      The nanohole arrays provided temperature changes up to 7.5 K by simulated
      sunlight, which is very high compared to previously reported plasmonic systems
      under similar conditions (solar illumination and ambient conditions). Both
      temperatures and heating profiles quantitatively agree with combined optical and
      thermal simulations. Finally, we demonstrate the use of a thermoplasmonic
      nanohole electrode to power the first hybrid plasmonic ionic thermoelectric
      device, resulting in strong solar-induced heat gradients and corresponding
      thermoelectric voltages.

PMID- 28441501
TI  - Hooked on Cryogels: A Carbamate Linker Based Depot for Slow Drug Release.
AB  - Poly(ethylene glycol) (PEG) based bulk hydrogels and cryogels containing
      activated carbonate groups as amine reactive handles to facilitate drug
      conjugations through carbamate linkages were fabricated and evaluated as slow
      releasing drug reservoirs. As an initial approach, photopolymerization of N
      hydroxysuccinimide (NHS)-activated carbonate functional group containing monomer
      and PEG-methacrylate in the presence of a cross-linker was utilized to obtain
      bulk hydrogels with high gel conversions. The resultant hydrogels possessed
      moderate water uptake (170-340%) which was dependent on the monomer ratios. These
      hydrogels were functionalized with an anticancer drug, namely, doxorubicin.
      Surprisingly, while negligible drug release was observed from the bulk hydrogels
      under normal pH, only about 6% drug release was observed under acidic condition.
      Limited swelling of these hydrogels as well as lack of porous structure as
      deduced from scanning electron microscopy analysis might explain the poor drug
      release. To enhance the drug releasing capacity of these hydrogels that might
      stem from the increased porosity, reactive carbonate group bearing cryogels were
      synthesized. Compared to the bulk hydrogels, cryogels were highly porous in
      structure and also possessed much higher swelling capacity (1150-1500%). As a
      result of these distinctions, a 7-fold enhancement in drug release was observed
      for the cryogel system compared to the relating hydrogel. In vitro studies
      demonstrated that the anticancer drug doxorubicin conjugated through carbamate
      linkers to the cryogels was released and proved effective against MDA-MB-231
      human breast cancer cells. Overall, a novel class of slow releasing nontoxic
      hydrogel and cryogel scaffolds with potential applications as anticancer drug
      reservoirs was realized.

PMID- 28441503
TI  - Robust, Uniform, and Highly Emissive Quantum Dot-Polymer Films and Patterns Using
      Thiol-Ene Chemistry.
AB  - This work demonstrates a facile and versatile method for generating low
      scattering cross-linked quantum dot (QD)-polymer composite films and patterned
      highly emissive structures with ultrahigh QD loading, minimal phase separation,
      and tunable mechanical properties. Uniform QD-polymer films are fabricated using
      thiol-ene chemistry, in which cross-linked polymer networks are rapidly produced
      in ambient conditions via fast UV polymerization in bulk to suppress QD
      aggregation. UV-controlled thiol-ene chemistry limits phase separation through
      producing highly QD loaded cross-linked composites with loadings above majority
      of those reported in the literature (<1%) and approaching 30%. As the QD loading
      is increased, the thiol and ene conversion decreases, resulting in nanocomposites
      with widely variable and tailorable mechanical properties as a function of UV
      irradiation time with an elastic modulus decreasing to 1 GPa being characteristic
      of reinforced elastomeric materials, in contrast to usually observed stiff and
      brittle materials under these loading conditions. Furthermore, we demonstrate
      that the thiol-ene chemistry is compatible with soft-imprint lithography, making
      it possible to pattern highly loaded QD films while preserving the optical
      properties essential for high gain and low optical loss devices. The versatility
      of thiol-ene chemistry to produce high-dense QD-polymer films potentially makes
      it an important technique for polymer-based elastomeric optical metamaterials,
      where efficient light propagation is critical, like peculiar waveguides, sensors,
      and optical gain films.

PMID- 28441502
TI  - Differential Coupling of Binding, ATP Hydrolysis, and Transport of Fluorescent
      Probes with P-Glycoprotein in Lipid Nanodiscs.
AB  - The ATP binding cassette transporter P-glycoprotein (ABCB1 or P-gp) plays a major
      role in cellular resistance to drugs and drug interactions. Experimental studies
      support a mechanism with nucleotide-dependent fluctuation between inward-facing
      and outward-facing conformations, which are coupled to nucleotide hydrolysis.
      However, detailed insight into drug-dependent modulation of these conformational
      ensembles is lacking. Different drugs likely occupy partially overlapping but
      distinct sites and are therefore variably coupled to nucleotide binding and
      hydrolysis. Many fluorescent drug analogues are used in cell-based transport
      models; however, their specific interactions with P-gp have not been studied, and
      this limits interpretation of transport assays in terms of molecular models. Here
      we monitor binding of the fluorescent probe substrates BODIPY-verapamil, BODIPY
      vinblastine, and Flutax-2 at low occupancy to murine P-gp in lipid nanodiscs via
      fluorescence correlation spectroscopy, in variable nucleotide-bound states.
      Changes in affinity for the different nucleotide-dependent conformations are
      probe-dependent. For BODIPY-verapamil and BODIPY-vinblastine, there are 2-10-fold
      increases in KD in the nucleotide-bound or vanadate-trapped state, compared to
      that in the nucleotide-free state. In contrast, the affinity of Flutax-2 is
      unaffected by nucleotide or vanadate trapping. In further contrast to BODIPY
      verapamil and BODIPY-vinblastine, Flutax-2 does not cause stimulation of ATP
      hydrolysis despite the fact that it is transported in vesicle-based transport
      assays. Whereas the established substrates verapamil, paclitaxel, and vinblastine
      displace BODIPY-verapamil or BODIPY-vinblastine from their high-affinity sites,
      the transport substrate Flutax-2 is not displaced by any of these substrates. The
      results demonstrate a unique binding site for Flutax-2 that allows for transport
      without stimulation of ATP hydrolysis.

PMID- 28441504
TI  - Paradoxical Long-Timespan Opening of the Hole in Self-Supported Water Films of
      Nanometer Thickness.
AB  - The opening of holes in self-supported thin (nanoscaled) water films has been
      investigated in situ with the environmental scanning electron microscope. The
      opening of a hole occurs within a two-stage process. In the first stage, the rim
      surrounding a hole is formed, resembling the process that is observed under the
      puncturing of soap bubbles. In the second stage, the exponential growth of the
      hole is observed, with a characteristic time of a dozen seconds. We explain the
      exponential kinetics of hole growth by the balance between inertia (gravity) and
      viscous dissipation. The kinetics of opening a microscaled hole is governed by
      the processes taking place in the nanothick bulk of the self-supported liquid
      film. Nanoparticles provide markers for the visualization of the processes
      occurring in self-supported thin nanoscale liquid films.

PMID- 28441505
TI  - Error Detection-Based Model to Assess Educational Outcomes in Crisis Resource
      Management Training: A Pilot Study.
AB  - Otolaryngology-head and neck surgery (OTL-HNS) residents face a variety of
      difficult, high-stress situations, which may occur early in their training. Since
      these events occur infrequently, simulation-based learning has become an
      important part of residents' training and is already well established in fields
      such as anesthesia and emergency medicine. In the domain of OTL-HNS, it is
      gradually gaining in popularity. Crisis Resource Management (CRM), a program
      adapted from the aviation industry, aims to improve outcomes of crisis situations
      by attempting to mitigate human errors. Some examples of CRM principles include
      cultivating situational awareness; promoting proper use of available resources;
      and improving rapid decision making, particularly in high-acuity, low-frequency
      clinical situations. Our pilot project sought to integrate CRM principles into an
      airway simulation course for OTL-HNS residents, but most important, it evaluated
      whether learning objectives were met, through use of a novel error identification
      model.

PMID- 28441507
TI  - New Metrics for Economic Evaluation in the Presence of Heterogeneity: Focusing on
      Evaluating Policy Alternatives Rather than Treatment Alternatives.
AB  - BACKGROUND: Cost-effectiveness analysis (CEA) methods fail to acknowledge that
      where cost-effectiveness differs across subgroups, there may be differential
      adoption of technology. Also, current CEA methods are not amenable to
      incorporating the impact of policy alternatives that potentially influence the
      adoption behavior. Unless CEA methods are extended to allow for a comparison of
      policies rather than simply treatments, their usefulness to decision makers may
      be limited. METHODS: We conceptualize new metrics, which estimate the realized
      value of technology from policy alternatives, through introducing subgroup
      specific adoption parameters into existing metrics, incremental cost
      effectiveness ratios (ICERs) and Incremental Net Monetary Benefits (NMBs). We
      also provide the Loss with respect to Efficient Diffusion (LED) metrics, which
      link with existing value of information metrics but take a policy evaluation
      perspective. We illustrate these metrics using policies on treatment with
      combination therapy with a statin plus a fibrate v. statin monotherapy for
      patients with diabetes and mixed dyslipidemia. RESULTS: Under the traditional
      approach, the population-level ICER of combination v. monotherapy was
      $46,000/QALY. However, after accounting for differential rates of adoption of the
      combination therapy (7.2% among males and 4.3% among females), the modified ICER
      was $41,733/QALY, due to the higher rate of adoption in the more cost-effective
      subgroup (male). The LED metrics showed that an education program to increase the
      uptake of combination therapy among males would provide the largest economic
      returns due to the significant underutilization of the combination therapy among
      males under the current policy. CONCLUSION: This framework may have the potential
      to improve the decision-making process by producing metrics that are better
      aligned with the specific policy decisions under consideration for a specific
      technology.

PMID- 28441508
TI  - CyberKnife for Treatment of Vestibular Schwannoma: A Meta-analysis.
AB  - Objectives (1) Perform a meta-analysis of the available data on the outcomes of
      CyberKnife radiosurgery for treatment of vestibular schwannomas (VSs) in the
      published English-language literature and (2) evaluate the collective outcomes of
      CyberKnife treatment with respect to tumor control and hearing preservation. Data
      Sources A thorough literature search of published English-language articles was
      performed in the PubMed, Ovid, and Cochrane databases. Review Methods A database
      search was conducted with the keywords "CyberKnife" and "vestibular schwannoma"
      or "acoustic neuroma." A total of 25 papers were found and reviewed. Data were
      extracted for patient demographics, number of patients with neurofibromatosis
      type 2, pretreatment hearing status, tumor size, margin dose, and follow-up
      duration. The primary outcome variables evaluated were tumor control and hearing
      preservation. Results After careful review of the published articles, 11 papers
      reported data on outcomes of CyberKnife treatment for VS and were included in the
      analysis, comprising 800 patients studied during 1998 to 2012. The reported mean
      tumor volume ranged from 0.02 to 19.8 cm3, and the follow-up duration ranged from
      6 to 120 months. Margin dose varied from 14 to 25 Gy. The collective mean tumor
      control rate was 96.3% (95% CI: 94.0%-98.5%). The collective hearing preservation
      rate was 79.1% (95% CI: 71.0%-87.3%) in 427 patients with measurable hearing.
      Conclusion Clinical data on outcomes of CyberKnife radiosurgery for treatment of
      VSs are sparse and primarily limited to single-institution analyses, with
      considerable variation in tumor volume and follow-up time. This meta-analysis not
      only provides an in-depth analysis of available data in the literature but also
      reviews reported outcomes and complications.

PMID- 28441509
TI  - Patient Safety and Quality Improvement in Otolaryngology Education: A Systematic
      Review.
AB  - Objective The breadth and depth of patient safety/quality improvement (PS/QI)
      research dedicated to otolaryngology-head and neck surgery (OHNS) education
      remains unknown. This systematic review aims to define this scope and to identify
      knowledge gaps as well as potential areas of future study to improved PS/QI
      education and training in OHNS. Data Sources A computerized Ovid/Medline database
      search was conducted (January 1, 1965, to May 15, 2015). Similar computerized
      searches were conducted using Cochrane Database, PubMed, and Google Scholar.
      Review Methods The study protocol was developed a priori using the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles were
      classified by year, subspecialty, Institute of Medicine (IOM) Crossing the Chasm
      categories, and World Health Organization (WHO) subclass. Results Computerized
      searches yielded 8743 eligible articles, 267 (3.4%) of which met otolaryngology
      PS/QI inclusion criteria; 51 (19%) were dedicated to resident/fellow education
      and training. Simulation studies (39%) and performance/competency evaluation
      (23.5%) were the most common focus. Most projects involved general otolaryngology
      (47%), rhinology (18%), and otology (16%). Classification by the IOM included
      effective care (45%), safety/effective care (41%), and effective and efficient
      care (7.8%). Most research fell into the WHO category of "identifying solutions"
      (61%). Conclusion Nineteen percent of OHNS PS/QI articles are dedicated to
      education, the majority of which are simulation and focus on effective care.
      Knowledges gaps for future research include facial plastics PS/QI and the WHO
      category of "studies translating evidence into safer care."

PMID- 28441511
TI  - Do Patients With Borderline Dysplasia Have Inferior Outcomes After Hip
      Arthroscopic Surgery for Femoroacetabular Impingement Compared With Patients With
      Normal Acetabular Coverage?
AB  - BACKGROUND: The literature contains conflicting reports regarding whether
      outcomes of hip arthroscopic surgery for patients with borderline dysplasia are
      inferior to outcomes in patients with normal acetabular coverage. PURPOSE: To
      assess differences in the outcomes of hip arthroscopic surgery for
      femoroacetabular impingement (FAI) in groups of patients with borderline
      dysplasia and normal coverage. STUDY DESIGN: Cohort study; Level of evidence, 3.
      METHODS: A registry of consecutive patients who had undergone primary hip
      arthroscopic surgery with capsular plication for FAI between January 2012 and
      January 2014 were divided based on the preoperative lateral center-edge angle
      (LCEA) into 2 distinct groups: (1) borderline dysplasia (LCEA 18 degrees -25
      degrees ) and (2) normal acetabular coverage (LCEA 25.1 degrees -40 degrees ).
      There were 36 patients in the borderline dysplastic group and 312 patients in the
      normal coverage group. The primary outcome measure was the Hip Outcome Score
      Activities of Daily Living (HOS-ADL) at a minimum of 2 years postoperatively.
      Secondary outcome measures included the HOS-Sports and modified Harris Hip Score
      (mHHS). RESULTS: The mean preoperative LCEA differed significantly between groups
      (23.4 degrees  +/- 1.5 degrees  for borderline dysplastic, 32.5 degrees  +/- 3.8
      degrees  for normal coverage; P < .001). The borderline dysplastic group had a
      higher percentage of female patients than the normal coverage group (27/36 [75%]
      vs 177/312 [57%], respectively; P = .048). There were no differences in other
      preoperative demographics and radiographic parameters. At a minimum 2 years after
      hip arthroscopic surgery (mean follow-up, 2.6 +/- 0.6 years), both groups
      demonstrated significant improvements in all patient-reported outcome scores ( P
      < .001 in all cases). There were no significant differences between the
      borderline dysplastic and normal coverage groups in final outcome scores, score
      improvements, or percentage of patients experiencing clinically significant
      improvements. One patient in the borderline dysplastic group (3%) underwent
      revision hip arthroscopic surgery, and none underwent total hip arthroplasty
      during the follow-up period. There were no differences between the borderline
      dysplastic and normal coverage groups with regard to subsequent surgery. Female
      patients in the borderline dysplastic group had greater improvements in the mean
      HOS-ADL (25.9 +/- 16.3 vs 10.8 +/- 18.5, respectively; P = .05) and mHHS (27.9 +/
      12.9 vs 8.1 +/- 19.0, respectively; P = .005) compared with male patients in the
      borderline dysplastic group, but male and female patients did not differ in
      outcomes for the normal coverage group. CONCLUSION: Patients who underwent hip
      arthroscopic surgery for FAI with capsular plication experienced significant
      clinical improvements with low rates of subsequent surgery, regardless of whether
      their acetabulum had borderline dysplasia or normal coverage.

PMID- 28441512
TI  - A Historical Perspective on the Transport of Premature Infants.
AB  - A premature newborn was first transported via helicopter from place of birth to a
      specialty nursery 50 years ago. Since that time, the care of high-risk and
      premature newborns has evolved, but specialized services are not always available
      at the birth site. As a result, the demand for newborn transfer continues to
      grow. Today, neonates are transported to tertiary centers via ground ambulances,
      helicopters, and airplanes by highly trained personnel using sophisticated
      incubators and equipment.

PMID- 28441513
TI  - Antibody persistence following meningococcal C conjugate vaccination in children
      and adolescents infected with human immunodeficiency virus.
AB  - OBJECTIVE: HIV-infected individuals (HIVI) are threatened by meningococcal
      infection and presented lower response to vaccines. Data are scarce on long-term
      persistence of human serum bactericidal antibody (hSBA) after a meningococcal C
      conjugate (MCC) vaccine in HIVI youth; the authors aimed to describe this
      persistence in HIVI. METHODS: HIVI and HIV uninfected individuals (HIVU), aged 2
      18 years, CD4 >15% were recruited. Seroprotection (hSBA >=1:4) at baseline and at
      12-18 months after immunization was evaluated and the association of the
      different factors with the long-term persistence was calculated using logistic
      regression. RESULTS: A total of 145 HIVI, 50 HIVU were recruited and immunized,
      and their median age was 11 years (median age in HIVI group was 12 years, and 10
      years in HIVU group, p-value=0.02). 85 HIVI (44%) had undetectable viral load
      (UVL). Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12-18 months
      after immunization (p=0.14). Baseline immunity (odds ratio [OR]=70.70, 95% CI:
      65.2-766.6); UVL at entry (OR: 2.87, 95% CI: 0.96-8.62) and lower family income
      (OR: 0.09, 95% CI: 0.01-0.69) were associated with seroprotection among HIVI.
      CONCLUSION: Seroprotection at 12-18 months after single dose of MCC was low for
      both groups, and higher among individuals who presented baseline immunity. Among
      HIVI, vaccine should be administered after UVL is achieved.

PMID- 28441514
TI  - Sleep and electronic media exposure in adolescents: the rule of diminishing
      returns.

PMID- 28441515
TI  - Among Active Surveillance Candidates does Obesity Influence Tumor Aggressiveness
      and/or Location?

PMID- 28441516
TI  - Epoxynemanione A, nemanifuranones A-F, and nemanilactones A-C, from Nemania
      serpens, an endophytic fungus isolated from Riesling grapevines.
AB  - Ten polyketide specialized metabolites, epoxynemanione A, nemanifuranones A-F,
      and nemanilactones A-C, were isolated from the culture filtrate of Nemania
      serpens (Pers.) Grey (1821), an endophytic fungus from a Riesling grapevine
      (Vitis vinifera) found in Canada's Niagara region. Additionally, four known
      metabolites 2-(hydroxymethyl)-3-methoxy-benzoic acid, phyllostine, 5
      methylmellein and a nordammarane triterpenoid were isolated. A related known
      metabolite 2,3-dihydro-2-hydroxy-2,4-dimethyl-5-trans-propenylfuran-3-one has
      also been included for structural and biological comparison to the
      nemanifuranones. The latter was isolated from the culture filtrates of Mollisia
      nigrescens, an endophytic fungus from the leaves and stems of lowbush blueberry
      (Vaccinium angustifolium) found in the Acadian forest of Nova Scotia, Canada.
      Their structures were elucidated based on 1D and 2D NMR, HRESIMS measurements, X
      ray crystallographic analysis of nemanifuranone A, the nordammarane triterpenoid
      and 2,3-dihydro-2-hydroxy-2,4-dimethyl-5-trans-propenylfuran-3-one compounds, and
      comparison of NOE and vicinal 1H-1H coupling constants to literature data for
      relative stereochemical assignments. Nemanifuranone A possesses a rare C2
      hemiacetal and was active against both Gram-negative and Gram-positive bacteria.

PMID- 28441517
TI  - Mild Cognitive Impairment and driving: Does in-vehicle distraction affect driving
      performance?
AB  - OBJECTIVES: In-vehicle distraction is considered to be an important cause of road
      accidents. Drivers with Mild Cognitive Impairment (MCI), because of their
      attenuated cognitive resources, may be vulnerable to the effects of distraction;
      however, previous relevant research is lacking. The main objective of the current
      study was to explore the effect of in-vehicle distraction on the driving
      performance of MCI patients, by assessing their reaction time at unexpected
      incidents and accident probability. METHODS: Thirteen patients with MCI (age:
      64.5+/-7.2) and 12 cognitively intact individuals (age: 60.0+/-7.7), all active
      drivers were introduced in the study. The driving simulator experiment included
      three distraction conditions: (a) undistracted driving, (b) conversing with
      passenger and (c) conversing through a hand-held mobile phone. RESULTS: The mixed
      ANOVA models revealed a greater effect of distraction on MCI patients.
      Specifically, the use of mobile phone induced a more pronounced impact on
      reaction time and accident probability in the group of patients, as compared to
      healthy controls. On the other hand, in the driving condition "conversing with
      passenger" the interaction effects regarding reaction time and accident
      probability were not significant. Notably, the aforementioned findings concerning
      the MCI patients in the case of the mobile phone were observed despite the effort
      of the drivers to apply a compensatory strategy by reducing significantly their
      speed in this driving condition. CONCLUSION: Overall, the current findings
      indicate, for the first time, that a common driving practice, such as the use of
      mobile phone, may have a detrimental impact on the driving performance of
      individuals with MCI.

PMID- 28441518
TI  - Learning to allocate limited time to decisions with different expected outcomes.
AB  - The goal of this article is to investigate how human participants allocate their
      limited time to decisions with different properties. We report the results of two
      behavioral experiments. In each trial of the experiments, the participant must
      accumulate noisy information to make a decision. The participants received
      positive and negative rewards for their correct and incorrect decisions,
      respectively. The stimulus was designed such that decisions based on more
      accumulated information were more accurate but took longer. Therefore, the total
      outcome that a participant could achieve during the limited experiments' time
      depended on her "decision threshold", the amount of information she needed to
      make a decision. In the first experiment, two types of trials were intermixed
      randomly: hard and easy. Crucially, the hard trials were associated with smaller
      positive and negative rewards than the easy trials. A cue presented at the
      beginning of each trial would indicate the type of the upcoming trial. The
      optimal strategy was to adopt a small decision threshold for hard trials. The
      results showed that several of the participants did not learn this simple
      strategy. We then investigated how the participants adjusted their decision
      threshold based on the feedback they received in each trial. To this end, we
      developed and compared 10 computational models for adjusting the decision
      threshold. The models differ in their assumptions on the shape of the decision
      thresholds and the way the feedback is used to adjust the decision thresholds.
      The results of Bayesian model comparison showed that a model with time-varying
      thresholds whose parameters are updated by a reinforcement learning algorithm is
      the most likely model. In the second experiment, the cues were not presented. We
      showed that the optimal strategy is to use a single time-decreasing decision
      threshold for all trials. The results of the computational modeling showed that
      the participants did not use this optimal strategy. Instead, they attempted to
      detect the difficulty of the trial first and then set their decision threshold
      accordingly.

PMID- 28441519
TI  - Grounding principles for inferring agency: Two cultural perspectives.
AB  - The present research investigates cultural variation in grounding principles for
      inferring agency in order to address an important theoretical debate: does
      cultural diversity in agency concepts reflect an animistic overextension of
      (universal) folkpsychology, as many have argued, or an alternative theory of
      folkcommunication based on relational principles? In two experiments, mind
      perception measures were adapted to assess beliefs concerning the agency of non
      animal kinds (plants, abiotic kinds, complex artifacts) among Indigenous Ngobe
      adults in Panama and US college students. Agency attributions varied
      systematically, with Ngobe ascribing greater agency to non-animal natural kinds
      and US college participants ascribing greater agency to complex artifacts.
      Analysis of explanations revealed divergent interpretations of agency as a
      prototypically human capacity requiring consciousness (US), versus a relational
      capacity expressed in directed interactions (Ngobe). Converging measures further
      illuminated the inferential principles underlying these agency attributions. (1)
      An experimental relational framing of agency probes facilitated Ngobe but not US
      agency attributions. (2) Further analysis showed that three key dimensions of
      agency attribution (experience, cognition, animacy) are organized differently
      across cultures. (3) A Bayesian approach to cultural consensus modeling confirmed
      the presence of two distinct consensus models rather than variations on a single
      (universal) model. Together, these results indicate that conceptual frameworks
      for agency differ across US college and Ngobe communities. We conclude that Ngobe
      concepts of agency derive from a distinct theory of folkcommunication based on an
      ecocentric prototype rather than overextensions of an anthropocentric
      folkpsychology. These observations suggest that folkpsychology and mind
      perception represent culture specific frameworks for agency, with significant
      implications for domain-specificity theory and our understanding of cognitive
      diversity.

PMID- 28441520
TI  - Age, gender and deterrability: Are younger male drivers more likely to discount
      the future?
AB  - Utilizing the Classical Deterrence theory and Stafford and Warr's (1993)
      reconceptualized model of deterrence, the current study examined whether age,
      gender, and discounting the future tendencies influence perceptions of being
      apprehended for speeding offences. Licensed motorists (N=700; 57% female) in
      Queensland (Australia) were recruited to complete a self-report questionnaire
      that measured perceptual deterrence, speeding related behaviors and discounting
      the future tendencies. Data were analyzed utilizing descriptive, bivariate and
      multivariate regressions. Significant (albeit weak) positive correlations were
      found between age and perceptions of apprehension certainty. Males were
      significantly more likely to report higher incidences of speeding (including
      while avoiding detection) compared to females. In contrast, females were more
      likely to perceive high levels of apprehension certainty and consider impending
      penalties to be more severe. At a multivariate level, discounting the future
      tendencies (in addition to being male, reporting lower levels of perceptual
      severity and swiftness, and more instances of punishment avoidance) were
      predictive of lower perceptual certainty levels. This study is one of the first
      to reveal that being male and having a tendency to discount the consequences of
      the future may directly influence drivers' perceptual deterrence levels.

PMID- 28441521
TI  - Lost in distractors: Reduced Autobiographical Memory Specificity and dispersed
      activation spreading over distractors in working memory.
AB  - Studies on autobiographical memory retrieval highlight the prominence of rapid
      and direct access to a specific event memory. Because it has been believed that
      autobiographical memory retrieval mostly relies on an effortful generative
      process, there is little empirical evidence on the early stage of information
      processing that contributes to autobiographical memory specificity (AMS).
      Therefore, we investigated the associations between AMS and automatic activation
      of information stimulated by rapid presentation of emotional words. Study 1
      involved a visual search task to assess activation of various distractors in
      working memory. Participants with reduced AMS showed a tendency to activate
      distractors that were not semantically associated with preceding cues. In Study
      2, we manipulated the levels of AMS by using a computerized version of Memory
      Specificity Training (c-MeST) to observe the changes in the activation of
      distractors. Results showed that increases in AMS were associated with decreases
      in activation of cue-unassociated distractors. These findings suggest that
      reduced AMS can be characterized by dispersed activation spreading over
      semantically unassociated distractors in automatic information selection of
      working memory. Because we also found an association between depressive symptoms
      and AMS, the role of automatic information processing in the relation between
      reduced AMS and depression is discussed.

PMID- 28441522
TI  - Feeling safe but appearing anxious: Differential effects of alcohol on anxiety
      and social performance in individuals with social anxiety disorder.
AB  - Social anxiety disorder (SAD) and alcohol use disorders (AUD) co-occur frequently
      and there is preliminary evidence that alcohol might reduce social anxiety. It
      is, however, unclear which mechanisms contribute to the anxiety reducing effect,
      particularly regarding key aspects of social anxiety such as deficits in social
      performance. We compared self-rated and physiological measures of anxiety as well
      as self- and observer-rated social performance in a sample of 62 individuals with
      SAD and 60 nonanxious control participants during a speech task after receiving
      either alcohol, an alcohol-free placebo drink or orange juice. SAD patients
      reported more anxiety during the speech task than did control participants.
      Furthermore, SAD patients underestimated their performance in comparison to
      observer ratings. Alcohol reduced self-report anxiety only in SAD patients, while
      observers rated all participants as less competent when intoxicated. Although
      individuals with SAD experience a reduction in anxiety when drinking alcohol,
      simultaneous decreases in social performance might contribute to negative
      reactions from others and consequently increase the risk of further alcohol use
      to cope with these negative reactions.

PMID- 28441523
TI  - Carbohydrates and gibberellins relationship in potato tuberization.
AB  - Potato represents the third most important crop worldwide and therefore to
      understand regulations of tuber onset is crucial from both theoretical and
      practical points of view. Photosynthesis and related carbohydrate status along
      with phytohormone balance belong to the essential factors in regulation of plant
      development including storage organ formation. In our work we used potato
      (Solanum tuberosum) cv. Lada and its spontaneously tuberizing mutant (ST plants)
      grown in vitro under low carbohydrate availability (non-inductive conditions).
      Small plant phenotype and readiness to tuberization of ST plants was, however,
      not accompanied by lower gibberellins levels, as determined by UHPLC-MS/MS.
      Therefore, we focused on the other inducing factor, carbohydrate status. Using
      HPLC, we followed changes in carbohydrate distribution under mixotrophic (2.5%
      sucrose in medium) and photoautotrophic conditions (no sucrose addition and
      higher gas and light availability) and observed changes in soluble carbohydrate
      allocation and starch deposition, favouring basal stem part in mutants. In
      addition, the determination of tuber-inducing marker gene expressions revealed
      increased levels of StSP6A in ST leaves. Collectively these data point towards
      the possibility of two parallel cross-talking pathways (carbohydrate - and
      gibberellin- dependent ones) with the power of both to outcompete the other one
      when its signal is for some reason extraordinary strong.

PMID- 28441524
TI  - Sequential Rosettes Drive C. elegans Ventral Nerve Cord Assembly.
AB  - Planar cell polarity (PCP) signaling orients developmental events in vertebrates
      and invertebrates, including convergent extension (CE). In this issue of
      Development Cell, Shah and Tanner et al. (2017) report that ROBO/SAX-3 signaling
      acts in parallel with PCP signaling to drive the CE required for ventral nerve
      cord assembly in C. elegans.

PMID- 28441525
TI  - MYRFs on the Move to Rewire Circuits.
AB  - Synaptic plasticity occurs in response to intrinsic and extrinsic cues and is a
      key step in the formation of mature neuronal circuits. In this issue of
      Developmental Cell, Meng et al. (2017) find that two conserved Myrf transcription
      factors coexist in the same complex to promote developmental circuit remodeling.

PMID- 28441526
TI  - It's T Time for Normal Blood Vessels.
AB  - In a new report in Nature, Tian and colleagues (2017) describe that T cell
      activation in tumors induces blood vessel normalization. Because abnormal
      vasculature in tumors is known to reduce chemotherapy effectiveness and T
      lymphocyte infiltration and to increase metastasis, this suggests an exciting
      novel angle for checkpoint immunotherapy.

PMID- 28441527
TI  - Proteostasis or Aging: Let the CHIPs Fall Where They May.
AB  - The conserved E3 ubiquitin ligase CHIP/CHN-1 contributes to proteostasis by
      ubiquitylating HSP70 and HSP90-interacting proteins. In a recent issue of
      Cell,Tawo et al. (2017) show that CHIP/CHN-1 also directly ubiquitylates the
      insulin receptor INSR/DAF-2 to regulate its turnover. These findings suggest an
      unexpected interpretation of the effects of altered proteostasis on survival.

PMID- 28441528
TI  - Phosphorylation of NEUROG3 Links Endocrine Differentiation to the Cell Cycle in
      Pancreatic Progenitors.
AB  - During pancreatic development, proliferating pancreatic progenitors activate the
      proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle,
      and differentiate into islet cells. The mechanisms that direct robust NEUROG3
      expression within a subset of progenitor cells control the size of the endocrine
      population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus
      on serine 183, which catalyzes its hyperphosphorylation and proteosomal
      degradation. During progression through the progenitor cell cycle, NEUROG3
      phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at
      G1/S cell-cycle checkpoint. Using models of mouse and human pancreas development,
      we show that lengthening of the G1 phase of the pancreatic progenitor cell cycle
      is essential for proper induction of NEUROG3 and initiation of endocrine cell
      differentiation. In sum, these studies demonstrate that progenitor cell-cycle G1
      lengthening, through its actions on stabilization of NEUROG3, is an essential
      variable in normal endocrine cell genesis.

PMID- 28441530
TI  - Aubergine Controls Germline Stem Cell Self-Renewal and Progeny Differentiation
      via Distinct Mechanisms.
AB  - Piwi family protein Aubergine (Aub) maintains genome integrity in late germ cells
      of the Drosophila ovary through Piwi-associated RNA-mediated repression of
      transposon activities. Although it is highly expressed in germline stem cells
      (GSCs) and early progeny, it remains unclear whether it plays any roles in early
      GSC lineage development. Here we report that Aub promotes GSC self-renewal and
      GSC progeny differentiation. RNA-iCLIP results show that Aub binds the mRNAs
      encoding self-renewal and differentiation factors in cultured GSCs. Aub controls
      GSC self-renewal by preventing DNA-damage-induced Chk2 activation and by
      translationally controlling the expression of self-renewal factors. It promotes
      GSC progeny differentiation by translationally controlling the expression of
      differentiation factors, including Bam. Therefore, this study reveals a function
      of Aub in GSCs and their progeny, which promotes translation of self-renewal and
      differentiation factors by directly binding to its target mRNAs and interacting
      with translational initiation factors.

PMID- 28441529
TI  - Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex
      to Ensure Error-Free Chromosome Segregation.
AB  - The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also
      corrects erroneous attachments that could lead to missegregation and aneuploidy.
      However, Mps1's error correction-relevant substrates are unknown. Using a
      chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes
      microtubule attachments (K fibers) epistatically to Aurora B, the other major
      error-correcting kinase. Through quantitative proteomics, we identify multiple
      sites of Mps1-regulated phosphorylation at the outer kinetochore. Substrate
      modification was microtubule sensitive and opposed by PP2A-B56 phosphatases that
      stabilize chromosome-spindle attachment. Consistently, Mps1 inhibition rescued K
      fiber stability after depleting PP2A-B56. We also identify the Ska complex as a
      key effector of Mps1 at the kinetochore-microtubule interface, as mutations that
      mimic constitutive phosphorylation destabilized K fibers in vivo and reduced the
      efficiency of the Ska complex's conversion from lattice diffusion to end-coupled
      microtubule binding in vitro. Our results reveal how Mps1 dynamically modifies
      kinetochores to correct improper attachments and ensure faithful chromosome
      segregation.

PMID- 28441531
TI  - Myrf ER-Bound Transcription Factors Drive C. elegans Synaptic Plasticity via
      Cleavage-Dependent Nuclear Translocation.
AB  - Synaptic refinement is a critical step in nervous system maturation, requiring a
      carefully timed reorganization and refinement of neuronal connections. We have
      identified myrf-1 and myrf-2, two C. elegans homologs of Myrf family
      transcription factors, as key regulators of synaptic rewiring. MYRF-1 and its
      paralog MYRF-2 are functionally redundant specifically in synaptic rewiring. They
      co-exist in the same protein complex and act cooperatively to regulate synaptic
      rewiring. We find that the MYRF proteins localize to the ER membrane and that
      they are cleaved into active N-terminal fragments, which then translocate into
      the nucleus to drive synaptic rewiring. Overexpression of active forms of MYRF is
      sufficient to accelerate synaptic rewiring. MYRF-1 and MYRF-2 are the first genes
      identified to be indispensable for promoting synaptic rewiring in C. elegans.
      These findings reveal a molecular mechanism underlying synaptic rewiring and
      developmental circuit plasticity.

PMID- 28441532
TI  - PCP and SAX-3/Robo Pathways Cooperate to Regulate Convergent Extension-Based
      Nerve Cord Assembly in C. elegans.
AB  - Formation and resolution of multicellular rosettes can drive convergent extension
      (CE) type cell rearrangements during tissue morphogenesis. Rosette dynamics are
      regulated by both planar cell polarity (PCP)-dependent and -independent pathways.
      Here we show that CE is involved in ventral nerve cord (VNC) assembly in
      Caenorhabditis elegans. We show that a VANG-1/Van Gogh and PRKL-1/Prickle
      containing PCP pathway and a Slit-independent SAX-3/Robo pathway cooperate to
      regulate, via rosette intermediaries, the intercalation of post-mitotic neuronal
      cell bodies during VNC formation. We show that VANG-1 and SAX-3 are localized to
      contracting edges and rosette foci and act to specify edge contraction during
      rosette formation and to mediate timely rosette resolution. Simultaneous loss of
      both pathways severely curtails CE resulting in a shortened, anteriorly displaced
      distribution of VNC neurons at hatching. Our results establish rosette-based CE
      as an evolutionarily conserved mechanism of nerve cord morphogenesis and reveal a
      role for SAX-3/Robo in this process.

PMID- 28441534
TI  - Managing the plant microbiome for biocontrol fungi: examples from Hypocreales.
AB  - Feeding an increasing global population requires continued improvements in
      agricultural efficiency and productivity. Meeting estimated future production
      levels requires the adoption of practices that increase output without
      environmental degradation associated with external inputs to supplement nutrition
      or control pests. Enriching the community of microbes associated with plants in
      agricultural systems for those providing ecosystem services such as pest control
      is one possible component towards achieving sustainable productivity increases.
      In this review we explore the current state of knowledge for Hypocreales fungi
      used in biological control. Advances in understanding the field ecology,
      diversity and genetic determinants of host range and virulence of hypocrealean
      fungi provide the means to improve their efficacy.

PMID- 28441533
TI  - A Global View of RNA-Protein Interactions Identifies Post-transcriptional
      Regulators of Root Hair Cell Fate.
AB  - The Arabidopsis thaliana root epidermis is comprised of two cell types, hair and
      nonhair cells, which differentiate from the same precursor. Although the
      transcriptional programs regulating these events are well studied, post
      transcriptional factors functioning in this cell fate decision are mostly
      unknown. Here, we globally identify RNA-protein interactions and RNA secondary
      structure in hair and nonhair cell nuclei. This analysis reveals distinct
      structural and protein binding patterns across both transcriptomes, allowing
      identification of differential RNA binding protein (RBP) recognition sites. Using
      these sequences, we identify two RBPs that regulate hair cell development.
      Specifically, we find that SERRATE functions in a microRNA-dependent manner to
      inhibit hair cell fate, while also terminating growth of root hairs mostly
      independent of microRNA biogenesis. In addition, we show that GLYCINE-RICH
      PROTEIN 8 promotes hair cell fate while alleviating phosphate starvation stress.
      In total, this global analysis reveals post-transcriptional regulators of plant
      root epidermal cell fate.

PMID- 28441535
TI  - Investigation of the vertical distribution and speciation of 137Cs in soil
      profiles at burnt and unburnt forest sites in the Belarusian Exclusion Zone.
AB  - The effects of fire events on contaminant radionuclides within soils of the
      Belarusian Exclusion Zone were investigated. A number of cores were taken from
      locations known to have been subject to fire events in the past as well as a
      series of cores from nearby unburnt locations. Both burnt and unburnt cores were
      analyzed for contaminant radionuclides as well as a range of relevant soil
      parameters. The distribution of 137Cs between various fractions (reversibly
      bound, irreversibly bound and insoluble) was analyzed. Results indicate no
      evidence of enhancement or enrichment of radionuclides within the soil column
      although this does not negate the possibility that such effects were evident at
      some point in the past, the fire events at two of the sites having occurred
      almost ten years earlier. Evidence was present of a persistent effect on how
      137Cs was distributed between different fractions of the soil, primarily in
      relation to the proportions associated with oxides of Fe and Mn and organic
      matter. The results of the study appear to indicate that the long-term effects of
      a forest fire on contaminant 137Cs within the soil column are expressed through
      changes in the physico-chemical forms of the nuclide to a larger extent than
      simple redistribution of the contaminant within the soil column.

PMID- 28441536
TI  - The effect of forage-types on the fatty acid profile, lipid and protein
      oxidation, and retail colour stability of muscles from White Dorper lambs.
AB  - The aim of this study was to evaluate the effect of different forage-types on
      lamb meat quality parameters. White Dorper lambs that had grazed five forage
      types, were slaughtered commercially. At 24h post-mortem, the m. longissimus
      lumborum (LL) was removed from one side, sliced into three equal sub-samples,
      vacuum packaged and assigned to ageing periods (5, 12 or 40days); the other side
      of LL was aged for 5days. The m. adductor femoris was used for fatty acid
      analysis. Lambs fed chicory+arrowleaf clover had the highest concentration of
      health claimable omega-3 fatty acids and the lowest omega-6:omega-3 fatty acid
      ratio. Forage-types with higher vitamin E content showed lower lipid oxidation
      levels independent of ageing period. Forage-type and ageing period did not
      influence the redness, yellowness, chroma or reflectance ratio (630nm/580nm) of
      displayed meat. Chicory+arrowleaf clover gave the best results to improve the
      fatty acid content of lamb meat.

PMID- 28441537
TI  - Determination of dihydralazine based on chemiluminescence resonance energy
      transfer of hollow carbon nanodots.
AB  - The famous weak chemiluminescence (CL) system of potassium permanganate and
      sodium bisulfite (KMnO4-HSO3-) was enhanced by the hollow fluorescent carbon
      nanodots (HCNs). The investigation of mechanism revealed that the enhanced CL was
      induced by the excited-state HCNs (HCNs*), which could be produced from the
      electron-transfer annihilation of positively charged HCNs (HCNs+) and negatively
      charged HCNs (HCNs-) as well as by CL resonance energy transfer (CRET) from
      excited SO2 (SO2*)/1O2 to HCNs. The dihydralazine sulfate (DHZS) had a
      diminishing effect on the CL of HCNs-KMnO4-HSO3- system due to the competitive
      consumption of O2-. Under the optimal conditions, the reduced CL signal with the
      concentration of DHZS was linear in the range of 1.0*10-7-7.0*10-5mol/L with a
      detection limit of 3.0*10-8mol/L. The relative standard deviation for seven
      repeated determination of 5.0*10-6mol/L DHZS was 2.1%. The established method was
      applied to the determination of DHZS in pharmaceutical preparations, human urine
      and plasma samples with good precision and accuracy.

PMID- 28441538
TI  - Real-time observation of cascaded electronic relaxation processes in p
      Fluorotoluene.
AB  - Ultrafast electronic relaxation processes following two photoexcitation of 400nm
      in p-Fluorotoluene (pFT) have been investigated utilizing time-resolved
      photoelectron imaging coupled with time-resolved mass spectroscopy. Cascaded
      electronic relaxation processes started from the electronically excited S2 state
      are directly imaged in real time and well characterized by two distinct time
      constants of ~85+/-10fs and 2.4+/-0.3ps. The rapid component corresponds to the
      lifetime of the initially excited S2 state, including the structure relaxation
      from the Franck-Condon region to the conical intersection of S2/S1 and the
      subsequent internal conversion to the highly excited S1 state. While, the slower
      relaxation constant is attributed to the further internal conversion to the high
      levels of S0 from the secondarily populated S1 locating in the channel three
      region. Moreover, dynamical differences with benzene and toluene of analogous
      structures, including, specifically, the slightly slower relaxation rate of S2
      and the evidently faster decay of S1, are also presented and tentatively
      interpreted as the substituent effects. In addition, photoelectron kinetic energy
      and angular distributions reveal the feature of accidental resonances with low
      lying Rydberg states (the 3p, 4s and 4p states) during the multi-photon
      ionization process, providing totally unexpected but very interesting information
      for pFT.

PMID- 28441539
TI  - A quantum-chemical insight into the tunable fluorescence color and distinct
      photoisomerization mechanisms between a novel ESIPT fluorophore and its
      protonated form.
AB  - Enol-keto proton tautomerization and cis-trans isomerization reactions of a novel
      excited-state intramolecular proton transfer (ESIPT) fluorophore of BTImP and its
      protonated form (BTImP+) were explored using density functional theory/time
      dependent density functional theory (DFT/TD-DFT) computational methods with a
      B3LYP hybrid functional and the 6-31+G(d,p) basis set. In addition, the
      absorption and fluorescence spectra were calculated at the TD-B3LYP/6-31+G(d,p)
      level of theory. Our results reveal that both BTImP and BTImP+ can undergo an
      ultrafast ESIPT reaction, giving rise to the single fluorescence emission with
      different fluorescence colors, which are nicely consistent with the experimental
      findings. Calculations also show that following the ultrafast ESIPT, BTImP and
      BTImP+ can experience the distinctly different cis-trans isomerization processes.
      The intersystem crossing between the first excited singlet S1 state and triplet
      T1 state is found to play an important role in the photoisomerization process of
      BTImP+. In addition, the energy barrier of the trans-keto->cis-keto isomerization
      in the ground state of BTImP+ is calculated to be 10.49kcalmol-1, which implies
      that there may exist a long-lived trans-keto species in the ground state for
      BTImP+.

PMID- 28441540
TI  - Supramolecular interaction of methotrexate with cucurbit[7]uril and analytical
      application.
AB  - The supramolecular interaction between cucurbit[7]uril (CB[7]) as the host and
      the anti-cancer drug methotrexate (MTX) as the guest was studied using
      fluorescence spectroscopy, UV-visible absorption spectroscopy, 1H NMR, 2D NOESY,
      and theoretical calculations. The experimental results confirmed the formation of
      1:2 inclusion complex with CB[7] and indicated a simple and sensitive competitive
      method for the fluorescence detection of MTX. It was found that the fluorescence
      intensities of CB[7]-palmatine, CB[7]-berberine and CB[7]-coptisine were quenched
      linearly upon the addition of MTX. The linear ranges obtained in the detection of
      MTX were 0.1-15MUgmL-1, 0.2-15MUgmL-1, and 0.4-15MUgmL-1 with detection limits of
      0.03MUgmL-1, 0.06MUgmL-1, and 0.13MUgmL-1, respectively. This method can be used
      for the determination of MTX in biological fluids. These results suggested that
      cucurbit[7]uril is a promising drug carrier for targeted MTX delivery and
      monitoring, with improved efficacy and reduced toxicity in normal tissues.

PMID- 28441541
TI  - Molecular interaction of 2,4-diacetylphloroglucinol (DAPG) with human serum
      albumin (HSA): The spectroscopic, calorimetric and computational investigation.
AB  - Drug molecule interaction with human serum albumin (HSA) affects the distribution
      and elimination of the drug. The compound, 2,4-diacetylphloroglucinol (DAPG) has
      been known for its antimicrobial, antiviral, antihelminthic and anticancer
      properties. However, its interaction with HSA is not yet reported. In this study,
      the interaction between HSA and DAPG was investigated through steady-state
      fluorescence, time-resolved fluorescence (TRF), circular dichroism (CD), Fourier
      transform infrared (FT-IR) spectroscopy, isothermal titration calorimetry (ITC),
      molecular docking and molecular dynamics simulation (MDS). Fluorescence
      spectroscopy results showed the strong quenching of intrinsic fluorescence of HSA
      due to interaction with DAPG, through dynamic quenching mechanism. The compound
      bound to HSA with reversible and moderate affinity which explained its easy
      diffusion from circulatory system to target tissue. The thermodynamic parameters
      from fluorescence spectroscopic data clearly revealed the contribution of
      hydrophobic forces but, the role of hydrogen bonds was not negligible according
      to the ITC studies. The interaction was exothermic and spontaneous in nature.
      Binding with DAPG reduced the helical content of protein suggesting the unfolding
      of HSA. Site marker fluorescence experiments revealed the change in binding
      constant of DAPG in the presence of site I (warfarin) but not site II marker
      (ibuprofen) which confirmed that the DAPG bound to site I. ITC experiments also
      supported this as site I marker could not bind to HSA-DAPG complex while site II
      marker was accommodated in the complex. In silico studies further showed the
      lowest binding affinity and more stability of DAPG in site I than in site II.
      Thus the data presented in this study confirms the binding of DAPG to the site I
      of HSA which may help in further understanding of pharmacokinetic properties of
      DAPG.

PMID- 28441542
TI  - Reattachment using the suture bridge augmentation for Achilles tendon avulsion
      fracture with osteoporotic bony fragment.
AB  - Although avulsion fractures of the calcaneal tuberosity are rare injuries, these
      can be a challenging problem with frequent complications, such as loss of
      reduction and soft tissue problem. Anatomical reduction and internal fixation are
      indicated to avoid these pitfalls and to restore function of the triceps surae.
      However, the best fixation device and operative technique are still
      controversial. A case that achieved satisfactory clinical outcome through a
      reattachment technique using the suture bridge augmentation for Achilles tendon
      avulsion fracture with osteoporotic bony fragment is presented.

PMID- 28441543
TI  - Simultaneous electrochemiluminescence determination of galanthamine,
      homolycorine, lycorenine, and tazettine in Lycoris radiata by capillary
      electrophoresis with ultrasonic-assisted extraction.
AB  - After ultrasonic-assisted extraction, four lycoris radiata alkaloids:
      galanthamine, homolycorine, lycorenine, and tazettine were determined by
      capillary electrophoresis electrochemiluminescence. Polyvinylpyrrolidone was
      added to the running buffer (RB) to obtain better resolution. Experimental
      conditions influencing the determination were examined, including the additives,
      detection potential, separation voltage, injection voltage and time, and RB pH
      and concentration. Under optimal experimental conditions, the baseline separation
      of the four alkaloids occurred within 16min. The proposed method displayed the
      following linear ranges (in ng/mL): galanthamine [60-5000], homolycorine [40
      5000], lycorenine [5.0-1500], and tazettine [8.0-2500]. The detection limits in
      ng/mL, (S/N=3), were galanthamine [14], homolycorine [11], lycorenine [1.8], and
      tazettine [3.1]. Intra-day and inter-day RSDs for the four alkaloids of the six
      replicates were less than 2.7% and 3.1%, respectively. The recoveries in% were:
      tazettine [102.5], lycorenine [98.20], galanthamine [97.30], and homolycorine
      [98.33].

PMID- 28441544
TI  - Enrichment of resolving power improves ion-peak quantification on a lipidomics
      platform.
AB  - In this study, we delineated the importance of MS resolving power on the ion-peak
      quantification of lipids using an Orbitrap Fusion instrument and established a
      liquid chromatography-based, high-performance lipidomics platform. The ion-peak
      recognition of several lipids in human plasma, such as LPC(15:0), LPE(22:5), and
      PC(35:0), was clearly improved by increasing the MS resolving power. In addition,
      we evaluated the impact of resolving power on the quantitative detection of
      lipids by automatic ion-peak recognition with calculation of the coefficient of
      variance (CV). The extracted ions obtained from human plasma were automatically
      annotated by Compound Discoverer software with manual confirmation of standards
      or MS2/MS3 fragments (class- and acyl side chain-specific ions and neutral
      losses). Quantitative evaluation of 499 lipids in human plasma in terms of their
      CV values clearly demonstrated an improvement in the quantitative performance by
      enriching the resolving power. Moreover, we evaluated our new lipidomics platform
      with enriched MS resolving power (setting of 240,000, full width at half maximum
      at m/z 200). Because automatic annotation by TraceFinder software overlooks
      several lipid ions, we further manually annotated additional lipid ions, which
      were confirmed by standards or MS2/MS3 fragments. Eventually, our platform
      detected 967 lipids encompassing 34 lipid classes, which were confirmed with
      standards or MS2/MS3 fragments. Of these lipids, 922 scored <20% of the CV
      values. Taken together, enriching the resolving power improved ion-peak
      quantification on our novel lipidomics platform, which enabled us to detect broad
      spectrum lipids from human plasma.

PMID- 28441545
TI  - Targeted mass spectrometry: An emerging powerful approach to unblock the
      bottleneck in phosphoproteomics.
AB  - Following the rapid expansion of the proteomics field, the investigation of post
      translational modifications (PTM) has become extremely popular changing our
      perspective of how proteins constantly fine tune cellular functions. Reversible
      protein phosphorylation plays a pivotal role in virtually all biological
      processes in the cell and it is one the most characterized PTM up to date. During
      the last decade, the development of phosphoprotein/phosphopeptide enrichment
      strategies and mass spectrometry (MS) technology has revolutionized the field of
      phosphoproteomics discovering thousands of new site-specific phosphorylations and
      unveiling unprecedented evidence about their modulation under distinct cellular
      conditions. The field has expanded so rapidly that the use of traditional methods
      to validate and characterize the biological role of the phosphosites is not
      feasible any longer. Targeted MS holds great promise for becoming the method of
      choice to study with high precision and sensitivity already known site-specific
      phosphorylation events. This review summarizes the contribution of large-scale
      unbiased MS analyses and highlights the need of targeted MS-based approaches for
      follow-up investigation. Additionally, the article illustrates the biological
      relevance of protein phosphorylation by providing examples of disease-related
      phosphorylation events and emphasizes the benefits of applying targeted MS in
      clinics for disease diagnosis, prognosis and drug-response evaluation.

PMID- 28441546
TI  - Isolation of new polyacetylenes from the roots of Eurycoma longifolia via high
      speed counter-current chromatography.
AB  - Eurycoma longifolia is a tropical plant of diverse applications in folk medicine,
      which occurs in Southeast Asia. In this study, pre-purified fraction (0.86g) of
      the crude extracts from the roots of E. longifolia, was subjected to preparative
      high-speed counter-current chromatography (HSCCC) with a two-phase solvent system
      composed of hexane-ethyl acetate-methanol-water (HEMWat) at a volume ratio of
      5:2:5:2 (v/v). Longifolione A (1, 19mg, purity 96.0%) and longifolione C (3,
      317mg, purity 96.2%), together with longifolione B (2, purity 77.6%) were
      isolated in one run. The whole mobile and stationary phase was then blown out,
      concentrated in vacuo, and subjected to second HSCCC purification. Using HEMWat
      at a volume ratio of 6:1:6:1.2 (v/v), this fraction yielded two more new
      polyacetylenenes, longifolione D (4, 5mg purity 94.5%) and longifolione E (5,
      33mg purity 96.3%). All of these five compounds are new natural products and
      isolated from E. longifolia for the first time. The established protocol for
      large-scale isolation of these polyacetylenes from E. longifolia was simple,
      efficient, and economical.

PMID- 28441547
TI  - Phthalate exposure, even below US EPA reference doses, was associated with semen
      quality and reproductive hormones: Prospective MARHCS study in general
      population.
AB  - BACKGROUND: Environment-Protection-Agency Reference Doses (EPA RfDs) for
      phthalate intakes are based on limited evidence, especially regarding low-dose
      male-reproductive toxicity. This study investigates the association between
      phthalate exposure and semen parameters and reproductive hormones in a general
      population with low phthalate exposure compared to the EPA RfDs. METHODS: The
      MARHCS (Male-Reproductive-Health-in-Chongqing-College-Students) cohort recruited
      796 male students, who experienced a relocation of campuses and shifting
      environmental exposure. Urine, semen and blood before and after the relocation
      was collected and investigated for: (1) the associations between 13 urinary
      phthalate metabolites and 11 semen/hormone outcomes (five semen parameters
      including semen volume, sperm concentration, total sperm number, progressive
      motility, normal morphology) and six serum reproductive hormones including
      estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin,
      progesterone, testosterone; (2) re-analysis of the metabolite-outcome
      associations in the subjects with estimated phthalate intakes below the RfDs; (3)
      a change in phthalate metabolites and change in semen/hormone outcomes after the
      relocation; (4) the association between these changes. RESULTS: (1) All but two
      semen/hormone outcomes were associated with at least one phthalate metabolite,
      e.g., each quartile monoethyl phthalate was associated with a 5.3%, 5.7% and 2.6%
      decrease of sperm concentration, total sperm number and progressive motility
      respectively. (2) In the subjects with phthalate intakes below the RfDs, these
      metabolite-outcome associations remained significant. (3) All metabolites except
      mono(2-ethylhexyl) phthalate declined after relocation (P<0.001 respectively); at
      the same time, semen volume, normal morphology, estradiol and luteinizing hormone
      increased (by 5.9%, 25.0%, 34.2% and 10.0%) and testosterone decreased (by 7.0%).
      (4) The changes in semen volume, normal morphology, estradiol and testosterone,
      but not the change in luteinizing hormone after relocation, were associated with
      the changes in the phthalate metabolites. CONCLUSIONS: Phthalate exposure is
      associated with interrupted semen quality and reproductive hormones in the human
      population even with a dose given below the RfDs. These effects, however, may
      only partially revert back when exposure decreases, thus emphasizing the urgency
      of stricter phthalate administration.

PMID- 28441549
TI  - Plain radiography may underestimate the burden of body packer ingestion: A case
      report.
AB  - Body packing refers to the intracorporeal concealment of illicit drugs. Here we
      report the case of a 55-year-old body packer who presented with palpitations,
      visual hallucinations, and a sense of impending death. Abdominal radiography
      demonstrated five ovoid foreign bodies overlying the rectum. At subsequent
      gastrotomy and cecotomy, thirty-eight cocaine-containing packets were retrieved
      from the stomach and ascending colon as well as from the rectum. As the
      contraband market evolves new techniques to evade detection, evaluation of the
      burden of body packer ingestion has become increasingly challenging. As
      demonstrated in this case, plain radiography can grossly underestimate the burden
      of ingestion.

PMID- 28441548
TI  - Ferrocenyl and organic novobiocin derivatives: Synthesis and their in vitro
      biological activity.
AB  - A focused series of novobiocin derivatives containing a ferrocene unit together
      with their corresponding organic novobiocin analogues have been synthesized in
      modest to good yields. These compounds were screened for biological activity
      against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human
      breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the
      general trend observed is that incorporation of the ferrocene moiety into
      novobiocin scaffold resulted in compounds 6a-d/6f showing enhanced activity
      compared to organic analogues 5a-b and 5e-f.

PMID- 28441550
TI  - Significant age, race and gender differences in global coagulation assays
      parameters in the normal population.

PMID- 28441551
TI  - Treating normal early gestation placentae with preeclamptic sera produces
      extracellular micro and nano vesicles that activate endothelial cells.
AB  - OBJECTIVES: Preeclampsia is characterised by systemic endothelial cell
      dysfunction thought to be triggered by toxic/dangerous factors from the placenta,
      including placental extracellular vesicles (EVs). Why placental EVs become toxic
      is unknown. We previously reported that preeclamptic sera produced
      toxic/dangerous placental macrovesicles but whether small EVs are also
      toxic/dangerous in preeclampsia is unknown. STUDY DESIGN: First trimester
      placental explants were treated with 10% preeclamptic or control sera (n=10) for
      24h. Micro- and nano-vesicles were harvested by sequential centrifugation. Micro-
      or nano-vesicles were also exposed to monolayers of endothelial cells in the
      presence or absence of nifedipine (50MUg/ml) or labetalol (0.5MUg/ml) which are
      well-known anti-hypertensives in clinical practices. MAIN OUTCOMES MEASURES: The
      number and size of micro- and nano-vesicles were counted. Endothelial cell
      surface intercellular adhesion molecule 1 (ICAM-1) and high mobility group box 1
      (HMGB1) levels in micro- or nano-vesicles were measured by immunoassays. RESULTS:
      Neither the amount nor size of both micro- and nano-vesicles was different after
      treating placental explants with preeclamptic or control sera. The levels of
      HMGB1 were significantly increased in both micro- and nano-vesicles from
      preeclamptic sera treated placental explants (p<0.03). Exposing endothelial cells
      to micro- or nano-vesicles from preeclamptic sera-treated placental explants
      induced endothelial activation, but it was reversed by co-incubation with
      nifedipine (p=0.004) or labetalol (p=0.002). CONCLUSION: Our data demonstrate
      that preeclamptic sera produce toxic/dangerous micro- and nano-placental EVs
      which activated endothelial cells. This effect was reversed by antihypertensives.
      The increased levels of HMGB1 in EVs may contribute to endothelial cell
      activation.

PMID- 28441552
TI  - Natural killer cell activity in women with recurrent miscarriage: Etiology and
      pregnancy outcome.
AB  - This study aimed to evaluate whether natural killer (NK) cell activity was
      associated with the etiology of recurrent miscarriage (RM), and to evaluate the
      predictive value of NK cell activity for outcomes of following pregnancies in
      women with RM. Peripheral NK cell activity was measured in 160 non-pregnant women
      with a history of two or more miscarriages. This activity was compared according
      to the etiology of RM and to pregnancy outcomes in women who became pregnant. NK
      cell activity in women with unexplained RM was significantly higher than that in
      those with known etiologies of RM. NK cell activity in women whose next
      pregnancies ended in miscarriage of fetuses with a normal chromosome karyotype
      (MN) was higher than that in those with live births (p<0.05). Women with NK cell
      activity >=33% had a higher risk for MN (relative risk 3.4, 95% confidence
      interval 1.3-8.7). An increase in peripheral NK cell activity was associated with
      MN. This increase might be involved in the pathophysiology underlying RM.

PMID- 28441553
TI  - Determination of critical operational conditions favoring sulfide production from
      domestic wastewater treated by a sulfur-utilizing denitrification process.
AB  - The aim of this study was to determine the critical operational conditions
      leading to the generation of sulfide in a domestic wastewater treated by a sulfur
      utilizing denitrification process. The influence of various important parameters
      on the reduction of the sulfates present in denitrified domestic wastewaters to
      sulfide was studied. Experiments were carried out in batch mode with denitrified
      domestic wastewaters containing various amounts of both organic matter and
      sulfates. Preliminary results showed that aqueous sulfide was generated for DOC
      and sulfate contents higher than 56 mg/L and 371 mg/L, respectively, while DOC
      and sulfate contents of 77 mg/L and 412 mg/L, respectively, were required to
      allow the release of gaseous H2S. Good correlations were also observed between
      gaseous sulfide production and the values of ORP and DOC, while the amounts of
      dissolved sulfide produced seemed to be correlated with the ORP values and the
      concentration of sulfates. Additional experiments were conducted using a Box
      Behnken methodology to determine if the production of aqueous or gaseous sulfide
      can be predicted depending on the DOC (from 50 to 90 mg/L) and sulfate contents
      (from 160 to 380 mg/L) at various temperatures ranging from 5 to 25  degrees C.
      The highest sulfide generation (H2S(g) = 84.8 ppm and H2S(aq) = 2.42 mg/L)
      occurred at 25  degrees C with DOC and sulfate concentrations starting from 90
      mg/L and 270 mg/L, respectively, indicating that the production of sulfides from
      denitrified domestic wastewaters required conditions not likely to occur at the
      effluent of a sulfur-based denitrification unit following secondary treatment.

PMID- 28441554
TI  - How far are we from closing the loop of sewage resource recovery? A real picture
      of municipal wastewater treatment plants in Italy.
AB  - This paper presents the results of a broad-scale survey of resource recovery
      implementation in Italian wastewater treatment plants (WWTPs). To the best of our
      knowledge, this is the first survey comprising a large number of WWTPs done in
      Europe: more than 600 plants were investigated, representing a treated load of
      around 20 million population equivalent (~25% of the total in Italy).
      Conventional and innovative options for both material and energy recovery along
      the water and sludge line were surveyed, in order to i) offer a real and complete
      picture of the current state of resource recovery in WWTPs, and ii) underline key
      aspects and potential areas for improvements, as a baseline for future
      developments in the direction of more sustainable plants. Survey outcomes showed
      that resource recovery is just in its infancy in sewage treatment: only 40% of
      plants perform at least one option for material/energy recovery. The action most
      often implemented is recovery of material from surplus sludge for agricultural
      purposes and the internal reuse of treated effluent as water for various types of
      plant maintenance. The production of energy from biogas also occurs frequently
      but only in large plants. On the other hand, some well-known options, such as
      external reuse of treated effluent or nutrients recovery, were implemented only
      in a minority of plants: this is likely due to limitations resulting either from
      strict regulation or difficulty placing recovered products on the market. In
      conclusion, an overall explanation of these driving forces within the system is
      explored.

PMID- 28441555
TI  - Rapid Evolution of the Cerebellum in Humans and Other Great Apes.

PMID- 28441556
TI  - Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons.

PMID- 28441557
TI  - X-ray micro computed-tomography.
AB  - Emily Baird and Gavin Taylor describe how you can make three-dimensional models
      of biological samples using x-ray micro-computed tomography.

PMID- 28441558
TI  - Polyethylene bio-degradation by caterpillars of the wax moth Galleria mellonella.
AB  - Plastics are synthetic polymers derived from fossil oil and largely resistant to
      biodegradation. Polyethylene (PE) and polypropylene (PP) represent ~92% of total
      plastic production. PE is largely utilized in packaging, representing ~40% of
      total demand for plastic products (www.plasticseurope.org) with over a trillion
      plastic bags used every year [1]. Plastic production has increased exponentially
      in the past 50 years (Figure S1A in Supplemental Information, published with this
      article online). In the 27 EU countries plus Norway and Switzerland up to 38% of
      plastic is discarded in landfills, with the rest utilized for recycling (26%) and
      energy recovery (36%) via combustion (www.plasticseurope.org), carrying a heavy
      environmental impact. Therefore, new solutions for plastic degradation are
      urgently needed. We report the fast bio-degradation of PE by larvae of the wax
      moth Galleria mellonella, producing ethylene glycol.

PMID- 28441559
TI  - Hydra: Imaging Nerve Nets in Action.
AB  - Mapping whole-brain activity during behavior represents one of the biggest and
      most exciting challenges of systems neuroscience. New research has taken
      advantage of the unique biology of an ancient organism to bring us a step closer
      to that goal.

PMID- 28441560
TI  - Evolution: Fangtastic Venoms Underpin Parasitic Mimicry.
AB  - Venomous teeth are rare in fishes, which typically utilise spines for defence. A
      new study reveals the evolutionary origins of fangs and venom in the Nemophini
      blennies and shows that, in contrast to snakes and lizards, the fangs pre-date
      the venom.

PMID- 28441561
TI  - Neural Circuits: Reduced Inhibition in Fragile X Syndrome.
AB  - The Drosophila Fragile X Syndrome model has long generated insights into this
      devastating neurological disease state. A recent study of olfactory neural
      circuitry shows that decreased lateral inhibition onto projection neurons
      relaying sensory input into higher brain centers causes impaired behavior.

PMID- 28441562
TI  - Bacterial Division: FtsZ Treadmills to Build a Beautiful Wall.
AB  - The tubulin-like FtsZ protein polymerizes into a contractile ring structure
      required for cytokinesis in most bacteria. Two new studies report that FtsZ
      polymers move around the ring by treadmilling, which guides and regulates the
      inward growth of the septal wall.

PMID- 28441563
TI  - Vision: Two Speeds in the Retina.
AB  - The central (foveal) retina takes about 30 milliseconds longer to signal to the
      brain than the peripheral retina. In the natural world, a 30 millisecond delay
      could have real consequences. Why did evolution do it this way?

PMID- 28441564
TI  - Multisensory Development: Calibrating a Coherent Sensory Milieu in Early Life.
AB  - A new study reveals the effects of visual deprivation in early life on the
      development of multisensory simultaneity perception. To understand the
      developmental processes underlying this we need to consider the multisensory
      milieu of the newborn infant.

PMID- 28441565
TI  - Gut Microbiota: Small Molecules Modulate Host Cellular Functions.
AB  - The human gut metagenome was recently discovered to encode vast collections of
      biosynthetic gene clusters with diverse chemical potential, almost none of which
      are yet functionally validated. Recent work elucidates common microbiome-derived
      biosynthetic gene clusters encoding peptide aldehydes that inhibit human
      proteases.

PMID- 28441567
TI  - Plant Development: From Dynamics to Mechanics.
AB  - A new study analyses the complex changes in shape occurring during petal
      development in snapdragon. Combining simulations with quantitative analysis leads
      to a new model, where molecular regulators control overall organ shape through
      mechanical conflicts operating at the level of entire tissues.

PMID- 28441566
TI  - Axon Degeneration: Too Much NMN Is Actually Bad?
AB  - The mechanism of axon degeneration is incompletely understood. A recent study
      demonstrates that transgenic expression of bacterial nicotinamide adenine
      mononucleotide (NMN) in zebrafish and mice, which decreases NMN levels by
      converting it to NaMN, protects against axon degeneration.

PMID- 28441568
TI  - Neuromodulation: The Fevered Mind of the Worm.
AB  - A landmark study has revealed that an interleukin-17-like signaling system
      modulates a neural circuit that controls the aggregation behavior of nematodes.

PMID- 28441570
TI  - Neural indices of phonemic discrimination and sentence-level speech
      intelligibility in quiet and noise: A P3 study.
AB  - This study examined how speech babble noise differentially affected the auditory
      P3 responses and the associated neural oscillatory activities for consonant and
      vowel discrimination in relation to segmental- and sentence-level speech
      perception in noise. The data were collected from 16 normal-hearing participants
      in a double-oddball paradigm that contained a consonant (/ba/ to /da/) and vowel
      (/ba/ to /bu/) change in quiet and noise (speech-babble background at a -3 dB
      signal-to-noise ratio) conditions. Time-frequency analysis was applied to obtain
      inter-trial phase coherence (ITPC) and event-related spectral perturbation (ERSP)
      measures in delta, theta, and alpha frequency bands for the P3 response.
      Behavioral measures included percent correct phoneme detection and reaction time
      as well as percent correct IEEE sentence recognition in quiet and in noise.
      Linear mixed-effects models were applied to determine possible brain-behavior
      correlates. A significant noise-induced reduction in P3 amplitude was found,
      accompanied by significantly longer P3 latency and decreases in ITPC across all
      frequency bands of interest. There was a differential effect of noise on
      consonant discrimination and vowel discrimination in both ERP and behavioral
      measures, such that noise impacted the detection of the consonant change more
      than the vowel change. The P3 amplitude and some of the ITPC and ERSP measures
      were significant predictors of speech perception at segmental- and sentence
      levels across listening conditions and stimuli. These data demonstrate that the
      P3 response with its associated cortical oscillations represents a potential
      neurophysiological marker for speech perception in noise.

PMID- 28441569
TI  - The Cytoskeleton-Autophagy Connection.
AB  - Actin cytoskeleton dynamics play vital roles in most forms of intracellular
      trafficking by promoting the biogenesis and transport of vesicular cargoes.
      Mounting evidence indicates that actin dynamics and membrane-cytoskeleton
      scaffolds also have essential roles in macroautophagy, the process by which
      cellular waste is isolated inside specialized vesicles called autophagosomes for
      recycling and degradation. Branched actin polymerization is necessary for the
      biogenesis of autophagosomes from the endoplasmic reticulum (ER) membrane.
      Actomyosin-based transport is then used to feed the growing phagophore with pre
      selected cargoes and debris derived from different membranous organelles inside
      the cell. Finally, mature autophagosomes detach from the ER membrane by an as yet
      unknown mechanism, undergo intracellular transport and then fuse with lysosomes,
      endosomes and multivesicular bodies through mechanisms that involve actin- and
      microtubule-mediated motility, cytoskeleton-membrane scaffolds and signaling
      proteins. In this review, we highlight the considerable progress made recently
      towards understanding the diverse roles of the cytoskeleton in autophagy.

PMID- 28441571
TI  - Negative histology with surgically treated tubal ectopic pregnancies - A
      retrospective cohort study.
AB  - OBJECTIVE: To determine the outcome of histological examinations of surgical
      specimens obtained from treatment of tubal ectopic pregnancy and to correlate
      with clinical findings, pre-operative ultrasound scans and the type of surgery.
      STUDY DESIGN: A retrospective cohort study of 941 women diagnosed with a tubal
      ectopic pregnancy in the Early Pregnancy Unit and having surgical treatment at
      King's College Hospital, London. Clinical and ultrasound data had been entered
      contemporaneously on our electronic early pregnancy database and hospital
      clinical records over an 11year period from 2004 to 2014. Demographic data,
      clinical history, ultrasound scan parameters, type of surgical management and
      histological diagnosis were recorded. The primary outcome measure was the
      presence or absence of chorionic villi in the surgical specimen. Data were
      analysed using Mann Whitney U test for non-parametric data, relative risk for
      categorical data and binomial logistic regression. RESULTS: A surgical specimen
      was obtained in 925 cases. Of these, 881/925 (95.2%) were positive for the
      presence of chorionic villi on histological examination. Patients with negative
      histology had a lower median gestational age, smaller ectopic pregnancies and
      lower serum human chorionic gonadotrophin levels. The relative risk of negative
      histology was significantly higher with a solid ectopic pregnancy on ultrasound
      (RR1.91, 95% CI 1.07-3.4) and with conservative surgery (RR 3.68, 95% CI 1.25
      10.77). The relative risk was significantly lower with the presence of embryonic
      cardiac activity (RR 0.12, 95% CI 0.02-0.85). Only the serum hCG level was a
      significant predictor of negative histology on logistic regression analysis
      (p=0.048). In 39/44 women with negative histology, the human chorionic
      gonadotrophin level declined after surgery with no further intervention. Five of
      the 44 required a second surgical procedure as the ectopic pregnancy had been
      missed at the initial surgery and did not resolve. CONCLUSION: There is lack of
      histological confirmation of sonographically diagnosed and surgically confirmed
      ectopic pregnancies in approximately 5% of cases, making this a relatively common
      finding following surgical treatment of tubal ectopic pregnancy. Clinicians
      should be aware of this when counselling women with tubal ectopic pregnancies
      about to undergo surgery, include this risk in the consent process and plan post
      surgical follow up with this in mind.

PMID- 28441572
TI  - Trait mindfulness and protective strategies for alcohol use: Implications for
      college student drinking.
AB  - INTRODUCTION: The use of Protective Behavioral Strategies (PBS) has been strongly
      linked with decreased experience of alcohol-related consequences, making them a
      potential target for intervention. Additionally, mindfulness is associated with
      decreased experience of alcohol-related consequences. The purpose of the current
      study was to evaluate a model of PBS as a mediator of the effect of mindfulness
      on alcohol-related consequences. Additionally, mindfulness as a moderator of the
      relationship between PBS and alcohol use and consequences was examined. METHODS:
      College students (N=239) at a large South Central university completed self
      report measures of demographics, alcohol use and consequences, use of PBS, and
      trait mindfulness. RESULTS: Results indicated that both higher levels of
      mindfulness and using more PBS predicted decreased alcohol-related consequences
      and consumption, with PBS mediating both relationships (p<0.01). Those with
      higher levels of mindfulness were more likely to use PBS, with individuals using
      more PBS experiencing fewer alcohol-related consequences and consuming fewer
      drinks per week. Mindfulness moderated the relationship between PBS and
      consequences, with a significantly stronger negative relationship for those with
      lower levels of mindfulness. CONCLUSIONS: Individuals who are higher in trait
      mindfulness are more likely to use PBS, which leads to a decrease in the
      experience of alcohol-related consequences. Furthermore, for individuals lower in
      mindfulness, low PBS use may lead to increased experience of alcohol
      consequences. Interventions that incorporate PBS may be most beneficial for
      students who are low in mindfulness and unlikely to engage in drinking control
      strategies.

PMID- 28441573
TI  - The role of negative affect and message credibility in perceived effectiveness of
      smokeless tobacco health warning labels in Navi Mumbai, India and Dhaka,
      Bangladesh: A moderated-mediation analysis.
AB  - OBJECTIVE: There is strong evidence showing that pictorial health warnings are
      more effective than text-only warnings. However, much of this evidence comes from
      high-income countries and is limited to cigarette packaging. Moreover, few
      studies have identified mechanisms that might explain the impact of warnings.
      METHODS: The current study examined the potential mediating role of negative
      affect and the moderating influence of message credibility in perceived
      effectiveness of smokeless tobacco warnings in two low- and middle-income
      countries (LMICs). Field interviews were conducted in India and Bangladesh, with
      adult (19+ years) smokeless tobacco users (n=1053), and youth (16-18years) users
      (n=304) and non-users (n=687). Respondents were randomly assigned to view
      warnings in one of four conditions: (1) Text-only, (2) pictorial with symbolic
      imagery, (3) pictorial with graphic images of health effects, or (4) pictorial
      with personalized graphic images plus a personal testimonial. RESULTS: The
      findings provide support for the mediating influence of negative affect in
      perceived effectiveness, for adult and youth smokeless tobacco users who viewed
      pictorial warnings (vs. text-only), and graphic health warnings (vs. personal
      testimonials). Among adults, message credibility moderated the indirect effect;
      the association was stronger when credibility was high and weaker when it was
      low. Among youth users and non-users, message credibility did not moderate the
      indirect effect. CONCLUSIONS: Consistent with research from high-income
      countries, these findings highlight the importance of selecting imagery that will
      elicit negative emotional reactions and be perceived as credible. Differential
      effects among adults and youth highlight the importance of pre-testing images.

PMID- 28441574
TI  - Surface sediment quality relative to port activities: A contaminant-spectrum
      assessment.
AB  - Ports are facing increasing environmental concerns with their importance to the
      global economy. Numerous studies indicated sediment quality deterioration in
      ports; however, the deterioration is not discriminated for each port activity.
      This study investigated a spectrum of contaminants (metals and organic
      pollutants) in surface sediments at 20 sampling points in Port Ningbo, China, one
      of the top five world ports by volume. The spectrum of contaminants (metals and
      organic pollutants) was quantified following marine sediment quality guidelines
      of China and USA and surface sediment quality was assessed according to
      thresholds of the two guidelines. Coupling a categorical matrix of port
      activities with the matrix of sedimentary contaminants revealed that contaminants
      were highly associated with the port operations. Ship repair posed a severe
      chemical risk to sediment. Operations of crude oil and coal loadings were two top
      activities related to organic pollutants in sediments while port operations of
      ore and container loadings discharged metals. Among the 20 sampling points, Cu,
      Zn, Pb, and DDT and its metabolites were the priority contaminants influencing
      sediment quality. Overall, surface sediments in Port Ningbo had relatively low
      environmental risks but ship repair is an environmental concern that must be
      addressed. This study provides a practical approach for port activity-related
      quality assessment of surface sediments in ports that could be applicable in many
      world sites.

PMID- 28441575
TI  - Estimates of recovery of the Penobscot River and estuarine system from mercury
      contamination in the 1960's.
AB  - Mercury (Hg) was discharged in the late 1960s into the Penobscot River by a chlor
      alkali production facility, HoltraChem. Using total Hg concentration profiles
      from 56 stations (58 sediment cores) in the Penobscot River (PBR), Mendall Marsh
      (MM), Orland River (OR) and Penobscot Estuary (ES), and sediment accumulation
      rates derived using detailed profiles of total Hg concentrations and radionuclide
      activities (137Cs, 239,240Pu, 210Pb), recovery from system-wide Hg pollution was
      assessed. Total Hg concentration profiles showed sharp maxima at depths
      attributed in time to a 1967 release date, and were divided into two sections:
      the first 21years (1967-1988; rapid recovery), and the recent 21years (1988-2009;
      slower recovery). The recent 21years of Hg input were used to estimate 'apparent'
      recovery rates, yielding exponentially decreasing total Hg concentrations.
      Apparent recovery half-times (T1/2=ln2/alpha) were calculated from an exponential
      fit of Hg(t)=Hg(t=21)*exp(-alpha*t)+Hg(infinity) to total Hg concentration
      profiles over the past 21years (assuming Hg(infinity) of 0, 100, or 400ngg-1).
      Mean T1/2 values were, at PBR 31years (16 of 24 cores), at MM 22years (9 of 11
      cores), at ES 20 to 120years (mean of 78years; 12 of 18 cores), and at OR 69years
      (3 of 5 cores). In 18 out of 57 cores, concentrations either increased towards
      the surface or remained the same, indicating slower or incomplete 'communication'
      with the larger system. The Penobscot River and Estuary system has recovered
      substantially since 1967, and top 1cm sediment Hg concentrations (Hg(0)) from
      areas in rapid communication with the larger system are converging to 600-700ngg
      1 (1967 maxima of 70,000+ngg-1). However, to recover from Hg(0) of 700ngg-1 to a
      Hg(infinity) of <100ngg-1 would require 3 or more half-times.

PMID- 28441576
TI  - Fate and redistribution of perfluoroalkyl acids through AFFF-impacted
      groundwater.
AB  - Leaching of perfluoroalkyl acids (PFAAs) from a local point source, a fire
      fighting training area, has led to extensive contamination of a groundwater
      aquifer which has spread underneath part of a nearby town, Oakey, situated in the
      State of Queensland, Australia. Groundwater is extracted by residents from
      privately owned wells for daily activities such as watering livestock and garden
      beds. The concentration of 10 PFAAs in environmental and biological samples
      (water, soil, grass, chicken egg yolk, serum of horses, cattle and sheep), as
      well as human serum was investigated to determine the extent of contamination in
      the town and discuss fate and redistribution of PFAAs. Perfluorooctane sulfonate
      (PFOS) was the dominant PFAA in all matrices investigated, followed by
      perfluorohexane sulfonate (PFHxS). PFOS concentrations measured in water ranged
      between <0.17-14MUg/L, concentrations of PFHxS measured between <0.07-6MUg/L.
      PFAAs were detected in backyards (soil, grass), livestock and chicken egg yolk.
      Significant differences (p<0.01) in PFOS and PFHxS concentrations in two groups
      of cattle were found, one held within the contamination plume, the other in the
      vicinity but outside of the contamination plume. In human serum PFOS
      concentrations ranged from 38 to 381MUg/L, while PFHxS ranged from 39 to
      214MUg/L. Highest PFOS concentrations measured in human serum were >30-fold
      higher compared to the general Australian population. Through use of contaminated
      groundwater secondary sources of PFAA contamination are created on private
      property, leading to further redistribution of contamination and creation of
      additional human exposure pathways.

PMID- 28441577
TI  - Membrane vesicles and horizontal gene transfer in prokaryotes.
AB  - Membrane vesicles (MVs) are released from all living cells. MVs are lumen
      containing spheres of lipid-bilayers derived from the cell surface. MVs are
      biologically active and contain various components, including genetic material.
      Both chromosomal and plasmid DNA, as well as different types of RNA have been
      detected in MVs. Vesicle-mediated transfer of genes coding for antibiotic
      resistance, virulence and metabolic traits has been reported in Gram-negative and
      Gram-positive bacteria and in Archaea. MVs can persist over time in natural
      environments. Here we review the characteristics of and the role of MVs in
      horizontal gene transfer (HGT) processes in prokaryotes.

PMID- 28441578
TI  - Preoperative radiation therapy: The 'new' targeted breast cancer treatment?

PMID- 28441579
TI  - Geldanamycin-inspired compounds induce direct trans-differentiation of human
      mesenchymal stem cells to neurons.
AB  - Inspired from geldanamycin, the synthesis of a new series of 20-membered
      macrocyclic compounds is developed. The key features in our design are (i)
      retention of the fragment having the precise chiral functional groups of
      geldanamycin at C10, C11, C12 and C14, and (ii) replacement of an olefin moiety
      with the ester group, and the quinoid sub-structure with the triazole ring. The
      southern fragment needed for the macrocyclic ring formation was obtained from
      Evans' syn aldol as the key reaction and with the use of D-mannitol as the cheap
      source of a chiral starting material. For the synthesis of the northern fragment,
      we utilized l-ascorbic acid, which provided the desired chiral functional groups
      at C6 and C7. Further, the chain extension completed the synthesis of the
      northern fragment. In our approach, the crucial 20 membered macrocyclic ring was
      formed employing the click chemistry. When tested for their ability to directly
      trans-differentiate human mesenchymal stem cells to neurons, two novel compounds
      (20a and 7) from this series were identified and this was further validated by
      the presence of specific neuronal biomarkers (i.e. nestin, agrin and RTN4).

PMID- 28441580
TI  - The computer-aided discovery of novel family of the 5-HT6 serotonin receptor
      ligands among derivatives of 4-benzyl-1,3,5-triazine.
AB  - The work describes a discovery of new chemical family of potent ligands for the 5
      HT6 serotonin receptors. During the search for new histamine H4 receptor
      antagonists among 1,3,5-triazine derivatives, compound 2 (4-benzyl-6-(4
      methylpiperazin-1-yl)-1,3,5-triazin-2-amine) was found. Compound 2, weakly active
      for the H4 receptor but fitted in 3/4 of pharmacophore features of the 5-HT6R
      ligand, occurred to be a moderate 5-HT6R agent, useful as a lead structure for
      further modifications. A series of new derivatives (3-19) of the lead 2 was
      synthesized, evaluated in the radioligand binding assay (RBA) and explored in
      comprehensive molecular modelling, including both pharmacophore- and structure
      based approaches with docking to the homology model of 5-HT6R. The most active
      compounds displayed a potent affinity for the 5-HT6R in the nanomolar range (Ki =
      20-30 nM), some of them (4, 11 and 19) were tested in the rat forced swim test
      that revealed their antidepressant-like effect. SAR-analysis on the basis of
      both, RBA and docking results, indicated that action on the receptor is related
      to the hydrophobicity and the size of aromatic moiety substituted by a methylene
      linker at the position 4 of 1,3,5-triazine.

PMID- 28441581
TI  - Design, combinatorial synthesis and biological evaluations of novel 3-amino-1'
      ((1-aryl-1H-1,2,3-triazol-5-yl)methyl)-2'-oxospiro[benzo[a] pyrano[2,3
      c]phenazine-1,3'-indoline]-2-carbonitrile antitumor hybrid molecules.
AB  - A combinatorial chemical library of fifty-nine novel 3-amino-1'-((1-aryl-1H-1,2,3
      triazol-5-yl)methyl)-2'-oxospiro[benzo[a]pyrano[2,3-c]phenazine-1,3'-indoline]-2
      carbonitrile, designed as hybrid molecules of phenazine, pyran, indole and 1,2,3
      triazole pharmacophores, were constructed in this study. Cytotoxic evaluation
      indicated that some compounds exhibited moderate cytotoxicity against HCT116,
      MCF7, HepG2 and A549 cancer cell lines in vitro, in which compound 36 was found
      to have best antiproliferative activity against the A549 cancer cell line with
      IC50 value of 5.4 MUM. All compounds had low or no effect against L02 and HUVEC
      non-cancer cell lines. Compound 36 was further confirmed to mainly locate
      mitochondria in A549 cancer cells via laser-scanning confocal microscopy.
      Moreover, compound 36 was proved to increase ROS production and induce cell cycle
      arrest in S phase. Western blot analysis illustrated Bax/Bcl-2 ratio was
      increased at dose-dependent manner, and both cleaved caspase-3 and cleaved
      caspase-9 was enhanced by treated with compound 36. All the above evidences in
      vitro indicated that compound 36 might induce the apoptosis of A549 cancer cells
      via a mitochondria-dependent pathway.

PMID- 28441582
TI  - Synthesis and antiproteasomal activity of novel O-benzyl salicylamide-based
      inhibitors built from leucine and phenylalanine.
AB  - Inhibition of protein degradation is one of strategies for suppression of
      uncontrolled proliferation of cancer cells. Proteolytic degradation in cells is
      mainly ensured by proteasome and its inhibition by bortezomib showed benefit in
      clinical use for the treatment of multiple myeloma. We report here the library of
      antiproteasomal O-benzyl salicylamides built from leucine and phenylalanine.
      Prepared compounds displayed antiproliferative activity on K562, CEM and U266
      cancer cell lines, ranging from high micromolar to submicromolar GI50 values. The
      most potent compounds (series 4 and 6) were further assayed for their inhibition
      of chymotrypsin-like protease activity of the 26S proteasome in U266 cells. The
      majority of compounds inhibited the proteasome in mid-nanomolar concentrations
      (IC50 ranging from 57 to 197 nM) and it correlated with cellular potency. In a
      cell based assay involving green fluorescence protein (GFP) fused to a short
      degron that is rapidly degraded by a proteasome the compounds induced
      accumulation of GFP, visualised and quantified by live-cell imaging. Levels of
      polyubiquitinated proteins in U266 cells treated by compound 4m were also
      analyzed by immunoblotting, revealing a typical high molecular mass smear of
      ubiquitin conjugates. Finally, apoptotic cell death in treated U266 cells was
      detected biochemically by measuring the activity of caspases 3 and 7 in lysates
      and by immunoblotting of caspase 7, its substrate poly(ADP-ribose)polymerase, and
      Mcl-1, which all together showed changes typical for apoptosis. All these
      observations were in agreement with expected cellular mechanism of action and
      confirmed proteasome targeting by prepared O-benzyl salicylamides.

PMID- 28441583
TI  - Randomized controlled trial of repetitive transcranial magnetic stimulation
      combined with paroxetine for the treatment of patients with first-episode major
      depressive disorder.
AB  - Repetitive transcranial magnetic stimulation (rTMS) has been introduced as a new
      and effective treatment option for major depression. This paper examined the
      effectiveness of rTMS on first episode depressed patients when combined with
      antidepressant drugs. A random sample of forty-three first-episode depressed
      patients received active or sham rTMS to the left dorsolateral prefrontal cortex,
      and concomitantly took paroxetine for 4 weeks, and paroxetine monotherapy for 4
      weeks afterwards. Response was defined as a >=50% decrease on the total Hamilton
      Depression Rating Scale (HDRS) from the baseline, and remission was defined as an
      HDRS total residual score <8. The dosage of paroxetine was the average dose per
      day in each week. Repeated-measures ANOVA revealed a significant improvement in
      the HDRS with active compared with sham rTMS from the end of the 1st week to the
      4th week. At the end of the 4th week, response rate was 95.5% with active and
      71.4% with sham rTMS, remission rate was 68.2% with active and 38.1% with sham
      rTMS, while these significant differences disappeared at the endpoint of the
      study. These findings indicate that rTMS at 10-Hz accelerated the onset of action
      and augmented the response to paroxetine for first-episode depressed patients.

PMID- 28441584
TI  - The efficacy and safety of aripiprazole for tic disorders in children and
      adolescents: A systematic review and meta-analysis.
AB  - The aims are to evaluate the efficacy and safety of aripiprazole for tic
      disorders (TDs) in children and adolescents. We searched PubMed, Embase,
      PsychINFO, Cochrane database as well as Chinese databases of CNKI, VIP, CBM and
      Wanfang from the database inception to October 2016, and 17 full-text studies
      (N=1305) were included in our article. The meta-analysis of 10 studies (N=817)
      showed that there was no significant difference in the reduction of total YGTSS
      score between aripiprazole and other drugs, and meta-analysis of 7 studies
      (n=324) which used tic symptom control ?30% as outcome measure showed that there
      was no significant difference between aripiprazole and other treatments. The most
      common AEs of aripiprazole were the drowsiness, nausea/vomiting and increased
      appetite, and meta analysis which used the TESS scale as the outcome measurement
      showed that there was a significant difference between aripiprazole and
      haloperidol. In conclusion, these data provide moderate quality evidence that
      aripiprazole could be an effective and safe treatment option for TDs, and results
      from further trials are urgently needed to extend this evidence base.

PMID- 28441585
TI  - Assessing the latent structure of DSM-5 PTSD among Chinese adolescents after the
      Ya'an earthquake.
AB  - To examine the underlying substructure of DSM-5 PTSD in an adolescent sample,
      this study used a confirmatory factor analysis alternative model approach to
      assess 813 adolescents two and a half years after the Ya'an earthquake.
      Participants completed the PTSD Checklist for DSM-5, the Center for Epidemiologic
      Studies Depression Scale for Children, and the Screen for Child Anxiety Related
      Emotional Disorders. The results found that the seven-factor hybrid PTSD model
      entailing intrusion, avoidance, negative affect, anhedonia, externalizing
      behaviors, anxious arousal, and dysphoric arousal had significantly better fit
      indices than other alternative models. Depression and anxiety displayed high
      correlations with the seven-factor model. The findings suggested that the seven
      factor model was more applicable to adolescents following the earthquake, and may
      carry important implications for further clinical practice and research on
      posttraumatic stress symptomatology.

PMID- 28441586
TI  - Kobuvirus VP3 protein restricts the IFN-beta-triggered signaling pathway by
      inhibiting STAT2-IRF9 and STAT2-STAT2 complex formation.
AB  - Emerged porcine kobuvirus (PKV) has adversely affected the global swine industry
      since 2008, but the etiological biology of PKV is unclear. Screening PKV-encoded
      structural and non-structural proteins with a type I IFN-responsive luciferase
      reporter showed that PKV VP3 protein inhibited the IFN-beta-triggered signaling
      pathway, resulting in the decrease of VSV-GFP replication. QPCR data showed that
      IFN-beta downstream cytokine genes were suppressed without cell-type specificity
      as well. The results from biochemical experiments indicated that PKV VP3
      associated with STAT2 and IRF9, and interfered with the formation of the STAT2
      IRF9 and STAT2-STAT2 complex, impairing nuclear translocation of STAT2 and IRF9.
      Taken together, these data reveal a new mechanism for immune evasion of PKV.

PMID- 28441587
TI  - Epidermoid cyst of the spleen, a case report.
AB  - INTRODUCTION: Splenic tumors are rare and are either primary or secondary, benign
      or malignant. Most have none to minimal symptomatology and are found
      incidentally. Splenic cysts can be infectious, congenital, or traumatic.
      Epidermoid cysts and parasitic cysts are examples of primary cysts and usually
      have a classic presentation on imaging. Despite advanced imaging modalities and
      patient's clinical presentation, it can be difficult to diagnose an epidermoid
      cyst without histological examination. The purpose of this paper is to discuss
      typical findings of primary splenic cysts on imaging, but how they may differ in
      appearance. PRESENTATION OF CASE: 51 year old female who presented with vague
      abdominal discomfort and was found to have a large splenic mass with cystic
      components on imaging which did not demonstrate a typical primary splenic cyst
      appearance. Patient underwent an uneventful hand-assisted laparoscopic total
      splenectomy and had an uneventful recovery with histopathology revealing an
      epidermoid splenic cyst. CONCLUSION: Primary splenic cysts are difficult to
      diagnose and differentiate with imaging alone. They have a variable presentation
      and can present like as a cystic mass. It is important to include them in the
      differential diagnosis of splenic masses since histopathology is the final
      determinant of the diagnosis.

PMID- 28441588
TI  - Reduced ENA78 levels as novel biomarker for major depressive disorder and
      venlafaxine efficiency: Result from a prospective longitudinal study.
AB  - Although lines of evidence demonstrated that cytokines play an important role in
      the pathogenesis of major depressive disorder (MDD), none of the them have been
      established as reliable biomarkers. We use our previous whole-genome cRNA
      microarray data to identify epithelial cell-derived neutrophil-activating peptide
      78 (ENA78), the most differentially expressed cytokine in peripheral blood
      between MDD patients and healthy controls; and then we confirmed the result by
      the quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and
      enzyme-linked immunosorbent assay (ELISA) for mRNA and protein level,
      respectively, in an independent drug-naive first-episode sample set. In addition,
      to replicate the role of plasma ENA 78 in MDD, and determine the role of ENA78 on
      the venlafaxine efficiency, we further detected the plasma ENA78 in another
      independent 8- week follow-up sample set. We found that both of mRNA and plasma
      of ENA78 decreased in MDD patients, and displayed much lower after venlafaxine
      treatment. We also found that venlafaxine non-responders had lower level of
      peripheral plasma ENA78 prior to treatment than responders. Our findings for the
      first time provided strong evidence that the ENA78 may play a key role of
      mediator in pathogenesis of MDD and in the mechanism of vinlafaxine effects on
      MDD indicating that reduced ENA78 may be a potential biomarker for diagnosing of
      MDD and predicting of response to venlafaxine.

PMID- 28441589
TI  - Nutrient stress-induced chromatin changes in plants.
AB  - The ability of plants to appropriately respond to the soil nutrient availability
      is of primary importance for their development and to complete their life cycle.
      Deciphering these multifaceted adaptive mechanisms remains a major challenge for
      scientists to date. Recent technological breakthroughs now enable to assess the
      dynamism and complexity of these processes at unprecedented resolution. In this
      review, we present some of the most recent findings on the involvement of histone
      modifications, histone variants and DNA methylation in response to nutrient
      stresses as well as discussing the potential roles these chromatin changes could
      serve as priming or as trans-generational stress memory mechanisms.

PMID- 28441590
TI  - Screening Arabidopsis mutants in genes useful for phytoremediation.
AB  - Emissions of heavy metals have risen over the past 200 years and significantly
      exceed those from natural sources. Phytoremediation strategies may be able to
      recover soil productivity in self-sustaining ecosystems; however, our knowledge
      of the molecular mechanisms involved in plant heavy-metal perception and
      signalling is scarce. The aim of this study was to assemble a "molecular tool
      box" of genes useful for phytoremediation. To identify mutants with different
      heavy-metal-tolerance, we first selected a medium from mixtures containing three
      metals based on their presence in two Spanish mining areas and then screened
      about 7000 lines of Arabidopsis T-DNA mutants and found 74 lines more resistant
      and 56 more susceptible than the wild type (WT). Classification of the genes
      showed that they were mainly linked to transport, protein modification and
      signalling, with RNA metabolism being the most representative category in the
      resistant phenotypes and protein metabolism in the sensitive ones. We have
      characterized one resistant mutant, Athpp9 and one sensitive, Atala4. These
      mutants showed differences in growth and metal translocation. Additionally, we
      found that these mutants keep their phenotype in amended former soils, suggesting
      that these genes may be useful for phytoremediation and the recovery of
      contaminated soils.

PMID- 28441591
TI  - Preliminary study of possible relationships between exposure to PCDD/Fs and dl
      PCBs in ambient air and the length of life of people.
AB  - There is a lack of studies on the impact of very toxic and persistent organic
      compounds as polychlorinated dibenzodioxins (PCDDs), dibenzofurans (PCDFs) and
      polychlorinated biphenyls (PCBs) on the population life expectancy. Preliminary
      studies on the relations between exposure to PCDD/Fs and dl-PCBs in ambient air
      and the length of life of residents of 12 cities (2 million people) in the
      Silesia province has been undertaken. The average length of life of inhabitants
      in 12 cities of Silesia province was calculated on the basis of register of
      deaths after excluding deaths caused by external causes and the concentration of
      PCDD/Fs and dl-PCBs were measured. The studies have shown that inhalation
      exposure to dioxins, furans and dl-PCBs could be an important factor which may
      shorten the life expectancy of the population. The results of preliminary studies
      indicate a strong correlation between the concentration of PCDD/Fs and dl-PCBs in
      the ambient air and the length of life of women. The conducted analysis of the
      regression shows that reduction of chlorinated persistent organic compounds of
      10fg I-TEQ/m3 could extend life expectancy of women by approximately 4months
      (0.3years).

PMID- 28441592
TI  - Characterization of major natural and anthropogenic source profiles for size
      fractionated PM in Yangtze River Delta.
AB  - Samples of size-fractionated particles were collected from local natural and
      anthropogenic sources in two industrial cities in the Yangtze River Delta, using
      either grab/resuspension sampling or ambient air sampling. The chemical
      characterizations of twenty one source profiles were obtained, based on elements
      (Al, As, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Pb and Zn), soluble ions (Cl-, NO3-,
      SO42-, NH4+, K+, Na+ and Ca2+) and carbonaceous material such as organic carbon
      (OC) and elemental carbon (EC). The profiles vary between sources from different
      areas, as well as between different particulate sizes. Results show that
      particulate matter that originated as soil dust, construction dust and fugitive
      dust is typically rich in crustal elements, especially Al, Ca, Fe and Mg, while
      the presence of calcium is found to be a hallmark of the cement industry and
      ceramic industry. Dominant compositions of particles from coal-fired power plants
      are variable, with OC ranging from 2.2%-27%. Garbage-fired power plant and
      cooking smoke particulate emissions are enriched in Na, Cl-, OC and K due to the
      presence of salty and organic matter. The element Fe, ranging from 6.1% to 26.0%,
      is found to be an important marker for steel production dust. Vehicle exhaust
      profiles are characterized by high abundances of OC (12.1%-53.6%) and EC (3.9%
      20.0%). Burning of straw results in K (1.6%-7.2%) and OC (12.4%-25.9%) being the
      dominant composition. Preliminary work has also been done on establishing local
      industrial profiles such as textile, ceramic and electroplating industries. This
      work could be used in receptor model studies to estimate the contributions of
      different sources to the size-fractionated particulate matter in the Yangtze
      River Delta.

PMID- 28441593
TI  - A comprehensive evaluation of the environmental quality of a coastal lagoon
      (Ravenna, Italy): Integrating chemical and physiological analyses in mussels as a
      biomonitoring strategy.
AB  - This study aimed at evaluating the environmental quality of a coastal lagoon
      (Pialassa Piomboni, NW-Adriatic, Italy) by combining analyses of biomarkers of
      environmental stress and bioaccumulation of contaminants in marine mussels
      (Mytilus galloprovincialis) transplanted for 28days to six selected sites.
      Assessed biomarkers encompassed lysosomal endpoints, oxidative stress and
      detoxification parameters, specific responses to metals, neuro- and genotoxic
      substances; chemical analyses focused on PAHs, metals, pesticide and
      pharmaceuticals. Results showed up to a 67-fold bioaccumulation of 4- to 6-ring
      PAHs, including pyrene, fluoranthene, chrysene and benzo(ghi)perylene in
      transplanted mussels compared to reference conditions (T0). A 10-fold increase of
      Fe, Cr and Mn was observed, while pesticides and pharmaceuticals were not or
      slightly detected. The onset of a significant (p<0.05) general stress syndrome
      occurred in exposed mussels, as outlined by a 50-57.7% decrease in haemocytes
      lysosomal membrane stability and an increased lysosomal volume (22.6-26.9%) and
      neutral lipid storage (18.9-48.8%) observed in digestive gland. Data also
      revealed a diffuse lipofuscin accumulation (86.5-139.3%; p<0.05) in digestive
      gland, occasionally associated to a catalase activity inhibition in gill,
      indicating an increased vulnerability toward pro-oxidant factors. Higher levels
      of primary DNA damage (258%; p<0.05) and PAH accumulation were found in mussels
      exposed along the eastern shoreline, hosting a petrochemical settlement.
      Bioaccumulated metals showed a positive correlation with increased
      metallothionein content (85-208%; p<0.05) observed in mussels from most sites.
      Overall, the use of physiological and chemical analyses detected chronic
      alterations of the mussel health status induced by specific toxicological
      pathways, proving a suitable approach in the framework of biomonitoring programs
      of coastal lagoons.

PMID- 28441594
TI  - Cotransport of human adenoviruses with clay colloids and TiO2 nanoparticles in
      saturated porous media: Effect of flow velocity.
AB  - This study focuses on the effects of two clay colloids (kaolinite, KGa-1b and
      montmorillonite, STx-1b) and titanium dioxide (TiO2) nanoparticles (NPs) on human
      adenovirus transport and retention in water saturated porous media at three
      different pore water velocities (0.38, 0.74, and 1.21cm/min). Transport and
      cotransport experiments were performed in 30-cm long laboratory columns packed
      with clean glass beads with 2mm diameter. The experimental results suggested that
      the presence of KGa-1b, STx-1b and TiO2 NPs increased human adenovirus
      inactivation and attachment onto the solid matrix, due to the additional
      attachment sites available. Retention by the packed column was found to be
      highest (up to 99%) in the presence of TiO2 NPs at the highest pore water
      velocity, and lowest in the presence of KGa-1b. The experimental results
      suggested that adenoviruses would undergo substantial aggregation or
      heteroaggregation during cotransport. However, no distinct relationships between
      mass recoveries and water velocity could be established from the experimental
      cotransport data. Note that for the cotransport experiments, collision efficiency
      values were shown to be higher for the higher flow rate examined in this study.

PMID- 28441595
TI  - Modelling drivers and distribution of lead and zinc concentrations in soils of an
      urban catchment (Sydney estuary, Australia).
AB  - The human population is increasing globally and land use is changing to
      accommodate for this growth. Soils within urban areas require closer attention as
      the higher population density increases the chance of human exposure to urban
      contaminants. One such example of an urban area undergoing an increase in
      population density is Sydney, Australia. The city also possesses a notable
      history of intense industrial activity. By integrating multiple soil surveys and
      covariates into a linear mixed model, it was possible to determine the main
      drivers and map the distribution of lead and zinc concentrations within the
      Sydney estuary catchment. The main drivers as derived from the model included
      elevation, distance to main roads, main road type, soil landscape, population
      density (lead only) and land use (zinc only). Lead concentrations predicted using
      the model exceeded the established guideline value of 300mgkg-1 over a large
      portion of the study area with concentrations exceeding 1000mgkg-1 in the south
      of the catchment. Predicted zinc did not exceed the established guideline value
      of 7400mgkg-1; however concentrations were higher to the south and west of the
      study area. Unlike many other studies we considered the prediction uncertainty
      when assessing the contamination risk. Although the predictions indicate
      contamination over a large area, the broadness of the prediction intervals
      suggests that in many of these areas we cannot be sure that the site is
      contaminated. More samples are required to determine the contaminant distribution
      with greater precision, especially in residential areas where contamination was
      highest. Managing sources and addressing areas of elevated lead and zinc
      concentrations in urban areas has the potential to reduce the impact of past
      human activities and improve the urban environment of the future.

PMID- 28441596
TI  - Individual variation of persistent organic pollutants in relation to stable
      isotope ratios, sex, reproductive phase and oxidative status in Scopoli's
      shearwaters (Calonectris diomedea) from the Southern Mediterranean.
AB  - Little is known about the accumulation of persistent organic pollutants (POPs)
      and its consequences for seabirds in the Mediterranean basin. We characterised
      the plasma contaminant profile (polychlorinated biphenyls SigmaPCBs;
      organochlorine pesticides SigmaOCPs; polybrominated diphenyl ethers SigmaPBDEs)
      of a population of the seabird Scopoli's shearwater (Calonectris diomedea) that
      breeds in the southern Mediterranean (Linosa Island) and investigated (i) whether
      sex, stable isotope ratios (related to diet), reproductive phase (early
      incubation vs. late breeding season) and body mass explained variation in
      contaminant burden and (ii) whether they predict health-related variables. The
      predominant category of POPs was SigmaPCBs contributing between 53.0 and 92.4% of
      the total POPs in each shearwater. The percentage contribution of SigmaOCPs to
      total POPs ranged between 7.6 and 47.0%, while that of SigmaPBDEs ranged between
      <1% and 22.1%. Near the end of the breeding season, concentrations of SigmaPCBs,
      SigmaOCPs and SigmaPOPs were significantly higher than at the beginning of the
      incubation period. SigmaPBDEs were higher in males than females near the end of
      the breeding season, while they were higher in females than males at the
      beginning of the egg incubation period. Carbon- and nitrogen isotope ratios and
      individual body mass were not significantly associated with any contaminant
      class. Mates differed in the concentration of POPs, but they had similar stable
      isotope values. There was little evidence for a connection between contaminants
      and blood-based markers of oxidative balance. None of the contaminants predicted
      the probability of a bird being resighted as a breeder the following year. Thus,
      although POPs were present at high concentrations in some individuals, our study
      suggests little concern regarding POP exposure for this shearwater population.

PMID- 28441597
TI  - Differences in nitrate and phosphorus export between wooded and grassed riparian
      zones from farmland to receiving waterways under varying rainfall conditions.
AB  - Agricultural activities in catchments can cause excessive nutrient loads in
      waterways. Catchment nitrogen (N) and phosphorus (P) flows may be intercepted and
      assimilated by riparian vegetation. While prior studies suggest that woody
      vegetation is preferable for reducing P loads, the question remains: is woody
      vegetation or grass cover more effective at reducing catchment N and P exports to
      waterways. To address this we investigated the relative importance of vegetation
      type, hydrologic and soil microbial processes on N and P losses from soil to a
      stream. The study involved the analysis of data from two soil microcosm
      experiments, and a field case study. We found P leaching loss from riparian zones
      depended significantly on vegetation type (woody vs. grass cover), with lower P
      exported from wooded riparian zones, irrespective of the scale of rainfall. For N
      leaching losses, the scale of rainfall had an effect. During high rainfall,
      vegetation type had a major effect on N leaching loss, with lower N exported from
      grassed verses wooded riparian zones. However, under low rainfall conditions,
      soil type and soil C and N stores, potential indicators of soil microbial
      activity, rather than vegetation cover, affected N leaching. It is hypothesized
      that soil microbes were reducing N removal under these conditions. We reason that
      nitrifiers may have played an important role in soil N cycling, as increased soil
      ammonium had a strong positive effect on nitrate leaching loads, mediated through
      soil nitrate stores. Whereas, N immobilization, via incorporation into microbial
      biomass, and denitrification processes appeared to be limited by C availability,
      with increased C associated with reduced N leaching. Overall, this study
      identified that N leaching losses from riparian zones appeared to be affected by
      two different processes, vegetative uptake and soil microbial processes, the
      relative importance of which was driven by hydrological conditions.

PMID- 28441598
TI  - Hypertension modifies the short-term effects of temperature on morbidity of
      hemorrhagic stroke.
AB  - BACKGROUND: This study estimated the effects of ambient temperature on hospital
      admissions for hemorrhagic stroke during 2004-2009 in Jinan, China, and the
      effect modification of hypertension status. METHODS: The exposure-response
      relationship between temperature and hemorrhagic stroke was firstly examined, and
      then the association between daily mean temperature and hemorrhagic stroke was
      investigated using a generalized additive model. Stratified analyses were
      conducted to examine the potential effect modification of hypertension. RESULTS:
      A total of 1577 hemorrhagic stroke cases were observed between 2004 and 2009,
      among which, 1058 were hypertensive and 519 were non-hypertensive. We found an
      approximately linear relationship between ambient temperature and hemorrhagic
      stroke. Each 1 degrees C decrease in the current day's temperature was associated
      with 1.63% (95% CI: 0.33%, 2.95%) increase in daily hemorrhagic stroke. The
      stratified analyses observed that the association was significant among
      hypertensive hemorrhagic stroke, each 1 degrees C decrease in the current day's
      temperature was associated with 2.26% (95% CI: 0.57%, 3.98%) increase in daily
      hypertensive hemorrhagic stroke. While no significant effect was observed for non
      hypertensive hemorrhagic stroke. CONCLUSIONS: Low temperature might be one risk
      factor for hemorrhagic stroke and hypertension may be one effect modifier of this
      association in Jinan, China.

PMID- 28441599
TI  - Transport and attenuation of Salmonella enterica, fecal indicator bacteria and a
      poultry litter marker gene are correlated in soil columns.
AB  - Millions of tons of fecal-contaminated poultry litter are applied to U.S.
      agricultural fields annually. Precipitation and irrigation facilitate transport
      of fecal-derived pathogens and fecal indicator bacteria (FIB) to groundwater. The
      goal of this study was to compare transport of pathogens, FIB, and a microbial
      source tracking marker gene for poultry litter (LA35) in a simulated soil-to
      groundwater system. Nine laboratory soil columns containing four different soil
      types were used to evaluate microbial transport to groundwater via infiltration.
      Quantitative polymerase chain reaction was used to monitor Salmonella enterica
      Typhimurium, Escherichia coli, Enterococcus spp., Brevibacterium sp. LA35 and
      Bacteroidales leached from soil columns inoculated with poultry litter. S.
      enterica was correlated with LA35 poultry litter marker gene and FIB
      concentrations in column soils containing organic matter, but not in acid washed
      sands. In contrast, S. enterica was found to correlate with LA35 and FIB in the
      leachate from columns containing sand, but not with leachate from organic soil
      columns. The majority of recovered DNA was found in leachate of predominately
      sandy soil columns, and in the soil of loamy columns. At least 90% of the DNA
      retained in soils for each microbial target was found in the top 3cm of the
      column. These studies suggest that poultry litter associated pathogens and FIB
      are rapidly released from litter, but are influenced by complex attenuation
      mechanisms during infiltration, including soil type. This study advances our
      understanding of the potential for subsurface transport of poultry litter
      associated pathogens and FIB, and support the use of the LA35 marker gene for
      evaluating poultry litter impacts on groundwater.

PMID- 28441600
TI  - Microplastics in the Antarctic marine system: An emerging area of research.
AB  - It was thought that the Southern Ocean was relatively free of microplastic
      contamination; however, recent studies and citizen science projects in the
      Southern Ocean have reported microplastics in deep-sea sediments and surface
      waters. Here we reviewed available information on microplastics (including
      macroplastics as a source of microplastics) in the Southern Ocean. We estimated
      primary microplastic concentrations from personal care products and laundry, and
      identified potential sources and routes of transmission into the region.
      Estimates showed the levels of microplastic pollution released into the region
      from ships and scientific research stations were likely to be negligible at the
      scale of the Southern Ocean, but may be significant on a local scale. This was
      demonstrated by the detection of the first microplastics in shallow benthic
      sediments close to a number of research stations on King George Island.
      Furthermore, our predictions of primary microplastic concentrations from local
      sources were five orders of magnitude lower than levels reported in published
      sampling surveys (assuming an even dispersal at the ocean surface). Sea surface
      transfer from lower latitudes may contribute, at an as yet unknown level, to
      Southern Ocean plastic concentrations. Acknowledging the lack of data describing
      microplastic origins, concentrations, distribution and impacts in the Southern
      Ocean, we highlight the urgent need for research, and call for routine,
      standardised monitoring in the Antarctic marine system.

PMID- 28441601
TI  - Improving understanding of mixed-land-use watershed suspended sediment regimes:
      Mechanistic progress through high-frequency sampling.
AB  - Given the importance of suspended sediment to biogeochemical functioning of
      aquatic ecosystems, and the increasing concern of mixed-land-use effects on
      pollutant loading, there is an urgent need for research that quantitatively
      characterizes spatiotemporal variation of suspended sediment dynamics in
      contemporary watersheds. A study was conducted in a representative watershed of
      the central United States utilizing a nested-scale experimental watershed design,
      including five gauging sites (n=5) partitioning the catchment into five sub
      watersheds. Hydroclimate stations at gauging sites were used to monitor air
      temperature, precipitation, and stream stage at 30-min intervals during the study
      (Oct. 2009-Feb. 2014). Streamwater grab samples were collected four times per
      week, at each site, for the duration of the study (Oct. 2009-Feb. 2014). Water
      samples were analyzed for suspended sediment using laser particle diffraction.
      Results showed significant differences (p<0.05) between monitoring sites for
      total suspended sediment concentration, mean particle size, and silt volume.
      Total concentration and silt volume showed a decreasing trend from the primarily
      agricultural upper watershed to the urban mid-watershed, and a subsequent
      increasing trend to the more suburban lower watershed. Conversely, mean particle
      size showed an opposite spatial trend. Results are explained by a combination of
      land use (e.g. urban stormwater dilution) and surficial geology (e.g. supply
      controlled spatial variation of particle size). Correlation analyses indicated
      weak relationships with both hydroclimate and land use, indicating non-linear
      sediment dynamics. Suspended sediment parameters displayed consistent seasonality
      during the study, with total concentration decreasing through the growing season
      and mean particle size inversely tracking air temperature. Likely explanations
      include vegetation influences and climate-driven weathering cycles. Results
      reflect unique observations of spatiotemporal variation of suspended sediment
      particle size class. Such information is crucial for land and water resource
      managers working to mitigate aquatic ecosystem degradation and improve water
      resource sustainability in mixed-land-use watersheds globally.

PMID- 28441602
TI  - Fluoride and iodine enrichment in groundwater of North China Plain: Evidences
      from speciation analysis and geochemical modeling.
AB  - To better understand the enrichment of fluoride and iodine in groundwater at
      North China Plain (NCP), speciation analysis and geochemical modeling were
      conducted to identify the key hydrochemical processes controlling their
      mobilization in groundwater system. Groundwater fluoride and iodine
      concentrations ranged from 0.18 to 5.59mg/L and from 1.51 to 1106MUg/L,
      respectively, and approximately 63% and 32.3% of groundwater fluoride and iodine
      were higher than the guidelines for drinking water (1.5mg/L and 150MUg/L). High
      fluoride concentration (>1.5mg/L) can be detected in groundwater from the flow
      through and discharge areas of NCP, and high iodine groundwater (>150MUg/L) is
      mainly scattered in the coastal area. Na-HCO3/Cl type water resulted from water
      rock interaction and seawater intrusion favors fluoride and iodine enrichment in
      groundwater. Speciation analysis results indicate that (1) fluoride complexes in
      groundwater are dominated by free fluoride, the negative charge of which favors
      fluoride enrichment in groundwater under basic conditions, and (2) iodide, iodate
      and organic iodine co-occur in groundwater at NCP with iodide as the dominant
      species. The geochemical modeling results indicate that groundwater fluoride is
      mainly associated with the saturation states of fluorite and calcite, as well as
      the adsorption equilibrium onto goethite and gibbsite, including the competitive
      adsorption between fluoride and carbonate. Groundwater iodine is mainly
      controlled by redox potential and pH condition of groundwater system. Reducing
      condition favors the mobilization and enrichment of groundwater iodide, which has
      the highest mobility among iodine species. Under reducing condition, reductive
      dissolution of iron (oxy)hydroxides is a potential geochemical process
      responsible for iodine release from sediment into groundwater. Under
      (sub)oxidizing condition, as groundwater pH over the 'point of zero charge' of
      iron (oxy)hydroxides, the lowering adsorption capacity of groundwater
      iodide/iodate on minerals leads to the release of sediment iodine into
      groundwater.

PMID- 28441603
TI  - Assessment of wastewater treatment facility compliance with decreasing ammonia
      discharge limits using a regression tree model.
AB  - A regression tree-based diagnostic approach is developed to evaluate factors
      affecting US wastewater treatment plant compliance with ammonia discharge permit
      limits using Discharge Monthly Report (DMR) data from a sample of 106 municipal
      treatment plants for the period of 2004-2008. Predictor variables used to fit the
      regression tree are selected using random forests, and consist of the previous
      month's effluent ammonia, influent flow rates and plant capacity utilization. The
      tree models are first used to evaluate compliance with existing ammonia discharge
      standards at each facility and then applied assuming more stringent discharge
      limits, under consideration in many states. The model predicts that the ability
      to meet both current and future limits depends primarily on the previous month's
      treatment performance. With more stringent discharge limits predicted ammonia
      concentration relative to the discharge limit, increases. In-sample validation
      shows that the regression trees can provide a median classification accuracy of
      >70%. The regression tree model is validated using ammonia discharge data from an
      operating wastewater treatment plant and is able to accurately predict the
      observed ammonia discharge category approximately 80% of the time, indicating
      that the regression tree model can be applied to predict compliance for
      individual treatment plants providing practical guidance for utilities and
      regulators with an interest in controlling ammonia discharges. The proposed
      methodology is also used to demonstrate how to delineate reliable sources of
      demand and supply in a point source-to-point source nutrient credit trading
      scheme, as well as how planners and decision makers can set reasonable discharge
      limits in future.

PMID- 28441604
TI  - Digital quantitative analysis of microRNA in single cell based on ligation
      depended polymerase colony (Polony).
AB  - The ability to dissect cell-to-cell variations of microRNA (miRNA) expression
      with single-cell resolution has become a powerful tool to investigate the
      regulatory function of miRNAs in biological processes and the pathogenesis of
      miRNA-related diseases. Herein, we have developed a novel scheme for digital
      detection of miRNA in single cell by using the ligation-depended DNA polymerase
      colony (polony). Firstly, two simply designed target-specific DNA probes were
      ligated by using individual miRNA as the template. Then the ligated DNA probe
      acted as polony template that was amplified by PCR process in the thin
      polyacrylamide hydrogel. Due to the covalent attachment of a PCR primer on
      polyacrylamide matrix and the retarding effect of the polyacrylamide hydrogel
      matrix itself, as the polony reaction proceeds, the PCR products diffused
      radially near individual template molecule to form a bacteria colony-like spots
      of DNA molecules. The spots can be counted after staining the polyacrylamide gel
      with SYBR Green I and imaging with a microarray scanner. Our polony-based method
      is sensitive enough to detect 60 copies of miRNA molecules. Meanwhile, the new
      strategy has the capability of distinguishing singe-base difference. Due to its
      high sensitivity and specificity, the proposed method has been successfully
      applied to analysis of the expression profiling of miRNA in single cell.

PMID- 28441606
TI  - Growth inhibition and antibiofilm potential of Ag nanoparticles coated with
      lectin, an arthropod immune molecule.
AB  - Lectins from the haemolymph of arthropods, including crustaceans, are molecules
      potentially involved in the immune recognition and phagocytosis. Here, lectin was
      purified from the haemolymph of blue swimmer crab Portunus pelagicus, using
      mannose-coupled sepharose CL-4B affinity column chromatography. In SDS-PAGE
      analysis, lectin showed a molecular mass of approximately 155kDa. The synthesis
      of lectin-coated silver nanoparticles (lectin-coated AgNPs) was confirmed by UV
      Vis spectroscopy, XRD, FTIR, SEM, TEM, SAED, and EDX analysis. TEM analysis
      revealed that lectin-coated AgNPs were spherical in shape with size of 30-57nm.
      Their antibacterial activity against human pathogenic Gram negative and Gram
      positive bacteria was determined by agar well diffusion method. Lectin-coated
      AgNPs showed significant antimicrobial activity when compared to lectin and
      silver nitrate tested alone. The antibiofilm properties of lectin-coated AgNPs
      were also investigated on human pathogenic Gram-negative Proteus vulgaris,
      Pseudomonas aeruginosa and Gram-positive Enterococcus faecalis and Bacillus
      pumilus. Lectin-coated AgNPs showed antibiofilm activity on the bacteria as well
      as on Candida albicans. Lectin-coated AgNPs reduced the biofilm architecture
      interfering with cell adhesion and polysaccharide matrix. This was additionally
      confirmed by exopolysaccharide (EPS) quantification index revealing the trouble
      in the structural reliability of biofilm by decrease in EPS and bacterial
      adhesion to hydrocarbons.

PMID- 28441605
TI  - Biological effects and medical applications of infrared radiation.
AB  - Infrared (IR) radiation is electromagnetic radiation with wavelengths between
      760nm and 100,000nm. Low-level light therapy (LLLT) or photobiomodulation (PBM)
      therapy generally employs light at red and near-infrared wavelengths (600-100nm)
      to modulate biological activity. Many factors, conditions, and parameters
      influence the therapeutic effects of IR, including fluence, irradiance, treatment
      timing and repetition, pulsing, and wavelength. Increasing evidence suggests that
      IR can carry out photostimulation and photobiomodulation effects particularly
      benefiting neural stimulation, wound healing, and cancer treatment. Nerve cells
      respond particularly well to IR, which has been proposed for a range of
      neurostimulation and neuromodulation applications, and recent progress in neural
      stimulation and regeneration are discussed in this review. The applications of IR
      therapy have moved on rapidly in recent years. For example, IR therapy has been
      developed that does not actually require an external power source, such as IR
      emitting materials, and garments that can be powered by body heat alone. Another
      area of interest is the possible involvement of solar IR radiation in photoaging
      or photorejuvenation as opposites sides of the coin, and whether sunscreens
      should protect against solar IR? A better understanding of new developments and
      biological implications of IR could help us to improve therapeutic effectiveness
      or develop new methods of PBM using IR wavelengths.

PMID- 28441607
TI  - Toxicity assessment of ZnO-decorated Au nanoparticles in the Mediterranean clam
      Ruditapes decussatus.
AB  - The synthesis of hybrid nanomaterials has greatly increased in recent years due
      to their special physical and chemical properties. However, information regarding
      the environmental toxicity associated with these chemicals is limited, in
      particular in the aquatic environment. In the present study, an experiment was
      performed in which the marine bivalve (Ruditapes decussatus) was exposed for
      14days to 2 concentrations of zinc oxide-decorated Au nanoparticles (Au-ZnONPs:
      Au-ZnONP50=50MUg/L; Au-ZnONP100=100MUg/L). The stability and resistance of Au
      ZnONPs in the natural seawater were assessed by combining transmission electron
      microscopy and dynamic light scattering. Inductively coupled plasma-atomic
      emission spectroscopy revealed uptake of these nanoparticles within clams and
      their ability to induce metallic deregulation. The results obtained indicate that
      Au-ZnONPs induce biochemical and histological alterations within either the
      digestive gland or gill tissues at high concentration. This was deduced from the
      significant increase in H2O2 level, superoxide dismutase and catalase activities
      and malondialdehyde content. Furthermore, the toxicity of Au-ZnO nanoparticles
      was linked with the increase of intracellular iron and calcium levels in both
      tissues. Histological alterations in gill and digestive gland were more
      pronounced with Au-ZnONP100 and this is likely related to oxidative mechanisms.
      Gill and digestive gland are differentially sensitive to Au-ZnONPs if the
      exposure concentration is higher than 50MUg/L. In conclusion, the parameters
      considered here could constitute reliable biomarkers for evaluation of hybrid
      nanoparticles toxicity in environmental model organisms. In addition, based on
      the results obtained, gill and digestive gland of R. decussatus could be proposed
      as models to detect harmful effects of hybrid nanoparticles.

PMID- 28441608
TI  - Phylogenetic signals in detoxification pathways in Cyprinid and Centrarchid
      species in relation to sensitivity to environmental pollutants.
AB  - Observations in a previous study on biomarker responses in fish collected from
      urban creeks in Greenville, SC, indicated that there might be considerable
      differences in the expression of biotransformation enzymes in chub and sunfish
      species. To further investigate these species differences a dosing experiment was
      performed in which bluehead and creek chub (Nocomis leptocephalus and Semotilus
      atromaculatus), and redbreast sunfish, pumpkinseed, and bluegill (Lepomis
      auritus, L. gibbosus, and L. macrochirus) were injected with benzo[a]pyrene (BaP)
      as a model compound for common pollutants in urban creeks. Fish were injected
      with BaP doses of 0, 25 and 50mg/kg, and after 3days BaP metabolites in bile, and
      enzymatic activities of cytochrome P450-1A (CYP1A), UDP-glucuronosyltransferase
      (UGT) and glutathione S-transferase (GST) were measured. CYP1A activity was
      significantly increased after BaP dosing in both species groups, but chubs had
      significantly lower levels than were observed in the dosed sunfish. The UGT
      activity in unexposed animals was comparable in both species groups, and
      significantly increased in both groups as a result of BaP dosage. Finally, GST
      activity was significantly higher in chubs, but did not change in either species
      group as a result of BaP exposure. There were no significant differences between
      species within each species group, and the results confirmed that unexposed chubs
      have much lower CYP1A activity, but a much higher GST activity than unexposed
      sunfish. The metabolized BaP was excreted in both species groups, but at the time
      of sampling there were no differences in the amount of BaP metabolites in the
      bile of dosed animals. The differences in baseline enzyme activity and induction
      capacity between both species groups are an example of phylogenetically
      determined differences between fish families, and may explain why chubs are in
      general more sensitive to exposure to environmental pollutants than sunfish. This
      conclusion was corroborated by the observation that the highest BaP dose of
      50mg/kg was close to the apparent LC50 for chub, while no mortality was observed
      in the sunfish at this dose.

PMID- 28441609
TI  - Dechlorane Plus induces oxidative stress and decreases cyclooxygenase activity in
      the blue mussel.
AB  - Dechlorane Plus (DP) is a chlorinated flame retardant used mainly in electrical
      wire and cable coating, computer connectors, and plastic roofing materials.
      Concentrations of DP (syn and anti isomers) are increasingly being reported in
      aquatic ecosystems worldwide. However, there is exceedingly little information on
      the exposure-related toxicity of DP in aquatic organisms, especially in bivalves.
      The objective of this study was to investigate the in vivo and in vitro effects
      of DP exposure on histopathology, lipid peroxidation (LPO) levels, cyclooxygenase
      (COX) activity, phagocytosis capacity and efficiency, and DNA strand breakage in
      the blue mussel (Mytilus edulis) following a 29days exposure (0.001, 0.01, 0.1
      and 1.0MUg DP/L). Blue mussels accumulated DP in muscle and digestive gland in a
      dose-dependent manner. LPO levels in gills were found to increase by 82% and 67%
      at the 0.01 and 1.0MUg DP/L doses, respectively, while COX activity in gills
      decreased by 44% at the 1MUg/L dose. No histopathological lesion was found in
      gonads following DP exposure. Moreover, no change in hemocyte DNA strand
      breakage, phagocytosis rate, and viability was observed following DP exposure.
      Present study showed that toxicity of DP may occur primarily via oxidative stress
      in the blue mussel and potentially other bivalves, and that gills represent the
      most responsive tissue to this exposure.

PMID- 28441610
TI  - Total esterase measurement in saliva of pigs: Validation of an automated assay,
      characterization and changes in stress and disease conditions.
AB  - An automated spectrophotometric method for total esterase activity (TEA)
      measurement in porcine saliva has been developed and validated, using 4
      nitrophenyl acetate (4-NA) as substrate. The method was precise and accurate,
      with low limit of detection, and was able to measure samples with TEA activities
      up to 400IU/L without any dilution. In addition, the different enzymes
      contributing to TEA were characterized, being identified carbonic anhydrase VI
      (CA-VI), lipase, cholinesterase (ChE) and cholesterol esterase (CEL). TEA
      significantly increased (1.49-fold, P<0.01) in healthy pigs just after applying
      an acute stress stimulus consisting of nasal restraint, being lipase and
      cholinesterase the main responsible of this increase. TEA was significantly
      increased (1.83-fold, P<0.001) in a group of pigs with lameness; in this case, in
      addition to lipase and ChE, CA-VI also increased. The results found in this
      report indicate that TEA can be easily measured in porcine saliva with an
      accurate and highly reproducible automated method. Salivary TEA is mainly due to
      the activity of four enzymes: CA-VI, lipase, ChE and CEL, and these enzymes can
      change in a different way in situations of stress or disease.

PMID- 28441612
TI  - Mass loading and removal of benzotriazoles, benzothiazoles, benzophenones, and
      bisphenols in Indian sewage treatment plants.
AB  - Little is known about the occurrence of emerging environmental contaminants, such
      as benzotriazoles (BTRs), benzothiazoles (BTHs), benzophenones (BzPs), and
      bisphenol analogues (BPs) in India. In this study, we determined the occurrence
      and removal of BTRs, BTHs, BzPs, and BPs in five Indian sewage treatment plants
      (STPs). The respective measured mean concentrations (N = 5) in influents and
      effluents were 370 and 57.4 ng L-1 for BTRs, 50800 and 20200 ng L-1 for BTHs, 351
      and 163 ng L-1 for BzPs, and 98.0 and 9.6 ng L-1 for BPs. Among the target
      chemicals analyzed, BTHs were found at elevated levels, and the measured levels
      were some of the highest ever reported in the literature. The mean concentrations
      (N = 5) of BTRs, BTHs, BzPs, and BPs in sludge were 44.2, 51200, 124, and 200 ng
      g-1 dry wt, respectively. The removal efficiencies for BTRs, BTHs, BzPs, and BPs
      ranged as follows: 54.2-85.6%, 23.4-85.0%, 51.8-71%, and 76.0-97.0%,
      respectively, and were comparable to those reported for other countries. Elevated
      concentrations of BTHs in Indian STPs can be related to consumption of these
      chemicals in a wide range of products including paper, textile and rubber
      materials.

PMID- 28441611
TI  - Genotoxic effect of Pb and Cd on in vitro cultures of Sphagnum palustre: An
      evaluation by ISSR markers.
AB  - In the present work, the genotoxic effect of cadmium and lead supplied in a
      laboratory trial, was investigated for the first time in the moss Sphagnum
      palustre, by ISSR molecular markers. A total of 169 reproducible bands were
      obtained with 12 primers, ten of which gave polymorphisms (i.e.,
      appearance/disappearance of bands), indicating a clear genotoxic effect induced
      by the metals. Both metals induced a decrease of the genome template stability in
      a dose dependent manner. At concentration >10-5 Cd also induced a general toxic
      effect in S. palustre, leading to chlorophyll degradation and moss death.
      Moreover, we followed the fate of supplied heavy metals into the moss tissue by
      SEM-EDX to see if they entered the cells. SEM-EDX observations on moss cultures
      treated with equimolar concentrations of the two metals showed that most Pb
      precipitated in form of particles on moss surface, while Cd did not aggregate in
      particles and was not found on moss surface. In light of these findings, we
      concluded that probably Pb induced a genotoxic effect at lower intracellular
      concentrations than Cd.

PMID- 28441613
TI  - Atmospheric degradation of 2-chloroethyl vinyl ether, allyl ether and allyl ethyl
      ether: Kinetics with OH radicals and UV photochemistry.
AB  - Unsaturated ethers are oxygenated volatile organic compounds (OVOCs) emitted by
      anthropogenic sources. Potential removal processes in the troposphere are
      initiated by hydroxyl (OH) radicals and photochemistry. In this work, we report
      for the first time the rate coefficients of the gas-phase reaction with OH
      radicals (kOH) of 2-chloroethyl vinyl ether (2ClEVE), allyl ether (AE), and allyl
      ethyl ether (AEE) as a function of temperature in the 263-358 K range, measured
      by the pulsed laser photolysis-laser induced fluorescence technique. No pressure
      dependence of kOH was observed in the 50-500 Torr range in He as bath gas, while
      a slightly negative T-dependence was observed. The temperature dependent
      expressions for the rate coefficients determined in this work are: The estimated
      atmospheric lifetimes (tauOH) assuming kOH at 288 K were 3, 2, and 4 h for
      2ClEVE, AE and AEE, respectively. The kinetic results are discussed in terms of
      the chemical structure of the unsaturated ethers by comparison with similar
      compounds. We also report ultraviolet (UV) and infrared (IR) absorption cross
      sections (sigmalambda and sigma(nu~), respectively). We estimate the photolysis
      rate coefficients in the solar UV actinic region to be less than 10-7 s-1,
      implying that these compounds are not removed from the atmosphere by this
      process. In addition, from sigma(nu~) and tauOH, the global warming potential of
      each unsaturated ether was calculated to be almost zero. A discussion on the
      atmospheric implications of the titled compounds is presented.

PMID- 28441614
TI  - Learning from an analysis of closed malpractice litigation involving myocardial
      infarction.
AB  - OBJECTIVE: To examine the epidemiologic data, identify the pattern of dispute,
      and determine clinical litigious errors by analyzing closed malpractice claims
      involving myocardial infarction (MI) in Taiwanese courts. METHODS: A
      retrospective descriptive study was performed to analyze the verdicts pertaining
      to MI from the population-based database of the Taiwan judicial system between
      2002 and 2013. The results of adjudication, involved specialists, primary dispute
      leading to lawsuits, and litigious errors were recorded. RESULTS: A total of 36
      closed malpractice claims involving MI were included. The mean interval between
      the incident and litigation closure was 65.5 +/- 28.3 months. Nearly 20% of the
      cases were judged against clinicians and the mean payment was $100639 +/- 49617,
      while the mean imprisonment sentence was 4.3 +/- 1.8 months. Cardiologists and
      emergency physicians were involved in 56.3% of cases, but won 92.6% of lawsuits,
      while other specialists lost nearly 25% of lawsuits. The most common dispute was
      misdiagnosis (38.9%), but this dispute had the lowest percentage of loss (7.1%).
      Disputes regarding delayed diagnosis were judged against the defendants in 50% of
      claims. Clinicians lost the lawsuit in the following conditions: 1) misdiagnosis
      of MI in patients with typical chest pain and known coronary artery risk factors;
      2) failure to perform thoughtful evaluation and series investigations in patients
      suspicious of ischemic heart disease; 3) failure to perform indicated treatment
      to avoid disease progression. CONCLUSIONS: Medical practitioners should keep a
      high index of MI suspicion, especially if the diagnosis and treatment of MI are
      beyond their daily practice. Prudent patient reevaluation, serial ECG and cardiac
      enzyme testing, and early consultation are suggested to reduce malpractice
      liability.

PMID- 28441615
TI  - Near-infrared light stimuli-responsive synergistic therapy nanoplatforms based on
      the coordination of tellurium-containing block polymer and cisplatin for cancer
      treatment.
AB  - Cisplatin (CDDP) has received worldwide approval for clinical use in the past
      decades. However, its development in cancer chemotherapy was overshadowed by
      severe side effects and drug resistance. Herein, we developed a CDDP drug
      delivery system with high encapsulation efficiency and near-infrared light
      stimuli-responsive drug release properties based on the coordination of novel
      tellurium-containing block polymer (PEG-PUTe-PEG) and CDDP. The nanocarriers made
      from PEG-PUTe-PEG were loaded with CDDP and indocyanine green (ICG)
      simultaneously. The coordination chemistry between CDDP and tellurium guaranteed
      the nanocarrier a high stability in plasma and prolonged circulation time in vivo
      by reducing possible penetration of water molecule into the nanoparticles. Under
      the stimuli of a near-infrared laser, an amount of ROS can be generated by
      irradiation of ICG. The tellurium is easily oxidized by ROS because of the low
      electronegativity of tellurium. The CDDP could be rapidly released from the
      nanocarriers along with the oxidation of the tellurium at the tumor sites as the
      oxidized tellurium will weaken the coordination interaction with CDDP. In
      addition, the encapsulated ICG played a synergistic antitumor effect through
      photothermal effect with mild laser irradiation. The integrated strategy achieved
      higher antitumor efficacy and showed minimal side effects compared with the CDDP
      alone.

PMID- 28441616
TI  - Core-shell hierarchical mesostructured silica nanoparticles for gene/chemo
      synergetic stepwise therapy of multidrug-resistant cancer.
AB  - The design and synthesis of hierarchically nanoporous structures for the co
      encapsulation and sequential releases of different cargos are still great
      challenges in biomedical applications. In this work, we report on the elaborate
      design and controlled synthesis of a unique core-shell hierarchical mesoporous
      silica/organosilica nanosystem, in which there are large and small mesopores
      separately present in the shell and core, facilitating the independent
      encapsulations of large (siRNA) and small (doxorubicin) molecules, respectively.
      Importantly, the framework of the organosilica shell is molecularly hybridized
      with disulfide bonds, which enables the unique responsiveness to the reductive
      tumor microenvironment for the controlled releasing of loaded gene molecules,
      followed by the subsequent doxorubicin release. The first released large siRNA
      molecules from the organosilica shell down-regulated the expression of P-gp in
      the cell membrane and reversed the MDR of cancer cells, thus enhancing the
      antitumor effect of subsequently released small DOX molecules from the silica
      core, and in such a synergetic way the MDR tumor growth can be efficiently
      inhibited. This work shows the significant advantages compared to the traditional
      small-mesoporous or large-mesoporous nanosystems for drug co-delivery.

PMID- 28441617
TI  - The MAGIC survey in hormone receptor positive (HR+), HER2-negative (HER2-) breast
      cancer: When might multigene assays be of value?
AB  - BACKGROUND: A modest proportion of patients with early stage hormone receptor
      positive (HR+), HER2-negative (HER2-) breast cancer benefit from adjuvant
      chemotherapy. Traditionally, treatment recommendations are based on
      clinical/pathologic criteria that are not predictive of chemotherapy benefit.
      Multigene assays provide prognostic and predictive information that can help to
      make more informed treatment decisions. The MAGIC survey evaluated international
      differences in treatment recommendations, how traditional parameters are used for
      making treatment choices, and for which patients treating physicians feel most
      uncertain about their decisions. METHODS: The MAGIC survey captured respondents'
      demographics, practice patterns, relevance of traditional parameters for
      treatment decisions, and use of or interest in using multigene assays. Using this
      information, a predictive model was created to simulate treatment recommendations
      for 672 patient profiles. RESULTS: The survey was completed by 911 respondents
      (879 clinicians, 32 pathologists) from 52 countries. Chemo-endocrine therapy was
      recommended more often than endocrine therapy alone, but there was substantial
      heterogeneity in treatment recommendations in 52% of the patient profiles;
      approximately every fourth physician provided a different treatment
      recommendation. The majority of physicians indicated they wanted to use multigene
      assays clinically. Lack of reimbursement/availability were the main reasons for
      non-usage. CONCLUSIONS: The survey reveals substantial heterogeneity in treatment
      recommendations. Physicians have uncertainty in treatment recommendations in a
      high proportion of patients with intermediate risk features using traditional
      parameters. In HR+, HER2- patients with early disease the findings highlight the
      need for additional markers that are both prognostic and predictive of
      chemotherapy benefit that may support more-informed treatment decisions.

PMID- 28441619
TI  - The influence of attention biases and adult attachment style on treatment outcome
      for adults with social anxiety disorder.
AB  - BACKGROUND: Attention biases figure prominently in CBT models of social anxiety
      and are thought to maintain symptoms of social anxiety disorder (SAD). Studies
      have shown that individual differences in pre-treatment attention biases predict
      cognitive behavioural therapy (CBT) outcome. However, these findings have been
      inconsistent as to whether vigilance towards threat predicts better or poorer
      treatment outcome. Adult attachment style is an individual characteristic that
      may influence the relationship between attention bias and SAD. This study
      investigates the relationship between attention biases and CBT treatment outcome
      for SAD. Furthermore, we examined the influence of adult attachment style on this
      relationship. METHOD: Participants with a primary diagnosis of SAD completed a
      passive viewing (measuring vigilance towards threat) and a novel difficulty to
      disengage (measuring difficulty to disengage attention) eye-tracking task prior
      to attending 12 CBT group sessions targeting SAD. Symptom severity was measured
      at pre- and post-treatment. Regression analyses were conducted on a sample of 50
      participants. RESULTS: Greater vigilance for threat than avoidance of threat at
      pre-treatment predicted poorer treatment outcomes. Greater difficulty disengaging
      from happy faces, compared to neutral faces, predicted poorer treatment outcomes.
      Attachment style did not moderate these relationships. LIMITATIONS: The
      associations between attention biases and specific components of CBT treatment
      were not examined. The novel findings regarding difficulty to disengage attention
      require replication. CONCLUSIONS: The findings have implications for the
      theoretical models of SAD and for the treatment of SAD.

PMID- 28441618
TI  - Motivation deficits and use of alcohol and illicit drugs among individuals with
      schizophrenia.
AB  - This study examined the impact of substance use on intrinsic motivation and
      evaluated the association between intrinsic motivation and substance use recovery
      among individuals with schizophrenia. Alcohol and illicit drug use and intrinsic
      motivation were evaluated at baseline and 6-months for 1434 individuals with
      schizophrenia from the Clinical Antipsychotic Trials of Intervention
      Effectiveness (CATIE) using self-rated substance use assessments and a derived
      motivation measure from the Heinrichs-Carpenter Quality of Life Scale. Results
      revealed patients had moderate motivation deficits overall and a considerable
      number were using alcohol or illicit drugs at baseline (n=576; 40.2%). Regression
      models at baseline showed patients with low levels of motivation had higher odds
      of substance use and those who were using substances had greater motivation
      deficits. At 6-months, substance using patients continued to demonstrate greater
      motivation deficits; however, those with high levels of motivation exhibited a
      greater reduction in their use of substances. Findings remained significant after
      adjusting for clinical confounds and were consistent across any substance,
      alcohol, and cannabis use. Our results emphasize concerns about substance use
      compounding motivation deficits in schizophrenia, and suggest that disentangling
      the motivation-substance use relationship in schizophrenia may facilitate efforts
      aimed at ameliorating these challenges and improving outcomes.

PMID- 28441621
TI  - Prion-like transmission of pathogenic protein aggregates in genetic models of
      neurodegenerative disease.
AB  - A key pathological hallmark of most neurodegenerative diseases is the misfolding
      of a particular protein, leading to deposition of toxic protein aggregates in
      brain tissue. Recent data provide compelling evidence that pathogenic protein
      aggregates have prion-like properties-they self-replicate by templated misfolding
      of monomeric proteins and spread between individual cells. Studies in genetic
      model organisms have expanded our understanding of how prion-like pathogenic
      aggregates propagate in vivo, revealing potential roles for spreading along
      neural networks and key cellular processes in both neurons and glial cells. These
      findings and future studies in genetic models will help guide the development of
      novel therapeutic strategies that directly target the molecular mechanisms
      underlying these devastating diseases.

PMID- 28441620
TI  - Cognitive behavioral therapy is effective in misophonia: An open trial.
AB  - BACKGROUND: Misophonia is a psychiatric disorder in which ordinary human sounds
      like smacking or chewing provoke intense anger and disgust. Despite the high
      burden of this condition, to date there is no evidence-based treatment available.
      In this study we evaluated the efficacy of cognitive behavioral therapy (CBT) and
      investigated whether clinical or demographic characteristics predicted treatment
      response. METHODS: Ninety patients with misophonia received eight bi-weekly group
      CBT sessions. Treatment response was defined as a Clinical Global Impression -
      Improvement Scale (CGI-I) score at endpoint of 1 or 2 (very much or much
      improved) and a 30% or greater reduction on the Amsterdam Misophonia Scale (A
      MISO-S), a measure of the severity of misophonia symptoms. RESULTS: Following
      treatment 48% (N=42) of the patients showed a significant reduction of misophonia
      symptoms. Severity of misophonia and the presence of disgust were positive
      predictors of treatment response. LIMITATIONS: The A-MISO-S is not a validated
      scale. Furthermore, this was an open-label study with a waiting list control
      condition. CONCLUSIONS: This is the first treatment study for misophonia. Our
      results suggest that CBT is effective in half of the patients.

PMID- 28441622
TI  - Social anxiety and disordered eating: The influence of stress reactivity and self
      esteem.
AB  - While previous research indicates a strong link between social anxiety and
      disordered eating, more research is needed in order to understand the mechanisms
      that underlie this relationship. Given that stress is often implicated in
      disordered eating, it was hypothesised that ones reaction to stress (i.e. stress
      reactivity) would mediate the relationship between social anxiety and disordered
      eating. Similarly, given that low self-esteem is commonly reported in both those
      with social anxiety and eating disorders, it was hypothesised that self-esteem
      would also mediate the relationship between social anxiety and disordered eating.
      In order to test this, an online survey measuring social anxiety, disordered
      eating, stress reactivity and self-esteem, was administered to 282 participants
      in the community, aged between 18 and 35years. Results showed that self-esteem
      and a reactivity to stress during social conflict - but not during negative
      social evaluations - partially mediated the relationship between social anxiety
      and disordered eating. These findings demonstrate that low self-esteem and
      interpersonal conflict are powerful mechanisms that can maintain eating disorder
      psychopathology in those who are socially anxious. This highlights the importance
      of ensuring that these mechanisms are sufficiently addressed in eating disorder
      prevention and treatment programs.

PMID- 28441623
TI  - Identification of a Macrobrachium nipponense C-type lectin with a close
      evolutionary relationship to vertebrate lectins.
AB  - C-type lectins (CTLs) are involved in the innate immune defense of vertebrates
      and invertebrates against invading pathogens. This study cloned and characterized
      a novel C-type lectin (MnCTL) of the oriental river prawn, Macrobrachium
      nipponense. The cloned MnCTL cDNA encompasses an open reading frame of 774
      nucleotides and encodes polypeptides of 257 residues. The deduced MnCTL protein
      contains a single carbohydrate recognition domain (CRD) with an EPN (Glu-Pro-Asn)
      motif in calcium-binding site 2. Phylogenetic analysis indicated that MnCTL has a
      closer evolutionary relationship with vertebrate lectins than with invertebrate
      lectins. Tissue expression analysis showed that high levels of MnCTL are
      ubiquitously distributed in the gills and stomach of M. nipponense. Quantitative
      real-time RT-PCR (qRT-PCR) analysis showed that MnCTL expression was up-regulated
      by bacteria or white spot syndrome virus (WSSV) challenge. Knock-down of the
      MnCTL gene in WSSV-challenged prawns significantly decreased MnALF1 and MnALF2
      transcript levels. The recombinant MnCRD (rMnCRD) agglutinated both Gram-positive
      (Staphylococcus aureus) and Gram-negative bacteria (Vibrio parahaemolyticus) in
      the presence of calcium. Furthermore, rMnCRD could bind to all the tested
      bacteria with different activities. The sugar-binding assay showed that rMnCRD
      was able to bind lipopolysaccharide and peptidoglycan in a concentration
      dependent manner. In addition, rMnCRD could accelerate bacterial clearance. On
      the contrary, MnCTL silencing by dsRNA interference could weaken the bacterial
      clearance ability. All these findings implicated MnCTL were involved in the
      antiviral and antibacterial innate immunity of M. nipponense.

PMID- 28441624
TI  - Various soil amendments and environmental wastes affect the (im)mobilization and
      phytoavailability of potentially toxic elements in a sewage effluent irrigated
      sandy soil.
AB  - Contamination of long-term sewage effluent irrigated soils by potentially toxic
      elements (PTEs) is a serious concern due to its high environmental and health
      risk. Our scientific hypothesis is that soil amendments can cause contradictory
      effects on the element mobilization and phytoavailability depending on the type
      of element and amendment. Therefore, we aimed to assess the impact of the
      application (1%) of several low cost amendments and environmental wastes on the
      (im)mobilization, availability, and uptake of Al, Cd, Cr, Cu, Fe, Mn, Ni, and Zn
      by sorghum (Sorghum bicolor) in a long term sewage effluent irrigated sandy soils
      collected from Egypt. The used materials include activated charcoal (AC),
      potassium humate (KH), phosphate rock (PR), phosphogypsum (PG), triple
      superphosphate (TSP), phosphoric acid (PA), sulfur (S), sugar beet factory lime
      (SBFL), cement bypass kiln dust (CBD), egg shell (ES), bone mill (BM), brick
      factory residual (BFR), ceramic powder (CP), and drinking water treatment
      residual (WTR). The mobilization and availability of the elements in the soil
      were extracted using NH4NO3 and ammonium bicarbonate- diethylene triamine penta
      acetic acid (AB-DTPA), respectively. The above-ground biomass samples were
      analyzed for the elements studied. The results confirmed our hypothesis and
      concluded that although some amendments like S, PA, and TSP can be used for
      reducing the plant uptake of Al, Cr, and Fe, they might be used with KH for
      enhancing the phytoextraction of Cd, Cu, Mn, and Ni. Moreover, several wastes
      such as BFR and WTR might be used for enhancing the phytoextraction of Al, Cd,
      Cr, Cu, Fe, and Ni and reducing the uptake of Mn from the studied soil. Although
      SBFL decreased the plant uptake of Al, Fe, Mn, and Zn, it's increased the plant
      uptake of Cd, Cu, and Ni. Therefore, the amendments which reduce the plant uptake
      of an element might be suitable candidates for its immobilization, while the
      amendments which increase the plant uptake of an element might be used for
      enhancing its phytoextraction when using bioenergy crops like sorghum in similar
      contaminated sandy soils. The studied materials offered the potential for
      effective and low cost media for the treatment of PTEs contaminated sewage
      effluent irrigated sandy soils. These results should be verified in a field
      study.

PMID- 28441625
TI  - Influence of co-existed tetrabromobisphenol A (TBBPA) and hexavalent chromium on
      the cellular characteristics of Pycnoporus sanguineus during their removal and
      reduction.
AB  - Simultaneous TBBPA removal and Cr(VI) reduction by Pycnoporus sanguineus together
      with the effect of these co-existed pollutants on the fungal cellular
      characteristics were investigated in this study, aiming at illuminating the
      mechanism involved in the interactions between contaminants and microbial cells.
      The results revealed that Cr(VI) reduction and TBBPA removal declined from 92.5%,
      75.4-30.6%, 44.8% when Cr(VI) concentration increased from 5 to 40mg/L,
      respectively. The removal efficiencies for Cr(VI) and TBBPA reached 61.4% and 94%
      separately under the optimum concentration of TBBPA at 10mg/L. Subsequent
      analyses indicated that the negative effect of Cr(VI) of high concentrations on
      Cr(VI) reduction and TBBPA removal was mainly attributed to the inhibition of
      fungal growth, intracellular proteins synthesis, cell viability and ATP enzyme
      activity. Compared with the moderate impact of TBBPA, the cell membrane of P.
      sanguineus was impaired severely and the surface morphology and intracellular
      structure changed dramatically in the presence of high concentration of Cr(VI)
      (above 10mg/L). This study also suggested that high level of TBBPA (15 and
      20mg/L) promoted the synthesis of intracellular proteins and improved ATP enzyme
      activity within the first 48h of the reaction for enhancing the transportation
      and transformation of TBBPA.

PMID- 28441626
TI  - Myobolites: muscle-derived metabolites with paracrine and systemic effects.
AB  - Intracellular metabolism in skeletal muscle has been studied for more than a
      century and is the stuff of textbooks. In contrast, the extracellular secretion
      of metabolites by muscle cells, and their effects on non-muscle cells near or
      far, has been investigated much less extensively. Here, we describe a number of
      cases in which striated muscle secretes a metabolite that elicits complex
      responses in other cells or tissues, with involvements in normal physiology as
      well as obesity, type II diabetes, and cardiac remodeling. We focus on two
      recently identified secreted catabolic products of branched chain amino acid
      breakdown, beta-aminoisobutyric acid and 3-hydroxyisobutyrate, and discuss common
      themes of inter-cellular signaling pathways driven by secreted metabolites.

PMID- 28441627
TI  - Effect of in vitro drought stress on phenolic acids, flavonols, saponins, and
      antioxidant activity in Agave salmiana.
AB  - This work evaluated the effect of in vitro drought stress on morphological
      characteristics, phenolic compounds, flavonols, saponin content, and antioxidant
      activity in plantlets of Agave salmiana. Drought stress was induced with
      polyethylene glycol (PEG) at 0, 10, 20 and 30% w/v in Murashige and Skoog solid
      medium. The determination of specific flavonols and saponins was achieved via
      HPLC-DAD and HPLC-ELSD, respectively. Compared with the control, plants grown in
      30% PEG showed a change in the width of the leaves and a different color, showing
      less clarity and more darkening (L = 21.18, b = 14.27) and also had the lowest
      flavonol content, but the highest total saponin content (tigogenin glycoside, 163
      mg of protodioscin equivalents/g dw) and the highest antioxidant activity. Total
      phenolic compounds did not significantly differ between treatments. Agave
      salmiana plants cultured in vitro increased their saponin content and antioxidant
      activity in response to drought stress induced via PEG.

PMID- 28441628
TI  - Potassium deficiency affects the carbon-nitrogen balance in cotton leaves.
AB  - Potassium (K) plays important roles in the metabolism of carbon (C) and nitrogen
      (N), but studies of K deficiency affecting C-N balance are lacking. This study
      explored the influence of K deficiency on C-N interaction in cotton leaves by
      conducting a field experiment with cotton cultivar DP0912 under two K rates (K0:
      0 kg K2O ha-1 and K67: 67 kg K2O ha-1) and a controlled environment experiment
      with K-deficient solution (K1: 0 mM K+) and K-sufficient solution (K2: 6 mM K+).
      The results showed that leaf K content, leaf number, leaf area, boll number,
      reproductive dry weight and total dry weight were significant lower under K
      deficiency (K0 or K1). Lower total chlorophyll content and Chl a/b ratio, and
      decreased Pn along with lower Gs and higher Ci were measured under K deficiency,
      suggesting that the decrease in Pn was resulted from non-stomatal limitation.
      Leaf glucose, fructose, sucrose and starch contents were higher under K
      deficiency, because lower sucrose export was detected in phloem. Although leaf
      nitrate and ammonium contents significantly decreased, free amino acid content
      was increased by 40-63% under K deficiency, since lower amino acid export was
      also measured in phloem. K deficiency also induced lower soluble protein content
      in leaves. Leaf ATP level was significantly increased under K deficiency,
      indicating ATP utilization was lower, so that less energy was supplied to C and N
      metabolism. The ratio of soluble sugar to free amino acid and the C/N ratio
      markedly increased under K deficiency, and one reason was that the phloem export
      reduced more prominent for sucrose (54.6-78.0%) than amino acid (36.7-85.4%)
      under K deficiency. In addition, lower phosphoenolpyruvate carboxylase activity
      limited malate and citrate biosynthesis under K deficiency, causing a decrease of
      C flux into the amino acids, which was not beneficial for maintaining C-N
      balance. Sucrose phosphate synthase and nitrate reductase activities were lower
      under K deficiency, which would limit sucrose biosynthesis and nitrate
      assimilation. This was another factor altering soluble sugar to free amino acid
      ratio and C/N ratio in the K-deficient leaves.

PMID- 28441630
TI  - Winter to summer change in vitamin D status reduces systemic inflammation and
      bioenergetic activity of human peripheral blood mononuclear cells.
AB  - BACKGROUND: Vitamin D status [25(OH)D] has recently been reported to be
      associated with altered cellular bioenergetic profiles of peripheral blood
      mononuclear cells (PBMCs). No study has tracked the seasonal variation of 25(OH)D
      and its putative influence on whole body energy metabolism, cellular bioenergetic
      profiles, inflammatory markers and clinical chemistry. MATERIAL AND METHODS:
      Whole body energy metabolism and substrate utilisation were measured by indirect
      calorimetry. PBMCs obtained from the same subjects were isolated from whole
      blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress
      test and glycolysis stress test) was performed using the Seahorse XFe96 flux
      analyser. 25(OH)D was assessed using the Architect immunoassay method. RESULTS:
      25(OH)D increased by a median (IQR) of 14.40 (20.13)nmol/L (p<0.001) from winter
      to summer and was accompanied by significant improvements in indices of insulin
      sensitivity, McAuley's index (p=0.019) and quantitative insulin sensitivity check
      index (p=0.028). PBMC mitochondrial parameters basal respiration, non
      mitochondrial respiration, ATP production, proton leak, and maximal respiration
      decreased in summer compared to winter. Similarly, PBMC glycolytic parameters
      glycolytic activity, glucose response, and glycolytic capacity were all reduced
      in summer compared to winter. There was also a trend for absolute resting
      metabolic rate (RMR) to decrease (p=0.066). Markers of systemic inflammation MCP
      1, IL-6, IL-8, IL-10, and IL-12p70 decreased significantly in summer compared to
      winter. Participants who entered winter with a low 25(OH)D (<50nmol/L), had the
      greatest alteration in bioenergetic parameters in summer, relative to those with
      winter 25(OH)D concentrations of 50-75nmol/L or >75nmol/L. The absolute change in
      25(OH)D was not associated with altered bioenergetics. CONCLUSION: Seasonal
      improvements in 25(OH)D was associated with reduced systemic inflammation, PBMC
      bioenergetic profiles and whole body energy metabolism. These observational
      changes in PBMC bioenergetics were most pronounced in those who had insufficient
      25(OH)D in winter. The data warrants confirmation through cause and effect study
      designs.

PMID- 28441629
TI  - Sex matters: The effects of biological sex on adipose tissue biology and energy
      metabolism.
AB  - Adipose tissue is a complex and multi-faceted organ. It responds dynamically to
      internal and external stimuli, depending on the developmental stage and activity
      of the organism. The most common functional subunits of adipose tissue, white and
      brown adipocytes, regulate and respond to endocrine processes, which then
      determine metabolic rate as well as adipose tissue functions. While the molecular
      aspects of white and brown adipose biology have become clearer in the recent
      past, much less is known about sex-specific differences in regulation and
      deposition of adipose tissue, and the specific role of the so-called pink
      adipocytes during lactation in females. This review summarises the current
      understanding of adipose tissue dynamics with a focus on sex-specific differences
      in adipose tissue energy metabolism and endocrine functions, focussing on
      mammalian model organisms as well as human-derived data. In females, pink
      adipocytes trans-differentiate during pregnancy from subcutaneous white
      adipocytes and are responsible for milk-secretion in mammary glands. Overlooking
      biological sex variation may ultimately hamper clinical treatments of many
      aspects of metabolic disorders.

PMID- 28441631
TI  - Up-regulated BAFF and BAFF receptor expression in patients with intractable
      temporal lobe epilepsy and a pilocarpine-induced epilepsy rat model.
AB  - PURPOSE: Some studies have suggested that BAFF and BAFFR are highly expressed in
      the central nervous system (CNS) and participate in inflammatory and immune
      associated diseases. However, whether BAFF and BAFFR are involved in the
      pathogenesis of epilepsy remains unknown. This study aimed to investigate the
      expression of BAFF and BAFFR proteins in the brains of patients with temporal
      lobe epilepsy (TLE) and in a pilocarpine-induced rat model of TLE to identify
      possible roles of the BAFF-BAFFR signaling pathway in epileptogenesis. METHODS:
      Real-time quantitative polymerase chain reaction (RT-qPCR), western blot,
      immunohistochemistry, and double-immunofluorescence were performed in this study.
      RESULTS: The results showed that BAFF and BAFFR expression levels were markedly
      up-regulated in intractable TLE patients and TLE rats. Moreover, BAFF and BAFFR
      proteins mainly highly expressed in the membranes and cytoplasms of the dendritic
      marker MAP2 in the cortex and hippocampus. CONCLUSION: Therefore, the significant
      increased in BAFF and BAFFR protein expression in both TLE patients and rats
      suggest that BAFF and BAFFR may play important roles in regulating the
      pathogenesis of epilepsy.

PMID- 28441632
TI  - Emergency computed tomography in patients with first seizure.
AB  - PURPOSE: To determine the frequency of emergent imaging findings on head computed
      tomography (CT) in an adult population of first seizure (FS) patients presenting
      to an emergency department (ED); and to search for associations between clinical
      features and emergent imaging findings among these patients. METHODS: For this
      retrospective registry-based study, adult FS patients presenting to Helsinki
      University Hospital ED in 2006 were identified based on ICD-10 diagnosis.
      Clinical parameters were extracted from patient records. A neuroradiologist
      blinded to clinical information reviewed the CT scans for emergent imaging
      findings prompting changes in acute treatment, predefined as intracranial
      haemorrhage, acute ischemia, central nervous system infection, mass effect,
      midline shift, obstructive hydrocephalus and/or brain oedema. RESULTS: 449 FS
      patients were identified, of which 416 (93%) had undergone emergency CT imaging.
      Of these, 49 (12%) had emergent imaging findings on non-contrast CT. Logistic
      regression suggested that headache (odds ratio (OR) 3.62, 95% confidence interval
      (CI) 1.30-10.12), focal motor sign in the ED (OR 3.23, 95% CI 1.58-6.62), history
      of malignancy (OR 3.05, 95% CI 1.17-7.92), and altered mental state in the ED (OR
      2.27, 95% CI 1.15-4.49) were associated with emergent imaging findings on NCCT.
      Presence of at least one of these factors had 84% sensitivity for emergent
      imaging findings. CONCLUSION: In FS patients, clinical information can be used to
      guide imaging decisions in the ED. However, if emergency imaging is not
      performed, urgent outpatient imaging and pre-imaging follow up should be secured.

PMID- 28441634
TI  - Spatial enhancement of ECG using diagnostic similarity score based lead selective
      multi-scale linear model.
AB  - In this work, a new patient-specific approach to enhance the spatial resolution
      of ECG is proposed and evaluated. The proposed model transforms a three-lead ECG
      into a standard twelve-lead ECG thereby enhancing its spatial resolution. The
      three leads used for prediction are obtained from the standard twelve-lead ECG.
      The proposed model takes advantage of the improved inter-lead correlation in
      wavelet domain. Since the model is patient-specific, it also selects the optimal
      predictor leads for a given patient using a lead selection algorithm. The lead
      selection algorithm is based on a new diagnostic similarity score which computes
      the diagnostic closeness between the original and the spatially enhanced leads.
      Standard closeness measures are used to assess the performance of the model. The
      similarity in diagnostic information between the original and the spatially
      enhanced leads are evaluated using various diagnostic measures. Repeatability and
      diagnosability are performed to quantify the applicability of the model. A
      comparison of the proposed model is performed with existing models that transform
      a subset of standard twelve-lead ECG into the standard twelve-lead ECG. From the
      analysis of the results, it is evident that the proposed model preserves
      diagnostic information better compared to other models.

PMID- 28441633
TI  - A health intervention or a kitchen appliance? Household costs and benefits of a
      cleaner burning biomass-fuelled cookstove in Malawi.
AB  - Pneumonia is the leading cause of mortality for children under five years in sub
      Saharan Africa. Household air pollution has been found to increase risk of
      pneumonia, especially due to exposure from dirty burning biomass fuels. It has
      been suggested that advanced stoves, which burn fuel more efficiently and reduce
      smoke emissions, may help to reduce household air pollution in poor, rural
      settings. This qualitative study aims to provide an insight into the household
      costs and perceived benefits from use of the stove in Malawi. It was conducted
      alongside The Cooking and Pneumonia Study (CAPS), the largest village cluster
      level randomised controlled trial of an advanced combustion cookstove
      intervention to prevent pneumonia in children under five to date. In 2015, using
      100 semi-structured interviews this study assessed household time use and
      perceptions of the stove from both control and intervention participants taking
      part in the CAPS trial in Chilumba. Household direct and indirect costs
      associated with the intervention were calculated. Users overwhelming liked using
      the stove. The main reported benefits were reduced cooking times and reduced fuel
      consumption. In most interviews, the health benefits were not initially
      identified as advantages of the stove, although when prompted, respondents stated
      that reduced smoke emissions contributed to a reduction in respiratory symptoms.
      The cost of the stove was much higher than most respondents said they would be
      willing to pay. The stoves were not primarily seen as health products.
      Perceptions of limited impact on health was subsequently supported by the CAPS
      trial data which showed no significant effect on pneumonia. While the findings
      are encouraging from the perspective of acceptability, without innovative
      financing mechanisms, general uptake and sustained use of the stove may not be
      possible in this setting. The findings also raise the question of whether the
      stoves should be marketed and championed as 'health interventions'.

PMID- 28441635
TI  - Validation of SmartRank: A likelihood ratio software for searching national DNA
      databases with complex DNA profiles.
AB  - Searching a national DNA database with complex and incomplete profiles usually
      yields very large numbers of possible matches that can present many candidate
      suspects to be further investigated by the forensic scientist and/or police.
      Current practice in most forensic laboratories consists of ordering these 'hits'
      based on the number of matching alleles with the searched profile. Thus,
      candidate profiles that share the same number of matching alleles are not
      differentiated and due to the lack of other ranking criteria for the candidate
      list it may be difficult to discern a true match from the false positives or
      notice that all candidates are in fact false positives. SmartRank was developed
      to put forward only relevant candidates and rank them accordingly. The SmartRank
      software computes a likelihood ratio (LR) for the searched profile and each
      profile in the DNA database and ranks database entries above a defined LR
      threshold according to the calculated LR. In this study, we examined for mixed
      DNA profiles of variable complexity whether the true donors are retrieved, what
      the number of false positives above an LR threshold is and the ranking position
      of the true donors. Using 343 mixed DNA profiles over 750 SmartRank searches were
      performed. In addition, the performance of SmartRank and CODIS were compared
      regarding DNA database searches and SmartRank was found complementary to CODIS.
      We also describe the applicable domain of SmartRank and provide guidelines. The
      SmartRank software is open-source and freely available. Using the best practice
      guidelines, SmartRank enables obtaining investigative leads in criminal cases
      lacking a suspect.

PMID- 28441636
TI  - Psychological features and quality of life in 50 adult patients with epilepsy and
      their caregivers from the Lecco epilepsy center, Italy.
AB  - Epilepsy is one of the most common neurological disorders. To the best of our
      knowledge, in Italy, the relationship between patients' and caregivers'
      psychological state has rarely been analyzed. Thus, we sought to evaluate both
      the psychological state of patients with epilepsy and that of their caregivers
      and the interrelationship between them. We also assessed the existing relation
      between psychological features and some clinical and demographic information,
      such as number of antiepileptic drugs (AEDs), epilepsy duration and education
      level of patients and their caregivers. We enrolled in the study 50 consecutive
      adult patients attending the epilepsy clinic of "A. Manzoni" Hospital and their
      caregivers. Both patients and their caregivers were administered Hospital Anxiety
      and Depression Scale (HADS) and 36-item Short-Form Health Survey (SF-36).
      Anxiety, depression and quality of life values of both patients and their
      caregivers did not differ significantly from the normative samples. No
      statistically significant correlation between epilepsy duration and patients' and
      caregivers' psychological features was found. Patients which took more than one
      AED reported lower values of "Vitality" (p <.05) and "Social Functioning" (p
      <.05) than their own caregivers. Caregivers with higher education level presented
      lower "Vitality" values than caregivers with lower education level (p <.05).
      Patients with pharmacoresistant seizures reported lower values of "Mental Health"
      than patients with non-pharmacoresistant seizures (p <.05). In this context, the
      role of coping mechanisms by patients and caregivers may explain apparently
      unexpected findings and suggests that strategies aimed at reinforcing them may be
      effective in selected cases. Therefore, while the severity of epilepsy may have
      an impact on the psychological state of adult patients with epilepsy and their
      caregivers, our results highlight the role of multidimensional determinants,
      including stigma. Further studies are needed to identify the factors related to
      epilepsy, patients, caregivers, treatments, and the environment that may be
      modifiable in order to improve self-perceived QoL.

PMID- 28441637
TI  - Subtle pathological changes in neocortical temporal lobe epilepsy.
AB  - : This was a prospective observational study to correlate the clinical symptoms,
      electrophysiology, imaging, and surgical pathology of patients with temporal lobe
      epilepsy (TLE) without hippocampal sclerosis. We selected consecutive patients
      with TLE and normal MRI undergoing temporal lobe resection between April and
      September 2015. Clinical features, imaging, and functional data were reviewed.
      Intracranial monitoring and language mapping were performed when it was required
      according to our team recommendation. Prior to hippocampal resection,
      intraoperative electrocorticography was performed using depth electrodes in the
      amygdala and the hippocampus. The resected hippocampus was sent for pathological
      analysis. RESULTS: Five patients with diagnosis with non-lesional TLE were
      included. We did not find distinctive clinical features that could be a
      characteristic of non-lesional TLE. The mean follow-up was 13.2months (11
      15months); 80% of patients achieved Engel Class I outcome. There was no
      distinctive electrographic findings in these patients. Histopathologic analysis
      was negative for mesial temporal sclerosis. A second blinded independent
      neuropathologist with expertise in epilepsy found ILAE type I focal cortical
      dysplasia in the parahippocampal gyrus in all patients. A third independent
      neuropathologist reported changes in layer 2 with larger pyramidal neurons in 4
      cases but concluded that none of these cases met the diagnostic criteria of FCD.
      Subtle pathological changes could be associated with a parahippocampal epileptic
      zone and should be investigated in patients with MRI-negative TLE. This study
      also highlights the lack of interobserver reliability for the diagnosis of mild
      cortical dysplasia. Finally, selective amygdalo-hippocampectomy or laser ablation
      of the hippocampus may not control intractable epilepsy in this specific
      population.

PMID- 28441638
TI  - Health risk assessment for the consumption of fresh and preserved fish (Alosa
      agone) from Lago di Como (Northern Italy).
AB  - BACKGROUND: Although banned in many countries for decades, DDTs and PCBs still
      represent a global threat to food safety. As these contaminants are still present
      in aquatic ecosystems, fish can be an important contributor to their total
      dietary intake. OBJECTIVES: Alosa agone specimens were sampled over a period of
      10 years (from 2006 to 2015) to provide a representative overview of the DDT and
      PCB levels of Lago di Como, a deep Italian lake where a DDT input due to
      secondary sources was observed in recent years. The potential health risk from
      the consumption of both fresh and preserved fish was evaluated. RESULTS: While
      DDT levels have generally decreased during the monitored period, reaching quite
      stable levels, PCB concentrations were variable, with values exceeding, in some
      cases, the European Union limit for human consumption and enabling potential
      carcinogenic effects. However, typical local processing of this fish species
      markedly appeared to decrease these contaminant levels, thus making the fish
      product (called missoltino) a safer food. CONCLUSIONS: The results of this work
      highlighted the need of continuous biomonitoring of those contaminants considered
      a past issue along with the emergent ones.

PMID- 28441639
TI  - Antecubital Fossa Venous Access For Right Heart Catheterization.
AB  - With the advance of radial access and ulnar access there has been an increased
      interest in performing right heart catheterization (RHC) and right-heart based
      procedures via antecubital venous access. Our purpose is to describe the venous
      anatomy of the upper extremities, technique, equipment, and cost for employing
      this approach. Reported also is the international experience based on
      publications assessing procedural success, complications, fluoroscopy time and
      radiation dose, access-site compression time, and time to ambulation. We conclude
      that antecubital-venous-access based RHC carries satisfactory success rates,
      requires a short learning curve, and is exceptionally safe even when performed
      with full anticoagulation. It is our hope that industry will provide us with even
      better tools to extend the practice of antecubital-venous-access based procedures
      and interventions.

PMID- 28441640
TI  - Lack of Association Between Limb Hemodynamics and Response to Infrapopliteal
      Endovascular Therapy in Patients With Critical Limb Ischemia.
AB  - BACKGROUND: Non-invasive limb hemodynamics may aid in diagnosis of critical limb
      ischemia (CLI), although the relationship with disease severity and response to
      endovascular therapy is unclear. METHODS AND RESULTS: This prospective, single
      center study enrolled 100 CLI patients (Rutherford class 4-6) who underwent
      infrapopliteal endovascular revascularization (175 lesions) in the Peripheral
      RegIstry of Endovascular Clinical OutcoMEs (PRIME) registry. Hemodynamic measures
      included ankle-brachial index (ABI), toe-brachial index (TBI), and toe pressure
      (TP). Procedure success following revascularization was defined as stenosis
      <=30%. Hemodynamic success was defined as an increase >0.15 in ABI or TBI
      relative to baseline. Freedom from amputation was defined as no major or minor
      amputation during follow-up. Clinical success was defined as a decrease of at
      least one Rutherford class during follow-up. Treatment success was defined as
      procedure success, freedom from amputation, and clinical improvement. Median
      baseline hemodynamic values were 0.90 for ABI, 0.39 for TBI, and 54 mm Hg for TP.
      Twenty-nine patients (29%) did not meet the common hemodynamic diagnostic
      criterion for eligibility in CLI trials (ABI <=0.5, TBI <=0.5, or TP <50 mm Hg).
      Main outcomes included 96% procedure success, 95% freedom from amputation, 64%
      clinical success, and 62% treatment success. There was no relationship between
      baseline (or with the pretreatment to posttreatment change) limb hemodynamic
      values and the response to infrapopliteal endovascular therapy. CONCLUSION: Non
      invasive hemodynamic studies may have limited clinical usefulness in patients
      with CLI. The usefulness of these parameters to confirm eligibility and to assess
      response to therapy in interventional CLI clinical trials should be re-evaluated.

PMID- 28441641
TI  - Low-Volume Contrast CT Angiography Via Pulmonary Artery Injection for Measurement
      of Aortic Annulus in Patients Undergoing Transcatheter Aortic Valve Replacement.
AB  - OBJECTIVES: To investigate the feasibility and image quality of low-dose contrast
      computed tomography (CT) angiography with pulmonary artery (PA) protocol.
      BACKGROUND: Aortic stenosis is the most common valvular heart disease and
      transcatheter aortic valve replacement (TAVR) has evolved as an alternative
      method for surgical valve replacement in intermediate-risk and high-risk surgical
      patients. CT is essential for measurement of aortic annulus prior to TAVR.
      METHODS: Twenty patients underwent a low-dose contrast study with PA protocol and
      20 patients underwent a traditional-dose study (traditional protocol). In PA
      protocol, the pigtail catheter was advanced in the main pulmonary artery under
      fluoroscopic guidance, with a second pigtail placed in the abdominal aorta. The
      pigtail catheter and sheath were secured in position and the patient was taken to
      the CT scan area for CT angiography of the chest (with injection from the PA
      catheter), abdomen, and pelvis (with injection from abdominal aortic catheter).
      RESULTS: The amount of contrast used was significantly lower in the PA protocol
      vs the traditional protocol (40 mL vs 99.50 +/- 6.87 mL; P<.001) at the cost of
      reduced average signal (265 +/- 60 HU vs 371 +/- 70 HU; P<.001), but without
      affecting measurements of the aortic annulus. Furthermore, no statistically
      significant difference in serum creatinine concentration was observed before and
      48 hours after contrast administration in the PA group. CONCLUSION: Our data
      provide evidence that the new PA technique can be performed safely with much
      lower volume of CT contrast without affecting assessment of aortic annulus size.

PMID- 28441642
TI  - First-in-Man Percutaneous Transaxillary Artery Placement and Removal of the
      Impella 5.0 Mechanical Circulatory Support Device.
AB  - We report on the fully percutaneous insertion and removal of the Impella 5.0
      microaxial flow device via the axillary artery in a patient with cardiogenic
      shock and peripheral artery disease. Due to inadequate iliofemoral vasculature
      and desire for mobility, the axillary artery was felt to be the most appropriate
      access approach for temporary mechanical circulatory support. The procedure was
      well tolerated and the patient was supported for 17 days, at which time the
      device was safely removed in a fully percutaneous manner at the time of permanent
      left ventricular assist device placement. Percutaneous transaxillary placement of
      the Impella 5.0 device is a feasible support option in cardiogenic shock in
      patients with hostile iliofemoral disease.

PMID- 28441643
TI  - Ventricular Rupture Following Myocardial Infarction.
AB  - A 70-year-old man presented with prolonged cardiac chest pain and was awaiting
      coronary artery bypass surgery following angiography showing extensive
      multivessel disease. Following further chest pain, cardiac magnetic resonance
      imaging showed extensive, contained, ventricular rupture, which was managed
      aggressively with combined bypass surgery and rupture repair.

PMID- 28441644
TI  - Management of Guidewire Entrapment With Laser Atherectomy.
AB  - A 62-year-old man was referred for percutaneous coronary intervention of a severe
      circumflex lesion. The guidewire became entangled in the previously implanted
      left anterior descending artery stent. The left main was engaged with a second
      guide catheter, followed by balloon dilations, various microcatheters, and laser
      atherectomy. The wire eventually fractured without protruding into the aorta. The
      circumflex lesion was stented with two stents, followed by left main stenting
      that covered the fragment. Caution should be used when wiring through stents;
      wire fracture can be treated with stent implantation, as long as the wire
      fragment does not protrude into the aorta.

PMID- 28441645
TI  - Saphenous Vein Graft Aneurysm 10 Years After Paclitaxel-Eluting Stent
      Implantation.
AB  - A patient underwent paclitaxel-eluting implantation for a saphenous vein graft
      stenosis. A follow-up angiogram at 8 months demonstrated no restenosis, with
      multifocal peristent contrast staining. After 10 years, a saphenous vein graft
      aneurysm was revealed within the stented segment. This late complication should
      be kept in mind when evaluating patients who have received prior drug-eluting
      stents.

PMID- 28441646
TI  - Spontaneous Regression of Possible Transcatheter Aortic Valve Thrombosis Without
      Additional Anticoagulant: Two-Year Follow-Up.
AB  - An 84-year-old man with symptomatic severe aortic stenosis received transcatheter
      aortic valve implantation (TAVI). Dual-antiplatelet therapy was continued for 6
      months post TAVI, and aspirin alone was used thereafter. Four-dimensional
      multidetector computed tomography revealed a new hypoattenuated leaflet
      thickening (HALT) with reduced leaflet motion at 1 year, considered to indicate
      leaflet thrombosis. At the 2-year follow-up, leaflet mobility had improved, with
      spontaneous regression of HALT. This is the first report of confirmed spontaneous
      regression of possible transcatheter heart valve thrombosis and recovery of
      leaflet mobility without the need for additional anticoagulant.

PMID- 28441647
TI  - Subjective Memory in a National Sample: Predicting Psychological Well-Being.
AB  - BACKGROUND: Individual perception of memory performance (i.e., subjective memory)
      is assessed using a variety of approaches. This article focuses on 2 such
      approaches: (1) self-comparison assessments that attempt to capture changes in
      memory ability over a period of time and (2) age-anchored comparisons that assess
      how an individual perceives their memory in relation to others their age. These
      different types of assessment may relate to psychological well-being differently
      due to the underlying mechanisms of assessment. OBJECTIVE: The purpose of these
      analyses is to examine 2 measures of subjective memory (i.e., a self-comparison
      measure and an age-anchored comparison measure) as predictors of psychological
      well-being among adults in mid- and late life. METHODS: Participants (n = 3,434)
      in the Midlife in the United States Study completed measures of subjective
      memory, depressive affect, and life satisfaction. Structural equation modeling
      was used to examine whether the self-comparison and age-anchored comparison
      measures had differential predictive utility regarding psychological well-being.
      RESULTS: Higher age-anchored comparison ratings were related to higher life
      satisfaction scores. There was a significant interaction between the 2 items such
      that individuals with lower ratings on both subjective memory measures had the
      poorest outcomes. Additionally, age-anchored comparisons interacted with age:
      older adults had the poorest outcomes when they reported poorer age-anchored
      comparisons. CONCLUSION: These findings highlight the importance of precise
      measurement in the consideration of subjective memory. How an individual was
      asked to rate his or her perception of memory influenced the relationships
      between subjective memory and psychological well-being. This study contributes
      valuable insight into the importance of the assessment models of subjective
      memory.

PMID- 28441648
TI  - The Epigenetic Regulation of GATA4-Dependent Brain Natriuretic Peptide Expression
      during Alcohol Withdrawal.
AB  - OBJECTIVE: Natriuretic peptides participate in the collection of metabolic
      effects during alcohol withdrawal. Having witnessed modulation of other
      natriuretic peptides in alcohol-dependent patients during alcohol withdrawal, we
      were interested in the relation of brain natriuretic peptide (BNP) methylation
      with protein expression and craving in this longitudinal study. METHODS: Ninety
      nine male patients were compared to 101 healthy controls concerning epigenetic
      regulation and protein expression during detoxification treatment. RESULTS: With
      BNP expression being GATA4 dependent, we observed a correlation of GATA4 binding
      site methylation and protein expression. BNP serum levels and Obsessive
      Compulsive Drinking Scale scores are significantly decreased during withdrawal.
      Focusing on the two CpGs that are between GATA transcription factor binding
      sites, statistical analysis revealed a reversely proportional methylation
      pattern, significantly increasing with ongoing detoxification and thereby
      supporting the observed serum level changes. CONCLUSION: Without the functional
      knowledge about regulation of BNP expression via the GATA transcription factor,
      it would have been easy to take the mean results of the global CpG data and
      propose a direct relationship between methylation and expression. Thus, these
      findings are a voice for functionally and mechanistically approved results. There
      was no causal relationship between protein expression levels and epigenetic
      changes. Further research is needed which includes protein expression and other
      approaches.

PMID- 28441649
TI  - Home-Based Physical Behavior in Late Stage Parkinson Disease Dementia:
      Differences between Cognitive Subtypes.
AB  - BACKGROUND: For the early diagnosis of Parkinson disease dementia (PDD),
      objective home-based tools are needed to quantify even mild stages of dysfunction
      of the activities of daily living (ADL). OBJECTIVES: In this pilot study, home
      based physical behavior was assessed to examine whether it is possible to
      distinguish mild cognitive impairment (PD-MCI) from PDD. METHODS: Fifty-five
      patients with mild to severe Parkinson disease (PD) participated in this cross
      sectional study. Based on comprehensive neuropsychological testing, PD patients
      were classified as cognitively nonimpaired (PD-NC), PD-MCI or PDD. For physical
      behavior assessments, patients wore the accelerometer DynaPort(r) (McRoberts) for
      3 days. Ordinal logistic regression models with continuous Y were applied to
      correct results for motor impairment and depressive symptoms. RESULTS: After
      excluding 7 patients due to insufficient wearing time, 48 patients with a mean of
      2 recorded days were analyzed (17 PD-NC, 22 PD-MCI, 9 PDD). ADL-impaired PDD
      patients showed fewer sedentary bouts than non-ADL-impaired PD-MCI (p = 0.01,
      odds ratio [OR] = 8.9, 95% confidence interval [CI] = 1.8-45.2) and PD-NC (p =
      0.01, OR = 10.3, CI = 1.6-67.3) patients, as well as a longer sedentary bout
      length (PD-NC: p = 0.02, OR = 0.1, CI = 0.02-0.65; PD-MCI: p = 0.02, OR = 0.14,
      CI = 0.03-0.69). These differences were mainly caused by fewer (PD-NC: p = 0.02,
      OR = 9.6, CI = 1.5-62.4; PD-MCI: p = 0.01, OR = 8.5, CI = 1.5-37.3) but longer
      sitting bouts (PD-NC: p = 0.03, OR = 0.12, CI = 0.02-0.80; PD-MCI: p = 0.04, OR =
      0.19, CI = 0.04-0.93). Tests assessing executive function, visuoconstruction and
      attention correlated significantly with specific activity parameters (rho >= 0.3;
      p < 0.05). CONCLUSION: Objective assessment of physical behavior, in particular
      the detection of sedentary bouts, is a promising contributor to the
      discrimination between PD-MCI and PDD.

PMID- 28441651
TI  - Serum Creatinine: Not So Simple!
AB  - Measuring serum creatinine is cheap and commonly done in daily practice. However,
      interpretation of serum creatinine results is not always easy. In this review, we
      will briefly remind the physiological limitations of serum creatinine due notably
      to its tubular secretion and the influence of muscular mass or protein intake on
      its concentration. We mainly focus on the analytical limitations of serum
      creatinine, insisting on important concept such as reference intervals,
      standardization (and IDMS traceability), analytical interferences, analytical
      coefficient of variation (CV), biological CV and critical difference. Because the
      relationship between serum creatinine and glomerular filtration rate is
      hyperbolic, all these CVs will impact not only the precision of serum creatinine
      but still more the precision of different creatinine-based equations, especially
      in low or normal-low creatinine levels (or high or normal-high glomerular
      filtration rate range).

PMID- 28441650
TI  - MicroRNA-1185 Induces Endothelial Cell Apoptosis by Targeting UVRAG and KRIT1.
AB  - BACKGROUND/AIMS: Atherosclerosis is a multifactorial chronic disease and is the
      main cause of death and impairment in the world. Endothelial injury and apoptosis
      play a crucial role in the onset and development of atherosclerosis. MicroRNAs
      (miRNAs) have been proven to be involved in the pathogenesis of atherosclerosis.
      However, studies of the functional role of apoptosis-related miRNAs in the
      endothelium during atherogenesis are limited. METHODS: Cell injury and apoptosis
      were measured in five types of cells transfected with miR-1185 or co-transfected
      with miR-1185 and its inhibitor. Bioinformatics analysis and a luciferase
      reporter assay were used to confirm the targets of miR-1185. The effects of the
      targets of miR-1185 on endothelial apoptosis were determined using small
      interfering RNA. RESULTS: In this study, we first report that miR-1185
      significantly promoted apoptosis in endothelial cells but not in vascular smooth
      muscle cells and macrophages. A mechanistic analysis showed that ultraviolet
      irradiation resistance-associated gene (UVRAG) and krev1 interaction trapped gene
      1 (KRIT1), targets of miR-1185, mediated miR-1185-induced endothelial cell
      apoptosis. CONCLUSION: The results revealed the impact of miR-1185 on endothelial
      apoptosis, suggesting that miR-1185 may be a potential target for the prevention
      and treatment of atherosclerosis.

PMID- 28441652
TI  - Ultraviolet A1 Phototherapy in the Treatment of Early Mycosis Fungoides.
AB  - BACKGROUND: Phototherapy has been the mainstay of therapies for early mycosis
      fungoides (MF). The beneficial role of ultraviolet (UV) light on MF is suggested
      by the observation that lesions occur on non-sun-exposed areas. Therapeutic light
      sources that are available today are broadband UVB, psoralen and UVA, narrowband
      UVB, and long-wave UV (UVA1). Current literature provides increasing evidence on
      the use of UVA1 to treat MF. AIM: To investigate the treatment responses of early
      MF patients treated with fixed 30 J/cm2 doses of UVA1 phototherapy. MATERIAL AND
      METHODS: Nineteen patients with early MF, stage IA-IIA of the TNM staging system,
      received fixed 30 J/cm2 doses of UVA1, given 5 times weekly over 5 weeks.
      Therapeutic effectiveness was assessed by clinical examination and was confirmed
      by histological evaluation. RESULTS: Of the 19 patients, complete responses were
      achieved in 12 (63%) and partial responses were achieved in 7 (37%) patients
      after UVA1 radiation exposures. During the study, UVA1 therapy was well
      tolerated. During the follow-up, 7 (58%) of the 12 patients with complete
      response relapsed within 3 months of the UVA1 therapy. CONCLUSION: The current
      study provides clinical and histological evidence for the effectiveness of UVA1
      (30 J/cm2 5 times a week for 5 weeks) as a skin-directed therapy in the treatment
      of early MF; however, such a treatment failed to maintain a long and sustained
      response. Thus, studies to identify the optimal dosing protocol regarding the
      therapeutic efficacy, the factors affecting relapse time/rate, and the necessity
      of maintenance treatment are needed.

PMID- 28441653
TI  - Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and
      Barrier Function during Hemorrhagic Shock in Dogs.
AB  - BACKGROUND: Topical drug application is used to avoid systemic side effects. The
      aim of this study was to analyze whether locally applied iloprost or
      nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier
      function during physiological and hemorrhagic conditions. METHODS: In repeated
      experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal
      saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro
      and microcirculatory variables were recorded continuously. Gastric barrier
      function was assessed via translocation of sucrose into the blood. RESULTS:
      During hemorrhage, gastric mucosal oxygenation decreased from 77 +/- 4 to 37 +/-
      7%. This effect was attenuated by nitroglycerin (78 +/- 6 to 47 +/- 13%) and
      iloprost (82 +/- 4 to 54 +/- 9%). Sucrose plasma levels increased during
      hemorrhage from 7 +/- 4 to 55 +/- 15 relative amounts. This was alleviated by
      nitroglycerin (5 +/- 8 to 29 +/- 38 relative amounts). These effects were
      independent of systemic hemodynamic variables. CONCLUSIONS: During hemorrhage,
      topical nitroglycerin and iloprost improve regional gastric oxygenation without
      affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the
      mucosal barrier integrity. Thus, local drug application improves gastric
      microcirculation without compromising systemic hemodynamic variables, and it may
      also protect mucosal barrier function.

PMID- 28441654
TI  - Gastric Ulcer Hemorrhage - a Potential Life-Threatening Complication of
      Intragastric Balloon Treatment of Obesity.
AB  - BACKGROUND: Some morbidly obese patients do not qualify for bariatric surgery due
      to general health contraindications. Intragastric balloon treatment might be a
      therapeutic option in the above-mentioned cases. It can prime super-obese
      patients with end-stage disease for bariatric surgery. As a neoadjuvant therapy
      before surgery, it leads to a downstage of the disease by preliminary weight
      reduction, to an improvement in general health and, in summary, to a reduction of
      the perioperative risk. It is generally considered to be a safe method. However,
      due to the wide range of possible complications and unusual symptoms after
      intragastric balloon treatment, an interdisciplinary, instead of only a surgical
      or endoscopic, treatment and follow-up might be recommended in these patients.
      CASE REPORT: We here describe a potential life-threatening complication in the
      form of gastric bleeding as a consequence of intragastric balloon treatment and
      simultaneous aspirin taking and Helicobacter pylori infection. CONCLUSION: There
      have been reports of some complications of intragastric balloon treatment.
      However, to the best of our knowledge there were no reports concerning life
      threatening hemorrhage from gastric ulcer.

PMID- 28441655
TI  - Cutaneous Complications Related to Tattoos: 31 Cases from Finland.
AB  - BACKGROUND: Cutaneous complications related to permanent tattoos affect 2-30% of
      those patients who have tattooed their skin. Little is known about the cases of
      tattoo complications in Finland. OBJECTIVE: The aim of this study was to conduct
      a retrospective review of a series of Finnish patients with cutaneous tattoo
      reactions. METHODS: We collected cases of tattoo reactions from the Department of
      Dermatology at Helsinki University Central Hospital, from members of the Finnish
      dermatological society and from various other sources (author's private practice,
      tattooists, professional internet forum). We analysed the demographics, clinical
      presentation, diagnosis, and microscopic findings on the skin biopsies, and
      evaluated the therapeutic outcome. RESULTS: Thirty-one patients (16 men and 15
      women, mean age 37.8) were included from 9 cities, mainly from Helsinki. Fifty
      two percent (16/31) presented with an allergic tattoo reaction mainly against the
      red colour (75%, 12/16). Reactions were clinically polymorph ranging from
      scattered papules or nodules to complete infiltration of a colour. Lesions were
      itchy and sometimes painful. The reactions were lichenoid, granulomatous,
      pseudolymphomatous or less specific with a dermal lympho-histiocytic or
      plasmocytic infiltrate. Other diagnoses included tattoo blow-out (13%), melanoma
      within a tattoo, naevi within a tattoo (10% each), lichen planus (6%),
      granulomatous reaction with uveitis, sarcoidosis and dermatofibroma (3% each).
      Allergic tattoo reactions were mainly treated with local corticosteroid (CS)
      ointments, CS infiltration or surgical removal. CONCLUSION: This review is the
      largest series of tattoo complications in the Baltic area. It illustrates the
      wide spectrum of complications. Prospective, controlled therapeutic studies are
      necessary to assess the best treatment protocols for tattoo allergies and tattoo
      reaction management in general.

PMID- 28441656
TI  - Development of a Smartphone App for Visualizing Heart Sounds and Murmurs.
AB  - BACKGROUND: Auscultation is one of the basic techniques for the diagnosis of
      heart disease. However, the interpretation of heart sounds and murmurs is a
      highly subjective and difficult skill. OBJECTIVES: To assist the auscultation
      skill at the bedside, a handy phonocardiogram was developed using a smartphone
      (Samsung Galaxy J, Android OS 4.4.2) and an external microphone attached to a
      stethoscope. METHODS AND RESULTS: The Android app used Java classes,
      "AudioRecord," "AudioTrack," and "View," that recorded sounds, replayed sounds,
      and plotted sound waves, respectively. Sound waves were visualized in real-time,
      simultaneously replayed on the smartphone, and saved to WAV files. To confirm the
      availability of the app, 26 kinds of heart sounds and murmurs sounded on a human
      patient simulator were recorded using three different methods: a bell-type
      stethoscope, a diaphragm-type stethoscope, and a direct external microphone
      without a stethoscope. The recorded waveforms were subjectively confirmed and
      were found to be similar to the reference waveforms. CONCLUSIONS: The real-time
      visualization of the sound waves on the smartphone may help novices to readily
      recognize and learn to distinguish the various heart sounds and murmurs in real
      time.

PMID- 28441657
TI  - Involvement of the Multidrug and Toxic Compound Extrusion Transporter in
      Testosterone Release from Cultured Pig Leydig Cells.
AB  - Testosterone is considered to be released from Leydig cells via passive diffusion
      because of its hydrophobicity; however, the exact mechanism underlying
      testosterone secretion and the transporter involved are both unknown. Multidrug
      and toxic compound extrusion (MATE) transporters are predominantly found in the
      kidneys and liver and are thought to function in the elimination of metabolic
      organic cations during the final step of excretion in the kidney. In contrast,
      mMATE2 has been shown to be predominantly expressed in testicular Leydig cells.
      Although the physiological function of mMATE2 in Leydig cells is unknown, we
      hypothesized that mMATE2 acts as a testosterone exporter and is responsible for
      the secretion of testosterone from Leydig cells. Therefore, in the present study,
      we investigated the involvement of the MATE transporter in testosterone secretion
      from pig Leydig cells. Immunohistochemical analysis with anti-pig MATE2 antiserum
      indicated that the MATE transporter is present in pig Leydig cells. Additionally,
      treatment with the MATE inhibitors cimetidine and pyrimethamine reduced the
      testosterone secretion from pig Leydig cells but increased the intracellular
      testosterone levels. Estradiol release and intracellular estradiol level induced
      by human chorionic gonadotropin (hCG) further increased with cimetidine
      treatment. These results indicated that testosterone produced by hCG treatment is
      secreted from Leydig cells via the MATE transporter; however, in the presence of
      cimetidine or pyrimethamine, this MATE transporter-mediated secretion was
      inhibited, resulting in increased intracellular testosterone levels and estradiol
      production in Leydig cells. Thus, the MATE transporter may be responsible for
      testosterone secretion from Leydig cells.

PMID- 28441658
TI  - Risk Factors for Anastomotic Leakage of Esophagojejunostomy after Laparoscopy
      Assisted Total Gastrectomy for Gastric Cancer.
AB  - BACKGROUND/AIMS: The study aimed to clarify the risk factors for anastomotic
      leakage after laparoscopy-assisted total gastrectomy (LATG) for gastric cancer.
      METHODS: In this study, we enrolled 131 patients with preoperatively diagnosed
      early gastric cancer who underwent LATG by a single surgeon between June 2006 and
      February 2014 at the Department of Surgery, Gastroenterological Center, Yokohama
      City University. Risk factors for anastomotic leakage (esophagojejunostomy) after
      LATG were retrospectively evaluated by univariate and multivariate analyses.
      RESULTS: Anastomotic leakage of the esophagojejunostomy was observed in 13 (9.9%)
      of 131 patients. Univariate analysis of risk factors for anastomotic leakage
      revealed that the prognostic nutritional index (PNI) is a risk factor for
      anastomotic leakage (<55, 11 of 63 vs. >=55, 2 of 55; p = 0.039). Multivariate
      analysis revealed that PNI is an independent risk factor for anastomotic leakage
      (OR 0.208; 95% CI 0.044-0.981; p = 0.047). CONCLUSION: Gastric cancer patients
      with a low PNI have a higher risk for anastomotic leakage after LATG. The results
      of this study must be confirmed by a study with a large cohort of patients
      receiving LATG reconstructed using the same method by experienced surgeons in
      multiple institutions.

PMID- 28441659
TI  - Perioperative Serum Carcinoembryonic Antigen Levels Predict Recurrence and
      Survival of Patients with Pathological T2-4 Gastric Cancer Treated with Curative
      Gastrectomy.
AB  - BACKGROUND/AIMS: Do serum carcinoembryonic antigen (CEA) and carbohydrate antigen
      (CA) 19-9 levels serve as prognostic indicators in patients with gastric cancer
      (GC)? This is a question that has long been disputed. The aim of this study was
      to evaluate the significance of perioperative serum levels of CEA and CA19-9 for
      predicting the recurrence and long-term survival after patients with pT2-4 GC
      undergo curative gastrectomy. METHODS: This study included 251 patients with
      radically resected pT2-4 GC without preoperative treatment. Associations between
      the preoperative and postoperative serum levels of CEA or CA19-9 and
      postoperative long-term outcomes and recurrence patterns were evaluated. RESULTS:
      Preoperative CEA >5.0 ng/mL was an independent prognostic factor of overall
      survival. Elevation of both preoperative CEA and CA19-9 levels showed no
      synergistic adverse effects on prognosis. Preoperative levels of these markers
      achieved superior predictive performance compared with the postoperative values.
      Adverse prognosis is significantly associated with persistent elevation of CEA
      levels before and after gastrectomy. Elevation of CEA levels, particularly at
      postoperative measurement, was significantly associated with hematogenous
      recurrence. CONCLUSION: Determination of perioperative CEA levels facilitated
      predictions of recurrence patterns and prognosis among patients with pT2-4 GC who
      underwent curative gastrectomy.

PMID- 28441660
TI  - The Phenotype and Outcome of Infantile Cardiomyopathy Caused by a Homozygous
      ELAC2 Mutation.
AB  - OBJECTIVE: Cardiomyopathy (CMP) in children is a clinically and genetically
      heterogeneous group of disorders. Disease-associated mutations have been
      identified in more than 50 genes. Recently, mutations in the mitochondrial tRNA
      processing gene, ELAC2, were reported to be associated with the recessively
      inherited form of hypertrophic CMP (HCM). This study is aimed at describing the
      cardiac phenotype and outcome of ELAC2 mutation. METHODS: We performed whole
      exome sequencing followed by targeted mutation screening to identify the genetic
      etiology of severe infantile-onset CMP in 64 consanguineous Saudi families.
      RESULTS: A previously reported mutation (p.Phe154Leu) in ELAC2 gene was detected
      in 16 families. The index cases presented between 2 and 7 months of age with HCM
      in 13 infants and dilated CMP (DCM) in 3. Pericardial effusion was observed in 7
      infants (44%). All infants died with a median age of death of 4 months. Almost
      1/3 of them died during the initial presentation. CONCLUSION: Our study suggests
      screening the ELAC2 gene in severe infantile-onset HCM or DCM of unknown
      etiology, especially in the presence of pericardial effusion. Our work
      demonstrates a universally poor outcome of the (p.Phe154Leu) variant in ELAC2
      gene; a correlation that helps in counseling parents and in planning appropriate
      medical intervention.

PMID- 28441661
TI  - Defective Platelet Activation and Bleeding Complications upon Cholestasis in
      Mice.
AB  - BACKGROUND/AIMS: Platelets are essential mediators of hemostasis to avoid
      excessive blood loss. Cirrhosis and chronic liver diseases are characterized by
      alterations in hemostasis. Alterations in the secondary hemostasis have been well
      studied, while defects in primary hemostasis, especially the consequences of
      cholestatic liver disease on platelet function are not well defined. METHODS:
      After bile duct ligation (BDL) platelet activation and thrombus formation were
      analyzed in mice. RESULTS: BDL in mice had a moderate effect on platelet counts;
      however, intrinsic platelet activation was strongly reduced upon activation of
      the collagen receptor GPVI at early time points. 7 days after bile duct ligation,
      platelets displayed an almost complete loss of activation with reduced agonist
      triggered release of alpha and dense granules and expression of integrin
      alphaIIbbeta3 on the platelet surface. This activation defects resulted in
      strongly reduced thrombus formation under flow, reduced platelet adhesion to
      fibrinogen and bleeding complications in BDL mice as measured by tail bleeding
      experiments. Mechanistically, elevated nitric oxide and prostacyclin levels
      induced phosphorylation of Vasodilator-stimulated phosphoprotein (VASP), an
      established inhibitor of platelet activation. Furthermore increased tissue
      plasminogen activator in plasma of BDL mice led to enhanced plasmin levels that
      might be responsible for reduced glycoprotein expression of BDL platelets.
      Besides, high amounts of bile acids contribute to defective signal transduction
      as shown in platelets from mice fed with a cholic acid diet. CONCLUSIONS:
      Cholestatic liver disease induces multiple platelet activation defects and
      impairs thrombus formation responsible for bleeding complications at least in
      mice.

PMID- 28441662
TI  - Buffalo Leukemia Inhibitory Factor Induces Differentiation and Dome-Like
      Secondary Structures in COS-1 Cells.
AB  - This study aimed to understand the molecular characteristics of buffalo leukemia
      inhibitory factor (BuLIF) and the generation of a stably transfected COS-1_BuLIF
      cell line for its functional characterization. Cumulus cells, isolated from
      oocytes, were separated, and total cDNA was prepared. The BuLIF gene was ligated
      into the cloning vector pJET1.2/blunt and expression vector pAcGFP-N1 which was
      transfected into COS-1 cells and confirmed by qRT-PCR and Western blot. BuLIF was
      immunoprecipitated and evaluated through a MTT assay. qRT-PCR of STAT3 was
      performed. The multiple sequence alignment of BuLIF showed high similarity with
      sheep (98.77%) and cattle (96.62%) compared with other species. The BuLIF gene
      has an open reading frame of 609 nucleotides coding for 202 amino acids. BuLIF
      was integrated into the genome of COS-1 cells and resulted in the formation of
      dome-like secondary structures which are indicative of its functional role
      mediated through STAT3 proteins. In conclusion, this cell line is suitable for
      understanding LIF-mediated biological functions.

PMID- 28441663
TI  - Amygdalar Gray Matter Volume and Social Relating in Schizophrenia.
AB  - BACKGROUND: Poor social relating is a prominent feature of schizophrenia. The
      amygdala has been suggested as an important node in social brain networks.
      METHODS: By using structural magnetic resonance imaging, this study examined, for
      the first time, the relationship between amygdalar gray matter (GM) volume and
      social relating in 35 schizophrenia patients. Social anhedonia, interaction
      anxiety, extraversion, and sociable tendencies were assessed as indices of social
      relating. RESULTS: A correlation between GM volume in the amygdala and enhanced
      social relating was revealed. CONCLUSION: These findings indicate that volumetric
      decreases in the amygdala are related to impoverished sociability in
      schizophrenia.

PMID- 28441664
TI  - Protection against Legionnaire's Disease: Recombinant Flagellin A of Legionella
      pneumophila Can Induce Protective Immunity against Bacteremia in a BALB/c Murine
      Model.
AB  - To investigate the immunoprotective effects of the recombinant type A flagellin
      (FLA), the flaA gene of Legionella pneumophila serogroup 1 strain Paris was
      cloned into pET28a(+). Recombinant FLA (rFLA) was overexpressed in E. coli BL21
      (DE3) and purified by Ni2+ exchange chromatography. Female BALB/c aged 6-8 weeks
      were immunized with 20 MUg of rFLA. Nonimmunized mice along with mice inoculated
      with a sublethal dose of live L. pneumophila intravenously were considered as
      negative and positive controls, respectively. A significant serum antibody
      response was observed in female BALB/c mice immunized with rFLA. Production of
      IFN-gamma and IL-12, and TNF-alpha in the serum and the splenocyte cultures, and
      antigen-specific splenocyte proliferation suggested a strong innate and adaptive
      cell-mediated immunity response in rFLA-immunized mice. Intravenous lethal
      challenge with L. pneumophila serogroup 1 (strain Paris) showed that 60% of mice
      immunized with rFLA survived in a 10-day follow-up survey. These results show
      that rFLA from L. pneumophila can elicit strong innate and adaptive immune
      responses and suggest the possibility of a long-term immunity against lethal
      challenge with L. pneumophila.

PMID- 28441665
TI  - MicroRNA-1185 Promotes Arterial Stiffness though Modulating VCAM-1 and E-Selectin
      Expression.
AB  - BACKGROUND/AIMS: Atherosclerosis is the primary cause of cardiovascular ischaemic
      events; arterial stiffness is a characteristic of the atherosclerotic process.
      MicroRNAs (miRNAs) have been revealed as crucial modulators of atherosclerosis.
      However, the role of arterial stiffness-related miRNAs in the atherosclerotic
      process is still unclear. METHODS: Four hundred six participants from Northern
      China were enrolled in this study. Circulating miR-1185 and adhesion molecule
      levels were measured. Multiple linear regression models were used to evaluate the
      association of miR-1185 levels with brachial-ankle pulse wave velocity (baPWV)
      and adhesion molecule levels. A mediation analysis was also performed to examine
      the mediating effect. Cell adhesion molecule levels were measured in primary
      human umbilical vein endothelial cells (pHUVECs) and human umbilical vein smooth
      cells (HUVSMCs) transfected with miR-1185 or co-transfected with a miR-1185
      inhibitor. RESULTS: miR-1185 was independently correlated with arterial
      stiffness. A positive relationship between miR-1185 and vascular cell adhesion
      molecule-1 (VCAM-1) and E-selectin levels was observed. VCAM- 1 and E-selectin
      partially mediated the correlation between miR-1185 and arterial stiffness. miR
      1185 induced a significant increase in the VCAM-1 and E-selectin levels in
      pHUVECs and HUVSMCs in vitro. According to our mechanistic analysis, VCAM-1 and E
      selectin mediated miR-1185-induced arterial stiffening. CONCLUSIONS: miR-1185
      modulated the expression of VCAM-1 and E-selectin to promote arterial stiffening,
      suggesting that miR-1185 plays a crucial role in the development of
      atherosclerosis and may serve as a novel therapeutic target for atherosclerosis.

PMID- 28441666
TI  - A MicroRNA-124 Polymorphism is Associated with Fracture Healing via Modulating
      BMP6 Expression.
AB  - BACKGROUND: miR-124-3p has been reported to be involved in the pathogenesis of
      many diseases by modulating a variety of signaling pathways. In this study, we
      aimed to understand the impact of miR-124-3p expression level on the fracture
      healing in the patients of metaphyseal fracture of distal tibia, who received
      minimal invasive percutaneous plate osteosynthesis. METHODS: We firstly collected
      195 patients of metaphyseal fracture of distal tibia, and the genotype of
      rs531564 was determined: GG (n=124) and GC+CC (n=71). We collected information of
      the participants including age, gender, total in-hospital time, smoking and
      alcohol consumption. Subsequently, we searched the miRNA database online to
      identify the possible binding sequence of miR-124-3p located within the 3'-UTR of
      the target gene. We did correlation analysis and luciferase to understand the
      regulatory relationship between miR-124-3p and BMP6. Meanwhile, we also conducted
      real time PCR and western blotting analysis to study the mRNA and protein
      expression level of BMP6 in different genotype groups. We then treated the cells
      with scramble control, miR-124-3p mimics, BMP6 siRNA and miR-124-3p inhibitors to
      investigate the influence of miR-124-3p on the expression of BMP6, viability and
      apoptosis of cells. RESULTS: Total in-hospital time was significantly longer in
      GC+CC group than GG group. MiR-124-3p was up-regulated in GG group than GC and CC
      groups. BMP6 was virtual target of miR-124-3p. There existed negative regulatory
      relationship betweenmiR-124-3p and BMP6. The mRNA and protein expression level of
      BMP6 decreased in GG group. MiR-124-3p decreased the expression of BMP6. MiR-124
      3p negatively interfered with the viability of cells and BMP6 positively
      interfered with the viability of cells. MiR-124-3p reduced apoptosis and BMP6
      promoted apoptosis. CONCLUSION: These data proved the expression of miR-124-3p
      was associated with the healing of metaphyseal fracture of distal tibia, and
      could be recognized as a biomarker to predict the healing of metaphyseal fracture
      of distal tibia.

PMID- 28441667
TI  - Significance of User Participation in a Hospital Information System Success:
      Insights From a Case Study.
AB  - User participation in the development of a system is universally prescribed as an
      effective strategy to ensure the success of the resultant system. However, the
      existing literature on the merits of user participation only provides equivocal
      evidence. Various analyses of this literature point out that this equivocal
      evidence may be due to inconsistent operational measures of the user
      participation and system success constructs. Planned organizational change and
      participative decision making, the underlying paradigms of user participation
      construct, suggest that the development of some information systems may require
      blending of users' system-related functional expertise and developers' technical
      expertise to ensure system success. These paradigms also maintain that in case of
      well-defined, structured information systems user participation should enhance
      the likelihood of system success through better user understanding of the need
      for the system and system content and objectives, user trust, and a sense of
      system ownership. This research also described a case study involving the
      development and implementation of a medical records system for a neonatal
      intensive care unit in a large hospital in Texas. The case study provides
      evidence that in systems that require incorporation of user functional expertise
      user participation will enhance the likelihood of system success.

PMID- 28441668
TI  - Evaluation and management of orofacial pain.
AB  - Challenging to diagnose and manage, orofacial pain is a common and costly problem
      with a profound effect on quality of life. Delayed diagnosis and management can
      lead to prolonged patient suffering and disability. This article describes the
      background, assessment, differential diagnosis, management, and referral of
      patients with orofacial pain.

PMID- 28441670
TI  - Plaque erosion causing ST-segment elevation myocardial infarction: report of an
      optical coherence tomography-documented case and concise literature review.

PMID- 28441669
TI  - Keep them breathing: Cystic fibrosis pathophysiology, diagnosis, and treatment.
AB  - Cystic fibrosis (CF) affects more than 30,000 people in the United States and
      80,000 people worldwide. This life-threatening genetic disorder causes a buildup
      of thick, viscous mucus secretions in various organ systems, most commonly the
      gastrointestinal, pulmonary, and genitourinary systems. This article reviews the
      clinical manifestations, diagnosis, and monitoring of patients with CF as well as
      guidelines for management and emerging pharmacologic treatments.

PMID- 28441671
TI  - Swimming Upstream: Creating a Culture of High-Value Care.
AB  - As health system leaders strategize the best ways to encourage the transition
      toward value-based health care, the underlying culture-defined as a system of
      shared assumptions, values, beliefs, and norms existing within an environment
      continues to shape clinician practice patterns. The current prevailing medical
      culture contributes to overtesting, overtreatment, and health care waste.
      Choosing Wisely lists, appropriateness criteria, and guidelines codify best
      practices, but academic medicine as a whole must recognize that faculty and
      trainees are all largely still operating within the same cultural climate.
      Addressing this culture, on both local and national levels, is imperative for
      engaging clinicians in reforms and creating sustained changes that will deliver
      on the promise of better health care value. This Perspective outlines four steps
      for health system leaders to understand, cultivate, and maintain cultural changes
      toward value-based care: (1) Build the will for change through engaging frontline
      providers and communicating patient-centered motivations for health care value;
      (2) create necessary infrastructure to support value improvement efforts; (3)
      expose physicians to value-based payment structures; and (4) demonstrate
      leadership commitment and visibility to shared goals. The authors support their
      recommendations with concrete examples from emerging models and leaders across
      the country.

PMID- 28441672
TI  - How to Lead the Way Through Complexity, Constraint, and Uncertainty in Academic
      Health Science Centers.
AB  - Academic medicine is in an era of unprecedented and constant change due to
      fluctuating economies, globalization, emerging technologies, research, and
      professional and educational mandates. Consequently, academic health science
      centers (AHSCs) are facing new levels of complexity, constraint, and uncertainty.
      Currently, AHSC leaders work with competing academic and health service demands
      and are required to work with and are accountable to a diversity of stakeholders.
      Given the new challenges and emerging needs, the authors believe the leadership
      methods and approaches AHSCs have used in the past that led to successes will be
      insufficient. In this Article, the authors propose that AHSCs will require a
      unique combination of old and new leadership approaches specifically oriented to
      the unique complexity of the AHSC context. They initially describe the designer
      (or hierarchical) and heroic (military and transformational) approaches to
      leadership and how they have been applied in AHSCs. While these well-researched
      and traditional approaches have their strengths in certain contexts, the
      leadership field has recognized that they can also limit leaders' abilities to
      enable their organizations to be engaged, adaptable, and responsive.
      Consequently, some new approaches have emerged that are taking hold in academic
      work and professional practice. The authors highlight and explore some of these
      new approaches-the authentic, self, shared, and network approaches to leadership
      with attention to their application in and utility for the AHSC context.

PMID- 28441673
TI  - Gateways to the Laboratory: How an MD-PhD Program Increased the Number of
      Minority Physician-Scientists.
AB  - Traditional underrepresented minority (URM) groups (African Americans, Hispanic
      Americans, Native Americans) remain underrepresented among physician-scientists.
      To address the dearth of URM physician-scientists, in 1993 the Weill
      Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program developed a
      pipeline program, Gateways to the Laboratory (Gateways), which focuses on
      increasing the breadth and depth of the URM physician-scientist pipeline by
      offering an all-encompassing summer research training program which mirrors the
      life of a physician-scientist. This includes hypothesis-driven research and
      clinical shadowing opportunities, coupled with weekly career development
      workshops and extensive multitiered mentoring. Among the 245 alumni who had
      "graduated" from Gateways as of 2013, 88% have pursued or completed advanced
      degrees. Among these, 74% completed or are pursuing MD, PhD, or MD-PhD degrees;
      and 17% completed or are pursuing combined MD-PhD degrees, over one-third of whom
      are enrolled in the Tri-Institutional MD-PhD Program. Gateways outcomes are
      compared to other programs with similar missions, which shows that Gateways has
      been successful at preparing URMs for MD-PhD Programs. The program serves as a
      model for how to increase the national pool of competitive URM MD-PhD applicants.

PMID- 28441674
TI  - The Development of an Indigenous Health Curriculum for Medical Students.
AB  - Indigenous populations experience dramatic health disparities; yet, few medical
      schools equip students with the skills to address these inequities. At the
      University of Minnesota Medical School, Duluth campus, a project to develop an
      Indigenous health curriculum began in September 2013. This project used
      collaborative and decolonizing methods to gather ideas and opinions from multiple
      stakeholders, including students, community members, faculty, and administration,
      to guide the process of adding Indigenous health content to the curriculum to
      prepare students to work effectively with Indigenous populations. A mixed-methods
      needs assessment was implemented to inform the instructional design of the
      curriculum. In June 2014, stakeholders were invited to attend a retreat and
      complete a survey to understand their opinions of what should be included in the
      curriculum and in what way. Retreat feedback and survey responses indicated that
      the most important topics to include were cultural humility, Indigenous culture,
      social/political/economic determinants of health, and successful tribal health
      interventions. Stakeholders also emphasized that this content should be taught by
      tribal members, medical school faculty, and faculty in complementary departments
      (e.g., American Indian Studies, Education, Social Work) in a way that
      incorporates experiential learning.Preliminary outcomes include the addition of a
      seven-hour block of Indigenous content for first-year students taught primarily
      by Indigenous faculty from several departments. To address the systemic barriers
      to health and well-being and provider bias that Indigenous patients experience,
      this project sought to gather data and opinions regarding the training of medical
      students through a process of Indigenizing research and education.

PMID- 28441675
TI  - Teaching Today in the Practice Setting of the Future: Implementing Innovations in
      Graduate Medical Education.
AB  - PROBLEM: Implementing an innovation, such as offering new types of patient
      physician encounters through the patient-centered medical home (PCMH) model while
      maintaining Accreditation Council for Graduate Medical Education (ACGME)
      accreditation standards (e.g., patient encounter minimums for trainees), is
      challenging. APPROACH: In 2009, the Group Health Family Medicine Residency
      (GHFMR) received an ACGME Program Experimentation and Innovation Project (PEIP)
      exception that redefined the minimum Family Medicine Resident Review Committee
      requirement to 1,400 face-to-face visits and 250 electronic visits (1 electronic
      visit defined as 3 secure message or telephone encounters). The authors report
      GHFMR residents' continuity clinic encounters, specifically volume, from 2006
      through 2013 via pre- and post-PCMH implementation. They discuss the implications
      for leaders of high-performing practices who desire to innovate while maintaining
      accreditation. OUTCOMES: Post-PCMH residents had 20% more overall patient
      contact. The largest change in care delivery method included a large increase in
      secure messages between patients and residents. Pre-PCMH residents had more face
      to-face encounters; however, post-PCMH residents had more contact for all types
      of patient care encounters (face-to-face, secure messaging, and telephone) per
      hour of clinic time. NEXT STEPS: The ACGME PEIP exception, allowing the
      incorporation of the PCMH, facilitated an increase in patient access and immersed
      residents in primary care innovation (namely, practicing in a PCMH model during
      graduate medical education training). The next steps are to assess the effect of
      the PCMH on resident learning and clinical outcomes and to continue residents'
      access to training that keeps pace with today's health care delivery needs.

PMID- 28441676
TI  - Transitioning From Volume to Value: One Academic Medical Center's Approach to
      Improving Population Health.
AB  - PROBLEM: The U.S. health care system is undergoing a major transformation.
      Clinical delivery systems are now being paid according to the value of the care
      they provide, in accordance with the Triple Aim, which incorporates improving the
      quality and cost of care and the patient experience. Increasingly, financial risk
      is being transferred from insurers to clinical delivery systems that become
      responsible for both episode-based clinical care and the longitudinal care of
      patients. Thus, these delivery systems need to develop strategies to manage the
      health of populations. Academic medical centers (AMCs) serve a unique role in
      many markets yet may be ill prepared for this transformation. APPROACH: In 2013,
      Oregon Health & Science University (OHSU) partnered with a large health insurer
      and six other hospitals across the state to form Propel Health, a collaborative
      partnership designed to deliver the tools, methods, and support necessary for
      population health management. OHSU also developed new internal structures and
      transformed its business model to embrace this value-based care model. OUTCOMES:
      Each Propel Health partner included the employees and dependents enrolled in its
      employee medical plan, for approximately 55,000 covered individuals initially. By
      2017, Propel Health is expected to cover 110,000 individuals. Other outcomes to
      measure in the future include the quality and cost of care provided under this
      partnership. NEXT STEPS: Anticipated challenges to overcome include insufficient
      primary care networks, conflicting incentives, local competition, and the
      magnitude of the transformation. Still, the time is right for AMCs to commit to
      improving the health of populations.

PMID- 28441677
TI  - Building a Global, Online Community of Practice: The OPENPediatrics World Shared
      Practices Video Series.
AB  - PROBLEM: Health care professionals are familiar with engaging in local
      communities of practice (CoPs) within their hospital, region, and/or country, but
      despite the availability of online technologies that facilitate online global
      collaboration, the health care sector has yet to fully embrace these tools.
      APPROACH: In 2013, OPENPediatrics (an online social learning platform) launched
      the World Shared Practices video (WSP) series to engage and coalesce the global
      community of critical care clinicians. Each month, a 30- to 45-minute video
      featuring a pediatric critical care medicine expert, interspersed with questions
      for the audience, is released. Viewers contribute to the community discussion by
      leaving comments that display alongside the video. Clinicians are encouraged to
      asynchronously host an educational conference so they can watch the videos and
      participate in the discussion together. OUTCOMES: From March 2013-November 2015,
      28 WSPs were launched on a variety of topics. They were viewed over 18,414 times
      by 1,864 viewers in 132 countries and 760 hospitals; 1,155 comments were
      submitted. Attending physicians/consultants were the largest audience (36%
      [671/1,864]), and 37% (30/81) of responding viewers that commented in WSPs
      watched in small groups. The WSP series was reported to add value to respondents'
      learning or teaching and to have had a positive impact on their knowledge or
      practice. NEXT STEPS: Future research will focus on further describing the
      context and structure of the CoP and on more deeply investigating its higher
      level outcomes and impact. More work is needed to identify barriers and
      strategies that improve online community engagement.

PMID- 28441678
TI  - The Addiction Recovery Clinic: A Novel, Primary-Care-Based Approach to Teaching
      Addiction Medicine.
AB  - PROBLEM: Substance use is highly prevalent in the United States, but little time
      in the curriculum is devoted to training internal medicine residents in addiction
      medicine. APPROACH: In 2014, the authors developed and launched the Addiction
      Recovery Clinic (ARC) to address this educational gap while also providing
      outpatient clinical services to patients with substance use disorders. The ARC is
      embedded within the residency primary care practice and is staffed by three to
      four internal medicine residents, two board-certified addiction medicine
      specialists, one chief resident, and one psychologist. Residents spend one half
      day per week for four consecutive weeks at the ARC seeing new and returning
      patients. Services provided include pharmacological and behavioral treatments for
      opioid, alcohol, and other substance use disorders, with direct referral to local
      addiction treatment facilities as needed. Visit numbers, a patient satisfaction
      survey, and an end-of-rotation resident evaluation were used to assess the ARC.
      OUTCOMES: From 2014 to 2015, 611 patient encounters occurred, representing 97 new
      patients. Sixty-one (63%) patients were seen for opioid use disorder. According
      to patient satisfaction surveys, 29 (of 31; 94%) patients reported that the ARC
      probably or definitely helped them to cope with their substance use. Twenty-eight
      residents completed the end-of-rotation evaluation; all rated the rotation
      highly. NEXT STEPS: The ARC offers a unique primary-care-based approach to
      exposing internal medicine residents to the knowledge and skills necessary to
      diagnose, treat, and prevent unhealthy substance use. Future research will
      examine other clinical and educational outcomes.

PMID- 28441680
TI  - Magnetic Resonance Imaging Safety of Magnetically Controlled Growing Rods in an
      In Vivo Animal Model.
AB  - STUDY DESIGN: Experimental animal study. OBJECTIVE: To investigate the
      interaction between magnetically controlled growing rods (MCGRs) and magnetic
      resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: Growing rod treatment
      through serial operations results in adverse effects on the patient and high
      treatment costs. MCGRs can be lengthened noninvasively in an outpatient setting
      and with lower treatment costs. When MRI investigation is required, the
      interaction between MCGRs and MRI is an issue of concern in patients with MCGRs.
      This study investigated MRI compatibility of MCGRs in an in vivo setting.
      METHODS: The study was conducted on three sheep. A standard posterior approach
      was used. One polyaxial pedicle screw at the ends was placed. Two sheep were
      instrumented unilaterally and one bilaterally with MCGRs. Temperature change was
      measured using MR-compatible sensors. Thoracic and lumbar MRIs were obtained
      using a 0.3 T MRI unit. MRI waves were applied for 45 minutes and temperature
      changes were recorded every 3 minutes. The lengths of the MCGRs were measured and
      anteroposterior and lateral spine radiographs were obtained pre- and
      postoperatively. RESULTS: No displacement in the positions of the MCGRs occurred.
      The lengths of the MCGRs did not change compared with the preoperative length.
      The ability of the MCGRs to elongate was not impaired after MRI scanning. There
      was a mean increase in the temperature of the MCGRs by 1.45 degrees C (0.5-2.4
      degrees C). The MCGRs had a strong scattering effect on MRI of the related
      segments. CONCLUSION: This study indicated that lower magnet MRI is safe in an
      animal model with MCGRs, with no displacement of the rods and no changes in their
      length, no significant heating, and no adverse effects on the lengthening
      mechanism but with a significant scattering effect on visualization of the
      surrounding tissues. Further investigations are needed to clarify the exact
      distance where an MRI investigation of distant organs may be done without
      scattering. LEVEL OF EVIDENCE: N/A.

PMID- 28441679
TI  - The Drivers of Discretionary Utilization: Clinical History Versus Physician
      Supply.
AB  - PURPOSE: Because the effect of physician supply on utilization remains
      controversial, literature based on non-Medicare populations is sparse, and a
      physician supply expansion is under way, the potential for physician-induced
      demand across diverse populations is important to understand. A substantial
      proportion of gastrointestinal endoscopies may be inappropriate. The authors
      analyzed the impact of physician supply, practice patterns, and clinical history
      on esophagogastroduodenoscopy (EGD, defined as discretionary) among patients
      hospitalized with lower gastrointestinal bleeding (LGIB). METHOD: Among 34,344
      patients hospitalized for LGIB from 2004 to 2009, 43.1% and 21.3% had a
      colonoscopy or EGD, respectively, during the index hospitalization or within 6
      months after. Linking to the Dartmouth Atlas via patients' hospital referral
      region, gastroenterologist density and hospital care intensity (HCI) index were
      ascertained. Adjusting for age, gender, comorbidities, and race/education
      indicators, the association of gastroenterologist density, HCI index, and history
      of upper gastrointestinal disease with EGD was estimated using logistic
      regression. RESULTS: EGD was not associated with gastroenterologist density or
      HCI index, but was associated with a history of upper gastrointestinal disease
      (OR 2.30; 95% CI 2.17-2.43), peptic ulcer disease (OR 4.82; 95% CI 4.26-5.45),
      and liver disease (OR 1.34; 95% CI 1.18-1.54). CONCLUSIONS: Among patients
      hospitalized with LGIB, large variation in gastroenterologist density did not
      predict EGD, but relevant clinical history did, with association strengths
      commensurate with risk for upper gastrointestinal bleeding. In the scenario
      studied, no evidence was found that specialty physician supply increases will
      result in more discretionary care within commercially insured populations.

PMID- 28441681
TI  - Complications and Mortality Following One to Two-Level Anterior Cervical Fusion
      for Cervical Spondylosis in Patients Above 80 Years of Age.
AB  - STUDY DESIGN: A retrospective database review. OBJECTIVE: The aim of this study
      was to determine the complication and mortality rates in patients 80 years of age
      and older who were treated with anterior cervical fusion surgery and to compare
      these rates against those of other elderly patients. SUMMARY OF BACKGROUND DATA:
      Cervical spondylosis is frequently observed in the elderly and is the most common
      cause of myelopathy in older adults. With increasing life expectancies, a greater
      proportion of patients are being treated with spine surgery at a later age.
      Limited information is available regarding outcomes following anterior cervical
      fusion surgery in patients 80 years of age or older. METHODS: Medicare data from
      the PearlDiver Database (2005-2012) were queried for patients who underwent
      primary one to two-level anterior cervical spine fusion surgeries for cervical
      spondylosis. After excluding patients with prior spine metastasis, bone cancer,
      spine trauma, or spine infection, this cohort was divided into two study groups:
      patients 65 to 79 (51,808) and >=80 years old (5515) were selected. A cohort of
      matched control patients was selected from the 65 to 79-year-old and 90-day
      complication rates and 90-day and 1-year mortality rates were compared between
      cohorts. RESULTS: The proportion of patients experiencing at least one major
      medical complication was relatively increased by 53.4% in patients aged >=80
      years [odds ratio (OR) 1.63]. Patients 80 years of age or older were more likely
      to experience dysphagia (OR 2.16), reintubation (OR 2.34), and aspiration
      pneumonitis (OR 3.17). Both 90-day (OR: 4.34) and 1-year (OR 3.68) mortality were
      significantly higher in the >=80 year cohort. CONCLUSION: Patients 80 years of
      age or older are more likely to experience a major medical complication or
      mortality following anterior cervical fusion for cervical spondylosis than
      patients 65 to 79 years old. Dysphagia, aspiration pneumonitis, and reintubation
      rates are also significantly higher in patients 80 years of age or older.
      Although complication rates may be higher in this patient population, carefully
      selected patients could potentially derive much benefit from surgery and should
      not be screened out solely on the basis of age. LEVEL OF EVIDENCE: 4.

PMID- 28441682
TI  - Chondrosarcoma of the Osseous Spine: An Analysis of Epidemiology, Patient
      Outcomes, and Prognostic Factors Using the SEER Registry From 1973 to 2012.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To determine the epidemiology
      and prognostic indicators in patients with chondrosarcoma of the osseous spine.
      SUMMARY OF BACKGROUND DATA: Chondrosarcoma of the spine is rare, with limited
      data on its epidemiology, clinicopathologic features, and treatment outcomes.
      Therapy centers on complete en bloc resection with radiotherapy reserved for
      subtotal resection or advanced disease. METHODS: The Surveillance, Epidemiology,
      and End Results Registry was queried for patients with chondrosarcoma of the
      osseous spine from 1973 to 2012. Study variables included age, sex, race, year of
      diagnosis, size, grade, extent of disease, and treatment modality. RESULTS: The
      search identified 973 cases of spinal chondrosarcoma. Mean age at diagnosis was
      51.6 years, and 627% of patients were males. Surgical resection and radiotherapy
      were performed in 75.2% and 21.3% of cases, respectively. Kaplan-Meier analysis
      demonstrated overall survival (OS) and disease-specific survival (DSS) of 53% and
      64%, respectively, at 5 years. Multivariate Cox regression analysis showed that
      age (OS, P < 0.001; DSS, P = 0.007), grade (OS, P < 0.001; DSS, P < 0.001),
      surgical resection (OS, P < 0.001; DSS, P < 0.001), and extent of disease (OS, P
      < 0.001; DSS, P < 0.001) were independent survival determinants; tumor size was
      an independent predictor of OS (P = 0.006). For confined disease, age (P =
      0.013), decade of diagnosis (P = 0.023), and surgery (P = 0.017) were independent
      determinants of OS. For locally invasive disease, grade (OS, P < 0.001; DSS, P =
      0.003), surgery (OS, P = 0.013; DSS, P = 0.046), and size (OS, P = 0.001, DSS, P
      = 0.002) were independent determinants of OS and DSS. Radiotherapy was an
      independent indicator of worse OS for both confined (P = 0.004) and locally
      invasive disease (P = 0.002). For metastatic disease, grade (OS, P = 0.021; DSS,
      P = 0.012) and surgery (OS, P = 0.007; DSS, P = 0.004) were survival determinants
      for both OS and DSS, whereas radiotherapy predicted improved OS (P = 0.039).
      CONCLUSION: Surgical resection confers survival benefit in patients with
      chondrosarcoma of the spine independent of extent of disease. Radiotherapy
      improves survival in patients with metastatic disease and worsens outcomes in
      patients with confined and locally invasive disease. LEVEL OF EVIDENCE: 4.

PMID- 28441683
TI  - Geometric Torsion in Adolescent Idiopathic Scoliosis: A New Method to
      Differentiate Between Lenke 1 Subtypes.
AB  - STUDY DESIGN: Consecutive case series. OBJECTIVE: To study geometric torsion in
      thoracic adolescent idiopathic scoliosis (AIS) to propose it as a numerical three
      dimensional (3D) parameter that quantifies the scoliosis deformity. SUMMARY OF
      BACKGROUND DATA: AIS is a 3D deformity of the spine. The most widely accepted and
      used classification systems, however, still rely on two-dimensional aspects of x
      rays. Yet, a 3D classification of AIS remains elusive because there is no widely
      accepted 3D parameter in the clinical practice. METHODS: Analysis of 141 patients
      with Lenke type-1 deformity recruited in our institution. The Lenke
      classification was identified by two observers and 3D reconstructions were
      obtained using biplanar radiographs. Geometric torsion measuring the twisting
      effect of the spine was computed using a novel technique by approximating local
      arc lengths at the neutral vertebra in the thoracolumbar segment. An inter- and
      intragroup statistical analysis was performed to evaluate the torsion index, and
      how it relates to other 3D indices. RESULTS: A statistically significant increase
      in torsion was observed between Lenke 1A (1.15 mm) and Lenke 1C (2.10 mm)
      subgroups. No differences were found between the Lenke 1B (1.75 mm) subgroup with
      either of the other two subgroups. An automatic classification based on torsion
      indices identified two groups: one with high torsion values (3.02 mm) and one
      with low torsion values (0.82 mm). Statistically significant differences were
      found between the main thoracic planes of maximum curvature (PMC) orientation of
      the high-torsion group (73.72 degrees ) and the low-torsion group (79.85 degrees
      ). Statistically significant differences were also found for the
      thoracolumbar/lumbar PMC orientation between the high-torsion group (56.41
      degrees ) and the low-torsion group (49.25 degrees ). CONCLUSION: These results
      suggest that a numerical method of describing scoliosis in 3D is within reach.
      They also suggest the existence of two subgroups of 3D deformations based on
      torsion values (high and low) with links to PMC orientation. LEVEL OF EVIDENCE:
      4.

PMID- 28441684
TI  - Development of Consensus-Based Best Practice Guidelines for Postoperative Care
      Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.
AB  - STUDY DESIGN: Delphi process with multiple iterative rounds using a nominal group
      technique. OBJECTIVE: The aim of this study was to use expert opinion to achieve
      consensus on various aspects of postoperative care following posterior spinal
      fusion (PSF) for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND
      DATA: Significant variability exists in postoperative care following PSF for AIS,
      despite a relatively healthy patient population and continuously improving
      operative techniques. Current practice appears based either on lesser quality
      studies or the perpetuation of long-standing protocols. METHODS: An expert panel
      composed of 26 pediatric spine surgeons was selected. Using the Delphi process
      and iterative rounds using a nominal group technique, participants in this panel
      were presented with a detailed literature review and asked to voice opinion
      collectively during three rounds of voting (one electronic and two face-to-face).
      Agreement >80% was considered consensus. Interventions without consensus were
      discussed and revised, if feasible. RESULTS: Consensus was reached to support 19
      best practice guideline (BPG) measures for postoperative care addressing non-ICU
      admission, perioperative pain control, dietary management, physical therapy,
      postoperative radiographs, surgical bandage management, and indications for
      discharge. CONCLUSION: We present a consensus-based BPG consisting of 19
      recommendations for the postoperative management of patients following PSF for
      AIS. This can serve to reduce variability in practice in this area, help develop
      hospital specific protocols, and guide future research. LEVEL OF EVIDENCE: 5.

PMID- 28441685
TI  - Stagnant Physical Therapy Referral Rates Alongside Rising Opioid Prescription
      Rates in Patients With Low Back Pain in the United States 1997-2010.
AB  - STUDY DESIGN: A cross-sectional observational study utilizing the National
      Ambulatory and National Hospital Ambulatory Medical Care Surveys between 1997 and
      2010. OBJECTIVE: The aim of this study was to characterize national physical
      therapy (PT) referral trends during primary care provider (PCP) visits in the
      United States. SUMMARY OF BACKGROUND DATA: Despite guidelines recommending PT for
      the initial management of low back pain (LBP), national PT referral rates remain
      low. METHODS: Race, ethnicity, age, payer type, and PT referral rates were
      collected for patients aged 16 to 90 years who were visiting their PCPs.
      Associations among demographic variables and PT referral were determined using
      logistic regression. RESULTS: Between 1997 and 2010, we estimated 170 million
      visits for LBP leading to 17.1 million PT referrals. Average proportion of PCP
      visits associated with PT referrals remained stable at about 10.1% [odds ratio
      (OR) 1.00, 95% confidence interval (95% CI) 0.96-1.04)], despite our prior
      finding of increasing number of visits associated with opioid prescriptions in
      the same timeframe.Lower PT referral rates were observed among visits by patients
      who were insured by Medicaid (OR 0.48, 95% CI 0.33-0.69) and Medicare (OR 0.50,
      95% CI 0.35-0.72). Furthermore, visits not associated with PT referrals were more
      likely to be associated with opioid prescriptions (OR 1.69, 95% CI 1.22-2.35).
      CONCLUSION: Although therapies delivered by PTs are promoted as a first-line
      treatment for LBP, PT referral rates remain low. There also exist disparately
      lower referral rates in populations with more restrictive health plans and
      simultaneous opioid prescription. Our findings provide a broad overview to PT
      prescription trend and isolate concerning associations requiring further
      explorations. LEVEL OF EVIDENCE: 3.

PMID- 28441686
TI  - Surgical and Functional Outcomes After Multilevel Cervical Fusion for
      Degenerative Disc Disease Compared With Fusion for Radiculopathy: A Study of
      Workers' Compensation Population.
AB  - STUDY DESIGN: Retrospective cohort comparative study. OBJECTIVE: To evaluate
      presurgical and surgical factors that affect return to work (RTW) status after
      multilevel cervical fusion, and to compare outcomes after multilevel cervical
      fusion for degenerative disc disease (DDD) versus radiculopathy. SUMMARY OF
      BACKGROUND DATA: Cervical fusion provides more than 90% of symptomatic relief for
      radiculopathy and myelopathy. However, cervical fusion for DDD without
      radiculopathy is considered controversial. In addition, multilevel fusion is
      associated with poorer surgical outcomes with increased levels fused. METHODS:
      Data of cervical comorbidities was collected from Ohio Bureau of Workers'
      Compensation for subjects with work-related injuries. The study population
      included subjects who underwent multilevel cervical fusion. Patients with
      radiculopathy or DDD were identified. Multivariate logistic regression was
      performed to identify factors that affect RTW status. Surgical and functional
      outcomes were compared between groups. RESULTS: Stable RTW status within 3 years
      after multilevel cervical fusion was negatively affected by: fusion for DDD, age
      > 55 years, preoperative opioid use, initial psychological evaluation before
      surgery, injury-to-surgery > 2 years and instrumentation.DDD group had lower rate
      of achieving stable RTW status (P= 0.0001) and RTW within 1 year of surgery (P=
      0.0003) compared with radiculopathy group. DDD patients were less likely to have
      a stable RTW status [odds ratio, OR = 0.63 (0.50-0.79)] or RTW within 1 year
      after surgery [OR = 0.65 (0.52-0.82)].DDD group had higher rate of opioid use (P=
      0.001), and higher rate of disability after surgery (P= 0.002). CONCLUSION:
      Multiple detriments affect stable RTW status after multilevel cervical fusion
      including DDD. DDD without radiculopathy was associated with lower RTW rates,
      less likelihood to return to work, higher disability, and higher opioid use after
      surgery. Multilevel cervical fusion for DDD may be counterproductive. Future
      studies should investigate further treatment options of DDD, and optimize patient
      selection criteria for surgical intervention. LEVEL OF EVIDENCE: 3.

PMID- 28441687
TI  - C-arm Positioning Is a Significant Source of Radiation in Spine Surgery.
AB  - STUDY DESIGN: Prospective chart review. OBJECTIVE: It is well-known that
      radiation exposure during minimally invasive spine procedures can be substantial.
      Less interest has focused on setup radiation exposure before incision, including
      preoperative images used for surgical approach. The present study seeks to better
      quantify the significance of setup radiation in the total radiation exposure of
      minimally invasive spine surgery. SUMMARY OF BACKGROUND DATA: Radiographic
      localization is necessary in minimally invasive spine procedures to visualize
      anatomy, but increased radiation exposure is associated with health risks.
      Preoperative imaging for anatomical localization has not been previously analyzed
      as an appreciable source of radiation. METHODS: From an institutional review
      board-approved database of more than 1100 procedures, the minimally invasive
      spine cases with recorded set-up radiation were extracted. The total radiation,
      set-up radiation, and procedure type data were evaluated. Statistics were
      generated using a chi-squared analysis. RESULTS: Set-up and total radiation data
      were collected for 270 spine surgeries performed by four surgeons at two
      locations. There were 30 thoracic and 240 thoracolumbar/lumbar cases; 78 anterior
      and 192 posterior cases. Average total radiation (set-up and intraoperative) was
      8.04 rad, and average setup radiation was 1.90 rad (28%, std 2.97 rad) across all
      cases. On average for the thoracolumbar/lumbar cases, set-up radiation accounted
      for almost 25% of total radiation with 1.76 rad from setup out of 8.16 rad total.
      Thoracic-only cases often necessitated even more images for localization,
      generating an average set-up/total percentage of 52%. Across all procedures, set
      up radiation significantly increased the total radiation exposure because it
      accounted for more than 25% of the total procedure. CONCLUSION: Radiation
      exposure during preoperative localization can be substantial. Operating room
      personnel should recognize the high percentage of radiation that occurs during
      set-up, and merit should be given to techniques and technologies that can limit
      unnecessary radiation exposure during this portion of the procedure. LEVEL OF
      EVIDENCE: 2.

PMID- 28441688
TI  - Magnetic Controlled Growing Rods as a Treatment of Early Onset Scoliosis: Early
      Results With Two Patients: Erratum.

PMID- 28441689
TI  - Coeliac disease: further evidence that biopsy is not always necessary for
      diagnosis.
AB  - OBJECTIVES: Growing evidence supports the view that the diagnosis of coeliac
      disease (CD) can be made by serological tests alone, although this approach is
      still not widely accepted. We previously showed in retrospective and prospective
      studies that in adults an IgA-tissue transglutaminase antibody cut-off can be
      defined above which the positive predictive value for CD is 100%. Following a
      change in the analytical method for measuring the antibody, our objectives were
      to re-examine this finding in a larger series of adults to ascertain whether a
      diagnosis of CD can be reliably made in a proportion of patients without the need
      for small bowel biopsy and to re-evaluate the diagnostic guidelines used in our
      centre. PATIENTS AND METHODS: A retrospective analysis was done in an unselected
      series of 270 adult patients who had small bowel biopsies and serum IgA-tissue
      transglutaminase antibody levels measured from 2009 to 2014. RESULTS: At an IgA
      tissue transglutaminase antibody cut-off greater than 45 U/ml (>8*upper limit of
      normal+2SDs) the positive predictive value for CD in this cohort was 100%; 40% of
      cases were above this cut-off. CONCLUSION: We have verified that a diagnosis of
      CD can be reliably made in a high proportion of adults based on serology alone
      using the IgA-tissue transglutaminase antibody method specified. These results
      add to the body of evidence that small bowel biopsy should no longer be
      considered mandatory for the diagnosis of CD. On the basis of these results the
      diagnostic guidelines in our centre have been modified.

PMID- 28441690
TI  - The postoperative Model for End stage Liver Disease score as a predictor of short
      term outcome after transplantation of extended criteria donor livers.
AB  - BACKGROUND: Recently, the postoperative Model for End stage Liver Disease score
      (POPMELD) was suggested as a definition of postoperative graft dysfunction and a
      predictor of outcome after liver transplantation (LT). AIM: The aim of the
      present study was to validate this concept in the context of extended criteria
      donor (ECD) organs. PATIENTS AND METHODS: Single-center prospectively collected
      data (OPAL study/01/11-12/13) of 116 ECD LTs were utilized. For each recipient,
      the Model for End stage Liver Disease (MELD) score was calculated for 7
      postoperative days (PODs). The ability of international normalized ratio,
      bilirubin, aspartate aminotransferase, Donor Risk Index, a recent definition of
      early allograft dysfunction, and the POPMELD was compared to predict 90-day graft
      loss. Predictive abilities were compared by receiver operating characteristic
      curves, sensitivity and specificity, and positive and negative predictive values.
      RESULTS: The median Donor Risk Index was 1.8. In all, 60.3% of recipients were
      men [median age of 54 (23-68) years]. The median POD1-7 peak-aspartate
      aminotransferase value was 1052 (194-17 577) U/l. The rate of early allograft
      dysfunction was 22.4%. The 90-day graft survival was 89.7%. Out of possible
      predictors of the 90-day graft loss MELD on POD5 was the best predictor of
      outcome (area under the curve=0.84). A MELD score of 16 or more on POD5 predicted
      the 90-day graft loss with a specificity of 80.8%, a sensitivity of 81.8%, and a
      positive and negative predictive value of 31 and 97.7%. CONCLUSION: A MELD score
      of 16 or more on POD5 is an excellent predictor of outcome in ECD donor LT.
      Routine evaluation of POPMELD scores might support clinical decision-making and
      should be reported routinely in clinical trials.

PMID- 28441691
TI  - The shorter the person, the higher the blood pressure: a birth cohort study.
AB  - OBJECTIVE: Short adult stature is known to be associated with increased
      cardiovascular morbidity and mortality, but the underlying explanatory mechanisms
      remain largely unknown. The purpose of the current study was to evaluate the
      relationship between height and blood pressure (BP), a major determinant of
      cardiovascular disease (CVD). METHODS: We performed BP measurements including 24
      h ambulatory BP measurements in 534 participants (mean age 61 +/- 3 years, 51.3%
      women) from the Helsinki Birth Cohort Study. None of the study participants had
      medication affecting vasculature or BP. We assessed the influence of height on
      CVD risk factors with a standardized z-score representing the difference from the
      mean value for the whole study cohort. RESULTS: Daytime SBP, pulse pressure, and
      mean arterial pressure showed significant inverse associations with height
      (adjusted for age, leisure-time physical activity, body fat percentage, and
      smoking). Height was by itself a strong determinant of pulse pressure
      independently of BMI. In addition, total cholesterol, triglycerides, and
      apolipoprotein B concentrations decreased with increasing height. CONCLUSION:
      Shorter individuals have higher BP levels than taller individuals. This may at
      least partly explain the inverse association between height and CVD. In normal
      weight and slightly overweight individuals, the relationship between BP and
      height is independent of BMI and adiposity.

PMID- 28441692
TI  - Physiological role of endothelin-1 in flow-mediated vasodilatation in humans and
      impact of cardiovascular risk factors.
AB  - OBJECTIVES: The current study addressed the hypothesis that the local decrease in
      endothelin-1 (ET-1) bioavailability during sustained flow increases contributes
      to endothelium-dependent, flow-mediated dilatation (FMD) of conduit arteries and
      is altered in presence of cardiovascular risk factors. METHODS AND RESULTS: In
      nine young healthy individuals, the decrease in local ET-1 plasma levels and
      radial artery FMD in response to hand skin heating (from 34 to 44  degrees C) was
      not affected by endothelin type A (ETA) receptor blockade, achieved using the
      brachial infusion of BQ-123 (100 nmol/min per l of forearm), as compared with
      physiological saline (0.9% NaCl) infusion. In contrast, endothelin type B (ETB)
      receptor blockade with BQ-788 (10 nmol/min per l) suppressed the decrease in
      plasma ET-1 during heating and reduced FMD, without altering nitric oxide
      release. The coinfusion of BQ-123 did not affect the inhibitory effect of ETB
      receptor blockade on the decrease in ET-1 plasma levels during heating but
      prevented the reduction in FMD. Basal radial artery parameters, systemic
      hemodynamics, and endothelium-independent dilatation to glyceryl trinitrate were
      not modified by ETA and/or ETB blockade. In a general population of 40
      participants without treatment or major cardiovascular diseases, including the
      nine healthy individuals, the reduction in endothelin-1 level during heating was
      correlated with FMD (r = -0.55, P < 0.001) and decreased with increased age (r =
      0.49, P = 0.001), mean arterial blood pressure (r = 0.48, P = 0.002), and total
      cholesterol level (r = 0.37, P = 0.024). CONCLUSION: The uptake of endothelin-1
      by ETB receptors contributes to conduit artery FMD, preventing its
      vasoconstrictor action mediated by ETA receptors. The alteration of this
      mechanism by cardiovascular risk factors may contribute to endothelial
      dysfunction.

PMID- 28441693
TI  - Sex differences in fat distribution influence the association between BMI and
      arterial stiffness.
AB  - CONTEXT AND OBJECTIVE: The increase in arterial stiffness in patients with the
      metabolic syndrome is strongly related to the amount of visceral adipose tissue.
      In clinical practice, anthropometric measurements such as BMI and waist
      circumference are commonly used to assess general and abdominal adiposity. Waist
      circumference is a composite measure of subcutaneous and visceral abdominal
      adipose tissue. As the distribution of intra-abdominal fat differs between men
      and women, we investigated the sex-specific associations between different
      anthropometric measures for general and abdominal obesity with arterial
      stiffness. METHODS: A cross-sectional descriptive study was performed in 1517
      participants of the Nijmegen Biomedical Study, aged 50-70 years. After
      measurement of height, waist circumference and hip circumference, the following
      indices were calculated: BMI, waist-hip ratio and waist-height ratio (WHtR).
      Arterial stiffness was assessed by measurement of carotid-femoral pulse wave
      velocity (PWV). The association between the anthropometric indices and vascular
      stiffness was investigated by linear regression analysis adjusting for the
      traditional cardiovascular risk factors. RESULTS: BMI, waist circumference, waist
      hip ratio and WHtR correlated positively with PWV in univariate analysis both in
      men and women (all P < 0.016). Hip circumference was only associated with PWV in
      women (P < 0.001). After adjustment for age and heart rate, waist circumference
      and WHtR (standardized beta of 0.142 and 0.141, respectively, both P < 0.001)
      showed the strongest associations with PWV in men, whereas in women only BMI was
      associated with PWV (standardized beta of 0.177, P < 0.001). In men, WHtR was
      independently related to increased arterial stiffness, after adjustment for BMI
      and traditional cardiovascular risk factors. In women, in multivariate analyses,
      BMI remained significantly positively associated with PWV, whereas WHtR became
      negatively associated with PWV. CONCLUSION: Sex-related differences in adipose
      tissue distribution influence the association between anthropometric measures of
      obesity and vascular stiffness as measured with by PWV. We found that in men,
      WHtR showed the strongest association with PWV, whereas in women BMI was best
      associated with a higher PWV.

PMID- 28441694
TI  - Arterial stiffness is increased in nondiabetic, nonhypertensive postmenopausal
      women with nonalcoholic fatty liver disease.
AB  - OBJECTIVES: The purpose of this study was to assess the relationship between
      nonalcoholic fatty liver disease (NAFLD) and arterial stiffness in nondiabetic,
      nonhypertensive postmenopausal women with and without metabolic syndrome.
      METHODS: We divided 1007 postmenopausal women into two groups (NAFLD and
      controls) and then three groups (NAFLD with metabolic syndrome, NAFLD without
      metabolic syndrome, and controls), respectively. To exclude the influence of
      confounding factors, we studied a specifically selected group with no additional
      cardiovascular risk. Carotid intima-media thickness (CIMT), carotid-femoral pulse
      wave velocity (cf-PWV), and flow-mediated dilatation (FMD) were measured in all
      study patients and controls. RESULTS: Patients with NAFLD had significantly
      greater CIMT than did controls (P < 0.001). cf-PWV was also significantly higher
      in patients with NAFLD than in controls (P < 0.001). We found significantly
      decreased FMD in patients with NAFLD than in control patients (P < 0.001).
      Although patients with NAFLD and metabolic syndrome had greater CIMT and cf-PWV
      and less FMD than healthy patients did (P < 0.05), there were no significant
      differences in CIMT, cf-PWV, and FMD (P > 0.05) between patients with NAFLD with
      and without metabolic syndrome. CONCLUSION: The presence of NAFLD is associated
      with an increased risk of arterial stiffness in postmenopausal women, independent
      of the presence of metabolic syndrome.

PMID- 28441695
TI  - Increased high-risk coronary plaque burden is associated with arterial stiffness
      in patients with type 2 diabetes without clinical signs of coronary artery
      disease: a computed tomography angiography study.
AB  - OBJECTIVES: Arterial stiffness and subclinical coronary atherosclerosis may yield
      valuable information on cardiovascular risk. We aimed to characterize coronary
      atherosclerosis in asymptomatic patients with type 2 diabetes and healthy
      controls and to investigate the association between baseline arterial stiffness
      and coronary plaque volumes after 5-year follow-up. METHODS: Data from 45
      patients and 61 matched controls were available for coronary plaque assessment.
      For analysis including carotid-femoral pulse wave velocity (PWV), 43 patients and
      55 controls were available. At follow-up, mean (SD) age of participants was 63 +/
      10 years, and mean diabetes duration (SD) in the patient group was 7.8 +/- 1.4
      years. Arterial stiffness (PWV) was assessed by tonometry at both visits. Total,
      calcified, noncalcified, low-density noncalcified coronary plaques volumes and
      other plaque characteristics were assessed by coronary computed tomography
      angiography at follow-up. RESULTS: Despite of similar or better blood pressure
      and plasma lipid control, patients had, compared with controls, a higher number
      of plaques with spotty calcifications (P < 0.01) and remodeling index more than
      1.1 (P < 0.05), larger calcified plaque volumes [patients vs. CONTROLS: 11 (0-65)
      vs. 3 (0-30) MUl (P = 0.03)] and higher PWV [patients vs. controls at baseline:
      9.1 +/- 2.2 vs. 7.9 +/- 1.4 m/s (P < 0.01), at follow-up: 9.3 +/- 2.3 vs. 8.4 +/-
      1.8 m/s (P = 0.02)]. Baseline PWV was associated with volumes of all plaque types
      in crude analysis (P < 0.01) and with low-density noncalcified plaque volume in
      analysis adjusted for age, sex, diabetes and blood pressure (P = 0.01).
      CONCLUSION: Coronary plaques with unfavorable characteristics are more prevalent
      in well controlled asymptomatic patients with type 2 diabetes compared with
      healthy controls and independently associated with arterial stiffness.Clinical
      trials registration number: NCT02001532.

PMID- 28441697
TI  - Hypertension management in a population of older adults in rural South Africa.
AB  - OBJECTIVE: Assess awareness, treatment, and control of hypertension, as an
      indication of its management, in rural South Africa, especially regarding
      modifiers of these variables. METHODS: A population-representative sample of
      adults aged at least 40 years residing in the rural Agincourt subdistrict
      (Mpumalanga Province) covered by a long-term health and sociodemographic
      surveillance system was recruited. In-person interviews, physical exams, and
      dried blood spots were collected. Hypertension awareness, treatment, and control
      rates were assessed. A regression model was built to identify predictors of those
      outcomes. RESULTS: The mean age of the 2884 hypertensive participants was 64.1 +/
      12.7 years. Hypertension awareness rate was 64.4%, treatment among those aware
      was 89.3 and 45.8% of those treated were controlled. Considering aware and
      unaware hypertensives, treatment rate was 49.7% and control 22.8%. In the
      multivariable regression model, awareness was predicted by female sex, age at
      least 60 years, higher social economic status, prior cardiovascular disease
      (CVD), nonimmigrant status, literacy, and physical limitation. Improved control
      among those treated was predicted by age at least 60 years. Blood pressure
      control among all hypertensive study participants was predicted by female sex,
      being HIV-negative, age at least 60 years, nonimmigrant status, and prior CVD.
      CONCLUSION: High rates of awareness and treatment of hypertension as well as good
      levels of control were found in this population, probably explained by the long
      term surveillance program conducted in the area. Considering the predictors of
      hypertension management, particular attention should be given to men, residents
      younger than 60 years, immigrants, and study participants without CVD as these
      characteristics were predictors of poor outcome.

PMID- 28441696
TI  - Declining blood pressure and intensification of blood pressure management among
      people over 80 years: cohort study using electronic health records.
AB  - BACKGROUND: Management of high blood pressure (BP) in people over 80 years is
      controversial, but there is limited information available concerning the uptake
      of hypertension treatment at this age. OBJECTIVE: To evaluate use of
      antihypertensive drugs and changes in SBP and DBP from 2001 to 2014 in men and
      women aged 80 years and over. METHODS: Cohort study using primary care electronic
      health records of 265 225 participants from the UK Clinical Practice Research
      Datalink. Records of BP and antihypertensive medications were analysed. Linear
      trends were estimated by frailty category in multiple regression models. RESULTS:
      Data were analysed for 116 401 men and 148 824 women. The proportion with BP
      recorded increased from 51% in 2001 to 78% in 2014. The proportion of patients
      prescribed antihypertensive medications increased from 64 to 76%. Mean SBP
      declined from 150 (SD 20) mmHg in 2001 to 135 (16) mmHg in 2014. In 'fit'
      participants, the decline in SBP was 12.4 (95% confidence interval 11.9-13.0)
      mmHg/decade in those treated for hypertension and 8.5 (7.8-9.1) mmHg in those not
      treated. The decline in SBP was smaller as frailty increased. The proportion of
      all participants with BP less than 140/90 mmHg increased from 14 to 44% in the
      study period. CONCLUSION: In octogenarians, BP treatment has intensified between
      2001 and 2014. BP values have declined in both treated and untreated
      participants, with a substantial increase in the proportion achieving
      conventional BP targets.

PMID- 28441698
TI  - Ambulatory arterial stiffness index and its role in assessing arterial stiffness
      in dialysis patients.
AB  - OBJECTIVE: Ambulatory arterial stiffness index (AASI) is a parameter derived from
      ambulatory blood pressure (ABP) readings. It is calculated as 1 minus the linear
      slope of DBP on SBP. We tested its value in assessing arterial stiffness in
      dialysis patients. METHODS: We performed a cross-sectional analysis of the
      baseline data from a cohort study. A total of 344 patients on maintenance
      hemodialysis from six tertiary hospitals were included. All patients underwent
      ABP monitoring and carotid-femoral pulse wave velocity (cfPWV) measurement.
      Clinical determinants of AASI were analyzed, and the ability of AASI for
      assessing arterial stiffness was compared with ambulatory pulse pressure (PP).
      RESULTS: Multiple regression analysis revealed that ambulatory PP (beta = 0.003),
      current smoker (beta = -0.069), age (beta = 0.003) and ambulatory SBP (beta =
      0.001) were independent determinants of AASI. Ambulatory PP correlates better
      with cfPWV than AASI (r = 0.28 for AASI and 0.59 for PP; P for difference:
      <0.001). When cfPWV was treated as a categorical variable, receiver operating
      characteristic curve analysis also showed a more potent predictive value of PP
      over AASI (area under the curve: 0.64 for AASI, 0.80 for PP; P for difference:
      <0.001). Net reclassification improvement and integrated discrimination
      improvement analysis demonstrated no added predictive value of AASI to PP (net
      reclassification improvement = -2.2%, P = 0.26; integrated discrimination
      improvement = 0.001, P = 0.51). Sensitivity analysis in patients with more ABP
      readings (>=49) yielded similar results. CONCLUSION: For dialysis patients, AASI
      has very limited value in assessing arterial stiffness, whether used alone or
      added to PP. Our results suggest that this index should not be used as a
      surrogate marker of arterial stiffness for dialysis patients in future practice
      and studies.

PMID- 28441699
TI  - Folic acid therapy reduces the risk of mortality associated with heavy
      proteinuria among hypertensive patients.
AB  - OBJECTIVE: We aimed to evaluate whether proteinuria and estimated glomerular
      filtration rate (eGFR) levels can modify the efficacy of folic acid therapy on
      the risk of all-cause mortality among hypertensive patients in the China Stroke
      Primary Prevention Trial, a randomized, double-blind, and controlled trial.
      METHODS: A total of 20 702 hypertensive patients without a history of major
      cardiovascular diseases were randomly assigned to a double-blind daily treatment
      of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n = 10 348),
      or 10-mg enalapril alone (n = 10 354). All-cause mortality, a prespecified
      endpoint of the China Stroke Primary Prevention Trial, was the main outcome in
      this analysis. RESULTS: Over a median treatment duration of 4.5 years, in the
      enalapril alone group, both heavy proteinuria [vs. absent, 10.8 vs. 2.7%; hazard
      ratio = 3.30; 95% confidence interval (CI): 2.10-5.18] and lower eGFR levels (<60
      vs. >=90 ml/min per 1.73 m, 13.0 vs. 2.2%; hazard ratio = 1.93; 95% CI: 1.19
      3.12) were significantly associated with increased risk of all-cause mortality.
      Folic acid supplementation significantly reduced the risk of all-cause mortality
      in patients with heavy proteinuria (6.4% in the enalapril-folic acid vs. 10.8% in
      the enalapril alone group, hazard ratio = 0.49; 95% CI: 0.26-0.94), but not in
      those with absent or mild proteinuria (2.8 vs. 2.9%, hazard ratio = 0.99; 95% CI:
      0.84-1.17; P for interaction = 0.040). However, eGFR levels did not significantly
      modify the effect of folic acid supplementation in reducing the risk of all-cause
      mortality (P for interaction = 0.228). CONCLUSION: Among hypertensive patients
      without a history of major cardiovascular diseases, folic acid therapy could
      reduce the mortality risk associated with heavy proteinuria.

PMID- 28441700
TI  - Ultrasound-based renal sympathetic denervation for the treatment of therapy
      resistant hypertension: a single-center experience.
AB  - INTRODUCTION: The effectiveness of renal sympathetic denervation (RDN) as a
      treatment for therapy-resistant hypertension has been doubted as the Simplicity
      HTN-3 trial was unable to show any treatment benefit over sham procedure. This
      might partly be explained by a high procedural variability in treatment with
      radiofrequency-based catheters. Recently, newer systems for RDN, like ultrasound
      based devices, have been introduced into practice. To date however, data on their
      effectiveness for the treatment of resistant hypertension are scarce. We sought
      to evaluate the safety and effectiveness of an ultrasound-based, balloon
      irrigated RDN catheter in a larger single-center cohort. METHODS: Patients with
      therapy-resistant hypertension [average blood pressure (BP) >135 mmHg SBP or >90
      mmHg DBP in ambulatory BP measurement despite at least three antihypertensive
      drugs, including at least one diuretic] underwent ultrasound-based RDN. Treatment
      effect was assessed by comparing BP values at baseline and 3 months after the
      procedure. Patients underwent renal artery duplex sonography or MRI before and
      after RDN to exclude renal artery stenosis. RESULTS: Fifty consecutive patients
      underwent ultrasound-based RDN, of which 25 had undergone an unsuccessful
      radiofrequency RDN before. Mean SBP change at 3 months was -9.7 +/- 12.6/-10.6 +/
      13.7/-8.2 +/- 15.2 mmHg (ambulatory 24-h mean/daytime/night, P < 0.001 for all)
      and DBP changed by -5.1 +/- 7.4/-5.8 +/- 7.8/-3.9 +/- 10.3 mmHg (P <=
      0.001/<0.001/0.01). No new renal artery stenosis could be detected after RDN.
      CONCLUSION: Ultrasound-based RDN seems to be well tolerated and effective for the
      treatment of patients with therapy-resistant hypertension.

PMID- 28441701
TI  - The Market for Blood.

PMID- 28441702
TI  - Pricing in the Market for Anticancer Drugs.

PMID- 28441703
TI  - In Vitro and In Vivo Inhibitory Effects of alpha-Mangostin on Cholangiocarcinoma
      Cells and Allografts
AB  - We investigated the anti-cholangiocarcinoma effect of alpha-mangostin from
      Garcinia mangostana pericarp extract(GM) in a human cholangiocarcinoma (CCA) cell
      line and a hamster CCA allograft model. In vitro, human CCA cellswere treated
      with GM at various concentrations and for different time periods; then cell-cycle
      arrest and apoptosiswere evaluated using flow cytometry, and metastatic potential
      with wound healing assays. In vivo, hamster allograftswere treated with GM,
      gemcitabine (positive control) and a placebo (negative control) for 1 month;
      tumor weight andvolume were then determined. Histopathological features and
      immunostaining (CK19 and PCNA) characteristics wereexamined by microscopy. The
      present study found that alpha-mangostin could: inhibit CCA cell proliferation by
      inducingapoptosis through the mitochondrial pathway; induce G1 cell-cycle arrest;
      and inhibit metastasis. Moreover, alpha-mangostincould inhibit CCA growth, i.e.
      reduce tumor mass (weight and size) and alter CCA pathology, as evidenced by
      reducedpositive staining for CK19 and PCNA. The present study thus suggested that
      alpha-mangostin is a promising anti-CCAcompound whose ready availability in
      tropical countries might indicate use for prevention and treatment of CCA.

PMID- 28441704
TI  - A Study of Alcohol Consumption and Obesity as Main Risk Factor for Symptomatic
      Gallbladder Stone: a Case-Control Study
AB  - Background: Gallbladder stone (GBS) is a common gastrointestinal disease that can
      progress to severe cholecystitisand is a strong risk factor for gallbladder
      cancer (GBC). The present study was conducted to evaluate region-specificcauses
      of GBS which was proved as major risk factor for GBC in Jeju Island, Korea.
      Methods: Age and sex matchcase-control study was performed among 171 pairs of
      case and controls. The cases were patients who were diagnosedwith GBS, had
      definite clinical symptoms, and underwent a cholecystectomy in Cheju Halla
      General Hospital, Jeju,Korea during 2010-2014. The control group included 1:1 age
      and sex-matched participants without GBS at the HealthPromotion Center in the
      same institute during the same period. We compared the histories of previous
      chronic diseases(hypertension, diabetes, hyperlipidaemia, vascular occlusive
      diseases, or parity), alcohol consumption (standarddrinks/week [SDW]), smoking
      habits, body mass index (BMI), and presence of concomitant polypoid lesions of
      thegallbladder. Results: A dose-dependent positive relationship existed between
      BMI and the risk of GBS: BMI 23-27.4kg/m2, OR=2.5, , p=0.24; 27.5-29.9 kg/m2,
      OR=8.9, p=0.002; >=30 kg/m2, OR=7.2, p=0.004. A negative correlationexisted
      between alcohol consumption and the risk of GBS: Standard drinks per week (SDW),
      OR=0.24, p=0.002;15-29.9 SDW, OR=0.26, p=0.022; >=30 SDW, OR=0.2, 95% p=0.005.
      Conclusion: The present results suggest that ahigher BMI and less alcohol
      consumption are associated with a risk of symptomatic GBS.

PMID- 28441705
TI  - Oral Complications of The Oromaxillofacial Area Radiotherapy
AB  - Background: The incidence of malignancies is on the rise in different
      communities, making them the second mostimportant cause of mortality in developed
      countries. One of the treatment modalities for these malignancies, apartfrom
      surgery and chemotherapy, is radiotherapy which might in itself lead to some
      complications in the area receivingradiation. The present study was undertaken to
      evaluate the prevalence of oral complications in patients undergoingradiotherapy
      of the oromaxillofacial area in Shahid Ramazanzadeh Radiotherapy Center in Shahid
      Sadoughi Universityof Medical Sciences. Materials and Methods: The present
      descriptive/analytical study was carried out from 2014 to2015 on 144 patients
      with head and neck malignancies, referring to Shahid Ramazanzadeh Radiotherapy
      Center, Yazd,Iran. The patients underwent intraoral examinations before
      radiotherapy, during the second week after radiotherapy andat the end of
      radiotherapy. The patients' background data and the presence of oral
      complications were recorded in specialforms. Data were analyzed with SPSS 17,
      using chi-squared test. Results: Of 144 patients evaluated, 51 were maleand 93
      were female. During the final examination, all the subjects (100%) had mucositis,
      xerostomia and candidiasis,with 85.4% of the subjects (123 patients) suffering
      from gustatory disturbances. Although only 38.1% of the subjectshad oral ulcers
      at the end of the second week, all of them (100%) exhibited such lesions in the
      final examination.The prevalence rate of tooth hypersensitivity at this stage was
      22.9%. During the second examination, 117 subjects(83.3%) exhibited grade I
      trismus, 42 of which exhibited deterioration toward grade II during the final
      examination.Conclusion: The results of the present study showed a high rate of
      oral complications in patients undergoing head andneck radiotherapy. Mucositis,
      xerostomia and candidiasis were the most prevalent complications.

PMID- 28441707
TI  - Fentanyl Inhibits Tumorigenesis from Human Breast Stem Cells by Inducing
      Apoptosis
AB  - Fentanyl is an opioid analgesic that it is widely used in cancer patients. Since
      there have been reports of effectsof analgesic medications on the recurrence and
      development of resistance to treatment, influences of of fentanylon MCF-7 and
      HEK293 cells were evaluated. Cell viability and apoptosis were assessed by MTT
      assay and flowcytometry, respectively. Gene expression analysis was performed by
      quantitative real-time PCR assay for the Oct4,Sox2 and Nanog genes as stem cell
      markers and Bax, Bcl2, and p53 genes as apoptosis markers. MTT assay
      resultsshowed that fentanyl significantly inhibited the growth of MCF-7 cells in
      a dose-and time-dependent manner whilesignificantly increasing apoptosis. In
      contrast, decrease was noted in HEK-293 cells. In MCF-7 derived cancer stemcells,
      fentanyl treatment decreased the expression of Bax, Bcl2, Oct4, Sox2, Nanog genes
      when compared to untreatedcells. In HEK-293 stem cells, decrease was noted for
      Sox2, Nanog and Bax, but increase for Oct4. Our study supportsan antitumor role
      of fentanyl by inducing apoptosis and reducing numbers of cancer stem cells in
      the MCF-7 humanbreast adenocarcinoma line.

PMID- 28441706
TI  - A Comprehensive Model for Predicting Recurrence and Survival in Cases of Chinese
      Postoperative Invasive Breast Cancer
AB  - We investigated relationships between clinical pathologic data, molecular
      biomarkers and prognosis of invasive breastcancer based on a Chinese population.
      Immunohistochemistry (IHC) was used to assess the status of ER, PR, HER-2 andKi
      67, with fluorescence in situ hybridization (FISH) performed to further confirm
      HER-2 positivity with an equivocalresult (IHC 2+). Subsequently, Kaplan-Meier
      univariate and multivariate COX regression analyses of ER, PR, HER-2,Ki-67,
      clinical features, therapeutic status and follow-up data were performed according
      to the establishment principleof the Nottingham prognostic index (NPI). From this
      study, age, tumor size, lymph node status, ER, HER-2, Ki-67status were found to
      be associated with prognosis. Eventually, a prognostic model of (PI= (1.5*age) -
      size + (0.1*lymphnode status) - (0.5*ER) + (2*HER-2) - (0.2*Ki-67)) was
      established with 288 randomly selected patients and verifiedwith another 100
      cases with invasive breast cancer. Pearson correlation analysis demonstrated a
      significant positivecorrelation index of 0.376 (P=0.012<0.05) between the
      prognostic index (PI) and actual prognosis. Remarkably, theconsistency with the
      model predicted recurrence was 93% in the validation set. Therefore, it appears
      feasible to predictthe prognosis of individuals with invasive breast cancer and
      to determine optimal therapeutic strategy with this model.

PMID- 28441708
TI  - Dosimetric Comparison of Three Different Radiotherapy Techniques in Antrum
      Located Stomach Cancer
AB  - Background: The current optimal radiotherapy (RT) planning technique for stomach
      cancer is controversial. Thedesign of RT for stomach cancer is difficult and
      differs according to tumor localization. Dosimetric and clinical studieshave been
      performed in patients with different tumor localizations. This may be the main
      source of inconsistencies instudy results. For this reason, we attempted to find
      the optimal RT technique for patients with stomach cancer in similarlocations.
      Methods: This study was based on the computed tomography datasets of 20 patients
      with antrum-locatedstomach cancer. For each patient, treatments were designed
      using physical wedge-based conformal RT (WB-CRT),field-in-field intensity
      modulated RT (FIF-IMRT), and dynamic intensity-modulated RT (IMRT). The
      techniques werecompared in terms of expected target volume coverage and the dose
      to organs at risk (OAR) using a dose-volumehistogram analysis. Results: FIF-IMRT
      was the most homogenous technique, with a better homogeneity index thanWBCRT
      (p<0.001) or IMRT (p<0.001). However, IMRT had a better conformity index than
      WBCRT (p<0.001) orFIF-IMRT (p<0.001). Additionally, all OAR, including the
      kidneys, liver, and spinal cord, were better protected withIMRT than with WBCRT
      (p=0.023 to <0.001) or FIF-IMRT (p=0.028 to <0.001). Conclusions: In comparison
      toFIF-IMRT and WBCRT, IMRT appears to be the most appropriate technique for
      antrum-located stomach cancer. Toestablish whether IMRT is superior overall will
      require clinical studies, taking into account differences in both
      tumorlocalization (cardia, body, and antrum) and organ movement in patients with
      stomach cancer.

PMID- 28441709
TI  - Association of CYP3A5*3 and CYP1A1*2C Polymorphism with Development of Acute
      Myeloid Leukemia in Egyptian Patients
AB  - Aim: Cytochrome P450 (CYP) enzyme catalyzes the phase I metabolism reaction which
      metabolize endogenousand exogenous DNA-reactive chemical compounds and
      xenobiotics which could induce genotoxicity and increase therisk for leukemia. We
      aimed to detect frequency of CYP3A5*3 and CYP1A1*2C polymorphisms in Egyptian
      acutemyeloid leukemia (AML) patients and to determine role of allele's variants
      as a risk factor for developing leukemia.Patients and Methods: A case-control
      study was conducted on seventy acute myeloid leukemia patients and thirtycontrol
      subjects. Samples were analyzed for prevalence of CYP3A5*3 and CYP1A1*2C
      polymorphisms usingPCR - restriction fragment length polymorphism method.
      Results: CYP3A5*3 polymorphism (3/3) and (1/3) genotypewere significantly
      elevated in AML group compared to control group (p=0.002). However, no
      statistical significantdifferences were found between patients and control group
      as regard CYP1A1*2C polymorphism. Conclusion: Ourresults suggest that Egyptians
      carrying CYP3A5*3 polymorphism might have an increased risk of AML emphasizingthe
      significance of effective phase I detoxification in carcinogenesis.

PMID- 28441710
TI  - Analysis of Cisplatin-Induced Ototoxicity Risk Factors in Iranian Patients with
      Solid Tumors: a Cohort, Prospective and Single Institute Study
AB  - Background: Cisplatin has been associated with irreversible hearing damage. Up to
      now, there is no therapeuticintervention showing benefit in preventing Cisplatin
      induced ototoxicity. The aim of this study was to determinerisk factors
      contributing to hearing impairment after cisplatin administration in Iranian
      patients. Methods: Hearingthresholds of 124 patients before and after cisplatin
      administration were assessed with reference to pure-tone audiometryaverages at
      several frequencies from 2006 to 2010. Mean values were calculated at each tested
      frequency in each ear atbaseline and subsequent follow-up audiometry. Hearing
      impairment was assessed with the Munster score. Results: Themean age at diagnosis
      and the median cumulative Cisplatin dose were 47.3 years and 453.8 milligrams,
      respectively.Bilateral hearing loss, mostly of grade 1, and tinnitus were
      detected in 26% and 3.2% of patients. Logistic regressionanalysis showed that a
      high cumulative dose of cisplatin was the most important risk factor for
      developing hearingdamage (P=0.034). The most significant changes in the status of
      the auditory system and the most severe thresholdshift from base line (35 dB)
      were observed at a frequency of 8 kHz. Also, patients who received higher
      individualdoses of Cisplatin showed significantly more tinnitus (P=0.002).
      Conclusions: The results are testament to benefits ofroutine audiometric
      monitoring program during cisplatin-based chemotherapy. Further research should
      be performedto understand other risk factors, such as genetic predictors of
      Cisplatin-induced ototoxicity.

PMID- 28441712
TI  - Virus-Based Devices: Prospects for Allopoiesis.
AB  - The assembly line is a commonly invoked example of allopoiesis, the process
      whereby a system produces a different system than itself. In this sense, virus
      production in plants is an instance of bio-enabled bottom-up allopoiesis because
      the plant host can be regarded as a programmable assembly line for the virus.
      Reprogramming this assembly line and integrating it into a larger lineup of
      chemical manipulations has seen a flurry of activity recently, with more
      sophisticated systems emerging every year. The field of virus nanomaterials now
      has several subdisciplines that focus on virus shells as assemblers, scaffolds
      for molecular circuitry, chemical reactors, magnetic and photonic beacons, and
      therapeutic carriers. A case in point is the work reported by Brillault et al. in
      this issue of ACS Nano. They show how two types of animal virus coat proteins can
      be simultaneously expressed and efficiently assembled in plants into a complex
      virus-like particle of well-defined stoichiometry and composition. Such advances,
      combined with the promise of scalability and sustainability afforded by plants,
      paint a bright picture for the future of high-performance virus-based
      nanomaterials.

PMID- 28441713
TI  - Accelerating Advances in Science, Engineering, and Medicine through Nanoscience
      and Nanotechnology.

PMID- 28441714
TI  - Long non-coding RNA HOTAIR functions as miRNA sponge to promote the epithelial to
      mesenchymal transition in esophageal cancer.
AB  - BACKGROUND: Accumulating evidence indicates dysregulated expression of the long
      non-coding RNA HOTAIR (lncRNA-HOTAIR) may play a significant role in tumor
      progression. LncRNA-HOTAIR promotes several processes in esophageal cancer (EC),
      including cell growth, differentiation, invasion and migration. However, the
      mechanisms by which lncRNA-HOTAIR promotes invasion and migration EC remain
      unclear. METHODS: LncRNA-HOTAIR and miR-148a expression were quantified in 40
      paired human EC and tumor-adjacent tissues and EC cell lines by quantitative real
      time PCR (qRT-PCR). The CCK8 assay was used to quantify cell proliferation.
      Transwell invasion and migration assays were performed to assess cell invasion
      and migration. Western blot analysis was used to quantify E-cadherin, N-cadherin,
      Vimentin, and Snail2 expression. StarBase V2.0 was used to identify putative
      miRNA binding sites in lncRNA-HOTAIR; luciferase reporter assays were performed
      to validate the function of the predicted binding sites. RESULT: High lncRNA
      HOTAIR expression was associated with significantly poorer overall survival in
      EC. In vitro analysis showed lncRNA-HOTAIR enhanced EC cell proliferation,
      invasion and migration, and promoted the EMT. Mechanistic investigations revealed
      lncRNA-HOTAIR promotes the EMT by acting as a miR-148a sponge to positively
      regulate Snail2 expression. CONCLUSIONS: LncRNA-HOTAIR acts as a miR-148a sponge
      to positively regulate Snail2 expression, enhance cell invasion and metastasis,
      and promote the EMT in EC. LncRNA-HOTAIR may play an important role in tumor
      development and progression and represent a novel therapeutic target for EC.

PMID- 28441715
TI  - Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in
      human esophageal carcinoma cell line.
AB  - Paclitaxel (PTX) is one of the most effective drugs used in the treatment of
      esophageal cancer, however, paclitaxel resistance represents a key limitation
      during the treatment process. In this study, we investigated the changes of Bcl-2
      family members in the moderate paclitaxel-resistance of esophageal carcinoma
      EC109/PTX cells both in vitro and in vivo. Moreover, we evaluated the reversal
      effect using siRNAs and the recombinant inhibitor TW37 targeting Bcl-2, Bcl-XL
      and Mcl-1. Our findings show that downregulation of Bcl-2, Bcl-XL and Mcl-1 can
      significantly promote EC109/PTX cell apoptosis and reduce the EC109/PTX cell
      resistance index (RI). Furthermore, TW37 in combination with a P-gp inhibitor can
      synergistically reverse the paclitaxel resistance in EC109/PTX cells. These
      results suggest that targeting of the Bcl-2 family and P-gp is capable of
      reversing the resistance in EC109/PTX cells and the two-inhibitor combination may
      be a novel treatment strategy for resistant esophageal cancer.

PMID- 28441716
TI  - Noscapinoids bearing silver nanocrystals augmented drug delivery, cytotoxicity,
      apoptosis and cellular uptake in B16F1, mouse melanoma skin cancer cells.
AB  - PURPOSE: Noscapine (Nos) and reduced brominated analogue of noscapine (Red-Br
      Nos) prevent cellular proliferation and induce apoptosis in cancer cells either
      alone or in combination with other chemotherapeutic drugs. However, owing to poor
      physicochemical properties, Nos and Red-Br-Nos have demonstrated their anticancer
      activity at higher and multiple doses. Therefore, in present investigation,
      silver nanocrystals of noscapinoids (Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+
      nanocrystals) were customized to augment drug delivery, cytotoxicity, apoptosis
      and cellular uptake in B16F1 mouse melanoma cancer cells. METHODS AND RESULTS:
      Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals were prepared separately
      by precipitation method. The mean particle size of Nos-Ag2+ nanocrystals was
      measured to be 25.33+/-3.52nm, insignificantly (P>0.05) different from 27.43+/
      4.51nm of Red-Br-Nos-Ag2+ nanocrystals. Furthermore, zeta-potential of Nos-Ag2+
      nanocrystals was determined to be -25.3+/-3.11mV significantly (P<0.05) different
      from -15.2+/-3.33mV of Red-Br-Nos-Ag2+ nanocrystals. The shape of tailored
      nanocrystals was slightly spherical and or irregular in shape. The architecture
      of Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals was crystalline in
      nature. FT-IR spectroscopy evinced the successful interaction of Ag2+
      nanocrystals with Nos and Red-Br-Nos, respectively. The superior therapeutic
      efficacy of tailored nanocrystals was measured in terms of enhanced cytotoxicity,
      apoptosis and cellular uptake. The Nos-Ag2+ nanocrystals and Red-Br-Nos-Ag2+
      nanocrystals exhibited an IC50 of 16.6MUM and 6.5MUM, significantly (P<0.05)
      lower than 38.5MUM of Nos and 10.3MUM of Red-Br-Nos, respectively. Finally,
      cellular morphological alterations in B16F1 cells upon internalization of Nos
      Ag2+ nanocrystals and Red-Br-Nos-Ag2+ nanocrystals provided the evidences for
      accumulation within membrane-bound cytoplasmic vacuoles and in enlarged lysosomes
      and thus triggered mitochondria mediated apoptosis via caspase activation.
      CONCLUSION: Preliminary investigations substantiated that Nos-Ag2+ nanocrystals
      and Red-Br-Nos-Ag2+ nanocrystals must be further explored and utilized for the
      delivery of noscapinoids to melanoma cancer cells.

PMID- 28441717
TI  - Dexmedetomidine relieves formaldehyde-induced pain in rats through both alpha2
      adrenoceptor and imidazoline receptor.
AB  - Dexmedetomidine (DEX) is a highly selective alpha2 adrenergic receptor agonist.
      In this study, we investigated the analgesic effect and the underlying mechanisms
      of DEX on inflammatory visceral pain in rats. Twenty-five male Sprague Dawley
      (SD) rats were randomly divided into 5 groups, including control, sham, low dose
      DEX, medium dose DEX and high dose DEX group. Pain was induced with 10% formalin
      and scored every 15min till 2 h-post the induction. Hematoxylin-eosin (HE)
      staining was used to evaluate the toxicity of DEX on spinal cord neurons.
      Acetycholine (Ach) and noradrenaline (NA) levels were determined by using ELISA
      method. The expressions of natural nitric oxide synthase (nNOS), protein kinase
      gamma (PKCgamma) and protease-activated receptor 2 (PAR2) were determined by
      using western blot. DEX treatment relieved formaldehyde-induced pain in rats in a
      dose-dependent manner. Furthermore, DEX showed little neuro-toxicity on the
      spinal cord neurons, even at the highest dosage used in our study. Ach level was
      significantly increased in Sham group compared with control group. DEX treatment
      decreased NA levels and increased Ach levels in the incubation medium of spinal
      cord sections. Western blot analysis showed that the expression of nNOS, PKCgamma
      and PAR2 was significantly decreased in DEX group compared with Sham group,
      whereas these effects of DEX on nNOS, PKCgamma and PAR2 were blocked by both
      yohimbine and idazoxan, indicating that the analgesic effect of DEX is mediated
      by both alpha2 adrenergic receptor and imidazoline receptor. Yohimbine and
      idazoxan treatment significantly enhanced pain scores compared to DEX group, and
      which antagonizes the effects DEX. In conclusion, our study demonstrated that DEX
      could inhibit formaldehyde-induced pain by inhibiting nNOS, PKCgamma and PAR2
      expression through alpha2 adrenergic receptor and imidazoline receptor.

PMID- 28441718
TI  - Therapeutic effect of melittin on a rat model of chronic prostatitis induced by
      Complete Freund's Adjuvant.
AB  - OBJECTIVES: The present study was aimed to establish a model of chronic
      prostatitis in rat with the use of intraprostatic injection of Complete Freund's
      Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin
      on the newly-developed chronic prostatic pain model. METHODS: Adult male Sprague
      Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the
      prostate. Twelve days after model rats of the treatment group were injected
      melittin into the prostate, while those of the control group received sterile
      saline injection. The nociceptive effects of CFA were evaluated by using a
      behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA
      injection and 6, 12, and 18days after CFA injection. After the in-live study was
      done, the prostate was collected for histological examination of inflammatory
      cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial
      fibrillary acidic protein (GFAP) in spinal cord were determined using
      immunohistochemistry. Rats of the sham control group received intraprostatic
      injection of sterile saline and were studied using the same methods RESULTS:
      Intraprostatic CFA injection induced local allodynia that lasted over at least 2
      weeks. The pain behavior of rat was associated with increases in inflammatory
      cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in
      spinal cord were also elevated. Treatment with melittin significantly raised pain
      threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP
      expression. CONCLUSION: Intraprostatic injection of CFA induced neurogenic
      prostatitis and prostatic pain. The established model will be useful to the study
      of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and
      analgesic effects on the chronic prostatic pain model, suggesting melittin may
      hold promise as a novel therapeutic for treatment of CP/CPPS.

PMID- 28441719
TI  - Suppression of Oxidative Stress and NFkappaB/MAPK Signaling by Lyophilized Black
      Raspberries for Esophageal Cancer Prevention in Rats.
AB  - Research in the laboratory has shown that lyophilized black raspberries (BRB)
      significantly inhibit N-nitrosomethylbenzylamine (NMBA)-induced esophageal
      squamous cell carcinogenesis in rats. The objective of the present study is to
      characterize the underlying mechanism(s) of anti-cancer action of BRB in this
      preclinical animal model focusing on oxidative stress and its related oncogenic
      signaling pathways. Esophageal epithelial tissues were collected and assessed for
      markers of oxidative stress and nuclear factor kappaB (NFkappaB) and mitogen
      activated protein kinase (MAPK). BRB reduced the incidence of esophageal cancer
      from 100% in NMBA-treated rats to 81.5% in rats treated with NMBA plus BRB (p <
      0.05). Tumor multiplicity was reduced from 4.73 +/- 0.45 tumors per esophagus in
      NMBA-treated rats to 1.44 +/- 0.26 in rats treated with NMBA plus BRB (p <
      0.001). The data indicated that NMBA treatment increased production of hydrogen
      peroxide and lipid hydroperoxide, reduced expression and activity of glutathione
      peroxidase and superoxide dismutase 2, and activated NFkappaB/MAPK signaling in
      rat esophagus. The study's results show that BRB reverses oxidative stress and
      suppresses NFkappaB/MAPK pathways, which could be the mechanisms for esophageal
      cancer chemopreventive action of BRB in rats.

PMID- 28441720
TI  - Association of Polyphenol Biomarkers with Cardiovascular Disease and Mortality
      Risk: A Systematic Review and Meta-Analysis of Observational Studies.
AB  - Epidemiologic studies have suggested an inverse association between flavonoids
      and cardiovascular disease (CVD). However, the results might have been influenced
      by the use of dietary assessment methods, which are error prone. The aim of this
      paper was to systematically review and analyse the literature for evidence of
      associations between polyphenol biomarkers and CVD and mortality risk in
      observational studies. Eligible studies were identified through PubMed, Web of
      Science, and reference lists. Multivariable adjusted associations were extracted.
      Data were log-transformed and pooled using the random effects model. In total,
      eight studies were included, investigating 16 different polyphenol biomarkers in
      association with CVD and mortality. Blood and urine were used as biospecimens,
      and enterolactone, a lignan metabolite, was most often investigated. Three meta
      analyses were conducted investigating the association between enterolactone, and
      all-cause and CVD mortality, and non-fatal myocardial infarction. A 30% and 45%
      reduced all-cause and CVD mortality risk were revealed at higher enterolactone
      concentrations. Furthermore, inverse associations were observed between
      polyphenol biomarkers and all-cause mortality, kaempferol, and acute coronary
      syndrome. There is evidence to suggest that enterolactone is associated with a
      lower CVD mortality risk. This emphasises the importance of the role of the
      microbiota in disease prevention. To strengthen the evidence, more studies are
      warranted.

PMID- 28441722
TI  - Experimental Demonstration and Circuitry for a Very Compact Coil-Only Pulse Echo
      EMAT.
AB  - This experimental study demonstrates for the first time a solid-state circuitry
      and design for a simple compact copper coil (without an additional bulky
      permanent magnet or bulky electromagnet) as a contactless electromagnetic
      acoustic transducer (EMAT) for pulse echo operation at MHz frequencies. A pulsed
      ultrasound emission into a metallic test object is electromagnetically excited by
      an intense MHz burst at up to 500 A through the 0.15 mm filaments of the
      transducer. Immediately thereafter, a smoother and quasi "DC-like" current of 100
      A is applied for about 1 ms and allows an echo detection. The ultrasonic pulse
      echo operation for a simple, compact, non-contacting copper coil is new.
      Application scenarios for compact transducer techniques include very narrow and
      hostile environments, in which, e.g., quickly moving metal parts must be tested
      with only one, non-contacting ultrasound shot. The small transducer coil can be
      operated remotely with a cable connection, separate from the much bulkier supply
      circuitry. Several options for more technical and fundamental progress are
      discussed.

PMID- 28441721
TI  - Pathogenic or Therapeutic Extracellular Vesicles in Rheumatic Diseases: Role of
      Mesenchymal Stem Cell-Derived Vesicles.
AB  - Extracellular vesicles (EVs) are important mediators of cell-to-cell
      communication pathways via the transport of proteins, mRNA, miRNA and lipids.
      There are three main types of EVs, exosomes, microparticles and apoptotic bodies,
      which are classified according to their size and biogenesis. EVs are secreted by
      all cell types and their function reproduces that of the parental cell. They are
      involved in many biological processes that regulate tissue homeostasis and
      physiopathology of diseases. In rheumatic diseases, namely osteoarthritis (OA)
      and rheumatoid arthritis (RA), EVs have been isolated from synovial fluid and
      shown to play pathogenic roles contributing to progression of both diseases. By
      contrast, EVs may have therapeutic effect via the delivery of molecules that may
      stop disease evolution. In particular, EVs derived from mesenchymal stem cells
      (MSCs) reproduce the main functions of the parental cells and therefore represent
      the ideal type of EVs for modulating the course of either disease. The aim of
      this review is to discuss the role of EVs in OA and RA focusing on their
      potential pathogenic effect and possible therapeutic options. Special attention
      is given to MSCs and MSC-derived EVs for modulating OA and RA progression with
      the perspective of developing innovative therapeutic strategies.

PMID- 28441723
TI  - Phenolic Compounds Isolated from Caesalpinia coriaria Induce S and G2/M Phase
      Cell Cycle Arrest Differentially and Trigger Cell Death by Interfering with
      Microtubule Dynamics in Cancer Cell Lines.
AB  - Caesalpinia coriaria (C. coriaria), also named cascalote, has been known
      traditionally in Mexico for having cicatrizing and inflammatory properties.
      Phytochemical reports on Caesalpinia species have identified a high content of
      phenolic compounds and shown antineoplastic effects against cancer cells. The aim
      of this study was to isolate and identify the active compounds of a
      water:acetone:ethanol (WAE) extract of C. coriaria pods and characterize their
      cytotoxic effect and cell death induction in different cancer cell lines. The
      compounds isolated and identified by chromatography and spectroscopic analysis
      were stigmasterol, ethyl gallate and gallic acid. Cytotoxic assays on cancer
      cells showed different ranges of activities. A differential effect on cell cycle
      progression was observed by flow cytometry. In particular, ethyl gallate and
      tannic acid induced G2/M phase cell cycle arrest and showed interesting effect on
      microtubule stabilization in Hep3B cells observed by immunofluorescence. The
      induction of apoptosis was characterized by morphological characteristic changes,
      and was supported by increases in the ratio of Bax/Bcl-2 expression and
      activation of caspase 3/7. This work constitutes the first phytochemical and
      cytotoxic study of C. coriaria and showed the action of its phenolic constituents
      on cell cycle, cell death and microtubules organization.

PMID- 28441724
TI  - Multiple UDP-Glucuronosyltransferase and Sulfotransferase Enzymes are Responsible
      for the Metabolism of Verproside in Human Liver Preparations.
AB  - Verproside, an active iridoid glycoside component of Veronica species, such as
      Pseudolysimachion rotundum var. subintegrum and Veronica anagallis-aquatica,
      possesses anti-asthma, anti-inflammatory, anti-nociceptive, antioxidant, and
      cytostatic activities. Verproside is metabolized into nine metabolites in human
      hepatocytes: verproside glucuronides (M1, M2) via glucuronidation, verproside
      sulfate (M3) via sulfation, picroside II (M4) and isovanilloylcatalpol (M5) via O
      methylation, M4 glucuronide (M6) and M4 sulfate (M8) via further glucuronidation
      and sulfation of M4, and M5 glucuronide (M7) and M5 sulfate (M9) via further
      glucuronidation and sulfation of M5. Drug-metabolizing enzymes responsible for
      verproside metabolism, including sulfotransferase (SULT) and UDP
      glucuronosyltransferase (UGT), were characterized. The formation of verproside
      glucuronides (M1, M2), isovanilloylcatalpol glucuronide (M7), and picroside II
      glucuronide (M6) was catalyzed by commonly expressed UGT1A1 and UGT1A9 and
      gastrointestinal-specific UGT1A7, UGT1A8, and UGT1A10, consistent with the higher
      intrinsic clearance values for the formation of M1, M2, M6, and M7 in human
      intestinal microsomes compared with those in liver microsomes. The formation of
      verproside sulfate (M3) and M5 sulfate (M9) from verproside and
      isovanilloylcatalpol (M5), respectively, was catalyzed by SULT1A1. Metabolism of
      picroside II (M4) into M4 sulfate (M8) was catalyzed by SULT1A1, SULT1E1,
      SULT1A2, SULT1A3, and SULT1C4. Based on these results, the pharmacokinetics of
      verproside may be affected by the co-administration of relevant UGT and SULT
      inhibitors or inducers.

PMID- 28441725
TI  - Sweet Taste Receptor Activation in the Gut Is of Limited Importance for Glucose
      Stimulated GLP-1 and GIP Secretion.
AB  - Glucose stimulates the secretion of the incretin hormones: glucagon-like peptide
      1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). It is debated
      whether the sweet taste receptor (STR) triggers this secretion. We investigated
      the role of STR activation for glucose-stimulated incretin secretion from an
      isolated perfused rat small intestine and whether selective STR activation by
      artificial sweeteners stimulates secretion. Intra-luminal administration of the
      STR agonists, acesulfame K (3.85% w/v), but not sucralose (1.25% w/v) and
      stevioside (2.5% w/v), stimulated GLP-1 secretion (acesulfame K: 31 +/- 3 pmol/L
      vs. 21 +/- 2 pmol/L, p < 0.05, n = 6). In contrast, intra-arterial administration
      of sucralose (10 mM) and stevioside (10 mM), but not acesulfame K, stimulated GLP
      1 secretion (sucralose: 51 +/- 6 pmol/L vs. 34 +/- 4 pmol/L, p < 0.05;
      stevioside: 54 +/- 6 pmol/L vs. 32 +/- 2 pmol/L, p < 0.05, n = 6), while 0.1 mM
      and 1 mM sucralose did not affect the secretion. Luminal glucose (20% w/v)
      doubled GLP-1 and GIP secretion, but basolateral STR inhibition by gurmarin (2.5
      ug/mL) or the inhibition of the transient receptor potential cation channel 5
      (TRPM5) by triphenylphosphine oxide (TPPO) (100 uM) did not attenuate the
      responses. In conclusion, STR activation does not drive GIP/GLP-1 secretion
      itself, nor does it have a role for glucose-stimulated GLP-1 or GIP secretion.

PMID- 28441726
TI  - Sodium and Potassium Intake in Healthy Adults in Thessaloniki Greater
      Metropolitan Area-The Salt Intake in Northern Greece (SING) Study.
AB  - A reduction in population sodium (as salt) consumption is a global health
      priority, as well as one of the most cost-effective strategies to reduce the
      burden of cardiovascular disease. High potassium intake is also recommended to
      reduce cardiovascular disease. To establish effective policies for setting
      targets and monitoring effectiveness within each country, the current level of
      consumption should be known. Greece lacks data on actual sodium and potassium
      intake. The aim of the present study was therefore to assess dietary salt (using
      sodium as biomarker) and potassium intakes in a sample of healthy adults in
      northern Greece, and to determine whether adherence to a Mediterranean diet is
      related to different sodium intakes or sodium-to-potassium ratio. A cross
      sectional survey was carried out in the Thessaloniki greater metropolitan area
      (northern Greece) (n = 252, aged 18-75 years, 45.2% males). Participants' dietary
      sodium and potassium intakes were determined by 24-hour urinary sodium and
      potassium excretions. In addition, we estimated their adherence to Mediterranean
      diet by the use of an 11-item MedDietScore (range 0-55). The mean sodium
      excretion was 175 (SD 72) mmol/day, equivalent to 4220 (1745) mg of sodium or
      10.7 (4.4) g of salt per day, and the potassium excretion was 65 (25) mmol/day,
      equivalent to 3303 (1247) mg per day. Men had higher sodium and potassium
      excretions compared to women. Only 5.6% of the sample had salt intake <5 g/day,
      which is the target intake recommended by the World Health Organization. Mean
      sodium-to-potassium excretion ratio was 2.82 (1.07). There was no significant
      difference in salt or potassium intake or their ratio across MedDietScore
      quartiles. No significant relationships were found between salt intake and
      adherence to a Mediterranean diet, suggesting that the perception of the health
      benefits of the Mediterranean diet does not hold when referring to salt
      consumption. These results suggest the need for a larger, nation-wide survey on
      salt intake in Greece and underline the importance of continuation of salt
      reduction initiatives in Greece.

PMID- 28441728
TI  - Imaging of the Finger Vein and Blood Flow for Anti-Spoofing Authentication Using
      a Laser and a MEMS Scanner.
AB  - A new authentication method employing a laser and a scanner is proposed to
      improve image contrast of the finger vein and to extract blood flow pattern for
      liveness detection. A micromirror reflects a laser beam and performs a uniform
      raster scan. Transmissive vein images were obtained, and compared with those of
      an LED. Blood flow patterns were also obtained based on speckle images in
      perfusion and occlusion. Curvature ratios of the finger vein and blood flow
      intensities were found to be nearly constant, regardless of the vein size, which
      validated the high repeatability of this scheme for identity authentication with
      anti-spoofing.

PMID- 28441727
TI  - Job Strain and Casual Blood Pressure Distribution: Looking beyond the Adjusted
      Mean and Taking Gender, Age, and Use of Antihypertensives into Account. Results
      from ELSA-Brasil.
AB  - Methodological issues are pointed to as the main sources of inconsistencies in
      studies about the association between job strain and blood pressure
      (BP)/hypertension. Our aim was to analyze the relationship between job strain and
      the whole BP distribution, as well as potential differences by gender, age, and
      use of antihypertensives. Additionally, we addressed issues relating to the
      operationalization of the exposure and outcome variables that influence the study
      of their inter-relations. We evaluated the baseline date of 12,038 participants
      enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) (2008
      2010), a multicenter cohort study of 35-74-year-old civil servants. Job strain
      was assessed by the Demand-Control-Support Questionnaire. The distribution of
      casual BP by categories of job strain was compared by a combination of
      exploratory techniques. Participants were classified into three subgroups
      (normotensives, medicated hypertensives, and unmedicated hypertensives), and
      analyses were stratified by gender and age. The relationship between job strain
      and casual BP varied along the whole outcome distribution. Hypertensive
      participants had greater differences in casual BP by job strain category,
      especially medicated hypertensives. Differences in casual BP were also greater
      for systolic than for diastolic BP and for older participants. No differences
      were encountered by gender. The exclusion of participants susceptible to
      misclassification for the exposure and outcome variables increased the
      differences observed between the categories of low and high job strain. In
      conclusion, the relationship between job strain and casual BP varied along the
      whole outcome distribution and by use of antihypertensive drugs, age, and BP
      parameter evaluated. Misclassification for exposure and outcome variables should
      be considered in analyses of this topic.

PMID- 28441729
TI  - The Influence of Hydroxyapatite Nanoparticle Morphology on Embryonic Development
      in a Zebrafish Exposure Model.
AB  - Nanomaterials are used in many different industries such as cosmetics, food,
      clothing, and electronics. There is increasing concern that exposure to
      nanoparticles (NPs) during pregnancy can adversely affect fetal development. It
      is well known that the size, charge, and chemistry of a nanoparticle can modulate
      embryological development. The role that particle morphology plays on early
      development, however, is still widely unknown. The present study aims to
      investigate the effect of hydroxyapatite nanoparticle (HANP) morphology on
      embryological development in a zebrafish exposure model. Four distinct HANP
      morphologies (dots, long rods, sheets, and fibers) were fabricated and
      characterized. Zebrafish embryos were exposed to HANPs (0-100 mg/L), and
      viability and developmental deformities were evaluated for up to 5 days post
      fertilization (dpf). Malformations such as pericardial edema and axial curvature
      were apparent in embryos as early as 1 dpf, following exposure to the dot and
      fiber particles, and developed in embryos by 3 dpf in the sheet and long rod
      particle groups. Minimal death was observed in response to dot, long rod, and
      sheet particles (<=25%), while fiber particles induced overwhelming toxicity
      (<=60%) after 1 dpf, and complete toxicity during all subsequent time points.
      Collectively, these results suggest that nanoparticle morphology can
      significantly impact embryological development and should be a required
      consideration when designing nanomaterials for commercial use.

PMID- 28441730
TI  - Regulatory miRNAs in Colorectal Carcinogenesis and Metastasis.
AB  - Colorectal cancer is one of the most common malignancies and is the second
      leading cause of cancer-related death world-wide, which is linked to genetic
      mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs,
      one of the categories of epigenetics, have been demonstrated significant roles in
      carcinogenesis and progression through regulating of oncogenic signaling
      pathways, stem cells, epithelial-mesenchymal transition, and metastasis. This
      review summarizes the roles of microRNAs in the regulating of Wnt, Ras, TGF-beta,
      and inflammatory signaling pathways, stemness, and epithelial-mesenchymal
      transition, for carcinogenesis and metastasis in colorectal cancer. Improving our
      understanding of the mechanisms of regulatory interactions of microRNAs with
      signaling pathways in colorectal cancer formation and progression will aid in
      determining the genes responsible for colorectal cancer initiation, progression,
      metastasis, and recurrence and, finally, in developing personalized approaches
      for cancer prevention and therapy.

PMID- 28441731
TI  - Polyphenolic Compounds and Digestive Enzymes: In Vitro Non-Covalent Interactions.
AB  - The digestive enzymes-polyphenolic compounds (PCs) interactions behind the
      inhibition of these enzymes have not been completely studied. The existing
      studies have mainly analyzed polyphenolic extracts and reported inhibition
      percentages of catalytic activities determined by UV-Vis spectroscopy techniques.
      Recently, pure PCs and new methods such as isothermal titration calorimetry and
      circular dichroism have been applied to describe these interactions. The present
      review focuses on PCs structural characteristics behind the inhibition of
      digestive enzymes, and progress of the used methods. Some characteristics such as
      molecular weight, number and position of substitution, and glycosylation of
      flavonoids seem to be related to the inhibitory effect of PCs; also, this effect
      seems to be different for carbohydrate-hydrolyzing enzymes and proteases. The
      digestive enzyme-PCs molecular interactions have shown that non-covalent binding,
      mostly by van der Waals forces, hydrogen binding, hydrophobic binding, and other
      electrostatic forces regulate them. These interactions were mainly associated to
      non-competitive type inhibitions of the enzymatic activities. The present review
      emphasizes on the digestive enzymes such as alpha-glycosidase (AG), alpha-amylase
      (PA), lipase (PL), pepsin (PE), trypsin (TP), and chymotrypsin (CT). Existing
      studies conducted in vitro allow one to elucidate the characteristics of the
      structure-function relationships, where differences between the structures of PCs
      might be the reason for different in vivo effects.

PMID- 28441732
TI  - Modified Nucleotides as Substrates of Terminal Deoxynucleotidyl Transferase.
AB  - The synthesis of novel modified nucleotides and their incorporation into DNA
      sequences opens many possibilities to change the chemical properties of
      oligonucleotides (ONs), and, therefore, broaden the field of practical
      applications of modified DNA. The chemical synthesis of nucleotide derivatives,
      including ones bearing thio-, hydrazino-, cyano- and carboxy groups as well as 2
      pyridone nucleobase-containing nucleotides was carried out. The prepared
      compounds were tested as substrates of terminal deoxynucleotidyl transferase
      (TdT). The nucleotides containing N4-aminocytosine, 4-thiouracil as well as 2
      pyridone, 4-chloro- and 4-bromo-2-pyridone as a nucleobase were accepted by TdT,
      thus allowing enzymatic synthesis of 3'-terminally modified ONs. The successful
      UV-induced cross-linking of 4-thiouracil-containing ONs to TdT was carried out.
      Enzymatic post-synthetic 3'-modification of ONs with various photo- and
      chemically-reactive groups opens novel possibilities for future applications,
      especially in analysis of the mechanisms of polymerases and the development of
      photo-labels, sensors, and self-assembling structures.

PMID- 28441733
TI  - Bioactivity Studies on Titania Coatings and the Estimation of Their Usefulness in
      the Modification of Implant Surfaces.
AB  - Morphologically different titania coatings (nanofibers (TNFs), nanoneedles
      (TNNs), and nanowires (TNWs)) were studied as potential biomedical materials. The
      abovementioned systems were produced in situ on Ti6Al4V substrates via direct
      oxidation processes using H2O2 and H2O2/CaCl2 agents, and via thermal oxidation
      in the presence of Ar and Ar/H2O2. X-ray diffraction and Raman spectroscopy have
      been used to structurally characterize the produced materials. The morphology
      changes on the titanium alloy surface were investigated using scanning electron
      microscopy. The bioactivity of the samples has been estimated by the analysis of
      the produced titania coatings' biocompatibility, and by the determination of
      their ability to reduce bacterial biofilm formation. The photoactivity of the
      produced nanocoatings was also analyzed, in order to determine the possibility of
      using titania coated implant surfaces in the sterilization process of implants.
      Photocatalytic activity was estimated using the methylene blue photodegradation
      kinetics, in the presence of UV light.

PMID- 28441734
TI  - Chloroviruses Have a Sweet Tooth.
AB  - Chloroviruses are large double-stranded DNA (dsDNA) viruses that infect certain
      isolates of chlorella-like green algae. They contain up to approximately 400
      protein-encoding genes and 16 transfer RNA (tRNA) genes. This review summarizes
      the unexpected finding that many of the chlorovirus genes encode proteins
      involved in manipulating carbohydrates. These include enzymes involved in making
      extracellular polysaccharides, such as hyaluronan and chitin, enzymes that make
      nucleotide sugars, such as GDP-L-fucose and GDP-D-rhamnose and enzymes involved
      in the synthesis of glycans attached to the virus major capsid proteins. This
      latter process differs from that of all other glycoprotein containing viruses
      that traditionally use the host endoplasmic reticulum and Golgi machinery to
      synthesize and transfer the glycans.

PMID- 28441736
TI  - A Weighted Belief Entropy-Based Uncertainty Measure for Multi-Sensor Data Fusion.
AB  - In real applications, how to measure the uncertain degree of sensor reports
      before applying sensor data fusion is a big challenge. In this paper, in the
      frame of Dempster-Shafer evidence theory, a weighted belief entropy based on Deng
      entropy is proposed to quantify the uncertainty of uncertain information. The
      weight of the proposed belief entropy is based on the relative scale of a
      proposition with regard to the frame of discernment (FOD). Compared with some
      other uncertainty measures in Dempster-Shafer framework, the new measure focuses
      on the uncertain information represented by not only the mass function, but also
      the scale of the FOD, which means less information loss in information
      processing. After that, a new multi-sensor data fusion approach based on the
      weighted belief entropy is proposed. The rationality and superiority of the new
      multi-sensor data fusion method is verified according to an experiment on
      artificial data and an application on fault diagnosis of a motor rotor.

PMID- 28441735
TI  - Effects of Flavonoids and Triterpene Analogues from Leaves of Eleutherococcus
      sieboldianus (Makino) Koidz. 'Himeukogi' in 3T3-L1 Preadipocytes.
AB  - Eleutherococcus sieboldianus (Makino) Koidz. is a local product from the area in
      and around Yonezawa City in Yamagata Prefecture, Japan. It has been used as a
      medicinal plant for a long time. We isolated and identified four types of
      flavonoid glycosides [astragalin (1), isoquercetin (2), rhamnocitrin 3-O
      glucoside (3), and nicotiflorin (4)], a triterpene [methyl hederagenin (5)], and
      three types of triterpene glycosides [delta-hederin (6), echinocystic acid 3-O
      arabinoside (7), and cauloside B (8)] from the methanol extract of E.
      sieboldianus, which regulates lipid accumulation in 3T3-L1 preadipocytes. Among
      the compounds isolated, 2 and 8 up- and down-regulated lipid accumulation and
      insulin induced adipocyte differentiation in 3T3-L1 preadipocytes. Compound 2
      induced up-regulation of lipid accumulation and decreased adipocyte size, while 8
      down-regulated lipid accumulations without decreasing cell size. Additionally, 2
      increased adipogenic proteins [peroxisome proliferator-activated receptor gamma
      (PPARgamma), CCAAT/enhancer-binding protein alpha (C/EBPalpha), and fatty-acid
      binding protein 4 (FABP4)]. In contrast, 8 decreased the levels of all adipogenic
      proteins and glucose transporter type 4 (GLUT4), but increased adiponectin.

PMID- 28441738
TI  - Simulation Study of the Localization of a Near-Surface Crack Using an Air-Coupled
      Ultrasonic Sensor Array.
AB  - The importance of Non-Destructive Testing (NDT) to check the integrity of
      materials in different fields of industry has increased significantly in recent
      years. Actually, industry demands NDT methods that allow fast (preferably non
      contact) detection and localization of early-stage defects with easy-to-interpret
      results, so that even a non-expert field worker can carry out the testing. The
      main challenge is to combine as many of these requirements into one single
      technique. The concept of acoustic cameras, developed for low frequency NDT,
      meets most of the above-mentioned requirements. These cameras make use of an
      array of microphones to visualize noise sources by estimating the Direction Of
      Arrival (DOA) of the impinging sound waves. Until now, however, because of
      limitations in the frequency range and the lack of integrated nonlinear post
      processing, acoustic camera systems have never been used for the localization of
      incipient damage. The goal of the current paper is to numerically investigate the
      capabilities of locating incipient damage by measuring the nonlinear airborne
      emission of the defect using a non-contact ultrasonic sensor array. We will
      consider a simple case of a sample with a single near-surface crack and prove
      that after efficient excitation of the defect sample, the nonlinear defect
      responses can be detected by a uniform linear sensor array. These responses are
      then used to determine the location of the defect by means of three different DOA
      algorithms. The results obtained in this study can be considered as a first step
      towards the development of a nonlinear ultrasonic camera system, comprising the
      ultrasonic sensor array as the hardware and nonlinear post-processing and source
      localization software.

PMID- 28441737
TI  - Commitment of Scaffold Proteins in the Onco-Biology of Human Colorectal Cancer
      and Liver Metastases after Oxaliplatin-Based Chemotherapy.
AB  - Scaffold proteins play pivotal roles in the regulation of signaling pathways,
      integrating external and internal stimuli to various cellular outputs. We report
      the pattern of cellular and subcellular expression of scaffoldins angiomotin-like
      2 (AmotL2), FK506 binding protein 5 (FKBP51) and IQ motif containing GTPase
      activating protein 1 (IQGAP1) in colorectal cancer (CRC) and metastases in liver
      resected after oxaliplatin-based chemotherapy (CT). Positive immunostaining for
      the three scaffoldins was found in most cells in healthy colon, tumor, healthy
      liver and metastasized liver. The patterns of expression of AmotL2, FKBP51 and
      IQGAP1 show the greatest variability in immune system cells and neurons and glia
      cells and the least in blood vessel cells. The simultaneous subcellular
      localization in tumor cells and other cell types within the tumor suggest an
      involvement of these three scaffoldins in cancer biology, including a role in
      Epithelial Mesenchymal Transition. The display in differential localization and
      quantitative expression of AmotL2, FKBP51, and IQGAP1 could be used as biomarkers
      for more accurate tumor staging and as potential targets for anti-cancer
      therapeutics by blocking or slowing down their interconnecting functions. Tough
      further research needs to be done in order to improve these assessments.

PMID- 28441739
TI  - The Use of IMMUs in a Water Environment: Instrument Validation and Application of
      3D Multi-Body Kinematic Analysis in Medicine and Sport.
AB  - The aims of the present study were the instrumental validation of inertial
      magnetic measurements units (IMMUs) in water, and the description of their use in
      clinical and sports aquatic applications applying customized 3D multi-body
      models. Firstly, several tests were performed to map the magnetic field in the
      swimming pool and to identify the best volume for experimental test acquisition
      with a mean dynamic orientation error lower than 5 degrees . Successively, the
      gait and the swimming analyses were explored in terms of spatiotemporal and joint
      kinematics variables. The extraction of only spatiotemporal parameters
      highlighted several critical issues and the joint kinematic information has shown
      to be an added value for both rehabilitative and sport training purposes.
      Furthermore, 3D joint kinematics applied using the IMMUs provided similar
      quantitative information than that of more expensive and bulky systems but with a
      simpler and faster setup preparation, a lower time consuming processing phase, as
      well as the possibility to record and analyze a higher number of strides/strokes
      without limitations imposed by the cameras.

PMID- 28441740
TI  - A Miniature Aerosol Sensor for Detecting Polydisperse Airborne Ultrafine
      Particles.
AB  - Counting and sizing of polydisperse airborne nanoparticles have attracted most
      attentions owing to increasing widespread presence of airborne engineered
      nanoparticles or ultrafine particles. Here we report a miniature aerosol sensor
      to detect particle size distribution of polydisperse ultrafine particles based on
      ion diffusion charging and electrical detection. The aerosol sensor comprises a
      couple of planar electrodes printed on two circuit boards assembled in parallel,
      where charging, precipitation and measurement sections are integrated into one
      chip, which can detect aerosol particle size in of 30-500 nm, number
      concentration in range of 5 * 102-107 /cm3. The average relative errors of the
      measured aerosol number concentration and the particle size are estimated to be
      12.2% and 13.5% respectively. A novel measurement scheme is proposed to actualize
      a real-time detection of polydisperse particles by successively modulating the
      measurement voltage and deducing the particle size distribution through a smart
      data fusion algorithm. The effectiveness of the aerosol sensor is experimentally
      demonstrated via measurements of polystyrene latex (PSL) aerosol and nucleic acid
      aerosol, as well as sodium chloride aerosol particles.

PMID- 28441742
TI  - The Reliability of the Mediterranean Diet Quality Index (KIDMED) Questionnaire.
AB  - The purpose of the present study was to determine the test-retest reliability of
      the Mediterranean Diet Quality Index (KIDMED) questionnaire in college students.
      Two hundred and seventy-six college students (127 men, 46%; 149 women, 54%; mean
      age 19.70 +/- 1.32 years; mean height 1.75 +/- 0.09 m; mean weight 69.28 +/-
      13.84 kg; mean body-mas index 22.41 +/- 3.19 kg/m2) participated in the study. To
      investigate the reliability of the KIDMED questionnaire, the participants were
      asked to complete the questionnaire on two occasions two weeks apart, stratified
      by gender. Kappa statistics showed moderate to excellent agreement (ranging from
      0.504 to 0.849) in the total sample and moderate to excellent agreement in both
      men (ranging from 0.467 to 0.803) and women (ranging from 0.435 to 0.927).
      Results in the total KIDMED score showed a moderate correlation between two
      occasions inthe total sample (kappa = 0.597, p < 0.001) and in women (kappa =
      0.586, p < 0.001) and a good correlation in men (kappa = 0.611, p < 0.001). Our
      study shows that the KIDMED questionnaire is a reliable instrument for assessing
      adherence to the Mediterranean diet in college students. Future studies should
      focus on investigating the reliability of the questionnaire in other countries
      and in different age groups for generating comparable data.

PMID- 28441743
TI  - Smartphone Location-Independent Physical Activity Recognition Based on
      Transportation Natural Vibration Analysis.
AB  - Activity recognition through smartphones has been proposed for a variety of
      applications. The orientation of the smartphone has a significant effect on the
      recognition accuracy; thus, researchers generally propose using features
      invariant to orientation or displacement to achieve this goal. However, those
      features reduce the capability of the recognition system to differentiate among
      some specific commuting activities (e.g., bus and subway) that normally involve
      similar postures. In this work, we recognize those activities by analyzing the
      vibrations of the vehicle in which the user is traveling. We extract natural
      vibration features of buses and subways to distinguish between them and address
      the confusion that can arise because the activities are both static in terms of
      user movement. We use the gyroscope to fix the accelerometer to the direction of
      gravity to achieve an orientation-free use of the sensor. We also propose a
      correction algorithm to increase the accuracy when used in free living conditions
      and a battery saving algorithm to consume less power without reducing
      performance. Our experimental results show that the proposed system can
      adequately recognize each activity, yielding better accuracy in the detection of
      bus and subway activities than existing methods.

PMID- 28441744
TI  - Production of Laccase by a New Myrothecium verrucaria MD-R-16 Isolated from
      Pigeon Pea [Cajanus cajan (L.) Millsp.] and its Application on Dye
      Decolorization.
AB  - The present study was conducted to screen a laccase-producing fungal endophyte,
      optimize fermentation conditions, and evaluate the decolorization ability of the
      laccase. A new fungal endophyte capable of laccase-producing was firstly isolated
      from pigeon pea and identified as Myrothecium verrucaria based on a ITS-rRNA
      sequences analysis. Meanwhile, various fermentation parameters on the laccase
      production were optimized via response surface methodology (RSM). The optimal
      fermentation conditions were a fermentation time of five days, temperature 30 
      degrees C and pH 6.22. Laccase activity reached 16.52 +/- 0.18 U/mL under the
      above conditions. Furthermore, the laccase showed effective decolorization
      capability toward synthetic dyes (Congo red, Methyl orange, Methyl red, and
      Crystal violet) in the presence of the redox mediator ABTS, with more than 70% of
      dyes decolorizing after 24 h of incubation. Additionally, the activity of laccase
      was relatively stable with pH (4.5-6.5) and a temperature range of 35-55  degrees
      C. Therefore, the high laccase production of the strain and the new fungal
      laccase could provide a promising alterative approach for industrial and
      environmental applications.

PMID- 28441741
TI  - Peptides, Peptidomimetics, and Polypeptides from Marine Sources: A Wealth of
      Natural Sources for Pharmaceutical Applications.
AB  - Nature provides a variety of peptides that are expressed in most living species.
      Evolutionary pressure and natural selection have created and optimized these
      peptides to bind to receptors with high affinity. Hence, natural resources
      provide an abundant chemical space to be explored in peptide-based drug
      discovery. Marine peptides can be extracted by simple solvent extraction
      techniques. The advancement of analytical techniques has made it possible to
      obtain pure peptides from natural resources. Extracted peptides have been
      evaluated as possible therapeutic agents for a wide range of diseases, including
      antibacterial, antifungal, antidiabetic and anticancer activity as well as
      cardiovascular and neurotoxin activity. Although marine resources provide
      thousands of possible peptides, only a few peptides derived from marine sources
      have reached the pharmaceutical market. This review focuses on some of the
      peptides derived from marine sources in the past ten years and gives a brief
      review of those that are currently in clinical trials or on the market.

PMID- 28441745
TI  - Breast Cancer Screening Programmes across the WHO European Region: Differences
      among Countries Based on National Income Level.
AB  - Breast cancer (BC) is the most frequent tumour affecting women all over the
      world. In low- and middle-income countries, where its incidence is expected to
      rise further, BC seems set to become a public health emergency. The aim of the
      present study is to provide a systematic review of current BC screening
      programmes in WHO European Region to identify possible patterns. Multiple
      correspondence analysis was performed to evaluate the association among: measures
      of occurrence; GNI level; type of BC screening programme; organization of public
      information and awareness campaigns regarding primary prevention of modifiable
      risk factors; type of BC screening services; year of screening institution;
      screening coverage and data quality. A key difference between High Income (HI)
      and Low and Middle Income (LMI) States, emerging from the present data, is that
      in the former screening programmes are well organized, with approved screening
      centres, the presence of mobile units to increase coverage, the offer of
      screening tests free of charge; the fairly high quality of occurrence data based
      on high-quality sources, and the adoption of accurate methods to estimate
      incidence and mortality. In conclusion, the governments of LMI countries should
      allocate sufficient resources to increase screening participation and they should
      improve the accuracy of incidence and mortality rates.

PMID- 28441746
TI  - High-Performance Prediction of Human Estrogen Receptor Agonists Based on Chemical
      Structures.
AB  - Many agonists for the estrogen receptor are known to disrupt endocrine
      functioning. We have developed a computational model that predicts agonists for
      the estrogen receptor ligand-binding domain in an assay system. Our model was
      entered into the Tox21 Data Challenge 2014, a computational toxicology
      competition organized by the National Center for Advancing Translational
      Sciences. This competition aims to find high-performance predictive models for
      various adverse-outcome pathways, including the estrogen receptor. Our predictive
      model, which is based on the random forest method, delivered the best performance
      in its competition category. In the current study, the predictive performance of
      the random forest models was improved by strictly adjusting the hyperparameters
      to avoid overfitting. The random forest models were optimized from 4000
      descriptors simultaneously applied to 10,000 activity assay results for the
      estrogen receptor ligand-binding domain, which have been measured and compiled by
      Tox21. Owing to the correlation between our model's and the challenge's results,
      we consider that our model currently possesses the highest predictive power on
      agonist activity of the estrogen receptor ligand-binding domain. Furthermore,
      analysis of the optimized model revealed some important features of the agonists,
      such as the number of hydroxyl groups in the molecules.

PMID- 28441748
TI  - Convergent Validity of a Wearable Sensor System for Measuring Sub-Task
      Performance during the Timed Up-and-Go Test.
AB  - BACKGROUND: The timed-up-and-go test (TUG) is one of the most commonly used tests
      of physical function in clinical practice and for research outcomes. Inertial
      sensors have been used to parse the TUG test into its composite phases (rising,
      walking, turning, etc.), but have not validated this approach against an
      optoelectronic gold-standard, and to our knowledge no studies have published the
      minimal detectable change of these measurements. METHODS: Eleven adults performed
      the TUG three times each under normal and slow walking conditions, and 3 m and 5
      m walking distances, in a 12-camera motion analysis laboratory. An inertial
      measurement unit (IMU) with tri-axial accelerometers and gyroscopes was worn on
      the upper-torso. Motion analysis marker data and IMU signals were analyzed
      separately to identify the six main TUG phases: sit-to-stand, 1st walk, 1st turn,
      2nd walk, 2nd turn, and stand-to-sit, and the absolute agreement between two
      systems analyzed using intra-class correlation (ICC, model 2) analysis. The
      minimal detectable change (MDC) within subjects was also calculated for each TUG
      phase. RESULTS: The overall difference between TUG sub-tasks determined using 3D
      motion capture data and the IMU sensor data was <0.5 s. For all TUG distances and
      speeds, the absolute agreement was high for total TUG time and walk times (ICC >
      0.90), but less for chair activity (ICC range 0.5-0.9) and typically poor for the
      turn time (ICC < 0.4). MDC values for total TUG time ranged between 2-4 s or 12
      22% of the TUG time measurement. MDC of the sub-task times were higher
      proportionally, being 20-60% of the sub-task duration. CONCLUSIONS: We conclude
      that a commercial IMU can be used for quantifying the TUG phases with accuracy
      sufficient for clinical applications; however, the MDC when using inertial
      sensors is not necessarily improved over less sophisticated measurement tools.

PMID- 28441747
TI  - Associations between Diet and Toenail Arsenic Concentration among Pregnant Women
      in Bangladesh: A Prospective Study.
AB  - This prospective study evaluated the relationship between long-term dietary
      habits and total arsenic (As) concentration in toenail clippings in a cohort of
      1616 pregnant women in the Bangladeshi administrative regions of Sirajdikhan and
      Pabna Sadar. Diet was assessed at Gestation Week 28 and at Postpartum Month 1,
      using a locally-validated dish-based semi-quantitative food-frequency
      questionnaire. Toenail As concentration was analyzed by microwave-assisted acid
      digestion and inductively coupled plasma mass spectrometry. Associations between
      natural log-transformed consumption of individual food items and temporally
      matched natural log-transformed toenail As concentration were quantified using
      general linear models that accounted for As concentration in the primary drinking
      water source and other potential confounders. The analysis was stratified by As
      in drinking water (<=50 MUg/L versus >50 MUg/L) and the time of dietary
      assessment (Gestation Week 28 versus Postpartum Week 1). Interestingly, toenail
      As was not significantly associated with consumption of plain rice as
      hypothesized. However, toenail As was positively associated with consumption of
      several vegetable, fish and meat items and was negatively associated with
      consumption of rice, cereal, fruits, and milk based food items. Further studies
      in pregnant women are needed to compare As metabolism at different levels of As
      exposure and the interaction between dietary composition and As absorption.

PMID- 28441749
TI  - Using Wavelet Packet Transform for Surface Roughness Evaluation and Texture
      Extraction.
AB  - Surface characterization plays a significant role in evaluating surface
      functional performance. In this paper, we introduce wavelet packet transform for
      surface roughness characterization and surface texture extraction. Surface
      topography is acquired by a confocal laser scanning microscope. Smooth border
      padding and de-noise process are implemented to generate a roughness surface
      precisely. By analyzing the high frequency components of a simulated profile,
      surface textures are separated by using wavelet packet transform, and the
      reconstructed roughness and waviness coincide well with the original ones.
      Wavelet packet transform is then used as a smooth filter for texture extraction.
      A roughness specimen and three real engineering surfaces are also analyzed in
      detail. Profile and areal roughness parameters are calculated to quantify the
      characterization results and compared with those measured by a profile meter.
      Most obtained roughness parameters agree well with the measurement results, and
      the largest deviation occurs in the skewness. The relations between the roughness
      parameters and noise are analyzed by simulation for explaining the relatively
      large deviations. The extracted textures reflect the surface structure and
      indicate the manufacturing conditions well, which is helpful for further feature
      recognition and matching. By using wavelet packet transform, engineering surfaces
      are comprehensively characterized including evaluating surface roughness and
      extracting surface texture.

PMID- 28441751
TI  - Implementation Issues of Adaptive Energy Detection in Heterogeneous Wireless
      Networks.
AB  - Spectrum sensing (SS) enables the coexistence of non-coordinated heterogeneous
      wireless systems operating in the same band. Due to its computational simplicity,
      energy detection (ED) technique has been widespread employed in SS applications;
      nonetheless, the conventional ED may be unreliable under environmental
      impairments, justifying the use of ED-based variants. Assessing ED algorithms
      from theoretical and simulation viewpoints relies on several assumptions and
      simplifications which, eventually, lead to conclusions that do not necessarily
      meet the requirements imposed by real propagation environments. This work
      addresses those problems by dealing with practical implementation issues of
      adaptive least mean square (LMS)-based ED algorithms. The paper proposes a new
      adaptive ED algorithm that uses a variable step-size guaranteeing the LMS
      convergence in time-varying environments. Several implementation guidelines are
      provided and, additionally, an empirical assessment and validation with a
      software defined radio-based hardware is carried out. Experimental results show
      good performance in terms of probabilities of detection ( P d > 0 . 9 ) and false
      alarm ( P f ~ 0 . 05 ) in a range of low signal-to-noise ratios around [ - 4 , 1
      ] dB, in both single-node and cooperative modes. The proposed sensing methodology
      enables a seamless monitoring of the radio electromagnetic spectrum in order to
      provide band occupancy information for an efficient usage among several wireless
      communications systems.

PMID- 28441752
TI  - Photocatalytic and Adsorption Performances of Faceted Cuprous Oxide (Cu2O)
      Particles for the Removal of Methyl Orange (MO) from Aqueous Media.
AB  - Particles of sub-micron size possess significant capacity to adsorb organic
      molecules from aqueous media. Semiconductor photocatalysts in particle form could
      potentially be utilized for dye removal through either physical adsorption or
      photo-induced chemical process. The photocatalytic and adsorption capabilities of
      Cu2O particles with various exposed crystal facets have been studied through
      separate adsorption capacity test and photocatalytic degradation test. These
      crystals display unique cubic, octahedral, rhombic dodecahedral, and truncated
      polyhedral shapes due to specifically exposed crystal facet(s). For comparison,
      Cu2O particles with no clear exposed facets were also prepared. The current work
      confirms that the surface charge critically affects the adsorption performance of
      the synthesized Cu2O particles. The octahedral shaped Cu2O particles, with
      exposed {111} facets, possess the best adsorption capability of methyl orange
      (MO) dye due to the strongest positive surface charge among the different types
      of particles. In addition, we also found that the adsorption of MO follows the
      Langmuir monolayer mechanism. The octahedral particles also performed the best in
      photocatalytic dye degradation of MO under visible light irradiation because of
      the assistance from dye absorption. On top of the photocatalytic study, the
      stability of these Cu2O particles during the photocatalytic processes was also
      investigated. Cu(OH)2 and CuO are the likely corrosion products found on the
      particle surface after the photocorrosion in MO solution. By adding hole
      scavengers in the solution, the photocorrosion of Cu2O was greatly reduced. This
      observation confirms that the photocatalytically generated holes were responsible
      for the photocorrosion of Cu2O.

PMID- 28441750
TI  - Adenosine A1 and A2A Receptors in the Brain: Current Research and Their Role in
      Neurodegeneration.
AB  - The inhibitory adenosine A1 receptor (A1R) and excitatory A2A receptor (A2AR) are
      predominantly expressed in the brain. Whereas the A2AR has been implicated in
      normal aging and enhancing neurotoxicity in multiple neurodegenerative diseases,
      the inhibitory A1R has traditionally been ascribed to have a neuroprotective
      function in various brain insults. This review provides a summary of the emerging
      role of prolonged A1R signaling and its potential cross-talk with A2AR in the
      cellular basis for increased neurotoxicity in neurodegenerative disorders. This
      A1R signaling enhances A2AR-mediated neurodegeneration, and provides a platform
      for future development of neuroprotective agents in stroke, Parkinson's disease
      and epilepsy.

PMID- 28441754
TI  - Improved Line Tracing Methods for Removal of Bad Streaks Noise in CCD Line Array
      Image-A Case Study with GF-1 Images.
AB  - Remote sensing images could provide us with tremendous quantities of large-scale
      information. Noise artifacts (stripes), however, made the images inappropriate
      for vitalization and batch process. An effective restoration method would make
      images ready for further analysis. In this paper, a new method is proposed to
      correct the stripes and bad abnormal pixels in charge-coupled device (CCD) linear
      array images. The method involved a line tracing method, limiting the location of
      noise to a rectangular region, and corrected abnormal pixels with the Lagrange
      polynomial algorithm. The proposed detection and restoration method were applied
      to Gaofen-1 satellite (GF-1) images, and the performance of this method was
      evaluated by omission ratio and false detection ratio, which reached 0.6% and 0%,
      respectively. This method saved 55.9% of the time, compared with traditional
      method.

PMID- 28441753
TI  - CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI) Toxicity.
AB  - To investigate the toxic mechanism of hexavalent chromium Cr(VI) and search for
      an antidote for Cr(VI)-induced cytotoxicity, a study of mitochondrial dysfunction
      induced by Cr(VI) and cell survival by recovering mitochondrial function was
      performed. In the present study, we found that the gene expression of electron
      transfer flavoprotein dehydrogenase (ETFDH) was strongly downregulated by Cr(VI)
      exposure. The levels of coenzyme 10 (CoQ10) and mitochondrial biogenesis
      presented by mitochondrial mass and mitochondrial DNA copy number were also
      significantly reduced after Cr(VI) exposure. The subsequent, Cr(VI)-induced
      mitochondrial damage and apoptosis were characterized by reactive oxygen species
      (ROS) accumulation, caspase-3 and caspase-9 activation, decreased superoxide
      dismutase (SOD) and ATP production, increased methane dicarboxylic aldehyde (MDA)
      content, mitochondrial membrane depolarization and mitochondrial permeability
      transition pore (MPTP) opening, increased Ca2+ levels, Cyt c release, decreased
      Bcl-2 expression, and significantly elevated Bax expression. The Cr(VI)-induced
      deleterious changes were attenuated by pretreatment with CoQ10 in L-02
      hepatocytes. These data suggest that Cr(VI) induces CoQ10 deficiency in L-02
      hepatocytes, indicating that this deficiency may be a biomarker of mitochondrial
      dysfunction in Cr(VI) poisoning and that exogenous administration of CoQ10 may
      restore mitochondrial function and protect the liver from Cr(VI) exposure.

PMID- 28441755
TI  - Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for
      Cartilage and Bone Regeneration.
AB  - Advances in mesenchymal stem cells (MSCs) and cell replacement therapies are
      promising approaches to treat cartilage and bone defects since substantial
      differentiation capacities of MSCs match the demands of tissue regeneration. Our
      understanding of the dynamic process requiring indispensable differentiation of
      MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched
      in brain) regulating gene signature for differentiation of human adipose derived
      mesenchymal stem cells (ASCs) into chondrogenic, osteogenic, and adipogenic
      lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB
      enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation
      of SOX9 with concomitant increase in glycosaminoglycans (GAGs), and type II
      collagen (COL2). RHEB increases the osteogenesis via upregulation of runt related
      transcription factor 2 (RUNX2) with an increase in the calcium and phosphate
      contents. RHEB also increases the expression of osteogenic markers, osteonectin
      and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY
      (Sex determining region Y)-box 9 (SOX9) and RUNX2, and therefore had decreased
      chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs
      differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer
      binding protein beta (C/EBPbeta). Conversely, RHEB knockdown abolished the
      negative regulation of adipogenesis. We demonstrate that RHEB is a novel
      regulator, with a critical role in ASCs lineage determination, and RHEB-modulated
      ASCs may be useful as a cell therapy for cartilage and bone defect treatments.

PMID- 28441756
TI  - The Interactions between ZnO Nanoparticles (NPs) and alpha-Linolenic Acid (LNA)
      Complexed to BSA Did Not Influence the Toxicity of ZnO NPs on HepG2 Cells.
AB  - BACKGROUND: Nanoparticles (NPs) entering the biological environment could
      interact with biomolecules, but little is known about the interaction between
      unsaturated fatty acids (UFA) and NPs. METHODS: This study used alpha-linolenic
      acid (LNA) complexed to bovine serum albumin (BSA) for UFA and HepG2 cells for
      hepatocytes. The interactions between BSA or LNA and ZnO NPs were studied.
      RESULTS: The presence of BSA or LNA affected the hydrodynamic size, zeta
      potential, UV-Vis, fluorescence, and synchronous fluorescence spectra of ZnO NPs,
      which indicated an interaction between BSA or LNA and NPs. Exposure to ZnO NPs
      with the presence of BSA significantly induced the damage to mitochondria and
      lysosomes in HepG2 cells, associated with an increase of intracellular Zn ions,
      but not intracellular superoxide. Paradoxically, the release of inflammatory
      cytokine interleukin-6 (IL-6) was decreased, which indicated the anti
      inflammatory effects of ZnO NPs when BSA was present. The presence of LNA did not
      significantly affect all of these endpoints in HepG2 cells exposed to ZnO NPs and
      BSA. CONCLUSIONS: the results from the present study indicated that BSA-complexed
      LNA might modestly interact with ZnO NPs, but did not significantly affect ZnO
      NPs and BSA-induced biological effects in HepG2 cells.

PMID- 28441757
TI  - Correction: Ruiz, E. et al. Emerging Interaction Patterns in the Emiliania
      Huxleyi-EhV System. Viruses 2016, 9, 61.
AB  - n/a.

PMID- 28441758
TI  - Acteoside and Isoacteoside Protect Amyloid beta Peptide Induced Cytotoxicity,
      Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo.
AB  - Acteoside and isoacteoside, two phenylethanoid glycosides, coexist in some
      plants. This study investigates the memory-improving and cytoprotective effects
      of acteoside and isoacteoside in amyloid beta peptide 1-42 (Abeta 1-42)-infused
      rats and Abeta 1-42-treated SH-SY5Y cells. It further elucidates the role of
      amyloid cascade and central neuronal function in these effects. Acteoside and
      isoacteoside ameliorated cognitive deficits, decreased amyloid deposition, and
      reversed central cholinergic dysfunction that were caused by Abeta 1-42 in rats.
      Acteoside and isoacteoside further decreased extracellular Abeta 1-40 production
      and restored the cell viability that was decreased by Abeta 1-42 in SH-SY5Y
      cells. Acteoside and isoacteoside also promoted Abeta 1-40 degradation and
      inhibited Abeta 1-42 oligomerization in vitro. However, the memory-improving and
      cytoprotective effects of isoacteoside exceeded those of acteoside. Isoacteoside
      promoted exploratory behavior and restored cortical and hippocampal dopamine
      levels, but acteoside did not. We suggest that acteoside and isoacteoside
      ameliorated the cognitive dysfunction that was caused by Abeta 1-42 by blocking
      amyloid deposition via preventing amyloid oligomerization, and reversing central
      neuronal function via counteracting amyloid cytotoxicity.

PMID- 28441759
TI  - Synaptic Homeostasis and Its Immunological Disturbance in Neuromuscular Junction
      Disorders.
AB  - In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor
      (nAChR) clustering, trans-synaptic communication and synaptic stabilization are
      modulated by the molecular mechanisms underlying synaptic plasticity. The
      synaptic functions are based presynaptically on the active zone architecture,
      synaptic vesicle proteins, Ca2+ channels and synaptic vesicle recycling.
      Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized
      sensitivity to ACh, and synaptic stabilization via linkage to the extracellular
      matrix so as to be precisely opposed to the nerve terminal. Focusing on neural
      agrin, Wnts, muscle-specific tyrosine kinase (a mediator of agrin and Wnts
      signalings and regulator of trans-synaptic communication), low-density
      lipoprotein receptor-related protein 4 (the receptor of agrin and Wnts and
      participant in retrograde signaling), laminin-network (including muscle-derived
      agrin), extracellular matrix proteins (participating in the synaptic
      stabilization) and presynaptic receptors (including muscarinic and adenosine
      receptors), we review the functional structures of the synapse by making
      reference to immunological pathogenecities in postsynaptic disease, myasthenia
      gravis. The synapse-related proteins including cortactin, coronin-6, caveolin-3,
      doublecortin, R-spondin 2, amyloid precursor family proteins, glia cell-derived
      neurotrophic factor and neurexins are also discussed in terms of their possible
      contribution to efficient synaptic transmission at the neuromuscular junction.

PMID- 28441760
TI  - Supplementation with a Polyphenol-Rich Extract, PerfLoad(r), Improves Physical
      Performance during High-Intensity Exercise: A Randomized, Double Blind, Crossover
      Trial.
AB  - Workout capacity is energy-production driven. To produce peak metabolic power
      outputs, the organism predominantly relies more on anaerobic metabolism, but this
      undoubtedly has a negative and limiting impact on muscle function and
      performance. The aim of the study was to evaluate if an innovative polyphenol
      based food supplement, PerfLoad(r), was able to improve metabolic homeostasis and
      physical performance during high-intensity exercises under anaerobic conditions.
      The effect of a supplementation has been investigated on fifteen recreationally
      active male athletes during a randomized, double-blind and crossover clinical
      investigation. The Wingate test, an inducer of an unbalanced metabolism
      associated to oxidative stress, was used to assess maximum anaerobic power during
      a high-intensity exercise on a cycle ergometer. Supplementation with PerfLoad(r)
      correlated with a significant increase in total power output (5%), maximal peak
      power output (3.7%), and average power developed (5%), without inducing more
      fatigue or greater heart rate. Instead, oxidative homeostasis was stabilized in
      supplemented subjects. Such results demonstrated that PerfLoad(r) is a natural
      and efficient solution capable of, similarly to training benefits, helping
      athletes to improve their physical performance, while balancing their metabolism
      and reducing exercise-induced oxidative stress.

PMID- 28441761
TI  - E2/ER beta Enhances Calcineurin Protein Degradation and PI3K/Akt/MDM2 Signal
      Transduction to Inhibit ISO-Induced Myocardial Cell Apoptosis.
AB  - Secretion of multifunctional estrogen and its receptor has been widely considered
      as the reason for markedly higher frequency of heart disease in men than in
      women. 17beta-Estradiol (E2), for instance, has been reported to prevent
      development of cardiac apoptosis via activation of estrogen receptors (ERs). In
      addition, protein phosphatase such as protein phosphatase 1 (PP1) and calcineurin
      (PP2B) are also involved in cardiac hypertrophy and cell apoptosis signaling.
      However, the mechanism by which E2/ERbeta suppresses apoptosis is not fully
      understood, and the role of protein phosphatase in E2/ERbeta action also needs
      further investigation. In this study, we observed that E2/ERbeta inhibited
      isoproterenol (ISO)-induced myocardial cell apoptosis, cytochrome c release and
      downstream apoptotic markers. Moreover, we found that E2/ERbeta blocks ISO
      induced apoptosis in H9c2 cells through the enhancement of calcineurin protein
      degradation through PI3K/Akt/MDM2 signaling pathway. Our results suggest that
      supplementation with estrogen and/or overexpression of estrogen receptor beta
      gene may prove to be effective means to treat stress-induced myocardial damage.

PMID- 28441762
TI  - Replication and Oncolytic Activity of an Avian Orthoreovirus in Human
      Hepatocellular Carcinoma Cells.
AB  - Oncolytic viruses are cancer therapeutics with promising outcomes in pre-clinical
      and clinical settings. Animal viruses have the possibility to avoid pre-existing
      immunity in humans, while being safe and immunostimulatory. We isolated an avian
      orthoreovirus (ARV-PB1), and tested it against a panel of hepatocellular
      carcinoma cells. We found that ARV-PB1 replicated well and induced strong
      cytopathic effects. It was determined that one mechanism of cell death was
      through syncytia formation, resulting in apoptosis and induction of interferon
      stimulated genes (ISGs). As hepatitis C virus (HCV) is a major cause of
      hepatocellular carcinoma worldwide, we investigated the effect of ARV-PB1 against
      cells already infected with this virus. Both HCV replicon-containing and infected
      cells supported ARV-PB1 replication and underwent cytolysis. Finally, we
      generated in silico models to compare the structures of human reovirus- and ARV
      PB1-derived S1 proteins, which are the primary targets of neutralizing
      antibodies. Tertiary alignments confirmed that ARV-PB1 differs from its human
      homolog, suggesting that immunity to human reoviruses would not be a barrier to
      its use. Therefore, ARV-PB1 can potentially expand the repertoire of oncolytic
      viruses for treatment of human hepatocellular carcinoma and other malignancies.

PMID- 28441763
TI  - Improving Passive Time Reversal Underwater Acoustic Communications Using Subarray
      Processing.
AB  - Multichannel receivers are usually employed in high-rate underwater acoustic
      communication to achieve spatial diversity. In the context of multichannel
      underwater acoustic communications, passive time reversal (TR) combined with a
      single-channel adaptive decision feedback equalizer (TR-DFE) is a low-complexity
      solution to achieve both spatial and temporal focusing. In this paper, we present
      a novel receiver structure to combine passive time reversal with a low-order
      multichannel adaptive decision feedback equalizer (TR-MC-DFE) to improve the
      performance of the conventional TR-DFE. First, the proposed method divides the
      whole received array into several subarrays. Second, we conduct passive time
      reversal processing in each subarray. Third, the multiple subarray outputs are
      equalized with a low-order multichannel DFE. We also investigated different
      channel estimation methods, including least squares (LS), orthogonal matching
      pursuit (OMP), and improved proportionate normalized least mean squares (IPNLMS).
      The bit error rate (BER) and output signal-to-noise ratio (SNR) performances of
      the receiver algorithms are evaluated using simulation and real data collected in
      a lake experiment. The source-receiver range is 7.4 km, and the data rate with
      quadrature phase shift keying (QPSK) signal is 8 kbits/s. The uncoded BER of the
      single input multiple output (SIMO) systems varies between 1 * 10 - 1 and 2 * 10 
      2 for the conventional TR-DFE, and between 1 * 10 - 2 and 1 * 10 - 3 for the
      proposed TR-MC-DFE when eight hydrophones are utilized. Compared to conventional
      TR-DFE, the average output SNR of the experimental data is enhanced by 3 dB.

PMID- 28441764
TI  - Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical
      Exposure Is Visualised by Stimulated Raman Scattering Microscopy.
AB  - Early life stage exposure to environmental chemicals may play a role in obesity
      by altering adipogenesis; however, robust in vivo methods to quantify these
      effects are lacking. The goal of this study was to analyze the effects of
      developmental exposure to chemicals on adipogenesis in the zebrafish (Danio
      rerio). We used label-free Stimulated Raman Scattering (SRS) microscopy for the
      first time to image zebrafish adipogenesis at 15 days post fertilization (dpf)
      and compared standard feed conditions (StF) to a high fat diet (HFD) or high
      glucose diet (HGD). We also exposed zebrafish embryos to a non-toxic
      concentration of tributyltin (TBT, 1 nM) or Tris(1,3-dichloroisopropyl)phosphate
      (TDCiPP, 0.5 uM) from 0-6 dpf and reared larvae to 15 dpf under StF. Potential
      molecular mechanisms of altered adipogenesis were examined by qPCR. Diet
      dependent modulation of adipogenesis was observed, with HFD resulting in a
      threefold increase in larvae with adipocytes, compared to StF and HGD.
      Developmental exposure to TBT but not TDCiPP significantly increased adipocyte
      differentiation. The expression of adipogenic genes such as pparda, lxr and lepa
      was altered in response to HFD or chemicals. This study shows that SRS microscopy
      can be successfully applied to zebrafish to visualize and quantify adipogenesis,
      and is a powerful approach for identifying obesogenic chemicals in vivo.

PMID- 28441765
TI  - Distinct Fiber Type Signature in Mouse Muscles Expressing a Mutant Lamin A
      Responsible for Congenital Muscular Dystrophy in a Patient.
AB  - Specific mutations in LMNA, which encodes nuclear intermediate filament proteins
      lamins A/C, affect skeletal muscle tissues. Early-onset LMNA myopathies reveal
      different alterations of muscle fibers, including fiber type disproportion or
      prominent dystrophic and/or inflammatory changes. Recently, we identified the
      p.R388P LMNA mutation as responsible for congenital muscular dystrophy (L-CMD)
      and lipodystrophy. Here, we asked whether viral-mediated expression of mutant
      lamin A in murine skeletal muscles would be a pertinent model to reveal specific
      muscle alterations. We found that the total amount and size of muscle fibers as
      well as the extent of either inflammation or muscle regeneration were similar to
      wildtype or mutant lamin A. In contrast, the amount of fast oxidative muscle
      fibers containing myosin heavy chain IIA was lower upon expression of mutant
      lamin A, in correlation with lower expression of genes encoding transcription
      factors MEF2C and MyoD. These data validate this in vivo model for highlighting
      distinct muscle phenotypes associated with different lamin contexts.
      Additionally, the data suggest that alteration of muscle fiber type identity may
      contribute to the mechanisms underlying physiopathology of L-CMD related to R388P
      mutant lamin A.

PMID- 28441766
TI  - Fat Mass Is Positively Associated with Estimated Hip Bone Strength among Chinese
      Men Aged 50 Years and above with Low Levels of Lean Mass.
AB  - This study investigated the relationships of fat mass (FM) and lean mass (LM)
      with estimated hip bone strength in Chinese men aged 50-80 years (median value:
      62.0 years). A cross-sectional study including 889 men was conducted in
      Guangzhou, China. Body composition and hip bone parameters were generated by dual
      energy X-ray absorptiometry (DXA). The relationships of the LM index (LMI) and
      the FM index (FMI) with bone phenotypes were detected by generalised additive
      models and multiple linear regression. The associations between the FMI and the
      bone variables in LMI tertiles were further analysed. The FMI possessed a linear
      relationship with greater estimated hip bone strength after adjustment for the
      potential confounders (p < 0.05). Linear relationships were also observed for the
      LMI with most bone phenotypes, except for the cross-sectional area (p < 0.05).
      The contribution of the LMI (4.0%-12.8%) was greater than that of the FMI (2.0%
      5.7%). The associations between the FMI and bone phenotypes became weaker after
      controlling for LMI. Further analyses showed that estimated bone strength
      ascended with FMI in the lowest LMI tertile (p < 0.05), but not in the subgroups
      with a higher LMI. This study suggested that LM played a critical role in bone
      health in middle-aged and elderly Chinese men, and that the maintenance of
      adequate FM could help to promote bone acquisition in relatively thin men.

PMID- 28441767
TI  - Inhibitory Effect of Triterpenoids from Panax ginseng on Coagulation Factor X.
AB  - Enzymes involved in the coagulation process have received great attention as
      potential targets for the development of oral anti-coagulants. Among these
      enzymes, coagulation factor Xa (FXa) has remained the center of attention in the
      last decade. In this study, 16 ginsenosides and two sapogenins were isolated,
      identified and quantified. To determine the inhibitory potential on FXa, the
      chromogenic substrates method was used. The assay suggested that compounds 5, 13
      and 18 were mainly responsible for the anti-coagulant effect. Furthermore, these
      three compounds also possessed high thrombin selectivity in the thrombin
      inhibition assay. Furthermore, Glide XP from Schrodinger was employed for
      molecular docking to clarify the interaction between the bioactive compounds and
      FXa. Therefore, the chemical and biological results indicate that compounds 5
      (ginsenoside Rg2), 13 (ginsenoside Rg3) and 18 (protopanaxtriol, PPT) are
      potential natural inhibitors against FXa.

PMID- 28441768
TI  - Probabilistic Fatigue Life Updating for Railway Bridges Based on Local Inspection
      and Repair.
AB  - Railway bridges are exposed to repeated train loads, which may cause fatigue
      failure. As critical links in a transportation network, railway bridges are
      expected to survive for a target period of time, but sometimes they fail earlier
      than expected. To guarantee the target bridge life, bridge maintenance activities
      such as local inspection and repair should be undertaken properly. However, this
      is a challenging task because there are various sources of uncertainty associated
      with aging bridges, train loads, environmental conditions, and maintenance work.
      Therefore, to perform optimal risk-based maintenance of railway bridges, it is
      essential to estimate the probabilistic fatigue life of a railway bridge and
      update the life information based on the results of local inspections and repair.
      Recently, a system reliability approach was proposed to evaluate the fatigue
      failure risk of structural systems and update the prior risk information in
      various inspection scenarios. However, this approach can handle only a constant
      amplitude load and has limitations in considering a cyclic load with varying
      amplitude levels, which is the major loading pattern generated by train traffic.
      In addition, it is not feasible to update the prior risk information after
      bridges are repaired. In this research, the system reliability approach is
      further developed so that it can handle a varying-amplitude load and update the
      system-level risk of fatigue failure for railway bridges after inspection and
      repair. The proposed method is applied to a numerical example of an in-service
      railway bridge, and the effects of inspection and repair on the probabilistic
      fatigue life are discussed.

PMID- 28441769
TI  - UVA, UVB and UVC Light Enhances the Biosynthesis of Phenolic Antioxidants in
      Fresh-Cut Carrot through a Synergistic Effect with Wounding.
AB  - Previously, we found that phenolic content and antioxidant capacity (AOX) in
      carrots increased with wounding intensity. It was also reported that UV radiation
      may trigger the phenylpropanoid metabolism in plant tissues. Here, we determined
      the combined effect of wounding intensity and UV radiation on phenolic compounds,
      AOX, and the phenylalanine ammonia-lyase (PAL) activity of carrots. Accordingly,
      phenolic content, AOX, and PAL activity increased in cut carrots with the
      duration of UVC radiation, whereas whole carrots showed no increase. Carrot pies
      showed a higher increase compared to slices and shreds. Phenolics, AOX, and PAL
      activity also increased in cut carrots exposed to UVA or UVB. The major phenolics
      were chlorogenic acid and its isomers, ferulic acid, and isocoumarin. The type of
      UV radiation affected phenolic profiles. Chlorogenic acid was induced by all UV
      radiations but mostly by UVB and UVC, ferulic acid was induced by all UV lights
      to comparable levels, while isocoumarin and 4,5-diCQA was induced mainly by UVB
      and UVC compared to UVA. In general, total phenolics correlated linearly with AOX
      for all treatments. A reactive oxygen species (ROS) mediated hypothetical
      mechanism explaining the synergistic effect of wounding and different UV
      radiation stresses on phenolics accumulation in plants is herein proposed.

PMID- 28441770
TI  - Direction of Arrival Estimation for MIMO Radar via Unitary Nuclear Norm
      Minimization.
AB  - In this paper, we consider the direction of arrival (DOA) estimation issue of
      noncircular (NC) source in multiple-input multiple-output (MIMO) radar and
      propose a novel unitary nuclear norm minimization (UNNM) algorithm. In the
      proposed method, the noncircular properties of signals are used to double the
      virtual array aperture, and the real-valued data are obtained by utilizing
      unitary transformation. Then a real-valued block sparse model is established
      based on a novel over-complete dictionary, and a UNNM algorithm is formulated for
      recovering the block-sparse matrix. In addition, the real-valued NC-MUSIC
      spectrum is used to design a weight matrix for reweighting the nuclear norm
      minimization to achieve the enhanced sparsity of solutions. Finally, the DOA is
      estimated by searching the non-zero blocks of the recovered matrix. Because of
      using the noncircular properties of signals to extend the virtual array aperture
      and an additional real structure to suppress the noise, the proposed method
      provides better performance compared with the conventional sparse recovery based
      algorithms. Furthermore, the proposed method can handle the case of
      underdetermined DOA estimation. Simulation results show the effectiveness and
      advantages of the proposed method.

PMID- 28441771
TI  - Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications
      for Treatment.
AB  - Aberrant signaling of the hepatocyte growth factor (HGF)/c-Met pathway has been
      identified as a promoter of tumorigenesis in several tumor types including head
      and neck squamous cell carcinoma (HNSCC). Despite a relatively low c-Met mutation
      frequency, overexpression of HGF and its receptor c-Met has been observed in more
      than 80% of HNSCC tumors, with preclinical and clinical studies linking
      overexpression with cellular proliferation, invasion, migration, and poor
      prognosis. c-Met is activated by HGF through a paracrine mechanism to promote
      cellular morphogenesis enabling cells to acquire mesenchymal phenotypes in part
      through the epithelial-mesenchymal transition, contributing to metastasis. The
      HGF/c-Met pathway may also act as a resistance mechanism against epidermal growth
      factor receptor (EGFR) inhibition in advanced HNSCC. Furthermore, with the
      identification of a biologically distinct subset of HNSCC tumors acquired from
      human papillomavirus (HPV) infection that generally portends a good prognosis,
      high expression of HGF or c-Met in HPV-negative tumors has been associated with
      worse prognosis. Dysregulated HGF/c-Met signaling results in an aggressive HNSCC
      phenotype which has led to clinical investigations for targeted inhibition of
      this pathway. In this review, HGF/c-Met signaling, pathway alterations,
      associations with clinical outcomes, and preclinical and clinical therapeutic
      strategies for targeting HGF/c-Met signaling in HNSCC are discussed.

PMID- 28441773
TI  - Overview of Four Functional Classification Systems Commonly Used in Cerebral
      Palsy.
AB  - Cerebral palsy (CP) is the most common physical disability in childhood. CP
      comprises a heterogeneous group of disorders that can result in spasticity,
      dystonia, muscle contractures, weakness and coordination difficulty that
      ultimately affects the ability to control movements. Traditionally, CP has been
      classified using a combination of the motor type and the topographical
      distribution, as well as subjective severity level. Imprecise terms such as these
      tell very little about what a person is able to do functionally and can impair
      clear communication between providers. More recently, classification systems have
      been created employing a simple ordinal grading system of functional performance.
      These systems allow a more precise discussion between providers, as well as
      better subject stratification for research. The goal of this review is to
      describe four common functional classification systems for cerebral palsy: the
      Gross Motor Function Classification System (GMFCS), the Manual Ability
      Classification System (MACS), the Communication Function Classification System
      (CFCS), and the Eating and Drinking Ability Classification System (EDACS). These
      measures are all standardized, reliable, and complementary to one another.

PMID- 28441772
TI  - Structural and Biochemical Properties of Novel Self-Cleaving Ribozymes.
AB  - Fourteen well-defined ribozyme classes have been identified to date, among which
      nine are site-specific self-cleaving ribozymes. Very recently, small self
      cleaving ribozymes have attracted renewed interest in their structure,
      biochemistry, and biological function since the discovery, during the last three
      years, of four novel ribozymes, termed twister, twister sister, pistol, and
      hatchet. In this review, we mainly address the structure, biochemistry, and
      catalytic mechanism of the novel ribozymes. They are characterized by distinct
      active site architectures and divergent, but similar, biochemical properties. The
      cleavage activities of the ribozymes are highly dependent upon divalent cations,
      pH, and base-specific mutations, which can cause changes in the nucleotide
      arrangement and/or electrostatic potential around the cleavage site. It is most
      likely that a guanine and adenine in close proximity of the cleavage site are
      involved in general acid-base catalysis. In addition, metal ions appear to play a
      structural rather than catalytic role although some of their crystal structures
      have shown a direct metal ion coordination to a non-bridging phosphate oxygen at
      the cleavage site. Collectively, the structural and biochemical data of the four
      newest ribozymes could contribute to advance our mechanistic understanding of how
      self-cleaving ribozymes accomplish their efficient site-specific RNA cleavages.

PMID- 28441774
TI  - Brain-Derived Neurotrophic Factor Mediated Perfluorooctane Sulfonate Induced
      Neurotoxicity via Epigenetics Regulation in SK-N-SH Cells.
AB  - Perfluorooctane sulfonate (PFOS), a new kind of persistent organic pollutant, is
      widely distributed in the environment and exists in various organisms, where it
      is also a neurotoxic compound. However, the potential mechanism of its
      neurotoxicity is still unclear. To examine the role of epigenetics in the
      neurotoxicity induced by PFOS, SK-N-SH cells were treated with different
      concentrations of PFOS or control medium (0.1% DMSO) for 48 h. The mRNA levels of
      DNA methyltransferases (DNMTs) and Brain-derived neurotrophic factor (BDNF),
      microRNA-16, microRNA-22, and microRNA-30a-5p were detected by Quantitative PCR
      (QPCR). Enzyme Linked Immunosorbent Assay (ELISA) was used to measure the protein
      levels of BDNF, and a western blot was applied to analyze the protein levels of
      DNMTs. Bisulfite sequencing PCR (BSP) was used to detect the methylation status
      of the BDNF promoter I and IV. Results of MTT assays indicated that treatment
      with PFOS could lead to a significant decrease of cell viability, and the treated
      cells became shrunk. In addition, PFOS exposure decreased the expression of BDNF
      at mRNA and protein levels, increased the expression of microRNA-16, microRNA-22,
      microRNA-30a-5p, and decreased the expression of DNMT1 at mRNA and protein
      levels, but increased the expression of DNMT3b at mRNA and protein levels. Our
      results also demonstrate that PFOS exposure changes the methylation status of
      BDNF promoter I and IV. The findings of the present study suggest that
      methylation regulation of BDNF gene promoter and increases of BDNF-related
      microRNA might underlie the mechanisms of PFOS-induced neurotoxicity.

PMID- 28441775
TI  - Progress in the Correlative Atomic Force Microscopy and Optical Microscopy.
AB  - Atomic force microscopy (AFM) has evolved from the originally morphological
      imaging technique to a powerful and multifunctional technique for manipulating
      and detecting the interactions between molecules at nanometer resolution.
      However, AFM cannot provide the precise information of synchronized molecular
      groups and has many shortcomings in the aspects of determining the mechanism of
      the interactions and the elaborate structure due to the limitations of the
      technology, itself, such as non-specificity and low imaging speed. To overcome
      the technical limitations, it is necessary to combine AFM with other
      complementary techniques, such as fluorescence microscopy. The combination of
      several complementary techniques in one instrument has increasingly become a
      vital approach to investigate the details of the interactions among molecules and
      molecular dynamics. In this review, we reported the principles of AFM and optical
      microscopy, such as confocal microscopy and single-molecule localization
      microscopy, and focused on the development and use of correlative AFM and optical
      microscopy.

PMID- 28441776
TI  - Gold Nanoparticles for Modulating Neuronal Behavior.
AB  - Understanding the detailed functioning and pathophysiology of the brain and the
      nervous system continues to challenge the scientific community, particularly in
      terms of scaling up techniques for monitoring and interfacing with complex 3D
      networks. Nanotechnology has the potential to support this scaling up, where the
      eventual goal would be to address individual nerve cells within functional units
      of both the central and peripheral nervous system. Gold nanoparticles provide a
      variety of physical and chemical properties that have attracted attention as a
      light-activated nanoscale neuronal interface. This review provides a critical
      overview of the photothermal and photomechanical properties of chemically
      functionalized gold nanoparticles that have been exploited to trigger a range of
      biological responses in neuronal tissues, including modulation of electrical
      activity and nerve regeneration. The prospects and challenges for further
      development are also discussed.

PMID- 28441777
TI  - Health Effects of Psidium guajava L. Leaves: An Overview of the Last Decade.
AB  - Today, there is increasing interest in discovering new bioactive compounds
      derived from ethnomedicine. Preparations of guava (Psidium guajava L.) leaves
      have traditionally been used to manage several diseases. The pharmacological
      research in vitro as well as in vivo has been widely used to demonstrate the
      potential of the extracts from the leaves for the co-treatment of different
      ailments with high prevalence worldwide, upholding the traditional medicine in
      cases such as diabetes mellitus, cardiovascular diseases, cancer, and parasitic
      infections. Moreover, the biological activity has been attributed to the
      bioactive composition of the leaves, to some specific phytochemical subclasses,
      or even to individual compounds. Phenolic compounds in guava leaves have been
      credited with regulating blood-glucose levels. Thus, the aim of the present
      review was to compile results from in vitro and in vivo studies carried out with
      guava leaves over the last decade, relating the effects to their clinical
      applications in order to focus further research for finding individual bioactive
      compounds. Some food applications (guava tea and supplementary feed for
      aquaculture) and some clinical, in vitro, and in vivo outcomes are also included.

PMID- 28441778
TI  - Gene Expression Analysis before and after Treatment with Adalimumab in Patients
      with Ankylosing Spondylitis Identifies Molecular Pathways Associated with
      Response to Therapy.
AB  - The etiology of Ankylosing spondylitis (AS) is still unknown and the
      identification of the involved molecular pathogenetic pathways is a current
      challenge in the study of the disease. Adalimumab (ADA), an anti-tumor necrosis
      factor (TNF)-alpha agent, is used in the treatment of AS. We aimed at identifying
      pathogenetic pathways modified by ADA in patients with a good response to the
      treatment. Gene expression analysis of Peripheral Blood Cells (PBC) from six
      responders and four not responder patients was performed before and after
      treatment. Differentially expressed genes (DEGs) were submitted to functional
      enrichment analysis and network analysis, followed by modules selection. Most of
      the DEGs were involved in signaling pathways and in immune response. We
      identified three modules that were mostly impacted by ADA therapy and included
      genes involved in mitogen activated protein (MAP) kinase, wingless related
      integration site (Wnt), fibroblast growth factor (FGF) receptor, and Toll-like
      receptor (TCR) signaling. A separate analysis showed that a higher percentage of
      DEGs was modified by ADA in responders (44%) compared to non-responders (12%).
      Moreover, only in the responder group, TNF, Wnt, TLRs and type I interferon
      signaling were corrected by the treatment. We hypothesize that these pathways are
      strongly associated to AS pathogenesis and that they might be considered as
      possible targets of new drugs in the treatment of AS.

PMID- 28441779
TI  - Glyoxalase Goes Green: The Expanding Roles of Glyoxalase in Plants.
AB  - The ubiquitous glyoxalase enzymatic pathway is involved in the detoxification of
      methylglyoxal (MG), a cytotoxic byproduct of glycolysis. The glyoxalase system
      has been more extensively studied in animals versus plants. Plant glyoxalases
      have been primarily associated with stress responses and their overexpression is
      known to impart tolerance to various abiotic stresses. In plants, glyoxalases
      exist as multigene families, and new roles for glyoxalases in various
      developmental and signaling pathways have started to emerge. Glyoxalase-based MG
      detoxification has now been shown to be important for pollination responses.
      During self-incompatibility response in Brassicaceae, MG is required to target
      compatibility factors for proteasomal degradation, while accumulation of
      glyoxalase leads to MG detoxification and efficient pollination. In this review,
      we discuss the importance of glyoxalase systems and their emerging biological
      roles in plants.

PMID- 28441780
TI  - Pollen Grain Preservation and Fertility in Valuable Commercial Rose Cultivars.
AB  - In the cut flower market, traditional breeding is still the best way to achieve
      new rose cultivars. The geographical delocalization of cultivar constitution
      (generally made in Europe and North America) and plant cultivation (large areas
      in Africa and South America) represents a limit point for crossing and selection.
      Rose breeders often need to overcome geographical distances, resulting in
      asynchrony in flowering among crossing parents, by storing and sending pollen.
      Hence, a key aspect in breeding programs is linked to pollen availability and
      conservation, jointly with the identification of parameters related to pollen
      fertility. In this study we present the results of three different trials. In the
      first, pollen diameter and pollen viability were chosen as fertility predictors
      of 10 Rosa hybrida commercial cultivars. In the second trial, aliquots of dried
      pollen grains of six R. hybrida cultivar were stored under two different
      temperatures (freezer at T = -20  degrees C and deep freezer at T = -80  degrees
      C) and after a wide range of conservation period, their viability was measured.
      In the third trial, the effective fertilization capacity of frozen pollen of 19
      pollen donor cultivars was evaluated during 2015 crossing breeding plan,
      performing 44 hybridizations and correlating the number of seeds and the ratio
      seeds/crossing, obtained by each cultivar, with in vitro pollen germination
      ability.

PMID- 28441781
TI  - Dengue Virus Non-Structural Protein 5.
AB  - The World Health Organization estimates that the yearly number of dengue cases
      averages 390 million. This mosquito-borne virus disease is endemic in over 100
      countries and will probably continue spreading, given the observed trend in
      global warming. So far, there is no antiviral drug available against dengue, but
      a vaccine has been recently marketed. Dengue virus also serves as a prototype for
      the study of other pathogenic flaviviruses that are emerging, like West Nile
      virus and Zika virus. Upon viral entry into the host cell and fusion of the viral
      lipid membrane with the endosomal membrane, the viral RNA is released and
      expressed as a polyprotein, that is then matured into three structural and seven
      non-structural (NS) proteins. The envelope, membrane and capsid proteins form the
      viral particle while NS1-NS2A-NS2B-NS3-NS4A-NS4B and NS5 assemble inside a
      cellular replication complex, which is embedded in endoplasmic reticulum (ER)
      derived vesicles. In addition to their roles in RNA replication within the
      infected cell, NS proteins help the virus escape the host innate immunity and
      reshape the host-cell inner structure. This review focuses on recent progress in
      characterizing the structure and functions of NS5, a protein responsible for the
      replication and capping of viral RNA that represents a promising drug target.

PMID- 28441783
TI  - Comparison between MR Perfusion and 18F-FDG PET in Differentiating Tumor
      Recurrence from Nonneoplastic Contrast-enhancing Tissue
AB  - Objective: Comparison of the accuracy of MR perfusion and 18-FDG-PET for
      differentiating tumor progressionfrom nonneoplastic contrast-enhancing tissue.
      Methods and Materials: Retrospective review of MR perfusion and18-FDG-PET in 23
      cases of primary brain tumors (17 high grade and 6 low grade glial neoplasms) and
      5 cases ofmetastatic lesions with enhancing lesions on post-treatment MRI was
      performed. The accuracy of MR perfusion versus18-FDG-PET for distinguishing
      between nonneoplastic contrast-enhancing tissue and tumor recurrence was
      assessed.Results: Both CBV (p<0.004) and SUV (p<0.02) are higher in recurrent
      tumors than necrosis. MR perfusion has anaccuracy of 94.5% for differentiating
      between tumor recurrence and necrosis, while 18-FDG-PET has an accuracy of85.1%
      for differentiating between tumor recurrence and nonneoplastic contrast-enhancing
      tissue. Conclusion: Overall,recurrent tumor demonstrates significantly higher CBV
      and SUV than nonneoplastic contrast-enhancing tissue. However,MR perfusion
      appears to be more accurate than FDG PET for distinguishing the two entities.

PMID- 28441782
TI  - Deep Sequencing Analysis of RNAs from Citrus Plants Grown in a Citrus Sudden
      Death-Affected Area Reveals Diverse Known and Putative Novel Viruses.
AB  - Citrus sudden death (CSD) has caused the death of approximately four million
      orange trees in a very important citrus region in Brazil. Although its etiology
      is still not completely clear, symptoms and distribution of affected plants
      indicate a viral disease. In a search for viruses associated with CSD, we have
      performed a comparative high-throughput sequencing analysis of the transcriptome
      and small RNAs from CSD-symptomatic and -asymptomatic plants using the Illumina
      platform. The data revealed mixed infections that included Citrus tristeza virus
      (CTV) as the most predominant virus, followed by the Citrus sudden death
      associated virus (CSDaV), Citrus endogenous pararetrovirus (CitPRV) and two
      putative novel viruses tentatively named Citrus jingmen-like virus (CJLV), and
      Citrus virga-like virus (CVLV). The deep sequencing analyses were sensitive
      enough to differentiate two genotypes of both viruses previously associated with
      CSD-affected plants: CTV and CSDaV. Our data also showed a putative association
      of the CSD-symptomatic plants with a specific CSDaV genotype and a likely
      association with CitPRV as well, whereas the two putative novel viruses showed to
      be more associated with CSD-asymptomatic plants. This is the first high
      throughput sequencing-based study of the viral sequences present in CSD-affected
      citrus plants, and generated valuable information for further CSD studies.

PMID- 28441784
TI  - Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease
AB  - Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an
      inhibitory immunoregulatoryreceptor, has been recently implicated in tumor
      biology and tumor-associated immune suppression. In the present study,expression
      of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at
      both mRNA and proteinlevels. Methods: A total of 133 gastric tissue biopsies,
      comprising 43 from GC cases, 48 from PUD and 42 fromnon-ulcer dyspepsia (NUD)
      serving as controls were collected. Additionally, non-neoplastic adjacent tissue
      biopsieswere also obtained from 6 patients with GC. Infection with Helicobacter
      pylori was determined by the rapid urease testfor all participants and H&E
      staining was conducted for GC and PUD patients. Tim-3 relative mRNA expression
      wasdetermined by SYBR Green based Real-Time PCR using beta-actin as a reference
      gene. Tim-3 protein expression wasalso studied by immunohistochemistry in 7 GC, 7
      PUD and 10 NUD tissue samples. Results: Tim-3 was expressed athigher levels in GC
      (p=0.030) and PUD (p=0.022) cases compared to he NUD group. Among paired samples
      obtainedfrom gastric cancer patients, tumor tissues showed elevated Tim-3
      expression (p=0.019) in comparison with adjacentnon-neoplastic biopsies. Tim-3
      mRNA findings were supported by detection of more Tim-3 protein in
      cancerous(p=0.002) and ulcerative (p=0.01) tissues than in controls. Tim-3 was
      similarly expressed in H. pylori positive andnegative cases.Conclusion: Higher
      Tim-3 expression in patients with gastric cancer and peptic ulcer implies that
      itmight be involved in immune regulation and establishment of these
      gastrointestinal diseases. Targeted immunotherapyby blocking of inhibitory
      receptors like Tim-3 could be a promising approach for gastric cancer treatment.

PMID- 28441785
TI  - Evaluation of Cytotoxic and Genotoxic Effects of Euphorbia Triaculeata Forssk.
      Extract
AB  - Objective: To evaluate the cytotoxic and genotoxic activity of Euphorbia
      triaculeata Forssk. plant extract fromJazan region, Saudi Arabia, in an in vitro
      cancer model, which could be beneficial in anticancer therapy against humanbreast
      cancer cell line (MCF-7), prostate cell line (PC-3), human hepatocellular
      carcinoma cell line (HEPG2) and normalbreast epithelial cell line (MCF-10A). The
      human foreskin fibroblast cell line, (Hs68), was also included in the cellpanel.
      Doxorubicin and 5-Flurouracil, broad-spectrum anticancer drugs, were used as the
      positive control. Methods:Cytotoxicity of Euphorbia triaculeata plant extract was
      investigated by employing MTT assay and the genotoxicitywas assessed by using
      comet assay. Results: Both toxicity tests exhibited significant toxicity results.
      In the comet assay,the Euphorbia triaculeata extract exhibited genotoxic effects
      against MCF-7 DNA and PC 3 but not on HEPG2 celllines in a time-dependent manner
      by increasing the mean percentage of DNA damage. Euphorbia triaculeata
      extractshowed significant toxicity against cancer cells. Comparison with positive
      control signifies that cytotoxicity exhibitedby methanol extract might have
      moderate activity. Conclusion: The present work confirmed the cytotoxicity
      andgenotoxicity of Euphorbia triaculeata plant. However, the observed toxicity of
      this plant extract needs to be confirmedby additional studies. Based on our
      results, further examination of the potential anticancer properties of
      Euphorbiatriaculeata plant species and the identification of the active
      ingredients of these extracts is warranted.

PMID- 28441786
TI  - Application of Pineapple Juice in the Fish Digestion Process for Carcinogenic
      Liver Fluke Metacercaria Collection
AB  - Pepsin is common digestive enzyme used for fish digestion in the laboratory to
      collect trematode metacercariae.In a field study, to survey the infected fish is
      needed a huge yield of pepsin and it is very expensive. Therefore, ourpurpose of
      this study was to investigate the candidate enzyme from pineapple juice which has
      a digestive enzyme calledbromelain, a mixture of proteolytic enzymes, to digest
      fish in order to harvest metacercariae. Fish were divided into 2groups: one group
      in which metacercariae were harvested using acid pepsin as a control and other
      groups in which thefish was digested using fresh pineapple juices. The results
      showed that pineapple juice is able to digest fish similarly topepsin. The
      Pattavia pineapple juice had the highest number of metacercariae similar to the
      control. For Trat Si Thongpineapple juice,we found the number of metacercariae
      was less than control. This result suggests that the Pattaviapineapple juice was
      optimal juice for fish digestion to metacercaria collection and can be used
      instread of pepsin acid.

PMID- 28441787
TI  - Codon Usage Optimization and Construction of Plasmid Encoding Iranian Human
      Papillomavirus Type 16 E7 Oncogene for Lactococcus Lactis Subsp. Cremoris MG1363
AB  - HPV 16 intratypic sequence variations has been recognized in association with
      oncogenic potential diverge andgeographic distribution. This study aimed to
      investigate nucleotide modifications and optimization of HPV 16 E7regions from
      Iranian infected women. Cervical biopsies from 79/163 HPV 16 positive cancer
      patients detected inour study were analyzed by PCR in a couple of cloning of a
      complete ORF of the E7 gene, and sequencing. Themost frequently observed variant
      was C196T in E7 which led to an amino acid change of R66W. In addition, onlyone
      common variant T234G was identified from all specimens, but it did not lead to
      any amino acid change. We alsodetected nucleotide variations A86G, and C188T in
      samples. Among 99 codons in E7 gene, 56 codons were improvedfor Lactococcus
      lactis subsp. cremoris MG1363 resulting in a reduced G+C content from 43.1% to
      34.0%. Also, theAT%, ENC, and CAI values were 66, 20+/-1.1, and 1.000 instead of
      56.90, 60 +/-1.1, and 0.406 respectively. Finally weconstructed expression vector
      pNZ8148 encoding optimized E7 oncoprotein of HPV 16. This study declared for
      thefirst time, the genetic variations of HPV 16 E7 in IRAN. We conclude that
      plasmid pNZ8148-HPV 16-opti E7 can bepotential vaccine candidates in the future.

PMID- 28441788
TI  - Hsp27 and Hsp70 Expression in Esophageal Squamous
AB  - Twenty-eight specimens of Esophael squamous cell carcinoma (ESCC) were obtained
      by surgery procedures.Thetissues were fixed in formalin and embedded in paraffin.
      In each case, all available hematoxylin and eosin stainedsections were examined
      and a representative block was selected. The ages of these patients ranged from
      40 to 93years, with a mean age of 60 years. Results. The histological grade of
      tumors was 4 well-differentiated, 19 moderatelydifferentiated and 5 poorly
      differentiated. Expression of Hsp27 and Hsp70 in ESCC was demonstrated in 23
      (82,14%)and 26 (92,86%) cases, respectively. Adjacent normal mucosa was positive
      in 11 (39,29%) samples and 9 (32,15%)samples for Hsp27 and Hsp70, respectively.
      No relationship between the expression of Hsp27 and Hsp70 with
      theclinicopathological parameters, including gender, age, surgical margin, lymph
      node status and tumor differentiation.The median follow-up period was 60 months.
      Survival analysis of patients with ESCC showed no relationship withthe expression
      of Hsp27 and Hsp70. Conclusion. Taken together, our results demonstrate that
      Hsp27 and Hsp70 areexpressed in ESCC tissues, but they are not good prognostic
      factor for patients with ESCC.

PMID- 28441789
TI  - Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and
      Doxorubicin on MCF7 and MDA-MB-231 Cell Lines
AB  - Objective: Breast cancer is a heterogeneous disease and very common malignancy in
      women worldwide. The efficacyof chemotherapy as an important part of breast
      cancer treatment is limited due to its side effects. While
      pharmaceuticalcompanies are looking for better chemicals, research on traditional
      medicines that generally have fewer side effects isquite interesting. In this
      study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was
      compared in MCF7,and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA
      MB-231 cells were cultured in RPMI 1640containing 10% FBS and 100 U/ml
      penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI)
      kitwere used respectively to compare the survival rate and apoptotic effects of
      different concentrations of doxorubicin andArctium lappa root extract on MDA-MB
      231 and MCF7 cells. Results: Arctium lappa root extract was able to reducecell
      viability of the two cell lines in a dose and time dependent manner similar to
      doxorubicin. Flow cytometry resultsshowed that similar to doxorubicin, Arctium
      Lappa root extract had a dose and time dependent apoptosis effect onboth cell
      lines. 10MUg/mL of Arctium lappa root extract and 5 MUM of doxorubicin showed the
      highest anti-proliferativeand apoptosis effect in MCF7 and MDA231 cells.
      Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+)cell lines represent two
      major breast cancer subtypes. The similar anti-proliferative and apoptotic
      effects of Arctiumlappa root extract and doxorubicin (which is a conventional
      chemotherapy drug) on two different breast cancer celllines strongly suggests its
      anticancer effects and further studies.

PMID- 28441790
TI  - Eradicating Breast Cancer: Longevity Impact on Kuwaiti Women
AB  - Objective: To explore salient trends in incidence and mortality from breast
      cancer among Kuwaiti females and toquantify the number of years that could be
      saved if breast cancer deaths were eliminated. Methods: Appling life
      tabletechnique, the paper constructs a bridged, multiple decrement and cancer
      elimination life tables for Kuwaiti females.Data sources include Kuwait Cancer
      Control Center Registry along with vital statistics on mortality by age
      groups,nationality, and causes of death according to ICD-10 revision. Result: The
      study finds that, without interventions,nearly 2.5% of Kuwaiti female live births
      are expected to die from breast cancer. By contrast, if this disease were tobe
      completely eradicated, Kuwaiti females are expected to gain half a year of life
      expectancy at birth. Likewise, a10% reduction in deaths attributed to breast
      cancer would produce a gain of 11 days of life at age 30. The gain wouldaugment
      to 51 days when death is reduced by 50%. Kuwaiti females aged 50 would add almost
      5 months when breastcancer is eradicated, while a 20 percent reduction in breast
      cancer mortality would raise their life expectancy by 26 days.Conclusion: The
      results strongly support policy interventions of Kuwait's government by
      instituting a well-documentedpublic health policy for chronic diseases and
      mitigating the increase of cancer prevalence.

PMID- 28441791
TI  - Selective Toxicity of Non Polar Bioactive Compounds of Persian Gulf Sea Squirt
      Phallusia Nigra on Skin Mitochondria Isolated from Rat Model of Melanoma
AB  - Background: Skin cancer is the most prevalent cancer and one of the major causes
      of mortality worldwide. Marinanimals have attracted much attention in recent
      years as useful substances having application in medicine. It was shownthat
      Phallusia nigra (P. nigra) known as sea squirt could play an important role in
      cancer therapy. Methods: This studywas designed to figure out the probable
      selective toxicity of n-hexane, diethyl ether, methanolic and aqueous extractsof
      P. nigra on cancerous mitochondria isolated from the skin of melanoma induced
      rats. In our study, mitochondriawere isolated from the skin tissue of both
      melanoma induced and normal healthyrats. Different concentrations of
      fourdifferent extracts of P. nigra (250, 500 and 1000 MUg/ml) were added to
      mitochondrial samples obtained from both groups,separately. Results: Our results
      showed that n-hexane, diethyl ether and methanolic extracts (but not aqueous
      extract)of P. nigra in all concentrations applied (250, 500 and 1000 MUg/ml)
      significantly induced toxic alterations only in thecancerous but not normal
      healthy skin mitochondria including; increased reactive oxygen species (ROS)
      formation,mitochondrial swelling, decreased mitochondrial membrane potential
      (MMP) and cytochrome c release. Flow-cytometryanalysis demonstrated that n
      hexane, diethyl ether and methanolic extracts of P. nigra progressively induced
      apoptosisand necrosis only on melanoma cells but not healthy skin cells.
      Conclusions: Our results suggest that non polar bioactivecompounds in P. nigra
      may be hopeful candidates for further studies including molecular identification,
      confirmatoryin vivo experiments and finally clinical trials designed for new drug
      treatment of melanoma skin cancer.

PMID- 28441792
TI  - Urinary Iodine Concentrations in Cancer Patients
AB  - Background: It has been suggested that incidence of some cancers, especially
      examples in the breast and stomachmay be influenced by the iodine intake.
      However, only few studies are available at present. Therefore, we have
      conductedthe present assessment of iodine status in Iranian patients diagnosed
      with a malignancy. Materials and Methods:This cross-sectional study was conducted
      in 85 patients diagnosed with different types of cancer at Shahid
      SadoughiHospital, Yazd, Iran. The method used was based on the Sandell-Kolthoff
      reaction. Results: The median urinary iodineconcentration (UIC) was 17.4 MUg/L,
      with <=20 MUg/L indicative of severe iodine deficiency. According to the WHO/IC
      CIDD/UNIC EF classification, 88.1%, 7.1% and 2.4% of patients had a UIC <20
      (severe), 20-49 (mild), and 50-99 MUg/L(moderate), respectively. There was no
      statistically significant differences in UIC between men and women.
      Conclusion:The UIC values indicate that Iranian cancer patients were seriously
      iodine deficient according to WHO/UNIC EF/IC C IDD, and that this is a suitable
      index to assess iodine status in Iranians. Daily consumption of salt fortified
      withiodine or other approaches to increase intake might be effective strategies
      for prevention or reduction of malignancies.

PMID- 28441793
TI  - Patterns, Beliefs, Norms and Perceived Harms of Hookah Smoking in North Iran
AB  - Introduction: Hookah smoking is considered as a public health threat around the
      globe. The aim of this study wasto investigatethe hookah smoking patterns,
      beliefs, norms and perceived harms in Golestan province of Iran. Methods:A cross
      sectional study was conducted on 395 hookah smokers using convenience sampling
      method in 2015. To collectdata, Heinz's hookah patternwas utilized. Ordinal
      regression models were used to exploring of covariates related to theodds of life
      time, last-30-day, and current hookah use. Results: In general, 357 (90.4%)
      subjects were male smokers.Most of subjects smoked hookah in cafe (62.2%) and
      with friends (75.6%). The majority of them (71.1%) did notconsider themselves as
      a hooked person. Cigarette smoking (OR =.65, 95 % CI .42-.98), low perceived
      addictivenessof hookah than cigarettes (OR =2.33, 95 % CI 1.45-3.73), Social
      context of hookah smoking with friends in cafe(OR =1.14, 95 % CI 1.08-1.2), and
      number of close friends who smoked hookah (OR =1.38, 95 % CI 1.18-1.61)
      wereeffective variables affected the past month use of hookah.
      Conclusion:Development, implementation and assessmentof interventions
      particularly adapted to hookah smoking regarding increase of perceived harm of
      hookah than cigaretteand its probable addiction focusing on close friends
      appeared to be beneficial.

PMID- 28441794
TI  - Reciprocal Interactions of Leukemic Cells with Bone Marrow Stromal Cells Promote
      Enrichment of Leukemic Stem Cell Compartments in Response to Curcumin and
      Daunorubicin
AB  - A predominant challenge in developing curative leukemia therapy is interactions
      of leukemic cells with the bonemarrow stromal microenvironment. We aimed to
      investigate the role of stromal cells, such as bone marrow mesenchymalstromal
      cells (BMSCs) and osteoblasts (OBs), in curcumin (CUR) and daunorubicin (DNR)
      induced apoptosis of acutemyeloid leukemia (AML) cells. We used KG1 and U937 as
      leukemia cell line models and treated them with CUR andDNR. The cells were then
      co-cultured with BMSCs or a combination of BMSCs and OBs as feeders. After 24
      hoursof co-culture, BMSCs or OBs were sorted and separated from the leukemia
      cells and apoptosis levels were analyzedby annexin/propidium iodide (PI) staining
      on flow cytometry. Potentially involved molecular pathways were analyzedat gene
      and protein levels by Real time PCR and western blotting, respectively. The
      results showed AML cells coculturedwith BMSCs plus OBs to be more resistant to
      drug induced-apoptosis compared to co-culture with BMSCsalone or without co
      culture. Expression levels of OPN, CXCL-12, IL-6, STAT-3 and VCAM-1 were also
      significantlyup-regulated in OBs and AML cells, at both mRNA and protein levels
      after co-culture, with concurrent enrichment ofCD34+ AML cells. Our data showed,
      in a stromal cell niche-based model, that OBs revoke the influence of BMSCson
      leukemic cells and promote enrichment of both CD34+ and CD34- leukemic stem cell
      (LSC) compartments inresponse to CUR and DNR. Up-regulation of OPN, CXCL-12, IL
      6, STAT-3 and VCAM-1 in OBs and AML cellsin co-culture might be part of molecular
      mechanisms that block CUR or CUR+DNR-induced apoptosis and promoteenrichment of
      CD34+ and CD34- LSCs.

PMID- 28441795
TI  - YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via
      Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages.
AB  - Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are
      known to possess anti-oxidative and anti-inflammatory properties. In the present
      study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3
      (2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its
      inhibitory effects on endotoxin-stimulated production of reactive oxygen species
      (ROS) and expression of inflammatory mediators in macrophages. We demonstrated
      that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed
      lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7
      substantially decreased NADPH oxidase activity stimulated by LPS, indicating that
      YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages.
      Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory
      mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti
      inflammatory properties, as well as anti-oxidative activity. In continuing
      experiments to investigate the mechanisms that could underlie such biological
      effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK
      stimulated by LPS, whereas no significant effect on ERK was observed.
      Furthermore, LPS-stimulated production of ROS, activation of NADPH oxidase and
      expression of inflammatory mediators were markedly suppressed by treatment with
      selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together,
      these results demonstrated that YJI-7, a novel synthetic chalcone derivative,
      suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and
      diminished expression of inflammatory mediators, at least in part, via down
      regulation of p38MAPK and JNK signaling in macrophages.

PMID- 28441796
TI  - Role of Dietary Crocin in In Vivo Melanoma Tumor Remission
AB  - Background: Melanoma is a deadly form of malignancy. Early diagnosis might pave
      the way to cure but its aggressivenature leads to rapid dissemination and
      colonization of distant organs. Dietary herbs may play a significant role
      inprevention of cancer. In this study, we tested anti-tumor efficacy of the
      Crocus sativus derived active constituent crocin,it is well established to have
      anti-cancer properties in different cancer models by our group and other groups.
      Notably,crocin is reported to exert anti-proliferative effect on melanoma cells
      (B16F10) in vitro. However, roles of crocin onin vivo melanoma tumor remission
      have not yet been reported to our knowledge. Materials and Methods: Melanomatumor
      model was established by transplanting B16F10 (5 X 105) cells into C57BL/6 mice,
      which were then observedfor tumor development and once the tumor volume reached 6
      mm, mice were divided into (Group I: tumor-bearinganimals treated with normal
      saline and Group II: counterparts treated with crocin at 2 mg/kg body weight for
      21 days).. Tumor remission and tumor growth related parameters such as tumor
      silent period (TSP), tumor volume doubling time(VDT), growth delay (GD), and mean
      survival time (MST) were determined. In addition, serum protein profiles
      wereanalyzed. Results: The 21 days crocin treatment significantly reduced the
      tumor burden in mice, extending the meansurvival time significantly as compared
      to control. Crocin treatment also significantly increased the TGD and TSP
      anddecreased VDT. Furthermore, while serum proteins such as albumin and globulin
      (alpha1, alpha2, beta, and gamma)were altered due to tumor burden, crocin
      treatment resulted in their levels near to normal at the end of the
      experimentalperiod. Conclusion: Our study provided clear evidence that crocin may
      exhibit significant melanoma tumor remissionproperties by positively modulating
      tumor growth related parameters. In future, the molecular mechanisms of
      crocinaction should be studied extensively in melanoma models before defining
      crocin-based melanoma drug formulations.

PMID- 28441797
TI  - Breast Cancer Awareness among Women in Western Amazon: a Population Based Cross
      Sectional Study
AB  - Background: A general lack of women's awareness of breast cancer has been one of
      the barriers to screeningand early presentation. Thus, the aim of this study was
      to evaluate levels of knowledge about risk factors, and earlywarning signs of
      breast cancer, and to determine factors associated with better levels of
      comprehension. Methods: Apopulation-based cross-sectional study was carried out
      among 478 women over 40 years old, living in Rio Branco city,western Amazon. All
      were interviewed using the "Breast cancer knowledge, attitudes and practice
      scale", developedby American Cancer Society. Results: Among the respondents, only
      28.6% of women were aware that advanced agehighly increases the risk. Around 30%
      of participants recognized nipple retraction as a sign of breast cancer.
      Breastcancer knowledge varied according to age in such a way that the mean scores
      were high from 40-69 years and decreaseddramatically among those aged >=70 (beta=
      0.06,p=0.031). Access to health services such as the Pap-test
      (beta=2.45,p=0.027)and attending a gynecologist in the past two years
      (beta=1.88,p=0.005) were statistically associated with the score ofbreast cancer
      knowledge. Conclusion: The findings indicate that women living in urban areas,
      having gynecologicalassessment, considering herself at high risk of developing
      breast cancer and thinking that breast cancer is a fatal diseaseare statistically
      associated with good knowledge of breast cancer risk factors, signs and symptoms,
      even adjusting forage and education.

PMID- 28441798
TI  - [The current problems and management strategy of standardized surgical treatment
      of differentiated thyroid carcinoma in China].

PMID- 28441799
TI  - [Treatment of bilateral vocal cord paralysis by hemi-phrenic nerve transfer].
AB  - Objective: To investigate the surgical effect of reinnervation of bilateral
      posterior cricoarytenoid muscles(PCA) with left hemi-phrenic nerve and endoscopic
      laser arytenoid resection in bilateral vocal cord fold paralysis(BVFP) and to
      analyze the pros and cons of the two methods. Methods: One hundred and seventeen
      BVFP patients who underwent reinnervation of bilateral PCA using the left hemi
      phrenic nerve approach (nerve group, n=52) or laser arytenoidectomy(laser group,
      n=65) were enrolled in this study from Jan.2009 to Dec.2015.Vocal perception
      evaluation, video stroboscopy, pulmonary function test and laryngeal
      electromyography were preformed in all patients both preoperatively and
      postoperative1y.Extubution rate was calculated postoperative1y. Results: Most of
      the vocal function parameters in nerve group were improved postoperatively
      compared with preoperative parameters, albeit without a significant
      difference(P>0.05), while laser group showed a significant deterioration in voice
      quality postoperative1y(P<0.05). The two groups showed significant difference in
      voice quality postoperative1y(P<0.05). Videostroboscopy showed that vocal fold on
      the operated side in both groups could abduct to various extent postoperatively,
      which showed significant difference when compared with preoperative abductive
      movements (P<0.05). But the amplitude in nerve group was larger than that in
      laser group (P<0.05). 89% of the patients in nerve group were inhale
      physiological vocal cord abductions. Postoperative glottal closure showed no
      significant difference in nerve group (P>0.05), while showed various increment in
      laser group(P<0.05). Differences between the two groups were statistically
      significant(P<0.05). The pulmonary function in both groups was better after
      operation, reaching the reference value. Postoperative laryngeal electromyography
      confirmed successful reinnervation of the bilateral PCA muscles. The
      decannulation rate were 88.5% and 81.5% in nerve group and laser group
      respectively. In both groups, patients presented aspiration symptoms
      postoperatively, and rdieved soon, except 2 patients in laser group suffered
      repeated aspiration. Conclusions: Reinnervation of bilateral PCA muscles using
      left hemi-phrenic nerve can restore inspiratory vocal fold abduction to a
      satisfactory extent while preserving phonatory function at the preoperative level
      without evident morbidity, and do not affect swallowing function, greatly
      improving the quality of life of the patients.

PMID- 28441800
TI  - [Risk for metastasis of lymph node between sternocleidomastoid and sternohyoid
      muscle in papillary thyroid cancer].
AB  - Objective: To analyze the risk factors for metastasis of lymph nodes between
      sternocleidomastoid and sternohyoid muscle (LNSS) in papillary thyroid cancer
      (PTC). Methods: Papillary thyroid cancer patients with clinically positive
      lateral lymph node metastasis (cN1) who underwent surgery including LNSS
      dissection between May 1, 2013 and May 31, 2016 at the Department of Head and
      Neck Surgery, Fudan University Shanghai Cancer Center were retrospectively
      studied. Logistic regression analysis was performed to evaluate possible
      clinicopathological factors related to LNSS metastasis. Results: In 85 patients,
      54 patients (63.5%) showed LNSS in their surgical specimen, and 20 patients
      (23.5%) had pathologically positive LNSS metastasis. Patients with LNSS showed
      preoperatively higher levels of serum thyroid stimulating hormone (TSH) and
      thyroid peroxidase antibody (TPO-Ab) compared to patients only with fibrofatty
      tissues between sternocleidomastoid and sternohyoid muscle (P<0.05), and they
      also displayed a higher proportion of multifocality in ipsilateral thyroid lobe
      (P<0.05). Multi-factor analysis indicated that LNSS metastasis was correlated
      with original tumor size (OR=1.819, 95%CI 1.050-3.850, P=0.002) and Level IV
      lymph node metastasis (OR=2.190, 95%CI 1.132-2.334, P=0.005). Furthermore, the
      number of positive LNSS was tightly correlated to that of level IV lymph node
      metastasis(P<0.05). Conclusion: LNSS metastasis is occult but not quite rare in
      PTC. Patients with extensive lymph node metastasis in Level IVhave a higher risk
      for metastasis of LNSS.

PMID- 28441801
TI  - [Prediction of occult carcinoma in contralateral nodules based on the ultrasonic
      features of unilateral papillary thyroid carcinoma].
AB  - Objective: To investigate the occurrence of occult carcinoma in contralateral
      lobes based on the ultrasonic features of unilateral papillary thyroid carcinoma.
      Methods: The study included 202 consecutives cases of unilateral papillary
      thyroid carcinoma with benign nodules in the contralateral lobe identified by
      preoperative ultrasound or fine-needle aspiration from June 2014 to December
      2015. All patients received total thyroidectomies, and with postoperative
      pathological examination they were divided into two groups, one including 60
      cases with positive occult cancer and another one consisting of 142 cases with
      negative occult cancer. Univariate and multivariate analyses were performed to
      analyze the sonographic features of unilateral papillary thyroid carcinoma
      relevant to the occurrence of occult carcinoma in the contralateral nodules.
      Results: Univariate analysis indicated occult carcinoma in the contralateral
      lobes was associated with Hashimoto's thyroiditis(chi(2)=3.955, P=0.047), unclear
      border (chi(2)=4.375, P=0.036)and multifocality in the ipsilateral(chi(2)=7.375,
      P=0.007), but not with tumors maximum size, location, A/T, shape, internal
      structure, internal echo, acoustic halo, calcification, capsular invasion and
      blood flow signal in the lobe with carcinoma on another side. Multivariate
      analysis showed unclear border (OR=2.727, P=0.010) and multifocality in the
      ipsilateral(OR=2.807, P=0.005)of carcinoma were independent predictive factor for
      contralateral occult PTC. Conclusions: Unclear border and multifocality of PTC in
      the ipsilateral were closely relevant to the occurrence of occult carcinoma in
      the contralateral nodules.

PMID- 28441802
TI  - [Central compartment reoperation for recurrent/persistent differentiated thyroid
      cancer].
AB  - Objective: To analyze the incidences of complications after central compartment
      reoperation for recurrent/persistent differentiated thyroid cancer, and to
      investigate the safety and feasiblity of central compartment reoperation.
      Methord: A total of 109 patients who underwent central compartment reoperation
      for recurrent/persistent differentiated thyroid cancer from January 1, 2011 to
      March 31, 2016 in Cancer Hospital, Chinese Academy of Medical Sciences was
      analysed retrospectively, and the incidences of reoperation-related complications
      were evaluated. Results: Among 109 patients, only 10 (9.2%) patients were treated
      initially in our hospital and remaining patients (90.8%) treated initially in the
      other hospitals. Surgical approaches for thyroid beds: 61 patients (56.0%)
      underwent supplemented total thyroidectomy, 3 patients (2.8%) for removal of
      recurrent thyroid cancer, 2 patients (1.8%) with supplemented total thyroidectomy
      and removal of recurrent thyroid cancer, and 12 cases (11.0%) had bilateral
      thyroid lobectomy. Central compartment lymph node dissection: 66 patients (60.6%)
      underwent bilateral central neck dissection, 40 patients (36.7%) with unilateral
      central neck dissection. A total of 16 patients (14.7%) had complications.
      Transient and permanent vocal fold paralysis developed in 9(8.3%) and 2(1.8 %)
      patients, respectively. Transient and permanent hypoparathyroidism occurred in
      2(1.8%) patients and 11 patients (10.1%), respectively. Postoperative bleeding
      happened in 1 patient (0.9%). with follow-up from 7 to 61 month, median follow-up
      was 17.2 months. All patients survived, with recurrence in 3 (2.8%) patients.
      Conclusions: It seems the incidences of complications for thyroid carcinoma
      reoperation in central compartment is low for the experienced surgeon. The
      reoperation was safe and feasible.

PMID- 28441803
TI  - [Factors for lymph node metastasis and survival rate in papillary thyroid
      microcarcinoma: from a large cohort of 3 607 cases series].
AB  - Objective: To investigate high-risk factors for lymph node metastasis (LNM) and
      10-year survival rate in patients with papillary thyroid microcarcinoma (PTMC).
      Methods: We retrospectively analyzed the clinical data of 3 607 patients with
      PTMC received surgery in our hospital from January 2005 to December 2015.
      Univariate and multivariate analyses were performed to identify the factors
      associated with metastasis and 10-year survival rate of the patients was
      calculated. Results: The patients accepted an average follow-up of 68 months,
      with follow-up from 18 to 138 months. Total LNM rate in the 3 607 patients with
      PTMC was 17.13%. Central lymph node metastasis rate was 16.86%, which was related
      to gender (males 21.89% vs females 15.26%, P<0.01), age (<45 years old 24.44% vs
      >=45 years old 11.96%, P<0.01), tumor diameter (P<0.01) and multifocality
      (P<0.01). Lateral lymph node metastasis rate was 1.05%, which was related to age
      (<45 vs >=45, P<0.01) and tumor diameter (P<0.01). The 10-year-survival rate was
      93.0% and 10-year recurrence-free survival rate was 87.5%. Conclusion: PTMC may
      metastasize to cervical lymph node, especially in males, with age younger than
      45, multifocal tumors and maximal tumor diameter larger than 0.7 cm. There was no
      significant correlation between these clinical features associated with LNM and
      the 10-year survival rate.

PMID- 28441804
TI  - [Olfactory bulb volume in patients with posttraumatic olfactory dysfunction].
AB  - Objective: To analyze the correlation between olfactory bulb(OB) volume and
      olfactory function in patients with posttraumatic olfactory dysfunction. Methods:
      Forty patients with posttraumatic olfactory dysfunction were compared with forty
      controls in terms of olfactory function T&T testing, OB volume assessed with
      magnetic resonance imaging (MRI). SPSS 17.0 software was used to analyze the
      data. Results: T&T olfactory testing revealed that patients with posttraumatic
      olfactory dysfunction had higher scores than controls(3.47+/-0.63 vs.1.39+/-0.19,
      t=4.317, P<0.05). Both men and women with posttraumatic olfactory dysfunction
      were affected by the same extent of olfactory loss(3.52+/-0.66 vs.3.43+/-0.61,
      t=0.896, P>0.05). Both men and women as controls were affected by the same extent
      of olfactory loss(1.41+/-0.20 vs.1.38+/-0.17, t=1.073, P>0.05). OB volume of left
      side in patients with posttraumatic olfactory dysfunction were (36.15+/
      3.16)mm(3,) right side were (39.28+/-3.76)mm(3,) average OB volume were (37.55+/
      3.42)mm(3;) OB volume of left side in controls were (81.74+/-5.87)mm(3,) right
      side were (83.58+/-6.13)mm(3,) average OB volume were (82.59+/-5.99)mm(3;) OB
      volumes were lower in patients with posttraumatic olfactory dysfunction as
      compared with controls(t value were 4.815, 4.837 and 4.825, all P<0.01). Average
      olfactory discriminate threshold was negatively correlated with average OB volume
      in posttraumatic olfactory dysfunction and controls(r value was-0.582, -0.564,
      both P<0.05). Average olfactory discriminate threshold was positively correlated
      with impairment degree in patients with posttraumatic olfactory dysfunction(r
      value was 0.472, P<0.05), average OB volume was negatively correlated with
      impairment degree in patients with posttraumatic olfactory dysfunction(r value
      was -0.397, P<0.05) Conclusions: The OB volumes are lower in patients with
      posttraumatic olfactory dysfunction as compared with controls. The OB volume is
      correlated with olfactory function. Impairment degree in patients with
      posttraumatic olfactory dysfunction is accordance with olfactory function
      lowering degree. Megnetic resonance imaging can be used as a supplementary
      diagnostic tool for patients with posttraumatic olfactory dysfunction.

PMID- 28441805
TI  - [Free medial thigh chimeric myocutaneous perforator flap for the reconstruction
      of tongue defect after tongue carcinoma resection].
AB  - Objective: To investigate the application of free medial thigh chimeric
      myocutaneous perforator flap in the reconstruction of tongue defect after radical
      resection of tongue carcinoma. Methods: From June 2013 to November 2015, 17 cases
      with tongue carcinoma underwent radical resection and tongue and mouth floor
      defects after surgery were reconstructed with medial thigh chimeric myocutaneous
      perforator flaps at the same stage. These 17 cases included tongue carcinoma on
      lingual margin (n=9), ventral tongue (n=7) and mouth floor (n=1). Appearance and
      functional results were evaluated with follow-up. Results: Medial thigh chimeric
      myocutaneous perforator flap was (9.0+/-0.3) cm in length, (4.5+/-0.3) cm in
      width , and (1.8+/-0.4) cm in thickness. The length of pedicle was (7.4+/-0.6)
      cm. All of the 17 flaps survived uneventfully, and the donor sites were closed
      directly in all cases. All patients were followed up for 10-28 months with
      satisfied esthetic and functional results in reconstructed tongue. Aside from
      linear scar in the donor sites, the functions of thighs were not affected. No
      local recurrence occurred. Conclusion: The free medial thigh chimeric
      myocutaneous perforator flap is an ideal choice to reconstruct the tongue and
      mouth floor defect after radical resection of tongue carcinoma.

PMID- 28441806
TI  - [Possible reasons for cerebrospinal fluid gusher in cochlear implantation with
      inner ear abnormality].
AB  - Objective: To discuss the possible reasons for cerebrospinal fluid (CSF) gusher
      in cochlear implantation (CI) with inner ear abnormality. Method: A retrospective
      analysis was performed on 340 cases who underwent CI from January 2013 to
      December 2016 in Division of Otology, Otorhinolaryngology Hospital, the First
      Affiliated Hospital of Zhengzhou University. Among them, 96 cases had inner ear
      abnormalities. Imaging examinations were performed on these patients, and
      classification of inner ear malformation was done according to the results.
      Results: Among the cases with inner ear abnormality, 9.4% (9/96) suffered from
      CSF gusher during CI. The inner ear abnormalities were found to be as follows: 3
      cases had incomplete partition type I; 1 case had incomplete partition type I
      with semicircular canal dysplasia; 1 case had common cavity deformity; 1 case had
      enlarged vestibular aqueducts and common cavity deformity; 2 cases had Mondini
      deformity. All of these cases had bony defect in the fundus of the internal
      acoustic meatus observed on CT scans. Another case was type 1 cochlear aqueduct
      with round window aplasia. Conclusions: Defects in the modiolus or fundus of the
      internal acoustic meatus is the main reason for CSF gusher during CI. A patent
      cochlear aqueduct is another possible reason.

PMID- 28441807
TI  - [The change of female progesterone level and blood calcium concentration in
      perimenopausal women with benign paroxysmal positional vertigo].
AB  - Objective: The estrogen level and blood calcium concentration changes were
      studied on menopausal women with benign paroxysmal positional vertigo (BPPV).
      Methods: Between January 2015 and January 2016, 70 menopause women with BPPV in
      outpatient clinics of Department of Otorhinolaryngology, Inner Mongolia Medical
      University Affiliated Hospital were included in this study as research group,
      while 30 menopause healthy women who came to hospital for check-up were included
      as control group. Serum levels of estradiol (E2), follicle stimulating hormone
      (FSH), luteinizing hormone (LH), progesterone (PRO), testosterone (T), serum
      prolactin (PRL) and the calcium concentration were analysed and comparied between
      research group and control group. SPSS17.0 statistical software was used to
      analyze the data. chi(2) test was used to compare the percentage of decreased
      serum level of sex hormone, and t test was used to compare the serum level of sex
      hormone and calcium concentration of two groups. Results: In research group, sex
      hormone decreased proportion of E2 (91%) and PRO (67%) were obviously higher than
      those in control group (chi(2) value was 8.13, 10.28, respectively, all P<0.05).
      The E2 and PRO in research group were significantly lower than those in control
      group ((33.18+/-31.45) pmol/L vs (64.92 +/-31.52) pmol/L, (0.64+/-0.48) nmol/L vs
      (1.02+/-0.60) nmol/L, t value was 6.238, 8.566, respectively, all P<0.05). There
      was no statistically significant difference of the level of LH, PRL, T, FSH and
      blood calcium concentration in research group compared with control group
      ((29.81+/-13.13) U/L vs (27.21+/-10.19) U/L, (0.49+/-0.20) nmol/L vs (0.49+/
      0.15) nmol/L, (0.56+/-0.42) nmol/L vs (0.73+/-0.62) nmol/L, (64.25+/-31.44) U/L
      vs (60.38+/-29.97) U/L, (2.28+/-0.17) mmol/L vs (2.32+/-0.21) mmol/L, t value was
      13.427, 14.876, 7.505, 12.090, 7.532, respectively, all P>0.05). Conclusion: The
      level of E2 and PRO decrease obviously in postmenopausal women with BPPV, which
      can cause the inner ear microcirculation disorder , may be one of the risk
      factors of BPPV.

PMID- 28441808
TI  - [Hypophosphatemia during the vestibular function examination and treatment in 7
      patients with vertigo].

PMID- 28441809
TI  - [Esophageal foreign body combined with internal jugular vein thrombosis: a case
      report].

PMID- 28441810
TI  - [Sudden deafness and vertigo as starting symptoms of relapsing polychondritis:
      one case report].

PMID- 28441811
TI  - [Reconstruction processing of multi-slice spiral CT in the diagnosis of complex
      bilateral inner ear malformation with cerebrospinal fluid otorrhea: one case
      report].

PMID- 28441812
TI  - [Sinonasal myxofibrosarcoma: a case report].

PMID- 28441813
TI  - [The special characteristics of differentiated thyroid carcinoma and the
      controversies in the surgical treatment on the patients with it].

PMID- 28441814
TI  - [Current situation and thinking of diagnosis and treatment in some types of
      thyroid cancer].
AB  - As arising incidence of thyroid cancer, the treatment for thyroid carcinoma is
      becoming increasingly standardized. But there are different opinions on the
      treatment for some types of thyroid cancers, including the determination of
      operative opportunity, surgical method, and follow-up observation plan. There are
      mainly two categories of patients, namely the patients diagnosed as familial
      thyroid cancer mutation carriers through family screening, including medullary
      thyroid carcinoma and familial nonmedullary thyroid carcinoma, and the patients
      with thyroid microcarcinoma that can be observed after diagnosed by fine needle
      biopsy cytology. We will discuss current situation for the diagnosis and
      treatment of these patients.

PMID- 28441815
TI  - [The interpretation of 2015 American Thyroid Association management guidelines
      for adult patients with thyroid nodules and differentiated thyroid cancer].
AB  - The prevalence of thyroid nodules, especially differentiated thyroid cancer, has
      increased during the past decades. With the consideration of increasing
      prevalence of the diseases, American Thyroid Association (ATA) updated the
      guidelines for adult patients with thyroid nodules and differentiated thyroid
      carcinoma (DTC) in 2015. The aim of the new guidelines was to minimize potential
      harm from overtreatment in majority of patients at low risk for diseasespecific
      mortality and morbidity while appropriately treat and monitor those patients at
      higher risk. The updates of contents in new ATA guidelines are interpreted in
      this article, including the contents about screening, diagnosis and treatment
      plan of nodules, initial surgical treatment of DTC, the evaluation and treatment
      of DTC after surgery, follow-up and diagnosis and treatment of recurrence,
      persistence, and distant metastasis of DTC.

PMID- 28441816
TI  - [Cartilage tympanoplasty].

PMID- 28441817
TI  - [Importance of neonatal screening for congenital heart disease in China].

PMID- 28441818
TI  - [To further deepen the understanding of radiofrequency a blation in the treatment
      of pediatric arrhythmia].

PMID- 28441819
TI  - [Consensus on antimicrobial management and infection prevention in primary
      immunodeficiency diseases].

PMID- 28441820
TI  - [Brief interpretation of "the Pediatric and Congenital Electrophysiology Society
      (PACES)and the Heart Rhythm Society (HRS) expert consensus statement on the use
      of catheter ablation in children and patients with congenital heart disease].

PMID- 28441821
TI  - [Assessment of undiagnosed critical congenital heart disease before discharge
      from the maternity hospital].
AB  - Objective: Undiagnosed critical congenital heart disease (CCHD) was assessed
      before discharge from maternity hospital.Basic information was provided for
      screening CCHD in the early neonatal stage.Chi-squared test was used for
      comparison of categorical variables(detection rate of different types of CCHD).
      Method: A retrospective cohort study was conducted in neonates with CCHD who were
      admitted to Children's Hospital of Fudan University between 1 January 2012 and 31
      December 2015. For comparing with the previously reported undiagnosed rate of
      CCHD at discharge, CCHD was defined as all duct dependent congenital heart
      disease (DDCHD) and any cyanotic CHD that required early surgery. Result: A total
      of 1 036 infants with CCHD were included. The prenatal detection rate of CCHD was
      14.04%(122/869). As a whole, 52.51% (544/1 036) of CCHD cases were undiagnosed at
      discharge, and 14.09%(146/1 036)were still missed after 6-week examination. The
      diagnoses most likely to be unrecognized at discharge included critical
      coarctation of the aorta (COA) (75.00%), total anomalous pulmonary venous
      connection (61.54%), pulmonary atresia (PA) with ventricle septal defect (VSD)
      (61.45%), single ventricle (SV) (60.10%) and critical aortic stenosis (52.94%).
      Among newborns diagnosed prior to discharge, 54.88% (270/492) due to symptom or
      prenatal ultrasonographic diagnosis, 45.12% (222/492) due to abnormal findings in
      routine examination. Among asymptomatic CCHD cases without prenatal diagnosis,
      71.02% (544/766) were undiagnosed and the most common delayed diagnosis was SV
      (82.78%), interrupted aortic arch (81.82%), transposition of the great arteries
      with intact ventricular septum (79.63%), PA/VSD (79.07%), and critical COA
      (78.57%). Newborns with DDC were more likely to develop symptoms within the first
      few days after birth, in comparison with non-DDC cases. However, their detection
      rates were close to each other. Conclusion: The rate of misdiagnosis of CCHD
      before discharge from maternity hospitals is high in China, indicates the
      importance of implementation of CCHD screening in Chinese maternity hospitals, so
      as to give timely diagnosis and proper treatment.

PMID- 28441822
TI  - [Clinical features and outcomes of radiofrequency catheter ablation of atrial
      flutter in children].
AB  - Objective: To explore the clinical features of atrial flutter (AFL) and evaluate
      the efficacy of radiofrequency catheter ablation (RFCA) for AFL in children.
      Method: Data were collected and analyzed on 50 consecutive pediatric AFL patients
      (male 37/female 13) who underwent electrophysiology study and RFCA from February
      2009 to November 2016 in a case observational study. The average age was (6.2+/
      3.5) years and body weight was (23.7+/-13.5) kg. Heart structure was normal in 26
      patients. Twenty-four patients had congenital heart disease (CHD) and among them
      22 patients underwent repaired surgery before. Patients were followed-up for 1
      month to 7 years after RFCA. Clinical features and the outcomes of RFCA in AFL
      patients were analyzed. Result: The average onset age was (4.2+/-3.3) years. Of
      these patients, 84% had persistent AFL and 16% paroxysmal AFL. AFL with sick
      sinus syndrome (SSS) occurred in 36% patients without statistically significant
      difference between the groups with and without CHD (38.9%(7/18) vs. 61.1%(11/18),
      respectively, P=0.239 5); 49 patients underwent RFCA except one case with atrial
      standstill during the procedure. The total acute success rate was 96%. The follow
      up recurrence rate was 8%.No complication of the procedures was observed. The
      cavotricuspid isthmus-dependent AFL occurred in all patients without CHD.
      However, in the children with CHD after the repair surgery 10 (45%) cases were
      with cavotricuspid isthmus-dependent AFL, 4 (8%) with atrial scars-dependent AFL,
      and 8(16%) with both cavotricuspid isthmus and atrial scars-dependent AFL.
      Conclusion: RFCA was effective and safe for pediatric AFL. There is no difference
      on the acute success rate, the follow-up AFL recurrence rate, as well as
      occurrence of SSS between the groups with and without CHD. AFL patients with CHD
      included the cavotricuspid isthmus-dependent AFL, atrial scars-dependent AFL or
      both.

PMID- 28441823
TI  - [Evaluation of a low dose imaging protocol on radiation exposure reduction in
      pediatric supraventricular tachycardia ablation procedure].
AB  - Objective: To evaluate the feasibility and efficiency of a low dose imaging
      protocol on reducing X-ray dose level in pediatric supraventricular tachycardia
      (SVT) ablation procedure. Method: Data were collected from 103 patients who
      underwent catheter ablation for SVT in Children's Hospital of Fudan University
      from January 2014 to October 2016 in terms of body weight, body surface area
      (BSA), SVT types, accessory pathway location, fluoroscopy time and the radiation
      dose (including AIR KERMA and dose area product) in a case observational
      study.The fluoroscopy protocols were operated at 36 nGy/frame and 10 frames/s
      (Standard group, n=47) from January 2014 to September 2015, 36 nGy/frame and 10
      frames/s with removal of the grid (Grid-out group, n=24) from October 2015 to
      April 2016, as well as 23 nGy/frame and 4.0-7.5 frames/s without the grid (Grid
      out plus low dose group, n=32) from May 2016 to October 2016,
      respectively.Comparisons among groups were performed by independent-sample t-test
      or one-way analysis of variance for normally distributed continuous variables,
      and chi(2) test for categorical variables. Result: The average body weight, BSA,
      fluoroscopy time and AIR KERMA of the three groups was (34+/-14) kg, (1.14+/
      0.33) m(2,) (11+/-8) minutes and (12.97+/-12.43) mGy, respectively.No significant
      differences in body weight (F=2.551), BSA (F=2.359), SVT types (chi(2)=6.15), and
      accessory pathway location (chi(2)=3.438) were observed among these three groups
      (P>0.05). Images acquired by low dose protocol could provide enough information
      for procedures, and no complication occurred.The acute success rates were 100% in
      all of these three groups, and there was no significant difference in mean
      fluoroscopy time (F=0.004, P>0.05) among them.However, the radiation dose (AIR
      KERMA) in the Grid-out plus low dose group was much lower than that in the
      Standard group ((7.54+/-7.31) mGy vs. (16.25+/-12.08) mGy, F=6.112, P<0.01)).
      Conclusion: The new strategy of combination of low dose fluoroscopy protocol with
      removal of grid markedly reduced radiation exposure to children undergoing
      supraventricular tachycardia ablation while maintaining procedural efficacy and
      safety.

PMID- 28441824
TI  - [Clinical and neuroimaging features of acute encephalopathy after status
      epilepticus in Dravet syndrome].
AB  - Objective: To investigate the clinical and neuroimaging characteristics of acute
      encephalopathy (AE) after status epilepticus (SE) of patients with Dravet
      syndrome (DS). Method: The clinical data of DS patients who had AE (coma >=24 h)
      after SE were retrospectively collected from February 2005 to August 2016 in
      Peking University First Hospital and SCN1A gene tests were performed.The clinical
      and neuroimaging features were summarized. Result: Twenty-two patients (9 males
      and 13 females) with AE were collected among 412 DS patients during follow-up.Of
      which 18 patients had SCN1A gene mutations while the remaining 4 patients had no
      SCN1A gene mutations.The onset age of AE was between 6 months and 10 years.The
      duration of SE varied between 40 minutes and 9 hours.Prior to the onset of SE,
      twenty-one patients had high fever, and one patient had normal temperature.Coma
      lasted from 2 days to 20 days.Nine patients died after the AE, and 13 patients
      survived with massive neurological regression.From AE to the last visit, the
      median time of follow-up was 2 years and 3 months (from 7 months to 4 years and 4
      months). Nine of 13 survivors had varied improvement in motor, language and
      cognition, while the remaining 4 patients had no significant improvement.After
      AE, there were 6 patients with seizure-free, 4 patients with reduced seizures,
      and 3 patients with no change in seizure frequency, moreover, spasm occurred in 2
      patients.Six patients had brain magnetic resonance imaging (MRI) in acute phase
      and showed bilateral (2 patients) or unilateral (4 patients) hemisphere edema,
      accompanied by subcortical white matter hyperintense signal in T1 and T2 weighted
      images in two patients.The neuroimaging of 13 survivors demonstrated diverse
      cortical atrophy during recovery phase, among which 4 patients showed cerebellar
      atrophy, one patient had right pontine atrophy, 4 patients accompanied by signal
      abnormalities in subcortical and periventricular white matter, 2 patients showed
      right hippocampal sclerosis, and one patient showed signal abnormalities in
      bilateral basal ganglia. Conclusion: SE is more prone to occur in Dravet patients
      who have high fever.It may result in AE or even death in severe cases.Survivors
      will leave severe neurological sequelae.The neuroimaging shows brain edema in
      acute phase.In recovery phase the neuroimaging shows diverse brain atrophy,
      moreover, a few patients may be associated with cerebellar or pontine atrophy,
      hippocampal sclerosis or abnormal signals in white matter or basal ganglia.

PMID- 28441825
TI  - [Progressive cavitating leukoencephalopathy: four cases and literatures review].
AB  - Objective: To analyze the clinical and genetic features of progressive cavitating
      leukoencephalopathy (PCL). Method: The data of clinical and genetic features of 4
      PCL patients diagnosed by Beijing Children's Hospital between January 2015 and
      January 2016 were analyzed. The cases with complete clinical data retrieved on
      literature search at China National Knowledge Infrastructure, Wanfang Data
      Knowledge Service Platform and PubMed (up to August 2016) by using search terms
      of"NDUFV1" ,"NDUFS1" , or"leukoencephalopathy" , were summarized. Result: There
      were three females and one male, two of which were compatriots. The age of onset
      ranged from 6 months to 15 months. All four children's first symptoms were motor
      development regression, and the developmental milestones were almost normal
      before the onset. Of the 4 patients, 3 had cognitive impairment, 1 had seizures,
      4 had dystonia and pyramidal impairment, 2 had emaciation, and 1 had nystagmus.
      The lactate concentrations of 4 patients were normal in blood. One patient had
      lactaciduria in the urinary organic acid analysis. Cranial magnetic resonance
      imaging (MRI) of all patients showed leukoencephalopathy, involved in the corpus
      callosum, and three patients accompanied by cystic lesions. Follow up for 2-13
      years showed that the physical and language development were improved. Genetic
      analysis revealed that mutations in NDUFS1 were found in three patients and
      NDUFV1 mutation was found in one patient. All six mutations (p.Arg377Cys and p.
      Arg377His in NDUFV1; p. Arg482Glyfs(*)5, p.Thr368Pro, p.Tyr454X and p. Asp565Gly
      in NDUFS1) are novel. Five English case reports including 10 PCL patients were
      collected. Together with this group of 4 cases, a total of 14 cases were
      involved. All 14 children patients had motor development regression, 11 cases had
      cognitive impairment and dystonia, 6 cases had pyramidal impairment, 5 cases had
      irritability, 4 cases had epilepsy and nystagmus, 3 cases had strabismus and
      swallowing difficulty. Cranial MRI showed patchy leukoencephalopathy with
      cavities, involved in the corpus callosum. Follow up for 19 months-15 years that
      the neurology development were improved slowly in all patients. Conclusion:
      NDUFS1 and NDUFV1 gene mutation screening should be performed firstly in patients
      with PCL clinical and imaging feature.

PMID- 28441826
TI  - [A childhood-onset rapid-onset dystonia parkinsonism family with ATP1A3 gene
      mutation and literatures review].
AB  - Objective: To explore clinical characteristics, treatment, and prognosis of a
      family with childhood-onset rapid-onset dystonia parkinsonism (RDP) caused by
      ATP1A3 gene mutation and review literatures. Method: The clinical data of a RDP
      child, his brother and mother had been analyzed retrospectively. This family was
      admitted to Xiangya Hospital in January 2016. DNA samples were analyzed by the
      next-generation sequencing and confirmed by Sanger sequencing. Related literature
      from PubMed, Online Mendelian Inheritance in Man (OMIM), CNKI and Wanfang
      databases to date (up to October 2016) with"Rapid-onset dystonia
      parkinsonism""RDP""DYT12" as key words was reviewed. Result: The proband boy was
      three years and four months old (April 2015) when he had the first attack of the
      disease. After a febricity, he suddenly acquired acute aphasia and limb movement
      disorder. Rehabilitation therapy and supportive treatment made his speech
      gradually recovered but still slurred. However, his abnormal walking posture
      still existed. Nine months later (January 2016, 4 years and one months old),
      symptoms including aphasia, dysphagia, and weakness with rostrocaudal gradient
      reoccured after fever. The disease progressed to the critical condition within 24
      hours. He"seizured" four times with tonic spasms of limbs but without loss of
      consciousness. Family history showed his grandparents were consanguineous
      marriage. His mother and brother also developed abnormal gait and dysarthria
      after an infection before primary school age. Their symptoms improved gradually
      without relapsing. However, they did not recover entirely with mild intellectual
      disability. His mother had a healthy brother and sister. This proband had no
      other siblings but the brother. Heterozygous missense mutation p. R756H in ATP1A3
      gene was detected in this proband, his mother and his brother. This mutation had
      been reported pathogenically related to RDP, and it located in highly conserved
      gene region. Benzodiazepine was used for the proband and his brother, with the
      proband being improved better although not completely. Meanwhile, benzodiazepine
      had no significant effect on his mother because of poor compliance. This is the
      first case report of RDP in China. The mutations of ATP1A3 have been previously
      reported in 51 patients including 6 large families and 16 other unrelated
      patients. A total of 14 different mutations in ATP1A3 gene with RDP have been
      reported to date, including 12 missense mutations, a 3-bp in-frame deletion, and
      a 3-bp in-frame insertion. The sporadic cases all had the typical clinical
      phenotypes of RDP, such as the abrupt onset of dysarthria, dysphagia, limb
      dystonia with bradykinesia, and postural instability. The symptoms of bulbar and
      arms were much more obvious. It was hard to diagnose RDP in a family because some
      patients had typical symptoms of RDP, while the others might experience from mild
      symptoms to no symptoms, which might be related to incomplete penetrance of RDP.
      Two cases carrying the same mutation as our patients also presented some
      overlapping phenotypes. Conclusion: The p. R756H heterozygous mutation in ATP1A3
      gene is the pathogenic mutation of RDP, analysis of genotype-phenotype
      correlations of RDP will be very important and meaningful.

PMID- 28441827
TI  - [Colonization rate of Clostridium Difficile in healthy children].
AB  - Objective: To learn the colonization of Clostridium difficile in local healthy
      children and to investigate the colonization rate and toxin types of Clostridium
      difficile at different ages. Method: From September 2014 to January 2015 in a
      case observational study, healthy children's fecal specimens from the health care
      department of Beijing Children's Hospital were collected. The children were
      divided into four groups according to age: <1 year old(n=53), 1-<3 years
      old(n=50), 3-<6 years old(n=50) and 6-<14 years old(n=50) respectively.
      Polymerase chain reaction (PCR) was used to detect Clostridium difficile toxin
      genes including tcdA, tcdB, binary toxin CDT (cdtA and cdtB), and toxin
      regulatory genes including tcdC, tcdD and tcdE. And then the positive samples
      were sequenced. Measurement data were compared by using t test and rank sum test,
      while, enumeration data were compared using chi-square test. Result: Fifteen
      (7.4%) specimens were positive for Clostridium difficile toxin genes in 203 stool
      specimens. Of the 15 positive specimens, eight(53.3%) were tcdA(+) tcdB(-)(A(+)
      B(-)), four were A(+) B(+) , 3(20.0%) were A(-)B(+) , the binary toxin-positive
      specimens were not detected. TcdC, tcdD, tcdE positive specimens were 8, 6 and
      11, respectively. Gene mutations were not found in positive samples by DNA
      sequencing. In the 15 positive samples, four (7.5%) specimens were in <1 year old
      group; four (8.0%) specimens were in 1-<3 years old group; one(2.0%) specimen was
      in 3-<6 years old group; and 6(12.0%) specimens were in 6-<14 years old group.
      The colonization rate had no significance in different age groups. Conclusion:
      The colonization rate of Clostridium difficile in healthy children was 7.4%. And
      toxigenic Clostridium difficile can be detected in all age groups.

PMID- 28441828
TI  - [Clinical analysis of seven cases of pulmonary malignant tumors in children].
AB  - Objective: To understand the clinical manifestation, imaging characteristics and
      outcomes of pulmonary malignant tumors in children. Method: We retrospectively
      collected information about seven cases of pulmonary malignant tumors in children
      in our hospital from Jan 2010 to Dec 2016. The information included clinical
      manifestation, imaging characteristics, pathologic results, and treatment.
      Result: (1) All the seven patients firstly visited pediatric internal medicine
      departments. Symptoms included cough (n=6), dyspnea (n=4), fever (n=2), anorexia
      (n=2), chest tightness (n=1), chest pain (n=1), lameness (n=1), abdominal
      distension and constipation (n=1). We did not find hemoptysis, wheezing or weight
      loss in those patients. Physical examinations revealed unilateral reduced breath
      sounds (n=5), moist rales and wheezes (n=1), and normal (n=1). Extrapulmonary
      signs included abdominal distension (n=2), left hip tenderness (n=1), and mass in
      left scrotum. We did not identify clubbing finger, anemic appearance, lymph node
      enlargement, or hepatosplenomegaly etc. (2) Laboratory examination results:
      complete blood count showed white blood cells in normal range except one case
      (17.44*10(9)/L). Neutrophil percentage ranged from 0.348 to 0.767. C reactive
      protein ranged between<1 and 162 mg/L. Hemoglobin was normal. Three out of four
      cases had abnormal blood tumor markers.(3) Imaging results showed multiple nodes
      (n=3), multiple cystic lesions in lungs (n=2) (both with pleuropulmonary
      blastoma), endobronchial soft tissue mass (n=1), pulmonary round-shaped mass
      (n=1), and mediastinal mass (n=1). Imaging results also found atelectasis (n=3),
      pneumonia (n=2), pneumothorax (n=2), longitudinal diaphragmatic hernia (n=2),
      pleural effusion (n=1), subcutaneous emphysema (n=1). (4) All the patients
      underwent tumor puncture biopsy or tumor resection. Pathology revealed the final
      diagnosis of pleuropulmonary blastoma (n=3), endodermal sinus tumors (n=2),
      squamous cell carcinoma of lung (n=1), and thyroid papillary carcinoma (n=1). All
      of them were malignant tumors. We followed up them. Two patients died (both with
      pleuropulmonary blastoma) after their parents refused any medical help. Two cases
      were lost to follow-up. Three patients survived (followed up for 19 months, 11
      months and tow months, respectively). One case with thyroid papillary carcinoma
      pulmonary metastasis underwent right thyroid cancer radical plus left thyroid
      lobe resection plus modified selective central lymph node dissection, then iodine
      (131) treatment. One case with endodermal sinus tumor pulmonary metastasis
      underwent three times of chemotherapies, resection of left retroperitoneal tumor
      and left testicular tumor, and six additional chemotherapies. Another one case of
      endodermal sinus tumor pulmonary metastasis underwent three times of
      chemotherapies and was discharged. Conclusion: Pulmonary malignant tumors are
      rare diseases in children. Clinical signs are often non-specific. For those with
      chest CT showing multiple cystic lesions, endobronchial soft tissue mass or
      multiple nodes, but no significant infection manifestation or no response to anti
      infection therapy, pulmonary malignant tumors should be considered. Biopsy may be
      needed to confirm the final diagnosis.

PMID- 28441829
TI  - [Primary ciliary dyskinesia with HYDIN gene mutations in a child and literature
      review].
AB  - Objective: To review children's primary ciliary dyskinesia (PCD) in the
      pathogenesis, clinical manifestation, diagnosis and treatment. Method: To
      summarize and analyze the clinical data of a patient who was admitted to the
      first affiliated hospital of Xiamen University with primary ciliary dyskinesia in
      April 2014 while referring to related literature. Result: An 11 years old boy,
      weighting about 22 kg, had a course of more than 10 years with repeated cough,
      stuffy and runny nose shortly after the birth. Examinations after admission to
      hospital showed that he presented with visible clubbing, bilateral paranasal
      sinus area tenderness, pharynx posterior wall with visible yellow pussy stuff
      drip and bilateral lung had scattered wet rales. Auxiliary examination revealed
      bilateral maxillary sinus, ethmoid sinus inflammation and bronchitis with left
      lower lung bronchiectasis. Fiberoptic bronchoscopy discovered congestion and a
      lot of sputum; ciliary biopsy pathology displayed that cilia were sparse and
      partial cilia 9+ 2 microtubules structural abnormalities. Full sequence of exon
      gene sequencing revealed two mutations located at chromosome 16 chr16: 71061369
      (non-coding regions) and chr16: 70993591 (coding). Two novel mutations m.
      3362A>G(E20) and c. 6101G>A(E39) in exon 16 of the HYDIN gene were identified.
      With the" ciliary motility disorder, gene" as keywords , the CNKI, Wanfang
      digital knowledge service platform and PubMed were searched for relevant articles
      from the establishment to July 2016. The studies retrieved included 9 cases and
      these cases were summarized. Comprehensive analysis showed that HYDIN gene
      mutations related PCD patients had the typical PCD performance such as repeatedly
      wet cough, sinusitis, bronchiectasis, and otitis media. The majority of patients
      have a history of acute respiratory distress syndrome in infancy and no visceral
      dislocation was not found. Most of the patients had no obvious structural
      abnormalities in cilia electron microscopic examination. Conclusion: The PCD
      patients with HYDIN genes mutations have clinical manifestations such as
      sinusitis, otitis media, bronchiectasis but without transposition of viscera.
      Cilia structure can be normal under the electron microscopic examination in some
      of patients.

PMID- 28441830
TI  - [A case of tricho-hepato-enteric syndrome].

PMID- 28441831
TI  - [A case of creatine deficiency syndromes caused by GAMT gene mutation].

PMID- 28441832
TI  - [Fetal cardiac interventions for pulmonary atresia].

PMID- 28441833
TI  - [Research progress of infantile colic].

PMID- 28441834
TI  - [Meeting minutes on kidney session of the 21th Annual Congress of Chinese
      Pediatric Society & the 18th Annual National Conference of Chinese Pediatric
      Nephrology Association].

PMID- 28441835
TI  - [Preconceptional care is pivotal to ensure elderly women safely have two
      children].

PMID- 28441836
TI  - [Clinical value of prenatal MRI in the diagnosis of fetal simple expansion of
      lateral ventricle and follow-up after birth].
AB  - Objective: To explore the value of prenatal MRI in the diagnosis of fetal simple
      expansion of lateral ventricle (ventriculomegaly) , and follow up the nervous
      system development status after birth. Methods: Simple expansion of the lateral
      ventricle fetus by prenatal MRI examination were collected in Huzhou Maternal and
      Child Care Hospital from May 2013 to June 2015, 126 cases of live births in
      expansion group, 50 normal cases were recruited in the same period as the control
      group. In expansion group, fetal subgroup analysis was done: (1) unilateral or
      bilateral lateral ventricle expasion: one group was 98 cases was lateral
      ventricle expansion (77.8%, 98/126), expansion of bilateral ventricle group was
      28 cases (22.2%, 28/126). (2) Prenatal MRI in the diagnosis of the lateral
      ventricle of expansion: expansion of the lateral ventricle width was greater than
      10.0 mm, if both sides were expanding, the expand width was the heavier one side,
      divided into 3 subgroups: 1Expansion in group A (lateral ventricle width 10.0
      12.0 mm) were 88 cases (69.8%, 88/126). 2Expansion in group B (lateral ventricle
      width 12.1-15.0 mm) were 29 cases (23.0%, 29/126). 3Expansion of group C (lateral
      ventricle width> 15.0 mm) were 9 cases (7.12%, 9/126). All 176 cases were
      followed up after birth at the 3rd, 6th, 12th, 18th month (corrected age was used
      for premature babies), and Gesell developmental schedules (GDS) were used to
      evaluate the neurobehavioral development. Results: (1) The MRI results after
      birth: 21 cases were followed up by MRI after birth. In group A, 11 cases had MRI
      and 9 were normal (the ventricular width <10.0 mm after birth), the other 2 cases
      were stable (the ventricular width measured first time after birth was >=10.0 mm,
      but the difference was within 2.0 mm from the MRI before birth). In group B, 4
      cases had MRI, 1 was normal, 1 was stable, and 2 cases were getting better (the
      ventricular width measured first time after birth was >=10.0 mm, but the width
      decreased more than 2.0 mm from the MRI before birth). In group C, 6 cases had
      MRI. 3 cases were getting better and 3 cases were stable. (2) Overall GDS
      results: expansion group after the birth of the 3rd, 6th, 12th, 18th month GDS
      evaluation results compared with control group, respectively, the differences
      were not statistically significant (all P>0.05). (3) The GDS results among the
      subgroups: in each evaluation after birth, there were no statistically
      significant differences between group A and the control group (all P>0.05). The
      GDS results of group B at the 3rd and 6th month were lower than those of the
      control group (P<0.05); while there were no statistically significant differences
      between the 2 goups at the 12th and 18th month (P>0.05). And for group C,
      statistically significant differences were found compared to the control group at
      each follow-up time (all P<0.05). (4) GDS results at different times after birth
      in the expansion group: there was no statistically significant difference between
      the results at the 3rd and 6th month (P>0.05). But when the result at the 3rd
      month was compared to the results of the 12th or 18th month, the differences were
      statistically significant (P<0.05). GDS result of 6th months after birth compared
      with 12th and 18th months, respectively, there were no statistically significant
      differences (P>0.05). There was no statistically significant difference between
      the results at the 12th and 18th month (P>0.05). (5) The GDS results in
      unilateral and bilateral ventricle expansion: at the 18th month, among the 98
      unilateral cases, 86 (87.8%, 86/98) had normal GDS results(>85 scores); 8 (8.2%,
      8/98) had borderline results (75-85 scores); 4 (4.1%, 4/98) had delayed results
      (<75 scores). Among the 28 bilateral cases, 23 (82.1%, 23/28) had normal GDS
      results; 3 (10.7%, 3/28) had borderline results; 2 (7.1%, 2/28) had delayed
      results. There was no statistically significant difference (P>0.05). Conclusions:
      Among the simple expansion of lateral ventricle, those whose ventricular width
      are <=12.0 mm may not need clinical treatment. If the width is between 12.1 to
      15.0 mm, closely follow-up and targeted rehabilitation training after birth are
      recommended. When the width is more than 15.0 mm, the risk of the central nervous
      system function delay is significantly increased, and early intervention might
      improve the prognosis.

PMID- 28441837
TI  - [Characteristics of pre-gestational diabetes mellitus diagnosed during pregnancy
      and the effects on pregnancy outcomes].
AB  - Objective: To analyze the characteristics of pre-gestational diabetes mellitus
      (PGDM) diagnosed during pregnancy (missed diagnosis before pregnancy), and to
      evaluate the effects of diagnostic time on pregnancy outcomes. Methods: A
      retrospective study of 746 pregnant women who were diagnosed PGDM and delivered
      in Peking University First Hospital from January 1st, 2005 to December 31st, 2015
      was conducted. The patients were divided into 2 group. Those diagnosed PGDM
      before pregnancy were defined as Group diagnosed before pregnancy, and those
      diagnosed during pregnancy were defined as Group diagnosed during pregnancy. In
      Group diagnosed during pregnancy, those diagnosed before 24 gestational weeks
      were defined as Group diagnosed during pregnancy A, and those diagnosed after 24
      weeks were defined as Group diagnosed during pregnancy B. The prevalence of
      adverse pregnancy outcomes in each group were analyzed. Results: (1) Rate of
      missed diagnosis for PGDM: the incidence of PGDM diagnosed before pregnancy was
      32.2% (240/746), and those diagnosed during pregnancy (missed diagnosis before
      pregnancy) was 67.8% (506/746). (2) Blood glucose control during pregnancy:
      1Group diagnosed before pregnancy and Group diagnosed during pregnancy: the
      highest glycosylated hemoglobin (HbA1c) in Group diagnosed before pregnancy was
      (6.6+/-1.1)%, higher than that in Group diagnosed during pregnancy [(6.3+/-1.0)%,
      P=0.019]. However, there was no significant difference in the average HbA1c level
      between the 2 groups (P=0.616). The insulin needed percentage [90.8%(218/240) vs.
      53.8%(272/506)] in Group diagnosed before pregnancy were higher than that in
      Group diagnosed during pregnancy (P<0.01). 2Group diagnosed during pregnancy A
      and B: the highest HbA1c in Group diagnosed during pregnancy A was (6.9+/-1.3)%,
      higher than that in Group diagnosed during pregnancy B [(6.1+/-0.8)%, P<0.05].
      And the average HbA1c in Group diagnosed during pregnancy A [(6.4+/-0.8)%] was
      also higher than that in Group diagnosed during pregnancy B [(6.0+/-0.8)%,
      P<0.05]. In Group diagnosed during pregnancy B, 46.1% (187/406) used insulin,
      lower than the percentage in Group diagnosed during pregnancy A (85.0%, 85/100;
      P<0.01). 3There were no significant differences in the highest HbA1c and the
      average HbA1c between Group diagnosed during pregnancy A and Group diagnosed
      before pregnancy (P=0.020, P=0.037). There was neither no significant difference
      in the percentage used insulin during pregnancy between them (P=0.128). There
      were significant differences in the highest HbA1c and the average HbA1c between
      Group diagnosed during pregnancy B and Group diagnosed before pregnancy (P<0.01,
      P=0.014). There was also significant difference in the percentage used insulin
      during pregnancy between them (P<0.01). (3) Pregnancy outcome: 1Group diagnosed
      before pregnancy and Group diagnosed during pregnancy: the cesarean section rate
      [72.5% (174/240) vs. 59.7% (302/506)] in Group diagnosed before pregnancy were
      higher than those in Group diagnosed during pregnancy (P<0.01). However, there
      were no significant differences in preterm birth rate, pre-eclampsia, macrosomia
      percentage, percentage of neonates being hospitalized between the 2 groups
      (P=0.546, P=1.000, P=0.671, P=0.804) . 2There was no significant difference in
      preterm birth rate,cesarean delivery rate, macrosomia percentage, pre-eclampsia
      rate, percentage of neonates being hospitalized between Group diagnosed during
      pregnancy A and Group diagnosed during pregnancy B (P=0.887, P=0.495, P=0.841,
      P=1.000, P=1.000).3There was no significant difference in preterm birth rate,
      cesarean delivery rate, macrosomia percentage, pre-eclampsia rate, percentage of
      neonates being hospitalized between Group diagnosed during pregnancy A and Group
      diagnosed before pregnancy (P=0.875, P=0.093, P=0.662, P=1.000, P=0.837). The
      cesarean delivery rate was lower in Group diagnosed during pregnancy B than that
      in Group diagnosed before pregnancy (P=0.001). However, there were no significant
      differences in preterm birth rate, macrosomia percentage, pre-eclampsia rate,
      percentage of neonates being hospitalized between them (P=0.530, P=0.776,
      P=1.000, P=0.797). Conclusions: The diagnosis of PGDM is commonly missed before
      pregnancy. Fasting plasma glucose should be used as screening test to identify
      PGDM at pre-pregnancy examination or first antenatal care. Using abnormal value
      of 2-hour glucose after 24 gestational weeks as the only way to diagnose PGDM is
      not suitable.

PMID- 28441838
TI  - [Evaluation of endometriosis fertility index in follow-up treatment of
      endometriosis combined with infertility patients after laparoscopic surgery].
AB  - Objective: To explore the application of endometriosis fertility index (EFI) in
      guidance after laparoscopic surgery of endometriosis patients combined with
      infertility and to explore methods to improve pregnancy rate in different EFI
      groups. Methods: A prospective research was done in endometriosis patients
      combined with infertility in Beijing Obstetrics and Gynecology Hospital from
      January 2010 to June 2011, after laparoscopic surgery, these 146 patients were
      divided into 3 groups by EFI score. Using different pregnancy guidance, these
      patients had 5 years follow-up. Results: (1) The 5 years overall pregnancy rate
      was 89.0% (130/146). The pregnancy rate was 95.7% (45/47) in EFI>=9 group, 92.8%
      (77/83) in EFI 5-8 group and 8/16 in EFI<=4 group, three groups were all reach
      satisfactory pregnancy rate; the rate of the first two groups had no
      statistically significance (P=0.498), but had significant difference with the
      last group (P<0.01). (2) In EFI>=5 patients, pregnancy rate was the highest in 6
      months after operation; in EFI>=9 group, the pregnancy rate was 66.7% (30/45),
      and EFI 5-8 group was 50.6% (39/77). (3) EFI>=9 group had the highest natural
      pregnancy rate [83.6% (46/55)], natural pregnancy rate was significant
      statistical different in different EFI groups (P=0.001). Conclusions: EFI score
      is a useful evaluation in predicting and guiding pregnancy in endometriosis
      patients combined with infertility after laparoscopic surgery. EFI score
      guidance, strict post-operation management and positive pregnancy scheme could
      significantly improve the pregnancy rate of endometriosis patients with
      infertility.

PMID- 28441839
TI  - [Detection trend of vaginal intraepithelial neoplasia diagnosed by colposcopy
      guided biopsy from 2013 to 2015].
AB  - Objective: To explore the detection trend of vaginal intraepithelial neoplasia
      (VaIN) of lower genital tract from 2013 to 2015. Methods: A retrospective
      analysis was undertaken of colposcopy-directed biopsy of cervical, vaginal and
      vulvar intraepithelial neoplasia lesions include cervical intraepithelial
      neoplasia (CIN), VaIN and vulvar intraepithelial neoplasia (VIN) in Obstetrics
      and Gynecology Hospital of Fudan University from January 2013 to December 2015.
      Results: (1) Overall data of CIN, VaIN and VIN: a total of 16 732 cases were
      diagnosed of lower genital intraepithelial neoplasia in 3 years, accounting for
      23.20% (16 732/72 128) of total colposcopy-directed biopsy cases. Among them,
      CIN, VaIN and VIN accounted for 19.48% (14 053/72 128), 2.67% (1 923/72 128),
      1.05% (756/72 128) of total colposcopy-directed biopsy cases of the lower genital
      tract, 83.99% (14 053/16 732), 11.49% (1 923/16 732), 4.52% (756/16 732) of total
      lower genital intraepithelial neoplasia, respectively. (2) Annual data of CIN,
      VaIN and VIN from 2013 to 2015. The annual proportion of CIN in all
      intraepithelial neoplasia of lower gential tract was basically stable, consisting
      of 86.02%(3 955/4 598),83.25%(4 795/5 760) and 83.20% (5 303/6 374),
      respectively. The annual proportion of VaIN was gradually increasing, consisting
      of 8.09%(372/4 598), 12.45%(717/5 760) and 13.08%(834/6 374), respectively. The
      annual proportion of VIN was gradually decreasing, consisting of 5.89%(271/4
      598), 4.31%(248/5 760) and 3.72%(237/6 374), respectively. Conclusion: The
      increasing detection of VaIN from 2013 to 2015 might correlate with the
      increasing attention to inspection of the entire vaginal wall.

PMID- 28441840
TI  - [Atypical polypoid adenomyoma of the uterus: a clinicopathological review of 27
      cases].
AB  - Objective: To investigate the clinical and pathological characteristics of
      atypical polypoid adenomyoma (APA) for improvement of the diagnosis, different
      diagnosis and treatment of the disease. Methods: The clinical data, pathological
      characteristics, and the follow-up information were retrospectively analyzed in
      27 cases of APA admitted in Peking Univeristy People's Hospital from 2007 to
      2016. Results: The median age was 42.6 years old (range 25-60 years old). Fifteen
      patients were nullipara, 2 patients were postmenopausal. The most common
      presenting symptom was abnormal uterine bleeding (81%, 22/27) . Leisions were
      obtained by using hysteroscopy in 23 cases, hysterectomy 3 cases and dilatation
      and curettage 1 case. Fertility preserving treatments were performed in 10
      patients who had strong desire for fertility, among which 1 case progressed into
      endometrial carcinoma. Among 15 patients underwent hysterectomy and (or)
      bilateral salpingo-oophorectomy, 9 cases of them had endometrial atypical
      hyperplasia. Endometrial carcinoma along with APA were found in three patients, 2
      cases of them underwent hysterectomy and bilateral salpingo-oophorectomy and
      pelvic lymphadenectomy, the other one received medication for fertility
      preservation. Follow up information were available in 24 cases (89%, 24/27) with
      a median follow up of 46 months (range 4-108 months), 1 case recurred and 1 case
      progressed into endometrial carcinoma. One case died of other malignancy, while
      the other patients were alive. Conclusions: APA is a rare uterine neoplasm mixed
      with epithelial and mesenchymal component. It occurs mostly in childbearing-age
      women and its diagnosis is dependent on pathology. Although it's clinical course
      is benign, there is risk of co-existance of endometrial carcinoma and endometrial
      atypical hyperplasia. For those who has desire of fertility, the treatment
      strategy is completely removed the lesion and closely followed up. For those who
      do not desire to preserve fertility, hysterectomy may be an option.

PMID- 28441841
TI  - [An experiment control study on the ovarian reserve function after cisplatin
      intraperitoneal or intravenous chemotherapy in rats model].
AB  - Objective: To compare the impact on the ovarian reserve function after cisplatin
      intraperitoneal or intravenous chemotherapy in rats model. Methods: Thirty 8
      weeks old female Sprague Dawley rats were randomly assigned to control group
      (group A, n=10), intraperitoneal chemotherapy group (group B, n=10) and
      intravenous chemotherapy group (group C, n=10). Cisplatin was diluted by normal
      saline (NS) into 4 mg/ml. On the first day of chemotherapy, 0.2 ml cisplatin
      dilution was injected into the abdomen of rats in group B, isodose cisplatin was
      injected into vein and 1.8 ml NS was injected into abdomen of rats in group C,
      2.0 ml NS was injected into abdomen of rats in group A for control. Feed the
      three groups rats and test the anti-Mullerian hormone (AMH) in serum on day 0
      (just before injection), day 10 and day 20 by ELISA, count the numble of follicle
      in bilateral ovaries on day 20. Results: (1) The levels of serum AMH in the three
      groups before and after chemotherapy were compared: 1 comparison between groups:
      On day 10 and day 20, the AMH level in group B [(64.5+/-2.9), (68.6+/-3.4) ng/L]
      and group C [(76.1+/-4.9), (91.3+/-3.9) ng/L] was significantly lower than that
      in group A [(120.1+/-5.3), (121.7+/-4.6) ng/L; P<0.01], AMH level in group B was
      significantly also lower than that in group C (P=0.000). 2 Comparison within
      groups: the AMH level on day 0 was significantly lower than that on day 10 and
      day 20 in group A (P<0.01), but there was no significant difference between day
      10 and day 20 (P=0.427). The AMH level on day 0 was significantly higher than
      those on day 10 and day 20 in group B (P<0.01) and group C (P<0.01). There was no
      difference in AMH level between day 10 and day 20 (P=0.124) in group B, but the
      level was significant lower on day 10 than that on day 20 in group C (P=0.011).
      (2)Comparison of the number of follicles in ovaries of three groups 20 days after
      chemotherapy: the follicles number in group A (35+/-13) was greater than that in
      group B (16+/-9, P=0.003) and similar with group C (31+/-16, P=0.474) on day 20.
      The follicles number in group B was significantly less than that in group C
      (P=0.018). Conclusions: In the present study, both intravenous and
      intraperitoneal chemotherapy have impacts on ovarian reserve function and the
      latter might be more serious. The level of AMH will rise again over time after
      chemotherapy and rats undergo intravenous chemotherapy would recover faster. The
      results suggest that the ovarian reserve function need more time to recover after
      intraperitoneal chemotherapy. For patients with ovarian cancer who want to
      preserve fertility function, intravenous chemotherapy might be more appropriate.

PMID- 28441842
TI  - [Analysis of funding of projects on obstetrics and gynecology supported by
      National Natural Science Foundation of China from 2007 to 2016].
AB  - Objective: To summarize the funding of scientific research projects on obstetrics
      and gynecology by National Natural Science Foundation of China (NSFC) from 2007
      to 2016 and to display the hotspots of scientific research on obstetrics and
      gynecology. Methods: A systemic search was performed for the information of
      projects supported by NSFC from 2007 to 2016. The indicators for analysis
      included the number of projects, total investment, project categories, research
      units and research field. The research direction of each project was decided
      based on title, summary and key words provided by the profile of each project.
      Results: The total investment on obstetrics and gynecology by NSFC was 23.214
      million with a total of 82 projects in 2007. It increased year by year and
      reached the peak in 2014 (359 projects 208.990 million). The investment and
      number of projects remained stable after 2014. General projects (1 109 projects
      608.000 million) formed the majority of projects. Youth science fund projects (1
      035 projects 214.976 million) increased steadily and the number was nearly equal
      to general projects. There were only a small amount of key projects (20 projects
      54.720 million) and major projects (7 projects 38.400 million). The investment
      varied in different research units. The greatest 10 units (less than 6% of
      total), including 7 comprehensive universities, 2 medical universities and 1
      institute of medicine, got 1 113 projects invested (43.84% of total, 1 113/2
      539). The hot areas like gynecological tumor (920 projects 350.615 million),
      hypertensive disorders complicating pregnancy (91 projects 37.470 million) and
      polycystic ovarian syndrome (77 projects 29.540 million) were more likely to
      receive investment, while some interdisciplinary science like maternal and child
      health (28 projects 12.050 million), imaging and biomedicine (37 projects 14.770
      million) began to achieve attention in recent years. Conclusions: The number of
      researches invested will be increased for the scientific research in obstetrics
      and gynecology especially the areas of research focus, although the amount
      allocated for each will be decreased relatively. Besides, multidisciplinary work
      will be performed so as to develop obstetrics and gynecology of China to a high
      level.

PMID- 28441844
TI  - [Is epicardial pacing lead always a substitute?]

PMID- 28441843
TI  - [Three-dimensional printing technology in the cardiac field: prospects and
      challenges].

PMID- 28441845
TI  - [Personal evaluation on gene test to prevent birth defects].

PMID- 28441846
TI  - [Surgical treatment of traumatic biliary stricture].

PMID- 28441847
TI  - [Feasibility of device closure for multiple atrial septal defects using 3D
      printing and ultrasound-guided intervention technique].
AB  - Objective: To investigate the feasibility of trans-catheter closure of multiple
      atrial septal defects (ASD) monitored by trans-thoracic echocardiography (TTE)
      under the guidance of 3D printing heart model. Methods: Between April and August
      2016, a total of 21 patients (8 male and 13 female) with multiple ASD in Fuwai
      Hospital of Chinese Academy of Medical Sciences underwent CT scan and 3
      dimensional echocardiography for heart disease model produced by 3D printing
      technique. The best occlusion program was determined through the simulation test
      on the model. Percutaneous device closure of multiple ASD was performed follow
      the predetermined program guided by TTE. Clinical follow-up including
      electrocardiogram and TTE was arranged at 1 month after the procedure. Results:
      The trans-catheter procedure was successful in all 21 patients using a single
      atrial septal occluder. Mild residual shunt was found in 5 patient in the
      immediate postoperative period, 3 of them were disappeared during postoperative
      follow-up. There was no death, vascular damage, arrhythmia, device migration,
      thromboembolism, valvular dysfunction during the follow-up period. Conclusion:
      The use of 3D printing heart model provides a useful reference for transcatheter
      device closure of multiple ASD achieving through ultrasound-guided intervention
      technique, which appears to be safe and feasible with good outcomes of short-term
      follow-up.

PMID- 28441848
TI  - [Short-term clinical outcomes and risk factors associated with in-hospital
      mortality in patients undergoing off-pump coronary artery bypass grafting].
AB  - Objective: To explore short-term clinical outcomes and risk factors associated
      with in-hospital mortality in patients undergoing off-pump coronary artery bypass
      grafting (OPCABG) and establish a prediction model for in-hospital mortality.
      Methods: The clinical data of patients undergoing OPCABG in Beijing Anzhen
      Hospital between January 2014 and January 2016 was retrospectively studied.
      Univariate analysis and logistic regression were applied to determine the
      potential risk factors, and then a prediction model for mortality was confirmed.
      The calibration and discrimination of the prediction model was finally tested.
      Results: A total of 2 546 patients who underwent OPCABG were recruited. In
      hospital mortality of OPCABG was 0.7% (17 cases). Seven variables: female, age,
      left main disease >50%, low left ventricular ejection fraction (LVEF), acute
      myocardial infarction before surgery, operative status (selective or emergent),
      moderate concomitant mitral valve regurgitation were independently correlated
      with OPCABG mortality (all P<0.05). The result of Hosmer-Lemeshow test was
      chi(2)=5.912, P=0.676. The area under receiver-operating characteristic curve
      (ROC) was 0.881. Conclusions: OPCABG is safe and effective for myocardial
      revascularization in a short term. The following risk factors are associated with
      an increased operative mortality of OPCABG: male, age, left main disease >50%,
      low LVEF, acute myocardial infarction before surgery, operative status (selective
      or emergent), moderate concomitant mitral valve regurgitation. The prediction
      model established by above-mentioned potential risk factors was proven to perform
      well by statistical tests.

PMID- 28441849
TI  - [Feasibility and effectiveness of percutaneous ventricular septal defect closure
      under solely guidance of echocardiography].
AB  - Objective: To compare the efficacy and safety of percutaneous ventricular septal
      defect (VSD) closure under solely guidance of echocardiography and fluoroscopy.
      Methods: The retrospective study was conducted at Fuwai Hospital, between
      February 2014 and February 2015. The patients were divided into two groups. VSD
      closure was conducted in 42 patients under solely guidance of echocardiography,
      and 100 patients who were treated with percutaneous catheter closure under
      fluoroscopy guidance were selected as a control group. The baseline
      characteristics, procedural time and complications were recorded and assessed.
      Results: There were no significant differences in terms of age, gender and pre
      operative echocardiographic characteristics (all P>0.05). Percutaneous VSD
      closure under traditional fluoroscopy guidance was successful in 95 patients
      (95%). The procedural time was (54.7+/-12.5) minutes. The symmetrical occluders
      diameter was (6.9+/-1.8) mm. Four patients had postoperative residual shunt, one
      patient developed left bundle branch block, and 6 patients developed new
      tricuspid regurgitation. Percutaneous VSD closure under only transthoracic
      echocardiography (TTE) guidance was successful in 39 patients (93%). Because of
      delivery catheter passage failure through the defect, one case required
      conversion to perventricular closure via a small transthoracic incision under
      transesophageal echocardiography (TEE) guidance. The other two cases underwent
      surgical repair because of residual shunt with more than 2 mm after closure. The
      procedural time was (40.3+/-13.2) minutes. The symmetrical occluders diameter was
      (6.5+/-1.2) mm. Four patients had postoperative residual shunt that disappeared
      after 1 month follow-up, and one patient developed right bundle branch block
      which disappeared 3 days later. During (9.3+/-3.6) months follow-up, there were
      no other complications, such as pericardial effusion, occluder malposition,
      atrioventricular block, aortic valve regurgitation, and aggravating tricuspid
      regurgitation in each group. However, the total operation time, diameter of VSD
      occluder, total mild complications, and the equipment cost in the study group
      were less than that in the control group (P<0.05). Conclusion: Percutaneous VSD
      closure can be successfully performed under sole guidance of echocardiography
      with outcomes similar to those achieved with fluoroscopy guidance.

PMID- 28441850
TI  - [Clinical application of one-stage operation of epicardial permanent pacemaker
      implantation and cardiac surgery].
AB  - Objective: To summarize the results and clinical application experience of one
      stage operation of epicardial permanent pacemaker implantation and cardiac
      surgery. Methods: From November 2014 to July 2016, 15 patients (9 males and 6
      females) with ages ranging from 50 to 73 (63.5+/-6.2) years requiring cardiac
      surgery with bradycardia underwent one-stage operation of epicardial permanent
      pacemaker implantation and cardiac surgery. All operations were performed under
      general anesthesia with chest median incision approach. Among them, single
      chamber pacemaker (n=10) and dual chamber pacemaker (n=5) permanent epicardial
      pacing leads were implanted. Simultaneous procedures included valve replacement
      in 7 cases, valve replacement combined with atrial fibrillation ablation in 3
      cases, coronary artery bypass grafting in 2 cases, aortic root replacement in 2
      cases, and valve replacement combined with coronary artery bypass surgery in 1
      case. Their parameters of pacemaker including sensitivity, pacing threshold,
      pacing impedance were measured during surgery and closely followed up at 1 week
      and 3, 6 months after surgery. Results: All 15 patients with epicardial permanent
      pacemaker implantation in the same period of cardiac surgery were successfully
      cured and discharged, without any surgical complications. A total of 20
      epicardial electrodes were implanted for them including 5 right atrial electrodes
      and 15 right ventricular electrodes. The postoperative follow-up period ranged
      from 3 to 22 months. No electrode fracture and surgical wound infection occurred
      in those patients, and their impedance, sensing and stimulation thresholds were
      all in normal ranges during follow-up. Conclusions: For patients with bradycardia
      who required cardiac surgery, one-stage operation of epicardial permanent
      pacemaker implantation and cardiac surgery is safe and effective, and the results
      in the short-term and medium-term are satisfactory, avoiding the risk of staged
      surgery.

PMID- 28441851
TI  - [Quantities and function of NK cells in patients with immune thrombocytopenia].
AB  - Objective: To investigate natural killer (NK) cell quantities and function in
      patients with immune thrombocytopenia (ITP) . Methods: A total of 66 ITP patients
      (34 newly diagnosed and 32 in complete remission) were collected from September
      2015 to May 2016 in Tianjin Medical University General Hospital, and 30 healthy
      volunteers were recruited as controls. The percentages of NK cells and their
      subsets in peripheral blood, the expression of activating receptor (NKp44),
      inhibitory receptor (NKG2A) and CD16, perforin and granzyme beta were detected by
      flow cytometry. The correlation between the above parameters and patients' immune
      status and platelet level were evaluated. Results: (1)The percentage of CD3(
      )CD56(+) NK cells in newly diagnosed patients (10.99%+/-4.89%)and patients in
      complete remission (9.73%+/-6.75%) were significantly lower than that in healthy
      controls (14.67%+/-7.24%)(P=0.023, 0.003). The percentage of NK cells Bright
      subset was significantly lower in the newly diagnosed patients(0.48%+/-0.23%)and
      those in complete remission (0.41%+/-0.33%) than in healthy controls(0.64%+/
      0.32%)(P=0.037, 0.002); the percentage of Dim subset was also significantly lower
      in the newly diagnosed (10.16%+/-5.02%) and patients in complete remission
      (8.07%+/-5.74%) than in healthy controls(14.16%+/-7.19%) (P=0.009, 0.007). (2)The
      proportion of Bright subset in total NK cells in new diagnosed ITP patients
      (6.48%+/-4.33%) was significantly higher than that in healthy controls (4.21%+/
      2.70%)(P=0.020); the proportion of Dim NK cells subset in new diagnosed ITP
      patients (93.51%+/-4.33%) was significantly lower than that in healthy
      controls(95.79%+/-2.70%) (P=0.020). (3)The expression of activating receptor
      NKp44 in new diagnosed ITP patients was significantly lower than that in complete
      remission group and healthy controls[0.28%(0.95%)vs 0.61%(2.05%), 0.92%(0.90%);
      P=0.047, 0.048]; the expression of inhibitory receptor NKG2A in new diagnosed ITP
      patients was significantly higher than that in healthy controls(42.34%+/-23.86%
      vs 29.25%+/-12.83%, P=0.009). The proportion of CD16 was significantly lower in
      the newly diagnosed patients than in healthy controls(93.51%+/-4.33%95.79%+/
      2.70%, P=0.020). (4)The expression of perforin in the newly diagnosed ITP
      patients was significantly lower than that in healthy controls [87.52%(25.29%)vs
      91.55%(8.29%), P=0.025]; the expression of granzyme beta in ITP patients and
      controls showed no statistically significant difference. (5)The level of NK cells
      in ITP patients was negatively correlated with CD3(+) CD8(+) T cells (r=-0.387,
      P=0.012) and CD5(+) CD19(+) B cells in peripheral blood (r=-0.273, P=0.028),
      positively correlated with the ratio of CD3(+) CD4(+) /CD3(+) CD8(+) (r=0.358,
      P=0.028) and peripheral platelet count (r=0.314, P=0.011). Conclusion: Deceased
      quantities and impaired total NK function, insufficient suppression of
      autoreactive T and B cells might play a role in the pathogenesis of ITP.

PMID- 28441852
TI  - [Clinical presentation of Kleine-Levin syndrome].
AB  - Objective: To analyze the clinical features of Kleine-Levin syndrome (KLS)
      patients. Methods: Clinical data of 44 patients with KLS of the Sleep Center of
      Peking University People's Hospital from January 2002 to July 2013 were
      systematically reviewed. The predisposing factors and clinical presentations were
      summarized, and compared with the data from a Western KLS study with a large
      subjects number. Nocturnal polysomnography (PSG) and multiple sleep latency test
      (MSLT) were conducted during relapse and remission period, respectively. HLA
      DQB1*0602 gene were screened and analyzed. Results: Among the 44 patients,
      28(63.6%) were men and 16(36.4%) were women, with a mean age of (18.3+/-8.9)
      years old. Most patients developed the symptoms during adolescence. Infection or
      fever was the most common trigger for episode. The main clinical presentations
      were 44(100.0%) hypersomnia, 31(70.5%) forgetfulness, 26(59.1%) decreased
      appetites, 24(54.5%) juvenile behavior, 18(40.9%) depression, etc. Compared with
      the Western study, it showed that our patients had decreased instead of increased
      appetite. The PSG testing did not have remarkable findings. MSLT showed mean
      sleep latency was significantly shorter during relapse than during remission
      [(10.4+/-5.4) vs (15.3+/-3.4) min, P=0.009]. HLA-DQB1*0602 was positive in 12 of
      40(30.0%) patients, which was similar to the data in the Chinese population.
      Conclusions: KLS has various clinical characteristics. The presentation of
      appetite may be different between Chinese and western KLS patients.

PMID- 28441853
TI  - [Differentially expressed genes analysis in expression profile data of pulmonary
      fibrosis with pulmonary hypertension].
AB  - Objective: To analyze the differential gene expression of patients with
      idiopathic pulmonary fibrosis and pulmonary hypertension (IPF-PH). Methods: The
      expression profile data of GSE15197 was downloaded from the Gene Expression
      Omnibus (GEO) database. Bonferroni algorithm was used to identify the
      differentially expressed genes of pulmonary tissues from IPF-PH, idiopathic
      pulmonary arterial hypertension (IPAH) and Normal groups. Principal component
      analysis was used to extract the principal components of three types of samples
      and differentially expressed genes were obtained. Gene annotation and gene
      association analysis were used to analyze gene function and related signaling
      pathways. Results: Gene expression profiles of pulmonary tissues from IPF-PH,
      IPAH and Normal groups were compared and analyzed, and 160 differentially
      expressed genes were found (P<0.05). Nine principal component were found with the
      cumulative contribution rate of >0.85, and there were 44 significant differences
      genes with the loading coefficient >80% in principal component one, which was
      mainly related to the expression of cilium, gamma-glutamyltransferase, and
      phospholipase. The signaling pathway of differential expression genes were mainly
      involved in the biosynthesis of leukotriene biosynthetic process and gamma
      glutamyltransferase activity. Conclusion: The differential gene expression and
      their functional annotation can provide important clues for the pathogenic genes
      of IPF-PH, and may provide a theoretical basis for exploring potential biomarkers
      and drug targets.

PMID- 28441854
TI  - [Correlation between anatomical factors of spermatic vessels and varicocele].
AB  - Objective: To analyze the correlation between anatomy of spermatic vessels and
      varicocele, providing reference for the preoperative assessment and treatment of
      varicocele. Methods: A total of 156 patients who underwent microsurgical left
      subinguinal varicocelectomy at Shanghai General Hospital between May 2015 and
      July 2016 were included in this study. The severity of varicocele and number of
      spermatic vessels detected in operations were recorded. According to the number
      of internal spermatic arteries (ISAs), the patients were divided into three
      groups: single-ISA group (55 cases), double-ISAs group (63 cases) and multi-ISAs
      group (38 cases), to analyze the correlation among spermatic vessels and to
      compare varicocele grade, the volume of testes, the parameter of semen analysis,
      serum reproductive hormone, surgery time, and hospital stay among the three
      groups. Results: The number of ISAs was positively correlated with the
      ipsilateral internal spermatic veins (ISVs) (r=0.210; P=0.008)and lymphatic
      vessels (r=0.224; P=0.005); the number of lymphatic vessels was positively
      correlated with the ipsilateral gubernacular veins (r=0.172; P=0.032)and ISVs
      (r=0.296; P=0.000) . The number of ISVs in the multi-ISAs group (10.58+/-4.28)
      was significantly larger than that in the single-ISA group (8.22+/-3.10,
      P=0.003). The number of lymphatic vessels in the multi-ISAs group(4.11+/-1.90)was
      also significantly larger than that in the double-ISA group(3.76+/-1.40, P=0.020)
      and the single-ISA group(3.13+/-1.52, P=0.007). The number of ISVs in grade 2
      varicocele patients (9.74+/-3.90) was significantly higher than that in grade 3
      varicocele patients (8.33+/-3.10, P=0.013). No significant differences in
      varicocele grade, change of pre- and post-operative semen analysis, serum
      reproductive hormone, the volume of ipsilateral testes, surgery time, and
      hospital stay were observed among the three groups. Conclusions: There is a
      correlation among various kinds of spermatic vessels. Patients with grade 2
      varicocele, especially who have multiple ISAs, are likely to have more ISVs and
      lymphatic vessels. For these patients, surgeons should pay more attention to
      protect spermatic arteries and lymphatics carefully while ligating varicose veins
      completely to prevent recurrence and complications.

PMID- 28441855
TI  - [Correlation between mismatch repair proteins status and clinicopathological
      characteristics in sporadic colorectal cancer patients].
AB  - Objective: To explore the expression of mismatch repair (MMR) proteins in
      sporadic colorectal cancer (SCRC) patients, and its association with
      clinicopathological characteristics of SCRC. Methods: Patients with
      histologically confirmed colorectal cancer were consecutively recruited between
      December 2011 and June 2015 at Sun Yat-sen University Cancer Center. The
      exclusion criteria included multiple primary colorectal tumors, hereditary
      colorectal cancer (including Lynch syndrome, familial adenomatous polyposis), and
      the patients without the MMR proteins status tested. A total of 2 684 patients
      were included. Correlations of MMR proteins status and patients' demographics
      (including gender, age), tumor characteristics (site and differentiation) and TNM
      staging (excluding 315 SCRC patients receiving neoadjuvant therapy) were
      investigated. Results: The percentage of deficient MMR (dMMR) in these SCRC
      patients was 10.2%, and that of proficient MMR (pMMR) was 89.8%. The dMMR was
      more likely to be detected in younger (<=59 old years) SCRC patients compared to
      the elderly (>59 years) [12.7%(179/1 406)vs 7.5%(96/1 278), P<0.001]. The dMMR
      rate in right colon cancer was significantly higher than that in left colon
      cancer and rectal cancer [22.7%(151/664)vs 7.2%(69/956)vs 5.2%(55/1 064),
      P<0.001]. Among the various pathological types of SCRC, mucinous adenocarcinoma
      showed the highest rate of dMMR (24.4%), and neuroendocrine carcinoma the lowest
      rate of dMMR (0) (P<0.001). In addition, the proportions of dMMR in stage I,
      stage II, stage III and stage IV SCRC were 9.7%, 16.5%, 8.5%, and 3.9%,
      respectively (P<0.001). There is no significant difference in the proportion of
      dMMR between male and female (11.0% vs 9.1%, P=0.114). Conclusion: dMMR status
      may be most likely to exist in younger (<=59 years) patients with stage II right
      colon mucinous adenocarcinoma among SCRC.

PMID- 28441856
TI  - [Clinical value of the early use of ulinastatin in patients with moderately
      severe or severe acute pancreatitis].
AB  - Objective: To observe the clinical efficacy and the effects on serum inflammatory
      factors of early use of ulinastatin in patients with moderately severe or severe
      acute pancreatitis (MSAP/SAP). Methods: This prospective, randomized, controlled
      trial was conducted in the First Affiliated Hospital of Soochow University from
      September 2013 to May 2016. A total of 42 cases were enrolled and assigned into
      either observation group or conventional treatment group (n=21 each). The
      conventional treatment group received somatostatin, while the observation group
      received somatostatin combined with ulinastatin. After treatment, clinical
      characteristics, serum indicators, clinical complications and serum level of
      inflammatory factors were analyzed. Results: Intra-abdominal pressure and relief
      time of abdominal pain were significantly decreased in observation group [
      (10.4+/-2.1) cmH(2)O; (2.5+/-1.2) d ] compared with the conventional treatment
      group [ (11.7+/-2.2) cmH(2)O; (3.33+/- 1.2) d ], P<0.05. White blood cells (WBC)
      were lower in observation group than those in conventional treatment group [
      (11.2+/-1.8) *10(9)/L vs (12.5+/-2.3) *10(9)/L; P<0.05 ]. After treatment serum
      levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha(TNF-alpha)
      in observation group [ (30.5+/-3.3), (34.7+/- 6.5), (22.6+/-4.0) MUg/L] were
      significantly lower than those in conventional treatment group [ (39.6+/-4.0),
      (40.9+/-3.4), (33.1+/-6.6) MUg/L], P<0.05. There were no differences between the
      two groups in modified CT severity index (MCTSI), recovery time of defecation,
      ICU length of stay, serum amylase, C-reactive protein (CRP) and incidence rates
      of clinical complications. Conclusions: The early use of ulinastatin in the
      patients with MSAP/SAP can down-regulated the levels of TNF-alpha, IL-6 and IL-8,
      reduce the inflammatory response, decrease intra-abdominal pressure and shorten
      abdominal pain time. It was beneficial and worthy of wider popularization.

PMID- 28441857
TI  - [Clinical exploratory application of robotic resection of tumor in segment VIII:
      a report for 7 cases].
AB  - Objective: To investigate the feasibility and security of robotic resection of
      tumor in segment VIII primarily. Methods: The clinicopathologic data of 7
      patients who underwent robotic resection of tumor in segment VIII using daVinci
      robotic system in the Department of Hepato-pancreato-biliary Surgical Oncology,
      Chinese PLA General Hospital from June 2016 to December 2016 were retrospectively
      analyzed. The lesion size, the tumor malignance degree mean operation time,
      intraoperative blood loss and the rate of conversion to laparotomy, postoperative
      hospital stay, mobidity and motality of all the 7 patients were collected.
      Results: All the 7 operations were successfully performed with radical
      resection.The mean tumor diameter was (4.6+/-1.2)cm. The mean operation time,
      intraoperative blood loss and postoperative hospital stay were(120.7+/-21.7)min,
      (100+/-106.7)ml, and(7.3+/-1.8)days respectively.All the patients were discharged
      successfully with no severe complications. Conclusions: According to our
      experiences, as a new operationmodel of minimally invasive surgery, robotic
      resection of tumor in segment VIII has manyadvantages in laparoscopic like less
      trauma, less intraoperative bleeding, light postoperative pain, shorter
      postoperative hospital stay and so on. There are some certain advantages in
      exposure of VIII segment under robotic surgery system. Robotic surgery system is
      safe and feasible for tumorresection of segmentVIII, andhas clinical promoting
      value and application prospect.

PMID- 28441858
TI  - [Development of an eosinophilic bronchitis mouse model and the effects of
      eosinophil activation on airway hyperresponsiveness in eosinophilic bronchitis
      mice].
AB  - Objective: To develop a mouse model of eosinophilic bronchitis, and explore the
      effects of eosinophil activation on airway hyperresponsiveness. Methods: A total
      of 60 female specific pathogen free BALB/c female mice were divided randomly into
      four groups: polymyxin B group, normal saline group, polymyxin B+ N-methionine
      leucine phenylalanine (fMLP) group, normal saline+ fMLP group. All the groups
      were given corresponding nasal drops for 21 days. The former two groups were
      given 12 MUl 0.5% polymyxin B or normal saline once a day by transnasal
      administration respectively. Besides the above, the latter two groups were given
      10 MUl fMLP (0.05 mg/ml, dissolved in acetic acid) once by transnasal
      administration 3 hours after polymyxin B or normal saline administration on the
      21st day. Within 24 hours after the last transnasal administration, cells in
      bronchoalveolar lavage fluid (BALF) were collected and analyzed by absolute
      different cell counts. Airway responsiveness (inspiratory and expiratory airway
      resistance and lung compliance) to acetyl choline (Ach) were measured 3 hours
      after the last transnasal administration in the former two groups and 24 hours
      after the last transnasal administration in the latter two groups. Eosinophil
      peroxidase (EPX), eosinophil cationic protein (ECP) and eosinophil chemotactic
      factor (ECF) levels in serum, BALF and lung tissue were tested by emzyme linked
      immunosorbent assay (ELISA). HE and Chromotrope 2R staining of lung tissue were
      used to observe the infiltration of inflammatory cells. The morphology of low
      density eosinophils was observed under electron microscope. Results: The total
      cell counts of BALF in polymyxin B group were significantly higher than the
      normal saline group [29.50 (3.25)*10(4)/ml vs 15.25 (2.25)*10(4)/ml, P<0.001],
      especially eosinophil counts [11.76 (6.02)*10(4)/ml vs 0.12 (1.08)*10(4)/ml,
      P<0.001]. However, no significant differences of inspiratory and expiratory
      airway resistance and lung compliance existed in the two groups. Inspiratory and
      expiratory airway resistance in polymyxin B+ fMLP group were significantly
      higher, lung compliance significantly lower than those in the other three groups
      (all P<0.001), and the EPX, ECP, ECF levels in serum, BALF and lung tissue of the
      polymyxin B+ fMLP group were significantly higher than the other three groups
      (all P<0.001). There were more inflammatory cells, especially eosinophils in lung
      tissue of polymyxin B and polymyxin B+ fMLP group. Meanwhile, more activated
      eosinophils in polymyxin B+ fMLP group were observed by electron microscopy.
      Conclusion: A mouse model of eosinophilic bronchitis can be successfully
      developed by transnasal administration of polymyxin B, and the eosinophil
      activation plays an important role in the occurrence of airway
      hyperresponsiveness.

PMID- 28441859
TI  - [DNT cell inhibits the growth of pancreatic carcinoma via NKG2D and MICA pathway
      in vivo].
AB  - Objective: To investigate the effects of natural killer group 2 member D (NKG2D)
      and its ligands major histocompatibility complex class I chain-related molecules
      A(MICA) on DNT cell killing pancreatic carcinoma. Methods: Antibodies adsorption
      was used to separate DNT cell from human peripheral blood. Human pancreatic tumor
      models were established via implanting BXPC-3 cells into nude mice, and then mice
      were randomly divided mice into 3 groups, blank group, gemcitabine group and DNT
      group. Mice weights and mice tumor volumes were measured every 5 days. After 40
      days mice were euthanized at cervical dislocation method. Tumor weights were
      measured. Relative tumor volume and tumor inhibition rate were calculated.
      Western blot and qPCR were used to detect the expressions of NKG2D and MICA in
      the transplanted tumors of the three groups. Results: The blank group tumor
      volume and weight of blank group were significantly larger than those of
      gemcitabine group and DNT group (858.7+/-35.7 mg, 251.1+/-19.7 mg, 278.5+/-17.3
      mg, P<0.001), but there were no significantly difference between DNT group and
      gemcitabine group. The tumor inhibition rate of gemcitabine and DNT cell were
      40.4% and 35.5%. Western blot and qPCR showed that MICA mRNA and protein levels
      in blank group were significantly higher than those in DNT group (P=0.001,
      P=0.003). NKG2D mRNA and protein levels in blank group were significantly lower
      than those in DNT cells group (P<0.001, P=0.001). Conclusion: DNT cell can
      significantly inhibit the growth of pancreatic carcinoma in vivo, and the
      mechanism may be involved in abnormal expressions of MICA and NKG2D.

PMID- 28441860
TI  - Smart Luminescent Coordination Polymers toward Multimode Logic Gates: Time
      Resolved, Tribochromic and Excitation-Dependent Fluorescence/Phosphorescence
      Emission.
AB  - In this work, we propose that lanthanide cations (such as Eu3+ and Tb3+)-doped
      long-afterglow coordination polymers (CPs) can be an effective tool for designing
      multimode optical logic gates based on their tunable fluorescence/phosphorescence
      transformation and state-dependent emission. First, multicolor and white-light
      luminescence across the blue/green/yellow/red visible regions can be obtained by
      balancing the co-doping ratio of Eu3+/Tb3+ cations and suitable excitations.
      Additionally, a new tribochromic Eu-Cd-CP was developed based on the mechanism of
      a change in structural symmetry. Benefitting from long-afterglow, tribochromism,
      and excitation-dependent emission on the same luminescent CP, a new three-input
      and three-output logic gate was obtained. Therefore, this work not only provides
      detailed insights into the interesting fields of tribochromism and tunable
      photoemission, but also confirms that long-afterglow CPs can serve as a new
      platform for the construction of smart luminescent systems and multimode optical
      logic gates.

PMID- 28441862
TI  - Spatial-Temporal Dispersion of Aerosolized Nanoparticles During the Use of
      Consumer Spray Products and Estimates of Inhalation Exposure.
AB  - We evaluated the spatial-temporal dispersion of airborne nanomaterials during the
      use of spray consumer products and estimated the level of consumer inhalation
      exposure. A total of eight spray products including five propellant and three
      pump types were selected to evaluate the dispersion of airborne nanoparticles
      across time and space in a cleanroom which could control the background
      particles. Four products were advertised to contain silver and one contained
      titanium nanoparticles, while three products were specified no ENM but as being
      manufactured through the use of nanotechnology. We used direct-reading
      instruments with a thermodesorber unit to measure the particles (number, mass,
      surface area), as well as filter sampling to examine physicochemical
      characteristics. Sampling was conducted simultaneously at each location (1 m,
      near-field; 2, 3 m, far-field) by distance from the source. We estimated the
      inhaled doses at the breathing zone, and the doses deposited in each part of the
      respiratory tract using the experimental data and mathematical models.
      Nanoparticles released from the propellant sprays persisted in the air and
      dispersed over a large distance due to their small size (1466-5565
      particles/cm3). Conversely, the pump sprays produced larger droplets that settled
      out of the air relatively close to the source, so the concentration was similar
      to background level (<200 particles/cm3). The estimates of inhalation exposure
      also suggested that exposure to nanoparticles was greater with propellant sprays
      (1.2 * 108 +/- 4.0 * 107 particles/kgbw/day) than pump sprays (2.7 * 107 +/- 6.5
      * 106 particles/kgbw/day). We concluded that the propellant sprays create a
      higher risk of exposure than the pump sprays.

PMID- 28441861
TI  - Anionic Polymer and Quantum Dot Excipients to Facilitate siRNA Release and Self
      Reporting of Disassembly in Stimuli-Responsive Nanocarrier Formulations.
AB  - The incorporation of anionic excipients into polyplexes is a promising strategy
      for modulating siRNA binding versus release and integrating diagnostic
      capabilities; however, specific design criteria and structure-function
      relationships are needed to facilitate the development of nanocarrier-based
      theranostics. Herein, we incorporated poly(acrylic acid) (PAA) and quantum dot
      (QD) excipients into photolabile siRNA polyplexes to increase gene silencing
      efficiencies by up to 100% and enable self-reporting of nanocarrier disassembly.
      Our systematic approach identified the functional relationships between gene
      silencing and key parameters such as excipient loading fractions and molecular
      weights that facilitated the establishment of design rules for optimization of
      nanocarrier efficacy. For example, we found that PAA molecular weights ~10-20*
      greater than that of the coencapsulated siRNA exhibited the most efficient
      release and silencing. Furthermore, siRNA release assays and RNAi modeling
      allowed us to generate a PAA "heat map" that predicted gene silencing a priori as
      a function of PAA molecular weight and loading fraction. QDs further promoted
      selective siRNA release and provided visual as well as Forster resonance energy
      transfer (FRET)-based monitoring of the dynamic changes in nanostructure in situ.
      Moreover, even with the addition of anionic components, our formulations
      exhibited substantially improved stability and shelf life relative to typical
      formulations, with complete stability after a week of storage and full activity
      in the presence of serum. Taken together, this study enabled synergistic
      improvements in siRNA release and diagnostic capabilities, along with the
      development of mechanistic insights that are critical for advancing the
      translation of nucleic acid theranostics into the clinic.

PMID- 28441863
TI  - High Triplet Energy Level Achieved by Tuning the Arrangement of Building Blocks
      in Phosphorescent Polymer Backbones for Furnishing High Electroluminescent
      Performances in Both Blue and White Organic Light-Emitting Devices.
AB  - A high triplet energy level (ET) of ca. 2.83 eV has been achieved in a novel
      polymer backbone through tuning the arrangement of two kinds of building blocks,
      showing enhanced hole injection/transporting capacity. Based on this new polymer
      backbone with high ET, both blue and white phosphorescent polymers were
      successfully developed with a trade-off between high ET and enhanced charge
      carrier transporting ability. In addition, their photophysical features,
      electrochemical behaviors, and electroluminescent (EL) properties have been
      characterized in detail. Benefitting from the advantages associated with the
      novel polymer backbone, the blue phosphorescent polymers show top-ranking EL
      performances with a maximum luminance efficiency (etaL) of 15.22 cd A-1,
      corresponding to a power efficiency (etaP) of 12.64 lm W-1, and external quantum
      efficiency (etaext) of 6.22% and the stable Commission Internationale de
      L'Eclairage (CIE) coordinates of (0.19, 0.38). Furthermore, blue-orange (B-O)
      complementary-colored white phosphorescent polymers based on this novel polymer
      backbone were also obtained showing encouraging EL efficiencies of 12.34 cd A-1,
      9.59 lm W-1, and 4.10% in the optimized WOLED together with exceptionally stable
      CIE coordinates of (Deltax = 0.014, Deltay = 0.010) in a wide driving voltage
      range from 4 to 16 V. All of these attractive EL results achieved by these novel
      phosphorescent polymers show the great potential of this new polymer backbone in
      developing highly efficient phosphorescent polymers.

PMID- 28441864
TI  - Interfacial Dynamics within an Organic Chromophore-Based Water Oxidation
      Molecular Assembly.
AB  - Photoinduced electron injection, intra-assembly electron transfer, and back
      electron transfer are investigated in a single-site molecular assembly formed by
      covalently linking a phosphonated terthiophene (T3) chromophore to a
      Ru(terpyridine)(bipyridine)(L)2+ (L = MeCN or H2O) water oxidation catalyst
      adsorbed onto a mesoporous metal-oxide (MOx) film. Density functional theory
      calculations of the T3-trpy-Ru-L assembly indicate that the molecular components
      are strongly coupled with enhanced low-energy absorptions owing to the presence
      of an intraligand charge transfer (ILCT) transition between the T3 and trpy
      moieties. Ultrafast spectroscopy of the MOx//T3-trpy-Ru-L assemblies reveals that
      excitation of the surface-bound T3 chromophore results in ps-ns electron
      injection into the metal-oxide conduction band. Electron injection is followed by
      rapid (<35 ps) intra-assembly electron transfer from the RuII catalyst to
      regenerate the T3 chromophore with subsequent back-electron transfer on the
      microsecond time scale.

PMID- 28441865
TI  - Unexpected Effects of K+ and Adenosine Triphosphate on the Thermal Stability of
      Na+,K+-ATPase.
AB  - Na+,K+-ATPase is an integral membrane protein which couples ATP hydrolysis to the
      transport of three Na+ out and two K+ into the cell. The aim of this work is to
      characterize the effect of K+, ATP, and Mg2+ (essential activator) on the Na+,K+
      ATPase thermal stability. Under all conditions tested, thermal inactivation of
      the enzyme is concomitant with a structural change involving the ATP binding site
      and membrane-associated regions. Both ligands exert a clear stabilizing effect
      due to both enthalpic and entropic contributions. Competition experiments between
      ATP and K+ showed that, when ATP is present, the inactivation rate coefficient
      exhibits a biphasic dependence on K+ concentration. At low [K+], destabilization
      of the enzyme is observed, while stabilization occurred at larger cation
      concentrations. This is not expected for a simple competition between the enzyme
      and two ligands that individually protect the enzyme. A model that includes
      enzyme species with none, one, or two K+ and/or one molecule of ATP bound
      explains the experimental data. We concluded that, despite both ligands
      stabilizing the enzyme, the species with one K+ and one ATP simultaneously bound
      is unstable.

PMID- 28441866
TI  - Interactions of Insoluble Residue from Enzymatic Hydrolysis of Brewer's Spent
      Grain with Intestinal Microbiota in Mice.
AB  - Brewer's spent grain (BSG) is the major side-stream from brewing. As BSG is rich
      in dietary fiber and protein, it could be used in more valuable applications,
      such as nutritional additives for foods. Our aim was to elucidate whether an
      insoluble lignin-rich fraction (INS) from BSG is metabolized by mice gut
      microbiota and how it affects the microbiota. Our results indicated that lignin
      was partially degraded by the gut microbiota, degradation products were absorbed,
      and finally excreted in urine. Therefore, they contribute to the phenolic pool
      circulating in the mammalian body, and may have systemic effects on health. In
      addition, the effects of the test diets on the microbiota were significant. Most
      interestingly, diversities of predominant cecal and fecal bacteria were higher
      after the intervention diet containing INS than after the intervention diet
      containing cellulose. Since low fecal bacterial diversity has been linked with
      numerous diseases and disorders, the diversity increasing ability opens very
      interesting perspectives for the future.

PMID- 28441867
TI  - Accurate Neural Network Description of Surface Phonons in Reactive Gas-Surface
      Dynamics: N2 + Ru(0001).
AB  - Ab initio molecular dynamics (AIMD) simulations enable the accurate description
      of reactive molecule-surface scattering especially if energy transfer involving
      surface phonons is important. However, presently, the computational expense of
      AIMD rules out its application to systems where reaction probabilities are
      smaller than about 1%. Here we show that this problem can be overcome by a high
      dimensional neural network fit of the molecule-surface interaction potential,
      which also incorporates the dependence on phonons by taking into account all
      degrees of freedom of the surface explicitly. As shown for N2 + Ru(0001), which
      is a prototypical case for highly activated dissociative chemisorption, the
      method allows an accurate description of the coupling of molecular and surface
      atom motion and accurately accounts for vibrational properties of the employed
      slab model of Ru(0001). The neural network potential allows reaction
      probabilities as low as 10-5 to be computed, showing good agreement with
      experimental results.

PMID- 28441868
TI  - Spectral Contributions to the Thermal Conductivity of C60 and the Fullerene
      Derivative PCBM.
AB  - We investigate the heat transport mechanisms responsible in driving the
      characteristic temperature-dependent thermal conductivities of C60 and PCBM
      crystals via molecular dynamics simulations. We find that the thermal
      conductivity of PCBM is "ultralow" across the temperature range studied in this
      work. In contrast, the temperature-dependent thermal conductivity of C60 crystals
      exhibits two regimes: "crystal-like" behavior at low temperatures where thermal
      conductivity increases rapidly with decreasing temperature and temperature
      independent thermal conductivities at higher temperatures. The spectral
      contributions to thermal conductivity for C60 suggest that the majority of heat
      is carried by modes in the low-frequency regime (<2 THz), which is a consequence
      of intermolecular interactions. Unlike for C60, these modes are not responsible
      for heat conduction in PCBM due to the mismatch in density of states introduced
      by the addition of low-frequency modes from the alkyl chains that are attached to
      the fullerene moieties.

PMID- 28441869
TI  - Highly Transparent, Conductive, and Bendable Ag Nanowire Electrodes with Enhanced
      Mechanical Stability Based on Polyelectrolyte Adhesive Layer.
AB  - In this paper, a highly transparent, conductive, and bendable Ag nanowire (AgNW)
      based electrode with excellent mechanical stability was prepared through the
      introduction of an adhesive polyelectrolyte multilayer between AgNW networks and
      a polyethylene terephthalate (PET) substrate. The introduction of the adhesive
      layer was performed based on a peel-assembly-transfer procedure, and the adhesive
      polyelectrolyte greatly improved the mechanical stability of the AgNW transparent
      conductive films (TCFs) without obviously attenuating the morphology and
      optoelectrical properties of the AgNW networks. The as-prepared AgNW TCFs
      simultaneously possess high optical transparency, good conductivity, excellent
      flexibility, and remarkable mechanical stability. It is believed that the
      proposed strategy would pave a new way for preparing flexible transparent
      electrodes with a long-term stability, which is significant in the development
      and practical applications of flexible transparent electronic devices operated in
      severe environments.

PMID- 28441870
TI  - Protein-Nanocellulose Interactions in Paper Filters for Advanced Separation
      Applications.
AB  - Protein-based pharmaceutics are widely explored for healthcare applications, and
      6 out of 10 best-selling drugs today are biologicals. The goal of this work was
      to evaluate the protein nanocellulose interactions in paper filter for advanced
      separation applications such as virus removal filtration and bioprocessing. The
      protein recovery was measured for bovine serum albumin (BSA), gamma-globulin, and
      lysozyme using biuret total protein reagent and polyacrylamide gel
      electrophoresis (PAGE), and the throughput was characterized in terms of flux
      values from fixed volume filtrations at various protein concentrations and under
      worst-case experimental conditions. The affinity of cellulose to bind various
      proteins, such as BSA, lysozyme, gamma-globulin, and human IgG was quantified
      using a quartz crystal microbalance (QCMB) by developing a new method of fixing
      the cellulose fibers to the electrode surface without cellulose dissolution
      precipitation. It was shown that the mille-feuille filter exhibits high protein
      recovery, that is, ~99% for both BSA and lysozyme. However, gamma-globulin does
      not pass through the membrane due to its large size (i.e., >180 kDa). The PAGE
      data show no substantial change in the amount of dimers and trimers before and
      after filtration. QCMB analysis suggests a low affinity between the nanocellulose
      surface and proteins. The nanocellulose-based filter exhibits desirable inertness
      as a filtering material intended for protein purification.

PMID- 28441871
TI  - Frequency-Dependent Solvent Impedance and Colloid Microelectrophoresis
      Measurements in Partially Polar Solvents.
AB  - We carry out frequency-dependent solvent impedance measurements and alternating
      current (ac) colloid microelectrophoresis experiments in partially polar solvents
      in the low-frequency regime (0.25 Hz <= f <= 10 Hz). Solvent electrode
      polarization effects are quantified first in partially polar solvent mixtures
      containing bromocyclohexane (CHB). We find that the polarization capacitance from
      electrode polarization exhibits a clear power law behavior Cp = Cp0 f-m with
      power law exponent m = 0.25 +/- 0.04. Once we account for electrode polarization
      effects, we are able to obtain quantitative mobilities in the low-frequency
      regime from our ac microelectrophoresis measurements; for these measurements, we
      use poly(methyl methacrylate colloids that are gravitationally confined to a
      plane while suspended in a low-polar solvent mixture of cis-trans
      decahydronapthalene and CHB. We find that the dimensionless electrophoretic
      mobility is constant, consistent with expectations for frequencies below the ion
      diffusion frequency, and has a value E = 1.6 +/- 0.4.

PMID- 28441872
TI  - Unraveling the Nature of Anomalously Fast Energy Storage in T-Nb2O5.
AB  - While T-Nb2O5 has been frequently reported to display an exceptionally fast rate
      of Li-ion storage (similar to a capacitor), the detailed mechanism of the energy
      storage process is yet to be unraveled. Here we report our findings in probing
      the nature of the ultrafast Li-ion storage in T-Nb2O5 using both experimental and
      computational approaches. Experimentally, we used in operando Raman spectroscopy
      performed on a well-designed model cell to systematically characterize the
      dynamic evolution of vibrational band groups of T-Nb2O5 upon insertion and
      extraction of Li ions during repeated cycling. Theoretically, our model shows
      that Li ions are located at the loosely packed 4g atomic layers and prefer to
      form bridging coordination with the oxygens in the densely packed 4h atomic
      layers. The atomic arrangement of T-Nb2O5 determines the unique Li-ion diffusion
      path topologies, which allow direct Li-ion transport between bridging sites with
      very low steric hindrance. The proposed model was validated by computational and
      experimental vibrational analyses. A comprehensive comparison between T-Nb2O5 and
      other important intercalation-type Li-ion battery materials reveals the key
      structural features that lead to the exceptionally fast kinetics of T-Nb2O5 and
      the cruciality of atomic arrangements for designing a new generation of Li-ion
      conduction and storage materials.

PMID- 28441873
TI  - Identification and Characterization of a Secondary Sodium-Binding Site and the
      Main Selectivity Determinants in the Human Concentrative Nucleoside Transporter
      3.
AB  - The family of concentrative Na+/nucleoside cotransporters in humans is
      constituted by three subtypes, namely, hCNT1, hCNT2, and hCNT3. Besides their
      different nucleoside selectivity, hCNT1 and hCNT2 have a Na+/nucleoside
      stoichiometry of 1:1, while for hCNT3 it is 2:1. This distinct stoichiometry of
      subtype 3 might hint the existence of a secondary sodium-binding site that is not
      present in the other two subtypes, but to date their three-dimensional structures
      remain unknown and the residues implicated in Na+ binding are unclear. In this
      work, we have identified and characterized the Na+ binding sites of hCNT3 by
      combining molecular modeling and mutagenesis studies. A model of the transporter
      was obtained by homology modeling, and key residues of two sodium-binding sites
      were identified and verified with a mutagenesis strategy. The structural model
      explains the altered sodium-binding properties of the hCNT3C602R polymorphic
      variant and supports previously generated data identifying the determinant
      residues of nucleoside selectivity, paving the way to understand how drugs can
      target this plasma membrane transporter.

PMID- 28441875
TI  - Introduction: Unusual Enzymology in Natural Product Synthesis.

PMID- 28441877
TI  - Health justice partnerships: initial insights into the delivery of an integrated
      health and legal service for youth in regional Victoria.
AB  - INTRODUCTION: This article presents interim findings from research examining the
      implementation of a health justice partnership (HJP) focusing on the legal and
      health needs of regional young people. HJPs provide an innovative service model
      offering an integrated health and legal service for the community. HJPs are a
      relatively new service model for Australia, yet the program is well suited to
      meet the needs of particular population cohorts, including young people and those
      in regional locations experiencing complex legal issues. METHODS: Funded by the
      Victorian Legal Services Board and Commissioner, an HJP in partnership with three
      organisations was established in a large regional area in Victoria, Australia.
      Research is being conducted alongside the program to examine its impact on young
      people, and the implications on practice for staff in the partner organisations.
      RESULTS: Findings provide preliminary support for the HJP model with a number of
      young people - from predominantly disadvantaged backgrounds and with varying
      legal issues - having been referred to the program in the first 6 months.
      Referrals were received from both partner agencies and external agencies. Initial
      client and staff survey responses indicate that the legal problem of the young
      people was affecting how they feel. CONCLUSIONS: While these findings provide
      preliminary support for the HJP further research will offer longer term insights
      about HJPs within the Australian context, particularly rural and regional
      settings.

PMID- 28441878
TI  - Four new anthraquinones from a soil actinomycete Streptomyces sp. WS-13394 and
      their bioactivities.
AB  - Further chemical study of secondary metabolites from the soil actinomycete
      Streptomyces sp. WS-13394 resulted in the isolation of four new alkylated
      anthraquinone analogues (5-8). Their structures were elucidated on the basis of
      extensive spectroscopic analysis, including HR-ESI-MS, 1D and 2D NMR. The new
      compounds, together with analogues obtained before (1-4), were tested for their
      in vitro cytotoxicity against Huh-7 and SGC-7901.

PMID- 28441874
TI  - Natural [4 + 2]-Cyclases.
AB  - [4 + 2]-Cycloadditions are increasingly being recognized in the biosynthetic
      pathways of many structurally complex natural products. A relatively small
      collection of enzymes from these pathways have been demonstrated to increase
      rates of cyclization and impose stereochemical constraints on the reactions.
      While mechanistic investigation of these enzymes is just beginning, recent
      studies have provided new insights with implications for understanding their
      biosynthetic roles, mechanisms of catalysis, and evolutionary origin.

PMID- 28441879
TI  - Willingness to Invest in Children: Psychological Kinship Estimates and Emotional
      Closeness.
AB  - In general, adults invest more in related children compared to unrelated
      children. To test whether this pattern reflects variations in psychological
      kinship estimates (i.e., putative relatedness weighted by certainty in
      relatedness), willingness to invest in children belonging to different categories
      (direct offspring, nieces/nephews, stepchildren, and friends' children) was
      measured in a population-based sample of 1,012 adults. Respondents reported more
      willingness to invest in their own biological children, than in other related
      children (nieces and nephews), or in stepchildren and friends' children. Compared
      to putative relatedness, respondents' psychological kinship estimates better
      predicted the willingness to invest. This association was partially mediated by
      emotional closeness. Additionally, the age of a child and the number of children
      in the care of the respondent were negatively associated with willingness to
      invest. The association between psychological kinship estimates and willingness
      to invest supports evolutionary predictions. Investment in stepchildren was,
      however, higher than expected.

PMID- 28441880
TI  - A three-dimensional collagen-fiber network model of the extracellular matrix for
      the simulation of the mechanical behaviors and micro structures.
AB  - The extracellular matrix (ECM) provides structural and biochemical support to
      cells and tissues, which is a critical factor for modulating cell dynamic
      behavior and intercellular communication. In order to further understand the
      mechanisms of the interactive relationship between cell and the ECM, we developed
      a three-dimensional (3D) collagen-fiber network model to simulate the micro
      structure and mechanical behaviors of the ECM and studied the stress-strain
      relationship as well as the deformation of the ECM under tension. In the model,
      the collagen-fiber network consists of abundant random distributed collagen
      fibers and some crosslinks, in which each fiber is modeled as an elastic beam and
      a crosslink is modeled as a linear spring with tensile limit, it means crosslinks
      will fail while the tensile forces exceed the limit of spring. With the given
      parameters of the beam and the spring, the simulated tensile stress-strain
      relation of the ECM highly matches the experimental results including damaged and
      failed behaviors. Moreover, by applying the maximal inscribed sphere method, we
      measured the size distribution of pores in the fiber network and learned the
      variation of the distribution with deformation. We also defined the alignment of
      the collagen-fibers to depict the orientation of fibers in the ECM
      quantitatively. By the study of changes of the alignment and the damaged
      crosslinks against the tensile strain, this paper reveals the comprehensive
      mechanisms of four stages of 'toe', 'linear', 'damage' and 'failure' in the
      tensile stress-strain relation of the ECM which can provide further insight in
      the study of cell-ECM interaction.

PMID- 28441881
TI  - Sex Education in Children and Adolescents With Disabilities in Yogyakarta,
      Indonesia From a Teachers' Gender Perspective.
AB  - Children and adolescents with disabilities (CAD) frequently engage in
      inappropriate sexual behaviors. In Indonesia, the need for sex education for CAD
      remains unclear. This study investigated teacher attitudes toward providing sex
      education in special schools to clarify the gender differences among teachers
      providing sex education. Questionnaires were sent to 180 teachers. The response
      rate was 72.2%. Eighty-three percent of responders were Muslim. Our findings
      revealed that teachers in special schools considered sex education to be
      important. However, the number of sex education contents was limited, and female
      teachers were more positive about teaching sex education than male teachers.
      Equally, female teachers taught a greater number of sex education contents than
      did male teachers. These findings were consistent with reports from developed
      countries although cultural and religious background differed from those of
      Indonesia. Sex education for CAD was accepted by teachers in Indonesia; however,
      materials and tools for education should be developed further.

PMID- 28441882
TI  - Work right to right work: An automythology of chronic illness and work.
AB  - Objectives Chronic illness is known to disrupt and redirect the usual course of
      work trajectories. This article aims to portray the longitudinal course of
      negotiating work after multiple sclerosis. Methods Using therapy and personal
      journals to reconstruct memories and experience, an autoethnography is produced
      and narrated within Campbell's "Hero's Journey" automythology framework. Results
      The narrative highlights the intrasubjectivity of illness meaning-the changing
      internal meaning-making and external behavior and decision-making dynamics. The
      journey of being inhibited to "Work Right", to "Looking for the Right" and
      ultimately, finding "Right Work" is charted; portrayed as a bittersweet maneuver
      to achieve work-illness equilibrium. Discussion This journey traverses a spectrum
      of negative coping-the exhibition of deviant work behaviors, disengagement and
      depression; to recalibration and renewal; culminating in living the "new normal",
      and finding moral and meaningful work engagements. Life trajectories with chronic
      illness are often skewed and redirected; but longitudinal narratives of
      normalization and coping also highlight the pursuits to secure and maintain a
      life of meaning and value.

PMID- 28441883
TI  - Chemical constituents from Gueldenstaedtia verna and their anti-inflammatory
      activity.
AB  - A new triterpenoid glycoside (1) and 15 known compounds (2-16) were isolated from
      the whole plants of Gueldenstaedtia verna. The new compound (1) was identified as
      complogenin 22-O-beta-d-glucopyranoside by extensive spectroscopic techniques
      including 1D (1H and 13C) and 2D NMR experiments (HSQC, HMBC and NOESY), HR-DART
      MS and chemical methods. Most of the isolates were evaluated for their inhibitory
      activities on LPS-induced NO production in RAW 264.7 cells. The inhibitory
      effects of the active compounds, sulphuretin (8) and (22E,24S)-5alpha,8alpha
      epidioxy-24-methyl-cholesta-6,9(11),22-trien-3beta-ol (13), on the production of
      pro-inflammatory mediators (including IL-6, IL1beta and PGE2) were further
      estimated in vitro by ELISA in RAW 264.7 macrophages.

PMID- 28441885
TI  - Lactobacillus plantarum L9 but not Lactobacillus acidophilus LA reduces tumour
      necrosis factor induced bacterial translocation in Caco-2 cells.
AB  - Translocation of bacteria across the intestinal barrier is important in the
      pathogenesis of systemic sepsis and multiple organ dysfunction syndromes.
      Inflammatory cytokines increase paracellular permeability that allows increased
      luminal bacteria to translocate across mucosal epithelium and further deteriorate
      the gut barrier. In order to reduce this risk, the prophylactic use of probiotics
      has been recently addressed. In this paper, we investigate the protective role
      toward tumour necrosis factor (TNF)-alpha induced non-pathogenic Escherichia coli
      translocation across Caco-2 monolayers of Lactobacillus strains. According to our
      experimental data, Lactobacillus plantarum L9 and Lactobacillus acidophilus LA
      have good capacities to adhere to Caco-2 cells. Addition of L. plantarum L9 and
      L. acidophilus LA to the enterocyte monolayer surface result in significant
      inhibition of E. coli adhesion and cell internalisation. However, L. plantarum L9
      and L. acidophilus LA did not inhibit the growth of the non-pathogenic E. coli B5
      after 24 h incubation. Exposure to TNF-alpha for 6 h caused a dramatic increase
      in E. coli B5 translocation across Caco-2 cells, which was uncoupled from
      increases in paracellular permeability. Pretreatment with L. plantarum L9 prevent
      TNF-alpha induced transcellular bacterial translocation and IL-8 production in
      Caco-2 cells. L. plantarum L9 also did not affect the integrity of the
      monolayers, as indicated by lactate dehydrogenase release, horseradish peroxidase
      permeability, and transepithelial electrical resistance. L. plantarum L9 showed
      the potential to protect enterocytes from an acute inflammatory response and
      therefore could be good potential prophylactic agents in counteracting bacterial
      translocation.

PMID- 28441886
TI  - Differences between live and heat-killed bifidobacteria in the regulation of
      immune function and the intestinal environment.
AB  - Probiotics are live microorganisms that confer a health benefit on the host, such
      as improvement of the intestinal environment, modulation of immune function and
      energy metabolism. Heat-killed probiotic strains have also been known to exhibit
      some physiological functions; however, the differences between live and heat
      killed probiotics have not been well elucidated. In this study, we investigated
      the differences between live and heat-killed Bifidobacterium breve M-16V, a
      probiotic strain, in the regulation of immune function, intestinal metabolism and
      intestinal gene expression of the host using gnotobiotic mouse model and omics
      approaches. Both live and heat-killed cells of B. breve M-16V showed immune
      modulating effects that suppressed pro-inflammatory cytokine production in spleen
      cells and affected intestinal metabolism; however, live cells exhibited a more
      remarkable effect in the regulation of intestinal metabolism and intestinal gene
      expression involved in nutrient metabolism. Our findings are valuable for
      considering the health benefits of live and heat-killed bacteria and the
      usefulness of different forms of probiotics.

PMID- 28441884
TI  - Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from
      neurophysiology to neuroimaging.
AB  - Patients with schizophrenia self-administer nicotine at rates higher than is self
      administered for any other psychiatric illness. Although the reasons are unclear,
      one hypothesis suggests that nicotine is a form of 'self-medication' in order to
      restore normal levels of nicotinic signaling and target abnormalities in neuronal
      function associated with cognitive processes. This brief review discusses
      evidence from neurophysiological and neuroimaging studies in schizophrenia
      patients that nicotinic agonists may effectively target dysfunctional neuronal
      circuits in the illness. Evidence suggests that nicotine significantly modulates
      a number of these circuits, although relatively few studies have used modern
      neuroimaging techniques (e.g. functional magnetic resonance imaging (fMRI)) to
      examine the effects of nicotinic drugs on disease-related neurobiology. The
      neuronal effects of nicotine and other nicotinic agonists in schizophrenia remain
      a priority for psychiatry research.

PMID- 28441887
TI  - Chemical constituents and biological activities from branches of Colubrina
      asiatica.
AB  - Sixteen compounds were isolated from a Thai medicinal plant, Colubrina asiatica.
      The isolated compounds were elucidated on the basis of spectroscopic methods (IR,
      1D and 2D NMR) as six triterpene acids (1-6), five steroids (7-11), one benzoic
      acid derivative (12), two peptides (13 and 14), one sesquiterpenoid (15) and one
      jujubogenin (16). Compounds 3 and 10 showed antimalarial activity against
      Plasmodium falciparum. Compound 5 showed antimycobacterial activity. Moreover,
      compounds 3, 5, 6, 10 and 14 exhibited weak cytotoxicity against cancer cell
      lines. Compounds 1-15 have been isolated for the first time from this plant.

PMID- 28441888
TI  - Doxorubicin-induced female reproductive toxicity: an assessment of ovarian
      follicular apoptosis, cyclicity and reproductive tissue histology in Wistar rats.
AB  - Doxorubicin is a widely used chemotherapeutic agent for various cancers,
      particularly for the female breast cancer patients. Although the rate of young
      female cancer patients is increasing every year, conversely the lack of knowledge
      of adverse effects of doxorubicin on female reproductive system insisted us to
      assess the toxic effects of doxorubicin on the female reproductive tissue
      histoarchitecture, cyclicity, and mammary glands in Wistar rats. The rats were
      divided into two groups depending on the treatment period, i.e., 24 h and 28 d
      and further subdivided into three subgroups and administered with doxorubicin at
      3 mg/kg bw (subgroup I), 6 mg/kg bw (subgroup II), and equal volume of normal
      saline (subgroup III) intraperitoneally once during the whole treatment period.
      We observed a significantly altered estrous cycle with a prolonged diestrous and
      short proestrous in higher dose group and dose-dependent significant changes in
      the uteri and mammary gland histoarchitecture in 28 days treated rats as compared
      to control. Moreover, the micronuclei and chromosomal aberration frequency were
      increased significantly in both treatment groups. A significant increase in
      follicular atresia in ovaries of the 28 days treated rats was observed. The
      immunohistochemical analysis of ovarian tissues showed an increased p53 and
      caspase 3 expression and apoptosis in primordial follicles of treated rats. The
      results suggest that though doxorubicin is a potential chemotherapeutic drug for
      many tumors, but the risk of adverse effects on the female reproductive system is
      there even at low doses.

PMID- 28441889
TI  - Insight on the impacts of free amino acids and their metabolites on the immune
      system from a perspective of inborn errors of amino acid metabolism.
AB  - INTRODUCTION: Amino acids (AAs) support a broad range of functions in living
      organisms, including several that affect the immune system. The functions of the
      immune system are affected when free AAs are depleted or in excess because of
      external factors, such as starvation, or because of genetic factors, such as
      inborn errors of metabolism. Areas covered: In this review, we discuss the
      current insights into how free AAs affect immune responses. When possible, we
      make comparisons to known disease states resulting from inborn errors of
      metabolism, in which changed levels of AAs or AA metabolites provide insight into
      the impact of AAs on the human immune system in vivo. We also explore the
      literature describing how changes in AA levels might provide pharmaceutical
      targets for safe immunomodulatory treatment. Expert opinion: The impact of free
      AAs on the immune system is a neglected topic in most immunology textbooks. That
      neglect is undeserved, because free AAs have both direct and indirect effects on
      the immune system. Consistent choices of pre-clinical models and better
      strategies for creating formulations are required to gain clinical impact.

PMID- 28441890
TI  - Rosuvastatin ameliorates cognitive impairment in rats fed with high-salt and
      cholesterol diet via inhibiting acetylcholinesterase activity and amyloid beta
      peptide aggregation.
AB  - Amyloid beta (Abeta) peptide aggregation and cholinergic neurodegeneration are
      involved in the development of cognitive impairment. Therefore, in this article,
      we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its
      potential as a dual inhibitor of acetylcholinesterase (AChE) and Abeta peptide
      aggregation for the treatment of cognitive impairment. Molecular docking study
      was done to examine the affinity of RSV with Abeta1-42 and AChE in silico. We
      also employed neurobehavioral activity tests, biochemical estimation, and
      histopathology to study the anti-Abeta1-42 aggregation capability of RSV in vivo.
      Molecular docking study provided evidence that RSV has the best binding conformer
      at its receptor site or active site of an enzyme. The cognitive impairment in
      female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad
      libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and
      Abeta1-42 peptide aggregations in HSCD induced cognitive impairment. In addition,
      RSV-treated rats showed greater scores in the open field (locomotor activity)
      test. Moreover, the histopathological studies in the hippocampus and cortex of
      rat brain also supported that RSV markedly reduced the cognitive impairment and
      preserved the normal histoarchitectural pattern of the hippocampus and cortex.
      Taken together, these data indicate that RSV may act as a dual inhibitor of AChE
      and Abeta1-42 peptide aggregation, therefore suggesting a therapeutic strategy
      for cognitive impairment treatment.

PMID- 28441891
TI  - Investigational and experimental GnRH analogs and associated neurotransmitters.
AB  - INTRODUCTION: The GnRH agonistic analogs enable for desensitizing the hypothalamo
      pituitary-gonadal axis in malignant and benign conditions where minimizing the
      production of sex hormones, or blocking ovulation is necessary. The possible
      indications are prostate cancer, benign prostate hyperplasia, breast cancer,
      endometriosis, precocious puberty, uterine leiomyomata, assisted reproduction
      (ART)/in vitro fertilization (IVF), PCOS, minimizing the gonadotoxic effect of
      chemotherapy in young women, and possibly ovarian cancer. Areas covered: The aim
      of the current review is to summarize, giving a critical overview, of the
      investigational GnRH agonists, and shortly discuss the difference between the
      GnRH agonists, antagonists, Kisspeptin, and Neurokinin B analogs. Expert opinion:
      The broad armamentarium of agonists may make it possible, in the future, to
      expand the indications and uses of these analogs, choosing and specifically
      tailoring the analog to the required effect, while minimizing side effects.

PMID- 28441893
TI  - Evaluation of health information systems research in information systems
      research: A meta-analysis.
AB  - Given the importance of the health-care industry and the promise of health
      information systems, researchers are encouraged to build on the shoulders of
      giants as the saying goes. The health information systems field has a unique
      opportunity to learn from and extend the work that has already been done by the
      highly correlated information systems field. As a result, this research article
      presents a past, present and future meta-analysis of health information systems
      research in information systems journals over the 2000-2015 time period. Our
      analysis reviewed 126 articles on a variety of topics related to health
      information systems research published in the "Senior Scholars" list of the top
      eight ranked information systems academic journals. Across the selected
      information systems academic journals, our findings compare research
      methodologies applied, health information systems topic areas investigated and
      research trends. Interesting results emerge in the range and evolution of health
      information systems research and opportunities for health information systems
      researchers and practitioners to consider moving forward.

PMID- 28441892
TI  - Changes in blood and urinary cadmium levels and bone mineral density according to
      osteoporosis medication in individuals with an increased cadmium body burden.
AB  - The aim of this study was to assess changes in bone mineral density (BMD) and
      cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated
      area according to the type of osteoporosis medication over a three-year period.
      This follow-up study included 204 residents living in the vicinity of a closed
      copper refinery, who had been found to have elevated urinary or blood Cd levels.
      Cd levels in the blood and urine, as well as BMD, were measured every 6 months.
      After the first BMD measurement, individuals were prescribed antiresorptives such
      as alendronate or vitamin D and calcium, according to their BMD. Subjects were
      classified according to the type of medicine provided over the previous 6 months.
      General linear models controlling for other factors were used to evaluate the
      effects of each type of medication on the participants' Cd levels and BMD. Spinal
      BMD showed a significant increase in the antiresorptive group compared to the
      nontreatment group. Significant decreases in blood Cd levels were found in the
      vitamin D and calcium group, in comparison to the nontreatment group, as well as
      a marginally significant decrease in the antiresorptive group. The vitamin D and
      calcium group showed a significantly greater decrease in urinary Cd levels than
      the nontreatment group. In contrast, antiresorptive medication was found to have
      a negative effect on urinary Cd excretion. These results suggest that vitamin D
      and calcium treatment for osteoporosis lowers blood Cd levels more effectively
      and improves urinary Cd excretion.

PMID- 28441894
TI  - Self-directed exercise in multiple sclerosis: Evaluation of a home automated tele
      management system.
AB  - Introduction Physical rehabilitation is one of the few non-pharmaceutical
      therapies for maintaining or improving walking ability for patients with multiple
      sclerosis. However, travel distance to rehabilitation clinics, neurological
      disability and insurance coverage often limit access to specialised
      rehabilitation services. To address these issues, we utilised a web-based system
      to support a home-based self-directed exercise programme. Methods Patients ( n =
      24) were randomised to either routine home rehabilitation or to the multiple
      sclerosis home automated tele-management system for a six-month period. The study
      group had a mean age of 50.4 years, 56% of patients were male, and 67% had
      progressive multiple sclerosis with an overall mean Patient Determined Disease
      Steps score of 4.4 (cane or crutch required for walking). Key outcomes included
      the timed 25-foot-walk, six-minute-walk and the Berg Balance Scale. Results There
      was no statistically significant difference in the change of the primary walking
      outcome measure, timed 25-foot-walk, at six months between the home automated
      tele-management intervention and control groups ( p = 0.44). Similarly, change
      scores for the six-minute-walk were not significantly different between the home
      automated tele-management or control groups at six months. Discussion Maintaining
      overall gait abilities in this group of predominantly progressive multiple
      sclerosis patients is notable. Exercise adherence was positively associated with
      higher multiple sclerosis disability and self-reported walking ability. Study
      engagement and participation in routine home-based exercise for the entire study
      period was challenging. Further research using clinical video telerehabilitation
      techniques that optimise patient involvement warrants further study.

PMID- 28441895
TI  - Ketamine's dose-related effects on anxiety symptoms in patients with treatment
      refractory anxiety disorders.
AB  - The N-methyl-D-aspartate receptor antagonist ketamine has rapid onset activity in
      treatment-resistant depression, post-traumatic stress disorder and obsessive
      compulsive disorder. Due to similarities in brain network activity in depression
      and anxiety disorders, we hypothesized that ketamine might also be active in
      other refractory anxiety disorders. We evaluated the efficacy and safety of
      ketamine in 12 patients with refractory generalized anxiety disorder and/or
      social anxiety disorder who were not currently depressed, using an ascending
      single dose study design (0.25, 0.5, 1 mg/kg administered subcutaneously) at
      weekly intervals. Within 1 h of dosing, patients reported reduced anxiety, which
      persisted for up to seven days. A dose-response profile was noted for anxiolytic
      effects, dissociative side effects, and changes in blood pressure and heart rate,
      with minor changes at 0.25 mg/kg, and progressively greater and more durable
      changes at the higher doses. Ten of 12 patients were treatment responders at 0.5
      1 mg/kg. Ketamine was safe and well tolerated in this population. Ketamine may be
      a potential therapeutic alternative for patients with refractory generalized
      anxiety disorder/social anxiety disorder. Along with its demonstrated
      effectiveness in patients with treatment-resistant depression, obsessive
      compulsive disorder and post-traumatic stress disorder, these data raise the
      intriguing possibility that ketamine may have broad efficacy in disorders
      characterized by negative emotional states, and that these disorders may share a
      common precipitating neurobiology.

PMID- 28441896
TI  - Dissecting the Yale-Brown Obsessive-Compulsive Scale severity scale to understand
      the routes for symptomatic improvement in obsessive-compulsive disorder.
AB  - We aimed to investigate which items of the Yale-Brown Obsessive-Compulsive
      Severity Scale best discriminate the reduction in total scores in obsessive
      compulsive disorder patients after 4 and 12 weeks of pharmacological treatment.
      Data from 112 obsessive-compulsive disorder patients who received fluoxetine (?80
      mg/day) for 12 weeks were included. Improvement indices were built for each Yale
      Brown Obsessive-Compulsive Severity Scale item at two timeframes: from baseline
      to week 4 and from baseline to week 12. Indices for each item were correlated
      with the total scores for obsessions and compulsions and then ranked by
      correlation coefficient. A correlation coefficient ?0.7 was used to identify
      items that contributed significantly to reducing obsessive-compulsive disorder
      severity. At week 4, the distress items reached the threshold of 0.7 for
      improvement on the obsession and compulsion subscales although, contrary to our
      expectations, there was greater improvement in the control items than in the
      distress items. At week 12, there was greater improvement in the time,
      interference, and control items than in the distress items. The use of fluoxetine
      led first to reductions in distress and increases in control over symptoms before
      affecting the time spent on, and interference from, obsessions and compulsions.
      Resistance did not correlate with overall improvement. Understanding the pathway
      of improvement with pharmacological treatment in obsessive-compulsive disorder
      may provide clues about how to optimize the effects of medication.

PMID- 28441897
TI  - Return to work after mild-to-moderate stroke: work satisfaction and predictive
      factors.
AB  - A large proportion of stroke patients are unable to return to work (RTW),
      although figures vary greatly. A total of 121 mild-to-moderate stroke patients,
      who had a paid job at the time of their stroke were included (a) to quantify RTW
      and work satisfaction one-year post-stroke (using the Utrecht Scale for
      Evaluation of Rehabilitation-Participation) and (b) to determine factors
      predicting RTW post-stroke, based on stroke-related, personal and
      neuropsychological variables. Half of the patients were not in work (28%) or were
      working less (22%) than pre-stroke. Ninety percent of those in fulltime
      employment post-stroke were satisfied with their occupational situation, against
      36% of the unemployed participants. In regards to factors predicting RTW, global
      cognitive functioning (r = .19, Montreal Cognitive Assessment) and depressive
      symptoms (r = -.16, Hospital Anxiety and Depression Scale) at two months post
      stroke onset were associated with return to work within one year. Only global
      cognitive functioning was an independent predictor of RTW (11.3% variance, p =
      .013). Although the explained variance was not that high, neuropsychological
      factors probably play a pivotal role in returning to work and should be taken
      into account during rehabilitation after mild and moderate stroke.

PMID- 28441898
TI  - Novel Route of Sirolimus Administration in a Neonate.
AB  - A term newborn presented with widespread cutaneous erythematous to bluish lesions
      since birth. He had extensive lesions in the gastrointestinal tract, brain,
      retina, heart, and bones. He also developed an intestinal perforation due to
      erosion of an intestinal lesion. Due to his critical status and clinical
      presentation, he was initially diagnosed with multifocal
      lymphangioendotheliomatosis with thrombocytopenia (MLT), and sirolimus treatment
      was initiated. Sirolimus was given by buccal route in this nonfeeding patient.
      Therapeutic serum levels were obtained comparable to enteral administration.
      Buccal mucosa was an effective novel route of sirolimus administration in this
      patient.

PMID- 28441899
TI  - Clinical and Financial Outcomes Evaluation of Multimodal Pharmacist Warfarin
      Management of a Statewide Urban and Rural Population.
AB  - PURPOSE: To evaluate the efficacy, safety, and indirect financial outcomes of
      pharmacist face-to-face warfarin management with telephone-based distance
      management utilizing local laboratories or patient self-testing (PST). METHODS: A
      retrospective analysis of a clinic population of 336 patients on established
      warfarin therapy distributed statewide in rural and urban settings over a 6-month
      period was conducted. Participants were stratified into face-to-face management,
      telephone-based management utilizing local laboratory testing, and telephone
      based management utilizing PST. RESULTS: The primary outcome of international
      normalized ratio (INR) time in therapeutic range (TTR) for face-to-face
      management was significantly greater than distance management utilizing local
      laboratory testing (69.0% vs 60.5%, P = .0032). No difference was observed
      between face-to-face management and PST (69.0% vs 68.0%, P = .25). No significant
      difference in bleeding or thromboses was observed. Although increased clinician
      time was utilized during face-to-face encounters compared to telephone encounters
      (8.7-minute face-to-face, 5.5-minute local laboratory, and 5.4-minute PST), face
      to-face encounters tended to be billable at lower levels, whereas telephone-based
      encounters were billable at higher levels. CONCLUSION: A multimodal approach to
      pharmacist warfarin management of a patient population distributed statewide in
      rural and urban locations is effective despite TTR differences associated with
      INR testing used in distance management. PST may improve warfarin treatment
      outcomes and adherence in distance management, particularly when the use of
      alternative oral anticoagulants is inappropriate. Although time and billing
      differences between face-to-face and distance management exist, clinical and
      safety outcomes remain acceptable despite encounter complexity and support
      reimbursement of pharmacist anticoagulation management in all settings.

PMID- 28441900
TI  - Placental NFE2L2 is discordantly activated in monochorionic twins with selective
      intrauterine growth restriction and possibly regulated by hypoxia.
AB  - INTRODUCTION: Nuclear factor, erythroid 2 like 2 (NFE2L2) is an important
      transcription factor that protects cells from oxidative stress (OS). NFE2L2
      deficiency in placentas is associated with pregnancy complications. We have
      demonstrated that elevated OS existed in placental shares of the smaller fetus in
      selective intrauterine growth restriction (sIUGR); however, the role of NFE2L2 in
      the development of sIUGR remains unknown. In this study, we examined the levels
      of NFE2L2 and heme oxygenase 1 (HMOX1), a major antioxidant regulated by NFE2L2,
      in sIUGR placentas. We also investigated the relationship between hypoxia and
      NFE2L2 activation, which may be involved in the pathogenesis of sIUGR. METHODS:
      Real-time PCR, Western blot, and immunohistochemistry were used to detect the
      levels of NFE2L2 and HMOX1 in placentas from 30 monochorionic diamniotic (MCDA)
      twin pregnancies. The trophoblast cell line HTR-8/SVneo was cultured under severe
      (3%) or mild (10%) hypoxia. RESULTS: NFE2L2 and HMOX1 were both up-regulated in
      placental shares of the smaller fetus in the sIUGR group. No significant inter
      twin differences in NFE2L2 and HMOX1 were detected in the normal group. In vitro,
      NFE2L2 was suppressed under severe hypoxia (3% O2) but was clearly up-regulated
      under mild hypoxia (10% O2). DISCUSSION: Compared with the suppression of NFE2L2
      in placentas of fetal growth restriction (FGR) in singleton pregnancies, NFE2L2
      was up-regulated in placental shares of the smaller fetus in sIUGR pregnancies.
      The asymmetrical activation of NFE2L2 in placental shares of sIUGR twins may be a
      compensation for hypoxia that protects the smaller fetus from OS damage.

PMID- 28441901
TI  - Patient emergency assessment following deliberate self-poisoning with
      benzodiazepines: Can cognitive markers predict recall of the psychiatric
      interview? A pilot study.
AB  - STUDY HYPOTHESIS: In cases of deliberate self-poisoning (DSP), patients often
      ingest benzodiazepines (BZDs), known to alter memory. Experts recommend recovery
      of the patient's cognitive capacity before psychiatric assessment. Unfortunately,
      there is no validated tool in common practice to assess whether sufficient
      cognitive recovery has occurred after DSP with BZDs to ensure patient memory of
      the assessment. OBJECTIVE: The aim of the study was to identify cognitive
      functions and markers which predict preserved memory of the mental health care
      plan proposed at the emergency department after DSP. METHODS: We recruited
      patients admitted for DSP with BZDs and control patients. At the time of the
      psychiatric assessment, we performed cognitive tests and we studied the
      relationship between these tests and the scores of a memory test performed 24 h
      after. RESULTS: In comparison with the control group, we found memory impairment
      in the BZD group. We found significant impairment on the Trail Making Test A (TMT
      A) in the BZD group in comparison with the control group, while TMT A and
      Wechsler Adult Intelligence Scale (WAIS) Coding test scores were significantly
      correlated with memory scores. CONCLUSIONS: Attentional functions tested by WAIS
      Coding test and TMT A were correlated with memory score. It could be profitable
      to assess it in clinical practice prior to a psychiatric interview.

PMID- 28441903
TI  - Age, criterion flexibility, and item recognition.
AB  - We examined young and older adults' ability to flexibly adapt response criterion
      on a recognition test when the probability that a test item had been studied was
      cued by test color. One word color signaled that the probability of the test item
      being old was 70% and a second color signaled that the probability of the test
      item being new was 70%. Young and older adults demonstrated similar levels of
      criterion shifting in response to color cues. Moreover, although both young and
      older adults were slowed when test-item color incorrectly predicted test-item
      status, the extent of slowing did not differ across age group. Putative measures
      of cognitive control predicted recognition accuracy but not the degree to which
      criterion changed with test-item color. These results suggest that adaptive
      criterion shifting does not tax cognitive control or, if it does require effort,
      may be no more onerous for older than for young adults.

PMID- 28441904
TI  - The safety of ustekinumab for the treatment of psoriatic arthritis.
AB  - INTRODUCTION: The cytokines interleukin (IL)-12 and IL-23 have been involved in
      the pathogenesis of psoriasis and psoriatic arthritis. Ustekinumab is a fully
      human monoclonal antibody targeting the p40 subunit shared by IL-12 and IL-23.
      Ustekinumab prevents the interaction of IL-12 and IL-23 binding to their
      receptors, blocking the T1 and T17 inflammatory pathways. Ustekinumab has been
      evaluated for the treatment of various chronic immune mediated diseases including
      psoriasis and psoriatic arthritis (PsA). Most of the data regarding the safety of
      ustekinumab come from the experience treating patients with psoriasis, but
      clinical trials have demonstrated its efficacy and safety in the treatment of
      both diseases. The most common adverse events observed during the clinical trials
      are mild in intensity, and include respiratory tract infections, nasopharyngitis,
      headache and injection site reactions. Throughout long-term ustekinumab
      treatment, serious infections or major cardiovascular adverse events occurred
      rarely. Areas covered: In this review we report the safety data that come from
      phase II and phase III clinical trials that assay the efficacy and safety of
      ustekinumab in PsA, including recently published data corresponding to long-term
      studies. Relevant references were obtained through a literature search in
      MEDLINE/Pubmed (search strategy: ustekinumab AND psoriatic arthritis) for
      articles published until November 2016, complemented by a manual search. Expert
      opinion: In clinical practice, ustekinumab is generally a well-tolerated
      treatment, and the safety profile in psoriatic arthritis is similar to that
      reported in plaque psoriasis.

PMID- 28441902
TI  - Nonhuman primates as models for the discovery and development of radiation
      countermeasures.
AB  - INTRODUCTION: Despite significant scientific advances over the past six decades
      toward the development of safe and effective radiation countermeasures for humans
      using animal models, only two pharmaceutical agents have been approved by United
      States Food and Drug Administration (US FDA) for hematopoietic acute radiation
      syndrome (H-ARS). Additional research efforts are needed to further develop large
      animal models for improving the prediction of clinical safety and effectiveness
      of radiation countermeasures for ARS and delayed effects of acute radiation
      exposure (DEARE) in humans. Area covered: The authors review the suitability of
      animal models for the development of radiation countermeasures for ARS following
      the FDA Animal Rule with a special focus on nonhuman primate (NHP) models of ARS.
      There are seven centers in the United States currently conducting studies with
      irradiated NHPs, with the majority of studies being conducted with rhesus
      monkeys. Expert opinion: The NHP model is considered the gold standard animal
      model for drug development and approval by the FDA. The lack of suitable
      substitutes for NHP models for predicting response in humans serves as a
      bottleneck for the development of radiation countermeasures. Additional large
      animal models need to be characterized to support the development and FDA
      approval of new radiation countermeasures.

PMID- 28441905
TI  - Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in
      the sub-chronic PCP-model for schizophrenia: A preliminary investigation.
AB  - RATIONALE: Dopamine dysregulation in the prefrontal cortex (PFC) plays an
      important role in cognitive dysfunction in schizophrenia. Sub-chronic
      phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is
      a thoroughly validated animal model for cognitive deficits in schizophrenia. The
      aim of our study was to investigate the role of PFC dopamine in scPCP-induced
      deficits in a cognitive task of relevance to the disorder, novel object
      recognition (NOR). METHODS: Twelve adult female Lister Hooded rats received scPCP
      (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days,
      followed by 7 days washout. In vivo microdialysis was carried out prior to,
      during and following the NOR task. RESULTS: Vehicle rats successfully
      discriminated between novel and familiar objects and this was accompanied by a
      significant increase in dopamine in the PFC during the retention trial ( p <
      0.01). scPCP produced a significant deficit in NOR ( p < 0.05 vs. control) and no
      PFC dopamine increase was observed. CONCLUSIONS: These data demonstrate an
      increase in dopamine during the retention trial in vehicle rats that was not
      observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP
      group. This novel finding suggests a mechanism by which cognitive deficits are
      produced in this animal model and support its use for investigating disorders in
      which PFC dopamine is central to the pathophysiology.

PMID- 28441906
TI  - Setting priorities for EU healthcare workforce IT skills competence improvement.
AB  - A major challenge for healthcare quality improvement is the lack of IT skills and
      knowledge of healthcare workforce, as well as their ambivalent attitudes toward
      IT. This article identifies and prioritizes actions needed to improve the IT
      skills of healthcare workforce across the EU. A total of 46 experts, representing
      different fields of expertise in healthcare and geolocations, systematically
      listed and scored actions that would improve IT skills among healthcare
      workforce. The Child Health and Nutrition Research Initiative methodology was
      used for research priority-setting. The participants evaluated the actions using
      the following criteria: feasibility, effectiveness, deliverability, and maximum
      impact on IT skills improvement. The leading priority actions were related to
      appropriate training, integrating eHealth in curricula, involving healthcare
      workforce in the eHealth solution development, improving awareness of eHealth,
      and learning arrangement. As the different professionals' needs are prioritized,
      healthcare workforce should be actively and continuously included in the
      development of eHealth solutions.

PMID- 28441907
TI  - Leg massage by mother resulting in fatal pulmonary thromboembolism.
AB  - We report the sudden death of a 23-year-old male with hairline ankle fracture
      after massage of the leg by his mother. Autopsy confirmed the cause of death as
      pulmonary thromboembolism due to deep vein thrombosis of the leg veins which was
      dislodged and travelled to his lungs consequent to the leg massage. The treating
      doctors did not warn the patient of the risk of developing pulmonary
      thromboembolism.

PMID- 28441908
TI  - Glucose-fructose ingestion and exercise performance: The gastrointestinal tract
      and beyond.
AB  - Carbohydrate ingestion can improve endurance exercise performance. In the past
      two decades, research has repeatedly reported the performance benefits of
      formulations comprising both glucose and fructose (GLUFRU) over those based on
      glucose (GLU). This has been usually related to additive effects of these two
      monosaccharides on the gastrointestinal tract whereby intestinal carbohydrate
      absorption is enhanced and discomfort limited. This is only a partial
      explanation, since glucose and fructose are also metabolized through different
      pathways after being absorbed from the gut. In contrast to glucose that is
      readily used by every body cell type, fructose is specifically targeted to the
      liver where it is mainly converted into glucose and lactate. The ingestion of
      GLUFRU may thereby profoundly alter hepatic function ultimately raising both
      glucose and lactate fluxes. During exercise, this particular profile of
      circulating carbohydrate may induce a spectrum of effects on muscle metabolism
      possibly resulting in an improved performance. Compared to GLU alone, GLUFRU
      ingestion could also induce several non-metabolic effects which are so far
      largely unexplored. Through its metabolite lactate, fructose may act on central
      fatigue and/or alter metabolic regulation. Future research could further define
      the effects of GLUFRU over other exercise modalities and different athletic
      populations, using several of the hypotheses discussed in this review.

PMID- 28441909
TI  - The perceived quality of in-vehicle auditory signals: a structural equation
      modelling approach.
AB  - The current study applied Structural Equation Modelling to analyse the
      relationship among pitch, loudness, tempo and timbre and their relationship with
      perceived sound quality. Twenty-eight auditory signals of horn, indicator, door
      open warning and parking sensor were collected from 11 car brands. Twenty-one
      experienced drivers were recruited to evaluate all sound signals with 11 semantic
      differential scales. The results indicate that for the continuous sounds, pitch,
      loudness and timbre each had a direct impact on the perceived quality. Besides
      the direct impacts, pitch also had an impact on loudness perception. For the
      intermittent sounds, tempo and timbre each had a direct impact on the perceived
      quality. These results can help to identify the psychoacoustic attributes
      affecting the consumers' quality perception and help to design preferable sounds
      for vehicles. In the end, a design guideline is proposed for the development of
      auditory signals that adopts the current study's research findings as well as
      those of other relevant research. Practitioner Summary: This study applied
      Structural Equation Modelling to analyse the relationship among pitch, loudness,
      tempo and timbre and their relationship with perceived sound quality. The result
      can help to identify psychoacoustic attributes affecting the consumers' quality
      perception and help to design preferable sounds for vehicles.

PMID- 28441910
TI  - Mechanical features of various silkworm crystalline considering hydration effect
      via molecular dynamics simulations.
AB  - Silk materials are receiving significant attention as base materials for various
      functional nanomaterials and nanodevices, due to its exceptionally high
      mechanical properties, biocompatibility, and degradable characteristics. Although
      crystalline silk regions are composed of various repetitive motifs with differing
      amino acid sequences, how the effect of humidity works differently on each of the
      motifs and their structural characteristics remains unclear. We report molecular
      dynamics (MD) simulations on various silkworm fibroins composed of major motifs
      (i.e. (GAGAGS)n, (GAGAGA)n, and (GAGAGY)n) at varying degrees of hydration, and
      reveal how each major motifs of silk fibroins change at each degrees of hydration
      using MD simulations and their structural properties in mechanical perspective
      via steered molecular dynamics simulations. Our results explain what effects
      humidity can have on nanoscale materials and devices consisting of crystalline
      silk materials.

PMID- 28441911
TI  - The effects of a data driven maximum surgical blood ordering schedule on
      preoperative blood ordering practices.
AB  - OBJECTIVES: The maximum surgical blood ordering schedule (MSBOS) provides
      guidelines for pre-operative pre-transfusion testing for elective surgical
      procedures. This study compared blood ordering and utilization during the period
      when the MSBOS was created by achieving consensus between the blood bank and the
      various surgical specialties, and after the introduction of an MSBOS created by
      using department-specific red blood cell (RBC) transfusion data (data driven
      MSBOS, dMSBOS). METHODS: The dMSBOS was created by analyzing 12 months of RBC
      transfusion data for each procedure across a regional health system. Pre
      transfusion testing and the RBC crossmatch:transfusion (C:T) ratios at 8 of the
      hospitals were compared between the 12 month period before the dMSBOS was
      introduced, and the 15 months after its introduction. RESULTS: There were
      significant reductions in the median monthly number of type and screens not
      associated with RBC crossmatches (10 714-10 061; p < 0.0001) and the median
      number of type and screens associated with RBC crossmatches (10 127-9 349; p =
      0.0014) on surgical patients after dMSBOS implementation. There were significant
      decreases in the median number of monthly RBC units crossmatched (2 981-2 444; p
      < 0.0001) and transfused (890-791; p < 0.0001) to surgical patients after
      implementing the dMSBOS. The overall system-wide C:T ratio trended down after
      dMSBOS implementation (from 3.34 to 3.17, p = 0.067). DISCUSSION: Crossmatching
      fewer RBC units facilitates more efficient management of the blood bank's
      inventory. CONCLUSION: The dMSBOS was effective in reducing the extent of
      unnecessary pre-transfusion testing before surgery and reduced the number of RBCs
      that were crossmatched for specific patients.

PMID- 28441913
TI  - The masquerading presentation of a systemic anaplastic large cell lymphoma, ALK
      positive: a case report and review of the literature.
AB  - We report an unusual case of systemic anaplastic large cell lymphoma (ALCL), ALK
      positive with leukemic involvement in a 57-year-old woman. The patient presented
      with a fulminant respiratory infection unresponsive to treatment requiring
      intensive care and ventilatory support. The CT scan demonstrated mediastinal and
      bilateral lymphadenopathy. On peripheral smear a few atypical lymphocytes were
      visualized. Based on the increasing number of atypical lymphocytes in the daily
      peripheral bloodsmears, the diagnosis ALCL was suggested. Definitive diagnosis
      was made on a bone marrow biopsy, with lymphocytes being immunoreactive for CD30,
      EMA, and ALK. Leukemic peripheral blood involvement in ALCL is an uncommon
      clinicopathologic entity with unfavorable prognosis. The case we present is
      perhaps unusual in that a complete respons was achieved, highlighting the
      importance of prompt diagnosis and judicious management.

PMID- 28441914
TI  - Systematic review of the literature on reproducibility of the interpretation of
      renal biopsy in lupus nephritis.
AB  - Objective Before using a test, it should be determined whether the results are
      reliable. The reliability of the interpretation of renal biopsy in patients with
      lupus nephritis has not been clearly elucidated. Our objective was to estimate
      inter and intra-observer reliability of the histological classification, as well
      as activity and chronicity indices in renal biopsy of patients with lupus
      nephritis. Methods We conducted a systematic search of the literature, which
      included articles in any language, using PubMed, Embase, Cochrane and Lilacs
      databases. Search terms included were: reproducibility, reliability, agreement,
      systemic lupus erythematosus and lupus nephritis. Comparative studies with any
      design were included, regardless of the year or the language of publication. Two
      investigators, independently, screened the literature published in accordance
      with pre-established inclusion and exclusion criteria. Results We found 13
      relevant studies. Inter-observer reproducibility of most measurements was
      moderate or low, despite the fact that, in most cases, the readings were made by
      expert nephropathologists. There was great diversity among designs, participants,
      including samples and outcomes evaluated in different studies. Although there are
      too many reports on the clinical use, studies evaluating the reliability of
      classifications on renal biopsy in lupus nephritis are rare. The quality of the
      methodological design and reporting was fair. Conclusion The interpretation of
      renal biopsy in lupus nephritis is poorly reproducible, causing serious doubts
      about its validity and its clinical application. As it can lead to serious
      diagnosis, treatment and prognosis errors, it is necessary to intensify research
      in this field.

PMID- 28441915
TI  - Early-life adversity-induced long-term epigenetic programming associated with
      early onset of chronic physical aggression: Studies in humans and animals.
AB  - OBJECTIVES: To examine whether chronic physical aggression (CPA) in adulthood can
      be epigenetically programmed early in life due to exposure to early-life
      adversity. METHODS: Literature search of public databases such as PubMed/MEDLINE
      and Scopus. RESULTS: Children/adolescents susceptible for CPA and exposed to
      early-life abuse fail to efficiently cope with stress that in turn results in the
      development of CPA later in life. This phenomenon was observed in humans and
      animal models of aggression. The susceptibility to aggression is a complex trait
      that is regulated by the interaction between environmental and genetic factors.
      Epigenetic mechanisms mediate this interaction. Subjects exposed to stress early
      in life exhibited long-term epigenetic programming that can influence their
      behaviour in adulthood. This programming affects expression of many genes not
      only in the brain but also in other systems such as neuroendocrine and immune.
      CONCLUSIONS: The propensity to adult CPA behaviour in subjects experienced to
      early-life adversity is mediated by epigenetic programming that involves long
      term systemic epigenetic alterations in a whole genome.

PMID- 28441916
TI  - Impact of surgical margins on survival of 37 dogs with massive hepatocellular
      carcinoma.
AB  - AIMS: To compare the survival of dogs with completely resected massive
      hepatocellular carcinoma (HCC) with that of dogs in which HCC were incompletely
      excised. METHODS: A retrospective cohort study was conducted. Dogs that underwent
      surgical excision of massive HCC between November 2006 and April 2015 were
      included. Dogs that died in the perioperative period or were lost to follow-up
      within 2 months after surgery were excluded. Data were collected from the medical
      records and a single pathologist examined all available histology slides to
      confirm the diagnosis of HCC. Surgical margins were defined as complete if no
      neoplastic cells were seen at the edge of excised tissues, based on original
      histopathology reports. Progression-free survival (PFS) and overall survival (OS)
      were compared between dogs with complete surgical margins (CM) and those with
      incomplete margins (IM) using a log-rank test. RESULTS: Of the 37 dogs included
      in the study, 25 were allocated to the CM group and 12 to the IM group.
      Progressive local disease developed after surgery in three dogs in the CM group
      and seven dogs in the IM group. Three dogs in the CM group and five dogs in the
      IM group died due to tumour progression. Median PFS was longer for dogs in the CM
      group (1,000 (95% CI=562-1,438) days) compared to dogs in the IM group (521 (95%
      CI=243-799) days; p=0.007). OS was also longer for dogs in the CM group (>1,836
      days) compared to those in the IM group (median 765 (95% CI=474-1,056) days;
      p=0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Compared with complete resection,
      incomplete resection decreased PFS and OS in dogs with massive HCC. Dogs with
      incompletely excised HCC should be closely monitored for local recurrence,
      although median OS was >2 years following incomplete excision. Further
      prospective studies are warranted to confirm these findings.

PMID- 28441917
TI  - Identification of IL-17A-derived neural cell type and dynamic changes of IL-17A
      in serum/CSF of mice with ischemic stroke.
AB  - BACKGROUND: Interleukin (IL)-17A was reported to be involved in the development
      of post-ischemic stroke inflammatory response and functional recovery. However,
      the IL-17A dynamic changes in serum/cerebrospinal fluid (CSF) and its role in
      neuronal injury following ischemic stroke are unclear. METHODS: In vivo ischemic
      stroke was induced by 1 h of middle cerebral artery occlusion (MCAO) and 6 h-7 d
      reperfusion (R) in mice, while in vitro stroke was induced by 1 h oxygen-glucose
      deprivation (OGD)/24 h reoxygenation (R) in cultured cortical neurons. Enzyme
      linked immunosorbent assay (ELISA) and double-labeled immunofluorescence of IL
      17A with neuron (NeuN), astrocyte (GFAP) and microglia (Iba-1)-specific markers
      were used to determine the IL-17A levels in serum/CSF and neural cell type.
      RESULTS: The ELISA results showed that IL-17A significantly increased both in
      peri-infarct region (p < 0.001) and CSF (p < 0.05) following 1 h MCAO/R 12 h. The
      levels of IL-17A in serum increased at R 1 d (p < 0.05) and peaked at R 3 d (p <
      0.001) after 1 h MCAO. Immunofluorescent staining demonstrated that IL-17A co
      localized with GFAP in peri-infarct regions. In addition, recombinant rIL-17A
      could aggravate ischemic injuries at dose-dependent manner in 1 h OGD/R 24 h
      treated neurons companying with the increase of IL-17A receptor il-17RA mRNA (p <
      0.001) and IL-17R protein levels. CONCLUSION: We firstly reported astrocytic IL
      17A peaks in CSF within 12 h and in serum at 3 d reperfusion after ischemic
      stroke. IL-17A may exaggerate neuronal injuries through its receptor IL-17R at
      early stage of ischemic stroke.

PMID- 28441918
TI  - Molecular dynamics simulations indicate that deoxyhemoglobin, oxyhemoglobin,
      carboxyhemoglobin, and glycated hemoglobin under compression and shear exhibit an
      anisotropic mechanical behavior.
AB  - We developed a new mechanical model for determining the compression and shear
      mechanical behavior of four different hemoglobin structures. Previous studies on
      hemoglobin structures have focused primarily on overall mechanical behavior;
      however, this study investigates the mechanical behavior of hemoglobin, a major
      constituent of red blood cells, using steered molecular dynamics (SMD)
      simulations to obtain anisotropic mechanical behavior under compression and shear
      loading conditions. Four different configurations of hemoglobin molecules were
      considered: deoxyhemoglobin (deoxyHb), oxyhemoglobin (HbO2), carboxyhemoglobin
      (HbCO), and glycated hemoglobin (HbA1C). The SMD simulations were performed on
      the hemoglobin variants to estimate their unidirectional stiffness and shear
      stiffness. Although hemoglobin is structurally denoted as a globular protein due
      to its spherical shape and secondary structure, our simulation results show a
      significant variation in the mechanical strength in different directions
      (anisotropy) and also a strength variation among the four different hemoglobin
      configurations studied. The glycated hemoglobin molecule possesses an overall
      higher compressive mechanical stiffness and shear stiffness when compared to
      deoxyhemoglobin, oxyhemoglobin, and carboxyhemoglobin molecules. Further results
      from the models indicate that the hemoglobin structures studied possess a soft
      outer shell and a stiff core based on stiffness.

PMID- 28441919
TI  - Si-based technologies for reduction of the pollutant leaching from landfills and
      mine tails.
AB  - Monosilicic and polysilicic acids were shown to react with different types of the
      pollutants. The direction of these reactions can be managed by changing the
      monosilicic and polysilicic acid concentration in soil or water media. The
      objective of this study was to determine the effect of Si-treated calcium
      metallurgical slag and battery slag on the As, Se, Cd, Pb, Ni, Cr, and Hg
      mobility and bioavailability in mine tailings (Xikuangshan mine, Hunan, China).
      The results of column experiment showed that the Si-activated slags reduced
      leaching of As, Se, Cd, Pb, Ni, Cr, and Hg by 13-89% and transformed them into
      plant-unavailable forms. The greenhouse test has demonstrated that the Si-treated
      slags provided reinforced plant resistance to heavy metal toxicity and reduced
      pollutants in barley and pea leaves. Si-treated local solid slags could be used
      for creating the biogeochemical barriers on the pollutant streams from landfills
      or mine tailings sites.

PMID- 28441920
TI  - Investigational Janus kinase inhibitors in development for myelofibrosis.
AB  - INTRODUCTION: Since the discovery of the activating V617F mutation in Janus
      kinase 2 (JAK2), a number of pharmacologic inhibitors of JAK2 have entered
      clinical trials for patients with myelofibrosis. However, ruxolitinib, approved
      in 2011, remains the only one currently available for treatment of myelofibrosis,
      with many others having been discontinued for toxicity, and considerable
      uncertainty surrounding the future of those still in development. Areas covered:
      The available clinical data on pacritinib and momelotinib, the two agents in the
      most advanced phases of clinical testing in myelofibrosis, are examined in
      detail. NS-018 and INCB039110, selective inhibitors of JAK2 and JAK1,
      respectively, are also discussed. Finally, the JAK2 inhibitors no longer in
      clinical development are summarized in tabular form. Expert opinion: The
      different agents evaluated clearly differ in their kinomes, toxicity profiles and
      potential for myelosuppression. If approved, the JAK2-specific non
      myelosuppressive inhibitor pacritinib could fulfill a major unmet need, that of
      patients with significant cytopenias. However, toxicity concerns persist. The
      data from the pivotal trials of momelotinib do not support its approval, although
      improvement of anemia is an important benefit. Selective JAK1 inhibition alone is
      unlikely to succeed in myelofibrosis. In these circumstances, rational
      ruxolitinib-based combinations may represent the best way forward.

PMID- 28441921
TI  - Acquired hemophilia A: a review of recent data and new therapeutic options.
AB  - OBJECTIVES: Acquired hemophilia A (AHA) is a rare, but potentially life
      threatening, bleeding disorder caused by an autoantibody against factor VIII that
      interferes with its coagulant function. METHODS: We performed a narrative review
      focusing on the diagnostic aspects of AHA and on the current treatment strategies
      with particular regard to new data and therapeutic developments. RESULTS: The
      management of this severe hemorrhagic disorder is based on the control of
      bleeding with the use of bypassing agents and on the utilization of a variety of
      immunosuppressant agents with the goal of eliminating the autoantibody
      permanently. CONCLUSION: The optimal management of AHA should be
      multidisciplinary and requires a close collaboration between physicians from
      various specialties.

PMID- 28441922
TI  - Fluid displacement from intraluminal thrombus of abdominal aortic aneurysm as a
      result of uniform compression.
AB  - Objectives The results after aneurysm repair with an endovascular aneurysm
      sealing (EVAS) system are dependent on the stability of the aneurysm sac and
      particularly the intraluminal abdominal aortic thrombus (ILT). The postprocedural
      ILT volume is decreased compared with preprocedural ILT volume in aortic aneurysm
      patients treated with EVAS. We hypothesize that ILT is not stable in all patients
      and pressurization of the ILT may result in displacement of fluids from the ILT,
      no differently than serum is displaced from whole blood when it settles. To date,
      the mechanism and quantification of fluid displacement from ILT are unknown.
      Methods The study included 21 patients who underwent elective open abdominal
      aortic aneurysm repair. The ILT was harvested as a routine procedure during the
      operation. After excision of a histologic sample of the ILT specimen in four
      patients, ILT volume was measured and the ILT was compressed in a dedicated
      compression setup designed to apply uniform compression of 200 mmHg for 5 min.
      After compression, the volumes of the remaining thrombus and the displaced fluid
      were measured. Results The median (interquartile-range) of ILT volume before
      compression was 60 (66) mL, and a median of 5.7 (8.4) mL of fluid was displaced
      from the ILT after compression, resulting in a median thrombus volume decrease of
      11% (10%). Fluid components can be up to 31% of the entire ILT volume. Histologic
      examination of four ILT specimens showed a reduction of the medial layer of the
      ILT after compression, which was the result of compression of fluid-containing
      canaliculi. Conclusions Applying pressure of 200 mmHg to abdominal aortic
      aneurysm ILT resulted in the displacement of fluid, with a large variation among
      patients. Fluid displacement may result in decrease of ILT volume during and
      after EVAS, which might have implications on pre-EVAS volume planning and on
      stability of the endobags during follow-up which may lead to migration, endoleak
      or both.

PMID- 28441923
TI  - Lowered PON1 activities are strongly associated with depression and bipolar
      disorder, recurrence of (hypo)mania and depression, increased disability and
      lowered quality of life.
AB  - OBJECTIVES: Mood disorders (MDs) frequently co-exist with cardiovascular disease
      (CVD) and immune-inflammatory and oxidative stress are important shared
      pathophysiological pathways. Even though there has been an extensive
      investigation of the enzyme paraoxonase 1 (PON1) as a biomarker of susceptibility
      for CVD, there are few reports studying PON1 in MDs. The aim of this study was to
      determine the association between PON1 activities as well as functional genotypes
      and MD diagnosis, clinical characteristics and outcomes. METHODS: PON1 activities
      and functional genotypes were assayed in 58 bipolar disorder (BD) and 32 major
      depressed patients (MDD) and compared with 59 controls. RESULTS: Our findings
      show significantly lower PON1 total and CMPAase activities in MDs, which are
      partly related to the number of previous depressive and manic episodes. Lowered
      CMPAase activity is associated with a worse outcome of MDs as indicated by
      lowered quality of life (WHOQoL-BREF scale) and increased disability in the
      Sheeham scale. CONCLUSIONS: We hypothesise that lowered PON1 total and CMPAase
      activities may play a role in the pathophysiology of MDs by lowering antioxidant
      defences thereby increasing the risk of lipid peroxidation and inflammation;
      lowered inhibition of quorum-sensing lactones thereby increasing bacterial
      proliferation; and attenuated homocysteine thiolactone catabolism which may
      trigger immune-inflammatory response and/or induce neurotoxicity.

PMID- 28441925
TI  - Maternal and child health in Africa for sustainable development goals beyond
      2015.

PMID- 28441926
TI  - Timing and utilisation of antenatal care service in Nigeria and Malawi.
AB  - As the world draws curtains on the implementation of Millennium Development Goals
      (MDGs), there is increasing interest in evaluating the performance of countries
      on the goals and assessing related challenges and opportunities to inform the
      upcoming Sustainable Development Goals (SDGs). This study examined changes in the
      timing and utilisation of maternal health care services in Nigeria and Malawi;
      using multivariate negative log-log and logistic regression models fitted to
      demographic and health survey data sets. Predicted probabilities were also
      computed to observe the net differences in the likelihood of both the first and
      the required number of antenatal care (ANC) visits for each of the three analysis
      years. Women in Nigeria were 7% less likely in 2008 compared to 2003, and in
      Malawi, 32% more likely in 2013 compared to 2000, to utilise ANC in the first
      trimester of pregnancy. Timing of first ANC visit was strongly influenced by
      wealth in Nigeria but not in Malawi. The findings in our case studies show how
      various contextual factors may enable or inhibit policy performance. Maternal and
      child health, SDGs should incorporate both wealth and degrees of urbanicity into
      country level implementation strategies.

PMID- 28441927
TI  - Utilisation of skilled birth attendants over time in Nigeria and Malawi.
AB  - Despite recent modest progress in reducing maternal and infant mortality rates in
      sub-Saharan Africa, Nigeria and Malawi were still in the top 20 countries with
      highest rates of mortalities globally in 2015. Utilisation of professional
      services at delivery - one of the indictors of MDG 5 - has been suggested to
      reduce maternal mortality by 50%. Yet, contextual, socio-cultural and economic
      factors have served as barriers to uptake of such critical service. In this
      paper, we examined the impact of residential wealth index on utilisation of
      Skilled Birth Attendant in Nigeria (2003, 2008 and 2013), and Malawi (2000, 2004
      and 2010) using Demographic and Health Survey data sets. The findings from
      multivariate logistic regressions show that women in Nigeria were 23% less likely
      to utilise skilled delivery services in 2013 compared to 2003. In Malawi, women
      were 75% more likely to utilise skilled delivery services in 2010 than in 2000.
      Residential wealth index was a significant predictor of utilisation of skilled
      delivery services over time in both Nigeria and Malawi. These findings illuminate
      progress made - based on which we make recommendations for achievement of SDG-3:
      ensure healthy lives and promote well-being for all at all ages in Nigeria and
      Malawi, and similar context.

PMID- 28441928
TI  - Canadian Stroke Best Practice Recommendations: Telestroke Best Practice
      Guidelines Update 2017.
AB  - Every year, approximately 62,000 people with stroke and transient ischemic attack
      are treated in Canadian hospitals. The 2016 update of the Canadian Stroke Best
      Practice Recommendations Telestroke guideline is a comprehensive summary of
      current evidence-based and consensus-based recommendations appropriate for use by
      all healthcare providers and system planners who organize and provide care to
      patients following stroke across a broad range of settings. These recommendations
      focus on the use of telemedicine technologies to rapidly identify and treat
      appropriate patients with acute thrombolytic therapies in hospitals without
      stroke specialized expertise; select patients who require to immediate transfer
      to stroke centers for Endovascular Therapy; and for the patients who remain in
      community hospitals to facilitate their care on a stroke unit and provide remote
      access to stroke prevention and rehabilitation services. While these latter areas
      of Telestroke application are newer, they are rapidly developing, with new
      opportunities that are yet unrealized. Virtual rehabilitation therapies offer
      patients the opportunity to participate in rehabilitation therapies, supervised
      by physical and occupational therapists. While not without its limitations (e.g.,
      access to telecommunications in remote areas, fragmentation of care), the
      evidence-to-date sets the foundation for improving access to care and management
      for patients during both the acute phase and now through post stroke recovery.

PMID- 28441929
TI  - Endothelial progenitor cells and plaque burden in stented coronary artery
      segments: an optical coherence tomography study six months after elective PCI.
AB  - BACKGROUND: Endothelial progenitor cells (EPC) are involved in neovascularization
      and endothelial integrity. They might be protective in atherosclerosis. Optical
      coherence tomography (OCT) is a precise intracoronary imaging modality that
      allows assessment of subintimal plaque development. We evaluated the influence of
      EPC on coronary plaque burden in stable disease and implemented a novel
      computational plaque analysis algorithm using OCT. METHODS: Forty-three patients
      (69.8% males, 69.6 +/- 7.7 years) were investigated by OCT during re-angiography
      6 months after elective stent implantation. Different subpopulations of EPCs were
      identified by flow cytometry according to their co-expression of antigens (CD34+,
      CD133+, kinase domain receptor, KDR+). An algorithm was applied to calculate the
      underlying total plaque burden of the stented segments from OCT images. Plaque
      morphology was assessed according to international consensus in OCT imaging.
      RESULTS: A cumulative sub-strut plaque volume of 10.87 +/- 12.7 mm3 and a sub
      stent plaque area of 16.23 +/- 17.0 mm2 were found within the stented vessel
      segments with no significant differences between different stent types. All EPC
      subpopulations (mean of EPC levels: CD34+/CD133+: 2.66 +/- 2.0%; CD34+/KDR+: 7.50
      +/- 5.0%; CD34+/CD133+/KDR+: 1.12 +/- 1.0%) inversely correlated with the
      identified underlying total plaque volume and plaque area (p <= 0.012).
      CONCLUSIONS: This novel analysis algorithm allows for the first time
      comprehensive quantification of coronary plaque burden by OCT and illustration as
      spread out vessel charts. Increased EPC levels are associated with less sub-stent
      coronary plaque burden which adds to previous findings of their protective role
      in atherosclerosis.

PMID- 28441930
TI  - Ribosomal subunit protein typing using matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the identification
      and discrimination of Aspergillus species.
AB  - BACKGROUND: Accurate identification of Aspergillus species is a very important
      subject. Mass spectral fingerprinting using matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS) is generally employed
      for the rapid identification of fungal isolates. However, the results are based
      on simple mass spectral pattern-matching, with no peak assignment and no
      taxonomic input. We propose here a ribosomal subunit protein (RSP) typing
      technique using MALDI-TOF MS for the identification and discrimination of
      Aspergillus species. The results are concluded to be phylogenetic in that they
      reflect the molecular evolution of housekeeping RSPs. RESULTS: The amino acid
      sequences of RSPs of genome-sequenced strains of Aspergillus species were first
      verified and compared to compile a reliable biomarker list for the identification
      of Aspergillus species. In this process, we revealed that many amino acid
      sequences of RSPs (about 10-60%, depending on strain) registered in the public
      protein databases needed to be corrected or newly added. The verified RSPs were
      allocated to RSP types based on their mass. Peak assignments of RSPs of each
      sample strain as observed by MALDI-TOF MS were then performed to set RSP type
      profiles, which were then further processed by means of cluster analysis. The
      resulting dendrogram based on RSP types showed a relatively good concordance with
      the tree based on beta-tubulin gene sequences. RSP typing was able to further
      discriminate the strains belonging to Aspergillus section Fumigati. CONCLUSIONS:
      The RSP typing method could be applied to identify Aspergillus species, even for
      species within section Fumigati. The discrimination power of RSP typing appears
      to be comparable to conventional beta-tubulin gene analysis. This method would
      therefore be suitable for species identification and discrimination at the strain
      to species level. Because RSP typing can characterize the strains within section
      Fumigati, this method has potential as a powerful and reliable tool in the field
      of clinical microbiology.

PMID- 28441931
TI  - Longitudinal trends in self-reported anxiety. Effects of age and birth cohort
      during 25 years.
AB  - BACKGROUND: Anxiety has been suggested to increase among young individuals, but
      previous studies on longitudinal trends are inconclusive. The aim of this study
      was to analyze longitudinally, the changes over time of prevalence of self
      reported anxiety in the Swedish population between 1980/1981 and 2004/2005, in
      different birth cohorts and age groups. METHODS: A random sample of non
      institutionalized persons aged 16-71 years was interviewed every eighth year.
      Self-reported anxiety was assessed using the question" Do you suffer from
      nervousness, uneasiness, or anxiety?" (no; yes, mild; yes, severe). Mixed models
      with random intercepts were used to estimate changes in rates of anxiety (mild or
      severe) within different age groups and birth cohorts and in males and females
      separately. In addition to three time-related variables - year of interview, age
      at the time of the interview, and year of birth -the following explanatory
      variables were included: education, urbanization, marital status, smoking,
      leisure time physical activity and body mass index. RESULTS: Overall prevalence
      of self-reported anxiety increased from 8.0 to 12.4% in males and from 17.8% to
      23.6% in females, during the 25-year follow-up period. The increasing trend was
      found in all age groups except in the oldest age groups, and the highest increase
      was found in young adults 16-23 years, with more than a three-fold increase in
      females, and a 2.5-fold increase in males, after adjustments for covariates.
      CONCLUSIONS: Between 1980/81 and 2004/05, there was an increasing prevalence of
      self-reported anxiety in all age groups except in the oldest, which indicates
      increased suffering for a large part of the population, and probably an increased
      burden on the health care system. Clinical efforts should focus particularly on
      young females (16-23 years), where the increase was particularly large; almost
      one third experienced anxiety at the end of the 25-year follow-up.

PMID- 28441932
TI  - An experimental comparison of web-push vs. paper-only survey procedures for
      conducting an in-depth health survey of military spouses.
AB  - BACKGROUND: Previous research has found that a "web-push" approach to data
      collection, which involves contacting people by mail to request an Internet
      survey response while withholding a paper response option until later in the
      contact process, consistently achieves lower response rates than a "paper-only"
      approach, whereby all respondents are contacted and requested to respond by mail.
      METHOD: An experiment was designed, as part of the Millennium Cohort Family
      Study, to compare response rates, sample representativeness, and cost between a
      web-push and a paper-only approach; each approach comprised 3 stages of mail
      contacts. The invited sample (n = 4,935) consisted of spouses married to U.S.
      Service members, who had been serving in the military between 2 and 5 years as of
      October, 2011. RESULTS: The web-push methodology produced a significantly higher
      response rate, 32.8% compared to 27.8%. Each of the 3 stages of postal contact
      significantly contributed to response for both treatments with 87.1% of the web
      push responses received over the Internet. The per-respondent cost of the paper
      only treatment was almost 40% higher than the web-push treatment group. Analyses
      revealed no meaningfully significant differences between treatment groups in
      representation. CONCLUSION: These results provide evidence that a web-push
      methodology is more effective and less expensive than a paper-only approach among
      young military spouses, perhaps due to their heavy reliance on the internet, and
      we suggest that this approach may be more effective with the general population
      as they become more uniformly internet savvy.

PMID- 28441933
TI  - Identification and biochemical characterization of the fructokinase gene family
      in Arabidopsis thaliana.
AB  - BACKGROUND: Fructose is an abundant sugar in plants as it is a breakdown product
      of both major sucrose-cleaving enzymes. To enter metabolism, fructose is
      phosphorylated by a fructokinase (FRK). Known FRKs are members of a diverse
      family of carbohydrate/purine kinases known as the phosphofructokinase B (pfkB)
      family. The complete complement of active fructokinases has not been reported for
      any plant species. RESULTS: Protein sequence analysis of the 22 Arabidopsis
      thaliana pfkB members identified eight highly related predicted proteins,
      including one with previously demonstrated FRK activity. For one, At1g50390, the
      predicted open reading frame is half the size of active FRKs, and only
      incompletely spliced RNAs were identified, which led to a premature stop codon,
      both indicating that this gene does not produce active FRK. The remaining seven
      proteins were expressed in E. coli and phosphorylated fructose specifically in
      vitro leading us to propose a unifying nomenclature (FRK1-7). Substrate
      inhibition was observed for fructose in all FRKs except FRK1. Fructose binding
      was on the same order of magnitude for FRK1-6, between 260 and 480 MUM. FRK7 was
      an outlier with a fructose Km of 12 MUM. ATP binding was similar for all FRKs and
      ranged between 52 and 280 MUM. YFP-tagged AtFRKs were cytosolic, except plastidic
      FRK3. T-DNA alleles with non-detectable wild-type RNAs in five of the seven
      active FRK genes produced no overt phenotype. We extended our sequence
      comparisons to include putative FRKs encoded in other plant sequenced genomes. We
      observed that different subgroups expanded subsequent to speciation. CONCLUSIONS:
      Arabidopsis thaliana as well as all other plant species analyzed contain multiple
      copies of genes encoding FRK activity. Sequence comparisons among multiple
      species identified a minimal set of three distinct FRKs present on all species
      investigated including a plastid-localized form. The selective expansion of
      specific isozymes results in differences in FRK gene number among species. AtFRKs
      exhibit substrate inhibition, typical of their mammalian counterparts with the
      single AtFRK1 lacking this property, suggesting it may have a distinct in vivo
      role. Results presented here provide a starting point for the engineering of
      specific FRKs to affect biomass production.

PMID- 28441934
TI  - Health literacy in childhood and youth: a systematic review of definitions and
      models.
AB  - BACKGROUND: Children and young people constitute a core target group for health
      literacy research and practice: during childhood and youth, fundamental
      cognitive, physical and emotional development processes take place and health
      related behaviours and skills develop. However, there is limited knowledge and
      academic consensus regarding the abilities and knowledge a child or young person
      should possess for making sound health decisions. The research presented in this
      review addresses this gap by providing an overview and synthesis of current
      understandings of health literacy in childhood and youth. Furthermore, the
      authors aim to understand to what extent available models capture the unique
      needs and characteristics of children and young people. METHOD: Six databases
      were systematically searched with relevant search terms in English and German. Of
      the n = 1492 publications identified, N = 1021 entered the abstract screening and
      N = 340 full-texts were screened for eligibility. A total of 30 articles, which
      defined or conceptualized generic health literacy for a target population of 18
      years or younger, were selected for a four-step inductive content analysis.
      RESULTS: The systematic review of the literature identified 12 definitions and 21
      models that have been specifically developed for children and young people. In
      the literature, health literacy in children and young people is described as
      comprising variable sets of key dimensions, each appearing as a cluster of
      related abilities, skills, commitments, and knowledge that enable a person to
      approach health information competently and effectively and to derive at health
      promoting decisions and actions. DISCUSSION: Identified definitions and models
      are very heterogeneous, depicting health literacy as multidimensional, complex
      construct. Moreover, health literacy is conceptualized as an action competence,
      with a strong focus on personal attributes, while also recognising its
      interrelatedness with social and contextual determinants. Life phase
      specificities are mainly considered from a cognitive and developmental
      perspective, leaving children's and young people's specific needs,
      vulnerabilities, and social structures poorly incorporated within most models.
      While a critical number of definitions and models were identified for youth or
      secondary school students, similar findings are lacking for children under the
      age of ten or within a primary school context.

PMID- 28441935
TI  - Direct and indirect effects of influenza vaccination.
AB  - BACKGROUND: After vaccination, vaccinees acquire some protection against
      infection and/or disease. Vaccination, therefore, reduces the number of
      infections in the population. Due to this herd protection, not everybody needs to
      be vaccinated to prevent infections from spreading. METHODS: We quantify direct
      and indirect effects of influenza vaccination examining the standard Susceptible
      Infected-Recovered (SIR) and Susceptible-Infected-Recovered-Susceptible (SIRS)
      model as well as simulation results of a sophisticated simulation tool which
      allows for seasonal transmission of four influenza strains in a population with
      realistic demography and age-dependent contact patterns. RESULTS: As shown
      analytically for the simple SIR and SIRS transmission models, indirect
      vaccination effects are bigger than direct ones if the effective reproduction
      number of disease transmission is close to the critical value of 1. Simulation
      results for 20-60% vaccination with live influenza vaccine of 2-17 year old
      children in Germany, averaged over 10 years (2017-26), confirm this result: four
      to seven times as many influenza cases are prevented among non-vaccinated
      individuals as among vaccinees. For complications like death due to influenza
      which occur much more frequently in the unvaccinated elderly than in the
      vaccination target group of children, indirect benefits can surpass direct ones
      by a factor of 20 or even more than 30. CONCLUSIONS: The true effect of
      vaccination can be much bigger than what would be expected by only looking at
      vaccination coverage and vaccine efficacy.

PMID- 28441936
TI  - Rationale and design of BISTRO: a randomized controlled trial to determine
      whether bioimpedance spectroscopy-guided fluid management maintains residual
      kidney function in incident haemodialysis patients.
AB  - BACKGROUND: Preserved residual kidney function (RKF) and normal fluid status are
      associated with better patient outcomes in incident haemodialysis patients. The
      objective of this trial is to determine whether using bioimpedance technology in
      prescribing the optimal post-dialysis weight can reduce the rate of decline of
      RKF and potentially improve patient outcomes. METHODS/DESIGN: 516 pateints
      commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine
      volume >500 ml per day or per the shorter inter-dialytic period will be consented
      and enrolled into a pragmatic, open-label, randomized controlled trial. The
      intervention is incorporation of bioimpedance spectroscopy (BI) determination of
      normally hydrated weight to set a post-dialysis target weight that limits volume
      depletion, compared to current standard practice. Clinicians and participants
      will be blinded to BI measures in the control group and a standardized record
      capturing management of fluid status will be used in all participants. Primary
      outcome is preservation of residual kidney function assessed as time to anuria
      (<=100 ml/day or <=200 ml urine volume in the short inter-dialytic period). A
      sample size of 516 was based upon a cumulative incidence of 30% anuria in the
      control group and 20% in the treatment group and 11% competing risks (death,
      transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes
      include rate of decline in small solute clearance, significant adverse events,
      hospitalization, loss of vascular access, cardiovascular events and
      interventions, dialysis efficacy and safety, dialysis-related symptoms and
      quality of life. Economic evaluation will be carried out to determine the cost
      effectiveness of the intervention. Analyses will be adjusted for patient
      characteristics and dialysis unit practice patterns relevant to fluid management.
      DISCUSSION: This trial will establish the added value of undertaking BI measures
      to support clinical management of fluid status and establish the relationship
      between fluid status and preservation of residual kidney function in incident
      haemodialysis patients. TRIAL REGISTRATION: ISCCTN Number: 11342007 , completed
      26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University.

PMID- 28441937
TI  - Observation of Zn-photoprotoporphyrin red Autofluorescence in human bronchial
      cancer using color-fluorescence endoscopy.
AB  - BACKGROUND: We observed red autofluorescence emanating from bronchial cancer
      lesions using a sensitive color-fluorescence endoscopy system. We investigated to
      clarify the origin of the red autofluorescence. METHODS: The wavelengths of the
      red autofluorescence emanating from lesions were measured in eight patients using
      a spectrum analyzer and compared based on pathologic findings. Red
      autofluorescence at 617.3, 617.4, 619.0, and 617.1 nm was emitted by normal
      bronchus, inflamed tissue, tissue exhibiting mild dysplasia, and malignant
      lesions, respectively. Protoporphyrin, uroporphyrin, and coproporphyrin, the
      major porphyrin derivatives in human blood, were purchased to determine which
      porphyrin derivative is the source of red fluorescence when acquired de novo. We
      synthesized photoporphyrin, Zn-protoporphyrin and Zn-photoprotoporphyrin from
      protoporphyrin. RESULTS: Coproporphyrin and uroporphyrin emitted only weak
      fluorescence. Fluorescence was emitted by our synthesized Zn-photoprotoporphyrin
      at 625.5 nm and by photoprotoporphyrin at 664.0 nm. CONCLUSIONS: From these
      results, we conclude that Zn-photoprotoporphyrin was the source of the red
      autofluorescence observed in bronchial lesions. Zn-protoporphyrin is converted to
      Zn-photoprotoporphyrin by radiation with excitation light. Our results suggest
      that red autofluorescence emanating from Zn-photoprotoporphyrin in human tissues
      could interfere with photodynamic diagnosis using porphyrin derivatives such as
      Photofrin(r) and Lazerphyrin(r) with a sensitive endoscopy system, because color
      cameras cannot differentiate Zn-photoprotoporphyrin red fluorescence from that of
      other porphyrin derivatives.

PMID- 28441938
TI  - MitoRS, a method for high throughput, sensitive, and accurate detection of
      mitochondrial DNA heteroplasmy.
AB  - BACKGROUND: Mitochondrial dysfunction is linked to numerous pathological states,
      in particular related to metabolism, brain health and ageing. Nuclear encoded
      gene polymorphisms implicated in mitochondrial functions can be analyzed in the
      context of classical genome wide association studies. By contrast, mitochondrial
      DNA (mtDNA) variants are more challenging to identify and analyze for several
      reasons. First, contrary to the diploid nuclear genome, each cell carries several
      hundred copies of the circular mitochondrial genome. Mutations can therefore be
      present in only a subset of the mtDNA molecules, resulting in a heterogeneous
      pool of mtDNA, a situation referred to as heteroplasmy. Consequently, detection
      and quantification of variants requires extremely accurate tools, especially when
      this proportion is small. Additionally, the mitochondrial genome has
      pseudogenized into numerous copies within the nuclear genome over the course of
      evolution. These nuclear pseudogenes, named NUMTs, must be distinguished from
      genuine mtDNA sequences and excluded from the analysis. RESULTS: Here we describe
      a novel method, named MitoRS, in which the entire mitochondrial genome is
      amplified in a single reaction using rolling circle amplification. This approach
      is easier to setup and of higher throughput when compared to classical PCR
      amplification. Sequencing libraries are generated at high throughput exploiting a
      tagmentation-based method. Fine-tuned parameters are finally applied in the
      analysis to allow detection of variants even of low frequency heteroplasmy. The
      method was thoroughly benchmarked in a set of experiments designed to demonstrate
      its robustness, accuracy and sensitivity. The MitoRS method requires 5 ng total
      DNA as starting material. More than 96 samples can be processed in less than a
      day of laboratory work and sequenced in a single lane of an Illumina HiSeq flow
      cell. The lower limit for accurate quantification of single nucleotide variants
      has been measured at 1% frequency. CONCLUSIONS: The MitoRS method enables the
      robust, accurate, and sensitive analysis of a large number of samples. Because it
      is cost effective and simple to setup, we anticipate this method will promote the
      analysis of mtDNA variants in large cohorts, and may help assessing the impact of
      mtDNA heteroplasmy on metabolic health, brain function, cancer progression, or
      ageing.

PMID- 28441939
TI  - Estimation of the severity of breathlessness in the emergency department: a
      dyspnea score.
AB  - BACKGROUND: Dyspnea is a frequent complaint in emergency departments (ED). It has
      a significant amount of subjective and affective components, therefore the
      dyspnea scores, based on the patients' rating, can be ambiguous. Our purpose was
      to develop and validate a simple scoring system to evaluate the severity of
      dyspnea in emergency care, based on objectively measured parameters. METHODS: We
      performed a double center, prospective, observational study including 350
      patients who were admitted in EDs with dyspnea. We evaluated the patients'
      subjective feeling about dyspnea and applied our Dyspnea Severity Score (DSS),
      rating the dyspnea in 7 Dimensions from 0 to 3 points. The DSS was validated
      using the deterioration of pH, base-excess and lactate levels in the blood gas
      samples (Objective Classification Scale (OCS) 9 points and 13 points groups).
      RESULTS: All of the Dimensions correlated closely with the OCS values and with
      the subjective feeling of the dyspnea. Using multiple linear regression analysis
      we were able to decrease the numbers of Dimensions from seven to four without
      causing a significant change in the determination coefficient in any OCS groups.
      This reduced DSS values (exercise tolerance, cooperation, cyanosis, SpO2 value)
      showed high sensitivity and specificity to predict the values of OCS groups (the
      ranges: AUC 0.77-0.99, sensitivity 65-100%, specificity 64-99%). There was a
      close correlation between the subjective dyspnea scores and the OCS point values
      (p < 0.001), though the scatter was very large. CONCLUSIONS: A new DSS was
      validated which score is suitable to compare the severity of dyspnea among
      different patients and different illnesses. The simplified version of the score
      (its value >=7 points without correction factors) can be useful at the triage or
      in pre-hospital care.

PMID- 28441940
TI  - Clinical records anonymisation and text extraction (CRATE): an open-source
      software system.
AB  - BACKGROUND: Electronic medical records contain information of value for research,
      but contain identifiable and often highly sensitive confidential information.
      Patient-identifiable information cannot in general be shared outside clinical
      care teams without explicit consent, but anonymisation/de-identification allows
      research uses of clinical data without explicit consent. RESULTS: This article
      presents CRATE (Clinical Records Anonymisation and Text Extraction), an open
      source software system with separable functions: (1) it anonymises or de
      identifies arbitrary relational databases, with sensitivity and precision similar
      to previous comparable systems; (2) it uses public secure cryptographic methods
      to map patient identifiers to research identifiers (pseudonyms); (3) it connects
      relational databases to external tools for natural language processing; (4) it
      provides a web front end for research and administrative functions; and (5) it
      supports a specific model through which patients may consent to be contacted
      about research. CONCLUSIONS: Creation and management of a research database from
      sensitive clinical records with secure pseudonym generation, full-text indexing,
      and a consent-to-contact process is possible and practical using entirely free
      and open-source software.

PMID- 28441941
TI  - Effect of previous utilization and out-of-pocket expenditure on subsequent
      utilization of a state led public-private partnership scheme "Chiranjeevi Yojana"
      to promote facility births in Gujarat, India.
AB  - BACKGROUND: In Gujarat, India, a state led public private partnership scheme to
      promote facility birth named Chiranjeevi Yojana (CY) was implemented in 2005.
      Institutional birth is provided free of cost at accredited private health
      facilities to women from socially disadvantaged groups (eligible women). CY has
      contributed in increasing facility birth and providing substantially subsidized
      (but not totally free) birth care; however, the retention of mothers in this
      scheme in subsequent child birth is unknown. Therefore, we conducted a study
      aimed to determine the effect of previous utilization of the scheme and previous
      out of pocket expenditure on subsequent child birth among multiparous eligible
      women in Gujarat. METHODS: This was a retrospective cohort study of multiparous
      eligible women (after excluding abortions and births at public facility). A
      structured questionnaire was administered by trained research assistant to those
      with recent delivery between Jan and Jul 2013. Outcome of interest was CY
      utilization in subsequent child birth (Jan-Jul 2013). Explanatory variables
      included socio-demographic characteristics (including category of eligibility),
      pregnancy related characteristics in previous child birth, before Jan 2013,
      (including CY utilization, out of pocket expenditure) and type of child birth in
      subsequent birth. A poisson regression model was used to assess the association
      of factors with CY utilization in subsequent child birth. RESULTS: Of 997
      multiparous eligible women, 289 (29%) utilized and 708 (71%) did not utilize CY
      in their previous child birth. Of those who utilized CY (n = 289), 182 (63%)
      subsequently utilized CY and 33 (11%) gave birth at home; whereas those who did
      not utilize CY (n = 708) had four times higher risk (40% vs. 11%) of subsequent
      child birth at home. In multivariable models, previous utilization of the scheme
      was significantly associated with subsequent utilization (adjusted Relative Risk
      (aRR): 2.7; 95% CI: 2.2-3.3), however previous out of pocket expenditure was not
      found to be associated with retention in the CY scheme. CONCLUSION: Women with
      previous CY utilization were largely retained; therefore, steps to increase
      uptake of CY are expected to increase retention of mothers within CY in their
      subsequent child birth. To understand the reasons for subsequent child birth at
      home despite previous CY utilization and previous zero/minimal out of pocket
      expenditure, future research in the form of systematic qualitative enquiry is
      recommended.

PMID- 28441942
TI  - Rare antibody-associated hemolytic transfusion reaction and transfusion-related
      acute lung injury: a case report.
AB  - BACKGROUND: Hemolytic transfusion reactions and transfusion-related acute lung
      injury (TRALI) are life-threatening complications associated with the transfusion
      of blood products. Hemorrhage is one of the most common surgical complications
      and the risk of bleeding is particularly acute in patients with hematologic
      deficiencies. Management of surgical bleeding can be divided into two phases. The
      first phase centers on immediate control of acute bleeding and the second phase
      focuses on keeping the patient stable and on reducing the sequelae associated
      with blood transfusions and blood loss. CASE PRESENTATION: We present the case of
      a 53-year-old woman with long-standing immune thrombocytopenia who underwent
      repair of a symptomatic ventral hernia. On post-operative day one the patient
      developed hemoperitoneum, requiring exploratory laparotomy and massive
      transfusion of blood products. The patient's recovery was complicated by
      consistently low hemoglobin, hematocrit and platelets, prompting frequent
      transfusion of additional blood products. Shortly after activation of the massive
      transfusion protocol, the patient developed TRALI. Compounding the situation, on
      post-operative day sixteen the patient's serum started to show hemolysis: lactate
      dehydrogenase (LDH) levels rose to 1,845 IU/L, with haptoglobin at less than 5.8
      mg/dL and with a high reticulocyte count (4.38%). Previous testing had shown that
      the patient was positive for most major antigens implicated in antibody formation
      and was only producing anti-E and anti-K antibodies (considered for all
      transfusions). Initial pre- and post-transfusion direct antiglobulin tests (DAT)
      were indeed negative. However, repeat DATs in the days following the noted serum
      changes were consistent with new allo-antibody formation. These findings prompted
      immediate withholding of all blood products and a thorough blood bank work up.
      Despite strong evidence for new allo-antibody formation, no specific known
      antibody could be identified. The patient recover well when blood products were
      withheld. DISCUSSION: We present the case of a 53-year-old woman with long
      standing immune thrombocytopenia who underwent repair of a symptomatic ventral
      hernia. On post-operative day one the patient developed hemoperitoneum, requiring
      exploratory laparotomy and massive transfusion of blood products. The patient's
      recovery was complicated by consistently low hemoglobin, hematocrit and
      platelets, prompting frequent transfusion of additional blood products. Shortly
      after activation of the massive transfusion protocol, the patient developed
      TRALI. Compounding the situation, on post-operative day sixteen the patient's
      serum started to show hemolysis: lactate dehydrogenase (LDH) levels rose to 1,845
      IU/L, with haptoglobin at less than 5.8 mg/dL and with a high reticulocyte count
      (4.38%). Previous testing had shown that the patient was positive for most major
      antigens implicated in antibody formation and was only producing anti-E and anti
      K antibodies (considered for all transfusions). Initial pre- and post-transfusion
      direct antiglobulin tests (DAT) were indeed negative. However, repeat DATs in the
      days following the noted serum changes were consistent with new allo-antibody
      formation. These findings prompted immediate withholding of all blood products
      and a thorough blood bank work up. Despite strong evidence for new allo-antibody
      formation, no specific known antibody could be identified. The patient recover
      well when blood products were withheld. Suspicion for hemolytic transfusion
      reactions should be high in patients with prior allo-antibody formation; these
      may present as acute hemolysis or as a delayed hemolytic transfusion reaction.
      Withholding blood products from these patients until compatible products have
      been identified is recommended. Moreover, TRALI is the leading cause of
      transfusion-related fatalities and should always be considered in transfusion
      settings. CONCLUSIONS: Suspicion for hemolytic transfusion reactions should be
      high in patients with prior allo-antibody formation; these may present as acute
      hemolysis or as a delayed hemolytic transfusion reaction. Withholding blood
      products from these patients until compatible products have been identified is
      recommended. Moreover, TRALI is the leading cause of transfusion-related
      fatalities and should always be considered in transfusion settings.

PMID- 28441943
TI  - Return to sports after plate fixation of humeral head fractures 65 cases with
      minimum 24-month follow-up.
AB  - BACKGROUND: Humeral head fractures requiring surgical intervention are severe
      injuries, which might affect the return to sports and daily activities. We
      hypothesize that athletic patients will be constrained regarding their sporting
      activities after surgically treated humeral head fractures. Despite a long
      rehabilitation program physical activities will change and an avoidance of
      overhead activities will be noticed. METHODS: Case series with 65 Patients, with
      a minimum follow-up of 24 months participated in this study. All patients were
      treated using a locking plate fixation. Their sporting activity was investigated
      at the time of the injury and re-investigated after an average of 3.83 years. The
      questionnaire setup included the evaluation of shoulder function, sporting
      activities, intensity, sport level and frequency evaluation. Level of evidence
      IV. RESULTS: At the time of injury 61 Patients (94%) were engaged in recreational
      sporting activities. The number of sporting activities declined from 26 to 23 at
      the follow-up examination. There was also a decline in sports frequency and
      duration of sports activities. CONCLUSION: The majority of patients remains
      active in their recreational sporting activity at a comparable duration and
      frequency both pre- and postoperatively. Nevertheless, shoulder centered sport
      activities including golf, water skiing and martial arts declined or were given
      up.

PMID- 28441944
TI  - Effects of unconditional cash transfers on the outcome of treatment for severe
      acute malnutrition (SAM): a cluster-randomised trial in the Democratic Republic
      of the Congo.
AB  - BACKGROUND: Cash transfer programs (CTPs) aim to strengthen financial security
      for vulnerable households. This potentially enables improvements in diet,
      hygiene, health service access and investment in food production or income
      generation. The effect of CTPs on the outcome of children already severely
      malnourished is not well delineated. The objective of this study was to test
      whether CTPs will improve the outcome of children treated for severe acute
      malnutrition (SAM) in the Democratic Republic of the Congo over 6 months.
      METHODS: We conducted a cluster-randomised controlled trial in children with
      uncomplicated SAM who received treatment according to the national protocol and
      counselling with or without a cash supplement of US$40 monthly for 6 months.
      Analyses were by intention to treat. RESULTS: The hazard ratio of reaching full
      recovery from SAM was 35% higher in the intervention group than the control group
      (adjusted hazard ratio, 1.35, 95% confidence interval (CI) = 1.10 to 1.69, P =
      0.007). The adjusted hazard ratios in the intervention group for relapse to
      moderate acute malnutrition (MAM) and SAM were 0.21 (95% CI = 0.11 to 0.41, P =
      0.001) and 0.30 (95% CI = 0.16 to 0.58, P = 0.001) respectively. Non-response and
      defaulting were lower when the households received cash. All the nutritional
      outcomes in the intervention group were significantly better than those in the
      control group. After 6 months, 80% of cash-intervened children had re-gained
      their mid-upper arm circumference measurements and weight-for-height/length Z
      scores and showed evidence of catch-up. Less than 40% of the control group had a
      fully successful outcome, with many deteriorating after discharge. There was a
      significant increase in diet diversity and food consumption scores for both
      groups from baseline; the increase was significantly greater in the intervention
      group than the control group. CONCLUSIONS: CTPs can increase recovery from SAM
      and decrease default, non-response and relapse rates during and following
      treatment. Household developmental support is critical in food insecure areas to
      maximise the efficiency of SAM treatment programs. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02460848 . Registered on 27 May 2015.

PMID- 28441945
TI  - Epidemiological investigation of Mycoplasma Synoviae in native chicken breeds in
      China.
AB  - BACKGROUD: Mycoplasma synoviae (M. synoviae) is widely distributed around the
      world, and leads to serious economic losses in the world every year.
      Nevertheless, the incidence and epidemiology of M. synoviae infection in China
      have remained unclear. RESULTS: In this study we demonstrate that over 9773
      broiler chicken flocks in 16 Chinese provinces were affected by M. synoviae
      between 2010 and 2015. Our epidemiological study revealed that M. synoviae was
      widely prevalent in multi-aged Chinese native breeder chickens, and the
      prevalence of M. synoviae in embryos of breeders reached up to 16.29%. In
      addition, our data showed that chickens aged 14 days or younger carried
      simultaneously high levels of maternal antibody against M. synoviae and high M.
      synoviae infection (10%), and low M. synoviae antibody levels in breeders and
      high proportion of M. synoviae infection in embryos could increase the chances of
      incidence in the offspring. Finally, our results also indicated that 3- to 7-week
      old chickens might be most the susceptible to M. synoviae and, therefore, might
      play a key role in the horizontal transmission of M. synoviae. CONCLUSION: Our
      findings suggest that M. synoviae is widely circulating in Chinese native
      chickens, accordingly, effective control measures are urgently needed to control
      the spread.

PMID- 28441947
TI  - Indicators of the relative availability of healthy versus unhealthy foods in
      supermarkets: a validation study.
AB  - BACKGROUND: In-store availability of healthy and unhealthy foods may influence
      consumer purchases. Methods used to measure food availability, however, vary
      widely. A simple, valid, and reliable indicator to collect comparable data on in
      store food availability is needed. METHODS: Cumulative linear shelf length of and
      variety within 22 healthy and 28 unhealthy food groups, determined based on a
      comparison of three nutrient profiling systems, were measured in 15 New Zealand
      supermarkets. Inter-rater reliability was tested in one supermarket by a second
      researcher. The construct validity of five simple indicators of relative
      availability of healthy versus unhealthy foods was assessed against this 'gold
      standard'. RESULTS: Cumulative linear shelf length was a more sensitive and
      feasible measure of food availability than variety. Four out of five shelf length
      ratio indicators were significantly associated with the gold standard (rho = 0.70
      0.75). Based on a non-significant difference from the 'gold standard' (d = 0.053
      +/- 0.040) and feasibility, the ratio of cumulative linear shelf length of fresh
      and frozen fruits and vegetables versus soft and energy drinks, crisps and
      snacks, sweet biscuits and confectionery performed best for use in New Zealand
      supermarkets. CONCLUSIONS: Four out of the five shelf length ratio indicators of
      the relative availability of healthy versus unhealthy foods in-store tested could
      be used for future research and monitoring, but additional validation studies in
      other settings and countries are recommended. Consistent use of those shelf
      length ratio indicators could enhance comparability of supermarket food
      availability between studies, and help inform policies to create healthy consumer
      food retail environments.

PMID- 28441946
TI  - The protein subunit of telomerase displays patterns of dynamic evolution and
      conservation across different metazoan taxa.
AB  - BACKGROUND: Most animals employ telomerase, which consists of a catalytic subunit
      known as the telomerase reverse transcriptase (TERT) and an RNA template, to
      maintain telomere ends. Given the importance of TERT and telomere biology in core
      metazoan life history traits, like ageing and the control of somatic cell
      proliferation, we hypothesised that TERT would have patterns of sequence and
      regulatory evolution reflecting the diverse life histories across the Animal
      Kingdom. RESULTS: We performed a complete investigation of the evolutionary
      history of TERT across animals. We show that although TERT is almost ubiquitous
      across Metazoa, it has undergone substantial sequence evolution within canonical
      motifs. Beyond the known canonical motifs, we also identify and compare regions
      that are highly variable between lineages, but show conservation within phyla.
      Recent data have highlighted the importance of alternative splice forms of TERT
      in non-canonical functions and although animals may share some conserved introns,
      we find that the selection of exons for alternative splicing appears to be highly
      variable, and regulation by alternative splicing appears to be a very dynamic
      feature of TERT evolution. We show that even within a closely related group of
      triclad flatworms, where alternative splicing of TERT was previously correlated
      with reproductive strategy, we observe highly diverse splicing patterns.
      CONCLUSIONS: Our work establishes that the evolutionary history and structural
      evolution of TERT involves previously unappreciated levels of change and the
      emergence of lineage specific motifs. The sequence conservation we describe
      within phyla suggests that these new motifs likely serve essential biological
      functions of TERT, which along with changes in splicing, underpin diverse
      functions of TERT important for animal life histories.

PMID- 28441948
TI  - Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and
      metastasis in gastric cancer.
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as critical regulators in
      a variety of human cancers, including gastric cancer (GC). However, the function
      and mechanisms responsible for these molecules in GC are not fully understood. In
      our previous study, we found that GC associated lncRNA HOXA11-AS is significantly
      upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells
      proliferation and invasion through scaffolding the chromatin modification factors
      PRC2, LSD1 and DNMT1. METHODS: HOXA11-AS expression levels in GC cells was
      detected by quantitative real-time PCR (qPCR). HOXA11-AS siRNAs and
      overexpression vector were transfected into GC cells to down-regulate or up
      regulate HOXA11-AS expression. In vitro and in vivo assays were performed to
      investigate the functional role of HOXA11-AS in GC cells cell cycle progression,
      invasion and metastasis. RIP and ChIP assays were used to determine the mechanism
      of HOXA11-AS's regulation of underlying targets. RESULTS: We found that knockdown
      of HOXA11-AS induced GC cells G0/G1 phase arrest and suppressed GC cells
      migration, invasion and metastasis in vivo. Moreover, mechanistic investigation
      showed that HOXA11-AS could interact with WDR5 and promote beta-catenin
      transcription, bind with EZH2 and repress P21 transcription, and induce KLF2 mRNA
      degradation via interacting with STAU1. CONCLUSIONS: Taken together, these
      findings show that HOXA11-AS not only could promote GC cells migration and
      invasion in vitro, but also promotes GC cells metastasis in vivo, at least in
      part, by regulating beta-catenin and KLF2.

PMID- 28441949
TI  - "It's so hard taking pills when you don't know what they're for": a qualitative
      study of patients' medicine taking behaviours and conceptualisation of medicines
      in the context of rheumatoid arthritis.
AB  - BACKGROUND: Patients with chronic illnesses are often required to take lifelong
      medication to alleviate symptoms and prevent disease progression. Many patients
      find it difficult to adhere to prescribed medication for various reasons, some of
      which may link to the way they conceptualise medicines and understand their
      illness and treatment. This study explores the medicine taking behaviours of
      patients presenting with Rheumatoid Arthritis (RA), a chronic inflammatory
      autoimmune disease. We focused particularly on patients' conceptualisation and
      understanding of medicines within this disease context, against a backdrop of
      scarce healthcare resources. METHODS: We conducted semi-structured interviews
      with 18 female patients at a rheumatology clinic in South Africa, as well as a
      review of participants' medical records. We conducted a secondary analysis of the
      data using thematic analysis and framework analysis principles. RESULTS:
      Participants reported a range of medicine taking behaviours including self
      medicating, adding complementary and alternative medicines (CAM) or traditional
      remedies, and sometimes acquiring prescribed medicines illegally. Participants
      provided insights into their understanding of what constitutes a medicine and
      what substances can be added to a prescribed regimen, which impacted on
      adherence. Importantly, the majority of participants demonstrated poor
      understanding of their illness, medications, regimens and dosage instructions.
      CONCLUSIONS: Medicine taking in the context of RA, within the studied
      demographic, is complex and appears strongly mediated by individual and
      contextual factors. Poor patient understanding, individual conceptualisation of
      medicines and medicine taking, and the availability of a range of additional
      medicines and remedies impact on adherence. Based on these findings, we make some
      suggestions for how healthcare providers can play a greater role in educating
      patients living with RA about medicines, CAM and traditional remedies, as well as
      medicine taking behaviours.

PMID- 28441950
TI  - Development of a web-based patient decision aid for initiating disease modifying
      anti-rheumatic drugs using user-centred design methods.
AB  - BACKGROUND: A main element of patient-centred care, Patient Decision Aids (PtDAs)
      facilitate shared decision-making (SDM). A recent update of the International
      Patient Decision Aids Standards (IPDAS) emphasised patient involvement during
      PtDA development, but omitted a methodology for doing so. This article reports on
      the value of user-centred design (UCD) methods for the development of a PtDA that
      aims to support inflammatory arthritis patients in their choice between disease
      modifying anti-rheumatic drugs (DMARDs). METHODS: The IPDAS development process
      model in combination with UCD methods were applied. The process was overseen by
      an eight-member multidisciplinary steering group. Patients and health
      professionals were iteratively consulted. Qualitative in-depth interviews
      combined with rapid prototyping were conducted with patients to assess their
      needs for specific functionality, content and design of the PtDA. Group meetings
      with health professionals were organized to assess patients' needs and to
      determine how the PtDA should be integrated into patient pathways. The current
      literature was reviewed to determine the clinical evidence to include in the
      PtDA. To evaluate usability among patients, they were observed using the PtDA
      while thinking aloud and then interviewed. RESULTS: The combination of patient
      interviews with rapid prototyping revealed that patients wanted to compare
      multiple DMARDs both for their clinical aspects and implications for daily life.
      Health professionals mainly wanted to refer patients to a reliable, easily
      adjustable source of information about DMARDs. A web-based PtDA was constructed
      consisting of four parts: 1) general information about SDM, inflammatory
      arthritis and DMARDs; 2) an application to compare particular DMARDs; 3) value
      clarification exercises; and 4) a printed summary of patients' notes,
      preferences, worries and questions that they could bring to discuss with their
      rheumatologist. CONCLUSIONS: The study demonstrated that UCD methods can be of
      great value for the development of PtDAs. The early, iterative involvement of
      patients and health professionals was helpful in developing a novel user-friendly
      PtDA that allowed patients to choose between DMARDs. The PtDA fits the values of
      all stakeholders and easily integrates with the patient pathway and daily
      workflow of health professionals. This collaborative designed PtDA may improve
      SDM and patient participation in arthritis care.

PMID- 28441951
TI  - Minimal clinically important difference for the 6-min walk test: literature
      review and application to Morquio A syndrome.
AB  - Morquio A syndrome is an ultra-rare, inherited lysosomal storage disorder
      associated with progressive, multi-systemic clinical impairments, causing gradual
      loss of functional capacity and endurance, impaired quality of life, and early
      mortality. Studies in Morquio A patients have used the 6-min walk test (6MWT) to
      assess functionality and endurance and to evaluate disease progression or
      efficacy of treatment. The objective of the present study was to review minimal
      clinically important differences (MCIDs) for the 6MWT reported for disease states
      that widely use the 6MWT to evaluate clinical benefit and to discuss the results
      in view of the challenges in estimating MCID for ultra-rare diseases, using the
      case of elosulfase alfa in Morquio A patients. A systematic literature search was
      performed using Embase and Medline to identify studies specifically estimating
      the MCID using either anchor-based or distribution-based methods. A total of 19
      publications on 17 studies were identified; none of these included patients with
      Morquio A syndrome or the wider disease category of lysosomal storage disorders.
      Therefore, the MCIDs determined by studies in patients with respiratory,
      cardiovascular, or musculoskeletal disease were compared to changes in the 6MWT
      seen in Morquio A patients in the pivotal phase 3 clinical trial of elosulfase
      alfa enzyme replacement therapy. The literature review showed a mean MCID for the
      6MWT of 7% change (range 3-15%) in studies using anchor-based methods and a 9%
      change (range 4-16%) using distribution-based methods. Results of the elosulfase
      alfa clinical trial and its extension showed a placebo-adjusted 14.9% improvement
      in the 6MWT from baseline at week 24, which was greater than the mean MCID based
      on the results of the systematic literature review. After 2 years, 6MWT distance
      increased by a mean of 20.7% from baseline in a modified per-protocol population,
      versus a reduction of 6.9% in comparable untreated patients from the MorCAP
      natural history study over the same period. Although further research is required
      to establish the MCID of the 6MWT in Morquio A patients, the presented data
      provide further evidence for the positive effect of elosulfase alfa in this
      patient population.

PMID- 28441952
TI  - Management of suspected primary Toxoplasma gondii infection in pregnant women in
      Norway: twenty years of experience of amniocentesis in a low-prevalence
      population.
AB  - BACKGROUND: Primary infection with Toxoplasma gondii during pregnancy may pose a
      threat to the fetus. Women infected prior to conception are unlikely to transmit
      the parasite to the fetus. If maternal serology indicates a possible primary
      infection, amniocentesis for toxoplasma PCR analysis is performed and
      antiparasitic treatment given. However, discriminating between primary and latent
      infection is challenging and unnecessary amniocenteses may occur. Procedure
      related fetal loss after amniocentesis is of concern. The aim of the present
      study was to determine whether amniocentesis is performed on the correct patients
      and whether the procedure is safe for this indication. METHODS: Retrospective
      study analysing data from all singleton pregnancies (n = 346) at Oslo University
      Hospital undergoing amniocentesis due to suspected maternal primary toxoplasma
      infection during 1993-2013. Maternal, neonatal and infant data were obtained from
      clinical hospital records, laboratory records and pregnancy charts. All serum
      samples were analysed at the Norwegian Institute of Public Health or at the
      Toxoplasma Reference Laboratory at Oslo University Hospital. The amniocenteses
      were performed at Oslo University Hospital by experienced personnel. Time of
      maternal infection was evaluated retrospectively based on serology results.
      RESULTS: 50% (173) of the women were infected before pregnancy, 23% (80) possibly
      in pregnancy and 27% (93) were certainly infected during pregnancy. Forty-nine
      (14%) women seroconverted, 42 (12%) had IgG antibody increase and 255 (74%) women
      had IgM positivity and low IgG avidity/high dye test titre. Fifteen offspring
      were infected with toxoplasma, one of them with negative PCR in the amniotic
      fluid. Median gestational age at amniocentesis was 16.7 gestational weeks (GWs)
      (Q1 = 15, Q3 = 22), with median sample volume 4 ml (Q1 = 3, Q3 = 7). Two
      miscarriages occurred 4 weeks after the procedure, both performed in GW 13. One
      of these had severe fetal toxoplasma infection. CONCLUSIONS: Half of our study
      population were infected before pregnancy. In order to reduce the unnecessary
      amniocenteses we advise confirmatory serology 3 weeks after a suspect result and
      suggest that the serology is interpreted by dedicated multidisciplinary staff.
      Amniocentesis is safe and useful as a diagnostic procedure in diagnosing
      congenital toxoplasma infection when performed after 15 GW.

PMID- 28441953
TI  - Anatomic fat depots and cardiovascular risk: a focus on the leg fat using
      nationwide surveys (KNHANES 2008-2011).
AB  - BACKGROUND: Although central fat is a well-known risk factor for cardiovascular
      disease (CVD) and cardiometabolic disorders, the effect of other regional fats or
      muscle distribution on CVD risk has not been fully investigated. METHODS: This
      was a cross-sectional study using nationally representative samples of 15,686
      subjects from the 2008-2011 Korea National Health and Nutrition Examination
      Survey. Individual CVD risk was evaluated in adults aged >=20 without prior CVD,
      using atherosclerotic cardiovascular disease (ASCVD) risk equations according to
      the 2013 ACC/AHA guidelines. Body composition was assessed by dual X-ray
      absorptiometry. RESULTS: Ratio of leg fat to total fat (LF/TF ratio) was the most
      predictive for CVD among body fat or muscle distribution parameters (AUC = 0.748,
      95% CI 0.741-0.755). ASCVD risk score was gradually increased with decreased
      LF/TF ratio (P < 0.001), and individuals whose LF/TF ratio in lowest tertile
      tended to belong to the high-risk (10-year risk >10%) group compared to those in
      the highest tertile (OR = 6.25, 95% CI 5.60-6.98). Subjects in the lowest tertile
      showed increased risk of cardiometabolic risk factor components including
      obesity, hypertension, diabetes, dyslipidemia, chronic kidney disease, and
      albuminuria (OR range 2.57-11.24, all P < 0.001). In addition, a higher LF/TF
      ratio was associated with decreased ASCVD risk, even in subjects with multiple
      CVD risk factors. Multiple logistic regression analyses also demonstrated this
      association (OR = 1.85, 95% CI 1.36-2.52). CONCLUSIONS: Among various body
      composition parameters, LF/TF ratio was superior in predicting higher CVD risk
      and a higher LF/TF ratio was independently associated with decreased risk of CVD
      and each cardiometabolic risk factor.

PMID- 28441954
TI  - Electrochemotherapy efficacy evaluation for treatment of locally advanced stage
      III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.
AB  - BACKGROUND: Extensive squamous cell carcinoma has few therapeutic options. In
      such cases, electrochemotherapy involving electroporation combined with
      antineoplastic drug appears to be a new potential option and may be considered as
      an alternative treatment. The aim of this retrospective single-center study was
      to evaluate electrochemotherapy efficacy in treatment of locally advanced stage
      III squamous cell carcinoma, in which surgical procedures would have entailed
      wide tissue sacrifice. METHODS: Clinical features, treatment response, and
      adverse effects were evaluated in 22 patients treated with electrochemotherapy
      with intravenous injection of bleomycin for extensive stage III cutaneous
      squamous cell carcinoma. Treatment of cutaneous lesions were performed according
      to the European Standard Operating Procedures of Electrochemotherapy. RESULTS:
      Overall response to electrochemotherapy treatment was observed in 18 (81.8%)
      patients. Clinical response with necrosis of tumor mass was observed from the
      first session and lasted for all follow up period that ranged between 5 and 48
      months with a median of 34 months. Overall the treatment was well tolerated with
      a very low complication rate. CONCLUSIONS: Electrochemotherapy represents a safe
      and effective therapeutic approach, associated with a good tolerability.

PMID- 28441955
TI  - Self-(in)compatibility in apricot germplasm is controlled by two major loci, S
      and M.
AB  - BACKGROUND: Apricot (Prunus armeniaca L.) exhibits a gametophytic self
      incompatibility (GSI) system and it is mostly considered as a self-incompatible
      species though numerous self-compatible exceptions occur. These are mainly linked
      to the mutated S C-haplotype carrying an insertion in the S-locus F-box gene that
      leads to a truncated protein. However, two S-locus unlinked pollen-part mutations
      (PPMs) termed m and m' have also been reported to confer self-compatibility (SC)
      in the apricot cultivars 'Canino' and 'Katy', respectively. This work was aimed
      to explore whether other additional mutations might explain SC in apricot as
      well. RESULTS: A set of 67 cultivars/accessions with different geographic origins
      were analyzed by PCR-screening of the S- and M-loci genotypes, contrasting
      results with the available phenotype data. Up to 20 S-alleles, including 3 new
      ones, were detected and sequence analysis revealed interesting synonymies and
      homonymies in particular with S-alleles found in Chinese cultivars. Haplotype
      analysis performed by genotyping and determining linkage-phases of 7 SSR markers,
      showed that the m and m' PPMs are linked to the same m 0-haplotype. Results
      indicate that m 0-haplotype is tightly associated with SC in apricot germplasm
      being quite frequent in Europe and North-America. However, its prevalence is
      lower than that for S C in terms of frequency and geographic distribution.
      Structures of 34 additional M-haplotypes were inferred and analyzed to depict
      phylogenetic relationships and M 1-2 was found to be the closest haplotype to m
      0. Genotyping results showed that four cultivars classified as self-compatible do
      not have neither the S C- nor the m 0-haplotype. CONCLUSIONS: According to
      apricot germplasm S-genotyping, a loss of genetic diversity affecting the S-locus
      has been produced probably due to crop dissemination. Genotyping and phenotyping
      data support that self-(in)compatibility in apricot relies mainly on the S- but
      also on the M-locus. Regarding this latter, we have shown that the m 0-haplotype
      associated with SC is shared by 'Canino', 'Katy' and many other cultivars. Its
      origin is still unknown but phylogenetic analysis supports that m 0 arose later
      in time than S C from a widely distributed M-haplotype. Lastly, other mutants
      putatively carrying new mutations conferring SC have also been identified
      deserving future research.

PMID- 28441957
TI  - Landscape structure affects distribution of potential disease vectors (Diptera:
      Culicidae).
AB  - BACKGROUND: Vector-pathogen dynamics are controlled by fluctuations of potential
      vector communities, such as the Culicidae. Assessment of mosquito community
      diversity and, in particular, identification of environmental parameters shaping
      these communities is therefore of key importance for the design of adequate
      surveillance approaches. In this study, we assess effects of climatic parameters
      and habitat structure on mosquito communities in eastern Austria to deliver these
      highly relevant baseline data. METHODS: Female mosquitoes were sampled twice a
      month from April to October 2014 and 2015 at 35 permanent and 23 non-permanent
      trapping sites using carbon dioxide-baited traps. Differences in spatial and
      seasonal abundance patterns of Culicidae taxa were identified using likelihood
      ratio tests; possible effects of environmental parameters on seasonal and spatial
      mosquito distribution were analysed using multivariate statistical methods. We
      assessed community responses to environmental parameters based on 14-day-average
      values that affect ontogenesis. RESULTS: Altogether 29,734 female mosquitoes were
      collected, and 21 of 42 native as well as two of four non-native mosquito species
      were reconfirmed in eastern Austria. Statistical analyses revealed significant
      differences in mosquito abundance between sampling years and provinces. Incidence
      and abundance patterns were found to be linked to 14-day mean sunshine duration,
      humidity, water-level maxima and the amount of precipitation. However, land cover
      classes were found to be the most important factor, effectively assigning both
      indigenous and non-native mosquito species to various communities, which
      responded differentially to environmental variables. CONCLUSIONS: These findings
      thus underline the significance of non-climatic variables for future mosquito
      prediction models and the necessity to consider these in mosquito surveillance
      programmes.

PMID- 28441956
TI  - What happened to anti-malarial markets after the Affordable Medicines Facility
      malaria pilot? Trends in ACT availability, price and market share from five
      African countries under continuation of the private sector co-payment mechanism.
AB  - BACKGROUND: The private sector supplies anti-malarial treatment for large
      proportions of patients in sub-Saharan Africa. Following the large-scale piloting
      of the Affordable Medicines Facility-malaria (AMFm) from 2010 to 2011, a private
      sector co-payment mechanism (CPM) provided continuation of private sector
      subsidies for quality-assured artemisinin combination therapies (QAACT). This
      article analyses for the first time the extent to which improvements in private
      sector QAACT supply and distribution observed during the AMFm were maintained or
      intensified during continuation of the CPM through 2015 in Kenya, Madagascar,
      Nigeria, Tanzania and Uganda using repeat cross-sectional outlet survey data.
      RESULTS: QAACT market share in all five countries increased during the AMFm
      period (p < 0.001). According to the data from the last ACTwatch survey round, in
      all study countries except Madagascar, AMFm levels of private sector QAACT
      availability were maintained or improved. In 2014/15, private sector QAACT
      availability was greater than 70% in Nigeria (84.3%), Kenya (70.5%), Tanzania
      (83.0%) and Uganda (77.1%), but only 11.2% in Madagascar. QAACT market share was
      maintained or improved post-AMFm in Nigeria, Tanzania and Uganda, but
      statistically significant declines were observed in Kenya and Madagascar. In
      2014/5, QAACT market share was highest in Kenya and Uganda (48.2 and 47.5%,
      respectively) followed by Tanzania (39.2%), Nigeria (35.0%), and Madagascar
      (7.0%). Four of the five countries experienced significant decreases in median
      QAACT price during the AMFm period. Private sector QAACT prices were maintained
      or further reduced in Tanzania, Nigeria and Uganda, but prices increased
      significantly in Kenya and Madagascar. SP prices were consistently lower than
      those of QAACT in the AMFm period, with the exception of Kenya and Tanzania in
      2011, where they were equal. In 2014/5 QAACT remained two to three times more
      expensive than the most popular non-artemisinin therapy in all countries except
      Tanzania. CONCLUSIONS: Results suggest that a private sector co-payment mechanism
      for QAACT implemented at national scale for 5 years was associated with positive
      and sustained improvements in QAACT availability, price and market share in
      Nigeria, Tanzania and Uganda, with more mixed results in Kenya, and few
      improvements in Madagascar. The subsidy mechanism as implemented over time across
      countries was not sufficient on its own to achieve optimal QAACT uptake.
      Supporting interventions to address continued availability and distribution of
      non-artemisinin therapies, and to create demand for QAACT among providers and
      consumers need to be effectively implemented to realize the full potential of
      this subsidy mechanism. Furthermore, there is need for comprehensive market
      assessments to identify contemporary market barriers to high coverage with both
      confirmatory testing and appropriate treatment.

PMID- 28441958
TI  - Metformin to Augment Strength Training Effective Response in Seniors (MASTERS):
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Muscle mass and strength are strong determinants of a person's
      quality of life and functional independence with advancing age. While resistance
      training is the most effective intervention to combat age-associated muscle
      atrophy (sarcopenia), the ability of older adults to increase muscle mass and
      strength in response to training is blunted and highly variable. Thus, finding
      novel ways to complement resistance training to improve muscle response and
      ultimately quality of life among older individuals is critical. The purpose of
      this study is to determine whether a commonly prescribed medication called
      metformin can be repurposed to improve the response to resistance exercise
      training by altering the muscle tissue inflammatory environment. METHODS/DESIGN:
      Individuals aged 65 and older are participating in a two-site, randomized, double
      blind, placebo-controlled trial testing the effects of metformin or placebo on
      muscle size, strength, and physical function when combined with a progressive
      resistance training program. Participants consume 1700 mg of metformin per day or
      placebo for 2 weeks before engaging in a 14-week progressive resistance training
      regimen, with continued metformin or placebo. Participants are then monitored
      post-training to determine if the group taking metformin derived greater overall
      benefit from training in terms of muscle mass and strength gains than those on
      placebo. Muscle biopsies are taken from the vastus lateralis at three time points
      to assess individual cellular and molecular adaptations to resistance training
      and also changes in response to metformin. DISCUSSION: The response of aged
      muscles to a resistance training program does not always result in a positive
      outcome; some individuals even experience a loss in muscle mass following
      resistance training. Thus, adjuvant therapies, including pharmacological ones,
      are required to optimize response to training in those who do not respond and may
      be at increased risk of frailty. This is the first known metformin repurposing
      trial in non-diseased individuals, aimed specifically at the resistance exercise
      "non-responder" phenotype present in the aging population. The overall goal of
      this trial is to determine if combined exercise-metformin intervention therapy
      will benefit older individuals by promoting muscle hypertrophy and strength
      gains, thereby maintaining functional independence. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02308228 . Registered on 25 November 2014.

PMID- 28441959
TI  - Serological measures to assess the efficacy of malaria control programme on Ambae
      Island, Vanuatu.
AB  - BACKGROUND: Seroepidemiology can provide evidence for temporal changes in malaria
      transmission and is an important tool to evaluate the effectiveness of control
      interventions. During the early 2000s, Vanuatu experienced an acute increase in
      malaria incidence due to a lapse in funding for vector control. After the
      distribution of subsidised insecticide-treated nets (ITNs) resumed in 2003,
      malaria incidence decreased in the subsequent years. This study was conducted to
      find the serological evidence supporting the impact of ITN on exposure to
      Anopheles vector bites and parasite prevalence. METHODS: On Ambae Island, blood
      samples were collected from 231 and 282 individuals in 2003 and 2007,
      respectively. Parasite prevalence was determined by microscopy. Antibodies to
      three Plasmodium falciparum (PfSE, PfMSP-119, and PfAMA-1) and three Plasmodium
      vivax (PvSE, PvMSP-119, and PvAMA-1) antigens, as well as the Anopheles-specific
      salivary antigen gSG6, were detected by ELISA. Age-specific seroprevalence was
      analysed using a reverse catalytic modelling approach to estimate seroconversion
      rates (SCRs). RESULTS: Parasite rate decreased significantly (P < 0.001) from
      19.0% in 2003 to 3.2% in 2007, with a shift from P. falciparum predominance to P.
      falciparum-P. vivax co-dominance. Significant (P < 0.001) decreases were observed
      in seroprevalence to all three P. falciparum antigens but only two of three P.
      vivax antigens (except PvAMA-1; P = 0.153), consistent with the more pronounced
      decrease in P. falciparum prevalence. Seroprevalence to gSG6 also decreased
      significantly (P < 0.001), suggesting that reduced exposure to vector bites was
      important to the decrease in parasite prevalence between 2003 and 2007. Analyses
      of age-specific seroprevalence showed a three-fold decrease in P. falciparum
      transmission, but the evidence for the decrease in P. vivax transmission was less
      clear. CONCLUSIONS: Serological markers pointed to the effectiveness of ITNs in
      reducing malaria prevalence on Ambae Island between 2003 and 2007. The
      recombinant gSG6 antigen originally developed to indicate exposure to the
      Afrotropical vector An. gambiae may be used in the Pacific to complement the
      traditional measure of entomological inoculation rate (EIR).

PMID- 28441960
TI  - Incorporating assessment of the cervical facet joints in the modified Stoke
      ankylosing spondylitis spine score is of additional value in the evaluation of
      spinal radiographic outcome in ankylosing spondylitis.
AB  - BACKGROUND: To aim was to investigate the additional value of incorporating the
      de Vlam cervical facet joint score in the modified ankylosing spondylitis (AS)
      spine score (mSASSS) for the evaluation of spinal radiographic outcome in AS.
      METHOD: Baseline and 4-year radiographs from 98 consecutive patients from the
      Groningen Leeuwarden AS (GLAS) cohort, who had AS treated with TNF-alpha
      inhibitors, were scored by two readers; the vertebral bodies were assessed
      according to the mSASSS (0-72) and cervical facet joints (C2-C7) were assessed
      according to the method of de Vlam (0-15). The combined AS spine score (CASSS)
      was calculated as the sum of both total scores (range 0-87) and compared with the
      original mSASSS according to three aspects of the Outcome Measures in
      Rheumatology Clinical Trials (OMERACT) filter: feasibility, discrimination, and
      truth. RESULTS: Feasibility: the CASSS was calculated in 91% of the patients. No
      additional radiographs were necessary and the assessment took only a few extra
      minutes. Discrimination: both scoring methods had excellent inter-observer
      reliability (intra-class correlation coefficient (ICC) status scores >0.99,
      progression scores 0.92). Incorporating the cervical facet joints did not result
      in an increase in measurement error. The CASSS detected more patients with
      definite damage (61% vs. 57%) and definite progression (55% vs. 48%). Truth:
      higher CASSS scores at baseline and higher progression scores were seen in 41
      (46%) and 22 (25%) patients, respectively. Cervical rotation correlated better
      with cervical CASSS than with cervical mSASSS (Spearman's rho = 0.68 vs. 0.59).
      CONCLUSIONS: The CASSS is a relevant and easy modification of the mSASSS. It
      captures more patients with AS who have spinal radiographic damage and
      progression, which is of great additional value in the evaluation of radiographic
      outcome in this heterogeneous and overall slowly progressing disease.

PMID- 28441961
TI  - The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers
      of Alzheimer's pathology.
AB  - BACKGROUND: Insulin resistance (IR) has previously been associated with an
      increased risk of developing Alzheimer's disease (AD), although the relationship
      between IR and AD is not yet clear. Here, we examined the influence of IR on AD
      using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in
      cognitively healthy men. We also aimed to characterise the shared protein
      signatures between IR and AD. METHODS: Fifty-eight cognitively healthy men, 28 IR
      and 30 non-IR (age and APOE epsilon4 matched), were drawn from the Metabolic
      Syndrome in Men study in Kuopio, Finland. CSF AD biomarkers (amyloid beta-peptide
      (Abeta), total tau and tau phosphorylated at the Thr181 epitope) were examined
      with respect to IR. Targeted proteomics using ELISA and Luminex xMAP assays were
      performed to assess the influence of IR on previously identified CSF and plasma
      protein biomarker candidates of AD pathology. Furthermore, CSF and plasma
      SOMAscan was performed to discover proteins that associate with IR and CSF AD
      biomarkers. RESULTS: CSF AD biomarkers did not differ between IR and non-IR
      groups, although plasma insulin correlated with CSF Abeta/tau across the whole
      cohort. In total, 200 CSF and 487 plasma proteins were differentially expressed
      between IR and non-IR subjects, and significantly enriched pathways, many of
      which have been previously implicated in AD, were identified. CSF and plasma
      proteins significantly associated with CSF AD biomarkers were also discovered,
      and those sensitive to both IR and AD were identified. CONCLUSIONS: These data
      indicate that IR is not directly related to the level of CSF AD pathology in
      cognitively healthy men. Proteins that associated with both AD and IR are
      potential markers indicative of shared pathology.

PMID- 28441962
TI  - Acceptability of a mobile health intervention to enhance HIV care coordination
      for patients with substance use disorders.
AB  - BACKGROUND: Persons living with HIV and substance use disorders face barriers to
      sustained engagement in medical care, leading to suboptimal antiretroviral
      treatment outcomes. Innovative mobile technology tools such as customizable
      smartphone applications have the potential to enhance existing care coordination
      programs, but have not been rigorously studied. METHODS: We developed and
      implemented a two-component intervention consisting of peer health navigation
      supported by a smartphone application conducting ecologic momentary assessment
      (EMA) of barriers to care and medication adherence. Patients with a history of
      antiretroviral treatment failure and substance use were recruited to participate
      in the 9-month pilot intervention. Three peer health navigators were trained to
      provide social and logistical support while participants re-engaged in HIV care.
      We assessed the acceptability of the intervention components using qualitative
      analysis of in-depth interviews conducted with study participants and peer
      navigators. RESULTS: Of 19 patients enrolled in the study, 17 participated for at
      least 2 months and 15 completed the entire 9-month study protocol. The
      acceptability of the peer navigation intervention was rated favorably by all
      participants interviewed, who felt that peer support was instrumental in helping
      them re-engage in HIV care. Participants also responded favorably to the
      smartphone application, but described its usefulness mostly as providing
      reminders to take medications and attend appointments, rather than as a
      facilitator of patient navigation. CONCLUSIONS: Peer health navigation and
      smartphone-based EMA are acceptable approaches to facilitating engagement in HIV
      care for drug using populations. Future studies to evaluate the efficacy of this
      approach for improving long-term retention in care and antiretroviral treatment
      outcomes are warranted. ClinicalTrials.gov Identifier NCT01941108; registered on
      September 4, 2013.

PMID- 28441963
TI  - In-hospital airway management training for non-anesthesiologist EMS physicians: a
      descriptive quality control study.
AB  - BACKGROUND: Pre-hospital airway management is a major challenge for emergency
      medical service (EMS) personnel. Despite convincing evidence that the rescuer's
      qualifications determine efficacy of tracheal intubation, in-hospital airway
      management training is not mandatory in Austria, and often neglected. Thus we
      sought to prove that airway management competence of EMS physicians can be
      established and maintained by a tailored training program. METHODS: In this
      descriptive quality control study we retrospectively evaluated all in- and pre
      hospital airway cases managed by EMS physicians who underwent a structured in
      hospital training program in anesthesia at General Hospital Wiener Neustadt. Data
      was obtained from electronic anesthesia and EMS documentation systems. RESULTS:
      From 2006 to 2016, 32 EMS physicians with 3-year post-graduate education, but
      without any prior experience in anesthesia were trained. Airway management
      proficiency was imparted in three steps: initial training, followed by an ongoing
      practice schedule in the operating room (OR). Median and interquartile range of
      number of in-hospital tracheal intubations (TIs) vs. use of supra-glottic airway
      devices (SGA) were 33.5 (27.5-42.5) vs. 19.0 (15.0-27.0) during initial training;
      62.0 (41.8-86.5) vs. 33.5 (18.0-54.5) during the first, and 64.0 (34.5-93.8) vs.
      27 (12.5-56.0) during the second year. Pre-hospitaly, every physician performed
      9.0 (5.0-14.8) TIs vs. 0.0 (0.0-0.0) SGA cases during the first, and 9.0 (7.0
      13.8) TIs vs. 0.0 (0.0-0.3) SGA during the second year. Use of an SGA was
      mandatory when TI failed after the second attempt, thus accounting for a total of
      33 cases. In 8 cases, both TI and SGA failed, but bag mask ventilation was
      successfully performed. No critical events related to airway management were
      noted and overall success rate for TI with a max of 2 attempts was 95.3%.
      DISCUSSION: Number of TIs per EMS physician is low in the pre-hospital setting. A
      training concept that assures an additional 6 0+ TIs per year appears to minimize
      failure rates. Thus, a fixed amount of working days in anesthesia seems crucial
      to maintain proficiency.  CONCLUSIONS: In-hospital training programs are
      mandatory for non-anesthetist EMS physicians to gain competence in airway
      management and e mergency anest hesia.Our results might be helpful when
      discussing the need for regulation and financing with the authorities.

PMID- 28441964
TI  - Fecal metagenomic profiles in subgroups of patients with myalgic
      encephalomyelitis/chronic fatigue syndrome.
AB  - BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is
      characterized by unexplained persistent fatigue, commonly accompanied by
      cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever,
      lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the
      gastrointestinal microbiome and peripheral inflammation are associated with
      ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal
      bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients
      and 50 healthy controls frequency-matched for age, sex, race/ethnicity,
      geographic site, and season of sampling. RESULTS: Topological analysis revealed
      associations between IBS co-morbidity, body mass index, fecal bacterial
      composition, and bacterial metabolic pathways but not plasma immune molecules.
      IBS co-morbidity was the strongest driving factor in the separation of
      topological networks based on bacterial profiles and metabolic pathways.
      Predictive selection models based on bacterial profiles supported findings from
      topological analyses indicating that ME/CFS subgroups, defined by IBS status,
      could be distinguished from control subjects with high predictive accuracy.
      Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa
      associated with ME/CFS patients without IBS. Increased abundance of unclassified
      Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS
      with IBS; while increased unclassified Bacteroides abundance and decreased
      Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite
      findings of differences in bacterial taxa and metabolic pathways defining ME/CFS
      subgroups, decreased metabolic pathways associated with unsaturated fatty acid
      biosynthesis and increased atrazine degradation pathways were independent of IBS
      co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine
      ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS
      as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity
      measures including pain, fatigue, and reduced motivation were correlated with the
      abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS:
      Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial
      metabolic disturbances that may influence disease severity. However, our findings
      indicate that dysbiotic features that are uniquely ME/CFS-associated may be
      masked by disturbances arising from the high prevalence of IBS co-morbidity in
      ME/CFS. These insights may enable more accurate diagnosis and lead to insights
      that inform the development of specific therapeutic strategies in ME/CFS
      subgroups.

PMID- 28441965
TI  - Evaluation of a DNA Abeta42 vaccine in adult rhesus monkeys (Macaca mulatta):
      antibody kinetics and immune profile after intradermal immunization with full
      length DNA Abeta42 trimer.
AB  - BACKGROUND: Aggregated amyloid-beta peptide 1-42 (Abeta42), derived from the
      cellular amyloid precursor protein, is one of the pathological hallmarks of
      Alzheimer's disease (AD). Although active immunization against Abeta42 peptide
      was successful in AD mouse models and led to removal of plaques and improved
      memory, a similar clinical trial in humans (Abeta42 peptide immunization with QS
      21 adjuvant) was stopped in phase II, when 6% of the treated patients developed
      encephalitis. Currently ongoing passive immunizations with the injection of
      preformed monoclonal antibodies against different epitopes within the Abeta1-42
      peptide, which do not lead to activation of the immune system, have shown some
      effects in slowing AD pathology. Active DNA Abeta42 immunizations administered
      with the gene gun into the skin are noninflammatory because they activate a
      different T-cell population (Th2) with different cytokine responses eliciting a
      different humoral immune response. We present our findings in rhesus macaques
      that underwent the DNA Abeta42 immunization via gene gun delivery into the skin.
      METHODS: Six rhesus monkeys received two different doses of a DNA Abeta42 trimer
      vaccine. The humoral immune response was analyzed from blood throughout the
      study, and cellular immune responses were determined in peripheral blood
      mononuclear cells (PBMCs) after three and six immunizations. RESULTS: DNA Abeta42
      trimer immunization led to high titer antibody responses in the nonhuman primate
      (NHP) model. Antibodies generated in the rhesus monkeys following DNA Abeta42
      immunization detected amyloid plaques consisting of human Abeta42 peptide in the
      brain of the triple-transgenic AD mouse model. T-cell responses showed no
      interferon (IFN)-gamma- and interleukin (IL)-17-producing cells from PBMCs in
      Enzyme-Linked ImmunoSpot assays after three immunization time points. At six
      immunization time points, IFN-gamma- and IL-17-producing cells were found in
      immunized animals as well as in control animals and were thus considered
      nonspecific and not due to the immunization regimen. IFN-gamma and IL-17
      secretion in response to Abeta42 peptide restimulation became undetectable after
      a 3-month rest period. CONCLUSIONS: Intradermal DNA Abeta42 immunization
      delivered with the gene gun produces a high antibody response in NHPs and is
      highly likely to be effective and safe in a clinical AD prevention trial in
      patients.

PMID- 28441966
TI  - Maintenance tegafur-uracil versus observation following an adjuvant oxaliplatin
      based regimen in patients with stage III colon cancer after radical resection:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: We conducted a prospective randomized study of an adjuvant
      oxaliplatin-based regimen plus orally administered tegafur-uracil in patients
      with stage III colon cancer after radical resection to evaluate the feasibility
      of this drug combination in cancer clinical outcomes, acute toxicity, disease
      free survival (DFS), and overall survival (OS) in Taiwan. METHODS/DESIGN: This is
      an open-label, randomized, comparative, double-arm, multicenter, phase III study
      to assess DFS, OS, and safety profiles of the aforementioned drug combination as
      maintenance therapy for 1 year in patients with stage III colon cancer after
      radical resection in Taiwan. Following the completion of an adjuvant oxaliplatin
      based regimen for 3 weeks with no evident disease recurrence, all eligible
      patients will be randomly assigned to either arm A (maintenance therapy) or arm B
      (observation arm) in a 2:1 ratio (364 and 182 patients in the tegafur-uracil and
      observation groups, respectively). Treatment in arm A will be started within 7
      days of randomization. If the patients reported disease recurrence, intolerable
      toxicity, withdrew consent or the investigator determined that the patient should
      be withdrawn during the study period, they were withdrawn from the study. If a
      patient was discontinued from the study, the corresponding data were not reused,
      and the patient was not allowed to re-enter the study. DISCUSSION: A unique
      characteristic of this intervention was that the adjuvant chemotherapy with
      oxaliplatin and tegafur-uracil was anticipated to be safe and has high treatment
      efficacy, with the advantage of yielding a favorable response rate and tolerable
      toxicity profile. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02836977
      . Registered on 18 July 2016.

PMID- 28441968
TI  - Anaemia control and the interpretation of biochemical tests for iron status in
      children.
AB  - BACKGROUND: Anaemia is one of the world's most prevalent child health problems.
      Its control in Africa and other developing nations has been hindered by
      uncertainty regarding its cause. Anaemia control has been particularly
      problematic in regions where the non-iron deficiency causes of anaemia, are
      projected to be substantial. The implementation of effective interventions to
      reduce the anaemia prevalence, requires improved documentation on iron status and
      other causes of anaemia for target populations. METHODS: This cross-sectional
      study enrolled n = 184 children, aged 6-8 years from Kwazulu-Natal, South Africa.
      Tests of haemoglobin, serum ferritin, soluble transferrin receptor and C-reactive
      protein were performed. These conventional measures of iron status were used to
      calculate body iron and to categorize the children into different groups of
      anaemia profiles. RESULTS: Anaemia prevalence was high, 43/184 (23.4%). Iron
      deficiency anaemia contributed 7/43 (16.3%) to the anaemia prevalence compared to
      non-iron deficiency anaemia 34/43 (79.1%) and mixed anaemia 2/43 (4.7%). In total
      47/184 (25.5%) of the sampled children had either iron deficiency or anaemia.
      Information about the presence of inflammation was used to adjust serum ferritin
      concentrations, resulting in improved diagnosis of iron deficiency. CONCLUSION:
      Appropriate investigations for iron status and inflammation/infection screening,
      need to be integral in the evaluation of anaemia and its causes before anaemia
      control interventions are implemented. Interventions that target the
      multifactorial nature of anaemia in school-aged children need to be strengthened.
      Additionally, regular screening of anaemia in school-aged children from
      disadvantaged communities is recommended.

PMID- 28441967
TI  - Comparison of CSF markers and semi-quantitative amyloid PET in Alzheimer's
      disease diagnosis and in cognitive impairment prognosis using the ADNI-2
      database.
AB  - BACKGROUND: The relative performance of semi-quantitative amyloid positron
      emission tomography (PET) and cerebrospinal fluid (CSF) markers in diagnosing
      Alzheimer's disease (AD) and predicting the cognitive evolution of patients with
      mild cognitive impairment (MCI) is still debated. METHODS: Subjects from the
      Alzheimer's Disease Neuroimaging Initiative 2 with complete baseline cognitive
      assessment (Mini Mental State Examination, Clinical Dementia Rating [CDR] and
      Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-cog] scores), CSF
      collection (amyloid-beta1-42 [Abeta], tau and phosphorylated tau) and 18F
      florbetapir scans were included in our cross-sectional cohort. Among these,
      patients with MCI or substantial memory complaints constituted our longitudinal
      cohort and were followed for 30 +/- 16 months. PET amyloid deposition was
      quantified using relative retention indices (standardised uptake value ratio
      [SUVr]) with respect to pontine, cerebellar and composite reference regions.
      Diagnostic and prognostic performance based on PET and CSF was evaluated using
      ROC analysis, multivariate linear regression and survival analysis with the Cox
      proportional hazards model. RESULTS: The cross-sectional study included 677
      participants and revealed that pontine and composite SUVr values were better
      classifiers (AUC 0.88, diagnostic accuracy 85%) than CSF markers (AUC 0.83 and
      0.85, accuracy 80% and 75%, for Abeta and tau, respectively). SUVr was a strong
      independent determinant of cognition in multivariate regression, whereas Abeta
      was not; tau was also a determinant, but to a lesser degree. Among the 396
      patients from the longitudinal study, 82 (21%) converted to AD within 22 +/- 13
      months. Optimal SUVr thresholds to differentiate AD converters were quite similar
      to those of the cross-sectional study. Composite SUVr was the best AD classifier
      (AUC 0.86, sensitivity 88%, specificity 81%). In multivariate regression,
      baseline cognition (CDR and ADAS-cog) was the main predictor of subsequent
      cognitive decline. Pontine and composite SUVr were moderate but independent
      predictors of final status and CDR/ADAS-cog progression rate, whereas baseline
      CSF markers had a marginal influence. The adjusted HRs for AD conversion were 3.8
      (p = 0.01) for PET profile, 1.2 (p = ns) for Abeta profile and 1.8 (p = 0.03) for
      tau profile. CONCLUSIONS: Semi-quantitative amyloid PET appears more powerful
      than CSF markers for AD grading and MCI prognosis in terms of cognitive decline
      and AD conversion.

PMID- 28441969
TI  - Molecular identification of Plasmodium spp. and blood meal sources of anophelines
      in environmental reserves on Sao Luis Island, state of Maranhao, Brazil.
AB  - BACKGROUND: Considering the diversity of feeding habits that females of some
      species of anophelines present, it is important to understand which vertebrates
      are part of blood food sources and how important is the role of each in the
      ecoepidemiology of malaria. There are many vector species for Plasmodium spp. in
      the State of Maranhao, Brazil. In Sao Luis Island, Anopheles aquasalis is the
      main vector for human malaria; this species is abundant in areas with primates
      that are positive for Plasmodium. Anopheles aquasalis has natural exophilic and
      zoophilic feeding behavior, but in cases of high density and absence of animals,
      presents quite varied behavior, and feeds on human blood. In this context, the
      objective of the present study was to identify Plasmodium spp. and the blood meal
      sources of anophelines in two environmental reserves on Sao Luis Island, state of
      Maranhao, using molecular methods. METHODS: Between June and July 2013, female
      anophelines were collected in the Sitio Aguahy Private Reserve, in the
      municipality of Sao Jose de Ribamar, and in the Sitio Mangalho Reserve, located
      within the Maracana Environmental Protection Area, in the municipality of Sao
      Luis. CDC-type light traps, Shannon traps and protected human bait were used
      during three consecutive hours in peridomestic and wooded areas. Pools of
      anophelines were formed using mosquitoes of the same species that had been caught
      at the same site on the same date. A genus-specific amplification protocol based
      on the 18S rRNA gene was used for qPCR and cPCR. RESULTS: A total of 416
      anophelines were collected, of the following species: An. aquasalis (399), An.
      mediopunctatus (3), An. shannoni (1), An. nuneztovari (sensu lato) (1), An.
      goeldii (1), An. evansae (2) and An. (Nyssorhynchus) sp. (9), comprising 54
      pools. Two pools were positive for Plasmodium (2/54) based on the 18S rRNA gene.
      In the phylogenetic analysis using the maximum likelihood method, based on a 240
      bp fragment of the 18S rRNA gene, it was found that the sequences of Plasmodium
      sp. amplified from pools of An. aquasalis (pool 2) and An. nuneztovari (s.l.)
      (pool 10) were phylogenetically related to a clade of P. falciparum isolates from
      India, and to a clade of Plasmodium sp. isolates from psittacines in Brazil,
      respectively. Cat, dog and human DNA were identified in the blood meals of the
      anophelines sampled. CONCLUSION: The species An. aquasalis was the most abundant
      anopheline species in Sao Luis Island. Plasmodium spp. DNA was detected, thus
      confirming the importance of this species as the main vector on Sao Luis Island,
      Brazil. In addition, the presence of An. nuneztovari (s.l.) with DNA positive for
      Plasmodium spp. confirms its importance as a secondary vector.

PMID- 28441970
TI  - Salidroside contributes to reducing blood pressure and alleviating
      cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition
      of L-type calcium channel in smooth muscle cells.
AB  - BACKGROUND: Vascular disease is a common and often severe complication in
      diabetes mellitus. Hyperglycemia and hypertension are considered to be two of the
      leading risk factors for vascular complications in diabetic patients. However,
      few pharmacologic agents could provide a combinational therapy for controlling
      hyperglycemia and blood pressure in diabetic patients at the same time.
      Salidroside (SAL) is the major active ingredient derived from Rhodiola. Recently,
      it has been reported that SAL have an obvious hypoglycemic effect in diabetes and
      show a beneficial activity in diabetic vascular dysfunction. However, it remains
      unknown whether or not SAL treatment could directly reduce blood pressure in
      diabetes. Furthermore, it is not clear what is the molecular mechanism underlying
      the vascular protection of SAL treatment in diabetes. METHODS: Male diabetic Goto
      Kakizaki (GK) and non-diabetic control Wistar-Kyoto (WKY) rats were administrated
      with different dosages of SAL (50, 100 and 200 mg/kg/day) for 4 weeks.
      Contractile responsiveness of cerebral artery to KCl or 5-HT was investigated by
      Pressure Myograph System. The activity of CaL channel was investigated by
      recording whole-cell currents, assessing the expressions of CaL channel alpha1C
      subunit and its downstream kinase, MLCK, at protein or mRNA levels. RESULTS: We
      showed that administration of 100 mg/kg/day SAL for 4 weeks not only lowered
      blood glucose, but also reduced blood pressure and alleviated cerebrovascular
      contractile activity in diabetic GK rats, which suggested that SAL treatment may
      provide a combinational therapy for lowering blood glucose and reducing blood
      pressure in diabetes at the same time. Furthermore, SAL treatment markedly
      inhibited the function and expression of CaL channel in cerebral VSMCs isolated
      from diabetic GK rats or when exposed to hyperglycemia condition, which may be
      the underlying mechanism responsible for the vascular protection of SAL in
      diabetes. CONCLUSIONS: The present study provided evidences that SAL contributes
      to reducing blood pressure and alleviating cerebrovascular contractile activity
      in diabetic GK rats by inhibition of CaL channel in smooth muscle cells, which
      may provide a novel approach to treat vascular complications in diabetic
      patients.

PMID- 28441971
TI  - The clinical and cost-effectiveness of stratified care for patients with
      sciatica: the SCOPiC randomised controlled trial protocol (ISRCTN75449581).
AB  - BACKGROUND: Sciatica has a substantial impact on patients, and is associated with
      high healthcare and societal costs. Although there is variation in the clinical
      management of sciatica, the current model of care usually involves an initial
      period of 'wait and see' for most patients, with simple measures of advice and
      analgesia, followed by conservative and/or more invasive interventions if
      symptoms fail to resolve. A model of care is needed that does not over-treat
      those with a good prognosis yet identifies patients who do need more intensive
      treatment to help with symptoms, and return to everyday function including work.
      The aim of the SCOPiC trial (SCiatica Outcomes in Primary Care) is to establish
      whether stratified care based on subgrouping using a combination of prognostic
      and clinical information, with matched care pathways, is more effective than non
      stratified care, for improving time to symptom resolution in patients consulting
      with sciatica in primary care. We will also assess the impact of stratified care
      on service delivery and evaluate its cost-effectiveness compared to non
      stratified care. METHODS/DESIGN: Multicentre, pragmatic, parallel arm randomised
      trial, with internal pilot, cost-effectiveness analysis and embedded qualitative
      study. We will recruit 470 adult patients with sciatica from general practices in
      England and Wales, over 24 months. Patients will be randomised to stratified care
      or non-stratified care, and treated in physiotherapy and spinal specialist
      services, in participating NHS services. The primary outcome is time to first
      resolution of sciatica symptoms, measured on a 6-point ordered categorical scale,
      collected using text messaging. Secondary outcomes include physical function,
      pain intensity, quality of life, work loss, healthcare use and satisfaction with
      treatment, and will be collected using postal questionnaires at 4 and 12-month
      follow-up. Semi-structured qualitative interviews with a subsample of
      participants and clinicians will explore the acceptability of stratified care.
      DISCUSSION: This paper presents the details of the rationale, design and
      processes of the SCOPiC trial. Results from this trial will contribute to the
      evidence base for management of patients with sciatica consulting in primary
      care. TRIAL REGISTRATION: ISRCTN75449581 , date: 20.11.2014.

PMID- 28441972
TI  - Efficacy of olmesartan amlodipine in Colombian hypertensive patients (soat
      study).
AB  - BACKGROUND: Emerging evidence has shown a significant deficit in the control of
      hypertension (blood pressure <140/90 mmHg) among Hispanics or Latinos in about
      65%. This study aims to determine the efficacy of the combination in fixed doses
      of olmesartan and amlodipine (20/5, 40/5, and 40/10 mg) in hypertensive patients
      treated in daily clinical practice by Colombian doctors. METHODS: This was an
      observational, retrospective, open-label, multi-center, non-comparative study.
      The primary outcome was a change in systolic and diastolic blood pressure from
      the baseline to week 12; the secondary outcome was the proportion of patients
      achieving a target blood pressure of <140/90 mmHg. Safety and tolerability were
      also evaluated. For analysis, a student t test was used for paired data, McNemar
      test, and ANCOVA. RESULTS: A total of 428 patients were enrolled from 16 centers
      in Colombia. At 12 weeks, patients' systolic blood pressure decreased in response
      to all three doses: by 27.75 +/- 20.73 mmHg in 20/5 mg, 31.13 +/- 22.23 mmHg in
      40/5 mg, and 46.96 +/- 20.15 mmHg in 40/10 mg (all p < 0.001). Furthermore, the
      diastolic blood pressure decreased by 14.19 +/- 12.89 mmHg in 20/5 mg, 16.25 +/-
      10.87 mmHg in 40/5 mg, and 24.83 +/- 10.41 mmHg in 40/10 mg (all p < 0.001). The
      percentage of patients achieving target blood pressure was 71.31% in 20/5 mg,
      70.16% in 40/5 mg, and 63.33% in 40/10 mg. CONCLUSIONS: This study demonstrates
      the efficacy of the combination in fixed doses of olmesartan and amlodipine in
      the treatment of Colombian hypertensive patients.

PMID- 28441973
TI  - Treatment-limiting decisions in patients with severe traumatic brain injury in a
      Norwegian regional trauma center.
AB  - BACKGROUND: Treatment-limiting decisions (TLD) for severe traumatic brain injury
      (sTBI) have been sparsely studied. This study determine prevalence, main reason
      for, categories and timing of TLDs in a Norwegian regional trauma setting.
      METHODS: A retrospective study of a 2-year cohort of 579 sTBI patients admitted
      to Oslo University Hospital (OUH). Prospectively collected data in the OUH Trauma
      Registry were combined with retrospective data from a chart review regarding
      TLDs. RESULTS: TLDs were documented for 101/579 sTBI patients (17%). The
      situation was evaluated as futile in 59 cases and as potentially inappropriate in
      42 cases. The three most frequent types of TLDs were withholding of neurosurgery,
      do not resuscitate orders and withdrawing of organ support. In 70% of cases, the
      first TLD was made within 2 days after injury, while in 14%, the first TLD was
      made later than day 7. Twenty percent (20/101) of the first TLDs were later
      adjusted, revoked in 4 patients and broadening of TLDs in 16 patients. The median
      time from the decision to death was 2 days (range 1-652). TLDs were documented in
      93% of in-hospital death cases (n = 79). In-hospital deaths occurred in 73% of
      TLD group cases and 1% of non-TLD group cases. Family interaction and multi-team
      discussions were documented in >88% of cases, but no advanced directives were
      found, and notifications of patients' preferences were found in only 7% of cases.
      DISCUSSION: Clinicians should consider limiting treatment if continued treatment
      is not in the patients best interest. A range of different types of TLDs were
      applied for patients after sTBI in the trauma hospital setting. CONCLUSION: TLDs
      were found in 17% of sTBI patients. Value considerations behind TLDs in this care
      context need to be further explored.

PMID- 28441974
TI  - Evaluating effectiveness and cost-effectiveness of a group psychological
      intervention using cognitive behavioural strategies for women with common mental
      disorders in conflict-affected rural Pakistan: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: The impact of humanitarian disasters upon mental health is well
      recognised. The evidence for psychological interventions for mental health is
      mounting, but few interventions have been rigorously tested in humanitarian
      settings. To be sustainable in humanitarian settings interventions need to be
      short, simple, deliverable by nonspecialists under supervision, and adopt a
      transdiagnostic approach where an array of mental health outcomes are addressed
      simultaneously. These elements have been incorporated into the newly developed
      WHO Problem Management Plus (PM+) Group intervention. The aim of this trial is to
      evaluate the locally adapted PM+ Group intervention for women in Swat, Pakistan.
      METHODS: This PM+ Group trial is a two-arm, single-blind, cluster randomised
      controlled trial conducted in a community-based setting with women in rural
      Pakistan. PM+ is delivered in partnership with the Lady Health Worker (LHW)
      Programme which provides community-based health care to women in Pakistan. Thirty
      four LHW clusters will be randomised in a 1:1 allocation ratio using a permuted
      block randomisation method. Participants screened and found to meet the inclusion
      criteria will be allocated to either the PM+ intervention group (n = 306), or the
      control arm (n = 306). The manualised PM+ intervention involves five sessions,
      each lasting 3 h, and introduces four strategies applied by participants to
      problems that they are facing. It is delivered by local female facilitators with
      a minimum of 16 years of education who are provided with targeted training and
      supervision. The primary outcome is individual psychological distress, measured
      by levels of anxiety and depression on the Hospital Anxiety and Depression Scale
      at 20 weeks after baseline. Secondary outcomes include major depression, post
      traumatic stress disorder, levels of social support, levels of functioning, and
      economic effectiveness. Intervention acceptability will be explored through an
      embedded qualitative study. DISCUSSION: The PM+ Group trial will provide
      important evidence on the effectiveness of an empirically supported psychological
      treatment delivered by nonspecialists in a humanitarian setting. If proven
      effective, the qualitative component will inform strategies for PM+ Group scale
      up in health systems in other humanitarian settings. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry, identifier: ACTRN12616000037404.
      Registered on 19 January 2016; WHO Protocol ID RPC705, v.4, 2 November 2015.

PMID- 28441976
TI  - Diversity or disarray? A systematic review of decision-making capacity for
      treatment and research in schizophrenia and other non-affective psychoses.
AB  - BACKGROUND: Valid consent for treatment or research participation requires that
      an individual has decision-making capacity (DMC), which is the ability to make a
      specific decision. There is evidence that the psychopathology of schizophrenia
      can compromise DMC. The objective of this review was to examine the presence or
      absence of DMC in schizophrenia and the socio-demographic/psychopathological
      factors associated. METHODS: We searched three databases Embase, Ovid MEDLINE(R),
      and PsycINFO for studies reporting data on the proportion of DMC for treatment
      and research (DMC-T and DMC-R), and/or socio-demographic/psychopathological
      associations with ability to make such decisions, in people with schizophrenia
      and related illnesses. RESULTS: A total of 40 studies were identified. While high
      levels of heterogeneity limited direct comparison, meta-analysis of inpatient
      data showed that DMC-T was present in 48% of people. Insight was strongly
      associated with DMC-T. Neurocognitive deficits were strongly associated with lack
      of DMC-R and to a lesser extent DMC-T. With the exception of years of education,
      there was no evidence for an association with socio-demographic factors.
      CONCLUSIONS: Insight and neurocognitive deficits are most closely associated with
      DMC in schizophrenia. The lack of an association with socio-demographic factors
      dispels common misperceptions regarding DMC and characteristics such as age.
      Although our results reveal a wide spectrum of DMC-T and DMC-R in schizophrenia,
      this could be partly due to the complexity of the DMC construct and the
      heterogeneity of existing studies. To facilitate systematic review research,
      there is a need for improvement within research study design and increased
      consistency of concepts and tools.

PMID- 28441975
TI  - Seek, test, treat: substance-using women in the HIV treatment cascade in South
      Africa.
AB  - BACKGROUND: Women in South Africa who use alcohol and other drugs face multiple
      barriers to HIV care. These barriers make it difficult for women to progress
      through each step in the HIV treatment cascade from diagnosis to treatment
      initiation and adherence. This paper examines correlates of HIV status, newly
      diagnosed HIV status, and use of antiretroviral therapy (ART). METHODS: Outreach
      workers recruited sexually active Black African women who used substances in
      Pretoria as part of a U.S. National Institutes of Health-funded geographically
      clustered randomized trial examining the effect of an intervention to reduce
      alcohol and drug use as well as sexual risk behaviors. To address the question of
      interest in the current investigation, cross-sectional baseline data were used.
      At study enrollment, all participants (N = 641) completed an interview, and
      underwent rapid HIV testing and biological drug screening. Those who tested
      positive for HIV and were eligible for ART were asked about their barriers to
      initiating or adhering to ART. Bivariate and multivariable logistic regression
      analyses were conducted to determine correlates of HIV status, newly diagnosed
      HIV, and ART use. RESULTS: At enrollment, 55% of participants tested positive for
      HIV, and 36% of these women were newly diagnosed. In multivariable analyses of
      the entire sample, women who had completed 10th grade were less likely to be
      living with HIV (OR 0.69; CI 0.48, 0.99) and those from the inner city were more
      likely to be living with HIV (OR 1.83; CI 1.26, 2.67). Among HIV-positive
      participants, women were less likely to be newly diagnosed if they had ever been
      in substance abuse treatment (OR 0.15; CI 0.03, 0.69) or used a condom at last
      sex (OR 0.58; CI 0.34, 0.98) and more likely to be newly diagnosed if they were
      physically assaulted in the past year (OR 1.97; CI 1.01, 3.84). Among women
      eligible for ART, fewer were likely to be on treatment (by self-report) if they
      had a positive urine test for opiates or cocaine (OR 0.27; CI 0.09, 0.80).
      CONCLUSIONS: These results, although cross-sectional, provide some guidance for
      provincial authorities to address barriers to HIV care for sexually active,
      substance-using vulnerable women in Pretoria. Targeting the inner city with
      prevention campaigns, expanding and improving substance abuse treatment programs,
      linking clients with simultaneous HIV testing and treatment, and targeting women
      who have experienced sexual assault and violence may help the government achieve
      the UNAIDS 90-90-90 treatment target. Clinical Trials.gov NCT01497405 registered
      on December 1, 2011.

PMID- 28441977
TI  - Detecting Clusters in Atom Probe Data with Gaussian Mixture Models.
AB  - Accurately identifying and extracting clusters from atom probe tomography (APT)
      reconstructions is extremely challenging, yet critical to many applications.
      Currently, the most prevalent approach to detect clusters is the maximum
      separation method, a heuristic that relies heavily upon parameters manually
      chosen by the user. In this work, a new clustering algorithm, Gaussian mixture
      model Expectation Maximization Algorithm (GEMA), was developed. GEMA utilizes a
      Gaussian mixture model to probabilistically distinguish clusters from random
      fluctuations in the matrix. This machine learning approach maximizes the data
      likelihood via expectation maximization: given atomic positions, the algorithm
      learns the position, size, and width of each cluster. A key advantage of GEMA is
      that atoms are probabilistically assigned to clusters, thus reflecting
      scientifically meaningful uncertainty regarding atoms located near
      precipitate/matrix interfaces. GEMA outperforms the maximum separation method in
      cluster detection accuracy when applied to several realistically simulated data
      sets. Lastly, GEMA was successfully applied to real APT data.

PMID- 28441978
TI  - Comparing the Consistency of Atom Probe Tomography Measurements of Small-Scale
      Segregation and Clustering Between the LEAP 3000 and LEAP 5000 Instruments.
AB  - The local electrode atom probe (LEAP) has become the primary instrument used for
      atom probe tomography measurements. Recent advances in detector and laser design,
      together with updated hit detection algorithms, have been incorporated into the
      latest LEAP 5000 instrument, but the implications of these changes on
      measurements, particularly the size and chemistry of small clusters and elemental
      segregations, have not been explored. In this study, we compare data sets from a
      variety of materials with small-scale chemical heterogeneity using both a LEAP
      3000 instrument with 37% detector efficiency and a 532-nm green laser and a new
      LEAP 5000 instrument with a manufacturer estimated increase to 52% detector
      efficiency, and a 355-nm ultraviolet laser. In general, it was found that the
      number of atoms within small clusters or surface segregation increased in the
      LEAP 5000, as would be expected by the reported increase in detector efficiency
      from the LEAP 3000 architecture, but subtle differences in chemistry were
      observed which are attributed to changes in the way multiple hit detection is
      calculated using the LEAP 5000.

PMID- 28441979
TI  - Can a better patients' phenotyping predict the efficacy of tiotropium in
      symptomatic asthma?

PMID- 28441980
TI  - Reply.

PMID- 28441981
TI  - Vitamin D and food allergies in children: A systematic review and meta-analysis.
AB  - BACKGROUND: Vitamin D insufficiency has been associated with immune dysfunction
      and linked to the epidemic of atopic diseases in the Western hemisphere, yet
      there are studies with conflicting results, and the risk has not been quantified
      uniformly across studies. OBJECTIVE: To perform a systematic review and meta
      analysis to evaluate and quantify if vitamin D deficiency is associated with the
      presence and persistence of food allergy. METHODS: A systematic review was
      undertaken to assess for the association between food allergy and vitamin D
      status in children. RESULTS: A total of 368 citations relevant to this systematic
      review were identified. In the whole review, 5105 children were included. We did
      not find a significant association between 25 hydroxy vitamin D (25(OH)D) status
      and risk of food allergy in children (odds ratio [OR] 1.35 [95% confidence
      interval {CI}, 0.79-2.29]; p = 0.27, I2 = 58.3%). We conducted subgroup analyses
      based on different cutoffs of the 25(OH)D status (20 versus 30 ng/mL). Only one
      study used 30 ng/mL and found that children with <30 ng/mL were more likely to
      report food allergy than children with a 25(OH)D status of >=30 ng/mL (OR 2.04
      [95% CI, 1.02-4.04]; p = 0.04). Four studies compared children with a 25(OH)D
      status of <20 ng/mL to children with a 25(OH)D status of >=20 ng/mL and found no
      significant differences (OR 1.18 [95% CI, 0.62-2.27]; p = 0.62, I2 = 62.7%).
      CONCLUSION: Based on the studies analyzed, this systematic review did not
      identify a significant association between vitamin D status and food allergy.
      Interpretation of the included studies was limited by a lack of a standard
      definition for vitamin D deficiency and insufficient knowledge regarding the
      optimal vitamin D status needed to impact immune function. Longitudinal studies
      are warranted to assess if vitamin D might contribute to the development of food
      allergy.

PMID- 28441982
TI  - 25-Hydroxyvitamin D, biomarkers of eosinophilic inflammation, and airway
      remodeling in children with newly diagnosed untreated asthma.
AB  - BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) and asthma development may be
      related to airway remodeling and eosinophilia. Periostin is proposed as a key
      molecule that links remodeling and eosinophilic inflammation. OBJECTIVE: We
      evaluated the association of 25(OH)D concentration with periostin, peripheral
      blood eosinophil counts, and immunoglobulin E (IgE) in children with newly
      diagnosed asthma. METHODS: The study included 150 children: 110 with atopic
      asthma and 40 constituted a reference group. Fasting blood was collected for cell
      counts and serum for measurements of 25(OH)D, periostin, IgE, and C-reactive
      protein (CRP) concentrations. RESULTS: Significantly lower 25(OH)D, elevated IgE
      concentrations, and eosinophil counts were found in children with asthma compared
      with the reference group (p = 0.0001). A lower forced expiratory volume in the
      first second of expiration percentage predicted value was associated with a lower
      25(OH)D value in children with asthma. The bronchodilator reversibility was
      inversely related to serum 25(OH)D concentrations (R = -0.45, p = 0.029). The
      children with asthma and with a 25(OH)D deficient concentration (<=20 ng/mL) had
      higher concentrations of periostin (p = 0.035) and CRP (p = 0.01) than those with
      a sufficient 25(OH)D concentration (>=30 ng/L). Additional analysis revealed
      statistically significant differences (p = 0.013) when comparing periostin
      concentrations between subjects with a 25(OH)D deficient concentration (<=20
      ng/mL) and subjects who did not have a deficient concentration (>20 ng/mL). In
      individuals with asthma, a 25(OH)D concentration of <30 ng/mL had no impact on
      eosinophilia, whereas IgE concentrations were associated with increased
      eosinophils, and the effect of periostin on eosinophilia was small although
      significant. Multivariate regression, including 25(OH)D concentration, CRP level,
      eosinophil counts, and sex, accounted for 7% of periostin variation in subjects
      with asthma. CONCLUSION: In newly diagnosed pediatric asthma, 25(OH)D
      concentrations revealed a small although significant association with periostin
      levels but no effect on eosinophilia. A low vitamin D concentration may increase
      airway remodeling induced by inflammatory mediators, but further clinical studies
      aimed to explain the causal link between vitamin D insufficiency and asthma are
      needed.

PMID- 28441983
TI  - Association between depression and asthma in Korean adults.
AB  - PURPOSE: Asthma is a one of the most common allergic diseases, and depression is
      an important comorbidity with asthma. However, little is known about the
      prevalence of depression in Korean adults with asthma. This study was performed
      to find the association between asthma and depression in Korean adults and to
      investigate the demographic and socioeconomic characteristics in Korean adults
      with asthma and with depression. METHODS: Data were acquired from 47,351 men and
      women, ages >19 years, who participated in the Korea National Health and
      Nutrition Examination Survey, which was conducted from 2007 to 2014. The presence
      of asthma and depression was based on self-reported physician diagnosis in the
      Health Interview Surveys. RESULTS: The prevalence of asthma was 2.8% and of
      depression was 4.1%. Logistic regression analysis showed that single marital
      status (separated or divorced) (adjusted odds ratio [aOR] 1.291 [95% confidence
      interval {CI}, 1.077-1.547]), unemployment (aOR 1.226 [95% CI, 1.061-1.417]),
      under middle school graduated education level (aOR 2.433 [95% CI, 1.867-3.171]),
      middle school graduated education level (aOR 1.759 [95% CI, 1.330-2.327]),
      obesity (aOR 1.403 [95% CI, 1.196-1.647]), and depression (aOR 1.796 [95% CI,
      1.422-2.267]) were significantly associated with adult asthma; however, sex, age,
      monthly family income, residential area, smoking status, hypertension, and
      diabetes mellitus were not associated with adult asthma. Compared with
      individuals without asthma and with depression, patients with asthma and with
      depression were prone to be single (separated or divorced) and to have a lower
      education level (p < 0.01) Conclusion: The present study showed that depression
      was associated with asthma in Korean adults.

PMID- 28441984
TI  - Asthma control in Saudi Arabia: Gender implications.
AB  - BACKGROUND: Gender-related factors in asthma control should be considered in
      clinical consultations to substantially improve asthma control in women.
      Meanwhile, a limited number of studies have been reported on gender differences
      in factors related to asthma control, especially in Saudi Arabia. OBJECTIVE: To
      study the potential gender differences in factors associated with asthma control
      among adult patients with physician-diagnosed asthma. METHODS: A cross-sectional
      study was conducted in adult patients with asthma who attended primary care
      clinics at three major hospitals in Riyadh, Saudi Arabia. Asthma control was
      measured by using the Asthma Control Test. Asthma control status was classified
      as either controlled (Asthma Control Test score of >19) or uncontrolled (Asthma
      Control Test score of <=19). Multiple logistic regression analysis was performed.
      RESULTS: In this study, 58.9% of men and 77.0% of women had uncontrolled asthma
      (p = 0.002). Factors associated with uncontrolled asthma were different between
      men and women, except for household income. Reporting higher levels of stress
      (odds ratio [OR] 4.3 [95% confidence interval {CI}, 1.7-11.1]), daily tobacco
      smoking (OR 5.8 [95% CI, 1.5-23.5]), and a monthly household income of <15,000
      Saudi Arabian Riyals (OR 4.5 [95% CI, 1.9-10.5]) were associated with
      uncontrolled asthma in men. Being unemployed (OR 3.4 [95% CI, 1.3-9.4]), being
      obese (OR 3.2 [95% CI, 1.1-9.2]), or having a monthly household income of <15,000
      Saudi Arabian Riyals (OR 3.1 [95% CI, 1.2-8.0]) were associated with uncontrolled
      asthma in women. CONCLUSION: This study demonstrated that many factors, such as
      stress, occupation, and obesity, had a differential relationship with
      uncontrolled asthma among men and women in Saudi Arabia that could provide more
      insight into methods of improving asthma control, especially in women.

PMID- 28441986
TI  - Medical therapy versus dietary avoidance in eosinophilic esophagitis: Which
      approach is better?
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic immune-mediated
      esophageal disease characterized by esophageal symptoms and esophageal
      eosinophilia. It is induced by food triggers and by environmental allergens in
      some patients. No U.S. Food and Drug Administration approved therapies exist for
      patients with EoE. Common therapies include topical corticosteroids (TCS) and
      dietary restriction. METHODS: This article reviewed the pros and cons of a
      medical versus dietary approach in treating EoE in children and adults. Available
      data on short- and long-term efficacy, ease of implementation, cost, adverse
      effects, and quality of life (QoL) were summarized. RESULTS: Although no
      comparative studies of TCS versus dietary restrictions exist, they seemed to be
      equivalent from an efficacy standpoint. However, each therapy offers different
      advantages and disadvantages. TCS allow ingestion of multiple food triggers and
      improve QoL of patients with EoE. However, TCS have the potential for topical
      and/or systemic adverse effects and can be costly in the long run. Dietary
      restriction therapies allow identification of food triggers and are less costly
      in the long run. However, they are more challenging to implement because they
      require a team approach with a dietitian and an allergist. In addition, they
      decrease the QoL of some children with EoE, often require extensive allergy
      testing and multiple endoscopies, and are not effective when environmental
      allergens trigger EoE. Therefore, the choice of medical versus dietary therapy
      needs to be individualized based on a thorough medical evaluation and discussion
      with patients with EoE and their families. CONCLUSION: Research is needed to
      establish the lowest most effective and safe dose of TCS and the extent of
      adherence needed when eliminating foods for EoE, and to find less-invasive ways
      to monitor histologic disease activity. Potential results from this research may
      allow more tailored therapies or specific combination therapies that would take
      advantage of each treatment modality to maximize benefits to the patient while
      maintaining disease remission.

PMID- 28441985
TI  - Atopy, asthma, and the elderly: A paradigm for personalized therapy.

PMID- 28441987
TI  - Hypersensitivity to biomedical implants: Prevention and diagnosis.
AB  - BACKGROUND: There has been growing interest in the potential for adverse
      immunologic reactions to metals in biomedical devices and increasing referrals
      for the evaluation and management of metal hypersensitivity reactions reported in
      orthopedic, cardiac, gynecologic, and dental implant devices. However, there are
      few studies that give evidence-based recommendations on how to evaluate this
      issue in our practices. METHODS: We reviewed reasonable evidence and expert
      opinion on biomedical device hypersensitivity and published guidelines on pre-
      and postimplantation evaluation of delayed hypersensitivity reactions in patients
      suspected of possible metal hypersensitivity to biomedical devices. RESULTS:
      There is consensus that routine preimplantation evaluation in individuals with no
      history of adverse cutaneous reactions to metals or a history of implant-related
      adverse events is not necessary. However, patients with a history of metal
      hypersensitivity of a magnitude sufficient to cause concern for the patient or
      health care provider may benefit from evaluation by patch testing (PT) before
      device implantation. Patients after implantation and with chronic unexplained
      implant failure or with dermatitis may benefit from patch test evaluation after
      other causes, such as infection and biomechanical issues, are ruled out. However,
      a positive metal patch test result does not prove symptom causality, and the
      decision regarding implant revision can only be made after a thorough discussion
      among the patient, the allergist or dermatologist, and the orthopedic surgeon.
      CONCLUSION: Consensus guidelines for the evaluation of hypersensitivity to
      biomedical devices can be used by the practicing physician while awaiting for the
      results of further investigations.

PMID- 28441988
TI  - Asthma pathogenesis, diagnosis, and management in the elderly.
AB  - BACKGROUND: Due to the aging population, there is an increase in the number of
      elderly patients with asthma. Although signs and symptoms are similar to those in
      younger patients, diagnosis can be challenging due to presence of coexisting
      conditions in this population. OBJECTIVES: The purpose of this review was to
      highlight the challenges with regards to diagnosis, management, the high rates of
      medical costs and mortality in elderly asthmatics. METHODS AND RESULTS:
      Scientific literature regarding asthma in the elderly population was reviewed.
      When compared to younger patients, elderly asthmatics have different drug
      responses, higher rates of bronchial hyper reactivity, more severe phenotype, and
      lower prevalence of atopy. In addition, there are issues with the adverse effects
      of asthma medications, use of proper inhaler technique and compliance.
      CONCLUSION: There is an unmet need for research in elderly patients with asthma,
      specifically to facilitate diagnosis, and to investigate therapeutic strategies
      to improve quality of life in this population.

PMID- 28441989
TI  - Ara h2 levels in dust from homes of individuals with peanut allergy and
      individuals with peanut tolerance.
AB  - BACKGROUND: Approximately 1% of the U.S. population has a peanut allergy.
      Previous studies that measured peanut protein in house dust support the
      hypothesis that household peanut consumption may lead to clinical sensitization
      through transdermal exposure. OBJECTIVE: The aim of this pilot study was to
      characterize Ara h2 levels in house dust from homes with and without individuals
      with peanut allergy. METHODS: Household dust was obtained from homes with an
      individual with peanut allergy and from homes with no individual with peanut
      allergy. Ara h2 levels were determined by using a monoclonal antibody-based
      immunoassay with a level of determination of 150 ng per gram of dust. Peanut
      consumption information was obtained by questionnaire. RESULTS: A total of 85
      dust samples were collected: 38 from homes with a individual with peanut allergy
      and 47 from control homes. The median Ara h2 level in homes with an individual
      with peanut allergy was 1236 ng/g (interquartile range [IQR], 256-1342 ng/g),
      whereas the median Ara h2 level in homes without an individual with peanut
      allergy was 650 ng/g (IQR, 163-2201 ng/g). Ara h2 levels in dust from homes of
      individuals with peanut allergy were not significantly lower than in dust from
      control homes. Of the homes with an individual with peanut allergy, 15 reported
      complete avoidance of peanut in the home (39%). Ara h2 levels in homes that
      completely avoided peanuts were not significantly lower than Ara h2 levels in
      homes that did not restrict peanuts (p = 0.531). CONCLUSION: Although families
      may restrict peanuts and peanut products in the home, there was still detectable
      Ara h2 levels found in homes. Each subject's definition of restriction may vary,
      there seemed to be peanut protein entering the home, although the protein origin
      is not known. Possibilities include cross-reactivity with another antigen or
      transport into the home on some vector. Further investigation of hypotheses
      regarding cross-reactivity and environmental exposure to Ara h2 is necessary.

PMID- 28441990
TI  - High mobility group box 1: Biomarker of inhaled corticosteroid treatment response
      in children with moderate-severe asthma.
AB  - BACKGROUND: High mobility group box 1 (HMGB1) is abnormally expressed in serum
      and sputum of patients with allergic asthma. OBJECTIVE: The aim of this study was
      to investigate the role of HMGB1 as guidance for treatment management of children
      with asthma. METHODS: Thirty children with asthma and 44 healthy children were
      enrolled. The patients were classified according to Global Initiative for Asthma
      Guideline disease severity criteria. Sputum HMGB1 levels and lung function index
      (percentage forced expiratory volume in 1 second [FEV1%]) were recorded in the
      cohort study at baseline (T0) and after 3 (T3) and 6 (T6) months of inhaled
      corticosteroids (ICS) treatment. RESULTS: Sputum HMGB1 levels were significantly
      higher in all the patients with asthma (p < 0.001). An inverse correlation
      between sputum HMGB1 levels and pulmonary function parameters was observed only
      in the children with moderate asthma (T0: FEV1%, r = -0.9891, p < 0.001; T3:
      FEV1%, r = -0.6763, p < 0.001; T6: FEV1%, r = -0.5419, p < 0.05) and in the
      children with severe asthma (T0: FEV1%, r = -0.8696, p < 0.001; T3: FEV1%, r = 
      0.6477, p < 0.05; T6: FEV1%, r = -0.8627, p < 0.001). After ICS treatment, a
      significant decrease of sputum HMGB1 levels was noted in moderate (T0 [93.44 +/-
      20.65 ng/mL] versus T3 [77.96 +/- 1.81 ng/mL] versus T6 [67.75 +/- 3.01 ng/mL]; p
      < 0.0001) and in the children with severe asthma (T0 [130.3 +/- 7.48 ng/mL]
      versus T3 [156.9 +/- 1.09 ng/mL] versus T6 [116.08 +/- 4.77 ng/mL]; p < 0.0001)
      data are mean +/- standard deviation, respectively. The area under the receiver
      operating characteristic curve, performed to define the diagnostic profile of
      sputum HMGB1 levels in identifying the children with asthma, was 0.713.
      CONCLUSION: In addition to the findings that HMGB1 is a sensitive biomarker of
      allergic asthma in children, our data demonstrated a significant correlation
      between the decrease of HMGB1 levels and a successful treatment response.

PMID- 28441991
TI  - In vitro impact of anti-immunoglobulin E monoclonal antibodies, including
      omalizumab on whole blood basophil histamine release: Assessment of direct
      induction of basophil histamine release and evaluation of modulation of allergen
      induced basophil histamine release.
AB  - AIM: The aim of this study was to evaluate the potential of anti-immunoglobulin E
      (IgE) and/or anti-IgE-IgE immune complexes to release histamine from peripheral
      blood basophils. In addition, a potential modulating effect of anti-IgE-IgE
      complexes on allergen-induced peripheral blood basophil histamine release was
      evaluated. METHODS: Whole blood basophil histamine release (WBB-HR) tests done by
      using glass-fiber-based microtiter plates were performed in 62 patients with
      allergic rhinitis and/or asthma sensitized to perennial allergens. Evaluation of
      the direct effects of monoclonal anti-IgEs, including E25, E27, and QGE031, on
      WBB-HR, and the indirect effects of anti-IgE-serum IgE complexes on spontaneous
      and allergen-induced WBB-HR were conducted. The tests were performed with and
      without pretreatment of the basophils with interleukin 3, and the results were
      expressed as the fraction of total histamine content released. RESULTS: There was
      no difference between WBB-HR induced by any of the studied anti-IgE antibodies
      and that induced by isotype antibodies for all blood samples assessed, which, for
      each patient, was significantly less than that induced by positive anti-IgE
      control antibodies. Similarly, no effect of any of the studied anti-IgE-IgE
      complexes on spontaneous or allergen-induced WBB-HR could be demonstrated.
      CONCLUSION: There was no evidence that humanized, monoclonal anti-IgE antibodies
      E25 (omalizumab), E27, or QGE031 directly or indirectly induced histamine release
      from peripheral blood basophils.

PMID- 28441992
TI  - Safety of a C1-inhibitor concentrate in pregnant women with hereditary
      angioedema.
AB  - BACKGROUND: Increased estrogen levels during pregnancy can exacerbate hereditary
      angioedema (HAE), yet disease and treatment ramifications remain poorly studied
      in pregnant women. OBJECTIVE: Data from the international Berinert Patient
      Registry were used to evaluate outcomes of pregnancies exposed to plasma-derived,
      pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH) during routine HAE
      management. METHODS: This observational registry, conducted between 2010 and 2014
      at 30 U.S. and 7 European sites, gathered data on 318 subjects and 15,000 pnfC1
      INH infusions. Whenever possible, the subjects who used pnfC1-INH during
      pregnancy were followed up to term to assess neonatal outcomes and to collect
      maternal adverse events (AE) that occurred up to 1 month after pnfC1-INH
      administration. RESULTS: The registry data base included 11 pregnancies in 10
      subjects who used pnfC1-INH for HAE attack treatment and/or prophylaxis (>261
      doses during pregnancy). Eight pregnancies concluded in the birth of a healthy
      baby. Of the remaining three pregnancies: one was voluntarily terminated at 9
      weeks of gestation; a second ended as a first-trimester spontaneous abortion 1
      week after the subject's most recent pnfC1-INH infusion and was considered
      unrelated to pnf-C1INH treatment; and the third occurred in a subject who exited
      the registry approximately 2 months before her due date, with no further follow
      up. As assessed for 30 days after each pnfC1-INH infusion, there were no AEs that
      were considered related to pnfC1-INH therapy. CONCLUSION: Administration of pnfC1
      INH during pregnancy was generally safe and not associated with any treatment
      related AEs. In all registry pregnancies followed up to term, the birth of a
      healthy baby was reported.

PMID- 28441993
TI  - Randomized, placebo-controlled study of cetirizine and loratadine in children
      with seasonal allergic rhinitis.
AB  - BACKGROUND: Pharmacologic treatment is a mainstay of allergy therapy and many
      caregivers use over-the-counter antihistamines for the treatment of seasonal
      allergic rhinitis (SAR) symptoms in children. OBJECTIVE: To assess the efficacy
      and safety of cetirizine 10 mg syrup versus loratadine 10 mg syrup versus placebo
      syrup in a randomized double-blind study of children, ages 6-11 years, with SAR.
      METHODS: This randomized, double-blind, parallel-group, placebo-controlled study
      was conducted at 71 U.S. centers during the spring tree and grass pollen season.
      After a 1-week placebo run-in period, qualified subjects were randomized to once
      daily cetirizine 10 mg (n = 231), loratadine 10 mg (n = 221), and placebo (n =
      231) for 2 weeks. The primary efficacy end point was change from baseline in the
      subject's mean reflective total symptom severity complex (TSSC) score over 14
      days. RESULTS: Children treated with cetirizine experienced significantly greater
      TSSC score reductions versus children treated with placebo over 14 days (least
      square mean change, -2.1 versus -1.6; p = 0.006). The differences in TSSC score
      improvement over 14 days between the cetirizine versus loratadine groups (-2.1
      versus -1.8; p = 0.124) and between the loratadine versus placebo groups (-1.8
      versus -1.6; p = 0.230) were not statistically significant. Predominant adverse
      events in the cetirizine, loratadine, and placebo groups were headache (3.5, 3.6,
      and 3.1%, respectively) and pharyngitis (3.5, 2.7, and 3.5%, respectively).
      Somnolence was reported in three subjects (1.3%) treated with cetirizine and in
      none of the other subjects. CONCLUSION: Cetirizine 10 mg was statistically
      significantly more efficacious than placebo in the treatment of SAR symptoms in
      children ages 6-11 years. Symptom improvement was not significantly different
      between the loratadine 10 mg and placebo groups.

PMID- 28441994
TI  - A 30-year-old woman with chronic hives, intermittent fevers, and joint pain.
AB  - Chronic urticaria with concomitant systemic symptoms may be seen in several
      rheumatologic and autoinflammatory conditions. Although most of these conditions
      tend to improve with corticosteroids, symptoms often recur with dose tapering.
      The appearance of the rash in addition to the symptom pattern and laboratory data
      must be considered to differentiate potential causes. We presented a unique case
      of chronic urticaria with fevers and arthralgias. A diagnosis was made, and the
      patient had rapid improvement with targeted therapy.

PMID- 28441995
TI  - For the Patient.

PMID- 28442002
TI  - N2O Emission and Hydroxylamine Oxidase (HAO) Activity in a Nitrogen Removal
      Process Based on Activated Sludge with Three COD/NH4+ Ratios.
AB  - This study dealt with nitrous oxide (N2O) emission and hydroxylamine oxidase
      (HAO) activity of waste sludge in a nitrification and denitrification process
      employing three carbon nitrogen (C/N) ratios in a sequencing batch reactor (SBR).
      The experimental results indicated that N2O emission increased dramatically after
      the C/N ratio in the sludge increased from 6.5 to 9.3, which was greater than the
      N2O emission at two other C/N ratios (3.5, 6.5). The HAO activity in the anoxic
      period was higher with all three C/N ratios than in the aerobic period. The
      results suggest that N2O was produced primarily in the aerobic period and the
      main source of the N2O emission resulted from denitrification by nitrifying
      bacteria and aerobic hydroxylamine oxidation. When a relatively deficient carbon
      source existed, the N2O emission under anoxic conditions was affected by the HAO
      activity and vice versa. When the HAO activity was relatively high, it was found
      that more N2O was released.

PMID- 28442003
TI  - Lipid Production for Biodiesel from Sludge and Crude Glycerol.
AB  - Oleaginous yeast Trichosporon oleaginosus was studied for lipid production
      using municipal sludge with or without fortification of crude glycerol in a 15-L
      fermenter. The maximum lipid content (concentration) was 32.0% w/w (9.35 g/L),
      33.6% (10.13 g/L), 33.3% (9.13 g/L), and 33.1% (9.03 g/L) w/w with the addition
      of 25, 50, 100, and 150 g/L glycerol, respectively. Glycerol concentration had
      little effect on lipid accumulation. However, glycerol concentration
      substantially affected increase of biomass concentration and cell count. The
      suitable glycerol concentration was approximately 40 g/L for Trichosporon
      oleaginosus growing in sludge medium with initial suspended solids (SS)
      concentration 30 g/L. Addition of nitrogen to sludge-glycerol medium enhanced
      lipid and biomass concentration. The energy conversion efficiency was 1.78, 1.55,
      and 1.71 with no nitrogen added, with addition of 1 g/L urea, and 3.7 g/L
      peptone, respectively. The biodiesel production cost was estimated nearly 0.75
      US$/L.

PMID- 28442004
TI  - Multi-Response Optimization of Process Parameters for Imidacloprid Removal by
      Reverse Osmosis Using Taguchi Design.
AB  - In this study, a multi-response optimization method using Taguchi's robust
      design approach is proposed for imidacloprid removal by reverse osmosis. Tests
      were conducted with different membrane type (BW30, LFC-3, CPA-3), transmembrane
      pressure (TMP = 20, 25, 30 bar), volume reduction factor (VRF = 2, 3, 4), and pH
      (3, 7, 11). Quality and quantity of permeate are optimized with the multi
      response characteristics of the total dissolved solid (TDS), conductivity,
      imidacloprid, and total organic carbon (TOC) rejection ratios and flux of
      permeate. The optimized conditions were determined as membrane type of BW30, TMP
      30 bar, VRF 3, and pH 11. Under these conditions, TDS, conductivity,
      imidacloprid, and TOC rejections and permeate flux were 97.50 97.41, 97.80,
      98.00% and 30.60 L/m2.h, respectively. Membrane type was obtained as the most
      effective factor; its contribution is 64%. The difference between the predicted
      and observed value of multi-response signal/noise (MRSN) is within the confidence
      interval.

PMID- 28442005
TI  - Implications of Using Different Water Sources When Hydrologically Compacting
      Bioretention Columns.
AB  - Many investigators have conducted research on bioretention systems both in the
      laboratory and field. There is little consensus on which sources of water are
      best suited to hydrologically compact bioretention columns. Water with low ionic
      strength can leach ions from soil media, resulting in a different soil chemistry
      environment than would be found in typical bioretention applications. Soil
      columns were hydrologically compacted with three different water sources often
      used in column studies: deionized water, tap water, and rain water. Influent and
      effluent samples for each water source were measured for pH, conductivity,
      copper, zinc, and phosphate. On average, deionized water yielded larger
      percentage increases between influent and effluent for pH, conductivity, copper,
      and zinc, indicating that deionized water leaches out more ions from bioretention
      media than tap water or rain water. To maintain soil chemistry similar to the
      field, rain water or tap water should be used in column studies.

PMID- 28442006
TI  - Meta-Modeling-Based Groundwater Remediation Optimization under Flexibility in
      Environmental Standard.
AB  - This study develops a meta-modeling based mathematical programming approach
      with flexibility in environmental standards. It integrates numerical simulation,
      meta-modeling analysis, and fuzzy programming within a general framework. A set
      of models between remediation strategies and remediation performance can well
      guarantee the mitigation in computational efforts in the simulation and
      optimization process. In order to prevent the occurrence of over-optimistic and
      pessimistic optimization strategies, a high satisfaction level resulting from the
      implementation of a flexible standard can indicate the degree to which the
      environmental standard is satisfied. The proposed approach is applied to a
      naphthalene-contaminated site in China. Results show that a longer remediation
      period corresponds to a lower total pumping rate and a stringent risk standard
      implies a high total pumping rate. The wells located near or in the down-gradient
      direction to the contaminant sources have the most significant efficiency among
      all of remediation schemes.

PMID- 28442007
TI  - Evaluation of B. cereus MTCC 25641 for the Treatment of Dairy Waste Effluent.
AB  - Dairy is one of the industries producing wastewater rich in organic matter and
      thus leading to creation of odorous and high COD containing effluent.
      Biotreatment leading to bioconversion of the waste materials is probably the most
      cost-effective technique for managing and utilizing waste. A pilot-scale aerobic
      treatment plant showing air pressure of 6 kg/cm3 was designed keeping all the
      conditions similar to the main aerobic plant of any dairy plant. The COD
      (Chemical Oxygen Demand) of the control effluent i.e., without aeration,
      decreased from 588.5 mg/L on the first day to 147.75 mg/L on the seventh day
      while the effluent inoculated with B. cereus MTCC 25641 decreased the COD load
      from 588.5 mg/L on the first day to 38.75 mg/L on the seventh day, which shows
      that a pilot plant B. cereus MTCC 25641 showed excellent results as 50.68% COD
      and 44.07% BOD (Biochemical Oxygen Demand) reduction, while pH increased from 6.7
      to 8.54 along with 44.06% increase in TDS (Total Dissolved solids) was seen after
      24h of aeration.

PMID- 28442008
TI  - Biotransformation of RDX and HMX by Anaerobic Granular Sludge with Enriched
      Sulfate and Nitrate.
AB  - RDX and HMX are widely used energetic materials and they are recognized as
      environmental contaminants at numerous locations. The present study investigated
      the biotransformation of RDX and HMX by anaerobic granular sludge under sulfate-
      and nitrate-enriched conditions. The results showed that RDX and HMX could be
      transformed by anaerobic granular sludge when nitrate was present. However, the
      biotransformation of RDX and HMX was negatively influenced, especially with high
      nitrate concentrations. Sulfate-enriched conditions were more favorable for the
      removal of ammunition compounds by anaerobic granular sludge than nitrate
      enriched conditions. The removal of RDX and HMX under both nitrate- and sulfate
      enriched conditions was facilitated by the use of glucose as additional
      substrate. This knowledge may help identify factors required for rapid removal of
      RDX and HMX in high-rate bioreactors. These results can also be applied to devise
      an appropriate and practical biological treatment strategy for explosive
      contaminated wastewater.

PMID- 28442009
TI  - [Enhanced Recovery after Surgery from Theory to Practice?What do We Need to Do?]
AB  - Enhanced recovery after surgery (ERAS) is a paradigm shift in perioperative care,
      resulting in substantial improvements in clinical outcomes, shorter length of
      hospital stay and cost savings. But the current ERAS either by application of
      breadth or depth is not enough, why? The main reason is the lack of "operability,
      evaluation, repetition" ERAS protocol and suitable for clinical extensive
      application protocol. How to form the clinical available protocol? Operational
      mainly refers to the clinical scheme is simple and feasible, and protocol
      compliance is good; Evaluate refers to the methods used before, during and after
      are the objective evaluation criteria and plan; Repeatable is clinical scheme
      repeatability in the process of single or multiple center.

PMID- 28442010
TI  - [Effect of Nm23-H1 Nuclear Localization on Proliferation of ?Human Lung
      Adenocarcinoma Cell Line A549].
AB  - BACKGROUND: Recent studies have indicated that Nm23-H1 is found in the nucleus,
      but previous studies have been based on the overexpression or suppression of Nm23
      H1 in the cytoplasm. Due to the lacking nuclear localization signal of Nm23-H1,
      these results cannot reflect or repeat cells in which Nm23-H1 mainly positioned
      in nuclei and whether they cause clinical biological effects. Therefore, to
      explore the effects of transposing Nm23-H1 from the cytoplasm to the nucleus
      during lung cancer cell proliferation, a vector with a nuclear localization
      signal of Nm23-H1 was constructed and A549 cells were transfected. METHODS: Gene
      recombination technology was used to construct pLentis-CMV-NME1-IRES2-PURO
      lentiviral vectors using a nuclear localization signal sequence, and the
      recombinant plasmid was verified using restriction enzyme analysis and
      sequencing. Nm23-H1 positioning and expression were performed after the stably
      transfected A549 cells were assessed by Western blot and confocal laser scanning
      microscope. The A549 cell proliferation was assessed using a cell counting kit-8.
      Flow cytometry was performed to assess the cell cycle distribution of A549 cells.
      RESULTS: The directional Nm23-H1 lentiviral vector was successfully constructed
      within the nucleus. Compared with that of the empty vector group, the
      proliferation rates of the transfection groups at 72 h, 96 h, and 120 h were
      remarkably increased (P<0.000,1). Moreover, the empty vector group of A549 cells
      in the G0/G1 phase proportion was 35.69%, which was higher than the 28.28% of the
      transfection group (t=1.461, P=0.217); furthermore, the transfection group of
      A549 cells in the G2/M phase proportion was 58.7% and that of the empty vector
      group was 31.30% (t=4.560, P=0.010). CONCLUSIONS: Human lung adenocarcinoma cell
      line A549 cells of Nm23-H1 nuclear localized mainly in the G2/M phase and the
      nuclear Nm23-H1 promoted A549 cell proliferation in vitro.

PMID- 28442011
TI  - [CK2alpha Regulates the Metastases and Migration of Lung Adenocarcinoma ?A549
      Cell Line through PI3K/Akt/GSK-3beta Signal Pathway].
AB  - BACKGROUND: Lung cancer is the leading cancer-related death worldwide. Patients
      with lung cancer mainly died of tumor metastasis and invasion. Protein kinase CK2
      is an ubiquitous serine/threonine protein kinase and is frequently upregulated in
      various human tumors. This study aims to explore the effect and molecular
      mechanism of the invasion and migration of lung adenocarcinoma A549 cells after
      knock-down of CK2alpha expression. METHODS: The pSilencerTM 4.1-siCK2alpha-eGFP
      of lentiviral-mediated shRNA was constructed. The expression of CK2alpha was
      knock-downed, and a stable A549 cell line was established. The invasion and
      migration of A549 cell line was detected through Transwell and Boyden chamber
      assays. The protein expression of the PI3K/Akt signaling pathway and mesenchymal
      to-epithelial transition (EMT) was evaluated using Western blot analysis.
      RESULTS: The invasion and migration of A549 cells were significantly inhibited
      after the knockdown of CK2alpha expression compared with that in the control
      group. p-PTEN, Akt, p-Akt473, p-Akt308, p-PDK1, p-c-Raf, and p-GSK-3beta were
      significantly downregulated, whereas PTEN was upregulated. Moreover, vimentin,
      beta-catenin, Snail, MMP2, and MMP9 were significantly downregulated after
      reducing the CK2alpha expression. CONCLUSIONS: CK2alpha might regulate the
      invasion and migration of A549 cells through the PI3K/Akt/GSK-3beta/Snail
      signaling pathway, which controls EMT in lung adenocarcinoma.?.

PMID- 28442012
TI  - [Preoperatiove Airway Bacterial Colonization: the Missing Link between Non-small
      Cell Lung Cancer Following Lobectomy and Postoperative Pneumonia?]
AB  - BACKGROUND: Surgical procedure is the main method of treating lung cancer.
      Meanwhile, postoperative pneumonia (POP) is the major cause of perioperative
      mortality in lung cancer surgery. The preoperative pathogenic airway bacterial
      colonization is an independent risk factor causing postoperative pulmonary
      complications (PPC). This cross-sectional study aimed to explore the relationship
      between preoperative pathogenic airway bacterial colonization and POP in lung
      cancer and to identify the high-risk factors of preoperative pathogenic airway
      bacterial colonization. METHODS: A total of 125 patients with non-small cell lung
      cancer (NSCLC) underwent thoracic surgery in six hospitals of Chengdu between May
      2015 and January 2016. Preoperative pathogenic airway bacterial colonization was
      detected in all patients via fiber bronchoscopy. Patients' PPC, high-risk
      factors, clinical characteristics, and the serum surfactant protein D (SP-D)
      level were also analyzed. RESULTS: The incidence of preoperative pathogenic
      airway bacterial colonization among NSCLC patients was 15.2% (19/125). Up to 22
      strains were identified in the colonization positive group, with Gram-negative
      bacteria being dominant (86.36%, 19/22). High-risk factors of pathogenic airway
      bacterial colonization were age (>=75 yr) and smoking index (>=400
      cigarettes/year). PPC incidence was significantly higher in the colonization
      positive group (42.11%, 8/19) than that in the colonization-negative group
      (16.04%, 17/106)(P=0.021). POP incidence was significantly higher in the
      colonization-positive group (26.32%, 5/19) than that in the colonization-negative
      group (6.60%, 7/106)(P=0.019). The serum SP-D level of patients in the
      colonization-positive group was remarkably higher than that in the colonization
      negative group [(31.25+/-6.09) vs (28.17+/-5.23)](P=0.023). The incidence of
      preoperative pathogenic airway bacterial colonization among NSCLC patients with
      POP was 41.67% (5/12). This value was 3.4 times higher than that among the
      patients without POP (OR=3.363, 95%CI: 1.467-7.711). CONCLUSIONS: An intimate
      correlation was observed between POP and pathogenic airway bacterial colonization
      in lung cancer. The high-risk factors of pathogenic airway bacterial colonization
      were age and smoking index.

PMID- 28442013
TI  - [Study on the Correlation Factors of 13, 14 Groups Lymph Node Metastasis of ?Non
      small Cell Lung Cancer].
AB  - BACKGROUND: Lymph node metastasis is one of the important factors affecting the
      tumor-node-matastasis (TNM) staging of lung cancer. In patients with surgery, 13
      groups and 14 groups of lymph nodes ignored because of the deep hidden in the
      lung. In this paper, the positive detection rate of 13 groups and the 14 groups
      of lymph nodes in non-small cell lung cancer (NSCLC) and their effects on
      pathological stage were studied. METHODS: 100 cases of NSCLC were collected from
      the Affiliated Hospital of Inner Mongolia Medical University as the research
      object, cut out the intrathoracic 2-12 group, 13, 14 lymph node metastasis rate
      for pathological examination, relationship factors of statistical analysis of the
      size of primary tumor, location, pathological type and lymph node. RESULTS: 100
      cases of patients with intrathoracic lymph node metastasis rate was 47.0%, with
      the 10-12 groups lymph node, N2 lymph nodes, 13, 14 groups lymph node positive
      rate had significant differences (P<0.05); T stage 13, 14 groups of lymph node
      detection rate has statistically significant difference (P<0.05); peripheral and
      central NSCLC stage N1 undetected rate no statistical difference (P>0.05);
      various pathological types of tumors between N1 missed rate had no significant
      difference (P>0.05). In addition, 12 patients were found to have non-tumor
      derived lobe lymph node metastasis. CONCLUSIONS: It is necessary to detect the
      metastatic lymph nodes of 13,14 group and non-tumor-derived lobe in NSCLC. It is
      helpful to obtain accurate TNM staging and to guide postoperative treatment.?.

PMID- 28442014
TI  - [Surgical Quality Surveillance and Sustaining Improvement of Lung Cancer Surgery
      Based on Standard Operation Procedure (SOP): Experience of Single Surgical Team].
AB  - BACKGROUND: Standard operation procedure (SOP) could standardize treatment
      procedure and reduce medical expenses, but SOP drawn by the government may not
      suit all medical institutions, so individual adjustment made by surgical team is
      necessary. METHODS: We recorded the information of patients undergoing lung
      resection, including postoperative hospital stay, medical expenses and ratio of
      video-assisted thoracoscopic surgery (VATS) rate to evaluate surgical quality
      sustaining improvement in terms of structure indicator, process indicator and
      outcome indicator, aiming at exploring the ideal postoperative hospital stay and
      the best indicators to evaluate surgical quality improvement. RESULTS: The
      average postoperative hospital stay reduced significantly between 2016 and 2013
      [(4.08+/-1.8) d vs (6.13+/-3.6) d, P<0.001)]. VATS rate increased from 2013-2016
      (17%->48%->68%->73%), as well as single port VATS rate (0%->2%->52%->66%).
      CONCLUSIONS: Surgical quality surveillance and sustaining improvement by surgical
      team could further reduce postoperative hospital stay and perioperative
      complications.

PMID- 28442015
TI  - [Expression and Clinical Significance of Progesterone and Adiponectin Receptor
      Family Member 3 in Lung Cancer].
AB  - BACKGROUND: Progesterone and adiponectin receptor family member 3 (PAQR3) is a
      recently discovered tumor suppressor gene, which affects the development of a
      tumor by inhibiting cell proliferation, cell malignant transformation,
      angiogenesis, and tumor metastasis. This study investigates the expression of
      PAQR3 in lung cancer and its clinical significance. METHODS: A total of 106
      patients with lung cancer received surgical treatment in hospital, and adjacent
      normal tissues of these patients were utilized as control group. The diagnosis of
      all patients was confirmed through clinical pathology. The expression of PAQR3
      protein was detected by immunohistochemistry in lung cancer and adjacent normal
      tissues. The clinical significance of its expression was also investigated.
      RESULTS: The positive expression rate of PAQR3 protein in lung cancer was lower
      than that in adjacent normal tissues (P<0.01). The positive expression rate of
      PAQR3 protein was unrelated to age, tumor size, and gender, but it exhibited a
      significant relationship with the pathological type and differentiation, TNM
      staging, and lymph node metastasis (P<0.05). Kaplan-Meier survival analysis
      showed that the five-year survival rate of patients with PAQR3 protein positive
      expression was higher than that in patients with negative expression (P=0.026).
      CONCLUSIONS: The expression of PAQR3 protein significantly decreased in lung
      cancer, indicating that PAQR3 protein plays an important role in the pathogenesis
      of PAQR3 in lung cancer.

PMID- 28442016
TI  - [Analysis of Postoperative Complications and Risk Factors of Patients with Lung
      Cancer through Clavien-Dindo Classification].
AB  - BACKGROUND: Postoperative complications (PCs) are contributing factors to patient
      mortality following lung resection. In this retrospective study, the Clavien
      Dindo classification was used to analyze the current incidence of PCs and
      identify the risk factors of different grades of PCs. METHODS: A total of 966
      lung cancer patients who underwent lobectomy in our department between June 2013
      and December 2014 were retrospectively enrolled. Patients were divided into two
      groups depending on the occurrence of PCs. The PCs were classified into four
      grades through the Clavien-Dindo classification, and the related risk factors of
      different grades were evaluated. RESULTS: Approximately 15.0% (145/966) of
      patients had PC (total incidence: 39.3%, 380/966). Among the 380 cases with PCs,
      the proportions of Clavien-Dindo grade I, grade II, grade III and grade IV or
      above complications were 6.8%, 75.3%, 15.0% and 2.9%, respectively. Binary
      Logistic regressions showed that preoperative forced expiratory volume in one
      second (FEV1), diffusion capacity for carbon monoxide of the lung (single
      breath)(DLco SB), and preoperative combined chronic obstructive pulmonary disease
      were the significant independent factors for PCs. FEV1 in preoperative pulmonary
      function was the significant risk factor for complications at Clavien-Dindo grade
      I, grade II, grade III, and above. CONCLUSIONS: Clavien-Dindo grade II
      complications are the most common complications within 30 days after lung cancer
      lobectomy. FEV1 is closely related to the occurrence of PCs and may potentially
      be one of the practical variables to assess the risk of occurrence of PCs.

PMID- 28442017
TI  - [Application of Bevacizumab in Non-small Cell Lung Cancer].
AB  - At present, non-small cell lung cancer is one of the highest incidence of cancers
      in the world, and its incidence increased year by year, this situation prompted
      people to continue to seek a variety of treatment in order to extend the survival
      of patients and improve the quality of life of patients. This review aims to
      discuss the progress of bevacizumab in the treatment of non-small cell lung
      cancer, through the clinical data so far to explore the clinical use of the drug,
      the choice of patients and the future direction of development.

PMID- 28442018
TI  - [Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted
      ?Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors].
AB  - At present the treatment of advanced non-small cell lung cancer enters a targeted
      era and develops rapidly. New drugs appear constantly. Small molecular tyrosine
      kinase inhibitors have occupied the biggest piece of the territory, which
      commonly have a clear biomarker as predictor, and show remarkable effect in
      specific molecular classification of patients. The epidermal growth factor
      tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic
      lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone
      advance. In recent years new generations of tyrosine kinase inhibitors have
      achieved a great success in patients with acquired resistance to the above two
      kinds of drugs. At the same time new therapeutic targets are constantly emerging.
      So in this paper, we reviewed and summarized the important drugs and clinical
      trails on this topic, and made a prospect of the future development.

PMID- 28442019
TI  - [Progress of c-MET Signaling Pathway and TKIs in Non-small Cell Lung Cancer].
AB  - c-MET is considered a promising oncogenic driver in non-small cell lung cancer
      (NSCLC) after the discovery of epidermal growth factor receptor (EGFR) and
      anaplastic lymphoma kinase (ALK). MET activation including gene mutation,
      amplification and protein overexpression, all of these are potential therapeutic
      targets and are associated with poor prognosis. Clinical evidence suggests a role
      for MET activation as both a primary oncogenic driver in subsets of lung cancer,
      and as a secondary driver of acquired resistance to EGFR-tyrosine kinase
      inhibitor (TKI). This review focuses on the MET activation in NSCLC and the
      latest trials of its treatment.

PMID- 28442021
TI  - 'Yarn with me': applying clinical yarning to improve clinician-patient
      communication in Aboriginal health care.
AB  - Although successful communication is at the heart of the clinical consultation,
      communication between Aboriginal patients and practitioners such as doctors,
      nurses and allied health professionals, continues to be problematic and is
      arguably the biggest barrier to the delivery of successful health care to
      Aboriginal people. This paper presents an overarching framework for practitioners
      to help them reorientate their communication with Aboriginal patients using
      'clinical yarning'. Clinical yarning is a patient-centred approach that marries
      Aboriginal cultural communication preferences with biomedical understandings of
      health and disease. Clinical yarning consists of three interrelated areas: the
      social yarn, in which the practitioner aims to find common ground and develop the
      interpersonal relationship; the diagnostic yarn, in which the practitioner
      facilitates the patient's health story while interpreting it through a biomedical
      or scientific lens; and the management yarn, that employs stories and metaphors
      as tools for patients to help them understand a health issue so a collaborative
      management approach can be adopted. There is cultural and research evidence that
      supports this approach. Clinical yarning has the potential to improve outcomes
      for patients and practitioners.

PMID- 28442022
TI  - General practice registrars' intentions for future practice: implications for
      rural medical workforce planning.
AB  - The models of practice that general practice registrars (GPRs) envisage
      undertaking will affect workforce supply. The aim of this research was to
      determine practice intentions of current GPRs in a regional general practice
      training program (Coast City Country General Practice Training). Questionnaires
      were circulated to 220 GPRs undertaking general practice placements to determine
      characteristics of ideal practice models and intentions for future practice.
      Responses were received for 99 participants (45%). Current GPRs intend to work an
      average of less than eight half-day sessions/week, with male participants
      intending to work more hours (t(91)=3.528, P=0.001). More than one-third of this
      regional cohort intends to practice in metropolitan centres. Proximity to family
      and friends was the most important factor influencing the choice of practice
      location. Men ranked remuneration for work as more important (t (88)=-4.280,
      P<0.001) and women ranked the ability to work part-time higher (t(94)=3.697,
      P<0.001). Fee-for-service payment alone, or in combination with capitation, was
      the preferred payment system. Only 22% of Australian medical graduates intend to
      own their own practice compared with 52% of international medical graduates
      (chi2(1)=8.498, P=0.004). Future general practitioners (GPs) intend to work fewer
      hours than current GPs. Assumptions about lifestyle factors, practice models and
      possible professional roles should be carefully evaluated when developing
      strategies to recruit GPs and GPRs into rural practice.

PMID- 28442023
TI  - Factors affecting the views and experiences of women living in the city centre of
      Manisa, Turkey, regarding domestic violence.
AB  - Domestic violence against women is an important social and public health problem
      worldwide resulting from unequal power relationships between men and women. The
      purpose of the present cross-sectional descriptive study was to determine the
      factors affecting the views and experiences of women living in the city centre of
      Manisa, Turkey, regarding domestic violence. The data were collected from a
      representative sample of women (n=873) in 2012. The socio-demographic
      questionnaire and the World Health Organization's Multi-country Study on Women's
      Health and Domestic Violence Against Women were used for data collection. The
      study results revealed that of the women, 14.8% were exposed to physical
      violence, 7.9% to sexual violence, 20.2% to emotional violence/abuse and 11.2% to
      economic violence/abuse within the last 12 months. Lower income level, lower
      social status, lower educational level, unemployment, being exposed to parental
      violence during childhood and being married to husbands exposed to parental
      violence during childhood were associated risk factors with domestic violence.
      The study results indicate that domestic violence against women is a common
      phenomenon in Manisa.

PMID- 28442024
TI  - Intracytoplasmic oxidative stress reverses epigenetic modifications in polycystic
      ovary syndrome.
AB  - In polycystic ovary syndrome (PCOS), substantial genetic and environmental
      alterations, along with hyperandrogenism, affect the quality of oocytes and
      decrease ovulation rates. To determine the mechanisms underlying these
      alterations caused specifically by an increase in plasma androgens, the present
      study was performed in experimentally-induced PCOS mice. As the study model,
      female B6D2F1 mice were treated with dehydroepiandrosterone (DHEA, 6mg per 100g
      bodyweight). After 20 days, oocytes at the germinal vesicle and metaphase II
      stages were retrieved from isolated ovaries and subsequent analyses of oocyte
      quality were performed for each mouse. DHEA treatment resulted in excessive
      abnormal morphology and decreased polar body extrusion rates in oocytes, and was
      associated with an increase in oxidative stress. Analysis of fluorescence
      intensity revealed a significant reduction of DNA methylation and dimethylation
      of histone H3 at lysine 9 (H3K9) in DHEA-treated oocytes, which was associated
      with increased acetylation of H4K12. Similarly, mRNA expression of DNA
      methyltransferase-1 and histone deacetylase-1 was significantly decreased in DHEA
      treated mice. There was a significant correlation between excessive reactive
      oxygen species (ROS) production and increased histone acetylation, which is a
      novel finding and may provide new insights into the mechanism causing PCOS. The
      results of the present study indicate that epigenetic modifications of oocytes
      possibly affect the quality of maturation and ovulation rates in PCOS, and that
      the likely mechanism may be augmentation of intracytoplasmic ROS.

PMID- 28442025
TI  - Protective effects of polydatin on experimental testicular torsion and detorsion
      injury in rats.
AB  - Oxidative stress plays a critical role in the process of testicular torsion and
      detorsion (T/D). The purpose of the present study was to investigate the
      protective effect of polydatin (PD) on testicular T/D injury. Rats were randomly
      divided into three groups, a sham group, a group subjected to 2h torsion followed
      by 24h detorsion and a group subjected to T/D and injected i.p. with 20mgkg-1 PD
      30min before detorsion. Unilateral orchiectomy was performed after 24h of
      reperfusion. Half the testes were prepared for histological examination by
      haematoxylin-eosin staining and the terminal deoxyribonucleotidyl transferase
      mediated dUTP-digoxigenin nick end-labelling (TUNEL) technique. In the remaining
      tissues, levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase
      (GPx) and superoxide dismutase (SOD) were determined, as was the expression of
      several apoptosis-related proteins. Compared with the T/D group, PD pretreatment
      significantly ameliorated the morphological damage, lowered the Cosentino
      histological score and increased the mean number of germ cell layers and
      Johnsen's testicular biopsy score. In addition, PD treatment markedly decreased
      MDA levels and upregulated CAT, GPx and SOD activity. Furthermore, PD decreased
      T/D-induced germ cell-specific apoptosis, attenuated the activation of caspase-3,
      caspase-8, caspase-9 and poly(ADP-ribose) polymerase and increased the Bcl-2/Bax
      ratio. The findings indicate that PD has a protective effect against testicular
      T/D injuries, especially at the histological, antioxidative stress and
      antiapoptotic levels.

PMID- 28442028
TI  - Revisiting the ability of Australian primary healthcare services to respond to
      health inequity.
AB  - Equity of access and reducing health inequities are key objectives of
      comprehensive primary health care. However, the supports required to target
      equity are fragile and vulnerable to changes in the fiscal and political
      environment. Six Australian primary healthcare services, five in South Australia
      and one in the Northern Territory, were followed over 5 years (2009-2013) of
      considerable change. Fifty-five interviews were conducted with service managers,
      staff, regional health executives and health department representatives in 2013
      to examine how the changes had affected their practice regarding equity of access
      and responding to health inequity. At the four state government services, seven
      of 10 previously identified strategies for equity of access and services' scope
      to facilitate access to other health services and to act on the social
      determinants of health inequity were now compromised or reduced in some way as a
      result of the changing policy environment. There was a mix of positive and
      negative changes at the non-government organisation. The community-controlled
      service increased their breadth of strategies used to address health equity.
      These different trajectories suggest the value of community governance, and
      highlight the need to monitor equity performance and advocate for the importance
      of health equity.

PMID- 28442026
TI  - Neuromodulatory effect of oestradiol in the metabolism of ovarian progesterone
      and oestradiol during dioestrus II: participation of the superior mesenteric
      ganglion.
AB  - The aims of the present study were to determine: (1) whether oestradiol (E2) in
      the superior mesenteric ganglion (SMG) modifies the release of ovarian
      progesterone (P4), androstenedione (A2) and E2, the activity and gene expression
      of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 20alpha-HSD and the
      expression of P450 aromatase (Cyp19a1) and (2) whether any such modifications are
      related to changes in ovarian nitric oxide (NO) and noradrenaline (NA) levels
      during dioestrus II. Using an ex vivo SMG-ovarian nervous plexus-ovary system,
      ovarian P4 release was measured following the addition E2 plus tamoxifen (Txf)
      (10-6M) to the ganglion, whereas A2, E2, NA and NO were measured following the
      addition of E2 alone. Steroids were measured by radioimmunoassay, NA
      concentrations were determined by HPLC and gene expression was evaluated using
      reverse transcription-polymerase chain reaction. Oestradiol in the ganglion
      decreased ovarian P4, E2 and NA release, as well as 3beta-HSD activity, but
      increased the release of A2 and nitrites, as well as the 20alpha-HSD expression
      and its activity. No changes were observed in Cyp19a1 gene expression. The
      addition of E2 plus Txf to the ganglion reversed the effects of E2 alone. The
      action of oestradiol in SMG favours the beginning of functional luteolysis, due
      to an increase in NO release and a decrease in NA in the ovary. These results may
      help elucidate the role of E2 in hormone-dependent pathologies in women.

PMID- 28442029
TI  - Cross-cultural training of general practitioner registrars: how does it happen?
AB  - An equitable multicultural society requires general practitioners (GPs) to be
      proficient in providing health care to patients from diverse backgrounds. GPs are
      required to have a certain attitudes, knowledge and skills known as cultural
      competence. Given its importance to registrar training, the aim of this study was
      to explore ways in which GP registrars are currently developing cultural
      competence. This study employed a survey design for GP registrars in Western
      Sydney. Training approaches to cultural competence that are relevant to the
      Australian General Practice setting include exposure to diversity, attitudes,
      knowledge and skills development. The 43 GP registrar respondents in Western
      Sydney are exposed to a culturally diverse patient load during training.
      Registrars report a variety of teachings related to cross-cultural training, but
      there is little consistency, with the most common approach entailing listening to
      patients' personal stories. Exposure to cultural diversity appears to be an
      important way in which cultural competency is developed. However, guidance and
      facilitation of skills development throughout this exposure is required and
      currently may occur opportunistically rather than consistently.

PMID- 28442031
TI  - Improving processes that underpin Australian primary health care.

PMID- 28442032
TI  - John Furler - thanks and best wishes.

PMID- 28442033
TI  - Out-of-pocket healthcare expenditure and chronic disease - do Australians forgo
      care because of the cost?
AB  - Although we do know that out-of-pocket healthcare expenditure is relatively high
      in Australia, little is known about what health conditions are associated with
      the highest out-of-pocket expenditure, and whether the cost of healthcare acts as
      a barrier to care for people with different chronic conditions. Cross-sectional
      analysis using linear and logistic regression models applied to the Commonwealth
      Fund international health policy survey of adults aged 18 years and over was
      conducted in 2013. Adults with asthma, emphysema and chronic obstructive
      pulmonary disease (COPD) had 109% higher household out-of-pocket healthcare
      expenditure than did those with no health condition (95% CI: 50-193%); and adults
      with depression, anxiety and other mental health conditions had 95% higher
      household out-of-pocket expenditure (95% CI: 33-187%). People with a chronic
      condition were also more likely to forego care because of cost. People with
      depression, anxiety and other mental health conditions had 7.65 times higher odds
      of skipping healthcare (95% CI: 4.13-14.20), and people with asthma, emphysema
      and chronic obstructive pulmonary disease had 6.16 times higher odds of skipping
      healthcare (95% CI: 3.30-11.50) than did people with no health condition. People
      with chronic health conditions in Canada, the United Kingdom, Germany, France,
      Norway, Sweden and Switzerland were all significantly less likely to skip
      healthcare because of cost than were people with a condition in Australia. The
      out-of-pocket cost of healthcare in Australia acts as a barrier to accessing
      treatment for people with chronic health conditions, with people with mental
      health conditions being likely to skip care. Attention should be given to the
      accessibility and affordability of mental health services in Australia.

PMID- 28442034
TI  - Improving follow-up care for women with a history of gestational diabetes:
      perspectives of GPs and patients.
AB  - This paper investigates factors influencing women's engagement with diabetes
      preventative care after a pregnancy with gestational diabetes (GDM) from the
      perspectives of GPs and women and explores the role of the GP in that care.
      Qualitative research using semi-structured interviews with women who had
      experienced GDM (n=16) and GPs (n=18) were conducted and a thematic content
      analysis conducted. Women's interviews explored their experience of GDM, factors
      influencing, and engagement with, follow-up care for diabetes prevention and role
      of the GP in that care. GP interviews explored postnatal care provided to women
      with GDM, the role of the GP in that care and perceived factors influencing a
      mother's engagement in her self-care. Three themes were identified: (1) advice
      and testing; (2) role of the GP; and (3) barriers and enablers to care.
      Significant consensus about the role of the GP and barriers and enablers to care
      existed. Both groups believed post GDM follow-up is best done by GPs and
      suggested recall and reminders would improve care. GPs gave consistent exercise
      advice, but lacked consensus on follow-up testing, dietary and weight-loss
      advice. Women's health literacy influenced how they viewed their GPs role.
      Consensus guidelines on follow-up testing and diabetes prevention advice,
      tailored advice according to health literacy and addressing barriers to care
      would likely improve the capacity of GPs to prevent unnecessary conversion to
      type 2 diabetes in these at-risk women.

PMID- 28442035
TI  - Manufactured home villages in Australia - a melting pot of chronic disease?
AB  - Manufactured home villages (MHVs) are an increasingly popular housing option for
      older Australians. This paper reports a cross-sectional survey that sought to
      describe the health status and health service access of MHV residents. The survey
      tool comprised demographic and health status items, primary healthcare access
      perceptions and the World Health Organization Quality of Life tool (WHOQOL-BREF).
      One-hundred-eighty-six MHV residents from regional NSW completed the survey.
      Hypertension (54.8%) and arthritis (46.5%) were the most prevalent chronic
      diseases reported. Overall, respondents expressed a high level of satisfaction
      with the sense of safety and security (82.8%), neighbours (69.4%) and the overall
      location of the villages (66.7%). There was good to excellent internal
      consistency of all four WHOQOL-BREF domain scores, with a comparatively lower
      sample mean score for the 'Physical' and 'Psychological' domains. MHV residents
      are a significant cohort of older people with high rates of chronic disease and
      reasonably poor access to transport services, which affects their capacity to
      access health services. They also have comparatively low levels of quality of
      physical and psychological life along with low levels of satisfaction with their
      health.

PMID- 28442037
TI  - Needs-gap analysis on culturally and linguistically diverse grandparent carers'
      'hidden issues': a quality improvement project.
AB  - In Australia, a significant number of culturally and linguistically diverse
      (CALD) grandparents are sole carers for their grandchildren. Available
      information on the impact of caring on CALD grandparents and the ability of
      service providers to respond to their needs is limited. Our needs-gap analysis
      quality improvement project aimed to uncover 'hidden issues' for CALD grandparent
      carers so that services can be improved. One hundred service providers, such as
      community and aged-care services, child and/or grandparent support services and
      CALD-specific services, were approached using six structured questions. Six
      consultative forums on the caring role, issues encountered, and what needed to be
      done, were conducted with African, Asian, Spanish, Middle Eastern, European,
      Pacific Island and Maori grandparent carers in Queensland. The data were
      qualitatively analysed. Six themes emerged: 1) service provider and grandparent
      carer perception that there was limited research on CALD grandparents; 2)
      inadequate legal and financial support; 3) barriers to accessing information; 4)
      lack of childcare options; 5) transport difficulties; and 6) inadequate
      technological skills. Our findings provide insight to health service providers on
      the 'hidden issues' so that they can better assist CALD grandparent carers by
      improving access to relevant information, referrals and resources.

PMID- 28442038
TI  - Is there a role for a primary health nurse in a learning support team in a
      disadvantaged high school? Evaluation of a pilot study.
AB  - Disadvantaged children experience more health problems and have poorer
      educational outcomes compared with students from advantaged backgrounds. This
      paper presents the quantitative and qualitative findings from a pilot study to
      determine the impact of the Healthy Learner model, where an experienced primary
      care nurse was embedded in a learning support team in a disadvantaged high
      school. Students entering high school with National Assessment Program, Literacy
      and Numeracy (NAPLAN) scores in the lowest quartile for the school were assessed
      by the nurse and identified health issues addressed. Thirty-nine students were
      assessed in 2012-13 and there were up to seven health problems identified per
      student, ranging from serious neglect to problems such as uncorrected vision or
      hearing. Many of these problems were having an impact on the student and their
      ability to engage in learning. Families struggled to navigate the health system,
      they had difficulty explaining the student's problems to health professionals and
      costs were a barrier. Adding a nurse to the learning support team in this
      disadvantaged high school was feasible and identified considerable unmet health
      needs that affect a student's ability to learn. The families needed extensive
      support to access any subsequent health care they required.

PMID- 28442039
TI  - Connecting Care in the Community: what works and what doesn't.
AB  - As the burden of chronic and complex disease grows, there is an emphasis on
      programs that enhance the quality of care within primary care. The Connecting
      Care in the Community (CCC) program is an example of the implementation of care
      integration. This qualitative study sought to explore the experiences general
      practice staff face in managing clients with chronic and complex care issues, and
      their perceptions of the contribution of the CCC program to this care. Seventeen
      general practice staff from 11 practices throughout the Illawarra/Shoalhaven
      region participated in semistructured interviews. Five main themes emerged: (1)
      awareness of the CCC program; (2) varying program exposure and value placed on
      the program; (3) practice 'busyness' and role confusion; (4) communication and
      information sharing; and (5) the need for staff education and knowledge of local
      resources. If policymakers and healthcare organisations can gain a better
      understanding of the experiences of general practice staff, they will be able to
      design and implement programs that best meet the needs of the providers that they
      are attempting to integrate.

PMID- 28442040
TI  - Corrigendum to: Medication-taking behaviour in New South Wales patients with type
      2 diabetes: an observational study.
AB  - This study aimed to (1) determine adherence to diabetes medication in type 2
      diabetes (T2D) patients; (2) describe respondents' attitudes and beliefs about
      medications, and barriers to adherence; and (3) to model predictors of non
      adherence. Data were collected using online and postal surveys. Diabetes patients
      aged ?18 years who were members of the Australian Diabetes Council were invited
      to participate. Main outcome measures were adherence to diabetes medication using
      8-item Morisky Medication Adherence Score (MMAS-8) and beliefs about medication
      using the Beliefs about Medicines Questionnaire. A total of 543 T2D patients
      responded to the survey. The median (interquartile range) MMAS-8 score was 6.8
      (5.0-7.0). The prevalence of adherence (MMAS-8 score ?6) was 64.6%. The
      proportion of respondents who expressed concern about taking medications was
      53.6%. Potential predictors of adherence included age (OR, 1.83; 95% CI, 1.19
      2.82), concern about medication (OR, 0.91; 95% CI, 0.87-0.96), knowledge of
      diabetes (OR, 0.85, 95% CI, 0.73-0.99), having difficulty in paying for
      medication (OR, 0.51; 95% CI ,0.33-0.79), having more than one regular pharmacy
      (OR, 0.59; 95% CI, 0.36-0.95), and using insulin (OR, 0.49; 95% CI, 0.30-0.81).
      Adherence to taking diabetes medication in a sample of the Australian T2D patient
      population was suboptimal. An understanding of medication-taking behaviour will
      assist health-care professionals to deliver appropriate and effective
      interventions to enhance adherence and optimise diabetes control in T2D patients.

PMID- 28442041
TI  - Cytokine gene expression at the maternal-fetal interface after somatic cell
      nuclear transfer pregnancies in small ruminants.
AB  - The present retrospective study investigated pregnancy rates, the incidence of
      pregnancy loss and large offspring syndrome (LOS) and immune-related gene
      expression of sheep and goat somatic cell nuclear transfer (SCNT) pregnancies. We
      hypothesised that significantly higher pregnancy losses observed in sheep
      compared with goat SCNT pregnancies are due to the increased amounts of T-helper
      1 cytokines and proinflammatory mediators at the maternal-fetal interface. Sheep
      and goat SCNT pregnancies were generated using the same procedure. Control
      pregnancies were established by natural breeding. Although SCNT pregnancy rates
      at 45 days were similar in both species, pregnancy losses between 45 and 60 days
      of gestation and the incidence of LOS were significantly greater in sheep than in
      goats. At term, the expression of proinflammatory genes in sheep SCNT placentas
      was increased, whereas that in goats was similar to that in control animals.
      Genes with altered expression in sheep SCNT placentas included cytotoxic T
      lymphocyte-associated protein 4 (CTLA4), interleukin 2 receptor alpha (IL2RA),
      cluster of differentiation 28 (CD28), interferon gamma (IFNG), interleukin 6
      (IL6), interleukin 10 (IL10), transforming growth factor beta 1 (TGFB1), tumor
      necrosis factor alpha (TNF-alpha), interleukin 1 alpha (IL1A) and chemokine (C-X
      C motif) ligand 8 (CXCL8). Major histocompatibility complex-I protein expression
      was greater in sheep and goat SCNT placentas at term than in control pregnancies.
      An unfavourable immune environment is present at the maternal-fetal interface in
      sheep SCNT pregnancies.

PMID- 28442042
TI  - Growth arrest specific 1 (Gas1) and glial cell line-derived neurotrophic factor
      receptor alpha1 (Gfralpha1), two mouse oocyte glycosylphosphatidylinositol
      anchored proteins, are involved in fertilisation.
AB  - Recently, Juno, the oocyte receptor for Izumo1, a male immunoglobulin, was
      discovered. Juno is an essential glycosylphosphatidylinositol (GIP)-anchored
      protein. This result did not exclude the participation of other GIP-anchored
      proteins in this process. After bibliographic and database searches we selected
      five GIP-anchored proteins (Cpm, Ephrin-A4, Gas1, Gfra1 and Rgmb) as potential
      oocyte candidates participating in fertilisation. Western blot and
      immunofluorescence analyses showed that only three were present on the mouse
      ovulated oocyte membrane and, of these, only two were clearly involved in the
      fertilisation process, namely growth arrest specific 1 (Gas1) and glial cell line
      derived neurotrophic factor receptor alpha1 (Gfralpha1). This was demonstrated by
      evaluating oocyte fertilisability after treatment of oocytes with antibodies
      against the selected proteins, with their respective short interference RNA or
      both. Gfralpha1 and Gas1 seem to be neither redundant nor synergistic. In
      conclusion, oocyte Gas1 and Gfralpha1 are both clearly involved in fertilisation.

PMID- 28442043
TI  - Preantral follicle density in ovarian biopsy fragments and effects of mare age.
AB  - The aims of the present study were to: (1) evaluate preantral follicle density in
      ovarian biopsy fragments within and among mares; (2) assess the effects of mare
      age on the density and quality of preantral follicles; and (3) determine the
      minimum number of ovarian fragments and histological sections needed to estimate
      equine follicle density using a mathematical model. The ovarian biopsy pick-up
      method was used in three groups of mares separated according to age (5-6, 7-10
      and 11-16 years). Overall, 336 preantral follicles were recorded with a mean
      follicle density of 3.7 follicles per cm2. Follicle density differed (P<0.05)
      among animals, ovarian fragments from the same animal, histological sections and
      age groups. More (P<0.05) normal follicles were observed in the 5-6 years (97%)
      than the 11-16 years (84%) age group. Monte Carlo simulations showed a higher
      probability (90%; P<0.05) of detecting follicle density using two experimental
      designs with 65 histological sections and three to four ovarian fragments. In
      summary, equine follicle density differed among animals and within ovarian
      fragments from the same animal, and follicle density and morphology were
      negatively affected by aging. Moreover, three to four ovarian fragments with 65
      histological sections were required to accurately estimate follicle density in
      equine ovarian biopsy fragments.

PMID- 28442044
TI  - Serial transvaginal ultrasound-guided biopsy of the porcine corpus luteum in
      vivo.
AB  - The aims of the present study was to develop and describe a transvaginal
      ultrasound-guided biopsy method for luteal tissue in the porcine and to evaluate
      the effects of the method on the reproductive tract, ovarian status and pregnancy
      status. Biopsies were performed in four multiparous sows on Days 9 and 15 of
      three consecutive oestrous cycles; the size and histological composition of the
      samples obtained were evaluated and the reproductive tract of the sows was
      monitored. Furthermore, biopsies were performed in 26 multiparous sows on Days 10
      and 13 after insemination, and the pregnancy rate, gestation length and
      subsequent litter size were evaluated. RNA was extracted from the samples
      obtained and the quality and quantity were determined. Altogether, 76 biopsies
      were performed and 38 samples were obtained. Compared with sows from which no
      samples were obtained (n=6), sows from which one or more samples were obtained
      (n=24) were older (parity 5.0+/-2.8 vs 2.2+/-0.4, mean+/-s.d.), heavier (290+/-26
      vs 244+/-27kg) and had higher back fat (11.4+/-2.7 vs 6.4+/-2.5mm; P<0.05 for
      all). No effect of the biopsies (P>0.05) was observed on the cyclicity and
      reproductive organs of the sows, or on corpus luteum diameter on Day 13 (8.9+/
      1.0 vs 9.2+/-1.1mm), pregnancy rate (95% vs 96%), gestation length (115+/-1 vs
      115+/-1 days) and subsequent litter size (12.7+/-2.5 vs 13.3+/-2.8) between sows
      from which samples were obtained and those from which no samples were obtained.
      The samples obtained had a diameter of 1mm and contained heterogeneous tissue
      with various cell types. The RNA quantity was 520+/-160ug per sample and the RNA
      integrity number was 8.5+/-1.0. In conclusion, an ultrasound-guided biopsy method
      for ovarian tissue, which can be used for gene expression studies, was
      established in the porcine. No effect on corpus luteum function was found.

PMID- 28442045
TI  - Lower dietary n-6 : n-3 ratio and high-dose vitamin E supplementation improve
      sperm morphology and oxidative stress in boars.
AB  - A 2*2 factorial experiment (10 boars per treatment) was conducted for 16 weeks to
      evaluate the effects of the dietary n-6:n-3 ratio (14:1 vs 6:1) and vitamin E
      (200 vs 400mg kg-1) on boar sperm morphology and oxidative stress. Sperm
      mitochondrial membrane potential (MMP), reactive oxygen species (ROS), DNA damage
      (8-hydroxydeoxyguanosine; 8-OHdG), seminal lipoperoxidation (malondialdehyde;
      MDA) and antioxidant capacity in the serum, spermatozoa and seminal plasma were
      assessed as indicators of oxidative stress. Sperm production was similar among
      groups but increased (P<0.05) throughout the 16 weeks of the study. Although
      sperm alpha-tocopherol content, ROS and seminal MDA did not differ between the
      two dietary n-6:n-3 ratio treatments, enhanced antioxidant enzyme activity and
      MMP, but decreased 8-OHdG, were found in spermatozoa from boars consuming the 6:1
      diet. The diet with the 6:1 ratio positively affected sperm morphology at Weeks
      12 and 16 (P<0.05). The alpha-tocopherol content and antioxidant capacity
      increased in boars with increasing levels of vitamin E supplementation. Compared
      with low-dose vitamin E, high-dose vitamin E supplementation improved sperm
      morphology. Overall, the results indicate that an n-6:n-3 ratio of 6:1 and 400
      mg/kg vitamin E have beneficial effects on sperm morphology by improving
      antioxidative stress.

PMID- 28442046
TI  - Morphometric developmental pattern of bovine handmade cloned concepti in late
      pregnancy.
AB  - Cloning procedures often interfere with conceptus growth and life ex utero, in a
      set of symptoms known as abnormal offspring syndrome (AOS). The aim of the
      present study was to compare the developmental pattern of in vivo-derived (IVD),
      IVF-derived and handmade cloning-derived (NT-HMC) Day 225 bovine concepti using
      established procedures. Pregnancy diagnosis was performed on Day 30 following
      blastocyst transfer on Day 7. Conceptus morphometry was assessed by
      ultrasonography on Day 51, and on Day 225 pregnant cows were killed for
      morphological examination of concepti. Pregnancy outcome was similar between
      groups, with greater pregnancy losses in the first trimester (70.6%) and smaller
      fetuses on Day 51 in the NT-HMC group than in the IVD (14.3%) and IVF (20.0%)
      groups. However, NT-HMC-derived concepti were twofold larger on Day 225 of
      gestation than controls. A higher frequency (63.5%) of placentomes larger than
      the largest in the IVD group was observed in the NT-HMC group, which may be
      relevant to placental function. Conceptus traits in the IVF group were similar to
      the IVD controls, with only slight changes in placentome types. Morphological
      changes in cloned concepti likely affected placental function and metabolism,
      disrupting the placental constraining mechanism on fetal growth in mid- to late
      pregnancy.

PMID- 28442047
TI  - Increased frequency of chromosome congression defects and aneuploidy in mouse
      oocytes cultured at lower temperature.
AB  - Optimal culture conditions are essential for successful IVM of mammalian oocytes
      and for their further development into an embryo. In the present study we used
      live cell imaging microscopy to assess the effects of suboptimal culture
      temperature on various aspects of IVM, including duration of meiosis I, dynamics
      of polar body extrusion, chromosome congression, anaphase-promoting
      complex/cyclosome (APC/C) activation and aneuploidy. The data showed that even a
      small deviation from the optimal incubation temperature causes marked changes in
      the duration and synchronicity of meiosis, APC/C activity and the frequency of
      chromosome congression and segregation errors. In vitro manipulation and
      maturation of germ cells is widely used in both human and animal artificial
      reproduction techniques. Mammalian oocytes are naturally prone to chromosomal
      segregation errors, which are responsible for severe mental and developmental
      disorders. The data presented herein demonstrate that exposure of mouse oocytes
      to suboptimal temperature during manipulation and maturation could further
      increase the frequency of chromosome segregation defects in these cells.

PMID- 28442048
TI  - Expression of 17beta-hydroxysteroid dehydrogenase and the effects of LH, FSH and
      prolactin on oestrone and 17beta-oestradiol secretion in the endometrium of pigs
      during early pregnancy and the oestrous cycle.
AB  - The endometrium of pregnant and cyclic pigs is a source of oestrone (E1) and
      17beta-oestradiol (E2). However, the roles of LH, FSH and prolactin (PRL) as
      regulators of endometrial steroidogenesis, and the presence of 17beta
      hydroxysteroid dehydrogenase (17beta-HSD) in the porcine endometrium, remain
      unknown. Therefore, in the present study we examined 17beta-HSD expression and
      the effects of LH, FSH and PRL on E1 and E2 release in vitro in endometrial
      explants harvested from gravid pigs on Days 10-11 (embryo migration within the
      uterus), 12-13 (maternal recognition of pregnancy) and 15-16 (beginning of
      implantation) and compared them with results obtained in non-gravid pigs. The
      results show that: (1) endometrial 17beta-HSD activity was decreased on Days 15
      16 in pregnant and cyclic pigs compared with the preceding days; (2) LH, FSH and
      PRL increased endometrial E1 secretion on Days 10-11 and 15-16 of pregnancy and
      on Days 12-13 and 15-16 of the oestrous cycle; and (3) LH, FSH and PRL increased
      endometrial E2 secretion on Days 15-16 of pregnancy and during the days studied
      in the oestrous cycle. In conclusion, data suggest that LH, FSH and PRL affect
      endometrial secretion of estrogens in pigs.

PMID- 28442049
TI  - Prion protein 2 (dublet) gene (PRND): role in ovine semen capacitation,
      cryopreservation and fertility.
AB  - The aim of the present study was to examine the role of Doppel protein in the
      capacitation process and fertilising ability of both fresh and frozen-thawed (FT)
      spermatozoa from rams carrying different prion protein 2 (dublet) (PRND) gene
      polymorphisms. The detection efficacy of new anti-Doppel monoclonal antibodies
      and PRND mRNA quantification were also explored in ovine spermatozoa. Three
      different genotypes (AA, GA, GG) were identified for codon 26 of ovine PRND
      c.78G>A. Using flow cytometry, a higher fluorescence was detected in fresh
      compared with FT sperm samples incubated with anti-Doppel primary and fluorescein
      isothiocyanate-conjugated secondary antibodies (P<0.05). Capacitation was
      affected by semen treatment (fresh and FT) and male PRND genotype (P<0.05). After
      IVF, the use of fresh semen resulted in a higher cleavage rate than the use of FT
      spermatozoa (P=0.004). IVF using spermatozoa from individuals classified as
      carriers of the AA or GA PRND genotypes resulted in higher cleavage rates than
      seen using spermatozoa from GG carriers (P<=0.0006). Finally, using semen from
      rams with the AA PRND genotype resulted in the highest Day 6 and Day 8 embryo
      rates (P<=0.04). In conclusion, the results of the present study confirm that the
      identification of different PRND genotypes is important for studying the sperm
      capacitation process and for improving sperm cryoresistance and embryo
      production. Furthermore, the detection of Doppel in ejaculated ovine spermatozoa,
      along with its low expression after cryopreservation, strongly suggests an
      important physiological function of this protein in male fertility.

PMID- 28442050
TI  - Lonidamine-ethyl ester-mediated remodelling of the Sertoli cell cytoskeleton
      induces phosphorylation of plakoglobin and promotes its interaction with alpha
      catenin at the blood-testis barrier.
AB  - Several compounds affect male fertility by disrupting the adhesion of germ cells
      to Sertoli cells, which results in the release of undeveloped germ cells into the
      seminiferous tubule lumen that are incapable of fertilising the ovum. Indazole
      carboxylic acids are one class of compounds exhibiting such effects and they have
      been investigated as non-hormonal contraceptives for potential human use. The
      aims of this study were to investigate the effects of lonidamine-ethyl ester, an
      indazole carboxylic acid, on spermatogenesis and cell junctions, in particular,
      desmosomes. We found two doses of lonidamine-ethyl ester at 50mg kg-1 to disrupt
      Sertoli-germ cell adhesion. By light and fluorescent microscopy, pronounced
      changes were observed in the distribution of actin microfilaments and
      intermediate filaments, as well as in the localisation of plakoglobin, a protein
      with structural and signalling roles at the desmosome and adherens junction at
      the blood-testis barrier. Furthermore, immunoblotting and immunoprecipitation
      experiments using testis lysates revealed a significant upregulation (P<0.01) of
      plakoglobin and Tyr-phosphorylated plakoglobin. Co-immunoprecipitation
      experiments showed an increase in the interaction between plakoglobin and fyn
      proto-oncogene, an Src family non-receptor tyrosine kinase, after treatment, as
      well as an increase in the interaction between plakoglobin and alpha-catenin.
      Taken collectively, these data indicate that a disruption of Sertoli cell and
      spermatocyte-spermatid adhesion in the seminiferous epithelium by lonidamine
      ethyl ester results in the phosphorylation of plakoglobin, thereby promoting its
      interaction with alpha-catenin at the blood-testis barrier.

PMID- 28442051
TI  - Cerium oxide nanoparticles (CeO2 NPs) improve the developmental competence of in
      vitro-matured prepubertal ovine oocytes.
AB  - The present study investigated whether supplementation with different doses of
      cerium dioxide nanoparticles (CeO2 NPs) during in vitro maturation (IVM) of
      prepubertal ovine oocytes influenced their embryonic development in vitro.
      Cumulus-oocyte complexes derived from the ovaries of slaughtered prepubertal
      sheep underwent IVM with CeO2NPs (0, 44, 88 or 220ug mL-1). Matured oocytes were
      fertilised in vitro and zygotes were cultured for 7 days. The results
      demonstrated that CeO2NPs were internalised in the cumulus cells and not in the
      oocyte. The treatment with CeO2NPs did not affect nuclear maturation or
      intracellular levels of reactive oxygen species of the oocytes. The percentage of
      oocytes with regular chromatin configuration and cytoskeleton structures when
      treated with 44ug mL-1 CeO2NPs was similar to oocytes matured in the absence of
      CeO2NPs and significantly higher than those treated with 88 or 220ug mL-1
      CeO2NPs. The relative quantification of transcripts in the cumulus cells of
      oocytes matured with 44ug mL-1 CeO2NPs showed a statistically lower mRNA
      abundance of BCL2-associated X protein (BAX), B-cell CLL/lymphoma 2 (BCL2) and
      superoxide dismutase 1 (SOD1) compared with the 0ug mL-1 CeO2 NPs group. A
      concentration of 44ug mL-1 CeO2NPs significantly increased the blastocyst yield
      and their total, inner cell mass and trophectoderm cell numbers, compared with
      the 0 and 220ug mL-1 groups. A low concentration of CeO2NPs in the maturation
      medium enhanced in vitro embryo production of prepubertal ovine oocytes.

PMID- 28442053
TI  - Persistent pain management in Australian general practice.

PMID- 28442054
TI  - When colocation is not enough: a case study of General Practitioner Super Clinics
      in Australia.
AB  - Developed nations are implementing initiatives to transform the delivery of
      primary care. New models have been built around multidisciplinary teams,
      information technology and systematic approaches for chronic disease management
      (CDM). In Australia, the General Practice Super Clinic (GPSC) model was
      introduced in 2010. A case study approach was used to illustrate the development
      of inter-disciplinary CDM over 12 months in two new, outer urban GPSCs. A social
      scientist visited each practice for two 3-4-day periods. Data, including practice
      documents, observations and in-depth interviews (n=31) with patients, clinicians
      and staff, were analysed using the concept of organisational routines. Findings
      revealed slow, incremental evolution of inter-disciplinary care in both sites.
      Clinic managers found the facilitation of inter-disciplinary routines for CDM
      difficult in light of competing priorities within program objectives and the
      demands of clinic construction. Constraints inherent within the GPSC program, a
      lack of meaningful support for transformation of the model of care and the lack
      of effective incentives for collaborative care in fee-for-service billing
      arrangements, meant that program objectives for integrated multidisciplinary care
      were largely unattainable. Findings suggest that the GPSC initiative should be
      considered a program for infrastructure support rather than one of primary care
      transformation.

PMID- 28442055
TI  - Home care packages: insights into the experiences of older people leading up to
      the introduction of consumer directed care in Australia.
AB  - This paper reports phase one, conducted from March to June 2015, of a two-phase,
      qualitative descriptive study designed to explore the perceptions and experiences
      of older people before and after the introduction of consumer directed care (CDC)
      to home care packages (HCP) in Australia. Eligible consumers with a local HCP
      provider were mailed information about the study. Data collection occurred before
      the introduction of CDC and included face-to-face, in-depth interviews, summaries
      of interviews, field notes and reflective journaling. Semi-structured questions
      and 'emotional touchpoints' relating to home care were used to guide the
      interview conversation. Line-by-line data analysis, where significant statements
      were highlighted and clustered to reveal emergent themes, was used. Five older
      people, aged 81 to 91 years, participated in the study. The four emergent themes
      were: seeking quality and reciprocity in carer relationships; patchworking
      services; the waiting game; and technology with utility. Continuity of carers was
      central to the development of a trusting relationship and perceptions of care
      quality among older consumers. Care coordinators and workers should play a key
      role in ensuring older people receive timely information about CDC and their
      rights and responsibilities. Participants' use of contemporary technologies
      suggests opportunities to improve engagement of HCP clients in CDC.

PMID- 28442056
TI  - Corrigendum to: Socioeconomic status as a factor in Indigenous and non-Indigenous
      children with hearing loss: analysis of national survey data.
AB  - In this paper, the association between socioeconomic status and speech, language
      and communication outcomes for primary-school-going children with hearing loss
      using population survey data was analysed. The dataset used for analysis
      consisted of 289973 children in total, of which 3174 children had hearing loss.
      For all children, higher socioeconomic status was positively correlated with
      better speech, language and communication outcomes. A hearing loss was indicated
      for 1% of non-Indigenous children and 4.3% of Indigenous children. Non-Indigenous
      children with hearing loss were found to be fairly evenly distributed by
      socioeconomic status, whereas Indigenous children with hearing loss were found to
      be statistically significantly more likely to be living in the most disadvantaged
      socioeconomic areas. Socioeconomic status was found to affect developmental
      outcomes for all children, regardless of Indigenous and hearing loss status.

PMID- 28442057
TI  - Follicle vascularity coordinates corpus luteum blood flow and progesterone
      production.
AB  - Colour Doppler ultrasonography was used to compare the ability of preovulatory
      follicle (POF) blood flow and its dimensions to predict the size, blood flow and
      progesterone production capability of the subsequent corpus luteum (CL). Cows
      (n=30) were submitted to a synchronisation protocol. Follicles >=7mm were
      measured and follicular wall blood flow evaluated every 12h for approximately 3.5
      days until ovulation. After ovulation, cows were scanned daily for 8 days and
      similar parameters were evaluated for the CL. Blood samples were collected and
      plasma progesterone concentrations quantified. All parameters were positively
      correlated. Correlation values ranged from 0.26 to 0.74 on data normalised to
      ovulation and from 0.31 to 0.74 on data normalised to maximum values.
      Correlations between calculated ratios of both POF and CL in data normalised to
      ovulation and to maximum values ranged from moderate (0.57) to strong (0.87).
      Significant (P<0.0001) linear regression analyses were seen in all comparisons.
      In conclusion, higher correlations were observed between the dimensions of POF
      and/or CL and blood flow of both structures, as well as POF and/or CL blood flow
      with plasma progesterone concentrations of the resultant CL. These findings
      indicate that follicle vascularity coordinates CL blood flow and progesterone
      production in synchronised beef cows.

PMID- 28442058
TI  - Nuclear transfer alters placental gene expression and associated histone
      modifications of the placental-specific imprinted gene pleckstrin homology-like
      domain, family A, member 2 (PHLDA2) in cattle.
AB  - Abnormal placental development is frequent in nuclear transfer (NT) pregnancies
      and is likely to be associated with altered epigenetic reprogramming. In the
      present study, fetal and placental measurements were taken on Day 60 of gestation
      in cows with pregnancies produced by AI, IVF and NT. Placentas were collected and
      subjected to histological evaluation, the expression of genes important in
      trophoblast differentiation and expression of the placental imprinted gene
      pleckstrin homology-like domain, family A, member 2 (PHLDA2), as well as
      chromatin immunoprecipitation (ChIP) for histone marks within the promoter of
      PHLDA2. Fewer binucleated cells were observed in NT cotyledons, followed by IVF
      and AI cotyledons (P<0.05). Expression of heart and neural crest derivatives
      expressed 1 (HAND1), placental lactogen (PL), pregnancy-associated glycoprotein 9
      (PAG-9) and PHLDA2 was elevated in NT cotyledons compared with AI cotyledons.
      Expression of PHLDA2 was higher in IVF than AI samples (P<0.05). ChIP revealed an
      increase in the permissive mark dimethylation of lysine 4 on histone H3
      (H3K4me2), surprisingly associated with the silent allele of PHLDA2, and a
      decrease in the inhibitory mark H3K9me2 in NT samples. Thus, genes critical for
      placental development were altered in NT placentas, including an imprinted gene.
      Allele-specific changes in the permissive histone mark in the PHLDA2 promoter
      indicate misregulation of imprinting in clones. Abnormal trophoblast
      differentiation could have resulted in lower numbers of binucleated cells
      following NT. These results suggest that the altered expression of imprinted
      genes associated with NT are also caused by changes in histone modifications.

PMID- 28442059
TI  - Caudal vena cava progesterone and LH release patterns on Day 14 of gestation in
      primiparous sows.
AB  - The aim of the present study was to explore the relationship between systemic and
      local progesterone secretion and LH pulsatility during implantation in the pig.
      Differences in progesterone concentrations measured locally in the caudal vena
      cava and systemically in the jugular vein were studied in eight primiparous sows
      on Day 14 of pregnancy. LH pulsatility was analysed for its effects on the local
      progesterone-releasing pattern. Mean (+/-s.d.) progesterone concentrations in the
      vena cava (65.5+/-19.8ngmL-1) were approximately double basal concentrations
      (33.6+/-13.1ngmL-1). Basal concentrations of progesterone and LH were calculated
      as the average of the lowest six values. Basal caudal vena cava and mean jugular
      (27.6+/-1.5ngmL-1) progesterone concentrations did not differ significantly. Pre-
      and postprandial jugular progesterone concentrations were significantly different
      in the morning and afternoon (P=0.025 and 0.023). Mean LH ranged from 0.24 to
      0.43ngmL-1 and was approximately double as high as basal LH in individual sows.
      In 60.8% of cases, LH pulses were followed by a progesterone pulse within 1h. In
      conclusion, the present study showed that corpus luteum function appears to
      respond to LH pulsatility on Day 14 of pregnancy. However, the response varies at
      the level of individual sows. In addition, systemic postprandial decreases in
      progesterone were confirmed on Day 14 of pregnancy.

PMID- 28442060
TI  - Kinetic effect of oestrogen on secretion of prostaglandins E2 and F2alpha in
      bovine oviduct epithelial cells.
AB  - This study aimed to investigate the effect of oestrogen on prostaglandin E2
      (PGE2) and prostaglandin F2alpha (PGF2alpha) secretion in bovine oviduct
      epithelial cells. Bovine oviduct epithelial cells were obtained from the lumen of
      fresh bovine oviducts. Quantitative real-time polymerase chain reaction and in
      cell western assays were used to measure PGE2 and PGF2alpha synthase activity and
      enzyme-linked immunosorbent assays were used to detect the concentrations of the
      two prostaglandins in extracellular fluid. We observed that oestradiol caused a
      short-term increase in cyclo-oxygenase-2 (COX-2), which stimulated PGE2 and
      PGF2alpha secretion, and that a subsequent decrease in COX-2 and an increase in
      cyclo-oxygenase-1 (COX-1) produced a high PGE2:PGF2alpha ratio. These findings
      reflect the dynamic change in PGE2 and PGF2alpha levels under the influence of
      oestrogen, which may be essential for fertilisation.

PMID- 28442061
TI  - Effect of docosahexanoic acid on quality of frozen-thawed bull semen in BioXcell
      extender.
AB  - This study was conducted to investigate the effect of docosahexanoic acid (DHA)
      supplementation in BioXcell extender on the quality of frozen-thawed bull semen.
      Twenty-four ejaculates were collected from three bulls (eight from each bull).
      Ejaculates with motility >=70% and normal morphology >=80% were extended into
      BioXcell extender to which 0 (control), 3, 5, 10 or 15ngmL-1 DHA was added. The
      supplemented semen samples were incubated at 37 degrees C for 15min for DHA
      uptake by spermatozoa. Later, samples were cooled for 2h at 5 degrees C and
      packaged into 0.25-mL straws, frozen in liquid nitrogen for 24h and subsequently
      thawed for evaluation. Results are presented as percentages +/- s.e.m.
      Supplementation with DHA at 3ngmL-1 significantly improved sperm functional
      parameters including sperm motility, normal morphology, viability, acrosome
      integrity and membrane integrity when compared with other supplemented groups and
      the control. Lipid peroxidation increased as the incorporation of DHA
      supplementation increased. In conclusion, 3ngmL-1 concentration of DHA resulted
      in superior quality of frozen-thawed bull spermatozoa and is suggested as the
      optimum level of DHA to be added into BioXcell extender.

PMID- 28442062
TI  - Retinoic acid triggers c-kit gene expression in spermatogonial stem cells through
      an enhanceosome constituted between transcription factor binding sites for
      retinoic acid response element (RARE), spleen focus forming virus proviral
      integration oncogene (SPFI1) (PU.1) and E26 transformation-specific (ETS).
AB  - Restricted availability of retinoic acid (RA) in the testicular milieu regulates
      transcriptional activity of c-kit (KIT, CD117), which aids in the determination
      of spermatogonial stem-cell differentiation. The effect of RA on c-kit has been
      reported previously, but its mode of genomic action remains unresolved. We
      studied the molecular machinery guiding RA responsiveness to the c-kit gene using
      spermatogonial stem-cell line C18-4 and primary spermatogonial cells. A novel
      retinoic acid response element (RARE) positioned at -989 nucleotides upstream of
      the transcription start site (TSS) was identified, providing a binding site for a
      dimeric RA receptor (i.e. retinoic acid receptor gamma (RARgamma) and retinoic X
      receptor). RA treatment influenced c-kit promoter activity, along with endogenous
      c-kit expression in C18-4 cells. A comprehensive promoter deletion assay using
      the pGL3B reporter system characterised the region spanning -271bp and -1011bp
      upstream of the TSS, which function as minimal promoter and maximal promoter,
      respectively. In silico analysis predicted that the region -1011 to +58bp
      comprised the distal enhancer RARE and activators such as spleen focus forming
      virus proviral integration oncogene (SPFI1) (PU.1), specificity protein 1 (SP1)
      and four E26 transformation-specific (ETS) tandem binding sites at the proximal
      region. Gel retardation and chromatin immunoprecipitation (ChIP) assays showed
      binding for RARgamma, PU.1 and SP1 to the predicted consensus binding sequences,
      whereas GABPalpha occupied only two out of four ETS binding sites within the c
      kit promoter region. We propose that for RA response, an enhanceosome is
      orchestrated through scaffolding of a CREB-binding protein (CBP)/p300 molecule
      between RARE and elements in the proximal promoter region, controlling germ-line
      expression of the c-kit gene. This study outlines the fundamental role played by
      RARgamma, along with other non-RAR transcription factors (PU.1, SP1 and
      GABPalpha), in the regulation of c-kit expression in spermatogonial stem cells in
      response to RA.

PMID- 28442063
TI  - Peri-ovulatory endocrine regulation of the prostanoid pathways in the bovine
      uterus at early dioestrus.
AB  - We hypothesised that different endocrine profiles associated with pre-ovulatory
      follicle (POF) size would impact on uterine prostanoid pathways and thereby
      modulate the histotroph composition. Beef cows (n=15 per group) were hormonally
      manipulated to have small (SF-SCL group) or large (LF-LCL group) pre-ovulatory
      follicles (POF) and corpora lutea (CL). Seven days after induction of ovulation,
      animals were slaughtered and uterine tissues and flushings were collected for
      quantification of prostanoids. The POF and CL size and the circulating
      progesterone concentrations at Day 7 were greater (P<0.05) in the LF-LCL cows
      than in the SF-SCL group, as expected. The abundance of 5 out of 19 genes
      involved in prostanoid regulation was different between groups. Transcript
      abundance of prostaglandin F2alpha, E2 and I2 synthases was upregulated (P<0.05)
      and phospholipase A2 was downregulated (P<0.05) in endometrium of the LF-LCL
      group. No difference (P>0.1) in prostanoid concentrations in the endometrium or
      in uterine flushings was detected between groups. However, prostaglandin F2alpha
      and E2 concentrations in the uterine flushings were positively correlated with
      the abundance of transcripts for prostaglandin endoperoxide synthase 2 (0.779 and
      0.865, respectively; P<0.002). We conclude that endometrial gene expression
      related to prostanoid synthesis is modulated by the peri-ovulatory endocrine
      profile associated with POF size, but at early dioestrus differences in
      transcript abundance were not reflected in changes in prostanoid concentrations
      in the uterine tissue and fluid.

PMID- 28442064
TI  - Nutrient restriction in early ovine pregnancy stimulates C-type natriuretic
      peptide production.
AB  - C-type natriuretic peptide (CNP), a paracrine growth factor promoting
      vasodilation and angiogenesis, is upregulated in human and ovine pregnancy in
      response to vascular stress or nutrient restriction (NR) in late gestation.
      Postulating that maternal plasma CNP products are increased by modest NR (50% of
      metabolisable energy requirement) early in pregnancy, and further enhanced by
      litter size, we studied serial changes of maternal plasma CNP in pregnant ewes
      receiving a normal (NC, n=12) or restricted (NR, n=13) diet from Day 30 to Day 93
      or 94 of gestation. Liveweight of NR ewes was 10kg less than that of NC ewes at
      slaughter. Plasma CNP products increased progressively after Day 40 and were
      higher in NR (P<0.05) ewes after Day 60; they were also enhanced by litter size
      (P<0.01) and were positively associated with increased placental efficiency. In
      contrast, whereas fetal and placental weight were reduced by NR, fetal plasma CNP
      products (Day 93/94) were not affected. We conclude that increases in CNP during
      rapid placental growth are further enhanced by both increasing nutrient demands
      and by reduced supply, presumably as part of an adaptive response benefitting
      placental-fetal exchange.

PMID- 28442065
TI  - The morphological and functional development of the stria vascularis in miniature
      pigs.
AB  - The purpose of this study was to examine the morphological and functional
      development of the lateral wall of the scala media of the cochlea in miniature
      pigs; light and transmission electron microscopy and electrophysiology were used
      for this purpose. We showed that the lateral wall of the scala media of the
      cochlea appears at embryonic Day 21 (E21) when the cochlear duct begins to form.
      From E28 to E49, the lateral wall can be distinguished according to its position
      along the cochlea. At E56, cells in the lateral wall begin to differentiate into
      three different types. At E70, three cell types, marginal, intermediate and
      basal, can be clearly distinguished. At E91, the stria vascularis is adult-like
      and the organ of Corti is also morphologically mature. The average endocochlear
      potential measured from the second turn of the cochlea (at E98, postnatal Day 1
      (P1), P13 and P30) was 71.4+/-2.5 (n=7), 78.8+/-1.5 (n=10), 77.3+/-2.3 (n=10) and
      78.0+/-2.1 mV (n=10), respectively. Our results suggest that in miniature pigs
      the stria vascularis develops during the embryonic period, concurrent with
      maturation of the organ of Corti. The magnitude of the endocochlear potential
      reached its mature level when the stria vascularis was morphologically adult-like
      at E98. These findings provide a morphological and functional basis for future
      animal studies using the miniature pig model concerning the pathogenesis of
      various inner-ear diseases.

PMID- 28442066
TI  - Characterisation and cryopreservation of the ovarian preantral follicle
      population from Spix's yellow-toothed cavies (Galea spixii Wagler, 1831).
AB  - The aim of the present study was to characterise the ovarian preantral follicle
      (PF) population and to establish a solid surface vitrification (SSV) process
      using dimethyl sulfoxide (DMSO) as a cryoprotectant for preservation of ovarian
      tissue from yellow-toothed cavies (Galea spixii). Ovaries were fixed for PF
      population analysis or were subjected to the SSV process. The mean (+/- s.e.m.)
      PF population per ovarian pair was estimated to be 416.0+/-342.8. There were
      140.0+/-56.0 (63.4%) and 125.0+/-58.0 (64.0%) primary follicles on the right and
      left ovaries, respectively. The proportion of this follicle category was
      significantly greater than that of other follicle categories (P<0.05). The
      diameter of follicles (123.7+/-18.3um), oocytes (50.1+/-5.0um) and nuclei
      (14.27+/-2.01um) was larger for secondary ones when compared with other PFs
      categories. Most PFs were morphologically normal (94.6%), with light microscopy
      identifying only a few atretic follicles (5.4%). After SSV, there was a reduction
      in the proportion of morphologically normal PFs compared with the non-vitrified
      group (69.5% vs 91.2%, respectively). Transmission electron microscopy revealed
      preservation of oocytes and granulosa cell membranes and the morphological aspect
      of follicles; the primary change observed in some vitrified PFs was the presence
      of vacuoles in the oocytes and granulosa cells cytoplasm and turgid mitochondria.
      In conclusion, the present study provides an estimative and characterization for
      the PF population in ovaries of G. spixii. Moreover, we report its PFs
      cryopreservation using an SSV process.

PMID- 28442067
TI  - Meta-analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass
      Grafting in Left Main Coronary Artery Disease.
AB  - Despite the increase in use of percutaneous coronary intervention (PCI) in left
      main coronary disease, its efficacy compared with coronary artery bypass grafting
      (CABG) is unclear. We performed a meta-analysis of randomized controlled trials
      to assess the optimal revascularization strategy. Our search yielded 8 studies
      reporting relevant outcomes that were pooled using the inverse variance method,
      and the hazard ratio (HR) was calculated. The primary outcome was all-cause
      mortality, myocardial infarction (MI), or stroke (major adverse cardiac events
      [MACE]), and the secondary outcome was death/MI/stroke/repeat revascularization
      (expanded MACE). Differences in outcomes classified by follow-up duration (early:
      0 to 1 year; late: 3 to 5 years) or anatomical complexity of coronary artery
      disease (SYNTAX score) were investigated. Our results suggest no difference in
      either early or late MACE (early: HR 0.81; 95% confidence interval [CI] 0.63 to
      1.05; late: HR 1.12; 95% CI 0.80 to 1.56) or expanded MACE (early: HR 1.03; 95%
      CI 0.69 to 1.52; late: HR 1.16; 95% CI 0.95 to 1.43) between the 2 groups. There
      was an increased risk of expanded MACE with a high SYNTAX score for PCI (HR 1.47;
      95% CI 1.13 to 1.92) at late follow-up. There were comparable rates of all-cause
      mortality and nonprocedural MI between the 2 groups with increased rates of
      repeat revascularization with PCI throughout the follow-up and higher rates of
      stroke with coronary artery bypass grafting early in the follow-up period. In
      conclusion, our analysis suggests that CABG may be preferable in patients with
      left main disease and high SYNTAX scores, assuming they are at low surgical risk,
      and PCI may be an acceptable alternative in patients with low-intermediate SYNTAX
      scores.

PMID- 28442068
TI  - Intraoperative nerve monitoring in laryngotracheal surgery.
AB  - Laryngotracheal surgery has an inherent risk of injury to the recurrent laryngeal
      nerves (RLN). These complications go from minor dysphonia to even bilateral vocal
      cord paralysis. The intraoperative neuromonitoring of the RLN was developed in
      the field of thyroid surgery, in order to preserve nerve and vocal cord function.
      However, tracheal surgery requires in-field intubation of the distal trachea,
      which limits the use of nerve monitoring using conventional endotracheal tube
      with surface electrodes. Given these challenges, we present an alternative method
      for nerve monitoring during laryngotracheal surgery through the insertion of
      electrodes within the endolaryngeal musculature by bilateral puncture.

PMID- 28442069
TI  - Reassurance for patients with non-specific conditions - a user's guide.
AB  - INTRODUCTION: Reassurance is the removal of fears and concerns about illness. In
      practice reassurance for non-specific conditions, where a diagnosis is unclear or
      unavailable, is difficult and can have unexpected effects. Many clinical
      guidelines for non-specific conditions such as low back pain recommend
      reassurance. Until recently, there was little evidence on how to reassure
      patients effectively. RESULTS: High distress causes patients to consult more
      often for low back pain. To reduce distress, clinicians should provide structured
      education, which is effective in the short- and long-term. A newly developed
      online prognostic tool has the potential to improve the quality of reassurance
      and reduce the number of inappropriate interventions provided for low back pain.
      CONCLUSION: Targeted reassurance, including enhanced, prognosis-specific
      education, could optimize reassurance and possibly prevent disabling symptoms.

PMID- 28442070
TI  - Comparing airways clearance techniques in chronic obstructive pulmonary disease
      and bronchiectasis: positive expiratory pressure or temporary positive expiratory
      pressure? A retrospective study.
AB  - BACKGROUND: Airway clearance techniques include positive expiratory pressure,
      commonly used in our clinical practice, and a recently introduced temporary
      positive expiratory pressure device called UNIKO(r). It is unclear which one
      provides the best benefit to patients. OBJECTIVES: The aim of this observational
      4-year study was to retrospectively compare the efficacy of and specific
      indications for temporary positive expiratory pressure compared to positive
      expiratory pressure in a standard rehabilitation program. METHOD: We
      retrospectively collected data from 162 subjects (107 males, mean age 70+/-9
      years, 97 with primary diagnosis of chronic obstructive pulmonary disease, 65
      with bronchiectasis), 51 treated with temporary positive expiratory pressure and
      111 with positive expiratory pressure. RESULTS: Subjects showed significant
      improvement in ratio of partial pressure arterial oxygen and fraction of inspired
      oxygen (p<0.001), forced vital capacity, forced expiratory volume in one second,
      peak expiratory flow, arterial oxygen saturation, and partial pressure arterial
      oxygen with no significant difference between positive expiratory pressure and
      temporary positive expiratory pressure groups apart from forced expiratory flow,
      which increased only in the positive expiratory pressure group. Evaluating
      specific subgroups, temporary positive expiratory pressure was more effective
      than positive expiratory pressure in improving gas transfer in subjects with
      emphysema and in those on oxygen therapy, as the effective supplement oxygen flow
      decreased significantly (p=0.034 and 0.046 respectively for temporary positive
      expiratory pressure vs. positive expiratory pressure). In subjects on mechanical
      ventilation, positive expiratory pressure was superior to temporary positive
      expiratory pressure in increasing forced expiratory flow (p=0.018). CONCLUSION:
      The physiological parameters of both groups improved significantly and similarly.
      Subgroup analysis suggests that temporary positive expiratory pressure could
      provide some advantage to subjects with emphysema and those on oxygen therapy,
      while positive expiratory pressure would benefit patients on mechanical
      ventilation. Randomized clinical trials are necessary to confirm our preliminary
      results indicating that different subgroups/phenotypes can benefit more from one
      type of treatment.

PMID- 28442071
TI  - Observational practice of incentive spirometry in stroke patients.
AB  - BACKGROUND: Stroke may lead to several health problems, but positive effects can
      be promoted by learning to perform physical therapy techniques correctly.
      OBJECTIVE: To compare two different types of observational practice (video
      instructions and demonstration by a physical therapist) during the use of
      incentive spirometry (IS). METHOD: A total of 20 patients with diagnosis of
      stroke and 20 healthy individuals (56+/-9.7 years) were allocated into two
      groups: one with observational practice with video instructions for the use of IS
      and the other with observational practice with demonstration by a physical
      therapist. Ten attempts for the correct use of IS were carried out and the number
      of errors and the magnitude of response were evaluated. The statistic used to
      compare the results was the three-way ANOVA test. RESULTS: The stroke subjects
      showed less precision when compared to the healthy individuals (mean difference
      1.80+/-0.38) 95%CI [1.02-2.52], p<0.0001. When the type of practice was analyzed,
      the stroke subjects showed more errors with the video instructions (mean
      difference 1.5+/-0.5, 95%CI [0.43-2.56] (p=0.08)) and therapist demonstration
      (mean difference 2.40+/-0.52, 95%CI [1.29-3.50] (p=0.00)) when compared to the
      healthy individuals. CONCLUSION: The stroke subjects had a worse performance in
      learning the use of volume-oriented incentive spirometry when compared to healthy
      individuals; however, there was no difference between the types of observational
      practice, suggesting that both may be used to encourage the use of learning IS in
      patients with stroke.

PMID- 28442072
TI  - Predictive equations for maximal respiratory pressures of children aged 7-10.
AB  - BACKGROUND: Measurements of respiratory muscle strength are widely used for
      assessment in children; however, clearly defined predictive equations for the
      Brazilian pediatric population have yet to be established. OBJECTIVE: To
      determine the prediction equations for maximal respiratory pressures in healthy
      children. METHOD: Cross-sectional observational study with normal-weight students
      aged 7-10 years (n=399, 198 boys) with health attested by the (International
      Study of Asthma and Allergies in Childhood) questionnaire and medical history.
      Biometric data were evaluated (weight, height, and body mass index) as
      predictors. Spirometry and maximal expiratory pressure values were measured
      according to the recommendations of the American Thoracic Society. To verify data
      normality, the Shapiro-Wilk test was applied, and Pearson's test was used to
      verify the correlation between variables. The models were developed using simple
      linear regression and multivariate analyses. For all tests, the significance
      level was p<0.05. RESULTS: Boys showed higher values of maximal respiratory
      pressures than girls, both increasing with age. For boys, these values had
      moderate correlation with age, weight, and height and weak correlation with body
      mass index. For girls, maximum inspiratory pressure had a weak correlation with
      age and moderate correlation with biometric data. Maximum expiratory pressure had
      a moderate correlation with age and biometric measures. The best predictive
      models were found in boys: Log(MIP)=1.577+0.006*weight (kg) (R2aj=14.1%) and
      Log(MEP)=1.282+0.409*height (m) (R2aj=13.9%); and for girls:
      Log(MIP)=1.548+0.006*weight (kg) (R2aj=15.0%) and Log(MEP)=1.524+0.012*age
      (years)+0.005*weight (kg) (R2aj=21.6%). CONCLUSION: Prediction equations for
      maximal respiratory pressures were developed for boys and girls. The biometric
      measurements were shown to have a weak influence on the results.

PMID- 28442073
TI  - Implications of pain in functional activities in immediate postpartum period
      according to the mode of delivery and parity: an observational study.
AB  - OBJECTIVES: To identify women's complaints about pain in the immediate postpartum
      of vaginal delivery and cesarean section; to measure the intensity of pain in
      postpartum women at rest and with selected movements and to compare the activity
      limitations in relation to the mode of delivery and parity. METHOD:
      Observational, descriptive, cross-sectional study. Eighty-six women, in the
      immediate postpartum period after vaginal delivery (n=43) and cesarean section
      (n=43), were evaluated for physical discomforts and their difficulty in
      performing functional activities. RESULTS: Abdominal pain (mean differences=
      39.5%; 95% CI=-57.3 to -21.8%), neck pain (mean differences=-16.3%; 95% CI=-32.3
      to -0.3%) and edema (mean differences=-41.4%; 95% CI=-63.3 to -20.4%) were
      reported of cesarean women postpartum. Perineal pain (p<0.05) was reported in
      vaginal delivery women postpartum. Postpartum pain was more severe during
      movement after cesarean section (p<0.05) resulting in pain during the activities
      of sitting down (mean differences=-30.2%; 95% CI=-50.7 to -9.8%), standing up
      from a sitting position (mean differences=-46.5%; 95% CI=-65.0 to -28.0%),
      walking (mean differences=-44.2%; 95% CI=-65.2 to -23.1%), lying down (mean
      differences=-32.6%; 95% CI=-54.9 to -10.3%) and taking a bath (mean differences=
      24.0%; 95% CI=-43.1 to -5.0%). Correspondence analysis found no association
      between parity and functional limitations. CONCLUSION: The highest number of
      complaints was associated with movement activities and cesarean section
      postpartum. There was no relationship between functional limitations and parity
      in this study.

PMID- 28442074
TI  - Predictors of perceived barriers to physical activity in the general adult
      population: a cross-sectional study.
AB  - BACKGROUND: The perception of personal barriers to physical activity varies
      according to the sociodemographic characteristics of individuals. OBJECTIVE: To
      determine the predictors of the perception of barriers to physical activity in
      the adult population. METHOD: A cross-sectional study with 1066 adult women and
      1036 adult men. The sociodemographic variables (age, gender, marital status,
      socioeconomic level, level of education), the perception of barriers that do not
      allow performance of physical activity (i.e. lack of time, social support,
      energy, motivation, skill, resources, and fear of injury during practice); and
      the level of physical activity through the International Physical Activity
      Questionnaire in its short-form version were evaluated. RESULTS: Individuals from
      low socioeconomic level (1 and 2) have higher risks of perceiving barriers such
      as lack of motivation [OR 1.76 (95% CI (1.4-2.1))] and lack of resources [OR 1.37
      (95% CI (1.1-1.6))]; individuals with partners did not perceive the lack of
      social support [OR 0.29 (95% CI (0.2-0.4))] and lack of motivation [OR 0.54 (95%
      CI (0.4-0.7))] as barriers to physical activity. Individuals with low schooling
      perceived lack of social support [OR 3.81 (95% CI (3-4.7))], lack of resources
      [OR 2.78 (95% CI (2.2-3.3))], and fear of injury [OR 2.70 (95% CI (2.2-3.3))] as
      barrier to physical activity. CONCLUSION: Factors such as socioeconomic level,
      marital status, level of education, and self-perception of health are predictors
      of barriers to physical activity.

PMID- 28442075
TI  - Passive stiffness of the ankle and plantar flexor muscle performance after
      Achilles tendon repair: a cross-sectional study.
AB  - BACKGROUND: Deficits in ankle muscle strength and ankle stiffness may be present
      in those subjects who underwent surgical treatment for an Achilles tendon
      rupture. The presence of these long-term deficits may contribute to a lower
      performance during daily activities and may be linked to future injuries.
      OBJECTIVE: To compare the ankle passive stiffness and the plantar flexor muscle
      performance in patients who underwent unilateral surgical treatment of Achilles
      tendon rupture with nonsurgical subjects. METHOD: Twenty patients who underwent
      unilateral surgical treatment of Achilles tendon rupture [surgical (SU) group],
      and twenty nonsurgical subjects [non-surgical (NS) group] participated in this
      study. The ankle passive stiffness was evaluated using a clinical test. The
      concentric and eccentric plantar flexors performance (i.e. peak torque and work)
      was evaluated using an isokinetic dynamometer at 30 degrees /s. RESULTS: The
      surgical ankle of the surgical group presented lower stiffness compared to the
      non-surgical ankle (mean difference=3.790; 95%CI=1.23-6.35) and to the non
      dominant ankle of the non-surgical group (mean difference=-3.860; 95%CI=-7.38 to 
      0.33). The surgical group had greater absolute asymmetry of ankle stiffness (mean
      difference=-2.630; 95%CI=-4.61 to -0.65) and greater absolute asymmetry of
      concentric (mean difference=-8.3%; 95%CI=-13.79 to -2.81) and eccentric (mean
      difference=-6.9%; 95%CI=-12.1 to -1.7) plantar flexor work compared to non
      surgical group. There was no other difference in stiffness and plantar flexor
      performance. CONCLUSION: Patients who underwent surgical repair of the Achilles
      tendon presented with long-term (1 year or more) deficits of ankle stiffness and
      asymmetries of ankle stiffness and plantar flexor work in the affected ankle
      compared to the uninjured side in the surgical group and both sides on the
      nonsurgical group.

PMID- 28442076
TI  - Exercise training for people following curative intent treatment for non-small
      cell lung cancer: a randomized controlled trial.
AB  - OBJECTIVE: In people following curative intent treatment for non-small cell lung
      cancer, to investigate the effects of supervised exercise training on exercise
      capacity, physical activity and sedentary behavior, peripheral muscle force,
      health-related quality of life, fatigue, feelings of anxiety and depression, and
      lung function. METHOD: This pilot randomized controlled trial included
      participants 6-10 weeks after lobectomy for non-small cell lung cancer or, for
      those who required adjuvant chemotherapy, 4-8 weeks after their last cycle.
      Participants were randomized to either 8 weeks of supervised exercise training
      (exercise group) or 8 weeks of usual care (control group). Prior to and following
      the intervention period, both groups completed measurements of exercise capacity,
      physical activity and sedentary behavior, quadriceps and handgrip force, HRQoL,
      fatigue, feelings of anxiety and depression, and lung function. Intention-to
      treat analysis was undertaken. RESULTS: Seventeen participants (mean age 67, SD=9
      years; 12 females) were included. Nine and eight participants were randomized to
      the exercise and control groups, respectively. Four participants (44%) adhered to
      exercise training. Compared with any change seen in the control group, those in
      the exercise group demonstrated greater gains in the peak rate of oxygen
      consumption (mean difference, 95% confidence interval for between-group
      difference: 0.19 [0.04-0.33]Lmin-1) and 6-minute walk distance (52 [12-93]m). No
      other between-group differences were demonstrated. CONCLUSIONS: In people
      following curative intent treatment for non-small cell lung cancer, 8 weeks of
      supervised exercise training improved exercise capacity, measured by both
      laboratory- and field-based exercise tests. These results suggest that this
      clinical population may benefit from attending exercise training programs.

PMID- 28442077
TI  - Construct and discriminant validity of STarT Back Screening Tool - Brazilian
      version.
AB  - BACKGROUND: The STarT Back Screening Tool (SBST) was developed to stratify low
      back pain patients according to their risk of future physical disability so that
      prognostic subgroups can receive matched treatments in primary care. OBJECTIVE:
      To measure the construct and discriminative validity of the SBST-Brazil
      questionnaire. METHOD: A hundred and fifty one patients were recruited to test
      the construct and discriminative validity comparing the SBST-Brazil to the
      Brazilian Version of the Oswestry Disability Index (ODI), Roland Morris
      Disability Questionnaire (RMDQ) and Fear-Avoidance Beliefs Questionnaire-Work
      (FABQ-W) and Physical Activity (FABQ-PA) subscales at baseline. Spearman's rank
      order correlation and area under the curve (AUC) derived from receiver operating
      curves (ROC) for total scores and psychosocial subscale score of the SBST-Brazil
      were used for construct and discriminant validity analysis, respectively.
      RESULTS: The SBST-Brazil total and psychosocial subscale scores had good and
      moderate correlation with ODI (r=0.61; r=0.56, respectively) and good with RMDQ
      (r=0.70; r=0.64, respectively). Both scores of the SBST-Brazil total and
      psychosocial subscale correlated weakly and moderately with the FABQ-PA (r=0.28;
      r=0.34, respectively) and weakly with the FABQ-W (r=0.18; r=0.20, respectively).
      The discriminant validity with AUCs for the total and psychosocial subscale
      scores against reference standard ranged from 0.66 for kinesiophobia to 0.88 for
      disability. CONCLUSION: The SBST-Brazil showed a moderate to good correlation
      with the disability tools, but a weak correlation with fear-avoidance beliefs.
      The results of discriminant validity suggest that SBST-Brazil is able to
      discriminate low back pain patients with disability and fear-avoidance beliefs.

PMID- 28442079
TI  - Correction.

PMID- 28442078
TI  - Knee pain in adolescents: prevalence, risk factors, and functional impairment.
AB  - OBJECTIVE: To investigate knee pain prevalence, associated factors, and
      functional impairment among adolescents. METHOD: This was a cross-sectional study
      conducted between May and June 2014 with a random sample of 619 adolescents aged
      between 10 and 17 years. Knee pain prevalence was investigated using the Nordic
      Questionnaire for Osteomuscular Symptoms and a number of independent variables
      (demographic data, nutritional status, form of carrying backpacks, and pain
      during and after walking) obtained by self-report questionnaires. Physical
      impairment of the knee was assessed using the Brazilian version of the Knee
      injury and Osteoarthritis Outcome Score questionnaire. Poisson regression
      analysis was used to estimate the ratios of crude and adjusted knee pain
      association with the investigated factors. ANOVA and Kruskal-Wallis tests were
      used to compare median functional impairment. RESULTS: Knee pain prevalence over
      the last 7 days was 22.6%. Factors having significant association with the
      outcome were: being between 12 and 14 years old (PR: 1.67; 95% CI: 1.07-2.58;
      p<0.01), being between 15 and 17 years old (PR: 2.44; 95% CI: 1.51-3.94; p=0.01),
      and not doing physical education at school (PR: 0.54; 95% CI: 0.35-0.82; p=0.01).
      Total functional capacity among adolescents with pain was significantly lower
      among girls (68.7 points; PD+/-15.1) when compared with boys (74.3 points; PD+/
      12.7) (p=0.02). The mean value of disabling pain was lower (55.1 points; PD+/
      12.3) among adolescents who were physically active in their leisure time compared
      to those who were insufficiently active (60.4 points; PD+/-12.4) (p=0.02).
      CONCLUSION: The results of this study show that knee pain among adolescents with
      no previous history should be investigated, particularly among older adolescents
      who do not have physical education at school, since it is highly prevalent and
      can result in functional impairment. Regarding functionality, more attention
      should be given to girls and adolescents who were physically active in their
      leisure time.

PMID- 28442080
TI  - Male With Chest Pain and Lightheadedness.

PMID- 28442081
TI  - Unresponsive Male.

PMID- 28442082
TI  - Female With Pain in the Right Shoulder and Chest.

PMID- 28442083
TI  - Young Infant With Vomiting.

PMID- 28442084
TI  - American Board of Emergency Medicine Report on Residency and Fellowship Training
      Information (2016-2017).
AB  - The American Board of Emergency Medicine (ABEM) gathers extensive background
      information on emergency medicine residency programs and the residents training
      in those programs. We present the 2017 annual report on the status of US
      emergency medicine training programs.

PMID- 28442085
TI  - SIM Serendipity.

PMID- 28442086
TI  - I Recently Went to a Funeral.

PMID- 28442087
TI  - Amazing and Awesome Rounds.

PMID- 28442088
TI  - On Resolution 22.

PMID- 28442089
TI  - X Marks the Spot (or Does It?): Ultrasonography-Assisted Site Marking for Lumbar
      Puncture in Children: May 2017 Annals of Emergency Medicine Journal Club.

PMID- 28442090
TI  - Adolescent Female With Headache and Nausea.

PMID- 28442091
TI  - Woman With Severe Headache.

PMID- 28442092
TI  - Postural Headache? It's Not a Tumor!

PMID- 28442093
TI  - Earlobe Crease in Patient With Chest Pain.

PMID- 28442094
TI  - Elderly Male With Neck Stiffness and Fever.

PMID- 28442095
TI  - Diabetic Ketoacidosis and Acute Pancreatitis: Serious Adverse Effects of
      Everolimus.

PMID- 28442096
TI  - Ketamine Causing Apnea?

PMID- 28442097
TI  - In reply.

PMID- 28442098
TI  - Are You Paying Attention? Related Guidance on How Concepts of Attention May
      Inform Effective Time Sharing of Tasks in Emergency Medicine.

PMID- 28442100
TI  - Correction.

PMID- 28442099
TI  - In reply.

PMID- 28442101
TI  - Ultrasound Guidelines: Emergency, Point-of-Care and Clinical Ultrasound
      Guidelines in Medicine.

PMID- 28442102
TI  - Adolescent Female With Abdominal Pain.

PMID- 28442103
TI  - Man With Painless Oral Lesions.

PMID- 28442104
TI  - Zika virus infection and its emerging trends in Southeast Asia.
AB  - Zika virus is a mosquito-borne flavivirus that represents a public health
      emergency at the ongoing epidemic. Previously, this rare virus was limited to
      sporadic cases in Africa and Asia until its emergence in Brazil, South America in
      2015, where it rapidly spread throughout the world. Recently, a high number of
      cases were reported in Singapore and other Southeast Asia countries. A
      combination of factors explains the current Zika virus outbreak although it is
      highly likely that the changes in the climate and high frequency of travelling
      contribute to the spread of Aedes vector carrying the Zika virus mainly to the
      tropical climate countries such as the Southeast Asia. The Zika virus is known to
      cause mild clinical symptoms similar to those of dengue and chikungunya and
      transmitted by different species of Aedes mosquitoes. However, neurological
      complications such as Guillain-Barre syndrome in adults, and congenital
      anomalies, including microcephaly in babies born to infected mothers, raised a
      serious concern. Currently, there is no specific antiviral treatment or vaccine
      available for Zika virus infection. Therefore, international public health
      response is primarily focused on preventing infection, particularly in pregnant
      women, and on providing up-to-date recommendations to reduce the risk of non
      vector transmission of Zika virus.

PMID- 28442105
TI  - Towards development of a universal dengue vaccine - How close are we?
AB  - Dengue has been ranked as one of the top emerging diseases in Asia and Latin
      America. Current epidemiological data may not even reflect the true burden of
      disease due to under-reported figures. Vector control programmes have failed to
      contain the disease and worst of all, no specific treatment is available at the
      moment. Thereby, this pushes the demand for a dengue vaccine as a long-term
      protective approach. Despite there are numerous vaccine candidates ahead, they
      could be held back by different aspects in promoting vaccine implementation.
      Particularly for developing nations, logistics and cost are the major hurdles
      that need to be addressed in order to provide a quick yet affordable medical
      relief. As an alternative, plant-based vaccine production system is able to offer
      an attractive prospect given to its advantages of biocontainment warranty, low
      operation cost, rapid scalability and logistics flexibility. Researches that have
      embarked on this scope are laid out and reviewed in terms of the feasibility of
      plant system to serve as a biofactory for dengue vaccine.

PMID- 28442106
TI  - Medicinal and biological values of Callistemon viminalis extracts: History,
      current situation and prospects.
AB  - Callistemon viminalis (C. viminalis) is a plant that has been reported to have
      various medicinal values such as antibacterial, antifungal, antioxidant
      activities and other pharmaceutical and insecticidal properties. This review
      covers the potentials, applications and properties of different extracts from
      different parts (branches, flowers, fruits, bark, leaves) of C. viminalis.
      Furthermore, the chemical structures of the bioactive compounds were reported for
      biological activities. All the results supported the traditional uses of C.
      viminalis in folk medicine. In addition, some researches supported the use of C.
      viminalis extracts for the preparation of metal oxide nanoparticles.

PMID- 28442107
TI  - In vitro and in vivo investigation of natural compounds from seed extract of
      Mucuna pruriens lacking l-DOPA for the treatment of erectile dysfunction.
AB  - OBJECTIVE: To investigate the biological effects of the Mucuna pruriens (M.
      pruriens) seed extracts that lacked l-DOPA, which was formerly reported as the
      active ingredient, on erectile dysfunction (ED) both in vitro and in vivo.
      METHODS: Seed of M. pruriens plant that cultivated in Mae Taeng District, Chiang
      Mai Province, Thailand, was collected. Component of its seeds were extracted and
      isolated into 2 fractions using methanol, polar and nonpolar. Each fraction was
      investigated for phytochemicals using gas chromatography and mass spectroscopy
      and was screened for biological activity in vitro using three different cell
      lines. The most biological active fraction was used to treat both streptozotocin
      (STZ)-induced diabetes mellitus-erectile dysfunction (DM-ED) male Wistar rats and
      normal rats (n = 6 per groups) to compare the effect on sexual behavior
      parameters, including number of intromission, mounting and ejaculation, with that
      of rats given Sildenafil by individually pairing with their female counterparts.
      Penile tissues and serums were collected to determine histological structure,
      related gene expression and biomolecules. RESULTS: The phytochemicals of the
      polar fraction were possibly catechol and its derivatives plus polyphenols,
      whereas the nonpolar fraction consisted of lipid derivatives. l-DOPA was not
      detected in either of the extracts. The polar fraction was able to up-regulate
      the expression of ED-related genes including eNOS and nNOS in vitro which
      subsequently promotes nitric oxide production and maintains intracellular cyclic
      guanosine monophosphate levels. When administrated to DM-ED rats, the polar
      extract significantly improved all sexual behavior parameters in DM-ED rats
      compared to untreated group (18.3 +/- 1.8 to 10.8 +/- 2.9 for intromission, 9.8
      +/- 2.2 to 5.7 +/- 1.3 for mounting, and 1.8 +/- 0.6 to 0.2 +/- 0.4 for
      ejaculation). That effect might due to the ability of the extract to stimulate
      the expression of eNOS and nNOS which results in nitric oxide production and
      subsequently maintains cyclic guanosine monophosphate levels in penile tissue.
      Moreover, this extract may also prevent penile tissue deterioration due to
      diabetes. CONCLUSIONS: The polar extract of M. pruriens seed can be used for ED
      therapy, especially in patients with metabolic diseases including diabetes. The
      action of the extract might be due to catechol and its derivatives and
      polyphenols.

PMID- 28442108
TI  - Effect of Egyptian propolis on cryptosporidiosis in immunosuppressed rats with
      special emphasis on oocysts shedding, leukogram, protein profile and ileum
      histopathology.
AB  - OBJECTIVES: To investigate the activity of Egyptian propolis extracts (ethanol
      and water) on cryptosporidiosis in experimentally infected dexamethasone
      immunosuppressed rats. METHODS: A total of 180 male rats (190-220) g BWt were
      randomly divided into 9 equal groups (G1-G9). Groups of rats were kept as (G1):
      normal control, (G2-G9): immunosuppressed with dexamethasone and (G3-G9):
      infected with Cryptosporidium oocysts. Rats from (G4-G9) were given orally
      ethanol and water extract of propolis (at a dose of 50 mg/kg BWt) and
      nitazoxanide (standard anti-cryptosporidial drug at a dose of 100 mg/kg BWt) to
      infected rats with different regimes. Faecal pellets were collected from all
      groups to monitor oocysts shedding from the 2nd to the 15th day post infection.
      At the end of the experiment, blood was collected from all groups for
      determination of leukogram and serum proteins. Ileum specimens were also examined
      histopathologically. RESULTS: The highest reduction of oocysts shedding in faecal
      samples was 88% in rats prophylactically treated with propolis ethanol extract at
      the 4th dpi, and in rats prophylactically treated with water extract of propolis,
      was 91% at the 6th dpi. There was a marked increase in neutrophils count and
      alpha2- and beta-globulins levels in infected rats treated with both extracts,
      while a significant decrease was detected in lymphocytes compared to the infected
      non treated group. beta-Globulin level markedly increased in the rats
      administered nitazoxanide. Histopathological changes were observed in the ileum
      of rats infected with Cryptosporidium. CONCLUSIONS: Egyptian propolis extracts
      have an activity on cryptosporidiosis in rats. Moreover, propolis modulated the
      immunity in dexamethasone-immunosuppressed rats.

PMID- 28442109
TI  - Potential antioxidant properties and hepatoprotective effects of Juniperus
      phoenicea berries against CCl4 induced hepatic damage in rats.
AB  - OBJECTIVE: To investigate the antioxidant and hepatoprotective properties of
      Juniperus phoenicea (J. phoenicea) berries against CCl4-induced oxidative damage
      in rats. METHODS: Hepatotoxicity was induced in albino Wistar rats by single dose
      of CCl4 dissolved in olive oil (1 mL/kg BW, 1/1 in olive oil, i.p.). Aqueous
      extract of J. phoenicea berries (AEJP) was administered at the dose of 250
      mg/kg/day by gavage for 12 days. RESULTS: Obtained results revealed that
      administration of CCl4 caused a significant increase in plasma ASAT, ALAT, ALP
      and LDH activities and total bilirubin concentration, compared to the control
      group. While, albumin and total protein concentration were significantly lower.
      Additionally, a significant decrease in the level of hepatic GSH, GPx and GST
      activities associated with a significant increase of MDA content in CCl4 group
      than those of the control. However, the treatment of experimental rats with AEJP
      prevented these alterations and maintained the antioxidant status. The
      histopathological observations supported the biochemical evidences of
      hepatoprotection. CONCLUSIONS: The results of the present investigation indicate
      that J. Phoenicea possesses hepatoprotective activity and this effect was may be
      due to its antioxidant properties.

PMID- 28442110
TI  - Ethanolic extracts of babandotan leaves (Ageratum conyzoides L.) prevents
      inflammation and proteoglycan degradation by inhibiting TNF-alpha and MMP-9 on
      osteoarthritis rats induced by monosodium iodoacetate.
AB  - OBJECTIVE: To analyze the effects of Ageratum conyzoides L. on the monosodium
      iodoacetate induced osteoarthritis rats. METHODS: Thin layer chromatography was
      performed to analyze the constituents of the babandotan extract leaves. White
      male Sprague-Dawley rats used in this study were divided into 6 groups: normal
      control and negative control groups, both given 0.5% carboxymethyl cellulose; the
      positive control group that was given glucosamine and chondroitin suspension (486
      mg/200 g B.W.); the 3 dose variation extract groups including dose 1, 2, and 3
      that were given 40, 80, and 160 mg/200 g B.W. respectively on day 29 until 50.
      All the groups were induced with 0.05 mL monosodium iodoacetate (20 mg/mL) on day
      1, except normal control induced by saline. Measurement of edema volume of rat
      knees was performed on day 0, 8, 15, 22, 29, 43, and 50. Hematology data was
      measured at day 1, 29 and 50. Serum was collected at day 50 to evaluate TNF-alpha
      and MMP-9 by ELISA. Cartilage histopathology was evaluated by staining with H&E
      and Safranin-O-fast green staining on day 50. RESULTS: The babandotan leaves
      extract dose 2 (80 mg/200 g B.W.) and dose 3 (160 mg/200 g B.W.) could decrease
      the edema volume, increase the area and thickness of articular cartilage, and
      increase proteoglycan level. Particularly, dose 3 (160 mg/200 g B.W.) of extract
      babandotan leaves were able to significantly decrease the number of leukocytes,
      lymphocytes and udem volume, and decrease TNF alpha and MMP-9 levels.
      CONCLUSIONS: Babandotan leaves extract can recover inflammation and cartilages
      degradation by inhibiting TNF-alpha in inflammation processes and MMP-9 in the
      collagenase reaction in the cartilages.

PMID- 28442111
TI  - Toxicity assessment and screening of tetrodotoxin in the oblong blowfish
      (Takifugu oblongus) from the Tamil Nadu Coast of Bay of Bengal, India.
AB  - OBJECTIVE: To assess the toxicity of the pufferfish Takifugu oblongus, from
      Chennai coast, Tamil Nadu, India and to detect the presence of Tetrodotoxin
      (TTX). METHODS: The toxicity was evaluated by mouse bioassay using Swiss Albino
      mice which were expressed in mouse units (MU). Gross anatomical features were
      observed which is followed by histopathology of the dead mice tissues to
      establish the toxicity. Instrumental analysis for the presence of tetrodotoxin
      was also performed through GC-MS and HPLC. RESULTS: The toxicity of ovary was the
      maximum with 163 MU/g and lowest toxicity was observed in skin with 75.88 MU/g.
      Histopathological analyses of the dead mice showed various cellular degenerations
      and inflammations. The amount of Tetrodotoxin detected through GC-MS and HPLC was
      more reliable and sensitive than the customary mouse bioassay as instrumental
      analyses were able to detect even nanograms of the toxin. CONCLUSIONS: The
      present study evidently proved that Takifugu oblongus is highly toxic and
      consumption of the same can pose serious threat for health and possible lethality
      to humans.

PMID- 28442112
TI  - Experimental infection with Yersinia pseudotuberculosis in European brown hare
      (Lepus europaeus, Pallas).
AB  - OBJECTIVE: To investigate clinicopathological, bacteriological and pathological
      aspects of an experimental infection with Yersinia pseudotuberculosis (Y.
      pseudotuberculosis) in hares to verify the efficacy of serology for the in vivo
      diagnosis. Moreover, the pathogenicity of two Y. pseudotuberculosis strains was
      investigated in order to detect potential differences. METHODS: Twelve European
      brown hares (Lepus europaeus, Pallas) were experimentally infected per os and via
      conjunctival mucosae with Y. pseudotuberculosis: six subjects were infected with
      a strain isolated from a naturally infected hare (YpH) and six subjects with a
      strain isolated from a naturally infected rabbit (YpR). Two hares were used as
      negative controls. All animals were subjected to clinical, bacteriological and
      serological examinations during 9 weeks following the infection and, at the end
      of the control period, subjects still alive were euthanized and submitted to a
      complete post mortem examination. RESULTS: All faecal samples collected during
      the control period were positive for bacteriological examinations and to a PCR
      for the inv gene of Y. pseudotuberculosis, while only one YpH-infected hare
      showed a positive haemocultures. From the 2nd to the 9th week post infection
      (pi), serological analysis revealed specific antibodies with titers ranging from
      1:10 to 1:160 in all YpH-infected and two YpR-infected subjects. All the YpH
      infected and two YpR-infected hares scored positive for Y. pseudotuberculosis by
      means of bacteriological investigations. Grossly, suppurative multifocal lesions
      were detected in liver, spleen, kidney and sub-mandibular lymph nodes in both YpH
      and YpR-infected hares and confirmed with histopathology. Pulmonary lesions were
      observed only in YpH-infected subjects. Immunohistochemistry confirmed the
      presence of bacterial antigen in all infected animals. CONCLUSION: Results of
      this study revealed that YpH strain is more pathogenic for hares than the YpR
      strain; moreover the serological test performed in this study could be used for
      the diagnosis of pseudotuberculosis in hares, whereas post mortem diagnosis
      should be confirmed by means of bacteriological examination, PCR, histopathology
      and immunohistochemistry.

PMID- 28442113
TI  - Temporal patterns of dengue epidemics: The case of recent outbreaks in Kaohsiung.
AB  - OBJECTIVE: To investigate whether major dengue outbreaks in the last two decades
      in Kaohsiung follow a precise temporal pattern. METHODS: Government daily lab
      confirmed dengue case data from three major dengue outbreaks occurring during the
      last two decades in Kaohsiung in 2002, 2014 and 2015, is utilized to compute the
      corresponding weekly cumulative percentage of total case numbers. We divide each
      of the three time series data into two periods to examine the corresponding
      weekly cumulative percentages of case numbers for each period. Pearson's
      correlation coefficient was calculated to compare quantitatively the similarity
      between the temporal patterns of these three years. RESULTS: Three cutoff points
      produce the most interesting comparisons and the most different outcomes.
      Pearson's correlation coefficient indicates quantitative discrepancies in the
      similarity between temporal patterns of the three years when using different
      cutoff points. CONCLUSIONS: Temporal patterns in 2002 and 2014 are comparatively
      more similar in early stage. The 2015 outbreak started late in the year, but
      ended more like the outbreak in 2014, both with record-breaking number of cases.
      The retrospective analysis shows that the temporal dynamics of dengue outbreaks
      in Kaohsiung can strongly vary from one year to another, making it difficult to
      identify any common predictor.

PMID- 28442114
TI  - Nested multiplex PCR for identification and detection of human Plasmodium species
      including Plasmodium knowlesi.
AB  - OBJECTIVE: To develop a new technique for diagnosis of Plasmodium knowlesi and at
      the same time to be able to discriminate among the diverse species of Plasmodium
      causing human malaria. METHODS: In this study the nested multiplex malaria PCR
      was redesigned, targeting the 18S rRNA gene, to identify the fifth human
      Plasmodium species, Plasmodium knowlesi, together with the other human Plasmodium
      (Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium
      malariae) by amplified fragment size using only two amplification processes and
      including an internal reaction control to avoid false negatives. RESULTS: The
      technique was validated with 91 clinical samples obtained from patients with
      malaria compatible symptoms. The technique showed high sensitivity (100%) and
      specificity (96%) when it was compared to the reference method employed for
      malaria diagnosis in the Instituto de Salud Carlos III and a published real-time
      PCR malaria assay. CONCLUSIONS: The technique designed is an economical,
      sensitive and specific alternative to current diagnosis methods. Furthermore, the
      method might be tested in knowlesi-malaria endemic areas with a higher number of
      samples to confirm the quality of the method.

PMID- 28442115
TI  - Lipase inhibitory activity of Lagenaria siceraria fruit as a strategy to treat
      obesity.
AB  - OBJECTIVE: To explore pancreatic lipase inhibitory activity under different
      extraction conditions in order to track the most potent extract. METHODS: The
      methanolic extract and its fractions in solvents of increasing polarity, ether,
      chloroform, ethyl acetate, n-butanol and water, were made through cold
      maceration. Extracts in ethanol, ethyl acetate, acetone and chloroform were
      similarly prepared. Aqueous extract was prepared through hot decoction method. A
      reported method was used to determine lipase inhibitory activity of extracts and
      fractions over wide ranges of concentrations. RESULTS: The extracts and fractions
      exhibited concentration dependent activity. The IC50 (MUg/mL) values of
      methanolic, ethanolic, chloroform, ethyl acetate, acetone, ethyl acetate (after
      washing with water) and aqueous decoction were 293.40, 266.47, 157.59, 182.12,
      352.34, 257.00, and 190.00, respectively. The activity of chloroform, ethyl
      acetate and aqueous extracts were close to that of the drug orlistat (IC50 146
      MUg/mL). Out of the fractions of the methanolic extract, the chloroform fraction
      was most active (IC50 189.6 MUg/mL). The order of inhibitory activity of the
      fractions was as follows: chloroform>ether>n-butanolic>aqueous>ethyl acetate. The
      GC/MS analysis of the most active chloroform faction showed the presence of
      hexadecanoic acid, methyl hexadecanoate, isopropyl palmitate, methyl 9,12
      octadecadienate, and methyl 9,12,15-octadecatrienoate. CONCLUSIONS: The study
      suggests that Lagenaria siceraria has potential to inhibit pancreatic lipase
      activity, suppressing lipid digestion and thereby diminishing entry of lipids
      into the body. Regular intake of aqueous decoction of the fruit may therefore be
      recommended for control of obesity. Fatty acids and their esters may play role as
      inhibitors of lipase.

PMID- 28442116
TI  - Determination of delta-9-tetrahydrocannabinol content of cannabis seizures in
      Egypt.
AB  - OBJECTIVE: To determine the delta-9-tetrahydrocannabinol (THC) content of
      cannabis seizures in Egypt. METHODS: Unheated and heated extracts of cannabis
      seizures were prepared from the dried flowering tops and leaves (marijuana) or
      from the resin (hashish) and subjected to analysis using high performance liquid
      chromatography (HPLC). RESULTS: The heated resin extract had the peak of THC in a
      relative ratio of 31.34%, while extracting the resin directly without heating
      contained only 18.34% of THC. On the other hand, marijuana showed minimum
      percentage of THC at 11.188% on heating and 9.55% without heating. CONCLUSIONS:
      These results indicate the high potency of the abused cannabis plant in the
      illicit Egyptian market.

PMID- 28442117
TI  - Tuberculosis/toxoplasmosis co-infection in Egyptian patients: A reciprocal
      impact.
AB  - OBJECTIVE: To assess the concurrent toxoplasmosis infection in Egyptian TB
      patients and the impact of each infection on the other in terms of increased
      severity of TB or reactivation of latent Toxoplasma infection. METHODS: Three
      hundred suspected pulmonary TB cases were initially screened for TB using direct
      Ziehl Neelsen staining and Lowenstein Jensen culture of their sputa. Rifampicin
      resistance was detected by Xpert MTB/RIF assay. Control group of 30 age and sex
      matched healthy individuals negative for TB was included for comparison. All
      subjects were further assessed for serum levels of anti-Toxoplasma IgG antibodies
      and malondialdehyde (MDA). RESULTS: Forty three confirmed TB-infected patients
      including 10 (23.3%) rifampicin-resistant patients were detected. Associated
      toxoplasmosis was found to be significantly higher among TB patients (OR = 2.709;
      95% CI: 1.034-7.099; P<0.05) and among rifampicin sensitive than rifampicin
      resistant TB patients (OR=0.213; 95% CI: 0.048-0.951; P < 0.05). Serum levels of
      anti-Toxoplasma IgG antibodies and MDA were significantly higher among TB
      patients than the control group. Furthermore, serum level of MDA was
      significantly higher among TB/Toxoplasma co-infected patients as compared to
      toxoplasmosis free-TB patients. Strong positive correlation was detected between
      serum levels of anti-Toxoplasma IgG and MDA in TB patients (r = 0.75, P = 0.001).
      CONCLUSIONS: Among pulmonary TB Egyptian patients, there is a considerable
      prevalence of toxoplasmosis. Severity of pulmonary tuberculosis could be
      increased by Toxoplasma co-infection.

PMID- 28442118
TI  - Temperature and development of Zika virus infection: An Indonesian case.

PMID- 28442119
TI  - American Gastroenterological Association Institute Guideline on the Role of
      Elastography in the Evaluation of Liver Fibrosis.

PMID- 28442120
TI  - American Gastroenterological Association Institute Technical Review on the Role
      of Elastography in Chronic Liver Diseases.
AB  - Chronic liver diseases (CLDs), due to chronic hepatitis C; hepatitis B;
      nonalcoholic fatty liver diseases (NAFLD); and alcoholic liver disease, are a
      leading cause of morbidity and mortality globally. Early identification of
      patients with cirrhosis at high risk of progression to liver-related
      complications may facilitate timely care and improve outcomes. With risks and
      misclassification associated with invasive tests, such as liver biopsy,
      noninvasive imaging modalities for liver fibrosis assessment have gained
      popularity. Therefore, the American Gastroenterological Association prioritized
      clinical guidelines on the role of elastography in CLDs, focusing on vibration
      controlled transient elastography (VCTE) and magnetic resonance elastography
      (MRE). To inform these clinical guidelines, the current technical review was
      developed in accordance with the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) framework for diagnostic accuracy studies.
      This technical review addresses focused questions related to: (1) comparative
      diagnostic performance of VCTE and MRE relative to nonproprietary, serum-based
      fibrosis markers for detection of cirrhosis in patients with hepatitis C virus
      (HCV), hepatitis B virus (HBV), NAFLD, and alcoholic liver diseases; (2)
      performance of specific VCTE-defined liver stiffness cutoffs as a test
      replacement strategy (to replace liver biopsy) in making key decisions in the
      management of patients with CLDs; and (3) performance of specific VCTE-defined
      liver stiffness cutoffs as a triage test to identify patients with low likelihood
      of harboring high-risk esophageal varices (EVs) or having clinically significant
      portal hypertension (for presurgical risk stratification). This technical review
      does not address performance of other noninvasive modalities for assessing
      fibrosis (eg, acoustic radiation force pulse imaging or shear wave elastography)
      or steatosis (controlled attenuation parameter or magnetic resonance imaging
      estimated proton density fat fraction).

PMID- 28442121
TI  - Hepatitis C Virus Infection Care Pathway-A Report From the American
      Gastroenterological Association Institute HCV Care Pathway Work Group.

PMID- 28442122
TI  - The Effect of Temperature on Cyclic Fatigue of Nickel-titanium Rotary Endodontic
      Instruments.
AB  - INTRODUCTION: This study examined the effect of different temperatures on the
      cyclic fatigue of nickel-titanium rotary files. METHODS: Three groups of nickel
      titanium rotary files (EF group [EdgeFile; EdgeEndo, Albuquerque, NM], VB group
      [Vortex Blue; Dentsply Tulsa Dental Specialties, Tulsa, OK], and ESX group [ESX;
      Brasseler USA, Savannah, GA]) of size 25 with a .04 taper and 25-mm length were
      tested in a metal block that simulated a canal curvature of 60 degrees  and a 5
      mm radius curvature. The block was submerged in a water bath filled with water at
      3 degrees C, 22 degrees C, 37 degrees C, and 60 degrees C. At each temperature,
      30 files from each group were rotated at 500 rpm in the block. The number of
      cycles to fracture (NCF) was calculated. Statistical analysis was completed using
      a 1-way analysis of variance with significance at P < .05. RESULTS: VB group
      showed a significant decrease in NCF as the temperature increased from 3 degrees
      C to 60 degrees C. The ESX group showed a significant decrease in NCF as the
      temperature increased from 3 degrees C to 37 degrees C. The EF group showed a
      significant increase in NCF from 3 degrees C to 22 degrees C and a significant
      decrease in NCF from 22 degrees C to 37 degrees C. For each temperature, the EF
      group showed higher NCF than the VB group, which showed higher NCF than the ESX
      group. CONCLUSIONS: In this in vitro study, temperature was found to
      significantly affect the cyclic fatigue of nickel-titanium rotary files. At each
      tested temperature, NCF was the highest for the EF group followed by the VB group
      and lowest for the ESX group. Future cyclic fatigue studies should be conducted
      at body temperature.

PMID- 28442123
TI  - Corrigendum.

PMID- 28442124
TI  - Retracted.

PMID- 28442125
TI  - Relation of Risk Factors and Abdominal Aortic Calcium to Progression of Coronary
      Artery Calcium (from the Framingham Heart Study).
AB  - Coronary artery calcium (CAC) and abdominal aortic calcium (AAC) on multidetector
      computed tomography (MDCT) permit assessment of the presence and burden of
      coronary and systemic atherosclerosis. Risk factors for progression of CAC and
      AAC and the association of AAC with CAC progression have not been well
      characterized in a community-dwelling cohort. We studied 1,959 asymptomatic
      participants from the Framingham Heart Study who underwent serial MDCT scans with
      a median interval of 6.1 years. Primary outcomes were (a) the incidence of CAC
      and AAC (CAC >0 and AAC >0 with baseline CAC = 0 and AAC = 0) and (b) absolute
      progression of CAC (CAC > baseline CAC and AAC > baseline AAC). Covariates were
      collected at adjacent cycle examinations and included age, gender, use of
      antihypertensive therapy, use of lipid-lowering therapy, cigarette smoking, and
      total and high-density lipoprotein cholesterol. Predictors for CAC and AAC
      progression included baseline CAC, baseline AAC, lipid-lowering therapy,
      diabetes, high-density lipoprotein cholesterol, BMI, and serum creatinine.
      Multivariable stepwise logistic and linear regression models were used to test
      the association of these risk factors with CAC and AAC. Those who developed
      incident CAC on follow-up scanning comprised 18.8% of 1,124 participants, and
      84.9% of 780 participants, with detectable baseline CAC, had further progression.
      Baseline AAC was a predictor of both CAC incidence and progression, independent
      of other risk factors. In stepwise models, addition of baseline AAC slightly
      improved the area under the curve from 0.72 (0.68 to 0.76) to 0.74 (0.70 to
      0.78). In conclusion, standard cardiovascular disease risk factors are associated
      with incidence and progression of CAC and AAC, and AAC augments CAC incidence and
      progression above cardiovascular disease risk factors.

PMID- 28442126
TI  - Usefulness of Serial Measurements of Inferior Vena Cava Diameter by VscanTM to
      Identify Patients With Heart Failure at High Risk of Hospitalization.
AB  - Estimation of volume status is integral to heart failure (HF) management.
      Measurement of inferior vena cava (IVC) diameter (IVCd) by ultrasound provides a
      noninvasive estimate of right atrial pressures. The GE Vscan is a handheld
      ultrasound (HHU) device that allows for point-of-care measurements to assess
      volume status. We hypothesize that IVCd measurements using HHU can predict the
      risk of HF admission. We retrospectively analyzed a cohort of patients with HF
      treated in an ambulatory care setting over 17 months. Serial measurements of IVCd
      were obtained using HHU in the supine position from the subcostal window. Log
      binomial regression models were used to compare IVCd measurements between
      patients with and without HF admissions and to estimate the association between
      IVCd and risk of HF admission. Of the 355 patients with systolic (38%) and
      diastolic HF (62%) who were analyzed, 45% were women with a mean age of 73 years
      at the time of the first IVCd measurement. Overall, 3,488 measurements were
      obtained, and 32.4% of patients were hospitalized during follow-up. Patients with
      at least 1 hospital admission had a greater mean IVCd than those who were not
      admitted (2.0 vs 1.8 cm, p <0.01). In our analysis, every 0.5-cm increase in the
      mean IVCd was associated with a 38% increase in risk of HF admission (risk ratio
      [RR] 1.38, 95% CI 1.16 to 1.62, p <0.01). The risk of HF admission was also
      significantly increased in patients with IVCd 2.0 to 2.49 cm (RR 1.79, 95% CI
      1.27 to 2.52, p <0.01) and >=2.5 cm (RR 2.39, 95% CI 1.55 to 3.67, p <0.01),
      compared with patients with an IVCd < 2.0 cm. Increasing IVCd as measured by HHU
      at the point-of-care is associated with an increased risk of HF admission and may
      provide clinically useful information at the point-of-care to guide HF
      management.

PMID- 28442127
TI  - Precision Oncology: Are We There Yet?

PMID- 28442129
TI  - Injury risk and acute chronic workload ratio.

PMID- 28442128
TI  - Challenges in developing drugs for neurological and psychiatric disorders.

PMID- 28442130
TI  - Autoinflammatory Diseases in Pediatric Dermatology-Part 1: Urticaria-like
      Syndromes, Pustular Syndromes, and Mucocutaneous Ulceration Syndromes.
AB  - Monogenic autoinflammatory diseases are a heterogeneous emergent group of
      conditions that are currently under intensive study. We review the
      etiopathogenesis of these syndromes and their principal manifestations. Our aim
      is to propose a classification system based on the clinicopathologic features of
      typical skin lesions for routine clinical use in dermatology. Our focus is on
      diagnosis in pediatric practice given that this is the period when the signs and
      symptoms of these syndromes first appear. In Part 1 we discuss the course of
      urticaria-like syndromes, which include cryopyrin-associated periodic conditions
      and hereditary periodic fever syndromes. Pustular syndromes are also covered in
      this part. Finally, we review the range of therapies available as well as the
      genetic mutations associated with these autoinflammatory diseases.

PMID- 28442131
TI  - Multipoint recognition of domoic acid from seawater by dummy template molecularly
      imprinted solid-phase extraction coupled with high-performance liquid
      chromatography.
AB  - Due to the high cost of domoic acid (DA), different carboxylic acid compounds
      including indole-3-acetic acid (IAA), pyrrole-2-formic acid (PFA), pyridine-2,3
      dicarboxylic anhydride (PDA), trimesitinic acid (TA) and citric acid (CA) were
      investigated as dummy templates for the molecularly imprinted solid-phase
      extraction (MISPE) for selective isolation and pre-concentration of an amnesic
      shellfish poison (ASP), DA. The highest binding amount of the polymers towards DA
      was obtained when CA was used as dummy template owing to its high hydrophilicity.
      In addition, the "four-point" recognition site constructed by three COOH groups
      and a OH group in CA was also speculated to be the reason for the high binding
      amount of CA-MIPs and the rebinding of DA can be depend on the three COOH groups
      and a NH group with conformational change in the recognition process. Finally,
      the CA-MISPE column was chosen for DA isolation and pre-concentration and
      effective result was obtained with recoveries higher than 90% and relative
      standard deviation (RSD) less than 5% (n=3). This new polymer can be effectively
      applied to the monitoring and predicting the existence of trace DA.

PMID- 28442132
TI  - Gas chromatography with diode array detection in series with flame ionisation
      detection.
AB  - We introduce a gas chromatography detection approach that uses diode array
      detection operated in series with flame ionisation detection and demonstrate the
      utility of the detection approach for determination of volatile organic
      compounds. Diode array detection brings ultraviolet - visible spectroscopy (over
      a range of 190-640nm) onto the capillary gas chromatography time-scale, where
      average peak widths of analytes are on the order of 3-5s. The non-destructive
      nature of the diode array detector affords serially-coupled flame ionisation
      detection. This arrangement delivers near-simultaneous selective and universal
      detection without incurring additional analytical time, and without recourse to
      column flow splitting. The hyphenated technique is shown to be effective for
      chromatographic applications spanning an equivalent volatility range from C1 to
      C7n-paraffin hydrocarbons. The approach introduced herein provides increased
      sensitivity and selectivity for classes of compounds amenable to electronic
      spectroscopy such as alkenes, dienes, sulfurs, and aromatic compounds. The
      approach is demonstrated for direct measurement of carbon disulfide in work place
      atmospheres with a detection limit of 93pg on column and for the direct
      measurement of 1,3-butadiene in hydrocarbon matrices and ambient air with a
      detection of 73pg on column, each in less than 5min.

PMID- 28442133
TI  - Hybrid transgastric appendectomy is feasible but does not offer advantages
      compared with laparoscopic appendectomy: Results from the transgastric
      appendectomy study.
AB  - BACKGROUND: Very few transgastric procedures, the original objective of natural
      orifice translumenal surgery, have been reported in the international Natural
      Orifice Translumenal Surgery registers. In addition, most cases were controlled
      mainly by laparoscopy. To show the feasibility of hybrid transgastric
      appendectomy and to compare results with laparoscopic a prospective,
      nonrandomized study was conducted. METHODS: From October 2010 to May 2013,
      patients with acute appendicitis were screened. If the patients met the inclusion
      criteria, transgastric appendectomy was offered. If the patient decided on
      laparoscopy, the consenting patients took part in the observational part of the
      study. The transgastric appendectomy procedure was controlled completely by the
      gastroscope, although a 3 mm grasper was used to tauten the appendix. Demographic
      and clinical parameters were collected. Quality of life and pain were measured
      with a Short Form-8 questionnaire and the Visual Analogue Scale. RESULTS: Of the
      273 patients who underwent an appendectomy, 65 agreed to take part in this study.
      Out of these, 30 (46.15%) underwent transgastric appendectomy and 35 (53.85%)
      underwent laparoscopy. No intraoperative complications were recorded. The
      operation duration rate was greater in the transgastric appendectomy group (94.5
      minutes vs 69 minutes; P < .001). Conversions to open appendectomy and
      complications were the same. There were no differences in pain preoperatively or
      postoperatively. In both the transgastric appendectomy and laparoscopic groups,
      the quality of life of all the subscales increased markedly after successful
      resection of the pathology. CONCLUSION: These preliminary results demonstrate the
      feasibility of transgastric appendectomy. The postoperative course and quality of
      life are comparable with laparoscopic appendectomy, but no improvement due to
      transgastric appendectomy could be demonstrated.

PMID- 28442134
TI  - HPV vaccines - A review of the first decade.
AB  - Pre-adolescent girls (9-15years) have the option of receiving a two dose HPV
      vaccine series at either a six month or one year interval to provide protection
      from HPV 16, the most prevalent type associated with cervical cancers, as well as
      several other less prevalent types. This series of vaccinations is highly likely
      to protect her from HPV infection until she enters the routine screening program,
      whether that be primary HPV testing or a combination of HPV testing and cytology.
      The two dose program has been recommended by the World Health Organization (WHO)
      since 2015. For women 15years and older, the three dose vaccine schedule is still
      recommended. The past ten years of Gardasil use has provided evidence of reduced
      HPV 16/18 infections in countries where there has been high coverage. Gardasil9
      has replaced Gardasil. Gardasil9 has the same rapid anti-HPV 18 and HPV45 titer
      loss as Gardasil did. Cervarix remains equivalent to Gardasil9 in the prevention
      of HPV infections and precancers of any HPV type; Cervarix also has demonstrated
      sustained high antibody titers for at least 10years. One dose of Cervarix
      provides protection against HPV 16/18 infection with robust antibody titers well
      above natural infection titers. This may offer the easiest and most cost
      effective vaccination program over time, especially in low and lower middle
      income countries. Cervical cancer screening must continue to control cancer
      incidence over the upcoming decades. Future studies of prophylactic HPV vaccines,
      as defined by the WHO, must demonstrate protection against six month type
      specific persistent infections, not actual cervical cancer precursor disease
      endpoints, such as cervical intraepithelial neoplasia grade 3 (CIN 3) or
      adenocarcinoma in situ (AIS). This simplifies and makes less expensive future
      comparative studies between existing and new generic vaccines.

PMID- 28442135
TI  - [Anesthetic management of late pressure angioedema].
AB  - BACKGROUND AND OBJECTIVES: Late pressure angioedema is a rare form of angioedema
      in which light pressure stimulus can lead to edema after 1-12h. This uncommon and
      unreported entity is especially important in patients who undergo general
      anesthesia, for whom the usual harmless supine position, intravenous catheter
      insertion, standard monitoring, airway management and ventilation can lead to
      life threatening consequences as the trigger is a physical stimulus. CASE REPORT:
      In this report, we describe a successful perioperative anesthetic management of a
      30 year old patient, proposed for intra-ocular lens insertion, with a severe form
      of the disease with peri-oral, tongue and limb edema presentation. CONCLUSION:
      Due to lack of quality evidence, our conduct was based on the pathophysiology
      mechanisms of the syndrome, histamine and pro-inflammatory cytokines release,
      with special focus on a careful peri-operative assessment and prophylaxis,
      minimization of all the possible pressure stimulus, especially in the airway
      structures, and a strict post-operative monitoring.

PMID- 28442136
TI  - Re: Letter to the Editor in response to Kawada, 'The effect of smoking on the
      risk of primary open-angle glaucoma: an updated meta-analysis of six
      observational studies'.

PMID- 28442137
TI  - Enhanced surface ozone during the heat wave of 2013 in Yangtze River Delta
      region, China.
AB  - Under the background of global warming, occurrence of heat waves has increased in
      most part of Europe, Asia and Australia along with enhanced ozone level. In this
      paper, observational air temperature and surface ozone in the Yangtze River Delta
      (YRD) region of China during summer of 2013, and the regional chemistry-climate
      model (RegCM-CHEM4) were applied to explore the relationship between heat wave
      and elevated ground-level ozone. Observations indicated that YRD experienced
      severe heat waves with maximum temperature up to 41.1 degrees C, 6.1 degrees C
      higher than the definition of heat wave in China, and can last for as long as
      27days. Maximum ozone reached 160.5ppb, exceeding the national air quality
      standard (secondary level) as 74.7ppb. Moreover, ozone was found to increase at a
      rate of 4-5ppbK-1 within the temperature range of 28-38 degrees C, but decrease
      by a rate of -1.3~-1.7ppbK-1 under extremely high temperature. A typical heat
      wave case (HW: 24/7-31/7) and non-heat wave case (NHW: 5/6-12/6) were selected to
      investigate the mechanism between heavy ozone and heat waves. It was found that
      chemical reactions play the most important role in ozone formation during HW
      days, which result in 12ppb ozone enhancement compared to NHW days. Chemical
      formation of ozone can be influenced by several factors. During heat waves, a
      more stagnant condition, controlled by anti-cyclone with sink airflow, led to
      less water vapor in YRD from south and contributed to less cloud cover, which
      favored a strong solar radiation environment and ozone significantly increasing.
      High temperature also slightly promote the effect of vertical turbulence and
      horizontal advection, which beneficial to ozone remove, but the magnitude is much
      smaller than chemical effect. Our study suggests that the chemical reaction will
      potentially lead to substantial elevated ozone in a warmer climate, which should
      be taken into account in future ozone related issues.

PMID- 28442138
TI  - The role of personal values in children's costly sharing and non-costly giving.
AB  - This study examined whether children's values, global and abstract motivations
      serving as guiding principles, are organized similarly to those of adults,
      whether values can predict individual differences in children's sharing
      behaviors, and whether the normative nature of the situation influences the
      expression of these individual differences. Children (N=243, ages 5-12years)
      participated in a values ranking task as part of a visit to a science museum. The
      majority of children (n=150) also participated in a task examining costly sharing
      (i.e., sharing that results in giving up part of one's own resources) and non
      costly giving (i.e., giving that does not influence one's own share). Starting
      from 5years of age, children showed a structure of values similar to that of
      adolescents and adults, specifically contrasting preferences for opposing values
      (i.e., self-transcendence with self-enhancement and openness to change with
      conservation). Importance given to self-transcendence values related positively
      to costly sharing but not to non-costly giving, indicating that in situations
      where it is more normative to share, individual differences in values are less
      expressed in children's actual sharing. In addition, children's sex and age
      moderated the relation between values and behavior. Children's values are an
      important aspect of their developing personalities. Taking them into
      consideration can greatly promote the research of prosocial and normative
      development as well as our understanding of individual differences in children's
      behavior.

PMID- 28442139
TI  - Intraoperative ultrasound-assisted approach for endoscopic treatment of
      vesicoureteral reflux in children.
AB  - PURPOSE: Despite minimal invasiveness and high success rate, guidelines still
      prescribe voiding Cystourethrogram (VCUG) after endoscopic treatment for
      vesicoureteral reflux (VUR) in children. The aim of this paper was to analyze
      whether intraoperative ultrasound (IO-US) could improve surgical accuracy and
      perioperative counseling, thus potentially decreasing the need for postoperative
      VCUG. METHODS: We selected children treated for moderate to high grade VUR, renal
      scarring or repeated infections under antibiotic prophylaxis from January to
      December 2015. Endoscopic injection was combined with IO-US to detect optimal
      needle placement and to guide mound formation. IO-US findings were compared to
      surgeon opinion and postoperative VCUG, performed 3months after surgery. All
      patients were followed-up for 1year. RESULTS: A significant relationship was
      found between IO-US mound height (p=0.003) or localization (p<0.0005) and VCUG.
      Success of endoscopic treatment vs persistence of reflux groups had a mean mound
      height of 10.62+/-1.36mm and 8.39+/-1.08mm respectively (p<0.0005). Height
      maintained a significant correlation with success in simple and multivariable
      regression analysis. ROC curve determined >=9.8mm as predictor of reflux
      resolution (95% CI 0.825 to 0.998; p<0.0001). CONCLUSIONS: IO-US facilitates
      pediatric urologists to find an optimal location, to reach a volcano mound
      morphology and height, thus increasing intraoperative accuracy. IO-US also helps
      evaluating high-risk recurrence and guiding prognostic counseling. TYPE OF STUDY:
      Treatment study. LEVEL OF EVIDENCE: II.

PMID- 28442140
TI  - Cystic neutrophilic granulomatous mastitis associated with Corynebacterium
      including Corynebacterium kroppenstedtii.
AB  - Granulomatous (lobular) mastitis is a rare inflammatory breast disease affecting
      parous reproductive-aged women. Once considered idiopathic, there is growing
      evidence of an association with corynebacteria infection, especially in the
      setting of a distinct histological pattern termed cystic neutrophilic
      granulomatous mastitis (CNGM). We describe 15 cases with histological features
      either confirming (n = 12) or suggesting (n = 3) CNGM, and concurrent
      microbiological evidence of Corynebacterium species. The organism was detected by
      culture or 16S rRNA gene sequencing of specimens obtained at surgery or fine
      needle aspiration. In seven cases, Gram-positive organisms were seen within
      vacuolated spaces. Speciation was performed in nine cases, with Corynebacterium
      kroppenstedtii subsequently identified. These cases provide further evidence in
      support of this association and in doing so highlight the importance of
      recognising these histological clues as well as the limitations of Gram stain and
      microbiological culture in detecting this previously under-recognised disease
      process.

PMID- 28442141
TI  - Influence of patient rotational malpositioning on pelvic parameters assessed on
      lateral radiographs.
AB  - AIM: To estimate the effect of patients' axial rotation (AR) during pelvic
      radiograph acquisition, on the reliability and validity of sagittal pelvic
      parameters. MATERIALS AND METHODS: Lateral digitally reconstructed radiographs
      (LDRRs) were obtained from the pelvic computed tomography (CT) scans of eight
      children and nine adults. Then, the AR of the pelvis was simulated and the
      corresponding LDRRs were reconstructed at 5 degrees , 10 degrees , 15 degrees ,
      and 20 degrees  of the AR. Pelvic parameters were measured digitally on each
      radiograph. Intra- and interobserver variability were evaluated at each AR
      position (three operators repeated the measurements three times each). The bias
      on each clinical parameter, in each AR position, was calculated relatively to the
      0 degrees  position. RESULTS: Interobserver variability increased similarly in
      children and adults with AR. It reached 4.4 degrees  for pelvic incidence and 4.7
      degrees  for the sacral slope at 20 degrees  of AR. Biases on radiological
      parameters increased with AR and exceeded the acceptable threshold of errors when
      AR reached 10 degrees . A linear regression was established (R2=0.834, p<0.0001)
      in order to estimate the AR of a patient on a lateral pelvic radiograph based on
      the measurement of the bifemoral distance normalized to the sagittal pelvic
      thickness. CONCLUSIONS: AR of patients during radiograph acquisition can be
      estimated in clinical practice, which would allow physicians to discard any
      radiographs where the calculated AR exceeded 10 degrees .

PMID- 28442142
TI  - Predictors of therapeutic effect of transarterial chemoembolisation using drug
      eluting beads for hepatocellular carcinoma.
AB  - AIMS: To identify predictors of a therapeutic effect after transarterial
      chemoembolisation using drug-eluting beads (DEB-TACE) for hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Between January 2015 and July 2015,
      tumour variables and angiographic data were collected for 25 patients (49 target
      lesions) after they had undergone the DEB-TACE procedure for HCC. The therapeutic
      effect was evaluated according to the Response Evaluation Criteria in Cancer of
      the Liver at follow-up dynamic computed tomography (CT) performed within 1-4
      months after the procedure. A p<0.05 was considered significant. RESULTS: On a
      target lesion basis, the objective response (TE3/4) rate was 63.3% (31 of 49). On
      univariate analysis, larger size (>=2 cm) was a predictor of an objective
      response (p=0.029). The tumour location of the medial (segment 4) or caudate
      (segment 1) lobe also indicated a poor therapeutic effect (TE1/2), but not at the
      level of significance (p=0.051). Multivariate analysis identified tumour size
      (odds ratio, 8.60; 95% confidence interval, 1.87-62.8) and tumour location (odds
      ratio, 12.2; 95% confidence interval, 2.12-129.8) as significant factors
      associated with a therapeutic effect. On a patient basis, 10 of 25 (40%) patients
      showed complete response/partial response. There were no significant differences
      between complete response/partial response and stable disease/progressive disease
      regarding age, gender, tumour markers, history of previous treatment, Child-Pugh
      class, T-stage, or Barcelona Clinic Liver Cancer Staging. CONCLUSION: A short
      term therapeutic effect was associated with tumour size and location on a target
      lesion basis.

PMID- 28442143
TI  - Polypropylene mesh seeded with fibroblasts: A new approach for the repair of
      abdominal wall defects in rats.
AB  - PURPOSE: The purpose of study was to develop bioengineered scaffolds by seeding
      primary mouse embryo fibroblast cells (p-MEF) on polypropylene mesh and to test
      its efficacy for the repair of abdominal wall defects in rats. METHODS: The study
      was conducted on 18 clinically healthy adult Wistar rats of either sex. The
      animals were randomly divided into two equal groups having nine animals in each
      group. In both the groups a 20mm*20mm size full thickness muscle defect was
      created under xylazine and ketamine anesthesia in the mid-ventral abdominal wall.
      In group I the defect was repaired with polypropylene mesh alone and in group II
      it was repaired with p-MEF seeded polypropylene mesh. Matrices were implanted by
      synthetic absorbable suture material (polyglycolic acid) in continuous suture
      pattern. The efficacy of the bio-engineered matrices in the reconstruction of
      full thickness abdominal wall defects was evaluated on the basis of macro and
      histopathological observations. RESULTS: Macroscopic observations revealed that
      adhesions with skin and abdominal viscera were minimum in group II as compared to
      group I. Histopathological observations confirmed better fibroplasia and collagen
      fiber arrangement in group II. No recurrence of hernia was found in both the
      groups. CONCLUSION: Hernias are effectively repaired by implanting polypropylene
      mesh. However, this work demonstrates that in vitro seeding of mesh with
      fibroblasts resulted in earlier subsidization of pain, angiogenesis and
      deposition of collagen, increased thickness of matrices with lesser adhesions
      with underlying viscera. On the basis of the results p-MEF seeded mesh was better
      than non-seeded mesh for repair of abdominal wall defects in rats.

PMID- 28442144
TI  - A proposal to evaluate the fibers' break probability in ligaments and tendons.
AB  - Understanding the yield and failure mechanisms of ligaments and tendons is
      important to have a deeper knowledge of their structure and function. Evaluating
      what are the limits of the human body is also important to prevent injuries in
      workers, in athletes and the elderly. The tissue yield mechanism was analyzed by
      modifying and extending a probabilistic model of collagen bundles. Since not
      usable experimental data are available in the literature, the model and the
      method were tested using Monte Carlo simulations. The simulations showed many
      crucial aspects of the model and gave some indications about possible future real
      validation experiments. The analysis of the correlation between the simulated
      data, the model (R2) and the Signal-to-Noise-Ratio (SNR) highlighted the most
      important parameters that affect effectiveness of the described method: number of
      fibers, elongation step, noise. This analysis also showed that the numerical
      differentiation algorithms of the data have a key role on the accuracy of the
      yield assessment. However, the results also showed that the method is able to
      correctly estimate the elongation break distribution of the fibers of ligaments
      and tendons.

PMID- 28442145
TI  - Mechanical characteristic and biological behaviour of implanted and restorative
      bioglasses used in medicine and dentistry: A systematic review.
AB  - OBJECTIVE: Nowadays bioactive glasses are finding increasing applications in
      medical practice due to their ability to stimulate re-mineralisation. However,
      they are intrinsically brittle materials and the study of new compositions will
      open up new scenarios enhancing their mechanical properties and maintaining the
      high bioactivity for a broader range of applications. This systematic review aims
      to identify the relationship between the composition of bioactive glasses used in
      medical applications and their influence on the mechanical and biological
      properties. METHODS: Various electronic databases (PubMed, Science Direct) were
      used for collecting articles on this subject. This research includes papers from
      January 2011 to March 2016. PRISMA guidelines for systematic review and meta
      analysis have been used. 109 abstracts were collected and screened, 68 articles
      were read as relevant articles and a total of 22 papers were finally selected for
      this study. RESULTS: Most of the studies obtained enhanced mechanical properties
      and the conservation of bioactivity behaviours; although a lack of homogeneity in
      the characterization methods makes it difficult to compare data. SIGNIFICANCE:
      New compositions of bioactive glasses incorporating specific ions and the
      addition in polymers will be the most important direction for future researches
      in developing new materials for medical applications and especially for
      dentistry.

PMID- 28442146
TI  - Research letter: Evaluating the future pathological N descriptors for lung cancer
      staging in a UK population.

PMID- 28442148
TI  - The more things change.

PMID- 28442147
TI  - Troubleshooter in electrical storm: Mechanical unloading leads to heart rhythm
      stabilization.
AB  - The electrical storm is a life-threatening situation which causes a complex
      antiarrhythmic treatment. We firstly report a rhythmological stabilization
      through mechanical unloading of the left ventricle in a health patient who
      developed electrical storm after endo- and epicardiac re-ablation and who
      previously underwent 27 unsuccessful defibrillations. No evidence for a specific
      etiology of the rhythm disturbances was found. After implantation of a
      percutaneous left ventricular assist device (pLVAD) a single additional
      defibrillation was needed to terminate ventricular fibrillation. This unique
      application of pLVAD might be an unprecedented escape strategy for patients who
      have exhausted all other commonly recommended therapy options.

PMID- 28442149
TI  - Bilateral pneumonectomies to treat uncontrolled sepsis in a patient awaiting a
      lung transplant.

PMID- 28442150
TI  - Porcine small intestine submucosa cylinder valve for mitral and tricuspid valve
      replacement.

PMID- 28442151
TI  - Up around the bend.

PMID- 28442152
TI  - Get it right the first time.

PMID- 28442153
TI  - Reducing stroke during cardiac surgery: Back flushing and manipulation is for
      plumbers, not surgeons.

PMID- 28442154
TI  - Pathogenesis and Treatment of Sole Ulcers and White Line Disease.
AB  - Sole ulcers and white line disease are 2 of the most common claw horn lesions in
      confined dairy cattle. Predisposing causes include unbalanced weight bearing, and
      metabolic, enzymatic, and hormonal changes. The white line serves as the junction
      between the sole and axial and abaxial wall. It is vulnerable to trauma and
      separation, permitting organic matter to become entrapped. Colonization
      contributes to retrograde movement of the infection to the solar and perioplic
      corium, where an abscess forms resulting in pain and lameness. Successful
      treatment requires an orthopedic foot block to the healthy claw and corrective
      trimming of the lesion.

PMID- 28442155
TI  - A rapid review of consumer health information needs and preferences.
AB  - OBJECTIVE: This rapid review summarizes best available evidence on consumers'
      needs and preferences for information about healthcare, with a focus on the
      Australian context. Three questions are addressed: 1) Where do consumers find and
      what platform do they use to access information about healthcare? 2) How do
      consumers use the healthcare information that they find? 3) About which topics or
      subjects do consumers need healthcare information? METHODS: A hierarchical
      approach was adopted with evidence first sought from reviews then high quality
      studies using Medline (via PubMed), CINAHL, Embase, the JBI Database of
      Systematic Reviews and Implementation Reports, the Campbell Collaboration Library
      of Systematic Reviews, EPPI-Centre, and Epistemonikos. RESULTS: Twenty-eight
      articles were included; four systematic reviews, three literature reviews,
      thirteen quantitative studies, six qualitative studies, and two mixed methods
      studies. CONCLUSION: Consumers seek health information at varying times along the
      healthcare journey and through various modes of delivery. Complacency with
      historical health information modes is no longer appropriate and flexibility is
      essential to suit growing consumer demands. PRACTICE IMPLICATIONS: Health
      information should be readily available in different formats and not exclusive to
      any single medium.

PMID- 28442156
TI  - Treatment decision-making in ductal carcinoma in situ: A mixed methods systematic
      review of women's experiences and information needs.
AB  - OBJECTIVE: Decision-making in ductal carcinoma in situ (DCIS) is complex due to
      the heterogeneity of the disease. This study aimed to understand women's
      experience of making treatment decisions for DCIS, their information and support
      needs, and factors that influenced decisions. METHODS: We searched six electronic
      databases, conference proceedings, and key authors. Two reviewers independently
      applied inclusion and quality criteria, and extracted findings. Thematic analysis
      was used to combine and summarise findings. RESULTS: We identified six themes and
      28 subthemes from 18 studies. Women with DCIS have knowledge deficits about DCIS,
      experience anxiety related to information given at diagnosis and the complexity
      of decision-making, and have misconceptions regarding risks and outcomes of
      treatment. Women's decisions are influenced by their understanding of risk, the
      clinical features of their DCIS, and the benefits and harms of treatment options.
      Women are dissatisfied with the decisional support available. CONCLUSIONS:
      Informed and shared decision-making in this complex decision setting requires
      clear communication of information specific to DCIS and individual's, as well as
      decision support for patients and clinicians. PRACTICE IMPLICATIONS: This
      approach would educate patients and clinicians, and assist clinicians in
      supporting patients to an evidence-based treatment plan that aligns with
      individual values and pReferences.

PMID- 28442157
TI  - Gilliamella intestini sp. nov., Gilliamella bombicola sp. nov., Gilliamella bombi
      sp. nov. and Gilliamella mensalis sp. nov.: Four novel Gilliamella species
      isolated from the bumblebee gut.
AB  - Spectra of five isolates (LMG 28358T, LMG 29879T, LMG 29880T, LMG 28359T and R
      53705) obtained from gut samples of wild bumblebees of Bombus pascuorum, Bombus
      lapidarius and Bombus terrestris were grouped into four MALDI-TOF MS clusters.
      RAPD analysis revealed an identical DNA fingerprint for LMG 28359T and R-53705
      which also grouped in the same MALDI-TOF MS cluster, while different DNA
      fingerprints were obtained for the other isolates. Comparative 16S rRNA gene
      sequence analysis of the four different strains identified Gilliamella apicola
      NCIMB 14804T as nearest neighbour species. Average nucleotide identity values of
      draft genome sequences of the four isolates and of G. apicola NCIMB 14804T were
      below the 96% threshold value for species delineation and all four strains and G.
      apicola NCIMB 14804T were phenotypically distinct. Together, the draft genome
      sequences and phylogenetic and phenotypic data indicate that the four strains
      represent four novel Gilliamella species for which we propose the names
      Gilliamella intestini sp. nov., with LMG 28358T as the type strain, Gilliamella
      bombicola sp. nov., with LMG 28359T as the type strain, Gilliamella bombi sp.
      nov., with LMG 29879T as the type strain and Gilliamella mensalis sp. nov., with
      LMG 29880T as the type strain.

PMID- 28442158
TI  - Diversity and evolutionary aspects of mucin binding (MucBP) domain repeats among
      Lactobacillus plantarum group strains through comparative genetic analysis.
AB  - Mucin binding protein (Mub) of Lactobacillus plantarum- group (LPG) is considered
      as a potential marker gene due to its diversity and adherence property to host
      intestinal layer. We recently observed strain specific diversity in mub gene of
      LPG strains (n=8) and grouped them into Type I, II and III based on the insertion
      and/or deletion of MucBP domain repeats (Devi et al., 2016). The mub gene
      expression pattern noted by real-time PCR revealed 67.64 increased fold change in
      MTCC 9483 with four MucBP repeats. Whereas, the isolates with 3 and 2 MucBP
      repeats showed ~4 and 2 enhanced expression, respectively. Detection of integrase
      (int) and transposases (tra) in the flanking regions of mub, suggested variation
      in amplicon sizes and revealed strain diversity. The IS finder program identified
      tra nucleotide sequence similarity towards IS256 and IS5 family insertion
      elements that are present among other lactic acid bacteria. Phylogenetic
      dendrogram suggested the evolution of D7-D10 domains of L. paraplantarum MTCC
      9483 from Lactobacillus namurensis, Lactobacillus hammesii and Lactobacillus
      spicheri. These results collectively gave information on the genetic diversity,
      functional MucBP domains and also facilitated in the selection of an efficient
      novel LPG strain with good adherence ability.

PMID- 28442159
TI  - Cochrane Corner: Antihypertensive efficacy of beta-1 selective beta blockers for
      primary hypertension.
AB  - Beta blockers are commonly used to treat hypertension. This Cochrane systematic
      review assessed the effect of beta-1 selective beta blockers on blood pressure
      (BP), pulse pressure (PP), heart rate (HR) and withdrawal due to adverse effects
      in patients with primary hypertension. Fifty-six randomized placebo-controlled
      trials were included, with a total of 7812 patients. These drugs reduced
      systolic/diastolic BP by 10/8 mmHg, PP by 2 mmHg and HR by 11 bpm; no difference
      was found between treatment and placebo regarding withdrawal due to adverse
      effects. Differences in efficacy were observed between the various beta-1
      selective beta blockers, which may be due to methodological differences in the
      trials. The choice of an antihypertensive drug should take into account not only
      its efficacy in reducing BP but also its tolerability, its efficacy in preventing
      cardiovascular events, and other factors such as undesirable metabolic effects.

PMID- 28442160
TI  - Multiple lumens in a left anterior descending coronary artery.

PMID- 28442161
TI  - Zurich Cementless Total Hip Replacement.
AB  - Total hip replacement (THR) is the gold standard treatment of intractable pain
      from hip dysplasia. THR procedures are divided into 2 main categories: cemented
      and cementless, with hybrid a combination. The Zurich Cementless THR system uses
      a combination of press-fit (acetabular component) and locking screw (femoral
      component) fixation designed to address the main challenge facing cemented
      systems (aseptic loosening) while providing the benefit of immediate stability
      with its novel locking screw implantation system for the femoral stem. The Zurich
      THR system is an effective treatment option for orthopedic conditions of the
      coxofemoral joint in medium to giant breed dogs.

PMID- 28442162
TI  - Morbidity of Metastasectomy for Renal Cell Carcinoma: Emerging Evidence and Unmet
      Needs.

PMID- 28442163
TI  - The Search for the Missing Heritability of Prostate Cancer.
AB  - Scientists and clinicians at Johns Hopkins have been working since 1987 to
      uncover the genetic pathogenesis of prostate cancer. A patient query about the
      hereditary nature of the disease led to data collection on family history,
      followed by segregation and linkage analyses. Collaborative investigations using
      next-generation sequencing to identify genetic variants associated with prostate
      cancer risk have revealed the significance of HOXB13, BRCA 1/2, and DNA repair
      mutations.

PMID- 28442164
TI  - If You Want to Make an Important Discovery, Listen to Your Patients.
AB  - No one knows more about certain aspects of a disease than the patient who has it.
      So, listen to your patients and they may lead you in a direction in which no one
      else is going.

PMID- 28442165
TI  - Technical tips to enhance micrografting results in burn surgery.
AB  - The lack of autograft donor site is one of the greatest limiting factors for the
      treatment of extensive burn. Micrografting is an important revolution in burn
      surgery where autografts are cut into small pieces for wide and rapid coverage of
      burn wound. Our early experiences with the current standard micrografting
      technique were fraught with poor graft take as well being time and labor
      intensive. We have improvised our technique, where we combined the use of
      allograft to serve as a carrier for the micrograft. The objective of this paper
      is to share our experience in micrografting and several technical tips which had
      enhanced our micrografting results. The improvisation in our technique includes:
      (1) Single-stage 'micrograft-allograft sandwich method' where allograft served as
      a direct carrier for the micrografts. Micrografts were laid uniformly 1cm apart
      onto allograft sheets, creating a 1:9 expansion ratio. This technique replaced
      the original two stage method. (2) The use of the Meek device (Humeca,
      Netherlands) to prepare micrograft. The Meek device can rapidly produce 3mm
      micrografts for easy transfer with a fine forceps. (3) The use of slow-acting
      fibrin sealant to promote graft take and hemostasis. (4) A two-team approach for
      micrograft preparation where one team processes micrograft and another prepares
      the allograft sheets. This reduces the lag time between micrograft preparation
      and grafting, and reduces the overall surgery time. Micrografting remains an
      important treatment for major burn surgery. The aim of micro-allograft
      combination is to allow autografts re-epithelization under a reliable temporary
      skin coverage in a single stage procedure. A prospective study is warranted to
      measure the objective outcome of this renewed technique.

PMID- 28442166
TI  - Use of intraoperative index finger pulse oximetery during radial forearm flap
      harvest to prevent finger ischemia for reconstruction of hand burn and crush
      injuries.

PMID- 28442167
TI  - Tipping Points and Endogenous Determinants of Nigrostriatal Degeneration by MPTP.
AB  - The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a
      Parkinson's disease (PD)-like syndrome by inducing degeneration of nigrostriatal
      dopaminergic neurons. Studies of the MPTP model have revealed the pathomechanisms
      underlying dopaminergic neurodegeneration and facilitated the development of drug
      treatments for PD. In this review, we provide an update on MPTP bioactivation and
      biodistribution, reconcile the distinct views on energetic failure versus
      reactive oxygen species (ROS) formation as main drivers of MPTP-induced
      neurodegeneration, and describe recently identified intrinsic features of the
      nigrostriatal system that make it particularly vulnerable to MPTP. We discuss
      these new perspectives on the endogenous tipping points of tissue homeostasis and
      the drivers responsible for vicious cycles in relation to their relevance for the
      development of novel intervention strategies for PD.

PMID- 28442168
TI  - The evaluation of pattern and quality of sleep in patients with chronic
      rhinosinusitis with nasal polyps.
AB  - OBJECTIVE: The goal of this study is to evaluate the impact of chronic
      rhinosinusitis with nasal polyps (CRSwNP) on sleep pattern and sleep quality
      before and after functional endoscopic sinus surgery using subjective and
      objective parameters. METHODS: Twenty-two patients with CRSwNP were evaluated.
      All subjects underwent assessment by nasal endoscopy, rhinomanometry and computed
      tomography. Sleep pattern and sleep quality were evaluated by Pittsburgh sleep
      quality index (PSQI) and polysomnography (PSG). All patients were reassessed 6
      months after surgery. RESULTS: Nasal resistance decreased after the surgery
      (p<0.001). Postoperative PSQI scores were significantly lower than preoperative
      scores (p<0.001). The preoperative mean values of total apnea index and apnea
      hypopnea index were 25.4 and 13.3, respectively. After surgery, the total apnea
      and apnea-hypopnea index had decreased significantly to 7.8 and 11.2,
      respectively (p=0.009 and 0.019, respectively). CONCLUSION: In patients with
      CRSwNP, functional endoscopic sinus surgery significantly ameliorates sleep
      pattern and sleep quality. CRSwNP may be a predisposing factor for sleep related
      respiratory disorders.

PMID- 28442169
TI  - Cochlear implantation in children with anomalous cochleovestibular anatomy.
AB  - OBJECTIVE: The aim of the study is to assess the audiological and surgical
      outcome after cochlear implantation in children with inner ear malformation and
      to compare them with a group of congenitally deaf children implantees without
      inner ear malformation. INTRODUCTION: Children with profound sensorineural
      deafness with malformations of the inner ear represent a challenge, accounting to
      5-15% of congenital sensorineural deafness. These cases were originally regarded
      as a contraindication for cochlear implant surgery. METHODS: Retrospective study
      of 26 patients with congenital inner ear malformation, from a total population of
      329 cochlear implant patients. Radiological evaluation with high resolution
      computed tomography and magnet resonance was performed to all patients in order
      to evaluate all the preoperative conditions. All patients were tested using
      European Portuguese word discrimination tests (monosyllabic test, number test and
      sentences test), capacity of auditory performance (CAP) and speech
      intelligibility rating (SIR). RESULTS: In all 7.9% of deaf children in our center
      study have inner ear abnormalities. All children underwent successful
      implantation. CAP yielded an average 7.1 (+/-1.7), SIR 4.3 (+/-1.0). The children
      without inner ear abnormalities did not achieve statistically significant better
      scores. Two children had a perilymph gusher, and there were no other
      complications. CONCLUSION: Cochlear implantation can be successfully performed in
      children with inner ear malformation. Audiological performance after cochlear
      implantation in malformed inner ears is comparable to that found in other
      congenitally deaf patients. The risk of CSF leak is associated with inner ear
      abnormalities and should be anticipated during surgery.

PMID- 28442170
TI  - Platinum, palladium, gold and ruthenium complexes as anticancer agents: Current
      clinical uses, cytotoxicity studies and future perspectives.
AB  - Metallodrugs offer potential for unique mechanism of drug action based on the
      choice of the metal, its oxidation state, the types and number of coordinated
      ligands and the coordination geometry. This review illustrates notable recent
      progress in the field of medicinal bioinorganic chemistry as many new approaches
      to the design of innovative metal-based anticancer drugs are emerging. Current
      research addressing the problems associated with platinum drugs has focused on
      other metal-based therapeutics that have different modes of action and on prodrug
      and targeting strategies in an effort to diminish the side-effects of cisplatin
      chemotherapy. Examples of metal compounds and chelating agents currently in
      clinical use, clinical trials or preclinical development are highlighted.

PMID- 28442171
TI  - What are the real effects of the Mediterranean diet on recurrent colds and their
      complications?

PMID- 28442172
TI  - High-flow nasal cannula oxygenation for everyone? Not so fast!

PMID- 28442173
TI  - Analysis of tar compounds and quantification of naphthalene from thermal
      treatment of household biowaste.
AB  - Household biowaste represent the organic fraction of municipal solid waste and
      are an underutilized resource. Although previous studies have performed pyrolysis
      of organic waste, the vast majority has been on specific presorted feedstock or
      conventional lignocellulosic streams. Therefore, there is a lack of pyrolysis
      applications on representative food waste as retrieved from households and this
      can be attributed primarily to their high water content and their degradability.
      But via the intermediate step of drying, long-term storage and thermal treatment
      have become possible. In the framework of this study, household biowaste were
      pyrolyzed for the production of carbonaceous materials with a main focus on the
      analysis of produced tar compounds. Tars can be corrosive or cause clogging and
      disrupt the operation of pyrolysis and gasification plants. Their analysis has
      faced several difficulties due to inconsistency in the methodologies that have
      been applied by various groups. The tar protocol has provided a solid framework
      for consistent analysis of tars but until now has been solely used for the case
      of gasification. This study aimed to apply the tar protocol for pyrolysis and to
      enhance the detectability of the method for a wider range of tars by means of
      elemental analysis, attenuated total reflectance (ATR) and gas chromatography
      mass spectrometry (GC-MS). GC- MS was performed by means of a specific column for
      PAHs identification and calibration methods were developed for the proper
      quantification of naphthalene which is the dominant tar compound. The results of
      the analysis showed that naphthalene concentration increased from torrefaction to
      carbonization but then decreased significantly for high temperature pyrolysis at
      860  degrees C.

PMID- 28442174
TI  - Microstructural alterations owing to handling of bovine pericardium to
      manufacture bioprosthetic heart valves: A potential risk for cusp dehiscence.
AB  - INTRODUCTION: Cross-linking and anti-calcification of prosthetic heart valves
      have been continuously improved to prevent degeneration and calcification.
      However, non-calcific structural deteriorations such as cuspal dehiscences along
      the stent still require further analysis. MATERIAL AND METHOD: Based upon the
      previous analysis of an explanted valve after 7 years, a fresh commercial aortic
      valve was embedded in poly(methyl methacrylate) (PMMA) and cut into slices to
      ensure the detailed observation of the assembly and material structures. A
      pericardial patch embossed to provide the adequate shape of the cusps was
      investigated after paraffin embedding and appropriate staining. The
      microstructural damages that occurred during manufacturing process were
      identified and evaluated by light microscopy, polarized microscopy, scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS:
      The wavy collagen bundles, the key structure of the pericardium patch, were
      damaged to a great extent at suture sites along the stent and in the compressed
      areas around the stent post. The fixation of the embossed pericardium patch along
      the plots of the stent aggravated the microstructural modifications. The damages
      mainly appeared as the elimination of collagen bundle waviness and delamination
      between the bundles. CONCLUSION: Considering the modes of failure of the explant,
      the damages to the collagen bundles may identify the vulnerable sites that play
      an important role in the cusp dehiscence of heart valve implants. Such
      information is important to the manufacturers. Recommendations to prevent in vivo
      cusp dehiscence can therefore be formulated.

PMID- 28442175
TI  - Reframing continence care in care-dependence.
AB  - International guidelines promote active investigation and treatment of
      incontinence; however, these guidelines do not fully accommodate the psychosocial
      aspects associated with providing continence care i.e. the caregiving dynamics.
      The author developed a new framework that aims to support nurses and care workers
      in their efforts to identify and meet the continence care needs of individuals
      with complex health conditions who are dependent on another person for assistance
      to manage incontinence or to maintain continence. The framework is underpinned by
      two core concepts: 'dignity' and 'care', and is characterized by a focus on:
      empathic continence care; personhood in dementia; therapeutic communication;
      authentic partnership in continence care; acknowledging stigma, social taboos and
      courtesy stigma; and the need for a foundational continence assessment. This
      paper describes the Dignity in Continence Care Framework and suggests strategies
      for its use in the future education of nurses and care workers about continence
      care.

PMID- 28442176
TI  - Mastitis outcomes on pre-ovulatory follicle diameter, estradiol concentrations,
      subsequent luteal profiles and conception rate in Buffaloes.
AB  - The objectives of this study was to investigate the outcome of mastitis, in its
      clinical or subclinical forms, on the mean diameter of pre-ovulatory follicle
      (POF), plasma estradiol concentration on the day of estrus, subsequent luteal
      profile and subsequent conception rate in buffaloes. Sixty dairy buffalo (Bubalus
      bubalus) conducted in this study were divided into three groups {healthy (H),
      n=20; subclinical mastitis (SCM), n=18; and clinical mastitis (CM), n=22}.
      Ultrasonography of ovaries revealed that mean diameter of POF was larger (P<0.05)
      in H buffalo (14.35mm) compared to SCM (12.40mm) and CM (10.25mm). Also, plasma
      estradiol concentration on the day of estrus was higher (P<0.05) in H buffalo
      compared to SCM and CM counterparts; 34.95 vs. 32.87 and 27.50pg/ml,
      respectively. Besides, positive correlation was observed between the POF diameter
      with plasma estradiol concentration in H, SCM and CM buffaloes (r=0.64, 0.74,
      0.72 respectively, P<0.05). Moreover, positive correlations (P<0.01) were found
      on days 9, 12, 16, and 21 post-ovulation between POF diameter and luteal profile.
      Thus, the conception rate in H buffalo was higher (P<0.05) compared with SCM and
      CM counterparts; 55% vs. 38.89 and 18.18%, respectively. In conclusion, mastitis
      in its clinical or subclinical forms disrupts the functioning of the pre
      ovulatory follicle on the day of estrus, associated with low follicular estradiol
      production, resulting in suppression to subsequent luteal profile leading to
      substantial decrease in pregnancy consequence of buffaloes.

PMID- 28442177
TI  - Spinal manipulation is beneficial for nonchronic low back pain.

PMID- 28442178
TI  - Cardiopulmonary resuscitation in infant.

PMID- 28442179
TI  - Ipsilateral sagittal split ramus osteotomy to facilitate reconstruction of the
      temporomandibular joint after resection of condylar osteochondroma.
AB  - We report the outcomes of 12 patients with osteochondroma of the mandibular
      condyle who were treated by condylectomy with sagittal split ramus osteotomy
      (SSRO) between January 2011 and October 2015. Variables assessed before and after
      operation were imaging, appearance, maximum mouth opening, maximum mandibular
      protrusion, lateral excursion, and function of the temporomandibular joint (TMJ).
      Patients were followed up for a mean (range) of 21 (13 - 30) months. Outcomes
      were satisfactory with no complications or recurrence. Patients regained good
      occlusion and facial symmetry, and satisfactory function of the TMJ. Our results
      suggest that SSRO is a good option for condylar reconstruction after resection of
      mandibular condylar osteochondroma.

PMID- 28442180
TI  - Point-of-care ultrasound for oral and maxillofacial surgeons.
AB  - Point-of-care ultrasound is an ultrasound examination that is made at the bedside
      by the examining clinician in the Accident and Emergency department, clinic,
      ward, or operating theatre, and it has been growing in popularity since it was
      first introduced in the 1990s. It is used as an adjunct to clinical examination
      to aid diagnosis or treatment. We have carried out a pilot survey to assess
      whether oral and maxillofacial surgeons in the United Kingdom either need or
      desire to make such an examination. We present the results of our survey and
      discuss the uses and benefits of point-of-care ultrasound in oral and
      maxillofacial surgery.

PMID- 28442181
TI  - Hospitalizations for mitochondrial disease across the lifespan in the U.S.
AB  - IMPORTANCE: Mitochondrial disease is being diagnosed with increasing frequency.
      Although children with mitochondrial disease often have severe, life-limiting
      illnesses, many survive into adulthood. There is, however, limited information
      about the impact of mitochondrial disease on healthcare utilization in the U.S.
      across the lifespan. OBJECTIVES: To describe the characteristics of inpatient
      hospitalizations related to mitochondrial disease in the U.S., to identify
      patient-level clinical factors associated with in-hospital mortality, and to
      estimate the burden of hospitalizations on individual patients. DESIGN: Cross
      sectional and longitudinal observational studies. SETTING: U.S. hospitals.
      PARTICIPANTS: Individuals with hospital discharges included in the triennial
      Healthcare Cost and Utilization Project (HCUP) Kids Inpatient Database (KID) and
      the National Inpatient Sample (NIS) in 2012 (cross-sectional analysis);
      individuals with hospital discharges included in the HCUP California State
      Inpatient Database from 2007 to 2011, inclusive (longitudinal analysis).
      EXPOSURE: Hospital discharge associated with a diagnosis of mitochondrial
      disease. MAIN OUTCOME MEASURES: Total number and rate of hospitalizations for
      individuals with mitochondrial disease (International Classification of Diseases,
      9th revision, Clinical Modification code 277.87, disorder of mitochondrial
      metabolism); in-hospital mortality. RESULTS: In the 2012, there were
      approximately 3200 inpatient pediatric hospitalizations (1.9 per 100,000
      population) and 2000 inpatient adult hospitalizations (0.8 per 100,000
      population) for mitochondrial disease in the U.S., with associated direct medical
      costs of $113million. In-hospital mortality rates were 2.4% for children and 3.0%
      for adults, far exceeding population averages. Higher socioeconomic status was
      associated with both having a diagnosis of mitochondrial disease and with higher
      in-hospital mortality. From 2007 to 2011 in California, 495 individuals had at
      least one admission with a diagnosis of mitochondrial disease. Patients had a
      median of 1.1 hospitalizations (IQI, 0.6-2.2) per calendar year of follow-up;
      infants under 2y were hospitalized more frequently than other age groups. Over up
      to five years of follow up, 9.9% of participants with any hospitalization for
      mitochondrial disease were noted to have an in-hospital death. CONCLUSIONS AND
      RELEVANCE: Hospitalizations for pediatric and adult mitochondrial diseases are
      associated with serious illnesses, substantial costs, and significant patient
      time. Identification of opportunities to prevent or shorten such hospitalizations
      should be the focus of future studies.

PMID- 28442182
TI  - A retrospective study: Acute rheumatic fever and post-streptococcal reactive
      arthritis in Japan.
AB  - BACKGROUND: Acute rheumatic fever (ARF) and post-streptococcal reactive arthritis
      (PSRA) are immune-mediated consequences of group A streptococcal pharyngitis. ARF
      has declined in developed nations. No prevalence survey of PSRA has been
      conducted. This study evaluated the incidence and characteristics of ARF and PSRA
      in Japanese children. METHODS: From 2010 to 2015, ARF and PSRA were evaluated
      using clinical data retrospectively collected by chart review from 528 hospitals.
      RESULTS: From 323 hospitals (61% response rate), 44 cases of ARF and 21 cases of
      PSRA were reported. Patients with ARF and/or PSRA were mainly from large cities
      in Japan. The mean age of ARF occurrence was 8.5 years, and the ratio of
      female/male patients was 16:28. Major manifestations in the acute phase included
      carditis, 27 cases (61.4%); polyarthritis, 22 cases (50%); erythema marginatum, 7
      cases (15.9%); Sydenham chorea, 3 cases (6.8%); and subcutaneous nodules, 1 case
      (2.3%). Twenty-one (58.3%) patients had migratory arthritis. During the follow-up
      period, 6 patients (13.6%) showed mild carditis. For PRSA, the mean age was 8.2
      years, and the ratio of female/male patients was 12:9. Six (28.6%) patients had
      monoarthritis, and 4 (19%) patients had migratory arthritis. No patient had
      carditis. CONCLUSIONS: Although ARF and PSRA are rare in the Japanese pediatric
      population, substantial numbers of patients with both conditions were identified
      in this study. We observed a high incidence of arthritis and carditis in ARF
      patients. No PSRA case was complicated with carditis. General pediatricians need
      to have updated information about ARF and PSRA, even in industrialized countries.

PMID- 28442183
TI  - Assessment of Competence in EVAR Stent Graft Sizing and Selection.
AB  - OBJECTIVES AND BACKGROUND: The aims of this study were to develop a test of
      competence in endovascular aortic repair (EVAR) stent graft sizing and selection;
      to examine the test for evidence of validity; and to explore the experience
      required for the task. METHODS: The test was developed based on a literature
      review resulting in 22 anatomical assessment points and a graft selection.
      Validity evidence was explored in an international cross sectional study. Twenty
      two consultants with varying levels of experience in the field (novices,
      intermediates, and experts) were presented with computed tomography angiography
      of the aortic vessels from three patients. Test scores were based on summed z
      scores using the anatomical measurements and graft choices of the experts as a
      reference. A proficiency score was established using the contrasting groups
      standard setting method. RESULTS: The assessment was shown to be reliable with an
      intraclass correlation coefficient of 0.83 (p<.001) and high internal consistency
      with a Cronbach's alpha of .91 (p<.001). Mann-Whitney U test showed that experts
      performed significantly better than novices and intermediates (p<.002 and p<.005,
      respectively). Regarding anatomical measurements, Mann-Whitney U test could
      discriminate between experts and novices (p=.002), between experts and
      intermediates (p=.010), and between novices and intermediates (p=.036). In stent
      selection the experts performed significantly better than both the novices and
      the intermediates (p=.002 and p=.007, respectively), while there was no
      significant difference between the two non-expert groups (p=1). A credible
      passing standard with appropriate consequences was established using the
      contrasting groups methods. CONCLUSION: This study presents a standardised and
      objective assessment tool of competence in vessel analysis and stent graft
      selection for endovascular aortic repair. This was supported by strong validity
      evidence with good internal consistency and discriminatory ability. The tool may
      be used to facilitate training and certification of future endovascular
      specialists.

PMID- 28442184
TI  - Pigmented villonodular synovitis of the knee: A retrospective analysis of 214
      cases at a UK tertiary referral centre.
AB  - AIMS: Pigmented villonodular synovitis (PVNS) is a rare, locally aggressive and
      potentially recurrent synovial disease. We present the largest single-centre
      experience of knee PVNS. Our aim was to evaluate our tertiary hospital's
      experience in the management of knee PVNS. PATIENTS AND METHODS: Retrospective
      data collection of consecutive cases of knee PVNS from 2002 to 2015. RESULTS: In
      total, 214 cases of knee PVNS were identified which represented 53.4% of all PVNS
      (12.1% were recurrent at presentation). 100 were localised PVNS (LPVNS), 114
      diffuse PVNS (DPVNS) and two malignant PVNS. Knee PVNS was more likely to occur
      in females with a mean age of 39. Following surgery, 47.6% had recurrence with
      DPVNS as opposed to 8.6% with LPVNS. In LPVNS, there was no significant
      difference in recurrence between open and arthroscopic synovectomy (8.7% vs 9.1%,
      P>0.05). However, in DPVNS, there was a significantly higher risk of recurrence
      with arthroscopic compared to open synovectomy (83.3% vs 44.8%, RR=1.86 95% CI
      1.32-2.62, P=0.0004). CONCLUSION: PVNS can be difficult to treat. We found no
      difference in local recurrence rates between open and arthroscopic treatment of
      LPVNS but significantly increased rates of recurrence for DPVNS following
      arthroscopic treatment. We would therefore recommend open synovectomy for DPVNS.

PMID- 28442185
TI  - Modified Frailty Index Is an Effective Risk Assessment Tool in Primary Total Knee
      Arthroplasty.
AB  - BACKGROUND: "Frailty" is a marker of physiological decline of multiple organ
      systems, and the frailty index identifies patients who are more susceptible to
      postoperative complications. The purpose of this study is to validate the
      modified frailty index (MFI) as a predictor of postoperative complications,
      reoperations, and readmissions in patients who underwent primary total knee
      arthroplasty (TKA). METHODS: The American College of Surgeons National Surgical
      Quality Improvement Program database from 2005 to 2014 was queried by the Current
      Procedural Terminology code for primary TKA (27447). A previously described MFI
      was used to summate 11 variables in 5 organ systems. Bivariate analysis was
      performed for postoperative complications. A multiple logistic regression model
      was used to determine the relationship between MFI, American Society of
      Anesthesiologists score, and 30-day reoperation, controlling for age, gender, and
      body mass index. RESULTS: A total of 90,260 patients underwent primary TKA during
      the study period. As MFI score increased, 30-day mortality significantly
      increased (P < .001). In addition, significantly higher rates of postoperative
      complications (all P < .001) were observed with increasing MFI: infection, wound,
      cardiac, pulmonary, and renal complications; and any occurrence. More frail
      patients also had increasing odds of adverse hospital discharge disposition,
      reoperation, and readmission (all P < .001). Length of hospital stay increased
      from 3.10 to 5.16 days (P < .001), while length of intensive care unit stay
      increased from 3.47 to 5.07 days (P < .001) between MFI score 0 and >=0.36. MFI
      predicts 30-day reoperation with an adjusted odds ratio of 3.32 (95% confidence
      interval, 1.36-8.11; P < .001). Comparatively, MFI was a stronger predictor of
      reoperation compared with American Society of Anesthesiologists score and age
      with adjustment for gender and body mass index. CONCLUSION: Utilization of the
      MFI is a valid method in predicting postoperative complications, reoperations,
      and readmissions in patients undergoing primary TKA and can provide an effective
      and robust risk assessment tool to appropriately counsel patients and aid in
      preoperative optimization.

PMID- 28442186
TI  - The Acceptability and Potential Utility of Cognitive Training to Improve Working
      Memory in Persons Living With HIV: A Preliminary Randomized Trial.
AB  - HIV-associated neurocognitive impairments that impact daily function persist in
      the era of effective antiretroviral therapy. Cognitive training, a promising low
      cost intervention, has been shown to improve neurocognitive functioning in some
      clinical populations. We tested the feasibility, acceptability, and preliminary
      effects of computerized cognitive training to improve working memory in persons
      living with HIV infection (PLWH) and working memory impairment. In this
      randomized clinical trial, we assigned 21 adult PLWH to either an experimental
      cognitive training intervention or an attention-matched control training
      intervention. Participants completed 12 training sessions across 10 weeks with
      assessments at baseline and post-training. Session attendance was excellent and
      participants rated the program positively. Participants in the experimental arm
      demonstrated improved working memory function over time; participants in the
      control arm showed no change. Our results suggest that cognitive training may be
      a promising intervention for working memory impairment in PLWH and should be
      evaluated further.

PMID- 28442188
TI  - Noninvasive ventilation for ARDS in patients with cancer: Still possible or there
      continues to be a learning curve? In reply.

PMID- 28442187
TI  - HIV Provider Experiences Engaging and Retaining Patients in HIV Care and
      Treatment: "A Soft Place to Fall".
AB  - Engaging and retaining persons with HIV in care and treatment is key to reducing
      new HIV infections in the United States. Understanding the experiences, barriers,
      and facilitators to engaging and retaining persons in HIV care from the
      perspective of HIV care providers could help provide insight into how best to
      achieve this goal. We present qualitative data from 30 HIV care providers in
      three cities. We identified three facilitators to HIV care: providing a medical
      home, team-based care and strategies for engaging and retaining patients in HIV
      care, and focus on provider-patient relationships. We identified two main
      barriers to care: facility-level policies and patient-level challenges. Our
      findings suggest that providers embrace the medical home model for engaging
      patients but need support to identify aspects of the model that promote
      engagement in long-term HIV care, improve the quality of the provider-patient
      relationship, and address persistent logistical barriers, such as transportation.

PMID- 28442190
TI  - Erratum to: Provider Opinions Regarding Expanding Access to Hormonal
      Contraception in Pharmacies [Women's Health Issues 26 (2016) 153-160].

PMID- 28442189
TI  - Exploring How Residents Who Partially Participate in Family Planning Training
      Determine Their Level of Participation.
AB  - OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME)
      requires that obstetrics and gynecology residency programs provide access to
      abortion training, though residents may elect to opt out of participating due to
      religious or moral objections. While clinical benefits of partial participation
      have previously been explored, our study aimed to explore how residents navigate
      partial participation in abortion training and determine their limits. STUDY
      DESIGN: This study was qualitative in nature. Between June 2010 and June 2011, we
      conducted 26 semi-structured phone interviews with residents who opted out of
      some or all of the family planning rotation at 19 programs affiliated with The
      Ryan Residency Training Program. Faculty directors identified eligible residents,
      or residents self-reported in routine program evaluation. We analyzed data using
      the conventional content analysis method. RESULTS: We interviewed all 26 (46%) of
      56 eligible residents willing to be interviewed. Three main categories
      constituted the general concepts concerning resident decision-making in training
      participation: (1) variation in timing of when residents determined the extent of
      participation, (2) a diversity of influences on the residents' level of
      participation, and (3) the perception of support or pressure related to their
      participation decision. CONCLUSIONS: The findings indicated that residents who
      partially participate in abortion training at programs with specialized opt-out
      family planning training weigh many factors when deciding under what
      circumstances, if any, they will provide abortions and participate in training.

PMID- 28442191
TI  - Barriers to Single-Dose Levonorgestrel-Only Emergency Contraception Access in
      Retail Pharmacies.
AB  - OBJECTIVES: In February 2014, the Food and Drug Administration updated its
      regulations to make all single-dose levonorgestrel-only emergency contraception
      (LNG-EC) available over the counter. This study examines the availability and
      access to LNG-EC shortly after this policy change, and any additional barriers to
      obtaining LNG-EC in Colorado retail pharmacies. STUDY DESIGN: From June to July
      2014, three female interviewers posing as women seeking LNG-EC conducted a
      telephone survey of all 633 Colorado retail pharmacies listed in The Little Blue
      Book (2014) phone directory. Completely accessible was defined as LNG-EC
      available on store shelves for purchase without presentation of an ID or
      prescription on the day of the call. RESULTS: Of 633 pharmacies analyzed, 85.0%
      (538/633) were in urban settings and 85.3% (540/633) were chain stores. Eighteen
      of 64 (28.1%) counties in Colorado did not have a pharmacy listed in the phone
      directory. Overall, 86.9% of pharmacies (550/633) had EC in stock on the day of
      contact but only 23.2% (147/633) of these had EC completely accessible. Of
      pharmacies with EC in stock, 41.6% (229/550) kept it behind the counter and 56.0%
      (308/550) required additional documentation to purchase. In stock and completely
      accessible rates were not different across rural, urban, and frontier geographic
      regions within the state (p = .066 and p = .905, respectively), but were
      significantly different across independent, chain, and 24-hour type stores (p <
      .001 and p = .008, respectively). In stock rates were 57.5% (42/73), 90.4%
      (488/540), and 100% (20/20) for independent, chain, and 24-hour stores
      respectively. CONCLUSIONS: Rates of completely accessible LNG-EC are low in
      Colorado despite high rates of availability. Behind-the-counter status and proof
      of-age requirements are identified as the main sources of access restriction in
      Colorado.

PMID- 28442192
TI  - Structural Insights into the Mechanism of Scanning and Start Codon Recognition in
      Eukaryotic Translation Initiation.
AB  - Initiation of translation on eukaryotic mRNAs generally follows the scanning
      mechanism, wherein a preinitiation complex (PIC) assembled on the small (40S)
      ribosomal subunit and containing initiator methionyl tRNAi (Met-tRNAi) scans the
      mRNA leader for an AUG codon. In a current model, the scanning PIC adopts an open
      conformation and rearranges to a closed state, with fully accommodated Met-tRNAi,
      upon AUG recognition. Evidence from recent high-resolution structures of PICs
      assembled with different ligands supports this model and illuminates the
      molecular functions of eukaryotic initiation factors eIF1, eIF1A, and eIF2 in
      restricting to AUG codons the transition to the closed conformation. They also
      reveal that the eIF3 complex interacts with multiple functional sites in the PIC,
      rationalizing its participation in numerous steps of initiation.

PMID- 28442193
TI  - A retrospective institutional study of the association of smoking with the
      severity of hidradenitis suppurativa.

PMID- 28442194
TI  - A child abuse research network: Now what?
AB  - As foundational work in preparation for a sustainable, multi-center network
      devoted to child abuse medical research, we recently used a combination of survey
      and modified Delphi methodologies to determine research priorities for future
      multi-center studies. Avoiding missed diagnoses, and improving selected/indicated
      prevention were the topics rated most highly in terms of research priority.
      Several constructive commentaries in this issue identify the key challenges which
      must be overcome to ensure a successful network. Indeed, as with the clinical
      work of child abuse pediatrics, a scientific network will also require constant
      collaboration within and outside the community of child abuse pediatricians, the
      wider medical community, and even non-medical professions.

PMID- 28442195
TI  - Changing attitudes about spanking among conservative Christians using
      interventions that focus on empirical research evidence and progressive biblical
      interpretations.
AB  - This study examined how interventions that include either empirical research
      evidence about spanking, progressive biblical interpretations, or both, affect
      attitudes and intentions about spanking. A sample of 129 college students (70%
      female; 30% male; Mage=19) attending a private, Christian university was randomly
      assigned to one of three intervention conditions: (1) Research Only, (2) Religion
      Only, or (3) Research and Religion. Four weeks prior to the intervention
      sessions, students completed a Demographic Form, the Religious Fundamentalism
      Scale, and the Attitudes Toward Spanking (ATS) scale. Following the intervention,
      students completed the ATS scale a second time. A two-way ANOVA indicated a
      significant main effect for the intervention condition and an interaction effect
      between intervention condition and religious fundamentalism, indicating that
      positive spanking attitudes declined most significantly in the Research and
      Religion intervention condition (F(2, 123)=4.05, p=.02, hp2=.06) with the
      greatest change in attitudes among the Religious Fundamentalism Group in that
      condition (F(2, 123)=4.50, p=.01, hp2=.07). A second two-way ANOVA indicated a
      significant main effect for Conservative Protestant Affiliation (F(2, 123)=4.39,
      p=.04, hp2=.03) indicating that positive spanking attitudes declined most
      significantly for participants identifying with a conservative religious
      affiliation. Overall, the findings suggest that, especially among Conservative
      Protestants, interventions that focus on both empirical research and progressive
      biblical interpretations of scripture can reduce positive attitudes toward, and
      intentions to use, spanking. This study has implications for decreasing spanking
      use among Conservative Christians and for the development of training programs to
      reduce parents' use of spanking.

PMID- 28442196
TI  - Mechanism of neuronal activity and synaptic transmission in rostral ventrolateral
      medulla.
AB  - Rostral ventrolateral medulla (RVLM) plays an essential role in blood pressure
      homeostasis. This study was aimed to investigate the mechanism of neuronal
      activity and synaptic transmission in the RVLM. Medulla oblongata slices were
      carefully obtained from brainstem of rats. With continues perfusion of artificial
      cerebrospinal fluid (ACSF), the spontaneous firing of slices and amplitudes were
      assayed by conventional whole cell patch-clamp recording after addition of gamma
      aminobutyric acid (GABA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA) and N-methyl d-aspartate (NMDA). Furthermore, the effects of agonist or
      antagonist targeted Type-A GABA (GABAA) or glutamate receptors on spontaneous
      excitatory postsynaptic potential (sEPSP) and spontaneous inhibitory postsynaptic
      potential (sIPSP) of neurons in RVLM were determined. The spontaneous firing of
      neurons in RVLM were inhibited by GABA (P<0.001) while were promoted by NMDA or
      AMPA (P<0.01 or P<0.001). In terms of sEPSP and sIPSP, the numbers of firing
      neurons in RVLM were both improved by GABAA receptor antagonist (P<0.01 or
      P<0.001) while were both decreased by GABAA receptor agonist or glutamate
      receptor antagonist (P<0.05, P<0.01 or P<0.001). The corresponding effects of
      agonist and antagonist on amplitudes were the same as the effects on number of
      firing neurons in RVLM. The spontaneous firing, sEPSP and sIPSP of neurons in
      RVLM were all activated by GABAA receptor antagonist while were all suppressed by
      GABAA receptor agonist or glutamate receptor antagonist.

PMID- 28442197
TI  - Metastases in cerebellopontine angle from the tumors of central nerve system.
AB  - The objective of this study was to analyze the characters of the cerebellopontine
      angle (CPA) metastases from central nerve system (CNS) tumors. Ten patients were
      reviewed for the period between 2008 and 2015. The clinical and neuroimaging
      features, and treatment outcomes were analyzed retrospectively. The average
      period during primary diagnosis through the diagnosis of CPA metastases was
      42.4months. Among the 10 cases, the primary tumors and metastases were found
      simultaneously in 3 cases, the metastases after primary tumor removal were found
      in 5 cases, and the metastases after stereotaxic radiosurgery were found in 2
      cases. Only 4 patients presented with the symptoms and signs associated with CPA
      involving, one with hearing loss, one presenting facial paralysis, one suffering
      from tinnitus and one case with dizziness. There were 2 cases with the miliary
      metastases and 8 cases with massive metastases. There existed 3 cases with single
      CPA metastases, whereas 7 cases with multiple metastatic foci. Among the 8 cases
      of massive metastatic foci, 6 tumors presented the solid features and the other 2
      cases exhibited cystic and solid features. In this cohort of cases, 4 cases were
      involved in the bilateral and 6 cases presented unilateral metastatic foci. The
      three CPA metastases were removed in this group, 6 case performed with
      radiotherapy, and 5 cases received chemotherapy. In the current group 5 patients
      have been dead, 3 patients kept stable and 2 cases experienced improvement. In
      spite of seldom previous reports regarding the metastases from CNS tumors
      occurring in the CPA are existent, this rare form of the disease should be
      considered in future evaluation as a differential diagnosis.

PMID- 28442198
TI  - Operational oil spill trajectory modelling using HF radar currents: A northwest
      European continental shelf case study.
AB  - This paper presents a novel operational oil spill modelling system based on HF
      radar currents, implemented in a northwest European shelf sea. The system
      integrates Open Modal Analysis (OMA), Short Term Prediction algorithms (STPS) and
      an oil spill model to simulate oil spill trajectories. A set of 18 buoys was used
      to assess the accuracy of the system for trajectory forecast and to evaluate the
      benefits of HF radar data compared to the use of currents from a hydrodynamic
      model (HDM). The results showed that simulated trajectories using OMA currents
      were more accurate than those obtained using a HDM. After 48h the mean error was
      reduced by 40%. The forecast skill of the STPS method was valid up to 6h ahead.
      The analysis performed shows the benefits of HF radar data for operational oil
      spill modelling, which could be easily implemented in other regions with HF radar
      coverage.

PMID- 28442199
TI  - Tissue concentrations of four Taiwanese toothed cetaceans indicating the silver
      and cadmium pollution in the western Pacific Ocean.
AB  - Muscle, lung, kidney and liver tissues of 45 bycatch and stranded cetaceans,
      including 14 Grampus griseus (Gg), 7 Kogia simus (Ks), 10 Lagenodelphis hosei
      (Lh), and 14 Stenella attenuata (Sa), were collected in the waters off Taiwan
      from 1994 to 1995, and from 2001 to 2012. Baseline concentrations (in MUgg-1 dry
      weight) of the cetaceans were lung (<0.05)=muscle (<0.05)<kidney (0.08+/
      0.04)<liver (0.43+/-0.28) for Ag, and muscle (0.03+/-0.03)=lung (0.22+/
      0.19)<liver (3.82+/-3.50)<kidney (16.22+/-18.81) for Cd. Unhealthy and critically
      dangerous Ag and Cd tissue concentrations in the toothed cetaceans are suggested.
      Marked high concentrations of Ag and Cd found in Gg and Lh are highly related to
      their squid-eating and deep diving habits. The highest ever recorded
      concentrations of liver-Ag and kidney-Cd were found in two Lh. These Taiwanese
      cetaceans indicate marked Ag and Cd pollution in the recent two decades in the
      western Pacific Ocean.

PMID- 28442200
TI  - Next-generation sequencing and culture-based techniques offer complementary
      insights into fungi and prokaryotes in beach sands.
AB  - A next-generation sequencing (NGS) approach, in conjunction with culture-based
      methods, was used to examine fungal and prokaryotic communities for the presence
      of potential pathogens in beach sands throughout Portugal. Culture-based fungal
      enumeration revealed low and variable concentrations of the species targeted
      (yeasts and dermatophytes), which were underrepresented in the community
      characterized by NGS targeting the ITS1 region. Conversely, NGS indicated that
      the potentially pathogenic species Purpureocillium liliacinum comprised nearly
      the entire fungal community. Culturable fecal indicator bacterial concentrations
      were low throughout the study and unrelated to communities characterized by NGS.
      Notably, the prokaryotic communities characterized revealed a considerable
      abundance of archaea. Results highlight differences in communities between
      methods in beach sand monitoring but indicate the techniques offer complementary
      insights. Thus, there is a need to leverage culture-based methods with NGS
      methods, using a toolbox approach, to determine appropriate targets and metrics
      for beach sand monitoring to adequately protect public health.

PMID- 28442201
TI  - Temporal variations in physiological responses of Kandelia obovata seedlings
      exposed to multiple heavy metals.
AB  - A study was conducted to quantify temporal variations in physiological responses
      of Kandelia obovata under multiple heavy metal stress. The results showed that
      plant growth was not significantly affected by multiple heavy metal stress during
      the 120-days experiment. At the start, levels of net photosynthetic rate (Pn),
      stomatal conductance (Gs) and transpiration rate (Tr) showed effects of "low
      promotion, high-inhibition", but Pn and Gs reduced with increasing heavy metal
      stress at the end. Temporary lipid oxidation was shown by high levels of
      malondialdehyde (MDA) under high heavy metal stress at the start but was
      unaffected at the end of the experiment. MDA negatively correlated with biomass
      and photosynthetic parameters and acted as a sensitive indicator. Proline also
      shared similar trend and indicated its temporary role in osmotic adjustment.
      Negative correlations between osmotic adjustment matter and photosynthetic
      parameters further confirmed the significant role of osmotic adjustment under
      heavy metal stress.

PMID- 28442202
TI  - Macrobenthic communities in Hong Kong waters: Comparison between 2001 and 2012
      and potential link to pollution control.
AB  - Macrobenthic communities in 2001 and 2012 were compared across the marine
      environment of Hong Kong based on sediment grab samples collected from 28
      stations. CLUSTER analysis showed in both surveys that the stations could be
      divided into four groups at 20% faunal similarity. However, there were notable
      changes in the macrobenthic community structure between 2001 and 2012 in three
      focal areas of pollution control (i.e., Victoria Harbour, Deep Bay and Tolo
      Harbour). The potential link between macrobenthos and pollution abatement
      measures, and the contributions of environmental conditions to the differential
      responsiveness of macrobenthos were explored. Notably, a reduction in nutrient
      input to the eastern part of Victoria Harbour might have led to recovery of
      benthic communities therein.

PMID- 28442203
TI  - Patterns of health care use of injured adults: A population-based matched cohort
      study.
AB  - BACKGROUND: Healthcare use by traumatically injured individuals prior to and
      subsequent to their injury are not often explored for different types of
      injuries. This study aims to describe health care use 12 months preceding and 12
      months following a traumatic injury by injury type and injury severity. METHOD:
      Hospital and mortality data from three Australian states were linked in a
      population-based matched cohort study. Individuals >=18 years who had an injury
      related hospital admission in 2009 were identified as the injured cohort. A
      comparison cohort of non-injured people, matched 1:1 on age, gender and postcode
      of residence, was randomly selected from the electoral roll. Twelve-month pre-
      and post-index injury health service use was examined. Rates, adjusted rate
      ratios and attributable risk proportions were calculated by injury type and
      severity. RESULTS: The injury cohort experienced higher 12-month pre- and post
      injury hospital admissions than the non-injured group. By 6 to 7 months post
      injury, the injury cohort had largely returned to their pre-injury health service
      use levels, except for injuries involving dislocations, sprains and strains and
      injury to nerves and spinal cord. Hip fracture (17.69 per 100 person-months) and
      poisoning (16.09 per 100 person-months) had the highest rates of post-injury
      hospitalisation in the injured cohort. The adjusted rate ratios (ARR) for post
      injury hospitalisation were highest for poisoning (ARR: 3.77; 95% CI: 3.38-4.21)
      and injury to nerves and spinal cord (ARR: 2.73; 95% CI: 2.27-3.28). Poisoning
      also had the highest ARR for post-injury LOS (ARR: 5.31; 95% CI: 4.51-6.27).
      CONCLUSIONS: After sustaining a traumatic injury, many individuals are readmitted
      to hospital and require ongoing care up to 12 months post-injury. That injured
      individuals post-injury largely return to their pre-index injury hospital use by
      6 to 7 months could imply a return to pre-injury function and/or that other
      measures of health service use should be explored. Trauma services should
      consider long-term follow-up and support services for seriously injured patients
      post-hospital discharge.

PMID- 28442204
TI  - Out of hospital thoracotomy for cardiac arrest after penetrating thoracic trauma.
AB  - INTRODUCTION: Emergency department thoracotomy is an established procedure for
      cardiac arrest in patients suffering from penetrating thoracic trauma and yields
      relatively high survival rates (up to 21%) in patients with cardiac tamponade. To
      minimize the delay between arrest and thoracotomy, some have advocated
      thoracotomy on the accident scene. The aim of this study was to determine the
      proportion of patients with return of spontaneous circulation and subsequent
      survival after out of hospital thoracotomy in the Netherlands. METHODS: A
      retrospective analysis of data collected on all out of hospital thoracotomies
      performed in the Netherlands after penetrating trauma between April 1st, 2011 and
      September 30th, 2016 was performed. Data on patient characteristics, trauma
      mechanism and outcome were collected and analyzed. Primary outcome measure was
      return of spontaneous circulation after the intervention. Survival to hospital
      discharge was the secondary outcome variable. RESULTS: Thirty-three prehospital
      emergency thoracotomies were performed. Ten patients (30%) had gunshot wounds and
      23 patients (70%) had stab wounds. Nine patients (27%) had return of spontaneous
      circulation and were presented to the hospital. Of these, one patient survived
      until discharge without neurological damage. Five died in the emergency
      department or operating room and three died in ICU. CONCLUSION: Return of
      spontaneous circulation after out of hospital thoracotomy for cardiac arrest due
      to penetrating thoracic injury is achievable, but a substantial number of
      patients die during the in hospital resuscitation phase. However, neurologic
      intact survival can be achieved.

PMID- 28442205
TI  - Litigation related to casting in Orthopaedics-An analysis of claims against the
      National Health Service in England.
AB  - Orthopaedic casts have been used to treat musculoskeletal conditions for hundreds
      of years and are still a fundamental component of treating a variety of
      disorders. As surgical techniques have advanced the frequency of use of
      orthopaedic casts has declined. With Orthopaedics being is one of the most
      litigious specialties in medicine we sough to evaluate how this related to
      casting in Orthopaedics and how we could learn from past mistakes. We analysed
      litigation claims related to Orthopaedic casts from 1995 to 2010 in which the
      claims were closed. 43 cases were related to orthopaedic casts. The total costs
      of these claims were over L2.3 million with an average total cost of L48,500 per
      claim. The most common cause for claim was harm caused when a cast was applied
      too tight and secondly from removing the cast. This is the first study to
      evaluate litigation claims related to Orthopaedic casts and highlights potential
      complications that if avoided will certainly improve the care of the patients and
      avoid unnecessary litigation.

PMID- 28442206
TI  - Change the habit to change the practice: Do audits really ever change anything?
AB  - INTRODUCTION: Methicillin resistant staphylococcus aureus (MRSA) eradication by
      nurses and pre-op induction antibiotics are mandated for emergency surgery, where
      true status is unknown. We assessed adherence to local MRSA guidelines for
      patients undergoing emergency hip fracture surgery and employed point of decision
      prompts to influence clinicians' behaviour. METHODS: We undertook a retrospective
      record review for all patients undergoing emergency hip fracture surgery at a UK
      major trauma centre over 3-months. Demographics, MRSA eradication therapy and
      antibiotics were recorded. Admission-to-MRSA swab result time was compared to the
      admit-to-operation time. Posters on induction antibiotics were placed in
      anaesthetic rooms, stickers on MRSA eradication therapy on nursing care bundles
      and standards re-audited after 6 months. RESULTS: The case-mix was similar in
      both audit cycles: initial audit (n=69, mean age 76.9, range 33-94), re-audit
      (n=77, mean age 73.8, range 18-95). There was a small rise in adherence to
      eradication therapy prescription (1% vs 8%) after sticker distribution, although
      compliance was poor pre and post intervention. Correct antibiotic choice for MRSA
      unknown patients (18% vs 94%) improved significantly after poster intervention.
      Operations occurred at a median of 24.05h (Q1 17.6, Q3 32.3) from admission but
      MRSA swab results returned at a median of 48h (Q1 41.5, Q3 59.5) p=<0.0001.
      CONCLUSION: Providing reminders at the points where decisions are to be made are
      effective. Audit interventions should be easily undertaken and will become
      habitual if connected in sequence to old behaviours.

PMID- 28442207
TI  - Tibio-talo-calcaneal fusion after limb salvage procedures-A retrospective study.
AB  - BACKGROUND: The treatment of limb threatening trauma on the distal tibia or
      hindfoot often results in posttraumatic osteoarthritis requiring
      tibiotalocalcaneal (TTC) arthrodesis. The purpose of this study was to present a
      case series of patients undergoing various techniques of joint fusion after bone
      reconstruction and deformity correction as a salvage procedure. The study should
      help trauma surgeons making decisions in limb salvage and deformity correction in
      complex lower leg and foot injuries by presenting options and treatment
      strategies. PATIENTS AND METHODS: Eight patients (4 male, 4 female) after TTC
      arthrodesis as a definitive procedure after polytrauma or monotrauma involving
      the distal tibia or hindfoot were the subject of this retrospective analysis. We
      included patients treated by external ring fixation (1 case), external
      fixation+wires (1 case), external fixation+screws (1 case) and intramedullary
      nailing (1 ante- and 5 retrograde; 1 bilateral, 4 unilateral). Initial trauma
      included open fractures, subtotal foot amputations and closed fractures with
      failed osteosynthesis and failed ankle joint replacement. Bone defects were
      treated with callus distraction or segment transport in 5 cases. Various angles
      were measured to assess foot deformities in the lateral radiographic view and
      clinical results were presented. RESULTS: Independent, pain-free mobilisation
      with full weight bearing was achieved in all 8 patients. In terms of subjective
      outcome, all patients reported a highly satisfying result. Complete consolidation
      at the fusion site was achieved in 8 out of 9 cases with a high rate of adjacent
      joint arthritis. Angles measures in the lateral radiographs showed values typical
      for a pes cavus tendency. CONCLUSION: Tibio-talo-calcaneal (TTC) arthrodesis is a
      viable treatment option for severe post traumatic arthritis and deformity of the
      ankle and subtalar joint. Despite bad bone quality retrograde intramedullary
      nailing does provide acceptable results providing stability, low invasiveness and
      low infection rate. Simultaneous TTC-fusion and tibial lengthening using the
      Ilizarov ring fixator may be necessary when the surgeon is confronted with large
      bone defects - often followed by a nailing after lengthening procedure. This
      study shows that limb preservation after limb threatening trauma with hindfoot
      injury and multiple fractures of the lower extremity is recommenced as the method
      of choice with reasonable clinical results. LEVEL OF EVIDENCE: IV, Case series.

PMID- 28442208
TI  - Parotid gland involvement as an initial presentation of papillary thyroid
      carcinoma.
AB  - Papillary thyroid carcinoma (PTC) is the most differentiated malignant thyroid
      neoplasm. Local metastases of PTC commonly occur in the regional lymph nodes,
      while distant metastases are mainly to the lung and bone. The case of a patient
      with PTC who presented with swelling of the parotid gland and neck, mimicking a
      primary parotid neoplasm, is presented herein. This case is unique due to the
      unexpected initial presentation of PTC with no signs of disease in the thyroid
      gland.

PMID- 28442209
TI  - Letter from the Editors.

PMID- 28442210
TI  - Issues of Survivorship and Rehabilitation in Soft Tissue Sarcoma.
AB  - As the number of survivors of extremity soft tissue sarcoma increases, so does
      the need to understand the experience of survivors and develop measures, systems
      and services that support rehabilitation into normal life roles. Survivorship
      includes considerations of the physical, psychological and social domains, of
      which the physical sequelae of treatment are the best characterised in the
      literature. The survivorship experience may include disability, pain,
      lymphoedema, psychological problems, as well as difficulty with employment,
      relationships and lower quality of life. Rehabilitation strategies for extremity
      sarcoma patients must be personalised, holistic and begin early in the pathway,
      ideally before the first treatment intervention. The International Classification
      of Functioning, Disability and Health model is a useful framework for combining
      assessments, including objective outcome measures, which can be combined into a
      rehabilitation prescription. Research is needed to develop an evidence base for
      rehabilitation interventions to support patients with extremity soft tissue
      sarcoma.

PMID- 28442211
TI  - Leigh-like neuroimaging features associated with new biallelic mutations in OPA1.
AB  - Behr syndrome is characterized by the association of early onset optic atrophy,
      cerebellar ataxia, pyramidal signs, peripheral neuropathy and mental retardation.
      Recently, some cases were reported to be caused by biallelic mutations in OPA1.
      We describe an 11-year-old girl (Pt1) and a 7-year-old boy (Pt2) with cognitive
      delay, ataxic gait and clinical signs suggestive of a peripheral neuropathy, with
      onset in early infancy. In Pt1 ocular fundus examination revealed optic disk
      pallor whereas Pt2 exhibited severe optic atrophy. In both children neuroimaging
      detected a progressive cerebellar involvement accompanied by basal ganglia
      hyperintensities and pathological peak levels of lactate. In both patients,
      muscle biopsy showed diffuse reduction of cytochrome c oxidase stain, some
      atrophic fibers and type II fiber grouping. Using a targeted resequencing panel
      in next generation sequencing, we identified the homozygous c.1180G>A/p.Ala394Thr
      mutation in Pt1 and the c.2779-2A>C mutation in compound heterozygosity with the
      c.2809C>T/p.Arg937Cys mutation in Pt2. All variants were novel and segregated in
      the healthy parents. Expression of OPA1 protein was significantly reduced in
      muscle tissues of both patients by Western blotting. We also observed in
      patients' fibroblasts a higher proportion of fragmented and intermediate
      mitochondria upon galactose treatment compared to controls, as already seen in
      other patients harboring mutations in OPA1. The presence of Leigh-like
      neuroimaging features is a novel finding in Behr syndrome and further adds to the
      complex genotype-phenotype correlations in OPA1-associated disorders.

PMID- 28442212
TI  - Effects of underwater ultrasound therapy on pain, inflammation, hand function and
      quality of life in patients with rheumatoid arthritis - a randomized controlled
      trial.
AB  - OBJECTIVES: To investigate the effects of underwater ultrasound (US) therapy in
      48 patients with moderately active rheumatoid arthritis (disease activity score
      in 28 joints [DAS28]>3.2 and<5.1). METHODS: Patients randomly assigned to the
      ultrasound group (n=25) received underwater continuous ultrasound therapy to both
      wrists and hands for 7min per session with an intensity of 0.7W/cm2 for 10
      sessions. The control group (n=23) received sham treatment under the same
      conditions. At baseline, at the end of treatment (end of Week 2) and at the
      follow-up visit (Week 14), the following outcomes were evaluated: disease
      activity (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], tender
      and swollen joint counts, pain on a visual analog scale, DAS28, hand function
      (fist making, wrist extension and flexion, hand grip strength) and quality of
      life (Health Assessment Questionnaire [HAQ]). RESULTS: A significant decrease in
      C-reactive protein at the end of Week 2 and Week 14 compared to control group
      (mean between-group difference at 2 weeks=-5.77, 95% CI=-10.86 to -0.68, mean
      between-group difference at 14 weeks=-5.07, 95% CI=-10.13 to -0.01), and non
      significant decrease in DAS28 was observed. By the end of treatments at the end
      of week 2, ultrasound alleviated pain significantly (mean between-group
      difference at two weeks=-8.35 95% CI=-16.12 to -0.58), as well as improved left
      wrist extension compared to the control group (mean between-group difference at
      14 weeks=4.35, 95% CI=1.09-7.60). CONCLUSION: Underwater ultrasound therapy was
      better than sham treatment at the end of 2 weeks of treatment, but not at long
      term (14 weeks) in patients with rheumatoid arthritis. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT02706028
      (https://clinicaltrials.gov/ct2/show/NCT02706028).

PMID- 28442214
TI  - Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.
AB  - Novel concepts in immunometabolism support the hypothesis that glucose
      consumption is also used to modulate anti-tumor immune responses, favoring growth
      and expansion of specific cellular subsets defined in the past as suppressor T
      cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto
      Warburg and colleagues observed that tumors consumed high amounts of glucose
      compared to normal tissues, even in the presence of oxygen and completely
      functioning mitochondria. However, the role of the Warburg Effect is still not
      completely understood, particularly in the context of an ongoing anti-tumor
      immune response. Current experimental evidence suggests that tumor-derived
      metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance.
      For example, several glycolytic enzymes, deregulated in cancer, contribute to
      tumor progression independently from their canonical metabolic activity. Indeed,
      they can control apoptosis, gene expression and activation of specific
      intracellular pathways, thus suggesting a direct link between metabolic switches
      and pro-tumorigenic transcriptional programs. Focus of this review is to define
      the specific metabolic pathways controlling Treg cell immunobiology in the
      context of anti-tumor immunity and tumor progression.

PMID- 28442215
TI  - [Neopterin levels and systemic inflammatory response syndrome in pediatric
      critically ill patients].
AB  - INTRODUCTION: Neopterin and biopterin are sub-products of redox reactions, which
      act as cofactors of enzymes responsible for nitric oxide production. The
      hypothesis is presented that plasma neopterin and biopterin evolve differently
      during the first days in a critically ill child. METHODS: A single-centre
      prospective observational study was conducted on patients 7 days to 14 years
      admitted to our Paediatric Intensive Care Unit (PICU) and that met Systemic
      inflammatory response syndrome (SIRS) criteria. Neopterin and biopterin levels,
      as well as other acute phase reactants, were collected at admission and at 24 h.
      RESULTS: A total of 28 patients were included, of which 78.9% were male, The
      median age was 5.04 years (interquartile range [IQR] 1.47-10.26), and PRISM II
      2.0% (IQR 1.1-5.0). Mechanical ventilation (MV) was used in 90% of patients, with
      a median duration of 6.0 hrs (IQR 3.7-102.0). The median length of stay in PICU
      was 5.0 days (IQR 2.7-18.7), maximum VIS mean of 0 (IQR 0-14). Baseline neopterin
      level was 2.3+/-1.2 nmol/l and at 24 h it was 2.3+/-1.4 nmol/l. Baseline
      biopterin was 1.3+/-0.5 nmol/l and 1.4+/-0.4 nmol/l at 24 h. Neopterin levels
      were significantly higher in patients with PICU length of stay > 6 days (P=.02),
      patients who needed MV >24 h (P=.023), and those who developed complications
      (P=.05). Neopterin correlates directly and is statistically significant with the
      duration of MV (rho=.6, P=.011), PICU length of stay (rho=.75, P<.0001), and VIS
      (rho=.73, P=.001). Additionally, biopterin directly correlates with the PRISM
      (rho=.61, P=.008). DISCUSSION: There is a higher neopterin level when there is a
      longer PICU stay, higher VIS score, longer time on MV, and occurrence of
      complications, indicating the involvement of an activation of the cellular immune
      system.

PMID- 28442216
TI  - TREM2, Microglia, and Neurodegenerative Diseases.
AB  - Alzheimer's disease (AD) is the most common form of dementia and the 6th leading
      cause of death in the US. The neuropathological hallmarks of the disease are
      extracellular amyloid-beta (Abeta) plaques and intraneuronal hyperphosphorylated
      tau aggregates. Genetic variants of TREM2 (triggering receptor expressed on
      myeloid cells 2), a cell-surface receptor expressed selectively in myeloid cells,
      greatly increase the risk of AD, implicating microglia and the innate immune
      system as pivotal factors in AD pathogenesis. Recent studies have advanced our
      understanding of TREM2 biology and microglial activities in aging and
      neurodegenerative brains, providing new insights into TREM2 functions in amyloid
      plaque maintenance, microglial envelopment of plaque, microglia viability, and
      the identification of novel TREM2 ligands. Our increased understanding of TREM2
      and microglia has opened new avenues for therapeutic intervention to delay or
      prevent the progression of AD.

PMID- 28442217
TI  - Vasculopathic and vasculitic dermatoses.
AB  - The inflammatory and non-inflammatory disorders affecting the blood vessels are
      an important cause of death among patients. Additionally, some of the findings
      could be very subtle, while the consequences of misdiagnosis tragic. There is a
      limited number of factors by which the cutaneous blood vessels can be affected
      and the most common examples in the clinical practice will be discussed here: non
      inflammatory purpuras; vascular-occlusive disorders; urticarias; vasculitides;
      and neutrophilic dermatoses.

PMID- 28442213
TI  - Pathogenic CD4+ T cells in patients with asthma.
AB  - Asthma encompasses a variety of clinical phenotypes that involve distinct T cell
      driven inflammatory processes. Improved understanding of human T-cell biology and
      the influence of innate cytokines on T-cell responses at the epithelial barrier
      has led to new asthma paradigms. This review captures recent knowledge on
      pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse
      models and human disease. In patients with allergic asthma, TH2 cells promote IgE
      mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss
      recent discoveries in the myriad molecular pathways that govern the induction of
      TH2 differentiation and the critical role of GATA-3 in this process. We elaborate
      on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid
      cells translates to T-cell outcomes, with an emphasis on the actions of thymic
      stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts
      on how T-cell skewing and epitope specificity are shaped by multiple
      environmental cues integrated by dendritic cell "hubs" are discussed. We also
      describe advances in understanding the origins of atypical TH2 cells in asthmatic
      patients, the role of TH1 cells and other non-TH2 types in asthmatic patients,
      and the features of T-cell pathogenicity at the single-cell level. Progress in
      technologies that enable highly multiplexed profiling of markers within a single
      cell promise to overcome barriers to T-cell discovery in human asthmatic patients
      that could transform our understanding of disease. These developments, along with
      novel T cell-based therapies, position us to expand the assortment of molecular
      targets that could facilitate personalized treatments.

PMID- 28442218
TI  - Alignment of the transcriptome with individual variation in animals selectively
      bred for High Drinking-In-the-Dark (HDID).
AB  - Among animals at risk for excessive ethanol consumption such as the HDID selected
      mouse lines, there is considerable individual variation in the amount of ethanol
      consumed and the associated blood ethanol concentrations (BECs). For the HDID
      lines, this variation occurs even though the residual genetic variation
      associated with the DID phenotype has been largely exhausted and thus is most
      likely associated with epigenetic factors. Here we focus on the question of
      whether the genes associated with individual variation in HDID-1 mice are
      different from those associated with selection (risk) (Iancu et al., 2013).
      Thirty-three HDID-1 mice were phenotyped for their BECs at the end of a standard
      DID trial, were sacrificed 3 weeks later, and RNA-Seq was used to analyze the
      striatal transcriptome. The data obtained illustrate that there is considerable
      overlap of the risk and variation gene sets, both focused on the fine-tuning of
      synaptic plasticity.

PMID- 28442219
TI  - Virulence potential of Staphylococcus aureus isolates from Buruli ulcer patients.
AB  - Buruli ulcer (BU) is a necrotizing infection of the skin and subcutaneous tissue
      caused by Mycobacterium ulcerans. BU wounds may also be colonized with other
      microorganisms including Staphylococcus aureus. This study aimed to characterize
      the virulence factors of S. aureus isolated from BU patients. Previously
      sequenced genomes of 21 S. aureus isolates from BU patients were screened for the
      presence of virulence genes. The results show that all S. aureus isolates
      harbored on their core genomes genes for known virulence factors like alpha
      hemolysin, and the alpha- and beta-phenol soluble modulins. Besides the core
      genome virulence genes, mobile genetic elements (MGEs), i.e. prophages, genomic
      islands, pathogenicity islands and a Staphylococcal cassette chromosome (SCC)
      were found to carry different combinations of virulence factors, among them genes
      that are known to encode factors that promote immune evasion, superantigens and
      Panton-Valentine Leucocidin. The present observations imply that the S. aureus
      isolates from BU patients harbor a diverse repertoire of virulence genes that may
      enhance bacterial survival and persistence in the wound environment and
      potentially contribute to delayed wound healing.

PMID- 28442220
TI  - A Laparoscopic Approach is Best for Retroperitoneal Lymph Node Dissection: No.

PMID- 28442221
TI  - A Laparoscopic Approach is Best for Retroperitoneal Lymph Node Dissection: Yes.

PMID- 28442222
TI  - Reply by Authors.

PMID- 28442224
TI  - Functional hyperconnectivity vanishes in children with developmental dyscalculia
      after numerical intervention.
AB  - Developmental dyscalculia (DD) is a developmental learning disability associated
      with deficits in processing numerical and mathematical information. Although
      behavioural training can reduce these deficits, it is unclear which neuronal
      resources show a functional reorganization due to training. We examined typically
      developing (TD) children (N=16, mean age: 9.5 years) and age-, gender-, and
      handedness-matched children with DD (N=15, mean age: 9.5 years) during the
      performance of a numerical order task with fMRI and functional connectivity
      before and after 5-weeks of number line training. Using the intraparietal sulcus
      (IPS) as seed region, DD showed hyperconnectivity in parietal, frontal, visual,
      and temporal regions before the training controlling for age and IQ.
      Hyperconnectivity disappeared after training, whereas math abilities improved.
      Multivariate classification analysis of task-related fMRI data corroborated the
      connectivity results as the same group of TD could be discriminated from DD
      before but not after number line training (86.4 vs. 38.9%, respectively). Our
      results indicate that abnormally high functional connectivity in DD can be
      normalized on the neuronal level by intensive number line training. As functional
      connectivity in DD was indistinguishable to TD's connectivity after training, we
      conclude that training lead to a re-organization of inter-regional task
      engagement.

PMID- 28442223
TI  - Diurnal cortisol after early institutional care-Age matters.
AB  - Several studies have shown that young children who have experienced early
      caregiving adversity (e.g. previously institutionalization (PI)) exhibit
      flattened diurnal cortisol slopes; however, less is known about how these
      patterns might differ between children and adolescents, since the transition
      between childhood and adolescence is a time of purported plasticity in the
      hypothalamic-pituitary-adrenal (HPA) axis. PI youth experience a massive
      improvement in caregiving environment once adopted into families; therefore we
      anticipated that a developmental increase in HPA axis plasticity during
      adolescence might additionally allow for an enhanced enrichment effect by the
      adoptive family. In a cross-sectional sample of 197 youths (PI and Comparison; 4
      15 years old) we observed age-related group differences in diurnal slope. First
      replicating previous findings, PI children exhibited flattened diurnal slope.
      This group difference, however, was not observed in adolescents. Moderation
      analyses showed that pubertal development, increased time with family, and early
      adoption contributed to the steeper diurnal cortisol slope in PI adolescents.
      These findings add support to existing theories positing that the transition
      between middle childhood and adolescence may mark an additional sensitive period
      for diurnal cortisol patterning, allowing PI youth to benefit from the enriched
      environment provided by adoptive parents during this period of development.

PMID- 28442225
TI  - Hypoglycaemia and brief interventions in the emergency department - A systematic
      review.
AB  - OBJECTIVE: For people with diabetes, severe hypoglycaemia is the most common
      reason for emergency service usage and emergency department (ED) presentations.
      Brief interventions (BI) are a recognised intervention strategy in the ED for
      other conditions but to date, they have not been applied to those with
      hypoglycemia. This review aims to identify components and outcomes of BI for
      people with diabetes mellitus to inform the development of BI in the ED. METHOD:
      A systematic review of randomized controlled trials was undertaken in MEDLINE,
      CINAHL, PsychINFO and EMBASE. Studies that examined brief interventions for
      people with diabetes were considered. Eligible studies were critically appraised
      and included in a narrative synthesis. RESULTS: A total of 2475 citations were
      identified, 171 full papers were reviewed and four articles were included for
      review. The components 'advice' and 'assistance' from the five A Framework were
      the most frequently used BI components. Statistically significant improvements
      were achieved in psychological, functional, and satisfaction outcomes. However,
      clinical outcomes were not improved and economic outcomes like costs of BI were
      not evaluated. CONCLUSIONS: The literature review demonstrated a lack of evidence
      related to BI in diabetes within the emergency setting despite the ED being an
      ideal environment. Future research needs to be conducted to investigate the
      effectiveness of BI for patients with diabetes.

PMID- 28442226
TI  - Female athlete triad: At breaking point.

PMID- 28442227
TI  - Laparoscopic Versus Percutaneous Cryoablation of Small Renal Mass: Systematic
      Review and Cumulative Analysis of Comparative Studies.
AB  - The objective of this study was to compare the surgical, oncological, and
      functional outcomes of laparoscopic and percutaneous cryoablation for the
      treatment of small renal masses. A systematic review of the literature was
      performed through March 2016 using PubMed, Scopus, and Ovid databases. Article
      selection proceeded according to the search strategy on the basis of the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Only
      studies that compared laparoscopic and percutaneous kidney cryoablation were
      included in the meta-analysis. Eleven retrospective comparative studies were
      identified and selected for the analysis, including 1725 cases: 804 (46.6%)
      percutaneous and 921 (53.4%) laparoscopic cryoablations. Percutaneous
      cryoablation was performed more frequently for posterior tumors (P < .001),
      whereas laparoscopy was more common for endophytic lesions (P = .01). The length
      of follow-up was longer for laparoscopy (P < .001). Percutaneous cryoablation was
      associated with a significantly shorter hospital stay (P < .001). A lower
      likelihood of residual disease was recorded for laparoscopic (P = .003), whereas
      tumor recurrence rate favored percutaneous cryoablation (P = .02). The 2
      procedures were similar for recurrence-free survival (P = .08), and overall
      survival (P = .51). No significant difference was found in postoperative
      estimated glomerular filtration rate (P = .78). Laparoscopic and percutaneous
      kidney cryoablation offer similar favorable oncological outcomes with minimal
      effect on renal function. The percutaneous access can offer shorter hospital stay
      and faster recovery, which can be appealing in an era of cost restraint.

PMID- 28442228
TI  - Debating the Role of Arousal in Delirium Diagnosis: Should Delirium Diagnosis Be
      Inclusive or Restrictive?
AB  - Delirium is common in acute, postacute, and long-term care settings, and it can
      be difficult to recognize, especially without deliberate mental status
      evaluation. Because delirium typically presents with altered arousal and arousal
      can be assessed within a matter of seconds, routine assessment of arousal offers
      an efficient means of delirium screening. Nevertheless, impaired arousal often
      precludes formal assessment of attention and awareness, the cardinal features of
      delirium per the current Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition. Here we debate the relative merits of "ruling in" as delirious
      noncomatose patients with impaired arousal (inclusive approach) vs reserving
      delirium diagnosis to patients in whom diagnostic criteria can be elicited
      (restrictive approach). Inclusivism provides efficiency and may prevent missing
      or delaying delirium diagnosis. The restrictive approach challenges the utility
      of ruling such patients in as delirious and advocates for identifying mental
      states that directly inform clinical care. Both positions, however, firmly
      emphasize the value of routine clinical assessment of arousal.

PMID- 28442229
TI  - Changing attitudes to childhood immunisation in English parents.
AB  - OBJECTIVES: We undertook a national survey of parental attitudes to childhood
      vaccinations and compared results with those in earlier comparable surveys
      covering a 10year period. METHODS: We randomly selected 275 nationally
      representative sampling locations in England. Interviewers identified eligible
      primary care givers (referred to as parents) of children aged from 2months to
      <5years and conducted home-based interviews between January and April 2015. We
      aimed to recruit 1000 parents of children aged 0-2years and 1000 of children aged
      3-4years. The questionnaire covered all aspects of the immunisation process,
      vaccines administered in pregnancy and from infancy to pre-school with a maximum
      of 86 mixed questions. RESULTS: Interviews were completed with 1792 parents of
      whom 1130 had children aged 0-2years and 999 had children aged 3-4years; 337 had
      children of both ages. The findings showed that confidence in and acceptance of
      the vaccination programme was high. Only 2% of parents reported refusing
      vaccination whilst 90% reported vaccinating their children automatically when
      due. Almost all parents (97%) had access to the internet and 34% consulted web
      based resources for information on vaccination. Parents who used chat rooms or
      discussion forums for this purpose were significantly more likely to say they had
      seen something that would make them doubt having their child(ren) immunised (31%
      compared to 8% amongst all parents). Health professionals and the NHS were seen
      as the most trusted source of advice on immunisation (90% agreed/strongly agreed
      with each). Very few parents did not trust these sources (4% and 3% disagreed,
      respectively). CONCLUSIONS: Health professionals remain extremely important in
      communicating information about vaccination and are highly trusted by parents; a
      trust that has increased in recent years. Despite most parents seeking
      information on the Internet, trust in and advice from health care professionals
      appeared to be key factors influencing parental decisions.

PMID- 28442230
TI  - Case-control vaccine effectiveness studies: Data collection, analysis and
      reporting results.
AB  - The case-control methodology is frequently used to evaluate vaccine effectiveness
      post-licensure. The results of such studies provide important insight into the
      level of protection afforded by vaccines in a 'real world' context, and are
      commonly used to guide vaccine policy decisions. However, the potential for bias
      and confounding are important limitations to this method, and the results of a
      poorly conducted or incorrectly interpreted case-control study can mislead
      policies. In 2012, a group of experts met to review recent experience with case
      control studies evaluating vaccine effectiveness; we summarize the
      recommendations of that group regarding best practices for data collection,
      analysis, and presentation of the results of case-control vaccine effectiveness
      studies. Vaccination status is the primary exposure of interest, but can be
      challenging to assess accurately and with minimal bias. Investigators should
      understand factors associated with vaccination as well as the availability of
      documented vaccination status in the study context; case-control studies may not
      be a valid method for evaluating vaccine effectiveness in settings where many
      children lack a documented immunization history. To avoid bias, it is essential
      to use the same methods and effort gathering vaccination data from cases and
      controls. Variables that may confound the association between illness and
      vaccination are also important to capture as completely as possible, and where
      relevant, adjust for in the analysis according to the analytic plan. In
      presenting results from case-control vaccine effectiveness studies, investigators
      should describe enrollment among eligible cases and controls as well as the
      proportion with no documented vaccine history. Emphasis should be placed on
      confidence intervals, rather than point estimates, of vaccine effectiveness. Case
      control studies are a useful approach for evaluating vaccine effectiveness;
      however careful attention must be paid to the collection, analysis and
      presentation of the data in order to best inform evidence-based vaccine policies.

PMID- 28442231
TI  - Case-control vaccine effectiveness studies: Preparation, design, and enrollment
      of cases and controls.
AB  - Case-control studies are commonly used to evaluate effectiveness of licensed
      vaccines after deployment in public health programs. Such studies can provide
      policy-relevant data on vaccine performance under 'real world' conditions,
      contributing to the evidence base to support and sustain introduction of new
      vaccines. However, case-control studies do not measure the impact of vaccine
      introduction on disease at a population level, and are subject to bias and
      confounding, which may lead to inaccurate results that can misinform policy
      decisions. In 2012, a group of experts met to review recent experience with case
      control studies evaluating the effectiveness of several vaccines; here we
      summarize the recommendations of that group regarding best practices for
      planning, design and enrollment of cases and controls. Rigorous planning and
      preparation should focus on understanding the study context including healthcare
      seeking and vaccination practices. Case-control vaccine effectiveness studies are
      best carried out soon after vaccine introduction because high coverage creates
      strong potential for confounding. Endpoints specific to the vaccine target are
      preferable to non-specific clinical syndromes since the proportion of non
      specific outcomes preventable through vaccination may vary over time and place,
      leading to potentially confusing results. Controls should be representative of
      the source population from which cases arise, and are generally recruited from
      the community or health facilities where cases are enrolled. Matching of controls
      to cases for potential confounding factors is commonly used, although should be
      reserved for a limited number of key variables believed to be linked to both
      vaccination and disease. Case-control vaccine effectiveness studies can provide
      information useful to guide policy decisions and vaccine development, however
      rigorous preparation and design is essential.

PMID- 28442232
TI  - A genetic risk score predicts cardiovascular events in patients with stable
      coronary artery disease.
AB  - BACKGROUND: Genetic risk scores (GRSs) may predict cardiovascular risk in
      community-based populations. However, studies investigating the association with
      recurrent cardiovascular events in patients with established coronary artery
      disease (CAD) are conflicting. METHODS: We genotyped 879 patients with high-risk
      stable CAD and created a GRS based on 45 single nucleotide polymorphisms
      previously reported to be associated with CAD in genome-wide association studies.
      Patients were categorised into high or low GRS according to the median GRS and
      followed for recurrent cardiovascular events using national Danish registries.
      The primary endpoint was a composite of myocardial infarction, coronary
      revascularisation, and cardiovascular death. RESULTS: Median (interquartile
      range) follow-up time was 2.8 (2.4-3.8)years. The cumulative incidence
      proportions of the primary endpoint at 1 and 3years were 6.4% and 11.5% in high
      GRS patients vs. 2.5% and 7.3% in low-GRS patients. The corresponding relative
      risks were 2.56 (95% confidence interval (CI) 1.29-5.07), and 1.57 (95% CI 1.02
      2.44). The adjusted hazard ratio (HR) of the primary endpoint was 1.50 (95% CI
      1.00-2.25). The most pronounced effect of a high GRS was observed on coronary
      revascularisations (adjusted HR 2.10 [95% CI 1.08-4.07]). Risks of cardiovascular
      death (adjusted HR 1.07 [95% CI 0.46-2.48]) and all-cause death (adjusted HR 1.15
      [95% CI 0.65-2.03]) were unaffected. CONCLUSIONS: A GRS predicts recurrent
      cardiovascular events in high-risk stable CAD patients. The observed effect was
      mainly driven by coronary revascularisations.

PMID- 28442233
TI  - The CHADS2 and CHA2DS2-VASc scores predict atrial fibrillation in dyslipidemic
      individuals: Role of incorporating low high-density lipoprotein cholesterol
      levels.
AB  - AIM: To investigate the value of CHADS2 and CHA2DS2-VASc scores in predicting
      atrial fibrillation (AF) among dyslipidemic individuals and assess the additional
      value of incorporating low levels of high-density lipoprotein cholesterol (HDL
      C). METHODS: This observational study included 1241 individuals attending a lipid
      clinic. Models including clinical and laboratory parameters were constructed to
      test the predictive value of CHADS2 and CHA2DS2-VASc scores as well as low HDL-C
      levels for incident AF. Low HDL-C levels were defined as <40 and <50mg/dL for
      male and female subjects, respectively. RESULTS: After excluding 18 patients with
      AF at baseline, 1223 subjects were followed-up for a median period of 6years
      (IQR: 4-10), and 34 (2.8%) developed AF. Baseline CHADS2 (OR: 1.71; 95% CI: 1.28
      2.29, p<0.001) and CHA2DS2-VASc scores (OR: 1.56; 95% CI: 1.26-1.92, p<0.001) as
      well as low HDL-C levels (OR: 3.79; 95% CI: 1.85-7.75, p<0.001) were
      significantly associated with new-onset AF. ROC curve analyses showed that both
      CHADS2 and CHA2DS2-VASc scores were significant predictors for new-onset AF (C
      Statistic: CHADS2 0.679, p<0.001; CHA2DS2-VASc 0.698, p<0.001). Higher CHADS2
      scores were associated with reduced event-free survival from AF (log-rank=10.62,
      p=0.001) with differences potentiated if stratified by CHA2DS2-VASc score (log
      rank=22.29, p<0.001). After incorporating low HDL-C levels, both scores achieved
      slightly higher C-Statistic for AF prediction (0.690 and 0.707, respectively,
      p<0.001). CONCLUSIONS: CHADS2 and CHA2DS2-VASc scores predict new AF in
      dyslipidemic patients. Risk prediction improved modestly when low HDL-C levels
      were included.

PMID- 28442234
TI  - Impact of restrictive lung disorder on cardiovascular mortality in a general
      population: The Yamagata (Takahata) study.
AB  - BACKGROUND: Obstructive lung disorder (OLD) is known to be associated with
      cardiovascular disease. However, the impact of restrictive lung disorder (RLD) on
      cardiovascular mortality has not been fully investigated in the apparently
      healthy general population. OBJECTIVES: To clarify whether RLD is associated with
      cardiovascular mortality in the general population. METHODS AND RESULTS: This
      community-based cohort study included 3247 subjects who participated in an annual
      health check in Takahata. We performed spirometry in registered subjects and
      found that 194 (6%) had RLD, 262 (8%) had OLD, and 73 (2%) had RLD and OLD
      (Mixed). During a 10-year follow-up, there were 210 deaths, including 57
      cardiovascular deaths. Cardiovascular mortality of subjects with RLD was
      significantly higher than that of subjects with normal lung function. Although
      the subjects with RLD were younger, comprised fewer smokers, and were more likely
      to be female than those with OLD, cardiovascular mortality of subjects with RLD
      was comparable to that of subjects with OLD. Subjects with RLD had a higher
      prevalence of atrial fibrillation (AF) than those with OLD, and the prevalence of
      AF was increased with advanced severity of RLD. Multivariate Cox proportional
      hazard analysis revealed that RLD was an independent predictor of cardiovascular
      death (hazard ratio 2.61, 95% confidence interval, 1.22-5.21) after adjustment
      for confounders, but OLD was not. The net reclassification improvement and
      integrated discrimination improvement were significantly increased by the
      addition of RLD to conventional cardiovascular risk factors. CONCLUSION: The
      presence of RLD was associated with cardiovascular mortality in the general
      population.

PMID- 28442235
TI  - Reply-Letter to the Editor-Glutamine dipeptide-supplemented parenteral nutrition
      improves the clinical outcomes of critically ill patients: A systematic
      evaluation of randomised controlled trials.

PMID- 28442237
TI  - Long-term ERT monitoring of biogeochemical changes of an aged hydrocarbon
      contamination.
AB  - Adequate management of contaminated sites requires information with improved
      spatio-temporal resolution, in particular to assess bio-geochemical processes,
      such as the transformation and degradation of contaminants, precipitation of
      minerals or changes in groundwater geochemistry occurring during and after
      remediation procedures. Electrical Resistivity Tomography (ERT), a geophysical
      method sensitive to pore-fluid and pore-geometry properties, permits to gain
      quasi-continuous information about subsurface properties in real-time and has
      been consequently widely used for the characterization of hydrocarbon-impacted
      sediments. However, its application for the long-term monitoring of processes
      accompanying natural or engineered bioremediation is still difficult due to the
      poor understanding of the role that biogeochemical processes play in the
      electrical signatures. For in-situ studies, the task is further complicated by
      the variable signal-to-noise ratio and the variations of environmental parameters
      leading to resolution changes in the electrical images. In this work, we present
      ERT imaging results for data collected over a period of two years on a site
      affected by a diesel fuel contamination and undergoing bioremediation. We report
      low electrical resistivity anomalies in areas associated to the highest
      contaminant concentrations likely due transformations of the contaminant due to
      microbial activity and accompanying release of metabolic products. We also report
      large seasonal variations of the bulk electrical resistivity in the contaminated
      areas in correlation with temperature and groundwater level fluctuations.
      However, the amplitude of bulk electrical resistivity variations largely exceeds
      the amplitude expected given existing petrophysical models. Our results suggest
      that the variations in electrical properties are mainly controlled by microbial
      activity which in turn depends on soil temperature and hydrogeological
      conditions. Therefore, ERT can be suggested as a promising tool to track
      microbial activity during bioremediation even though further research is still
      needed to completely understand the bio-geochemical processes involved and their
      impact on electrical signatures.

PMID- 28442238
TI  - The influence of small-scale interlayer heterogeneity on DDT removal efficiency
      for flushing technology.
AB  - With an aim to investigate the influence of small-scale interlayer heterogeneity
      on DDT removal efficiency, batch test including surfactant-stabilized foam
      flushing and solution flushing were carried out. Two man-made heterogeneous
      patterns consisting of coarse and fine quartz sand were designed to reveal the
      influencing mechanism. Moreover, the removal mechanism and the corresponding
      contribution by foam flushing were quantitatively studied. Compared with
      surfactant solution flushing, the DDT removal efficiency by surfactant-stabilized
      foam flushing increased by 9.47% and 11.28% under heterogeneous patterns 1 and 2,
      respectively. The DDT removal contributions of improving sweep efficiency for
      heterogeneous patterns 1 and 2 by foam flushing were 40.82% and 45.98%, and the
      contribution of dissolving capacity were 59.18% and 54.02%, respectively. The
      dissolving capacity of DDT played a major role in DDT removal efficiency by foam
      flushing under laboratory conditions. And the DDT removal contribution of
      significant improving sweep efficiency was higher than that of removal decline
      caused by weak solubilizing ability of foam film compared with solution flushing.
      The obtained results indicated that the difference of DDT removal efficiency by
      foam flushing was decreased under two different heterogeneous patterns with the
      increase of the contribution of improving foam flushing sweep efficiency. It
      suggested that foam flushing can reduce the disturbance from interlayer
      heterogeneity in remediating DDT contaminated heterogeneous medium.

PMID- 28442236
TI  - Red blood cell membrane omega-3 fatty acid levels and physical performance: Cross
      sectional data from the MAPT study.
AB  - BACKGROUND & AIMS: Studies have shown that omega-3 polyunsaturated fatty acids
      (PUFAs) are associated with brain, cardiovascular and immune function, as well as
      physical performance and bone health in older adults. So far, few studies have
      highlighted the associations between PUFA status and performance-based tests of
      physical function. To study the associations between the omega-3 index (red blood
      cell (RBC) membrane content of omega-3 PUFAs, such as eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA)) and physical performance measured with the Short
      Physical Performance Battery (SPPB) in a sample of community-dwelling older
      adults. DESIGN: Cross-sectional study using the baseline data of the Multidomain
      Alzheimer's Disease Trial (MAPT), a randomized, placebo-controlled trial.
      PARTICIPANTS AND MEASUREMENTS: 1449 participants with available data on PUFAs
      were included. Omega-3 index and Short Physical Performance Battery (SPPB) scores
      were measured at enrollment and the omega-3 index expressed as the percentage of
      total fatty acid content was calculated. We also dichotomized the omega-3 index
      as low (lowest quartile) vs. high (three upper quartiles). RESULTS: Participants
      were 75.2 (+/-4.4) years old, 64.5% were female. Bivariate analyses found that
      participants who were in the lowest omega-3 index quartile (Q1) had a SPPB score
      significantly lower than participants in the three other quartiles (Q2-Q4).
      However, adjusted (for age, gender, cognitive function, depressive status, Body
      Mass Index and grip strength) multiple linear regression showed that the omega-3
      index-SPPB score association did not reach statistical significance [beta = 
      0.166; (-0.346; 0.013); p = 0.07] in our sample. CONCLUSION: This cross-sectional
      study found that participants with a low omega-3 index had worse performance
      based test results of physical function than people with a high omega-3 index,
      but this association did not reach statistical significance once confounders were
      controlled for. Studies looking at the over-time associations between PUFA status
      and physical performance changes may shed more light on this topic.

PMID- 28442239
TI  - Roadmap to control HBV and HDV epidemics in China.
AB  - PURPOSE: Hepatitis B virus (HBV) is endemic in China. Almost 10% of HBV infected
      individuals are also infected with hepatitis D virus (HDV) which has a 5-10 times
      higher mortality rate than HBV mono-infection. The aim of this manuscript is to
      devise strategies that can not only control HBV infections but also HDV
      infections in China under the current health care budget in an optimal manner.
      METHODS: Using a mathematical model, an annual budget of $10billion was optimally
      allocated among five interventions namely, testing and HBV adult vaccination,
      treatment for mono-infected and dually-infected individuals, second line
      treatment for HBV mono-infections, and awareness programs. RESULTS: We determine
      that the optimal strategy is to test and treat both infections as early as
      possible while applying awareness programs at full intensity. Under this
      strategy, an additional 19.8million HBV, 1.9million HDV infections and
      0.25million lives will be saved over the next 10years at a cost-savings of
      $79billion than performing no intervention. Introduction of second line treatment
      does not add a significant economic burden yet prevents 1.4million new HBV
      infections and 15,000 new HDV infections. CONCLUSION: Test and treatment programs
      are highly efficient in reducing HBV and HDV prevalence in the population. Under
      the current health budget in China, not only test and treat programs but
      awareness programs and second line treatment can also be implemented that
      minimizes prevalence and mortality, and maximizes economic benefits.

PMID- 28442240
TI  - Cercopithifilaria bainae in Rhipicephalus sanguineus sensu lato ticks from dogs
      in Brazil.
AB  - Rhipicephalus sanguineus sensu lato (s.l.) ticks act as intermediate host for a
      range of canine vector-borne pathogens, including nematodes ranked in the genus
      Cercopithifilaria. Though being the object of several studies in the last years,
      information on the distribution of these parasites is still lacking. In this
      study, the occurrence of Cercopithifilaria spp. was investigated in on-host
      population of R. sanguineus s.l. collected from naturally infested dogs. Ticks
      (n=1906, including one larva, 294 nymphs and 1611 adults) were sampled on
      domestic dogs (n=155) living in the municipality of Garanhuns (northeastern
      Brazil). Tick collections (n=36) were performed every 8 days, from October 2015
      to June 2016. Filarioid larvae detected at tick dissection were morphologically
      and morphometrically identified at species level. At the end of the study, only
      R. sanguineus s.l. ticks were collected, with the highest number in January 2016
      (n=254) and the lowest in June 2016 (n=26). Out of 1906 dissected ticks, 2.68%
      (51/1906) harboured Cercopithifilaria bainae larvae, whose identification was
      molecularly confirmed, with a nucleotide identity of 99% with C. bainae. Data
      here reported indicate that, in the study area, R. sanguineus s.l. is the
      predominant tick infesting domestic dogs. Accordingly, these animals are at a
      high risk of C. bainae infection.

PMID- 28442241
TI  - Molecular detection and phylogenetic analysis of severe fever with
      thrombocytopenia syndrome virus in shelter dogs and cats in the Republic of
      Korea.
AB  - Severe fever with thrombocytopenia syndrome is a tick-borne infectious disease.
      The present study investigated the prevalence of severe fever with
      thrombocytopenia syndrome virus (SFTSV) in shelter dogs and cats in the Republic
      of Korea (ROK). Blood samples were collected from 426 dogs and 215 cats in animal
      shelters throughout the ROK in 2016. Of the tested samples, one (0.2%) dog and
      one (0.5%) cat were positive for SFTSV. Phylogenetic analysis of the sequences
      obtained in the present study showed that the viruses belonged to the J3 clade,
      which is considered the dominant clade in the ROK. This study reports the first
      molecular detection of SFTSV in shelter dogs and cats in the ROK.

PMID- 28442242
TI  - Dosimetric analysis of liver toxicity after liver metastasis stereotactic body
      radiation therapy.
AB  - PURPOSE: The aim of this study is to describe the incidence and type of liver
      toxicity seen following liver metastases stereotactic body radiation therapy
      (SBRT) and the corresponding clinical and dosimetric factors associated with
      toxicity. METHODS AND MATERIALS: Between 2002 and 2009, 81 evaluable patients
      with liver metastases were treated on 2 prospective studies assessing SBRT, with
      prescription doses based on the effective liver volume irradiated evaluated.
      Toxicity was defined as grade >=2 classic or nonclassic radiation induced liver
      disease (RILD). Specific toxicity endpoints evaluated were worsening
      transaminases and albumin levels within 3 months of SBRT. RESULTS: Seventy
      percent of patients had colorectal carcinoma, 55% had extrahepatic disease, 1
      patient had hepatitis B, and 54% had received prior chemotherapy. Baseline
      transaminases were elevated at Common Terminology Criteria for Adverse Effects,
      V4.0, grade 1, 2, and 3 levels in 33 (41%), 2 (2%), and 0 (0%) patients. The mean
      prescription dose was 43 Gy (27.7-60 Gy) in 6 fractions. The mean liver (minus
      gross tumor volume) dose (MLD) was 16 Gy (3-25.6 Gy) in 6 fractions. No classic
      or nonclassical >=grade 2 RILD was observed. Within 3 months of SBRT, 49 (61%)
      patients had worsening of grade of transaminase and 23 (28%) patients had a
      reduction in albumin, all transient (majority grade <=2 toxicity) without
      subsequent clinical toxicity. Seventeen patients exceeded Quantitative Analysis
      of Normal Tissue Effects in the Clinic MLD guidelines (<=20 Gy), 13 (76%) of whom
      had worsening of transaminase grade. On multivariate analysis, worsening of liver
      enzymes was more likely in patients with higher doses to the spared 700 mL of
      liver (P = .026), and reduction of albumin was more likely with higher effective
      liver volume (odds ratio, 1.53 [range, 1.08-2.16]) P = .016). CONCLUSIONS: Liver
      metastases SBRT is safe with a low risk of transient biochemical liver toxicity,
      more likely in patients with a higher effective liver volume and higher doses to
      the spared uninvolved liver volume.

PMID- 28442243
TI  - Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse
      hippocampus.
AB  - The regulation of neural precursor cells (NPCs) is indispensable for a properly
      functioning brain. Abnormalities in NPC proliferation, differentiation, survival,
      or integration have been linked to various neurological diseases including
      Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal
      Fragile X mouse hippocampus despite the importance of this developmental time
      point, which marks the highest expression level of FMRP, the protein missing in
      Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated
      to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study,
      we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice
      (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression
      and decreased Ki67 expression, which collectively indicated aberrant NPC biology.
      Intriguingly, flow cytometric analysis of the expression of the antigens CD15,
      CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem
      cells (GLAST+CD15+CD133+) and an increased proportion of neuroblasts (PSA
      NCAM+CD15+) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression
      levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9
      hippocampus, as well as a decreased proportion of cells in the G2/M phases of the
      P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding
      with a decrease in neural stem cells and an increase in neuroblasts. Together,
      these results show the importance of FMRP in the developing hippocampal formation
      and suggest abnormalities in cell cycle regulation in Fragile X.

PMID- 28442244
TI  - Automatic high-resolution infarct detection using volumetric multiphase dual
      energy CT.
AB  - OBJECTIVES: Late contrast enhancement CT (LCE-CT) visualizes the presence of
      myocardial infarcts. Differentiation of the contrast-enhanced infarct from blood
      pool is challenging. We developed a novel method using data from first pass CT
      angiography (CTA) imaging to enable automatic infarct detection. MATERIALS AND
      METHODS: A canine model of myocardial infarction was produced in 11 animals. Two
      months later, first pass CTA (90 kVp) and LCE-CT (dual energy 90 kVp/150 kVp tin
      filtered) were performed. Late gadolinium enhancement MRI was used as reference
      standard. The CTA and LCE-CT were co-registered using a fully automatic non-rigid
      method based on curved B-splines. The method allowed for limited elastic
      deformation and the considerable differences in attenuation between first-pass
      and delayed image. The blood pool was easily identified on the CTA image by high
      attenuation. Because CTA and LCE-CT were registered, the blood pool segmentation
      can be directly transferred to the LCE-CT - thereby solving the key problem of
      infarct/blood pool differentiation. The remaining segmentation of infarcted vs.
      noninfarcted myocardium was performed using a threshold. Automatic and MRI-guided
      expert segmentations of LCE-CT infarcts were compared to each other on volume and
      area basis (intraclass correlation coefficient, ICC) and on voxel basis (dice
      similarity coefficient, DSC between automatic and expert CT segmentation). CT
      infarct volumes were compared with the reference standard MRI. RESULTS: The
      infarcts were mainly subendocardial (81%) and relatively small (median MRI
      infarct mass 7.4 g). The automatic segmentation showed excellent agreement with
      expert segmentation on volume and area measurements (ICC = 0.96 and 0.87,
      respectively). DSC showed moderately good agreement (DSC = 0.47). Compared to MRI
      there was modest agreement (ICC = 0.62) and excellent correlation (R = 0.9).
      Manual interaction was less than 1 min per exam. CONCLUSION: We propose an
      automatic method for infarct segmentation on LCE-CT using multiphase CT
      information, which showed excellent agreement with expert readers and favorable
      correlation with MRI.

PMID- 28442245
TI  - Changes in apolipoprotein E-containing high-density lipoprotein (HDL) have little
      impact on HDL-cholesterol measurements using homogeneous assays in normolipidemic
      and dyslipidemic subjects.
AB  - BACKGROUND: High-density lipoprotein-cholesterol (HDL-C) is generally measured
      using several homogeneous assays. We aimed to clarify whether apolipoprotein E
      containing HDL (apoE-HDL) subfractions are altered during storage, and if so,
      whether such changes affect the HDL-C concentration measured using homogeneous
      assays. METHODS: We stored serum from normolipidemic (n=32) and dyslipidemic
      (n=17) subjects at 4 degrees C for up to 7days. ApoE-HDL subfractions were
      analyzed using native 2-dimensional gel (native 2D-gel) electrophoresis. HDL-C
      concentrations were determined using 2 precipitation and 4homogeneous assays.
      RESULTS: Native 2D-gel electrophoresis revealed variously sized apoE-HDL
      subfractions. After 4h incubation at 37 degrees C, subfractions of smaller
      particles were converted into larger particles by lecithin:cholesterol
      acyltransferase (LCAT) activity. After 7days storage at 4 degrees C, the smaller
      subfractions were decreased in the normolipidemic group, accompanying increases
      in larger subfractions, whereas changes in the respective subfractions varied
      among individuals in the dyslipidemic group. HDL-C concentrations were
      significantly lower after storage at 4 degrees C in all assays, except that using
      Sekisui Medical's reagent. Therefore, changes in HDL-C concentration and apoE-HDL
      subfractions were independent of each other. CONCLUSION: ApoE-HDL subfractions
      change during storage, but these changes are not linked to those in HDL-C
      concentration measured using homogeneous assays.

PMID- 28442246
TI  - Prognostic impact of nutritional risk assessment in patients with chronic
      schizophrenia.
AB  - Protein-energy wasting is associated with poor outcome in various clinical
      settings. However, the prevalence of malnutrition and the prognostic impact of
      nutritional status are poorly understood in institutionalized patients with
      chronic schizophrenia. This study aimed to assess the predictive ability of the
      Geriatric Nutritional Risk Index and Onodera's Prognostic Nutritional Index for
      long-term outcomes in patients with chronic schizophrenia. All measurements,
      including nutritional scores, were performed at baseline after the enrollment of
      542 (64.6% men, mean age 53.8+/-9.7years) patients with chronic schizophrenia.
      The median follow-up period was 408days. The endpoints were falls and infection
      related hospitalizations. At study completion, 34 patients suffered falls and 40
      patients were admitted to hospitals due to infection. Both indices showed
      significant association with infectious complications, whereas only the Onodera's
      Prognostic Nutritional Index was significantly associated with falls. The
      adjusted hazard ratios (95% confidence intervals) of low Onodera's Prognostic
      Nutritional Index were 2.38 (1.16-4.86) for falls and 1.99 (1.05-3.76) for
      infectious complications. The Onodera's Prognostic Nutritional Index is more
      appropriate than the Geriatric Nutritional Risk Index in identifying patients
      with chronic schizophrenia who are at risk for malnutrition and nutrition-related
      morbidity. Further studies are needed to explore whether early detection of
      patients with schizophrenia who are at risk for malnutrition could lead to the
      reduction of morbidity and mortality with the aid of appropriate interventions.

PMID- 28442248
TI  - Social environments and interpersonal distance regulation in psychosis: A virtual
      reality study.
AB  - BACKGROUND: Experimentally studying the influence of social environments on
      mental health and behavior is challenging, as social context is difficult to
      standardize in laboratory settings. Virtual Reality (VR) enables studying social
      interaction in terms of interpersonal distance in a more ecologically valid
      manner. Regulation of interpersonal distance may be abnormal in patients with
      psychotic disorders and influenced by environmental stress, symptoms or distress.
      AIMS: To investigate interpersonal distance in people with a psychotic disorder
      and at ultrahigh risk for psychosis (UHR) compared to siblings and controls in
      virtual social environments, and explore the relationship between clinical
      characteristics and interpersonal distance. METHODS: Nineteen UHR patients, 52
      patients with psychotic disorders, 40 siblings of patients with a psychotic
      disorder and 47 controls were exposed to virtual cafes. In five virtual cafe
      visits, participants were exposed to different levels of social stress, in terms
      of crowdedness, ethnicity and hostility. Measures on interpersonal distance,
      distress and state paranoia were obtained. Baseline measures included trait
      paranoia, social anxiety, depressive, positive and negative symptoms. RESULTS:
      Interpersonal distance increased when social stressors were present in the
      environment. No difference in interpersonal distance regulation was found between
      the groups. Social anxiety and distress were positively associated with
      interpersonal distance in the total sample. CONCLUSION: This VR paradigm
      indicates that interpersonal distance regulation in response to environmental
      social stressors is unaltered in people with psychosis or UHR. Environmental
      stress, social anxiety and distress trigger both people with and without
      psychosis to maintain larger interpersonal distances in social situations.

PMID- 28442247
TI  - Regional enrichment analyses on genetic profiles for schizophrenia and bipolar
      disorder.
AB  - Both schizophrenia (SZ) and bipolar disorder (BD) are highly heritable
      psychiatric disorders. The significant genomic risk loci are of great importance
      but with no guarantee of known functional impact and they cannot totally explain
      the genetic inheritance. In this study we present regional enrichment analyses
      across the genome, aiming to strike a balance between individual risk loci and
      integrated regional effects. Chromosomes were partitioned into 2 million base
      pair regions (indicated by an underscore sign in the cytogenetic bands) on which
      enrichment tests are performed. In the discovery phase, we leverage the
      Psychiatric Genomics Consortium SZ and BD initial association test results for
      European Ancestry (EA) population and dbGAP SNP data for African Ancestry (AA)
      population. 78 and 48 regions show significantly enriched associations with SZ
      and BD respectively in the EA population, and nine are in common including MHC,
      3p21.1, 7p22.3_2, 2q32.3_2, 8q24.3_4, and 19q13.33_1. The most unique SZ
      associated region is 1p21.3_3, while the most unique BD associated region is
      6q25.2_1. For the AA population fewer regions are discovered with only 10%
      overlapping with that of EA population. A replication test using Wellcome Trust
      Case Control Consortium data for EA population verified 9% of the SZ enriched
      regions and 40% of the BD enriched regions. In summary, we showed that regional
      enrichment analyses produce reliable genetic association profiles using about one
      tenth of samples compared to single base-pair genome wide association approach.
      The identified association regions will be useful for further genetic functional
      studies.

PMID- 28442249
TI  - The relationship between cognitive insight and cognitive performance among
      individuals with at-risk mental state for developing psychosis.
AB  - Impairments in cognitive insight-the capacity to appraise and modify one's own
      distorted beliefs-are believed to be associated with the formation of psychosis.
      Nevertheless, the association between cognitive insight and cognitive function
      among people with at-risk mental state (ARMS) for developing psychotic illness
      has not been made clear. In this study, we used the Beck Cognitive Insight Scale
      (BCIS) to assess cognitive insight and the Brief Assessment of Cognition in
      Schizophrenia (BACS) and the Wisconsin Card Sorting Test (WCST) to assess
      cognitive functions. Fifty subjects with ARMS and 29 healthy volunteers were
      recruited as participants. The scores for the two groups on the BCIS, BACS, and
      WCST were compared and Spearman's rank correlations between the domains of the
      BCIS and cognitive performance were examined in each group. No significant
      differences were found in BCIS scores between these groups, whereas all of the
      cognitive function scores were poorer in the participants with ARMS. In the ARMS
      group, higher self-certainty on the BCIS was significantly correlated with lower
      performance in the mean number of categories achieved (rho=-0.31, P=0.03) and
      perseverative errors of the Nelson type (rho=0.29, P=0.04) on the WCST. This
      indicates that excessively high self-certainty might be linked with weaknesses in
      cognitive flexibility or set-shifting ability in people with ARMS.

PMID- 28442250
TI  - Analysis of microbiota in first episode psychosis identifies preliminary
      associations with symptom severity and treatment response.
AB  - The effects of gut microbiota on the central nervous system, along its possible
      role in mental disorders, have received increasing attention. Here we
      investigated differences in fecal microbiota between 28 patients with first
      episode psychosis (FEP) and 16 healthy matched controls and explored whether such
      differences were associated with response after up to 12months of treatment.
      Numbers of Lactobacillus group bacteria were elevated in FEP-patients and
      significantly correlated with severity along different symptom domains. A
      subgroup of FEP patients with the strongest microbiota differences also showed
      poorer response after up to 12months of treatment. The present findings support
      the involvement of microbiota alterations in psychotic illness and may provide
      the basis for exploring the benefit of their modulation on treatment response and
      remission.

PMID- 28442252
TI  - Approaches towards the development of chimeric DPP4/ACE inhibitors for treating
      metabolic syndrome.
AB  - Designing drug candidates exhibiting polypharmacology is one of the strategies
      adopted by medicinal chemists to address multifactorial diseases. Metabolic
      disease is one such multifactorial disorder characterized by hyperglycaemia,
      hypertension and dyslipidaemia among others. In this paper we report a new class
      of molecular framework combining the pharmacophoric features of DPP4 inhibitors
      with those of ACE inhibitors to afford potent dual inhibitors of DPP4 and ACE.

PMID- 28442251
TI  - Liquidus Tracking: Large scale preservation of encapsulated 3-D cell cultures
      using a vitrification machine.
AB  - Currently, cryo-banking of multicellular structures such as organoids, especially
      in large volumes at clinical scale >1 L, remains elusive for reasons such as
      insufficient dehydration and cryoprotectant additive (CPA1) penetration, slow
      cooling and warming rates and devitrification processes. Here we introduce the
      concept of Liquidus Tracking (LT) using a semi-automated process for liquid
      volumes of up to 450 ml including 130 ml of alginate encapsulated liver cells
      (AELC) that archived controlled and reversible vitrification with minimized
      toxicity. First a CPA solution with optimal properties for LT was developed by
      employing different small scale test systems. Combining sugars such as glucose
      and raffinose with Me2SO improved post-exposure (at +0.5  degrees C) viabilities
      from 6% +/-3.6 for Me2SO alone up to 58% +/-6.1 and 65% +/-14.2 respectively (p <
      0.01). Other permeating CPAs (e.g. ethylene glycol, propylene glycol, methanol)
      were investigated as partial replacements for Me2SO. A mixture of Me2SO, ethylene
      glycol and glucose (ratio 4:2:1- termed LTdeg) supported glass-forming tendencies
      with appropriate low viscosities and toxicities required for LT. When running the
      full LT process, using Me2SO alone, no viable cells were recovered; using LTdeg,
      viable recoveries were improved to 40% +/-8 (p<0.001%). Further refinements of
      improved mixing technique further improved recovery after LT. Recoveries of
      specific liver cell functions such as synthesis of albumin and alpha-fetoprotein
      (AFP) were retained in post thaw cultures. In summary: By developing a low
      toxicity CPA solution of low viscosity (LTdeg) suitable for LT and by improving
      the stirring system, post-warming viability of AELC of up to 90% and a AFP
      secretion of 89% were reached. Results show that it may be possible to develop LT
      as a suitable cryogenic preservation process for different cell therapy products
      at large scale.

PMID- 28442253
TI  - Optimization of M4 positive allosteric modulators (PAMs): The discovery of
      VU0476406, a non-human primate in vivo tool compound for translational
      pharmacology.
AB  - This letter describes the further chemical optimization of the 5-amino-thieno[2,3
      c]pyridazine series (VU0467154/VU0467485) of M4 positive allosteric modulators
      (PAMs), developed via iterative parallel synthesis, culminating in the discovery
      of the non-human primate (NHP) in vivo tool compound, VU0476406 (8p). VU0476406
      is an important in vivo tool compound to enable translation of pharmacodynamics
      from rodent to NHP, and while data related to a Parkinson's disease model has
      been reported with 8p, this is the first disclosure of the optimization and
      discovery of VU0476406, as well as detailed pharmacology and DMPK properties.

PMID- 28442254
TI  - Copalic acid analogs down-regulate androgen receptor and inhibit small chaperone
      protein.
AB  - Copalic acid, one of the diterpenoid acids in copaiba oil, inhibited the
      chaperone function of alpha-crystallin and heat shock protein 27kD (HSP27). It
      also showed potent activity in decreasing an HSP27 client protein, androgen
      receptor (AR), which makes it useful in prostate cancer treatment or prevention.
      To develop potent drug candidates to decrease the AR level in prostate cancer
      cells, more copalic acid analogs were synthesized. Using the level of AR as the
      readout, 15 of the copalic acid analogs were screened and two compounds were much
      more potent than copalic acid. The compounds also dose-dependently inhibited AR
      positive prostate cancer cell growth. Furthermore, they inhibited the chaperone
      activity of alpha-crystallin as well.

PMID- 28442255
TI  - Acetanilide and bromoacetyl-lysine derivatives as activators for human histone
      deacetylase 8.
AB  - In the current study, seven compounds (i.e. 1-7) were found to be novel
      activators for the Nepsilon-acetyl-lysine deacetylation reaction catalyzed by
      human histone deacetylase 8 (HDAC8). When assessed with the commercially
      available HDAC8 peptide substrate Fluor-de-Lys(r)-HDAC8 that harbors the
      unnatural 7-amino-4-methylcoumarin (AMC) residue immediately C-terminal to the
      Nepsilon-acetyl-lysine residue to be deacetylated, our compounds exhibited
      comparable activation potency to that of TM-2-51, the strongest HDAC8 activator
      reported in the current literature. However, when assessed with an AMC-less
      peptide substrate derived from the native HDAC8 non-histone substrate protein
      Zinc finger protein ZNF318, while our compounds were all found to be able to
      activate HDAC8 deacetylation reaction, TM-2-51 was found not to be able to. Our
      compounds also seemed to be largely selective for HDAC8 over other classical
      HDACs. Moreover, treatment with the strongest activator among our compounds (i.e.
      7) was found to decrease the KM of the above AMC-less HDAC8 substrate, while
      nearly maintaining the kcat of the HDAC8-catalyzed deacetylation on this
      substrate.

PMID- 28442256
TI  - Functional evaluation of synthetic flavonoids and chalcones for potential
      antiviral and anticancer properties.
AB  - Flavonoids, stilbenes, and chalcones are plant secondary metabolites that often
      possess diverse biological activities including anti-inflammatory, anti-cancer,
      and anti-viral activities. The wide range of bioactivities poses a challenge to
      identify their targets. Here, we studied a set of synthetically generated
      flavonoids and chalcones to evaluate for their biological activity, and compared
      similarly substituted flavonoids and chalcones. Substituted chalcones, but not
      flavonoids, showed inhibition of viral translation without significantly
      affecting viral replication in cells infected with hepatitis C virus (HCV). We
      suggest that the chalcones used in this study inhibit mammalian target of
      rapamycin (mTOR) pathway by ablating phosphorylation of ribosomal protein 6
      (rps6), and also the kinase necessary for phosphorylating rps6 in Huh7.5 cells
      (pS6K1). In addition, selected chalcones showed inhibition of growth in Ishikawa,
      MCF7, and MDA-MB-231 cells resulting an IC50 of 1-6ug/mL. When similarly
      substituted flavonoids were used against the same set of cancer cells, we did not
      observe any inhibitory effect. Together, we report that chalcones show potential
      for anti-viral and anti-cancer activities compared to similarly substituted
      flavonoids.

PMID- 28442258
TI  - [Author's reply].

PMID- 28442257
TI  - Cocaine use is associated with a higher prevalence of elevated ST2
      concentrations.
AB  - BACKGROUND: Cocaine is a well-known risk factor for acute cardiac events, but the
      effects in users outside of acute events are less clear. We investigated a
      possible association between cocaine use and the concentration of a novel
      biomarker for cardiac stress and heart failure, ST2. METHODS: A case-control
      study was conducted to compare ST2 concentrations by the presence of cocaine in
      patients presenting for care, but not cardiac care, at an urban safety net
      hospital. RESULTS: In samples taken from 100 cocaine-positive and 100 cocaine
      negative patients, the presence of cocaine was associated with ST2
      concentrations>35ng/mL. Serum concentrations of benzoylecgonine, a major cocaine
      metabolite, were significantly correlated with ST2 concentrations. CONCLUSIONS:
      Cocaine use is associated with subclinical cardiac stress and damage outside of
      acute cardiac events. This information could add to better stratification of
      cocaine users with elevated ST2 concentrations who may be at higher risk for
      developing heart failure and other cardiac complications.

PMID- 28442259
TI  - Microbial community structure and diversity in a municipal solid waste landfill.
AB  - Municipal solid waste (MSW) landfills are the most prevalent waste disposal
      method and constitute one of the largest sources of anthropogenic methane
      emissions in the world. Microbial activities in disposed waste play a crucial
      role in greenhouse gas emissions; however, only a few studies have examined
      metagenomic microbial profiles in landfills. Here, the MiSeq high-throughput
      sequencing method was applied for the first time to examine microbial diversity
      of the cover soil and stored waste located at different depths (0-150cm) in a
      typical MSW landfill in Yangzhou City, East China. The abundance of
      microorganisms in the cover soil (0-30cm) was the lowest among all samples,
      whereas that in stored waste decreased from the top to the middle layer (30-90cm)
      and then increased from the middle to the bottom layer (90-150cm). In total, 14
      phyla and 18 genera were found in the landfill. A microbial diversity analysis
      showed that Firmicutes, Proteobacteria, and Bacteroidetes were the dominant
      phyla, whereas Halanaerobium, Methylohalobius, Syntrophomonas, Fastidiosipila,
      and Spirochaeta were the dominant genera. Methylohalobius (methanotrophs) was
      more abundant in the cover layers of soil than in stored waste, whereas
      Syntrophomonas and Fastidiosipila, which affect methane production, were more
      abundant in the middle to bottom layers (90-150cm) in stored waste. A canonical
      correlation analysis showed that microbial diversity in the landfill was most
      strongly correlated with the conductivity, organic matter, and moisture content
      of the stored waste.

PMID- 28442260
TI  - Synthesis of benzoxazole derivatives as interleukin-6 antagonists.
AB  - A growing number of studies have demonstrated that interleukin (IL)-6 plays
      pathological roles in the development of chronic inflammatory disease and
      autoimmune disease by activating innate immune cells and by stimulating adaptive
      inflammatory T cells. So, suppression of IL-6 function may be beneficial for
      prevention and treatment of chronic inflammatory disease. This study reports that
      a series of synthetic derivatives of benzoxazole have suppressive effects on IL-6
      mediated signaling. Among 16 synthetic derivatives of benzoxazole, the compounds
      4, 6, 11, 15, 17, and 19 showed a strong suppressive activity against IL-6
      induced phosphorylation of signal transducer and activator of transcription
      (STAT) 3 by 80-90%. While the cell viability was strongly decreased by compounds
      11, 17, 19, the compounds 4, 6, and 15 revealed less cytotoxicity. We then
      examined the effects of the compounds on inflammatory cytokine production by CD4+
      T cells. CD4+ T cells were induced to differentiate into interferon (IFN)-gamma-,
      IL-17-, or IL-4-producing effector T cells in the presence of either the compound
      4 or the compound 7. While the inactive compound 7 had no significant effect on
      the cytokine production by effector T cells, the active compound 4 strongly
      suppressed the production of inflammatory cytokines IFN-gamma and IL-17, and also
      inhibited allergic inflammatory cytokines IL-4, IL-5, and IL-13 produced by
      effector Th2 cells. These results suggest that a benzoxazole derivative, compound
      4 effectively suppresses IL-6-STAT3 signaling and inflammatory cytokine
      production by T cells and provides a beneficial effect for treating chronic
      inflammatory and autoimmune disease.

PMID- 28442261
TI  - Identification of a novel fluoropyrrole derivative as a potassium-competitive
      acid blocker with long duration of action.
AB  - With the aim to find a novel long-lasting potassium-competitive acid blocker (P
      CAB) that would perfectly overcome the limitations of proton pump inhibitors
      (PPIs), we tried various approaches based on pyrrole derivative 1b as a lead
      compound. As part of a comprehensive approach to identification of a new drug, we
      explored excellent compounds that have low lipophilicity by introducing a polar
      hetero-aromatic group at position 5 of the pyrrole ring. Among the compounds
      synthesized, fluoropyrrole derivative 37c, which has a 2-F-3-Py group at the
      fifth position, lower pKa, and much lower ClogP and logD values than 1b dose,
      showed potent gastric-acid suppressive action resulting from gastric H+,K+-ATPase
      inhibition in animal models. Its maximum intragastric pH elevation effect was
      strong in rats, and its duration of action was much longer than that of either
      lansoprazole or lead compound 1b in dogs. Therefore, compound 37c can be
      considered a promising new P-CAB with long duration of action.

PMID- 28442263
TI  - Minor mental disorders and work conditions.

PMID- 28442262
TI  - An integrated chemical biology approach reveals the mechanism of action of HIV
      replication inhibitors.
AB  - Continuous flow (microfluidic) chemistry was employed to prepare a small focused
      library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have
      been reported to exhibit activity against the human immunodeficiency virus (HIV),
      but their molecular target had not been identified. We tested the initial set of
      DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of
      the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization
      of 1i led to the identification of HIV replication inhibitors such as 1l with
      cellular potency comparable with the clinical drug nevirapine (NVP). Mechanism of
      action (MOA) studies using cellular and biochemical assays coupled with 3D
      fingerprinting and in silico modeling demonstrated that these drug-like probe
      compounds exert their effects by inhibiting the viral reverse transcriptase
      polymerase (RT). This led to the design and synthesis of the novel DHPM 1at that
      inhibits the replication of drug resistant strains of HIV. Our work demonstrates
      that combining flow chemistry-driven analogue refinement with phenotypic assays,
      in silico modeling and MOA studies is a highly effective strategy for hit-to-lead
      optimization applicable to the discovery of future therapeutic agents.

PMID- 28442265
TI  - Downregulation of beta-arrestin 1 suppresses glioblastoma cell malignant
      progression vis inhibition of Src signaling.
AB  - Glioblastoma multiforme (GBM) is one of the most common brain malignancies
      worldwide and is typically associated with a dismal prognosis, yet the mechanisms
      underlying its aggressiveness remain unclear. Here, we revealed that beta
      arrestin 1 was overexpressed in GBM and contributed to poorer outcome. Knockdown
      of beta-arrestin 1 suppressed the proliferation, invasiveness and glycolysis of
      GBM cells, and also enhanced temozolomide efficacy. Further, we discovered that
      knockdown of beta-arrestin 1 decreased the activity of Src, and suppression of
      Src signaling was critically involved in beta-arrestin 1 silencing-mediated
      suppression of GBM malignancies. Finally, we investigated the effect of beta
      arrestin 1 knockdown on the tumor growth and survival of xenograft models, and
      found that shbeta-arrestin 1 apparently inhibited GBM growth in vivo and resulted
      in better survival of mice. Taken together, our findings suggest that knockdown
      of beta-arrestin 1 can suppress GBM cell proliferation, invasion and glycolysis
      by inhibiting Src signaling. Thus, targeting beta-arrestin 1 may be a potential
      therapeutic strategy for GBM treatment.

PMID- 28442266
TI  - CLN5 is cleaved by members of the SPP/SPPL family to produce a mature soluble
      protein.
AB  - The Neuronal ceroid lipofuscinoses (NCLs) are a group of recessive disorders of
      childhood with overlapping symptoms including vision loss, ataxia, cognitive
      regression and premature death. 14 different genes have been linked to NCLs (CLN1
      CLN14), but the functions of the proteins encoded by the majority of these genes
      have not been fully elucidated. Mutations in the CLN5 gene are responsible for
      the Finnish variant late-infantile form of NCL (Finnish vLINCL). CLN5 is
      translated as a 407 amino acid transmembrane domain containing protein that is
      heavily glycosylated, and subsequently cleaved into a mature soluble protein.
      Functionally, CLN5 is implicated in the recruitment of the retromer complex to
      endosomes, which is required to sort the lysosomal sorting receptors from
      endosomes to the trans-Golgi network. The mechanism that processes CLN5 into a
      mature soluble protein is currently not known. Herein, we demonstrate that CLN5
      is initially translated as a type II transmembrane protein and subsequently
      cleaved by SPPL3, a member of the SPP/SPPL intramembrane protease family, into a
      mature soluble protein consisting of residues 93-407. The remaining N-terminal
      fragment is then cleaved by SPPL3 and SPPL2b and degraded in the proteasome. This
      work further characterizes the biology of CLN5 in the hopes of identifying a
      novel therapeutic strategy for affected children.

PMID- 28442264
TI  - Mitochondrial LON protease-dependent degradation of cytochrome c oxidase subunits
      under hypoxia and myocardial ischemia.
AB  - The mitochondrial ATP dependent matrix protease, Lon, is involved in the
      maintenance of mitochondrial DNA nucleoids and degradation of abnormal or
      misfolded proteins. The Lon protease regulates mitochondrial Tfam (mitochondrial
      transcription factor A) level and thus modulates mitochondrial DNA (mtDNA)
      content. We have previously shown that hypoxic stress induces the PKA-dependent
      phosphorylation of cytochrome c oxidase (CcO) subunits I, IVi1, and Vb and a time
      dependent reduction of these subunits in RAW 264.7 murine macrophages subjected
      to hypoxia and rabbit hearts subjected to ischemia/reperfusion. Here, we show
      that Lon is involved in the preferential turnover of phosphorylated CcO subunits
      under hypoxic/ischemic stress. Induction of Lon protease occurs at 6 to 12 h of
      hypoxia and this increase coincides with lower CcO subunit contents. Over
      expression of flag-tagged wild type and phosphorylation site mutant Vb and IVi1
      subunits (S40A and T52A, respectively) caused marked degradation of wild type
      protein under hypoxia while the mutant proteins were relatively resistant.
      Furthermore, the recombinant purified Lon protease degraded the phosphorylated
      IVi1 and Vb subunits, while the phosphorylation-site mutant proteins were
      resistant to degradation. 3D structural modeling shows that the phosphorylation
      sites are exposed to the matrix compartment, accessible to matrix PKA and Lon
      protease. Hypoxic stress did not alter CcO subunit levels in Lon depleted cells,
      confirming its role in CcO turnover. Our results therefore suggest that Lon
      preferentially degrades the phosphorylated subunits of CcO and plays a role in
      the regulation of CcO activity in hypoxia and ischemia/reperfusion injury.

PMID- 28442267
TI  - Shell alterations in limpets as putative biomarkers for multi-impacted coastal
      areas.
AB  - During the last years, shell alterations in gastropods have been proposed as
      tools to be used in monitoring programs. However, no studies were so far
      performed investigating the relationships among shell parameters and classical
      biomarkers of damage. The relationship between shell alterations (biometrics,
      shape and elemental composition) and biomarkers (LPO and DNA strand break) was
      evaluated in the limpet L. subrugosa sampled along a contamination gradient in a
      multi-impacted coastal zone from southeastern Brazil. Statistically significant
      differences were detected among sites under different pollution levels. The
      occurrence of shell malformations was consistent with environmental levels of
      several hazardous substances reported for the studied area and related to lipid
      peroxidation and DNA damage. In addition, considering the low mobility, wide
      geographic distribution, ease of collection and abundance of limpets in coastal
      zones, this putative tool may be a cost-effective alternative to traditional
      biomarkers. Thus, shell alterations in limpets seem to be good proxies for
      assessing biological adverse effects in multi-impacted coastal zones.

PMID- 28442268
TI  - Generalized palisaded neutrophilic and granulomatous dermatitis-a cutaneous
      manifestation of chronic myelomonocytic leukemia? A clinical, histopathological,
      and molecular study of 3 cases.
AB  - Palisaded neutrophilic and granulomatous dermatitis (PNGD) is characterized by
      erythematous papules or plaques on trunk or limbs and is frequently associated
      with rheumatologic, autoimmune, or hematologic malignancies. Histopathology shows
      interstitial granulomas composed of epitheloid histiocytes in the reticular
      dermis with surrounding foci of collagen degeneration and variable neutrophilic
      inflammation. We report 3 cases of generalized PNGD associated with chronic
      myelomonocytic leukemia (CMML), a myelodysplastic/myeloproliferative neoplasm,
      which may show a variety of cutaneous manifestations. SRSF2 P95 hotspot
      mutations, found in 40%-50% of CMML cases, were retrospectively detected in skin
      and bone marrow biopsies of all 3 patients, in 1 of them already 5 years before
      CMML diagnosis. Generalized PNGD may represent a type of cutaneous manifestation
      of CMML. Because diagnosis of CMML is frequently difficult in cases with isolated
      persistent monocytosis and minimal dysplasia in the bone marrow, patients with a
      generalized PNGD should be evaluated for the presence of hematologic disorders
      including CMML, ideally supported by mutational analyses.

PMID- 28442269
TI  - Enhanced adhesion and in situ photothermal ablation of cancer cells in surface
      functionalized electrospun microfiber scaffold with graphene oxide.
AB  - The physicochemical characteristics of a biomaterial surface highly affect the
      interaction with living cells. Recently, much attention has been focused on the
      adhesion properties of functional biomaterials toward cancer cells, since is
      expected to control metastatic spread of a tumor, which is related to good
      probability containing the progression of disease burden. Here, we designed an
      implantable poly(caprolactone)-based electrospun microfiber scaffold, henceforth
      PCLMF-GO, to simultaneously capture and kill cancer cells by tuning
      physicochemical features of the hybrid surface through nitrogen plasma activation
      and hetero-phase graphene oxide (GO) covalent functionalization. The surface
      immobilization of GO implies enhanced cell adhesion and proliferation, promoting
      the selective adhesion of cancer cells, even if allowing cancer associated
      fibroblast (CAFs) capture. We also display that the functionalization with GO,
      thanks to the high near-infrared (NIR) absorbance, enables the discrete
      photothermal eradication of the captured cancer cells in situ (~98%).

PMID- 28442270
TI  - Interpretation of physiological indicators of motivation: Caveats and
      recommendations.
AB  - Motivation scientists employing physiological measures to gather information
      about motivation-related states are at risk of committing two fundamental errors:
      overstating the inferences that can be drawn from their physiological measures
      and circular reasoning. We critically discuss two complementary approaches,
      Cacioppo and colleagues' model of psychophysiological relations and construct
      validation theory, to highlight the conditions under which these errors are
      committed and provide guidance on how to avoid them. In particular, we
      demonstrate that the direct inference from changes in a physiological measure to
      changes in a motivation-related state requires the demonstration that the measure
      is not related to other relevant psychological states. We also point out that
      circular reasoning can be avoided by separating the definition of the motivation
      related state from the hypotheses that are empirically tested.

PMID- 28442271
TI  - Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture
      collected and finger-stick capillary whole-blood samples: a cohort study.
AB  - BACKGROUND: Point-of-care hepatitis C virus (HCV) RNA testing offers an advantage
      over antibody testing (which only indicates previous exposure), enabling
      diagnosis of active infection in a single visit. In this study, we evaluated the
      performance of the Xpert HCV Viral Load assay with venepuncture and finger-stick
      capillary whole-blood samples. METHODS: Plasma and finger-stick capillary whole
      blood samples were collected from participants in an observational cohort
      enrolled at five sites in Australia (three drug and alcohol clinics, one
      homelessness service, and one needle and syringe programme). We compared the
      sensitivity and specificity of the Xpert HCV Viral Load test for HCV RNA
      detection by venepuncture and finger-stick collection with the Abbott RealTime
      HCV Viral Load assay (gold standard). FINDINGS: Of 210 participants enrolled
      between Feb 8, 2016, and July 27, 2016, 150 participants had viral load testing
      results for the three assays tested. HCV RNA was detected in 45 (30% [95% CI 23
      38]) of 150 participants based on Abbott RealTime. Sensitivity of the Xpert HCV
      Viral Load assay for HCV RNA detection in plasma collected by venepuncture was
      100.0% (95% CI 92.0-100.0) and specificity was 99.1% (95% CI 94.9-100.0).
      Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in samples
      collected by finger-stick was 95.5% (95% CI 84.5-99.4) and specificity was 98.1%
      (95% CI 93.4-99.8). No adverse events caused by the index test or the reference
      standard were observed. IMPLICATIONS: The Xpert HCV Viral Load test can detect
      active infection from a finger-stick sample, which represents an advance over
      antibody-based tests that only indicate past or previous exposure. FUNDING:
      National Health and Medical Research Council (Australia), Cepheid, South Eastern
      Sydney Local Health District (Australia), and Merck Sharp & Dohme (Australia).

PMID- 28442272
TI  - Rapid HCV RNA testing: removing the final obstacle to elimination.

PMID- 28442274
TI  - Sex differences in exercise efficacy to improve cognition: A systematic review
      and meta-analysis of randomized controlled trials in older humans.
AB  - Exercise is a non-pharmacological strategy to mitigate the deleterious effects of
      aging on brain health. However, a large amount of variation exists in its
      efficacy. Sex of participants and exercise type are two possible factors
      contributing to this variation. To better understand this, we conducted a
      concurrent systematic review and meta-analysis of cognitively healthy older
      adults. Executive functions, episodic memory, visuospatial function, word
      fluency, processing speed and global cognitive function were examined for
      exercise- and sex-dependent effects. For executive functions, three types of
      exercise interventions - aerobic training, resistance training, and multimodal
      training (i.e., both aerobic and resistance training) - were associated with
      larger effect sizes in studies comprised of a higher percentage of women compared
      to studies with a lower percentage of women. This suggests that women's executive
      processes may benefit more from exercise than men. Regardless of sex, compared to
      control, all three exercise training approaches enhanced visuospatial function,
      but only multimodal training enhanced episodic memory. Overall, aerobic training
      led to greater benefits than resistance training in global cognitive function and
      executive functions, while multimodal combined training led to greater benefits
      than aerobic training for global cognitive function, episodic memory, and word
      fluency. Possible underlying mechanisms, including brain-derived neurotrophic
      factor and sex steroid hormones, are discussed.

PMID- 28442275
TI  - Wellbeing perception and the impact on external training output among elite
      soccer players.
AB  - OBJECTIVES: The objective of the investigation was to observe the impact of
      player wellbeing on the training output of elite soccer players. DESIGN:
      Prospective cohort design. METHODS: Forty-eight soccer players (age: 25.3+/
      3.1years; height: 183+/-7cm; mass: 72+/-7kg) were involved in this single season
      observational study across two teams. Each morning, pre-training, players
      completed customised perceived wellbeing questionnaires. Global positioning
      technology devices were used to measure external load (total distance, total high
      speed running distance, high speed running, player load, player load slow,
      maximal velocity, maximal velocity exposures). Players reported ratings of
      perceived exertion using the modified Borg CR-10 scale. Integrated training load
      ratios were also analysed for total distance:RPE, total high speed distance:RPE
      player load:RPE and player load slow:RPE respectively. RESULTS: Mixed-effect
      linear models revealed significant effects of wellbeing Z-score on external and
      integrated training load measures. A wellbeing Z-score of -1 corresponded to a 
      18+/-2m (-3.5+/-1.1%), 4+/-1m (-4.9+/-2.1%,) 0.9+/-0.1kmh-1 (-3.1+/-2.1%), 1+/-1
      (-4.6+/-2.9%), 25+/-3AU (-4.9+/-3.1%) and 11+/-0.5AU (-8.9+/-2.9%) reduction in
      total high speed distance, high speed distance, maximal velocity, maximal
      velocity exposures, player load and player load slow respectively. A reduction in
      wellbeing impacted external:internal training load ratios and resulted in -0.49+/
      0.12mmin-1, -1.20+/-0.08mmin-1,-0.02+/-0.01AUmin-1 in total distance:RPE, total
      high speed distance:RPE and player load slow:RPE respectively. CONCLUSIONS: The
      results suggest that systematic monitoring of player wellbeing within soccer
      cohorts can provide coaches with information about the training output that can
      be expected from individual players during a training session.

PMID- 28442276
TI  - Investigating the effects of nitrous oxide sedation on frontal-parietal
      interactions.
AB  - Although functional connectivity has received considerable attention in the study
      of consciousness, few studies have investigated functional connectivity limited
      to the sedated state where consciousness is maintained but impaired. The aim of
      the present study was to investigate changes in functional connectivity of the
      parietal-frontal network resulting from nitrous oxide-induced sedation, and to
      determine the neural correlates of cognitive impairment during consciousness
      transition states. Electroencephalography was acquired from healthy adult
      patients who underwent nitrous oxide inhalation to induce cognitive impairment,
      and was analyzed using Granger causality (GC). Periods of awake, sedation and
      recovery for GC between frontal and parietal areas in the delta, theta, alpha,
      beta, gamma and total frequency bands were obtained. The Friedman test with post
      hoc analysis was conducted for GC values of each period for comparison. As a
      sedated state was induced by nitrous oxide inhalation, power in the low frequency
      band showed increased activity in frontal regions that was reversed with
      discontinuation of nitrous oxide. Feedback and feedforward connections analyzed
      in spectral GC were changed differently in accordance with EEG frequency bands in
      the sedated state by nitrous oxide administration. Calculated spectral GC of the
      theta, alpha, and beta frequency regions in the parietal-to-frontal direction was
      significantly decreased in the sedated state while spectral GC in the reverse
      direction did not show significant change. Frontal-parietal functional
      connectivity is significantly affected by nitrous oxide inhalation. Significantly
      decreased parietal-to-frontal interaction may induce a sedated state.

PMID- 28442273
TI  - The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic
      steatohepatitis.
AB  - Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is marked
      by the presence of macrosteatosis on liver histology but is often clinically
      asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is
      a more severe form of liver disease characterized by inflammation and fibrosis.
      Further progression leads to cirrhosis, which predisposes patients to
      hepatocellular carcinoma or liver failure. The mechanism by which simple
      steatosis progresses to steatohepatitis is not entirely clear. However, multiple
      pathways have been proposed. A common link amongst many of these pathways is
      disruption of the homeostasis of bile acids. Other than aiding in the absorption
      of lipids and lipid-soluble vitamins, bile acids act as ligands. For example,
      they bind to farnesoid X receptor, which is critically involved in many of the
      pathways responsible for maintaining bile acid, glucose, and lipid homeostasis.
      Alterations to these pathways can lead to dysregulation of energy balance and
      increased inflammation and fibrosis. Repeated insults over time may be the key to
      development of steatohepatitis. For this reason, current drug therapies target
      aspects of these pathways to try to reduce and halt inflammation and fibrosis.
      This review will focus on the role of bile acids in these various pathways and
      how changes in these pathways may result in steatohepatitis. While there is no
      approved pharmaceutical treatment for either hepatic steatosis or
      steatohepatitis, this review will also touch upon the multitude of potential
      therapies.

PMID- 28442277
TI  - Prostate brachytherapy, either alone or in combination with external beam
      radiation, is associated with longer overall survival in men with favorable
      pathologic Group 4 (Gleason score 8) prostate cancer.
AB  - PURPOSE: Conventional prostate cancer risk stratification results in considerable
      heterogeneity within each prognostic group. Men with pathologic grade Group 4
      (Gleason score 8) but otherwise low-risk features have been identified as a
      favorable subset of high-risk prostate cancer. Given recent randomized data
      supporting improved cancer outcome with brachytherapy in intermediate- and high
      risk prostate cancer, we sought to evaluate brachytherapy utilization and overall
      survival (OS) for these patients. METHODS AND MATERIALS: We queried the National
      Cancer Database for clinical T1c-T2a N0 M0 prostate cancer with prostate-specific
      antigen <10 ng/mL and Gleason score 8 adenocarcinoma on biopsy. All patients
      received androgen deprivation therapy and either external beam radiation therapy
      (EBRT) alone, brachytherapy alone, or a combination of EBRT with brachytherapy
      boost (brachytherapy + EBRT). Kaplan-Meier OS estimates as well as univariate and
      multivariate Cox proportional hazards regression analyses were performed.
      Propensity score-matched analyses were performed to further control for baseline
      confounders. RESULTS: Four thousand four hundred ninety-six patients were
      identified with a median followup of 62.5 months (range, 2.3-119.8). Median age
      was 72 years (range, 41-90+). Utilization of brachytherapy decreased from 2004 to
      2009. The odds ratio for brachytherapy by year (continuous variable) was 0.86 (p
      < 0.001). Five-year OS was 84%, 88%, and 89% for the EBRT alone, brachytherapy
      alone, and brachytherapy + EBRT groups, respectively. On multivariate analysis,
      higher median income, low comorbidity score, and treatment with brachytherapy
      alone (hazard ratio, 0.66; p = 0.005) or brachytherapy + EBRT (hazard ratio,
      0.70; p = 0.001) remained associated with longer OS. Propensity score matching
      confirmed longer OS associated with either brachytherapy regimen. CONCLUSIONS: Of
      those men with World Health Organization pathologic grade Group 4 (Gleason score
      8) prostate cancer and otherwise favorable prognostic features treated with
      androgen deprivation therapy and radiation therapy, longer OS was achieved when
      prostate brachytherapy was included, whether used alone or in combination with
      supplemental EBRT. In spite of these excellent outcomes, prostate brachytherapy
      utilization is declining in the United States.

PMID- 28442278
TI  - Feasibility and normal values of an integrated conductivity (NanoductTM) sweat
      test system in healthy newborns.
AB  - BACKGROUND: NanoductTM is a simple and practical sweat analysis system measuring
      conductivity in situ. It requires only three microlitres of sweat, making it
      especially applicable to newborns. METHODS: We measured conductivity in 260
      healthy term infants at the age of four days, and again at four weeks to
      determine the proportion of successful tests, test duration, and normal values
      for sweat conductivity in newborns. RESULTS: Sufficient sweat was collected in
      159/260 of four-day olds (61%), and in 225/239 of four-week olds (94%). Mean (sd)
      test duration was 27 (5) and 25 (5) min. Mean (sd, range) conductivity was
      53mmol/l (16, 8-114) at age four days, and 36 (9, 12-64) at four weeks.
      CONCLUSIONS: Determination of sweat conductivity using NanoductTM cannot be
      recommended for four-day old newborns. However, at the age of four weeks the
      success rate is high (94%), and conductivity values at that age are comparable to
      older healthy children.

PMID- 28442279
TI  - Avoiding Catastrophic Forgetting.
AB  - Humans regularly perform new learning without losing memory for previous
      information, but neural network models suffer from the phenomenon of catastrophic
      forgetting in which new learning impairs prior function. A recent article
      presents an algorithm that spares learning at synapses important for previously
      learned function, reducing catastrophic forgetting.

PMID- 28442280
TI  - Kidney disease in patients with obesity: It is not always obesity-related
      glomerulopathy alone.
AB  - OBJECTIVE: Patients with obesity are at risk for chronic kidney disease. The aim
      is to characterize the spectrum of kidney disease in these patients, which may be
      related to obesity, termed obesity-related glomerulopathy (ORG), or may have
      other diseases secondary to associated or unassociated medical conditions.
      METHODS: Native kidney biopsies from 2000 to 2012 were retrospectively reviewed
      from all patients with body mass index >30kg/m2. Glomerular diameter was measured
      using a standard micrometer and clinicopathologic characteristics were analyzed.
      RESULTS: 4% (287) of all biopsies were obtained from patients with obesity (mean:
      weight 122kg, BMI 40.4+/-7.35kg/m2) for proteinuria in 93% and renal
      insufficiency in 53%. Frequent associated factors were abnormal glucose
      metabolism (31%), hypertension (60%), and obstructive sleep apnea (9%). Typical
      lesions of ORG were seen in 41% of cases and additional diseases in the rest.
      Glomerulomegaly, glomerular diameter >180MUm, was present in 84% of cases (mean
      224MUm) vs normal size in 11% (mean 157MUm), but was not increased with higher
      magnitude of obesity. Proteinuria was highest in patients with idiopathic FSGS
      (mean 8g/24h) and immune complex diseases (mean 7.4g/24h) and was mainly
      subnephrotic in obesity-related FSGS and tubulo-interstitial diseases. Creatinine
      levels were highest in tubulointerstitial diseases (mean 8.4mg/dL) and
      progressive diabetic nephropathy (mean 2.5mg/dL). CONCLUSIONS: Diverse kidney
      pathology superimposed on ORG is present in patients with obesity with varied
      clinical renal disease, some of which may be amenable for therapy. Kidney biopsy
      will assist in delineating these lesions for appropriate management and
      prognosis.

PMID- 28442281
TI  - Determinants of Knowledge and Attitudes Regarding Pain among Nurses in a
      University Hospital: A Cross-sectional Study.
AB  - The aim of this cross-sectional study was to evaluate the primary determinants of
      knowledge and attitudes regarding pain among nurses in a hospital setting. All
      registered nurses employed at participating units at a university hospital were
      invited to participate. Information on work experience, education, and hospital
      unit was evaluated using a questionnaire. The Knowledge and Attitude Survey
      Regarding Pain instrument was used to assess knowledge on pain management. The
      difference in knowledge between nurses with different levels of education was
      assessed with analysis of variance. The discriminatory ability of each question
      was determined with item response theory, and the association between correct
      answers to individual items and the total score were calculated using linear
      regression. Participants were 235 nurses, 51% of the 459 invited. The overall
      pain knowledge score was 26.1 (standard deviation 5.3, range 8-38) out of a total
      of 40 possible. Those with an advanced degree in nursing scored on average 2.9
      points higher than those who did not have an advance degree (95% confidence
      interval: 0.9-4.7). Responses to clinical vignette questions showed more
      difference between nurses with different levels of knowledge of pain management
      than the other questions. Participants with the correct response to the best
      discriminatory item had 5.35 (95% confidence interval 4.08-6.61) points higher
      total score than those with an incorrect answer. Higher education is associated
      with better knowledge on pain management. To assess pain knowledge, the ability
      to interpret and solve a clinical vignette leads to better results than answering
      direct questions.

PMID- 28442282
TI  - Attitude and Intention Regarding Pain Management among Chinese Nursing Students:
      A Cross-Sectional Questionnaire Survey.
AB  - Optimal pain management is a priority in effective nursing care. Lack of
      sufficient pain knowledge associated with inadequate pain management has been
      proved. However, the intention, defined as the predictor of behavior, regarding
      pain management remains unknown. Therefore, the study was to determine the
      attitude and intention regarding pain management among Chinese nursing students
      and investigate the underlying determinants and their interactions in terms of
      intention toward pain management. The Pain Management Survey Questionnaire,
      comprising the key determinants of the theory of planned behavior-that is, direct
      attitude, belief-based intention, subjective norm, direct control, and indirect
      control-was used to collect data from 512 nursing students who undertook clinical
      rotation in an affiliated hospital of a medical college in China. Data were
      analyzed using descriptive statistics, independent sample t test, Pearson
      correlation analysis, or structural equation modeling analysis. Chinese nursing
      students reported negative attitudes and behavioral intentions toward pain
      management. Direct control, subjective norm, belief-based attitude, and indirect
      control independently predicted nursing students' intention to treat patients
      with pain. Direct control was the strongest predictor. Structural equation
      modeling analysis further revealed 39.84% of the variance associated with
      intention that could be explained by determinants of the theory of planned
      behavior. Additionally, educational school level and previous pain management
      training had great effects on pain management intention. Overall, this study
      identified intention as an important factor in effective pain treatment. Chinese
      nursing students have negative attitudes and insufficient intention to pain
      management. Therefore, hospitals and universities in China should manage these
      factors to improve nursing students' practice regarding pain management.

PMID- 28442283
TI  - Development, Implementation, and Evaluation of Evidence-Based Cooking Videos for
      Cancer Survivors.

PMID- 28442284
TI  - Fitness Fatness Index and Alzheimer-specific mortality.
AB  - OBJECTIVE: We evaluated the specific association between a Fitness Fat Index
      (FFI) and Alzheimer's-specific mortality among a national sample of the broader
      U.S. adult population. METHODS: FFI was calculated as cardiorespiratory fitness
      (CRF) divided by waist-to-height ratio (WHR). Data from the 1999-2006 National
      Health and Nutrition Examination Survey (NHANES) were used to identify 16,146
      participants, ages 20-85. Data from participants in these cycles were linked to
      death certificate data from the National Death Index. Person-months of follow-up
      were calculated from the date of the interview until date of death or censoring
      on December 31, 2011, whichever came first. RESULTS: In a Cox proportional hazard
      model, for every 1 FFI unit increase, participants had a 14% reduced hazard of
      Alzheimer-specific death (HR=0.86; 95% CI: 0.83-0.90; P<0.001). When including
      diabetes and hypertension (via physician-diagnosis) as covariates, results were
      unchanged (HR=0.87; 95% CI: 0.82-0.91; P<0.001). Results were also unchanged when
      restricting the sample to those 50+years (HR=0.92; 95% CI: 0.88-0.97; P=0.005) or
      stratifying by men (HR=0.85; 95% CI: 0.81-0.91; P<0.001) or women (HR=0.86; 95%
      CI: 0.79-0.94; P=0.002). CONCLUSION: In this national sample of individuals at
      risk for Alzheimer's disease, increased FFI was associated with reduced risk of
      Alzheimer's-specific death. Thus, a more favorable fitness-to-fatness ratio is
      associated with reduced risk of Alzheimer's-specific mortality, underscoring the
      importance of fitness promoting and fatness reducing strategies.

PMID- 28442285
TI  - C-reactive protein, lipoprotein (a) and cystatin C levels increase with
      multimorbidity in older persons.

PMID- 28442286
TI  - Is abdominal auscultation a still relevant part of the physical examination?

PMID- 28442287
TI  - HLA-A, -B, -DRB1 allele and haplotype frequencies of 674 cord blood donors from
      North Italy.

PMID- 28442288
TI  - Expression and differential regulation of HLA-G isoforms in the retinal pigment
      epithelial cell line, ARPE-19.
AB  - The purpose of this study was to examine if HLA-G is expressed in the retinal
      pigment epithelium (RPE) cells of the eye. The RPE comprises the outer most layer
      of the retina and as such defines the interface to the blood and contributes to
      the immune privilege in the posterior part of the eye. One way the RPE might be
      regulating the immune system could be by expressing the non-classical human
      leukocyte antigen (HLA) molecule, HLA-G. We therefore sought to define if the RPE
      cell line, ARPE-19, expressed HLA-G and analyse the regulation as a response to
      pro-inflammatory cytokines. This was done by digital droplet PCR, measuring the
      gene expression of HLA-G in total RNA. The protein expression was analysed by
      immunohistochemistry and by immunofluorescence followed by confocal microscopy
      and the expression of the HLA-G isoforms was explored by fragment analysis. In
      the current study, we show that HLA-G is expressed by ARPE-19 cells and is
      upregulated as a response to pro-inflammatory cytokines. Moreover, we are the
      first to describe a differential regulation of the HLA-G isoforms as a direct
      response to stimulation. These results might indicate that HLA-G can be part of
      the immune privilege of the posterior part of the eye, but further experiments on
      primary RPE cells are needed.

PMID- 28442289
TI  - HLA-A, -B and -C allele and haplotype frequencies defined by next generation
      sequencing in a population of 519 English blood donors.
AB  - Whole gene next generation sequencing was used to determine the HLA class I
      haplotype and allele frequencies in a cohort of 519 English blood donors. This is
      the first report of HLA frequencies at third field resolution in a UK population
      with a total of 33, 52 and 30 alleles identified for HLA-A, -B and -C,
      respectively. Of the 1411 haplotypes determined, 281 had a frequency of greater
      than 0.05%. Data are available from the Allele Frequencies Net Database under the
      population name 'England Blood Donors of Mixed Ethnicity', identifier 3392.

PMID- 28442290
TI  - Large subcutaneous multi-xanthoma in familial hypercholesterolemia.

PMID- 28442291
TI  - The effect of group-based cardiac rehabilitation models on the quality of life
      and exercise capacity of patients with chronic heart failure.

PMID- 28442292
TI  - Effect of gender on the prognostic value of dobutamine stress myocardial contrast
      echocardiography.
AB  - BACKGROUND: Dobutamine stress contrast echo (DSCE) has a well-established
      prognostic value in the context of coronary artery disease (CAD). However, data
      regarding its prognostic capability separately in men and women are scarce. The
      aim of the current study was to assess gender-related differences in the
      prognostic performance of DSCE. METHODS: DSCE was performed in 2645 consecutive
      patients, who were classified into two groups depending on gender. Follow-up
      lasted 57.1+/-10.1 months. End points included all-cause mortality, cardiac
      death, late revascularization, and hospitalizations. Survival analysis was
      performed comparing men and women. RESULTS: Of the 2645 patients (59.3+/-8.7
      years), 69.1% were men. DSCE was positive in 23.4% of male patients, while in
      females, the respective percentage was 14.3%. There was statistically significant
      difference between the two groups with regard to end point occurrence (11.6% vs.
      6.1%, p<0.05). Multivariate analysis revealed that the DSCE response was the
      strongest predictor of adverse outcomes (Exp(B)=51.9, p<0.05) in both groups. The
      predictive model including DSCE results along with clinical data performed well
      without significant differences between males and females (C-index 0.93 vs. 0.87
      respectively, p=NS). CONCLUSION: DSCE has a strong prognostic value for patients
      with known or suspected CAD, regardless of patient gender. This makes DSCE an
      attractive screening option for women in whom CAD assessment can be challenging.

PMID- 28442294
TI  - Who benefits from antimicrobial combination therapy?

PMID- 28442293
TI  - Effect of appropriate combination therapy on mortality of patients with
      bloodstream infections due to carbapenemase-producing Enterobacteriaceae
      (INCREMENT): a retrospective cohort study.
AB  - BACKGROUND: The best available treatment against carbapenemase-producing
      Enterobacteriaceae (CPE) is unknown. The objective of this study was to
      investigate the effect of appropriate therapy and of appropriate combination
      therapy on mortality of patients with bloodstream infections (BSIs) due to CPE.
      METHODS: In this retrospective cohort study, we included patients with clinically
      significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited
      from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key
      data, death sooner than 24 h after the index date, therapy with an active
      antibiotic for at least 2 days when blood cultures were taken, and subsequent
      episodes in the same patient. We compared 30 day all-cause mortality between
      patients receiving appropriate (including an active drug against the blood
      isolate and started in the first 5 days after infection) or inappropriate
      therapy, and for patients receiving appropriate therapy, between those receiving
      active monotherapy (only one active drug) or combination therapy (more than one).
      We used a propensity score for receiving combination therapy and a validated
      mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox
      regression analyses. We stratified analyses of combination therapy according to
      INCREMENT-CPE mortality score (0-7 [low mortality score] vs 8-15 [high mortality
      score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490.
      FINDINGS: Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to
      CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this
      study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who
      received inappropriate therapy. The most frequent organism was Klebsiella
      pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate
      therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent
      carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]).
      Appropriate therapy was associated with lower mortality than was inappropriate
      therapy (132 [38.5%] of 343 patients died vs 57 [60.6%] of 94; absolute
      difference 22.1% [95% CI 11.0-33.3]; adjusted hazard ratio [HR] 0.45 [95% CI 0.33
      0.62]; p<0.0001). Among those receiving appropriate therapy, 135 (39%) received
      combination therapy and 208 (61%) received monotherapy. Overall mortality was not
      different between those receiving combination therapy or monotherapy (47 [35%] of
      135 vs 85 [41%] of 208; adjusted HR 1.63 [95% CI 0.67-3.91]; p=0.28). However,
      combination therapy was associated with lower mortality than was monotherapy in
      the high-mortality-score stratum (30 [48%] of 63 vs 64 [62%] of 103; adjusted HR
      0.56 [0.34-0.91]; p=0.02), but not in the low-mortality-score stratum (17 [24%]
      of 72 vs 21 [20%] of 105; adjusted odds ratio 1.21 [0.56-2.56]; p=0.62).
      INTERPRETATION: Appropriate therapy was associated with a protective effect on
      mortality among patients with BSIs due to CPE. Combination therapy was associated
      with improved survival only in patients with a high mortality score. Patients
      with BSIs due to CPE should receive active therapy as soon as they are diagnosed,
      and monotherapy should be considered for those in the low-mortality-score
      stratum. FUNDING: Spanish Network for Research in Infectious Diseases, European
      Development Regional Fund, Instituto de Salud Carlos III, and Innovative
      Medicines Initiative.

PMID- 28442295
TI  - The effects of repeated nitroglycerin administrations in rats; modeling migraine
      related endpoints and chronification.
AB  - BACKGROUND: Rodent models typically use a single nitroglycerin injection to
      induce migraine, yet migraine in clinical populations presents as recurrent
      episodes. Further, these models quantify behavioral endpoints that do not align
      with the clinical features of episodic migraine or migraine chronification and
      therefore may limit translational relevance. NEW METHOD: Rats received 5
      nitroglycerin (10mg/kg/2ml), propylene glycol/ethanol vehicle, or saline
      injections every third day over 15days. Behavioral endpoints were assessed 110min
      post nitroglycerin administration and included time spent light/dark chambers for
      photophobia as well as activity, facial pain expressions, and tactile allodynia.
      RESULTS: Animals administered nitroglycerin displayed photophobia, decreased
      activity, and increased facial pain expression. Similar alterations in
      photophobia and activity were seen in the vehicle treated animals, but these
      tended to diminish by the 4th or 5th injection. The presentation of spontaneous
      tactile allodynia was observed in the nitroglycerin group by the 5th episode.
      COMPARISON WITH EXISTING METHODS: Most NTG migraine models entail a single NTG
      administration and quantification of evoked allodynia. This paradigm employs
      recurring NTG episodes and clinically-relevant measures of photophobia,
      hypoactivity and facial grimace endpoints as well as introduces a novel arena
      apparatus to quantify spontaneous allodynia. CONCLUSIONS: This repeated NTG
      procedure and endpoint measures aligns with the frequency and clinical
      presentation of episodic migraine and its chronification, respectively. Further,
      propylene glycol ethanol vehicle contributes to migraine endpoints.

PMID- 28442296
TI  - An information theory framework for dynamic functional domain connectivity.
AB  - BACKGROUND: Dynamic functional network connectivity (dFNC) analyzes time
      evolution of coherent activity in the brain. In this technique dynamic changes
      are considered for the whole brain. This paper proposes an information theory
      framework to measure information flowing among subsets of functional networks
      call functional domains. NEW METHOD: Our method aims at estimating bits of
      information contained and shared among domains. The succession of dynamic
      functional states is estimated at the domain level. Information quantity is based
      on the probabilities of observing each dynamic state. Mutual information
      measurement is then obtained from probabilities across domains. Thus, we named
      this value the cross domain mutual information (CDMI). RESULTS: Strong CDMIs were
      observed in relation to the subcortical domain. Domains related to sensorial
      input, motor control and cerebellum form another CDMI cluster. Information flow
      among other domains was seldom found. COMPARISON WITH EXISTING METHODS: Other
      methods of dynamic connectivity focus on whole brain dFNC matrices. In the
      current framework, information theory is applied to states estimated from pairs
      of multi-network functional domains. In this context, we apply information theory
      to measure information flow across functional domains. CONCLUSION: Identified
      CDMI clusters point to known information pathways in the basal ganglia and also
      among areas of sensorial input, patterns found in static functional connectivity.
      In contrast, CDMI across brain areas of higher level cognitive processing follow
      a different pattern that indicates scarce information sharing. These findings
      show that employing information theory to formally measured information flow
      through brain domains reveals additional features of functional connectivity.

PMID- 28442298
TI  - How to study and overcome tumor heterogeneity with circulating biomarkers: The
      breast cancer case.
AB  - Breast cancer ranks first among female cancer-related deaths in Western
      countries. As the primary tumor can often be controlled by surgical resection,
      the survival of women with breast cancer is closely linked to the incidence of
      distant metastases. Molecular screening by next generation sequencing highlighted
      the spatial and temporal heterogeneity of solid tumors as well as the clonal
      evolution of cancer cells during progression and under treatment pressure. Such
      findings question whether an optimal assessment of disease progression and a
      screening for druggable mutations should be based on molecular features of
      primary or recurrent/metastatic lesions and therefore represent a crucial element
      for failure or success of personalized medicine. In fact, new targeted therapies
      may induce only short-term benefit annulled by the emergence of resistant clones
      with new driver mutations which would need to be rapidly and reliably identified.
      Serial tissue sampling is therefore essential but, unfortunately, also represents
      a problem since biopsies from solid lesions, which are invasive and potentially
      painful and risky, cannot be easily repeatedly sampled, are inaccessible or may
      not fully reflect tumor heterogeneity. The need to early detect and strike this
      "moving target" is now directing the scientific community toward liquid biopsy
      based biomarkers, which include circulating tumor cells (CTC) and cell-free
      circulating tumor DNA (ctDNA), can be repeatedly assessed through non-invasive
      and easy-to-perform procedures and may act as reliable read-outs of functional
      and molecular features of recurrent/metastatic lesions. In this review we
      summarize the outcome of CTCs and ctDNA in breast cancer, with special reference
      on their role on unveiling and overcoming tumor heterogeneity, on their potential
      relevance for tumor surveillance and monitoring, and for the selection of
      therapeutic options. Finally, we propose integration between blood-based
      molecular and clinical approaches for monitoring disease progression according to
      the specific pattern of recurrence of the most aggressive breast cancer molecular
      subtypes.

PMID- 28442297
TI  - Vertebral and femoral bone mineral density and bone strength in prostate cancer
      patients assessed in phantomless PET/CT examinations.
AB  - PURPOSE: Bone fracture risk assessed ancillary to positron emission tomography
      with computed tomography co-registration (PET/CT) could provide substantial
      clinical value to oncology patients with elevated fracture risk without
      introducing additional radiation dose. The purpose of our study was to
      investigate the feasibility of obtaining valid measurements of bone mineral
      density (BMD) and finite element analysis-derived bone strength of the hip and
      spine using PET/CT examinations of prostate cancer patients by comparing against
      values obtained using routine multidetector-row computed tomography (MDCT) scans
      as validated in previous studies-as a reference standard. MATERIALS AND METHODS:
      Men with prostate cancer (n=82, 71.6+/-8.3 years) underwent Fluorine-18 NaF
      PET/CT and routine MDCT within three months. Femoral neck and total hip areal
      BMD, vertebral trabecular BMD and femur and vertebral strength based on finite
      element analysis were assessed in 63 paired PET/CT and MDCT examinations using
      phantomless calibration and Biomechanical-CT analysis. Men with osteoporosis or
      fragile bone strength identified at either the hip or spine (vertebral trabecular
      BMD <=80mg/cm3, femoral neck or total hip T-score <=-2.5, vertebral strength
      <=6500N and femoral strength <=3500N, respectively) were considered to be at high
      risk of fracture. PET/CT- versus MDCT-based BMD and strength measurements were
      compared using paired t-tests, linear regression and by generating Bland-Altman
      plots. Agreement in fracture-risk classification was assessed in a contingency
      table. RESULTS: All measurements from PET/CT versus MDCT were strongly correlated
      (R2=0.93-0.97; P<0.0001 for all). Mean differences for total hip areal BMD
      (0.001g/cm2, 1.1%), femoral strength (-60N, 1.3%), vertebral trabecular BMD
      (2mg/cm3, 2.6%) and vertebral strength (150N; 1.7%) measurements were not
      statistically significant (P>0.05 for all), whereas the mean difference in
      femoral neck areal BMD measurements was small but significant (-0.018g/cm2; 
      2.5%; P=0.007). The agreement between PET/CT and MDCT for fracture-risk
      classification was 97% (0.89 kappa for repeatability). CONCLUSION: Ancillary
      analyses of BMD, bone strength, and fracture risk agreed well between PET/CT and
      MDCT, suggesting that PET/CT can be used opportunistically to comprehensively
      assess bone integrity. In subjects with high fracture risk such as cancer
      patients this may serve as an additional clinical tool to guide therapy planning
      and prevention of fractures.

PMID- 28442299
TI  - The anti-inflammatory function of high-density lipoprotein in type II diabetes: A
      systematic review.
AB  - BACKGROUND: Inflammation is a pathophysiological factor in diabetes and its
      cardiovascular complications. High-density lipoprotein (HDL) suppresses
      inflammation in healthy individuals. The relationship of HDL with diabetes and
      cardiovascular disease may be explained by HDL function rather than by HDL
      cholesterol level. In diabetes, HDL seems to become dysfunctional. OBJECTIVE: We
      performed a systematic review to answer the following research questions: Is the
      anti-inflammatory function of HDL diminished in individuals with diabetes and if
      so, what causes this? METHODS: We systematically searched Medline and Embase and
      included original research articles on the anti-inflammatory effects of HDL or
      HDL-based interventions in diabetes or diabetes models. We assessed the risk of
      bias of all included studies. RESULTS: Fourteen studies were included. These
      showed great heterogeneity in methodology, study populations, and diabetes
      models. Overall, HDL from subjects with type II diabetes displayed a reduced
      ability to suppress inflammatory processes and inflammation markers. However, the
      mechanisms and the in vivo effects remain largely unknown. No studies reported on
      HDL from individuals with other types of diabetes. In most studies, the risk of
      bias was high or could not be assessed. CONCLUSIONS: HDL isolated from
      individuals with type II diabetes showed a decreased ability to suppress
      inflammation. However, the direction of causality and the underlying mechanisms
      are unknown and should be investigated. For development of treatments directed at
      restoring HDL anti-inflammatory function in diabetes, a standardized method for
      assessing HDL anti-inflammatory function needs to be developed and in vivo
      biomarkers must be identified.

PMID- 28442301
TI  - Dystonia due to bilateral caudate hemorrhage associated with a COL4A1 mutation.

PMID- 28442300
TI  - Effects of MMP12 on cell motility and inflammation during corneal epithelial
      repair.
AB  - Corneal epithelial defects are a common cause of ocular morbidity and can result
      in corneal scarring if they do not heal properly. Matrix metalloproteinases
      (MMPs) are extracellular matrix proteinases that regulate multiple aspects of
      corneal repair. We have previously shown that MMP12 has a protective effect on
      corneal fibrosis through its regulation of neutrophil and macrophage infiltration
      and angiogenesis in a chemical injury model involving full thickness damage to
      the cornea. However, the role of MMP12 in injuries limited to the corneal
      epithelium is relatively unknown. This study investigates the reparative effects
      of MMP12 following isolated corneal epithelial injury. Using a corneal epithelial
      debridement injury model performed on corneas of wild-type (WT) mice, we show
      that Mmp12 is expressed early following corneal epithelial injury with highest
      expression levels at 8 h after injury and lower expression levels at 4 and 8 days
      after injury. We investigated whether MMP12 has an effect on the rate of
      epithelial repair and cell migration using in vivo and in vitro scratch assays
      performed on WT and Mmp12-/- mice. We found that loss of MMP12 results in a
      slower scratch wound repair rate both in vivo and in vitro. We also found that
      corneas of Mmp12-/- mice have decreased neutrophil infiltration following injury.
      Loss of MMP12, however, does not affect cell proliferation in the center of the
      wounds. These data support a role of MMP12 in promoting early repair processes
      following corneal epithelial injury by enhancing epithelial cell migration and
      neutrophil infiltration.

PMID- 28442302
TI  - Facial twitches in ADCY5-associated disease - Myokymia or myoclonus? An
      electromyography study.
AB  - OBJECTIVE: A clinical feature in patients with ADCY5 gene mutations are perioral
      muscle twitches initially described as facial myokymia. METHODS: Five patients
      with ADCY5-associated disease with facial twitches and truncal jerks underwent
      electrophysiological investigations of the orbicularis oris and trapezius muscles
      to delineate neurophysiological characteristics of these phenomena. RESULTS:
      Electromyography (EMG) recordings showed a complex electrophysiological pattern
      with brief bursts of less than 100 ms and longer bursts with a duration of 100
      300 ms up to several seconds in keeping with myoclonus and chorea, respectively,
      as key findings. None of the patients had EMG patterns of myokymia. CONCLUSIONS:
      In this series of five ADCY5 mutation carriers, perioral twitches and truncal
      jerks do not represent myokymia. In view of characteristic clinical signs and
      electrophysiological patterns with a combination of myoclonus and chorea it might
      be preferable to refer to these phenomena as myoclonus-chorea.

PMID- 28442303
TI  - Clinical evaluation of ropinirole controlled-release formulation at 18-24 mg/day
      in Japanese patients with Parkinson's disease.
AB  - INTRODUCTION: There has been no clinical data on Japanese patients with
      Parkinson's disease with which to examine whether motor symptoms improve and to
      assess the safety profile after the dose of ropinirole was increased in those who
      had not achieved an optimal response to the ropinirole immediate-release
      formulation 15 mg/day or the controlled-release (CR) formulation 16 mg/day.
      METHODS: This was a multicenter, randomized, double-blind study, followed by an
      open-label, long-term study. Participants were randomized at a ratio of 3:1 to
      the high-dose ropinirole CR (18-24 mg/day) group or the maintenance ropinirole CR
      16 mg/day group. RESULTS: In the high-dose ropinirole CR group (N = 61), the
      Japanese unified Parkinson's disease rating scale Part III total score at week 12
      was significantly decreased compared with the baseline total score (-4.8 +/-
      5.95, [95% CI, -6.3 to -3.2], p < 0.001). However, a comparable decrease was also
      observed in the maintenance ropinirole CR 16 mg/day group (N = 20) (-5.7 +/-
      5.18, [95% CI, -8.1 to -3.3]), with no statistically significant difference in
      the adjusted mean change between the high-dose and maintenance groups (0.5 [95%
      CI, -2.4 to 3.4]). Plasma drug concentrations increased at doses higher than 16
      mg/day, but did not increase significantly in a dose-dependent manner at doses of
      18-24 mg/day. No adverse events were found that would affect the known safety
      profile of ropinirole. CONCLUSION: This study did not demonstrate the difference
      in efficacy between the high-dose ropinirole CR group and the maintenance
      ropinirole CR group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01929317.

PMID- 28442304
TI  - Topography of essential tremor.
AB  - INTRODUCTION: Topography of tremor manifestations is poorly investigated in
      essential tremor. The present study explores the prevalence and clinical
      correlates of head and/or voice tremor in essential tremor. METHODS: Out of a
      prospectively designed registry of 972 patients, 884 patients with definite and
      probable essential tremor had complete information on tremor localization.
      Demographic and clinical characteristics were compared among four subgroups:
      group A (without head or voice tremor, n = 619), B (with head but without voice
      tremor, n = 155), C (with voice but without head tremor, n = 47), and D (with
      both head and voice tremor, n = 63). RESULTS: In our patients, total prevalence
      of tremor was 24.7% for head, 12.4% for voice and 7.1% for the combination of
      head and voice. Logistic regression analyses showed that female gender is
      strongly associated with head tremor, which was confirmed by an additional meta
      analysis. Severe hand tremor was the only factor associated with voice tremor.
      Both female gender and severe hand tremor increase the odds for having the
      combination of head and voice tremor. For males, hand tremor severity is
      significantly increased among those with head and voice tremor alone and in
      combination, but for females only for the combination. Patients with both head
      and voice tremor have more frequent involvement of legs and other localizations
      and are less responsive to beta-blockers. CONCLUSIONS: Female gender and severe
      hand tremor may increase the odds of head and/or voice tremor in essential
      tremor. The association of hand tremor severity with midline tremor is stronger
      for males than females.

PMID- 28442305
TI  - Transfer of KPC-2 carbapenemase from Klebsiella pneumoniae to Enterobacter
      cloacae in a patient receiving meropenem therapy.
AB  - The horizontal transfer of a plasmid bearing the blaKPC-2 gene from K. pneumoniae
      to E. cloacae infecting the respiratory tract of a patient during meropenem
      therapy was elucidated. This finding is particularly worrisome, since these drugs
      are of last resort for multidrug-resistant Gram-negative pathogens.

PMID- 28442306
TI  - Evaluation of a real-time PCR assay for rectal screening of OXA-48-producing
      Enterobacteriaceae in a general intensive care unit of an endemic hospital.
AB  - Carbapenemase-producing Enterobacteriaceae are increasing worldwide. Rectal
      screening for these bacteria can inform the management of infected and colonized
      patients, especially those admitted to intensive care units (ICUs). A laboratory
      developed, qualitative duplex real-time polymerase chain reaction assay for rapid
      detection of OXA-48-like and VIM producing Enterobacteriaceae, performed on
      rectal swabs, was designed and evaluated in an intensive care unit with endemic
      presence of OXA-48. During analytical assay validation, no cross-reactivity was
      observed and 100% sensitivity and specificity were obtained for both blaOXA-48
      like and blaVIM in all spiked clinical samples. During the clinical part of the
      study, the global sensitivity and specificity of the real-time PCR assay for OXA
      48 detection were 95.7% and 100% (P=0.1250), respectively, in comparison with
      culture; no VIM-producing Enterobacteriaceae were detected. Clinical features of
      patients in the ICU who were colonized or infected with OXA-48 producing
      Enterobacteriaceae, including outcome, were analyzed. Most had severe underlying
      conditions, and had risk factors for colonization with carbapenemase-producing
      Enterobacteriaceae before or during ICU admission, such as receiving previous
      antimicrobial therapy, prior healthcare exposure (including long-term care),
      chronic disease, immunosuppression and/or the presence of an intravascular
      catheter and/or mechanical ventilation device. The described real-time PCR assay
      is fast (~2-3hours, if DNA extraction is included), simple to perform and results
      are easy to interpret, features which make it applicable in the routine of
      clinical microbiology laboratories. Implementation in endemic hospitals could
      contribute to early detection of patients colonized by OXA-48 producing
      Enterobacteriaceae and prevention of their spread.

PMID- 28442308
TI  - 18F-FDG PET/CT in aggressive angiomyxoma of the pelvis.

PMID- 28442307
TI  - Association between Body Mass Index, C-Reactive Protein Levels, and Melanoma
      Patient Outcomes.

PMID- 28442309
TI  - A universal colorimetry for nucleic acids and aptamer-specific ligands detection
      based on DNA hybridization amplification.
AB  - We present a universal amplified-colorimetric for detecting nucleic acid targets
      or aptamer-specific ligand targets based on gold nanoparticle-DNA (GNP-DNA)
      hybridization chain reaction (HCR). The universal arrays consisted of capture
      probe and hairpin DNA-GNP. First, capture probe recognized target specificity and
      released the initiator sequence. Then dispersed hairpin DNA modified GNPs were
      cross-linked to form aggregates through HCR events triggered by initiator
      sequence. As the aggregates accumulate, a significant red-to purple color change
      can be easily visualized by the naked eye. We used miRNA target sequence (miRNA
      203) and aptamer-specific ligand (ATP) as target molecules for this proof-of
      concept experiment. Initiator sequence (DNA2) was released from the capture probe
      (MNP/DNA1/2 conjugates) under the strong competitiveness of miRNA-203. Hairpin
      DNA (H1 and H2) can be complementary with the help of initiator DNA2 to form GNP
      H1/GNP-H2 aggregates. The absorption ratio (A620/A520) values of solutions were a
      sensitive function of miRNA-203 concentration covering from 1.0 * 10-11 M to 9.0
      * 10-10 M, and as low as 1.0 * 10-11 M could be detected. At the same time, the
      color changed from light wine red to purple and then to light blue have occurred
      in the solution. For ATP, initiator sequence (5'-end of DNA3) was released from
      the capture probe (DNA3) under the strong combination of aptamer-ATP. The present
      colorimetric for specific detection of ATP exhibited good sensitivity and 1.0 *
      10-8 M ATP could be detected. The proposed strategy also showed good performances
      for qualitative analysis and quantitative analysis of intracellular nucleic acids
      and aptamer-specific ligands.

PMID- 28442310
TI  - COPD-OSA Overlap Syndrome: Evolving Evidence Regarding Epidemiology, Clinical
      Consequences, and Management.
AB  - COPD and OSA are both highly prevalent, which implies that both disorders
      occurring together (overlap syndrome) is likely to be common based on chance
      association alone. However, different clinical COPD phenotypes influence the
      likelihood of coexisting OSA in that the increased lung volumes and low BMI
      associated with the predominant emphysema phenotype protects against OSA, whereas
      the higher likelihood of peripheral edema and increased BMI associated with the
      predominant chronic bronchitis phenotype promotes OSA. Both COPD and OSA are
      associated with similar physiological and molecular consequences, such as hypoxia
      and systemic inflammation, that contribute to cardiovascular and other
      comorbidities, and pulmonary hypertension is highly prevalent in patients with
      the overlap syndrome. However, there have been few published reports that have
      evaluated systemic inflammation and other cardiovascular comorbidities in
      patients with overlap syndrome. The diagnosis of OSA in patients with COPD
      requires awareness of relevant clinical features, and screening questionnaires
      may help identify suitable patients for further overnight study. The recognition
      of coexisting OSA in patients with COPD has important clinical relevance, as the
      management of patients with overlap syndrome is different from the management of
      COPD alone, and the survival of patients with overlap syndrome that is not
      treated with nocturnal positive airway pressure is significantly inferior to that
      of patients with overlap syndrome that is appropriately treated.

PMID- 28442311
TI  - Sleep Phase Delay in Cystic Fibrosis: A Potential New Manifestation of Cystic
      Fibrosis Transmembrane Regulator Dysfunction.
AB  - BACKGROUND: Cystic fibrosis (CF) transmembrane regulator (CFTR) protein
      dysfunction causes CF. Improving survival allows detection of increasingly subtle
      disease manifestations. CFTR dysfunction in the central nervous system (CNS) may
      disturb circadian rhythm and thus sleep phase. We studied sleep in adults to
      better understand potential CNS CFTR dysfunction. METHODS: We recruited
      participants from April 2012 through April 2015 and administered the Munich
      Chronotype Questionnaire (MCTQ). We compared free-day sleep measurements between
      CF and non-CF participants and investigated associations with CF survival
      predictors. RESULTS: We recruited 23 female and 22 male adults with CF aged 18 to
      46 years and 26 female and 22 male volunteers aged 18 to 45 years. Compared with
      volunteers without CF, patients with CF had delayed sleep onset (0.612 h; P =
      .015), midsleep (1.11 h; P < .001), and wake (1.15 h; P < .001) times and
      prolonged sleep latency (7.21 min; P = .05) and duration (0.489 h; P = .05).
      Every hour delay in sleep onset was associated with shorter sleep duration by
      0.29 h in patients with CF and 0.75 h in subjects without CF (P = .007) and
      longer sleep latency by 7.51 min in patients with CF and 1.6 min in volunteers
      without CF (P = .035). Among patients with CF, FEV1 % predicted, prior acute
      pulmonary exacerbations, and weight were independent of all free-day sleep
      measurements. CONCLUSIONS: CF in adults is associated with marked delays in sleep
      phase consistent with circadian rhythm phase delays. Independence from disease
      characteristics predictive of survival suggests that sleep phase delay is a
      primary manifestation of CFTR dysfunction in the CNS.

PMID- 28442312
TI  - Expert Statements on the Standard of Care in Critically Ill Adult Patients With
      Atypical Hemolytic Uremic Syndrome.
AB  - A typical hemolytic uremic syndrome (aHUS) presents similarly to thrombotic
      thrombocytopenic purpura (TTP) and other causes or conditions with thrombotic
      microangiopathy (TMA), such as disseminated intravascular coagulation or sepsis.
      Similarity in clinical presentation may hinder diagnosis and optimal treatment
      selection in the urgent setting in the ICU. However, there is currently no
      consensus on the diagnosis or treatment of aHUS for ICU specialists. This review
      aims to summarize available data on the diagnosis and treatment strategies of
      aHUS in the ICU to enhance the understanding of aHUS diagnosis and outcomes in
      patients managed in the ICU. To this end, a review of the recent literature
      (January 2009-March 2016) was performed to select the most relevant articles for
      ICU physicians. Based on the paucity of adult aHUS cases overall and within the
      ICU, no specific recommendations could be formally graded for the critical care
      setting. However, we recognize a core set of skills required by intensivists for
      diagnosing and managing patients with aHUS: recognizing thrombotic
      microangiopathies, differentiating aHUS from related conditions, recognizing
      involvement of other organ systems, understanding the pathophysiology of aHUS,
      knowing the diagnostic workup and relevant outcomes in critically ill patients
      with aHUS, and knowing the standard of care for patients with aHUS based on
      available data and guidelines. In conclusion, managing critically ill patients
      with aHUS requires basic skills that, in the absence of sufficient data from
      patients treated within the ICU, can be gleaned from an increasingly relevant
      literature outside the ICU. More data on critically ill patients with aHUS are
      needed to validate these conclusions within the ICU setting.

PMID- 28442313
TI  - The Role of Neutrophil Elastase Inhibitors in Lung Diseases.
AB  - In many respiratory diseases characterized by an intense inflammatory response,
      the balance between proteolytic enzymes (proteases, including elastases) and
      their inhibitors (proteinases inhibitors) is not neutral. Excess activity of
      neutrophil elastase (NE) and similar proteases has been reported to cause tissue
      damage and to alter the remodeling process in many clinical conditions such as
      pneumonia, respiratory distress, and acute lung injury (ALI). Several
      experimental NE inhibitors have been tested in preclinical and clinical studies
      of different conditions of inflammatory lung injury such as ALI and pneumonia,
      with contrasting results. This study reviews the literature regarding NE
      inhibitors in the field of respiratory diseases and reflects on possible future
      developments. In particular, we highlight potential gaps in the scientific
      evidence and discuss potential strategies for focusing investigation on
      antielastases in clinical practice through the selection of targeted populations
      and proper outcomes.

PMID- 28442315
TI  - Healing Marginal Ulcers in Patients Who Have Had a Roux-en-Y Gastric Bypass.

PMID- 28442314
TI  - Photodynamic therapy in the management of basal cell carcinoma: Retrospective
      evaluation of outcome.
AB  - INTRODUCTION: Photodynamic therapy (PDT) is a relatively new method of treating
      various kinds of pathologies. In this retrospective study, a total of 148
      patients with basal cell carcinoma (BCC) were treated with surface illumination
      methyl aminolevulinate - photodynamic therapy (MAL-PDT) or meta
      tetrahydroxyphenylchlorin (mTHPC-PDT). Comparisons with the clinical features,
      rate of recurrence and overall outcome were made. MATERIALS AND METHODS: Surface
      illumination PDT was offered under local or general anaesthesia. For thin BCCs,
      the 16% strength cream (MAL) was applied topically 3h prior to tissue
      illumination. A single-channel 628nm diode laser was used for illumination and
      light was delivered at 100J/cm2 per site. For thick BCCs, 0.05mg/kg mTHPC was
      administered intravenously prior to tissue illumination. A single-channel 652nm
      diode laser was used for illumination and light was delivered at 20J/cm2 per
      site. Lesion response evaluation was carried out according to RECIST. RESULTS:
      The MAL-PDT sub-group included 86 patients with 127 thin BCCs; 80 patients had
      complete response (CR) after one round of treatment. The mTHPC-PDT sub-group
      included 62 patients with 116 thick BCCs; 60 patients had complete response after
      one round of treatment. Statistically significant factors associated with
      complete response to MAL-PDT included superficial BCC histotype (P<0.001),
      <=0.5mm tumour thickness (P<0.001) and lack of ulceration (P<0.001). While for
      the mTHPC-PDT sub-group, both superficial and nodular types responded
      significantly better than invasive type (P<0.001); the lack of ulceration was
      insignificant factor in achieving complete response. CONCLUSION: PDT achieved
      high efficacy in the treatment of basal cell carcinomas with greatly reduced
      morbidity and disfigurement. The technique is simple, can commonly be carried out
      in outpatient clinics, and is highly acceptable to patients.

PMID- 28442316
TI  - Endoscopic Balloon Dilation vs Surgery for Crohn's Disease-related Strictures.

PMID- 28442317
TI  - Spontaneous Intramural Esophageal Hematoma.

PMID- 28442318
TI  - Brownian model of transcriptome evolution and phylogenetic network visualization
      between tissues.
AB  - While phylogenetic analysis of transcriptomes of the same tissue is usually
      congruent with the species tree, the controversy emerges when multiple tissues
      are included, that is, whether species from the same tissue are clustered
      together, or different tissues from the same species are clustered together.
      Recent studies have suggested that phylogenetic network approach may shed some
      lights on our understanding of multi-tissue transcriptome evolution; yet the
      underlying evolutionary mechanism remains unclear. In this paper we develop a
      Brownian-based model of transcriptome evolution under the phylogenetic network
      that can statistically distinguish between the patterns of species-clustering and
      tissue-clustering. Our model can be used as a null hypothesis (neutral
      transcriptome evolution) for testing any correlation in tissue evolution, can be
      applied to cancer transcriptome evolution to study whether two tumors of an
      individual appeared independently or via metastasis, and can be useful to detect
      convergent evolution at the transcriptional level.

PMID- 28442319
TI  - A rare case of congenital bronchoesophageal fistula in an adult.
AB  - INTRODUCTION: When congenital bronchoesophageal fistulas exist without atresia of
      the esophagus, the diagnosis can be delayed, although symptoms may occur early
      following fistula development. Therefore, while they are usually found in
      infants, they can be extremely rarely found in adults. We herein report a rare
      case of bronchoesophageal fistula without atresia in an adult. CASE: An 69-year
      old male presented to the outpatient clinic with a decades-long history of cough
      with expectoration immediately after taking food, especially liquids. Computed
      tomograph, esophagoscopy, and esophagography revealed the fistulous communication
      between the mid-esophagus and right lower lobe bronchus, with consolidation in
      the right lower lobe. We performed right lower lobectomy with the closure and
      excision of the fistula. The histopathology of the fistula revealed the mucosa to
      be lined by stratified squamous epithelium. There was no evidence of
      inflammation, granuloma, or carcinoma. CONCLUSION: In conclusion, despite the
      benign nature of this malformation, if left untreated, it can cause long-term
      debilitating respiratory symptoms associated with the fistula. Therefore, the
      diagnosis should be considered in the evaluation of recurrent lung infection.

PMID- 28442320
TI  - People with multiple sclerosis report significantly worse symptoms and health
      related quality of life than the US general population as measured by PROMIS and
      NeuroQoL outcome measures.
AB  - BACKGROUND: Individuals with multiple sclerosis (MS) report fatigue, pain,
      depression, cognitive difficulties, and other symptoms. It is often difficult to
      compare symptoms across studies and populations because scales used to measure
      individual symptoms or quality of life indicators (QOLI) use different metrics
      and often do not provide norms. PROMIS and Neuro-QOL measures, developed with
      modern psychometric methods, use a common metric and provide population norms.
      OBJECTIVE: To create symptom profiles and compare symptoms and QOLIs of people
      living with MS to a US general population sample. METHODS: Data from
      observational cross-sectional survey studies of 1544 community dwelling
      individuals with MS were analyzed. T-tests and non-parametric tests were used to
      examine whether symptoms or QOLIs of people with MS differed from the general US
      population. Regression analyses were used to adjust differences for age and sex.
      Measures included PROMIS or NeuroQoL anxiety, depression, fatigue, sleep
      disturbance and related impairment, pain interference, physical function,
      satisfaction with social roles, and applied cognition. Symptom levels were also
      compared by age, gender, and disability level. RESULTS: Scores on all health
      domains were statistically significantly (all p < 0.001) worse than the general
      US population and six domains had scores worse by half standard deviation or
      more. These differences remained significant after adjusting for age and sex.
      CONCLUSIONS: Individuals with MS report clinically meaningful worse health
      compared to the general population across multiple health related domains.
      Symptom profiles utilizing PROMIS or NeuroQoL measures can be used to quickly
      assess symptom levels in an individual or group.

PMID- 28442321
TI  - High prevalence of Plasmodium falciparum and soil-transmitted helminth co
      infections in a periurban community in Kwara State, Nigeria.
AB  - Prevalence of malaria and soil-transmitted helminth infections, and the burden of
      disease are enormous in sub-Saharan Africa. Co-infections aggravate the clinical
      outcome, but are common due to an overlap of endemic areas. A cross-sectional
      survey was conducted to assess prevalence, intensity of infection and association
      between malaria and soil-transmitted helminth infections in a typical periurban
      community in Kwara State. Fresh blood and faecal samples were examined using
      thick blood film and Kato-Katz smear techniques. A total of 383/471 study
      participants (81.3%) were infected with at least one parasite species, with the
      following prevalences and mean infection intensities: Plasmodium falciparum 63.7%
      (2313.6 parasites/MUl); Ascaris lumbricoides 63.1% (3152.1 epg); Trichuris
      trichiura 53.3% (1043.5 epg); and hookworms 30.1% (981.7 epg). Sixty-three
      percent of the study population were co-infected with two or more parasite
      species. The prevalence of ascariasis was significantly higher in individuals
      infected with P. falciparum (adjusted OR: 5.87; 95% CI: 3.30-10.42). Heavy A.
      lumbricoides and T. trichiura infections were associated with high P. falciparum
      parasitaemia. Co-endemicity of malaria and soil transmitted helminth infections
      is an important public health problem in the study area. Multi-target integrated
      approaches focusing on disease intervention are essential to mitigate morbidity
      caused by multiple infections.

PMID- 28442322
TI  - In vitro and in vivo antitumor activities of T-3764518, a novel and orally
      available small molecule stearoyl-CoA desaturase 1 inhibitor.
AB  - Most cancer cells are characterized by elevated lipid biosynthesis. The rapid
      proliferation of cancer cells requires de novo synthesis of fatty acids. Stearoyl
      CoA desaturase-1 (SCD1), a key enzyme for lipogenesis, is overexpressed in
      various types of cancer and plays an important role in cancer cell proliferation.
      Therefore, it has been studied as a candidate target for cancer therapy. In this
      study, we demonstrate the pharmacological properties of T-3764518, a novel and
      orally available small molecule inhibitor of SCD1. T-3764518 inhibited stearoyl
      CoA desaturase-catalyzed conversion of stearoyl-CoA to oleoyl-CoA in colorectal
      cancer HCT-116 cells and their growth. Further, it slowed tumor growth in an HCT
      116 and a mesothelioma MSTO-211H mouse xenograft model. Comprehensive lipidomic
      analyses revealed that T-3764518 increases the membrane ratio of saturated:
      unsaturated fatty acids in various lipid species such as phosphatidylcholines and
      diacylglycerols in both cultured cells and HCT-116 xenografts. Treatment
      associated lipidomic changes were followed by activated endoplasmic reticulum
      (ER) stress responses such as increased immunoglobulin heavy chain-binding
      protein expression in HCT-116 cells. These T-3764518-induced changes led to an
      increase in cleaved poly (ADP-ribose) polymerase 1 (PARP1), a marker of
      apoptosis. Additionally, bovine serum albumin conjugated with oleic acid, an SCD1
      product, prevented cell growth inhibition and ER stress responses by T-3764518,
      indicating that these outcomes were not attributable to off-target effects. These
      results indicate that T-3764518 is a promising new anticancer drug candidate.

PMID- 28442323
TI  - The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following
      angiotensin-II type 1 receptor blockade.
AB  - The renin angiotensin system (RAS) regulates numerous systemic functions and is
      expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial
      member of the RAS, and the therapeutic effects of a large number of angiotensin
      receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study
      examines whether the reported osteo-preservative effects of losartan are mediated
      through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in
      ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d
      p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini
      osmotic pumps during the losartan treatment period. Serum and urine bone
      metabolism biomarker levels were measured. Bone trabecular and cortical
      morphometry were quantified in distal femurs, whereas mineral contents were
      estimated in ashed bones, serum and urine. Finally, the expression of RAS
      components, the receptor activator of NF-kappaB ligand (RANKL) and
      osteoprotegerin (OPG) was determined. Losartan significantly improved the
      elevated bone metabolism marker levels and altered trabecular and cortical
      structures in OVX animals, and restored normal urinary and skeletal mineral
      levels. Mas receptor inhibition significantly abolished all osteo-protective
      effects of losartan and enhanced the deleterious effects of OVX. Losartan
      enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT1)
      receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG
      expression in OVX animals. However, A-779 significantly eradicated the effects of
      losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in
      the osteo-preservative effects of losartan via Mas receptor, which may add
      therapeutic value to this well-known antihypertensive agent.

PMID- 28442324
TI  - The interactive role of CB1 receptors and L-type calcium channels in hippocampal
      long-term potentiation in rats.
AB  - Long-term potentiation (LTP) of synaptic responses is a widely researched model
      of synaptic plasticity that occurs during learning and memory. The cannabinoid
      system is an endogenous system that modulate this kind of synaptic plasticity. In
      addition, voltage dependent calcium channels is essential for induction of LTP at
      some synapses in the hippocampus. However, there is currently debate over the
      interaction between L-type calcium channels and cannabinoid system on the
      synaptic plasticity. In this study, we examined the effects of an acute
      administration of the cannabinoid antagonist AM251 following a chronic
      administration of the Ca2+ channel blocker verapamil on LTP induction in the
      hippocampal dentate gyrus(DG) of rats. Male Wistar rats were administered
      verapamil(10,25,50mg/kg) or saline intraperitoneally(IP) daily for
      13days(n=10/group). After this treatment period, animals were anesthetized with
      an IP injection of urethane; the recording and stimulating electrodes were
      positioned in the DG and the perforant pathway. After obtaining a steady state
      baseline response, a single IP injection of saline or AM251(1 or 5mg/kg) was
      administered. LTP was induced by high-frequency stimulation(HFS). The population
      spike(PS) amplitude and the slope of excitatory postsynaptic potentials(EPSP)
      were compared between the experimental groups. The acute administration of the
      CB1 antagonist AM251 increased LTP induction. The EPSP slopes and PS amplitude in
      the verapamil and AM251 groups differed after HFS, such that AM251 increased LTP,
      whereas verapamil decreased LTP induction. These findings suggest that there are
      functional interactions between the L-type calcium channels and cannabinoid
      system in this model of synaptic plasticity in the hippocampus.

PMID- 28442325
TI  - The antimicrobial peptide human beta-defensin 2 promotes itch through Toll-like
      receptor 4 signaling in mice.

PMID- 28442326
TI  - Inhaled efficacious dose translation from rodent to human: A retrospective
      analysis of clinical standards for respiratory diseases.
AB  - Clinical pharmacologists and toxicologists are often faced with predicting
      equivalent dosages for humans from biological observations in laboratory animals.
      Allometric scaling has been used extensively as the basis for extrapolation of
      drug dosage that might be expected to produce the equivalent biological effects.
      Allometry is the study of size and its consequences and it is based on the
      anatomical, physiological, and biochemical similarities between animals. In this
      review, retrospective analyses have been performed based on data reported in the
      literature in an attempt to determine the utility of allometric scaling for human
      dose projections from pre-clinical data for compounds that are delivered by
      inhalation. The limited pre-clinical efficacy data available on inhaled drugs
      that are also used clinically supports the current method of scaling using a
      fixed allometric exponent of 0.67. An example of the utility of the human inhaled
      dose projections for planning inhaled toxicology studies is also presented.

PMID- 28442327
TI  - Sample preservation, transport and processing strategies for honeybee RNA
      extraction: Influence on RNA yield, quality, target quantification and data
      normalization.
AB  - Viral infections in managed honey bees are numerous, and most of them are caused
      by viruses with an RNA genome. Since RNA degrades rapidly, appropriate sample
      management and RNA extraction methods are imperative to get high quality RNA for
      downstream assays. This study evaluated the effect of various sampling-transport
      scenarios (combinations of temperature, RNA stabilizers, and duration) of
      transport on six RNA quality parameters; yield, purity, integrity, cDNA synthesis
      efficiency, target detection and quantification. The use of water and extraction
      buffer were also compared for a primary bee tissue homogenate prior to RNA
      extraction. The strategy least affected by time was preservation of samples at 
      80 degrees C. All other regimens turned out to be poor alternatives unless the
      samples were frozen or processed within 24h. Chemical stabilizers have the
      greatest impact on RNA quality and adding an extra homogenization step (a
      QIAshredderTM homogenizer) to the extraction protocol significantly improves the
      RNA yield and chemical purity. This study confirms that RIN values (RNA Integrity
      Number), should be used cautiously with bee RNA. Using water for the primary
      homogenate has no negative effect on RNA quality as long as this step is no
      longer than 15min.

PMID- 28442328
TI  - Simple, quick and cost-efficient: A universal RT-PCR and sequencing strategy for
      genomic characterisation of foot-and-mouth disease viruses.
AB  - Foot-and-mouth disease (FMD) is a major contributor to poverty and food
      insecurity in Africa and Asia, and it is one of the biggest threats to
      agriculture in highly developed countries. As FMD is extremely contagious,
      strategies for its prevention, early detection, and the immediate
      characterisation of outbreak strains are of great importance. The generation of
      whole-genome sequences enables phylogenetic characterisation, the epidemiological
      tracing of virus transmission pathways and is supportive in disease control
      strategies. This study describes the development and validation of a rapid,
      universal and cost-efficient RT-PCR system to generate genome sequences of FMDV,
      reaching from the IRES to the end of the open reading frame. The method was
      evaluated using twelve different virus strains covering all seven serotypes of
      FMDV. Additionally, samples from experimentally infected animals were tested to
      mimic diagnostic field samples. All primer pairs showed a robust amplification
      with a high sensitivity for all serotypes. In summary, the described assay is
      suitable for the generation of FMDV sequences from all serotypes to allow
      immediate phylogenetic analysis, detailed genotyping and molecular epidemiology.

PMID- 28442329
TI  - Association of Telomere Length With Myocardial Infarction: A Prospective Cohort
      From the Population Based HUNT 2 Study.
AB  - As possible markers of biological age, telomere length (TL) has been associated
      with age-related diseases such as myocardial infarction (MI) with conflicting
      findings. We sought to assess the relationship between TL and risk of future MI
      in 915 healthy participants (51.7% women) 65 years or older from a population
      based prospective cohort (the HUNT 2 study, Norway). Mean TL was measured by
      quantitative PCR expressed as relative T (telomere repeat copy number) to S
      (single copy gene number) ratio, and log-transformed. During a mean follow up of
      13.0 (SD, 3.2) years and 11,923 person-years, 82 participants were diagnosed with
      MI. We used Cox proportional hazard regressions to estimate hazard ratios (HR)
      and 95% confidence interval (CI). Relative TL was associated with age in women
      (P=0.01), but not in men (P=0.43). Using relative TL as a continuous variable, we
      observed a higher risk of MI in participants with longer telomeres with HRs of
      2.46 (95% CI; 1.13 to 4.54) in men, and 2.93 (95% CI; 1.41 to 6.10) in women.
      Each 1-SD change in relative TL was associated with an HR of 1.54 (95% CI; 1.15
      to 2.06) and 1.67 (95% CI; 1.18 to 2.37) in men and women, respectively. Compared
      with the bottom tertile of relative TL, HR of incident MI in top tertile was 2.71
      (95% CI; 1.25 to 5.89) in men, and 3.65 (95% CI; 1.35 to 9.90) in women. Longer
      telomeres in healthy participants 65 years or older are associated with a high
      risk of incident MI. Future large scale prospective studies are needed to confirm
      these findings and explore the potential association between TL and MI.

PMID- 28442330
TI  - Symptomatic Carotid Artery Disease: Revascularization.
AB  - Patients with symptomatic carotid artery disease should be managed by a
      multidisciplinary team including neurologists, vascular surgeons and
      interventionalists. Duplex ultrasound is the most widely used diagnostic modality
      to assess carotid disease, followed by additional imaging tests (CT- or MR
      angiography) to confirm the severity of the stenosis, detect brain lesions, and
      assess intracranial circulation as well as the supra-aortic anatomy. Although
      overall randomized trial results favored (CEA) over carotid artery stenting (CAS)
      in symptomatic patients, this was likely related to the insufficient expertise of
      the endovascular specialists in several of the trials. CAS should be considered
      as a valid alternative to CEA in patients with favorable anatomy and in those at
      high-surgical risk, provided it is performed by experienced operators in high
      volume centers. Under those circumstances, it is reasonable to offer the patients
      the two options (CEA or CAS) after description of pros and cons of each therapy.
      CAS results may be further improved by better patient selection, new techniques,
      and technology advancements.

PMID- 28442331
TI  - Non-covalent conjugation of cutinase from Fusarium sp. ICT SAC1 with pectin for
      enhanced stability: Process minutiae, kinetics, thermodynamics and structural
      study.
AB  - Cutinase, a member of alpha/beta-fold hydrolase family possess potentially
      diverse applications in several industrial processes and products. The present
      work aims towards thermo-stabilization of cutinase from novel source Fusarium sp.
      ICT SAC1 via non-covalent interaction with polysaccharides. Although all six
      polysaccharides chosen for study enhanced the thermal stability, pectin was found
      to be most promising. The interaction protocol for cutinase with pectin was
      optimized sequentially with respect to the ratio of enzyme to pectin, solution
      pH, and buffer strength. Cutinase-pectin conjugate under optimized conditions
      (1:12, pH-6.5, 50mM) showed enhanced thermal stability as evident from lower
      inactivation rate constant, higher half-life and D-value within the 40-55 degrees
      C. A slender rise in Km and Vmax values and enhanced thermodynamic parameters of
      cutinase-pectin conjugate were observed after non-covalent interaction. Entropy
      values were 1.5-fold higher for cutinase-pectin conjugate at each temperature
      suggesting an upsurge in number of protein molecules in a transition activated
      state. Positive values of entropy for both forms of cutinase suggested a rise in
      disordered conformation. Noticeable conformational changes in cutinase after
      conjugation with pectin were confirmed by FTIR as well as fluorescence emission
      spectra. An increment in helix to turn conversion was observed in complexed
      cutinase vis-a-vis free cutinase.

PMID- 28442332
TI  - The individual preferred velocity of stroking touch as a stable measurement.
AB  - Affective touch is of fundamental importance in human social interactions and
      there is an increasing interest in using touch as a probe for general affective
      perception. To this end, we developed a test of preferred velocity (ToP-V) of
      touch and tested whether the individually preferred stroking velocity is a stable
      and valid measurement. In study one, thirty healthy participants (18-30years, 17
      women) were examined with the ToP-V. Therefore, pairs of different slow stroking
      stimuli were presented by the Rotary Tactile Stimulator - a robotic device - on
      the forearm and the participants chose the velocity they preferred in a forced
      choice paradigm. A retest was conducted after about 12days. In study two, twenty
      two healthy participants (20-43years, 11 women) were tested with a shorter
      version of the ToP-V on the forearm and also on the palm. Moreover, they rated
      the pleasantness and the intensity of the stroking stimulations on both body
      sites. Results suggest that humans possess an individual and stable preferred
      velocity of stroking touch (test-retest reliability r=0.86) which can be tested
      in a standardized procedure. A shortened 5min version of the ToP-V also exhibited
      reasonable test characteristics (split half reliability: r=0.7; test-retest
      reliability r=0.77). The ToP-V correlated well with the pleasantness ratings when
      tested on the forearm (r=0.65), but not when tested on the palm (r=-0.22),
      indicating that the ToP-V targets a C-tactile nerve fiber specific perception.
      Hence, the ToP-V can be used for reliably probing affective touch perception.

PMID- 28442333
TI  - Effects of auditory stimuli on electrical activity in the brain during cycle
      ergometry.
AB  - The present study sought to further understanding of the brain mechanisms that
      underlie the effects of music on perceptual, affective, and visceral responses
      during whole-body modes of exercise. Eighteen participants were administered
      light-to-moderate intensity bouts of cycle ergometer exercise. Each exercise bout
      was of 12-min duration (warm-up [3min], exercise [6min], and warm-down [3min]).
      Portable techniques were used to monitor the electrical activity in the brain,
      heart, and muscle during the administration of three conditions: music,
      audiobook, and control. Conditions were randomized and counterbalanced to prevent
      any influence of systematic order on the dependent variables. Oscillatory
      potentials at the Cz electrode site were used to further understanding of time
      frequency changes influenced by voluntary control of movements. Spectral
      coherence analysis between Cz and frontal, frontal-central, central, central
      parietal, and parietal electrode sites was also calculated. Perceptual and
      affective measures were taken at five timepoints during the exercise bout.
      Results indicated that music reallocated participants' attentional focus toward
      auditory pathways and reduced perceived exertion. The music also inhibited alpha
      resynchronization at the Cz electrode site and reduced the spectral coherence
      values at Cz-C4 and Cz-Fz. The reduced focal awareness induced by music led to a
      more autonomous control of cycle movements performed at light-to-moderate
      intensities. Processing of interoceptive sensory cues appears to upmodulate
      fatigue-related sensations, increase the connectivity in the frontal and central
      regions of the brain, and is associated with neural resynchronization to sustain
      the imposed exercise intensity.

PMID- 28442334
TI  - Pica Practices among Apparently Healthy Women and Their Young Children in Ghana.
AB  - BACKGROUND: Pica is an increased appetite/craving for food or non-food substances
      like clay, and chalk, and is strongly associated with iron deficiency (ID)
      anemia. This study assessed pica practices among non-pregnant mothers and their
      children, 12-to-59 months, in an anaemia endemic population in Ghana. SUBJECTS
      AND METHODS: A cross-sectional quantitative survey was conducted in two randomly
      selected districts in Northern Ghana. The researchers developed semi-structured
      questionnaires with components on pica practice, history and experiences and
      administered via structured face-to-face interviews with mothers (N=161) and all
      their children 6-59 months. Of this population, 132 mothers had children 12-to-59
      months (N=139) in April 2012. Pica practice among children was reported by their
      mothers. Data was analysed using SPSS version 23.0. RESULTS: Few mothers (3%)
      spontaneously reported pica (for uncommon food and/or non-food substances) at the
      time of the interview, however, 16 (12.1%) mothers with pica were confirmed after
      further probing. Twelve (8.6%) children were reported to have ingested/craved
      clay/soil/dust (11 / 91.7 %), paper (1 / 7.1%) and chalk (1/7.1%) prior to the
      interview. One child had poly-pica (pica for two substance). Pica was reported to
      have been practised by expecting mothers during 37 (26.6%) of the pregnancies of
      the children involved in the study, and was mostly for clay/soil (33 / 89.1%),
      kola nut (5 / 3.6%), uncooked rice and bambara beans. Children's pica practices
      were significantly associated (chi2=6.33; p=0.011) with their mothers' pica
      practices during pregnancy as well as with mothers' pica practices at the time of
      the study (chi2=5.98; p=0.035). A logistic regression analysis seemed to show
      that pica of the mother during pregnancy was more strongly associated with the
      child's pica than later pica behaviour of the mother. Many myths and
      misconceptions associated with the practice of pica were also reported in these
      communities. CONCLUSIONS: The reported pica practice among mothers and their
      children was lower than what has been observed in other studies. Knowledge and
      perceptions regarding pica were mostly inaccurate. Education on pica and
      associated dangers of its practices should be included in nutrition interventions
      in communities with known high anemia prevalence.

PMID- 28442335
TI  - Do impulsive individuals benefit more from food go/no-go training? Testing the
      role of inhibition capacity in the no-go devaluation effect.
AB  - Not responding to food items in a go/no-go task can lead to devaluation of these
      food items, which may help people regulate their eating behavior. The Behavior
      Stimulus Interaction (BSI) theory explains this devaluation effect by assuming
      that inhibiting impulses triggered by appetitive foods elicits negative affect,
      which in turn devalues the food items. BSI theory further predicts that the
      devaluation effect will be stronger when food items are more appetitive and when
      individuals have low inhibition capacity. To test these hypotheses, we
      manipulated the appetitiveness of food items and measured individual inhibition
      capacity with the stop-signal task. Food items were consistently paired with
      either go or no-go cues, so that participants responded to go items and not to no
      go items. Evaluations of these items were measured before and after go/no-go
      training. Across two preregistered experiments, we consistently found no-go foods
      were liked less after the training compared to both go foods and foods not used
      in the training. Unexpectedly, this devaluation effect occurred for both
      appetitive and less appetitive food items. Exploratory signal detection analyses
      suggest this latter finding might be explained by increased learning of stimulus
      response contingencies for the less appetitive items when they are presented
      among appetitive items. Furthermore, the strength of devaluation did not
      consistently correlate with individual inhibition capacity, and Bayesian analyses
      combining data from both experiments provided moderate support for the null
      hypothesis. The current project demonstrated the devaluation effect induced by
      the go/no-go training, but failed to obtain further evidence for BSI theory.
      Since the devaluation effect was reliably obtained across experiments, the
      results do reinforce the notion that the go/no-go training is a promising tool to
      help people regulate their eating behavior.

PMID- 28442336
TI  - Observed differences in child picky eating behavior between home and childcare
      locations.
AB  - Picky eating (PE) is a common mealtime difficulty that is reported by up to 50%
      of caregivers. Most of the research to date on PE has focused on parents, even
      though millions of children also eat meals in home- or center-based childcare
      settings. Currently, little is known about PE behaviors manifested by the child
      across the home and childcare settings, or how these behaviors differ between
      home-based childcare (HBCC) and center-based childcare (CBCC) locations. The
      objectives of this study were to compare PE behaviors between the child's home
      and HBCC or CBCC environments, and compare PE behaviors between HBCC and CBCC
      environments. Children, ages 3-5 years, were recruited from CBCC (n = 26) or HBCC
      (n = 24) locations. Caregivers and children were videotaped consuming two
      different lunchtime meals in their home and childcare. Picky eating behaviors
      were coded from the videos using a codebook created for the study. Observational
      results showed that children in CBCC displayed more PE behaviors when at home
      than at childcare, while HBCC children displayed PE behaviors more similarly
      between the two locations. Thus, interventions to reduce PE behaviors should be
      personalized for location-specific intervention programs focused on raising
      healthy eaters across multiple locations.

PMID- 28442337
TI  - The Weight-Related Eating Questionnaire offers a concise alternative to the Three
      Factor Eating Questionnaire for measuring eating behaviors related to weight
      loss.
AB  - OBJECTIVE: During a one-year weight loss trial, we compared the Three-Factor
      Eating Questionnaire (TFEQ), a valid 51-item measure of restraint, disinhibition,
      and hunger subscales, with the newer 16-item Weight-Related Eating Questionnaire
      (WREQ) measuring routine and compensatory restraint and external and emotional
      eating. METHODS: Both questionnaires were administered to women with overweight
      or obesity (n = 186, mean +/- SD, age 50 +/- 10.6 y, BMI 34 +/- 4.2 kg/m2) at
      five time points. Completion rates were 100% at baseline and Month 1, 94% at
      Month 3, 83% at Month 6, and 76% at Month 12. Confirmatory factor analysis was
      conducted on baseline WREQ data and correlations were calculated between TFEQ and
      WREQ subscales. Multilevel models evaluated the relationship between each
      subscale and weight change over time. RESULTS: Factor analysis revealed a WREQ
      structure consistent with previous research, and corresponding subscales on the
      TFEQ and WREQ were correlated. Lower baseline TFEQ restraint predicted greater
      weight loss. Across five administrations, TFEQ and WREQ restraint scores were
      positively related to weight loss (p < 0.01) and TFEQ disinhibition and WREQ
      external and emotional eating scores were negatively related (p < 0.001). Thus,
      with one baseline administration, only TFEQ restraint was significantly related
      to weight change, but multiple administrations showed relationships between all
      TFEQ and WREQ subscales and weight change. CONCLUSIONS: The WREQ offers a shorter
      alternative to the TFEQ when repeatedly assessing eating behaviors related to
      weight change.

PMID- 28442338
TI  - Multicentre evaluation of postoperative pain control after 24hours in three
      hospitals of Colombia.
AB  - OBJECTIVE: To determine the intensity of pain in operated patients using a visual
      analogue scale and identify variables associated with lack of pain control in
      three cities in Colombia. METHOD: A cross-sectional study in patients over the
      age of 18 years, between January 1st and September 30th 2014, in 3 clinics in
      Colombia. The intensity of postoperative pain using a visual analogue scale at
      24hours after surgery was recorded. Socio-demographic, clinical and
      pharmacological variables were taken into account. SPSS 22.0 was used for the
      analysis. RESULTS: 460 patients were evaluated, mean age 47.6+/-17.4 years, and
      63.3% were female. The mean pain level was 23.8+/-17.4mm, with 91 (19.8% of
      patients) with moderate or greater pain (i.e., lack of pain control). Tramadol
      was the most used analgesic, followed by dipyrone and diclofenac. 53.0% were
      treated with monotherapy. Compliance with the dosing regimen of the first
      analgesic (OR: 0.53; 95% CI: 0.294 to .988; p=.046) was statistically
      significantly associated with a decreased risk of poorly controlled pain.
      CONCLUSIONS: Pain intensity and the proportion of patients with uncontrolled pain
      at 24hours after surgery show better results than other studies previously
      published in the country. There must be insistence on the administration of
      analgesia within a suitable interval in order to improve pain control.

PMID- 28442339
TI  - Neural evidence for the subliminal processing of facial trustworthiness in
      infancy.
AB  - Face evaluation is thought to play a vital role in human social interactions. One
      prominent aspect is the evaluation of facial signs of trustworthiness, which has
      been shown to occur reliably, rapidly, and without conscious awareness in adults.
      Recent developmental work indicates that the sensitivity to facial
      trustworthiness has early ontogenetic origins as it can already be observed in
      infancy. However, it is unclear whether infants' sensitivity to facial signs of
      trustworthiness relies upon conscious processing of a face or, similar to adults,
      occurs also in response to subliminal faces. To investigate this question, we
      conducted an event-related brain potential (ERP) study, in which we presented 7
      month-old infants with faces varying in trustworthiness. Facial stimuli were
      presented subliminally (below infants' face visibility threshold) for only 50ms
      and then masked by presenting a scrambled face image. Our data revealed that
      infants' ERP responses to subliminally presented faces differed as a function of
      trustworthiness. Specifically, untrustworthy faces elicited an enhanced negative
      slow wave (800-1000ms) at frontal and central electrodes. The current findings
      critically extend prior work by showing that, similar to adults, infants' neural
      detection of facial signs of trustworthiness occurs also in response to
      subliminal face. This supports the view that detecting facial trustworthiness is
      an early developing and automatic process in humans.

PMID- 28442340
TI  - Empathy during consoling touch is modulated by mu-rhythm: An EEG study.
AB  - The aim of the present study was to examine the mechanisms of empathy for pain
      that contribute to consoling touch, a distress-alleviating contact behavior
      carried out by an observer in response to the suffering of a target. We tested
      romantic couples in a paradigm that involves consoling touch and examined the
      attenuation of the mu/alpha rhythm (8-13Hz) in the consoling partner. During the
      task, the toucher either held the consoled partner's right hand (human touch) or
      held onto the armrest of the chair (non-human touch), while the consoled partner
      experienced inflicted pain (pain condition) or did not experience any pain (no
      pain condition). In accordance with our hypotheses, the results revealed an
      interaction between touch and pain at in mu/alpha rhythms in all central sites
      (C3, C4, Cz). Specifically, we found that the toucher's mu suppression was higher
      in the consoling touch condition, i.e., while touching the partner who is in
      pain, compared to the three control conditions. Additionally, we found that in
      the consoling touch condition, mu suppression at electrode C4 of the toucher
      correlated with a measure of situational empathy. Our findings suggest that
      electrophysiological and behavioral measures that have been associated with
      empathy for pain are modulated during consoling touch.

PMID- 28442341
TI  - Impact of a general practitioner-led integrated model of care on the cost of
      potentially preventable diabetes-related hospitalisations.
AB  - AIM: To estimate potential savings for Australia's health care system through the
      implementation of an innovative Beacon model of care for patients with complex
      diabetes. METHODS: A prospective controlled trial was conducted comparing a
      multidisciplinary, community-based, integrated primary-secondary care diabetes
      service with usual care at a hospital diabetes outpatient clinic. We extracted
      patient hospitalisation data from the Queensland Hospital Admitted Patient Data
      Collection and used Australian Refined Diagnosis Related Groups to assign costs
      to potentially preventable hospitalisations for diabetes. RESULTS: 327 patients
      with complex diabetes referred by their general practitioner for specialist
      outpatient care were included in the analysis. The integrated model of care had
      potential for national cost savings of $132.5 million per year. CONCLUSIONS: The
      differences in hospitalisations attributable to better integrated
      primary/secondary care can yield large cost savings. Models such as the Beacon
      are highly relevant to current national health care reform initiatives to improve
      the continuity and efficiency of care for those with complex chronic disease in
      primary care.

PMID- 28442342
TI  - Methionine sulfoxide reductase A protects hepatocytes against acetaminophen
      induced toxicity via regulation of thioredoxin reductase 1 expression.
AB  - Thioredoxin reductase 1 (TXNRD1) is associated with susceptibility to
      acetaminophen (APAP)-induced liver damage. Methionine sulfoxide reductase A
      (MsrA) is an antioxidant and protein repair enzyme that specifically catalyzes
      the reduction of methionine S-sulfoxide residues. We have previously shown that
      MsrA deficiency exacerbates acute liver injury induced by APAP. In this study, we
      used primary hepatocytes to investigate the underlying mechanism of the
      protective effect of MsrA against APAP-induced hepatotoxicity. MsrA gene-deleted
      (MsrA-/-) hepatocytes showed higher susceptibility to APAP-induced cytotoxicity
      than wild-type (MsrA+/+) cells, consistent with our previous in vivo results.
      MsrA deficiency increased APAP-induced glutathione depletion and reactive oxygen
      species production. APAP treatment increased Nrf2 activation more profoundly in
      MsrA-/- than in MsrA+/+ hepatocytes. Basal TXNRD1 levels were significantly
      higher in MsrA-/- than in MsrA+/+ hepatocytes, while TXNRD1 depletion in both
      MsrA-/- and MsrA+/+ cells resulted in increased resistance to APAP-induced
      cytotoxicity. In addition, APAP treatment significantly increased TXNRD1
      expression in MsrA-/- hepatocytes, while no significant change was observed in
      MsrA+/+ cells. Overexpression of MsrA reduced APAP-induced cytotoxicity and
      TXNRD1 expression levels in APAP-treated MsrA-/- hepatocytes. Collectively, our
      results suggest that MsrA protects hepatocytes from APAP-induced cytotoxicity
      through the modulation of TXNRD1 expression.

PMID- 28442343
TI  - Pig has no uncoupling protein 1.
AB  - Brown adipose tissue (BAT) is critical for mammal's survival in the cold
      environment. Uncoupling protein 1 (UCP1) is responsible for the non-shivering
      thermogenesis in the BAT. Pig is important economically as a meat-producing
      livestock. However, whether BAT or more precisely UCP1 protein exists in pig
      remains a controversy. The objective of this study was to ascertain whether pig
      has UCP1 protein. In this study, we used rapid amplification of cDNA ends (RACE)
      technique to obtain the UCP1 mRNA 3' end sequence, confirmed only exons 1 and 2
      of the UCP1 gene are transcribed in the pig. Then we cloned the pig UCP1 gene
      exons 1 and 2, and expressed the UCP1 protein from the truncated pig gene using
      E. coli BL21. We used the expressed pig UCP1 protein as antigen for antibody
      production in a rabbit. We could not detect any UCP1 protein expression in
      different pig adipose tissues by the specific pig UCP1 antibody, while our
      antibody can detect the cloned pig UCP1 as well as the mice adipose UCP1 protein.
      This result shows although exons 1 and 2 of the pig UCP1 gene were transcribed
      but not translated in the pig adipose tissue. Furthermore, we detected no
      uncoupled respiration in the isolated pig adipocytes. Thus, these results
      unequivocally demonstrate that pig has no UCP1 protein. Our results have resolved
      the controversy of whether pigs have the brown adipose tissue.

PMID- 28442344
TI  - miR-221 regulates CD44 in hepatocellular carcinoma through the PI3K-AKT-mTOR
      pathway.
AB  - CD44 and miR-221 are upregulated in hepatocellular carcinoma (HCC) cell lines and
      tumors, however a connection between the two has not been identified. As the
      expression of miR-221 directly correlated with CD44 in HCC cells, we hypothesized
      that miR-221 may directly or indirectly regulate CD44 expression. Inhibition of
      miR-221 with antisense in Sk-Hep-1 or SNU-449 cell lines reduced CD44 protein
      expression while miR-221 mimic increased CD44 protein levels. miR-221 antisense
      did not alter the CD44 mRNA levels in Sk-Hep-1 or SNU-449 cells suggesting that
      regulation of CD44 protein occurs post transcriptionally. To discover miRNAs that
      may be involved in the miR-221 regulation of CD44, we performed miRNA profiling
      in SNU-449 cells treated with anti-miR-221. Several miRNAs were increased with
      miR-221 inhibition including miR-708-5p, a miRNA that targets CD44. As miR-221
      targets several regulators of the PI3K-AKT-mTOR pathway and a link between this
      pathway and CD44 has been previously shown in prostate cancer, we considered miR
      221 regulation of CD44 may be through this pathway. Inhibition of miR-221 reduced
      p-4EBP1, a downstream effector of the PI3K-AKT-mTOR pathway. Likewise, inhibiting
      the PI3K-AKT-mTOR pathway with the ATP-competitive mTOR inhibitor PP242 reduced
      CD44 protein in SNU-423 and SNU-449 cells without altering CD44 mRNA levels.

PMID- 28442345
TI  - Characterization of a recombinant humanized anti-cocaine monoclonal antibody
      produced from multiple clones for the selection of a master cell bank candidate.
AB  - We have generated a humanized anti-cocaine monoclonal antibody (mAb), which is at
      an advanced stage of pre-clinical development. We report here in vitro binding
      affinity studies, and in vivo pharmacokinetic and efficacy studies of the
      recombinant mAb. The overall aim was to characterize the recombinant antibody
      from each of the three highest producing transfected clones and to select one to
      establish a master cell bank. In mAb pharmacokinetic studies, after injection
      with h2E2 (120 mg/kg iv) blood was collected from the tail tip of mice over 28
      days. Antibody concentrations were quantified using ELISA. The h2E2 concentration
      as a function of time was fit using a two-compartment pharmacokinetic model. To
      test in vivo efficacy, mice were injected with h2E2 (120 mg/kg iv), then one hour
      later injected with an equimolar dose of cocaine. Blood and brain were collected
      5 min after cocaine administration. Cocaine concentrations were quantified using
      LC/MS. The affinity of the antibody for cocaine was determined using a [3H]
      cocaine binding assay. All three antibodies had long elimination half-lives, 2-5
      nM Kd for cocaine, and prevented cocaine's entry into the brain by sequestering
      it in the plasma. Pharmacokinetic and radioligand binding assays supported
      designation of the highest producing clone 85 as the master cell bank candidate.
      Overall, the recombinant h2E2 showed favorable binding properties,
      pharmacokinetics, and in vivo efficacy.

PMID- 28442346
TI  - Identification of enzymes involved in the mevalonate pathway of Flavobacterium
      johnsoniae.
AB  - The mevalonate pathway is prevalent in eukaryotes, archaea, and a limited number
      of bacteria. This pathway yields the fundamental precursors for isoprenoid
      biosynthesis, i.e., isopentenyl diphosphate and dimethylally diphosphate. In the
      downstream part of the general eukaryote-type mevalonate pathway, mevalonate is
      converted into isopentenyl diphosphate by the sequential actions of mevalonate
      kinase, phosphomevalonate kinase, and diphosphomevalonte decarboxylase, while a
      partial lack of the putative genes of these enzymes is sometimes observed in
      archaeal and bacterial genomes. The absence of these genes has led to the recent
      discovery of modified mevalonate pathways. Therefore, we decided to investigate
      the mevalonate pathway of Flavobacterium johnsoniae, a bacterium of the phylum
      Bacteroidetes, which is reported to lack the genes of mevalonate kinase and
      phosphomevalonate kinase. This study provides proof of the existence of the
      general mevalonate pathway in F. johnsoniae, although the pathway involves the
      kinases that are distantly related to the known enzymes.

PMID- 28442347
TI  - Chronic mitochondrial calcium elevation suppresses leaf senescence.
AB  - Mitochondria Ca2+ overload has long been recognized as a cell death trigger.
      Unexpectedly, we demonstrated a signaling complex composed of Calmodulin (CaM),
      Arabidopsis thaliana Bcl-2-associated athanogene 5 (AtBAG5) and Heat-shock
      cognate 70 protein (Hsc70) within Arabidopsis thaliana mitochondria which
      transduces mitochondria Ca2+ elevations to suppress leaf senescence. Gain- and
      loss-of-function AtBAG5 mutant plants revealed that, mitochondria Ca2+ elevation
      significantly increase chlorophyll retention and decrease H2O2 level in dark
      induced leaf senescence assay. Based on our findings, we proposed a molecular
      mechanism in which chronic mitochondria Ca2+ elevation reduced ROS levels and
      thus inhibits leaf senescence.

PMID- 28442348
TI  - Upregulation of neurotrophins by S 47445, a novel positive allosteric modulator
      of AMPA receptors in aged rats.
AB  - At molecular levels, it has been shown that aging is associated with alterations
      in neuroplastic mechanisms. In this study, it was examined if the altered
      expression of neurotrophins observed in aged rats could be corrected by a chronic
      treatment with S 47445 (1-3-10mg/kg, p.o.), a novel selective positive allosteric
      modulator of the AMPA receptors. Both the mRNA and the protein levels of the
      neurotrophins Bdnf, NT-3 and Ngf were specifically measured in the prefrontal
      cortex and hippocampus (ventral and dorsal) of aged rats. It was found that 2
      week-treatment with S 47445 corrected the age-related deficits of these
      neurotrophins and/or positively modulated their expression in comparison to
      vehicle aged rats in the range of procognitive and antidepressant active doses in
      rodents. Collectively, the ability of S 47445 to modulate various neurotrophins
      demonstrated its neurotrophic properties in two major brain structures involved
      in cognition and mood regulation suggesting its therapeutic potential for
      improving several diseases such as Alzheimer's disease and/or Major Depressive
      Disorders.

PMID- 28442349
TI  - Perinatal programming of the orexinergic (hypocretinergic) system in hypothalamus
      and anterior pituitary by testosterone.
AB  - Orexins A/B derived from hypothalamic prepro-orexin (PPO) are agonists for orexin
      receptors 1 (OX1) and 2 (OX2). Previously, we showed clear sex differences in the
      hypothalamic-pituitary-gonadal orexinergic system in adult rodents. Here, we
      studied the effect of sexual brain differentiation on the orexinergic system in
      neuroendocrine structures regulating reproduction. We evaluated: a: proestrous
      and neonatally androgenized female rats; b: adult males, untreated or
      gonadectomized in adulthood and injected with oil or estradiol and progesterone
      (E2/P4); c: control and demasculinized males (perinatally treated with flutamide
      and later castration) injected either with oil or E2/P4 in adulthood. Rats were
      sacrificed at 12:00 and 18:00h; blood samples and brains were collected. Hormones
      were measured using radioimmunoassay. PPO, OX1 and OX2 mRNAs were quantified by
      qPCR in medial basal hypothalamus, anterior hypothalamus, adenohypophysis, and
      cortex. Western blots for OX1 were done in the same structures. In normal
      females, gonadotropins surged at 18:00h coinciding with significant elevations of
      PPO, OX1 and OX2 mRNAs and OX1 protein in hypothalamus and pituitary; no
      increases were observed at noon. Afternoon changes were absent in masculinized
      females. Demasculinized males when treated with E2/P4 showed high PPO, OX1 and
      OX2 mRNAs and OX1 protein expression in hypothalamus and pituitary at 12:00 and
      18:00h compared vehicle-treated controls. The same steroid treatment was
      ineffective in males with normal brain masculinization. Here we show that
      neonatal testosterone shapes the sexual differences in the hypothalamic-pituitary
      orexinergic system in synchronicity to establishing the brain sex differences of
      the reproductive axis. The female brain controls gonadotropin surges and
      concurrent elevations of all studied components of the orexinergic system,
      suggesting its participation as a possible link between food intake, behavior and
      hormonal control of reproduction.

PMID- 28442350
TI  - Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and
      inhibits apoptosis in breast cancer cells.
AB  - BACKGROUND: Visfatin is a novel adipokine and proinflammatory cytokine which is
      implicated in breast cancer progression. The exact proliferative and anti
      apoptotic mechanisms of visfatin are still under debate. In this study, the
      effect of extracellular visfatin on proliferation and apoptosis of breast cancer
      cells were investigated considering key regulatory molecules in these procedures.
      METHODS: BrdU (Bromodeoxyuridine) experiment was used to assess cell
      proliferation in response to visfatin treatment. Cell viability and apoptosis
      were assessed using MTT assay and flowcytometry, respectively. Phosphorylation
      levels of AKT and ERK1/2 as well as survivin levels and Poly ADP ribose
      polymerase (PARP) cleavage were investigated by western blot analysis. RESULTS:
      Visfatin induced proliferation of MCF-7 and MDA-MB-231 cells, an effect that was
      repressed by using AKT and ERK1/2 inhibitors, indicating involvement of these two
      signaling pathways in the proliferative effect of visfatin. Similarly,
      phosphorylation of AKT and ERK1/2 were elevated by visfatin treatment. On the
      other hand, visfatin improved cell viability and prevented TNF-alpha-induced
      apoptosis as well as PARP cleavage. Visfatin also exerted a protective effect on
      survivin. CONCLUSION: The results of this study suggest that visfatin induces
      breast cancer cell proliferation through AKT/PI3K and ERK/MAPK activation and
      protects against apoptosis in these cells. Thus increased visfatin levels may
      augment breast cancer development and attenuate treatment efficiency in breast
      cancer patients.

PMID- 28442351
TI  - Major depressive disorder mediates accelerated aging in rats subjected to chronic
      mild stress.
AB  - Major depressive disorder (MDD) has a complex etiology and is characterized by a
      change in mood and psychophysiological state. MDD has been shown to mediate
      accelerated biological aging in patients, although the underlying mechanism is
      not well understood. In the present study, we used a chronic mild stress (CMS)
      paradigm to induce anhedonia, one of the main symptoms of MDD. CMS induced
      depression-like symptoms in rats, including reduced sucrose preference and
      increased immobility time in the forced swim test. Moreover, stressed rats
      travelled a shorter total distance, had fewer grid line crossings, and spent less
      time in the outer zone in the open field test than controls. CMS altered the
      levels of 5-hydroxytryptophan, dopamine, and corticosterone in the serum and
      hippocampus (P<0.05); these rats also exhibited impaired liver function,
      decreased telomerase activity, and telomere shortening, which was associated with
      increased oxidative damage along with decreased superoxide dismutase and
      glutathione reductase activities. Mitochondria in CMS-treated rats showed
      ultrastructural damage as well as reduced DNA content and integrity. These
      findings provide physiological and cellular evidence that the MDD can mediate
      accelerated aging in rats.

PMID- 28442352
TI  - The effect of regulatory mode on procrastination: Bi-stable parahippocampus
      connectivity with dorsal anterior cingulate and anterior prefrontal cortex.
AB  - Previous research has elucidated that procrastination can be influenced by
      regulatory mode orientations. However, the neural mechanism of regulatory modes
      affecting procrastination is not well understood. To address this question, we
      employed resting-state functional magnetic resonance imaging (RS-fMRI) to test
      the influence of two regulatory modes (assessment and locomotion) on
      procrastination. The behavioral results showed that procrastination was
      positively correlated with assessment orientation but negatively correlated with
      locomotion orientation. Neuroimaging results indicated that the functional
      connectivity between parahippocampal cortex (PHC) and dorsal anterior cingulate
      (dACC) was negatively correlated with assessment scores, while the functional
      connectivity between anterior prefrontal cortex (aPFC) and parahippocampal cortex
      (PHC) was negatively correlated with locomotion scores. Critically, mediation
      analysis showed that the different effects of two distinct regulatory modes on
      procrastination were mediated by PHC-dACC and aPFC-PHC functional connectivity
      respectively. These results suggested that people's procrastination could be
      predicted by regulatory mode orientations, which is mediated by PHC connectivity
      with dACC and aPFC respectively. The present study extends our knowledge on
      procrastination and provides neural mechanism for understanding the link between
      regulatory mode orientations and procrastination.

PMID- 28442353
TI  - Facebook usage on smartphones and gray matter volume of the nucleus accumbens.
AB  - A recent study has implicated the nucleus accumbens of the ventral striatum in
      explaining why online-users spend time on the social network platform Facebook.
      Here, higher activity of the nucleus accumbens was associated with gaining
      reputation on social media. In the present study, we touched a related research
      field. We recorded the actual Facebook usage of N=62 participants on their
      smartphones over the course of five weeks and correlated summary measures of
      Facebook use with gray matter volume of the nucleus accumbens. It appeared, that
      in particular higher daily frequency of checking Facebook on the smartphone was
      robustly linked with smaller gray matter volumes of the nucleus accumbens. The
      present study gives additional support for the rewarding aspects of Facebook
      usage. Moreover, it shows the feasibility to include real life behavior variables
      in human neuroscientific research.

PMID- 28442354
TI  - The influence of stress on neuroinflammation and alterations in brain structure
      and function in major depressive disorder.
AB  - Major depressive disorder (MDD) is a condition which has often been associated
      with chronic stress. The sympathetic nervous system is continuously activated
      without the normal counteraction of the parasympathetic nervous system under the
      influence of chronic stress. As a result, epinephrine and norepinephrine levels
      are increased, and acetylcholine levels are decreased, which in turn can increase
      the levels of pro-inflammatory cytokines. Peripheral inflammatory responses can
      access the brain, with neuroinflammation contributing to the increase in
      neurotoxic kynurenine pathway metabolites such as 3-hydroxykynurenine, 3
      hydroxyanthranilic acid and quinolinic acid, and decrease in neuroprotective
      metabolites such as kynurenic acid. Pro-inflammatory cytokines can also exert
      direct neurotoxic effects on specific brain regions. Previous imaging studies
      have reported associations between pro-inflammatory states and alterations in
      brain regions involved in emotional regulation, including the hippocampus,
      amygdala and anterior cingulate cortex. Alterations in structure and function of
      such brain areas due to the neurotoxic effects of increased inflammation may be
      associated with the pathophysiology of depression. This review focuses the
      influence of stress on neuroinflammation which may cause alterations in brain
      structure and function in MDD.

PMID- 28442356
TI  - Unbiased stereological analysis of the fate of oligodendrocyte progenitor cells
      in the adult mouse brain and effect of reference memory training.
AB  - Oligodendrocyte progenitor cells (OPCs) are glial cells that differentiate into
      myelinating oligodendrocytes during early stages of post-natal life. However,
      OPCs persist beyond developmental myelination and represent an important
      population of cycling cells in the gray and white matter of the adult brain.
      Here, we used unbiased systematic stereological analysis to determine the total
      number of OPCs in the neocortex and corpus callosum of the adult mouse. We found
      that the ratio of OPCs to neurons is of 1:10 in the adult neocortex. Likewise,
      the ratio of OPCs to oligodendrocytes is of 1:1 in the cortex and 1:7 in the
      corpus callosum. We also used BrdU labeling and the NG2-CreERTM:EYFP reporter
      mouse to determine the proportion of proliferating adult OPCs and their fate. We
      show that OPCs continue to differentiate into oligodendrocytes in adulthood, with
      white matter OPCs being more likely to differentiate into an oligodendrocyte
      phenotype than gray matter OPCs. The differentiation of OPCs into an
      oligodendrocyte phenotype can occur either directly from a spontaneous
      differentiation by an OPC or following OPC cell division. We also provide
      evidence for the neuronal differentiation of adult OPCs in the cortical gray
      matter. Although activity-dependent neural network activity has been hypothesized
      to serve as a modulator of OPC proliferation and differentiation, we found that
      reference memory training did not affect the proportion of proliferating and
      differentiated OPCs in the adult mouse brain.

PMID- 28442355
TI  - Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type
      mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice.
AB  - Muscarinic M1/M4 receptor stimulation can reduce abuse-related effects of cocaine
      and may represent avenues for treating cocaine addiction. Muscarinic antagonists
      can mimic and enhance effects of cocaine, including discriminative stimulus (SD)
      effects, but the receptor subtypes mediating those effects are not known. A
      better understanding of the complex cocaine/muscarinic interactions is needed to
      evaluate and develop potential muscarinic-based medications. Here, knockout mice
      lacking M1, M2, or M4 receptors (M1-/-, M2-/-, M4-/-), as well as control wild
      type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg
      cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity
      (scopolamine), or preferential affinity at the M1, M2, or M4 subtype
      (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested
      alone and in combination with cocaine. In intact animals, antagonists with high
      affinity at M1/M4 receptors partially substituted for cocaine and increased the
      SD effect of cocaine, while M2-preferring antagonists did not substitute, and
      reduced the SD effect of cocaine. The cocaine-like effects of scopolamine were
      absent in M1-/- mice. The cocaine SD attenuating effects of methoctramine were
      absent in M2-/- mice and almost absent in M1-/- mice. The findings indicate that
      the cocaine-like SD effects of muscarinic antagonists are primarily mediated
      through M1 receptors, with a minor contribution of M4 receptors. The data also
      support our previous findings that stimulation of M1 receptors and M4 receptors
      can each attenuate the SD effect of cocaine, and show that this can also be
      achieved by blocking M2 autoreceptors, likely via increased acetylcholine
      release.

PMID- 28442357
TI  - dl-3-n-butylphthalide promotes neuroplasticity and motor recovery in stroke rats.
AB  - BACKGROUNDS AND AIMS: Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a
      functional recovery in animal models of cerebral ischemia, vascular dementia, and
      Alzheimer's disease. In this study, we investigated the effect of dl-NBP on
      axonal growth, neurogenesis and behavioral performances in rats with cerebral
      ischemia. METHODS: Focal cerebral ischemia in rats was produced by intracerebral
      injection of endothelin-1. Starting from postoperative day 7, the experimental
      rats were administered 70mg/kg dl-NBP by oral gavage for two weeks. Biotinylated
      dextran amine (BDA) was injected into the contralateral sensorimotor cortex on
      day 14 after ischemia to trace the sprouting of corticospinal tract (CST) fibers
      into the denervated cervical spinal cord. The expressions of Nogo-A, Nogo-R, Rho
      A, and ROCK in the perilesional cortex, the expressions of BDA, PSD-95, and
      vGlut1 in the denervated spinal cord, 5-bromo-20-deoxyuridine (BrdU)/DCX-positive
      cells in the subventricular zone (SVZ) of the injured hemisphere were detected by
      immunofluorescence. The rats' behavioral abilities were measured on postoperative
      days 30-32 in the beam-walking, cylinder and sticky label tests. RESULTS: dl-NBP
      treatment significantly increased the number and length of crossing CST fibers,
      enhanced significantly the expression levels of synapse-associated proteins
      including PSD95 and VGlut-1 in the denervated cervical spinal cord, elevated the
      number of BrdU+/DCX+ cells in SVZ, and reduced markedly those of Rho-A+, ROCK+,
      Nogo-A+ and Nogo-R+ cells in perilesional cortex. In addition, dl-NBP improved
      the behavioral performance of the ischemic rats. CONCLUSION: dl-NBP enhanced the
      behavioral recovery after cerebral ischemia in rats, possibly by increasing
      axonal growth and neurogenesis.

PMID- 28442358
TI  - An oscillopathic approach to developmental dyslexia: From genes to speech
      processing.
AB  - Developmental dyslexia is a heterogeneous condition entailing problems with
      reading and spelling. Several genes have been linked or associated to the
      disease, many of which contribute to the development and function of brain areas
      important for auditory and phonological processing. Nonetheless, a clear link
      between genes, the brain, and the symptoms of dyslexia is still pending. The goal
      of this paper is contributing to bridge this gap. With this aim, we have focused
      on how the dyslexic brain fails to process speech sounds and reading cues. We
      have adopted an oscillatory perspective, according to which dyslexia may result
      from a deficient integration of different brain rhythms during reading/spellings
      tasks. Moreover, we show that some candidate genes for this condition are related
      to brain rhythms. This fresh approach is expected to provide a better
      understanding of the aetiology and the clinical presentation of developmental
      dyslexia, but also to achieve an earlier and more accurate diagnosis of the
      disease.

PMID- 28442359
TI  - EMG biofeedback training in adult attention-deficit/hyperactivity disorder: An
      active (control) training?
AB  - OBJECTIVE: The present study aimed at revealing neurophysiological effects
      induced by electromyography (EMG) based biofeedback, considered as a semi-active
      control condition in neurofeedback studies, in adult attention
      deficit/hyperactivity disorder (ADHD) patients. METHODS: 20 adult ADHD patients
      trained their muscle activity in the left and right supraspinatus muscle over the
      course of 30 EMG biofeedback sessions. Changes induced by the EMG feedback were
      evaluated at a clinical and neurophysiological level; additionally, the relation
      between changes in EEG activity recorded at the vertex over the training course
      and changes of symptom severity over the treatment course were assessed in order
      to investigate the mechanisms underlying clinical effects of EMG biofeedback.
      RESULTS: Participants showed significant behavioral improvements on a self-rating
      scale. There was a significant increase in alpha power, but no significant
      changes in the delta frequency range; changes in the theta and beta frequency
      range were not significant after adjustment for multiple comparisons. No
      statistically significant correlation was found between changes in EEG frequency
      bands and changes in ADHD symptoms. CONCLUSIONS: The current results assessed by
      means of a single-electrode EEG constitute a starting point regarding a clearer
      understanding of mechanisms underlying clinical effects of EMG biofeedback.
      Although we did not reveal systematic effects induced by EMG feedback on brain
      activity it remains an open question whether EMG biofeedback induces changes in
      brain regions or parameters we did not gather in the present study (e.g. motor
      cortex).

PMID- 28442360
TI  - The OXTR gene, implicit learning and social processing: Does empathy evolve from
      perceptual skills for details?
AB  - Oxytocin is an important messenger in the brain that has been linked to a variety
      of social functions in pharmacological studies. Besides, functional genetic
      variations on the oxytocin receptor gene have been repeatedly associated with
      social processing and functioning. Despite this knowledge, there are very few
      studies investigating the mechanisms that may explain the link between oxytocin
      and social functions. In the endeavor to fill this gap in the literature, the
      current study searches for associations between the prominent rs2268498
      polymorphism on the oxytocin receptor gene and participants' ability to perceive
      and store implicit social information, which is a fundamental function in social
      information processing. N=121 healthy participants were experimentally tested
      with an implicit learning paradigm, answered questionnaires assessing empathy and
      autistic traits, and were genotyped for the rs2268498 polymorphism. T-allele
      carriers (TT and TC genotypes) exhibited significantly better implicit learning
      performance than carriers of the CC-genotype, and learning performance was
      positively associated with self-reported empathy and negatively with self
      reported autistic traits. Results indicate that differences in implicit
      perception and storing of environmental details while watching social
      interactions could be an important mechanism to explain the association between
      differences in endogenous oxytocin activity and social functioning.

PMID- 28442361
TI  - Neuroprotective effects of astaxanthin in a rat model of spinal cord injury.
AB  - Spinal cord injury (SCI) often leads to constant neurological deficits and long
      term unalterable disability. Apoptosis plays an important role in the initiation
      of the secondary injury cascades leading to progressive tissue damage and
      severely functional deficits after SCI. Although the primary mechanical
      destructive events cannot be reversed, a therapeutic intervention could be
      carried out in order to moderate the secondary injury damage several hours to
      weeks after injury. Astaxanthin (AST) is a strong antioxidant and anti
      inflammatory agents with the potential to render anti-apoptotic and
      neuroprotective effects. In the current study, we examined the therapeutic
      potential of AST on adult rats after severe SCI contusion. Results of BBB scores
      showed that AST improved motor function after SCI compared to control groups.
      Western blot analysis showed reduced expression of Bax and Cleaved-caspase-3
      proteins and increased expression of the Bcl-2 protein in response to AST
      treatment (p<0.05). The histology results also showed that AST considerably
      preserved myelinated white matter and the number of motor neurons. This study is
      the first to report that AST reduces neuronal apoptosis, diminishes pathological
      tissue damage and improves functional recovery after SCI. The observed prominent
      neuroprotective effects, introduces AST as a promising therapy for SCI.

PMID- 28442362
TI  - Blockade of muscarinic acetylcholine receptors in the ventral tegmental area
      blocks the acquisition of reward-related learning.
AB  - In the present study we investigated whether stimulation of muscarinic
      acetylcholine (mACh) receptors in the ventral tegmental area (VTA) plays a role
      in the acquisition of food-based conditioned approach learning. Rats were exposed
      to 3 (in Experiment 1) or 7 (in Experiment 2) conditioning sessions in which 30,
      randomly presented light (CS) presentations were paired with delivery of food
      pellets (US), followed by one session with no light or food and finally one CS
      only test session with only light stimulus presentations. Bilateral
      microinjections of scopolamine (a mACh receptor antagonist) were made either
      prior to each conditioning session (Experiment 1; to test effects on acquisition)
      or prior to the CS-only test (Experiment 2; to test effects on performance of the
      learned response). Scopolamine produced a dose-related significant reduction in
      the acquisition of conditioned approach but had no effect on its performance.
      These results suggest that mACh receptor stimulation in the VTA plays a necessary
      role in the acquisition of reward-related learning.

PMID- 28442363
TI  - The global expression profiling in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is the dominant subtype of esophageal
      cancer worldwide. This study aimed to explore the aberrant global expression
      profiling and construct regulatory network in ESCC for understanding
      tumorigenesis of ESCC. The expression pattern of long non-coding RNA (lncRNA),
      microRNA (miRNA) and mRNA was measured by RNA-sequencing in ESCC. Differentially
      expressed lncRNAs/miRNAs/mRNAs (DELs/DEMs/DEMIs) were identified in ESCC. DEMIs
      DEMs network was constructed; hsa-miR-424-5p and hsa-miR-450b-5p were the hub
      miRNAs in the network, which negatively regulated 19 and 17 DEMs. DEMs targeted
      by DEMIs were significantly enriched in MAPK signaling pathway, pathways in
      cancer and focal adhesion signaling pathway. The expression of candidate DEMs and
      DEMIs in ESCC were validated through quantitative real-time polymerase chain
      reaction and microarray expression profiling analyses, and the results were
      generally consistent with our bioinformatics analysis. Our results might provide
      useful information for exploring the tumorigenesis mechanism and potentially
      therapeutic targets in ESCC.

PMID- 28442364
TI  - Effects of repeated cocaine exposure and withdrawal on voluntary ethanol
      drinking, and the expression of glial glutamate transporters in mesocorticolimbic
      system of P rats.
AB  - Glutamatergic neurotransmission within the brain's reward circuits plays a major
      role in the reinforcing properties of both ethanol and cocaine. Glutamate
      homeostasis is regulated by several glutamate transporters, including glutamate
      transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate
      aspartate transporter (GLAST). Cocaine exposure has been shown to induce a
      dysregulation in glutamate homeostasis and a decrease in the expression of GLT-1
      and xCT in the nucleus accumbens (NAc). In this study, alcohol preferring (P)
      rats were exposed to free-choice of ethanol (15% and 30%) and/or water for five
      weeks. On Week 6, rats were administered (i.p.) cocaine (10 and 20mg/kg) or
      saline for 12 consecutive days. This study tested two groups of rats: the first
      group was euthanized after seven days of repeated cocaine i.p. injection, and the
      second group was deprived from cocaine for five days and euthanized at Day 5
      after cocaine withdrawal. Only repeated cocaine (20mg/kg, i.p.) exposure
      decreased ethanol intake from Day 3 through Day 8. Co-exposure of cocaine and
      ethanol decreased the relative mRNA expression and the expression of GLT-1 in the
      NAc but not in the medial prefrontal cortex (mPFC). Importantly, co-exposure of
      cocaine and ethanol decreased relative expression of xCT in the NAc but not in
      the mPFC. Our findings demonstrated that chronic cocaine exposure affects ethanol
      intake; and ethanol and cocaine co-abuse alters the expression of glial glutamate
      transporters.

PMID- 28442365
TI  - B cell-activating factor regulates the survival of B lymphocytes infected with
      human cytomegalovirus.
AB  - BACKGROUND: Previous studies have suggested that B lymphocytes can be
      polyclonally activated by human cytomegalovirus (HCMV), and individuals infected
      by HCMV exhibit characteristic features of an autoimmunity disease. B cell
      activating factor (BAFF) plays important roles in the survival and
      differentiation of B cells; however, few studies have examined the potential role
      of BAFF on B cells infected by HCMV. METHODS: HCMV virus strain (HCMV AD-169) was
      concentrated by normal methods and used to infect microbead-purified tonsil CD19+
      B cells. Cells and supernatants were collected at the 1st, 3rd, 5th, and 7th day
      of co-culture, respectively. Cellular phenotypes, including expression of BAFF
      and its cognate receptors (BAFF-R, TACI, and BCMA) were detected by flow
      cytometry (FCM); cells apoptosis rates were also examined by FCM; and IgG titers
      in supernatants was detected by ELISA. In parallel, neutralizing anti-BAFF-R
      antibody was applied to observe the effect of BAFF/BAFF-R signaling on apoptosis
      and the IgG secretion ability of B cells stimulated by HCMV. RESULTS: LogTCID50
      of 3rd and 4th generation of HCMV was -3.54 and -3.28, respectively. FCM results
      showed that the purity of CD19+ B cells was >98%. BAFF-R was highly expressed and
      upregulated on HCMV-infected B cells (93.5%-99.3%), compared with B cells prior
      to HCMV infection and uninfected group; while BAFF-R expression gradually
      decreased with time and to the lowest level at 5th day (81%) in the control
      medium-only group. In contrast, expression of TACI and BCMA gradually increased
      during culture in both HCMV-infected and medium-only control B cells.
      Furthermore, the apoptosis rate of HCMV-infected and medium-only control B cells
      did not vary significantly during culture, but IgG secretion ability of HCMV
      infected B cells significantly increased over time while no changes were observed
      with the medium-only control. Importantly, the apoptosis rate of B cells
      significantly increased when BAFF/BAFF-R signal was blocked prior to HCMV
      infection (P<0.05), although no significant changes of IgG levels were observed
      (P>0.05). CONCLUSIONS: BAFF-R was consistently expressed on B cells infected by
      HCMV. Enhancement of BAFF/BAFF-R signaling decreased the apoptosis rate and
      extended the survival of B cells.

PMID- 28442366
TI  - Regulating distal tip cell migration in space and time.
AB  - Gonad morphogenesis in the nematode C. elegans is guided by two leader cells, the
      distal tip cells (DTC). The DTCs migrate along a stereotyped path, executing two
      90 degrees  turns before stopping at the midpoint of the animal. This migratory
      path determines the double-U shape of the adult gonad, therefore, the path taken
      by the DTCs can be inferred from the final shape of the organ. In this review, we
      focus on the mechanism by which the DTC executes the first 90 degrees  turn from
      the ventral to dorsal side of the animal, and how it finds its correct stopping
      place at the midpoint of the animal. We discuss the role of heterochronic genes
      in coordinating DTC migration with larval development, the role of feedback loops
      and miRNA regulation in phenotypic robustness, and the role of RNA binding
      proteins in the cessation of DTC migration.

PMID- 28442367
TI  - D'Arcy Thompson's 'on Growth and form': From soap bubbles to tissue self
      organization.
AB  - Tissues are thought to behave like fluids with a given surface tension.
      Differences in tissue surface tension (TST) have been proposed to trigger cell
      sorting and tissue envelopment. D'Arcy Thompson in his seminal book 'On Growth
      and Form' has introduced this concept of differential TST as a key physical
      mechanism dictating tissue formation and organization within the developing
      organism. Over the past century, many studies have picked up the concept of
      differential TST and analyzed the role and cell biological basis of TST in
      development, underlining the importance and influence of this concept in
      developmental biology.

PMID- 28442368
TI  - Differences between adolescents and adults in the acute effects of PCP and
      ketamine and in sensitization following intermittent administration.
AB  - Adolescence is a phase of development during which many physiological and
      behavioral changes occur, including increased novelty seeking and risk taking. In
      humans, this is reflected in experimentation with drugs. Research demonstrates
      that drug use that begins during adolescence is more likely to lead to addiction
      than drug use that begins later in life. Despite this, relatively little is known
      of the effects of drugs in adolescence, and differences in response between
      adolescents and adults. PCP and ketamine are popular club drugs, both possessing
      rewarding properties that could lead to escalating use. Drug sensitization (or
      reverse tolerance), which refers to an increase in an effect of a drug following
      repeated use, has been linked with the development of drug cravings that is a
      hallmark of addiction. The current work investigated the acute response and the
      development of sensitization to PCP and ketamine in adolescent and adult rats.
      Periadolescent Sprague-Dawley rats (30days or 38days of age), and young adults
      (60days of age) received PCP (6mg/kg IP) or ketamine (20mg/kg IP) once every
      three days, for a total of five drug injections. Adolescents and adults showed a
      stimulant response to the first injection of either drug, however the response
      was considerably greater in the youngest adolescents and lowest in the adults.
      With repeated administration, adults showed a robust escalation in activity that
      was indicative of the development of sensitization. Adolescents showed a flatter
      trajectory, with similar high levels of activity following an acute treatment and
      after five drug treatments. The results demonstrate important distinctions
      between adolescents and adults in the acute and repeated effects of PCP and
      ketamine.

PMID- 28442369
TI  - Further evaluation of the potential anxiolytic activity of imidazo[1,5
      a][1,4]diazepin agents selective for alpha2/3-containing GABAA receptors.
AB  - Positive allosteric modulators of GABAA receptors transduce a host of beneficial
      effects including anxiolytic actions. We have recently shown that bioavailability
      and anxiolytic-like activity can be improved by eliminating the ester
      functionality in imidazo[1,5-a][1,4]diazepines. In the present series of
      experiments, we further substantiate the value of heterocyle replacement of the
      ester for potential treatment of anxiety. None of three esters was active in a
      Vogel conflict test in rats that detects anxiolytic drugs like diazepam.
      Compounds 7 and 8, ester bioisosters, were selective for alpha 2 and 3 over alpha
      1-containing GABAA receptors but also had modest efficacy at GABAA alpha 5
      containing receptors. Compound 7 was efficacious and potent in this anxiolytic
      detecting assay without affecting non-punished responding. The efficacies of the
      esters and of compound 7 were predicted from their efficacies as anticonvulsants
      against the GABAA antagonist pentylenetetrazole (PTZ). In contrast, the related
      structural analog, compound 8, did not produce anxiolytic-like effects in rats
      despite anticonvulsant efficacy. These data thus support the following
      conclusions: 1) ancillary pharmacological actions of compound 8 might be
      responsible for its lack of anxiolytic-like efficacy despite its efficacy as an
      anticonvulsant 2) esters of imidazo[1,5-a][1,4]diazepines do not demonstrate
      anxiolytic-like effects in rats due to their low bioavailability and 3)
      replacement of the ester function with suitable heterocycles markedly improves
      bioavailability and engenders molecules with the opportunity to have potent and
      efficacious effects in vivo that correspond to human anxiolytic actions.

PMID- 28442371
TI  - DynaMiTES - A dynamic cell culture platform for in vitro drug testing PART 1 -
      Engineering of microfluidic system and technical simulations.
AB  - Conventional safety and efficacy test models, such as animal experiments or
      static in vitro cell culture models, can often not reliably predict the most
      promising drug candidates. Therefore, a novel microfluidic cell culture platform,
      called Dynamic Micro Tissue Engineering System (DynaMiTES), was designed to allow
      online analysis of drugs permeating through barrier forming tissues under dynamic
      conditions combined with monitoring of the transepithelial electrical resistance
      (TEER) by electrodes optimized for homogeneous current distribution. A variety of
      pre-cultivated cell culture inserts can be integrated and exposed to well
      controlled dynamic micro flow conditions, resulting in a tightly regulated
      exposure of the cells to tested drugs, drug formulations and shear forces. With
      these qualities, the new system can provide more relevant information compared to
      static measurements. As a first in vitro model, a three-dimensional hemicornea
      construct consisting of human keratocytes (HCK-Ca) and epithelial cells (HCE-T)
      was successfully tested in the DynaMiTES. Thereby, we were able to demonstrate
      the functionality and cell compatibility of this new organ on chip test platform.
      The modular design of the DynaMiTES allows fast adaptation suitable for the
      investigation of drug permeation through other important cellular barriers.

PMID- 28442370
TI  - Modulation of drug choice by extended drug access and withdrawal in rhesus
      monkeys: Implications for negative reinforcement as a driver of addiction and
      target for medications development.
AB  - Chronic drug exposure is hypothesized to recruit negative reinforcement processes
      that increase the magnitude and alter the mechanisms of drug reinforcement.
      Candidate substrates of negative reinforcement include increased signaling via
      stress-related neurotransmitters such as corticotropin releasing factor (CRF,
      acting at CRF receptors) or dynorphin (acting at kappa opioid receptors) and/or
      decreased signaling via reward-related neurotransmitters such as dopamine.
      Determinants of drug reinforcement can be examined with choice procedures, in
      which subjects choose between a drug of interest (e.g. heroin or cocaine) and a
      non-drug alternative reinforcer (e.g. food). This review summarizes evidence
      collected from studies of drug choice in rhesus monkeys to address the negative
      reinforcement hypothesis. In monkeys choosing between heroin and food, chronic
      heroin exposure and subsequent withdrawal produces a robust increase in heroin
      choice. This withdrawal-associated increase in heroin choice is blocked by
      morphine and by other mu opioid agonists used to treat opioid use disorder
      (methadone, buprenorphine); however, withdrawal-associated increases in heroin
      choice are not reliably blocked by antagonists of CRF or kappa opioid receptors
      or by an indirect dopamine agonist. In monkeys choosing between cocaine and food,
      chronic cocaine exposure and withdrawal fail to increase cocaine choice or alter
      sensitivity of cocaine choice to treatment with candidate therapeutics including
      an indirect dopamine agonist and a kappa opioid receptor antagonist. These
      results support a role for negative reinforcement in self-administration of
      heroin but not cocaine. The constellation of neurobiological changes that
      constitutes the negative reinforcing stimulus in opioid-dependent rhesus monkeys
      remains to be determined.

PMID- 28442372
TI  - Long-term release and stability of pharmaceutical proteins delivered from solid
      lipid implants.
AB  - Solid lipid implants (SLIs) prepared by twin-screw (tsc) extrusion represent a
      promising technology platform for the sustained release of pharmaceutical
      proteins. In this work, we report on two aspects, long-term release and stability
      of released protein. First, SLIs were produced by tsc-extrusion containing the
      low melting triglyceride H12 and the high melting triglyceride Dynasan D118. Two
      different proteins available in a freeze-dried matrix containing hydroxypropyl
      beta-cyclodextrine (HP-beta-CD) were incorporated into the lipid matrix: a
      monoclonal antibody (mAb) from the IgG1 class and the fab-fragment Ranibizumab
      (Lucentis(r)). SLIs, composed of 10% protein lyophilizate and both triglycerides,
      were extruded at 35 degrees C and 40rpm. Sustained release of both proteins was
      observed in a sustained manner for approximately 120days. Protein load per
      implant was increased by three different approaches resulting in a protein load
      of 3.00mg per implant without affecting the release profiles. The incubation
      medium containing the released protein was collected, concentrated and analyzed
      including liquid chromatography (SE-HPLC, IEX, HIC), electrophoresis (SDS-PAGE,
      on-chip gel electrophoresis) and FT-IR spectroscopy. The mAb showed a monomer
      loss of up to 7% (SE-HPLC) and IEX analysis revealed the formation of 16% acidic
      subspecies after 18weeks. FT-IR spectra of mAb indicated the formation of random
      coil structures towards the end of the release study. Ranibizumab was mainly
      released in its monomeric form (>95%), and approximately 5% hydrophobic
      subspecies were formed after 18weeks of release. FT-IR analysis revealed no
      changes in secondary structure. The release and stability profiles of both
      proteins underline the potential of SLIs as a delivery system. SLIs provide a
      promising platform for applications where really long-term release is needed, for
      example for intraocular delivery of anti-vascular endothelial growth factor
      (VEGF) drugs for age related macular degeneration (AMD).

PMID- 28442373
TI  - Nasal mucociliary transportability of male and female smokers.
AB  - INTRODUCTION: Female smoker's present increased susceptibility to several
      diseases when compared to the opposite gender. However, there are no studies
      showing differences in nasal mucociliary transport behavior between male and
      female smokers. OBJECTIVE: To compare the nasal mucociliary transportability in
      male and female smokers and non-smokers, taking into consideration age,
      anthropometric data, smoking load and pulmonary function. METHODS: The analysis
      included 139 individuals (33 men and 37 women smokers and 32 men and 37 women non
      smokers). All participants answered an initial interview to obtain personal data
      and smoking load. Anthropometric data and carbon monoxide in the exhaled air were
      assessed. Individuals also performed pulmonary function test and Saccharin
      Transit Time test. To compare saccharin transit time values between men and
      women, smokers and non-smokers, stratification of all independent variables was
      performed (sociodemographic, smoking and respiratory variables) into two
      categories: below and above the median values. RESULTS: There was no difference
      between men and women, smokers and non-smokers, regarding nasal mucociliary
      transportability. Significant differences were only observed between non-smokers.
      Among those with less forced vital capacity values (<97.37% of predicted), women
      presented mucociliary transport faster than men. Moreover, it was observed
      influence of BMI and COex (women smokers), FCV and FEV1 (men non-smokers) and
      FEF25-75% (women non-smokers) on saccharin transit time values. CONCLUSION: Based
      on the findings of this study, nasal mucociliary transport in male and female
      adult smokers, apparently healthy, are similar.

PMID- 28442374
TI  - Peritonsillar and deep neck infections: a review of 330 cases.
AB  - INTRODUCTION: Deep neck infections are defined as suppurative infectious
      processes of deep visceral spaces of the neck. OBJECTIVE: The aim of this study
      is to review different factors that may influence peritonsillar and deep neck
      infections and may play a role as bad prognosis predictors. METHODS: We present a
      retrospective study of 330 patients with deep neck infections and peritonsillar
      infections who were admitted between January 2005 and December 2015 in a tertiary
      referral hospital. Statistical analysis of comorbidities, diagnostic and
      therapeutic aspects was performed with Excel and SPSS. RESULTS: There has been an
      increase in incidence of peritonsilar and deep neck infections. Systemic
      comorbidities such as diabetes or hepatopathy are bad prognosis factors. The most
      common pathogen was S. viridans (32.1% of positive cultures). 100% of the
      patients received antibiotics and corticosteroids, 74.24% needed surgical
      treatment. The most common complications were mediastinitis (1.2%) and airway
      obstruction (0.9%). CONCLUSION: Systemic comorbidities are bad prognosis
      predictors. Nowadays mortality has decreased thanks to multidisciplinary
      attention and improvements in diagnosis and treatment.

PMID- 28442375
TI  - Implication of hyperoxaluria on osteopontin and ER stress mediated apoptosis in
      renal tissue of rats.
AB  - Hyperoxaluria is a stress that leads to calcium oxalate crystal deposition which
      further causes inflammation and renal cell necroptosis. Many studies have linked
      osteopontin expression with apoptosis and inflammation but so far its association
      with apoptosis with regard to hyperoxaluria is undiscovered. Moreover, a recent
      report has suggested that osteopontin induces endoplasmic reticulum stress and
      subsequently apoptosis in myocytes. In this study, the impact of hyperoxaluria on
      the modulation of osteopontin expression and endoplasmic reticulum (ER) stress
      mediated apoptosis in rats is explored. Hyperoxaluria was induced in rats by
      three different doses viz. ethylene glycol alone, ethylene glycol and ammonium
      chloride together and third group were fed with hydroxyl-l-proline. After
      hyperoxaluria induction rats were sacrificed and renal tissue was analysed for
      crystal depositions, osteopontin expression, inflammation, ER stress and
      subsequent unfolded protein response intermediates (UPR). Altered
      histoarchitecture of renal tissue and elevated levels of reactive oxygen species
      (ROS) along with the presence of calcium oxalate crystals were observed in the
      hyperoxaluric groups. As expected, inflammation and apoptosis was significantly
      high in all hyperoxaluria groups. Osteopontin expression showed significant up
      regulation following hyperoxaluria. Further, a similar trend between expression
      of osteopontin and elevated ER stress level was observed. Moreover, UPR
      intermediates expression was also concurrent with osteopontin levels. It is
      observed that the extent of calcium oxalate crystal deposition is directly
      associated with the expression of osteopontin, inflammation and ER stress. The
      results advocate possible association of osteopontin with ER stress, thus
      suggesting that the ER could be a new target for developing therapeutic regimes
      for kidney stones.

PMID- 28442376
TI  - Copper sulfate pretreatment prevents mitochondrial electron transport chain
      damage and apoptosis against MPP+-induced neurotoxicity.
AB  - Intrastriatal injection of 1-methyl-4-phenylpyridinium (MPP+) is considered a
      model to reproduce some biochemical alterations observed in Parkinson's disease
      (PD) patients. Among those alterations, inhibition of mitochondrial complex I
      activity, increased free radical production and reduced antioxidant responses
      have been reported. Copper (Cu) plays an important role in the metabolism and
      antioxidative responses through its participation as a cofactor in the cytochrome
      c oxidase enzyme (COX), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and
      metallothioneins. We tested the effect of copper sulfate (CuSO4) pretreatment on
      the mitochondrial electron transport chain (METC) in the striatum after MPP+
      toxicity in rats. The results showed that the MPP+ intrastriatal injection
      reduced mitochondrial complex I, II, IV and V activities; while 10 MUmol of CuSO4
      pretreatment counteracted this damage. Activities of complexes I, II and IV, were
      coincident with ATP recovery. Moreover, Cu/Zn-SOD activity was reduced as a
      consequence of MPP+ damage; however, copper pre-treatment kept the striatal Cu/Zn
      SOD activity unchanged in MPP+-damaged animals. We observed that MPP+ also
      reduced the metallothionein (MT) content and that CuSO4 pretreatment maintained
      baseline values. CuSO4 pretreatment also reduced the striatal caspase-3 and
      caspase-9 activities that were increased three days after MPP+-induced damage.
      The present study provided evidence that copper pretreatment reduced MPP+-induced
      apoptotic damage, probably through direct action on copper-dependent proteins or
      indirectly on proteins in the apoptotic pathway.

PMID- 28442377
TI  - Zerumbone reduced the inflammatory response of acute lung injury in endotoxin
      treated mice via Akt-NFkappaB pathway.
AB  - Zerumbone, a cyclic eleven-membered sesquiterpene, is the major component of the
      essential oil isolated from the wild ginger, Zingiber zerumbet. There are several
      beneficial pharmacological activities of zerumbone including anti-inflammatory,
      antioxidant, and anticancer activities. Acute lung injury (ALI) is an acute
      pulmonary inflammatory disorder with high morbidity and mortality rate. In
      present study, we aimed to investigate the protective effects and mechanisms of
      zerumbone on endotoxin, lipopolysaccharide (LPS)-induced ALI. Mice were
      pretreated with zerumbone at various concentrations for 30 min followed by
      intratracheal administration of LPS for 6 h. Pretreatment with zerumbone not only
      reduced leukocytes infiltration into the alveolar space but also inhibited lung
      edema in LPS-induced ALI. Decreased secretion of proinflammatory cytokines such
      as TNFalpha and IL-6 caused by LPS were reversed by zerumbone. LPS-induced
      expressions of proinflammatory mediators, iNOS and COX-2, were inhibited by
      zerumbone. In addition, NFkappaB activation and Akt phosphorylation were
      inhibited by zerumbone in LPS-induced ALI. All these results suggested that the
      protective mechanisms of zerumbone on endotoxin-induced ALI were via inhibition
      of Akt-NFkappaB activation.

PMID- 28442378
TI  - Antihyperlipidemic and antiapoptotic potential of zingerone on alcohol induced
      hepatotoxicity in experimental rats.
AB  - The ultimate aim of this present study was to investigate the antihyperlipidemic
      and antiapoptotic potential of zingerone (ZO) on alcohol induced hepatotoxicity
      in experimental rats. Male albino wistar rats were divided in four groups. Groups
      1 and 2 rats received isocaloric glucose and dimethyl sulphoxide (2% DMSO), liver
      toxicity was induced in groups 3 and 4 by supplementing 30% ethanol post orally
      for 60 days. In addition to, groups 2 and 4 received zingerone (20 mg/kg body
      weight in 2% DMSO) daily during the final 30 days of the experimental period.
      Ethanol alone administered rats showed increased levels/activities of plasma
      total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), phospholipids
      (PL), low density lipoproteins (LDL), very low density lipoproteins (VLDL),
      tissue TC, TG, FFA, PL, HMG-CoA reductase, phase I xenobiotic enzymes, collagen
      and fat accumulation, DNA damage and increased Bax, caspase-3 and caspase-9
      expressions and decrease in the levels/activities of plasma high density
      lipoproteins (HDL), lipoprotein lipase (LPL), lecithin cholesterol acyl
      transferase (LCAT), phase II xenobiotic enzymes and a decreased Bcl-2 expression.
      Zingerone supplementation was able to counter and reverse the ethanol induced
      changes in all the above parameters in experimental rats. Together results
      portray zingerone exhibits antihyperlipidemic and antiapoptotic potential on
      alcohol induced hepatotoxicity.

PMID- 28442380
TI  - Incidence and risk factors of symptomatic dry eye disease in Asian Malays from
      the Singapore Malay Eye Study.
AB  - PURPOSE: To evaluate the incidence of symptomatic dry eye disease (SDED) and
      associated risk factors in a well-characterized cohort of ethnic Malays in
      Singapore. METHODS: We included 1682 participants (mean age [SD]: 57 [10]years;
      55.4% female) without SDED from the Singapore Malay Eye Study (SiMES), a
      population-based longitudinal study with baseline examination (SiMES-1) conducted
      between 2004 and 2006, and follow-up examination (SiMES-2) conducted between 2010
      and 2013. SDED was considered to be present if a participant answered "often" or
      "all the time" to any of the six questions from the Salisbury Eye Evaluation
      Study dry eye questionnaire. Age-standardized incidence of SDED was calculated as
      the crude 6-year cumulative incidence standardized to Singapore's population
      census. Gender-stratified multivariable log-binomial regression models were
      utilized to determine the independent risk factors of incident SDED. RESULTS: At
      the 6-year follow-up, 86 of 1682 participants had developed SDED, which was
      equivalent to an age-standardized 6-year incidence of 5.1% (95% CI 4.1-6.4%).
      There were no differences in the incidence of SDED between men and women (P =
      0.9). Multivariable models revealed that presence of glaucoma and poorer self
      rated health were independently associated with incident SDED in men (P = 0.003
      and 0.03, respectively), while contact lens wear (P = 0.002), history of thyroid
      disease (P = 0.03), and having had cataract surgery (P = 0.02) were predictive of
      incident SDED in women. CONCLUSION: One in twenty adult Malays developed SDED
      over a 6-year period. Risk factors for incident SDED were different between men
      and women. Future studies and public health interventions should consider this
      gender-specific difference in risk factors.

PMID- 28442379
TI  - Peripheral membrane associations of matrix metalloproteinases.
AB  - Water soluble matrix metalloproteinases (MMPs) have been regarded as diffusing
      freely in the extracellular matrix. Yet multiple MMPs are also observed at cell
      surfaces. Their membrane-proximal activities include sheddase activities,
      collagenolysis, bacterial killing, and intracellular trafficking reaching as far
      as the nucleus. The catalytic domains of MMP-7 and MMP-12 bind bilayers
      peripherally, each in two different orientations, by presenting positive charges
      and a few hydrophobic groups to the surface. Related peripheral membrane
      associations are predicted for other soluble MMPs. The peripheral membrane
      associations may support pericellular proteolysis and endocytosis. The isolated
      soluble domains of MT1-MMP can also associate with membranes. NMR assays suggest
      transient association of the hemopexin-like domains of MT1-MMP and MMP-12 with
      lipid bilayers. Peripheral association of soluble MMP domains with bilayers or
      heparin sulfate proteoglycans probably concentrates them near the membrane. This
      could increase the probability of forming complexes with membrane-associated
      proteins, such as those targeted for proteolysis. This article is part of a
      Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman.

PMID- 28442381
TI  - Ocular surface alkali injury damages meibomian glands in mice.
AB  - PURPOSE: To examine effects of alkali injury of the ocular surface on meibomian
      gland pathology in mice. METHODS: Three MUL of 1 N NaOH were applied under
      general anesthesia to the right eye of 10-week-old BALB/c (n = 54) mice to
      produce a total ocular surface alkali burn. The meibomian gland morphology was
      examined at days 1, 2, 5, 10, and 20 by stereomicroscopy and non-contact infrared
      meibography. Mice were then sacrificed and eyelids processed for histology with
      hematoxylin-eosin and immunohistochemistry for ELOVL4, PPARgamma, myeloperoxidase
      (a neutrophil marker) and F4/80 macrophage antigen, as well as TUNEL staining.
      Another set of specimens was processed for cryosectioning and Oil red O staining.
      RESULTS: Alkali injury to the ocular surface produced cellular apoptosis,
      infiltration of neutrophils and macrophages, degeneration of the meibomian gland,
      and ductal dilation. Inflammation in and destruction of acunal stricture seemed
      more prominent in the lower eyelid, while duct dilation was more frequently
      observed in the upper eyelid during healing. Surviving acinar cells were labeled
      for ELOVL4 and PPARgamma. Oil red O staining showed that the substance in the
      dilated duct contained predominantly neutral lipid. CONCLUSIONS: Alkali injury to
      the ocular surface results in damage and destruction of the eyelid meibomian
      glands. The pattern of the tissue damage differs between glands of the upper and
      lower eyelids.

PMID- 28442382
TI  - Relationship between sensorimotor peripheral nerve function and indicators of
      cardiovascular autonomic function in older adults from the Health, Aging and Body
      Composition Study.
AB  - BACKGROUND: Age-related peripheral nervous system (PNS) impairments are highly
      prevalent in older adults. Although sensorimotor and cardiovascular autonomic
      function have been shown to be related in persons with diabetes, the nature of
      the relationship in general community-dwelling older adult populations is
      unknown. METHODS: Health, Aging and Body Composition participants (n=2399,
      age=76.5+/-2.9years, 52% women, 38% black) underwent peripheral nerve testing at
      the 2000/01 clinic visit. Nerve conduction amplitude and velocity were measured
      at the peroneal motor nerve. Sensory nerve function was assessed with vibration
      detection threshold and monofilament (1.4-g/10-g) testing at the big toe.
      Symptoms of lower-extremity peripheral neuropathy were collected by self-report.
      Cardiovascular autonomic function indicators included postural hypotension,
      resting heart rate (HR), as well as HR response to and recovery from submaximal
      exercise testing (400m walk). Multivariable modeling adjusted for
      demographic/lifestyle factors, medication use and comorbid conditions. RESULTS:
      In fully adjusted models, poor motor nerve conduction velocity (<40m/s) was
      associated with greater odds of postural hypotension, (OR=1.6, 95% CI: 1.0-2.5),
      while poor motor amplitude (<1mV) was associated with 2.3beats/min (p=0.003)
      higher resting HR. No associations were observed between sensory nerve function
      or symptoms of peripheral neuropathy and indicators of cardiovascular autonomic
      function. CONCLUSIONS: Motor nerve function and indicators of cardiovascular
      autonomic function remained significantly related even after considering many
      potentially shared risk factors. Future studies should investigate common
      underlying processes for developing multiple PNS impairments in older adults.

PMID- 28442383
TI  - Axial Abdominal Imaging after Partial Nephrectomy for T1 Renal Cell Carcinoma
      Surveillance.
AB  - PURPOSE: The overall recurrence rate of T1 renal cell carcinoma is low. We
      evaluated abdominal imaging after partial nephrectomy based on current guidelines
      for T1 renal cell carcinoma surveillance. MATERIALS AND METHODS: We
      retrospectively reviewed the records of patients with T1 renal cell carcinoma who
      underwent partial nephrectomy between 2006 and 2012 followed by abdominal imaging
      at our institution. Primary and secondary outcomes were the incidence and timing,
      respectively, of imaging diagnosed abdominal recurrences. A literature review was
      performed to summarize prior reports of recurrence incidence and timing after
      partial nephrectomy for T1 disease. RESULTS: A total of 160 patients with stage
      T1a and 37 with T1b underwent partial nephrectomy. Seven patients had an
      abdominal recurrence, including 3 with local and distant recurrences, and 4 with
      a metachronous contralateral kidney recurrence. The incidence of abdominal
      recurrence detected by imaging was higher in the T1b than in the T1a group (10.8%
      vs 1.9%, p = 0.024). Although it was not significant, median time to recurrence
      was earlier in T1b vs T1a cases (13 vs 37 months, p = 0.480). In each group
      recurrences developed after 3 years of suggested guideline surveillance. In the
      literature combined with the current study the time to median recurrence for T1b
      vs T1a was 24 vs 29 months (p = 0.226). CONCLUSIONS: Recurrences detected by
      abdominal imaging developed earlier and more frequently in T1b than in T1a cases.
      Future recommendations for surveillance strategies after partial nephrectomy
      should distinguish T1a from T1b with less intense frequency of imaging for T1a. A
      longer period of surveillance should be considered since recurrences can develop
      beyond 3 years.

PMID- 28442384
TI  - Optimal Settings for the Noncontact Holmium:YAG Stone Fragmentation Popcorn
      Technique.
AB  - PURPOSE: The purpose of this study was to evaluate the popcorn technique using a
      wide range of holmium laser settings and fiber sizes in a systematic in vitro
      assessment. MATERIALS AND METHODS: Evaluations were done with 4 artificial stones
      in a collection tube. A fixed ureteroscope was inserted through a ureteral access
      sheath to provide constant irrigation flow and the laser was placed 1 mm from the
      bottom. Combinations of 0.5 to 1.5 J, 10 to 20 and 40 Hz, and long and short
      pulses were tested for 2 and 4 minutes. We used 273 and 365 MUm laser fibers. All
      tests were repeated 3 times. The stones were weighed before and after the
      experiments to evaluate the setting efficiency. Significant predictors of a
      highly efficient technique were assessed. RESULTS: A total of 144 tests were
      performed. Mean starting weight of the stones was 0.23 gm, which was consistent
      among the groups. After the experiment the median weight difference was 0.07 gm
      (range 0.01 to 0.24). When designating a 50% reduction in stone volume as the
      threshold indicating high efficiency, the significant predictors of an efficient
      popcorn technique were a long pulse (OR 2.7, 95% CI 1.05-7.15), a longer duration
      (OR 11.4, 95% CI 3.88-33.29), a small (273 MUm) laser fiber (OR 0.23, 95% CI 0.08
      0.70) and higher power (W) (OR 1.14, 95% CI 1.09-1.20). CONCLUSIONS: Higher
      energy, a longer pulse, frequencies higher than 10 Hz, a longer duration and a
      smaller laser fiber predict a popcorn technique that is more efficient at
      reducing stone volume.

PMID- 28442385
TI  - The Immediate Management of Pelvic Fracture Urethral Injury-Endoscopic
      Realignment or Cystostomy?
AB  - PURPOSE: We determined whether endoscopic realignment or cystostomy would provide
      the best immediate management of pelvic fracture urethral injury. MATERIALS AND
      METHODS: We retrospectively reviewed the records of 590 patients with pelvic
      fracture urethral injury. Of the patients 522 were included in analysis due to
      strict criteria, including 129 in the endoscopic realignment group and 393 in the
      cystostomy group. Data on stricture formation and length, intervention technique
      and long-term functional outcomes were analyzed. RESULTS: In the endoscopic
      realignment group stricture developed in 111 patients (83%) at a mean of 23.5
      months, which is longer than the 7.6 months reported in the cystostomy group (p
      <0.05). Mean stricture length was 3.2 cm in the realignment group and 3.7 cm in
      the cystostomy group (p <0.05). Internal urethrotomy was performed in 21 patients
      (19%) treated with realignment vs 18 (5%) treated with cystostomy (p <0.05).
      Further repair was accomplished via simple perineal anastomosis in 57 patients
      (51%) with realignment and 138 (35%) with cystostomy (p <0.05). Ancillary
      procedures such as corporeal splitting, inferior pubectomy and crural rerouting
      were necessary in 14 (13%), 14 (13%) and 5 patients (4%) in the endoscopic
      realignment group, and in 94 (24%), 100 (25%) and 43 (11%), respectively, in the
      cystostomy group (all p <0.05). The rates of impotence and incontinence did not
      statistically differ between the endoscopy and cystostomy groups (14.3% vs 16.2%
      and 1.6% vs 2.1%, respectively, p >0.05). CONCLUSIONS: Endoscopic realignment may
      reduce stricture formation and length, and facilitate urethroplasty. However,
      endoscopic realignment is also associated with a prolonged clinical course for
      recurrence.

PMID- 28442386
TI  - Arginine deiminase pathway provides ATP and boosts growth of the gas-fermenting
      acetogen Clostridium autoethanogenum.
AB  - Acetogens are attractive organisms for the production of chemicals and fuels from
      inexpensive and non-food feedstocks such as syngas (CO, CO2 and H2). Expanding
      their product spectrum beyond native compounds is dictated by energetics,
      particularly ATP availability. Acetogens have evolved sophisticated strategies to
      conserve energy from reduction potential differences between major redox couples,
      however, this coupling is sensitive to small changes in thermodynamic equilibria.
      To accelerate the development of strains for energy-intensive products from
      gases, we used a genome-scale metabolic model (GEM) to explore alternative ATP
      generating pathways in the gas-fermenting acetogen Clostridium autoethanogenum.
      Shadow price analysis revealed a preference of C. autoethanogenum for nine amino
      acids. This prediction was experimentally confirmed under heterotrophic
      conditions. Subsequent in silico simulations identified arginine (ARG) as a key
      enhancer for growth. Predictions were experimentally validated, and faster growth
      was measured in media containing ARG (tD~4h) compared to growth on yeast extract
      (tD~9h). The growth-boosting effect of ARG was confirmed during autotrophic
      growth. Metabolic modelling and experiments showed that acetate production is
      nearly abolished and fast growth is realised by a three-fold increase in ATP
      production through the arginine deiminase (ADI) pathway. The involvement of the
      ADI pathway was confirmed by metabolomics and RNA-sequencing which revealed a
      ~500-fold up-regulation of the ADI pathway with an unexpected down-regulation of
      the Wood-Ljungdahl pathway. The data presented here offer a potential route for
      supplying cells with ATP, while demonstrating the usefulness of metabolic
      modelling for the discovery of native pathways for stimulating growth or
      enhancing energy availability.

PMID- 28442387
TI  - Establishment of MicroRNA delivery system by PP7 bacteriophage-like particles
      carrying cell-penetrating peptide.
AB  - MicroRNAs have great therapeutic potential in cancer and other diseases. However,
      their instability and low in vivo delivery efficiency limits their application.
      Recombinant PP7 bacteriophage-based virus-like particles (VLPs) could protect
      microRNAs against rapid degradation by RNase by packaging specific exogenous pre
      microRNAs using the pac site. Insertion of a cell-penetrating peptide (CPP) into
      the AB-loop of VLPs could significantly improve the delivery efficiency of
      microRNAs into mammalian cells. Unlike other microRNA delivery methods (viral or
      non-viral vectors), recombinant PP7 VLPs carrying a CPP and microRNA could be
      efficiently expressed in Escherichia coli using the one-plasmid double expression
      system. Here we showed that PP7 VLPs carrying a CPP penetrated hepatoma SK-HEP-1
      cells and delivered the pre-microRNA-23b, which was processed into a mature
      product within 24 h; a concentration of 10 nM was sufficient for the inhibition
      of hepatoma cell migration via the downregulation of liver-intestine cadherin
      expression. Furthermore, PP7 VLPs carrying a CPP and a pre-microRNA were not
      infectious, replicative, or cytotoxic. Therefore, recombinant PP7 VLPs can be
      used for simultaneous and targeted delivery of both microRNAs and peptides
      because of their ability to package specific exogenous RNA using the pac site and
      to display peptides.

PMID- 28442388
TI  - Microbial secretion of lactate-enriched oligomers for efficient conversion into
      lactide: A biological shortcut to polylactide.
AB  - Recently, we have succeeded in establishing the microbial platform for the
      secretion of lactate (LA)-based oligomers (D-LAOs), which consist of D-LA and d-3
      hydroxybutyrate (d-3HB). The secretory production of D-LAOs was substantially
      enhanced by the supplementation of diethylene glycol (DEG), which resulted in the
      generation of DEG-capped oligomers at the carboxyl terminal (referred as D-LAOs
      DEG). The microbial D-LAOs should be key compounds for the synthesis of lactide,
      an important intermediate for polylactides (PLAs) production, eliminating the
      costly chemo-oligomerization step in the PLA production process. Therefore, in
      order to demonstrate a proof-of-concept, here, we attempted to convert the D-LAOs
      DEG into lactide via metal-catalyzed thermal depolymerization. As a result, D
      LAOs-DEG containing 68 mol% LA were successfully converted into lactide,
      revealing that the DEG bound to D-LAOs-DEG does not inhibit the conversion into
      lactide. However, the lactide yield (4%) was considerably lower than that of
      synthetic LA homo-oligomers (33%). We presumed that 3HB units in the polymer
      chain blocked the lactide formation, and therefore, we investigated the LA
      enrichment in the oligomers. As the results, the combination of an LA
      overproducing Escherichia coli mutant (Deltadld and DeltapflA) with the use of
      xylose as a carbon source exhibited synergistic effect to increase LA fraction in
      the oligomers up to 89 mol%. The LA-enriched D-LAOs-DEG were converted into
      lactide with greater yield (18%). These results demonstrated that a greener
      shortcut route for PLA production can be created by using the microbial D-LAOs
      secretion system.

PMID- 28442389
TI  - Gene identification and characterization of fucoidan deacetylase for potential
      application to fucoidan degradation and diversification.
AB  - Fucoidan is an alpha-l-fucopyranosyl polymer found in seaweeds with forms that
      have acetyl and sulfuric modifications and derivatives that are lower and/or
      diversified, with modifications that have attracted interest as potential
      bioactive substances. We identified the gene for a fucoidan deacetylase that
      cleaves acetyl moieties from fucoidan and thereby contributes to fucoidan
      utilization in the marine bacterium Luteolibacter algae H18. Fucoidan deacetylase
      was purified to homogeneity from a cell-free extract of L. algae H18, and used to
      determine the internal amino acid sequence and identify the gene, fud, in a draft
      genome sequence of the H18 strain. The gene product was heterologously produced
      in Escherichia coli and was demonstrated to catalyze fucoidan deacetylation, but
      not desulfation, and degradation into lower forms. In addition to fucoidan
      deacetylation, the enzyme catalyzed the hydrolysis of p-nitrophenyl esters with
      organic acids, and p-nitrophenyl acetate was the best substrate among those
      tested. The present study provides a new tool for fucoidan degradation,
      potentially expanding investigations on fucoidan derivatives.

PMID- 28442390
TI  - High-pressure thermophilic electromethanogenic system producing methane at 5 MPa,
      55 degrees C.
AB  - Toward applications of bio-electrochemical systems in industrial processes and
      extreme environments, electromethanogenesis under high-pressure conditions was
      examined. Stainless-steel single-chamber reactors specifically designed to
      examine bio-electrochemical reactions under pressurized conditions were
      inoculated with thermophilic microorganisms originated from an oilfield formation
      water. The reactors were incubated at 5 MPa, 55 degrees C in fed-batch
      operational mode with an applied voltage of 0.7 V. In the first few fed-batch
      cycles, hydrogen was mainly produced. After the third cycle, however, the
      reactors produced only methane simultaneously with current generation. The
      methane-production rate of the reactors showed an applied-voltage dependence and
      increased from 34.9 to 168.4 mmol m-2 day-1 with an increase in the applied
      voltage from 0.4 to 0.9 V. The efficiency of capturing electrons in the produced
      methane on average exceeded 70% with the applied voltage of 0.4 V or higher.
      Cyclic voltammetry further confirmed abilities of the bioelectrodes to catalyze
      electrochemical reactions at 5 MPa. Performance of the electromethanogenesis
      system was not altered under lower pressure conditions (1.2 and 2.5 MPa). An
      exoelectrogenic bacterium affiliated with the genus Thermincola and a methanogen
      belonging to the genus Methanothermobacter were detected as the dominant species
      in the bioanode and biocathode microbiotas, respectively. Thus, our results
      indicated that electromethanogenesis systems could be developed and operated
      under highly-pressurized conditions, suggesting that applications of the bio
      electrochemical system in high-pressure environments (including high-temperature
      subsurface reservoirs) can be technically feasible.

PMID- 28442391
TI  - An exploratory high-density EEG investigation of the misinformation effect:
      Attentional and recollective differences between true and false perceptual
      memories.
AB  - The misinformation effect, a phenomenon in which eyewitness memories are altered
      via exposure to post-event misinformation, is one of the most important paradigms
      used to investigate the reconstructive nature of human memory. The aim of this
      study was to use the misinformation effect paradigm to investigate differences in
      attentional and recollective processing between true and false event memories.
      Nineteen participants completed a variant of the misinformation paradigm in which
      recognition responses to true and misinformation based event details embedded
      within a narrative context, were investigated using high-density (256-channel)
      EEG with a 1-day delay between event exposure and test. Source monitoring
      responses were used to isolate event-related-potentials (ERPs) associated with
      perceptual (i.e. event) source attributions. Temporal-spatial analyses of these
      ERPs showed evidence of an elevated P3b and Late-Positive Component, associated
      with stronger context-matching responses and recollective activity respectively,
      in true perceptual memories relative to false misinformation based ones. These
      findings represent the first retrieval focused EEG investigation of the
      misinformation effect and highlight the interplay between attention and retrieval
      processes in episodic memory recognition.

PMID- 28442392
TI  - 4'-Chlorodiazepam is neuroprotective against amyloid-beta in organotypic
      hippocampal cultures.
AB  - The translocator protein (TSPO) is an outer mitochondrial membrane protein
      involved in the transport of cholesterol into the mitochondria, which is the
      first step for the synthesis of steroid hormones, as well as in the regulation of
      mitochondrial permeability transition pore opening and apoptosis. Studies have
      shown that the activation of TSPO may promote neuroprotective actions in
      experimental models of neurodegeneration and brain injury. In a previous study,
      our group showed that 4'-chlorodiazepam (4'-CD), a TSPO ligand, was
      neuroprotective against amyloid-beta (Abeta) in SHSY-5Y neuroblastoma cells. The
      aim of this study was to evaluate if 4'-CD was also neuroprotective against Abeta
      in organotypic hippocampal cultures and to identify its mechanisms of action.
      Abeta decreased the cell viability of organotypic hippocampal cultures, while 4'
      CD had a neuroprotective effect when administered at 100nM and 1000nM. The
      neuroprotective effects of 4'-CD against Abeta were associated with an increased
      expression of superoxide dismutase (SOD). No differences were found in the
      expression of catalase, glial fibrillary acidic protein, Akt and procaspase-3. In
      summary, our results show that 4'-CD is neuroprotective against Abeta by a
      mechanism involving the modulation of SOD protein expression.

PMID- 28442394
TI  - Granin-derived peptides.
AB  - The granin family comprises altogether 7 different proteins originating from the
      diffuse neuroendocrine system and elements of the central and peripheral nervous
      systems. The family is dominated by three uniquely acidic members, namely
      chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). Since the
      late 1980s it has become evident that these proteins are proteolytically
      processed, intragranularly and/or extracellularly into a range of biologically
      active peptides; a number of them with regulatory properties of physiological
      and/or pathophysiological significance. The aim of this comprehensive overview is
      to provide an up-to-date insight into the distribution and properties of the well
      established granin-derived peptides and their putative roles in homeostatic
      regulations. Hence, focus is directed to peptides derived from the three main
      granins, e.g. to the chromogranin A derived vasostatins, betagranins,
      pancreastatin and catestatins, the chromogranin B-derived secretolytin and the
      secretogranin II-derived secretoneurin (SN). In addition, the distribution and
      properties of the chromogranin A-derived peptides prochromacin, chromofungin,
      WE14, parastatin, GE-25 and serpinins, the CgB-peptide PE-11 and the SgII
      peptides EM66 and manserin will also be commented on. Finally, the opposing
      effects of the CgA-derived vasostatin-I and catestatin and the SgII-derived
      peptide SN on the integrity of the vasculature, myocardial contractility,
      angiogenesis in wound healing, inflammatory conditions and tumors will be
      discussed.

PMID- 28442395
TI  - Association of genetic variations in IL-6/IL-6R pathway genes with gastric cancer
      risk in a Chinese population.
AB  - Interleukin-6 (IL-6) and its receptor (IL-6R) were regarded to be responsible for
      the occurrence of gastric cancer for their regulation roles in the inflammation.
      The genetic variations in these two genes (IL-6: rs6949149, rs1800796, rs10499563
      and IL-6R: rs2228145) have been suggested to be associated with gastric cancer
      risk. However, the published results were inconsistent among subjects of
      different ethnicity. To evaluate such an association in Chinese population, we
      carried out this case-control study based on 473 patients with gastric cancer and
      474 healthy controls, whose genotypes were detected by the Sequenom MassARRAY
      platform, and Helicobacter pylori infection was assessed by immunogold testing
      kit. This study showed that rs1800796 CG genotype was associated with decreased
      risk of gastric cancer (adjusted OR=0.75, 95% CI: 0.57-0.99, p=0.043). The
      stratified analysis revealed that, in the Helicobacter pylori negative infection
      subgroup, rs2228145 AC (adjusted OR=0.64, 95% CI: 0.42-0.97) and AC/CC (adjusted
      OR=0.66, 95% CI: 0.45-0.99) genotypes were associated with decreased risk of
      gastric cancer, respectively. In contrast, in the Helicobacter pylori positive
      infection subgroup, rs10499563 TC (adjusted OR=0.64, 95% CI: 0.43-0.95), CC
      (adjusted OR=0.35, 95% CI: 0.14-0.90), TC/CC (adjusted OR=0.59, 95% CI: 0.40
      0.87) genotype were associated with decreased gastric cancer risk, respectively.
      Moreover, in the male subgroup, rs1800796 CG (adjusted OR=0.61, 95% CI: 0.44
      0.84) and CG/GG (adjusted OR=0.67, 95% CI: 0.49-0.91) genotype were associated
      with decreased risk of gastric cancer, respectively. In short, this study
      suggested that IL-6R rs2228145 and IL-6 rs10499563 genotype were associated with
      decreased risk of gastric cancer for the individuals with negative and positive
      Helicobacter pylori infection.

PMID- 28442393
TI  - Progesterone receptors (PR) mediate STAT actions: PR and prolactin receptor
      signaling crosstalk in breast cancer models.
AB  - Estrogen is the major mitogenic stimulus of mammary gland development during
      puberty wherein ER signaling acts to induce abundant PR expression. PR signaling,
      in contrast, is the primary driver of mammary epithelial cell proliferation in
      adulthood. The high circulating levels of progesterone during pregnancy signal
      through PR, inducing expression of the prolactin receptor (PRLR). Cooperation
      between PR and prolactin (PRL) signaling, via regulation of downstream components
      in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar
      morphogenesis observed during pregnancy. Indeed, these pathways are fully
      integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well
      as by the convergence of PRs and STATs at target genes relevant to both mammary
      gland biology and breast cancer progression (i.e. proliferation, stem cell
      outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator
      such as ER, transcription factor cascades (ER>PR>STATs) are responsible for rapid
      proliferative and developmental programming in the normal mammary gland. It is
      not surprising that these same mediators typify uncontrolled proliferation in a
      majority of breast cancers, where ER and PR are most often co-expressed and may
      cooperate to drive malignant tumor progression. This review will primarily focus
      on the integration of PR and PRL signaling in breast cancer models and the
      importance of this cross-talk in cancer progression in the context of
      mammographic density. Components of these PR/PRL signaling pathways could offer
      alternative drug targets and logical complements to anti-ER or anti-estrogen
      based endocrine therapies.

PMID- 28442396
TI  - Fas and Fas ligand gene polymorphisms in Turkish patients with Familial
      Mediterranean Fever.
AB  - Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory
      disorder characterized by recurrent fever, serositis, abdominal pain, arthritis,
      arthralgia and erysipelas like erythema. Fas and Fas ligand molecules play a
      central role in the apoptosis signaling of various cell types including
      neutrophils. Neutrophils are the major cell population involved in acute
      inflammation in patients with FMF and the role of Fas and Fas ligand molecules in
      this cells of FMF patients may be crucial. Therefore, in the present study, we
      aimed to investigate whether the Fas cell surface receptor gene (FAS);
      NM_000043.5: c.-671A>G (rs1800682, MvaI) and Fas ligand gene (FASLG),
      NM_000639.2: c.-844C>T (rs763110, BsrD1) functional polymorphisms in patients
      with FMF and their relation to the main clinical features of the disease. The
      polymorphisms in the promoter regions of FAS c.-671A>G and FASLG c.-844C>T were
      investigated in 97 non-related FMF patients and 70 non-related healthy controls
      by using PCR-RFLP technique. The frequencies of FAS c-671AG genotype and G allele
      were not significantly different between FMF patients and healthy subjects. The
      frequency of FASLG -844TC genotype was found significantly different between the
      patients with FMF and healthy controls whereas T or C allele frequency was not
      significantly different between the groups. Haplotype frequencies of the studied
      polymorphisms were also not significantly different between FMF patients and
      controls. There were no correlations between the studied FAS c.-671A>G and FASLG
      c.-844C>T polymorphisms and the main clinical features of FMF such as fever,
      arthritis, abdominal and chest pain, arthralgia and erysipelas-like erythema. Our
      findings suggest that FAS c.-671AG genotype or G allele and FASLG c.-844 allele
      are not to be a risk factor, whereas FASLG c.-844TC genotype may be protective in
      the studied Turkish population. According to our results we may suggest that
      although not statistically significant, higher frequencies of FASLG c.-844CC
      genotype in FMF patients may be related to delayed apoptosis of neutrophils and
      ultimately cause neutrophilic inflammation by increasing FASLG expression.

PMID- 28442397
TI  - Molecular cloning, characterization and expression analysis of heat shock protein
      90 in albino northern snakehead Channa argus.
AB  - The great albino northern snakehead Channa argus is habitual to only the Sichuan
      Jialing Rivers System in China, making its introduction difficult to other
      riverine systems. Here, we characterized heat shock protein 90 (AcaHSP90) and
      probed its molecular responses toward the environmental stressors that C. argus
      can face during its introduction and breeding in the other southern latitudes of
      China. To serve the purpose, cDNA encoding of AcaHSP90 were cloned and
      characterized in albino C. argus. The cDNA was 2752bps that contained an open
      reading frame (ORF), encoding a 726-amino-acid polypeptide of 83.35kDa
      (theoretical isoelectric point [pI]: 4.89). Genomic DNA analysis showed that the
      AcaHSP90 gene consisted of 7 introns, five conserved amino acid blocks and other
      motifs or domains. The AcaHSP90 structure was highly similar with the other known
      HSP90s except those identified in the bacteria. The expression profiles of
      AcaHSP90 gene in albino C. argus were also investigated after experimentally
      exposed to different temperature stresses (8.5, 26 and 37 degrees C) and infected
      with Edwardsiella tarda (strain NO. DL1476) at different time intervals (0, 6,
      12, 24, 36, 48, 72h). In addition, the AcaHSP90 expression in different tissues
      of albino C. argus were also analyzed. The quantitative real-time PCR and western
      blot analysis revealed tissue-specific AcaHSP90 expressions in control group, and
      expressions were significantly stimulated in the brain, heart, kidney, liver,
      muscle and spleen after the heat shock (37 degrees C), while showed no
      significant difference after the cold treatment (8.5 degrees C). The mRNA levels
      of AcaHSP90 were also significantly upregulated in the spleen and muscle at 12h
      and in the kidney at 12 and 48h post pathogen injections. In a nut shell, these
      novel results showed tissue-specific responses of AcaHSP90 and indicated that
      this heat shock protein might also be sensitive to pathogen infection, but
      closely related to the thermal resistance in albino C. argus.

PMID- 28442398
TI  - Association of a novel genetic variant in RP11-650L12.2 with risk of colorectal
      cancer in Han Chinese population.
AB  - BACKGROUND: This study aimed to investigate the associations of selected
      polymorphisms in RP11-650L12.2 with the risk of colorectal cancer (CRC) in a
      Chinese population. METHODS: A total of 821 CRC cases (test set: 320, validation
      set: 501) and 857 healthy controls (test set: 319, validation set: 538) were
      enrolled in this study. Demographic characteristics and lifestyle information
      were collected by a validated questionnaire. A sample of 5ml venous blood was
      collected from each subject for DNA isolation, and the selected polymorphisms
      (rs144182521, rs514743, rs76071148, rs149941240) were genotyped by MassArray
      technique. RESULTS: The rs149941240 polymorphism was significantly associated
      with the risk of CRC, with ORs of 1.50 (95% CI: 1.15-1.96) by co-dominant model
      and 1.45 (95% CI: 1.21-1.87) by dominant model in the test set, respectively.
      Correspondingly, the ORs were 1.48 (95% CI: 1.19-1.82) and 1.41 (95% CI: 1.15
      1.73) in the validation set, respectively. The crossover analysis showed that non
      smokers with the variant genotypes in rs149941240 had a significantly increased
      risk of CRC than those with wild genotype by dominant model in the validation set
      (OR 1.42, 95% CI 1.04-1.96). However, no gene-environment multiplicative
      interactions of rs149941240 with tobacco smoking were found on risk of CRC.
      CONCLUSIONS: Our findings suggest that rs149941240 polymorphism was associated
      with the risk of CRC, and might contribute to the susceptibility to CRC. The
      effects of this polymorphism should be validated in a larger sample and require
      further mechanistic investigations to determine the nature of its influence on
      CRC.

PMID- 28442399
TI  - The genome sequence of Agrotis segetum granulovirus, isolate AgseGV-DA, reveals a
      new Betabaculovirus species of a slow killing granulovirus.
AB  - The European isolate Agrotis segetum granulovirus DA (AgseGV-DA) is a slow
      killing, type I granulovirus due to low dose-mortality responses within seven
      days post infection and a tissue tropism of infection restricted solely to the
      fat body of infected Agrotis segetum host larvae. The genome of AgseGV-DA was
      completely sequenced and compared to the whole genome sequences of the Chinese
      isolates AgseGV-XJ and AgseGV-L1. All three isolates share highly conserved
      genomes. The AgseGV-DA genome is 131,557bp in length and encodes for 149 putative
      open reading frames, including 37 baculovirus core genes and the per os
      infectivity factor ac110. Comprehensive investigations of repeat regions
      identified one putative non-hr like origin of replication in AgseGV-DA.
      Phylogenetic analysis based on concatenated amino acid alignments of 37
      baculovirus core genes as well as pairwise distances based on the nucleotide
      alignments of partial granulin, lef-8 and lef-9 sequences with deposited
      betabaculoviruses confirmed AgseGV-DA, AgseGV-XJ and AgseGV-L1 as representative
      isolates of the same Betabaculovirus species. AgseGV encodes for a distinct
      putative enhancin, distantly related to enhancins from other granuloviruses.

PMID- 28442400
TI  - Laboratory evaluation of Brevibacillus laterosporus strains as biocidal agents
      against Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae) larvae.
AB  - The biocidal activity of three strains of Brevibacillus laterosporus upon the
      post-embryonic developmental stages of Chrysomya megacephala was evaluated.
      Bioassays were performed to verify lethal and sub-lethal effects including ultra
      structural changes in the midgut. Among the strains assayed, Shi3 presented the
      highest larval mortality rates, achieving 70% at a concentration of 1*108
      spores/g of diet. Transmission electron microscopy revealed intestinal
      alterations caused by all strains tested. The findings of this study indicate
      that Shi3 represents a promising tool for use in the biocontrol of C.
      megacephala.

PMID- 28442401
TI  - TRIB3 downregulation enhances doxorubicin-induced cytotoxicity in gastric cancer
      cells.
AB  - TRIB3, which is a pseudokinase known to regulate multiple pro-survival pathways,
      appears to be a potential therapeutic target for the treatment of human tumors.
      However, its precise role in cancer is controversial, as TRIB3 protein levels
      have been associated with both good and poor prognosis in cancer patients. Here,
      we investigated the significance of TRIB3 expression in the survival of gastric
      cancer cells exposed to anticancer drugs. We found that the tested anticancer
      drug, doxorubicin, induced cytotoxicity by decreasing TRIB3 transcription, which
      was followed by apoptotic cell death. Moreover, TRIB3 siRNA knockdown appeared to
      enhance doxorubicin-induced apoptosis in gastric cancer cells, concurrently with
      altering the expression of downstream apoptotic factors. Conversely,
      overexpression of TRIB3 significantly protected cells against doxorubicin-induced
      apoptosis. Our results indicate that downregulation of TRIB3 appears to promote
      cell death and enhance doxorubicin-induced apoptosis, supporting the anti
      apoptotic role of TRIB3. The inductions of three classes of MAPKs failed to
      affect doxorubicin-mediated TRIB3 downregulation, while TRIB3 overexpression did
      not affect doxorubicin-induced MAPK activation. In sum, our findings indicate
      that TRIB3 plays an anti-apoptotic role in doxorubicin-treated gastric cancer
      cell lines, perhaps indicating that the status of TRIB3 expression in response to
      anticancer drugs, such as doxorubicin, irinotecan or oxaliplatin, may reflect the
      efficiency for cancer therapy.

PMID- 28442403
TI  - The correlation between central and peripheral oxytocin concentrations: A
      systematic review and meta-analysis.
AB  - There is growing interest in the role of the oxytocin system in social cognition
      and behavior. Peripheral oxytocin concentrations are regularly used to
      approximate central concentrations in psychiatric research, however, the validity
      of this approach is unclear. Here we conducted a pre-registered systematic search
      and meta-analysis of correlations between central and peripheral oxytocin
      concentrations. A search of databases yielded 17 eligible studies, resulting in a
      total sample size of 516 participants and subjects. Overall, a positive
      association between central and peripheral oxytocin concentrations was revealed
      [r=0.29, 95% CI (0.14, 0.42), p<0.0001]. This association was moderated by
      experimental context [Qb(4), p=0.003]. While no association was observed under
      basal conditions (r=0.08, p=0.31), significant associations were observed after
      intranasal oxytocin administration (r=0.66, p<0.0001), and after experimentally
      induced stress (r=0.49, p=0.001). These results indicate a coordination of
      central and peripheral oxytocin release after stress and after intranasal
      administration. Although popular, the approach of using peripheral oxytocin
      levels to approximate central levels under basal conditions is not supported by
      the present results.

PMID- 28442404
TI  - Meta-analytic investigations of common and distinct grey matter alterations in
      youths and adults with obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a disabling illness with onset generally
      in childhood. OCD-youths differ from OCD-adults with regard to gender
      distribution, comorbidity patterns and treatment options. However, little is
      known about the neural correlate differences underpin those two populations. The
      current meta-analysis summarizes voxel based morphometry findings to elucidate
      whether differences of neural correlates exist between these two populations.
      Both OCD-youths and OCD-adults demonstrated greater striatal volume and smaller
      prefrontal grey matter volume (GMV). However, smaller GMV in left visual cortex
      was observed in OCD-youths only, while smaller GMV in anterior cingulate gyrus
      and greater GMV in cerebellum were demonstrated only in OCD-adults. Meta
      regression showed greater GMV in left putamen was most prominent in samples with
      higher percentages of medicated OCD-adults. Our findings confirmed the most
      consistent GMV alterations in OCD were in prefrontal-striatal circuitry. Besides,
      other regions may involve at different developmental stages including deficits of
      visual cortex in OCD-youths and abnormalities of limbic-cerebellar circuit in OCD
      adults. Medication effect may be more pronounced in the striatum, especially the
      putamen.

PMID- 28442402
TI  - Chromatic clocks: Color opponency in non-image-forming visual function.
AB  - During dusk and dawn, the ambient illumination undergoes drastic changes in
      irradiance (or intensity) and spectrum (or color). While the former is a well
      studied factor in synchronizing behavior and physiology to the earth's 24-h
      rotation, color sensitivity in the regulation of circadian rhythms has not been
      systematically studied. Drawing on the concept of color opponency, a well-known
      property of image-forming vision in many vertebrates (including humans), we
      consider how the spectral shifts during twilight are encoded by a color-opponent
      sensory system for non-image-forming (NIF) visual functions, including phase
      shifting and melatonin suppression. We review electrophysiological evidence for
      color sensitivity in the pineal/parietal organs of fish, amphibians and reptiles,
      color coding in neurons in the circadian pacemaker in mice as well as sporadic
      evidence for color sensitivity in NIF visual functions in birds and mammals.
      Together, these studies suggest that color opponency may be an important
      modulator of light-driven physiological and behavioral responses.

PMID- 28442405
TI  - The effect of active video games on cognitive functioning in clinical and non
      clinical populations: A meta-analysis of randomized controlled trials.
AB  - Physically-active video games ('exergames') have recently gained popularity for
      leisure and entertainment purposes. Using exergames to combine physical activity
      and cognitively-demanding tasks may offer a novel strategy to improve cognitive
      functioning. Therefore, this systematic review and meta-analysis was performed to
      establish effects of exergames on overall cognition and specific cognitive
      domains in clinical and non-clinical populations. We identified 17 eligible RCTs
      with cognitive outcome data for 926 participants. Random-effects meta-analyses
      found exergames significantly improved global cognition (g=0.436, 95% CI=0.18
      0.69, p=0.001). Significant effects still existed when excluding waitlist-only
      controlled studies, and when comparing to physical activity interventions.
      Furthermore, benefits of exergames where observed for both healthy older adults
      and clinical populations with conditions associated with neurocognitive
      impairments (all p<0.05). Domain-specific analyses found exergames improved
      executive functions, attentional processing and visuospatial skills. The findings
      present the first meta-analytic evidence for effects of exergames on cognition.
      Future research must establish which patient/treatment factors influence efficacy
      of exergames, and explore neurobiological mechanisms of action.

PMID- 28442407
TI  - Light/magnetic hyperthermia triggered drug released from multi-functional thermo
      sensitive magnetoliposomes for precise cancer synergetic theranostics.
AB  - Precise delivery of antineoplastic drugs to specific tumor region has drawn much
      attention in recent years. Herein, a light/magnetic hyperthermia triggered drug
      delivery with multiple functionality is designed based on methotrexate (MTX)
      modified thermo-sensitive magnetoliposomes (MTX-MagTSLs). In this system, MTX and
      oleic acid modified magnetic nanoparticles (MNPs) can be applied in biological
      and magnetic targeting. Meanwhile, lipophilic fluorescent dye Cy5.5 and MNPs are
      encapsulated into the bilayer of liposomes, which can not only achieve dual
      imaging effect to verify the MTX-MagTSLs accumulation in tumor region, but also
      provide an appropriate laser irradiation region to release Doxorubicin (Dox)
      under alternating magnetic field (AMF). Both in vitro and in vivo results
      revealed that MTX-MagTSLs possessed an excellent targeting ability towards HeLa
      cells and HeLa tumor-bearing mice. Furthermore, the heating effect of MTX-MagTSLs
      was amplified 4.2-fold upon combination with AMF and local precise near-infrared
      laser irradiation (808nm) (DUAL-mode) to rapidly reach the phase change
      temperature (Tm) of MTX-MagTSLs in 5min compared with either AMF or laser
      stimulation alone, resulting in a significantly enhanced release of Dox at tumor
      region and precise cancer synergetic theranostics.

PMID- 28442406
TI  - Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum
      harmala on scopolamine-induced memory deficits in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is
      used as traditional medical herb for treatment of forgetfulness in Uighur
      medicine in China. But, the active ingredients and underlying mechanisms are
      unclear. AIM OF THE STUDY: The present study was undertaken to investigate the
      improvement effects of extract and alkaloid fraction from APP on scopolamine
      induced cognitive dysfunction and to elucidate their underlying mechanisms of
      action, and to support its folk use with scientific evidence, and lay a
      foundation for its further researches. MATERIALS AND METHODS: The
      acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid
      fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal
      male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured
      in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks.
      The levels of biomarkers, enzyme activity and protein expression of cholinergic
      system were determined in brain tissues. RESULTS: The AChE activity was
      significantly decreased and the content of neurotransmitter acetylcholine (ACh)
      was significantly increased in normal mice cortex and hippocampus by treatment
      with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650mg/kg and ALK
      at dosages of 10, 30, 90mg/kg (P<0.05), and the AChE activity and the content of
      ACh were not significantly changed in cortex and hippocampus after treatment with
      FLA at dosages of 10, 30, 90mg/kg (P>0.05). In the MWM task, scopolamine-induced
      a decrease in both the swimming time within the target zone and the number of
      crossings where the platform had been placed were significantly reversed by
      treatment with EXT at dosages of 550, 1650mg/kg and ALK at dosages of 30, 90mg/kg
      (P<0.05). Moreover, the activity and protein expression of AChE was significantly
      decreased and the content of neurotransmitter ACh was significantly increased in
      cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of
      183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), compared with
      scopolamine-treated group. CONCLUSIONS: EXT and ALK from APP exert beneficial
      effect on learning and memory processes in mice with scopolamine-induced memory
      impairment. APP is an effective traditional folk medicine and the ALK fraction is
      proved to be the main effective components for the treatment of forgetfulness.
      The ALK may be valuable source for lead compounds discovery and drug development
      for treatment of memory impairment such as in Alzheimer's disease.

PMID- 28442408
TI  - Plasma membrane activatable polymeric nanotheranostics with self-enhanced light
      triggered photosensitizer cellular influx for photodynamic cancer therapy.
AB  - To address the issue of low cellular uptake of photosensitizers by cancer cells
      in photodynamic therapy (PDT), we designed a smart plasma membrane-activatable
      polymeric nanodrug by conjugating the photosensitizer protoporphyrin IX (PpIX)
      and polyethylene glycol (PEG) with glycol chitosan (GC). The as-prepared GC-PEG
      PpIX can self-assemble into core-shell nanoparticles (NPs) in aqueous solution
      and the fluorescence of PpIX moieties in the inner core is highly quenched due to
      strong pi-pi stacking. Interestingly, when encountering plasma membranes, the GC
      PEG-PpIX NPs can disassemble and stably attach to plasma membranes due to the
      membrane affinity of PpIX moieties, which effectively suppresses the self
      quenching of PpIX, leading to significantly enhanced fluorescence and singlet
      oxygen (1O2) production upon laser irradiation. The massively produced 1O2 can
      compromise the integrity of the plasma membrane, enabling the influx of
      extracellular nanoagents into cells to promote cell death upon further laser
      irradiation. Through local injection, the membrane anchored GC-PEG-PpIX enables
      strong physical association with tumor cells and exhibits highly enhanced in vivo
      fluorescence at the tumor site. Besides, excellent tumor accumulation and
      prolonged tumor retention of GC-PEG-PpIX were realized after intravenous
      injection, which ensured its effective imaging-guided PDT.

PMID- 28442409
TI  - Sinonasal mucosal melanoma: A 44-case study and literature analysis.
AB  - OBJECTIVES: Sinonasal mucosal melanoma is a rare disease, representing 4% of
      nasal cavity and paranasal sinus malignancies. The aim of this study was to
      assess the clinical characteristics, progression and treatment of this disease
      and to identify prognostic factors. MATERIAL AND METHODS: This retrospective
      review presents a cohort of 44 patients treated for a melanoma arising from the
      nasal cavity and paranasal sinuses, in the ENT Head and Neck Surgery Department
      of the University Hospital of Nantes (France) between 1988 and 2015. RESULTS:
      Mean age at diagnosis was 71.2 years. The main signs at diagnosis were epistaxis
      and unilateral nasal obstruction. 25% of patients were initially classified as
      T4. Surgical treatment was performed in 42 patients. Postoperative radiotherapy
      was performed in 19 cases and adjuvant immunotherapy in 14 cases. Mean follow-up
      was 50 months. Cumulative overall survival was 71.5% at 1 year and 33% at 5
      years. Clinically, headache, facial pain and trigeminal V2 nerve anesthesia were
      significant factors for poor prognosis. Exclusively nasal involvement was a
      factor for better overall survival than sinus involvement. Adjuvant radiation
      therapy showed a non-significant trend toward improved local control.
      CONCLUSIONS: Mucosal melanoma of the sinonasal cavities has poor prognosis due to
      high metastatic potential. Surgical resection followed by radiation therapy is
      the main treatment. There is no consensus regarding new systemic adjuvant
      treatments in this indication, unlike for primary cutaneous melanoma.

PMID- 28442410
TI  - Subchronic feeding study of high-free-lysine transgenic rice in Sprague-Dawley
      rats.
AB  - Lysine is considered to be the first essential amino acid in rice. An elite High
      Free-Lysine transgenic line HFL1 was previously produced by metabolic engineering
      to regulate lysine metabolism. In this study, a 90-day toxicology experiment was
      undertaken to investigate the potential health effect of feeding different doses
      of HFL1 rice to Sprague-Dawley rats. During the trial, body weight gain, food
      consumption and food efficiency were recorded, and no adverse effect was observed
      in rats fed transgenic (T) rice diets compared with non-transgenic (N) or control
      diets. At both midterm and final assessments, hematological parameters and serum
      chemistry were measured, and organ weights and histopathology were examined at
      the end of the trial. There was no diet-related difference in most hematological
      or serum chemistry parameters or organ weights between rats fed the T diets and
      those fed the N or control diets. Some parameters were found to differ between T
      groups and their corresponding N and/or control groups, but no adverse
      histological effect was observed. Taken together, the data from the current trial
      demonstrates that high lysine transgenic rice led to no adverse effect in Sprague
      Dawley rats given a diet containing up to 70% HFL1 rice in 90 days.

PMID- 28442411
TI  - Evaluation of the bioactive extract of actinomyces isolated from the Egyptian
      environment against aflatoxin B1-induce cytotoxicity, genotoxicity and oxidative
      stress in the liver of rats.
AB  - This study aimed to determine the bioactive compounds of actinomyces (ACT)
      isolated from the Egyptian environment (D-EGY) and to evaluate their protective
      activity against AFB1 in female Sprague-Dawley rats. Six groups of animals were
      treated orally for 3 weeks included: C, the control group, T1, AFB1-treated group
      (80 MUg/kg b.w), T2 and T3, the groups received ACT extract at low (25 mg/kg b.w)
      or high (50 mg/kg b.w) doses, T4 and T5, the groups received AFB1 plus the low or
      high dose of ACT extract. Blood, bone marrow and tissue samples were collected
      for different analyses and histological examination. The results revealed the
      identification of 40 components, representing 99.98%. Treatment with AFB1
      disturbs liver function parameters, oxidative stress markers, antioxidant gene
      expressions, DNA fragmentation and induced severe histological changes. ACT
      extract at the low or high doses did not induce significant changes in all the
      tested parameters or histological picture of the liver. Moreover, ACT extract
      succeeded to induce a significant protection against the toxicity of AFB1. It
      could be concluded that the bioactive compounds in ACT are promise candidate for
      the development of food additive or drugs for the protection and treatment of
      liver disorders in the endemic area.

PMID- 28442412
TI  - HSCCC separation and enantiomeric distribution of key volatile constituents of
      Piper claussenianum (Miq.) C. DC. (Piperaceae).
AB  - High Speed Countercurrent Chromatography (HSCCC) technique was used for the
      preparative isolation of the major leishmanicidal compounds from the essential
      oils of Piper claussenianum species in Brazil. The essential oils from
      inflorescences of P. claussenianum were analyzed by GC-FID and GC-MS. The
      enantiomeric ratio of the major constituents of the P. claussenianum essential
      oils were determined using a Rt-DEXsm chiral capillary column by GC-FID analysis.
      It was found an enantiomeric excess of (+)-(E)-nerolidol in the leaves, and (+)
      linalool and (+)-(E)-nerolidol in the inflorescences essential oil. The major
      volatile terpenes alcohols were isolated in preparative scale from
      inflorescences: linalool (320.0 mg) and nerolidol (95.0 mg) in high purity level.
      The HSCCC, a support-free liquid-liquid partition chromatographic technique,
      proved to be an effective and useful method for fast isolation and purification
      of hydrophobic and similarly structured bioactive components from essential oils
      of Piper species.

PMID- 28442413
TI  - Cytoprotective action against oxidative stress in astrocytes and neurons by
      Bactris guineensis (L.) H.E. Moore (corozo) fruit extracts.
AB  - Neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease and
      amyotrophic lateral sclerosis are characterized by having a significant increase
      in oxidative stress that can lead to the cellular damage of both neurons and
      astrocytes. Therefore, the search for molecules that can modulate oxidative
      stress in these diseases has recently gain interest, especially for those non
      traditional antioxidants that can be gained from diet. In the present work, pulp
      and seed extracts from the fruit of the palm, Bactris guineensis were obtained by
      hydro-alcoholic solution and by a solid-liquid phase using solvents with
      different polarities and evaluated for their capacity to protect both neurons and
      astrocytes against rotenone-induced oxidative stress. Analysis of the chemical
      antioxidant activity showed that Bactris guineensis pulp crude extract and seed
      ethyl acetate and ethanol extracts had a high scavenging capacity when compared
      with extracts obtained in Hexane and dichloromethane. Toxicity assays also showed
      that the pulp crude extract and seed ethyl acetate and ethanol extracts at low
      doses did not affect the cell viability of primary astrocyte and SH-SY5Y
      neuroblastoma cells. In addition, ethyl acetate and ethanol extracts, not only
      decreased O2- radicals production but also protected both SHSY5Y and astrocytes
      oxidative stress induced by rotenone. Together our results suggest that Bactris
      guineensis fruit contain antioxidant molecules that can have therapeutic
      potential.

PMID- 28442414
TI  - Inhibition of allogeneic cytotoxic T cell (CD8+) proliferation via polymer
      induced Treg (CD4+) cells.
AB  - : T cell-mediated immune rejection remains a barrier to successful
      transplantation. Polymer-based bioengineering of cells may provide an effective
      means of preventing allorecognition and the proliferation of cytotoxic (CD8+) T
      lymphocytes (CTL). Using MHC-disparate murine splenocytes modified with
      succinimidyl valerate activated methoxypoly(ethylene glycol) [SVA-mPEG] polymers,
      the effects of leukocyte immunocamouflage on CD8+ and CD4+ alloproliferation and
      T regulatory (Treg) cell induction were assessed in a mixed lymphocyte reaction
      (MLR) model. Polymer-grafting effectively camouflaged multiple leukocyte markers
      (MHC class I and II, TCR and CD3) essential for effective allorecognition.
      Consequent to the polymer-induced immunocamouflage of the cell membrane, both
      CD8+ and CD4+ T cell alloproliferation were significantly inhibited in a polymer
      dose-dependent manner. The loss of alloproliferation correlated with the
      induction of Treg cells (CD4+CD25+Foxp3+). The Tregs, surprisingly, arose
      primarily via differentiation of naive, non-proliferating, CD4+ cells. Of
      biologic importance, the polymer-induced Treg were functional and exhibited
      potent immunosuppressive activity on allogeneic CTL proliferation. These results
      suggest that immunocamouflage-mediated attenuation of alloantigen-TCR recognition
      can prevent the tissue destructive allogeneic CD8+ T cell response, both directly
      and indirectly, through the generation/differentiation of functional Tregs.
      Immunocamouflage induced tolerance could be clinically valuable in attenuating T
      cell-mediated transplant rejection and in the treatment of autoimmune diseases.
      STATEMENT OF SIGNIFICANCE: While our previous studies have demonstrated that
      polymer-grafting to MHC disparate leukocytes inhibits CD4+ cell proliferation,
      the effects of PEGylation on the alloproliferation of CD8+ cytotoxic T cells
      (CTL) was not examined. As shown here, PEGylation of allogeneic leukocytes
      prevents the generation of the CTL response responsible for acute rejection. The
      loss of CTL proliferation is consequent to the polymer-based attenuation of
      allorecognition and the induction of T regulatory cells (Tregs). Interestingly,
      the Tregs are primarily generated via the differentiation of non-proliferating
      naive T cells. Importantly, the Tregs are functional and effectively induce a
      tolerogenic environment when transferred to an alloresponsive environment. The
      use of polymer-modified leukocytes provides a unique approach to effectively
      maximize the biologic production of functional Tregs both in vitro and in vivo.
      By using this approach it may be possible to attenuate unwanted alloresponses
      (e.g., graft rejection) or to treat autoimmune diseases.

PMID- 28442415
TI  - Retro-inverso d-peptide-modified hyaluronic acid/bioreducible hyperbranched
      poly(amido amine)/pDNA core-shell ternary nanoparticles for the dual-targeted
      delivery of short hairpin RNA-encoding plasmids.
AB  - : The active targeting of gene carriers is a powerful strategy for improving
      tumour-specific delivery and therapy. Although numerous l-peptide ligands play
      significant roles in the active targeting of nanomedicine, retro-inverso d
      peptides have been explored as targeting ligands due to their superior stability
      and bioactivity in vivo. In this study, retro-inverso d-peptide (RIF7)-modified
      hyaluronic acid (HA)/bioreducible hyperbranched poly(amido amine) (RHB)/plasmid
      DNA (pDNA) ternary nanoparticles were successfully developed using the layer-by
      layer method for the CD44-positive tumour-specific delivery of short hairpin RNA
      (shRNA)-encoding pDNA through the combination of the Anxa1 (tumour vasculature)
      and CD44 (tumour cell-surface) receptors, which mediated the dual targeting. The
      potential of these newly designed nanoparticles was evaluated by examining the
      efficacy of their cellular uptake and transfection in cell monolayers, tumour
      spheroids, and malignant xenograft animal models. With negligible cytotoxicity,
      the spherical-shaped RIF7-HA/RHB/pDNA nanoparticles were the direct result of an
      electrostatic complex that had efficiently targeted CD44-positive tumour
      delivery, penetration, and cellular uptake in vitro. The nanoparticles showed
      excellent target-specific gene transfection even in the presence of serum. The in
      vivo therapeutic effect of RIF7-HA/RHB/pDNA-shRNA nanoparticle-mediated shRNA
      targeting of the Cyclin gene (shCyclin) was evaluated in tumour-bearing mice. The
      RIF7-HA/RHB/pDNA-shCyclin nanoparticles significantly increased the survival time
      of tumour-bearing mice and substantially reduced tumour growth due to their
      extremely specific tumour-targeting activity. These results suggested that the
      combination of HA and retro-inverso peptide RIF7 significantly increased the
      therapeutic effect of pDNA-shCyclin-loaded nanoparticles for CD44-positive
      tumours. Thus, RIF7-HA-mediated multi-target ternary gene vectors are an
      efficient and promising strategy for the delivery of pDNA-shRNA in the targeted
      treatment of malignant and metastatic cancers. STATEMENT OF SIGNIFICANCE:
      Although l-peptide ligands play significant roles in the active targeting of
      nanomedicine, retro-inverso d-peptides have been explored as targeting ligands
      due to their superior stability and bioactivity in vivo. Retro-inverso peptide
      RIF7 was designed as a ligand of Anxa1 receptor. The resultant peptide, RIF7,
      displayed high binding efficiency within Anxa1 receptor, which is highly
      expressed tumour vasculature cells and some tumour cells such as B16F10 and U87MG
      cells. The most important feature of RIF7 is its high stability in the blood,
      which is suitable and promising for application in vivo. Multifunctional RIF7-HA
      was then synthesized by conjugating the RIF7 peptide to HA, which was used to
      modify the surface of RHB/pDNA nanoparticles to prepare RIF7-HA/RHB/pDNA core
      shell ternary nanoparticles for the dual-targeted delivery of shRNA-encoding
      plasmids in vitro and in vivo.

PMID- 28442416
TI  - Molecular characterization and expression of interleukin-10 and interleukin-22 in
      golden pompano (Trachinotus ovatus) in response to Streptococcus agalactiae
      stimulus.
AB  - In the present study, members of the interleukin (IL)-10 family of cytokines,
      including IL-10 (TOIL-10) and IL-22 (TOIL-22) of golden pompano (Trachinotus
      ovatus), were cloned for the first time, and their expression patterns and 3D
      structures analyzed. The full-length cDNA sequences of TOIL-10 and TOIL-22
      contained open reading frames of 564 and 567 bp, respectively. TOIL-10 and TOIL
      22 shared higher homology (78%-89%) with the corresponding genes from various
      fish relative to other species (25%-34%) and contained the IL-10 family signature
      and four cysteine residues that are well conserved in other vertebrate IL-10
      members. Phylogenetic tree analysis of our sequences alongside other IL-10 family
      proteins revealed that TOIL-10 and TOIL-22 cluster together with other teleost IL
      10 and IL-22 molecules. Expression of TOIL-10 and TOIL-22 genes was ubiquitous in
      all tissues examined. The TOIL-10 gene was also highly expressed in skin, heart,
      gill, spleen, kidney, brain and liver, and lower levels were detected in
      intestine and muscle. High expression of the TOIL-22 gene was observed in gill,
      intestine, kidney, spleen, with the lowest levels in liver. TOIL-10 and TOIL-22
      were rapidly activated after SADeltaphoB immunization and significantly increased
      to peak levels at 12 h and 4 d in golden pompano kidney and spleen respectively
      following challenge. Expression in the brain reached peak levels at 4 d and 3 d
      respectively after post-immunization. Our results collectively indicate that TOIL
      10 and TOIL-22 participate in the host immune response to bacterial infection.
      Moreover, TOIL-22 plays a potentially important role in mucosal immunity.

PMID- 28442417
TI  - Cloning, expression analysis, and antibacterial propertiesof three serum amyloid
      A in common carp (Cyprinus carpio).
AB  - Three serum amyloid A (SAA) genes were identified from the common carp (Cyprinus
      carpio) by PCR and RT-PCR. Considering both direction and sequence similarity
      with mammal's orthologs, they were named CcSAA3a, CcSAA3b and CcSAA1. CcSAA3b and
      CcSAA1 are adjacent on contig LHQP01017858, suggesting that the prototype of or
      the simplest SAA multigene family have occurred in common carp. A phylogenetic
      analysis of the SAAs indicated that the fish SAAs were closer to those of
      invertebrates and Ornithorhynchus anatinus, a primitive mammal, than to mammalian
      SAAs. Quantitative real-time RT-PCR results displayed different expression
      profiles of three CcSAAs. The CcSAA3a was detected in all tested tissues, and was
      most abundant in the muscle; CcSAA3b was predominately expressed in the intestine
      and liver, and CcSAA1 in the skin. The expression level of CcSAA3a was higher
      than that of CcSAA3b and CcSAA1 in most tissues. Stimulation with Aeromonas
      hydrophila dramatically induced the expression of the three CcSAAs in all
      examined tissues, especially in the liver. Like Epinephelus coioides SAA, all of
      three rCcSAA fusion proteins could bind to both Gram-negative bacteria (A.
      hydrophila and E. coli) and Gram-positive bacterium (S. aureus), playing a role
      in the identification of bacteria. However, only rCcSAA3a showed significantly
      anti-A. hydrophila and anti-E. coli in vitro antibacterial activity assays. These
      results suggested that the three CcSAAs were in functional differentiation and
      play significant roles in the innate immunity of common carp.

PMID- 28442419
TI  - A sulfated galactans supplemented diet enhances the expression of immune genes
      and protects against Vibrio parahaemolyticus infection in shrimp.
AB  - A sulfated galactans (SG) supplemented diet was evaluated for the potential to
      stimulate immune activity in shrimp Penaeus vannamei (P. vannamei). Shrimp given
      the SG supplemented diet (0.5, 1 and 2% w/w) for 7 days showed enhanced
      expression of the downstream signaling mediator of lipopolysaccharide and beta
      1,3-glucan binding protein (LGBP) and immune related genes including p-NF-kappaB,
      IMD, IKKbeta and IKKepsilon, antimicrobial peptide PEN-4, proPO-I and II.
      Following immersion with Vibrio parahaemolyticus (V. parahaemolyticus) for 14
      days, the shrimp given the SG supplemented diet (1 and 2% w/w) showed a decrease
      in bacterial colonies and bacterial toxin gene expression, compared to shrimp
      given a normal diet, and they reached 50% mortality at day 14. However, shrimp
      given the normal diet and challenged with the bacteria reached 100% mortality at
      day 6. SG-fed shrimp increased expression of immune genes related to LGBP
      signaling at day 1 after the bacterial immersion compared to control (no
      immersion), which later decreased to control levels. Shrimp on the normal diet
      also increased expression of immune related genes at day 1 after immersion which
      however decreased below control levels by day 3. Taken together, the results
      indicate the efficacy of the SG supplemented diet to enhance the immune activity
      in shrimp which could offer protection from V. parahaemolyticus infection.

PMID- 28442418
TI  - Tlr22 structure and expression characteristic of barbel chub, Squaliobarbus
      curriculus provides insights into antiviral immunity against infection with grass
      carp reovirus.
AB  - Grass carp reovirus (GCRV) is the most virulent agent to Grass carp,
      Ctenopharyngodon idella, and causes a severe infectious disease called
      hemorrhagic disease of grass carp. Generally, barbel chub, Squaliobarbus
      curriculus, a genetically closely related species to grass carp, exhibits
      significant resistance against GCRV infection compared to grass carp. To
      investigate whether the Toll-like receptor 22 (tlr22) has got a vital role
      against the GCRV infection, the full cDNA sequence of tlr22 from barbel chub
      (Sctlr22) was cloned by RACE-PCR, and the structure and expression feature were
      studied. The complete cDNA sequence of Sctlr22 has a size of 3504 bp, encoding
      for 960 amino acid residues. Sctlr22 possesses typical structural features of the
      tlrs family, including 19 leucine rich repeats (LRRs), a transmembrane (TM) and a
      Toll/interleukin-1 receptor (TIR) domain. Phylogenetic analysis revealed that
      barbel chub Tlr22 was clustered together with the Tlr22 of grass carp (Citlr22).
      Structurally, barbel chub Tlr22 have two different structure in LRRs domain and
      TIR domain with grass carp (Susceptible to GCRV), but was similar to that of
      Danio rerio and Cyprinus carpio (Resistance to GCRV). Quantitative RT-PCR
      analysis has shown that Sctlr22 is prominently expressed in immune relevant
      tissues such as head kidney and spleen. After GCRV infection, Sctlr22 expression
      level was up-regulated in four tested tissues and the highest expression of
      Sctlr22 appeared fast and higher than Citlr22. The interferon-beta (ifn-beta)
      expression level in CIK cells over-expressing fused cDNA encoding the LRR domain
      of Sctlr22 to the transmembrane and TIR domain of Citlr22 was significantly
      higher than that cells overexpressing Citlr22 after GCRV infection. The virus
      titer was significantly reduced compared to Citlr22 over-expressing cells. These
      results suggested that Sctlr22 seems to play a vital role in the immune response
      against GCRV.

PMID- 28442420
TI  - Eggerthella lenta bacteremia in solid tumor cancer patients: Pathogen or witness
      of frailty?
AB  - Eggerthella lenta is increasingly found in patients with severe comorbidities.
      Because oncologic patients are exposed to emerging pathogens, we aimed to
      describe the factors associated with E. lenta bacteremia in this immunosuppressed
      population. Oncology patients with blood cultures positive for E. lenta were
      retrospectively recorded from 2009 to 2015. Socio-demographic and
      medical/biological data as well as potential risk factors and mortality were
      recorded and analyzed. Twenty-three patients were included. Gastro intestinal
      (GI) and gynecological cancers were reported in 12/23 (52%) and 7/23 cases (30%),
      respectively. Eleven/23 patients (48%) had metastatics lesions and 6/23 (26%) had
      peritoneal carcinomatosis. No associated tissue infection was found in 14/23
      cases (61%). Blood cultures yielded at least one other species in addition to E.
      lenta in 10/23 cases (43%). Mortality associated with E. lenta bacteremia was 22%
      (5/23). E. lenta bacteremia often occurred in patients with advanced cancer
      disease without documented infection. In most of the cases, intestinal
      obstruction and/or isolated fever were the only recorded symptoms. In these
      cases, the damages of intestinal barrier induced by the cancer and/or its
      specific treatments may be the cause of bacterial translocation.

PMID- 28442421
TI  - Distinct roles for dietary lipids and Porphyromonas gingivalis infection on
      atherosclerosis progression and the gut microbiota.
AB  - Mounting evidence in humans supports an etiological role for the microbiota in
      inflammatory atherosclerosis. Atherosclerosis is a progressive disease
      characterized by accumulation of inflammatory cells and lipids in vascular
      tissue. While retention of lipoprotein into the sub-endothelial vascular layer is
      believed to be the initiating stimulus leading to the development of
      atherosclerosis, activation of multiple pathways related to vascular inflammation
      and endothelial dysfunction sustain the process by stimulating recruitment of
      leukocytes and immune cells into the sub-endothelial layer. The Gram-negative
      oral pathogen Porphyromonas gingivalis has been associated with the development
      and acceleration of atherosclerosis in humans and these observations have been
      validated in animal models. It has been proposed that common mechanisms of immune
      signaling link stimulation by lipids and pathogens to vascular inflammation.
      Despite the common outcome of P. gingivalis and lipid feeding on atherosclerosis
      progression, we established that these pro-atherogenic stimuli induced distinct
      gene signatures in the ApoE-/- mouse model of atherosclerosis. In this study, we
      further defined the distinct roles of dietary lipids and P. gingivalis infection
      on atherosclerosis progression and the gut microbiota. We demonstrate that diet
      induced lipid lowering resulted in less atherosclerotic plaque in ApoE-/- mice
      compared to ApoE-/- mice continuously fed a Western diet. However, the effect of
      diet-induced lipid lowering on plaque accumulation was blunted by P. gingivalis
      infection. Using principal component analysis and hierarchical clustering, we
      demonstrate that dietary intervention as well as P. gingivalis infection result
      in distinct bacterial communities in fecal and cecal samples of ApoE-/- mice as
      compared to ApoE-/- mice continuously fed either a Western diet or a normal chow
      diet. Collectively, we identified distinct microbiota changes accompanying
      atherosclerotic plaque, suggesting a future avenue for investigation on the
      impact of the gut microbiota, diet, and P. gingivalis infection on
      atherosclerosis.

PMID- 28442422
TI  - Effects of low frequency rTMS treatment on brain networks for inner speech in
      patients with schizophrenia and auditory verbal hallucinations.
AB  - INTRODUCTION: Efficacy of repetitive Transcranial Magnetic Stimulation (rTMS)
      targeting the temporo-parietal junction (TPJ) for the treatment of auditory
      verbal hallucinations (AVH) remains under debate. We assessed the influence of a
      1Hz rTMS treatment on neural networks involved in a cognitive mechanism proposed
      to subserve AVH. METHODS: Patients with schizophrenia (N=24) experiencing
      medication-resistant AVH completed a 10-day 1Hz rTMS treatment. Participants were
      randomized to active stimulation of the left or bilateral TPJ, or sham
      stimulation. The effects of rTMS on neural networks were investigated with an
      inner speech task during fMRI. Changes within and between neural networks were
      analyzed using Independent Component Analysis. RESULTS: rTMS of the left and
      bilateral TPJ areas resulted in a weaker network contribution of the left
      supramarginal gyrus to the bilateral fronto-temporal network. Left-sided rTMS
      resulted in stronger network contributions of the right superior temporal gyrus
      to the auditory-sensorimotor network, right inferior gyrus to the left fronto
      parietal network, and left middle frontal gyrus to the default mode network.
      Bilateral rTMS was associated with a predominant inhibitory effect on network
      contribution. Sham stimulation showed different patterns of change compared to
      active rTMS. CONCLUSION: rTMS of the left temporo-parietal region decreased the
      contribution of the left supramarginal gyrus to the bilateral fronto-temporal
      network, which may reduce the likelihood of speech intrusions. On the other hand,
      left rTMS appeared to increase the contribution of functionally connected regions
      involved in perception, cognitive control and self-referential processing. These
      findings hint to potential neural mechanisms underlying rTMS for hallucinations
      but need corroboration in larger samples.

PMID- 28442423
TI  - SLC6A1 gene involvement in susceptibility to attention-deficit/hyperactivity
      disorder: A case-control study and gene-environment interaction.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is an early onset childhood
      neurodevelopmental disorder with an estimated heritability of approximately 76%.
      We conducted a case-control study to explore the role of the SLC6A1 gene in ADHD.
      The genotypes of eight variants were determined using Sequenom MassARRAY
      technology. The participants in the study were 302 children with ADHD and 411
      controls. ADHD symptoms were assessed using the Conners Parent Symptom
      Questionnaire. In our study, rs2944366 was consistently shown to be associated
      with the ADHD risk in the dominant model (odds ratio [OR]=0.554, 95% confidence
      interval [CI]=0.404-0.760), and nominally associated with Hyperactive index score
      (P=0.027). In addition, rs1170695 has been found to be associated with the ADHD
      risk in the addictive model (OR=1.457, 95%CI=1.173-1.809), while rs9990174 was
      associated with the Hyperactive index score (P=0.010). Intriguingly, gene
      environmental interactions analysis consistently revealed the potential
      interactions of rs1170695 with blood lead (Pmul=0.044) to modify the ADHD risk.
      Expression quantitative trait loci analysis suggested that these positive single
      nucleotide polymorphisms (SNPs) may mediate SLC6A1 gene expression. Therefore,
      our results suggest that selected SLC6A1 gene variants may have a significant
      effect on the ADHD risk.

PMID- 28442424
TI  - Thioredoxin is not a marker for treatment-resistance depression but associated
      with cognitive function: An rTMS study.
AB  - Elevated oxidative stress is known to play an important role in development of
      depression and cognitive dysfunction. To date, thioredoxin (TRX), an antioxidant
      protein, has been investigated as a marker for psychiatric disorders such as
      schizophrenia, bipolar disorder and autism but its relationship with depression
      is yet to be unknown. The aim of this study is to detect the TRX levels in
      patients with treatment-resistant depression (TRD), analyse the effect of rTMS
      (repetitive transcranial magnetic stimulation) application on TRX levels and
      display the relationship of TRX with cognitive areas. This study included 27
      treatment-resistant unipolar depression patients and 29 healthy subjects.
      Patients were evaluated by Hamilton Depression Scale (HDRS), Hamilton Anxiety
      Scale (HARS) and Montreal Cognitive Assessment (MoCA) before and after rTMS
      application. 23 of TRD patients were applied high-frequency rTMS over left DLPFC
      for 2 to 4weeks and plasma TRX levels of patients and healthy subjects were
      measured. No significant difference was determined between the TRX levels of
      patients and healthy subjects (p>0.05). After rTMS application there were
      significant decrease in severity of depression (p<0.001) and anxiety (p<0.001),
      and explicit improvement in cognitive areas (delayed memory, visual
      spatial/executive abilities and language points) (all p<0.05). No difference was
      detected in TRX levels of the patients after rTMS application (p>0.005). High
      language scores of the patients were found to be associated with high TRX levels
      (p<0.005). Our study indicates that TRX levels cannot be used as a marker for TRD
      or rTMS treatment in TRD. In spite of this TRX levels have a positive correlation
      with language functions of the patients of TRD. More extensive studies are
      required to clarify the mechanism of action of TRX and the effect of TRX on
      cognitive functions.

PMID- 28442425
TI  - Aquaporin-3 is down-regulated in jejunum villi epithelial cells during
      enterotoxigenic Escherichia coli-induced diarrhea in mice.
AB  - Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea is a complex
      pathological process, involving ion channel regulation and water efflux. While
      the mechanism underlying water efflux in ETEC-induced diarrhea is still largely
      unknown, aquaporins (AQPs) play important roles in transcellular water movement,
      but their expression profile has not been demonstrated in the murine small
      intestine. We identified AQP3 expression in the jejunum, but not the duodenum or
      ileum, using reverse transcription PCR and western blotting. Immunohistochemistry
      showed that AQP3 localized to the jejunum villi epithelial cells. Using an ETEC
      induced murine diarrhea model, we demonstrated that both AQP3 mRNA expression and
      protein concentration in the jejunum were gradually but significantly decreased
      over 7 d compared with controls. These results suggested impaired water influx
      also plays an important role in ETEC-induced diarrhea.

PMID- 28442426
TI  - Identification of a wza-like gene involved in capsule biosynthesis, pathogenicity
      and biofilm formation in Riemerella anatipestifer.
AB  - Duck infectious serositis is the most serious bacterial disease of ducks. It is
      caused by Riemerella anatipestifer (RA) infection. The capsule plays an important
      role in virulence of many pathogenic bacteria. In addition, the capsule has some
      key biological features. However, few studies have explored the characteristics
      of the RA capsule. In this study, we mainly constructed a capsular mutants of RA
      by inactivating the wza gene using homologous recombination. We found that the
      mutant was failed to produce a capsule layer. The mutant was less resistant to
      killing by the host complement or by desiccation and oxidative stress.
      Furthermore, the mutant strain was more hydrophobic, more able to auto-aggregate
      and underwent increased biofilm formation. Moreover, the mutant was less virulent
      than the wild-type in vivo studies. In summary, we found that the RA capsule was
      involved in the desiccation and oxidative stress, surface hydrophobicity,
      complement-mediated killing, biofilm formation, and virulence.

PMID- 28442427
TI  - Neglected antibacterial activity of ethylene glycol as a common solvent.
AB  - For the first time, the antibacterial activity of ethylene glycol (EG), a routine
      frequently used solvent against Escherichia coli (E. coli) bacterium, was
      assessed. The antibacterial activity of EG against E. coli was measured using
      colony counting and broth turbidity assays. The influence of EG concentration
      (1.5-25.0%v/v) and exposure time on the growth of E. coli was investigated. By
      increasing EG concentration, its antibacterial activity against E. coli increased
      so that for 24.0% of EG, the bacteria growth was totally inhibited within 4 h.
      The MIC and MBC values of EG are 18.0 and 24.0%v/v, respectively. Since the ratio
      of MBC to MIC is less than four, EG acts as a bactericidal agent. Also, a model
      for the slopes of the linear part of the growth curves was proposed. The SEM
      images of bacteria cells before and after exposure to EG show that most E. coli
      were seriously distorted.

PMID- 28442429
TI  - Woodland features determining home range size of roe deer.
AB  - Use of ecotones by ungulates may be mediated by their movements between main
      feeding areas and woodland, where they locate their shelter. The roe deer
      Capreolus capreolus has been termed as a woodland species, although we suggest
      that it did not evolve as a forest ungulate, but depending on forest glades. Roe
      deer feed on a wide range of vegetal species, although their diet is mainly
      dominated by woody plants. Our study was carried out in a fragmented area covered
      with small forest patches of Mediterranean "macchia" scrubwood, interspersed in
      an agricultural matrix. Aim of our study has been to test how ranging movements
      of roe deer are influenced by landscape heterogeneity and to evaluate which
      features of woodland affect home range size. Radio-locations of 22 female and 12
      male adult roe deer, monitored for three years, were used to assess home range
      size. A linear mixed model was fitted to investigate variation in home range size
      according to eleven spatial parameters estimated to describe home range size and
      composition. Throughout the year, no significant difference was found between
      home range sizes of males (median: 16.70ha, Q1-Q3: 13.20-31.60ha) and females
      (median: 23.52ha, Q1-Q3: 13.30-44.00ha: lme: F=0.9; P=0.35). Habitat density,
      edge density, percentage of woodland within home range and woodland structure
      determined home range size. Home ranges with few habitat types and a small amount
      of wood were large, while roe deer occupied small home ranges when habitat
      density was high and when a high proportion of wood was concentrated in a single
      large patch. Woodland covered a mean+/-SE of 36.2+/-17.9% in each home range. In
      conclusion, roe deer seem to be particularly well adapted to live in human
      transformed, peripheral habitats, e.g. farmlands, as long as a minimum quantity
      of woodland is included within their HR.

PMID- 28442430
TI  - Design and purification of active truncated phosphoinositide 3-kinase gamma
      protein constructs for structural studies.
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) is a lipid kinase that plays a
      crucial role in cell migration, chemotaxis, oxidative burst and myocardial
      contractility. It is activated downstream of G protein-coupled receptors (GPCRs)
      and small GTPases of Ras superfamily. PI3Kgamma is a heterodimer composed of a
      catalytic and a regulatory subunit that is expressed mostly in hematopoietic
      cells and in the heart. Although it has attracted a lot of attention because of
      its link with tumor inflammation and heart diseases, its regulation is still not
      fully understood. This can be attributed to the absence of high-resolution
      structural details of the PI3Kgamma heterodimer. Here we describe the design and
      purification of PI3Kgamma constructs where flexible loops in the regulatory
      subunit have been removed based on structural information obtained by
      hydrogen/deuterium exchange - mass spectrometry (HDX-MS). The soluble constructs
      retain both basal activity and sensitivity to GPCR stimulation, and are thus an
      optimal tool to further explore their regulation using a structure-based
      approach.

PMID- 28442428
TI  - Rapamycin modulation of p70 S6 kinase signaling inhibits Rift Valley fever virus
      pathogenesis.
AB  - Despite over 60 years of research on antiviral drugs, very few are FDA approved
      to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod
      borne virus that causes hemorrhagic fever in severe cases, currently lacks
      effective treatments. Existing as obligate intracellular parasites, viruses have
      evolved to manipulate host cell signaling pathways to meet their replication
      needs. Specifically, translation modulation is often necessary for viruses to
      establish infection in their host. Here we demonstrated phosphorylation of p70 S6
      kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through
      western blot analysis and in a mouse model of infection through reverse phase
      protein microarrays (RPPA). Inhibition of p70 S6 kinase through rapamycin
      treatment reduced viral titers in vitro and increased survival and mitigated
      clinical disease in RVFV challenged mice. Additionally, the phosphorylation of
      p70 S6 kinase was decreased following rapamycin treatment in vivo. Collectively
      these data demonstrate modulating p70 S6 kinase can be an effective antiviral
      strategy.

PMID- 28442431
TI  - Reducing isoform complexity of human tetraspanins by optimized expression in
      Dictyostelium discoideum enables high-throughput functional read-out.
AB  - The human tetraspanin family of scaffold proteins comprises 33 isoforms. Being
      integral membrane proteins, they organize a so-called tetraspanin web via
      homomeric and heteromeric protein-protein interactions with integrins,
      immunoglobulins, growth factors, receptor tyrosine kinases, proteases, signaling
      proteins, and viral capsid proteins. Tetraspanins promote cellular effects, such
      as adhesion, migration, invasion, signaling, membrane fusion, protein
      trafficking, cancer progression, and infections. The ubiquitous expression of
      multiple tetraspanin isoforms and partner proteins hampers specific interaction
      studies. Here, we evaluated Dictyostelium discoideum as a non-mammalian
      expression system for human tetraspanins. Using high-content imaging we
      quantified tetraspanins in D. discoideum via fusion with green fluorescent
      protein. Three human tetraspanins, CD9, CD81, and CD151, served as test cases for
      which optimizations were carried out. We swapped the GFP domain between the N-
      and C-termini, added a Kozak sequence, and partially or fully adapted of the
      codon usage. This way, CD81 and CD151 were successfully produced. A conformation
      specific antibody further confirmed correct folding of CD81 and flow cytometry
      indicated an intracellular localization. Based on these data, we envision a D.
      discoideum-based co-expression platform with human partner proteins for studying
      tetraspanin interactions and their selective druggability on a large scale
      without the interference of endogenous human proteins.

PMID- 28442432
TI  - Fibre diffraction studies of biological macromolecules.
AB  - Two fundamental structures in molecular biology, DNA and the alpha-helix, were
      determined using X-ray fibre diffraction data, and yet fibre diffraction occupies
      an obscure niche in structural biology. Relatively few structures are appropriate
      for the technique, and it seldom supplies data of the quality common in protein
      crystallography; however, it has proven indispensable in some cases. Here we
      outline some aspects of helix diffraction mathematics, and then illustrate the
      application of fibre diffraction by three case studies: DNA, filamentous
      bacterial viruses, and bacterial pili. These examples are illustrative, not
      exhaustive, and reviews of other important structures such as plant viruses,
      polysaccharides and amyloids are also cited, as appropriate. Finally we describe
      in more detail the methods currently used to obtain and analyze fibre diffraction
      patterns of biological macromolecules, to give a technique-oriented tutorial
      which may be useful to researchers who find that they require fibre diffraction
      for their work.

PMID- 28442433
TI  - Electronic health record as a research tool: Frequency of exposure to targeted
      clinical problems and health care providers' clinical proficiency.
AB  - OBJECTIVES: The Electronic Health Record (EHR) could provide insight into
      possible decay in health care providers' (HCP) clinical knowledge and cognitive
      performance. Analyses of the contributions of variables such as frequency of
      exposure to targeted clinical problems could inform the development and testing
      of appropriate individualized interventions to mitigate these threats to quality
      and safety of care. MATERIALS/METHODS: Nine targeted clinical problems (TCP) were
      selected for further study, and de-identified, aggregated study data were
      obtained for one calendar year. Task analysis interviews of subspecialty
      physicians defined optimal management of each TCP and guided specification of
      quality of care metrics that could be extracted from the EHR. The Delta-t
      statistic, days since the provider's prior encounter with a given TCP, quantified
      frequency of exposure. RESULTS: Frequency of patient encounters ranged from 1566
      to 220,774 visits across conditions. Mean Delta-t ranged from 1.72days to
      30.79days. Maximum Delta-t ranged from 285 to 497days. The distribution of Delta
      t for the TCPs generally fit a Gamma distribution (P<0.001), indicating that
      Delta-t conforms to a Poisson process. A quality of care metric derived for each
      TCP declined progressively with increasing Delta-t for 8 of the 9 TCPs, affirming
      that knowledge decay was detectable from EHR data. DISCUSSION/CONCLUSIONS: This
      project demonstrates the utility of the EHR as a research tool in studies of
      health care delivery in association with frequency of exposure of HCPs to TCPs.
      Subsequent steps in our research include multivariate modeling of clinical
      knowledge decay and randomized trials of pertinent preventive interventions.

PMID- 28442434
TI  - Clinical code set engineering for reusing EHR data for research: A review.
AB  - INTRODUCTION: The construction of reliable, reusable clinical code sets is
      essential when re-using Electronic Health Record (EHR) data for research. Yet
      code set definitions are rarely transparent and their sharing is almost non
      existent. There is a lack of methodological standards for the management
      (construction, sharing, revision and reuse) of clinical code sets which needs to
      be addressed to ensure the reliability and credibility of studies which use code
      sets. OBJECTIVE: To review methodological literature on the management of sets of
      clinical codes used in research on clinical databases and to provide a list of
      best practice recommendations for future studies and software tools. METHODS: We
      performed an exhaustive search for methodological papers about clinical code set
      engineering for re-using EHR data in research. This was supplemented with papers
      identified by snowball sampling. In addition, a list of e-phenotyping systems was
      constructed by merging references from several systematic reviews on this topic,
      and the processes adopted by those systems for code set management was reviewed.
      RESULTS: Thirty methodological papers were reviewed. Common approaches included:
      creating an initial list of synonyms for the condition of interest (n=20); making
      use of the hierarchical nature of coding terminologies during searching (n=23);
      reviewing sets with clinician input (n=20); and reusing and updating an existing
      code set (n=20). Several open source software tools (n=3) were discovered.
      DISCUSSION: There is a need for software tools that enable users to easily and
      quickly create, revise, extend, review and share code sets and we provide a list
      of recommendations for their design and implementation. CONCLUSION: Research re
      using EHR data could be improved through the further development, more widespread
      use and routine reporting of the methods by which clinical codes were selected.

PMID- 28442435
TI  - Effectiveness of rotavirus pentavalent vaccine under a universal immunization
      programme in Israel, 2011-2015: a case-control study.
AB  - OBJECTIVES: The use of rotavirus pentavalent vaccine (RotaTeq(r)) as a sole
      vaccine within rotavirus universal immunization programmes remains limited. We
      examined the effectiveness of RotaTeq in preventing rotavirus gastroenteritis
      (RVGE) hospitalization in Israel, after the introduction of universal
      immunization against the disease. METHODS: A test-negative case-control study
      included age-eligible children for universal RotaTeq immunization (aged 2-59
      months, born in 2011-2015). Cases (n = 98) were patients who tested positive for
      rotavirus by immunochromatography; those who tested negative (n = 628) comprised
      the control group. Information on rotavirus immunization history was obtained
      through linkage with a national immunization registry. Vaccination status was
      compared between cases and controls, adjusted odds ratios (aORs) were obtained
      from logistic regression models, and vaccine effectiveness calculated as (1 -
      aOR)*100. RESULTS: Immunization with RotaTeq was less frequent in RVGE cases
      (73.5%) than in controls (90.1%), p < 0.001; this association persisted after
      controlling for potential confounders. Effectiveness of the complete vaccine
      series was estimated at 77% (95% confidence interval (CI): 49-90) in children
      aged 6-59 months, and 86% (95% CI: 65-94) in children aged 6-23 months; whereas
      for the incomplete series, the respective estimates were 72% (95% CI: 28-89) and
      75% (95% CI: 30-91). Vaccine effectiveness was estimated at 79% (95% CI: 45-92)
      against G1P[8]-associated RVGE hospitalizations and 69% (95% CI: 11-89) against
      other genotype-RVGE hospitalizations. CONCLUSIONS: High effectiveness of RotaTeq
      as the sole rotavirus vaccine in a universal immunization programme was
      demonstrated in a high-income country. Although partial vaccination conferred
      protection, completing the vaccine series is warranted to maximize the benefit.

PMID- 28442436
TI  - "Predictors of failure after single faecal microbiota transplantation in patients
      with recurrent Clostridium difficile infection: results from a three-year cohort
      study"; methodological issues.

PMID- 28442437
TI  - Characterization of enterotoxigenic Escherichia coli strains isolated from the
      massive multi-pathogen gastroenteritis outbreak in the Antofagasta region
      following the Chilean earthquake, 2010.
AB  - In March 2010, a massive outbreak of gastroenteritis started in the region of
      Antofagasta (northern Chile). The outbreak was mainly attributed to Norovirus
      genogroup II although ETEC strains were also isolated with high frequency from
      clinical samples. We review this outbreak and determined that ETEC was an
      underestimated etiologic agent.

PMID- 28442438
TI  - Dorsal fin development in flounder, Paralichthys olivaceus: Bud formation and its
      cellular origin.
AB  - The development of the median fin has not been investigated extensively in
      teleosts, although in other fishes it has been proposed that it involves the same
      genetic programs operating in the paired appendages. Adult median fins develop
      from the larval bud; therefore an investigation of fin bud formation and its
      cellular origin is essential to understanding the maturation mechanisms. In
      Paralichthys olivaceus, skeletogenesis proceeds from an anterior to posterior
      direction providing a good opportunity to study the formation of dorsal fin bud.
      An apical ectodermal ridge appeared at the basal stratum of the presumptive
      dorsal fin was first observed at 3 days post hatching. Then the apical ectodermal
      fold formed as the bud outgrew in 6 days post-hatch larvae. The bud continued to
      grow, breaking through the dorsal fin fold in 9 days post-hatch larvae. At 13
      days post-hatch, the bud grew beyond the edge of the fin fold and formed into the
      four future rays. Molecular markers of cell type showed the existence of neural
      crest cells, scleroblasts and sclerotomes in the dorsal fin bud. The earliest
      gene expression in the dorsal fin bud was Hoxd10 at 3 days post-hatch larvae,
      then Hoxd9, Hoxd11 and Hoxd12. This indicates Hoxd10 might be a candidate
      molecular marker of the bud formation site. Some key molecular markers for paired
      appendage development, such as FGF8, Wnt7, and Shh were expressed at the apical
      ectodermal ridge and later the apical ectodermal fold. Moreover, the form of the
      dorsal fin bud could be inhibited by Hh pathway inhibitor, further indicating
      that common basic molecular mechanisms might be utilized by median fins.

PMID- 28442439
TI  - Marshall-Smith syndrome: Novel pathogenic variant and previously unreported
      associations with precocious puberty and aortic root dilatation.
AB  - Marshall-Smith Syndrome (MRSHSS) is a very rare genetic disorder characterized by
      failure to thrive and characteristic dysmorphic features associated with
      accelerated osseous maturation. We present a nine-year-old girl who was diagnosed
      with MRSHSS based on characteristic clinical features supported by the
      identification of a novel de novo pathogenic variant in the NFIX gene. The
      patient also presented with precocious puberty diagnosed at five years of age and
      had an abnormal GnRH stimulation test indicative of central precocious puberty.
      Central precocious puberty has not been described in association with MRSHSS
      previously in the medical literature and broadens our knowledge of the natural
      history of MRSHSS. The causes of advanced bone age in this syndrome are also
      reviewed. Additionally, the patient showed progressive dilatation of the aortic
      root. Although connective tissue abnormalities have been described in association
      with MRSHSS, aortic root dilatation has not. Understanding the mechanism of
      comorbidities such as advanced bone age and aortic root dilatation in MRSHSS
      patients enables future development of anticipatory guidance, preventative care
      measures, and treatment guidelines.

PMID- 28442440
TI  - Impact of dose and surface features on plasmatic and liver concentrations of
      biodegradable polymeric nanocapsules.
AB  - The effect of polymeric nanocapsule dose on plasmatic and liver concentrations
      20min after intravenous administration in mice was evaluated. Nanocapsules were
      prepared with different polymers, namely, poly(D,L-lactide) (PLA), polyethylene
      glycol-block-poly(D,L-lactide) (PLA-PEG), and PLA with chitosan (PLA-Cs) and
      compared with a nanoemulsion. These formulations were labelled with a
      phthalocyanine dye for fluorescent detection. The nanostructures had narrow size
      distributions upon separation by asymmetric flow field flow fractionation with
      static and dynamic light scattering detection, with average hydrodynamic
      diameters in the 130-300nm range, negative zeta potentials, except PLA-Cs
      nanocapsules, which had a positive zeta potential. Flow cytometry revealed uptake
      mostly by monocytes and neutrophils in mice and human blood. PLA nanocapsules and
      the nanoemulsion showed dose-dependent plasma concentrations, where the
      percentage of plasmatic fluorescence increased with increasing administered dose.
      In contrast, PLA-PEG nanocapsules led to a dose-independent plasmatic profile.
      PLA-Cs nanocapsules showed the lowest plasmatic and liver levels of fluorescence
      at all administered doses and significant intravenous toxicity in mice. This work
      demonstrates the importance of considering the nanocarrier dose when evaluating
      pharmacokinetic and biodistribution data and emphasizes the role of surface
      features in determining the plasmatic and liver concentrations of a poorly
      soluble lipophilic encapsulated compound.

PMID- 28442441
TI  - Aspergillus flavus aswA, a gene homolog of Aspergillus nidulans oefC, regulates
      sclerotial development and biosynthesis of sclerotium-associated secondary
      metabolites.
AB  - Aspergillus flavus aswA (AFLA_085170) is a gene encoding a Zn(II)2Cys6 DNA
      binding domain and a transcriptional activation domain, DUF3468. Disruption of
      aswA yielded strains that made a truncated gene transcript and generated a fungus
      that produced a greatly increased number of sclerotia. These sclerotia were odd
      shaped and non-pigmented (white) and different from oval and pigmented (dark
      brown to black) mature sclerotia. Transcriptomic analysis of the DeltaaswA strain
      grown on potato dextrose agar plates and Wickerham agar plates showed that
      expression of clustering genes involved in the biosynthesis of three sclerotium
      associated secondary metabolites was down-regulated. These included gene clusters
      of asparasone, aflatrem, and aflavarin. In contrast, those of aflatoxin,
      cyclopiazonic acid and kojic acid were not affected. Metabolite analyses
      confirmed that the non-pigmented sclerotia contained aflatoxin and cyclopiazonic
      acid but not other aforementioned metabolites, three asparasone analogs and
      dihydroxyaflavinine commonly present in mature sclerotia. Impairment in aswA gene
      function stalls normal sclerotial development, which in turn prevents
      biosynthesis and accumulation of sclerotium-specific metabolites.

PMID- 28442442
TI  - Role of Muller cell cytochrome P450 2c44 in murine retinal angiogenesis.
AB  - Polyunsaturated fatty acids (PUFA) and their cytochrome P450 (CYP450) metabolites
      have been linked to angiogenesis and vessel homeostasis. However, the role of
      individual CYP isoforms and their endogenous metabolites in those processes are
      not clear. Here, we focused on the role of Cyp2c44 in postnatal retinal
      angiogenesis and report that Cyp2c44 is highly expressed in Muller glial cells in
      the retina. The constitutive as well as inducible postnatal genetic deletion of
      Cyp2c44 resulted in an increased vessel network density without affecting vessel
      radial expansion during the first postnatal week. This phenotype was associated
      with an increased endothelial cell proliferation and attenuated Notch signaling.
      LC-MS/MS analyses revealed that levels of hydroxydocosahexaenoic acids (HDHA),
      i.e., 10-, 17- and 20-HDHA were significantly elevated in retinas from 5day old
      Cyp2c44-/- mice compared to their wild-type littermates. Enzymatic activity
      assays revealed that HDHAs were potential substrates for Cyp2c44 which could
      account for the increased levels of HDHAs in retinas from Cyp2c44-/- mice. These
      data indicate that Cyp2c44 is expressed in the murine retina and, like the
      soluble epoxide hydrolase, is expressed in Muller glia cells. The enhanced
      endothelial cell proliferation and Notch inhibition seen in retinas from Cyp2c44
      deficient mice indicate a role for Cyp2c44-derived lipid mediators in
      physiological angiogenesis.

PMID- 28442443
TI  - Real-time imaging of mechanically and chemically induced ATP release in human
      lung fibroblasts.
AB  - Extracellular adenosine 5'-triphosphate (ATP) acts as an inflammatory mediator of
      pulmonary fibrosis. We investigated the effects of mechanical and chemical
      stimuli on ATP release from primary normal human lung fibroblasts. We visualized
      the ATP release from fibroblasts in real time using a luminescence imaging system
      while acquiring differential interference contrast cell images with infrared
      optics. Immediately following a single uniaxial stretch for 1s, ATP was released
      from a certain population of cells and spread to surrounding spaces. Hypotonic
      stress, which causes plasma membrane stretching, also induced the ATP release.
      Compared with the effects of mechanical stretch, ATP-induced release sites were
      homogeneously distributed. In contrast to the effects of mechanical stimuli,
      application of platelet-derived growth factor caused ATP release from small
      numbers of the cells. Our real-time ATP imaging demonstrates that there is a
      heterogeneous nature of ATP release from lung fibroblasts in response to
      mechanical and chemical stimuli.

PMID- 28442444
TI  - Hydrogen sulfide ameliorates prenatal cigarette smoke exposure-induced impairment
      of respiratory responses to hypercapnia in neonatal rats.
AB  - The present study was designed to investigate whether H2S could improve the
      respiratory responses to hypercapnia blunted by prenatal CSE in neonatal rats in
      vivo. Respiratory activities were recorded with head-out body plethysmography.
      The results showed that during baseline, respiratory frequency (FR), tidal volume
      (VT) and minute ventilation (VE) were similar among tested groups; frequency of
      spontaneous apnea (FSA), not post-sigh apnea (FPA), was significantly elevated by
      prenatal CSE. During hypercapnia, the increases in FR and VE were significantly
      reduced, but VT was not markedly different, in CSE group; both FSA and FPA were
      decreased, although FSA remained higher in CSE group. All the aforementioned
      effects induced by CSE on respiratory activities were relieved by NaHS (donor of
      H2S, 56MUmol/kg by intraperitoneal injection). These data indicate that H2S could
      ameliorate the disruption of respiratory responses to hypercapnia induced by
      prenatal CSE in neonatal rats.

PMID- 28442445
TI  - Cyclic mechanical stretch-induced oxidative stress occurs via a NOX-dependent
      mechanism in type II alveolar epithelial cells.
AB  - Cyclic mechanical stretching (CMS) of the alveolar epithelium is thought to
      contribute to alveolar epithelial injury through an increase in oxidative stress.
      The aim of this study was to investigate the mechanisms of CMS-induced oxidative
      stress in alveolar epithelial cells (AECs). A549 cells were subjected to CMS, and
      the levels of 8-isoprostane and 3-nytrotyrosine were measured. Twenty-four hours
      of CMS induced a significant increase in the levels of 8-isoprostane and 3
      nytrotyrosine. Although CMS did not increase the xanthine oxidase activity or the
      mitochondrial production of reactive oxygen species, it upregulated the
      expression of nicotine adenine dinucleotide phosphate oxidase (NOX) 2, 4, 5 and
      DUOX2. The NOX inhibitors DPI and GKT137831 significantly attenuated CMS-induced
      oxidative stress. Furthermore, the measurement of annexin V/propidium iodide by
      flow cytometry showed that CMS induced late-phase apoptosis/necrosis, which was
      also attenuated by both DPI and GKT137831. These data suggest that CMS mainly
      induces oxidative stress, which may lead to cell injury by activating NOX in
      AECs.

PMID- 28442446
TI  - Proteomic and transcriptomic analysis of saliva components from the hematophagous
      reduviid Triatoma pallidipennis.
AB  - : Species belonging to the Triatominae subfamily are commonly associated with
      Chagas disease, as they are potential vectors of the parasite Trypanosoma cruzi.
      However, their saliva contains a cocktail of diverse anti-hemostatic proteins
      that prevent blood coagulation, vasodilation and platelet aggregation of blood;
      components with indisputable therapeutic potential. We performed a transcriptomic
      and proteomic analyses of salivary glands and protein spots from 2DE gels of
      milked saliva, respectively, from the Mexican Triatoma pallidipennis. Massive
      sequencing techniques were used to reveal this protein diversity. A total of 78
      out of 233 transcripts were identified as proteins in the saliva, divided among
      43 of 55 spots from 2DE gels of saliva, identified by LC-MS/MS analysis. Some of
      the annotated transcripts putatively code for anti-hemostatic proteins, which
      share sequence similarities with proteins previously described for South American
      triatomines. The most abundant as well as diverse transcripts and proteins in the
      saliva were the anti-hemostatic triabins. For the first time, a transcriptomic
      analysis uncovered other unrelated but relevant components in triatomines,
      including antimicrobial and thrombolytic polypeptides. Likewise, unique proteins
      such as the angiotensin-converting enzyme were identified not just in the
      salivary gland transcriptome but also at saliva proteome of this North American
      bloodsucking insect. BIOLOGICAL SIGNIFICANCE: This manuscript is the first report
      of the correlation between proteome and transcriptome of Triatoma pallidipennis,
      which shows for the first time the presence of proteins in this insect that have
      not been characterized in other species of this family. This information
      contributes to a better understanding of the multiple host defense mechanisms
      that are being affected at the moment of blood ingestion by the insect.
      Furthermore, this report gives a repertoire of possible therapeutic proteins.

PMID- 28442447
TI  - Detailed two-dimensional gel proteomic mapping of the feces of the house dust
      mite Dermatophagoides pteronyssinus and comparison with D. farinae: Reduced
      trypsin protease content in D. pteronyssinus and different isoforms.
AB  - : Major domestic mite allergens are present in feces. We present a detailed 2D-E
      MS/MS proteomic analysis of the Dermatophagoides pteronyssinus feces. Precise
      cultivation yielded a pure fecal extract. We detected differences in fecal
      allergens/digestive enzymes between D. pteronyssinus and D. farinae using 2D-E
      fingerprinting, including unique information on species-specific protease
      isoforms. Proteomic analysis was performed by 2D-E coupled with MALDI-TOF/TOF
      identification. The species-specific differences in the fecal extracts of the
      mites were attributed to trypsin-like proteases known as group 3 allergens. In D.
      farinae, Der f 3 exhibited high abundance with a pI similar (acidic) to that of
      the cysteine protease Der f 1 and the chymotrypsin protease Der f 6, whereas in
      D. pteronyssinus, Der p 3 was rarely detected and exhibited low abundance only at
      basic pI. Moreover, Der p 9 was detected at a pI of ~ 10, in contrast to Der p 1
      and Der p 6, suggesting different compartmentalization in the body. Overall, in
      D. pteronyssinus feces, allergens of groups 1, 2, 6, and 15 were quantitatively
      similar to those of D. farinae with the exception of the group 3 and 9 allergens.
      This work provides novel insights into mite-defecated proteins/digestive enzymes,
      which are important allergens. SIGNIFICANCE: Millions of people are affected by
      allergy and asthma, and their number is growing. In homes, the major triggers of
      allergy and asthma are the house dust mites Dermatophagoides farinae and D.
      pteronyssinus, and a clear understanding of the development of diseases caused by
      these mites is needed. The major sources of mite allergens are their feces, which
      are deposited in the environment and are easily inhaled as part of aeroplankton.
      However, descriptions of and comparisons between the major fecal allergens of
      these two mites are lacking. This study shows that similar group 1 (cysteine
      protease), 2 (NPC2 family), 6 (chymotrypsin) and 15 (chitinase-like) allergens
      are present in the feces of these two mite species, as determined by 2D-E
      mapping, whereas group 3 (trypsin) and 9 (collagenolytic protease) allergens in
      the feces of the two species are different. The results provide unique MS/MS
      mapped fingerprints of mite species-specific isoforms in feces. The presence of
      ubiquitin in mite feces suggests that these proteins participate in the post
      translational modification of fecal proteins. The findings are essential for
      understanding differences between D. farinae and D. pteronyssinus with respect to
      immunoreactivity, protease activation mechanisms, association with microbes, and
      food utilization.

PMID- 28442448
TI  - Phosphotyrosine-based-phosphoproteomics scaled-down to biopsy level for analysis
      of individual tumor biology and treatment selection.
AB  - : Mass spectrometry-based phosphoproteomics of cancer cell and tissue lysates
      provides insight in aberrantly activated signaling pathways and potential drug
      targets. For improved understanding of individual patient's tumor biology and to
      allow selection of tyrosine kinase inhibitors in individual patients,
      phosphoproteomics of small clinical samples should be feasible and reproducible.
      We aimed to scale down a pTyr-phosphopeptide enrichment protocol to biopsy-level
      protein input and assess reproducibility and applicability to tumor needle
      biopsies. To this end, phosphopeptide immunoprecipitation using anti
      phosphotyrosine beads was performed using 10, 5 and 1mg protein input from
      lysates of colorectal cancer (CRC) cell line HCT116. Multiple needle biopsies
      from 7 human CRC resection specimens were analyzed at the 1mg-level. The total
      number of phosphopeptides captured and detected by LC-MS/MS ranged from 681 at
      10mg input to 471 at 1mg HCT116 protein. ID-reproducibility ranged from 60.5% at
      10mg to 43.9% at 1mg. Per 1mg-level biopsy sample, >200 phosphopeptides were
      identified with 57% ID-reproducibility between paired tumor biopsies.
      Unsupervised analysis clustered biopsies from individual patients together and
      revealed known and potential therapeutic targets. SIGNIFICANCE: This study
      demonstrates the feasibility of label-free pTyr-phosphoproteomics at the tumor
      biopsy level based on reproducible analyses using 1mg of protein input. The
      considerable number of identified phosphopeptides at this level is attributed to
      an effective down-scaled immuno-affinity protocol as well as to the application
      of ID propagation in the data processing and analysis steps. Unsupervised cluster
      analysis reveals patient-specific profiles. Together, these findings pave the way
      for clinical trials in which pTyr-phosphoproteomics will be performed on pre- and
      on-treatment biopsies. Such studies will improve our understanding of individual
      tumor biology and may enable future pTyr-phosphoproteomics-based personalized
      medicine.

PMID- 28442449
TI  - Comparative proteomics of hydatid fluids from two Echinococcus multilocularis
      isolates.
AB  - : The hydatid fluid (HF) that fills Echinococcus multilocularis metacestode
      vesicles is a complex mixture of proteins from both parasite and host origin.
      Here, a LC-MS/MS approach was used to compare the HF composition of E.
      multilocularis H95 and G8065 isolates (EmH95 and EmG8065, respectively), which
      present differences in terms of growth and fertility. Overall, 446 unique
      proteins were identified, 392 of which (88%) were from parasite origin and 54
      from culture medium. At least 256 of parasite proteins were sample exclusive, and
      82 of the 136 shared proteins presented differential abundance between E.
      multilocularis isolates. The parasite's protein repertoires in EmH95 and EmG8065
      HF samples presented qualitative and quantitative differences involving antigens,
      signaling proteins, proteolytic enzymes, protease inhibitors and chaperones,
      highlighting intraspecific singularities that could be correlated to biological
      features of each isolate. The repertoire of medium proteins found in the HF was
      also differential between isolates, and the relevance of the HF exogenous protein
      content for the parasite's biology is discussed. The repertoires of identified
      proteins also provided potential molecular markers for important biological
      features, such as parasite growth rate and fertility, as well potential protein
      targets for the development of novel diagnostic and treatment strategies for
      alveolar echinococcosis. BIOLOGICAL SIGNIFICANCE: E. multilocularis metacestode
      infection of mammal hosts involve complex interactions mediated by
      excretory/secretory (ES) products. The hydatid fluid (HF) that fills the E.
      multilocularis metacestode vesicles contains complex repertoires of parasite ES
      products and host proteins that mediate important molecular interactions
      determinant for parasite survival and development, and, consequently, to the
      infection outcome. HF has been also extensively reported as the main source of
      proteins for the immunodiagnosis of echinococcosis. The performed proteomic
      analysis provided a comprehensive profiling of the HF protein composition of two
      E. multilocularis isolates. This allowed us to identify proteins of both parasite
      and exogenous (medium) origin, many of which present significant differential
      abundances between parasite isolates and may correlate to their differential
      biological features, including fertility and growth rate.

PMID- 28442451
TI  - Using Mobile Phones to Collect Patient Data: Lessons Learned From the SIMPle
      Study.
AB  - BACKGROUND: Mobile phones offer new opportunities to efficiently and
      interactively collect real-time data from patients with acute illnesses, such as
      urinary tract infections (UTIs). One of the main benefits of using mobile data
      collection methods is automated data upload, which can reduce the chance of data
      loss, an issue when using other data collection methods such as paper-based
      surveys. OBJECTIVE: The aim was to explore differences in collecting data from
      patients with UTI using text messaging, a mobile phone app (UTI diary), and an
      online survey. This paper provides lessons learned from integrating mobile data
      collection into a randomized controlled trial. METHODS: Participants included UTI
      patients consulting in general practices that were participating in the
      Supporting the Improvement and Management of UTI (SIMPle) study. SIMPle was
      designed to improve prescribing antimicrobial therapies for UTI in the community.
      Patients were invited to reply to questions regarding their UTI either via a
      prospective text message survey, a mobile phone app (UTI diary), or a
      retrospective online survey. Data were collected from 329 patients who opted in
      to the text message survey, 71 UTI patients through the mobile phone UTI symptom
      diary app, and 91 online survey participants. RESULTS: The age profile of UTI
      diary app users was younger than that of the text message and online survey
      users. The largest dropout for both the text message survey respondents and UTI
      diary app users was after the initial opt-in message; once the participants
      completed question 1 of the text message survey or day 2 in the UTI diary app,
      they were more likely to respond to the remaining questions/days. CONCLUSIONS:
      This feasibility study highlights the potential of using mobile data collection
      methods to capture patient data. As well as improving the efficiency of data
      collection, these novel approaches highlight the advantage of collecting data in
      real time across multiple time points. There was little variation in the number
      of patients responding between text message survey, UTI diary, and online survey,
      but more patients participated in the text message survey than the UTI diary app.
      The choice between designing a text message survey or UTI diary app will depend
      on the age profile of patients and the type of information the researchers'
      desire. TRIAL REGISTRATION: ClinicalTrials.gov NCT01913860;
      https://clinicaltrials.gov/ct2/show/NCT01913860 (Archived by WebCite at
      http://www.webcitation.org/6pfgCztgT).

PMID- 28442450
TI  - Implementing an Internet-Delivered Skin Cancer Genetic Testing Intervention to
      Improve Sun Protection Behavior in a Diverse Population: Protocol for a
      Randomized Controlled Trial.
AB  - BACKGROUND: Limited translational genomic research currently exists to guide the
      availability, comprehension, and appropriate use of personalized genomics in
      diverse general population subgroups. Melanoma skin cancers are preventable,
      curable, common in the general population, and disproportionately increasing in
      Hispanics. OBJECTIVE: Variants in the melanocortin-1 receptor (MC1R) gene are
      present in approximately 50% of the population, are major factors in determining
      sun sensitivity, and confer a 2-to-3-fold increase in melanoma risk in the
      general population, even in populations with darker skin. Therefore, feedback
      regarding MC1R risk status may raise risk awareness and protective behavior in
      the general population. METHODS: We are conducting a randomized controlled trial
      examining Internet presentation of the risks and benefits of personalized genomic
      testing for MC1R gene variants that are associated with increased melanoma risk.
      We will enroll a total of 885 participants (462 participants are currently
      enrolled), who will be randomized 6:1 to personalized genomic testing for
      melanoma risk versus waiting list control. Control participants will be offered
      testing after outcome assessments. Participants will be balanced across self
      reported Hispanic versus non-Hispanic ethnicity (n=750 in personalized genomic
      testing for melanoma risk arm; n=135 in control arm), and will be recruited from
      a general population cohort in Albuquerque, New Mexico, which is subject to year
      round sun exposure. Baseline surveys will be completed in-person with study staff
      and follow-up measures will be completed via telephone. RESULTS: Aim 1 of the
      trial will examine the personal utility of personalized genomic testing for
      melanoma risk in terms of short-term (3-month) sun protection and skin screening
      behaviors, family and physician communication, and melanoma threat and control
      beliefs (ie, putative mediators of behavior change). We will also examine
      potential unintended consequences of testing among those who receive average-risk
      personalized genomic testing for melanoma risk findings, and examine predictors
      of sun protection at 3 months as the outcome. These findings will be used to
      develop messages for groups that receive average-risk feedback. Aim 2 will
      compare rates of test consideration in Hispanics versus non-Hispanics, including
      consideration of testing pros and cons and registration of a decision to either
      accept or decline testing. Aim 3 will examine personalized genomic testing for
      melanoma risk feedback comprehension, recall, satisfaction, and cancer-related
      distress in those who undergo testing, and whether these outcomes differ by
      ethnicity (Hispanic vs non-Hispanic), or sociocultural or demographic factors.
      Final outcome data collection is anticipated to be complete by October 2017, at
      which point data analysis will commence. CONCLUSIONS: This study has important
      implications for personalized genomics in the context of melanoma risk, and may
      be broadly applicable as a model for delivery of personalized genomic feedback
      for other health conditions.

PMID- 28442452
TI  - HomeStyles, A Web-Based Childhood Obesity Prevention Program for Families With
      Preschool Children: Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: The home environment is where young children spend most of their
      time, and is critically important to supporting behaviors that promote health and
      prevent obesity. However, the home environment and lifestyle patterns remain
      understudied, and few interventions have investigated parent-led makeovers
      designed to create home environments that are supportive of optimal child health
      and healthy child weights. OBJECTIVE: The aim of the HomeStyles randomized
      controlled trial (RCT) is to determine whether the Web-based HomeStyles
      intervention enables and motivates parents to shape the weight-related aspects of
      their home environments and lifestyle behavioral practices (diet, exercise, and
      sleep) to be more supportive of their preschool children's optimal health and
      weight. METHODS: A rigorous RCT utilizing an experimental group and an attention
      control group, receiving a bona fide contemporaneous treatment equal in
      nonspecific treatment effects and differing only in subject matter content, will
      test the effect of HomeStyles on a diverse sample of families with preschool
      children. This intervention is based on social cognitive theory and uses a social
      ecological framework, and will assess: intrapersonal characteristics (dietary
      intake, physical activity level, and sleep) of parents and children; family
      interpersonal or social characteristics related to diet, physical activity, media
      use, and parental values and self-efficacy for obesity-preventive practices; and
      home environment food availability, physical activity space and supports in and
      near the home, and media availability and controls in the home. RESULTS:
      Enrollment for this study has been completed and statistical data analyses are
      currently underway. CONCLUSIONS: This paper describes the HomeStyles intervention
      with regards to: rationale, the intervention's logic model, sample eligibility
      criteria and recruitment, experimental group and attention control intervention
      content, study design, instruments, data management, and planned analyses.

PMID- 28442453
TI  - Clickotine, A Personalized Smartphone App for Smoking Cessation: Initial
      Evaluation.
AB  - BACKGROUND: Tobacco smoking is the leading cause of preventable death in the
      United States, and the annual economic burden attributable to smoking exceeds US
      $300 billion. Obstacles to smoking cessation include limited access and adherence
      to effective cessation interventions. Technology can help overcome these
      obstacles; many smartphone apps have been developed to aid smoking cessation, but
      few that conform to the US clinical practice guideline (USCPG) have been
      rigorously tested and reported in the literature. Clickotine is a novel
      smartphone app for smoking cessation, designed to deliver the essential features
      of the USCPG and engineered to engage smokers by personalizing intervention
      components. OBJECTIVE: Our objective was to assess the engagement, efficacy, and
      safety of Clickotine in an initial, single-arm study. Outcomes measured were
      indicators of engagement with the smartphone app (number of app opens, number of
      interactions with the Clickotine program, and weeks active with Clickotine),
      cessation outcomes of 7- and 30-day self-reported abstinence from smoking, and
      negative health events. METHODS: We recruited US residents between 18 and 65
      years of age who owned an iPhone and smoked 5 or more cigarettes daily for the
      study via online advertising. Respondents were prescreened for eligibility by
      telephone and, if appropriate, directed to a Web portal to provide informed
      consent, confirm eligibility, and download the Clickotine app. Participants
      completed study assessments via the online portal at baseline and after 8 weeks.
      Data were collected in Amazon S3 with no manual data entry, and access to all
      data was maximally restrictive, logged, and auditable. RESULTS: A total of 416
      participants downloaded the app and constituted the intention-to-treat (ITT)
      sample. On average, participants opened the Clickotine app 100.6 times during the
      8-week study (median 69), logged 214.4 interactions with the Clickotine program
      (median 178), and remained engaged with Clickotine for 5.3 weeks (median 5).
      Among the ITT sample, 45.2% (188/416) reported 7-day abstinence and 26.2%
      (109/416) reported 30-day abstinence from smoking after 8 weeks. Completer
      analysis focused on 365 (87.7%) of the 416 enrolled participants who completed
      the 8-week questionnaire revealed that 51.5% (188/365) of completers reported 7
      day abstinence and 29.9% (109/365) reported 30-day abstinence. Few adverse
      events, mostly consistent with nicotine withdrawal symptoms, were reported and
      overall no safety signal was detected. CONCLUSIONS: In this initial single-arm
      trial, Clickotine users appeared to demonstrate encouraging indicators of
      engagement in terms of the number of app opens, number of program interactions,
      and continued engagement over time. Clickotine users reported encouraging quit
      rates while reporting few adverse events. Future research is warranted to assess
      Clickotine's efficacy in a randomized controlled trial. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02656745; https://clinicaltrials.gov/ct2/show/NCT02656745
      (Archived by WebCite at http://www.webcitation.org/6peTT4x60).

PMID- 28442454
TI  - Impact of Information and Communication Technologies on Nursing Care: Results of
      an Overview of Systematic Reviews.
AB  - BACKGROUND: Information and communication technologies (ICTs) are becoming an
      impetus for quality health care delivery by nurses. The use of ICTs by nurses can
      impact their practice, modifying the ways in which they plan, provide, document,
      and review clinical care. OBJECTIVE: An overview of systematic reviews was
      conducted to develop a broad picture of the dimensions and indicators of nursing
      care that have the potential to be influenced by the use of ICTs. METHODS:
      Quantitative, mixed-method, and qualitative reviews that aimed to evaluate the
      influence of four eHealth domains (eg, management, computerized decision support
      systems [CDSSs], communication, and information systems) on nursing care were
      included. We used the nursing care performance framework (NCPF) as an extraction
      grid and analytical tool. This model illustrates how the interplay between
      nursing resources and the nursing services can produce changes in patient
      conditions. The primary outcomes included nurses' practice environment, nursing
      processes, professional satisfaction, and nursing-sensitive outcomes. The
      secondary outcomes included satisfaction or dissatisfaction with ICTs according
      to nurses' and patients' perspectives. Reviews published in English, French, or
      Spanish from January 1, 1995 to January 15, 2015, were considered. RESULTS: A
      total of 5515 titles or abstracts were assessed for eligibility and full-text
      papers of 72 articles were retrieved for detailed evaluation. It was found that
      22 reviews published between 2002 and 2015 met the eligibility criteria. Many
      nursing care themes (ie, indicators) were influenced by the use of ICTs,
      including time management; time spent on patient care; documentation time;
      information quality and access; quality of documentation; knowledge updating and
      utilization; nurse autonomy; intra and interprofessional collaboration; nurses'
      competencies and skills; nurse-patient relationship; assessment, care planning,
      and evaluation; teaching of patients and families; communication and care
      coordination; perspectives of the quality of care provided; nurses and patients
      satisfaction or dissatisfaction with ICTs; patient comfort and quality of life
      related to care; empowerment; and functional status. CONCLUSIONS: The findings
      led to the identification of 19 indicators related to nursing care that are
      impacted by the use of ICTs. To the best of our knowledge, this was the first
      attempt to apply NCPF in the ICTs' context. This broad representation could be
      kept in mind when it will be the time to plan and to implement emerging ICTs in
      health care settings. TRIAL REGISTRATION: PROSPERO International Prospective
      Register of Systematic Reviews: CRD42014014762;
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014014762 (Archived
      by WebCite at http://www.webcitation.org/6pIhMLBZh).

PMID- 28442456
TI  - The Malaria System MicroApp: A New, Mobile Device-Based Tool for Malaria
      Diagnosis.
AB  - BACKGROUND: Malaria is a public health problem that affects remote areas
      worldwide. Climate change has contributed to the problem by allowing for the
      survival of Anopheles in previously uninhabited areas. As such, several groups
      have made developing news systems for the automated diagnosis of malaria a
      priority. OBJECTIVE: The objective of this study was to develop a new, automated,
      mobile device-based diagnostic system for malaria. The system uses Giemsa-stained
      peripheral blood samples combined with light microscopy to identify the
      Plasmodium falciparum species in the ring stage of development. METHODS: The
      system uses image processing and artificial intelligence techniques as well as a
      known face detection algorithm to identify Plasmodium parasites. The algorithm is
      based on integral image and haar-like features concepts, and makes use of weak
      classifiers with adaptive boosting learning. The search scope of the learning
      algorithm is reduced in the preprocessing step by removing the background around
      blood cells. RESULTS: As a proof of concept experiment, the tool was used on 555
      malaria-positive and 777 malaria-negative previously-made slides. The accuracy of
      the system was, on average, 91%, meaning that for every 100 parasite-infected
      samples, 91 were identified correctly. CONCLUSIONS: Accessibility barriers of low
      resource countries can be addressed with low-cost diagnostic tools. Our system,
      developed for mobile devices (mobile phones and tablets), addresses this by
      enabling access to health centers in remote communities, and importantly, not
      depending on extensive malaria expertise or expensive diagnostic detection
      equipment.

PMID- 28442455
TI  - Use of Fitness and Nutrition Apps: Associations With Body Mass Index, Snacking,
      and Drinking Habits in Adolescents.
AB  - BACKGROUND: Efforts to improve snacking and drinking habits are needed to promote
      a healthy body mass index (BMI) in adolescents. Although commercial fitness and
      nutrition mobile phone apps are widely used, little is known regarding their
      potential to improve health behaviors, especially in adolescents. In addition,
      evidence on the mechanisms through which such fitness and nutrition apps
      influence behavior is lacking. OBJECTIVES: This study assessed whether the use of
      commercial fitness or nutrition apps was associated with a lower BMI and
      healthier snacking and drinking habits in adolescents. Additionally, it explored
      if perceived behavioral control to eat healthy; attitudes to eat healthy for the
      good taste of healthy foods, for overall health or for appearance; social norm on
      healthy eating and social support to eat healthy mediated the associations
      between the frequency of use of fitness or nutrition apps and BMI, the healthy
      snack, and beverage ratio. METHODS: Cross-sectional self-reported data on snack
      and beverage consumption, healthy eating determinants, and fitness and nutrition
      app use of adolescents (N=889; mean age 14.7 years, SD 0.8; 54.8% [481/878] boys;
      18.1% [145/803] overweight) were collected in a representative sample of 20
      schools in Flanders, Belgium. Height and weight were measured by the researchers.
      The healthy snack ratio and the healthy beverage ratio were calculated as
      follows: gram healthy snacks or beverages/(gram healthy snacks or beverages+gram
      unhealthy snacks or beverages)*100. Multilevel regression and structural equation
      modeling were used to analyze the proposed associations and to explore multiple
      mediation. RESULTS: A total of 27.6% (245/889) of the adolescents used fitness,
      nutrition apps or both. Frequency of using nutrition apps was positively
      associated with a higher healthy beverage ratio (b=2.96 [1.11], P=.008) and a
      higher body mass index z-scores (zBMI; b=0.13 [0.05], P=.008. A significant
      interaction was found between the frequency of using nutrition and for the zBMI
      (b=-0.03 [0.02], P=.04) and the healthy snack ratio (b=-0.84 [0.37], P=.03).
      Attitude to eat healthy for appearance mediated both the fitness app use
      frequency-zBMI (a * b=0.02 [0.01], P=.02) and the nutrition app use frequency
      zBMI (a * b=0.04 [0.01], P=.001) associations. No mediation was observed for the
      associations between the frequency of use of fitness or nutrition apps and the
      healthy snack or beverage ratio. CONCLUSIONS: Commercial fitness and nutrition
      apps show some association with healthier eating behaviors and BMI in
      adolescents. However, effective behavior change techniques should be included to
      affect key determinants of healthy eating.

PMID- 28442457
TI  - A pseudotumour of the thigh: tensor fasciae latae muscle hypertrophy due to an
      underlying abductor tendon tear.
AB  - We present a patient with an asymptomatic unilateral swelling of the
      anterolateral thigh. MRI showed hypertrophy of the tensor fasciae latae muscle
      due to an underlying gluteus minimus tendon tear.Abductor tendon tears can
      present with swelling of the thigh due to secondary tensor fasciae latae muscle
      hypertrophy.

PMID- 28442459
TI  - US drug regulators should consider adding adults to SSRI suicide warning, says
      campaigner.

PMID- 28442460
TI  - Workload pressure would not be a defence against clinical negligence, barrister
      warns.

PMID- 28442458
TI  - Circulating MicroRNAs in Delayed Cerebral Infarction After Aneurysmal
      Subarachnoid Hemorrhage.
AB  - BACKGROUND: Delayed cerebral infarction (DCI) is a major cause of morbidities
      after aneurysmal subarachnoid hemorrhage (SAH) and typically starts at day 4 to 7
      after initial hemorrhage. MicroRNAs (miRNAs) play an important role in
      posttranscriptional gene expression control, and distinctive patterns of
      circulating miRNA changes have been identified for some diseases. We aimed to
      investigate miRNAs that characterize SAH patients with DCI compared with those
      without DCI. METHODS AND RESULTS: Circulating miRNAs were collected on day 7
      after SAH in healthy, SAH-free controls (n=20), SAH patients with DCI (n=20), and
      SAH patients without DCI (n=20). We used the LASSO (least absolute shrinkage and
      selection operator) method of regression analysis to characterize miRNAs
      associated with SAH patients with DCI compared with those without DCI. In the 28
      dysregulated miRNAs associated with DCI and SAH, we found that a combination of 4
      miRNAs (miR-4532, miR-4463, miR-1290, and miR-4793) could differentiate SAH
      patients with DCI from those without DCI with an area under the curve of 100%
      (95% CI 1.000-1.000, P<0.001). This 4-miRNA combination could also distinguish
      SAH patients with or without DCI from healthy controls with areas under the curve
      of 99.3% (95% CI 0.977-1.000, P<0.001) and 82.0% (95% CI 0.685-0.955, P<0.001),
      respectively. CONCLUSIONS: We found a 4-miRNA combination that characterized SAH
      patients with DCI. The findings could guide future mechanistic study to develop
      therapeutic targets.

PMID- 28442461
TI  - US doctors are charged with female genital mutilation for first time.

PMID- 28442462
TI  - Patients' and physiotherapists' belief in and use of acupuncture for cancer
      related symptoms.
AB  - BACKGROUND: It is important to investigate attitudes to acupuncture, because
      therapists' and patients' expectations may affect the treatment outcome. AIM: To
      explore the use of and belief in acupuncture among oncological physiotherapists
      and to explore patients' interest in receiving acupuncture during cancer therapy
      and their belief in its effectiveness. METHODS: 522 patients (80% female, mean
      age 67 years) reported on their interest in receiving acupuncture for nausea
      during radiotherapy treatment; a subgroup (n=198) additionally disclosed their
      belief in the effectiveness of acupuncture. 117 Swedish oncological
      physiotherapists (96% female, mean age 48 years) answered a questionnaire
      regarding their use of and belief in acupuncture. RESULTS: Of the patients
      initiating cancer therapy, 359 (69%) were interested in receiving acupuncture.
      The patients believed acupuncture to be effective for pain (79%), nausea (79%)
      and vasomotor symptoms (48%). Of the 117 physiotherapists, 66 (56%) practised
      acupuncture. Physiotherapists generally believed in the effectiveness of
      acupuncture. For pain, 89% believed that acupuncture was effective and 42% of
      them practised it. Similar responses were noted for chemotherapy-induced nausea
      (86% and 38%, respectively) and vasomotor symptoms (80% and 28%, respectively).
      Younger physiotherapists and patients were more likely to believe in the
      effectiveness of acupuncture compared with older ones. CONCLUSIONS: More than two
      thirds of patients with cancer were interested in receiving acupuncture during
      therapy. Patients and oncological physiotherapists believed that acupuncture was
      effective for cancer pain, nausea and vasomotor symptoms. Further studies of
      acupuncture for cancer-related symptoms and of the effect of patients' and
      clinicians' therapeutic relationships, including treatment expectations, would be
      welcome.

PMID- 28442463
TI  - HIV services are at risk from fragmentation, report warns.

PMID- 28442465
TI  - The Romanian adoption 'Experiment'.

PMID- 28442466
TI  - Preventing rotavirus in Africa.

PMID- 28442467
TI  - Recognition and assessment of atypical and ambiguous genitalia in the newborn.
AB  - The baby with atypical or ambiguous genitalia is usually born in secondary care.
      For most clinicians, this is an unfamiliar and challenging scenario with the
      potential for life-long ramifications arising from a consultation led by an
      unprepared clinician. Language needs to be used carefully with particular clarity
      when liaising with parents, local health professionals and the specialist
      multidisciplinary team. Confidence in the recognition and assessment of atypical
      or ambiguous genitalia in a newborn will guide the local clinician when deciding
      on the initial investigations required and is a foundation for subsequent
      management. The local team have key roles in the initial support for parents as
      well as managing expectations at a time of great uncertainty. There are numerous
      different diagnoses that can result in atypical or ambiguous genitalia. The
      clinical findings should guide the initial investigations, and there are many
      pitfalls when it comes to interpreting the results. The aim of this article is to
      provide an initial approach to the management of a baby born with atypical or
      ambiguous genitalia.

PMID- 28442468
TI  - Strengthening the global paediatric workforce: the need for a global strategy to
      ensure better health outcomes for children.

PMID- 28442469
TI  - Recurrent superficial lymphangitis after insect bites.

PMID- 28442470
TI  - Late outcomes in children with Langerhans cell histiocytosis.
AB  - INTRODUCTION: Langerhans cell histiocytosis (LCH) is a rare disease with diverse
      clinical courses. Despite improvement in survival outcomes in the recent decades,
      sequelae of the disease remain a concern. This study aimed to provide information
      on the long-term outcomes in patients with LCH, particularly on the sequelae and
      any associated factors. METHOD: Medical records of patients with diagnosis of LCH
      and being managed in our centre were retrospectively reviewed. Data on the
      courses of illness, mortality, intervention, types and time of late events were
      collected and analysed. RESULTS: 70 patients were included with a mean
      observation time of 12 years (median 10.7 years, range 1-31.3 years). Sequelae
      related to LCH were present in 56% (n=39), being more common in multisystem
      diseases and patients with reactivations. Prevalence of sequelae is as follows:
      orthopaedic related 27%, diabetes insipidus 19%, growth retardation 13%, cosmetic
      10%, neurological 7%, hearing 7%, anterior pituitary hormone deficiency 7%,
      hepatobiliary 4% and ophthalmological 3%. Neurological sequelae could manifest
      even 10 years after initial diagnosis of LCH. Reactivations, presence of central
      nervous system (CNS) risk lesions and treatment with radiotherapy were associated
      with a higher rate of sequelae. The cumulative incidence of reactivation was 34%.
      Most reactivations occurred in the first 2.5 years after diagnosis. CONCLUSION:
      Sequelae were common after LCH, although some were mild. Neurological sequelae
      could be particularly severe and debilitating. Vigilant long-term follow-up would
      be essential for optimising patient outcomes. Further studies on the prevention
      and treatment of CNS disease of LCH are warranted.

PMID- 28442471
TI  - Development of organoids from mouse and human endometrium showing endometrial
      epithelium physiology and long-term expandability.
AB  - The endometrium, which is of crucial importance for reproduction, undergoes
      dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular
      regulation is poor, primarily owing to a lack of study models. Here, we have
      established a novel and promising organoid model from both mouse and human
      endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT
      activating conditions, swiftly formed organoid structures that showed long-term
      expansion capacity, and reproduced the molecular and histological phenotype of
      the tissue's epithelium. The supplemented WNT level determined the type of mouse
      endometrial organoids obtained: high WNT yielded cystic organoids displaying a
      more differentiated phenotype than the dense organoids obtained in low WNT. The
      organoids phenocopied physiological responses of endometrial epithelium to
      hormones, including increased cell proliferation under estrogen and maturation
      upon progesterone. Moreover, the human endometrial organoids replicated the
      menstrual cycle under hormonal treatment at both the morpho-histological and
      molecular levels. Together, we established an organoid culture system for
      endometrium, reproducing tissue epithelium physiology and allowing long-term
      expansion. This novel model provides a powerful tool for studying mechanisms
      underlying the biology as well as the pathology of this key reproductive organ.

PMID- 28442473
TI  - David Oliver: From acute ward to care home-a journey fewer should take?

PMID- 28442474
TI  - Saturated fat does not clog the arteries: coronary heart disease is a chronic
      inflammatory condition, the risk of which can be effectively reduced from healthy
      lifestyle interventions.

PMID- 28442472
TI  - Functional and Metabolomic Consequences of KATP Channel Inactivation in Human
      Islets.
AB  - Loss-of-function mutations of beta-cell KATP channels cause the most severe form
      of congenital hyperinsulinism (KATPHI). KATPHI is characterized by fasting and
      protein-induced hypoglycemia that is unresponsive to medical therapy. For a
      better understanding of the pathophysiology of KATPHI, we examined cytosolic
      calcium ([Ca2+] i ), insulin secretion, oxygen consumption, and [U-13C]glucose
      metabolism in islets isolated from the pancreases of children with KATPHI who
      required pancreatectomy. Basal [Ca2+] i and insulin secretion were higher in
      KATPHI islets compared with controls. Unlike controls, insulin secretion in
      KATPHI islets increased in response to amino acids but not to glucose. KATPHI
      islets have an increased basal rate of oxygen consumption and mitochondrial mass.
      [U-13C]glucose metabolism showed a twofold increase in alanine levels and sixfold
      increase in 13C enrichment of alanine in KATPHI islets, suggesting increased
      rates of glycolysis. KATPHI islets also exhibited increased serine/glycine and
      glutamine biosynthesis. In contrast, KATPHI islets had low gamma-aminobutyric
      acid (GABA) levels and lacked 13C incorporation into GABA in response to glucose
      stimulation. The expression of key genes involved in these metabolic pathways was
      significantly different in KATPHI beta-cells compared with control, providing a
      mechanism for the observed changes. These findings demonstrate that the
      pathophysiology of KATPHI is complex, and they provide a framework for the
      identification of new potential therapeutic targets for this devastating
      condition.

PMID- 28442475
TI  - Fool's gold and chasing unicorns: USMLE Step 1 has no clothes!

PMID- 28442476
TI  - In the valley of the blind, the USMLE is king.

PMID- 28442477
TI  - Nobel Laureate A. V. Hill and the refugee scholars, 1933-1945.
AB  - A. V. Hill shared the 1922 Nobel Prize in Physiology or Medicine for his
      investigation of the energetics of muscular contraction. His scientific work has
      been well chronicled over many years (Rall JA. Mechanism of Muscular Contraction,
      2014). There is the natural tendency to focus solely on an investigator's
      scientific achievements. But in the case of Hill, it has been said (Katz B. Biogr
      Mem Fellows R Soc 24: 71-149, 1978) that "it was his devotion to such wider
      issues, outside the boundaries of his own research, through which he exerted his
      most important influence on other people's lives and on the course of events." It
      is A. V. Hill, the man, and his defense of science and of scientists driven from
      their places of work, which began with the Nazi rise to power in Germany in 1933,
      that will be explored.

PMID- 28442478
TI  - Validating a conceptual framework for the core concept of "cell-cell
      communication".
AB  - We have created and validated a conceptual framework for the core physiology
      concept of "cell-cell communication." The conceptual framework is composed of 51
      items arranged in a hierarchy that is, in some instances, four levels deep. We
      have validated it with input from faculty who teach at a wide variety of
      institutional types. All items making up the framework were deemed essential to
      moderately important. However, some of the main ideas were clearly judged to be
      more important than others. Furthermore, the lower in the hierarchy an item is,
      the less important it is thought to be. Finally, there was no significant
      difference in the ratings given by faculty at different types of institutions.

PMID- 28442479
TI  - Novel use of a noninvasive hemodynamic monitor in a personalized, active learning
      simulation.
AB  - The present study furthered the concept of simulation-based medical education by
      applying a personalized active learning component. We tested this novel approach
      utilizing a noninvasive hemodynamic monitor with the capability to measure and
      display in real time numerous hemodynamic parameters in the exercising
      participant. Changes in medical knowledge concerning physiology were examined
      with a pre-and posttest. Simply by observation of one's own hemodynamic
      variables, the understanding of complex physiological concepts was significantly
      enhanced.

PMID- 28442480
TI  - Structure-function relations in physiology education: Where's the mechanism?
AB  - Physiology demands systems thinking: reasoning within and between levels of
      biological organization and across different organ systems. Many physiological
      mechanisms explain how structures and their properties interact at one level of
      organization to produce emergent functions at a higher level of organization.
      Current physiology principles, such as structure-function relations, selectively
      neglect mechanisms by not mentioning this term explicitly. We explored how
      students characterized mechanisms and functions to shed light on how students
      make sense of these terms. Students characterized mechanisms as 1) processes that
      occur at levels of organization lower than that of functions; and 2) as detailed
      events with many steps involved. We also found that students produced more
      variability in how they characterized functions compared with mechanisms:
      students characterized functions in relation to multiple levels of organization
      and multiple definitions. We interpret these results as evidence that students
      see mechanisms as holding a more narrow definition than used in the biological
      sciences, and that students struggle to coordinate and distinguish mechanisms
      from functions due to cognitive processes germane to learning in many domains. We
      offer the instructional suggestion that we scaffold student learning by affording
      students opportunities to relate and also distinguish between these terms so
      central to understanding physiology.

PMID- 28442481
TI  - Avoiding the chopping block in curricular reform: reimagining physiology
      laboratories in the era of integrated medical curricula.

PMID- 28442483
TI  - Authors' reply to Mjoen and Holdaas.

PMID- 28442485
TI  - Citizens' assembly recommends unrestricted access to abortion in Ireland.

PMID- 28442482
TI  - BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines
      Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.
AB  - BACKGROUND: Critical limb ischemia is a manifestation of peripheral artery
      disease that carries significant mortality and morbidity risk in humans, although
      its genetic determinants remain largely unknown. We previously discovered 2
      overlapping quantitative trait loci in mice, Lsq-1 and Civq-1, that affected limb
      muscle survival and stroke volume after femoral artery or middle cerebral artery
      ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates
      with tissue protection from hind-limb ischemia. METHODS: We treated mice with
      either adeno-associated viruses encoding a control (green fluorescent protein) or
      2 BAG3 (Bcl-2-associated athanogene-3) variants, namely Met81 or Ile81, and
      subjected the mice to hind-limb ischemia. RESULTS: We found that the BAG3
      Ile81Met variant in the C57BL/6 (BL6) mouse background segregates with protection
      from tissue necrosis in a shorter congenic fragment of Lsq-1 (C.B6-Lsq1-3).
      BALB/c mice treated with adeno-associated virus encoding the BL6 BAG3 variant
      (Ile81; n=25) displayed reduced limb-tissue necrosis and increased limb tissue
      perfusion compared with Met81- (n=25) or green fluorescent protein- (n=29)
      expressing animals. BAG3Ile81, but not BAG3Met81, improved ischemic muscle
      myopathy and muscle precursor cell differentiation and improved muscle
      regeneration in a separate, toxin-induced model of injury. Systemic injection of
      adeno-associated virus-BAG3Ile81 (n=9), but not BAG3Met81 (n=10) or green
      fluorescent protein (n=5), improved ischemic limb blood flow and limb muscle
      histology and restored muscle function (force production). Compared with
      BAG3Met81, BAG3Ile81 displayed improved binding to the small heat shock protein
      (HspB8) in ischemic skeletal muscle cells and enhanced ischemic muscle autophagic
      flux. CONCLUSIONS: Taken together, our data demonstrate that genetic variation in
      BAG3 plays an important role in the prevention of ischemic tissue necrosis. These
      results highlight a pathway that preserves tissue survival and muscle function in
      the setting of ischemia.

PMID- 28442484
TI  - Low-dose leptin infusion in the fourth ventricle of rats enhances the response to
      third-ventricle leptin injection.
AB  - We previously reported that low-dose leptin infusions into the third or fourth
      ventricle that do not affect energy balance when given independently cause rapid
      weight loss when given simultaneously. Therefore, we tested whether hindbrain
      leptin enhances the response to forebrain leptin or whether forebrain leptin
      enhances the response to hindbrain leptin. Rats received fourth-ventricle
      infusions of saline or 0.01, 0.1, 0.3, or 0.6 MUg leptin/day for 13 days. On days
      9 and 13, 0.1 MUg leptin was injected into the third ventricle. The injection
      inhibited food intake for 36 h in saline-infused rats but for 60 h in those
      infused with 0.6 MUg leptin/day. Leptin injection increased intrascapular brown
      fat temperature in leptin-infused, but not saline-infused, rats. In a separate
      experiment, rats received third-ventricle infusions of saline or 0.005, 0.01,
      0.05, or 0.1 MUg leptin/day and fourth-ventricle injections of 1.0 MUg leptin on
      days 9 and 13 Leptin injection inhibited food intake, respiratory exchange ratio,
      and 14-h food intake in rats infused with saline or the two lowest doses of
      leptin. There was no effect with higher-dose leptin infusions because food
      intake, body fat, and lean mass were already inhibited. These data suggest that
      activation of leptin receptors in the hindbrain enhances the response to third
      ventricle leptin, whereas activation of forebrain leptin receptors does not
      enhance the response to fourth-ventricle leptin, consistent with our previous
      finding that weight loss in rats treated with fourth-ventricle leptin is
      associated with indirect activation of hypothalamic STAT3.

PMID- 28442486
TI  - Sepsis quality standards are laudable but have low specificity.

PMID- 28442487
TI  - Delays in GP rescue package are "unacceptable," says BMA.

PMID- 28442488
TI  - Paroxysms.

PMID- 28442489
TI  - Integrative genomics of gene and metabolic regulation by estrogen receptors alpha
      and beta, and their coregulators.

PMID- 28442490
TI  - NHS managers should face the same regulation as doctors, says Francis.

PMID- 28442492
TI  - Endothelin-A Receptor Antagonism Retards the Progression of Murine Sickle Cell
      Nephropathy.

PMID- 28442491
TI  - Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling
      Distal Tubules.
AB  - Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic
      hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view
      that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter
      (NCC) in the distal convoluted tubule (DCT) is solely responsible. However,
      aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and
      inhibition of the potassium-excretory renal outer medullary potassium (ROMK)
      channel have also been implicated. To test these ideas, we introduced kinase
      activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the
      terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich
      kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was
      specifically targeted to the early DCT using a DCT-driven Cre recombinase. CA
      SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent
      with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and
      consequent restoration of sodium excretion did not immediately restore urinary
      potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN
      remodeling, involving a reduction in connecting tubule mass and attenuation of
      epithelial sodium channel (ENaC) and ROMK expression and apical localization.
      Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC
      and ROMK expression, concurrent with the restoration of urinary potassium
      excretion. These findings verify that NCC hyperactivity underlies FHHt but also
      reveal that NCC-dependent changes in the driving force for potassium secretion
      are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process
      controls potassium balance in health and becomes aberrantly activated in FHHt.

PMID- 28442493
TI  - Characteristics and outcomes of Canadian MD/PhD program graduates: a cross
      sectional survey.
AB  - BACKGROUND: Combined MD/PhD programs provide a structured path for physician
      scientist training, but assessment of their success within Canada is limited by a
      lack of quantitative data. We collected outcomes data for graduates of Canadian
      MD/PhD programs. METHODS: We developed and implemented a Web-based survey
      consisting of 41 questions designed to collect outcomes data for Canadian MD/PhD
      program alumni from 8 Canadian universities who had graduated before September
      2015. Respondents were categorized into 2 groups according to whether they had or
      had not completed all training. RESULTS: Of the 186 eligible alumni of MD/PhD
      programs, 139 (74.7%) completed the survey. A total of 136/138 respondents
      (98.6%) had completed or were currently completing residency training, and 66/80
      (82%) had completed at least 1 postgraduate fellowship. Most (58 [83%]) of the 70
      respondents who had completed all training were appointed as faculty at academic
      institutions, and 37 (53%) had been principal investigators on at least 1 recent
      funded project. Among the 58 respondents appointed at academic institutions,
      44/57 (77%) dedicated at least 20% of their time to research, and 25/57 (44%)
      dedicated at least 50% to research. During their combined degree, 102/136
      respondents (75.0%) published 3 or more first-author papers, and 133/136 (97.8%)
      matched with their first choice of specialty. The median length of physician
      scientist training was 13.5 years. Most respondents graduated with debt despite
      having been supported by Canadian Institutes of Health Research MD/PhD
      studentships. INTERPRETATION: Most Canadian MD/PhD program alumni pursued careers
      consistent with their physician-scientist training, which indicates that these
      programs are meeting their primary objective. Nevertheless, our findings
      highlight that a minority of these positions are research intensive; this finding
      warrants further study. Our data provide a baseline for future monitoring of the
      output of Canadian MD/PhD programs.

PMID- 28442496
TI  - Gastro-oesophageal reflux events: just another trigger in chronic cough?

PMID- 28442495
TI  - Aspirin prevents NF-kappaB activation and CDX2 expression stimulated by acid and
      bile salts in oesophageal squamous cells of patients with Barrett's oesophagus.
AB  - OBJECTIVE: In previous studies using oesophageal squamous cells from patients
      with Barrett's oesophagus (normal oesophageal squamous (NES)-B cells) and from
      patients without Barrett's oesophagus (NES-G cells), we showed that acid and bile
      salts induced caudal-related homeobox transcription factor 2 (CDX2) expression
      only in NES-B cells. CDX2, a transcription factor required to form intestinal
      epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated
      B cells (NF-kappaB) signalling, which can be inhibited by aspirin. We explored
      mechanisms underlying differences between NES-B and NES-G cells in CDX2
      expression and effects of aspirin on that CDX2 expression. DESIGN: We exposed NES
      B and NES-G cells to acid and bile salts, with and without aspirin, and evaluated
      effects on IkappaB-NF-kappaB-PKAc complex activation, p65 NF-kappaB subunit
      function, and CDX2 expression. RESULTS: In both NES-B and NES-G cells, acid and
      bile salts activated nicotinamide adenine dinucleotide phosphate oxidase to
      generate H2O2, which activated the IkappaB-NF-kappaB-PKAc complex. NES-B cells
      exhibited higher levels of phosphorylated IkappaB and p65 and greater NF-kappaB
      transcriptional activity than NES-G cells, indicating greater IkappaB-NF-kappaB
      PKAc complex activation by acid and bile salts in NES-B cells, and p65 siRNA
      prevented their increased expression of CDX2. Aspirin blocked IkappaB
      phosphorylation, p65 nuclear translocation, CDX2 promoter activation and CDX2
      expression induced by acid and bile salts in NES-B cells. CONCLUSIONS:
      Differences between NES-B and NES-G cells in NF-kappaB activation by acid and
      bile salts can account for their differences in CDX2 expression, and their CDX2
      expression can be blocked by aspirin. These findings might explain why some
      patients with GORD develop Barrett's oesophagus while others do not, and why
      aspirin might protect against development of Barrett's oesophagus.

PMID- 28442497
TI  - An in silico model of retinal cholesterol dynamics (RCD model): insights into the
      pathophysiology of dry AMD.
AB  - We developed an in silico mathematical model of retinal cholesterol (Ch) dynamics
      (RCD) to quantify the physiological rate of Ch turnover in the rod outer segment
      (ROS), the lipoprotein transport mechanisms by which Ch enters and leaves the
      outer retina, and the rates of drusen growth and macrophage-mediated clearance in
      dry age-related macular degeneration. Based on existing experimental data and
      mechanistic hypotheses, we estimated the Ch turnover rate in the ROS to be 1-6
      pg/mm2/min, dependent on the rate of Ch recycling in the outer retina, and found
      comparable rates for LDL receptor-mediated endocytosis of Ch by the retinal
      pigment epithelium (RPE), ABCA1-mediated Ch transport from the RPE to the outer
      retina, ABCA1-mediated Ch efflux from the RPE to the choroid, and the secretion
      of 70 nm ApoB-Ch particles from the RPE. The drusen growth rate is predicted to
      increase from 0.7 to 4.2 MUm/year in proportion to the flux of ApoB-Ch particles.
      The rapid regression of drusen may be explained by macrophage-mediated clearance
      if the macrophage density reaches ~3,500 cells/mm2 The RCD model quantifies
      retinal Ch dynamics and suggests that retinal Ch turnover and recycling, ApoB-Ch
      particle efflux, and macrophage-mediated clearance may explain the dynamics of
      drusen growth and regression.

PMID- 28442498
TI  - Identification and characterization of a novel PPARalpha-regulated and 7alpha
      hydroxyl bile acid-preferring cytosolic sulfotransferase mL-STL (Sult2a8).
AB  - PPARalpha has been known to play a pivotal role in orchestrating lipid, glucose,
      and amino acid metabolism via transcriptional regulation of its target gene
      expression during energy deprivation. Recent evidence has also suggested that
      PPARalpha is involved in bile acid metabolism, but how PPARalpha modulates the
      homeostasis of bile acids during fasting is still not clear. In a mechanistic
      study aiming to dissect the spectrum of PPARalpha target genes involved in
      metabolic response to fasting, we identified a novel mouse gene (herein named mL
      STL for mouse liver-sulfotransferase-like) that shared extensive homology with
      the Sult2a subfamily of a superfamily of cytosolic sulfotransferases, implying
      its potential function in sulfonation. The mL-STL gene expressed predominantly in
      liver in fed state, but PPARalpha was required to sustain its expression during
      fasting, suggesting a critical role of PPARalpha in regulating the mL-STL
      mediated sulfonation during fasting. Functional studies using recombinant His
      tagged mL-STL protein revealed its narrow sulfonating activities toward 7alpha
      hydroxyl primary bile acids, including cholic acid, chenodeoxycholic acid, and
      alpha-muricholic acid, and thus suggesting that mL-STL may be the major hepatic
      bile acid sulfonating enzyme in mice. Together, these studies identified a novel
      PPARalpha-dependent gene and uncovered a new role of PPARalpha as being an
      essential regulator in bile acid biotransformation via sulfonation during
      fasting.

PMID- 28442499
TI  - Absorption, Distribution, Metabolism, and Excretion of the Oral Prostaglandin D2
      Receptor 2 Antagonist Fevipiprant (QAW039) in Healthy Volunteers and In Vitro.
AB  - Fevipiprant is a novel oral prostaglandin D2 receptor 2 (DP2; also known as
      CRTh2) antagonist, which is currently in development for the treatment of severe
      asthma and atopic dermatitis. We investigated the absorption, distribution,
      metabolism, and excretion properties of fevipiprant in healthy subjects after a
      single 200-mg oral dose of [14C]-radiolabeled fevipiprant. Fevipiprant and
      metabolites were analyzed by liquid chromatography coupled to tandem mass
      spectrometry and radioactivity measurements, and mechanistic in vitro studies
      were performed to investigate clearance pathways and covalent plasma protein
      binding. Biotransformation of fevipiprant involved predominantly an inactive acyl
      glucuronide (AG) metabolite, which was detected in plasma and excreta,
      representing 28% of excreted drug-related material. The AG metabolite was found
      to covalently bind to human plasma proteins, likely albumin; however, in vitro
      covalent binding to liver protein was negligible. Excretion was predominantly as
      unchanged fevipiprant in urine and feces, indicating clearance by renal and
      possibly biliary excretion. Fevipiprant was found to be a substrate of
      transporters organic anion transporter 3 (OAT3; renal uptake), multidrug
      resistance gene 1 (MDR1; possible biliary excretion), and organic anion
      transporting polypeptide 1B3 (OATP1B3; hepatic uptake). Elimination of
      fevipiprant occurs via glucuronidation by several uridine 5'-diphospho
      glucuronosyltransferase (UGT) enzymes as well as direct excretion. These parallel
      elimination pathways result in a low risk of major drug-drug interactions or
      pharmacogenetic/ethnic variability for this compound.

PMID- 28442500
TI  - High-Fat Diet Feeding Alters Expression of Hepatic Drug-Metabolizing Enzymes in
      Mice.
AB  - Medical conditions accompanying obesity often require drug therapy, but whether
      and how obesity alters the expression of drug-metabolizing enzymes and thus drug
      pharmacokinetics is poorly defined. Previous studies have shown that high-fat
      diet (HFD) feeding and subsequent obesity in mice lead to altered expression of
      transcriptional regulators for cytochrome P450 CYP2D6, including hepatocyte
      nuclear factor 4alpha (HNF4alpha, a transcriptional activator of CYP2D6) and
      small heterodimer partner (SHP, a transcriptional repressor of CYP2D6). The
      objective of this study was to examine whether diet-induced obesity alters CYP2D6
      expression by modulating HNF4alpha and SHP expression. Male CYP2D6-humanized
      transgenic (Tg-CYP2D6) mice were fed with HFD or matching control diet for 18
      weeks. Hepatic mRNA expression of CYP2D6 decreased to a small extent in the HFD
      group (by 31%), but the differences in CYP2D6 protein and activity levels in
      hepatic S9 fractions were found insignificant between the groups. Although
      hepatic SHP expression did not differ between the groups, HNF4alpha mRNA and
      protein levels decreased by ~30% in the HFD group. Among major mouse endogenous
      cytochrome P450 genes, Cyp1a2 and Cyp2c37 showed significant decreases in the HFD
      group, whereas Cyp2e1 expression did not differ between groups. Cyp2b10 and
      Cyp3a11 expression was higher in the HFD group, with corresponding 2.9-fold
      increases in hepatic CYP3A activities in HFD-fed mice. Together, these results
      suggest that obesity has minimal effects on CYP2D6-mediated drug metabolism,
      although it modulates the expression of mouse endogenous P450s in a gene-specific
      manner.

PMID- 28442501
TI  - ChloroKB: A Web Application for the Integration of Knowledge Related to
      Chloroplast Metabolic Network.
AB  - Higher plants, as autotrophic organisms, are effective sources of molecules. They
      hold great promise for metabolic engineering, but the behavior of plant
      metabolism at the network level is still incompletely described. Although
      structural models (stoichiometry matrices) and pathway databases are extremely
      useful, they cannot describe the complexity of the metabolic context, and new
      tools are required to visually represent integrated biocurated knowledge for use
      by both humans and computers. Here, we describe ChloroKB, a Web application
      (http://chlorokb.fr/) for visual exploration and analysis of the Arabidopsis
      (Arabidopsis thaliana) metabolic network in the chloroplast and related cellular
      pathways. The network was manually reconstructed through extensive biocuration to
      provide transparent traceability of experimental data. Proteins and metabolites
      were placed in their biological context (spatial distribution within cells,
      connectivity in the network, participation in supramolecular complexes, and
      regulatory interactions) using CellDesigner software. The network contains 1,147
      reviewed proteins (559 localized exclusively in plastids, 68 in at least one
      additional compartment, and 520 outside the plastid), 122 proteins awaiting
      biochemical/genetic characterization, and 228 proteins for which genes have not
      yet been identified. The visual presentation is intuitive and browsing is fluid,
      providing instant access to the graphical representation of integrated processes
      and to a wealth of refined qualitative and quantitative data. ChloroKB will be a
      significant support for structural and quantitative kinetic modeling, for
      biological reasoning, when comparing novel data with established knowledge, for
      computer analyses, and for educational purposes. ChloroKB will be enhanced by
      continuous updates following contributions from plant researchers.

PMID- 28442502
TI  - Ribonucleotide Reductase Catalytic Subunit M1 (RRM1) as a Novel Therapeutic
      Target in Multiple Myeloma.
AB  - Purpose: To investigate the biological and clinical significance of
      ribonucleotide reductase (RR) in multiple myeloma.Experimental Design: We
      assessed the impact of RR expression on patient outcome in multiple myeloma. We
      then characterized the effect of genetic and pharmacologic inhibition of
      ribonucleotide reductase catalytic subunit M1 (RRM1) on multiple myeloma growth
      and survival using siRNA and clofarabine, respectively, in both in vitro and in
      vivo mouse xenograft models.Results: Newly diagnosed multiple myeloma patients
      with higher RRM1 expression have shortened survival. Knockdown of RRM1 triggered
      significant growth inhibition and apoptosis in multiple myeloma cells, even in
      the context of the bone marrow microenvironment. Gene expression profiling showed
      upregulation of DNA damage response genes and p53-regulated genes after RRM1
      knockdown. Immunoblot and qRT-PCR analysis confirmed that gamma-H2A.X, ATM, ATR,
      Chk1, Chk2, RAD51, 53BP1, BRCA1, and BRCA2 were upregulated/activated. Moreover,
      immunoblots showed that p53, p21, Noxa, and Puma were activated in p53 wild-type
      multiple myeloma cells. Clofarabine, a purine nucleoside analogue that inhibits
      RRM1, induced growth arrest and apoptosis in p53 wild-type cell lines. Although
      clofarabine did not induce cell death in p53-mutant cells, it did trigger
      synergistic toxicity in combination with DNA-damaging agent melphalan. Finally,
      we demonstrated that tumor growth of RRM1-knockdown multiple myeloma cells was
      significantly reduced in a murine human multiple myeloma cell xenograft
      model.Conclusions: Our results therefore demonstrate that RRM1 is a novel
      therapeutic target in multiple myeloma in the preclinical setting and provide the
      basis for clinical evaluation of RRM1 inhibitor, alone or in combination with DNA
      damaging agents, to improve patient outcome in multiple myeloma. Clin Cancer Res;
      23(17); 5225-37. (c)2017 AACR.

PMID- 28442503
TI  - Molecular Pathways: Targeting the Protein Kinase Wee1 in Cancer.
AB  - Wee1 is a protein kinase that regulates the G2 checkpoint and prevents entry into
      mitosis in response to DNA damage. Cyclin-dependent kinases (CDK) are a family of
      14 serine/threonine protein kinases that coordinate the progression through the
      cell cycle. The Cdc2/cyclin B complex controls the progression from G2 into
      mitosis. There are two mechanisms by which the G2 checkpoint is initiated in
      response to DNA damage: phosphorylation of Cdc25c by CHK1 and of the Wee1 kinase,
      which phosphorylates Cdc2. Blockade at the G2 checkpoint is especially important
      for p53-mutant cells because these tumors mainly rely on DNA repair at the G2
      checkpoint. AZD1775 (formerly MK-1775) is a small-molecule, pyrazol-pyrimidine
      derivative and potent and ATP-competitive specific inhibitor of the Wee1 kinase.
      Several preclinical and clinical studies demonstrated encouraging antitumor
      effects with manageable side effects of the combination of Wee1 inhibition and
      DNA-damaging agents. Promising combination schedules are being investigated at
      the moment, for example, combining PARP inhibition and Wee1 inhibition. Also, a
      weekly schedule with carboplatin and AZD1775 warrants investigation aimed at
      further improving the antitumor effect. Clin Cancer Res; 23(16); 4540-4. (c)2017
      AACR.

PMID- 28442504
TI  - Characterization of the T-Cell Receptor Repertoire and Immune Microenvironment in
      Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and
      Neck.
AB  - Purpose: Squamous cell carcinoma of the head and neck (SCCHN) is a lethal cancer
      with a suboptimal 5-year overall survival of approximately 50% with surgery
      and/or definitive chemoradiotherapy. Novel treatments are thus urgently awaited.
      Immunotherapy with checkpoint blockade has emerged as a promising option for
      patients with recurrent/metastatic SCCHN; however, it has not been investigated
      in the curative-intent setting yet. The purpose of this study was to investigate
      the T-cell receptor repertoire and the tumor microenvironment in tumor tissues of
      SCCHN patients with locoregionally advanced disease.Experimental Design: We
      performed T-cell receptor sequencing of tumor tissues from 44 patients with
      locoregionally advanced SCCHN prior to treatment with definitive
      chemoradiotherapy and correlated the T-cell clonality and the mRNA expression
      levels of immune-related genes with clinicopathologic parameters.Results: Clonal
      expansion of T cells was significantly higher in human papilloma virus (HPV)
      negative compared with HPV-positive tumors, signifying more robust antigen
      presentation in HPV-negative tumors. The latter was supported by the higher
      percentage of HPV-negative tumors expressing HLA-A protein compared with HPV
      positive tumors (P = 0.049). Higher GRZB levels correlated significantly with
      longer recurrence-free survival (log-rank, P = 0.003) independent of tumor size,
      nodal stage, and HPV status.Conclusions: Our findings support clonal expansion of
      T cells in SCCHN patients with locoregionally advanced disease and imply
      differences in the antigen presentation capacity between HPV-negative and HPV
      positive tumors. Elevated GRZB mRNA levels may also serve as a favorable and
      independent predictor of outcome in SCCHN patients treated with
      chemoradiotherapy. These data provide rationale for the introduction of
      immunotherapeutic approaches in the curative-intent setting. Clin Cancer Res;
      23(16); 4897-907. (c)2017 AACR.

PMID- 28442505
TI  - Overexpressed Fatty Acid Synthase in Gastrointestinal Stromal Tumors: Targeting a
      Progression-Associated Metabolic Driver Enhances the Antitumor Effect of
      Imatinib.
AB  - Purpose: In gastrointestinal stromal tumors (GIST), lipid-metabolizing enzymes
      remain underexplored, including fatty acid synthase (FASN).Experimental Design:
      Forty GISTs were quantitated for FASN mRNA abundance. FASN immunoexpression was
      informative in 350 GISTs, including 213 with known KIT/PDGFRA/BRAF genotypes. In
      imatinib-resistant FASN-overexpressing GIST cells, the roles of overexpressed
      FASN and FASN-targeting C75 in tumor phenotypes, apoptosis and autophagy, KIT
      transcription, PI3K/AKT/mTOR activation, and imatinib resistance were analyzed by
      RNAi or myristoylated-AKT transfection. The therapeutic relevance of dual
      blockade of FASN and KIT was evaluated in vivoResults:FASN mRNA abundance
      significantly increased from very low/low-risk to high-risk levels of NCCN
      guidelines (P < 0.0001). FASN overexpression was associated with a nongastric
      location (P = 0.05), unfavorable genotype (P = 0.005), and increased risk level
      (P < 0.001) and independently predicted shorter disease-free survival (P <
      0.001). In vitro, FASN knockdown inhibited cell growth and migration, inactivated
      the PI3K/AKT/mTOR pathway, and resensitized resistant GIST cells to imatinib. C75
      transcriptionally repressed the KIT promoter, downregulated KIT expression and
      phosphorylation, induced LC3-II and myristoylated AKT-suppressible activity of
      caspases 3 and 7, attenuated the PI3K/AKT/mTOR/RPS6/4E-BP1 pathway activation,
      and exhibited dose-dependent therapeutic additivism with imatinib. Compared with
      both monotherapies, the C75/imatinib combination more effectively suppressed the
      growth of xenografts, exhibiting decreased KIT phosphorylation, Ki-67, and
      phosphorylated PI3K/AKT/mTOR levels and increased TUNEL labeling.Conclusions: We
      have characterized the prognostic, biological, and therapeutic implications of
      overexpressed FASN in GISTs. C75 represses KIT transactivation, abrogates
      PI3K/AKT/mTOR activation, and provides a rationale for dual blockade of KIT and
      FASN in treating imatinib-resistant GISTs. Clin Cancer Res; 23(16); 4908-18.
      (c)2017 AACR.

PMID- 28442506
TI  - Genome-Wide Association Studies of Chemotherapeutic Toxicities: Genomics of
      Inequality.
AB  - With an estimated global population of cancer survivors exceeding 32 million and
      growing, there is a heightened awareness of the long-term toxicities resulting
      from cancer treatments and their impact on quality of life. Unexplained
      heterogeneity in the persistence and development of toxicities, as well as an
      incomplete understanding of their mechanisms, have generated a growing need for
      the identification of predictive pharmacogenomic markers. Early studies
      addressing this need used a candidate gene approach; however, over the last
      decade, unbiased and comprehensive genome-wide association studies (GWAS) have
      provided markers of phenotypic risk and potential targets to explore the
      mechanistic and regulatory pathways of biological functions associated with
      chemotherapeutic toxicity. In this review, we provide the current status of GWAS
      of chemotherapeutic toxicities with an emphasis on examining the ancestral
      diversity of the representative cohorts within these studies. Persistent calls to
      incorporate both ancestrally diverse and/or admixed populations into genomic
      efforts resulted in a recent rise in the number of studies utilizing cohorts of
      East Asian descent; however, few pharmacogenomic studies to date include cohorts
      of African, Indigenous American, Southwest Asian, and admixed populations.
      Through comprehensively evaluating sample size, composition by ancestry, genome
      wide significant variants, and population-specific minor allele frequencies as
      reported by HapMap/dbSNP using NCBI PubMed and the NHGRI-EBI GWAS Catalog, we
      illustrate how allele frequencies and effect sizes tend to vary among individuals
      of differing ancestries. In an era of personalized medicine, the lack of
      diversity in genome-wide studies of anticancer agent toxicity may contribute to
      the health disparity gap. Clin Cancer Res; 23(15); 4010-9. (c)2017 AACR.

PMID- 28442508
TI  - Aging human body: changes in bone, muscle and body fat with consequent changes in
      nutrient intake.
AB  - Aging affects almost all physiological processes, but changes in body composition
      and body phenotype are most observable. In this review, we focus on these
      changes, including loss of bone and muscle and increase in body fat or
      redistribution of the latter, possibly leading to osteosarcopenic obesity
      syndrome. We also address low-grade chronic inflammation, prevalent in aging
      adults and a cause of many disorders including those associated with body
      composition. Changes in dietary intake and nutritional requirements of older
      individuals, that all may lead to some disturbances on tissue and organ levels,
      are discussed as well. Finally, we discuss the hormonal changes in the aging
      body, considering each of the tissues, bone, muscle and fat as separate endocrine
      organs, but yet in the continuous interface and communication with each other.
      Although there are still many unanswered questions in this field, this review
      will enable the readers to better understand the aging human body and measures
      needing to be implemented toward reducing impaired health and disability in older
      individuals.

PMID- 28442507
TI  - Protein kinase STK25 aggravates the severity of non-alcoholic fatty pancreas
      disease in mice.
AB  - Characterising the molecular networks that negatively regulate pancreatic beta
      cell function is essential for understanding the underlying pathogenesis and
      developing new treatment strategies for type 2 diabetes. We recently identified
      serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat
      storage, meta-inflammation, and fibrosis in liver and skeletal muscle. Here, we
      assessed the role of STK25 in control of progression of non-alcoholic fatty
      pancreas disease in the context of chronic exposure to dietary lipids in mice. We
      found that overexpression of STK25 in high-fat-fed transgenic mice aggravated
      diet-induced lipid storage in the pancreas compared with that of wild-type
      controls, which was accompanied by exacerbated pancreatic inflammatory cell
      infiltration, stellate cell activation, fibrosis and apoptosis. Pancreas of Stk25
      transgenic mice also displayed a marked decrease in islet beta/alpha-cell ratio
      and alteration in the islet architecture with an increased presence of alpha
      cells within the islet core, whereas islet size remained similar between
      genotypes. After a continued challenge with a high-fat diet, lower levels of
      fasting plasma insulin and C-peptide, and higher levels of plasma leptin, were
      detected in Stk25 transgenic vs wild-type mice. Furthermore, the glucose
      stimulated insulin secretion was impaired in high-fat-fed Stk25 transgenic mice
      during glucose tolerance test, in spite of higher net change in blood glucose
      concentrations compared with wild-type controls, suggesting islet beta-cell
      dysfunction. In summary, this study unravels a role for STK25 in determining the
      susceptibility to diet-induced non-alcoholic fatty pancreas disease in mice in
      connection to obesity. Our findings highlight STK25 as a potential drug target
      for metabolic disease.

PMID- 28442509
TI  - Long term risk of mortality after living kidney donation.

PMID- 28442510
TI  - Shuntaro Hida.

PMID- 28442511
TI  - Circulating miRNA Profiles of Doxorubicin-induced Cardiotoxicity in Breast Cancer
      Patients.
AB  - Doxorubicin (DOX) cardiotoxicity is unpredictable and begins with the first dose
      of chemotherapy. This study aimed to obtain information about circulating
      microRNA of cancer patients in the early dose of DOX chemotherapy, who either did
      or did not develop cardiac abnormality after the completion of chemotherapy.
      Plasma of 20 patients treated for breast cancer with DOX-chemotherapy was
      analyzed using quantitative RT-PCR. Circulating microRNA profiles of patients
      with DOX cardiotoxicity were compared to microRNA profiles of patients without
      DOX cardiotoxicity by quantitative real-time PCR. Thirty-two microRNAs were
      significantly dysregulated in the patients with abnormal cardiac function.
      Functional analysis of the 32 miRNAs suggested association with cell death, cell
      cycle, and inflammation. We have identified a miRNA signature associated with
      early doses of DOX-based chemotherapy that may potentially predict later
      impairment of cardiac function in breast cancer patients. Our data lay a
      foundation for future studies to identify biomarkers for presymptomatic DOX
      induced cardiotoxicity.

PMID- 28442512
TI  - The Clinical Value of Hepcidin in Breast Cancer and Its Bone Metastasis.
AB  - PURPOSE: We explored the role of hepcidin in the progression of breast cancer.
      METHODS: A retrospective analysis of 25 breast cancer patients with bone
      metastases, 30 breast cancer patients without bone metastases, and 30 patients
      with breast hyperplasia was conducted to compare the differences in Hb, hepcidin,
      BMP6, IL-6, and sTfR among the three groups and explore the correlation of
      Hepcidin with BMP6 IL-6, Hb and sTfR. In addition, ROC analysis was performed to
      evaluate the diagnostic value of hepcidin, BMP6 and IL-6 in breast cancer and its
      bone metastasis, while multivariate Logistic regression analysis was conducted to
      compare various indicators in breast cancer and its bone metastasis. RESULTS: The
      incidence of anemia was significantly different among three groups; hepcidin,
      BMP6, IL-6, sTfR, and Hb were also significantly different. Hepcidin level has a
      significant correlation with IL-6 and Hb levels in breast cancer patients with
      bone metastasis. Hepcidin had a higher diagnostic value for both breast cancer
      and breast cancer with bone metastasis than both BMP6 and IL-6. Hepcidin was an
      independent risk factor for breast cancer and its bone metastasis. CONCLUSION:
      Hepcidin can very well be utilized as a potential prognostic marker to follow
      patients with breast cancer metastatic to bone.

PMID- 28442513
TI  - Histopathological Significance and Prognostic Impact of Tumor Budding in
      Colorectal Cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease with complex
      etiology. New prognostic factors for this group of disease need to be
      investigated. This study evaluated the histopathological significance and
      prognostic impact of tumor budding in CRC. DESIGN: A total of 60 treatment naive
      consecutive patients undergoing surgical resection for CRC during the period of
      January 2011 to December 2013 were included in the study. Details of each patient
      related to their demographic and tumor profile were recorded. Pan Cytokeratin
      immunohistochemistry was applied on chosen sections and tumor budding was
      assessed. RESULTS: The most frequent site of involvement was rectosigmoid and
      sigmoid colon (31.6%). The majority of the cases were moderately differentiated
      (75%) in morphology, and showed tumor invasion into the pericolic/subserosal fat
      (66.6%), and were stage III (38.3%). Nodal involvement was present in 50% cases.
      Correlations between tumor budding and nodal involvement (p-value 0.039) and AJCC
      stage (p-value 0.021) were found to be statistically significant. CONCLUSION:
      Tumor budding may be a promising and powerful predictor of lymphnodal metastasis
      and a higher stage of tumor and can be used as a marker for assessing the
      aggressiveness of CRC. Routine hemotoxylin-eosin staining supported by
      cytokeratin immunostain can aid in the grading of tumor budding in CRC.

PMID- 28442514
TI  - CD3 and CD20 Immunohistochemical Staining Patterns of Bone Marrow-Infiltrating
      Malignant Lymphoma Cells.
AB  - OBJECTIVES: It is known that CD3 and CD20 are homogenously expressed in T lineage
      and B lineage lymphoma, respectively; however, there are no standard guidelines
      to interpret immunohistochemistry findings. In this study, we investigated CD3
      and CD20 immunohistochemical staining patterns of bone marrow (BM)-infiltrating
      lymphoma cells. METHODS: Among 297 patients diagnosed with malignant lymphoma,
      the BM biopsy slides of all 39 cases found to have BM infiltration (T lineage:
      11; B lineage: 28) were reviewed. We specifically investigated the
      immunohistochemical staining patterns of CD3 and CD20. RESULTS: All 11 T lineage
      lymphoma cases showed homogenous immunohistochemical staining patterns. In the 28
      B lineage lymphoma cases, 15 (53.6%) showed a homogenous pattern while 13 (46.4%)
      showed a heterogeneous pattern. Ten cases in the latter group showed additional
      evidence of BM infiltration by lymphoma cells in separate laboratory analyses or
      imaging studies. There were no differences in overall or progression-free
      survival rates in patients exhibiting homogeneous vs. heterogeneous staining
      patterns (P=0.81 and P=0.59, respectively). CONCLUSIONS: A considerable number of
      B lineage cases showed heterogeneous patterns with evidence of BM infiltration.
      Thus, heterogeneous immunohistochemical staining patterns (particularly in B
      lineage lymphomas) may signify malignant lymphoma cell infiltration into the BM.

PMID- 28442515
TI  - Genetic Polymorphisms rs699947, rs1570360, and rs3025039 on the VEGF Gene Are
      Correlated with Extracranial Internal Carotid Artery Stenosis and Ischemic
      Stroke.
AB  - Extracranial internal carotid artery (ECICA) stenosis is a modifiable risk factor
      of ischemic stroke. VEGF plays a crucial role in the maintenance of endothelial
      integrity and physiological function. This study was designed to assess the
      correlations of VEGF polymorphisms with ECICA stenosis in ischemic stroke and to
      explore the relationships between these polymorphisms and different biochemical
      parameters. This study included a total of 650 ischemic stroke patients, 232 with
      ECICA stenosis while 418 had no ECICA stenosis as assessed by magnetic resonance
      angiography. Three SNPs in the VEGF gene, rs699947, rs1570360, and rs3025039,
      were assessed by real-time PCR coupled with melting curve analysis. Serum samples
      were analyzed for biochemical parameters in an automated clinical chemistry
      analyzer in the Laboratory Medicine Department. The CA and CA+AA (A allele
      bearing) genotype frequencies of the rs699947 polymorphism (AOR=1.46 and 1.47,
      respectively) and the GA genotype frequency of the rs1570360 polymorphism
      (AOR=7.33) showed a significant association with ECICA stenosis. However, the
      haplotype frequencies of C-A-A, T-A-C, and T-A-A (rs302503-rs1570360-rs699947)
      were significantly different between patients who experienced stroke with and
      stroke without ECICA stenosis. We found that the total homocysteine (tHcy) levels
      of stroke patients with ECICA stenosis with rs1570360 and rs699947 SNPs were
      significantly different compared to the wild-type reference genotype. In
      conclusion, VEGF rs699947 and rs3025039 polymorphisms were associated with
      increased risk of stroke, while rs1570360 and rs699947 were associated with
      stroke and ECICA stenosis.

PMID- 28442516
TI  - In vitro Study of the Thrombogenic Activity of Platelet-derived Microparticles
      from Patients with Acute Coronary Syndrome.
AB  - BACKGROUND: To observe the thrombogenic activity of platelet-derived
      microparticles (PMPs) in PMP-free plasma from non-coronary artery disease (non
      CAD) patients and explore the relationship between PMPs and thrombosis in acute
      coronary syndrome (ACS) patients. METHODS: Patients with ACS who were diagnosed
      at the outpatient department of cardiology in the People's Hospital of Xinjiang
      Uygur Autonomous Region, and non-CAD subjects were enrolled in the study from
      January 2011 to December 2014. Subjects were assigned to the ACS group (n=200)
      (which consisted of patients with acute myocardial infarction (AMI, n=100) and
      patients with unstable angina pectoris) (UAP, n=100), or to the non-CAD group
      (n=100). After informed consent was obtained from subjects, peripheral blood was
      collected from ACS patients and non-CAD subjects and then put into sodium citrate
      anticoagulant tubes. The PMPs were analyzed by flow cytometry using flow
      cytometry. The plasma of non-CAD patients was thawed and centrifuged to obtain MP
      free plasma. MP-free plasma was placed into a black 96-well microplate at 40 MUl
      per well. 10 MUl PMP suspension containing 1*103, 1*104 or 1*105 PMPs from ACS
      patients or non-CAD patients was added into the MP-free plasma. The coagulation
      reaction was induced by adding 50 MUl of fluorescence-labeled thrombin substrate,
      and the microplate was placed into the microplate reader. RESULTS: Compared with
      the PMP levels in the non-CAD patient group (40*103), the PMPs were increased in
      the AMI sub-group (250*103) and the UAP sub-group (126*103) of the ACS patients,
      and the differences were statistically significant (P<0.05). The relative
      fluorescence intensity of the ACS group was higher than that of the non-CAD group
      at every time point, and the differences were of statistical significance
      (P<0.05). The peak thrombogenic activity of 1*105, 1*104, 1*103 PMPs in ACS
      patients was at 6 min, 8 min, and 11 min respectively, whereas the thrombogenic
      activity of 1*105, 1*104, 1*103 PMPs in non-CAD patients was at 16 min, 21 min,
      and 41 min respectively. CONCLUSION: The levels of platelets and PMPs in ACS
      patients were higher than those in non-CAD patients, implying that rupture of the
      coronary atherosclerotic plaques led to an increase in platelets and the
      subsequent massive release of PMPs by the activated platelets. The plaques in the
      ACS patients are prone to rupture such that the platelets are in an activated
      state and release a large amount of PMPs, therefore promoting thrombosis.

PMID- 28442517
TI  - Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio in Patients
      with Cutaneous Vasculitis.
AB  - BACKGROUND: Vasculitis represents a specific pattern of inflammation of the blood
      vessel wall that can occur in any organ system of the body. The neutrophil to
      lymphocyte ratio (NLR) and red blood cell distribution width (RDW) are currently
      used as markers of inflammation in several diseases. OBJECTIVES: This study
      analyzed C-reactive protein level (CRP), erythrocyte sedimentation rate (ESR),
      white blood cell (WBC), NLR, and RDW in patients who had cutaneous vasculitis, or
      cutaneous vasculitis with systemic involvement, and in healthy controls. METHODS:
      A total of 85 individuals were included in our study: 45 with vasculitis and 40
      healthy controls. Patients who had complete blood count (CBC) analysis, CRP, and
      ESR at the time of skin biopsy were included in the study. NLR was calculated
      from these parameters. RESULTS: NLR, CRP, ESR, and WBC were significantly higher
      in patients with vasculitis than in healthy controls (p<=0.05), but RDW did not
      significantly differ between the two groups. CONCLUSIONS: This study suggests
      that blood NLR may be used for predicting vasculitis, especially cutaneous
      vasculitis with systemic involvement.

PMID- 28442518
TI  - The Relationship of Mean Platelet Volume/Platelet Distribution Width and Duodenal
      Ulcer Perforation.
AB  - BACKGROUND: Duodenal ulcer perforation (DUP) is a severe acute abdominal disease.
      Mean platelet volume (MPV) and platelet distribution width (PDW) are two platelet
      parameters, participating in many inflammatory processes. This study aims to
      investigate the relation of MPV/PDW and DUP. METHODS: A total of 165 patients
      were studied retrospectively, including 21 females and 144 males. The study
      included two groups: 87 normal patients (control group) and 78 duodenal ulcer
      perforation patients (DUP group). Routine blood parameters were collected for
      analysis including white blood cell count (WBC), neutrophil ratio (NR), platelet
      count (PLT), MPV and PDW. Receiver operating curve (ROC) analysis was applied to
      evaluate the parameters' sensitivity. RESULTS: No significant differences were
      observed between the control group and DUP group in age and gender. WBC, NR and
      PDW were significantly increased in the DUP group (P<0.001, respectively); PLT
      and MPV were significantly decreased in the DUP group (P<0.001, respectively)
      compared to controls. MPV had the high sensitivity. CONCLUSIONS: Our results
      suggested a potential association between MPV/PDW and disease activity in DUP
      patients, and high sensitivity of MPV.

PMID- 28442519
TI  - Mucosal Healing at 14 Weeks Predicts better Outcome in Low-dose Infliximab
      Treatment for Chinese Patients with Active Intestinal Behcet's Disease.
AB  - AIMS: To compare the efficacy and the safety of low-dose (3.5 mg/kg) or standard
      dose (5 mg/kg) of infliximab (IFX) for induction and maintenance treatment in
      Chinese patients with intestinal Behcet's disease (BD), and to identify potential
      predictors to corticosteroid-free clinical remission at week 30. METHODS: A
      prospective trial was conducted in 20 patients with moderate-to-severe active
      intestinal BD, followed up for 30 weeks. Ileocolonoscopic examinations were done
      at baseline and week 14. A logistic regression model was used to assess the
      predictors of corticosteroid-free remission at week 30. RESULTS: As the primary
      end point, steroid-free remission at week 30 was observed in 40% and 60% of
      patients who received low and standard doses of IFX, respectively (P>0.371). As
      the secondary end point, the mucosal healing (MH) rates at week 14 were found to
      be 60% for both low and standard doses of IFX. The clinical response rates at
      week 14 and 30 were also similar in both groups. Only MH at week 14 predicted
      steroid-free clinical remission at week 30. CONCLUSIONS: Low-dose of IFX is
      effective and safe for induction and maintenance therapy in patients with active
      intestinal BD. MH at week 14 predicted clinical remission at week 30.

PMID- 28442520
TI  - Development and Application of A Duplex Real-Time RT-PCR Assay for Simultaneous
      Detection of Coxsackievirus A6 and Coxsackievirus A10.
AB  - Hand, foot and mouth disease (HFMD) is a serious public health problem.
      Generally, it is considered that HFMD is mainly caused by enterovirus 71 (EV71)
      and coxsackievirus A16 (CVA16). Nevertheless, the incidence of HFMD caused by
      coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) has increased
      significantly and CVA6 and CVA10 have become major causes of HFMD epidemic. This
      study develops a duplex real-time reverse transcript polymerase chain reaction
      (RT-PCR) assay for simultaneous detection of CVA 6 and CVA 10. The specificity,
      sensitivity, and reproducibility of this assay were analyzed. No cross-reactions
      with other viruses or false positives were observed. The detection limit of this
      assay was as low as 11.935 copies for CVA6 and 17.591 copies for CVA10 per
      reaction (concentration giving a positive duplex real-time RT-PCR result in 95%
      of samples). The coefficients of variation of the intra- and inter-assay
      reproducibility for CVA 6 and CVA 10 were both lower than 2%. Our results showed
      that this duplex real-time RT-PCR assay was a simple, rapid, and cost-effective
      method for simultaneous identification of CVA6 and CVA10.

PMID- 28442521
TI  - Application of Flow Cytometry in the Early Diagnosis of Neonatal Sepsis.
AB  - GOALS: To raise awareness of the utility of flow cytometric detection of
      inflammatory markers in the early diagnosis of neonatal sepsis. PROCEDURES: In
      accordance with the Tollner scoring system, cases with >=10 points are accepted
      as having "clinical sepsis" and cases with 0-4 points as having "no sepsis". The
      study group consisted of 50 newborns with clinical sepsis as well as a control
      group of 50 newborns without sepsis. In all cases, blood counts, C-reactive
      protein (CRP) levels, and procalcitonin (PCT) levels were recorded. Additionally,
      the "cluster of differentiation" (CD)64, CD11b, and CD62L adhesion molecules and
      the presence of the human leukocyte antigen HLA-DR on monocyte and neutrophil
      surfaces were examined by flow cytometry. RESULTS: The levels of acute-phase
      reactants CRP and PCT were significantly higher in the study group than in the
      control group (p<0.05). The cell adhesion molecules CD11b and CD64 and the human
      leukocyte antigen HLA-DR were significantly higher in the study group (p<0.05);
      CD62L levels were similar to those in the control group (p>0.05). Furthermore,
      receiver operating characteristic analysis indicated that neutrophil CD11b
      (nCD11b) is a diagnostic marker for neonatal sepsis (area under the curve [AUC]:
      0.72, 95% confidence interval [CI]: 0.62-0.82, p<0.001). The sensitivity,
      specificity, and positive predictive value (PPV) for nCD11b were 72%, 68%, and
      58.4%, respectively. Similarly, monocyte CD11b (mCD11b) positivity was found to
      be diagnostic (AUC 0.77, 95% CI: 0.68-0.87, p<0.001). The sensitivity and
      specificity for mCD11b were 72% and 68%, respectively. In addition, the
      sensitivity, specificity, and PPV for nHLA-DR were 62%, 60%, and 60.8%,
      respectively. CONCLUSION: In addition to acute-phase proteins, cell surface
      antigens such as CD11b, CD64, and HLA-DR should be used in routine investigations
      for the early diagnosis of neonatal sepsis. Such usage in combination with acute
      phase reactants may enhance diagnostic accuracy.

PMID- 28442522
TI  - Clinical Criteria Correlated with the Incidence of Patients with Non-alcoholic
      Fatty Liver Disease.
AB  - GOALS: In this study, predictive panels were constructed and validated to
      recognize an individual with and without nonalcoholic fatty liver disease (NAFLD)
      based on clinical and biochemical criteria. METHODS: Two hundred and thirty six
      non-alcoholic adults with no chronic viral hepatitis history were recruited from
      a medical center in Taiwan in 2013. All subjects were examined for body mass
      index (BMI), abdominal ultrasonography, blood liver function tests (including
      alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma glutamyl
      transpeptidase [GGT]), blood lipids (total cholesterol [TC] and triglyceride
      [TG]) and blood glucose (BG) tests. RESULTS: NAFLD was observed in 66.97% of
      subjects. BMI (p<0.001), ALT (p<0.001), AST (p=0.014), GGT (p=0.034), TC
      (p=0.026), TG (p<0.001) and BG (p<0.001) were significantly higher for subjects
      with NAFLD than subjects without NAFLD. The BMI results (p<0.001), TG (p<0.001),
      ALT (p<0.001), BG (p<0.001), AST (p=0.001), and GGT (p=0.001) correlated well
      with the extent of NAFLD. The increasing risks of NAFLD are hypertriglyceridemia
      (p<0.001), high ALT (p<0.001), high GGT (p=0.009), and hypercholesterolemia
      (p=0.017). Moreover, NAFLD was observed in 98.5% (p<0.001) of subjects with three
      clinical manifestations of body overweight, hypertriglyceridemia and high ALT.
      Additionally, NAFLD was observed in 96.5% (p<0.001) of subjects with other tri
      criteria (body overweight, hypertriglyceridemia, and hypercholesterolemia), or
      92.6% (p<0.001) of subjects with another tri-criteria (body overweight,
      hypertriglyceridemia, and high GGT). CONCLUSION: The tri-criteria of diagnoses
      can accurately predict the surveillance of NAFLD.

PMID- 28442523
TI  - A Detailed Comparison of Morning and Random Urine Specimen Levels with 24 Hour
      Urinary Excretion Levels of Seven Biochemical Parameters with a Proposed Formula.
AB  - This study aimed to evaluate the validity of the suggested method (SM) to
      estimate the urinary level of seven biochemical parameters within 24 hours with
      an innovative formula using morning and random urine specimens. A total of 133
      clients referring to the laboratory of the Endocrinology & Metabolism Research
      Institute, Tehran University of Medical Sciences, participated voluntarily in the
      investigation with providing three urine samples of 24-hour, morning and random.
      Seven biochemical parameters (calcium, phosphorus, urea, creatinine, uric acid,
      microalbumin and protein) were measured in all three samples. After applying the
      proposed formula and the formula of the parameter-to-creatinine ratio (p/c), the
      results obtained from morning and random samples were compared statistically with
      those of 24-hour urine samples. Compared to the p/c ratio method, nearly all the
      results of the SM were more correlated with the 24-hour method (24-hrM). Among
      the results obtained in the SM, the values of urea, calcium and phosphorus in the
      morning urine and those of uric acid, microalbumin, protein and creatinine in the
      random urine showed higher correlation with the respective results of the 24-hrM.
      The new method seems to be a feasible alternative to the methods of 24-hour and
      p/c ratio for measuring morning values of urea, calcium and phosphorus as well as
      random values of uric acid, microalbumin, protein and creatinine. This method is
      a compromised method when 24 hours urine specimen is impossible to get by certain
      patients.

PMID- 28442524
TI  - Extrauterine Adenomyoma of the Liver in a 50 year old Female with Pelvic
      Endometriosis.
AB  - Extrauterine adenomyomas are defined as circumscribed tumor-like masses
      consisting of smooth muscle tissue, endometrioid glands and stroma. They are
      extremely rare tumors and similar to their uterine counterparts. We report case
      of a 50 year old female with an extrauterine adenomyoma of the liver associated
      with pelvic endometriosis. To the best of our knowledge, only fifteen cases of
      extrauterine adenomyomas have been reported with only one previous case in the
      liver. This is the first case of extrauterine adenomyoma of the liver associated
      with pelvic endometriosis.

PMID- 28442525
TI  - Korean Monozygotic Twins with Lethal Acantholytic Epidermolysis Bullosa Caused by
      Two Novel DSP Mutations.
AB  - Desmoplakin is an essential cytoplasmic plaque protein in desmosomes, and it is
      the major linker between intercellular junctions in the skin and heart. The role
      of desmoplakin is anchoring transmembrane cadherins to cytoplasmic intermediate
      filaments. The desmoplakin gene (DSP) is located on chromosome 6, and six common
      allelic disorders are associated with this gene, including autosomal-dominant or 
      recessive disorders that affect the skin, heart, hair, and nails. In particular,
      lethal acantholytic epidermolysis bullosa (LAEB) is an autosomal recessively
      inherited and extremely rare genetic skin disorder, and only three molecularly
      confirmed families with LAEB have been reported previously. Generalized oozing
      erosion of the entire skin is the main clinical feature, which leads to excessive
      transcutaneous fluid loss and neonatal death. Histopathologically, this disorder
      is classified as a suprabasal subtype of epidermolysis bullosa simplex. In this
      study, we report for the first time in Korea on monozygotic twins with LAEB
      caused by two novel nonsense mutations in the DSP gene. Both of the twins
      exhibited severe and rapid progressive whole body skin erosion, and they died
      shortly after birth because of multiorgan failure followed by excessive fluid
      loss.

PMID- 28442526
TI  - Morphoproteomic-Guided Treatment of Chemotherapy Resistant Colon Cancer using
      Natural Based Therapies: A Case Study.
AB  - Colorectal cancer was estimated to have the fourth newest incident rate and to
      have the second highest death rate in 2015 according to the American Cancer
      Society. There were an estimated 132,700 new diagnoses of colorectal cancer made
      and approximately 69,000 deaths in 2015 attributing to this form of cancer. 5
      fluorouracil (5-FU) or 5-FU with oxaliplatin (FOLFOX) continues to be the
      standard treatment protocol for patients presenting with colorectal cancer.
      However, treatment with FOLFOX and conventional chemotherapy has shown to lead to
      cancer recurrence and a number of toxic side effects. Alternative therapies based
      on natural ingredients show promise in combating cancer by inhibiting tumorigenic
      pathways, such as mTORC (mammalian target of rapamycin complex), c-MYC oncogene,
      and the COX-2 pathway. Using natural based agents and morphoproteomic-guided
      targeted therapy, the goal of this study was to evaluate the effectiveness of
      such an approach in a chemotherapy resistant, colon cancer patient. This case
      report describes a 46-year old woman with a non-metastasizing colorectal cancer
      that showed "minimal treatment effect" with chemotherapy despite being compliant.
      As of May 2016, CT scans and colonoscopy confirmed that the cancer was in
      remission after that patient had been compliant with morphoproteomic-guided,
      natural therapies for nine months.

PMID- 28442527
TI  - A Novel Fibrillin-1 Gene Mutation Leading to Marfan Syndrome in a Korean Girl.
AB  - Marfan syndrome is an autosomal dominant genetic disorder caused by a connective
      tissue defect. A nine-year-old girl was referred to our pediatric endocrinology
      clinic for tall stature. Physical examination revealed a lens dislocation with
      strabismus, high palate, positive wrist and thumb signs, joint hypermobility, and
      pes planus. Transthoracic echocardiography revealed dilatation of the aortic
      root. She was diagnosed with Marfan syndrome based on the revised Ghent
      diagnostic criteria. Molecular investigation identified a heterozygous c.2810G >A
      variation in the FBN1 gene in the patient, but not in her parents. To our
      knowledge, this sequence variant has been reported as a polymorphism
      (rs113602180), but it is the first report identifying it as the genetic cause of
      Marfan syndrome. We hypothesize that this de novo novel missense FBN1 mutation
      disrupts fibrillin-1 function and is probably involved in the development of
      Marfan syndrome in this patient.

PMID- 28442528
TI  - Inflammatory Bowel Disease and Immune Thrombocytopenic Purpura: Combined Immune
      Dysregulation in an Adolescent.
AB  - Concomitant inflammatory bowel disease (IBD) and immune thrombocytopenic purpura
      (ITP) is a rare phenomenon. A shared immunologic pathway leading to mucosal
      inflammation and platelet destruction has been proposed. We report a case of a 14
      year-old male who presented with abdominal pain, hematochezia, weight loss, and
      thrombocytopenia. Endoscopic and hematologic evaluations led to the diagnosis of
      ulcerative colitis (UC) and ITP, respectively. Initial treatment of his UC
      resulted in improvement in both gastrointestinal symptoms and platelet count.
      Management of this case, however, was complicated by inconsistent correlation
      between UC symptoms and platelet count throughout his clinical course. The co
      occurrence of IBD and ITP is an important entity, albeit rare, which needs to be
      considered when evaluating a patient with hematochezia and thrombocytopenia.

PMID- 28442529
TI  - Coinheritance of Novel Mutations in SCN1A Causing GEFS+ and in KDM6A Causing
      Kabuki Syndrome in a Family.
AB  - Because the differentiation between phenotypic expansion and blended phenotypes
      is not clear, the mixed phenotypes of blended rare genetic diseases make
      diagnosis difficult. We describe a family with the co-existence and co
      segregation of generalized epilepsy with febrile seizures plus (GEFS+) and Kabuki
      syndrome (KS). The proband, a 7-year-old male, presented with GEFS+, dysmorphic
      facial features, short stature, developmental delay, and intellectual disability.
      Two novel missense mutations: p.G325A in the KDM6A gene responsible for KS and
      p.G1877V in the SCN1A gene responsible for GEFS+ were identified using the
      TruSight One sequencing panel. This family is the first in the literature to be
      confirmed molecularly with the blended phenotype of GEFS+ and KS. Furthermore,
      two affected female patients with X-linked KS showed a partial escape X
      inactivation pattern of KDM6A with milder phenotypes than the male affected
      proband in this study.

PMID- 28442530
TI  - Breach of autoreactive B cell tolerance by post-translationally modified
      proteins.
AB  - OBJECTIVES: Over 50% of patients with rheumatoid arthritis (RA) harbour a variety
      of anti-modified protein antibodies (AMPA) against different post-translationally
      modified (PTM) proteins, including anti-carbamylated protein (anti-CarP)
      antibodies. At present, it is unknown how AMPA are generated and how autoreactive
      B cell responses against PTM proteins are induced. Here we studied whether PTM
      foreign antigens can breach B cell tolerance towards PTM self-proteins. METHODS:
      Serum reactivity towards five carbamylated proteins was determined for 160
      patients with RA and 40 healthy individuals. Antibody cross-reactivity was
      studied by inhibition experiments. Mass spectrometry was performed to identify
      carbamylated self-proteins in human rheumatic joint tissue. Mice were immunised
      with carbamylated or non-modified (auto)antigens and analysed for autoantibody
      responses. RESULTS: We show that anti-CarP antibodies in RA are highly cross
      reactive towards multiple carbamylated proteins, including modified self-proteins
      and modified non-self-proteins. Studies in mice show that anti-CarP antibody
      responses recognising carbamylated self-proteins are induced by immunisation with
      carbamylated self-proteins and by immunisation with carbamylated proteins of non
      self-origin. Similar to the data observed with sera from patients with RA, the
      murine anti-CarP antibody response was, both at the monoclonal level and the
      polyclonal level, highly cross-reactive towards multiple carbamylated proteins,
      including carbamylated self-proteins. CONCLUSIONS: Self-reactive AMPA responses
      can be induced by exposure to foreign proteins containing PTM. These data show
      how autoreactive B cell responses against PTM self-proteins can be induced by
      exposure to PTM foreign proteins and provide new insights on the breach of
      autoreactive B cell tolerance.

PMID- 28442531
TI  - Gene body DNA methylation conspires with H3K36me3 to preclude aberrant
      transcription.

PMID- 28442532
TI  - Anti-inflammatory effects of simvastatin during the resolution phase of
      experimentally formed venous thrombi.
AB  - Deep venous thrombosis (DVT) is a common vascular disease and is closely linked
      to inflammation. Over the past decade, the potential antithrombotic effect of
      statins has been elucidated by clinical studies, primarily through focusing on
      DVT prevention. The effects of statins on DVT resolution and its underlying
      mechanisms have been rarely addressed. We established a rabbit model of the
      inferior vena cava (IVC) venous thrombosis. After 48 hours, the rabbits were
      treated with saline, heparin, simvastatin, or simvastatin combined with heparin,
      respectively, for 14 days. The migration of inflammatory cells (neutrophils,
      monocytes, lymphocytes) in the thrombi and injured venous wall, the plasma levels
      of interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1) and P-selectin, and
      local expression of MCP-1 and P-selectin in the venous wall were evaluated by
      histology, immunohistochemistry, and ELISA examinations. Our data showed that
      compared with saline and heparin controls, monotherapy of simvastatin and the
      adjunctive therapy with simvastatin and heparin significantly improved the
      thrombus resolution and reduced inflammatory cells migration into the venous
      wall, the release of the inflammatory cell adhesion molecule (P-selectin),
      inflammatory chemokine (MCP-1) and pleiotropic proinflammatory cytokines (IL-6)
      into the blood, and the local expression of P-selectin and MCP-1 in the venous
      wall. Simvastatin targets anti-inflammatory pathways during the resolution phase
      of a thrombus, providing a therapeutic potential in DVT resolution and post
      thrombotic syndrome prevention.

PMID- 28442533
TI  - Racial disparities in stage-specific gastric cancer: analysis of results from the
      Surveillance Epidemiology and End Results (SEER) program database.
AB  - The incidence of gastric cancer is declining in western countries but continues
      to represent a serious health problem worldwide, especially in Asia and among
      Asian Americans. This study aimed to investigate ethnic disparities in stage
      specific gastric cancer, including differences in incidence, treatment and
      survival. The cohort study was analyzed using the data set of patients with
      gastric cancer registered in the Surveillance, Epidemiology, and End Results
      (SEER) program from 2004 to 2013. Among 54,165 patients with gastric cancer,
      38,308 were whites (70.7%), 7546 were blacks (13.9%), 494 were American
      Indian/Alaskan Natives (0.9%) and 7817 were Asians/Pacific Islanders (14.4%).
      Variables were patient demographics, disease characteristics, surgery/radiation
      treatment, overall survival (OS) and cause specific survival (CSS).
      Asians/Pacific Islanders demonstrated the highest incidence rates for gastric
      cancer compared with other groups and had the greatest decline in incidence
      during the study period (13.03 to 9.28 per 100,000/year), as well as the highest
      percentage of patients with American Joint Committee on Cancer (AJCC) early stage
      gastric cancer. There were significant differences between groups in treatment
      across stages I-IV (all p<0.001); Asians/Pacific Islanders had the highest rate
      of surgery plus radiation (45.1%). Significant differences were found in OS and
      CSS between groups (p<0.001); OS was highest among Asians/Pacific Islanders.
      Multivariate analysis revealed that age, race, grade, stage, location, and second
      primary cancer were valid prognostic factors for survival. Marked ethnic
      disparities exist in age-adjusted incidence of primary gastric cancer, with
      significant differences between races in age, gender, histological type, grade,
      AJCC stage, location, second cancer, treatment and survival.

PMID- 28442534
TI  - Oncogenic beta-catenin and PIK3CA instruct network states and cancer phenotypes
      in intestinal organoids.
AB  - Colorectal cancer is driven by cooperating oncogenic mutations. In this study, we
      use organotypic cultures derived from transgenic mice inducibly expressing
      oncogenic beta-catenin and/or PIK3CAH1047R to follow sequential changes in cancer
      related signaling networks, intestinal cell metabolism, and physiology in a three
      dimensional environment mimicking tissue architecture. Activation of beta-catenin
      alone results in the formation of highly clonogenic cells that are nonmotile and
      prone to undergo apoptosis. In contrast, coexpression of stabilized beta-catenin
      and PIK3CAH1047R gives rise to intestinal cells that are apoptosis-resistant,
      proliferative, stem cell-like, and motile. Systematic inhibitor treatments of
      organoids followed by quantitative phenotyping and phosphoprotein analyses
      uncover key changes in the signaling network topology of intestinal cells after
      induction of stabilized beta-catenin and PIK3CAH1047R We find that survival and
      motility of organoid cells are associated with 4EBP1 and AKT phosphorylation,
      respectively. Our work defines phenotypes, signaling network states, and
      vulnerabilities of transgenic intestinal organoids as a novel approach to
      understanding oncogene activities and guiding the development of targeted
      therapies.

PMID- 28442535
TI  - Multiple kinesin-14 family members drive microtubule minus end-directed transport
      in plant cells.
AB  - Minus end-directed cargo transport along microtubules (MTs) is exclusively driven
      by the molecular motor dynein in a wide variety of cell types. Interestingly,
      during evolution, plants have lost the genes encoding dynein; the MT motors that
      compensate for dynein function are unknown. Here, we show that two members of the
      kinesin-14 family drive minus end-directed transport in plants. Gene knockout
      analyses of the moss Physcomitrella patens revealed that the plant-specific class
      VI kinesin-14, KCBP, is required for minus end-directed transport of the nucleus
      and chloroplasts. Purified KCBP directly bound to acidic phospholipids and
      unidirectionally transported phospholipid liposomes along MTs in vitro. Thus,
      minus end-directed transport of membranous cargoes might be driven by their
      direct interaction with this motor protein. Newly nucleated cytoplasmic MTs
      represent another known cargo exhibiting minus end-directed motility, and we
      identified the conserved class I kinesin-14 (ATK) as the motor involved. These
      results suggest that kinesin-14 motors were duplicated and developed as
      alternative MT-based minus end-directed transporters in land plants.

PMID- 28442536
TI  - TANGO1 recruits Sec16 to coordinately organize ER exit sites for efficient
      secretion.
AB  - Mammalian endoplasmic reticulum (ER) exit sites export a variety of cargo
      molecules including oversized cargoes such as collagens. However, the mechanisms
      of their assembly and organization are not fully understood. TANGO1L is
      characterized as a collagen receptor, but the function of TANGO1S remains to be
      investigated. Here, we show that direct interaction between both isoforms of
      TANGO1 and Sec16 is not only important for their correct localization but also
      critical for the organization of ER exit sites. The depletion of TANGO1
      disassembles COPII components as well as membrane-bound ER-resident complexes,
      resulting in fewer functional ER exit sites and delayed secretion. The
      ectopically expressed TANGO1 C-terminal domain responsible for Sec16 binding in
      mitochondria is capable of recruiting Sec16 and other COPII components. Moreover,
      TANGO1 recruits membrane-bound macromolecular complexes consisting of cTAGE5 and
      Sec12 to the ER exit sites. These data suggest that mammalian ER exit sites are
      organized by TANGO1 acting as a scaffold, in cooperation with Sec16 for efficient
      secretion.

PMID- 28442537
TI  - Age-Related Reversals in Neural Recruitment across Memory Retrieval Phases.
AB  - Over the last several decades, neuroimaging research has identified age-related
      neural changes that occur during cognitive tasks. These changes are used to help
      researchers identify functional changes that contribute to age-related
      impairments in cognitive performance. One commonly reported example of such a
      change is an age-related decrease in the recruitment of posterior sensory regions
      coupled with an increased recruitment of prefrontal regions across multiple
      cognitive tasks. This shift is often described as a compensatory recruitment of
      prefrontal regions due to age-related sensory-processing deficits in posterior
      regions. However, age is not only associated with spatial shifts in recruitment,
      but also with temporal shifts, in which younger and older adults recruit the same
      neural region at different points in a task trial. The current study examines the
      possible contribution of temporal modifications in the often-reported posterior
      anterior shift. Participants, ages 19-85, took part in a memory retrieval task
      with a protracted retrieval trial consisting of an initial memory search phase
      and a subsequent detail elaboration phase. Age-related neural patterns during
      search replicated prior reports of age-related decreases in posterior recruitment
      and increases in prefrontal recruitment. However, during the later elaboration
      phase, the same posterior regions were associated with age-related increases in
      activation. Further, ROI and functional connectivity results suggest that these
      posterior regions function similarly during search and elaboration. These results
      suggest that the often-reported posterior-anterior shift may not reflect the
      inability of older adults to engage in sensory processing, but rather a change in
      when they recruit this processing.SIGNIFICANCE STATEMENT The current study
      provides evidence that the often-reported posterior-anterior shift in aging may
      not reflect a global sensory-processing deficit, as has often been reported, but
      rather a temporal modification in this processing in which older adults engage
      the same neural regions during a detail elaboration phase that younger adults
      engage during memory search. In other words, older adults may ultimately be able
      to engage the same processes as younger adults during some cognitive tasks when
      given the time to do so. Future research should examine the generalizability of
      this effect and the importance of encouraging older adults to engage in these
      processes through task instruction or questions.

PMID- 28442538
TI  - Peripheral Tumor Necrosis Factor-Alpha (TNF-alpha) Modulates Amyloid Pathology by
      Regulating Blood-Derived Immune Cells and Glial Response in the Brain of AD/TNF
      Transgenic Mice.
AB  - Increasing evidence has suggested that systemic inflammation along with local
      brain inflammation can play a significant role in Alzheimer's disease (AD)
      pathogenesis. Identifying key molecules that regulate the crosstalk between the
      immune and the CNS can provide potential therapeutic targets. TNF-alpha is a
      proinflammatory cytokine implicated in the pathogenesis of systemic inflammatory
      and neurodegenerative diseases, such as rheumatoid arthritis (RA) and AD. Recent
      studies have reported that anti-TNF-alpha therapy or RA itself can modulate AD
      pathology, although the underlying mechanism is unclear. To investigate the role
      of peripheral TNF-alpha as a mediator of RA in the pathogenesis of AD, we
      generated double-transgenic 5XFAD/Tg197 AD/TNF mice that develop amyloid deposits
      and inflammatory arthritis induced by human TNF-alpha (huTNF-alpha) expression.
      We found that 5XFAD/Tg197 mice display decreased amyloid deposition, compromised
      neuronal integrity, and robust brain inflammation characterized by extensive
      gliosis and elevated blood-derived immune cell populations, including phagocytic
      macrophages and microglia. To evaluate the contribution of peripheral huTNF-alpha
      in the observed brain phenotype, we treated 5XFAD/Tg197 mice systemically with
      infliximab, an anti-huTNF-alpha antibody that does not penetrate the blood-brain
      barrier and prevents arthritis. Peripheral inhibition of huTNF-alpha increases
      amyloid deposition, rescues neuronal impairment, and suppresses gliosis and
      recruitment of blood-derived immune cells, without affecting brain huTNF-alpha
      levels. Our data report, for the first time, a distinctive role for peripheral
      TNF-alpha in the modulation of the amyloid phenotype in mice by regulating blood
      derived and local brain inflammatory cell populations involved in beta-amyloid
      clearance.SIGNIFICANCE STATEMENT Mounting evidence supports the active
      involvement of systemic inflammation, in addition to local brain inflammation, in
      Alzheimer's disease (AD) progression. TNF-alpha is a pluripotent cytokine that
      has been independently involved in the pathogenesis of systemic inflammatory
      rheumatoid arthritis (RA) and AD. Here we first demonstrate that manipulation of
      peripheral TNF-alpha in the context of arthritis modulates the amyloid phenotype
      by regulating immune cell trafficking in the mouse brain. Our study suggests that
      additionally to its local actions in the AD brain, TNF-alpha can also indirectly
      modulate amyloid pathology as a regulator of peripheral inflammation. Our
      findings may have significant implications in the treatment of RA patients with
      anti-TNF-alpha drugs and in the potential use of TNF-targeted therapies for AD.

PMID- 28442539
TI  - Retraction for McCarthy et al., "The Ax21 Protein Is a Cell-Cell Signal That
      Regulates Virulence in the Nosocomial Pathogen Stenotrophomonas maltophilia".

PMID- 28442541
TI  - Respiratory Scores as a Tool to Reduce Bronchodilator Use in Children
      Hospitalized With Acute Viral Bronchiolitis.
AB  - BACKGROUND AND OBJECTIVES: Adoption of clinical respiratory scoring as a quality
      improvement (QI) tool in bronchiolitis has been temporally associated with
      decreased bronchodilator usage. We sought to determine whether documented use of
      a clinical respiratory score at the patient level was associated with a decrease
      in either the physician prescription of any dose of bronchodilator or the number
      of doses, if prescribed, in a multisite QI collaborative. METHODS: We performed a
      secondary analysis of data from a QI collaborative involving 22 hospitals. The
      project enrolled patients aged 1 month to 2 years with a primary diagnosis of
      acute viral bronchiolitis and excluded those with prematurity, other significant
      comorbid diseases, and those needing intensive care. We assessed for an
      association between documentation of any respiratory score use during an episode
      of care, as well as the method in which scores were used, and physician
      prescribing of any bronchodilator and number of doses. Covariates considered were
      phase of the collaborative, hospital length of stay, steroid use, and presence of
      household smokers. RESULTS: A total of 1876 subjects were included. There was no
      association between documentation of a respiratory score and the likelihood of
      physician prescribing of any bronchodilator. Score use was associated with fewer
      doses of bronchodilators if one was prescribed (P = .05), but this association
      disappeared with multivariable analysis (P = .73). CONCLUSIONS: We found no clear
      association between clinical respiratory score use and physician prescribing of
      bronchodilators in a multicenter QI collaborative.

PMID- 28442542
TI  - Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis
      pigmentosa.
AB  - BACKGROUND: Recent findings suggesting that Abelson helper integration site 1
      (AHI1) is involved in non-syndromic retinal disease have been debated, as the
      functional significance of identified missense variants was uncertain. We
      assessed whether AHI1 variants cause non-syndromic retinitis pigmentosa (RP).
      METHODS: Exome sequencing was performed in three probands with RP. The effects of
      the identified missense variants in AHI1 were predicted by three-dimensional
      structure homology modelling. Ciliary parameters were evaluated in patient's
      fibroblasts, and recombinant mutant proteins were expressed in ciliated retinal
      pigmented epithelium cells. RESULTS: In the three patients with RP, three sets of
      compound heterozygous variants were detected in AHI1 (c.2174G>A; p.Trp725* and
      c.2258A>T; p.Asp753Val, c.660delC; p.Ser221Glnfs*10 and c.2090C>T; p.Pro697Leu,
      c.2087A>G; p.His696Arg and c.2429C>T; p.Pro810Leu). All four missense variants
      were present in the conserved WD40 domain of Jouberin, the ciliary protein
      encoded by AHI1, with variable predicted implications for the domain structure.
      No significant changes in the percentage of ciliated cells, nor in cilium length
      or intraflagellar transport were detected. However, expression of mutant
      recombinant Jouberin in ciliated cells showed a significantly decreased
      enrichment at the ciliary base. CONCLUSIONS: This report confirms that mutations
      in AHI1 can underlie autosomal recessive RP. Moreover, it structurally and
      functionally validates the effect of the RP-associated AHI1 variants on protein
      function, thus proposing a new genotype-phenotype correlation for AHI1 mutation
      associated retinal ciliopathies.

PMID- 28442543
TI  - Effect of informal employment on the relationship between psychosocial work risk
      factors and musculoskeletal pain in Central American workers.
AB  - INTRODUCTION: The constant increase on the psychosocial demands experienced at
      work seems to contribute to the increase in health problems such as
      musculoskeletal pain (MSP). This association may be especially important in low
      income and middle-income countries, where there is a large proportion of informal
      workers among whom there is little research. We analysed the association between
      psychosocial work risk factors and MSP among formal and informal workers using
      the First Central American Survey of Working Conditions and Health. METHODS: This
      is a representative sample (n=12 024) of the economically active population of
      the six Spanish-speaking countries of Central America. Prevalence ratios (PR) and
      corresponding 95% CIs from Poisson regression models were used to estimate the
      association between psychosocial work risk factors and the MSP. RESULTS: Compared
      with formal workers, informal workers reported higher prevalence of MPS in the
      body regions analysed (ie, cervicodorsal, lumbosacral, upper extremities) and
      higher exposure to psychosocial work risk factors. However, on the whole, the
      associations between the exposure to psychosocial work risk factors and the
      prevalence of MSP were similar for both formal and informal workers. Only the
      association between exposure to high demands and MSP in the upper extremities was
      higher (p=0.012) among formal (PR=1.69, 95% CI 1.46 to 1.96) than among informal
      workers (PR=1.40; 95% CI 1.30 to 1.51). CONCLUSION: Exposure to adverse levels of
      psychosocial work risk factors is associated with higher prevalence of MPS among
      both formal and informal workers. However, the role of employment informality in
      this association is complex and requires further examination.

PMID- 28442544
TI  - Effects of aircraft noise exposure on saliva cortisol near airports in France.
AB  - BACKGROUND: Saliva cortisol is a possible marker of noise-induced stress and
      could then mediate the relation observed between exposure to aircraft or road
      traffic noise and cardiovascular diseases. However, the association between
      transportation noise and cortisol levels is still unclear. The objective of the
      study was to investigate the variability of saliva cortisol concentration as an
      indicator of disturbed hypothalamus-pituitary-adrenal (HPA) axis regulation in
      relation to long-term aircraft noise exposure. METHODS: Saliva samples were taken
      when awakening and before going to bed for 1244 participants older than 18 years
      of age. Information about health, socioeconomic and lifestyle factors was also
      collected by means of a face-to-face questionnaire performed at home by an
      interviewer. Aircraft noise exposure was assessed for each participant's home
      address using noise maps. Linear regression models were used to evaluate the
      effects of aircraft noise exposure on the morning and evening cortisol levels and
      on the daily variation of cortisol per hour. RESULTS: This study suggests a
      modification of the cortisol circadian rhythm in relation to aircraft noise
      exposure. This exposure was associated with a smaller variation of cortisol
      levels over the day, with unchanged morning cortisol levels, but higher cortisol
      levels in the evening. CONCLUSIONS: These findings provide some support for a
      psychological stress induced by aircraft noise exposure, resulting in HPA
      dysregulation and a flattened cortisol rhythm, thus contributing to
      cardiovascular diseases.

PMID- 28442546
TI  - Modeled structural basis for the recognition of alpha2-3-sialyllactose by soluble
      Klotho.
AB  - Soluble Klotho (sKlotho) is the shed ectodomain of antiaging membrane Klotho that
      contains 2 extracellular domains KL1 and KL2, each of which shares sequence
      homology to glycosyl hydrolases. sKlotho elicits pleiotropic cellular responses
      with a poorly understood mechanism of action. Notably, in injury settings,
      sKlotho confers cardiac and renal protection by down-regulating calcium-permeable
      transient receptor potential canonical type isoform 6 (TRPC6) channels in
      cardiomyocytes and glomerular podocytes. Inhibition of PI3K-dependent exocytosis
      of TRPC6 is thought to be the underlying mechanism, and recent studies showed
      that sKlotho interacts with alpha2-3-sialyllactose-containing gangliosides
      enriched in lipid rafts to inhibit raft-dependent PI3K signaling. However, the
      structural basis for binding and recognition of alpha2-3-sialyllactose by sKlotho
      is unknown. Using homology modeling followed by docking, we identified key
      protein residues in the KL1 domain that are likely involved in binding
      sialyllactose. Functional experiments based on the ability of Klotho to down
      regulate TRPC6 channel activity confirm the importance of these residues.
      Furthermore, KL1 domain binds alpha2-3-sialyllactose, down-regulates TRPC6
      channels, and exerts protection against stress-induced cardiac hypertrophy in
      mice. Our results support the notion that sialogangliosides and lipid rafts are
      membrane receptors for sKlotho and that the KL1 domain is sufficient for the
      tested biologic activities. These findings can help guide the design of a simpler
      Klotho mimetic.-Wright, J. D., An, S.-W., Xie, J., Yoon, J., Nischan, N., Kohler,
      J. J., Oliver, N., Lim, C., Huang, C.-L. Modeled structural basis for the
      recognition of alpha2-3-sialyllactose by soluble Klotho.

PMID- 28442545
TI  - Peroxisome proliferator-activated receptor-gamma agonists attenuate biofilm
      formation by Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a significant contributor to recalcitrant multidrug
      resistant infections, especially in immunocompromised and hospitalized patients.
      The pathogenic profile of P. aeruginosa is related to its ability to secrete a
      variety of virulence factors and to promote biofilm formation. Quorum sensing
      (QS) is a mechanism wherein P. aeruginosa secretes small diffusible molecules,
      specifically acyl homo serine lactones, such as N-(3-oxo-dodecanoyl)-l-homoserine
      lactone (3O-C12-HSL), that promote biofilm formation and virulence via
      interbacterial communication. Strategies that strengthen the host's ability to
      inhibit bacterial virulence would enhance host defenses and improve the treatment
      of resistant infections. We have recently shown that peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists are potent immunostimulators that
      play a pivotal role in host response to virulent P. aeruginosa Here, we show that
      QS genes in P. aeruginosa (strain PAO1) and 3O-C12-HSL attenuate PPARgamma
      expression in bronchial epithelial cells. PAO1 and 3O-C12-HSL induce barrier
      derangements in bronchial epithelial cells by lowering the expression of
      junctional proteins, such as zonula occludens-1, occludin, and claudin-4.
      Expression of these proteins was restored in cells that were treated with
      pioglitazone, a PPARgamma agonist, before infection with PAO1 and 3O-C12-HSL.
      Barrier function and bacterial permeation studies that have been performed in
      primary human epithelial cells showed that PPARgamma agonists are able to restore
      barrier integrity and function that are disrupted by PAO1 and 3O-C12-HSL.
      Mechanistically, we show that these effects are dependent on the induction of
      paraoxonase-2, a QS hydrolyzing enzyme, that mitigates the effects of QS
      molecules. Importantly, our data show that pioglitazone, a PPARgamma agonist,
      significantly inhibits biofilm formation on epithelial cells by a mechanism that
      is mediated via paraoxonase-2. These findings elucidate a novel role for
      PPARgamma in host defense against P. aeruginosa Strategies that activate
      PPARgamma can provide a therapeutic complement for treatment of resistant P.
      aeruginosa infections.-Bedi, B., Maurice, N. M., Ciavatta, V. T., Lynn, K. S.,
      Yuan, Z., Molina, S. A., Joo, M., Tyor, W. R., Goldberg, J. B., Koval, M., Hart,
      C. M., Sadikot, R. T. Peroxisome proliferator-activated receptor-gamma agonists
      attenuate biofilm formation by Pseudomonas aeruginosa.

PMID- 28442548
TI  - Keratin 8/18 regulation of insulin receptor signaling and trafficking in
      hepatocytes through a concerted phosphoinositide-dependent Akt and Rab5
      modulation.
AB  - Keratins (Ks) are epithelial cell intermediate filament (IF) proteins that are
      expressed as pairs in a differentiation-regulated manner. Hepatocyte IFs are made
      only of K8/K18 pairs, which means that a K8 loss in K8-null mice leads to
      degradation of K18. Functionally, there is accumulating evidence that IFs
      contribute to signaling platforms. Here, we investigate the role of K8/K18 IFs in
      the regulation of insulin receptor (IR) signaling and trafficking in hepatocytes.
      We find that the IR substrate 1 (IRS1)/PI3K/Akt signaling cascade-downstream of
      IR-displays prolonged activation in K8-null compared with wild-type hepatocytes.
      Assessment of the Akt/mammalian target of rapamycin complex 1-mediated feedback
      loop to IRS1/PI3K, in the absence or presence of drug inhibitors, further
      supports a preferential K8/K18 IF intervention at the surface membrane. In K8
      null hepatocytes, IR trafficking vesicles that are labeled by
      Rab5/EEA1/phosphatidylinositol 3-phosphate accumulate at a juxtanuclear region
      via a microtubule-dependent process. Moreover, interference with
      phosphatidylinositol 4,5-biphosphate signaling aggravates IR/Rab5 accumulation.
      Overall, results uncover K8/K18 IF regulation of IR signaling via a concerted
      modulation of phosphatidylinositol 4,5-biphosphate-dependent IRS1/PI3K/Akt
      signaling and Rab5/phosphatidylinositol 3-phosphate/microtubule trafficking in
      hepatocytes.-Roux, A., Loranger, A., Lavoie, J. N., Marceau, N. Keratin 8/18
      regulation of insulin receptor signaling and trafficking in hepatocytes through a
      concerted phosphoinositide-dependent Akt and Rab5 modulation.

PMID- 28442547
TI  - Biosynthesis of proresolving lipid mediators by vascular cells and tissues.
AB  - Recent evidence suggests that specialized proresolving lipid mediators (SPMs)
      generated from docosahexaenoic acid (DHA) can modulate the vascular injury
      response. However, cellular sources for these autacoids within the vessel wall
      remain unclear. Here, we investigated whether isolated vascular cells and tissues
      can produce SPMs and assessed expression and subcellular localization of the key
      SPM biosynthetic enzyme 5-lipoxygenase (LOX) in vascular cells. Intact human
      arteries incubated with DHA ex vivo produced 17-hydroxy DHA (17-HDHA) and D
      series resolvins, as assessed by liquid chromatography-tandem mass spectrometry.
      Addition of 17-HDHA to human arteries similarly increased resolvin production.
      Primary cultures of human saphenous vein endothelial cells (ECs) and vascular
      smooth muscle cells (VSMCs) converted 17-HDHA to SPMs, including resolvin D1
      (RvD1) and other D-series resolvins and protectins. This was accompanied by a
      rapid translocation of 5-LOX from nucleus to cytoplasm in both ECs and VSMCs,
      potentially facilitating SPM biosynthesis. Conditioned medium from cells exposed
      to 17-HDHA inhibited monocyte adhesion to TNF-alpha-stimulated EC monolayers.
      These downstream effects were partially reversed by antibodies against the RvD1
      receptors ALX/FPR2 and GPR32. These results suggest that autocrine and/or
      paracrine signaling via locally generated SPMs in the vasculature may represent a
      novel homeostatic mechanism of relevance to vascular health and disease.
      Chatterjee, A., Komshian, S., Sansbury, B. E., Wu, B., Mottola, G., Chen, M.,
      Spite, M., Conte, M. S. Biosynthesis of proresolving lipid mediators by vascular
      cells and tissues.

PMID- 28442550
TI  - Withholding treatment: What, Whom and Why?

PMID- 28442549
TI  - Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain
      gangliosides.
AB  - Gangliosides (sialylated glycolipids) play an essential role in the CNS by
      regulating recognition and signaling in neurons. Metabolic blocks in processing
      and catabolism of gangliosides result in the development of severe neurologic
      disorders, including gangliosidoses manifesting with neurodegeneration and
      neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and
      4, play important roles in catabolic processing of brain gangliosides by cleaving
      terminal sialic acid residues in their glycan chains. In neuraminidase 3 and 4
      double-knockout mice, GM3 ganglioside is stored in microglia, vascular pericytes,
      and neurons, causing micro- and astrogliosis, neuroinflammation, accumulation of
      lipofuscin bodies, and memory loss, whereas their cortical and hippocampal
      neurons have lower rate of neuritogenesis in vitro Double-knockout mice also have
      reduced levels of GM1 ganglioside and myelin in neuronal axons. Furthermore,
      neuraminidase 3 deficiency drastically increased storage of GM2 in the brain
      tissues of an asymptomatic mouse model of Tay-Sachs disease, a severe human
      gangliosidosis, indicating that this enzyme is responsible for the metabolic
      bypass of beta-hexosaminidase A deficiency. Together, our results provide the
      first in vivo evidence that neuraminidases 3 and 4 have important roles in CNS
      function by catabolizing gangliosides and preventing their storage in lipofuscin
      bodies.-Pan, X., De Britto Para De Aragao, C., Velasco-Martin, J. P., Priestman,
      D. A., Wu, H. Y., Takahashi, K., Yamaguchi, K., Sturiale, L., Garozzo, D., Platt,
      F. M., Lamarche-Vane, N., Morales, C. R., Miyagi, T., Pshezhetsky, A. V.
      Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain
      gangliosides.

PMID- 28442551
TI  - The case for and against harm reduction approaches to drugs in sport.

PMID- 28442552
TI  - The role of anticipated decision regret and the patient's best interest in
      sterilisation and medically assisted reproduction.
AB  - There is a clear discrepancy in the way those who request medical assistance in
      pursuit of their reproductive choices are treated. On the one hand, women who
      request a sterilisation are urged to consider possible future regrets and are
      sometimes refused treatment in anticipation of such regrets. This is despite the
      fact that for all age ranges, the majority of women undergoing a sterilisation do
      not regret the decision. Moreover, women who are voluntarily childless are likely
      to have a happier and more gratifying life than parents. On the other hand, women
      who request fertility treatment are not urged to second guess their desire for
      parenthood. Although the fact that the probability of regret is expected to be
      higher in the former case than in the latter justifies this difference in
      treatment to a certain extent, the gap between the two different approaches is
      wider than it ought to be if we also take future well-being into consideration,
      instead of focussing exclusively on anticipated decision regret.

PMID- 28442554
TI  - Exposure of patients to ionising radiation during lung cancer diagnostic work-up.
AB  - We examined the dose of radiation received during diagnosis of lung cancer as
      this may add to the risk of a second primary cancer. Patients undergoing surgery
      (n=40) or (chemo)radiotherapy (n=40) received comparable doses (28.6 and 25.8
      mSv, respectively), significantly higher than that for supportive care (n=40;
      15.1 mSv). The effective dose of radiation received was higher for early stage
      disease than for those with metastatic disease. The mean lifetime attributable
      risk of malignancy for those receiving treatment with curative intent in our
      cohort was 0.059%, and lung-specific risk 0.019%.

PMID- 28442555
TI  - Ambient particulate matter and COPD in China: a challenge for respiratory health
      research.

PMID- 28442553
TI  - NLRP3 signaling drives macrophage-induced adaptive immune suppression in
      pancreatic carcinoma.
AB  - The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is
      characterized by immune tolerance, which enables disease to progress unabated by
      adaptive immunity. However, the drivers of this tolerogenic program are
      incompletely defined. In this study, we found that NLRP3 promotes expansion of
      immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the
      differentiation of CD4+ T cells into tumor-promoting T helper type 2 cell (Th2
      cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell
      polarization and cytotoxic CD8+ T cell activation. The suppressive effects of
      NLRP3 signaling were IL-10 dependent. Pharmacological inhibition or deletion of
      NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD complex),
      or caspase-1 protected against PDA and was associated with immunogenic
      reprogramming of innate and adaptive immunity within the TME. Similarly, transfer
      of PDA-entrained macrophages or T cells from NLRP3-/- hosts was protective. These
      data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA.

PMID- 28442556
TI  - Short course treatment for MDR TB: jumping the gun?

PMID- 28442557
TI  - High phosphate induces a pro-inflammatory response by vascular smooth muscle
      cells and modulation by vitamin D derivatives.
AB  - In chronic kidney disease patients, high phosphate (HP) levels are associated
      with cardiovascular disease, the major cause of morbidity and mortality. Since
      serum phosphate has been independently correlated with inflammation, the present
      study aimed to investigate an independent direct effect of HP as a pro
      inflammatory factor in VSMCs. A possible modulatory effect of vitamin D (VitD)
      was also investigated. The study was performed in an in vitro model of human
      aortic smooth muscle cells (HASMCs). Incubation of cells in an HP (3.3 mM) medium
      caused an increased expression of the pro-inflammatory mediators intercellular
      adhesion molecule 1 (ICAM-1), interleukins (ILs) IL-1beta, IL-6, IL-8 and tumour
      necrosis factor alpha (TNF-alpha) (not corroborated at the protein levels for
      ICAM-1), as well as an increase in reactive oxygen/nitrogen species (ROS/RNS)
      production. This was accompanied by the activation of nuclear factor kappa-light
      chain-enhancer of activated B cells (NF-kappaB) signalling as demonstrated by the
      increase in the nuclear translocation of nuclear factor kappa-light-chain
      enhancer of activated B cells protein 65 (p65-NF-kappaBeta) assessed by Western
      blotting and confocal microscopy. Since all these events were attenuated by an
      antioxidant pre-incubation with the radical scavenger Mn(III)tetrakis (4-benzoic
      acid) porphyrin (MnTBAP), it is suggested that the inflammatory response is
      upstream mediated by the ROS/RNS-induced activation of NF-kappaBeta. Addition of
      paricalcitol (PC) 3.10-8 M to cells in HP prevented the phosphate induced ROS/RNS
      increase, the activation of NF-kappaBeta and the cytokine up-regulation. A
      bimodal effect was observed, however, for different calcitriol (CTR)
      concentrations, 10-10 and 10-12 M attenuated but 10-8 M stimulated this phosphate
      induced pro-oxidative and pro-inflammatory response. Therefore, these findings
      provide novel mechanisms whereby HP may directly favour vascular dysfunctions and
      new insights into the protective effects exerted by VitD derivatives.

PMID- 28442559
TI  - Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer.
AB  - The impact of systemic 27-hydroxycholesterol (27HC) and intratumoral CYP27A1
      expression on pathobiology and clinical response to statins in breast cancer
      needs clarification. 27HC is an oxysterol produced from cholesterol by the
      monooxygenase CYP27A1, which regulates intracellular cholesterol homeostasis.
      27HC also acts as an endogenous selective estrogen receptor (ER) modulator
      capable of increasing breast cancer growth and metastasis. 27HC levels can be
      modulated by statins or direct inhibition of CYP27A1, thereby attenuating its pro
      tumorigenic activities. Herein, the effect of statins on serum 27HC and tumor
      specific CYP27A1 expression was evaluated in 42 breast cancer patients treated
      with atorvastatin within a phase II clinical trial. Further, the associations
      between CYP27A1 expression with other primary tumor pathological features and
      clinical outcomes were studied in two additional independent cohorts. Statin
      treatment effectively decreased serum 27HC and deregulated CYP27A1 expression in
      tumors. However, these changes were not associated with anti-proliferative
      responses to statin treatment. CYP27A1 was heterogeneously expressed among
      primary tumors, with high expression significantly associated with high tumor
      grade, ER negativity and basal-like subtype. High CYP27A1 expression was
      independently prognostic for longer recurrence-free and overall survival.
      Importantly, the beneficial effect of high CYP27A1 in ER-positive breast cancer
      seemed limited to women aged <=50 years. These results establish a link between
      CYP27A1 and breast cancer pathobiology and prognosis and propose that the
      efficacy of statins in reducing serum lipids does not directly translate to anti
      proliferative effects in tumors. Changes in other undetermined serum or tumor
      factors suggestively mediate the anti-proliferative effects of statins in breast
      cancer.

PMID- 28442558
TI  - Gene flow, ancient polymorphism, and ecological adaptation shape the genomic
      landscape of divergence among Darwin's finches.
AB  - Genomic comparisons of closely related species have identified "islands" of
      locally elevated sequence divergence. Genomic islands may contain functional
      variants involved in local adaptation or reproductive isolation and may therefore
      play an important role in the speciation process. However, genomic islands can
      also arise through evolutionary processes unrelated to speciation, and
      examination of their properties can illuminate how new species evolve. Here, we
      performed scans for regions of high relative divergence (FST) in 12 species pairs
      of Darwin's finches at different genetic distances. In each pair, we identify
      genomic islands that are, on average, elevated in both relative divergence (FST)
      and absolute divergence (dXY). This signal indicates that haplotypes within these
      genomic regions became isolated from each other earlier than the rest of the
      genome. Interestingly, similar numbers of genomic islands of elevated dXY are
      observed in sympatric and allopatric species pairs, suggesting that recent gene
      flow is not a major factor in their formation. We find that two of the most
      pronounced genomic islands contain the ALX1 and HMGA2 loci, which are associated
      with variation in beak shape and size, respectively, suggesting that they are
      involved in ecological adaptation. A subset of genomic island regions, including
      these loci, appears to represent anciently diverged haplotypes that evolved early
      during the radiation of Darwin's finches. Comparative genomics data indicate that
      these loci, and genomic islands in general, have exceptionally low recombination
      rates, which may play a role in their establishment.

PMID- 28442560
TI  - Obesity and menopause modify the epigenomic profile of breast cancer.
AB  - Obesity is a high risk factor for breast cancer. This relationship could be
      marked by a specific methylome. The current work was aimed to explore the impact
      of obesity and menopausal status on variation in breast cancer methylomes. Data
      from Infinium 450K array-based methylomes of 64 breast tumors were coupled with
      information on BMI and menopausal status. Additionally, DNA methylation results
      were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising
      in either pre- or postmenopausal women stratified by BMI or menopausal status
      alone were not associated with a specific DNA methylation pattern. Intriguingly,
      the DNA methylation pattern identified in association with the high-risk group
      (postmenopausal women with high BMI (>25) and premenopausal women with normal or
      low BMI < 25) exclusively characterized by hypermethylation of 1287 CpG sites as
      compared with the low-risk group. These CpG sites included the promoter region of
      fourteen protein-coding genes of which CpG methylation over the ZNF577 promoter
      region represents the top scoring associated event. In an independent cohort, the
      ZNF577 promoter methylation remained statistically significant in association
      with the high-risk group. Additionally, the impact of ZNF577 promoter methylation
      on mRNA expression levels was demonstrated in breast cancer cell lines after
      treatment with a demethylating agent (5-azacytidine). In conclusion, the
      epigenome of breast tumors is affected by a complex interaction between BMI and
      menopausal status. The ZNF577 methylation quantification is clearly relevant for
      the development of novel biomarkers of precision therapy in breast cancer.

PMID- 28442562
TI  - EBV germinates lymphoma from the germinal center in a battle with T and NK cells.

PMID- 28442561
TI  - Spread of Zika virus in the Americas.
AB  - We use a data-driven global stochastic epidemic model to analyze the spread of
      the Zika virus (ZIKV) in the Americas. The model has high spatial and temporal
      resolution and integrates real-world demographic, human mobility, socioeconomic,
      temperature, and vector density data. We estimate that the first introduction of
      ZIKV to Brazil likely occurred between August 2013 and April 2014 (90% credible
      interval). We provide simulated epidemic profiles of incident ZIKV infections for
      several countries in the Americas through February 2017. The ZIKV epidemic is
      characterized by slow growth and high spatial and seasonal heterogeneity,
      attributable to the dynamics of the mosquito vector and to the characteristics
      and mobility of the human populations. We project the expected timing and number
      of pregnancies infected with ZIKV during the first trimester and provide
      estimates of microcephaly cases assuming different levels of risk as reported in
      empirical retrospective studies. Our approach represents a modeling effort aimed
      at understanding the potential magnitude and timing of the ZIKV epidemic and it
      can be potentially used as a template for the analysis of future mosquito-borne
      epidemics.

PMID- 28442563
TI  - Crossing the arterial wall with CARS.

PMID- 28442565
TI  - Mind the magnesium, in dantrolene suppression of malignant hyperthermia.

PMID- 28442564
TI  - On the permeation of large organic cations through the pore of ATP-gated P2X
      receptors.
AB  - Pore dilation is thought to be a hallmark of purinergic P2X receptors. The most
      commonly held view of this unusual process posits that under prolonged ATP
      exposure the ion pore expands in a striking manner from an initial small-cation
      conductive state to a dilated state, which allows the passage of larger synthetic
      cations, such as N-methyl-d-glucamine (NMDG+). However, this mechanism is
      controversial, and the identity of the natural large permeating cations remains
      elusive. Here, we provide evidence that, contrary to the time-dependent pore
      dilation model, ATP binding opens an NMDG+-permeable channel within milliseconds,
      with a conductance that remains stable over time. We show that the time course of
      NMDG+ permeability superimposes that of Na+ and demonstrate that the molecular
      motions leading to the permeation of NMDG+ are very similar to those that drive
      Na+ flow. We found, however, that NMDG+ "percolates" 10 times slower than Na+ in
      the open state, likely due to a conformational and orientational selection of
      permeating molecules. We further uncover that several P2X receptors, including
      those able to desensitize, are permeable not only to NMDG+ but also to
      spermidine, a large natural cation involved in ion channel modulation, revealing
      a previously unrecognized P2X-mediated signaling. Altogether, our data do not
      support a time-dependent dilation of the pore on its own but rather reveal that
      the open pore of P2X receptors is wide enough to allow the permeation of large
      organic cations, including natural ones. This permeation mechanism has
      considerable physiological significance.

PMID- 28442566
TI  - Bayesian posteriors for arbitrarily rare events.
AB  - We study how much data a Bayesian observer needs to correctly infer the relative
      likelihoods of two events when both events are arbitrarily rare. Each period,
      either a blue die or a red die is tossed. The two dice land on side [Formula: see
      text] with unknown probabilities [Formula: see text] and [Formula: see text],
      which can be arbitrarily low. Given a data-generating process where [Formula: see
      text], we are interested in how much data are required to guarantee that with
      high probability the observer's Bayesian posterior mean for [Formula: see text]
      exceeds [Formula: see text] times that for [Formula: see text] If the prior
      densities for the two dice are positive on the interior of the parameter space
      and behave like power functions at the boundary, then for every [Formula: see
      text] there exists a finite [Formula: see text] so that the observer obtains such
      an inference after [Formula: see text] periods with probability at least
      [Formula: see text] whenever [Formula: see text] The condition on [Formula: see
      text] and [Formula: see text] is the best possible. The result can fail if one of
      the prior densities converges to zero exponentially fast at the boundary.

PMID- 28442567
TI  - Perfect chemomechanical coupling of FoF1-ATP synthase.
AB  - FoF1-ATP synthase (FoF1) couples H+ flow in Fo domain and ATP
      synthesis/hydrolysis in F1 domain through rotation of the central rotor shaft,
      and the H+/ATP ratio is crucial to understand the coupling mechanism and energy
      yield in cells. Although H+/ATP ratio of the perfectly coupling enzyme can be
      predicted from the copy number of catalytic beta subunits and that of H+ binding
      c subunits as c/beta, the actual H+/ATP ratio can vary depending on coupling
      efficiency. Here, we report actual H+/ATP ratio of thermophilic Bacillus FoF1,
      whose c/beta is 10/3. Proteoliposomes reconstituted with the FoF1 were energized
      with DeltapH and Deltapsi by the acid-base transition and by valinomycin-mediated
      diffusion potential of K+ under various [ATP]/([ADP]?[Pi]) conditions, and the
      initial rate of ATP synthesis/hydrolysis was measured. Analyses of
      thermodynamically equilibrated states, where net ATP synthesis/hydrolysis is
      zero, show linear correlation between the chemical potential of ATP
      synthesis/hydrolysis and the proton motive force, giving the slope of the linear
      function, that is, H+/ATP ratio, 3.3 +/- 0.1. This value agrees well with the
      c/beta ratio. Thus, chemomechanical coupling between Fo and F1 is perfect.

PMID- 28442568
TI  - Direct counterfactual communication via quantum Zeno effect.
AB  - Intuition from our everyday lives gives rise to the belief that information
      exchanged between remote parties is carried by physical particles. Surprisingly,
      in a recent theoretical study [Salih H, Li ZH, Al-Amri M, Zubairy MS (2013) Phys
      Rev Lett 110:170502], quantum mechanics was found to allow for communication,
      even without the actual transmission of physical particles. From the viewpoint of
      communication, this mystery stems from a (nonintuitive) fundamental concept in
      quantum mechanics-wave-particle duality. All particles can be described fully by
      wave functions. To determine whether light appears in a channel, one refers to
      the amplitude of its wave function. However, in counterfactual communication,
      information is carried by the phase part of the wave function. Using a single
      photon source, we experimentally demonstrate the counterfactual communication and
      successfully transfer a monochrome bitmap from one location to another by using a
      nested version of the quantum Zeno effect.

PMID- 28442569
TI  - Density dependence in demography and dispersal generates fluctuating invasion
      speeds.
AB  - Density dependence plays an important role in population regulation and is known
      to generate temporal fluctuations in population density. However, the ways in
      which density dependence affects spatial population processes, such as species
      invasions, are less understood. Although classical ecological theory suggests
      that invasions should advance at a constant speed, empirical work is illuminating
      the highly variable nature of biological invasions, which often exhibit
      nonconstant spreading speeds, even in simple, controlled settings. Here, we
      explore endogenous density dependence as a mechanism for inducing variability in
      biological invasions with a set of population models that incorporate density
      dependence in demographic and dispersal parameters. We show that density
      dependence in demography at low population densities-i.e., an Allee effect
      combined with spatiotemporal variability in population density behind the
      invasion front can produce fluctuations in spreading speed. The density
      fluctuations behind the front can arise from either overcompensatory population
      growth or density-dependent dispersal, both of which are common in nature. Our
      results show that simple rules can generate complex spread dynamics and highlight
      a source of variability in biological invasions that may aid in ecological
      forecasting.

PMID- 28442570
TI  - Coordination chemistry controls the thiol oxidase activity of the B12-trafficking
      protein CblC.
AB  - The cobalamin or B12 cofactor supports sulfur and one-carbon metabolism and the
      catabolism of odd-chain fatty acids, branched-chain amino acids, and cholesterol.
      CblC is a B12-processing enzyme involved in an early cytoplasmic step in the
      cofactor-trafficking pathway. It catalyzes the glutathione (GSH)-dependent
      dealkylation of alkylcobalamins and the reductive decyanation of cyanocobalamin.
      CblC from Caenorhabditis elegans (ceCblC) also exhibits a robust thiol oxidase
      activity, converting reduced GSH to oxidized GSSG with concomitant scrubbing of
      ambient dissolved O2 The mechanism of thiol oxidation catalyzed by ceCblC is not
      known. In this study, we demonstrate that novel coordination chemistry accessible
      to ceCblC-bound cobalamin supports its thiol oxidase activity via a glutathionyl
      cobalamin intermediate. Deglutathionylation of glutathionyl-cobalamin by a second
      molecule of GSH yields GSSG. The crystal structure of ceCblC provides insights
      into how architectural differences at the alpha- and beta-faces of cobalamin
      promote the thiol oxidase activity of ceCblC but mute it in wild-type human CblC.
      The R161G and R161Q mutations in human CblC unmask its latent thiol oxidase
      activity and are correlated with increased cellular oxidative stress disease. In
      summary, we have uncovered key architectural features in the cobalamin-binding
      pocket that support unusual cob(II)alamin coordination chemistry and enable the
      thiol oxidase activity of ceCblC.

PMID- 28442571
TI  - beta2-Adrenergic receptor activation mobilizes intracellular calcium via a non
      canonical cAMP-independent signaling pathway.
AB  - Beta adrenergic receptors (betaARs) are G-protein-coupled receptors essential for
      physiological responses to the hormones/neurotransmitters epinephrine and
      norepinephrine which are found in the nervous system and throughout the body.
      They are the targets of numerous widely used drugs, especially in the case of the
      most extensively studied betaAR, beta2AR, whose ligands are used for asthma and
      cardiovascular disease. betaARs signal through Galphas G-proteins and via
      activation of adenylyl cyclase and cAMP-dependent protein kinase, but some
      alternative downstream pathways have also been proposed that could be important
      for understanding normal physiological functioning of betaAR signaling and its
      disruption in disease. Using fluorescence-based Ca2+ flux assays combined with
      pharmacology and gene knock-out methods, we discovered a previously unrecognized
      endogenous pathway in HEK-293 cells whereby beta2AR activation leads to robust
      Ca2+ mobilization from intracellular stores via activation of phospholipase C and
      opening of inositol trisphosphate (InsP3) receptors. This pathway did not involve
      cAMP, Galphas, or Galphai or the participation of the other members of the
      canonical beta2AR signaling cascade and, therefore, constitutes a novel signaling
      mechanism for this receptor. This newly uncovered mechanism for Ca2+ mobilization
      by beta2AR has broad implications for adrenergic signaling, cross-talk with other
      signaling pathways, and the effects of betaAR-directed drugs.

PMID- 28442572
TI  - The phospholipase iPLA2gamma is a major mediator releasing oxidized aliphatic
      chains from cardiolipin, integrating mitochondrial bioenergetics and signaling.
AB  - Cardiolipin (CL) is a dimeric phospholipid with critical roles in mitochondrial
      bioenergetics and signaling. Recently, inhibition of the release of oxidized
      fatty acyl chains from CL by the calcium-independent phospholipase A2gamma
      (iPLA2gamma)-selective inhibitor (R)-BEL suggested that iPLA2gamma is responsible
      for the hydrolysis of oxidized CL and subsequent signaling mediated by the
      released oxidized fatty acids. However, chemical inhibition by BEL is subject to
      off-target pharmacologic effects. Accordingly, to unambiguously determine the
      role of iPLA2gamma in the hydrolysis of oxidized CL, we compared alterations in
      oxidized CLs and the release of oxidized aliphatic chains from CL in experiments
      with purified recombinant iPLA2gamma, germ-line iPLA2gamma-/- mice, cardiac
      myocyte-specific iPLA2gamma transgenic mice, and wild-type mice. Using charge
      switch high mass accuracy LC-MS/MS with selected reaction monitoring and product
      ion accurate masses, we demonstrated that iPLA2gamma is the major enzyme
      responsible for the release of oxidized aliphatic chains from CL. Our results
      also indicated that iPLA2gamma selectively hydrolyzes 9-hydroxy-octadecenoic acid
      in comparison to 13-hydroxy-octadecenoic acid from oxidized CLs. Moreover,
      oxidative stress (ADP, NADPH, and Fe3+) resulted in the robust production of
      oxidized CLs in intact mitochondria from iPLA2gamma-/- mice. In sharp contrast,
      oxidized CLs were readily hydrolyzed in mitochondria from wild-type mice during
      oxidative stress. Finally, we demonstrated that CL activates the iPLA2gamma
      mediated hydrolysis of arachidonic acid from phosphatidylcholine, thereby
      integrating the production of lipid messengers from different lipid classes in
      mitochondria. Collectively, these results demonstrate the integrated roles of CL
      and iPLA2gamma in lipid second-messenger production and mitochondrial
      bioenergetics during oxidative stress.

PMID- 28442573
TI  - Cell cycle-dependent degradation of the methyltransferase SETD3 attenuates cell
      proliferation and liver tumorigenesis.
AB  - Histone modifications, including lysine methylation, are epigenetic marks that
      influence many biological pathways. Accordingly, many methyltransferases have
      critical roles in various biological processes, and their dysregulation is often
      associated with cancer. However, the biological functions and regulation of many
      methyltransferases are unclear. Here, we report that a human homolog of the
      methyltransferase SET (SU(var), enhancer of zeste, and trithorax) domain
      containing 3 (SETD3) is cell cycle-regulated; SETD3 protein levels peaked in S
      phase and were lowest in M phase. We found that the beta-isoform of the tumor
      suppressor F-box and WD repeat domain containing 7 (FBXW7beta) specifically
      mediates SETD3 degradation. Aligning the SETD3 sequence with those of well known
      FBXW7 substrates, we identified six potential non-canonical Cdc4 phosphodegrons
      (CPDs), and one of them, CPD1, is primarily phosphorylated by the kinase glycogen
      synthase kinase 3 (GSK3beta), which is required for FBXW7beta-mediated
      recognition and degradation. Moreover, depletion or inhibition of GSK3beta or
      FBXW7beta resulted in elevated SETD3 levels. Mutations of the phosphorylated
      residues in CPD1 of SETD3 abolished the interaction between FBXW7beta and SETD3
      and prevented SETD3 degradation. Our data further indicated that SETD3 levels
      positively correlated with cell proliferation of liver cancer cells and liver
      tumorigenesis in a xenograft mouse model, and that overexpression of FBXW7beta
      counteracts the SETD3's tumorigenic role. We also show that SETD3 levels
      correlate with cancer malignancy, indicated by SETD3 levels that the 54 liver
      tumors are 2-fold higher than those in the relevant adjacent tissues.
      Collectively, these data elucidated that a GSK3beta-FBXW7beta-dependent mechanism
      controls SETD3 protein levels during the cell cycle and attenuates its oncogenic
      role in liver tumorigenesis.

PMID- 28442574
TI  - The R753Q polymorphism in Toll-like receptor 2 (TLR2) attenuates innate immune
      responses to mycobacteria and impairs MyD88 adapter recruitment to TLR2.
AB  - Toll-like receptor 2 (TLR2) plays a critical role in host defenses against
      mycobacterial infections. The R753Q TLR2 polymorphism has been associated with
      increased incidence of tuberculosis and infections with non-tuberculous
      mycobacteria in human populations, but the mechanisms by which this polymorphism
      affects TLR2 signaling are unclear. In this study, we determined the impact of
      the R753Q TLR2 polymorphism on macrophage sensing of Mycobacterium smegmatis Upon
      infection with M. smegmatis, macrophages from knock-in mice harboring R753Q TLR2
      expressed lower levels of TNF-alpha, IL-1beta, IL-6, and IL-10 compared with
      cells from WT mice, but both R753Q TLR2- and WT-derived macrophages exhibited
      comparable bacterial burdens. The decreased cytokine responses in R753Q TLR2
      expressing macrophages were accompanied by impaired phosphorylation of IL-1R
      associated kinase 1 (IRAK-1), p38, ERK1/2 MAPKs, and p65 NF-kappaB, suggesting
      that the R753Q TLR2 polymorphism alters the functions of the myeloid
      differentiation primary response protein 88 (MyD88)-IRAK-dependent signaling
      axis. Supporting this notion, HEK293 cells stably transfected with YFP-tagged
      R753Q TLR2 displayed reduced recruitment of MyD88 to TLR2, decreased NF-kappaB
      activation, and impaired IL-8 expression upon exposure to M. smegmatis
      Collectively, our results indicate that the R753Q polymorphism alters TLR2
      signaling competence, leading to impaired MyD88-TLR2 assembly, reduced
      phosphorylation of IRAK-1, diminished activation of MAPKs and NF-kappaB, and
      deficient induction of cytokines in macrophages infected with M. smegmatis.

PMID- 28442575
TI  - Structure and energetics of pairwise interactions between proteasome subunits
      RPN2, RPN13, and ubiquitin clarify a substrate recruitment mechanism.
AB  - The 26S proteasome is a large cellular assembly that mediates the selective
      degradation of proteins in the nucleus and cytosol and is an established target
      for anticancer therapeutics. Protein substrates are typically targeted to the
      proteasome through modification with a polyubiquitin chain, which can be
      recognized by several proteasome-associated ubiquitin receptors. One of these
      receptors, RPN13/ADRM1, is recruited to the proteasome through direct interaction
      with the large scaffolding protein RPN2 within the 19S regulatory particle. To
      better understand the interactions between RPN13, RPN2, and ubiquitin, we used
      human proteins to map the RPN13-binding epitope to the C-terminal 14 residues of
      RPN2, which, like ubiquitin, binds the N-terminal pleckstrin-like receptor of
      ubiquitin (PRU) domain of RPN13. We also report the crystal structures of the
      RPN13 PRU domain in complex with peptides corresponding to the RPN2 C terminus
      and ubiquitin. Through mutational analysis, we validated the RPN2-binding
      interface revealed by our structures and quantified binding interactions with
      surface plasmon resonance and fluorescence polarization. In contrast to a
      previous report, we find that RPN13 binds ubiquitin with an affinity similar to
      that of other proteasome-associated ubiquitin receptors and that RPN2, ubiquitin,
      and the deubiquitylase UCH37 bind to RPN13 with independent energetics. These
      findings provide a detailed characterization of interactions that are important
      for proteasome function, indicate ubiquitin affinities that are consistent with
      the role of RPN13 as a proteasomal ubiquitin receptor, and have major
      implications for the development of novel anticancer therapeutics.

PMID- 28442576
TI  - Determination of dendritic spine morphology by the striatin scaffold protein
      STRN4 through interaction with the phosphatase PP2A.
AB  - Dendritic spines are heterogeneous and exist with various morphologies. Altered
      spine morphology might underlie the cognitive deficits in neurodevelopmental
      disorders such as autism, but how different subtypes of dendritic spines are
      selectively maintained along development is still poorly understood. Spine
      maturation requires spontaneous activity of N-methyl-d-aspartate (NMDA) receptor
      and local dendritic protein synthesis. STRN4 (also called zinedin) belongs to the
      striatin family of scaffold proteins, and some of the potential striatin
      interacting proteins are encoded by autism risk genes. Although previous studies
      have demonstrated their localization in dendritic spines, the function of various
      striatin family members in the neuron remains unknown. Here, we demonstrate that
      Strn4 mRNA is present in neuronal dendrites, and the local expression of STRN4
      protein depends on NMDA receptor activation. Notably, STRN4 is preferentially
      expressed in mushroom spines, and STRN4 specifically maintains mushroom spines
      but not thin spines and filopodia through interaction with the phosphatase PP2A.
      Our findings have therefore unraveled the local expression of STRN4 as a novel
      mechanism for the control of dendritic spine morphology.

PMID- 28442577
TI  - Association between exposure in the cement production industry and non-malignant
      respiratory effects: a systematic review.
AB  - OBJECTIVES: Based on findings from a systematic literature search, we present and
      discuss the evidence for an association between exposure to cement dust and non
      malignant respiratory effects in cement production workers. DESIGN AND SETTING:
      Systematic literature searches (MEDLINE and Embase) were performed. Outcomes were
      restricted to respiratory symptoms, lung function indices, asthma, chronic
      bronchitis, chronic obstructive pulmonary disease, pneumoconiosis, induced sputum
      or fraction of exhaled nitric oxide (FeNO) measurements. PARTICIPANTS: The
      studies included exposed cement production workers and non-exposed or low-exposed
      referents. PRIMARY AND SECONDARY OUTCOMES: The searches yielded 594 references,
      and 26 articles were included. Cross-sectional studies show reduced lung function
      levels at or above 4.5 mg/m3 of total dust and 2.2 mg/m3 of respiratory dust. ORs
      for symptoms ranged from 1.2 to 4.8, while FEV1/FVC was 1-6% lower in exposed
      than in controls. Cohort studies reported a high yearly decline in FEV1/FVC
      ranging from 0.8% to 1.7% for exposed workers. 1 longitudinal study reported
      airflow limitation at levels of exposure comparable to ~1 mg/m3 respirable and
      3.7-5.4 mg/m3 total dust. A dose-response relationship between exposure and
      decline in lung function has only been shown in 1 cohort. 2 studies have detected
      small increases in FeNO levels during a work shift; 1 study reported signs of
      airway inflammation in induced sputum, whereas another did not detect an increase
      in hospitalisation rates. CONCLUSIONS: Lack of power, adjustment for possible
      confounders and other methodological issues are limitations of many of the
      included studies. Hence, no firm conclusions can be drawn. There are few
      longitudinal data, but recent studies report a dose-response relationship between
      cement production dust exposure and declining lung function indicating a causal
      relationship, and underlining the need to reduce exposure among workers in this
      industry.

PMID- 28442578
TI  - Multicentre, non-interventional study to assess the profile of patients with
      uncontrolled rhinitis prescribed a novel formulation of azelastine hydrochloride
      and fluticasone propionate in a single spray in routine clinical practice in the
      UK.
AB  - OBJECTIVE: The aims of this study were (1) to characterise the type of patient
      prescribed MP-AzeFlu (Dymista, a novel formulation of azelastine hydrochloride,
      fluticasone propionate and excipients in a single spray) in real life in the UK
      and physicians' reasons for prescribing it and (2) to quantify the personal and
      societal burden of allergic rhinitis (AR) in the UK prior to MP-AzeFlu
      prescription. DESIGN, SETTING AND PARTICIPANTS: This multicentre, non
      interventional study enrolled patients (n=193) with moderate-to-severe AR and
      acute symptoms who were eligible to receive treatment with MP-AzeFlu according to
      its licensed indications. Information was gathered on patient demographics, AR
      history and symptom severity, symptomatology and AR treatments in the previous
      calendar year (prior to MP-AzeFlu prescription). Physicians also recorded the
      number of previous AR visits, specific reasons for these visits and their reason
      for prescribing MP-AzeFlu. RESULTS: Most patients had seasonal AR either alone
      (10.4%) or in combination with perennial AR (35.2%), but many had AR of unknown
      origin (35.8%). Prior to MP-AzeFlu prescription, patients reported troublesome
      symptoms (78.2%) and sleep disturbance (64.8%), with congestion considered the
      most bothersome (54.4%) and ocular symptoms reported by 68.4% of patients. The
      most frequent reason for MP-AzeFlu prescription was that other therapies were not
      sufficient in the past (78.8%) or not sufficient to treat acute symptoms (16.1%).
      79.3% of patients reported using >=2 AR therapies in the past year. An average of
      1.6 (SD 1.9) doctor visits due to AR were reported prior to MP-AzeFlu
      prescription. CONCLUSIONS: In the UK, MP-AzeFlu was prescribed for individuals
      (>=12 years) with moderate/severe AR irrespective of (1) previous AR treatment
      (mono or multiple), (2) previous or likely treatment failure, (3) phenotype, (4)
      number of previous physician visits for AR and (5) for the relief of both acute
      symptoms and in anticipation of allergen exposure.

PMID- 28442579
TI  - Avoidance of reporter assay distortions from fused dual reporters.
AB  - Positioning test sequences between fused reporters permits monitoring of both
      translation levels and framing, before and after the test sequence. Many studies,
      including those on recoding such as productive ribosomal frameshifting and stop
      codon readthrough, use distinguishable luciferases or fluorescent proteins as
      reporters. Occasional distortions, due to test sequence product interference with
      the individual reporter activities or stabilities, are here shown to be avoidable
      by the introduction of tandem StopGo sequences (2A) flanking the test sequence.
      Using this new vector system (pSGDluc), we provide evidence for the use of a 3'
      stem-loop stimulator for ACP2 readthrough, but failed to detect the reported
      VEGFA readthrough.

PMID- 28442580
TI  - Ethanol Reversal of Tolerance to the Antinociceptive Effects of Oxycodone and
      Hydrocodone.
AB  - This study compared the development of tolerance to two orally bioavailable
      prescription opioids, oxycodone and hydrocodone, to that of morphine, and the
      reversal of this tolerance by ethanol. Oxycodone (s.c.) was significantly more
      potent in the mouse tail-withdrawal assay than either morphine or hydrocodone.
      Oxycodone was also significantly more potent in this assay than hydrocodone when
      administered orally. Tolerance was seen following chronic subcutaneous
      administration of each of the three drugs and by the chronic administration of
      oral oxycodone, but not following the chronic oral administration of hydrocodone.
      Ethanol (1 g/kg i.p.) significantly reversed the tolerance to the subcutaneous
      administration of each of the three opioids that developed when given 30 minutes
      prior to challenge doses. It took twice as much ethanol, when given orally, to
      reverse the tolerance to oxycodone. We investigated whether the observed
      tolerance to oxycodone and its reversal by ethanol were due to biodispositional
      changes or reflected a true neuronal tolerance. As expected, a relationship
      between brain oxycodone concentrations and activity in the tail-immersion test
      existed following administration of acute oral oxycodone. Following chronic
      treatment, brain oxycodone concentrations were significantly lower than acute
      concentrations. Oral ethanol (2 g/kg) reversed the tolerance to chronic
      oxycodone, but did not alter brain concentrations of either acute or chronic
      oxycodone. These studies show that there is a metabolic component of tolerance to
      oxycodone; however, the reversal of that tolerance by ethanol is not due to an
      alteration of the biodisposition of oxycodone, but rather is neuronal in nature.

PMID- 28442581
TI  - sigma Receptor Effects of N-Substituted Benztropine Analogs: Implications for
      Antagonism of Cocaine Self-Administration.
AB  - Several N-substituted benztropine (BZT) analogs are atypical dopamine transport
      inhibitors as they have affinity for the dopamine transporter (DAT) but have
      minimal cocaine-like pharmacologic effects and can block numerous effects of
      cocaine, including its self-administration. Among these compounds, N-methyl (AHN1
      055), N-allyl (AHN2-005), and N-butyl (JHW007) analogs of 3alpha-[bis(4'
      fluorophenyl)methoxy]-tropane were more potent in antagonizing self
      administration of cocaine and d-methamphetamine than in decreasing food
      maintained responding. The antagonism of cocaine self-administration (0.03-1.0
      mg/kg per injection) with the above BZT analogs was reproduced in the present
      study. Further, the stimulant-antagonist effects resembled previously reported
      effects of pretreatments with combinations of standard DAT inhibitors and sigma1
      receptor (sigma1R) antagonists. Therefore, the present study examined binding of
      the BZT analogs to sigmaRs, as well as their in vivo sigmaR antagonist effects.
      Each of the BZT analogs displaced radiolabeled sigmaR ligands with nanomolar
      affinity. Further, self-administration of the sigmaR agonist DTG (0.1-3.2
      mg/kg/injection) was dose dependently blocked by AHN2-005 and JHW007 but
      potentiated by AHN1-055. In contrast, none of the BZT analogs that were active
      against DTG self-administration was active against the self-administration of
      agonists at dopamine D1-like [R(+)-SKF 81297, (+/-)-SKF 82958 (0.00032-0.01 mg/kg
      per injection each)], D2-like [R(-)-NPA (0.0001-0.0032 mg/kg per injection), (-)
      quinpirole (0.0032-0.1 mg/kg per injection)], or MU-opioid (remifentanil, 0.0001
      0.0032 mg/kg per injection) receptors. The present results indicate that
      behavioral antagonist effects of the N-substituted BZT analogs are specific for
      abused drugs acting at the DAT and further suggest that sigmaR antagonism
      contributes to those actions.

PMID- 28442582
TI  - LX2761, a Sodium/Glucose Cotransporter 1 Inhibitor Restricted to the Intestine,
      Improves Glycemic Control in Mice.
AB  - LX2761 is a potent sodium/glucose cotransporter 1 inhibitor restricted to the
      intestinal lumen after oral administration. Studies presented here evaluated the
      effect of orally administered LX2761 on glycemic control in preclinical models.
      In healthy mice and rats treated with LX2761, blood glucose excursions were lower
      and plasma total glucagon-like peptide-1 (GLP-1) levels higher after an oral
      glucose challenge; these decreased glucose excursions persisted even when the
      glucose challenge occurred 15 hours after LX2761 dosing in ad lib-fed mice.
      Further, treating mice with LX2761 and the dipeptidyl-peptidase 4 inhibitor
      sitagliptin synergistically increased active GLP-1 levels, suggesting increased
      LX2761-mediated release of GLP-1 into the portal circulation. LX2761 also lowered
      postprandial glucose, fasting glucose, and hemoglobin A1C, and increased plasma
      total GLP-1, during long-term treatment of mice with either early- or late-onset
      streptozotocin-diabetes; in the late-onset cohort, LX2761 treatment improved
      survival. Mice and rats treated with LX2761 occasionally had diarrhea; this dose
      dependent side effect decreased in severity and frequency over time, and LX2761
      doses were identified that decreased postprandial glucose excursions without
      causing diarrhea. Further, the frequency of LX2761-associated diarrhea was
      greatly decreased in mice either by gradual dose escalation or by pretreatment
      with resistant starch 4, which is slowly digested to glucose in the colon, a
      process that primes the colon for glucose metabolism by selecting for glucose
      fermenting bacterial species. These data suggest that clinical trials are
      warranted to determine if LX2761 doses and dosing strategies exist that provide
      improved glycemic control combined with adequate gastrointestinal tolerability in
      people living with diabetes.

PMID- 28442583
TI  - Seletalisib: Characterization of a Novel, Potent, and Selective Inhibitor of
      PI3Kdelta.
AB  - Phosphoinositide 3-kinases (PI3K) are key signaling enzymes regulating cellular
      survival, development, and function. Expression of the PI3Kdelta isoform is
      largely restricted to leukocytes and it plays a key role in immune cell
      development and function. Seletalisib is a novel small-molecule inhibitor of
      PI3Kdelta that was evaluated in biochemical assays, cellular assays of adaptive
      and innate immunity, and an in vivo rat model of inflammation. Our findings show
      that seletalisib is a potent, ATP-competitive, and selective PI3Kdelta inhibitor
      able to block protein kinase B (AKT) phosphorylation following activation of the
      B-cell receptor in a B-cell line. Moreover, seletalisib inhibited N-formyl
      peptide-stimulated but not phorbol myristate acetate-stimulated superoxide
      release from human neutrophils, consistent with a PI3Kdelta-specific activity. No
      indications of cytotoxicity were observed in peripheral blood mononuclear cells
      (PBMCs) or other cell types treated with seletalisib. Findings from cellular
      assays of adaptive immunity demonstrated that seletalisib blocks human T-cell
      production of several cytokines from activated T-cells. Additionally, seletalisib
      inhibited B-cell proliferation and cytokine release. In human whole blood assays,
      seletalisib inhibited CD69 expression upon B-cell activation and anti-IgE
      mediated basophil degranulation. Seletalisib showed dose-dependent inhibition in
      an in vivo rat model of anti-CD3-antibody-induced interleukin 2 release.
      Collectively, these data characterize seletalisib as a selective PI3Kdelta
      inhibitor and potential therapeutic candidate for the treatment of B-cell
      malignancies and autoimmune diseases driven by dysregulated proinflammatory
      cytokine secretion.

PMID- 28442585
TI  - Next-Generation Sequencing Analysis and Algorithms for PDX and CDX Models.
AB  - Patient-derived xenograft (PDX) and circulating tumor cell-derived explant (CDX)
      models are powerful methods for the study of human disease. In cancer research,
      these methods have been applied to multiple questions, including the study of
      metastatic progression, genetic evolution, and therapeutic drug responses. As PDX
      and CDX models can recapitulate the highly heterogeneous characteristics of a
      patient tumor, as well as their response to chemotherapy, there is considerable
      interest in combining them with next-generation sequencing to monitor the
      genomic, transcriptional, and epigenetic changes that accompany oncogenesis. When
      used for this purpose, their reliability is highly dependent on being able to
      accurately distinguish between sequencing reads that originate from the host, and
      those that arise from the xenograft itself. Here, we demonstrate that failure to
      correctly identify contaminating host reads when analyzing DNA- and RNA
      sequencing (DNA-Seq and RNA-Seq) data from PDX and CDX models is a major
      confounding factor that can lead to incorrect mutation calls and a failure to
      identify canonical mutation signatures associated with tumorigenicity. In
      addition, a highly sensitive algorithm and open source software tool for
      identifying and removing contaminating host sequences is described. Importantly,
      when applied to PDX and CDX models of melanoma, these data demonstrate its
      utility as a sensitive and selective tool for the correction of PDX- and CDX
      derived whole-exome and RNA-Seq data.Implications: This study describes a
      sensitive method to identify contaminating host reads in xenograft and explant
      DNA- and RNA-Seq data and is applicable to other forms of deep sequencing. Mol
      Cancer Res; 15(8); 1012-6. (c)2017 AACR.

PMID- 28442584
TI  - Apparent CB1 Receptor Rimonabant Affinity Estimates: Combination with THC and
      Synthetic Cannabinoids in the Mouse In Vivo Triad Model.
AB  - Synthetic cannabinoids (SCs) represent an emerging class of abused drugs
      associated with psychiatric complications and other substantial health risks.
      These ligands are largely sold over the internet for human consumption,
      presumably because of their high cannabinoid 1 receptor (CB1R) affinity and their
      potency in eliciting pharmacological effects similar to Delta9
      tetrahydrocannabinol (THC), as well as circumventing laws illegalizing this
      plant. Factors potentially contributing to the increased prevalence of SC abuse
      and related hospitalizations, such as increased CB1R efficacy and non-CB1R
      targets, highlight the need for quantitative pharmacological analyses to
      determine receptor mediation of the pharmacological effects of cannabinoids.
      Accordingly, the present study used pA2 and pKB analyses for quantitative
      determination of CB1R mediation in which we utilized the CB1R-selective inverse
      agonist/antagonist rimonabant to elicit rightward shifts in the dose-response
      curves of five SCs (i.e., A-834,735D; WIN55,212-2; CP55,950; JWH-073; and
      CP47,497) and THC in producing common cannabimimetic effects (i.e., catalepsy,
      antinociception, and hypothermia). The results revealed overall similarity of pA2
      and pKB values for these compounds and suggest that CB1Rs, and not other
      pharmacological targets, largely mediated the central pharmacological effects of
      SCs. More generally, affinity estimation offers a powerful pharmacological
      approach to assess potential receptor heterogeneity subserving in vivo
      pharmacological effects of SCs.

PMID- 28442588
TI  - 2016 Year in Review: Noninvasive Ventilation.
AB  - Noninvasive ventilation (NIV) is an important modality in clinical practice and
      is extensively studied. The growth of literature related to NIV over the past 20
      years has made it difficult for clinicians to stay up to date with current best
      practice. This article will summarize some of the important NIV literature
      published in 2016 and describe any impact it may have related to the clinical use
      of NIV.

PMID- 28442586
TI  - Therapeutic Targeting of PTK7 is Cytotoxic in Atypical Teratoid Rhabdoid Tumors.
AB  - Novel discoveries involving the evaluation of potential therapeutics are based on
      newly identified molecular targets for atypical teratoid rhabdoid tumors (ATRT),
      which are the most common form of infantile brain tumors. Central nervous system
      ATRTs are rare, aggressive, and fast growing tumors of the brain and spinal cord
      and carry a very poor prognosis. Currently, the standard of care for ATRT
      patients is based on surgical resection followed by systemic chemotherapy and
      radiotherapy, which result in severe side effects. As protein tyrosine kinases
      have proven to be actionable targets that reduce tumor growth in a number of
      cancers, we examined how inhibiting tyrosine kinases affected ATRT tumor growth.
      Here, we examine the therapeutic efficacy of the broad-spectrum tyrosine kinase
      inhibitor vatalanib in the treatment of ATRT. Vatalanib significantly reduced the
      growth of ATRT tumor cell lines, both in two-dimensional cell culture and in
      three-dimensional cell culture using a spheroid model. As vatalanib had a
      remarkable effect on the growth of ATRT, we decided to use a transcriptomic
      approach to therapy by examining new actionable targets, such as tyrosine
      kinases. Next-generation RNA-sequencing and NanoString data analysis showed a
      significant increase in PTK7 RNA expression levels in ATRT tumors. Inhibition of
      PTK7 by siRNA treatment significantly decreases the viability of ATRT patient
      derived tumor cell lines.Implications: These studies provide the groundwork for
      future preclinical in vivo studies aiming to investigate the efficacy of PTK7
      inhibition on ATRT tumor growth. Mol Cancer Res; 15(8); 973-83. (c)2017 AACR.

PMID- 28442589
TI  - 2016 Year in Review: Mechanical Ventilation.
AB  - The fundamental goals of mechanical ventilation are to improve pulmonary gas
      exchange and relieve respiratory distress, thus permitting lung and airway
      healing, while at the same time lessening the risk for iatrogenic complications.
      This review will summarize some of the advances in mechanical ventilation in
      2016, with a particular focus on ventilator-associated clinical challenges and
      outcomes.

PMID- 28442590
TI  - From Here to There: Vision, Value, and the Advancement of Respiratory Care.

PMID- 28442587
TI  - Combined AURKA and H3K9 Methyltransferase Targeting Inhibits Cell Growth By
      Inducing Mitotic Catastrophe.
AB  - The current integrative pathobiologic hypothesis states that pancreatic cancer
      (PDAC) develops and progresses in response to an interaction between known
      oncogenes and downstream epigenomic regulators. Congruently, this study tests a
      new combinatorial therapy based on the inhibition of the Aurora kinase A (AURKA)
      oncogene and one of its targets, the H3K9 methylation-based epigenetic pathway.
      This therapeutic combination is effective at inhibiting the in vitro growth of
      PDAC cells both, in monolayer culture systems, and in three-dimensional spheroids
      and organoids. The combination also reduces the growth of PDAC xenografts in vivo
      Mechanistically, it was found that inhibiting methyltransferases of the H3K9
      pathway in cells, which are arrested in G2-M after targeting AURKA, decreases
      H3K9 methylation at centromeres, induces mitotic aberrations, triggers an
      aberrant mitotic check point response, and ultimately leads to mitotic
      catastrophe. Combined, these data describe for the first time a hypothesis-driven
      design of an efficient combinatorial treatment that targets a dual oncogenic
      epigenomic pathway to inhibit PDAC cell growth via a cytotoxic mechanism that
      involves perturbation of normal mitotic progression to end in mitotic
      catastrophe. Therefore, this new knowledge has significant mechanistic value as
      it relates to the development of new therapies as well as biomedical
      relevance.Implications: These results outline a model for the combined inhibition
      of a genetic-to-epigenetic pathway to inhibit cell growth and suggest an
      important and provocative consideration for harnessing the capacity of cell-cycle
      inhibitors to enhance the future use of epigenetic inhibitors. Mol Cancer Res;
      15(8); 984-97. (c)2017 AACR.

PMID- 28442591
TI  - Draining the Swamp.

PMID- 28442592
TI  - High-Flow Nasal Cannula in Neonates.

PMID- 28442593
TI  - Evidence-Based Medicine Analysis of Mechanical Insufflation-Exsufflation Devices.

PMID- 28442594
TI  - Evidence-Based Medicine Analysis of Mechanical Insufflation-Exsufflation Devices
      Reply.

PMID- 28442596
TI  - Tissue-Specific Transcriptomics Reveals an Important Role of the Unfolded Protein
      Response in Maintaining Fertility upon Heat Stress in Arabidopsis.
AB  - High temperatures have a great impact on plant reproductive development and
      subsequent fruit and seed set, but the underlying molecular mechanisms are not
      well understood. We used transcriptome profiling to investigate the effect of
      heat stress on reproductive development of Arabidopsis thaliana plants and
      observed distinct response patterns in vegetative versus reproductive tissues.
      Exposure to heat stress affected reproductive developmental programs, including
      early phases of anther/ovule development and meiosis. Also, genes participating
      in the unfolded protein response (UPR) were enriched in the reproductive tissue
      specific genes that were upregulated by heat. Moreover, we found that the UPR
      deficient bzip28 bzip60 double mutant was sensitive to heat stresses and had
      reduced silique length and fertility. Comparison of heat-responsive wild type
      versus bzip28 bzip60 plants identified 521 genes that were regulated by bZIP28
      and bZIP60 upon heat stress during reproductive stages, most of which were
      noncanonical UPR genes. Chromatin immunoprecipitation coupled with high
      throughput sequencing analyses revealed 133 likely direct targets of bZIP28 in
      Arabidopsis seedlings subjected to heat stress, including 27 genes that were also
      upregulated by heat during reproductive development. Our results provide
      important insights into heat responsiveness in Arabidopsis reproductive tissues
      and demonstrate the protective roles of the UPR for maintaining fertility upon
      heat stress.

PMID- 28442597
TI  - The Emergence, Evolution, and Diversification of the miR390-TAS3-ARF Pathway in
      Land Plants.
AB  - In plants, miR390 directs the production of tasiRNAs from TRANS-ACTING SIRNA3
      (TAS3) transcripts to regulate AUXIN RESPONSIVE FACTOR (ARF) genes, critical for
      auxin signaling; these tasiRNAs are known as tasiARFs. To understand the
      evolution of this miR390-TAS3-ARF pathway, we characterized homologs of these
      three genes from thousands of plant species, from bryophytes to angiosperms. We
      found the lower-stem region of MIR390 genes, critical for accurate DICER-LIKE1
      processing, is conserved in sequence in seed plants. We propose a model for the
      transition of functional tasiRNA sequences in TAS3 genes occurred at the
      emergence of vascular plants, in which the two miR390 target sites of TAS3 genes
      showed distinct pairing patterns. Based on the cleavability of miR390 target
      sites and the distance between target site and tasiARF, we inferred a potential
      bidirectional processing mechanism exists for some TAS3 genes. We also
      demonstrated a tight mutual selection between tasiARF and its target genes and
      that ARGONAUTE7, the partner of miR390, was specified later than other factors in
      the pathway. All these data illuminate the evolutionary path of the miR390-TAS3
      ARF pathway in land plants and demonstrate the significant variation that occurs
      in this functionally important and archetypal regulatory circuit.

PMID- 28442598
TI  - Ethylene Regulates Differential Growth via BIG ARF-GEF-Dependent Post-Golgi
      Secretory Trafficking in Arabidopsis.
AB  - During early seedling development, the shoot apical meristem is protected from
      damage as the seedling emerges from soil by the formation of apical hook. Hook
      formation requires differential growth across the epidermis below the meristem in
      the hypocotyl. The plant hormones ethylene and auxin play key roles during apical
      hook development by controlling differential growth. We provide genetic and cell
      biological evidence for the role of ADP-ribosylation factor 1 (ARF1)-GTPase and
      its effector ARF-guanine-exchange factors (GEFs) of the Brefeldin A-inhibited GEF
      (BIG) family and GNOM in ethylene- and auxin-mediated control of hook
      development. We show that ARF-GEF GNOM acts early, whereas BIG ARF-GEFs act at a
      later stage of apical hook development. We show that the localization of ARF1 and
      BIG4 at the trans-Golgi network (TGN) depends on ECHIDNA (ECH), a plant homolog
      of yeast Triacylglycerol lipase (TLG2/SYP4) interacting protein Tgl2-Vesicle
      Protein 23 (TVP23). BIGs together with ECH and ARF1 mediate the secretion of AUX1
      influx carrier to the plasma membrane from the TGN during hook development and
      defects in BIG or ARF1 result in insensitivity to ethylene. Thus, our data
      indicate a division of labor within the ARF-GEF family in mediating differential
      growth with GNOM acting during the formation phase whereas BIGs act during the
      hook maintenance phase downstream of plant hormone ethylene.

PMID- 28442599
TI  - Overcoming cisplatin resistance in osteosarcoma through the miR-199a-modulated
      inhibition of HIF-1alpha.
AB  - Dysregulation of microRNAs has been shown to contribute to multiple tumorigenic
      processes, as well as to correlate with tumor progression and prognosis. MiR-199a
      has been shown to be dysregulated in multiple tumor types. However, the
      association between miR-199a and the chemoresistance features of osteosarcoma is
      not well understood, and the target genes for miR-199a and the regulatory
      mechanisms are also unknown. In this study, we demonstrated that miR-199a is
      expressed at low levels in osteosarcoma cells and patient samples. By the
      selection and establishment of cisplatin resistant osteosarcoma cell line, we
      observed a correlation between miR-199a and cisplatin resistance in osteosarcoma
      cells: resistant cells exhibit attenuated miR-199a expressions and exogenous
      overexpression of miR-199a sensitizes osteosarcoma cells to cisplatin. Moreover,
      we identified HIF-1alpha as a direct target of miR-199a. Intriguingly, cisplatin
      resistant osteosarcoma cells display significantly elevated HIF-1alpha expression
      under hypoxia. We report here overexpression of miR-199a re-sensitizes cisplatin
      resistant cells to cisplatin through inhibition of HIF-1alpha in vitro and in
      vivo Finally, by analyzing the clinical osteosarcoma patient samples, we
      demonstrate a reverse correlation between miR-199a and HIF-1alpha mRNAs. Our
      study will provide mechanisms for the microRNAs-mediated anti-cancer therapy and
      miR-199a may be considered a promising therapeutic agent for osteosarcoma
      patients who fail to respond to conventional chemotherapy.

PMID- 28442600
TI  - Effect of rivaroxaban on preventing deep vein thrombosis in aged diabetics with
      femoral neck fractures after hip replacement.
AB  - The present study estimates the effect of rivaroxaban on preventing deep vein
      thrombosis (DVT) in aged diabetics with femoral neck fractures after hip
      replacement. Our study consisted of 236 aged diabetics with femoral neck
      fractures, which were divided into the rivaroxaban and control groups. Reaction
      time (R time), clot formation time (K time), alpha angle (alpha), maximum
      amplitude (MA), clot elasticity (G) and coagulation index (CI), prothrombin time
      (PT) and activated partial thromboplastin time (APTT) were measured. DVT was
      diagnosed by color duplex Doppler ultrasound (CDDU). The risk factors of DVT were
      analysed by logistic regression analysis. Compared with the control group, in the
      rivaroxaban group, R time and K time were extended and alpha, MA and G decreased
      1 day before operation. One day after operation, the rivaroxaban group had less
      PT and APPT and lower incidence of DVT than the control group. In the two groups,
      preoperative and postoperative PT and APPT significantly differed. Body mass
      index (BMI) >=25, abnormal coagulation indicators, use of cemented femoral hip
      prosthesis, high haemoglobin content and non-ankle pump exercise after operation
      were the risk factors for DVT. Rivaroxaban could prevent DVT in aged diabetics
      with femoral neck fractures after hip replacement.

PMID- 28442601
TI  - Crystal structure of thermostable alkylsulfatase SdsAP from Pseudomonas sp. S9.
AB  - A novel alkylsulfatase from bacterium Pseudomonas sp. S9 (SdsAP) was identified
      as a thermostable alkylsulfatases (type III), which could hydrolyze the primary
      alkyl sulfate such as sodium dodecyl sulfate (SDS). Thus, it has a potential
      application of SDS biodegradation. The crystal structure of SdsAP has been solved
      to a resolution of 1.76 A and reveals that SdsAP contains the characteristic
      metallo-beta-lactamase-like fold domain, dimerization domain, and C-terminal
      sterol carrier protein type 2 (SCP-2)-like fold domain. Kinetic characterization
      of SdsAP to SDS by isothermal titration calorimetry (ITC) and enzymatic activity
      assays of constructed mutants demonstrate that Y246 and G263 are important
      residues for its preference for the hydrolysis of 'primary alkyl' chains,
      confirming that SdsAP is a primary alkylsulfatase.

PMID- 28442602
TI  - Molecular Basis of Metabolism-Mediated Conversion of PK11195 from an Antagonist
      to an Agonist of the Constitutive Androstane Receptor.
AB  - The constitutive androstane receptor (CAR) plays an important role in xenobiotic
      metabolism, energy homeostasis, and cell proliferation. Antagonism of the CAR
      represents a key strategy for studying its function and may have potential
      clinical applications. However, specific human CAR (hCAR) antagonists are limited
      and conflicting data on the activity of these compounds have been reported. 1-(2
      chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a
      typical peripheral benzodiazepine receptor ligand, has been established as a
      potent hCAR deactivator in immortalized cells; whether it inhibits hCAR activity
      under physiologically relevant conditions remains unclear. Here, we investigated
      the effects of PK11195 on hCAR in metabolically competent human primary
      hepatocytes (HPH) and HepaRG cells. We show that although PK11195 antagonizes
      hCAR in HepG2 cells, it induces the expression of CYP2B6 and CYP3A4, targets of
      hCAR and the pregnane X receptor (PXR), in HPH, HepaRG, and PXR-knockout HepaRG
      cells. Utilizing a HPH-HepG2 coculture model, we demonstrate that inclusion of
      HPH converts PK11195 from an antagonist to an agonist of hCAR, and such
      conversion was attenuated by potent CYP3A4 inhibitor ketoconazole. Metabolically,
      we show that the N-desmethyl metabolite is responsible for PK11195-mediated hCAR
      activation by facilitating hCAR interaction with coactivators and enhancing hCAR
      nuclear translocation in HPHs. Structure-activity analysis revealed that N
      demethylation alters the interaction of PK11195 with the binding pocket of hCAR
      to favor activation. Together, these results indicate that removal of a methyl
      group switches PK11195 from a potent antagonist of hCAR to an agonist in HPH and
      highlights the importance of physiologically relevant metabolism when attempting
      to define the biologic action of small molecules.

PMID- 28442603
TI  - Aspergillus fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate
      Cell Wall Homeostasis through Modulation of Chitin Synthase Activity.
AB  - Trehalose biosynthesis is found in fungi but not humans. Proteins involved in
      trehalose biosynthesis are essential for fungal pathogen virulence in humans and
      plants through multiple mechanisms. Loss of canonical trehalose biosynthesis
      genes in the human pathogen Aspergillus fumigatus significantly alters cell wall
      structure and integrity, though the mechanistic link between these virulence
      associated pathways remains enigmatic. Here we characterize genes, called tslA
      and tslB, which encode proteins that contain domains similar to those
      corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic
      residues for phosphatase activity. Loss of tslA reduces trehalose content in both
      conidia and mycelia, impairs cell wall integrity, and significantly alters cell
      wall structure. To gain mechanistic insights into the role that TslA plays in
      cell wall homeostasis, immunoprecipitation assays coupled with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) were used to reveal a direct
      interaction between TslA and CsmA, a type V chitin synthase enzyme. TslA
      regulates not only chitin synthase activity but also CsmA sub-cellular
      localization. Loss of TslA impacts the immunopathogenesis of murine invasive
      pulmonary aspergillosis through altering cytokine production and immune cell
      recruitment. In conclusion, our data provide a novel model whereby proteins in
      the trehalose pathway play a direct role in fungal cell wall homeostasis and
      consequently impact fungus-host interactions.IMPORTANCE Human fungal infections
      are increasing globally due to HIV infections and increased use of
      immunosuppressive therapies for many diseases. Therefore, new antifungal drugs
      with reduced side effects and increased efficacy are needed to improve treatment
      outcomes. Trehalose biosynthesis exists in pathogenic fungi and is absent in
      humans. Components of the trehalose biosynthesis pathway are important for the
      virulence of human-pathogenic fungi, including Aspergillus fumigatus
      Consequently, it has been proposed that components of this pathway are potential
      targets for antifungal drug development. However, how trehalose biosynthesis
      influences the fungus-host interaction remains enigmatic. One phenotype
      associated with fungal trehalose biosynthesis mutants that remains enigmatic is
      cell wall perturbation. Here we discovered a novel moonlighting role for a
      regulatory-like subunit of the trehalose biosynthesis pathway in A. fumigatus
      that regulates cell wall homeostasis through modulation of chitin synthase
      localization and activity. As the cell wall is a current and promising
      therapeutic target for fungal infections, understanding the role of trehalose
      biosynthesis in cell wall homeostasis and virulence is expected to help define
      new therapeutic opportunities.

PMID- 28442604
TI  - Hepatitis C Virus Indirectly Disrupts DNA Damage-Induced p53 Responses by
      Activating Protein Kinase R.
AB  - Many DNA tumor viruses promote cellular transformation by inactivating the
      critically important tumor suppressor protein p53. In contrast, it is not known
      whether p53 function is disrupted by hepatitis C virus (HCV), a unique, oncogenic
      RNA virus that is the leading infectious cause of liver cancer in many regions of
      the world. Here we show that HCV-permissive, liver-derived HepG2 cells engineered
      to constitutively express microRNA-122 (HepG2/miR-122 cells) have normal p53
      mediated responses to DNA damage and that HCV replication in these cells potently
      suppresses p53 responses to etoposide, an inducer of DNA damage, or nutlin-3, an
      inhibitor of p53 degradation pathways. Upregulation of p53-dependent targets is
      consequently repressed within HCV-infected cells, with potential consequences for
      cell survival. Despite this, p53 function is not disrupted by overexpression of
      the complete HCV polyprotein, suggesting that altered p53 function may result
      from the host response to viral RNA replication intermediates. Clustered
      regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated ablation of
      double-stranded RNA (dsRNA)-activated protein kinase R (PKR) restored p53
      responses while boosting HCV replication, showing that p53 inhibition results
      directly from viral activation of PKR. The hepatocellular abundance of
      phosphorylated PKR is elevated in HCV-infected chimpanzees, suggesting that PKR
      activation and consequent p53 inhibition accompany HCV infection in vivo These
      findings reveal a feature of the host response to HCV infection that may
      contribute to hepatocellular carcinogenesis.IMPORTANCE Chronic infection with
      hepatitis C virus (HCV) is the leading cause of liver cancer in most developed
      nations. However, the mechanisms whereby HCV infection promotes carcinogenesis
      remain unclear. Here, we demonstrate that HCV infection inhibits the activation
      of p53 following DNA damage. Contrary to previous reports, HCV protein expression
      is insufficient to inhibit p53. Rather, p53 inhibition is mediated by cellular
      protein kinase R (PKR), which is activated by HCV RNA replication and
      subsequently suppresses global protein synthesis. These results redefine our
      understanding of how HCV infection influences p53 function. We speculate that
      persistent disruption of p53-mediated DNA damage responses may contribute to
      hepatocellular carcinogenesis in chronically infected individuals.

PMID- 28442605
TI  - The Toll-Like Receptor 4 Antagonist Eritoran Protects Mice from Lethal Filovirus
      Challenge.
AB  - The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa, which has seen
      intermittent reemergence since it was officially declared over in February of
      2016, has demonstrated the need for the rapid development of therapeutic
      intervention strategies. Indirect evidence has suggested that the EBOV infection
      shares several commonalities associated with the onset of bacterial sepsis,
      including the development of a "cytokine storm." Eritoran, a Toll-like receptor 4
      (TLR4) antagonist, was previously shown to result in protection of mice against
      lethal influenza virus infection. Here, we report that eritoran protects against
      the lethality caused by EBOV and the closely related Marburg virus (MARV) in
      mice. Daily administration of eritoran reduced clinical signs of the disease and,
      unexpectedly, resulted in reduced viral titers. Analysis of peripheral blood
      indicated that eritoran reduced granulocytosis despite an apparent increase in
      the percentage of activated neutrophils. Surprisingly, the increased survival
      rate and reduced viremia were not accompanied by increased CD3+ T lymphocytes, as
      lymphopenia was more pronounced in eritoran-treated mice. Overall, a global
      reduction in the levels of multiple cytokines, chemokines, and free radicals was
      detected in serum, suggesting that eritoran treatment may alleviate the severity
      of the "cytokine storm." Last, we provide compelling preliminary evidence
      suggesting that eritoran treatment may alter the kinetics of cytokine responses.
      Hence, these studies are the first to demonstrate the role of TLR4 in the
      pathogenesis of EBOV disease and indicate that eritoran is a prime candidate for
      further evaluation as a clinically viable therapeutic intervention strategy for
      EBOV and MARV infections.IMPORTANCE A hallmark of bacterial sepsis is the
      uncontrolled activation of the TLR4 pathway, which is the primary cause of the
      pathological features associated with this disease. Considering the importance of
      TLR4 signaling in bacterial sepsis and the remarkable pathological similarities
      associated with infections caused by filoviruses Ebola virus (EBOV) and Marburg
      virus (MARV), we assessed the ability of eritoran, a TLR4 antagonist, to protect
      mice against these viruses. Here, we show that eritoran effectively promotes
      survival of mice of filovirus infection, as 70% and 90% of mice receiving daily
      eritoran treatment survived lethal EBOV and MARV infections, respectively.
      Eritoran treatment resulted in a remarkable global reduction of inflammatory
      mediators, which is suggestive of the mechanism of action of this therapeutic
      treatment. These studies are the first to show the critical importance of the
      TLR4 pathway in the pathogenesis of filovirus infection and may provide a new
      avenue for therapeutic interventions.

PMID- 28442606
TI  - The EXIT Strategy: an Approach for Identifying Bacterial Proteins Exported during
      Host Infection.
AB  - Exported proteins of bacterial pathogens function both in essential physiological
      processes and in virulence. Past efforts to identify exported proteins were
      limited by the use of bacteria growing under laboratory (in vitro) conditions.
      Thus, exported proteins that are exported only or preferentially in the context
      of infection may be overlooked. To solve this problem, we developed a genome-wide
      method, named EXIT (exported in vivotechnology), to identify proteins that are
      exported by bacteria during infection and applied it to Mycobacterium
      tuberculosis during murine infection. Our studies validate the power of EXIT to
      identify proteins exported during infection on an unprecedented scale (593
      proteins) and to reveal in vivo induced exported proteins (i.e., proteins
      exported significantly more during in vivo infection than in vitro). Our EXIT
      data also provide an unmatched resource for mapping the topology of M.
      tuberculosis membrane proteins. As a new approach for identifying exported
      proteins, EXIT has potential applicability to other pathogens and experimental
      conditions.IMPORTANCE There is long-standing interest in identifying exported
      proteins of bacteria as they play critical roles in physiology and virulence and
      are commonly immunogenic antigens and targets of antibiotics. While significant
      effort has been made to identify the bacterial proteins that are exported beyond
      the cytoplasm to the membrane, cell wall, or host environment, current methods to
      identify exported proteins are limited by their use of bacteria growing under
      laboratory (in vitro) conditions. Because in vitro conditions do not mimic the
      complexity of the host environment, critical exported proteins that are
      preferentially exported in the context of infection may be overlooked. We
      developed a novel method to identify proteins that are exported by bacteria
      during host infection and applied it to identify Mycobacterium tuberculosis
      proteins exported in a mouse model of tuberculosis.

PMID- 28442608
TI  - Unexpected Relations of Historical Anthrax Strain.
AB  - In 1998, it was claimed that an 80-year-old glass tube intentionally filled with
      Bacillus anthracis and embedded in a sugar lump as a WWI biological weapon still
      contained viable spores. Today, genome sequencing of three colonies isolated in
      1998 and subjected to phylogenetic analysis surprisingly identified a well-known
      B. anthracis reference strain isolated in the United States in 1981, pointing to
      accidental laboratory contamination.IMPORTANCE Next-generation sequencing and
      subsequent phylogenetic analyses are useful and reliable tools for the
      classification of recent and historical samples. The reliability of sequences
      obtained and bioinformatic algorithms has increased in recent years, and research
      has uncovered the identity of a presumed bioweapon agent as a contaminant.

PMID- 28442607
TI  - N-Methyl-d-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by
      Zika Virus Infection.
AB  - Zika virus (ZIKV) infection is a global health emergency that causes significant
      neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d
      aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have
      exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by
      blocking NMDA overstimulation with memantine. Our results show that ZIKV actively
      replicates in primary neurons and that virus replication is directly associated
      with massive neuronal cell death. Interestingly, treatment with memantine or
      other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or
      ifenprodil, prevents neuronal death without interfering with the ability of ZIKV
      to replicate in these cells. Moreover, in vivo experiments demonstrate that
      therapeutic memantine treatment prevents the increase of intraocular pressure
      (IOP) induced by infection and massively reduces neurodegeneration and
      microgliosis in the brain of infected mice. Our results indicate that the
      blockade of NMDARs by memantine provides potent neuroprotective effects against
      ZIKV-induced neuronal damage, suggesting it could be a viable treatment for
      patients at risk for ZIKV infection-induced neurodegeneration.IMPORTANCE Zika
      virus (ZIKV) infection is a global health emergency associated with serious
      neurological complications, including microcephaly and Guillain-Barre syndrome.
      Infection of experimental animals with ZIKV causes significant neuronal damage
      and microgliosis. Treatment with drugs that block NMDARs prevented neuronal
      damage both in vitro and in vivo These results suggest that overactivation of
      NMDARs contributes significantly to the neuronal damage induced by ZIKV
      infection, and this is amenable to inhibition by drug treatment.

PMID- 28442609
TI  - Speaking up about traditional and professionalism-related patient safety threats:
      a national survey of interns and residents.
AB  - BACKGROUND: Open communication between healthcare professionals about care
      concerns, also known as 'speaking up', is essential to patient safety. OBJECTIVE:
      Compare interns' and residents' experiences, attitudes and factors associated
      with speaking up about traditional versus professionalism-related safety threats.
      DESIGN: Anonymous, cross-sectional survey. SETTING: Six US academic medical
      centres, 2013-2014. PARTICIPANTS: 1800 medical and surgical interns and residents
      (47% responded). MEASUREMENTS: Attitudes about, barriers and facilitators for,
      and self-reported experience with speaking up. Likelihood of speaking up and the
      potential for patient harm in two vignettes. Safety Attitude Questionnaire (SAQ)
      teamwork and safety scales; and Speaking Up Climate for Patient Safety (SUC-Safe)
      and Speaking Up Climate for Professionalism (SUC-Prof) scales. RESULTS:
      Respondents more commonly observed unprofessional behaviour (75%, 628/837) than
      traditional safety threats (49%, 410/837); p<0.001, but reported speaking up
      about unprofessional behaviour less commonly (46%, 287/628 vs 71%, 291/410;
      p<0.001). Respondents more commonly reported fear of conflict as a barrier to
      speaking up about unprofessional behaviour compared with traditional safety
      threats (58%, 482/837 vs 42%, 348/837; p<0.001). Respondents were also less
      likely to speak up to an attending physician in the professionalism vignette than
      the traditional safety vignette, even when they perceived high potential patient
      harm (20%, 49/251 vs 71%, 179/251; p<0.001). Positive perceptions of SAQ teamwork
      climate and SUC-Safe were independently associated with speaking up in the
      traditional safety vignette (OR 1.90, 99% CI 1.36 to 2.66 and 1.46, 1.02 to 2.09,
      respectively), while only a positive perception of SUC-Prof was associated with
      speaking up in the professionalism vignette (1.76, 1.23 to 2.50). CONCLUSIONS:
      Interns and residents commonly observed unprofessional behaviour yet were less
      likely to speak up about it compared with traditional safety threats even when
      they perceived high potential patient harm. Measuring SUC-Safe, and particularly
      SUC-Prof, may fill an existing gap in safety culture assessment.

PMID- 28442610
TI  - Photo Quiz: Overwhelming Sepsis after Dog Bite in a Splenectomized Woman.

PMID- 28442611
TI  - The Brief Case: Crusted Scabies in a Leukemic Patient following a Stay in a Long
      Term Acute Care Facility.

PMID- 28442612
TI  - seqA1 Is a Useful Target for Identification of Tsukamurella pulmonis.

PMID- 28442613
TI  - Reply to Perez del Molino Bernal and Aguero Balbin, "seqA1 Is a Useful Target for
      Identification of Tsukamurella pulmonis".

PMID- 28442614
TI  - Correction for Munson and Carroll, "What's in a Name? New Bacterial Species and
      Changes to Taxonomic Status from 2012 through 2015".

PMID- 28442615
TI  - Correction for Rosales et al., "Global Multilocus Sequence Typing Analysis of
      Mycoplasma bovis Isolates Reveals Two Main Population Clusters".

PMID- 28442616
TI  - Correction for De Groote et al., "Highly Multiplexed Proteomic Analysis of
      Quantiferon Supernatants To Identify Biomarkers of Latent Tuberculosis
      Infection".

PMID- 28442617
TI  - Closing the Brief Case: Crusted Scabies in a Leukemic Patient following a Stay in
      a Long-Term Acute Care Facility.

PMID- 28442618
TI  - Answer to May 2017 Photo Quiz.

PMID- 28442619
TI  - Initial size of unilateral pleural effusion determines impact of thoracocentesis
      on oxygenation.
AB  - BACKGROUND: There have been contradicting reports in the literature regarding the
      impact of pleural fluid aspiration on patients' oxygenation. The aim of this
      study was to assess the role of the initial size of effusion on post-drainage
      oxygenation. METHODS: We studied 122 patients, aged (mean+/-SD) 61.2+/-16.8
      years, with unilateral pleural effusion and no remarkable parenchymal lesion, by
      determining PaO2, PaCO2 and [A-a] PaO2 just before thoracocentesis (T1), 30 min
      after its completion (T2) and 48 hours after the procedure (T3). Patients were
      divided into group A (75 patients) with small and moderate sized effusions and
      group B (47 patients) with large and massive effusions. The position of the
      meniscus line on the posteroanterior film, being arbitrarily set at just above
      the upper costal margin of the sixth anterior rib, was used to divide the two
      groups. Patients were studied at rest, breathing room air in the sitting
      position. Repeated measures ANOVA (related samples) and the Friedman test when
      the normality assumption was violated were used. RESULTS: In group A, at T3,
      PaO2(mm Hg) showed a statistically significant increase versus T1 (p<0.001) and
      T2 (p=0.002), while [A-a] PaO2 displayed a statistically significant decrease
      compared with T1 (p<0.001) and T2 (p=0.001). In group B, at T2, PaO2 presented
      significant decrease versus T1 (p<0.001) and T3 (p<0.001), while [A-a] PO2 was
      found to be significantly increased compared with both T1 and T3 (p<0.001).
      CONCLUSION: Patients with smaller effusions showed a small improvement in their
      oxygenation 48 hours post-thoracocentesis (T3). Patients with larger effusions
      exhibited a transient reduction in their oxygenation immediately after fluid
      removal (T2).

PMID- 28442620
TI  - The implementation of cardiac arrest treatment recommendations in English acute
      NHS trusts: a national survey.
AB  - PURPOSE OF THE STUDY: There are approximately 35 000 in-hospital cardiac arrests
      in the UK each year. Successful resuscitation requires integration of the medical
      science, training and education of clinicians and implementation of best practice
      in the clinical setting. In 2015, the International Liaison Committee on
      Resuscitation (ILCOR) published its latest resuscitation treatment
      recommendations. It is currently unknown the extent to which these treatment
      recommendations have been successfully implemented in practice in English NHS
      acute hospital trusts. METHODS: We conducted an electronic survey of English
      acute NHS trusts to assess the implementation of key ILCOR resuscitation
      treatment recommendations in relation to in-hospital cardiac arrest practice at
      English NHS acute hospital trusts. RESULTS: Of 137 eligible trusts, 73 responded
      to the survey (response rate 53.3%). The survey identified significant variation
      in the implementation of ILCOR recommendations. In particular, the use of
      waveform capnography (n=33, 45.2%) and ultrasound (n=29, 39.7%) was often
      reported to be available only in specialist areas. Post-resuscitation debriefing
      occurs following every in-hospital cardiac arrest in few trusts (5.5%, n=4),
      despite a strong ILCOR recommendation. In contrast, participation in a range of
      quality improvement strategies such as the National Cardiac Arrest Audit (90.4%,
      n=66) and resuscitation equipment provision/audit (91.8%, n=67) were high.
      Financial restrictions were identified by 65.8% (n=48) as the main barrier to
      guideline implementation. CONCLUSION: Our survey found that ILCOR treatment
      recommendations had not been fully implemented in most English NHS acute hospital
      trusts. Further work is required to better understand barriers to implementation.

PMID- 28442622
TI  - News Feature: Is video game addiction really an addiction?

PMID- 28442626
TI  - Active life, active antitumor defense.
AB  - An active lifestyle in mice stimulates adrenergic signaling in the nervous system
      that enhances the function of antitumor natural killer cells.

PMID- 28442629
TI  - Blocking a signal to host cell histones.
AB  - A plant pathogen suppresses the host immune response by preventing histone
      acetylation.

PMID- 28442624
TI  - Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated
      genes to protect against viral infections.
AB  - Interferon (IFN)-stimulated genes (ISGs) are antiviral effectors that are induced
      by IFNs through the formation of a tripartite transcription factor ISGF3, which
      is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we
      found that IFN-independent ISG expression was detectable in immortalized cell
      lines, primary intestinal and liver organoids, and liver tissues. The
      constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U
      ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and
      STAT2. Under homeostatic conditions, STAT1, STAT2, and IRF9 were found in the
      nucleus. Analysis of a chromatin immunoprecipitation sequencing data set revealed
      that STAT1 specifically bound to the promoters of ISGs even in the absence of
      IFNs. Knockdown of STAT1, STAT2, or IRF9 by RNA interference led to the decreased
      expression of various ISGs in Huh7.5 human liver cells, which was confirmed in
      mouse embryonic fibroblasts (MEFs) from STAT1-/-, STAT2-/-, or IRF9-/- mice.
      Furthermore, decreased ISG expression was accompanied by increased replication of
      hepatitis C virus and hepatitis E virus. Conversely, simultaneous overexpression
      of all ISGF3 components, but not any single factor, induced the expression of
      ISGs and inhibited viral replication; however, no phosphorylated STAT1 and STAT2
      were detected. A phosphorylation-deficient STAT1 mutant was comparable to the
      wild-type protein in mediating the IFN-independent expression of ISGs and
      antiviral activity, suggesting that ISGF3 works in a phosphorylation-independent
      manner. These data suggest that the U-ISGF3 complex is both necessary and
      sufficient for constitutive ISG expression and antiviral immunity under
      homeostatic conditions.

PMID- 28442630
TI  - Discovering relationships between nuclear receptor signaling pathways, genes, and
      tissues in Transcriptomine.
AB  - We previously developed a web tool, Transcriptomine, to explore expression
      profiling data sets involving small-molecule or genetic manipulations of nuclear
      receptor signaling pathways. We describe advances in biocuration, query interface
      design, and data visualization that enhance the discovery of uncharacterized
      biology in these pathways using this tool. Transcriptomine currently contains
      about 45 million data points encompassing more than 2000 experiments in a
      reference library of nearly 550 data sets retrieved from public archives and
      systematically curated. To make the underlying data points more accessible to
      bench biologists, we classified experimental small molecules and gene
      manipulations into signaling pathways and experimental tissues and cell lines
      into physiological systems and organs. Incorporation of these mappings into
      Transcriptomine enables the user to readily evaluate tissue-specific regulation
      of gene expression by nuclear receptor signaling pathways. Data points from
      animal and cell model experiments and from clinical data sets elucidate the roles
      of nuclear receptor pathways in gene expression events accompanying various
      normal and pathological cellular processes. In addition, data sets targeting non
      nuclear receptor signaling pathways highlight transcriptional cross-talk between
      nuclear receptors and other signaling pathways. We demonstrate with specific
      examples how data points that exist in isolation in individual data sets validate
      each other when connected and made accessible to the user in a single interface.
      In summary, Transcriptomine allows bench biologists to routinely develop research
      hypotheses, validate experimental data, or model relationships between signaling
      pathways, genes, and tissues.

PMID- 28442631
TI  - p53 dynamics in response to DNA damage vary across cell lines and are shaped by
      efficiency of DNA repair and activity of the kinase ATM.
AB  - Cellular systems show a wide range of signaling dynamics. Many of these dynamics
      are highly stereotyped, such as oscillations at a fixed frequency. However, most
      studies looking at the role of signaling dynamics focus on one or a few cell
      lines, leaving the diversity of dynamics across tissues or cell lines a largely
      unexplored question. We focused on the dynamics of the tumor suppressor protein
      p53, which regulates cell cycle arrest and apoptosis in response to DNA damage.
      We established live-cell reporters for 12 cancer cell lines expressing wild-type
      p53 and quantified p53 dynamics in response to double-strand break-inducing DNA
      damage. In many of the tested cell lines, we found that p53 abundance oscillated
      in response to ionizing radiation or the DNA-damaging chemotherapeutic
      neocarzinostatin and that the periodicity of the oscillations was fixed. In other
      cell lines, p53 abundance dynamically changed in different ways, such as a single
      broad pulse or a continuous induction. By combining single-cell assays of p53
      signaling dynamics, small-molecule screening in live cells, and mathematical
      modeling, we identified molecules that perturbed p53 dynamics and determined that
      cell-specific variation in the efficiency of DNA repair and the activity of the
      kinase ATM (ataxia-telangiectasia mutated) controlled the signaling landscape of
      p53 dynamics. Because the dynamics of wild-type p53 varied substantially between
      cell lines, our study highlights the limitation of using one line as a model
      system and emphasizes the importance of studying the dynamics of other signaling
      pathways across different cell lines and genetic backgrounds.

PMID- 28442632
TI  - Effect of Aerobic Exercise Training on Ventilatory Efficiency and Respiratory
      Drive in Obese Subjects.
AB  - BACKGROUND: Obese patients show a decline in exercise capacity and diverse
      degrees of dyspnea in association with mechanical abnormalities, increased
      ventilatory requirements secondary to the increased metabolic load, and a greater
      work of breathing. Consequently, obese patients may be particularly predisposed
      to the development of respiratory muscle fatigue during exercise. The aim of this
      study was to assess inspiratory muscle performance during incremental exercise in
      19 obese male subjects (body mass index 41 +/- 6 kg/m2) after aerobic exercise
      training using the noninvasive, inspiratory muscle tension-time index (TT0.1).
      METHODS: Measurements performed included anthropometric parameters, lung function
      assessed by spirometry, rate of perceived breathlessness with the modified Borg
      dyspnea scale (0-10), breathing pattern, maximal exercise capacity, and
      inspiratory muscle performance with a breath-by-breath automated exercise
      metabolic system during an incremental exercise test. TT0.1 was calculated using
      the equation, TT0.1 = P0.1/PImax * TI/Ttot (where P0.1 represents mouth occlusion
      pressure, PImax is maximal inspiratory pressure, and TI/Ttot is the duty cycle).
      RESULTS: At rest, there was no statistically significant difference for
      spirometric parameters and cardiorespiratory parameters between pre- and post
      training. At maximal exercise, the minute ventilation, the rate of exchange
      ratio, the rate of perceived breathlessness, and the respiratory muscle
      performance parameters were not significantly different pre- and post-training;
      in contrast, tidal volume (P = .037, effect size = 1.51), breathing frequency (P
      = .049, effect size = 0.97), power output (P = .048, effect size = 0.79), peak
      oxygen uptake (P = .02, effect size = 0.92) were significantly higher after
      training. At comparable work load, training induces lower minute ventilation,
      mouth occlusion pressure, ratio of occlusion pressure to maximal inspiratory
      pressure, TT0.1, and rate of perceived breathlessness. CONCLUSIONS: Aerobic
      exercise at ventilatory threshold can induce significant improvement in
      respiratory muscle strength, maximal exercise capacity, and inspiratory muscle
      performance and decreased dyspnea perception in obese subjects.

PMID- 28442633
TI  - Positive End-Expiratory Pressure Effect of 3 High-Flow Nasal Cannula Devices.
AB  - BACKGROUND: High-flow nasal cannula (HFNC) is supposed to provide additional PEEP
      compared with conventional oxygen therapy. However, the exact determinants of
      this PEEP effect are unclear. We investigated the factors that might affect the
      PEEP and compared PEEP performance among 3 HFNC devices. METHODS: Three available
      HFNC devices were evaluated: the AIRVO 2 device and 2 mechanical ventilators
      (SV300 and Monnal T75). A device consisting of a test lung (5600i) and an airway
      model (AMT(IE)) was used to simulate spontaneous breathing. The flows ranged from
      0 to their maximum flow with an interval of 10 L/min. The pressures were measured
      at 4 sites (nasopharynx, supraglottis, carina, and lung) under compliances of 50
      and 100 mL/cm H2O and tidal volume of 300, 500, and 700 mL with the mouth closed
      or open. The influencing factors were determined by multiple linear regression.
      The sum of squares reduction test was used to compare working curves of PEEP
      effect among 3 devices. Pairwise comparisons were conducted by using Tukey's
      multiple comparisons test within an overlap of flow from 0 to 50 L/min. RESULTS:
      A quadratic curved relationship between PEEP and flow was observed (coefficients
      were 8.97 * 10-3 for flow and 4.79 * 10-4 for a quadratic element of flow,
      respectively) but evanished when the mouth was open. The PEEP increased along
      with lung compliance (coefficient was 2.58 * 10-3). Despite the difference in
      working curves, both the mechanical ventilators performed slightly better than
      the AIRVO 2 device at higher flows (40 and 50 L/min). CONCLUSIONS: The mouth
      status, flow, and compliance were the 3 major influencing factors of PEEP effect,
      whereas performance of the 2 mechanical ventilators was slightly superior to that
      of the AIRVO 2 device at higher flows.

PMID- 28442634
TI  - Pharmacologic targeting ERK1/2 attenuates the development and progression of
      hyperuricemic nephropathy in rats.
AB  - The pathogenesis of hyperuricemia-induced chronic kidney disease is largely
      unknown. In this study, we investigated whether extracellular signal-regulated
      kinases1/2 (ERK1/2) would contribute to the development of hyperuricemic
      nephropathy (HN). In a rat model of HN induced by feeding mixture of adenine and
      potassium oxonate, increased ERK1/2 phosphorylation and severe glomerular
      sclerosis and renal interstitial fibrosis were evident, in parallel with
      diminished levels of renal function and increased urine microalbumin excretion.
      Administration of U0126, which is a selective inhibitor of the ERK1/2 pathway,
      improved renal function, decreased urine microalbumin and inhibited activation of
      renal interstitial fibroblasts as well as accumulation of extracellular proteins.
      U0126 also inhibited hyperuricemia-induced expression of multiple profibrogenic
      cytokines/chemokines and infiltration of macrophages in the kidney. Furthermore,
      U0126 treatment suppressed xanthine oxidase, which mediates uric acid production.
      It also reduced expression of the urate anion exchanger 1, which promotes
      reabsorption of uric acid, and preserved expression of organic anion transporters
      1 and 3, which accelerate uric acid excretion in the kidney of hyperuricemic
      rats. Finally, U0126 inhibited phosphorylation of Smad3, a key mediator in
      transforming growth factor (TGF-beta) signaling. In cultured renal interstitial
      fibroblasts, inhibition of ERK1/2 activation by siRNA suppressed uric acid
      induced activation of renal interstitial fibroblasts. Collectively, pharmacologic
      targeting of ERK1/2 can alleviate HN by suppressing TGF-beta signaling, reducing
      inflammation responses, and inhibiting the molecular processes associated with
      elevation of blood uric acid levels in the body. Thus, ERK1/2 inhibition may be a
      potential approach for the prevention and treatment of hyperuricemic nephropathy.

PMID- 28442635
TI  - A novel missense mutation of Mip causes semi-dominant cataracts in the Nat mouse.
AB  - Major intrinsic protein of lens fiber (MIP) is one of the proteins essential for
      maintaining lens transparency while also contributing to dominant cataracts in
      humans. The Nodai cataract (Nat) mice harbor a spontaneous mutation in Mip and
      develop early-onset nuclear cataracts. The Nat mutation is a c.631G>A mutation
      (MipNat), resulting in a glycine-to-arginine substitution (p.Gly211Arg) in the
      sixth transmembrane domain. The MipNat/Nat homozygotes exhibit congenital
      cataracts caused by the degeneration of lens fiber cells. MIP normally localizes
      to the lens fiber cell membranes. However, the MipNat/Nat mice were found to lack
      an organelle-free zone, and the MIP was mislocalized to the nuclear membrane and
      perinuclear region. Furthermore, the MipNat/+ mice exhibited milder cataracts
      than MipNat/Nat mice due to the slight degeneration of the lens fiber cells.
      Although there were no differences in the localization of MIP to the membranes of
      lens fiber cells in MipNat/+ mice compared to that in wild-type mice, the protein
      levels of MIP were significantly reduced in the eyes. These findings suggest that
      cataractogenesis in MipNat mutants are caused by defects in MIP expression.
      Overall, the MipNat mice offer a novel model to better understand the phenotypes
      and mechanisms for the development of cataracts in patients that carry missense
      mutations in MIP.

PMID- 28442636
TI  - Gender Difference in the Prognostic Value of N-Terminal Pro-B Type Natriuretic
      Peptide in Patients With Heart Failure - A Report From the Korean Heart Failure
      Registry (KorHF).
AB  - BACKGROUND: Very little data is available to evaluate the gender-specific role of
      N-terminal pro-B type natriuretic peptide (NT-proBNP). This study was performed
      to investigate whether there is a gender difference in the prognostic value of NT
      proBNP in patients hospitalized for heart failure (HF).Methods and Results:A
      total of 2,280 patients hospitalized with HF (67.9+/-14.3 years, 50.9% women)
      from the nationwide registry database were analyzed. Composite events including
      all-cause mortality and HF readmission were assessed. During the mean follow-up
      period of 1,245+/-824 days, there were 1,067 cases of composite events (49.7%).
      NT-proBNP levels were significantly higher in patients with events than those
      without in both genders (P<0.001 for each). A higher NT-proBNP level was an
      independent predictor of events (highest vs. lowest tertile: hazard ratio [HR],
      1.74; 95% confidence interval [CI], 1.25-2.43; P=0.001) in men, even after
      controlling for potential confounders. However, NT-proBNP was not associated with
      the occurrence of composite events in women in the same multivariable analysis
      (P>0.05). CONCLUSIONS: In patients with HF, the NT-proBNP level seems to be a
      more valuable marker in the prediction of long-term mortality and HF readmission
      in men than in women.

PMID- 28442637
TI  - Different Calcification Stage in Each Cusp of a Calcified Tricuspid Aortic Valve.

PMID- 28442638
TI  - Deep sequencing of the transcriptome in the anterior pituitary of heifers before
      and after ovulation.
AB  - We aimed to determine gene expression patterns in the anterior pituitary (AP) of
      heifers before and after ovulation via deep sequencing of the transcriptome (RNA
      seq) to identify new genes and clarify important pathways. Heifers were
      slaughtered on the estrus day (pre-ovulation; n=5) or 3 days after ovulation
      (post-ovulation; n=5) for AP collection. We randomly selected 4 pre-ovulation and
      4 post-ovulation APs, and the ribosomal RNA-depleted poly (A)+RNA were prepared
      to assemble next-generation sequencing libraries. The bovine APs expressed 12,769
      annotated genes at pre- or post-ovulation. The sum of the reads per kilobase of
      exon model per million mapped reads (RPKM) values of all transcriptomes were
      599,676 +/- 38,913 and 668,209 +/- 23,690, and 32.2 +/- 2.6% and 44.0 +/- 4.4% of
      these corresponded to the AP hormones in the APs of pre- and post-ovulation
      heifers, respectively. The bovine AP showed differential expression of 396 genes
      (P<0.05) in the pre- and post-ovulation APs. The 396 genes included two G-protein
      coupled receptor (GPCR) genes (GPR61 and GPR153) and those encoding 13 binding
      proteins. The AP also expressed 259 receptor and other 364 binding proteins.
      Moreover, ingenuity pathway analysis for the 396 genes revealed (P=2.4 * 10-3) a
      canonical pathway linking GPCR to cytoskeleton reorganization, actin
      polymerization, microtubule growth, and gene expression. Thus, the present study
      clarified the novel genes found to be differentially expressed before and after
      ovulation and clarified an important pathway in the AP.

PMID- 28442639
TI  - Astaxanthin increases progesterone production in cultured bovine luteal cells.
AB  - Although astaxanthin (AST) is known to be a strong antioxidant, its effects on
      reproductive function in domestic animals have not yet been elucidated in detail.
      Therefore, we investigated the effects of AST on luteal cells, which produce
      progesterone (P4), an important hormone for maintaining pregnancy. Luteal cells
      were prepared by collagenase dispersion of the corpus luteum (CL). The addition
      of racemic AST at a low concentration (<10 nM) to cultured bovine luteal cells
      increased P4 in the culture medium (P<0.05). This effect was attributed to an
      increase in the ability of luteal cells to produce P4 (P4/cell.DNA); however, the
      level of lipid peroxide (TBARS: thiobarbituric acid reactive substances) per cell
      did not decrease with the addition of AST, whose values were similar to that with
      the addition of luteinizing hormone. When optical isomers of AST (SS and RR
      types) were added to the culture medium, respectively, SS-AST was more effective
      in increasing P4 production than RR-AST. When 1 mg/kg.body weight of SS-AST
      derived from green algae was fed to cows for 2 weeks, its concentration in blood
      plasma was 10.9 nM on average, which was sufficient to expect an in vitro effect
      on the production of P4 in cows. These results suggested the potential of SS-AST
      supplements for cows to elevate luteal function.

PMID- 28442640
TI  - Left Recumbent Position Decreases Heart Rate without Alterations in Cardiac
      Autonomic Nervous System Activity in Healthy Young Adults.
AB  - Some studies have reported that recumbent position may have advantages in
      patients with heart disease and in pregnancy. However, it remains controversial
      whether recumbent position affects autonomic nervous system activity and
      hemodynamics in healthy adults. The aim of this study was to evaluate alterations
      in heart rate variability (HRV) and hemodynamics in the supine, left recumbent
      and right recumbent positions in healthy young adults. A total of 80 participants
      aged 22.8 +/- 3.1 years were enrolled in this observational study. Fifty-eight
      volunteers (29 men and 29 women) maintained the supine position followed by the
      left and right recumbent positions, while electrocardiographic data were recorded
      for spectral analysis of HRV to assess cardiac vagal nerve and sympathetic nerve
      activities. The heart rate (HR) was significantly lower in the left recumbent
      position than in the other positions. There were no statistically significant
      differences in HRV among the three positions. Considering the possibility that
      the echographic procedure affects autonomic nervous system (ANS) activity, the
      other 22 participants (11 men and 11 women) underwent an echographic evaluation
      of hemodynamics in the heart and inferior vena cava (IVC) across the three
      positions. Although a low HR was also observed, there were no statistically
      significant differences in the IVC or the heart blood volume between the supine
      and the left recumbent positions. A postural change to the left recumbent
      position does not affect the cardiac blood circulation or ANS activity, though it
      does decrease HR in healthy young adults. This finding indicates that the lower
      HR in the left recumbent position is not attributable to the ANS activity.

PMID- 28442641
TI  - Regulation of uridine diphosphate-glucuronosyltransferase 2B15 expression during
      ovulation in the rat.
AB  - Uridine diphosphate-glucuronosyltransferase 2B15 (UGT2B15) conjugates 5alpha
      androstane-3alpha, 17beta-diol (3alpha-diol) to 3alpha-diol glucuronide (3alpha
      diol G) in steroid target tissues. The present study investigated the regulation
      of UGT2B15 expression during the ovulatory process in the rat. Real-time PCR
      analysis revealed that treatment of immature rats with equine chorionic
      gonadotropin followed by human chorionic gonadotropin transiently stimulated
      UGT2B15 gene expression in granulosa cells of preovulatory follicles within 6 h.
      The progesterone receptor antagonist RU486 suppressed the gonadotropin-induced
      UGT2B15 expression. The expression of UGT2B15 and the levels of 3alpha-diol G
      were transiently increased by luteinizing hormone (LH) treatment in cultured
      preovulatory follicles. The LH-stimulated UGT2B15 mRNA level in cultured
      preovulatory follicles was inhibited by inhibitors of adenylyl cyclase,
      phosphoinositide 3-kinase and mitogen-activated protein kinase. Furthermore, a
      vitamin D receptor agonist (calcitriol) suppressed the LH-stimulated UGT2B15
      expression in a dose-dependent manner. Taken together, these results indicate
      that gonadotropins transiently stimulate UGT2B15 expression and activity in
      preovulatory follicles, and UGT2B15 mRNA levels are regulated by the progesterone
      receptor and vitamin D receptor.

PMID- 28442642
TI  - Vaginal Delivery of Benzydamine Hydrochloride through Liposomes Dispersed in
      Mucoadhesive Gels.
AB  - Liposomal vaginal drug delivery systems are important strategy in the treatment
      of both topical and systemic diseases. The aim of this study was to develop a
      vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes
      dispersed into mucoadhesive gels. The delivery system was also designed for a
      once a day dosage and to obtain controlled release of the BNZ. For this purpose
      BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M
      and Carbopol(r) 974P, which are composed of polymers that show promising
      potential as mucoadhesive vaginal delivery systems, were developed. In addition,
      a BNZ containing liposome formulation was developed for vaginal administration.
      To improve the vaginal retention time, liposome was incorporated in HPMC K100M
      and Carbopol(r) 974P gel formulations. This system is called lipogel. The
      developed BNZ liposomes have a slightly negative zeta potential (-1.50+/-0.16
      mV), a 2.25+/-0.009 um particle size and a 34% entrapment efficiency. These gels
      and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive
      value for vaginal administration. Lipogels were found to be the best formulations
      for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion
      obtained from liposomes was in the range of 0.027+/-0.045 and 0.030+/-0.017
      mJ/cm2, while the value obtained from lipogels was between 0.176+/-0.037 and
      0.243+/-0.53 mJ/cm2. N1 and N2 lipogel formulations diffused 57 and 67% of BNZ
      respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases
      drug residence time in comparison to liposomes, could improve BNZ efficacy. In
      conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising
      alternatives to traditional dosage forms for vaginal topical therapy.

PMID- 28442643
TI  - Paradigm Shifts in Nutrition Therapy for Type 2 Diabetes.
AB  - Currently, the low-energy diet is the only recognized nutrition therapy for type
      2 diabetes in Japan. However, in recent decades, many foreign scientific
      organizations have accepted various nutritional approaches to manage diabetes,
      such as the low-carbohydrate diet, the Mediterranean diet, diet approaches to
      stop hypertension (DASH), and the vegetarian diet. Moreover, growing evidence has
      called into question classical nutritional approaches such as the low-fat diet
      for the prevention of cardiovascular disease and the low-protein diet for the
      prevention of diabetic kidney disease. Similarly, the recommended nutrition
      therapy for diabetes may change in near future. Such changes in nutrition therapy
      must be dynamic and based on not only scientific evidence but also each patient's
      narrative.

PMID- 28442644
TI  - Prediction of Both Electrical and Mechanical Reverse Remodeling on Acute
      Electrocardiogram Changes After Cardiac Resynchronization Therapy.
AB  - BACKGROUND: The development of both electrical reverse remodeling and mechanical
      reverse remodeling (ERR+MRR) after cardiac resynchronization therapy (CRT)
      implantation could reduce the incidence of lethal arrhythmia, hence the
      prediction of ERR+MRR is clinically important.Methods and Results:Eighty-three
      patients (54 male; 67+/-12 years old) with CRT >6 months were enrolled. ERR was
      defined as baseline intrinsic QRS duration (iQRSd) shortening >=10 ms in lead II
      on ECG after CRT, and MRR as improvement in LVEF >=25% on echocardiography after
      CRT. Acute ECG changes were measured by comparing the pre-implant and immediate
      post-implant ECG. Ventricular arrhythmia episodes, including ventricular
      tachycardia and ventricular fibrillation, detected by the implanted device were
      recorded. Patients were classified as ERR only (n=12), MRR only (n=23), ERR+MRR
      (n=26), or non-responder (ERR- & MRR-, n=22). On multivariate regression
      analysis, difference between baseline intrinsic QRS and paced QRS duration
      (?QRSd) >35 ms was a significant predictor of ERR+MRR (sensitivity, 68%;
      specificity, 64%; AUC, 0.7; P=0.003), and paced QTc >443 ms was a negative
      predictor of ERR+MRR (sensitivity, 78%; specificity, 60%; AUC, 0.7; P=0.002). On
      Cox proportional hazard modeling, ERR+MRR may reduce risk of ventricular
      arrhythma around 70% compared with non-responder (HR, 0.29; 95% CI: 0.13-0.65).
      CONCLUSIONS: Acute ECG changes after CRT were useful predictors of ERR+MRR.
      ERR+MRR was also a protective factor for ventricular arrhythmia.

PMID- 28442645
TI  - Iatrogenic Injury of Right Coronary Artery During Tricuspid Annuloplasty.

PMID- 28442646
TI  - Clinico-pathological findings in a striped dolphin (Stenella coeruleoalba)
      affected by rhabdomyolysis and myoglobinuric nephrosis (capture myopathy).
AB  - A striped dolphin (Stenella coeruleoalba) calf stranded alive because of a Salter
      Harris fracture type 1 of a caudal vertebra and remained in a provisional
      rehabilitation facility for 3 days where the fracture stabilization was
      attempted, but he died the day after bandaging. Serum and urine samples were
      collected during hospitalization (days 1, 2 and 3 serum and day 2 urine). Serum
      analysis showed increased urea, alanine transaminase, aspartate transaminase, and
      serum amyloid A values, while creatinine was below the lower limit. Urine
      analysis showed urinary protein-to-creatinine ratio of 5.3 with glomerular
      proteinuria. Postmortem analyses demonstrated a severe rhabdomyolysis and
      myoglobinuric nephrosis, suggestive of capture myopathy syndrome. We report, for
      the first time, the clinico-pathological changes during this condition in a
      striped dolphin.

PMID- 28442648
TI  - Preface to the Special Issue: Radiation Treatment Planning System.

PMID- 28442647
TI  - Effects of high-fat diet and fructose-rich diet on obesity, dyslipidemia and
      hyperglycemia in the WBN/Kob-Leprfa rat, a new model of type 2 diabetes mellitus.
AB  - Obesity and type 2 diabetes mellitus (T2DM) are occurring at epidemic-like rates,
      and these epidemics appear to have emerged largely from changes in daily diet. In
      the present study, we compared effects of high-fat diet (HFD) and fructose-rich
      diet (FRD) in WBN/Kob-Leprfa (WBKDF) rats that spontaneously develop obesity,
      dyslipidemia and T2DM. After a 4-week feeding of each diet, WBKDF-HFD and WBKDF
      FRD rats exhibited aggravated obesity and dyslipidemia compared with WBKDF rats
      fed standard diet (STD). In contrast, hyperglycemia developed in WBKDF-STD rats
      was significantly inhibited in WBKDF-FRD rats, but not in WBKDF-HFD rats. The
      present study demonstrated that the 4-week feeding of HFD and FRD caused diet
      induced obesity with a distinct phenotype in the glucose metabolism in WBKDF
      rats.

PMID- 28442649
TI  - The Handling of the Medical Device Program with Pharmaceutical and Medical Device
      Act.

PMID- 28442650
TI  - Evolution of Dose Calculation Algorithms for External Beam Treatment Planning.

PMID- 28442651
TI  - Basics of Monte-Carlo Simulation: Focusing on Dose-to-medium and Dose-to-water.
AB  - Treatment planning systems with highly accurate dose calculation algorithms such
      as Monte-Carlo method and linear Boltzmann transport equation are becoming
      popular thanks to a development of the computer technology. These algorithms use
      new concepts, dose-to-medium and dose-to-water. However, introducing these
      concepts can cause confusion in clinical sites. Basic knowledges about Monte
      Carlo simulation and other corresponding algorithms were explained in this
      article such as the principles, the parameters and words of caution.

PMID- 28442652
TI  - An Introduction to Optimization Theory.

PMID- 28442653
TI  - Handling Density Conversion in TPS.
AB  - Conversion from CT value to density is essential to a radiation treatment
      planning system. Generally CT value is converted to the electron density in
      photon therapy. In the energy range of therapeutic photon, interactions between
      photons and materials are dominated with Compton scattering which the cross
      section depends on the electron density. The dose distribution is obtained by
      calculating TERMA and kernel using electron density where TERMA is the energy
      transferred from primary photons and kernel is a volume considering spread
      electrons. Recently, a new method was introduced which uses the physical density.
      This method is expected to be faster and more accurate than that using the
      electron density. As for particle therapy, dose can be calculated with CT-to
      stopping power conversion since the stopping power depends on the electron
      density. CT-to-stopping power conversion table is also called as CT-to-water
      equivalent range and is an essential concept for the particle therapy.

PMID- 28442654
TI  - Utility of VMAT: Aspect of Clinical Application.

PMID- 28442655
TI  - Series: Practical Evaluation of Clinical Image Quality (4): Determination of
      Image Quality in Digital Radiography System.
AB  - Recently, for medical imaging, digital radiography systems are widely used in
      clinical practices. However, a study in the past reported that a patient
      radiation exposure level by digital radiography is in fact not lower than that by
      analog radiography system. High level of attention needs to be paid for over
      exposure when using the conventional analog radiography with a screen and a film,
      as it results in high density of the film. However, for digital radiography
      systems, since the automatic adjusting function of image density is equipped with
      them, no attention for radiation dose need to be paid. Thus technologists tend to
      be careless and results in higher chance for over-exposure. Current digital
      radiography systems are high-performance in the image properties and capable of
      patient dose reduction. Especially, the image quality of the flat panel detector
      system is recognized, higher than that of the computed radiography system by
      imaging plates, in both objective and subjective evaluations. Therefore, we
      technologists are responsible for optimizing the balance between the image
      quality of the digital radiogram and the radiation dose required for each case.
      Moreover, it is also required for us as medical technologists to make effective
      use of such evaluation result of medical images for patients.

PMID- 28442656
TI  - Series: Basic Exercises Using Excel (1).

PMID- 28442657
TI  - Structural characterization and biological activities of a novel polysaccharide
      from Phyllanthus emblica.
AB  - A novel water-soluble polysaccharide named PEPW80-1, with a molecular mass of 4.7
      kDa, was isolated from the pulp tissues of Phyllanthus emblica, and purified by
      sephadex G-100 column and sephacryl S-300 HR chromatography. The structural
      features of PEPW80-1 were investigated by a combination of acid hydrolysis,
      periodate oxidation-Smith degradation, methylation analysis, gas chromatography
      mass spectrometry, scanning electron microscope, Fourier transform infrared
      spectroscopy, and nuclear magnetic resonance spectroscopy. The results showed
      that PEPW80-1 had a specific optical rotation of [alpha]25/D = +113 degrees  (c =
      0.5 mg/mL) and its backbone composed of (1,3)-linked-beta-L-rhamnose and (1,3,6)
      linkage-beta-D-galactose, with two branch chains of (1,4)-linked-alpha-D
      galactose and (1,6)-linked-beta-D-galactose and terminated with 1-alpha-L
      arabinose. The antioxidant assays showed that PEPW80-1 possess 2,2-diphenyl-1
      picrylhydrazyl radical-scavenging activity and hydroxyl radical-scavenging
      activity, enhancing reductive power. The results of immunomodulatory assays in
      vitro showed that PEPW80-1 could promote the proliferation of mouse splenocytes.
      Those proposed that PEPW80-1 might be developed as a potential value-added
      product with the activities of immunomodulator and free-radical inhibitors.

PMID- 28442658
TI  - Predominant but Previously-overlooked Prokaryotic Drivers of Reductive Nitrogen
      Transformation in Paddy Soils, Revealed by Metatranscriptomics.
AB  - Waterlogged paddy soils possess anoxic zones in which microbes actively induce
      reductive nitrogen transformation (RNT). In the present study, a shotgun RNA
      sequencing analysis (metatranscriptomics) of paddy soil samples revealed that
      most RNT gene transcripts in paddy soils were derived from Deltaproteobacteria,
      particularly the genera Anaeromyxobacter and Geobacter. Despite the frequent
      detection of the rRNA of these microbes in paddy soils, their RNT-associated
      genes have rarely been identified in previous PCR-based studies. This
      metatranscriptomic analysis provides novel insights into the diversity of RNT
      microbes present in paddy soils and the ecological function of
      Deltaproteobacteria predominating in these soils.

PMID- 28442659
TI  - Diagnostic Accuracy of Endocardial-to-Epicardial Myocardial Blood Flow Ratio for
      the Detection of Significant Coronary Artery Disease With Dynamic Myocardial
      Perfusion Dual-Source Computed Tomography.
AB  - BACKGROUND: Previous dynamic stress computed tomography perfusion (CTP) studies
      used absolute myocardial blood flow (MBF in mL/100 g/min) as a threshold to
      discriminate flow-limiting coronary artery disease (CAD), but absolute MBF can be
      vary because of multiple factors. The aim of this study was to compare the
      diagnostic performance of absolute MBF and the transmural perfusion ratio (TPR)
      for the detection of flow-limiting CAD, and to clarify the influence of CT
      delayed enhancement (CTDE) on the diagnostic performance of CTP.Methods and
      Results:We retrospectively enrolled 51 patients who underwent dual-source CTP and
      invasive coronary angiography (ICA). TPR was defined as the endocardial MBF of a
      specific segment divided by the mean of the epicardial MBF of all segments. Flow
      limiting CAD was defined as luminal diameter stenosis >90% on ICA or a lesion
      with fractional flow reserve <=0.8. Segmental presence and absence of myocardial
      scar was determined by CTDE. The area under the receiver-operating
      characteristics curve (AUC) of TPR was significantly greater than that of MBF for
      the detection of flow-limiting CAD (0.833 vs. 0.711, P=0.0273). Myocardial DE was
      present in 27 of the 51 patients and in 34 of 143 territories. When only
      territories containing DE were considered, the AUC of TPR decreased to 0.733.
      CONCLUSIONS: TPR calculated from absolute MBF demonstrated higher diagnostic
      performance for the discrimination of flow-limiting CAD when compared with
      absolute MBF itself.

PMID- 28442660
TI  - Anatomic Feasibility of Next-Generation Stent Grafts for the Management of Type A
      Aortic Dissection in Japanese Patients.
AB  - BACKGROUND: The aims of the present study were to analyze the anatomical
      characteristics of type A aortic dissections (TAAD) in Japanese patients and
      evaluate the feasibility of 3 next-generation stent grafts dedicated to
      ascending/arch aortic lesions.Methods and Results:We analyzed 172 consecutive
      patients surgically treated for TAAD at 2 institutions between 2007 and 2015.
      Computed tomography (CT) images and operative records were used to identify the
      location of entry tear (ET). The anatomical feasibility of the Zenith Ascend,
      Zenith A-branch, and TAG Thoracic Branch Endoprosthesis (TBE) was evaluated using
      the manufacturers' instructions for use (IFU). In total, 131 patients were
      included in the final analysis. Dissection was present at the sinotubular
      junction (STJ) in 107 patients (81.7%), and the mean diameter of the STJ was
      39.4+/-6.0 mm. The ET was at the STJ (n=33), ascending aorta (n=47), aortic arch
      (n=30), and descending aorta (n=21). The mean lengths from STJ to innominate
      artery and STJ to ET were 79.5+/-11.4 mm and 57.8+/-52.1 mm, respectively. When
      we applied the IFU to each anatomical measurement, we identified 0 patients as
      candidates for Zenith Ascend, 9 (6.9%) for Zenith A-branch, and 60 (45.8%) for
      TAG TBE. CONCLUSIONS: Endovascular treatment for TAAD was not feasible for most
      of this study population, with risk of stent graft-induced new entry in 81.7% of
      patients, despite the use of next-generation stent grafts.

PMID- 28442661
TI  - LOX-1 in Ischemic Stroke.

PMID- 28442662
TI  - Possible involvement of mucosal-associated invariant T cells in the progression
      of inflammatory bowel diseases.
AB  - Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in
      anti-bacterial immunity. Recent studies have demonstrated that MAIT cells might
      be implicated in inflammatory bowel diseases (IBDs), but their precise function
      in IBD remains to be elucidated. We investigated the possible involvement of MAIT
      cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy
      specimens of the colon were collected from 25 patients with ulcerative colitis
      (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals.
      Lymphocytes were isolated from the blood and colon, and then MAIT cells were
      analyzed by flow cytometry. The frequency of MAIT cells was significantly lower
      in the blood of IBD patients compared to healthy donors and significantly higher
      in the inflamed colons compared to healthy colons (P = 0.001). Among the IBD
      patients, the frequency of MAIT cells in the blood and colon was correlated with
      disease activities. In vitro activated MAIT cells from IBD patients secreted
      significantly more tumor necrosis factor-alpha and interleukin-17 than those from
      healthy donors. These findings indicate that MAIT cells are activated in IBD
      patients, and their accumulation in the inflamed mucosa is correlated with
      disease activities.

PMID- 28442663
TI  - Histochemical assessment for osteoblastic activity coupled with dysfunctional
      osteoclasts in c-src deficient mice.
AB  - Since osteoblastic activities are believed to be coupled with osteoclasts, we
      have attempted to histologically verify which of the distinct cellular
      circumstances, the presence of osteoclasts themselves or bone resorption by
      osteoclasts, is essential for coupled osteoblastic activity, by examining c-fos-/
      or c-src-/- mice. Osteopetrotic c-fos deficient (c-fos-/-) mice have no
      osteoclasts, while c-src deficient (c-src-/-) mice, another osteopetrotic model,
      develop dysfunctional osteoclasts due to a lack of ruffled borders. c-fos-/- mice
      possessed no tartrate-resistant acid phosphatase (TRAPase)-reactive osteoclasts,
      and showed very weak tissue nonspecific alkaline phosphatase (TNALPase)-reactive
      mature osteoblasts. In contrast, c-src-/- mice had many TNALPase-positive
      osteoblasts and TRAPase-reactive osteoclasts. Interestingly, the parallel layers
      of TRAPase-reactive/osteopontin-positive cement lines were observed in the
      superficial region of c-src-/- bone matrix. This indicates the possibility that
      in c-src-/- mice, osteoblasts were activated to deposit new bone matrices on the
      surfaces that osteoclasts previously passed along, even without bone resorption.
      Transmission electron microscopy demonstrated cell-to-cell contacts between
      mature osteoblasts and neighboring ruffled border-less osteoclasts, and osteoid
      including many mineralized nodules in c-src-/- mice. Thus, it seems likely that
      osteoblastic activities would be maintained in the presence of osteoclasts, even
      if they are dysfunctional.

PMID- 28442664
TI  - Induction of neural crest cells from human dental pulp-derived induced
      pluripotent stem cells.
AB  - We previously generated induced pluripotent stem (iPS) cells from human dental
      pulp cells of deciduous teeth. Neural crest cells (NCCs) play a vital role in the
      development of the oral and maxillofacial region. Therefore, NCCs represent a
      cell source for bone, cartilage, and tooth-related tissue engineering. In this
      study, we examined whether iPS cells are capable of differentiating into NCCs
      through modification of the human embryonic stem cell protocol. First, iPS cells
      were dissociated into single cells and then reaggregated in low-cell-adhesion
      plates with neural induction medium for 8 days in suspension culture to form
      neurospheres. The neurospheres were transferred to fibronectin-coated dishes and
      formed rosette structures. The migrated cells from the rosettes abundantly
      expressed NCC markers, as evidenced by real-time polymerase chain reaction,
      immunofluorescence, and flow cytometric analysis. Furthermore, the migrated cells
      exhibited the ability to differentiate into neural crest lineage cells in vitro.
      They also exhibited tissue-forming potential in vivo, differentiating into bone
      and cartilage. Collectively, the migrated cells had similar characteristics to
      those of NCCs. These results suggest that human dental pulp cell-derived iPS
      cells are capable of differentiating into NCCs. Therefore, iPS cell-derived NCCs
      represent cell sources for bone and cartilage tissue engineering.

PMID- 28442665
TI  - The amino acid at position 624 in the glycoprotein of SFTSV (severe fever with
      thrombocytopenia virus) plays a critical role in low-pH-dependent cell fusion
      activity.
AB  - Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus
      responsible for causing an emerging zoonotic disease. We previously established
      subclones from SFTSV strain YG1 based on differences in low-pH-dependent cell
      fusion activities and found two amino acid substitutions, Y328H and R624W, in the
      envelope glycoprotein (GP) of high fusion subclones. In this study, we show that
      transiently expressed GP with the R624W mutation, but not the Y328H mutation,
      induced cell fusion under acidic conditions. GP possessing either tryptophan,
      serine, glycine or aspartic acid at position 624 induced cell fusion, whereas GP
      possessing basic amino acids such as arginine or lysine did not induce cell
      fusion. These results indicated that the amino acid at position 624 has an
      important role for inducing low-pH-dependent cell fusion.

PMID- 28442666
TI  - Role of pituitary adenylyl cyclase-activating polypeptide in intracellular
      calcium dynamics of neurons and satellite cells in rat superior cervical ganglia.
AB  - Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a bioactive peptide
      with diverse effects in the nervous system. The present study investigated
      whether stimulation of PACAP receptors (PACAPRs) induces responses in neurons and
      satellite cells of the superior cervical ganglia (SCG), with special reference to
      intracellular Ca2+ ([Ca2+]i) changes. The expression of PACAPRs in SCG was
      detected by reverse transcription-PCR. PACAP type 1 receptor (PAC1R), vasoactive
      intestinal peptide receptor type (VPAC)1R, and VPAC2R transcripts were expressed
      in SCG, with PAC1R showing the highest levels. Confocal microscopy analysis
      revealed that PACAP38 and PACAP27 induced an increase in [Ca2+]i in SCG, first in
      satellite cells and subsequently in neurons. Neither extracellular Ca2+ removal
      nor Ca2+ channel blockade affected the PACAP38-induced increase in [Ca2+]i in
      satellite cells; however, this was partly inhibited in neurons. U73122 or
      xestospongin C treatment completely and partly abrogated [Ca2+]i changes in
      satellite cells and in neurons, respectively, whereas VPAC1R and VPAC2R agonists
      increased [Ca2+]i in satellite cells only. This is the first report demonstrating
      the expression of PACAPRs specifically, VPAC1 and VPAC2 in SCG and providing
      evidence for PACAP38-induced [Ca2+]i changes in both satellite cells and neurons
      via Ca2+ mobilization.

PMID- 28442667
TI  - CHARACTERISTICS OF STRESS URINARY INCONTINENCE AFTER PELVIC ORGAN PROLAPSE
      SURGERY.
AB  - (Objective) We examined the morphology and function of lower urinary tract in
      order to know characteristics of stress urinary incontinence after pelvic organ
      prolapse (POP) surgery. (Methods) One hundred twenty-five female patients (mean
      age 64.9 years, mean parity 2.2, mean body mass index (BMI) 24.4) were performed
      anti-incontinence surgery for stress urinary incontinence. Sixty-one of 125
      patients underwent POP surgery before anti-incontinence surgery. They were
      divided into groups as follows: post-POP surgery group and non-POP surgery group.
      All patients underwent one-hour pad test, chain cystourethrography (chain CG),
      Urodynamic studies (UDS) as preoperative assessment. Midurethral sling procedure
      was performed as an anti-incontinence surgery. Preoperative assessment criteria
      and postoperative treatment results were compared between two groups. (Results)
      Post-POP surgery group showed a significantly greater amount of urinary leakage
      per 1-hour pad test than non-POP surgery group (65.2+/-74.3 g vs 14.3+/-25.2 g,
      p<0.05). The diagnosis of type III urinary stress incontinence (Blaivas'
      classification) was more frequently diagnosed in post-POP surgery group than non
      POP surgery group (50.0% vs 25.0%, p<0.05). Maximum urethral closure pressure
      (MUCP) and functional profile length (FPL) of post-POP surgery group were lower
      than those of non-POP surgery group (27.4+/-9.2 vs 35.7+/-14.7, p<0.05, 27.3+/
      4.7 vs 29.9+/-5.0, p<0.05). Postoperative treatment results of post-POP surgery
      group were worse than those of non-POP surgery group (78.7% vs 92.2%, p<0.05).
      (Conclusions) Post-POP surgery group showed more severe urinary incontinence,
      lower urinary function and lower cure rate. Therefore we should keep in mind when
      approaching urinary stress incontinence.

PMID- 28442668
TI  - EXCISION OF GIANT PELVIC LIPOSARCOMA NECESSITATING FEMORAL-FEMORAL ARTERY BYPASS
      AND GAUZE PACKING FOR ILIAC ARTERY INVOLVEMENT AND MASSIVE PRE-SACRAL BLEEDING-A
      CASE REPORT.
AB  - The patient is a 43-year-old male, presented with numbness of the left lower
      extremities. Imaging studies showed a pelvic tumor 20 cm in diameter, involving
      the left ureter, left common iliac vessels, left internal and external iliac
      vessels, and inferior mesenteric artery, which was deemed unresectable. Tumor
      biopsy confirmed liposarcoma. As chemotherapy was not effective, he was referred
      to us. Following femoral-femoral artery bypass in advance, the tumor was resected
      with the sigmoid colon, left kidney, ureter, left iliac vessels, and interior
      mesenteric artery. Removal of the tumor caused massive venous hemorrhage from the
      pre-sacral plexus, which was scarcely managed by gauze packing. Open abdominal
      management was selected to avoid abdominal compartment syndrome by severe
      intestinal edema. The packed gauze was retrieved on the fourth post-operative
      day, with laparotomy closed. The postoperative course was uneventful.

PMID- 28442669
TI  - INTRAVESICAL MIGRATION OF A HEM-O-LOK CLIP AFTER ROBOT-ASSISTED RADICAL
      PROSTATECTOMY: A CASE REPORT.
AB  - The Hem-o-lok clips (HOLC) is frequently used for hemostasis of the lateral
      pedicles in robot-assisted prostatectomy (RARP) and laparoscopic radical
      prostatectomy (LRP). We report a rare post-operative complication, the migration
      of a HOLC into the bladder leading to calculus formation after RARP. A 54 year
      old man underwent RARP with nerve- sparing procedure with HOLCs in the left
      neurovascular bundle. Three months later, he was referred to our hospital for
      pollakisuria and spontaneous hematuria. Abdominal ultrasonographic examination
      and computed tomography (CT) demonstrated a bladder stone that was 7 mm in
      diameter. On cystourethroscopy, he was noted to have a yellow-colored stone at 9
      o'clock position of vesicourethral anastomosis. A cystolithotripsy for a bladder
      stone was performed until the surface of it was broken. A HOLC with a calculus
      was revealed and retrieved by stone forceps through the urethra. Since then,
      Intravesical migration of a HOLC has not been observed.

PMID- 28442671
TI  - A CASE OF AN AROMATASE-PRODUCING SERTOLI CELL TUMOR PRESENTING WITH GYNECOMASTIA.
AB  - A 64-year-old man had complained of a left scrotal mass and gynecomastia since
      June 2012. A left testicular tumor was suspected and the patient was referred to
      our department in December 2013. He presented with bilateral gynecomastia and a
      painless left scrotal mass that was firm, smooth surfaced, and the size of large
      hen's egg. Levels of markers of testicular germ cell tumors were all within
      normal range. Endocrinological examination revealed a marked elevation in serum
      estradiol (E2) level. The patient underwent high inguinal orchiectomy in December
      2013.The pathological diagnosis was a Sertoli cell tumor of the left testis.
      Immunohistochemistry revealed the expression of aromatase synthesis; we
      speculated that this E2 production by the tumor caused the gynecomastia.Serum E2
      level normalized after the orchiectomy. Owing to the diagnosis of malignancy,
      retroperitoneal lymph node dissection was performed in January 2014. No lymph
      node metastasis was found in the specimen. The gynecomastia improved gradually,
      and the patient has been free of disease since the surgery.

PMID- 28442670
TI  - A CASE OF GROWING TERATOMA SYNDROME.
AB  - A 25-year-old man with a left testicular tumor underwent a high inguinal
      orchiectomy. Histopathological examination of the resected specimen revealed
      tumors of more than one histological type, mixed forms (seminoma, immature
      teratoma). Further evaluation revealed no metastasis (pT1N0M0S1 Stage IS).Four
      months after orchiectomy, alpha-fetoprotein (AFP) was elevated.CT scan revealed
      retroperitoneal masses of recurrent tumor. Although the AFP returned to normal
      level after four courses of BEP (bleomycin, etoposide and cisplatin), the
      retroperitoneal lymph nodes continued to grow. He underwent excision of the
      retroperitoneal lymph node dissection. Histopathological examination of the
      resected specimen revealed mature teratoma.Few reports examined about the
      development mechanism of growing teratoma syndrome (GTS). We considered that the
      development mechanism of GTS in this case is induction of differentiation. In
      this case report, we discuss the development mechanism of GTS based on
      bibliographical consideration.

PMID- 28442672
TI  - SEX REASSIGNMENT SURGERY WITH LAPAROSCOPIC SIGMOID COLON VAGINOPLASTY IN A MALE
      TO FEMALE TRANSSEXUAL: A CASE REPORT.
AB  - We herein report and discuss our first experience about a sex reassignment
      surgery (SRS) with laparoscopic sigmoid colon vaginoplasty for a 40s male to
      female gender identity disorder. SRS for this subject included bilateral
      orchiectomy, penectomy, clitoroplasty, vaginoplasty, and vulvoplasty. About 20 cm
      of the sigmoid colon was harvested laparoscopicaly for the neovagina. Total
      operating time was about 9 hours, and the estimated blood loss was 900 ml without
      transfusion. There was no trouble during the postoperative course, and a
      sufficient length of vagina has been maintained.

PMID- 28442673
TI  - THE FACTORS THAT AFFECT THE DECISION TO PERFORM LAPAROSCOPIC PARTIAL NEPHRECTOMY
      FOR SMALL RENAL TUMOR.
AB  - (Objectives) Nephron sparing surgery (NSS) is strongly recommended for patients
      with T1a renal cell carcinoma (RCC) whenever surgically feasible. However,
      partial nephrectomy, particularly laparoscopic approach, remains underutilized in
      Japan compared to laparoscopic radical nephrectomy (LRN). In this study, we
      examined the safety and efficacy of laparoscopic partial nephrectomy (LPN) for
      T1a RCC compared to LRN. We also assessed the factors that affect the decision to
      perform LPN or LRN. (Patients and methods) From March 2001 to September 2014, 112
      patients with T1a renal tumors received renal surgery at our institution. Of
      these, 100 patients (LPN: 36 patients, LRN: 64 patients) underwent laparoscopic
      surgery. Treatment outcomes including surgical and oncological outcomes among
      each approach were compared. In addition, multivariate analysis was performed to
      reveal the factors that affect the decision on surgical approach. (Results) The
      ratio of patients more than 75 years old and the RENAL nephrometry score were
      higher in LRN group than those in LPN group. Operating time was longer but renal
      function was well preserved in LPN group. Importantly, blood loss, intraoperative
      and postoperative complication rate, and oncological outcome (recurrence-free
      survival and overall survival) were similar in both groups. Multivariate analysis
      revealed that age (>=75 years old), high RENAL nephrometry score, operation
      period (before 2011), and the absence of Endoscopic Surgical Skill Qualification
      (ESSQ) in surgeon were independent predictive factors that select LRN.
      (Conclusions) Our data suggests that LPN for T1a renal tumor could be performed
      safely and the decision whether LPN or LRN were performed were associated with
      technical factors such as the presence of ESSQ or operation period, as well as
      patient's factor such as age and tumor factor such as tumor complexity.

PMID- 28442675
TI  - COMPARISON LOCALIZATION RESULTS BASED ON PROSTATE BIOPSY SPECIMENS WITH RESULTS
      BASED ON RADICAL PROSTATECTOMY SPECIMENS IN PROSTATE CANCER.
AB  - (Objective) The Clinical Practice Guidelines for Prostate Cancer (2012 Edition)
      recommend a 10- to 12-core biopsy comprising six standard cores from the apex,
      midgland, and base as well as cores from six peripheral zones (PZ) outside these
      sites. In this study, we compared localization results (mapping) based on 12-core
      prostate biopsy specimens from the six standard sites and six PZ outside these
      sites with results based on radical prostatectomy specimens. (Subjects and
      methods) Of the 208 patients with prostate cancer who underwent radical
      prostatectomy at our hospital between January 2011 and July 2014, the 139 who had
      a 12-core biopsy before surgery were included in this study. Prostate needle
      biopsies were performed transrectally and the same pathologist evaluated
      preoperative biopsy specimens and resected pathology specimens. Patient age
      ranged from 52 to 77 years (median: 68 years). Prostate-specific antigen levels
      at the time of biopsy ranged from 3.1 to 84.7 ng/ml (median: 7.3 ng/ml) and the
      weight of excised tissue ranged from 17 to 90 g (median: 37 g). The surgical
      method was laparotomy in 63 cases, laparoscopy in 12 cases, and robot-assisted in
      64 cases. The preoperative T classification was cT1c in 84 cases, cT2a in 29
      cases, cT2b in 15 cases, and cT2c in 11 cases. The preoperative Gleason score was
      3+3=6 in 36 cases, 3+4=7 in 48 cases, 4+3=7 in 33 cases, 4+4=8 in 9 cases, 4+5=9
      in 11 cases, and 5+4=9 in 2 cases. The postoperative T classification was pT2a in
      38 cases, pT2b in 12 cases, pT2c in 17 cases, pT2+in 20 cases, pT3a in 47 cases,
      and pT3b in 5 cases. The postoperative Gleason score was 3+3=6 in 19 cases, 3+4=7
      in 60 cases, 4+3=7 in 39 cases, 4+4=8 in 1 case, 4+5=9 in 14 cases, 5+4=9 in 5
      cases, and 5+5=10 in 1 case. (Results) The concordance rate for detection of
      cancer (localization) in the 12 sites of the preoperative biopsy and the same
      sites of resected specimens was 59.2% (median: 7.11/12). Furthermore, the Gleason
      score of the resected specimen was higher than the preoperative score for 79
      patients (56.8%) and 63 of the 88 patients (71.6%) whose cancer was classified as
      unilateral on the basis of the preoperative biopsy were found to have cancer on
      the other side as well when the resected specimen was examined. (Conclusion) The
      results suggest that localization is not always consistent between positive
      biopsy sites and sites in resected specimens. This indicates that when attempting
      to localize prostate cancer preoperatively, it is necessary to use other tests
      such as MRI as well.

PMID- 28442674
TI  - OUTCOMES AFTER SURGICAL TREATMENT OF UPPER TRACT UROTHELIAL CARCINOMA.
AB  - (Objectives) We retrospectively investigated the prognostic factors and the role
      of adjuvant chemotherapy against upper tract urothelial carcinoma (UTUC) after
      surgery. (Materials and methods) 343 patients of UTUC who underwent radical
      nephroureterectomy at Jikei University Hospital and affiliated institutions
      between January 2004 and February 2012 were retrospectively analyzed. A chi
      squared test was used for categorical variables. Survival probabilities after
      surgery were estimated using the Kaplan-Meier method. Multivariate Cox regression
      models addressed overall survival and cancer-specific survival after surgery.
      (Results) The 5-year overall and cancer-specific survival rates were 64.6% and
      74.6%, respectively. On multivariate analysis, higher age, male, higher pT-stage
      and lymphovascular invasion (LVI) were associated with worse overall survival and
      higher pT-stage and LVI were associated with worse cancer-specific survival. 44
      patients (G3 and >=pT3) who received cisplatin-based adjuvant chemotherapy had
      improved overall survival (P=0.044). (Conclusions) Higher pT-stage, LVI were
      important prognostic variables associated with oncologic outcomes. Cisplatin
      based adjuvant chemotherapy offered a significant benefit to overall survival in
      high risk UTUC (G3 and >=pT3), but more investigations are needed to confirm its
      utility.

PMID- 28442676
TI  - COMPARISON BETWEEN EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY AT 120 AND 60 SHOCKWAVES
      PER MINUTE FOR TREATMENT OF URINARY STONES.
AB  - (Purpose) It has recently been suggested that a slow delivery rate of shockwaves
      by extracorporeal shock wave lithotripsy (SWL) improved treatment outcomes for
      urinary stones. We retrospectively analyzed the treatment outcomes of different
      shockwave delivery rates at 120 and 60 shockwaves per minute. (Patients and
      method) A total of 88 patients were treated at a fast delivery rate of 120
      shockwaves per minute between July 2010 and April 2012, and 139 patients were
      treated at a slow delivery rate of 60 shockwaves per minute between May 2012 and
      May 2014 (n=227) using a Sonolith(r) Praktis lithotripter. The treatment outcome
      of stone-free rate (SFR) after one SWL session was assessed at four weeks.
      (Result) SWL at 60 shockwaves per minute resulted in a significantly higher SFR
      compared with SWL at 120 shockwaves per minute (39.8% and 59.0%, respectively,
      p=0.0047), particularly for upper ureter (U1) stones (53.1% and 72.0%,
      respectively, p=0.028). Multivariate analysis showed that younger age, stone
      sizes of 10 mm or less, U1 stones, and slow delivery rate were significant
      predictors of a stone-free outcome. There were fewer adverse events after the
      delivery rate of 60 shockwaves per minute (p=0.058). (Conclusion) Our study
      suggests that SWL at 60 shockwaves per minute should be recommended to
      successfully treat urinary stones using the Sonolith(r) Praktis lithotripter.

PMID- 28442677
TI  - 1,2,3-Triazolyl esterization of PAK1-blocking propolis ingredients, artepillin C
      (ARC) and caffeic acid (CA), for boosting their anti-cancer/anti-PAK1 activities
      along with cell-permeability.
AB  - Artepillin C (ARC) and caffeic acid (CA) are among the major anti-cancer
      ingredients of propolis, and block the oncogenic/melanogenic/ageing kinase PAK1.
      However, mainly due to their COOH moiety, cell-permeability of these herbal
      compounds is rather limited. Thus, in this study, in an attempt to increase their
      cell-permeability without any significant loss of their water-solubility, we have
      esterized both ARC and CA with the water-soluble 1,2,3-triazolyl alcohol through
      Click Chemistry. We found that this esterization boosts the anti-cancer activity
      of ARC and CA by 100 and over 400 folds, respectively, against the PAK-dependent
      growth of A549 lung cells, but show no effect on the PAK1-independent growth of
      B16F10 melanoma cells. Confirming this "selective" toxicity, these esters are
      still capable of blocking the kinase PAK1 strongly in cell culture (with IC50
      around 5 uM), and the anti-PAK1 activity of 15A (ARC ester) and 15C (CA ester)
      appears to be 30-fold and 140-fold higher than ARC and CA, respectively. The 15A
      and 15C are 8-fold and 70-fold more cell-permeable (through the multi-drug
      resistant cell line EMT6) than ARC and CA, respectively. These data altogether
      suggest that both 15A and 15C would be far more useful than propolis for the
      treatment of a wide variety of PAK1-dependent diseases/disorders such as cancers,
      Alzheimer's diseases (AD), hypertension, diabetes (type 2), and hyper
      pigmentation.

PMID- 28442678
TI  - Frondoside A from sea cucumber and nymphaeols from Okinawa propolis: Natural anti
      cancer agents that selectively inhibit PAK1 in vitro.
AB  - A sulfated saponin called "Frondoside A" (FRA) from sea cucumber and ingredients
      from Okinawa propolis (OP) have been previously shown to suppress the PAK1
      dependent growth of A549 lung cancer as well as pancreatic cancer cells. However,
      the precise molecular mechanism underlying their anti-cancer action still remains
      to be clarified. In this study, for the first time, we found that both FRA and OP
      directly inhibit PAK1 in vitro in a selective manner (far more effectively than
      two other oncogenic kinases, LIMK and AKT). Furthermore, at least two major anti
      cancer ingredients of OP, nymphaeols A and C, also directly inhibit PAK1 in vitro
      in a selective manner. To the best of our knowledge, FRA is the first marine
      compound that selectively inhibits PAK1. Likewise, these nymphaeols are the first
      propolis ingredients that selectively inhibit PAK1.

PMID- 28442679
TI  - CORRIGENDUM: Diabetes Trend and Impact on Risk of Cardiovascular Disease in
      Middle-Aged Japanese People.

PMID- 28442682
TI  - Erratum.

PMID- 28442683
TI  - Achievements and Limits of Current Medical Therapy of Glaucoma.
AB  - Prescribing medical therapy for the treatment of glaucoma can be a complex
      process since many parameters should be taken into consideration regarding its
      achievements and limits. Today, a variety of options, including multiple drug
      classes and multiple agents within classes, are available to the clinician, but
      caution should be given to their side effects and contraindications. Glaucoma
      patients with preexisting ocular surface disease should be treated with caution,
      and preferably with preservative-free formulations, as there is an increased risk
      for symptom deterioration. The development and use of fixed-combination therapies
      has reduced the preservative-related side effects that threaten patient adherence
      and has minimized the washout effect of multiple instillations. Adherence to
      medical treatment is not only crucial to its efficacy but also to its cost
      effectiveness. Further factors to consider are that there are patients who are
      nonresponders to treatment, and also that the target intraocular pressure (IOP)
      cannot be reached in all patients, regardless of the response to treatment. The
      progression of damage can occur even under maximum medical treatment or maximally
      tolerated medical treatment, and regardless of whether low IOP levels are
      reached. Furthermore, there is some conflict between medical treatment and
      quality of life due to long-term everyday use and to side effects of treatment.
      New molecules and new delivery systems are being investigated to open new
      horizons in glaucoma management. Although the general rule is to initiate
      glaucoma management with medical treatment, the limits of medical therapy should
      be considered to identify those patients in need of surgical management.

PMID- 28442684
TI  - Enhanced Trabeculectomy: The Moorfields Safer Surgery System.
AB  - Trabeculectomy with antifibrotic treatment is still the most popular incisional
      procedure for glaucoma filtration surgery (GFS) worldwide. The advent of
      antifibrotic agents reduced failure due to scarring but resulted in increased
      complications. Advances in trabeculectomy surgery have been driven by the need to
      minimise the risk of: (1) complications and (2) surgical failure. This chapter
      covers preoperative, intraoperative, and postoperative strategies, which improve
      the outcome of GFS. Strategies to reduce the risk of complications centre on the
      prevention of postoperative hypotony by minimising the risk of overdrainage,
      postoperative wound leaks, and poor bleb morphology. Surgical techniques to
      reduce the risk of postoperative fibrosis by the use of antifibrotic agents
      (including mitomycin C) are discussed in detail. These techniques are based on a
      combination of considerable clinical experience, observation, and laboratory
      research. The need to address pre-, intra-, and postoperative issues in each
      individual patient is emphasised. These changes are embodied in the system we
      call the "Moorfields Safer Surgery System." The use of these strategies has
      considerably reduced the incidence of major complications, including hypotony,
      cystic blebs, and endophthalmitis in practices around the world. Most of these
      techniques are simple, require minimal equipment, and can be easily mastered.
      They are associated with an improvement in overall outcome and it is hoped that
      this chapter will help the reader benefit from these advances.

PMID- 28442685
TI  - Deep Sclerectomy.
AB  - Filtering surgery evolved from the classic trabeculectomy, in which penetration
      into the anterior chamber is a necessary step, toward nonpenetrating deep
      sclerectomy. The first procedure presents several serious complications, such as
      durable hypotony, hyphema, flat anterior chamber, choroidal detachment,
      endophthalmitis, and surgery-induced cataract. To avoid such drawbacks, a novel
      nonpenetrating technique was designed to improve the predictability of the
      intraocular pressure (IOP)-lowering action, while reducing the incidence of the
      immediate postoperative complications encountered with the penetrating method.
      This surgery works by building up new outflow pathways for the drainage of the
      aqueous humor while maintaining the integrity of the anterior chamber. Deep
      sclerectomy acts at the bulk of main resistance to aqueous humor egress, located
      at the juxtacanalicular meshwork and at the inner wall of Schlemm's canal. It
      consists of dissection of these two structures while keeping a thin filtering
      membrane through which aqueous humor is drained. The membrane prevents
      overfiltration and ensures a reproducible postoperative IOP. This surgery is
      indicated for most glaucomas, with the exception of angle closure and neovascular
      cases. The procedure consists in opening the conjunctiva and Tenon's capsule and
      creating a 5 * 5-mm limbus-based superficial scleral flap. A deeper scleral flap
      measuring about 4 * 4 mm is dissected and the roof of Schlemm's canal is removed.
      A space maintainer is inserted and the flap and conjunctiva are closed. Results
      after 10 years are good, with an IOP of 12.2 +/- 4.7 mmHg and an overall success
      rate of 77.6% with few complications.

PMID- 28442686
TI  - Glaucoma Drainage Implant Surgery.
AB  - Glaucoma drainage implant (GDI) surgery represents a significant advance in the
      treatment of refractory glaucomas. Recent randomized clinical trials have
      compared the efficacy and safety of this technique to standard trabeculectomy.
      Several types of implant are currently available and differ in surface area,
      shape, composition, and the presence or absence of a flow-restricting valve. Two
      separate prospective, randomized clinical trials comparing 2 types of GDI have
      reported results after 5 years of follow-up. GDIs may be placed in the anterior
      chamber, ciliary sulcus, or pars plana. Several types of patch graft material may
      be utilized to prevent tube erosion. Potential complications of GDI surgery may
      relate to immediate or late-onset hypotony, motility disturbances, corneal
      decompensation, or tube erosion.

PMID- 28442687
TI  - Postoperative Management of Penetrating and Nonpenetrating External Filtering
      Procedures.
AB  - Correct postoperative management is fundamental to prevent and treat
      complications and to optimize the success of filtering surgery. Timely control
      visits and appropriate actions and prescriptions ensure the best outcomes, allow
      recovery from a number of untoward events, and can reestablish filtration when
      failure seems imminent. In contrast, a slack follow-up and wrong interventions or
      prescriptions can lead to the failure of any surgery, no matter how accurately it
      was carried out, sometimes jeopardizing vision and even the anatomy of the globe.
      The purpose of this review is to present a rational approach to postoperative
      follow-up and to synthetically describe how to prevent, recognize and address the
      most common complications of filtering surgery, pointing out the most common
      pitfalls in the management of the operated eye.

PMID- 28442688
TI  - Ocular Surface and External Filtration Surgery: Mutual Relationships.
AB  - There is a large body of evidence from clinical and experimental studies
      indicating that the long-term use of topical drugs may induce ocular surface
      changes, causing ocular discomfort, dry eye, conjunctival inflammation,
      subconjunctival fibrosis, corneal surface impairment, and, as a consequence of
      chronic ocular surface changes, the potential risk of failure for further
      glaucoma surgery. Subclinical inflammation has also been widely described in
      patients receiving antiglaucoma treatments for long periods of time, with
      inflammatory cell infiltration and fibroblast activation in the conjunctiva and
      subconjunctival space. Preservatives, especially benzalkonium chloride, which has
      consistently demonstrated its toxic effects in laboratory, experimental, and
      clinical studies, could induce or enhance such inflammatory changes, and has been
      recently confirmed as a direct risk factor of surgical failure. As a quaternary
      ammonium, this compound causes tear film instability, loss of goblet cells,
      conjunctival squamous metaplasia and apoptosis, disruption of the corneal
      epithelium barrier, corneal nerve impairment, chronic inflammation and potential
      damage to deeper ocular tissues. Drug-induced adverse effects are therefore far
      from restricted to only allergic reactions, but they are often very difficult to
      identify because they mostly occur in a delayed or poorly specific manner, and
      result from complex and multifactorial interactions between the drugs and the
      ocular surface. Postoperatively, the ocular surface also plays an important role,
      as the conjunctiva interacts with aqueous humor and subconjunctival fibrosis may
      block aqueous outflow and cause surgical failure. As preoperative inflammation
      underlies postoperative fibrosis and therefore surgical outcome, a better
      knowledge of ocular surface changes with appropriate evaluation and management
      should thus become a new paradigm in glaucoma care over the long term.

PMID- 28442689
TI  - Wound Healing and Glaucoma Surgery: Modulating the Scarring Process with
      Conventional Antimetabolites and New Molecules.
AB  - Subconjunctival absorption of aqueous humor is an essential part of glaucoma
      filtration surgery. Mitomycin C (MMC) and 5-fluorouracil have been used to reduce
      postoperative episcleral fibrosis and scar formation in the filtering bleb area
      for more than 2 decades. Both antimetabolites have also been frequently injected
      before needling revision of failing filtering blebs. Recently, MMC was also tried
      in tube surgery and nonpenetrating filtering surgery, but its usefulness in these
      applications has not yet been determined. The main complications and side effects
      of antimetabolite-enhanced filtration surgery comprise the development of thin
      walled cystic blebs, late bleb leaks, bleb infections, endophthalmitis, chronic
      hypotony, hypotony maculopathy and corneal epithelial toxicity. Besides MMC and 5
      fluorouracil, several other agents were proposed for decreasing episcleral
      healing after glaucoma filtering surgery. Only a few were evaluated in randomized
      clinical trials, and none became generally accepted or widely used.

PMID- 28442690
TI  - Mini Drainage Devices for Anterior and Intermediate Filtration.
AB  - Mini glaucoma devices for external filtration may be implanted with an ab externo
      procedure (Ex-PRESS and InnFocus Microshunt) or with an ab interno procedure (XEN
      Gel stent). The Ex-PRESS is an FDA-approved mini glaucoma device that has been
      developed in order to simplify anterior guarded filtering procedures, making them
      faster, safer and easier. It is positioned under a scleral flap and it is
      introduced in the anterior chamber through a needle hole, avoiding the excision
      of the corneal-scleral button and the iridectomy. Like other anterior filtering
      guarded procedures, it may be associated with releasable sutures and with an
      everting suture (the safe Ex-PRESS procedure) in order to increase safety and
      efficacy. The InnFocus Microshunt is a new ab externo filtering device currently
      under investigation; it is very easy to implant and highly promising in terms of
      safety and efficacy. The XEN Gel stent is an ab interno implanted soft, collagen
      tube that makes a permanent bypass between the anterior chamber and the
      subconjunctival space. It is a smart, quick, effective and simple procedure that
      recently gained FDA approval.

PMID- 28442691
TI  - Laser-Assisted Techniques for Penetrating and Nonpenetrating Glaucoma Surgery.
AB  - The use of lasers is slowly pervading all subspecialties of ophthalmology,
      especially glaucoma, and lasers are slowly replacing many glaucoma surgeries.
      Conventional trabeculectomy has so far remained the gold standard for glaucoma
      surgery and efforts are being made to develop a new surgical approach to overcome
      the limited success rate and safety issues of this traditional procedure. There
      is a great interest in using lasers for ab interno and ab externo penetrating and
      nonpenetrating filtering surgery. Theoretically, laser-assisted surgery offers
      the potential advantage of improved accuracy, repeatability, and safety, although
      the main drawback of using lasers for this purpose is the potential collateral
      damage induced by the scattered energy. Collateral thermal damage adjacent to the
      sclerostomy site is believed to be detrimental to the long-term success of the
      filtering procedure. Employing a laser with high water absorbance and low light
      scattering reduces the extent of collateral thermal damage and improves the long
      term surgical success. An increasing number of different radiation sources have
      been examined for penetrating and nonpenetrating glaucoma surgery with various
      success rates.

PMID- 28442692
TI  - Viscocanalostomy and Canaloplasty: ab Externo Schlemm's Canal Surgery.
AB  - Ab externo Schlemm's canal (SC) surgery (e.g., viscocanalostomy and canaloplasty)
      is a valuable alternative to glaucoma filtration surgery. It targets the
      abnormally high resistance to outflow in the trabecular meshwork (TM) and
      reestablishes the physiologic outflow system. In viscocanalostomy, viscoelastic
      substance is injected to dilate SC, which in turn leads to microdisruptions of
      the inner wall. In canaloplasty, the additional intracanalicular stent (suture or
      Stegmann Canal Expander(r)) keeps the canal patent and enhances the
      circumferential flow. A prerequisite for these procedures to work is the
      integrity of the distal outflow system, which can be evaluated by 2 clinical
      tests before surgery: provocative gonioscopy with blood reflux, and fluorescein
      channelography. Ab externo SC surgery is suitable for open-angle glaucoma, but
      also for angle closure glaucoma in combination with cataract extraction.
      Intraocular pressure reduction to the mid-teens for viscocanalostomy and to the
      lower-teens for canaloplasty can be expected. The majority of complications seen
      in filtering surgery are largely eliminated by the nonpenetrating and bleb
      independent approach. Postoperative care is minimal as no bleb management such as
      needling is required, and hypotony-related complications are largely avoided by
      the intrinsic resistance of the physiologic outflow system. With its efficacy and
      high safety profile, ab externo SC surgery will continue to play an increasing
      role and will change the current concept of glaucoma surgery towards earlier
      intervention. Surgeons will be well advised to implement these antimetabolite
      free procedures into their armamentarium to meet the expectations of the
      demanding glaucoma patient.

PMID- 28442693
TI  - Ab interno Schlemm's Canal Surgery.
AB  - In primary open-angle glaucoma, the site of greatest resistance to aqueous
      outflow is thought to be the trabecular meshwork (TM) and inner wall of Schlemm's
      canal. Augmentation of the conventional (trabecular) outflow pathway can
      facilitate physiologic outflow and subsequently lower intraocular pressure. The
      most recent approach to enhancing the conventional outflow pathway is via an
      internal approach to the TM and Schlemm's canal. Ab interno Schlemm's canal
      surgery includes 4 novel surgical approaches: (1) removal of the TM and inner
      wall of Schlemm's canal by an internal approach (ab interno trabeculectomy), (2)
      implantation of a microstent to bypass the TM, (3) disruption of the TM and inner
      wall of Schlemm's canal via an internal approach (ab interno trabeculotomy), and
      (4) dilation of Schlemm's canal via an internal approach (ab interno
      canaloplasty). The first category includes the Trabectome (Neomedix, Tustin, CA,
      USA), and Kahook Dual Blade (New World Medical, Rancho Cucamonga, CA, USA). The
      second category includes the iStent (Glaukos, Laguna Hills, CA, USA), as well as
      the investigational Hydrus Microstent implant (Ivantis, Irvine, CA, USA). The
      third category includes gonioscopic-assisted transluminal trabeculotomy
      (iSciences catheter; Ellex, Adelaide, Australia), and 360 degrees  suture
      trabeculotomy (TRAB360, Sight Sciences, Menlo Park, CA, USA). The fourth category
      includes ab interno canaloplasty or AbiC (Ellex), and Visco360 (Sight Sciences).
      In contrast to external filtration surgeries, such as trabeculectomy and aqueous
      tube shunt, these procedures are categorized as internal filtration surgeries and
      are performed from an internal approach via gonioscopic guidance. Published
      results suggest that these surgical procedures are both safe and efficacious for
      the treatment of open-angle glaucoma.

PMID- 28442695
TI  - Management of Concomitant Cataract and Glaucoma.
AB  - The coexistence of cataract and glaucoma represents a challenge for the
      ophthalmologist and the issue is still open to debate. The surgical management is
      based on both the visual field defect and the loss of visual acuity. The surgical
      options currently available are: (1) cataract extraction alone, (2) sequential
      glaucoma surgery and cataract extraction, and (3) combined surgery by 1 site or
      by 2 separate sites. Phacoemulsification alone is suggested when glaucoma can be
      controlled by medication and the visual field defect is moderate and
      nonprogressive. In case of a refractory glaucoma (3 or more types of medication
      required) with associated early-stage cataract, phacoemulsification could be
      postponed until after glaucoma surgery. The cataractogenous effect of the
      procedure should be considered in this situation. Moreover, cataract extraction
      performed after a filtering surgery may lead to a reduction of the bleb function.
      When both glaucoma and cataract are sight impairing, combined surgery is
      indicated since it allows a greater intraocular pressure decrease than
      phacoemulsification alone.

PMID- 28442694
TI  - Surgical Treatment of Angle-Closure Glaucoma.
AB  - Advances in anterior segment imaging modalities have contributed new insights
      towards a better understanding of the various mechanisms of angle-closure
      glaucoma (ACG). This development is key to good decision making when confronted
      with angle-closure patients needing appropriate therapy. Surgical management of
      ACG remains an integral part of glaucoma patient care. The distinctive anatomy of
      angle-closure eyes and the few objective lines of evidence to support the
      effectiveness of the different surgical treatment options present a challenge to
      glaucoma surgeons.

PMID- 28442696
TI  - Surgical Management of Pediatric Glaucoma.
AB  - Pediatric glaucoma surgery is challenging because of the differences in anatomy
      from the adult, differences in the behavior of the tissues of a child's
      glaucomatous eye, the variety in causes of the disease, and difficulties with
      postoperative management. Goniotomy and trabeculotomy are the preferred initial
      treatments for primary congenital glaucoma. Trabeculectomy with adjunctive
      mitomycin C is more likely to succeed in older, phakic patients, but carries the
      long-term risk of bleb-associated endophthalmitis. Glaucoma drainage devices may
      be preferred in younger children and in patients with aphakic glaucoma, but these
      devices can cause tube-related complications. Lastly, cyclodestructive procedures
      are reserved for patients in whom filtering surgery has failed, given its more
      unpredictable effects and serious complications.

PMID- 28442697
TI  - When Should We Give Up Filtration Surgery: Indications, Techniques and Results of
      Cyclodestruction.
AB  - PURPOSE: Cyclodestructive procedures are traditionally used in cases of glaucoma
      that are refractory to medical and surgical therapy. The goal of this chapter is
      to describe the indications, contraindications, techniques, and pitfalls of
      cyclodestructive procedures, including transscleral cyclophotocoagulation (TCP),
      micropulse TCP (MP-TCP), endoscopic cyclophotocoagulation (ECP), and ultrasound
      cilioplasty. METHODS: A literature search for cyclodestructive techniques was
      performed, and relevant studies were included for evaluation and review. RESULTS:
      It is encouraging that TCP seems relatively efficacious even for patients who
      have been refractory to other treatments, depending on the energy setting, follow
      up period, and definition of success. Repeated TCP is often required. TCP was
      more often used in eyes with limited visual potential caused by severe forms of
      glaucoma than in eyes with good visual potential. Serious complications were
      significant vision loss, inflammation, hypotony, and phthisis. ECP came later
      into clinical use for the treatment of refractory glaucoma. ECP is able to
      specifically target the ciliary epithelium under direct viewing as compared to
      TCP, which is an indirect cyclodestructive procedure. In the literature, it has
      been demonstrated that ECP has overall good success with relatively low
      complication rates when used for adult forms of glaucoma. A new technology using
      MP-TCP is a promising alternative to conventional cyclophotocoagulation. Early
      evidence shows that MP-TCP has clinical utility and a good safety profile.
      Ultrasound cilioplasty is a possible alternative to laser cyclodestruction that
      is already being commercialized and is currently under investigation.
      CONCLUSIONS: Both TCP and ECP are effective cyclodestructive procedures and
      alternatives for the treatment of glaucoma refractory to medical and surgical
      therapy, though potential for serious complications exists. TCP, ECP, and
      ultrasound cilioplasty are being used increasingly as the primary surgery for
      various kinds and stages of glaucoma.

PMID- 28442699
TI  - Rapid fecal calprotectin test for prediction of mucosal inflammation in
      ulcerative colitis and Crohn disease: a prospective cohort study.
AB  - INTRODUCTION Fecal calprotectin (FC) is a well-established biomarker of
      intestinal inflammation in Crohn disease (CD) and ulcerative colitis (UC).
      However, standard laboratory methods are time-consuming and not always useful in
      clinical practice. OBJECTIVES We analyzed the efficacy of a rapid bedside FC test
      to detect disease flares in a hospital setting. We also assessed the influence of
      disease location on the diagnostic accuracy of FC.  PATIENTS AND METHODS This
      prospective study included 140 patients (46 with UC; 94 with CD). FC was measured
      by an enzyme-linked immunosorbent assay (ELISA) and by the rapid Quantum Blue(r)
      test. Endoscopic activity was assessed using the Mayo endoscopic subscore or the
      Simple Endoscopic Score for Crohn's Disease (SES-CD).  RESULTS FC levels highly
      correlated with endoscopic activity in CD (area under the receiver operating
      characteristic curve [AUC], 0.83) and UC (AUC, 0.80), with the cut-off values of
      238.5 MUg/g and 499 MUg/g, respectively. FC levels increased dynamically even
      with early signs of inflammation both in CD (SES-CD, 4-10 vs 0 points: 252 vs
      100.0 MUg/g; P = 0.02) and UC (Mayo subscore, 1 vs 0 points: 323.3 vs 100.0
      MUg/g; P <0.001). In UC, FC levels were lower in proctitis than in left-sided UC
      and pancolitis (340.0, 500.0, and 421.5 MUg/g, respectively), but the differences
      were not significant. In CD, lower FC values were observed in isolated small
      bowel disease. CONCLUSIONS FC levels increased dynamically even with mild signs
      of intestinal inflammation. The rapid Quantum Blue(r) test presents a potential
      alternative to the time-consuming ELISA, because its diagnostic accuracy is not
      influenced by disease location. It may be useful in the hospital setting,
      providing faster diagnosis and allowing cost reduction by lowering the number of
      endoscopic procedures.

PMID- 28442700
TI  - Role of the rs2274907 allelic variant of the ITLN1 gene in patients with diabetic
      foot.
AB  - INTRODUCTION Diabetic foot (DF) is a serious complication of diabetes mellitus
      (DM) that occurs due to neuropathy or atherosclerosis of the lower limbs. Omentin
      (encoded by the ITLN1 gene) has been implicated as a protective factor in
      vascular complications of diabetes, likely due to its endothelial vasodilator
      activity and its anti-inflammatory actions. However, susceptibility to DF with
      respect to the allelic variants of the ITLN1 gene has not been studied so far.
      OBJECTIVES This study aimed to evaluate the association between the rs2274907
      allelic variant of the ITLN1 gene and the occurrence of DF in patients with type
      2 diabetes mellitus (T2DM).  PATIENTS AND METHODS The study included 670
      individuals: 204 with T2DM and DF (DF group), 299 with T2DM without DF (T2DM
      group), and 167 healthy controls.  RESULTS Ischemic heart disease, retinopathy,
      nephropathy, neuropathy, obesity, hyperlipidemia, and active smoking were more
      frequent in the DF group than in the T2DM group. Allele A of the rs2274907
      variant was observed more frequently in the DF group compared with healthy
      controls in an additive model (odds ratio [OR] = 0.7, P = 0.034). This effect was
      also sex-specific for males in both the additive and recessive models (OR = 0.6,
      P = 0.015 and OR = 0.52, P = 0.0017, respectively). However, no differences in
      the distribution of alleles was observed between the DF and T2DM groups.
      CONCLUSIONS The rs2274907 variant of the ITLN1 gene is associated with increased
      prevalence of DF.

PMID- 28442701
TI  - A Case of Trigger-Point Injection-Induced Hypokalemic Paralysis.
AB  - BACKGROUND Trigger-point injection (TPI) therapy is an effective modality for
      symptomatic treatment of myofascial pain. Serious adverse effects are rarely
      observed. In this report, we present the case of a 39-year-old man who
      experienced severe, transient hypokalemic paralysis in the context of TPI therapy
      with methylprednisolone, bupivacaine, and epinephrine. He was successfully
      treated with electrolyte replacement in a closely monitored setting. CASE REPORT
      A 39-year-old man with no past medical history except for chronic left hip pain
      from a work-related injury received a TPI with methylprednisolone and
      bupivacaine. The TPI targeted the left iliopsoas tendon and was administered
      using ultrasound guidance. There were no immediately perceived complications, but
      within 12 h he presented with severe hypokalemic paralysis with a serum potassium
      1.7 mmol/L. Judicious potassium repletion was initiated. Repeated tests after 6 h
      consistently showed normal potassium levels of 4.5 mmol/L. CONCLUSIONS Severe
      hypokalemic paralysis in the context of trigger-point injection is an incredibly
      rare occurrence and this is the first case report in English literature. A high
      index of clinical suspicion and a systematic approach are therefore required for
      prompt diagnosis and management of this obscure iatrogenic entity. Clinicians can
      enhance patient safety by allowing the primary pathology to guide them.

PMID- 28442702
TI  - Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with
      Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A
      Study in a Chinese Uygur Population.
AB  - BACKGROUND Gene polymorphisms are associated with sensitivity to platinum drugs.
      This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2
      rs717620 locus, and the sensitivity of patients with advanced non-small cell lung
      cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. MATERIAL AND
      METHODS The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC
      patients were assessed by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). The relationship between the prognosis of advanced NSCLC
      Uygur patients and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was
      analyzed using progression-free survival (PFS) and overall survival (OS) as the
      major outcome indicators. RESULTS The median PFS of patients with advanced NSCLC
      was 6.9 months and the OS of Uygur patients with advanced NSCLC was 10.8 months.
      Kaplan-Meier survival analysis indicated that survival time of patients with
      GSTP1 AG + GG was significantly longer than in patients with AA gene (P<0.05),
      and survival time of patients with ABCC2 CT + TT was significantly longer than in
      patients with the CC gene (P<0.05). CONCLUSIONS Polymorphisms of GSTP1 rs1695 and
      ABCC2 rs717620 can be used to predict the outcomes of Uygur patients with
      advanced NSCLC who have received platinum-based chemotherapy. Additionally, this
      information could be used to guide the individualized treatment of Uygur patients
      with advanced NSCLC.

PMID- 28442703
TI  - Controllable and fast quantum-information transfer between distant nodes in two
      dimensional networks.
AB  - We construct shortcuts to adiabatic passage to achieve controllable and fast
      quantum-information transfer (QIT) between arbitrary two distant nodes in a two
      dimensional (2D) quantum network. Through suitable designing of time-dependent
      Rabi frequencies, we show that perfect QIT between arbitrary two distant nodes
      can be rapidly achieved. Numerical simulations demonstrate that the proposal is
      robust to the decoherence caused by atomic spontaneous emission and cavity photon
      leakage. Additionally, the proposed scheme is also insensitive to the variations
      of the experimental parameters. Thus, the proposed scheme provides a new
      perspective on robust quantum information processing in 2D quantum networks.

PMID- 28442704
TI  - Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an
      exosite-binding glycosylated substrate.
AB  - ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance
      of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10
      and ADAM17 inhibitor development has been focused on the discovery of compounds
      that bind the active site zinc, however, in recent years, there has been a shift
      from active site to secondary substrate binding site (exosite) inhibitor
      discovery in order to identify non-zinc-binding molecules. In the present work a
      glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to
      screen 370,276 compounds from the MLPCN collection. As a result of this uHTS
      effort, a selective, time-dependent, non-zinc-binding inhibitor of ADAM10 with Ki
      = 883 nM was discovered. This compound exhibited low cell toxicity and was able
      to selectively inhibit shedding of known ADAM10 substrates in several cell-based
      models. We hypothesize that differential glycosylation of these cognate
      substrates is the source of selectivity of our novel inhibitor. The data indicate
      that this novel inhibitor can be used as an in vitro and, potentially, in vivo,
      probe of ADAM10 activity. Additionally, results of the present and prior studies
      strongly suggest that glycosylated substrate are applicable as screening agents
      for discovery of selective ADAM probes and therapeutics.

PMID- 28442705
TI  - Model of electrical activity in cardiac tissue under electromagnetic induction.
AB  - Complex electrical activities in cardiac tissue can set up time-varying
      electromagnetic field. Magnetic flux is introduced into the Fitzhugh-Nagumo model
      to describe the effect of electromagnetic induction, and then memristor is used
      to realize the feedback of magnetic flux on the membrane potential in cardiac
      tissue. It is found that a spiral wave can be triggered and developed by setting
      specific initials in the media, that is to say, the media still support the
      survival of standing spiral waves under electromagnetic induction. Furthermore,
      electromagnetic radiation is considered on this model as external stimuli, it is
      found that spiral waves encounter breakup and turbulent electrical activities are
      observed, and it can give guidance to understand the occurrence of sudden heart
      disorder subjected to heavily electromagnetic radiation.

PMID- 28442706
TI  - Nitric Oxide (NO) Mediates the Inhibition of Form-Deprivation Myopia by Atropine
      in Chicks.
AB  - Myopia is the most common childhood refractive disorder. Atropine inhibits myopia
      progression, but its mechanism is unknown. Here, we show that myopia-prevention
      by atropine requires production of nitric oxide (NO). Form-deprivation myopia
      (FDM) was induced in week-old chicks by diffusers over the right eye (OD); the
      left eye (OS) remained ungoggled. On post-goggling days 1, 3, and 5, OD received
      intravitreally 20 uL of phosphate-buffered saline (vehicle), or vehicle plus: NO
      source: L-arginine (L-Arg, 60-6,000 nmol) or sodium nitroprusside (SNP, 10-1,000
      nmol); atropine (240 nmol); NO inhibitors: L-NIO or L-NMMA (6 nmol); negative
      controls: D-Arg (10 umol) or D-NMMA (6 nmol); or atropine plus L-NIO, L-NMMA, or
      D-NMMA; OS received vehicle. On day 6 post-goggling, refractive error, axial
      length, equatorial diameter, and wet weight were measured. Vehicle-injected
      goggled eyes developed significant FDM. This was inhibited by L-Arg (ED50 = 400
      nmol) or SNP (ED50 = 20 nmol), but not D-Arg. Higher-dose SNP, but not L-Arg, was
      toxic to retina/RPE. Atropine inhibited FDM as expected; adding NOS-inhibitors (L
      NIO, L-NMMA) to atropine inhibited this effect dose-dependently, but adding D
      NMMA did not. Equatorial diameter, wet weight, and metrics of control eyes were
      not affected by any treatment. In summary, intraocular NO inhibits myopia dose
      dependently and is obligatory for inhibition of myopia by atropine.

PMID- 28442707
TI  - Polyanionic Cyclodextrin Induced Supramolecular Nanoparticle.
AB  - Ionizable cyclodextrins have attracted increasing attention in host-guest
      chemistry and pharmaceutical industry, mainly due to the introduction of
      favorable electrostatic interactions. The ionizable cyclodextrins could not only
      enhance its own solubility but also induce oppositely charged guests to form more
      stable complex. However, the aggregation induced by charged cyclodextrins has
      rarely been reported. In this work, guided by the concept of molecular-induced
      aggregation, a series of carboxyl modified cyclodextrins were synthesized via
      "click" and hydrolysis reaction. Then, UV-vis spectrum was used to investigate
      the aggregating behaviors induced by these cyclodextrins towards the cationic
      guest molecules. The results showed that only the hepta-carboxyl-beta
      cyclodextrin could induce the guest molecules to self-assemble into
      supramolecular spherical nanoparticles. Meanwhile, it could form stable inclusion
      complex with amantadine, a drug for anti-Parkinson and antiviral. The assembly
      behaviors were investigated by dynamic light scattering, scanning electron
      microscope, atomic force microscope, transmission electron microscope and NMR
      spectroscopy. The supramolecular nanoparticles induced by hepta-carboxyl-beta-CD
      and its inclusion with amantadine could be used to encapsulate the model drug and
      achieve its controlled releasing behaviors.

PMID- 28442708
TI  - The complete 12 Mb genome and transcriptome of Nonomuraea gerenzanensis with new
      insights into its duplicated "magic" RNA polymerase.
AB  - In contrast to the widely accepted consensus of the existence of a single RNA
      polymerase in bacteria, several actinomycetes have been recently shown to possess
      two forms of RNA polymerases due the to co-existence of two rpoB paralogs in
      their genome. However, the biological significance of the rpoB duplication is
      obscure. In this study we have determined the genome sequence of the
      lipoglycopeptide antibiotic A40926 producer Nonomuraea gerenzanensis ATCC 39727,
      an actinomycete with a large genome and two rpoB genes, i.e. rpoB(S) (the wild
      type gene) and rpoB(R) (the mutant-type gene). We next analyzed the
      transcriptional and metabolite profiles in the wild-type gene and in two
      derivative strains over-expressing either rpoB(R) or a mutated form of this gene
      to explore the physiological role and biotechnological potential of the "mutant
      type" RNA polymerase. We show that rpoB(R) controls antibiotic production and a
      wide range of metabolic adaptive behaviors in response to environmental pH. This
      may give interesting perspectives also with regard to biotechnological
      applications.

PMID- 28442709
TI  - Evolutionary history of the extant amphioxus lineage with shallow-branching
      diversification.
AB  - Amphioxus or lancelets have been regarded as a key animal in understanding the
      origin of vertebrates. However, the evolutionary history within this lineage
      remains unexplored. As the amphioxus lineage has likely been separated from other
      chordates for a very long time and displays a marked left-right asymmetry, its
      evolutionary history is potentially helpful in better understanding chordate and
      vertebrate origins. We studied the phylogenetic relationships within the extant
      amphioxus lineage based on mitochondrial genomes incorporating new Asymmetron and
      Epigonichthys populations, and based on previously reported nuclear
      transcriptomes. The resulting tree patterns are consistent, showing the
      Asymmetron clade diverging first, followed by the Epigonichthys and Branchiostoma
      clades splitting. Divergence time estimates based on nuclear transcriptomes with
      vertebrate calibrations support a shallow diversification of the extant amphioxus
      lineage in the Tertiary. These estimates fit well with the closure of seaways
      between oceans by continental drift, ocean currents, and present geographical
      distributions, and suggest a long cryptic history from the origin of amphioxus to
      its most recent diversification. Deduced character polarities based on
      phylogenetic analyses suggest that the common ancestor of the extant amphioxus
      existed in a tiny epibenthic state with larva-like appearance of extant
      amphioxus, likely with ciliate epidermis.

PMID- 28442711
TI  - Temperature dependent fracture properties of shape memory alloys: novel findings
      and a comprehensive model.
AB  - Temperature dependent fracture properties of NiTi-based Shape Memory Alloys
      (SMAs), within the pseudoelastic regime, were analyzed. In particular, the
      effective Stress Intensity Factor (SIF) was estimated, at different values of the
      testing temperature, by a fitting of the William's expansion series, based on
      Digital Image Correlation (DIC) measurements. It was found that temperature plays
      an important role on SIF and on critical fast fracture conditions. As a
      consequence, Linear Elastic Fracture Mechanics (LEFM) approaches are not suitable
      to predict fracture properties of SMAs, as they do not consider the effects of
      temperature. On the contrary, good agreements between DIC results and the
      predictions of an ad-hoc analytical model were observed. In fact, the model takes
      into account the whole thermo mechanical loading condition, including both
      mechanical load and temperature. Results revealed that crack tip stress-induced
      transformations do not represent a toughening effect and this is a completely
      novel result within the SMA community. Furthremore, it was demonstrated that the
      analytical model can be actually used to define a temperature independent
      fracture toughness parameter. Therefore, a new approach is proposed, based on the
      analytical model, where both mechanical load and temperature are considered as
      loading parameters in SIF computation.

PMID- 28442710
TI  - Lsh/HELLS regulates self-renewal/proliferation of neural stem/progenitor cells.
AB  - Epigenetic mechanisms are known to exert control over gene expression and
      determine cell fate. Genetic mutations in epigenetic regulators are responsible
      for several neurologic disorders. Mutations of the chromatin remodeling protein
      Lsh/HELLS can cause the human Immunodeficiency, Centromere instability and Facial
      anomalies (ICF) syndrome, which is associated with neurologic deficiencies. We
      report here a critical role for Lsh in murine neural development. Lsh depleted
      neural stem/progenitor cells (NSPCs) display reduced growth, increases in
      apoptosis and impaired ability of self-renewal. RNA-seq analysis demonstrates
      differential gene expression in Lsh-/- NSPCs and suggests multiple aberrant
      pathways. Concentrating on specific genomic targets, we show that ablation of Lsh
      alters epigenetic states at specific enhancer regions of the key cell cycle
      regulator Cdkn1a and the stem cell regulator Bmp4 in NSPCs and alters their
      expression. These results suggest that Lsh exerts epigenetic regulation at key
      regulators of neural stem cell fate ensuring adequate NSPCs self-renewal and
      maintenance during development.

PMID- 28442713
TI  - A self-consistent spin-diffusion model for micromagnetics.
AB  - We propose a three-dimensional micromagnetic model that dynamically solves the
      Landau-Lifshitz-Gilbert equation coupled to the full spin-diffusion equation. In
      contrast to previous methods, we solve for the magnetization dynamics and the
      electric potential in a self-consistent fashion. This treatment allows for an
      accurate description of magnetization dependent resistance changes. Moreover, the
      presented algorithm describes both spin accumulation due to smooth magnetization
      transitions and due to material interfaces as in multilayer structures. The model
      and its finite-element implementation are validated by current driven motion of a
      magnetic vortex structure. In a second experiment, the resistivity of a magnetic
      multilayer structure in dependence of the tilting angle of the magnetization in
      the different layers is investigated. Both examples show good agreement with
      reference simulations and experiments respectively.

PMID- 28442712
TI  - Cardioprotective effects of Cu(II)ATSM in human vascular smooth muscle cells and
      cardiomyocytes mediated by Nrf2 and DJ-1.
AB  - Cu(II)ATSM was developed as a hypoxia sensitive positron emission tomography
      agent. Recent reports have highlighted the neuroprotective properties of
      Cu(II)ATSM, yet there are no reports that it confers cardioprotection. We
      demonstrate that Cu(II)ATSM activates the redox-sensitive transcription factor
      Nrf2 in human coronary artery smooth muscle cells (HCASMC) and cardiac myocytes
      (HCM), leading to upregulation of antioxidant defense enzymes. Oral delivery of
      Cu(II)ATSM in mice induced expression of the Nrf2-regulated enzymes in the heart
      and aorta. In HCASMC, Cu(II)ATSM increased expression of the Nrf2 stabilizer DJ
      1, and knockdown of Nrf2 or DJ-1 attenuated Cu(II)ATSM-mediated heme oxygenase-1
      and NADPH quinone oxidoreductase-1 induction. Pre-treatment of HCASMC with
      Cu(II)ATSM protected against the pro-oxidant effects of angiotensin II (Ang II)
      by attenuating superoxide generation, apoptosis, proliferation and increases in
      intracellular calcium. Notably, Cu(II)ATSM-mediated protection against Ang II
      induced HCASMC apoptosis was diminished by Nrf2 knockdown. Acute treatment with
      Cu(II)ATSM enhanced the association of DJ-1 with superoxide dismutase-1 (SOD1),
      paralleled by significant increases in intracellular Cu(II) levels and SOD1
      activity. We describe a novel mechanism by which Cu(II)ATSM induces Nrf2
      regulated antioxidant enzymes and protects against Ang II-mediated HCASMC
      dysfunction via activation of the Nrf2/DJ-1 axis. Cu(II)ATSM may provide a
      therapeutic strategy for cardioprotection via upregulation of antioxidant
      defenses.

PMID- 28442714
TI  - Mitigating Herding in Hierarchical Crowdsourcing Networks.
AB  - Hierarchical crowdsourcing networks (HCNs) provide a useful mechanism for social
      mobilization. However, spontaneous evolution of the complex resource allocation
      dynamics can lead to undesirable herding behaviours in which a small group of
      reputable workers are overloaded while leaving other workers idle. Existing
      herding control mechanisms designed for typical crowdsourcing systems are not
      effective in HCNs. In order to bridge this gap, we investigate the herding
      dynamics in HCNs and propose a Lyapunov optimization based decision support
      approach - the Reputation-aware Task Sub-delegation approach with dynamic worker
      effort Pricing (RTS-P) - with objective functions aiming to achieve superlinear
      time-averaged collective productivity in an HCN. By considering the workers'
      current reputation, workload, eagerness to work, and trust relationships, RTS-P
      provides a systematic approach to mitigate herding by helping workers make joint
      decisions on task sub-delegation, task acceptance, and effort pricing in a
      distributed manner. It is an individual-level decision support approach which
      results in the emergence of productive and robust collective patterns in HCNs.
      High resolution simulations demonstrate that RTS-P mitigates herding more
      effectively than state-of-the-art approaches.

PMID- 28442715
TI  - Work disability before and after a major cardiovascular event: a ten-year study
      using nationwide medical and insurance registers.
AB  - We examined the trajectories of work disability before and after IHD and stroke
      events. New IHD (n = 13521) and stroke (n = 7162) cases in 2006-2008 were
      retrieved from nationwide Swedish hospital records and their annual work
      disability days five years before and after the date of diagnosis were retrieved
      from a nationwide disability register. There was no pre-event differences in
      disability days between the IHD and stroke cases and five years prior to the
      event, they were close to those observed in the general population. In the first
      post-event year, the adjusted mean days increased to 83.9 (95% CI 80.6-86.5) in
      IHD; to 179.5 (95% CI 172.4-186.8) in stroke, a six-fold increase in IHD and 14
      fold in stroke. Work disability leveled off among the IHD cases but not among
      those who had stroke. The highest disability levels for the fifth post-event year
      after a stroke event was associated with pre-existing diabetes (146.9), mental
      disorder (141.2), non-employment (137.0), and immigrant status (117.9). In a
      working-age population, the increase in work disability after a cardiovascular
      event decreases close   to the pre-event level in IHD but remains particularly
      high after stroke; among patients with comorbid depression or diabetes,
      immigrants, and those not in employment.

PMID- 28442716
TI  - A Puccinia striiformis f. sp. tritici secreted protein activates plant immunity
      at the cell surface.
AB  - Pathogens secrete effector proteins to suppress host immunity, mediate nutrient
      uptake and subsequently enable parasitism. However, on non-adapted hosts,
      effectors can be detected as non-self by host immune receptors and activate non
      host immunity. Nevertheless, the molecular mechanisms of effector triggered non
      host resistance remain unknown. Here, we report that a small cysteine-rich
      protein PstSCR1 from the wheat rust pathogen Puccinia striiformis f. sp. tritici
      (Pst) activates immunity in the non-host solanaceous model plant Nicotiana
      benthamiana. PstSCR1 homologs were found to be conserved in Pst, and in its
      closest relatives, Puccinia graminis f. sp. tritici and Puccinia triticina. When
      PstSCR1 was expressed in N. benthamiana with its signal peptide, it provoked the
      plant immune system, whereas no stimulation was observed when it was expressed
      without its signal peptide. PstSCR1 expression in N. benthamiana significantly
      reduced infection capacity of the oomycete pathogens. Moreover, apoplast-targeted
      PstSCR1 triggered plant cell death in a dose dependent manner. However, in
      Brassinosteroid insensitive 1-Associated Kinase 1 (SERK3/BAK1) silenced N.
      benthamiana, cell death was remarkably decreased. Finally, purified PstSCR1
      protein activated defence related gene expression in N. benthamiana. Our results
      show that a Pst-secreted protein, PstSCR1 can activate surface mediated immunity
      in non-adapted hosts and contribute to non-host resistance.

PMID- 28442717
TI  - The biomarker and causal roles of homoarginine in the development of
      cardiometabolic diseases: an observational and Mendelian randomization analysis.
AB  - High L-homoarginine (hArg) levels are directly associated with several risk
      factors for cardiometabolic diseases whereas low levels predict increased
      mortality in prospective studies. The biomarker role of hArg in young adults
      remains unknown. To study the predictive value of hArg in the development of
      cardiometabolic risk factors and diseases, we utilized data on high-pressure
      liquid chromatography-measured hArg, cardiovascular risk factors, ultrasound
      markers of preclinical atherosclerosis and type 2 diabetes from the population
      based Young Finns Study involving 2,106 young adults (54.6% females, aged 24-39).
      We used a Mendelian randomization approach involving tens to hundreds of
      thousands of individuals to test causal associations. In our 10-year follow-up
      analysis, hArg served as an independent predictor for future hyperglycaemia (OR
      1.31, 95% CI 1.06-1.63) and abdominal obesity (OR 1.60, 95% 1.14-2.30) in men and
      type 2 diabetes in women (OR 1.55, 95% CI 1.02-2.41). The MR analysis revealed no
      evidence of causal associations between serum hArg and any of the studied
      cardiometabolic outcomes. In conclusion, lifetime exposure to higher levels of
      circulating hArg does not seem to alter cardiometabolic disease risk. Whether
      hArg could be used as a biomarker for identification of individuals at risk
      developing cardiometabolic abnormalities merits further investigation.

PMID- 28442718
TI  - Pressure-induced structural change in liquid GaIn eutectic alloy.
AB  - Synchrotron x-ray diffraction reveals a pressure induced crystallization at about
      3.4 GPa and a polymorphic transition near 10.3 GPa when compressed a liquid GaIn
      eutectic alloy up to ~13 GPa at room temperature in a diamond anvil cell. Upon
      decompression, the high pressure crystalline phase remains almost unchanged until
      it transforms to the liquid state at around 2.3 GPa. The ab initio molecular
      dynamics calculations can reproduce the low pressure crystallization and give
      some hints on the understanding of the transition between the liquid and the
      crystalline phase on the atomic level. The calculated pair correlation function
      g(r) shows a non-uniform contraction reflected by the different compressibility
      between the short (1st shell) and the intermediate (2nd to 4th shells). It is
      concluded that the pressure-induced liquid-crystalline phase transformation
      likely arises from the changes in local atomic packing of the nearest neighbors
      as well as electronic structures at the transition pressure.

PMID- 28442720
TI  - Lattice dynamics and elasticity for epsilon-plutonium.
AB  - Lattice dynamics and elasticity for the high-temperature epsilon phase (body
      centered cubic; bcc) of plutonium is predicted utilizing first-principles
      electronic structure coupled with a self-consistent phonon method that takes
      phonon-phonon interaction and strong anharmonicity into account. These
      predictions establish the first sensible lattice-dynamics and elasticity data on
      epsilon-Pu. The atomic forces required for the phonon scheme are highly accurate
      and derived from the total energies obtained from relativistic and parameter-free
      density-functional theory. The results appear reasonable but no data exist to
      compare with except those from dynamical mean-field theory that suggest epsilon
      plutonium is mechanically unstable. Fundamental knowledge and understanding of
      the high-temperature bcc phase, that is generally present in all actinide metals
      before melting, is critically important for a proper interpretation of the phase
      diagram as well as practical modeling of high-temperature properties.

PMID- 28442719
TI  - Chlamydia trachomatis neither exerts deleterious effects on spermatozoa nor
      impairs male fertility.
AB  - Chlamydia trachomatis is the most prevalent sexually transmitted bacterial
      infection. However, whether Chlamydia trachomatis has a negative impact on sperm
      quality and male fertility is still controversial. Herein, we report the effects
      on sperm quality of the in vitro exposure of spermatozoa to Chlamydia
      trachomatis, and also the effects of male genital infection on male fertility
      using an animal model. Human and mouse sperm were obtained from healthy donors
      and cauda epididimys from C57BL/6 mice, respectively. Highly motile human or
      mouse spermatozoa were in vitro exposed to C. trachomatis (serovar E or LGV) or
      C. muridarum, respectively. Then, sperm quality parameters were analyzed.
      Moreover, male fertility of Chlamydia muridarum infected male C57BL/6 mice was
      assessed. Human or murine sperm in vitro exposed to increasing bacterial
      concentrations or soluble factors from C. trachomatis or C. muridarum,
      respectively, did not show differences in sperm motility and viability,
      apoptosis, mitochondrial membrane potential, DNA fragmentation, ROS production
      and lipid peroxidation levels, when compared with control sperm (p > 0.05).
      Moreover, no differences in fertility parameters (potency, fecundity, fertility
      index, pre- and post-implantation loss) were observed between control and
      infected males. In conclusion, our results indicate that Chlamydia spp. neither
      directly exerts deleterious effects on spermatozoa nor impairs male fertility.

PMID- 28442721
TI  - Near-field surface plasmons on quasicrystal metasurfaces.
AB  - Excitation and manipulation of surface plasmons (SPs) are essential in developing
      cutting-edge plasmonic devices for medical diagnostics, biochemical spectroscopy
      and communications. The most common approach involves designing an array of
      periodic slits or grating apertures that enables coupling of the incident light
      to the SP modes. In recent years, plasmonic resonances, including extraordinary
      optical transmission through periodic arrays, quasicrystals and random aperture
      arrays, have been investigated in the free space. However, most of the studies
      have been limited to the far field detection of the transmission resonance. Here,
      we perform near-field measurements of the SPs on quasicrystal metasurfaces. We
      discover that the reciprocal vector determines the propagation modes of the SPs
      in the quasicrystal lattice which can be well explained by the quasi-momentum
      conservation rule. Our findings demonstrate vast potential in developing
      plasmonic metasurfaces with unique device functionalities that are controlled by
      the propagation modes of the SPs in quasicrystals.

PMID- 28442722
TI  - Mutational screening of SLC39A5, LEPREL1 and LRPAP1 in a cohort of 187 high
      myopia patients.
AB  - High myopia (HM) is a leading cause of mid-way blindness with a high heritability
      in East Asia. Although only a few disease genes have been reported, a small
      proportion of patients could be identified with genetic predispositions. In order
      to expand the mutation spectrum of the causative genes in Chinese adult
      population, we investigated three genes, SLC39A5, LEPREL1 and LRPAP1, in a cohort
      of 187 independent Chinese patients with high myopia. Sanger sequencing was used
      to find possible pathogenic mutations, which were further screened in normal
      controls. After a pipeline of database and predictive assessments filtering, we,
      thereby, identified totally seven heterozygous mutations in the three genes.
      Among them, three novel missense mutations, c.860C > T, p.Pro287Leu and c.956G >
      C, p.Arg319Thr in SLC39A5, c.1982A > G, p.Lys661Arg in LEPREL1, were identified
      as potentially causative mutations. Additionally, the two heterozygous mutations
      (c.1582G > A, p.Ala528Thr; c.1982A > G, p.Lys661Arg) in one patient in LEPREL1
      gene were reported in this study. Our findings will not only augment the mutation
      spectrum of these three genes, but also provide insights of the contribution of
      these genes to adult high myopia in Chinese. However, further studies are still
      needed to address the pathogenicity of each of the mutations reported in this
      study.

PMID- 28442723
TI  - Effects of elevated CO2 on the fitness and potential population damage of
      Helicoverpa armigera based on two-sex life table.
AB  - We evaluated the direct effects of three different atmospheric CO2 concentrations
      (380 ppm, 550 ppm and 750 ppm) on the population parameters of the cotton
      bollworm, Helicoverpa armigera fed an artificial diet. The life history and
      fitness of H. armigera were analyzed using an age-stage, two-sex life table. Our
      results showed significantly longer larval durations and lower female pupal
      weight under elevated CO2 than under ambient CO2. Additionally, the fecundity of
      H. armigera was lower under elevated CO2 than under ambient CO2. H. armigera
      reared under elevated CO2 conditions showed lower intrinsic and finite rates of
      increase but higher net consumption and finite consumption rates than H. armigera
      reared under ambient CO2 conditions. According to population projections, a much
      smaller total population size and reduced consumption capacities would be
      expected in an elevated CO2 atmosphere due to higher mortality and lower growth
      rate compared with ambient CO2 levels. These results indicate that the fitness of
      and potential damage caused by H. armigera would be affected by increased CO2
      relative to ambient CO2 concentrations. Additional studies on the long-term
      direct and indirect effects of elevated CO2 levels on H. armigera are still
      needed.

PMID- 28442724
TI  - Entanglement distribution in multi-particle systems in terms of unified entropy.
AB  - We investigate the entanglement distribution in multi-particle systems in terms
      of unified (q, s)-entropy. We find that for any tripartite mixed state, the
      unified (q, s)-entropy entanglement of assistance follows a polygamy relation.
      This polygamy relation also holds in multi-particle systems. Furthermore, a
      generalized monogamy relation is provided for unified (q, s)-entropy entanglement
      in the multi-qubit system.

PMID- 28442725
TI  - Physical Links: defining and detecting inter-chain entanglement.
AB  - Fluctuating filaments, from densely-packed biopolymers to defect lines in
      structured fluids, are prone to become interlaced and form intricate
      architectures. Understanding the ensuing mechanical and relaxation properties
      depends critically on being able to capture such entanglement in quantitative
      terms. So far, this has been an elusive challenge. Here we introduce the first
      general characterization of non-ephemeral forms of entanglement in linear curves
      by introducing novel descriptors that extend topological measures of linking from
      close to open curves. We thus establish the concept of physical links. This
      general method is applied to diverse contexts: equilibrated ring polymers,
      mechanically-stretched links and concentrated solutions of linear chains. The
      abundance, complexity and space distribution of their physical links gives access
      to a whole new layer of understanding of such systems and open new perspectives
      for others, such as reconnection events and topological simplification in
      dissipative fields and defect lines.

PMID- 28442726
TI  - Effects of the continuous use of organic manure and chemical fertilizer on soil
      inorganic phosphorus fractions in calcareous soil.
AB  - A 4-year field trial with three treatments and three types of annually rotated
      vegetables was conducted in calcareous soil in a greenhouse using a phosphorus
      (P) fractionation method based on the inorganic P fraction classification system
      described by Jiang-Gu. With the same nutrient input, vegetable yields and P
      uptake were more stable under the chemical fertilizer (CF) treatment than under
      the organic manure (OM) treatment, and the average utilization rate of P
      fertilizer (URP) values were 5.27% and 11.40% under the OM and CF treatments,
      respectively, over the 4 years. Compared with the values in 2009, the values of
      the inorganic P (Pi) fractionation, including Ca-P, Al-P and Fe-P, significantly
      increased over time by 310.89 mg.kg-1, 36.21 mg.kg-1, and 18.77 mg.kg-1,
      respectively, with OM treatment and by 86.92 mg.kg-1, 175.87 mg.kg-1, and 24.27
      mg.kg-1 with CF treatment. These results suggest that 1) large amounts of P were
      released from Ca2-P, Ca8-P and Al-P and were taken up by vegetables in the
      calcareous soil, and 2) the excessive application of P fertilizer, especially OM,
      resulted in a substantial accumulation of Pi (Ca2-P, Ca8-P and Al-P), which
      increased the risk of pollution from organic farming diffusing into the surface
      water.

PMID- 28442727
TI  - Remarkably High Mobility Thin-Film Transistor on Flexible Substrate by Novel
      Passivation Material.
AB  - High mobility thin-film transistor (TFT) is crucial for future high resolution
      and fast response flexible display. Remarkably high performance TFT, made at room
      temperature on flexible substrate, is achieved with record high field-effect
      mobility (MU FE ) of 345 cm2/Vs, small sub-threshold slope (SS) of 103 mV/dec,
      high on-current/off-current (I ON /I OFF ) of 7 * 106, and a low drain-voltage
      (VD) of 2 V for low power operation. The achieved mobility is the best reported
      data among flexible electronic devices, which is reached by novel HfLaO
      passivation material on nano-crystalline zinc-oxide (ZnO) TFT to improve both I
      ON and I OFF . From X-ray photoelectron spectroscopy (XPS) analysis, the non
      passivated device has high OH-bonding intensity in nano-crystalline ZnO, which
      damage the crystallinity, create charged scattering centers, and form potential
      barriers to degrade mobility.

PMID- 28442728
TI  - Hybrid Energy Storage of Ni(OH)2-coated N-doped Graphene Aerogel//N-doped
      Graphene Aerogel for the Replacement of NiCd and NiMH Batteries.
AB  - Although Nickel-Cadmium (NiCd) and Nickel-metal hydride (NiMH) batteries have
      been widely used, their drawbacks including toxic Cd and expensive La alloy at
      the negative electrodes, low energy density (40-60 Wh/kg for NiCd and 140-300
      Wh/L for NiMH), low power density (150 W/kg for NiCd and 1000 W/kg for NiMH), and
      low working potential (1.2 V) limit their applications. In this work, Cd and La
      alloy were replaced with N-doped reduced graphene oxide aerogel (N-rGOae)
      providing a hybrid energy storage (HES) having the battery and supercapacitor
      effects. The HES of Ni(OH)2-coated N-rGOae//N-rGOae provides 1.5 V, a specific
      energy of 146 Wh/kg, a maximum specific power of 7705 W/kg, and high capacity
      retention over 84.6% after 5000 cycles. The mass change at the positive electrode
      during charging/discharging is 8.5 ug cm-2 owing to the insertion/desertion of
      solvated OH- into the alpha-Ni(OH)2-coated N-rGOae. At the negative electrode,
      the mass change of the solvated K+, physically adsorbed/desorbed to the N-rGOae,
      is 7.5 MUg cm-2. In situ X-ray absorption spectroscopy (XAS) shows highly
      reversible redox reaction of alpha-Ni(OH)2. The as-fabricated device without
      using toxic Cd and expensive La alloy has a potential as a candidate of NiCd and
      NiMH.

PMID- 28442729
TI  - The MAPKKK and MAPKK gene families in banana: identification, phylogeny and
      expression during development, ripening and abiotic stress.
AB  - The mitogen-activated protein kinase (MAPK) cascade, which is a major signal
      transduction pathway widely distributed in eukaryotes, has an important function
      in plant development and stress responses. However, less information is known
      regarding the MAPKKK and MAPKK gene families in the important fruit crop banana.
      In this study, 10 MAPKK and 77 MAPKKK genes were identified in the banana genome,
      and were classified into 4 and 3 subfamilies respectively based on phylogenetic
      analysis. Majority of MAPKKK and MAPKK genes in the same subfamily shared similar
      gene structures and conserved motifs. The comprehensive transcriptome analysis
      indicated that MAPKKK-MAPKK genes is involved in tissue development, fruit
      development and ripening, and response to abiotic stress of drought, cold and
      salt in two banana genotypes. Interaction networks and co-expression assays
      demonstrated that MAPK signaling cascade mediated network participates in
      multiple stress signaling, which was strongly activated in Fen Jiao (FJ). The
      findings of this study advance understanding of the intricately transcriptional
      control of MAPKKK-MAPKK genes and provide robust candidate genes for further
      genetic improvement of banana.

PMID- 28442731
TI  - GLAG theory for superconducting property variations with A15 composition in Nb3Sn
      wires.
AB  - We present a model for the variation of the upper critical field H c2 with Sn
      content in A15-type Nb-Sn wires, within the Ginzburg-Landau-Abrikosov-Gor'kov
      (GLAG) theory frame. H c2 at the vicinity of the critical temperature T c is
      related quantitatively to the electrical resistivity rho, specific heat capacity
      coefficient gamma and T c. H c2 versus tin content is theoretically formulated
      within the GLAG theory, and generally reproduces the experiment results. As Sn
      content gradually approaches the stoichiometry, A15-type Nb-Sn undergoes a
      transition from the dirty limit to clean limit, split by the phase transformation
      boundary. The H-T phase boundary and pinning force show different behaviors in
      the cubic and tetragonal phase. We dipict the dependence of the composition
      gradient on the superconducting properties variation in the A15 layer, as well as
      the curved tail at vicinity of H c2 in the Kramer plot of the Nb3Sn wire. This
      helps understanding of the inhomogeneous-composition inducing discrepancy between
      the results by the state-of-art scaling laws and experiments.

PMID- 28442730
TI  - Exploration of the relationship between biogas production and microbial community
      under high salinity conditions.
AB  - High salinity frequently causes inhibition and even failure in anaerobic
      digestion. To explore the impact of increasing NaCl concentrations on biogas
      production, and reveal the microbial community variations in response to high
      salinity stress, the Illumina high-throughput sequencing technology was employed.
      The results showed that a NaCl concentration of 20 g/L (H group) exhibited a
      similar level of VFAs and specific CO2 production rate with that in the blank
      group, thus indicating that the bacterial activity in acidogenesis might not be
      inhibited. However, the methanogenic activity in the H group was significantly
      affected compared with that in the blank group, causing a 42.2% decrease in CH4
      production, a 37.12% reduction in the specific CH4 generation rate and a lower pH
      value. Illumina sequencing revealed that microbial communities between the blank
      and H groups were significantly different. Bacteroides, Clostridium and BA021
      uncultured were the dominant species in the blank group while some halotolerant
      genera, such as Thermovirga, Soehngenia and Actinomyces, dominated and
      complemented the hydrolytic and acidogenetic abilities in the H group.
      Additionally, the most abundant archaeal species included Methanosaeta,
      Methanolinea, Methanospirillum and Methanoculleus in both groups, but
      hydrogenotrophic methanogens showed a lower resistance to high salinity than
      aceticlastic methanogens.

PMID- 28442732
TI  - Human bipedal instability in tree canopy environments is reduced by "light touch"
      fingertip support.
AB  - Whether tree canopy habitats played a sustained role in the ecology of ancestral
      bipedal hominins is unresolved. Some argue that arboreal bipedalism was
      prohibitively risky for hominins whose increasingly modern anatomy prevented them
      from gripping branches with their feet. Balancing on two legs is indeed
      challenging for humans under optimal conditions let alone in forest canopy, which
      is physically and visually highly dynamic. Here we quantify the impact of forest
      canopy characteristics on postural stability in humans. Viewing a movie of
      swaying branches while standing on a branch-like bouncy springboard destabilised
      the participants as much as wearing a blindfold. However "light touch", a
      sensorimotor strategy based on light fingertip support, significantly enhanced
      their balance and lowered their thigh muscle activity by up to 30%. This
      demonstrates how a light touch strategy could have been central to our ancestor's
      ability to avoid falls and reduce the mechanical and metabolic cost of arboreal
      feeding and movement. Our results may also indicate that some adaptations in the
      hand that facilitated continued access to forest canopy may have complemented,
      rather than opposed, adaptations that facilitated precise manipulation and tool
      use.

PMID- 28442733
TI  - Unique prostate cancer-toxic polyketides from marine sediment-derived fungus
      Isaria felina.

PMID- 28442734
TI  - Sonochemical synthesis of pyrido[2,3-d:6,5-d']-dipyrimidines catalyzed by
      [HNMP]+[HSO4]- and their antimicrobial activity studies.
AB  - In this study, the one-pot four-component reaction of aromatic aldehyde, 2
      thiobarbituric acid, ammonium acetate in the presence of a catalytic amount of [H
      NMP]+[HSO4]- under ultrasonic irradiation in water is reported. In the present
      procedure, the pyrido[2,3-d:6,5-d']dipyrimidine derivatives were purely produced
      as valuable products. The process proved to be simple, environmentally friendly,
      efficient and high to excellent yielding. Moreover, some of the synthetic
      compounds were investigated and revealed important antimicrobial activity of
      prepared products.

PMID- 28442735
TI  - Novel antibiotic screening methods to awaken silent or cryptic secondary
      metabolic pathways in actinomycetes.
AB  - Streptomyces have the potential to produce more than 30 secondary metabolites;
      however, the expression of most metabolite biosynthetic gene clusters is cryptic
      or silent. Indeed, the expression of these genes is conditional and dependent on
      culture conditions. To activate such gene clusters, many methods have been
      developed. In this review, I describe two activation approaches developed in my
      laboratory: use of the activation mediator goadsporin and combined-culture.
      Goadsporin is a chemical substance isolated from Streptomyces sp. TP-A0584; it
      induces secondary metabolism and sporulation of many Streptomyces species.
      Combined-culture is a co-culture method to activate secondary metabolism in
      Streptomyces. The activator strains are mycolic acid-containing bacteria and ~90%
      of Streptomyces species show changes in secondary metabolism in combined-culture
      compared with pure culture. Thus, both methods may have applications in natural
      product-based drug discovery.

PMID- 28442736
TI  - Political determinants and Aboriginal and Torres Strait Islander women: don't
      leave your integrity at the political gate.

PMID- 28442737
TI  - Structural and biochemical insights of CypA and AIF interaction.
AB  - The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in
      the DNA degradation in response to various cellular stress conditions, such as
      oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro
      apoptotic form of AIF (AIF(Delta1-121)) mainly interacts with CypA through the
      amino acid region 370-394. The AIF(370-394) synthetic peptide inhibits complex
      formation in vitro by binding to CypA and exerts neuroprotection in a model of
      glutamate-mediated oxidative stress. Here, the binding site of AIF(Delta1-121)
      and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical
      studies, and a molecular model of the complex has been proposed. We show that
      AIF(370-394) interacts with CypA on the same surface recognized by AIF(Delta1
      121) protein and that the region is very close to the CypA catalytic pocket. Such
      region partially overlaps with the binding site of cyclosporin A (CsA), the
      strongest catalytic inhibitor of CypA. Our data point toward distinct CypA
      structural determinants governing the inhibitor selectivity and the differential
      biological effects of AIF and CsA, and provide new structural insights for
      designing CypA/AIF selective inhibitors with therapeutic relevance in
      neurodegenerative diseases.

PMID- 28442738
TI  - Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast
      cancer invasion.
AB  - ErbB2 overexpression is detected in approximately 20% of breast cancers and is
      correlated with poor survival. It was previously shown that the adaptor protein
      p130Cas/BCAR1 is a crucial mediator of ErbB2 transformation and that its
      overexpression confers invasive properties to ErbB2-positive human mammary
      epithelial cells. We herein prove, for the first time, that the transcriptional
      repressor Blimp1 is a novel mediator of p130Cas/ErbB2-mediated invasiveness.
      Indeed, high Blimp1 expression levels are detected in invasive p130Cas/ErbB2
      cells and correlate with metastatic status in human breast cancer patients. The
      present study, by using 2D and 3D breast cancer models, shows that the increased
      Blimp1 expression depends on both MAPK activation and miR-23b downmodulation.
      Moreover, we demonstrate that Blimp1 triggers cell invasion and metastasis
      formation via its effects on focal adhesion and survival signaling. These
      findings unravel the previously unidentified role that transcriptional repressor
      Blimp1 plays in the control of breast cancer invasiveness.

PMID- 28442739
TI  - Mixing of quantum states: A new route to creating optical activity.
AB  - The ability to induce optical activity in nanoparticles and dynamically control
      its strength is of great practical importance due to potential applications in
      various areas, including biochemistry, toxicology, and pharmaceutical science.
      Here we propose a new method of creating optical activity in originally achiral
      quantum nanostructures based on the mixing of their energy states of different
      parities. The mixing can be achieved by selective excitation of specific states
      or via perturbing all the states in a controllable fashion. We analyze the
      general features of the so produced optical activity and elucidate the conditions
      required to realize the total dissymmetry of optical response. The proposed
      approach is applicable to a broad variety of real systems that can be used to
      advance chiroptical devices and methods.

PMID- 28442740
TI  - Deciphering the mode of action of cell wall-inhibiting antibiotics using
      metabolic labeling of growing peptidoglycan in Streptococcus pyogenes.
AB  - Because of the scanty pipeline of antibiotics newly obtained from nature,
      chemical modification of established drugs is one of the major streams of current
      antibacterial research. Intuitive and easy-to-use assays are critical for
      identifying drug candidates with novel modes of action. In this study, we
      demonstrated that metabolic fluorescent staining of growing cell walls is a
      powerful tool for mode-of-action analyses of antibiotics using Streptococcus
      pyogenes. A set of major cell-wall-inhibiting antibiotics (bacitracin, D
      cycloserine, flavomycin, oxacillin, ramoplanin, and vancomycin) was employed to
      validate the potential of the assay. The mechanistic differences of these
      antibiotics were successfully observed. For instance, D-cycloserine treatment
      induced fluorescently stained, excessive peripheral cell wall growth. This may
      indicate that the switch from the peripheral growth stage to the succeeding
      septal growth was disturbed by the treatment. We then applied this assay to
      analyze a series of vancomycin derivatives. The assay was sufficiently sensitive
      to detect the effects of single-site chemical modification of vancomycin on its
      modes of action. This metabolic fluorescent labeling method is easy to perform,
      especially because it does not require radiolabeled substrates. Thus, it is
      suitable for the preliminary evaluation of antibacterial mechanisms during
      antibacterial research.

PMID- 28442741
TI  - Polarization conversion when focusing cylindrically polarized vortex beams.
AB  - Currently, cylindrical beams with radial or azimuthal polarization are being used
      successfully for the optical manipulation of micro- and nano-particles as well as
      in microscopy, lithography, nonlinear optics, materials processing, and
      telecommunication applications. The creation of these laser beams is carried out
      using segmented polarizing plates, subwavelength gratings, interference, or light
      modulators. Here, we demonstrate the conversion of cylindrically polarized laser
      beams from a radial to an azimuthal polarization, or vice versa, by introducing a
      higher-order vortex phase singularity. To simultaneously generate several vortex
      phase singularities of different orders, we utilized a multi-order diffractive
      optical element. Both the theoretical and the experimental results regarding the
      radiation transmitted through the diffractive optical element show that
      increasing the order of the phase singularity leads to more efficient
      conversation of the polarization from radial to azimuthal. This demonstrates a
      close connection between the polarization and phase states of electromagnetic
      beams, which has important implications in many optical experiments.

PMID- 28442742
TI  - Non-volatile logic gates based on planar Hall effect in magnetic films with two
      in-plane easy axes.
AB  - We discuss the use of planar Hall effect (PHE) in a ferromagnetic GaMnAs film
      with two in-plane easy axes as a means for achieving novel logic functionalities.
      We show that the switching of magnetization between the easy axes in a GaMnAs
      film depends strongly on the magnitude of the current flowing through the film
      due to thermal effects that modify its magnetic anisotropy. Planar Hall
      resistance in a GaMnAs film with two in-plane easy axes shows well-defined maxima
      and minima that can serve as two binary logic states. By choosing appropriate
      magnitudes of the input current for the GaMnAs Hall device, magnetic logic
      functions can then be achieved. Specifically, non-volatile logic functionalities
      such as AND, OR, NAND, and NOR gates can be obtained in such a device by
      selecting appropriate initial conditions. These results, involving a simple PHE
      device, hold promise for realizing programmable logic elements in magnetic
      electronics.

PMID- 28442743
TI  - Impact of pneumonia and lung cancer on mortality of women with hypertension.
AB  - Essential hypertension is one of the most severe women's health problems. Modern
      life brings more chances of pulmonary diseases to human. The purpose of the study
      is to investigate weather pneumonia and lung cancer are associated with the
      mortality of women with hypertension in different age. A cross-sectional
      retrospective study was conducted in women with hypertension, who were admitted
      into our hospital in 2004-2013. 14219 women were enrolled and 68.8 +/- 12.2 year
      old (y). Isolated hypertension was 14.7%. The age of death was 78.1 +/- 9.8 y.
      The mortality was 4.4% for average and 0.2%, 1.1%, 2.4%, 4.8%, 10.4% and 15.8% in
      group age ?49, 50-59, 60-69, 70-79, 80-89 and ?90 y separately. This mortality
      increased with age was positively significantly correlated with the increased
      incidences of pneumonia (P < 0.05, r = 0.77). Pneumonia was a significant risk
      associated with the mortality in age 55-89 y (OR = 6.4-22.5; 95% CI = 3.06
      51.12). While, lung cancer was the significant risk in 70-79 y. These
      observations indicate that pneumonia and lung cancer are significant risk factors
      associated with the mortality of certain age women with hypertension, and bring
      an alert that pneumonia and lung cancer should be prevented and treated
      intensively in modern life in order to reduce the mortality.

PMID- 28442744
TI  - Biomimetic antimicrobial cloak by graphene-oxide agar hydrogel.
AB  - Antibacterial surfaces have an enormous economic and social impact on the
      worldwide technological fight against diseases. However, bacteria develop
      resistance and coatings are often not uniform and not stable in time. The
      challenge is finding an antibacterial coating that is biocompatible, cost
      effective, not toxic, and spreadable over large and irregular surfaces. Here we
      demonstrate an antibacterial cloak by laser printing of graphene oxide hydrogels
      mimicking the Cancer Pagurus carapace. We observe up to 90% reduction of bacteria
      cells. This cloak exploits natural surface patterns evolved to resist to
      microorganisms infection, and the antimicrobial efficacy of graphene oxide. Cell
      integrity analysis by scanning electron microscopy and nucleic acids release show
      bacteriostatic and bactericidal effect. Nucleic acids release demonstrates
      microorganism cutting, and microscopy reveals cells wrapped by the laser treated
      gel. A theoretical active matter model confirms our findings. The employment of
      biomimetic graphene oxide gels opens unique possibilities to decrease infections
      in biomedical applications and chirurgical equipment; our antibiotic-free
      approach, based on the geometric reduction of microbial adhesion and the
      mechanical action of Graphene Oxide sheets, is potentially not affected by
      bacterial resistance.

PMID- 28442745
TI  - Phosphorylation of the mitochondrial autophagy receptor Nix enhances its
      interaction with LC3 proteins.
AB  - The mitophagy receptor Nix interacts with LC3/GABARAP proteins, targeting
      mitochondria into autophagosomes for degradation. Here we present evidence for
      phosphorylation-driven regulation of the Nix:LC3B interaction. Isothermal
      titration calorimetry and NMR indicate a ~100 fold enhanced affinity of the
      serine 34/35-phosphorylated Nix LC3-interacting region (LIR) to LC3B and
      formation of a very rigid complex compared to the non-phosphorylated sequence.
      Moreover, the crystal structure of LC3B in complex with the Nix LIR peptide
      containing glutamic acids as phosphomimetic residues and NMR experiments revealed
      that LIR phosphorylation stabilizes the Nix:LC3B complex via formation of two
      additional hydrogen bonds between phosphorylated serines of Nix LIR and Arg11,
      Lys49 and Lys51 in LC3B. Substitution of Lys51 to Ala in LC3B abrogates binding
      of a phosphomimetic Nix mutant. Functionally, serine 34/35 phosphorylation
      enhances autophagosome recruitment to mitochondria in HeLa cells. Together, this
      study provides cellular, biochemical and biophysical evidence that
      phosphorylation of the LIR domain of Nix enhances mitophagy receptor engagement.

PMID- 28442747
TI  - Soret and Dufour effects on unsteady mixed convection slip flow of Casson fluid
      over a nonlinearly stretching sheet with convective boundary condition.
AB  - Unsteady mixed convection flow of Casson fluid towards a nonlinearly stretching
      sheet with the slip and convective boundary conditions is analyzed in this work.
      The effects of Soret Dufour, viscous dissipation and heat generation/absorption
      are also investigated. After using some suitable transformations, the unsteady
      nonlinear problem is solved by using Keller-box method. Numerical solutions for
      wall shear stress and high temperature transfer rate are calculated and compared
      with previously published work, an excellent arrangement is followed. It is
      noticed that fluid velocity reduces for both local unsteadiness and Casson
      parameters. It is likewise noticed that the influence of a Dufour number of
      dimensionless temperature is more prominent as compared to species concentration.
      Furthermore, the temperature was found to be increased in the case of nonlinear
      thermal radiation.

PMID- 28442746
TI  - Ultrastructural Characterization of the Lower Motor System in a Mouse Model of
      Krabbe Disease.
AB  - Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of beta-
      galactosylceramidase enzymatic activity and by widespread accumulation of the
      cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells.
      Despite the wide use of Twitcher mice as experimental model for KD, the
      ultrastructure of this model is partial and mainly addressing peripheral nerves.
      More details are requested to elucidate the basis of the motor defects, which are
      the first to appear during KD onset. Here we use transmission electron microscopy
      (TEM) to focus on the alterations produced by KD in the lower motor system at
      postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30
      mouse. We find mild effects on motorneuron soma, severe ones on sciatic nerves
      and very severe effects on nerve terminals and neuromuscular junctions at P30,
      with peripheral damage being already detectable at P15. Finally, we find that the
      gastrocnemius muscle undergoes atrophy and structural changes that are
      independent of denervation at P15. Our data further characterize the
      ultrastructural analysis of the KD mouse model, and support recent theories of a
      dying-back mechanism for neuronal degeneration, which is independent of
      demyelination.

PMID- 28442748
TI  - Pentamethylquercetin induces adipose browning and exerts beneficial effects in
      3T3-L1 adipocytes and high-fat diet-fed mice.
AB  - Browning white adipocytes may be a new target in anti-obesity therapy.
      Pentamethylquercetin (PMQ) has been shown to have anti-obesity effects in
      monosodium glutamate-induced obese mice. Here, we aimed to study the anti-obesity
      effects of PMQ in vitro and in vivo and to determine if adipose browning is
      involved in the mechanism underlying the anti-obesity effects of PMQ. We
      evaluated the effects of PMQ on cell proliferation, cell differentiation, glucose
      consumption, cellular lipid metabolism, and related brown gene expression in 3T3
      L1 adipocytes. We also investigated the effects of PMQ in a mouse model of high
      fat diet (HFD)-induced obesity. Our results demonstrated that PMQ increased the
      consumption of glucose, inhibited the accumulation of cellular triglycerides
      (TGs), and induced the expression of brown adipocyte-specific genes, such as
      uncoupling protein 1 (UCP-1), during the early stage of differentiation in 3T3-L1
      adipocytes. In HFD mice, PMQ treatment reduced waist circumference, LEE index,
      white adipose tissue (WAT) weight and white adipocyte size and increased brown
      adipose tissue (BAT) weight. Moreover, PMQ treatment induced mitochondrial
      biogenesis and upregulated UCP-1 expression in WAT. These findings suggest that
      PMQ may induce browning of adipose tissue, a phenomenon that is at least partly
      related to its anti-obesity effects.

PMID- 28442749
TI  - Identification of drug candidates that enhance pyrazinamide activity from a
      clinical compound library.

PMID- 28442750
TI  - Hepatitis A virus infections and outbreaks in asylum seekers arriving to Germany,
      September 2015 to March 2016.
AB  - From September 2015 to March 2016, hepatitis A notifications in Germany increased
      by 45% to 699 cases compared to 482 cases in the same period of the previous
      year. Children aged five to nine years were predominantly affected (22% of all
      cases in this period). We hypothesized that this increase could be explained by
      the marked influx of asylum seekers in this time period. We analysed national
      surveillance data and estimated the number of imported and autochthonous
      hepatitis A cases in asylum seekers. We also investigated molecular signatures of
      hepatitis A viruses sampled from asylum seekers to identify chains of
      transmission. We found that 40% (278 cases) of all 699 hepatitis A cases notified
      between September 2015 and March 2016 in Germany concerned asylum seekers. Most
      infections were acquired abroad, but at least 24% accounted for autochthonous
      infections. Among asylum seekers, children aged five to nine years were
      overrepresented with 97 of 278 (35%) notified cases. The analysed hepatitis A
      virus sequences were primarily subgenotype IB strains and clustered with
      previously isolated samples from the Middle East, Turkey, Pakistan and East
      Africa. Except one transmission from an asymptomatic child to a nursery nurse
      working in a mass accommodation, we are not aware of infection chains involving
      asylum seekers and German residents. We conclude that asylum-seeking children and
      adolescents are susceptible to hepatitis A virus infections, particularly
      children aged five to nine years. Measures to prevent secondary infections in
      asylum seekers such as extended hygiene measures and post-exposure prophylaxis
      seem advisable.

PMID- 28442751
TI  - Varying effects of common tuberculosis drugs on enhancing clofazimine activity in
      vitro.

PMID- 28442753
TI  - Precision immunomedicine.

PMID- 28442752
TI  - Zika virus infection reprograms global transcription of host cells to allow
      sustained infection.
AB  - Zika virus (ZIKV) is an emerging virus causally linked to neurological disorders,
      including congenital microcephaly and Guillain-Barre syndrome. There are
      currently no targeted therapies for ZIKV infection. To identify novel antiviral
      targets and to elucidate the mechanisms by which ZIKV exploits the host cell
      machinery to support sustained replication, we analyzed the transcriptomic
      landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived
      macrophage cell lines before and after ZIKV infection. The four cell types
      differed in their susceptibility to ZIKV infection, consistent with differences
      in their expression of viral response genes before infection. Clustering and
      network analyses of genes differentially expressed after ZIKV infection revealed
      changes related to the adaptive immune system, angiogenesis and host metabolic
      processes that are conducive to sustained viral production. Genes related to the
      adaptive immune response were downregulated in microglia cells, suggesting that
      ZIKV effectively evades the immune response after reaching the central nervous
      system. Like other viruses, ZIKV diverts host cell resources and reprograms the
      metabolic machinery to support RNA metabolism, ATP production and glycolysis.
      Consistent with these transcriptomic analyses, nucleoside metabolic inhibitors
      abrogated ZIKV replication in microglia cells.

PMID- 28442754
TI  - Vector competence and transovarial transmission of two Aedes aegypti strains to
      Zika virus.
AB  - Zika virus (ZIKV) has become a serious threat to global health since the outbreak
      in Brazil in 2015. Additional Chinese cases have continuously been reported since
      the first case of laboratory-confirmed ZIKV infection in China on 6 February
      2016. Aedes aegypti is the most important vector for ZIKV. This study shows that
      two strains from China exhibit high levels of midgut infection and highly
      disseminated infection of salivary glands and ovaries. Both strains can transmit
      ZIKV to infant mice bitten by infectious mosquitoes. Moreover, the results
      provide the evidence of transovarial transmission of ZIKV in mosquitoes. The
      study indicates that the two Ae. aegypti strains are not only effective
      transmission vectors but also persistent survival hosts for ZIKV during
      unfavorable inter-epidemic periods. This function as a reservoir of infection has
      epidemiological implications that further enhance the risk of potential future
      outbreaks.

PMID- 28442755
TI  - Global and local environmental changes as drivers of Buruli ulcer emergence.
AB  - Many emerging infectious diseases are caused by generalist pathogens that infect
      and transmit via multiple host species with multiple dissemination routes, thus
      confounding the understanding of pathogen transmission pathways from wildlife
      reservoirs to humans. The emergence of these pathogens in human populations has
      frequently been associated with global changes, such as socio-economic, climate
      or biodiversity modifications, by allowing generalist pathogens to invade and
      persist in new ecological niches, infect new host species, and thus change the
      nature of transmission pathways. Using the case of Buruli ulcer disease, we
      review how land-use changes, climatic patterns and biodiversity alterations
      contribute to disease emergence in many parts of the world. Here we clearly show
      that Mycobacterium ulcerans is an environmental pathogen characterized by multi
      host transmission dynamics and that its infectious pathways to humans rely on the
      local effects of global environmental changes. We show that the interplay between
      habitat changes (for example, deforestation and agricultural land-use changes)
      and climatic patterns (for example, rainfall events), applied in a local context,
      can lead to abiotic environmental changes and functional changes in local
      biodiversity that favor the pathogen's prevalence in the environment and may
      explain disease emergence.

PMID- 28442756
TI  - Crystal structure-based discovery of a novel synthesized PARP1 inhibitor (OL-1)
      with apoptosis-inducing mechanisms in triple-negative breast cancer.
AB  - Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on
      the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors
      have been reported and used for breast cancer therapy in recent years, especially
      in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton
      is alternatively promising strategy for TNBC therapy. In this study, based on co
      crystallization studies and pharmacophore-docking-based virtual screening, we
      discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors.
      Lead optimization result in the identification of compound OL-1 (2-(11-(3
      (dimethylamino)propylidene)-6,11- dihydrodibenzo[b,e]oxepin )-2
      yl)acetohydrazide), which has a novel chemical scaffold and unique binding
      interaction with PARP1 protein. OL-1 demonstrated excellent potency (inhibiting
      PARP1 enzyme activity with IC50 = 0.079 MUM), as well as inhibiting PARP
      modulated PARylation and cell proliferation in MDA-MB-436 cells (BRAC1 mutation).
      In addition, OL-1 also inhibited cell migration that closely related to cancer
      metastasis and displayed remarkable anti-tumor efficacy in MDA-MB-436 xenograft
      model without apparent toxicities. These findings highlight a new small-molecule
      PAPR1 inhibitor (OL-1) that has the potential to impact future TNBC therapy.

PMID- 28442757
TI  - Comparison of Circulating Tumour Cells and Circulating Cell-Free Epstein-Barr
      Virus DNA in Patients with Nasopharyngeal Carcinoma Undergoing Radiotherapy.
AB  - Quantification of Epstein-Barr virus (EBV) cell-free DNA (cfDNA) is commonly used
      in clinical settings as a circulating biomarker in nasopharyngeal carcinoma
      (NPC), but there has been no comparison with circulating tumour cells (CTCs). Our
      study aims to compare the performance of CTC enumeration against EBV cfDNA
      quantitation through digital PCR (dPCR) and quantitative PCR. 74 plasma samples
      from 46 NPC patients at baseline and one month after radiotherapy with or without
      concurrent chemotherapy were analysed. CTCs were captured by microsieve
      technology and enumerated, while three different methods of EBV cfDNA
      quantification were applied, including an in-house qPCR assay for BamHI-W
      fragment, a CE-IVD qPCR assay (Sentosa (r)) and a dPCR (ClarityTM) assay for
      Epstein-Barr nuclear antigen 1 (EBNA1). EBV cfDNA quantitation by all workflows
      showed stronger correlation with clinical stage, radiological response and
      overall survival in comparison with CTC enumeration. The highest detection rate
      of EBV cfDNA in pre-treatment samples was seen with the BamHI-W qPCR assay (89%),
      followed by EBNA1-dPCR (85%) and EBNA1-qPCR (67%) assays. Overall, we show that
      EBV cfDNA outperforms CTC enumeration in correlation with clinical outcomes of
      NPC patients undergoing treatment. Techniques such as dPCR and target selection
      of BamHI-W may improve sensitivity for EBV cfDNA detection.

PMID- 28442758
TI  - An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for
      mycobacterial cell division.
AB  - Mycobacteria possess a multi-layered cell wall that requires extensive
      remodelling during cell division. We investigated the role of an amidase_3 domain
      containing N-acetylmuramyl-L-alanine amidase, a peptidoglycan remodelling enzyme
      implicated in cell division. We demonstrated that deletion of MSMEG_6281 (Ami1)
      in Mycobacterium smegmatis resulted in the formation of cellular chains,
      illustrative of cells that were unable to complete division. Suprisingly,
      viability in the Deltaami1 mutant was maintained through atypical lateral
      branching, the products of which proceeded to form viable daughter cells. We
      showed that these lateral buds resulted from mislocalization of DivIVA, a major
      determinant in facilitating polar elongation in mycobacterial cells. Failure of
      Deltaami1 mutant cells to separate also led to dysregulation of FtsZ ring
      bundling. Loss of Ami1 resulted in defects in septal peptidoglycan turnover with
      release of excess cell wall material from the septum or newly born cell poles. We
      noted signficant accumulation of 3-3 crosslinked muropeptides in the Deltaami1
      mutant. We further demonstrated that deletion of ami1 leads to increased cell
      wall permeability and enhanced susceptiblity to cell wall targeting antibiotics.
      Collectively, these data provide novel insight on cell division in actinobacteria
      and highlights a new class of potential drug targets for mycobacterial diseases.

PMID- 28442760
TI  - Localization of Laplacian eigenvectors on random networks.
AB  - In large random networks, each eigenvector of the Laplacian matrix tends to
      localize on a subset of network nodes having similar numbers of edges, namely,
      the components of each Laplacian eigenvector take relatively large values only on
      a particular subset of nodes whose degrees are close. Although this localization
      property has significant consequences for dynamical processes on random networks,
      a clear theoretical explanation has not yet been established. Here we analyze the
      origin of localization of Laplacian eigenvectors on random networks by using a
      perturbation theory. We clarify how heterogeneity in the node degrees leads to
      the eigenvector localization and that there exists a clear degree-eigenvalue
      correspondence, that is, the characteristic degrees of the localized nodes
      essentially determine the eigenvalues. We show that this theory can account for
      the localization properties of Laplacian eigenvectors on several classes of
      random networks, and argue that this localization should occur generally in
      networks with degree heterogeneity.

PMID- 28442759
TI  - A statistical algorithm showing coenzyme Q10 and citrate synthase as biomarkers
      for mitochondrial respiratory chain enzyme activities.
AB  - Laboratory data interpretation for the assessment of complex biological systems
      remains a great challenge, as occurs in mitochondrial function research studies.
      The classical biochemical data interpretation of patients versus reference values
      may be insufficient, and in fact the current classifications of mitochondrial
      patients are still done on basis of probability criteria. We have developed and
      applied a mathematic agglomerative algorithm to search for correlations among the
      different biochemical variables of the mitochondrial respiratory chain in order
      to identify populations displaying correlation coefficients >0.95. We
      demonstrated that coenzyme Q10 may be a better biomarker of mitochondrial
      respiratory chain enzyme activities than the citrate synthase activity.
      Furthermore, the application of this algorithm may be useful to re-classify
      mitochondrial patients or to explore associations among other biochemical
      variables from different biological systems.

PMID- 28442761
TI  - Generation of mutation hotspots in ageing bacterial colonies.
AB  - How do ageing bacterial colonies generate adaptive mutants? Over a period of two
      months, we isolated on ageing colonies outgrowing mutants able to use a new
      carbon source, and sequenced their genomes. This allowed us to uncover exquisite
      details on the molecular mechanism behind their adaptation: most mutations were
      located in just a few hotspots in the genome, and over time, mutations
      increasingly were consistent with the involvement of 8-oxo-guanosine, formed
      exclusively on the transcribed strand. This work provides strong support for
      retromutagenesis as a general process creating adaptive mutations during ageing.

PMID- 28442762
TI  - First, you need a Gestalt: An interaction of bottom-up and top-down streams
      during the perception of the ambiguously rotating human walker.
AB  - Our visual system combines sensory evidence with prior knowledge to produce a
      representation of an outside world. Here, we explored the limits of the
      feedforward computation using an ambiguously rotating human biological motion.
      Specifically, we investigated whether an overall rotation, which was added to all
      the displays used in the study, would be perceived when the point-light walker
      was presented upside-down, a condition that typically obliterates perception of a
      human Gestalt. We report that inversion of the point-light walker or the absence
      of an identifiable Gestalt abolished the perception of an overall rotation.
      Perception of rotation was restored if the human walker Gestalt could be
      identified (an upright walker), if observers were informed about the nature of
      the motion display, or if observers expected to see the rotation of an unknown
      dynamic object. This implies that a mathematically more complex human motion was
      accounted for before the remaining motion components could be used to infer an
      overall rotation. Our results indicate that the perceptual inference does not
      proceed in a hierarchical manner with the simpler components being identified
      first. Instead, prior knowledge acts as a starting point for the decomposition of
      an even relatively simple combination of two motions.

PMID- 28442763
TI  - Impact of hormone receptor status and distant recurrence-free interval on
      survival benefits from trastuzumab in HER2-positive metastatic breast cancer.
AB  - We sought to investigate the impact of hormone receptor (HR) status and distant
      recurrence-free interval (DRFI) on the degree of overall survival (OS) benefit
      from palliative trastuzumab-containing treatment in HER2-positive metastatic
      breast cancer (MBC). Here, we retrospectively identified 588 eligible HER2
      positive patients with postoperative distant recurrence. DRFI of HR+HER2+ MBC
      patients (median: 30.7 months, IQR: 18.5-45.9, P < 0.001) was significant longer
      compared with HR-HER2+ patients. Patients were categorized into four subgroups
      based on HR status and palliative trastuzumab (trast+) received. The most
      superior outcome was observed in the HR+HER2+trast+ subgroup, with a median OS of
      48.3 months. Moreover, DRFI > 24 months is an independent favourable prognostic
      factor for both HR-HER2+ patients (Hazard Ratio (HzR) = 0.55, 95% CI: 0.39-0.76,
      P < 0.001) and HR+HER2+ patients (HzR = 0.45, 95% CI: 0.32-0.64, P  <  0.001).
      Upon further analysis of the interaction between trastuzumab and DRFI, the degree
      of trastuzumab benefits in HR-HER2+ MBC patients remained basically unchanged
      regardless of DRFI length. Unlikely, the degree in HR+HER2+ MBC patients
      decreased gradually along with DRFI extending, indicating that trastuzumab failed
      to translate into an OS benefit for late recurrent (DRFI > 5years) HR+HER2+ MBC
      patients.

PMID- 28442764
TI  - Evolution of the intrinsic electronic phase separation in La0.6Er0.1Sr0.3MnO3
      perovskite.
AB  - Magnetic and electronic transport properties of perovskite manganite
      La0.6Er0.1Sr0.3MnO3 have been thoroughly examined through the measurements of
      magnetization, electron paramagnetic resonance(EPR), and resistivity. It was
      found that the substitution of Er3+ for La3+ ions introduced the chemical
      disorder and additional strain in this sample. An extra resonance signal occurred
      in EPR spectra at high temperatures well above T C gives a strong evidence of
      electronic phase separation(EPS). The analysis of resistivity enable us to
      identify the polaronic transport mechanism in the paramagnetic region. At low
      temperature, a new ferromagnetic interaction generates in the microdomains of
      Er3+-disorder causing the second increase of magnetization. However, the new
      ferromagnetic interaction does not improve but decreases electronic transport due
      to the enhancement of interface resistance among neighboring domains. In view of
      a really wide temperature region for the EPS existence, this sample provides an
      ideal platform to uncover the evolution law of different magnetic structures in
      perovskite manganites.

PMID- 28442765
TI  - The GPR139 reference agonists 1a and 7c, and tryptophan and phenylalanine share a
      common binding site.
AB  - GPR139 is an orphan G protein-coupled receptor expressed in the brain, in
      particular in the habenula, hypothalamus and striatum. It has therefore been
      suggested that GPR139 is a possible target for metabolic disorders and
      Parkinson's disease. Several surrogate agonist series have been published for
      GPR139. Two series published by Shi et al. and Dvorak et al. included agonists 1a
      and 7c respectively, with potencies in the ten-nanomolar range. Furthermore,
      Isberg et al. and Liu et al. have previously shown that tryptophan (Trp) and
      phenylalanine (Phe) can activate GPR139 in the hundred-micromolar range. In this
      study, we produced a mutagenesis-guided model of the GPR139 binding site to form
      a foundation for future structure-based ligand optimization. Receptor mutants
      studied in a Ca2+ assay demonstrated that residues F1093*33, H1875*43, W2416*48
      and N2717*38, but not E1083*32, are highly important for the activation of GPR139
      as predicted by the receptor model. The initial ligand-receptor complex was
      optimized through free energy perturbation simulations, generating a refined
      GPR139 model in agreement with experimental data. In summary, the GPR139
      reference surrogate agonists 1a and 7c, and the endogenous amino acids L-Trp and
      L-Phe share a common binding site, as demonstrated by mutagenesis, ligand docking
      and free energy calculations.

PMID- 28442766
TI  - Nanoscale Membrane Domain Formation Driven by Cholesterol.
AB  - Biological membranes generate specific functions through compartmentalized
      regions such as cholesterol-enriched membrane nanodomains that host selected
      proteins. Despite the biological significance of nanodomains, details on their
      structure remain elusive. They cannot be observed via microscopic experimental
      techniques due to their small size, yet there is also a lack of atomistic
      simulation models able to describe spontaneous nanodomain formation in
      sufficiently simple but biologically relevant complex membranes. Here we use
      atomistic simulations to consider a binary mixture of saturated
      dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for
      nanodomain formation. The simulations reveal how cholesterol drives the formation
      of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor
      lipid nanoclusters, both of which show registration between the membrane
      leaflets. The complex nanodomain substructure forms when cholesterol positions
      itself in the domain boundary region. Here cholesterol can also readily flip-flop
      across the membrane. Most importantly, replacing cholesterol with a sterol
      characterized by a less asymmetric ring region impairs the emergence of
      nanodomains. The model considered explains a plethora of controversial
      experimental results and provides an excellent basis for further computational
      studies on nanodomains. Furthermore, the results highlight the role of
      cholesterol as a key player in the modulation of nanodomains for membrane protein
      function.

PMID- 28442767
TI  - Direct, rapid antimicrobial susceptibility test from positive blood cultures
      based on microscopic imaging analysis.
AB  - For the timely treatment of patients with infections in bloodstream and
      cerebrospinal fluid, a rapid antimicrobial susceptibility test (AST) is urgently
      needed. Here, we describe a direct and rapid antimicrobial susceptibility testing
      (dRAST) system, which can determine the antimicrobial susceptibility of bacteria
      from a positive blood culture bottle (PBCB) in six hours. The positive blood
      culture sample is directly mixed with agarose and inoculated into a
      micropatterned plastic microchip with lyophilized antibiotic agents. Using
      microscopic detection of bacterial colony formation in agarose, the total time to
      result from a PBCB for dRAST was only six hours for a wide range of bacterial
      concentrations in PBCBs. The results from the dRAST system were consistent with
      the results from a standard AST, broth microdilution test. In tests of clinical
      isolates (n = 206) composed of 16 Gram-negative species and seven Gram-positive
      species, the dRAST system was accurate compared to the standard broth
      microdilution test, with rates of 91.11% (2613/2868) categorical agreement, 6.69%
      (192/2868) minor error, 2.72% (50/1837) major error and 1.45% (13/896) very major
      error. Thus, the dRAST system can be used to rapidly identify appropriate
      antimicrobial agents for the treatment of blood stream infection (BSI) and
      antibiotic-resistant strain infections.

PMID- 28442768
TI  - Synergistic effect of nitrate-doped TiO2 aerosols on the fast photochemical
      oxidation of formaldehyde.
AB  - The uptake of formaldehyde (HCHO) on mineral dust affects its budget as well as
      particle properties, yet the process has not yet been fully investigate. Here,
      TiO2 and nitrate-doped TiO2 aerosols were used as proxies for mineral dust, and
      the uptake of HCHO was explored in a chamber under both dark and illuminated
      conditions. The uptake loss of HCHO on UV-illuminated aerosols is 2-9 times
      faster than its gaseous photolysis in our experimental system. The uptake
      coefficient in the range of 0.43-1.68 * 10-7 is 1-2 orders of magnitude higher
      than previous reports on model mineral dust particles. The reaction rate exhibits
      a Langmuir-Hinshelwood-type dependence on nitrate content and relative humidity,
      suggesting the competitive role of nitrate salts, water vapor and HCHO on the
      TiO2 surface. The reaction produces carbon dioxide as the main product and
      gaseous formic acid as an important intermediate. The hydroxyl radical produced
      on illuminated TiO2 primarily drives the fast oxidation of HCHO. The nitrate
      radical arising from the TiO2-catalyzed photoreaction of nitrate synergistically
      promotes the oxidation process. This study suggests a novel oxidation route for
      HCHO in the atmosphere, taking into account high abundance of both mineral dust
      and anthropogenic TiO2 aerosols.

PMID- 28442769
TI  - Improved phylogenetic resolution for Y-chromosome Haplogroup O2a1c-002611.
AB  - Y-chromosome Haplogroup O2a1c-002611 is one of the dominant lineages of East
      Asians and Southeast Asians. However, its internal phylogeny remains
      insufficiently investigated. In this study, we genotyped 89 new highly
      informative single nucleotide polymorphisms (SNPs) in 305 individuals with
      Haplogroup O2a1c-002611 identified from 2139 Han Chinese males. Two major
      branches were identified, O2a1c1-F18 and O2a1c2-L133.2 and the first was further
      divided into two main subclades, O2a1c1a-F11 and O2a1c1b-F449, accounting for
      11.13% and 2.20% of Han Chinese, respectively. In Haplogroup O2a1c1a-F11, we also
      determined seven sublineages with quite different frequency distributions in Han
      Chinese ranging from 0.187% to 3.553%, implying they might have different
      demographic history. The reconstructed haplogroup tree for all the major clades
      within Haplogroup O2a1c-002611 permits better resolution of male lineages in
      population studies of East Asia and Southeast Asia. The dataset generated in the
      present study are also valuable for forensic identification and paternity tests
      in China.

PMID- 28442770
TI  - Design principles governing chemomechanical coupling of kinesin.
AB  - A systematic chemomechanical network model for the molecular motor kinesin is
      presented in this report. The network model is based on the nucleotide-dependent
      binding affinity of the heads to an microtubule (MT) and the asymmetries and
      similarities between the chemical transitions caused by the intramolecular strain
      between the front and rear heads. The network model allows for multiple
      chemomechanical cycles and takes into account all possible mechanical transitions
      between states in which one head is strongly bound and the other head is weakly
      bound to an MT. The results obtained from the model show the ATP-concentration
      dependence of the dominant forward stepping cycle and support a gated rear head
      mechanism in which the forward step is controlled by ATP hydrolysis and the
      resulting ADP-bound state of the rear head when the ATP level is saturated. When
      the ATP level is saturated, the energy from ATP hydrolysis is used to concentrate
      the chemical transition flux to a force-generating state that can produce the
      power stroke. In contrast, when the ATP level is low, the hydrolysis energy is
      consumed to avoid states in which the leading head is weakly bound to an MT and
      to inhibit frequent backward steps upon loading.

PMID- 28442771
TI  - Double-stranded DNA induces a prothrombotic phenotype in the vascular
      endothelium.
AB  - Double-stranded DNA (dsDNA) constitutes a potent activator of innate immunity,
      given its ability to bind intracellular pattern recognition receptors during
      viral infections or sterile tissue damage. While effects of dsDNA in immune cells
      have been extensively studied, dsDNA signalling and its pathophysiological
      implications in non-immune cells, such as the vascular endothelium, remain poorly
      understood. The aim of this study was to characterize prothrombotic effects of
      dsDNA in vascular endothelial cells. Transfection of cultured human endothelial
      cells with the synthetic dsDNA poly(dA:dT) induced upregulation of the
      prothrombotic molecules tissue factor and PAI-1, resulting in accelerated blood
      clotting in vitro, which was partly dependent on RIG-I signalling. Prothrombotic
      effects were also observed upon transfection of endothelial cells with hepatitis
      B virus DNA-containing immunoprecipitates as well human genomic DNA. In addition,
      dsDNA led to surface expression of von Willebrand factor resulting in increased
      platelet-endothelium-interactions under flow. Eventually, intrascrotal injection
      of dsDNA resulted in accelerated thrombus formation upon light/dye-induced
      endothelial injury in mouse cremaster arterioles and venules in vivo. In
      conclusion, we show that viral or endogenous dsDNA induces a prothrombotic
      phenotype in the vascular endothelium. These findings represent a novel link
      between pathogen- and danger-associated patterns within innate immunity and
      thrombosis.

PMID- 28442772
TI  - Discriminative and Distinct Phenotyping by Constrained Tensor Factorization.
AB  - Adoption of Electronic Health Record (EHR) systems has led to collection of
      massive healthcare data, which creates oppor- tunities and challenges to study
      them. Computational phenotyping offers a promising way to convert the sparse and
      complex data into meaningful concepts that are interpretable to healthcare givers
      to make use of them. We propose a novel su- pervised nonnegative tensor
      factorization methodology that derives discriminative and distinct phenotypes. We
      represented co-occurrence of diagnoses and prescriptions in EHRs as a third-order
      tensor, and decomposed it using the CP algorithm. We evaluated discriminative
      power of our models with an Intensive Care Unit database (MIMIC-III) and
      demonstrated superior performance than state-of-the-art ICU mortality calculators
      (e.g., APACHE II, SAPS II). Example of the resulted phenotypes are sepsis with
      acute kidney injury, cardiac surgery, anemia, respiratory failure, heart failure,
      cardiac arrest, metastatic cancer (requiring ICU), end-stage dementia (requiring
      ICU and transitioned to comfort-care), intraabdominal conditions, and alcohol
      abuse/withdrawal.

PMID- 28442773
TI  - Efficacy of Recent Emissions Controls on Road Vehicles in Europe and Implications
      for Public Health.
AB  - Road traffic is a major source of urban air pollution responsible for substantial
      premature mortality. Until recently, attention has focussed primarily on exhaust
      emissions of particulate matter from traffic as a causal factor. From analysis of
      air quality measurement data from the UK and France, we demonstrate that road
      traffic exhaust has a far greater impact on concentrations of nitrogen dioxide
      than of PM2.5. PM2.5 and carbonaceous particle concentrations have been declining
      appreciably since 2010/11 due to the use of diesel particle filters, but little
      change is seen in nitrogen dioxide over the period from 1995 to 2015. It is shown
      that the effect of NO2 from road traffic upon premature mortality was ten-fold
      greater than that of PM2.5 even before the widespread use of diesel particle
      filters, and is now considerably larger. The overwhelming contribution of diesel
      compared to gasoline-fuelled vehicles to emissions of both PM2.5 and NO2
      emphasises the importance of further controls on emissions from diesels.

PMID- 28442774
TI  - Designed synthesis of a "One for Two" hydrophilic magnetic amino-functionalized
      metal-organic framework for highly efficient enrichment of glycopeptides and
      phosphopeptides.
AB  - Highly efficient enrichment of glycopeptides or phosphopeptides from complex
      biological samples is indispensable for high-throughput mass spectrometry
      analysis. In this study, for the first time, a "one for two" hydrophilic magnetic
      amino-functionalized metal-organic framework (MOF) was designed and synthesized
      for selective enrichment of both glycopeptides and phosphopeptides. A well-known
      solvo-thermal reaction was adopted to prepare a magnetic core Fe3O4, followed by
      self- polymerization of dopamine, creating a polydopamine (PDA) onto Fe3O4.
      Thanks to the hydroxyl and amino group of PDA, Zr3+ was easily adhered to the
      surface, inducing the following one-pot MOF reaction with amino ligand. After
      characterization of the as-prepared MOFs (denoted as Fe3O4@PDA@UiO-66-NH2), its
      ultrahigh surface area, excellent hydrophilicity and strong magnetic
      responsiveness were highly confirmed. Based on hydrophilic interaction, it was
      applied to glycopeptide enrichment, while based on strong binding between Zr and
      phosphopeptides, it was applied to phosphopeptide enrichment, both exhibiting
      excellent performance in standard proteins and human serum with high sensitivity
      and selectivity. These results showed the as-prepared MOFs had great potential in
      proteomics research.

PMID- 28442775
TI  - Deterministic Bragg Coherent Diffraction Imaging.
AB  - A deterministic variant of Bragg Coherent Diffraction Imaging is introduced in
      its kinematical approximation, for X-ray scattering from an imperfect crystal
      whose imperfections span no more than half of the volume of the crystal. This
      approach provides a unique analytical reconstruction of the object's structure
      factor and displacement fields from the 3D diffracted intensity distribution
      centred around any particular reciprocal lattice vector. The simple closed-form
      reconstruction algorithm, which requires only one multiplication and one Fourier
      transformation, is not restricted by assumptions of smallness of the displacement
      field. The algorithm performs well in simulations incorporating a variety of
      conditions, including both realistic levels of noise and departures from ideality
      in the reference (i.e. imperfection-free) part of the crystal.

PMID- 28442776
TI  - miR-301b~miR-130b-PPARgamma axis underlies the adipogenic capacity of mesenchymal
      stem cells with different tissue origins.
AB  - Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and
      cellular therapy due to their multi-lineage differentiation potential and
      immunomodulatory function. The applicability of MSCs also depends on their
      cellular sources and in vivo functions. Here in this study, we systematically
      compared the morphologic characteristics, immunophenotypes and the adipogenic
      differentiation of MSCs derived from umbilical cord (UC), adipose tissue (Ad) and
      bone marrow (BM). We found that the three tissues-derived MSCs displayed
      decreased adipogenic capacity in the order: Ad-MSC > BM-MSC > UC-MSC, and no
      morphologic and immunophenotypic differences were observed. Mechanistic
      investigation revealed a miR-301b~miR-130b-PPARgamma axis, whose expression
      pattern in UC-MSC, Ad-MSC and BM-MSC significantly correlates with their
      adipogenic capacity. Our results come up with a potential mechanism to elucidate
      the differential adipogenesis of Ad-MSC, BM-MSC and UC-MSC, which would provide
      instructional advice for which source of MSCs to choose according to a certain
      clinical purpose. Furthermore, the miR-301b~miR-130b-PPARgamma axis may also be
      used as a potential therapeutic target for the disorders associated with MSCs
      mediated abnormal adipogenesis.

PMID- 28442779
TI  - On food supply and obesity, missing the point is easy.

PMID- 28442777
TI  - Serotonin transporter deficiency drives estrogen-dependent obesity and glucose
      intolerance.
AB  - Depression and use of antidepressant medications are both associated with
      increased risk of obesity, potentially attributed to a reduced serotonin
      transporter (SERT) function. However, how SERT deficiency promotes obesity is
      unknown. Here, we demonstrated that SERT -/- mice display abnormal fat
      accumulation in both white and brown adipose tissues, glucose intolerance and
      insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and
      reduced circulating 17beta-estradiol levels. 17beta-estradiol replacement in SERT
      -/- mice reversed the obesity and glucose intolerance, supporting a role for
      estrogen in SERT deficiency-associated obesity and glucose intolerance. Treatment
      of wild type mice with paroxetine, a chemical inhibitor of SERT, also resulted in
      Cyp19a1 suppression, decreased circulating 17beta-estradiol levels, abnormal fat
      accumulation, and glucose intolerance. Such effects were not observed in
      paroxetine-treated SERT -/- mice. Conversely, pregnant SERT -/- mice displayed
      normalized estrogen levels, markedly reduced fat accumulation, and improved
      glucose tolerance, which can be eliminated by an antagonist of estrogen receptor
      alpha (ERalpha). Together, these findings support that estrogen suppression is
      involved in SERT deficiency-induced obesity and glucose intolerance, and suggest
      approaches to restore 17beta-estradiol levels as a novel treatment option for
      SERT deficiency associated obesity and metabolic abnormalities.

PMID- 28442778
TI  - As a carrier-transporter for hair follicle reconstitution, platelet-rich plasma
      promotes proliferation and induction of mouse dermal papilla cells.
AB  - Morphogenesis of hair follicles during development and in hair reconstitution
      assays involves complex interactions between epithelial cells and dermal papilla
      cells (DPCs). DPCs may be a source of cells for hair regeneration in alopecia
      patients. Reconstitution of engineered hair follicles requires in vitro culture
      of trichogenic cells, a three-dimensional scaffolds, and biomolecular signals.
      However, DPCs tend to lose their biological activity when cultured as trichogenic
      cells, and scaffolds currently used for hair follicle regeneration lack
      biological efficiency and biocompatibility. Platelet-rich plasma (PRP) gel forms
      a three-dimensional scaffold that can release endogenous growth factors, is
      mitogenic for a variety of cell types and is used in model tissue repair and
      regeneration systems. We found that 5% activated PRP significantly enhanced cell
      proliferation and hair-inductive capability of mouse and human DPCs in vitro and
      promoted mouse hair follicle formation in vivo. PRP also formed a three
      dimensional gel after activation. We used PRP gel as a scaffold to form many de
      novo hair follicles on a plane surface, showing it to be candidate bioactive
      scaffold capable of releasing endogenous growth factors for cell-based hair
      follicle regeneration.

PMID- 28442780
TI  - The effect of body composition and serum inflammatory markers on the functional
      muscle-bone unit in premenopausal women.
AB  - BACKGROUND/OBJECTIVES: A number of recent studies dealing with the relationship
      between the effects of high body mass (BM) and fat mass (FM) on bone mass and
      strength exhibit a range of contrasting variations in their findings. These
      diverse findings have led to an ongoing controversy as to whether high BM and FM
      positively or negatively affect bone mass and strength. Excessive FM and the
      associated low-grade inflammation might overturn the higher mechanical stimulus
      arising from a higher BM. Therefore, we aimed at quantifying the functional
      muscle-bone unit in premenopausal women with markedly diverging body composition.
      SUBJECTS/METHODS: Sixty-four young women with BMs ranging from 50 to 113 kg and
      body fat percentages between 20.7% and 51.8% underwent jumping mechanography and
      peripheral quantitative computed tomography measurements. Maximum voluntary
      ground reaction force during multiple one-legged hopping (Fm1LH), as well as bone
      characteristics at 4, 14 and 38% of tibia length, were determined. Body
      composition was assessed by dual-energy X-ray absorptiometry, and serum
      inflammatory markers were analyzed from blood samples. RESULTS: Fm1LH predicted
      volumetric bone mineral content at the 14% site by 48.7%. Women with high body
      fat percentage had significantly higher Fm1LH, significantly lower relative bone
      mass, relative bone strength and relative bone area, as well as higher serum
      inflammatory markers in comparison to women with lower body fat percentage.
      CONCLUSIONS: In conclusion, high body fat percentage was associated with lower
      relative bone mass and strength despite normal habitual muscle force in
      premenopausal women, indicating that high body fat percentage compromised the
      functional muscle-bone unit in these individuals.

PMID- 28442782
TI  - Gut microbiota - at the intersection of everything?
AB  - Over the past decade, numerous studies have found an association between the gut
      microbiota composition and many diseases. However, is it reality? Or is the truth
      hidden in the shadow of several thousand publications a year with inflated
      expectations in almost any disease?

PMID- 28442783
TI  - FROM AACR 2017.

PMID- 28442781
TI  - Spreading depolarization remarkably exacerbates ischemia-induced tissue acidosis
      in the young and aged rat brain.
AB  - Spreading depolarizations (SDs) occur spontaneously in the cerebral cortex of
      subarachnoid hemorrhage, stroke or traumatic brain injury patients. Accumulating
      evidence prove that SDs exacerbate focal ischemic injury by converting zones of
      the viable but non-functional ischemic penumbra to the core region beyond rescue.
      Yet the SD-related mechanisms to mediate neurodegeneration remain poorly
      understood. Here we show in the cerebral cortex of isoflurane-anesthetized, young
      and old laboratory rats, that SDs propagating under ischemic penumbra-like
      conditions decrease intra and- extracellular tissue pH transiently to levels,
      which have been recognized to cause tissue damage. Further, tissue pH after the
      passage of each spontaneous SD event remains acidic for over 10 minutes. Finally,
      the recovery from SD-related tissue acidosis is hampered further by age. We
      propose that accumulating acid load is an effective mechanism for SD to cause
      delayed cell death in the ischemic nervous tissue, particularly in the aged
      brain.

PMID- 28442784
TI  - The RNA-binding protein MARF1 promotes cortical neurogenesis through its RNase
      activity domain.
AB  - Cortical neurogenesis is a fundamental process of brain development that is
      spatiotemporally regulated by both intrinsic and extrinsic cues. Although recent
      evidence has highlighted the significance of transcription factors in cortical
      neurogenesis, little is known regarding the role of RNA-binding proteins (RBPs)
      in the post-transcriptional regulation of cortical neurogenesis. Here, we report
      that meiosis arrest female 1 (MARF1) is an RBP that is expressed during neuronal
      differentiation. Cortical neurons expressed the somatic form of MARF1 (sMARF1)
      but not the oocyte form (oMARF1). sMARF1 was enriched in embryonic brains, and
      its expression level decreased as brain development progressed. Overexpression of
      sMARF1 in E12.5 neuronal progenitor cells promoted neuronal differentiation,
      whereas sMARF1 knockdown decreased neuronal progenitor differentiation in vitro.
      We also examined the function of sMARF1 in vivo using an in utero electroporation
      technique. Overexpression of sMARF1 increased neuronal differentiation, whereas
      knockdown of sMARF1 inhibited differentiation in vivo. Moreover, using an RNase
      domain deletion mutant of sMARF1, we showed that the RNase domain is required for
      the effects of sMARF1 on cortical neurogenesis in vitro. Our results further
      elucidate the mechanisms of post-transcriptional regulation of cortical
      neurogenesis by RBPs.

PMID- 28442785
TI  - Hunter-Gatherer Social Networks and Reproductive Success.
AB  - Individuals' centrality in their social network (who they and their social ties
      are connected to) has been associated with fertility, longevity, disease and
      information transmission in a range of taxa. Here, we present the first
      exploration in humans of the relationship between reproductive success and
      different measures of network centrality of 39 Agta and 38 BaYaka mothers. We
      collected three-meter contact ('proximity') networks and reproductive histories
      to test the prediction that individual centrality is positively associated with
      reproductive fitness (number of living offspring). Rather than direct social ties
      influencing reproductive success, mothers with greater indirect centrality (i.e.
      centrality determined by second and third degree ties) produced significantly
      more living offspring. However, indirect centrality is also correlated with
      sickness in the Agta, suggesting a trade-off. In complex social species, the
      optimisation of individuals' network position has important ramifications for
      fitness, potentially due to easy access to different parts of the network,
      facilitating cooperation and social influence in unpredictable ecologies.

PMID- 28442786
TI  - MicroRNA-30a Regulation of Epithelial-Mesenchymal Transition in Diabetic
      Cataracts Through Targeting SNAI1.
AB  - Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental
      process in development, fibrosis, and metastasis. During the process, epithelial
      cells lose their morphology and transcriptional program, and transdifferentiate
      to mesenchymal cells. It has been reported that lens epithelial cells undergo EMT
      during cataract formation, and regulation of microRNAs on genes is associated
      with lens development. However, the molecular mechanisms of this regulation in
      diabetic cataract still need to be investigated. In the present study, the
      expression of E-cadherin was downregulated, while the expression of alpha-SMA and
      vimentin was upregulated in diabetic cataract tissues and the in vitro model,
      suggesting the involvement of EMT in diabetic cataract formation. Results of
      miRNA profiling demonstrated that miR-30a was markedly downregulated in diabetic
      cataract tissues. Overexpression of miR-30a-5p decreased SNAI1, a known modulator
      of EMT, and the expression of vimentin and alpha-SMA in our diabetic cataract
      model in vitro. It is concluded that EMT is involved in human diabetic cataract,
      and upregulation of miR-30a can repress EMT through its targeting of SNAI1 in
      lens epithelial cells, which make miR-30a a novel target of therapeutic
      intervention for human diabetic cataract.

PMID- 28442787
TI  - The upper limit of the in-plane spin splitting of Gaussian beam reflected from a
      glass-air interface.
AB  - Optical spin splitting has a promising prospect in quantum information and
      precision metrology. Since it is typically small, many efforts have been devoted
      to its enhancement. However, the upper limit of optical spin splitting remains
      uninvestigated. Here, we investigate systematically the in-plane spin splitting
      of a Gaussian beam reflected from a glass-air interface and find that the spin
      splitting can be enhanced in three different incident angular ranges: around the
      Brewster angle, slightly smaller than and larger than the critical angle for
      total reflection. Within the first angular range, the reflected beam can undergo
      giant spin splitting but suffers from low energy reflectivity. In the second
      range, however, a large spin splitting and high energy reflectivity can be
      achieved simultaneously. The spin splitting becomes asymmetrical within the last
      angular range, and the displacement of one spin component can be up to half of
      incident beam waist w 0/2. Of all the incident angles, the spin splitting reaches
      its maximum at Brewster angle. This maximum splitting increases with the
      refractive index of the "glass" prism, eventually approaching an upper limit of w
      0. These findings provide a deeper insight into the optical spin splitting
      phenomena and thereby facilitate the development of spin-based applications.

PMID- 28442788
TI  - Changes in structural and pigmentary colours in response to cold stress in
      Polyommatus icarus butterflies.
AB  - While numerous papers have investigated the effects of thermal stress on the
      pigmentary colours of butterfly wings, such studies regarding structural colours
      are mostly lacking, despite the important role they play in sexual communication.
      To gain insight into the possible differences between the responses of the two
      kinds of colouration, we investigated the effects of prolonged cold stress
      (cooling at 5  degrees C for up to 62 days) on the pupae of Polyommatus icarus
      butterflies. The wing surfaces coloured by photonic crystal-type
      nanoarchitectures (dorsal) and by pigments (ventral) showed markedly different
      behaviours. The ventral wing surfaces exhibited stress responses proportional in
      magnitude to the duration of cooling and showed the same trend for all
      individuals, irrespective of their sex. On the dorsal wing surface of the males,
      with blue structural colouration, a smaller magnitude response was found with
      much more pronounced individual variations, possibly revealing hidden genetic
      variations. Despite the typical, pigmented brown colour of the dorsal wing
      surface of the females, all cooled females exhibited a certain degree of blue
      colouration. UV-VIS spectroscopy, optical microscopy, and scanning and
      transmission electron microscopy were used to evaluate the magnitude and
      character of the changes induced by the prolonged cold stress.

PMID- 28442789
TI  - Elastic turbulence in entangled semi-dilute DNA solutions measured with optical
      coherence tomography velocimetry.
AB  - The flow instabilities of solutions of high molecular weight DNA in the entangled
      semi-dilute concentration regime were investigated using optical coherence
      tomography velocimetry, a technique that provides high spatial (probe volumes of
      3.4 pL) and temporal resolution (sub MUs) information on the flow behaviour of
      complex fluids in a rheometer. The velocity profiles of the opaque DNA solutions
      (high and low salt) were measured as a function of the distance across the gap of
      a parallel plate rheometer, and their evolution over time was measured. At lower
      DNA concentrations and low shear rates, the velocity fluctuations were well
      described by Gaussian functions and the velocity gradient was uniform across the
      rheometer gap, which is expected for Newtonian flows. As the DNA concentration
      and shear rate were increased there was a stable wall slip regime followed by an
      evolving wall slip regime, which is finally followed by the onset of elastic
      turbulence. Strain localization (shear banding) is observed on the boundaries of
      the flows at intermediate shear rates, but decreases in the high shear elastic
      turbulence regime, where bulk strain localization occurs. A dynamic phase diagram
      for non-linear flow was created to describe the different behaviours.

PMID- 28442791
TI  - Vortex dynamics and frequency splitting in vertically coupled nanomagnets.
AB  - We explored the dynamic response of a vortex core in a circular nanomagnet by
      manipulating its dipole-dipole interaction with another vortex core confined
      locally on top of the nanomagnet. A clear frequency splitting is observed
      corresponding to the gyrofrequencies of the two vortex cores. The peak positions
      of the two resonance frequencies can be engineered by controlling the magnitude
      and direction of the external magnetic field. Both experimental and micromagnetic
      simulations show that the frequency spectra for the combined system is
      significantly dependent on the chirality of the circular nanomagnet and is
      asymmetric with respect to the external bias field. We attribute this result to
      the strong dynamic dipole-dipole interaction between the two vortex cores, which
      varies with the distance between them. The possibility of having multiple states
      in a single nanomagnet with vertical coupling could be of interest for
      magnetoresistive memories.

PMID- 28442790
TI  - Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental
      fatigue of Parkinson disease.
AB  - Fatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It
      included physical fatigue and mental fatigue. The potential mechanisms of mental
      fatigue involving serotonergic dysfunction and abnormal iron metabolism are still
      unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients
      into fatigue group and non-fatigue group, and detected the levels of serotonin,
      iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly
      decreased and the levels of iron and transferrin are dramatically increased in
      fatigue group. In fatigue group, mental fatigue score is negatively correlated
      with 5-HT level in CSF, and positively correlated with the scores of depression
      and excessive daytime sleepiness, and disease duration, also, mental fatigue is
      positively correlated with the levels of iron and transferrin in CSF. Transferrin
      level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5
      HT and transferrin are markedly decreased in fatigue group; mental fatigue score
      exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in
      both central and peripheral systems may be correlated with mental fatigue through
      abnormal iron metabolism. Depression, excessive daytime sleepiness and disease
      duration were the risk factors for mental fatigue of PD.

PMID- 28442792
TI  - A SMARCD2-containing mSWI/SNF complex is required for granulopoiesis.
AB  - Mammalian SWI/SNF complexes have critical roles in development and
      differentiation, and are implicated in the pathogenesis of several diseases;
      however, the mechanisms underpinning disease manifestation and the specificity of
      the subunits mutated are incompletely understood. Newly identified loss-of
      function mutations in the SMARCD2 gene (part of the SMARCD1, SMARCD2 and SMARCD3
      paralog family) reveal an evolutionarily conserved role specifically for the
      SMARCD2 subunit in granulopoiesis, and further investigation implicates the CEBPE
      transcription factor as a key effector of this specific function.

PMID- 28442793
TI  - The future of human genome editing.

PMID- 28442794
TI  - Innate and adaptive immunity shape circulating HCV strains.
AB  - An unbiased genome-to-genome analysis in chronic hepatitis C virus (HCV)
      infection confirms the innate and adaptive arms of the immune system as drivers
      of viral evolution. Viral adaptation has a critical role in the interaction
      between host and pathogen and has important clinical implications for infection
      outcome.

PMID- 28442795
TI  - Becoming weeds.
AB  - A new resequencing analysis of weedy rice (Oryza sativa L.) biotypes illuminates
      distinct evolutionary paths and outcomes of de-domestication and ferality. This
      largest effort to date in weedy plant genomics gives a better understanding of
      weediness while also providing a promising source of alleles for rice breeding.

PMID- 28442796
TI  - Resonant Raman scattering based approaches for the quantitative assessment of
      nanometric ZnMgO layers in high efficiency chalcogenide solar cells.
AB  - This work reports a detailed resonant Raman scattering analysis of ZnMgO solid
      solution nanometric layers that are being developed for high efficiency
      chalcogenide solar cells. This includes layers with thicknesses below 100 nm and
      compositions corresponding to Zn/(Zn + Mg) content rations in the range between
      0% and 30%. The vibrational characterization of the layers grown with different
      compositions and thicknesses has allowed deepening in the knowledge of the
      sensitivity of the different Raman spectral features on the characteristics of
      the layers, corroborating the viability of resonant Raman scattering based
      techniques for their non-destructive quantitative assessment. This has included a
      deeper analysis of different experimental approaches for the quantitative
      assessment of the layer thickness, based on (a) the analysis of the intensity of
      the ZnMgO main Raman peak; (b) the evaluation of the changes of the intensity of
      the main Raman peak from the subjacent layer located below the ZnMgO one; and (c)
      the study of the changes in the relative intensity of the first to second/third
      order ZnMgO peaks. In all these cases, the implications related to the presence
      of quantum confinement effects in the nanocrystalline layers grown with different
      thicknesses have been discussed and evaluated.

PMID- 28442797
TI  - Pre- and post-sexual exposure prophylaxis of HIV: An update.
AB  - Pitfalls in current HIV prevention strategies include late HIV testing,
      vulnerability among youth and females; lack of emphasis on treatment, low
      acceptance of circumcision, and nonavailability of protective vaccines.
      Continuing high-risk sexual behavior, forceful sex, coercive and nonconsensual
      sex, rape, and unprotected sexual activities make women the most vulnerable to
      acquisition of sexually transmitted infection/HIV and necessitates a more radical
      approach of prevention in high-risk individuals who do not have HIV. Preexposure
      prophylaxis is defined as the administration of antiretroviral drugs to an
      uninfected person before potential HIV exposure to reduce the risk of infection
      and continued during risk. The rationale of this approach is to administer
      preventive dose of drug(s) before exposure to HIV so the moment virus enters the
      body, HIV replication is inhibited and HIV is not able to establish permanent
      infection. Postexposure prophylaxis (PEP) following potential sexual exposure is
      an important form of nonoccupational PEP which is an emergency intervention to
      abort HIV acquisition arising from exposure to HIV-infected blood or potentially
      infectious bodily fluids following sexual exposure.

PMID- 28442798
TI  - Knowledge and attitude about sexually transmitted infections other than HIV among
      college students.
AB  - BACKGROUND: Sexually transmitted infections (STIs) are the infections which are
      mainly transmitted through sexual intercourse. Young individuals in the age group
      of 16 to 24 years are considered to be at more risk for STIs compared to older
      adults. Young individuals are more likely to practice unprotected sex and have
      multiple sexual partners. If the STIs are not treated adequately, it can lead to
      various complications.Most of the people may be aware about HIV/AIDs because of
      the awareness created by media and the government programs, however knowledge
      about STIs other than HIV/AIDS is low in the developing countries. MATERIALS AND
      METHODS: This study was a descriptive cross sectional study to assess the
      knowledge, awareness and attitude of college students about STIs other than HIV.
      A total of 350 engineering students from various semesters were included in the
      study. They were asked to fill up an anonymous questionnaire. RESULTS: Two
      hundred and fifty six (73%) males and 94 (27%) females participated in the study.
      313 (90%) students had heard about sexually transmitted infections (STIs) and 223
      (64%) students had heard about STIs other than HIV. 99% of students knew about
      HIV where as less than 50% of students knew about other STIs. Teachers, internet
      and media were the source of information for most of the participants. Almost 75%
      of the students knew about the modes of transmission of STIs. Less than 50% of
      the participants knew about the symptoms of STIs and complications. Also attitude
      of the students towards sexual health and prevention of STIs was variable.
      CONCLUSION: The findings of our study shows that it is important to orient the
      students about sexual health and safe sexual practices as it will go a long way
      in prevention and control of STIs. Also the morbidities and complications
      associated with STIs can be prevented.

PMID- 28442799
TI  - Study of pruritus vulvae in geriatric age group in tertiary hospital.
AB  - BACKGROUND: According to the World Health Organization criteria, geriatric
      population is people above 60 years of age. In this phase of life, a woman has
      already gone through menopause and its associated emotional, physical, and
      hormonal changes. These changes are due to gradual loss of estrogen that comes
      with menopause which results in dramatic changes in the appearance of vulva and
      vagina. With age, skin of vulva becomes thin, loses elasticity, and moisture so
      that the patient starts feeling burning and itchy sensation. The normal acidic pH
      changes to basic which alters the flora and makes the person prone to other
      bacterial infections. Apart from infections, there are many other dermatological
      and nondermatological causes of vulvar itching in this age group such as eczema,
      contact dermatitis, lichen planus (LP), lichen sclerosus atrophicans, lichen
      simplex chronicus (LSC), prolapse, incontinence, and carcinoma. The aim is to
      diagnose the causes of pruritus vulvae in the geriatric age group to decrease the
      misery of these patients. METHODS: We selected 40 consecutive females of age
      group ranging from 60 to 75 years coming to skin OPD with the complaint of
      pruritus of vulvar region over a period of 1 year. Clinical examination, complete
      blood count, fasting blood sugar, wet mount, pap smear, and skin biopsy were done
      in every case. RESULTS: Out of the forty patients who were included in this
      study, 17 (42.5%) were diagnosed as a case of LSC and 11 (27.5%) patients had
      atrophic vaginitis. Three (7.5%) patients presented with tinea. Three (7.5%)
      cases were clinically diagnosed as scabies. Another 2 (5%) cases were diagnosed
      as LP and Candida was seen in other 2 (5%) cases. 1 (2.5%) case was diagnosed as
      bacillary vaginosis and 1 (2.5%) patient was of lichen sclerosus. CONCLUSION:
      Pruritus vulvae of geriatric age group are of diverse etiology, therefore,
      treatment based on precise diagnosis is of prime importance.

PMID- 28442800
TI  - What puts them at risk? A cross-sectional case-control survey of demographic
      profile and sexual behavior of patients with sexually transmitted infections at a
      tertiary care center in North India.
AB  - BACKGROUND: Sexually transmitted infections (STIs) are a major public health
      problem in developing nations. Identification of risk factors can help in
      formulating effective strategies against them. The present study was conducted in
      a tertiary care hospital in North India over 1 year to identify the risk factors
      associated with STIs. MATERIALS AND METHODS: A questionnaire-based cross
      sectional case-control survey was conducted where participants answered questions
      on demographic details, sexual behavior, and awareness of STIs. Cases were
      patients with STIs whereas controls were randomly selected from healthy
      individuals accompanying patients with nonvenereal complaints attending our
      hospital. RESULTS: There were 106 cases and 64 controls. STI patients had sexual
      debut 2 years before controls. A higher proportion of STI cases had lower
      education, multiple sexual partners, lived separately from their partner, had
      nonregular partners, had protected sex in the last month, had sex under influence
      of alcohol/illicit drugs, sex in unstructured settings, and engaged in
      transactional sex, in comparison to controls (P < 0.05). More cases were aware of
      the symptoms/preventive measures of STIs (P < 0.001). On multivariate analysis,
      multiple sexual partners, sex under influence of alcohol/illicit drugs with
      nonregular partner, protected sex in the last month, and knowledge of preventive
      measures were found to be statistically associated with STIs (P < 0.05).
      CONCLUSIONS: Our study identifies risk-behavior patterns in patients with STIs,
      which should be modified to reduce the burden of these diseases. Increasing the
      knowledge about STIs in these patients can translate into more common condom
      usage that lends support for strengthening sexual health programs at grass-root
      levels. LIMITATIONS: The small size of the study population could have led to
      decreased power of the study to detect differences between cases and controls.
      The external validity of our results needs to be tested in different population
      groups involving larger sample sizes.

PMID- 28442801
TI  - Treatment outcomes and loss to follow-up rate of male patients with gonococcal
      and nongonococcal urethritis who attended the sexually transmitted disease
      clinic: An 8-year retrospective study.
AB  - BACKGROUND: Poor follow-up compliance of patients with infectious urethritis is a
      recognized and serious public health problem in Thailand. AIM: The aim of this
      study was to determine treatment outcomes and loss to follow-up rate of male
      patients with gonococcal urethritis (GU) and non-GU (NGU) at a sexually
      transmitted disease (STD) clinic at Thailand's tertiary hospital. METHODS: This
      retrospective chart review of male patients who sought treatment at STDs Clinic,
      Siriraj Hospital, and who were diagnosed with GU and/or NGU was conducted during
      January 2007 to December 2014 study period. RESULTS: Two hundred and twenty-seven
      male urethritis patients were included in this study with a mean age was 29.5
      years. GU and NGU were found in 120 (52.9%) and 107 (47.1%) of patients,
      respectively. Overall prevalence of GU and NGU during the 8-year study period at
      STD Clinic, Siriraj Hospital, was 8.6% and 7.8%, respectively. Ninety-six
      patients (42.3%) were lost to follow-up. Recurrent urethritis was found in 23.8%
      of patients, and HIV infection was identified in 11.6%. Mean age of patients lost
      to follow-up was 29 years. Compared with patients who attended every scheduled
      follow-up visit, men who have sex with men had a significantly lower rate of loss
      to follow-up (P = 0.012). CONCLUSION: Almost half of patients with GU or NGU were
      lost to follow-up, and one-quarter had recurrent urethritis. Fast and easy access
      to services that provide accurate diagnostic testing and effective treatment
      should be a public health priority to prevent complications and reduce rates of
      disease transmission.

PMID- 28442802
TI  - Study of prevalence of sexually transmitted infections/human immunodeficiency
      virus and condom use among male-to-female transgender: A retrospective analysis
      from a tertiary care hospital in Chennai.
AB  - CONTEXT: A "Transgender" person is one who dresses as, desires to be, has
      undergone surgery to become or identifies with opposite sex. They have a higher
      risk of sexually transmitted infection (STI) due to a combination of biological
      and social reasons. They have risky sexual behaviors but low-risk perception.
      AIMS: The aim of this study is to determine the prevalence of STI/human
      immunodeficiency virus (HIV) in transgender (TG) and association with condom use.
      SETTINGS AND DESIGN: A retrospective study of 82 male-to-female TGs attending our
      sexually transmitted disease (STD) clinic from 2011 to 2014 was undertaken.
      SUBJECTS AND METHODS: Detailed history including sexual exposure, high-risk
      practices, and condom usage was obtained, and clinical examination for any
      evidence of STI was done. They were screened for the presence of STI/HIV and
      other appropriate investigations were done whenever required. STATISTICAL
      ANALYSIS USED: Retrospective analysis was used. RESULTS: In our study, the total
      prevalence of STI/HIV in the studied population was 48.8% which was considerably
      higher than the prevalence in the general population which was 5.4%. Promiscuity
      rate of TGs studied was 45%, 33% of them were male sex workers. Syphilis was the
      most common STD, followed by HIV, genital warts, and gonorrhea. The prevalence of
      condom use was 45.1%, and the prevalence of STI/HIV in the condom used TGs was
      14.6%. CONCLUSION: Based on the above findings, the TG group is found to have a
      higher prevalence of HIV/STI despite the higher use of condoms which is mostly
      attributable to the lack of correct and consistent use of condoms. This stresses
      upon the importance of promoting the condom usage and knowledge, and also this
      group should be the focus of intensive intervention programs aimed at STI
      screening and treatment, reduction of risky sexual behavior, and promotion of HIV
      counseling and testing.

PMID- 28442804
TI  - Clinico-epidemiological profile of patients attending Suraksha Clinic of tertiary
      care hospital of North India.
AB  - BACKGROUND: Sexually transmitted infections (STIs) are a global health problem.
      Trends of STIs vary from place to place depending on various epidemiological
      factors prevailing in that respective geographic area. AIMS AND OBJECTIVES: The
      present study was conducted to find the pattern and prevalence of different STIs
      out of total STI clinic attendees, to identify any change in the trend of STIs,
      various epidemiological factors, and behavior of individual diseases. MATERIALS
      AND METHODS: Case records of the patients, attending the STI clinic (Suraksha
      Clinic) attached with Department of Dermatology, Venereology, and Leprosy of a
      tertiary care medical college and hospital of North India from April 2007 to
      March 2014, were analyzed. All the patients were thoroughly examined and
      investigated. RESULTS: This study included a total of 5468 STI clinic attendees
      out of which 3908 were diagnosed to have STIs. Most of the patients were male,
      married, and in the third decade of their lives. In our study, the highest number
      of patients had herpes genitalis, i.e., 850 patients (21.75%) followed by 415
      patients (10.61%) having genital warts. Molluscum contagiosum was present in 239
      patients (6.11%), 106 patients (2.71%) had urethral discharge whereas 81 patients
      (2.07%) diagnosed to have syphilis. Viral infections accounted for 38.48% of
      cases. Human immunodeficiency virus (HIV) positivity was seen in 414 patients
      (10.59%) of total STI cases. CONCLUSION: The trend of STIs is changing from
      bacterial to viral diseases. This is because of the widespread use of
      antibacterial, self-medication, and treatment through national program. STIs
      enhance the susceptibility of an individual to acquire or transmit HIV through
      sexual contact.

PMID- 28442803
TI  - Effects of fitness training on physical fitness parameters and quality of life in
      human immunodeficiency virus-positive Indian females.
AB  - PURPOSE: Highly active antiretroviral therapy has significantly extended survival
      of human immunodeficiency virus (HIV) infected patients. These drugs suppress
      replication of HIV but at the same time, have many physical and mental side
      effects which may affect daily activities of the patients. The present study
      assessed if moderate intensity exercise program helped in enhancing the physical
      fitness and quality of life (QoL) in HIV positive females which may reduce the
      comorbidities associated with the disease and medications. AIM AND OBJECTIVES:
      The aim of this study is to study the effects of moderate intensity physical
      training on physical fitness parameters and QoL in HIV positive females.
      METHODOLOGY: Post IEC approval, a randomized control, single-blinded, parallel
      group trial was conducted on 55 females (20 experimental HIV, 20 control HIV, 15
      control normal) matching the selection criteria. Post informed consent, their
      muscular endurance, flexibility, aerobic capacity, and QoL was assessed. Moderate
      intensity physical exercises were given to experimental HIV and control normal 5
      days/week for 8 weeks and subjects were reassessed for above parameters.
      Intragroup analysis was performed using paired t-test while inter-group was by
      one-way ANOVA with alpha set at <=0.05. RESULTS: Moderate-intensity exercises
      improved muscular endurance (P < 0.05), flexibility (P < 0.05), and aerobic
      capacity (P < 0.05)in experimental HIV and control normal group as compared to
      control HIV group. QoL in experimental HIV showed improvement in all the domains.
      CONCLUSION: Moderate-intensity exercises help improve the physical fitness as
      well as enhance the QoL in HIV positive females.

PMID- 28442805
TI  - Proton pump inhibitors are associated with a reduced likelihood for sexually
      transmitted diseases in women in the emergency department.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) have been shown in cell culture to kill
      Trichomonas vaginalis (TV) at lower half maximal inhibitory concentration values
      than metronidazole (Flagyl), the most common medication used to treat the
      infection. However, there have been no previous clinical investigations to
      determine if PPIs are associated with reduced risk for TV. MATERIALS AND METHODS:
      We examined the records of female patients who received testing in the emergency
      department for TV, Neisseria gonorrhoea (GC), and Chlamydia trachomatis (CT)
      between 2010 and 2014 at two academic medical centers to determine if PPI and
      histamine type 2 receptor antagonist (H2RA) drugs were associated with TV and
      GC/CT infections. RESULTS: We found that H2RAs were associated with an increased
      likelihood for TV (odds ratio [OR]: 2.0, P < 0.0001) and GC and/or CT infections
      (OR: 1.49, P < 0.0001). PPIs were associated with a reduced likelihood for TV
      (OR: 0.75, P < 0.0001) and GC and/or CT infections (OR: 0.57, P < 0.0001). In
      patients infected with GC and/or CT, the likelihood of coinfection with TV was
      reduced in those taking a PPI (OR: 0.64, P = 0.054) and increased in those taking
      an H2RA (OR: 1.62, P = 0.003). CONCLUSIONS: PPIs are associated with a reduced
      risk for TV and GC/CT infection.

PMID- 28442806
TI  - Study of clinical profile of herpes zoster in human immunodeficiency virus
      positive and negative patients at a rural-based tertiary care center, Gujarat.
AB  - BACKGROUND: Herpes zoster usually presents with typically grouped vesicles on
      erythematous base involving single dermatome with self-limiting nature in
      immunocompetent individuals while it may present in extensive form involving
      multiple dermatomes involvement or disseminated form in immunocompromised,
      especially in human immunodeficiency virus (HIV). AIMS AND OBJECTIVES: The aim of
      this study was to study the prevalence of HIV in patients of herpes zoster, to
      compare the clinical presentation of herpes zoster in HIV-infected and
      noninfected patient. MATERIALS AND METHODS: The study was carried out in the
      Department of Dermatology in a Teaching Institute of Gujarat, from June 2008 to
      May 2014 after ethical clearance. The study population included all the patients
      with a clinical diagnosis of herpes zoster. All the patients were investigated
      for HIV infection after written consent. RESULTS: Out of total 688 patients of
      herpes zoster, 35 (5.1%) were HIV-positive, 26 (74.3%) were males and 9 (25.7%)
      were females. Among HIV-positive patients, 29 (82.85%) patients had localized
      dermatomal involvement, 4 (11.42%) patients had multiple dermatomal involvement,
      and only 2 (5.71%) had disseminated zoster while among HIV-negative, 636 (97.40%)
      had localized dermatomal involvement, 14 (2.14%) patients had multiple dermatomal
      involvement, and 3 (0.45%) had disseminated zoster. Cervical dermatome was most
      commonly involved dermatome in patients of HIV. CONCLUSION: Disseminated and
      multiple dermatomal involvement was more commonly involved among HIV-positive
      patients when compared to HIV-negative patients.

PMID- 28442807
TI  - Epidemiology and clinico-investigative study of organisms causing vaginal
      discharge.
AB  - BACKGROUND: Abnormal vaginal discharge is a common clinical problem in
      reproductive age group. It is the second most common problem after abnormal
      uterine bleeding. It is a neglected health problem, most commonly caused due to
      vulvovaginal candidiasis, trichomoniasis, and bacterial vaginosis (BV).
      OBJECTIVES: The present study was conducted to determine the prevalence of common
      organisms causing vaginal discharge and also to know the variety of clinical
      presentation. MATERIALS AND METHODS: A cross-sectional descriptive study was
      conducted in the Skin and STD Outpatient Department of Vinayaka Mission
      Kirupananda Variyar Medical College Hospital, Salem, who presented with abnormal
      vaginal discharge between September 2012 and September 2014. A total of 100 women
      in the reproductive age group who had symptoms of vaginitis were examined. Data
      were coded and analyzed. RESULTS: Out of the 100 patients examined, 77 (77%)
      cases were organism positive. Among the positive cases, BV (27%) was the most
      common microbiological cause of abnormal vaginal discharge, followed by
      trichomoniasis (25%), vaginal candidiasis (22%), combined infection (Candida and
      BV) (3%), and nonspecific cases (23%). CONCLUSION: Out of 100 cases, few cases
      showed discordance between clinical and laboratory diagnosis. This discordance
      can be due to pitfalls in identifying the causative agent clinically or obscuring
      of the findings due to improper treatment received for other ailments. Thus,
      clinico-investigative correlation is more important than other clinical findings
      alone.

PMID- 28442808
TI  - Extramammary Paget's disease of vulva: A rare entity.
AB  - Extramammary Paget's disease is a rare cutaneous, intraepithelial adenocarcinoma
      involving primarily the epidermis but occasionally extending into the underlying
      dermis. The condition typically presents as a red, velvety, pruritic skin rash of
      the vulva region which closely mimics a multitude of other, more common
      conditions. As a result, vulvar Paget's disease is frequently misdiagnosed,
      leading to an often lengthy lag time (an average of about 2-3 years) between the
      onset of symptoms and diagnosis.

PMID- 28442809
TI  - Co-infection of syphilis and hepatitis B with carcinoma penis in a human
      immunodeficiency virus male.
AB  - Human immunodeficiency virus (HIV) infections have a high probability of co
      infections with Syphilis and hepatitis B virus since they share the common routes
      of transmission. We report a 41-year-old HIV male (on antiretroviral therapy for
      the past 6 years) admitted for a complaint of penile ulcer for 2 months. Serology
      for syphilis and hepatitis B were positive. Skin biopsy of the penile ulcer
      confirmed squamous cell carcinoma. Henceforth, the patient was referred to
      oncology department for further management. We present this rare combination of
      syphilis and hepatitis B with carcinoma penis in an HIV patient.

PMID- 28442810
TI  - Fiessinger-Leroy's disease: A rare case report.
AB  - Fiessinger-Leroy's disease (Reiter's disease) is rare and not commonly reported
      in India. This paper reports a case of a 35-year-old male with Fiessinger-Leroy's
      disease, occurring after balanitis. The patient presented with symmetrical
      polyarthritis, pruritic scaly plaques, keratoderma blenorrhagicum, and hematuria
      with histopathology of skin suggestive of Fiessinger-Leroy's disease. The case is
      presented with a view to document the occurrence of the same in India.

PMID- 28442811
TI  - Vulvo-vaginal ano-gingival syndrome: Another variant of mucosal lichen planus.
AB  - Vulvo-vagino-gingival syndrome was described as a distinctive pattern of erosive
      plurimucosal lichen planus (LP), and it is a clinical triad of vulval, vaginal,
      and gingival LP. It can lead to sequelae such as vaginal and urethral stenosis
      which can have severe implications on the quality of life. We report a case of a
      40-year-old female who developed urethral, vaginal, as well as anal stenosis as a
      result of long-term exclusive mucosal LP involving vulvo-vaginal and anal mucosa
      along with oral LP without any other cutaneous involvement. This case is being
      reported because of the rare association of anal LP with vulvo-vagino-gingival
      syndrome and its gross similarity to lichen sclerosus.

PMID- 28442812
TI  - Ramsay Hunt syndrome in a patient with human immunodeficiency virus infection.
AB  - Ramsay Hunt syndrome (RHS) is a rare, severe complication of varicella-zoster
      virus reactivation in the geniculate ganglion, characterized by hearing loss,
      pain, and vesicles in the ear or mouth along with ipsilateral facial palsy.
      Although it is rare, it is more commonly found with immunodeficiency conditions.
      We report a case of a 35-year-old human immunodeficiency virus positive male,
      having CD4+ count of 336/MUl, who presented with RHS and had vertigo, painful
      vesicular eruptions on the right ear and unilateral sensorineural hearing loss.
      He was treated immediately with valacyclovir and prednisolone, and the complete
      recovery was achieved at 6 months after the onset.

PMID- 28442813
TI  - Acral pebbles: A novel manifestation of partially treated syphilis.
AB  - Atypical manifestations in syphilis are known and pose a diagnostic dilemma.
      Early suspicion, timely investigations, diagnosis, and treatment, is the key to
      successful management. We report a patient of secondary syphilis, who presented
      as genital ulcer and small pebbles like eruptions on the palmar aspect of his
      fingers.

PMID- 28442814
TI  - Syphilis incognito: Resurgence of the covert devil - keeping the eyes open.

PMID- 28442815
TI  - Solitary plaque in the perianal region.

PMID- 28442816
TI  - Secondary syphilis: An unusual presentation.

PMID- 28442817
TI  - Exploring the scope of enhanced gonococcal antimicrobial surveillance programme.

PMID- 28442818
TI  - Seroprevalence of transfusion-transmissible infections among replacement and
      voluntary blood donors in a tertiary care hospital.

PMID- 28442819
TI  - An approach to venerophobia in males.
AB  - Venerophobia is a lesser recognized entity in clinical practice though the
      prevalence is on the rise. Our observations of current trends in the Sexually
      Transmitted Diseases (STI) clinic indicate that venerophobia is not an uncommon
      presentation among youngsters following an isolated or multiple episodes of
      sexual contact. This has a major bearing on the mental as well as sexual health.
      So far, there is no published data available in literature on the prevalence and
      extent of the problem. In this paper, we have made an attempt to cover the
      various modes of presentation, laboratory investigations and have outlined an
      approach towards the management of venerophobia in males.

PMID- 28442820
TI  - I Have Never Liked the Term "Compliance".

PMID- 28442821
TI  - Patients With Diabetes and Chronic Liver Disease Are at Increased Risk for
      Overall Mortality: A Population Study From the United States.
AB  - IN BRIEF Chronic liver disease (CLD) and type 2 diabetes have both been linked to
      increased morbidity and mortality. In this study, the impact of CLD and diabetes
      on all-cause mortality was quantified at the population level using U.S.
      population data. Both type 2 diabetes and CLD were found to be independently
      associated with increased mortality (age-adjusted hazard ratio [aHR] 1.98 and
      1.37 for diabetes and CLD, respectively), and having both diabetes and CLD
      substantially increased the risk of mortality (aHR 2.41).

PMID- 28442822
TI  - Effects of Implementing International Association of Diabetes and Pregnancy Study
      Groups Gestational Diabetes Screening on Pregnancy Outcomes at a Small Community
      Teaching Hospital.
AB  - IN BRIEF Traditional methods of screening for and diagnosing gestational diabetes
      mellitus (GDM) have been challenged, leading to the development of new screening
      guidelines by the International Association of Diabetes and Pregnancy Study
      Groups (IADPSG). This study is a retrospective comparison of pregnancy outcomes
      based on the Carpenter and Coustan (CC) and IADPSG screening guidelines. It
      demonstrates that adoption of IADPSG guidelines increased the rate of GDM
      diagnosis and resulted in more women with diet-controlled GDM. However, a
      decrease in adverse pregnancy outcomes was not noted. Interestingly, women
      diagnosed by IADPSG criteria who had diet-controlled GDM had less maternal weight
      gain than those screened with the CC criteria who did not have GDM but did have
      an elevated 1-hour oral glucose tolerance test result.

PMID- 28442823
TI  - Insulin Degludec 200 Units/mL Is Associated With Lower Injection Frequency and
      Improved Patient-Reported Outcomes Compared With Insulin Glargine 100 Units/mL in
      Patients With Type 2 Diabetes Requiring High-Dose Insulin.
AB  - IN BRIEF Many patients with type 2 diabetes require high basal insulin doses,
      necessitating multiple injections, increasing patient burden, and resulting in
      reduced treatment adherence. This randomized, controlled, crossover trial
      compared the efficacy, safety, and patient-reported outcomes for a concentrated
      formulation of insulin degludec (200 units/mL) to those of insulin glargine in
      patients requiring high doses of basal insulin. By offering equivalent glycemic
      control while reducing the rate of confirmed hypoglycemia and the number of
      injections required for administration, insulin degludec 200 units/mL may be
      preferred by patients with type 2 diabetes who require high basal insulin doses.

PMID- 28442824
TI  - Lessons in Care: Insights Into Recent Changes in the American Diabetes
      Association's Clinical Practice Recommendations.

PMID- 28442826
TI  - Call for Submissions: New Clinical Diabetes Department Focuses on Quality
      Improvement and Practice Transformation Initiatives.
AB  - EDITOR'S NOTE: Quality Improvement Success Stories, a new Clinical Diabetes
      department developed in collaboration with the American College of Physicians,
      Inc., and the National Diabetes Education Program, will feature articles and a
      searchable online collection of information about quality improvement and
      practice transformation initiatives in the area of diabetes care. This article
      provides the rationale and article submission process for this new offering.

PMID- 28442825
TI  - Exploring Approaches to Facilitate Diabetes Therapy Intensification in Primary
      Care.

PMID- 28442827
TI  - Five Simple Steps to Optimize Bolus Insulin Therapy in Type 2 Diabetes.

PMID- 28442828
TI  - A Case of Disseminated Sepsis Caused by an Unusual Microorganism in a Patient
      With Diabetes.

PMID- 28442829
TI  - Warts of the Fingertips in a Pediatric Patient With Type 1 Diabetes.

PMID- 28442830
TI  - Information from the American Diabetes Association for people with diabetes: GOOD
      TO KNOW.

PMID- 28442831
TI  - Surgeon's-Virtues and Commandments: a Lesson Learnt from a Human Cell: Cell Is a
      Single True and Full Component of a Human Body, a Friend to Guide Him Truly with
      His Functions.

PMID- 28442832
TI  - Risk Factors for Conversion and Morbidity During Initial Experience in
      Laparoscopic Proctectomies: a Retrospective Study.
AB  - The aim of this study was to determine the predictable factors for conversion
      during laparoscopic proctectomies, and for postoperative morbidity, in order to
      assist in defining the best candidates of patients for initial experience in
      laparoscopic proctectomies for rectal adenocarcinoma. A retrospective analysis of
      consecutive patients who underwent laparoscopic rectal resection for rectal
      adenocarcinoma operated by a single surgeon, between 2005 and 2012, were
      performed. Predictive factors for conversion and for postoperative morbidity were
      analyzed using univariate and multivariate analysis. Sixty-nine patients were
      included. There were 35 (50.7 %) men with a median age of 53 years. Forty-seven
      patients had tumors located below 8 cm from the anal verge, and sphincter
      preserving surgery was performed in 52 (75.4 %) patients. Thirty-four patients
      were operated in the early period (before 2009). Conversion rate was 17.4 %. In
      multivariate analysis, the independent predictive factors for conversion were
      time period (before 2009) (p = 0.007, Exp. 19.9; CI (95 %) 2.2-177.4) and tumors
      located 8 cm above the anal verge (p = 0.028, Exp. 5.23, CI (95 %) 1.2-22.8).
      Twenty-two patients (31.9 %) had a complicated postoperative course. Only male
      gender was associated with postoperative complications (p = 0.01, CI (95 %) 1.3
      11.8). Our study showed that conversion rate is influenced by surgeon's
      experience, and height of the tumor and that male gender is a predisposing factor
      for a higher morbidity rate. These results suggest that women with low rectal
      tumors requiring colo-anal anastomosis or abdomino-perineal resection would be
      the best candidates for early surgeons' experience in laparoscopic proctectomies
      for rectal adenocarcinoma.

PMID- 28442833
TI  - A Randomised Prospective Study to Evaluate Preperitoneal Mesh Repair Versus Onlay
      Mesh Repair and Laparoscopic IPOM in Incisional Hernia Surgery.
AB  - Incisional hernia remains a very common postoperative complication. These are
      encountered with an incidence of up to 20 % following laparotomy. These hernias
      enlarge over time, making the repair difficult, and serious complications like
      bowel obstruction, strangulation and enterocutaneous fistula can occur. Hence,
      elective repair is indicated to avoid these complications. Implantation of a
      prosthetic mesh is nowadays considered as the standard treatment due to low
      hernia recurrence. The most common mesh repair techniques used are the onlay
      repair, sublay repair and laparoscopic intraperitoneal onlay mesh (IPOM).
      However, it is still not clear which technique among the three is superior. A
      study consisting of 30 patients who underwent incisional hernia repair by onlay,
      laparoscopic and preperitoneal mesh repair with abdominoplasty was conducted in
      the Coimbatore Medical College and Hospital. Of the three groups, the
      preperitoneal repair with abdominoplasty was found to have better patient
      compliance and satisfaction with regard to occurrence of complications and
      appearance of the abdominal wall without laxity in a single sitting.

PMID- 28442834
TI  - Parathyroidectomy Decreases Insulin Resistance Index in Patients with Primary
      Hyperparathyroidism.
AB  - Primary hyperparathyroidism (PHPT) has been considered a cause of insulin
      resistance (IR) and impaired glucose metabolism. However, there are conflicting
      results related with the recovery of insulin resistance in patients with PHPT
      following curative parathyroidectomy. Our aim is to evaluate the effects of
      curative parathyroidectomy on IR in patients with PHPT. This is a prospective
      interventional study. Twenty-one consecutive patients with symptomatic PHPT were
      included into the study. All patients underwent parathyroidectomy. Fasting serum
      glucose, calcium, phosphorous, parathormone, plasma insulin, and vitamin D levels
      were measured both at baseline and 2 months after parathyroidectomy. Insulin
      resistance was calculated by homeostasis of model assessment-insulin resistance
      (HOMA-IR). Two months after curative parathyroidectomy, serum levels of calcium
      (p = 0.001), PTH (p < 0.001), insulin (p = 0.003), and HOMA-IR (p = 0.003)
      decreased, while phosphorous levels increased (p = 0.001). During this period, no
      changes were observed at vitamin D and glucose levels. We concluded that curative
      parathyroidectomy decreases HOMA-IR index in patients with PHPT. Studies with
      larger population and longer follow-up period are required to confirm our
      results.

PMID- 28442835
TI  - How much Reliable Is Alvarado Scoring System in Reducing Negative Appendectomy?
AB  - There is still an ongoing debate, especially regarding early diagnosis of acute
      appendicitis. Early surgery leads to inadequate evaluation of acute abdominal
      pain and negative appendectomy, whereas delayed surgery leads to appendicitis
      perforation complications. The diagnosis of this condition is considerably
      difficult, especially due to subtle early symptoms and clinical condition. The
      aim of the present study was to identify whether the Alvarado scoring system
      could reduce the incidence of negative appendectomy in patients who will undergo
      surgery for acute appendicitis. Patients who underwent surgery with acute
      appendicitis prediagnosis were retrospectively classified as negative
      appendectomies (group A) and positive appendectomies (group B) according to
      histological diagnosis. All groups were evaluated for age, gender, Alvarado
      scores, and parameters. Two hundred eighty-one patients were included in the
      study. Group A contained 71 (25.3 %) patients, and group B contained 210 (74.7 %)
      patients. There was a significant difference in WBC, left shift, rebound, and
      change of pain localization between the groups (p = 0.002, p < 0.001, p < 0.001,
      and p = 0.023, respectively). Alvarado scores were significantly different
      between the groups (p < 0.001). In logistic model examination, the major factor
      was the Alvarado score (7 or above) and the minor factor was spreading pain. The
      Alvarado scoring system can be used to reduce negative appendectomy in patients
      who will undergo surgery with acute appendicitis.

PMID- 28442836
TI  - Single-Port Laparoscopic Liver Resection: Largest Turkish Experience.
AB  - Single-port laparoscopic surgery has the advantage of a hidden scar and reduced
      abdominal wall trauma. Although single-port laparoscopic surgery is widely
      performed for other organs, its application is very limited for liver resection.
      Here, we report our experience with nine patients who underwent single-port
      laparoscopic liver resection. Nine patients underwent single-port laparoscopic
      liver resection for the indications of hydatid cyst, hepatocellular carcinoma,
      and colorectal cancer liver metastasis. Nine patients were successfully treated
      with single-port laparoscopic surgery. The operative time was between 60 and 240
      min. The only operative complication was bleeding up to 650 mL in a patient with
      cirrhosis. No postoperative complications occurred. All patients were discharged
      earlier than usual. Single-port laparoscopic liver surgery is a challenging
      surgery. Surgeon with the experience of laparoscopic liver surgery should perform
      the single-port laparoscopic liver surgery. It is technically feasible with a
      good outcome in well-selected patients. Initial cases must be benign lesions to
      avoid jeopardizing oncological safety.

PMID- 28442837
TI  - Emergent Laparoscopic Colectomy Is an Effective Alternative to Open Resection for
      Benign and Malignant Diseases: a Meta-Analysis.
AB  - The aim of this study is to compare the perioperative outcomes between
      laparoscopic and open resections performed for colonic emergencies. A systematic
      search of the literature identified previously published comparative studies
      regarding emergent laparoscopic colectomy (ELC) and emergent open colectomy
      (EOC). Meta-analysis was performed utilizing a pooled odds ratio (OR) for
      dichotomous variables and a weighted mean difference (WMD) for continuous
      variables with 95 % confidence intervals (CIs). Eleven studies involving 752
      patients were identified. Although operation time was noted to be significantly
      shorter for EOC, patients post-ELC had significantly lower overall morbidity (OR
      0.44; 95 % CI 0.30, 0.66; P < 0.0001). Meanwhile, recovery time for post-ELC
      patients was significantly shorter, as was the length of hospital stay (WMD -2.78
      days; 95 % CI -3.17, -2.38; P < 0.00001), the time to regular dietary habits (WMD
      -1.32 days; 95 % CI -2.51, -0.13; P = 0.03), and the time to recover bowel
      movement (WMD -0.55 days; 95 % CI -0.89, -0.22; P = 0.001). Reoperation rate and
      mortality were found to be comparable between ELC and EOC. The R0 resection rate
      and the number of lymph nodes harvested were also comparable between ELC and EOC
      for malignant diseases. Whether for benign or malignant disease, ELC is a safe
      and feasible procedure for colonic emergencies compared with EOC, despite being
      relatively time-consuming.

PMID- 28442838
TI  - Wound Outcome Following Primary and Delayed Primary Skin Closure Techniques After
      Laparotomy for Non-Traumatic Ileal Perforation: a Randomized Clinical Trial.
AB  - To study the effect of primary and delayed primary closure of skin incision on
      wound outcome in patients with non-traumatic ileal perforation, 68 patients of
      ileal perforation were studied in a prospective randomized clinical trial.
      Patients fulfilling inclusion criteria were divided into ileostomy and non
      ileostomy groups, both of which were then randomized into two subgroups each
      depending on whether skin was closed primarily or in a delayed primary manner.
      Wound infection and dehiscence were the main outcome parameters studied. The data
      collected was analyzed using appropriate statistical tools taking significant p
      value at 5 %. Most patients were 21-30 years of age. Male:female ratio was 3.2:1.
      The overall incidence of wound infection was 63 %. Wound infection was strongly
      associated with the incidence of superficial wound dehiscence and total wound
      dehiscence that were 11.76 and 47 %, respectively. Mortality was 10.3 %.
      Methodology of wound closure has no significant impact on incidence of wound
      infection, wound dehiscence, and mortality, although the onset of wound
      complications is significantly delayed with delayed primary closure of the skin.

PMID- 28442839
TI  - The Place of Calprotectin, Lactoferrin, and High-Mobility Group Box 1 Protein on
      Diagnosis of Acute Appendicitis with Children.
AB  - The purpose of this study is to investigate the role of serum calprotectin (CP),
      lactoferrin (LF), and high-mobility group protein B1 (HMGB-1) levels and fecal CP
      and LF levels in differential diagnosis of acute uncomplicated appendicitis from
      other causes of abdominal pain and further from complicated appendicitis.
      Totally, 120 children were included grouped into 4 as: healthy controls, patients
      with right lower quadrant pain with other than surgical causes, patients with
      uncomplicated appendicitis, and patients with complicated appendicitis. Serum CP,
      LF, HMGB-1, C-reactive protein (CRP) levels, and white blood cell (WBC) count
      were studied as well as the fecal CP and LF levels. There was a statistically
      significant difference between control group and both uncomplicated and
      complicated acute appendicitis groups, regarding all parameters. In diagnosis of
      complicated acute appendicitis, area under curve (AUC) for fecal LF, serum CP,
      and serum HMGB-1 were determined as 1.00 and the cutoff level was determined as
      25 MUg/g feces, 670 ng/mL, and 30 ng/mL, respectively. In differential diagnosis
      of uncomplicated and complicated AA, the most accurate parameter was fecal LF
      with an AUC of 0.977. At a 60 MUg/g cutoff value for this variable, sensitivity,
      specificity, and accuracy were 96.7, 93.3, and 95.0 %, respectively. In
      conclusion, HMGB-1, calprotectin, and lactoferrin constitute novel markers in
      diagnosis of AA. Moreover, their levels may be helpful for the clinicians to
      judge about the severity of the condition. Larger studies are warranted to
      determine the diagnostic potential of HMGB-1, LF, and CP in AA diagnosis.

PMID- 28442840
TI  - Assessment of Intracorporeal Suturing in Single-Port Surgery Using an
      Experimental Suturing Model.
AB  - The aim of this study is to assess the difficulty of intracorporeal suturing in
      single-port surgery, using experimental suturing model in dry box. Subjects were
      divided for three groups: seven experienced laparoscopic surgeons, seven surgical
      residents, and seven interns. An experimental suturing model is developed, and
      working angle was set from 0 degrees  to 90 degrees . The completion rate in 0
      degrees  was significantly lower than that in the other angles. Completion rate
      of group A was higher than that of the other groups. Precision of task in group A
      was significantly higher than that of group B and group C in 0 degrees  and 60
      degrees . Stress score in 0 degrees  were significantly higher than that in the
      other angles. Our study demonstrated that intracorporeal suturing in single-port
      surgery seems to be more difficult than conventional laparoscopic surgery. Our
      data should be taken the institution under consideration for introduction of
      single-port surgery.

PMID- 28442841
TI  - Physics for Surgeons Part 3: Why Cyst Is Spherical in Shape?
AB  - Physical examination of any swelling is the first step in making a diagnosis.
      Many a times we see a patient with a spherical swelling, which is usually a cyst.
      The interpretation of physical signs should be based on sound principles of
      physics. In the present paper, we explain physical characteristics of a swelling
      (cyst) using principles of fluid mechanics.

PMID- 28442842
TI  - Aberrant Intrathyroid Tissue: a Report of Intrathyroid Lymph Node Metastasis and
      a Review of Literature.
AB  - Aberrant histological elements have been infrequently reported to exist within
      the intact thyroid gland. In addition to distant metastases to the thyroid, a
      number of ectopic tissue rests and unusual cysts have been described within the
      thyroid gland. In this article, we report the presence of a true intrathyroid
      lymph node and describe the first reported case of intrathyroid lymph node
      metastasis of papillary thyroid cancer. Other reported aberrant intrathyroid
      tissues, possible pathophysiology, diagnostic features and surgical implications
      are also discussed.

PMID- 28442843
TI  - Cognitive and Technical Skill Assessment in Surgical Education: a Changing
      Horizon.
AB  - Assessment is an integral component of training and credentialing surgeons for
      practice. Traditional methods of cognitive and technical appraisal are well
      established but have clear shortcomings. This review outlines the components of
      the surgical care assessment model, identifies the deficits of current evaluation
      techniques, and discusses novel and emerging technologies that attempt to
      ameliorate this educational void.

PMID- 28442844
TI  - A Rare Case of Bilateral Morgagni's Hernia with Intestinal Obstruction and
      Malrotation of the Gut in an Adult Patient with Severe Osteogenesis Imperfecta
      Presenting as Severe Respiratory Distress.
AB  - Osteogenesis imperfecta (OI) is associated with congenital inguinal hernia that
      can occur due to genetic mutation. Morgagni's hernia is a rare congenital
      diaphragmatic herniation and is usually diagnosed in childhood. We present a case
      of an 18-year-old male presenting with bilateral Morgagni's hernia with
      intestinal obstruction with osteogenesis imperfecta with malrotation of the gut.

PMID- 28442845
TI  - Perforative Peritonitis-Gastrointestinal Tract May Not Always Be the Source.
AB  - Perforative peritonitis is the most common surgical emergency in general surgical
      practice. Gastrointestinal perforation is the etiology in the vast majority of
      the patients. However, occasionally, other rare causes may be encountered. One
      such cause of peritonitis is spontaneous perforation of non-gravid uterus.
      Uterine perforation is a potential complication of any intrauterine procedure and
      may be associated with injury to surrounding blood vessels or viscera such as the
      urinary bladder or intestine. Spontaneous uterine perforation is rare and less
      than 50 cases have been reported in the English literature. We are presenting two
      such cases of spontaneous perforation of the uterus in elderly postmenopausal
      women which presented with generalized peritonitis and were clinically
      indistinguishable from gastrointestinal perforation.

PMID- 28442846
TI  - Gunshot Pellet Migration to the Right Ventricle: a Case Report and Literature
      Review.
AB  - The diagnosis and management of injuries of the heart or the great vessels
      continues to be a major surgical challenge in the past and now. This case study
      introduces the conservative management of a patient who developed a venous bullet
      embolus after being shot in the lower extremities. In this case report, we aim to
      review some of the literature on bullet emboli and to raise awareness of its
      existence. It was concluded that for bullets left in the limbs, bullet position
      in relation with peripheral vessels should be evaluated carefully to treat and
      avoid the bullets moving along with the bloodstream.

PMID- 28442847
TI  - Gastrointestinal Neuroectodermal Tumor: a Diagnostic Dilemma.
AB  - Malignant gastrointestinal neuroectodermal tumor (GNET), a rare soft tissue
      sarcoma, is a recently described distinct clinicopathological entity. With only a
      few cases reported in literature till date, there is limited knowledge about the
      behavior as well as diagnosis of this tumor. GNET mimics several other tumors and
      hence presents as a diagnostic challenge to clinicians and pathologists alike. We
      report a case of gastrointestinal neuroectodermal tumors with liver metastasis.

PMID- 28442848
TI  - Dermatofibrosarcoma Protuberance of the Breast: a Diagnostic Challenge.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an uncommon slow growing neoplasm of
      the dermis with tendency to invade the subcutaneous tissues. It presents during
      the third to fourth decade of life and is commonly seen over the trunk,
      extremities and head and neck. DFSP presenting as a breast lump is rare but few
      cases have been reported in the literature. Pre-operative diagnosis with
      mammography, ultrasonography and FNAC is challenging. We report a case of a DFSP
      of the right breast in a middle aged lady with history of recurrent breast lumps
      excised and diagnosed in the past as benign. She presented with progressively
      increasing right breast lump of 2 months duration. She underwent wide local
      excision and histology revealed dermatofibrosarcoma protuberans. In view of its
      local aggressiveness with incomplete surgical margin, mastectomy was performed.

PMID- 28442849
TI  - Operative Management of Enteroatmospheric Fistula in Bjorck 4 Open Abdomen
      Patients by the Help of Laparoscopic Lateral Approach.
AB  - As the open abdomen (OA) management increases, the number of fistula formation
      has also been increasing during the last two decades. These fistulas in OA have
      been defined as enteroatmospheric fistula (EAF). EAF occurring in a frozen OA is
      classified as Bjorck 4 OA. Management of Bjorck 4 OA patient is not easy and
      mortality of these patients is very high in spite of the presence of modern
      treatment modalities. There are a few surgical approaches for treatment of Bjorck
      4 OA patients. One of them is excising the hostile segment by lateral abdominal
      approach from the healthy side or entering from lateral border of OA wound after
      enough time intervals for subsiding of the edematous intestine in acute
      inflammatory reaction in the hostile environment. In this case, we present a
      newly developed surgical technique, called laparoscopic lateral approach which
      was applied to Bjorck 4 OA patient for excising hostile intestinal segment and
      management of the abdominal wall defect.

PMID- 28442850
TI  - The Misconceptions About Surgeons.

PMID- 28442851
TI  - Acceptance of Fibrin Glue Fixation in Lichtenstein Hernia Repair: a Faraway
      Dream.

PMID- 28442852
TI  - Perioperative systemic glucocorticoids in total hip and knee arthroplasty: A
      systematic review of outcomes.
AB  - BACKGROUND: Perioperative systemic glucocorticoids are frequently included in
      multimodal analgesia and antiemetic regimens administered to patients undergoing
      total hip arthroplasty (THA) and total knee arthroplasty (TKA). The objective of
      this systematic review was to evaluate the available randomized controlled trials
      (RCTs) to determine the effect of perioperative systemic glucocorticoids on
      postoperative nausea and vomiting (PONV), pain, narcotic consumption, antiemetic
      consumption, length of stay in hospital, and major complications in patients
      undergoing elective THA or TKA. METHODS: A predefined protocol of eligibility and
      methodology was used for conduct of systematic reviews. Two reviewers screened
      citations for inclusion, assessed methodological quality, and verified the
      extracted data. RESULTS: Six RCTs were included for analysis. Across all outcomes
      analyzed, patients who received glucocorticoids experienced either a benefit or
      no difference compared to those patients who did not receive glucocorticoids.
      There were no instances in which perioperative glucocorticoids had a negative
      impact on any of the outcomes that were analyzed. Furthermore, perioperative
      glucocorticoids had no effect on the rates of superficial infection, deep
      infection, wound complications or deep vein thrombosis (DVT). CONCLUSION: The
      results of this systematic review support the use of perioperative systemic
      glucocorticoids in patients undergoing elective total hip and knee arthroplasty.
      Perioperative glucocorticoids have overall positive outcomes with the benefits
      being more robust in those patients undergoing TKA compared to THA.
      Glucocorticoids did not increase the occurrence of major complications. There is
      limited data to support the conclusion that they can reduce length of stay in
      hospital.

PMID- 28442853
TI  - Removal of a well fixed cemented acetabular component using biomechanical
      principles.
AB  - BACKGROUND: Removal of well fixed components can be a complex problem facing an
      orthopaedic surgeon during revision hip arthroplasty. As the burden of revision
      hip surgery increases, techniques have been described to enable safe and reliable
      removal of well fixed components. Removal of well fixed cemented components
      requires different considerations to the removal of cemented components.
      Polymethylmethacrylate bone cement and polyethylene have unique biomechanical
      properties. METHOD: We present a step-by-step technique to reliably and safely
      remove a well fixed cemented acetabular component and underlying cement during
      revision hip arthroplasty. RESULTS: This reproducible technique is presented with
      intra-operative photography and a detailed description of the necessary steps to
      remove a well fixed cemented acetabular component. CONCLUSION: Consideration of
      important underlying biomechanical principles of polymethylmethacrylate bone
      cement and polyethylene can aid the safe removal of a well fixed cemented
      acetabular component in revision hip surgery, reducing risk to underlying bone.

PMID- 28442854
TI  - Biceps Rerouting after Forearm Osteotomy: An Effective Treatment Strategy for
      Severe Supination Deformity in Obstetric Plexus Palsy.
AB  - Study Design Retrospective cohort study. Objective Supination deformity in
      obstetric brachial plexus injury can have debilitating consequences for the
      functionality of the hand. Surgical treatment by a forearm osteotomy has a
      recurrence rate of 20 to 42%. As a complement to forearm osteotomy, a biceps
      rerouting may improve outcome. Methods Children with residual brachial plexus
      injury, who had a forearm osteotomy for a supination contracture and had a
      postoperative decrease of pronation to 50 degrees or less, were indicated for a
      biceps rerouting. Shoulder, elbow and hand function, biceps strength, Mallet
      score, and Raimondi score were assessed with a minimum follow-up of 2 years.
      Results Five patients (median age: 8 years; range: 4-10) underwent biceps
      rerouting between 2008 and 2012. Median follow-up time was 6.8 years (range: 3.2
      7.0 years). Passive pronation increased in all cases (median 0 degree at baseline
      to 80 degrees at final follow-up). Active pronation also increased. Active median
      wrist extension was -30 degrees at baseline and 45 degrees at follow-up. Biceps
      strength and grip strength improved in two cases. No recurrences were present.
      Conclusion The sequentially planned surgical treatment of forearm osteotomy and
      biceps rerouting should be considered in the treatment of severe supination
      deformity, as it is effective in improving pronation of the forearm and hand
      function, without recurrence at follow-up. Level of Evidence/Type of Study Level
      III, case series, therapeutic study.

PMID- 28442855
TI  - The Functional Outcome of Mini Carpal Tunnel Release.
AB  - Introduction Carpal tunnel syndrome (CTS) is one of the most common compression
      neuropathies in the upper limbs and requires surgery if conservative treatment
      fails. This study assessed the functional outcome of vertical mini carpal tunnel
      release (CTR) at distal wrist crease. Objective To evaluate prospectively the
      safety, effectiveness, and reproducibility of vertical mini-open blind technique
      for CTR. Methods In total, 36 patients (40 hands) aged between 22 and 71 years
      with mild to moderate CTS based on nerve conduction studies were selected and
      screened based on inclusion and exclusion criteria. The surgery was done with
      vertical mini-incision CTR at distal wrist crease. The preoperative and
      postoperative clinical outcomes and grip strength were evaluated with Levine-Katz
      questionnaire and JAMAR Hydraulic Hand Dynamometer with 3 months follow-up after
      surgery. Results The mean score for both symptom severity and functional status
      reduced and mean handgrip strength improved 29.5% at 3 months after surgery. All
      the patients were satisfied with the cosmetic outcome of the scar. Three patients
      had scar tenderness. All patients were able to return to work within 4 weeks
      after surgery, except one who developed chronic regional pain syndrome.
      Conclusion The vertical mini-open blind technique has been shown to be safe and
      easily reproducible and has short recovery period. All patients return to good
      functional status 3 months postoperative.

PMID- 28442856
TI  - Functional Outcome of Fixation of Complex Intra-articular Distal Radius Fractures
      with a Variable-Angle Distal Radius Volar Rim Plate.
AB  - Aim To evaluate the outcome of these complex fractures using a volar approach and
      the DePuy Synthes variable-angle 2.4-mm distal radius rim plate. This plate is
      precontoured to the volar rim for placement distal to the watershed line allowing
      purchase of the rim fragment of the lunate facet. Its low profile and smooth
      edges are designed to minimize flexor tendon irritation. Method We report on a
      consecutive series of far distal AO-23B3 and AO-23C3 fractures treated using this
      plate in a tertiary hand center between November 2011 and May 2014. Range of
      motion, grip strength, and complications were assessed at the final clinical
      review. Disabilities of the arm, shoulder, and hand (DASH) and patient evaluation
      measure (PEM) scores were assessed at 12 months after surgery. Results Twenty-six
      patients were included in this review. Six patients were lost to follow-up at 3
      months. This plate was used in isolation in 17 cases, and in combination with a
      dorsal plate, in cases of dorsal instability after volar plating, in 10 patients.
      DASH and PEM scores 1 year after surgery were 17.6 and 27%, respectively. Visual
      analog scores for patient treatment satisfaction and severity of pain showed good
      satisfaction with treatment and mild intermittent pain on activity. Postoperative
      range of motion was variable and grip strength was of 71% of the uninjured
      contralateral side. There were no cases of flexor or extensor tendon rupture.
      Tendon irritation was noted in two patients. Removal of metal was performed in
      four patients. Loss of reduction occurred in one case and neurologic
      complications in two cases. Conclusion This implant is specifically designed for
      the management of far distal complex intra-articular fractures of the distal
      radius. Despite the complexity of these fracture patterns and the challenge they
      pose to accurate reduction and stable fixation, outcomes were satisfactory in
      this small series. There were no cases of tendon rupture. Removal of metal is not
      necessary in all cases, but prompt removal should be performed in cases of tendon
      irritation in view of the risk of tendon rupture.

PMID- 28442857
TI  - Influence of Blood Flow on the Neuroma Formation after Transposition of the Nerve
      Stump into Vein: Experimental and Clinical Study.
AB  - We study the influence of blood flow on the neuroma formation after transposition
      of the nerve stump into a vein. A total of 30 rats were divided into two groups.
      In group (I), a 10-mm segment of the femoral vein was excluded from the blood
      stream. A venotomy was performed in the middle of this segment. The proximal
      nerve stump of femoral nerve was transposed into the lumen of the femoral vein
      via a venotomy and held with an epineural suture through the venous wall. In
      group (II), the same technique was used as in group (I) but without exclusion of
      the vein segment from blood flow. The control side of the femoral nerve was
      transected and then was left in place. All animals were sacrificed after 28
      weeks. Histopathological evaluation was performed postoperatively; serial
      transverse sections were made to find the largest diameter of the neuroma.
      Selected specimens were processed for electron microscopy examination. The
      following parameters were assessed in both the groups: cross-sectional area of
      neuromas; myelinated axons; and neural tissue to connective tissue ratio. In
      group (I), the proximal end of the tibial nerve formed a nonclassic neuroma. In
      group (II), the proximal end of the tibial nerve formed a nonclassic neuroma
      smaller in diameter than group (I). The proximal end of the femoral nerve of the
      control sides in both groups formed a classic neuroma larger in diameter than the
      experimental sides in both the groups. A Kruskal-Wallis H test showed that there
      was a statistically significant difference in myelinated axons between the
      different groups, X2 (3) = 36.19, p < 0.001. The average neural tissue to
      connective tissue ratio in the control group (I) ranged from 39.2 to 85.8%, but
      on the experimental side, it was more or less equalized. The average of a neural
      tissue to connective tissue ratio of the group (II) ranged from 59.1 to 63.9% in
      the treatment sides as compared to 28.6 to 82.4% in the control sides. The
      clinical experience utilizing the same technique in the treatment of 10 patients
      of painful neuromas of the superficial radial nerve and digital nerves were
      presented with encouraging results. The blood flow has a considerable effect on
      neuroma formation. We recommend a further study to know the fine details about
      the exact role of blood as the bloodstream may carry away neurotrophic factors
      that may also be released by the nerve stump itself.

PMID- 28442858
TI  - Observer Variability in Evaluating Pisotriquetral Osteoarthritis using
      Pisotriquetral View.
AB  - A pisotriquetral (semilateral) view of the wrist may improve the assessment of
      pisotriquetral osteoarthritis (OA), but its reliability and reproducibility are
      unclear. The purpose of this cross-sectional observer study was to investigate
      (1) the inter- and intraobserver agreement of evaluating pisotriquetral OA using
      pisotriquetral views with a special focus on sclerosis, joint space width (JSW)
      narrowing and osteophyte formation, and (2) the incidence of these latter
      radiographic features in patients suspected for pisotriquetral OA. Five
      independent observers rated independently at two different occasions 27
      pisotriquetral views from patients treated for ulnar-sided wrist pain suspected
      for pisotriquetral OA requiring a pisiform resection. The agreement was
      calculated using kappa statistic. Agreement between observers ranged from 0.38
      (fair) to 0.56 (moderate). Average intraobserver agreement ranged from 0.43
      (moderate) to 0.52 (moderate). In 36% of the ratings, JSW narrowing was observed,
      followed by osteophyte formation (30%) and sclerosis (28%). Observers found it
      especially difficult to detect JSW narrowing. Despite the availability of a
      pisotriquetral view to enhance visualization of the pisotriquetral joint,
      assessment of the specific features indicating pisotriquetral OA leads to only
      fair-to-moderate agreement. This limits the applicability of a radiographic
      assessment. A rationale for a more reliable radiologic approach in assessing the
      level of pisotriquetral OA is needed, which may require the use of more advanced
      imaging techniques.

PMID- 28442859
TI  - Digital Myopericytoma: A Case Report and Systematic Literature Review.
AB  - A myopericytoma (MP) is an exceedingly rare perivascular tumor of unknown
      etiology. Given their potential for mimicry and malignancy, MP tumors pose a
      unique challenge for surgeons and may be overlooked on differential diagnosis. We
      present a case report of an otherwise healthy 33-year-old right-hand dominant
      male who presented to our outpatient clinic with a 2-month history of painless
      swelling and erythema of the pulp of his left index finger. Subsequent plain film
      X-ray showed near-complete bony destruction of his distal phalanx. Pathological
      evaluation of an incisional biopsy showed a benign variant of MP. The lesion was
      treated by excision with tumor shelling, and there was no evidence of recurrence
      81 days postoperatively. A systematic literature review of the management and
      outcome of all known cases of hand and wrist MP is presented.

PMID- 28442860
TI  - Scedosporium prolificans Septic Arthritis.

PMID- 28442861
TI  - Congenital Familial Clinodactyly of Index Finger with Proximal Delta Phalanges
      and Ulnar Deviation.

PMID- 28442862
TI  - A Great Chronic Expanding Hematoma on the Palm of the Hand.

PMID- 28442863
TI  - Radial Nerve Injury after Venipuncture.

PMID- 28442864
TI  - Multiple Plexiform Neurofibroma of the Hand Misdiagnosed as Ganglion Cyst.

PMID- 28442865
TI  - Microsurgery Training: Does It Improve Surgical Skills?

PMID- 28442866
TI  - Lateral Subluxation of the Fifth Carpometacarpal Joint.

PMID- 28442867
TI  - A Symbol of Resilience: The Prayerful Hands of Mary, Queen and Mother.

PMID- 28442868
TI  - Use of Biobrane Glove Finger Sleeves on Nonintended Burn Wounds of the Hand-A
      Cost-Saving Method.

PMID- 28442869
TI  - Effect of Oil Application, Age, Diet, and Pigmentation on the Tensile Strength
      and Breaking Point of Hair.
AB  - BACKGROUND: Hair strength depends on various factors such as nutrition,
      environmental factors, sunlight, oiling, aging, conditioner, etc. AIM: To compare
      the tensile strength and breaking point of the hair shaft between (1) vegetarian
      and nonvegetarian. (2) Those who regularly apply and those who do not apply oil.
      (3) Pigmented and nonpigmented hair, (4) childhood and elderly. MATERIALS AND
      METHODS: Hair fibers were mounted in tensile strength testing machine Zwick/Roell
      Z010 and gradual force was administered. The elongation of hair fiber in mm and
      the maximum force required to break the hair strand were recorded for each fiber.
      RESULTS: Elasticity of the children's hair was more than the elasticity of adult
      (P = 0.05) although tensile strength in children hair was not statistically
      significant (>0.05). Similarly, the tensile strength was more among those who
      regularly consumed nonvegetarian food but the difference was not statistically
      significant (P > 0.05). There was no statistically significant difference in
      other groups (P > 0.05). CONCLUSION: Elasticity in children hair is statistically
      more than elderly hair although there is no significant change in tensile
      strength.

PMID- 28442870
TI  - Serum Vitamin D3 Levels and Diffuse Hair Fall among the Student Population in
      South India: A Case-Control Study.
AB  - INTRODUCTION AND AIMS: Hair fall is a common problem faced by many younger
      people, which has variety of risk factors. Vitamin D3 has emerged as a molecule
      with key role to play in various disorders. This study was done to assess its
      role in diffuse hair fall among student population. MATERIALS AND METHODS: This
      was a case-control study including young adults presenting with complaints of
      hair fall (>100 a day) as cases, with age-matched healthy controls. Vitamin D3
      levels were measured in all the patients. Data analysis was done using
      Statistical Package for Social Sciences version 11.5 software and significance
      was tested using Chi-square test and binary logistic regression analysis.
      RESULTS: Atotal of 44 participants were enrolled; 22 in each arm. The mean age of
      the study population was 20.89 years (standard deviation: 1.49). The median value
      of Vitamin D was 6.80 (interquartile range - 5.350-16.63) for the study
      population. Overall, 81.8% cases had Vitamin D deficiency compared to 45.5% of
      controls and this difference was statistically significant (P = 0.007).
      Furthermore, females had a statistically significant difference in Vitamin D
      levels between cases and controls. Higher level of full sleeve cloth usage,
      sunscreen lotion application, and lesser sun exposures were seen among cases
      although these differences were not statistically significant. The levels of
      Vitamin D3 were not significantly different among Indians, nonresident Indians,
      and foreigners. None of the cases had normal Vitamin D values whereas 4.5%
      controls fell in the normal category. CONCLUSIONS: Female patients with diffuse
      hair fall were found to have significantly low Vitamin D3 levels among student
      population.

PMID- 28442871
TI  - Epithelioma Adenoides Cysticum: A Report of Two Cases in a Family.
AB  - Epithelioma adenoides cysticum or multiple trichoepitheliomas are rare benign
      hamartomas arising from the hair germ. A 35-year-old female presented with
      multiple skin-colored firm papules and nodules mainly affecting the central face,
      scalp, and external ear canal since the age of 9 years. The lesions gradually
      increased with age. Her 13-year-old son also had similar but smaller lesions on
      the central face. Histopathology was consistent with trichoepithelioma.

PMID- 28442872
TI  - Olmsted Syndrome in a Family.
AB  - Olmsted syndrome (OS) is a rare disorder characterized by the combination of
      periorificial, keratotic plaques, and bilateral palmoplantar keratoderma.
      Synonyms are mutilating palmoplantar keratoderma with periorificial keratotic
      plaques (ORPHA659, MIM #614594 and #300918). A number sign (#) is used with this
      entry because of evidence that mutilating palmoplantar keratoderma with
      periorificial keratotic plaques (OS) is caused by heterozygous mutation in the
      TRPV3 gene on chromosome 17p13.2. We report three cases of OS, two females and
      one male in the same family, who presented with palmoplantar keratoderma, sparse
      scalp hair, cheilitis, and periorificial fissures. We are reporting the cases due
      to the rarity of occurrence and to highlight the trichoscopy findings.

PMID- 28442873
TI  - Anagen Effluvium Following Acute Colchicine Poisoning.
AB  - We present a case of a 17-year-old girl admitted to the Psychiatric Department
      recovering from a suicide attempt with colchicine. One week after poisoning, a
      sudden onset of hair loss was observed. Positive hair pull test and trichoscopy
      demonstrated the presence of anagen hairs with pigmented long roots covered by
      the root sheaths. Colchicine poisoning is an uncommon, but potentially life
      threatening toxicologic emergency. An overdose of colchicine inhibits cell
      division, and thus the most affected organs are those which have a high rate of
      cell turnover. Hair loss resulting from colchicine poisoning presents as anagen
      effluvium, as it occurs with an exposure to toxic chemicals. Pharmacotherapy or
      specific treatment is not usually required, since the follicle resumes its normal
      activity after withdrawal of the antimitotic factors.

PMID- 28442874
TI  - Graham-Little-Piccardi Syndrome: A Lens Through beyond What is Known.
AB  - Graham-Little-Piccardi syndrome (GLPS) is a rare form of follicular lichen planus
      and comprises cicatricial alopecia of the scalp, noncicatricial alopecia of the
      axillae, and/or pubis and spinous follicular papules involving the trunk and
      extremities. We herein report a classic case of GLPS in a 49-year-old female.
      Uniqueness of our case is due to its additional features of frontal fibrosing
      alopecia (FFA). Although overlap between GLPS and FFA has been mentioned in
      literature, such numbers are scanty. Therapeutic response with oral steroid and
      retinoid is also far better in contrast to what is described in the existing
      literature.

PMID- 28442875
TI  - Extreme Phenotype of Epidermal Growth Factor Receptor Inhibitor-induced
      Destructive Folliculitis.
AB  - Due to the increasingly widespread use and side effect profile of epidermal
      growth factor receptor inhibitors (EGFRIs), cutaneous side effects of these drugs
      are frequently encountered. The EGFR is expressed on keratinocytes and
      fibroblasts. Inhibition of EGFR can produce a range of cutaneous adverse effects,
      the most frequent being a characteristic acneiform skin eruption. As the latter
      is associated with good anti-neoplastic responses, the onset of EGFRI-induced
      acneiform skin eruption is typically viewed as a positive sign by patients and
      physicians. It can usually be treated well with standard acne drugs, but in rare
      cases, the skin eruption can be so severe that systemic therapy and/or
      interruption of EGFRI treatment are required. One of the severest forms of EGFRI
      induced skin eruption occurring on the head and neck area resembles folliculitis
      decalvans. Here, we discuss the management of such a case seen in our department.
      In addition, we present an analysis of tumor necrosis factor-alpha, interleukin
      1beta (IL-1beta), and IL-17A expression based on immunohistochemical stains and
      qPCR.

PMID- 28442876
TI  - Idiosyncratic Findings in Trichoscopy of Tinea Capitis: Comma, Zigzag Hairs,
      Corkscrew, and Morse Code-like Hair.
AB  - Dermoscopy is a method of growing significance in the diagnoses of dermatological
      pigmented skin diseases. However, in my case, mycology culture was negative and
      successful treatment was given on the basis of trichoscopy and wood lamp
      examination. I hereby describe a young boy with tinea capitis, multiple "comma
      hairs" and "zigzag hair" and a subtle additional feature "Morse code-like hair"
      when intensification was applied. Dermatoscopic aspects found skin Type 2 in a
      child of as a distinctive dermoscopic finding.

PMID- 28442877
TI  - Aplasia Cutis Congenita: Trichoscopy Findings.
AB  - Aplasia cutis congenita (ACC) is a rare disorder characterized by localized
      absence of skin that most commonly affects the scalp. We present a case of ACC in
      a 45-day-old girl and the dermoscopic findings. Dermoscopy has shown to be an
      easy, fast and useful method for the diagnosis of this condition.

PMID- 28442878
TI  - Loose Anchoring of Anagen Hairs and Pili Torti due to Erlotinib.
AB  - Erlotinib is a selective epidermal growth factor receptor inhibitor utilized in
      the treatment of solid tumors. Cutaneous side effects, including changes in hair
      texture and alopecia, have been described. In this case report, we describe two
      patients with a new finding of loose anagen hairs and pili torti leading to
      nonscarring marginal and diffuse alopecia and discuss potential mechanisms
      underlying erlotinib-induced hair changes.

PMID- 28442879
TI  - Methotrexate in Alopecia Areata: A Report of Three Cases.
AB  - There are few studies about systemic treatment in severe cases of alopecia areata
      (AA), especially in the pediatric population. Although there is more experience
      with systemic corticosteroids, recent reports have suggested methotrexate (MTX)
      as an alternative treatment, with a relatively good outcome. We describe three
      cases of AA in children treated with MTX, two of them with successful results.

PMID- 28442880
TI  - Trichoscopic Patterns in Squamous Cell Carcinoma: : A Case Report.
AB  - Squamous cell carcinoma (SCC) is the second most cutaneous malignancy after basal
      cell carcinoma (BCC) with increasing incidence. In the view its nodular
      manifestation; it can appear similar to nodular BCC, atypical fibroxanthoma,
      sclerosing liposarcoma and desmoplastic melanoma. Prognostic and therapeutic
      implications are different in all these conditions and thus their distinction
      becomes important. Trichoscopy is a simple and non-invasive technique to
      visualize certain morphological features of skin lesions and it improves the
      diagnostic accuracy for melanocytic and nonmelanocytic pigmented lesions. Here, a
      case is reported wherein trichoscopic patterns were useful in the diagnosis of
      SCC on the scalp. To the best of our knowledge, this is the first report on
      trichoscopic patterns in SCC from India.

PMID- 28442881
TI  - Cutaneous Hybrid Tumor Composed of Epidermal Cyst and Cystic Pilomatricoma:
      Unusual Presentation in a Child.
AB  - We report a rare case of cutaneous hybrid tumor composed of epidermal cyst and
      cystic pilomatricoma that presented in an unusual way in a child. A 14-year-old
      teen girl presented with a skin lesion on the inner side of the left arm,
      approximately at the level of the elbow. The lesion was initially observed 5
      months before and was continuously increasing in size during that time resembling
      other benign or malignant cutaneous tumors.

PMID- 28442882
TI  - Comparative Analysis of Immunopathological Features of Lichen Planopilaris and
      Female Patients with Frontal Fibrosing Alopecia.
AB  - BACKGROUND: Frontal fibrosing alopecia (FFA) is a disorder characterized by
      progressive cicatricial alopecia (CA). Its classification as a clinical variant
      of lichen planopilaris (LPP) or as a unique disorder is controversial. The
      presence of Langerhans cells within the bulge area and the sebaceous epithelium
      and the presence of lymphocytic infiltrate in this area in CA have led to a
      series of hypotheses, although limited, about their development. To our
      knowledge, scarce is the literature demonstrating immunoanalytical studies
      comparing both disorders. OBJECTIVE: The authors sought to describe diagnostic
      findings, comorbidities, and immunopathological features of female patients with
      FFA as compared to LPP. MATERIALS AND METHODS: This retrospective single-center
      study included patients given the diagnosis of FFA or LPP. The LPP activity index
      was used to evaluate objective signs and subjective symptoms. Biopsy specimens
      were obtained from active, inflammatory areas of the scalp, and the inflammatory
      infiltrate intensity and quality were compared. Direct immunofluorescence for
      IgA, IgM, and IgG and immunohistochemistry to demonstrate the expression of CD1a,
      CD3, CD4, CD8, CD68, and 2,3-dioxygenase indoleamine were performed. RESULTS:
      Twenty female patients (10 patients with FFA and 10 patients with LPP) were
      included in the study. Histopathological findings evidenced reduced number of
      hair follicles and perifollicular fibrosis in both disorders. Immunofluorescence
      findings resulted positive in 50% of FFA cases and 40% of LPP cases. CONCLUSION:
      Although clinically different, our findings suggest that there are, to date, no
      histological or immunological findings that allow us to accurately separate these
      two forms of scarring alopecia, namely FFA and LPP.

PMID- 28442883
TI  - A Comment on Frontal Fibrosing Alopecia (Axel Munthe's Syndrome).
AB  - Frontal fibrosing alopecia (FFA) represents a peculiar condition with a quasi
      symmetrical, marginal alopecia along the frontal and temporal hairline with
      scarring. Steven Kossard is credited with the original description of the
      condition in 1994. Since its first description, FFA has become increasingly
      common while its etiology has remained obscure. While FFA has been related to
      lichen planopilaris, in fact, the pattern of clinical disease presentation might
      be more specific for the condition than the underlying inflammatory autoimmune
      reaction. It has been speculated as to whether FFA existed before Kossard's
      original report since artistic depictions dating from the 15th to 16th century
      often show a high frontotemporal hairline. Rather, these represent fashionable
      forms of frontal pseudo-alopecia than FFA. Nevertheless, there is compelling
      evidence that FFA existed well before 1994 from the Swedish Physician Axel
      Munthe's (1857-1948) account of the distinctive features of the condition in his
      book of memoirs "The Story of San Michele." Therefore, Axel Munthe is to be
      acknowledged the first description of FFA in 1929.

PMID- 28442884
TI  - Cone dystrophy or macular dystrophy associated with novel autosomal dominant
      GUCA1A mutations.
AB  - PURPOSE: Sixteen different mutations in the guanylate cyclase activator 1A gene
      (GUCA1A), have been previously identified to cause autosomal dominant cone
      dystrophy (adCOD), cone-rod dystrophy (adCORD), macular dystrophy (adMD), and in
      an isolated patient, retinitis pigmentosa (RP). The purpose of this study is to
      report on two novel mutations and the patients' clinical features. METHODS:
      Clinical investigations included visual acuity and visual field testing, fundus
      examination, high-resolution spectral-domain optical coherence tomography (OCT),
      fundus autofluorescence imaging, and full-field and multifocal electroretinogram
      (ERG) recordings. GUCA1A was screened by Sanger sequencing in a cohort of 12
      French families with adCOD, adCORD, and adMD. RESULTS: We found two novel GUCA1A
      mutations-one amino acid deletion, c.302_304delTAG (p.Val101del), and one
      missense mutation, c.444T>A (p.Asp148Glu)-each of which was found in one family.
      The p.Asp148Glu mutation affected one of the Ca2+-binding amino acids of the EF4
      hand, while the p.Val101del mutation resulted in the in-frame deletion of Valine
      101, localized between two Ca2+-binding aspartic acid residues at positions 100
      and 102 of the EF3 hand. Both families complained of visual acuity loss worsening
      with age. However, the p.Asp148Glu mutation was present in one family with adCOD
      involving abnormal cone function and an absence of macular atrophy, whereas
      p.Val101del mutation was encountered in another family with adMD without a
      generalized cone defect. CONCLUSIONS: The two novel mutations described in this
      study are associated with distinct phenotypes, MD for p.Val101del and COD for
      p.Asp148Glu, with no intrafamilial phenotypic heterogeneity.

PMID- 28442885
TI  - Complement C5a receptor knockout has diminished light-induced
      microglia/macrophage retinal migration.
AB  - PURPOSE: The complement system is involved in the pathogenesis of age-related
      macular degeneration (AMD). Because activated microglia are also associated with
      AMD, we studied the relationship between complement anaphylatoxin receptors and
      microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a
      receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced
      migration of microglia/macrophages into the mouse outer retina via
      immunofluorescence and real-time quantitative PCR. RESULTS: We found that the
      mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement
      alternative pathway, Cfb and Cfd, were all upregulated after light exposure.
      Retinal Iba1-positive microglia/macrophages express receptors for C3a and C5a.
      Light damage increased the number of retinal Iba1-positive cells and the mRNA
      levels of Iba1. Compared with the wild-type (WT) mice, these increases were
      attenuated in the C5aR KO mice but not in the C3aR KO mice. CONCLUSIONS: C5aR but
      not C3aR promoted the recruitment of microglia/macrophages. These divergent
      properties of complement anaphylatoxins in the light damage model provide a
      rationale for testing the differential effects of these receptors in additional
      retinal and neurodegeneration models.

PMID- 28442886
TI  - Hydroxychloroquine for treatment of rheumatoid arthritis: multifocal
      electroretinogram and laser flare-cell photometry study.
AB  - PURPOSE: To evaluate early changes in multifocal electroretinogram (mfERG) and
      subclinical aqueous humor flare and cellularity in patients receiving
      hydroxychloroquine (HCQ) as treatment for rheumatoid arthritis. METHODS: Ten
      patients receiving treatment with HCQ and no ophthalmic symptoms were enrolled.
      After complete ocular examination, mfERG and laser flare-cell photometry were
      performed. Patients were also divided into two subgroups with HCQ cumulative dose
      (CD) higher or lower than 500 g. Results obtained were compared with a control
      group of ten healthy subjects and statistical analysis was performed. RESULTS: In
      patients receiving HCQ treatment, mfERG P1-wave in ring 2 showed a significant
      reduction in amplitude and a significant increase in latency compared to healthy
      control subjects, respectively resulting in 1.143 MUV vs 1.316 MUV (P=0.040) and
      38.611 ms vs 36.334 ms (P=0.024). These changes are highly related to CD.
      Furthermore, when using the laser flare-cell photometry, a significant increase
      in aqueous humor flare and cellularity was shown in patients with CD higher than
      500 g, resulting in a mean value of 14.4 ph/ms compared to 8.1 ph/ms in patients
      with CD lower than 500 g (P=0.0029). These reports appear highly related to CD
      (P=0.001). Receiver operating characteristic curve analysis showed mfERG P1-wave
      amplitude in ring 2 as the most sensitive value in detecting early HCQ-related
      retinopathy. CONCLUSION: MfERG was shown to be a very sensitive test in detecting
      early retinal toxicity and should be used for the screening of patients receiving
      HCQ treatment. Although less sensitive, laser flare-cell photometry can provide
      further information to evaluate early toxic retinal cell damage.

PMID- 28442887
TI  - Management of Duane retraction syndrome with prismatic glasses.
AB  - PURPOSE: To report the results of using prismatic glasses for Duane retraction
      syndrome (DRS). METHODS: Data were obtained from the records of patients who were
      evaluated during the year 2000 in the Strabismus Unit of the Beyoglu Eye Training
      and Research Hospital. The average follow-up was 12.2+/-17.7 months. In all
      cases, 2 main variables were evaluated: horizontal deviation in the primary
      position and face turn. Prismatic glasses were provided to patients according to
      the degree of shift in the primary position. RESULTS: The mean age of patients
      was 11.2 years. An analysis was performed on the data collected from 12 cases; 7
      patients were females (58.3%) and 5 were males (41.7%), with 11 (91.7%) cases
      being of type I DRS. All 12 patients had abnormal head posture (face turn) and an
      angle of mean deviation equaling 10 PD (prism dioptri). CONCLUSION: Treatment was
      individualized on a case-by-case basis. Prismatic glasses are useful for
      eliminating abnormal head posture and ocular misalignment in selected cases.

PMID- 28442888
TI  - New developments in the treatment of multiple myeloma - clinical utility of
      daratumumab.
AB  - Multiple myeloma is a clonal disorder of plasma cells that is currently
      considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is
      highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1
      monoclonal antibody that targets CD38, and has antimyeloma effects through
      several mechanisms. Single-agent trials show surprising activity in heavily
      pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is
      added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have
      demonstrated significantly improved progression-free survival with acceptable
      toxicity. In this review, we discuss the mechanism of action, pharmacology and
      pharmacokinetics of daratumumab and review the available clinical data in detail.
      We examine how daratumumab interferes with transfusion testing due to the
      expression of CD38 on the red blood cells, leading to potential difficulties
      releasing blood products. Daratumumab also affects disease assessments in
      multiple myeloma, including serum protein electrophoresis, immunofixation and
      flow cytometry. Strategies to mitigate these effects are discussed. The optimal
      use of daratumumab has yet to be decided, and several trials are ongoing in the
      relapsed and upfront setting. We discuss the potential upfront role of this
      exciting therapy, which has significant potential for increased minimal residual
      disease negativity and improved progression-free survival even in high-risk
      groups.

PMID- 28442889
TI  - CUL4A promotes cell invasion in gastric cancer by activating the NF-kappaB
      signaling pathway.
AB  - Cullin 4A (CUL4A) overexpression has been reported to be involved in the
      carcinogenesis and progression of many malignant tumors. However, the role of
      CUL4A in the progression of gastric cancer (GC) remains unclear. In this study,
      we explored whether and how CUL4A regulates proinflammatory signaling to promote
      GC cell invasion. Our results showed that knockdown of CUL4A inhibited GC cell
      migration and invasion induced by lipopolysaccharide (LPS) stimulation. We also
      found that both CUL4A and nuclear factor-kappa B (NF-kappaB) protein expressions
      were enhanced by LPS stimulation in HGC27 GC cell lines. Furthermore, knockdown
      of CUL4A decreased the protein expression of NF-kappaB and mRNA expression of the
      downstream genes of the NF-kappaB pathway, such as matrix metalloproteinase (MMP)
      2, MMP9, and interleukin-8. Our immunohistochemistry analysis on 50 GC tissue
      samples also revealed that CUL4A positively correlated with NF-kappaB expression.
      Taken together, our findings suggest that CUL4A may promote GC cell invasion by
      regulating the NF-kappaB signaling pathway and could be considered as a potential
      therapeutic target in patients with GC.

PMID- 28442890
TI  - Justification of disintegration testing beyond current FDA criteria using in
      vitro and in silico models.
AB  - Drug product performance testing is an important part of quality-by-design
      approaches, but this process often lacks the underlying mechanistic understanding
      of the complex interactions between the disintegration and dissolution processes
      involved. Whereas a recent draft guideline by the US Food and Drug Administration
      (FDA) has allowed the replacement of dissolution testing with disintegration
      testing, the mentioned criteria are not globally accepted. This study provides
      scientific justification for using disintegration testing rather than dissolution
      testing as a quality control method for certain immediate release (IR)
      formulations. A mechanistic approach, which is beyond the current FDA criteria,
      is presented. Dissolution testing via United States Pharmacopeial Convention
      Apparatus II at various paddle speeds was performed for immediate and extended
      release formulations of metronidazole. Dissolution profile fitting via DDSolver
      and dissolution profile predictions via DDDPlusTM were performed. The results
      showed that Fickian diffusion and drug particle properties (DPP) were responsible
      for the dissolution of the IR tablets, and that formulation factors (eg, coning)
      impacted dissolution only at lower rotation speeds. Dissolution was completely
      formulation controlled if extended release tablets were tested and DPP were not
      important. To demonstrate that disintegration is the most important dosage form
      attribute when dissolution is DPP controlled, disintegration, intrinsic
      dissolution and dissolution testing were performed in conventional and
      disintegration impacting media (DIM). Tablet disintegration was affected by DIM
      and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the
      formulation in DIM. DDDPlus was able to predict tablet dissolution and the
      intrinsic dissolution profiles in conventional media and DIM. The study showed
      that disintegration has to occur before DPP-dependent dissolution can happen. The
      study suggests that disintegration can be used as performance test of rapidly
      disintegrating tablets beyond the FDA criteria. The scientific criteria and
      justification is that dissolution has to be DPP dependent, originated from active
      pharmaceutical ingredient characteristics and formulations factors have to be
      negligible.

PMID- 28442891
TI  - Spotlight on nivolumab in the treatment of renal cell carcinoma: design,
      development, and place in therapy.
AB  - Several tyrosine kinase inhibitors targeting the vascular endothelial growth
      factor receptors and molecules inhibiting the mammalian target of rapamycin are
      being used for management of metastatic renal cell carcinoma (mRCC); however,
      there is still a potential for improvement. Immune checkpoint inhibitors like
      nivolumab and other PD-1/PD-L1 inhibitors provide an alternative approach for
      patients with mRCC. In this article, the authors review the safety profile and
      outcomes of phase 1, 2, and 3 clinical trials of nivolumab in mRCC.

PMID- 28442892
TI  - Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to
      the conventional film-coated 100 mg tablet administered to healthy male
      volunteers.
AB  - A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor,
      sildenafil, has been developed to examine the advantages of an orally
      disintegrating film formulation and provide an alternative to the current
      marketed products for the treatment of erectile dysfunction. The pharmacokinetics
      of the sildenafil 100 mg orodispersible film (IBSA) was compared to that of the
      conventional marketed 100 mg film-coated tablet (Viagra(r)) after single-dose
      administration to 53 healthy male volunteers (aged 18-51 years) in a randomized,
      open, two-way crossover bioequivalence study. Each subject received a single oral
      dose of 100 mg of sildenafil as test or reference formulation administered under
      fasting conditions at each of the two study periods according to a randomized
      crossover design. There was a washout interval of >=7 days between the two
      administrations of the investigational medicinal products. Blood samples for
      pharmacokinetic analysis were collected up to 24 h post-dosing. The primary
      objective was to compare the rate (peak plasma concentration; Cmax) and extent
      (area under the curve [AUC] from administration to last observed concentration
      time; AUC0-t) of sildenafil absorption after single-dose administration of test
      and reference. Secondary endpoints were observed to describe the plasma
      pharmacokinetic profiles of sildenafil and its metabolite N-desmethyl-sildenafil
      relative bioavailability and safety profile after single-dose administration. The
      mean sildenafil and N-desmethyl-sildenafil plasma concentration-time profiles up
      to 24 h after single-dose administration of sildenafil 100 mg orodispersible film
      and film-coated tablet were nearly superimposable. The bioequivalence test was
      fully satisfied for sildenafil and N-desmethyl-sildenafil in terms of rate and
      extent of bioavailability. Adverse events occurred at similar rates for the two
      formulations and were of mild-to-moderate severity. The results suggest that the
      new orodispersible film formulation can be used interchangeably with the
      conventional film-coated formulation.

PMID- 28442893
TI  - Vitamin D deficiency and tuberculosis: what about body mass index?

PMID- 28442894
TI  - Effect of adherence on daytime sleepiness, fatigue, depression and sleep quality
      in the obstructive sleep apnea/hypopnea syndrome patients undertaking nasal
      continuous positive airway pressure therapy.
AB  - OBJECTIVES: The aims of this study were to describe changes in day- and nighttime
      symptoms and the adherence to nasal continuous positive airway pressure (nCPAP)
      during the first 3-month nCPAP therapy among newly diagnosed patients with
      obstructive sleep apnea/hypopnea syndrome (OSAS) and to identify the effect of
      adherence on the changes in day- and nighttime symptoms during the first 3
      months. METHODS: Newly diagnosed OSAS patients were consecutively recruited from
      March to August 2013. Baseline clinical information and measures of the Epworth
      Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Zung's Self-Rating
      Depression Scale (SDS) and the Pittsburgh Sleep Quality Index (PSQI) at baseline
      and the end of 3rd, 6th, 9th and 12th week of therapy were collected. Twelve
      weeks' adherence was calculated as the average of each 3-week period. Mixed model
      was used to explore the effect of adherence to nCPAP therapy on ESS, FSS, SDS and
      PSQI in each 3-week phase. RESULTS: Seventy-six patients completed the 12-week
      follow-up. The mixed-effects models showed that under the control of therapy
      phase adherence in the range of <4 hours per night, using nCPAP could
      independently improve daytime sleepiness, in terms of ESS (coefficient, [95%
      confidence interval] unit; -4.49 [-5.62, -3.36]). Adherence at 4-6 hours per
      night could independently improve all variables of day- and nighttime symptoms
      included in this study, namely ESS -6.69 (-7.40, -5.99), FSS -6.02 (-7.14, 
      4.91), SDS -2.40 (-2.95, -1.85) and PSQI -0.20 (-0.52, -0.12). Further
      improvement in symptoms could be achieved at >=6 hours per night using nCPAP,
      which was ESS -8.35 (-9.26, -7.44), FSS -10.30 (-11.78, -8.83), SDS -4.42 (-5.15,
      -3.68) and PSQI -0.40 (-0.82, -0.02). The interaction between adherence level and
      therapy phase was not significant in day- and nighttime symptoms. CONCLUSION: The
      effect of adherence on the above-mentioned symptoms is stable through the first 3
      months. Under the control of therapy phase, the nCPAP therapy effectively
      improves day- and nighttime symptoms with >=4 hours adherence, and the patients
      can achieve a further improvement with >=6 hours adherence.

PMID- 28442895
TI  - Oral health-related quality of life and prosthetic status of nursing home
      residents with or without dementia.
AB  - PURPOSE: The objective of this cross-sectional study was to evaluate the effect
      of prosthetic status on the oral health-related quality of life (OHRQoL) of
      nursing home residents with or without dementia. METHODS: The study was performed
      in 14 nursing homes across the federal state of Baden-Wurttemberg, Germany. All
      eligible participants were included, and general and medical information and
      information about their dental and prosthetic statuses were collected. The
      Geriatric Oral Health Assessment Index (GOHAI) was administered to evaluate
      OHRQoL. The Mini-Mental State Examination (MMSE) served to classify participants
      into living or not living with dementia according to the established cutoff value
      for dementia (MMSE <24). Parametric bivariate statistics and logistic regression
      models were used to analyze data at P<0.05. RESULTS: A total of 169 participants
      were included in this study. The mean age of the participants was 82.9 years. A
      total of some 70% of the sample was living with dementia. The mean GOHAI score
      along the sample was 49.1 (8.3), and 41% of the sample reported substantially
      compromised OHRQoL (GOHAI <50). OHRQoL was statistically similar for people with
      or without dementia (P=0.234); objective oral health was also similar in both
      groups (P>0.05). The number of teeth (odds ratio [OR]: 2.0), the type of
      prosthetic status (OR: 6.5), and denture-related treatment needs (OR: 2.4) were
      the major factors significantly affecting OHRQoL (P<0.05). CONCLUSION: The OHRQoL
      of elderly nursing home residents is substantially compromised. Several
      prosthetic treatment needs for residents living with or without dementia were
      identified. Edentulism without tooth replacement and having <5 teeth resulted in
      an increased risk of substantially compromised OHRQoL. Further studies should be
      conducted to determine whether improvements in prosthetic status can increase
      OHRQoL.

PMID- 28442896
TI  - Comparison of safety and outcomes of shock wave lithotripsy between elderly and
      non-elderly patients.
AB  - BACKGROUND: This study compared the clinical outcomes of extracorporeal shock
      wave lithotripsy between elderly (aged $65 years) and non-elderly (aged <65
      years) patients. METHODS: A retrospective review of medical records was performed
      on 483 (non-elderly: 245, elderly: 238) patients with upper urinary tract stones
      who underwent shock wave lithotripsy between 2007 and 2015. The demographic data,
      stone parameters, stone-free rate, retreatment rate, and complication rate were
      analyzed in both elderly and non-elderly patient groups. RESULTS: There was no
      significant difference between non-elderly and elderly patients in terms of stone
      free rate (46.5% vs 41.1%, P>0.05) regardless of stone site or stone size and
      overall retreatment rate (41.6% vs 37.0%, P>0.05). Elderly patients had a higher
      complication rate than non-elderly patients (15.5% vs 23.5%, P=0.026). The most
      common complication was flank pain. Receiver operating characteristic curves
      predicted that elderly patients (cutoff value: 65 years of age) had a higher risk
      of complications and that patients with smaller stones (cutoff value: 0.8 cm) had
      a higher stone-free rate. CONCLUSION: This study showed that elderly patients
      with upper urinary tract stones undergoing shock wave lithotripsy had comparable
      efficacy for stone-free rates and retreatment rates, but higher complication
      rates.

PMID- 28442897
TI  - Cost-effectiveness analysis of oral versus intravenous drip infusion of
      levofloxacin in the treatment of acute lower respiratory tract infection in
      Chinese elderly patients.
AB  - AIM: Pharmacoeconomic cost-effectiveness analysis of two different dosage
      regimens of levofloxacin in the treatment of acute lower respiratory tract
      infection in elderly patients. METHODS: A total of 108 elderly patients with
      acute lower respiratory tract infection who visited by our hospital between
      September 2013 and September 2014 were randomly divided into Group A and Group B,
      with 54 patients in each group. In Group A, levofloxacin injection was given for
      continuous intravenous infusion treatment, whereas in Group B, levofloxacin
      injection and levofloxacin capsule were given as sequential therapy (ST). The
      period of treatment for both the groups was 10 days, and minimum cost analysis
      was used to analyze the treatment. RESULTS: Groups A and B had cure rates of
      61.1% and 59.3% (P>0.05), effective rates of 88.9% and 83.3% (P>0.05), bacterial
      clearance rates of 96.3% and 92.6% (P>0.05), and incidence rates of adverse
      reactions of 7.4% and 3.7% (P>0.05), respectively. Treatment costs of Groups A
      and B were 1,588 RMB and 1,150 RMB, respectively, whereas the cost-effectiveness
      of the two groups was at 17.86 and 13.81, respectively (P<0.05). CONCLUSION:
      Levofloxacin ST had relatively higher cost-effectiveness ratio for the treatment
      of acute lower respiratory tract infection in elderly patients, especially
      Chinese.

PMID- 28442898
TI  - Medication regimen complexity in ambulatory older adults with heart failure.
AB  - PURPOSE: Heart failure prevalence is increasing in older adults, and polypharmacy
      is a major problem in this population. We compared medication regimen complexity
      using the validated patient-level Medication Regimen Complexity Index (pMRCI)
      tool in "young-old" (60-74 years) versus "old-old" (75-89 years) patients with
      heart failure. We also compared pMRCI between patients with ischemic
      cardiomyopathy (ISCM) versus nonischemic cardiomyopathy (NISCM). PATIENTS AND
      METHODS: Medication lists were retrospectively abstracted from the electronic
      medical records of ambulatory patients aged 60-89 years with heart failure.
      Medications were categorized into three types - heart failure prescription
      medications, other prescription medications, and over-the-counter (OTC)
      medications - and scored using the pMRCI tool. RESULTS: The study evaluated 145
      patients (n=80 young-old, n=65 old-old, n=85 ISCM, n=60 NISCM, mean age 73+/-7
      years, 64% men, 81% Caucasian). Mean total pMRCI scores (32.1+/-14.4, range 3-84)
      and total medication counts (13.3+/-4.8, range 2-30) were high for the entire
      cohort, of which 72% of patients were taking eleven or more total medications.
      Total and subtype pMRCI scores and medication counts did not differ significantly
      between the young-old and old-old groups, with the exception of OTC medication
      pMRCI score (6.2+/-4 young-old versus 7.8+/-5.8 old-old, P=0.04). With regard to
      heart failure etiology, total pMRCI scores and medication counts were
      significantly higher in patients with ISCM versus NISCM (pMRCI score 34.5+/-15.2
      versus 28.8+/-12.7, P=0.009; medication count 14.1+/-4.9 versus 12.2+/-4.5,
      P=0.008), which was largely driven by other prescription medications. CONCLUSION:
      Medication regimen complexity is high in older adults with heart failure, and
      differs based on heart failure etiology. Additional work is needed to address
      polypharmacy and to determine if medication regimen complexity influences
      adherence and clinical outcomes in this population.

PMID- 28442899
TI  - Approaches to drug therapy for COPD in Russia: a proposed therapeutic algorithm.
AB  - Until recently, there have been few clinical algorithms for the management of
      patients with COPD. Current evidence-based clinical management guidelines can
      appear to be complex, and they lack clear step-by-step instructions. For these
      reasons, we chose to create a simple and practical clinical algorithm for the
      management of patients with COPD, which would be applicable to real-world
      clinical practice, and which was based on clinical symptoms and spirometric
      parameters that would take into account the pathophysiological heterogeneity of
      COPD. This optimized algorithm has two main fields, one for nonspecialist
      treatment by primary care and general physicians and the other for treatment by
      specialized pulmonologists. Patients with COPD are treated with long-acting
      bronchodilators and short-acting drugs on a demand basis. If the forced
      expiratory volume in one second (FEV1) is >=50% of predicted and symptoms are
      mild, treatment with a single long-acting muscarinic antagonist or long-acting
      beta-agonist is proposed. When FEV1 is <50% of predicted and/or the COPD
      assessment test score is >=10, the use of combined bronchodilators is advised. If
      there is no response to treatment after three months, referral to a pulmonary
      specialist is recommended for pathophysiological endotyping: 1) eosinophilic
      endotype with peripheral blood or sputum eosinophilia >3%; 2) neutrophilic
      endotype with peripheral blood neutrophilia >60% or green sputum; or 3) pauci
      granulocytic endotype. It is hoped that this simple, optimized, step-by-step
      algorithm will help to individualize the treatment of COPD in real-world clinical
      practice. This algorithm has yet to be evaluated prospectively or by comparison
      with other COPD management algorithms, including its effects on patient treatment
      outcomes. However, it is hoped that this algorithm may be useful in daily
      clinical practice for physicians treating patients with COPD in Russia.

PMID- 28442900
TI  - Identification of subtypes in subjects with mild-to-moderate airflow limitation
      and its clinical and socioeconomic implications.
AB  - PURPOSE: The purpose of this study was to identify subtypes in patients with mild
      to-moderate airflow limitation and to appreciate their clinical and socioeconomic
      implications. METHODS: Subjects who were aged >=20 years and had forced
      expiratory volume in 1 second (FEV1) >=60% predicted and FEV1/forced vital
      capacity <0.7 were selected from the fourth Korea National Health and Nutrition
      Examination Survey (KNHANES) in 2007-2012. The data were merged to the National
      Health Insurance reimbursement database during the same period. k-Means
      clustering was performed to explore subtypes. For clustering analysis, six key
      input variables - age, body mass index (BMI), FEV1% predicted, the presence or
      absence of self-reported wheezing, smoking status, and pack-years of smoking -
      were selected. RESULTS: Among a total of 2,140 subjects, five groups were
      identified through k-means clustering, namely putative "near-normal (n=232),"
      "asthmatic (n=392)," "chronic obstructive pulmonary disease (COPD) (n=37),"
      "asthmatic-overlap (n=893)," and "COPD-overlap (n=586)" subtypes. Near-normal
      group showed the oldest mean age (72+/-7 years) and highest FEV1 (102%+/-8%
      predicted), and asthmatic group was the youngest (46+/-9 years). COPD and COPD
      overlap groups were male predominant and all current or ex-smokers. While
      asthmatic group had the lowest prescription rate despite the highest proportion
      of self-reported wheezing, COPD, asthmatic-overlap, and COPD-overlap groups
      showed high prescription rate of respiratory medicine. Although COPD group formed
      only 1.7% of total subjects, they showed the highest mean medical cost and health
      care utilization, comprising 5.3% of the total medical cost. When calculating a
      ratio of total medical expense to household income, the mean ratio was highest in
      the COPD group. CONCLUSION: Clinical and epidemiological heterogeneities of
      subjects with mild-to-moderate airflow limitation and a different level of health
      care utilization by each subtype are shown. Identification of a subtype with high
      health care demand could be a priority for effective utilization of limited
      resources.

PMID- 28442901
TI  - Characteristics of COPD patients initiating treatment with aclidinium or
      tiotropium in primary care in Catalonia: a population-based study.
AB  - OBJECTIVE: To describe and compare demographic and clinical profile of patients
      newly initiated on aclidinium (ACL) or tiotropium (TIO) and identify factors
      associated with newly initiated ACL in real-life clinical practice during 2013 in
      Catalonia. DESIGN: We performed a population-based, retrospective, observational
      study with data obtained from the Information System for Research Development in
      Primary Care, a population database that contains information of 5.8 million
      inhabitants (more than 80% of the Catalan population). Patients over 40 years
      old, with a recorded diagnosis of COPD and newly initiated treatment with either
      ACL or TIO during the study period (January to December 2013), were selected. A
      descriptive analysis of demographic and clinical characteristics was performed,
      and treatment adherence was also assessed for both cohorts. RESULTS: A total of
      8,863 individuals were identified, 4,293 initiated with ACL and 4,570 with TIO.
      They had a mean age of 69.4 years (standard deviation: 11.3), a median COPD
      duration of 3 years (interquartile range: 0-8), and 71% were males. Patients
      treated with ACL were older, with more respiratory comorbidities, a longer time
      since COPD diagnosis, worse forced expiratory volume in 1 second (% predicted),
      and with a higher rate of exacerbations during the previous year compared with
      TIO. It was found that 41.3% of patients with ACL and 62.3% of patients with TIO
      had no previous COPD treatment. Inhaled corticosteroid and long-acting beta2
      agonist were the most frequent concomitant medications (32.9% and 32.6%,
      respectively). Approximately 75% of patients were persistent with ACL or TIO at 3
      months from the beginning of treatment, and more than 50% of patients remained
      persistent at 9 months. CONCLUSION: Patients initiated with ACL had more severe
      COPD and were taking more concomitant respiratory medications than patients
      initiated with TIO. ACL was more frequently initiated as part of triple therapy,
      while TIO was more frequently initiated as monotherapy.

PMID- 28442902
TI  - Self-rated health aspects among persons living with chronic obstructive pulmonary
      disease.
AB  - PURPOSE: To describe a cohort of chronic obstructive pulmonary disease (COPD)
      patients and perform a within-group comparison regarding self-management
      activation, social provision, and health status. PATIENTS AND METHODS: A cross
      sectional survey including 116 persons. RESULTS: The sample comprised 65 men and
      38 women, mean age 69 years. Fourteen percent reported very high impact of COPD
      on their health; 19% had received pulmonary rehabilitation offers, 39% had been
      offered self-management education, and 64% had acute hospital admissions due to
      COPD complications in the past year. Persons with COPD Assessment Test (CAT)
      scores >=30 reported significantly poorer self-management activation and
      significantly lower social provision than those reporting CAT scores <30. Number
      of COPD years had no significant influence on COPD health care consultations or
      self-management activation. CONCLUSION: Persons with COPD reported decreasing
      social provision with increasing COPD years and poorer health status. Although
      COPD is a progressive disease, health status and self-management activation did
      not vary with number of COPD years. Those living with a very high COPD impact on
      health reported significantly lower self-management activation but fewer acute
      hospital admissions. PRACTICE IMPLICATIONS: COPD patients' need for pulmonary
      rehabilitation, self-management support, and social support should be assessed
      and appropriate services offered throughout the disease trajectory.

PMID- 28442904
TI  - Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer
      hyperthermia therapy.
AB  - Compounds that recognize and strongly bind to molecular targets are one of the
      cornerstones of modern pharmaceutics. Work has been ongoing for the past 25 years
      on the therapeutic use of aptamers, nucleic acid molecules, whose three
      dimensional structure is the result of interactions between complementary base
      pairs. The aptamers selection methods allow the oligonucleotides which bind the
      molecular target in its native environment to be quickly isolated from a large
      library of random oligonucleotides. The possibilities presented for aptamers in
      the field of targeted therapy require the application of effective carriers to
      counter the renal clearance effect and/or functional cargo to exert therapeutic
      action if the aptamer is only used as a targeting moiety. Lately, a material
      gaining ground in biomedical research is iron oxide particles, which exhibit a
      superparamagnetic characteristic at nanoscale levels. This allows the iron oxide
      nanoparticles to convert external magnetic energy into heat, a mechanism known as
      hyperthermy, and efficiently supports conventional oncological treatment. In this
      study, we describe an experimentally confirmed functional model of targeted
      anticancer hyperthermia therapy. Using the systematic evolution of ligands by
      exponential enrichment technique, we selected a DNA aptamer that specifically
      binds to the extracellular domain of recombinant fibroblast growth factor
      receptor type-1 (FGFR1) with a nanomolar dissociation constant. The chosen target
      plays an important role in many crucial cellular processes and is also considered
      a candidate protein that is involved in tumor initiation, survival and
      progression. Next, we combined the selected aptamer with iron oxide nanoparticles
      to produce aptamer superparamagnetic conjugates (ASCs). Finally, we found that
      targeted ASCs selectively destroy FGFR1-overexpressing human osteosarcoma cells
      U2OS upon magnetic field irradiation.

PMID- 28442903
TI  - Magnetic and pH dual-responsive mesoporous silica nanocomposites for effective
      and low-toxic photodynamic therapy.
AB  - Nonspecific targeting, large doses and phototoxicity severely hamper the clinical
      effect of photodynamic therapy (PDT). In this work, superparamagnetic Fe3O4
      mesoporous silica nanoparticles grafted by pH-responsive block polymer
      polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) were fabricated to load
      the model photosensitizer rose bengal (RB) in the aim of enhancing the efficiency
      of PDT. Compared to free RB, the nanocomposites (polyethylene glycol-b
      polyaspartate-modified rose bengal-loaded magnetic mesoporous silica [RB-MMSNs])
      could greatly enhance the cellular uptake due to their effective endocytosis by
      mouse melanoma B16 cell and exhibited higher induced apoptosis although with
      little dark toxicity. RB-MMSNs had little dark toxicity and even much could be
      facilitated by magnetic field in vitro. RB-MMSNs demonstrated 10 times induced
      apoptosis efficiency than that of free RB at the same RB concentration, both by
      cell counting kit-8 (CCK-8) result and apoptosis detection. Furthermore, RB-MMSNs
      mediated PDT in vivo on tumor-bearing mice showed steady physical targeting of RB
      MMSNs to the tumor site; tumor volumes were significantly reduced in the magnetic
      field with green light irradiation. More importantly, the survival time of tumor
      bearing mice treated with RB-MMSNs was much prolonged. Henceforth, polyethylene
      glycol-b-polyaspartate-modified magnetic mesoporous silica (MMSNs) probably have
      great potential in clinical cancer photodynamic treatment because of their
      effective and low-toxic performance as photosensitizers' vesicles.

PMID- 28442905
TI  - A strategy to minimize the sensing voltage drift error in a transistor biosensor
      with a nanoscale sensing gate.
AB  - An ion-sensitive field-effect transistor (ISFET) biosensor is thought to be the
      center of the next era of health diagnosis. However, questions are raised about
      its functions and reliability in liquid samples. Consequently, real-life clinical
      applications are few in number. In this study, we report a strategy to minimize
      the sensing signal drift error during bioanalyte detection in an ISFET biosensor.
      A nanoscale SnO2 thin film is used as a gate oxide layer (GOL), and the surface
      of the GOL is chemically modified for improving bioanalyte-specific binding and
      for reducing undesirable ion reactions in sample solutions. The ISFET biosensor
      with surface-modified GOL shows significantly reduced sensing signal error
      compared with an ISFET with bare GOL in both diluted and undiluted phosphate
      buffered saline solutions.

PMID- 28442906
TI  - A review of drug delivery systems based on nanotechnology and green chemistry:
      green nanomedicine.
AB  - This review discusses the impact of green and environmentally safe chemistry on
      the field of nanotechnology-driven drug delivery in a new field termed "green
      nanomedicine". Studies have shown that among many examples of green
      nanotechnology-driven drug delivery systems, those receiving the greatest amount
      of attention include nanometal particles, polymers, and biological materials.
      Furthermore, green nanodrug delivery systems based on environmentally safe
      chemical reactions or using natural biomaterials (such as plant extracts and
      microorganisms) are now producing innovative materials revolutionizing the field.
      In this review, the use of green chemistry design, synthesis, and application
      principles and eco-friendly synthesis techniques with low side effects are
      discussed. The review ends with a description of key future efforts that must
      ensue for this field to continue to grow.

PMID- 28442907
TI  - Synthesis of magnetic molecularly imprinted polymers with excellent
      biocompatibility for the selective separation and inhibition of testosterone in
      prostate cancer cells.
AB  - PURPOSE: Androgen plays an important role in the progression of prostate cancer.
      In the present study, novel magnetic molecularly imprinted polymers (MMIPs) with
      good biocompatibility were produced for the selective separation and inhibition
      of testosterone in prostate cancer cells. MATERIALS AND METHODS: MMIPs were
      prepared by using magnetic nanospheres, gelatin, and testosterone as the
      supporting materials, functional monomer, and the template molecule,
      respectively. The characterization of the resultant products was investigated by
      transmission electron microscopy, X-ray diffraction, and vibrating sample
      magnetometry. To test whether MMIPs can remove testosterone in biologic samples,
      human LNCaP (androgen-dependent) and C4-2 (androgen-independent) prostate cancer
      cells were selected as cell models. The translocation of androgen receptor (AR)
      was detected by immunofluorescence assay, and the expression of PSA mRNA was
      detected by real-time quantitative polymerase chain reaction analysis. Cell flow
      cytometry analysis was performed to detect cell cycle arrest. RESULTS: The
      synthesized nanomaterials (MMIPs) possessed high crystallinity, satisfactory
      superparamagnetic properties, and uniform imprinted shell, and exhibited high
      adsorption capacity, fast kinetics, and high selectivity for testosterone.
      Moreover, the obtained imprinted nanomaterials could selectively enrich and
      detect testosterone in the LNCaP cell samples as a solid-phase extractant coupled
      with high-performance liquid chromatography. In addition, the MMIPs could freely
      enter prostate cancer cells and suppress the translocation of AR into the cell
      nucleus. We further found that MMIPs inhibited upregulation of AR downstream
      target genes in LNCaP and C4-2 cells; also, MMIPs inhibited cell growth and
      induced obvious cell cycle arrest in androgen-dependent LNCaP cells, but had no
      obvious effect on androgen-independent C4-2 cells. CONCLUSION: Our results
      indicate that the obtained imprinted nanomaterials can specifically and
      effectively bind testosterone and recover it from prostate cancer cells.
      Moreover, the MMIPs can freely enter prostate cancer cells and block the
      activation of testosterone-AR pathway. Thus, the MMIPs may be a new option for
      antiandrogen therapy in prostate cancer.

PMID- 28442908
TI  - Antibacterial activity and cytocompatibility of an implant coating consisting of
      TiO2 nanotubes combined with a GL13K antimicrobial peptide.
AB  - Prevention of implant-associated infections at an early stage of surgery is
      highly desirable for the long-term efficacy of implants in dentistry and
      orthopedics. Infection prophylaxis using conventional antibiotics is becoming
      less effective due to the development of bacteria resistant to multiple
      antibiotics. An ideal strategy to conquer bacterial infections is the local
      delivery of antibacterial agents. Therefore, antimicrobial peptide (AMP) eluting
      coatings on implant surfaces is a promising alternative. In this study, the
      feasibility of utilizing TiO2 nanotubes (TNTs), processed using anodization, as
      carriers to deliver a candidate AMP on titanium surfaces for the prevention of
      implant-associated infections is assessed. The broad-spectrum GL13K
      (GKIIKLKASLKLL-CONH2) AMP derived from human parotid secretory protein was
      selected and immobilized to TNTs using a simple soaking technique. Field emission
      scanning electron microscope, X-ray diffraction, Fourier transform infrared
      spectroscopy, and liquid chromatography-mass spectrometry analyses confirmed the
      successful immobilization of GL13K to anatase TNTs. The drug-loaded coatings
      demonstrated a sustained and slow drug release profile in vitro and eradicated
      the growth of Fusobacterium nucleatum and Porphyromonas gingivalis within 5 days
      of culture, as assessed by disk-diffusion assay. The GL13K-immobilized TNT (GL13K
      TNT) coating demonstrated greater biocompatibility, compared with a coating
      produced by incubating TNTs with equimolar concentrations of metronidazole. GL13K
      TNTs produced no observable cytotoxicity to preosteoblastic cells (MC3T3-E1). The
      coating may also have an immune regulatory effect, in support of rapid
      osseointegration around implants. Therefore, the combination of TNTs and AMP
      GL13K may achieve simultaneous antimicrobial and osteoconductive activities.

PMID- 28442909
TI  - Tat-functionalized liposomes for the treatment of meningitis: an in vitro study.
AB  - Bacterial meningitis has become a global concern, because of the emergence of
      antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter
      bacteria, thus providing a possible treatment for numerous infections, including
      meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse
      with the bacteria membrane and promote intracellular drug release. Moreover, this
      ability can be improved by using cell-penetrating peptides (such as Tat47-57,
      which is a peptide derived from the Tat protein of HIV). The purpose of this in
      vitro study was to demonstrate for the first time the ability of the presently
      prepared fusogenic liposomes, which were spherical particles with a diameter of
      100 nm loaded with antibiotics and functionalized with-cell penetrating peptides
      (Tat47-57), to fight the main bacteria that cause meningitis. For this,
      vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic
      liposomes to fight Streptococcus pneumoniae, methicillin-resistant Staphylococcus
      aureus, and Escherichia coli. Antibacterial activity of Tat-functionalized and
      nonfunctionalized liposomes loaded with antibiotics was tested by determining
      bacteria colony-forming units and growth-curve assays coupled with live/dead
      assays using fluorescence microscopy. Results showed a remarkable decrease in
      antibiotic minimum inhibitory concentration when all of the bacteria were treated
      with these novel liposomes, especially for the functionalized liposomes loaded
      with methicillin. With antibiotic concentrations of 1.7-3 ug/mL for Tat
      functionalized liposomes loaded with methicillin, the bacteria population was
      totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells,
      major cellular components of the blood-brain barrier, were also performed for all
      of the liposomes, including free antibiotic and the Tat peptide. Results showed
      much promise for the further study of the presently formulated liposomes to treat
      meningitis.

PMID- 28442910
TI  - Targeted delivery of thymosin beta 4 to the injured myocardium using CREKA
      conjugated nanoparticles.
AB  - PURPOSE: Thymosin beta 4 (Tbeta4) has multiple beneficial facets for myocardial
      injury, but its efficiency is limited by the low local concentration within the
      infarct. Here, we established a Tbeta4 delivery system for cardiac repair based
      on the interaction between the abundant fibrin in the infarct zone and the fibrin
      targeting moiety clot-binding peptide cysteine-arginine-glutamic acid-lysine
      alanine (CREKA). METHODS AND RESULTS: CREKA and Tbeta4 were conjugated to
      nanoparticles (CNP-Tbeta4). In vitro binding test revealed that CNP-Tbeta4 had a
      significant binding ability to the surface of fibrin clots when compared to the
      control clots (NP-Tbeta4). Based on the validation of fibrin expression in the
      early stage of ischemia injury, CNP-Tbeta4 was intravenously administered to mice
      with acute myocardial ischemia-reperfusion injury. CNP-Tbeta4 revealed a stronger
      fibrin-targeting ability than the NP-Tbeta4 group and accumulated mainly in the
      infarcted area and colocalized with fibrin. Subsequently, treatment with CNP
      Tbeta4 resulted in a better therapeutic effect. CONCLUSION: CRKEA modification
      favored Tbeta4 accumulation and retention in the infarcted region, leading to
      augmented functional benefits. Fibrin-targeting delivery system represents a
      generalizable platform technology for regenerative medicine.

PMID- 28442911
TI  - Are psychiatric comorbidities and associated cognitive functions related to
      treatment response to methylphenidate in boys with attention
      deficit/hyperactivity disorder?
AB  - BACKGROUND: Methylphenidate (MPH) has been found to be an effective medication
      for attention-deficit/hyperactivity disorder (ADHD). However, there are neither
      consistent nor sufficient findings on whether psychiatric comorbidities and
      associated cognitive functions of ADHD are related to treatment response to MPH
      in ADHD children. OBJECTIVES: This study investigated whether psychiatric
      comorbidities, IQ, and neurocognitive deficits are related to treatment response
      to MPH in ADHD children. In some ways, it is preferable to have a drug that the
      effectiveness of which to a disorder is not affected by its associated cognitive
      functions and psychiatric comorbidities. On the other hand, it is likely that the
      baseline symptom severity of ADHD is associated with the effectiveness of MPH
      treatment on the symptoms post treatment. METHODS: A total of 149 Chinese boys
      (aged 6-12 years) with ADHD, combined type, and normal IQ participated in this
      study. Assessment of ADHD symptom severity was conducted pre and post MPH
      treatment, while assessment of psychiatric comorbidities, IQ, and neurocognitive
      deficits was performed in a non-medicated condition. Treatment response was
      defined as the ADHD symptom severity post MPH treatment. RESULTS: Results
      indicated that MPH treatment was effective, significantly improving the ADHD
      condition. Yet, comorbid disorders, IQ, and neurocognitive deficits were not
      related to MPH treatment response on ADHD symptoms. These findings indicated that
      the effectiveness of MPH was not affected by psychiatric comorbidities and
      associated cognitive functions of ADHD. Instead, as expected, it was the baseline
      symptom severity that was mainly related to the treatment response, ie, the
      milder the baseline condition, the better the treatment response. CONCLUSION: The
      current findings positively endorse the widespread clinical use of MPH for
      treating ADHD. It improves the behavioral symptoms of ADHD regardless of varying
      psychiatric comorbidities, IQ, and neurocognitive deficits.

PMID- 28442912
TI  - Tumor necrosis factor-alpha and -beta genetic polymorphisms as a risk factor in
      Saudi patients with schizophrenia.
AB  - BACKGROUND: Schizophrenia is one of the most common devastating psychiatric
      disorders that negatively affects the quality of life and psychosocial functions.
      Its etiology involves the interplay of complex polygenic influences and
      environmental risk factors. Inflammatory markers are well-known etiological
      factors for psychiatric disorders, including schizophrenia. OBJECTIVE: The aim of
      this study was to investigate the association of proinflammatory cytokine genes,
      tumor necrosis factor (TNF)-alpha (-308G/A) and TNF-beta (+252A/G) polymorphisms
      with schizophrenia susceptibility. SUBJECTS AND METHODS: TNF-alpha and TNF-beta
      genes were amplified using amplification refractory mutation system primers in
      180 schizophrenia patients and 200 healthy matched controls recruited from the
      Psychiatry Clinic of Prince Sultan Military Medical City, Riyadh. The frequencies
      of alleles and genotypes of TNF-alpha (-308G/A) and TNF-beta (+252A/G)
      polymorphisms in patients were compared with those in controls. RESULTS: The
      frequencies of TNF-alpha (-308) allele A and genotype GA were significantly
      higher, while those of allele G and genotype GG were lower in schizophrenia
      patients as compared to controls, indicating that genotype GA and allele A of TNF
      alpha (-308G/A) may increase susceptibility to schizophrenia, while genotype GG
      and allele G may reduce it. On the other hand, the distribution of alleles and
      genotypes of TNF-beta (+252A/G) polymorphism does not differ significantly in
      patients from controls; however, the frequency of genotype GG of TNF-beta
      (+252A/G) was significantly higher in male patients than in female patients. The
      distribution of TNF-alpha (-308G/A) and TNF-beta (+252A/G) polymorphisms was
      almost similar in schizophrenia patients with negative or positive symptoms.
      CONCLUSION: TNF-alpha (-308G/A) and TNF-beta (+252G/A) polymorphisms may increase
      the susceptibility to schizophrenia in Saudi patients and could be a potential
      risk factor for its etiopathogenesis. However, further studies are warranted
      involving a larger sample size to strengthen our findings.

PMID- 28442914
TI  - Effectiveness of continuous improvement by a clinical pharmacist-led guidance
      team on the prophylactic antibiotics usage rationality in intervention procedure
      at a Chinese tertiary teaching hospital.
AB  - BACKGROUND: Irrational prophylactic antibiotics usage (PAU) during intervention
      procedures is common in China. A clinical pharmacist-led guidance team (CPGT) was
      established and participated in medical teams to advise on the rational usage of
      antibiotics. OBJECTIVES: The objective of this study was to assess the
      effectiveness of CPGT intervention for the rationality of PAU during intervention
      procedures. METHOD: This was a retrospective cross-sectional study with three
      stages at a Chinese tertiary teaching hospital. Patients who received some
      specific intervention procedures in the first quarter of 2015 were enrolled as
      the preintervention group, while those who received the procedures in the second
      and third quarters of 2015 were enrolled as the postintervention group. CPGT
      established the criteria for the PAU and conducted the intervention. The pre- and
      postintervention groups were then compared to evaluate the effectiveness of
      CPGTs' sustained interventions. RESULTS: A total of 651 patients were enrolled,
      with 200 patients in the preintervention group, while 233 patients and 218
      patients in the first- and second-intervention groups, respectively. With the
      implementation of CPGTs continuous intervention, the rationality of PAU was
      significantly improved, including the timing (91.98% vs 97.74%, P=0.015),
      duration (82.72% vs 98.31%, P<0.0001), and choice (81.48% vs 93.22%, P=0.001) of
      antibiotics administered during perioperative period. Moreover, the cost of total
      (US$34.89+/-80.96 vs US$9.81+/-26.31, P=0.025) and inappropriate PAU (US$28.75+/
      73.27 vs US$3.57+/-14.62, P<0.0001) per patient was significantly reduced.
      CONCLUSION: CPGTs' continuous intervention significantly improved the rationality
      of PAU during intervention procedures, with a significant reduction in antibiotic
      cost.

PMID- 28442913
TI  - Fracture risk in patients with type 2 diabetes mellitus and possible risk
      factors: a systematic review and meta-analysis.
AB  - AIM: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone
      fractures. A variable increase in fracture risk has been reported depending on
      skeletal site, diabetes duration, study design, insulin use, and so on. The
      present meta-analysis aimed to investigate the association between T2DM with
      fracture risk and possible risk factors. METHODS: Different databases including
      PubMed, Institute for Scientific Information, and Scopus were searched up to May
      2016. All epidemiologic studies on the association between T2DM and fracture risk
      were included. The relevant data obtained from these papers were analyzed by a
      random effects model and publication bias was assessed by funnel plot. All
      analyses were done by R software (version 3.2.1) and STATA (version 11.1).
      RESULTS: Thirty eligible studies were selected for the meta-analysis. We found a
      statistically significant positive association between T2DM and hip, vertebral,
      or foot fractures and no association between T2DM and wrist, proximal humerus, or
      ankle fractures. Overall, T2DM was associated with an increased risk of any
      fracture (summary relative risk =1.05, 95% confidence interval: 1.04, 1.06) and
      increased with age, duration of diabetes, and insulin therapy. CONCLUSION: Our
      findings strongly support an association between T2DM and increased risk of
      overall fracture. These findings emphasize the need for fracture prevention
      strategies in patients with diabetes.

PMID- 28442915
TI  - Efficacy and safety outcomes of sofosbuvir-based treatment regimens for hepatitis
      C virus-infected patients with or without cirrhosis from phase III clinical
      trials.
AB  - BACKGROUND: With the appearance of oral direct-acting antivirals (DAAs), the
      field of hepatitis C virus (HCV) treatment has been dramatically changed. This
      evolution makes possible for all oral treatments to be available for the
      treatment of HCV-infected patients. The aims of this review were to report the
      efficacy and safety of sofosbuvir (SOF)-based regimens for the treatment of
      patients with chronic HCV infection and to provide our clinical perspectives on
      these regimens. METHODS: A literature search of clinical studies published in
      PubMed and posted on ClinicalTrials.gov website was performed to identify studies
      evaluating the efficacy or safety of SOF-containing treatment regimens. RESULTS:
      A total of 23 clinical trials were examined in the review. The evaluated SOF
      based regimens are as follows: SOF/daclatasvir (DCV) +/- ribavirin (RBV),
      SOF/ledipasvir (LDV) +/- RBV, SOF/simeprevir (SMV), SOF/velpatasvir (VEL) +/-
      RBV, and SOF/RBV +/- peginterferon (peg-IFN). These SOF-based regimens were at
      least effective and safe for HCV-infected patients with or without cirrhosis. The
      SOF/VEL +/- RBV regimen, a pan-genotypic DAA regimen, was effective for the
      treatment of patients with HCV genotype 1, 2, 3, 4, 5, or 6 infection. The 24
      week SOF/RBV regimen was as effective as the 12-week SOF/RBV/peg-IFN regimen.
      Patients with HCV genotype 3 infection could have benefits from the use of the 24
      week SOF/RBV regimen. For cirrhotic patients with HCV genotype 3 infection, the
      12-week SOF/RBV/peg-IFN regimen could be considered as an alternative treatment
      option when access to SOF-based regimens with other DAAs is limited. In the
      included studies, significant adverse events due to SOF-based regimens were not
      reported. CONCLUSION: The clinical trials suggest that SOF-based treatment
      regimens for HCV-infected patients with or without cirrhosis can be at least
      effective and safe patient-convenient medications. However, it is necessary to
      monitor HCV-infected patients, since rare adverse events, drug-drug interactions,
      and drug-disease interactions can occur in real clinical settings.

PMID- 28442916
TI  - Expression and activity of the urokinase plasminogen activator system in canine
      primary brain tumors.
AB  - BACKGROUND: The expression of the urokinase plasminogen activator receptor
      (uPAR), a glycosylphosphatidylinositol-anchored protein family member, and the
      activity of its ligand, urokinase-type plasminogen activator (uPA), have been
      associated with the invasive and metastatic potentials of a variety of human
      brain tumors through their regulation of extracellular matrix degradation.
      Domesticated dogs develop naturally occurring brain tumors that share many
      clinical, phenotypic, molecular, and genetic features with their human
      counterparts, which has prompted the use of the dogs with spontaneous brain
      tumors as models to expedite the translation of novel brain tumor therapeutics to
      humans. There is currently little known regarding the role of the uPA system in
      canine brain tumorigenesis. The objective of this study was to characterize the
      expression of uPAR and the activity of uPA in canine brain tumors as
      justification for the development of uPAR-targeted brain tumor therapeutics in
      dogs. METHODS: We investigated the expression of uPAR in 37 primary canine brain
      tumors using immunohistochemistry, Western blotting, real-time quantitative
      polymerase chain reaction analyses, and by the assay of the activity of uPA using
      casein-plasminogen zymography. RESULTS: Expression of uPAR was observed in
      multiple tumoral microenvironmental niches, including neoplastic cells, stroma,
      and the vasculature of canine brain tumors. Relative to normal brain tissues,
      uPAR protein and mRNA expression were significantly greater in canine
      meningiomas, gliomas, and choroid plexus tumors. Increased activity of uPA was
      documented in all tumor types. CONCLUSIONS: uPAR is overexpressed and uPA
      activity increased in canine meningiomas, gliomas, and choroid plexus tumors.
      This study illustrates the potential of uPAR/uPA molecularly targeted approaches
      for canine brain tumor therapeutics and reinforces the translational significance
      of canines with spontaneous brain tumors as models for human disease.

PMID- 28442917
TI  - Can involved-field irradiation replace elective nodal irradiation in
      chemoradiotherapy for esophageal cancer? A systematic review and meta-analysis.
AB  - Chemoradiotherapy is the most common treatment for inoperable esophageal cancer.
      However, there is no consensus on the delineation of the clinical target volume.
      Elective nodal irradiation (ENI) is recommended for inoperable esophageal cancer.
      A few studies have reported a decrease in the incidence of radiation-related
      toxicity of involved-field irradiation (IFI) for esophageal cancer. A systematic
      review and pooled analysis were performed to determine whether IFI in definitive
      chemoradiotherapy was more beneficial than ENI for esophageal cancer. The results
      showed no significant differences in the overall survival and local control rates
      between the IFI and ENI arms. Meanwhile, the incidences of esophageal and lung
      toxicities were significantly decreased in the IFI arm. These results suggest
      that IFI is a feasible treatment option for locally advanced esophageal cancer,
      especially to minimize irradiation-related toxicity.

PMID- 28442918
TI  - Targeting the PD-1 pathway in pediatric solid tumors and brain tumors.
AB  - While remarkable advances have been made in the treatment of pediatric leukemia
      over the past decades, new therapies are needed for children with advanced solid
      tumors and high-grade brain tumors who fail standard chemotherapy regimens.
      Immunotherapy with immune checkpoint inhibitors acting through the programmed
      cell death-1 (PD-1) pathway has shown efficacy in some chemotherapy-resistant
      adult cancers, generating interest that these agents may also be helpful to treat
      certain refractory pediatric malignancies. In this manuscript we review current
      strategies for targeting the PD-1 pathway, highlighting putative biomarkers and
      the rationale for investigation of these drugs to treat common pediatric tumors
      such as sarcoma, neuroblastoma, and high-grade glioma. We summarize the completed
      and ongoing clinical trial data available, and suggest potential applications for
      further study.

PMID- 28442919
TI  - Gastric cancer, nutritional status, and outcome.
AB  - BACKGROUND: We aim to investigate the prognostic value of several nutrition-based
      indices, including the prognostic nutritional index (PNI), performance status,
      body mass index, serum albumin, and preoperative body weight loss in patients
      with gastric cancer (GC). MATERIALS AND METHODS: We retrospectively analyzed the
      records of 1,330 consecutive patients with GC undergoing curative surgery between
      October 2000 and September 2012. The relationship between nutrition-based indices
      and overall survival (OS) was examined using Kaplan-Meier analysis and Cox
      regression model. RESULTS: Following multivariate analysis, the PNI and
      preoperative body weight loss were the only nutritional-based indices
      independently associated with OS (hazard ratio [HR]: 1.356, 95% confidence
      interval [CI]: 1.051-1.748, P=0.019; HR: 1.152, 95% CI: 1.014-1.310, P=0.030,
      retrospectively). In stage-stratified analysis, multivariate analysis revealed
      that preoperative body weight loss was identified as an independent prognostic
      factor only in patients with stage III GC (HR: 1.223, 95% CI: 1.065-1.405,
      P=0.004), while the prognostic significance of PNI was not significant (all
      P>0.05). In patients with stage III GC, preoperative body weight loss stratified
      5-year OS from 41.1% to 26.5%. When stratified by adjuvant chemotherapy, the
      prognostic significance of preoperative body weight loss was maintained in
      patients treated with surgery plus adjuvant chemotherapy and in patients treated
      with surgery alone (P<0.001; P=0.003). CONCLUSION: Preoperative body weight loss
      is an independent prognostic factor for OS in patients with GC, especially in
      stage III disease. Preoperative body weight loss appears to be a superior
      predictor of outcome compared with other established nutrition-based indices.

PMID- 28442920
TI  - A blockade of PD-L1 produced antitumor and antimetastatic effects in an
      orthotopic mouse pancreatic cancer model via the PI3K/Akt/mTOR signaling pathway.
AB  - BACKGROUND: Pancreatic cancer is one of the most aggressive and intractable
      malignant tumors, and most deaths from pancreatic cancer are related to
      metastases. It has been demonstrated in vitro that overexpression of programmed
      death-ligand 1 (PD-L1) correlates with a lack of phosphatase and tensin homologue
      (PTEN) expression in pancreatic cancer tissue. This loss of PTEN expression may
      aberrantly activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target
      of rapamycin (mTOR) pathway, and thereby promote tumor cell survival,
      proliferation, and disease progression. In this study, we investigated the
      potential therapeutic effect of blockading PD-L1 expression on the progression of
      pancreatic cancer and its spontaneous liver metastases in vivo by inhibiting the
      PI3K/Akt/mTOR signaling pathway. METHODS: We investigated the effect of
      blockading PD-L1 in an orthotopic pancreatic cancer mouse model. The pancreatic
      tumor weights and inhibition ratios were determined after treatment with
      antimouse PD-L1 antibody for 5 weeks. We used immunohistochemistry methods to
      investigate PD-L1 expression in pancreatic cancer tissue and spontaneous liver
      metastasis tissue. The levels of mRNA and protein expression for various
      components involved in the PI3K/Akt/mTOR signaling pathway as well as for matrix
      metalloproteinases-2 and -9 (MMP2 and MMP9) were measured by reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot methods,
      respectively. RESULTS: Blockading PD-L1 significantly inhibited tumor growth and
      decreased the levels of PD-L1 expression in tumor tissue. Furthermore, the levels
      of PTEN mRNA and protein expression were elevated, while the levels of phospho
      Akt (p-Akt) and phospho-mTOR (p-mTOR) protein were decreased in pancreatic cancer
      and liver metastasis tissues after establishing a PD-L1 blockade. In addition, a
      PD-L1 blockade decreased the levels of MMP2 and MMP9 mRNA and protein expression
      in tumor tissues. CONCLUSION: Our results suggest that a blockade of PD-L1 may
      inhibit the growth and metastasis of pancreatic cancer by modulating the
      PI3K/Akt/mTOR pathway.

PMID- 28442921
TI  - miR-762 can negatively regulate menin in ovarian cancer.
AB  - Ovarian cancer accounts for the major part of the mortality attributable to
      female reproductive system malignant tumors worldwide. Recently, the incidence of
      ovarian cancer has been increasing annually, and there remains a lack of suitable
      treatment methods that can significantly improve the 5-year survival rates of
      patients. Therefore, it is necessary to identify more effective treatments for
      ovarian cancer. It is established that microRNAs (miRNAs) have important roles in
      the diagnosis and treatment of ovarian cancer and a specific miRNA, miR-762, can
      promote the development of a variety of tumors. Menin is encoded by MEN1, a tumor
      suppressor gene, that is usually downregulated in ovarian cancer. In this study,
      we evaluated the expression levels of miR-762 and menin in ovarian cancer tissues
      and demonstrated that they were correlated. In addition, we found that miR-762
      can downregulate the expression of menin through a binding site in its 3'-UTR and
      consequently upregulate the Wnt cell signaling pathway to promote the development
      of ovarian cancer. These results indicate that miR-762 is a promising potential
      target for the treatment of ovarian cancer.

PMID- 28442922
TI  - Inhibition of PCSK9 protects against radiation-induced damage of prostate cancer
      cells.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein
      expressed primarily in the liver, formerly known to maintain plasma lipid
      homeostasis by regulating low-density lipoprotein receptor levels, and its exact
      role in the radioresistance of prostate cancer (PCa) remains unclear. We aim to
      investigate the function of PCSK9 in the radioresistance of PCa cells. METHODS:
      PCSK9 small interfering RNA (siRNA) was introduced into the PCa cells by
      transient transfection. Then, cells were exposed to ionizing radiation (IR) at
      indicated dose rates. Cell damage was detected using cell counting kit-8 (CCK-8)
      and Hoechest 33342/propidium iodide (PI) staining. Rhodamine-123 (Rho-123) dye
      was used to assay mitochondrial membrane potential alteration. Western blot was
      used to detect the apoptosis-related protein expression. RESULTS: PCSK9 siRNA
      treatment significantly protected PCa cells from IR-induced cell damage,
      including enhancing cell viability, reducing apoptosis, and inhibiting MMPs.
      Moreover, PCSK9 siRNA repressed the increase of cytochrome C (cyto C), caspase-3,
      and B-cell leukemia/lymphoma 2 (Bcl-2)-associated X (Bax) expressions induced by
      IR and promoted Bcl-2 expression, which might partially interpret the
      radioprotective role of PCSK9 siRNA in PCa cells. CONCLUSION: PCSK9 might impact
      on radiosensitivity through mitochondrial pathways and serve as a novel
      therapeutic target for PCa patients.

PMID- 28442923
TI  - Soluble cytotoxic T-lymphocyte antigen 4: a favorable predictor in malignant
      tumors after therapy.
AB  - PURPOSE: Soluble cytotoxic T-lymphocyte antigen 4 (sCTLA-4), one of the isoforms
      of CTLA-4, was discovered to be critical in downregulating the negative signal of
      CTLA-4 in T-cell responses. Contrary to the classical immunosuppressive effect of
      CTLA-4, its immunoregulatory function might be complicated. However, the clinical
      significance of sCTLA-4 to immune regulation and the variation in cancer therapy
      have not been elucidated. We postulated that the level of sCTLA-4 might affect
      the outcome of cancer prognosis. PATIENTS AND METHODS: Serum concentrations of
      sCTLA-4 before and after therapy in 141 locally advanced and advanced cancer
      patients were measured and survival analyses was performed. Hazard ratio and 95%
      confidence interval for overall survival (OS) were calculated. Cutoffs were
      determined by median across the sCTLA-4 level of entire patients. RESULTS: High
      expression of sCTLA-4 after therapy indicated significant longer OS and
      progression-free survival (PFS) (all P<0.01). Among all subgroups, sCTLA-4 levels
      after therapies were found to be significantly higher than that of 1 day before,
      which was also negatively correlated with tumor node metastasis stage and lymph
      node metastasis (all P<0.05). Multivariate analysis revealed that sCTLA-4 level
      was a strong independent prognostic factor for OS and PFS (all P<0.05).
      CONCLUSION: Our data demonstrated the favorable prognostic significance of sCTLA
      4 and may lead to the development of new immunotherapy options for cancer
      patients.

PMID- 28442924
TI  - A framework for measuring self-management effectiveness and health care use among
      pediatric asthma patients and families.
AB  - Asthma is associated with substantial health care expenditures, including an
      estimated US$56 billion per year in direct costs. A recurring theme in the asthma
      management literature is that costly asthma symptoms, including hospitalizations
      and multiple emergency department (ED)/outpatient visits, can often be prevented
      through patient/family adherence to the national (National Institutes of Health
      Expert Panel Report-3) guidelines for effective self-management of asthma,
      specifically 1) medication adherence and 2) environmental trigger avoidance, as
      outlined in the patient's personalized Asthma-Action Plan. It is important to
      note however that while effective self-management of asthma is known to reduce ED
      visits and hospitalizations, the relationship between asthma self-management
      effectiveness and outpatient visit frequency remains ambiguous, reflecting a gap
      in the literature. For instance, do patients/families who self-manage effectively
      visit outpatient clinics more frequently for asthma care (compared to those who
      do not self-manage effectively), after accounting for differences in asthma
      severity, demographic characteristics, and risk factors? Do patients/families who
      visit outpatient clinics more frequently for asthma care, in turn have fewer ED
      and inpatient encounters for asthma? On the other hand, do patients/families who
      do not revisit outpatient clinics regularly have higher ED visits and
      hospitalizations? It is important to address these gaps, in order to reduce the
      costs and public health burden of asthma. This paper provides a foundation for
      addressing these gaps, by conducting an integrative review of the asthma
      management literature, to develop a conceptual framework for measuring self
      management effectiveness and health care use among pediatric asthma
      patients/families. In doing so, the paper lays the groundwork for future research
      seeking to explicate the relationship between asthma self-management
      effectiveness and health care use, which in turn has potential to engage asthma
      providers in promoting ideal self-management and optimal health care use for
      pediatric asthma, in accordance with national evidence-based guidelines for
      asthma management.

PMID- 28442925
TI  - CYP2C19 polymorphism frequency in Russian patients in Central Russia and Siberia
      with acute coronary syndrome.
AB  - PURPOSE: The aim of this study is to investigate the frequency of CYP2C19*2, *3
      allelic variants, associated with poor response to clopidogrel, and CYP2C19*17,
      associated with excessive response to clopidogrel, in patients with acute
      coronary syndrome (ACS) from Siberia and Moscow regions of Russia. PATIENTS AND
      METHODS: The study included 512 ACS patients who were subsequently treated with
      coronary arterial stenting. The subjects assigned were from the cities of Central
      (Novosibirsk, Kemerovo), Eastern (Irkutsk), Northern (Surgut) Siberia regions and
      from Moscow region. The mean age of patients enrolled was 63.9+/-10.9 years.
      Among the assigned subjects, the proportion of men accounted for 80% and women
      20%. RESULTS: According to the results obtained in the present study, from 16% up
      to 27.5% of patients in different regions of Russia have at least one CYP2C19
      "poor metabolizer" (PM) allele variant affecting clopidogrel metabolism and,
      therefore, suppressing its antiplatelet activity. CYP2C19*17 allele variant was
      identified with the frequency of 15.4% up to 33.3%. The study revealed the
      presence of statistically significant differences in CYP2C19*3 allele frequency
      between the Russian ethnic group patients from Eastern and Central Siberia
      (p=0.001; odds ratio=1.05 [95% confidence interval 1.01-1.09]). CONCLUSION: The
      study revealed statistically significant differences between the allele
      frequencies in Eastern and Central Siberia, which can probably be caused by a
      considerable number of Buryats inhabiting Eastern Siberia.

PMID- 28442926
TI  - Hypothermia due to limbic system involvement and longitudinal myelitis in a case
      of Japanese encephalitis: a case report from India.
AB  - Japanese encephalitis (JE) is an infectious encephalitis prevalent in Asia. It
      usually presents with fever, headache, convulsions and extrapyramidal symptoms.
      Limbic system involvement and hypothermia though common in autoimmune
      encephalitis have never been reported in JE. We report a case of an 18-year-old
      girl with no previous comorbidities who presented to us with a history of fever
      and headache for 1 week duration. She developed bilateral lateral rectus palsy
      and asymmetric flaccid weakness of all four limbs, after 2 days of admission,
      which was followed by altered sensorium and intermittent hypothermia.
      Neuroimaging revealed longitudinal myelitis extending from pons till the L1 level
      along with bilateral thalamic hemorrhage in brain. Cerebrospinal fluid (CSF) was
      positive for IgM antibody to JE virus. She was treated with supportive measures,
      but she developed intractable hypothermia and seizures and succumbed to illness
      after 2 weeks of admission.

PMID- 28442928
TI  - The efficacy and safety of S-flurbiprofen plaster in the treatment of knee
      osteoarthritis: a phase II, randomized, double-blind, placebo-controlled, dose
      finding study.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) patches are convenient
      for use and show much less gastrointestinal side effects than oral NSAIDs,
      whereas its percutaneous absorption is not sufficient for the expression of
      clinical efficacy at satisfactory level. S-flurbiprofen plaster (SFPP) has shown
      dramatic improvement in percutaneous absorption results from animal and clinical
      studies. In this study, the efficacy and safety of SFPP were compared with
      placebo in patients with knee osteoarthritis (OA) to determine its optimal dose.
      This was a multicenter, randomized, double-blind, parallel-group comparative
      study. PATIENTS AND METHODS: Enrolled 509 knee OA patients were treated with
      placebo or SFPP at 10, 20, or 40 mg applied on the affected site once daily for 2
      weeks. The primary endpoint for efficacy was improvement in knee pain on rising
      from the chair assessed by visual analog scale (VAS). The other endpoints were
      clinical symptoms, pain on walking, and global assessment by both investigator
      and patient. Safety was evaluated by observing adverse events (AEs). RESULTS: VAS
      change in knee pain from baseline to trial end was dose-dependent, least squares
      mean was 29.5, 31.5, 32.0, and 35.6 mm in placebo and SFPP 10, 20, and 40 mg,
      respectively. A significant difference was observed between placebo and SFPP 40
      mg (P=0.001). In contrast, the effect of SFPP at a dose <=20 mg was not
      significantly different from that of placebo. The proportion of the patients who
      achieved 50% pain relief was 72.4% in 40 mg and 51.2% in placebo (P<0.001). In
      all other endpoints, SFPP 40 mg showed significant improvement compared with
      placebo. The incidence of AEs was not different across all four groups, and no
      severe AEs were observed. CONCLUSION: Clinically relevant pain relief was
      observed in all groups including placebo. Especially 40 mg showed remarkable pain
      relief in not only primary endpoint but also all the other endpoint with
      significant differences over placebo. The safety profile of SFPP 40 mg was not
      different from that of placebo. Therefore, 40 mg was determined as the optimal
      tested dose.

PMID- 28442927
TI  - Mechanical factors and vitamin D deficiency in schoolchildren with low back pain:
      biochemical and cross-sectional survey analysis.
AB  - OBJECTIVE: This study was designed to evaluate the role of vitamin D, muscle
      fatigue biomarkers, and mechanical factors in the progression of low back pain
      (LBP) in schoolchildren. BACKGROUND: Children and adolescents frequently suffer
      from LBP with no clear clinical causes, and >71% of schoolchildren aged 12-17
      years will show at least one episode of LBP. MATERIALS AND METHODS: A total of
      250 schoolchildren aged 12-16 years were randomly enrolled in this study. For all
      schoolchildren height, weight, percentage of daily sun exposure and and areas of
      skin exposed to sun, method of carrying the bag, and bag weight and type were
      recorded over a typical school week. Pain scores, physical activity (PA), LBP,
      serum vitamin 25(OH)D level, serum bone-specific alkaline phosphatase, creatine
      kinase (CK), and lactate dehydrogenase (LDH) activities and calcium (Ca)
      concentrations were estimated using prevalidated Pain Rating Scale, modified
      Oswestry Low Back Pain Disability Questionnaire, short-form PA questionnaire, and
      colorimetric and immunoassay techniques. RESULTS: During the period of October
      2013-May 2014, LBP was estimated in 52.2% of the schoolchildren. It was
      classified into moderate (34%) and severe (18%). Girls showed a higher LBP (36%)
      compared with boys (24%). In schoolchildren with moderate and severe LBP
      significantly higher (P=0.01) body mass index, waist, hip, and waist-to-hip ratio
      measurements were observed compared with normal schoolchildren. LBP significantly
      correlated with less sun exposure, lower PA, sedentary activity (TV/computer
      use), and overloaded school bags. In addition, schoolchildren with severe LBP
      showed lower levels of vitamin 25(OH)D and Ca and higher levels of CK, LDH, and
      serum bone-specific alkaline phosphatase compared with moderate and healthy
      schoolchildren. Stepwise regression analysis revealed that age, gender,
      demographic parameters, PA, vitamin D levels, Ca, CK, and LDH associated with
      ~56.8%-86.7% of the incidence of LBP among schoolchildren. CONCLUSION: In
      children and adolescents, LBP was shown to be linked with limited sun exposure,
      inadequate vitamin D diets, adiposity, lower PA, sedentary lifestyles, vitamin 25
      (OH) D deficiency, and lower levels of Ca, CK, and LDH.

PMID- 28442929
TI  - An evaluation of two different methods of coccygectomy in patients with traumatic
      coccydynia.
AB  - PURPOSE: The aim of this study was to evaluate the results of partial and total
      coccyx excisions in patients with traumatic coccydynia resistant to conservative
      treatment. PATIENTS AND METHODS: The study included 22 patients (from a total of
      27) who underwent partial or total coccygectomy because of persistent coccydynia
      between December 2007 and January 2014. There were 15 females and 7 males with a
      mean age of 33.6 years (range 23-46 years). Partial coccygectomy was performed in
      14 patients and total coccygectomy in 8. They were evaluated according to their
      pre- and postoperative visual analog scale (VAS) scores. The mean follow-up
      period was 28 months (range 16-48 months). RESULTS: The mean VAS scores in the
      total excision group were 8.88+/-0.64 preoperatively and 2.5+/-2.67 at the final
      postoperative follow-up examination. In the partial excision group, these values
      were 8.79+/-0.89 preoperatively and 2.5+/-2.85 postoperatively. No statistically
      significant difference was determined between the two groups with respect to the
      mean scores (p>0.05). No rectum injury was seen in any patient. When the VAS
      scores of the patients were evaluated as a whole, excellent and good results were
      obtained in 78%. Patient satisfaction with the operation was 90%. CONCLUSION:
      Coccyx excision is a successful treatment method in patients with long-term
      coccydynia who are resistant to conservative treatment. Two different surgical
      methods can be applied in the treatment and both of them have low complication
      rates and high patient satisfaction.

PMID- 28442930
TI  - Thoracic epidural analgesia reduces myocardial injury in ischemic patients
      undergoing major abdominal cancer surgery.
AB  - BACKGROUND AND OBJECTIVES: Major abdominal cancer surgeries are associated with
      significant perioperative mortality and morbidity due to myocardial ischemia and
      infarction. This study examined the effect of perioperative patient controlled
      epidural analgesia (PCEA) on occurrence of ischemic cardiac injury in ischemic
      patients undergoing major abdominal cancer surgery. PATIENTS AND METHODS: One
      hundred and twenty patients (American Society of Anesthesiologists grade II and
      III) of either sex were scheduled for elective upper gastrointestinal cancer
      surgeries. Patients were allocated randomly into two groups (60 patients each) to
      receive, besides general anesthesia: continuous intra and postoperative
      intravenous (IV) infusion with fentanyl for 72 h postoperatively (patient
      controlled intravenous analgesia [PCIA] group) or continuous intra and
      postoperative epidural infusion with bupivacaine 0.125% and fentanyl (PCEA group)
      for 72 h postoperatively. Perioperative hemodynamics were recorded. Postoperative
      pain was assessed over 72 h using visual analog scale (VAS). All patients were
      screened for occurrence of myocardial injury (MI) by electrocardiography,
      echocardiography, and cardiac troponin I serum level. Other postoperative
      complications as arrhythmia, deep venous thrombosis (DVT), pulmonary embolism,
      pneumonia, and death were recorded. RESULTS: There was a significant reduction in
      overall adverse cardiac events (myocardial injury, arrhythmias, angina, heart
      failure and nonfatal cardiac arrest) in PCEA group in comparison to PCIA group.
      Also, there was a significant reduction in dynamic VAS pain score in group PCEA
      in comparison to PCIA at all measured time points. Regarding perioperative
      hemodynamics, there was a significant reduction in intra-operative mean arterial
      pressure (MAP); and heart rate in PCEA group in comparison to PCIA group at most
      of measured time points while there was not a significant reduction in
      postoperative MAP and heart rate in the second and third postoperative days. The
      incidence of other postoperative complications such as DVT, pneumonia and in
      hospital mortality were decreased in PCEA group. CONCLUSION: Perioperative
      thoracic epidural analgesia in patients suffering from coronary artery disease
      subjected to major abdominal cancer surgery reduced significantly postoperative
      major adverse cardiac events with better pain control in comparison with
      perioperative IV analgesia.

PMID- 28442931
TI  - Postoperative pain and patient-controlled epidural analgesia-related adverse
      effects in young and elderly patients: a retrospective analysis of 2,435
      patients.
AB  - In this retrospective study, data of 2,435 patients who received fentanyl and
      ropivacaine-based patient-controlled epidural analgesia (PCEA) for pain relief
      after elective surgery under general or spinal anesthesia were reviewed.
      Differences in postoperative pain, incidence of patient-controlled analgesia
      (PCA)-related adverse effects, and risk factors for the need for rescue
      analgesics for 48 hours postsurgery in young (age 20-39 years) and elderly (age
      >=70 years) patients were evaluated. Although there were no significant
      differences in postoperative pain intensity between the two groups until 6 hours
      postsurgery, younger patients experienced greater postoperative pain intensity
      compared with older patients 6-48 hours postsurgery. While younger patients
      exhibited greater incidence of numbness, motor weakness, and discontinuation of
      PCA postsurgery, elderly patients exhibited greater incidence of hypotension,
      nausea/vomiting, rescue analgesia, and antiemetic administration. Upon
      multivariate analysis, low fentanyl dosage and history of smoking were found to
      be associated with an increased need for rescue analgesia among younger patients,
      while physical status classification III/IV and thoracic surgery were associated
      with a decreased need for rescue analgesia among the elderly. Discontinuation of
      PCA was more frequent among younger patients than the elderly (18.5% vs 13.5%,
      P=0.001). Reasons for discontinuation of PCA among young and elderly patients,
      respectively, were nausea and vomiting (6.8% vs 26.6%), numbness or motor
      weakness (67.8% vs 11.5%), urinary retention (7.4% vs 8.7%), dizziness (2.2% vs
      5.2%), and hypotension (3.1% vs 20.3%). In conclusion, PCEA was more frequently
      associated with numbness, motor weakness, and discontinuation of PCA in younger
      patients and with hypotension, nausea/vomiting, and a greater need for rescue
      analgesics/antiemetics among elderly patients. Therefore, in order to minimize
      the adverse effects of PCEA and enhance pain relief, different PCEA regimens and
      administration/prevention strategies should be considered for young and elderly
      patients.

PMID- 28442932
TI  - Granular cell tumor in breast: a case report.
AB  - : Granular cell tumor (GCT) is a rare neoplasm of the soft tissues, and <1% of
      all GCTs are malignant. It usually appears in the tongue and sometimes may affect
      the female breast. Initially, GCT was considered to be a myogenic lesion
      affecting female breast (myoblastoma). Actually, it is assumed as a tumor
      originating from perineural or putative Schwann cells of peripheral nerves or
      their precursors that grows in the lobular breast tissue, due to the
      immunohistochemical features. Here, we review the importance of differentiating
      between this tumor and malignant breast carcinoma. Mammographically, by
      ultrasound scan and clinically, this case appears to be a malignant tumor of the
      breast, but with a correct and precise diagnosis including histopathologic
      examination and immunohistochemical studies, it was correctly identified as a
      GCT. CASE DETAILS: We present a case of a 52-year-old premenopausal woman. This
      report is of interest because of patient's familial oncologic history and
      personal history of gynecologic cancer. This rare tumor of the breast and the
      special way to approach the tumor by local anesthesia makes it interesting to
      communicate. CONCLUSION: This is a case of interest because GCT located in the
      breast is very unusual and knowledge of GCT is required for the differential
      diagnosis with breast cancer.

PMID- 28442934
TI  - Effect of glomerular filtration rate at dialysis initiation on survival in
      patients with advanced chronic kidney disease: what is the effect of lead-time
      bias?
AB  - PURPOSE: Current clinical guidelines recommend to initiate dialysis in the
      presence of symptoms or signs attributable to kidney failure, often with a
      glomerular filtration rate (GFR) of 5-10 mL/min/1.73 m2. Little evidence exists
      about the optimal kidney function to start dialysis. Thus far, most observational
      studies have been limited by lead-time bias. Only a few studies have accounted
      for lead-time bias, and showed contradictory results. We examined the effect of
      GFR at dialysis initiation on survival in chronic kidney disease patients, and
      the role of lead-time bias therein. We used both kidney function based on 24-hour
      urine collection (measured GFR [mGFR]) and estimated GFR (eGFR). MATERIALS AND
      METHODS: A total of 1,143 patients with eGFR data at dialysis initiation and 852
      patients with mGFR data were included from the NECOSAD cohort. Cox regression was
      used to adjust for potential confounders. To examine the effect of lead-time
      bias, survival was counted from the time of dialysis initiation or from a common
      starting point (GFR 20 mL/min/1.73 m2), using linear interpolation models.
      RESULTS: Without lead-time correction, no difference between early and late
      starters was present based on eGFR (hazard ratio [HR] 1.03, 95% confidence
      interval [CI] 0.81-1.3). However, after lead-time correction, early initiation
      showed a survival disadvantage (HR between 1.1 [95% CI 0.82-1.48] and 1.33 [95%
      CI 1.05-1.68]). Based on mGFR, the potential survival benefit for early starters
      without lead-time correction (HR 0.8, 95% CI 0.62-1.03) completely disappeared
      after lead-time correction (HR between 0.94 [95% CI 0.65-1.34] and 1.21 [95% CI
      0.95-1.56]). Dialysis start time differed about a year between early and late
      initiation. CONCLUSION: Lead-time bias is not only a methodological problem but
      also has clinical impact when assessing the optimal kidney function to start
      dialysis. Therefore, lead-time bias is extremely important to correct for. Taking
      account of lead-time bias, this controlled study showed that early dialysis
      initiation (eGFR >7.9, mGFR >6.6 mL/min/1.73 m2) was not associated with an
      improvement in survival. Based on kidney function, this study suggests that in
      some patients, dialysis could be started even later than an eGFR <5.7 and mGFR
      <4.3 mL/min/1.73 m2.

PMID- 28442933
TI  - Drainage of malignant ascites: patient selection and perspectives.
AB  - Malignant ascites (MA) is a sign of advanced cancer and poor prognosis. MA can
      result in impairment in quality of life (QOL) and significant symptoms. As a
      supportive treatment, ascites can be drained by paracentesis (PC), percutaneously
      implanted catheters (tunneled, untunneled, central venous catheters), or
      peritoneal ports, or peritoneovenous shunts. The aim of this study was to
      evaluate the effectiveness, safety, and patient-reported outcomes (PRO) of
      different drainage methods for the management of MA. A systematic review of the
      literature was performed, and 32 original articles met the inclusion criteria.
      Patients selected for permanent drain insertion demonstrated symptoms related to
      MA and had undergone repeated PC. The primary focus of the reviewed articles was
      procedural safety issues. The rate of technical success of drainage device
      installation was 100%. Most patients experienced improvements in symptom control
      after ascites drainage. When analyzed together, 19.7% (255/1297) of patients
      experienced any complication and 6.2% (81/1297) experienced serious adverse
      events during MA drainage. Complications were reported for every drainage method;
      however, the least occurred after PC or central venous catheter, while the most
      serious occurred after peritoneovenous shunts. Adverse events were as follows:
      catheter obstruction: 4.4%, infection: 4.1%, leakage: 3.5%, catheter dislodgment:
      2.3%, hypotension: 0.6%, injuries during device insertion: 0.6%, renal
      impairment: 0.5%, electrolyte imbalance: 0.2%, other: 3.6%. PRO and QOL endpoints
      were available for 12 studies. When PRO were measured using an interview, a
      significant improvement in symptom control and QOL was reported in almost all
      patients. Once standardized questionnaires were used, improvements in symptomatic
      scores and role functioning were observed. Deterioration was observed in
      cognitive and emotional subscales. MA drainage is a safe and effective method to
      control symptoms associated with ascites, and should be perceived as a supportive
      care, that can be applied for those who need it at any time of their cancer
      trajectory. Patient selection should be performed using a thorough assessment of
      symptoms and QOL, and should not be delayed.

PMID- 28442935
TI  - New developments in the treatment of hypoactive sexual desire disorder - a focus
      on Flibanserin.
AB  - The objective of the authors is to highlight the historical complexities for the
      diagnosis and treatment of hypoactive sexual desire disorder (HSDD) with a focus
      on Flibanserin. A systematic review of the medical literature published in PubMed
      using the search terms HSDD and Flibanserin was conducted. Each author reviewed
      the results of the systematic review for articles to include in this study. HSDD
      is defined as a persistent or recurrent deficiency or absence of sexual fantasies
      and desire for sexual activity causing marked distress or interpersonal
      difficulty that is not better accounted for by another diagnosis. Until 2015,
      only homeopathic products and off-label use of prescription medications were
      medical treatment options for women with HSDD. Flibanserin, approved by the US
      Food and Drug Administration (FDA) in 2015, is the first to target female HSDD in
      premenopausal women. Flibanserin is a centrally acting nonhormonal oral
      medication taken once daily that affects serotonin, dopamine and norepinephrine
      levels, the key neurotransmitters in the biology of desire. Understanding
      prescribing guidelines and awareness of black box warnings is paramount for
      prescribers. Adherence to proper oversight will ensure Flibanserin can fulfil an
      unmet need for an FDA approved prescription medication for the treatment of HSDD
      in premenopausal women.

PMID- 28442936
TI  - Factors influencing maternal mortality among rural communities in southwestern
      Nigeria.
AB  - BACKGROUND: Maternal mortality and morbidity reflect the status of population
      health and quality of life across nations. Poor understanding of the interplay of
      many antecedent factors, including sociocultural, economic and logistic factors,
      combined with an overwhelming poor health services delivery, is a basic challenge
      in several countries, particularly in rural settings where functional health care
      services are relatively scarce. There are still uncertainties as to the extent of
      this burden, owing to current challenges with information and data collation.
      This study aimed at identifying nonmedical factors associated with maternal
      mortality in rural and semiurban communities of southwestern Nigeria.
      METHODOLOGY: The study was carried out in Ado-Odo/Ota Local Government Area of
      Ogun State. A multistage sampling technique and an informant survey approach were
      used in the study. A total sample of 360 eligible respondents were selected
      randomly from 11 out of 16 political wards in the study area and interviewed
      through the administration of questionnaires. The data were processed using
      descriptive statistics and regression analyses. RESULTS: Place of consultation
      (P=0.000), who pays the treatment costs (P=0.000), awareness of pregnancy
      complications (P=0.002) and knowledge of the place of antenatal care treatment
      (P=0.000) significantly influenced maternal mortality (proxy by place of delivery
      of last birth). The F-statistic (15.100) confirmed the hypothesis that nonmedical
      factors influence maternal mortality. The correlation of predictor variables was
      significant at both the 0.01 level and the 0.05 level (2-tailed). CONCLUSION: Our
      findings suggest that in a rural community setting with a depleted health care
      system, health education tailored toward community culture, subsidized maternal
      health care services by the government and operators of private clinics, as well
      as empowering and improving the status of women may reduce maternal mortality and
      prompt better utilization and survival chances of women in the study area as well
      as in all of Nigeria.

PMID- 28442937
TI  - Simultaneous administration of fluoxetine and simvastatin ameliorates lipid
      profile, improves brain level of neurotransmitters, and increases bioavailability
      of simvastatin.
AB  - Simvastatin (STT), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,
      is widely prescribed for dyslipidemia, whereas fluoxetine (FLX) is the first
      choice drug for the treatment of depression and anxiety. A recent report suggests
      that selective serotonin reuptake inhibitors can interact with the cytochrome
      P450 3A4 substrate, and another one suggests that STT enhances the antidepressant
      activity of FLX. However, the data are inconclusive. The present study was
      designed to explore the pharmacokinetic and pharmacodynamic consequences of
      coadministration of STT and FLX in experimental animals. For this, Wistar rats
      weighing 250+/-10 g were divided into four groups, including control, STT (40
      mg/kg/day), FLX (20 mg/kg/day), and STT+FLX group, respectively. After the dosing
      period of 4 weeks, the animals were sacrificed, and the blood and brain samples
      were collected for the analysis of STT, simvastatin acid (STA), FLX, total
      cholesterol, triglyceride, high-density lipoprotein (HDL), 5-hydroxytryptamine,
      dopamine, and hydroxy indole acetic acid. It was found that the coadministration
      resulted in a significant increase in the bioavailability of STT in the plasma
      (41.8%) and brain (68.7%) compared to administration of STT alone (p<0.05). The
      maximum drug concentration (Cmax) of STT was also found to be increased
      significantly in the plasma and brain compared to that achieved after monotherapy
      (p<0.05). However, STT failed to improve the pharmacokinetics of FLX up to a
      significant level. The results of this study showed that the combined regimen
      significantly reduced the level of cholesterol and triglyceride and increased the
      level of HDL when compared to STT monotherapy. Furthermore, the coadministration
      of STT with FLX led to an elevated level of neurotransmitters in the brain
      (p<0.05). FLX increased the concentration of STT in the plasma and brain. The
      coadministration of these drugs also led to an improved lipid profile. However,
      in the long-term, this interaction may have a vital clinical importance because
      the increase in STT level may lead to life-threatening side effects associated
      with statins.

PMID- 28442938
TI  - Environmental arsenic exposure and risk of diabetes type 2 in Ron Phibun
      subdistrict, Nakhon Si Thammarat Province, Thailand: unmatched and matched case
      control studies.
AB  - BACKGROUND: There are inconsistent findings on associations between low-to
      moderate level of arsenic in water and diabetes risk from previous
      epidemiological reports. In Ron Phibun subdistrict, Nakhon Si Thammarat Province,
      Thailand, a low level of arsenic exposure among population was observed and
      increased diabetes mellitus (DM) rate was identified. OBJECTIVES: We aimed to
      investigate the association between determinants (including low-level water
      arsenic exposure) of DM type 2 risk among residents of three villages of Ron
      Phibun subdistrict, Nakhon Si Thammarat Province. MATERIALS AND METHODS:
      Secondary data from two previous community based-studies, conducted in 2000 and
      2008, were utilized. Data on independent variables relating to arsenic exposure
      and sociodemographic characteristics were taken from questionnaires and
      worksheets for health-risk screening. Water samples collected during household
      visit were sent for analysis of arsenic level at certified laboratories. Diabetes
      cases (N=185) were those who had been diagnosed with DM type 2. Two groups of
      controls, one unmatched to cases (n=200) and one pair matched on age and gender
      (n=200), were selected for analysis as unmatched and matched case-control
      studies, respectively. A multiple imputation technique was used to impute missing
      values of independent variables. Multivariable logistic regression models, with
      independent variables for arsenic exposure and sociodemographic characteristics,
      were constructed. The unmatched and matched data sets were analyzed using
      unconditional and conditional logistic analyses, respectively. RESULTS: Older
      age, body mass index (BMI), having a history of illness in siblings and parents,
      and drinking were associated with increased DM type 2 risk. We found no
      convincing association between DM type 2 risk and water arsenic concentration in
      either study. CONCLUSION: We did not observe meaningful association between
      diabetes risk and the low-to-moderate arsenic levels observed in this study.
      Further research is needed to confirm this finding in the study area and
      elsewhere in Thailand.

PMID- 28442939
TI  - Sleep disturbance linked to suicidal ideation in postural orthostatic tachycardia
      syndrome.
AB  - OBJECTIVE: We investigated the prevalence of suicidal ideation in relationship
      with symptoms of sleep disruption in people with postural orthostatic tachycardia
      syndrome (POTS). METHODS: Online surveys (including the Pittsburgh Sleep Quality
      Index and the Suicide Behaviors Questionnaire - Revised) were completed by 705
      POTS patients and 170 non-POTS controls. RESULTS: Poor sleep quality was reported
      in 98.4% of POTS patients with a calculated subjective sleep efficiency of 65.4%.
      The POTS group's sleep efficiency was significantly lower (t[873]= -11.32;
      p<0.001) and sleep disturbances because of pain were significantly higher
      (t[873]=15.36; p<0.001) than controls. Chi-square testing showed a larger
      proportion of individuals at high-risk for suicide among POTS patients than
      controls (c2 [1, n=875]=55.6; p<0.001). Multiple linear regression analysis
      showed that sleep scores (beta=0.23, p<0.001), age (beta=-0.03, p<0.001), and
      illness with POTS (beta=0.68, p=0.05) were significantly associated with suicide
      ideation scores (F[4, 870]=38.34, p<0.001). This model explained 15% of variance
      (R2=0.15) in suicidal ideation scores. CONCLUSION: Patients with POTS may suffer
      from increased sleep disturbance and suicidal ideation compared with the general
      population. Treatment to improve sleep efficiency and sleep quality is an
      important step toward better quality of life for POTS patients.

PMID- 28442940
TI  - Prevalence of anemia and its associated factors among pregnant women receiving
      antenatal care at Aymiba Health Center, northwest Ethiopia.
AB  - INTRODUCTION: Anemia is a global public health problem in both developing and
      developed countries; ~1.62 billion people suffer from anemia, and pregnant women
      are the most susceptible to it. The main aim of the present study was to assess
      the prevalence of anemia and associated risk factors among pregnant women
      receiving antenatal care at Aymiba Health Center, northwest Ethiopia. METHODS AND
      MATERIALS: An institution-based cross-sectional study was conducted at Aymiba
      Health Center from January to March 2015. Hemoglobin level and intestinal
      parasitic infections in pregnant women were assessed. Sociodemographic data were
      collected using a structured questionnaire. The data were entered and analyzed
      using the SPSS version 20. Odds ratio, p<0.05, and binary logistic regression
      were used to assess the association of pregnant women's sociodemographic
      characteristics with their hemoglobin levels and the prevalence of anemia.
      RESULTS: The mean with +/-2 standard deviation of hemoglobin value was 12+/-1.3
      (95% confidence interval [CI] =11.9-12.5), and the prevalence of anemia from a
      total of 206 study subjects was 52 (25.2%). Of this anemic group, 50 (24%) were
      in the second and third trimesters. Anemia was significantly associated with
      rural residence and intestinal parasitic infections (adjusted odds ratio [AOR]
      =9.17, 95% CI =2.15-40, p<0.001) and (AOR =55.091, 95% CI =6.88-441.19, p<0.001),
      respectively. CONCLUSION: In the present study, the prevalence of anemia was
      lower than in previous studies conducted in various countries, including
      Ethiopia. More studies are needed regarding the importance of regular maternal
      care and health education promotion programs, which have the potential to play a
      more significant role in health care.

PMID- 28442941
TI  - Competency-based tool for evaluation of community-based training in undergraduate
      medical education in India - a Delphi approach.
AB  - INTRODUCTION: A community-based training (CBT) program, where teaching and
      training are carried out in the community outside of the teaching hospital, is a
      vital part of undergraduate medical education. Worldwide, there is a shift to
      competency-based training, and CBT is no exception. We attempted to develop a
      tool that uses a competency-based approach for assessment of CBT. METHODS: Based
      on a review on competencies, we prepared a preliminary list of major domains with
      items under each domain. We used the Delphi technique to arrive at a consensus on
      this assessment tool. The Delphi panel consisted of eight purposively selected
      experts from the field of community medicine. The panel rated each item for its
      relevance, sensitivity, specificity, and understandability on a scale of 0-4.
      Median ratings were calculated at the end of each round and shared with the
      panel. Consensus was predefined as when 70% of the experts gave a rating of 3 or
      above for an item under relevance, sensitivity, and specificity. If an item
      failed to achieve consensus after being rated in 2 consecutive rounds, it was
      excluded. Anonymity of responses was maintained. RESULTS: The panel arrived at a
      consensus at the end of 3 rounds. The final version of the self-assessment tool
      consisted of 7 domains and 74 items. The domains (number of items) were Public
      health - epidemiology and research methodology (13), Public health -
      biostatistics (6), Public health administration at primary health center level
      (17), Family medicine (24), Cultural competencies (3), Community development and
      advocacy (2), and Generic competence (9). Each item was given a maximum score of
      5 and minimum score of 1. CONCLUSION: This is the first study worldwide to
      develop a tool for competency-based evaluation of CBT in undergraduate medical
      education. The competencies identified in the 74-item questionnaire may provide
      the base for development of authentic curricula for CBT.

PMID- 28442942
TI  - Comparison in the quality of distractors in three and four options type of
      multiple choice questions.
AB  - INTRODUCTION: The number of distractors needed for high quality multiple choice
      questions (MCQs) will be determined by many factors. These include firstly
      whether English language is their mother tongue or a foreign language; secondly
      whether the instructors who construct the questions are experts or not; thirdly
      the time spent on constructing the options is also an important factor. It has
      been observed by Tarrant et al that more time is often spent on constructing
      questions than on tailoring sound, reliable, and valid distractors. OBJECTIVES:
      Firstly, to investigate the effects of reducing the number of options on
      psychometric properties of the item. Secondly, to determine the frequency of
      functioning distractors among three or four options in the MCQs examination of
      the dermatology course in University of Bahri, College of Medicine. MATERIALS AND
      METHODS: This is an experimental study which was performed by means of a
      dermatology exam, MCQs type. Forty MCQs, with one correct answer for each
      question were constructed. Two sets of this exam paper were prepared: in the
      first one, four options were given, including one key answer and three
      distractors. In the second set, one of the three distractors was deleted
      randomly, and the sequence of the questions was kept in the same order. Any
      distracter chosen by less than 5% of the students was regarded as non
      functioning. Kuder-Richardson Formula 20 (Kr-20) measures the internal
      consistency and reliability of an examination with an acceptable range 0.8-1.0.
      Chi square test was used to compare the distractors in the two exams. RESULTS: A
      significant difference was observed in discrimination and difficulty indexes for
      both sets of MCQs. More distractors were non-functional for set one (of four
      options), but slightly more reliable. The reliability (Kr-20) was slightly higher
      for set one (of four options). The average marks in option three and four were
      34.163 and 33.140, respectively. CONCLUSION: Compared to set 1 (four options),
      set 2 (of three options) was more discriminating and associated with low
      difficulty index but its reliability was low.

PMID- 28442943
TI  - Flow Shear Stress Enhances the Proliferative Potential of Cultured Radial Glial
      Cells Possibly Via an Activation of Mechanosensitive Calcium Channel.
AB  - Radial glial cells (RGCs) which function as neural stem cells are known to be non
      excitable and their proliferation depends on the intracellular calcium (Ca2+)
      level. It has been well established that Inositol 1,4,5-trisphosphate (IP3)
      mediated Ca2+ release and Ca2+ entry through various Ca2+ channels are involved
      in the proliferation of RGCs. Furthermore, RGCs line the ventricular wall and are
      exposed to a shear stress due to a physical contact with the cerebrospinal fluid
      (CSF). However, little is known about how the Ca2+ entry through mechanosensitive
      ion channels affects the proliferation of RGCs. Hence, we hypothesized that shear
      stress due to a flow of CSF boosts the proliferative potential of RGCs possibly
      via an activation of mechanosensitive Ca2+ channel during the embryonic brain
      development. Here, we developed a new microfluidic two-dimensional culture system
      to establish a link between the flow shear stress and the proliferative activity
      of cultured RGCs. Using this microfluidic device, we successfully visualized the
      artificial CSF and RGCs in direct contact and found a significant enhancement of
      proliferative capacity of RGCs in response to increased shear stress. To
      determine if there are any mechanosensitive ion channels involved, a mechanical
      stimulation by poking was given to individual RGCs. We found that a poking on
      radial glial cell induced an increase in intracellular Ca2+ level, which
      disappeared under the extracellular Ca2+-free condition. Our results suggest that
      the shear stress by CSF flow possibly activates mechanosensitive Ca2+ channels,
      which gives rise to a Ca2+ entry which enhances the proliferative capacity of
      RGCs.

PMID- 28442944
TI  - Immunohistochemical Localization of Translationally Controlled Tumor Protein in
      Axon Terminals of Mouse Hippocampal Neurons.
AB  - Translationally controlled tumor protein (TCTP) is a cytosolic protein with
      microtubule stabilization and calcium-binding activities. TCTP is expressed in
      most organs including the nervous system. However, detailed distribution and
      functional significance of TCTP in the brain remain unexplored. In this study, we
      investigated the global and subcellular distributions of TCTP in the mouse brain.
      Immunohistochemical analyses with anti-TCTP revealed that TCTP was widely
      distributed in almost all regions of the brain including the cerebral cortex,
      thalamus, hypothalamus, hippocampus, and amygdala, wherein it was localized in
      axon tracts and axon terminals. In the hippocampus, TCTP was prominently
      localized to axon terminals of the perforant path in the dentate gyrus, the mossy
      fibers in the cornu ammonis (CA)3 region, and the Schaffer collaterals in the CA1
      field, but not in cell bodies of granule cells and pyramidal neurons, and in
      their dendritic processes. Widespread distribution of TCTP in axon tracts and
      axon terminals throughout the brain suggests that TCTP is likely involved in
      neurotransmitter release and/or maintaining synaptic structures in the brain, and
      that it might have a role in maintaining synaptic functions and synaptic
      configurations important for normal cognitive, stress and emotional functions.

PMID- 28442945
TI  - Pulse-train Stimulation of Primary Somatosensory Cortex Blocks Pain Perception in
      Tail Clip Test.
AB  - Human studies of brain stimulation have demonstrated modulatory effects on the
      perception of pain. However, whether the primary somatosensory cortical activity
      is associated with antinociceptive responses remains unknown. Therefore, we
      examined the antinociceptive effects of neuronal activity evoked by optogenetic
      stimulation of primary somatosensory cortex. Optogenetic transgenic mice were
      subjected to continuous or pulse-train optogenetic stimulation of the primary
      somatosensory cortex at frequencies of 15, 30, and 40 Hz, during a tail clip
      test. Reaction time was measured using a digital high-speed video camera. Pulse
      train optogenetic stimulation of primary somatosensory cortex showed a delayed
      pain response with respect to a tail clip, whereas no significant change in
      reaction time was observed with continuous stimulation. In response to the pulse
      train stimulation, video monitoring and local field potential recording revealed
      associated paw movement and sensorimotor rhythms, respectively. Our results show
      that optogenetic stimulation of primary somatosensory cortex at beta and gamma
      frequencies blocks transmission of pain signals in tail clip test.

PMID- 28442946
TI  - Optogenetic Rescue of Locomotor Dysfunction and Dopaminergic Degeneration Caused
      by Alpha-Synuclein and EKO Genes.
AB  - alpha-Synuclein (alpha-Syn) is a small presynaptic protein and its mutant forms
      (e.g. A53T) are known to be directly associated with Parkinson's disease (PD).
      Pathophysiological mechanisms underlying alpha-Syn-mediated neurodegeneration in
      PD still remain to be explored. However, several studies strongly support that
      overexpression of mutant alpha-Syn causes reduced release of dopamine (DA) in the
      brain, and contributes to motor deficits in PD. Using a favorable genetic model
      Drosophila larva, we examined whether reduced DA release is enough to induce key
      PD symptoms (i.e. locomotion deficiency and DA neurodegeneration), mimicking a PD
      gene alpha-Syn. In order to reduce DA release, we expressed electrical knockout
      (EKO) gene in DA neurons, which is known to make neurons hypo-excitable. EKO led
      to a decrease in a DA neuronal marker signal (i.e., TH - tyrosine hydroxylase)
      and locomotion deficits in Drosophila larva. In contrast, acute and prolonged
      exposure to blue light (BL, 470 nm) was sufficient to activate channelrhodopsin 2
      (ChR2) and rescue PD symptoms caused by both alpha-Syn and EKO. We believe this
      is for the first time to confirm that locomotion defects by a genetic PD factor
      such as alpha-Syn can be rescued by increasing DA neuronal excitability with an
      optogenetic approach. Our findings strongly support that PD is a failure of DA
      synaptic transmission, which can be rescued by optogenetic activation of ChR2.

PMID- 28442949
TI  - Combined preincisional periportal and preperitoneal infiltration with bupivacaine
      in pain relief after laparoscopic surgery.

PMID- 28442947
TI  - A High-fat Diet Induces a Loss of Midbrain Dopaminergic Neuronal Function That
      Underlies Motor Abnormalities.
AB  - Movement defects in obesity are associated with peripheral muscle defects,
      arthritis, and dysfunction of motor control by the brain. Although movement
      functionality is negatively correlated with obesity, the brain regions and
      downstream signaling pathways associated with movement defects in obesity are
      unclear. A dopaminergic neuronal pathway from the substantia nigra (SN) to the
      striatum is responsible for regulating grip strength and motor initiation through
      tyrosine hydroxylase (TH) activity-dependent dopamine release. We found that mice
      fed a high-fat diet exhibited decreased movement in open-field tests and an
      increase in missteps in a vertical grid test compared with normally fed mice.
      This motor abnormality was associated with a significant reduction of TH in the
      SN and striatum. We further found that phosphorylation of c-Jun N-terminal kinase
      (JNK), which modulates TH expression in the SN and striatum, was decreased under
      excess-energy conditions. Our findings suggest that high calorie intake impairs
      motor function through JNK-dependent dysregulation of TH in the SN and striatum.

PMID- 28442950
TI  - Effect of intranasal dexmedetomidine on emergence agitation after sevoflurane
      anesthesia in children undergoing tonsillectomy and/or adenoidectomy.
AB  - BACKGROUND: Emergence agitation (EA) after sevoflurane anesthesia is common in
      children during recovery from general anesthesia and may result in postoperative
      complications. This study investigated safety and effectiveness of intranasal
      dexmedetomidine in reducing the incidence and severity of EA. METHODS: This
      prospective, randomized double-blinded controlled trial included 86 patients
      scheduled for the tonsillectomy and/or adenoidectomy under general anesthesia
      with sevoflurane. They were randomly allocated into two groups. Group D received
      intranasal dexmedetomidine at 1 MUg/kg, and Group C received intranasal saline
      0.9% after the induction of general anesthesia. Four-point agitation scale and
      Face, Legs, Activity, Cry and Consolability (FLACC) scale for pain assessment
      were measured at six time points (after extubation, leaving the operating room,
      on arrival to postanesthesia care unit [PACU], 10, 20, and 30 min after arrival
      in PACU). Extubation, emergence, and discharge times were recorded in addition to
      any adverse effects. RESULTS: There was a significant difference in the incidence
      of EA between Groups D and C (6.98% and 58%, respectively, with P = 0.001). The
      median four-point agitation scales and the median scores of FLACC pain scales of
      Group D were significantly lower than those of Group C at the all six time points
      with P < 0.05. Extubation, emergence, and discharge times were comparable in both
      groups, and none of the subjects reported any adverse effects. CONCLUSION: This
      study demonstrates that a 1 MUg/kg dose of intranasal dexmedetomidine
      administered after the induction of anesthesia reduces post-sevoflurane incidence
      and severity of EA in children undergone tonsillectomy and/or adenoidectomy with
      no adverse effects and smooth recovery profile.

PMID- 28442951
TI  - Renal water conservation determines the increase in body weight after surgery: A
      randomized, controlled trial.
AB  - BACKGROUND: The present study was undertaken to identify factors that correlate
      with the gain in body weight after surgery. METHODS: Twenty-one patients (median
      age of 49 years) were randomized to receive either Ringer * s acetate or 6%
      dextran 70 as their first infusion fluid during cholecystectomy or hysterectomy.
      Each patient's body weight was measured before the surgery and on the first
      postoperative morning. Blood and urine samples were analyzed for signs of stress,
      inflammation, and kidney injury. The fluid retention index (FRI), which reflects
      how strongly the kidneys excrete or retain fluid, was also calculated. RESULTS:
      The body weight increased by a median of 0.4 kg in the crystalloid fluid group
      and by 1.0 kg in the colloid fluid group (maximum 2.5 kg, P < 0.01). This
      difference was due to less urinary excretion after surgery in the colloid group
      (P < 0.03). The increase in body weight did not correlate with the infused fluid
      volume, the plasma concentrations of C-reactive protein or cortisol, or the
      urinary excretion of albumin, cortisol, or neutrophil gelatinase-associated
      lipocalin. However, the body weight increased with the postoperative FRI score (r
      = 0.64; P < 0.003) and with the surgery-induced change in FRI score (r = 0.72; P
      < 0.002). CONCLUSION: How strongly the kidneys excrete or retain fluid, which can
      be assessed by urine sampling, was the strongest indicator of the increase in
      body weight during the day of surgery. The amount of fluid alone did not
      correlate with the gain in body weight.

PMID- 28442952
TI  - Comparison of onset anesthesia time and injection discomfort of 4% articaine and
      2% mepivacaine during teeth extractions.
AB  - OBJECTIVE: To investigate the speed of action and injection discomfort of 4%
      articaine and 2% mepivacaine for upper teeth extractions. MATERIALS AND METHODS:
      Forty-five patients were included in the articaine 4% group, and 45 in the
      mepivacaine 2% control group. After all injections, soft and hard tissue numbness
      was objectively gauged by dental probe at intervals of 15 s. Furthermore, the
      discomfort of the injections were recorded by the patients after each treatment
      on standard 100 mm visual analog scales, tagged at the endpoints with "no pain"
      (0 mm) and "unbearable pain" (100 mm). RESULTS: There were significant
      differences in the meantime of first numbness to associated palatal mucosa and
      tooth of patients between mepivacaine and articaine buccal infiltration (BI)
      groups P = 0.01 and 0.01. Patients in the articaine group recorded earlier
      palatal mucosa and teeth numbness than those in the mepivacaine group. With
      regards to the discomfort of the needle injections, palatal injection was
      significantly more painful than BI (t-test: P < 0.001). Articaine buccal
      injection was significantly more painful than mepivacaine buccal injection (t
      test: P <0.001). However, articaine palatal injection was less painful than
      articaine BI. Clinically, anesthesia onset time was faster in anterior upper
      teeth than upper middle and posterior teeth. CONCLUSIONS: BIs with 4% articaine
      was faster in achieving palate and teeth anesthesia than 2% mepivacaine for
      extraction of upper maxillary teeth. Patients in mepivacaine BI and articaine
      palatal injection groups reported less pain with needle injection. Failure of
      anesthesia was noticeable with maxillary multiple-rooted teeth.

PMID- 28442953
TI  - Role of flupirtine in reducing preoperative anxiety of patients undergoing
      craniotomy procedure.
AB  - BACKGROUND: Kv7 neuronal channels are recognized as a potential drug target for
      anxiolytic effects. We hypothesize that flupirtine as a potassium channel opener
      would effectively reduce the preoperative anxiety of patients undergoing
      craniotomy procedure. METHODS: In prospective-double-blinded fashion, 124
      counseled patients were randomized to receive 5 sequential doses of capsule
      flupirtine 100 mg (F Group) or physically similar starch capsules (C Group), at
      12 h intervals during preoperative hospitalization. Primary outcome included
      various aspects of patient anxiety measured by visual analog scale (VAS) just
      before preoperative counseling and 2 h after the completion of drug regimen under
      trial. Statistical tool included Mann-Whitney U-test and Wilcoxon signed rank
      test. RESULTS: Baseline VAS scores were higher for fear of surgical harm, being
      at the mercy of medical staff, and not awakening after surgery. A significant
      decline in VAS scores was observed after the completion of drug regime, but to a
      higher extent in flupirtine-treated patients; it achieved statistical
      significance in comparison to Group C. No side effects were observed in any
      patient. CONCLUSION: Flupirtine is a useful premedication in conjunction with
      behavioral therapy to alleviate patient anxiety during the preoperative period.

PMID- 28442954
TI  - Evaluation of efficacy of dexmedetomidine versus propofol for sedation in
      children undergoing magnetic resonance imaging.
AB  - BACKGROUND: A deep level of sedation is required for magnetic resonance imaging
      (MRI) in children to ensure optimum image quality. The present study was
      conducted to evaluate the efficacy and safety of dexmedetomidine versus propofol
      for sedation in children undergoing MRI. MATERIALS AND METHODS: A total of sixty
      children aged 2-10 years, having physical status 1 or 2 according to the American
      Society of Anesthesiologists, undergoing MRI were included in the study. Group D:
      (n = 30) received injection dexmedetomidine 2 MUg/kg for 10 min followed by
      continuous infusion of 1.0 MUg/kg/h. Group P (n = 30) received injection propofol
      1 mg/kg bolus followed by continuous infusion of 100 MUg/kg/min. RESULTS: The
      mean time for onset of sedation in Group D was much longer than in Group P (P =
      0.000). Mean duration of sedation was comparable in the two groups. The number of
      patients requiring increased infusion of study drug was significantly higher in
      Group D (30%) as compared to Group P (16.7%) (P < 0.05). The average recovery
      time in Group D was much longer than in Group P (P < 0.001). CONCLUSION: Propofol
      had an advantage of providing rapid onset of sedation and quicker recovery time.
      Dexmedetomidine resulted in a better preservation of respiratory rate and oxygen
      saturation, so it may be more suitable in children who are prone to respiratory
      depression. Hence, both the drugs could achieve required sedation in children
      posted for MRI.

PMID- 28442955
TI  - No preemptive analgesic effect of preoperative ketorolac administration following
      total abdominal hysterectomy: A randomized study.
AB  - BACKGROUND: Experimental models using short-duration noxious stimuli have led to
      the concept of preemptive analgesia. Ketorolac, a nonsteroidal anti-inflammatory
      drug, has been shown to have a postoperative narcotic-sparing effect when given
      preoperatively and alternatively to not have this effect. This study was
      undertaken to determine whether a single intravenous (IV) dose of ketorolac would
      result in decreased postoperative pain and narcotic requirements. METHODS: In a
      double-blind, randomized controlled trial, 48 women undergoing abdominal
      hysterectomy were studied. Patients in the ketorolac group received 30 mg of IV
      ketorolac 30 min before surgical incision, while the control group received
      normal saline. The postoperative analgesia was performed with a continuous
      infusion of tramadol at 12 mg/h with the possibility of a 10 mg bolus for every
      10 min. Pain was assessed using the visual analog scale (VAS), tramadol
      consumption, and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16, and 24 h
      postoperatively. We quantified times to rescue analgesic (morphine), adverse
      effects, and patient satisfaction. RESULTS: There were neither significant
      differences in VAS scores between groups (P > 0.05) nor in the cumulative or
      incremental consumption of tramadol at any time point (P > 0.05). The time to
      first requested rescue analgesia was 66.25 +/- 38.61 min in the ketorolac group
      and 65 +/- 28.86 min in the control group (P = 0.765). There were no significant
      differences in systolic blood pressure (BP) between both groups, except at 2 h (P
      = 0.02) and 4 h (P = 0.045). There were no significant differences in diastolic
      BP between both groups, except at 4 h (P = 0.013). The respiratory rate showed no
      differences between groups, except at 8 h (P = 0.017), 16 h (P = 0.011), and 24 h
      (P = 0.049). These differences were not clinically significant. There were no
      statistically significant differences between groups in heart rate (P > 0.05).
      CONCLUSIONS: Preoperative ketorolac neither showed a preemptive analgesic effect
      nor was it effective as an adjuvant for decreasing opioid requirements or
      postoperative pain in patients receiving IV analgesia with tramadol after
      abdominal hysterectomy.

PMID- 28442956
TI  - A comparison between intravenous lidocaine and ketamine on acute and chronic pain
      after open nephrectomy: A prospective, double-blind, randomized, placebo
      controlled study.
AB  - BACKGROUND: Recently, there has been increasing interest in the use of analgesic
      adjuncts such as intravenous (IV) ketamine and lidocaine. OBJECTIVES: To compare
      the effects of perioperative IV lidocaine and ketamine on morphine requirements,
      pain scores, quality of recovery, and chronic pain after open nephrectomy. STUDY
      DESIGN: A prospective, randomized, placebo-controlled, double-blind trial.
      SETTINGS: The study was conducted in Charles Nicolle University Hospital of
      Tunis. METHODS: Sixty patients were randomly allocated to receive IV lidocaine:
      bolus of 1.5 mg/kg at the induction of anesthesia followed by infusion of 1
      mg/kg/h intraoperatively and for 24 h postoperatively or ketamine: bolus of 0.15
      mg/kg followed by infusion of 0.1 mg/kg/h intraoperatively and for 24 h
      postoperatively or an equal volume of saline (control group [CG]). MEASUREMENTS:
      Morphine consumption, visual analog scale pain scores, time to the first passage
      of flatus and feces, postoperative nausea and vomiting (PONV), 6-min walk
      distance (6MWD) at discharge, and the incidence of chronic neuropathic pain using
      the "Neuropathic Pain Questionnaire" at 3 months. RESULTS: Ketamine and lidocaine
      reduced significantly morphine consumption (by about 33% and 42%, respectively)
      and pain scores compared with the CG (P < 0.001). Lidocaine and ketamine also
      significantly improved bowel function in comparison to the CG (P < 0.001).
      Ketamine failed to reduce the incidence of PONV. The 6 MWD increased
      significantly from a mean +/- standard deviation of 27 +/- 16.2 m in the CG to
      82.3 +/- 28 m in the lidocaine group (P < 0.001). Lidocaine, but not ketamine,
      reduced significantly the development of neuropathic pain at 3 months (P < 0.05).
      CONCLUSION: Ketamine and lidocaine are safe and effective adjuvants to decrease
      opioid consumption and control early pain. We also suggest that lidocaine
      infusion serves as an interesting alternative to improve the functional walking
      capacity and prevent chronic neuropathic pain at 3 months after open nephrectomy.

PMID- 28442957
TI  - Efficacy and safety of intravenous thiopental for sedation during magnetic
      resonance imaging in pediatric patients: A retrospective analysis.
AB  - INTRODUCTION: Although the administration of rectal thiopental for sedation
      during magnetic resonance imaging (MRI) has been well described, there are
      limited data regarding its intravenous (IV) use in this clinical scenario. The
      aim of this study was to investigate the efficiency of IV thiopental for sedation
      during MRI in the pediatric population. METHODS: A retrospective review was
      conducted over a 12-month period of pediatric patients who received IV thiopental
      for sedation during MRI. Data collected included the procedure length, the
      induction dose, the time to sedation, recovery time, total sedation time, and
      adverse events. The parents were telephoned and questioned regarding any adverse
      effect after discharge and their satisfaction (yes = satisfied; no = not
      satisfied) regarding the sedation process. RESULTS: A total of 300 (American
      Society of Anesthesiology I-II status) pediatric patients received IV thiopental
      for sedation during MRI. The average age of the patients was 4.7 +/- 3 years.
      Thiopental was administered as an initial IV bolus dose of 3 mg/kg, followed by
      additional bolus doses of thiopental (1 mg/kg) as needed to achieve a Ramsay
      sedation score of 4. The average procedure length was 20.7 +/- 11.9 min. The
      average total dose of thiopental during the procedure was 5.6 +/- 0.9 mg/kg.
      Patients recovered in an average time of 11 +/- 5.6 min after a total sedation
      time of 31.7 +/- 14.2 min. None of the patients had oxygen desaturation, adverse
      effects before or after discharge, and no patient required unplanned hospital
      admission. All parents were satisfied with the sedation process. CONCLUSION: IV
      thiopental is an effective, safe, and inexpensive medication for the sedation of
      children undergoing MRI.

PMID- 28442958
TI  - Physiological and operative severity score for the enumeration of mortality and
      morbidity scoring systems for assessment of patient outcome and impact of
      surgeons' and anesthesiologists' performance in hepatopancreaticobiliary surgery.
AB  - CONTEXT: The physiological and operative severity score for the enumeration of
      mortality and morbidity (POSSUM) is a scoring system used to predict morbidity
      and mortality. AIMS: We compared the physiological and operative risk, the
      expected morbidity and mortality, and the observed postoperative mortality among
      patients operated by different surgeons and anesthetized by different
      anesthesiologists. SETTINGS AND DESIGN: This was a retrospective, single center
      study. SUBJECTS AND METHODS: The anesthetic records of 159 patients who underwent
      hepatopancreaticobiliary surgery were analyzed for the physiological and
      operative severity, POSSUM morbidity, POSSUM and Portsmouth POSSUM (P-POSSUM)
      mortality scoring systems, observed mortality in 30-days, 3, 6, and 12 months
      postoperatively, duration of surgery, and units of packed red blood cells (PRBC)
      transfused. These variables were compared among patients operated by five
      different surgeons and anesthetized by seven different anesthesiologists.
      STATISTICAL ANALYSIS: One-way analysis of variance was used for normally and
      Kruskal-Wallis test for nonnormally distributed responses. Differences in
      percentages of postoperative mortality were assessed by Chi-squared test.
      RESULTS: The physiological severity, POSSUM morbidity, POSSUM and P-POSSUM
      mortality scores, and observed mortality at 1, 3, 6, and 12 months
      postoperatively did not differ among patients operated by different surgeons and
      anesthetized by different anesthesiologists. Duration of surgery (P < 0.001),
      PRBC units transfused (P = 0.002), and operative severity (P = 0.001) differed
      significantly among patients operated by different surgeons. CONCLUSIONS: The
      physiological severity score, POSSUM and P-POSSUM scores did not differ among
      patients operated by different surgeons and anesthetized by different
      anesthesiologists. The different operative severity scores did not influence the
      observed mortality in the postoperative period.

PMID- 28442959
TI  - Evaluation of different doses of dexmedetomidine alone versus the combination of
      dexmedetomidine and fentanyl in sedation during awake fiberoptic intubation in
      oral cancer surgery patients: A prospective, randomized, double-blind clinical
      trial.
AB  - BACKGROUND: Awake fiberoptic intubation (AFOI) is one of the principal techniques
      in the management of difficult airway in oral cancer surgery. We hypothesized
      that the addition of a small dose of fentanyl could improve the sedative criteria
      of dexmedetomidine during AFOI technique, without the need to increase the dose
      of dexmedetomidine which may be associated with airway compromise. PATIENTS AND
      METHODS: One hundred and fifty American Society of Anesthesiologists physical
      status 1 and 2 patients planned for AFOI for oral cancer surgery patients were
      allocated into three groups (fifty patients each). Group D1: Received an infusion
      of 1 MUcg/kg dexmedetomidine diluted in 50 ml saline over 20 min. Group D2:
      Received an infusion of 2 MUcg/kg dexmedetomidine diluted in 50 ml saline over 20
      min. Group DF: Received an infusion of 1 MUcg/kg dexmedetomidine added to 1
      MUcg/kg fentanyl diluted in 50 ml saline over 20 min. AFOI was done by topical
      anesthesia and with the same technique in all patients. All patients were
      assessed for: airway obstruction, intubation scores (vocal cord movement,
      coughing, and limb movement), fiberoptic intubation scores, and hemodynamic
      variables. Any episode of bradycardia or hypoxia was recorded and managed.
      RESULTS: Group D2 showed more incidence of airway obstruction than the other two
      groups. Limb movement scores were more in Group D1 compared to the other two
      groups. All groups were comparable as regard fiberoptic intubation scores,
      coughing, and vocal cord opening scores. CONCLUSION: Adding a low dose of
      fentanyl (1 MUcg/kg) to a low dose of dexmedetomidine can prevent the risk of
      airway obstruction associated with increasing the dose of dexmedetomidine while
      achieving the same favorable intubation scores.

PMID- 28442960
TI  - Cricoid ring: Shape, size, and variability in infants and children.
AB  - BACKGROUND: Knowledge regarding the shape, size, and variability of the cricoid
      ring is important to properly choose the correct endotracheal tube (ETT) in the
      pediatric patient. Studies have measured the size of the cricoid ring using
      methodologies such as moulages, magnetic resonance imaging, and video
      bronchoscopy. In the present study, computed tomography (CT) -based images were
      used to determine the shape, size, and configuration of the cricoid ring in the
      pediatric population taking into considerations growth and development. METHODS:
      This is a retrospective review using 130 CT images of children ranging in age
      from 1 month to 10 years undergoing radiological evaluation unrelated to airway
      symptomatology. The CT scans were obtained in spontaneously breathing patients
      during either natural sleep or procedural sedation. Anteroposterior (AP) and
      transverse (T) diameters were measured at the cricoid ring using these images.
      RESULTS: The cricoid ring is generally round in children older than 1 year with a
      T/AP ratio ranging between 0.98 and 1.01. However, in infants (1-12 months of
      age), the cricoid ring is elliptical with the AP dimension an average of 0.31 mm
      larger than the T dimension with a T/AP ratio of 0.95. A statistically
      significant difference between the T and AP dimensions was only observed in
      infancy (P < 0.05). CONCLUSION: The cricoid ring is round in children older than
      1 year of age. In infants, the cricoid shape presents a more elliptical
      configuration because the T-axis is narrower than the AP dimension. CT is
      recognized as the most accurate technique to study cricoid ring configuration,
      and the present data may help clinicians determine the appropriate type, size,
      and shape of ETTs, particularly in infants.

PMID- 28442961
TI  - Integration of simulation in postgraduate studies in Saudi Arabia: The current
      practice in anesthesia training program.
AB  - The educational programs in the Saudi Commission for Health Specialties are
      developing rapidly in the fields of technical development. Such development is
      witnessed, particularly in the scientific areas related to what is commonly known
      as evidence-based medicine. This review highlights the critical need and
      importance of integrating simulation into anesthesia training and assessment.
      Furthermore, it describes the current utilization of simulation in anesthesia and
      critical care assessment process.

PMID- 28442962
TI  - Migrated esophageal stent posing a challenge for ventilation.
AB  - Self-expandable esophageal stents are being commonly used for palliative
      treatment in advanced esophageal cancer patients to relieve dysphagia, prevent
      tracheoesophageal fistula, and facilitate symptomatic betterment. The modern
      covered stents reduce the ingrowth of the tumor but have seen an increase in the
      incidence of stent migrations. We report a rather complicated presentation of an
      esophageal stent for esophageal dilatation and a challenging management of a
      difficult tracheostomy.

PMID- 28442963
TI  - Sugammadex to reverse neuromuscular blockade and provide optimal conditions for
      motor-evoked potential monitoring.
AB  - Sugammadex is a novel pharmacologic agent, which reverses neuromuscular blockade
      (NMB) via a mechanism that differs completely from acetylcholinesterase
      inhibitors. By encapsulating rocuronium, sugammadex can provide recovery of
      neuromuscular function even when there is a profound degree of NMB. We report
      anecdotal experience with the use of sugammadex to reverse NMB to facilitate
      intraoperative neurophysiological monitoring (motor evoked potentials) in an
      adolescent with scoliosis during posterior spinal fusion. Its potential
      application in this unique clinical scenario is discussed, and potential dosing
      schemes are reviewed.

PMID- 28442964
TI  - "Graded" epidural anesthesia for renal transplant in a patient with dilated
      cardiomyopathy and severe left ventricle systolic dysfunction.
AB  - Dilated cardiomyopathy with decreased contractility of left or both ventricles
      impose a serious risk to patient posted for major surgery. Even after best
      medical optimization, careful perioperative management with risk and benefit of
      general and regional anesthesia should be discussed beforehand. We here reporting
      a case of successful management of a patient with dilated cardiomyopathy with
      ejection fraction of 15% posted for renal transplant surgery under graded
      epidural anesthesia.

PMID- 28442965
TI  - Unusual airways management during one-lung ventilation in thoracic surgery.
AB  - Airways management in thoracic surgery is usually more difficult than in other
      surgery. We reported a case of a patient who underwent surgery of evacuation of
      empyema where after a correct insertion of a left double-lumen tube 37 Fr (DLT),
      one-lung ventilation was not permitted by the high airways pressure. In fact, the
      hole of bronchial tip was just against the left bronchial wall retracted probably
      from inflammatory process. We introduced blindly an Arndt blocker 9 Fr inside the
      tracheal lumen of DLT until the orifice of the right upper lobe bronchus, the
      distance was checked before. After the positioning of the blocker, the DLT was
      pulled up to above the carina, and the single-lung ventilation was permitted.
      Sometimes, an unusual use of different devices permits to manage complications.
      In fact, in this case, the Arndt bronchial blocker helps us to solve an important
      ventilatory problem.

PMID- 28442966
TI  - Successful management of a broken epidural catheter!!!
AB  - Breakage of epidural catheter though rare is a well-known but worrisome
      complication. Visualization of retained catheter is difficult even with modern
      radiological imaging techniques, and active surgical intervention might be
      necessary for removal of catheter fragment. We report such a case of breakage of
      an epidural catheter during its removal which led to surgical intervention.

PMID- 28442967
TI  - A case report of suspected malignant hyperthermia where patient survived the
      episode.
AB  - Malignant hyperthermia is rare inherited disorder in our part of the world; there
      are only few cases reported in literature in India who were suspected of having
      this condition. The overall incidence of malignant hyperthermia during general
      anesthesia is estimated to range from 1: 5000 to 1: 50,000-100,000 and mortality
      rate is estimated to be <5% in the presence of standard care. In India, there is
      no center where in vitro halothane caffeine contraction test is performed to
      confirm diagnosis in suspected cases. Second, dantrolene drug of choice for this
      condition is not freely available in market in India and is stored only in some
      hospitals in few major cities. Among the cases reported of suspected of malignant
      hyperthermia in India almost 50% have survived the condition despite
      nonavailability of dantrolene emphasizing role of early detection and aggressive
      management in these cases.

PMID- 28442968
TI  - Sonographic detection of tracheal or esophageal intubation: A cadaver study.

PMID- 28442969
TI  - Prevertebral abscess and airway obstruction.

PMID- 28442970
TI  - Incidental detection of spontaneous floating internal jugular vein thrombosis
      with acute pulmonary embolism.

PMID- 28442972
TI  - Screening ultrasound: A valuable tool to detect central venous thrombosis in a
      patient with multiple previous cannulation attempts.

PMID- 28442971
TI  - Stroke complicating penetrating heart injury: Keys to the diagnostic workup and
      management.

PMID- 28442973
TI  - An indigenous in-line metered dose inhaler actuation device.

PMID- 28442974
TI  - Balloon occlusion of internal iliac arteries in placenta accreta!

PMID- 28442975
TI  - Ultrasound-guided trigeminal nerve block for faciomaxillary surgeries.

PMID- 28442976
TI  - Ultrasound-guided thoracolumbar interfascial plane block for spine surgery.

PMID- 28442977
TI  - Perioperative steroid supplementation: Controversies continues!!

PMID- 28442978
TI  - The value of ultrasound sliding sign technique in predicting adhesion-related
      complications: The point of view of the gynecologist and the anesthesiologist.

PMID- 28442979
TI  - "Anesthesia bubbles:" Demystifying the enigma!

PMID- 28442980
TI  - Safety issues of endobronchial intubation for one-lung ventilation in video
      assisted thoracoscopic surgery in neonates: Can we extubate on the table?

PMID- 28442981
TI  - Intracardiac thrombosis after liver transplantation: Can be detected before
      surgery?

PMID- 28442982
TI  - A simple method to reduce pulse oximetry interference by surgical optical
      navigation systems.

PMID- 28442983
TI  - Is dexmedetomidine safe?

PMID- 28442984
TI  - A case of ingested laryngoscope bulb during emergency endotracheal intubation.

PMID- 28442985
TI  - Why should a "gasless" oncologic robotic procedure be performed?

PMID- 28442986
TI  - No-show as a cause of surgical cancellation: A mini review from a Middle Eastern
      perspective.

PMID- 28442987
TI  - Compression at Myofascial Trigger Point on Chronic Neck Pain Provides Pain Relief
      through the Prefrontal Cortex and Autonomic Nervous System: A Pilot Study.
AB  - Compression at myofascial trigger points (MTrPs), known as "ischemic
      compression," has been reported to provide immediate relief of musculoskeletal
      pain and reduce the sympathetic activity that exacerbates chronic pain. We
      conducted a pilot study to investigate the possible involvement of the prefrontal
      cortex in pain relief obtained by MTrP compression in the present study, and
      analyzed the relationships among prefrontal hemodynamic activity, activity of the
      autonomic nervous system, and subjective pain in patients with chronic neck pain,
      with and without MTrP compression. Twenty-one female subjects with chronic neck
      pain were randomly assigned to two groups: MTrP compression (n = 11) or Non-MTrP
      compression (n = 10). Compression for 30 s was conducted 4 times. During the
      experiment, prefrontal hemodynamic activity [changes in Oxy-hemoglobin (Hb),
      Deoxy-Hb, and Total-Hb concentrations] and autonomic activity based on heart rate
      variability (HRV) were monitored by using near infrared spectroscopy (NIRS) and
      electrocardiography (ECG), respectively. The results indicated that MTrP
      compression significantly reduced subjective pain compared with Non-MTrP
      compression. The spectral frequency-domain analyses of HRV indicated that a low
      frequency (LF) component of HRV was decreased, and a high frequency (HF)
      component of HRV was increased during MTrP compression, while LF/HF ratio was
      decreased during MTrP compression. In addition, prefrontal hemodynamic activity
      was significantly decreased during MTrP compression compared with Non-MTrP
      compression. Furthermore, changes in autonomic activity were significantly
      correlated with changes in subjective pain and prefrontal hemodynamic activity.
      Along with previous studies indicating a role for sympathetic activity in the
      exacerbation of chronic pain, the present results suggest that MTrP compression
      in the neck region alters the activity of the autonomic nervous system via the
      prefrontal cortex to reduce subjective pain.

PMID- 28442988
TI  - Adiponectin Receptors Are Less Sensitive to Stress in a Transgenic Mouse Model of
      Alzheimer's Disease.
AB  - Background: Adiponectin and leptin are implicated in the initiation and
      pathomechanism of Alzheimer's disease (AD). The serum concentrations of these
      adipokines has been extensively studied in AD, however little is known about
      their receptors in this disease. Objective: We developed a novel approach to
      examine whether the receptors of adiponectin (AdipoR1 and -R2) and/or leptin
      (LepR) can contribute to AD pathomechanism. To achieve this, we investigated the
      effect of both genetic and environmental factors associated with AD on the
      expression of these receptors. Method: We used C57BL/6J (WT) and
      APP(swe)/Presen(e9d)1 (AD) mice. Both strains were exposed to restraint stress
      (RS) daily for 6h over different time periods. Then, we measured the mRNA
      expression of AdipoR1, AdipoR2 and LepR and the level of AdipoR1 and AdipoR2
      proteins in the hippocampal and prefrontal cortical areas of each mouse. Results:
      We detected brain region specific transcriptomic changes of adiponectin receptors
      induced by APP and PS1 transgenes. Both acute and chronic RS caused significant
      elevations in AdipoR1 mRNA expression in the hippocampus of WT mice. In the
      prefrontal cortex, the mRNA expression of AdipoR1 followed a biphasic course. In
      AD mice, RS did not promote any changes in the expression of AdipoR1 mRNA and
      AdipoR1 protein levels. AdipoR2 mRNA in AD animals, however, showed a significant
      increase in the prefrontal cortex during RS. Regarding AdipoR1 and AdipoR2 mRNA
      and protein expression, relevant changes could be measured during stress exposure
      in both brain areas. Furthermore, stress exposed groups exhibited little change
      in LepR mRNA expression. Conclusion: Our findings indicate that carrying the
      transgenes associated with AD induces modification in the expression of both
      adiponectin receptors. In the case of a normal genetic background, these
      receptors also appear to be sensitive to environmental factors, while in a
      genetically determined AD model less response to stress stimuli could be
      observed. The results suggest that modification of adipokine receptors could also
      be considered in the therapeutic approach to AD.

PMID- 28442989
TI  - Perinatal Brain Injury As a Consequence of Preterm Birth and Intrauterine
      Inflammation: Designing Targeted Stem Cell Therapies.
AB  - Chorioamnionitis is a major cause of preterm birth and brain injury. Bacterial
      invasion of the chorion and amnion, and/or the placenta, can lead to a fetal
      inflammatory response, which in turn has significant adverse consequences for the
      developing fetal brain. Accordingly, there is a strong causal link between
      chorioamnionitis, preterm brain injury and the pathogenesis of severe postnatal
      neurological deficits and cerebral palsy. Currently there are no treatments to
      protect or repair against brain injury in preterm infants born after pregnancy
      compromised by intrauterine infection. This review describes the injurious
      cascade of events in the preterm brain in response to a severe fetal inflammatory
      event. We will highlight specific periods of increased vulnerability, and the
      potential effects of therapeutic intervention with cell-based therapies. Many
      clinical trials are underway to investigate the efficacy of stem cells to treat
      patients with cerebral palsy. Stem cells, obtained from umbilical cord tissue and
      cord blood, normally discarded after birth, are emerging as a safe and
      potentially effective therapy. It is not yet known, however, which stem cell
      type(s) are the most efficacious for administration to preterm infants to treat
      brain injury-mediated inflammation. Individual stem cell populations found in
      cord blood and tissue, such as mesenchymal stem cells (MSCs) and endothelial
      progenitor cells (EPCs), have a number of potential benefits that may
      specifically target preterm inflammatory-induced brain injury. MSCs have strong
      immunomodulatory potential, protecting against global and local neuroinflammatory
      cascades triggered during infection to the fetus. EPCs have angiogenic and
      vascular reparative qualities that make them ideal for neurovascular repair. A
      combined therapy using both MSCs and EPCs to target inflammation and promote
      angiogenesis for re-establishment of vital vessel networks is a treatment concept
      that warrants further investigation.

PMID- 28442990
TI  - Spatiotemporal and Long Lasting Modulation of 11 Key Nogo Signaling Genes in
      Response to Strong Neuroexcitation.
AB  - Inhibition of nerve growth and plasticity in the CNS is to a large part mediated
      by Nogo-like signaling, now encompassing a plethora of ligands, receptors, co
      receptors and modulators. Here we describe the distribution and levels of mRNA
      encoding 11 key genes involved in Nogo-like signaling (Nogo-A, Oligodendrocyte
      Myelin glycoprotein (OMgp), Nogo receptor 1 (NgR1), NgR2, NgR3, Lingo-1, TNF
      receptor orphan Y (Troy), Olfactomedin, Lateral olfactory tract usher substance
      (Lotus) and membrane-type matrix metalloproteinase-3 (MT3-MPP)), as well as BDNF
      and GAPDH. Expression was analyzed in nine different brain areas before, and at
      eight time points during the first 3 days after a strong neuroexcitatory
      stimulation, caused by one kainic acid injection. A temporo-spatial pattern of
      orderly transcriptional regulations emerges that strengthens the role of Nogo
      signaling mechanisms for synaptic plasticity in synchrony with transcriptional
      increases of BDNF mRNA. For most Nogo-type signaling genes, the largest
      alterations of mRNA levels occur in the dentate gyrus, with marked alterations
      also in the CA1 region. Changes occurred somewhat later in several areas of the
      cerebral cortex. The detailed spatio-temporal pattern of mRNA presence and kainic
      acid-induced transcriptional response is gene-specific. We reveal that several
      different gene alterations combine to decrease (and later increase) Nogo-like
      signaling, as expected to allow structural plasticity responses. Other genes are
      altered in the opposite direction, suggesting that the system prepares in advance
      in order to rapidly restore balance. However, the fact that Lingo-1 shows a
      seemingly opposite, plasticity inhibiting response to kainic acid (strong
      increase of mRNA in the dentate gyrus), may instead suggest a plasticity
      enhancing intracellular function of this presumed NgR1 co-receptor.

PMID- 28442991
TI  - A Novel Long Non-coding RNA, durga Modulates Dendrite Density and Expression of
      kalirin in Zebrafish.
AB  - Kalirin, a key player in axonal development, nerve growth and synaptic re
      modeling, is implicated in many pathological conditions like schizophrenia and
      autism-spectrum disorders. Alternative promoters and splicing lead to
      functionally distinct isoforms, but the post-transcriptional regulation of
      Kalirin has not been studied. Here, we report a novel non-coding RNA, which we
      name durga, arising from the first exon of kalirin a (kalrna) in the antisense
      orientation in zebrafish. The kalrna and durga transcripts are barely detectable
      during early development, but steadily increase by 24 hours post-fertilization
      (hpf) as the brain develops. Over-expression of durga in the zebrafish embryo led
      to an increase in kalrna expression. The morphology of the neurons cultured from
      durga injected embryos had significantly fewer and shorter dendrites. Although
      durga has no apparent sequence homolog in mammals, based on gene synteny, we
      found a non-coding RNA arising from the 5' end of the human Kalrn gene and
      expressed in the human neuronal cell line, SH-SY5Y. We propose that the zebrafish
      lncRNA durga maintains dendritic length and density through regulation of kalrna
      expression and this may have further implications in mammalian systems.

PMID- 28442992
TI  - Genetic Deletion of Akt3 Induces an Endophenotype Reminiscent of Psychiatric
      Manifestations in Mice.
AB  - The protein kinase B (PKB/Akt), found in three distinctive isoforms
      (PKBalpha/Akt1, PKBbeta/Akt2, PKBgamma/Akt3), is implicated in a variety of
      cellular processes such as cell development, growth and survival. Although Akt3
      is the most expressed isoform in the brain, its role in cerebral functions is
      still unclear. In the present study, we investigated the behavioral,
      electrophysiological and biochemical consequences of Akt3 deletion in mice. Motor
      abilities, spatial navigation, recognition memory and LTP are intact in the Akt3
      knockout (KO) mice. However, the prepulse inhibition, three-chamber social,
      forced swim, tail suspension, open field, elevated plus maze and light-dark
      transition tests revealed an endophenotype reminiscent of psychiatric
      manifestations such as schizophrenia, anxiety and depression. Biochemical
      investigations revealed that Akt3 deletion was associated with reduced levels of
      phosphorylated GSK3alpha/beta at serine 21/9 in several brain regions, although
      Akt1 and Akt2 levels were unaffected. Notably, chronic administration of lithium,
      a mood stabilizer, restored the decreased phosphorylated GSK3alpha/beta levels
      and rescued the depressive and anxiety-like behaviors in the Akt3 KO mice.
      Collectively, our data suggest that Akt3 might be a critical molecule underlying
      psychiatric-related behaviors in mice.

PMID- 28442993
TI  - Alcohol-Induced Neuroadaptation Is Orchestrated by the Histone Acetyltransferase
      CBP.
AB  - Homeostatic neural adaptations to alcohol underlie the production of alcohol
      tolerance and the associated symptoms of withdrawal. These adaptations have been
      shown to persist for relatively long periods of time and are believed to be of
      central importance in promoting the addictive state. In Drosophila, a single
      exposure to alcohol results in long-lasting alcohol tolerance and symptoms of
      withdrawal following alcohol clearance. These persistent adaptations involve
      mechanisms such as long-lasting changes in gene expression and perhaps epigenetic
      restructuring of chromosomal regions. Histone modifications have emerged as
      important modulators of gene expression and are thought to orchestrate and
      maintain the expression of multi-gene networks. Previously genes that contribute
      to tolerance were identified as those that show alcohol-induced changes in
      histone H4 acetylation following a single alcohol exposure. However, the
      molecular mediator of the acetylation process that orchestrates their expression
      remains unknown. Here we show that the Drosophila ortholog of mammalian CBP,
      nejire, is the histone acetyltransferase involved in regulatory changes producing
      tolerance-alcohol induces nejire expression, nejire mutations suppress tolerance,
      and transgenic nejire induction mimics tolerance in alcohol-naive animals.
      Moreover, we observed that a loss-of-function mutation in the alcohol tolerance
      gene slo epistatically suppresses the effects of CBP induction on alcohol
      resistance, linking nejire to a well-established alcohol tolerance gene network.
      We propose that CBP is a central regulator of the network of genes underlying an
      alcohol adaptation.

PMID- 28442994
TI  - EGF Enhances Oligodendrogenesis from Glial Progenitor Cells.
AB  - Emerging evidence indicates that epidermal growth factor (EGF) signaling plays a
      positive role in myelin development and repair, but little is known about its
      biological effects on the early generation and differentiation of oligodendrocyte
      (OL) lineage cells. In this study, we investigated the role of EGF in early OL
      development with isolated glial restricted precursor (GRP) cells. It was found
      that EGF collaborated with Platelet Derived Growth Factor-AA (PDGFaa) to promote
      the survival and self-renewal of GRP cells, but predisposed GRP cells to develop
      into O4- early-stage oligodendrocyte precursor cells (OPCs) in the absence of or
      PDGFaa. In OPCs, EGF synergized with PDGFaa to maintain their O4 negative
      antigenic phenotype. Upon PDGFaa withdrawal, EGF promoted the terminal
      differentiation of OPCs by reducing apoptosis and increasing the number of mature
      OLs. Together, these data revealed that EGF is an important mitogen to enhance
      oligodendroglial development.

PMID- 28442995
TI  - MicroRNA-182 Regulates Neurite Outgrowth Involving the PTEN/AKT Pathway.
AB  - MicroRNAs are implicated in neuronal development and maturation. Neuronal
      maturation, including axon outgrowth and dendrite tree formation, is regulated by
      complex mechanisms and related to several neurodevelopmental disorders. We
      demonstrated that one neuron-enriched microRNA, microRNA-182 (miR-182), played a
      significant role in regulating neuronal axon outgrowth and dendrite tree
      formation. Overexpression of miR-182 promoted axon outgrowth and complexity of
      the dendrite tree while also increasing the expression of neurofilament-M and
      neurofilament-L, which provide structural support for neurite outgrowth. However,
      a reduction of miR-182 inhibited neurite outgrowth. Furthermore, we showed that
      miR-182 activated the AKT pathway by increasing AKT phosphorylation on S473 and
      T308 and inhibiting PTEN activity by increasing phosphorylation on S380.
      Inhibition of AKT activity with the PI3-K inhibitor LY294002 could downregulate
      AKT and PTEN phosphorylation and suppress axon outgrowth. In addition, we showed
      that BCAT2 might be the target of miR-182 that takes part in the regulation of
      neuronal maturation; blockage of endogenous BCAT2 promotes axon outgrowth and AKT
      activity. These observations indicate that miR-182 regulates axon outgrowth and
      dendrite maturation involving activation of the PTEN/AKT pathway.

PMID- 28442996
TI  - Structural Characteristics of Simple RNA Repeats Associated with Disease and
      their Deleterious Protein Interactions.
AB  - Short Tandem Repeats (STRs) are frequent entities in many transcripts, however,
      in some cases, pathological events occur when a critical repeat length is
      reached. This phenomenon is observed in various neurological disorders, such as
      myotonic dystrophy type 1 (DM1), fragile X-associated tremor/ataxia syndrome,
      C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia
      (C9ALS/FTD), and polyglutamine diseases, such as Huntington's disease (HD) and
      spinocerebellar ataxias (SCA). The pathological effects of these repeats are
      triggered by mutant RNA transcripts and/or encoded mutant proteins, which depend
      on the localization of the expanded repeats in non-coding or coding regions. A
      growing body of recent evidence revealed that the RNA structures formed by these
      mutant RNA repeat tracts exhibit toxic effects on cells. Therefore, in this
      review article, we present existing knowledge on the structural aspects of
      different RNA repeat tracts as revealed mainly using well-established biochemical
      and biophysical methods. Furthermore, in several cases, it was shown that these
      expanded RNA structures are potent traps for a variety of RNA-binding proteins
      and that the sequestration of these proteins from their normal intracellular
      environment causes alternative splicing aberration, inhibition of nuclear
      transport and export, or alteration of a microRNA biogenesis pathway. Therefore,
      in this review article, we also present the most studied examples of abnormal
      interactions that occur between mutant RNAs and their associated proteins.

PMID- 28442997
TI  - High Spatiotemporal Resolution ECoG Recording of Somatosensory Evoked Potentials
      with Flexible Micro-Electrode Arrays.
AB  - Electrocorticogram (ECoG) has great potential as a source signal, especially for
      clinical BMI. Until recently, ECoG electrodes were commonly used for identifying
      epileptogenic foci in clinical situations, and such electrodes were low-density
      and large. Increasing the number and density of recording channels could enable
      the collection of richer motor/sensory information, and may enhance the precision
      of decoding and increase opportunities for controlling external devices. Several
      reports have aimed to increase the number and density of channels. However, few
      studies have discussed the actual validity of high-density ECoG arrays. In this
      study, we developed novel high-density flexible ECoG arrays and conducted
      decoding analyses with monkey somatosensory evoked potentials (SEPs). Using MEMS
      technology, we made 96-channel Parylene electrode arrays with an inter-electrode
      distance of 700 MUm and recording site area of 350 MUm2. The arrays were mainly
      placed onto the finger representation area in the somatosensory cortex of the
      macaque, and partially inserted into the central sulcus. With electrical finger
      stimulation, we successfully recorded and visualized finger SEPs with a high
      spatiotemporal resolution. We conducted offline analyses in which the stimulated
      fingers and intensity were predicted from recorded SEPs using a support vector
      machine. We obtained the following results: (1) Very high accuracy (~98%) was
      achieved with just a short segment of data (~15 ms from stimulus onset). (2) High
      accuracy (~96%) was achieved even when only a single channel was used. This
      result indicated placement optimality for decoding. (3) Higher channel counts
      generally improved prediction accuracy, but the efficacy was small for
      predictions with feature vectors that included time-series information. These
      results suggest that ECoG signals with high spatiotemporal resolution could
      enable greater decoding precision or external device control.

PMID- 28442998
TI  - Glial Cell Line-Derived Neurotrophic Factor Gene Delivery in Parkinson's Disease:
      A Delicate Balance between Neuroprotection, Trophic Effects, and Unwanted
      Compensatory Mechanisms.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and Neurturin (NRTN) bind to a
      receptor complex consisting of a member of the GDNF family receptor (GFR)-alpha
      and the Ret tyrosine kinase. Both factors were shown to protect nigro-striatal
      dopaminergic neurons and reduce motor symptoms when applied terminally in toxin
      induced Parkinson's disease (PD) models. However, clinical trials based on
      intraputaminal GDNF protein administration or recombinant adeno-associated virus
      (rAAV)-mediated NRTN gene delivery have been disappointing. In this review,
      several factors that could have limited the clinical benefits are discussed.
      Retrograde transport of GDNF/NRTN to the dopaminergic neurons soma is thought to
      be necessary for NRTN/GFR-alpha/Ret signaling mediating the pro-survival effect.
      Therefore, the feasibility of treating advanced patients with neurotrophic
      factors is questioned by recent data showing that: (i) tyrosine hydroxylase
      positive putaminal innervation has almost completely disappeared at 5 years post
      diagnosis and (ii) in patients enrolled in the rAAV-NRTN trial more than 5 years
      post-diagnosis, NRTN was almost not transported to the substantia nigra pars
      compacta. In addition to its anti-apoptotic and neurotrophic properties, GDNF
      also interferes with dopamine homeostasis via time and dose-dependent effects
      such as: stimulation of dopamine neuron excitability, inhibition of dopamine
      transporter activity, tyrosine hydroxylase phosphorylation, and inhibition of
      tyrosine hydroxylase transcription. Depending on the delivery parameters, the net
      result of this intricate network of regulations could be either beneficial or
      deleterious. In conclusion, further unraveling of the mechanism of action of GDNF
      gene delivery in relevant animal models is still needed to optimize the clinical
      benefits of this new therapeutic approach. Recent developments in the design of
      regulated viral vectors will allow to finely adjust the GDNF dose and period of
      administration. Finally, new clinical studies in less advanced patients are
      warranted to evaluate the potential of AAV-mediated neurotrophic factors gene
      delivery in PD. These will be facilitated by the demonstration of the safety of
      rAAV administration into the human brain.

PMID- 28442999
TI  - Roles of Multiple Globus Pallidus Territories of Monkeys and Humans in
      Motivation, Cognition and Action: An Anatomical, Physiological and
      Pathophysiological Review.
AB  - The globus pallidus (GP) communicates with widespread cortical areas that support
      various functions, including motivation, cognition and action. Anatomical tract
      tracing studies revealed that the anteroventral GP communicates with the medial
      prefrontal and orbitofrontal cortices, which are involved in motivational
      control; the anterodorsal GP communicates with the lateral prefrontal cortex,
      which is involved in cognitive control; and the posterior GP communicates with
      the frontal motor cortex, which is involved in action control. This organization
      suggests that distinct subdivisions within the GP play specific roles.
      Neurophysiological studies examining GP neurons in monkeys during behavior
      revealed that the types of information coding performed within these subdivisions
      differ greatly. The anteroventral GP is characterized by activities related to
      motivation, such as reward seeking and aversive avoidance; the anterodorsal GP is
      characterized by activity that reflects cognition, such as goal decision and
      action selection; and the posterior GP is characterized by activity associated
      with action preparation and execution. Pathophysiological studies have shown that
      GABA-related substances or GP lesions result in abnormal activity in the GP,
      which causes site-specific behavioral and motor symptoms. The present review
      article discusses the anatomical organization, physiology and pathophysiology of
      the three major GP territories in nonhuman primates and humans.

PMID- 28443002
TI  - To Wait or Not to Wait-Separate Mechanisms in the Oculomotor Circuit of Basal
      Ganglia.
AB  - We reach a goal immediately after detecting the target, or later by withholding
      the immediate action. Each time, we choose one of these actions by suppressing
      the other. How does the brain control these antagonistic actions? We hypothesized
      that the output of basal ganglia (BG), substantia nigra pars reticulata (SNr),
      suppresses antagonistic oculomotor signals by sending strong inhibitory output to
      superior colliculus (SC). To test this hypothesis, we trained monkeys to perform
      two kinds of saccade task: Immediate (visually guided) and delayed (visually
      withheld but memory-guided) saccade tasks. In both tasks, we applied one
      direction-reward (1DR) procedure to modify the level of goal-reaching motivation.
      We identified SNr neurons that projected to SC by their antidromic activation
      from SC. We stimulated SC on both sides because SNr neurons projecting to the
      ipsilateral SC (ipsiSC) and those projecting to the contralateral SC (contraSC)
      might have antagonistic functions. First, we found that ipsiSC-projecting neurons
      were about 10 times more than contraSC-projecting neurons. More importantly,
      ipsiSC-projecting SNr neurons were roughly divided into two groups which would
      control immediate and delayed saccades separately. The immediate-type SNr neurons
      were clearly inhibited by a visual target on the contralateral side in both
      visual- and memory-1DR tasks. The inhibition would disinhibit SC neurons and
      facilitate a saccade to the contralateral target. This is goal-directed in visual
      1DR task, but is erroneous in memory-1DR task. In contrast, the delayed-type SNr
      neurons tended to be excited by a visual target (especially on the contralateral
      side), which would suppress the immediate saccade to the target. Instead, they
      were inhibited before a delayed (memory-guided) saccade directed to the
      contralateral side, which would facilitate the saccade. ContraSC-projecting SNr
      neurons were more variable with no grouped features, although some of them may
      contribute to the saccade to the ipsilateral target. Finally, we found that some
      ipsiSC-projecting SNr neurons were inhibited more strongly when reward was
      expected, which was associated with shortened saccade reaction times. However,
      many SNr neurons showed no reward-expectation effect. These results suggest that
      two separate oculomotor circuits exist in BG, both of which contribute to goal
      directed behavior, but in different temporal contexts.

PMID- 28443000
TI  - The Olfactory System Revealed: Non-Invasive Mapping by using Constrained
      Spherical Deconvolution Tractography in Healthy Humans.
AB  - Although the olfactory sense has always been considered with less interest than
      the visual, auditive or somatic senses, it does plays a major role in our
      ordinary life, with important implication in dangerous situations or in social
      and emotional behaviors. Traditional Diffusion Tensor signal model and related
      tractography have been used in the past years to reconstruct the cranial nerves,
      including the olfactory nerve (ON). However, no supplementary information with
      regard to the pathways of the olfactory network have been provided. Here, by
      using the more advanced Constrained Spherical Deconvolution (CSD) diffusion
      model, we show for the first time in vivo and non-invasively that, in healthy
      humans, the olfactory system has a widely distributed anatomical network to
      several cortical regions as well as to many subcortical structures. Although the
      present study focuses on an healthy sample size, a similar approach could be
      applied in the near future to gain important insights with regard to the early
      involvement of olfaction in several neurodegenerative disorders.

PMID- 28443001
TI  - Functional Sub-Circuits of the Olfactory System Viewed from the Olfactory Bulb
      and the Olfactory Tubercle.
AB  - Understanding of the olfactory neural circuits has progressed beyond analysis of
      how odor information from the external environment is processed in the brain.
      While spatially-organized sub-circuits were found to exist up to the olfactory
      bulb (OB), the arrangement in the olfactory cortex (OC), especially in its
      representative piriform cortex (PC), appears diffuse and dispersed. An emerging
      view is that the activity of OC neurons may not simply encode odor identity but
      rather encode plastic odor information such as odor value. Although many studies
      support this notion, odor value can be either positive or negative, and the
      existence of sub-circuits corresponding to individual value types is not well
      explored. To address this question, I introduce here two olfactory areas other
      than the PC, OB and olfactory tubercle (OT) whose analysis may facilitate
      understanding of functional sub-circuits related to different odor values.
      Peripheral and centrifugal inputs to the OB are considered to relate to odor
      identity and odor value, respectively and centrifugal inputs to the OB
      potentially represent different odor values during different behavioral periods.
      The OT has spatially-segregated functional domains related to distinct motivated
      and hedonic behaviors. Thus, the OT provides a good starting point from which
      functional sub-circuits across various olfactory regions can be traced. Further
      analysis across wide areas of the olfactory system will likely reveal the
      functional sub-circuits that link odor identity with distinct odor values and
      direct distinct odor-induced motivated and hedonic behaviors.

PMID- 28443003
TI  - Complementary Modular Microcircuits of the Rat Medial Entorhinal Cortex.
AB  - The parahippocampal region is organized into different areas, with the medial
      entorhinal cortex (MEC), presubiculum and parasubiculum prominent in spatial
      memory. Here, we also describe a region at the extremity of the MEC and bordering
      the subicular complex, the medial-most part of the entorhinal cortex. While the
      subdivisions of hippocampus proper form more or less continuous cell sheets, the
      superficial layers of the parahippocampal region have a distinct modular
      architecture. We investigate the spatial distribution, laminar position, and
      putative connectivity of zinc-positive modules in layer 2 of the MEC of rats and
      relate them to the calbindin-positive patches previously described in the
      entorhinal cortex. We found that the zinc-positive modules are complementary to
      the previously described calbindin-positive patches. We also found that inputs
      from the presubiculum are directed toward the zinc-positive modules while the
      calbindin-positive patches received inputs from the parasubiculum. Notably, the
      dendrites of neurons from layers 3 and 5, positive for Purkinje Cell Protein 4
      expression, overlap with the zinc modules. Our data thus indicate that these two
      complementary modular systems, the calbindin patches and zinc modules, are part
      of parallel information streams in the hippocampal formation.

PMID- 28443004
TI  - Assessing Somatosensory Utilization during Unipedal Postural Control.
AB  - Multisensory-visual, vestibular and somatosensory information is integrated for
      appropriate postural control. The primary goal of this study was to assess
      somatosensory utilization during a functional motor task of unipedal postural
      control, in normal healthy adults. Assessing individual bias in the utilization
      of individual sensory contributions during postural control may help
      customization of rehabilitation protocols. In this study, a test paradigm of
      unipedal stance control in supine orientation with and without vision was
      assessed. Postural control in this test paradigm was hypothesized to utilize
      predominantly contributions of somatosensory information from the feet and ankle
      joint, with minimal vestibular input. Fourteen healthy subjects "stood" supine on
      their dominant leg while strapped to a backpack frame that was freely moving on
      air-bearings, to remove available otolith tilt cues with respect to gravity that
      influences postural control when standing upright. The backpack was attached
      through a cable to a pneumatic cylinder that provided a gravity-like load.
      Subjects performed three trials each with Eyes-open (EO) and Eyes-closed (EC)
      while loaded with 60% body weight. There was no difference in unipedal stance
      time (UST) across the two conditions with EC condition challenging the postural
      control system greater than the EO condition. Stabilogram-diffusion analysis
      (SDA) indicated that the critical mean square displacement was significantly
      different between the two conditions. Vestibular cues, both in terms of magnitude
      and the duration for which relevant information was available for postural
      control in this test paradigm, were minimized. These results support our
      hypothesis that maintaining unipedal stance in supine orientation without vision,
      minimizes vestibular contribution and thus predominantly utilizes somatosensory
      information for postural control.

PMID- 28443005
TI  - Waking Up Buried Memories of Old TV Programs.
AB  - Although it has been demonstrated that visual and auditory stimuli can be
      recalled decades after the initial exposure, previous studies have generally not
      ruled out the possibility that the material may have been seen or heard during
      the intervening period. Evidence shows that reactivations of a long-term memory
      trace play a role in its update and maintenance. In the case of remote or very
      long-term memories, it is most likely that these reactivations are triggered by
      the actual re-exposure to the stimulus. In this study we decided to explore
      whether it is possible to recall stimuli that could not have been re-experienced
      in the intervening period. We tested the ability of French participants (N = 34,
      31 female) to recall 50 TV programs broadcast on average for the last time 44
      years ago (from the 60's and early 70's). Potential recall was elicited by the
      presentation of short audiovisual excerpts of these TV programs. The absence of
      potential re-exposure to the material was strictly controlled by selecting TV
      programs that have never been rebroadcast and were not available in the public
      domain. Our results show that six TV programs were particularly well identified
      on average across the 34 participants with a median percentage of 71.7% (SD =
      13.6, range: 48.5-87.9%). We also obtained 50 single case reports with associated
      information about the viewing of 23 TV programs including the 6 previous ones.
      More strikingly, for two cases, retrieval of the title was made spontaneously
      without the need of a four-proposition choice. These results suggest that re
      exposures to the stimuli are not necessary to maintain a memory for a lifetime.
      These new findings raise fundamental questions about the underlying mechanisms
      used by the brain to store these very old sensory memories.

PMID- 28443006
TI  - Cognitive Resources Necessary for Motor Control in Older Adults Are Reduced by
      Walking and Coordination Training.
AB  - We examined if physical exercise interventions were effective to reduce cognitive
      brain resources recruited while performing motor control tasks in older adults.
      Forty-three older adults (63-79 years of age) participated in either a walking (n
      = 17) or a motor coordination (n = 15) intervention (1 year, 3 times per week) or
      were assigned to a control group (n = 11) doing relaxation and stretching
      exercises. Pre and post the intervention period, we applied functional MRI to
      assess brain activation during imagery of forward and backward walking and during
      counting backwards from 100 as control task. In both experimental groups,
      activation in the right dorsolateral prefrontal cortex (DLPFC) during imagery of
      forward walking decreased from pre- to post-test (Effect size: -1.55 and -1.16
      for coordination and walking training, respectively; Cohen's d). Regression
      analysis revealed a significant positive association between initial motor status
      and activation change in the right DLPFC (R2 = 0.243, F(3,39) = 4.18, p = 0.012).
      Participants with lowest motor status at pretest profited most from the
      interventions. Data suggest that physical training in older adults is effective
      to free up cognitive resources otherwise needed for the control of locomotion.
      Training benefits may become particularly apparent in so-called dual-task
      situations where subjects must perform motor and cognitive tasks concurrently.

PMID- 28443008
TI  - Against Strong Ethical Parity: Situated Cognition Theses and Transcranial Brain
      Stimulation.
AB  - According to a prominent suggestion in the ethics of transcranial
      neurostimulation the effects of such devices can be treated as ethically on par
      with established, pre-neurotechnological alterations of the mind. This parity
      allegedly is supported by situated cognition theories showing how external
      devices can be part of a cognitive system. This article will evaluate this
      suggestion. It will reject the claim, that situated cognition theories support
      ethical parity. It will however point out another reason, why external carriers
      or modifications of the mental might come to be considered ethically on par with
      internal carriers. Section "Why Could There Be Ethical Parity between Neural
      Tissue and External Tools?" presents the ethical parity theses between external
      and internal carriers of the mind as well as neurotechnological alterations and
      established alterations. Section "Extended, Embodied, Embedded: Situated
      Cognition as a Relational Thesis" will elaborate the different situated cognition
      approaches and their relevance for ethics. It will evaluate, whether transcranial
      stimulation technologies are plausible candidates for situated cognition theses.
      Section "On the Ethical Relevance of Situated Cognition Theses" will discuss
      criteria for evaluating whether a cognitive tool is deeply embedded with a
      cognitive system and apply these criteria to transcranial brain stimulation
      technologies. Finally it will discuss the role diverse versions of situated
      cognition theory can play in the ethics of altering mental states, especially the
      ethics of transcranial brain stimulation technologies.

PMID- 28443007
TI  - Neuroimaging of Human Balance Control: A Systematic Review.
AB  - This review examined 83 articles using neuroimaging modalities to investigate the
      neural correlates underlying static and dynamic human balance control, with aims
      to support future mobile neuroimaging research in the balance control domain.
      Furthermore, this review analyzed the mobility of the neuroimaging hardware and
      research paradigms as well as the analytical methodology to identify and remove
      movement artifact in the acquired brain signal. We found that the majority of
      static balance control tasks utilized mechanical perturbations to invoke feet-in
      place responses (27 out of 38 studies), while cognitive dual-task conditions were
      commonly used to challenge balance in dynamic balance control tasks (20 out of 32
      studies). While frequency analysis and event related potential characteristics
      supported enhanced brain activation during static balance control, that in
      dynamic balance control studies was supported by spatial and frequency analysis.
      Twenty-three of the 50 studies utilizing EEG utilized independent component
      analysis to remove movement artifacts from the acquired brain signals. Lastly,
      only eight studies used truly mobile neuroimaging hardware systems. This review
      provides evidence to support an increase in brain activation in balance control
      tasks, regardless of mechanical, cognitive, or sensory challenges. Furthermore,
      the current body of literature demonstrates the use of advanced signal processing
      methodologies to analyze brain activity during movement. However, the static
      nature of neuroimaging hardware and conventional balance control paradigms
      prevent full mobility and limit our knowledge of neural mechanisms underlying
      balance control.

PMID- 28443009
TI  - Behavioral and Brain Measures of Phasic Alerting Effects on Visual Attention.
AB  - In the present study, we investigated effects of phasic alerting on visual
      attention in a partial report task, in which half of the displays were preceded
      by an auditory warning cue. Based on the computational Theory of Visual Attention
      (TVA), we estimated parameters of spatial and non-spatial aspects of visual
      attention and measured event-related lateralizations (ERLs) over visual
      processing areas. We found that the TVA parameter sensory effectiveness a, which
      is thought to reflect visual processing capacity, significantly increased with
      phasic alerting. By contrast, the distribution of visual processing resources
      according to task relevance and spatial position, as quantified in parameters top
      down control alpha and spatial bias windex, was not modulated by phasic alerting.
      On the electrophysiological level, the latencies of ERLs in response to the task
      displays were reduced following the warning cue. These results suggest that
      phasic alerting facilitates visual processing in a general, unselective manner
      and that this effect originates in early stages of visual information processing.

PMID- 28443010
TI  - Enhanced Functional Connectivity between the Bilateral Primary Motor Cortices
      after Acupuncture at Yanglingquan (GB34) in Right-Hemispheric Subcortical Stroke
      Patients: A Resting-State fMRI Study.
AB  - Increasing neuroimaging researches in stroke rehabilitation had revealed the
      neural mechanisms of rehabilitation therapy. However, little was known about the
      neural mechanisms of acupuncture therapy in subcortical stroke patients. The aim
      of this study was to investigate the changes of functional connectivity (FC)
      between the bilateral primary motor cortices (M1s) after acupuncture intervention
      in right subcortical stroke patients. Twenty right-hemispheric subcortical stroke
      patients and 20 healthy subjects were recruited to undergo one functional
      magnetic resonance imaging (fMRI) scanning. The scanning consisted of resting
      state fMRI before and after needling at Yanglinquan (GB34), and task-evoked fMRI.
      The most significant active point during the left passive thumb-to-index task was
      chosen as the seed point. The seed-based FC analysis of the bilateral M1s was
      performed. Stroke patients revealed decreased FC between the bilateral M1s
      compared with healthy subjects, and the decreased FC was significantly enhanced
      after acupuncture at GB34. Acupuncture could increase the intrinsically decreased
      FC between the bilateral M1s which provided further insight into the neural
      mechanisms of acupuncture for motor function recovery in stroke patients.

PMID- 28443012
TI  - The Posterior Parietal Cortex Subserves Precise Motor Timing in Professional
      Drummers.
AB  - The synchronization task is a well-established paradigm for the investigation of
      motor timing with respect to an external pacing signal. It requires subjects to
      synchronize their finger taps in synchrony with a regular metronome. A specific
      significance of the posterior parietal cortex (PPC) for superior synchronization
      in professional drummers has been suggested. In non-musicians, modulation of the
      excitability of the left PPC by means of transcranial direct current stimulation
      (tDCS) modulates synchronization performance of the right hand. In order to
      determine the significance of the left PPC for superior synchronization in
      drummers, we here investigate the effects of cathodal and anodal tDCS in 20
      professional drummers on auditory-motor synchronization of the right hand. A
      continuation and a reaction time task served as control conditions. Moreover, the
      interaction between baseline performance and tDCS polarity was estimated in
      precise as compared to less precise synchronizers according to median split.
      Previously published data from 16 non-musicians were re-analyzed accordingly in
      order to highlight possible differences of tDCS effects in drummers and non
      musicians. TDCS was applied for 10 min with an intensity of 0.25 mA over the left
      PPC. Behavioral measures were determined prior to and immediately after tDCS. In
      drummers the overall analysis of synchronization performance revealed
      significantly larger tap-to-tone asynchronies following anodal tDCS with the tap
      preceding the tone replicating findings in non-musicians. No significant effects
      were found on control tasks. The analysis for participants with large as compared
      to small baseline asynchronies revealed that only in drummers with small
      asynchronies tDCS interfered with synchronization performance. The re-analysis of
      the data from non-musicians indicated the reversed pattern. The data support the
      hypothesis that the PPC is involved in auditory-motor synchronization and extend
      previous findings by showing that its functional significance varies with musical
      expertise.

PMID- 28443013
TI  - Pypes: Workflows for Processing Multimodal Neuroimaging Data.

PMID- 28443011
TI  - The Lateral Occipito-temporal Cortex Is Involved in the Mental Manipulation of
      Body Part Imagery.
AB  - The lateral occipito-temporal cortex (LOTC), including the extrastriate body
      area, is known to be involved in the perception of body parts. Although still
      controversial, recent studies have demonstrated the role of the LOTC in higher
      level body-related cognition in humans. This study consisted of two experiments
      (E1 and E2). The first (E1) was an exploratory experiment to find the neural
      correlate of the mental manipulation of body part imagery, in which brain
      cerebral glucose metabolic rates and the performance of mental rotation of the
      hand were measured in 100 subjects who exhibited a range of symptoms of cognitive
      decline. In E1, we found that the level of glucose metabolism in the right LOTC
      was significantly correlated with performance in a task involving mental
      manipulation of the hand. Next, in E2, we performed a randomized, double-blind,
      controlled intervention study (clinical trial number: UMIN 000018310) in younger
      healthy adults to test whether right occipital (corresponding to the right LOTC)
      anodal stimulation using transcranial direct current stimulation (tDCS) could
      enhance the mental manipulation of the hand. In E2, we demonstrated a significant
      effect of tDCS on the accuracy rate in a task involving mental manipulation of
      the hand. Although further study is necessary to answer the question of whether
      these results are specific for the mental manipulation of body parts but not non
      body parts, E1 demonstrated a possible role of the LOTC in carrying out the body
      mental manipulation task in patients with dementia, and E2 suggested the possible
      effect of tDCS on this task in healthy subjects.

PMID- 28443015
TI  - Cross-Subject EEG Feature Selection for Emotion Recognition Using Transfer
      Recursive Feature Elimination.
AB  - Using machine-learning methodologies to analyze EEG signals becomes increasingly
      attractive for recognizing human emotions because of the objectivity of
      physiological data and the capability of the learning principles on modeling
      emotion classifiers from heterogeneous features. However, the conventional
      subject-specific classifiers may induce additional burdens to each subject for
      preparing multiple-session EEG data as training sets. To this end, we developed a
      new EEG feature selection approach, transfer recursive feature elimination (T
      RFE), to determine a set of the most robust EEG indicators with stable
      geometrical distribution across a group of training subjects and a specific
      testing subject. A validating set is introduced to independently determine the
      optimal hyper-parameter and the feature ranking of the T-RFE model aiming at
      controlling the overfitting. The effectiveness of the T-RFE algorithm for such
      cross-subject emotion classification paradigm has been validated by DEAP
      database. With a linear least square support vector machine classifier
      implemented, the performance of the T-RFE is compared against several
      conventional feature selection schemes and the statistical significant
      improvement has been found. The classification rate and F-score achieve 0.7867,
      0.7526, 0.7875, and 0.8077 for arousal and valence dimensions, respectively, and
      outperform several recent reported works on the same database. In the end, the T
      RFE based classifier is compared against two subject-generic classifiers in the
      literature. The investigation of the computational time for all classifiers
      indicates the accuracy improvement of the T-RFE is at the cost of the longer
      training time.

PMID- 28443014
TI  - The Topographical Mapping in Drosophila Central Complex Network and Its Signal
      Routing.
AB  - Neural networks regulate brain functions by routing signals. Therefore,
      investigating the detailed organization of a neural circuit at the cellular
      levels is a crucial step toward understanding the neural mechanisms of brain
      functions. To study how a complicated neural circuit is organized, we analyzed
      recently published data on the neural circuit of the Drosophila central complex,
      a brain structure associated with a variety of functions including sensory
      integration and coordination of locomotion. We discovered that, except for a
      small number of "atypical" neuron types, the network structure formed by the
      identified 194 neuron types can be described by only a few simple mathematical
      rules. Specifically, the topological mapping formed by these neurons can be
      reconstructed by applying a generation matrix on a small set of initial neurons.
      By analyzing how information flows propagate with or without the atypical
      neurons, we found that while the general pattern of signal propagation in the
      central complex follows the simple topological mapping formed by the "typical"
      neurons, some atypical neurons can substantially re-route the signal pathways,
      implying specific roles of these neurons in sensory signal integration. The
      present study provides insights into the organization principle and signal
      integration in the central complex.

PMID- 28443016
TI  - Genetics of Aggression in Alzheimer's Disease (AD).
AB  - Alzheimer's disease (AD) is a terminal, age-related neurological syndrome
      exhibiting progressive cognitive and memory decline, however AD patients in
      addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include
      aggression. In this communication we provide recent evidence for the mis
      regulation of a small family of genes expressed in the human hippocampus that
      appear to be significantly involved in expression patterns common to both AD and
      aggression. DNA array- and mRNA transcriptome-based gene expression analysis and
      candidate gene association and/or genome-wide association studies (CGAS, GWAS) of
      aggressive attributes in humans have revealed a surprisingly small subset of six
      brain genes that are also strongly associated with altered gene expression
      patterns in AD. These genes encoded on five different chromosomes (chr) include
      the androgen receptor (AR; chrXq12), brain-derived neurotrophic factor (BDNF;
      chr11p14.1), catechol-O-methyl transferase (COMT; chr22q11.21), neuronal specific
      nitric oxide synthase (NOS1; chr12q24.22), dopamine beta-hydroxylase (DBH
      chr9q34.2) and tryptophan hydroxylase (TPH1, chr11p15.1 and TPH2, chr12q21.1).
      Interestingly, (i) the expression of three of these six genes (COMT, DBH, NOS1)
      are highly variable; (ii) three of these six genes (COMT, DBH, TPH1) are involved
      in DA or serotonin metabolism, biosynthesis and/or neurotransmission; and (iii)
      five of these six genes (AR, BDNF, COMT, DBH, NOS1) have been implicated in the
      development, onset and/or propagation of schizophrenia. The magnitude of the
      expression of genes implicated in aggressive behavior appears to be more
      pronounced in the later stages of AD when compared to MCI. These recent genetic
      data further indicate that the extent of cognitive impairment may have some
      bearing on the degree of aggression which accompanies the AD phenotype.

PMID- 28443017
TI  - Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition.
AB  - Contrary to the known benefits from a moderate dietary reduction during adulthood
      on life span and health, maternal nutrient reduction during pregnancy is supposed
      to affect the developing brain, probably resulting in impaired brain structure
      and function throughout life. Decreased fetal nutrition delivery is widespread in
      both developing and developed countries, caused by poverty and natural disasters,
      but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35
      years of age, placental insufficiency, or multiples. Compromised development of
      fetal cerebral structures was already shown in our baboon model of moderate
      maternal nutrient reduction. The present study was designed to follow-up and
      evaluate the effects of moderate maternal nutrient reduction on individual brain
      aging in the baboon during young adulthood (4-7 years; human equivalent 14-24
      years), applying a novel, non-invasive neuroimaging aging biomarker. The study
      reveals premature brain aging of +2.7 years (p < 0.01) in the female baboon
      exposed to fetal undernutrition. The effects of moderate maternal nutrient
      reduction on individual brain aging occurred in the absence of fetal growth
      restriction or marked maternal weight reduction at birth, which stresses the
      significance of early nutritional conditions in life-long developmental
      programming. This non-invasive MRI biomarker allows further longitudinal in vivo
      tracking of individual brain aging trajectories to assess the life-long effects
      of developmental and environmental influences in programming paradigms, aiding
      preventive and curative treatments on cerebral atrophy in experimental animal
      models and humans.

PMID- 28443018
TI  - The Treatment Based on Temporal Information Processing Reduces Speech
      Comprehension Deficits in Aphasic Subjects.
AB  - Experimental studies have reported a close association between temporal
      information processing (TIP) and language comprehension. Brain-injured subjects
      with aphasia show disturbed TIP which was evidenced in elevated temporal order
      threshold (TOT) as compared to control subjects. The present study is aimed at
      improving auditory speech comprehension in aphasic subjects using a specific
      temporal treatment. Fourteen patients having deficits in both speech
      comprehension and TIP were tested. The Token Test, phoneme discrimination tests
      (PDT) and Voice-Onset-Time (VOT) Test were employed to assess speech
      comprehension. The TOT was measured using two 10 ms tones (400 Hz, 3000 Hz)
      presented binaurally. The patients participated in eight 45-min sessions of
      either the specific temporal treatment (n = 7) aimed at improving the perception
      of sequencing abilities, or in a non-temporal control treatment (n = 7) on volume
      discrimination. The temporal treatment yielded an improvement in TIP. Moreover, a
      transfer of improvement from the time domain to the language domain was observed.
      The control treatment did not improve either TIP or speech comprehension in any
      of the applied tests.

PMID- 28443019
TI  - Increased Diagnostic Accuracy of Digital vs. Conventional Clock Drawing Test for
      Discrimination of Patients in the Early Course of Alzheimer's Disease from
      Cognitively Healthy Individuals.
AB  - The conventional Clock Drawing Test (cCDT) is a rapid and inexpensive screening
      tool for detection of moderate and severe dementia. However, its usage is limited
      due to poor diagnostic accuracy especially in patients with mild cognitive
      impairment (MCI). The diagnostic value of a newly developed digital Clock Drawing
      Test (dCDT) was evaluated and compared with the cCDT in 20 patients with early
      dementia due to AD (eDAT), 30 patients with amnestic MCI (aMCI) and 20
      cognitively healthy controls (HCs). Parameters assessed by dCDT were time while
      transitioning the stylus from one stroke to the next above the surface (i.e.,
      time-in-air), time the stylus produced a visible stroke (i.e., time-on-surface)
      and total-time during clock drawing. Receiver-operating characteristic (ROC)
      curves were calculated and logistic regression analyses have been conducted for
      statistical analysis. Using dCDT, time-in-air was significantly increased in eDAT
      (70965.8 ms) compared to aMCI (54073.7 ms; p = 0.027) and HC (32315.6 ms; p <
      0.001). In addition, time-in-air was significantly longer in patients with aMCI
      compared to HC (p = 0.003), even in the aMCI group with normal cCDT score
      (54141.8 ms; p < 0.001). Time-in-air using dCDT allowed discrimination of
      patients with aMCI from HCs with a sensitivity of 81.3% and a specificity of
      72.2% while cCDT scoring revealed a sensitivity of 62.5% and a specificity of
      83.3%. Most interestingly, time-in-air allowed even discrimination of aMCI
      patients with normal cCDT scores (80% from all aMCI patients) from HCs with a
      clinically relevant sensitivity of 80.8% and a specificity of 77.8%. A
      combination of dCDT variables and cCDT scores did not improve the discrimination
      of patients with aMCI from HC. In conclusion, assessment of time-in-air using
      dCDT yielded a higher diagnostic accuracy for discrimination of aMCI patients
      from HCs than the use of cCDT even in those aMCI patients with normal cCDT
      scores. Modern digitizing devices offer the opportunity to measure subtle changes
      of visuo-constructive demands and executive functions that may be used as a fast
      and easy to perform screening instrument for the early detection of cognitive
      impairment in primary care.

PMID- 28443020
TI  - BGP-15 Protects against Oxaliplatin-Induced Skeletal Myopathy and Mitochondrial
      Reactive Oxygen Species Production in Mice.
AB  - Chemotherapy is a leading intervention against cancer. Albeit highly effective,
      chemotherapy has a multitude of deleterious side-effects including skeletal
      muscle wasting and fatigue, which considerably reduces patient quality of life
      and survivability. As such, a defense against chemotherapy-induced skeletal
      muscle dysfunction is required. Here we investigate the effects of oxaliplatin
      (OXA) treatment in mice on the skeletal muscle and mitochondria, and the capacity
      for the Poly ADP-ribose polymerase (PARP) inhibitor, BGP-15, to ameliorate any
      pathological side-effects induced by OXA. To do so, we investigated the effects
      of 2 weeks of OXA (3 mg/kg) treatment with and without BGP-15 (15 mg/kg). OXA
      induced a 15% (p < 0.05) reduction in lean tissue mass without significant
      changes in food consumption or energy expenditure. OXA treatment also altered the
      muscle architecture, increasing collagen deposition, neutral lipid and Ca2+
      accumulation; all of which were ameliorated with BGP-15 adjunct therapy. Here, we
      are the first to show that OXA penetrates the mitochondria, and, as a possible
      consequence of this, increases mtROS production. These data correspond with
      reduced diameter of isolated FDB fibers and shift in the fiber size distribution
      frequency of TA to the left. There was a tendency for reduction in intramuscular
      protein content, albeit apparently not via Murf1 (atrophy)- or p62 (autophagy)-
      dependent pathways. BGP-15 adjunct therapy protected against increased ROS
      production and improved mitochondrial viability 4-fold and preserved fiber
      diameter and number. Our study highlights BGP-15 as a potential adjunct therapy
      to address chemotherapy-induced skeletal muscle and mitochondrial pathology.

PMID- 28443022
TI  - Evaluating Quality of Decision-Making Processes in Medicines' Development,
      Regulatory Review, and Health Technology Assessment: A Systematic Review of the
      Literature.
AB  - Introduction: Although pharmaceutical companies, regulatory authorities, and
      health technology assessment (HTA) agencies have been increasingly using decision
      making frameworks, it is not certain whether these enable better quality decision
      making. This could be addressed by formally evaluating the quality of decision
      making process within those organizations. The aim of this literature review was
      to identify current techniques (tools, questionnaires, surveys, and studies) for
      measuring the quality of the decision-making process across the three
      stakeholders. Methods: Using MEDLINE, Web of Knowledge, and other Internet-based
      search engines, a literature review was performed to systematically identify
      techniques for assessing quality of decision making in medicines development,
      regulatory review, and HTA. A structured search was applied using key words and a
      secondary review was carried out. In addition, the measurement properties of each
      technique were assessed and compared. Ten Quality Decision-Making Practices
      (QDMPs) developed previously were then used as a framework for the evaluation of
      techniques identified in the review. Due to the variation in studies identified,
      meta-analysis was inappropriate. Results: This review identified 13 techniques,
      where 7 were developed specifically to assess decision making in medicines'
      development, regulatory review, or HTA; 2 examined corporate decision making, and
      4 general decision making. Regarding how closely each technique conformed to the
      10 QDMPs, the 13 techniques assessed a median of 6 QDMPs, with a mode of 3 QDMPs.
      Only 2 techniques evaluated all 10 QDMPs, namely the Organizational IQ and the
      Quality of Decision Making Orientation Scheme (QoDoS), of which only one
      technique, QoDoS could be applied to assess decision making of both individuals
      and organizations, and it possessed generalizability to capture issues relevant
      to companies as well as regulatory authorities. Conclusion: This review confirmed
      a general paucity of research in this area, particularly regarding the
      development and systematic application of techniques for evaluating quality
      decision making, with no consensus around a gold standard. This review has
      identified QoDoS as the most promising available technique for assessing decision
      making in the lifecycle of medicines and the next steps would be to further test
      its validity, sensitivity, and reliability.

PMID- 28443021
TI  - Functional and Biochemical Endothelial Profiling In Vivo in a Murine Model of
      Endothelial Dysfunction; Comparison of Effects of 1-Methylnicotinamide and
      Angiotensin-converting Enzyme Inhibitor.
AB  - Although it is known that 1-methylnicotinamide (MNA) displays vasoprotective
      activity in mice, as yet the effect of MNA on endothelial function has not been
      demonstrated in vivo. Here, using magnetic resonance imaging (MRI) we profile the
      effects of MNA on endothelial phenotype in mice with atherosclerosis (ApoE/LDLR-/
      ) in vivo, in comparison to angiotensin (Ang) -converting enzyme (ACE) inhibitor
      (perindopril), with known vasoprotective activity. On a biochemical level, we
      analyzed whether MNA- or perindopril-induced improvement in endothelial function
      results in changes in ACE/Ang II-ACE2/Ang-(1-7) balance, and L
      arginine/asymmetric dimethylarginine (ADMA) ratio. Endothelial function and
      permeability were evaluated in the brachiocephalic artery (BCA) in 4-month-old
      ApoE/LDLR-/- mice that were non-treated or treated for 1 month or 2 months with
      either MNA (100 mg/kg/day) or perindopril (10 mg/kg/day). The 3D
      IntraGate(r)FLASH sequence was used for evaluation of BCA volume changes
      following acetylcholine (Ach) administration, and for relaxation time (T1)
      mapping around BCA to assess endothelial permeability using an intravascular
      contrast agent. Activity of ACE/Ang II and ACE2/Ang-(1-7) pathways as well as
      metabolites of L-arginine/ADMA pathway were measured using liquid
      chromatography/mass spectrometry-based methods. In non-treated 6-month-old
      ApoE/LDLR-/- mice, Ach induced a vasoconstriction in BCA that amounted to -7.2%.
      2-month treatment with either MNA or perindopril resulted in the reversal of
      impaired Ach-induced response to vasodilatation (4.5 and 5.5%, respectively) and
      a decrease in endothelial permeability (by about 60% for MNA-, as well as
      perindopril-treated mice). Improvement of endothelial function by MNA and
      perindopril was in both cases associated with the activation of ACE2/Ang-(1-7)
      and the inhibition of ACE/Ang II axes as evidenced by an approximately twofold
      increase in Ang-(1-9) and Ang-(1-7) and a proportional decrease in Ang II and its
      active metabolites. Finally, MNA and perindopril treatment resulted in an
      increase in L-arginine/ADMA ratio by 107% (MNA) and 140% (perindopril), as
      compared to non-treated mice. Functional and biochemical endothelial profiling in
      ApoE/LDLR-/- mice in vivo revealed that 2-month treatment with MNA (100
      mg/kg/day) displayed a similar profile of vasoprotective effect as 2-month
      treatment with perindopril (10 mg/kg/day): i.e., the improvement in endothelial
      function that was associated with the beneficial changes in ACE/Ang II-ACE2/Ang
      (1-7) balance and in L-arginine/ADMA ratio in plasma.

PMID- 28443023
TI  - Inhibition of VEGF and Angiopoietin-2 to Reduce Brain Metastases of Breast Cancer
      Burden.
AB  - For metastases in the central nervous system, angiogenesis enhances metastatic
      potential and promotes progression. Primary factors which drive vessel growth are
      vascular endothelial growth factor (VEGF) and angiopoietin-2. Preclinical models
      show inhibition of either factor reduces metastases spread and inhibits growth.
      This work sets out to answer two questions in a preclinical mouse model. First,
      whether the combined inhibition of VEGF and angiopoietin-2, reduces passive
      permeability and limits drug uptake into brain metastases; and second, whether
      this inhibition reduces metastases burden in brain. We observed combinatorial
      inhibition of VEGF and angiopoietin-2, decreased (p < 0.05) angiogenesis and
      vascular branching in an aortic ring assay and decreased (p < 0.05) endothelial
      wound closure times. Using a brain metastases of breast cancer model (induced by
      intracardiac injections of brain seeking MDA-MB-231Br cells or 4T1Br cells), we
      observed, similar to VEGF, angiopoetin-2 expression correlates to increased
      angiogenesis (p < 0.05) and increased lesion permeability. To determine efficacy,
      animals were administered bevacizumab plus L1-10 (angiopoietin inhibitor) twice
      per week until neurological symptoms developed. Lesion permeability significantly
      decreased by ~50% (p < 0.05) compared to untreated lesions, but remained ~25%
      greater (p < 0.0%) than brain. In subsequent experiments, animals were
      administered similar regimens but sacrificed on day 32. The number of metastatic
      lesions developed was significantly (p < 0.001) reduced in the bevacizumab group
      (56%) and combination group (86%). Lesions' size was reduced in bevacizumab
      treated lesions (~67%) and bevacizumab and L1-10 treated lesions (~78%)
      developing area < 0.5 mm2. In summary, combinatorial inhibition of VEGF and
      angiopoietin reduces lesion permeability and brain metastatic burden.

PMID- 28443024
TI  - Low-Dose of Bergamot-Derived Polyphenolic Fraction (BPF) Did Not Improve
      Metabolic Parameters in Second Generation Antipsychotics-Treated Patients:
      Results from a 60-days Open-Label Study.
AB  - Objectives: The nutraceutical approach to the management of metabolic syndrome
      (MetS) might be a promising strategy in the prevention of cardio-metabolic risk.
      Low-dose bergamot-derived polyphenolic fraction (BPF) has been proven effective
      in patients with MetS, as demonstrated by a concomitant improvement in lipemic
      and glycemic profiles. The present study was aimed to further explore, in a
      sample of subjects receiving second generation antipsychotics (SGAs), the effects
      on body weight and metabolic parameters of a low dose of BPF (500 mg/day)
      administered for 60 days. Methods: Twenty-eight outpatients treated with SGAs
      assumed BPF at single daily dose of 500 mg/day for 60 days. Body weight, BMI,
      fasting levels of glucose, total cholesterol, high density lipoprotein
      cholesterol, low density lipoprotein cholesterol and triglycerides were
      determined; moreover, Brief Psychiatric Rating Scale (BPRS) was administered.
      Results: Low-dose BPF administration did not change clinical and metabolic
      parameters, as well as clinical symptoms in the study sample. At the end of the
      trial, among completers (n = 24) only nine patients (37.5%) reached an LDL
      reduction >0 but <50%. Conclusions: Our results demonstrate that patients treated
      with SGAs may need higher BPF doses for obtaining the positive effects on body
      weight and metabolic parameters previously found in the general population at
      lower doses.

PMID- 28443025
TI  - Honokiol Induces Apoptosis, G1 Arrest, and Autophagy in KRAS Mutant Lung Cancer
      Cells.
AB  - Aberrant signaling transduction induced by mutant KRAS proteins occurs in 20~30%
      of non-small cell lung cancer (NSCLC), however, a direct and effective
      pharmacological inhibitor targeting KRAS has not yet reached the clinic to date.
      Honokiol, a small molecular polyphenol natural biophenolic compound derived from
      the bark of magnolia trees, exerts anticancer activity, however, its mechanism
      remains unknown. In this study, we sought to investigate the in vitro effects of
      honokiol on NSCLC cell lines harboring KRAS mutations. Honokiol was shown to
      induce G1 arrest and apoptosis to inhibit the growth of KRAS mutant lung cancer
      cells, which was weakened by an autophagy inhibitor 3-methyladenine (3-MA),
      suggesting a pro-apoptotic role of honokiol-induced autophagy that was dependent
      on AMPK-mTOR signaling pathway. In addition, we also discovered that Sirt3 was
      significantly up-regulated in honokiol treated KRAS mutant lung cancer cells,
      leading to destabilization of its target gene Hif-1alpha, which indicated that
      the anticancer property of honokiol maybe regulated via a novel mechanism
      associated with the Sirt3/Hif-1alpha. Taken together, these results broaden our
      understanding of the mechanisms on honokiol effects in lung cancer, and reinforce
      the possibility of its potential anticancer benefit as a popular Chinese herbal
      medicine (CHM).

PMID- 28443026
TI  - Short-Term Effects of Lupin vs. Whey Supplementation on Glucose and Insulin
      Responses to a Standardized Meal in a Randomized Cross-Over Trial.
AB  - Background: Whey protein is known to reduce postprandial glycaemia in people with
      type 2 diabetes mellitus. Lupin as a vegetable source of protein could be
      considered as an alternative, as the percentage of vegetarian and vegan consumers
      is raising. The present study compares the acute glycemic effects of whey and
      lupin in healthy volunteers following a carbohydrate-rich reference meal. Methods
      In cross-over design, three standardized meals (reference meal; reference meal +
      whey; reference meal + lupin) were provided to 12 healthy male and female
      volunteers, aged between 23 and 33, in a balanced, randomized order. Volunteers'
      blood glucose and insulin concentrations were analyzed at baseline and at seven
      time points following the ingestion of the meals. Results: The supplementation of
      whey or lupin significantly blunted the postprandial increase in blood glucose
      concentrations compared to the reference meal (p < 0.001). In the overall
      statistical analysis, this effect was comparable for whey and lupin [Delta AUC
      whey-lupin = 8%, 0-60 min area under the curve (0-60 min AUC), p = 0.937], with a
      blunting effect of -46% by whey (p = 0.005, 0-60 min AUC) and of -54% by lupin (p
      < 0.001, 0-60 min AUC). When comparing whey and lupin data only, the insulin
      increase was found to be more pronounced for whey protein than for lupin
      supplementation (Delta AUC whey-lupin = 39%, 0-60 min AUC, p = 0.022). However,
      when comparing the insulin response of each supplementation to the one of the
      reference meal, no differences could be detected (whey p = 0.259, 0-60 min AUC;
      lupin p = 0.275, 0-60 min AUC). Conclusions: Results suggest that lupin and whey
      can both lower the increase of postprandial blood glucose concentrations to a
      comparable extent, implying the usability of lupin to reduce postprandial
      glycaemia. However, the insulin response following the supplementations to a
      carbohydrate-rich meal seems to differ for these two protein sources.

PMID- 28443027
TI  - Personalized Medication Response Prediction for Attention-Deficit Hyperactivity
      Disorder: Learning in the Model Space vs. Learning in the Data Space.
AB  - Attention-Deficit Hyperactive Disorder (ADHD) is one of the most common mental
      health disorders amongst school-aged children with an estimated prevalence of 5%
      in the global population (American Psychiatric Association, 2013). Stimulants,
      particularly methylphenidate (MPH), are the first-line option in the treatment of
      ADHD (Reeves and Schweitzer, 2004; Dopheide and Pliszka, 2009) and are prescribed
      to an increasing number of children and adolescents in the US and the UK every
      year (Safer et al., 1996; McCarthy et al., 2009), though recent studies suggest
      that this is tailing off, e.g., Holden et al. (2013). Around 70% of children
      demonstrate a clinically significant treatment response to stimulant medication
      (Spencer et al., 1996; Schachter et al., 2001; Swanson et al., 2001; Barbaresi et
      al., 2006). However, it is unclear which patient characteristics may moderate
      treatment effectiveness. As such, most existing research has focused on
      investigating univariate or multivariate correlations between a set of patient
      characteristics and the treatment outcome, with respect to dosage of one or
      several types of medication. The results of such studies are often contradictory
      and inconclusive due to a combination of small sample sizes, low-quality data, or
      a lack of available information on covariates. In this paper, feature extraction
      techniques such as latent trait analysis were applied to reduce the dimension of
      on a large dataset of patient characteristics, including the responses to symptom
      based questionnaires, developmental health factors, demographic variables such as
      age and gender, and socioeconomic factors such as parental income. We introduce a
      Bayesian modeling approach in a "learning in the model space" framework that
      combines existing knowledge in the literature on factors that may potentially
      affect treatment response, with constraints imposed by a treatment response
      model. The model is personalized such that the variability among subjects is
      accounted for by a set of subject-specific parameters. For remission
      classification, this approach compares favorably with conventional methods such
      as support vector machines and mixed effect models on a range of performance
      measures. For instance, the proposed approach achieved an area under receiver
      operator characteristic curve of 82-84%, compared to 75-77% obtained from
      conventional regression or machine learning ("learning in the data space")
      methods.

PMID- 28443028
TI  - Improved Model of Proton Pump Crystal Structure Obtained by Interactive Molecular
      Dynamics Flexible Fitting Expands the Mechanistic Model for Proton Translocation
      in P-Type ATPases.
AB  - The plasma membrane H+-ATPase is a proton pump of the P-type ATPase family and
      essential in plants and fungi. It extrudes protons to regulate pH and maintains a
      strong proton-motive force that energizes e.g., secondary uptake of nutrients.
      The only crystal structure of a H+-ATPase (AHA2 from Arabidopsis thaliana) was
      reported in 2007. Here, we present an improved atomic model of AHA2, obtained by
      a combination of model rebuilding through interactive molecular dynamics flexible
      fitting (iMDFF) and structural refinement based on the original data, but using
      up-to-date refinement methods. More detailed map features prompted local
      corrections of the transmembrane domain, in particular rearrangement of
      transmembrane helices 7 and 8, and the cytoplasmic N- and P-domains, and the new
      model shows improved overall quality and reliability scores. The AHA2 structure
      shows similarity to the Ca2+-ATPase E1 state, and provides a valuable starting
      point model for structural and functional analysis of proton transport mechanism
      of P-type H+-ATPases. Specifically, Asp684 protonation associated with
      phosphorylation and occlusion of the E1P state may result from hydrogen bond
      interaction with Asn106. A subsequent deprotonation associated with extracellular
      release in the E2P state may result from an internal salt bridge formation to an
      Arg655 residue, which in the present E1 state is stabilized in a solvated pocket.
      A release mechanism based on an in-built counter-cation was also later proposed
      for Zn2+-ATPase, for which structures have been determined in Zn2+ released E2P
      like states with the salt bridge interaction formed.

PMID- 28443029
TI  - Superior Effects of Eccentric to Concentric Knee Extensor Resistance Training on
      Physical Fitness, Insulin Sensitivity and Lipid Profiles of Elderly Men.
AB  - It has been reported that eccentric training of knee extensors is effective for
      improving blood insulin sensitivity and lipid profiles to a greater extent than
      concentric training in young women. However, it is not known whether this is also
      the case for elderly individuals. Thus, the present study tested the hypothesis
      that eccentric training of the knee extensors would improve physical function and
      health parameters (e.g., blood lipid profiles) of older adults better than
      concentric training. Healthy elderly men (60-76 years) were assigned to either
      eccentric training or concentric training group (n = 13/group), and performed 30
      60 eccentric or concentric contractions of knee extensors once a week. The
      intensity was progressively increased over 12 weeks from 10 to 100% of maximal
      concentric strength for eccentric training and from 50 to 100% for concentric
      training. Outcome measures were taken before and 4 days after the training
      period. The results showed that no sings of muscle damage were observed after any
      sessions. Functional physical fitness (e.g., 30-s chair stand) and maximal
      concentric contraction strength of the knee extensors increased greater (P <=
      0.05) after eccentric training than concentric training. Homeostasis model
      assessment, oral glucose tolerance test and whole blood glycosylated hemoglobin
      showed improvement of insulin sensitivity only after eccentric training (P <=
      0.05). Greater (P <= 0.05) decreases in fasting triacylglycerols, total, and low
      density lipoprotein cholesterols were evident after eccentric training than
      concentric training, and high-density lipoprotein cholesterols increased only
      after eccentric training. These results support the hypothesis and suggest that
      it is better to focus on eccentric contractions in exercise medicine.

PMID- 28443031
TI  - The High Calcium, High Phosphorus Rescue Diet Is Not Suitable to Prevent
      Secondary Hyperparathyroidism in Vitamin D Receptor Deficient Mice.
AB  - The vitamin D receptor (VDR) knockout (KO) mouse is a common model to unravel
      novel metabolic functions of vitamin D. It is recommended to feed these mice a
      high calcium (2%), high phosphorus (1.25%) diet, termed rescue diet (RD) to
      prevent hypocalcaemia and secondary hyperparathyroidism. First, we characterized
      the individual response of VDR KO mice to feeding a RD and found that the RD was
      not capable of normalizing the parathyroid hormone (PTH) concentrations in each
      VDR KO mouse. In a second study, we aimed to study whether RD with additional 1
      and 2% calcium (in total 3 and 4% of the diet) is able to prevent secondary
      hyperparathyroidism in the VDR KO mice. Wild type (WT) mice and VDR KO mice that
      received a normal calcium and phosphorus diet (ND) served as controls. Data
      demonstrated that the RD was no more efficient than the ND in normalizing PTH
      levels. An excessive dietary calcium concentration of 4% was required to reduce
      serum PTH concentrations in the VDR KO mice to PTH levels measured in WT mice.
      This diet, however, resulted in higher concentrations of circulating intact
      fibroblast growth factor 23 (iFGF23). To conclude, the commonly used RD is not
      suitable to normalize the serum PTH in VDR KO mice. Extremely high dietary
      calcium concentrations are necessary to prevent secondary hyperthyroidism in
      these mice, with the consequence that iFGF23 concentrations are being raised.
      Considering that PTH and iFGF23 exert numerous VDR independent effects, data
      obtained from VDR KO mice cannot be attributed solely to vitamin D.

PMID- 28443032
TI  - Fatty Acid Binding Protein 11a Is Required for Brain Vessel Integrity in
      Zebrafish.
AB  - The monolayer of endothelial cells (ECs) lining the intima of all blood vessel
      wall forms a semipermeable barrier that regulates tissue-fluid homeostasis,
      transport of nutrients, and migration of blood cells across the barrier. A number
      of signaling pathways and molecules mediate endothelial permeability, which plays
      important roles in a variety of the physiological and pathological conditions.
      Fatty acid binding proteins (FABPs) are able to bind various hydrophobic
      molecules, such as long-chain fatty acids, prostaglandins and eicosanoids. FABP4,
      a member of the family of FABPs, plays an important role in maintenance of
      glucose and lipid homeostasis as well as angiogenesis. In the present study, we
      found that fabp11a, the ortholog of mammalian FABP4, was highly expressed in
      developing brain vessels of zebrafish. Knockout of fabp11a gene caused hemorrhage
      in zebrafish brain. Morpholino mediated fabp11a gene knockdown phenocopied the
      hemorrhage in mutants. Furthermore, we demonstrated permeability of brain vessels
      in fabp11a mutant is significantly higher than that of control. In addition, COX
      and LOX inhibition partially rescued the brain vessel integrity defects caused by
      fabp11a loss-of-function, suggesting the integrity defect was relevant to the
      Fatty Acid function.

PMID- 28443030
TI  - Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of
      Diabetic Nephropathy.
AB  - The underlying mechanisms in the development of diabetic nephropathy are
      currently unclear and likely consist of a series of dynamic events from the early
      to late stages of the disease. Diabetic nephropathy is currently without curative
      treatments and it is acknowledged that even the earliest clinical manifestation
      of nephropathy is preceded by an established morphological renal injury that is
      in turn preceded by functional and metabolic alterations. An early manifestation
      of the diabetic kidney is the development of kidney hypoxia that has been
      acknowledged as a common pathway to nephropathy. There have been reports of
      altered mitochondrial function in the diabetic kidney such as altered mitophagy,
      mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia
      inducible factors and AMP-kinase. These factors are also likely to be intertwined
      in a complex manner. In this review, we discuss how these pathways are connected
      to mitochondrial production of reactive oxygen species (ROS) and how they may
      relate to the development of kidney hypoxia in diabetic nephropathy. From
      available literature, it is evident that early correction and/or prevention of
      mitochondrial dysfunction may be pivotal in the prevention and treatment of
      diabetic nephropathy.

PMID- 28443033
TI  - High Gama-Aminobutyric Acid Contents Involved in Abamectin Resistance and
      Predation, an Interesting Phenomenon in Spider Mites.
AB  - Abamectin has been widely used as an insecticide/acaricide for more than 30 years
      because of its superior bioactivity. Recently, an interesting phenomenon was
      identified in the carmine spider mite, Tetranychus cinnabarinus, an important
      pest in agriculture. The gamma aminobutyric acid (GABA) contents in a laboratory
      abamectin resistant strain of T. cinnabarinus (AbR) were significantly increased.
      Decreases in activity and mRNA expression of GABA transaminase (GABA-T) were
      responsible for GABA accumulation in AbR mites. To clarify the mechanism of GABA
      accumulation mediated abamectin resistance, three artificial approaches were
      conducted to increase GABA contents in susceptible mites, including feeding of
      vigabatrin (a specific inhibitor of GABA-T), feeding of exogenous GABA, and
      inhibition of GABA-T gene expression. The results showed that susceptible mites
      developed resistance to abamectin when the GABA contents were artificially
      increased. We also observed that the mites with higher GABA contents moved more
      slowly, which is consistent with the fact that GABA is an inhibitory
      neurotransmitter in arthropods. Subsequently, functional response assays revealed
      that predation rates of predatory mites on GABA accumulated abamectin-resistant
      mites were much higher than control groups. The tolerance to abamectin, slow
      crawling speed, and vulnerability to predators were all resulted from GABA
      accumulation. This relationship between GABA and predation was also confirmed in
      a field-collected population. Our finding indicates that predatory mites might be
      used as a tool for biological control to circumvent the development of abamectin
      resistance in mites.

PMID- 28443034
TI  - Effectiveness of Alcohol, Smoking, and Substance Involvement Screening Test
      Linked Brief Intervention on Harmful and Hazardous Alcohol Use in Nigerian
      Semirural Communities: A Non-Randomized Intervention Study.
AB  - OBJECTIVE: To determine the prevalence of alcohol consumption and the
      effectiveness of the alcohol, smoking, and substance involvement screening test
      (ASSIST)-linked brief intervention on hazardous and harmful alcohol use in
      semirural settings in Nigeria. METHODS: In this single arm non-randomized
      intervention study delivered by community health extension workers (CHEW),
      participants (N = 1,203), 15 years and older, recruited between October 2010 and
      April 2011 were assessed for prevalence of alcohol consumption and the associated
      level of risk. Scores of 0-10 were classified as lower risk scores, 11-26 as
      moderate risk, and 27+ as high risk. This was followed by a brief intervention.
      Prevalence of alcohol consumption and level of risk was assessed at 3 and 6
      months postbrief intervention. Main outcome measure was the change in ASSIST
      scores at 3 and 6 months postintervention. RESULTS: There was a statistically
      significant difference in the prevalence of alcohol use at baseline compared with
      that at 6 months, chi2(2) = 4.2, p = 0.01. Among all respondents, a repeated
      measures ANOVA with a Greenhouse-Geisser correction showed that mean ASSIST score
      significantly reduced between time points [F(1.541, 34.092) = 53.241, p < 0.001].
      Post hoc tests using the Bonferroni correction revealed that this difference was
      due to a significant reduction in the mean ASSIST scores at 3 months vs.
      baseline, p = 0.001, but not at 3 vs. 6 months, p = 0.09. CONCLUSION: There is a
      potential for CHEW-administered ASSIST-linked screening, brief intervention, and
      referral to treatment for unhealthy alcohol use in Nigerian semirural
      communities. This is feasible considering serious dearth of addiction specialists
      in the country.

PMID- 28443035
TI  - Next Speakers Plan Their Turn Early and Speak after Turn-Final "Go-Signals".
AB  - In conversation, turn-taking is usually fluid, with next speakers taking their
      turn right after the end of the previous turn. Most, but not all, previous
      studies show that next speakers start to plan their turn early, if possible
      already during the incoming turn. The present study makes use of the list
      completion paradigm (Barthel et al., 2016), analyzing speech onset latencies and
      eye-movements of participants in a task-oriented dialogue with a confederate. The
      measures are used to disentangle the contributions to the timing of turn-taking
      of early planning of content on the one hand and initiation of articulation as a
      reaction to the upcoming turn-end on the other hand. Participants named objects
      visible on their computer screen in response to utterances that did, or did not,
      contain lexical and prosodic cues to the end of the incoming turn. In the
      presence of an early lexical cue, participants showed earlier gaze shifts toward
      the target objects and responded faster than in its absence, whereas the presence
      of a late intonational cue only led to faster response times and did not affect
      the timing of participants' eye movements. The results show that with a
      combination of eye-movement and turn-transition time measures it is possible to
      tease apart the effects of early planning and response initiation on turn timing.
      They are consistent with models of turn-taking that assume that next speakers (a)
      start planning their response as soon as the incoming turn's message can be
      understood and (b) monitor the incoming turn for cues to turn-completion so as to
      initiate their response when turn-transition becomes relevant.

PMID- 28443037
TI  - Analyzing Dyadic Sequence Data-Research Questions and Implied Statistical Models.
AB  - The analysis of observational data is often seen as a key approach to
      understanding dynamics in romantic relationships but also in dyadic systems in
      general. Statistical models for the analysis of dyadic observational data are not
      commonly known or applied. In this contribution, selected approaches to dyadic
      sequence data will be presented with a focus on models that can be applied when
      sample sizes are of medium size (N = 100 couples or less). Each of the
      statistical models is motivated by an underlying potential research question, the
      most important model results are presented and linked to the research question.
      The following research questions and models are compared with respect to their
      applicability using a hands on approach: (I) Is there an association between a
      particular behavior by one and the reaction by the other partner? (Pearson
      Correlation); (II) Does the behavior of one member trigger an immediate reaction
      by the other? (aggregated logit models; multi-level approach; basic Markov
      model); (III) Is there an underlying dyadic process, which might account for the
      observed behavior? (hidden Markov model); and (IV) Are there latent groups of
      dyads, which might account for observing different reaction patterns? (mixture
      Markov; optimal matching). Finally, recommendations for researchers to choose
      among the different models, issues of data handling, and advises to apply the
      statistical models in empirical research properly are given (e.g., in a new r
      package "DySeq").

PMID- 28443036
TI  - Auditory-Motor Rhythms and Speech Processing in French and German Listeners.
AB  - Moving to a speech rhythm can enhance verbal processing in the listener by
      increasing temporal expectancies (Falk and Dalla Bella, 2016). Here we tested
      whether this hypothesis holds for prosodically diverse languages such as German
      (a lexical stress-language) and French (a non-stress language). Moreover, we
      examined the relation between motor performance and the benefits for verbal
      processing as a function of language. Sixty-four participants, 32 German and 32
      French native speakers detected subtle word changes in accented positions in
      metrically structured sentences to which they previously tapped with their index
      finger. Before each sentence, they were cued by a metronome to tap either
      congruently (i.e., to accented syllables) or incongruently (i.e., to non-accented
      parts) to the following speech stimulus. Both French and German speakers detected
      words better when cued to tap congruently compared to incongruent tapping.
      Detection performance was predicted by participants' motor performance in the non
      verbal cueing phase. Moreover, tapping rate while participants tapped to speech
      predicted detection differently for the two language groups, in particular in the
      incongruent tapping condition. We discuss our findings in light of the rhythmic
      differences of both languages and with respect to recent theories of expectancy
      driven and multisensory speech processing.

PMID- 28443038
TI  - Mother-Infant and Extra-Dyadic Interactions with a New Social Partner:
      Developmental Trajectories of Early Social Abilities during Play.
AB  - Mother-infant interactions during feeding and play are pivotal experiences in the
      development of infants' early social abilities (Stern, 1985, 1995; Biringen,
      2000). Stern indicated distinctive characteristics of mother-infant interactions,
      respectively, during feeding and play, suggesting to evaluate both to better
      describe the complexity of such early affective and social experiences (Stern,
      1996). Moreover, during the first years of life, infants acquire cognitive and
      social skills that allow them to interact with new social partners in extra
      dyadic interactions. However, the relations between mother-child interactions and
      infants' social skills in extra-dyadic interactions are still unknown. We
      investigated longitudinally the relations between mother-child interactions
      during feeding and play and child's pre-verbal communicative abilities in extra
      dyadic interactions during play. 20 dyads were evaluated at T1 (infants aged
      between 9-22 months) and 6 months later, at T2. The interdyadic differences in
      mother-infant interactions during feeding and play were evaluated, respectively,
      with the "Feeding Scale" (Chatoor et al., 1997) and with the "Play Scale"
      (Chatoor, 2006) and the socio-communicative abilities of children with a new
      social partner during play were evaluated with the "Early Social Communication
      Scales" (Mundy et al., 2003). We distinguished the dyads into two categories:
      dyads with functional interactions (high dyadic reciprocity, low dyadic conflict)
      and dyads with dysfunctional interactions (lower dyadic reciprocity, higher
      dyadic conflict). At T1, infants belonging to dyads with dysfunctional
      interactions were significantly lower in "Initiating Joint Attention" and in
      "Responding to Joint Attention" in interaction with a new social partner compared
      to the infants belonging to dyads with functional interactions. At T2, infants
      belonging to dyads with dysfunctional interactions were significantly lower in
      "Initiating Social Interactions" with a new social partner compared to the
      infants belonging to dyads with functional interactions. There were significant
      correlations between the quality of mother-infant interactions during feeding and
      infants' social abilities in interaction with a stranger both at T1 and at T2.
      This study showed a stable relation over time between mother-child interactions
      and child's social communicative skills in extra-dyadic interactions.

PMID- 28443039
TI  - Primary Emotional Systems and Personality: An Evolutionary Perspective.
AB  - The present article highlights important concepts of personality including
      stability issues from the perspective of situational demands and stability over
      the life-course. Following this more introductory section, we argue why
      individual differences in primary emotional systems may represent the
      phylogenetically oldest parts of human personality. Our argumentation leads to
      the need to increasingly consider individual differences in the raw
      affects/emotions of people to understand human personality in a bottom-up
      fashion, which can be coordinated with top-down perspectives. In support of this
      idea, we also review existing evidence linking individual differences in primal
      emotions as assessed with the Affective Neuroscience Personality Scales and the
      widely accepted Big Five Model of Personality. In this context, we provide
      additional evidence on the link between primal emotions and personality in German
      and Chinese sample populations. In short, this article addresses evolutionary
      perspectives in the evaluation of human personality, highlighting some of the
      ancestral emotional urges that probably still control variations in the
      construction of human personality structures. Moreover, we address how individual
      differences in primary emotional systems can illuminate linkages to major human
      psychopathologies and the potential advantages and disadvantages of carrying a
      certain personality trait within certain cultural/environmental niches.

PMID- 28443041
TI  - National Identification Counteracts the Sedative Effect of Positive Intergroup
      Contact on Ethnic Activism.
AB  - Positive intergroup contact with socially and economically advantaged national
      majorities has been shown to reduce ethnic identification among minorities,
      thereby undermining ethnic minority activism. This finding implies that ethnic
      identity is the relevant social identity driving ethnic minorities' struggle for
      equality. We argue that the study of the "sedating" effect of positive intergroup
      contact for minorities should be more nuanced. The existence of multiple and
      sometimes interplaying social identities can foster a reinterpretation of the
      meaning of "ethnic" activism. This study therefore examines how the interplay of
      ethnic and national identities shapes the sedating effect of contact on minority
      activism. We expect national identification to buffer the sedated activism
      resulting from reduced ethnic identification. That is, the mediation from
      intergroup contact to reduced ethnic activism through weakened ethnic
      identification is expected to be moderated by national identification. With
      survey data from Bulgaria, we investigated support for ethnic activism among
      Bulgarian Roma (N = 320) as a function of their contact with the national
      majority as well as their degree of ethnic and national identification. The
      predicted moderated mediation was revealed: a negative indirect relationship
      between contact and activism through decreased ethnic identification occurred
      among Roma with low national identification, whereas no sedating effect occurred
      among Roma identifying strongly as members of the Bulgarian nation. We discuss
      the meaning of national identification for the Roma minority, who experience
      harsh discrimination in countries where they have been historically settled, as
      well as convergence of these findings with work on dual identification. We
      highlight the role of interacting social identities in mobilizing resources for
      activism and the importance of adopting a critical view on ethnic discourse when
      studying activism in both traditional and immigrant minorities.

PMID- 28443042
TI  - Editorial: Psychology and Policy.

PMID- 28443040
TI  - The Impact of Early Visual Deprivation on Spatial Hearing: A Comparison between
      Totally and Partially Visually Deprived Children.
AB  - The specific role of early visual deprivation on spatial hearing is still
      unclear, mainly due to the difficulty of comparing similar spatial skills at
      different ages and to the difficulty in recruiting young blind children from
      birth. In this study, the effects of early visual deprivation on the development
      of auditory spatial localization have been assessed in a group of seven 3-5 years
      old children with congenital blindness (n = 2; light perception or no perception
      of light) or low vision (n = 5; visual acuity range 1.1-1.7 LogMAR), with the
      main aim to understand if visual experience is fundamental to the development of
      specific spatial skills. Our study led to three main findings: firstly, totally
      blind children performed overall more poorly compared sighted and low vision
      children in all the spatial tasks performed; secondly, low vision children
      performed equally or better than sighted children in the same auditory spatial
      tasks; thirdly, higher residual levels of visual acuity are positively correlated
      with better spatial performance in the dynamic condition of the auditory
      localization task indicating that the more residual vision the better spatial
      performance. These results suggest that early visual experience has an important
      role in the development of spatial cognition, even when the visual input during
      the critical period of visual calibration is partially degraded like in the case
      of low vision children. Overall these results shed light on the importance of
      early assessment of spatial impairments in visually impaired children and early
      intervention to prevent the risk of isolation and social exclusion.

PMID- 28443043
TI  - Leniency Bias in Performance Ratings: The Big-Five Correlates.
AB  - Some researchers assume that employees' personality characteristics affect
      leniency in rating others and themselves. However, little research has
      investigated these two tendencies at the same time. In the present study we
      developed one index for other-rating leniency and another one for self-rating
      leniency. Based on a review of the literature, we hypothesized that a generous
      assessment of peers would more likely be made by those who are extroverted and
      agreeable than by those who are not. Furthermore, a generous assessment of
      oneself would more likely be made by people who are conscientious and emotionally
      stable, than by people who are not. We also investigated if the leniency in
      rating others and the leniency in rating oneself are part of a more general
      leniency tendency. Data collected from a sample of real estate dealers provided
      support for the above hypotheses. Limitations and implications for future
      research are discussed.

PMID- 28443044
TI  - Are Psychology Journals Anti-replication? A Snapshot of Editorial Practices.
AB  - Recent research in psychology has highlighted a number of replication problems in
      the discipline, with publication bias - the preference for publishing original
      and positive results, and a resistance to publishing negative results and
      replications- identified as one reason for replication failure. However, little
      empirical research exists to demonstrate that journals explicitly refuse to
      publish replications. We reviewed the instructions to authors and the published
      aims of 1151 psychology journals and examined whether they indicated that
      replications were permitted and accepted. We also examined whether journal
      practices differed across branches of the discipline, and whether editorial
      practices differed between low and high impact journals. Thirty three journals
      (3%) stated in their aims or instructions to authors that they accepted
      replications. There was no difference between high and low impact journals. The
      implications of these findings for psychology are discussed.

PMID- 28443045
TI  - Automatic Approach Tendencies toward High and Low Caloric Food in Restrained
      Eaters: Influence of Task-Relevance and Mood.
AB  - Objective: Although restrained eaters are motivated to control their weight by
      dieting, they are often unsuccessful in these attempts. Dual process models
      emphasize the importance of differentiating between controlled and automatic
      tendencies to approach food. This study investigated the hypothesis that
      heightened automatic approach tendencies in restrained eaters would be especially
      prominent in contexts where food is irrelevant for their current tasks.
      Additionally, we examined the influence of mood on the automatic tendency to
      approach food as a function of dietary restraint. Methods: An Affective Simon
      Task-manikin was administered to measure automatic approach tendencies where food
      is task-irrelevant, and a Stimulus Response Compatibility task (SRC) to measure
      automatic approach in contexts where food is task-relevant, in 92 female
      participants varying in dietary restraint. Prior to the task, sad, stressed,
      neutral, or positive mood was induced. Food intake was measured during a bogus
      taste task after the computer tasks. Results: Consistent with their diet goals,
      participants with a strong tendency to restrain their food intake showed a
      relatively weak approach bias toward food when food was task-relevant (SRC) and
      this effect was independent of mood. Restrained eaters showed a relatively strong
      approach bias toward food when food was task-irrelevant in the positive condition
      and a relatively weak approach in the sad mood. Conclusion: The weak approach
      bias in contexts where food is task-relevant may help high-restrained eaters to
      comply with their diet goal. However, the strong approach bias in contexts where
      food is task-irrelevant and when being in a positive mood may interfere with
      restrained eaters' goal of restricting food-intake.

PMID- 28443046
TI  - Craving Behavior Intervention in Ameliorating College Students' Internet Game
      Disorder: A Longitudinal Study.
AB  - Craving, as a central feature of addiction and a precursor of relapse, is
      targeted recently in addiction intervention. While Internet gaming disorder
      (IGD), conceptualized as a behavioral addiction, is lack of effective treatment
      practice and exploration of its mechanism. This research aims to test the
      effectiveness and detect the active ingredients of craving behavior intervention
      (CBI) in mitigation of IGD among young adults. A total of 63 male college
      students with IGD were assigned into the intervention group (six-session CBI
      intervention) or the waiting-list control group. Structured questionnaires were
      administered at pre-intervention (T1), post-intervention (T2), 3-month follow-up
      (T3), and 6-month follow-up (T4). Compared to the control group, a significant
      decrease in the severity of IGD in intervention group was found at post
      intervention and lasting to 6 months after intervention. The value changes of
      craving could partially mediate the relationship between intervention and changes
      of IGD among all effects tests (immediate, T2-T1; short-term, T3-T1; and long
      term effects, T4-T1). Further, explorations of the active ingredients of
      intervention found depression relief and shift of psychological needs from
      Internet to real life significantly predict craving amelioration at both post
      intervention and 6-month follow-up. Although preliminary, the current study
      provides evidence for the value of craving-aimed intervention practice in IGD
      treatment and identifies two potential active ingredients for mitigation of
      craving, and the long-term therapeutic benefits are further conferred. Registry
      name: The behavioral and brain mechanism of IGD; URL:
      https://www.clinicaltrials.gov/ct2/show/NCT02550405; Registration number:
      NCT02550405.

PMID- 28443047
TI  - Synchrony in Joint Action Is Directed by Each Participant's Motor Control System.
AB  - In this work, we ask how the probability of achieving synchrony in joint action
      is affected by the choice of motion parameters of each individual. We use the
      mirror game paradigm to study how changes in leader's motion parameters,
      specifically frequency and peak velocity, affect the probability of entering the
      state of co-confidence (CC) motion: a dyadic state of synchronized, smooth and co
      predictive motions. In order to systematically study this question, we used a one
      person version of the mirror game, where the participant mirrored piece-wise
      rhythmic movements produced by a computer on a graphics tablet. We systematically
      varied the frequency and peak velocity of the movements to determine how these
      parameters affect the likelihood of synchronized joint action. To assess
      synchrony in the mirror game we used the previously developed marker of co
      confident (CC) motions: smooth, jitter-less and synchronized motions indicative
      of co-predicative control. We found that when mirroring movements with low
      frequencies (i.e., long duration movements), the participants never showed CC,
      and as the frequency of the stimuli increased, the probability of observing CC
      also increased. This finding is discussed in the framework of motor control
      studies showing an upper limit on the duration of smooth motion. We confirmed the
      relationship between motion parameters and the probability to perform CC with
      three sets of data of open-ended two-player mirror games. These findings
      demonstrate that when performing movements together, there are optimal movement
      frequencies to use in order to maximize the possibility of entering a state of
      synchronized joint action. It also shows that the ability to perform synchronized
      joint action is constrained by the properties of our motor control systems.

PMID- 28443048
TI  - The Contribution of Phonological Awareness to Reading Fluency and Its Individual
      Sub-skills in Readers Aged 9- to 12-years.
AB  - Research examining phonological awareness (PA) contributions to reading in
      established readers of different skill levels is limited. The current study
      examined the contribution of PA to phonological decoding, visual word
      recognition, reading rate, and reading comprehension in 124 fourth to sixth grade
      children (aged 9-12 years). On the basis of scores on the FastaReada measure of
      reading fluency participants were allocated to one of three reading ability
      categories: dysfluent (n = 47), moderate (n = 38) and fluent (n = 39). For the
      dysfluent group, PA contributed significantly to all reading measures except
      rate, but in the moderate group only to phonological decoding. PA did not
      influence performances on any of the reading measures examined for the fluent
      reader group. The results support the notion that fluency is characterized by a
      shift from conscious decoding to rapid and accurate visual recognition of words.
      Although PA may be influential in reading development, the results of the current
      study show that it is not sufficient for fluent reading.

PMID- 28443049
TI  - Parental Factors Associated with Rumination Related Metacognitive Beliefs in
      Adolescence.
AB  - An increasing number of research studies have suggested that metacognition is
      associated with individuals' mental health. Specifically, metacognitive beliefs
      about rumination was proposed to link to the onset and maintenance of depression
      according to the metacognitive model of depression. The current study aimed to
      serve as a pilot study exploring how parents' metacognitive beliefs and parenting
      characteristics are associated with rumination related metacognitive beliefs in
      adolescents. Eighty-five parent-youth dyads were invited to complete a set of
      questionnaires examining their metacognitive beliefs about rumination followed by
      a difficult puzzle task, in which parent-adolescent interaction patterns were
      recorded to examine the parenting style. Results found that parents' and
      adolescents' positive metacognitive beliefs about rumination were significantly
      associated with each other. In addition, parental negativity was significantly
      associated with adolescents' positive metacognitive beliefs of rumination and
      parental over-involvement was marginally associated with adolescents' negative
      metacognitive beliefs of rumination. The findings highlighted the association
      between parental factors and adolescents' metacognitive beliefs about rumination.
      Implications on the prevention of adolescent's depression were discussed.

PMID- 28443050
TI  - Response: Commentary: Effects of Age and Initial Risk Perception on Balloon
      Analog Risk Task: The Mediating Role of Processing Speed and Need for Cognitive
      Closure.

PMID- 28443052
TI  - Gih (Qi): Beyond Affordance.
AB  - Ancient Eastern thought posited the ontological integration of the "mind-body
      world". The body-mind syncretism was a foundational precept in Eastern philosophy
      in which "Gih" ("Qi") was considered the basic entity of the universe and the
      human being. This study attempts to build a meta-theory and to demonstrate
      empirical designs for Gih, discussing the problems of the mind and body, or the
      subject and object, compared with the concept of "affordance" proposed by
      ecological approaches. The notion of Gih extends beyond that of affordance in
      that Gih activates a psychosomatic process between the physical condition and the
      mental state that facilitates the bi-directional interactions between subject and
      object. Therefore, the concept of Gih integrates mind and body, providing a means
      of comparing Eastern and Western philosophical systems.

PMID- 28443051
TI  - Social Behavior of Pet Dogs Is Associated with Peripheral OXTR Methylation.
AB  - Oxytocin is a key modulator of emotional processing and social cognitive
      function. In line with this, polymorphisms of genes involved in oxytocin
      signaling, like the oxytocin receptor (OXTR) gene, are known to influence social
      behavior in various species. However, to date, no study has investigated
      environmental factors possibly influencing the epigenetic variation of the OXTR
      gene and its behavioral effects in dogs. Pet dogs form individualized and strong
      relationships with their owners who are central figures in the social environment
      of their dogs and therefore might influence the methylation levels of their OXTR
      gene. Here we set out to investigate whether DNA methylation within the OXTR
      promoter region of pet dogs is linked to their owner's interaction style and to
      the social behavior of the dogs. To be able to do so, we collected buccal
      epithelial cells and, in Study 1, we used pyrosequencing techniques to look for
      differentially methylated CpG sites in the canine OXTR promoter region on a
      heterogeneous sample of dogs and wolves of different ages and keeping conditions.
      Four identified sites (at positions -727, -751, -1371, and -1383 from
      transcription start site) showing more than 10% methylation variation were then,
      in Study 2, measured in triplicate in 217 pet Border Collies previously tested
      for reactions to an adverse social situation (i.e., approach by a threatening
      human) and with available data on their owners' interaction styles. We found that
      CpG methylation was significantly associated with the behavior of the dogs, in
      particular with the likelihood that dogs would hide behind their owner or remain
      passive when approached by a threatening human. On the other hand, CpG
      methylation was not related to the owners' behavior but to dog sex (at position 
      1371). Our findings underpin the complex relationship between epigenetics and
      behavior and highlight the importance of including epigenetic methods in the
      analysis of dog behavioral development. Further research is needed to investigate
      which environmental factors influence the epigenetic variation of the OXTR gene.

PMID- 28443053
TI  - Perceptual Improvement of Lexical Tones in Infants: Effects of Tone Language
      Experience.
AB  - To learn words in a tonal language, tone-language learners should not only
      develop better abilities for perceiving consonants and vowels, but also for
      lexical tones. The divergent trend of enhancing sensitivity to native phonetic
      contrasts and reduced sensitivity to non-native phonetic contrast is
      theoretically essential to evaluate effects of listening to an ambient language
      on speech perception development. The loss of sensitivity in discriminating
      lexical tones among non-tonal language-learning infants was apparent between 6
      and 12 months of age, but only few studies examined trends of differentiating
      native lexical tones in infancy. The sensitivity in discriminating lexical tones
      among 6-8 and 10-12 month-old Mandarin-learning infants (n = 120) was tested in
      Experiment 1 using three lexical tone contrasts of Mandarin. Facilitation of
      linguistic experience was shown in the tonal contrast (Tone 1 vs. 3), but both
      age groups performed similar in the other two tonal contrasts (Tone 2 vs. 4; Tone
      2 vs. 3). In Experiment 2, 6-8 and 10-12 month-old Mandarin-learning infants (n =
      90) were tested with tonal contrasts that have pitch contours either similar to
      or inverse from lexical tones in Mandarin, and perceptual improvement was shown
      only in a tonal contrast with familiar pitch contours (i.e., Tone 1 vs. 3). In
      Experiment 3, 6-8 and 10-12 month-old English-learning infants (n = 40) were
      tested with Tone 1 vs. 3 contrast of Mandarin and showed an improvement in the
      perception of non-native lexical tones. This study reveals that tone-language
      learning infants develop more accurate representations of lexical tones around
      their first birthday, and the results of both tone and non-tone language-learning
      infants imply that the rate of development depends on listening experience and
      the acoustical salience of specific tone contrasts.

PMID- 28443055
TI  - Lacanian Concept of Desire in Analytic Clinic of Psychosis.

PMID- 28443054
TI  - Childbirth Induced Posttraumatic Stress Syndrome: A Systematic Review of
      Prevalence and Risk Factors.
AB  - Background: Posttraumatic stress related with the childbirth experience of full
      term delivery with health outcomes has been recently documented in a growing body
      of studies. The magnitude of this condition and the factors that might put a
      woman at risk for developing childbirth-related postpartum posttraumatic stress
      disorder (PP-PTSD) symptoms are not fully understood. Methods: In this systematic
      review of 36 articles representing quantitative studies of primarily community
      samples, we set to examine PP-PTSD prevalence rates and associated predictors
      with a focus on the role of prior PTSD and time since childbirth. Results: A
      significant minority of women endorsed PP-PTSD following successful birth. Acute
      PP-PTSD rates were between 4.6 and 6.3%, and endorsement of clinically
      significant PP-PTSD symptoms was identified in up to 16.8% of women in community
      samples of high quality studies. Negative subjective experience of childbirth
      emerged as the most important predictor. Endorsement of PTSD before childbirth
      contributed to PP-PTSD; nevertheless, women without PTSD also exhibited PP-PTSD,
      with acute rates at 4.6%, signifying a new PTSD onset in the postpartum period.
      Conclusion: Although the majority of women cope well, childbirth for some can be
      perceived as a highly stressful experience and even result in the development of
      PP-PTSD symptoms. More research is needed to understand postpartum adaption and
      childbirth-related posttraumatic stress outcomes.

PMID- 28443056
TI  - Concerns, Mental Health, and Quality of Life in Living Kidney Donation-Parent
      Donor Candidates Worry Less about Themselves.
AB  - Even though the majority of living kidney donor candidates appear in good mental
      health and show few concerns little is known concerning the influence of the type
      of donor-recipient relationship on donor candidates' specific concerns with
      regard to kidney donation. 136 donor candidates at Virgen del Rocio University
      Hospital of Seville filled in the Scale of Concerns Regarding Living Kidney
      Donation of whom 105 donor candidates and their corresponding recipients (105
      patients with End-Stage Renal Disease) were further evaluated with regard to
      mental health (Hospital Anxiety and Depression Scale, Beck Depression Inventory
      II) and quality of life (SF-36 Health Survey). As hypothesized recipients scored
      higher on depression and lower on quality of life. Donor candidates intending to
      donate to their children were significantly less concerned about risks of
      donation for themselves compared to donor candidates donating to siblings. Our
      findings highlight the importance of the type of donor-recipient relationship to
      understand specific concerns of donor candidates and optimize psychosocial
      assessment and support. From an evolutionary perspective parents lack of concern
      about their own well-being can be seen as an altruistic behavior to increase
      children's fitness at the (potential) expense of their own fitness.

PMID- 28443057
TI  - Cognitive-constructivist Approach in Medical Settings: The Use of Personal
      Meaning Questionnaire for Neurological Patients' Personality Investigation.
AB  - Objective: The cognitive-constructivist psychotherapy approach considers the self
      as a continuous regulation process between present and past experience, in which
      attributions of meaning is characterized by the use of internal rules. In this
      conception, everyone would be driven by a specific inner coherence called
      Personal Meaning Organization (PMO). Such approach has never been applied to
      neurological patients by means of ad hoc developed tools. We performed an
      explorative study aimed to characterize personality styles in different
      neurological conditions within the theoretical framework of cognitive
      constructivist model. Materials and Methods: Three groups of neurological
      patients (Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Primary Headache)
      and a sample of healthy participants, each composed by 15 participants, for a
      total of 60 participants, were recruited. The Personal Meaning Questionnaire
      (PMQ), an Italian questionnaire assessing PMOs construct, and other clinical
      tools for psychological and quality of life assessment were administered to all
      subjects. Results: The main finding concerned the detection, across all clinical
      conditions, of a higher prevalence of phobic personality style, with Amyotrophic
      Lateral Sclerosis showing a relevant prevalence of such PMO with respect to all
      other neurological conditions and controls. However, with respect to controls, in
      all clinical conditions, PMQ highlighted a tendency, even if not statistically
      significant, to codify experience by means of specific cognitive and emotional
      patterns. Conclusion: Our findings represent the first contribution towards
      understanding the personality profiles of patients affected by neurological
      conditions according to cognitive-constructivist theory.

PMID- 28443058
TI  - Predicting Outcome 12 Months after Mild Traumatic Brain Injury in Patients
      Admitted to a Neurosurgery Service.
AB  - OBJECTIVE: Accurate outcome prediction models for patients with mild traumatic
      brain injury (MTBI) are key for prognostic assessment and clinical decision
      making. Using multivariate machine learning, we tested the unique and added
      predictive value of (1) magnetic resonance imaging (MRI)-based brain morphometric
      and volumetric characterization at 4-week postinjury and (2) demographic,
      preinjury, injury-related, and postinjury variables on 12-month outcomes,
      including global functioning level, postconcussion symptoms, and mental health in
      patients with MTBI. METHODS: A prospective, cohort study of patients (n = 147)
      aged 16-65 years with a 12-month follow-up. T1-weighted 3 T MRI data were
      processed in FreeSurfer, yielding accurate cortical reconstructions for surface
      based analyses of cortical thickness, area, and volume, and brain segmentation
      for subcortical and global brain volumes. The 12-month outcome was defined as a
      composite score using a principal component analysis including the Glasgow
      Outcome Scale Extended, Rivermead Postconcussion Questionnaire, and Patient
      Health Questionnaire-9. Using leave-one-out cross-validation and permutation
      testing, we tested and compared three prediction models: (1) MRI model, (2)
      clinical model, and (3) MRI and clinical combined. RESULTS: We found a strong
      correlation between observed and predicted outcomes for the clinical model (r =
      0.55, p < 0.001). The MRI model performed at the chance level (r = 0.03, p =
      0.80) and the combined model (r = 0.45, p < 0.002) were slightly weaker than the
      clinical model. Univariate correlation analyses revealed the strongest
      association with outcome for postinjury factors of posttraumatic stress
      (Posttraumatic Symptom Scale-10, r = 0.61), psychological distress (Hospital
      Anxiety and Depression Scale, r = 0.52), and widespread pain (r = 0.43) assessed
      at 8 weeks. CONCLUSION: We found no added predictive value of MRI-based measures
      of brain cortical morphometry and subcortical volumes over and above demographic
      and clinical features.

PMID- 28443059
TI  - Algorithm for Turning Detection and Analysis Validated under Home-Like Conditions
      in Patients with Parkinson's Disease and Older Adults using a 6 Degree-of-Freedom
      Inertial Measurement Unit at the Lower Back.
AB  - INTRODUCTION: Aging and age-associated disorders such as Parkinson's disease (PD)
      are often associated with turning difficulties, which can lead to falls and
      fractures. Valid assessment of turning and turning deficits specifically in non
      standardized environments may foster specific treatment and prevention of
      consequences. METHODS: Relative orientation, obtained from 3D-accelerometer and
      3D-gyroscope data of a sensor worn at the lower back, was used to develop an
      algorithm for turning detection and qualitative analysis in PD patients and
      controls in non-standardized environments. The algorithm was validated with a
      total of 2,304 turns >=90 degrees  extracted from an independent dataset of 20 PD
      patients during medication ON- and OFF-conditions and 13 older adults. Video
      observation by two independent clinical observers served as gold standard.
      RESULTS: In PD patients under medication OFF, the algorithm detected turns with a
      sensitivity of 0.92, a specificity of 0.89, and an accuracy of 0.92. During
      medication ON, values were 0.92, 0.78, and 0.83. In older adults, the algorithm
      reached validation values of 0.94, 0.89, and 0.92. Turning magnitude (difference,
      0.06 degrees ; SEM, 0.14 degrees ) and duration (difference, 0.004 s; SEM, 0.005
      s) yielded high correlation values with gold standard. Overall accuracy for
      direction of turning was 0.995. Intra class correlation of the clinical observers
      was 0.92. CONCLUSION: This wearable sensor- and relative orientation-based
      algorithm yields very high agreement with clinical observation for the detection
      and evaluation of >=90 degrees  turns under non-standardized conditions in PD
      patients and older adults. It can be suggested for the assessment of turning in
      daily life.

PMID- 28443060
TI  - The Vestibular Implant: Hearing Preservation during Intralabyrinthine Electrode
      Insertion-A Case Report.
AB  - OBJECTIVE: The vestibular implant seems feasible as a clinically useful device in
      the near future. However, hearing preservation during intralabyrinthine
      implantation remains a challenge. It should be preserved to be able to treat
      patients with bilateral vestibulopathy and (partially) intact hearing. This case
      study investigated the feasibility of hearing preservation during the acute phase
      after electrode insertion in the semicircular canals. METHODS: A 40-year-old
      woman with normal hearing underwent a translabyrinthine approach for a vestibular
      schwannoma Koos Grade IV. Hearing was monitored using auditory brainstem response
      audiometry (ABR). ABR signals were recorded synchronously to video recordings of
      the surgery. Following the principles of soft surgery, a conventional dummy
      electrode was inserted in the lateral semicircular canal for several minutes and
      subsequently removed. The same procedure was then applied for the posterior
      canal. Finally, the labyrinthectomy was completed, and the schwannoma was
      removed. RESULTS: Surgery was performed without complications. No leakage of
      endolymph and no significant reduction of ABR response were observed during
      insertion and after removal of the electrodes from the semicircular canals,
      indicting no damage to the peripheral auditory function. The ABR response
      significantly changed when the semicircular canals were completely opened during
      the labyrinthectomy. This was indicated by a change in the morphology and latency
      of peak V of the ABR signal. CONCLUSION: Electrode insertion in the semicircular
      canals is possible without acutely damaging the peripheral auditory function
      measured with ABR, as shown in this proof-of-principle clinical investigation.

PMID- 28443061
TI  - A Linear Temporal Increase in Thrombin Activity and Loss of Its Receptor in Mouse
      Brain following Ischemic Stroke.
AB  - BACKGROUND: Brain thrombin activity is increased following acute ischemic stroke
      and may play a pathogenic role through the protease-activated receptor 1 (PAR1).
      In order to better assess these factors, we obtained a novel detailed temporal
      and spatial profile of thrombin activity in a mouse model of permanent middle
      cerebral artery occlusion (pMCAo). METHODS: Thrombin activity was measured by
      fluorescence spectroscopy on coronal slices taken from the ipsilateral and
      contralateral hemispheres 2, 5, and 24 h following pMCAo (n = 5, 6, 5 mice,
      respectively). Its spatial distribution was determined by punch samples taken
      from the ischemic core and penumbra and further confirmed using an enzyme
      histochemistry technique (n = 4). Levels of PAR1 were determined using western
      blot. RESULTS: Two hours following pMCAo, thrombin activity in the stroke core
      was already significantly higher than the contralateral area (11 +/- 5 vs. 2 +/-
      1 mU/ml). At 5 and 24 h, thrombin activity continued to rise linearly (r = 0.998,
      p = 0.001) and to expand in the ischemic hemisphere beyond the ischemic core
      reaching deleterious levels of 271 +/- 117 and 123 +/- 14 mU/ml (mean +/- SEM) in
      the basal ganglia and ischemic cortex, respectively. The peak elevation of
      thrombin activity in the ischemic core that was confirmed by fluorescence
      histochemistry was in good correlation with the infarcts areas. PAR1 levels in
      the ischemic core decreased as stroke progressed and thrombin activity increased.
      CONCLUSION: In conclusion, there is a time- and space-related increase in brain
      thrombin activity in acute ischemic stroke that is closely related to the
      progression of brain damage. These results may be useful in the development of
      therapeutic strategies for ischemic stroke that involve the thrombin-PAR1 pathway
      in order to prevent secondary thrombin related brain damage.

PMID- 28443062
TI  - Somatosensory Misrepresentation Associated with Chronic Pain: Spatiotemporal
      Correlates of Sensory Perception in a Patient following a Complex Regional Pain
      Syndrome Spread.
AB  - Chronic pain is suggested to be linked to reorganization processes in the
      sensorimotor cortex. In the current study, the somatosensory representation of
      the extremities was investigated in a patient with a complex regional pain
      syndrome (CRPS) that initially occurred in the right hand and arm and spread
      later into the left hand and right leg. After the spread, magnetoencephalographic
      recordings in conjunction with somatosensory stimulation revealed that the
      clinical symptoms were associated with major changes in the primary somatosensory
      representation. Tactile stimulation of body parts triggering CRPS-related pain
      elicited activity located in the left primary somatosensory region corresponding
      to the right hand representation, where the CRPS initially appeared. Solely the
      unaffected left foot was observed to have a regular S1 representation. The pain
      distribution pattern was matching the cortical somatosensory misrepresentation
      suggesting that cortical reorganization processes might contribute and possibly
      underlie the development and spread of the CRPS.

PMID- 28443064
TI  - Loss of Vagal Sensitivity to Cholecystokinin in Rats Born with Intrauterine
      Growth Retardation and Consequence on Food Intake.
AB  - Perinatal malnutrition is associated with low birth weight and an increased risk
      of developing metabolic syndrome in adulthood. Modification of food intake (FI)
      regulation was observed in adult rats born with intrauterine growth retardation
      induced by maternal dietary protein restriction during gestation and maintained
      restricted until weaning. Gastrointestinal peptides and particularly
      cholecystokinin (CCK) play a major role in short-term regulation of FI by
      relaying digestive signals to the hindbrain via the vagal afferent nerve (VAN).
      We hypothesized that vagal sensitivity to CCK could be affected in rats suffering
      from undernutrition [low protein (LP)] during fetal and postnatal life, leading
      to an altered gut-brain communication and impacting satiation. Our aim was to
      study short-term FI along with signals of appetite and satiation in adult LP rats
      compared to control rats. The dose-response to CCK injection was investigated on
      FI as well as the associated signaling pathways activated in nodose ganglia. We
      showed that LP rats have a reduced first-meal satiety ratio after a fasting
      period associated to a higher postprandial plasmatic CCK release, a reduced
      sensitivity to CCK when injected at low concentration and a reduced presence of
      CCK-1 receptor in nodose ganglia. Accordingly, the lower basal and CCK-induced
      phosphorylation of calcium/calmodulin-dependent protein kinase in nodose ganglia
      of LP rats could reflect an under-expressed vanilloid family of transient
      receptor potential cation channels on VAN. Altogether, the present data
      demonstrated a reduced vagal sensitivity to CCK in LP rats at adulthood, which
      could contribute to deregulation of FI reported in this model.

PMID- 28443063
TI  - On the Molecular Evolution of Leptin, Leptin Receptor, and Endospanin.
AB  - Over a decade passed between Friedman's discovery of the mammalian leptin gene
      (1) and its cloning in fish (2) and amphibians (3). Since 2005, the concept of
      gene synteny conservation (vs. gene sequence homology) was instrumental in
      identifying leptin genes in dozens of species, and we now have leptin genes from
      all major classes of vertebrates. This database of LEP (leptin), LEPR (leptin
      receptor), and LEPROT (endospanin) genes has allowed protein structure modeling,
      stoichiometry predictions, and even functional predictions of leptin function for
      most vertebrate classes. Here, we apply functional genomics to model hundreds of
      LEP, LEPR, and LEPROT proteins from both vertebrates and invertebrates. We
      identify conserved structural motifs in each of the three leptin signaling
      proteins and demonstrate Drosophila Dome protein's conservation with vertebrate
      leptin receptors. We model endospanin structure for the first time and identify
      endospanin paralogs in invertebrate genomes. Finally, we argue that leptin is not
      an adipostat in fishes and discuss emerging knockout models in fishes.

PMID- 28443066
TI  - Judging the Fertility Protective Effect of GnRH Agonists in Chemotherapy-It Is a
      Matter of Perspective.

PMID- 28443065
TI  - Hemoglobin-Improved Protection in Cultured Cerebral Cortical Astroglial Cells:
      Inhibition of Oxidative Stress and Caspase Activation.
AB  - Oxidative stress plays a major role in triggering astroglial cell death in
      diverse neuropathological conditions such as ischemia and neurodegenerative
      diseases. Numerous studies indicate that hemoglobin (Hb) is expressed in both
      resting and reactive glia cells, but nothing is known regarding a possible role
      of Hb on astroglial cell survival. Thus, the purpose of the present study was to
      investigate the potential glioprotective effect of Hb on hydrogen peroxide (H2O2)
      induced oxidative stress and apoptosis in cultured rat astrocytes. Our study
      demonstrates that administration of graded concentrations of Hb (10-12 to 10-6 M)
      to H2O2-treated astrocytes reduces cell death in a concentration-dependent
      manner. H2O2 treatment induces the accumulation of reactive oxygen species (ROS)
      and nitric oxide (NO), a drop of the mitochondrial membrane potential, and a
      stimulation of caspase-3/7 activity. Exposure of H2O2-treated cells to Hb was
      accompanied by marked attenuations of ROS and NO surproductions, mitochondrial
      membrane potential reduction, and caspase-3/7 activity increase. The protective
      action of Hb was blocked by the protein kinase A (PKA) inhibitor H89, the protein
      kinase C (PKC) inhibitor chelerythrine, and the mitogen-activated protein (MAP)
      kinase kinase (MEK) inhibitor U0126. Taken together, these data demonstrate for
      the first time that Hb is a glioprotective factor that protects astrocytes from
      apoptosis induced by oxidative stress and suggest that Hb may confer
      neuroprotection in neurodegenerative diseases. The anti-apoptotic activity of Hb
      on astrocytes is mediated through the PKA, PKC, and MAPK transduction pathways
      and can be accounted for by inhibition of oxidative stress-induced mitochondrial
      dysfunctions and caspase activation.

PMID- 28443067
TI  - Remarks on the Prolactin Hypothesis of Peripartum Cardiomyopathy.

PMID- 28443068
TI  - Evaluation of the Probiotic Strain Bifidobacterium longum subsp. Infantis CECT
      7210 Capacities to Improve Health Status and Fight Digestive Pathogens in a
      Piglet Model.
AB  - Probiotics have been demonstrated to be useful to enhance gut health and prevent
      gastrointestinal infections. The objective of this study is to demonstrate the
      potential of the probiotic strain Bifidobacterium longum subsp. infantis CECT
      7210 (B. infantis IM1) to prevent and fight intestinal disease by using a
      Salmonella Typhimurium (Trial 1) or an enterotoxigenic Escherichia coli K88
      (Trial 2) oral challenge in a weaning piglet model. Seventy-two piglets were used
      in each trial. After an adaptation period, animals were orally challenged. One
      animal per pen was euthanized at Days 4 and 8/9 (Trial 1/Trial 2) post
      inoculation (PI). Animal performance, clinical signs, pathogen excretion,
      fermentation, immune response, and intestinal morphology were evaluated. In Trial
      1, most parameters responded to the challenge, whereas, in Trial 2, effects were
      much milder. Consistent effects of the probiotic were detected in both
      experiments: Reduction of pathogen excretion (P = 0.043 on Day 3 PI, Trial 1) or
      ileal colonization (33% reduction of animals with countable coliforms; P = 0.077,
      Trial 2); increases in intraepithelial lymphocytes (P = 0.002 on Day 8 PI in
      Trial 1, P = 0.091 on Day 4 PI in Trial 2), and improvement of the fermentation
      profile by increasing butyric acid in non-challenged animals [P challenge *
      probiotic (interaction) = 0.092 in Trial 1 and P = 0.056 in Trial 2] concomitant
      with an enhancement of the villus:crypt ratio on Day 8/9 PI (P interaction =
      0.091 for Trial 1 and P = 0.006 for Trial 2). Challenged animals treated with the
      probiotic showed reduced feed intakes (P interaction = 0.019 in Trial 1 and P =
      0.020 in Trial 2) and had lower short-chain fatty acid concentrations in the
      colon (P interaction = 0.008 in Trial 1 and P = 0.082 in Trial 2). In conclusion,
      this probiotic demonstrated potential to reduce the intestinal colonization by
      pathogens and to stimulate local immune response. However, effects on feed
      intake, microbial fermentation, and intestinal architecture showed a differential
      pattern between challenged and non-challenged animals. Effects of the probiotic
      intervention were dependent on the structure of the ecosystem in which it was
      applied.

PMID- 28443069
TI  - Long-Term Enrichment of Stress-Tolerant Cellulolytic Soil Populations following
      Timber Harvesting Evidenced by Multi-Omic Stable Isotope Probing.
AB  - Soil management is vital for maintaining the productivity of commercial forests,
      yet the long-term impact of timber harvesting on soil microbial communities
      remains largely a matter of conjecture. Decomposition of plant biomass, comprised
      mainly of lignocellulose, has a broad impact on nutrient cycling, microbial
      activity and physicochemical characteristics of soil. At "Long-term Soil
      Productivity Study" sites in California dominated by Ponderosa pine, we tested
      whether clear-cut timber harvesting, accompanied by varying degrees of organic
      matter (OM) removal, affected the activity and structure of the cellulose
      degrading microbial populations 16 years after harvesting. Using a variety of
      experimental approaches, including stable isotope probing with 13C-labeled
      cellulose in soil microcosms, we demonstrated that harvesting led to a decrease
      in net respiration and cellulolytic activity. The decrease in cellulolytic
      activity was associated with an increased relative abundance of thermophilic,
      cellulolytic fungi (Chaetomiaceae), coupled with a decreased relative abundance
      of cellulolytic bacteria, particularly members of Opitutaceae, Caulobacter, and
      Streptomycetaceae. In general, harvesting led to an increase in stress-tolerant
      taxa (i.e., also non-cellulolytic taxa), though our results indicated that OM
      retention mitigated population shifts via buffering against abiotic changes.
      Stable-isotope probing improved shotgun metagenome assembly by 20-fold and
      enabled the recovery of 10 metagenome-assembled genomes of cellulolytic bacteria
      and fungi. Our study demonstrates the putative cellulolytic activity of a number
      of uncultured taxa and highlights the mineral soil layer as a reservoir of
      uncharacterized diversity of cellulose-degraders. It also and contributes to a
      growing body of research showing persistent changes in microbial community
      structure in the decades following forest harvesting.

PMID- 28443071
TI  - Deletion of Lipoteichoic Acid Synthase Impacts Expression of Genes Encoding Cell
      Surface Proteins in Lactobacillus acidophilus.
AB  - Lactobacillus acidophilus NCFM is a well-characterized probiotic microorganism,
      supported by a decade of genomic and functional phenotypic investigations. L.
      acidophilus deficient in lipoteichoic acid (LTA), a major immunostimulant in Gram
      positive bacteria, has been shown to shift immune system responses in animal
      disease models. However, the pleiotropic effects of removing LTA from the cell
      surface in lactobacilli are unknown. In this study, we surveyed the global
      transcriptional and extracellular protein profiles of two strains of L.
      acidophilus deficient in LTA. Twenty-four differentially expressed genes specific
      to the LTA-deficient strains were identified, including a predicted heavy metal
      resistance operon and several putative peptidoglycan hydrolases. Cell morphology
      and manganese sensitivity phenotypes were assessed in relation to the putative
      functions of differentially expressed genes. LTA-deficient L. acidophilus
      exhibited elongated cellular morphology and their growth was severely inhibited
      by elevated manganese concentrations. Exoproteomic surveys revealed distinct
      changes in the composition and relative abundances of several extracellular
      proteins and showed a bias of intracellular proteins in LTA-deficient strains of
      L. acidophilus. Taken together, these results elucidate the impact of ltaS
      deletion on the transcriptome and extracellular proteins of L. acidophilus,
      suggesting roles of LTA in cell morphology and ion homeostasis as a structural
      component of the Gram positive cell wall.

PMID- 28443070
TI  - Crystal Structure of Glyceraldehyde-3-Phosphate Dehydrogenase from the Gram
      Positive Bacterial Pathogen A. vaginae, an Immunoevasive Factor that Interacts
      with the Human C5a Anaphylatoxin.
AB  - The Gram-positive anaerobic human pathogenic bacterium Atopobium vaginae causes
      most diagnosed cases of bacterial vaginosis as well as opportunistic infections
      in immunocompromised patients. In addition to its well-established role in
      carbohydrate metabolism, D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from
      Streptococcus pyogenes and S. pneumoniae have been reported to act as
      extracellular virulence factors during streptococcal infections. Here, we report
      the crystal structure of GAPDH from A. vaginae (AvGAPDH) at 2.19 A resolution.
      The refined model has a crystallographic Rfree of 22.6%. AvGAPDH is a
      homotetramer wherein each subunit is bound to a nicotinamide adenine dinucleotide
      (NAD+) molecule. The AvGAPDH enzyme fulfills essential glycolytic as well as
      moonlight (non-glycolytic) functions, both of which might be targets of
      chemotherapeutic intervention. We report that AvGAPDH interacts in vitro with the
      human C5a anaphylatoxin and inhibits C5a-specific granulocyte chemotaxis, thereby
      suggesting the participation of AvGAPDH in complement-targeted immunoevasion in a
      context of infection. The availability of high-quality structures of AvGAPDH and
      other homologous virulence factors from Gram-positive pathogens is critical for
      drug discovery programs. In this study, sequence and structural differences
      between AvGAPDH and related bacterial and eukaryotic GAPDH enzymes are reported
      in an effort to understand how to subvert the immunoevasive properties of GAPDH
      and evaluate the potential of AvGAPDH as a druggable target.

PMID- 28443072
TI  - Distribution of Integrons and Phylogenetic Groups among Enteropathogenic
      Escherichia coli Isolates from Children <5 Years of Age in Delhi, India.
AB  - Integrons by means of horizontal gene transfer carry multidrug resistance genes
      (MDR) among bacteria, including E. coli. The aim of this study was to determine
      the antibiotic resistance profiles and the genes associated with them, to gain
      insights in the distribution of phylogroups, prevalence, and characterization of
      class 1, 2 and 3 integrons among Enteropathogenic E. coli (EPEC) isolates, from
      children upto 5 years of age from Delhi and National Capital Region (NCR), India.
      A total of 120 E. coli isolates, including 80 from diarrheagenic E. coli (cases)
      and 40 from healthy isolates (controls) were recruited in this study. After
      isolation of E. coli, screening for EPEC was done by conventional multiplex PCR.
      Antibiotic suseptibility test was performed using disk diffusion method and
      further confirmed by minimum inhibitory concentration (MICs) by E-test. The
      presence and characterization of integrons and antimicrobial resistance genes
      were performed by PCR and DNA sequencing. Phylogeny determination was carried out
      by quadruplex PCR. EPEC strains were found in 64 of the 80 diarrheagenic cases,
      out of which 38 were MDR. In the 40 healthy controls, 23 were found to be EPEC
      strain, out of which only 2 were MDR. Amongst 80 diarrheagenic cases, class 1
      integron were observed in 43 isolates, class 2 integron in 12 isolates and 9
      isolates were found with co-existence of both. Similarly, in healthy controls;
      class 1 integron in 9 and class 2 integron in 7 isolates were observed with co
      existence in 3 isolates. None of the isolates included class 3 integron. The dfr
      was the most commonly identified gene cassette within the integron-positive
      isolates. Phylogenetic studies showed considerable representation of phylogroup
      B2 in both diarrheagenic cases and healthy controls. This study reiterates the
      importance of class 1 integron predominantly for acquisition of antibiotic
      resistance genes among EPEC isolates. Furthermore, it also ascertains the
      possible association between multidrug resistance and presence of integrons.
      Approximately 91% of isolates were easily assigned to their respective
      phylogroups. Assessment of the relationship between antibiotic resistance and
      dominant phylogroups detected was also attempted. This study also highlights the
      increased burden of antimicrobial resistance in healthy controls.

PMID- 28443073
TI  - Feed Supplementation with Red Seaweeds, Chondrus crispus and Sarcodiotheca
      gaudichaudii, Reduce Salmonella Enteritidis in Laying Hens.
AB  - Salmonella Enteritidis is vertically transmitted to eggs from laying hens through
      infected ovaries and oviducts. S. Enteritidis can also penetrate the eggshell
      from contaminated feces. Reducing S. Enteritidis in laying hens is vital to
      provide safer eggs and minimize the spread of salmonellosis to humans.
      Antibiotics have been widely used to control bacterial diseases in broilers and
      laying hens. However, there is a major concern that the use of antibiotics leads
      to the development of antibiotic resistance and adverse effects on microbiota of
      the treated birds. Thus, there is an interest in developing alternatives to
      antibiotics, such as dietary prebiotics. In the present study, feed supplemented
      with the red seaweeds: Chondrus crispus (CC) or Sarcodiotheca gaudichaudii (SG),
      was offered to laying hens late in production to control S. Enteritidis. Diets
      contained one of the following; 2% or 4% Chondrus crispus (CC2, and CC4,
      respectively) or Sarcodiotheca gaudichaudii (SG2 and SG4, respectively).
      Chlortetracycline was used in the positive control diet. During week-4, 48 birds
      were orally challenged with 2 * 109 CFU/mL of S. Enteritidis. Eggs and fecal
      samples were collected 1, 3, 5, and 7 days' post inoculation. Birds were
      euthanized and organs (ceca, ovary, liver, and spleen) were sampled and analyzed
      for the presence of S. Enteritidis, 7 days' post inoculation. Results showed that
      seaweed reduced the negative effect on body weight and egg production in S.
      Enteritidis-challenged laying hens. Analysis of fecal samples showed that the
      antibiotic (CTC) reduced S. Enteritidis in the intestinal tract and fecal
      samples, 3 days' post inoculation. Fecal samples from Chlortetracycline and CC4
      supplemented birds tested negative for S. Enteritidis on days 5 and 7 post
      inoculation (lowest detection limit = 10-1). S. Enteritidis colonization in the
      ceca was also significantly reduced in birds fed CC (4%) and Chlortetracycline.
      Blood serum profiles revealed that there were no significant differences in serum
      aspartate aminotransferase (AST) and sodium. However, the level of serum
      immunoglobulin (IgA) was higher in the CC4 treatment. The relative abundance of
      Lactobacillus acidophilus was significantly higher in CC4 while, the abundance of
      the pathogenic bacteria, Clostridium perfringens and Salmonella Enteritidis were
      reduced compared to control. Results indicate that feed supplemented with 4% CC
      is effective in providing protection against Salmonella Enteritidis colonization
      in laying hens.

PMID- 28443074
TI  - Zinc-Dependent Transcriptional Regulation in Paracoccus denitrificans.
AB  - Zinc homeostasis is critical for bacterial survival and is mediated largely at
      the transcriptional level by the regulation of zinc uptake and efflux genes. Here
      we use RNA-seq to assess transcriptional changes as a result of zinc limitation
      in the denitrifying bacterium Paracoccus denitrificans. The results identify the
      differential expression of 147 genes, most of which were upregulated in zinc
      depleted medium. Included in this set of genes are a large number of transition
      metal transporters, several transcription factors, and hypothetical proteins.
      Intriguingly, genes encoding nitric oxide reductase (norCB) and nitrite reductase
      (nirS) were also upregulated. A Zur consensus binding motif was identified in the
      promoters of the most highly upregulated genes. The zinc uptake regulator (Zur)
      from this organism was also characterized and shown to bind to the Zur motif in a
      zinc-dependent manner. This work expands our current understanding of the
      transcriptional response of gram-negative bacteria to zinc limitation and
      identifies genes involved in denitrification as part of the Zur regulon.

PMID- 28443075
TI  - GRIM-19 Restricts HCV Replication by Attenuating Intracellular Lipid
      Accumulation.
AB  - Gene-associated with retinoid-interferon-induced mortality 19 (GRIM-19) targets
      multiple signaling pathways involved in cell death and growth. However, the role
      of GRIM-19 in the pathogenesis of hepatitis virus infections remains unexplored.
      Here, we investigated the restrictive effects of GRIM-19 on the replication of
      hepatitis C virus (HCV). We found that GRIM-19 protein levels were reduced in HCV
      infected Huh7 cells and Huh7 cells harboring HCV replicons. Moreover, ectopically
      expressed GRIM-19 caused a reduction in both intracellular viral RNA levels and
      secreted viruses in HCVcc-infected cell cultures. The restrictive effect on HCV
      replication was restored by treatment with siRNA against GRIM-19. Interestingly,
      GRIM-19 overexpression did not alter the level of phosphorylated STAT3 or its
      subcellular distribution. Strikingly, forced expression of GRIM-19 attenuated an
      increase in intracellular lipid droplets after oleic acid (OA) treatment or HCVcc
      infection. GRIM-19 overexpression abrogated fatty acid-induced upregulation of
      sterol regulatory element-binding transcription factor-1 (SREBP-1c), resulting in
      attenuated expression of its target genes such as fatty acid synthase (FAS) and
      acetyl CoA carboxylase (ACC). Treatment with OA or overexpression of SREBP-1c in
      GRIM-19-expressing, HCVcc-infected cells restored HCV replication. Our results
      suggest that GRIM-19 interferes with HCV replication by attenuating intracellular
      lipid accumulation and therefore is an anti-viral host factor that could be a
      promising target for HCV treatment.

PMID- 28443076
TI  - rstB Regulates Expression of the Photobacterium damselae subsp. damselae Major
      Virulence Factors Damselysin, Phobalysin P and Phobalysin C.
AB  - The marine pathogenic bacterium Photobacterium damselae subsp. damselae causes
      septicemia in marine animals and in humans. The pPHDD1 plasmid-encoded hemolysins
      damselysin (Dly) and phobalysin P (PhlyP), and the chromosome-encoded hemolysin
      phobalysin C (PhlyC) constitute its main virulence factors. However, the
      mechanisms by which expression of these three hemolysins is regulated remain
      unknown. Here we report the isolation of a mini-Tn10 transposon mutant which
      showed a strong impairment in its hemolytic activity. The transposon disrupted a
      putative sensor histidine kinase gene vda_000600 (rstB), which together with
      vda_000601 (rstA) is predicted to encode a putative two-component regulatory
      system. This system showed to be homologous to the Vibrio cholerae CarSR/VprAB
      and Escherichia coli RstAB systems. Reconstruction of the mutant by allelic
      exchange of rstB showed equal impairment in hemolysis, and complementation with a
      plasmid expressing rstAB restored hemolysis to wild-type levels. Remarkably, we
      demonstrated by promoter expression analyses that the reduced hemolysis in the
      rstB mutant was accompanied by a strong decrease in transcription activities of
      the three hemolysin genes dly (damselysin), hlyApl (phobalysin P) and hlyAch
      (phobalysin C). Thus, RstB, encoded in the small chromosome, regulates plasmid
      and chromosomal virulence genes. We also found that reduced expression of the
      three virulence genes correlated with a strong decrease in virulence in a sea
      bass model, demonstrating that RstB constitutes a master regulator of the three
      P. damselae subsp. damselae hemolysins and plays critical roles in the
      pathogenicity of this bacterium. This study represents the first evidence of a
      direct role of a RstAB-like system in the regulation of bacterial toxins.

PMID- 28443077
TI  - Molecular Dynamics Simulation of the Influenza A(H3N2) Hemagglutinin Trimer
      Reveals the Structural Basis for Adaptive Evolution of the Recent Epidemic Clade
      3C.2a.
AB  - Influenza A(H3N2) has been a major cause of seasonal influenza in humans since
      1968, and has evolved by antigenic drift under the constantly changing human herd
      immunity. Increasing evidence suggests that the antigenic change occasionally
      occurred concomitant with the alterations of the N-glycosylation site profile and
      hemagglutination activity of the virion surface protein hemagglutinin (HA).
      However, the structural basis of these changes remains largely unclear. To
      address this issue, we performed molecular dynamics simulations of the
      glycosylated HA trimers of the A(H3N2), which has a novel pattern of Asn-X
      Ser/Thr sequons unique in the new A(H3N2) epidemic clade 3C.2a and is
      characterized by attenuated ability to agglutinate nonhuman erythrocytes.
      Comparison of the equilibrated structures of the glycosylated HA trimers with and
      without the 3C.2a-specific mutations reveals that the mutations could induce a
      drastic reduction in the apical space for the ligand binding via glycan-shield
      rearrangement. The results suggest that the 3C.2a strain has evolved an HA
      structure that is advantageous for evading pre-existing antibodies, while also
      increasing the ligand binding specificity. These findings have structural
      implications for our understanding of the phenotypic changes, evolution, and fate
      of influenza A(H3N2).

PMID- 28443078
TI  - Phytochemical Characterization of Terminalia catappa Linn. Extracts and Their
      antifungal Activities against Candida spp.
AB  - Terminalia catappa Linn bark is used to treat dysentery by various populations in
      Southeast Asian countries, and its leaves have also been used in traditional
      medicine to treat hepatitis in India and the Philippines. Here, the antifungal
      actions of crude hydro-alcoholic extract (TcHE) and fractions from T. catappa
      leaves were assessed via the agar diffusion and microdilution tests on Candida
      reference strains and clinical isolates from patients with acquired
      immunodeficiency syndrome (AIDS). Additionally, the potential cytotoxic effects
      of TcHE were assessed on cultured human peripheral blood mononuclear cells
      (PBMC). T. catappa fractions and sub-fractions were analyzed by gas
      chromatography coupled to mass spectrometry with electron impact (GC/MS/EI), high
      performance liquid chromatography coupled to mass spectrometry "electrospray"
      ionization in positive mode (HPLC/MS/MS/ESI+) and hydrogen nuclear magnetic
      resonance (1HNMR). TcHE and its fractions were able to inhibit the growth of all
      tested Candida strains with the n-butanol (FBuOH) fraction presenting the best
      antifungal activity. Testing of different FBuOH sub-fractions (SF) showed that
      SF10 was the most active against Candida spp. Fractioning of SF10 demonstrated
      that 5 out of its 15 sub-fractions were active against Candida spp., with SF10.5
      presenting the highest activity. Chemical analysis of SF10 detected hydrolysable
      tannins (punicalin, punicalagin), gallic acid and flavonoid C-glycosides.
      Overall, the results showed that T. catappa L. leaf extract, fractions and sub
      fractions were antifungal against Candida spp. and may be useful to treat
      diseases caused by this fungus.

PMID- 28443080
TI  - Genome Sequencing Reveals the Complex Polysaccharide-Degrading Ability of Novel
      Deep-Sea Bacterium Flammeovirga pacifica WPAGA1.
AB  - Flammeovirga pacifica strain WPAGA1 is a Gram-negative, polysaccharide-degrading
      bacterium isolated from the marine sediment of the West Pacific Ocean. This
      strain is a cosmopolitan marine bacterium that uses complex polysaccharides as
      exclusive source of carbon and energy and plays a key role in the marine carbon
      cycle. Genome sequence analysis of strain WPAGA1 revealed that the assembled fine
      genome contains 6,610,326 bp with 32.89% G+C content, 5036 open reading frames
      (ORFs) and abundant genomic elements. Amongst these ORFs, 1022 genes encoding
      carbohydrate enzymes were found in the F. pacifica WPAGA1 genome. In addition,
      abundant putative enzymes involved in degrading polysaccharide were found. These
      enzymes include amylase, xylosidase, cellulase, alginate lyase, pectate lyase,
      rhamnogalacturonan lyase, chitinase, carrageenase, heparinase and fucosidase. To
      further investigate the use of these polysaccharides in strain WPAGA1, a
      schematic of various polysaccharide-degrading metabolic pathways were deduced
      from the genome sequence. This study showed that strain WPAGA1 may serve as a
      potential candidate for research of glycometabolism and have potential
      biotechnological and industrial applications and play key roles in the marine
      carbon cycle.

PMID- 28443079
TI  - Pleomorphism and Viability of the Lyme Disease Pathogen Borrelia burgdorferi
      Exposed to Physiological Stress Conditions: A Correlative Cryo-Fluorescence and
      Cryo-Scanning Electron Microscopy Study.
AB  - To understand the response of the Lyme disease spirochete Borrelia burgdorferi
      exposed to stress conditions and assess the viability of this spirochete, we used
      a correlative cryo-fluorescence and cryo-scanning microscopy approach. This
      approach enables simple exposition of bacteria to various experimental conditions
      that can be stopped at certain time intervals by cryo-immobilization, examination
      of cell viability without necessity to maintain suitable culture conditions
      during viability assays, and visualization of structures in their native state at
      high magnification. We focused on rare and transient events e.g., the formation
      of round bodies and the presence of membranous blebs in spirochetes exposed to
      culture medium, host sera either without or with the bacteriolytic effect and
      water. We described all crucial steps of the workflow, particularly the influence
      of freeze-etching and accelerating voltage on the visualization of topography.
      With the help of newly designed cryo-transport device, we achieved greater
      reproducibility.

PMID- 28443081
TI  - Helicobacter pullorum: An Emerging Zoonotic Pathogen.
AB  - Helicobacter pullorum (H.pullorum) commonly colonizes the gastrointestinal tract
      of poultry causing gastroenteritis. The bacterium may be transmitted to humans
      through contaminated meat where it has been associated with colitis and
      hepatitis. Despite the high prevalence of H. pullorum observed in poultry, little
      is known about the mechanisms by which this bacterium establishes infection in
      host and its virulence determinants. In this article we aim to provide an
      overview of this emerging zoonotic pathogen; its general characteristics, hosts,
      prevalence, and transmission as well as its pathogenic potential. We also discuss
      possible control strategies and risk of disease emergence.

PMID- 28443082
TI  - Inbred Mouse Populations Exhibit Intergenerational Changes in Intestinal
      Microbiota Composition and Function Following Introduction to a Facility.
AB  - Inbred mice are used to investigate many aspects of human physiology, including
      susceptibility to disease and response to therapies. Despite increasing evidence
      that the composition and function of the murine intestinal microbiota can
      substantially influence a broad range of experimental outcomes, relatively little
      is known about microbiome dynamics within experimental mouse populations. We
      investigated changes in the intestinal microbiome between C57BL/6J mice spanning
      six generations (assessed at generations 1, 2, 3, and 6), following their
      introduction to a stringently controlled facility. Fecal microbiota composition
      and function were assessed by 16S rRNA gene amplicon sequencing and liquid
      chromatography mass spectrometry, respectively. Significant divergence of the
      intestinal microbiota between founder and second generation mice, as well as
      continuing inter-generational variance, was observed. Bacterial taxa whose
      relative abundance changed significantly through time included Akkermansia,
      Turicibacter, and Bifidobacterium (p < 0.05), all of which are recognized as
      having the potential to substantially influence host physiology. Shifts in
      microbiota composition were mirrored by corresponding differences in the fecal
      metabolome (r = 0.57, p = 0.0001), with notable differences in levels of
      tryptophan pathway metabolites and amino acids, including glutamine, glutamate
      and aspartate. We related the magnitude of changes in the intestinal microbiota
      and metabolome characteristics during acclimation to those observed between
      populations housed in separate facilities, which differed in regards to
      husbandry, barrier conditions and dietary intake. The microbiome variance
      reported here has implications for experimental reproducibility, and as a
      consequence, experimental design and the interpretation of research outcomes
      across wide range of contexts.

PMID- 28443083
TI  - Intracellular Localization, Interactions and Functions of Capsicum Chlorosis
      Virus Proteins.
AB  - Tospoviruses are among the most devastating viruses of horticultural and field
      crops. Capsicum chlorosis virus (CaCV) has emerged as an important pathogen of
      capsicum and tomato in Australia and South-east Asia. Present knowledge about
      CaCV protein functions in host cells is lacking. We determined intracellular
      localization and interactions of CaCV proteins by live plant cell imaging to gain
      insight into the associations of viral proteins during infection. Proteins were
      transiently expressed as fusions to autofluorescent proteins in leaf epidermal
      cells of Nicotiana benthamiana and capsicum. All viral proteins localized at
      least partially in the cell periphery suggestive of cytoplasmic replication and
      assembly of CaCV. Nucleocapsid (N) and non-structural movement (NSm) proteins
      localized exclusively in the cell periphery, while non-structural suppressor of
      silencing (NSs) protein and Gc and Gn glycoproteins accumulated in both the cell
      periphery and the nucleus. Nuclear localization of CaCV Gn and NSs is unique
      among tospoviruses. We validated nuclear localization of NSs by
      immunofluorescence in protoplasts. Bimolecular fluorescence complementation
      showed self-interactions of CaCV N, NSs and NSm, and heterotypic interactions of
      N with NSs and Gn. All interactions occurred in the cytoplasm, except NSs self
      interaction was exclusively nuclear. Interactions of a tospoviral NSs protein
      with itself and with N had not been reported previously. Functionally, CaCV NSs
      showed strong local and systemic RNA silencing suppressor activity and appears to
      delay short-distance spread of silencing signal. Cell-to-cell movement activity
      of NSm was demonstrated by trans-complementation of a movement-defective
      tobamovirus replicon. CaCV NSm localized at plasmodesmata and its transient
      expression led to the formation of tubular structures that protruded from
      protoplasts. The D155 residue in the 30K-like movement protein-specific LxD/N50
      70G motif of NSm was critical for plasmodesmata localization and movement
      activity. Compared to other tospoviruses, CaCV proteins have both conserved and
      unique properties in terms of in planta localization, interactions and protein
      functions which will effect viral multiplication and movement in host plants.

PMID- 28443085
TI  - Commentary: A bacterial global regulator forms a prion.

PMID- 28443084
TI  - Gene Expression Profiling of Transcription Factors of Helicobacter pylori under
      Different Environmental Conditions.
AB  - Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric
      mucosa and causes peptic ulcers and gastric carcinoma. H. pylori strain 26695 has
      a small genome (1.67 Mb), which codes for few known transcriptional regulators
      that control bacterial metabolism and virulence. We analyzed by qRT-PCR the
      expression of 16 transcriptional regulators in H. pylori 26695, including the
      three sigma factors under different environmental conditions. When bacteria were
      exposed to acidic pH, urea, nickel, or iron, the sigma factors were
      differentially expressed with a particularly strong induction of fliA. The
      regulatory genes hrcA, hup, and crdR were highly induced in the presence of urea,
      nickel, and iron. In terms of biofilm formation fliA, flgR, hp1021, fur, nikR,
      and crdR were induced in sessile bacteria. Transcriptional expression levels of
      rpoD, flgR, hspR, hp1043, and cheY were increased in contact with AGS epithelial
      cells. Kanamycin, chloramphenicol, and tetracycline increased or decreased
      expression of regulatory genes, showing that these antibiotics affect the
      transcription of H. pylori. Our data indicate that environmental cues which may
      be present in the human stomach modulate H. pylori transcription.

PMID- 28443087
TI  - Human Skin RNases Offer Dual Protection against Invading Bacteria.

PMID- 28443086
TI  - Complete Molecular and Immunoprotective Characterization of Babesia microti
      Enolase.
AB  - The apicomplexan Babesia microti is the primary causative agent of human
      babesiosis, one of the most broadly distributed tick-borne diseases worldwide. B.
      microti undergoes a complex lifecycle within both the mammalian host and the tick
      vector, and employs several different specific molecular mechanisms to enter host
      cells. Enolase, the key glycolytic enzyme in intracellular glucose metabolism,
      can also be expressed on the parasite's outer surface, binds to human
      plasminogen, and coordinates apicomplexan parasite invasion of host cells,
      however, it lacks sorting sequences or lipoprotein anchor sites. In the present
      study, we isolated the coding gene of B. microti enolase (BmEno), expressed it
      within E. coli and purified the recombinant BmEno protein (rBmEno). Consequently,
      we confirmed cytoplasmic and surface localization of BmEno via
      immunofluorescence, and demonstrated that rBmEno catalyzes the dehydration of 2
      phospho-D-glycerate to phosphoenolpyruvate. Moreover, our results showed that
      rBmEno binds to human plasminogen, and that the lysine analog epsilon
      aminocaproic acid significantly inhibited this binding. Furthermore plasminogen
      bound to rBmEno converts to active plasmin. Additionally, actively immunizing
      mice with rBmEno could evoke a partial protective immunity against B. microti
      infection following challenge. In conclusion, B. microti enolase is a
      multifunctional cytoplasmic protein which is also expressed at the parasitic
      outer surface, facilitates binding to host plasminogen, and could partially
      protect hosts against parasite infection.

PMID- 28443088
TI  - Utilizing Anaerobic Fungi for Two-stage Sugar Extraction and Biofuel Production
      from Lignocellulosic Biomass.
AB  - Lignocellulosic biomass is a vast and underutilized resource for the production
      of sugars and biofuels. However, the structural complexity of lignocellulosic
      biomass and the need for multiple pretreatment and enzymatic steps for sugar
      release renders this process economically challenging. Here, we report a novel
      approach for direct, single container, exogenous enzyme-free conversion of
      lignocellulosic biomass to sugars and biofuels using the anaerobic fungal isolate
      strain C1A. This approach utilizes simple physiological manipulations for timely
      inhibition and uncoupling of saccharolytic and fermentative capabilities of
      strain C1A, leading to the accumulation of sugar monomers (glucose and xylose) in
      the culture medium. The produced sugars, in addition to fungal hyphal lysate, are
      subsequently converted by Escherichia coli strain K011 to ethanol. Using this
      approach, we successfully recovered 17.0% (w/w) of alkali-pretreated corn stover
      (20.0% of its glucan and xylan content) as sugar monomers in the culture media.
      More importantly, 14.1% of pretreated corn stover (17.1% of glucan and xylan
      content) was recovered as ethanol at a final concentration of 28.16 mM after the
      addition of the ethanologenic strain K011. The high ethanol yield obtained is due
      to its accumulation as a minor fermentation end product by strain C1A during its
      initial growth phase, the complete conversion of sugars to ethanol by strain
      K011, and the possible conversion of unspecified substrates in the hyphal lysate
      of strain C1A to ethanol by strain K011. This study presents a novel, versatile,
      and exogenous enzyme-free strategy that utilizes a relatively unexplored group of
      organisms (anaerobic fungi) for direct biofuel production from lignocellulosic
      biomass.

PMID- 28443089
TI  - Japanese Encephalitis Virus Exploits Dopamine D2 Receptor-phospholipase C to
      Target Dopaminergic Human Neuronal Cells.
AB  - Despite the availability of vaccines for Japanese encephalitis virus (JEV), the
      re-emerging virus remains a clinically important pathogen that causes acute
      encephalitis and permanent neuropsychiatric sequels. JEV highly targets
      dopaminergic neuron-rich brain regions including the thalamus and midbrain. The
      molecular mechanism contributing to the high susceptibility of these particular
      brain regions remains largely unclear. This study addressed whether this tissue
      tropism of JEV is associated with signaling of dopaminergic neurons. Three pieces
      of evidence indicate that JEV exploits dopamine signaling to facilitate its
      infection: (1) JEV infection modulates dopamine level; (2) a selective dopamine
      D2 receptor (D2R) agonist enhances JEV infection; and (3) stimulation of D2R
      activates phospholipase C (PLC) to enhance the surface expression of JEV
      binding/entry molecules, integrin beta3 and vimentin. Overall, JEV may exploit
      dopamine-mediated neuronal communication to increase the susceptibility of D2R
      expressing cells to JEV infection. This study identifies a potential underlying
      mechanism of viral invasiveness in the dopaminergic brain regions and suggests
      antiviral strategies against viral infection by targeting D2R-PLC signaling.

PMID- 28443091
TI  - Natural Killer Group 2D Ligand Depletion Reconstitutes Natural Killer Cell
      Immunosurveillance of Head and Neck Squamous Cell Carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and
      aggressive tumor originating from the epithelial lining of the upper aero
      digestive tract accounting for 300,000 annual deaths worldwide due to failure of
      current therapies. The natural killer group 2D (NKG2D) receptors on natural
      killer (NK) cells and several T cell subsets play an important role for
      immunosurveillance of HNSCC and are thus targeted by tumor immune evasion
      strategies in particular by shedding of various NKG2D ligands (NKG2DLs). Based on
      plasma and tumor samples of 44 HNSCC patients, we found that despite
      compositional heterogeneity the total plasma level of NKG2DLs correlates with NK
      cell inhibition and disease progression. Strikingly, based on tumor spheroids and
      primary tumors of HNSCC patients, we found that NK cells failed to infiltrate
      HNSCC tumors in the presence of high levels of NKG2DLs, demonstrating a novel
      mechanism of NKG2DL-dependent tumor immune escape. Therefore, the diagnostic
      acquisition of the plasma level of all NKG2DLs might be instrumental for
      prognosis and to decipher a patient cohort, which could benefit from restoration
      of NKG2D-dependent tumor immunosurveillance. Along these lines, we could show
      that removal of shed NKG2DLs (sNKG2DLs) from HNSCC patients' plasma restored NK
      cell function in vitro and in individual patients following surgical removal of
      the primary tumor. In order to translate these findings into a therapeutic
      setting, we performed a proof-of-concept study to test the efficacy of adsorption
      apheresis of sNKG2DLs from plasma after infusion of human MICA in rhesus monkeys.
      Complete removal of MICA was achieved after three plasma volume exchanges.
      Therefore, we propose adsorption apheresis of sNKG2DLs as a future
      preconditioning strategy to improve the efficacy of autologous and adoptively
      transferred immune cells in cellular cancer immunotherapy.

PMID- 28443092
TI  - Disarming Cellular Alarm Systems-Manipulation of Stress-Induced NKG2D Ligands by
      Human Herpesviruses.
AB  - The coevolution of viruses and their hosts led to the repeated emergence of
      cellular alert signals and viral strategies to counteract them. The herpesvirus
      family of viruses displays the most sophisticated repertoire of immune escape
      mechanisms enabling infected cells to evade immune recognition and thereby
      maintain infection. The herpesvirus family consists of nine viruses that are
      capable of infecting humans: herpes simplex virus 1 and 2 (HSV-1, HSV-2),
      varicella zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus
      (HCMV), roseoloviruses (HHV-6A, HHV-6B, and HHV-7), and Kaposi's-sarcoma
      associated herpesvirus (KSHV). Most of these viruses are highly prevalent and
      infect a vast majority of the human population worldwide. Notably, research over
      the past 15 years has revealed that cellular ligands for the activating receptor
      natural-killer group 2, member D (NKG2D)-which is primarily expressed on natural
      killer (NK) cells-are common targets suppressed during viral infection, i.e.,
      their surface expression is reduced in virtually all lytic herpesvirus infections
      by diverse mechanisms. Here, we review the viral mechanisms by which all
      herpesviruses known to date to downmodulate the expression of the NKG2D ligands.
      Also, in light of recent findings, we speculate about the importance of the
      emergence of eight different NKG2D ligands in humans and further allelic
      diversification during host and virus coevolution.

PMID- 28443090
TI  - Immunometabolic Regulations Mediated by Coinhibitory Receptors and Their Impact
      on T Cell Immune Responses.
AB  - Host immunity provides wide spectrum protection that serves to eradicate
      pathogens and cancer cells, while maintaining self-tolerance and immunological
      homeostasis. Ligation of the T cell receptor (TCR) by antigen activates signaling
      pathways that coordinately induce aerobic glycolysis, mitochondrial activity,
      anabolic metabolism, and T effector cell differentiation. Activation of PI3K,
      Akt, and mTOR triggers the switch to anabolic metabolism by inducing
      transcription factors such as Myc and HIF1, and the glucose transporter Glut1,
      which is pivotal for the increase of glucose uptake after T cell activation.
      Activation of MAPK signaling is required for glucose and glutamine utilization,
      whereas activation of AMPK is critical for energy balance and metabolic fitness
      of T effector and memory cells. Coinhibitory receptors target TCR-proximal
      signaling and generation of second messengers. Imbalanced activation of such
      signaling pathways leads to diminished rates of aerobic glycolysis and impaired
      mitochondrial function resulting in defective anabolic metabolism and altered T
      cell differentiation. The coinhibitory receptors mediate distinct and synergistic
      effects on the activation of signaling pathways thereby modifying metabolic
      programs of activated T cells and resulting in altered immune functions.
      Understanding and therapeutic targeting of metabolic programs impacted by
      coinhibitory receptors might have significant clinical implications for the
      treatment of chronic infections, cancer, and autoimmune diseases.

PMID- 28443093
TI  - A Novel Cervical Spinal Cord Window Preparation Allows for Two-Photon Imaging of
      T-Cell Interactions with the Cervical Spinal Cord Microvasculature during
      Experimental Autoimmune Encephalomyelitis.
AB  - T-cell migration across the blood-brain barrier (BBB) is a crucial step in the
      pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model
      of multiple sclerosis (MS). Two-photon intravital microscopy (2P-IVM) has been
      established as a powerful tool to study cell-cell interactions in inflammatory
      EAE lesions in living animals. In EAE, central nervous system inflammation is
      strongly pronounced in the spinal cord, an organ in which 2P-IVM imaging is
      technically very challenging and has been limited to the lumbar spinal cord.
      Here, we describe a novel spinal cord window preparation allowing to use 2P-IVM
      to image immune cell interactions with the cervical spinal cord microvascular
      endothelium during EAE. We describe differences in the angioarchitecture of the
      cervical spinal cord versus the lumbar spinal cord, which will entail different
      hemodynamic parameters in these different vascular beds. Using T cells as an
      example, we demonstrate the suitability of this novel methodology in imaging the
      post-arrest multistep T-cell extravasation across the cervical spinal cord
      microvessels. The novel methodology includes an outlook to the analysis of the
      cellular pathway of T-cell diapedesis across the BBB by establishing
      visualization of endothelial junctions in this vascular bed.

PMID- 28443094
TI  - Serum IgG Antibodies from Pregnant Women Reacting to Mimotopes of Simian Virus 40
      Large T Antigen, the Viral Oncoprotein.
AB  - Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in
      different human samples, whereas SV40 antibodies (Ab) were detected in human sera
      of cancer patients and healthy individuals, although with a lower prevalence.
      Previous studies carried out by the neutralization assay gave a SV40
      seroprevalence, in the general population, up to 8%, although higher rates, 12%,
      were detected in kidney transplant children, in a group of HIV-positive patients,
      and in healthy females. In this study, serum samples from pregnant women,
      together with those from non-pregnant women, were analyzed to check the
      prevalence of IgG Ab reacting to SV40 LT antigens. Serum samples were collected
      from pregnant and non-pregnant women, with the same mean age. Women were in the
      range of 15-48 years old. Samples were assayed by an indirect ELISA employing
      specific SV40 LT mimotopes as antigens, whereas functional analysis was performed
      by neutralization of the viral infectivity in cell cultures. As a control, sera
      were analyzed for Ab against BK polyomavirus (BKPyV), which is a human
      polyomavirus homologous to SV40. Statistical analyses employed chi-square with
      Yates' correction, and Student's t tests. Indirect ELISAs indicated that pregnant
      women tested SV40 LT-positive with a prevalence of 17% (23/134), whereas non
      pregnant women had a prevalence of 20% (36/180) (P > 0.05). Ab against BKPyV were
      detected with a prevalence of 80% in pregnant women and with a prevalence of 78%
      in non-pregnant women. These data indicate that SV40 infects at a low prevalence
      pregnant women. We may speculate that SV40, or a close human polyomavirus still
      undetected, could be transmitted from mother to fetus.

PMID- 28443095
TI  - Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory
      Biomarker Genes ARG1, BCL2L1, and MYC.
AB  - Ionizing radiation (IR) exposure of cells in vitro and in vivo triggers a complex
      cellular response among which modifications of gene expression have been
      consistently reported. Nevertheless, little is currently known about the
      transcriptionally responsive genes which play a role in the inflammation
      response. In order to improve our understanding of such transcriptional response
      to radiation in vivo, we simultaneously monitored the expression of 249 genes
      associated with the inflammation response over the course of the radiotherapy
      treatment in blood of patients treated for endometrial or head and neck cancer.
      We have identified genes whose transcriptional expression is either upregulated
      (ARG1, BCL2L1) or downregulated (MYC) several fold in vivo. These modifications
      were consistently detected across patients and further confirmed by quantitative
      real-time polymerase chain reaction (QRT-PCR); they were specifically significant
      toward the end of the radiotherapy treatment, 5 weeks following the first
      radiation fraction and more pronounced in endometrial patients (respectively,
      2.9, 4.1, and 1.8 times). Importantly, in an attempt to correlate expression
      levels with normal tissue reaction to IR, we also identified three other genes
      CD40, OAS2, and CXCR1 whose expression level fluctuations during radiotherapy
      were more pronounced in patients developing late normal tissue responses to
      curative radiotherapy after the end of the radiotherapy treatment. Overall, we
      identified inflammation-associated genes which are promising biomarkers of IR
      exposure and susceptibility to radiation-induced toxicity.

PMID- 28443097
TI  - Large Diversity of Functional Nanobodies from a Camelid Immune Library Revealed
      by an Alternative Analysis of Next-Generation Sequencing Data.
AB  - Next-generation sequencing (NGS) has been applied successfully to the field of
      therapeutic antibody discovery, often outperforming conventional screening
      campaigns which tend to identify only the more abundant selective antibody
      sequences. We used NGS to mine the functional nanobody repertoire from a phage
      displayed camelid immune library directed to the recepteur d'origine nantais
      (RON) receptor kinase. Challenges to this application of NGS include accurate
      removal of read errors, correct identification of related sequences, and
      establishing meaningful inclusion criteria for sequences-of-interest. To this
      end, a sequence identity threshold was defined to separate unrelated full-length
      sequence clusters by exploring a large diverse set of publicly available nanobody
      sequences. When combined with majority-rule consensus building, applying this
      elegant clustering approach to the NGS data set revealed a wealth of >5,000
      enriched candidate RON binders. The huge binding potential predicted by the NGS
      approach was explored through a set of randomly selected candidates: 90% were
      confirmed as RON binders, 50% of which functionally blocked RON in an ERK
      phosphorylation assay. Additional validation came from the correct prediction of
      all 35 RON binding nanobodies which were identified by a conventional screening
      campaign of the same immune library. More detailed characterization of a subset
      of RON binders revealed excellent functional potencies and a promising epitope
      diversity. In summary, our approach exposes the functional diversity and quality
      of the outbred camelid heavy chain-only immune response and confirms the power of
      NGS to identify large numbers of promising nanobodies.

PMID- 28443096
TI  - The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In
      Search of a Balanced Immune System.
AB  - Immune cells not only affect tissue homeostasis at the site of inflammation but
      also exert systemic effects contributing to multiple chronic conditions. Recent
      evidence clearly supports an altered T helper 17/regulatory T cell (Th17/Treg)
      balance leading to the development and progression of inflammatory diseases that
      not only affect the gastrointestinal tract but also have whole-body
      manifestations, including insulin resistance. Epigenetic mechanisms are amenable
      to both environmental and circulating factors and contribute to determining the T
      cell landscape. The recently identified participation of the gut microbiota in
      the remodeling of the epigenome of immune cells has triggered a paradigm shift in
      our understanding of the etiology of various inflammatory diseases and opened new
      paths toward therapeutic strategies. In this review, we provide an overview of
      the contribution of the Th17/Treg balance in the development and progression of
      inflammatory bowel diseases and metabolic diseases. We discuss the involvement of
      epigenetic mechanisms in the regulation of T cell function in the particular
      context of dysbiosis. Finally, we examine the potential for nutritional
      interventions affecting the gut microbiota to reshape the T cell epigenome and
      address the inflammatory component of various diseases.

PMID- 28443098
TI  - The Lysine Methyltransferase G9a in Immune Cell Differentiation and Function.
AB  - G9a (KMT1C, EHMT2) is a lysine methyltransferase (KMT) whose primary function is
      to di-methylate lysine 9 of histone H3 (H3K9me2). G9a-dependent H3K9me2 is
      associated with gene silencing and acts primarily through the recruitment of
      H3K9me2-binding proteins that prevent transcriptional activation. Gene repression
      via G9a-dependent H3K9me2 is critically required in embryonic stem (ES) cells for
      the development of cellular lineages by repressing expression of pluripotency
      factors. In the immune system, lymphoid cells such as T cells and innate lymphoid
      cells (ILCs) can differentiate from a naive state into one of several effector
      lineages that require both activating and repressive mechanisms to maintain the
      correct gene expression program. Furthermore, the long-term immunity to re
      infection is mediated by memory T cells, which also require specific gene
      expression and repression to maintain a quiescent state. In this review, we
      examine the molecular machinery of G9a-dependent functions, address the role of
      G9a in lymphoid cell differentiation and function, and identify potential
      functions of T cells and ILCs that may be controlled by G9a. Together, this
      review will highlight the dynamic nature of G9a-dependent H3K9me2 in the immune
      system and shed light on the nature of repressive epigenetic modifications in
      cellular lineage choice.

PMID- 28443100
TI  - (-)-Epigallocatechin Gallate Targets Notch to Attenuate the Inflammatory Response
      in the Immediate Early Stage in Human Macrophages.
AB  - Inflammation plays important roles at different stages of diabetes mellitus,
      tumorigenesis, and cardiovascular diseases. (-)-Epigallocatechin gallate (EGCG)
      can attenuate inflammatory responses effectively. However, the immediate early
      mechanism of EGCG in inflammation remains unclear. Here, we showed that EGCG
      attenuated the inflammatory response in the immediate early stage of EGCG
      treatment by shutting off Notch signaling and that the effect did not involve the
      67-kDa laminin receptor, the common receptor for EGCG. EGCG eliminated mature
      Notch from the cell membrane and the nuclear Notch intercellular domain, the
      active form of Notch, within 2 min by rapid degradation via the proteasome
      pathway. Transcription of the Notch target gene was downregulated simultaneously.
      Knockdown of Notch 1/2 expression by RNA interference impaired the downregulation
      of the inflammatory response elicited by EGCG. Further study showed that EGCG
      inhibited lipopolysaccharide-induced inflammation and turned off Notch signaling
      in human primary macrophages. Taken together, our results show that EGCG targets
      Notch to regulate the inflammatory response in the immediate early stage.

PMID- 28443099
TI  - A Century of Radiation Therapy and Adaptive Immunity.
AB  - The coming of age for immunotherapy (IT) as a genuine treatment option for cancer
      patients through the development of new and effective agents, in particular
      immune checkpoint inhibitors, has led to a huge renaissance of an old idea,
      namely to harness the power of the immune system to that of radiation therapy
      (RT). It is not an overstatement to say that the combination of RT with IT has
      provided a new conceptual platform that has re-energized the field of radiation
      oncology as a whole. One only has to look at the immense rise in sessions at
      professional conferences and in grant applications dealing with this topic to see
      its emergence as a force, while the number of published reviews on the topic is
      staggering. At the time of writing, over 97 clinical trials have been registered
      using checkpoint inhibitors with RT to treat almost 7,000 patients, driven in
      part by strong competition between pharmaceutical products eager to find their
      market niche. Yet, for the most part, this enthusiasm is based on relatively
      limited recent data, and on the clinical success of immune checkpoint inhibitors
      as single agents. A few preclinical studies on RT-IT combinations have added real
      value to our understanding of these complex interactions, but many assumptions
      remain. It seems therefore appropriate to go back in time and pull together what
      actually has been a long history of investigations into radiation and the immune
      system (Figure 1) in an effort to provide context for this interesting
      combination of cancer therapies.

PMID- 28443101
TI  - Characterization of Soybean Genetically Modified for Drought Tolerance in Field
      Conditions.
AB  - Drought is one of the most stressful environmental factor causing yield and
      economic losses in many soybean-producing regions. In the last decades,
      transcription factors (TFs) are being used to develop genetically modified plants
      more tolerant to abiotic stresses. Dehydration responsive element binding (DREB)
      and ABA-responsive element-binding (AREB) TFs were introduced in soybean showing
      improved drought tolerance, under controlled conditions. However, these results
      may not be representative of the way in which plants behave over the entire
      season in the real field situation. Thus, the objectives of this study were to
      analyze agronomical traits and physiological parameters of AtDREB1A (1Ab58),
      AtDREB2CA (1Bb2193), and AtAREB1 (1Ea2939) GM lines under irrigated (IRR) and non
      irrigated (NIRR) conditions in a field experiment, over two crop seasons and
      quantify transgene and drought-responsive genes expression. Results from season
      2013/2014 revealed that line 1Ea2939 showed higher intrinsic water use and leaf
      area index. Lines 1Ab58 and 1Bb2193 showed a similar behavior to wild-type plants
      in relation to chlorophyll content. Oil and protein contents were not affected in
      transgenic lines in NIRR conditions. Lodging, due to plentiful rain, impaired
      yield from the 1Ea2939 line in IRR conditions. qPCR results confirmed the
      expression of the inserted TFs and drought-responsive endogenous genes. No
      differences were identified in the field experiment performed in crop season
      2014/2015, probably due to the optimum rainfall volume during the cycle. These
      field screenings showed promising results for drought tolerance. However,
      additional studies are needed in further crop seasons and other sites to better
      characterize how these plants may outperform the WT under field water deficit.

PMID- 28443102
TI  - Effect of HbDHN1 and HbDHN2 Genes on Abiotic Stress Responses in Arabidopsis.
AB  - Dehydrin is a type of late embryogenesis abundant (LEA) protein. The dehydrin
      genes, HbDHN1 and HbDHN2, in Hevea brasiliensis were previously found to be
      induced at the wounding site of epicormic shoots, with local tissue dehydration
      identified as the key signal for laticifer differentiation. However, the exact
      role of the HbDHNs remains unknown. In this study, HbDHN1 and HbDHN2 expression
      was examined under multiple abiotic stresses; namely, cold, salt, drought,
      wounding, abscisic acid (ABA), ethylene (ET), and jasmonic acid (JA) treatment.
      Although, both HbDHNs were defined as SK2-type dehydrin, they showed different
      cellular localizations. Overexpression of the HbDHNs in Arabidopsis thaliana
      further revealed a significant increase in tolerance to salt, drought and osmotic
      stresses. Increased accumulation of proline and a reduction in electrolyte
      leakage were also observed under salt and drought stress, and a higher water
      content was indicated under osmotic stress. The transgenic plants also showed
      higher activity levels of ascorbate peroxidase (APX), superoxide dismutase (SOD)
      and catalase, and accumulated less hydrogen peroxide (H2O2) and superoxide
      ([Formula: see text]). Given that reactive oxygen species (ROS) are thought to be
      a key signal for laticifer differentiation, these findings suggest that HbDHNs
      act as ROS scavengers, directly or indirectly affecting laticifer
      differentiation. Both HbDHNs therefore influence physiological processes,
      improving plant tolerance to multiple abiotic stresses.

PMID- 28443103
TI  - Genotyping by Sequencing for SNP-Based Linkage Analysis and Identification of
      QTLs Linked to Fruit Quality Traits in Japanese Plum (Prunus salicina Lindl.).
AB  - Marker-assisted selection (MAS) in stone fruit (Prunus species) breeding is
      currently difficult to achieve due to the polygenic nature of the most relevant
      agronomic traits linked to fruit quality. Genotyping by sequencing (GBS),
      however, provides a large quantity of useful data suitable for fine mapping using
      Single Nucleotide Polymorphisms (SNPs) from a reference genome. In this study,
      GBS was used to genotype 272 seedlings of three F1 Japanese plum (Prunus salicina
      Lindl) progenies derived from crossing "98-99" (as a common female parent) with
      "Angeleno," "September King," and "September Queen" as male parents. Raw
      sequences were aligned to the Peach genome v1, and 42,909 filtered SNPs were
      obtained after sequence alignment. In addition, 153 seedlings from the "98-99" *
      "Angeleno" cross were used to develop a genetic map for each parent. A total of
      981 SNPs were mapped (479 for "98-99" and 502 for "Angeleno"), covering a genetic
      distance of 688.8 and 647.03 cM, respectively. Fifty five seedlings from this
      progeny were phenotyped for different fruit quality traits including ripening
      time, fruit weight, fruit shape, chlorophyll index, skin color, flesh color, over
      color, firmness, and soluble solids content in the years 2015 and 2016. Linkage
      based QTL analysis allowed the identification of genomic regions significantly
      associated with ripening time (LG4 of both parents and both phenotyping years),
      fruit skin color (LG3 and LG4 of both parents and both years), chlorophyll
      degradation index (LG3 of both parents in 2015) and fruit weight (LG7 of both
      parents in 2016). These results represent a promising situation for GBS in the
      identification of SNP variants associated to fruit quality traits, potentially
      applicable in breeding programs through MAS, in a highly heterozygous crop
      species such as Japanese plum.

PMID- 28443104
TI  - Genome Wide Identification and Characterization of Apple bHLH Transcription
      Factors and Expression Analysis in Response to Drought and Salt Stress.
AB  - The bHLH (basic helix-loop-helix) transcription factor family is the second
      largest in plants. It occurs in all three eukaryotic kingdoms, and plays
      important roles in regulating growth and development. However, family members
      have not previously been studied in apple. Here, we identified 188 MdbHLH
      proteins in apple "Golden Delicious" (Malus * domestica Borkh.), which could be
      classified into 18 groups. We also investigated the gene structures and 12
      conserved motifs in these MdbHLHs. Coupled with expression analysis and protein
      interaction network prediction, we identified several genes that might be
      responsible for abiotic stress responses. This study provides insight and rich
      resources for subsequent investigations of such proteins in apple.

PMID- 28443105
TI  - Identification of MicroRNA Targets of Capsicum spp. Using MiRTrans-a Trans-Omics
      Approach.
AB  - The microRNA (miRNA) can regulate the transcripts that are involved in eukaryotic
      cell proliferation, differentiation, and metabolism. Especially for plants, our
      understanding of miRNA targets, is still limited. Early attempts of prediction on
      sequence alignments have been plagued by enormous false positives. It is helpful
      to improve target prediction specificity by incorporating the other data sources
      such as the dependency between miRNA and transcript expression or even cleaved
      transcripts by miRNA regulations, which are referred to as trans-omics data. In
      this paper, we developed MiRTrans (Prediction of MiRNA targets by Trans-omics
      data) to explore miRNA targets by incorporating miRNA sequencing, transcriptome
      sequencing, and degradome sequencing. MiRTrans consisted of three major steps.
      First, the target transcripts of miRNAs were predicted by scrutinizing their
      sequence characteristics and collected as an initial potential targets pool.
      Second, false positive targets were eliminated if the expression of miRNA and its
      targets were weakly correlated by lasso regression. Third, degradome sequencing
      was utilized to capture the miRNA targets by examining the cleaved transcripts
      that regulated by miRNAs. Finally, the predicted targets from the second and
      third step were combined by Fisher's combination test. MiRTrans was applied to
      identify the miRNA targets for Capsicum spp. (i.e., pepper). It can generate more
      functional miRNA targets than sequence-based predictions by evaluating functional
      enrichment. MiRTrans identified 58 miRNA-transcript pairs with high confidence
      from 18 miRNA families conserved in eudicots. Most of these targets were
      transcription factors; this lent support to the role of miRNA as key regulator in
      pepper. To our best knowledge, this work is the first attempt to investigate the
      miRNA targets of pepper, as well as their regulatory networks. Surprisingly, only
      a small proportion of miRNA-transcript pairs were shared between degradome
      sequencing and expression dependency predictions, suggesting that miRNA targets
      predicted by a single technology alone may be prone to report false negatives.

PMID- 28443106
TI  - Over-expression of EjLFY-1 Leads to an Early Flowering Habit in Strawberry
      (Fragaria * ananassa) and Its Asexual Progeny.
AB  - As a master regulator involved in flower development, LEAFY-like gene has been
      demonstrated to play a key role in the flowering process regulation of
      angiosperms. Expression analysis of EjLFY-1, a LEAFY (LFY) homolog of loquat
      (Eriobotrya japonica Lindl.), indicated its participation in the regulation of
      flowering in loquat. To verify its function and potential value in the genetic
      engineering to shorten the juvenile phase, ectopic expression of EjLFY-1 in
      strawberry (Fragaria * ananassa) was achieved using Agrobacterium-mediated gene
      transfer of a plant expression vector with the loquat EjLFY-1 gene driven by the
      CaMV 35S promoter. Totally 59 plantlets were verified to be the transformants.
      The presence, expression and integration of EjLFY-1 in the transformants were
      assessed by PCR, quantitative real-time PCR and Southern blot, respectively.
      Constitutive expression of EjLFY-1 in strawberry accelerated the flowering
      process in strawberry with the shorten necessary period for flowering induction,
      development of flower and fruit set. While vegetative growth habits of the
      transformants in the first cropping season were consistent with the WT ones.
      Meanwhile, both the flowers and fruits of the transformants were also as same as
      those of the WT ones. Furthermore, the early-flowering habit was maintained in
      their asexual progeny, the runner plants. While with continuous asexual
      propagation, the clones showed a more strengthen early-flowering phenotype, such
      as the reduced vegetative growth and the abnormal floral organs in individual
      plantlets. These results demonstrated the function of this gene and at the same
      time provided us new insights into the utilization potential of such genes in the
      genetic engineering of perennial fruits.

PMID- 28443107
TI  - Virus-Based MicroRNA Silencing and Overexpressing in Common Wheat (Triticum
      aestivum L.).
AB  - MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that arise
      from large RNA precursors with a stem-loop structure and play important roles in
      plant development and responses to environmental stress. Although a hundred and
      nineteen wheat miRNAs have been identified and registered in the miRBase (Release
      21.0, June, 2014; http://www.mirbase.org), the functional characterization of
      these miRNAs in wheat growth and development is lagging due to lack of effective
      techniques to investigate endogenous miRNA functions in wheat. Here we report
      barley stripe mosaic virus(BSMV)-based miRNA overexpression and silence systems
      that can be applied to study miRNA functions in wheat. By utilizing the BSMV
      system, we successfully knocked down endogenous miR156 and miR166 levels and over
      expressed endogenous miR156 and artificial miRNA against phytoene desaturase gene
      PDS (amiR-PDS) in wheat. amiR-PDS expression caused a great reduction in
      endogenous mRNA abundance of PDS gene in wheat plant, leading to leaf obviously
      photobleaching. miR156 silencing led to a great increase in the mRNA level of its
      target gene SPL2, resulting in a leaf-curl phenotype in wheat seedlings. In
      contrast, overexpression of miR156 led to a significant reduction in the mRNA
      level of SPL2 in wheat seedlings, resulting in serious delay of the vegetative
      phase transitions as well as booting and flowering in wheat. These confirmed that
      miR156 regulates wheat development and booting time through SPL genes. In
      summary, the BSMV-based miRNA overexpression and silence systems have
      extraordinary potential not only for functional study of protein-encoding genes
      but also for miRNA genes in wheat.

PMID- 28443108
TI  - The Kinase Activity of Calcineurin B-like Interacting Protein Kinase 26 (CIPK26)
      Influences Its Own Stability and that of the ABA-regulated Ubiquitin Ligase, Keep
      on Going (KEG).
AB  - The Really Interesting New Gene (RING)-type E3 ligase, Keep on Going (KEG) plays
      a critical role in Arabidopsis growth after germination and the connections
      between KEG and hormone signaling pathways are expanding. With regards to
      abscisic acid (ABA) signaling, KEG targets ABA-responsive transcription factors
      abscisic acid insensitive 5, ABF1 and ABF3 for ubiquitination and subsequent
      degradation through the 26S proteasome. Regulation of E3 ligases through self
      ubiquitination is common to RING-type E3 ligases and ABA promotes KEG self
      ubiquitination and degradation. ABA-mediated degradation of KEG is
      phosphorylation-dependent; however, upstream signaling proteins that may regulate
      KEG stability have not been characterized. In this report, we show that CBL
      Interacting Protein Kinase (CIPK) 26 can phosphorylate KEG in vitro. Using both
      in vitro and in planta degradation assays we provide evidence which suggests that
      the kinase activity of CIPK26 promotes the degradation of KEG. Furthermore, we
      found that the kinase activity of CIPK26 also influences its own stability; a
      constitutively active version is more stable than a wild type or a kinase dead
      version. Our results suggest a reciprocal regulation model wherein an activated
      and stable CIPK26 phosphorylates KEG to promote degradation of the E3.

PMID- 28443109
TI  - Novel Alleles of Phosphorus-Starvation Tolerance 1 Gene (PSTOL1) from Oryza
      rufipogon Confers High Phosphorus Uptake Efficiency.
AB  - Limited phosphorus availability in the soil is one of the major constraints to
      the growth and productivity of rice across Asian, African and South American
      countries, where 50% of the rice is grown under rain-fed systems on poor and
      problematic soils. With an aim to determine novel alleles for enhanced phosphorus
      uptake efficiency in wild species germplasm of rice Oryza rufipogon, we
      investigated phosphorus uptake1 (Pup1) locus with 11 previously reported SSR
      markers and sequence characterized the phosphorus-starvation tolerance 1 (PSTOL1)
      gene. In the present study, we screened 182 accessions of O. rufipogon along with
      Vandana as a positive control with SSR markers. From the analysis, it was
      inferred that all of the O. rufipogon accessions undertaken in this study had an
      insertion of 90 kb region, including Pup1-K46, a diagnostic marker for PSTOL1,
      however, it was absent among O. sativa cv. PR114, PR121, and PR122. The complete
      PSTOL1 gene was also sequenced in 67 representative accessions of O. rufipogon
      and Vandana as a positive control. From comparative sequence analysis, 53
      mutations (52 SNPs and 1 nonsense mutation) were found in the PSTOL1 coding
      region, of which 28 were missense mutations and 10 corresponded to changes in the
      amino acid polarity. These 53 mutations correspond to 17 haplotypes, of these 6
      were shared and 11 were scored only once. A major shared haplotype was observed
      among 44 accessions of O. rufipogon along with Vandana and Kasalath. Out of 17
      haplotypes, accessions representing 8 haplotypes were grown under the phosphorus
      deficient conditions in hydroponics for 60 days. Significant differences were
      observed in the root length and weight among all the genotypes when grown under
      phosphorus deficiency conditions as compared to the phosphorus sufficient
      conditions. The O. rufipogon accession IRGC 106506 from Laos performed
      significantly better, with 2.5 times higher root weight and phosphorus content as
      compared to the positive control Vandana. In terms of phosphorus uptake
      efficiency, the O. rufipogon accessions IRGC 104639, 104712, and 105569 also
      showed nearly two times higher phosphorus content than Vandana. Thus, these O.
      rufipogon accessions could be used as the potential donor for improving
      phosphorus uptake efficiency of elite rice cultivars.

PMID- 28443110
TI  - Expression Profiling of Castanea Genes during Resistant and Susceptible
      Interactions with the Oomycete Pathogen Phytophthora cinnamomi Reveal Possible
      Mechanisms of Immunity.
AB  - The most dangerous pathogen affecting the production of chestnuts is Phytophthora
      cinnamomi a hemibiotrophic that causes root rot, also known as ink disease.
      Little information has been acquired in chestnut on the molecular defense
      strategies against this pathogen. The expression of eight candidate genes
      potentially involved in the defense to P. cinnamomi was quantified by digital PCR
      in Castanea genotypes showing different susceptibility to the pathogen. Seven of
      the eight candidate genes displayed differentially expressed levels depending on
      genotype and time-point after inoculation. Cast_Gnk2-like revealed to be the most
      expressed gene across all experiments and the one that best discriminates between
      susceptible and resistant genotypes. Our data suggest that the pre-formed
      defenses are crucial for the resistance of C. crenata to P. cinnamomi. A lower
      and delayed expression of the eight studied genes was found in the susceptible
      Castanea sativa, which may be related with the establishment and spread of the
      disease in this species. A working model integrating the obtained results is
      presented.

PMID- 28443111
TI  - Subcellular Compartmentalization and Chemical Forms of Lead Participate in Lead
      Tolerance of Robinia pseudoacacia L. with Funneliformis mosseae.
AB  - The effect of arbuscular mycorrhizal fungus on the subcellular
      compartmentalization and chemical forms of lead (Pb) in Pb tolerance plants was
      assessed in a pot experiment in greenhouse conditions. We measured root
      colonization, plant growth, photosynthesis, subcellular compartmentalization and
      chemical forms of Pb in black locust (Robinia pseudoacacia L.) seedlings
      inoculated with Funneliformis mosseae isolate (BGC XJ01A) under a range of Pb
      treatments (0, 90, 900, and 3000 mg Pb kg-1 soil). The majority of Pb was
      retained in the roots of R. pseudoacacia under Pb stress, with a significantly
      higher retention in the inoculated seedlings. F. mosseae inoculation
      significantly increased the proportion of Pb in the cell wall and soluble
      fractions and decreased the proportion of Pb in the organelle fraction of roots,
      stems, and leaves, with the largest proportion of Pb segregated in the cell wall
      fraction. F. mosseae inoculation increased the proportion of inactive Pb
      (especially pectate- and protein-integrated Pb and Pb phosphate) and reduced the
      proportion of water-soluble Pb in the roots, stems, and leaves. The subcellular
      compartmentalization of Pb in different chemical forms was highly correlated with
      improved plant biomass, height, and photosynthesis in the inoculated seedlings.
      This study indicates that F. mosseae could improve Pb tolerance in R.
      pseudoacacia seedlings growing in Pb polluted soils.

PMID- 28443112
TI  - Transcriptome-Guided Mining of Genes Involved in Crocin Biosynthesis.
AB  - Gardenia jasminoides is used in traditional Chinese medicine and has drawn
      attention as a rich source of crocin, a compound with reported activity against
      various cancers, depression and cardiovascular disease. However, genetic
      information on the crocin biosynthetic pathway of G. jasminoides is scarce. In
      this study, we performed a transcriptome analysis of the leaves, green fruits,
      and red fruits of G. jasminoides to identify and predict the genes that encode
      key enzymes responsible for crocin production, compared with Crocus sativus.
      Twenty-seven putative pathway genes were specifically expressed in the fruits,
      consistent with the distribution of crocin in G. jasminoides. Twenty-four of
      these genes were reported for the first time, and a novel CCD4a gene was
      predicted that encodes carotenoid cleavage dioxygenase leading to crocin
      synthesis, in contrast to CCD2 of C. sativus. In addition, 6 other candidate
      genes (ALDH12, ALDH14, UGT94U1, UGT86D1, UGT71H4, and UGT85K18) were predicted to
      be involved in crocin biosynthesis following phylogenetic analysis and different
      gene expression profiles. Identifying the genes that encode key enzymes should
      help elucidate the crocin biosynthesis pathway.

PMID- 28443113
TI  - Barcode System for Genetic Identification of Soybean [Glycine max (L.) Merrill]
      Cultivars Using InDel Markers Specific to Dense Variation Blocks.
AB  - For genetic identification of soybean [Glycine max (L.) Merrill] cultivars,
      insertions/deletions (InDel) markers have been preferred currently because they
      are easy to use, co-dominant and relatively abundant. Despite their biological
      importance, the investigation of InDels with proven quality and reproducibility
      has been limited. In this study, we described soybean barcode system approach
      based on InDel makers, each of which is specific to a dense variation block (dVB)
      with non-random recombination due to many variations. Firstly, 2,274 VBs were
      mined by analyzing whole genome data in six soybean cultivars (Backun, Sinpaldal
      2, Shingi, Daepoong, Hwangkeum, and Williams 82) for transferability to dVB
      specific InDel markers. Secondly, 73,327 putative InDels in the dVB regions were
      identified for the development of soybean barcode system. Among them, 202 dVB
      specific InDels from all soybean cultivars were selected by gel electrophoresis,
      which were converted as 2D barcode types according to comparing amplicon
      polymorphisms in the five cultivars to the reference cultivar. Finally, the
      polymorphism of the markers were assessed in 147 soybean cultivars, and the
      soybean barcode system that allows a clear distinction among soybean cultivars is
      also detailed. In addition, the changing of the dVBs in a chromosomal level can
      be quickly identified due to investigation of the reshuffling pattern of the
      soybean cultivars with 27 maker sets. Especially, a backcross-inbred offspring,
      "Singang" and a recurrent parent, "Sowon" were identified by using the 27 InDel
      markers. These results indicate that the soybean barcode system enables not only
      the minimal use of molecular markers but also comparing the data from different
      sources due to no need of exploiting allele binning in new varieties.

PMID- 28443114
TI  - TaDIR1-2, a Wheat Ortholog of Lipid Transfer Protein AtDIR1 Contributes to
      Negative Regulation of Wheat Resistance against Puccinia striiformis f. sp.
      tritici.
AB  - Very few LTPs have been shown to act through plasma membrane receptors or to be
      involved in the hypersensitive response (HR). DIR1, a new type of plant LTP
      interacts with lipids in vitro, moves to distant tissues during systemic acquired
      resistance (SAR) and therefore is thought to be involved in long-distance
      signaling during SAR. However, the exact functions of DIR1 orthologs in cereal
      species under biotic and abiotic stresses have not been thoroughly defined. In
      this study, a novel wheat ortholog of the DIR1 gene, TaDIR1-2, was isolated from
      Suwon11, a Chinese cultivar of wheat and functionally characterized. Phylogenetic
      analysis indicated that TaDIR1-2 is clustered within the nsLTP-Type II group and
      shows a closer relationship with DIR1 orthologs from monocots than from eudicots.
      TaDIR1-2 was localized in the cytoplasm and the cell membrane of wheat mesophyll
      protoplast. Transcription of TaDIR1-2 was detected in wheat roots, stems and
      leaves. TaDIR1-2 transcript was significantly induced during the compatible
      interaction of wheat with the stripe rust pathogen, Puccinia striiformis f. sp.
      tritici (Pst). Treatments with salicylic acid (SA) and low temperature
      significantly up-regulated the expression of TaDIR1-2. Transient overexpression
      of TaDIR1-2 did not induce cell death or suppress Bax-induced cell death in
      tobacco leaves. Knocking down the expression of TaDIR1-2 through virus-induced
      gene silencing increased wheat resistance to Pst accompanied by HR, increased
      accumulation of H2O2 and SA, increased expression of TaPR1, TaPR2, TaPAL, and
      TaNOX, and decreased expression of two reactive oxygen species (ROS) scavenging
      genes TaCAT and TaSOD. Our results suggest that TaDIR1-2 acts as a negative
      regulator in wheat resistance to Pst by modulating ROS and/or SA-induced
      signaling.

PMID- 28443115
TI  - Cytosolic Glyceraldehyde-3-Phosphate Dehydrogenase Is Phosphorylated during Seed
      Development.
AB  - Cytosolic glyceraldehyde-3-phosphate dehydrogenase (NAD-GAPDH) is involved in a
      critical energetic step of glycolysis and also has many important functions
      besides its enzymatic activity. The recombinant wheat NAD-GAPDH was
      phosphorylated in vitro at Ser205 by a SNF1-Related protein kinase 1 (SnRK1) from
      wheat heterotrophic (but not from photosynthetic) tissues. The S205D mutant
      enzyme (mimicking the phosphorylated form) exhibited a significant decrease in
      activity but similar affinity toward substrates. Immunodetection and activity
      assays showed that NAD-GAPDH is phosphorylated in vivo, the enzyme depicting
      different activity, abundance and phosphorylation profiles during development of
      seeds that mainly accumulate starch (wheat) or lipids (castor oil seed). NAD
      GAPDH activity gradually increases along wheat seed development, but protein
      levels and phosphorylation status exhibited slight changes. Conversely, in castor
      oil seed, the activity slightly increased and total protein levels do not
      significantly change in the first half of seed development but both abruptly
      decreased in the second part of development, when triacylglycerol synthesis and
      storage begin. Interestingly, phospho-NAD-GAPDH levels reached a maximum when the
      seed switch their metabolism to mainly support synthesis and accumulation of
      carbon reserves. After this point the castor oil seed NAD-GAPDH protein levels
      and activity highly decreased, and the protein stability assays showed that the
      protein would be degraded by the proteasome. The results presented herein suggest
      that phosphorylation of NAD-GAPDH during seed development would have impact on
      the partitioning of triose-phosphate between different metabolic pathways and
      cell compartments to support the specific carbon, energy and reducing equivalent
      demands during synthesis of storage products.

PMID- 28443116
TI  - Comparative Analysis of Phosphoproteome Remodeling After Short Term Water Stress
      and ABA Treatments versus Longer Term Water Stress Acclimation.
AB  - Several studies have used short term dehydration, osmotic stress or Abscisic Acid
      (ABA) treatments to identify the initial protein phosphorylation
      dephosphorylation responses to drought and low water potential or ABA treatments.
      However, longer term drought acclimation leads to altered expression of many
      kinases and phosphatases suggesting that it may also produce unique changes in
      phosphoproteome composition. To get a better overview of the state of drought
      related phosphoproteomics and investigate this question of short versus longer
      term phosphoproteome regulation, we compared three Arabidopsis thaliana studies
      analyzing short term phosphoproteome changes to recent data from our laboratory
      analyzing phosphoproteome changes after a longer drought acclimation treatment.
      There was very little overlap of phosphoproteins with putative stress-induced
      phosphorylation or dephosphorylation among these studies. While some of this is
      due to technical limitations and limited coverage of the phosphoproteome achieved
      by each study, biological differences and the type of stress treatment used also
      play a role. This comparative analysis emphasized how both short and long term
      analysis of physiologically relevant stress treatments, as well as validation of
      phosphoproteomic data, will be needed to move past just scratching the surface of
      the stress phosphoproteome. In drought acclimation experiments, distinguishing
      between changes in protein abundance versus phosphorylation stoichiometry is a
      key challenge. We discuss initial work in using Arabidopsis seedling transient
      expression combined with Phos-tag gel analysis as a way to validate drought
      induced phosphorylation-dephosphorylation of candidate proteins.

PMID- 28443118
TI  - The Absence of the Arabidopsis Chaperone Complex CAF-1 Produces Mitotic
      Chromosome Abnormalities and Changes in the Expression Profiles of Genes Involved
      in DNA Repair.
AB  - Chromatin Assembly Factor 1 (CAF-1) is an evolutionary conserved heterotrimeric
      chaperone complex that facilitates the incorporation of histones H3 and H4 onto
      newly synthesized DNA. We demonstrate here that the mutant deficient for the
      large subunit of the complex, fas1-4, and in minor extent, the mutant deficient
      for the middle subunit, fas2-1, display chromosome abnormalities throughout
      Arabidopsis mitosis. Among them, we observed multicentromeric chromosomes at
      metaphase, and chromatid bridges and acentric fragments at anaphase-telophase.
      45S rDNA and telomeric sequences were frequently involved in bridges and
      fragments. Gene expression analysis by real-time qPCR has revealed that several
      genes related to homologous recombination (HR) and alternative non-homologous end
      joining (aNHEJ) are overexpressed in fas1-4. These results concur with previous
      studies which have indicated that HR may be involved in the progressive loss of
      45S rDNA and telomeres displayed by fas mutants. However, increased expression of
      PARP1, PARP2, and LIG6 in fas1-4, and the phenotype shown by the double mutant
      fas1 rad51 suggest that aNHEJ should also be responsible for the chromosomal
      aberrations observed. The activity of different DNA repair pathways in absence of
      CAF-1 is discussed.

PMID- 28443117
TI  - Seed Biology Updates - Highlights and New Discoveries in Seed Dormancy and
      Germination Research.
AB  - An understanding of the biology of seeds has been greatly advanced in recent
      years. The progresses, particularly in the field of seed dormancy and germination
      research, have been made at a remarkable speed. Some of the possible epigenetic
      mechanisms, including an involvement of non-coding RNA, which were predicted for
      DELAY OF GERMINATION1 just a few years ago, have now been demonstrated with
      strong molecular and genetic evidence. Imprinting, or parent-of-origin-specific
      gene silencing/expression, which was characterized particularly for developing
      seeds, was also found in imbibed seeds and suggested for dormancy mechanisms.
      Hormone biology in seeds, which is the most advanced and almost a traditional
      area of seed research, also presents a new dimension. Upstream regulators of
      hormone metabolism and hormone transporters, such as abscisic acid and
      gibberellin influx/efflux carriers, have been identified. Characterization of the
      novel posttranslational modification pathways, including the N-end rule and S
      nitrosylation pathways, which play a critical role in turnover of the major
      hormone signal transduction proteins, also expanded our knowledge about the
      complexity of hormone signaling in seeds. These progresses made at the molecular
      level are significant steps toward a better understanding of how seeds translate
      soil and other environmental signals into their internal hormone biology and make
      an important decision to stay dormant or commence with germination.

PMID- 28443119
TI  - Parsing the Regulatory Network between Small RNAs and Target Genes in Ethylene
      Pathway in Tomato.
AB  - Small RNAs are a class of short non-coding endogenous RNAs that play essential
      roles in many biological processes. Recent studies have reported that microRNAs
      (miRNAs) are also involved in ethylene signaling in plants. LeERF1 is one of the
      ethylene response factors (ERFs) in tomato that locates in the downstream of
      ethylene signal transduction pathway. To elucidate the intricate regulatory roles
      of small RNAs in ethylene signaling pathway in tomato, the deep sequencing and
      bioinformatics methods were combined to decipher the small RNAs landscape in wild
      and sense-/antisense-LeERF1 transgenic tomato fruits. Except for the known
      miRNAs, 36 putative novel miRNAs, 6 trans-acting short interfering RNAs (ta
      siRNAs), and 958 natural antisense small interfering RNAs (nat-siRNAs) were also
      found in our results, which enriched the tomato small RNAs repository. Among
      these small RNAs, 9 miRNAs, and 12 nat-siRNAs were differentially expressed
      between the wild and transgenic tomato fruits significantly. A large amount of
      target genes of the small RNAs were identified and some of them were involved in
      ethylene pathway, including AP2 TFs, auxin response factors, F-box proteins, ERF
      TFs, APETALA2-like protein, and MADS-box TFs. Degradome sequencing further
      confirmed the targets of miRNAs and six novel targets were also discovered.
      Furthermore, a regulatory model which reveals the regulation relationships
      between the small RNAs and their targets involved in ethylene signaling was set
      up. This work provides basic information for further investigation of the
      function of small RNAs in ethylene pathway and fruit ripening.

PMID- 28443120
TI  - Dissecting Low Atmospheric Pressure Stress: Transcriptome Responses to the
      Components of Hypobaria in Arabidopsis.
AB  - Controlled hypobaria presents biology with an environment that is never
      encountered in terrestrial ecology, yet the apparent components of hypobaria are
      stresses typical of terrestrial ecosystems. High altitude, for example, presents
      terrestrial hypobaria always with hypoxia as a component stress, since the
      relative partial pressure of O2 is constant in the atmosphere. Laboratory
      controlled hypobaria, however, allows the dissection of pressure effects away
      from the effects typically associated with altitude, in particular hypoxia, as
      the partial pressure of O2 can be varied. In this study, whole transcriptomes of
      plants grown in ambient (97 kPa/pO2 = 21 kPa) atmospheric conditions were
      compared to those of plants transferred to five different atmospheres of varying
      pressure and oxygen composition for 24 h: 50 kPa/pO2 = 10 kPa, 25 kPa/pO2 = 5
      kPa, 50 kPa/pO2 = 21 kPa, 25 kPa/pO2 = 21 kPa, or 97 kPa/pO2 = 5 kPa. The plants
      exposed to these environments were 10 day old Arabidopsis seedlings grown
      vertically on hydrated nutrient plates. In addition, 5 day old plants were also
      exposed for 24 h to the 50 kPa and ambient environments to evaluate age-dependent
      responses. The gene expression profiles from roots and shoots showed that the
      hypobaric response contained more complex gene regulation than simple hypoxia,
      and that adding back oxygen to normoxic conditions did not completely alleviate
      gene expression changes in hypobaric responses.

PMID- 28443121
TI  - Hormonal and Nutritional Features in Contrasting Rootstock-mediated Tomato Growth
      under Low-phosphorus Nutrition.
AB  - Grafting provides a tool aimed to increase low-P stress tolerance of crops,
      however, little is known about the mechanism (s) by which rootstocks can confer
      resistance to P deprivation. In this study, 4 contrasting groups of rootstocks
      from different genetic backgrounds (Solanum lycopersicum var. cerasiforme and
      introgression and recombinant inbred lines derived from the wild relatives S.
      pennellii and S. pimpinellifolium) were grafted to a commercial F1 hybrid scion
      and cultivated under control (1 mM, c) and P deficient (0.1 mM, p) conditions for
      30 days, to analyze rootstocks-mediated traits that impart low (L, low shoot dry
      weight, SDW) or high (H, high SDW) vigor. Xylem sap ionic and hormonal anlyses
      leaf nutritional status suggested that some physiological traits can explain
      rootstocks impacts on shoot growth. Although xylem P concentration increased with
      root biomass under both growing conditions, shoot biomass under low-P was
      explained by neither changes in root growth nor P transport and assimilation.
      Indeed, decreased root P export only explained the sensitivity of the HcLp
      rootstocks, while leaf P status was similarly affected in all graft combinations.
      Interestingly, most of the nutrients analyzed in the xylem sap correlated with
      root biomass under standard fertilization but only Ca was consistently related to
      shoot biomass under both control and low-P, suggesting an important role for this
      nutrient in rootstock-mediated vigor. Moreover, foliar Ca, S, and Mn
      concentrations were (i) specifically correlated with shoot growth under low-P and
      (ii) positively and negatively associated to the root-to-shoot transport of the
      cytokinin trans-zeatin (t-Z) and the ethylene precursor 1-aminocyclopropane-1
      carboxylic acid (ACC), respectively. Indeed, those hormones seem to play an
      antagonistic positive (t-Z) and negative (ACC) role in the rootstock-mediated
      regulation of shoot growth in response to P nutrition. The use of Hp-type
      rootstocks seems to enhance P use efficiency of a commercial scion variety,
      therefore could potentially be used for increasing yield and agronomic stability
      under low P availability.

PMID- 28443123
TI  - Firmness at Harvest Impacts Postharvest Fruit Softening and Internal Browning
      Development in Mechanically Damaged and Non-damaged Highbush Blueberries
      (Vaccinium corymbosum L.).
AB  - Fresh blueberries are very susceptible to mechanical damage, which limits
      postharvest life and firmness. Softening and susceptibility of cultivars "Duke"
      and "Brigitta" to developing internal browning (IB) after mechanical impact and
      subsequent storage was evaluated during a 2-year study (2011/2012, 2012/2013). On
      each season fruit were carefully hand-picked, segregated into soft (<1.60 N),
      medium (1.61-1.80 N), and firm (1.81-2.00 N) categories, and then either were
      dropped (32 cm) onto a hard plastic surface or remained non-dropped. All fruit
      were kept under refrigerated storage (0 degrees C and 85-88% relative humidity)
      to assess firmness loss and IB after 7, 14, 21, 28, and 35 days. In general,
      regardless of cultivar or season, high variability in fruit firmness was observed
      within each commercial harvest, and significant differences in IB and softening
      rates were found. "Duke" exhibited high softening rates, as well as high and
      significant r2 between firmness and IB, but little differences for dropped vs.
      non-dropped fruit. "Brigitta," having lesser firmness rates, exhibited almost no
      relationships between firmness and IB (especially for non-dropped fruit), but
      marked differences between dropping treatments. Firmness loss and IB development
      were related to firmness at harvest, soft and firm fruit being the most and least
      damaged, respectively. Soft fruit were characterized by greater IB development
      during storage along with high soluble solids/acid ratio, which could be used
      together with firmness to estimate harvest date and storage potential of fruit.
      Results of this work suggest that the differences in fruit quality traits at
      harvest could be related to the time that fruit stay on the plant after turning
      blue, soft fruit being more advanced in maturity. Finally, the observed
      differences between segregated categories reinforce the importance of analyzing
      fruit condition for each sorted group separately.

PMID- 28443124
TI  - Fine Mapping of a Resistance Gene RpsHN that Controls Phytophthora sojae Using
      Recombinant Inbred Lines and Secondary Populations.
AB  - Phytophthora root rot (PRR), caused by Phytophthora sojae, has negative effects
      on soybean yield in China and can be controlled by identifying germplasm
      resources with resistance genes. In this study, the resistance locus RpsHN in the
      soybean line Meng8206 was mapped using two mapping populations. Initial mapping
      was realized using two recombinant inbred line (RIL) populations and included 103
      F6:8 RILs derived from a cross of Meng8206 * Linhedafenqing, including 2600 bin
      markers, and 130 F6:8 RILs derived from a cross of Meng8206 * Zhengyang148,
      including 2267 bin markers. Subsequently, a 159 F2:3 secondary population derived
      from a cross of Meng8206 * Linmeng6-46, were used to fine map this locus using
      SSR markers. Finally, the resistance locus from Meng8206 was fine mapped to a
      278.7 kb genomic region flanked by SSR markers SSRSOYN-25 and SSRSOYN-44 at a
      genetic distance of 1.6 and 1.0 cM on chromosome 3 (Chr. 03). Real-time RT-PCR
      analysis of the possible candidate genes showed that three genes (Glyma.03g04260,
      Glyma.03g04300, and Glyma.03g04340) are likely involved in PRR resistance. These
      results will serve as a basis for cloning, transferring of resistant genes and
      breeding of P. sojae-resistant soybean cultivars through marker-assisted
      selection.

PMID- 28443122
TI  - Membrane Proteomics of Arabidopsis Glucosinolate Mutants cyp79B2/B3 and myb28/29.
AB  - Glucosinolates (Gls) constitute a major group of natural metabolites represented
      by three major classes (aliphatic, indolic and aromatic) of more than 120
      chemical structures. In our previous work, soluble proteins and metabolites in
      Arabidopsis mutants deficient of aliphatic (myb28/29) and indolic Gls (cyp79B2B3)
      were analyzed. Here we focus on investigating the changes at the level of
      membrane proteins in these mutants. Our LC/MS-MS analyses of tandem mass tag
      (TMT) labeled peptides derived from the cyp79B2/B3 and myb28/29 relative to wild
      type resulted in the identification of 4,673 proteins, from which 2,171 are
      membrane proteins. Fold changes and statistical analysis showed 64 increased and
      74 decreased in cyp79B2/B3, while 28 increased and 17 decreased in myb28/29. As
      to the shared protein changes between the mutants, one protein was increased and
      eight were decreased. Bioinformatics analysis of the changed proteins led to the
      discovery of three cytochromes in glucosinolate molecular network (GMN):
      cytochrome P450 86A7 (At1g63710), cytochrome P450 71B26 (At3g26290), and probable
      cytochrome c (At1g22840). CYP86A7 and CYP71B26 may play a role in hydroxyl
      indolic Gls production. In addition, flavone 3'-O-methyltransferase 1 represents
      an interesting finding as it is likely to participate in the methylation process
      of the hydroxyl-indolic Gls to form methoxy-indolic Gls. The analysis also
      revealed additional new nodes in the GMN related to stress and defense activity,
      transport, photosynthesis, and translation processes. Gene expression and protein
      levels were found to be correlated in the cyp79B2/B3, but not in the myb28/29.

PMID- 28443125
TI  - Viral Vectors for Plant Genome Engineering.
AB  - Recent advances in genome engineering (GE) has made it possible to precisely
      alter DNA sequences in plant cells, providing specifically engineered plants with
      traits of interest. Gene targeting efficiency depends on the delivery-method of
      both sequence-specific nucleases and repair templates, to plant cells. Typically,
      this is achieved using Agrobacterium mediated transformation or particle
      bombardment, both of which transform only a subset of cells in treated tissues.
      The alternate in planta approaches, stably integrating nuclease-encoding
      cassettes and repair templates into the plant genome, are time consuming,
      expensive and require extra regulations. More efficient GE reagents delivery
      methods are clearly needed if GE is to become routine, especially in economically
      important crops that are difficult to transform. Recently, autonomously
      replicating virus-based vectors have been demonstrated as efficient means of
      delivering GE reagents in plants. Both DNA viruses (Bean yellow dwarf virus,
      Wheat dwarf virus and Cabbage leaf curl virus) and RNA virus (Tobacco rattle
      virus) have demonstrated efficient gene targeting frequencies in model plants
      (Nicotiana benthamiana) and crops (potato, tomato, rice, and wheat). Here we
      discuss the recent advances using viral vectors for plant genome engineering, the
      current limitations and future directions.

PMID- 28443126
TI  - Genome-wide Identification, Characterization, and Expression Analysis of PHT1
      Phosphate Transporters in Wheat.
AB  - The PHT1 family of phosphate (Pi) transporters mediates phosphorus (P) uptake and
      re-mobilization in plants. A genome-wide sequence analysis of PHT1 genes in wheat
      (Triticum aestivum) was conducted, and their expression locations and responses
      to P availability were further investigated. We cloned 21 TaPHT1 genes from the
      homologous alleles at TaPHT1.1 to 1.10 through screening a BAC library and
      amplifying genomic sequences. The TaPHT1 transporters were clustered into five
      branches in the phylogenetic tree of PHT1 proteins, and the TaPHT1 genes from a
      given branch shared high similarities in sequences, expression locations, and
      responses to P availability. The seven tested PHT1 genes all showed Pi-transport
      activity in yeast (Saccharomyces cerevisiae) cells grown under both low Pi and
      high Pi conditions. The expression of TaPHT1.1/1.9, 1.2, and 1.10 were root
      specific. The expression of these TaPHT1 genes at flowering positively correlated
      with P uptake after stem elongation across three P application rates and two
      wheat varieties in a field experiment. Therefore, modification of PHT1 expression
      may improve P use efficiency in a broad regime of P availability.

PMID- 28443128
TI  - Physiological and Molecular Characterization of Hydroxyphenylpyruvate Dioxygenase
      (HPPD)-inhibitor Resistance in Palmer Amaranth (Amaranthus palmeri S.Wats.).
AB  - Herbicides that inhibit hydroxyphenylpyruvate dioxygenase (HPPD) such as
      mesotrione are widely used to control a broad spectrum of weeds in agriculture.
      Amaranthus palmeri is an economically troublesome weed throughout the United
      States. The first case of evolution of resistance to HPPD-inhibiting herbicides
      in A. palmeri was documented in Kansas (KS) and later in Nebraska (NE). The
      objective of this study was to investigate the mechansim of HPPD-inhibitor
      (mesotrione) resistance in A. palmeri. Dose response analysis revealed that this
      population (KSR) was 10-18 times more resistant than their sensitive counterparts
      (MSS or KSS). Absorbtion and translocation analysis of [14C] mesotrione suggested
      that these mechanisms were not involved in the resistance in A. palmeri.
      Importantly, mesotrione (>90%) was detoxified markedly faster in the resistant
      populations (KSR and NER), within 24 hours after treatment (HAT) compared to
      sensitive plants (MSS, KSS, or NER). However, at 48 HAT all populations
      metabolized the mesotrione, suggesting additional factors may contribute to this
      resistance. Further evaluation of mesotrione-resistant A. palmeri did not reveal
      any specific resistance-conferring mutations nor amplification of HPPD gene, the
      molecular target of mesotrione. However, the resistant populations showed 4- to
      12-fold increase in HPPD gene expression. This increase in HPPD transcript levels
      was accompanied by increased HPPD protein expression. The significant aspects of
      this research include: the mesotrione resistance in A. palmeri is conferred
      primarily by rapid detoxification (non-target-site based) of mesotrione;
      additionally, increased HPPD gene expression (target-site based) also contributes
      to the resistance mechanism in the evolution of herbicide resistance in this
      naturally occurring weed species.

PMID- 28443127
TI  - Transcriptome Analysis of a Female-sterile Mutant (fsm) in Chinese Cabbage
      (Brassica campestris ssp. pekinensis).
AB  - Female-sterile mutants are ideal materials for studying pistil development in
      plants. Here, we identified a female-sterile mutant fsm in Chinese cabbage. This
      mutant, which exhibited stable inheritance, was derived from Chinese cabbage DH
      line 'FT' using a combination of isolated microspore culture and ethyl
      methanesulfonate mutagenesis. Compared with the wild-type line 'FT,' the fsm
      plants exhibited pistil abortion, and floral organs were also relatively smaller.
      Genetic analysis indicated that the phenotype of fsm is controlled by a single
      recessive nuclear gene. Morphological observations revealed that the presence of
      abnormal ovules in fsm likely influenced normal fertilization process, ultimately
      leading to female sterility. Comparative transcriptome analysis on the flower
      buds of 'FT' and fsm using RNA-Seq revealed a total of 1,872 differentially
      expressed genes (DEGs). Of these, a number of genes involved in pistil
      development were identified, such as PRETTY FEW SEEDS 2 (PFS2), temperature
      induced lipocalin (TIL), AGAMOUS-LIKE (AGL), and HECATE (HEC). Furthermore, GO
      and KEGG pathway enrichment analyses of the DEGs suggested that a variety of
      biological processes and metabolic pathways are significantly enriched during
      pistil development. In addition, the expression patterns of 16 DEGs, including
      four pistil development-related genes and 12 floral organ development-related
      genes, were analyzed using qRT-PCR. A total of 31,272 single nucleotide
      polymorphisms were specifically detected in fsm. These results contribute to shed
      light on the regulatory mechanisms underlying pistil development in Chinese
      cabbage.

PMID- 28443129
TI  - Maximum Plant Uptakes for Water, Nutrients, and Oxygen Are Not Always Met by
      Irrigation Rate and Distribution in Water-based Cultivation Systems.
AB  - Growing on rooting media other than soils in situ -i.e., substrate-based growing-
      allows for higher yields than soil-based growing as transport rates of water,
      nutrients, and oxygen in substrate surpass those in soil. Possibly water-based
      growing allows for even higher yields as transport rates of water and nutrients
      in water surpass those in substrate, even though the transport of oxygen may be
      more complex. Transport rates can only limit growth when they are below a rate
      corresponding to maximum plant uptake. Our first objective was to compare
      Chrysanthemum growth performance for three water-based growing systems with
      different irrigation. We compared; multi-point irrigation into a pond (DeepFlow);
      one-point irrigation resulting in a thin film of running water (NutrientFlow) and
      multi-point irrigation as droplets through air (Aeroponic). Second objective was
      to compare press pots as propagation medium with nutrient solution as propagation
      medium. The comparison included DeepFlow water-rooted cuttings with either the
      stem 1 cm into the nutrient solution or with the stem 1 cm above the nutrient
      solution. Measurements included fresh weight, dry weight, length, water supply,
      nutrient supply, and oxygen levels. To account for differences in radiation sum
      received, crop performance was evaluated with Radiation Use Efficiency (RUE)
      expressed as dry weight over sum of Photosynthetically Active Radiation. The
      reference, DeepFlow with substrate-based propagation, showed the highest RUE,
      even while the oxygen supply provided by irrigation was potentially growth
      limiting. DeepFlow with water-based propagation showed 15-17% lower RUEs than the
      reference. NutrientFlow showed 8% lower RUE than the reference, in combination
      with potentially limiting irrigation supply of nutrients and oxygen. Aeroponic
      showed RUE levels similar to the reference and Aeroponic had non-limiting
      irrigation supply of water, nutrients, and oxygen. Water-based propagation
      affected the subsequent cultivation in the DeepFlow negatively compared to
      substrate-based propagation. Water-based propagation resulted in frequent
      transient discolorations after transplanting in all cultivation systems,
      indicating a factor, other than irrigation supply of water, nutrients, and
      oxygen, influencing plant uptake. Plant uptake rates for water, nutrients, and
      oxygen are offered as a more fundamental way to compare and improve growing
      systems.

PMID- 28443130
TI  - Modular Design of Picroside-II Biosynthesis Deciphered through NGS Transcriptomes
      and Metabolic Intermediates Analysis in Naturally Variant Chemotypes of a
      Medicinal Herb, Picrorhiza kurroa.
AB  - Picroside-II (P-II), an iridoid glycoside, is used as an active ingredient of
      various commercial herbal formulations available for the treatment of liver
      ailments. Despite this, the knowledge of P-II biosynthesis remains scarce owing
      to its negligence in Picrorhiza kurroa shoots which sets constant barrier for
      function validation experiments. In this study, we utilized natural variation for
      P-II content in stolon tissues of different P. kurroa accessions and deciphered
      its metabolic route by integrating metabolomics of intermediates with
      differential NGS transcriptomes. Upon navigating through high vs. low P-II
      content accessions (1.3-2.6%), we have established that P-II is biosynthesized
      via degradation of ferulic acid (FA) to produce vanillic acid (VA) which acts as
      its immediate biosynthetic precursor. Moreover, the FA treatment in vitro at 150
      MUM concentration provided further confirmation with 2-fold rise in VA content.
      Interestingly, the cross-talk between different compartments of P. kurroa, i.e.,
      shoots and stolons, resolved spatial complexity of P-II biosynthesis and
      consequently speculated the burgeoning necessity to bridge gap between VA and P
      II production in P. kurroa shoots. This work thus, offers a forward looking
      strategy to produce both P-I and P-II in shoot cultures, a step toward providing
      a sustainable production platform for these medicinal compounds via-a-vis
      relieving pressure from natural habitat of P. kurroa.

PMID- 28443131
TI  - A Bioinformatics-Based Alternative mRNA Splicing Code that May Explain Some
      Disease Mutations Is Conserved in Animals.
AB  - Deep sequencing of cDNAs made from spliced mRNAs indicates that most coding genes
      in many animals and plants have pre-mRNA transcripts that are alternatively
      spliced. In pre-mRNAs, in addition to invariant exons that are present in almost
      all mature mRNA products, there are at least 6 additional types of exons, such as
      exons from alternative promoters or with alternative polyA sites, mutually
      exclusive exons, skipped exons, or exons with alternative 5' or 3' splice sites.
      Our bioinformatics-based hypothesis is that, in analogy to the genetic code,
      there is an "alternative-splicing code" in introns and flanking exon sequences,
      analogous to the genetic code, that directs alternative splicing of many of the
      36 types of introns. In humans, we identified 42 different consensus sequences
      that are each present in at least 100 human introns. 37 of the 42 top consensus
      sequences are significantly enriched or depleted in at least one of the 36 types
      of introns. We further supported our hypothesis by showing that 96 out of 96
      analyzed human disease mutations that affect RNA splicing, and change alternative
      splicing from one class to another, can be partially explained by a mutation
      altering a consensus sequence from one type of intron to that of another type of
      intron. Some of the alternative splicing consensus sequences, and presumably
      their small-RNA or protein targets, are evolutionarily conserved from 50 plant to
      animal species. We also noticed the set of introns within a gene usually share
      the same splicing codes, thus arguing that one sub-type of splicesosome might
      process all (or most) of the introns in a given gene. Our work sheds new light on
      a possible mechanism for generating the tremendous diversity in protein structure
      by alternative splicing of pre-mRNAs.

PMID- 28443132
TI  - Disease Resistance and the Definition of Genetic Enhancement.
AB  - Recent gene editing experiments carried out in human embryos have raised the
      question of whether interventions like the introduction of a CCR5-Delta32
      deletion, which could provide heritable resistance to HIV infection, ought to be
      considered enhancements. Many authors have used the term "enhancement" in
      different ways, some based on patients' biomedical outcomes and others on their
      social context. These classifications are often considered overly imprecise.
      Nevertheless, the concept of "enhancement" could affect the ways in which these
      applications are regulated in different jurisdictions, the availability of
      coverage by insurers or public health care, and the force of public opinion in
      shaping future policy on gene editing. In order to ethically situate resistance
      to communicable disease with reference to other techniques, this article provides
      an overview of its similarities and differences with disease gene therapy in
      embryos, gene therapy in consenting adults, and vaccination. In discussing key
      ethical features of CCR5-Delta32 deletion (including its frequency in various
      populations, biological mechanism, benefits for individuals, and use in previous
      clinical trials) we offer some potential guideposts for the continuing discussion
      on how to classify "enhancements" in the age of CRISPR gene editing.

PMID- 28443133
TI  - Analysis of Purified Pancreatic Islet Beta and Alpha Cell Transcriptomes Reveals
      11beta-Hydroxysteroid Dehydrogenase (Hsd11b1) as a Novel Disallowed Gene.
AB  - We and others have previously identified a group of genes, dubbed "disallowed,"
      whose expression is markedly lower in pancreatic islets than in other mammalian
      cell types. Forced mis-expression of several members of this family leads to
      defective insulin secretion, demonstrating the likely importance of disallowance
      for normal beta cell function. Up to now, transcriptomic comparisons have been
      based solely on data from whole islets. This raises the possibilities that (a)
      there may be important differences in the degree of disallowance of family
      members between beta and other either neuroendocrine cells; (b) beta (or alpha)
      cell disallowed genes may have gone undetected. To address this issue, we survey
      here recent massive parallel sequencing (RNA-Seq) datasets from purified mouse
      and human islet cells. Our analysis reveals that the most strongly disallowed
      genes are similar in beta and alpha cells, with 11beta-hydroxysteroid
      dehydrogenase (Hsd11b1) mRNA being essentially undetectable in both cell types.
      The analysis also reveals that several genes involved in cellular proliferation,
      including Yap1 and Igfbp4, and previously assumed to be disallowed in both beta
      and alpha cells, are selectively repressed only in the beta cell. The latter
      finding supports the view that beta cell growth is selectively restricted in
      adults, providing a mechanism to avoid excessive insulin production and the risk
      of hypoglycaemia. Approaches which increase the expression or activity of
      selected disallowed genes in the beta cell may provide the basis for novel
      regenerative therapies in type 2 diabetes.

PMID- 28443135
TI  - Pediatric urology: Then and now.

PMID- 28443134
TI  - Characterization of X-Chromosome Gene Expression in Bovine Blastocysts Derived by
      In vitro Fertilization and Somatic Cell Nuclear Transfer.
AB  - To better understand X-chromosome reactivation (XCR) during early development, we
      analyzed transcriptomic data obtained from bovine male and female blastocysts
      derived by in-vitro fertilization (IVF) or somatic-cell nuclear transfer (SCNT).
      We found that X-linked genes were upregulated by almost two-fold in female
      compared with male IVF blastocysts. The upregulation of X-linked genes in female
      IVFs indicated a transcriptional dimorphism between the sexes, because the mean
      autosomal gene expression levels were relatively constant, regardless of sex. X
      linked genes were expressed equivalently in the inner-cell mass and the
      trophectoderm parts of female blastocysts, indicating no imprinted inactivation
      of paternal X in the trophectoderm. All these features of X-linked gene
      expression observed in IVFs were also detected in SCNT blastocysts, although to a
      lesser extent. A heatmap of X-linked gene expression revealed that the initial
      resemblance of X-linked gene expression patterns between male and female donor
      cells turned sexually divergent in host SCNTs, ultimately resembling the patterns
      of male and female IVFs. Additionally, we found that sham SCNT blastocysts, which
      underwent the same nuclear-transfer procedures, but retained their embryonic
      genome, closely mimicked IVFs for X-linked gene expression, which indicated that
      the embryo manipulation procedure itself does not interfere with XCR in SCNT
      blastocysts. Our findings indicated that female SCNTs have less efficient XCR,
      suggesting that clonal reprogramming of X chromosomes is incomplete and occurs
      variably among blastocysts, and even among cells in a single blastocyst.

PMID- 28443136
TI  - Development of the certificate of added qualification in pediatric urology in the
      U.S.

PMID- 28443137
TI  - Pediatric urology experience in Canada: Perspectives from south of the border.

PMID- 28443138
TI  - Evolution of pediatric urology.

PMID- 28443139
TI  - Maximal testosterone suppression in the management of recurrent and metastatic
      prostate cancer.
AB  - INTRODUCTION: Testosterone suppression, or androgen-deprivation therapy (ADT), is
      an established treatment for recurrent and metastatic prostate cancer (PCa).
      Based on the accuracy and sensitivity of early assays (c. 1960-1970), the
      castrate testosterone level was set at <=1.7 nmol/l. Improved sensitivity of
      testosterone assays shows that both surgical and medical castration can achieve
      levels <0.7 nmol/l. However, the clinical implications and importance of maximum
      testosterone suppression remains a subject of controversy. This evidence-based
      review assesses prospective and retrospective clinical data, linking maximum
      suppression of testosterone with improved outcomes from ADT. METHODS: PubMed and
      conference proceedings were searched for studies assessing the impact of low
      testosterone on clinical outcomes from ADT. The key search terms included
      combinations of prostate cancer and testosterone, predictive/prognostic, and
      androgen deprivation. Results were limited to studies investigating the
      relationship between testosterone levels and clinical outcomes. RESULTS: Both
      prospective and retrospective data support a relationship between testosterone
      levels below the historical standard of 1.7 nmol/l and improved outcomes. Eight
      studies showed significant improvements in survival-related outcomes, with the
      majority of data supporting a testosterone level cutoff of <=0.7 nmol/l.
      CONCLUSIONS: Tracking both testosterone and prostate-specific antigen (PSA)
      levels has significant clinical benefits, and the serum testosterone threshold of
      <=0.7 nmol/l is a practical goal. The relative levels of testosterone and PSA may
      indicate continued hormone responsiveness or progression toward castration
      resistant prostate cancer (CRPC) and should, therefore, inform treatment
      strategy. Standardization of assay methods and clinical coordination to
      facilitate widespread access to state-of the art laboratory equipment is
      necessary to ensure accurate decision-making.

PMID- 28443141
TI  - Finding treatment success in patients unfit for radical cystectomy.

PMID- 28443140
TI  - Chemoradiotherapy in octogenarians as primary treatment for muscle-invasive
      bladder cancer.
AB  - INTRODUCTION: While radical cystectomy is the gold standard for muscle-invasive
      bladder cancer (MIBC), in octogenarians cystectomy results in a higher
      perioperative mortality rate (6.8-11.1%) than in younger patients (2.2%).
      Trimodality therapy is a bladder-sparing regimen composed of transurethral
      resection of bladder tumour (TURBT) and chemoradiotherapy, with intent for
      salvage cystectomy, and has a 62.5-90% initial complete response rate. In this
      study, we evaluate TURBT and chemoradiotherapy without salvage cystectomy in
      medically inoperable octogenarian patients. METHODS: We identified a
      retrospective cohort of patients aged 80-89 years with invasive urothelial
      carcinoma who received combination chemoradiotherapy between 2008 and June 2014.
      Outcomes were evaluated by Kaplan-Meier (KM) and Cox regression. RESULTS: In 40
      patients, the mean age was 84.5 years (interquartile range [IQR] 83-86).
      Seventeen patients received hypofractionated, low-dose radiotherapy (LD) (37.5-40
      Gy), while 23 received conventionally fractionated radiotherapy (high-dose [HD])
      (50-65 Gy). Mean overall survival (OS) was 20.7 months (IQR 12.75-23.25), while
      mean recurrence-free survival (RFS) was 13.75 months (IQR 3.75-16.5). Patients
      receiving HD radiotherapy showed improved OS and local RFS (LRFS) without
      significant differences in Grade 3-4 toxicities. Univariate Cox regression
      identified hydronephrosis as a predictor of worse OS and local recurrence and HD
      radiotherapy as a predictor of improved OS and local recurrence rates.
      Multivariate Cox regression identified hydronephrosis to be a significant
      predictor of LRFS. CONCLUSIONS: Primary chemoradiotherapy for inoperable patients
      with MIBC resulted in a three-year OS of 54.9% (comparable to cystectomy) and
      three-year RFS of 42.3%. Superior outcomes were associated with more aggressive
      chemoradiotherapy treatment. The results of the local control subanalyses in this
      study are hypothesis-generating due to the limited patient numbers in the cohort.

PMID- 28443142
TI  - Effects of androgen-deprivation therapy on hypercoagulability in prostate cancer
      patients: A prospective, longitudinal study.
AB  - INTRODUCTION: Androgen-deprivation therapy (ADT) is the mainstay of systemic
      therapy for advanced prostate cancer (PCa), but has significant adverse effects,
      including increasing concern for cardiovascular (CV) and thromboembolic (TE)
      complications. This study carefully investigates any relationship between ADT use
      and hypercoagulability as a possible mechanism of these adverse effects. METHODS:
      We performed a prospective, longitudinal study in a cohort of patients with
      advanced PCa initiating ADT (n=18). Controls included men with biochemical
      failure after local therapy on watchful waiting (n=10), as well as healthy
      controls (n=8). Global hemostasis was evaluated using the sensitive global
      hemostasis assay, thromboelastography (TEG). Patients were evaluated at baseline
      and every three months for a minimum of 12 months. RESULTS: The results of the
      TEG studies demonstrated 14/18 (78%) of advanced PCa patients had evidence of a
      hypercoagulable state before initiating therapy. Significant baseline
      hypercoagulability was documented in this cohort compared to the two control
      groups. ADT did not appear to exacerbate hypercoagulability over time as a whole:
      only 10/18 (56%) patients had TEG findings consistent with hypercoagulability at
      the end of study. However, 3/18 (17%) PCa patients initiating ADT had
      significantly new hypercoagulable TEG changes on treatment compared to baseline.
      CONCLUSIONS: This prospective pilot study demonstrates a complex interaction
      between ADT and hypercoagulable state in men with advanced PCa. TEG abnormalities
      were mostly associated with volume of cancer as compared to ADT use; however, it
      is possible that ADT may lead to hypercoagulability in a subset of men,
      suggesting that sensitive monitoring of coagulation of men on ADT could help
      identify those at risk of developing CV/TE complications. Study limitations
      include the relatively small cohort of men followed after initiating ADT and
      these results require confirmation in a larger trial to rule out subtle effects
      on hypercoagulability.

PMID- 28443143
TI  - Does androgen-deprivation therapy for prostate cancer increase the risk for
      thromboembolic disease?

PMID- 28443144
TI  - Modern-day prostate cancer is not meaningfully associated with lower urinary
      tract symptoms: Analysis of a propensity score-matched cohort.
AB  - INTRODUCTION: We sought to determine if prostate cancer (PCa) is associated with
      worse lower urinary tract symptoms (LUTS) than matched benign prostates, with
      attention to cancer characteristics, in a contemporary cohort. METHODS: Using a
      single-institution database (January 1, 2009-June 30, 2013), men diagnosed with
      PCa on biopsy and controls with negative biopsies were matched 1:1 on age,
      prostate volume, and a propensity score predicting the probability of PCa
      diagnosis. International Prostate Symptom Score (IPSS) was compared between PCa
      cases and controls using paired statistics, stratifying on grade, cancer volume,
      stage, and D'Amico risk group. Sensitivity analyses were performed separately,
      repeating the match for high-grade, high-volume, and high-stage cancers only, and
      excluding users of benign prostatic hyperplasia medications. RESULTS: In our
      cohort of 1330 men (665 with PCa), there were 284 (42.7%) Gleason 6 cancers
      (Grade Group 1), 315 (47.4%) Gleason 7 cancers (Grade Group 2-3), and 66 (9.9%)
      Gleason 8-10 cancers (Grade Group 4-5). There was no difference in IPSS between
      PCa cases (median 6.5, interquartile range [IQR] 3-12) and benign controls
      (median 7, IQR 3-13; p=0.34). Subgroup analyses based on cancer grade, volume, or
      stage, showed no significant differences in IPSS between men with and without
      PCa, except among men with cT2b-cT4 PC (median 9, IQR 5-16) vs. matched benign
      counterparts (median 8, IQR 3-12; p=0.03). Sensitivity analyses supported these
      findings. CONCLUSIONS: Modern PCa does not appear to be associated with worse
      LUTS compared to benign prostates of the same size. Outlet obstruction is likely
      a late event in the natural history of PCa. This has implications for timely PCa
      detection, which should ideally be prior to the onset of LUTS.

PMID- 28443145
TI  - Initial single-centre Canadian experience with 18F-fluoromethylcholine positron
      emission tomography-computed tomography (18F-FCH PET/CT) for biochemical
      recurrence in prostate cancer patients initially treated with curative intent.
AB  - INTRODUCTION: We sought to determine predictive factors (patient and prostate
      specific antigen [PSA] characteristics) for 18F-fluoromethylcholine positron
      emission tomography-computed tomography (18F-FCH PET/CT) positivity in the
      context of biochemical recurrence after local treatment of prostate cancer (PCa)
      with curative intent. METHODS: This is a retrospective study including 60 18F-FCH
      PET/CT scans of patients with biochemical recurrence after initial radical
      prostatectomy (RP), external beam radiation therapy (EBRT), or focal high
      intensity focused ultrasound (HIFU) with curative intent. The results were
      compared to findings on magnetic resonance imaging (MRI), computed tomography
      (CT), bone scan (BS), and histological analysis when available. Univariate
      analysis was performed to correlate results with patient characteristics.
      RESULTS: Thirty-eight (63.3%) scans were positive, 17 (28.3%) negative, and 5
      (8.3%) equivocal. Of the positive scans, 16 demonstrated local recurrence, 12
      regional/distant lymph nodes, five bone metastasis, and five local and distant
      recurrences. Among the 22 PET/CTs showing metastasis, conventional imaging was
      performed in 16 patients (72.7%). Of these, it demonstrated the lesion(s) found
      on PET/CT in eight patients (50.0%), was negative in seven (43.8%), and equivocal
      in one (6.3%). The trigger PSA (p=0.04), prostate-specific antigen velocity
      (PSAV) (p=0.03), and prostate-specific antigen doubling time (PSADT) (p=0.046)
      were significantly different when comparing positive and negative scans. Patients
      with positive scans were more likely to have received EBRT initially (odds ratio
      [OR] 11.0, 95% confidence interval [CI] 2.2-55.3). A trigger PSA of 2.6 ng/mL had
      a sensitivity of 84% and specificity of 65% for a positive scan. PET/CT changed
      the clinical management plan in 17 patients (28.3%). CONCLUSIONS: 18F-FCH PET/CT
      demonstrates a high detection rate for local and distant recurrences after
      localized PCa treatment. A trigger PSA above 2.6 ng/mL seems optimal for
      appropriate patient selection.

PMID- 28443146
TI  - Can it wait? A systematic review of immediate vs. delayed surgical repair of
      penile fractures.
AB  - INTRODUCTION: Penile fractures have classically been thought to require immediate
      surgical intervention; however, recent series have described acceptable outcomes
      with delayed repair. In this systematic review, we compared complication rates
      between immediate and delayed repair of penile fractures. METHODS: A systematic
      search of MEDLINE, Embase, CENTRAL, and Web of Science was performed with
      predefined search terms between 1974 and 2015. Titles and abstracts were screened
      prior to full-text review and quality appraisal by two independent investigators.
      Abstracted outcomes included postoperative erectile dysfunction (ED), tunical
      scar formation, and penile curvature. Only studies reporting a direct comparison
      of complications following immediate (<24 hours from injury to
      presentation/surgery) and delayed (>24 hours) repair of penile fractures were
      included. RESULTS: A total of 12 studies met inclusion criteria. All were
      retrospective, observational studies of low or moderate methodological quality.
      Of the reported 502 patients, 391 underwent immediate repair and 111 delayed
      repair. In the immediate repair group, the percent of patients with postoperative
      ED, tunical scars, and curvature were 6.6%, 5.4%, and 1.8%, respectively, while
      in the delayed group, the rates of ED, tunical scars, and curvature were 4.5%
      across the board. Rates of ED and tunical scar formation following immediate
      compared to delayed repair trended towards favouring immediate repair, but did
      not differ significantly, while rates of curvature significantly favoured
      immediate repair. However, cases of curvature were typically reported as mild and
      none affected sexual functioning. CONCLUSIONS: In this systematic review, we
      demonstrated that ED and tunical scar formation rates between immediate and
      delayed repair of penile fractures were statistically similar, while immediate
      repair had a lower rate of penile curvature. Although this suggests that a brief
      delay in repair may be acceptable in select patients, the results should be
      interpreted with caution, as the included studies were of low or moderate
      methodological quality. Most importantly, this review highlights the deficiencies
      in the current penile fracture literature, setting the stage to improve the
      quality of future studies.

PMID- 28443147
TI  - Evaluation of lower urinary tract symptoms in multiple sclerosis patients: Review
      of the literature and current guidelines.
AB  - Multiple sclerosis (MS) is a unique neurological disease with a broad spectrum of
      clinical presentations that are time- and disease course-related. MS plaque
      location (intracranial and/or spinal) is a key feature in the pathophysiology of
      disease-related lower urinary tract symptoms (LUTS). The prevalence of these
      symptoms in MS patients is very high, with nearly 90% of them experiencing some
      degree of voiding dysfunction and/or incontinence. LUTS rarely present as primary
      MS manifestations and usually appear 6-8 years after the initial diagnosis.
      Symptom severity usually correlates with the disability status of patients.
      Patient assessment comprises clinical and advanced investigations. Each patient
      should be evaluated uniquely, after taking into account his/her symptoms, disease
      course and length, comorbidities, physical status, and medications. Basic
      investigation includes detailed history-taking, physical examination, and post
      void residual volume measurement. Advanced evaluation consists of imaging and
      specific testing, with pivotal importance on urodynamic study.

PMID- 28443148
TI  - Raising awareness of the urological manifestations of multiple sclerosis.

PMID- 28443150
TI  - Your CUASF: Keeping Canada's urological research legacy alive.

PMID- 28443149
TI  - Inverted urothelial papilloma: A review of diagnostic pitfalls and clinical
      management.
AB  - Inverted urothelial papilloma (IUP) is a rare, non-invasive endophytic lesion
      that accounts for 1-2% of urothelial tumours. On cystoscopy, IUP appears as a
      pedunculated/papillary mass with a smooth surface. On microscopy, IUP has an
      endophytic growth pattern with the bulk of the tumour covered by a superficial
      layer of urothelium, which can be hyperplastic or attenuated. The cytology should
      be bland, with uniform, spindled cells arranged in anastomosing trabeculae and
      cords with peripheral palisading of basaloid cells. Exophytic papillae and
      mitotic activity should be absent or focal. Pseudoglandular spaces and squamous
      metaplasia may also be present. There are distinct molecular differences between
      IUP and urothelial carcinoma (UC). IUP rarely has mutations of FGFR3, homozygous
      loss of 9p21, or gain of chromosomes 3, 7, and 17, whereas these mutations are
      frequently seen in UC. In addition, IUP is much less likely to have TERT
      mutations compared to UC. Immunohistochemistry can also be helpful in
      distinguishing the two entities as IUP is typically negative for CK20 and has a
      low Ki-67 proliferation index. Positivity for p53 may be seen in a minority of
      IUP. IUP can recur and be seen in association with UC. Distinguishing IUP from UC
      can be difficult due to the similarity between the two entities both on
      cystoscopy and histology, as up to 25% of UCs will also have inverted growth.
      Given the morphologic variants of IUP and UC, it is possible for a diagnostic
      error to occur, which can significantly impact patient management.

PMID- 28443151
TI  - ?

PMID- 28443152
TI  - Supplementary data: Maximal testosterone suppression in the management of
      recurrent and metastatic prostate cancer.

PMID- 28443153
TI  - Supplementary data: Chemoradiotherapy in octogenarians as primary treatment for
      muscle-invasive bladder cancer.

PMID- 28443155
TI  - Egg consumption and risk of non-alcoholic fatty liver disease.
AB  - AIM: To evaluate the association between egg consumption and risk of non
      alcoholic fatty liver disease (NAFLD) development. METHODS: This case-control
      study was conducted on individuals who were referred to two hepatology clinics in
      Tehran, Iran in 2015. The study included 169 patients with NAFLD and 782
      controls. Egg consumption was estimated using a validated food frequency
      questionnaire. The participants were categorized according to the frequency of
      their egg consumption during the previous year: Less than two eggs per week, two
      to three eggs per week, and four or more eggs per week. RESULTS: In the crude
      model, participants who consumed 2 to 3 eggs per week, were 3.56 times more
      likely to have NAFLD in comparison to those who consumed less than 2 eggs per
      week (OR: 3.56; 95%CI: 2.35-5.31). Adjustment for known risk factors of NAFLD
      strengthened this significant association so that individuals have consumed two
      to three eggs per week had 3.71 times higher risk of NAFLD than those who have
      eaten less than two eggs per week (OR: 3.71; 95%CI: 1.91, 7.75). CONCLUSION: Our
      data indicate that higher egg consumption in common amount of usage is associated
      with higher risk of NAFLD.

PMID- 28443158
TI  - Building a Research.

PMID- 28443154
TI  - Drug-induced liver injury: Do we know everything?
AB  - Interest in drug-induced liver injury (DILI) has dramatically increased over the
      past decade, and it has become a hot topic for clinicians, academics,
      pharmaceutical companies and regulatory bodies. By investigating the current
      state of the art, the latest scientific findings, controversies, and guidelines,
      this review will attempt to answer the question: Do we know everything? Since the
      first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have
      been identified to date, however, much of our knowledge of diagnostic and
      pathophysiologic principles remains unchanged. Clinically ranging from
      asymptomatic transaminitis and acute or chronic hepatitis, to acute liver
      failure, DILI remains a leading causes of emergent liver transplant. The
      consumption of unregulated herbal and dietary supplements has introduced new
      challenges in epidemiological assessment and clinician management. As such,
      numerous registries have been created, including the United States Drug-Induced
      Liver Injury Network, to further our understanding of all aspects of DILI. The
      launch of LiverTox and other online hepatotoxicity resources has increased our
      awareness of DILI. In 2013, the first guidelines for the diagnosis and management
      of DILI, were offered by the Practice Parameters Committee of the American
      College of Gastroenterology, and along with the identification of risk factors
      and predictors of injury, novel mechanisms of injury, refined causality
      assessment tools, and targeted treatment options have come to define the current
      state of the art, however, gaps in our knowledge still undoubtedly remain.

PMID- 28443157
TI  - Hepatic encephalopathy before and neurological complications after liver
      transplantation have no impact on the employment status 1 year after
      transplantation.
AB  - AIM: To investigate the impact of hepatic encephalopathy before orthotopic liver
      transplantation (OLT) and neurological complications after OLT on employment
      after OLT. METHODS: One hundred and fourteen patients with chronic liver disease
      aged 18-60 years underwent neurological examination to identify neurological
      complications, neuropsychological tests comprising the PSE-Syndrome-Test yielding
      the psychometric hepatic encephalopathy score, the critical flicker frequency and
      the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS),
      completed a questionnaire concerning their occupation and filled in the short
      form 36 (SF-36) to assess health-related quality of life before OLT and 12 mo
      after OLT, if possible. Sixty-eight (59.6%) patients were recruited before OLT,
      while on the waiting list for OLT at Hannover Medical School [age: 48.7 +/- 10.2
      years, 45 (66.2%) male], and 46 (40.4%) patients were included directly after
      OLT. RESULTS: Before OLT 43.0% of the patients were employed. The patients not
      employed before OLT were more often non-academics (employed: Academic/non
      academic 16 (34.0%)/31 vs not employed 10 (17.6%)/52, P = 0.04), had more
      frequently a history of hepatic encephalopathy (HE) (yes/no; employed 15
      (30.6%)/34 vs not employed 32 (49.2%)/33, P = 0.05) and achieved worse results in
      psychometric tests (RBANS sum score mean +/- SD employed 472.1 +/- 44.5 vs not
      employed 443.1 +/- 56.7, P = 0.04) than those employed. Ten patients (18.2%), who
      were not employed before OLT, resumed work afterwards. The patients employed
      after OLT were younger [age median (range, min-max) employed 47 (42, 18-60) vs
      not employed 50 (31, 29-60), P = 0.01], achieved better results in the
      psychometric tests (RBANS sum score mean +/- SD employed 490.7 +/- 48.2 vs not
      employed 461.0 +/- 54.5, P = 0.02) and had a higher health-related quality of
      life (SF 36 sum score mean +/- SD employed 627.0 +/- 138.1 vs not employed 433.7
      +/- 160.8; P < 0.001) compared to patients not employed after OLT. Employment
      before OLT (P < 0.001), age (P < 0.01) and SF-36 sum score 12 mo after OLT (P <
      0.01) but not HE before OLT or neurological complications after OLT were
      independent predictors of the employment status after OLT. CONCLUSION: HE before
      and neurological complications after OLT have no impact on the employment status
      12 mo after OLT. Instead younger age and employment before OLT predict employment
      one year after OLT.

PMID- 28443156
TI  - Serum 25-hydroxyvitamin D deficiency and hepatic encephalopathy in chronic liver
      disease.
AB  - AIM: To investigate the relationship between 25-hydroxyvitamin D (25-OHD)
      deficiency and hepatic encephalopathy (HE) in patients with chronic liver disease
      (CLD). METHODS: A retrospective analysis of the results of 392 adult patients
      with chronic liver disease who were assessed for liver transplantation between
      2006 and 2010 was undertaken. HE, severity of CLD, nutritional status and 25-OHD
      were analysed in patients assessed for liver transplantation between 2006 and
      2010. Patients who presented with acute, fulminant or subacute disease, with a
      primary diagnosis of liver cancer, were assessed for re-transplantation or who
      did not have a 25-OHD measurement were excluded from the analysis. RESULTS: One
      hundred and sixty-five patients were included in this analysis. The mean age of
      all patients was 53 +/- 8 years. Moderate to severe 25-OHD deficiency was
      identified in 49 patients of whom 36 had grade 2-3 HE compared with 13 patients
      who were not encephalopathic (P <= 0.0001). Mild 25-OHD deficiency was not
      associated with HE. There was a significant correlation between the severity of
      25-OHD deficiency and the severity of liver disease (r = 0.39, P <= 0.0001) and
      disease severity and the presence of HE (P <= 0.0001). Importantly, individuals
      with 25-OHD deficiency were more likely to have a diagnosis of overt HE (OHE) at
      a significantly lower model for end stage liver disease (MELD) score than
      individuals without OHE (P <= 0.0001). This significant difference was observed
      with MELD scores from 10 to 38. CONCLUSION: 25-OHD deficiency was observed in the
      majority of patients with CLD and for the first time was found to be
      significantly worse in patients with OHE.

PMID- 28443159
TI  - Genetic Markers for Adolescent Idiopathic Scoliosis on Chromosome 19p13.3 among
      Saudi Arabian Girls.
AB  - STUDY DESIGN: Prospective case-controlled study. PURPOSE: This study aimed to
      assess genetic influence in Saudi Arabian children with adolescent idiopathic
      scoliosis (AIS). OVERVIEW OF LITERATURE: The genetic locus linked to chromosome
      19p for idiopathic scoliosis has been described. A pilot study conducted at King
      Fahd Hospital of the University, Al-Khobar showed that three microsatellite
      markers (D19S216, D19S894, and DS1034) of chromosome 19p13.3 were significant in
      Saudi Arabian females compared with healthy subjects. METHODS: A total of 100
      unrelated Saudi Arabian girls treated for AIS, their parents, healthy siblings,
      and healthy subjects were recruited for genetic analysis of markers on chromosome
      19p13.3. After informed consent was obtained from their parents, blood samples
      were collected and parametric and nonparametric linkage analyses were performed
      using GENEHUNTER ver. 2.1. Multipoint linkage analysis was used to specify an
      autosomal dominant trait with a gene frequency of 0.01 and an estimated
      penetrance of 80% at the genotypic and allelic levels. RESULTS: Five hundred
      blood samples were collected and analyzed for microsatellite markers (D19S216,
      D19S894, and DS1034) of chromosome 19p13.3. Comparison among patients, family
      members, and healthy subjects revealed no significant association between markers
      and scoliosis at the genotypic level: D19S216 (p=0.21), D19S894 (p=0.37), and
      DS1034 (p=0.25). However, at the allelic level, a statistically significant
      association was observed for marker DS1034 (p=0.008), and marker D19S216 showed
      significance between fathers and patients (p<0.001) compared with patients and
      mothers. The other two markers, D19S216 (p=0.25) and D19S894 (p=0.17), showed no
      significant association between patients and mothers. CONCLUSIONS: At the allelic
      level, marker DS1034 was significantly associated with AIS patients and their
      fathers. This allelic marker on chromosome 19p13.3 appears to be important in AIS
      etiology.

PMID- 28443160
TI  - Correlation between Preoperative Magnetic Resonance Imaging Signal Intensity
      Changes and Clinical Outcomes in Patients Surgically Treated for Cervical
      Myeloradiculopathy.
AB  - STUDY DESIGN: This was a single surgeon, single center-based retrospective study
      with prospective data collection. PURPOSE: To assess the correlation between T2
      weighted magnetic resonance imaging (MRI) signal intensity (SI) changes and
      factors such as age, duration of symptoms, baseline modified Japanese Orthopedic
      Association (mJOA) score and to determine its prognostic value in predicting
      recovery after surgery. OVERVIEW OF LITERATURE: Whether intramedullary cord T2
      weighted MRI SI changes can predict operative outcomes of cervical
      myeloradiculopathy remains debatable, with only a few prospective studies
      analyzing the same. METHODS: Forty-six consecutive patients who underwent
      cervical myeloradiculopathy were included and were followed up for an average of
      1 year. Preoperative T2-weighted MRI SI grading was performed for all patients.
      The correlation between MRI SI changes and age, duration of symptoms,
      preoperative mJOA score, and mJOA score at 1-year follow-up were analyzed.
      RESULTS: Fifteen patients had single-level (21.73%) or double-level (10.86%)
      prolapsed discs; 54.34% had degenerative cervical spondylosis with canal stenosis
      or multilevel disc prolapse and 13.07% had ossified posterior longitudinal
      ligaments. The mean age was 56.17+/-9.53 years (range, 35-81 years). The mean
      baseline mJOA score was 10.83+/-2.58 (range, 6-16), which postoperatively
      improved to 13.59+/-2.28 (range, 8-17; p<0.001). There was a statistically
      significant correlation between mJOA score at 1 year and MRI T2 SI grading
      (p=0.017). CONCLUSIONS: Patients with longer symptom durations had high grades of
      intramedullary cord T2-weighted MRI SI changes. Age and preoperative neurological
      status were not significantly correlated with the existence of intramedullary
      cord SI changes. However, patients without or with mild and diffuse
      intramedullary cord T2-weighted MRI SI changes had better postoperative
      neurological recovery than those with sharp and focal SI changes.

PMID- 28443161
TI  - Surgical Morphometry of C1 and C2 Vertebrae: A Three-Dimensional Computed
      Tomography Analysis of 180 Chinese, Indian, and Malay Patients.
AB  - STUDY DESIGN: Clinical imaging study. PURPOSE: To study the surgical morphometry
      of C1 and C2 vertebrae in Chinese, Indian, and Malay patients. OVERVIEW OF
      LITERATURE: C1 lateral mass and C2 pedicle screw fixation is gaining popularity.
      However, there is a lack of C1-C2 morphometric data for the Asian population.
      METHODS: Computed tomography analysis of 180 subjects (60 subjects each belonging
      to Chinese, Indian, and Malay populations) using simulation software was
      performed. Length and angulations of C1 lateral mass (C1LM) and C2 pedicle (C2P)
      screws were assessed. RESULTS: The predicted C1LM screw length was between 23.2
      and 30.2 mm. The safe zone of trajectories was within 11.0 degrees +/-7.7 degrees
      laterally to 29.1 degrees +/-6.2 degrees  medially in the axial plane and 37.0
      degrees +/-10.2 degrees  caudally to 20.9 degrees +/-7.8 degrees  cephalically in
      the sagittal plane. The shortest and longest predicted C2P screw lengths were
      22.1+/-2.8 mm and 28.5+/-3.2 mm, respectively. The safe trajectories were from
      25.1 degrees  to 39.3 degrees  medially in the axial plane and 32.3 degrees  to
      45.9 degrees  cephalically in the sagittal plane. CONCLUSIONS: C1LM screw length
      was 23-30 mm with the axial safe zone from 11 degrees  laterally to 29 degrees 
      medially and sagittal safe zone at 21 degrees  cephalically. C2P screw length was
      22-28 mm with axial safe zone from 26 degrees  to 40 degrees  medially and
      sagittal safe zone from 32 degrees  to 46 degrees  cephalically. These data serve
      as an important reference for Chinese, Indian, and Malay populations during C1-C2
      instrumentation.

PMID- 28443162
TI  - Novel Measurement Technique for the Sagittal Vertical Axis and Its Clinical
      Application in Adult Spinal Deformity.
AB  - STUDY DESIGN: Prospective physical measurement of the sagittal vertical axis
      (SVA). PURPOSE: To evaluate a simple method for measuring SVA by analyzing its
      relationship with radiographic measurements and clinical appearance. OVERVIEW OF
      LITERATURE: No studies have examined physical measurements using the cranial
      center of gravity (CCG) in a relaxed standing position. METHODS: The physical
      measurement of the horizontal distance between CCG and spina iliaca posterior
      superior (CCG-SIPS) was measured using a straight ruler in 252 healthy volunteers
      and 56 patients with adult spinal deformity. Health-related quality of life
      (HRQOL) was evaluated using the Oswestry disability index (ODI), and clinical
      symptoms were assessed according to standing status and the presence of
      gastroesophageal reflux disease (GERD). RESULTS: CCG-SIPS increased with age in
      the volunteer group and strongly correlated with radiographic SVA in the patient
      group (r=0.984). Differences increased between CCG-SIPS in patients in the
      relaxed position and radiographic SVA with an increase in sagittal malalignment
      (r=0.692, p<0.001). ODI with high sagittal malalignment (CCG-SIPS>120 mm) was
      significantly larger in the patient group than in the group with low sagittal
      malalignment (59.9+/-18.8 vs. 45.1+/-17.0; p=0.004); these patients (CCG-SIPS>120
      mm) needed crutches or walkers for standing. The patient group with GERD had
      significantly larger sagittal malalignment than the group without GERD (160.3 mm
      vs. 81.0 mm). CONCLUSIONS: The CCG-SIPS correlated with age and strongly
      reflected radiographic SVA and HRQOL in the patients. Moreover, it reflects a
      relaxed posture without a backward shift in the radiographic position even in
      patients with severe sagittal malalignment. The critical limit of CCG-SIPS can be
      relevant to clinical appearance, including standing assistance (>120 mm) and the
      existence of GERD (>150 mm). Thus, it will be a useful predictor of true SVA in
      clinical practice before radiographic evaluation.

PMID- 28443163
TI  - Using Magnetic Resonance Myelography to Improve Interobserver Agreement in the
      Evaluation of Lumbar Spinal Canal Stenosis and Root Compression.
AB  - STUDY DESIGN: Cross-sectional retrospective study designed to assess
      interobserver agreement. PURPOSE: To investigate if interobserver agreement using
      magnetic resonance imaging (MRI) in the evaluation of lumbar spinal canal
      stenosis and root compression can be improved upon combination with magnetic
      resonance myelography (MRM). OVERVIEW OF LITERATURE: The interpretation of lumbar
      spinal MRI, which is the imaging modality of choice, often has a significant
      influence on the diagnosis and treatment of low back pain. However, using MRI
      alone, substantial interobserver variability has been reported in the evaluation
      of lumbar spinal canal stenosis and nerve root compression. METHODS: Hardcopies
      of 30 lumbar spinal MRI (containing a total of 150 disk levels) as well as MRM
      films were separately reviewed by two radiologists and a neurosurgeon. At each
      intervertebral disk, the observers were asked to evaluate the thecal sac for the
      presence and degree of spinal stenoses (mild, moderate, or severe) and presence
      of root canal compression. Interobserver agreement was measured using weighted
      kappa statistics. RESULTS: Regarding lumbar spinal canal stenosis, interobserver
      agreement between the two radiologists was moderate (kappa, 0.4) for MRI and good
      (kappa, 0.6) for combination with MRM. However, the agreement between the
      radiologist and neurosurgeon remained fair for MRI alone or in combination with
      MRM (kappa, 0.38 and 033, respectively). In the evaluation of nerve root
      compression, interobserver agreement between the radiologists improved from
      moderate (kappa, 0.57) for MRI to good (kappa, 0.73) after combination with MRM;
      moderate agreement between the radiologist and neurosurgeon was noted for both
      MRI alone and after combination with MRM (kappa, 0.58 and 0.56, respectively).
      CONCLUSIONS: Interobserver agreement in the evaluation of lumbar spinal canal
      stenosis and root compression between the radiologists improved when MRM was
      combined with MRI, relative to MRI alone.

PMID- 28443164
TI  - Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion Provides
      Sustained Improvements in Clinical and Radiological Outcomes up to 5 Years
      Postoperatively in Patients with Neurogenic Symptoms Secondary to
      Spondylolisthesis.
AB  - STUDY DESIGN: Retrospective review of prospective registry data. PURPOSE: To
      determine 5-year clinical and radiological outcomes of single-level instrumented
      minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in patients
      with neurogenic symptoms secondary to spondylolisthesis. OVERVIEW OF LITERATURE:
      MIS-TLIF and open approaches have been shown to yield comparable outcomes. This
      is the first study to assess MIS-TLIF outcomes using the minimal clinically
      important difference (MCID) criterion. METHODS: The outcomes of 56 patients
      treated by a single surgeon, including the Oswestry disability index (ODI),
      neurogenic symptom score, short-form 36 questionnaire (SF-36), and visual analog
      scale (VAS) scores for back pain (BP), and leg pain (LP), were collected
      prospectively for up to 5 years postoperatively. Radiological outcomes included
      adjacent segment degeneration, fusion, cage subsidence, and screw loosening
      rates. RESULTS: Our patients were predominantly female (71.4%) and had a mean age
      of 53.7+/-11.3 years and mean body mass index of 25.7+/-3.7 kg/m2. The mean
      operative time, blood loss, time to ambulation, and hospitalization were 167+/-49
      minutes, 126+/-107 mL, 1.2+/-0.4 days, and 2.8+/-1.1 days, respectively. The mean
      fluoroscopic time was 58.4+/-33 seconds, and the mean postoperative intravenous
      morphine dose was 8+/-2 mg. Regarding outcomes, postoperative scores improved
      relative to preoperative scores, and this was sustained across various time
      points for up to 5 years (p<0.001). Improvements in ODI, SF-36, VAS-BP, and VAS
      LP all met the MCID criterion. Notably, 5.4% of our patients developed clinically
      significant adjacent segment disease during follow-up, and 7 minor complications
      were reported. CONCLUSIONS: Single-level instrumented MIS-TLIF is suitable for
      patients with neurogenic symptoms secondary to lumbar spondylolisthesis and is
      associated with an acceptable complication rate. Both clinical and radiological
      outcomes were sustained up to 5 years postoperatively, with many patients
      achieving an MCID.

PMID- 28443165
TI  - Long-Term Outcomes of In Situ Fusion for Treating Dysplastic Spondylolisthesis.
AB  - STUDY DESIGN: Retrospective, observational, single-center study. PURPOSE: To
      investigate the long-term outcomes of in situ fusion procedures for treating
      dysplastic spondylolisthesis. OVERVIEW OF LITERATURE: In situ fusion performed in
      patients with dysplastic spondylolisthesis avoids the development of nerve
      complications. METHODS: In total, 12 of 28 patients who underwent in situ fusion
      for treating dysplastic spondylolisthesis at Chiba University Hospital from 1974
      to 2004 were followed up in August 2013. Surgical complications were evaluated.
      Low back pain and leg pain were assessed using a visual analog scale (VAS).
      Vertebral alignment, including the lumbosacral angle and lumbar lordosis angle
      measurement on radiographic images (profile view in the neutral standing
      position), was evaluated during preoperative, postoperative, and final
      examinations. RESULTS: The mean follow-up duration, patient age at the final
      examination, and patient age at operation were 20.0+/-7.2, 42.3+/-13.3, and
      22.3+/-11.4 years, respectively. No complications were reported. Mean VAS scores
      for low back pain and leg pain were significantly lower at the final examination
      than at the preoperative examination (p<0.05). At the preoperative,
      postoperative, and final examinations, the mean lumbosacral angle was 32.3
      degrees +/-14.2 degrees , 33.7 degrees +/-11.8 degrees , and 36.5 degrees +/-16.4
      degrees , while the mean lumbar lordosis angle was 51.0 degrees +/-14.8 degrees ,
      48.6 degrees +/-18.8 degrees , and 49.6 degrees +/-15.5 degrees , respectively.
      No significant differences were noted among these values across the different
      time periods (p<0.05). CONCLUSIONS: In situ fusion performed in patients with
      dysplastic spondylolisthesis avoids the development of nerve complications such
      as nerve paralysis that may occur after repositioning operation and maintains
      appropriate long-term sagittal alignment, even 20 years after operation.

PMID- 28443166
TI  - Correlation between Topographic Parameters Obtained by Back Surface Topography
      Based on Structured Light and Radiographic Variables in the Assessment of Back
      Morphology in Young Patients with Idiopathic Scoliosis.
AB  - STUDY DESIGN: Optical cross-sectional study. PURPOSE: To study the correlation
      between asymmetry of the back (measured by means of surface topography) and
      deformity of the spine (quantified by the Cobb angle). OVERVIEW OF LITERATURE:
      The Cobb angle is considered the gold standard in diagnosis and follow-up of
      scoliosis but does not correctly characterize the three-dimensional deformity of
      scoliosis. Furthermore, the exposure to ionizing radiation may cause harmful
      effects particularly during the growth stage, including breast cancer and other
      tumors. METHODS: Patients aged 13.15+/-1.96 years (range, 7-17 years; n=88) with
      Cobb angle greater than 10 degrees  were evaluated with X-rays and our back
      surface topography method through three variables: axial plane (DHOPI), coronal
      plane (POTSI), and profile plane (PC). Pearson's correlation was applied to
      determine the correlation between topographic and radiographic variables. One-way
      analysis of variance and Bonferroni correction were used to compare groups with
      different grades of scoliosis. Significance was set at p<0.01 and, in some cases,
      at p<0.05. RESULTS: We detected a positive, statistically significant correlation
      between Cobb angle with DHOPI (r=0.810) and POTSI (r=0.629) and between PC
      variables with thoracic kyphosis angle (r=0.453) and lordosis lumbar angle
      (r=0.275). In addition, we found statistically significant differences for DHOPI
      and POTSI variables according to the grade of scoliosis. CONCLUSIONS: Although
      the back surface topography method cannot substitute for radiographs in the
      diagnosis of scoliosis, correlations between radiographic and topographic
      parameters suggest that it offers additional quantitative data that may
      complement radiologic study.

PMID- 28443167
TI  - Elderly Patients Achieving Clinical and Radiological Outcomes Comparable with
      Those of Younger Patients Following Minimally Invasive Transforaminal Lumbar
      Interbody Fusion.
AB  - STUDY DESIGN: Retrospective analysis of prospective database. PURPOSE: To compare
      2-year clinical and radiological outcomes after minimally invasive transforaminal
      lumbar interbody fusion (MIS-TLIF) among "middle-age" (50-64.99 years), "young
      old" (65-74.99 years), and "old-old" (>75 years) patients. OVERVIEW OF
      LITERATURE: Owing to higher perioperative morbidity and mortality rates, elderly
      patients with degenerative lumbar conditions are occasionally denied surgical
      care, even after conservative treatment failure. MIS-TLIF advantages include
      reduced blood loss, reduced analgesia requirements, early mobilization, and
      shorter hospital stays. METHODS: Between 2007 and 2012, 22 patients (age >75
      years) treated with 1-2 level MIS-TLIF were matched with "young-old" and "middle
      age" patients (22 each) based on race, body mass index (BMI), diagnosis, spinal
      level, number of spinal levels operated upon, and bone graft type. Clinical
      outcomes included the Oswestry disability index (ODI), neurogenic symptom score
      (NSS), 36-item short form health survey (SF-36), and visual analogue scale (VAS)
      for back and leg pain. Radiological assessment included plain radiographs and
      preoperative magnetic resonance imaging (MRI) and plain radiographs at 1, 3, 6,
      and 24 months postoperatively. Fusion grade, loosening, cage migration, and
      adjacent segment degeneration were assessed. RESULTS: The groups had similar
      fluoroscopy time, operation duration, and postoperative analgesia type used. "Old
      old" patients took longer to ambulate (1.6 days) and had longer hospital stays (6
      days). All patients showed significant improvement in clinical outcome scores at
      all time-points compared with the preoperative status. "Middle-age" patients
      showed better ODI and SF-36 physical function scores than "old-old" patients
      preoperatively and 2 years post surgery. NSS, VAS (back and leg), and SF-36
      mental function scores were similar between groups preoperatively and at every
      time-point postoperatively. Minimal clinical important differences (63.6%-95.5%
      at 2 years) were achieved. Grade 1 fusion occurred in a minimum of 80% patients
      in each group 2 years post surgery. Complication rates were similar. Adjacent
      segment disease occurred in 2 patients from the "young-old" group, with no
      significant differences between groups. CONCLUSIONS: MIS-TLIF showed comparable
      results in selected "old-old" patients compared with "young-old" and "middle-age"
      patients without increased complication risks.

PMID- 28443168
TI  - An Iranian Version of the Fukushima Lumbar Spinal Stenosis Scale (FLS-25): A
      Validation Study.
AB  - STUDY DESIGN: Cross-sectional study. PURPOSE: To translate and validate the
      Fukushima lumbar spinal stenosis (LSS) scale 25 (FLS-25) for use in Iran.
      OVERVIEW OF LITERATURE: Tools measuring patient-reported outcomes should satisfy
      certain psychometric properties. METHODS: FLS-25 is a self-administered scale for
      evaluating symptoms of LSS. A forward-backward procedure was applied to translate
      the questionnaire from English into Persian. A sample of patients with LSS
      completed the questionnaire at two points in time: once before surgery and once 6
      months after the surgery. The Neurogenic Claudication Outcome Score (NCOS) was
      also used for assessment. The psychometric properties of FLS-25 were evaluated
      for internal consistency, test-retest and interobserver reliabilities,
      responsiveness to change, known-group comparison, and convergent validity.
      RESULTS: In all, 131 patients were included in the study. The mean age of the
      patients was 61.4 (standard deviation, 11.1) years. The Cronbach's alpha
      coefficient for FLS-25 was 0.89. Test-retest reliability as carried out by the
      intraclass correlation coefficient was 0.94 (95% confidence interval, 0.95).
      Interobserver agreement as measured by the kappa statistics also was found to be
      acceptable (kappa value, 0.88), and validity was found to be satisfactory. The
      instrument was able to discriminate between the subgroups of patients who
      differed in symptom severity. The correlation between FLS-25 and NCOS scores was
      excellent, indicating good convergent validity (r=0.82, p<0.001). The results
      also indicated that the instrument was responsive to change (p<0.001).
      CONCLUSIONS: The Iranian version of FLS-25 performed well, and the findings
      suggest that it is a valid measure of symptom severity in LSS patients.

PMID- 28443169
TI  - Radiographic Analysis of the Lumbosacral Juncture: Is There a Critical Sacral
      Angle for Total Disc Replacement?
AB  - STUDY DESIGN: Retrospective review of a patient cohort through a prospective
      study. PURPOSE: To determine whether there are correlations between radiographic
      measurements, including sacral slope (SS) and pelvic incidence (PI), and self
      reported clinical outcomes among single-level L5/S1 ProDisc-L patients. OVERVIEW
      OF LITERATURE: The lumbosacral juncture presents unique biomechanical challenges
      with respect to artificial disc replacement (ADR) because of its orientation and
      consequential shear loading. Reports of inferior outcomes at L5/S1 compared to
      those of the outcomes at the levels above, including increased facet joint pain,
      suggest a relationship with the sacral inclination at L5/S1. METHODS: Plain
      standing lateral radiographs of 71 patients (age, 26-65 years) who underwent ADR
      at L5/S1 for degenerative disc disease were reviewed. SS and PI were measured
      based on pretreatment and initial follow-up standing films. Patient's average
      adjusted self assessments included the Oswestry disability index and visual
      analog scale for pain 2 years after ADR. Correlation coefficients were computed
      to evaluate relationships between radiographic parameters and clinical outcomes.
      Analysis of covariance was used to evaluate multivariate relationships among
      factors, including radiographic parameters, body mass index (BMI), and clinical
      outcomes. RESULTS: SS and PI values were obtained from 71 patients. The average
      SS was 33.3 degrees  and average PI was 39.9 degrees . At the 24-month follow-up,
      no significant correlations (p>=0.05) were observed between radiographic
      parameters and clinical outcomes. BMI, age, and sex did not explain any
      variability in the relationships between clinical outcomes and SS and PI.
      CONCLUSIONS: We reviewed a large range of SS angles and found no associations
      between SS, PI, or BMI and clinical outcomes after ADR at L5/S1. These
      preliminary results demonstrate that ADR provided maintainence of pain relief and
      functional improvement for a wide range of SS angles, suggesting that steeper
      angles are not a contraindication for ADR.

PMID- 28443170
TI  - Relationships among Disability, Quality of Life, and Physical Fitness in Lumbar
      Spinal Stenosis: An Investigation of Elderly Korean Women.
AB  - STUDY DESIGN: A cross-sectional, case-control study. PURPOSE: To investigate
      associations between physical fitness measures and disabilities related to back
      pain and quality of life (QOL) by the presence of symptomatic lumbar spinal
      stenosis (LSS) in elderly Korean women. OVERVIEW OF LITERATURE: LSS leads to
      decreased functioning and reduced QOL. However, correlations among physical
      fitness, disability, and QOL have not been investigated in elderly women with
      LSS. METHODS: Participants included women aged 65 years and older (n=192),
      divided into a study group (n=38) and a control group (n=154) based on the
      presence/absence of LSS. All participants underwent physical function and fitness
      tests. Oswestry disability index (ODI) scores and EuroQol five-dimensional
      questionnaire (EQ-5D-5L) scores were used to assess disability and health-related
      QOL. RESULTS: The results for the handgrip strength, sit-and-reach, functional
      reach, and timed up and go (TUG) tests were significantly higher in the control
      group than the LSS group. ODI scores were significantly higher and EQ-5D-5L
      scores significantly lower in the LSS group. TUG and functional reach test scores
      were significantly correlated with ODI scores, and handgrip strength was strongly
      interrelated with ODI and EQ-5D-5L scores in the LSS group. No other physical
      fitness measures showed statistically significant relationships with ODI or EQ-5D
      5L scores. CONCLUSIONS: In elderly Korean women with LSS, back pain-related
      disability and QOL are significantly associated with some physical fitness
      parameters such as handgrip strength. Handgrip strength reflects general muscle
      strength, which is significantly interrelated with the level of disability and
      QOL. Our results suggest that enhancing generalized muscle strength helps to
      reduce disability due to back pain and improve QOL in patients with LSS.

PMID- 28443171
TI  - A Prospective Study of Clinical and Radiological Outcomes of Zero-Profile Cage
      Screw Implants for Single-Level Anterior Cervical Discectomy and Fusion: Is
      Segmental Lordosis Maintained at 2 Years?
AB  - STUDY DESIGN: Prospective cohort study. PURPOSE: To study clinicoradiological
      parameters of zero-profile cage screw used for anterior cervical discectomy and
      fusion (ACDF). OVERVIEW OF LITERATURE: Radiological parameters of various
      implants used for ACDF are available, but those for zero-profile cage are sparse.
      METHODS: Patients with unilateral intractable brachialgia due to single-level
      cervical disc prolapse between April 1, 2011 and March 31, 2014 were included.
      Clinical assessment included arm and neck pain using visual analogue score (VAS)
      and neck disability index (NDI) scores. Radiological assessment included motion
      segment height, adjacent disc height (upper and lower), segmental and cervical
      lordosis, implant subsidence, and pseudoarthrosis. Follow-ups were scheduled at
      1, 3, 6, 12, and 24 months. RESULTS: Thirty-four patients (26 males, 8 females)
      aged 30-50 years (mean, 42.2) showed excellent clinical improvement based on VAS
      scores (7.4-0 for arm and 2.0-0.6 for neck pains). Postoperative disc height
      improved by 11.33% (p<0.001), but at 2 years, the score deteriorated by 7.03%
      (p<0.001). Difference in the adjacent segment disc height at 2 years was 0.08%
      (p=0.8) in upper and 0.16% (p<0.001) in lower disc spaces. Average segmental
      lordosis achieved was 5.59 degrees  (p<0.001) from a preoperative kyphosis of
      0.88 degrees ; at 2 years, an average loss of 7.05 degrees  (p<0.001) occurred,
      resulting in an average segmental kyphosis of 1.38 degrees . Cervical lordosis
      improved from 11.59 degrees  to 14.88 degrees  (p=0.164), and at 2 years, it
      progressively improved to 22.59 degrees  (p<0.001). Three patients showed bone
      formation and two mild protrusion of the implant at 2 years without
      pseudoarthrosis/implant failure. CONCLUSIONS: The zero-profile cage screw device
      provides good fusion and cervical lordosis but is incapable of maintaining the
      segmental lordosis achieved up to a 2-year follow-up. We also recommend caution
      when using it in patients with small vertebrae.

PMID- 28443172
TI  - Does Discontinuing Teriparatide Treatment and Replacing It with Bisphosphonate
      Maintain the Volume of the Bone Fusion Mass after Lumbar Posterolateral Fusion in
      Women with Postmenopausal Osteoporosis?
AB  - STUDY DESIGN: Retrospective case series. PURPOSE: The purpose of this study was
      to determine whether discontinuing teriparatide treatment and replacing it with
      bisphosphonate treatment maintains the volume of the fusion mass after
      posterolateral fusion (PLF) in women with postmenopausal osteoporosis. OVERVIEW
      OF LITERATURE: Clinical data support the efficacy of parathyroid hormone (PTH)
      for lumbar PLF. However, the use of PTH is limited to 2 years. METHODS: We
      treated 19 women diagnosed with osteoporosis and degenerative spondylolisthesis
      with teriparatide (20 ug daily subcutaneously). All patients underwent one-level
      instrumented PLF. Teriparatide was used during 2 months prior to surgery and more
      than 8 months after surgery. After discontinuing teriparatide treatment, all
      patients used bisphosphonate (17.5 mg risedronate weekly, oral administration).
      Area of the fusion mass across the transverse processes at one segment was
      determined on an anteroposterior radiograph at 1, 2, and 3 years after surgery.
      RESULTS: We followed 19 patients for 3 years. The average duration of
      teriparatide treatment was 11.5 months. The bone union rate was 95%. The average
      area of the bone fusion mass was not significantly different between the right
      and left sides at 1, 2, or 3 years after surgery (p>0.05). CONCLUSIONS: This
      study showed that replacing teriparatide treatment with bisphosphonate maintained
      the bone fusion mass volume after PLF in women with postmenopausal osteoporosis.

PMID- 28443173
TI  - Qualitative Grading as a Tool in the Management of Multilevel Lumbar Spine
      Stenosis.
AB  - STUDY DESIGN: This is a prospective study that was undertaken at a single centre
      and involved 80 consecutive patients diagnosed with lumbar spinal stenosis (LSS).
      PURPOSE: The aim of the study was to assess the efficacy of a qualitative grading
      system as seen on magnetic resonance imaging (MRI) as a tool in the management of
      multilevel LSS. OVERVIEW OF LITERATURE: LSS diagnosis is clinical but is usually
      radiologically supplemented. However, there are often multilevel radiological
      findings with non-specific or atypical clinical features. We used a qualitative
      grading system to help in the decision-making process of the management of
      patients with multilevel LSS. METHODS: 80 patients with LSS were treated with
      decompression and prospectively followed-up for a minimum of 12 months. All had
      failed conservative treatment. Qualitative grading of LSS severity was based on
      the dural sac in T2 weighted axial MRI images at all disc levels and was done
      from L1-2 to L5-S1 (n=400). Functional outcome was assessed using the Oswestry
      disability index (ODI). RESULTS: The mean patient age was 56.6 years, with a
      gender ratio of 0.6:1. Forty patients had degenerative LSS and 40 had
      degenerative spondylolysthesis. A total of 178 levels were decompressed, the
      majority of which were L4-L5 (43.82%), followed by L5-S1 (41.57%). According to
      our qualitative grading system, grade D stenosis (53.93%) was decompressed most
      frequently, followed by grade C stenosis (41.57%). The average preoperative ODI
      score was 58.55%, which later reduced to 19.15%. Seventy percent of patients
      achieved excellent results, whereas 30% achieved good results. CONCLUSIONS:
      Morphological grading is a useful tool in decision making in surgery for
      multilevel LSS. Grade C and D stenosis should be decompressed, whereas A and B
      should not be, unless clinically justified.

PMID- 28443174
TI  - Clinical and Radiological Outcomes after Microscopic Bilateral Decompression via
      a Unilateral Approach for Degenerative Lumbar Disease: Minimum 5-Year Follow-Up.
AB  - STUDY DESIGN: A retrospective study. PURPOSE: To assess postoperative bone
      regrowth at surgical sites after lumbar decompression with >5 years of follow-up.
      Postoperative preservation of facet joints and segmental spinal instability
      following surgery were also evaluated. OVERVIEW OF LITERATURE: Previous reports
      have documented bone regrowth after conventional laminectomy or laminotomy and
      several factors associated with new bone formation. METHODS: Forty-nine patients
      who underwent microscopic bilateral decompression via a unilateral approach at L4
      5 were reviewed. Primary outcomes included correlations among postoperative bone
      regrowth, preservation of facet joints, radiographic parameters, and clinical
      outcomes. Secondary outcomes included comparative analyses of radiographic
      parameters and clinical outcomes among preoperative diagnoses (lumbar spinal
      stenosis, degenerative spondylolisthesis, and degenerative lumbar scoliosis).
      RESULTS: The average value of bone regrowth at the latest follow-up was
      significantly higher on the dorsal side of the facet joint (3.4 mm) than on the
      ventral side (1.3 mm). Percent facet joint preservation was significantly smaller
      on the approach side (79.2%) than on the contralateral side (95.2%). Bone
      regrowth showed a significant inverse correlation with age, but no significant
      correlation was observed with facet joint preservation, gender, postoperative
      segmental spinal motion, or clinical outcomes. Subanalysis of these data revealed
      that bone regrowth at the latest follow-up was significantly greater in patients
      with degenerative lumbar scoliosis than in those with lumbar spinal stenosis.
      Postoperative segmental spinal motion at L4-L5 did not progress significantly in
      patients with degenerative spondylolisthesis or degenerative lumbar scoliosis
      compared with those with lumbar spinal stenosis. CONCLUSIONS: Microscopic
      bilateral decompression via a unilateral approach prevents postoperative spinal
      instability because of satisfactory preservation of facet joints, which may be
      the primary reason for inadequate bone regrowth. Postoperative bone regrowth was
      not related to clinical outcomes and postoperative segmental spinal instability.

PMID- 28443175
TI  - The Versatile Approach: A Novel Single Incision Combined with Anterior and
      Posterior Approaches for Decompression and Instrumented Fusion to Treat
      Tuberculosis of the Thoracic Spine.
AB  - STUDY DESIGN: Retrospective case series. PURPOSE: To describe a novel single
      incision that combines anterior and posterior approaches for decompression and
      instrumented fusion to treat tuberculosis of the thoracic spine and study the
      neurological and radiological outcomes. OVERVIEW OF LITERATURE: Tuberculosis of
      the spine remains a major health issue in many developing countries. The options
      for treating tuberculosis of the thoracic spine include the anterior, posterior,
      and combined approaches, each with its advantages and disadvantages. METHODS:
      Totally, 143 patients with tuberculosis of the thoracic spine were surgically
      treated using the "Versatile approach". Posterior fixation was performed using
      sublaminar wires and a Hartshill rectangle in all patients. Anterior
      reconstruction was accomplished using bone graft harvested from autologous rib,
      iliac crest, or fibula. RESULTS: The study included 45 males and 98 females, with
      a mean age of 33.18+/-18.65 years (range, 3-82 years) and a mean follow-up of
      60.23+/-24.56 months (range, 18-156 months). Kyphosis improved from a mean value
      of 24.02 preoperatively to 10.25 postoperatively. A preoperative neurological
      deficit was observed in 131 patients, with 130 patients regaining ambulatory
      power. No patient had deterioration of neurological status following surgery.
      Fusion was achieved in all cases. The visual analogscale score improved from an
      average score of 7.02 preoperatively to 1.51 at final follow-up. Eight patients
      had superficial macerations, which healed spontaneously. One patient had buckling
      of the anterior graft, and one patient had implant breakage following road
      traffic accident. CONCLUSIONS: The "Versatile approach" is an effective, single
      stage, single-incision method that combines anterior and posterior approaches for
      the surgically treating tuberculosis of the thoracic spine. It offers the
      advantage of direct visualization for decompression and reconstruction of the
      anterior and posterior vertebral columns, thus providing an excellent, long
      lasting clinical outcome.

PMID- 28443176
TI  - One-Stage Anterolateral Debridement, Bone Grafting, and Internal Fixation for
      Treating Lumbosacral Tuberculosis.
AB  - STUDY DESIGN: Retrospective case series. PURPOSE: To investigate the clinical
      efficacy and feasibility of one-stage anterolateral debridement, bone grafting,
      and internal fixation for treating lumbosacral tuberculosis. OVERVIEW OF
      LITERATURE: There has been no consensus regarding the optimal means of treating
      lumbosacral tuberculosis. The one-stage anterolateral extraperitoneal approach
      for radical debridement, bone grafting, and internal fixation for treating
      lumbosacral tuberculosis is rare in literature. METHODS: Twenty-one patients with
      lumbosacral tuberculosis were retrospectively analyzed. All patients underwent
      the surgery of anterolateral debridement after regularly antituberculous drugs
      therapy. We evaluated the erythrocyte sedimentation rate, C-reactive protein,
      radiography, computed tomography, magnetic resonance imaging, visual analogue
      score, and Oswestry disability index before and after surgery. RESULTS: All
      patients completed a follow-up survey 9-48 months after surgery. All patients'
      wounds healed well without chronic infection or sinus formation, and all patients
      with low-back pain reported relief after surgery. All cases had no tuberculosis
      recurrence. Solid bony fusion was achieved within 6-12 months. At final follow
      up, evaluated the erythrocyte sedimentation rate decreased from 38.1+/-12.5 to
      11.3+/-7.1 mm/hr, C-reactive protein decreased from 6.2+/-4.2 to 1.6+/-1.3 mg/dL,
      the visual analog scale score decreased from 4.6+/-1.1 to 1.4+/-1.0, the Oswestry
      disability index score decreased from 50.2%+/-11.9% to 13.0%+/-6.6%, and the
      lumbosacral angle increased from 20.0 degrees +/-4.8 degrees  to 29.0 degrees +/
      3.9 degrees  (p<0.05). CONCLUSIONS: One-stage anterolateral debridement, bone
      grafting, and internal instrument fixation for treating lumbosacral tuberculosis
      is safe and effective.

PMID- 28443177
TI  - Atlantoaxial Stabilization Using C1 and C2 Laminar Screw Fixation.
AB  - We describe the use of a C1 laminar screw in combination with a C2 laminar screw
      as a salvage technique to treat two patients, one with persistent first
      intersegmental artery and the other with vertebral artery occlusion after
      cervical spine fracture. The combined use of C1 and C2 laminar screws allows for
      good fixation of the atlantoaxial joint with a lower risk of vertebral artery
      injury; therefore, it can be an alternative surgical procedure for patients with
      congenital or traumatic anomalous vertebral artery.

PMID- 28443178
TI  - Driving Safety after Spinal Surgery: A Systematic Review.
AB  - This study aimed to assess driving reaction times (DRTs) after spinal surgery to
      establish a timeframe for safe resumption of driving by the patient
      postoperatively. The MEDLINE and Google Scholar databases were analyzed according
      to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
      Analysis) Statement for clinical studies that investigated changes in DRTs
      following cervical and lumbar spinal surgery. Changes in DRTs and patients'
      clinical presentation, pathology, anatomical level affected, number of spinal
      levels involved, type of intervention, pain level, and driving skills were
      assessed. The literature search identified 12 studies that investigated
      postoperative DRTs. Six studies met the inclusion criteria; five studies assessed
      changes in DRT after lumbar spine surgery and two studies after cervical spina
      surgery. The spinal procedures were selective nerve root block, anterior cervical
      discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited
      variable responses to spinal surgery and depended on the patients' clinical
      presentation, spinal level involved, and type of procedure performed. The
      evidence regarding the patients' ability to resume safe driving after spinal
      surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal
      intervention level is a widely accepted indicator for safe driving, with variable
      levels of statistical significance owing to multiple confounding factors.
      Considerations of the type of spinal intervention, pain level, opioid
      consumption, and cognitive function should be factored in the assessment of a
      patient's ability to safely resume driving.

PMID- 28443179
TI  - Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic
      Chemicals in Relation to Antimutagenicity and Anticarcinogenicity.
AB  - A variety of xenobiotic chemicals, such as polycyclic aromatic hydrocarbons
      (PAHs), aryl- and heterocyclic amines and tobacco related nitrosamines, are
      ubiquitous environmental carcinogens and are required to be activated to
      chemically reactive metabolites by xenobiotic-metabolizing enzymes, including
      cytochrome P450 (P450 or CYP), in order to initiate cell transformation. Of
      various human P450 enzymes determined to date, CYP1A1, 1A2, 1B1, 2A13, 2A6, 2E1,
      and 3A4 are reported to play critical roles in the bioactivation of these
      carcinogenic chemicals. In vivo studies have shown that disruption of Cyp1b1 and
      Cyp2a5 genes in mice resulted in suppression of tumor formation caused by 7,12
      dimethylbenz[a]anthracene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone,
      respectively. In addition, specific inhibitors for CYP1 and 2A enzymes are able
      to suppress tumor formation caused by several carcinogens in experimental animals
      in vivo, when these inhibitors are applied before or just after the
      administration of carcinogens. In this review, we describe recent progress,
      including our own studies done during past decade, on the nature of inhibitors of
      human CYP1 and CYP2A enzymes that have been shown to activate carcinogenic PAHs
      and tobacco-related nitrosamines, respectively, in humans. The inhibitors
      considered here include a variety of carcinogenic and/or non-carcinogenic PAHs
      and acethylenic PAHs, many flavonoid derivatives, derivatives of naphthalene,
      phenanthrene, biphenyl, and pyrene and chemopreventive organoselenium compounds,
      such as benzyl selenocyanate and benzyl selenocyanate; o-XSC, 1,2-, 1,3-, and 1,4
      phenylenebis( methylene)selenocyanate.

PMID- 28435662
TI  - Crafting minds and communities with Minecraft.
AB  - Minecraft is a first-person perspective video game in which players roam freely
      in a large three-dimensional environment. Players mine the landscape for minerals
      and use these minerals to create structures ( e.g., houses) and mould the
      landscape. But can Minecraft be used to craft communities and minds? In this
      opinion piece, we highlight the enormous potential of Minecraft for fostering
      social connectedness, collaboration, and its potential as an educational tool. We
      highlight the recent use of Minecraft to aid socialization in individuals with
      Autistic Spectrum Disorder (ASD) and promote civic engagement via the United
      Nations Human Settlement Program. We further provide novel links between
      Minecraft and recent on work on the role of social cures and community
      empowerment in enhancing mental health, wellbeing, and resilience.

PMID- 28443180
TI  - Terpenes from Forests and Human Health.
AB  - Forest bathing has beneficial effects on human health via showering of forest
      aerosols as well as physical relaxation. Terpenes that consist of multiple
      isoprene units are the largest class of organic compounds produced by various
      plants, and one of the major components of forest aerosols. Traditionally,
      terpene-containing plant oil has been used to treat various diseases without
      knowing the exact functions or the mechanisms of action of the individual
      bioactive compounds. This review categorizes various terpenes easily obtained
      from forests according to their anti-inflammatory, anti-tumorigenic, or
      neuroprotective activities. Moreover, potential action mechanisms of the
      individual terpenes and their effects on such processes, which are described in
      various in vivo and in vitro systems, are discussed. In conclusion, the studies
      that show the biological effectiveness of terpenes support the benefits of forest
      bathing and propose a potential use of terpenes as chemotherapeutic agents for
      treating various human diseases.

PMID- 28443181
TI  - Development of a Test Method for the Evaluation of DNA Damage in Mouse
      Spermatogonial Stem Cells.
AB  - Although alternative test methods based on the 3Rs (Replacement, Reduction,
      Refinement) are being developed to replace animal testing in reproductive and
      developmental toxicology, they are still in an early stage. Consequently, we
      aimed to develop alternative test methods in male animals using mouse
      spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and
      optimized the in vitro comet assay in our previous study. This study aimed to
      verify the validity of in vitro tests involving mSSCs by comparing their results
      with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea
      (HU), which is known to chemically induce male reproductive toxicity. The 50%
      inhibitory concentration (IC50) value of HU was 0.9 mM, as determined by the MTT
      assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after
      HU administration increased significantly, compared to the control. Annexin V, PI
      staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to
      compare in vitro tests with in vivo tests, the same substances were administered
      to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200
      mg/kg/day as measured by clinical measures of reduction in sperm motility and
      testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay
      were also performed. The results of the test with C57BL/6 mice were similar to
      those with mSSCs for HU treatment. Finally, linear regression analysis showed a
      strong positive correlation between results of in vitro tests and those of in
      vivo. In conclusion, the present study is the first to demonstrate the effect of
      HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the
      results of the current study suggest that mSSCs could be a useful model to
      predict male reproductive toxicity.

PMID- 28435664
TI  - Age-specific acceleration in malignant melanoma.
AB  - Background: The overall incidence of melanoma has increased steadily for several
      years. The relative change in incidence at different ages has not been fully
      described.  Objective: To describe how incidence at different ages has changed
      over time and to consider what aspects of tumour biology may explain the observed
      pattern of change in incidence.  Methods: The slope of incidence vs age measures
      the acceleration of cancer incidence with age. We described the pattern of change
      over time in the overall incidence of melanoma, as well as in acceleration. We
      used data for males and females from 3 different countries in the 17 sequential 5
      year birth-cohort categories from 1895-99 to 1975-79, from which we derived the
      incidence patterns.  Results: Over time, there has been a tendency for the
      overall incidence of melanoma to increase and for the acceleration (slope) of the
      age-incidence curves to decline. The changing patterns of melanoma incidence and
      acceleration differ between males and females and between the countries analysed.
      Conclusions: The observed pattern in melanoma of rising incidence and declining
      acceleration occurs in other cancers in response to genetic knockouts of
      mechanisms that protect against cancer. Perhaps some protective mechanism with
      respect to melanoma may be less effective now than in the past, possibly because
      of more intense environmental challenges.

PMID- 28435667
TI  - Neuraxial opioids as analgesia in labour, caesarean section and hysterectomy: A
      questionnaire survey in Sweden.
AB  - Background: Neuraxial opioids improve labour analgesia and analgesia after
      caesarean section (CS) and hysterectomy. Undesirable side effects and
      difficulties in arranging postoperative monitoring might influence the use of
      these opioids. The aim of the present survey was to assess the use of intrathecal
      and epidural morphine in gynaecology and obstetrics in Sweden. Methods: A
      questionnaire was sent to all anaesthetic obstetric units in Sweden concerning
      the use and postoperative monitoring of morphine, sufentanil and fentanyl in
      spinal/epidural anaesthesia. Results: A total of 32 of 47 (68%) units responded
      representing 83% of annual CS in Sweden. In CS spinal anaesthesia, 20/32 units
      use intrathecal morphine, the most common dose of which was 100 MUg (17/21).
      Intrathecal fentanyl (10-20 MUg) was used by 21 units and sufentanil (2.5 -10
      MUg) by 9/32 of the responding units. In CS epidural anaesthesia, epidural
      fentanyl (50-100 MUg) or sufentanil (5-25 MUg) were commonly used (25/32), and
      12/32 clinics used epidural morphine, the majority of units used a 2 mg dose.
      Intrathecal morphine for hysterectomy was used by 20/30 units, with 200 MUg as
      the most common dose (9/32). Postoperative monitoring was organized in adherence
      to the National Guidelines; the patient is monitored postoperative care or an
      obstetrical ward over 2-6 hours and up-to 12 hours in an ordinary surgical ward.
      Risk of respiratory depression/difficult to monitor was a reason for not using
      intrathecal opioids. Conclusions: Neuraxial morphine is used widely in Sweden in
      CS and hysterectomy, but is still restricted in some units because of the concern
      for respiratory depression and difficulties in monitoring.

PMID- 28435665
TI  - A voltage-dependent fluorescent indicator for optogenetic applications,
      archaerhodopsin-3: Structure and optical properties from in silico modeling.
AB  - It was demonstrated in recent studies that some rhodopsins can be used in
      optogenetics as fluorescent indicators of membrane voltage. One of the promising
      candidates for these applications is archaerhodopsin-3. However, the fluorescent
      signal for wild-type achaerhodopsin-3 is not strong enough for real applications.
      Rational design of mutants with an improved signal is an important task, which
      requires both experimental and theoretical studies. Herein, we used a homology
      based computational approach to predict the three-dimensional structure of
      archaerhodopsin-3, and a Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid
      approach with high-level multireference ab initio methodology (SORCI+Q/AMBER) to
      model optical properties of this protein. We demonstrated that this methodology
      allows for reliable prediction of structure and spectral properties of
      archaerhodopsin-3. The results of this study can be utilized for computational
      molecular design of efficient fluorescent indicators of membrane voltage for
      modern optogenetics on the basis of archaerhodopsin-3.

PMID- 28443186
TI  - General guidelines for biomedical software development.
AB  - Most bioinformatics tools available today were not written by professional
      software developers, but by people that wanted to solve their own problems, using
      computational solutions and spending the minimum time and effort possible, since
      these were just the means to an end. Consequently, a vast number of software
      applications are currently available, hindering the task of identifying the
      utility and quality of each. At the same time, this situation has hindered
      regular adoption of these tools in clinical practice. Typically, they are not
      sufficiently developed to be used by most clinical researchers and practitioners.
      To address these issues, it is necessary to re-think how biomedical applications
      are built and adopt new strategies that ensure quality, efficiency, robustness,
      correctness and reusability of software components. We also need to engage end
      users during the development process to ensure that applications fit their needs.
      In this review, we present a set of guidelines to support biomedical software
      development, with an explanation of how they can be implemented and what kind of
      open-source tools can be used for each specific topic.

PMID- 28443187
TI  - Treatment with penicillin G and hydrocortisone reduces ALS-associated symptoms: a
      case series of three patients.
AB  - Three male Caucasian patients with ALS were admitted to the hospital due to
      progressive dysphagia and dysarthria. During two 21-day courses of penicillin G
      and hydrocortisone, these patients' dysphagia and dysarthria resolved. The
      patient's other ALS-associated symptoms also improved, including respiratory
      function, coordination, walking, and muscle strength. This is the first report of
      a treatment with a protocol for treating dysphagia, dysarthria, respiratory
      depression and other ALS-related symptoms. Furthermore, the observations are
      consistent with the recent hypothesis that the successful treatment of ALS
      symptoms with this treatment course in six patients with syphilitic ALS was not
      directly due to the treatment of syphilis; but that the administered penicillin G
      and/or hydrocortisone treated these patients' ALS symptoms due the off-target
      pharmacological activity of penicillin G and/or hydrocortisone. This report
      therefore underscores the need to evaluate the efficacy of this treatment course
      in a clinical trial.

PMID- 28443188
TI  - Intestinal Obstruction Induced by Peach Stone in Stenosis of Sigmoid Colon by
      adenocarcinoma: A case report and literature review.
AB  - INTRODUCTION: Intestinal obstruction is the second among the most frequent acute
      abdominal conditions of the non-traumatic surgical pathologies. It is Found in
      20% of patients admitted to the emergency care services with acute abdominal
      pain. It often results in high morbidity and mortality. PRESENTATION OF CASE: We
      report a case of a foreign body resulting in a colon obstruction, concomitant
      with the diagnosis of a sigmoid cancer in a 47-year-old female. DISCUSSION: There
      are only a few cases of Intestinal Obstruction Induced by Peach Stone in Stenosis
      of Sigmoid Colon by Adenocarcinoma reported in the world literature. Due to late
      diagnosis It has a high mortality rate. Vomiting and emesis, abdominal
      distention, dysphagia, colicky abdominal pain, failure to pass flatus and
      anorexia are clinical findings. The immediate treatment is importance for patient
      survival. CONCLUSION: Intestinal obstructions and perforations are rare
      conditions caused by the ingestion of foreign bodies. These conditions must be
      taken into consideration especially owing to differing diagnoses and previous
      pathologies concomitant with the ingestion of objects such as those described in
      the foregoing adenocarcinoma case.

PMID- 28443189
TI  - Intraoperative dislocation of the trial bipolar cup into the pelvis during
      bipolar hip arthroplasty - A case report.
AB  - INTRODUCTION: Bipolar hip arthroplasty is a good option for treating femoral neck
      fractures, although some contraindications have been indicated. We report a case
      of intraoperative dislocation of the trial bipolar cup into the pelvis during
      bipolar hip arthroplasty. CASE PRESENTATION: A 74-year-old woman underwent
      bipolar hip arthroplasty for a femoral neck fracture (AO31-B2). She was placed in
      a lateral decubitus position, and a direct lateral approach was used. During
      intraoperative trial reduction, the trial bipolar cup became disengaged and
      dislocated into the anterior space of hip joint. Several attempts to retrieve it
      failed. The permanent femoral component was inserted, and the wound was closed.
      The patient was repositioned supine to allow an ilioinguinal approach, and the
      component was easily removed. She had an uneventful, good recovery. DISCUSSION:
      Several cases of intraoperative dislocation of the femoral trial head during
      total hip arthroplasty have been reported, this is the first report of
      dislocation of a bipolar trial cup. A previous report described difficulty
      retrieving a trial cup. CONCLUSION: We easily removed our trial cup using another
      approach. It is vital to plan systematically for this frustrating complication.

PMID- 28443190
TI  - First description of an Anaerobiospirillum succiniciproducens prosthetic joint
      infection.
AB  - Anaerobiospirillum succiniciproducens belongs to the normal flora of cats and
      dogs and can rarely infect humans. Here, we report the first case of an A.
      succiniciproducens prosthetic joint infection.

PMID- 28443191
TI  - The next generation of medical physicists.

PMID- 28443192
TI  - The determination of a dose deposited in reference medium due to (p,n) reaction
      occurring during proton therapy.
AB  - AIM: The aim of the investigation was to determine the undesirable dose coming
      from neutrons produced in reactions (p,n) in irradiated tissues represented by
      water. BACKGROUND: Production of neutrons in the system of beam collimators and
      in irradiated tissues is the undesirable phenomenon related to the application of
      protons in radiotherapy. It makes that proton beams are contaminated by neutrons
      and patients receive the undesirable neutron dose. MATERIALS AND METHODS: The
      investigation was based on the Monte Carlo simulations (GEANT4 code). The
      calculations were performed for five energies of protons: 50 MeV, 55 MeV, 60 MeV,
      65 MeV and 75 MeV. The neutron doses were calculated on the basis of the neutron
      fluence and neutron energy spectra derived from simulations and by means of the
      neutron fluence-dose conversion coefficients taken from the ICRP dosimetry
      protocol no. 74 for the antero-posterior irradiation geometry. RESULTS: The
      obtained neutron doses are much less than the proton ones. They do not exceed
      0.1%, 0.4%, 0.5%, 0.6% and 0.7% of the total dose at a given depth for the
      primary protons with energy of 50 MeV, 55 MeV, 60 MeV, 65 MeV and 70 MeV,
      respectively. CONCLUSIONS: The neutron production takes place mainly along the
      central axis of the beam. The maximum neutron dose appears at about a half of the
      depth of the maximum proton dose (Bragg peak), i.e. in the volume of a healthy
      tissue. The doses of neutrons produced in the irradiated medium (water) are about
      two orders of magnitude less than the proton doses for the considered range of
      energy of protons.

PMID- 28443193
TI  - Dose gradient based algorithm for beam weights selection in 3D-CRT plans.
AB  - AIM: In this work we test the usage of dose gradient based algorithm for the
      selection of beam weights in 3D-CRT plans for different cancer locations. Our
      algorithm is easy to implement for three fields technique with wedges defined by
      planner. BACKGROUND: 3D-CRT is usually realized with forward planning which is
      quite time consuming. Several authors published a few methods of beams weights
      optimization applicable to the 3D-CRT. MATERIALS AND METHODS: Optimization is
      based on an assumption that the best plan is achieved if dose gradient at ICRU
      point is equal to zero. Method was tested for 120 patients, treated in our clinic
      in 2011-2012, with different cancer locations. For each patient, three fields
      conformal plan (6 MV and 15 MV X-ray) with the same geometry as proposed by
      experienced planners was prepared. We compared dose distributions achieved with
      the proposed method and those prepared by experienced planners. The homogeneity
      of dose distributions was compared in terms of STD and near minimum and near
      maximum doses in the PTV. RESULTS: Mean difference of STD obtained by the
      proposed algorithm and by planners was 0.1%: 0.1% for prostate cancer, 0.3% for
      lung cancer, -0.1% for esophagus cancer, 0.1% for rectum cancer, -0.1% for
      gynecology cancer, -0.1% for stomach cancer. CONCLUSIONS: Applying the proposed
      algorithm leads to obtain the similar dose distribution homogeneity in the PTV as
      these achieved by planners and therefore can serve as a support in creating 3D
      CRT plans. It is also simple to use and can significantly speed up the treatment
      planning process.

PMID- 28443194
TI  - 68Ga-DOTA and analogs: Current status and future perspectives.
AB  - The construction of the 68Ge/68Ga generator has increased application of
      radiopharmaceuticals labeled with this isotope in medicine. 68Ga-PET is widely
      employed in the management of neuroendocrine tumors but favorable chemistry with
      tri- and tetraaza-ring molecules has opened wide range of 68Ga application in
      other fields of PET imaging. This review covers the radiopharmaceuticals labeled
      with gallium in molecular imaging and shows perspectives on the use of gallium-68
      as a substitute for technetium-99, fluorine-18 and carbon-11 in some
      applications.

PMID- 28443195
TI  - Synthesis, quality control and determination of metallic impurities in 18F
      fludeoxyglucose production process.
AB  - AIM: The aim of this study was to synthesize 18FDG in some consecutive runs and
      check the quality of manufactured radiopharmaceuticals and to determine the
      distribution of metallic impurities in the synthesis process. BACKGROUND: For
      radiopharmaceuticals the general requirements are listed in European Pharmacopeia
      and these parameters have to be checked before application for human use.
      MATERIALS AND METHODS: Standard methods for the determination of basic
      characteristics of radiopharmaceuticals were used. Additionally, high resolution
      gamma spectrometry was used for the assessment of nuclidic purity and inductively
      coupled plasma with mass spectrometry to evaluate metallic content. RESULTS:
      Results showed sources and distribution of metallic and radiometallic impurities
      in the production process. Main part is trapped in the initial separation column
      of the synthesis unit and is not distributed to the final product in significant
      amounts. CONCLUSIONS: Produced 18FDG filled requirements of Ph.Eur. and the
      content of radionuclidic and metallic impurities was in the acceptable range.

PMID- 28443196
TI  - Beam monitor detectors for medical applications.
AB  - Beam monitoring is fundamental for any particle accelerator. In particular, it is
      a crucial issue in medical applications of particle physics due to the required
      high precision and reliability. Radioisotope production and cancer radiotherapy
      require specific beam monitor detectors. In this paper, three recently designed
      instruments are reviewed. One of them is a newly designed beam monitor detector
      based on doped silica and optical fibres. It represents a promising solution.
      This apparatus can be used with various types of beams and for both hadrontherapy
      and radioisotope production. For this reason, a more detailed description of this
      multipurpose detector is provided.

PMID- 28443197
TI  - Investigation of the bystander effect in CHO-K1 cells.
AB  - AIM: Investigation of the bystander effect in Chinese Hamster Ovary cells (CHO
      K1) co-cultured with cells irradiated in the dose range of 0.1-4 Gy of high LET
      12C ions and X-rays. BACKGROUND: The radiobiological effects of charged heavy
      particles on a cellular or molecular level are of fundamental importance in the
      field of biomedical applications, especially in hadron therapy and space
      radiation biology. MATERIALS AND METHODS: A heavy ion 12C beam from the Heavy Ion
      Laboratory of the University of Warsaw (HIL) was used to irradiate CHO-K1 cells.
      Cells were seeded in Petri dishes specially designed for irradiation purposes.
      Immediately after irradiation, cells were transferred into transwell culture
      insert dishes to enable co-culture of irradiated and non-irradiated cells. Cells
      from the membrane and well shared the medium but could not touch each other. To
      study bystander effects, a clonogenic survival assay was performed. RESULTS: The
      survival fraction of cells co-cultured with cells irradiated with 12C ions and X
      rays was not reduced. CONCLUSIONS: The bystander effect was not observed in these
      studies.

PMID- 28443198
TI  - Status report: Nanodosimetry of carbon ion beam at HIL.
AB  - We present preliminary data for measured distributions of ionization cluster size
      produced by carbon ions in tissue equivalent media. The experiments were carried
      out with a beam of 92 MeV carbon ions from the U200p cyclotron at the Heavy Ion
      Laboratory (HIL), University of Warsaw, and nitrogen targets using the so-called
      Jet Counter set-up.

PMID- 28443199
TI  - Overdiagnosis of breast cancer in population screening: does it make breast
      screening worthless?
AB  - The risk of breast cancer (BC) overdiagnosis attributed to mammography screening
      is an unresolved issue, complicated by heterogeneity in the methodology of
      quantifying its magnitude, and both political and scientific elements surrounding
      interpretation of the evidence on this phenomenon. Evidence from randomized
      trials and also from observational studies shows that mammography screening
      reduces the risk of BC death; similarly, these studies provide sufficient
      evidence that overdiagnosis represents a serious harm from population breast
      screening. For both these outcomes of screening, BC mortality reduction and
      overdiagnosis, estimates of magnitude vary between studies however overdiagnosis
      estimates are associated with substantial uncertainty. The trade-off between the
      benefit and the collective harms of BC screening, including false-positives and
      overdiagnosis, is more finely balanced than initially recognized, however the
      snapshot of evidence presented on overdiagnosis does not mean that breast
      screening is worthless. Future efforts should be directed towards (a) ensuring
      that any changes in the implementation of BC screening optimize the balance
      between benefit and harms, including assessing how planned or actual changes
      modify the risk of overdiagnosis; (b) informing women of all the outcomes that
      may affect them when they participate in screening using well-crafted and
      balanced information; and

PMID- 28443201
TI  - Epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in
      China.
AB  - Esophageal cancer is one of the most fatal diseases worldwide mainly because of
      its rapid progression and poor prognosis. Although the incidence of esophageal
      adenocarcinoma has markedly risen in North America and Europe in the past several
      decades, esophageal squamous cell carcinoma is still the predominant subtype of
      esophageal cancer, especially in China. It accounts for more than 90% of all
      esophageal squamous cell carcinoma cases in China. Geographical differentiation
      is one of the most distinctive characteristics of esophageal cancer. The
      progression, risk factors, and prognosis of these two subtypes of esophageal
      cancer differ. This study reviews the epidemiology, etiology, and prevention of
      esophageal squamous cell carcinoma in China, thereby providing systematic
      references for policy-makers who will decide on issues of esophageal cancer
      prevention and control.

PMID- 28443202
TI  - DNA methylation assay for colorectal carcinoma.
AB  - Colorectal carcinoma (CRC) is a common cause of morbidity and mortality
      worldwide. Two pathogenic pathways are involved in the development of adenoma to
      CRC. The first pathway involvesAPC/beta-catenin characterized by chromosomal
      instability resulting in the accumulation of mutations. The second pathway is
      characterized by lesions inDNA mismatch repair genes. Aberrant DNA methylation in
      selected gene promoters has emerged as a new epigenetic pathway in CRC
      development. CRC screening is the most efficient strategy to reduce death.
      Specific DNA methylation events occur in multistep carcinogenesis. Epigenetic
      gene silencing is a causative factor of CRC development. DNA methylations have
      been extensively examined in stool from CRC and precursor lesions. Many
      methylated genes have been described in CRC and adenoma, although no definite DNA
      methylation biomarkers panel has been established. Multiple DNA methylation
      biomarkers, including secreted frizzled-related protein 2, secreted frizzled
      related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine
      DNA methyltransferase, have been further investigated, and observations have
      revealed that DNA methylation biomarkers exhibit with high sensitivity and
      specificity. These markers may also be used to diagnose CRC and adenoma in early
      stages. Real time polymerase chain reaction (qPCR) is sensitive, scalable,
      specific, reliable, time saving, and cost effective. Stool exfoliated markers
      provide advantages, including sensitivity and specificity. A stool qPCR
      methylation test may also be an enhanced tool for CRC and adenoma screening.

PMID- 28443203
TI  - Epidemic trend, screening, and early detection and treatment of cancer in Chinese
      population.
AB  - Epidemiological studies showed the incidence mortality rates of cancer were
      increasing in recent decades in Chinese population. National and regional
      preventive programs aim to reduce the health hazards of cancer and focuse the
      population at high risks for specific cancer, particularly in rural areas and to
      offer the access to early detection for multlple cancers in urban areas. The
      early screening, early detection and treatment have been put into operation for
      the population at risks in rural areas at first, and in the urban areas in recent
      years. To understand the epidemic patterns and trends of cancer, and the
      experiences in applying early detection strategies in China, selected literatures
      were reviewed for brief summary.

PMID- 28443204
TI  - Association of genotypes of rs671 withinALDH2 with risk for gastric cardia
      adenocarcinoma in the Chinese Han population in high- and low-incidence areas.
AB  - OBJECTIVE: : This study aimed to determine if gastric cardia adenocarcinoma (GCA)
      risk was associated with the lys (A or *2) allele at the rs671 (glu504lys)
      polymorphism within the aldehyde dehydrogenase 2 (ALDH2) gene in a Chinese Han
      population. We also aimed to investigateALDH2 genotypic distributions between
      subjects from high- and low-incidence areas for both GCA and esophageal squamous
      cell carcinoma (ESCC). METHODS: : We designed a case-control study including
      2,686 patients with GCA and 3,675 control subjects from high- and low-incidence
      areas for both GCA and ESCC in China. TaqMan allele discrimination assay was used
      to genotype the rs671 polymorphism.chi2 test and binary logistic regression
      analysis were used to estimate the odds ratios for the development of GCA, and
      multivariate ordinal logistic regression was used to analyzeALDH2 genotypic
      distributions among different groups. RESULTS: : Compared withALDH2*1/*1
      homozygotes,ALDH2*1/*2 andALDH2*2/*2 carriers did not increase the risk for GCA
      in the Chinese Han population (P>0.05). Interestingly, the ratio of homozygous or
      heterozygousALDH2 *2 carriers in high-incidence areas for both GCA and ESCC was
      lower than that in low-incidence areas (P<0.001). CONCLUSIONS: : Genotypes of
      rs671 atALDH2 may not increase GCA susceptibility in Chinese Han populations. In
      addition, theALDH2 genotypic distribution differs between Chinese Han populations
      from high- and low-incidence areas for both GCA and ESCC. Our findings may shed
      light on the possible genetic mechanism for the dramatic geographic differences
      of GCA occurrence in China.

PMID- 28443206
TI  - Estimation of lung cancer burden in Australia, the Philippines, and Singapore: an
      evaluation of disability adjusted life years.
AB  - OBJECTIVE: Lung cancer is one of the leading cancers and major causes of cancer
      mortality worldwide. The economic burden associated with the high mortality of
      lung cancer is high, which accounts for nearly $180 billion on a global scale in
      2008. This paper aims to understand the economic burden of lung cancer in terms
      of disability adjusted life years (DALY) in Australia, the Philippines, and
      Singapore. METHODS: The years of life lost (YLL) and years lost due to disability
      (YLD) were calculated using the formula developed by Murray and Lopez in 1996 as
      part of a comprehensive assessment of mortality and disability for diseases,
      injuries and risk factors in 1990 and projected to 2020. The same formula is
      represented in the Global Burden of Disease template provided by the World Health
      Organization. Appropriate assumptions were made when data were unavailable and
      projections were performed using regression analysis to obtain data for 2015.
      RESULTS: The total DALYs due to lung cancer in Australia, the Philippines, and
      Singapore were 91,695, 38,584, and 12,435, respectively, and the corresponding
      DALY rates per a population of 1,000 were 4.0, 0.4, and 2.2, respectively, with a
      discount rate of 3%. When researchers calculated DALYs without the discount rate,
      the burden of disease increased substantially; the DALYs were 117,438 in
      Australia, 50,977 in the Philippines, and 16,379 in Singapore. Overall, YLL or
      premature death accounted for more than 95% of DALYs in these countries.
      CONCLUSIONS: Strategies for prevention, early diagnosis, and prompt treatment
      must be devised for diseases where the major burden is due to mortality.

PMID- 28443205
TI  - A pilot study of radiologic measures of abdominal adiposity: weighty contributors
      to early pancreatic carcinogenesis worth evaluating?
AB  - OBJECTIVE: Intra-abdominal fat is a risk factor for pancreatic cancer (PC), but
      little is known about its contribution to PC precursors known as intraductal
      papillary mucinous neoplasms (IPMNs). Our goal was to evaluate quantitative
      radiologic measures of abdominal/visceral obesity as possible diagnostic markers
      of IPMN severity/pathology. METHODS: In a cohort of 34 surgically-resected,
      pathologically-confirmed IPMNs (17 benign; 17 malignant) with preoperative
      abdominal computed tomography (CT) images, we calculated body mass index (BMI)
      and four radiologic measures of obesity: total abdominal fat (TAF) area, visceral
      fat area (VFA), subcutaneous fat area (SFA), and visceral to subcutaneous fat
      ratio (V/S). Measures were compared between groups using Wilcoxon two-sample
      exact tests and other metrics. RESULTS: Mean BMI for individuals with malignant
      IPMNs (28.9 kg/m2) was higher than mean BMI for those with benign IPMNs (25.8
      kg/m2) (P=0.045). Mean VFA was higher for patients with malignant IPMNs (199.3
      cm2) compared to benign IPMNs (120.4 cm2),P=0.092. V/S was significantly higher
      (P=0.013) for patients with malignant versus benign IPMNs (1.25vs. 0.69 cm2),
      especially among females. The accuracy, sensitivity, specificity, and positive
      and negative predictive value of V/S in predicting malignant IPMN pathology were
      74%, 71%, 76%, 75%, and 72%, respectively. CONCLUSIONS: Preliminary findings
      suggest measures of visceral fat from routine medical images may help predict
      IPMN pathology, acting as potential noninvasive diagnostic adjuncts for
      management and targets for intervention that may be more biologically-relevant
      than BMI. Further investigation of gender-specific associations in larger,
      prospective IPMN cohorts is warranted to validate and expand upon these
      observations.

PMID- 28443200
TI  - Epidemiology of ovarian cancer: a review.
AB  - Ovarian cancer (OC) is the seventh most commonly diagnosed cancer among women in
      the world and the tenth most common in China. Epithelial OC is the most
      predominant pathologic subtype, with five major histotypes that differ in
      origination, pathogenesis, molecular alterations, risk factors, and prognosis.
      Genetic susceptibility is manifested by rare inherited mutations with high to
      moderate penetrance. Genome-wide association studies have additionally identified
      29 common susceptibility alleles for OC, including 14 subtype-specific alleles.
      Several reproductive and hormonal factors may lower risk, including parity, oral
      contraceptive use, and lactation, while others such as older age at menopause and
      hormone replacement therapy confer increased risks. These associations differ by
      histotype, especially for mucinous OC, likely reflecting differences in etiology.
      Endometrioid and clear cell OC share a similar, unique pattern of associations
      with increased risks among women with endometriosis and decreased risks
      associated with tubal ligation. OC risks associated with other gynecological
      conditions and procedures, such as hysterectomy, pelvic inflammatory disease, and
      polycystic ovarian syndrome, are less clear. Other possible risk factors include
      environmental and lifestyle factors such as asbestos and talc powder exposures,
      and cigarette smoking. The epidemiology provides clues on etiology, primary
      prevention, early detection, and possibly even therapeutic strategies.

PMID- 28443207
TI  - Truth telling for patients with esophageal squamous cell carcinoma in Henan,
      China.
AB  - OBJECTIVE: : This study aims to investigate the truth-telling status and the
      relevant factors of esophageal squamous cell carcinoma (ESCC) patients in Henan,
      China. METHODS: : A cross-sectional study from April to June 2015 using
      questionnaires was given to 301 family members of hospitalized ESCC patients
      based in three affiliated hospitals of Zhengzhou University (i.e., The First
      Hospital, The Second Hospital, and Tumor Hospital) and Anyang Tumor Hospital.
      RESULTS: : Among the 41.9% (126/301) hospitalized ESCC patients who knew of their
      true diagnoses, only 4.0% patients were informed by their corresponding
      responsible doctors, 39.7% by their family members, and 56.3% by themselves.
      Univariate analyses showed that disclosure of confirmed ESCC diagnosis to
      patients was correlated with gender, family history of cancer (FHC), education
      level, vocation, hospital administrative level, and attitudes of family members
      (P < 0.05). Furthermore, multivariate analysis indicated that attitude of family
      members was the most important and an independent factor for diagnosis
      disclosure. Those patients with a negative FHC, under-education, manual
      occupation, advanced stages, and hospitalized in municipal hospitals exhibited a
      low rate of truth telling. CONCLUSIONS: : Truth telling for ESCC patients in
      Henan is not prevalent and may be improved through consultation with family
      members, particularly for patients with a negative FHC, poor education, manual
      occupation, and advanced stages.

PMID- 28443209
TI  - Metformin prevents hormonal and metabolic disturbances and 1,2-dimethylhydrazine
      induced colon carcinogenesis in non-diabetic rats.
AB  - Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and
      metabolic levels of serum of non-diabetic male Wistar rats with 1,2
      dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were studied.
      Carcinogenesis in the animals was also observed. Rats with DMH-induced colon
      adenocarcinomas had elevated levels of serum glucose, insulin, insulin-like
      growth factor-1, total cholesterol, triglycerides, catalase, malonic dialdehyde,
      glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and
      decreased hemoglobin. Treatment with two doses of MF normalized majority of these
      changes in DMH-treated rats, whereas the drug was ineffective in rats without DMH
      treatment. The only exception was the decreased triglyceride levels in MF-treated
      rats. A 100 mg/kg dose of MF increased DMH-induced exophytic colon carcinomas and
      decreased endophytic tumors compared with untreated rats. Moreover, both MF doses
      increased DMH-induced and highly differentiated tumors and decreased the
      invasiveness of colon carcinomas compared with rats provided with DMH and water.
      Therefore, effects of MF on metabolic homeostasis are critical for preventing
      colon cancer.

PMID- 28443208
TI  - Roles of Rap1 signaling in tumor cell migration and invasion.
AB  - Ras-associated protein-1 (Rap1), a small GTPase in the Ras-related protein
      family, is an important regulator of basic cellular functions (e.g., formation
      and control of cell adhesions and junctions), cellular migration, and
      polarization. Through its interaction with other proteins, Rap1 plays many roles
      during cell invasion and metastasis in different cancers. The basic function of
      Rap1 is straightforward; it acts as a switch during cellular signaling
      transduction and regulated by its binding to either guanosine triphosphate (GTP)
      or guanosine diphosphate (GDP). However, its remarkably diverse function is
      rendered by its interplay with a large number of distinct Rap guanine nucleotide
      exchange factors and Rap GTPase activating proteins. This review summarizes the
      mechanisms by which Rap1 signaling can regulate cell invasion and metastasis,
      focusing on its roles in integrin and cadherin regulation, Rho GTPase control,
      and matrix metalloproteinase expression.

PMID- 28443210
TI  - Erratum to Bcl-2 expression is a poor predictor for hepatocellular carcinoma
      prognosis of andropause-age patients.

PMID- 28443211
TI  - Evaluation of common variants in MG53 and the risk of type 2 diabetes and insulin
      resistance in Han Chinese.
AB  - Abnormally increased skeletal-muscle-specific E3 ubiquitin ligase (MG53) is
      associated with the inhibition of insulin signalling and insulin resistance (IR)
      in animal models. Four community-based studies of Han Chinese populations were
      included in this study to test the association of variants of MG53 and type 2
      diabetes (T2D). The results showed that rs7186832 and rs12929077 in MG53 were
      significantly associated with T2D and impaired fasting glucose (IFG) of females
      in the discovery-stage case-control study and cohort study respectively of rural
      population but not in the replication sample of urban population. In rural
      population, the fasting insulin (mU/L) of the subjects with AA, AG and GG
      genotypes in rs12929077 were 8.70 +/- 8.05, 10.71 +/- 11.16 and 13.41 +/- 14.26,
      respectively, and increased linearly in T2D cases without medication treatment (P
      = 0.04). This variant was significantly associated with HOMA-IR (P = 0.020) and
      HOMA-IS (P = 0.023). In individuals with IFG, the insulin and HOMA-IR of AG
      carriers were significantly higher than those of AA carriers. In urban
      population, after glucose loading, there were significant differences in the 30
      min glucose, the area under the curve (AUC) of 30-min glucose and the AUC of 120
      min glucose according to the genotypes of rs7186832 and rs12929077 in males but
      not females. Our findings suggest that MG53 variants might confer risk
      susceptibility to the development of T2D of females and IR particularly in rural
      population.

PMID- 28443213
TI  - Synthesis and research of epoxy resin toughening agent.
AB  - In this paper, a synthesis method of epoxy resin toughening agent was presented,
      then the chemical composition and molecular number were studied, which include
      the DSC curves analysis, the fracture surface morphology and bonding strength. In
      addition, the mechanism of epoxy resin toughening agent and the effect of
      toughening agent's content to bonding strength were studied. The testing results
      reveal that this toughening agent can form a micro two-phase structure in epoxy
      amine system, which results in the stable chemical properties and excellent
      physical properties.

PMID- 28443212
TI  - Tooth replantation with adipose tissue stem cells and fibrin sealant: microscopic
      analysis of rat's teeth.
AB  - Treatment for dental avulsion cases is early or late replantation of the
      traumatized teeth. Prognosis of the replanted tooth depends on the level of
      periodontal injury. Adipose tissue stem cells (ATSCs) were reported to improve
      periodontal ligament tissue (PDL) regeneration. Fibrin sealant (FS) contains
      thrombin and fibrinogen to form an adhesive fibrin clot routinely used in
      surgical procedures. Here, we aimed to investigate the effects of ATSCs + FS
      treatment on healing of PDL after tooth replantation in a rat model. After 60 min
      of extraction, maxillary central incisor teeth were replanted with ATSCs + FS.
      Two months later, the rats were sacrificed and hemimaxilla blocks were dissected
      out for histological analysis. The results showed that there was a significant
      improvement in histological findings of ATSCs + FS treated group compared to only
      FS treated and non-treated groups corresponding to reduced inflammatory
      resorption and increased new PDL formation. Furthermore, the ankylosis levels
      were lowered after ATSCs + FS treatment. Singular use of FS improved PDL healing
      moderately. Our results indicated that ATSCs + FS treatment improves PDL healing
      after tooth replantation suggesting a new therapeutic potential in the treatment
      of dental avulsion cases.

PMID- 28443215
TI  - Wastewater treatment evaluation for enterprises based on fuzzy-AHP comprehensive
      evaluation: a case study in industrial park in Taihu Basin, China.
AB  - This paper applied the fuzzy comprehensive evaluation (FCE) technique and
      analytic hierarchy process (AHP) procedure to evaluate the wastewater treatment
      for enterprises. Based on the characteristics of wastewater treatment for
      enterprises in Taihu basin, an evaluating index system was established for
      enterprise and analysis hierarchy process method was applied to determine index
      weight. Then the AHP and FCE methods were combined to validate the wastewater
      treatment level of 3 representative enterprises. The results show that the
      evaluation grade of enterprise 1, enterprise 2 and enterprise 3 was middle, good
      and excellent, respectively. Finally, the scores of 3 enterprises were calculated
      according to the hundred-mark system, and enterprise 3 has the highest wastewater
      treatment level, followed by enterprise 2 and enterprises 1. The application of
      this work can make the evaluation results more scientific and accurate. It is
      expected that this work may serve as an assistance tool for managers of
      enterprise in improving the wastewater treatment level.

PMID- 28443214
TI  - Prevalence and risk factors of methicillin-resistant Staphylococcus aureus
      colonization among HIV patients in Mekelle, Northern Ethiopia.
AB  - HIV-positive individuals are at higher risk of Methicillin Resistant
      Staphylococcus aureus (MRSA) colonization and its related infection. There is
      limited data in the nation on the prevalence and risk factors of MRSA
      colonization among HIV patients. The aim of this study was to address the
      existing knowledge gap. Cross sectional study was carried out from September 2014
      to February 2015 in three selected health centers and one general hospital. A
      standardized questionnaire was developed for collection of socio-demographic and
      clinical data. A total of 498 Nasal and throat swabs (two for each patient) were
      collected from 249 patients, transported and processed using standard
      bacteriological procedures. Data was analyzed using Chi square (X2) test and
      associated risk factors were determined. P < 0.05 was considered statistically
      significant. Out of 249 study participants, S. aureus was isolated from 81 (32.5
      %) patients, with MRSA colonization rate of 6 (2.4 %). MRSA isolates were
      resistant to Ciprofloxacin and trimethoprim-sulphamethoxazole (16.7 % each),
      clindamycin (33.3 %) and erythromycin (50 %). However, all MRSA isolates were 100
      % sensitive to Amikacin. History of hospitalization, percutaneous device usage,
      patients with a household member's hospitalization and low CD4 count (<200
      cells/mm3) were significantly associated with S. aureus colonization (p < 0.05).

PMID- 28443216
TI  - Predictive control strategy of a gas turbine for improvement of combined cycle
      power plant dynamic performance and efficiency.
AB  - This paper presents a novel strategy for implementing model predictive control
      (MPC) to a large gas turbine power plant as a part of our research progress in
      order to improve plant thermal efficiency and load-frequency control performance.
      A generalized state space model for a large gas turbine covering the whole steady
      operational range is designed according to subspace identification method with
      closed loop data as input to the identification algorithm. Then the model is used
      in developing a MPC and integrated into the plant existing control strategy. The
      strategy principle is based on feeding the reference signals of the pilot valve,
      natural gas valve, and the compressor pressure ratio controller with the
      optimized decisions given by the MPC instead of direct application of the control
      signals. If the set points for the compressor controller and turbine valves are
      sent in a timely manner, there will be more kinetic energy in the plant to
      release faster responses on the output and the overall system efficiency is
      improved. Simulation results have illustrated the feasibility of the proposed
      application that has achieved significant improvement in the frequency variations
      and load following capability which are also translated to be improvements in the
      overall combined cycle thermal efficiency of around 1.1 % compared to the
      existing one.

PMID- 28443218
TI  - What Matters in the Performance of a Medial Institution?

PMID- 28443217
TI  - Malignant Peripheral Nerve Sheath Tumor of the C2 Nerve Root: Case Report.
AB  - Here we present the case of a 36-year-old man who was found to have a symptomatic
      malignant neural sheath tumor growing from the C2 nerve root following a period
      of progressively worsening headaches. The patient was successfully treated with
      surgical resection resulting in resolution of cranial nerve deficits. Though
      uncommon, malignant peripheral nerve sheath tumor must be considered in the
      differential diagnosis of tumors involving the cervical nerve roots and carotid
      space.

PMID- 28443219
TI  - Estimating Tuberculin Skin Test Reactions among Children and Teenagers Who
      Received the Bacillus Calmette-Guerin Vaccination at Birth: A Meta-analysis.
AB  - OBJECTIVES: Tuberculin skin reaction size is one indicator of bacillus Calmette
      Guerin (BCG) vaccine efficacy and a way to diagnose latent infection. Several
      primary studies have examined this issue. Combining the results of these studies
      using a meta-analysis will provide reliable evidence regarding this indicator for
      policymakers. This study aimed to estimate the total frequency of different
      tuberculin skin test reactions among Iranian children and teenagers who received
      the BCG vaccination at birth. METHODS: National and international databanks were
      searched using relevant keywords. After the search strategy was restricted and
      duplicates were excluded, the titles and abstracts of the remaining papers were
      screened. All included studies included healthy children who received the BCG
      vaccine without confirmed tuberculosis exposure. Heterogeneity of the results was
      assessed using the Cochrane test and I2 index showed the random effects model as
      the best model for estimating the pooled results. RESULTS: We combined the
      results of 14 primary studies including purified protein derivative reaction test
      measures of 26,281 Iranian children. The frequencies (95% confidence intervals)
      of the reactions were 8.5% (6.2-10.8) for patients with a reaction size >= 10 mm,
      29.9% (22.3-37.4) for a reaction size of 5-9 mm, and 60% (48.9-71.1) for a
      reaction size < 5 mm. CONCLUSION: Our study showed that large numbers of Iranian
      children and teens have no positive BCG vaccine reaction and a considerable
      number of children have been exposed to Mycobacterium tuberculosis.

PMID- 28443220
TI  - Do Factors Associated Self-rated Good Health and Their Influences Differ between
      Males and Females across Different Age Groups in Korean and Australia?
AB  - OBJECTIVES: This was a comparative study between Australia and Korea that
      investigated whether and to what extent factors related to self-rated good health
      (SRGH) differ by gender among age groups. METHODS: This study was a secondary
      analysis of data that were collected in nationally representative, cross
      sectional, and population-based surveys. We analyzed Australian and Korean
      participants > 20 years of age using 2011 data from the Australian National
      Nutritional Physical Activity Survey (n = 9,276) and the Korean National Health
      and Nutritional Examination Survey (n = 5,915). Analyses were based on multiple
      logistic regression after controlling for covariates. RESULTS: Factors associated
      with SRGH and the extent of their influence differed by gender among age groups
      within each nation. Australian SRGH was associated with more factors than Korean
      SRGH, except in participants > 65 years old. Many differences among adults aged
      20-44 years were observed, particularly with regard to the influence of
      socioeconomic factors. Living with a spouse only influenced SRGH in men 20-44
      years old in both countries, negatively for Korean men and positively for
      Australian men. In this same age group, SRGH was positively influenced by
      employment and attainment of a higher education level in Australian men but not
      among Korean men; among women, income, but not education, affected SRGH in Korea,
      whereas in Australia, women were more influenced by education than by income.
      Lack of chronic disease had a strong influence on SRGH in both countries and was
      influential in all Australians and Koreans except those >= 65 years old.
      CONCLUSION: Broad features of society should be considered when discussing health
      and differences in associated factors and their influences. For focused public
      health interventions of population groups, it is also necessary to consider
      gender and age groups within social environments.

PMID- 28443221
TI  - Knowledge Management Enablers and Process in Hospital Organizations.
AB  - OBJECTIVES: This research aimed to investigate the effects of knowledge
      management enablers, such as organizational structure, leadership, learning,
      information technology systems, trust, and collaboration, on the knowledge
      management process of creation, storage, sharing, and application. METHODS: Using
      data from self-administered questionnaires in four Korean tertiary hospitals,
      this survey investigated the main organizational factors affecting the knowledge
      management process in these organizations. A total of 779 questionnaires were
      analyzed using SPSS 18.0 and AMOS 18.0. RESULTS: The results showed that
      organizational factors affect the knowledge management process differently in
      each hospital organization. CONCLUSION: From a managerial perspective, the
      implications of these factors for developing organizational strategies that
      encourage and foster the knowledge management process are discussed.

PMID- 28443222
TI  - Analysis of Hospital Volume and Factors Influencing Economic Outcomes in Cancer
      Surgery: Results from a Population-based Study in Korea.
AB  - OBJECTIVES: To evaluate associations between hospital volume, costs, and length
      of stay (LOS), and clinical and demographic outcome factors for five types of
      cancer resection. The main dependent variables were cost and LOS; the primary
      independent variable was volume. METHODS: Data were obtained from claims
      submitted to the Korean National Health Insurance scheme. We identified patients
      who underwent the following surgical procedures: pneumonectomy, colectomy,
      mastectomy, cystectomy, and esophagectomy. Hospital volumes were divided into
      quartiles. RESULTS: Independent predictors of high costs and long LOS included
      old age, low health insurance contribution, non-metropolitan residents, emergency
      admission, Charlson score > 2, public hospital ownership, and teaching hospitals.
      After adjusting for relevant factors, there was an inverse relationship between
      volume and costs/LOS. The highest volume hospitals had the lowest procedure costs
      and LOS. However, this was not observed for cystectomy. CONCLUSION: Our findings
      suggest an association between patient and clinical factors and greater costs and
      LOS per surgical oncologic procedure, with the exception of cystectomy. Yet,
      there were no clear associations between hospitals' cost of care and risk
      adjusted mortality.

PMID- 28443223
TI  - Detection of Integrons and Staphylococcal Cassette Chromosome mec Types in
      Clinical Methicillin-resistant Coagulase Negative Staphylococci Strains.
AB  - OBJECTIVES: Integrons are thought to play an important role in the spread of
      antibiotic resistance. This study investigates class 1 and 2 integron-positive
      methicillin-resistant coagulase-negative staphylococci strains isolated in Iran
      and characterizes their patterns of antimicrobial resistance. METHODS: Hundred
      clinical isolates of coagulase-negative staphylococci were characterized for
      integron content and staphylococcal cassette chromosome mec (SCCmec) type.
      RESULTS: Sixteen isolates carried class 1 (intI1) integrons and four isolates
      carried class 2 (intI2) integrons. One resistance gene array was identified among
      the class 1 integrons (aadA1 cassette). The distribution of SCCmec types in 50
      methicillin-resistant coagulase-negative staphylococci strains showed that SCCmec
      types III and V dominated among the tested strains. CONCLUSION: This is the first
      report of methicillin-resistant coagulase-negative staphylococci strains that
      carry two mobile genetic elements, including class 1 and 2 integrons and SCCmec,
      in Iran.

PMID- 28443224
TI  - The Effect of Lactobacillus acidophilus PTCC 1643 on Cultured Intestinal
      Epithelial Cells Infected with Salmonella enterica serovar Enteritidis.
AB  - OBJECTIVES: Gastrointestinal disorders caused by Salmonella enterica serovar
      Enteritidis (SesE) are a significant health problem around the globe. Probiotic
      bacteria have been shown to have positive effects on the immune responses.
      Lactobacillus acidophilus was examined for its capability to influence the innate
      immune response of HT29 intestinal epithelial cells towards SesE. The purpose of
      this work was to assess the effect of L. acidophilus PTCC 1643 on cultured
      intestinal epithelial cells infected with SesE. METHODS: HT29 cells were cultured
      in Roswell Park Memorial Institute medium supplemented with 10% fetal bovine
      serum and 1% penicillin/streptomycin. The cells were treated with L. acidophilus
      PTCC 1643 after or before challenge with SesE. At 2 and 4 hours post-infection,
      we measured changes in the expression levels of TLR2 and TLR4 via real-time
      polymerase chain reaction. RESULTS: Treatment with L. acidophilus inhibited SesE
      induced increases in TLR2 and TLR4 expression in the infected HT29 cells.
      Moreover, the expression of TLR2 and TLR4 in cells that were pretreated with L.
      acidophilus and then infected with SesE was significantly higher than that in
      cells infected with SesE without pretreatment. Taken together, the results
      indicated that L. acidophilus had an anti-inflammatory effect and modulated the
      innate immune response to SesE by influencing TLR2 and TLR4 expression.
      CONCLUSION: Our findings suggested that L. acidophilus PTCC 1643 was able to
      suppress inflammation caused by SesE infection in HT29 cells and reduce TLR2 and
      TLR4 expression. Additional in vivo and in vitro studies are required to further
      elucidate the mechanisms underlying this anti-inflammatory effect.

PMID- 28443225
TI  - Analysis of Factors Affecting Women of Childbearing Age to Screen Using Visual
      Inspection with Acetic Acid.
AB  - OBJECTIVES: The purpose of this study was to evaluate patient factors such as
      knowledge, attitude, motivation, perception, socio-economic status and travel
      time to health facilities and assess how these factors affected patients'
      decision to pursue cervical cancer screening with visual inspection with acetic
      acid (VIA). METHODS: A total of 80 women of childbearing age who visited Kenjeran
      and Balongsari Public Health Centers for health assessments were involved in this
      study. Patients who agreed to participate in the study underwent a verbal
      questionnaire to evaluate various factors. RESULTS: Bivariate analysis concluded
      that knowledge, attitude, motivation, perception, socioeconomic status, and
      travel time to health facilities were significantly different between women who
      received VIA screening and women who did not receive VIA screening (p < 0.05).
      The factors of knowledge, attitudes, motivation, perception, socio-economic
      status, and the travel time to health facilities accounted for 2.920-fold, 2.043
      fold, 3.704-fold, 2.965-fold, 3.198-fold and 2.386-fold possibility,
      respectively, of patients to pursue cervical cancer screening with VIA.
      Multivariate analysis showed that perception, socio-economic status, and travel
      time to health facilities were the most important factors influencing whether or
      not women pursued VIA screening. CONCLUSION: Knowledge, attitude, motivation,
      perception, socio-economic status, and travel time to health facilities appears
      to affect women's' decision to pursue cervical cancer screening with VIA, with
      the largest intake being the motivational factor.

PMID- 28443226
TI  - A Novel PCR Assay for Detecting Brucella abortus and Brucella melitensis.
AB  - OBJECTIVES: Brucellosis is a major zoonotic disease that poses a significant
      public health threat worldwide. The classical bacteriological detection process
      used to identify Brucella spp. is difficult and time-consuming. This study aimed
      to develop a novel molecular assay for detecting brucellosis. METHODS: All
      complete sequences of chromosome 1 with 2.1-Mbp lengths were compared among all
      available Brucella sequences. A unique repeat sequence (URS) locus on chromosome
      1 could differentiate Brucella abortus from Brucella melitensis. A primer set was
      designed to flank the unique locus. A total of 136 lymph nodes and blood samples
      were evaluated and classified by the URS-polymerase chain reaction (PCR) method
      in 2013-2014. RESULTS: Biochemical tests and bacteriophage typing as the golden
      standard indicated that all Brucella spp. isolates were B. melitensis biovar 1
      and B. abortus biovar 3. The PCR results were the same as the bacteriological
      method for detecting Brucella spp. The sensitivity and specificity of the URS-PCR
      method make it suitable for detecting B. abortus and B. melitensis. CONCLUSION:
      Quick detection of B. abortus and B. melitensis can provide the most effective
      strategies for control of these bacteria. The advantage of this method over other
      presented methods is that both B. abortus and B. melitensis are detectable in a
      single test tube. Furthermore, this method covered 100% of all B. melitensis and
      B. abortus biotypes. The development of this URS-PCR method is the first step
      toward the development of a novel kit for the molecular identification of B.
      abortus and B. melitensis.

PMID- 28443227
TI  - Surveillance of Bacillus cereus Isolates in Korea from 2012 to 2014.
AB  - OBJECTIVES: To investigate the prevalence and toxin production characteristics of
      non-emetic and emetic Bacillus cereus strains isolated via the laboratory
      surveillance system in Korea. METHODS: A total of 667 B. cereus strains were
      collected by the Korea National Research Institute of Health laboratory
      surveillance system from 2012 to 2014. The collected strains were analyzed by
      geographical region, season, patient age, and patient sex. Additionally, the
      prevalence rates of enterotoxin and emetic toxin genes were evaluated. RESULTS:
      The isolation rate of B. cereus strains increased during the summer, but the
      isolation rate was evenly distributed among patient age groups. Emetic toxin was
      produced by 20.2% of the isolated strains. The prevalence rates of five
      enterotoxin genes (entFM, nheA, cytK2, hblC, and bceT) were 85.0, 78.6, 44.5,
      36.6, and 29.7%, respectively, among non-emetic strains and 77.8, 59.3, 17.8,
      11.9 and 12.6%, respectively, among emetic strains. Thus, the prevalence rates of
      all five enterotoxin genes were lower in emetic B. cereus. CONCLUSION: The
      prevalence of enterotoxin genes differed between non-emetic and emetic B. cereus
      strains. Among emetic B. cereus strains, the prevalence rates of two enterotoxin
      genes (cytK2 and hblC) were lower than those among the non-emetic strains. In
      both the emetic and non-emetic strains isolated in Korea, nheA and entFM were the
      most prevalent enterotoxin genes.

PMID- 28443228
TI  - Genome Sequencing Analysis of Atypical Shigella flexneri Isolated in Korea.
AB  - OBJECTIVES: An atypical Shigella flexneri strain with a plural agglutination
      pattern [i.e., reacting not only with serum samples containing type antigen II
      but also with serum samples containing group antigens (3)4 and 7(8)] was selected
      for genome sequencing, with the aim of obtaining additional comparative
      information about such strains. METHODS: The genomic DNA of atypical S. flexneri
      strain NCCP 15744 was sequenced using an Ion Torrent PGM sequencing machine (Life
      Technologies, USA). The raw sequence data were preprocessed and reference
      assembled in the CLC Assembly Cell software (version 4.0.6; CLC bio, USA).
      RESULTS: Ion Torrent sequencing produced 1,450,025 single reads with an average
      length of 144 bp, totaling ~209 Mbp. The NCCP 15744 genome is composed of one
      chromosome and four plasmids and contains a gtrX gene. Among the published genome
      sequences of S. flexneri strains, including 2457T, Sf301, and 2002017, strain
      NCCP 15744 showed high similarity with strain 2002017. The differences between
      NCCP 15744 and 2002017 are as follows: i) NCCP 15744 carries four plasmids
      whereas 2002017 carries five; ii) 19 genes (including CI, CII, and cro) were lost
      in the SHI-O genomic island of NCCP 15744 and six genes were gained as compared
      with strain 2002017. CONCLUSION: Strain NCCP 15744 is genetically similar to
      2002017, but these two strains have different multilocus sequence types and
      serotypes. The exact reason is unclear, but the 19 lost genes may be responsible
      for the atypical seroconversion of strain NCCP 15744.

PMID- 28443229
TI  - Emergence of Norovirus GII.17-associated Outbreak and Sporadic Cases in Korea
      from 2014 to 2015.
AB  - Human norovirus are major causative agent of nonbacterial acute gastroenteritis.
      In general, genogroup (G) II.4 is the most prominent major genotype that
      circulate in human population and the environment. However, a shift in genotypic
      trends was observed in Korea in December 2014. In this study, we investigated the
      trend of norovirus genotype in detail using the database of Acute Diarrhea
      Laboratory Surveillance (K-EnterNet) in Korea. GII.17 has since become a major
      contributor to outbreaks of norovirus-related infections and sporadic cases in
      Korea, although the reason for this shift remain unknown.

PMID- 28443230
TI  - Prediction of optimal gene functions for osteosarcoma using network-based- guilt
      by association method based on gene oncology and microarray profile.
AB  - In the current study, we planned to predict the optimal gene functions for
      osteosarcoma (OS) by integrating network-based method with guilt by association
      (GBA) principle (called as network-based gene function inference approach) based
      on gene oncology (GO) data and gene expression profile. To begin with,
      differentially expressed genes (DEGs) were extracted using linear models for
      microarray data (LIMMA) package. Then, construction of differential co-expression
      network (DCN) relying on DEGs was implemented, and sub-DCN was identified using
      Spearman correlation coefficient (SCC). Subsequently, GO annotations for OS were
      collected according to known confirmed database and DEGs. Ultimately, gene
      functions were predicted by means of GBA principle based on the area under the
      curve (AUC) for GO terms, and we determined GO terms with AUC >0.7 as the optimal
      gene functions for OS. Totally, 123 DEGs and 137 GO terms were obtained for
      further analysis. A DCN was constructed, which included 123 DEGs and 7503
      interactions. A total of 105 GO terms were identified when the threshold was set
      as AUC >0.5, which had a good classification performance. Among these 105 GO
      terms, 2 functions had the AUC >0.7 and were determined as the optimal gene
      functions including angiogenesis (AUC =0.767) and regulation of immune system
      process (AUC =0.710). These gene functions appear to have potential for early
      detection and clinical treatment of OS in the future.

PMID- 28443231
TI  - Clinical characteristics and risk factors analysis of lung metastasis of benign
      giant cell tumor of bone.
AB  - Pulmonary metastasis of benign giant cell tumor of bone is very rare, and its
      biological behavior is difficult to predict. In the present study, we analyzed
      the clinical characteristics of and related risk factors for pulmonary metastasis
      of this tumor. Forty-six patients with lung metastasis were analyzed. In total,
      60.9% of the primary tumors were located around the knee joint. The Campanacci
      stage of all tumors was stage 3. Surgery of the primary tumor included curettage
      in 37 patients, resection in 8, and amputation in 1. Local recurrence after the
      primary surgery occurred in 34 patients. The recurrence rate, Campanacci stage,
      and surgical method were significant risk factors for lung metastasis. The median
      postoperative metastasis time in the lower limbs, upper limbs, and axial skeleton
      was 20.1, 7.9, and 1.4 months, respectively (p=0.010). The median metastasis time
      in patients with and without recurrence was 13.7 and 43.2 months, respectively
      (p=0.018). Eighteen patients had unilateral metastasis and 28 had bilateral
      metastasis. Most lesions (n=38) were located in the peripheral lung. Nineteen
      patients received treatment, and 12 of them underwent tumor resection. The 5-year
      overall survival rate was 94.4%. This study showed that local recurrence, a high
      Campanacci stage, and curettage were possible high-risk factors for pulmonary
      metastasis. The primary lesion site and local recurrence may be related to the
      metastasis time. The survival rate of patients with pulmonary metastasis was
      high.

PMID- 28443232
TI  - A researcher's perspective on the quantity of osteosarcoma in vitro studies.
AB  - Osteosarcoma is a primary malignant bone tumour, for which no improvement in
      survival rate has been made since the nineteen seventies. We set out to
      systemically identify the in vitro studies performed in the past two decades
      describing potential future therapies. Strikingly, we obtained a total of 5282
      PubMed hits on this subject. The amount of publications has increased almost
      exponentially over the past few years. Studies from Chinese institutes are mainly
      responsible for this huge increase, accounting for 53% of the publications in
      2015. Approximately 1/3 of all drugs described in the past three years could be
      classified as traditional medicine. Furthermore, it struck our attention that
      even though in such studies multiple cell lines are essential to represent the
      heterogeneity in patients, many studies were performed with only one or two cell
      lines, i.e. U-2 OS or MG-63. These cells are fast growing, facilitating rapid
      experimental application but also boosting drug responsiveness. This probably
      explains why so many in vitro studies have been published for this relatively
      rare disease. Furthermore, it illustrates the current publication pressure,
      especially in China.

PMID- 28443233
TI  - A case of immunoglobulin G4-related respiratory disease with multiple lung cysts:
      A case report.
AB  - A 48-year-old man was admitted for evaluation of abnormal shadows on chest
      radiograph. Chest computed tomography (CT) showed cysts, nodules, and cervical
      and axillary lymphadenopathies. Elevated serum levels of IgG4 and interleukin
      (IL)-6 suggested IgG4-related disease (IgG4-RD) or multicentric Castleman's
      disease (MCD). Histologic findings of the cervical lymph node and right lung S6
      biopsies revealed numerous IgG4-positive plasma cells. Although CT findings of
      the lungs were atypical for IgG4-RD, consistent histologic findings, clinical
      symptoms, and laboratory data made us conclude IgG4-RD. Because histologic
      findings of IgG4-RD and MCD have similarities, differentiating between the two
      diseases should consider the clinical presentation.

PMID- 28443234
TI  - Plastic bronchitis: An unusual complication of acute chest syndrome in adult.
AB  - Plastic bronchitis is used to designate endobronchial plugs of rubber-like
      consistency that form into bronchial trees. It has been described in several
      diseases like asthma, cystic fibrosis, pulmonary infection, cyanotic congenital
      heart disease and in few young children with homozygous sickle cell disease. We
      report the first sickle cell adult case of plastic bronchitis during acute chest
      syndrome. He developed severe acute respiratory distress syndrome. This unusual
      presentation related to obstruction by voluminous casts may alert physicians to
      focus more on the bronchi in sickle cell patients. Realization of fiberoptic
      bronchoscopy to diagnose endobronchial injury and preventive measures such as
      fluidification of sputum at the early stage of thoracic vaso-occlusive crisis are
      essential.

PMID- 28443235
TI  - Seronegative, complicated hydatid cyst of the lung: A case report.
AB  - Cystic echinococcosis (CE) is an important helminthic zoonotic disease that
      commonly affects the liver and lungs. Imaging methods and serology establish the
      diagnosis in most cases. Chest x-ray can diagnose uncomplicated pulmonary hydatid
      cysts, whereas superinfection and/or rupture of the hydatid cyst (complicated
      cysts) may change the radiographic appearance and lead to delayed diagnosis and
      treatment. We report the case of a patient with hemoptysis and chest pain, where
      computer tomography scan of the lung suggested a large, ruptured hydatid cyst.
      However, serological tests with indirect hemagglutination (IHA)for Echinococcus
      granulosus antibodies were negative, and there was massive growth of
      Streptococcus pneumoniae in sputum. Based on this, we concluded that the patient
      had a bacterial lung abscess. The diagnosis of CE was only made after surgical
      removal of the cyst followed by microscopy and polymerase chain reaction.

PMID- 28443236
TI  - A case of intravascular large B-cell lymphoma of lung presenting with progressive
      multiple nodules on chest computed tomography.
AB  - A 71-year-old man was admitted to our hospital for dyspnea, which had worsened
      over a period of more than six months. He was previously diagnosed as having
      cryptogenic organizing pneumonia, and was treated with steroids in another
      hospital. He had complained of worsening dyspnea, despite the treatment. We
      performed video-assisted thoracoscopic surgery because of the high level of
      lactate dehydrogenase and inconsistency of the usual interstitial pneumonia
      pattern. Pathologic specimens showed atypical lymphocytes confined to the
      pulmonary capillaries. On immunohistochemical staining, tumor cells were found
      positive for CD20, without the T-cell marker. It was consistent with findings of
      intravascular large B-cell lymphoma. We report this case, which presented with
      progressive multiple nodules on chest computed tomography.

PMID- 28443237
TI  - The clinical heterogeneity of late-onset MELAS.

PMID- 28443238
TI  - A Case Report of Giant Adrenal Ganglioneuroma.
AB  - Adrenal ganglioneuroma (AGN) is an extremely rare and benign entity comprising
      Schwann cells and ganglion cells. If the lesion approaches to 6 cm, laparoscopic
      resection is considered as relative contraindication. Now we present a giant
      adrenal AGN in a 25-year-old male patient. After abdominal computed tomography
      (CT) scanning, the patient underwent an exploratory laparotomy with right
      adrenalectomy and histopathological examination further confirmed the lesions as
      giant AGN, which measured 7 cm * 5 cm * 3.5 cm. Because giant AGN with lesion
      size greater than 6 cm should be treated by open surgery, it is significant to
      report the laparoscopic adrenalectomy in patients with large adrenal lesions.

PMID- 28443239
TI  - Primitive Neuro Ectodermal Tumor Arising in a Testicular Teratoma with
      Retroperitoneal Metastasis: A Case Report and Review of Literature.
AB  - A 38-year-old man presenting with left testicular mass and extensive
      retroperitoneal lymphadenopathy underwent radical orchiectomy and specimen showed
      a germ cell tumor of primarily primitive neuroectodermal tumor mixed with mature
      teratoma. He then underwent RPLND, followed by adjuvant CAV (cyclophosphamide,
      doxorubicin, vincristine) and IE (ifosfamide, etoposide) alternating chemotherapy
      given the high rate of recurrence and high rate of response to the PNET-specific
      chemotherapy.

PMID- 28443240
TI  - Repair of Vesicocutaneous and Urethrocutaneous Fistulae with Rectus Muscle Flap
      in a Bladder Exstrophy Patient.
AB  - Urinary continence can be achieved in up to 90% of patients with bladder
      exstrophy. However, select patients remain incontinent despite modern
      reconstruction. Repeat operations for continence combined with the congenital
      pelvic abnormalities of exstrophy put patients at risk for urinary fistula
      formation. We report the use of a rectus muscle flap in the repair of two
      concomitant vesicocutaneous and urethrocutaneous fistulae in a patient with
      classic bladder exstrophy.

PMID- 28443241
TI  - Massive Renal Replacement Lipomatosis With Foci of Xanthogranulomatous
      Pyelonephritis in a Horseshoe Kidney.
AB  - Renal replacement lipomatosis (RRL) is a rare condition that occurs at the end of
      the spectrum of renal tissue replacement by fat. Xanthogranulomatous
      pyelonephritis (XGP) is a granulomatous inflammation characterized by destruction
      of renal parenchyma and replacement by lipid-laden macrophages. We present the
      case of a 75-year-old man who complained of severe anemia 34 years after right
      nephrolithotomy. Computed tomography revealed a huge low-density mass with renal
      parenchyma atrophy on the right side of horseshoe kidney. Right nephrectomy was
      performed. Pathological diagnosis was RRL with XGP. This is the first report of
      RRL with XGP in a horseshoe kidney.

PMID- 28443242
TI  - Incidental Leydig Cell Tumor in Patient with Hormone Resistant Prostate Cancer.
AB  - We hereby present the case of a 55 years old patient with clinical diagnosis of
      high-risk prostate cancer T2bN1Mo Gleason 9 (4 + 5) treated with androgen
      deprivation therapy and external beam radiotherapy. Despite treatment, castration
      levels were not achieved and clinical progression was evidenced by the appearance
      of bone metastases and progression of PSA. After several hormonal treatments
      without any PSA or testosterone response, surgical castration was performed by
      bilateral orchiectomy. The pathology results showed an incidental Leydig cell
      tumor in the right testicle.

PMID- 28443243
TI  - Association between Hashimoto's Thyroiditis and Thyroid Cancer in 64,628
      Patients.
AB  - BACKGROUND: The incidence of thyroid cancer (TC) is increasing although
      explanatory causes are lacking. A link between cancer and inflammation is well
      documented but unclear for autoimmune thyroid diseases and TC. We aimed to
      systematically review the association between Hashimoto's thyroiditis (HT) and
      papillary, follicular, medullary, anaplastic thyroid carcinoma, and thyroid
      lymphoma (TL). METHODS: PubMed, OVID Medline, Google Scholar, and the Cochrane
      Library were searched from 1955 to 2016. The inclusion criteria were age >18
      years, >=20 cases of HT or TC. We collectively examined the incidence of HT in TC
      and of TC in HT. RESULTS: We identified 36 studies (64,628 subjects) published
      between 1955 and 2016 from 13 countries. We found a relative risk (RR) of HT
      among papillary thyroid cancer (PTC) of 2.36 [95% confidence intervals (CIs) 1.55
      3.29, p < 0.001], an RR of PTC among HT of 1.40 (95% CI 1.07-1.85, p = 0.016),
      and an RR of TL among HT of 9.74 (95% CI 3.93-24.13, p < 0.001). CONCLUSION: We
      report an association between HT and PTC and between HT and TL. No association
      was found between HT and follicular, medullary, or anaplastic thyroid cancer.

PMID- 28443245
TI  - Overexpression of the ATPase Inhibitory Factor 1 Favors a Non-metastatic
      Phenotype in Breast Cancer.
AB  - Partial suppression of mitochondrial oxidative phosphorylation and the concurrent
      activation of aerobic glycolysis is a hallmark of proliferating cancer cells.
      Overexpression of the ATPase inhibitory factor 1 (IF1), an in vivo inhibitor of
      the mitochondrial ATP synthase, is observed in most prevalent human carcinomas
      favoring metabolic rewiring to an enhanced glycolysis and cancer progression.
      Consistently, a high expression of IF1 in hepatocarcinomas and in carcinomas of
      the lung, bladder, and stomach and in gliomas is a biomarker of bad patient
      prognosis. In contrast to these findings, we have previously reported that a high
      expression level of IF1 in breast carcinomas is indicative of less chance to
      develop metastatic disease. This finding is especially relevant in the bad
      prognosis group of patients bearing triple-negative breast carcinomas. To
      investigate the molecular mechanisms that underlie the differential behavior of
      IF1 in breast cancer progression, we have developed the triple-negative BT549
      breast cancer cell line that overexpresses IF1 stably. When compared to controls,
      IF1-cells partially shut down respiration and enhance aerobic glycolysis.
      Transcriptomic analysis suggested that migration and invasion were specifically
      inhibited in IF1-overexpressing breast cancer cells. Analysis of gene expression
      by qPCR and western blotting indicate that IF1 overexpression supports the
      maintenance of components of the extracellular matrix (ECM) and E-cadherin
      concurrently with the downregulation of components and signaling pathways
      involved in epithelial to mesenchymal transition. The overexpression of IF1 in
      breast cancer cells has no effect in the rates of cellular proliferation and in
      the cell death response to staurosporine and hydrogen peroxide. However, the
      overexpression of IF1 significantly diminishes the ability of the cells to grow
      in soft agar and to migrate and invade when compared to control cells. Overall,
      the results indicate that IF1 overexpression despite favoring a metabolic
      phenotype prone to cancer progression in the specific case of breast cancer cells
      also promotes the maintenance of the ECM impeding metastatic disease. These
      findings hence provide a mechanistic explanation to the better prognosis of
      breast cancer patients bearing tumors with high expression level of IF1.

PMID- 28443244
TI  - The Mitochondrial Voltage-Dependent Anion Channel 1, Ca2+ Transport, Apoptosis,
      and Their Regulation.
AB  - In the outer mitochondrial membrane, the voltage-dependent anion channel 1
      (VDAC1) functions in cellular Ca2+ homeostasis by mediating the transport of Ca2+
      in and out of mitochondria. VDAC1 is highly Ca2+-permeable and modulates Ca2+
      access to the mitochondrial intermembrane space. Intramitochondrial Ca2+ controls
      energy metabolism by enhancing the rate of NADH production via modulating
      critical enzymes in the tricarboxylic acid cycle and fatty acid oxidation.
      Mitochondrial [Ca2+] is regarded as an important determinant of cell sensitivity
      to apoptotic stimuli and was proposed to act as a "priming signal," sensitizing
      the organelle and promoting the release of pro-apoptotic proteins. However, the
      precise mechanism by which intracellular Ca2+ ([Ca2+]i) mediates apoptosis is not
      known. Here, we review the roles of VDAC1 in mitochondrial Ca2+ homeostasis and
      in apoptosis. Accumulated evidence shows that apoptosis-inducing agents act by
      increasing [Ca2+]i and that this, in turn, augments VDAC1 expression levels.
      Thus, a new concept of how increased [Ca2+]i activates apoptosis is postulated.
      Specifically, increased [Ca2+]i enhances VDAC1 expression levels, followed by
      VDAC1 oligomerization, cytochrome c release, and subsequently apoptosis. Evidence
      supporting this new model suggesting that upregulation of VDAC1 expression
      constitutes a major mechanism by which apoptotic stimuli induce apoptosis with
      VDAC1 oligomerization being a molecular focal point in apoptosis regulation is
      presented. A new proposed mechanism of pro-apoptotic drug action, namely Ca2+
      dependent enhancement of VDAC1 expression, provides a platform for developing a
      new class of anticancer drugs modulating VDAC1 levels via the promoter and for
      overcoming the resistance of cancer cells to chemotherapy.

PMID- 28443246
TI  - Genetic and Dietary Iron Overload Differentially Affect the Course of Salmonella
      Typhimurium Infection.
AB  - Genetic and dietary forms of iron overload have distinctive clinical and
      pathophysiological features. HFE-associated hereditary hemochromatosis is
      characterized by overwhelming intestinal iron absorption, parenchymal iron
      deposition, and macrophage iron depletion. In contrast, excessive dietary iron
      intake results in iron deposition in macrophages. However, the functional
      consequences of genetic and dietary iron overload for the control of microbes are
      incompletely understood. Using Hfe+/+ and Hfe-/- mice in combination with oral
      iron overload in a model of Salmonella enterica serovar Typhimurium infection, we
      found animals of either genotype to induce hepcidin antimicrobial peptide
      expression and hypoferremia following systemic infection in an Hfe-independent
      manner. As predicted, Hfe-/- mice, a model of hereditary hemochromatosis,
      displayed reduced spleen iron content, which translated into improved control of
      Salmonella replication. Salmonella adapted to the iron-poor microenvironment in
      the spleens of Hfe-/- mice by inducing the expression of its siderophore iron
      uptake machinery. Dietary iron loading resulted in higher bacterial numbers in
      both WT and Hfe-/- mice, although Hfe deficiency still resulted in better
      pathogen control and improved survival. This suggests that Hfe deficiency may
      exert protective effects in addition to the control of iron availability for
      intracellular bacteria. Our data show that a dynamic adaptation of iron
      metabolism in both immune cells and microbes shapes the host-pathogen interaction
      in the setting of systemic Salmonella infection. Moreover, Hfe-associated iron
      overload and dietary iron excess result in different outcomes in infection,
      indicating that tissue and cellular iron distribution determines the
      susceptibility to infection with specific pathogens.

PMID- 28443247
TI  - Evaluation of a New IFN-gamma Release Assay for Rapid Diagnosis of Active
      Tuberculosis in a High-Incidence Setting.
AB  - Blood-based interferon-gamma (IFN-gamma) release assays (IGRAs) have been proven
      to be useful in the diagnosis of Mycobacterium tuberculosis (Mtb) infection.
      However, IGRAs have not been recommended for clinical practice in most low-income
      settings due to cost-intensive limitations and shortage of clinical data
      available. The established T-SPOT. TB assay containing Mtb-specific antigens ESAT
      6 and CFP10 are widely used for immunodiagonsis of Mtb infection, but the high
      cost is one of the restricting factors against its clinical application in the
      developing countries. More recently, a cost-saving IGRA assay, TS-SPOT, was
      approved in China. This new assay contains an additional antigen Rv3615c. Rv3615c
      contains broadly recognized CD4+ and CD8+ epitopes, and T-cell responses to
      Rv3615c are as specific for Mtb infection as the responses to ESAT-6 and CFP10 in
      both Mtb-infected humans and M. bovis-infected cattle. Therefore, we assessed the
      likely effect of inclusion of Rv3615c as stimulus besides ESAT-6 and CFP10 in an
      IGRA assay and evaluated the performance of TS-SPOT for diagnosis of Mtb
      infection and active TB compared with T-SPOT.TB. We tested 155 active TB
      patients, 90 non-TB lung disease patients, and 55 healthy individuals. The
      results presented an improved positive rate for diagnosis of active TB and Mtb
      infection, that could be attributable to inclusion of Rv3615c in the mixture of
      stimulatory antigens. The diagnostic efficiency of TS-SPOT assay for active TB
      was as follows: sensitivity 80.00%, specificity 83.45%, positive predictive value
      (PPV) 83.78%, negative predictive value (NPV) 83.45%, positive likelihood ratio
      (LR+) 4.83, and negative likelihood ratio (LR-) 0.24. The results were similar to
      those of T-SPOT.TB, with an excellent agreement (kappa = 0.91, 95% CI: 0.85-0.95)
      being observed between these two assays. The sensitivities of the TS-SPOT assay
      varied for patients with different forms of active TB, with the highest
      sensitivity for patients with culture-positive pulmonary TB (92.16%) and the
      lowest for those with tuberculosis meningitis (50.00%). Taken together, the
      current evidence indicates that this new TS-SPOT assay is a useful adjunct to the
      current tests for rapid diagnosis of active TB and Mtb infection in low-income
      and high-incidence settings due to its characteristics of cost-effectiveness and
      high-quality.

PMID- 28443248
TI  - Shiga Toxin Subtypes of Non-O157 Escherichia coli Serogroups Isolated from Cattle
      Feces.
AB  - Shiga toxin producing Escherichia coli (STEC) are important foodborne pathogens
      responsible for human illnesses. Cattle are a major reservoir that harbor the
      organism in the hindgut and shed in the feces. Shiga toxins (Stx) are the primary
      virulence factors associated with STEC illnesses. The two antigenically distinct
      Stx types, Stx1 and Stx2, encoded by stx1 and stx2 genes, share approximately 56%
      amino acid sequence identity. Genetic variants exist within Stx1 and Stx2 based
      on differences in amino acid composition and in cytotoxicity. The objective of
      our study was to identify the stx subtypes in strains of STEC serogroups, other
      than O157, isolated from cattle feces. Shiga toxin gene carrying E. coli strains
      (n = 192), spanning 27 serogroups originating from cattle (n = 170) and human (n
      = 22) sources, were utilized in the study. Shiga toxin genes were amplified by
      PCR, sequenced, and nucleotide sequences were translated into amino acid
      sequences using CLC main workbench software. Shiga toxin subtypes were identified
      based on the amino acid motifs that define each subtype. Shiga toxin genotypes
      were also identified at the nucleotide level by in silico restriction fragment
      length polymorphism (RFLP). Of the total 192 STEC strains, 93 (48.4%) were
      positive for stx1 only, 43 (22.4%) for stx2 only, and 56 (29.2%) for both stx1
      and stx2. Among the 149 strains positive for stx1, 132 (88.6%) were stx1a and 17
      (11.4%) were stx1c. Shiga toxin 1a was the most common subtype of stx1 among
      cattle (87.9%; 123/140) and human strains (100%; 9/9) of non-O157 serogroups. Of
      the total 99 strains positive for stx2, 79 were stx2a (79.8%), 11 (11.1%) were
      stx2c, 12 (12.1%) were stx2d. Of the 170 strains originating from cattle feces,
      58 (34.1%) were stx2a subtype, 11 (6.5%) were stx2c subtype, and 11 were of
      subtype stx2d (6.5%). All but one of the human strains were positive for stx2a.
      Three strains of cattle origin were positive for both stx2a and stx2d. In
      conclusion, a number of non-O157 STEC serogroups harbored by cattle possess a
      wide variety of Shiga toxin subtypes, with stx1a and stx2a being the most
      predominant stx subtypes occurring individually or in combination. Cattle are a
      reservoir of a number of non-O157 STEC serogroups and information on the Shiga
      toxin subtypes is useful in assessing the potential risk as human pathogens.

PMID- 28443250
TI  - Pectoralis Major Tear: An Unusual and Rare Presentation.
AB  - INTRODUCTION: The pectoralis major is a very powerful muscle that forms the chest
      prominence and. It moves the shoulder forward and across your chest. It is best
      known as the muscle that you develop with the bench press exercise in gymnasium.
      The pectoralis major attaches to the humerus bone and is divided into two parts.
      The upper part is known as the "clavicular head" and the lower part the "sternal
      head," based on their origins from the clavicle and sternal bones, respectively.
      Ruptures of the pectoralis major muscle are becoming more common due to the
      increase in power sports weight training. CASE REPORT: A About 25-year-old male
      presented to Out Patient Department with bruising and swelling over the anterior
      wall of left axilla. The patient was engineer and amateur weight lifter.
      Clinically, the swelling was tender, and movements of left arm were restricted.
      Muscle tear was suspected and hence magnetic resonance imaging (MRI) was advised
      which showed tear of tendon of pectoralis major muscle. The patient was treated
      surgically and has got full range of movements of the arm. CONCLUSION: MRI is the
      mainstay for diagnosing pectoralis major tear. The earlier a repair is performed
      the easier the surgery and the better the outcome of surgery.

PMID- 28443251
TI  - Partial Heel Pad Avulsion with Open Calcaneal Tuberosity Fracture with Tendo
      achilles Rupture: A Case Report.
AB  - INTRODUCTION: The management of heel pad avulsion injuries has been challenging
      because of the precarious blood supply. The difficulties get compounded when it
      is associated with tendo-achilles rupture and calcaneal fracture. Here, it is a
      description of a case with the above features managed with a unique technique.
      CASE REPORT: A 63-year-old woman presented to casualty with injury to right ankle
      after a road traffic accident. On clinical and radiological examination, there
      was avulsion of heel pad with calcaneal tuberosity fracture and tendo-achilles
      rupture. It was managed with debridement of the wound, repair of tendo-achilles,
      and fixation of calcaneal tuberosity and heel pad. The functional outcome was
      assessed in terms of the ability of the patient to return to painless barefoot
      weight bearing. The uniqueness of this method is the combined use of suture
      material (Ethibond) and stainless steel (cannulated cancellous screws [CCS]), by
      tying the Ethibond from tendo-achilles to the head of CCS rather than bone. When
      the CCS were tightened, two things were achieved; one being the reduction of the
      fracture and the second to bring a good apposition of tendo-achilles with the
      calcaneum. As this method worked on tension band principle and Ethibond was used
      instead of stainless steel wire, if no objections, this technique can be called
      as "soft tension band technique." CONCLUSION: This case report illustrates a
      method of preserving heel pad when it is viable along with definitive treatment
      of associated soft tissue and bony injuries by a simple technique. This method
      has described the fixation of open fracture of calcaneal tuberosity with tendo
      achilles rupture with heel pad avulsion in one sitting with excellent clinical
      results.

PMID- 28443249
TI  - Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of
      the Data Obtained In vitro and in Animal Models.
AB  - The antibiotic classes that are recommended for tularaemia treatment are the
      aminoglycosides, the fluoroquinolones and the tetracyclines. However, cure rates
      vary between 60 and 100% depending on the antibiotic used, the time to
      appropriate antibiotic therapy setup and its duration, and the presence of
      complications, such as lymph node suppuration. Thus, antibiotic susceptibility
      testing (AST) of F. tularensis strains remains of primary importance for
      detection of the emergence of antibiotic resistances to first-line drugs, and to
      test new therapeutic alternatives. However, the AST methods reported in the
      literature were poorly standardized between studies and AST data have not been
      previously evaluated in a comprehensive and comparative way. The aim of the
      present review was to summarize experimental data on antibiotic susceptibilities
      of F. tularensis obtained in acellular media, cell models and animal models since
      the introduction of fluoroquinolones in the treatment of tularaemia in 1989. We
      compiled MIC data of 33 antibiotics (including aminoglycosides, fluoroquinolones,
      tetracyclines, macrolides, beta-lactams, chloramphenicol, rifampicin, and
      linezolid) against 900 F. tularensis strains (504 human strains), including 107
      subsp. tularensis (type A), 789 subsp. holarctica (type B) and four subsp.
      mediasiatica strains, using various AST methods. Specific culture media were
      identified or confirmed as unsuitable for AST of F. tularensis. Overall, MICs
      were the lowest for ciprofloxacin (<= 0.002-0.125 mg/L) and levofloxacin, and
      ranged from <= 0.016 to 2 mg/L for gentamicin, and 0.064 to 4 mg/L for
      doxycycline. No resistant strain to any of these antibiotics was reported.
      Fluoroquinolones also exhibited a bactericidal activity against intracellular F.
      tularensis and lower relapse rates in animal models when compared with the
      bacteriostatic compound doxycycline. As expected, lower MIC values were found for
      macrolides against type A and biovar I type B strains, compared to biovar II type
      B strains. The macrolides were more effective against F. tularensis grown in
      phagocytic cells than in acellular media.

PMID- 28443253
TI  - Bone modeling, remodeling, and skeletal health in children and adolescents:
      mineral accrual, assessment and treatment.
AB  - The modeling and remodeling process of the bone is fundamental to maintaining its
      integrity and mechanical properties. Many physical and biochemical factors during
      childhood and adolescence are crucially important for the development of healthy
      bones. Systemic conditions, such as hormonal status, nutrition, physical
      inactivity, or many pharmacological treatments, as well as a local variation in
      the load, can influence bone turnover and, consequently, the attainment of a
      proper peak bone mass. However, many diseases affecting children and adolescents
      can be associated with a reduction in bone accrual or a loss of bone mass and
      quality, which leads to an increased risk of fracture over one's life. In this
      review, we examine the effects of genetics, physical activity, chronic diseases
      and pharmacological treatments, and dietary factors on bone integrity in children
      and adolescents. We also briefly describe the specific tools that are currently
      used in assessing bone health.

PMID- 28443252
TI  - Open-label Phase II clinical trial in 75 patients with advanced hepatocellular
      carcinoma receiving daily dose of tableted liver cancer vaccine,
      hepcortespenlisimut-L.
AB  - BACKGROUND: An increasing number of studies is now devoted to immunotherapy of
      cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5
      [formerly known as V5])-an oral therapeutic vaccine designated by the United
      States Food and Drug Administration (FDA) as an orphan drug for treatment of
      hepatocellular carcinoma (HCC). V5 was initially developed by us in 2002 to treat
      hepatitis B or C viral infections and liver cirrhosis. METHODS: The outcome of
      open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively.
      Over a period of 5 years, 75 patients with advanced HCC were enrolled, consisting
      of 29 (38.7%) females and 46 (61.3%) males with a median age of 60 years (mean
      61.6+/-8.1 years). Out of these, 23 (30.7%) had hepatitis B and 34 (45.3%) had
      hepatitis C infections, including 9 (12%) with dual infection, 4 (5.3%) negative
      for both viruses, and 5 (6.7%) without established viral diagnosis. Most patients
      (94.7%) had underlying liver cirrhosis of varying severity. RESULTS: After a
      median of 2 months of treatment, 50 out of 75 patients had experienced a decline
      in serum levels of the tumor marker, alpha-fetoprotein (AFP) (66.7%; P=0.006 by
      Wilcoxon signed rank test). Baseline median AFP levels were 245.2 IU/mL (mean
      4,233; range 7.2-92,407; 95% confidence interval [CI] 1,186-7,280) and post
      treatment values were 102.3 IU/mL (mean 2,539; range 0.9-54,478; 95% CI 503
      4,575). The decrease in AFP was correlated either with tumor clearance or
      regression on computed tomography scans. The median overall survival time could
      not be established since 68 out of 75 (90.7%) patients were still alive after
      median follow-up of 12 months (mean 15+/-9.7; range 7-59; 95% CI 12.8-17.2). The
      first patient in this study received immunotherapy 5 years ago and still remains
      in complete remission. None of the patients experienced any serious adverse
      effects or toxicity. CONCLUSION: The results indicate that hepcortespenlismut-L
      is a safe, effective, and fast-acting immunomodulatory intervention for HCC. The
      Phase III, randomized, double-blind, placebo-controlled trial is now initiated at
      the Mongolian National Cancer Center to confirm these promising findings.

PMID- 28443254
TI  - Perfluoroalkyl substances exposure and thyroid hormones in humans:
      epidemiological observations and implications.
AB  - Thyroid hormones play crucial roles in normal neurodevelopment of fetus and
      child. Many chemicals can affect control and homeostasis of thyroid hormones, and
      eventually lead to various adverse health effects including neurodevelopmental
      disorders. Perfluoroalkyl substances (PFASs) are among the thyroid disrupting
      chemicals that can be encountered among general human population. Due to their
      unique physicochemical characteristics, PFASs have been used as surfactants and
      surface coating materials in many applications. Therefore, PFASs have been
      frequently detected in humans and environment worldwide. In cross-sectional
      studies using nationally representative general human populations of United
      States, several PFASs have shown significant associations with thyroid hormones.
      Moreover, among pregnant women and their infants, not only major PFASs such as
      perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with
      shorter or longer carbon chains showed significant associations with thyroid
      hormones. Often demographic characteristics such as sex, age, and disease status
      appear to influence the associations between PFASs exposure and thyroid hormones.
      In general, major PFASs showed hypothyroidism effects among pregnant women and
      infants. As 8 carbon based PFASs have been phased out, those with shorter or
      longer carbon chains have been used in growing amount as replacement. However,
      only limited information is available for their occurrences and toxicity among
      humans. Further investigations on these substituting PFASs are required. In
      addition, efforts are warranted to identify sources of and mitigate exposure to
      these thyroid disrupting chemicals especially during pregnancy and early stages
      of life.

PMID- 28443255
TI  - Glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists in the
      treatment of type 2 diabetes.
AB  - The prevalence of type 2 diabetes (T2D) is increasing worldwide. Patients with
      T2D suffer from various diabetes-related complications. Since there are many
      patients with T2D that cannot be controlled by previously developed drugs, it has
      been necessary to develop new drugs, one of which is a glucagon-like peptide-1
      (GLP-1) based therapy. GLP-1 has been shown to ameliorate diabetes-related
      conditions by augmenting pancreatic beta-cell insulin secretion and having the
      low risk of causing hypoglycemia. Because of a very short half-life of GLP-1,
      many researches have been focused on the development of GLP-1 receptor (GLP-1R)
      agonists with long half-lives such as exenatide and dulaglutide. Now GLP-1R
      agonists have a variety of dosing-cycle forms to meet the needs of various
      patients. In this article, we review the physiological features of GLP-1, the
      effects of GLP-1 on T2D, the features of several GLP-1R agonists, and the
      therapeutic effect on T2D.

PMID- 28443256
TI  - Change in body mass index and insulin resistance after 1-year treatment with
      gonadotropin-releasing hormone agonists in girls with central precocious puberty.
AB  - PURPOSE: Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic
      agent for central precocious puberty (CPP); however, increased obesity may
      subsequently occur. This study compared body mass index (BMI) and insulin
      resistance during the first year of GnRHa treatment for CPP. METHODS: Patient
      group included 83 girls (aged 7.0-8.9 years) with developed breasts and a peak
      luteinizing hormone level of >=5 IU/L after GnRH stimulation. Control group
      included 48 prepubertal girls. BMI and insulin resistance-related indices
      (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative
      insulin sensitivity check index [QUICKI]) were used to compare the groups before
      treatment, and among the patient group before and after GnRHa treatment. RESULTS:
      No statistical difference in BMI z-score was detected between the 2 groups before
      treatment. Fasting insulin and HOMA-IR were increased in the patient group;
      fasting glucose-to-insulin ratio and QUICKI were increased in the control group
      (all P<0.001). In normal-weight subjects in the patient group, BMI z-score was
      significantly increased during GnRHa treatment (-0.1+/-0.7 vs. 0.1+/-0.8,
      P<0.001), whereas HOMA-IR and QUICKI exhibited no differences. In overweight
      subjects in the patient group; BMI z-score and HOMA-IR were not significantly
      different, whereas QUICKI was significantly decreased during GnRHa treatment
      (0.35+/-0.03 vs. 0.33+/-0.02, P=0.044). CONCLUSION: Girls with CPP exhibited
      increased insulin resistance compared to the control group. During GnRHa
      treatment, normal-weight individuals showed increased BMI z-scores without
      increased insulin resistance; the overweight group demonstrated increased insulin
      resistance without significantly altered BMI z-scores. Long-term follow-up of BMI
      and insulin resistance changes in patients with CPP is required.

PMID- 28443257
TI  - Influence of The -202 A/C insulin-like growth factor-binding protein-3 promoter
      polymorphism on individual variation in height in Korean girls.
AB  - PURPOSE: The most common single nucleotide polymorphism in the IGFBP3 promoter
      region occurs at position -202. This polymorphic variation occurs frequently and
      may influence growth hormone responsiveness and somatic growth. However, the
      effects of IGFBP3 promoter polymorphism on growth in children are unknown.
      METHODS: Restriction fragment length polymorphism-based genotyping of the -202
      single nucleotide polymorphism was performed in 146 Korean girls aged between 15
      and 16 years, who were selected randomly from the Seoul School Health Promotion
      Center. The participants were divided into 3 groups (tall, medium, and short)
      according to the height percentile established from normal reference values for
      Korean children. The serum levels of insulin-like growth factor I (IGF-I) and IGF
      binding protein-3 (IGFBP-3) were then compared according to genotype. RESULTS:
      The genotype distribution in the participants was 79 AA (54.1%), 60 AC (41.1%),
      and 7 CC (4.8%). The C allele frequency at the -202 IGFBP3 position was 25.4% in
      this group. The mean serum IGFBP-3 concentration in girls with the AA genotype
      was higher than that in girls with the AC genotype in the medium (P=0.047) and
      short (P=0.035) groups, respectively. There was no difference in the IGF-I to
      IGFBP-3 molar ratio between the AA and AC genotype groups (P=0.161). CONCLUSION:
      In conclusion, the -202 polymorphism in the IGFBP3 promoter region is assumed to
      affect the serum concentration of IGFBP-3 in children as well as in adults.
      However, it is unclear whether this affects physical development according to the
      concentration of IGFBP-3.

PMID- 28443258
TI  - The effect of first nocturnal ejaculation timing on risk and sexual behaviors of
      Korean male adolescents.
AB  - PURPOSE: This study evaluated the effect of first nocturnal ejaculation timing on
      risk and sexual behaviors of Korean male adolescents. METHODS: We analyzed data
      from the 10th edition of the Korea Youth Risk Behavior Web-based survey that was
      conducted with male high school adolescents in grades 10-12. The survey included
      17,907 adolescents, and 10,326 responded their experience of first nocturnal
      ejaculation. Of these, 595 had their first nocturnal ejaculation in <=grade 4
      ("early puberty") and 9,731 had their first nocturnal ejaculation in >=grade 5
      ("normal puberty"). We analyzed differences between these 2 groups in risk and
      sexual behaviors. RESULTS: Early first nocturnal ejaculation showed a positive
      association with sexual intercourse (odds ratio [OR], 3.27; 95% confidence
      interval [CI], 2.56-4.17), sexual debut at elementary school age (OR, 7.45; 95%
      CI, 5.00-11.10), and having had a sexually transmitted disease (OR, 6.60; 95% CI,
      3.94-11.08). After a multiple logistic regression to adjust for socio-demographic
      variables, early first nocturnal ejaculation was still positively associated with
      sexual intercourse (OR, 2.73; 95% CI, 2.03-3.69), sexual debut at elementary
      school age (OR, 5.96; 95% CI, 3.47-10.22), and having had a sexually transmitted
      disease (OR, 5.17; 95% CI, 2.52-10.20). Early first nocturnal ejaculation was
      positively associated with alcohol consumption, smoking, and substance use.
      However, this was not statistically significant after adjusting for several socio
      demographic variables. CONCLUSION: There is a positive association between early
      nocturnal ejaculation and sexual behaviors in male adolescents. Proactive
      education about sexual behaviors is required for adolescents who reach sexual
      maturity early.

PMID- 28443259
TI  - The different effects of gonadotropin-releasing hormone agonist therapy on body
      mass index and growth between normal-weight and overweight girls with central
      precocious puberty.
AB  - PURPOSE: The effects of gonadotropin-releasing hormone agonist (GnRHa) treatment
      on body mass index (BMI) are controversial in girls with central precocious
      puberty (CPP). We therefore evaluated auxological parameters during GnRHa therapy
      in patients with CPP, specifically focusing on changes in BMI. METHODS: Seventy
      seven girls with idiopathic CPP who underwent GnRHa therapy were retrospectively
      recruited. We investigated BMI changes during the treatment period after
      stratifying them according to baseline BMI status as follows: normal (BMI
      percentile of <85th) and overweight groups (BMI percentile of >=85th). RESULTS:
      The incidence of overweight/obesity (40.3%/23.4%) was very high in the girls with
      CPP. In the overall study population, no significant BMI change was observed
      during the GnRHa treatment period. However, when stratified according to baseline
      BMI status, the normal-weight group showed a significant increase in BMI-standard
      deviation score (SDS), whereas the overweight group showed no change in BMI-SDS.
      Baseline BMI-SDS was an independent predictor of changes in BMI during the GnRHa
      treatment period. Changes in weight-SDS were similar, but changes in height-SDS
      were significantly greater in the overweight group than in the normal-weight
      group, which explains the observed difference in BMI-SDS. CONCLUSION: Our results
      demonstrate that the difference in the pattern of BMI changes among our CPP
      patients suggests that delayed puberty induced by GnRHa treatment may have
      different effects on linear growth according to baseline body composition. This
      study underscores the importance of individualized lifestyle intervention in CPP
      children.

PMID- 28443260
TI  - Growth without growth hormone in combined pituitary hormone deficiency caused by
      pituitary stalk interruption syndrome.
AB  - Growth hormone (GH) is an essential element for normal growth. However, reports
      of normal growth without GH have been made in patients who have undergone brain
      surgery for craniopharyngioma. Normal growth without GH can be explained by
      hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants;
      however, its exact mechanism has not been elucidated yet. We diagnosed a female
      patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by
      pituitary stalk interruption syndrome (PSIS). The patient has experienced
      recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at
      the age of 13, showing normal growth. She grew another 8 cm for 3 years after the
      diagnosis, and she reached her final adult height of 168 cm which was greater
      than the midparental height, at the age of 16. The patient's blood GH and insulin
      like growth factor-I levels were consistently subnormal, although her insulin
      levels were normal. Her physical examination conducted at the age of 15 showed
      truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of
      GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD
      patient attained her final height above mid parental height despite a severe GHD.

PMID- 28443261
TI  - Diabetes mellitus caused by secondary hemochromatosis after multiple blood
      transfusions in 2 patients with severe aplastic anemia.
AB  - Hemochromatosis is an inherited or secondary disorder caused by excessive iron
      storage leading to multiple organ damage. We describe 2 patients with diabetes
      mellitus caused by hemochromatosis secondary to multiple blood transfusions due
      to severe aplastic anemia. Subject 1, who was diagnosed with severe aplastic
      anemia at 15 years of age, received multiple red blood cell transfusions before
      he underwent autologous peripheral blood stem cell transplantation (PBSCT) at 22
      years of age. At 21 years of age, hyperglycemia was detected with increased
      hemoglobin A1c and serum ferritin levels, 9.7% and 12,910 ng/mL (normal range, 20
      320 ng/mL), respectively. The 24-hour urine C-peptide level was normal with
      negative antiglutamic acid decarboxylase antibody. Subsequently, metformin and an
      iron-chelating agent were administered. However, an intensive insulin regimen was
      necessary 2 years after the onset of diabetes. Subject 2, who was diagnosed with
      severe aplastic anemia at 2 years of age, received multiple blood transfusions
      until she underwent haploidentical PBSCT at 13 years of age. At 11 years of age,
      she developed diabetes mellitus with a high serum ferritin level (12,559.8
      ng/mL). She is currently 18 years old and has been treated with an intensive
      insulin regimen and estrogen/progesterone replacement therapy because of
      hypogonadotropic hypogonadism. It is presumed that the loss of insulin secretory
      capacity and insulin resistance played a role in the pathogenesis of diabetes
      mellitus due to hemochromatosis in these cases.

PMID- 28443262
TI  - A rare association of central hypothyroidism and adrenal insufficiency in a boy
      with Williams-Beuren syndrome.
AB  - Primary hypothyroidism related to morphological and volumetric abnormalities of
      the thyroid gland is one of the commonest of several endocrine dysfunctions in
      Williams-Beuren syndrome (WBS). We report a 10-month-old boy with WBS who
      presented with central hypothyroidism. During the neonatal period, he had
      prolonged jaundice, feeding difficulties and episodes of colic that continued
      during early infancy. Additionally, there was slowing of growth and mild
      developmental delay. He underwent surgical repair for supravalvular aortic
      stenosis at 6 months of age. An evaluation done to exclude cortisol deficiency
      before initiating levothyroxine lead to the detection of secondary adrenal
      insufficiency, unreported previously in WBS. In addition, insulin-like growth
      factor-1 (IGF-1) and IGF-binding protein-3 levels were low. This report of
      hypopituitarism in WBS indicates a need for complete evaluation of pituitary
      dysfunction in children with WBS.

PMID- 28443263
TI  - A 1-month-old infant with chylomicronemia due to GPIHBP1 gene mutation treated by
      plasmapheresis.
AB  - Chylomicronemia is a severe type of hypertriglyceridemia characterized by
      chylomicron accumulation that arises from a genetic defect in intravascular
      lipolysis. It requires urgent and proper management, because serious cases can be
      accompanied by pancreatic necrosis or persistent multiple organ failure. We
      present the case of a 1-month-old infant with chylomicronemia treated by
      plasmapheresis. His chylomicronemia was discovered incidentally when lactescent
      plasma was noticed during routine blood sampling during a hospital admission for
      fever and irritability. Laboratory investigation revealed marked triglyceridemia
      (>5,000 mg/dL) with high chylomicron levels. We therefore decided to perform a
      therapeutic plasmapheresis to prevent acute pancreatitis. Sequence analysis
      revealed a homozygous novel mutation in exon 4 of GPIHBP1: c.476delG
      (p.Gly159Alafs). Glycosylphosphatidylinositol-anchored high density lipoprotein
      binding protein 1 (GPIHBP1) stabilizes the binding of chylomicrons near
      lipoprotein lipase and supports lipolysis. Mutations of GPIHBP1, the most
      recently discovered gene, can lead to severe hyperlipidemia and are known to make
      up only 2% of the monogenic mutations associated with chylomicronemia. The
      patient maintains mild hypertriglyceridemia without rebound after single
      plasmapheresis and maintenance fibrate medication so far. Here, we report an
      infant with chylomicronemia due to GPIHBP1 mutation, successfully treated by
      plasmapheresis.

PMID- 28443264
TI  - Cancer incidence attributable to alcohol consumption in Alberta in 2012.
AB  - BACKGROUND: Alcohol consumption has been associated with risk of oral
      cavity/pharyngeal, laryngeal, esophageal, liver, colorectal and breast cancers.
      The purpose of this study was to estimate the proportion and total number of
      these cancers in Alberta in 2012 attributable to alcohol consumption. METHODS: We
      estimated cancers attributable to alcohol consumption in adults in Alberta using
      population attributable risk calculations. Relative risks were obtained from
      recent meta-analyses, and alcohol consumption in Alberta was quantified with the
      use of data from the Canadian Community Health Survey. We obtained age-, site-
      and sex-specific cancer incidence data for 2012 from the Alberta Cancer Registry.
      The impact of potential underestimation of alcohol consumption in Canadian
      Community Health Survey data was evaluated with the use of per-capita alcohol
      sales data from Statistics Canada. RESULTS: Proportions of cancers attributable
      to alcohol consumption at individual cancer sites were estimated to be as low as
      5.1% (liver) and as high as 19.9% (oral cavity/pharynx) among men and as low as
      2.1% (liver) and as high as 7.6% (oral cavity/pharynx) among women in Alberta.
      The total number of alcohol-attributable cancer cases was highest for common
      cancers (colorectal, female breast), whereas at individual cancer sites,
      population attributable risks were highest for upper aerodigestive tract cancers.
      A total of 4.8% of alcohol-associated cancers (1.6% of all cancers) in Alberta
      could be attributed to alcohol consumption. After adjustment for recorded alcohol
      consumption, our estimates of population attributable risk increased to 10.7% of
      alcohol-associated cancers and 3.5% of all cancers. INTERPRETATION: Alcohol
      consumption is estimated to account for 1.6%-3.5% of total cancer cases in
      Alberta. Given that no level of alcohol consumption is considered safe with
      respect to cancer risk, strategies to reduce alcohol consumption have the
      potential to reduce Alberta's cancer burden.

PMID- 28443265
TI  - Registration for deceased organ and tissue donation among Ontario immigrants: a
      population-based cross-sectional study.
AB  - BACKGROUND: Canada has low rates of deceased organ and tissue donation.
      Immigrants to Canada may differ in their registered support for deceased organ
      donation based on their country of origin. METHODS: We used linked administrative
      databases in Ontario (about 11 million residents aged >= 16 yr) to study the
      proportion of immigrants and long-term residents registered for deceased organ
      and tissue donation as of October 2013. We used modified Poisson regression to
      identify and quantify predictors of donor registration. RESULTS: Compared with
      long-term residents (n = 9 244 570), immigrants (n = 1 947 646) were much less
      likely to register for deceased organ and tissue donation (11.9% v. 26.5%).
      Immigrants from the United States, Australia and New Zealand had the highest
      registration rate (40.0%), whereas immigrants with the lowest registration rates
      were from Eastern Europe and Central Asia (9.4%), East Asia and Pacific (8.4%)
      and sub-Saharan Africa (7.9%). The largest numbers of unregistered immigrants
      were from India (n = 202 548), China (n = 186 678) and the Philippines (n = 125
      686). Characteristics among the immigrant population associated with a higher
      likelihood of registration included economic immigrant status, living in a rural
      area (population < 10 000), living in an area with a lower ethnic concentration,
      less material deprivation, a higher education, ability to speak English and
      French, and more years residing in Canada. INTERPRETATION: Immigrants in Ontario
      were less likely to register for deceased organ and tissue donation than long
      term residents. There is a need to better understand reasons for lower
      registration rates among Canadian immigrants and to create culture-sensitive
      materials to build support for deceased organ and tissue donation.

PMID- 28443266
TI  - Cost-effectiveness of palivizumab compared to no prophylaxis in term infants
      residing in the Canadian Arctic.
AB  - BACKGROUND: Hospital admissions for respiratory syncytial virus infection result
      in large health expenditures for Inuit infants. Palivizumab has been shown to be
      highly effective in reducing such admissions in preterm Inuit infants. We
      performed a cost-effectiveness analysis estimating the incremental cost
      effectiveness ratio (ICER) for palivizumab prophylaxis per admission related to
      respiratory syncytial virus avoided in healthy term infants across the Canadian
      Arctic. METHODS: We compared universal palivizumab prophylaxis in term infants
      less than 6 months of age to no prophylaxis in 8 Arctic regions: the Northwest
      Territories, Nunavut, Nunavut without Iqaluit, the 3 subregions of Nunavut
      (Kitikmeot, Kivalliq and Qikiqtaaluk), the Qikiqtaaluk Region without Iqaluit,
      and Nunavik (northern Quebec). Costs were acquired from the territorial
      governments, hospitals and contracted agencies. The perspective is that of the
      public payer, with a 6-month timeline. In scenario A, universal prophylaxis was
      provided until the end of the respiratory syncytial virus season, and in scenario
      B, infants received prophylaxis until 5 months of age. The ICERs of scenario A
      were compared with those of scenario B. RESULTS: Under scenario A, the cost per
      admission avoided was as high as $546 115 in the Northwest Territories, compared
      with a cost savings of $36 145 in the Kitikmeot Region. Under scenario B, the
      ICER showed cost savings of $48 549 in the Kitikmeot Region and $2731 in the
      Kivalliq Region, with low ICERs in Nunavik of $15 601. INTERPRETATION:
      Considerable cost savings were found for the Kitikmeot Region with universal
      palivizumab prophylaxis in term infants with both scenarios, whereas cost savings
      were found for the Kivalliq Region with scenario B. Stopping prophylaxis at 5
      months of age was a more cost-effective strategy in all regions except the
      Kitikmeot Region. Nunavik had low ICERs, and prophylaxis should be considered for
      this region.

PMID- 28443267
TI  - No Impact of the Analytical Method Used for Determining Cystatin C on Estimating
      Glomerular Filtration Rate in Children.
AB  - BACKGROUND: Measurement of inulin clearance is considered to be the gold standard
      for determining kidney function in children, but this method is time consuming
      and expensive. The glomerular filtration rate (GFR) is on the other hand easier
      to calculate by using various creatinine- and/or cystatin C (Cys C)-based
      formulas. However, for the determination of serum creatinine (Scr) and Cys C,
      different and non-interchangeable analytical methods exist. Given the fact that
      different analytical methods for the determination of creatinine and Cys C were
      used in order to validate existing GFR formulas, clinicians should be aware of
      the type used in their local laboratory. In this study, we compared GFR results
      calculated on the basis of different GFR formulas and either used Scr and Cys C
      values as determined by the analytical method originally employed for validation
      or values obtained by an alternative analytical method to evaluate any possible
      effects on the performance. METHODS: Cys C values determined by means of an
      immunoturbidimetric assay were used for calculating the GFR using equations in
      which this analytical method had originally been used for validation.
      Additionally, these same values were then used in other GFR formulas that had
      originally been validated using a nephelometric immunoassay for determining Cys
      C. The effect of using either the compatible or the possibly incompatible
      analytical method for determining Cys C in the calculation of GFR was assessed in
      comparison with the GFR measured by creatinine clearance (CrCl). RESULTS:
      Unexpectedly, using GFR equations that employed Cys C values derived from a
      possibly incompatible analytical method did not result in a significant
      difference concerning the classification of patients as having normal or reduced
      GFR compared to the classification obtained on the basis of CrCl. Sensitivity and
      specificity were adequate. On the other hand, formulas using Cys C values derived
      from a compatible analytical method partly showed insufficient performance when
      compared to CrCl. CONCLUSION: Although clinicians should be aware of applying a
      GFR formula that is compatible with the locally used analytical method for
      determining Cys C and creatinine, other factors might be more crucial for the
      calculation of correct GFR values.

PMID- 28443268
TI  - Complicated Postoperative Course after Pulmonary Artery Sling Repair and Slide
      Tracheoplasty.
AB  - Pulmonary artery sling (PAS) is a rare congenital condition in which the left
      pulmonary artery (LPA) arises from the right pulmonary artery, and then passes
      between the trachea and the esophagus to reach the left lung, thereby forming a
      sling around the airway. It is often associated with intrinsic tracheal stenosis
      due to complete cartilaginous rings. Therapeutic management nowadays consists of
      one-stage reimplantation of the LPA and tracheoplasty with cardiopulmonary bypass
      support. Here, we present a 7-week-old boy with PAS and long-segment tracheal
      stenosis (LSTS) who underwent surgical intervention consisting of reimplantation
      of the LPA and slide tracheoplasty. Multiple respiratory and cardiovascular
      complications marked the postoperative course. They consisted of recurrent failed
      attempts in weaning off mechanical ventilation due to bronchomalacia, left vocal
      cord paralysis, development of granulation tissue at the anastomosis and
      restenosis of the trachea, and the main stem bronchi requiring balloon
      dilatation. The patient also developed bilateral pulmonary artery thrombosis and
      stenosis of the LPA. After a prolonged hospitalization, the patient is doing well
      without any respiratory symptoms and has a good result on follow-up bronchoscopy
      1 year after the initial surgery. The stenosis of the LPA responded well to
      percutaneous balloon dilatation 12 months after the primary surgery. The case
      illustrates that even though surgical techniques are improving and are in general
      associated with a low morbidity and mortality, management of PAS and tracheal
      stenosis can still be challenging. However, good long-term outcome can be
      achieved if the initial postoperative phase is overcome.

PMID- 28443269
TI  - Epidemiology and Risk Assessment of Pediatric Venous Thromboembolism.
AB  - The incidence of diagnosed venous thromboembolism (VTE) has been increasing
      concurrent with advances in technology and medical care that enhance our ability
      to treat pediatric patients with critical illness or complex multiorgan system
      dysfunction. Although the overall incidence of VTE is estimated at 0.07-0.49 per
      10,000 children, higher rates are observed in specific populations including
      hospitalized children, those with central venous catheters (CVCs) or patients
      convalescing from a major surgery. While the absolute number of pediatric VTE
      events may seem trivial compared to adults, the increasing incidence, associated
      with increased mortality and morbidity, the availability of novel therapies, and
      the impact on the cost of care have made investigation of VTE risk factors and
      prevention strategies a high priority. Many putative risk factors for pediatric
      VTE have been reported, primarily from single-institution, retrospective studies
      which lack appropriate methods for verifying independent risk factors. In
      addition, some risk factors have inconsistent definitions, which vex meta
      analyses. CVCs are the most prevalent risk factors but have not consistently been
      assigned the highest level of risk as defined by odds ratios from retrospective,
      case-control studies. Few risk-assessment models for hospital-acquired pediatric
      VTE have been published. Some models focus exclusively on hospitalized pediatric
      patients, while others target specific populations such as patients with cancer
      or severe trauma. Multicenter, prospective studies are needed to identify and
      confirm risk factors in order to create a pediatric risk-assessment tool and
      optimize preventive measures and reduce unintended harm.

PMID- 28443270
TI  - Brain Lesions among Orally Fed and Gastrostomy-Fed Dysphagic Preterm Infants: Can
      Routine Qualitative or Volumetric Quantitative Magnetic Resonance Imaging Predict
      Feeding Outcomes?
AB  - INTRODUCTION: The usefulness of qualitative or quantitative volumetric magnetic
      resonance imaging (MRI) in early detection of brain structural changes and
      prediction of adverse outcomes in neonatal illnesses warrants further
      investigation. Our aim was to correlate certain brain injuries and the brain
      volume of feeding-related cortical and subcortical regions with feeding method at
      discharge among preterm dysphagic infants. MATERIALS AND METHODS: Using a
      retrospective observational study design, we examined MRI data among 43 (22 male;
      born at 31.5 +/- 0.8 week gestation) infants who went home on oral feeding or
      gastrostomy feeding (G-tube). MRI scans were segmented, and volumes of brainstem,
      cerebellum, cerebrum, basal ganglia, thalamus, and vermis were quantified, and
      correlations were made with discharge feeding outcomes. Chi-squared tests were
      used to evaluate MRI findings vs. feeding outcomes. ANCOVA was performed on the
      regression model to measure the association of maturity and brain volume between
      groups. RESULTS: Out of 43 infants, 44% were oral-fed and 56% were G-tube fed at
      hospital discharge (but not at time of the study). There was no relationship
      between qualitative brain lesions and feeding outcomes. Volumetric analysis
      revealed that cerebellum was greater (p < 0.05) in G-tube fed infants, whereas
      cerebrum volume was greater (p < 0.05) in oral-fed infants. Other brain regions
      did not show volumetric differences between groups. CONCLUSION: This study
      concludes that neither qualitative nor quantitative volumetric MRI findings
      correlate with feeding outcomes. Understanding the complexity of swallowing and
      feeding difficulties in infants warrants a comprehensive and in-depth functional
      neurological assessment.

PMID- 28443271
TI  - Refractory Urinary Incontinence in Girls: The Role of the Bladder Neck.
AB  - BACKGROUND: Prevalence of lower urinary tract dysfunction (LUTD) in children is
      between 6 and 9% with urinary incontinence (UI) being one of the most common
      symptom. VARIOUS ASPECTS OF LOWER URINARY TRACT SYMPTOMS LUTS: Anatomical
      anomalies of the urinary tract as well as neurogenic underlying pathology can
      results in LUTS. Comorbidities and long-term consequences of the LUTD for the
      female patients as well as genetic issues are also briefly discussed. THE ROLE OF
      THE BLADDER NECK: Thanks to urodynamics, we have learnt a lot about the lower
      urinary tract function, but the role of the bladder neck in the pathophysiology
      of LUTS in children is not clear. Secondary bladder neck hypertrophy is a well
      described pathology, but there is no standardized treatment for this phenomenon.
      Primary bladder neck dysfunction has already been defined by the International
      Children's Continence Society. REFRACTORY UI IN GIRLS: Uniform diagnostic
      protocols are used in these girls with UI. Treatment consists of standard
      urotherapy, additional interventions, and pharmacotherapy in selected cases.
      Those with refractory UI require careful reassessment to look for the
      unrecognized disorders. Invasive urodynamics should be done in those patients.
      Ultrasound of the bladder neck region and the pelvic floor can be helpful, but
      its interpretation is very subjective. In a small group bladder neck
      insufficiency can be found and those might benefit from a surgical intervention.
      FUTURE PERSPECTIVE: Strict criteria of the bladder neck insufficiency in children
      must be defined. Early surgical intervention in girls with bladder neck
      insufficiency might reduce the long period of intensive conservative treatment.

PMID- 28443272
TI  - 3-Dimensional Facial Analysis-Facing Precision Public Health.
AB  - Precision public health is a new field driven by technological advances that
      enable more precise descriptions and analyses of individuals and population
      groups, with a view to improving the overall health of populations. This promises
      to lead to more precise clinical and public health practices, across the
      continuum of prevention, screening, diagnosis, and treatment. A phenotype is the
      set of observable characteristics of an individual resulting from the interaction
      of a genotype with the environment. Precision (deep) phenotyping applies
      innovative technologies to exhaustively and more precisely examine the discrete
      components of a phenotype and goes beyond the information usually included in
      medical charts. This form of phenotyping is a critical component of more precise
      diagnostic capability and 3-dimensional facial analysis (3DFA) is a key
      technological enabler in this domain. In this paper, we examine the potential of
      3DFA as a public health tool, by viewing it against the 10 essential public
      health services of the "public health wheel," developed by the US Centers for
      Disease Control. This provides an illustrative framework to gage current and
      emergent applications of genomic technologies for implementing precision public
      health.

PMID- 28443273
TI  - Utilizing the "Plan, Do, Study, Act" Framework to Explore the Process of
      Curricular Assessment and Redesign in a Physical Therapy Education Program in
      Suriname.
AB  - PURPOSE: To describe how a multinational team worked together to transition a
      physical therapy (PT) educational program in Paramaribo, Suriname, from a
      Bachelor level to a Master of Science in Physical Therapy (MSPT) level. The team
      was made up of PT faculty from Anton De Kom Universiteit van Suriname (AdeKUS),
      the Flemish Interuniversity Council University Development Cooperation (VLIR-UOS)
      leadership, and Health Volunteers Overseas volunteers. In this case study, the
      process for curricular assessment, redesign, and upgrade is described
      retrospectively using a Plan, Do, Study, Act (PDSA) framework. METHOD: PT
      educational programs in developing countries are eager for upgrade to meet
      international expectations and to better meet community health-care needs. An
      ongoing process which included baseline assessment of all aspects of the existing
      bachelor's program in PT, development of a plan for a MSPT, implementation of the
      master's program, and evaluation following implementation is described.
      CONCLUSION: Curricular assessment and upgrade in resource-limited countries
      requires the implementation of process-oriented methods. The PDSA process is a
      useful tool to explore curricular development. The international collaboration
      described in this paper provides an example of the diligence, consistency, and
      dedication required to see a project through and achieve success while providing
      adequate support to the host site. This project might provide valuable insights
      for those involved in curricular redesign in similar settings.

PMID- 28443274
TI  - The Guatemala-Penn Partners: An Innovative Inter-Institutional Model for
      Scientific Capacity-Building, Healthcare Education, and Public Health.
AB  - Population health outcomes are directly related to robust public health programs,
      access to basic health services, and a well-trained health-care workforce.
      Effective health services need to systematically identify solutions,
      scientifically test these solutions, and share generated knowledge. The World
      Health Organization (WHO)'s Global Healthcare Workforce Alliance states that the
      capacity to perform research is an essential factor for well-functioning public
      health systems. Low- and middle-income countries have greater health-care worker
      shortages and lower research capacity than higher-income countries. International
      global health partnerships between higher-income countries and low-middle-income
      countries aim to directly address such inequalities through capacity building, a
      process by which human and institutional resources are strengthened and
      developed, allowing them to perform high-level functions, solve complex problems,
      and achieve important objectives. The Guatemala-Penn Partners (GPP) is a
      collaboration among academic centers in Guatemala and the University of
      Pennsylvania (Penn), in Philadelphia, Pennsylvania that echoes the vision of the
      WHO's Global Healthcare Workforce Alliance. This article describes the historical
      development and present organization of the GPP according to its three guiding
      principles: university-to-university connections, dual autonomies with locally
      led capacity building, and mutually beneficial exchanges. It describes the GPP
      activities within the domains of science, health-care education, and public
      health, emphasizing implementation factors, such as sustainability and
      scalability, in relation to the guiding principles. Successes and limitations of
      this innovative model are also analyzed in the hope that the lessons learned may
      be applied to similar partnerships across the globe.

PMID- 28443275
TI  - Integration of HIV Testing into Maternal, Newborn, and Child Health Weeks for
      Improved Case Finding and Linkage to Prevention of Mother-to-Child Transmission
      Services in Benue State, Nigeria.
AB  - BACKGROUND: In Nigeria, maternal, newborn, and child health (MNCH) weeks are
      campaign-like events designed to accelerate progress toward Millennium
      Development Goals. The authors examined whether integrating HIV testing into MNCH
      weeks was feasible and could lead to increased case finding and linkage to
      prevention of mother-to-child transmission (PMTCT) services. METHODS: Pregnant
      women attending MNCH week during the first week of December 2014 in 13 local
      government areas in Benue State were provided with HIV tests and referrals to
      PMTCT services. Demographic, past antenatal care (ANC), and HIV testing
      information were collected using a structured questionnaire. We used routine
      ANC/PMTCT data from national electronic system (DHIS-2) to compare with the
      results obtained from MNCH week. RESULTS: A total of 50,271 pregnant women with a
      median age of 25 years (IQR: 21-29) were offered HIV testing. About 50,253
      (99.96%) agreed to get HIV testing, with 1,063 (2.1%) testing positive. Six
      hundred forty-four (60.6%) of those with positive results were linked to PMTCT.
      In multivariate analysis, marital status, gestation age, and those with no ANC
      visit during this pregnancy were associated with a positive HIV test.
      Approximately 30% (50,253 versus 39,080) more pregnant women received HIV testing
      in MNCH week compared to those who received HIV testing in routine ANC services
      in 2013. Of the 50,253 who accepted testing, 15,611 (31.1%) did not attend ANC
      during this pregnancy, of which 9,615 (61.6%) had not had any previous HIV tests.
      Four hundred forty-two (4.6%) of these 9,615 tested HIV-positive. CONCLUSION:
      Integration of HIV testing into MNCH weeks is feasible and improved uptake of HIV
      testing and linkage to care. However, the rate of HIV positivity was lower than
      that reported by previous studies. The findings indicate that MNCH weeks provides
      opportunity to reach those who do not attend ANC services for HIV care.

PMID- 28443276
TI  - Commentary: Adverse Childhood Experiences and Risk for Suicidal Behavior in Male
      Iraq and Afghanistan Veterans Seeking PTSD Treatment.

PMID- 28443277
TI  - Pediatric Hand Surgery Training in Nicaragua: A Sustainable Model of Surgical
      Education in a Resource-Poor Environment.
AB  - Recent reports have demonstrated that nearly two-thirds of the world's population
      do not have access to adequate surgical care, a burden that is borne
      disproportionately by residents of resource-poor countries. Although the reasons
      for limited access to surgical care are complex and multi-factorial, among the
      most substantial barriers is the lack of trained surgical providers. This is
      particularly true in surgical subspecialties that focus on life-improving, rather
      than life-saving, treatments, such as pediatric hand and upper extremity surgery,
      which manages such conditions as congenital malformations, trauma and post
      traumatic deformities including burns, and neuromuscular conditions (brachial
      plexus birth palsy, spinal cord injury, and cerebral palsy). Many models of
      providing surgical care in resource-limited environments have been described and
      implemented, but few result in sustainable models of health-care delivery. We
      present our experience developing a pediatric hand and upper extremity surgery
      training program in Nicaragua, a resource-limited nation, that grew out of a
      collaboration of American and Nicaraguan orthopedic surgeons. We compare this
      experience to that of surgeons undergoing subspecialty training in pediatric
      upper limb surgery in the US, highlighting the similarities and differences of
      these training programs. Finally, we assess the results of this training program
      and identify areas for further growth and development.

PMID- 28443278
TI  - Saliva Liquid Biopsy for Point-of-Care Applications.
AB  - Saliva is a non-invasive biofluid, which is easy to collect, transport, and
      store. Because of its accessibility and connection to systemic diseases, saliva
      is one of the best candidates for the advancement of point-of-care medicine,
      where individuals are able to easily monitor their health status by using
      portable convenient tools such as smartphones. There are a variety of scenarios
      with which saliva can be used: studies have been conducted on using saliva to
      measure stress hormones, enzyme levels, developmental disease biomarkers, and
      even cancer mutations. If validated biomarkers were combined with high-quality
      detection tools, saliva would open up a new frontier in high-quality healthcare,
      allowing physicians and patients to work together for real-time health monitoring
      and high-impact personalized preventative medicine. One of the most exciting
      emerging frontiers of saliva is liquid biopsy, which is a non-invasive means to
      assess the presence and characteristics of cancer in a patient. This article will
      review current basic knowledge of biomarkers, review their relation to different
      diseases and conditions, and explore liquid biopsy for point-of-care
      applications.

PMID- 28443279
TI  - Analogs of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider
      Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the
      Parental Peptide.
AB  - The frog skin-derived peptide Temporin 1Tb (TB) has gained increasing attention
      as novel antimicrobial agent for the treatment of antibiotic-resistant and/or
      biofilm-mediated infections. Nevertheless, such a peptide possesses a
      preferential spectrum of action against Gram-positive bacteria. In order to
      improve the therapeutic potential of TB, the present study evaluated the
      antibacterial and antibiofilm activities of two TB analogs against medically
      relevant bacterial species. Of the two analogs, TB_KKG6A has been previously
      described in the literature, while TB_L1FK is a new analog designed by us through
      statistical-based computational strategies. Both TB analogs displayed a faster
      and stronger bactericidal activity than the parental peptide, especially against
      Gram-negative bacteria in planktonic form. Differently from the parental peptide,
      TB_KKG6A and TB_L1FK were able to inhibit the formation of Staphylococcus aureus
      biofilms by more than 50% at 12 MUM, while only TB_KKG6A prevented the formation
      of Pseudomonas aeruginosa biofilms at 24 MUM. A marked antibiofilm activity
      against preformed biofilms of both bacterial species was observed for the two TB
      analogs when used in combination with EDTA. Analysis of synergism at the cellular
      level suggested that the antibiofilm activity exerted by the peptide-EDTA
      combinations against mature biofilms might be due mainly to a disaggregating
      effect on the extracellular matrix in the case of S. aureus, and to a direct
      activity on biofilm-embedded cells in the case of P. aeruginosa. Both analogs
      displayed a low hemolytic effect at the active concentrations and, overall,
      TB_L1FK resulted less cytotoxic toward mammalian cells. Collectively, the results
      obtained demonstrated that subtle changes in the primary sequence of TB may
      provide TB analogs that, used alone or in combination with adjuvant molecules
      such as EDTA, exhibit promising features against both planktonic and biofilm
      cells of medically relevant bacteria.

PMID- 28443280
TI  - In vivo Reprogramming of Cancer Metabolism by MYC.
AB  - The past few decades have welcomed tremendous advancements toward understanding
      the functional significance of altered metabolism during tumorigenesis. However,
      many conclusions drawn from studies of cancer cells in a dish (i.e., in vitro)
      have been put into question as multiple lines of evidence have demonstrated that
      the metabolism of cells can differ significantly from that of primary tumors (in
      vivo). This realization, along with the need to identify tissue-specific
      vulnerabilities of driver oncogenes, has led to an increased focus on oncogene
      dependent metabolic programming in vivo. The oncogene c-MYC (MYC) is
      overexpressed in a wide variety of human cancers, and while its ability to alter
      cellular metabolism is well-established, translating the metabolic requirements,
      and vulnerabilities of MYC-driven cancers to the clinic has been hindered by
      disparate findings from in vitro and in vivo models. This review will provide an
      overview of the in vivo strategies, mechanisms, and conclusions generated thus
      far by studying MYC's regulation of metabolism in various cancer models.

PMID- 28443281
TI  - MYC and AMPK-Save Energy or Die!
AB  - MYC sustains non-stop proliferation by altering metabolic machinery to support
      growth of cell mass. As part of the metabolic transformation MYC promotes lipid,
      nucleotide and protein synthesis by hijacking citric acid cycle to serve
      biosynthetic processes, which simultaneously exhausts ATP production. This leads
      to the activation of cellular energy sensing protein, AMP-activated protein
      kinase (AMPK). Cells with normal growth control can stop cell proliferation
      machinery to replenish ATP reservoirs whereas MYC prevents such break by blocking
      the cell cycle exit. The relentless cell cycle activation, accompanied by
      sustained metabolic stress and AMPK activity, switches the energy-saving AMPK to
      pro-apoptotic AMPK. The AMPK-involving metabolic side of MYC apoptosis may
      provide novel avenues for therapeutic development. Here we first review the role
      of anabolic MYC and catabolic AMPK pathways in context of cancer and then discuss
      how the concomitant activity of both pathways in tumor cells may result in
      targetable synthetic lethal vulnerabilities.

PMID- 28443283
TI  - Vascular Access Site for Renal Replacement Therapy in Acute Kidney Injury: A Post
      hoc Analysis of the ATN Study.
AB  - BACKGROUND: Acute kidney injury requiring renal replacement therapy (RRT) in the
      intensive care unit portends a poor prognosis. The decisions regarding dialysis
      catheter placement is based mainly on physician discretion with little evidence
      to support the choice of dialysis catheter location. METHODS: The Veterans
      Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was
      a multicenter, prospective, randomized trial of intensive vs. less intensive RRT
      in critically ill patients with AKI. We assessed the association of dialysis
      catheter location with dialysis catheter-related outcomes including catheter
      related complications, mortality, dialysis dependence, and dialysis dose
      delivered. RESULTS: Of the 1,124 patients enrolled in the ATN study, catheter
      data were available in 1,016 (90.39%) patients. A total of 91 (8.96%) subclavian,
      387 (38.09%) internal jugular, and 538 (52.95%) femoral dialysis catheters were
      inserted. The femoral group was younger (58.39 +/- 16.27), had greater bleeding
      tendency [lower platelet count (96.00 +/- 109.35) with higher INR (2.01 +/-
      2.19)], and had a higher baseline sequential organ failure assessment score on
      admission (14.59 +/- 3.61) compared to the other two groups. Dialysis catheter
      related complications were low in this study with no significant difference in
      the rates of complications among all catheter locations. Mortality and dialysis
      dependence was lowest in the subclavian group, while the dose of dialysis
      delivered (Kt/V) remained lowest in the femoral group, after propensity score and
      center adjustments. CONCLUSION: Patient characteristics influence the choice of
      dialysis catheter location with a tendency to place femoral catheters in younger,
      sicker, and more coagulopathic patients. There were no statistically significant
      differences in complication rates among the three catheter locations, although
      femoral catheters may be associated with a lower delivered dose of dialysis
      during intermittent hemodialysis. CLINICAL TRIAL REGISTRATION:
      www.ClinicalTrials.gov, identifier NCT00076219.

PMID- 28443282
TI  - Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer.
AB  - Over the past decade, major advances have been made in the management of advanced
      non-small cell lung cancer (NSCLC). There has been a particular focus on the
      identification and targeting of putative driver aberrations, which has propelled
      NSCLC to the forefront of precision medicine. Several novel molecularly targeted
      agents have now achieved regulatory approval, while many others are currently in
      late-phase clinical trial testing. These antitumor therapies have significantly
      impacted the clinical outcomes of advanced NSCLC and provided patients with much
      hope for the future. Despite this, multiple deficiencies still exist in our
      knowledge of this complex disease, and further research is urgently required to
      overcome these critical issues. This review traces the path undertaken by the
      different therapeutics assessed in NSCLC and the impact of precision medicine in
      this disease. We also discuss the areas of "imprecision" that still exist in
      NSCLC and the modern hypothesis-testing studies being conducted to address these
      key challenges.

PMID- 28443286
TI  - Editorial: Personalized Medicine and Neurosurgery.

PMID- 28443284
TI  - Fecal Short-Chain Fatty Acid Variations by Breastfeeding Status in Infants at 4
      Months: Differences in Relative versus Absolute Concentrations.
AB  - Our gut microbiota provide a number of important functions, one of which is the
      metabolism of dietary fiber and other macronutrients that are undigested by the
      host. The main products of this fermentation process are short-chain fatty acids
      (SCFAs) and other intermediate metabolites including lactate and succinate.
      Production of these metabolites is dependent on diet and gut microbiota
      composition. There is increasing evidence for the role of SCFAs in host
      physiology and metabolic processes as well as chronic inflammatory conditions
      such as allergic disease and obesity. We aimed to investigate differences in
      fecal SCFAs and intermediate metabolites in 163 infants at 3-5 months of age
      according to breastfeeding status. Compared to no exposure to human milk at time
      of fecal sample collection, exclusive breastfeeding was associated with lower
      absolute concentrations of total SCFAs, acetate, butyrate, propionate, valerate,
      isobutyrate, and isovalerate, yet higher concentrations of lactate. Further, the
      relative proportion of acetate was higher with exclusive breastfeeding. Compared
      to non-breastfed infants, those exclusively breastfed were four times more likely
      (aOR 4.50, 95% CI 1.58-12.82) to have a higher proportion of acetate relative to
      other SCFAs in their gut. This association was independent of birth mode,
      intrapartum antibiotics, infant sex, age, recruitment site, and maternal BMI or
      socioeconomic status. Our study confirms that breastfeeding strongly influences
      the composition of fecal microbial metabolites in infancy.

PMID- 28443285
TI  - High-grade Gliomas Exhibit Higher Peritumoral Fractional Anisotropy and Lower
      Mean Diffusivity than Intracranial Metastases.
AB  - Differentiating high-grade gliomas and intracranial metastases through non
      invasive imaging has been challenging. Here, we retrospectively compared both
      intratumoral and peritumoral fractional anisotropy (FA), mean diffusivity (MD),
      and fluid-attenuated inversion recovery (FLAIR) measurements between high-grade
      gliomas and metastases. Two methods were utilized to select peritumoral region of
      interest (ROI). The first method utilized the manual placement of four ROIs
      adjacent to the lesion. The second method utilized a semiautomated and
      proprietary MATLAB script to generate an ROI encompassing the entire tumor. The
      average peritumoral FA, MD, and FLAIR values were determined within the ROIs for
      both methods. Forty patients with high-grade gliomas and 44 with metastases were
      enrolled in this study. Thirty-five patients with high-grade glioma and 30
      patients with metastases had FLAIR images. There was no significant difference in
      age, gender, or race between the two patient groups. The high-grade gliomas had a
      significantly higher tumor-to-brain area ratio compared to the metastases. There
      were no differences in average intratumoral FA, MD, and FLAIR values between the
      two groups. Both the manual sample method and the semiautomated peritumoral ring
      method resulted in significantly higher peritumoral FA and significantly lower
      peritumoral MD in high-grade gliomas compared to metastases (p < 0.05). No
      significant difference was found in FLAIR values between the two groups
      peritumorally. Receiver operating curve analysis revealed FA to be a more
      sensitive and specific metric to differentiate high-grade gliomas and metastases
      than MD. The differences in the peritumoral FA and MD values between high-grade
      gliomas and metastases seemed due to the infiltration of glioma to the
      surrounding brain parenchyma.

PMID- 28443287
TI  - Brachial Approach As an Alternative Technique of Fibrin Sheath Removal for
      Implanted Venous Access Devices.
AB  - Implanted venous access device (IVAD) late dysfunction is commonly caused by
      fibrin sheath formation. The standard method of endovascular fibrin sheath
      removal is performed via the femoral vein. However, it is not always technically
      feasible and sometimes contraindicated. Moreover, approximately 4-6 h of bed rest
      is necessary after the procedure. In this article, we describe an alternative
      method of fibrin sheath removal using the brachial vein approach in a young woman
      receiving chemotherapy for breast cancer. The right basilic vein was punctured,
      and a long 6 degrees F introducer sheath was advanced into the right subclavian
      vein. Endovascular maneuvers consisted on advancing AtrieveTM Vascular Snare 15-9
      mm after catheter insertion in the superior vena cava through a 5.2 degrees F
      Judkins left catheter. IVAD patency was restored without any complication, and
      the patient was discharged immediately after the procedure. In conclusion, fibrin
      sheath removal from an obstructed IVAD could be performed via the right brachial
      vein. Further research is necessary in order to prove efficacy of this technique.

PMID- 28443288
TI  - Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the
      Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by
      Rubisco activase for efficient function. Rubisco mediates the fixation of
      atmospheric CO2 by catalyzing the carboxylation of the five-carbon sugar ribulose
      1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to
      increase crop yields by bioengineering Rubisco remain unsuccessful. This is due
      in part to the complex cellular machinery required for Rubisco biogenesis and
      metabolic maintenance. To function, Rubisco must undergo an activation process
      that involves carboxylation of an active site lysine by a non-substrate CO2
      molecule and binding of a Mg2+ ion. Premature binding of the substrate RuBP
      results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range
      of sugar phosphates, some of which are "misfire" products of its multistep
      catalytic reaction. The release of the inhibitory sugar molecule is mediated by
      the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the
      structural remodeling of Rubisco. Rca enzymes are found in the vast majority of
      photosynthetic organisms, from bacteria to higher plants. They share a canonical
      AAA+ domain architecture and form six-membered ring complexes but are diverse in
      sequence and mechanism, suggesting their convergent evolution. In this review, we
      discuss recent advances in understanding the structure and function of this
      important group of client-specific AAA+ proteins.

PMID- 28443289
TI  - Frequency and Duration of Fecal Shedding of Salmonella Enteritidis by
      Experimentally Infected Laying Hens Housed in Enriched Colony Cages at Different
      Stocking Densities.
AB  - Human infections with Salmonella Enteritidis are often attributed to the
      consumption of contaminated eggs, so the prevalence of this pathogen in egg
      laying poultry is an important public health risk factor. Numerous and complex
      environmental influences on Salmonella persistence and transmission are exerted
      by management practices and housing facilities used in commercial egg production.
      In recent years, the animal welfare implications of poultry housing systems have
      guided the development of alternatives to traditional cage-based housing, but
      their food safety consequences are not yet fully understood. The present study
      assessed the effects of different bird stocking densities on the frequency and
      duration of fecal shedding of S. Enteritidis in groups of experimentally infected
      laying hens housed in colony cages enriched with perching and nesting areas. In
      two trials, groups of laying hens were distributed at two stocking densities (648
      and 973 cm2/bird) into enriched colony cages and (along with a group housed in
      conventional cages at 648 cm2/bird) orally inoculated with doses of 1.0 * 108 cfu
      of S. Enteritidis. At 10 weekly postinoculation intervals, samples of voided
      feces were collected from beneath each cage and cultured to detect S.
      Enteritidis. Fecal shedding of S. Enteritidis was detected for up to 10 weeks
      postinoculation by hens in all three housing treatment groups. The overall
      frequency of positive fecal cultures was significantly (P < 0.05) greater from
      conventional cages than from enriched colony cages (at the lower stocking
      density) for the total of all sampling dates (45.0 vs. 33.3%) and also for
      samples collected at 4-9 weeks postinfection. Likewise, the frequency of S.
      Enteritidis isolation from feces from conventional cages was significantly
      greater than from enriched colony cages (at the higher hen stocking density) for
      the sum of all samples (45.0 vs. 36.7%) and at 6 weeks postinoculation. Moreover,
      the frequency of S. Enteritidis fecal recovery from enriched colony cages at the
      higher hen stocking was significantly greater than from similar cages at the
      lower stocking density for all 10 sampling dates combined (39.4 vs. 33.3%). These
      results suggest that stocking density can affect S. Enteritidis intestinal
      colonization and fecal shedding in laying hens, but some other difference between
      conventional and enriched colony cage systems appears to exert an additional
      influence.

PMID- 28443290
TI  - Comparison of a Supraglottic Airway Device (v-gel(r)) with Blind Orotracheal
      Intubation in Rabbits.
AB  - INTRODUCTION: Achieving a secure airway in rabbits is generally considered more
      difficult than in cats or dogs. Their relatively large tongue, small
      oropharyngeal cavity and glottis limit direct visualization. A rabbit-specific
      supraglottic airway device (SGAD) may offer benefits over blind orotracheal
      intubation. ANIMALS AND METHODS: Fifteen adult New Zealand white rabbits were
      randomized to SGAD or orotracheal intubation (ETT). All animals were sedated with
      dexmedetomidine (0.1 mg kg-1 IM) and midazolam (0.5 mg kg-1 IM), followed by
      induction with alfaxalone (0.3 mg kg-1 IV). Two CT scans of the head and neck
      were performed, following sedation and SGAD/ETT placement. The following were
      recorded: time to successful device insertion, smallest cross-sectional airway
      area, airway sealing pressure, and histological score of tracheal tissue. Data
      were analyzed with a Mann-Whitney test. RESULTS: Two rabbits were excluded
      following failed ETT. Body masses were similar [ETT; n = 6, 2.6 (2.3-4.5) kg,
      SGAD; n = 7, 2.7 (2.4-5.0) kg]. SGAD placement was significantly faster [33 (14
      38) s] than ETT [59 (29-171) s]. Cross-sectional area (CSA) was significantly
      reduced from baseline [12.2 (6.9-3.4) mm2] but similar between groups [SGAD; 2.7
      (2.0-12.3) mm2, ETT; 3.8 (2.3-6.6) mm2]. In the SGAD group, the device tip
      migrated into the laryngeal vestibule in 6/7 rabbits, reducing the CSA. ETT
      airway seals were higher [15 (10-20) cmH2O], but not significant [SGAD; 5 (5-20)
      cmH2O, p = 0.06]. ETT resulted in significantly more mucosal damage [histological
      score 3.3 (1.0-5.0)], SGAD; 0.67 (0.33-3.67). CONCLUSION: The SGAD studied was
      faster to place and caused less damage than orotracheal intubation, but resulted
      in a similar CSA.

PMID- 28443292
TI  - Measurements of metastatic renal cell tumours as determined by diffusion weighted
      imaging or computed tomography are in close agreement, a pilot study.
AB  - BACKGROUND: Diffusion weighted magnetic resonance imaging (DWI) provides both
      functional and anatomical information regarding tumours but can also be used for
      tumour detection. Today, tumour treatment response in clinical trials is mainly
      assessed on Computed Tomography (CT) using established criteria. Despite
      availability of dedicated software, CT still requires significant manual work for
      selection and measurement in treatment response evaluation of solid tumours.
      PURPOSE: To compare the maximum diameter of tumour lesions on CT with the
      corresponding measurements on diffusion weighted images. MATERIALS AND METHODS:
      In this prospective cohort, metastatic lesions were identified on CT and on DWI
      in five patients with metastatic renal cell carcinoma before and after three
      months of treatment with pazopanib. Two radiologists independently measured the
      same lesions on axial CT images and separately also on axial DWI images. The
      measurements were compared between CT and DWI with respect to the number of
      target lesions measured, size of the lesions, size reduction due to treatment and
      the inter-observer variability. Wilcoxon signed rank test, linear regression and
      Bland-Altman plots were used for statistical analyses. RESULTS: In this pilot
      study, there was no significant inter-observer variability in terms of numbers of
      lesion selected between CT and DWI. A significant reduction of lesion size was
      observed both for CT and DWI when post-treatment scans were compared to pre
      treatment scans. There was no significant difference in measurement of lesion
      size on both pre- and post treatment scans between CT and DWI (p = 0.099 and p =
      0.388 respectively). CONCLUSION: Measurement of the size of metastatic lesions on
      the basis of axial DWI images are in close agreement with measurement based on
      conventional axial CT images, the most often employed approach in clinical trials
      today. The results in this pilot study can be used to estimate sufficient sample
      size in a larger trial with adequate power, were the results can be confirmed in
      a wider range of cancers other than renal cell carcinoma.

PMID- 28443293
TI  - Dataset of effect of Wogonin, a natural flavonoid, on the viability and
      activation of NF-kappaB and MAPKs in IL-1beta-stimulated human OA chondrocytes.
AB  - This article contains data related to the article "Wogonin, a plant derived small
      molecule exerts potent anti-inflammatory and chondroprotective effects through
      activation of ROS/ERK/Nrf2 signaling pathways in human Osteoarthritis
      chondrocytes" (Khan et al. 2017) [1]. The data are related to effects of Wogonin
      on the viability and IL-1beta-stimulated activation of NF-kappaB and ERK1/2,
      JNK1/2 and p38 MAPKs in human OA chondrocytes. Gene expression data representing
      the chondrogenic phenotype and the efficiency of Nrf2 knockdown in monolayer
      culture of human OA chondrocytes were shown. Moreover, mass spectrometric
      calibration curve of Wogonin used to quantify the intracellular uptake were also
      presented. The data are presented in the form of figures and significance of
      these has been given in the research article (Khan et al. 2017) [1].

PMID- 28443294
TI  - Dataset on records of Hericium erinaceus in Slovakia.
AB  - The data presented in this article are related to the research article entitled
      "Habitat preferences of Hericium erinaceus in Slovakia" (Kunca and Ciliak, 2016)
      [FUNECO607] [2]. The dataset include all available and unpublished data from
      Slovakia, besides the records from the same tree or stem. We compiled a database
      of records of collections by processing data from herbaria, personal records and
      communication with mycological activists. Data on altitude, tree species, host
      tree vital status, host tree position and intensity of management of forest
      stands were evaluated in this study. All surveys were based on basidioma
      occurrence and some result from targeted searches.

PMID- 28443291
TI  - A review of the development of tumor vasculature and its effects on the tumor
      microenvironment.
AB  - BACKGROUND: The imbalance of angiogenic regulators in tumors drives tumor
      angiogenesis and causes the vasculature to develop much differently in tumors
      than in normal tissue. There are several cancer therapy techniques currently
      being used and developed that target the tumor vasculature for the treatment of
      solid tumors. This article reviews the aspects of the tumor vasculature that are
      relevant to most cancer therapies but particularly to vascular targeting
      techniques. MATERIALS AND METHODS: We conducted a review of identified
      experiments in which tumors were transplanted into animals to study the
      development of the tumor vasculature with tumor growth. Quantitative vasculature
      morphology data for spontaneous human head and neck cancers are reviewed.
      Parameters assessed include the highest microvascular density (h-MVD) and the
      relative vascular volume (RVV). The effects of the vasculature on the tumor
      microenvironment are discussed, including the distributions of hypoxia and
      proliferation. RESULTS: Data for the h-MVD and RVV in head and neck cancers are
      highly varied, partly due to methodological differences. However, it is clear
      that the cancers are typically more vascularized than the corresponding normal
      tissue. The commonly observed chronic hypoxia and acute hypoxia in these tumors
      are due to high intratumor heterogeneity in MVD and lower than normal blood
      oxygenation levels through the abnormally developed tumor vasculature. Hypoxic
      regions are associated with decreased cell proliferation. CONCLUSION: The
      morphology of the vasculature strongly influences the tumor microenvironment,
      with important implications for tumor response to medical intervention such as
      radiotherapy. Quantitative vasculature morphology data herein may be used to
      inform computational models that simulate the spatial tumor vasculature. Such
      models may play an important role in exploring and optimizing vascular targeting
      cancer therapies.

PMID- 28443295
TI  - Data for discriminating dead/live bacteria in homogenous cell suspensions and the
      effect of insoluble substrates on turbidimetric measurements.
AB  - Estimation of bacterial growth by rapid traditional methods such as
      spectrophometric measurements at 600 nm (OD600) is not applicable for cultures
      containing insoluble particles in the growth media. Colony counts are the only
      suitable alternative but these are laborious and not high-throughput. The data
      presented in this article is related to the research article entitled "Two-colour
      fluorescence fluorimetric analysis for direct quantification of bacteria and its
      application in monitoring bacterial growth in cellulose degradation systems"
      (Duedu and French, 2017) [1]. This data article presents original primary data
      describing the discrimination of dead/live bacteria in homogenous cell
      suspensions and how the presence of insoluble substrates affect the turbidity of
      the suspensions.

PMID- 28443296
TI  - Data of sperm-entry inability in Drosophila melanogaster ovarian follicles that
      are depleted of s36 chorionic protein.
AB  - This paper presents data associated with the research article entitled "Targeted
      downregulation of s36 protein unearths its cardinal role in chorion biogenesis
      and architecture during Drosophila melanogaster oogenesis" [1]. Drosophila
      chorion is produced by epithelial follicle cells and one of its functional
      serving role is egg fertilization through the micropyle, a specialized narrow
      channel at the anterior tip of the egg [2]. Sperm entry during fertilization is
      necessary for the egg to complete meiosis [3]. D. melanogaster flies being
      characterized by severe downregulation of the s36 chorionic protein, specifically
      in the follicle-cell compartment of their ovary, appear with impaired fly
      fertility (Velentzas et al., 2016) [1]. In an effort to further investigate
      whether the observed infertility in the s36-targeted flies derives from a
      fertilization failure, such as the inability of sperm to pass through egg's
      micropyle, we mated females carrying s36-depleted ovaries with males expressing
      the GFP protein either in their sperm tails, or in both their sperm tails and
      sperm heads.

PMID- 28443297
TI  - Data on multiple body parameters, microclimatic variables, and subjective
      assessment of thermal sensation monitored in outdoor environment.
AB  - This paper describes two sets of data on multiple body parameters of five
      participants, on microclimatic variables, and on self-reported assessment of
      thermal responses, all monitored in the same outdoor urban environment. Data were
      collected during three seasons, summer, autumn and winter 2010-2011, in the city
      of Athens, Greece. Part of these data, collected during the summer period, is
      related to the research article entitled "Case study of skin temperature and
      thermal perception in a hot outdoor environment." (Pantavou et al., 2014) [1].

PMID- 28443298
TI  - Data on changes in red wine phenolic compounds, headspace aroma compounds and
      sensory profile after treatment of red wines with activated carbons with
      different physicochemical characteristics.
AB  - Data in this article presents the changes on phenolic compounds, headspace aroma
      composition and sensory profile of a red wine spiked with 4-ethylphenol and 4
      ethylguaiacol and treated with seven activated carbons with different
      physicochemical characteristics, namely surface area, micropore volume and
      mesopore volume ("Reduction of 4-ethylphenol and 4-ethylguaiacol in red wine by
      activated carbons with different physicochemical characteristics: impact on wine
      quality" Filipe-Ribeiro et al. (2017) [1]). Data on the physicochemical
      characteristics of the activated carbons are shown. Statistical data on the
      sensory expert panel consistency by General Procrustes Analysis is shown.
      Statistical data is also shown, which correlates the changes in chemical
      composition of red wines with the physicochemical characteristics of activated
      carbons used.

PMID- 28443299
TI  - Data on the mRNA expression by in situ hybridization of Wnt signaling pathway
      members in the mouse uterus.
AB  - Wnt signaling plays an important role in uterine organogenesis and oncogenesis.
      Our mRNA expression data documents the expression of various Wnt pathway members
      during the key stages of uterine epithelial gland development. Our data
      illustrates the expression of Wnt signaling inhibitors (Axin2, Sfrp2, Sfrp4, Dkk1
      and Dkk3) in mice uteri at postnatal day 6 (PND 6) and day 15 (PND 15). They also
      describe the expression pattern of the Wnt ligands (Wnt1, Wnt2, Wnt2b, Wnt3,
      Wnt3a, Wnt5b, Wnt7b, Wnt8a, Wnt8b, Wnt9a, Wnt9b, Wnt10a and Wnt10b) in mice uteri
      with or without progesterone treatment. Detailed interpretation and discussion of
      these data is presented in the research article entitled "Differential Wnt
      signaling activity limits epithelial gland development to the anti-mesometrial
      side of the mouse uterus" [1].

PMID- 28443301
TI  - Rare presentation of Rothmund-Thomson syndrome with predominantly cutaneous
      findings.

PMID- 28443300
TI  - The 6-year follow-up of a Japanese patient with silent erythropoietic
      protoporphyria.

PMID- 28443302
TI  - Successful treatment of severe anti-p200 pemphigoid in a heart transplant
      recipient with a single cycle of rituximab.

PMID- 28443303
TI  - Cutaneous ulceration and breast implant compromise after pulse dye laser for
      radiation-induced telangiectasias.

PMID- 28443304
TI  - Radiation-induced hidradenitis suppurativa: A case report.

PMID- 28443305
TI  - Talimogene laherparepvec for regionally advanced Merkel cell carcinoma: A report
      of 2 cases.

PMID- 28443306
TI  - Gemcitabine-associated acute lipodermatosclerosislike eruption: An
      underrecognized phenomenon.

PMID- 28443307
TI  - Complete durable remission of a fulminant primary cutaneous aggressive
      epidermotropic CD8+ cytotoxic T-cell lymphoma after autologous and allogeneic
      hematopoietic stem cell transplantation.

PMID- 28443308
TI  - Plasmablasticlike lymphoma arising within chronic pyoderma gangrenosum.

PMID- 28443309
TI  - Touch preparation for the rapid diagnosis of disseminated aspergillosis.

PMID- 28443310
TI  - Keratosis lichenoides chronica successfully treated with isotretinoin and
      methotrexate.

PMID- 28443312
TI  - Erythema elevatum diutinum-associated with loss of the uvula.

PMID- 28443313
TI  - Acrodermatitis of Hallopeau and erosive oral mucositis successfully treated with
      secukinumab.

PMID- 28443311
TI  - Nivolumab-related cutaneous sarcoidosis in a patient with lung adenocarcinoma.

PMID- 28443314
TI  - Cutaneous Yarrowia lipolytica infection in an immunocompetent woman.

PMID- 28443315
TI  - Metastatic basal cell carcinoma with loss of p63 and mismatch repair proteins.

PMID- 28443316
TI  - Extranodal natural killer/T-cell lymphoma, nasal type: A rare but critical
      diagnosis.

PMID- 28443317
TI  - Novel use of apremilast for adjunctive treatment of recalcitrant pyoderma
      gangrenosum.

PMID- 28443318
TI  - Peritoneal tuberculosis in the setting of ustekinumab treatment for psoriasis.

PMID- 28443319
TI  - Multifocal Rosai-Dorfman disease with involvement of the pinna.

PMID- 28443320
TI  - Methotrexate-induced cutaneous ulceration in 3 nonpsoriatic patients: Report of a
      rare side effect.

PMID- 28443321
TI  - The gynecologic oncology fellowship interview process: Challenges and potential
      areas for improvement.
AB  - The application and interview process for gynecologic oncology fellowship is
      highly competitive, time-consuming and expensive for applicants. We conducted a
      survey of successfully matched gynecologic oncology fellowship applicants to
      assess problems associated with the interview process and identify areas for
      improvement. All Society of Gynecologic Oncology (SGO) list-serve members who
      have participated in the match program for gynecologic oncology fellowship were
      asked to complete an online survey regarding the interview process. Linear
      regression modeling was used to examine association between year of match, number
      of programs applied to, cost incurred, and overall satisfaction. Two hundred and
      sixty-nine eligible participants reported applying to a mean of 20 programs
      [range 1-45] and were offered a mean of 14 interviews [range 1-43]. They spent an
      average of $6000 [$0-25,000], using personal savings (54%), credit cards (50%),
      family support (12%) or personal loans (3%). Seventy percent of respondents
      identified the match as fair, and 93% were satisfied. Interviewees spent a mean
      of 15 [0-45] days away from work and 37% reported difficulty arranging coverage.
      Linear regression showed an increase in number of programs applied to and cost
      per applicant over time (p < 0.001) between 1993 and 2016. Applicants who applied
      to all available programs spent more (p < 0.001) than those who applied to
      programs based on their location or quality. The current fellowship match was
      identified as fair and satisfying by most respondents despite being time
      consuming and expensive. Suggested alternative options included clustering
      interviews geographically or conducting preliminary interviews at the SGO Annual
      Meeting.

PMID- 28443322
TI  - Crassulacean acid metabolism as a continuous trait: variability in the
      contribution of Crassulacean acid metabolism (CAM) in populations of Portulacaria
      afra.
AB  - Portulacaria afra L. is a dominant facultative CAM species growing in the
      Southeastern Cape of South Africa. P. afra is well adapted to regions of the
      Spekboom thicket in areas of limited and sporadic rainfall. P. afra populations
      occur in isolated drainages. We hypothesized the utilization of CAM would vary in
      the different populations in response to rainfall and temperature gradients.
      Carbon isotope composition can be used to determine the contribution of CAM in
      leaf tissue. P. afra leaves of populations were analyzed in transects running
      south to north and east to west in locations from the coast to elevations of 1400
      m. Carbon isotope values ranged from -16.10/00 in Plutosvale to -21.00/00 to 
      22.70/00 in Port Alfred and Grahamstown populations respectively with some values
      reaching -25.20/00. These values indicated an estimated variable contribution of
      the CAM pathway ranging from 23% to almost 60%. The results indicate a much
      greater range of variability than previously reported. The carbon isotope values
      showed no direct correlation with rainfall or maximum or minimum day/night
      temperatures in the summer or winter for the different locations. The results
      indicated the microclimate may play a more significant role in determining CAM
      utilization. We present evidence that CAM is a continuous trait in P. afra and
      CAM is operating continuously at low levels during C3 photosynthesis which may
      explain the high variability in its carbon isotope composition. P. afra
      populations illustrate a large phenotypic plasticity and further studies may
      indicate genotypic differences between populations. This may be valuable in
      ascertaining the genetic contribution to its water use efficiency and possible
      use in engineering higher water use efficiency in C3 plants. The results revealed
      here may explain P. afra's ability to sequester carbon at high rates compared to
      more mesic species.

PMID- 28443323
TI  - Prevalence of CTR1 and ERCC1 Polymorphisms and Response of Biliary Tract Cancer
      to Gemcitabine-Platinum Chemotherapy
AB  - Purpose: Biliary tract cancer (BTC)is an aggressive disease with a poor
      prognosis. Most patients are diagnosed atan advanced stage for which curative
      surgery is not possible and gemcitabine-platinum chemotherapy is the treatment
      ofchoice for advanced cases. Several studies had focused on biomarkers to predict
      response from platinum drugs in lungcancer, but information is limited for BTC.
      In this study, two single nucleotide polymorphisms (SNPs) in the
      coppertransporter (CTR1) and excision repair cross-complementary group 1 (ERCC1)
      genes were investigated as predictivebiomarkers of objective response to
      gemcitabine-platinum. Methods: This cohort study aimed to assess any
      associationsof genetic polymorphisms of these proteins active in drug pathway
      with treatment response in advanced BTC patients.Twenty six patients were
      enrolled. DNA was extracted from peripheral blood and genetic polymorphisms were
      assessedby Taqman allelic discrimination assay. Response was evaluated according
      to RECIST version 1.1. Results: For the CTR1polymorphism, GT was the most common
      genotype (61.5%) followed by GG (34.6%), and TT (3.8%). For the
      ERCC1polymorphism, only 2 genotypes were found, CC and CT at 57.7% and 42.3%,
      respectively. Genetic polymorphismswere not found to be singly associated with
      response. However, when the 2 genetic polymorphisms were combined,GG/CC showed a
      higher response rate than the others (p=0.018, Fisher's Exact Test). Conclusion:
      This is the first studyto show an association between CTR1 and ERCC1
      polymorphisms and response to gemcitabine-platinum in advancedBTC patients. These
      polymorphisms might be used as biomarkers to predict response in such cases in
      the future.

PMID- 28443324
TI  - Understanding the Increase in Disability Insurance Benefit Receipt in the United
      States.

PMID- 28443325
TI  - Localized Synthesis of Conductive Copper-Tetracyanoquinodimethane Nanostructures
      in Ultrasmall Microchambers for Nanoelectronics.
AB  - In this work, the microfluidic-assisted synthesis of copper
      tetracyanoquinodimethane (Cu-TCNQ) nanostructures in an ambient environment is
      reported for the first time. A two-layer microfluidic device comprising parallel
      actuated microchambers was used for the synthesis and enabled excellent fluid
      handling for the continuous and multiple chemical reactions in confined
      ultrasmall chambers. Different precautions were applied to ensure the reduction
      state of copper (Cu) for the synthesis of Cu-TCNQ charge-transfer compounds. The
      localized synthesis of Cu and in situ transformation to Cu-TCNQ complexes in
      solution were achieved by applying different gas pressures in the control layer.
      Additionally, various diameters of the Cu-TCNQ nano/microstructures were obtained
      by adjusting the concentration of the precursors and reaction time. After the
      synthesis, platinum (Pt) microelectrode arrays, which were aligned at the
      microchambers, could enable the in situ measurements of the electronic properties
      of the synthesized nanostructures without further manipulation. The as-prepared
      Cu-TCNQ wire bundles showed good conductivity and a reversible hysteretic
      switching effect, which proved the possibility in using them to build advanced
      nanoelectronics.

PMID- 28443326
TI  - Ionic Liquid-Silica Precursors via Solvent-Free Sol-Gel Process and Their
      Application in Epoxy-Amine Network: A Theoretical/Experimental Study.
AB  - This work describes the solvent-free sol-gel synthesis of epoxy-functionalized
      silica-based precursors in the presence of 1-butyl-3-methylimidazolium-based
      ionic liquids (ILs) containing different anions: chloride (Cl-) and
      methanesulfonate (MeSO3-). The IL-driven sol-gel mechanisms were investigated in
      detail using experimental characterizations (29Si NMR and ATR FTIR spectroscopy)
      and a theoretical computational method based on density functional theory (DFT).
      We observed complex IL influence on both hydrolysis and condensation steps,
      involving especially H-bonding and Coulomb coupling stabilization of the process
      intermediates. The obtained IL-silica precursors and their further xerogels were
      widely characterized (rheology measurements, MALDI TOF, 29Si NMR, ATR FTIR, and
      DFT simulation), which allowed observation of their precise silica structures and
      established their most energetically favorable conformations. The detected silica
      structures were dependent on the IL type and varied from highly condensed 3D cage
      like to branched ladder-like and cyclic ones. The application of prepared IL
      silica precursors as reinforcing additives into the epoxy-amine network led to an
      improvement in the organic/inorganic interphase interactions through chemical and
      physical bonding. Uniform and well-dispersed silica aggregates, in the size of
      ~30 nm, were formed when <=6.8 wt % of each IL-silica precursor was applied into
      the epoxy-amine network. The use of imidazolium-based ILs contributed to a
      significant improvement in thermomechanical properties of hybrids and reduced
      their UV absorption ability compared to that of the reference matrix. All hybrids
      exhibited an increase in energy to break (up to ~53%), elongation at break (up to
      ~43%), shear storage modulus in the rubbery region (up to 4 times), and thermo
      oxidative stability.

PMID- 28443327
TI  - Acidity-Triggered Tumor Retention/Internalization of Chimeric Peptide for
      Enhanced Photodynamic Therapy and Real-Time Monitoring of Therapeutic Effects.
AB  - Photodynamic therapy (PDT) holds great promise in tumor treatment. Nevertheless,
      it remains highly desirable to develop easy-to-fabricated PDT systems with
      improved tumor accumulation/internalization and timely therapeutic feedback.
      Here, we report a tumor-acidity-responsive chimeric peptide for enhanced PDT and
      noninvasive real-time apoptosis imaging. Both in vitro and in vivo studies
      revealed that a tumor mildly acidic microenvironment could trigger rapid
      protonation of carboxylate anions in chimeric peptide, which led to increased
      zeta potential, improved hydrophobicity, controlled size enlargement, and precise
      morphology switching from sphere to spherocylinder shape of the chimeric peptide.
      All of these factors realized superfast accumulation and prolonged retention in
      the tumor region, selective cellular internalization, and enhanced PDT against
      the tumor. Meanwhile, this chimeric peptide could further generate reactive
      oxygen species and initiate cell apoptosis during PDT. The subsequent formation
      of caspase-3 enzyme hydrolyzed the chimeric peptide, achieving a high
      signal/noise ratio and timely fluorescence feedback. Importantly, direct
      utilization of the acidity responsiveness of a biofunctional Asp-Glu-Val-Asp-Gly
      (DEVDG, caspase-3 enzyme substrate) peptide sequence dramatically simplified the
      preparation and increased the performance of the chimeric peptide furthest.

PMID- 28443328
TI  - Correction to l-Rhamnose Enhances the Immunogenicity of Melanoma-Associated
      Antigen A3for Stimulating Antitumor Immune Responses.

PMID- 28443330
TI  - Mechanisms by Which Salt Concentration Moderates the Dynamics of Human Serum
      Transferrin.
AB  - The dynamical and thermodynamic behavior of human transferrin (hTf) protein in
      saline aqueous solution of various concentrations is studied. hTf is an essential
      transport protein circulating iron in the blood and delivering it to tissues. It
      displays highly pH dependent cooperativity between the two lobes, each carrying
      an iron, and forms a tight complex with the receptor during endocytosis,
      eventually recycled to the serum after iron release. Molecular dynamics
      simulations are used to investigate the effects of the amount of salt on protein
      conformation and dynamics to analyze the structure-function relationship in free
      hTf at serum pH. To monitor the ionic strength dependence, four different ionic
      concentrations, 0, 50, 130, and 210 mM NaCl for two protonation states of the
      iron coordination site is considered. Two mechanisms by which salt affects hTf
      are disclosed. In the totally closed state where iron coordinating tyrosines are
      deprotonated, the addition of even 50 mM of salt alters the electrostatic
      potential distribution around the protein, opening energetic pathways for
      tyrosine protonation from nearby charged residues as a required first step for
      iron release. Once domain opening is observed, conformational plasticity renders
      the iron binding site more accessible by the solvent. At this second stage of
      iron release, R124 in the N-lobe is identified as kinetically significant anion
      binding site that accommodates chloride ions and allosterically communicates with
      the iron binding residues. Opening motions are maximized at 150 mM IS in the N
      lobe, and at 210 mM in the C-lobe. The extra mobility in the latter is thought to
      preclude binding of hTf to its receptor. Thus, the physiological IS is optimal
      for exposing iron for release from hTf. However, the calculated binding
      affinities of iron show that even in the most open conformations, iron
      dissociation needs to be accompanied by chelators.

PMID- 28443329
TI  - Direct Hyperpolarization of Nitrogen-15 in Aqueous Media with Parahydrogen in
      Reversible Exchange.
AB  - Signal amplification by reversible exchange (SABRE) is an inexpensive, fast, and
      even continuous hyperpolarization technique that uses para-hydrogen as
      hyperpolarization source. However, current SABRE faces a number of stumbling
      blocks for translation to biochemical and clinical settings. Difficulties include
      inefficient polarization in water, relatively short-lived 1H-polarization, and
      relatively limited substrate scope. Here we use a water-soluble polarization
      transfer catalyst to hyperpolarize nitrogen-15 in a variety of molecules with
      SABRE-SHEATH (SABRE in shield enables alignment transfer to heteronuclei). This
      strategy works in pure H2O or D2O solutions, on substrates that could not be
      hyperpolarized in traditional 1H-SABRE experiments, and we record 15N T1
      relaxation times of up to 2 min.

PMID- 28443331
TI  - Coupling between the Dynamics of Water and Surfactants in Lyotropic Liquid
      Crystals.
AB  - Bilayers composed of lipid or surfactant molecules are central to biological
      membranes and lamellar lyotropic liquid crystalline (LLC) phases. Common to these
      systems are phases that exhibit either ordered or disordered packing of the
      hydrophobic tails. In this work, we study the impact of surfactant ordering,
      i.e., disordered Lalpha and ordered Lbeta LLC phases, on the dynamics of water
      and sodium ions in the lamellar phases of dicarboxylate gemini surfactants. We
      study the different phases at identical hydration levels by changing the length
      of the hydrophobic tails; surfactants with shorter tails form Lalpha phases and
      those with longer tails form Lbeta phases. We find that the Lalpha phases exhibit
      lower density and greater compressibility than the Lbeta phases, with a hydration
      dependent headgroup surface area. These structural differences significantly
      affect the relative dynamic properties of the phases, primarily the mobility of
      the surfactant molecules tangential to the bilayer surface, as well as the rates
      of water and ion diffusion. We find ~20-50% faster water diffusion in the Lalpha
      phases compared to the Lbeta phases, with the differences most pronounced at low
      hydration. This coupling between water dynamics and surfactant mobility is
      verified using additional simulations in which the surfactant tails are frozen.
      Our study indicates that gemini surfactant LLCs provide an important prototypical
      system for characterizing properties shared with more complex biological lipid
      membranes.

PMID- 28443332
TI  - Copper-Catalyzed Selective Diphenylation of Carboxylic Acids with Cyclic
      Diaryliodonium Salts.
AB  - Herein, we describe a novel one-step copper-catalyzed diphenylation of readily
      available aliphatic or (hetero)aromatic carboxylic acids with cyclic hypervalent
      diaryliodonium reagents. The selective diphenylation of benzoic acids with high
      atom economy can be achieved without observation of the arylation at the phenyl
      hydroxyl/thio/amino position. The valuable biphenyl esters with an additional
      iodo-substituent were obtained in good to excellent yields, which can be further
      transformed to diversified building blocks for the synthesis of bioactive natural
      products, pharmaceuticals, and functional materials. A wide range of different
      functional groups are compatible under the optimized reaction conditions.

PMID- 28443333
TI  - Emulation and Sensitivity Analysis of the Community Multiscale Air Quality Model
      for a UK Ozone Pollution Episode.
AB  - Gaussian process emulation techniques have been used with the Community
      Multiscale Air Quality model, simulating the effects of input uncertainties on
      ozone and NO2 output, to allow robust global sensitivity analysis (SA). A
      screening process ranked the effect of perturbations in 223 inputs, isolating the
      30 most influential from emissions, boundary conditions (BCs), and reaction
      rates. Community Multiscale Air Quality (CMAQ) simulations of a July 2006 ozone
      pollution episode in the UK were made with input values for these variables plus
      ozone dry deposition velocity chosen according to a 576 point Latin hypercube
      design. Emulators trained on the output of these runs were used in variance-based
      SA of the model output to input uncertainties. Performing these analyses for
      every hour of a 21 day period spanning the episode and several days on either
      side allowed the results to be presented as a time series of sensitivity
      coefficients, showing how the influence of different input uncertainties changed
      during the episode. This is one of the most complex models to which these methods
      have been applied, and here, they reveal detailed spatiotemporal patterns of
      model sensitivities, with NO and isoprene emissions, NO2 photolysis, ozone BCs,
      and deposition velocity being among the most influential input uncertainties.

PMID- 28443335
TI  - Selective Complexation of Cyanide and Fluoride Ions with Ammonium Boranes: A
      Theoretical Study on Sensing Mechanism Involving Intramolecular Charge Transfer
      and Configurational Changes.
AB  - The anion binding selectivity and the recognition mechanism of two isomeric
      boranes, namely, 4-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N-trimethylaniline ([p
      (Mes2B)C6H4(NMe3)]+, 1, where "Mes" represents mesitylene and "Me" represents
      methyl) and 2-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N-trimethylaniline ([o
      (Mes2B)C6H4(NMe3)]+, 2) has been investigated using density functional theory
      (DFT) and time dependent-density functional theory (TD-DFT) methods. Natural
      population analysis indicates that the central boron atoms in 1 and 2 are the
      most active centers for nucleophilic addition of anions. The negative magnitude
      of free energy changes (DeltaG) reveals that out of CN-, F-, Cl-, Br-, NO3-, and
      HSO4- only the binding of CN- and F- with 1 and 2 is thermodynamically feasible
      and spontaneous. In addition, the calculated binding energies reveal that the CN-
      is showing lesser binding affinity than F- both with 1 and 2, while other ions,
      viz. NO3-, HSO4-, Br-, and Cl-, either do not bind at all or show very
      insignificant binding energy. The first excited states (S1) of 1 and 2 are shown
      to be the local excited states with pi -> sigma* transition by frontier molecular
      orbital analysis, whereas fourth excited states (S4) of 4-[bis(2,4,6
      trimethylphenyl)boranyl]-N,N,N-trimethylaniline cyanide ([p-(Mes2B)C6H4(NMe3)]
      CN, 1CN, the cyano form of 1) and 4-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N
      trimethylaniline fluoride ([p-(Mes2B)C6H4(NMe3)] F, 1F, the fluoro form of 1) and
      fifth excited state (S5) of 2-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N
      trimethylaniline fluoride ([o-(Mes2B)C6H4(NMe3)] F, 2F, the fluoro form of 2) are
      charge separation states that are found to be responsible for the intramolecular
      charge transfer (ICT) process. The synergistic effect of ICT and partial
      configuration changes induce fluorescence quenching in 1CN, 1F, and 2F after a
      significant internal conversion (IC) from S4 and S5 to S1.

PMID- 28443334
TI  - The N-Terminal Flanking Region Modulates the Actin Binding Affinity of the
      Utrophin Tandem Calponin-Homology Domain.
AB  - Despite sharing a high degree of sequence similarity, the tandem calponin
      homology (CH) domain of utrophin binds to actin 30 times stronger than that of
      dystrophin. We have previously shown that this difference in actin binding
      affinity could not be ascribed to the differences in inter-CH-domain linkers
      [Bandi, S., et al. (2015) Biochemistry 54, 5480-5488]. Here, we examined the role
      of the N-terminal flanking region. The utrophin tandem CH domain contains a 27
      residue flanking region before its CH1 domain. We examined its effect by
      comparing the structure and function of full-length utrophin tandem CH domain
      Utr(1-261) and its truncated Utr(28-261) construct. Both full-length and
      truncated constructs are monomers in solution, with no significant differences in
      their secondary or tertiary structures. Truncated construct Utr(28-261) binds to
      actin 30 times weaker than that of the full-length Utr(1-261), similar to that of
      the dystrophin tandem CH domain with a much shorter flanking region. Deletion of
      the N-terminal flanking region stabilizes the CH1 domain. The magnitude of the
      change in binding free energy upon truncation is similar to that of the change in
      thermodynamic stability. The isolated N-terminal peptide by itself is
      significantly random coil and does not bind to F-actin in the affinity range of
      Utr(1-261) and Utr(28-261). These results indicate that the N-terminal flanking
      region significantly affects the actin binding affinity of tandem CH domains.
      This observation further stresses that protein regions other than the three actin
      binding surfaces identified earlier, irrespective of whether they directly bind
      to actin, also contribute to the actin binding affinity of tandem CH domains.

PMID- 28443336
TI  - MoP/Mo2C@C: A New Combination of Electrocatalysts for Highly Efficient Hydrogen
      Evolution over the Entire pH Range.
AB  - During the exploration of highly efficient noble-metal-free electrocatalysts for
      the hydrogen evolution reaction (HER), a promising and challenging strategy is to
      fabricate composite nanocatalysts by finely tuning metal and/or nonmetal element
      components. Herein, we report a new HER electrocatalyst, which is composed of
      molybdenum phosphide and molybdenum carbide composite nanoparticles (NPs) coated
      by few-layer N-doped graphitic carbon shells (denoted as MoP/Mo2C@C). Such a new
      combination mode of electrocatalysts is realized by a one-step annealing route
      with the mixture of a Mo/P-based polyoxometalate (POM) and dicyandiamide. On the
      basis of this method, the simultaneous phosphorization and carbonization in a
      nanoscale confined space can be easily achieved by the use of POM as the
      molecular-element-regulating platform. MoP/Mo2C@C exhibits more remarkable HER
      performance over the whole pH range than those of MoP, Mo2C, and the physical
      mixture of MoP and Mo2C. The low overpotentials of 89, 136, and 75 mV were
      obtained at a current density of 10 mA cm-2 in the media of pH = 0, 7, and 14,
      respectively. Furthermore, MoP/Mo2C@C shows a long-term durability for 14 h over
      the entire pH range (0-14). Because of the protection of carbon shells, such
      composite electrocatalyst also possesses better transition-metal tolerance
      exemplified by Fe2+, Co2+, and Ni2+ than that of 20% commercial Pt/C. This work
      demonstrates the advantage of POM precursors in adjusting the component and
      properties of nanoscale composite electrocatalysts for HER, which may suggest new
      options for the fabrication of highly efficient composite electrocatalysts.

PMID- 28443337
TI  - Inhaled Nanoparticles Accumulate at Sites of Vascular Disease.
AB  - The development of engineered nanomaterials is growing exponentially, despite
      concerns over their potential similarities to environmental nanoparticles that
      are associated with significant cardiorespiratory morbidity and mortality. The
      mechanisms through which inhalation of nanoparticles could trigger acute
      cardiovascular events are emerging, but a fundamental unanswered question
      remains: Do inhaled nanoparticles translocate from the lung in man and directly
      contribute to the pathogenesis of cardiovascular disease? In complementary
      clinical and experimental studies, we used gold nanoparticles to evaluate
      particle translocation, permitting detection by high-resolution inductively
      coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed
      to nanoparticles by acute inhalation, followed by repeated sampling of blood and
      urine. Gold was detected in the blood and urine within 15 min to 24 h after
      exposure, and was still present 3 months after exposure. Levels were greater
      following inhalation of 5 nm (primary diameter) particles compared to 30 nm
      particles. Studies in mice demonstrated the accumulation in the blood and liver
      following pulmonary exposure to a broader size range of gold nanoparticles (2-200
      nm primary diameter), with translocation markedly greater for particles <10 nm
      diameter. Gold nanoparticles preferentially accumulated in inflammation-rich
      vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore,
      following inhalation, gold particles could be detected in surgical specimens of
      carotid artery disease from patients at risk of stroke. Translocation of inhaled
      nanoparticles into the systemic circulation and accumulation at sites of vascular
      inflammation provides a direct mechanism that can explain the link between
      environmental nanoparticles and cardiovascular disease and has major implications
      for risk management in the use of engineered nanomaterials.

PMID- 28443339
TI  - Gun Marksmanship and Youth Lead Exposure: A Practice-Oriented Approach to
      Prevention.

PMID- 28443338
TI  - Child Passenger Safety Technician Consultation in the Pediatric Primary Care
      Setting.
AB  - Correct use of a child safety seat (CSS) can reduce the risk of fatal motor
      vehicle crash-related injury by up to 71%; however, misuse rates for CSS are as
      high as 70%. We recruited 189 caregivers at 2 large suburban pediatric office
      practices; 94 in the intervention group and 95 in the control group. All
      participants completed a baseline survey and received a CSS safety brochure.
      Intervention participants had their CSS installation checked at enrollment by a
      certified child passenger safety (CPS) technician. Follow-up was conducted 4
      months post enrollment. Intervention group participants had a 21.3% reduction in
      critical misuse at follow-up, whereas control participants critical misuse rate
      at follow-up was identical to the intervention group at baseline. A consult with
      a certified CPS technician, at the time of a routine visit to the pediatrician,
      resulted in a reduction in CSS misuse rates.

PMID- 28443341
TI  - Erratum.

PMID- 28443340
TI  - E-cigs . . . Are They Cool? Talking to Teens About E-Cigarettes.
AB  - Electronic cigarettes, or e-cigarettes as they are commonly called, have gained
      wide acceptance among adolescents, especially those with sweet flavors such as
      bubble gum and cheesecake. Although health effects of e-cigarettes have not been
      well characterized, their use increases a teen's exposure to nicotine and may
      serve as a gateway to traditional cigarettes. This article outlines the basics of
      e-cigarettes and potential health hazards, followed by selected literature on
      teens' perceptions of e-cigarettes, as well as motivational interviewing
      strategies that can be used in talking to teens about using electronic
      cigarettes.

PMID- 28443342
TI  - Catalyzing Implementation of Evidence-Based Interventions in Safety Net Settings:
      A Clinical-Community Partnership in South Los Angeles.
AB  - This study is a process evaluation of a clinical-community partnership that
      implemented evidence-based interventions in clinical safety net settings.
      Adoption and implementation of evidence-based interventions in these settings can
      help reduce health disparities by improving the quality of clinical preventive
      services in health care settings with underserved populations. A clinical
      community partnership model is a possible avenue to catalyze adoption and
      implementation of interventions amid organizational barriers to change. Three
      Federally Qualified Health Centers in South Los Angeles participated in a
      partnership led by a local community-based organization (CBO) to implement
      hypertension interventions. Qualitative research methods were used to evaluate
      intervention selection and implementation processes between January 2014 and June
      2015. Data collection tools included a key participant interview guide, health
      care provider interview guide, and protocol for taking meeting minutes. This case
      study demonstrates how a CBO acted as an external facilitator and employed a
      collaborative partnership model to catalyze implementation of evidence-based
      interventions in safety net settings. The study phases observed included
      initiation, planning, and implementation. Three emergent categories of
      organizational facilitators and barriers were identified (personnel capacity,
      professional development capacity, and technological capacity). Key participants
      and health care providers expressed a high level of satisfaction with the
      collaborative and the interventions, respectively. The CBO's role as a
      facilitator and catalyst is a replicable model to promote intervention adoption
      and implementation in safety net settings. Key lessons learned are provided for
      researchers and practitioners interested in partnering with Federally Qualified
      Health Centers to implement health promotion interventions.

PMID- 28443343
TI  - Impact on Diabetes Self-Management and Glycemic Control of a New Color-Based SMBG
      Meter.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG) is a key pillar of personal
      diabetes management. The objective of this observational study was to analyze
      diabetes self-management (DSM) and glycemic outcomes before and during system
      implementation in real-life settings of a blood glucose meter system with a color
      coded display of glucose levels, which helps identify out-of-range levels.
      METHODS: A total of 193 insulin-treated diabetes patients (11% T1DM; 55% male,
      age 60 +/- 4 years, mean diabetes duration 14 +/- 9 years, HbA1c 8.68 +/- 1.2%)
      were enrolled into the study. Both the Diabetes Self-Management Questionnaire
      (DSMQ) and glycemic control were analyzed at baseline and 3 and 6 months after
      study initiation. RESULTS: DSMQ general perception improved significantly by the
      end of the study period ("Sum Scale," P < .05). Moreover, after 6 months
      patient's attitudes on self-care (Q16, P = .0046) and nutrition ("Dietary
      Control," P = .004) showed significant improvements. Use of the blood glucose
      meter resulted in improved glycemic control, as shown by mean HbA1c levels, which
      decreased from 8.68 +/- 1.2% at baseline to 8.13 +/- 1.02% after 3 months ( P <
      .0001) and to 7.9 +/- 1.1% at 6 months ( P < .0001). Both patients and diabetes
      educators agreed in the advantages of the color-coded indicator and on its
      helpfulness in assisting patients on their diabetes management, as drawn from the
      results of the self-reported satisfaction questionnaire. CONCLUSION: This real
      world study demonstrates that SMBG implemented via this new blood glucose meter
      not only leads to an improvement in metabolic control, but also is associated
      with a significant improvement in diabetes management.

PMID- 28443344
TI  - Strengths and Limitations of New Approaches for Graphical Presentation of Blood
      Glucose Monitoring System Accuracy Data.
AB  - Graphical presentation of blood glucose monitoring systems' (BGMSs) accuracy
      typically includes difference plots (DPs). Recently, 3 new approaches were
      presented: radar plots (RPs), rectangle target plots (RTPs), and surveillance
      error grids (SEGs). BGMS data were modeled based on 3 scenarios that can be
      encountered in real life to highlight strengths and limitations of these
      approaches. Detailed assessment of BGMS data may be easier in plots with
      individual data points (DPs, RPs, SEGs), whereas RTPs may facilitate display of
      large amounts of data or comparison of BGMS. SEGs have the advantage of assessing
      clinical risk. The selection of a specific type depends mostly on the kind of
      information sought (eg, accuracy in specific concentration intervals, lot-to-lot
      variability, clinical risk) as there is no "absolute best" approach.

PMID- 28443347
TI  - RANZCP Abstracts.

PMID- 28443345
TI  - Engaging School Mental Health Professionals to Deliver Evidence-Based
      Interventions to Hispanic Families.
AB  - Research has demonstrated that a number of evidence-based programs can be
      effectively implemented in different community settings, such as schools, to
      target Hispanic youth and their families; however, successful implementation of
      such programs represents a challenge for practitioners. This article describes
      experiences and strategies associated with recruiting, training, and supervising
      school mental health professionals in the school-based implementation of an
      evidence-based, family-centered prevention program for Hispanic families. School
      mental health professionals were recruited and given intensive training, weekly
      supervision for adherence monitoring, and ongoing technical assistance, in
      addition to intervention manuals and materials. We emphasize how strategies based
      on the prevention program itself were used to recruit, engage, and train school
      mental health professionals to deliver a family-based evidence-based program,
      blending research and practice in a large public school system. Implications of
      lessons learned are discussed, as well as the specific strategies to overcome
      challenges when engaging and training community partners in delivering a
      manualized intervention with rigorous adherence to the program.

PMID- 28443349
TI  - Pharmacotherapy for the treatment of tardive dyskinesia in schizophrenia
      patients.
AB  - INTRODUCTION: Tardive dyskinesia (TD) is an iatrogenic movement disorder most
      commonly observed in patients with psychotic disorders who are treated with
      dopamine blocking antipsychotic medications. Treatment options are limited, and
      recommendations for treatment are based on a relative scarcity of evidence. Areas
      covered: After briefly highlighting current mechanistic theories of TD, this
      review will discuss the evidence for a number of medications of several different
      classes that have been studied for the treatment of TD since the 1970s with an
      emphasis on placebo controlled trials when possible. We used a Pubmed search of
      primary studies, reviews, and metaanalyses on the topic of TD treatment in order
      to cover this topic. Expert opinion: Treatment of TD is difficult given limited
      data and incomplete understanding of the mechanism. Treatment of TD must be
      evaluated on an individual basis with careful weight given to severity of
      symptoms. We suggest the use of atypical versus conventional antipsychotics
      whenever possible and would recommend trials with one or more of a number of
      additional agents starting with valbenazine.

PMID- 28443350
TI  - The Validation of a School-Based, Culturally Grounded Drug Prevention Curriculum
      for Rural Hawaiian Youth.
AB  - The purpose of this study was to validate a school-based, culturally grounded
      drug prevention curriculum for rural Native Hawaiian youth. Faculty and
      administrators from eight geographically dispersed middle-, intermediate-, or
      multilevel schools on Hawai'i island were interviewed on the cultural relevance
      and feasibility of implementation of the curriculum (Ho'ouna Pono). While all
      participants appreciated the culturally specific content interwoven throughout
      the curriculum's structure, several of them expressed concerns that the
      curriculum would compete with resources needed to implement Common Core national
      standards. Implications for the implementation, adoption, and sustainability of
      school-based prevention curricula are discussed.

PMID- 28443351
TI  - Current and future chemical therapies for treating anaemia in chronic kidney
      disease.
AB  - INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) are not perfect, since
      they have potential side effects. Iron therapy is also receiving growing
      attention in recent years. Areas covered: We performed a literature search on
      PubMed using the following key words: anemia, chronic kidney disease, HIF
      stabilisers, sotatercept, actin traps, iron, iron-containing phosphate binders,
      iron dialysate. We reviewed new drugs that are under clinical development to
      obtain better safety and activity and/or easier and cheaper manufacturing
      processes in comparison to available ESAs. We also considered new strategies to
      increase iron stores. Several phase 1 and 2 studies support the beneficial role
      of increasing Hypoxia Inducible factor (HIF) activity for stimulating endogenous
      erythropoiesis. Sotatercept and luspatercept, two activin traps, are undergoing
      clinical development mainly for indications other than CKD. They have the
      additional effect of improving osteoporosis. Iron-containing phosphate binders
      have become available recently. Expert opinion: Several medical needs are unmet
      with ESA. HIF stabilisers are the most appealing drugs undergoing clinical
      development. They expose patients to lower levels of EPO than ESA, possibly
      reducing unintended effects. Their long-term safety is still to be demonstrated.
      One new iron-containing phosphate binders has the potential of combining two
      indications: hyperphosphoremia and iron deficiency, possibly improving
      compliance.

PMID- 28443352
TI  - GFF MDI for the improvement of lung function in COPD - A look at the PINNACLE-1
      and PINNACLE-2 data and beyond.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading
      cause of death globally and incidence rates are continuing to rise. Long-acting
      bronchodilators are the foundation on which current pharmacological approaches to
      COPD management are built, with long-acting muscarinic antagonists (LAMAs) and
      long-acting beta2-agonists (LABAs) recommended across the spectrum of the disease
      continuum. Combining LAMAs and LABAs provides additional lung function
      improvements and relief of patient symptoms compared with either therapy alone.
      Several options for LAMA/LABA fixed-dose combinations (FDC) delivered via a
      single inhaler device are available; however, only recently has a LAMA/LABA FDC
      become available as a pressurized metered dose inhaler (MDI). Areas covered: This
      article describes the rationale for the development of the LAMA/LABA FDC of
      glycopyrrolate and formoterol fumarate, formulated by Co-SuspensionTM Delivery
      Technology and delivered by MDI (GFF MDI). The clinical trial program of GFF MDI,
      including the pivotal Phase III studies (PINNACLE-1 and PINNACLE-2) that
      supported regulatory approval, are reviewed, providing insights into
      interpretation and future directions for research. Expert commentary: LAMA/LABA
      FDCs are already a crucial part of the COPD treatment paradigm, but additional
      data are needed in order to maximize their role as maintenance therapies in
      patients with COPD.

PMID- 28443353
TI  - Anticholinergic toxicity associated with ingestion of water containing lupini
      bean extract.

PMID- 28443354
TI  - Optimization of intelligent infusion pump technology to minimize vasopressor pump
      programming errors.
AB  - BACKGROUND: There is a lack of data evaluating the impact of hard limit
      implementation into intelligent infusion pump technology (IIPT). The purpose of
      this study was to determine if incorporation of vasopressor upper hard limits
      (UHL) into IIPT increases efficacy of alerts by preventing pump programming
      errors. METHODS: Retrospective review from five hospitals within a single
      healthcare network between April 1, 2013 and May 31, 2014. A total of 65,680
      vasopressor data entries were evaluated; 19,377 prior to hard limit
      implementation and 46,303 after hard limit implementation. The primary outcome
      was the percent of effective alerts. The secondary outcome was the proportional
      dose increase from the soft limit provided. RESULTS: A reduction in alert rate
      occurred after incorporation of hard limits to the IIPT drug library (pre-UHL
      4.7% vs. post-UHL 4.0%) with a subsequent increase in the number of errors
      prevented as represented by a higher effective alert rate (pre-UHL 23.0% vs. post
      UHL 37.3%; p < 0.001). The proportional dose increase was significantly reduced
      (pre-UHL 188% +/- 380%] vs. post-UHL 95% +/- 128%; p < 0.001). CONCLUSIONS:
      Incorporation of UHLs into IIPT in a multi-site health system with varying
      intensive care unit and emergency department acuity increases alert
      effectiveness, reduces dosing errors, and reduces the magnitude of dosing errors
      that reach the patient.

PMID- 28443355
TI  - Investigational dopamine antagonists for the treatment of schizophrenia.
AB  - INTRODUCTION: Schizophrenia is a debilitating illness with a chronic impact on
      social function and daily living. Although various antipsychotics are available,
      there are still many challenges and unmet needs. Thus, many compounds with
      diverse mechanisms have been investigated, but all approved antipsychotics still
      require interactions with dopamine D2 receptors. Areas covered: We searched for
      investigational drugs using the key words 'dopamine' and 'schizophrenia' in
      American and European clinical trial registers (clinicaltrials.gov;
      clinicaltrialsregister.eu). Published articles were searched in PubMed, Embase,
      Medline, PsycINFO, Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), the Web of Science and the Cochrane Central Register of Controlled
      Trials Library. Expert opinion: The prospect of developing a dopamine antagonist
      is hopeful. Brexpiprazole and cariprazine, which were agents listed as
      'investigational dopamine antagonists,' just received FDA approval. Novel agents
      such as BL 1020, ITI-007, and JNJ-37822681 have solid published data available,
      and agents such as L-THP, Lu AF35700, S33138, and SB-773812 are under vigorous
      investigation. However, the expected benefits of the newly developed antagonists
      may not be great because they offer little enhanced efficacy for negative
      symptoms, cognition and functional outcomes.

PMID- 28443356
TI  - Sham or no sham control: that is the question in trials of renal denervation for
      resistant hypertension. A systematic meta-analysis.
AB  - BACKGROUND: Studies of renal denervation (RDN) in patients with apparent
      treatment resistant hypertension have been hampered by a number of patient and
      physician related confounders on blood pressure (BP) including poor drug
      adherence. It remains uncertain whether RDN lowers BP. We aimed to investigate
      whether the use of sham control is essential in RDN studies or whether systematic
      use of 24-hour ambulatory BP provides enough information thereby making an
      invasive sham control redundant. METHODS: We meta-analyzed randomized controlled
      trials of the BP response to RDN on top of continued or optimized
      antihypertensive drugs in patients with resistant hypertension. On top of the
      randomized trials reviewed earlier, we additionally included three studies, one
      conducted in Spain (24 patients, RDN vs. spironolactone), one conducted in
      Denmark (69 patients, sham controlled) and one conducted in Netherlands (139
      patients, RDN vs. continued treatment). We analyzed 24-hour ambulatory BP in 3
      sham controlled studies vs. 7 no sham controlled studies. RESULTS: The updated
      meta-analysis of 10 studies showed 3.6 mmHg (p = .45) and 1.0 mmHg (p = .54)
      reductions in office and in 24-hour systolic BP, respectively. Meta-analysis of
      24-hour systolic BP in the 3 sham-controlled studies showed a reduction of 2.18
      mmHg (95% confidence intervals (CIs) -4.70 to 0.33 mmHg, n = 396 vs. 230, p =
      .07). For the 7 no sham controlled studies there was no difference in 24-hour
      systolic BP (+0.38 mmHg; 95% CIs -5.29 to 6.04 mmHg, n = 215 vs. 245, p = .90).
      The test for sub-group heterogeneity showed no significant interaction (p = .69).
      Removing one trial at a time produced confirmatory results. CONCLUSION: The
      overall meta-analysis of 10 randomized and controlled studies showed no
      significant effect on BP of RDN in resistant hypertension. Moreover, our analysis
      does not support the use of sham control but rather suggests extensive use of 24
      hour ambulatory BP in studies of RDN in resistant hypertension.

PMID- 28443357
TI  - Informed consent and the aftermath of cardiopulmonary resuscitation: Ethical
      considerations.
AB  - BACKGROUND: Patients often are confronted with the choice to allow
      cardiopulmonary resuscitation (CPR) should cardiac arrest occur. Typically,
      informed consent for CPR does not also include detailed discussion about survival
      rates, possible consequences of survival, and/or potential impacts on
      functionality post-CPR. OBJECTIVE: A lack of communication about these issues
      between providers and patients/families complicates CPR decision-making and
      highlights the ethical imperative of practice changes that educate patients and
      families in those deeper and more detailed ways. DESIGN: This review integrates
      disparate literature on the aftermath of CPR and the ethics implications of CPR
      decision-making as it relates to and is affected by informed consent and
      subsequent choices for code status by seriously ill patients and their
      surrogates/proxies within the hospital setting. Margaret Urban Walker's moral
      philosophy provides a framework to view informed consent as a practice of
      responsibility. Ethical considerations: Given nurses' communicative skills, ethos
      of care and advocacy, and expertise in therapeutic relationships, communication
      around DNAR decision-making might look quite different if institutional norms in
      education, healthcare, law, and public policy held nurses overtly responsible for
      informed consent in some greater measure. FINDINGS: Analysis from this
      perspective shows where changes in informed consent practices are needed and
      where leverage might be exerted to create change in the direction of deeper and
      more detailed discussions about CPR survival rates and possible consequences of
      survival.

PMID- 28443358
TI  - Cerebral rituximab uptake in multiple sclerosis: A 89Zr-immunoPET pilot study.
AB  - Previous studies have demonstrated that the chimeric monoclonal antibody
      rituximab significantly reduces clinical and radiological disease activity in
      relapsing-remitting multiple sclerosis as early as 4 weeks after the first
      administration. The exact mechanisms leading to this rapid effect have not yet
      been clarified. The aim of this positron emission tomography study was to assess
      central nervous system penetration as a possible explanation, using zirconium-89
      labelled rituximab. No evidence was found for cerebral penetration of
      [89Zr]rituximab.

PMID- 28443359
TI  - Targeting LRRK2 in Parkinson's disease: an update on recent developments.
AB  - INTRODUCTION: LRRK2 research has progressed significantly in recent years with
      more reports of LRRK2 interactors and the development of more specific and
      sophisticated LRRK2 kinase inhibitors. Identification of bone fide LRRK2
      substrates will provide new therapeutic targets in LRRK2-linked Parkinson's
      disease (PD). Areas covered: This review aims to put current LRRK2 research into
      perspective. Beginning with recent LRRK2 mammalian models employed for in vivo
      validation of LRRK2 substrates, followed by updates on reported LRRK2 interactors
      and their inferred mechanisms. Finally an overview of commonly used LRRK2 kinase
      inhibitors will be depicted. Expert opinion: Identification of LRRK2 non-kinase
      functions suggests the possibility of alternative LRRK2 drug target sites and
      these should be further explored. Studies on the effects of LRRK2 kinase
      inhibition on its non-kinase function and its self-regulatory role will provide
      further insights on its pathophysiologic mechanisms. Development of robust
      measurements of LRRK2 inhibitor efficacy will be required. These would include
      identification of specific imaging ligands or direct biochemical assays that can
      accurately capture its intrinsic activity. Testing of new therapeutic drug
      targets in both LRRK2 carriers and non LRRK2-linked patients will be important
      since their phenotype is similar.

PMID- 28443360
TI  - Overview of procalcitonin assays and procalcitonin-guided protocols for the
      management of patients with infections and sepsis.
AB  - INTRODUCTION: Procalcitonin is a surrogate infection blood marker whose levels
      help estimate the likelihood of bacterial infections and correlate with their
      resolution. Recent trials have revealed the benefits of inclusion of
      procalcitonin in antibiotic stewardship protocols for initiation and
      discontinuation of antimicrobial therapy. Areas covered: Procalcitonin-guided
      antibiotic stewardship protocols have shown appreciable reductions in antibiotic
      use and duration of therapy in respiratory infections, sepsis, and other
      infections, with positive effects on clinical outcomes. Multiple fully automated
      and sensitive procalcitonin assays are routinely used in clinical practice.
      Utilization of these assays requires consideration of the clinical setting and
      knowledge of assay characteristics, particularly assay sensitivities,
      reproducibility, and performance across routinely used cut-off ranges. The
      authors provide an overview of the strengths and limitations of currently
      available procalcitonin assays and antibiotic therapy algorithms incorporating
      procalcitonin currently used in different clinical settings and in patients with
      different underlying infections. Expert commentary: Use of sensitive
      procalcitonin measurements in clinical algorithms can reduce antimicrobial
      overuse, decreasing the risk of side effects and controlling emerging bacterial
      multi-resistance. Before use in clinical practice, it is important to carefully
      assess the quality of novel PCT assays and rigorously evaluate them in target
      patient populations across clinically relevant cut-off ranges.

PMID- 28443361
TI  - The effect of alkali on the product distribution from black liquor conversion
      under supercritical water.
AB  - Lignin in chemical pulping waste, or black liquor (BL), can be converted into
      various products via supercritical water gasification (SCWG). However, the
      inherited alkaline contents from the pulping chemicals may affect the product
      yields and properties. In this research, the influence of the residual alkali on
      the product distribution via SCWG of soda BL and kraft BL was evaluated. The SCWG
      was performed in a batch quartz reactor for 10 min at various temperatures (673,
      773 and 873 K) and pressures (250, 300 and 400 bar). The highest hydrogen (H2)
      production occurred at 873 K for the soda BL. The water-gas shift reaction with
      sodium ions played an important part in the H2 production, while only small
      amounts of methane and carbon monoxide were detected. Hydrocarbons, carboxylic
      acids and esters were the dominant substrates in the liquid products, which
      denoted the potential of this method for bond cleaving of the lignin
      macromolecule. As a result, BL, which typically contains alkali salt, was an
      appropriate feedstock for the SCWG reaction to produce renewable fuel. This
      method not only has a positive influence on the generation of value added
      products from highly corrosive waste but also helps avoid some technical problems
      commonly encountered with direct firing in a recovery boiler.

PMID- 28443362
TI  - Effect of the side chain spacer structure on the pH-responsive properties of
      polycarboxylates.
AB  - The properties of stimuli-responsive polymers change significantly with changes
      to their environment, such as temperature and pH. This behavior can be utilized
      for the preparation of stimuli-responsive carriers for efficient cytosolic
      delivery of active drugs. Among the possible environmental conditions, pH is one
      of the most useful stimuli because the pH in an endosome is lower than under
      physiological conditions, depending on endosomal development. This pH difference
      is an important factor in the design of pH-responsive polymers, which can be used
      to enhance the transport of endocytosed drugs from the endosomal compartment to
      the cytoplasm. Such polymers can destabilize the endosomal bilayer under mildly
      acidic conditions and be nondisruptive at pH 7.4 not only for efficient endosomal
      escape but also for the suppression of nonspecific interaction with lipids
      existing under physiological conditions. In this study, we developed
      polycarboxylates with well-controlled pH-responsive properties bearing various
      spacer structures with different hydrophobicity. 3-methyl glutarylated
      polyallylamine and 2-carboxy-cyclohexanoylated polyallylamine were synthesized
      through the reaction between primary amine of PAA and acid anhydrides. Side chain
      spacers with higher hydrophobicity induced significant interactions with
      liposomal membranes at higher pH. pH-destabilizing liposomes could be modulated
      through the changing the composition of spacer structures with different
      hydrophobicity. Such formulations may represent an attractive strategy for the
      improvement of cytosolic delivery of active molecules.

PMID- 28443363
TI  - A mathematical model of aerobic methane oxidation coupled to denitrification.
AB  - Aerobic methanotrophic bacteria use methane as their only source of energy and
      carbon. They release organic compounds that can serve as electron donors for co
      existing denitrifiers. This interaction between methanotrophs and denitrifiers is
      known to contribute to nitrogen losses in natural environments and has also been
      exploited by researchers for denitrification of nitrate-contaminated wastewater.
      The purpose of this study was to develop a mathematical model describing aerobic
      methane oxidation coupled to denitrification in suspended-growth reactors. The
      model considered the activities of three microbial groups: aerobic methanotrophs,
      facultative methylotrophs, and facultative heterotrophs. The model was tested
      against data from the scientific literature and used to explore the effects of
      the oxygen mass transfer coefficient, the solids retention time, and the fraction
      methane in the feed gas on nitrate removal. The fraction of methane in the feed
      gas was found to be critical for the nitrate removal rate. A value of about 15%
      in air was optimal. A lower methane fraction led to excess oxygen, which was
      detrimental for denitrification. A higher fraction led to oxygen-limitation,
      which restricted the growth rate of methanotrophs in the reactor.

PMID- 28443364
TI  - Green synthesis of nano-zero-valent iron from Nettle and Thyme leaf extracts and
      their application for the removal of cephalexin antibiotic from aqueous
      solutions.
AB  - In this study, the removal of cephalexin (CEX) antibiotic from aqueous solution
      was examined using a novel green adsorbent without employing any toxic chemicals
      or capping agents. Nettle and Thyme extracts were used to synthesize novel nano
      zero-valent iron (NNZVI and TNZVI) for the adsorption of CEX. The nature and
      morphology of synthesized adsorbent were characterized by Transmission electron
      microscopy, scanning electron microscope, X-ray diffraction and Fourier transform
      infrared spectroscopy spectroscopy. Batch experiments were performed to study the
      influence of various experimental parameters such as contact time, initial
      concentration of the CEX, solution pH and adsorbent dosage. The adsorption
      isotherms of CEX by NNZVI and TNZVI were found to fit well with Freundlich and
      Langmuir models, respectively. The maximum adsorption capacity of CEX onto NNZVI
      and TNZVI were observed as 1667 and 1428 mg/g, respectively, based on the
      Langmuir model. The adsorption trend followed the pseudo-first-order kinetics
      model and equilibrium could be established in about two hours for both
      adsorbents. The developed nanoparticles in this study have considerable potential
      for the removal of CEX and could be considered as a promising adsorbent for the
      removal of other antibiotics also from aqueous solutions.

PMID- 28443365
TI  - Enhanced phosphorus reduction in simulated eutrophic water: a comparative study
      of submerged macrophytes, sediment microbial fuel cells, and their combination.
AB  - The phosphorus reduction in water column was attempted by integrating sediment
      microbial fuel cells (SMFCs) with the submerged macrophyte Vallisneria spiralis.
      A comparative study was conducted to treat simulated water rich in phosphate with
      a control and three treatments: SMFC alone (SMFC), submerged macrophytes alone
      (macophyte), and combined macrophytes and fuel cells (M-SMFC). All treatments
      promoted phosphorus flux from the water column to sediments. Maximum phosphorus
      reduction was obtained in proportion to the highest stable phosphorus level in
      sediments in M-SMFC. For the initial phosphate concentrations of 0.2, 1, 2, and 4
      mg/L, average phosphate values in the overlying water during four phases
      decreased by 33.3% (25.0%, 8.3%), 30.8% (5.1%, 17.9%), 36.5% (27.8%, 15.7%), and
      36.2% (0.7%, 22.1%) for M-SMFC (macrophyte, SMFC), compared with the control.
      With macrophyte treatment, the obvious phosphorus release from sediments was
      observed during the declining period. However, such phenomenon was significantly
      inhibited with M-SMFC. The electrogenesis bacteria achieved stronger phosphorus
      adsorption and assimilation was significantly enriched on the closed-circuit
      anodes. The higher abundance of Geobacter and Pseudomonas in M-SMFC might in part
      explain the highest phosphorus reduction in the water column. M-SMFC treatment
      could be promising to control the phosphorus in eutrophic water bodies.

PMID- 28443366
TI  - Self-stigma, insight, and family burden among Israeli mothers of people with
      serious mental illness: Ethno-national considerations.
AB  - The current cross-sectional study investigated and compared the associations
      between insight, self-stigma, and family burden among Jewish and Arab mothers of
      an adult son or daughter with serious mental illness (SMI) in Israel. A total of
      162 Israeli mothers of a person with SMI participated in the study; 95 were
      Jewish (58.6%), and 67 were Arab (41.4%). Insight, self-stigma, and family burden
      scales were administered. Jewish mothers reported higher levels of insight into
      their son's or daughter's illness and reported greater family burden compared to
      Arab mothers. No significant differences in self-stigma scores were found between
      Jewish and Arab mothers. The pattern of associations between insight, self
      stigma, and burden differed between Jewish and Arab mothers. Self-stigma was
      found to mediate the relationship between insight and burden among Jewish mothers
      but not among Arab mothers. Ethno-national affiliation should be taken into
      consideration regarding how family members conceptualize and experience mental
      illness, as this might affect care.

PMID- 28443367
TI  - Preventing risky behaviours among young adolescents in eastern Democratic
      Republic of Congo: A qualitative study.
AB  - This qualitative study explores and describes adolescent risk behaviours,
      specifically consumption of alcohol and use of violence; the perceived
      consequences of these behaviours on future well-being and relationships; and
      collaboratively identifies the essential components of a prevention intervention
      for risk behaviours (alcohol use, violence) among young adolescents while
      strengthening the protective individual and relationship factors in post-conflict
      Democratic Republic of Congo. One-on-one in-depth interviews were conducted with
      28 male and female youth, 20 parents/guardians and 20 stakeholders in three rural
      villages of South Kivu Province. Trained interviewers conducted interviews and
      participated in daily debriefing. Descriptive qualitative analysis was used to
      analyse the data. Youth use of violence and alcohol was associated with a range
      of factors including peer influence, parent behaviours, school enrolment and
      poverty. The consequences of risk behaviour include damaged family and social
      bonds, reduced economic and educational productivity and promise. Community
      based, multilevel prevention interventions that promote protective factors and
      reduce youth exposure and vulnerability to risk factors may have immediate and
      long-term impact on youth health and behaviour. Such a programme could engage
      youth, adults and local stakeholders in a range of social, educational and
      economic activities.

PMID- 28443368
TI  - Improving bioelectricity generation and COD removal of sewage sludge in microbial
      desalination cell.
AB  - Improving wastewater treatment process and water desalination are two important
      solutions for increasing the available supply of fresh water. Microbial
      desalination cells (MDCs) with common electrolytes display relatively low organic
      matter removal and high cost. In this study, sewage sludge was used as the
      substrate in the Microbial desalination cell (MDC) under three different initial
      salt concentrations (5, 20 and 35 g.L-1) and the maximum salt removal rates of
      50.6%, 64% and 69.6% were obtained under batch condition, respectively. The MDC
      also produced the maximum power density of 47.1 W m-3 and the averaged chemical
      oxygen demand (COD) removal of 58.2 +/- 0.89% when the initial COD was 6610 +/-
      83 mg L-1. Employing treated sludge as catholyte enhanced COD removal and power
      density to 87.3% and 54.4 W m-3, respectively, with counterbalancing pH variation
      in treated effluent. These promising results showed, for the first time, that the
      excess sewage sludge obtained from biological wastewater treatment plants could
      be successfully used as anolyte and catholyte in MDC, achieving organic matter
      biodegradation along with salt removal and energy production. In addition, using
      treated sludge as catholyte will improve the performance of MDC and introduce a
      more effective method for both sludge treatment and desalination.

PMID- 28443369
TI  - Electro activation of persulfate using iron sheet as low-cost electrode: the role
      of the operating conditions.
AB  - This work assesses the role of the operational conditions upon the electro
      activation of persulfate (PS) using sacrificed iron electrode as a continuous low
      cost Fe2+ source. An aqueous phenol solution (100 mg L-1) was selected as model
      effluent. The studied variables include current density (1-10 mA cm-2),
      persulfate concentration (0.7-2.85 g L-1), temperature (30-90 degrees C) and the
      solution conductivity (2.7-20.7 mS cm-1) using Na2SO4 and NaCl as supporting
      electrolyte. A mineralization degree of around 80% with Na2SO4 and 92% in
      presence of NaCl was achieved at 30 degrees C using 2.15 g L-1 PS at the lowest
      current density tested (1 mA cm-2). Besides PS concentration, temperature was the
      main variable affecting the process. In the range of 30-70 degrees C, it showed a
      positive effect, achieving TOC conversion above 95% (using Na2SO4 under the
      previous conditions) along with a significant increase in iron sludge, which
      adversely affects the economy of the process. A lumped and simplified kinetic
      model based on persulfate consumption and TOC mineralization is suggested. The
      activation energy obtained for the TOC decay was 29 kJ mol-1. An estimated
      operating cost of US$ 3.00 per m3 was obtained, demonstrating the economic
      feasibility of this process.

PMID- 28443371
TI  - Solutions to Address Diabetes-Related Financial Burden and Cost-Related
      Nonadherence: Results From a Pilot Study.
AB  - BACKGROUND: Cost-related nonadherence (CRN) to recommended self-management
      behaviors among adults with chronic conditions such as diabetes is prevalent. Few
      behavioral interventions to mitigate CRN have been tested and evaluated. AIMS: We
      developed a financial burden resource tool and examined its acceptability and the
      preliminary effects on patient-centered outcomes among adults with diabetes or
      prediabetes seen in a clinical setting. METHOD: We report a pre-post one-group
      design pilot study. From an endocrinology clinic, we recruited 104 adults with
      diabetes who reported financial burdens with their diabetes management or engaged
      in CRN behaviors. We offered participants the financial burden resource tool we
      developed, which provided tailored, low-cost resource options for diabetes
      management and other social needs. Acceptability and self-reported outcomes were
      assessed 2 months after use of the tool. RESULTS: Mean age of participants was
      50.5 years ( SD = 15.3). Participants found the tool highly acceptable across 15
      indicators (e.g., 93% "learned a lot," 98% "topics relevant" 95% "applicable to
      their lives," 98% "liked the information"). Significant improvements between
      baseline and 2-month follow-up were observed for discussion of cost concerns with
      nurses (19% to 29%, p < .05) and pharmacists (13% to 25.5%, p < .01), not
      skipping doses of medicines due to cost (11% to 4%, p < .03), and financial
      management (33.83 to 39.62, p < .007). There were no significant changes in
      perception of financial burden. CONCLUSION: A financial burden resource tool is
      highly acceptable to patients, is easy to administer, and can prompt behavior
      change. This pilot study supports the need for well-powered trials with longer
      follow-up to further evaluate the effectiveness of such tools in improving CRN
      and key outcomes.

PMID- 28443370
TI  - Interrelationships Between Health Behaviors and Coping Strategies Among Informal
      Caregivers of Cancer Survivors.
AB  - BACKGROUND: Recent research among cancer survivors suggests that health behaviors
      and coping are intertwined, with important implications for positive behavior
      change and health. Informal caregivers may have poor health behaviors, and
      caregivers' health behaviors have been linked to those of survivors. AIMS: This
      hypothesis generating study assessed the correlations among health behaviors and
      coping strategies in a population of lung and colorectal cancer caregivers.
      METHOD: This cross-sectional study used data from the Cancer Care Outcomes
      Research & Surveillance Consortium. Caregivers ( n = 1,482) reported their health
      behaviors, coping, and sociodemographic and caregiving characteristics.
      Descriptive statistics assessed the distribution of caregivers' health and coping
      behaviors, and multivariable linear regressions assessed the associations between
      health behaviors and coping styles. RESULTS: Many informal caregivers reported
      regular exercise (47%) and adequate sleep (37%); few reported smoking (19%) or
      binge drinking (7%). Problem-focused coping was associated with greater physical
      activity and less adequate sleep (effect sizes [ESs] up to 0.21, p < .05). Those
      with some physical activity scored higher on emotion-focused coping, while binge
      drinkers scored lower (ES = 0.16 and 0.27, p < .05). Caregivers who reported
      moderate daily activity, current smoking, binge drinking, and feeling less well
      rested scored higher on dysfunctional coping (ES up to 0.49, p < .05).
      DISCUSSION: Health behaviors and coping strategies were interrelated among
      informal cancer caregivers. The relationships suggest avenues for future
      research, including whether targeting both factors concurrently may be
      particularly efficacious at improving informal caregiver self-care. CONCLUSION:
      Understanding the link between health behaviors and coping strategies may inform
      health behavior research and practice.

PMID- 28443372
TI  - Cord blood as a potential therapeutic for amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative
      disease characterized by progressive motor neuron degeneration in the brain and
      spinal cord. Treatment options are limited due to the complexity of underlying
      disease factors. Cell therapy, using human umbilical cord blood (hUCB) cells may
      be a promising new treatment for ALS, mainly by providing a protective
      microenvironment for motor neuron survival. Areas covered: Composition, in vitro
      and in vivo differentiation of hUCB cells, and the advantages of cord blood as a
      source of transplant cells are discussed. A brief history of hUCB in treatment of
      an ALS animal model and the feasibility of these cells in therapy for ALS
      patients is provided. Current ALS clinical trials are also deliberated. Expert
      opinion: Among multiple advantages, hUCB cells' production of various anti
      inflammatory/growth/trophic factors makes them an attractive cell source for ALS
      therapy. Biodistribution and optimal hUCB cell dose for transplantation have been
      determined in preclinical studies. Repeated intravenous cell doses during disease
      progression may be the best approach for cell-based ALS treatment. Accumulated
      evidence shows the efficacy of naive or genetically modified MNC hUCB cells in
      the treatment of ALS and provide a superior basis for the development of clinical
      trials in the near future.

PMID- 28443373
TI  - Association Between Women's Empowerment and Maternal and Child Nutrition in
      Kalale District of Northern Benin.
AB  - BACKGROUND: Evidence on effectiveness of women's empowerment (WE) to reduce
      undernutrition is limited in sub-Sahara Africa, and few studies incorporate
      multidimensional measures of WE. OBJECTIVE: To examine whether a WE status, in
      sum and across leadership, decision-making, mobility, economic security, male
      involvement in housework, and nonfamily group domains, is associated with women
      and their children nutritional status in Kalale district of northern Benin.
      METHODS: Data were obtained from the 2014 Solar Market Garden baseline study: 767
      paired reproductive-age women aged 15 to 49 years and children 6 to 59 months
      old. Exploratory principal component (cross-validate with confirmatory) factor
      analysis was first conducted to identify the structure of empowerment. Then,
      using a new survey-based index, regression analysis was conducted to examine
      associations between WE measures and maternal dietary diversity score (DDS) and
      body mass index (BMI), as well as their child's DDS, height-for-age z score
      (HAZ), weight-for-height z score (WHZ), and weight-for-age z score (WAZ).
      RESULTS: Positive associations were observed between women's composite
      empowerment, leadership, maternal DDS and BMI, and female child's DDS. However,
      opposite signs were found between economic security and child's DDS. Mobility was
      positively associated with female children's WHZ and male children's HAZ and WAZ,
      while decision-making was correlated with male child's WHZ and female children's
      WAZ. CONCLUSIONS: Women's empowerment can be associated with undernutrition.
      Efforts to improve nutrition may benefit from empowerment initiatives that
      promote women's self-confidence and decision-making in Benin. However, additional
      qualitative and longitudinal research may enhance understanding of WE in the
      present area.

PMID- 28443374
TI  - Is it really safe to withhold folinic acid when less than 1000 mg/m2 methotrexate
      is ingested?

PMID- 28443375
TI  - Human fatalities caused by animal attacks: A six-year autopsy study.
AB  - Deaths caused by animal attacks in urban as well as rural areas are rising. With
      dwindling forest cover and with more interaction of animals with humans in day-to
      day life, we need to understand the reasons, manner and causes of these fatal
      events. We studied 151 cases of fatal animal/human conflicts and in particular,
      the manner and mechanism of causation of injuries with respect to different types
      of animals. In this region there were more fatal snake bites followed by cattle
      attacks. Humans are at some risk while in the vicinity of animals whether in the
      wild or in human settlements. Human/animal conflicts occur due to reducing
      habitat for animals and the demands of humans. One must be aware of the potential
      dangers from animals and as a health care provider it is our duty to educate the
      public at large. They need to be cautious when around animals, seek medical care
      after an animal injury and wear protective equipment when working around or with
      animals.

PMID- 28443376
TI  - Remote Ischemic Conditioning and Renal Protection.
AB  - Over the course of the last 2 decades, the concept of remote ischemic
      conditioning (RIC) has attracted considerable research interest, because RIC, in
      most of its embodiments offers an inexpensive way of protecting tissues against
      ischemic damage inflicted by a number of medical conditions or procedures. Acute
      kidney injury (AKI) is a common side effect in the context of various medical
      procedures, and RIC has been suggested as a means of reducing its incidence.
      Outcomes regarding kidney function have been reported in numerous studies that
      evaluated the effects of RIC in a variety of settings (eg, cardiac surgery,
      interventions requiring intravenous administration of contrast media). Although
      several individual studies have implied a beneficial effect of RIC in preserving
      kidney function, 3 recently published randomized controlled trials evaluating
      more than 1000 patients each (Effect of Remote Ischemic Preconditioning in the
      Cardiac Surgery, Remote Ischaemic Preconditioning for Heart Surgery, and ERICCA)
      were negative. However, AKI or any other index of renal function was not a stand
      alone primary end point in any of these trials. On the other hand, a range of
      meta-analyses (each including thousands of participants) have reported mixed
      results, with the most recent among them showing benefit from RIC, pinpointing at
      the same time a number of shortcomings in published studies, adversely affecting
      the quality of available data. The present review provides a critical appraisal
      of the current state of this field of research. It is the opinion of the authors
      of this review that there is a clear need for a common clinical trial framework
      for ischemic conditioning studies. If the current babel of definitions,
      procedures, outcomes, and goals persists, it is most likely that soon ischemic
      conditioning will be "yesterday's news" with no definitive conclusions having
      been reached in terms of its real clinical utility.

PMID- 28443377
TI  - Association of MicroRNA-146a and MicroRNA-149 Polymorphisms With Strokes in Asian
      Populations: An Updated Meta-Analysis.
AB  - Strokes are a major cause of disability and death worldwide. An association
      between microRNA-146a (miR-146a) and miR-149 polymorphisms and strokes was
      inconclusive. This meta-analysis aimed to reevaluate the strength of the
      association by searching online databases and retrieving relevant case-control
      studies published between 2000 and 2016. Nine articles including 8 on miR-146a
      rs2910164 G/C and 3 on miR-149 rs2292832 C/T in 3372 patients with stroke and
      4394 controls were included. The miR-149 rs2292832 was significantly associated
      with the risk of a stroke under allelic (C vs T: odds ratio [OR] = 1.14; 95%
      confidence interval [CI] = 1.01-1.29; P = .03), homologous (CC vs TT: OR = 1.36;
      95% CI = 1.05-1.77; P = .02), and recessive models (CC vs CT + TT: OR = 1.34; 95%
      CI = 1.05-1.71; P = .02). No correlation was detected between miR-146a rs2910164
      and susceptibility to a stroke. In conclusion, the results suggested that miR-149
      might be a risk factor for the development of a stroke, while miR-146a might not
      be. Well-designed studies with large populations are needed to clarify the
      association between miR-146a and miR-149 polymorphisms and strokes.

PMID- 28443378
TI  - Toxicity resulting from exposure to oven cleaners as reported to the UK National
      Poisons Information Service (NPIS) from 2009 to 2015.
AB  - INTRODUCTION: Oven cleaning products contain corrosive substances, typically
      sodium or potassium hydroxide. OBJECTIVE: To determine the reported toxicity from
      exposure to oven cleaning products. METHODS: Telephone enquiries to the UK
      National Poisons Information Service regarding oven cleaning products were
      analysed retrospectively for the period January 2009 to December 2015. RESULTS:
      There were 796 enquiries relating to 780 patients. Ninety-six percent of the
      products involved in the reported exposures contained sodium hydroxide and/or
      potassium hydroxide. Ingestion alone (n = 285) or skin contact alone (n = 208)
      accounted for the majority of cases; inhalation alone (n = 101), eye contact
      alone (n = 97), and multiple routes of exposure (n = 89) accounted for the
      remainder. Ninety-five percent of patients exposed by inhalation, 94% exposed
      dermally and 85% reporting eye exposure, developed features of toxicity. Patients
      exposed by multiple routes developed symptoms in 70% of cases. Only 103 of the
      285 patients ingested oven cleaner directly, whereas 182 patients ingested food
      they considered to have been contaminated with oven cleaner. In 100 of the 103
      direct ingestions where the features and World Health Organisation/International
      Programme on Chemical Safety/European Commission/European Association of Poison
      Centres and Clinical Toxicologists Poisoning Severity Score were known, 56
      reported symptoms which were minor in 51 cases. The most common features
      following ingestion were vomiting (n = 26), abdominal pain (n = 22) or
      pharyngitis (n = 15). Skin burns (n = 91) predominantly involving the hands or
      arms, occurred in 44% of dermal exposures. Following inhalation, patients
      frequently developed respiratory features (n = 52) including coughing and chest
      pain/tightness. Eye pain (n = 43) and conjunctivitis (n = 33) commonly occurred
      following ocular exposure. CONCLUSIONS: Most (71%) patients exposed to an oven
      cleaner irrespective of the route of exposure developed features of toxicity,
      though in most cases only minor features developed; moderate or severe features
      ensued in ~4%. Those patients exposed dermally, ophthalmically or by inhalation
      developed features more frequently (>=85%) than those who ingested a product
      directly (56%).

PMID- 28443379
TI  - Informed consent for cord tissue collection in a North Eastern Italy region. A
      matter of inadequate health legislation?

PMID- 28443380
TI  - Acute hypersensitivity reaction to Crotalidae polyvalent immune Fab (CroFab) as
      initial presentation of galactose-alpha-1,3-galactose (alpha-gal) allergy.
AB  - Crotalidae polyvalent immune Fab antivenom (CroFab), commonly used for the
      treatment of clinically significant North American crotalinae envenomation, is
      generally well-tolerated. A novel form of anaphylaxis due to an IgE antibody
      response to the mammalian oligosaccharide galactose-alpha-1,3-galactose (alpha
      gal) has been established following red-meat consumption as well as IV
      administration of cetuximab, which contain the alpha-gal epitope. We present a
      case of alpha-gal allergy discovered after acute hypersensitivity reaction to
      FabAV. A 61-year-old healthy female was bitten on her left ankle by Agkistrodon
      contortrix. Given the patient's rapid progression of pain and swelling, she was
      given FabAV. During infusion of FabAV, she developed diffuse hives over her
      entire body and itching, but denied respiratory or gastrointestinal symptoms and
      her vital signs remained stable. The FabAV was immediately discontinued and she
      received intravenous diphenhydramine and famotidine with gradual resolution of
      symptoms. On further discussion, she denied a history of alpha-gal or papaya
      allergy but rarely ate red meat and endorsed sustaining frequent tick bites.
      Subsequent antibody testing was significant for an alpha-1,3-galactose IgE
      concentration of 45,000 U/L (normal <3500 U/L), confirming alpha-gal allergy. To
      our knowledge, this is the first report of FabAV hypersensitivity associated with
      an underlying alpha-gal allergy.

PMID- 28443382
TI  - Diagnostic imaging modalities and surgical anatomy of the temporomandibular joint
      in rabbits.
AB  - The temporomandibular joint (TMJ) is a condylar synovial joint that, together
      with the masticatory muscles, controls mandibular movement during mastication.
      The rabbit is often used as a model species for studying the mechanisms of TMJ
      diseases, and in regenerative research. However, there are significant
      differences between rabbit and human TMJs that should be taken into account
      before using this model for experimental research. Here, we use several
      analytical approaches (radiography, computed tomography and magnetic resonance
      imaging) to enable a detailed description and analysis of the rabbit TMJ
      morphology. Moreover, possible surgical approaches have been introduced with a
      focus on available access into the rabbit TMJ cavity, which relate our findings
      to clinical usage.

PMID- 28443381
TI  - Pharmacological management of narcolepsy with and without cataplexy.
AB  - INTRODUCTION: Narcolepsy is an orphan neurological disease and presents with
      sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with
      cataplexy is most commonly caused by an immune-mediated process including genetic
      and environmental factors, resulting in the selective loss of hypocretin
      producing neurons. Narcolepsy has a major impact on workableness and quality of
      life. Areas covered: This review provides an overview of the temporal available
      treatment options for narcolepsy (type 1 and 2) in adults, including
      authorization status by regulatory agencies. First- and second-line options are
      discussed as well as combination therapies. In addition, treatment options for
      frequent coexisting co-morbidities and different phenotypes of narcolepsy are
      presented. Finally, this review considers potential future management strategies.
      Non-pharmacological approaches are important in the management of narcolepsy but
      will not be covered in this review. Expert opinion: Concise evaluation of
      symptoms and type of narcolepsy, coexisting co-morbidities and patients' distinct
      needs is mandatory in order to identify a suitable, individual pharmacological
      treatment. First-line options include Modafinil/Armodafinil (for excessive
      daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant
      (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid
      depression). New symptomatic and causal treatment most probably will be completed
      by hypocretin-replacement and immune-modifying strategies.

PMID- 28443383
TI  - Beneficial effects of Lactobacillus casei strain Shirota on academic stress
      induced sleep disturbance in healthy adults: a double-blind, randomised, placebo
      controlled trial.
AB  - The present study examined whether Lactobacillus casei strain Shirota (LcS)
      improves sleep quality under psychological stress. A double-blind, placebo
      controlled trial was conducted in healthy 4th year medical students exposed to
      academic examination stress. The trial was repeated over two consecutive years in
      different groups of students, and the data were pooled. For 8 weeks prior to and
      3 weeks after a national standardised examination, a total of 48 and 46 subjects
      received a daily dose of 100 ml of LcS-fermented milk or non-fermented placebo
      milk, respectively. Study measures included subjective anxiety, overnight single
      channel electroencephalography (EEG) recordings, and the Oguri-Shirakawa-Azumi
      (OSA) sleep inventory scores of subjective sleep quality. Total OSA scores were
      significantly lower than baseline on the day before the exam and recovered after
      the exam, indicating a stress-induced decline in sleep quality. There was a
      significant positive effect of LcS treatment on OSA factors for sleepiness on
      rising and sleep length. Sleep latency measured by EEG lengthened as the exam
      approached in the placebo group but was significantly suppressed in the LcS
      group. The percentage of stage 3 non-REM (N3) sleep decreased in the placebo
      group as the exam approached, whereas it was maintained in the LcS group
      throughout the trial. Delta power during the first sleep cycle, measured as an
      index of sleep intensity, increased as the exam approached in the LcS group and
      was significantly higher than in the placebo group. These findings suggest that
      daily consumption of LcS may help to maintain sleep quality during a period of
      increasing stress. The observed retention of N3 sleep and increased delta power
      in the LcS group may have contributed to higher perceived sleep satisfaction.

PMID- 28443384
TI  - Biological and targeted therapies of systemic lupus erythematosus: evidence and
      the state of the art.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a multi-systemic disease
      characterized by an unpredictable disease course and periods of remission and
      flare, leading to organ damage and mortality. Novel biological agents are being
      developed (targeting the lymphocytes, accessory molecules and cytokines) that aim
      to enhance the therapeutic efficacy when combined with standard therapies. Areas
      covered: This article updates recent data on the use of biological and targeted
      therapies in SLE. Expert commentary: B cells remain the main target of
      development of novel therapeutics in SLE. Similar to the intravenous preparation,
      subcutaneous belimumab has been shown to be superior to placebo when added to the
      standard of care in SLE. However, two phase III trials of epratuzumab and
      blisibimod did not meet their primary endpoints. Recent data on the inhibition of
      type I interferons (anifrolumab) appear promising. Newer calcineurin inhibitors
      and combination strategies using conventional immunosuppressive agents are being
      tested in lupus nephritis. Finally, international groups are developing consensus
      definitions on disease remission and low disease activity state to explore the
      benefits of the treat-to-target strategy in SLE. Hopefully, the armamentarium for
      the treatment of SLE can be expanded in the near future, so that the longevity
      and quality of life of patients can be further improved.

PMID- 28443385
TI  - Pseudomonas aeruginosa prevalence, antibiotic resistance and antimicrobial use in
      Chinese burn wards from 2007 to 2014.
AB  - Objective To assess the application of antibacterial agents, alongside pathogen
      prevalence and Pseudomonas aeruginosa drug resistance, with the aim of
      understanding the impact of inappropriate antibacterial use. Methods This
      retrospective study assessed bacteria from wounds, catheters, blood, faeces,
      urine and sputum of hospitalized patients in burn wards between 2007 and 2014.
      The intensity of use of antibacterial agents and resistance of P. aeruginosa to
      common anti-Gram-negative antibiotics were measured. Results Annual detection
      rates of Staphylococcus aureus were significantly decreased, whereas annual
      detection rates of P. aeruginosa and Klebsiella pneumoniae were significantly
      increased. Multidrug-resistant strains of P. aeruginosa were increased. The
      intensity of use of some anti-Gramnegative antibiotics positively correlated with
      resistance rates of P. aeruginosa to similar antimicrobials. Conclusion In burn
      wards, more attention should be paid to P. aeruginosa and K. pneumoniae. The use
      of ciprofloxacin, ceftazidime and cefoperazone/sulbactam should be limited to
      counter the related increase in resistance levels.

PMID- 28443386
TI  - Association of renal function and symptoms with mortality in star fruit (Averrhoa
      carambola) intoxication.
AB  - BACKGROUND: Star fruit (SF) is a commonly available fruit produced and eaten in
      tropical and subtropical countries. Since 1993, various reports have described
      neurotoxicity after eating SF, but this clinical condition remains unfamiliar. We
      aimed to describe this clinical entity, the role of renal dysfunction in this
      disorder, treatment strategies, and prognosis of patients with SF intoxication.
      METHODS: We conducted a search of PubMed and Google Scholar databases from 1993
      to 2016. We included reports describing patients with a clear history of SF
      ingestion with acute symptoms. We described the demographic characteristics,
      reported SF intake, treatments used, and outcomes. RESULTS: We reviewed totally
      126 patients (male:female = 1.5:1) from 33 articles with mean age 54.4 +/- 11
      (range: 30-84). The most common symptom was hiccups (65%), whereas confusion and
      seizure were the most common symptoms associated with mortality (42% and 61%,
      respectively). Pre-intoxication renal function also affected mortality. While
      there was no mortality in patients with normal renal function (NRF), the
      mortality of patients among reported cases with chronic renal insufficiency and
      end-stage renal disease undergoing dialysis were 36% and 27%, respectively. With
      the inclusion of patients reported to have NRF, the overall mortality was 24%.
      Consistently, the number of SF consumed was substantially higher in the patients
      with NRF than those with renal functional impairment. The most common treatment
      strategy was hemodialysis (59%). CONCLUSIONS: Patients with impaired renal
      function were at higher risks of SF intoxication. Severe neurologic symptoms
      mandate immediate medical intervention because of the association between their
      occurrence and high mortalities. Toxin removal through dialysis, rather than
      symptomatic relief, seems to be beneficial to patient survival. Early and
      continuous dialysis appears to alleviate severe symptoms and prevent symptom
      rebounds.

PMID- 28443387
TI  - Microwave-activated carbons from tucuma (Astrocaryum aculeatum) seed for
      efficient removal of 2-nitrophenol from aqueous solutions.
AB  - Activated carbons (ACs) prepared from tucuma seed (Astrocaryum aculeatum) were
      used for 2-nitrophenol removal from aqueous solutions. The ACs were characterized
      by elemental analysis, FTIR, N2 adsorption/desorption isotherms, TGA,
      hydrophobicity/hydrophilicity balance, and total of acidic and basic groups. The
      ACs showed to have hydrophilic surfaces and they presented high specific surface
      areas (up to 1318 m2 g-1). In batch optimization studies, maximum removal was
      obtained at pH 7, contact time of 30 min, adsorbent dosage 1.5 gL-1 and
      temperature of 50 degrees C. The general-order kinetic model and Liu isotherm
      model best fit the kinetic and equilibrium adsorption data with a maximum
      adsorption capacity of 1382 mg g-1 at 50 degrees C. Effect of temperature and
      thermodynamic studies revealed that the adsorption processes of 2-nitrophenol
      onto ACs are dependent on temperature and are exothermic and spontaneous,
      respectively. About the applicability of the ACs for treating simulated
      effluents, the tucuma seed-activated carbon showed an excellent outcome in the
      treatment of simulated effluents, evidencing its high efficiency for phenolic
      compound adsorption. Tucuma seed-ACs showed to be cost effective and highly
      efficient adsorbents for efficient removal of 2-nitrophenol from aqueous
      solutions.

PMID- 28443388
TI  - Utilization of Thoracic Ultrasound for Confirmation of Central Venous Catheter
      Placement and Exclusion of Pneumothorax: A Novel Technique in Real-Time
      Application.
AB  - AIM: To evaluate the safety and utility of ultrasonography as a tool to confirm
      central venous catheter (CVC) position and to exclude insertion-related
      pneumothorax in place of chest radiography (CXR) in a tertiary medical intensive
      care unit (ICU). METHODS: We randomized 60 consecutive medical ICU patients to
      conventional or ultrasound groups for CVC placement. Both groups had CVCs
      inserted under ultrasound guidance. The intervention group underwent real-time
      transthoracic echocardiography to assist in catheter positioning and chest
      ultrasonography for exclusion of pneumothorax. Our primary end point was
      reduction in CXR use. The secondary end point was time elapsed from the end of
      procedure to the availability of CVC for use. chi2 test was used to compare the 2
      groups for the primary end point. T test was used to compare the 2 groups for the
      secondary end point. RESULTS: Thirty patients were randomized to the conventional
      group and 30 were randomized to the ultrasound group. One patient was excluded in
      the control group since the procedure needed to be aborted. Patient
      characteristics were well matched for age, body mass index, and acute physiologic
      assessment and chronic health evaluation (APACHE III) scores. There was a 56.7% (
      P < .0001) reduction in CXR use in the ultrasound arm. Mean time to use was 53.6
      minutes in the control group and 25 minutes in the ultrasound arm ( P = .0015).
      Mean time required to complete the procedure was 27.7 minutes in the control
      group and 24.1 minutes in the ultrasound group ( P = .2053). No pneumothorax was
      detected in either arm. CONCLUSION: Ultrasound-guided CVC placement and
      positioning with a minor modification in technique reduced the use of bedside CXR
      and reduced the time to use of the CVC.

PMID- 28443389
TI  - Neuroscience Intermediate-Level Care Units Staffed by Intensivists: Clinical
      Outcomes and Cost Analysis.
AB  - INTRODUCTION: With an aging population and increasing numbers of intensive care
      unit admissions, novel ways of providing quality care at reduced cost are
      required. Closed neurointensive care units improve outcomes for patients with
      critical neurological conditions, including decreased mortality and length of
      stay (LOS). Small studies have demonstrated the safety of intermediate-level
      units for selected patient populations. However, few studies analyze both cost
      and safety outcomes of these units. This retrospective study assessed clinical
      and cost-related outcomes in an intermediate-level neurosciences acute care unit
      (NACU) before and after the addition of an intensivist to the unit's care team.
      METHODS: Starting in October 2011, an intensivist-led model was adopted in a 16
      bed NACU unit, including daytime coverage by a dedicated intensivist. Data were
      obtained from all patients admitted 1 year prior to and 2 years after this
      intervention. Primary outcomes were LOS and hospital costs. Safety outcomes
      included mortality and readmissions. Descriptive and analytic statistics were
      calculated. Individual and total patient costs were calculated based on per-day
      NACU and ward cost estimates and significance measured using bootstrapping.
      RESULTS: A total of 2931 patients were included over the study period. Patients
      were on average 59.5 years and 53% male. The most common reasons for admission
      were central nervous system (CNS) tumor (27.6%), ischemic stroke (27%), and
      subarachnoid hemorrhage (11%). Following the introduction of an intensivist,
      there was a significant reduction in NACU and hospital LOS, by 1 day and 3 days,
      respectively. There were no differences in readmissions or mortality. Adding an
      intensivist produced an individual cost savings of US$963 in NACU and US$2687 per
      patient total hospital stay. CONCLUSION: An intensivist-led model of intermediate
      level neurointensive care staffed by intensivists is safe, decreases LOS, and
      produces cost savings in a system increasingly strained to provide quality
      neurocritical care.

PMID- 28443390
TI  - An Integrative Index for Predicting Extubation Outcomes After Successful
      Completion of a Spontaneous Breathing Trial in an Adult Medical Intensive Care
      Unit.
AB  - BACKGROUND: Among respiratory predictors, rapid shallow breathing index (RSBI)
      has been a commonly used respiratory parameter to predict extubation outcomes.
      However, the outcome of prediction remains inconsistent. Regarding nonrespiratory
      predictors, serum albumin, hemoglobin, bicarbonate, and patients' alertness have
      been reported to be associated with successful weaning or extubation. We aimed to
      develop an integrative index combining commonly used predictors in the adult
      medical intensive care units (MICUs) and to compare the predictability of the
      index with RSBI. METHODS: This prospective observational study with retrospective
      data collection of planned extubations was conducted in a 14-bed adult MICU. We
      enrolled patients who received mechanical ventilation via an endotracheal tube in
      the adult MICU for >24 hours and passed a 2-hour spontaneous breathing trial and
      underwent extubation. Extubation failure was defined as reinstitution of invasive
      mechanical ventilation within 48 hours of extubation. Respiratory parameters and
      Glasgow Coma Scale (GCS) scores of patients were recorded prospectively.
      Nonrespiratory parameters were recorded retrospectively. Logistic regression was
      used to determine significant predictors of extubation outcomes. RESULTS: Fifty
      nine patients comprising 70 extubations were enrolled. Extubation failure was
      significantly and positively associated with lower serum albumin (albumin < 2.6
      g/dL, odds ratio [OR] = 5.1; 95% confidence interval [CI], 1.04-24.66), lower
      hemoglobin (hemoglobin < 10.0 g/dL, OR = 10.8; 95% CI, 2.00-58.04), and lower GCS
      scores (GCS score <= 8, OR = 6.1; 95% CI = 1.15-32.34). By using an integrative
      index combining the 3 parameters together, the sensitivity and specificity to
      predict extubation outcomes were 78.6% and 75.9%, respectively. The area under
      the receiver operating characteristic curve of the index was significantly higher
      than RSBI (0.84 vs 0.61, P = .026). CONCLUSION: The integrative index combining
      serum albumin, hemoglobin, and GCS scores could predict extubation outcomes
      better than RSBI in an adult MICU.

PMID- 28443391
TI  - Atazanavir sulfate + cobicistat for the treatment of HIV infection.
AB  - INTRODUCTION: During last two decades several drugs were developed to offer long
      term benefits in terms of virologic efficacy, favourable tolerability and
      toxicity profiles in treatment of HIV infection. Pharmacokinetics boosting of
      protease inhibitor allows a higher genetic barrier, as few or no drug-resistant
      mutations are detected in patients with virologic failure. Areas covered:
      Atazanavir sulfate + cobicistat (ATV/c) was recently approved for the treatment
      of HIV-1 infection. Bioequivalence between cobicistat (COBI) and ritonavir (RTV)
      as a pharmacoenhancer of ATV was established. Additionally, randomized clinical
      trials demonstrated that ATV/c and ATV/ritonavir had comparable efficacy and
      safety profiles. Low rates of virologic failure and no ATV resistance mutations
      were observed in these clinical trials. Therefore, COBI shows increased
      advantages over RTV, such as no activity against HIV, fewer drug-drug
      interactions and better solubility, which promotes coformulation strategies with
      less pill burden, better tolerability, and, potentially, higher life-long
      treatment adherence. Expert commentary: ATV/c regimen supports its useas an
      effective treatment option for HIV-1 infected patients with increased
      cardiovascular disease and chronic kidney disease risk associated with aging. In
      addition, ATV/c is a new opportunity to expand the strategy of switch to a dual
      therapy to lower the risk of long-term toxicities as well as the advantage of its
      cost-benefit.

PMID- 28443392
TI  - Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in
      vivo but not ex vivo in healthy humans.
AB  - Clinical data indicate that inflammatory responses differ across sexes, but the
      mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine
      responses to bacterial endotoxin in healthy men and women to elucidate the role
      of systemic and cellular factors underlying sex differences in inflammatory
      responses. Participants received an i.v. injection of low-dose endotoxin (0.4
      ng/kg body mass), and plasma TNF-alpha and IL-6 responses were analyzed over a
      period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin
      stimulated blood samples obtained immediately before in vivo endotoxin
      administration. As glucocorticoids (GCs) play an important role in the negative
      feedback regulation of the inflammatory response, we additionally analyzed plasma
      cortisol concentrations and ex vivo GC sensitivity of cytokine production.
      Results revealed greater in vivo pro-inflammatory responses in women compared
      with men, with significantly higher increases in plasma TNF-alpha and IL-6
      concentrations. In addition, the endotoxin-induced rise in plasma cortisol was
      more pronounced in women. In contrast, no sex differences in ex vivo cytokine
      production and GC sensitivity were observed. Together, these findings demonstrate
      major differences in in vivo and ex vivo responses to endotoxin and underscore
      the importance of systemic factors underlying sex differences in the inflammatory
      response.

PMID- 28443394
TI  - Spotting the odd one out.
AB  - Andrew Haydon's article 'Where are all the male nursing students?' was good, but
      it will be to no avail (students, 12 April).

PMID- 28443395
TI  - Living colour.
AB  - A nurse has used the everyday tools of her trade to create a colourful artwork.

PMID- 28443396
TI  - Unfair decision.
AB  - The recent cautioning of nurse Jane Kendall by the NMC for not beginning
      cardiopulmonary resuscitation (CPR) on a deceased patient left me feeling like
      the world had gone topsy-turvy (features, 12 April).

PMID- 28443393
TI  - CD14 gene silencing alters the microRNA expression profile of RAW264.7 cells
      stimulated by Brucella melitensis infection.
AB  - Innate recognition of Brucella spp. is a key step in the activation of
      inflammation. CD14 binds PAMPs and is involved in LPS-induced pro-inflammatory
      cytokine release. Previously we showed that knock down of CD14 in RAW264.7
      macrophages disrupted Brucella-host interactions. However, its effect on the
      macrophage microRNA (miRNA) expression profile, especially after stimulation by
      Brucella infection, is still unclear. To identify miRNAs involved in the
      macrophage response to Brucella infection, we performed miRNA expression
      profiling of CD14 knock-down RAW264.7 (224.3) macrophages infected with Brucella
      melitensis, and demonstrated, for the first time, that CD14 knock down
      significantly up-regulated the expression of mmu-miR-199a-3p and mmu-miR-183-5p
      in these conditions. These miRNAs have a well-characterized association with the
      target genes involved in immune response, inflammatory response, innate immune
      response, apoptosis processes, anti-apoptosis, cytokine production and cytokine
      mediated signaling pathways. Among the 104 inflammation-related candidate target
      genes of mmu-miR-199a-3p and mmu-miR-183-5p in the 224.3+ B. melitensis group
      cells, the expression of the Cbl-b, a potential target of mmu-miR-199a-3p, was
      confirmed to be down-regulated using qRT-PCR and Western blot analysis. Our
      findings suggest that CD14 functions in the Brucella-host interaction may be
      through altered miRNA expression, and regulation of Cbl-b proteins.

PMID- 28443398
TI  - Andrew Parker Student Nurse Award in association with RCN Fellows.

PMID- 28443397
TI  - See the person behind the patient.
AB  - During my first clinical placement on a surgical ward, I helped care for a female
      patient with peritoneal cancer. The patient, who I will call Jane, was about 60
      years old and was receiving palliative care.

PMID- 28443399
TI  - Mental Health Practice Award.

PMID- 28443400
TI  - 'In my experience...'.
AB  - Nurses are a wise group, but we aren't always smart enough to look after
      ourselves properly. Yes, we have the knowledge and we know that if we practised
      what we preached we could be healthier, but sometimes life just isn't that
      simple.

PMID- 28443401
TI  - 'District nurses' hands are tied by poor procurement decisions'.
AB  - In March last year my husband Steve woke up in agony, with pain in his right foot
      and leg. His toes had turned blue, and after a dash to the local emergency
      department, we were quickly referred to the vascular team at a leading London
      hospital.

PMID- 28443403
TI  - Advice for health visitors on identifying domestic slaves.
AB  - Health visitors are in a good position to spot the signs that someone is living
      as a domestic slave, according to the Institute of Health Visiting (IHV).

PMID- 28443406
TI  - eRedbook.
AB  - The NHS recently launched a digital version of the personal child health record,
      'the red book'. It aims to replace the physical book given to new parents to
      manage their child's health between 0-5 years.

PMID- 28443404
TI  - Prince's revelations about his own mental health 'a true turning point'.
AB  - Prince Harry has been praised after revealing he sought counselling to come to
      terms with the death of his mother.

PMID- 28443407
TI  - Community Nursing Award.

PMID- 28443408
TI  - Doing a Literature Review in Nursing, Health and Social Care (Second edition)
      Coughlan Michael Cronin Patricia Doing a Literature Review in Nursing, Health and
      Social Care (Second edition) 184pp L19.99 Sage Publishing 9781412962049
      1412962048 [Formula: see text].
AB  - This book provides a concise and informative guide to the process of literature
      reviewing in nursing, health and social care, and is applicable to students and
      professionals.

PMID- 28443409
TI  - Nurses and unions say 'fight for our NHS' as prime minister announces election
      date.
AB  - Nurses and health unions have urged politicians to focus on the NHS after prime
      minister Theresa May called a general election for 8 June.

PMID- 28443410
TI  - Vital signs.
AB  - A snapshot of the state of UK health and social care.

PMID- 28443411
TI  - RCNi Nurse Awards 2017.
AB  - Now in their 30th year, the RCNi Nurse Awards exist to showcase the work of
      innovative and inspirational nurses from all over the UK. The quality of entries
      in 2017 was as high as ever, bringing to light the outstanding contribution made
      by nursing staff to enhancing patient safety, outcomes and experience.

PMID- 28443412
TI  - Police assigned to protect staff at four NHS hospitals.
AB  - A police team has been assigned to protect emergency departments at four major
      hospitals in London.

PMID- 28443414
TI  - Patient's Choice Award.

PMID- 28443413
TI  - Bank Nurse Award.

PMID- 28443415
TI  - Enhancing diabetes education and self-management in South Asian populations in
      the UK.
AB  - The South Asian population in the UK is at increased risk of developing type 2
      diabetes mellitus. This article considers the cultural beliefs that South Asian
      patients with diabetes may have about their condition, and discusses the
      challenges that healthcare practitioners may encounter when providing care for
      this patient group. It offers practical advice on how to enhance the care and
      treatment of these patients, including the importance of providing culturally
      sensitive guidance. There may be particular risks and health effects for Muslim
      patients with diabetes who choose to fast during Ramadan. The principal author
      introduced a 'pre-Ramadan assessment' initiative in their GP surgery in Tower
      Hamlets, London, which aimed to provide education on the risks associated with
      fasting and to improve patients' self-management of their condition, thus
      reducing potential health complications.

PMID- 28443416
TI  - Cancer Nursing Practice Award.

PMID- 28443417
TI  - Ready to strike?
AB  - Nurses are being asked by the RCN if they want to consider industrial action -
      including going on strike - in response to low NHS pay.

PMID- 28443418
TI  - Student life - Giving evidence at an inquest.
AB  - In my first year as a mental health nursing student, I was involved in an
      incident that resulted in the death of a service user.

PMID- 28443421
TI  - Leadership Award.

PMID- 28443419
TI  - Despite gains, BME staff still face discrimination.
AB  - Black and minority ethnic (BME) staff are continuing to face discrimination in
      the NHS in England, but there are signs of improvement in a new report.

PMID- 28443422
TI  - New chiefs will aid transformation.
AB  - NHS England has announced two new directors of nursing to help tackle challenges
      facing the profession.

PMID- 28443423
TI  - RCN Healthcare Assistant Award.

PMID- 28443424
TI  - Diabetes nurse helped my daughter overcome her fear of needles.
AB  - My daughter Ashleigh was diagnosed with type 1 diabetes in 2015, aged 23. She has
      a fear of needles and has vasovagal episodes where she has a sharp dip in blood
      pressure and collapses.

PMID- 28443425
TI  - Hearing mother's voice increases stability in premature babies.
AB  - Hearing their mother's voice appears to benefit the health of premature babies, a
      study has suggested.

PMID- 28443426
TI  - Smoking remains a major cause of disability and early death.
AB  - More than one in ten deaths worldwide, about 6.4 million, are caused by smoking,
      a major study has found.

PMID- 28443427
TI  - The battle for fair pay can still be won.
AB  - This year's report from the NHS Pay Review Body (RB) contains strong words and
      stark messages listing 'public-sector pay policy under stress, significant supply
      shortages in a number of staff groups and geographical areas, widespread concerns
      about recruitment, retention and motivation, inflation set to rise and further
      real-terms pay cuts on the horizon'. In short, according to the RB, the NHS is
      reaching a tipping point.

PMID- 28443428
TI  - The MS Nurse: 25 Years on.
AB  - Emma Matthews became a multiple sclerosis (MS) specialist nurse after looking for
      a job that would let her build close relationships with patients and their
      families. Ms Matthews, who works at Northampton General Hospital four days a
      week, says working with patients to manage the progressive neurological condition
      has been incredibly satisfying.

PMID- 28443432
TI  - Marmite may help regulate healthy brain function.
AB  - Eating foods rich in B vitamins - such as the yeast extract Marmite - can boost
      chemicals associated with healthy brain function, according to researchers.

PMID- 28443431
TI  - Child Health Award.

PMID- 28443433
TI  - Overactive bladder.
AB  - What was the nature of the CPD activity, practice-related feedback and/or event
      and/or experience in your practice? The article described the symptoms and
      management of overactive bladder, as well as the potential effects on the lives
      of women with the condition.

PMID- 28443434
TI  - Pollution associated with higher rates of breast cancer risk factor.
AB  - Living in an area of high pollution may increase a woman's chance of having high
      breast density, which is a risk factor for breast cancer, a large study suggests.

PMID- 28443436
TI  - Innovations in your Specialty Award.

PMID- 28443435
TI  - ReSPECT - the emergency care planning tool.
AB  - Essential facts A new tool has been developed to help nurses discuss with a
      patient the care they wish to receive in an emergency, including cardiopulmonary
      resuscitation (CPR).

PMID- 28443437
TI  - How nurses can improve quality while controlling costs.
AB  - Health care is expensive, and nurses, like everyone else, must use resources
      responsibly. At the start of a new financial year there is usually a focus on
      budgets: how much was spent last year, what is available for next year and how
      savings will be made.

PMID- 28443438
TI  - Learning Disability Practice Award.

PMID- 28443439
TI  - 'I can't think of a better career'.
AB  - After qualifying in the 1980s, Sheila McQueen held a variety of roles in
      paediatric critical care, including advanced practitioner. She moved to academia
      in 2002 working as a senior lecturer, and became head of department for public
      health and wellbeing at Northumbria University in 2013. She has been in her
      current role as professor of nursing and continuing professional education at the
      University of Sunderland since July 2016.

PMID- 28443440
TI  - Nursing Older People Award.

PMID- 28443441
TI  - Well-being is every nurse's top priority - unless it's our own.
AB  - The recent survey by Nursing Standard and the Sunday Mirror painted a depressing
      picture of working in today's NHS.

PMID- 28443442
TI  - Readers' panel - Should a year's preceptorship be mandatory on qualifying?
AB  - Our experts consider a hot topic of the day.

PMID- 28443443
TI  - Practical aspects of performing Glasgow Coma Scale observations.
AB  - The Glasgow Coma Scale (GCS) is a tool that was developed to identify and chart
      possible changes or deterioration in a patient's level of consciousness and their
      neurological status. In 2014, the GCS marked its 40th anniversary, and further
      guidance was provided to assist healthcare practitioners with performing this
      assessment. This article discusses essential aspects of this guidance to enable
      healthcare practitioners to optimise GCS observations and their interpretation.

PMID- 28443444
TI  - Evaluation and its importance for nursing practice.
AB  - Evaluation of service delivery is an important aspect of nursing practice.
      Service evaluation is being increasingly used and led by nurses, who are well
      placed to evaluate service and practice delivery. This article defines evaluation
      of services and wider care delivery and its relevance in NHS practice and policy.
      It aims to encourage nurses to think about how evaluation of services or practice
      differs from research and audit activity and to consider why and how they should
      use evaluation in their practice. A process for planning and conducting an
      evaluation and disseminating findings is presented. Evaluation in the healthcare
      context can be a complicated activity and some of the potential challenges of
      evaluation are described, alongside possible solutions. Further resources and
      guidance on evaluation activity to support nurses' ongoing development are
      identified.

PMID- 28443445
TI  - Costs of prevention are dwarfed by the costs of failure.
AB  - The stand-out message from this year's Global Patient Safety Summit, held in
      Germany last month, is that there is big money in prevention.

PMID- 28443446
TI  - Yoga may benefit people with inflammatory bowel disease.
AB  - Yoga could help improve quality of life for people with chronic inflammatory
      bowel disease, a study has found.

PMID- 28443447
TI  - Scholarship offers chance to learn and get ahead.
AB  - Have you ever considered studying nursing practice overseas, undertaking a
      bespoke leadership programme or engaging in a clinical research project? If so, a
      Florence Nightingale Foundation scholarship could be for you.

PMID- 28443448
TI  - Letter.
AB  - Your story linking 12-hour shifts with sickness absence is an insulting view of
      the situation.

PMID- 28443449
TI  - A question of time.
AB  - Regarding your story 'Research reveals link between 12-hour shifts and sickness
      absence' (news, 12 April), I think you're more likely to be sick working ten
      short shifts in a row.

PMID- 28443451
TI  - Perils of gifts and loans.
AB  - Let's assume that this is not a reference to copyright infringement issues and
      that you are not going to let your patient keep the DVDs but are just loaning
      them for a specified period. Your manager is likely referring to an inverse gift
      giving scenario - instead of you receiving a gift from your patient, it is you
      who is giving the gift, even though it is just a loan and not a permanent gift.

PMID- 28443450
TI  - Letter.
AB  - I feel conflicted about striking over pay. I don't want patients to suffer but
      feel that this government and previous ones have abused the goodwill of health
      service workers.

PMID- 28443452
TI  - Commitment to Carers Award.

PMID- 28443453
TI  - Enough is enough.
AB  - I have worked in nursing for 36 years and never thought I'd hear myself say we
      need to strike. However, the government continually views nursing as a vocation
      that we do for the love of it, which of course we do, but it is also a highly
      qualified professional job with high levels of stress and responsibility.

PMID- 28443454
TI  - Excellence in Cancer Research Award.

PMID- 28443456
TI  - Calls for improvement in quality of hospital food.
AB  - A slug in a sandwich, a stone in a cottage pie and a Muslim patient being offered
      pork were among the hundreds of complaints made about NHS hospital food last
      year, Nursing Standard can reveal.

PMID- 28443457
TI  - More palatable approach to hospital food is welcome news.
AB  - Hospital food has such a poor reputation that it has long been the butt of jokes,
      but there are signs that some of the jibes are no longer appropriate. A Nursing
      Standard investigation suggests that there has been a small but welcome
      improvement in the standard of food being served to patients.

PMID- 28443458
TI  - Magnetic Resonance Imaging as a Noninvasive Method for Longitudinal Monitoring of
      Infusion Site Reactions Following Administration of a Novel Apomorphine
      Formulation.
AB  - Infusion site reactions are common following subcutaneous infusion of drugs. Such
      reactions can lead to discontinuation of the treatment. Therefore, assessment of
      such reactions is essential during preclinical safety studies, and magnetic
      resonance imaging (MRI) can assist in evaluation. Here, in vivo and ex vivo MRI
      evaluations were used in addition to classical histopathology to assess the
      infusion site reaction to ND0701, a novel formulation of apomorphine base
      developed for the treatment of Parkinson's disease, in comparison to the
      commercial apomorphine hydrochloride (HCl) formulation. Both formulations, each
      at two concentrations, were continuously administered subcutaneously for 20 hr to
      each of 3 male and 3 female domestic pigs. Based on MRI evaluations, there was a
      gradual decrease in the volume of the subcutaneous lesions over 4 weeks, with
      smaller lesions and quicker resolution with ND0701 at concentrations 2.5- to 5
      fold higher when compared to the commercial apomorphine HCl formulation.
      Histopathological evaluation of ND0701 revealed only minimal inflammation at the
      sites of infusion, whereas the commercial apomorphine HCl caused persistent
      inflammatory reactions and necrosis. This study provides support to the use of
      MRI in preclinical testing of subcutaneous drugs when evaluating local site
      reactions.

PMID- 28443459
TI  - Astragaloside IV sensitizes non-small cell lung cancer cells to gefitinib
      potentially via regulation of SIRT6.
AB  - Astragaloside IV, the active component of Astragalus membranaceus, exhibits
      diverse biological roles including the anti-tumor activity. In this study, we
      evaluated the chemosensitive role of astragaloside IV in non-small cell lung
      cancer cells. Cell Counting Kit-8 analysis was performed to determine cell
      viability. Real-time polymerase chain reaction and western blot were used to
      measure the messenger RNA and protein expression. Results showed that
      astragaloside IV treatment could suppress the proliferation of non-small cell
      lung cancer cells. In addition, combined treatment with astragaloside IV
      remarkably enhanced the chemosensitivity to gefitinib in three non-small cell
      lung cancer cell lines including NCI-H1299, HCC827, and A549. Furthermore,
      compared with gefitinib-treated cells, the messenger RNA expression of SIRT6 was
      obviously increased in non-small cell lung cancer cells treated with gefitinib
      combined with astragaloside IV. In addition, downregulation of SIRT6 was
      accomplished using small interference RNA technology. As a result, SIRT6
      inhibition abolished the sensitization role of astragaloside IV in non-small cell
      lung cancer cells. Taken together, these data demonstrated that astragaloside IV
      sensitized tumor cells to gefitinib via regulation of SIRT6, suggesting that
      astragaloside IV may serve as potential therapeutic approach for lung cancer.

PMID- 28443460
TI  - Augmented expression of RUNX1 deregulates the global gene expression of U87
      glioblastoma multiforme cells and inhibits tumor growth in mice.
AB  - Glioblastoma multiforme is the most common and aggressive primary brain tumor in
      adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor
      prognosis in glioblastoma multiforme patients. Recently, the transcription factor
      RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene
      expression signature; however, its independent role in this process is yet to be
      described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme
      cells in correspondence to its mediated transcriptome and genome-wide occupancy
      pattern. Overexpression of RUNX1 led to diminished tumor growth in nude and
      severe combined immunodeficiency mouse xenograft tumor model. At the molecular
      level, RUNX1 occupied thousands of genomic regions and regulated the expression
      of hundreds of target genes, both directly and indirectly. RUNX1 occupied genomic
      regions that corresponded to genes that were shown to play a role in brain tumor
      progression and angiogenesis and upon overexpression led to a substantial down
      regulation of their expression level. When overexpressed in U87 glioblastoma
      multiforme cells, RUNX1 down-regulated key pathways in glioblastoma multiforme
      progression including epithelial to mesenchymal transition, MTORC1 signaling,
      hypoxia-induced signaling, and TNFa signaling via NFkB. Moreover, master
      regulators of the glioblastoma multiforme mesenchymal phenotype including CEBPb,
      ZNF238, and FOSL2 were directly regulated by RUNX1. The data suggest a central
      role for RUNX1 as master regulator of gene expression in the U87 glioblastoma
      multiforme cell line and mark RUNX1 as a potential target for novel future
      therapies for glioblastoma multiforme.

PMID- 28443461
TI  - MiR-1202 functions as a tumor suppressor in glioma cells by targeting Rab1A.
AB  - Aberrant expression of microRNAs correlates with the development and progression
      of human cancers by targeting downstream proteins. MiR-1202 is downregulated in
      ovarian cancer and clear cell papillary renal cell carcinoma; however, its role
      in glioma remains unknown. The purpose of this study was to determine the
      expression and the role of miR-1202 and to elucidate its regulatory mechanism in
      glioma. We used quantitative real-time polymerase chain reaction to measure miR
      1202 expression in both glioma tissues and cell lines. The findings showed that
      the miR-1202 expression decreased dramatically in clinical glioma tissues and
      cell lines, and miR-1202 expression was inversely correlated with the expression
      of Rab1A. Using bioinformatics and luciferase reporter assays, we identified
      Rab1A as a novel and direct target of miR-1202. In vitro, overexpression of miR
      1202 inhibited glioma cell proliferation and induced endoplasmic reticulum stress
      and apoptosis through targeting Rab1A, whereas suppression of miR-1202 promoted
      cell proliferation and inhibited endoplasmic reticulum stress and apoptosis.
      Similarly, silencing Rab1A with small interfering RNA also suppressed glioma cell
      growth and induced endoplasmic reticulum stress and apoptosis. Taken together,
      our data indicate that miR-1202 suppresses proliferation and induces endoplasmic
      reticulum stress and apoptosis through targeting and inhibiting Rab1A in glioma
      cells. These results suggest miR-1202 as a potential therapeutic target for the
      treatment of glioma patients.

PMID- 28443462
TI  - BIIB021: A novel inhibitor to heat shock protein 90-addicted oncology.
AB  - Heat shock protein 90 is induced in response to the cell stress. Its
      overexpression has been reported in many cancers with poor prognosis. It acts as
      a chaperone to the client proteins, especially the activated oncoproteins in
      malignancies to protect them from degradation. Heat shock protein 90 inhibition
      represented anti-cancer effects in many studies. Previous natural product-based
      compounds are limited by their association with target toxicities. BIIB021 is an
      orally available, fully synthetic novel small-molecule heat shock protein 90
      inhibitor that has shown strong antitumor activities in a large number of
      preclinical models and is now under clinical investigation. This review will
      summarize its therapeutic effects and highlight the prospect of targeting heat
      shock protein 90 in the cancer therapy.

PMID- 28443463
TI  - Decreased expression of hsa_circ_0001895 in human gastric cancer and its clinical
      significances.
AB  - Circular RNAs are a special class of endogenous RNAs characterized by jointing 3'
      and 5' ends together via exon or intron circularization. Recent studies found
      that circular RNAs are involved in the development of some human diseases.
      However, little is known about their roles in human gastric cancer. In this
      study, we chose hsa_circ_0001895 as a targeted circRNA to investigate its
      clinical significances in gastric cancer patients. Hsa_circ_0001895 expression
      levels in five gastric cancer cell lines and 257 specimens of tissues were
      measured by real-time quantitative reverse transcription polymerase chain
      reaction. Then, the potential relationship between hsa_circ_0001895 expression
      levels and patients' clinicopathological factors was investigated. A receiver
      operating characteristic curve was constructed for evaluating the diagnostic
      value of hsa_circ_0001895. Hsa_circ_0001895 expression levels in five detected
      gastric cancer cell lines (AGS, BGC-823, HGC-27, MGC-803, and SGC-7901) were all
      significantly downregulated than those in normal gastric epithelial GES-1 cells.
      Besides, compared with healthy control tissues, it was downregulated not only in
      69.8% (67/96) gastric cancer tissues but also in gastric precancerous lesions.
      Moreover, hsa_circ_0001895 expression levels were significantly correlated with
      cell differentiation, Borrmann type, and tissue carcino-embryonic antigen
      expression. Our results suggested that hsa_circ_0001895 may play crucial roles
      during gastric cancerogenesis and is a potential biomarker for clinical prognosis
      prediction.

PMID- 28443464
TI  - Increased HAGLR expression promotes non-small cell lung cancer proliferation and
      invasion via enhanced de novo lipogenesis.
AB  - Lung cancers are broadly classified into small cell lung cancer and non-small
      cell lung cancer, with non-small cell lung cancer one of the leading causes of
      cancer-associated deaths worldwide. Presently, the mechanisms underlying lung
      tumorigenesis remain incompletely understood. Accumulating evidence indicates
      that abnormal expression of long non-coding RNAs is associated with tumorigenesis
      in multiple cancers, including lung cancer. HAGLR messenger RNA of non-small cell
      lung cancer tissues was significantly higher. Moreover, high levels of HAGLR
      expression were associated with non-small cell lung cancer tumor lymph node
      metastasis status, stage, and poor overall survival. Inhibition of HAGLR in non
      small cell lung cancer cells suppressed cell proliferation and invasion. RNA
      interference-mediated downregulation of HAGLR also decreased levels of fatty acid
      synthase, with fatty acid synthase levels positively correlated with HAGLR
      expression in non-small cell lung cancer specimens. In addition, the cellular
      free fatty acid content of cancer cells was decreased following HAGLR knockdown.
      HAGLR depletion significantly inhibited the growth of non-small cell lung cancer
      cells in vivo. Furthermore, the expression levels of p21 and matrix
      metallopeptidase-9 (MMP-9) were dysregulated when HAGLR expression was
      suppressed. Our results suggest that HAGLR is an important regulator of non-small
      cell lung cancer cell proliferation and invasion, perhaps by regulating fatty
      acid synthase. Therefore, targeting HAGLR may be a possible therapeutic strategy
      for non-small cell lung cancer.

PMID- 28443465
TI  - Bauerenol, a triterpenoid from Indian Suregada angustifolia: Induces reactive
      oxygen species-mediated P38MAPK activation and apoptosis in human hepatocellular
      carcinoma (HepG2) cells.
AB  - The triterpenoid, bauerenol, from Suregada angustifolia (Baill. ex Muell.-Arg.)
      Airy Shaw (Euphorbiaceae) was screened for anti-cancer property using
      hepatocellular carcinoma cell line, HepG2. Bauerenol exhibited growth inhibitory
      and apoptosis inducing potential against HepG2 cancer cells. 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxic assay revealed
      that bauerenol treatment significantly reduced the growth of HepG2 cells in a
      time- and dose-dependent manner with 50% growth inhibitory concentration doses of
      45 and 25 ug/mL at 24 and 48 h treatments, respectively. Bauerenol-induced cell
      death reflected apoptotic morphological features, that is, cell membrane
      blebbing, vacuolization, chromatin condensation, and nuclear fragmentation. In
      addition, bauerenol treatment diminished the mitochondrial membrane potential, by
      inducing the efflux of cytochrome c, downregulating the levels of anti-apoptotic
      Bcl-2 as well as upregulating the levels of pro-apoptotic Bax, and inducing
      caspase activation and poly (ADP-ribose) polymerase cleavage. Moreover, bauerenol
      treatment activates p38MAPK and inactivates the anti-apoptotic kinases Akt and
      ERK1/2 through the induction of reactive oxygen species. Furthermore, bauerenol
      mediated S-phase arrest was associated with downregulation of cell cycle-rate
      limiting factor (cyclin D1) and upregulation of cyclin-dependent kinase inhibitor
      p21 and tumor suppressor p53. Interestingly, pre-treatment of cells with reactive
      oxygen species inhibitor and p38 inhibitor significantly decreases bauerenol
      induced cytotoxicity, Bax upregulation, and p38 activation. This study clearly
      states that bauerenol induces cell cycle arrest and apoptosis through the
      reactive oxygen species-dependent p38MAPK activation in HepG2 cancer cells.

PMID- 28443466
TI  - Promoter methylation and gene polymorphism are two independent events in
      regulation of GSTP1 gene expression.
AB  - Breast carcinogenesis is a multistep process, involving both genetic and
      epigenetic modification process of genes, involved in diverse pathways ranging
      from DNA repair to metabolic processes. This study was undertaken to assess the
      role of promoter methylation of GSTP1 gene, a member of glutathione-S-transferase
      family of enzymes, in relation to its expression, polymorphism, and
      clinicopathological parameters. Tissue samples were taken from breast cancer
      patients and paired with their normal adjacent tissues. A total of 51 subjects
      were studied, in which the frequency of promoter methylation in cancerous tissue
      was 37.25% as against 11% in the normal tissues ( p <= 0.001). The
      hypermethylated status of the gene was significantly associated with the loss of
      the protein expression ( r = -0.449, p = 0.001, odds ratio = 7.42, 95% confidence
      interval = 2.05-26.92). Furthermore, when compared with the clinical parameters,
      the significant association was found between the promoter hypermethylation and
      lymph node metastasis ( p <= 0.001), tumor stage ( p = 0.039), tumor grade ( p =
      0.028), estrogen receptor status ( p = 0.018), and progesterone receptor status (
      p = 0.046). Our study is the first of its kind in Kashmiri population, which
      indicates that GSTP1 shows aberrant methylation pattern in the breast cancer with
      the consequent loss in the protein expression. Furthermore, it also shows that
      the gene polymorphism (Ile105Val) at codon 105 is not related to the promoter
      methylation and two are the independent events in breast cancer development.

PMID- 28443467
TI  - Effect of irinotecan on HMGB1, MMP9 expression, cell cycle, and cell growth in
      breast cancer (MCF-7) cells.
AB  - Irinotecan is a natural alkaloid agent widely used in cancer therapy. High
      mobility group protein B1 as a non-histone chromosomal protein plays a
      fundamental role in gene expression and inflammation. In this study, the effect
      of irinotecan on high-mobility group protein B1 and MMP9 content, gene
      expression, cell cycle, and cell growth in human breast cancer cells (MCF-7) was
      investigated. The cells were exposed to various concentrations of irinotecan and
      the viability determined by trypan blue exclusion and 3-(4,5-dimethylthiazal-2
      yl)-2,5-diphenyltetrazolium bromide assays. High-mobility group B proteins were
      extracted from the control and drug-treated cells and analyzed by immunoblot.
      High-mobility group protein B1 and MMP9 messenger RNA expression was studied by
      reverse transcription polymerase chain reaction. The results demonstrated
      reduction of cell viability upon increasing irinotecan concentration, up
      regulated high-mobility group protein B1 gene expression, and down-regulated MMP9
      mRNA. Although the content of high-mobility group protein B1 was decreased in
      chromatin extract upon drug action, no high-mobility group protein B1 release to
      extracellular space was detected by immunoblot analysis. Irinotecan decreased
      H3K9 acetylation and increased poly ADP-ribose polymerase fragmentation to 89 kDa
      and anion superoxide production suggesting induction of apoptosis in these cells.
      Propidium iodide staining of the cells 24 h after the drug treatment revealed
      arrest of the cells in S-phase. From the results, it is concluded that
      overexpression of high-mobility group protein B1 in the presence of irinotecan
      precedes breast cancer cells into apoptosis and in this response the binding of
      irinotecan to chromatin or high-mobility group protein B1 may condense/aggregate
      chromatin, preventing high-mobility group protein B1 release from chromatin.

PMID- 28443468
TI  - Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to
      Paclitaxel through microRNA-30c-mediated MTA1 reduction.
AB  - Non-small-cell lung cancer is one of the most lethal cancers in the worldwide.
      Although Paclitaxel-based combinational therapies have long been used as a
      standard treatment in aggressive non-small-cell lung cancers, Paclitaxel
      resistance emerges as a major clinical problem. It has been demonstrated that
      Curcumin from Curcuma longa as a traditional Chinese medicine can inhibit cancer
      cell proliferation. However, the role of Curcumin in Paclitaxel-resistant non
      small-cell lung cancer cells is not clear. In this study, we investigated the
      effect of Curcumin on the Paclitaxel-resistant non-small-cell lung cancer cells
      and found that Curcumin treatment markedly increased the sensitivity of
      Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel.
      Mechanically, the study revealed that Curcumin could reduce the expression of
      metastasis-associated gene 1 (MTA1) gene through upregulation of microRNA-30c in
      Paclitaxel-resistant non-small-cell lung cancer cells. During the course, MTA1
      reduction sensitized Paclitaxel-resistant non-small-cell lung cancer cells and
      enhanced the effect of Paclitaxel. Taken together, our studies indicate that
      Curcumin increases the sensitivity of Paclitaxel-resistant non-small-cell lung
      cancer cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Curcumin
      might be a potential adjuvant for non-small-cell lung cancer patients during
      Paclitaxel treatment.

PMID- 28443469
TI  - Low NKD1 expression predicts adverse prognosis in cytogenetically normal acute
      myeloid leukemia.
AB  - Dysregulation of NKD1 has been identified in several solid tumors. However, the
      status of NKD1 expression and its clinical implication in acute myeloid leukemia
      remain largely elusive. NKD1 transcript level in bone marrow mononuclear cells
      was detected by real-time quantitative polymerase chain reaction in 126 de novo
      acute myeloid leukemia patients and 30 controls. Clinical significance of NKD1
      expression was obtained by the comparison between the patients with low and high
      NKD1 expression. NKD1 messenger RNA level was significantly decreased in acute
      myeloid leukemia patients compared with controls ( p = 0.019). There were no
      significant differences between patients with low and high NKD1 expression in
      sex, age, peripheral blood cells, bone marrow blasts, French-American
      British/World Health Organization subtypes, and karyotypes/karyotypic
      classifications ( p > 0.05). Although no significant difference was observed in
      complete remission rate between NKD1low and NKD1high patients ( p > 0.05), Kaplan
      Meier analysis revealed that NKD1low patients showed shorter overall survival
      time than NKD1high patients in whole-cohort acute myeloid leukemia, non-M3 acute
      myeloid leukemia, and cytogenetically normal acute myeloid leukemia ( p = 0.014,
      0.063, and 0.020). Multivariate analyses disclosed the low NKD1 expression was an
      independent risk factor in cytogenetically normal acute myeloid leukemia patients
      (hazard ratio = 0.397, p = 0.017). Moreover, the prognostic value of NKD1
      expression was confirmed by gene expression profile data in cytogenetically
      normal acute myeloid leukemia patients ( p = 0.028 and 0.011). NKD1 showed
      significantly increased level after induction chemotherapy achieved complete
      remission in follow-up paired acute myeloid leukemia patients ( p < 0.001). These
      findings indicated that reduced NKD1 expression is associated with unfavorable
      clinical outcome in cytogenetically normal acute myeloid leukemia.

PMID- 28443470
TI  - A multi-target protein of hTERTR-FAM96A presents significant anticancer potent in
      the treatment of hepatocellular carcinoma.
AB  - The abilities to escape apoptosis induced by anticancer drugs are an essential
      factor of carcinogenesis and a hallmark of resistance to cancer therapy. In this
      study, we identified hTERTR-FAM96A (human telomerase reverse transcriptase-family
      with sequence similarity 96 member A) as a new efficient agent for apoptosome
      activating and anti-tumor protein and investigated the potential tumor suppressor
      function in hepatocellular carcinoma. The hTERTR-FAM96A fusion protein was
      constructed by genetic engineering and its anticancer function of hTERTR-FAM96A
      was explored in vitro and in vivo by investigating the possible preclinical
      outcomes. Effects of hTERTR-FAM96A on improvement of apoptotic sensitivity and
      inhibition of migration and invasion were examined in cancer cells and tumors.
      Our results showed that the therapeutic effects of hTERTR-FAM96A were highly
      effective for inhibiting tumor growth and inducing apoptosis of hepatocellular
      carcinoma cells in H22-bearing nude mice. The hTERTR-FAM96A fusion protein could
      specifically bind with Apaf-1 and hTERT, which further induced apoptosis of
      hepatocellular carcinoma cells and improved apoptosis sensitivity. Our results
      indicated that hTERTR-FAM96A treatment enhanced cytotoxic effects by upregulation
      of cytotoxic T lymphocyte responses, interferon-gamma release, and T lymphocyte
      infiltration. In addition, hTERTR-FAM96A led to tumor-specific immunologic
      cytotoxicity through increasing apoptotic body on hepatocellular tumors.
      Furthermore, hTERTR-FAM96A dramatically inhibited tumor growth, reduced death
      rate, and prolonged mice survival in hepatocellular carcinoma mice derived from
      three independent hepatocellular carcinoma mice cohorts compared to control
      groups. In summary, our data suggest that hTERTR-FAM96A may serve as an efficient
      anti-tumor agent for the treatment of hepatocellular carcinoma.

PMID- 28443471
TI  - Suppressing the molecular signaling pathways involved in inflammation and cancer
      in breast cancer cell lines MDA-MB-231 and MCF-7 by miR-590.
AB  - Breast cancer is the most frequent cancer among women worldwide. Tumor immunology
      suggests relationships between the immune system, chronic inflammation, and
      cancer. The immune system may either prevent or promote carcinogenesis. Here, we
      evaluated molecular signaling pathways common in inflammation and cancer and
      detected the microRNAs which play pivotal roles in mediating these pathways.
      Using bioinformatics assays, signaling pathways common in inflammation and
      cancer, and microRNAs mediating these pathways were identified. MiR-590 was
      selected and cloned into the pLenti-III-eGFP vector and transfected into the
      breast cancer cell lines. The expression level of microRNA and the candidate
      genes was evaluated by real-time quantitative reverse transcription polymerase
      chain reaction, and the apoptosis level in transfected cells was measured by
      Annexin V-7AAD assay. The cell migration was tested by real-time quantitative
      reverse transcription polymerase chain reaction for MMP2/MMP9. The expression
      levels of miR-590 and the selected genes (i.e. JAK2, PI3K, MAPK1, and CREB) were
      measured 72 h after transfection. While miR-590 showed an over-expression, the
      genes were significantly down-regulated. A significant increase was observed in
      apoptosis level in both cell lines and MMP2/MMP9 was significantly decreased in
      MDA-MB-231 cells. MiR-590 was selected as a microRNA which triggers and down
      regulates critical genes of signaling pathways similar in cancer and
      inflammation. Following the miR-590 treatment, JAK2, PI3K, MAPK1, and CREB were
      down-regulated and the apoptosis level was increased in breast cancer cell lines.
      Apparently, some microRNAs can be good candidates for novel treatments of cancer.
      Although miR-590 showed good results in this study, further studies are required
      to investigate the role of miR-590 in breast cancer therapy.

PMID- 28443472
TI  - MiR-26a downregulates retinoblastoma in colorectal cancer.
AB  - MicroRNAs are non-coding short RNAs that target the 3' untranslated region of
      messenger RNAs (mRNAs) and lead to their degradation or to translational
      repression. Several microRNAs have been designated as oncomirs, owing to their
      regulating tumor suppressor genes. Interestingly, a few of them have been found
      to target multiple genes whose simultaneous suppression contributes to the
      development of a tumoral phenotype. Here, we have showed that miR-26a is
      overexpressed in colorectal cancer data obtained from TCGA Research Network and
      in human colon cancer pathological specimens; moreover, an orthotopic in vivo
      model of colon cancer showed overexpression of miR-26a, while Rb1 expression
      inversely correlated to miR-26a in TCGA Research Network data, pathological
      samples, and the in vivo model. Then, by means of luciferase assay, we
      demonstrated that miR-26a targets the 3' untranslated region of Rb1 mRNA
      directly. This is, to our knowledge, the first report of miR-26a targeting Rb1 in
      colon cancer. The results of this study suggested that miR-26a could serve as a
      progression biomarker in colorectal cancer. Further validation studies are still
      needed to confirm our findings.

PMID- 28443473
TI  - Proteomic identification of potential biomarkers for cervical squamous cell
      carcinoma and human papillomavirus infection.
AB  - It is known that high-risk human papillomavirus infection is the main etiological
      factor in cervical carcinogenesis. However, human papillomavirus screening is not
      sufficient for early diagnosis. In this study, we aimed to identify potential
      biomarkers common to cervical carcinoma and human papillomavirus infection by
      proteomics for human papillomavirus-based early diagnosis and prognosis. To this
      end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin
      embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical
      intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han
      women. Human papillomavirus infection by eight oncogenic human papillomavirus
      types was detected in tissue DNA samples using a quantitative polymerase chain
      reaction. The protein profile of cervical specimens from human papillomavirus 16
      positive squamous cell carcinoma and human papillomavirus-negative normal
      controls was analyzed by proteomics and bioinformatics. The expression of
      candidate proteins was further determined by quantitative reverse transcriptase
      polymerase chain reaction and immunohistochemistry. We identified 67 proteins
      that were differentially expressed in human papillomavirus 16-positive squamous
      cell carcinoma compared to normal cervix. The quantitative reverse transcriptase
      polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2,
      DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma
      compared to normal cervix ( p < 0.05). In addition, the transcription of PCBP2,
      MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical
      intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry
      staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5
      in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared
      to normal controls ( p < 0.05). Our data suggest that the expression of ASAH1,
      PCBP2, DDX5, and hnRNPA1, and possibly MCM4, MCM5, CYC, ENO1, and TYPH, is
      upregulated during cervical carcinogenesis and potentially associated with human
      papillomavirus infection. Further validation studies of the profile will
      contribute to establishing auxiliary diagnostic markers for human papillomavirus
      based cancer prognosis.

PMID- 28443474
TI  - ATP citrate lyase is increased in human breast cancer, depletion of which
      promotes apoptosis.
AB  - Breast cancer is a malignant tumor that is harmful to women's health around the
      world. Investigating the biological mechanism is, therefore, of pivotal
      importance to improve patients' prognoses. Compared to non-neoplastic tissues,
      enhanced glucose and lipid metabolism is one of the most common properties of
      malignant breast cancer. Adenosine triphosphate (ATP) citrate lyase is a key
      enzyme linking aerobic glycolysis and fatty acid synthesis and is of high
      biological and prognostic significance in breast cancer. In our clinical study,
      fresh clinical tissues were used to analyze ATP citrate lyase expression by
      western blotting, and paraffin archived samples from 62 breast cancer patients
      were used to analyze ATP citrate lyase expression by immunohistochemistry. In the
      cellular study, following small interfering RNA-mediated inhibition of ATP
      citrate lyase in MCF-7 cells, cell viability and apoptosis were measured using
      the Cell Counting Kit-8 and flow cytometry, respectively. Breast cancer tissues
      showed strong expression of ATP citrate lyase, whereas adjacent normal tissues
      showed weak expression. Silencing of endogenous ATP citrate lyase expression by
      small interfering RNA in MCF-7 cells suppressed cell viability and increased cell
      apoptosis. Collectively, our study revealed that expression of ATP citrate lyase
      was significantly increased in breast cancer tissue compared with normal tissue.
      In addition, we found that depletion of ATP citrate lyase suppressed tumor
      growth, which suggests that ATP citrate lyase-related inhibitors might be
      potential therapeutic approaches for breast cancer.

PMID- 28443475
TI  - MicroRNA-140-5p inhibits cell proliferation and invasion by regulating VEGFA/MMP2
      signaling in glioma.
AB  - Glioma is the most common primary malignant tumor of the central nervous system,
      which results in both a poor prognosis and outcome because of the aggressive
      progression of disease, growth and resistance to surgery, chemotherapy, and
      radiotherapy. MiR-140-5p is a small, non-coding single-stranded RNA molecule,
      which was previously studied in the settings of human tongue cancer,
      hepatocellular carcinoma, and colorectal cancer. However, detailed data that
      formally demonstrate the contribution of miR-140-5p to glioma development are
      missing. Similarly, relatively little is known about the relationship of miR-140
      5p, vascular endothelial growth factor A, and matrix metalloproteinase-2 in
      glioma progression. In this study, we found that miR-140-5p expression was
      significantly decreased in glioma tissues and in the glioma cell-lines U87 and
      U251 as compared with non-cancerous brain tissues by quantitative real-time
      polymerase chain reaction. In addition, miR-140-5p inhibited glioma cell
      proliferation and invasion and promoted glioma cell apoptosis both in vivo and in
      vitro. Interestingly, while the expression levels of miR-140-5p were higher in
      glioma cells, the messenger RNA or protein expression levels of vascular
      endothelial growth factor A and matrix metalloproteinase-2 were lower in glioma
      cells as determined by quantitative real-time polymerase chain reaction, western
      blot assay, and immunohistochemistry. By contrast, downregulation in the
      expression levels of miR-140-5p augmented the messenger RNA and protein
      expression levels of both vascular endothelial growth factor A and matrix
      metalloproteinase-2. These findings suggested that miR-140-5p inhibited glioma
      proliferation and invasion by regulating the vascular endothelial growth factor
      A/matrix metalloproteinase-2 signaling pathway both in vitro and in vivo.

PMID- 28443476
TI  - Knocking down glycoprotein nonmetastatic melanoma protein B suppresses the
      proliferation, migration, and invasion in bladder cancer cells.
AB  - Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein
      that has been recently found to play a role in cancer cell proliferation,
      angiogenesis, and invasion. Due to its potential responsibility in cancer
      aggressiveness, the main objective of this work was to investigate its expression
      in bladder cancer and the biological functions in bladder cancer cells. Using
      immunohistochemistry, western blot, and reverse transcription polymerase chain
      reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma
      protein B in bladder cancer tissues and bladder cancer cell lines. The effects of
      glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and
      invasion were tested after knocking down the glycoprotein nonmetastatic melanoma
      protein B in bladder cancer cells with small interfering RNAs by CCK-8,
      Transwell, and Matrigel assays. Our results showed that glycoprotein
      nonmetastatic melanoma protein B protein was highly expressed in the bladder
      cancer tissues and cell lines. Downregulating glycoprotein nonmetastatic melanoma
      protein B could suppress the proliferation, migration, and invasion in bladder
      cancer cells. Glycoprotein nonmetastatic melanoma protein B expression was
      related to the poor differentiation and recurrence by immunohistochemistry
      analysis. The survival analysis also showed that glycoprotein nonmetastatic
      melanoma protein B was related to the patient prognosis. In conclusion,
      Glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the
      bladder cancer, which was related to the poor prognosis in bladder cancer
      patients. Glycoprotein nonmetastatic melanoma protein B promoted the
      proliferation, migration, and invasion in bladder cancer cells.

PMID- 28443477
TI  - Psychotherapist trainees' professional self-doubt and negative personal reaction:
      Changes during cognitive behavioral therapy and association with patient
      progress.
AB  - OBJECTIVE: This study examined psychotherapist trainees' experiences of
      "professional self-doubt" (PSD) and "negative personal reaction" (NPR) during
      cognitive behavioral therapy (CBT) and their associations with patients' symptoms
      and interpersonal problems. METHOD: Forty therapists treating 621 patients were
      analyzed. Patients' symptoms and interpersonal problems were collected repeatedly
      during therapy. Data about patients' interpersonal problems were available only
      for 106 patients and 18 therapists. Therapists' difficulties were assessed as
      trait-based (one assessment across all patients) and as state-based (repeated
      assessments for each individual patient) difficulties. Multilevel models were
      performed. RESULTS: None of the trait-based difficulties correlated with the
      change of the patients' symptoms. Yet, more NPR at the trait-level predicted a
      more favorable change, whereas higher PSD at the trait-level showed an opposite
      effect on change of patients' interpersonal problems. Regarding state-based
      difficulties, PSD as well as NPR decreased significantly over the course of CBT.
      Patients whose therapists' experienced PSD to increase during CBT were at risk of
      a less favorable patient progress regarding symptoms, whereas the change of
      interpersonal problems was not significantly associated with changes in
      therapists' difficulties. CONCLUSION: Patients' progress is associated with
      therapists' experiences of difficulties. Yet, trait- and state-based difficulties
      lead to different results. Clinical or methodological significance of this
      article: Associations between therapists' difficulties and patient-reported
      outcomes depended on whether therapists' difficulties were assessed once across
      all patients (trait-level) or for each individual patient repeatedly during CBT
      (state-level). Contrary to previous research on trait-level difficulties, the
      difficulty professional self-doubt (PSD) was associated with a less favorable
      course of patients' interpersonal problems, whereas the difficulty negative
      personal reaction (NPR) was associated with a more favorable progress. Moreover a
      patient-therapist-time contextualization (state-level) seems relevant for the
      assessment of complex therapist variables and an elaborated understanding of the
      therapist effect. Altogether, CBT trainees should not be scared of their negative
      personal reactions towards their patients and professional self-doubt of CBT
      trainees should be monitored and discussed (e. g., in supervision).

PMID- 28443478
TI  - Role of Oxidative Stress in Epigenetic Modification in Endometriosis.
AB  - Aberrant DNA methylation and histone modification are associated with an
      increased risk of reproductive disorders such as endometriosis. However, a cause
      effect relationship between epigenetic mechanisms and endometriosis development
      has not been fully determined. This review provides current information based on
      oxidative stress in epigenetic modification in endometriosis. This article
      reviews the English-language literature on epigenetics, DNA methylation, histone
      modification, and oxidative stress associated with endometriosis in an effort to
      identify epigenetic modification that causes a predisposition to endometriosis.
      Oxidative stress, secondary to the influx of hemoglobin, heme, and iron during
      retrograde menstruation, is involved in the expression of CpG demethylases, ten
      eleven translocation, and jumonji (JMJ). Ten-eleven translocation and JMJ
      recognize a wide range of endogenous DNA methyltransferases (DNMTs). The
      increased expression levels of DNMTs may be involved in the subsequent
      downregulation of the decidualization-related genes. This review supports the
      hypothesis that there are at least 2 distinct phases of epigenetic modification
      in endometriosis: the initial wave of iron-induced oxidative stress would be
      followed by the second big wave of epigenetic modulation of endometriosis
      susceptibility genes. We summarize the recent advances in our understanding of
      the underlying epigenetic mechanisms focusing on oxidative stress in
      endometriosis.

PMID- 28443479
TI  - Melatonin Improves Mitochondrial Respiration in Syncytiotrophoblasts From
      Placentas of Obese Women.
AB  - Maternal obesity is associated with increased oxidative stress but decreased
      placental mitochondrial respiration and expression of mitochondrial electron
      transport chain (ETC) complexes I to V. Melatonin acts as an antioxidant and
      prevents oxidative stress-induced changes in cytotrophoblasts. Placentas were
      collected at term by cesarean delivery from obese (first trimester body mass
      index [BMI] >=30, n = 10) or lean (BMI < 25, n = 6) women. Cytotrophoblasts were
      isolated and allowed to syncytialize for 72 hours with or without melatonin (0.1
      100 uM) for the last 24 hours. Mitochondrial respiratory parameters were measured
      in a Seahorse XF24. Expression of ETC complexes I to V and antioxidant enzymes
      was measured by Western blot. Maternal clinical characteristics of patients were
      similar except for BMI. No significant improvement in mitochondrial respiration
      occurred with addition of melatonin to trophoblasts of lean women. However, in
      trophoblasts from obese women, melatonin (10 and 100 umol/L) significantly
      increased maximal respiration ( P = .01 and P = .009, respectively) and spare
      capacity ( P = .02 and P = .003, respectively) compared to the untreated control.
      No differences were detected in the expression of ETC complexes and superoxide
      dismutase 1 or 2 in trophoblasts treated with melatonin. The expression of
      glutathione peroxidase, which was significantly greater in trophoblast of obese
      compared to lean women ( P < .05), was decreased back to the level seen in
      trophoblast of lean women with addition of melatonin ( P = .02). Improved spare
      respiratory capacity, the cellular reserve, could impart a protective effect to
      the placenta and fetus in an adverse intrauterine environment or in response to
      additional stressors.

PMID- 28443480
TI  - Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate
      Model of Gestational Protein Restriction.
AB  - Maternal malnutrition during pregnancy impacts fetal growth, with developmental
      consequences that extend to later life outcomes. In underdeveloped countries,
      this malnutrition typically takes the form of poor dietary protein content and
      quality, even if adequate calories are consumed. Here, we report the
      establishment of a nonhuman primate model of gestational protein restriction (PR)
      in order to understand how placental function and pregnancy outcomes are affected
      by protein deficiency. Rhesus macaques were assigned to either a control diet
      containing 26% protein or switched to a 13% PR diet prior to conception and
      maintained on this PR diet throughout pregnancy. Standard fetal biometry, Doppler
      ultrasound of uteroplacental blood flow, ultrasound-guided amniocentesis, and
      contrast-enhanced ultrasound (CE-US) to assess placental perfusion were performed
      mid-gestation (gestational day 85 [G85] where term is G168) and in the early
      third trimester (G135). Our data demonstrate that a 50% reduction in dietary
      protein throughout gestation results in reduced placental perfusion, fetal growth
      restriction, and a 50% rate of pregnancy loss. In addition, we demonstrate
      reduced total protein content and evidence of fetal hypoxia in the amniotic
      fluid. This report highlights the use of CE-US for in vivo assessment of
      placental vascular function. The ability to detect placental dysfunction, and
      thus a compromised pregnancy, early in gestation, may facilitate the development
      of interventional strategies to optimize clinical care and improve long-term
      offspring outcomes, which are future areas of study in this new model.

PMID- 28443481
TI  - Impact of Abnormal DNA Methylation of Imprinted Loci on Human Spontaneous
      Abortion.
AB  - Currently, there is a growing concern regarding the safety of assisted
      reproductive technology (ART) due to increased risk of spontaneous abortion (SA)
      and imprinting disorders in ART-conceived offspring. Early investigations
      suggested that aberrant genetic imprinting may be related to pregnancy loss;
      however, few studies have used human tissue specimens. Here the DNA methylation
      patterns of 3 imprinted genes, including maternally inherited GRB10 and the
      paternally inherited IGF2 and PEG3 genes, were evaluated in human chorionic
      villus samples by pyrosequencing and bisulfite sequencing polymerase chain
      reaction. The samples were divided into 4 groups: (1) SA of natural conception
      (NC; n = 84), (2) induced abortion of NC (n = 94), (3) SA after ART (n = 73), and
      (4) fetal reduction after ART (n = 86). The methylation levels and the
      percentages of abnormal methylation of the IGF2, GRB10, and PEG3 genes between
      the ART group and the NC group showed no significant difference. Both IGF2 and
      GRB10 genes showed higher methylation levels in the SA group compared to the non
      SA group. Additionally, determining the single-nucleotide polymorphisms of 4
      loci, including IGF2 rs3741205, rs3741206, rs3741211, and GRB10 rs2237457, showed
      that the TC+CC genotype of IGF2 rs3741211 had a 1.91-fold increased risk of SA
      after ART. However, there was no association between the mutant genotype of IGF2
      rs3741211 and the methylation levels of IGF2 and H19, and ART might not affect
      the distribution of the abovementioned genotypes. It provides support for the
      opinion that genetic imprinting defects may be associated with SA, which might
      not be due to ART treatments.

PMID- 28443482
TI  - Subarachnoid and intraperitoneal hemorrhage secondary to segmental arterial
      mediolysis: A case report and review of the literature.
AB  - Background Segmental arterial mediolysis (SAM) is an uncommon or underdiagnosed
      arteriopathy that presents with life-threatening hemorrhage. SAM can affect the
      intracranial, spinal, and visceral arteries, with reported cases of concomitant
      intracranial and visceral hemorrhage. Case description We present the case of a
      61-year-old male with concurrent subarachnoid and intraperitoneal hemorrhage
      caused by simultaneously bleeding posterior spinal artery and splenic artery
      pseudoaneurysms. The posterior spinal artery pseudoaneurysms were treated with
      selective injection of polyvinyl alcohol particles into the posterior spinal
      artery, while the splenic artery pseudoaneurysm was treated with Gelfoam
      embolization. The constellation of imaging, clinical, and laboratory features led
      to a presumptive diagnosis of SAM, which remains the only reported cause of
      concurrent neurovascular and visceral artery aneurysm rupture. Conclusion SAM is
      a key diagnostic consideration in cases of concomitant intracranial, spinal, and
      visceral artery aneurysm rupture.

PMID- 28443483
TI  - Aneurysm size and the Windkessel effect: An analysis of contrast intensity in
      digital subtraction angiography.
AB  - Large cerebral aneurysms are considered more dangerous than their smaller
      counterparts, with higher risk of subarachnoid hemorrhage. Understanding the
      hemodynamics of large aneurysms has potential to predict their response to
      treatment. Digital subtraction angiography images for patients with intracranial
      aneurysms over a seven-year period were reviewed. Unruptured solitary aneurysms
      of the internal carotid artery (ICA) proximal to the terminus and posterior
      communicating artery were included. Contrast intensity over time was analyzed at
      the center of the M1 segment of the middle cerebral artery distal to the aneurysm
      and compared to the contralateral side. Analysis included time to peak (TP)10%
      100% (time needed for contrast to change from 10% intensity to 100%), washout
      time (WT)100%-10% (time for 100% intensity to 10%), and quartile time (QT)25%-25%
      (time for 25% intensity during vessel filling to 25% during emptying). Fifty
      patients met the inclusion criteria. Analysis over the ipsilateral M1 segment
      revealed a significant increase in QT25%-25% (8.5 vs 7.6 seconds, p = 0.006)
      compared to the contralateral side. There was a correlation between TP10%-100%
      and QT25%-25% with aneurysm size (Pearson's r = 0.37, p = 0.007 and r = 0.43, p =
      0.001, respectively). Larger ICA aneurysms were associated with delayed contrast
      intensity times . A plausible mechanism is that large aneurysms act as a
      capacitance chamber (Windkessel effect) that slow the arrival of contrast distal
      to the aneurysm. This may be of significance for large aneurysms after treatment,
      where the loss of the Windkessel effect places the distal circulation at greater
      risk for hemorrhage, and warrants further study.

PMID- 28443484
TI  - Manual aspiration thrombectomy with a Penumbra catheter for acute anterior
      cerebral artery occlusion.
AB  - Purpose The purpose of this article is to assess the efficacy and safety of
      manual aspiration thrombectomy (MAT) using a Penumbra catheter in patients with
      anterior cerebral artery (ACA) occlusions. Materials and methods From January
      2012 to March 2016, 16 patients underwent MAT with Penumbra catheters using a
      proximal and distal supporting technique to treat ACA occlusions. We evaluated
      immediate angiographic results and clinical outcomes by reviewing patient
      electrical medical records. Results Of these patients, 11 had a complete
      obstruction of the distal internal carotid artery (ICA) and five had ACA and
      middle cerebral artery (MCA) occlusions. All patients achieved successful
      recanalization of the distal ICA or MCA (Thrombolysis in Cerebral Infarction
      (TICI) grade >=2b). Overall the recanalization rate for ACA occlusions (TICI
      grade>=2b) was 93.7% (15/16). The median procedure time was 45 minutes (range: 35
      65 minutes). No patients were observed to have a procedure-related subarachnoid
      hemorrhage. Four patients (25.0%) died during hospitalization because of massive
      symptomatic hemorrhage, brain edema, or herniation. At discharge, the median
      NIHSS score for surviving patients was 6 (range: 1-17). Five patients had
      favorable clinical outcomes (modified Rankin scale <=2). Conclusion MAT appears
      to be safe and successfully achieves recanalization in patients with ACA
      occlusions.

PMID- 28443485
TI  - Letter regarding article "Quantitative assessment of parent vessel and distal
      intracranial hemodynamics following pipeline flow diversion".

PMID- 28443486
TI  - Repeated lifestyle interventions lead to progressive weight loss: A retrospective
      review chart study.
AB  - AIMS: This study aimed to investigate whether repeated lifestyle interventions
      lead to progressive weight loss or to weight cycling. METHODS: A retrospective
      review chart study with follow-up on 2120 participants (mean+/-SD age 36+/-15
      years; body weight 116+/-28 kg; fat 43+/-6%). All had participated in one to four
      11-12 week lifestyle interventions (residential weight loss programme, mixed
      activities). Weight loss was promoted through a hypocaloric diet (-500 to -700
      kcal/day) and daily physical activity (1-3 hours/day). Primary outcomes were
      weight loss and change in body composition (bioimpedance measurements) after the
      intervention periods and at follow-up. RESULTS: A total of 2120, 526, 139 and 47
      people participated in one to four interventions with mean+/-SEM times from start
      to follow-up of 1.3+/-0.1, 2.9+/-0.2, 4.2+/-0.3 and 5.2+/-0.4 years respectively.
      Overall 50, 41, 18 and 11% of the participants were lost to follow-up after one
      to four interventions, respectively. The cumulated weight loss at follow-up
      increased with the number of interventions from one to four: 12.2+/-0.1, 15.9+/
      0.7, 16.1+/-1.2 and 18.5+/-2.0 kg ( p<0.001). The ratios between cumulated loss
      of fat and fat free mass after one to four interventions decreased with the
      number of interventions (2.4, 2.2, 2.1 and 1.4). Rates of weight loss during the
      interventions ranged from 0.70+/-0.06 to 1.06+/-0.01 kg/week and the maximum
      weight regain during the follow-up periods was 0.039+/-0.007 kg/week.
      CONCLUSIONS: Repeated relatively short lifestyle interventions in a selected and
      motivated group can be an efficient method for weight loss maintenance with only
      limited body weight cycling in the interim periods. However, the relationship
      between loss of fat and fat free mass might change in an unfavourable direction.

PMID- 28443487
TI  - Objectively measured physical activity and 12-month trajectories of neck-shoulder
      pain in workers: A prospective study in DPHACTO.
AB  - AIMS: This study aimed to investigate the association between objectively
      measured physical activity at work and leisure and the intensity (mean level and
      time course) of neck-shoulder pain (NSP) over 12 months among male and female
      blue collar workers. METHODS: Data were obtained from 625 blue collar workers
      from the Danish cohort DPHACTO. Physical activity was measured objectively at
      baseline using accelerometers. The percentage of time spent in physical activity
      (walking, climbing stairs, running and cycling) was calculated for both work and
      leisure time. Longitudinal data on the intensity of NSP (numerical rating scale 0
      10) were collected using text messages every fourth week over 12 months. Linear
      mixed models were used to investigate the associations between occupational
      physical activity (OPA) and leisure time physical activity (LTPA) and the
      trajectories of the intensity of NSP, adjusted for individual, biomechanical and
      psychosocial factors, and baseline pain. RESULTS: OPA was not associated with the
      mean intensity of NSP over 12 months. LTPA was negatively associated with the
      mean intensity of NSP both among men ( B=-0.71, 95% CI -1.31 to -0.11) and women
      ( B=-0.85, 95% CI -1.57 to -0.13). Sex interactions on the 12-month trajectories
      of NSP showed that higher physical activity was associated with a slower
      reduction in NSP among men for OPA only ( B=0.03, 95% CI 0.01-0.05) and women for
      LTPA only ( B=0.05, 95% CI 0.00-0.09). CONCLUSIONS: We found that more time in
      LTPA was associated with a lower overall intensity of NSP over 12 months among
      blue collar workers. However, depending on sex and domain, high physical activity
      had an unfavourable effect on the course of NSP over 12 months.

PMID- 28443488
TI  - Socioeconomic status, social capital and self-reported unmet health care needs: A
      population-based study.
AB  - AIMS: The aim of this study was to investigate the associations between
      socioeconomic status (SES) and self-reported unmet health care needs, taking
      economic stress, generalized trust in other people and trust in the health care
      system into account. METHODS: The 2012 public health survey in Scania was
      conducted using a postal questionnaire and included 28,029 participants aged 18
      80 years. The study was cross-sectional. Associations between SES and unmet
      health care needs were investigated, adjusting for economic stress and trust in
      logistic regressions. RESULTS: SES was significantly associated with unmet health
      care needs. The SES categories of unemployed, on long-term sick leave and
      unskilled manual workers reported particularly high levels of unmet health care
      needs. SES differences in unmet needs were attenuated when economic stress and
      the two dimensions of trust and self-rated health were introduced in multiple
      analyses. The working population gave a lack of time as the reason for unmet
      health care needs, whereas those on sick leave or unemployed reported a lack of
      money. CONCLUSIONS: SES differences in self-reported unmet health care needs were
      observed and these associations were attenuated when economic stress during the
      past year, generalized trust in other people, trust in the health care system and
      self-rated health were introduced into the multiple models.

PMID- 28443489
TI  - Relationship between volition, physical activity and weight loss maintenance:
      Study rationale, design, methods and baseline characteristics.
AB  - AIMS: To investigate the relationship between volition, physical activity and
      weight loss maintenance. METHODS: We recruited 84 sedentary (maximal oxygen
      uptake: 25 +/- 5 ml/min), overweight and obese (Body mass index (BMI) 38 +/- 7
      m/h2, fat 44 +/- 7 %) women ( n = 55) and men ( n = 29) for an interdisciplinary
      prospective study with follow-up. The change in lifestyle and weight loss is
      promoted via a 3-month intensive lifestyle intervention at a private health
      school. The intervention consists of supervised training (1-3 hours/day), a
      healthy hypo-caloric diet (-500 to -700 kCal/day) and education in healthy
      lifestyle in classes/groups. The participants' body weight and composition (Dual
      Energy X-ray absorptiometry), volitional skills (questionnaire), physical
      activity level (heart rate accelerometer/questionnaire) and maximal oxygen uptake
      (indirect calorimetry) are to be monitored before, after, and 3 and 12 months
      after the intervention. RESULTS: At the 12-month follow-up, three different
      groups will be established: Clinical weight loss maintenance (> 10% weight loss
      from baseline), moderate weight loss maintenance (1-10% weight loss) and no
      weight loss (or weight regain). A linear mixed model analysis will be used to
      compare levels of volitional skills, physical activity and maximal oxygen uptake
      over time, between the three groups. Correlational analyses will be used to
      investigate possible associations between volition, maximal oxygen uptake,
      physical activity level and weight loss maintenance. CONCLUSIONS: If specific
      volitional skills are identified as predictors of adherence to physical activity
      and success in clinical weight loss maintenance, these can be trained in future
      intensive lifestyle interventions in order to optimize the success rate.

PMID- 28443490
TI  - Waiting times for cancer patients in Sweden: A nationwide population-based study.
AB  - AIMS: The reported long waiting times for cancer patients have mostly been
      related to prognostic outcome and less to patient-related experience to outcome.
      We assessed waiting times for patients with cancer of the breast, prostate, colon
      or rectum in Sweden. METHODS: The median time from referral to start of treatment
      was assessed using data from clinical cancer registers for patients who received
      curative treatment during 2011, 2012 and 2013. RESULTS: The median overall
      waiting time in different counties ranged from 7 to 28 days for breast cancer,
      from 117 to 280 days for prostate cancer, from 27 to 64 days for colon cancer and
      from 48 to 80 days for rectal cancer. For the entire nation, the median time from
      referral to start of treatment remained unchanged from 2011 to 2013 for each
      cancer diagnosis. CONCLUSIONS: Large variations were found in waiting times
      between different counties in Sweden and between different types of cancer. The
      long waiting times identified in this study emphasize the need to improve
      national programmes for more rapid diagnosis and treatment.

PMID- 28443491
TI  - Days of sick leave and inpatient care at the time of pregnancy and childbirth in
      relation to maternal age.
AB  - AIMS: To explore whether older women differ from younger women with respect to
      sick leave and inpatient care at the time around their first pregnancy and
      delivery. METHODS: This was a descriptive population-based cohort study. The
      study population included all 236,176 nulliparous women registered as living in
      Sweden who gave birth to their first singleton infant in 2006-2010. Data from
      nationwide Swedish registers were used. Maternal age was categorized in five-year
      intervals. Time was calculated in years with the delivery date as the starting
      point, from two years before and up to three years after delivery. Descriptive
      statistics were used to calculate mean values and ANOVA tables were used to
      obtain the 95% confidence intervals of the means. Restriction was used to reduce
      potential confounding. RESULTS: Women aged ?35 years had a higher annual mean
      number of sick leave days from two years before to one year after their delivery
      date compared with younger women. The range for all age categories in the year
      before the delivery date, including pregnancy, was 15.3-37.4 mean sick leave
      days. The mean number of inpatient days increased with each age category during
      the year after the date of delivery in the range 1.4-4.3 days. CONCLUSIONS: This
      first explorative study indicates the need for more knowledge on morbidity among
      older primiparous women. They had a higher number of days with sick leave and
      hospitalization in the year before and after their delivery date. This might
      reflect higher health risks during pregnancy and childbirth among older women;
      however, social factors and reverse causation might also be influential.

PMID- 28443492
TI  - Consumption of healthy foods and associated socio-demographic factors among
      Russian, Somali and Kurdish immigrants in Finland.
AB  - AIMS: We evaluated the consumption of healthy foods among Russian, Somali and
      Kurdish immigrants in Finland, and examined the relationship between socio
      demographic factors and food consumption. METHODS: We used data from the Migrant
      Health and Wellbeing Study (Maamu), a population-based health interview and
      examination survey in six different municipalities in Finland between 2010 and
      2012. Altogether, 635 men and 737 women, aged 18-64 years, of Russian ( n = 527),
      Somali ( n = 337) and Kurdish ( n = 508) origin were included. The important
      socio-demographic determinants of healthy food consumption - sex, age, education,
      place of residence and household size - were assessed by logistic regression.
      RESULTS: Based on the consumption frequencies of recommended healthy foods -
      fruits, berries, vegetables, fish and rye bread - immigrants of Russian origin
      had higher consumption of healthy foods than their peers of Kurdish and Somali
      origin. Low consumption of fresh vegetables, fruits and berries was found among
      Somali immigrants. Sex and age were the most important determinants of healthy
      food consumption, as women and older age groups had diets closer to the national
      nutrition recommendations. High educational level was also positively associated
      with healthy food consumption. CONCLUSIONS: We found ethnic differences in the
      consumption of healthy foods among the immigrant groups of Russian, Somali and
      Kurdish origin in Finland. Socio-demographic factors, especially age, sex and
      education, seem to also play an important role in immigrants' food consumption.
      Further studies examining the consumption of fruits, berries and fresh vegetables
      among Somali immigrants in Finland are needed.

PMID- 28443493
TI  - Pre-pregnancy body mass index and inter-pregnancy weight change among women of
      Russian, Somali and Kurdish origin and the general Finnish population.
AB  - OBJECTIVES: We studied the differences in the mean pre-pregnancy body mass index
      (BMI) and mean inter-pregnancy weight change in women of Russian, Somali and
      Kurdish origin and women in the general Finnish population. METHODS: The
      population-based samples were from the Migrant Health and Wellbeing Study and the
      Health 2011 Survey conducted in six cities in Finland in 2010-2012. This study
      included women with at least one birth in Finland. Data on their previous
      pregnancies in Finland were obtained from the National Medical Birth Register for
      318 Russian, 584 Somali and 373 Kurdish origin women and for 243 women in the
      general Finnish population (reference group). Data on pre-pregnancy weight and
      height were self-reported in early pregnancy. Linear logistic regression was the
      main method of analysis. RESULTS: The unadjusted mean pre-pregnancy BMI was
      higher in Somali (27.0 kg/m2, p<0.001) and Kurdish (25.8 kg/m2, p<0.001) women,
      but lower in Russian (22.2 kg/m2, p<0.001) women than in the reference group
      (24.1 kg/m2). The adjusted coefficients for the difference in the mean pre
      pregnancy BMI were -1.93 (95% CI -2.77 to -1.09) for Russian, 1.82 (95% CI 0.89
      2.75) for Somali and 1.30 (95% CI 0.43-2.17) for Kurdish women compared with the
      reference group. Among women with at least two births, no statistically
      significant difference was observed in the mean inter-pregnancy weight change
      between the migrant groups and the reference group. CONCLUSIONS: Somali and
      Kurdish women had higher mean pre-pregnancy BMIs than women in the general
      Finnish population and may need special support and health promotion strategies
      for weight management.

PMID- 28443494
TI  - Expression profiling of long non-coding RNA identifies linc-RoR as a prognostic
      biomarker in oral cancer.
AB  - Oral squamous cell carcinoma is the most aggressive cancer that is associated
      with high recurrence, metastasis, and poor treatment outcome. Dysregulation of
      long non-coding RNAs has been shown to promote tumor growth and metastasis in
      several cancers. In this study, we investigated the expression of 11 selected
      long non-coding RNAs that are associated with cell proliferation, metastasis, and
      tumor suppression in oral squamous cell carcinomas and normal tissues by
      quantitative real-time polymerase chain reaction. Out of the 11 long non-coding
      RNAs profiled, 9 were significantly overexpressed in tumors with tobacco chewing
      history. Moreover, the long non-coding RNA profile was similar to the head and
      neck cancer datasets of The Cancer Genome Atlas database. Linc-RoR, a regulator
      of reprogramming, implicated in tumorigenesis was found to be overexpressed in
      undifferentiated tumors and showed strong association with tumor recurrence and
      poor therapeutic response. In oral squamous cell carcinomas, for the first time,
      we observed linc-RoR overexpression, downregulation of miR-145-5p, and
      overexpression of c-Myc, Klf4, Oct4, and Sox2, suggesting the existence of linc
      RoR-mediated competing endogenous RNA network in undifferentiated tumors. Taken
      together, this study demonstrated the association of linc-RoR overexpression in
      undifferentiated oral tumors and its prognostic value to predict the therapeutic
      response.

PMID- 28443495
TI  - ALDH1A3 correlates with luminal phenotype in prostate cancer.
AB  - Prostate cancer is the most common male malignancies in the United States. The
      specific characteristics of different disease stages have been deeply
      investigated. We present our data on ALDH1A3 as a potential therapeutic target
      for the prostate cancer based on several functional investigations. Also, we used
      The Cancer Genome Atlas datasets for primary prostate cancer to detect the
      relevance of ALDH1A3 and prostate cancer luminal phenotype. We found that ALDH1A3
      correlated with androgen receptor signaling pathway in primary prostate cancer,
      which is consistent with its luminal layer localization. Then, from the genetic
      manipulation assay, we knocked out the ALDH1A3 in PC-3 cells and found
      significantly reduced proliferation rate as well as the invasion ability.
      Furthermore, we looked up our single center primary prostate cancer post
      operative follow-up data and suggested that the high level ALDH1A3 expression
      could predict the poor progression-free survival in a 158-patient cohort. We
      concluded that ALDH1A3, localized in luminal layer in prostate epithelium, is
      highly expressed in prostate cancer. It played important role in maintaining the
      proliferation, invasion, and cell cycle. It can also become the potential
      biomarker in the future to guide the therapeutic manipulations for primary
      prostate cancer.

PMID- 28443496
TI  - A novel epidermal growth factor receptor inhibitor for treating lung cancer.
AB  - To investigate the effects of a novel synthetic epidermal growth factor receptor
      inhibitor, COMPOUND7809, on the inhibition of lung cancer growth in vitro and the
      underlying mechanisms, we treated three lung tumor cell lines (A549, SK-LU-1, and
      NCI-H23) with COMPOUND7809 and a Food and Drug Administration-approved epidermal
      growth factor receptor inhibitor gefitinib. Then, we examined cell growth in a 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell survival
      in a Cell Counting Kit-8 assay, and cell apoptosis by Annexin V flow cytometry in
      the presence of fluorouracil. We found that compared to gefitinib, COMPOUND7809
      inhibited cell growth more potentially and induced more cell death in the
      presence of fluorouracil. Thus, our study demonstrates that COMPOUND7809 may be a
      promising epidermal growth factor receptor inhibitor for human lung cancer
      therapy.

PMID- 28443497
TI  - Netrin-1 in cancer: Potential biomarker and therapeutic target?
AB  - Netrin-1, a laminin-related protein, is known to be involved in the nervous
      system development. Recently, Netrin-1's involvement in other processes such as
      cell adhesion, motility, proliferation, and differentiation that are important
      for the development of epithelial tissues has been described. In addition, Netrin
      1 and its receptors, deleted in colorectal cancer and uncoordinated-5 homolog,
      have been linked to apoptosis and angiogenesis. Since these properties are
      essential for tumor development, Netrin-1 and its receptors have been reported to
      promote tumorigenesis in many types of cancers. Here, we review the Netrin-1
      mediated regulation of cancer, its potential use as a biomarker, and the
      targeting of the Netrin-1 pathway to treat cancers.

PMID- 28443498
TI  - The overexpression of Rabl3 is associated with pathogenesis and clinicopathologic
      variables in hepatocellular carcinoma.
AB  - Overexpression of Rabl3 is associated with some malignancies. However, their
      relationship with hepatocellular carcinoma remains unclear. In this study, the
      expression of Rabl3 in hepatocellular carcinoma cell lines, and four pairs of
      matched hepatocellular carcinoma tissues and their adjacent normal hepatic
      tissues were detected by quantitative reverse transcription polymerase chain
      reaction and western blot. In addition, the protein expression of Rabl3 was
      examined in 162 cases of hepatocellular carcinoma by immunohistochemistry. Rabl3
      in hepatocellular carcinoma cell lines was elevated at both messenger RNA and
      protein levels, and the Rabl3 protein was significantly upregulated by upto 3.3
      fold in hepatocellular carcinoma compared with the paired normal hepatic tissues.
      Immunohistochemical analysis revealed that overexpressions of Rabl3 were 80.2% in
      hepatocellular carcinoma. Rabl3 is expressed at significantly higher rates in
      hepatocellular carcinoma compared with adjacent normal hepatic tissue (p < 0.01).
      Statistical analysis suggested the upregulation of Rabl3 was significantly
      associated with lymph node metastasis, tumor thrombus of the portal vein, and
      advanced clinical stage (p < 0.05). Furthermore, we found that overexpression of
      Rabl3 in hepatocellular carcinoma cells could significantly enhance cell
      proliferation and growth ability. Conversely, silencing Rabl3 by small hairpin
      RNA interference caused an inhibition of cell proliferation and growth. Our
      studies suggest that the Rabl3 is a valuable marker of hepatocellular carcinoma
      progression and that the overexpression of Rabl3 plays an important role in the
      development and pathogenesis of hepatocellular carcinoma.

PMID- 28443499
TI  - High expression of partitioning defective 3-like protein is associated with
      malignancy in colorectal cancer.
AB  - Partitioning defective 3-like protein is a novel cell polarity protein. Recently,
      partitioning defective 3-like protein has been demonstrated with tumor-promoting
      function by disrupting tight junction, inhibiting tumor suppressor liver kinase
      B1, and maintaining mammary stem cells. For the first time, we studied
      partitioning defective 3-like protein expression in malignant colorectal cancer.
      We used immunohistochemistry scoring system to evaluate partitioning defective 3
      like protein expression in 196 colorectal cancer tissues and 33 adjacent normal
      tissues. We found that colorectal cancer tissues had much stronger partitioning
      defective 3-like protein immunoreactivity than normal tissues, and colorectal
      cancer patients with positive partitioning defective 3-like protein expression
      were characterized with higher cancer stages, metastasis, poor tumor
      differentiation, larger tumor size, as well as high levels of colorectal cancer
      markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning
      defective 3-like protein overexpression was independently predictive of lower
      survival rate in colorectal cancer patients, even after adjusting the influence
      of cofactors. Moreover, we also found that partitioning defective 3-like protein
      was associated with rapid growing colorectal cancer, while knockdown of
      partitioning defective 3-like protein expression largely inhibited cancer cell
      proliferation. Our study provided the first evidence that partitioning defective
      3-like protein was overexpressed in colorectal cancer and associated with disease
      malignancy. Also, partitioning defective 3-like protein may serve as a promising
      prognostic marker and a potential therapeutic target for colorectal cancer
      treatment. Further study is necessary to understand the regulatory mechanism of
      partitioning defective 3-like protein in colorectal cancer and the feasibility of
      its application in clinic.

PMID- 28443500
TI  - Occurrence of TEM, SHV and CTX-M beta Lactamases in Clinical Isolates of Proteus
      Species in a Tertiary Care Center.
AB  - BACKGROUND: Extended spectrum beta lactamases (ESBL) are responsible for
      increased resistance to third generation cephalosporins. Proteus species is an
      important cause of both community acquired and nosocomial infections. The Proteus
      species is usually susceptible to beta lactam drugs but there is progressive
      increase in beta lactam resistance and recently, ESBLs are also fast spreading to
      this species. OBJECTIVE: This study was conducted to study ESBL production and
      occurrence of TEM, SHV and CTX-M beta lactamases in clinical isolates of Proteus
      species in a tertiary care center. METHOD: This prospective hospital based study
      was carried out in Microbiology, Kasturba Medical College, Mangalore over 9
      months. All non-duplicate consecutive Proteus isolates were identified and
      antibiotic susceptibility testing was done. ESBL detection was done by double
      disk synergy method and TEM, SHV, CTX-M genes were detected by PCR. RESULTS: 84
      Proteus isolates from urine (29), blood (1), respiratory secretions (2), tissue
      (20) and exudates (47) were included in the study. 20.2% (17) were ESBL positive
      by disk synergy method. CTX-M was present in 6, TEM in 2 and both in 9 isolates.
      SHV was not present in any isolate. CONCLUSION: Our findings showed that 20% of
      clinical isolates of Proteus species were ESBL producers. 52% of ESBL positive
      isolates carried both TEM and CTX-M genes followed by CTX-M alone (35%) and only
      11% had TEM alone. This stresses on the fact that ESBL detection should be done
      routinely in Proteus isolates and the genotype surveyed periodically for better
      management.

PMID- 28443501
TI  - Testicular Dysfunction is a Common Feature in Men with Type 2 Diabetes Mellitus
      in a Nigerian Tertiary Hospital.
AB  - BACKGROUND: Hypogonadism in male patients with diabetes mellitus is associated
      with older age, obesity and poor glycaemic control. The patterns of sperm count,
      testicular volume, sperm motility and morphology have also been reported to be
      abnormal in these patients, though reports are conflicting. The objectives of
      this study were to assess gonadal function and sperm parameters in Nigerian males
      with diabetes mellitus. METHODS: A study sample of 150 males consisting of 108
      patients and 56 age-matched controls were recruited. The ADAM questionnaire was
      used to obtain a clinical score for hypogonadism. Laboratory parameters measured
      were fasting plasma glucose, serum LH, FSH, free testosterone, total cholesterol,
      LDL, HDL and triglyceride. Testicular volume was measured with a Prader
      orchidometer. Total sperm count, sperm morphology and motility were assessed.
      RESULTS: Hypogonadism was present in 38.9% of males with diabetes compared to
      3.6% in controls. The patients with diabetes had significantly lower sperm count,
      reduced sperm motility with increased abnormal forms than the controls (p<0.001,
      p<0.001). Only 8.5% of the patients did not demonstrate any abnormality in
      testicular function. CONCLUSION: Poor sperm function was more common than
      hypogonadism and was associated with poor glycaemic control (p<0.001). Likewise,
      hypogonadism was significantly associated with poor glycaemic control (p<0.001).

PMID- 28443502
TI  - Fe3O4@SiO2@KIT-6 as an Efficient and Reusable Catalyst for the Synthesis of Novel
      Derivatives of 3,3'-((Aryl-1-phenyl-1H-pyrazol-4- yl)methylene)bis (1H-indole).
AB  - AIM AND OBJECTIVE: Korea advanced institute of science and technology cubic
      ordered mesoporous silica (KIT-6 mesoporous) silica coated magnetite
      nanoparticles, is an effective, ecobenign and recyclable catalyst for the
      electrophilic substitution reactions of indoles with various synthetized
      aldehydes to afford the corresponding novel diindolylmethanes in high yields and
      short reaction times. The catalyst can be recovered and reused without loss of
      activity. The work-up of the reaction consists of a simple separation, followed
      by concentration of the crude product and purification. The present methodology
      offers several advantages such as aqueous media, excellent yields, simple
      procedure, mild conditions and reduced environmental consequences. All of
      synthesized compounds are new and were characterized by IR, NMR and elemental
      analyses. MATERIALS AND METHODS: A mixture of synthetized pyrazolecarbaldehydes
      [24] (2.0mmol), indole (4.0mmol) and Fe3O4@SiO2@KIT-6 (0.04mmol) and H2O (10mL)
      were stirred at room temperature for the required reaction time according to
      Table 2. After completion of the reaction, the product was solved in CHCl3 (3*10
      mL) and insoluble catalyst was removed by filtration in the presence of an
      efficient magnetic bar. The organic phase including the product and CHCl3 was
      evaporated under vacuum. The resulting crude material was purified by
      recrystallization from EtOH to afford pure products. RESULTS: As part of our on
      interest for the development of efficient and environmentally friendly procedures
      for the synthesis of heterocyclic and pharmaceutical compounds, an efficient,
      facile and aqueous media was introduced for the synthesis of novel derivatives of
      diindolylmethanes containing pyrazole moiety. A variety of synthetized aldehyde
      compounds reacted smoothly with indoles to produce diindolylmethanes under these
      reaction conditions. The electron deficiency and the nature of the substituents
      on the aromatic ring show some effects on this conversion. All the reactions were
      run with catalytic amounts of catalysts. The best results gained with 0.04mmol of
      Fe3O4@SiO2@KIT-6 as a strong Lewis acid at room temperature in aqueous media.
      CONCLUSION: In conclusion, we have investigated the synthesized KIT-6 mesoporous
      silica coated magnetite nanoparticles (MMNPs) as a mild and efficient catalyst
      for the synthesis of novel diindolylmethanes coupled with pyrazole moiety in aqua
      media. The simplicity, easy workup together with the use of inexpensive,
      environmentally friendly and reusable catalyst, is the notable features of this
      catalytic procedure. To the best of our knowledge, this is the first report for
      the synthesis of a new library of diindolylmethane compound bearing pyrazole
      moiety that enhance the biological and pharmacological activity.

PMID- 28443503
TI  - Kratom and Future Treatment for the Opioids Addiction and Chronic Pain: Periculo
      Beneficium?
AB  - Kratom (Mitragynaspeciosa), a natural existing plant found in South-East Asia, is
      tradi-tionally used as an herb to help to elevate a person's energy and also to
      treat numerous medical ailments. Other than the analgesic property, kratom has
      been used as an agent to overcome opioid withdrawal as it contains natural
      alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist
      affinity on the opioid receptors, including mu (MU) and kappa (kappa). The role
      of neural reward pathway linked to MU-opioid receptors and both dopaminergic and
      GABA-ergic interneurons that express MU-opioid receptors were deliberated.
      However, kratom has been reported to be abused together with other illicit
      substances with high risk of potential addiction. There are also anecdotes of an
      adverse effect and toxicity of kratom, i.e. tremor, fatigue, seizure, and death.
      Different countries have distinctive regulation and policy on the plantation and
      use of this plant when most of the countries banned the use of it because of its
      addiction problems and side effects. The aim of this review is to highlight on
      the potential use of kratom, a unique 'herbs" as a substitution therapy for
      chronic pain and opioid addiction, based on the neurobiological perspective of
      pain and the underlying mechanism of actions of drug addiction.

PMID- 28443504
TI  - Potential Use of Modulators of Oxidative Stress as Add-on Therapy in Patients
      with Anxiety Disorders.
AB  - BACKGROUND: It is known that an increased oxidative stress is present in a wide
      range of diseases and, given the vulnerability of the central nervous system, its
      involvement has been in particular investigated in neurological and psychiatric
      diseases, including anxiety disorders. OBJECTIVE: In this review, we analyse the
      studies that have been conducted on the effects of oxidative stress modulators in
      anxiety, focusing on their possible clinical use. DISCUSSION AND CONCLUSION:
      While preclinical studies have shown a clear anxiolytic-like effect of different
      oxidative stress modulators, less significant results have been obtained from
      clinical studies. After having reviewed the possible reasons for the discrepancy
      between preclinical and clinical data, we encourage further studies aimed at
      better investigating the utility of the modulation of oxidative stress in humans,
      as an adjunctive therapy of the traditional integrated psychotherapeutic and
      pharmacological approach.

PMID- 28443505
TI  - Targeted Therapy of Ovarian Cancer with Angiogenesis Inhibitors.
AB  - Specific blocking of interactions between ligands and receptors along the
      angiogenic pathways represents an effective approach for enhancing the efficacy
      as well as reducing adverse effects of chemotherapy. Over the past decade, there
      was a rapid progression in the application of this therapeutic strategy in cancer
      treatment. Anti-angiogenic therapy is the most promising targeted therapy for
      ovarian cancer. The addition of bevacizumab to conventional chemotherapy, either
      in the first-line setting or at disease relapse, may improve overall survival
      (OS) of ovarian cancer patients, at least in a subset of patients with poor
      prognosis. In this article, we summarize published data on the major agents used
      for anti-angiogenic therapy in ovarian cancers. We will review the molecular
      mechanisms, results of clinical trial of existing agents and describe the
      development of new agents. The limitations and side effects of angiogenesis
      inhibitor are also discussed.

PMID- 28443507
TI  - Synthesis and Biological Activity of Unnatural Enediynes.
AB  - BACKGROUND: The first reports of the natural enediyne anticancer antibiotics date
      back to the late 1980s; since then, a great deal of interest has been devoted to
      the chemistry, biology and potential medical applications of this family of
      compounds. The biological activity of enediynes is linked to the presence of a
      highly unsaturated hex-1-ene-1,5-diyne system. The thermally induced
      transformation of this unit into a benzene sigma-sigma diradical (the Bergman
      cycloaromatization) is the key step of the antitumor properties of such
      compounds: 1,4-diaryl radicals are able to abstract H-atoms from the deoxyribose
      backbone of DNA, thus leading to DNA strand cleavage and ultimately cell death.
      METHODS: We undertook a structured search of bibliographic databases for peer
      reviewed research literature using focused and high quality papers. Research
      efforts addressed at understanding and mimicking the various processes involved
      in the targeting, activation and DNA cleavage associated with these products are
      described. The potential of a great number of non natural enediynes in the
      treatment of many infectious diseases, apart their role in anticancer drugs, such
      as antibacterial activity, protein degradation activity, has been reported
      Results: Due to the interesting mode of action of this class of compounds, the
      unique molecular architecture of enediynes has been exploited towards the
      synthesis of many non natural compounds in order to study and enhance their
      biological properties. Seventy-six papers were included in this review. It is
      divided in paragraphs that include: Carbo- oxygen-nitrogen- and sulfur-
      enediynes, polymers and macrocycles. The synthetic approaches to the different
      classes of compounds are discussed in detail together with the biological
      implications of the synthesized compounds Conclusion: The review summarizes the
      most recent advances in the synthesis and reactivity of non natural enediynes by
      focusing the attention particularly to the biological properties of the most
      interesting members of the family of carbo- and hetero- enediynes. The findings
      of this review confirm the importance of non natural enediynes as potential drugs
      in the treatment of cancer and many infectious diseases.

PMID- 28443506
TI  - Catestatin: A Master Regulator of Cardiovascular Functions.
AB  - BACKGROUND: Cardiovascular disease (CVD), the most common cause of death
      globally, accounts for ~30% of all deaths worldwide. Hypertension is a common
      contributor to morbidity and mortality from CVD. METHODS AND RESULTS: The plasma
      concentration of chromogranin A (CgA) is elevated in patients with CVD as well as
      patients with established human essential hypertension and heart failure (HF). In
      contrast, the plasma level of the CgA-derived peptide catestatin (CST) is
      diminished in human essential hypertension. Low conversion of CgA-to-CST has been
      associated with increased mortality in patients hospitalized with acute HF.
      Consistent with human findings, the lack of CST in CgA knockout (Chga-KO) mice
      eventuates in the development of hypertension and supplementation of CST to Chga
      KO mice restores blood pressure, implicating CST as a key player in regulating
      hypertension. In the peripheral system, CST decreases blood pressure by
      stimulating histamine release, inhibiting catecholamine secretion, or causing
      vasodilation. Centrally, CST improves baroreflex sensitivity (BRS) and heart rate
      variability (HRV) by exciting GABAergic neurons in the caudal ventrolateral
      medulla (CVLM) and pyramidal neurons of the central amygdala; CST also decreases
      BRS by exciting glutamatergic rostral ventrolateral medulla (RVLM) neurons. In
      addition, CST provides cardioprotection by inhibiting inotropy and lusitropy;
      activating mitochondrial KATP channels, and stimulating reperfusion injury
      salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways
      and consequent inhibition of mitochondrial permeability transition pore (mPTP).
      CST modulates cardiomyocyte Ca2+ levels by direct inhibition of Ca2+/calmodulin
      dependent protein kinase IIdelta (CaMKIIdelta) activity and consequent reduction
      in phosphorylation of phospholamban and ryanodine receptor 2, thereby providing
      support for a direct functional role of CST in the failing myocardium.
      CONCLUSION: These multitude of effects establish CST as a master regulator of
      cardiovascular functions.

PMID- 28443508
TI  - Nutritional Deficiency in Early Life Facilitates Aging-Associated Cognitive
      Decline.
AB  - BACKGROUND: Nutrition is important for the fetal developmental programming.
      Nutritional deficiency in early life could increase the susceptibility to many
      aging-related disorders including cognitive decline. OBJECTIVE: Our study aims to
      investigate the effect of early famine exposure on aging-associated cognitive
      function. METHODS: We recruited 6790 subjects born between 1956 to 1964 during
      which the Great Chinese Famine occurred (1959-1961). Cognitive function of these
      subjects were evaluated using the Mini-Mental State Examination (MMSE), the
      Activities of Daily Living scale (ADL), the Instrumental Activities of Daily
      Living scale (IADL) and the Clinical Dementia Rating (CDR). RESULTS: Our study
      identified that early exposure to the famine significantly increased the risk of
      cognitive impairments in later life, leading to higher prevalence of Mild
      Cognitive Impairment (MCI) and dementia. We also found the sex and rural-urban
      differences in this malnutrition-induced effect. Illiteracy, history of stroke or
      diabetes mellitus are great risk factors to facilitate the cognitive decline.
      CONCLUSION: These findings demonstrate that exposure to famine during early life
      including prenatal period and early childhood facilitates aging-associated
      cognitive deficits.

PMID- 28443509
TI  - Pharmacokinetics, Tissue Distribution and Excretion Study of Fluoresceinlabeled
      PS916 in Rats.
AB  - BACKGROUND: PS916, chitosan derivative with shown activities in atherosclerotic
      and fatty liver, is being investigated as an anti-atherosclerotic agent in
      clinical trials in China. METHODS: Fluorescein-labeled PS916 (PS916-FTC) was
      prepared by the reaction with fluorescein isothiocyanate. The pharmacokinetics
      and bio-disposition of PS916-FTC were studied in rats after oral or intravenous
      administration. RESULTS: Analysis of the plasma, urine, fecal and tissue samples
      collected at intervals up to 72 h revealed that PS916-FTC exhibited moderate
      volume of distribution (Vss, 0.650~0.748 L/kg), and low clearance (60.9~107
      mL/h/kg) after intravenous administration. The pharmacokinetics of PS916-FTC was
      characterized by low bioavailability (8.40%) after oral administration. The
      average accumulation ratio for PS916-FTC exposure after steady-state
      administration was 1.04. A two-compartmental pharmacokinetics model was employed.
      The urinary route was the major pathway (54.4%), and the fecal route was a minor
      pathway (6.29%) for PS916-FTC elimination after intravenous administration; the
      fecal route was the major pathway (79.0%) for PS916-FTC elimination after oral
      administration. CONCLUSION: PS916-FTC was widely distributed to most tissues in
      rats; relatively high levels of PS916-FTC in kidney and liver were observed after
      intravenous or oral administration. These findings supported the understanding of
      pharmacokinetics and bio-disposition of PS916 in rats and provide relevant
      information for future design of clinical studies. HIGHLIGHTS: 1) Fluorescein
      labeled PS916 was successfully synthesized. 2) A rapid and sensitive analytical
      method of PS916-FTC was validated. 3) The pharmacokinetic of PS916-FTC in rats
      was investigated. 4) The bio-distribution of PS916-FTC in rats was investigated.

PMID- 28443510
TI  - A Combination of Egg Yolk IgY and Phosvitin Inhibits the Growth of
      Enterotoxigenic Escherichia coli K88 and K99.
AB  - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is the main cause of fatal
      diarrhea in piglets during the first week of life and over the time of weaning.
      Pathogenesis of ETEC-causing diarrhea involves intestinal colonization mediated
      by fimbriae. Although, both IgY and egg yolk phosvitin (PV) possess antimicrobial
      activity, their combined activity has not been explored. A combination of IgY
      specific for ETEC and metal-chelating PV may show synergistic effect in reducing
      the growth of ETEC by inhibiting bacterial proliferation and stipulating
      protection against ETEC infection. OBJECTIVE: The goal of this study was to
      determine the effects of anti-ETEC IgY and PV on in vitro growth inhibition of
      ETEC strains possessing K88 and K99 fimbriae prevalent in the porcine population.
      METHODS: Anti-K88 and -K99 IgY antibodies were obtained from egg yolks of 23-week
      old Single- Comb White Leghorn hens immunized with K88 and K99 fimbriae of ETEC,
      respectively, with high titres sustained over 6 to 8 weeks of the immunization
      period. Specific IgY, PV, and PV-hydrolysate from alcalase-hydrolysis under high
      hydrostatic pressure (PVH-Alc-HHP) alone or in combination, were used to treat
      ETEC K88 and K99 cultures at optimal concentrations of 100 MUg/mL, 1 mg/mL, and 1
      mg/mL, respectively, for 24 h. RESULTS: PVH-Alc-HHP demonstrated the highest
      degree of hydrolysis, 38.9%. Combined use of IgY and PVH-Alc-HHP showed the
      highest bactericidal effect resulting in ETEC K88 and K99 growth inhibition of
      2.8 and 2.67 log CFU/mL, respectively. CONCLUSION: Combined IgY-PVH effectively
      control ETEC, therefore holds a great potential for microbial control in
      veterinary pharmaceutical industry.

PMID- 28443511
TI  - Current Approaches and Future Prospects of Nanomedicine in Tuberculosis Therapy.
AB  - BACKGROUND: Tuberculosis (TB), which is caused by the Mycobacterium tuberculosis,
      is a serious threat and one of the major health problems worldwide. OBJECTIVE: In
      recent years, an estimated of 9.6 million TB cases occurred and 1.5 million death
      occurred due to TB worldwide. CONCLUSION: The present review is an attempt to
      introduce this disease focusing on the pathophysiology of the disease, the
      current approaches and the related patents for treatment and the future planning
      for combating this disease.

PMID- 28443512
TI  - Clinical and Radiographic Features of Knee Osteoarthritis of Elderly Patients.
AB  - BACKGROUND: Knee osteoarthritis is a common pathology, characterized by a
      prevalence that increases with age. Absence of anatomo-clinical correlation is a
      complex management, particularly in a geriatric setting where it is not well
      studied. OBJECTIVE: The aim of the present study is to investigate the epidemio
      clinical profile, functional impairment and radiographic features of knee
      osteoarthritis in the old patients versus younger patients (<65 years). METHODS:
      Cross-sectional study includes patients who were monitored for 6 months at a
      rheumatology department for knee osteoarthritis. Epidemio-clinical,
      anthropometric and radiographic data were gathered. A comparison was made of
      these various characteristics between patients of over 65 years of age (group1;
      n=56) and those under 65 (group2; n=56). RESULTS: The mean age of the group 1
      patients was 71+/-5 with a clear feminine predominance. Comorbidity was observed
      in two thirds of cases. More than half of them were overweight. Gonalgia had been
      evolving for approximately 8.4+/-9.2 years and was bilateral in 82.6% of the
      cases and of mechanical type in 94.6% of the cases. The patients experienced an
      average pain scale of 65.2mm. Pain had an anterior site in major of cases. An
      axial deviation of the lower limbs were observed in 60.7% of the cases and a
      limited mobility of the knees in 48.2% of the cases. The mean value of Lequesne
      index was 11.02+/-4.8. The walking distance was not limited in 37.5% of the
      cases. Radiographically, knee osteoarthritis was bilateral in all cases and stage
      4 was observed in 50% of the cases. Comparative study showed that elderly
      patients had a smaller waist size (p=0.003), a longer course of gonalgia
      (p<0.0001), a widespread site of pain (p=0.004), and a more frequent limitation
      of walking distance (p<0.0001) as well as more axial deviation (p<0.0001) and
      joint mobility limitation (p=0.005). Gonalgia manifesting during rest was more
      frequent in elderly patients (p=0.001). In addition, impaired functioning
      (p=0.001) and the stage of radiographic damage (p=0.02) were more advanced in
      elderly patients. CONCLUSION: The present study shows that knee osteoarthritis is
      more severe in the elderly patients in terms of clinical presentation and
      functional impairment.

PMID- 28443513
TI  - Gastrointestinal Dysmotility and Infections in Systemic Sclerosis- An Indian
      Scenario.
AB  - INTRODUCTION: Systemic Sclerosis is known to involve the gastrointestinal system
      and can lead to multitude of problems predominantly affecting the GI motility.
      METHODS: It was a prospective, observational, single centre study of fifty
      consecutive patients with SSc who presented to rheumatology clinic. Gut score was
      assessed using UCLA SCTC GIT 2.0 questionnaire. 35 patients underwent esophago-
      gastro duodenoscopy(UGIE), 31 underwent esophageal manometry, 37 underwent
      lactulose breath test to assess orocaecal transit time (OCTT) and glucose breath
      test for detecting small intestinal bacterial overgrowth (SIBO) and 36 underwent
      gastric emptying scintigraphy to measure gastric emptying time. RESULTS: GI
      involvement was seen in 98% of patients, with most common symptom being
      regurgitation (78%). Mean T score of the GUT score was 0.60+/-0.27. In UGIE,
      esophagitis was seen in 30, of which 3 had candidiasis and 1 had HSV esophagitis.
      Hiatus hernia was noted in 10 patients. Mean lower esophageal sphincter pressure
      was 16.1+/- 12.7 mmHg with hypotensive sphincture in twelve patients. Esophageal
      peristaltic abnormalities were observed in 28(90%) patients. Gastric emptying was
      delayed in10/36 patients. OCTT was prolonged in 23/ 37 patients whereas SIBO was
      noted in 7/37. CONCLUSION: GI involvement is common in SSc with esophagus being
      most commonly affected. Motility abnormalities make them prone for super added
      infections especially infectious esophagitis and SIBO and should be investigated
      for early detection and treatment.

PMID- 28443514
TI  - Compound Libraries: Recent Advances and Their Applications in Drug Discovery.
AB  - BACKGROUND: Hit identification is the starting point of small-molecule drug
      discovery and is therefore very important to the pharmaceutical industry. One of
      the most important approaches to identify a new hit is to screen a compound
      library using an in vitro assay. High-throughput screening has made great
      contributions to drug discovery since the 1990s but requires expensive equipment
      and facilities, and its success depends on the size of the compound library.
      Recent progress in the development of compound libraries has provided more
      efficient ways to identify new hits for novel drug targets, thereby helping to
      promote the development of the pharmaceutical industry, especially for firstin-
      class drugs. METHODS: A multistage and systematic research of articles published
      between 1986 and 2017 has been performed, which was organized into 5 sections and
      discussed in detail. RESULTS: In this review, the sources and classification of
      compound libraries are summarized. The progress made in combinatorial libraries
      and DNA-encoded libraries is reviewed. Library design methods, especially for
      focused libraries, are introduced in detail. In the final part, the status of the
      compound libraries at WuXi is reported. CONCLUSION: The progress related to
      compound libraries, especially drug template libraries, DELs, and focused
      libraries, will help to identify better hits for novel drug targets and promote
      the development of the pharmaceutical industry. Moreover, these libraries can
      facilitate hit identification, which benefits most research organizations,
      including academics and small companies.

PMID- 28443515
TI  - Indication of Bevacizumab for Cerebral Radiation Necrosis.
AB  - BACKGROUND: The effect of bevacizumab (BVZ) for Cerebral Radiation Necrosis (CRN)
      was clear. However, the indications of BVZ had no reports. OBJECTIVE: The aim of
      the paper was to investigate the indications of BVZ for CRN. METHODS: Fourteen
      CRN patients (confirmed by imaging diagnosis) who underwent BVZ treatment between
      June 2011 and December 2014 were analyzed. BVZ was administered (5mg/kg body
      weight) once every three to four weeks for at least three cycles. Contrast
      enhanced T1 MRI signal intensity changes were measured after BVZ treatment, to
      evaluate the clinical efficacy of BVZ and the recurrence and progression of CRN.
      Three patients who were followed for a longer duration were described in detail.
      The main observations included the indications and (the) use of BVZ for CRN.
      RESULTS: Most patients undergoing BVZ treatment for CRN exhibited recurrence. One
      of the three patients described in detail was asymptomatic; CRN was reduced but
      then progressed, and a second course of BVZ failed. The other two patients showed
      obvious symptoms of primary CRN; CRN was significantly reduced, but then
      progressed with mild symptoms. A second short course of BVZ showed poor efficacy
      in one patient who demonstrated long-term stability after BVZ withdrawal. Second
      long course of BVZ resulted in further aggravation of CRN in the other patient,
      and a re-examination revealed spontaneous remission of CRN. CONCLUSION: Symptoms
      are an indication of BVZ treatment for primary CRN.

PMID- 28443516
TI  - Synergistic Effect of Graphene Oxide Coated Nanotised Apigenin with Paclitaxel
      (GO-NA/PTX): A ROS Dependent Mitochondrial Mediated Apoptosis in Ovarian Cancer.
AB  - BACKGROUND: Ovarian cancer is most lethal among all gynecologic malignancies.
      Paclitaxel (PTX) is well used chemotherapeutic regimen for cancer control;
      however its undesired toxicity has been a matter of concern for clinicians. Here,
      we used the graphene oxide coated nanotised apigenin (GO-NA) to enhance the
      efficacy of paclitaxel. OBJECTIVE: The combined use of paclitaxel (PTX) and
      nanotised apigenin (NA) may reduce the PTX dose and increase the efficacy.
      METHODS: GO and GO-Apigenin was prepared by modified Hummers method and the
      nanoparticles were characterized by dynamic light scattering and transmission
      electron microscopy. SKOV-3 cells were treated by DMSO, Group I (Control)-McCoy's
      5A Medium, Group II-Paclitaxel (5nM), Group III- Nanotised Apigenin (GO-NA-10uM),
      Group IV- Paclitaxel (5nM) + GO-NA (10uM). Cell viability and IC-50 value were
      determined by MTT assay, synergism by Compusyn software, ROS by DCFH-DA assay,
      SOD activity by kit and MMP were examined by JC-1 and mitotracker/DAPI staining,
      cell cycle by flow cytometry, mRNA and protein level by Real Time-PCR and Western
      blot respectively Results: Results showed that GO-NA-PTX enhanced the anti
      proliferative effect in synergistic manner as compare to GO-NA and PTX alone. GO
      NA-PTX significantly suppressed the SOD activity, promotes the ROS accumulation,
      mitochondrial depolarization, DNA integrity and cell cycle arrest collectively
      accord the apoptosis. Results of immunocytochemistry, RT-PCR and western blot
      showed up-regulation of caspase-3, Bax, and down-regulation of Bcl-2. CONCLUSION:
      The combination of PTX with GO-NA produces synergistic effects in SKOV-3 cells
      via the modulation of pro and anti-apoptotic gene and may reduce side effects of
      PTX.

PMID- 28443517
TI  - 1,3,4-Oxadiazoles as Telomerase Inhibitor: Potential Anticancer Agents.
AB  - Cancer is a rapidly growing disease of current era which poses a major life
      threaten situation to human beings. Continuous research is going on in the
      direction to develop effective molecules for the treatment of the cancer. These
      efforts include searching of more active heterocyclic compounds possessing
      potential anticancer activity. The 1,3,4-Oxadiazole scaffold is a five member
      heterocyclic ring having versatile activities and created interest for synthetic
      organic and medicinal chemists for the designing of novel compounds having
      anticancer activity. The important mechanism behind tumor suppression by 1,3,4
      Oxadiazole is related with the inhibition of different growth factors, enzymes
      and kinases etc. The current literature surveys revealed that 1,3,4-Oxadiazole is
      a promising lead for anti-cancer agents by the inhibition of telomerase activity.
      In cancerous cells telomerase enzyme is activated which maintains and restores
      the telomere which leads to cell proliferation. The telomerase inhibitors with
      enhanced specificity and improved pharmacokinetics have been considered for
      design and development of novel anti-cancer agents. This review focuses primarily
      on telomerase enzyme its function and mechanism of action. It also describes the
      interaction of telomerase enzyme with 1,3,4-Oxadiazole inhibitors including their
      structure activity relationships (SARs). With the knowledge of this molecular
      target, structural insights and SARs, this review may be helpful for (medicinal)
      chemists to design more potent, safe, selective and cost effective anti-cancer
      agents.

PMID- 28443518
TI  - Limitations of Current Therapeutic Options, Possible Drug Targets and Scope of
      Natural Products in Control of Leishmaniasis.
AB  - Soon after the identification of Leishmania parasite as a causative agent, the
      pentavalent antimony compounds have been the mainstay to treat all forms of
      leishmaniasis. Due to growing incidences of antimony resistant parasites and
      unavailability of true antileishmanial compounds, few drugs like pentamidine
      (antimicrobial), amphotericin B (antifungal) or miltefosine (antitumor) are
      currently being used but these are associated with serious side effects.
      Unfortunately, the emergence of amphotericin B and miltefosine resistant
      parasites in clinical settings has further questioned their sustained use in
      leishmanial control. Moreover, the parameters of protective immunity are not well
      understood in leishmanial pathogenesis therefore, a vaccine candidate, either
      prophylactic or preventive, is still an unrealized goal. In addition, the
      emergence of insecticide resistance sand flies in disease endemic regions also
      stance a big threat for the current elimination strategies. Therefore, in lieu of
      the limited drug regimen and unavailability of a vaccine, the necessity of a true
      antileishmanial agent is always there. Although, leishmanial infections have been
      neglected for many decades but recent studies have identified potential drug
      targets that could be targeted to control the growth of parasites. In recent past
      many compounds derived from natural sources have also been shown to possess
      excellent antiparasitic potential; however, most of these studies are limited to
      primary evaluation and only a few have reached to clinical levels. In this
      review, we discuss the limitations of current drug regimen, explore possible drug
      targets of Leishmania species and summarize wide range of compounds isolated from
      various natural sources that are worth screening as antileishmanial drug
      candidates.

PMID- 28443519
TI  - Atranorin - An Interesting Lichen Secondary Metabolite.
AB  - BACKGROUND: Atranorin, a compound with the depside structure, is one of the most
      common lichen secondary metabolites, characteristic for numerous lichen families
      but rarely found in some mosses and higher plants. Over the years various
      biological properties of atranorin were examined. OBJECTIVE: This review
      summarizes the studies on atranorin, focusing on a number of biological
      activities in different fields. The literature describes anti-inflammatory,
      analgesic, as well as wound healing, antibacterial, antifungal, cytotoxic,
      antioxidant, antiviral, and immunomodulatory activities of the depside.
      Furthermore, lack of toxicity of atranorin was confirmed in the animals' in vivo
      assays. CONCLUSION: In conclusion, atranorin seems to be an interesting lichen
      substance, which needs to be investigated in more detail in order to allow
      further applications, e.g. in pharmacy, medicine or cosmetology.

PMID- 28443521
TI  - Synthesis, Anticancer Screening and Molecular Docking Studies of New Heterocycles
      with Trimethoxyphenyl Scaffold as Combretastatin Analogues.
AB  - BACKGROUND: In this study, synthesis, molecular docking and anticancer screening
      of new series of substituted heterocycles with trimethoxy phenyl scaffold as
      Combretastatin analogues were described. Substituted pyridines were synthesized
      via the reaction of (E)-3-(dimethylamino)-1-(3,4,5- trimethoxyphenyl)prop-2-en-1
      one (2) with active methylene reagents. Substituted pyrimidines were prepared by
      the reaction of the enaminone (2) with heterocyclic amines and 6-amino
      thiouracil. Furthermore, a series of pyrazoles substituted with trimethoxyphenyl
      scaffold were prepared by the reaction of the enaminone 2, with selected examples
      of hydrazonoyl halides. CONCLUSION: The cytotoxic effect of the newly compounds
      was evaluated against HePG-2, HCT-116, MCF-7 and PC3 cancer cell lines. Among the
      new products, compounds 2, 3, 7 and 10 were found to exhibit promising results as
      anticancer agents. The IC50 values of 2, 3 and 7 were 54.6, 77.4 and 47.4 on PC3
      respectively. Also, compound 2 had IC50 28.06 on MCF7. Moreover, the selectivity
      index indicated that compounds 2 and 3 are safe.

PMID- 28443520
TI  - Recent Advances on 3-Hydroxyflavone Derivatives: Structures and Properties.
AB  - Flavonoids are naturally occurring phenolic compounds named as 2-phenyl-1
      benzopyran- 4-one and classified into several subclasses according to their basic
      chemical structures such as flavones, flavonols, flavanones, flavanonols, and
      flavanols. Among them, flavonols (3-hydroxyflavone), containing a 3-hydroxyl
      group in association with its 4-keto group and double bond between 2- and 3-
      carbon atoms, have the best electron conjugated skeleton in flavonoid family,
      providing several resonance structures and chelating ability, through which
      various pharmacological activities such as antiviral, antitumour, anti
      inflammatory, anticholinesterase, cytotoxicity and particularly high antioxidant
      activity are demonstrated. They prevent generation of free radicals and are used
      as food preservatives. Their strong electron conjugation provides them with
      fluorescent property, which make them used as imaging agents for therapeutic
      purpose.

PMID- 28443522
TI  - Legal and organisational innovation in the Italian pharmacy system: commercial vs
      public interest.
AB  - Pharmacy services are undoubtedly an important part of primary care. Pharmacists
      are entrepreneurs and simultaneously they are entrusted with a public mission in
      the health care sector. Pharmacies then reflect a contrast between a
      commercial/economic objective and public interest, which is to be identified with
      citizens' universal right to health care services. This is the reason why in
      Italy, as in many other EU countries, pharmacies supply their services according
      to a prior authorisation granted by public authorities. In common with many EU
      countries, this authorisation is secured according to a demographic criterion. It
      is only by means of these licensed pharmacies that citizens can buy drugs under
      medical prescription. Accordingly, the health system is to be driven by public
      interest, which has yet to prove how competing interests may be regulated in
      serving health needs. In the light of EU law, the article advocates for an
      innovative legal and organisational tool whereby to organise the Italian pharmacy
      system in order to combine economic consideration and public benefit.

PMID- 28443523
TI  - Do Non-Reflective Thinkers Apply Extreme Personal Meanings to their Activated
      Moods?
AB  - BACKGROUND: The integrative cognitive model of mood swings proposes that mood
      symptoms are driven by extreme, self-referent appraisals. For example, if
      activated mood is appraised positively, this prompts selection of mood regulation
      strategies that act to up-regulate mood. Appraisals are driven by fast and
      automatic Type 1 cognitive processes, which, left unchecked, can cause activated
      mood to escalate. AIMS: It was hypothesized that greater propensity to override
      these automatic processes by engaging in reflective (Type 2) thinking would be
      negatively associated with extreme appraisals of activation and activation.
      METHOD: Study 1 (n = 150) was a cross-sectional survey consisting of measures of
      activation, extreme appraisals, and an objective performance-based measure of the
      propensity to engage in reflective thought (cognitive reflection test; CRT). In
      Study 2 (n = 241) participants completed these measures plus three alternative
      measures of effortful cognitive engagement (CRT-2, Need for Cognition and
      Actively Open-Minded Thinking). RESULTS: In Study 1, propensity to engage in
      reflective thought (higher CRT scores) was not significantly associated with
      activated mood or extreme appraisals, but activated mood and extreme appraisals
      were positively correlated. In study 2, the association between activation and
      extreme appraisals was replicated. Predicted associations between alternative
      measures of reflective thinking, activated mood, and extreme appraisals were not
      found. CONCLUSIONS: Extreme appraisals of internal states may be a psychological
      mechanism underlying activated mood. Propensity to reflect on and override
      default cognitions was unrelated to these extreme appraisals and activated mood.
      Further research in a clinical sample using mood-relevant measures of reflective
      thinking is warranted.

PMID- 28443524
TI  - Risk factors for prelacteal feeding in sub-Saharan Africa: a multilevel analysis
      of population data from twenty-two countries.
AB  - OBJECTIVE: To examine the risk factors of prelacteal feeding (PLF) among mothers
      in sub-Saharan Africa (SSA). DESIGN: We pooled data from Demographic and Health
      Surveys in twenty-two SSA countries. The key outcome variable was PLF. A
      multilevel logistic regression model was used to explore factors associated with
      PLF. SETTING: Demographic and Health Surveys in twenty-two SSA countries.
      SUBJECTS: Mother-baby pairs (n 95348). RESULTS: Prevalence of PLF in SSA was 32.2
      %. Plain water (22.1 %), milk other than breast milk (5.0 %) and sugar or glucose
      water (4.1 %) were the predominant prelacteal feeds. In the multivariable
      analysis, mothers who had caesarean section delivery had 2.25 times the odds of
      giving prelacteal feeds compared with mothers who had spontaneous vaginal
      delivery (adjusted OR=2.25; 95 % CI 2.06, 2.46). Other factors that were
      significantly associated with increased likelihood of PLF were mother's lower
      educational status, first birth rank, fourth or above birth rank with preceding
      birth interval less than or equal to 24 months, lower number of antenatal care
      visits, home delivery, multiple birth, male infant, as well as having an average
      or small sized baby at birth. Mothers aged 20-34 years were less likely to give
      prelacteal feeds compared with mothers aged <=19 years. Belonging to the second,
      middle or fourth wealth quintile was associated with lower likelihood of PLF
      compared with the highest quintile. CONCLUSIONS: To achieve optimal breast
      feeding, there is a need to discourage breast-feeding practices such as PLF.
      Breast-feeding promotion programmes should target the at-risk sub-population
      groups discovered in our study.

PMID- 28443525
TI  - Frosting on the cake: pictures on food packaging bias serving size - CORRIGENDUM.

PMID- 28443526
TI  - Transformation of excess mortality in people with schizophrenia and bipolar
      disorder in Taiwan.
AB  - BACKGROUND: Given the concerns regarding the adverse health outcomes associated
      with weight gain and metabolic syndrome in relation to use of second-generation
      antipsychotics (SGAs), we aimed in this study to explore whether the increase in
      the use of SGAs would have any impacts on the trend of excess mortality in people
      with schizophrenia and bipolar disorder (BPD). METHOD: Two nationwide samples of
      individuals with schizophrenia and BPD were identified in Taiwan's National
      Health Insurance Research Database in 2003 and in 2008, respectively. Age- and
      gender-standardized mortality ratios (SMRs) were calculated for each of the 3
      year observation periods. The SMRs were compared between the calendar year
      cohorts, by disease group, and by causes of death. RESULTS: The mortality gap for
      people with schizophrenia decreased slightly, revealing an SMR of 3.40 (95% CI
      3.30-3.50) for the 2003 cohort and 3.14 (3.06-3.23) for the 2008 cohort. The
      mortality gap for BPD individuals remained relatively stable with only those aged
      15-44 years having an SMR rising significantly from 7.04 (6.38-7.76) to 9.10
      (8.44-9.79). Additionally, in this group of BPD patients aged 15-44 years, the
      natural-cause-SMR increased from 5.65 (4.93-6.44) to 7.16 (6.46-7.91).
      CONCLUSIONS: Compared with the general population, the gap in the excess
      mortality for people with schizophrenia reduced slightly. However, the over 200%
      difference between the cohorts in the excess mortality for BPD individuals aged
      15-44 years could be a warning sign. Future research to further examine the
      related factors underlying those changes is warranted.

PMID- 28443527
TI  - An investigation into the effects of maternal supplementation with excess iodine
      on the mechanisms and impacts of reduced IgG absorption in the lamb postpartum.
AB  - An experiment was conducted to determine: (1) the effect of excess maternal I
      supplementation on the thyroid hormone status of the ewe and her progeny; (2)
      potential mechanisms underpinning the failure of passive transfer associated with
      excess I and (3) the growing lambs' response to natural gastrointestinal
      infection. Twin-bearing ewes received one of two treatments (n 32/treatment
      group): basal diet (C) or C plus 26.6 mg of iodine/ewe per d (I), supplied as
      calcium iodate. Ewes were individually fed from day 119 of gestation to
      parturition. Progeny of I ewes had lower (P<0.01) serum IgG concentrations from
      24 h to 28 d postpartum but higher serum IgG concentrations at day 70 postpartum
      (P<0.05). I supplementation increased the relative expression of Fc receptor,
      IgA, IgM high affinity and polymeric Ig receptor in the ileum of the lamb at 24 h
      postpartum; however, thyroid hormone receptor-beta (THRB) and beta-2
      microglobulin (B2M) expression declined (P<0.05). Progeny of I ewes had higher
      growth rates to weaning (P<0.05) and lower faecal egg count (FEC) for Nematodirus
      battus (P<0.05) between weeks 6 and 10 postpartum. In conclusion, excess maternal
      I supplementation negatively affected the thyroid hormone status, serum IgG
      concentration, ileal morphology and the gene expression of THRB and B2M in the
      ileum and ras-related protein (RAB) RAB25 and the mucin gene (MUC) MUC1 in the
      duodenum of the lamb postpartum. These effects were followed by an enhancement of
      average daily gain and lower N. battus FEC in the pre-weaning period of I
      supplemented lambs.

PMID- 28443528
TI  - Understanding medusahead low intake and palatability through in vitro
      digestibility and fermentation kinetics.
AB  - The low intake of medusahead grass (Taeniatherum caput-medusae ssp. asperum) by
      sheep is attributed to the high silica content of the plant and its negative
      impact on digestibility, making this weed a successful competitor in grazed plant
      communities. The goals of this study were to determine the influence of (1) plant
      maturity stage (from late vegetative stage to beginning of senescence and
      thatch), (2) particle size (1, 5, 10 and 20 mm), and (3) high-quality feeds
      (alfalfa hay and a high-energy concentrate) on fermentation kinetics and apparent
      digestibility of medusahead relative to palatable feeds (alfalfa and tall fescue
      hays, and high-energy concentrates). In vitro gas production was estimated and
      apparent digestible organic matter (DOM) of the substrates was assessed after
      incubation. Medusahead from late vegetative to senescence stage had greater DOM
      (65% to 71%; P0.05), and lower than the high-energy concentrates assayed (77% to
      79%; P0.05) on digestibility parameters were observed by the addition of high
      quality feeds to medusahead. Slow fermentation kinetics and a significant
      inhibitory effect of particle size on apparent digestibility of organic matter
      contribute to explain the low use of medusahead by sheep. Such inhibitory effect
      may also underlie the lack of positive associative effects observed during the
      study.

PMID- 28443529
TI  - Selective attention and mismatch negativity in antipsychotic-naive, first-episode
      schizophrenia patients before and after 6 months of antipsychotic monotherapy.
AB  - BACKGROUND: Attention deficits have been frequently reported in schizophrenia. It
      has been suggested that treatment with second-generation antipsychotics can
      ameliorate these deficits. In this study, the influence of 6 months treatment
      with quetiapine, a compound with less affinity for dopamine D2 receptors than for
      serotonergic 5-HT2A receptors, on electrophysiological parameters of attention
      was investigated in a group of antipsychotic-naive, first-episode schizophrenia
      patients compared with a group of age- and gender-matched healthy controls.
      METHOD: A total of 34 first-episode, antipsychotic-naive patients with
      schizophrenia and an equal number of healthy controls were tested in a selective
      attention and a typical mismatch negativity (MMN) paradigm at baseline and after
      6 months. The patients were treated with quetiapine according to their clinical
      needs during the period between baseline and follow-up, whereas controls received
      no treatment. RESULTS: Patients showed lower MMN and P200 amplitude than healthy
      controls in the selective attention paradigm at baseline, while this was not the
      case for MMN of the typical MMN paradigm. Interestingly, after 6 months
      treatment, this MMN deficit was only ameliorated in patients treated with above
      median dosages of quetiapine. Patients had lower P3B amplitude, yet showed
      similar levels of processing negativity and N100 amplitude compared with healthy
      controls, both at baseline and follow-up. CONCLUSIONS: The results indicate that
      deficits in MMN, P200 and P3B amplitude are present at early stages of
      schizophrenia, although depending on the paradigm used. Furthermore, the results
      indicate that 6 months quetiapine treatment ameliorates MMN but not P3B deficits,
      and only in those subjects on higher dosages.

PMID- 28443530
TI  - Negative energy balance and loss of body mass and fat-free mass in military
      personnel subsisting on combat rations during training and combat operations: a
      comment on Tassone and Baker.

PMID- 28443531
TI  - Probiotics to prevent necrotising enterocolitis and nosocomial infection in very
      low birth weight preterm infants.
AB  - The aim of the study was to determine whether routine probiotic supplementation
      (RPS) with Lactobacillus rhamnosus GG (LGG) or Lactobacillus acidophilus
      +Lactobacillus bifidum is associated with reduced risk of necrotising
      enterocolitis (NEC)>=Stage II in preterm neonates born at <=32 weeks' gestation.
      We conducted a retrospective cohort study on the effect of probiotic
      supplementation in very low birth weight infants in our neonatal unit by
      comparing two periods: before and after supplementation. The incidence of
      NEC>=Stage II, late-onset sepsis and all-cause mortality was compared for an
      equal period 'before' (Period I) and 'after' (Period II) RPS with LGG or L.
      acidophillus+L. bifidum. Multivariate logistic regression analysis was conducted
      to adjust for relevant confounders. The study population was composed of 261
      neonates (Period I v. II: 134 v. 127) with comparable gestation duration and
      birth weights. In <32 weeks, we observed a significant reduction in NEC>=Stage II
      (11.3 v. 4.8 %), late-onset sepsis (16 v. 10.5 %) and mortality (19.4 v. 2.3 %).
      The benefits in neonates aged <=27 weeks did not reach statistical significance.
      RPS with LGG or L. acidophillus+L. bifidum is associated with a reduced risk of
      NEC>=Stage II, late-onset sepsis and mortality in preterm neonates born at <=32
      weeks' gestation.

PMID- 28443532
TI  - A writer's guide to education scholarship: Quantitative methodologies for medical
      education research (part 1).
AB  - BACKGROUND: Quantitative research is one of the many research methods used to
      help educators advance their understanding of questions in medical education.
      However, little research has been done on how to succeed in publishing in this
      area. OBJECTIVE: We conducted a scoping review to identify key recommendations
      and reporting guidelines for quantitative educational research and scholarship.
      METHODS: Medline, ERIC, and Google Scholar were searched for English-language
      articles published between 2006 and January 2016 using the search terms,
      "research design," "quantitative," "quantitative methods," and "medical
      education." A hand search was completed for additional references during the full
      text review. Titles/abstracts were reviewed by two authors (BT, PC) and included
      if they focused on quantitative research in medical education and outlined
      reporting guidelines, or provided recommendations on conducting quantitative
      research. One hundred articles were reviewed in parallel with the first 30 used
      for calibration and the subsequent 70 to calculate Cohen's kappa coefficient. Two
      reviewers (BT, PC) conducted a full text review and extracted recommendations and
      reporting guidelines. A simple thematic analysis summarized the extracted
      recommendations. RESULTS: Sixty-one articles were reviewed in full, and 157
      recommendations were extracted. The thematic analysis identified 86 items, 14
      categories, and 3 themes. Fourteen quality evaluation tools and reporting
      guidelines were found. Discussion This paper provides guidance for junior
      researchers in the form of key quality markers and reporting guidelines. We hope
      that quantitative researchers in medical education will be informed by the
      results and that further work will be done to refine the list of recommendations.

PMID- 28443534
TI  - Developing an international scoring system for a consensus-based social cognition
      measure: MSCEIT-managing emotions.
AB  - BACKGROUND: Measures of social cognition are increasingly being applied to
      psychopathology, including studies of schizophrenia and other psychotic
      disorders. Tests of social cognition present unique challenges for international
      adaptations. The Mayer-Salovey-Caruso Emotional Intelligence Test, Managing
      Emotions Branch (MSCEIT-ME) is a commonly-used social cognition test that
      involves the evaluation of social scenarios presented in vignettes. METHOD: This
      paper presents evaluations of translations of this test in six different
      languages based on representative samples from the relevant countries. The goal
      was to identify items from the MSCEIT-ME that show different response patterns
      across countries using indices of discrepancy and content validity criteria. An
      international version of the MSCEIT-ME scoring was developed that excludes items
      that showed undesirable properties across countries. RESULTS: We then confirmed
      that this new version had better performance (i.e. less discrepancy across
      regions) in international samples than the version based on the original norms.
      Additionally, it provides scores that are comparable to ratings based on local
      norms. CONCLUSIONS: This paper shows that it is possible to adapt complex social
      cognitive tasks so they can provide valid data across different cultural
      contexts.

PMID- 28443533
TI  - Childhood adversity, adult stress, and the risk of major depression or
      generalized anxiety disorder in US soldiers: a test of the stress sensitization
      hypothesis.
AB  - BACKGROUND: The stress sensitization theory hypothesizes that individuals exposed
      to childhood adversity will be more vulnerable to mental disorders from proximal
      stressors. We aimed to test this theory with respect to risk of 30-day major
      depressive episode (MDE) and generalized anxiety disorder (GAD) among new US Army
      soldiers. METHODS: The sample consisted of 30 436 new soldier recruits in the
      Army Study to Assess Risk and Resilience (Army STARRS). Generalized linear models
      were constructed, and additive interactions between childhood maltreatment
      profiles and level of 12-month stressful experiences on the risk of 30-day MDE
      and GAD were analyzed. RESULTS: Stress sensitization was observed in models of
      past 30-day MDE (chi2 8 = 17.6, p = 0.025) and GAD (chi2 8 = 26.8, p = 0.001).
      This sensitization only occurred at high (3+) levels of reported 12-month
      stressful experiences. In pairwise comparisons for the risk of 30-day MDE, the
      risk difference between 3+ stressful experiences and no stressful experiences was
      significantly greater for all maltreatment profiles relative to No Maltreatment.
      Similar results were found with the risk for 30-day GAD with the exception of the
      risk difference for Episodic Emotional and Sexual Abuse, which did not differ
      statistically from No Maltreatment. CONCLUSIONS: New soldiers are at an increased
      risk of 30-day MDE or GAD following recent stressful experiences if they were
      exposed to childhood maltreatment. Particularly in the military with an abundance
      of unique stressors, attempts to identify this population and improve stress
      management may be useful in the effort to reduce the risk of mental disorders.

PMID- 28443535
TI  - Effects of immunocastration and beta-adrenergic agonists on the performance and
      carcass traits of feedlot finished Nellore cattle.
AB  - beta-Adrenergic agonists (beta-AA) are non-hormonal growth promoters which
      promote muscle hypertrophy in supplemented animals. The effects of two beta-AA in
      combination with the immunocastration technique on the performance and carcass
      traits were evaluated using 96 feedlot Nellore males in a randomized complete
      block design with two sex conditions (immunocastrated (IC) v. non-castrated (NC))
      and three treatments: CON (no beta-agonists added), RH (300 mg of ractopamine
      hydrochloride/day, for 33 days) or ZH (80 mg of zilpaterol.hydrochloride
      animal/day for 30 days, removed 3 days for required withdrawal period). The trial
      was carried for 100 days where in the first 70 days animals did not receive beta
      AA (phase 1) and during the last 30 days they were treated with beta-AA (phase
      2). The performance and ultrasound measurements of longissimus muscle area (LMA),
      backfat thickness (BFT) and rump fat thickness (RFT) were evaluated in both
      phases. No sex condition v. treatment interactions were observed for any trait.
      The NC animals had higher average daily gain (ADG) and final BW than the IC
      animals, but they did not differ in dry matter intake (DMI) and feed efficiency
      (gain to feed). The NC animals showed greater LMA (P=0.0001) and hot carcass
      weight (P=0.0006), and smaller BFT (P=0.0007), RFT (P=0.0039) and percentage of
      kidney, pelvic and heart fat (P<0.0001) when compared with IC animals. The
      animals fed ZH showed greater ADG (P=0.0002), G : F (P<0.0001) and dressing per
      cent (P=0.0136) than those fed RH and CON diets. No differences in BW and DMI
      were observed. A interaction between treatment and time on feed was observed for
      LMA and BFT, in which the animals fed ZH diet showed greater LMA (P<0.01) and
      lower BFT (P<0.01) at 100 days than the animals fed RH and CON diets, whereas RH
      and CON diets did not differ. Immunocastration decreases muscle development and
      increases carcass finishing. In contrast, beta-AA increases muscle and decreases
      fat deposition. The ZH has a higher action on the muscle metabolism than animals
      fed RH diet. However, RH diet achieves a better balance because it has an
      intermediary performance between non-supplemented and ZH animals and does not
      decrease the carcass fat.

PMID- 28443537
TI  - The Legacy of Genetic Analysis Advances Contemporary Research with Escherichia
      coli K-12 and Salmonella enterica serovar Typhimurium LT2.
AB  - Escherichia coli K-12 and Salmonella enterica serovar Typhimurium LT2 became
      standard organisms for genetic analysis during the Truman administration. Half a
      century later, genetic analysis with these strains had become an art form,
      interpreted through 23 articles in the ambitious two-volume masterpiece edited by
      the late Fred Neidhardt and colleagues. These legacy articles now are available
      through EcoSal Plus, so as to inform and inspire contemporary genetic analyses in
      these standard organisms and their relatives.

PMID- 28443538
TI  - Iohexol Clearance for Determination of Glomerular Filtration Rate in Cynomolgus
      Monkeys (Macaca fascicularis).
AB  - The purpose of this study was to validate a method for determine the glomerular
      filtration rate (GFR) in healthy cynomolgus monkeys by using iohexol. Eighteen
      healthy cynomolgus macaque monkeys (age, 4 to 6 y [mean, 5 y]; weight, 2 to 6 kg
      [mean, 4 kg]) were randomly entered into 3 different doses groups (3 male and 3
      female macaques per group) of 30, 60, 90 mg I/kg to receive an intravenous bolus
      injection of iohexol. Serum iohexol concentrations were determined by using
      liquid chromatography-tandem mass spectrometry, and clearance rate were
      determined by using WinNonlin software. The GFR value (mean +/- SD) of each dose
      group was 2.50 +/- 0.321, 2.65 +/- 0.529, and 2.75 +/- 0.385 mL/min/kg. These
      values did not differ significantly between dose levels or sexes. Iohexol
      clearance is a simple, precise method that is suitable for the determination of
      GFR in cynomolgus monkeys.

PMID- 28443539
TI  - Achieving progress on ending the death penalty.

PMID- 28443540
TI  - Prospects for neonatal intensive care.

PMID- 28443541
TI  - Discuss prostate cancer screening with your doctor.

PMID- 28443542
TI  - The Global Financing Facility-towards a new way of financing for development.

PMID- 28443543
TI  - Offline: A voice from the American wilderness.

PMID- 28443544
TI  - A psychiatrist's search for resilience.

PMID- 28443545
TI  - Socialising the genome.

PMID- 28443546
TI  - Contraception, safe abortion, and the Zika response.

PMID- 28443547
TI  - Prehospital transfer strategies and tranexamic acid during major trauma.

PMID- 28443548
TI  - Obesity management in primary care.

PMID- 28443549
TI  - Obesity management in primary care.

PMID- 28443550
TI  - Obesity management in primary care.

PMID- 28443551
TI  - Obesity management in primary care - Authors' reply.

PMID- 28443552
TI  - Optical coherence tomography-guided PCI.

PMID- 28443553
TI  - Optical coherence tomography-guided PCI - Authors' reply.

PMID- 28443554
TI  - Stents versus bypass surgery for left main stem stenosis.

PMID- 28443555
TI  - Acute bacterial meningitis in adults.

PMID- 28443556
TI  - Stents versus bypass surgery for left main stem stenosis - Authors' reply.

PMID- 28443557
TI  - Acute bacterial meningitis in adults - Authors' reply.

PMID- 28443558
TI  - Towards evidence-based resuscitation of the newborn infant.
AB  - Effective resuscitation of the newborn infant has the potential to save many
      lives around the world and reduce disabilities in children who survive peripartum
      asphyxia. In this Series paper, we highlight some of the important advances in
      the understanding of how best to resuscitate newborn infants, which includes
      monitoring techniques to guide resuscitative efforts, increasing awareness of the
      adverse effects of hyperoxia, delayed umbilical cord clamping, the avoidance of
      routine endotracheal intubation for extremely preterm infants, and therapeutic
      hypothermia for hypoxic-ischaemic encephalopathy. Despite the challenges of
      performing high-quality clinical research in the delivery room, researchers
      continue to refine and advance our knowledge of effective resuscitation of
      newborn infants through scientific experiments and clinical trials.

PMID- 28443559
TI  - The evolution of modern respiratory care for preterm infants.
AB  - Preterm birth rates are rising, and many preterm infants have breathing
      difficulty after birth. Treatments for infants with prolonged breathing
      difficulty include oxygen therapy, exogenous surfactant, various modes of
      respiratory support, and postnatal corticosteroids. In this Series paper, we
      review the history of neonatal respiratory care and its effect on long-term
      outcomes, and we outline the future direction of the research field. The delivery
      and monitoring of oxygen therapy remains controversial, despite being in use for
      more than 50 years. Exogenous surfactant replacement has been used for 25 years
      and has dramatically reduced mortality and morbidity, but more research on when
      and how it is administered is needed. Methods and techniques of neonatal
      respiratory support are evolving. Clinicians are moving away from routine
      intubation and ventilation, and new modes of non-invasive support are being
      investigated. Postnatal corticosteroids have a limited role in infants with
      evolving bronchopulmonary dysplasia, but more research is needed to identify the
      best timing, type, dose, and method of administration. Despite advances in
      neonatal care in the past 50 years, bronchopulmonary dysplasia, with all its
      adverse short-term and long-term consequences, is still a serious problem in
      neonatal care. The challenge remains to support breathing in preterm infants,
      with special attention to risk factors in the subpopulation of infants that are
      at highest risk of bronchopulmonary dysplasia, without damaging their lungs or
      adversely affecting their long-term health.

PMID- 28443560
TI  - Advances in nutrition of the newborn infant.
AB  - Nutrition of newborn infants, particularly of those born preterm, has advanced
      substantially in recent years. Extremely preterm infants have high nutrient
      demands that are challenging to meet, such that growth faltering is common.
      Inadequate growth is associated with poor neurodevelopmental outcomes, and
      although improved early growth is associated with better cognitive outcomes,
      there might be a trade-off in terms of worse metabolic outcomes, although the
      contribution of early nutrition to these associations is not established. New
      developments include recommendations to increase protein supply, improve
      formulations of parenteral lipids, and provide mineral supplements while
      encouraging human milk feeding. However, high quality evidence of the risks and
      benefits of these developments is lacking. Clinical trials are also needed to
      assess the effect on preterm infants of experiencing the smell and taste of milk,
      to determine whether boys and girls should be fed differently, and to test
      effects of insulin and IGF-1 supplements on growth and developmental outcomes.
      Moderate-to-late preterm infants have neonatal nutritional challenges that are
      similar to those infants born at earlier gestations, but even less high quality
      evidence exists upon which to base clinical decisions. The focus of research in
      nutrition of infants born at term is largely directed at new formula products
      that will improve cognitive and metabolic outcomes. Providing the most effective
      nutrition to preterm infants should be prioritised as an important focus of
      neonatal care research to improve long-term metabolic and developmental outcomes.

PMID- 28443561
TI  - Turkey's Epidemiological and Demographic Transitions: 1931-2013.
AB  - BACKGROUND: The causes of death have changed with regard to the epidemiological
      and demographic events in society. There is no evidence of prior research into
      the epidemiological transition in Turkey. This transition in Turkey should be
      observed starting with the Ottoman Empire period (19th to early 20th century).
      However, information about the Ottoman Empire is quite limited. AIMS: To discuss
      the epidemiological and demographic transitions in Turkey, using demographic,
      educational and urbanization data in our present study. STUDY DESIGN: A
      descriptive archive study. METHODS: Mortality statistics dating from 1931 and
      published by the Turkish Statistical Institute were analysed, and the causes of
      death were coded and classified according to ICD-10. Other data were obtained
      from the published reports and studies regarding the issue. RESULTS: In the
      1930s, Turkey's life expectancy was low (aged 40 years), fertility and mortality
      rates were high (respectively 45% and 31%), and the main causes of death were
      infectious diseases. Nowadays, life expectancy is close to 80 years, the total
      fertility rate has dropped to 2.1 per woman, and the main causes of death are
      chronic diseases and cancer. The population rate in the urban areas has increased
      steadily from 24.2% in 1927 to 77.3% in 2012. level of education has also
      increased during this period. In 1935, less than 10% of women were literate, and
      in 2013 90% were literate. Qualitative and quantitative increase have been
      observed in the presentation and access of healthcare services compared to the
      early years of the Republic. CONCLUSION: Turkey has been undergoing a
      modernization period in the last 200 years, and it is believed that the
      epidemiological and demographic transitions result from this period. This process
      has led to urbanization and an increase in the level of education, as well as a
      decrease in premature deaths, lower fertility rates, and an increase in the
      elderly population and chronic diseases. It is therefore our conclusion that
      Turkey needs policies regarding the elderly population and the management of
      chronic diseases.

PMID- 28443562
TI  - Increased Risk of Metabolic Syndrome in Patients with Vitiligo.
AB  - BACKGROUND: Inflammatory and immune processes can be triggered in vitiligo due to
      a decreased number of melanocytes and their anti-inflammatory effects. Because of
      the systemic nature of vitiligo, metabolic abnormalities such as insulin
      resistance and lipid profile disturbances as well as skin involvement may be
      observed in vitiligo. AIMS: To investigate the association between metabolic
      syndrome and vitiligo. STUDY DESIGN: Case-control study. METHODS: The
      demographic, clinical and laboratory features in the subjects were compared
      according to presence of vitiligo and metabolic syndrome [patients (n=63) vs.
      gender-age matched controls (n=65) and metabolic syndrome positive (n=38) vs.
      negative (n=90)]. A logistic regression analysis was also used. RESULTS: We
      identified metabolic syndrome in 24 (38.1%) subjects with vitiligo and 14 (21.5%)
      subjects without vitiligo (p=0.04). Active vitiligo, segmental vitiligo, an
      increased duration of vitiligo and an increased percentage in the affected body
      surface area were determined to be independent predictors of metabolic syndrome
      [activity of vitiligo: p=0.012, OR (95% CI)=64.4 (2.5-1672); type of vitiligo:
      p=0.007, OR (95% CI)=215.1 (4.3-10725.8); duration of vitiligo: p=0.03, OR (95%
      CI)=1.4 (1.1-2.0); percentage of affected body surface area: p=0.07, OR (95%
      CI)=1.2 (0.98-1.5)]. CONCLUSION: The risk of developing metabolic syndrome is
      increased in patients with vitiligo. The poor clinical features of vitiligo, such
      as active, extended and segmental vitiligo with an increased duration of time,
      are independent predictors for developing metabolic syndrome.

PMID- 28443563
TI  - Non-thrombotic Pulmonary Embolism Due to Liver Hydatic Cyst: A Case Report.
AB  - BACKGROUND: A non-thrombotic pulmonary embolism is defined as embolization to the
      pulmonary circulation. It may be caused by microorganisms, foreign bodies,
      different cell types or gas in the pulmonary circulation. Pulmonary hydatid cyst
      induced embolization is a rare complication of heart or liver hydatid cysts. CASE
      REPORT: We describe the fatal case of a 15-year-old boy without any known prior
      illness who was admitted to the hospital after feeling unwell and dropping to the
      ground while playing ball. During the autopsy, a lesional mass, with dimensions
      of 13x6 cm, was observed in the left lobe of the liver. The histomorphological
      examination of pulmonary sections showed scolices observed in pulmonary vessel
      lumina, thus a non-thrombosis hydatid embolism was diagnosed. Based on the
      findings, the cause of death was recorded as a non-thrombotic hydatid embolism.
      CONCLUSION: The present case is interesting because a non-thrombotic pulmonary
      embolism rarely results in sudden death, and a definitive diagnosis was possible
      only by a histopathological examination.

PMID- 28443564
TI  - Transpulmonary Hypothermia with Cooled Oxygen Inhalation Shows Promising Results
      as a Novel Hypothermia Technique.
AB  - BACKGROUND: Therapeutic hypothermia was showed to improve neurologic outcome but
      current therapeutic hypothermia techniques have limitations. Novel techniques
      such as transpulmonary hypothermia with cooled oxygen inhalation may be
      beneficial. AIMS: To evaluate the performance of transthoracic hypothermia with
      cooled medical oxygen inhalation as a therapeutic hypothermia method. STUDY
      DESIGN: Animal experimentation. METHODS: A total of 36 adult male Wistar-Hannover
      rats were used in this research. Rats were randomised into four groups: group 1,
      Cooled oxygen group; group 2, IV cold fluid group; group 3, Surface cooling
      group; group 4, control group. No hypothermia method was applied in the control
      group. Hypothermia techniques were administered in the other three groups until
      the targeted core temperature was maintained. The target temperature was
      continued for one hour at 32-34  degrees C. After that, rats were heated up with
      hot blankets. Once the rectal temperature reached 38  degrees C, rats were
      euthanised. The main outcomes were the rate of temperature decrease ( degrees C
      per minute) (S) and the time required to reach the target body temperature (T).
      RESULTS: All rats survived the study protocol. When compared to the control
      group, T and S values were better in the cooled medical oxygen inhalation group
      (p<0.001). The IV cold fluid group had lower S values and higher T values
      compared to the cooled oxygen group (p<0.001, and p=0.003, respectively). There
      was no meaningful pathology in the histological samples in any group. CONCLUSION:
      As an easy-to-use and inexpensive method, cooled oxygen inhalation may be a
      beneficial hypothermia technique.

PMID- 28443566
TI  - Atypical Chemokine Receptor 1 Polymorphism can not Affect Susceptibility to
      Hepatitis C Virus.
AB  - BACKGROUND: Hepatitis C virus has infected 130 to 150 million individuals
      globally. Atypical chemokine receptor 1 has become a focus of research because of
      its diverse roles in different diseases. However, little is known regarding the
      association of atypical chemokine receptor 1 polymorphism with susceptibility to
      hepatitis C virus. AIMS: To determine the association of an atypical chemokine
      receptor 1 polymorphism (rs12075) with hepatitis C virus susceptibility. STUDY
      DESIGN: Case-control study. METHODS: We collected blood samples from 231 patients
      infected with hepatitis C virus and 239 blood donors as control subjects.
      Genotyping of atypical chemokine receptor 1 was performed using a 5'-nuclease
      assay with TaqMan-minor groove binding probes. Comparisons between hepatitis C
      virus-infected patients and control subjects were assessed using Fisher's exact
      test. RESULTS: The genotype frequencies of FY*A/FY*A, FY*A/FY*B and FY*B/FY*B
      were 86.1%, 13.9% and 0% in the patient group, and 86.2%, 13.4% and 0.4% in the
      control group, respectively. The difference in atypical chemokine receptor 1
      genotype frequencies between hepatitis C virus-infected patients and control
      group was not significant (p=1.00, OR=1.004, 95% CI=0.594-1.695). FY*A and FY*B
      allele frequencies were 93.1% and 6.9% in the patient group, and 92.9% and 7.1%
      in the control group, respectively. The difference in atypical chemokine receptor
      1 allele frequencies between hepatitis C virus-infected patients and the control
      group was not significant (p=1.00, OR=0.972, 95% CI=0.589-1.603). CONCLUSION: Our
      result indicates that atypical chemokine receptor 1 polymorphism (rs12075) does
      not affect susceptibility to hepatitis C virus.

PMID- 28443565
TI  - Influenza and Pneumonia Vaccination Rates and Factors Affecting Vaccination among
      Patients with Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: Influenza and pneumococcal vaccinations are recommended in chronic
      obstructive pulmonary disease patients to decrease associated risks at all
      stages. Although the prevalence of chronic obstructive pulmonary disease is high
      in our country, as previously reported, vaccination rates are low. AIMS: To
      assess the vaccination rates of chronic obstructive pulmonary disease patients
      and factors that may affect these. STUDY DESIGN: Multi-centre cross-sectional
      study. METHODS: Patients admitted to the chest diseases clinics of six different
      centres between 1 February 2013 and 1 January 2014 with a pre-diagnosis of
      Chronic obstructive pulmonary disease according to the Global initiative for
      chronic obstructive lung disease criteria, who were in a stable condition were
      included in the study. The survey, which included demographic characteristics,
      socio-economic status, severity of disease and vaccination information, was first
      tested on a small patient population before the study. The survey was completed
      by the investigators after obtaining written informed consent. RESULTS: The
      average age of the 296 included patients was 66.3+/-9.3 years and 91.9% were
      male. Of these, 36.5% had the influenza vaccination and 14.1% had the
      pneumococcal vaccination. The most common reason for not being vaccinated was 'no
      recommendation by doctors': 57.2% in the case of influenza vaccinations, and
      46.8% in the case of pneumococcal vaccinations. Both vaccination rates were
      significantly higher in those patients with comorbidities (influenza vaccination
      p<0.001; pneumococcal vaccination p=0.06). There was no significant correlation
      with age, gender, smoking and severity of disease (p>0.05). Vaccination rates
      were significantly higher in those with a white-collar occupation and higher
      education level, and who presented to a university hospital (p<0.001).
      CONCLUSION: Medical professionals do not request vaccinations as often as the
      International Guidelines suggest for chronic obstructive pulmonary disease
      patients. Awareness of the importance of these vaccinations among both doctors
      and patients needs to be addressed.

PMID- 28443567
TI  - Association Between the Inflammatory Biomarkers and Left Ventricular Systolic
      Dysfunction in Patients with Exacerbations of Chronic Obstructive Pulmonary
      Disease.
AB  - BACKGROUND: Cardiovascular diseases are an important cause of morbidity and
      mortality in chronic obstructive pulmonary disease patients. The increased
      inflammatory biomarker levels predict exacerbations and are associated with
      cardiovascular diseases in stable chronic obstructive pulmonary disease patients
      but their role in the settings of acute chronic obstructive pulmonary disease
      exacerbations has not been determined. AIMS: To analyse the association between
      inflammatory biomarkers and heart failure and also to determine the predictors of
      mortality in patients with exacerbations of chronic obstructive pulmonary
      disease. STUDY DESIGN: Prospective observational study. METHODS: We analysed 194
      patients admitted for acute exacerbation of chronic obstructive pulmonary disease
      at The Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia.
      In all patients, C-reactive protein, fibrinogen, N-terminal of the pro-hormone
      brain natriuretic peptide and white blood count were measured and transthoracic
      echocardiography was performed. RESULTS: There were 119 men (61.3%) and the
      median age was 69 years (interquartile range 62-74). Left ventricular systolic
      dysfunction (ejection fraction <50%) was present in 47 (24.2%) subjects. Patients
      with left ventricular systolic dysfunction had higher C-reactive protein levels
      (median 100 vs. 31 mg/L, p=0.001) and fibrinogen (median 5 vs. 4 g/L, p=<0.001)
      compared to those with preserved ejection fraction. The overall hospital
      mortality was 8.2% (16/178). The levels of C-reactive protein, fibrinogen, N
      terminal pro-brain natriuretic peptide and ejection fraction predicted hospital
      mortality in univariate analysis. After adjusting for age, hypoxemia and C
      reactive protein, ejection fraction remained significant predictors of hospital
      mortality (OR 3.89, 95% CI 1.05-15.8). CONCLUSION: Nearly a quarter of patients
      with the exacerbation of chronic obstructive pulmonary disease present with left
      ventricular systolic dysfunction which may be associated with mortality.

PMID- 28443568
TI  - The Compartment Syndrome Associated with Deep Vein Thrombosis due to Rattlesnake
      Bite: A Case Report.
AB  - BACKGROUND: Snakebite is a health issue specific to some parts of the world,
      especially in the tropical areas, where it produces many victims. The main
      clinical damage caused by snakebite involves haemotoxic, neurotoxic and myotoxic
      reactions. We report the case of a young woman suffering from snakebite who
      developed deep vein thrombosis and compartment syndrome. CASE REPORT: We present
      the case of a 32-year-old Romanian woman who was injured by her own Crotalinae
      snake (also known as pit viper or rattlesnake) on her left forearm. When admitted
      to our Emergency Department, she was conscious with a Glasgow coma scale of
      12/15, somnolent, febrile, suffering of headache, tachypnoea; the marks of the
      snakebite were located in the distal part of the anterior left forearm; she had
      pain and bleeding at the bite site and swelling of the left upper limb with
      lymphangitis up to the axilla. She experienced fasciotomy-requiring compartment
      syndrome of the upper limb and required unfractionated heparin and close
      monitoring using activated partial thromboplastin time evolution due to micro
      thrombosis in the brachial vein. Local improvement was achieved in the next 4
      days with progressive diminishment of local tenderness and swelling. CONCLUSION:
      Limb deep vein thrombosis might be induced by snakebite, despite the pro
      haemorrhagic general condition induced by the envenomation. A high index of
      clinical suspicion is needed for early diagnosis and timely management, which can
      improve survival of these patients.

PMID- 28443570
TI  - Management of Forgotten Ureteral Stents: Relationship Between Indwelling Time and
      Required Treatment Approaches.
AB  - BACKGROUND: Double-J stents are widely used in urology practice, and removal of
      these stents can sometimes be forgotten. AIMS: To investigate whether indwelling
      time of double-J stent can predict which treatment modality is required for
      removal of the stent from the body. STUDY DESIGN: A multicentre, retrospective
      observational study. METHODS: The data of 57 patients who were treated for
      forgotten ureteral stents between January 2007 and December 2014 were evaluated
      retrospectively. Patients were classified into four groups according to
      indwelling time of the stents: 6-12 months, 13-24 months, 25-36 months, and <36
      months. Encrustation and associated stone burden of the stents were evaluated
      with non-contrast stone protocol computerised tomography. RESULTS: Patients were
      classified according to their duration of the stent indwelling time. Simple
      cystoscopic stent retrieval was performed in 71.4% of patients in the 6-12 months
      group, 44% of patients in the 13-24 months group, 6.2% of patients in the 25-36
      months group, and 11.1% of patients in the <36 months group. A percutaneous or
      open surgery was required in no patients with an indwelling time of double-J
      stent shorter than 30 months. CONCLUSION: Transurethral and/or percutaneous
      combined endo-urological approaches are usually sufficient for the removal of
      forgotten double-J stents. Transurethral procedures are sufficient for the
      treatment of patients with double-J stent indwelling times less than 30 months.

PMID- 28443569
TI  - Can a Small Intestine Segment Be an Alternative Biological Conduit for Peripheral
      Nerve Regeneration?
AB  - BACKGROUND: Autologous nerve grafts are used to bridge peripheral nerve defects.
      Limited sources and donor site morbidity are the major problems with peripheral
      nerve grafts. Although various types of autologous grafts such as arteries, veins
      and muscles have been recommended, an ideal conduit has not yet been described.
      AIMS: To investigate the effectiveness of a small intestinal conduit for
      peripheral nerve defects. STUDY DESIGN: Animal experimentation. METHODS: Twenty
      one rats were divided into three groups (n=7). Following anaesthesia, sciatic
      nerve exploration was performed in the Sham group. The 10 mm nerve gap was
      bridged with a 15 mm ileal segment in the small intestinal conduit group and the
      defect was replaced with orthotopic nerve in autologous nerve graft group. The
      functional recovery was tested monthly by walking-track analysis and the sciatic
      functional index. Histological evaluation was performed on the 12th week.
      RESULTS: Sciatic functional index tests are better in autologous nerve graft
      group (-55.09+/-6.35); however, during follow-up, progress in sciatic functional
      index was demonstrated, along with axonal regeneration and innervation of target
      muscles in the small intestinal conduit group (-76.36+/-12.08) (p<0.05). In
      histologic sections, distinctive sciatic nerve regeneration was examined in the
      small intestinal conduit group. The expression of S-100 and neurofilament was
      observed in small intestinal conduit group but was less organised than in the
      autologous nerve graft group. Although the counted number (7459.79+/-1833.50 vs.
      4226.51+/-1063.06 mm2), measured diameter [2.19 (2.15-2.88) vs. 1.74 (1.50-2.09)
      um] and myelin sheath thickness [1.18 (1.09-1.44) vs. 0.66 (0.40-1.07) um] of
      axons is significantly high in the middle sections of autologous nerve graft
      compared to the small intestinal conduit group, respectively (p<0.05), the
      peripheral nerve regeneration was also observed in the small intestinal conduit
      group. CONCLUSION: Small intestinal conduit should not be considered as an
      alternative to autologous nerve grafts in its current form; however, the results
      are promising. Even though the results are no better than autologous nerve
      grafts, with additional procedures, it might be a good alternative due to
      harvesting abundant sources without donor site morbidity.

PMID- 28443571
TI  - Numerical Optimization of the Position in Femoral Head of Proximal Locking Screws
      of Proximal Femoral Nail System; Biomechanical Study.
AB  - BACKGROUND: Proximal femoral fracture rates are increasing due to osteoporosis
      and traffic accidents. Proximal femoral nails are routinely used in the treatment
      of these fractures in the proximal femur. AIMS: To compare various combinations
      and to determine the ideal proximal lag screw position in pertrochanteric
      fractures (Arbeitsgemeinschaft fur Osteosynthesefragen classification 31-A1) of
      the femur by using optimized finite element analysis. STUDY DESIGN: Biomechanical
      study. METHODS: Computed tomography images of patients' right femurs were
      processed with Mimics. Afterwards a solid femur model was created with SolidWorks
      2015 and transferred to ANSYS Workbench 16.0 for response surface optimization
      analysis which was carried out according to anterior-posterior (-10 degrees
      <anterior-posterior<10 degrees ), inferior-superior (-6 degrees <inferior
      superior<7 degrees ) and tip-apex distance (10 mm<tip-apex distance<30 mm)
      proximal lag screw positions in the fracture region. The optimum position of the
      proximal lag screw was determined based on the von Mises stress values occurring
      on the fracture line. Initial analysis of the system was realized under the
      surgeon's normal positioning conditions (anterior-posterior, inferior-superior=0
      degrees ; tip-apex distance=12 mm). RESULTS: The maximum and minimum
      (compression) von Mises stresses were found to be 438 MPa and 0.003 MPa,
      respectively, and risky stresses for the system occurred in the regions where the
      proximal lag screw passes through the proximal femoral nail hole, the small
      diameter portion of stem joints with a large diameter and lag screw mounts to the
      stem. The most suitable position of the proximal lag screw was found at the
      middle position of the tip-apex distance (20 mm) and femoral neck (anterior
      posterior, inferior-superior=0 degrees ), according to von Mises compression
      stress values occurring on the fracture line. CONCLUSION: In our study, we
      couldn't find any correlation between proximal lag screw movement and tip-apex
      distance on stresses of the fracture surfaces, but the proximal lag screw
      position in the inferior (inferior-superior<0)-superior (inferior-superior>0) and
      posterior-anterior directions of the femur neck significantly increased these
      stresses. The most suitable position of the proximal lag screw was confirmed as
      the middle of the femoral neck by using optimized finite element analysis.

PMID- 28443572
TI  - Primary Sinonasal Malignant Melanoma: Effect of Clinical and Histopathologic
      Prognostic Factors on Survival.
AB  - BACKGROUND: Mucosal melanoma is a rare malignancy arising from melanocytes of the
      mucosal surfaces. The pattern and frequency of oncogenic mutations and
      histopathological biomarkers have a role on distinct tumour behaviour and
      survival. AIMS: To assess the rate of C-KIT positivity and its effect on survival
      of surgically treated sinonasal malignant melanoma patients with other
      histopathological biomarkers and clinical features. STUDY DESIGN: Retrospective
      cross-sectional study. METHODS: Seventeen sinonasal malignant melanoma patients
      with a mean age of 65.41 (39-86) years were included. Overall survival and
      disease-specific survival rates were calculated. The impact of age, gender, stage
      and extent of the disease, type of surgery, and adjuvant therapies were also
      taken into consideration. The effect of mitotic index, pigmentation, S100, HMB
      45, Melan-A and C-KIT on survival were evaluated. RESULTS: Median tumour size was
      20 mm (interquartile range=27.5 mm). Pigmentation was present in 7 (41.2%) cases.
      Median number of mitoses per millimetre squared was 11 (interquartile range=13).
      Melan A was positive in 7 (41.2%) patients, ulceration was present in 6 cases
      (35.3%), and necrosis was present in (47.1%) 8 cases. Six patients (35.3%) were
      positive for S100, 14 (82.4%) specimens stained positive for HMB-45 and C-KIT
      (CD117) was positive in 9 cases (52.9%). Three patients (16.7%) developed distant
      metastasis. Five year overall and disease free survival rates were 61.4% and
      43.8%, respectively. CONCLUSION: Although C-KIT positive sinonasal malignant
      melanoma patients (52.9%) can be candidates for targeted tumour therapies, the
      studied clinical or histopathological features along with C-KIT seem to have no
      significant effect on survival in a small group of patients with sinonasal
      malignant melanoma.

PMID- 28443573
TI  - Normal and Tumour Tissue mRNA Expressions of Telomerase Complex Genes in Several
      Types of Cancer.
AB  - AIMS: To investigate the changes in mRNA expression levels of telomerase-related
      significant proteins in several types of cancer. METHODS: Human telomerase
      reverse transcriptase, pontin, reptin and dyskerin expressions were measured in
      normal and tumour tissues obtained from 26 patients with colorectal, breast and
      gastric cancers, using the real-time reverse transcriptase-polymerase chain
      reaction method. RESULTS: For all patients, no significant difference was found
      in mRNA expressions of human telomerase reverse transcriptase and dyskerin
      (p>0.05), although their levels in tumour tissues were found to be higher than in
      normal tissues. However, pontin and reptin mRNA expressions were significantly
      higher in tumour tissues than in normal tissues (p<0.01). While human telomerase
      reverse transcriptase showed a high correlation with only pontin (p<0.001) in
      normal tissues, high positive correlations were observed between human telomerase
      reverse transcriptase with pontin (p<0.005), reptin (p<0.01) and dyskerin
      (p<0.01) in tumour tissues. CONCLUSION: The increased mRNA expressions of all
      four genes in tumour tissues may suggest a role in cancer development.
      Correlations of pontin, reptin and dyskerin with human telomerase reverse
      transcriptase support the hypotheses describing their roles in telomerase
      complexes.

PMID- 28443574
TI  - Parents' Attitudes and Adherence to Unintentional Injury Prevention Measures in
      Ankara, Turkey.
AB  - BACKGROUND: Childhood unintentional injuries are perceived as a leading public
      health issue since they are one of the preventable causes of paediatric mortality
      and morbidity. Whether and how parental factors are related to childhood injury
      has been researched insufficiently. AIMS: To investigate parents' attitudes to
      preventive measures of unintentional childhood injury, and the parental adherence
      to these measures. STUDY DESIGN: Cross-sectional, descriptive study. METHODS: The
      data were collected from the parents of children younger than ten years of age
      admitted to university hospital outpatient clinics for any reason and who agreed
      to be involved in the study. The first part of the questionnaire included
      sociodemographic profiles of participating children. Serious injuries were
      considered to be any injury that requires hospital admission. The second part of
      the questionnaire was prepared to evaluate parents' adherence to injury
      prevention rules. A total score calculation about the adherence of the parents to
      the injury prevention rules was worked out the addition of the scores of each
      answer given in each age group. Answers for each item given by the parents were
      scored as wrong (0), sometimes (1) or correct (2). The score for each item was
      added and the result normalized to 100 points. Only complete questionnaires were
      used for analysis. RESULTS: A total of 1126 children and parent pairs agreed to
      participate in the survey. It was found that 13.8% of the participating children
      had experienced at least one serious injury. Although three-quarters of the
      parents had received information about injury prevention, the overall injury
      prevention scores were found to be low. As children's age increased, the total
      injury prevention scores of parents decreased significantly. Injury prevention
      scores were shown to increase significantly with high education and maternal
      occupation. However, scores were shown to decrease significantly with increased
      child age and family size. CONCLUSION: Our study shows that parental adherence to
      the child safety measures aimed at decreasing the unintentional injury risk of
      children is not satisfactory in Turkey. In particular, parents of 5-9-year-old
      children, big families (more than five people), parents with less than 8 years of
      education and non-working mothers should be the main target groups for
      intervention strategies according to our study results.

PMID- 28443575
TI  - The Time in Therapeutic Range and Bleeding Complications of Warfarin in Different
      Geographic Regions of Turkey: A Subgroup Analysis of WARFARIN-TR Study.
AB  - BACKGROUND: The time in therapeutic range values may vary between different
      geographical regions of Turkey in patients vitamin K antagonist therapy. AIMS: To
      evaluate the time in therapeutic range percentages, efficacy, safety and
      awareness of warfarin according to the different geographical regions in patients
      who participated in the WARFARIN-TR study (The Awareness, Efficacy, Safety and
      Time in Therapeutic Range of Warfarin in the Turkish population) in Turkey. STUDY
      DESIGN: Cross-sectional study. METHODS: The WARFARIN-TR study includes 4987
      patients using warfarin and involved regular international normalized ratio
      monitoring between January 1, 2014 and December 31, 2014. Patients attended
      follow-ups for 12 months. The sample size calculations were analysed according to
      the density of the regional population and according to Turkish Statistical
      Institute data. The time in therapeutic range was calculated according to F.R.
      Roosendaal's algorithm. Awareness was evaluated based on the patients' knowledge
      of the effect of warfarin and food-drug interactions with simple questions
      developed based on a literature review. RESULTS: The Turkey-wide time in
      therapeutic range was reported as 49.5%+/-22.9 in the WARFARIN-TR study. There
      were statistically significant differences between regions in terms of time in
      therapeutic range (p>0.001). The highest rate was reported in the Marmara region
      (54.99%+/-20.91) and the lowest was in the South-eastern Anatolia region (41.95+/
      24.15) (p>0.001). Bleeding events were most frequently seen in Eastern Anatolia
      (41.6%), with major bleeding in the Aegean region (5.11%) and South-eastern
      Anatolia (5.36%). There were statistically significant differences between the
      regions in terms of awareness (p>0.001). CONCLUSION: Statistically significant
      differences were observed in terms of the efficacy, safety and awareness of
      warfarin therapy according to different geographical regions in Turkey.

PMID- 28443577
TI  - Aretaeus of Cappadocia and Pulmonary Tuberculosis.

PMID- 28443576
TI  - Changes in Bacterial Resistance Patterns of Pediatric Urinary Tract Infections
      and Rationale for Empirical Antibiotic Therapy.
AB  - BACKGROUND: The causative agent spectrum and resistance patterns of urinary tract
      infections in children are affected by many factors. AIMS: To demonstrate
      antibiotic resistance in urinary tract infections and changing ratio in
      antibiotic resistance by years. STUDY DESIGN: Retrospective cross-sectional
      study. METHODS: We analysed antibiotic resistance patterns of isolated Gram (-)
      bacteria during the years 2011-2014 (study period 2) in children with urinary
      tract infections. We compared these findings with data collected in the same
      centre in 2001-2003 (study period 1). RESULTS: Four hundred and sixty-five
      uncomplicated community-acquired Gram (-) urinary tract infections were analysed
      from 2001-2003 and 400 from 2011-2014. Sixty-one percent of patients were female
      (1.5 girls : 1 boy). The mean age of children included in the study was 3 years
      and 9 months. Escherichia coli was the predominant bacteria isolated during both
      periods of the study (60% in study period 1 and 73% in study period 2). Bacteria
      other than E. coli demonstrated a higher level of resistance to all of the
      antimicrobials except trimethoprim-sulfamethoxazole than E. coli bacteria during
      the years 2011-2014. In our study, we found increasing resistance trends of
      urinary pathogens for cefixime (from 1% to 15%, p<0.05), amikacin (from 0% to 4%,
      p<0.05) and ciprofloxacin (from 0% to 3%, p<0.05) between the two periods.
      Urinary pathogens showed a decreasing trend for nitrofurantoin (from 17% to 7%,
      p=0.0001). No significant trends were detected for ampicillin (from 69% to 71%),
      amoxicillin-clavulanate (from 44% to 43%), cefazolin (from 39% to 32%),
      trimethoprim-sulfamethoxazole (from 32% to 31%), cefuroxime (from 21% to 18%) and
      ceftriaxone (from 10% to 14%) between the two periods (p>0.05). CONCLUSION: In
      childhood urinary tract infections, antibiotic resistance should be evaluated
      periodically and empiric antimicrobial therapy should be decided according to
      antibiotic sensitivity results.

PMID- 28443578
TI  - Hyoid Bone and Thyroid Cartilage Metastases from Sigmoid Colon Adenocarcinoma: A
      Case Report.
AB  - BACKGROUND: Secondary tumours of the hyoid bone and thyroid cartilage are
      extremely rare. In this paper, we present a case of the hyoid bone and thyroid
      cartilage metastases in a patient treated for sigmoid colon adenocarcinoma. CASE
      REPORT: Four years after sigmoid colon adenocarcinoma was diagnosed and treated
      with surgery and chemotherapy, the patient developed bone metastases in the left
      sacroiliac joint and right proximal humerus. Although the patient did not
      complain of any related symptoms, in a bone scintigraphy the accumulation of
      Technetium-99m was incidentally detected in the two sites of the anterior neck.
      On ultrasound examination there were two hyperechoic and heterogeneous masses
      with calcifications placed in front of the hyoid bone and thyroid cartilage.
      Computerized tomography demonstrated massive hyoid bone and thyroid cartilage
      destruction. CONCLUSION: In patients with progressive sigmoid colon
      adenocarcinoma, destruction of the hyoid bone and thyroid cartilage could be
      suspected for metastases.

PMID- 28443579
TI  - Determining the Efficiency of Different Preoperative Difficult Intubation Tests
      on Patients Undergoing Caesarean Section.
AB  - BACKGROUND: Pregnancy-induced anatomical and physiological changes in the airway
      make airway management difficult in obstetric patients; thus, preoperative
      evaluation of the airway is important for obstetric patients. AIMS: To determine
      the effectiveness of the modified Mallampati test; the interincisor, sternomental
      and thyromental distances and the upper limb bite test. The second aim was to
      assess the effectiveness of the combination of the upper limb bite test with the
      other tests in obstetric patients. STUDY DESIGN: Cross-sectional study. METHODS:
      Pregnant women (n=250) scheduled for caesarean section were analysed. The
      patients' ages, heights and weights were collected. Preoperative airway
      evaluation was done by using a modified version of the Mallampati test. The
      interincisor, sternomental and thyromental distances were measured, and the upper
      limb bite test was performed. The laryngoscopy difficulty was evaluated by using
      Cormack-Lehane classification. RESULTS: No statistically significant differences
      were found between groups in age, height or weight (p>0.05). The modified
      Mallampati test and interincisor, sternomental and thyromental distances revealed
      a lower number of easy intubations than that determined by the Cormack-Lehane
      classification and a higher number of difficult intubations than the actual
      number of cases (p<0.05). The sensitivity and specificity of the modified
      Mallampati test, the upper limb bite test, the interincisor distance test and the
      sternomental and thyromental distance tests were found to be 73.08, 57.69, 84.62,
      80.77 and 88.46 and 90.62, 99.11, 83.04, 84.37 and 87.05, respectively. When the
      combinations were examined, the sensitivity and specificity of the combination of
      the upper limb bite test with the modified Mallampati test were found to be 57.69
      and 100, respectively. When the upper limb bite test was combined with the
      interincisor distance, the sensitivity and specificity were 46.15 and 100,
      respectively. We found a sensitivity and specificity of 93.75 and 95.30,
      respectively, for the combination of the upper limb bite test with the
      thyromental distance test. The sensitivity and specificity of the combination of
      the upper limb bite test with the modified Mallampati test and interincisor
      distance test were found to be 46.15 and 100, respectively. For combination of
      all the tests, the sensitivity and specificity was 42.31 and 100, respectively.
      CONCLUSION: When all combinations are evaluated in the decision of difficult
      intubation, the combination of the upper limb bite test and thyromental distance
      test is superior to the use of other methods alone to predict difficult
      intubation in pregnant women.

PMID- 28443580
TI  - Amyopathic Dermatomyositis Associated with Histopathological Findings of
      Organizing Pneumonia and Pulmonary Vasculitis.
AB  - BACKGROUND: Clinically, amyopathic dermatomyositis is a clinically distinct
      subgroup of dermatomyositis characterised by unique dermatological manifestations
      without muscle involvement. Clinically, amyopathic dermatomyositis is frequently
      associated with interstitial lung disease, which usually has a rapidly
      progressive, fatal clinical course. Although clinically, amyopathic
      dermatomyositis-related interstitial lung disease is well described, data on the
      histopathology of clinically, amyopathic dermatomyositis-interstitial lung
      disease are limited. Organising pneumonia and pulmonary vasculitis have rarely
      been reported. CASE REPORT: A 54-year-old Korean woman presented with exertional
      dyspnoea and a dry cough. Chest computed tomography revealed subpleural ground
      glass opacities suggesting interstitial lung disease, which was later
      pathologically confirmed to be a combination of organising pneumonia and
      pulmonary vasculitis. The patient improved markedly with prednisone treatment and
      has remained stable for a long time. CONCLUSION: We hereby report a rare
      combination of organising pneumonia and pulmonary vasculitis in a patient with
      amyopathic dermatomyositis-interstitial lung disease.

PMID- 28443581
TI  - Bocavirus Viremia and Hepatitis in an Immunocompetent Child.
AB  - BACKGROUND: So far, many studies have shown that Human Bocavirus ( HBoV) is the
      main pathogen of the respiratory tract. Until now, there is no study that proves
      the association between HBoV and hepatitis. HBoV viremia/DNAemia has been
      associated closely with acute primary infection and moderate-to-severe illness
      but, more detailed clinical data about HBoV dissemination are still unavailable.
      CASE REPORT: Here we report a 2-years-5-months-old girl suffering from
      respiratory distress and heptitis followed in our intensive care unit. HBoV was
      detected in our patients nose and throat swabs concurrent with whole blood sample
      by positive polymerase chain reactions. After a through investigation no
      causative agent other than HBoV viremia was found. CONCLUSION: Human Bocavirus
      viremia with high viral loads may be associated with hepatitis.

PMID- 28443582
TI  - High-Resolution Computed Tomography and Pulmonary Function Findings of
      Occupational Arsenic Exposure in Workers.
AB  - BACKGROUND: The number of studies where non-malignant pulmonary diseases are
      evaluated after occupational arsenic exposure is very few. AIMS: To investigate
      the effects of occupational arsenic exposure on the lung by high-resolution
      computed tomography and pulmonary function tests. STUDY DESIGN: Retrospective
      cross-sectional study. METHODS: In this study, 256 workers with suspected
      respiratory occupational arsenic exposure were included, with an average age of
      32.9+/-7.8 years and an average of 3.5+/-2.7 working years. Hair and urinary
      arsenic levels were analysed. High-resolution computed tomography and pulmonary
      function tests were done. RESULTS: In workers with occupational arsenic exposure,
      high-resolution computed tomography showed 18.8% pulmonary involvement. In
      pulmonary involvement, pulmonary nodule was the most frequently seen lesion
      (64.5%). The other findings of pulmonary involvement were 18.8% diffuse
      interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The
      mean age of patients with pulmonary involvement was higher and as they smoked
      more. The pulmonary involvement was 5.2 times higher in patients with skin
      lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was
      significantly lower in patients with pulmonary involvement. CONCLUSION: Besides
      lung cancer, chronic occupational inhalation of arsenic exposure may cause non
      malignant pulmonary findings such as bronchiectasis, pulmonary nodules and
      diffuse interstitial lung disease. So, in order to detect pulmonary involvement
      in the early stages, workers who experience occupational arsenic exposure should
      be followed by diffusion test and high-resolution computed tomography.

PMID- 28443583
TI  - Retrograde Cerebral Air Embolism in a Patient with Intestinal Necrosis: A Case
      Report.
AB  - BACKGROUND: Cerebral venous air embolism is a severe clinical condition related
      to an unfavourable outcome in patients with neurological impairment. Cerebral
      venous air embolism may occur secondarily to arterial or venous interventions. A
      rare mechanism of cerebral venous air embolism is retrograde embolism, which is
      characterized by gas flow in a direction that is opposite to that of the normal
      blood flow. CASE REPORT: A 69-year-old female was admitted to our hospital with
      shortness of breath and abdominal pain. Abdominal computed tomography revealed
      intramural gas in the bowel and free gas in the mesenteric veins and portal vein.
      Cranial computed tomography, which was performed due to impaired consciousness,
      demonstrated cerebral air embolism with the appearance of a gyriform pattern. A
      bedside echocardiography and chest computed tomography revealed no evidence of
      right-to-left shunt. CONCLUSION: Cerebral venous air embolism may occur after
      pneumatosis intestinalis by a retrograde flow of air from the mesenteric veins
      and portal vein. Low cardiac output and supine position are contributing factors
      for a retrograde flow of air bubbles into the venous circulation of the brain.

PMID- 28443584
TI  - Is the Diagnosis of Celiac Disease Possible Without Intestinal Biopsy?
AB  - BACKGROUND: Coeliac disease is defined as a state of immune-mediated hyper
      responsiveness to dietary gluten from wheat, barley, or rye in genetically
      predisposed individuals that results in tissue damage. The diagnosis is made by
      microscopic examination of a small intestinal biopsy, although serological
      testing for antibodies against tissue transglutaminase and deamidated gliadin
      peptide can be of great advantage. It has been suggested that duodenal biopsy can
      be avoided in patients with high levels of the tissue transglutaminase antibody,
      since a relationship has been found to be present between tissue transglutaminase
      antibody titres and coeliac disease. AIMS: To study the correlation between
      tissue transglutaminase titre and small intestinal biopsy findings in patients
      with coeliac disease. STUDY DESIGN: Diagnostic accuracy study. METHODS: Ninety
      five cases of patients diagnosed with coeliac disease and with positive serum
      tissue transglutaminase titres were retrieved from the Jordan University Hospital
      archives between December 2014 and December 2015. All the cases were classified
      according to the Marsh classification. RESULTS: Ninety-five cases with a positive
      titre for the antibody were included in this study, 73 (76.8%) of them were
      females and 22 cases (23.2%) were males. The age of the patients ranged between 4
      and 75 years with a mean age +/- standard deviation of 32.3+/-14.7. The
      sensitivity was the highest in Marsh IIIC and lowest in Marsh IIIA (95% versus
      68% respectively). The specificity was moderate (76%) for all subtypes of Marsh
      III. CONCLUSION: This study showed a positive correlation between the tissue
      transglutaminase titre and the degree of duodenal damage (Marsh IIIC) in patients
      with coeliac disease. In the presence of high tissue transglutaminase levels,
      duodenal biopsy might not be always necessary for diagnosis, particularly in
      symptomatic patients.

PMID- 28443586
TI  - Salmonella enterica Serovar Enteritidis Liver Abscess after Blunt Abdominal
      Trauma.
AB  - BACKGROUND: Salmonella enterica serovar Enteritidis is among the most reported
      serotypes of Salmonella species worldwide, but is rarely reported as the
      causative agent of a liver abscess. CASE REPORT: We present a patient with an
      abdominal blunt trauma. An initial abdominal computed tomography scan revealed a
      rupture of the right kidney and of the liver. Two days later, his physical state
      deteriorated and a new computed tomography scan was obtained. An extremely large
      8-centimetre liver abscess was verified. Due to the unsatisfying response to
      antibiotic therapy and percutaneous drainage, we operated on the patient. An
      appendectomy, cholecystectomy and bisegmental liver resection were performed. An
      intraoperative swab from the abscess was positive for Salmonella enterica serovar
      Enteritidis. The patient was given intravenous ciprofloxacine. The post-operative
      course was complicated by a Coagulase-negative Staphylococcus infection of the
      wound, which improved with antibiotic therapy. CONCLUSION: Blunt abdominal trauma
      may initiate an unpredictable course of the disease in chronic Salmonella
      carriers.

PMID- 28443587
TI  - Role of Trace Elements for Oxidative Status and Quality of Human Sperm.
AB  - BACKGROUND: Oxidative stress affects sperm quality negatively. To maintain the
      pro/antioxidant balance, some metal ions (e.g. copper, zink, iron, selenium),
      which are co-factors of the antioxidant enzymes, are essential. However, iron and
      copper could act as prooxidants inducing oxidative damage of spermatozoa. AIMS:
      To reveal a possible correlation between the concentrations of some metal ions
      (iron, copper, zinc, and selenium) in human seminal plasma, oxidative stress,
      assessed by malondialdehyde and total glutathione levels, and semen quality,
      assessed by the parameters count, motility, and morphology. STUDY DESIGN:
      Descriptive study. METHODS: The semen analysis for volume, count, and motility
      was performed according to World Health Organization (2010) guidelines, using
      computer-assisted semen analysis. For the determination of spermatozoa
      morphology, a SpermBlue staining method was applied. Depending on their
      parameters, the sperm samples were categorized into normozoospermic,
      teratozoospermic, asthenoteratozoospermic, and oligoteratozoospermic. The seminal
      plasma content of iron, copper, zinc, and selenium was estimated by atomic
      absorption spectroscopy. The malondialdehyde and total glutathione levels were
      quantified spectrophotometrically. RESULTS: In the groups with poor sperm
      quality, the levels of Fe were higher, whereas those of Zn and Se were
      significantly lower than in the normozoospermic group. In all groups with poor
      sperm quality, increased levels of malondialdehyde and decreased glutathione
      levels were detected as evidence of oxidative stress occurrence. All these
      differences are most pronounced in the asthenoteratozoospermic group where values
      differ nearly twice as much compared to the normozoospermic group. The Fe
      concentration correlated positively with the malondialdehyde (r=0.666, p=0.018),
      whereas it showed a negative correlation with the level of total glutathione (r=
      0.689, p=0.013). The total glutathione level correlated positively with the sperm
      motility (r=0.589, p=0.044). CONCLUSION: The elevated levels of Fe and the
      reduced Se levels are associated with sperm damage. The changes in the
      concentrations of the trace elements in human seminal plasma may be related to
      sperm quality since they are involved in the maintenance of the pro
      /antioxidative balance in ejaculate.

PMID- 28443588
TI  - Solitary Fibrous Tumors of Chest: Another Look with the Oncologic Perspective.
AB  - Solitary fibrous tumors are mesenchymal lesions that arise at a variety of sites,
      most commonly the pleura. Most patients are asymptomatic at diagnosis, with
      lesions being detected incidentally. Nevertheless, some patients present due to
      symptoms from local tumor compression (eg. of the airways and pulmonary
      parenchyma). Furthermore, radiological methods are not always conclusive in
      making a diagnosis, and thus, pathological analysis is often required. In the
      past three decades, immunohistochemical techniques have provided a gold standard
      in solitary fibrous tumor diagnosis. The signature marker of solitary fibrous
      tumor is the presence of the NAB2-STAT6 fusion that can be reliably detected with
      a STAT6 antibody. While solitary fibrous tumors are most often benign, they can
      be malignant in 10-20% of the cases. Unfortunately, histological parameters are
      not always predictive of benign vs malignant solitary fibrous tumors. As solitary
      fibrous tumors are generally regarded as relatively chemoresistant tumors;
      treatment is often limited to localized treatment modalities. The optimal
      treatment of solitary fibrous tumors appears to be complete surgical resection
      for both primary and local recurrent disease. However, in cases of suboptimal
      resection, large disease burden, or advanced recurrence, a multidisciplinary
      approach may be preferable. Specifically, radiotherapy for inoperable local
      disease can provide palliation/shrinkage. Given their sometimes -unpredictable
      and often- protracted clinical course, long-term follow-up post-resection is
      recommended.

PMID- 28443589
TI  - The Influence of Inverted Growth Pattern on Recurrence for Patients with Non
      Invasive Low Grade Papillary Urothelial Carcinoma of Bladder.
AB  - AIMS: To evaluate the impact of a histologically inverted pattern on recurrence
      in patients with newly diagnosed non-invasive, low-grade papillary urothelial
      carcinoma of the urinary bladder. METHODS: A total of 81 patients with primary
      bladder non-invasive, low-grade papillary urothelial carcinoma diagnosed in a
      single tertiary-care centre who had at least 1-year follow-up after an initial
      resection were included. All slides from each case were reviewed to determine the
      growth pattern (exophytic versus endophytic, i.e. inverted) and other
      histological parameters. Clinical data were retrieved from hospital records.
      RESULTS: Disease recurrence occurred in 41 (50.6%) patients. Cases with an
      inverted pattern showed a lower recurrence rate than those with pure exophytic
      tumours (37.5% versus 52.1%), a longer time to first recurrence (mean 34 versus
      21.5 months) and fewer recurrence episodes (p=0.482, 0.564 and 0.051,
      respectively). All recurring inverted cases recurred only once during follow-up.
      No tumour with >80% inverted architecture recurred. CONCLUSION: Our results
      suggest that non-invasive, low-grade papillary urothelial carcinoma of the
      bladder tends to have a better outcome in terms of disease recurrence if it shows
      an inverted growth pattern. To indicate the presence and percentage of the
      inverted pattern in low-grade urothelial carcinomas in the pathology report might
      be considered as an adjunct to help long-term patient management.

PMID- 28443590
TI  - Effects of Apigenin on Experimental Ischemia/Reperfusion Injury in the Rat Ovary.
AB  - BACKGROUND: Apigenin is a plant-derived compound belonging to the flavone class,
      which possess antioxidant, free-radical-scavenging and anti-inflammatory
      properties. AIMS: To address the effects of apigenin on serum anti-mullerian
      hormone levels, tissue oxidative stress parameters and histopathological changes
      in ovarian ischemia/reperfusion injury. STUDY DESIGN: Animal experiment. METHODS:
      Twenty-eight female Wistar albino rats were randomly separated into four
      sections: Sham operation (group 1), ischemia/reperfusion plus saline (group 2),
      ischemia/reperfusion plus dimethyl sulfoxide (group 3) and ischemia/reperfusion
      plus apigenin (group 4). In all ischemia/reperfusion groups, a bilateral adnexal
      3-h period of ischemia was performed, followed by 3-h of reperfusion. A single
      dose of 15 mg/kg apigenin was given intraperitoneally 60 min before reperfusion
      in group 4. After 3-h of reperfusion, both ovaries were removed, and blood
      samples were collected. The main outcome measures were serum anti-mullerian
      hormone levels, ovarian tissue malondialdehyde, total nitric oxide, Cu/Zn
      superoxide dismutase, catalase and glutathione levels and histopathological
      damage scores. RESULTS: The ovarian tissue nitric oxide level was significantly
      lower, and the glutathione level was significantly higher in group 4 compared
      with groups 2 and 3. There was no significant difference in anti-mullerian
      hormone levels among the three ischemia/reperfusion groups. The histopathological
      damage score was lower in group 4 than in groups 2 and 3 (p>0.05). CONCLUSION:
      Administration of apigenin has no significant protective effect on ovarian
      reserve and tissue damage in ovarian ischemia/reperfusion injury.

PMID- 28443592
TI  - The Significance of A Neglected Romanian Book - "The Methods of the Clinical
      Laboratory", by Ioan Manta and Alexandru Ciplea.
AB  - "The Methods of Clinical Laboratory" was the first comprehensive Romanian book in
      the medical laboratory field, having utility in clinical practice. It was written
      by Prof. Ioan Manta (1900-1979) and Alexandru Ciplea (1912-1988), both from the
      Cluj Faculty of Medicine. The volume was published for the first time in 1944,
      during the refuge of this Faculty in Sibiu, and for the second time in 1947, in
      Cluj. Our aim is to make a brief analysis of its structure and to put into
      evidence the importance of this book for the Romanian laboratory medicine, some
      techniques (e.g. microscopic techniques) keeping their validity until today. The
      authors made over 800 detailed presentations about: laboratory sampling and
      preservation techniques, different types of tests and methods for qualitative and
      quantitative determinations, techniques to prepare various solutions,
      microbiological culture media, laboratory stains and reagents, as well as
      maneuvering of some laboratory equipments. For each method, Manta and Ciplea
      presented: the principle of working method, reagents required, the working
      technique, mode of calculation, the result and its interpretation. It also
      includes some laboratory apparatus descriptions, as well as their mode of
      working. With regard to the scientific value and to the practical utility of this
      book, it remains a very important milestone in the Romanian medical literature of
      the XX-th century.

PMID- 28443591
TI  - Clinical Findings of Pediatric HIV Infection in a Tertiary Center in Turkey.
AB  - BACKGROUND: Paediatric HIV infection is different from the adult type of disease
      in many ways, including transmission routes, clinical findings and treatment
      strategies. AIMS: To evaluate clinical data of paediatric patients with HIV
      disease. STUDY DESIGN: Retrospective cross-sectional study. METHODS: The charts
      of 22 paediatric patients diagnosed with HIV infection in our clinic during a 14
      year period through 2001-2015 were retrospectively analysed. Clinical data,
      laboratory findings, treatment modalities and outcomes were recorded. RESULTS:
      The mean age of diagnosis 61.9+/-49.2 months and the mean follow-up period was
      60.3+/-37.5 months. Seven patients (31.8%) were foreigners and the most common
      transmission route was vertical transmission (n=16, 72.7%). The most common
      presenting symptom and the sign were history of recurrent upper respiratory tract
      infections (n=8, 36.4%) and lymphadenopathy (n=12, 54.5%), respectively.
      Recurrent pneumonia (n=6, 27.3%), prolonged fever (n=5, 22.7%), recurrent otitis
      media (n=4, 18.2%), and gastroenteritis (n=4, 18.2%) were other clinical
      symptoms. Other than bacterial sinopulmonary infections, tuberculosis was the
      most frequent opportunistic infection (n=3, 13.6%). Mortality occurred in two
      patients (9.1%). CONCLUSION: Although mostly vertically transmitted, HIV
      infection may be diagnosed throughout the childhood. Frequently encountered signs
      and symptoms may be the reason for doctor admission. High clinical suspicion
      together with detailed anamnestic data and physical findings constitute the basis
      for pediatric HIV diagnosis.

PMID- 28443593
TI  - Value of Post-transfer Day-12 Beta Human Chorionic Gonadotropin Levels for
      Pregnancy Outcome Prediction of Intracytoplasmic Sperm Injection Cycles.
AB  - BACKGROUND: Several markers were studied previously in order to predict the
      pregnancy outcome of assisted reproductive techniques; however, serum beta human
      chorionic gonadotropin was found to be the most predictive marker. AIMS: To
      evaluate the value of serum beta human chorionic gonadotropin levels in
      discriminating biochemical and clinical pregnancies 12 days after embryo
      transfer, while determining the factors predicting ongoing pregnancy was
      established as the secondary aim. STUDY DESIGN: Retrospective cross-sectional
      study. METHODS: A total of 445 pregnant cycles were retrospectively analysed in
      2359 embryo transfer cycles. Patients were divided into two groups according to
      the outcome of pregnancy: biochemical and clinical. RESULTS: The cut-off value of
      beta human chorionic gonadotropin levels on day 12 in predicting clinical
      pregnancies was 86.8 IU/mL with 65.1% sensitivity and 74.7% specificity [CI: 0.76
      (0.71-0.81). Receiver operating characteristic curve analysis revealed different
      cut-off values for embryo transfer days (57 mIU/mL for day 3 embryo transfer CI:
      0.59-0.79 and 87 mIU/mL for day 5 embryo transfer, CI: 0.74-0.86). Subgroup
      analysis of clinical pregnancies revealed a significant difference between
      ongoing pregnancies and early fetal losses regarding duration of infertility
      (81.3+/-54.4 vs. 100.2+/-62.2 months), serum oestradiol on hCG day (2667.4+/
      1276.4 vs. 2094.6+/-1260.5 pg/mL), number of transferred embryos (1.9+/-0.8 vs.
      1.5+/-0.7) and the prevalence of diminished ovarian reserve as an indication
      (2.3% vs 12.2%). CONCLUSION: Beta human chorionic gonadotropin levels on day 12
      following embryo transfer provide an important parameter for the prediction of
      clinical pregnancy; however, other stimulation parameters are indicated in the
      prediction of ongoing pregnancies.

PMID- 28443594
TI  - Diastolic Electrocardiographic Parameters Predict Implantable Device Detected
      Asymptomatic Atrial Fibrillation.
AB  - BACKGROUND: Atrial fibrillation is the most common clinically significant
      arrhythmia. It is now established that atrial high-rate episodes are highly
      correlated with atrial fibrillation. AIMS: To investigate the relation between
      diastolic electrocardiographic parameters and subclinical atrial fibrillation
      detected by cardiac implantable electronic devices. STUDY DESIGN: Ccross
      sectional study. METHODS: A total of 203 patients who had a dual-chamber, rate
      modulated pacing pacemaker implanted due to sinus node dysfunction were
      prospectively enrolled in this study. Atrial high-rate episodes were defined as
      any lasting more than 5 min with an atrial rate of >=220 beats per minute during
      the previous year. Patient groups were categorized on the basis of pacemaker
      interrogation as the absence of atrial high-rate episodes [atrial high-rate
      episodes (-)] and the presence of atrial high-rate episodes [atrial high-rate
      episodes (+)]. Episodes related to atrial over sensing were excluded. Twelve-lead
      surface electrocardiography was independently analyzed by two experienced readers
      for the measurement of diastolic electrocardiography parameters. RESULTS: Among
      203 patients (mean age: 67.5+/-9.1, 60.1% male), 51 (25.1%) with atrial high-rate
      episodes were defined as group 1 and 152 (74.9%) without atrial high-rate
      episodes were defined as group 2. Both groups were similar in terms of
      demographic characteristics and cardiovascular risk factors. Tend-Q and Tend-P
      were significantly longer in group 2. PQ interval was statistically longer in
      group 1. Corrected QT interval was significantly longer in group 1. Diastolic
      electrocardiography index, heart rate and PQ and QT intervals were the only
      independent predictors of atrial high-rate episodes in patients with dual
      pacemakers in multivariate analysis. CONCLUSION: Abnormal diastolic
      electrocardiography parameters are powerful predisposing factors for the
      initiation of incident atrial fibrillation. Diastolic electrocardiography
      parameters and a novel diastolic index predict atrial high-rate episodes.
      Evaluating these parameters enables clinicians to identify patients who are at
      high risk and who may benefit from prophylactic treatment.

PMID- 28443595
TI  - Evaluation of the Diagnostic Role of Bedside Lung Ultrasonography in Patients
      with Suspected Pulmonary Embolism in the Emergency Department.
AB  - BACKGROUND: Despite the existence of detailed consensus guidelines, challenges
      remain regarding efficient, appropriate, and safe imaging methods for the
      diagnosis of suspected pulmonary embolism. AIMS: To investigate the role of the
      wedge sign, B-lines, and pleural effusion seen on bedside lung ultrasound in the
      diagnosis of pulmonary embolism. STUDY DESIGN: Diagnostic accuracy study.
      METHODS: During the first evaluation of patients with suspected pulmonary
      embolism, bedside lung ultrasound was performed, and the B-lines, wedge sign, and
      pleural effusion were investigated. Computed tomography angiography was used as a
      confirmatory test and was compared with the lung ultrasound findings. RESULTS:
      Pulmonary embolism was detected in 38 (38%) patients. In the comparison of
      bedside lung ultrasound results, statistically significant differences were found
      between the groups in terms of the B-lines and wedge sign (p=0.005 and p>0.001,
      respectively). There were no significant differences in terms of effusion
      (p=0.234). Comparison of these findings with computed tomography angiography of
      the chest showed weak negative correlations between the groups in terms of B
      lines (r=-0297) and a moderately positive correlation in terms of the wedge sign
      (r=0.523). The sensitivity, specificity, and positive and negative predictive
      values of lung ultrasound findings alone were low. In the logistic regression
      analysis, the wedge sign (p>0.01, OR=69.45, 95% CI=6.94-695.17) and B-line
      (p=0.033, OR=1.96, 95% CI=0.41-8.40) were found to be effective in the diagnosis
      of pulmonary embolism. CONCLUSION: Although the role of lung ultrasound has been
      increasing in the management of critically ill patients, its value is limited and
      cannot replace the gold standard tests in the diagnosis of pulmonary embolism.

PMID- 28443596
TI  - Lack of Association Between Toll-like Receptor 2 Polymorphisms (R753Q and A
      16934T) and Atopic Dermatitis in Children from Thrace Region of Turkey.
AB  - BACKGROUND: Atopic dermatitis is the most common chronic inflammatory skin
      disease. A complex interaction of both genetic and environmental factors is
      thought to contribute to the disease. AIMS: To evaluate whether single nucleotide
      polymorphisms in the TLR2 gene c.2258C>T (R753Q) (rs5743708) and TLR2 c.
      148+1614T>A (A-16934T) (rs4696480) (NM_0032643) are associated with atopic
      dermatitis in Turkish children. STUDY DESIGN: Case-control study. METHODS: The
      study was conducted on 70 Turkish children with atopic dermatitis aged 0.5-18
      years. The clinical severity of atopic dermatitis was evaluated by the severity
      scoring of atopic dermatitis index. Serum total IgE levels, specific IgE
      antibodies to inhalant and food allergens were measured in both atopic dermatitis
      patients and controls, skin prick tests were done on 70 children with atopic
      dermatitis. Genotyping for TLR2 (R753Q and A-16934T) single nucleotide
      polymorphisms was performed in both atopic dermatitis patients and controls.
      RESULTS: Cytosine-cytosine and cytosin-thymine genotype frequencies of the TLR2
      R753Q single nucleotide polymorphism in the atopic dermatitis group were
      determined as being 98.6% and 1.4%, cytosine allele frequency for TLR2 R753Q
      single nucleotide polymorphism was determined as 99.29% and the thymine allele
      frequency was 0.71%, thymine-thymine, thymine-adenine, and adenine-adenine
      genotype frequencies of the TLR2 A-16934T single nucleotide polymorphism were
      24.3%, 44.3%, and 31.4%. The thymine allele frequency for the TLR2 A-16934T
      single nucleotide polymorphism in the atopic dermatitis group was 46.43%, and the
      adenine allele frequency was 53.57%, respectively. There was not statistically
      significant difference between the groups for all investigated polymorphisms
      (p>0.05). For all single nucleotide polymorphisms studied, allelic distribution
      was analogous among atopic dermatitis patients and controls, and no significant
      statistical difference was observed. No homozygous carriers of the TLR2 R753Q
      single nucleotide polymorphism were found in the atopic dermatitis and control
      groups. CONCLUSION: The TLR2 (R753Q and A-16934T) single nucleotide polymorphisms
      are not associated with atopic dermatitis in a group of Turkish patients.

PMID- 28443597
TI  - A Different SLC2A1 Gene Mutation in Glut 1 Deficiency Syndrome: c.734A>C.
AB  - BACKGROUND: Glucose transporter type 1 deficiency syndrome is the result of
      impaired glucose transport into the brain. Patients with glucose transporter type
      1 syndrome may present with infantile seizures, developmental delay, acquired
      microcephaly, spasticity and ataxia. CASE REPORT: Here, we report a rare case of
      glucose transporter type 1 deficiency syndrome caused by a different pathogenic
      variant in a 10-day-old neonate who presented with intractable seizures and
      respiratory arrest. CONCLUSION: This new pathogenic variant can be seen in
      glucose transporter type 1 deficiency syndrome.

PMID- 28443598
TI  - Evaluation of Inferior Turbinate Stroma with Ultrasound Elastography in Allergic
      Rhinitis Patients.
AB  - BACKGROUND: Diagnosis of allergic rhinitis is primarily based on history,
      physical examination and allergy testing. A technique that noninvasively
      evaluates the soft tissue changes in the nasal mucosa of allergic rhinitis
      patients has not been defined. AIMS: To assess nasal mucosal changes and measure
      the submucosal fibrosis in allergic rhinitis patients with sonoelastography.
      STUDY DESIGN: Case control study. METHODS: Eighty-eight turbinates of 44 patients
      were included in the study. There were 23 prick test positive allergic rhinitis
      patients. The control group constituted 21 patients. The rhinitis quality of life
      questionnaire and the visual analogue scale were applied to the allergic rhinitis
      patients. A higher visual analogue scale score indicated more severe allergic
      rhinitis symptoms. Sonoelastographic measurements were made from the lateral
      nasal wall. The propagation speed of sound waves was recorded in m/s. The
      presence of asthma and the type of allergic rhinitis (seasonal or perennial) was
      noted. RESULTS: Ten patients had seasonal allergic rhinitis and thirteen patients
      had perennial allergic rhinitis. Six patients (26.1%) had accompanying asthma
      along with allergic rhinitis. The median visual analogue scale score was 7 (3-9)
      in allergic rhinitis patients. The median symptom duration was 7 (1-24) months.
      The median quality of life questionnaire score was 3.39 (1.68-5.43) points. The
      median sonoelastography scores of allergic rhinitis patients and healthy subjects
      were 2.38 m/s (0.9-4.47) and 2.42 m/s (1.62-3.50), respectively.
      Sonoelastographic measurements of seasonal and perennial allergic rhinitis
      patients did not differ significantly (p<0.05). The presence of asthma did not
      have a significant impact on the elastography measurements (<0.05). However,
      regression analysis revealed a significant inverse correlation (coefficients:
      B=0.005, standard error=0.097, beta 0=0.008) between the visual analogue scale
      and sonoelastography scores (p>0.05). CONCLUSION: Sonoelastography was not
      suitable as a diagnostic tool in allergic rhinitis. Reduced sonoelastography
      scores were measured in more symptomatic patients. Higher visual analogue scale
      scores could be an indicator of disease severity.

PMID- 28443599
TI  - A Pott's Puffy Tumor Associated with Epidural - Cutaneous Fistula and Epidural
      Abscess: Case Report.
AB  - BACKGROUND: Pott's puffy tumour is characterized by a fluctuate swelling of the
      frontal region as a result of osteomyelitis of the frontal bone. This
      inflammatory lesion may propagate endocranially, resulting in acute meningitis,
      epidural abscess, subdural empyema, cavernous sinus trombophlebitis, cerebritis,
      and frontal lobe abscess of the brain. CASE REPORT: We present an unusual case of
      a 33-year-old man suffering from Pott's puffy tumour whose condition was further
      complicated by a draining epidural-cutaneous fistula and an epidural abscess. We
      confirmed the diagnosis by contrast-enhanced computed tomography scanning and
      magnetic resonance imaging of the head. After intense antibiotic treatment, we
      performed a combined endoscopic and external surgical approach with drainage of
      abscesses, evacuation of pus and bone sequestrate and excision of fistulous
      lesion. The treatment was prolonged with four weeks' antibiotic administration.
      CONCLUSION: Subperiosteal abscess of the frontal bone is an extremely rare
      complication of frontal sinusitis. This lesion may propagate endocranially,
      resulting in dangerous intracranial inflammatory lesions. Early diagnosis,
      medication and surgical therapy are very important in reducing morbidity and
      mortality.

PMID- 28443600
TI  - Retroauricular Approach for Targeted Cochlear Therapy Experiments in Wistar
      Albino Rats.
AB  - BACKGROUND: As the idea of stem cell technology in the treatment of sensorial
      hearing loss has emerged over the past decades, the need for in vivo models for
      related experiments has become explicit. One of the most common experimental
      models for inner ear stem cell delivery experiments is the Wistar albino rat.
      AIMS: To investigate the surgical anatomy of the temporal bone of the Wistar
      albino rat with respect to the dissection steps, operative techniques and
      potential pitfalls of surgery. STUDY DESIGN: Animal experimentation. METHODS:
      Adult Wistar albino rats were operated on via the retroauricular approach under
      an operation microscope. The anatomy of the temporal bone, the surgical route to
      the temporal bulla and the inner ear were investigated. Technical details of
      surgical steps, complications and potential pitfalls during the surgery were
      noted. RESULTS: The study group consisted of 40 adult Wistar albino rats. The
      mean times to reach the bulla and to achieve cochleostomy were 4.3 (2-13 min) and
      7.5 min (3.5-22 min), respectively. The mean width of the facial nerve was 0.84
      mm (0.42-1.25 mm). The stapedial artery lay nearly perpendicular to the course of
      the facial nerve (88-93  degrees C). There were three major complications: two
      large cochleostomies and one massive bleed from the stapedial artery. CONCLUSION:
      The facial nerve was the key anatomical landmark in locating the bulla. By
      retrograde tracing of the facial nerve, it was possible to find the bulla ventral
      (inferior) to the main trunk. The facial nerve trunk was the upper limit when
      drilling the bulla. By dissecting the main trunk of the facial nerve and
      retracting cranially, a large drilling space could be achieved. Our results
      suggest that the retroauricular approach is an effective, feasible route for
      inner ear drug delivery experiments in Wistar albino rats.

PMID- 28443601
TI  - Self-assembly of defect-rich graphene oxide nanosheets with Na2Ti3O7 nanowires
      and their superior absorptive capacity to toxic dyes.
AB  - Graphene sheets, a flexible 2D material with excellent absorptive capacity, have
      great potential as absorbing materials. However, this material has always
      suffered from irreversible aggregation and thus loses the abundant active sites
      and large surface area. In this paper, large-scale graphene oxide (GO) sheets
      were cut and reduced to tiny reduced graphene oxide (RGO) sheets by a cell-break
      sonicator, for producing numerous defects, which are the center of chemisorption.
      Furthermore, sodium titanate nanowires functioned as a framework to help to
      disperse the tiny RGO sheets uniformly. And, in turn, the flexible tiny RGO
      sheets glued robust nanowires into a free-standing membrane. This novel composite
      membrane exhibited an ultra-high decoloration efficiency of 99.8% of rhodamine B
      in a continuous flow mode, and an outstanding absorptive capability of 1.30 * 10
      2 mol g-1 correlated to RGO content in batch reaction, which is about two orders
      of magnitude higher than other reported graphene-based absorbents. In addition,
      an efficient and feasible method without any heat treatment for regenerating the
      membrane is illustrated, and the recycled membrane retains superior decoloration
      efficiency. The excellent absorptive performance indicates the framework-based
      disperse strategy has great potential for the construction and application of
      defect-rich graphene.

PMID- 28443602
TI  - Fundamental limits on the electron mobility of beta-Ga2O3.
AB  - We perform first-principles calculations to investigate the electronic and
      vibrational spectra and the electron mobility of beta-Ga2O3. We calculate the
      electron-phonon scattering rate of the polar optical phonon modes using the Vogl
      model in conjunction with Fermi's golden rule; this enables us to fully take the
      anisotropic phonon spectra of the monoclinic lattice of beta-Ga2O3 into account.
      We also examine the scattering rate due to ionized impurities or defects using a
      Yukawa-potential-based model. We consider scattering due to donor impurities, as
      well as the possibility of compensation by acceptors such as Ga vacancies. We
      then calculate the room-temperature mobility of beta-Ga2O3 using the Boltzmann
      transport equation within the relaxation time approximation, for carrier
      densities in the range from 1017 to 1020 cm-3. We find that the electron-phonon
      interaction dominates the mobility for carrier densities of up to 1019 cm-3. We
      also find that the intrinsic anisotropy in the mobility is small; experimental
      findings of large anisotropy must therefore be attributed to other factors. We
      attribute the experimentally observed reduction of the mobility with increasing
      carrier density to increasing levels of compensation, which significantly affect
      the mobility.

PMID- 28443603
TI  - Hard x-ray photoemission study of Yb1-x Zr x B12: the effects of electron doping
      on the Kondo insulator YbB12.
AB  - We have carried out hard x-ray photoemission spectroscopy (HAXPES) of Yb1-x Zr x
      B12 ([Formula: see text]) to study the effects of electron doping on the Kondo
      insulator YbB12. The Yb valences of Yb1-x Zr x B12 at 300 K estimated from the Yb
      3d HAXPES spectra decreased after substituting Yb with Zr from 2.93 for YbB12 to
      2.83 for Yb0.125Zr0.875B12. A temperature dependent valence decrease was found
      upon cooling for all doping concentrations. We found peak shifts of the B 1s and
      Zr 3d5/2, and Yb3+ 4f spectra toward the deeper binding-energy with increasing Zr
      concentration, which indicates a shift of the Fermi level to the higher energy
      and that of the Yb 4f hole level close to the Fermi level, respectively, due to
      electron doping. These results qualitatively show the enhanced hybridization
      between the Yb 4f and conduction-band states with Zr substitution, consistent
      with magnetic susceptibility measurements.

PMID- 28443604
TI  - Edge-functionalization of armchair graphene nanoribbons with pentagonal-hexagonal
      edge structures.
AB  - Using density functional theory calculations, we have studied the edge
      functionalization of armchair graphene nanoribbons (AGNRs) with pentagonal
      hexagonal edge structures. While the AGNRs with pentagonal-hexagonal edge
      structures (labeled (5,6)-AGNRs) are metallic, the edge-functionalized (5,6)
      AGNRs with substitutional atoms opens a band gap. We find that the band
      structures of edge-functionalized (5,6)-N-AGNRs by substitution resemble those of
      defect-free (N-1)-AGNR at the Gamma point, whereas those at the X point show the
      original ones of the defect-free N-AGNR. The overall electronic structures of
      edge-functionalized (5,6)-AGNRs depend on the number of electrons, supplied by
      substitutional atoms, at the edges of functionalized (5,6)-AGNRs.

PMID- 28443606
TI  - Genotype-outcome correlations in pediatric AML: the impact of a monosomal
      karyotype in trial AML-BFM 2004.
AB  - We conducted a cytogenetic analysis of 642 children with de novo acute myeloid
      leukemia (AML) treated on the AML-Berlin-Frankfurt-Munster (BFM) 04 protocol to
      determine the prognostic value of specific chromosomal aberrations including
      monosomal (MK+), complex (CK+) and hypodiploid (HK+) karyotypes, individually and
      in combination. Multivariate regression analysis identified in particular MK+
      (n=22) as a new independent risk factor for poor event-free survival (EFS 23+/-9%
      vs 53+/-2% for all other patients, P=0.0003), even after exclusion of four
      patients with monosomy 7 (EFS 28+/-11%, P=0.0081). CK+ patients without MK had a
      better prognosis (n=47, EFS 47+/-8%, P=0.46) than those with MK+ (n=12, EFS 25+/
      13%, P=0.024). HK+ (n=37, EFS 44+/-8% for total cohort, P=0.3) influenced outcome
      only when t(8;21) patients were excluded (remaining n=16, EFS 9+/-8%, P<0.0001).
      An extremely poor outcome was observed for MK+/HK+ patients (n=10, EFS 10+/-10%,
      P<0.0001). Finally, isolated trisomy 8 was also associated with low EFS (n=16,
      EFS 25+/-11%, P=0.0091). In conclusion, monosomal karyotype is a strong and
      independent predictor for high-risk pediatric AML. In addition, isolated trisomy
      8 and hypodiploidy without t(8;21) coincide with dismal outcome. These results
      have important implications for risk stratification and should be further
      validated in independent pediatric cohorts.

PMID- 28443607
TI  - Novel approaches for the promotion of physical activity and exercise for
      prevention and management of type 2 diabetes.
AB  - Despite increased evidence for the importance of lifestyle modification, physical
      activity and diet in diabetes prevention and management, habitual physical
      activity levels have declined in recent decades in China and India. Further,
      other risk factors for type 2 diabetes, including overweight, obesity and
      physical inactivity, have also worsened. Here we present evidence for the
      importance of physical activity and exercise in the amelioration of type 2
      diabetes and propose a novel approach to address the challenge of improving
      lifestyle behaviors in China and India-Movement is Medicine and a P4 (predictive,
      preventive, personalized and participatory) approach.

PMID- 28443608
TI  - Dynamic behaviour of interphases and its implication on high-energy-density
      cathode materials in lithium-ion batteries.
AB  - Undesired electrode-electrolyte interactions prevent the use of many high-energy
      density cathode materials in practical lithium-ion batteries. Efforts to address
      their limited service life have predominantly focused on the active electrode
      materials and electrolytes. Here an advanced three-dimensional chemical and
      imaging analysis on a model material, the nickel-rich layered lithium transition
      metal oxide, reveals the dynamic behaviour of cathode interphases driven by
      conductive carbon additives (carbon black) in a common nonaqueous electrolyte.
      Region-of-interest sensitive secondary-ion mass spectrometry shows that a cathode
      electrolyte interphase, initially formed on carbon black with no electrochemical
      bias applied, readily passivates the cathode particles through mutual exchange of
      surface species. By tuning the interphase thickness, we demonstrate its
      robustness in suppressing the deterioration of the electrode/electrolyte
      interface during high-voltage cell operation. Our results provide insights on the
      formation and evolution of cathode interphases, facilitating development of in
      situ surface protection on high-energy-density cathode materials in lithium-based
      batteries.

PMID- 28443610
TI  - Ordered micro/macro porous K-OMS-2/SiO2 nanocatalysts: Facile synthesis, low cost
      and high catalytic activity for diesel soot combustion.
AB  - A series of novel oxide catalysts, which contain three-dimensionally ordered
      macroporous (3DOM) and microporous structure, were firstly designed and
      successfully synthesized by simple method. In the as-prepared catalysts, 3DOM
      SiO2 is used as support and microporous K-OMS-2 oxide nanoparticles are supported
      on the wall of SiO2. 3DOM K-OMS-2/SiO2 oxide catalysts were firstly used in soot
      particle oxidation reaction and they show very high catalytic activities. The
      high activities of K-OMS-2/SiO2 oxide catalysts can be assigned to three possible
      reasons: macroporous effect of 3DOM structure for improving contact between soot
      and catalyst, microporous effect of K-OMS-2 for adsorption of small gas molecules
      and interaction of K and Mn for activation of gas molecules. The catalytic
      activities of catalysts are comparable to or even higher than noble metal
      catalyst in the medium and high temperature range. For example, the T50 of K-OMS
      2/SiO2-50, 328  degrees C, is much lower than those of Pt/Al2O3 and 3DOM
      Au/LaFeO3, 464 and 356  degrees C,respectively. Moreover, catalysts exhibited
      high catalytic stability. It is attributed to that the K+ ions are introduced
      into the microporous structure of OMS-2 and stabilized in the catalytic reaction.
      Meanwhile, the K+ ions play an important role in templating and stabilizing the
      tunneled framework of OMS-2.

PMID- 28443609
TI  - The HIV-1 viral synapse signals human foreskin keratinocytes to secrete thymic
      stromal lymphopoietin facilitating HIV-1 foreskin entry.
AB  - The complexity of signal transduction resulting from the contact of human
      immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has
      hampered our comprehension of HIV-1 mucosal entry. Such process is driven
      efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains
      poorly infectious. Using CD4+ T-cells expressing only HIV-1 envelope inoculated
      on human adult foreskin tissues, we designed methodologies to identify the
      signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent
      viral synapse formation. We find that the viral synapse activates the MyD88
      independent TLR-4-nuclear factor (NfkappaB) signaling pathway in keratinocytes
      and the subsequent secretion of cytokines including thymic stromal lymphopoietin
      (TSLP), a cytokine linking innate and T-helper type 2-adaptive immune responses.
      Moreover, the viral synapse upregulates the non-coding microRNA miR-375, known to
      control TSLP, and transfection of keratinocytes with anti-miR-375 blocks
      significantly TSLP secretion. Thus, the secretion of TSLP by keratinocytes is
      induced by the viral synapse in a miR-375 controlled manner. At the tissue level,
      these signals translate into the epidermal redistribution of Langerhans cells and
      formation of conjugates with T-cells, recapitulating the initial events observed
      in human foreskin infection by HIV-1. These results open new possibilities for
      designing strategies to block mucosal HIV-1 transmission, the major pathway by
      which HIV-1 spreads worldwide.

PMID- 28443611
TI  - Corrigendum: The driving force of prophages and CRISPR-Cas system in the
      evolution of Cronobacter sakazakii.

PMID- 28443612
TI  - Dynamically unpolarized single-photon source in diamond with intrinsic
      randomness.
AB  - Polarization is one of the fundamental properties of light, providing numerous
      applications in science and technology. While 'dynamically unpolarized' single
      photon sources are demanded for various quantum applications, such sources have
      never been explored. Here we demonstrate dynamically unpolarized single-photon
      emission from a single [111]-oriented nitrogen- vacancy centre in diamond, in
      which the single-photon stream is unpolarized, exhibiting intrinsic randomness
      with vanishing polarization correlation between time adjacent photons. These
      properties not only allow true random number generation, but may also enable
      fundamental tests in quantum physics.

PMID- 28443613
TI  - Corrigendum: Intronless WNT10B-short variant underlies new recurrent allele
      specific rearrangement in acute myeloid leukaemia.

PMID- 28443614
TI  - Cocaine Cue-Induced Dopamine Release in Recreational Cocaine Users.
AB  - It has been proposed that the acquisition of drug seeking is related to the
      development of conditioned dopamine responses in the ventral striatum. As drug
      use continues and becomes habit-like, conditioned responses have been shown to
      shift to the dorsal striatum. Here, using the PET [11C]raclopride method and
      highly personalized cocaine cues, we report the first evidence in humans of the
      dorsal dopamine response prior to the onset of addiction.

PMID- 28443615
TI  - The plant cell-wall enzyme AtXTH3 catalyses covalent cross-linking between
      cellulose and cello-oligosaccharide.
AB  - Cellulose is an economically important material, but routes of its industrial
      processing have not been fully explored. The plant cell wall - the major source
      of cellulose - harbours enzymes of the xyloglucan endotransglucosylase/hydrolase
      (XTH) family. This class of enzymes is unique in that it is capable of elongating
      polysaccharide chains without the requirement for activated nucleotide sugars
      (e.g., UDP-glucose) and in seamlessly splitting and reconnecting chains of
      xyloglucan, a naturally occurring soluble analogue of cellulose. Here, we show
      that a recombinant version of AtXTH3, a thus far uncharacterized member of the
      Arabidopsis XTH family, catalysed the transglycosylation between cellulose and
      cello-oligosaccharide, between cellulose and xyloglucan-oligosaccharide, and
      between xyloglucan and xyloglucan-oligosaccharide, with the highest reaction rate
      observed for the latter reaction. In addition, this enzyme formed cellulose-like
      insoluble material from a soluble cello-oligosaccharide in the absence of
      additional substrates. This newly found activity (designated "cellulose
      endotransglucosylase," or CET) can potentially be involved in the formation of
      covalent linkages between cellulose microfibrils in the plant cell wall. It can
      also comprise a new route of industrial cellulose functionalization.

PMID- 28443616
TI  - Effects of Extended Cannabis Abstinence on Cognitive Outcomes in Cannabis
      Dependent Patients with Schizophrenia vs Non-Psychiatric Controls.
AB  - Cross-sectional studies of the effects of cannabis on cognition in schizophrenia
      have produced mixed results. Heavy and persistent cannabis use in schizophrenia
      is a common clinical problem, and effects of controlled abstinence from cannabis
      in these patients have not been carefully evaluated. The present study sought to
      determine the effects of cannabis abstinence on cognition in patients with
      schizophrenia and co-occurring cannabis dependence. We utilized a 28-day cannabis
      abstinence paradigm to investigate the state-dependent effects of cannabis on
      select cognitive outcomes in cannabis-dependent patients with schizophrenia and
      non-psychiatric controls. Nineteen patients and 20 non-psychiatric male cannabis
      dependent participants underwent 28 days of cannabis abstinence. Cognition was
      assessed on day 0, 14, and 28 using a comprehensive neuropsychological battery.
      Clinical symptoms were assessed weekly. Abstinence was facilitated by contingency
      reinforcement confirmed by twice weekly urinalysis. Forty-two percent of patients
      and 55% of controls achieved end-point abstinence (p=0.53), which was
      biochemically-verified (day 28 urinary THC-COOH <20 ng/ml). In this preliminary
      study, schizophrenia-abstainers demonstrated improvements in Hopkins Verbal
      Learning Test-Revised (HVLT-R) performance over time [F(2,14)=4.73, p<0.03]
      (d=1.07). Lesser improvements on HVLT-R were observed in non-psychiatric control
      abstainers (d=0.66), and with abstinence on other cognitive test measures, in
      both patients and controls. Verbal memory and learning may improve in
      schizophrenia and control subjects with cannabis abstinence, but larger more
      definitive studies are needed. Our findings underscore the importance of
      developing effective interventions for cannabis use disorders in schizophrenia.

PMID- 28443618
TI  - Engineering of orbital angular momentum supermodes in coupled optical waveguides.
AB  - In this work we demonstrate the existence of orbital angular momentum (OAM)
      bright and dark supermodes in a three-evanescently coupled cylindrical waveguides
      system. Bright and dark supermodes are characterized by their coupling and
      decoupling from one of the waveguides, respectively. In addition, we demonstrate
      that complex couplings between modes of different waveguides appear naturally due
      to the characteristic spiral phase-front of OAM modes in two-dimensional
      configurations where the waveguides are arranged forming a triangle. Finally, by
      adding dissipation to the waveguide uncoupled to the dark supermode, we are able
      to filter this supermode out, allowing for the design of OAM mode cloners and
      inverters.

PMID- 28443617
TI  - The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future.
AB  - Plant-based psychedelics, such as psilocybin, have an ancient history of
      medicinal use. After the first English language report on LSD in 1950,
      psychedelics enjoyed a short-lived relationship with psychology and psychiatry.
      Used most notably as aids to psychotherapy for the treatment of mood disorders
      and alcohol dependence, drugs such as LSD showed initial therapeutic promise
      before prohibitive legislature in the mid-1960s effectively ended all major
      psychedelic research programs. Since the early 1990s, there has been a steady
      revival of human psychedelic research: last year saw reports on the first modern
      brain imaging study with LSD and three separate clinical trials of psilocybin for
      depressive symptoms. In this circumspective piece, RLC-H and GMG share their
      opinions on the promises and pitfalls of renewed psychedelic research, with a
      focus on the development of psilocybin as a treatment for depression.

PMID- 28443619
TI  - Programming mRNA decay to modulate synthetic circuit resource allocation.
AB  - Synthetic circuits embedded in host cells compete with cellular processes for
      limited intracellular resources. Here we show how funnelling of cellular
      resources, after global transcriptome degradation by the sequence-dependent
      endoribonuclease MazF, to a synthetic circuit can increase production. Target
      genes are protected from MazF activity by recoding the gene sequence to eliminate
      recognition sites, while preserving the amino acid sequence. The expression of a
      protected fluorescent reporter and flux of a high-value metabolite are
      significantly enhanced using this genome-scale control strategy. Proteomics
      measurements discover a host factor in need of protection to improve resource
      redistribution activity. A computational model demonstrates that the MazF mRNA
      decay feedback loop enables proportional control of MazF in an optimal operating
      regime. Transcriptional profiling of MazF-induced cells elucidates the dynamic
      shifts in transcript abundance and discovers regulatory design elements.
      Altogether, our results suggest that manipulation of cellular resource allocation
      is a key control parameter for synthetic circuit design.

PMID- 28443620
TI  - Reply to A Mackie.

PMID- 28443621
TI  - UK National Screening Committee Criteria: clarification of two misunderstandings.

PMID- 28443622
TI  - The RUDY study: using digital technologies to enable a research partnership.
AB  - Patients have extensive experience of their disease that can enhance the design
      and execution of research leading to significant innovations and efficiencies in
      the research process. The research community on the whole have been slow to adopt
      practices that enable patients to become active partners in research. Digital
      technologies are providing the means to do this more easily and so are
      increasingly being used to interact with patients and involve them in the design
      and execution of research. The RUDY (Rare UK Diseases of bone, joints and blood
      vessels) study's pioneering approach applies a custom-developed electronic
      platform where patients can contribute information over time about their disease
      experience, lifestyle and clinical history. This is combined with a state-of-the
      art Dynamic Consent model and a commitment to patient-driven research, to further
      our understanding of rare diseases. This paper describes the RUDY study and the
      benefits that have been gained from adopting this partnership approach to
      research.

PMID- 28443623
TI  - Novel SLC25A32 mutation in a patient with a severe neuromuscular phenotype.
AB  - In a 51-year-old patient of consanguineous parents with a severe neuromuscular
      phenotype of early-onset ataxia, myoclonia, dysarthria, muscle weakness and
      exercise intolerance, exome sequencing revealed a novel homozygous variant (c.
      264_31delinsCTCACAAATGCTCA) in the mitochondrial FAD-transporter gene SLC25A32.
      Flavin adenine dinucleotide (FAD) is an essential co-factor for many
      mitochondrial enzymes and impaired mitochondrial FAD-transport was supported by a
      reduced oxidative phosphorylation complex II activity in the patient's muscle,
      decreased ATP production in fibroblasts, and a deficiency of mitochondrial FAD
      dependent enzymes. Clinically, the patient showed improvement upon riboflavin
      treatment, which is a precursor of FAD. Our results confirm the recently reported
      case of SLC25A32 as a cause of riboflavin-responsive disease. Our patient showed
      a more severe clinical phenotype compared with the reported patient,
      corresponding with the (most likely) complete absence of the SLC25A32-encoding
      MFT (Mitochondrial Folate Transporter) protein.

PMID- 28443624
TI  - Fundamental limits of repeaterless quantum communications.
AB  - Quantum communications promises reliable transmission of quantum information,
      efficient distribution of entanglement and generation of completely secure keys.
      For all these tasks, we need to determine the optimal point-to-point rates that
      are achievable by two remote parties at the ends of a quantum channel, without
      restrictions on their local operations and classical communication, which can be
      unlimited and two-way. These two-way assisted capacities represent the ultimate
      rates that are reachable without quantum repeaters. Here, by constructing an
      upper bound based on the relative entropy of entanglement and devising a
      dimension-independent technique dubbed 'teleportation stretching', we establish
      these capacities for many fundamental channels, namely bosonic lossy channels,
      quantum-limited amplifiers, dephasing and erasure channels in arbitrary
      dimension. In particular, we exactly determine the fundamental rate-loss tradeoff
      affecting any protocol of quantum key distribution. Our findings set the limits
      of point-to-point quantum communications and provide precise and general
      benchmarks for quantum repeaters.

PMID- 28443626
TI  - Nanodiamond-enhanced MRI via in situ hyperpolarization.
AB  - Nanodiamonds are of interest as nontoxic substrates for targeted drug delivery
      and as highly biostable fluorescent markers for cellular tracking. Beyond optical
      techniques, however, options for noninvasive imaging of nanodiamonds in vivo are
      severely limited. Here, we demonstrate that the Overhauser effect, a proton
      electron polarization transfer technique, can enable high-contrast magnetic
      resonance imaging (MRI) of nanodiamonds in water at room temperature and ultra
      low magnetic field. The technique transfers spin polarization from paramagnetic
      impurities at nanodiamond surfaces to 1H spins in the surrounding water solution,
      creating MRI contrast on-demand. We examine the conditions required for maximum
      enhancement as well as the ultimate sensitivity of the technique. The ability to
      perform continuous in situ hyperpolarization via the Overhauser mechanism, in
      combination with the excellent in vivo stability of nanodiamond, raises the
      possibility of performing noninvasive in vivo tracking of nanodiamond over
      indefinitely long periods of time.

PMID- 28443627
TI  - Multifunctionality of silver closo-boranes.
AB  - Silver compounds share a rich history in technical applications including
      photography, catalysis, photocatalysis, cloud seeding and as antimicrobial
      agents. Here we present a class of silver compounds (Ag2B10H10 and Ag2B12H12)
      that are semiconductors with a bandgap at 2.3 eV in the green visible light
      spectrum. The silver boranes have extremely high ion conductivity and dynamic
      anion facilitated Ag+ migration is suggested based on the structural model. The
      ion conductivity is enhanced more than two orders of magnitude at room
      temperature (up to 3.2 mS cm-1) by substitution with AgI to form new compounds.
      Furthermore, the closo-boranes show extremely fast silver nano-filament growth
      when excited by electrons during transmission electron microscope investigations.
      Ag nano-filaments can also be reabsorbed back into Ag2B12H12. These interesting
      properties demonstrate the multifunctionality of silver closo-boranes and open up
      avenues in a wide range of fields including photocatalysis, solid state ionics
      and nano-wire production.

PMID- 28443628
TI  - Intestinal microbiota link lymphopenia to murine autoimmunity via PD-1+CXCR5-/dim
      B-helper T cell induction.
AB  - T cell lymphopenia results in peripheral homeostatic expansion to maintain the T
      cell immune system, which is termed lymphopenia-induced proliferation (LIP). LIP
      is a potential risk for expanding autoreactive clones to become pathogenic in
      human and murine autoimmune diseases. However, the ontogeny of T cells that
      induce autoantibody production by autoreactive B cells in LIP remains unclear.
      Transfer of CD4+CD25- conventional T (Tc) cells into T-cell-deficient athymic
      nude mice has been previously reported as a LIP-induced autoimmune model which
      develops organ-specific autoimmune diseases and systemic antinuclear antibodies
      (ANAs). We show here that via LIP in this model, Tc cells proliferated and
      differentiated into PD-1+CXCR5-/dim B-helper T cells, which promoted splenic
      germinal center (GC) formation, provided help for autoantibody-producing B cells,
      and had distinctive features of follicular helper T (Tfh) cells except that they
      do not express high CXCR5. Intestinal microbiota were essential for their
      generation, since depletion of them in recipient mice by antibiotics resulted in
      a reduction of LIP-induced PD-1+CXCR5-/dim B-helper T cells and an amelioration
      of autoimmune responses. Our findings will contribute to the elucidation of the
      mechanism of lymphopenia-induced autoimmunity and autoantibody production, and
      will pave the way for microbiota-targeted novel therapeutic approaches to
      systemic autoimmune diseases.

PMID- 28443630
TI  - Accelerating recovery from jet lag: prediction from a multi-oscillator model and
      its experimental confirmation in model animals.
AB  - The endogenous circadian clock drives oscillations that are completely
      synchronized with the environmental day-night rhythms with a period of
      approximately 24 hours. Temporal misalignment between one's internal circadian
      clock and the external solar time often occurs in shift workers and long-distance
      travelers; such misalignments are accompanied by sleep disturbances and
      gastrointestinal distress. Repeated exposure to jet lag and rotating shift work
      increases the risk of lifestyle-related diseases, such as cardiovascular
      complaints and metabolic insufficiencies. However, the mechanism behind the
      disruption of one's internal clock is not well understood. In this paper, we
      therefore present a new theoretical concept called "jet lag separatrix" to
      understand circadian clock disruption and slow recovery from jet lag based on the
      mathematical model describing the hierarchical structure of the circadian clock.
      To demonstrate the utility of our theoretical study, we applied it to predict
      that re-entrainment via a two-step jet lag in which a four-hour shift of the
      light-dark cycle is given in the span of two successive days requires fewer days
      than when given as a single eight-hour shift. We experimentally verified the
      feasibility of our theory in C57BL/6 strain mice, with results indicating that
      this pre-exposure of jet lag is indeed beneficial.

PMID- 28443629
TI  - Differences in peripheral sensory input to the olfactory bulb between male and
      female mice.
AB  - Female mammals generally have a superior sense of smell than males, but the
      biological basis of this difference is unknown. Here, we demonstrate sexually
      dimorphic neural coding of odorants by olfactory sensory neurons (OSNs), primary
      sensory neurons that physically contact odor molecules in the nose and provide
      the initial sensory input to the brain's olfactory bulb. We performed in vivo
      optical neurophysiology to visualize odorant-evoked OSN synaptic output into
      olfactory bub glomeruli in unmanipulated (gonad-intact) adult mice from both
      sexes, and found that in females odorant presentation evoked more rapid OSN
      signaling over a broader range of OSNs than in males. These spatiotemporal
      differences enhanced the contrast between the neural representations of
      chemically related odorants in females compared to males during stimulus
      presentation. Removing circulating sex hormones makes these signals slower and
      less discriminable in females, while in males they become faster and more
      discriminable, suggesting opposite roles for gonadal hormones in influencing male
      and female olfactory function. These results demonstrate that the famous sex
      difference in olfactory abilities likely originates in the primary sensory
      neurons, and suggest that hormonal modulation of the peripheral olfactory system
      could underlie differences in how males and females experience the olfactory
      world.

PMID- 28443633
TI  - Corrigendum: Characterization of a P1-like bacteriophage carrying CTX-M-27 in
      Salmonella spp. resistant to third generation cephalosporins isolated from pork
      in China.

PMID- 28443632
TI  - Erratum: Loss of miR-542-3p enhances IGFBP-1 expression in decidualizing human
      endometrial stromal cells.

PMID- 28443634
TI  - A unifying mathematical framework for experimental TCR-pMHC kinetic constants.
AB  - Receptor binding and triggering are central in Immunology as T cells activated
      through their T cell receptors (TCR) by protein antigens orchestrate immune
      responses. In order to understand receptor-ligand interactions, many groups
      working with different experimental techniques and assays have generated a vast
      body of knowledge during the last decades. However, in recent years a type of
      assays, referred to as two-dimensional or membrane-to-membrane, has questioned
      our current understanding of the role of different kinetic constants (for
      instance, on- versus off-rate constants) on TCR-ligand interaction and subsequent
      T cell activation. Here we present a general mathematical framework that provides
      a unifying umbrella to relate fundamental and effective (or experimentally
      determined) kinetic constants, as well as describe and compare state-of-the-art
      experimental methods. Our framework is able to predict the correlations between
      functional output, such as 1/EC50, and effective kinetic constants for a range of
      different experimental assays (in two and three dimensions). Furthermore, our
      approach can be applied beyond Immunology, and serve as a "translation method"
      for the biochemical characterization of receptor-ligand interactions.

PMID- 28443631
TI  - A peripheral epigenetic signature of immune system genes is linked to neocortical
      thickness and memory.
AB  - Increasing age is tightly linked to decreased thickness of the human neocortex.
      The biological mechanisms that mediate this effect are hitherto unknown. The DNA
      methylome, as part of the epigenome, contributes significantly to age-related
      phenotypic changes. Here, we identify an epigenetic signature that is associated
      with cortical thickness (P=3.86 * 10-8) and memory performance in 533 healthy
      young adults. The epigenetic effect on cortical thickness was replicated in a
      sample comprising 596 participants with major depressive disorder and healthy
      controls. The epigenetic signature mediates partially the effect of age on
      cortical thickness (P<0.001). A multilocus genetic score reflecting genetic
      variability of this signature is associated with memory performance (P=0.0003) in
      3,346 young and elderly healthy adults. The genomic location of the contributing
      methylation sites points to the involvement of specific immune system genes. The
      decomposition of blood methylome-wide patterns bears considerable potential for
      the study of brain-related traits.

PMID- 28443636
TI  - Rich complex behaviour of self-assembled nanoparticles far from equilibrium.
AB  - A profoundly fundamental question at the interface between physics and biology
      remains open: what are the minimum requirements for emergence of complex
      behaviour from nonliving systems? Here, we address this question and report
      complex behaviour of tens to thousands of colloidal nanoparticles in a system
      designed to be as plain as possible: the system is driven far from equilibrium by
      ultrafast laser pulses that create spatiotemporal temperature gradients, inducing
      Marangoni flow that drags particles towards aggregation; strong Brownian motion,
      used as source of fluctuations, opposes aggregation. Nonlinear feedback
      mechanisms naturally arise between flow, aggregate and Brownian motion, allowing
      fast external control with minimal intervention. Consequently, complex behaviour,
      analogous to those seen in living organisms, emerges, whereby aggregates can self
      sustain, self-regulate, self-replicate, self-heal and can be transferred from one
      location to another, all within seconds. Aggregates can comprise only one pattern
      or bifurcated patterns can coexist, compete, endure or perish.

PMID- 28443638
TI  - Corrigendum: Recovery of Interdependent Networks.

PMID- 28443635
TI  - Expression and localisation of two-pore domain (K2P) background leak potassium
      ion channels in the mouse retina.
AB  - Two-pore domain (K2P) potassium channels perform essential roles in neuronal
      function. These channels produce background leak type potassium currents that act
      to regulate resting membrane potential and levels of cellular excitability. 15
      different K2P channels have been identified in mammals and these channels perform
      important roles in a wide number of physiological systems. However, to date there
      is only limited data available concerning the expression and role of K2P channels
      in the retina. In this study we conduct the first comprehensive study of K2P
      channel expression in the retina. Our data show that K2P channels are widely
      expressed in the mouse retina, with variations in expression detected at
      different times of day and throughout postnatal development. The highest levels
      of K2P channel expression are observed for Muller cells (TWIK-1, TASK-3, TRAAK,
      and TREK-2) and retinal ganglion cells (TASK-1, TREK-1, TWIK-1, TWIK-2 and TWIK
      3). These data offer new insight into the channels that regulate the resting
      membrane potential and electrical activity of retinal cells, and suggests that
      K2P channels are well placed to act as central regulators of visual signalling
      pathways. The prominent role of K2P channels in neuroprotection offers novel
      avenues of research into the treatment of common retinal diseases.

PMID- 28443639
TI  - Insect Immunity: Mechanism of adaptive immunity found in the fruitfly.

PMID- 28443637
TI  - Mild MPP+ exposure-induced glucose starvation enhances autophagosome synthesis
      and impairs its degradation.
AB  - Parkinson's disease (PD) is a prevalent neurodegenerative disorder, mainly
      characterised by the progressive loss of dopaminergic neurons. MPP+ has been
      widely used as a PD-related neurotoxin, and their reports suggested the several
      hypotheses for neuronal cell death. However, most of these hypotheses come from
      the studies about the acute MPP+ exposure. We previously revealed that mild MPP+
      exposure (10 and 200 MUM), which induces gradual cell death, impairs
      autophagosome degradation at 48 h. In the present study, we further investigated
      the specific events of mild MPP+ exposure and revealed that mild MPP+ exposure
      causes the cell death through glucose starvation, but not acute toxic model (2.5
      and 5 mM). At 36 h after mild MPP+ exposure, autophagosome synthesis was enhanced
      owing to glucose starvation and continued to enhance until 48 h, despite impaired
      autophagosome degradation. Inhibition of autophagosome synthesis reduced mild
      MPP+-induced cell death. In conclusion, we clarified that glucose starvation
      enhanced autophagosome synthesis occurs at an earlier stage than impaired
      autophagosome degradation and is important in mild MPP+ toxicity.

PMID- 28443640
TI  - Cytokines: Oncostatin M - a new target in IBD?

PMID- 28443641
TI  - Neuroimmunology: Immune signals packaged in the brain.

PMID- 28443642
TI  - Holey two-dimensional transition metal oxide nanosheets for efficient energy
      storage.
AB  - Transition metal oxide nanomaterials are promising electrodes for alkali-ion
      batteries owing to their distinct reaction mechanism, abundant active sites and
      shortened ion diffusion distance. However, detailed conversion reaction processes
      in terms of the oxidation state evolution and chemical/mechanical stability of
      the electrodes are still poorly understood. Herein we explore a general synthetic
      strategy for versatile synthesis of various holey transition metal oxide
      nanosheets with adjustable hole sizes that enable greatly enhanced alkali-ion
      storage properties. We employ in-situ transmission electron microscopy and
      operando X-ray absorption structures to study the mechanical properties,
      morphology evolution and oxidation state changes during electrochemical
      processes. We find that these holey oxide nanosheets exhibit strong mechanical
      stability inherited from graphene oxide, displaying minimal structural changes
      during lithiation/delithiation processes. These holey oxide nanosheets represent
      a promising material platform for in-situ probing the electrochemical processes,
      and could open up opportunities in many energy storage and conversion systems.

PMID- 28443625
TI  - Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour
      identifies novel loci for obesity traits.
AB  - Few genome-wide association studies (GWAS) account for environmental exposures,
      like smoking, potentially impacting the overall trait variance when investigating
      the genetic contribution to obesity-related traits. Here, we use GWAS data from
      51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify
      loci influencing BMI and central adiposity, measured as waist circumference and
      waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and
      9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity
      related traits. We show consistent direction of effect for all identified loci
      and significance for 18 novel and for 5 interaction loci in an independent study
      sample. These loci highlight novel biological functions, including response to
      oxidative stress, addictive behaviour, and regulatory functions emphasizing the
      importance of accounting for environment in genetic analyses. Our results suggest
      that tobacco smoking may alter the genetic susceptibility to overall adiposity
      and body fat distribution.

PMID- 28443643
TI  - FAF1 phosphorylation by AKT accumulates TGF-beta type II receptor and drives
      breast cancer metastasis.
AB  - TGF-beta is pro-metastatic for the late-stage breast cancer cells. Despite recent
      progress, the regulation of TGF-beta type II receptor remains uncertain. Here we
      report that FAF1 destabilizes TbetaRII on the cell surface by recruiting the
      VCP/E3 ligase complex, thereby limiting excessive TGF-beta response. Importantly,
      activated AKT directly phosphorylates FAF1 at Ser 582, which disrupts the FAF1
      VCP complex and reduces FAF1 at the plasma membrane. The latter results in an
      increase in TbetaRII at the cell surface that promotes both TGF-beta-induced SMAD
      and non-SMAD signalling. We uncover a metastasis suppressing role for FAF1
      through analyses of FAF1-knockout animals, various in vitro and in vivo models of
      epithelial-to-mesenchymal transition and metastasis, an MMTV-PyMT transgenic
      mouse model of mammary tumour progression and clinical breast cancer samples.
      These findings describe a previously uncharacterized mechanism by which TbetaRII
      is tightly controlled. Together, we reveal how SMAD and AKT pathways interact to
      confer pro-oncogenic responses to TGF-beta.

PMID- 28443645
TI  - Electronegativity determination of individual surface atoms by atomic force
      microscopy.
AB  - Electronegativity is a fundamental concept in chemistry. Despite its importance,
      the experimental determination has been limited only to ensemble-averaged
      techniques. Here, we report a methodology to evaluate the electronegativity of
      individual surface atoms by atomic force microscopy. By measuring bond energies
      on the surface atoms using different tips, we find characteristic linear
      relations between the bond energies of different chemical species. We show that
      the linear relation can be rationalized by Pauling's equation for polar covalent
      bonds. This opens the possibility to characterize the electronegativity of
      individual surface atoms. Moreover, we demonstrate that the method is sensitive
      to variation of the electronegativity of given atomic species on a surface due to
      different chemical environments. Our findings open up ways of analysing surface
      chemical reactivity at the atomic scale.

PMID- 28443646
TI  - On the dynamics and control of mechanical properties of hierarchical rotating
      rigid unit auxetics.
AB  - In this work, we investigate the deformation mechanism of auxetic hierarchical
      rotating square systems through a dynamics approach. We show how their
      deformation behaviour, hence their mechanical properties and final configuration
      for a given applied load, can be manipulated solely by altering the resistance to
      rotational motion of the hinges within the system. This provides enhanced
      tunability without necessarily changing the geometry of the system, a phenomenon
      which is not typically observed in other non-hierarchical unimode auxetic
      systems. This gives this hierarchical system increased versatility and tunability
      thus making it more amenable to be employed in practical application which may
      range from smart filtration to smart dressings.

PMID- 28443647
TI  - Identifying and modeling the structural discontinuities of human interactions.
AB  - The idea of a hierarchical spatial organization of society lies at the core of
      seminal theories in human geography that have strongly influenced our
      understanding of social organization. Along the same line, the recent
      availability of large-scale human mobility and communication data has offered
      novel quantitative insights hinting at a strong geographical confinement of human
      interactions within neighboring regions, extending to local levels within
      countries. However, models of human interaction largely ignore this effect. Here,
      we analyze several country-wide networks of telephone calls - both, mobile and
      landline - and in either case uncover a systematic decrease of communication
      induced by borders which we identify as the missing variable in state-of-the-art
      models. Using this empirical evidence, we propose an alternative modeling
      framework that naturally stylizes the damping effect of borders. We show that
      this new notion substantially improves the predictive power of widely used
      interaction models. This increases our ability to understand, model and predict
      social activities and to plan the development of infrastructures across multiple
      scales.

PMID- 28443648
TI  - The Rise and Fall of Disability Insurance Enrollment in the Netherlands.

PMID- 28443644
TI  - A reciprocal regulatory loop between TAZ/YAP and G-protein Galphas regulates
      Schwann cell proliferation and myelination.
AB  - Schwann cell (SC) myelination in the peripheral nervous system is essential for
      motor function, and uncontrolled SC proliferation occurs in cancer. Here, we show
      that a dual role for Hippo effectors TAZ and YAP in SC proliferation and
      myelination through modulating G-protein expression and interacting with SOX10,
      respectively. Developmentally regulated mutagenesis indicates that TAZ/YAP are
      critical for SC proliferation and differentiation in a stage-dependent manner.
      Genome-wide occupancy mapping and transcriptome profiling reveal that nuclear
      TAZ/YAP promote SC proliferation by activating cell cycle regulators, while
      targeting critical differentiation regulators in cooperation with SOX10 for
      myelination. We further identify that TAZ targets and represses Gnas, encoding
      Galphas-protein, which opposes TAZ/YAP activities to decelerate proliferation.
      Gnas deletion expands SC precursor pools and blocks peripheral myelination. Thus,
      the Hippo/TAZ/YAP and Galphas-protein feedback circuit functions as a fulcrum
      balancing SC proliferation and differentiation, providing insights into molecular
      programming of SC lineage progression and homeostasis.

PMID- 28443649
TI  - Disability Benefit Receipt and Reform: Reconciling Trends in the United Kingdom.

PMID- 28443650
TI  - Health Insurance and Income Inequality.

PMID- 28443651
TI  - The Economic Consequences of Family Policies: Lessons from a Century of
      Legislation in High-Income Countries.

PMID- 28443652
TI  - Electronic Properties of Graphene-PtSe2 Contacts.
AB  - In this article, we study the electronic properties of graphene in contact with
      monolayer and bilayer PtSe2 using first-principles calculations. It turns out
      that there is no charge transfer between the components because of the weak van
      der Waals interaction. We calculate the work functions of monolayer and bilayer
      PtSe2 and analyze the band bending at the contact with graphene. The formation of
      an n-type Schottky contact with monolayer PtSe2 and a p-type Schottky contact
      with bilayer PtSe2 is demonstrated. The Schottky barrier height is very low in
      the bilayer case and can be reduced to zero by 0.8% biaxial tensile strain.

PMID- 28443653
TI  - Borophane as a Benchmate of Graphene: A Potential 2D Material for Anode of Li and
      Na-Ion Batteries.
AB  - Borophene, single atomic-layer sheet of boron ( Science 2015 , 350 , 1513 ), is a
      rather new entrant into the burgeoning class of 2D materials. Borophene exhibits
      anisotropic metallic properties whereas its hydrogenated counterpart borophane is
      reported to be a gapless Dirac material lying on the same bench with the
      celebrated graphene. Interestingly, this transition of borophane also rendered
      stability to it considering the fact that borophene was synthesized under
      ultrahigh vacuum conditions on a metallic (Ag) substrate. On the basis of first
      principles density functional theory computations, we have investigated the
      possibilities of borophane as a potential Li/Na-ion battery anode material. We
      obtained a binding energy of -2.58 (-1.08 eV) eV for Li (Na)-adatom on borophane
      and Bader charge analysis revealed that Li(Na) atom exists in Li+(Na+) state.
      Further, on binding with Li/Na, borophane exhibited metallic properties as
      evidenced by the electronic band structure. We found that diffusion pathways for
      Li/Na on the borophane surface are anisotropic with x direction being the
      favorable one with a barrier of 0.27 and 0.09 eV, respectively. While assessing
      the Li-ion anode performance, we estimated that the maximum Li content is
      Li0.445B2H2, which gives rises to a material with a maximum theoretical specific
      capacity of 504 mAh/g together with an average voltage of 0.43 V versus Li/Li+.
      Likewise, for Na-ion the maximum theoretical capacity and average voltage were
      estimated to be 504 mAh/g and 0.03 V versus Na/Na+, respectively. These findings
      unambiguously suggest that borophane can be a potential addition to the map of Li
      and Na-ion anode materials and can rival some of the recently reported 2D
      materials including graphene.

PMID- 28443654
TI  - Quantifying the Self-Assembly Behavior of Anisotropic Nanoparticles Using Liquid
      Phase Transmission Electron Microscopy.
AB  - For decades, one of the overarching objectives of self-assembly science has been
      to define the rules necessary to build functional, artificial materials with rich
      and adaptive phase behavior from the bottom-up. To this end, the computational
      and experimental efforts of chemists, physicists, materials scientists, and
      biologists alike have built a body of knowledge that spans both disciplines and
      length scales. Indeed, today control of self-assembly is extending even to
      supramolecular and molecular levels, where crystal engineering and design of
      porous materials are becoming exciting areas of exploration. Nevertheless, at
      least at the nanoscale, there are many stones yet to be turned. While recent
      breakthroughs in nanoparticle (NP) synthesis have amassed a vast library of
      nanoscale building blocks, NP-NP interactions in situ remain poorly quantified,
      in large part due to technical and theoretical impediments. While increasingly
      many applications for self-assembled architectures are being demonstrated, it
      remains difficult to predict-and therefore engineer-the pathways by which these
      structures form. Here, we describe how investigations using liquid-phase
      transmission electron microscopy (TEM) have begun to play a role in pursuing some
      of these long-standing questions of fundamental and far-reaching interest. Liquid
      phase TEM is unique in its ability to resolve the motions and trajectories of
      single NPs in solution, making it a powerful tool for studying the dynamics of NP
      self-assembly. Since 2012, liquid-phase TEM has been used to investigate the self
      assembly behavior of a variety of simple, metallic NPs. In this Account, however,
      we focus on our work with anisotropic NPs, which we show to have very different
      self-assembly behavior, and especially on how analysis methods we and others in
      the field are developing can be used to convert their motions and trajectories
      revealed by liquid-phase TEM into quantitative understanding of underlying
      interactions and dynamics. In general, liquid-phase TEM studies may help bridge
      enduring gaps in the understanding and control of self-assembly at the nanoscale.
      For one, quantification of NP-NP interactions and self-assembly dynamics will
      inform both computational and statistical mechanical models used to describe
      nanoscale phenomena. Such understanding will also lay the groundwork for
      establishing new and generalizable thermodynamic and kinetic design rules for NP
      self-assembly. Synergies with NP synthesis will enable investigations of building
      blocks with novel, perhaps even evolving or active behavior. Moreover, in the
      long run, we foresee the possibility of applying the guidelines and models of
      fundamental nanoscale interactions which are uncovered under liquid-phase TEM to
      biological and biomimetic systems at similar dimensions.

PMID- 28443655
TI  - New Insights on Electro-Optical Response of Poly(3,4
      ethylenedioxythiophene):Poly(styrenesulfonate) Film to Humidity.
AB  - Understanding the relative humidity (RH) response of poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is critical for
      improving the stability of organic electronic devices and developing selective
      sensors. In this work, combined gravimetric sensing, nanoscale surface probing,
      and mesoscale optoelectronic characterization are used to directly compare the RH
      dependence of electrical and optical conductivities and unfold connections
      between the rate of water adsorption and changes in functional properties of
      PEDOT:PSS film. We report three distinct regimes where changes in electrical
      conductivity, optical conductivity, and optical bandgap are correlated with the
      mass of adsorbed water. At low (RH < 25%) and high (RH > 60%) humidity levels,
      dramatic changes in electrical, optical, and structural properties occur, while
      changes are insignificant in mid-RH (25 < RH < 60%) conditions. We associate the
      three regimes with water adsorption at hydrophilic moieties at low RH, diffusion
      and swelling throughout the film at mid-RH, and saturation of the film by water
      at high RH. Optical film thickness increased by 150% as RH was increased from 9
      to 80%. Low frequency (1 kHz) impedance increased by ~100%, and film capacitance
      increased by ~30% as RH increased from 9 to 80% due to an increase in the film
      dielectric constant. Changes in electrical and optical conductivities
      concomitantly decrease across the full range of RH tested.

PMID- 28443656
TI  - Acyl Fluorides: Fast, Efficient, and Versatile Lysine-Based Protein Conjugation
      via Plug-and-Play Strategy.
AB  - We report a plug-and-play strategy for the preparation of functionally enhanced
      antibodies with a defined average degree of conjugation (DoC). The first stage
      (plug) allows the controllable and efficient installation of azide groups on
      lysine residues of a native antibody using 4-azidobenzoyl fluoride. The second
      step (play) allows for versatile antibody functionalization with a single payload
      or combination of payloads, such as a toxin, a fluorophore, or an
      oligonucleotide, via copper-free strain-promoted azide-alkyne cycloaddition
      (SPAAC). It is notable that in comparison to a classical N-hydroxysuccinimide
      ester (NHS) strategy, benzoyl fluorides show faster and more efficient acylation
      of lysine residues in a PBS buffer. This translates into better control of the
      DoC and enables the efficient and fast functionalization of delicate biomolecules
      at low temperature.

PMID- 28443657
TI  - Characterization of Sputter-Deposited LiCoO2 Thin Film Grown on NASICON-type
      Electrolyte for Application in All-Solid-State Rechargeable Lithium Battery.
AB  - All-solid-state Li-rechargeable batteries using a 500 nm-thick LiCoO2 (LCO) film
      deposited on two NASICON-type solid electrolyte substrates, LICGC (OHARA Inc.)
      and Li1.3Al0.3Ti1.7(PO4)3 (LATP), are constructed. The postdeposition annealing
      temperature prior to the cell assembly is critical to produce a stable sharp
      LCO/electrolyte interface and to develop a strong crystallographic texture in the
      LCO film, conducive to migration of Li ions. Although the cells deliver a limited
      discharge capacity, the cells cycled stably for 50 cycles. The analysis of the
      LCO/electrolyte interfaces after cycling demonstrates that the sharp interface,
      once formed by proper thermal annealing, will remain stable without any evidence
      for contamination and with minimal intermixing of the constituent elements during
      cycling. Hence, although ionic conductivity of the NASICON-type solid electrolyte
      is lower than that of the sulfide electrolytes, the NACSICON-type electrolytes
      will maintain a stable interface in contact with a LCO cathode, which should be
      beneficial to improving the capacity retention as well as the rate capability of
      the all-solid state cell.

PMID- 28443658
TI  - DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the
      Metabolic Pathway for Biosynthesis of Chemicals.
AB  - Chemical synthesis is a well established route for producing many chemicals on a
      large scale, but some drawbacks still exist in this process, such as unstable
      intermediates, multistep reactions, complex process control, etc. Biobased
      production provides an attractive alternative to these challenges, but how to
      make cells into efficient factories is challenging. As a key enabling technology
      to develop efficient cell factories, design-construction-evaluation-optimization
      (DCEO) biotechnology, which incorporates the concepts and techniques of pathway
      design, pathway construction, pathway evaluation, and pathway optimization at the
      systems level, offers a conceptual and technological framework to exploit
      potential pathways, modify existing pathways and create new pathways for the
      optimal production of desired chemicals. Here, we summarize recent progress of
      DCEO biotechnology and examples of its application, and provide insights as to
      when, what and how different strategies should be taken. In addition, we
      highlight future perspectives of DCEO biotechnology for the successful
      establishment of biorefineries.

PMID- 28443659
TI  - New Class of Half-Sandwich Ruthenium(II) Arene Complexes Bearing the Water
      Soluble CAP Ligand as an in Vitro Anticancer Agent.
AB  - Ruthenium(II) arene complexes of 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane
      (CAP) were obtained. Cytotoxicity studies against cancer cell lines reveal higher
      activity than the corresponding PTA analogues and, in comparison to the effects
      on noncancerous cells, the complexes are endowed with a reasonable degree of
      cancer cell selectivity.

PMID- 28443660
TI  - Assessing the Risk of Engineered Nanomaterials in the Environment: Development
      and Application of the nanoFate Model.
AB  - We developed a dynamic multimedia fate and transport model (nanoFate) to predict
      the time-dependent accumulation of metallic engineered nanomaterials (ENMs)
      across environmental media. nanoFate considers a wider range of processes and
      environmental subcompartments than most previous models and considers ENM
      releases to compartments (e.g., urban, agriculture) in a manner that reflects
      their different patterns of use and disposal. As an example, we simulated ten
      years of release of nano CeO2, CuO, TiO2, and ZnO in the San Francisco Bay area.
      Results show that even soluble metal oxide ENMs may accumulate as nanoparticles
      in the environment in sufficient concentrations to exceed the minimum toxic
      threshold in freshwater and some soils, though this is more likely with high
      production ENMs such as TiO2 and ZnO. Fluctuations in weather and release
      scenario may lead to circumstances where predicted ENM concentrations approach
      acute toxic concentrations. The fate of these ENMs is to mostly remain either
      aggregated or dissolved in agricultural lands receiving biosolids and in
      freshwater or marine sediments. Comparison to previous studies indicates the
      importance of some key model aspects including climatic and temporal variations,
      how ENMs may be released into the environment, and the effect of compartment
      composition on predicted concentrations.

PMID- 28443661
TI  - Engineering of RuMb: Toward a Green Catalyst for Carbene Insertion Reactions.
AB  - The small, stable heme protein myoglobin (Mb) was modified through cofactor
      substitution and mutagenesis to develop a new catalyst for carbene transfer
      reactions. The native heme was removed from wild-type Mb and several Mb His64
      mutants (H64D, H64A, H64V), and the resulting apoproteins were reconstituted with
      ruthenium mesoporphyrin IX (RuMpIX). The reconstituted proteins (RuMb) were
      characterized by UV-vis and circular dichroism spectroscopy and were used as
      catalysts for the N-H insertion of aniline derivatives and the cyclopropanation
      of styrene derivatives. The best catalysts for each reaction were able to achieve
      turnover numbers (TON) up to 520 for the N-H insertion of aniline, and 350 TON
      for the cyclopropanation of vinyl anisole. Our results show that RuMb is an
      effective catalyst for N-H insertion, with the potential to further increase the
      activity and stereoselectivity of the catalyst in future studies. Compared to
      native Mb ("FeMb"), RuMb is a more active catalyst for carbene transfer
      reactions, which leads to both heme and protein modification and degradation and,
      hence, to an overall much-reduced lifetime of the catalyst. This leads to lower
      TONs for RuMb compared to the iron-containing analogues. Strategies to overcome
      this limitation are discussed. Finally, comparison is also made to FeH64DMb and
      FeH64AMb, which have not been previously investigated for carbene transfer
      reactions.

PMID- 28443662
TI  - Bis(tert-butylimido)bis(N,O-chelate)tungsten(VI) Complexes: Probing Amidate and
      Pyridonate Hemilability.
AB  - Four new bis(tert-butylimido)bis(N,O-chelate)tungsten(VI) complexes (3-6), in
      which the N,O-chelate is an amidate or pyridonate ligand, have been synthesized
      and characterized. Computational analysis has been used to calculate the relative
      energies of different stereoisomers and shown how the steric demand of each
      ligand influences coordination and bonding modes. The electronically saturated
      complexes have been employed to evaluate 1,3-N,O-chelated metal-ligand
      interactions. Complexes 3-6 were treated with electrophilic reagents, which
      resulted in strikingly different reactivity patterns between the amidate and the
      pyridonate ligated complexes. The observed reactivity differences are accompanied
      by direct observation of different trends in the hemilability of these two
      different classes of 1,3-N,O-chelates.

PMID- 28443663
TI  - Host-Guest Interactions Accompanying the Encapsulation of 1,4
      Diazabicyclo[2.2.2]octane within endo-Functionalized Macrocycles.
AB  - The binding of novel endofunctionalized bis-urea/thiourea molecular receptors
      toward neutral 1,4-diazabicyclo[2.2.2]octane (DABCO) demonstrates stronger
      binding of the bis-thiourea macrocycles than for their urea analogues by
      employing M06-2X/6-31+G(d,p)-based density functional theory. The formation of
      such inclusion complexes is spontaneous, thermodynamically favorable, and
      facilitated via bifurcated N-H...N...H-N hydrogen bonding and C-H...pi, dipole
      dipole, and other noncovalent interactions, which are reflected in the frequency
      shift of their characteristic N-H vibrations in the calculated vibrational
      spectra of these complexes. The underlying noncovalent interactions are analyzed
      using the molecular electrostatic potential topography and quantum theory of
      atoms in molecules in conjunction with the noncovalent interactions reduced
      density gradient method. It has also been shown that the encapsulation of DABCO
      within the pi-electron-rich cavity of such hosts brings about shielding of the
      guest protons confined within the host cavity whereas those facilitating hydrogen
      bonding engender the downfield signals in their calculated 1H NMR spectra.

PMID- 28443664
TI  - Theory and Electrochemistry of Cytochrome c.
AB  - Extensive simulations of cytochrome c in solution are performed to address the
      apparent contradiction between large reorganization energies of protein electron
      transfer typically reported by atomistic simulations and much smaller values
      produced by protein electrochemistry. The two sets of data are reconciled by
      deriving the activation barrier for electrochemical reaction in terms of an
      effective reorganization energy composed of half the Stokes shift (characterizing
      the medium polarization in response to electron transfer) and the variance
      reorganization energy (characterizing the breadth of electrostatic fluctuations).
      This effective reorganization energy is much smaller than each of the two
      components contributing to it and is fully consistent with electrochemical
      measurements. Calculations in the range of temperatures between 280 and 360 K
      combine long, classical molecular dynamics simulations with quantum calculations
      of the protein active site. The results agree with the Arrhenius plots for the
      reaction rates and with cyclic voltammetry of cytochrome c immobilized on self
      assembled monolayers. Small effective reorganization energy, and the resulting
      small activation barrier, is a general phenomenology of protein electron transfer
      allowing fast electron transport within biological energy chains.

PMID- 28443665
TI  - Octakis(2-pyridyl)porphyrazine and Its Neutral Metal Derivatives: UV-Visible
      Spectral, Electrochemical, and Photoactivity Studies.
AB  - Tetrapyrrolic porphyrazine macrocycles with externally appended 2-pyridyl rings
      were synthesized and characterized as to their spectroscopic, electrochemical,
      and photophysical properties. The investigated compounds are represented as
      [Py8PzH2], the unmetalated octakis(2-pyridyl)porphyrazine, and the metal
      complexes [Py8PzM], where M is MgII(H2O), CuII, ZnII, or CoII. The spectroscopic
      properties and the electrochemical behavior of these compounds were examined in
      solution of polar (pyridine, dimethyl sulfoxide, and dimethylformamide) and
      nondonor solvents (CHCl3, CH2Cl2), and the data were compared with those obtained
      from earlier studies on the related tetrapyrazinoporphyrazines, [Py8TPyzPzM], and
      the tetraquinoxalinoporphyrazines, [Py8QxPzM], also bearing externally 2-pyridyl
      rings, and characterized by a more extended central pi-conjugated macrocyclic
      framework. The newly synthesized porphyrazines possess good solubility and are
      present in their monomeric form in all the examined solvents as shown by UV
      visible spectra. The unmetalated species and metal derivatives undergo multiple
      one-electron reductions within the potential range of the nonaqueous examined
      solvents. The derivatives with nonredox active metal centers could accept four
      electrons on the conjugated macrocycle, while the CoII complex was characterized
      by a single one-electron oxidation and five reductions in DMSO. The
      photosensitizer activity for the generation of singlet oxygen was also examined
      for the MgII(H2O) and ZnII complexes in DMF, with measured PhiDelta values being,
      respectively, 0.42 and 0.64, this latter value indicating the ZnII species as
      being a promising material for use as anticancer agent in photodynamic therapy.

PMID- 28443666
TI  - Correction to "Artifact-Free and Detection-Profile-Independent Higher-Order
      Fluorescence Correlation Spectroscopy for Microsecond-Resolved Kinetics. 2.
      Mixtures and Reactions".

PMID- 28443667
TI  - Identification of a Phosphodiesterase-Inhibiting Fraction from Roasted Coffee
      (Coffea arabica) through Activity-Guided Fractionation.
AB  - Recent reports that coffee can significantly inhibit cAMP phosphodiesterases
      (PDEs) in vitro, as well as in vivo, have described another beneficial effect of
      coffee consumption. However, the PDE-inhibiting substances remain mostly unknown.
      We chose activity-guided fractionation and an in vitro test system to identify
      the coffee components that are responsible for PDE inhibition. This approach
      indicated that a fraction of melanoidins reveals strong PDE-inhibiting potential
      (IC50 = 130 +/- 42 MUg/mL). These melanoidins were characterized as water
      soluble, low-molecular weight melanoidins (<3 kDa) with a nitrogen content of
      4.2% and a carbohydrate content lower than those of other melanoidins. Fractions
      containing known PDE inhibitors such as chlorogenic acids, alkylpyrazines, or
      trigonelline as well as N-caffeoyl-tryptophan and N-p-coumaroyl-tryptophan did
      not exert PDE-inhibiting activity. We also observed that the known PDE inhibitor
      caffeine does not contribute to the PDE-inhibiting effects of coffee.

PMID- 28443668
TI  - Tungsten(VI)-Copper(I)-Sulfur Cluster-Supported Metal-Organic Frameworks Bridged
      by in Situ Click-Formed Tetrazolate Ligands.
AB  - Six analogous two-dimensional (2D) [Tp*WS3Cu3]-based (Tp* = hydridotris(3,5
      dimethylpyrazol-1-yl)borate) networks, namely, {[(Tp*WS3Cu3)2L3](MU3-N3)}n (2: L
      = 5-methyltetrazolate (Mtta); 3a: L = 5-ethyltetrazolate (Etta)) and
      {[(Tp*WS3Cu3)2L3]BF4}n (3b: L = Etta; 4: L = 5-propyltetrazolate (Ptta); 5: L = 5
      butyltetrazolate (Btta); 6: L = 5-pentyltetrazolate (Petta)) were synthesized by
      reactions of [Et4N][Tp*WS3] (1), [Cu(CH3CN)4]BF4, NaN3, and NH4BF4 in different
      nitrile solvents (CH3(CH2)nCN, n = 0, 1, 2, 3, and 4) under solvothermal
      conditions. In the structures of 2-6, each alkyl tetrazolate L as a bridging
      ligand was generated in situ from the "click" reaction between azide and nitrile.
      These 2D (6,3) networks support two types of voids wherein the pendant alkyl
      groups are accommodated. A tetrahedron cage-like cluster [Tp*W(MU3-S)3(MU3
      S')Cu3]4 (7) was also formed in some of the above reactions and can be readily
      separated by solvent extraction. The proportion of 7 increased with the
      elongation of the alkyl chains and finally became the exclusive product when
      heptylnitrile was employed. Further use of CuCN as a surrogate for
      [Cu(CH3CN)4]BF4 with the aim of introducing additional CN bridges into the
      network led us to isolate a tetrazolate-free compound,
      {[Et4N]{(Tp*WS3Cu3)[Cu2(CN)4.5]}2.2PhCH2CN}n (8.2PhCH2CN), a unique 2D network
      that features {(Tp*WS3Cu3)[Cu2(CN)5]}22-, {(Tp*WS3Cu3)3[Cu3(CN)7]2[Cu(CN)3]}4-,
      and {(Tp*WS3Cu3)[Cu4(CN)9]}26- ring subunits. Compounds 5-8 are soluble in DMF
      and exhibit a reverse saturable absorption and self-focusing third-order
      nonlinear optical (NLO) effect at 532 nm with hyperpolarizability gamma values in
      the range of 4.43 * 10-30 to 5.40 * 10-30 esu, which are 400-500 times larger
      than that of their precursor 1. The results provide an interesting insight into
      the synergetic synthetic strategy related to the assembly of the [Tp*WS3Cu3]2+
      cluster core, the "click" formation of the tetrazolate ligands, and the
      construction of the [Tp*WS3Cu3]2+ cluster-based 2D networks.

PMID- 28443669
TI  - PPh3-Catalyzed [3 + 2] Spiroannulation of 1C,3N-Bisnucleophiles Derived from
      Secondary beta-Ketoamides with delta-Acetoxy Allenoate: A Route to Functionalized
      Spiro N-Heterocyclic Derivatives.
AB  - A [3 + 2] annulation of alpha-substituted secondary beta-ketoamides with delta
      acetoxy-modified allenoate has been developed in the presence of phosphine
      catalyst. In this spiroannulation reaction, beta-ketoamides were used as the bis
      nucleophilic partner while the gamma,delta-carbon of 5-acetoxypenta-2,3-dienoate
      participated as a C2 synthon, affording the desired functionalized five-membered
      N-heterocyclic derivatives in moderate to excellent yields and
      diastereoselectivities under mild conditions. Preliminary attempts on the
      asymmetric variant of this reaction have been also examined, giving the
      corresponding products with moderate ee values.

PMID- 28443670
TI  - Cooperativity in Alcohol-Nitrogen Complexes: Understanding Cryomatrices through
      Slit Jet Expansions.
AB  - FTIR spectroscopy of supersonic expansions is used to characterize alcohol dimers
      with one, two, and several nitrogen molecules attached to them. The nitrogen
      coating causes progressive spectral downshifts of the OH stretching fundamentals
      which are related to and explain matrix isolation shifts. Comparison of methanol,
      tert-butyl alcohol and ethanol as well as deuteration of methanol assist in the
      assignment. Alcohol monomers and trimers are significantly more resistant to
      nitrogen coating due to a lack of cooperativity and dangling bonds, respectively.
      In the case of ethanol, the role of conformational isomerism and combination
      bands is further elucidated. The experimental findings help rationalize the
      anomalously small OH stretching dimerization shift of methanol in the gas phase,
      in comparison to that of tert-butyl alcohol.

PMID- 28443671
TI  - Total Synthesis of Tanshinone I.
AB  - A novel total synthesis of tanshinone I (1) via the intermediate 3-hydroxy-8
      methyl-1,4-phenanthrenedione (8) is described. The low overall yields and the use
      of expensive reagents in the synthesis process were minimized by the use of the
      Diels-Alder reaction to directly construct the 1,4-phenanthrenedione scaffold,
      providing tanshinone I (1) in only three steps.

PMID- 28443672
TI  - Short Communication: Heightened HIV Antibody Responses in Postpartum Women as
      Exemplified by Recent Infection Assays: Implications for Incidence Estimates.
AB  - Laboratory assays that identify recent HIV infections are important for assessing
      impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral
      responses can vary with inherent assay properties, and between HIV subtypes,
      populations, and physiological states. They are important in determining mean
      duration of recent infection (MDRI) for antibody-based assays for detecting
      recent HIV infections. We determined MDRIs for multi-subtype peptide representing
      subtypes B, E and D (BED)-capture enzyme immunoassay, limiting antigen (LAg), and
      Bio-Rad Avidity Incidence (BRAI) assays for 101 seroconverting postpartum women,
      recruited in Harare from 1997 to 2000 during the Zimbabwe Vitamin A for Mothers
      and Babies trial, comparing them against published MDRIs estimated from
      seroconverting cases in the general population. We also compared MDRIs for women
      who seroconverted either during the first 9 months, or at later stages,
      postpartum. At cutoffs (C) of 0.8 for BED, 1.5 for LAg, and 40% for BRAI,
      estimated MDRIs for postpartum mothers were 192, 104, and 144 days, 33%, 32%, and
      52% lower than published estimates of 287, 152 and 298 days, respectively, for
      clade C samples from general populations. Point estimates of MDRI values were 7%
      19% shorter for women who seroconverted in the first 9 months postpartum than for
      those seroconverting later. MDRI values for three HIV incidence biomarkers are
      longer in the general population than among postpartum women, particularly those
      who recently gave birth, consistent with heightened immunological activation soon
      after birth. Our results provide a caution that MDRI may vary significantly
      between subjects in different physiological states.

PMID- 28443674
TI  - Perinatal Bacterial Exposure Contributes to IL-13 Aeroallergen Response.
AB  - There is a high prevalence of aeroallergen sensitivity in asthmatic populations,
      and seroreactivity to aeroallergens early in infancy is associated with increased
      risk of developing asthma later in life. In addition to allergen sensitivity,
      asthma development has been associated with differential microbial exposure and
      infection in early life. We have previously shown that cord blood mononuclear
      cells respond to common aeroallergens (i.e., house dust mite [Der f1] and
      cockroach [Bla g2]) as assayed by lymphoproliferation and cytokine (IL-13 and IFN
      gamma) production. We hypothesized that there is a relationship between perinatal
      microbial exposure and response to specific aeroallergens. To test this
      hypothesis, we isolated DNA from cord blood serum samples with known
      lymphoproliferative and cytokine responses to Bla g2 and Der f1. Bacterial 16S
      ribosomal DNA amplicon libraries were generated and analyzed using high
      throughput sequencing of cord blood serum samples. In our analysis, we identified
      major compositional differences, including diversity and abundance of specific
      taxa, between groups whose IL-13 response to Der f1 and Bla g2 differed. We
      demonstrate a strong association between the ratio of Acinetobacter to
      Proteobacteria and IL-13 production and the probability of IL-13 production after
      allergen exposure. IL-13 concentrations in serum were also significantly
      correlated with the diversity of bacterial DNA. Together, these results
      underscore the relationship between immune responses to allergens and bacterial
      exposure during perinatal development.

PMID- 28443673
TI  - Fluorescent Probes and Selective Inhibitors for Biological Studies of Hydrogen
      Sulfide- and Polysulfide-Mediated Signaling.
AB  - SIGNIFICANCE: Hydrogen sulfide (H2S) plays roles in many physiological processes,
      including relaxation of vascular smooth muscles, mediation of neurotransmission,
      inhibition of insulin signaling, and regulation of inflammation. Also,
      hydropersulfide (R-S-SH) and polysulfide (-S-Sn-S-) have recently been identified
      as reactive sulfur species (RSS) that regulate the bioactivities of multiple
      proteins via S-sulfhydration of cysteine residues (protein Cys-SSH) and show
      cytoprotection. Chemical tools such as fluorescent probes and selective
      inhibitors are needed to establish in detail the physiological roles of H2S and
      polysulfide. Recent Advances: Although many fluorescent probes for H2S are
      available, fluorescent probes for hydropersulfide and polysulfide have only
      recently been developed and used to detect these sulfur species in living cells.
      CRITICAL ISSUES: In this review, we summarize recent progress in developing
      chemical tools for the study of H2S, hydropersulfide, and polysulfide, covering
      fluorescent probes based on various design strategies and selective inhibitors of
      H2S- and polysulfide-producing enzymes (cystathionine gamma-lyase, cystathionine
      beta-synthase, and 3-mercaptopyruvate sulfurtransferase), and we summarize their
      applications in biological studies. FUTURE DIRECTIONS: Despite recent progress,
      the precise biological functions of H2S, hydropersulfide, and polysulfide remain
      to be fully established. Fluorescent probes and selective inhibitors are
      effective chemical tools to study the physiological roles of these sulfur
      molecules in living cells and tissues. Therefore, further development of a broad
      range of practical fluorescent probes and selective inhibitors as tools for
      studies of RSS biology is currently attracting great interest. Antioxid. Redox
      Signal. 27, 669-683.

PMID- 28443675
TI  - The Effect of Trigger Finger Injection Site on Injection-Related Pain.
AB  - BACKGROUND: Stenosing tenosynovitis, or trigger digit, is a common condition for
      which patients often seek relief. Corticosteroid injections have been shown to
      provide relief in many cases, and several different approaches for delivering the
      injection have been described in the literature. We compared patients' perception
      of pain following each of 3 accepted injection methods, namely, palmar proximal,
      palmar distal, and webspace approaches. METHODS: We prospectively followed 38
      patients with 39 symptomatic digits in this trial, with varying severities of
      trigger finger as graded by the Patel and Moradia classification. The patients
      were divided into 3 groups representing the 3 approaches without randomization,
      based upon the treating surgeons' preference. Disabilities of the Arm, Shoulder
      and Hand and visual analog scale (VAS) pain scores were calculated pre-injection
      and at 4-week and 8-week follow-up visits. RESULTS: No statistically significant
      differences in age, sex, affected extremity, grade, or duration of symptoms were
      observed among the 3 approaches. No statistically significant differences in VAS
      score were found between the palmar proximal (mean = 6.6, SD = 2.6), palmar
      distal (mean = 6.0, SD = 2.8), and webspace (mean = 6.8, SD = 1.8) approaches.
      CONCLUSION: Our data suggest that injection approach does not affect patient pain
      perception scores or outcomes. We recommend that the technique that is most
      comfortable to the surgeon be utilized, with the understanding that one injection
      alone has a low likelihood of relieving symptoms.

PMID- 28443676
TI  - Preoperative Nomograms for Predicting Renal Function at 1 Year After Partial
      Nephrectomy.
AB  - INTRODUCTION: Partial nephrectomy (PN) reduces the risk of postoperative chronic
      renal insufficiency (CRI). However, some patients still develop CRI after PN, and
      may eventually require dialysis. Being able to predict renal function before PN
      helps in counseling patients and managing expectations. We aimed to construct
      nomograms that predict estimated glomerular filtration rates (eGFRs), defined by
      the modification of diet in renal disease (MDRD) and the chronic kidney disease
      epidemiology collaboration (CKD-EPI) formulae, at 1 year after PN, using only
      preoperative covariates as predictors. PATIENTS AND METHODS: We identified
      patients who underwent PN in our institution between 2004 and 2016, with known
      postoperative serum creatinine levels at 1 year. The preoperative covariates
      included patients' demographics, chronic comorbid conditions, tumor
      characteristics, and preoperative renal status. The endpoints were eGFRs at 1
      year after PN, calculated using the MDRD and the CKD-EPI formulae. We first
      identified preoperative covariates with significant associations with the
      endpoints by Pearson correlation and independent samples t-test. Suitable
      covariates were then included in two multivariate linear regression models, for
      constructing and internally validating two nomograms. RESULTS: 461 patients were
      eligible for analysis. The percentage of patients with eGFR below 60 mL/min/1.73
      m2 increased from 25% before PN to 35% at 1 year after PN. We included age,
      gender, African American race, body mass index, preoperative creatinine level,
      ipsilateral renal volume, solitary kidney status, tumor diameter, hypertension,
      diabetes, ischemic heart disease, and previous stroke in the multivariate linear
      regression models for nomogram construction. Internal validation showed bootstrap
      corrected coefficients of determination of 0.61 and 0.70, for predicting eGFRs
      defined by the MDRD and CKD-EPI formulae, respectively. CONCLUSIONS: We
      constructed and internally validated two nomograms to predict eGFRs at 1 year
      after PN, using only preoperative covariates as predictors.

PMID- 28443677
TI  - Beyond social support: Self-care confidence is key for adherence in patients with
      heart failure.
AB  - BACKGROUND: Adherence to treatment is crucial to improve outcomes in patients
      with heart failure. Good social support is associated with better adherence, but
      the mechanism for this association has not been well-explored. AIMS: The aim of
      this secondary analysis was to examine whether self-care confidence mediates the
      relationship between social support and treatment adherence in heart failure
      patients hospitalized with acute exacerbation. METHODS: A total of 157 inpatients
      with heart failure (63.5+/-13 years, 73% New York Heart Association class III/IV)
      were recruited from two hospitals located in urban areas in the USA. Participants
      completed the Self-Care of Heart Failure Index, the Multidimensional Perceived
      Social Support Scale, and the Medical Outcomes Study Specific Adherence Scale. A
      series of regression models were used to determine the mediation relationship.
      RESULTS: Controlling for marital status and hospital site, social support was
      associated with adherence ( p=0.03). When self-confidence was included in the
      model, the effect of social support became non-significant, indicating full
      mediation of the relationship between social support and adherence by self-care
      confidence. The indirect effect (0.04) of social support on adherence through
      self-confidence was significant (95% confidence interval: 0.01-0.09). CONCLUSION:
      Heart failure self-care confidence mediated the relationship between social
      support and treatment adherence. Thus interventions targeting patients' self-care
      confidence is essential to maximize patients' treatment adherence.

PMID- 28443678
TI  - Outcomes Along the HIV Care Continuum Among Undocumented Immigrants in Clinical
      Care.
AB  - HIV-infected undocumented immigrants face unique barriers to care yet little is
      known about their clinical outcomes. We performed a retrospective cohort study of
      HIV-infected adults in clinical care from 2006 to 2014 at a large academic
      medical center in a setting where medical insurance is available to HIV-infected
      undocumented immigrants. Undocumented status was assessed based on Social
      Security number and insurance status and verified through medical chart review.
      Using Poisson regression models, we compared undocumented and documented patients
      with respect to retention in care (>=2 HIV-related laboratory tests >=90 days
      apart), antiretroviral therapy (ART) prescription (>=3 active antiretroviral
      agents prescribed in a year), and viral suppression (HIV RNA <200 copies/ml for
      the last measured viral load) for each year in care. Of 7,551 patients included
      in the analysis, we classified 173 (2.3%) as undocumented. For each year of the
      analysis, higher proportions of undocumented patients were retained in care,
      prescribed ART, and virally suppressed. In adjusted models, undocumented status
      was associated with increased probability of retention in care [risk ratio (RR)
      1.05, confidence interval (95% CI) 1.01-1.09], ART prescription (RR 1.05, 95% CI
      1.01-1.08), and viral suppression (RR 1.13, 95% CI 1.08-1.19) compared to
      documented status. Undocumented patients achieved clinical outcomes at modestly
      higher rates than documented patients, despite entering care with more advanced
      disease. In a setting where insurance is available to undocumented patients,
      similar outcomes along the HIV care continuum may be achieved regardless of
      immigration status.

PMID- 28443680
TI  - Periodic Breathing during Incremental Exercise.
AB  - Periodic breathing during incremental cardiopulmonary exercise testing is a
      regularly recurring waxing and waning of tidal volume due to oscillations in
      central respiratory drive. Periodic breathing is a sign of respiratory control
      system instability, which may occur at rest or during exercise. The possible
      mechanisms responsible for exertional periodic breathing might be related to any
      instability of the ventilatory regulation caused by: (1) increased circulatory
      delay (i.e., circulation time from the lung to the brain and chemoreceptors due
      to reduced cardiac index leading to delay in information transfer), (2) increase
      in controller gain (i.e., increased central and peripheral chemoreceptor
      sensitivity to arterial partial pressure of oxygen and of carbon dioxide), or (3)
      reduction in system damping (i.e., baroreflex impairment). Periodic breathing
      during exercise is observed in several cardiovascular disease populations, but it
      is a particularly frequent phenomenon in heart failure due to systolic
      dysfunction. The detection of exertional periodic breathing is linked to outcome
      and heralds worse prognosis in heart failure, independently of the criteria
      adopted for its definition. In small heart failure cohorts, exertional periodic
      breathing has been abolished with several dedicated interventions, but results
      have not yet been confirmed. Accordingly, further studies are needed to define
      the role of visceral feedbacks in determining periodic breathing during exercise
      as well as to look for specific tools for preventing/treating its occurrence in
      heart failure.

PMID- 28443681
TI  - Preventing the Forgotten Ureteral Stent by Using a Mobile Point-of-Care
      Application.
AB  - INTRODUCTION: The forgotten ureteral stent (FUS) can lead to patient morbidity.
      To date, tracking ureteral stents is a cumbersome task, given their high
      frequency of insertion and variable indwelling times. To simplify this process,
      an application was developed to track patients with indwelling ureteral stents.
      We report our initial user experience and clinical outcomes with this
      application. METHODS: Ureteral Stent TrackerTM (UST) is a secure, Health
      Insurance Portability and Accountability Act (HIPPA)-compliant, cloud-based point
      of-care application. It is designed for logging stent insertion, scheduling the
      date of anticipated stent extraction, and confirming stent removal. It is
      accessible via a mobile phone application or web browser interface. We
      consecutively enrolled all patients who underwent ureteral stent insertion for
      any indication by two urologists from January 10, 2015, to October 10, 2016. A
      retrospective chart review was performed of all patients included in the UST
      database. Data extracted included patient demographics, diagnosis, procedure, and
      stent characteristics. RESULTS: A total of 115 patients were included with a mean
      age of 52.4 years; 54% (62/115) were male and 58% (67/115) were Caucasian. This
      cohort represented 146 ureteral stent care plans with 23 patients (23/115; 20%)
      having more than one care plan during the study period. The most common procedure
      performed was ureteroscopy (70/146; 48%) for a diagnosis of nephrolithiasis
      (108/146; 74%). The median indwelling ureteral stent time was 14 days
      (interquartile range: 7-45 days). A total of three patients (3/115; 3%) did not
      return for their scheduled extraction, but were identified only through the
      application. Each patient was contacted, resulting in effective removal of all
      three stents in the office. CONCLUSIONS: Tracking of ureteral stents is critical
      to prevent the patient safety issue of the FUS. The UST is a secure, HIPPA
      compliant, cloud-based application, which once incorporated into the workflow of
      a urologic practice can prevent the FUS.

PMID- 28443679
TI  - Emerging Roles of Carbonyl Sulfide in Chemical Biology: Sulfide Transporter or
      Gasotransmitter?
AB  - SIGNIFICANCE: Carbonyl sulfide (COS) is the most prevalent sulfur-containing gas
      in the Earth's atmosphere, and it plays important roles in the global sulfur
      cycle. COS has been implicated in origin of life peptide ligation, is the primary
      energy source for certain bacteria, and has been detected in mammalian systems.
      Despite this long and intertwined history with terrestrial biology, limited
      attention has focused on potential roles of COS as a biological mediator. Recent
      Advances: Although bacterial COS production is well documented, definitive
      sources of mammalian COS production have not been confirmed. Enzymatic COS
      consumption in mammals, however, is well documented and occurs primarily by
      carbonic anhydrase (CA)-mediated conversion to hydrogen sulfide (H2S). COS has
      been detected in ex vivo mammalian tissue culture, as well as in exhaled breath
      as a potential biomarker for different disease pathologies, including cystic
      fibrosis and organ rejection. Recently, chemical tools for COS delivery have
      emerged and are poised to advance future investigations into the role of COS in
      different biological contexts. CRITICAL ISSUES: Possible roles of COS as an
      important biomolecule, gasotransmitter, or sulfide transport intermediate remain
      to be determined. Key advances in both biological and chemical tools for COS
      research are needed to further investigate these questions. FUTURE DIRECTIONS:
      Further evaluation of the biological roles of COS and disentangling the chemical
      biology of COS from that of H2S are needed to further elucidate these
      interactions. Chemical tools for COS delivery and modulation may provide a first
      avenue of investigative tools to answer many of these questions. Antioxid. Redox
      Signal. 28, 1516-1532.

PMID- 28443682
TI  - Abandonment of Dogs and Cats: Public Opinions as Population Management
      Indicators.
AB  - This study involved characterizing public opinions on selected issues related to
      the abandonment of dogs and cats in Votorantim, Sao Paulo, Brazil. This goal was
      achieved by applying multiple correspondence analysis to answers recorded in
      questionnaires of a population-based survey. The results suggest that the
      tolerance of potentially problematic behaviors did not depend on the specific
      kind of behavior, at least among the behaviors evaluated. The opinions given for
      the most frequent fate of the companion animals did not depend on the species,
      and those who considered abandonment to be one of the most frequent fates tended
      to also consider abandonment as a solution to problematic behaviors. The
      provision of reasons for abandonment was more frequent among interviewees who
      considered abandonment as one of the more common fates of nonhuman animals and as
      a solution to problematic behaviors. Population management interventions should
      be reflected in public opinion, so the public opinion characteristics that were
      found can be used as indicators of changes generated by such interventions.

PMID- 28443684
TI  - Genetic Variants of HIV Type 1 in Men Who Have Sex with Men in Russia.
AB  - The men who have sex with men (MSM) population infected with HIV is poorly
      studied in Russia because of stigma and discrimination. In the first years of the
      HIV epidemic, the only HIV genetic variant that circulated among MSM was subtype
      B, usually acquired abroad. Meanwhile, the massive epidemic of HIV in Russia was
      caused by a highly homogenic subtype A variant, AFSU (A6), and spread mainly
      among drug users. In this study, 155 HIV pol sequences from MSM collected during
      the 2006-2016 period were analyzed. Phylogenetic analysis found that 19.4% of the
      viral sequences from MSM clustered with HIV genetic variants A6 and BFSU, which
      were previously identified only among drug users and their heterosexual partners.
      These data show that the MSM population in Russia is gradually becoming less
      isolated from the general epidemic process. Urgent measures should be taken to
      prevent the spread of HIV among the MSM population.

PMID- 28443686
TI  - Combined clinician-parent delivery of rapid syllable transition (ReST) treatment
      for childhood apraxia of speech.
AB  - PURPOSE: Although speech-language pathologists use parent-delivered home
      practice, little is known about the quality of this practice and its relation to
      treatment efficacy. This study reports both treatment outcomes and fidelity
      following combined clinician-parent delivery of Rapid Syllable Transition (ReST)
      treatment. METHOD: Five children aged 5:1-11:7 with childhood apraxia of speech
      received 12 treatment sessions; six clinic-based and six at home, using multiple
      baselines across participants design. We investigated the children's acquisition
      of treated pseudo words, generalisation to untreated pseudo and real words, and
      maintenance of gains. We also assessed parent and clinician treatment fidelity
      and reliability of perceptual judgements. RESULT: Two children improved on all
      treated behaviours; two showed treatment effect on one of their two treated
      behaviours, and one child had no treatment effect. Only two children generalised
      to the majority of untreated items. Variable treatment fidelity was found across
      parents and aspects of treatment. Child outcome was likely influenced by multiple
      factors, including treatment fidelity, reliability of perceptual judgements and
      child factors. CONCLUSION: Combined clinician-parent delivery of ReST was less
      efficacious than previously reported clinician-only delivered ReST. Further
      investigation of the factors affecting outcome is recommended prior to clinical
      application of the combined model of service delivery.

PMID- 28443685
TI  - Lymphatic Changes in Respiratory Diseases: More than Just Remodeling of the Lung?
AB  - Advances in our ability to identify lymphatic endothelial cells and differentiate
      them from blood endothelial cells have led to important progress in the study of
      lymphatic biology. Over the past decade, preclinical and clinical studies have
      shown that there are changes to the lymphatic vasculature in nearly all lung
      diseases. Efforts to understand the contribution of lymphatics and their growth
      factors to disease initiation, progression, and resolution have led to seminal
      findings establishing critical roles for lymphatics in lung biology spanning from
      the first breath after birth to asthma, tuberculosis, and lung transplantation.
      However, in other diseases, it remains unclear if lymphatics are part of the
      overall lung remodeling process or real contributors to disease pathogenesis. The
      goal of this Translational Review is to highlight some of the advances in our
      understanding of the role(s) of lymphatics in lung disease and shed light on the
      critical needs and unanswered questions that might lead to novel translational
      applications.

PMID- 28443687
TI  - Experiencing menopause in the context of cancer: Women's constructions of
      gendered subjectivities.
AB  - OBJECTIVE: Many women experience premature menopause following cancer treatment,
      accompanied by psychological distress, and poor health-related quality of life.
      In this qualitative study, we examined how women construct their gendered
      subjectivities - their sense of self as a woman - in the context of premature
      menopause after cancer. DESIGN: We analysed data from open-ended survey items and
      semi-structured interviews with women who had experienced cancer. Six hundred and
      ninety-five women completed the online survey and 61 took part in a semi
      structured interview. A thematic decomposition was conducted to identify the
      subject positions associated with menopause taken up by the women. RESULTS: Three
      overall themes were identified: 'The Incomplete Woman,' 'The Abject, Asexual
      Woman' and 'Out of Time and Social Isolation.' Menopause was predominantly
      constructed as a negative experience, similar to older post-menopausal women and
      dissimilar to peers, contributing to experiences of social isolation. Menopause
      also signified the presence of a medically diagnosed cancer condition, and
      uncertainty around cancer prognosis. CONCLUSION: It is important for cancer
      support group leaders and other service providers to be sensitive to women's
      negotiation of menopause following cancer, in the context of broader cultural
      constructions, in order to provide appropriate information and support.

PMID- 28443683
TI  - Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central
      Nervous System.
AB  - SIGNIFICANCE: The thioredoxin (Trx) and glutathione (GSH) systems play important
      roles in maintaining the redox balance in the brain, a tissue that is prone to
      oxidative stress due to its high-energy demand. These two disulfide reductase
      systems are active in various areas of the brain and are considered to be
      critical antioxidant systems in the central nervous system (CNS). Various
      neuronal disorders have been characterized to have imbalanced redox homeostasis.
      Recent Advances: In addition to their detrimental effects, recent studies have
      highlighted that reactive oxygen species/reactive nitrogen species (ROS/RNS) act
      as critical signaling molecules by modifying thiols in proteins. The Trx and GSH
      systems, which reversibly regulate thiol modifications, regulate redox signaling
      involved in various biological events in the CNS. CRITICAL ISSUES: In this
      review, we focus on the following: (i) how ROS/RNS are produced and mediate
      signaling in CNS; (ii) how Trx and GSH systems regulate redox signaling by
      catalyzing reversible thiol modifications; (iii) how dysfunction of the Trx and
      GSH systems causes alterations of cellular redox signaling in human neuronal
      diseases; and (iv) the effects of certain small molecules that target thiol-based
      signaling pathways in the CNS. FUTURE DIRECTIONS: Further study on the roles of
      thiol-dependent redox systems in the CNS will improve our understanding of the
      pathogenesis of many human neuronal disorders and also help to develop novel
      protective and therapeutic strategies against neuronal diseases. Antioxid. Redox
      Signal. 27, 989-1010.

PMID- 28443688
TI  - Use of C-banding for identifying radiation induced micronuclei.
AB  - Differentiation of micronuclei (MN) caused by ionizing radiation from those
      caused by chemicals is a crucial step for managing treatment of individuals
      exposed to radiation. MN in binucleated lymphocytes in peripheral blood are
      widely used as biomarkers for estimating dose of radiation, but they are not
      specific for ionizing radiation. MN induced by ionizing radiation originate
      predominantly as a result of chromosome breaks (clastogenic action), whereas MN
      caused by chemical agents are derived from the loss of entire chromosomes
      (aneugenic action). C-banding highlights centromeres, which might make it
      possible to distinguish radiation induced MN, i.e., as a byproduct of acentric
      fragments, from those caused by the loss of entire chromosomes. To test the use
      of C-banding for identifying radiation induced MN, a blood sample from a healthy
      donor was irradiated with 3 Gy of Co-60 gamma rays and cultured. Cells were
      harvested and dropped onto slides, divided into a group stained directly with
      Giemsa and another processed for C banding, then stained with Giemsa. The
      frequency of MN in 500 binucleated cells was scored for each method. In
      preparations stained with Giemsa directly, the MN appeared as uniformly stained
      structures, whereas after C banding, some MN exhibited darker regions
      corresponding to centromeres that indicated that they were not derived from
      acentric fragments. The C-banding technique enables differentiation of MN from
      acentric chromosomal material. This distinction is useful for improving the
      specificity of the MN assay as a biomarker for ionizing radiation.

PMID- 28443689
TI  - Recent achievements in Tc-99m radiopharmaceutical direct production by medical
      cyclotrons.
AB  - 99mTc is the most commonly used radionuclide in the field of diagnostic imaging,
      a noninvasive method intended to diagnose a disease, assess the disease state and
      monitor the effects of treatments. Annually, the use of 99mTc, covers about 85%
      of nuclear medicine applications. This isotope releases gamma rays at about the
      same wavelength as conventional X-ray diagnostic equipment, and owing to its
      short half-life (t1/2 = 6 h) is ideal for diagnostic nuclear imaging. A patient
      can be injected with a small amount of 99mTc and within 24 h almost 94% of the
      injected radionuclide would have decayed and left the body, limiting the
      patient's radiation exposure. 99mTc is usually supplied to hospitals through a
      99Mo/99mTc radionuclide generator system where it is produced from the beta decay
      of the parent nuclide 99Mo (t1/2 = 66 h), which is produced in nuclear reactors
      via neutron fission. Recently, the interruption of the global supply chain of
      reactor-produced 99Mo, has forced the scientific community to investigate
      alternative production routes for 99mTc. One solution was to consider cyclotron
      based methods as potential replacement of reactor-based technology and the
      nuclear reaction 100Mo(p,2n)99mTc emerged as the most worthwhile approach. This
      review reports some achievements about 99mTc produced by medical cyclotrons. In
      particular, the available technologies for target design, the most efficient
      extraction and separation procedure developed for the purification of 99mTc from
      the irradiated targets, the preparation of high purity 99mTc radiopharmaceuticals
      and the first clinical studies carried out with cyclotron produced 99mTc are
      described.

PMID- 28443691
TI  - Correction to: Krithika, Jyothi, Prasantha, and Ramtej, Mechanism of protective
      effect of phyllanthin against carbon tetrachloride-induced hepatotoxicity and
      experimental liver fibrosis in mice.

PMID- 28443690
TI  - Vitrified-warmed blastocyst transfer on the 5th or 7th day of progesterone
      supplementation in an artificial cycle: a randomised controlled trial.
AB  - Prospective studies comparing different durations of progesterone supplementation
      before transfer of vitrified-warmed blastocysts in an artificial cycle are
      lacking. However, in oocyte donation programmes, the sporadic available evidence
      demonstrates considerable differences in clinical pregnancy rates according to
      the duration of progesterone administration. This randomised controlled trial
      (RCT), included 303 patients undergoing a frozen-thawed embryo transfer (FET) of
      one or two vitrified-warmed blastocyst(s) in an artificial cycle. Randomisation
      was performed when the endometrial thickness reached >=7 mm after oestrogen
      supplementation. One hundred and fifty two patients in group A received 7 d of
      vaginal micronised progesterone tablets and 151 patients in group B received 5 d
      of micronised vaginal progesterone before FET. No differences were seen in
      clinical pregnancy rate between both groups: 42/152 (27.6%) in group A versus
      49/151 (32.5%) in group B. Although no statistically significant difference was
      observed in clinical pregnancy rates, our study was powered to detect an absolute
      difference of 16%. In this regard, we cannot exclude that smaller, clinically
      relevant differences might exist and our study did not have the power to detect
      this. Patients were also not blinded for the intervention, causing a potential
      bias.

PMID- 28443692
TI  - Code of Professional Conduct for Clinical Embryologists.
AB  - The Association of Clinical Embryologists (ACE) is the professional body of and
      for clinical embryologists practising in the UK. ACE was founded in 1993 to
      promote high standards of practice in clinical embryology and to support the
      professional interests of embryologists. ACE presently has in excess of 400
      members.

PMID- 28443693
TI  - Confounder factors masking a Leydig-cell ovarian tumor in a post-menopausal woman
      treated for androgen-positive receptor breast cancer.
AB  - Post-menopause hyperandrogenism is a condition that needs careful evaluation.
      Aromatase inhibitors (AI), which are important in the management of positive
      estrogen breast cancer, and chronic kidney disease (CKD) can puzzle the
      evaluation of this condition. A postmenopause female with type-2 diabetes and
      advanced CKD was attended due to progressive virilization, which has started
      after the introduction of an AI for breast cancer 5 years earlier. Clinical and
      radiological investigation has confirmed a pure Leydig cell tumor as source of
      hyperandrogenism. Re-evaluation of the breast tumor immunohistochemistry has
      shown positive androgen receptor expression and negative expression for estrogen,
      progesterone and HER-2 receptors. Even though an ovarian tumor was the source of
      androgen excess, we discuss that AI could exert a slight contribution to
      patient's virilization by reducing estradiol counterbalance. Also, although the
      onset of hyperandrogenic symptoms was unclear, we could not exclude that the
      ovarian tumor had produced enough androgens to play a role in breast tumor
      progression. This case report supports the literature regarding the possible
      association between Leydig cell tumor and androgen-receptor-positive breast
      cancer development. Finally, progressive hyperandrogenic symptoms in
      postmenopause, even under AI therapy or the presence of advanced CKD, impose a
      more detailed investigation.

PMID- 28443694
TI  - Fractal Features and Surface Micromorphology of Unworn Surfaces of Rigid Gas
      Permeable Contact Lenses.
AB  - PURPOSE: The aim of this exploratory study was to investigate the micromorphology
      of surfaces of rigid gas permeable (RGP) contact lenses (CLs) using atomic force
      microscopy (AFM) followed by fractal analysis. MATERIALS AND METHODS: In order to
      characterize in a quantitative manner the micromorphology of surfaces of new and
      unworn RGP CLs made of twelve different materials, AFM was taken and then
      analyzed using fractal methods. Surface topography was sampled in an intermittent
      contact mode in air, on square areas of 5 * 5 um2 (MultiMode with Nanoscope V
      (Bruker). Spatial characteristics of 3-D surface texture were obtained using
      parameters defined in ISO 25178-2: 2012 norm. RESULTS: The surface texture turned
      out to have complex 3-D nanoscale geometry. For quantitative characterization of
      the properties of surface geometry at nanometer level of CL on the global scale,
      a series of fractal parameters was used. CONCLUSIONS: Statistical and fractal
      parameters of 3-D surfaces can be used by manufacturers to assess the
      micromorphology of CLs in order to improve their 3-D surface texture
      characteristics. These parameters can also be used in an elastic-plastic finite
      element model with contact elements to simulate the friction, wear and micro
      elastohydrodynamic lubrication at a nanometer scale between the CL with the
      corneal surface.

PMID- 28443695
TI  - Safety pharmacology of acute MDMA administration in healthy subjects.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is being investigated in MDMA
      assisted psychotherapy. The present study characterized the safety pharmacology
      of single-dose administrations of MDMA (75 or 125 mg) using data from nine double
      blind, placebo-controlled, crossover studies performed in the same laboratory in
      a total of 166 healthy subjects. The duration of the subjective effects was 4.2
      +/- 1.3 h (range: 1.4-8.2 h). The 125 mg dose of MDMA produced greater 'good drug
      effect' ratings than 75 mg. MDMA produced moderate and transient 'bad drug
      effect' ratings, which were greater in women than in men. MDMA increased systolic
      blood pressure to >160 mmHg, heart rate >100 beats/min, and body temperature >38
      degrees C in 33%, 29% and 19% of the subjects, respectively. These proportions of
      subjects with hypertension (>160 mmHg), tachycardia, and body temperature >38
      degrees C were all significantly greater after 125 mg MDMA compared with the 75
      mg dose. Acute and subacute adverse effects of MDMA as assessed by the List of
      Complaints were dose-dependent and more frequent in females. MDMA did not affect
      liver or kidney function at EOS 29 +/- 22 days after use. No serious adverse
      events occurred. In conclusion, MDMA produced predominantly acute positive
      subjective drug effects. Bad subjective drug effects and other adverse effects
      were significantly more common in women. MDMA administration was overall safe in
      physically and psychiatrically healthy subjects and in a medical setting.
      However, the risks of MDMA are likely higher in patients with cardiovascular
      disease and remain to be investigated in patients with psychiatric disorders.

PMID- 28443698
TI  - Impact of maternal nutritional supplementation in conjunction with a
      breastfeeding support program on breastfeeding performance, birth, and growth
      outcomes in a Vietnamese population.
AB  - PURPOSE: This study aimed to evaluate the effects of maternal nutritional
      supplementation (MNS) in conjunction with a breastfeeding support program on
      birth outcomes and breastfeeding performance. METHODS: A total of 228 singleton
      Vietnamese mothers aged 20-35 years at 26-29 weeks of gestation with pre
      pregnancy body mass index (BMI) < 25.0 kg/m2 were randomized to the intervention
      (n = 114), receiving MNS (252 kcal/day) daily up to 12 weeks postpartum and four
      breastfeeding education and support sessions or to the control (n = 114),
      receiving standards of care. RESULTS: The intervention was 2.09 times more likely
      to exclusively breastfeed over the 12 weeks than the control (95%CI: 1.05-4.13, p
      = .0358), after controlling for potential confounders. Infant's breast milk
      intake was significantly higher in the intervention than the control among
      mothers with baseline mid-upper arm circumference (MUAC) < 50th (p = .0251).
      Infants in the intervention had significantly higher birth weight (p = .0312),
      birth weight-for-age (p = .0141) and birth head circumference-for-age (p =
      .0487), and higher head circumference-for-age z-score (p = .0183) development
      over the postnatal period, compared with the control. CONCLUSIONS: Use of MNS and
      breastfeeding support improve birth outcomes and exclusive breastfeeding (EBF)
      rate in Vietnamese mothers. Additionally, it promotes breast milk production
      among mothers with lower baseline MUAC.

PMID- 28443697
TI  - The cytokine-hormone axis - the link between premenstrual syndrome and postpartum
      depression.
AB  - Premenstrual syndrome (PMS) and related disorders, and postpartum depression
      (PPD) can affect women to the extent that their quality of life and that of their
      near ones can be severely impaired. This review focuses on the different theories
      regarding the etiologies of PMS and PPD, and attempts to draw a link between the
      two. Theories focus mainly on hormonal and cytokine factors throughout different
      phases in the female reproductive cycle. Changes in this symptomatology during
      pregnancy are also reviewed, as are changes in hormones and cytokine levels.
      Hypotheses are thus developed as to why the symptoms experienced in PMS often
      subside during pregnancy yet may recur and be exacerbated after birth, giving
      rise to the symptoms experienced in PPD.

PMID- 28443699
TI  - The Experiences of Parents of Pediatric Patients With Acute Lymphoblastic
      Leukemia, 2 Months After Completion of Treatment.
AB  - Diagnosis and treatment of childhood acute lymphoblastic leukemia (ALL) can be a
      highly stressful time for the entire family. While completion of treatment may
      bring relief to some families, it may also bring about additional anxieties and
      fear. The primary objective of this article is to present an analysis of the
      experiences, emotional states, and support needs of parents of pediatric cancer
      patients 2 months after treatment completion for ALL. Using a qualitative
      interpretive description approach, transcripts from interviews with 17 parents
      from the leukemia/lymphoma program of a large urban pediatric cancer center were
      analyzed using N-Vivo 10 data analysis software. Parents reported simultaneous
      feelings of relief and apprehension, changing relationships with their health
      care team and the experience of returning to a life following treatment. Results
      highlight the need for support for parents on completion of treatment.

PMID- 28443700
TI  - Role of everolimus in the treatment of metastatic HER2-negative/HR-positive
      breast cancer.
AB  - Metastatic breast cancer (mBC) is a leading cause of mortality for women around
      the world. The response to hormonotherapy of the patients with HER2-negative/HR
      positive mBC is usually limited, and many strategies are in place to contrast the
      hormonotherapy resistance. Since efficacy and effectiveness of everolimus have
      been established by many trials, this review is aimed to give a structured
      synthesis to define the everolimus clinical role among the treatment options for
      mBC. Key aspects of everolimus dosing and safety profile, drawn up by relevant
      findings, are included, as well as the role of biomarkers to identify subgroups
      of mBC patients who may best benefit from everolimus treatment.

PMID- 28443696
TI  - The development and modelling of devices and paradigms for transcranial magnetic
      stimulation.
AB  - Magnetic stimulation is a non-invasive neurostimulation technique that can evoke
      action potentials and modulate neural circuits through induced electric fields.
      Biophysical models of magnetic stimulation have become a major driver for
      technological developments and the understanding of the mechanisms of magnetic
      neurostimulation and neuromodulation. Major technological developments involve
      stimulation coils with different spatial characteristics and pulse sources to
      control the pulse waveform. While early technological developments were the
      result of manual design and invention processes, there is a trend in both
      stimulation coil and pulse source design to mathematically optimize parameters
      with the help of computational models. To date, macroscopically highly realistic
      spatial models of the brain, as well as peripheral targets, and user-friendly
      software packages enable researchers and practitioners to simulate the treatment
      specific and induced electric field distribution in the brains of individual
      subjects and patients. Neuron models further introduce the microscopic level of
      neural activation to understand the influence of activation dynamics in response
      to different pulse shapes. A number of models that were designed for online
      calibration to extract otherwise covert information and biomarkers from the
      neural system recently form a third branch of modelling.

PMID- 28443702
TI  - Turmeric Supplementation Improves Serum Glucose Indices and Leptin Levels in
      Patients with Nonalcoholic Fatty Liver Diseases.
AB  - OBJECTIVE: Insulin and leptin resistance are important risk factors for non
      alcoholic fatty liver disease (NAFLD). There is limited evidence regarding the
      effects of turmeric on NAFLD. The aim of this study was to investigate the
      effects of turmeric supplementation on glycemic status and serum leptin levels in
      patients with NAFLD. METHODS: This double-blind randomized controlled clinical
      trial was conducted on 46 patients with NAFLD (21males and 25 females) aged 20-60
      years old and body mass index (BMI) between 24.9 and 40 kg/m2. The turmeric group
      (n = 23) was given six turmeric capsules daily for 12 weeks. Each capsule
      contained 500 mg turmeric powder (6*500 mg). The placebo group (n = 23) was given
      six placebo capsules daily for the same period. Fasting blood samples,
      anthropometric measurements, and physical activity levels were collected at the
      baseline and at the end of the study. Daily dietary intakes also were obtained
      throughout the study. Data were analyzed by independent t test, paired t test and
      analysis of covariance. RESULTS: Turmeric consumption decreased serum levels of
      glucose, insulin, HOMA-IR and leptin (by 1.22, 17.69, 19.48 and 21.33%
      respectively, p < 0.05 for all) over 12 weeks compared with those variables in
      the placebo group. Changes in weight, BMI and liver enzymes were not significant
      compared to the placebo group. CONCLUSIONS: Turmeric supplementation improved
      glucose indexes and serum leptin levels and may be useful in the control of NAFLD
      complications.

PMID- 28443701
TI  - Evaluation of Dietary Intake, Leisure-Time Physical Activity, and Metabolic
      Profile in Women with Mutation in the LMNA Gene.
AB  - INTRODUCTION: Familial partial lipodystrophy (FPL) is a rare genetic disorder
      characterized by selective lack of subcutaneous fat, which is associated with
      insulin-resistant diabetes. The Dunnigan variety (FPLD2) is caused by several
      missense mutations in the lamin A/C (LMNA) gene, most of which are typically
      located in exon 8 at the codon position 482. OBJECTIVE: The aim of this study was
      to assess and compare the dietary intake, leisure-time physical activity (LTPA),
      and biochemical measurements (glucose, A1C, and plasma lipids) in women with
      FPLD2 and without (control group, CG) and to examine the associations between
      dietary intake and biochemical measurements (BM). METHODS: LTPA was measured with
      a questionnaire and metabolic equivalent (MET) hours per week (hours/week) were
      calculated. Dietary intake by the 3-day recall method and clinical laboratory
      parameters were collected. RESULTS: Characteristics of women with FPLD2: 35.8 +/-
      13.9 years, fat mass = 10 +/- 2.3 kg and fat free mass = 41.4 +/- 4.5 kg (p <
      0.05). Women with FPLD2 showed a smaller intake of energy (kcal), lipids, and
      carbohydrates and a large intake of protein (p < 0.01) compared to CG. Comparing
      the 2 groups in terms of LTPA, 78% of women with FPLD2 performed insufficient
      physical activity. In addition, they had a higher levels of glucose, A1C, and
      triglycerides (TG) and lower levels of high-density lipoprotein (HDL). There was
      no correlation between dietary intake and biochemical measurements. CONCLUSIONS:
      Women with FPLD2 have a lower intake of energy (kcal), lipids, and carbohydrates
      and greater changes in biochemical measurements. Because this is a rare disease,
      future studies are needed with encouragement of the practice of physical activity
      and of healthy eating habits, preventing the onset of diseases.

PMID- 28443703
TI  - Psychedelics, Personality and Political Perspectives.
AB  - The psychedelic experience (including psychedelic-induced ego dissolution) can
      effect lasting change in a person's attitudes and beliefs. Here, we aimed to
      investigate the association between naturalistic psychedelic use and personality,
      political perspectives, and nature relatedness using an anonymous internet
      survey. Participants (N = 893) provided information about their naturalistic
      psychedelic, cocaine, and alcohol use, and answered questions relating to
      personality traits of openness and conscientiousness (Ten-Item Personality
      Inventory), nature relatedness (Nature-Relatedness Scale), and political
      attitudes (one-item liberalism-conservatism measure and five-item libertarian
      authoritarian measure). Participants also rated the degree of ego dissolution
      experienced during their "most intense" recalled psychedelic experience (Ego
      Dissolution Inventory). Multivariate linear regression analysis indicated that
      lifetime psychedelic use (but not lifetime cocaine use or weekly alcohol
      consumption) positively predicted liberal political views, openness and nature
      relatedness, and negatively predicted authoritarian political views, after
      accounting for potential confounding variables. Ego dissolution experienced
      during a participant's "most intense" psychedelic experience positively predicted
      liberal political views, openness and nature relatedness, and negatively
      predicted authoritarian political views. Further work is needed to investigate
      the nature of the relationship between the peak psychedelic experience and
      openness to new experiences, egalitarian political views, and concern for the
      environment.

PMID- 28443704
TI  - Independent Variables Affecting Outcome of Carpal Tunnel Release Surgery.
AB  - BACKGROUND: In making the decision to undergo carpal tunnel release (CTR),
      patients may consider probability of symptom resolution. Prior studies have
      examined potential preoperative variables that might influence the postoperative
      outcome. Few studies, however, contain the sample size, prospective design, and
      high participant completion rate to provide solid data from which to counsel
      patients. The purpose of this study was to prospectively evaluate factors that
      have been implicated or dismissed in past studies as sources of outcome variation
      following CTR surgery and provide patient-relatable facts that the surgeon might
      use in preoperative patient counseling. METHODS: One thousand thirty-one
      consecutive patients undergoing open CTR were prospectively enrolled.
      Preoperative frequency of daytime numbness, nighttime awakening, and duration of
      symptoms were recorded in addition to physical exam, height, weight, gender,
      history of diabetes, history of thyroid disease, and severity of
      electrodiagnostic findings. After surgery, patients reported percent resolution
      of numbness at defined intervals. RESULTS: Age and gender are the only
      independent factors that predict the degree of resolution of numbness 6 months
      following surgery. All other studied variables are not independent factors nor
      are any paired combinations of factors. Below the age of 50, the average reported
      resolution of daytime numbness by 6 months is 97.3% (men 91.8% and women 99.4%).
      After age 50, there is a linear 0.77% decline in average resolution of daytime
      numbness per year. CONCLUSIONS: Age and gender but no other studied factors
      predict resolution of daytime numbness in a multivariate model of patients
      undergoing CTR.

PMID- 28443705
TI  - Severity of Withdrawal Symptoms, Plasma Oxytocin Levels, and Treatment Outcome in
      Heroin Users Undergoing Acute Withdrawal.
AB  - Pre-clinical studies show that, following chronic opioid exposure, oxytocin
      neurons exhibit over-excitation upon withdrawal, causing an increase in oxytocin
      brain and plasma levels. Relevant clinical data on humans are scarce. This study
      investigates the opioid withdrawal stress effect on oxytocin plasma levels in
      humans. We evaluated 57 male chronic heroin users in a residential detoxification
      program. We determined plasma oxytocin levels by ELISA and measured the stress
      effects of withdrawal using the COWS scale for opioid withdrawal, the VAS scale
      for craving, and the Hamilton scales for anxiety and depression on the second day
      of admission. Out of the 57 patients enrolled in the study, 27 completed the 21
      day program, while the remaining 30 dropped out prior to completion. Plasma
      oxytocin levels were significantly higher in those individuals who dropped out
      than in those who completed the program. Participants who dropped out at some
      stage scored higher in the COWS, VAS-Craving, and Hamilton-anxiety scales,
      indicating a higher stress and explaining the higher oxytocin levels. In
      addition, plasma oxytocin levels correlated positively with the scores achieved
      in the COWS and Hamilton-anxiety scales. Higher withdrawal stress levels are
      associated with higher plasma oxytocin levels and early treatment discharge.

PMID- 28443706
TI  - ?

PMID- 28443707
TI  - ?

PMID- 28443709
TI  - ?

PMID- 28443708
TI  - ?

PMID- 28443710
TI  - ?

PMID- 28443711
TI  - ?

PMID- 28443712
TI  - ?

PMID- 28443713
TI  - ?

PMID- 28443714
TI  - ?

PMID- 28443715
TI  - ?

PMID- 28443716
TI  - ?

PMID- 28443717
TI  - ?

PMID- 28443718
TI  - Crosstalk Between Bone and Fat Tissue: Associations Between Vitamin D,
      Osteocalcin, Adipokines, and Markers of Glucose Metabolism Among Adolescents.
AB  - OBJECTIVES: This study aimed to investigate the relationship between 25
      hydroxyvitamin D (25(OH)D), osteocalcin, markers of glucose metabolism, and
      obesity-related parameters among adolescents. METHODS: This was a cross-sectional
      study with 198 adolescents age 14-18 years. Weight, height, and waist and hip
      circumferences were measured, as well as the following biochemical parameters:
      serum 25(OH)D, parathyroid hormone (PTH), total (tOC) and undercarboxylated
      (ucOC) osteocalcin, adiponectin, leptin, glucose, and insulin. The homeostasis
      model of assessment estimate of insulin resistance (HOMA-IR) and beta-cell
      function (HOMA-beta) and quantitative insulin sensitivity check index (QUICKI)
      were calculated. Student's t test, analysis of variance (ANOVA), Pearson's
      correlation, and linear regression models were performed. RESULTS: Overweight was
      observed in 42.6% of the sample. This group presented significantly higher PTH,
      leptin, insulin, HOMA-IR, and HOMA-beta and lower 25(OH)D, adiponectin, tOC,
      ucOC, and QUICKI than normal-weight subjects. 25(OH)D was positively correlated
      with ucOC and adiponectin and negatively associated with body mass index (BMI),
      weight, and waist circumference (p < 0.05 for all). The association between
      25(OH)D and ucOC was also observed in the multiple regression analysis, adjusted
      for age, BMI, and season of the year (partial r2 = 0.071, p < 0.0001). 25(OH)D
      and ucOC were not associated with markers of glucose metabolism. However, leptin
      was strongly correlated with insulin, HOMA-IR, HOMA-beta, and QUICKI (p < 0.0001
      for all). CONCLUSION: The present study demonstrated that undercarboxylated
      osteocalcin is related to 25(OH)D and adiponectin concentrations. Both ucOC and
      25(OH)D were lower in overweight and obese adolescents, reinforcing the
      importance of fighting obesity. Although a relationship of ucOC and 25(OH)D with
      markers of glucose metabolism was not observed, leptin has shown to be the
      hormone most related to energy homeostasis.

PMID- 28443719
TI  - Influence of quartz exposure on lung cancer types in cases of lymph node-only
      silicosis and lung silicosis in German uranium miners.
AB  - Inhaled crystalline quartz is a carcinogen. Analyses show differences in the
      distribution of lung cancer types depending on the status of silicosis. Using
      2,524 lung tumor cases from the WISMUT autopsy repository database, silicosis was
      differentiated into cases without silicosis in lung parenchyma and its lymph
      nodes, with lymph node-only silicosis, or with lung silicosis including lymph
      node silicosis. The proportions of adenocarcinoma, squamous cell carcinoma, and
      small-cell lung carcinoma mortality for increasing quartz exposures were
      estimated in a multinomial logistic regression model. The relative proportions of
      the lung cancer subtypes in lymph node-only silicosis were more similar to lung
      silicosis than without any silicosis. The results support the hypothesis that
      quartz-related carcinogenesis in case of lymph node-only silicosis is more
      similar to that in lung silicosis than in without silicosis.

PMID- 28443720
TI  - Modulatory Effects of a Nutraceutical Supplement on Saos-2 Cells Reveal Its
      Phlebotonic Activity.
AB  - OBJECTIVE: Herbal extract compositions are largely used to manage vein diseases.
      We prepared a new composition of herbs, named FLEBO OKTM, that, when administered
      as a nutraceutical to patients affected by peripheral vascular diseases, was able
      to improve their health conditions. We analyzed the effects of this nutraceutical
      composition on in vitro cultured cells with the aim to obtain information about
      its mechanisms of action. METHODS: A culture of human osteoblast cell line Saos-2
      was stimulated with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta
      to induce the expression of some chemokines and matrix metalloproteases (MMPs).
      This cell culture was then exposed to the prepared composition and the amount of
      expression of the genes coding for the monocyte chemotactic protein (MCP)-1, IL
      8, IL-1beta, MMP-2, MMP-3, MMP-9 proteins was measured by real-time polymerase
      chain reaction (RT-PCR). The experiments were repeated exposing the cells to the
      same amount of the well-known micronized purified flavonoid fraction. Moreover,
      we describe the effects of the administration of nutraceutical composition to 20
      patients affected by peripheral vascular diseases and 20 healthy individuals.
      RESULTS: The RT-PCR analyses showed that the new composition induces the
      expression of MMP-3 and MMP-9 and downregulates MMP-2 in cell cultures stimulated
      with IL-1beta, whereas it induces the expression of IL-8 and represses the
      expression of IL-1beta and MCP-1 in cell cultures stimulated with TNF-alpha. The
      induction of the expression of MMP-3 and the downregulation of MCP-1 might result
      in an antiplatelet activity that was not observed for the micronized purified
      flavonoid fraction. Interviewed patients reported an improvement in their
      conditions after 1 month of FLEBO OK treatment. CONCLUSION: These findings could
      provide a hypothesis for the high efficiency of the identified nutraceutical
      composition to management of peripheral vascular diseases.

PMID- 28443721
TI  - Evaluation of Surgical Outcomes with Photoselective GreenLight XPS Laser
      Vaporization of the Prostate in High Medical Risk Men with Benign Prostatic
      Enlargement: A Multicenter Study.
AB  - OBJECTIVE: To evaluate the safety and short-term outcomes of photoselective
      vaporization of the prostate (PVP) using GreenLight XPSTM in treatment of high
      medical risk (HMR) men. METHODS: A multicenter retrospective analysis of 941 men
      who underwent PVP between August 2010 and August 2014 was performed. Patients
      were considered HMR if they had an American Society of Anesthesiologists physical
      status score >=3. Postoperative adverse events, unexpected postoperative medical
      provider visits after intervention, and functional urinary outcomes were
      examined. RESULTS: HMR men (n = 273) were older (mean age 72.3 +/- 8.1 years vs
      67.1 +/- 9 years, p <= 0.01), had larger prostate volumes (82.8 +/- 48.2 g vs
      73.7 +/- 49.4 g, p < 0.01), and were more likely to be on anticoagulant and
      antiplatelet medications (all p <= 0.01). Moreover, overall operative time (65 +/
      35.1 minutes vs 53.9 +/- 24.9 minutes), energy delivered (313.4 +/- 207 kJ vs
      258 +/- 164 kJ), and energy density used (4.2 +/- 3.8 kJ/g vs 3.8 +/- 3 kJ/g)
      were greater in the HMR group (all p <= 0.05). Although HMR men were more often
      treated in a hospital setting (p <= 0.01), there were no differences in
      intraoperative adverse events. At 6 months, both groups had notable improvements
      from baseline for International Prostate Symptom Score, quality of life due to
      urinary symptoms, maximum urinary flow rate, postvoid residual urine volume, and
      prostate-specific antigen. Regarding safety, the two groups had comparable 90-day
      Clavien-Dindo complication rates, numbers of urgent care visits, and numbers of
      outpatient consultations. HMR men, however, had more hospital readmissions within
      90 days postsurgery (3.7% vs 1.3%; p = 0.04). CONCLUSIONS: Despite older age,
      greater comorbidity, and significant use of anticoagulants, HMR men who undergo
      photoselective vaporization benefit from symptom improvement and show no clinical
      difference in adverse event profiles. GreenLight-XPS produces similar short-term
      outcomes in patients with significant comorbidities when compared with healthy
      patients.

PMID- 28443723
TI  - Glucuronidation of icaritin by human liver microsomes, human intestine microsomes
      and expressed UDP-glucuronosyltransferase enzymes: identification of UGT1A3, 1A9
      and 2B7 as the main contributing enzymes.
AB  - 1. Icaritin is a natural flavonoid with anti-osteoporosis activity. This study
      aimed to characterize icaritin glucuronidation by pooled human liver microsomes
      (HLM) and pooled human intestine microsomes (HIM), and to determine the
      contribution of individual UDP-glucuronosyltrans-ferase (UGT) enzyme to icaritin
      glucuronidation. 2. Glucuronidation rates were determined by incubating icaritin
      with uridine diphosphate glucuronic acid (UDPGA)-supplemented microsomes. Kinetic
      parameters were derived by appropriate model fitting. Relative activity factors
      and activity correlation analysis were performed to identify main UGT isoforms.
      3. UGT1A3, 1A7, 1A8, 1A9 and 2B7 were mainly responsible for catalyzing the
      formation of two glucuronides (G1 and G2). Icaritin 3-O-glucuronidation (G1) was
      significantly correlated with Chenodeoxycholic acid (CDCA) glucuronidation (r =
      0.787, p = 0.002), propofol glucuronidation (r = 0.661, p = 0.019) and Zidovudine
      (AZT) glucuronidation (r = 0.805, p = 0.002). Similarly, icaritin 7-O
      glucuronidation (G2) was also correlated with CDCA glucuronidation (r = 0.640, p
      = 0.025), propofol glucuronidation (r = 0.592, p = 0.043) and AZT glucuronidation
      (r = 0.661, p = 0.019). In addition, UGT1A3, 1A9 and 2B7 contributed 37.5, 33.8
      and 21.3% for G1 in pooled HLM, respectively. Also, UGT1A3, 1A9 and 2B7
      contributed 34.3, 20.0 and 8.6% for G2 in pooled HLM, respectively. 4. Icaritin
      was subjected to significant glucuronidation, wherein UGT1A3, 1A7, 1A8, 1A9 and
      2B7 were main contributing enzymes.

PMID- 28443722
TI  - Reflections on O2 as a Biosignature in Exoplanetary Atmospheres.
AB  - Oxygenic photosynthesis is Earth's dominant metabolism, having evolved to harvest
      the largest expected energy source at the surface of most terrestrial habitable
      zone planets. Using CO2 and H2O-molecules that are expected to be abundant and
      widespread on habitable terrestrial planets-oxygenic photosynthesis is plausible
      as a significant planetary process with a global impact. Photosynthetic O2 has
      long been considered particularly robust as a sign of life on a habitable
      exoplanet, due to the lack of known "false positives"-geological or photochemical
      processes that could also produce large quantities of stable O2. O2 has other
      advantages as a biosignature, including its high abundance and uniform
      distribution throughout the atmospheric column and its distinct, strong
      absorption in the visible and near-infrared. However, recent modeling work has
      shown that false positives for abundant oxygen or ozone could be produced by
      abiotic mechanisms, including photochemistry and atmospheric escape.
      Environmental factors for abiotic O2 have been identified and will improve our
      ability to choose optimal targets and measurements to guard against false
      positives. Most of these false-positive mechanisms are dependent on properties of
      the host star and are often strongest for planets orbiting M dwarfs. In
      particular, selecting planets found within the conservative habitable zone and
      those orbiting host stars more massive than 0.4 M? (M3V and earlier) may help
      avoid planets with abundant abiotic O2 generated by water loss. Searching for O4
      or CO in the planetary spectrum, or the lack of H2O or CH4, could help
      discriminate between abiotic and biological sources of O2 or O3. In advance of
      the next generation of telescopes, thorough evaluation of potential biosignatures
      including likely environmental context and factors that could produce false
      positives-ultimately works to increase our confidence in life detection. Key
      Words: Biosignatures-Exoplanets-Oxygen-Photosynthesis-Planetary spectra.
      Astrobiology 17, 1022-1052.

PMID- 28443724
TI  - Genetic Diversity of HIV-1 Gene vif Among Treatment-Naive Brazilians.
AB  - HIV-1 has the Vif protein, which binds to human antiviral proteins APOBEC3 to
      form complexes to be degraded by cellular proteolysis. To further explore HIV-1
      diversity at the population level, we analyzed blood samples from 317 treatment
      naive patients in Brazil. In this study, we explored the correlations of Vif
      polymorphisms with clinical parameters of the patients and found that mutation
      K22H is associated with low CD4+ cell counts and higher viral loads. Phylogenetic
      analysis of the vif gene indicated that subtype B was predominant in ~77%
      (243/317) of the patients, followed by HIV-1 F ~18% (56/317), and subtype C ~4%
      (12/317); five samples were BF recombinants (~1% of patients), and one was an AG
      recombinant. On the basis of the vif gene, we detected the presence of one AG and
      several previously unknown BF intersubtypes in this population. The global mean
      diversity, measured by pairwise distances, was 0.0931 +/- 0.0006 among sequences
      of subtype B (n = 243), whereas the mean diversity of subtype C sequences (n =
      12) was 0.0493 +/- 0.001 and that of subtype F (n = 56) was 0.050 +/- 0.001.

PMID- 28443733
TI  - Proceedings of the British Neurosurgery Research Group Meeting.

PMID- 28443729
TI  - Proceedings of the 144th Meeting of the Society of British Neurological Surgeons,
      held jointly with the Brazilian Neurosurgical Society.

PMID- 28443750
TI  - Editorial.

PMID- 28443736
TI  - Brain Resting-State Functional Connectivity Is Preserved Under Sevoflurane
      Anesthesia in Patients with Pervasive Developmental Disorders: A Pilot Study.
AB  - Functional connectivity studies play a huge role in understanding the
      relationship between the network connections and the behavioral phenotype of
      patients with pervasive developmental disorders (PDD). Some patients with PDD may
      not be able to tolerate the imaging procedure while they are awake, and, hence,
      they often need general anesthesia. General anesthesia is a confounding factor in
      functional imaging studies due to its effect on the functional connectivity. The
      objective of this study is to look at the resting-state functional connectivity
      (RS-FC) under sevoflurane anesthesia in patients with PDDs. Thirteen adults with
      PDD scheduled for magnetic resonance imaging (MRI) of the brain under general
      anesthesia were recruited for the study. Resting-state functional MRI (fMRI)
      scans were acquired at 1 minimum alveolar concentration (MAC) of sevoflurane.
      Spontaneous blood oxygenation level-dependent fluctuations were measured, and a
      seed-voxel analysis was done to identify the resting-state networks. Subjects'
      data were compared with data from 16 nonanesthetized healthy controls. Six
      networks (default mode network [DMN], executive control network [ECN], salience
      network [SN], auditory, visual, and sensorimotor) were investigated. At 1 MAC
      sevoflurane anesthesia, RS-FC was preserved in all the networks. Secondary
      analysis of connectivity showed a decrease in connectivity within the thalamus
      and an increase in DMN-ECN and DMN-SN cross-network connectivity in the
      anesthetized patient group compared to healthy controls. Previous reports
      suggested that even mild levels of anesthesia could reduce overall fluctuation
      levels in the major brain. However, our results provide strong evidence that most
      networks can sustain detectable levels of activity in patients with PDDs even
      under deep levels of anesthesia.

PMID- 28443751
TI  - A prospective cohort study assessing differences in cosmetic appreciation of
      lateralization while smiling in patients with a peripheral facial palsy.
AB  - We investigated the differences in cosmetic appreciation of patients with a left
      and a right peripheral facial palsy (PFP) while smiling. Smiling pictures of
      patients with a facial palsy with House-Brackmann II-VI were reversed as a mirror
      image and offered as a pair of pictures, together with the true image. Twenty-six
      patients with a PFP and 24 medical professionals familiar with facial palsy were
      asked to choose the most attractive photograph. Patients rated their own
      pictures. Medical professionals preferred pictures of patients with a right and
      left PFP in, respectively, a mean of 43.00 +/- 12.25% and 57.00 +/- 12.28% (p =
      .005). Patients with a right PFP chose their mirror and true image in 65% and 35%
      in smiling pictures (p = .01). Patients with a left PFP facial palsy chose their
      mirror and true image in 58% and 42% in smiling pictures (p = .02). The House
      Brackmann score and age of the patients did not influence preferences of medical
      professionals and patients. We have found that medical professionals have a
      significant preference for pictures of patients with a left PFP. Patients with a
      left PFP and right PFP significantly prefer their mirror image in smiling
      pictures.

PMID- 28443760
TI  - Editor's note.

PMID- 28443752
TI  - Prospective comparison of the efficacy of caudal versus periprostatic nerve
      block, both with intrarectal local anesthesia, during transrectal ultrasonography
      guided prostatic needle biopsy.
AB  - OBJECTIVE: The aim of this study was to compare the effectiveness of caudal block
      (CB) versus periprostatic nerve block (PPNB), both with intrarectal local
      anesthesia (IRLA), in reducing pain during transrectal ultrasonography (TRUS)
      guided prostatic biopsy. MATERIALS AND METHODS: This study included 532 patients:
      266 patients received CB with IRLA and 266 patients PPNB with IRLA. A visual
      analogue scale (VAS) was applied to prospectively evaluate pain (1) at induction
      of anesthesia, (2) at insertion of the TRUS probe, (3) at needle penetration to
      the prostate, and (4) throughout the biopsy procedure. Pain scores were compared
      to evaluate differences between groups. The secondary endpoint of serious
      complication rate was also evaluated. As a subanalysis, the pain scores were
      compared in patients with high body mass index (BMI >=25 kg/m2). RESULTS:
      Overall, the pain score in the PPNB group was significantly lower than in the CB
      group at induction of anesthesia (mean +/- SD: 2.0 +/- 1.9 vs 2.9 +/- 2.1, p =
      .0001) but higher at insertion of the TRUS probe (2.7 +/- 2.5 vs 1.9 +/- 1.7, p =
      .009). The pain score did not differ significantly between groups at needle
      penetration or throughout the biopsy. Univariate analyses indicated no
      significant association between VAS scores and patient demographics. Overall
      rates of serious complications did not differ between the two groups (5.6% vs
      5.3%, p = .85). In patients with high BMI, the pain score was significantly lower
      in the PPNB group than in the CB group throughout the procedure (2.5 +/- 2.0 vs
      3.5 +/- 2.5, p = .03). CONCLUSIONS: Both procedures were equally effective in
      reducing pain, and the incidence of serious complications was similar. PPNB with
      IRLA may be more applicable than CB with IRLA in obese patients.

PMID- 28443762
TI  - Prediction of therapy response in ovarian cancer: Where are we now?
AB  - Therapy resistance is a major challenge in the management of ovarian cancer (OC).
      Advances in detection and new technology validation have led to the emergence of
      biomarkers that can predict responses to available therapies. It is important to
      identify predictive biomarkers to select resistant and sensitive patients in
      order to reduce important toxicities, to reduce costs and to increase survival.
      The discovery of predictive and prognostic biomarkers for monitoring therapy is a
      developing field and provides promising perspectives in the era of personalized
      medicine. This review article will discuss the biology of OC with a focus on
      targetable pathways; current therapies; mechanisms of resistance; predictive
      biomarkers for chemotherapy, antiangiogenic and DNA-targeted therapies, and
      optimal cytoreductive surgery; and the emergence of liquid biopsy using recent
      studies from the Medline database and ClinicalTrials.gov.

PMID- 28443763
TI  - <emph type="2">Intractable Hepatic Encephalopathy After Tips with
      Polytetrafluoroethylene-covered Stent-Graft</emph&gt.

PMID- 28443764
TI  - Effects on Cell Proliferation, Activator Protein-1 and Genotoxicity by Fecal
      Water from Patients with Colorectal Adenomas.
AB  - BACKGROUND: The free water phase of feces (fecal water) may mediate the effects
      of diet on colon carcinogenesis. We examined the effects of fecal water from
      adenoma patients and controls on three parameters in colonocytes believed to be
      relevant to tumorigenesis, i.e. genotoxicity in intact cells and on isolated DNA,
      proliferative activity and activator protein-1 (AP-1) activity. METHODS:
      Genotoxicity in intact colonic cells was assayed using the single-cell gel
      electrophoresis assay ('comet' assay) and on isolated DNA using double-stranded
      DNA from the X-174 RF plasmid. Cell proliferation was assessed using the
      commercially available 'alamar blue' proliferation kit and AP-1 activity using
      cells transiently transfected with an AP-1-luciferase reporter construct.
      RESULTS: The data showed that lipid extracts of fecal water samples from the
      adenoma patients had a significantly higher capacity to induce cell proliferation
      than those from controls, and that this effect could be explained to a large
      extent by the concentrations of deoxycholic and chenodeoxycholic acids in the
      fecal water using regression models. No difference between patients and controls
      was observed for induction of AP-1 activity or induction of DNA strand breaks in
      intact cells. However, induction of DNA strand breaks in isolated DNA was
      significantly higher for the fecal waters from patients than for those from
      controls, which could be explained in part in a regression model by
      concentrations of lithocholic acid in fecal water and fecapentaene-12 in feces.
      CONCLUSIONS: Our results support the hypothesis that the biochemistry of fecal
      waters from adenoma patients and controls differs.

PMID- 28443765
TI  - Association of TNF-alpha-857C with Inflammatory Bowel Disease in the Australian
      Population.
AB  - BACKGROUND: It is now well established that susceptibility to inflammatory bowel
      disease is in part genetic, with one localization on chromosome 6 (IBD3) having
      been replicated in a number of populations. A candidate in that region, TNF
      alpha, contains polymorphisms in the promoter region that appear to be associated
      with disease. METHODS: More than 600 individuals from 170 multiplex IBD families
      were genotyped for four polymorphisms in the TNF-alpha gene and analysed for
      association. RESULTS AND CONCLUSION: A strong association was observed between
      transmission of the -857 C allele and disease. This effect was strongest in those
      families in which the NOD2 risk alleles are also segregating, supporting the
      existence of an interaction between IBD3 and IBD1 on chromosome 16.

PMID- 28443766
TI  - Pioglitazone, a Specific Ligand of the Peroxisome Proliferator-Activated Receptor
      Gamma Reduces Gastric Mucosal Injury Induced by Ischaemia/Reperfusion in Rat.
AB  - BACKGROUND: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a
      ligand-dependent nuclear receptor that has been implicated in the control of
      metabolism and numerous cellular processes, including cell cycle control,
      carcinogenesis, and inflammation. The present study was designed to investigate
      the effect of the specific PPARgamma ligand, pioglitazone, on the mucosal lesions
      induced by ischaemia and reperfusion (I/R) in rats. METHODS: I/R lesions were
      induced in Wistar rats by applying a small clamp to the coeliac artery for 30 min
      (ischaemic phase), followed by the removal of the clamp for 3 h (reperfusion
      phase). Vehicle (saline) or increasing doses of pioglitazone (2.5, 10, and 30
      mg/kg i.g.) were given 30 min before exposure to I/R. The animals were killed
      immediately after the end of the reperfusion phase (time 0) and at 12 and 24 h
      after I/R. The area of gastric lesions was measured by planimetry, and the
      gastric blood flow was determined by the H[Formula: See Text] gas clearance
      method. The gastric mucosal gene expressions of PPARgamma, interleukin-1beta (IL
      1beta), tumour necrosis factor alpha (TNF-alpha), leptin, cyclooxygenase-1 (COX
      1) and cyclooxygenase-2 (COX-2) were examined by RT-PCR. In addition, protein
      expression of COX-2 and leptin was assessed by Western blot. RESULTS: The
      pretreatment with pioglitazone reduced in a dose-dependent manner the mean lesion
      area induced by I/R, and this effect was accompanied by a significant increase in
      the gastric blood flow. The decrease in gastric ulcerations by pioglitazone was
      also observed 12 and 24 h after the I/R. The PPARgamma mRNA was weakly expressed
      in the intact gastric mucosa, but significantly up-regulated after exposure to
      I/R at each time interval studied. The expression of IL-1beta was not changed
      significantly after pioglitazone applied i.g. at doses 2.5 and 10 mg/kg, but it
      was down-regulated at the dose 30 mg/kg. TNFalpha mRNA was strongly increased
      after the exposure to I/R, but it was down-regulated after pioglitazone
      pretreatment. In contrast, both leptin and COX-2 mRNA and protein expression were
      increased in the gastric mucosa after exposure to I/R. The pretreatment with
      pioglitazone caused a significant up-regulation of mRNA and protein expression of
      leptin, reaching its peak at the dose 30 mg/kg i.g. In contrast, COX-2 expression
      did not change significantly after the 2.5 and 10 mg/kg of pioglitazone, but it
      significantly decreased after pioglitazone at dose 30 mg/kg given to rats before
      exposure to I/R. CONCLUSIONS: Pioglitazone reduces the acute erosions and deeper
      gastric lesions induced by I/R. The beneficial effect of this PPARgamma ligand on
      I/R-induced gastric damage may be due to its anti-inflammatory properties,
      especially to the reduction in TNF-alpha expression and to up-regulation of
      leptin mRNA in the gastric mucosa. The inhibition of COX-2 expression by
      pioglitazone may reflect the anti-inflammatory properties of this compound.

PMID- 28443768
TI  - Believe in Iron.

PMID- 28443767
TI  - Comparison of Gastric Histology Among Swedish and Japanese Patients with Peptic
      Ulcer and <emph type="2">Helicobacter pylori</emph> Infection.
AB  - BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between
      different ethnic groups. Gastric histopathology and the occurrence of H. pylori
      organisms in the stomach were investigated in healed duodenal (DU) and gastric
      (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial.
      METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological
      gastritis variables and H. pylori were assessed from biopsy specimens obtained
      using a specific sampling protocol and interpreted according to guidelines of the
      updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be
      very different between the recruited Japanese (39:55) and Swedish (0:109)
      patients. A comparison of data from SDU and JDU showed that the prevalence of H.
      pylori infection and the antral predominant gastritis demonstrated by both SDU
      and JDU were essentially identical. A comparison of data from JDU and JGU
      demonstrated a greater prevalence of H. pylori infection in the antrum, but not
      corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal
      metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all
      patients. CONCLUSIONS: The site specified biopsy methodology and standardized
      interpretation criteria utilized in this study clearly show that the
      histotopographic profile of Swedish and Japanese DU patients is essentially the
      same.

PMID- 28443769
TI  - The C/C_13910 and G/G_22018 Genotypes for Adult-type Hypolactasia are not
      Associated with Inflammatory Bowel Disease.
AB  - BACKGROUND: Lactose intolerance with adult-onset is due to the inadequate
      enzymatic activity of lactase-phlorizin hydrolase (LPH). It is frequently seen in
      patients with Crohn disease, but the mechanism remains to be elucidated. Two DNA
      genotypes, C/C_13910 and G/G_22018, located upstream from the LCT locus, the gene
      encoding for LPH, were recently identified as representing genetic markers for
      lactose intolerance. We utilized these two DNA genotypes to study their role in
      inflammatory bowel disease. METHODS: We investigated the prevalence of these two
      DNA variants using specific restriction enzyme digest assays in 166 patients with
      Crohn disease, in 120 healthy first-degree relatives of Crohn disease patients,
      in 63 patients with ulcerative colitis and in 187 healthy individuals. RESULTS:
      The analysis revealed a frequency of 21.4% of the 2 genotypes for adult-type
      hypolactasia in our studied German cohort of healthy individuals, which is higher
      than previously reported (15%) based on the hydrogen (H2) breath test. This might
      indicate a higher sensitivity of genotyping, but it has to be confirmed in larger
      cohorts. No significant difference was detectable in the frequency of the
      C/C_13910 and G/G_22018 genotypes in patients with Crohn Disease (C/C_13910:
      21.7%; G/G_22018: 22.3%) compared to first-degree relatives (C/C_13910: 21.7%;
      G/G_22018: 20.8%), patients with ulcerative colitis (C/C_13910: 20.3%; G/G_22018:
      20.3%) and healthy individuals (C/C_13910: 21.4%; G/G_22018: 21.4%). CONCLUSIONS:
      The C/C_13910 and G/G_22018 genotype of adult-type hypolactasia is not associated
      with susceptibility to the pathogenesis of Crohn disease and ulcerative colitis.

PMID- 28443770
TI  - Psychological Factors in Irritable Bowel Syndrome: a Population-based Study of
      Patients, Non-patients and Controls.
AB  - BACKGROUND: It has been suggested that psychopathology in irritable bowel
      syndrome (IBS) patients is a function of patient status rather than of the
      disease. Although there are many studies comparing IBS patients, IBS non
      patients, and controls with each other, no previous study has recruited all three
      groups from a representative community sample and had all subjects diagnosed by a
      physician. In the present study we aimed to compare psychological factors in IBS
      patients, IBS non-patients, and normal controls in a sample recruited from the
      population. METHODS: Subjects aged 18-45 years were recruited from a random
      sample of the normal population. Seventeen (2 M and 15 F) IBS patients were
      matched by sex and age with IBS non-patients and normals. Measures of personality
      traits, interpersonal distress, and temporary psychological distress were used. A
      physician diagnosed all 51 subjects in order to exclude possible gastrointestinal
      diagnoses other than IBS. RESULTS: Controls often differed from IBS non-patients
      and patients on the personality, interpersonal, and psychological distress
      measures, while IBS non-patients and patients very rarely differed from each
      other. All three groups were non-alexithymic. CONCLUSIONS: The results indicate
      that there are psychopathological differences between normals and IBS persons
      (patients and non-patients), but they could not confirm that psychopathology was
      a function of patient status. Whether this psychopathology is a vulnerability
      factor for IBS, or a consequence of it, remains to be studied.

PMID- 28443771
TI  - Tumour Necrosis Factor Alpha Antibody Affects Gastrin Release in Crohn Disease.
AB  - BACKGROUND: Gastrin plays an important role in the regulation of gastric acid
      secretion in humans. Tumour necrosis factor alpha (TNF-alpha) stimulates gastrin
      release from antral G cells in vitro. The aim was to determine whether gastrin
      release decreases in patients with Crohn disease treated with monoclonal antibody
      to TNF-alpha. METHODS: Twenty-five consecutive patients with Crohn disease (10 M,
      15 F; 18 with fistulas) were treated with a single intravenous infusion of the
      monoclonal antibody to TNF-alpha, infliximab, at a dose of 5 mg/kg. Basal and
      bombesin stimulated gastrin was measured after an overnight fast immediately
      before and 2 weeks after infliximab. Helicobacter pylori status was determined by
      serology. RESULTS: Twenty-two patients were H. pylori-negative. Basal plasma
      gastrin was 21 (16-26) pmol/L before and 19 (15-25) pmol/L after infliximab (NS).
      Bombesin stimulated gastrin decreased from 49 (40-62) pmol/L before to 36 (33-59)
      pmol/L (P < 0.005) 2 weeks after infliximab. CONCLUSION: Gastrin release in
      response to bombesin decreases in patients with Crohn disease treated with
      infliximab.

PMID- 28443772
TI  - Idiopathic Thrombocytopenic purpura and Helicobacter pylori Infection

PMID- 28443773
TI  - Gastric Carcinoid in a Young Woman with Systemic Lupus Erythematosus and Atrophic
      Autoimmune Gastritis.
AB  - BACKGROUND: Gastric carcinoid is a rare tumour that is associated with chronic
      atrophic gastritis in the majority of cases. It usually occurs in the 6th or 7th
      decade of life and is rarely diagnosed in patients under 30 years of age.
      METHODS: We describe a case of multiple gastric carcinoids in a 23-year-old woman
      with systemic lupus erythematosus and atrophic autoimmune gastritis--an
      association that has not been reported previously. RESULTS: The combination of
      atrophic autoimmune gastritis and gastric carcinoid with other autoimmune
      disorders has rarely been reported in the English medical literature. CONCLUSION:
      The fact that it mostly concerns (relatively) young patients may suggest a
      potential causative relation between those autoimmune disorders and the early
      development of atrophic gastritis with hypergastrinaemia, which subsequently
      leads to the occurrence of gastric carcinoid tumours at a young age.

PMID- 28443775
TI  - Erratum.

PMID- 28443774
TI  - RDP58, a Novel Immunomodulatory Peptide with Anti-Inflammatory Effects. A
      Pharmacological Study in Trinitrobenzene Sulphonic Acid Colitis and Crohn
      Disease.
AB  - BACKGROUND: Tumour necrosis factor (TNF) plays a key role in the pathogenesis of
      Crohn disease (CD). RDP58 is a novel anti-inflammatory decapeptide which was
      developed using a novel rational design strategy. Recently, RDP58 has proved to
      be a potent inhibitor of TNF production at a post-transcriptional step. The aims
      of this study were to investigate the anti-inflammatory properties of RDP58 ex
      vivo in human CD and in vivo in an experimental model colitis. METHODS: Biopsies
      and lamina propria mononuclear cells from inflamed colonic mucosa of 18 CD
      patients were cultured for 24 h in the presence or absence of RDP58. TNF was
      quantified in a bioassay; interferon (IFN)-gamma and interleukin (IL)-1beta
      levels were measured by enzyme-linked immunosorbent assays. Colitis was induced
      by intra-rectal administration of 2, 4, 6 trinitrobenzene sulphonic acid (TNBS)
      in rats. Inflammation was assessed following 7 days of oral therapy with RDP58 or
      vehicle alone. RESULTS: RDP58 led to decreased TNF and IFN-gamma (but not IL
      1beta) production by biopsies and lamina propria mononuclear cells from CD
      patients. In rats with TNBS-induced colitis, oral RDP58 therapy reduced weight
      loss and diarrhoea and improved macroscopic and histological inflammation scores.
      CONCLUSIONS: Our results suggest that RDP58 may be an effective therapy for CD
      with the clinical advantage of an oral administration.

PMID- 28443779
TI  - Proceedings of the 142nd Meeting of the Society of British Neurological Surgeons.

PMID- 28443783
TI  - Risk due to exposure to metallic elements in a birdshot factory.
AB  - The contribution of biological and environmental monitoring to the risk
      assessment of occupational exposure to lead (Pb), arsenic (As), and antimony (Sb)
      was studied in 18 workers at a birdshot factory (Exposed) and in 18 control
      workers (Controls) by the determination of both airborne Pb (PbA) and airborne As
      (AsA) only in the exposed workers and blood Pb (PbB), erythrocytic zinc
      protoporphyrin (ZPP), urinary Sb (SbU), and the urinary As species in exposed
      workers and controls. PbA (12-42 MUg/m3) and AsA (1-4 MUg/m3) were strongly
      correlated (r = .95). PbB, ZPP, and the sum of As3+As5+MMA were significantly
      higher in the exposed workers. As3 was higher than the limit of detection in 14
      exposed workers and 1 control, As5 only in 1 exposed worker, SbU in all the
      exposed workers and in 4 controls. Monitoring for more metallic elements reveals
      a wider spectrum of exposures than can be achieved by lead surveillance alone and
      is preferable for characterizing occupational risk wherever possible.

PMID- 28443784
TI  - Robotic Characterization of Ipsilesional Motor Function in Subacute Stroke.
AB  - BACKGROUND: Poststroke impairments of the ipsilesional arm are often discussed,
      but rarely receive focused rehabilitation. Ipsilesional deficits may affect daily
      function and although many studies have investigated them in chronic stroke, few
      characterizations have been made in the subacute phase. Furthermore, most studies
      have quantified ipsilesional deficits using clinical measures that can fail to
      detect subtle, but important deficits in motor function. OBJECTIVE: We aimed to
      quantify reaching deficits of the contra- and ipsilesional limbs in the subacute
      phase poststroke. METHODS: A total of 227 subjects with first-time, unilateral
      stroke completed a unilateral assessment of motor function (visually guided
      reaching) using a KINARM robot. Subjects completed the task with both the ipsi-
      and contralesional arms. Subjects were assessed on a variety of traditional
      clinical measures (Functional Independence Measure, Chedoke-McMaster Stroke
      Assessment, Purdue Pegboard, Behavioral Inattention Test) to compare with robotic
      measures of motor function. RESULTS: Ipsilesional deficits were common and
      occurred in 37% (n = 84) of subjects. Impairments of the ipsilesional and
      contralesional arm were weakly to moderately correlated on robotic measures.
      Magnitude of impairment of the contralesional arm was similar for subjects with
      and without ipsilesional deficits. Furthermore, we found that a higher percentage
      of subjects with right-hemisphere stroke had ipsilesional deficits and more
      subjects with left-hemisphere subcortical strokes did not have ipsilesional
      deficits. CONCLUSIONS: Magnitude of contralesional impairment and lesion location
      may be poor predictors of individuals with ipsilesional impairments after stroke.
      Careful characterization of ipsilesional deficits could identify individuals who
      may benefit from rehabilitation of the less affected arm.

PMID- 28443785
TI  - Acute and Long-Term Impact of High-Protein Diets on Endocrine and Metabolic
      Function, Body Composition, and Exercise-Induced Adaptations.
AB  - BACKGROUND: High-protein diets have been shown to improve body composition
      through alterations in satiety, muscle protein synthesis, and the thermic effect
      of food. AIM: Given these findings, the purpose of this review is to discuss the
      integration of the specific hormonal and metabolic effects of high-protein diets
      following both acute and long-term usage, especially with regard to body
      composition. METHODS: Full-text articles were obtained through PubMed by using
      the terms "high-protein diet and body composition," "high-protein diet and
      exercise," "high-protein diet risk," "high-protein diet side effects," "protein
      quality PDCAAS," "RDA for protein," and "daily protein recommendation." Articles
      were initially screened according to their title and abstract; careful evaluation
      of the full manuscripts was then used to identify relevant articles. RESULTS: The
      higher satiety exerted by high-protein diets is generated through increments in
      anorexigenic, as well as decrements in orexigenic hormones. Improvements in
      muscle mass are achieved by activation of muscle protein synthesis acting through
      the mTOR pathway. High thermic effect of food is caused due to necessary
      deamination, gluconeogenesis, and urea synthesis caused by high-protein diets.
      Interestingly, high-protein diets in both hypo- and normocaloric conditions have
      shown to improve body composition, whereas in combination with hypercaloric
      conditions does not seem to increase fat mass, when the excess energy comes from
      protein. CONCLUSIONS: High protein diets effectively improve body composition by
      acting through different pathways.

PMID- 28443786
TI  - Characterization of Volitional Electromyographic Signals in the Lower Extremity
      After Motor Complete Spinal Cord Injury.
AB  - BACKGROUND: Previous studies have demonstrated the presence of intact axons
      across a spinal cord lesion, even in those clinically diagnosed with complete
      spinal cord injury (SCI). These axons may allow volitional motor signals to be
      transmitted through the injury, even in the absence of visible muscle
      contraction. OBJECTIVE: To demonstrate the presence of volitional
      electromyographic (EMG) activity below the lesion in motor complete SCI and to
      characterize this activity to determine its value for potential use as a
      neuroprosthetic command source. METHODS: Twenty-four subjects with complete (AIS
      A or B), chronic, cervical SCI were tested for the presence of volitional below
      injury EMG activity. Surface electrodes recorded from 8 to 12 locations of each
      lower limb, while participants were asked to attempt specific movements of the
      lower extremity in response to visual and audio cues. EMG trials were ranked
      through visual inspection, and were scored using an amplitude threshold algorithm
      to identify channels of interest with volitional motor unit activity. RESULTS:
      Significant below-injury muscle activity was identified through visual inspection
      in 16 of 24 participants, and visual inspection rankings were well correlated to
      the algorithm scoring. CONCLUSIONS: The surface EMG protocol utilized here is
      relatively simple and noninvasive, ideal for a clinical screening tool. The
      majority of subjects tested were able to produce a volitional EMG signal below
      their injury level, and the algorithm developed allows automatic identification
      of signals of interest. The presence of this volitional activity in the lower
      extremity could provide an innovative new command signal source for implanted
      neuroprostheses or other assistive technology.

PMID- 28443787
TI  - Ultrasound-based motor control training for the pelvic floor pre- and post
      prostatectomy: Scoring reliability and skill acquisition.
AB  - AIM: This study documents a protocol designed to evaluate pelvic floor motor
      control in men with prostate cancer. It also aims to evaluate the reliability of
      therapists in rating motor control of pelvic floor muscles (PFMs) using real time
      ultrasound imaging (RUSI) video clips. We further determine predictors of
      acquiring motor control. METHODS: Ninety-one men diagnosed with prostate cancer
      attending a physiotherapy clinic for pelvic floor exercises were taught detailed
      pelvic floor motor control exercises by a physiotherapist using trans-abdominal
      RUSI for biofeedback. A new protocol to rate motor control skill acquisition was
      developed. Three independent physiotherapists assessed motor control skill
      attainment by viewing RUSI videos of the contractions. Inter-rater reliability
      was evaluated using intra-class correlation coefficients. Logistic regression
      analysis was conducted to identify predictors of successful skill attainment.
      Acquisition of the skill was compared between pre- and post-operative
      participants using an independent-group t-test. RESULTS: There was good
      reliability for rating the RUSI video clips (ICC 0.73 (95%CI 0.59-0.82)) for
      experienced therapists. Having low BMI and being seen pre-operatively predicted
      motor skill attainment, accounting for 46.3% of the variance. Significantly more
      patients trained pre-operatively acquired the skill of pelvic floor control
      compared with patients initially seen post-operatively (OR 11.87, 95%CI 1.4 to
      99.5, p = 0.02). CONCLUSIONS: A new protocol to evaluate attainment of pelvic
      floor control in men with prostate cancer can be assessed reliably from RUSI
      images, and is most effectively delivered pre-operatively.

PMID- 28443788
TI  - The TIDieR checklist will benefit the physiotherapy profession.

PMID- 28443789
TI  - Teaching physiotherapy students to "be content with a body that refuses to hold
      still".
AB  - In recent decades, physiotherapists have become concerned with cultural,
      economic, philosophical, political, and social questions and have been exploring
      more flexible ways of speaking about and practicing physiotherapy. While
      recognizing the need to embrace a broader range of perspectives, physiotherapy
      educators and other medical educators have been at a loss as to how to best
      achieve this. Drawing on two examples from South Africa and New Zealand, we seek
      to illustrate possibilities and barriers to teaching social sciences to
      physiotherapy students, specifically theories of embodiment as an alternative to
      the biopsychosocial model. We review each educator's choice of embodiment theory
      in curriculum design and the role of the educator's disciplinary background on
      teaching, learning, and assessing that learning. Against this background, we
      explore physiotherapy students' experiences with theories of embodiment and
      possible transformative implications for their self-worth and/or professional
      practices. We suggest that students were able to explore physiotherapy's relation
      to the body and the profession's historical inattention toward the body as a
      philosophical/theoretical construct. From the lessons learned, some can perhaps
      be usefully passed onto others thinking of introducing a more diverse and
      inclusive approach of the body; one that we argue will be needed in the future.

PMID- 28443790
TI  - Do Pilates-based exercises following total knee arthroplasty improve postural
      control and quality of life?
AB  - PURPOSE: The aim of this prospective, randomized, controlled study was to
      investigate the effects of the addition of Pilates-based exercises to standard
      exercise programs performed after total knee arthroplasty on quality of life and
      balance. METHOD: Forty-six volunteers were divided into two groups. The control
      group (n = 17) was assigned a standard exercise program after discharge; the
      study group (n = 17) was assigned Pilates-based exercises along with the standard
      exercise program. We carried out clinical evaluations of all patients on the day
      of discharge and after the completion of the 6-week exercise program. We also
      recorded sociodemographic data, Berg Balance test scores, and Short Form-36 (SF
      36) health-related quality of life measurements. RESULTS: When we compared the
      differences between pre- and post-treatment balance scores of the groups, we
      found a significant change in favor of the Pilates-based exercise group (13.64 +/
      1.45; p < 0.01). The changes in the pre- and post-treatment SF-36 scores of the
      Pilates-based exercises group were found to be significant in terms of physical
      function (p = 0.001), physical role restriction (p = 0.01), and physical
      component score (p = 0.001). CONCLUSIONS: Pilates-based exercises performed along
      with standard exercise programs were more effective for improving balance and
      quality of life than standard exercise programs alone.

PMID- 28443791
TI  - Use of Speech-Generating Devices: In Support of Natural Speech.
AB  - One of the most frequently cited concerns from parents, teachers, and other
      caregivers, upon hearing a recommendation for the use of augmentative and
      alternative communication (AAC) is, 'Will its use interfere with natural speech?'
      Reports of positive effects of AAC use, particularly that of speech output, are
      increasingly available, whereas evidence to support negative consequences of AAC
      use has not been widely reported. In this paper, possible explanations for
      increases in natural speech production associated with AAC use are explored,
      along with a discussion of clinical implications and future research.

PMID- 28443792
TI  - Issues Affecting Staff Enhancement of Speech-Generating Device Use Among People
      with Severe Cognitive Disabilities.
AB  - This paper focuses on the role of human service staff when supporting individuals
      with severe disabilities who use speech-generating devices (SGDs) for functional
      communication. Following a brief overview of research that demonstrates the
      efficacy of SGDs within this group, a summary is provided of skills staff require
      to help ensure that individuals with severe disabilities have opportunities to
      use SGDs in effective ways. A competency- and performance-based training model
      (based on adult learning principles) which has evolved through applied research
      is discussed in relation to providing relevant skills training. An applied
      research-based model for supervising and monitoring staff performance of SGD
      related duties and responsibilities is also presented. Directions for future
      research, aimed at further enhancing the capacity of human service personnel to
      support people with severe cognitive disabilities in using SGDs, are noted.

PMID- 28443793
TI  - Effects of Speech Output on Maintenance of Requesting and Frequency of
      Vocalizations in Three Children with Developmental Disabilities.
AB  - We evaluated the role of digitized speech output on the maintenance of requesting
      and frequency of vocalizations in three children with developmental disabilities.
      The children were taught to request access to preferred objects using an
      augmentative communication speech-generating device (SGD). Following acquisition,
      rates of requesting and vocalizations were compared across two conditions (speech
      output on versus speech output off) that were alternated on a session-by-session
      basis. There were no major or consistent differences across the two conditions
      for the three children, suggesting that access to preferred objects was the
      critical variable maintaining use of the SGDs. The results also suggest that
      feedback in the form of digitized speech from the SGD did not inhibit
      vocalizations. One child began to speak single words during the latter part of
      the study, suggesting that in some cases AAC intervention involving SGDs may
      facilitate speech.

PMID- 28443794
TI  - Synthetic Speech Perception in Individuals With and Without Disabilities.
AB  - Individuals with little or no functional speech frequently rely on non-speech
      communication systems to augment or replace natural speech. These systems include
      speech generating devices (SGDs), which provide synthetic speech upon activation.
      This paper comprises a summary of research conducted over the past 20 years on
      the perception of synthetic speech by nondisabled listeners and listeners with
      intellectual, language, and hearing impairments. A wide variety of perceptual
      studies have been conducted into how human listeners understand synthetic speech.
      Research has shown that perceptions of synthetic speech in individuals with
      intellectual and/or language impairments depend upon several general factors,
      including the acoustic-phonetic properties of the synthesizer, complexity of the
      perceptual task, and the experience of the listener. Additionally, individuals
      with intellectual and/or language impairments exhibit greater difficulties than
      nondisabled listeners with regard to processing synthetic speech signals that
      impose substantial cognitive demands.

PMID- 28443795
TI  - Roles of Speech Output in Augmentative and Alternative Communication: Narrative
      Review.
AB  - Speech output from speech-generating devices (SGD) and SGD software, such as
      talking word processors, has changed the landscape of options for aided
      communication. The purpose of this paper is to review and critique research into
      the roles of speech output for communication partners, learners, and learner
      partner dyads. Research on partner - oriented roles is reviewed in terms of
      attitudes and perceived communicative competence, and communicative behavior.
      Learner-oriented roles of speech output are summarized in terms of graphic symbol
      learning, communicative functions and social regulation, learner preference,
      challenging behaviors, natural speech production, comprehension, and literacy.
      Roles for the learner - partner dyad include changes to interaction patterns.
      Methodological issues are discussed and practical implications are drawn where
      appropriate. Finally, directions for future research are proposed.

PMID- 28443796
TI  - A New Look AAC.

PMID- 28443797
TI  - Immunotherapy coming of age: notable advances during the first hundred years.

PMID- 28443801
TI  - Lipopolysaccharide-inducible Gene Expression Profile in Human Monocytes.
AB  - Monocytes/macrophages play a key role in host defense by phagocytosing invaded
      pathogens, presenting antigens to immune cells and producing numerous
      inflammatory mediators. Although the expression of many proteins and genes has
      been described to be up-regulated in activated human monocytes, a complete
      picture of the pathophysiological function of activated human monocytes has not
      yet been drawn. In this study the serial analysis of gene expression (SAGE)
      procedure was applied to lipopolysaccharide (LPS)-stimulated human monocytes. A
      total of 35,874 tags corresponding to more than 12,000 different transcripts was
      sequenced. In addition, the Long SAGE procedure was conducted in LPS-stimulated
      monocytes to increase the accuracy of corresponding gene identification.
      Comparison of the gene expression profile with that of resting monocytes revealed
      the whole LPS-inducible gene expression profile. The functional classifications
      of LPS-inducible genes (>=8-fold increase compared with resting monocytes) in
      monocytes showed that 25% of inducible genes were identified to encode cytokines
      and chemokines, followed by proteins related to metabolism (11%), cell surface
      antigens (9%), nuclear proteins (8%), proteases (6%), proteins related to
      extracellular transport (4%) and intracellular transducers (4%). Moreover, 14% of
      LPS-inducible genes still encode proteins with unknown function. This study
      represents the first global analysis of LPS-inducible genes in human monocytes
      and provides tremendous novel information for the function of LPS-activated
      monocytes and targets for diagnosing, monitoring and treating sepsis and various
      human infectious and inflammatory diseases.

PMID- 28443802
TI  - Fas-Ligand Mediated Apoptosis in Severe Sepsis and Shock.
AB  - Alterations in the apoptotic process in lymphoid tissues is a common condition
      which is encountered in the severely septic animal and critically ill patient.
      Here we attempt to delineate the pathological significance of these apoptotic
      changes and the role of Fas-FasL mediated contribution to this process.

PMID- 28443803
TI  - A strategy for early-risk predictions of clinical drug-drug interactions
      involving the GastroPlusTM DDI module for time-dependent CYP inhibitors.
AB  - 1. A set of reference compounds for time-dependent inhibition (TDI) of cytochrome
      P450 with available literature data for kinact and KI was used to predict
      clinical implications using the GastroPlusTM software. Comparisons were made to
      in vivo literature interaction data. 2. The predicted AUC ratios
      (AUC+inhibitor/AUCcontrol) could be compared with the observed ratios from
      literature for all compounds with detailed information about in vivo
      administration, pharmacokinetics and in vivo interactions (N = 21). For this
      dataset, the difference between predicted and observed AUC ratios for
      interactions with midazolam was within twofold for all compounds except one
      (telaprevir, for which non-CYP-mediated metabolism likely plays a role after
      multiple dosing). 3. The sensitivity, specificity and accuracy of the
      GastroPlusTM predictions using a binary classification as no-to-weak interaction
      versus moderate-to-strong interaction for all compounds with available in vivo
      interaction data, were 80%, 82% and 81%, respectively (N = 31). 4. As a result of
      our evaluations of the DDI module in GastroPlusTM, we have implemented an early
      TDI risk assessment decision tree for our drug discovery projects involving in
      vitro screening and early GastroPlusTM predictions. Shifted IC50 values are
      determined and kinact/KI estimated (by using a regression line established with
      in house-shifted IC50 values and literature kinact/KI ratios), followed by
      GastroPlusTM predictions.

PMID- 28443805
TI  - [A population-targeted approach to connect prevention, care and welfare:
      visualising the trend].
AB  - OBJECTIVE: To map initiatives in the Netherlands using a population-targeted
      approach to link prevention, care and welfare. DESIGN: Descriptive investigation,
      based on conversations and structured interviews. METHOD: We searched for
      initiatives in which providers in the areas of prevention, care and welfare
      together with health insurers and/or local authorities attempted to provide the
      'triple aim': improving the health of the population and the quality of care, and
      managing costs. We found potential initiatives on the basis of interviews with
      key figures, project databases and congress programmes. We looked for additional
      information on websites and via contact persons to gather additional information
      to determine whether the initiative met the inclusion criteria. An initiative
      should link prevention, care and welfare with a minimum of three players actively
      pursuing a population-targeted goal through multiple interventions for a non
      disease specific and district-transcending population. We described the goal,
      organisational structure, parties involved, activities and funding on the basis
      of interviews conducted in the period August-December 2015 with the managers of
      the initiatives included. RESULTS: We found 19 initiatives which met the criteria
      where there was experimentation with organisational forms, levels of
      participation, interventions and funding. It was noticeable that the
      interventions mostly concerned medical care. There was a lack of insight into the
      'triple aim', mostly because data exchange between parties is generally
      difficult. CONCLUSION: There is an increasing number of initiatives that follow a
      population-targeted approach. Although the different parties strive to connect
      the three domains, they are still searching for an optimal collaboration,
      organisational form, data exchange and financing.

PMID- 28443804
TI  - 25(OH)D Levels in Relation to Gender, Overweight, Insulin Resistance, and
      Inflammation in a Cross-Sectional Cohort of Northern Italian Workers: Evidence in
      Support of Preventive Health Care Programs.
AB  - OBJECTIVE: In recent years, the welfare of workers and the prevention of chronic
      disabling diseases has become a topic of great interest. This study investigates
      serum levels of total 25-hydroxyvitamin D (25(OH)D) in a cohort of overweight
      obese and insulin-resistant northern Italian indoor workers in apparent good
      health followed a nutritional education program. METHODS: An observational cross
      sectional study on 385 patients (females = 291, males = 94), age range 18-69
      years and body mass index (BMI) > 25 kg/m2, was performed at the Department of
      Occupational Medicine Milan, Italy, latitude 45.465454 N. We evaluated
      nutritional intakes, occupational and leisure physical activity, anthropometric
      measurements, impedance evaluation, blood pressure, the presence of metabolic
      syndrome (MetS) and nonalcoholic fatty liver diseases (NAFLD) by fatty liver
      index (FLI). Hematologic and biochemical parameters and (25(OH)D) levels were
      evaluated from fasting blood samples. RESULTS: Only 10.91% of subjects had
      optimal values of 25(OH)D; 17.40% of the remaining 89.09% subjects were severely
      deficient, with no gender difference and insufficient intake of vitamin D. Only
      28% declared leisure physical activity; 39.48% had metabolic syndrome and 62.60%
      had an FLI > 30. An inverse relationship between 25(OH)D levels and BMI was
      found, with a significant reduction of total 25(OH)D serum concentrations in
      winter. The homeostasis model assessment-insulin resistance (HOMA-IR) is
      positively related to BMI and inversely related to 25(OH)D concentrations. A
      positive correlation between vitamin D and leisure physical activity was found.
      At univariate analysis adjusted for age, gender and BMI, an inverse relationship
      between vitamin D and FLI was observed in both genders. The correlation between
      25(OH)D levels, inflammation markers, BMI, and FLI showed an increased risk of
      cardiovascular disease in this cohort of workers. CONCLUSION: Our results suggest
      the rationale for a large-scale screening program for vitamin D by means of
      easily implementable low-cost preventive supplementation.

PMID- 28443806
TI  - [Influence of smoking on pharmacokinetics of medication].
AB  - - In a previous issue, a case report was presented in the Dutch Journal of
      Medicine (NTvG) of a patient who had variable clozapine levels after switching
      from regular cigarettes to an e-cigarette and vice versa.- Besides clozapine
      there are a number of other agents with a narrow therapeutic range where
      pharmacokinetics can be influenced by smoking.- This review describes the
      mechanisms of smoking-induced influence on the pharmacokinetics of medicines, and
      guidance will be provided regarding which medicines must be monitored more
      closely when patients change their smoking habits.- Finally, an overview is given
      on package insert information concerning dose adjustments for smokers and non
      smokers.

PMID- 28443807
TI  - [Persistent, therapy-resistant conjunctivitis: consider infection with Chlamydia
      trachomatis].
AB  - Conjunctivitis is a frequently diagnosed disease, usually caused by a virus. A
      less well-known cause is a chlamydia infection. This may result in missed
      diagnoses, delay of treatment and several complications. We present two cases of
      a persistent, therapy-resistant conjunctivitis in patients who were over 70 years
      of age. One patient had conjunctival follicles, characteristic of chlamydia
      conjunctivitis. The polymerase chain reaction tests of conjunctival samples from
      both patients were positive for chlamydia. Both patients and their sexual
      partners were treated with oral azithromycin. There was a treatment delay in both
      cases due to late recognition which was partially due to the older age of the
      patients. These cases illustrate that when a patient presents with persistent,
      therapy-resistant conjunctivitis, particularly if conjunctival follicles are
      present, chlamydial conjunctivitis should be considered and conjunctival swabs
      should be taken, no matter what the age of the patient.

PMID- 28443808
TI  - [10 tips for improving patient handovers from hospital to other health care
      settings].
AB  - When patients are transferred from the hospital to other health care settings,
      responsibility for the patient is transferred from the treating physician, nurse,
      paramedic or pharmacist at the hospital to the next health care provider. Good
      patient handovers from hospital to other healthcare settings are essential to
      ensure continuity of care. However, handovers are often delayed or incomplete and
      the patient is barely involved in her or his own transfer. Risks related to an
      incomplete handover may be considerable. More than half of the preventable
      adverse events that occur after discharge are attributable to ineffective
      communication between hospital and other healthcare providers. Through the
      implementation of some adjustments, the discharge process can become a point of
      focus during a patient's hospital stay. Examples to improve patient handovers are
      standardizing the discharge process and the content of patient handovers,
      planning a target discharge date, starting the collection of transfer data on
      time and involving the patient in her or his transfer.

PMID- 28443809
TI  - [Twenty years of combination antiretroviral therapy for HIV infection in the
      Netherlands: progression and new challenges].
AB  - Due to the introduction of combination antiretroviral therapy (cART) 20 years
      ago, HIV infection in the Netherlands has changed from a fatal disease to a
      chronic condition with a near normalized life expectancy. The average age of HIV
      positive patients continues to increase, as does the prevalence of non-HIV
      related comorbidity. The number of new HIV diagnoses seems to be decreasing in
      the Netherlands, which is partly due to increased testing, earlier diagnosis,
      prompt cART initiation, and achievement of high levels of viral suppression,
      resulting in a reduced likelihood of onward transmission. In order to further
      curb the epidemic, it is important that as yet undiagnosed people living with HIV
      are identified as soon as possible. All practicing physicians in the Netherlands
      can contribute to this goal.

PMID- 28443810
TI  - [Transient monocular vision loss].
AB  - Transient monocular vision loss (TMVL) caused by temporary disturbance of blood
      flow to the retina is a harbinger of future vascular complications. The diagnosis
      may be difficult, not only because it is solely dependent on history taking, but
      also because the range of monocular visual symptoms a patient may experience is
      wide. The classic pattern of a sudden black or grey visual field, or a curtain
      that is drooping in front of one eye, easily fits in the diagnosis of TMVL;
      however, coloured vision or flashes should not always be considered as benign.
      The distinction between visual symptoms of one or both eyes should receive
      attention during history taking. It is the professional expertise of the
      neurologist and ophthalmologist which should make it possible to establish the
      correct diagnosis. A patient suspected of a retinal TIA should be evaluated and
      treated with the same urgency as someone with a cerebral TIA.

PMID- 28443811
TI  - [Shared decision-making: dilemmas in daily practice].
AB  - Shared decision-making is an essential - but often neglected - component of
      evidence-based medicine. In practice, doctors, nurses and patients encounter
      dilemmas which are understandable, but not insurmountable. We illustrate this by
      means of a complex decision concerning therapy in the advanced stage of
      Parkinson's disease. Evidence of effectiveness differs with each individual
      therapy, and, in practice, the experiences of neurologists also vary widely. In
      addition, the various treatment strategies all require a different sort of daily
      care, and have differing impacts on people's lives. It is time that we worked
      towards a realistic view of shared decision-making. Shared decision-making cannot
      be generalised to a 'one size fits all' strategy that we can choose to apply or
      not to apply at will. It should be a flexible instrument which, depending on the
      individual and the specific situation, can be put to use to deliver the best
      tailored care.

PMID- 28443812
TI  - Enhancing ethanol yields through d-xylose and l-arabinose co-fermentation after
      construction of a novel high efficient l-arabinose-fermenting Saccharomyces
      cerevisiae strain.
AB  - Lignocellulose contains two pentose sugars, l-arabinose and d-xylose, neither of
      which is naturally fermented by first generation (1G) ethanol-producing
      Saccharomyces cerevisiae yeast. Since these sugars are inaccessible to 1G yeast,
      a significant percentage of the total carbon in bioethanol production from plant
      residues, which are used in second generation (2G) ethanol production, remains
      unused. Recombinant Saccharomyces cerevisiae strains capable of fermenting d
      xylose are available on the market; however, there are few examples of l
      arabinose-fermenting yeasts, and commercially, there are no strains capable of
      fermenting both d-xylose and l-arabinose because of metabolic incompatibilities
      when both metabolic pathways are expressed in the same cell. To attempt to solve
      this problem we have tested d-xylose and l-arabinose co-fermentation. To find
      efficient alternative l-arabinose utilization pathways to the few existing ones,
      we have used stringent methodology to screen for new genes (metabolic and
      transporter functions) to facilitate l-arabinose fermentation in recombinant
      yeast. We demonstrate the feasibility of this approach in a successfully
      constructed yeast strain capable of using l-arabinose as the sole carbon source
      and capable of fully transforming it to ethanol, reaching the maximum theoretical
      fermentation yield (0.43 g g-1). We demonstrate that efficient co-fermentation of
      d-xylose and l-arabinose is feasible using two different co-cultured strains, and
      observed no fermentation delays, yield drops or accumulation of undesired
      byproducts. In this study we have identified a technically efficient strategy to
      enhance ethanol yields by 10 % in 2G plants in a process based on C5 sugar co
      fermentation.

PMID- 28443813
TI  - Vacuolar H+-ATPase subunit Vma1p functions as the molecular ligand in the vacuole
      targeting fungicidal activity of polymyxin B.
AB  - Polymyxin B (PMB) is a cationic cyclic peptide that can selectively inhibit the
      growth of Gram-negative bacteria by disrupting the outer membrane permeability
      barrier through binding to lipopolysaccharide (LPS). Here, a fluorescent PMB
      derivative (PMB-Ds) was applied to visually confirm the vacuole as a direct
      lethal target of PMB against fungal cells, which lack LPS. PMB-Ds could be
      visualized in the normal rounded vacuolar membrane of Saccharomyces cerevisiae
      cells, suggesting the presence of a molecular ligand assisting the vacuole
      targeting mobilization of the peptide in the organism. Vma1p, a cytoplasmic
      subunit constituent of the yeast vacuolar-type ATPase, was identified as one of
      the PMB-binding proteins by means of mass spectrometry. Mutant cells carrying a
      deletion of Vma1p but not those with deletions in two separate PMB-binding
      proteins were shown to be resistant to the vacuolar membrane disruptive action of
      PMB. Furthermore, the mutant cells were resistant to PMB lethality even when
      treated with PMB in combination with allicin, an allyl sulfur compound, which can
      selectively enhance the vacuole-targeting fungicidal activity of the peptide. In
      contrast, the parent cells were not made resistant to the vacuolar membrane
      disruptive action of PMB even if cells were pre-treated with bafilomycin A1, a
      specific inhibitor of the yeast vacuolar-type H+-ATPase. However, the parent
      cells were rendered more resistant to PMB consequent to Vma1p-GFP localization in
      the cytoplasm. These findings suggested a role for Vma1p in the vacuole-targeting
      fungicidal activity of PMB comparable to that of LPS in the outer membrane of
      Gram-negative bacteria.

PMID- 28443814
TI  - Neural networks subtract and conquer.
AB  - Two theoretical studies reveal how networks of neurons may behave during reward
      based learning.

PMID- 28443815
TI  - Molecular mechanism of voltage-dependent potentiation of KCNH potassium channels.
AB  - EAG-like (ELK) voltage-gated potassium channels are abundantly expressed in the
      brain. These channels exhibit a behavior called voltage-dependent potentiation
      (VDP), which appears to be a specialization to dampen the hyperexitability of
      neurons. VDP manifests as a potentiation of current amplitude, hyperpolarizing
      shift in voltage sensitivity, and slowing of deactivation in response to a
      depolarizing prepulse. Here we show that VDP of D. rerio ELK channels involves
      the structural interaction between the intracellular N-terminal eag domain and C
      terminal CNBHD. Combining transition metal ion FRET, patch-clamp fluorometry, and
      incorporation of a fluorescent noncanonical amino acid, we show that there is a
      rearrangement in the eag domain-CNBHD interaction with the kinetics, voltage
      dependence, and ATP-dependence of VDP. We propose that the activation of ELK
      channels involves a slow open-state dependent rearrangement of the direct
      interaction between the eag domain and CNBHD, which stabilizes the opening of the
      channel.

PMID- 28443816
TI  - Segmental volvulus in the neonate: A particular clinical entity.
AB  - BACKGROUND: Complete intestinal volvulus is mainly related to congenital
      anomalies of the so-called intestinal malrotation, whereas segmental volvulus
      appears as a distinct entity, mostly observed during the perinatal period.
      Because these two situations are still lumped together, the aim of this study was
      to describe the particular condition of neonatal segmental volvulus. STUDY
      DESIGN: We analyzed the circumstances of diagnosis and management of 17
      consecutives neonates operated for segmental volvulus more than a 10-year period
      in a single institution. During the same period, 19 cases of neonatal complete
      midgut volvulus were operated. RESULTS: Prenatal US exam anomalies were observed
      in 16/17 (94%) of segmental volvulus, significantly more frequently than in
      complete volvulus (p=0.003). Intestinal malposition was described peroperatively
      in all cases of complete volvulus, but also in 4/17 segmental volvulus (23%).
      Intestinal resection was performed in 88% of segmental volvulus when only one
      extensive intestinal necrosis was observed in complete volvulus. Parenteral
      nutrition was required in all patients with segmental volvulus with a median
      duration of 50days (range 5-251). CONCLUSION: Segmental volvulus occurs mainly
      prenatally and leads to fetal ultrasound anomalies. This situation, despite a
      limited length of intestinal loss, is associated to significant postnatal
      morbidity. TYPE OF THE STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.

PMID- 28443817
TI  - Childhood Sustained Hypercalcemia: A Diagnostic Challenge.
AB  - OBJECTIVE: This study aimed to call attention to hypercalcemia, a rare finding in
      children which carries the potential of leading to serious complications without
      proper intervention. METHODS: Diagnosis, treatment, and clinical course of
      children with sustained hypercalcemia admitted between the years 2006-2016 were
      reviewed. Group 1 [parathyroid hormone (PTH)-dependent] consisted of patients
      with high/unsuppressed PTH levels and group 2 (PTH-independent) included cases
      with normal/suppressed PTH levels. RESULTS: Twenty patients (11 male, 9 female)
      with a median age of 6.25 (0.03-17.88) years were evaluated. Symptoms were mostly
      related with the gastrointestinal system, while six patients (30%) were
      asymptomatic. Physical examination findings were diverse, non-specific, and
      normal in four patients (20%). Median time of diagnosis was 45 (2-720) days.
      Patients were divided into group 1 (n=7) and group 2 (n=13). Most frequent
      etiologies were primary hyperparathyroidism (n=5), idiopathic infantile
      hypercalcemia (IIH) (n=5), and malignancy (n=4). A moderate positive correlation
      was noted between serum calcium and creatinine levels (r=0.53, p=0.02).
      Nephrocalcinosis was the most common complication (n=9) (45%). Treatment was not
      implemented in 2 patients with mild hypercalcemia, while other patients received
      medical treatment +/- surgery. Treatment-resistant patients were cases of
      malignancies and neonatal severe hyperparathyroidism. Long-term follow-up
      displayed resistant hypercalciuria in three infants diagnosed as IIH. CONCLUSION:
      Many patients with childhood hypercalcemia are asymptomatic or exhibit a non
      specific and heterogeneous clinical presentation, resulting in delayed diagnosis.
      Mild cases may not be recognized, while symptoms may be missed in the presence of
      accompanying illnesses. Nevertheless, serious complications may only be avoided
      with prompt diagnosis and intervention.

PMID- 28443818
TI  - Implementation of an ISBT 128-Compatible Medical Record System to Facilitate
      Traceability of Stem Cell Products.

PMID- 28443819
TI  - A Rare Late Complication of Port Catheter Implantation: Embolization of the
      Catheter.

PMID- 28443820
TI  - A Comprehensive Online Calculator for Pediatric Endocrinologists: CEDD
      Cozum/TPEDS Metrics.

PMID- 28443821
TI  - Two new species of Tetragonocephalum (Cestoda: Lecanicephalidea) from Pastinachus
      sephen (Myliobatiformes: Dasyatidae) from the Gulf of Oman.
AB  - In the present study two new species of Tetragonocephalum Shipley et Hornell,
      1905, T. mackenziei sp. n. and T. kazemii sp. n., are described from the spiral
      intestine of the cowtail stingray, Pastinachus sephen (Forsskal), from the
      northern coast of the Gulf of Oman. Tetragonocephalum mackenziei is distinguished
      from the 16 other valid species of Tetragonocephalum by a unique combination of
      characteristics, i.e. sperm-filled seminal receptacle in immature proglottids,
      body length (7.7-17.5 mm), body width (213-288 um), number of proglottids (34
      49), number of testes (10-14), size of scolex (228-315 um * 213-288 um) and size
      of acetabula (56-73 um * 61-75 um). Tetragonocephalum kazemii is morphologically
      distinguishable from its valid congeners and T. mackenziei based on a combination
      of characteristics, including body length (28.8-36.6 mm), number of proglottids
      (50-65), number of testes (30-42), size of scolex (388-564 um * 326-448 um), size
      of acetabula (62-86 um * 57-90 um) and testes (25-39 * 21-32). This brings the
      total number of validly described species of Tetragonocephalum to 18 and expands
      our knowledge of this diverse genus to now include the Gulf of Oman, as well as
      Arafura Sea, northern Indian Ocean and western Pacific Ocean.

PMID- 28443822
TI  - An eight-year survey of the intestinal parasites of carnivores, hoofed mammals,
      primates, ratites and reptiles in the Ljubljana zoo in Slovenia.
AB  - Problems with parasitic infections and their interspecies transmissions are
      common in zoological gardens and could pose serious health damage to captive
      animals. This study presents results of eight-year monitoring of intestinal
      parasites in animals from Zoo Ljubljana, Slovenia. A total of 741 faecal samples
      from 40 animal species were collected two to four times per year and examined
      microscopically. Intestinal parasites were detected in 45% of samples, with
      detection of helminths (Cestoda, Nematoda - Ascaridida, Enoplida, Strongylida,
      Oxyurida, Rhabditida and Trichurida) and protists (Apicomplexa and Ciliophora) in
      25% and 13% of samples, respectively; mixed infection was found in 7% of samples.
      The mostly infected were ungulates (61%), followed by reptiles (44%), ratites
      (29%), primates (22%) and carnivores (7%). During the observation period, the
      number of infected animal species increased from 8 to 25. This is the first long
      term monitoring study of intestinal parasites in zoo animals from Slovenia.
      Routine monitoring of parasitic infection and regular deworming and hygienic
      measures are necessary to prevent gastrointestinal infections in captive animals.

PMID- 28443823
TI  - Gene expression, oxidative stress and apoptotic changes in rabbit ileum
      experimentally infected with Eimeria intestinalis.
AB  - Coccidiosis is a parasitic disease caused by protists (apicomplexans) of the
      genus Eimeria Schneider, 1875 and is considered to be the most important disease
      faced by rabbit breeders due to its high morbidity. In the present study, the
      antioxidant status and changes in apoptosis and in the expression of some genes
      were quantified in rabbits' ilea following infection with Eimeria intestinalis
      Cheissin, 1948. Rabbits, orally infected with 1 * 105 sporulated oocysts of E.
      intestinalis, started to shed oocysts in their faeces on 8 days post infection
      (dpi) and reached maximum excretion on 10 dpi, with approximately 5 million
      oocysts. This was accompanied by a significant decrease in the live body weight
      of infected rabbits. Also, malondialdehyde and nitric oxide were significantly
      increased while catalase and glutathione were significantly decreased in the
      ileum tissues of the infected rabbits. In addition, a significant increase was
      observed in the percentages of apoptotic cells in the ilea of the infected
      rabbits. Furthermore, interleukin-1beta and interleukin-2 mRNA levels were
      significantly down-regulated and mRNA levels of interleukin-6, interferon gamma
      and inducible nitric oxide synthase were significantly up-regulated, while those
      of C-reactive protein remained unchanged. We conclude that infection with E.
      intestinalis induces oxidative stress, a significant increase in the percentage
      of apoptotic cells and a diverse and robust Th1 and Th1-related cytokine response
      in the ileum tissues.

PMID- 28443824
TI  - Stable charged antiparallel domain walls in hyperferroelectrics.
AB  - Charge-neutral 180 degrees  domain walls that separate domains of antiparallel
      polarization directions are common structural topological defects in
      ferroelectrics. In normal ferroelectrics, charged 180 degrees  domain walls
      running perpendicular to the polarization directions are highly energetically
      unfavorable because of the depolarization field and are difficult to stabilize.
      We explore both neutral and charged 180 degrees  domain walls in
      hyperferroelectrics, a class of proper ferroelectrics with persistent
      polarization in the presence of a depolarization field, using density functional
      theory. We obtain zero temperature equilibrium structures of head-to-head and
      tail-to-tail walls in recently discovered ABC-type hexagonal hyperferroelectrics.
      Charged domain walls can also be stabilized in canonical ferroelectrics
      represented by LiNbO3 without any dopants, defects or mechanical clamping. First
      principles electronic structure calculations show that charged domain walls can
      reduce and even close the band gap of host materials and support quasi-two
      dimensional electron(hole) gas with enhanced electrical conductivity.

PMID- 28443825
TI  - Anomalous magnetotransport behaviours in PtSe2 microflakes.
AB  - Platinum diselenide (PtSe2) is a newly discovered 2D transition metal
      dichalcogenide, and is further theoretically identified as a candidate of type-II
      Dirac semimetals. The electrical transport study of PtSe2 microflakes may provide
      great potential not only in fundamental physics, but also for future electronic
      applications. We report the anomalous magnetotransport properties of PtSe2
      microflakes. The anisotropic magnetoresistance of PtSe2 microflakes can be
      normalized by introducing a 3D scaling factor [Formula: see text], where theta is
      the magnetic field angle with respect to the c axis of the crystal and gamma is
      the mass anisotropic constant of electrons. Additionally, the non-monotonic
      temperature-dependent magnetoresistance of PtSe2 microflakes is observed both in
      the perpendicular and in-plane magnetic field orientations. This anomalous
      magnetotransport behaviour may be ascribed to the novel features of type-II Dirac
      fermions; however, the exact physical mechanism deserves further investigation.

PMID- 28443826
TI  - Rebinding in biochemical reactions on membranes.
AB  - The behavior of many biochemical processes depends crucially on molecules rapidly
      rebinding after dissociating. In the case of multisite protein modification, the
      importance of rebinding has been demonstrated both experimentally and through
      several recent computational studies involving stochastic spatial simulations. As
      rebinding stems from spatio-temporal correlations, theorists have resorted to
      models that explicitly include space to properly account for the effects of
      rebinding. However, for reactions in three space dimensions it was recently shown
      that well-mixed ordinary differential equation (ODE) models can incorporate
      rebinding by adding connections to the reaction network. The rate constants for
      these new connections involve the probability that a pair of molecules rapidly
      rebinds after dissociation. In order to study biochemical reactions on membranes,
      in this paper we derive an explicit formula for this rebinding probability for
      reactions in two space dimensions. We show that ODE models can use the formula to
      replicate detailed stochastic spatial simulations, and that the formula can
      predict ultrasensitivity for reactions involving multisite modification of
      membrane-bound proteins. Further, we compute a new concentration-dependent
      rebinding probability for reactions in three space dimensions. Our analysis
      predicts that rebinding plays a much larger role in reactions on membranes
      compared to reactions in cytoplasm.

PMID- 28443827
TI  - Three-dimensional magnetic interactions in quasi-two-dimensional PdAs2O6.
AB  - Millimeter-sized PdAs2O6 single crystals are grown using the vapor transport
      technique. The magnetic order at [Formula: see text] K is studied by measuring
      magnetic properties, specific heat, and neutron single crystal diffraction. The
      anisotropic magnetic susceptibility and a metamagnetic transition observed in
      magnetic fields above 20 kOe suggest that the magnetic moment lies in the ab
      plane, consistent with the magnetic structure determined by neutron single
      crystal diffraction. Below 140 K, Pd2+ ions order ferromagnetically in the ab
      plane but antiferromagnetically along the crystallographic c axis. The ordered
      moment is refined to be 2.09(2) [Formula: see text]/Pd2+ using the fitted
      magnetic form factor of Pd2+ . A weak lambda-type anomaly around T N was observed
      in specific heat and the magnetic entropy change across T N is 1.72 J mol-1
      K.This small entropy change and the temperature dependence of the magnetic
      susceptibility support the presence of short range correlations in a wide
      temperature range [Formula: see text] 250 K. The comparison with SrRu2O6 suggests
      that the magnetic interactions in PdAs2O6 are dominated by Pd-(O-[Formula: see
      text]-O)-Pd super-superexchange and three dimensional despite the quasi-two
      dimensional arrangement of magnetic ions. The comparison with NiAs2O6 suggests
      that increasing covalency of isostructural compounds is an effective approach to
      design and to discover new materials with higher magnetic order temperatures in
      the localized regime.

PMID- 28443828
TI  - Controlled synthesis of MnO2 nanosheets vertically covered FeCo2O4 nanoflakes as
      a binder-free electrode for a high-power and durable asymmetric supercapacitor.
AB  - We developed a simple and controlled method to synthesize FeCo2O4@MnO2 core
      sheath nanoarchitecture (CSN) grown on Ni foam. Ultrathin FeCo2O4 nanoflakes with
      an average thickness of 10 nm served as the scaffold to deposit the MnO2
      nanosheets. The MnO2 nanosheets were able to vertically grow on FeCo2O4
      nanoflakes to form a sheath via a hydrothermal reaction. The nanocomposites'
      thickness could be tailored from 80 nm-550 nm by changing the reaction times.
      Electrochemical measurements demonstrated that FeCo2O4@MnO2 CSN with an optimal
      thickness of about 400 nm achieved an areal capacitance of 3.077 F cm-2 at 2 mA
      cm-2, which is much higher than individual FeCo2O4 nanoflakes (0.295 F cm-2) and
      MnO2 nanosheets (1.065 F cm-2). An aqueous asymmetric supercapacitor (ASC) was
      assembled using FeCo2O4@MnO2 CSN as its positive electrode and activated carbon
      (AC) as its negative electrode. The FeCo2O4@MnO2?AC ASC exhibited a capacitance
      of 0.538 F cm-2 at 5 mA cm-2 with a potential window of 1.65 V, and an excellent
      cycling stability (99.1% retention even after 5000 cycles). Furthermore, the
      maximum energy density and power density of FeCo2O4@MnO2?AC ASC was 0.203 mWh cm
      2 at 3.44 mW cm-2 and 28.6 mW cm-2 at 0.061 mWh cm-2, respectively.

PMID- 28443829
TI  - Operating principles of tristable circuits regulating cellular differentiation.
AB  - Many cell-fate decisions during embryonic development are governed by a motif
      comprised of two transcription factors (TFs) A and B that mutually inhibit each
      other and may self-activate. This motif, called as a self-activating toggle
      switch (SATS), can typically have three stable states (phenotypes)-two
      corresponding to differentiated cell fates, each of which has a much higher level
      of one TF than the other-[Formula: see text] or [Formula: see text]-and the third
      state corresponding to an 'undecided' stem-like state with similar levels of both
      A and B-[Formula: see text]. Furthermore, two or more SATSes can be coupled
      together in various topologies in different contexts, thereby affecting the
      coordination between multiple cellular decisions. However, two questions remain
      largely unanswered: (a) what governs the co-existence and relative stability of
      these three stable states? (b) What orchestrates the decision-making of coupled
      SATSes? Here, we first demonstrate that the co-existence and relative stability
      of the three stable states in an individual SATS can be governed by the relative
      strength of self-activation, external signals activating and/or inhibiting A and
      B, and mutual degradation between A and B. Simultaneously, we investigate the
      effects of these factors on the decision-making of two coupled SATSes. Our
      results offer novel understanding into the operating principles of individual and
      coupled tristable self-activating toggle switches (SATSes) regulating cellular
      differentiation and can yield insights into synthesizing three-way genetic
      circuits and understanding of cellular reprogramming.

PMID- 28443830
TI  - PaCO2 measurement in cerebral haemodynamics: face mask or nasal cannulae?
AB  - OBJECTIVE: PaCO2 affects cerebral blood flow (CBF) and its regulatory mechanisms,
      but the effects of CO2 measurement technique on cerebrovascular parameters are
      unknown. In order to determine if the two most commonly used approaches, face
      mask (FM) or nasal cannulae (NC), are interchangeable or not, we tested the
      hypothesis that the use of FM versus NC does not lead to significant differences
      in CO2-related systemic and cerebrovascular parameters. APPROACH: Recordings of
      CBF velocity (CBFV), blood pressure (BP), heart rate, and end-tidal CO2 (EtCO2)
      were performed in 42 subjects during normocapnia (FM or NC) and 5% CO2 inhalation
      (FM) or hyperventilation (NC). Dynamic cerebral autoregulation was assessed with
      the autoregulation index (ARI), derived by transfer function analysis from the
      CBFV response to a hypothetical step change in BP. MAIN RESULTS: Significant
      differences in physiological parameters were seen between FM and NC: EtCO2 (37.40
      versus 35.26 mmHg, p  =  0.001) and heart rate (69.6 versus 66.7 bpm, p  = 
      0.001) respectively. No differences were observed for mean BP, CBFV or the ARI
      index. SIGNIFICANCE: Use of FM or NC for measurement of EtCO2 leads to
      physiological changes and differences in parameter values that need to be taken
      into consideration when interpreting and/or comparing results in studies of
      cerebral haemodynamics.

PMID- 28443831
TI  - Fabrication of size-controlled nanoring arrays by selective incorporation of
      ionic liquids in diblock copolymer micellar cores.
AB  - We report the synthesis of arrayed nanorings with tunable physical dimensions
      from thin films of polystyrene-block-poly(4-vinylpyridine) (PS-P4VP) micelles.
      For accurate control of the inner and outer diameters of the nanorings, we added
      imidazolium-based ionic liquids (ILs) into the micellar solution, which were
      eventually incorporated into the micellar cores. We observed the structural
      changes of the micellar cores coated on a substrate due to the presence of ILs.
      The spin-coated micellar cores were treated with an acidic precursor solution and
      generated toroid nanostructures, of which size depended on the amount of IL
      loaded into the micelles. We then treated the transformed micellar films with
      oxygen plasma to produce arrays of various metal and oxide nanorings on a
      substrate. The spacings and diameters of nanorings were governed by the molecular
      weight of the PS-P4VP and the amount of IL used. We also demonstrated that
      arrayed Pt nanorings enabled the fabrication of reduced graphene oxide anti
      nanoring arrays via a catalytic tailoring process.

PMID- 28443832
TI  - Protective Buffering Capacity of Restorative Dental Materials In Vitro.
AB  - PURPOSE: To investigate the buffering capacity of restorative materials during a
      simulated carious and intrinsic erosive attack. MATERIALS AND METHODS: Cavities
      with a volume of 130 MUl were milled (Cerec MC XL) out of blocks of Ceram X Mono
      (CM), Quixfil (QX), Filtek Supreme (FS), Apa Fill 3 (AF), an experimental dual
      curing composite containing a bioactive glass (EX), Dyract eXtra (DY), Beautifil
      (BE), Equia Fil (EQ), Telio CAD (TL) (negative control), TheraCal (TC; positive
      control), and extracted teeth (ED). 80 MUl of lactic acid (pH 4.5) and
      hydrochloric acid (pH 2.6) were each pipetted into the cavities of two samples of
      each material. Change of pH in the solutions was measured continuously for 12 min
      using a calibrated pH electrode. RESULTS: CM, AF, and FS (final pH 3.0-3.2)
      neutralized hydrochloric acid to a significantly lesser extent than did BE, EQ,
      DY and QX (final pH 5.0-5.6) (p < 0.05, ANOVA Scheffe). The lactic-acid buffering
      capacity of CM, BE, and AF was equivalent (final pH 6.3-7.4) to that of ED (7.5),
      but was surpassed by FS (pH 8.0). pH values for EX and TC (final pH 9.2-11.3)
      increased significantly (p < 0.05) in response to both acids. CONCLUSIONS:
      Conventional restorative materials do not buffer better than human teeth.
      However, the experimental composite demonstrates that buffering against carious
      and intrinsic erosive acid attacks is technically feasible.

PMID- 28443833
TI  - Bulk-Fill Composites: A Review of the Current Literature.
AB  - PURPOSE: The aim of this article was to provide an overview of the literature on
      the currently available bulk-fill composites, and to describe the common trends
      as well as the wide variations. The findings may help the clinician to select the
      proper material with regard to its applicability in various clinical situations.
      METHODS: The literature up to October 2016 was reviewed based on a PubMed search
      (keywords: "bulk-fill OR bulkfill OR bulk fill" AND "composite OR composites").
      RESULTS: This review revealed that bulk-fill composites differ most from
      conventional composites in their increased depth of cure, which could mainly be
      attributed to an increase in translucency. However, the literature is
      inconsistent regarding the determination of the depth of cure. Flowable "base"
      bulk-fill composites seem most suitable for narrow cavities deeper than 4 mm, in
      particular when a higher adaptation potential thanks to better flowability in
      less accessible cavity configurations is desirable. In more extensive cavities,
      "full-body" bulk-fill composites with a high filler load are preferable. Then,
      resistance against wear and fracture becomes increasingly important, while a
      thicker consistency might also help in obtaining a good contact point. Tests
      related to shrinkage stress induced by bulk-filling seem inconsistent and their
      clinical relevance is unclear. CONCLUSION: More clinical studies that
      specifically focus on bulk-filling deep and large restorations are definitely
      required to fully explore the clinical benefits of bulk-fill composites.

PMID- 28443834
TI  - Influence of Different Pretreatments on the Microtensile Bond Strength to Eroded
      Dentin.
AB  - PURPOSE: To evaluate the influence of different pretreatments on the microtensile
      bond strength (uTBS) of an etch-and-rinse adhesive to eroded dentin. MATERIALS
      AND METHODS: Thirty-six human teeth were ground down to their dentin layer and
      randomly divided into six groups (G1-G6; n = 6), G1 being the control group. Only
      in the test groups (G2-G6) were samples subjected to erosion using citric acid
      (pH 2.6) 10 x 2 min per day for five days. Between the erosive attacks, samples
      were stored in artificial saliva. After pretreatment - none (G1); none (G2); 2%
      chlorhexidine (30 s) (G3); prolonged primer application (1 min) (G4); roughening
      with a diamond bur (G5) and 10.5% NaOCl (1 min) (G6) - the adhesive OptiBond FL
      was applied. After the application of composite, samples were stored in water (7
      d) and uTBS was determined. Data were evaluated using one-way ANOVA and Dunnett-T
      post-hoc test (p < 0.05). RESULTS: Eroded dentin without pretreatment (G2)
      resulted in significant reduction of uTBS compared with uneroded dentin (G1).
      uTBS after pretreatment with a diamond bur (G5) or NaOCl (G6) was not
      significantly different from that of the uneroded control group (G1). uTBS after
      pretreatment with chlorhexidine (G3) or with prolonged primer application (G4)
      was significantly lower than in the uneroded control group (G1), and not
      significantly different from the eroded control group (G2). CONCLUSION: The
      present data suggests that uTBS to eroded dentin pretreated with bur abrasion or
      NaOCl is similar to the uTBS to sound, uneroded dentin.

PMID- 28443835
TI  - Effect of Boric Acid Versus Conventional Irrigation Solutions on the Bond
      Strength Between Fiber Post ?and Root Dentin.
AB  - PURPOSE: To compare the effect of boric acid solutions of different percentages
      to conventional irrigation solutions on the adhesive bond strength between fiber
      posts and radicular dentin surface with different cement types. MATERIALS AND
      METHODS: One hundred fifteen extracted human incisors were endodontically
      instrumented to a length of 14-15 mm, and 12-mm post spaces were prepared with
      specific drills. Cylindrical fiber posts (Panavia Post) were luted with two
      different composite cements (Panavia F 2.0, Panavia SA) and cut into 1-mm-thick
      slices. These specimens were randomly allocated to 5 groups according to the
      irrigant applied: 1. control, no irrigant; 2. 10 ml of 2% chlorhexidine; 3. 10 ml
      of 5.25% NaOCl for 5 min and 10 ml of 17% EDTA for 3 min; 4. 10 ml of 5% boric
      acid solution at a temperature of 55 degrees C for 60 s; 5. 10% boric acid
      solution, conditions as in group 4. Bond strength was determined using the push
      out test. Microscopic assessment and SEM evaluations were performed in
      combination with push-out tests. RESULTS: The push-out bond strengths of cervical
      segments were significantly higher than for the middle and apical segments in all
      groups. The type of irrigation solution used significantly affected the bond
      strengths of the posts. The 10% boric acid solution and EDTA + NaOCl irrigation
      solutions provided the highest bond strengths (p < 0.005). SEM analysis showed
      that the dentin tubules were open and the smear layer was completely removed when
      EDTA/NaOCl and 10% boric acid were used as irrigation agents. CONCLUSION: Boric
      acid solutions, especially at a concentration of 10%, can be a viable alternative
      to the conventional irrigants used during endodontic treatment. The extent to
      which the 10% boric acid solution successfully removed the smear layer and the
      ease of rinsing boric acid from the root surface are advantageous.

PMID- 28443836
TI  - Energy harvesting from aperiodic low-frequency motion using reverse
      electrowetting.
AB  - Mechanical energy harvesting can provide a promising alternative to
      electrochemical batteries, which are currently widely utilized to power mobile
      electronics. In this work we present a theoretical analysis of a recently
      proposed method of mechanical energy harvesting, which combines a reverse
      electrowetting phenomenon with the fast self-oscillating process of bubble growth
      and collapse. We investigate the details of the bubble dynamics and analyze the
      dependence of the energy generation process on the system parameters. The results
      demonstrate that self-oscillation frequencies of several kHz are possible, which
      can lead to very high power generation densities in excess of 104 W m-2. The
      obtained results indicate the possibility of high-power energy harvesting from
      mechanical energy sources with very low frequencies, well below 1 Hz.

PMID- 28443837
TI  - Real time plasmonic qPCR: how fast is ultra-fast? 30 cycles in 54 seconds.
AB  - Polymerase Chain Reaction (PCR) is a critical tool for biological research
      investigators but recently it also has been making a significant impact in
      clinical, veterinary and agricultural applications. Plasmonic PCR, which employs
      the very efficient heat transfer of optically irradiated metallic nanoparticles,
      is a simple and powerful methodology to drive PCR reactions. The scalability of
      next generation plasmonic PCR technology will introduce various forms of PCR
      applications ranging from small footprint portable point of care diagnostic
      devices to large footprint central laboratory multiplexing devices. In a
      significant advance, we have introduced a real time plasmonic PCR and explored
      the ability of ultra-fast cycling compatible with both label-free and
      fluorescence-based monitoring of amplicon production. Furthermore, plasmonic PCR
      has been substantially optimized to now deliver a 30 cycle PCR in 54 seconds,
      with a detectable product. The advances described here will have an immediate
      impact on the further development of the use of plasmonic PCR playing a critical
      role in rapid point of care diagnostics.

PMID- 28443838
TI  - Charge detection mass spectrometry: weighing heavier things.
AB  - Charge detection mass spectrometry (CDMS) is a single molecule method where the
      mass of each ion is directly determined from individual measurements of its mass
      to-charge ratio and charge. CDMS is particularly valuable for the analysis of
      high mass and heterogeneous analytes, where conventional MS methods are often
      confounded. In the last few years, CDMS has received a renaissance. Technical
      developments have improved the resolution and dramatically increased the breadth
      of problems that can be addressed. These improvements have moved CDMS more into
      the mainstream as interest in the application of mass spectrometry to high
      molecular weight species has grown. In the article, the three main variants of
      CDMS are described, along with an overview of recent applications.

PMID- 28443839
TI  - Phenolic compounds increase the transcription of mouse intestinal maltase
      glucoamylase and sucrase-isomaltase.
AB  - Diverse natural phenolic compounds show inhibition activity of intestinal alpha
      glucosidases, which may constitute the molecular basis for their ability to
      control systemic glycemia. Additionally, phenolics can modify mRNA expression for
      proteins involved in nutritional, metabolic or immune processes. To explore the
      possibility that phenolics can regulate the mRNA expression, enzymatic activity,
      and protein synthesis/processing of intestinal Maltase-Glucoamylase (MGAM) and
      Sucrase-Isomaltase (SI), small intestinal explants from Balb/c mice were cultured
      for 24 h in the presence or absence of gallic acid, caffeic acid, and (+)
      catechin at 0.1, 0.5, and 1 mM. We measured the levels of MGAM and SI mRNA
      expression by qRT-PCR, maltase and sucrase activities by a standard colorimetric
      method and the molecular size distribution of MGAM and SI proteins by western
      blotting. mRNA expression for MGAM was induced by the three phenolic compounds at
      0.1 mM. mRNA expression for SI was induced by caffeic and gallic acids, but not
      by (+)-catechin. Caffeic acid was the most effective inducer of mRNA expression
      of these enzymes. Total maltase and sucrase activities were not affected by
      treatment with phenolics. The proportion of high molecular size forms of MGAM was
      significantly increased by two of the three phenolic compounds, but little effect
      was observed on SI proteins. Thus, changes in the protein synthesis/processing,
      affecting the proportions of the different molecular forms of MGAM, may account
      for the lack of correlation between mRNA expression and enzymatic activity.

PMID- 28443840
TI  - Effect of incorporating flat aromatic molecules on spherical polymeric
      nanoparticles.
AB  - Flat aromatic structures are ubiquitous in organic semiconducting molecules. The
      possibility of endowing these inherently anisotropic molecules with isotropic
      structures is explored using a polymeric nanoparticle attachment strategy.
      Preliminary findings, outlined in this manuscript, suggest that this might be a
      simple and effective strategy for organic semiconductors with consistent
      mobilities.

PMID- 28443842
TI  - Pulsed valve matrix-assisted ionization.
AB  - We have developed a new ionization approach for matrix-assisted ionization with
      high temporal resolution using an electrically actuated pulsed valve. Matrix and
      analyte samples are deposited on a thin metal foil and placed at the inlet of an
      ambient ionization mass spectrometer. When the pulsed valve is actuated, a short
      puff of high pressure gas impinges on the foil and ejects particulate from the
      sample on the opposite side. Highly charged ions are formed from the particles at
      the mass spectrometer inlet. Using this source, multiply charged protein ions are
      produced within a selectable 4 second time window.

PMID- 28443841
TI  - Automatic concentration and reformulation of PET tracers via microfluidic
      membrane distillation.
AB  - Short-lived radiolabeled tracers for positron emission tomography (PET) must be
      rapidly synthesized, purified, and formulated into injectable solution just prior
      to imaging. Current radiosynthesizers are generally designed for clinical use,
      and the HPLC purification and SPE formulation processes often result in a final
      volume that is too large for preclinical and emerging in vitro applications.
      Conventional technologies and techniques for reducing this volume tend to be
      slow, resulting in radioactive decay of the product, and often require manual
      handling of the radioactive materials. We present a fully-automated microfluidic
      system based on sweeping gas membrane distillation to rapidly perform the
      concentration and formulation process. After detailed characterization of the
      system, we demonstrate fast and efficient concentration and formulation of
      several PET tracers, evaluate residual solvent content to establish the safety of
      the formulated tracers for injection, and show that the formulated tracer can be
      used for in vivo imaging.

PMID- 28443843
TI  - Atmospheric pressure soft ionization for gas chromatography with dielectric
      barrier discharge ionization-mass spectrometry (GC-DBDI-MS).
AB  - In this study, a gas chromatography (GC) system was interfaced to a high
      resolution Orbitrap mass spectrometer by means of an active capillary plasma
      ionization source, based on dielectric barrier discharge ionization (DBDI). This
      allowed highly efficient soft ionization of gas-phase, chromatographically
      resolved compounds at ambient pressure. Several pesticides and illicit drugs were
      analyzed, and the limits of detections (LODs) were as low as 30 pg mL-1 for the
      GC-DBDI-MS coupling (corresponding to 60 fg on-column sensitivity) and 30 fg mL-1
      for SPME-GC-DBDI-MS.

PMID- 28443844
TI  - Transformation of the ionic liquid [EMIM][B(CN)4] into anionic and neutral
      lanthanum tetracyanoborate coordination polymers by ionothermal reactions.
AB  - The lanthanum tetracyanoborate coordination polymers [EMIM]
      [LaNO3{B(CN)4}3(H2O)3] (EMIM = 1-ethyl-3-methylimidazolium) and
      [La(NO3)2[B(CN)4](H2O)4] mark first examples of Ln-tetracyanoborates that have
      been obtained in ionothermal syntheses without further solvents to influence e.g.
      viscosity. Thereby, the ionic liquid [EMIM][B(CN)4] is fully incorporated into
      product formation.

PMID- 28443845
TI  - Passive and active colloidal chemotaxis in a microfluidic channel: mesoscopic and
      stochastic models.
AB  - Chemotaxis is the response of a particle to a gradient in the chemical
      composition of the environment. While it was originally observed for biological
      organisms, it is of great interest in the context of synthetic active particles
      such as nanomotors. Experimental demonstration of chemotaxis for chemically
      powered colloidal nanomotors was reported in the literature in the context of
      chemo-attraction in a still fluid or in a microfluidic channel where the gradient
      is sustained by a specific inlet geometry. In this work, we use mesoscopic
      particle-based simulations of the colloid and solvent to demonstrate chemotaxis
      in a microfluidic channel. On the basis of this particle-based model, we evaluate
      the chemical concentration profiles in the presence of passive or chemically
      active colloids, compute the chemotactic force acting upon them and propose a
      stochastic model that rationalises our findings on colloidal chemotaxis. Our
      model is also able to explain the results of an earlier simulation work that uses
      a simpler geometry and to extend its interpretation.

PMID- 28443847
TI  - The impact of dietary sn-2 palmitic triacylglycerols in combination with
      docosahexaenoic acid or arachidonic acid on lipid metabolism and host faecal
      microbiota composition in Sprague Dawley rats.
AB  - Sn-2 palmitic acid triacylglycerols (sn2PA fat) and polyunsaturated fatty acids
      are thought to influence the metabolic status and intestinal bacterial population
      of the host. In this study, the impact of sn2PA fat in combination with DHA or
      ARA in the diet on lipid metabolism in the liver and faecal microbiota
      composition were investigated in rats fed diets containing sn2PA fat, 90% sn2PA
      fat + 10% DHA oil (wt%), or 90% sn2PA fat + 10% ARA oil (wt%). Tissue fatty acid
      composition was measured using gas chromatography (GC), whereas the faecal
      microbial composition was assessed using 16S rRNA high-throughput sequencing
      technology. In addition, faecal short-chain fatty acids (SCFA) were analyzed
      using ion chromatography. The results showed that sn2PA fat in combination with
      DHA or ARA significantly reduced liver triacylglyceride (TG) content compared
      with the sn2PA fat only group. Moreover, the supplementation with sn2PA fat in
      combination with DHA or ARA significantly promoted the growth of Lactobacillus in
      the feces at the genus level. On the other hand, the growth of the opportunistic
      pathogen Desulfovibrio was significantly inhibited by sn2PA fat in combination
      with ARA compared with the sn2PA fat group. In addition, sn2PA fat in combination
      with DHA or ARA significantly increased total SCFA concentration in the faeces,
      suggesting a beneficial effect on host intestinal health.

PMID- 28443846
TI  - On-chip enzymatic microbiofuel cell-powered integrated circuits.
AB  - A variety of diagnostic and therapeutic medical technologies rely on long term
      implantation of an electronic device to monitor or regulate a patient's
      condition. One proposed approach to powering these devices is to use a biofuel
      cell to convert the chemical energy from blood nutrients into electrical current
      to supply the electronics. We present here an enzymatic microbiofuel cell whose
      electrodes are directly integrated into a digital electronic circuit. Glucose
      oxidizing and oxygen reducing enzymes are immobilized on microelectrodes of an
      application specific integrated circuit (ASIC) using redox hydrogels to produce
      an enzymatic biofuel cell, capable of harvesting electrical power from just a
      single droplet of 5 mM glucose solution. Optimisation of the fuel cell voltage
      and power to match the requirements of the electronics allow self-powered
      operation of the on-board digital circuitry. This study represents a step towards
      implantable self-powered electronic devices that gather their energy from
      physiological fluids.

PMID- 28443848
TI  - Semiempirical modeling of electrochemical charge transfer.
AB  - Nanoelectrochemical experiments using detection based on tip enhanced Raman
      spectroscopy (TERS) show a broad distribution of single-molecule formal
      potentials E degrees ' for large pi-conjugated molecules; theoretical studies are
      needed to understand the origins of this distribution. In this paper, we present
      a theoretical approach to determine E degrees ' for electrochemical reactions
      involving a single molecule interacting with an electrode represented as a metal
      nanocluster and apply this method to the Ag20-pyridine system. The theory is
      based on the semiempirical INDO electronic structure approach, together with the
      COSMO solvation model and an approach for tuning the Fermi energy, in which the
      silver atomic orbital energies are varied until the ground singlet state of Ag20
      pyridine matches the lowest triplet energy, corresponding to electron transfer
      from the metal cluster to pyridine. Based on this theory, we find that the
      variation of E degrees ' with the structure of the Ag20-pyridine system is only
      weakly correlated with changes in either the ground-state interaction energy or
      the charge-transfer excited-state energies at zero applied potential, which shows
      the importance of calculations that include an applied potential in determining
      the variation of formal potential with geometry. Factors which determine E
      degrees ' include wavefunction overlap for geometries when pyridine is close to
      the surface, and electrostatics when the molecule-cluster separation is large.

PMID- 28443849
TI  - Specific single-molecule detection of glucose in a supramolecularly designed
      tunnel junction.
AB  - Scanning tunneling microscopy tips were functionalized with a boronic acid
      derivative. In combination with a similarly modified substrate, the molecular tip
      forms a supramolecular complex selectively with a glucose molecule. The
      conductance of the resulting single complex allows one to achieve the specific
      single-molecule detection of glucose.

PMID- 28443850
TI  - Selective adsorption of carbohydrates and glycoproteins via molecularly imprinted
      hydrogels: application to visible detection by a boronic acid monomer.
AB  - Selective adsorption of carbohydrates and glycoproteins was effectively achieved
      by molecularly imprinted hydrogels (MIHs) with a poly(ethylene glycol) (PEG)
      based crosslinker and 4-vinylphenylboronic acid. In addition, an MIH with a novel
      boronic acid monomer provided selective adsorption and enabled visible detection
      of fructose.

PMID- 28443851
TI  - Access to divergent benzo-heterocycles via a catalyst-dependent strategy in the
      controllable cyclization of o-alkynyl-N-methoxyl-benzamides.
AB  - A chemo- and regio-selectively controllable approach for construction of diverse
      benzo-heterocycles is established. A new strategy for using the ligand effect in
      gold catalysis to control the regioselectivity in the cyclization of o-alkynyl-N
      methoxyl-benzamide is successfully achieved. Meanwhile, the chemoselectivity
      between nitrogen and oxygen nucleophiles is precisely switched by gold and
      platinum catalysts.

PMID- 28443852
TI  - A biosensor based on self-clickable AIEgen: a signal amplification strategy for
      ultrasensitive immunoassays.
AB  - A signal amplified fluorogenic ELISA based on self-clickable fluorogens with
      aggregation-induced emission characteristics (AIEgen) as a substrate was
      developed for ultrasensitive immunoassay.

PMID- 28443853
TI  - Phage capsid protein-directed MnO2 nanosheets with peroxidase-like activity for
      spectrometric biosensing and evaluation of antioxidant behaviour.
AB  - Small molecular weight proteins (5.21 kDa) were used as bio-templates to
      synthesize MnO2 nanosheets (NSs). This work will open up a protein-directed
      avenue to synthesize 2D morphology. Further, the as-prepared MnO2 NSs showed
      intrinsic peroxidase-like activity and were then applied for glucose detection
      and evaluation of antioxidant behaviours of typical antioxidants.

PMID- 28443854
TI  - Infrared laser writing of MOFs.
AB  - An infrared (IR) laser machine is used for the synthesis of metal-organic
      frameworks (MOFs). Solutions containing metal ions and organic ligands are casted
      on glass substrates. MOF crystals are formed at the positions the IR laser
      irradiated, resulting in the patterning of MOFs.

PMID- 28443855
TI  - Dielectric functions and critical points of crystalline WS2 ultrathin films with
      tunable thickness.
AB  - Centimeter-scale WS2 ultrathin films were synthesized on sapphire substrates, and
      they showed highly oriented crystallographic growth along the c axis. Afterwards,
      the as-grown samples were systematically characterized using various detection
      methods. Reliable values of the roughness layer thickness and the film thickness
      were extracted using both atomic force microscopy (AFM) and spectroscopic
      ellipsometry (SE), and identified using Raman spectroscopy as well. The expansion
      and tensile strain along the [001] direction were discovered using X-ray
      diffraction (XRD) measurements. Accurate dielectric functions of WS2 films were
      derived from the point-by-point fitting results. The critical points (CPs) of
      WS2, which have not been reported so far, are precisely extracted from the
      standard critical point (SCP) model. Their origins are uniquely assigned to
      different interband electronic transitions in the Brillouin zone, including some
      novel optical structures above 3 eV, which were not investigated in earlier
      studies. In this work, it is found that dielectric functions are thickness
      dependent, while CPs have an opposite nature, and their intrinsic mechanisms are
      revealed. The as-obtained results can be expected to help people develop more
      extensive applications of WS2.

PMID- 28443856
TI  - A hypercrosslinking-induced self-assembly strategy for preparation of advanced
      hierarchical porous polymers with customizable functional components.
AB  - The fabrication of advanced hierarchical porous polymers with a unique 3D
      nanonetwork structure composed of functional core-microporous shell nanoparticles
      was reported based on the development of a simple and efficient hypercrosslinking
      induced self-assembly strategy.

PMID- 28443857
TI  - Adhesion contact deformation in nanobridge tests.
AB  - An accurate grasp of the mechanical properties, especially Young's moduli, of one
      dimensional nanomaterials plays a crucial role in the design and safe service of
      flexible electronic devices and implanted biomedical sensors. Nanobridge tests
      are widely used in the characterization of the mechanical properties of
      nanowires. In these tests, an atomic force microscope (AFM), functioning as a
      test machine, exerts a force to bend a nanowire suspended across a trench or a
      hole with the two ends fixed on a template or substrate. Adhesion contact
      deformation occurs inevitably during nanobridge testing between the AFM tip and
      the tested sample, thereby underestimating the Young's modulus of the tested
      nanowire and causing a pseudo-size effect in the determined Young's modulus. The
      present work systematically investigates the adhesion contact deformation in
      nanobridge tests and provides an analytical approach to evaluate the contact
      deformation and to determine the Young's modulus. To illustrate the developed
      methodology, AFM nanobridge tests were conducted on gold nanowires (180-340 nm
      wide, 3.6-5.1 MUm long and 90 nm thick). The results indicate that when the
      contact deformation was taken into consideration, the average Young's modulus
      increased by 4.63%. Guidelines for minimizing the impact of contact deformation
      in practical experiments are presented. Furthermore, the results provide insight
      into the probable causes of the variation in experimentally obtained size
      dependencies of Young's moduli of nanowires.

PMID- 28443858
TI  - Multi-state nonadiabatic deactivation mechanism of coumarin revealed by ab initio
      on-the-fly trajectory surface hopping dynamic simulation.
AB  - An on-the-fly trajectory surface hopping dynamic simulation has been performed
      for revealing the multi-state nonadiabatic deactivation mechanism of coumarin.
      The mechanism involves three adiabatic excited states, S3(pipi*Lb), S2(npi*,
      pipi*La) and S1(pipi*La, npi*), and the ground state S0 at the four state
      averaged complete active space self-consistent field, SA4-CASSCF(12,10)/6-31G*
      level of theory. Upon photoexcitation to the third excited state S3(pipi*Lb) in
      the Franck-Condon region, 80% sampling trajectories decay to the dark S2(npi*)
      state within an average of 5 fs via the conical intersection
      S3(pipi*Lb)/S2(npi*), while 20% decay to the S2(pipi*La) state within an average
      of 11 fs via the conical intersection S3(pipi*Lb)/S2(pipi*La). Then, sampling
      trajectories via S2(npi*)/S1(pipi*La) continue with ultrafast decay processes to
      give a final distribution of quantum yields as follows: 42% stay on the dark
      S1(npi*) state, 43.3% go back to the ground S0 state, 12% undergo a ring-opening
      reaction to the Z-form S0(Z) state, and 2.7% go to the E-form S0(E) state. The
      lifetimes of the excited states are estimated as follows: the S3 state is about
      12 fs on average, the S2 state is about 80 fs, and the S1 state has a fast
      component of about 160 fs and a slow component of 15 ps. The simulated ultrafast
      radiationless deactivation pathways of photoexcited coumarin immediately
      interpret the experimentally observed weak fluorescence emission.

PMID- 28443859
TI  - Adamantyl metal complexes: new routes to adamantyl anions and new
      transmetallations.
AB  - New routes to 1- and 2-adamantyl anion equivalents are described, starting from
      commercially available 1- and 2-adamantylzinc bromides and employing reducing
      metals (Mg; Li). Adamantylmagnesium bromides (both 1-AdMgBr and 2-AdMgBr) can
      reliably be produced via reaction of the corresponding adamantylzinc bromides
      with excess magnesium metal. Reactions of adamantylzinc bromides with
      stoichiometic lithium biphenylide or lithium 2,2'-bipyridylide afford the new
      diadamantylzinc species, 1-Ad2Zn and 2-Ad2Zn, isolable free of solvent and salt
      impurities. Addition of 2,2'-bipyridine (bipy) leads to the crystalline adducts 1
      Ad2Zn(bipy) and 2-Ad2Zn(bipy), which were structurally characterized. The
      resulting adamantyl anions were used in order to generate the first adamantyl
      complexes of mercury (1- and 2-Ad2Hg), gold (1- and 2-AdAu(PPh3), 1- and 2
      AdAu(PCy3)) and bismuth (2-Ad2BiBr), of which 1- and 2-Ad2Hg, 2-AdAu(PPh3), 2
      AdAu(PCy3), and 2-Ad2BiBr were isolated. These include the first structurally
      characterized unsupported 2-adamantyl metal complexes.

PMID- 28443860
TI  - Fabrication of large-area polymer microfilter membranes and their application for
      particle and cell enrichment.
AB  - A vacuum assisted UV micro-molding (VAUM) process is proposed for the fabrication
      of freestanding and defect-free polymer membranes based on a UV-curable
      methacrylate polymer (MD 700). VAUM is a highly flexible and powerful method for
      fabricating low cost, robust, large-area membranes over 9 * 9 cm2 with pore sizes
      from 8 to 20 MUm in diameter, 20 to 100 MUm in thickness, high aspect ratio (the
      thickness of the polymer over the diameter of the hole is up to 15 : 1), high
      porosity, and a wide variety of geometrical characteristics. The fabricated
      freestanding membranes are flexible while mechanically robust enough for post
      manipulation and handling, which allows them to be cut and integrated as a
      plastic cartridge onto thermoplastic 3D microfluidic devices with single or
      double filtration stages. Very high particle capture efficiencies (~98%) have
      been demonstrated in the microfluidic devices integrated with polymer membranes,
      even when the size of the beads is very close to the size of the pores of the
      microfilter. About 85% of the capture efficiency has been achieved in cancer cell
      trapping experiments, in which a breast cancer cell line (MDA-MB-231) spiked with
      phosphate-buffered saline buffer when the pore size of the filter is 8 MUm and
      the device is operated at a flow rate of 0.1 mL min-1.

PMID- 28443861
TI  - KVPO4F and KVOPO4 toward 4 volt-class potassium-ion batteries.
AB  - Structurally identical KVPO4F and KVOPO4 are evaluated as positive electrode
      materials for non-aqueous potassium-ion batteries. KVPO4F and KVOPO4 show highly
      reversible potassium extraction/insertion with discharge capacities of ca. 92 mA
      h g-1 and ca. 84 mA h g-1, respectively, and their average discharge voltage
      reaches above 4.0 V with 1 M KPF6 EC/PC electrolyte at 2.0-5.0 V. Despite the
      extraction of large potassium-ions, their lattice volume shrinkages after
      charging to 5.0 V are 5.8% for KVPO4F and 3.3% for KVOPO4, leading to stable
      cycle performance. This is the first report to confirm the charge/discharge
      behaviours of vanadium phosphate electrodes in 4 V-class K cells.

PMID- 28443862
TI  - A small bandgap semiconductor, p-type MnV2O6, active for photocatalytic hydrogen
      and oxygen production.
AB  - Extensive research has been conducted with the goal to find a single bandgap
      material that can absorb visible light and efficiently drive the catalysis of
      water to both hydrogen and oxygen. The p-type MnV2O6 (C2/m, Z = 2, a = 9.289 A, b
      = 3.535 A, and c = 6.763 A, beta = 112.64 degrees ), synthesized via solid-state
      techniques, was investigated for its potential use in the visible-light
      photocatalysis of water. Mott-Schottky analysis was used to experimentally
      determine the energetic positions of the valence and conduction bands as +0.985 V
      and -0.464 V, respectively, at pH 5.68 vs. RHE. These are found to be suitable
      potentials to drive the reduction and oxidation of water under irradiation. The
      bandgap transitions, probed using spin-polarized density functional calculations,
      consist of the excitation of electrons from the half-filled Mn 3d5 orbitals to
      the empty V 3d0 orbitals. Both hydrogen and oxygen gas were observed as products
      during suspended-particle photocatalysis experiments under visible-light
      irradiation. The rate and total moles of gas produced were found to increase with
      the reaction temperature. As the temperature was raised from 30  degrees C to 37 
      degrees C and 44  degrees C, the moles of hydrogen produced over 6 hours
      increased by ~1.5 and ~2.5 times. Only oxygen is produced in pure water, showing
      that methanol is needed to drive hydrogen production.

PMID- 28443864
TI  - Planar-chiral ferrocenylphosphine-borane complexes featuring agostic-type B-HE (E
      = Hg, Sn) interactions.
AB  - The synthesis of ferrocenylphosphine-borane adducts 1,2-fc(E)(PPh2.BH3) (E =
      SnR2R', HgX; 1,2-fc = 1,2-ferrocenediyl) that are substituted with organotin or
      organomercury Lewis acid moieties in ortho-position is presented. Several
      compounds that feature two ferrocenylphosphine-borane moieties bridged by Sn or
      Hg are also introduced. The products are fully characterized by multinuclear NMR
      spectroscopy, high-resolution MALDI-TOF mass spectrometry and elemental analysis.
      The attachment of the Lewis acid substituent to the same Cp ring of the ferrocene
      results in planar-chirality and the close proximity between the boron hydride
      group and the Lewis acid is expected to allow for agostic-type B-HE (E = Sn, Hg)
      interactions. Structural investigations by X-ray diffraction reveal a short B-HSn
      contact of 2.755(4) A for 1,2-fc(SnMe2Cl)(PPh2.BH3), which is only the second
      reported example of such a short agostic-type contact involving a coordinatively
      saturated tin(iv) center. In contrast, for the tetraorganotin derivatives 1,2
      fc(SnMe3)(PPh2.BH3) and [1,2-fc(PPh2)](MU-SnMe2)[1,2-fc(PPh2.BH3)], in which the
      Lewis acidity of the tin atom is weaker than in 1,2-fc(SnMe2Cl)(PPh2.BH3), the B
      HSn distances are much longer but still within the sum of the van der Waals radii
      of Sn and H (?vdW = 3.27 A). The chloromercury-substituted ferrocenylphosphine
      borane 1,2-fc(HgCl)(PPh2.BH3) shows a similarly short B-HHg contact of 2.615(5) A
      (?vdW = 3.15 A). Inspection of the extended structure of 1,2-fc(HgCl)(PPh2.BH3)
      reveals that the Lewis acidic mercury atom is also involved in intermolecular
      HgCl interactions with a neighboring molecule. An analysis of 31P and 11B NMR
      data reveals a correlation between the chemical shifts and the Lewis acidity of
      the adjacent organotin/mercury substituent. Structure optimization of 1,2
      fc(SnMe3)(PPh2.BH3) and 1,2-fc(SnMe2Cl)(PPh2.BH3) by density functional theory
      (DFT) indicates B-HSn contacts respectively of 3.129 and 2.631 A that are close
      to the experimental values. Natural bond orbitals (NBO) and atom in molecules
      (AIM) analyses reveals a B-H->Sn donor-acceptor interaction energy of 5.46 kcal
      mol-1 and a B-HSn bond path for the chlorodimethyltin-substituted derivative with
      a modest electron density rho(r) of 0.0082 a.u. and a positive Laplacian at the
      bond critical point.

PMID- 28443863
TI  - [FeFe] Hydrogenase active site model chemistry in a UiO-66 metal-organic
      framework.
AB  - The reactivity of [Fe2(dcbdt)(CO)6] (1) confined in a UiO-66(Zr) metal-organic
      framework towards CO ligand substitutions with phosphines of different sizes was
      investigated. The reaction with smaller phosphines (PX3, X = Me, Et) is more
      selective compared to analogous reactions in homogenous solution phase, and two
      CO ligands at up to 80% of all [FeFe] sites in UiO-66-1 are replaced. The
      produced [Fe2(dcbdt)(CO)4(PX3)2] complexes in the UiO-66 matrix behave like
      typical [FeFe] hydrogenase active site model complexes, are reduced at more
      cathodic potentials than their hexacarbonyl analogues, and form bridging hydrides
      under acidic conditions.

PMID- 28443865
TI  - Simultaneous use of MOFs MIL-101(Cr) and ZIF-11 in thin film nanocomposite
      membranes for organic solvent nanofiltration.
AB  - The MOFs Cr carboxylate MIL-101(Cr) and Zn imidazolate ZIF-11 have different
      chemical and textural properties. These properties have been combined to prepare
      thin film nanocomposite (TFN) membranes for organic solvent nanofiltration (OSN)
      with the two MOFs simultaneously embedded in the same membrane. The TFN membrane
      containing only ZIF-11 permeated faster than that with only MIL-101(Cr) when
      filtering sunset yellow (SY) (4.9 L m-2 h-1 bar-1) and acridine orange (AO) (3.2
      L m-2 h-1 bar-1), although MIL-101(Cr) alone gave rise in both cases to better
      rejections (above 90%). The combination of the two MOFs led to a versatile TFN
      membrane that showed an intermediate performance that improved the rejections
      given by the TFN membrane synthesized with ZIF-11 and the permeances
      corresponding to the TFN membrane synthesized with MIL-101(Cr). The effect of the
      temperature on the TFN membranes designed for this work has also been studied,
      obtaining apparent activation energies of 13.2 +/- 2.1 and 8.3 +/- 1.1 kJ mol-1
      for the OSN of pure methanol and SY-methanol, respectively.

PMID- 28443866
TI  - In situ investigation of degradation at organometal halide perovskite surfaces by
      X-ray photoelectron spectroscopy at realistic water vapour pressure.
AB  - Near-ambient-pressure X-ray photoelectron spectroscopy enables the study of the
      reaction of in situ-prepared methylammonium lead iodide (MAPI) perovskite at
      realistic water vapour pressures for the first time. We show that MAPI decomposes
      directly to PbI2, HI and NH3 without formation of methylammonium iodide, allowing
      us to distinguish between alternative mechanisms for the atmospheric degradation
      reaction.

PMID- 28443867
TI  - Application of the boron center for the design of a covalently bonded closely
      spaced triad of porphyrin-fullerene mediated by dipyrromethane.
AB  - Two novel triads had been designed through covalent bond connection of the boron
      dipyrromethane (BODIPY), free base porphyrin (H2P) or zinc(ii) porphyrin (ZnP)
      and N-methyl-2-phenyl-3,4-fulleropyrrolidine (C60) mediated by BODIPY. This
      closely spaced triad arrangement where porphyrin and fullerene are placed apart
      is anticipated to stabilize charge separation by separating the two radicals from
      each other. Two model polyads were synthesized with BODIPY and H2P or ZnP to
      investigate interaction between the two chromophores. Photo-excitation of the
      BODIPY triggered an efficient singlet energy transfer where the rates are found
      to be ~1010-1011 s-1. For triads with C60 fast electron transfer was confirmed by
      the detection of the C60- signature from femtosecond transient absorption (fs-TA)
      in ~0.4-3 ps. The charge recombination is estimated to be in the nanosecond
      window. This indicates the convenience of this arrangement for stabilizing the
      charge-separated state.

PMID- 28443868
TI  - Selective S-arylation of 2-oxazolidinethiones and selective N-arylation of 2
      benzoxazolinones/2-benzimidazolinones.
AB  - There exist three possible patterns for the reaction of cyclic 2
      oxazolidinethione and 2-benzoxazolidinethione with arynes, namely (a) S
      arylation, (b) N-arylation, and (c) aryne insertion into the thiocarbonyl group
      (C[double bond, length as m-dash]S). Our studies demonstrate that S-arylation
      wins out affording S-aryl dihydrooxazoles. In contrast, for related reactions of
      cyclic 2-benzoxazolinone and 2-benzimidazolinone with arynes, it is found that N
      arylation outcompetes O-arylation and aryne insertion into the C[double bond,
      length as m-dash]O group to give N-aryl 2-benzoxazolinones and N-aryl 2
      benzimidazolinones.

PMID- 28443869
TI  - A chiral member of the family of organic hexameric cages.
AB  - A cubic nanocage (O symmetry) that exhibits inherent chirality and has a
      covalent, rigid skeleton with molecule-sized entrance portals was obtained by
      means of dynamic covalent chemistry using a reaction between aldehyde
      functionalized resorcin[4]arene and hydrazine.

PMID- 28443870
TI  - Operando X-ray spectroscopic observations of modulations of local atomic and
      electronic structures of color switching smart film.
AB  - Smart windows, which change color in response to external stimuli, are
      extensively studied owing to their potential technological applications in
      sensors and their ability to reduce the energy consumed by buildings. Most
      related studies focus on the optical properties of smart color switching films
      that can control the transmission of light and that of heat independently. This
      study examines the vanadium pentoxide thin film as a model system of a color
      switchable window. A gasochromic thin film of V2O5 is fabricated using sol-gel
      spin coating. In operando soft X-ray absorption spectroscopy (XAS) at the V L
      edge is used to determine the evolutions of the electronic and atomic structures
      of V2O5 thin film under gasochromic color switching. Analysis of the V K-edge
      with respect to crystalline structural symmetry and valence requires many
      reference samples, whereas the V L-edge, which involves V 3d orbitals of various
      symmetries, can provide information about the atomic/electronic structures
      without many reference samples. A new gas reaction in situ cell was developed to
      collect the total-electron-yield XAS. The total-electron-yield signal can provide
      more accurate information about atomic and electronic structures than can the
      fluorescence-yield signal, which typically exerts a saturation effect. Analytical
      results reveal that the gasochromic reaction changes the charge state and causes
      a local atomic structural deformation of the film. The suggestion has been made
      that in the reaction, the central vanadium atom within the octahedron moves
      closer to the basal plane such that the apical V-O bond becomes more symmetrical
      than the film before gasochromic coloration. Unlike the cell that is used for
      hard XAS, and for which only cation sites can be studied, this in situ gas cell
      enables the real-time studies of atomic/electronic structures at gas-solid
      interfaces from viewpoints of both cation and anion sites.

PMID- 28443871
TI  - Rapid detection of nicotine from breath using desorption ionisation on porous
      silicon.
AB  - Desorption ionisation on porous silicon (DIOS) was used for the detection of
      nicotine from exhaled breath. This result represents proof-of-principle of the
      ability of DIOS to detect small molecular analytes in breath including biomarkers
      and illicit drugs.

PMID- 28443872
TI  - Synthesis of novel bis(Triol)-functionalized Anderson clusters serving as
      potential synthons for forming organic-inorganic hybrid chains.
AB  - Three novel bis(Triol)-functionalized Anderson cluster derivatives (POM-L-POM,
      POM-L, L-POM-L) were efficiently synthesized, which manifest interesting self
      assembly and synergistic effects. They provided strong support in synthons,
      applications in syntheses and properties for designing organic-inorganic hybrid
      chains.

PMID- 28443873
TI  - A neutral halogen bonding macrocyclic anion receptor based on a
      pseudocyclopeptide with three 5-iodo-1,2,3-triazole subunits.
AB  - The converging arrangement of iodine atoms along its confined cavity causes a
      cyclic pseudopeptide with three 5-iodo-1,2,3-triazole subunits to interact with
      halides, in particular with chloride, in 2.5 vol% water/DMSO.

PMID- 28443874
TI  - Inertial migration and axial control of deformable capsules.
AB  - The mechanical deformability of single cells is an important indicator for
      various diseases such as cancer, blood diseases and inflammation. Lab-on-a-chip
      devices allow to separate such cells from healthy cells using hydrodynamic
      forces. We perform hydrodynamic simulations based on the lattice-Boltzmann method
      and study the behavior of an elastic capsule in a microfluidic channel flow in
      the inertial regime. While inertial lift forces drive the capsule away from the
      channel center, its deformability favors migration in the opposite direction.
      Balancing both migration mechanisms, a deformable capsule assembles at a specific
      equilibrium distance depending on its size and deformability. We find that this
      equilibrium distance is nearly independent of the channel Reynolds number and
      falls on a single master curve when plotted versus the Laplace number. We
      identify a similar master curve for varying particle radius. In contrast, the
      actual deformation of a capsule strongly depends on the Reynolds number. The lift
      force profiles behave in a similar manner as those for rigid particles. Using the
      Saffman effect, the capsule's equilibrium position can be controlled by an
      external force along the channel axis. While rigid particles move to the center
      when slowed down, very soft capsules show the opposite behavior. Interestingly,
      for a specific control force particles are focused on the same equilibrium
      position independent of their deformability.

PMID- 28443875
TI  - Investigating anomalous thermal expansion of copper halides by inelastic neutron
      scattering and ab initio phonon calculations.
AB  - We investigate the detailed lattice dynamics of copper halides, CuX (X = Cl, Br,
      and I), using neutron inelastic scattering measurements and ab initio
      calculations aimed at a comparative study of their thermal expansion behavior. We
      identify the low energy phonons which soften with pressure and are responsible
      for negative thermal expansion. The eigenvector analysis of these modes suggests
      that softening of the transverse-acoustic modes would lead to NTE in these
      compounds. The calculations are in very good agreement with our measurements of
      phonon spectra and thermal expansion behavior as reported in the literature. Our
      calculations at high pressure further reveal that a large difference in negative
      thermal expansion behavior in these compounds is associated with the difference
      in the unit cell volume.

PMID- 28443876
TI  - Alcohol-mediated direct dithioacetalization of alkynes with 2-chloro-1,3-dithiane
      for the synthesis of Markovnikov dithianes.
AB  - An alcohol-mediated dithioacetalization process that gains direct access to the
      corresponding Markovnikov-selective 1,3-dithianes using unactivated alkynes and
      nonthiolic/odorless 2-chloro-1,3-dithiane in a highly efficient manner has been
      developed. This methodology has the advantage of having mild reaction conditions,
      and the dithioacetalization process gives good to excellent yields with high
      Markovnikov-selectivity.

PMID- 28443877
TI  - NMR of molecular endofullerenes dissolved in a nematic liquid crystal.
AB  - We report the NMR of the molecular endofullerenes H2@C60, H2O@C60 and HF@C60
      dissolved in the nematic liquid crystal N-(4-methoxybenzylidene)-4-butylaniline
      (MBBA). The 1H NMR lines of H2 and H2O display a doublet splitting due to
      residual dipole-dipole coupling. The dipolar splitting depends on temperature in
      the nematic phase and vanishes above the nematic-isotropic phase transition. The
      19F spectrum of HF@C60 dissolved in MBBA displays a doublet splitting in the
      nematic phase, with contributions from the 1H-19F dipole-dipole coupling and J
      coupling. The phenomena are analyzed using a model in which the fullerene cages
      acquire a geometrical distortion, either through interaction with the liquid
      crystal environment, or through their interaction with the endohedral molecules.
      The distorted cages become partially oriented with respect to the liquid crystal
      director, and the endohedral molecules become partially oriented with respect to
      the distorted cages.

PMID- 28443878
TI  - Influence of high energy electron irradiation on the network structure of gelatin
      hydrogels as investigated by small-angle X-ray scattering (SAXS).
AB  - The impact of high energy crosslinking on the network structure of gelatin
      hydrogels was investigated in comparison to physically entangled gels by small
      angle X-ray scattering (SAXS). Physically entangled gelatin of increasing
      concentration exhibited a nearly constant correlation length of several
      nanometers. These gels had scattering behavior close to that of polymer coils
      swollen in a good solvent, as evidenced by the Porod exponent of 1.8. The mass
      fractal dimension decreased towards 1, indicating increased formation of
      semiflexible gelatin triple helices and rod-like structures as a function of the
      gelatin concentration. In contrast, electron irradiation lead to a decrease in
      the correlation length at doses above 20 kGy. Covalent crosslinking induced by
      electron irradiation lead to increased branching and formation of globular
      structures, as observed by a steady increase of both the Porod exponent and mass
      fractal dimension. Furthermore, the network mesh size systematically decreased
      from approximately 45 nm to under 20 nm with both additional physical and
      chemical crosslinking. These mesh sizes as obtained by SAXS were used to estimate
      the network shear modulus using several polymer models and were compared to
      macroscopic rheology measurements. Finally, SEM images of freeze-dried samples
      revealed changes in the microstructure of the irradiated hydrogels. Overall,
      fundamental differences in the network structures stemming from the crosslinking
      method were observed across a wide range of length scales.

PMID- 28443880
TI  - Asymmetric synthesis of ent-fragransin C1.
AB  - The first asymmetric synthesis of ent-fragransin C1 was reported. The key step
      involves an intramolecular C-O bond formation (furan ring formation) via
      chemoselective generation of the benzylic carbocation leading to the 2,3-anti-3,4
      syn-4,5-anti-tetrahydrofuran moiety as a single diastereomer in good yield. Our
      synthesis confirms that ent-fragransin C1 possesses 2R,3R,4S,5S configurations.

PMID- 28443879
TI  - Pyrazolates advance cerium chemistry: a CeIII/CeIV redox equilibrium with
      benzoquinone.
AB  - Two stable cerium(iv) 3,5-dialkylpyrazolate complexes are presented, namely
      dimeric [Ce(Me2pz)4]2 (Me2pz = 3,5-dimethylpyrazolate) and monomeric Ce(tBu2pz)4
      (tBu2pz = 3,5-di-tert-butylpyrazolate) along with their trivalent counterparts
      [Ce(Me2pz)3] and [Ce(tBu2pz)3]2. All complexes were obtained from protonolysis
      reactions employing the silylamide precursors Ce[N(SiHMe2)2]4 and Ce[N(SiMe3)2]3.
      Treatment of homoleptic CeIV and CeIII Me2pz complexes with 1,4-hydroquinone
      (H2hq) or 1,4-benzoquinone (bq), respectively, ultimately gave the same
      trimetallic CeIII species via a cerium redox equilibrium. The CeIII complex
      Ce3(Me2pz)5(pchd)2(L) (pchd = 1,4-bis(3,5-dimethylpyrazol-1-yl)cyclohex-2,5-diene
      1,4-diolato; L = Me2pzH or (thf)2) results from a di-1,4-pyrazolyl attack on pre
      coordinated bq. The reduction of bq by [Ce(Me2pz)3(thf)]2, and re-oxidation by
      the resulting CeIV species was supported by UV-vis spectroscopic investigations.
      Comparisons with the redox-innocent complexes [Ln(Me2pz)3(thf)]2 (Ln = La and Pr)
      revealed far less selective reactions with bq, giving hexametallic and
      octametallic rare-earth metal side products containing 2-Me2pz substituted hq
      ligands.

PMID- 28443882
TI  - Regioselective 1,2-addition of allenamides with N-haloimides: synthesis of 2-halo
      allylic aminal derivatives.
AB  - A strategy for the synthesis of 2-halo allylic aminal derivatives through
      regioselective 1,2-addition of allenamides with N-haloimides is presented. This
      reaction was conducted under very mild conditions and gave up to 99% yield.
      Moreover, the obtained halides allow functional group diversification by
      palladium-catalyzed coupling reactions, which could act as potential
      intermediates for the synthesis of valuable compounds.

PMID- 28443881
TI  - Identification of the smallest peptide with a zwitterion as the global minimum: a
      first-principles study on arginine-containing peptides.
AB  - Zwitterions are believed to play an important role in determining the structures,
      properties and functions of peptides and proteins. However, the smallest peptide
      with a zwitterionic structure as the global minimum in the gas phase is still not
      yet identified. In this study, an effective step-by-step strategy has been used
      to characterize the stable conformers of arginine-containing peptides
      arginylalanine (ArgAla) and arginylserine (ArgSer). Energy calculations at the
      DSD-PBEP86-D3BJ/aug-cc-pVTZ level and further extrapolation to the complete basis
      set (CBS) limit have confirmed, for the first time, that ArgSer appears to be a
      promising candidate as the smallest peptide with a zwitterionic global minimum
      structure. First-principles simulations have been performed for near-edge X-ray
      absorption fine-structure (NEXAFS) spectra and X-ray photoelectron spectra (XPS)
      at C, N and O K-edges, as well as for infrared (IR) spectra of these arginine
      containing peptides. Notable spectral differences were found which enable the
      unambiguous identification of different neutral forms in future experiments. Our
      study thus provides valuable insights into the structural stability of
      zwitterions with the increase of molecular size and illustrates the competition
      between the canonical and zwitterionic isomers.

PMID- 28443884
TI  - Monolithic porous magnesium silicide.
AB  - Macroporous magnesium silicide monoliths were successfully prepared by a two-step
      synthesis procedure. The reaction of gaseous magnesium vapor with macro
      /mesoporous silicon, which was generated from hierarchically organized meso
      /macroporous silica by a magnesiothermic reduction reaction, resulted in
      monolithic magnesium silicide with a cellular, open macroporous structure. By
      adjusting the reaction conditions, such as experimental set-up, temperature and
      time, challenges namely loss of porosity or phase purity of Mg2Si were addressed
      and monolithic magnesium silicide with a cellular network builtup was obtained.

PMID- 28443883
TI  - An aza-BODIPY based near-infrared fluorescent probe for sensitive discrimination
      of cysteine/homocysteine and glutathione in living cells.
AB  - Discriminative detection of glutathione (GSH) from cysteine/homocysteine
      (Cys/Hcy) is achieved through two emission channel analysis using a stable,
      highly sensitive, and selective near-infrared fluorescent probe that bears 7
      nitrobenzo-2-oxa-1,3-diazole and aza-BODIPY units. The probe was successfully
      applied for simultaneous determination of GSH and Cys/Hcy in living cells.

PMID- 28443885
TI  - Atomistic modeling to investigate the favored composition for metallic glass
      formation in the Ca-Mg-Ni ternary system.
AB  - A realistic interatomic potential was first constructed for the Ca-Mg-Ni system
      and then applied to Monte Carlo simulations to predict the favored composition
      for metallic glass formation in the ternary system. The simulations not only
      predict a hexagonal composition region, within which the Ca-Mg-Ni metallic glass
      formation is energetically favored, but also pinpoint an optimized sub-region
      within which the amorphization driving force, i.e. the energy difference between
      the solid solution and disordered phase, is larger than that outside. The
      simulations further reveal that the physical origin of glass formation is the
      solid solution collapsing when the solute atom exceeds the critical solid
      solubility. Further structural analysis indicates that the pentagonal bi-pyramids
      dominate in the optimized sub-region. The large atomic size difference between
      Ca, Mg and Ni extends the short-range landscape and facilitates the development
      of a hybridized packing model in the medium-range, and eventually enhancing the
      glass formation in the system. The predictions are well supported by the
      experimental observations reported so far, and could be of help for designing the
      ternary glass formation.

PMID- 28443886
TI  - Supramolecular chemistry anniversary.

PMID- 28443887
TI  - Metal ion-induced supramolecular pKa tuning and fluorescence regeneration of a p
      sulfonatocalixarene encapsulated neutral red dye.
AB  - The host-guest interactions and the consequent modulation in the prototropic
      equilibrium of a phenazine dye, neutral red, with p-sulfonatocalix[4]arene (SCX4)
      and p-sulfonatocalix[6]arene (SCX6) macrocyclic hosts have been investigated.
      Both the neutral (NR) and cationic (NRH+) forms of dyes formed inclusion
      complexes with SCX6, with a larger binding constant for the latter (K = 8.6 * 105
      M-1versus 4.8 * 103 M-1) due to the cation receptor behavior of the calixarenes.
      The distinct differences in the binding constant of NR and NRH+ provided a finite
      tuning of pKa between 6.5 and 8.8, through a competitive binding with metal ions.
      Importantly, the fluorescence quenching observed in the SCX-neutral red
      interactions stands in contrast to the fluorescence enhancement observed with
      other macrocyclic hosts, such as beta-cyclodextrin and cucurbit[7]uril. This is
      due to the unique portal stacking interaction of NRH+ with the SCXs, compared to
      the axial inclusion geometry documented for the other macrocycles. The electron
      transfer from the SCX to the neutral red dye is adjudged to be the effective
      excited-state relaxation pathway leading to fluorescence quenching. In
      combination with the metal-ion induced fluorescence regeneration and tuning the
      pKa value, the SCX-neutral red system finds potential applications in drug
      delivery, photodynamic therapy, catalysis, and sensor applications.

PMID- 28443888
TI  - Sugar-peptidic bond interactions: spectroscopic characterization of a model
      system.
AB  - Sugars are small carbohydrates which play numerous roles in living organisms such
      as storage of energy or as structural components. Modifications of specific sites
      within the glycan chain can modulate a carbohydrate's overall biological function
      as it happens with nucleic acids and proteins. Hence, identifying discrete
      carbohydrate modifications and understanding their biological effects is
      essential. A study of such processes requires of a deep knowledge of the
      interaction mechanism at the molecular level. Here, we use a combination of laser
      spectroscopy in jets and quantum mechanical calculations to characterize the
      interaction between phenyl-beta-d-glucopyranoside and N-methylacetamide as a
      model to understand the interaction between a sugar and a peptide bond. The most
      stable structure of the molecular aggregate shows that the main interaction
      between the peptide fragment and the sugar proceeds via a C[double bond, length
      as m-dash]OH-O2 hydrogen bond. A second conformer was also found, in which the
      peptide establishes a C[double bond, length as m-dash]OH-O6 hydrogen bond with
      the hydroxymethyl substituent of the sugar unit. All the conformers present an
      additional interaction point with the aromatic ring. This particular preference
      of the peptide for the hydroxyl close to the aromatic ring could explain why
      glycogenin uses tyrosine in order to convert glucose into glycogen by exposing
      the O4H hydroxyl group for the other glucoses for the polymerization to take
      place.

PMID- 28443889
TI  - The passivating effect of cadmium in PbS/CdS colloidal quantum dots probed by nm
      scale depth profiling.
AB  - Achieving control of the surface chemistry of colloidal quantum dots (CQDs) is
      essential to fully exploit their properties in solar cells, but direct
      measurement of the chemistry and electronic structure in the outermost atomic
      layers is challenging. Here we probe the surface oxidation and passivation of
      cation-exchanged PbS/CdS core/shell CQDs with sub nm-scale precision using
      synchrotron-radiation-excited depth-profiling photoemission. We investigate the
      surface composition of the topmost 1-2.5 nm of the CQDs as a function of depth,
      for CQDs of varying CdS shell thickness, and examine how the surface changes
      after prolonged air exposure. We demonstrate that the Cd is localized at the
      surface of the CQDs. The surface-localized products of oxidation are identified,
      and the extent of oxidation quantified. We show that oxidised sulfur species are
      progressively eliminated as Cd replaces Pb at the surface. A sub-monolayer
      surface 'decoration' of Cd is found to be effective in passivating the CQDs. We
      show that the measured energy-level alignments at PbS/CdS colloidal quantum dot
      surfaces differ from those expected on the basis of bulk band offsets, and are
      strongly affected by the oxidation products. We develop a model for the
      passivating action of Cd. The optimum shell thickness (of around 0.1 nm,
      previously found to give maximised power conversion efficiency in PbS/CdS solar
      cells) is found to correspond to a trade-off between the rate of oxidation and
      the introduction of a surface barrier to charge transport.

PMID- 28443890
TI  - The characteristic landscape of lncRNAs classified by RBP-lncRNA interactions
      across 10 cancers.
AB  - RNA-binding proteins (RBPs) are key regulators of gene expression. Some long non
      coding RNAs (lncRNAs) affect gene expression by interacting with RBPs. However,
      whether this influences the biological characteristics of lncRNAs in diseases
      still remains unknown. Here, we classify lncRNAs into two categories, using the
      interaction information between lncRNAs and RBPs: the lncRNAs that interact with
      RBPs (Rlncs) and the lncRNAs that do not interact with RBPs (NRlncs). Then we
      systematically analyze the basic attributes and functions of the two categories
      of lncRNAs across 10 cancers. By comparing the two categories, we find that the
      attributes of Rlncs are significantly higher than those of NRlncs in different
      aspects such as expression level, protein-coding potential, and evolutionary
      conservation. Furthermore, functional enrichment analysis reveals that the two
      categories of lncRNAs are involved in different functions and biological
      pathways. Finally, the prognostic analysis results suggest that the two
      categories of lncRNAs affect the overall survival of patients through
      participating in different functions. Our systematic characterization of Rlncs
      and NRlncs provides a new perspective for understanding the role of lncRNAs, and
      improves knowledge of cancer biology.

PMID- 28443891
TI  - [3,3]-Sigmatropic rearrangement of allenic alcohols: stereoselective synthesis of
      1,3-diene-2-ol sulfonates.
AB  - An efficient synthetic pathway to 1,3-diene-2-ol sulfonates involving the [3,3]
      sigmatropic rearrangement of allenic alcohols with sulfonic acids under mild
      reaction conditions is described. These products can easily undergo reduction or
      transition-metal catalyzed cross-coupling reactions to yield a series of
      stereodefined multisubstituted 1,3-dienes.

PMID- 28443892
TI  - Near-infrared fluorescent dyes with large Stokes shifts: light generation in
      BODIPYs undergoing excited state intramolecular proton transfer.
AB  - Novel BODIPYs undergoing excited state intramolecular proton transfer are
      reported. The molecules afford NIR emission with a large Stokes shift and possess
      a free hydroxyl unit that is easy to functionalize, allowing the dyes to be
      exploited as a valuable scaffold in probe design.

PMID- 28443893
TI  - TRAIL-NP hybrids for cancer therapy: a review.
AB  - Cancer is a worldwide health problem. It is now considered as a leading cause of
      morbidity and mortality in developed countries. In the last few decades,
      considerable progress has been made in anti-cancer therapies, allowing the cure
      of patients suffering from this disease, or at least helping to prolong their
      lives. Several cancers, such as those of the lung and pancreas, are still
      devastating in the absence of therapeutic options. In the early 90s, TRAIL (Tumor
      Necrosis Factor-related apoptosis-inducing ligand), a cytokine belonging to the
      TNF superfamily, attracted major interest in oncology owing to its selective anti
      tumor properties. Clinical trials using soluble TRAIL or antibodies targeting the
      two main agonist receptors (TRAIL-R1 and TRAIL-R2) have, however, failed to
      demonstrate their efficacy in the clinic. TRAIL is expressed on the surface of
      natural killer or CD8+ T activated cells and contributes to tumor surveillance.
      Nanoparticles functionalized with TRAIL mimic membrane-TRAIL and exhibit stronger
      antitumoral properties than soluble TRAIL or TRAIL receptor agonist antibodies.
      This review provides an update on the association and the use of nanoparticles
      associated with TRAIL for cancer therapy.

PMID- 28443894
TI  - Taste and smell in aquatic and terrestrial environments.
AB  - Covering: up to 2017The review summarizes results up to 2017 on chemosensory cues
      occurring in both aquatic and terrestrial environments. The chemicals are grouped
      by their physicochemical properties to compare their potential mobility in the
      different media. In contrast to what is widely asserted in the literature, the
      report emphasizes that living organisms encounter and sense molecules of various
      degrees of solubility and volatility both on land and in aquatic environments.
      The picture that emerges from the review suggests a substantial revision of the
      traditional definitions of the chemical senses based on their spatial range,
      which is currently orienting the literature on chemosensory signaling, in favor
      of a new vision based on the natural products that are the actual mediators of
      the chemosensory perceptions. According to this perspective, natural product
      chemistry is a powerful tool with which to explore the evolutionary history of
      the chemical senses.

PMID- 28443895
TI  - Diamondoid-structured polymolybdate-based metal-organic frameworks as high
      capacity anodes for lithium-ion batteries.
AB  - Two novel isostructural polyoxometalate (POM)-based metal-organic frameworks
      (MOFs) with diamond topology, NENU-506 and NENU-507, were hydrothermally
      synthesized. They not only combine the advantages of both POMs and MOFs, but also
      show excellent chemical and thermal stability. Notably, NENU-507 exhibited a high
      reversible capacity of 640 mA h g-1 after 100 cycles when applied as an anode
      material in lithium-ion batteries.

PMID- 28443896
TI  - An MSN-PEG-IP drug delivery system and IL13Ralpha2 as targeted therapy for
      glioma.
AB  - A combination of gene therapy and chemotherapy has recently received interest as
      a targeted therapy for glioma. A mesoporous silica nanoparticle (MSN)-based
      vehicle coated with IL13Ralpha2-targeted peptide (IP) using polyethylene glycol
      (PEG), MSN-PEG-IP (MPI), was constructed and confirmed as a potential glioma
      targeted drug delivery system in vitro. In this work, tissue microarray (TMA)
      results revealed that IL13Ralpha2 was over-expressed in human glioma tissues and
      that high expression of IL13Ralpha2 in patients was associated with poor
      survival. Doxorubicin (DOX)-loaded MPI (MPI/D) crossed the blood-brain barrier,
      specifically targeting glioma cells and significantly enhancing the cellular
      uptake of DOX in glioma cells compared with MSN/DOX (M/D) and MSN-PEG/DOX (MP/D),
      whereas the normal brain was not affected. Magnetic Resonance Imaging (MRI)
      examinations showed that the tumour size of glioma-bearing rats in the MPI/D
      treated group was much smaller than those in the M/D and MP/D treated groups.
      Immunofluorescence results demonstrated that MPI/D treatment induced more
      apoptosis and much less proliferation than the other two treatments. However, the
      therapeutic effect was weak when IL13Ralpha2 was knocked down. Furthermore, U87
      cells treated with IL-13 and MPI together could increase both STAT6 and P63
      expression, which attenuated glioma cell proliferation, invasion and migration
      compared with cells treated with IL-13 alone. The results of the subcutaneous
      tumour model also revealed that IL13Ralpha2 knockdown could hinder cell
      proliferation and induce more apoptosis. The promising results suggested that MPI
      can not only deliver DOX to glioma in a targeted manner but also occupy
      IL13Ralpha2, which can promote IL-13 binding to IL13Ralpha1 and activation of the
      JAK-STAT pathway to induce an anti-glioma effect.

PMID- 28443898
TI  - Assessing the predictability of anharmonic vibrational modes at the example of
      hydroxyl groups - ad hoc construction of localised modes and the influence of
      structural solute-solvent motifs.
AB  - The performance of the grid-based Numerov procedure for the prediction of
      fundamental as well as the first vibrational overtone has been systematically
      probed for harmonic and anharmonic model systems. In addition to monitor the
      prediction with respect to the spacing of the potential grid the influence of
      higher order approximations to the second derivative (i.e. stencils) in
      Schrodingers equation is evaluated. The latter enable a significant increase of
      the grid-spacing to achieve results of similar accuracy obtained with smaller
      stencil sizes. Application to the hydroxyl vibrational mode of methanol, phenol
      and the natural product thymol in vacuum and carbon tetrachloride predicted
      wavenumbers within less than 1% of experiment. Due to the highly localised
      character of the OH-vibration the ad hoc construction of the associated normal
      mode yields results of similar accuracy than those obtained using the analytical
      normal modes, effectively eliminating the requirement of an analytical normal
      mode evaluation of the entire system. This property was shown to be of particular
      advantage when considering explicit solute-solvent contacts, which have been
      demonstrated to be superior compared to an implicit representation of solvent
      effects. The combination of the observed findings (i.e. enlarged grid-spacing due
      to the application of higher order stencils, construction of localised normal
      modes) is envisaged to be of particular benefit when investigating localised
      modes in large systems, such as OH or NH groups in large (bio)macromolecules or
      solid-state surfaces.

PMID- 28443899
TI  - The role of sulfur oxidation in controlling the electronic properties of sulfur
      containing host molecules for phosphorescent organic light-emitting diodes.
AB  - In this study a series of dibenzothiophene (DBT) derivatives having different
      valence states of sulfur atoms have been reported as host materials for blue
      phosphorescent organic light-emitting diodes. Their electronic properties have
      also been thoroughly investigated to develop structure-property relationships
      which include the consideration of the effect of various oxidation states of the
      sulfur atom in the core moiety and linking (C-N linkage) of subunits with the
      core at different positions. The results obtained from the electronic structure
      calculations highlight that the triplet energy (ET), singlet-triplet energy
      difference (DeltaEST), reorganization energy for the hole and the injection
      barrier for the electron decrease with an increase in the oxidation state of the
      sulfur atom in DBT. On the other hand, the injection barrier for the hole and the
      reorganization energy for the electron increase upon increasing the oxidation
      state of the sulfur atom present in the DBT.

PMID- 28443900
TI  - Toward wearable sensors: optical sensor for detection of ammonium nitrate-based
      explosives, ANFO and ANNM.
AB  - Increasing security needs require compact and portable detection tools for the
      rapid and reliable identification of explosives used in improvised explosive
      devices (IEDs). We report of an easy-to-use optical sensor for both vapour-phase
      and solution-phase identification of explosive mixtures that uses a cross
      reactive fluorimetric sensor array comprising chemically responsive fluorimetric
      indicators composed of aromatic aldehydes and polyethyleneimine. Ammonium nitrate
      nitromethane (ANNM) was analyzed by paper microzone arrays and nanofiber sensor
      mats. Progress toward wearable sensors based on electrospun nanofiber mats is
      outlined.

PMID- 28443897
TI  - Aminoquinoline-directed, cobalt-catalyzed carbonylation of sulfonamide sp2 C-H
      bonds.
AB  - We report a method for cobalt-catalyzed, aminoquinoline-directed sp2 C-H bond
      carbonylation of sulfonamides. The reactions proceed in a dichloroethane solvent,
      and employ diisopropyl azodicarboxylate as a carbon monoxide source, Mn(OAc)2 as
      a cooxidant and potassium pivalate as a base. Halogen, ester, and amide
      functionalities are compatible with the reaction conditions. This method allows
      for a short and efficient synthesis of saccharin derivatives.

PMID- 28443901
TI  - Roles of conducting filament and non-filament regions in the Ta2O5 and HfO2
      resistive switching memory for switching reliability.
AB  - The endurance of switching cycles, which is a critical measure of device
      reliability, in an ultra-thin (1.5 nm) Ta2O5 and HfO2 resistive random access
      (ReRAM) memory cell with a 28 nm lateral dimension was studied using current
      voltage (I-V) sweep and closed-loop pulse switching (CLPS) tests. The two devices
      showed the typical oxygen-deficient conducting-filament (CF)-mediated bipolar
      resistance switching behaviour, which was induced by the asymmetric electrode
      configuration: Ta as the oxygen vacancy (VO) source/reservoir and TiN as the
      inert electrode. In these device geometries, the CF is supposed to initiate at
      the oxide/TiN interface and to grow towards the Ta electrode during the switch-on
      process, while the switch-off process was induced by the contraction of the CF
      from the Ta/oxide interface. Both devices, however, showed inversion (anomalous
      SET; switching from the off- to on-state) behaviour in the RESET (switching from
      the on- to off-state) process, which can be explained by the authors' previous
      model of the hourglass-shaped CF. In this model, once the CF is ruptured, the
      RESET polarity bias makes the lower portion of the CF regrow to slightly
      reconnect such a CF through the accelerated migration of VO from the upper
      portion CF to the lower-portion CF, which induces switching performance
      degradation. In the I-V sweeps, the on- and off-states of the devices showed an
      overall conductance difference approximately corresponding to the integer
      multiple values of quantum point contact (G0), but there were arbitrary 0.25 and
      0.125G0 differences in the conductance values of the on-state for the Ta2O5 and
      HfO2 devices, respectively. This suggests that these are the minimal units of
      conductance variation even for a given CF with a standard G0. Although the
      precise reason for the emergence of such an abnormal conductance unit is not yet
      understood, its implication for the reliability is critical. Reliable resistive
      switching was achieved only for the cases where the minimum point conductance was
      retained even in the off-state; in the other cases, over-SET and over-RESET were
      induced, which eventually degraded the device reliability. The detailed
      quantitative analysis of the device failure revealed that the increasing
      concentration of VO within the non-CF region in the cell decreased the resistance
      values of that region, which eventually resulted in the over-SET and over-RESET
      behaviours during the CLPS tests.

PMID- 28443902
TI  - An internal magnetic field strategy to reuse pulverized active materials for high
      performance: a magnetic three-dimensional ordered macroporous TiO2/CoPt/alpha
      Fe2O3 nanocomposite anode.
AB  - A ferromagnetic three-dimensional ordered macroporous TiO2/CoPt/alpha-Fe2O3
      (3DOMTCF) nanocomposite was synthesized via a sol-gel approach templated by
      poly(methyl methacrylate) (PMMA) microspheres. After magnetization, it exhibited
      an extremely high reversible capacity and a long cycle life, which were ascribed
      to the internal magnetic field for reusing pulverized active materials and its
      unique structure.

PMID- 28443903
TI  - Graphene bubbles and their role in graphene quantum transport.
AB  - Graphene bubbles are often formed when graphene and other layered two-dimensional
      materials are vertically stacked as van der Waals heterostructures. Here, we
      investigate how graphene bubbles and their related disorder impact the quantum
      transport behavior of graphene in the absence and presence of external magnetic
      fields. By combining experimental observations and numerical simulations, we find
      that the disorder induced by the graphene bubbles is mainly from p-type dopants
      and the charge transport in pristine graphene can be severely influenced by the
      presence of bubbles via long- and short-range scattering even with a small bubble
      coverage of 2% and below. Upon bubble density increase, we observe an overall
      decrease in carrier mobility, and the appearance of a second Dirac point on the
      electron carrier side. At high magnetic fields, the disorder from graphene
      bubbles primarily impacts the quantization of the lowest Landau level, resulting
      in quantum Hall features associated with a new Dirac cone at high charge carrier
      density.

PMID- 28443904
TI  - Na3V2(PO4)3@nitrogen,sulfur-codoped 3D porous carbon enabling ultra-long cycle
      life sodium-ion batteries.
AB  - Na3V2(PO4)3 (NVP) is regarded as a promising cathode material for sodium ion
      batteries (NIBs) because of its 3D open structure suitable for Na
      insertion/extraction and high energy density. However, the NVP suffers from poor
      electrical conductivity, which restricts the rate performance and the long cycle
      performance of the NVP for NIBs. Here, the NVP particles embedded in the N,S co
      doped 3D porous carbon matrix (denoted as NVP@3D-NSC) were prepared by a facile
      process. The NVP@3D-NSC can deliver high specific discharge capacities at high
      rates (54 mA h g-1 at 80 C). It exhibits a super long cycle life exceeding 6000
      cycles (75 mA h g-1 at 20 C after 6000 cycles) and a low capacity-decay rate of
      0.36% per cycle. The excellent electrochemical performance of the NVP@3D-NSC is
      attributed to the specific architecture of the material that combines a variety
      of advantages: a very short diffusion length of Na+/e- in small NVP particles, a
      high contact area between the electrolyte and electrode, and a 3D porous
      structure buffering the volume change during cycling. In addition, the N,S co
      doped porous carbon matrix can not only improve the electrical conductivity, but
      also create some extrinsic defects and active sites, which can enhance the
      diffusion rate of sodium ions.

PMID- 28443905
TI  - Predicting oligomer/polymer compatibility and the impact on nanoscale segregation
      in thin films.
AB  - Compatibility between oligomers and polymers was systematically assessed using
      differential scanning calorimetry (DSC) and was correlated with similarity in
      saturation and solubility parameter. These measurements enabled validation of
      detailed volume of mixing calculations using Statistical Association Fluid Theory
      (SAFT-gamma Mie) and molecular dynamics (MD) simulations, which can be used to
      predict behaviour beyond the experimentally accessible conditions. These
      simulations confirmed that squalane is somewhat more compatible with
      poly(isoprene), "PI" than poly(butadiene), "PB", and further enabled prediction
      of the temperature dependence of compatibility. Surface and interfacial
      segregation of a series of deuterated oligomers was quantified in rubbery polymer
      films: PI, PB and hydrogenated poly(isoprene) "hPI". A striking correlation was
      established between surface wetting transition and mixtures of low compatibility,
      such as oligo-dIB in PB or PI. Segregation was quantified normal to the surface
      by ion beam analysis and neutron reflectometry and in some cases lateral
      segregation was observable by AFM. While surface segregation is driven by
      disparity in molecular weight in highly compatible systems this trend reverses as
      critical point is approached, and surface segregation increases with increasing
      oligomer molecular weight.

PMID- 28443907
TI  - Lanthanide amide-catalyzed one-pot functionalization of isatins: synthesis of
      spiro[cyclopropan-1,3'-oxindoles] and 2-oxoindolin-3-yl phosphates.
AB  - Lanthanide amide-catalyzed one-pot reaction of isatins, dialkyl phosphite, and
      activated alkenes was developed and a series of spiro[cyclopropan-1,3'-oxindoles]
      were obtained in moderate to excellent yields. The reaction is stereoselective
      and the two substituents at the 2 and 3-positions of the cyclopropane in the
      major product are in the trans configuration. A four-step mechanism involving the
      Pudovik reaction, Brook rearrangement, Michael addition, and intramolecular
      nucleophilic substitution is proposed, and an umpolung strategy was used in the
      process.

PMID- 28443906
TI  - The enhanced anti-obesity effect and reduced gastric mucosa irritation of
      capsaicin-loaded nanoemulsions.
AB  - Capsaicin (CAP), the major active component of chili peppers, is known to have
      thermogenic and weight-loss potential. The aim of this study was to investigate
      the anti-obesity effects of capsaicin-loaded nanoemulsions (C-NE) on male Sprague
      Dawley (SD) rats treated with a high-fat diet (HFD). The food grade C-NE was
      prepared using capsaicin, medium chain triacylglycerols (MCT) (Neobee 1053),
      sucrose stearate S-370, Tween 80 and distilled water with an emulsion droplet
      size of 168 nm and a capsaicin loading of 80.4 mg mL-1. Results showed that C-NE
      effectively decreased body weight gain and hypercholesterolemia induced by HFD in
      a dose-dependent manner. Histological evaluations of the liver and adipose tissue
      confirmed that C-NE had significant effects on inhibiting diet-induced hepatic
      steatosis, reducing epididymal adipocyte size and tissue mass. A gastric mucosa
      irritation test demonstrated that C-NE was effective in alleviating the gastric
      inflammation caused by free unformulated CAP crystals.

PMID- 28443908
TI  - Polyvalent C-glycomimetics based on l-fucose or d-mannose as potent DC-SIGN
      antagonists.
AB  - The C-type lectin DC-SIGN expressed on immature dendritic cells is a promising
      target for antiviral drug development. Previously, we have demonstrated that mono
      and divalent C-glycosides based on d-manno and l-fuco configurations are
      promising DC-SIGN ligands. Here, we described the convergent synthesis of C
      glycoside dendrimers decorated with 4, 6, 9, and 12 alpha-l-fucopyranosyl units
      and with 9 and 12 alpha-d-mannopyranosyl units. Their affinity against DC-SIGN
      was assessed by surface plasmon resonance (SPR) assays. For comparison, parent O
      glycosidic dendrimers were synthesized and tested, as well. A clear increase of
      both affinity and multivalency effect was observed for C-glycomimetics of both
      types (mannose and fucose). However, when dodecavalent C-glycosidic dendrimers
      were compared, there was no difference in affinity regarding the sugar unit (l
      fuco, IC50 17 MUM; d-manno, IC50 12 MUM). For the rest of glycodendrimers with l
      fucose or d-mannose attached by the O- or C-glycosidic linkage, C-glycosidic
      dendrimers were significantly more active. These results show that in addition to
      the expected physiological stability, the biological activity of C-glycoside
      mimetics is higher in comparison to the corresponding O-glycosides and therefore
      these glycomimetic multivalent systems represent potentially promising candidates
      for targeting DC-SIGN.

PMID- 28443909
TI  - Effect of the calcination temperature on the photocatalytic efficiency of acidic
      sol-gel synthesized TiO2 nanoparticles in the degradation of alprazolam.
AB  - We report a comparative study on the photodegradation of the widely used
      benzodiazepine psychoactive drug alprazolam (8-chloro-1-methyl-6-phenyl-4H
      [1,2,4]triazolo[4,3-a][1,4]benzodiazepine, ALP) using direct photolysis, and
      titanium dioxide photocatalyzed reaction. Titanium dioxide photocatalysts were
      prepared as nanoparticles by acidic sol-gel methods, calcined at two different
      temperatures, and their behavior compared with P25 (Degussa type) TiO2. Efficient
      photodegradation was observed in the photocatalytic process, with over 90%
      degradation after 90 minutes under optimized conditions. Triazolaminoquinoline, 5
      chloro-(5-methyl-4H-1,2,4-triazol-4-yl)benzophenone, triazolbenzophenone, and
      alpha-hydroxyalprazolam were identified as the degradation products by
      fluorescence spectroscopy and HPLC-MS. A comparison with the literature suggests
      that 8H-alprazolam may also be formed. Good mineralization was observed with TiO2
      photocatalysts. ALP photodegradation with TiO2 follows pseudo-first order
      kinetics, with rates depending on the photocatalyst used. The effects of the
      quantity of the photocatalyst and concentration of alprazolam were studied.

PMID- 28443910
TI  - Spin state variability in Fe2+ complexes of substituted (2-(pyridin-2-yl)-1,10
      phenanthroline) ligands as versatile terpyridine analogues.
AB  - Fe2+ spin crossover complexes [Fe(L)2]2+ (L = 2-(6-R1-pyridin-2-yl)-1,10
      phenanthroline with R1 = H, methoxy, bromo, -(1H-pyrazol-1-yl) or L = 2-(3
      methoxy-pyridin-2-yl)-1,10-phenanthroline) were prepared. These air stable and
      durable complexes show SCO behaviour with very different transition temperatures
      T1/2 ranging from 130 K to 600 K depending on the substitution pattern. The use
      of 1H NMR spectroscopy to elucidate the thermodynamics and kinetics of SCO in a
      solution of this series is described in detail. By introduction of an additional
      pyrazole donor (R1) in the ortho-position to the pyridine, the N6 octahedral
      coordination sphere is expanded to N8 coordination with a trigonal dodecahedral
      structure. This leads to a strong stabilization of the high spin state and an
      increased longitudinal relaxation R1 of the proton spins. The larger R1 values
      were ascribed to different electronic structures with non-orbital degenerate
      quintet ground states and a larger energetic separation from the first excited
      state. These results are also supported by Mossbauer spectroscopy. The N8
      coordination sphere stabilizes the complex in the high spin state and no
      indication for SCO was found. DFT calculations confirmed the experimentally
      obtained order of T1/2 and allowed the calculation of the complex structure in
      experimentally non-accessible spin states. Complexes of this series can be
      oxidized to the Fe3+ complexes in a chemically reversible fashion. Interestingly,
      the lowest oxidation potential was observed for the N8 coordinated complex.

PMID- 28443911
TI  - Fabrication of plasmonic Au-Pd alloy nanoparticles for photocatalytic Suzuki
      Miyaura reactions under ambient conditions.
AB  - The Suzuki-Miyaura reaction is one of the most popular and efficient routes for
      the formation of carbon-carbon bonds in both laboratorial and industrial
      synthetic processes. Here, we report for the first time that a Au-Pd/TiO2
      catalyst could be utilized efficiently for Suzuki-Miyaura reactions at ambient
      conditions under visible light with high activity and reusability. Mechanistic
      investigation by means of experimental methods revealed that through the strong
      local surface plasma resonance of Au under the visible light, the hot electrons
      of Au could be injected into Pd in the bimetallic nanoparticles, thus
      facilitating activation of the aryl halides. Meanwhile, the electropositive Au
      tended to gain electrons from TiO2, resulting in the separation of the
      photogenerated electron/hole pairs of TiO2, which enabled the holes to activate
      aryl boronic acids. This Au-Pd/TiO2 catalyst not only expands the application
      scope of Suzuki-Miyaura reactions under mild conditions but will also inspire
      further exploitation of the direct harvesting of visible light by nanomaterials
      for a wide range of chemical reactions.

PMID- 28443912
TI  - Flux synthesis, crystal structures, and physical properties of new lanthanum
      vanadium oxyselenides.
AB  - The new lanthanum vanadium oxyselenides LaVSe2O, La5V3Se6O7, La5V3Se7O5,
      La7VSe5O7, and La13V7Se16O15 were synthesized in eutectic NaI/KI fluxes, and
      their crystal structures were determined using single-crystal and powder X-ray
      diffraction experiments. LaVSe2O and La5V3Se6O7 adopt known structure types,
      whereas La5V3Se7O5, La7VSe5O7, and La13V7Se16O15 crystallize in hitherto unknown
      structure types. The main building blocks of these compounds are chains of edge
      sharing VSe6, VSe5O, and/or VSe4O2 octahedra, linked together by edge-sharing
      OLa4 and/or OLa3V tetrahedra forming fluorite-like ribbons. LaVSe2O, La5V3Se7O5,
      and La7VSe5O7 contain only V(iii) ions, whereby La5V3Se6O7 and La13V7Se16O15
      contain mixtures of either V(iii)/V(iv) or V(iii)/V(v) cations. Magnetic
      measurements indicate Curie-Weiss paramagnetism and magnetic ordering of the
      vanadium moments at low temperatures. More precisely, we observe
      antiferromagnetism for La5V3Se6O7, metamagnetism for La5V3Se7O5, ferromagnetism
      for La7VSe5O7 and a complex magnetic structure for La13V7Se16O15.

PMID- 28443913
TI  - The effect of surface roughness and viscoelasticity on rubber adhesion.
AB  - Adhesion between silica glass or acrylic balls and silicone elastomers and
      various industrial rubbers is investigated. The work of adhesion during pull-off
      is found to strongly vary depending on the system, which we attribute to the two
      opposite effects: (1) viscoelastic energy dissipation close to an opening crack
      tip and (2) surface roughness. Introducing surface roughness on the glass ball is
      found to increase the work of adhesion for soft elastomers, while for the stiffer
      elastomers it results in a strong reduction in the work of adhesion. For the soft
      silicone elastomers a strong increase in the work of adhesion with increasing
      pull-off velocity is observed, which may result from the non-adiabatic processes
      associated with molecular chain pull-out. In general, the work of adhesion is
      decreased after repeated contacts due to the transfer of molecules from the
      elastomers to the glass ball. Thus, extracting the free chains (oligomers) from
      the silicone elastomers is shown to make the work of adhesion independent of the
      number of contacts. The viscoelastic properties (linear and nonlinear) of all of
      the rubber compounds are measured, and the velocity dependent crack opening
      propagation energy at the interface is calculated. Silicone elastomers show a
      good agreement between the measured work of adhesion and the predicted results,
      but carbon black filled hydrogenated nitrile butadiene rubber compounds reveal
      that strain softening at the crack tip may play an important role in determining
      the work of adhesion. Additionally, adhesion measurement under submerged
      conditions in distilled water and water + soap solutions are also performed: a
      strong reduction in the work of adhesion is measured for the silicone elastomers
      submerged in water, and a complete elimination of adhesion is found for the water
      + soap solution attributed to an osmotic repulsion between the negatively charged
      surface of the glass and the elastomer.

PMID- 28443914
TI  - Probing the pharmacokinetics of cucurbit[7, 8 and 10]uril: and a dinuclear
      ruthenium antimicrobial complex encapsulated in cucurbit[10]uril.
AB  - The relatively non-toxic family of cucurbit[n]uril, Q[n], have shown considerable
      potential in vitro as drug delivery agents, with only a few examples of
      pharmacokinetic (PK) studies for drug?Q[n]. Drug-free Q[n] PK studies are the
      next step in determining the pharmacological applicability in their drug delivery
      potential. The results for the first PK and bio-distribution of drug-free 14C
      Q[7] are described for administration via intravenous (i.v.) and intraperitoneal
      (i.p.) dosing. A study of oral administration of drug-free 14C-Q[8] has also been
      undertaken to determine the time course for the gastrointestinal tract (GIT),
      absorption and subsequent bio-distribution. Q[10], a potential drug carrier for
      larger drugs, was evaluated for its effect on the PK profile of a dinuclear
      ruthenium complex (Rubb12), a potential antimicrobial agent. The Rubb12?Q[10]
      complex and free Rubb12 were administered by i.v. to determine differences in
      Rubb12 plasma concentrations and organ accumulation. Interestingly, the PK
      profiles and bio-distribution observed for Q[7] showed similarities to those of
      Rubb12?Q[10]. Drug-free Q[7] has a relatively fast plasma clearance and a
      generally low organ accumulation except for the kidneys. Drug-free Q[8] showed a
      low absorption from the GIT into the blood stream but the small percentage
      absorbed reflected the organ accumulation of Q[7]. These results provide a better
      understanding of the probable PK profile and bio-distribution for a drug?Q[n]
      through the influence of the drug delivery vehicle and the positive clearance of
      drug-free Q[n] via the kidneys supports its potential value in future drug
      delivery applications.

PMID- 28443915
TI  - Photochemical studies on bis-sulfide and -sulfone tethered polyenic derivatives.
AB  - This study focusses on the [2 + 2]-photocycloaddition of a symmetric polyenic
      system tethered by an aryl bis-sulfide or sulfone platform. Using direct
      irradiation or photosensitization, no expected ladderane product was isolated. In
      most cases, only tricyclic products including a single cyclobutane moiety were
      formed. Irradiation of bis-acrylic precursors in water with encapsulation by a
      host (cyclodextrin or cucurbituril) provided a stereoselective access to valuable
      cyclobutyl adducts.

PMID- 28443916
TI  - A kinetic model of water adsorption, clustering and dissociation on the
      Fe3S4{001} surface.
AB  - The interaction of water with catalyst surfaces is a common process which
      requires investigation. Here, we have employed density functional theory
      calculations to investigate the adsorption of up to ten water molecules on the
      {001} surface of greigite (Fe3S4), which owing to its redox properties, is of
      increasing interest as a catalyst, e.g. in electro-catalysis. We have
      systematically analyzed and characterized the modes of water adsorption on the
      surface, where we have considered both molecular and dissociative adsorption
      processes. The calculations show that molecular adsorption is the predominant
      state on these surfaces, from both a thermodynamic and kinetic point of view. We
      have explored the molecular dispersion on the surface under different coverages
      and found that the orientation of the molecule, and therefore the surface dipole,
      depends on the number of adsorbed molecules. The interactions between the water
      molecules become stronger with an increasing number of water molecules, following
      an exponential decay which tends to the interaction energy found in bulk water.
      We have also shown the evolution of the infra-red signals as a function of water
      coverage relating to the H-bond networks formed on the surface. Next we have
      included these results in a classical micro-kinetic model, which introduced the
      effects of temperature in the simulations, thus helping us to derive the water
      cluster size on the greigite surface as a function of the initial conditions of
      pressure, temperature and external potential. The kinetic model concluded that
      water molecules agglomerate in clusters instead of wetting the surface, which
      agrees with the low hydrophilicity of Fe3S4. Clusters consisting of four water
      molecules was shown to be the most stable cluster under a wide range of
      temperatures and external potential.

PMID- 28443917
TI  - Hydrogen purification performance of a nanoporous hexagonal boron nitride
      membrane: molecular dynamics and first-principle simulations.
AB  - Membranes have attracted much attention for the efficient separation of gas
      mixtures, due to their specific structural and unique properties. In this work,
      density functional theory (DFT) and molecular dynamic (MD) simulations have been
      employed to evaluate the performance of nanoporous hexagonal boron nitride (h-BN)
      monolayers for hydrogen purification. Various porous membranes were designed, and
      full structural relaxation was carried out by using DFT calculations and then MD
      simulations to investigate the H2 purification performance of the nanoporous h-BN
      membranes. It was found that the selectivity for H2 gas over N2 gas was highly
      sensitive to the type and width of the pores. The h-BN membrane containing pores
      with short and long sides both of about 3 A (pore 1B-3N) demonstrated optimal
      selectivity for H2 molecules, while the permeability of the pore 5B-5N + 4H
      membrane (short side of about 4.4 A) was much higher than that of other
      counterparts. Furthermore, DFT calculations were performed to validate the MD
      simulation observations as well as to explain the selectivity performance of the
      most desirable pore membrane. We demonstrated that the 1B-3N pore is a far
      superior membrane to other counterparts and exhibits an excellent potential for
      applications in hydrogen purification, clean energy combustion, and the design of
      novel membranes for gas separation.

PMID- 28443918
TI  - pH Responsiveness of hydrogels formed by telechelic polyampholytes.
AB  - We investigate the influence of pH on the rheological and structural properties
      of hydrogels formed by hydrophobic association of the sticky ends of the triblock
      terpolymer poly(methyl methacrylate)-b-poly(2-(diethylamino)ethyl methacrylate-co
      methacrylic acid)-b-poly(methyl methacrylate) (PMMA-b-P(DEA-co-MAA)-b-PMMA). The
      middle block is a weak polyampholyte having a pH dependent charge density and
      sign, which enables tuning of the rheological and structural properties by pH
      variation. Small-angle neutron scattering (SANS) studies of solutions in D2O at
      0.05 wt% and pH 3.0 reveal clusters of interconnected spherical micelles having
      PMMA cores, stabilized by repulsive ionic interactions in the middle
      polyampholyte block. With increasing pH, the degree of ionization of the DEA
      units decreases, whereas the one of the MAA units increases, resulting in a
      complete loss of the correlation between these micelles. At a concentration of 3
      wt% at low pH values, the system forms a gel with charged fuzzy spheres from PMMA
      interacting via a screened Coulomb potential. With increasing pH, the gel
      disintegrates due to the decrease in the effective charge on the micelles. At
      both concentrations, the hydrophobic aggregation of micelles is observed near the
      isoelectric point. At pH 3.0-7.4, the autocorrelation functions measured by
      rotational dynamic light scattering at 3 wt% exhibit a decay steeper than single
      exponential, which confirms that the gels are frozen, presumably due to the
      glassy PMMA cores and hydrophobic interpolyelectrolyte complexes. At pH 11, the
      diffusion of single micelles is observed in addition to the frozen dynamics.

PMID- 28443919
TI  - The dearomative annulation between N-2-pyridylamidine and CO2 toward pyrido[1,2
      a]-1,3,5-triazin-4-ones.
AB  - A base-promoted dearomative annulation between N-2-pyridylamidine and an
      atmospheric pressure of CO2 was developed, affording a series of pyrido[1,2-a]
      1,3,5-triazin-4-ones in moderate to excellent yields. CO2 served as a carbonyl
      source, releasing H2O as a solely clean byproduct. Moreover, no dehydrating
      reagent and transition-metal catalyst were required in this procedure. Thus, it
      represents a green, sustainable and straightforward pathway to access such
      frameworks.

PMID- 28443920
TI  - How does substitution affect the unimolecular reaction rates of Criegee
      intermediates?
AB  - To gain an understanding of the substitution effect on the unimolecular reaction
      rate coefficients for Criegee intermediates (CIs), we performed ab initio
      calculations for CH2OO, CH3CHOO, (CH3)2COO, CH3CH2CHOO, CH2CHCHOO and CHCCHOO.
      The energies of the CIs, products and transition states were calculated with
      QCISD(T)/CBS//B3LYP/6-311+G(2d,2p), while the rate coefficients were calculated
      with anharmonic vibrational correction by using second order vibrational
      perturbation theory. It was found that for single bonded substitutions, the
      hydrogen transfer reaction dominates for the syn-conformers, while the OO bending
      reaction dominates for the anti-conformers. However once a double bond or a
      triple bond is added, the OO bending reaction dominates for both syn and anti
      conformers. The rate coefficients for OO bending reaction show a significant
      increase when adding a methyl group or ethyl group. On the other hand, the
      addition of unsaturated vinyl and acetylene groups usually results in a slower
      thermal decomposition compared to the substitution with saturated carbon groups.
      Interestingly, for syn_Syn-CH2CHCHOO, a special five member ring closure reaction
      forming dioxole was calculated to have an extremely fast rate coefficient of 9312
      s-1 at room temperature.

PMID- 28443921
TI  - Asymmetric conjugate additions of 2-substituted benzofuran-3(2H)-ones to
      alpha,beta-unsaturated ketones catalyzed by chiral copper complexes.
AB  - A highly enantioselective conjugate addition of 2-substituted benzofuran-3(2H)
      ones to alpha,beta-unsaturated ketones promoted by chiral copper complexes has
      been developed, affording the Michael addition products with quaternary
      stereocenters in good to high yields (up to 95% yield) with excellent
      enantioselectivities (up to 99% ee). The chiral Michael adducts could be readily
      converted to the polycyclic benzofuran-type framework via the Robinson
      annulation.

PMID- 28443922
TI  - Friction, lubrication, and in situ mechanics of poroelastic cellulose hydrogels.
AB  - The tribology between biphasic materials is challenging to predict and interpret
      due to the interrelationship between mechanical properties, microstructure and
      movement of the fluid phase contained within. A new approach is presented to
      deconvolute these effects for cellulose hydrogels, which have a fibrous network
      that is akin to the microstructure of articular cartilage and plant cell walls.
      This is achieved by developing a tribo-rheological technique that uniquely
      incorporates in situ mechanical characterisation (compression-relaxation and
      small amplitude oscillatory shear) immediately prior to measuring the
      tribological response between pairs of hydrogels. A radial pressure gradient is
      generated upon compression-relaxation of the poroelastic hydrogels that results
      in a non-uniform film thickness at the interface between them. Simulations of
      this process show that contact between gels occurs in an outer annulus region.
      Accounting for the predicted contact area between hydrogels varying in cellulose
      density and pectin solution viscosity causes measured tribology data to collapse
      onto a single curve; the apparent static friction between hydrogel tribopairs
      increases with the storage modulus of the hydrogels according to a power law with
      exponent 0.67. The method is used to compare the influence of plant cell wall
      polysaccharides, xyloglucan and arabinoxylan, on the interactive forces between
      cellulose fibres; xyloglucan is found to reduce the static friction between the
      hydrogels while arabinoxylan had no significant effect. The methodologies
      presented should provide a new framework for studying the friction between gels
      and other biphasic soft materials and polymeric surface films.

PMID- 28443923
TI  - Use of AlCl3 in Friedel Crafts arylation type reactions and beyond: an overview
      on the development of unique methodologies leading to N-heteroarenes.
AB  - As a privileged class of heterocyclic compounds N-heteroarenes have found
      enormous applications in many areas including medicinal/pharmaceutical chemistry
      and drug discovery. Consequently, a wide variety of methods have been reported
      for their synthesis. While not free from their own limitations the AlCl3 mediated
      methods appeared to have some particular advantages in preparing a number of
      useful N-heteroarenes. Besides the famous Friedel-Crafts (FC)
      alkylation/acylation reactions one such example is AlCl3-induced heteroarylation
      of arenes and heteroarenes (FC arylation type reactions) that can be used to
      prepare a certain class of N-heteroarenes in an operationally simple, efficient
      and cost effective manner. Interestingly, pyridine is not a good substrate in FC
      alkylation/acylation reactions whereas 2-chloropyridines are indeed effective in
      heteroarylation reaction. However, no systematic and detailed study regarding the
      application potential of this method was performed until 2002. Some other
      examples that emerged in the recent past include AlCl3 induced heteroarylation
      cyclization, hydroarylation-heteroarylation, sulfonyl group migration etc. All
      these innovative methodologies allowed the direct access to several unique and
      novel N-heteroarenes some of which showed interesting pharmacological properties
      including anti-inflammatory, anti-cancer and antibacterial activities when tested
      in vitro. While unlike FC reactions many of these AlCl3 mediated methodologies
      are still in their initial stage of developments, a continuing effort to uncover
      their further potential in organic synthesis/medicinal chemistry is necessary.
      The current article provides an overview of these unique methodologies that
      highlight the use of AlCl3 beyond FC reactions leading to new N-heteroarenes.

PMID- 28443924
TI  - Investigations on the photochromic properties of 2,6-bis(5-bromo-2
      hydroxybenzylidene)cyclohexanone.
AB  - The network of chemical reactions of 2,6-bis(5-bromo-2
      hydroxybenzylidene)cyclohexanone (BHBC) when subjected to light and different pH
      values has been investigated. The pH dependent species involved in the chemical
      network have been identified and characterized by NMR and UV-VIS spectroscopy.
      Direct pH jumps were carried out by adding a strong acid to equilibrated
      solutions of trans-chalcone (Ct) forming the flavylium cation which was stable
      only under extremely acidic conditions (pH < 0.5). The single crystal X-ray study
      and NMR analysis has confirmed the structure of the new flavylium cation. In the
      case of a reverse pH jump, the Ct species interconverted instantaneously into
      deprotonated trans-chalcone (Ct2-) around pH 12. A new colorless compound 3,11
      dibromo-7,8-dihydro-6H-chromeno[3,2-d]xanthene (B-B) isolated from the
      equilibrated solution of trans-chalcone species in methanol after long periods of
      time (100 h) under dark conditions has been isolated and fully characterized by
      NMR and X-ray diffraction. The rate of the reaction increased when the solution
      of trans-chalcone was exposed to light and the total conversion of Ct into the
      spiropyran-like compound (B-B) was achieved in about 30 minutes. The B-B form was
      stable under neutral and basic conditions, while at low pH values it converts
      into a cationic AH+ form.

PMID- 28443926
TI  - Defect induced ferromagnetism in MgO and its exceptional enhancement upon thermal
      annealing: a case of transformation of various defect states.
AB  - MgO particles of few micron size are synthesized through a sol-gel method at
      different annealing temperatures such as 600  degrees C (MgO-600), 800  degrees C
      (MgO-800) and 1000  degrees C (MgO-1000). EDX and ICP-AES studies confirmed a
      near total purity of the sample with respect to paramagnetic metal ion
      impurities. Magnetic measurements showed a low temperature weak ferromagnetic
      ordering with a TC (Curie temperature) around 65 K (+/-5 K). Unexpectedly, the
      saturation magnetization (Ms) was found to be increased with increasing annealing
      temperature during synthesis. It was observed that with J = 1 or 3/2 or S = 1 or
      3/2, the experimental points are fitted well with the Brillouin function of weak
      ferromagnetic ordering. A positron annihilation lifetime measurement study
      indicated the presence of a divacancy (2VMg + 2VO) cluster in the case of the low
      temperature annealed compound, which underwent dissociations into isolated
      monovacancies of Mg and O at higher annealing temperatures. An EPR study showed
      that both singly charged Mg vacancies and oxygen vacancies are responsible for
      ferromagnetic ordering. It also showed that at lower annealing temperatures the
      contribution from was very low while at higher annealing temperatures, it
      increased significantly. A PL study showed that most of the F+ centers were
      present in their dimer form, i.e. as centers. DFT calculation implied that this
      dimer form has a higher magnetic moment than the monomer. After a careful
      consideration of all these observations, which have been reported for the first
      time, this thermally tunable unusual magnetism phenomenon was attributed to a
      transformation mechanism of one kind of cluster vacancy to another.

PMID- 28443925
TI  - The effect of ligand-ligand interactions on the formation of photoluminescent
      gold nanoclusters embedded in Au(i)-thiolate supramolecules.
AB  - In this study, we prepared photoluminescent l-cysteine (Cys)-capped gold
      nanoclusters (Cys-Au NCs) via NaBH4-mediated reduction of aggregated coordination
      polymers (supramolecules) of -[Cys-Au(i)]n-. The -[Cys-Au(i)]n- supramolecules
      with interesting chiral properties were formed through simple reactions of
      chloroauric acid (HAuCl4) with Cys at certain pH values (pH 3-7). The -[Cys
      Au(i)]n- polymers could self-assemble into -[Cys-Au(i)]n- supramolecules with
      irregular morphologies and diameters larger than 500 nm through stacked hydrogen
      bonding and zwitterionic interactions between Cys ligands and through Au(i)Au(i)
      aurophilic interactions in solutions with pH values <=7. The photoluminescent Au
      NCs (quantum yield = 11.6%) dominated by a Au13 core were embedded in -[Cys
      Au(i)]n- supramolecules after NaBH4-mediated reduction. The optical and
      structural properties of Cys-Au NCs/-[Cys-Au(i)]n- nanocomposites were
      investigated, revealing that the interaction between Cys ligands plays a critical
      role in the self-assembly of -[Cys-Au(i)]n- supramolecules and in the formation
      of photoluminescent Cys-Au NCs embedded in the supramolecules. To further
      demonstrate that the photoluminescence properties and structures of the
      nanocomposites are mediated by the intermolecular forces of thiol ligands, other
      thiol ligands (l-penicillamine, l-homocysteine, 3-mercaptopropionic acid, and l
      glutathione) and a ligand-crosslinking agent [bis(sulfosuccinimidyl) suberate;
      BS3] were used. We concluded that the electrostatic interactions, hydrogen
      bonding and steric effects dominate the polymer self-assembly into thiol-ligand
      Au(i) supramolecules and thus the formation of Au NCs. Our study provides
      insights into the bottom-up synthesis of photoluminescent Au NCs from thiol
      ligand-Au(i) complexes, polymers, and supramolecules. The hybrid Au NCs/-[Cys
      Au(i)]n- nanocomposites can potentially be employed as drug carriers and
      bioimaging agents.

PMID- 28443927
TI  - Direct oxidation of the C(sp2)-C(sp3) bond from benzyltrimethylsilanes to
      phenols.
AB  - A novel pathway for direct conversion of benzylsilanes to phenols by oxidation
      with Na2S2O8 and oxygen is efficiently developed under mild and neutral
      conditions. The reaction shows good functional group tolerance to afford phenols
      in moderate yields. The possible mechanism is proposed based on the isotopic
      labeling trials.

PMID- 28443928
TI  - A new four-component reaction involving the Michael addition and the Gewald
      reaction, leading to diverse biologically active 2-aminothiophenes.
AB  - The Gewald three-component reaction yielding highly substituted 2-aminothiophene
      heterocycles has been known for a long time and holds an extraordinary potential
      in the pharmaceutical industry. Herein, we describe a four-component reaction
      initiated by the conjugate addition of different indole derivatives to alpha,beta
      unsaturated carbonyl compounds. This is followed by an in situ Gewald three
      component reaction which results in the formation of a compound containing an
      indole and a 2-aminothiophene moiety separated by a methylene spacer. We also
      examined the impact of the use of other nucleophilic components such as pyrrole
      derivatives on this MG-4CR (Michael-Gewald four component reaction). All these
      synthesized compounds were tested for anti-proliferative activity and three of
      them showed activity in the nanomolar range.

PMID- 28443929
TI  - Construction of protein assemblies by host-guest interactions with cucurbiturils.
AB  - Protein assemblies are extremely interesting in chemistry and supramolecular
      chemistry. How to design protein assemblies with dimensional structures is
      important for applications. To address this challenge, cucurbituril (CB[n]s)
      based strategies have been explored owing to their high affinity toward small
      peptide motifs, organic cations and amines. By incorporation of a small molecule
      guest and a peptide motif guest into N-terminals of oligomeric proteins, CB[n]s
      could recognize and bind to the N-terminal guests, leading to dimensional protein
      assemblies. The dimensional protein assemblies possess structural, stimuli
      responsive and bioactive properties with great potential for in vivo
      applications. Herein, we reviewed the progress in the design of dimensional
      protein assemblies based on supramolecular interactions of CB[n]s and present the
      perspectives in the design of high-ordered biomaterials for biomedical
      applications.

PMID- 28443930
TI  - A multiconfigurational approach to the electronic structure of trichromium
      extended metal atom chains.
AB  - Density functional theory, Complete Active Space Self-Consistent Field (CASSCF)
      and perturbation theory (CASPT2) methodologies have been used to explore the
      electronic structure of a series of trichromium Extended Metal Atom Chains
      (EMACS) with different capping ligands. The study is motivated by the very
      different structural properties of these systems observed in X-ray experiments:
      the CN--capped example has a symmetric Cr3 unit while for the NO3--capped
      analogue the same unit has two very different Cr-Cr bond lengths. Density
      functional theory fails to locate an unsymmetric minimum for any of the systems
      studied, although the surface corresponding to the asymmetric stretch is very
      flat. CASPT2, in contrast, does locate an unsymmetric minimum only for the NO3-
      capped system, although again the surface is very flat. We use the Generalized
      active space (GASSCF) technique and effective Hamiltonian theory to interrogate
      the multi-configurational wavefunctions of these systems, and show that the
      increase in the sigma-sigma* separation as the chain becomes unsymmetric plays a
      defining role in the stability of the ground state and its expansion in terms of
      configuration state functions.

PMID- 28443931
TI  - The effect of temperature, composition and alcohols on the microstructures of
      catanionic mixtures of sodium dodecylsulfate and cetyltrimethylammonium bromide
      in water.
AB  - The influence of mixing protocol, composition, temperature, ageing and added
      alcohols on the characteristics of the microstructures of sodium dodecylsulfate
      (SDS) + cetyltrimethylammonium bromide (CTAB) mixtures has been investigated in
      this paper. In this catanionic mixture (1 weight% total surfactant content)
      temperature induced microstructural transition occurs, which is (i) a micelle-to
      vesicle transition (MVT) if alphaSDS (mole fraction of SDS) = 0.7, 0.8 or 0.9 and
      (ii) a vesicle-to-micelle transition (VMT) if alphaSDS = 0.1, 0.2 or 0.3. In the
      mixture of alphaSDS = 0.7, specific conductivity and dynamic light scattering
      measurements also support the occurrence of MVT. Transition electron microscopy
      and small angle neutron scattering measurements were also made to assess the
      characteristics of the microstructures. Alcohols added to the mixture of alphaSDS
      = 0.7 reduced the size of the vesicle, while only monohydric alcohols suppressed
      the temperature induced transition indicating that the number and location of -OH
      groups of the alcohols have a dramatic modulating influence on the structural
      transition occurring in catanionic mixtures. The influence of the alcohols is
      explained in terms of changes produced in the dielectric constant and
      hydrophobicity of the medium.

PMID- 28443933
TI  - High-performance Schottky heterojunction photodetector with directly grown
      graphene nanowalls as electrodes.
AB  - Schottky heterojunctions based on graphene-silicon structures are promising for
      high-performance photodetectors. However, existing fabrication processes adopt
      transferred graphene as electrodes, limiting process compatibility and generating
      pollution because of the metal catalyst. In this report, photodetectors are
      fabricated using directly grown graphene nanowalls (GNWs) as electrodes. Due to
      the metal-free growth process, GNWs-Si heterojunctions with an ultralow measured
      current noise of 3.1 fA Hz-1/2 are obtained, and the as-prepared photodetectors
      demonstrate specific detectivities of 5.88 * 1013 cm Hz1/2 W-1 and 2.27 * 1014 cm
      Hz1/2 W-1 based on the measured and calculated noise current, respectively, under
      ambient conditions. These are among the highest reported values for planar
      silicon Schottky photodetectors. In addition, an on/off ratio of 2 * 107, time
      response of 40 MUs, cut-off frequency of 8.5 kHz and responsivity of 0.52 A W-1
      are simultaneously realized. The ultralow current noise is attributed to the
      excellent junction quality with a barrier height of 0.69 eV and an ideal factor
      of 1.18. Furthermore, obvious infrared photoresponse is observed in blackbody
      tests, and potential applications based on the photo-thermionic effect are
      discussed.

PMID- 28443932
TI  - Nucleoside-linked shunt products in the reaction catalyzed by the class C radical
      S-adenosylmethionine methyltransferase NosN.
AB  - NosN is a class C radical S-adenosylmethionine (SAM) methyltransferase (RSMT)
      involved in the biosynthesis of nosiheptide, a clinically interesting thiopeptide
      antibiotic produced by Streptomyces actuosus. NosN employs an unprecedented
      catalytic mechanism, in which SAM is converted to 5'-methylthioadenosine (MTA) as
      a direct methyl donor. In this study, we report identification of several
      nucleoside-linked shunt products in the NosN-catalyzed reaction. Comparative
      analysis of NosN and the class A RSMT RlmN and further density functional theory
      (DFT) calculations reveal important mechanistic insights into the catalyses of
      the two types of enzymes, showing that the radical intermediates generated by
      similar pathways can have very diverse reactivities. This investigation provides
      strong evidence supporting the previous mechanistic proposal of NosN catalysis,
      validating the presence of a key radical adduct that results from the addition of
      an MTA-derived methylene radical onto the C4 of the indolyl substrate.

PMID- 28443934
TI  - Hg(ii) and Pd(ii) complexes with a new selenoether bridged biscarbene ligand:
      efficient mono- and bis-arylation of methyl acrylate with a pincer biscarbene
      Pd(ii) precatalyst.
AB  - Two equivalents of 1-benzyl-3-bromoethylbenzimidazolium bromide couple with Na2Se
      to produce the first selenoether bridged bis-benzimidazolium salt (LH2)Br2. The
      nitrate (LH2)(NO3)2 and tetrafluoroborate (LH2)(BF4)2 salts were also synthesized
      from (LH2)Br2. The reaction of Hg(OAc)2 with (LH2)Br2 gave the first pseudo
      pincer carbene mercury complex, [Hg(L-kappa2C)][HgBr4] (C1). Different complexes
      of Pd(ii) with selenoether bridged carbene were obtained using (LH2)Br2 and
      (LH2)(NO3)2. Syntheses of these complexes were dependent on the counter anion and
      the temperature. Thus, the pincer type ionic complex [PdBr(L-kappa3CSeC)]Br (C2)
      was isolated at 80  degrees C and the pseudo pincer type neutral complex cis
      [PdBr2(L-kappa2C)] (C3) was isolated at room temperature from (LH2)Br2 and
      Pd(OAc)2 in DMSO. The nitrate precursor (LH2)(NO3)2 on palladation with Pd(OAc)2
      afforded [Pd(L-kappa4CBzCSeC)]NO3 (C4) showing an unprecedented intramolecular
      metallation at the ortho position of the benzyl wingtip of the benzimidazole
      moiety. The ligand salts and metal complexes have been characterized using HRMS,
      heteronuclear NMR and IR spectroscopy. Single crystal X-ray structures of the
      ligand salts (LH2)Br2 and (LH2)(BF4)2 and complexes C1-C4 have also been
      elucidated. Complex C2 showed good activity for C-C coupling in the mono-Heck
      reaction of methyl acrylate and arylbromides. Interestingly, the less common bis
      arylation was also observed with deactivated arylbromides as the result of double
      Heck coupling.

PMID- 28443935
TI  - Regiocontrolled functionalization of 2,3-dihalogenoimidazo[1,2-a]pyridines by
      Suzuki-Miyaura and Sonogashira cross-coupling reactions.
AB  - An efficient method for regiocontrolled functionalization of 2,3
      dihalogenoimidazo[1,2-a]pyridine was developed. This sequence allowed the
      selective introduction of aryl, heteroaryl, alkyl and alkynyl substituents at
      both 2- and 3-positions, by using Suzuki-Miyaura and Sonogashira cross-coupling
      reactions. A library of compounds diversely substituted on 2- and 3-positions can
      be easily prepared from a common, stable and easily accessible starting material.

PMID- 28443936
TI  - Effects of graphene defects on gas sensing properties towards NO2 detection.
AB  - The crystal structure of graphene flakes is expected to significantly affect
      their sensing properties. Here we report an experimental investigation on the
      crystalline structure of graphene aimed at exploring the effects on the gas
      sensing properties. The morphology of graphene, prepared via Chemical Vapor
      Deposition (CVD), Liquid Phase Exfoliation (LPE) and Mechanical Exfoliation (ME),
      is inspected through Raman spectroscopy, Atomic Force Microscopy (AFM) and
      Scanning Electron Microscopy (SEM). CVD and LPE-graphene structures are found to
      be more defective with respect to ME-graphene. The defects are due to the jagged
      morphology of the films rather than originating from intrinsic disorder. The
      flatness of ME-graphene flakes, instead, explains the absence of defects.
      Chemiresistors based on the three different graphene preparation methods are
      subsequently exposed to NO2 in the concentration range 0.1-1.5 ppm (parts per
      million). The device performance is demonstrated to be strongly and unambiguously
      affected by the material structure: the less defective the material is, the
      higher the response rate is. In terms of signal variation, at 1.5 ppm, for
      instance, ME-graphene shows the highest value (5%) among the three materials.
      This study, comparing simultaneously graphene and sensors prepared via different
      routes, provides the first experimental evidence of the role played by the
      graphene level of defectiveness in the interaction with analytes. Moreover, these
      findings can pave the path for tailoring the sensor behavior as a function of
      graphene morphology.

PMID- 28443937
TI  - Supramolecular materials.
AB  - Molecular material properties depend upon the contacts between and the
      arrangement of the component parts, and therefore supramolecular chemistry has
      developed a highly important role in this area. This Tutorial Review, after
      briefly introducing the history of the field, discusses some of the most exciting
      and inspiring recent achievements, with special focus on soft materials,
      particularly gels and liquid crystals.

PMID- 28443938
TI  - Correction: Regioselective C8-metalation of N-phosphine tethered adenine
      derivatives via C8-H activation.
AB  - Correction for 'Regioselective C8-metalation of N-phosphine tethered adenine
      derivatives via C8-H activation' by D. Brackemeyer et al., Dalton Trans., 2017,
      DOI: 10.1039/c7dt00682a.

PMID- 28443939
TI  - Magnetic Fano resonance-induced second-harmonic generation enhancement in
      plasmonic metamolecule rings.
AB  - The "artificial magnetic" resonance in plasmonic metamolecules extends the
      potential application of magnetic resonance from terahertz to optical frequency
      bypassing the problem of magnetic response saturation by replacing the conduction
      current with the ring displacement current. So far, the magnetic Fano resonance
      induced nonlinearity enhancement in plasmonic metamolecule rings has not been
      reported. Here, we use the magnetic Fano resonance to enhance second-harmonic
      generation (SHG) in plasmonic metamolecule rings. In the spectra of the plasmonic
      metamolecule, an obvious Fano dip appears in the scattering cross section, while
      the dip does not appear in the absorption cross section. It indicates that at the
      Fano dip the radiative losses are suppressed, while the optical absorption
      efficiency is at a high level. The largely enhanced SHG signal is observed as the
      excitation wavelength is adjusted at the magnetic Fano dip of the plasmonic
      metamolecule rings with stable and tunable magnetic responses. We also compare
      the magnetic Fano dip with the electric case to show its advantages in enhancing
      the fundamental and second harmonic responses. Our research provides a new
      thought for enhancing optical nonlinear processes by magnetic modes.

PMID- 28443940
TI  - Facile processes for producing robust, transparent, conductive platinum nanofiber
      mats.
AB  - Mechanically robust freestanding platinum (Pt) nanofiber (NF) meshes are of great
      interest in applications where the corrosion resistance, malleability, and
      stability of a pure platinum structure must be combined with high surface area
      for catalysis. For photoelectrochemical applications, transparent electrodes are
      desirable. Several 1-dimensional (1D) Pt-based materials have been developed, but
      energy-intensive fabrication techniques and unsatisfactory performance have
      limited their practical implementation in next-generation photoelectrochemical
      applications. Here, we introduce relatively simple yet commercially-viable
      methods for creating robust, free-standing PtNF mats through combined
      electrospinning/solution blowing and electroplating steps. The PtNFs obtained by
      these processes exhibited outstanding low sheet resistance (Rs) values with
      reasonable transparency. In addition, the PtNFs were highly bendable and
      stretchable. Thus, the new methods and materials presented here hold great
      promise for creating mechanically robust and catalytically active transparent
      conducting films for diverse photoelectrochemical applications.

PMID- 28443941
TI  - Knowledge, attitudes and perceptions regarding lymphatic filariasis: study on
      systematic noncompliance with mass drug administration.
AB  - The aim of this study was to investigate the epidemiological characteristics,
      antigenic profile, perceptions, attitudes and practices of individuals who have
      been systematically non-compliant in mass drug administration (MDA) campaigns
      targeting lymphatic filariasis, in the municipality of Olinda, State of
      Pernambuco, Northeastern Brazil. A pretested questionnaire was used to obtain
      information on socioenvironmental demographics, perceptions of lymphatic
      filariasis and MDA, and reasons for systematic noncompliance with treatment. A
      rapid immunochromatographic test (ICT) was performed during the survey to screen
      for filariasis. It was found that the survey subjects knew about filariasis and
      MDA. Filariasis was identified as a disease (86.2%) and 74.4% associated it with
      the presence of swelling in the legs. About 80% knew about MDA, and the main
      source of information was healthcare workers (68.3%). For men the main reasons
      for systematic noncompliance with MDA were that "the individual had not received
      the medication" (p=0.03) and for women "the individual either feared experiencing
      adverse reactions". According to the ICT, the prevalence of lymphatic filariasis
      was 2%. The most important causes of systematic noncompliance were not receiving
      the drug and fear of side-effects. For successful implementation of MDA programs,
      good planning, educational campaigns promoting the benefits of MDA, adoption of
      measures to minimize the impact of adverse effects and improvement of drug
      distribution logistics are needed.

PMID- 28443942
TI  - Hemostatic disorders induced by skin contact with Lonomia obliqua (Lepidoptera,
      Saturniidae) caterpillars.
AB  - Patients envenomed by Lonomia sp caterpillars initially experience a mild burning
      pain, headache, nausea, vomiting, and skin and mucosal hemorrhages. Some patients
      can rapidly progress to a severe coagulopathy that presents as visceral or
      intracerebral hemorrhaging. We studied the hemostatic alterations that occurred
      in 14 patients who were envenomed by Lonomia obliqua in Southern Brazil and
      presented at the Hospital Sao Vicente de Paulo (Passo Fundo, RS), Brazil during
      the summers of 1993 and 1994 when Lonomia antivenom was not yet available for
      treatment. The patients were classified into to 4 clinical groups: 0 (two
      patients), I (eight patients), II (two patients), and III (two patients). The
      patients were admitted to the hospital between 4 hours and five days after
      contact with the caterpillars. In this study, the coagulation parameters of the
      patients were followed up for up to 172 hours after the accidents. The patients
      received no treatment with the exceptions of two patients who received blood
      transfusions and antifibrinolytic treatment. The observed abnormalities related
      to blood coagulation and fibrinolytic factors were similar regardless of the
      severity of the bleeding symptoms. These findings suggest that alterations in
      hemostatic parameters without thrombocytopenia are not predictors of the
      seriousness of such accidents. Thus, consumptive disorder and reactive
      fibrinolysis are not proportional to mild coagulopathy. Furthermore, these
      patients recovered. The hemostatic parameters of most of the patients normalized
      between 96 and 120 h after the accident.

PMID- 28443943
TI  - Multifocal nodular steatosis mimicking liver metastasis.

PMID- 28443944
TI  - The role of thromboelastometry in the assessment and treatment of coagulopathy in
      liver transplant patients.
AB  - Perioperative monitoring of coagulation is vital to assess bleeding risks,
      diagnose deficiencies associated with hemorrhage, and guide hemostatic therapy in
      major surgical procedures, such as liver transplantation. Routine static tests
      demand long turnaround time and do not assess platelet function; they are
      determined on plasma at a standard temperature of 37 degrees C; hence these tests
      are ill-suited for intraoperative use. In contrast, methods which evaluate the
      viscoelastic properties of whole blood, such as thromboelastogram and rotational
      thromboelastometry, provide rapid qualitative coagulation assessment and
      appropriate guidance for transfusion therapy. These are promising tools for the
      assessment and treatment of hyper- and hypocoagulable states associated with
      bleeding in liver transplantation. When combined with traditional tests and
      objective assessment of the surgical field, this information provides ideal
      guidance for transfusion strategies, with potential improvement of patient
      outcomes. RESUMO A monitorizacao perioperatoria da coagulacao e fundamental para
      estimar o risco de sangramento, diagnosticar deficiencias causadoras de
      hemorragia e guiar terapias hemostaticas durante procedimentos cirurgicos de
      grande porte, como o transplante hepatico. Os testes estaticos, comumente usados
      na pratica clinica, sao insatisfatorios no intraoperatorio, pois demandam tempo e
      nao avaliam a funcao plaquetaria; sao determinados no plasma e realizados em
      temperatura padrao de 37 degrees C. Os metodos que avaliam as propriedades
      viscoelasticas do sangue total, como o tromboelastograma e a tromboelastometria
      rotacional, podem suprir as deficiencias dos testes estaticos tradicionais, uma
      vez que permitem avaliar a coagulacao de forma rapida e qualitativa, guiando a
      terapia transfusional de forma adequada. A tromboelastometria rotacional mostrou
      se promissora na avaliacao e no tratamento de estados de hipercoagulacao e
      hipocoagulacao, associados a sangramento no transplante hepatico. Estas
      informacoes, combinadas com os testes tradicionais e uma avaliacao objetiva do
      campo cirurgico, promovem um cenario otimo para guiar as estrategias
      transfusionais e potencialmente melhorar o desfecho destes pacientes.

PMID- 28443945
TI  - [Sex and Gender Equity in Research: rationale for the SAGER guidelines and
      recommended use].
AB  - BACKGROUND: Sex and gender differences are often overlooked in research design,
      study implementation and scientific reporting, as well as in general science
      communication. This oversight limits the generalizability of research findings
      and their applicability to clinical practice, in particular for women but also
      for men. This article describes the rationale for an international set of
      guidelines to encourage a more systematic approach to the reporting of sex and
      gender in research across disciplines. METHODS: A panel of 13 experts
      representing nine countries developed the guidelines through a series of
      teleconferences, conference presentations and a 2-day workshop. An internet
      survey of 716 journal editors, scientists and other members of the international
      publishing community was conducted as well as a literature search on sex and
      gender policies in scientific publishing. RESULTS: The Sex and Gender Equity in
      Research (SAGER) guidelines are a comprehensive procedure for reporting of sex
      and gender information in study design, data analyses, results and interpretation
      of findings. CONCLUSIONS: The SAGER guidelines are designed primarily to guide
      authors in preparing their manuscripts, but they are also useful for editors, as
      gatekeepers of science, to integrate assessment of sex and gender into all
      manuscripts as an integral part of the editorial process.

PMID- 28443946
TI  - The production of knowledge and the strategies to incorporate results into the
      practice of nursing.

PMID- 28443947
TI  - Economic evaluation of human albumin use in patients with nephrotic syndrome in
      four Brazilian public hospitals: pharmacoeconomic study.
AB  - CONTEXT AND OBJECTIVE:: In 2004, the Brazilian National Health Surveillance
      Agency (Agencia Nacional de Vigilancia Sanitaria, ANVISA) published a resolution
      establishing guidelines for albumin use. Although the published data do not
      indicate any definitive conclusions about the benefits of albumin use in patients
      with nephrotic syndrome (NS), the guidelines recommend this procedure only in
      cases of edema that is refractory to use of diuretics. The aim here was to
      analyze albumin use among patients with nephrotic syndrome. DESIGN AND SETTING::
      Pharmacoeconomic study conducted in four large public referral hospitals for
      nephrology services in northeastern Brazil. METHOD:: Cost-effectiveness and cost
      utility economic evaluations were performed on a concurrent cohort of patients
      with nephrotic syndrome, who were divided into two groups according to compliance
      or noncompliance with the guidelines. Quality-of-life data were obtained from the
      SF36 and CHQ-PF50 questionnaires. RESULTS:: This study enrolled 109 patients (60%
      adults and 56% women); 41.3% were using albumin in accordance with the
      guidelines. The weight, diuresis and fluid balance parameters were more cost
      effective for patients who adhered to the guidelines. Regarding days of
      hospitalization avoided, the incremental ratio showed a daily cost of R$ 55.33,
      and guideline-compliant patients were hospitalized for five days or fewer. The
      quality of life improved by 8%, and savings of R$ 3,458.13/QALY (quality-adjusted
      life year) for the healthcare system were generated through guideline compliance.
      CONCLUSION:: The economic analyses of this study demonstrated that there were
      greater cost benefits for patients whose treatment followed the guidelines.

PMID- 28443948
TI  - Relapse of congenital thrombotic thrombocytopenic purpura, after spontaneous
      remission, in a second-trimester primigravida: case report and review of the
      literature.
AB  - CONTEXT: Thrombotic microangiopathy syndrome or thrombotic thrombocytopenic
      purpura-hemolytic uremic syndrome (TTP-HUS) describes distinct diseases sharing
      common pathological features: microangiopathic hemolytic anemia and
      thrombocytopenia, without any other apparent cause. CASE REPORT: An 18-year-old
      second-trimester primigravida presented with a history of fifteen days of intense
      weakness, followed by diarrhea over the past six days. She reported having had
      low platelets since childhood, but said that she had never had bleeding or
      menstrual abnormalities. Laboratory investigation showed anemia with
      schistocytes, thrombocytopenia and hypohaptoglobulinemia. Red blood cell
      concentrate and platelet transfusions were performed. The hypothesis of TTP or
      HUS was put forward and ADAMTS13 enzyme activity was investigated. The patient
      evolved with increasing platelet counts, even without specific treatment, and she
      was discharged. One month afterwards, she returned presenting weakness and
      swollen face and legs, which had developed one day earlier. The ADAMTS13 activity
      was less than 5%, without presence of autoantibodies. Regarding the two previous
      admissions (at 9 and 16 years of age), with similar clinical features, there was
      spontaneous remission on the first occasion and, on the second, the diagnosis of
      TTP was suspected and plasmapheresis was performed, but ADAMTS13 activity was not
      investigated. CONCLUSION: To date, this is the only report of congenital TTP with
      two spontaneous remissions in the literature This report reveals the importance
      of suspicion of this condition in the presence of microangiopathic hemolytic
      anemia and thrombocytopenia without any other apparent cause.

PMID- 28443949
TI  - Is reiki or prayer effective in relieving pain during hospitalization for
      cesarean? A systematic review and meta-analysis of randomized controlled trials.
AB  - CONTEXT AND OBJECTIVE:: This systematic review compared reiki and prayer with
      drug use for relieving pain during hospitalization for cesarean, given that the
      popularity of integrative medicine and spiritual healing has been increasing. It
      had the aim of evaluating whether reiki or prayer is effective in relieving pain
      during cesarean section. DESIGN AND SETTING:: Systematic review with meta
      analysis conducted at Botucatu Medical School, UNESP, Sao Paulo, Brazil.
      METHODS:: The following databases were searched up to March 2016: MEDLINE,
      Embase, LILACS and CENTRAL. Randomized controlled trials published in English or
      Portuguese were included in the review. Two reviewers independently screened
      eligible articles, extracted data and assessed the risk of bias. A GRADE table
      was produced to evaluate the risk of bias. RESULTS:: There was evidence with a
      high risk of bias showing a statistically significant decrease in pain score
      through use of reiki and prayer, in relation to the protocol group: mean
      difference = -1.68; 95% confidence interval: -1.92 to -1.43; P < 0.00001; I2 =
      92%. Furthermore, there was no statistically significant difference in heart rate
      or systolic or diastolic blood pressure. CONCLUSION:: Evidence with a high risk
      of bias suggested that reiki and prayer meditation might be associated with pain
      reduction.

PMID- 28443950
TI  - Chronic kidney disease - determinants of progression and cardiovascular risk.
      PROGREDIR cohort study: design and methods.
AB  - CONTEXT AND OBJECTIVE:: Chronic kidney disease (CKD) has become an important
      public health issue. The socioeconomic burden of renal replacement therapy (RRT)
      is very high, as is CKD-related cardiovascular mortality and morbidity.
      Preventive and therapeutic measures only have modest impact and more research is
      needed. Few cohort studies have been conducted on populations with CKD. Our aim
      was to establish a cohort that would include more advanced forms of CKD (stages 3
      and 4). Data collection was focused on renal and cardiovascular parameters.
      DESIGN AND SETTING:: Prospective cohort study; Sao Paulo, Brazil. METHODS::
      Recruitment took place in Hospital das Clinicas, Sao Paulo, from March 2012 to
      December 2013. Data relating to medical history, food-frequency questionnaire,
      anthropometry, laboratory work-up, calcium score, echocardiography, carotid
      intimal-medial thickness, pulse-wave velocity, retinography and heart rate
      variability were collected. A biobank including serum, plasma, post-oral glucose
      tolerance test serum and plasma, urine (morning and 24-hour urine) and DNA was
      established. RESULTS:: 454 participants (60% men and 50% diabetics) of mean age
      68 years were enrolled. Their mean estimated glomerular filtration rate-CKD
      Epidemiology Collaboration was 38 ml/min/1.73 m2. Follow-up is ongoing and the
      main outcomes are the start of RRT, cardiovascular events and death.
      CONCLUSIONS:: The PROGREDIR cohort is a promising prospective study that will
      allow better understanding of CKD determinants and validation of candidate
      biomarkers for the risks of CKD progression and mortality.

PMID- 28443951
TI  - Bariatric surgery in individuals with severe cognitive impairment: report of two
      cases.
AB  - CONTEXT: Bariatric surgery has become the gold-standard treatment for refractory
      morbid obesity. Obesity is frequently associated with certain syndromes that
      include coexisting cognitive deficits. However, the outcomes from bariatric
      surgery in this group of individuals remain incompletely determined. CASE REPORT:
      A 25-year-old male with Prader-Willi syndrome, whose intelligence quotient (IQ)
      was 54, was admitted with a body mass index (BMI) of 55 kg/m2, associated with
      glucose intolerance. He underwent the Scopinaro procedure for biliopancreatic
      diversion, with uneventful postoperative evolution, and presented a 55% loss of
      excess weight one year after the surgery, with resolution of glucose intolerance,
      and without any manifestation of protein-calorie malnutrition. A 28-year-old male
      with Down syndrome, whose IQ was 68, was admitted with BMI of 41.5 kg/m2,
      associated with hypertension. He underwent Roux-en-Y gastric bypass, with
      uneventful postoperative evolution. He presented a 90% loss of excess weight one
      year after the surgery, with resolution of the hypertension. CONCLUSION:
      Bariatric surgery among individuals with intellectual impairment is a
      controversial topic. There is a tendency among these individuals to present
      significant weight loss and comorbidity control, but less than what is observed
      in the general obese population. The severity of the intellectual impairment may
      be taken into consideration in the decision-making process regarding the most
      appropriate surgical technique. Bariatric surgery is feasible and safe among
      these individuals, but further research is necessary to deepen these
      observations.

PMID- 28443952
TI  - RESPONSE TO LETTER TO THE EDITOR: Boerhaave syndrome - case report.  A case of
      acute necrotizing esophagitis Black esophagus: new insights and multicenter
      international experience in 2014.

PMID- 28443953
TI  - Flexible bronchoscopy and mechanical ventilation in managing Mounier-Kuhn
      syndrome: a case report.
AB  - CONTEXT: Mounier-Kuhn syndrome is a rare congenital condition with distinct
      dilatation and diverticulation of the tracheal wall. The symptoms may vary and
      the treatment usually consists of support. CASE REPORT: The patient was a 60-year
      old male with recurrent hospital admission. He was admitted in this case due to
      dyspnea, cough and sputum production. An arterial blood sample revealed
      decompensated respiratory acidosis with moderate hypoxemia. A chest computed
      tomography (CT) scan showed dilatation of the trachea and bronchi, tracheal
      diverticula and bronchiectasis. Flexible bronchoscopy was performed, which
      revealed enlarged airways with expiratory collapse. Furthermore, orifices of
      tracheal diverticulosis were also detected. Non-invasive positive pressure
      ventilation (NPPV) was added, along with long-term oxygen therapy. At control
      visits, the patient's clinical and laboratory findings were found to have
      improved. CONCLUSION: Flexible bronchoscopy can be advocated for establishing the
      diagnosis and non-invasive mechanical ventilation can be used with a high success
      rate, for clinical wellbeing in Mounier-Kuhn syndrome.

PMID- 28443954
TI  - MMP-9 Levels and IMT of Carotid Arteries are Elevated in Obese Children and
      Adolescents Compared to Non-Obese.
AB  - BACKGROUND: Childhood obesity is associated with increased risk of
      atherosclerosis and cardiovascular disease in adulthood. Increased intima-media
      thickness (IMT) of the carotid artery is linked to the initiation and progression
      of the chronic inflammatory processes implicated in cardiovascular disease.
      Matrix metalloproteinase-9 (MMP-9) plays an important role in the degradation of
      the extracellular matrix and, consequently, in the development, morphogenesis,
      repair and remodeling of connective tissues. OBJECTIVES: (i) to determine and
      compare the concentrations of MMP-9, tissue inhibitor of metalloproteinase -1
      (TIMP-1), and MMP-9/TIMP-1 ratio in obese and non-obese children and adolescents;
      (ii) to investigate the association of these markers with common and internal IMT
      of carotid arteries. METHODS: Cross-sectional study involving 32 obese and 32 non
      obese (control) individuals between 8 - 18 years of age. RESULTS: Significantly
      (p < 0.05) higher values of MMP-9 concentration, as well as a higher MMP-9/TIMP-1
      ratio were detected in the obese group compared to control counterparts. Common
      and internal carotid IMT values were significantly higher (p < 0.001) in the
      obese group compared to the control group. Positive correlations were observed
      between the common carotid IMT values and MMP-9 concentrations as well as MMP
      9/TIMP-1 ratio. CONCLUSIONS: Our data demonstrate that obese children and
      adolescents present higher mean IMT values, plasma MMP-9 and MMP-9/TIMP-1 ratio
      compared to the non-obese. Thus, these findings indicate that this group presents
      a risk profile for early atherosclerosis.

PMID- 28443955
TI  - A Single Resistance Exercise Session Improves Aortic Endothelial Function in
      Hypertensive Rats.
AB  - BACKGROUND: Physical exercise is an important tool for the improvement of
      endothelial function. OBJECTIVE: To assess the effects of acute dynamic
      resistance exercise on the endothelial function of spontaneously hypertensive
      rats (SHR). METHODS: Ten minutes after exercise, the aorta was removed to
      evaluate the expression of endothelial nitric oxide synthase (eNOS),
      phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible
      nitric oxide synthase (iNOS) and to generate concentration-response curves to
      acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also
      performed with damaged endothelium and before and after NG-nitro-L-arginine
      methyl ester (L-NAME) and indomethacin administration. The maximal response
      (Emax) and the sensitivity (EC50) to these drugs were evaluated. RESULTS: ACh
      induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= 
      80 +/- 4.6%, p < 0.05) when compared to those of controls (Ct) (Emax = -50 +/-
      6.8%). The Emax to PHE was decreased following exercise conditions (95 +/- 7.9%,
      p < 0.05) when compared to control conditions (120 +/- 4.2%). This response was
      abolished after L-NAME administration or endothelial damage. In the presence of
      indomethacin, the aortic rings' reactivity to PHE was decreased in both groups
      (EC50= Ex -5.9 +/- 0.14 vs. Ct -6.6 +/- 0.33 log uM, p < 0.05 / Emax = Ex 9.5 +/-
      2.9 vs. Ct 17 +/- 6.2%, p < 0.05). Exercise did not alter the expression of eNOS
      and iNOS, but increased the level of p-eNOS. CONCLUSION: A single resistance
      exercise session improves endothelial function in hypertensive rats. This
      response seems to be mediated by increased NO production through eNOS activation.

PMID- 28443957
TI  - Major Depression and Acute Coronary Syndrome-Related Factors.
AB  - BACKGROUND: Major Depressive Disorder (MDD) is one of the most common mental
      illnesses in psychiatry, being considered a risk factor for Acute Coronary
      Syndrome (ACS). OBJECTIVE: To assess the prevalence of MDD in ACS patients, as
      well as to analyze associated factors through the interdependence of
      sociodemographic, lifestyle and clinical variables. METHODS: Observational,
      descriptive, cross-sectional, case-series study conducted on patients
      hospitalized consecutively at the coronary units of three public hospitals in the
      city of Rio de Janeiro over a 24-month period. All participants answered a
      standardized questionnaire requesting sociodemographic, lifestyle and clinical
      data, as well as a structured diagnostic interview for the DSM-IV regarding
      ongoing major depressive episodes. A general log-linear model of multivariate
      analysis was employed to assess association and interdependence with a
      significance level of 5%. RESULTS: Analysis of 356 patients (229 men), with an
      average and median age of 60 years (SD +/- 11.42, 27-89). We found an MDD point
      prevalence of 23%, and a significant association between MDD and gender, marital
      status, sedentary lifestyle, Killip classification, and MDD history. Controlling
      for gender, we found a statistically significant association between MDD and
      gender, age <= 60 years, sedentary lifestyle and MDD history. The log-linear
      model identified the variables MDD history, gender, sedentary lifestyle, and age
      <= 60 years as having the greatest association with MDD. CONCLUSION: Distinct
      approaches are required to diagnose and treat MDD in young women with ACS,
      history of MDD, sedentary lifestyle, and who are not in stable relationships.

PMID- 28443956
TI  - Prognostic Factors in Severe Chagasic Heart Failure.
AB  - BACKGROUND: Prognostic factors are extensively studied in heart failure; however,
      their role in severe Chagasic heart failure have not been established.
      OBJECTIVES: To identify the association of clinical and laboratory factors with
      the prognosis of severe Chagasic heart failure, as well as the association of
      these factors with mortality and survival in a 7.5-year follow-up. METHODS: 60
      patients with severe Chagasic heart failure were evaluated regarding the
      following variables: age, blood pressure, ejection fraction, serum sodium,
      creatinine, 6-minute walk test, non-sustained ventricular tachycardia, QRS width,
      indexed left atrial volume, and functional class. RESULTS: 53 (88.3%) patients
      died during follow-up, and 7 (11.7%) remained alive. Cumulative overall survival
      probability was approximately 11%. Non-sustained ventricular tachycardia (HR =
      2.11; 95% CI: 1.04 - 4.31; p<0.05) and indexed left atrial volume >= 72 mL/m2 (HR
      = 3.51; 95% CI: 1.63 - 7.52; p<0.05) were the only variables that remained as
      independent predictors of mortality. CONCLUSIONS: The presence of non-sustained
      ventricular tachycardia on Holter and indexed left atrial volume > 72 mL/m2 are
      independent predictors of mortality in severe Chagasic heart failure, with
      cumulative survival probability of only 11% in 7.5 years.

PMID- 28443958
TI  - Sensitivity, Specificity and Predictive Value of Heart Rate Variability Indices
      in Type 1 Diabetes Mellitus.
AB  - BACKGROUND: Heart rate variability (HRV) indices may detect autonomic changes
      with good diagnostic accuracy. Type diabetes mellitus (DM) individuals may have
      changes in autonomic modulation; however, studies of this nature in this
      population are still scarce. OBJECTIVE: To compare HRV indices between and assess
      their prognostic value by measurements of sensitivity, specificity and predictive
      values in young individuals with type 1 DM and healthy volunteers. METHODS: In
      this cross-sectional study, physical and clinical assessment was performed in 39
      young patients with type 1 DM and 43 young healthy controls. For HRV analysis,
      beat-to-beat heart rate variability was measured in dorsal decubitus, using a
      Polar S810i heart rate monitor, for 30 minutes. The following indices were
      calculated: SDNN, RMSSD, PNN50, TINN, RRTri, LF ms2, HF ms2, LF un, HF un, LF/HF,
      SD1, SD2, SD1/SD2, and ApEn. RESULTS: Type 1 DM subjects showed a decrease in
      sympathetic and parasympathetic activities, and overall variability of autonomic
      nervous system. The RMSSD, SDNN, PNN50, LF ms2, HF ms2, RRTri, SD1 and SD2
      indices showed greater diagnostic accuracy in discriminating diabetic from
      healthy individuals. CONCLUSION: Type 1 DM individuals have changes in autonomic
      modulation. The SDNN, RMSSD, PNN50, RRtri, LF ms2, HF ms2, SD1 and SD2 indices
      may be alternative tools to discriminate individuals with type 1 DM.

PMID- 28443959
TI  - Ankle-Brachial Index as a Predictor of Mortality in Hemodialysis: A 5-Year Cohort
      Study.
AB  - BACKGROUND: Abnormal ankle-brachial index (ABI) has been found to be a strong
      predictor of mortality in some hemodialysis populations in studies with
      relatively short periods of follow-up, lower than 2 years. OBJECTIVE: This study
      aimed to assess the predictive value of abnormal ABI as a risk factor for death
      among patients on maintenance hemodialysis after a 5-year follow-up. METHODS: A
      total of 478 patients on hemodialysis for at least 12 months were included in the
      study. ABI measurement was performed using a mercury column sphygmomanometer and
      portable Doppler. Patients were divided into 3 groups according to ABI (low:
      <0.9; normal: 0.9 to 1.3; and high: >1.3) and followed for a 60-month period.
      RESULTS: The prevalence rates of low, normal and high ABI were 26.8%, 64.6% and
      8.6%, respectively. The 5-year survival rate was lower in the groups with low ABI
      (44.1%, P<0.0001) and high ABI (60.8%, P= 0.025) than in the group with normal
      ABI (71.7%). Cox regression was used to evaluate the association between ABI and
      mortality, adjusting for potential confounders. Using normal ABI as reference, a
      low, but not a high ABI was found to be an independent risk factor for all-cause
      mortality (HR2.57; 95% CI, 1.84-3.57 and HR 1.62; 95% CI, 0.93-2.83,
      respectively). CONCLUSIONS: long-term survival rates of patients with either low
      or high ABI were lower than the one from those with normal ABI. However, after
      adjustment for potential confounders, only low ABI persisted as an independent
      risk factor for all-cause mortality among hemodialysis patients.

PMID- 28443961
TI  - Case 2/2017 - Cor Triatriatum, without Clinical Manifestation, in A 6-Year-Old
      Girl.

PMID- 28443960
TI  - Positioning about the Flexibility of Fasting for Lipid Profiling.

PMID- 28443962
TI  - Erratum.

PMID- 28443963
TI  - Aerobic Exercise and The Heart: Discussing Doses.

PMID- 28443964
TI  - Effects of Chronic Exercise on Endothelial Progenitor Cells and Microparticles in
      Professional Runners.
AB  - BACKGROUND: The effects of chronic exposure to exercise training on vascular
      biomarkers have been poorly explored. OBJECTIVE: Our study aimed to compare the
      amounts of endothelial progenitor cells (EPCs), and endothelial (EMP) and
      platelet (PMP) microparticles between professional runners and healthy controls.
      METHODS: Twenty-five half-marathon runners and 24 age- and gender-matched healthy
      controls were included in the study. EPCs (CD34+/KDR+, CD133+/KDR+, and
      CD34+/CD133+), EMP (CD51+) and PMP (CD42+/CD31+) were quantified by flow
      cytometry. All blood samples were obtained after 12 h of fasting and the athletes
      were encouraged to perform their routine exercises on the day before. RESULTS: As
      compared with controls, the CD34+/KDR+ EPCs (p=0.038) and CD133+/KDR+ EPCs
      (p=0.018) were increased, whereas CD34+/CD133+ EPCs were not different (p=0.51)
      in athletes. In addition, there was no difference in MPs levels between the
      groups. CONCLUSION: Chronic exposure to exercise in professional runners was
      associated with higher percentage of EPCs. Taking into account the similar number
      of MPs in athletes and controls, the study suggests a favorable effect of
      exercise on these vascular biomarkers.

PMID- 28443965
TI  - Prognosis Determinants after Cardioverter-Defibrillators Implantation in Brazil.

PMID- 28443966
TI  - Miniaturized Transcatheter Leadless Pacemaker in a Patient with Double Mechanical
      Prosthesis.

PMID- 28443967
TI  - Gramado Declaration: The Impact of 20 Years of Cardiovascular Prevention.

PMID- 28443968
TI  - Patient with Atrial Myxoma and Signs of Obstruction of the Left Ventricular
      Outflow Tract.

PMID- 28443969
TI  - ERRATUM.
AB  - [This corrects the article doi: 10.1590/1983-1447.2016.04.56945].

PMID- 28443970
TI  - Permanent education actions of nurse facilitators at a nursing education centre.
AB  - Objective: To identify actions of nurse facilitators of a permanent healthcare
      education centre of a teaching hospital. Methods: A single case study with a
      qualitative approach conducted with eight nurses from a hospital in the state of
      Rio Grande do Sul, Brazil. The data were generated through document analysis,
      systematic observation, and a focus group from April to September 2013. Results:
      The study produced the following categories: powerful strategies to promote
      permanent healthcare education actions from facilitating nurses and limitations
      for the development of these actions. Conclusions: The establishment of a
      permanent nursing education centre can trigger the Permanent education actions of
      nurses in teaching hospitals.

PMID- 28443971
TI  - Adherence to antiretroviral therapy by people living with HIV/AIDS in a
      municipality of Sao Paulo.
AB  - Objective: To assess adherence to antiretroviral drugs by people living with
      HIV/AIDS and identify its association with sociodemographic and clinical
      variables. Methods: Cross-sectional analytical study using a sociodemographic
      instrument and CEAT-HIV, with data collected in the period from 2014-2015.
      Results: A 75.0% was identified as having a good/proper adhesion. It was found
      that individuals between ages 40 and 59 (p = 0.029) and with morethan eight years
      of formal education (p = 0.043) had a higher level of compliance, as well as
      those diagnosed with HIV/AIDS for more than 10 years (p = 0.002), CD4 count >350
      cells/mm3 (p<0,001) and an undetectable viral load (p=0,025). Conclusion: In this
      study, a good adhesion between the subjects was identified and it was observed
      that individuals of older age, higher level of education, delayed diagnosis, high
      CD4 cell counts and undetectable viral load were associated with higher treatment
      adherence.

PMID- 28443972
TI  - Online information as support to the families of children and adolescents with
      chronic disease.
AB  - Objective: To describe the use of online information as support to families of
      children and adolescents with chronic disease. Methods: This is an integrative
      review conducted in August 2015, with an online search in the following
      databases: PubMed, Biblioteca Virtual em Saude, Cumulative Index to Nursing &
      Allied Health Literature, and Science Direct. Results: Twelve studies were
      selected from the 293 studies found in the databases. After analysis, the
      following two categories emerged: Potentialities of the use of online information
      by families of children and adolescents with chronic disease, and Weaknesses of
      the use of online information by families of children and adolescents with
      chronic disease. Conclusions: The internet offers a wide range of information
      that helps families manage the care of children and adolescents with chronic
      diseases, but it also has characteristics that need to be analysed.

PMID- 28443973
TI  - The experience of rural families who remain in halfway houses during cancer
      treatment.
AB  - Objective: to understand the experience of rural families who remain in halfway
      houses during the cancer treatment of an adult family member. Methods:
      qualitative research based on Symbolic Interaction and narrative research. Seven
      rural families participated in the study, 14 people staying in halfway houses in
      Santa Maria, Rio Grande do Sul, Brazil. The data obtained through interviews from
      November 2010 to May 2011 were analyzed with emphasis on content. Results: the
      three themes were: halfway houses as a reference for permanence during treatment,
      everyday life and living together in the halfway house. Conclusions: the
      experience was marked by the need to adapt to a context other than the rural one,
      with specific rules and routines, with discomforts and confrontations with urban
      culture characteristics and with what is experienced by other families who are
      also facing disease, which contributed to reframe the experience itself.

PMID- 28443974
TI  - Nurses' training in the use of a delirium screening tool.
AB  - Objective: To narrate the nurses' training experience in the implementation of a
      systematic delirium screening tool using the Confusion Assessment Method for
      Intensive Care Unit. Method: Experience report covering the steps of situation
      diagnosis, planning, staff training and evaluation of the tool's implementation
      between January and March 2013 with nurses in the ICU of a tertiary hospital in
      Sao Paulo. Results: The implementation of the assessment, using the Confusion
      Assessment Method for Intensive Care Unit, obtained significant nurse adhesion
      and became a service indicator. Final considerations: The experience has shown
      that this assessment allows the results of the work process to be analyzed and
      the consequent transformation of daily initiatives.

PMID- 28443975
TI  - Breastfeeding assessment instruments and their use in clinical practice.
AB  - Objectives: To identify breastfeeding assessment tools, their application in
      clinical practice, and their validation and cross-cultural adaptation. Method:
      This is an integrative review of literature obtained from six databases and an
      online library, conducted from August 2014 to December 2015, without a temporal
      delimitation. Results: We identified 19 assessment tools, of which 12 were
      validated and five were cross-culturally adapted. In terms of adaptation, the
      tools were used to assess the risk of early weaning (BAPT) and the
      perception/behaviour of mothers during nursing (BSES-SF and IIFAS). Conclusions:
      The identification of the available instruments and their indications for
      breastfeeding assessments can help health workers choose the ideal instrument,
      and qualify maternal and child care.

PMID- 28443976
TI  - Women's autonomy in the process of labour and childbirth: integrative literature
      review.
AB  - Objective: To identify the available evidence in scientific literature on
      healthcare practices that interfere with the autonomy of Brazilian women in the
      labour and delivery process. Method: The search for papers was conducted in the
      databases LILACS, Scopus and PubMed, between 1996 and 2015, according to a
      guiding question and exclusion criteria, resulting in the selection of 22 papers
      to compose the analytic body. Results: The main practices that favoured the
      exercise of women's autonomy were out-of-hospital care practices; care practices
      of support and comfort; and educational care practices. By contrast, the
      practices that limited autonomy were authoritarian care practices; standardised
      or routine care practices; care practices that intensify the painful sensation of
      childbirth; and impersonal and cold care practice. Conclusion: There was an
      alarming contrast between the daily healthcare routine and ministerial
      recommendations.

PMID- 28443977
TI  - Contributions of Paulo Freire to understanding the dialogic leadership exercise
      of nurses in the hospital setting.
AB  - Objective: To know the understanding of nurses regarding the exercise of dialogic
      leadership in the hospital setting, and the challenges of leadership. Methods:
      Qualitative and exploratory-descriptive study Thirty-five nurses of a mid-sized
      hospital in the city of Pelotas/RS participated in this study. Data were
      collected by means of semi-structured interviews, subsequently analysed using the
      operative proposal of Minayo. Results: The results led to the following
      categories: exercise of dialogic leadership and challenges in the exercise of
      dialogic leadership. Dialogic leadership is understood as being the nurses'
      ability to coordinate and organise the nursing team in horizontally-oriented
      relationships guided by dialogue. Regarding the challenges, the nurses stressed
      the lack of professional experience, and relationships of hierarchy and power.
      Final considerations: Leadership based on dialogue can facilitate the management
      of care, of the nursing team, and of health services.

PMID- 28443978
TI  - Characterisation of the vascular pathology in Sigmodon hispidus (Rodentia:
      Cricetidae) following experimental infection with Angiostrongylus costaricensis
      (Nematoda: Metastrongylidae).
AB  - BACKGROUND: Angiostrongylus costaricensis is a nematode that causes human
      abdominal angiostrongyliasis, a disease found mainly in Latin American countries
      and particularly in Brazil and Costa Rica. Its life cycle involves exploitation
      of both invertebrate and vertebrate hosts. Its natural reservoir is a vertebrate
      host, the cotton rat Sigmodon hispidus. The adult worms live in the ileo-colic
      branches of the upper mesenteric artery of S. hispidus, causing periarteritis.
      However, there is a lack of data on the development of vasculitis in the course
      of infection. OBJECTIVE: To describe the histopathology of vascular lesions in S.
      hispidus following infection with A. costaricensis. METHODS: Twenty-one S.
      hispidus were euthanised at 30, 50, 90 and 114 days post-infection (dpi), and
      guts and mesentery (including the cecal artery) were collected. Tissues were
      fixed in Carson's Millonig formalin, histologically processed for paraffin
      embedding, sectioned with a rotary microtome, and stained with hematoxylin-eosin,
      resorcin-fuchsin, Perls, Sirius Red (pH = 10.2), Congo Red, and Azan trichrome
      for brightfield microscopy analysis. FINDINGS: At 30 and 50 dpi, live eggs and
      larvae were present inside the vasa vasorum of the cecal artery, leading to
      eosinophil infiltrates throughout the vessel adventitia and promoting centripetal
      vasculitis with disruption of the elastic layers. Disease severity increased at
      90 and 114 dpi, when many worms had died and the intensity of the vascular
      lesions was greatest, with intimal alterations, thrombus formation, iron
      accumulation, and atherosclerosis. CONCLUSION: In addition to abdominal
      angiostrongyliasis, our data suggest that this model could be very useful for
      autoimune vasculitis and atherosclerosis studies.

PMID- 28443979
TI  - Experimental toxocariasis in BALB/c mice: relationship between parasite inoculum
      and the IgG immune response.
AB  - BALB/c mice were inoculated with 5-500 Toxocara canis infective eggs, and bled at
      15-120 days post infection (dpi) to evaluate the dynamics of IgG antibody
      response and larvae distribution. Positive results were observed in all occasions
      for every inoculum, and a direct proportional relationship between antibody
      detection and the parasitic load was observed. In samples collected at 60 dpi,
      detection of IgG was more intense, especially with the 50 and 500 egg doses;
      also, a correlation between antibody level and egg count was observed with these
      two inocula. At 120 dpi, a decrease in antibody titer was observed for all
      groups; and at the end of the experiment, larvae were recovered from carcass,
      liver and brain. In the liver, larvae were only found in mice inoculated with 500
      T. canis eggs. In carcasses, these were recovered in all groups, and the group
      inoculated with 50 eggs showed the highest percentage of larvae in the brain.

PMID- 28443980
TI  - Chagas disease: national survey of seroprevalence in children under five years of
      age conducted in 2008.
AB  - BACKGROUND: Since the early 1990s, programs to control Chagas disease in South
      America have focused on eradicating domiciliary Triatoma infestans, the main
      vector. Seroprevalence studies of the chagasic infection are included as part of
      the vector control programs; they are essential to assess the impact of vector
      control measures and to monitor the prevention of vector transmission. OBJECTIVE:
      To assess the interruption of domiciliary vector transmission of Chagas disease
      by T. infestans in Paraguay by evaluating the current state of transmission in
      rural areas. METHODS: A survey of seroprevalence of Chagas disease was carried
      out in a representative sample group of Paraguayans aged one to five years living
      in rural areas of Paraguay in 2008. Blood samples collected on filter paper from
      12,776 children were tested using an enzyme-linked immunosorbent assay. Children
      whose serology was positive or undetermined (n = 41) were recalled to donate a
      whole blood sample for retesting. Their homes were inspected for current
      triatomine infestation. Blood samples from their respective mothers were also
      collected and tested to check possible transmission of the disease by a
      congenital route. FINDINGS: A seroprevalence rate of 0.24% for Trypanosoma cruzi
      infection was detected in children under five years of age among the country's
      rural population. Our findings indicate that T. cruzi was transmitted to these
      children vertically. The total number of infected children, aged one to five
      years living in these departments, was estimated at 1,691 cases with an annual
      incidence of congenital transmission of 338 cases per year. MAIN CONCLUSION: We
      determined the impact of vector control in the transmission of T. cruzi,
      following uninterrupted vector control measures employed since 1999 in contiguous
      T. infestans-endemic areas of Paraguay, and this allowed us to estimate the
      degree of risk of congenital transmission in the country.

PMID- 28443981
TI  - Mapping the dengue scientific landscape worldwide: a bibliometric and network
      analysis.
AB  - BACKGROUND: Despite the current global trend of reduction in the morbidity and
      mortality of neglected diseases, dengue's incidence has increased and occurrence
      areas have expanded. Dengue also persists as a scientific and technological
      challenge since there is no effective treatment, vaccine, vector control or
      public health intervention. Combining bibliometrics and social network analysis
      methods can support the mapping of dengue research and development (R&D)
      activities worldwide. OBJECTIVES: The aim of this paper is to map the scientific
      scenario related to dengue research worldwide. METHODS: We use scientific
      publication data from Web of Science Core Collection - articles indexed in
      Science Citation Index Expanded (SCI-EXPANDED) - and combine bibliometrics and
      social network analysis techniques to identify the most relevant journals,
      scientific references, research areas, countries and research organisations in
      the dengue scientific landscape. FINDINGS: Our results show a significant
      increase of dengue publications over time; tropical medicine and virology as the
      most frequent research areas and biochemistry and molecular biology as the most
      central area in the network; USA and Brazil as the most productive countries; and
      Mahidol University and Fundacao Oswaldo Cruz as the main research organisations
      and the Centres for Disease Control and Prevention as the most central
      organisation in the collaboration network. MAIN CONCLUSIONS: Our findings can be
      used to strengthen a global knowledge platform guiding policy, planning and
      funding decisions as well as to providing directions to researchers and
      institutions. So that, by offering to the scientific community, policy makers and
      public health practitioners a mapping of the dengue scientific landscape, this
      paper has aimed to contribute to upcoming debates, decision-making and planning
      on dengue R&D and public health strategies worldwide.

PMID- 28443982
TI  - Enzyme-linked immunosorbent assay for diagnosis of Amphimerus spp. liver fluke
      infection in Humans.
AB  - BACKGROUND: Amphimerus spp. is a liver fluke that infects humans and domestic
      animals. It is highly prevalent in some Ecuadorian communities. Currently,
      diagnosis is based on the microscopic observation of eggs in faeces, but this has
      variable sensitivity. More sensitive methods are needed for diagnostic testing.
      OBJECTIVE: The main objective of this work was to develop an enzyme-linked
      immunosorbent assay (ELISA) using crude antigens from Amphimerus spp. adult worms
      to detect anti-Amphimerus IgG in human sera. METHODS: Crude somatic antigens were
      obtained from adult Amphimerus spp. worms. Human sera from 119 patients were
      tested: 48 from individuals with a confirmed Amphimerus spp. infection, 78 from
      non-infected Ecuadorians living in the endemic region, 60 from persons living in
      non-endemic areas (20 Ecuadorians, 20 Europeans, and 20 Africans), and 33 who had
      other parasitic and non-parasitic infections. PRINCIPAL FINDINGS: Results were
      analysed using the receiver-operator characteristic (ROC) curve analysis with an
      area under curve (AUC) value of 0.967. The accuracy of the ELISA was high. The
      sensitivity was 85.0% [95% confidence interval (CI): 80.3-89.7%] and the
      specificity was 71.0% (95% CI: 65.2-76.8%). Some cross reactivity was detected
      against Paragonimus mexicanus, Fasciola hepatica, Schistosomiasis, Taenia solium,
      Strongyloides stercoralis, Mansonella spp., and Vampirolepis nana. MAIN
      CONCLUSIONS: We have developed the first ELISA technique that detects anti
      Amphimerus IgG in human sera with good sensitivity, repeatability and
      reproducibility. However, more specific antigens are needed to further enhance
      performance of this assay. Regardless, this ELISA test could be useful for early
      diagnosis and prompt treatment of human Amphimerus spp. infections.

PMID- 28443983
TI  - Taenia sp. in human burial from Kan River, East Siberia.
AB  - We present an arhaeoparasitological analysis of a unique burial from the
      Neftprovod II burial ground in East Siberia, which dated from the Bronze Age.
      Analysis of a sediment sample from the sacral region of the pelvis revealed the
      presence of Taenia sp. eggs. Because uncooked animal tissue is the primary source
      of Taenia, this indicated that the individual was likely consuming raw or
      undercooked meat of roe deer, red deer, or elk infected with Taenia. This finding
      represents the oldest case of a human infected with Taenia sp. from Eastern
      Siberia and Russia.

PMID- 28443984
TI  - Antifungal activity of caspofungin in experimental infective endocarditis caused
      by Candida albicans.
AB  - BACKGROUND: Infective endocarditis is a disease characterised by heart valve
      lesions, which exhibit extracellular matrix proteins that act as a physical
      barrier to prevent the passage of antimicrobial agents. The genus Candida has
      acquired clinical importance given that it is increasingly being isolated from
      cases of nosocomial infections. OBJECTIVE: To evaluate the activity of
      caspofungin compared to that of liposomal amphotericin B against Candida albicans
      in experimental infective endocarditis. METHODS: Wistar rats underwent surgical
      intervention and infection with strains of C. albicans to develop infective
      endocarditis. Three groups were formed: the first group was treated with
      caspofungin, the second with liposomal amphotericin B, and the third received a
      placebo. In vitro sensitivity was first determined to further evaluate the effect
      of these treatments on a rat experimental model of endocarditis by
      semiquantitative culture of fibrinous vegetations and histological analysis.
      FINDINGS: Our semiquantitative culture of growing vegetation showed massive C.
      albicans colonisation in rats without treatment, whereas rats treated with
      caspofungin showed significantly reduced colonisation, which was similar to the
      results obtained with liposomal amphotericin B. CONCLUSIONS: The antifungal
      activity of caspofungin is similar to that of liposomal amphotericin B in an
      experimental model of infective endocarditis caused by C. albicans.

PMID- 28443985
TI  - Zika puzzle in Brazil: peculiar conditions of viral introduction and
      dissemination - A Review.
AB  - This article discusses the peculiar conditions that favoured the unexpected
      introduction of Zika virus into the poorest northeastern region of Brazil in
      2015, its speed of transmission to other Brazilian states, other Latin American
      countries and other regions, and the severity of related neurological disorders
      in newborns and adults. Contrasting with evidence that Zika had so far caused
      only mild cases in humans in the last six decades, the epidemiological scenario
      of this outbreak in Brazil indicates dramatic health effects: in 2015, an
      increase of 20-fold in notified cases of microcephaly and/or central nervous
      system (CNS) alterations suggestive of Zika congenital infection, followed by an
      exponential increase in 2016, with 2366 cumulative cases confirmed in the country
      by the end of December 2016. A significant increase in Guillain-Barre syndrome in
      adults has also been reported. Factors involved in viral dissemination, neural
      pathogenesis and routes of transmission in Brazil are examined, such as the role
      of social and environmental factors and the controversies involved in the
      hypothesis of antibody-dependent enhancement, to explain the incidence of
      congenital Zika syndrome in Brazil. Responses to the Zika outbreak and the
      development of new products are also discussed.

PMID- 28443986
TI  - Minimal inhibitory concentration distributions and epidemiological cutoff values
      of five antifungal agents against Sporothrix brasiliensis.
AB  - BACKGROUND: Sporothrix brasiliensis is the most virulent sporotrichosis agent.
      This species usually responds to antifungal drugs, but therapeutic failure can
      occur in some patients. Antifungal susceptibility tests have been performed on
      this species, but no clinical breakpoints (CBPs) are available. In this
      situation, minimal inhibitory concentration (MIC) distributions and
      epidemiological cutoff values (ECVs) support the detection of identification of
      resistant strains. OBJECTIVES: To study the MIC distributions of five antifungal
      drugs against S. brasiliensis and to propose tentative ECVs. METHODS: MICs of
      amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS),
      and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the
      Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS:
      The proposed ECV, in ug/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0,
      2.0, and 0.25, respectively. Percentages of wild-type strains in our population
      for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%,
      respectively. MAIN CONCLUSIONS: These ECVs will be useful to detect strains with
      resistance, to define CBPs, and to elaborate specific therapeutic guidelines for
      S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the
      emergence of resistant strains and ensure the therapeutic effectiveness of
      sporotrichosis.

PMID- 28443987
TI  - Seroprevalence of bactericidal antibodies against serogroup B and C Meningococci
      in a University Hospital.
AB  - Meningococcus serogroup B (MenB), clonal complex 32 (cc 32), was the Brazilian
      epidemic strain of meningococcal disease (MD) in the 1990's. Currently,
      meningococcus serogroup C (MenC), cc 103, is responsible for most of the cases of
      the disease in Brazil. The aim of this study was to investigate the
      seroprevalence of bactericidal antibody (SBA) against representative epidemic
      strains of MenC, (N753/00 strain, C:23:P1.22,14-6, cc103) and MenB, (Cu385/83
      strain, B:4,7:P1.15,19, cc32) in students and employees of a university hospital
      in the State of Rio Grande do Sul (RS, Brazil). A second MenC strain (N79/96,
      C:2b:P1.5-2,10, cc 8) was used as a prototype strain of Rio de Janeiro's outbreak
      that occurred in the 1990's. Our previous study showed a 9% rate of asymptomatic
      carriers in these same individuals. A second goal was to compare the SBA
      prevalence in meningococcal carriers and non-carriers. Fifty-nine percent of the
      studied population showed protective levels of SBA titers (log2>=2) against at
      least one of the three strains. About 40% of the individuals had protective
      levels of SBA against N753/00 and Cu385/83 strains. Nonetheless, only 22% of the
      individuals showed protective levels against N79/96 strain. Significantly higher
      antibody levels were seen in carriers compared to non-carriers (P<=0.009). This
      study showed that, similar to other States in Brazil, a MenC (23:P1.22,14-6,
      cc103) strain with epidemic potential is circulating in this hospital. Close
      control by the Epidemiological Surveillance Agency of RS of the number of cases
      of MD caused by MenC strains in the State is recommended to prevent a new disease
      outbreak.

PMID- 28443988
TI  - Efficacy of minimally invasive tonsil surgery for treatment of obstructive sleep
      apnea-hypopnea syndrome in children.
AB  - This study aimed to investigate the efficacy of minimally invasive tonsil surgery
      for the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) in
      children. Tonsil ablation or turbinate reduction was performed on 49 pediatric
      patients with OSAHS by minimally invasive tonsil surgery. In order to evaluate
      the efficacy of surgery, a comparison was conducted between pre-operation and
      post-operation data in terms of the symptoms, signs and polysomnography test.
      Total effectiveness rate of the surgery was 83.7%. Subgroup analysis was also
      performed based on the severity of their conditions: mild, moderate, and severe
      groups had an effectiveness rate of 90.0, 88.9, and 66.7%, respectively
      (Hc=6.665, P<0.05). Postoperatively, the apnea-hypopnea index, the minimum oxygen
      saturation (SaO2), and corresponding symptoms improved compared to pre-operation
      conditions (P<0.05). Minimally invasive tonsil surgery was a safe and effective
      method for treating OSAHS in children.

PMID- 28443989
TI  - Diagnostic and prognostic value of procalcitonin for early intracranial infection
      after craniotomy.
AB  - Intracranial infection is a common clinical complication after craniotomy. We
      aimed to explore the diagnostic and prognostic value of dynamic changing
      procalcitonin (PCT) in early intracranial infection after craniotomy. A
      prospective study was performed on 93 patients suspected of intracranial
      infection after craniotomy. Routine peripheral venous blood was collected on the
      day of admission, and C reactive protein (CRP) and PCT levels were measured.
      Cerebrospinal fluid (CSF) was collected for routine biochemical, PCT and culture
      assessment. Serum and CSF analysis continued on days 1, 2, 3, 5, 7, 9, and 11.
      The patients were divided into intracranial infection group and non-intracranial
      infection group; intracranial infection group was further divided into infection
      controlled group and infection uncontrolled group. Thirty-five patients were
      confirmed with intracranial infection after craniotomy according to the
      diagnostic criteria. The serum and cerebrospinal fluid PCT levels in the infected
      group were significantly higher than the non-infected group on day 1 (P<0.05,
      P<0.01). The area under curve of receiver operating characteristics was 0.803 for
      CSF PCT in diagnosing intracranial infection. The diagnostic sensitivity and
      specificity of CSF PCT was superior to other indicators. The serum and CSF PCT
      levels have potential value in the early diagnosis of intracranial infection
      after craniotomy. Since CSF PCT levels have higher sensitivity and specificity,
      dynamic changes in this parameter could be used for early detection of
      intracranial infection after craniotomy, combined with other biochemical
      indicators.

PMID- 28443990
TI  - MicroRNA-340-5p modulates cisplatin resistance by targeting LPAATbeta in
      osteosarcoma.
AB  - MicroRNAs (miRNAs) play an important role in drug resistance and modulate the
      efficiency of chemotherapy. A recent study indicated that miR-340 functions as a
      tumor suppressor in various types of cancer. However, the role of miR-340 in
      chemotherapy has not been reported yet. In this study, we found that miR-340
      enhanced cisplatin (CDDP)-induced cell death. Induction of miR-340-5p expression
      decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63
      and Saos-2 cells. Moreover, miR-340-5p decreased the accumulation of MRP1 and
      MDR1. We further explored the mechanism underlying the promoting effects of miR
      340-5p on CDDP-induced cell death. We identified a potential target of miR-340 in
      the 3' untranslated region of lysophosphatidic acid acyltransferase (LPAATbeta)
      using the online program Targetscan (http://www.microrna.org). Luciferase
      reporter assays showed that miR-340 binds to the 3'UTR of LPAATbeta. Enforced
      expression of miR-340-5p decreased the accumulation of LPAATbeta in both MG-63
      and Saos-2 cells. Silencing LPAATbeta decreased the IC50 of CDDP and increased
      the apoptosis of CDDP-resistant MG-63 and Saos-2 cells, which is consistent with
      the effect of miR-340-5p on CDDP-induced cell death. Moreover, induced expression
      of LPAATbeta compromised the effects of miR-340-5p on CDDP-induced cell death and
      accumulation of MRP1 and MDR1. Taken together, our data indicated that miR-340-5p
      enhanced the sensitivity to CDDP by targeting LPAATbeta.

PMID- 28443991
TI  - Risk assessment and incidence of falls in adult hospitalized patients.
AB  - OBJECTIVES: assess the risk of falls in adult hospitalized patients and verify
      the incidence of the event in this environment. METHOD: cohort study, with
      approval by the Research Ethics Committee, which monitored 831 patients
      hospitalized at a university hospital. The Morse Fall Scale (MFS) was used to
      assess the risk and patients with high risk (>=45 points) were considered exposed
      to falls. RESULTS: the mean MFS score was 39.4 (+/-19.4) points. Between the
      first and the final assessment, the score increased by 4.6%. The first assessment
      score presented a strong and positive correlation with the final assessment score
      (r=0.810; p=0.000). CONCLUSION: the higher the risk score for falls when the
      patient is admitted, the higher the score at the end of the hospitalization
      period and vice-versa. The incidence rate corresponded to 1.68% with a higher
      percentage of patients classified at high risk of falls.

PMID- 28443992
TI  - Educational interventions for knowledge on the disease, treatment adherence and
      control of diabetes mellitus.
AB  - OBJECTIVE: to assess the effect of educational interventions for knowledge on the
      disease, medication treatment adherence and glycemic control of diabetes mellitus
      patients. METHOD: evaluation research with "before and after" design, developed
      in a sample of 82 type 2 diabetes mellitus patients. To collect the data, the
      Brazilian version of the Diabetes Knowledge Scale (DKN-A), the Measure of
      Adherence to Treatments and the electronic system at the place of study were
      used. The data were collected before and after the end of the educational
      interventions. The educational activities were developed within 12 months,
      mediated by the Diabetes Conversation Maps, using the Cognitive Social Theory to
      conduct the interventions. RESULTS: the knowledge on the disease (p<0.001), the
      medication treatment (oral antidiabetics) (p=0.0318) and the glycated hemoglobin
      rates (p=0.0321) improved significantly. CONCLUSION: the educational
      interventions seem to have positively contributed to the participants' knowledge
      about diabetes mellitus, the medication treatment adherence and the glycated
      hemoglobin rates.

PMID- 28443993
TI  - Work accidents and self-esteem of nursing professional in hospital settings.
AB  - OBJECTIVE: to analyze the occurrence of work accidents and the self-esteem of
      nurses in hospitals of a municipality of Minas Gerais. METHOD: descriptive
      analytical and cross-sectional study developed with 393 nursing professionals
      from three hospitals of a municipality in southern Minas Gerais. The Rosenberg
      Self-Esteem Scale and a questionnaire to characterize the population and work
      accidents were used for data collection. Data analysis was performed using
      Person's chi-squared test, Fisher's exact test, Cronbach's alpha, odds ratio and
      logistic regression. RESULTS: of the professionals studied, 15% had suffered an
      accident at work and 70.2% presented high self-esteem. Through the analysis, it
      was observed that smoking, religious belief and an outstanding event in the
      career were significantly associated with work accidents. In relation to self
      esteem, family income, length of time working in the profession and an
      outstanding event in the career presented significant associations. CONCLUSION:
      factors such as smoking, religious belief, family income, length of time working
      in the profession and an outstanding event in the career can cause professionals
      to have accidents and/or cause changes in self-esteem, which can compromise their
      physical and mental health and their quality of life and work.

PMID- 28443994
TI  - Relationship between psychosocial stress dimensions and salivary cortisol in
      military police officers.
AB  - OBJECTIVE: to analyze the relationship between psychosocial stress dimensions and
      salivary cortisol in military police officers. METHOD: cross-sectional and
      analytical study with 134 military police officers. The Effort-Reward Imbalance
      (ERI) Model scale has been used to assess psychosocial stress. Salivary cortisol
      was collected in three samples. The following tests were used: Student's t-test,
      Mann-Whitney, ANOVA, Bonferroni, Kruskal-Wallis and Dunn. Pearson and Spearman
      correlation methods were used, as well as multiple linear regression. Cortisol at
      night showed an ascending statistical association with the psychosocial reward
      (p=0.004) and a descending association with the effort-impairment scores
      (p=0.017). Being part of the Special Tactical Operations Group (GATE) and the
      diastolic blood pressure explained 13.5% of the variation in cortisol levels on
      waking up. The sectors GATE, Special Patrol of the Elite Squad of the Military
      Police and Motorcyclists explained 21.9% of the variation in cortisol levels 30
      minute after awakening. The variables GATE sector and Effort Dimension explained
      27.7% of the variation in cortisol levels at night. CONCLUSION: it was evidenced
      that salivary cortisol variation was influenced by individual, labor and
      psychosocial variables.

PMID- 28443995
TI  - Quality of life of people living with HIV/AIDS: temporal, socio-demographic and
      perceived health relationship.
AB  - OBJECTIVE: to analyze the quality of life of people living with HIV/AIDS and its
      relationship with sociodemographic variables, health satisfaction and time since
      diagnosis. METHOD: quantitative, cross-sectional study with a sample of 100 HIV
      positive people monitored in a specialized service in southeastern Brazil.
      Sociodemographic and health forms were applied, followed by the WHOQOL-HIV BREF,
      a short form instrument validated to evaluate the quality of life. Descriptive
      and inferential statistical analysis was performed. RESULTS: the perception of
      quality of life was intermediate in all quality of life domains. A relationship
      was identified between greater satisfaction with health and better quality of
      life, as well as statistically significant differences among the dimensions of
      quality of life according to gender, employment status, family income, personal
      income, religious beliefs and time since diagnosis. CONCLUSIONS: the time since
      the diagnosis of HIV infection enables reconfigurations in the perception of
      quality of life, while spirituality and social relationships can assist in coping
      with living with this disease.

PMID- 28443996
TI  - ?

PMID- 28443997
TI  - [Maternal mental health: a risk factor affecting the social and emotional well
      being of Mexican children].
AB  - Objectives: To estimate the prevalence of symptoms of depression and anxiety in
      mothers from three population areas in the state of San Luis Potosi, Mexico, and
      to analyze the association between these symptoms and the emotional health of
      their children. Methods: Assessment was conducted on 173 mother-child pairs from
      three different population areas: urban, rural, and indigenous rural. Women's
      symptoms of depression and anxiety were evaluated, together with their children's
      behavioral problems. Results: A high prevalence of symptoms of depression and
      anxiety was found in the three areas included. The proportion of depressive
      symptoms was highest in the urban and rural areas (38.7% and 38.6%,
      respectively). The highest prevalence of anxiety symptoms was observed in the
      rural area (31.8%). The strongest association between maternal anxiety and
      maternal depression was found in the rural area (odds ratio [OR] = 11.0; 95% CI:
      1.3-95.5). The indigenous rural area showed the highest prevalence of behavioral
      problems among children (61%). An association between such problems and maternal
      anxiety (OR = 2.2; 95% CI: 1.1-4.3) and maternal depression (OR = 2.5; 95% CI:
      1.3-4.6) was noted. Conclusions: The mental health of mothers can put the social
      and emotional well-being of their children at risk. This conclusion is supported
      by the findings, namely high prevalences and an association between symptoms of
      anxiety and depression and behavioral problems. In Mexico, reliable information
      on the mental health status of women and children in the three population areas
      studied is needed in order to implement measures towards expanding coverage for
      evaluation and prevention.

PMID- 28443998
TI  - [Detection of stool antigens of Echinococcus granulosus in dogs belonging to
      slaughterhouse workers and offal merchants in Metropolitan Lima].
AB  - Objective: To demonstrate the presence of Echinoccocus granulosus in the
      definitive host in the city of Lima, Peru, by detecting parasite antigens in the
      stool of dogs belonging to offal handlers and merchants in authorized
      slaughterhouses in Metropolitan Lima. Methods: Stool samples were collected from
      58 dogs and examined using the coproELISA technique for the detection of
      secretory/excretory antigens of E. granulosus. A survey was conducted to obtain
      information on pet feeding and handling practices. Results: Positivity to E.
      granulosus was detected in 13.8% (8/58) of the dogs. In 27.8% (5/18) of the
      homes, at least one animal showed positivity, and in families that had more than
      four dogs the chances of finding positivity in at least one dog were higher (P <
      0.05). In all homes where at least one dog tested positive the pets were fed on
      offal. Of study participants, 94.4% (17) knew nothing about the routes of
      transmission of hydatid disease. Conclusions: Results show the presence of
      definitive hosts in the urban area of Lima and underscore the need to more widely
      disseminate practices for the prevention of parasite transmission.

PMID- 28443999
TI  - First reported enterovirus D68 infection in pediatric patients from the Caribbean
      region: evidence of spread from the U.S. outbreak.
AB  - The 2014 enterovirus D68 (EV-D68) outbreak in the United States raised concerns
      about the introduction of the virus in the Caribbean region. The objective of
      this study was to provide rapid evidence of the introduction of EV-D68 strains in
      the Caribbean region during the 2014 outbreak in the United States, using a
      relatively simple phylogenetic approach. From October 2014 to May 2015, four EV
      D68 cases from two countries (Bermuda and Dominica) were detected at the regional
      referral laboratory at the Caribbean Public Health Agency (Port of Spain,
      Trinidad and Tobago) based on molecular testing of respiratory specimens. All
      cases were children presenting to hospitals with moderate respiratory distress.
      No cases of acute flaccid paralysis were detected. Phylogenetic analysis of the
      Caribbean strains showed more than 99% similarity with the 2014 U.S.-outbreak
      strain, providing evidence of the introduction and circulation of the virus in
      the region.

PMID- 28444000
TI  - Strengthening the regulatory system through the implementation and use of a
      quality management system.
AB  - Quality management systems (QMS), based on ISO 9001 requirements, are applicable
      to government service organizations such as Health Canada's Biologics and Genetic
      Therapies Directorate (BGTD). This communication presents the process that the
      BGTD followed since the early 2000s to implement a quality management system and
      describes how the regulatory system was improved as a result of this project.
      BGTD undertook the implementation of a quality management system based on ISO
      9001 and containing aspects of ISO 17025 with the goal of strengthening the
      regulatory system through improvements in the people, processes, and services of
      the organization. We discuss the strategy used by BGTD to implement the QMS and
      the benefits that were realized from the various stages of implementation. The
      eight quality principals upon which the QMS standards of the ISO 9000 series are
      based were used by senior management as a framework to guide QMS implementation.

PMID- 28444001
TI  - Birth weight and risk of childhood solid tumors in Brazil: a record linkage
      between population-based data sets.
AB  - Objective: To analyze the relationship between the development of childhood solid
      tumors and 1) birth weight and 2) fetal growth, using two Brazilian population
      based data sets. Methods: A case-cohort study was performed using two population
      based data sets, and linkage between the Live Birth Information System (Sistema
      de Informacao sobre Nascidos Vivos, SINASC) and 14 population-based cancer
      registries (PBCRs) was established. Four controls per case were chosen randomly
      from the SINASC data set. Tumors were classified as central nervous system (CNS),
      non-CNS embryonal, and other tumors ("miscellaneous"). Adjustments were made for
      potential confounders (maternal age, mode of delivery, maternal education, birth
      order, gestational age, sex, and geographic region). Odds ratios (ORs) with 95%
      confidence intervals (CIs) were computed using unconditional logistic regression
      analysis. Results: In a trend analysis, for every 500 g of additional birth
      weight, the crude OR was 1.12 (CI: 1.00-1.24) and the adjusted OR was 1.02 (CI:
      0.90-1.16) for all tumors. For every 1 000 g of additional birth weight, the
      crude OR was 1.25 (CI: 1.00-1.55) and the adjusted OR was 1.04 (CI: 0.82-1.34)
      for all tumors. Among children diagnosed after reaching the age of 3 years, in
      the miscellaneous tumor category, the OR was significantly increased for every
      additional 500 g and 1 000 g of birth weight. Conclusions: The study data
      suggested that increased birth weight was associated with childhood solid tumor
      development, especially among children more than 3 years old with "miscellaneous"
      tumors.

PMID- 28444002
TI  - [Analysis of proximate determinants and impact of type of employment on fertility
      in peruvian women].
AB  - Objective: To estimate the predictive capacity of proximate determinants and type
      of employment with respect to reduced fertility in Peruvian women of childbearing
      age. Methods: Secondary analysis of Peru's Demographic and Family Health Survey
      (ENDES) for 2014. The sample consisted of 20 396 women aged 15 to 49 years who
      had been sexually active during the four-week period immediately before the
      interview. The dependent variable was the total number of live births, and the
      main independent variables were type of employment, ideal number of offspring,
      highest educational level attained, and wealth quintile. Odds ratios (OR) were
      used to estimate the strength of the associations between proximate determinants
      and type of employment on the one hand and fertility on the other in logistic
      regression models. The goodness of fit of the models was estimated using the
      Hosmer-Lemeshow test and its discriminatory capacity, based on receiver operating
      characteristic curves. Results: Desired fertility (2.5 children per woman) was
      higher than actual fertility (2.1). The factors most strongly associated with
      reduced fertility were higher educational attainment (OR = 0.03; 95% CI: 0.02
      0.04); ideal number of offspring between 0 and 2 (OR = 0.13; 95% CI: 0.11-0.15);
      and dependent employment (OR = 0.31; 95% CI: 0.28-0.34). The models' areas under
      the curve were 0.908 (95% CI: 0.898-0.917) and 0.91 (95% CI: 0.891-0.928),
      respectively. Conclusion: Older age at first sexual intercourse and older age
      when first married (direct determinants) delay childbearing, whereas higher
      educational level and belonging to the highest wealth quintile (indirect
      determinants) indicate greater economic autonomy, which, in turn, is associated
      with low fertility. Similarly, the more dependent the work, the lower the
      fertility of the women surveyed.

PMID- 28444003
TI  - Species abundance and temporal variation of arbovirus vectors in Brownsville,
      Texas.
AB  - The recent outbreaks of the dengue fever and West Nile viruses and the looming
      threats of the Zika and chikungunya viruses highlight the importance of
      establishing effective, proactive arboviral surveillance in communities at high
      risk of transmission, such as those on the Texas-Mexico border. Currently, there
      are no approved human vaccines available for these mosquito-borne diseases, so
      entomological control and case management are the only known methods for
      decreasing disease incidence. The principal vectors, which include Culex
      quinquefasciatus, Aedes aegypti, and Ae. Albopictus, all have an established
      presence in South Texas. The public health response to most arbovirus outbreaks
      in the region has been reactionary rather than proactive. However, after the 2005
      dengue outbreak and subsequent fatality, the City of Brownsville Public Health
      Department began collecting data on mosquito vector abundance and incidence. The
      objective of this study was to describe the various species of mosquitoes found
      in vector surveillance in Brownsville, Texas, during 2009-2013; quantify their
      prevalence; and identify any associations with temporal or weather-related
      variations. The results confirm a significant mosquito population in Brownsville
      in late winter months, indicating a high risk of arbovirus transmission in South
      Texas year-round, and not just until November, previously considered the end date
      of arbovirus season by state health services. The data from Brownsville's
      surveillance program can help characterize local vector ecology and facilitate
      more proactive mitigation of future arboviral threats in South Texas.

PMID- 28444004
TI  - Relation between HIV status, risky sexual behavior, and mental health in an MSM
      sample from three Chilean cities.
AB  - Objective: To explore the association among HIV status; negative psychological
      symptoms (anxiety, depression, and hostility); and risky sexual behaviors
      (multiple sexual partners and unprotected sexual intercourse) in a Chilean sample
      of men who have sex with men (MSM). Methods: This study had a cross-sectional
      design and a sample of 325 MSM whose ages ranged from 18 to 64 years (mean: 30.8;
      standard deviation: 9.8). Association tests (chi-squared) and group mean
      comparisons (Student's t-tests and F-tests) were performed. Results: No
      statistically significant differences were found for condom use or for the number
      of sexual partners between HIV-positive men and those who are not infected. In
      both groups, about 50% reported sexual encounters without condom use in the past
      six months. There were statistically significant differences in symptoms
      associated with depression between the two groups. Conclusions: These results
      reveal the need to strengthen messages about the importance of condom use, as the
      only way to prevent HIV, and as a means of preventing HIV infection and
      reinfection, in national prevention and self-care programs for sexually active
      subjects. More studies are needed in Latin America to advance HIV prevention
      efforts for the MSM population. The data generated by this study can be used to
      inform the development of HIV prevention programming strategies and interventions
      targeting the MSM population in Latin America.

PMID- 28444005
TI  - Promoting and regulating generic medicines: Brazil in comparative perspective.
AB  - Promoting the use of generic drugs can constitute a core instrument for
      countries' national pharmaceutical policies, one that reduces drug expenditure
      while expanding health care access. Despite the potential importance of such
      policy measures and the differences among national practices, scholars embarking
      on comparative analysis lack a roadmap for determining which dimensions of
      generic drug policy to assess and compare. This report fills that gap by
      considering national rules and regulations across four dimensions deemed crucial
      to any evaluation: demonstrated therapeutic equivalence; pharmaceutical packaging
      and labeling; drug prescription; and drug substitution. Furthermore, this report
      examines how the diverse interests of public and private sector stakeholders
      might shape generic drug policy and its implementation. To illustrate the
      challenges and conflicts behind policy development and implementation, this
      report focuses on the case of Brazil.

PMID- 28444006
TI  - Scale-up of collaborative TB/HIV activities in Guyana.
AB  - Objective: To assess scale-up of recommended tuberculosis (TB)/HIV activities in
      Guyana and to identify specific strategies for further expansion. Methods:
      Medical records and clinic registers were reviewed at nine TB clinics and 10 HIV
      clinics. At TB clinics, data were collected on HIV testing and antiretroviral
      therapy (ART) for patients with TB/HIV; at HIV clinics, data were collected on
      intensified case finding (ICF), tuberculin skin test (TST) results, and provision
      of isoniazid preventive therapy (IPT). Results: At TB clinics, among 461 patients
      newly diagnosed with TB, 419 (90.9%) had a known HIV status and 121 (28.9%) were
      HIV-infected. Among the 63 patients with TB/HIV, 33 (52.4%) received ART. Among
      the 45 patients with TB/HIV for whom dates of HIV diagnosis were available, 38
      (84.4%) individuals knew their HIV status prior to TB diagnosis. At HIV clinics,
      among 127 patients eligible to receive a TST, 87 (68.5%) received a TST, 66
      (75.9%) had a TST result, seven (10.6%) had a newly positive result, two had a
      previously positive result, and six of nine patients with positive results
      (66.7%) received IPT. ICF could not be assessed because of incomplete or
      discrepant documentation. Conclusions: An in-depth evaluation of TB/HIV
      activities successfully identified areas of success and remaining challenges. At
      TB clinics, HIV testing rates are high; further scale-up of ART for persons with
      TB/HIV is needed. At HIV clinics, use of TST to focus IPT is a feasible and
      efficient strategy; improving rates of annual TST screening will allow for
      further expansion of IPT.

PMID- 28444007
TI  - Prevalence of risk factors for noncommunicable diseases in an indigenous
      community in Santiago Atitlan, Guatemala.
AB  - Objective: To describe the prevalence of noncommunicable disease (NCD) risk
      factors and assess knowledge of those risk factors in the indigenous community of
      Santiago Atitlan in Guatemala, a lower-middle income country. Methods: A
      population-based, cross-sectional study was conducted using a modified version of
      the World Health Organization's STEPS protocol. Adults aged 20-65 years were
      surveyed regarding demographics and NCD risk factors, and the survey was followed
      by anthropometric and biochemical measurements. Results: Out of 501 screened
      individuals, 350 respondents were enrolled. The mean age was 36.7 years, and
      72.3% were women. Over 90% reported earning less than US$ 65 per month. Almost
      80% were stunted. Among women, 37.3% were obese and over three-quarters had
      central obesity. Over three-quarters of the entire group had dyslipidemia and
      18.3% had hypertension, but only 3.0% had diabetes. Overall, 36.0% of
      participants met criteria for metabolic syndrome. There was no significant
      association between participants' education and NCD risk factors except for an
      inverse association with obesity by percent body fat. Conclusions: Santiago
      Atitlan is a rural, indigenous Guatemalan community with high rates of poverty
      and stunting coexisting alongside high rates of obesity, particularly among
      women. Additionally, high rates of hypertension and dyslipidemia were found, but
      a low rate of diabetes mellitus. Knowledge of NCDs and their risk factors was
      low, suggesting that educational interventions may be a high-yield, low-cost
      approach to combating NCDs in this community.

PMID- 28444008
TI  - From guidelines to local realities: evaluation of oral rehydration therapy and
      zinc supplementation in Guatemala.
AB  - Objective: Diarrhea remains a leading cause of morbidity and mortality for
      children in low- and middle-income countries throughout the Americas. The World
      Health Organization (WHO) has developed guidelines on incorporating zinc
      supplementation (ZS) with traditional oral rehydration therapy (ORT) in order to
      shorten the duration of diarrheal episodes and to reduce poor health outcomes.
      Guatemala adopted these guidelines in 2011, but they have not yet been fully
      implemented at the community level. The objectives of this study were: (1) to co
      design an ORT/ZS training program for community members with local health
      promoters that is appropriate to the local context and (2) to understand how
      attitudes and behaviors of community members changed after receiving training
      from the study promoters. Methods: In an observational study, community health
      promoters in rural Guatemala were trained according to WHO guidelines, and they
      worked collaboratively with the study team to develop a training curriculum to
      implement in their community. Community-based surveys, interviews, and focus
      group discussions were used to assess acceptability, accessibility, and
      availability of oral rehydration therapy and zinc supplementation. Results: Use
      of ORT increased from 63% to 95% among community members following training by
      local health promoters. Satisfaction with the service offered by health promoters
      increased from 63% to 90% amongst community members trained by the study
      promoters. However, knowledge and use of zinc supplementation remained low, which
      was attributable to unavailability of zinc in the study community. Conclusions:
      Use of trained community health promoters is an effective way to translate WHO
      guidelines to local contexts and overcome sociocultural barriers to care.
      However, the health system's structure must support availability of essential
      medicines in order to effectively implement those guidelines.

PMID- 28444009
TI  - [Antituberculosis-drug resistance in the border of Brazil with Paraguay and
      Bolivia].
AB  - Objective: To estimate the rate of drug resistance among pulmonary tuberculosis
      (PTB) cases in the state of Mato Grosso do Sul, Brazil, and specifically in the
      border areas with Paraguay and Bolivia, as well as to identify associated risk
      factors. Method: The present cross-sectional, epidemiological study focused on
      PTB cases recorded between January 2007 and December 2010 in the State Reportable
      Disease Information System with results of susceptibility tests to rifampicin,
      isoniazid, ethambutol, and streptomycin. Dependent variables were development of
      resistance to a single drug or any combination of drugs. Independent variables
      were being a new or treated case, living in border areas, presence/absence of
      diabetes, and history of alcoholism. Results: There were 789 TBP cases with
      susceptibility testing. The following characteristics were associated with
      resistance: treated case (P = 0.0001), border region (P = 0.0142), alcoholism (P
      = 0.0451), and diabetes (P = 0.0708). The rates of combined, primary, and
      acquired resistance for the state were 16.3%, 10.6%, and 39.0%, vs. 22.3%, 19.2%,
      and 37.5% for the border region. The rates of combined, primary, and acquired
      multidrug resistance for the state were 1.8%, 0.6%, and 6.3%, vs. 3.1%, 1.2%, and
      12.5% for the border region. Conclusions: In the border region, the state should
      investigate drug resistance in all patients with respiratory symptoms, determine
      the pattern of resistance in confirmed cases, adopt directly observed treatment
      for cases of PTB, and develop health actions together with neighboring countries.
      Across the state, the levels of acquired resistance should be monitored, with
      investigation of resistance in all treated cases and implementation of directly
      observed treatment especially among patients with diabetes or alcoholism.

PMID- 28444011
TI  - Prototype to measure bracket debonding force in vivo.
AB  - INTRODUCTION: Material biodegradation that occurs in the mouth may interfere in
      the bonding strength between the bracket and the enamel, causing lower bond
      strength values in vivo, in comparison with in vitro studies. OBJECTIVE: To
      develop a prototype to measure bracket debonding force in vivo and to evaluate,
      in vitro, the bond strength obtained with the prototype. METHODS: A original
      plier (3M Unitek) was modified by adding one strain gauge directly connected to
      its claw. An electronic circuit performed the reading of the strain gauge, and
      the software installed in a computer recorded the values of the bracket debonding
      force, in kgf. Orthodontic brackets were bonded to the facial surface of 30
      bovine incisors with adhesive materials. In Group 1 (n = 15), debonding was
      carried out with the prototype, while tensile bond strength testing was performed
      in Group 2 (n = 15). A universal testing machine was used for the second group.
      The adhesive remnant index (ARI) was recorded. RESULTS: According to Student's t
      test (alpha = 0.05), Group 1 (2.96 MPa) and Group 2 (3.08 MPa) were not
      significantly different. ARI score of 3 was predominant in the two groups.
      CONCLUSION: The prototype proved to be reliable for obtaining in vivo bond
      strength values for orthodontic brackets.

PMID- 28444010
TI  - Three dimensional evaluation of alveolar bone changes in response to different
      rapid palatal expansion activation rates.
AB  - INTRODUCTION: The aim of this multi-center retrospective study was to quantify
      the changes in alveolar bone height and thickness after using two different rapid
      palatal expansion (RPE) activation protocols, and to determine whether a more
      rapid rate of expansion is likely to cause more adverse effects, such as alveolar
      tipping, dental tipping, fenestration and dehiscence of anchorage teeth. METHODS:
      The sample consisted of pre- and post-expansion records from 40 subjects (age 8
      15 years) who underwent RPE using a 4-banded Hyrax appliance as part of their
      orthodontic treatment to correct posterior buccal crossbites. Subjects were
      divided into two groups according to their RPE activation rates (0.5 mm/day and
      0.8 mm/day; n = 20 each group). Three-dimensional images for all included
      subjects were evaluated using Dolphin Imaging Software 11.7 Premium. Maxillary
      base width, buccal and palatal cortical bone thickness, alveolar bone height, and
      root angulation and length were measured. Significance of the changes in the
      measurements was evaluated using Wilcoxon signed-rank test and comparisons
      between groups were done using ANOVA. Significance was defined at p <= 0.05.
      RESULTS: RPE activation rates of 0.5 mm per day (Group 1) and 0.8 mm per day
      (Group 2) caused significant increase in arch width following treatment; however,
      Group 2 showed greater increases compared to Group 1 (p < 0.01). Buccal alveolar
      height and width decreased significantly in both groups. Both treatment protocols
      resulted in significant increases in buccal-lingual angulation of teeth; however,
      Group 2 showed greater increases compared to Group 1 (p < 0.01). CONCLUSION: Both
      activation rates are associated with significant increase in intra-arch widths.
      However, 0.8 mm/day resulted in greater increases. The 0.8 mm/day activation rate
      also resulted in more increased dental tipping and decreased buccal alveolar bone
      thickness over 0.5 mm/day.

PMID- 28444012
TI  - Are there differences between comparison methods used to evaluate the accuracy
      and reliability of digital models?
AB  - OBJECTIVES: The accuracy and reliability of plaster models and digital models
      acquired with two different surface laser scanners were tested by means of three
      methods: measurement with calipers, digital measurement with proper software and
      superimposition of the digital models. METHODS: Thirty plaster models with
      permanent dentition that met the inclusion criteria were selected and scanned
      with two laser scanners (R700 and Xcad). Three examiners measured distances on
      plaster models with a digital caliper and on digital models using Ortho Analyzer
      software. The digital models were also compared by means of superimposition of
      the models using the Geomagic Qualify software. The intra and inter-examiner
      reliability of the measurements were evaluated using the ICC. Paired t test was
      used to test the accuracy of the measurements on digital and plaster models.
      RESULTS: The measurements on plaster and digital models acquired by two different
      scanners showed high values for the ICC. Although statistically significant
      differences between the measurements on plaster and digital models have been
      found, these discrepancies were not considered clinically relevant. The
      superimposition method with Geomagic Qualify software showed that the two digital
      models were not significantly different. CONCLUSIONS: Digital models created from
      scanned plaster models using the R700 or Xcad scanners were clinically accurate
      according to the two methods of comparison used.

PMID- 28444013
TI  - Third molars and premolars extraction in conventional orthodontics and in
      treatments based on maxillary bone remodeling with temporary anchorage:
      indications and care.
AB  - A bone is an anatomic structure in constant remodeling, with different, mutant
      and wonderfully inconstant designs. With every new and immediate functional
      demand, there are changes in cortical thickness, trabecular bone density and also
      in direction and size of trabeculae. Bones' non-stopping search is for adjusting
      to the functions induced by forces and movements required by a certain life
      style. Conventional orthodontic planning or with temporary anchorage based on
      bone remodeling takes into consideration the spaces that are - or may be -
      occupied by the teeth, in the formation of a functional and esthetic dental arch
      for the patient. In case it is necessary to extract a tooth and the options are
      the third molars, partially or totally unerupted, and teeth that belong to other
      dental groups, obviousness recommends - due to mouth anatomy and physiology, as
      well as pathologic reasons - extracting the third molars, due to of the several
      reasons described in the present study.

PMID- 28444014
TI  - Photoelastic analysis of stress generated by Connecticut Intrusion Arch (CIA).
AB  - OBJECTIVE: The present in vitro study evaluated, by means of the photoelastic
      technique, the effects generated by the Connecticut Intrusion Arch (CIA), with a
      90o bend on the distal surface of molar tubes and using the 4 x 2 appliance on
      the anterior and posterior regions of the upper dental arch. METHODS: Five models
      were manufactured, in which two different clinical situations were correlated: 1)
      use of intrusion arch not cinched back and transpalatal bar for anchorage (Group
      1); 2) use of intrusion arch cinched back and transpalatal bar for anchorage
      (Group 2). Stress generated in the apical and middle regions of tooth roots of
      maxillary anterior teeth and maxillary first molars was evaluated. RESULTS:
      Taking a reference value of 1.0 MPa = 100%, qualitative descriptive analysis was
      performed, which showed uniformity between stress values in the apical region of
      anterior teeth of both groups (G1 and G2). In the posterior region, for models
      with the arch cinched back (G2), stress remained within 100%. As for G1 models
      (with the arch not cinched back), variations in the mesial surface of first
      molars were observed, with an increase of 20% in the generated stress. The apical
      region did not undergo any changes, while in the distal region of molars there
      was a decrease of 20% in stress. CONCLUSION: Laboratory results revealed
      differences in stress between Groups 1 and 2 in the molar region, thereby
      indicating that there was a tendency towards mesial root tipping of first molars
      when the distal end of the CIA was not cinched back.

PMID- 28444015
TI  - A new QUALIS for the Dental Press Journal of Orthodontics.

PMID- 28444016
TI  - Frictionless segmented mechanics for controlled space closure.
AB  - Extraction spaces may be needed to achieve specific orthodontic goals of
      positioning the dentition in harmony with the craniofacial complex. However, the
      fundamental reality that determines the occlusion final position is the control
      exerted by the orthodontist while closing the extraction spaces. A specific
      treatment objective may require the posterior teeth to remain in a constant
      position anteroposteriorly as well as vertically, while the anterior teeth occupy
      the entire extraction site. Another treatment objective may require the opposite,
      or any number of intentional alternatives of extraction site closure. The present
      case report describes a simple controlled segmented mechanic system that
      permitted definable and predictable force systems to be applied and allowed to
      predict the treatment outcome with confidence. This case was presented to the
      Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) in partial
      fulfillment of the requirements for Diplomate certification.

PMID- 28444017
TI  - An interview with Jimmy C. Boley.

PMID- 28444018
TI  - Effect of nanotechnology in self-etch bonding systems on the shear bond strength
      of stainless steel orthodontic brackets.
AB  - OBJECTIVE: To evaluate the effect of silica dioxide (SiO2) nanofillers in
      different bonding systems on shear bond strength (SBS) and mode of failure of
      orthodontic brackets at two experimental times. METHODS: Ninety-six intact
      premolars were divided into four groups: A) Conventional acid-etch and primer
      Transbond XT; B) Transbond Plus self-etch primer; and two self-etch bonding
      systems reinforced with silica dioxide nanofiller at different concentrations: C)
      Futurabond DC at 1%; D) Optibond All-in-One at 7%. Each group was allocated into
      two subgroups (n = 12) according to experimental time (12 and 24 hours). SBS test
      was performed using a universal testing machine. ARI scores were determined under
      a stereomicroscope. Scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM) were used to determine the size and distribution of nanofillers.
      One-way ANOVA was used to compare SBS followed by the post-hoc Tukey test. The
      chi-square test was used to evaluate ARI scores. RESULTS: Mean SBS of Futurabond
      DC and Optibond All-in-One were significantly lower than conventional system, and
      there were no significant differences between means SBS obtained with all self
      etch bonding systems used in the study. Lower ARI scores were found for
      Futurabond DC and Optibond All-in-One. There was no significant difference of SBS
      and ARI obtained at either time points for all bonding systems. Relative
      homogeneous distribution of the fillers was observed with the bonding systems.
      CONCLUSION: Two nanofilled systems revealed the lowest bond strengths, but still
      clinically acceptable and less adhesive was left on enamel. It is advisable not
      to load the brackets immediately to the maximum.

PMID- 28444019
TI  - Non-surgical treatment of transverse deficiency in adults using Microimplant
      assisted Rapid Palatal Expansion (MARPE).
AB  - INTRODUCTION: Maxillary transverse deficiency is a highly prevalent malocclusion
      present in all age groups, from primary to permanent dentition. If not treated on
      time, it can aggravate and evolve to a more complex malocclusion, hindering
      facial growth and development. Aside from the occlusal consequences, the
      deficiency can bring about serious respiratory problems as well, due to the
      consequent nasal constriction usually associated. In growing patients, this
      condition can be easily handled with a conventional rapid palatal expansion.
      However, mature patients are frequently subjected to a more invasive procedure,
      the surgically-assisted rapid palatal expansion (SARPE). More recently,
      researches have demonstrated that it is possible to expand the maxilla in grown
      patients without performing osteotomies, but using microimplants anchorage
      instead. This novel technique is called microimplant-assisted rapid palatal
      expansion (MARPE). OBJECTIVE: The aim of the present article was to demonstrate
      and discuss a MARPE technique developed by Dr. Won Moon and colleagues at
      University of California - Los Angeles (UCLA). METHODS: All laboratory and
      clinical steps needed for its correct execution are thoroughly described. For
      better comprehension, a mature patient case is reported, detailing all the
      treatment progress and results obtained. CONCLUSION: It was concluded that the
      demonstrated technique could be an interesting alternative to SARPE in the
      majority of non-growing patients with maxillary transverse deficiency. The
      present patient showed important occlusal and respiratory benefits following the
      procedure, without requiring any surgical intervention.

PMID- 28444020
TI  - Deformation of nickel-titanium closed coil springs: an in vitro study.
AB  - OBJECTIVE: The aim of this paper was to determine the amount of deformation in
      four commercial brands of nickel-titanium closed springs. METHODS: A total of 130
      springs were divided into 13 subgroups, according to their features and
      manufacturers (Morelli, Orthometric, Ormco and GAC) and activated from 100% to
      1000% of the effective length of the nickel-titanium portion present at the
      spring, at 37  degrees C. Deactivation data were plotted and deformation was
      found graphically. The values were compared by analysis of variance and Tukey's
      post-hoc test. RESULTS: Springs manufactured by Morelli had the same amount of
      deformation when they were activated up to 700% of Y activation; springs by
      Orthometric had the same amount of deformation up to 600-700% of Y; springs by
      Ormco had the same amount of deformation up to 700-800% of Y; and finally, the
      majority of springs by GAC had similar deformation up to 800%-1000% of
      activation. All springs tested could be activated up to 700% without rupture.
      CONCLUSIONS: Most subgroups were similarly deformed up to 700% of activation,
      without rupture of springs. Subgroups 4B, 4C, 4D and 4E showed the same amount of
      deformation up to 1000% of activation without any rupture at all.

PMID- 28444021
TI  - Evaluation of facial attractiveness in black people according to the subjective
      facial analysis criteria.
AB  - OBJECTIVE: The objective of this study was to evaluate the facial attractiveness
      in 30 black individuals, according to the Subjective Facial Analysis criteria.
      METHODS: Frontal and profile view photographs of 30 black individuals were
      evaluated for facial attractiveness and classified as esthetically unpleasant,
      acceptable, or pleasant by 50 evaluators: the 30 individuals from the sample, 10
      orthodontists, and 10 laymen. Besides assessing the facial attractiveness, the
      evaluators had to identify the structures responsible for the classification as
      unpleasant and pleasant. Intraexaminer agreement was assessed by using Spearman's
      correlation, correlation within each category using Kendall concordance
      coefficient, and correlation between the 3 categories using chi-square test and
      proportions. RESULTS: Most of the frontal (53. 5%) and profile view (54. 9%)
      photographs were classified as esthetically acceptable. The structures most
      identified as esthetically unpleasant were the mouth, lips, and face, in the
      frontal view; and nose and chin in the profile view. The structures most
      identified as esthetically pleasant were harmony, face, and mouth, in the frontal
      view; and harmony and nose in the profile view. The ratings by the examiners in
      the sample and laymen groups showed statistically significant correlation in both
      views. The orthodontists agreed with the laymen on the evaluation of the frontal
      view and disagreed on profile view, especially regarding whether the images were
      esthetically unpleasant or acceptable. CONCLUSIONS: Based on these results, the
      evaluation of facial attractiveness according to the Subjective Facial Analysis
      criteria proved to be applicable and to have a subjective influence; therefore,
      it is suggested that the patient's opinion regarding the facial esthetics should
      be considered in orthodontic treatmentplanning.

PMID- 28444022
TI  - On bringing people together and other matters. Interview with Professor Trevor
      Bailey.

PMID- 28444023
TI  - [Conicity index as a predictor of changes in the lipid profile of adolescents in
      a city in Northeast Brazil].
AB  - The objective was to evaluate the conicity index (C Index) as a predictor of
      changes in the lipid profile of adolescents and to establish its cutoff points.
      This was a cross-sectional study in 774 adolescents of both sexes (55% girls), 10
      to 14 years of age. C Index was calculated according to the formula proposed by
      Valdez, considering body mass, height, and waist circumference (WC). Changes in
      the adolescents' lipid profile were defined according to one of the following
      conditions: elevated levels of total cholesterol, low-density lipoprotein (LDL),
      and triglycerides and low levels of high-density lipoprotein (HDL). The
      predictive power of the conicity index for altered lipid profile and its cutoff
      points were determined by Receiver Operating Characteristic (ROC) curves. The C
      Index was a good predictor of lipid alterations in adolescents, emphasizing
      triglycerides in boys 10 to 11 years of age (ROC = 0.67; 95%CI: 0.50-0.85) and 12
      to 14 (ROC = 0.69; 95%CI: 0.59-0.80), and in girls 10 to 11 years (ROC = 0.65;
      95%CI: 0.50-0.79); and LDL in girls 10 to 11 years (ROC = 0.70; 95%CI: 0.59-0.80)
      and boys (ROC = 0.65; 95%CI: 0.55-0.75) and girls (ROC = 0.62; 95%CI: 0.50-0.75)
      12 to 14 years. The cutoff points for the C Index varied from 1.12 to 1.16
      between boys and girls. The C Index can be used to predict lipid alterations, and
      its cutoff points can be used to screen adolescents for risk of alterations in
      lipid profile.

PMID- 28444024
TI  - Public security in a violent country.

PMID- 28444025
TI  - Risk of misinterpretation of trends in hospital admissions for primary care
      sensitive conditions in local contexts: Itaborai, Rio de Janeiro State, Brazil,
      2006-2011.
AB  - The study's objectives were to describe hospital admissions for primary care
      sensitive conditions (PCSCs) among residents of Itaborai, a municipality in Rio
      de Janeiro State, Brazil, with a high rate of such admissions, to identify
      associated factors, and to explore the impact from closing a hospital. The
      ultimate aim was to contribute to the debate on the indicator's indiscriminate
      use for inferences on the expansion and quality of primary care. The study was
      based on data from the Hospital Information System of the Brazilian Unified
      National Health System. Associations between admissions for PCSCs and demographic
      and hospital-related variables were analyzed with the chi2 test. Logistic
      regression models verified the year-by-year behavior of admissions for PCSCs. The
      most frequent admissions were for heart failure, asthma, gastroenteritis, chronic
      obstructive pulmonary disease, and diabetes mellitus. The odds of hospital
      admissions were higher in males, brown individuals, at age extremes, and in
      private and charity hospitals. The trend in the admissions rates for PCSCs over
      the years was influenced by the closing of a hospital, suggesting caution in
      attributing changes in admissions rates to quality improvement in primary care.

PMID- 28444026
TI  - Use of pharmacy records to measure treatment adherence: a critical review of the
      literature.
AB  - The current frame of reference on adherence to pharmacotherapy includes a set of
      behaviors experienced by the user, with observation of the detailed and
      continuous history of the use of each dose of the medication. Indicators based on
      pharmacy records have been used to measure adherence. The current review aimed to
      identify and describe indicators based on pharmacy records and to discuss their
      adequacy and limitations for measuring adherence. An exploratory literature
      review was conducted in three databases using the terms "adherence", "pharmacy
      records/administrative data", and "measure" to compose the descriptors for the
      selection of 81 articles and the elaboration of a chart with the denomination,
      sources, methods for calculation, description, and interpretation of the
      operational and referential meaning of 14 indicators. Given the most recent
      taxonomy for adherence proposed in the literature, we concluded that the
      indicators can be useful for identifying patients with medication-seeking
      behavior-related problems and analysis of persistence. The distance between
      supply-related events and difficulties in treatment follow-up can influence an
      analysis based exclusively on the use of these indicators.

PMID- 28444028
TI  - [Late maternal mortality: comparison of maternal mortality committees in Brazil].
AB  - This population-based study included all the late maternal deaths from the case
      series of the Maternal Mortality Committees in the city of Sao Paulo and the
      state of Parana, Brazil. The study compared 134 deaths identified by the Sao
      Paulo committee and 124 from the Parana committee in 2004-2013, aimed at
      demonstrating the magnitude and causes of late maternal mortality. Late maternal
      deaths accounted for 13.4% of all maternal deaths in the case series of the Sao
      Paulo committee and 12.1% in the cases series of the Parana committee. Direct
      obstetric causes accounted for 32.1% of the late maternal deaths in Sao Paulo and
      42.1% in Parana, with postpartum cardiomyopathy as the principal cause in both
      case series. Death occurred between 43 and 69 days postpartum in 44% of the cases
      in Sao Paulo and 39.5% in Parana. The correction factor for late maternal death
      was 3.3 in Sao Paulo and 4.3 in Parana. Late maternal death had a relevant impact
      on overall maternal mortality, and postpartum cardiomyopathy was the principal
      cause of late direct obstetric death.

PMID- 28444027
TI  - Precarious employment in Chile: psychometric properties of the Chilean version of
      Employment Precariousness Scale in private sector workers.
AB  - The purpose of this study is to perform a psychometric analysis (acceptability,
      reliability and factor structure) of the Chilean version of the new Employment
      Precariousness Scale (EPRES). The data is drawn from a sample of 4,248 private
      salaried workers with a formal contract from the first Chilean Employment
      Conditions, Work, Health and Quality of Life (ENETS) survey, applied to a
      nationally representative sample of the Chilean workforce in 2010. Item and scale
      level statistics were performed to assess scaling properties, acceptability and
      reliability. The six-dimensional factor structure was examined with confirmatory
      factor analysis. The scale exhibited high acceptability (roughly 80%) and
      reliability (Cronbach's alpha 0.83) and the factor structure was confirmed. One
      subscale (rights) demonstrated poorer metric properties without compromising the
      overall scale. The Chilean version of the Employment Precariousness Scale (EPRES
      Ch) demonstrated good metric properties, pointing to its suitability for use in
      epidemiologic and public health research.

PMID- 28444029
TI  - [Risk of exposure to heatstroke in sugarcane workers in Sao Paulo State, Brazil].
AB  - Environmental heat is an aggravating factor for sugarcane workers, and manual
      cane cutting is one of the heavy work activities that favor the generation of
      metabolic heat. This can combine with other precarious working conditions to
      produce heatstroke, potentially leading to serious complications and even death.
      The study aimed to quantify the risk of overheating in sugarcane cutters in Sao
      Paulo, Brazil. Drawing on a specific methodology, the study used four years of
      data to estimate the Globe Thermometer Wet Bulb Index based on light, moderate,
      and heavy activities. The results showed that the legal limit was exceeded for
      continuous activity in periods from 1 to 8 hours, which requires control measures
      in order to continue working. The principal observation was the risk of
      heatstroke in the three types of activity: light, moderate, and heavy. The limits
      were exceeded throughout the work shift on 7% of the days for heavy activity and
      on 3% of the days for moderate activity. In addition, the areas with the highest
      risk of heatstroke coincide with predominant cane-growing.

PMID- 28444031
TI  - Health policies and federative gaps in Brazil: an analysis of regional capacity
      of services delivery.
AB  - This paper analyzes Brazilian health regions according to their service delivery
      capacity from the debate on the crisis of cooperative federalism in the SUS that
      resulted from decentralizing process established in the 1988 Constitution.
      Service delivery capacity tracer indicators were selected by regions and
      statistical analyses evidenced greater regional capacity in hospital care and
      large asymmetries with regard to the availability of physicians, high complexity
      equipment and private insurance coverage. In conclusion,we argue that further
      solutions are required to strengthen governmental capacity to reduce regional
      inequalities throughincreased central coordination.

PMID- 28444030
TI  - Regional inequalities, cooperative federalism and challenges facing the SUS.

PMID- 28444032
TI  - Thoughts on the development of active regional public health systems.
AB  - Decentralization and regionalization are strategic themes for reforms in the
      health system. This paper analyzes the complex process of health regionalization
      being developed in Brazil. This paper identifies that the normative framework
      from the Brazilian National Health System, SUS has made advances with respect to
      its institutionalization and overcoming the initial centrality involved in
      municipalization. This has strengthened the development of regionalization and
      the intergovernmental agreement on health but the evidence points to the need to
      promote a revision. Based on document analysis, literature review and the views
      given by the authors involved in management in SUS as well as generating
      radically different views, the challenges for the construction of a
      regionalization that is active, is debated. We also discuss: its relations with
      planning and the dimensioning of service networks, the production of active care
      networks and shared management spaces, the inter-federative agreements and
      regional regulations, the capacity to coordinate regional systems and financing
      and the impact of the political dimension and electoral cycles. Regionalization
      (and SUS itself) is an open book, therefore ways and possibilities on how to
      maintain an active form of regionalization can be recommended.

PMID- 28444033
TI  - Regional health inequalities: changes observed in Brazil from 2000-2016.
AB  - Advances in reducing poverty and inequalities in the 2000s had a paradoxical
      effect in Brazil. This article examines how socioeconomic transformations, and
      the complexity of health services, are expressed in the regions established for
      planning purposes and the inter-governmental management of the Brazilian Unified
      Health System. An effort was made to identify and explain differences in the
      compositions of the 438 existing health regions and their spatial distribution by
      comparing situations observed in 2016 with those in 2000. Factor analysis and
      grouping techniques were used to construct a typology in the two years of the
      series, which was based on a diverse set of secondary data sources. It was found
      that there was an evolution in terms of income levels and service provision
      within the health regions, with a significant improvement in the socioeconomic
      conditions of the population. These results suggest that there was a positive
      impact from the combination of strategies related to social, economic and
      regional policies for the promotion of development, which generated more
      widespread well-being within the affected areas. However, limitations remain
      regarding the policies implemented for the universalization of the health system.

PMID- 28444034
TI  - Brazilian healthcare in the context of austerity: private sector dominant,
      government sector failing.
AB  - This paper presents the arguments in favor of government intervention in
      financing and regulation of health in Brazil. It describes the organizational
      arrangement of the Brazilian health system, for the purpose of reflection on the
      austerity agenda proposed for the country. Based on the literature in health
      economics, it discusses the hypothesis that the health sector in Brazil functions
      under the dominance of the private sector. The categories employed for analysis
      are those of the national health spending figures. An international comparison of
      indicators of health expenses shows that Brazilian public spending is a low
      proportion of total spending on Brazilian health. Expenditure on individuals'
      health by out-of-pocket payments is high, and this works against equitability.
      The private health services sector plays a crucial role in provision, and
      financing. Contrary to the belief put forward by the austerity agenda, public
      expenditure cannot be constrained because the government has failed in adequate
      provision of services to the poor. This paper argues that, since the Constitution
      did not veto activity by the private sector segment of the market, those
      interests that have the greatest capacity to vocalize have been successful in
      imposing their preferences in the configuration of the sector.

PMID- 28444035
TI  - Regional Governance in Brazil's Unified Health System: a conceptual essay.
AB  - This article is a conceptual essay aimed at supporting analyses of the
      regionalization processes implemented in Brazil's Unified Health System, from the
      perspective of regional governance. The authors conducted a literature review in
      the social sciences, public administration, and critical geography, focusing on
      the concepts of governance, territorial governance, and regional governance in
      the debate on development. In dialogue with these contributions to the analysis
      of recent regulation and implementation of health sector regionalization in
      Brazil, with special reference to use of the Organizational Contract for Public
      Action (COAP) in the country's health regions, the article concludes that the
      research on governance as a modern approach to linking public policies highlights
      the timeliness of developing methodologies and critical reflection on the
      relevant national processes in Brazil for future health sector proposals, thereby
      pointing to a new stage in the improvement of the Unified Health System.

PMID- 28444036
TI  - Theoretical reflections on governance in health regions.
AB  - This article analyzes governance in health regions, through the contributions of
      two studies: one on a governance model and the other on duties in the management
      of public policies networks. The former conducted a meta-analysis of 137 case
      studies in the literature on collaborative governance aimed at preparing an
      explanatory and analytical model. Authors identified critical variables that will
      influence the results: a previous history of conflict or cooperation, incentives
      for participation, power imbalances, leadership and institutional design. They
      also identified key factors: face-to-face dialogue, trust building and
      development of commitment and shared vision. The latter study examined networks
      of public policies in the analytic tradition and the perspective of governance,
      incorporating concepts from the field of political science, economics and
      interorganizational relations, in order to support the management of public
      policies networks. The study identified network management as equivalent to a
      strategic game involving functions: network activation, framework of relations,
      intermediation, facilitation and consensus building and mediation and
      arbitration. The combination of the two reflections provides a conceptual
      reference for better understanding of governance in health regions.

PMID- 28444037
TI  - Political Obstacles to Regionalization of the SUS: perceptions of Municipal
      Health Secretaries with seat in the Bipartite Interagency Commissions.
AB  - This paper aims to identify and analyze the political obstacles to the
      implementation of Organizational Contract of Public Action (COAP) based on the
      perceptions of municipal health secretaries of Bipartite Interagency Commissions
      (CIB). For this purpose, we interviewed 195 secretaries (92% of the total) from
      October 2015 to August 2016. Based on the approach of policy analysis, the main
      hurdles identified were, in short, a traditional obstacle (lack of resources),
      one that has been gaining strength in recent years (judicialization of politics)
      and another, perhaps unheard of: the party-political system and the State
      Executive Branch are the great absentees in the coalitions in support of SUS
      regionalization policies. We can conclude that such obstacles indicate an
      extremely negative setting for the implementation of the COAP and other SUS
      regionalization policies. Thus, it is incumbent upon those involved to reflect,
      negotiate and build consensus on improving the health of the population and
      overcome such obstacles if, of course, they embrace the authors' concept that
      regionalization is fundamental for the SUS.

PMID- 28444038
TI  - Difficulties in accessing services that are of medium complexity in small
      municipalities: a case study.
AB  - The study aimed to describe the specialized health services and to identify areas
      of greater difficulty of access to specialized consultations offered by SUS in
      small cities in the 18th Regional Health Area of Parana State, Brazil, using case
      study methodology. The data were collected between January and April 2015.
      Managers, management teams and the board of directors of the CIS (Consorcio
      Intermunicipal de Saude) were interviewed. The 21 studied specialist areas were
      rated like Sufficient Quota, Insufficient Quota, Inexistent Supply, and
      Assistance Gap. The services with more difficulty of access were Vascular
      Surgery, Proctology, Geriatrics, Endocrinology, and Neurology, considered
      Inexistent Supply/Assistance Gap, and Orthopedics, Neuro-pediatrics, Urology,
      Rheumatology, Ophthalmology, and Otorhinolaryngology, were considered
      Insufficient Share. Contribute to the magnitude of the problem: lack of
      specialist doctors, private sector dependence and de decrease of the Federal and
      State Governments in financing the Health Sistem. Therefore, the gap in
      specialized healthcare is complex and difficult to solve in the short-terms,
      proving that this services have become a "bottleneck" in the SUS.

PMID- 28444039
TI  - The health regionalization process from the perspective of the transation cost
      theory.
AB  - This study analyzes the incidence of transaction costs in the regionalization
      process of health policies in the Brazilian federal system. In this work,
      regionalized health actions contracted and agreed between federal agencies have
      assumed a transactional nature. A conceptual theoretical essay of reflective
      nature was prepared with the purpose of questioning and proposing new approaches
      to improve the health regionalization process. The main considerations suggest
      that institutional management tools proposed by the standards and regulations of
      the Unified Health System have a low potential to reduce transaction costs,
      especially due to hardships in reconciling common goals among the entities,
      environment surrounded by uncertainty, asymmetries and incomplete information,
      bounded rationality and conflict of interest. However, regionalization can reduce
      the incidence of social and/or operational costs, through improved access to
      health and the construction of more efficient governance models.

PMID- 28444040
TI  - The prominent role of Councils of Municipal Health Secretariats in the regional
      governance process.
AB  - This study aims to analyze the perception of managers of the Councils of
      Municipal Health Secretariats (COSEMS) and their contributions to the health
      regionalization process. We conducted thorough interviews with presidents of
      COSEMS of the states of Mato Grosso do Sul, Parana, Ceara, Tocantins and Minas
      Gerais. Data were analyzed with Iramuteq software, which generated a dendrogram
      with three themes: The first thematic axis: the prominent role of COSEMS in the
      regional governance process, which includes class 1 - COSEMS' leadership in the
      process of regionalization, and class 3 - The strategic experience of the
      regional agreement process. The second thematic axis includes the challenges to
      the provision of health care in the regions, consisting of class 2, which shows
      how to meet community needs, and class 4, which shows the local support carried
      out by COSEMS' teams. The third thematic axis consists of class 5, which
      describes the operational aspects of the provision of health care in the region.
      COSEMS play an important role in the regionalization process, especially because
      they have an organic performance and leadership. Its organic performance in these
      areas has ensured its legitimacy and leadership. It is a daily construction that
      ensures the advancement of collaborative governance in health regions.

PMID- 28444041
TI  - Primary health care and the coordination of care in health regions: managers' and
      users' perspective.
AB  - This paper aims to analyze the healthcare coordination by Primary Health Care
      (PHC), with the backdrop of building a Health Care Network (RAS) in a region in
      the state of Sao Paulo, Brazil. We conducted a case study with qualitative and
      quantitative approaches, proceeding to the triangulation of data between the
      perception of managers and experience of users. We drew analysis realms and
      variables from the three pillars of healthcare coordination - informational,
      clinical and administrative/organizational. Stroke was the tracer event chosen
      and therapeutic itineraries were conducted with users and questionnaires applied
      to the managers. The central feature of the construction of the Health Care
      Network in the studied area is the prominence of a philanthropic organization.
      The results suggest fragility of PHC in healthcare coordination in all analyzed
      realms. Furthermore, we identified a public-private mix, in addition to services
      contracted from the Unified Health System (SUS), with out-of-pocket payments for
      specialist consultation, tests and rehabilitation. Much in the same way that
      there is no RAS without a robust PHC capable of coordinating care, PHC is unable
      to play its role without a solid regional arrangement and a virtuous articulation
      between the three federative levels.

PMID- 28444042
TI  - Regionalization in the SUS: implementation process, challenges and perspectives
      in the critical view of system managers.
AB  - This article examines the regionalization process in the Brazilian Health System,
      identifying frameworks and challenges of this process from critical dialogue on
      the subject, contextualized by the experience of the management system and in the
      light of an established theoretical debate in the last decade. We used the
      thematic content analysis of legal and documentary surveys of the regionalization
      process in SUS, collated by elements of the historical and political context in
      the period. As evidence, it appears that the regionalization process has been
      incremental decentralization/deconcentration of management and health actions and
      services. There are important challenges, particularly in relation to ensuring
      access and system governance structure, which contributes to critical thinking
      and construction of new perspectives by those who lead their implementation.

PMID- 28444043
TI  - Challenges for ensuring availability and accessibility toin health care services
      under Brazil's Unified Health System (SUS).
AB  - Shortages and imbalances in the distribution of the health workforce, are social
      and political problems that, along with the socio-economic inequality, reduce the
      access of the population to the health services. This study aims to understand
      the challenges of SUS policy-makers and managers to ensure the availability and
      geographical accessibility to health service providers. The analysis was guided
      by a framework of the health labour market and health policy interventions. Two
      main problems have been identified: shortage of doctors and maldistribution of
      professionals between levels of health care and between geographical areas. This
      review focused on eight interventions in the last 30 years, whose mainly aim was
      to correct the maldistribution of physicians in the SUS such as Rondon Project,
      Interiorization of Health Work Program, Medical Specialists Training Program, PHC
      Program and More Doctors Program. The discussion focuses on the factors that
      influence the outcome of these interventions.

PMID- 28444044
TI  - Comments on "The organization of pharmaceutical services by 'health region' in
      Brazil's Unified Health System".
AB  - This study aimed to describe and characterize the pharmaceutical services
      provided in Brazil's Unified Health System (SUS) from the point of view of the
      healthcare networks that are organized by region in the QualiSUS-Rede Project.
      This was a cross-sectional study, with data collected from December 2013 to July
      2015, in public health establishments that carried out delivery or warehousing of
      medications (n = 4,938), in 465 municipalites, and the Federal District, in
      43'Health Regions'. The results show the existence of at least one management
      service supporting the health network, and warehousing of medications in all the
      regions (> 90%). It also showed the availability of at least one healthcare
      service, in healthcare locations, by pharmaceutical professionals is irregular
      between the Regions, being highest in the Southeastern Region (74.3%), and lowest
      in the Northeastern Region (43.3%). The results underpine the need for effective
      structuring of pharmaceutical assistance in the SUS networks, overcoming the
      current restrictive vision of its activities, which gives value almost
      exclusively to the logistical component of support to the network, to the
      detriment of the clinical component. It is also important to expand, and improve
      the quality of, the population's access to medical drugs, and improve the quality
      of the healthcare offered to users of the system.

PMID- 28444045
TI  - Coap and SUS Regionalization: the various implementation patterns in the
      Brazilian states.
AB  - This paper analyzes the implementation process of the Public Action
      Organizational Contract (Coap) and its impacts on state agendas of SUS
      regionalization, comparing the different institutional reactions of the states to
      the strategy proposed by Decree 7.508/11. The comparison of developing dynamics
      of state agendas took as reference a normative baseline structured in eight
      strategic political-institutional moments in the implementation of the Coap in
      accordance with the logic defined in Decree 7.508/11. We collected data through a
      questionnaire containing 35 questions (1 open, 25 closed and 9 mixed) and
      extensive documentary research in 2013 and 2014 in all states, except for the
      Federal District. Results showed that state agendas were distributed around three
      differentiated developing patterns: six states maintained greater distance from
      the national agenda established by Decree 7.508/11, engaging in a very fragmented
      way; 12 states engaged in the Coap agenda, selectively focusing on specific
      moments or stages, strengthening the process they have been developing; and 10
      states maintained greater performance regularity during the eight moments of the
      Coap implementation cycle.

PMID- 28444046
TI  - Health care networks implementation and regional governance challenges in the
      Legal Amazon Region: an analysis of the QualiSUS-Rede Project.
AB  - This paper aims to analyze the potential, limits and challenges of regional
      governance in the implementation process of health care networks in three
      Brazilian regions: Alto Solimoes (Amazonas), Belem (Para) and an interstate
      region comprising Tocantins, Para and Maranhao states (Topama). The study is
      based on the evaluation study on the implementation of the Quality Health Care
      Network Development and Improvement Project (QualiSUS-Rede). This is a
      qualitative multiple case study with the analysis of official documents and use
      of semi-structured interviews with key stakeholders conducted from July to
      December 2014. Governance review encompassed three components: stakeholders
      involved, especially local steering groups and their regional coordination
      capacity; strategies used for strengthening regional governance, anchored on the
      intervention's modeling; and implementation of local health care networks.
      Results point that the regional managing commissions were the main governance
      strategy and that the QualiSUS-Rede Project strengthened regional governance and
      integration differently in every case, depending on stakeholders' administration
      and consensus capacity on regional and political priorities.

PMID- 28444047
TI  - Health regionalization in Amazonas: progress and challenges.
AB  - This paper analyses the health services regionalization process in the State of
      Amazonas through a case study covering the health sub-region Manaus Surroundings.
      This is a qualitative, descriptive and analytical research, which data were
      collected using interviews, documents and Internet reviews, oriented by the
      guiding concept of health regionalization. Study findings revealed a social
      setting dominated by asymmetry, verticality, competitiveness and fragile
      multilateral relations among municipalities, associated to a bureaucratic profile
      of local institutions operating in the region under study. The political agents
      have limited acknowledgement of the sociopolitical and institutional conditions
      in which they operate. They usually impute healthcare networks' management and
      operational issues to the natural and geographical characteristics of the Amazon
      region, but their financing, governance and technical capacity are insufficient
      to overcome them.

PMID- 28444048
TI  - State health managers' perceptions of the Public Health Action Organizational
      Contract in the State of Ceara, Brazil.
AB  - The Public Health Action Organizational Contract (COAP) / Decree 7.508/2011 aimed
      to seal health agreements made between federated entities to promote the
      cooperative governance and management of Health Regions. A qualitative study was
      carried out adopting a hermeneutic approach to understand state health managers'
      perceptions of the elaboration and effects of the COAP in the State of Ceara.
      Open-ended interviewees and documental analysis were conducted. It was observed
      that the COAP led to the strengthening of regionalization in the government
      sphere; institutional gains through the implementation of ombudsmen and the
      National System of Pharmaceutical Care Management; increased information about
      the state health system's workforce; and health budget transparency. The
      following problems were (re)visited: institutional weakness in the operation of
      the network; limited state capacity for regulation of care; and underfunding.
      Regional governance was restricted to the government sphere, coordinated by the
      state, and was characterized by a predominantly bureaucratic and hierarchical
      governance structure. The COAP inaugurated a contractual interfederative model of
      regionalization, but revealed the institutional weaknesses of the SUS and its
      lacks of capacity to fulfill its principles as the structural problems of the
      three-tiered model go unaddressed.

PMID- 28444049
TI  - Healthcare financing, decentralization and regional health planning: federal
      transfers and the healthcare networks in Minas Gerais, Brazil.
AB  - The Decrees 4279/10 and 7508/11 established norms to guide health politics, with
      impacts on funding of the Middle and High Complexity Hospital and Outpatient. To
      verify the effects on the consolidation of care networks in Minas Gerais, we
      performed an analytical-descriptive study of the National Health Fund from 2006
      to 2014. We observed decentralization of responsibilities, accompanied of
      resources and innovative financing mechanisms, resulting expansion of the network
      care model. The federal government definitions suggest reduction of the autonomy
      and limitation of regional solutions.

PMID- 28444050
TI  - Ambulatory municipal regulation of the Unified Health System services in Rio de
      Janeiro: advances, limitations and challenges.
AB  - Federalism is basis of the Republic of Brazil which is made up of the union of
      states, municipalities and the Federal District, with the basic principle of
      political and administrative decentralization in all political, economic and
      social relations. In the health sector, the primary health care provider should
      be able to integrate all care that the patient receives through the coordination
      of health services. This article aims to evaluate the results of referrals for
      consultations and outpatient examinations in primary health care in the
      municipality of Rio de Janeiro, highlighting the advances, limitations and
      challenges for management at the local level. A quantitative study was designed
      using administrative databases from the Registry of National Health
      Establishments (CNES), the National Regulatory System (SISREG), and a linkage
      between them. Between 2011 and 2015, the number of scheduled procedures increased
      by 86%, reflecting the decentralization of outpatient regulation for family
      doctors. It can be inferred that there is no shortage of specialists for
      outpatient care in the city in almost all areas. There are actually artificial
      bottlenecks that arise as a result of the lack of regulation of most of the
      workload contracted in specialist areas, that is, the number of vacancies is
      smaller than the capacity of health services available in health units at the
      municipal, state, federal levels and those contracted by the Unified Health
      System (SUS).

PMID- 28444051
TI  - Analysis of the Unified Health System funding and expenditure in the
      municipalities of the "Rota dos Bandeirantes" health region, State of Sao Paulo,
      Brazil.
AB  - The national scenario of lack of resources in the Brazilian Unified Health System
      (SUS) has led to major differences in the municipalities funding models. Thus,
      this study aims to analyze SUS funding and expenditure in seven cities of the
      Rota dos Bandeirantes health region, State of Sao Paulo, SP, Brazil, from 2009 to
      2012. Settled expenditure indicators were collected from the Public Health
      Budgets Information System (SIOPS) for analysis, showing descriptive data with
      absolute and relative frequency calculations. We identified that the per capita
      income available for the city of Barueri is almost tenfold that of the city of
      Carapicuiba, and that Barueri's health expenditure per capita is more than double
      that of the regional average and almost fivefold that of Carapicuiba. The Federal
      Government is responsible for 95.4% of all funding to municipalities. Most of the
      available income of the municipalities in the region include their own taxes and
      state transfers. All the municipalities showed a significant positive trend, both
      for available income and health expenditure. The regional average of own revenue
      spent on health is 27.3%. Carapicuiba achieved a level of 37.5%, which is much
      higher than the minimum of 15% required by the Federal Constitution.

PMID- 28444052
TI  - Healthcare regions and their care networks: an organizational-systemic model for
      SUS.
AB  - This paper describes a comprehensive effort to develop studies regarding Brazil's
      Unified Healthcare System (SUS), as a result of the combination of public
      services in a network that follows a region-based rationale (tripartite
      organization). The SUS emerges from such an integration and should be organized
      as such. The intention is to demonstrate that this type of organization is
      essential, given that Brazil is organized as a Federation, and all three
      governmental levels are, in a broad sense, equally responsible for healthcare.
      Healthcare services and actions are a complex set of activities that are
      interconnected on behalf of citizen health, which is a global concept that cannot
      be split up. Services must follow this rationale and be organized as such. Thus,
      healthcare services must be systematically organized to serve everyone equally,
      regardless of where a citizen lives. This systemic organization requires
      permanent interaction between federative units to discuss and operationalize
      reference services, funding and other technical and administrative aspects. These
      are the essential elements that make the SUS so complex and demand it be
      organized regionally, as a network of healthcare services.

PMID- 28444053
TI  - A systematic review of the process of regionalization of Brazil's Unified Health
      System, SUS.
AB  - This review focuses only on specific studies into the SUS regionalization
      process, which were based on empirical results and published since 2006, when the
      SUS was already under the aegis of the Pact for Health framework. It was found
      that the regionalization process is now underway in all spheres of government,
      subject to a set of challenges common to the different realities of the country.
      These include, primarily, that committee-structured entities are valued as spaces
      for innovation, yet also strive to overcome the bureaucratic and clientelist
      political culture. Regional governance is further hampered by the fragmentation
      of the system and, in particular, by the historical deficiency in planning, from
      the local level to the strategic policies for technology incorporation. The
      analyses enabled the identification of a culture of broad privilege for political
      negotiation, to the detriment of planning, as one of the main factors responsible
      for a vicious circle that sustains technical deficiency in management.

PMID- 28444054
TI  - Regionalization in the Brazilian Healthcare System, SUS: a critical review.
AB  - Objective: to review the output and the use of the data to support managers in
      making decisions on the healthcare system, and analyze academic output on the
      theme. Method: An online search of the SciELO database for articles using
      'regionalization' and 'health/healthcare' as the keywords, and all indices as the
      'scope of the study'. We found a total of 102 references, and after analyzing the
      abstracts selected 70 articles that effectively discuss regionalization of
      health/healthcare in Brazil. We also found four articles in non-health related
      journals. Analysis: the institutional criteria (journal, theme area, date of
      publication, scope and number of authors), and the analytical criteria created by
      author - Type 1 - "Exploratory Studies" (26), "Evaluation Studies" (6),
      "Comparison Studies" (3); and "Reports of Experience" (5), Type 2 - "Theoretical
      Analytical" papers (20) and "Historical-Conceptual Reviews" (4), and Type 3 -
      "Editorials (3) and "Book Reviews" (3). Findings: regionalization has become more
      important in journals published since 2010. Most of the articles fall in the Type
      1 category.

PMID- 28444055
TI  - Prospects of studies on violence, adolescence and cortisol: a systematic
      literature review.
AB  - Violence has a negative impact on adolescents and affects their quality of life.
      It causes stress and requires the victim's adaptive capacity, which can cause
      psychological and biological changes. Hormone cortisol levels have been used as
      stress biomarker in several studies. This paper aims to perform a systematic
      literature review of publications on cortisol and violence involving teenagers
      from 2000 to 2013. Descriptors "cortisol", "violence" and "adolescent" were used
      in both English and Portuguese in this review, which included bibliographic
      databases PubMed/Medline, Lilacs, BVS and SciELO. Twelve papers were analyzed.
      Most studies involve participants from the United States, of both genders and
      without a control group. Different types of violence are studied, especially
      family violence, victimization or testimony. All studies used saliva to measure
      cortisol and no standard methodology was used for the analysis. Most studies
      (83.3%) found a statistically significant association between cortisol levels and
      exposure to violence. Results regarding gender, type of violence, socioeconomic
      status or cortisol analysis methods are not yet uniform.

PMID- 28444056
TI  - Care for young victims of assault in public emergency services in 2011: Sex
      differences.
AB  - This article aims to describe the characteristics of assaults among youth victims
      of violence treated in Public Emergency Departments, according to sex. This is a
      descriptive study using data from the Brazilian Violence and Accidents
      Surveillance System based on a multicenter survey conducted by the Ministry of
      Health in 71 public emergency departments, located in 24 state capitals and the
      Federal District in 2011. Male subjects predominated among the victims (75.1%)
      and also among aggressors (83.1% and 69.7% of cases of violence against male and
      female victims, respectively). Among female victims, episodes of violence were
      more frequent at home (43.6%). The perpetrator was a stranger in 49.7% and 26.8%
      of cases among male and female victims, respectively, while the perpetrator was a
      partner or ex-partner in 3.9% and 31.5% cases, respectively (p < 0.001). Greater
      severity of injuries among men was consistent with the higher proportion of
      deaths in the first 24 hours (2.1%) compared to women (0.2%) (p < 0.001). The
      violence profile among youth victims treated in Public Emergency Departments was
      substantially different according to the sex of the victims. The results
      highlight the need to implement intersectoral policies, in line with the
      Brazilian Youth Statute.

PMID- 28444057
TI  - Determinant factors of knowledge, attitudes and practices regarding STD/AIDS and
      viral hepatitis among youths aged 18 to 29 years in Brazil.
AB  - The scope of this study was to evaluate the vulnerability of Brazilian youths to
      STDs/HIV&AIDS and Viral Hepatitis. Interviews were conducted with 1,208 youths
      aged 18 to 29 in 15 states and the Federal District. The regional and national
      adjusted margin of error of the research was 2.8%. The study was approved by the
      School of Medicine of Brasilia University with support from PAHO and the Ministry
      of Health. A scale with 35 questions (knowledge, attitudes and practices) was the
      main dependent variable. Adjusted linear regression models identified the
      demographic and social determinant factors that explain scale variations. The
      scale attained a satisfactory level of consistency (Cronbach's Alpha: 0.689).
      Sociodemographic factors associated to scale variations include gender, race,
      education and civil status. Social determinants associated to scale variations
      include frequency of discussions about sexuality with parents and health
      professionals, alcohol consumption, leisure and being part of a social movement,
      access to the internet, interest in learning and having the father and/or teacher
      as a personal reference. Brazilian youths are vulnerable to the transmission of
      STDs/HIV&AIDS. Public policies are needed to promote the engagement of parents
      and teachers in issues related to sexuality.

PMID- 28444058
TI  - [Quality of life with Obsessive-Compulsive Disorder: a study among Primary Care
      users].
AB  - Quality of life (QOL) can be affected by the presence of mental disorders, like
      Obsessive-Compulsive Disorder (OCD). Thus, the evaluation and monitoring of QOL
      in patients with mental disorders enables the identification of priorities,
      making it possible to implement actions to improve QOL among health system users.
      The scope of this article is to measure QOL in OCD patients in primary health
      care. It involves a cross-sectional study with a convenience sample including all
      users of three Basic Health Units of Pelotas in the State of Rio Grande do Sul,
      Brazil. The quality of life was measured with the WHOQOL-Bref and the OCD was
      assessed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) This
      study included 1081 individuals. The prevalence of OCD was 3.9%. OCD patients had
      a lower average in all domains of QOL when compared to individuals without OCD (p
      < 0.001). The findings of this study emphasize the importance of using QOL as a
      monitoring tool of the disorder in basic health care.

PMID- 28444059
TI  - [Anthropometric profile of children in accordance with the structure of daycare
      centers].
AB  - The scope of this article is to evaluate the structure of public daycare centers
      and the anthropometric profile of children in the city of Campina Grande in the
      State of Paraiba, Brazil. It is a cross-sectional study that involved 793
      children attended in daycare centers. Information to describe the daycare centers
      were included (structure related to the capacity of demand and the processing
      power of school meals, reception system of children, location area) and the
      anthropometric status of the children (Height/Age, Weight/Height). The mean Z
      scores for Height/Age and Weight/Height were lower among children from daycare
      centers with a greater number of children per employee, attended on a part time
      basis and located in the rural zone. The Z-scores for Height/Age were also lower
      among children who studied in classrooms and were housed in rest rooms with a
      greater density of children. Problems were detected in the structure of daycare
      centers with respect to the capacity of human resources to look after the
      children and the ways of living together (coexistence), which can make a
      difference in the nutritional status of the children. For its part, full-time
      daycare attendance and urbanization predispose children positively to growth.

PMID- 28444060
TI  - [Personal and social factors that influence subjective well-being: socioeconomic
      differences].
AB  - The main objective is to study the relation and impact of Socioeconomic Status
      (SES) on the subjective well-being in children and adolescents and the role of
      social and personal factors in this relation. Data was collected in 16 schools; 8
      in the North and 8 in the Lisbon Region of Portugal. The questionnaires were
      filled out by 1,181 youths, 51.5% of which were female. Ages ranged between 8 and
      17, the girl's average age being 9.8 years (SD = 1.32) and the boy's average age
      being 10.0 (SD = 1.53); 2.6% of young people had special educational needs, and
      3% did not use the Portuguese language at home; 12.2% had repeated a grade; 27.1%
      had a high SES; 64.2% had medium/low SES and 8.7% were unemployed. Three adequate
      regression models were built. Model 1 established the association between SES and
      subjective well-being. This association turned out to be not significant with the
      effect of personal and social factors, which were strongly associated with
      subjective wellbeing. It was revealed that the impact of SES on subjective well
      being is mitigated by the presence of social and personal factors. The promotion
      of personal and social skills appears to be an effective way to avoid the
      negative effects of low SES in child and adolescent development.

PMID- 28444061
TI  - ?
AB  - [This corrects the article doi: 10.1590/1413-81232015212.19422015].

PMID- 28444062
TI  - Prognostic Value of Coronary Flow Reserve Obtained on Dobutamine Stress
      Echocardiography and its Correlation with Target Heart Rate.
AB  - Background:: Normal coronary flow velocity reserve (CFVR) (>= 2) obtained in the
      left anterior descending coronary artery (LAD) from transthoracic
      echocardiography is associated with a good prognosis, but there is no study
      correlating CFVR with submaximal target heart rate (HR). Objective:: To evaluate
      the prognostic value of CFVR obtained in the LAD of patients with preserved
      (>50%) left ventricular ejection fraction (LVEF) who completed a dobutamine
      stress echocardiography (DSE), considering target HR. Methods:: Prospective study
      of patients with preserved LVEF and CFVR obtained in the LAD who completed DSE.
      In Group I (GI = 31), normal CFVR was obtained before achieving target HR, and,
      in Group II (GII = 28), after that. Group III (G III=24) reached target HR, but
      CFVR was abnormal. Death, acute coronary insufficiency, coronary intervention,
      coronary angiography without further intervention, and hospitalization were
      considered events. Results:: In 28 +/- 4 months, there were 18 (21.6%) events: 6%
      (2/31) in GI, 18% (5/28) in GII, and 46% (11/24) in GIII. There were 4 (4.8%)
      deaths, 6 (7.2%) coronary interventions and 8 (9.6%) coronary angiographies
      without further intervention. In event-free survival by regression analysis, GIII
      had more events than GI (p < 0.001) and GII (p < 0.045), with no difference
      between GI and GII (p = 0.160). After adjustment, the only difference was between
      GIII and GI (p = 0.012). Conclusion:: In patients with preserved LVEF and who
      completed their DSE, normal CFVR obtained before achieving target HR was
      associated with better prognosis. Fundamento:: A reserva de velocidade de fluxo
      coronariano (RVFC) adequada (>= 2) obtida na arteria descendente anterior (ADA)
      atraves do ecocardiograma transtoracico associa-se a bom prognostico, mas nao ha
      estudo correlacionando-a com a frequencia cardiaca (FC) alvo (submaxima).
      Objetivo:: Avaliar o valor prognostico da RVFC obtida na ADA de pacientes com
      fracao de ejecao do ventriculo esquerdo (FEVE) preservada (>50%) e ecocardiograma
      sob estresse com dobutamina (EED) concluido, considerando a FC alvo submaxima.
      Metodos:: studo prospectivo de pacientes com FEVE preservada e RVFC obtida na ADA
      durante EED concluido. No Grupo I (GI=31), a RVFC adequada foi obtida antes de se
      atingir a FC alvo, e no Grupo II (G II=28), apos. O Grupo III (G III=24) atingiu
      a FC alvo, mas a RVFC foi inadequada. Foram considerados eventos: obito,
      insuficiencia coronariana aguda, intervencao coronariana, coronariografia sem
      intervencao subsequente e internamento hospitalar. Resultados:: Em 28 +/- 4
      meses, ocorreram 18 (21,6%) eventos, sendo 6% (2/31) no GI, 18% (5/28) no GII e
      46% (11/24) no GIII. Foram 4 (4,8%) obitos, 6 (7,2%) intervencoes coronarianas e
      8 (9,6%) coronariografias sem intervencao subsequente. Na sobrevida livre de
      eventos pela analise de regressao, GIII apresentou mais eventos do que GI (p <
      0,001) ou GII (p < 0,045), nao havendo diferenca entre GI e GII (p = 0,160). Apos
      o ajustamento, foi mantida a diferenca apenas entre GIII e GI (p = 0,012).
      Conclusao:: Em pacientes com FEVE preservada e EED concluido, a RVFC adequada
      obtida antes da FC alvo associou-se ao melhor prognostico.

PMID- 28444063
TI  - Effect of Lactation on myocardial vulnerability to ischemic insult in rats.
AB  - Background: Cardiovascular diseases are the leading cause of mortality and long
      term disability worldwide. Various studies have suggested a protective effect of
      lactation in reducing the risk of cardiovascular diseases. Objective: This study
      was designed to assess the effects of pregnancy and lactation on the
      vulnerability of the myocardium to an ischemic insult. Methods: Eighteen female
      rats were randomly divided into three groups: ischemia-reperfusion (IR), in which
      the hearts of virgin rats underwent IR (n = 6); lactating, in which the rats
      nursed their pups for 3 weeks and the maternal hearts were then submitted to IR
      (n = 6); and non-lactating, in which the pups were separated after birth and the
      maternal hearts were submitted to IR (n = 6). Outcome measures included heart
      rate (HR), left ventricular developed pressure (LVDP), rate pressure product
      (RPP), ratio of the infarct size to the area at risk (IS/AAR %), and ventricular
      arrhythmias - premature ventricular contraction (PVC) and ventricular tachycardia
      (VT). Results: The IS/AAR was markedly decreased in the lactating group when
      compared with the non-lactating group (13.2 +/- 2.5 versus 39.7 +/- 3.5, p <
      0.001) and the IR group (13.2 +/- 2.5 versus 34.0 +/- 4.7, p < 0.05). The
      evaluation of IR-induced ventricular arrhythmias indicated that the number of
      compound PVCs during ischemia, and the number and duration of VTs during ischemia
      and in the first 5 minutes of reperfusion in the non-lactating group were
      significantly (p < 0.05) higher than those in the lactating and IR groups.
      Conclusion: Lactation induced early-onset cardioprotective effects, while rats
      that were not allowed to nurse their pups were more susceptible to myocardial IR
      injury.

PMID- 28444064
TI  - Assessment of Carotid Intima-Media Thickness as an Early Marker Of Vascular
      Damage In Hypertensive Children.
AB  - Background: The increased carotid intima-media thickness (CIMT) correlates with
      the presence of atherosclerosis in adults and describes vascular abnormalities in
      both hypertensive children and adolescents. Objective: To assess CIMT as an early
      marker of atherosclerosis and vascular damage in hypertensive children and
      adolescents compared with non-hypertensive controls and to evaluate the influence
      of gender, age, and body mass index (BMI) on CIMT on each group. Methods:
      Observational cohort study. A total of 133 hypertensive subjects (male, n = 69;
      mean age, 10.5 +/- 4 years) underwent carotid ultrasound exam for assessment of
      CIMT. One hundred and twenty-one non-hypertensive subjects (male, n = 64; mean
      age, 9.8 +/- 4.1 years) were selected as controls for gender, age (+/- 1 year),
      and BMI (+/- 10%). Results: There were no significant difference regarding gender
      (p = 0.954) and age (p = 0.067) between groups. Hypertensive subjects had higher
      BMI when compared to control group (p = 0.004), although within the established
      range of 10%. Subjects in the hypertensive group had higher CIMT values when
      compared to control group (0.46 +/- 0.05 versus 0.42 +/- 0.05 mm, respectively, p
      < 0.001; one-way ANOVA). Carotid IMT values were not significantly influenced by
      gender, age, and BMI when analyzed in both groups separately (Student's t-test
      for independent samples). According to the adjusted determination coefficient
      (R2) only 11.7% of CIMT variations were accounted for by group variations,
      including age, gender, and BMI. Conclusions: Carotid intima-media thickness was
      higher in hypertensive children and adolescents when compared to the control
      group. The presence of hypertension increased CIMT regardless of age, gender, and
      BMI.

PMID- 28444065
TI  - beta-blockers in septic shock: are we there yet?

PMID- 28444066
TI  - Dear Sepsis-3, we are sorry to say that we don't like you.

PMID- 28444067
TI  - Seeking to humanize intensive care.

PMID- 28444068
TI  - Acute bag-valve breathing maneuvers plus manual chest compression is safe during
      stable septic shock: a randomized clinical trial.
AB  - Objective:: To evaluate the effects of bag-valve breathing maneuvers combined
      with standard manual chest compression techniques on safety, hemodynamics and
      oxygenation in stable septic shock patients. Design:: A parallel, assessor
      blinded, randomized trial of two groups. A computer-generated list of random
      numbers was prepared by an independent researcher to allocate treatments.
      Setting:: The Intensive Care Unit at Hospital Sao Lucas, Pontificia Universidade
      Catolica do Rio Grande do Sul. Participants:: Fifty-two subjects were assessed
      for eligibility, and 32 were included. All included subjects (n = 32) received
      the allocated intervention (n = 19 for the Experimental Group and n = 13 for the
      Control Group). Intervention:: Twenty minutes of bag-valve breathing maneuvers
      combined with manual chest compression techniques (Experimental Group) or chest
      compression, as routinely used at our intensive care unit (Control Group). Follow
      up was performed immediately after and at 30 minutes after the intervention. Main
      outcome measure:: Mean artery pressure. Results:: All included subjects completed
      the trial (N = 32). We found no relevant effects on mean artery pressure (p =
      0.17), heart rate (p = 0.50) or mean pulmonary artery pressure (p = 0.89) after
      adjusting for subject age and weight. Both groups were identical regarding oxygen
      consumption after the data adjustment (p = 0.84). Peripheral oxygen saturation
      tended to increase over time in both groups (p = 0.05), and there was no
      significant association between cardiac output and venous oxygen saturation (p =
      0.813). No clinical deterioration was observed. Conclusion:: A single session of
      bag-valve breathing maneuvers combined with manual chest compression is
      hemodynamically safe for stable septic-shocked subjects over the short-term.

PMID- 28444069
TI  - Predictors and pattern of weaning and long-term outcome of patients with
      prolonged mechanical ventilation at an acute intensive care unit in North India.
AB  - Objective:: This study aimed to examine the clinical characteristics, weaning
      pattern, and outcome of patients requiring prolonged mechanical ventilation in
      acute intensive care unit settings in a resource-limited country. Methods:: This
      was a prospective single-center observational study in India, where all adult
      patients requiring prolonged ventilation were followed for weaning duration and
      pattern and for survival at both intensive care unit discharge and at 12 months.
      The definition of prolonged mechanical ventilation used was that of the National
      Association for Medical Direction of Respiratory Care. Results:: During the one
      year period, 49 patients with a mean age of 49.7 years had prolonged ventilation;
      63% were male, and 84% had a medical illness. The median APACHE II and SOFA
      scores on admission were 17 and 9, respectively. The median number of ventilation
      days was 37. The most common reason for starting ventilation was respiratory
      failure secondary to sepsis (67%). Weaning was initiated in 39 (79.5%) patients,
      with success in 34 (87%). The median weaning duration was 14 (9.5 - 19) days, and
      the median length of intensive care unit stay was 39 (32 - 58.5) days. Duration
      of vasopressor support and need for hemodialysis were significant independent
      predictors of unsuccessful ventilator liberation. At the 12-month follow-up, 65%
      had survived. Conclusion:: In acute intensive care units, more than one-fourth of
      patients with invasive ventilation required prolonged ventilation. Successful
      weaning was achieved in two-thirds of patients, and most survived at the 12-month
      follow-up.

PMID- 28444070
TI  - Brazilian version of the Functional Status Score for the ICU: translation and
      cross-cultural adaptation.
AB  - Objective:: The aim of the present study was to translate and cross-culturally
      adapt the Functional Status Score for the intensive care unit (FSS-ICU) into
      Brazilian Portuguese. Methods:: This study consisted of the following steps:
      translation (performed by two independent translators), synthesis of the initial
      translation, back-translation (by two independent translators who were unaware of
      the original FSS-ICU), and testing to evaluate the target audience's
      understanding. An Expert Committee supervised all steps and was responsible for
      the modifications made throughout the process and the final translated version.
      Results:: The testing phase included two experienced physiotherapists who
      assessed a total of 30 critical care patients (mean FSS-ICU score = 25 +/- 6). As
      the physiotherapists did not report any uncertainties or problems with
      interpretation affecting their performance, no additional adjustments were made
      to the Brazilian Portuguese version after the testing phase. Good interobserver
      reliability between the two assessors was obtained for each of the 5 FSS-ICU
      tasks and for the total FSS-ICU score (intraclass correlation coefficients ranged
      from 0.88 to 0.91). Conclusion:: The adapted version of the FSS-ICU in Brazilian
      Portuguese was easy to understand and apply in an intensive care unit
      environment.

PMID- 28444071
TI  - Reducing pressure ulcers in patients with prolonged acute mechanical ventilation:
      a quasi-experimental study.
AB  - Objective:: To determine the effectiveness of a quality management program in
      reducing the incidence and severity of pressure ulcers in critical care patients.
      Methods:: This was a quasi-experimental, before-and-after study that was
      conducted in a medical-surgical intensive care unit. Consecutive patients who had
      received mechanical ventilation for >= 96 hours were included. A "Process
      Improvement" team designed a multifaceted interventional process that consisted
      of an educational session, a pressure ulcer checklist, a smartphone application
      for lesion monitoring and decision-making, and a "family prevention bundle".
      Results:: Fifty-five patients were included in Pre-I group, and 69 were included
      in the Post-I group, and the incidence of pressure ulcers in these groups was 41
      (75%) and 37 (54%), respectively. The median time for pressure ulcers to develop
      was 4.5 [4 - 5] days in the Pre-I group and 9 [6 - 20] days in the Post-I group
      after admission for each period. The incidence of advanced-grade pressure ulcers
      was 27 (49%) in the Pre-I group and 7 (10%) in the Post-I group, and finally, the
      presence of pressure ulcers at discharge was 38 (69%) and 18 (26%), respectively
      (p < 0.05 for all comparisons). Family participation totaled 9% in the Pre-I
      group and increased to 57% in the Post-I group (p < 0.05). A logistic regression
      model was used to analyze the predictors of advanced-grade pressure ulcers. The
      duration of mechanical ventilation and the presence of organ failure were
      positively associated with the development of pressure ulcers, while the
      multifaceted intervention program acted as a protective factor. Conclusion:: A
      quality program based on both a smartphone application and family participation
      can reduce the incidence and severity of pressure ulcers in patients on prolonged
      acute mechanical ventilation.

PMID- 28444072
TI  - Chronic obstructive pulmonary disease exacerbation in the intensive care unit:
      clinical, functional and quality of life at discharge and 3 months of follow up.
AB  - Objective:: The purpose of this study was to evaluate the clinical/functional
      aspects and quality of life of chronic obstructive pulmonary disease patients who
      were discharged after an intensive care unit admission for acute respiratory
      failure. Methods:: This prospective study included chronic obstructive pulmonary
      disease patients who were admitted to two intensive care units between December
      of 2010 and August of 2011 and evaluated over three visits after discharge.
      Thirty patients were included, and 20 patients completed the three-month follow
      up. Results:: There was a significant improvement in the following: forced
      expiratory flow in one second (L) (1.1/1.4/1.4; p = 0.019), six-minute walk test
      (m) (- /232.8 /272.6; p = 0.04), BODE score (7.5/5.0/3.8; p = 0.001), cognition
      measured by the Mini Mental State Examination (21/23.5/23.5; p = 0.008) and
      quality of life measured by the total Saint George Respiratory Questionnaire
      score (63.3/56.8/51, p = 0.02). The mean difference in the total score was 12.3
      (between visits 1 and three). Important clinical differences were observed for
      the symptom score (18.8), activities score (5.2) and impact score (14.3). The
      majority of participants (80%) reported they would be willing to undergo a new
      intensive care unit admission. Conclusion:: Despite the disease severity, there
      was a significant clinical, functional and quality of life improvement at the end
      of the third month. Most patients would be willing to undergo a new intensive
      care unit admission.

PMID- 28444073
TI  - Antibacterial activity of standard and N-doped titanium dioxide-coated
      endotracheal tubes: an in vitro study.
AB  - Objective:: The aim of this study was to assess the antibacterial activity
      against Staphylococcus aureus and Pseudomonas aeruginosa of two nanoparticle
      endotracheal tube coatings with visible light-induced photocatalysis. Methods::
      Two types of titanium dioxide nanoparticles were tested: standard anatase (TiO2)
      and N-doped TiO2 (N-TiO2). Nanoparticles were placed on the internal surface of a
      segment of commercial endotracheal tubes, which were loaded on a cellulose
      acetate filter; control endotracheal tubes were left without a nanoparticle
      coating. A bacterial inoculum of 150 colony forming units was placed in the
      endotracheal tubes and then exposed to a fluorescent light source (3700 lux, 300
      700 nm wavelength) for 5, 10, 20, 40, 60 and 80 minutes. Colony forming units
      were counted after 24 hours of incubation at 37 degrees C. Bacterial inactivation
      was calculated as the percentage reduction of bacterial growth compared to
      endotracheal tubes not exposed to light. Results:: In the absence of light, no
      relevant antibacterial activity was shown against neither strain. For P.
      aeruginosa, both coatings had a higher bacterial inactivation than controls at
      any time point (p < 0.001), and no difference was observed between TiO2 and N
      TiO2. For S. aureus, inactivation was higher than for controls starting at 5
      minutes for N-TiO2 (p = 0.018) and 10 minutes for TiO2 (p = 0.014); inactivation
      with N-TiO2 was higher than that with TiO2 at 20 minutes (p < 0.001), 40 minutes
      (p < 0.001) and 60 minutes (p < 0.001). Conclusions:: Nanosized commercial and N
      doped TiO2 inhibit bacterial growth under visible fluorescent light. N-TiO2 has
      higher antibacterial activity against S. aureus compared to TiO2.

PMID- 28444074
TI  - Prognostic impact of the time of admission and discharge from the intensive care
      unit.
AB  - Objective:: To determine the impact of the day and time of admission and
      discharge from the intensive care unit on mortality. Methods:: Prospective
      observational study that included patients admitted to the intensive care unit of
      the Hospital Maciel in Montevideo between April and November 2014. Results:: We
      analyzed 325 patients with an average age of 55 (36 - 71) years and a SAPS II
      value of 43 (29 - 58) points. No differences were found in the mortality of
      patients in the intensive care unit when time of admission (35% on the weekend
      versus 31% on weekdays, p = ns) or the hour of entry (35% at night versus 31% in
      the daytime, p = ns) were compared. The time of discharge was associated with
      higher hospital mortality rates (57% for weekend discharges versus 14% for
      weekday discharges, p = 0.000). The factors independently associated with
      hospital mortality after discharge from the intensive care unit were age > 50
      years (OR 2.4, 95%CI, 1.1 - 5.4) and weekend discharge (OR 7.7, 95%CI, 3.8-15.6).
      Conclusion:: This study identified the time of discharge from the intensive care
      unit as a factor that was independently associated with hospital mortality.

PMID- 28444075
TI  - Applicability of respiratory variations in stroke volume and its surrogates for
      dynamic fluid responsiveness prediction in critically ill patients: a systematic
      review of the prevalence of required conditions.
AB  - Objective:: The present systematic review searched for published data on the
      prevalence of required conditions for proper assessment in critically ill
      patients. Methods:: The Medline, Scopus and Web of Science databases were
      searched to identify studies that evaluated the prevalence of validated
      conditions for the fluid responsiveness assessment using respiratory variations
      in the stroke volume or another surrogate in adult critically ill patients. The
      primary outcome was the suitability of the fluid responsiveness evaluation. The
      secondary objectives were the type and prevalence of pre-requisites evaluated to
      define the suitability. Results:: Five studies were included (14,804 patients).
      High clinical and statistical heterogeneity was observed (I2 = 98.6%), which
      prevented us from pooling the results into a meaningful summary conclusion. The
      most frequent limitation identified is the absence of invasive mechanical
      ventilation with a tidal volume >= 8mL/kg. The final suitability for the fluid
      responsiveness assessment was low (in four studies, it varied between 1.9 to
      8.3%, in one study, it was 42.4%). Conclusion:: Applicability of the dynamic
      indices of preload responsiveness requiring heart-lung interactions might be
      limited in daily practice.

PMID- 28444076
TI  - Variable mechanical ventilation.
AB  - Objective:: To review the literature on the use of variable mechanical
      ventilation and the main outcomes of this technique. Methods:: Search, selection,
      and analysis of all original articles on variable ventilation, without
      restriction on the period of publication and language, available in the
      electronic databases LILACS, MEDLINE(r), and PubMed, by searching the terms
      "variable ventilation" OR "noisy ventilation" OR "biologically variable
      ventilation". Results:: A total of 36 studies were selected. Of these, 24 were
      original studies, including 21 experimental studies and three clinical studies.
      Conclusion:: Several experimental studies reported the beneficial effects of
      distinct variable ventilation strategies on lung function using different models
      of lung injury and healthy lungs. Variable ventilation seems to be a viable
      strategy for improving gas exchange and respiratory mechanics and preventing lung
      injury associated with mechanical ventilation. However, further clinical studies
      are necessary to assess the potential of variable ventilation strategies for the
      clinical improvement of patients undergoing mechanical ventilation.

PMID- 28444077
TI  - Chronic critical illness: are we saving patients or creating victims?
AB  - The technological advancements that allow support for organ dysfunction have led
      to an increase in survival rates for the most critically ill patients. Some of
      these patients survive the initial acute critical condition but continue to
      suffer from organ dysfunction and remain in an inflammatory state for long
      periods of time. This group of critically ill patients has been described since
      the 1980s and has had different diagnostic criteria over the years. These
      patients are known to have lengthy hospital stays, undergo significant
      alterations in muscle and bone metabolism, show immunodeficiency, consume
      substantial health resources, have reduced functional and cognitive capacity
      after discharge, create a sizable workload for caregivers, and present high long
      term mortality rates. The aim of this review is to report on the most current
      evidence in terms of the definition, pathophysiology, clinical manifestations,
      treatment, and prognosis of persistent critical illness.

PMID- 28444078
TI  - Expiratory rib cage compression in mechanically ventilated adults: systematic
      review with meta-analysis.
AB  - Objective:: To review the literature on the effects of expiratory rib cage
      compression on ventilatory mechanics, airway clearance, and oxygen and
      hemodynamic indices in mechanically ventilated adults. Methods:: Systematic
      review with meta-analysis of randomized clinical trials in the databases MEDLINE
      (via PubMed), EMBASE, Cochrane CENTRAL, PEDro, and LILACS. Studies on adult
      patients hospitalized in intensive care units and under mechanical ventilation
      that analyzed the effects of expiratory rib cage compression with respect to a
      control group (without expiratory rib cage compression) and evaluated the
      outcomes static and dynamic compliance, sputum volume, systolic blood pressure,
      diastolic blood pressure, mean arterial pressure, heart rate, peripheral oxygen
      saturation, and ratio of arterial oxygen partial pressure to fraction of inspired
      oxygen were included. Experimental studies with animals and those with incomplete
      data were excluded. Results:: The search strategy produced 5,816 studies, of
      which only three randomized crossover trials were included, totaling 93 patients.
      With respect to the outcome of heart rate, values were reduced in the expiratory
      rib cage compression group compared with the control group [-2.81 bpm (95%
      confidence interval [95%CI]: -4.73 to 0.89; I2: 0%)]. Regarding dynamic
      compliance, there was no significant difference between groups [-0.58mL/cmH2O
      (95%CI: -2.98 to 1.82; I2: 1%)]. Regarding the variables systolic blood pressure
      and diastolic blood pressure, significant differences were found after
      descriptive evaluation. However, there was no difference between groups regarding
      the variables secretion volume, static compliance, ratio of arterial oxygen
      partial pressure to fraction of inspired oxygen, and peripheral oxygen
      saturation. Conclusion:: There is a lack of evidence to support the use of
      expiratory rib cage compression in routine care, given that the literature on
      this topic offers low methodological quality and is inconclusive.

PMID- 28444079
TI  - Use of noninvasive ventilation in severe acute respiratory distress syndrome due
      to accidental chlorine inhalation: a case report.
AB  - Acute respiratory distress syndrome is characterized by diffuse inflammatory lung
      injury and is classified as mild, moderate, and severe. Clinically, hypoxemia,
      bilateral opacities in lung images, and decreased pulmonary compliance are
      observed. Sepsis is one of the most prevalent causes of this condition (30 -
      50%). Among the direct causes of acute respiratory distress syndrome, chlorine
      inhalation is an uncommon cause, generating mucosal and airway irritation in most
      cases. We present a case of severe acute respiratory distress syndrome after
      accidental inhalation of chlorine in a swimming pool, with noninvasive
      ventilation used as a treatment with good response in this case. We classified
      severe acute respiratory distress syndrome based on an oxygen partial
      pressure/oxygen inspired fraction ratio <100, although the Berlin classification
      is limited in considering patients with severe hypoxemia managed exclusively with
      noninvasive ventilation. The failure rate of noninvasive ventilation in cases of
      acute respiratory distress syndrome is approximately 52% and is associated with
      higher mortality. The possible complications of using noninvasive positive
      pressure mechanical ventilation in cases of acute respiratory distress syndrome
      include delays in orotracheal intubation, which is performed in cases of poor
      clinical condition and with high support pressure levels, and deep inspiratory
      efforts, generating high tidal volumes and excessive transpulmonary pressures,
      which contribute to ventilation-related lung injury. Despite these complications,
      some studies have shown a decrease in the rates of orotracheal intubation in
      patients with acute respiratory distress syndrome with low severity scores,
      hemodynamic stability, and the absence of other organ dysfunctions.

PMID- 28444080
TI  - Rhabdomyolysis as a manifestation of a metabolic disease: a case report.
AB  - Rhabdomyolysis is a process of muscle destruction that can present with varying
      clinical manifestations. In pediatric patients, its main etiology is infectious
      diseases. We present a previously healthy adolescent who was admitted to our
      emergency department with a four-day history of myalgia, muscle weakness and dark
      urine. At presentation, she was dehydrated. Blood analysis revealed acute renal
      failure and increased muscular enzymes. She was transferred to our pediatric
      intensive care unit. Medical therapies for correction of dehydration and the
      ionic and metabolic consequences of renal failure were performed. Due to
      oliguria, renal replacement therapy was initiated. An etiological investigation
      revealed a beta-oxidation defect. Metabolic diseases are a known cause of
      rhabdomyolysis. Muscular destruction should be diagnosed early in order to avoid
      its potential consequences. Generally, the treatment of rhabdomyolysis is
      conservative, although in some situations, a more invasive approach is needed.

PMID- 28444081
TI  - High prevalence of burnout syndrome among intensivists of the city of Porto
      Alegre.

PMID- 28444083
TI  - Interictal abnormal fMRI activation of visual areas during a motor task cued by
      visual stimuli in migraine.
AB  - Objective: To assess changes in blood-oxygen-level-dependent activity after light
      deprivation compared to regular light exposure in subjects with migraine in the
      interictal state and in controls. Methods: Ten subjects with migraine and ten
      controls participated in two sessions of functional magnetic resonance imaging.
      In each session, they performed a finger-tapping task with the right hand, cued
      by visual stimuli. They were scanned before and after 30 minutes of light
      deprivation or light exposure. In subjects with migraine, functional magnetic
      resonance imaging was performed interictally. Analysis of variance was made with
      the factors time (before or after), session (light deprivation or exposure), and
      group (migraine or control). Results: There were significant "group" effects in a
      cluster in the bilateral cuneus encompassing the superior border of the calcarine
      sulcus and extrastriate cortex. There were no significant effects of "time",
      "session", or interactions between these factors. Conclusion: The main result of
      this study is consistent with aberrant interictal processing of visual
      information in migraine. Light deprivation did not modulate functional magnetic
      resonance imaging activity in subjects with or without migraine. Objetivo:
      Avaliar mudancas na atividade cerebral por meio de ressonancia magnetica
      funcional apos privacao luminosa comparada a exposicao a luz, em individuos com
      enxaqueca no estado interictal e em controles. Metodos: Dez individuos com
      enxaqueca e dez controles participaram de duas sessoes de ressonancia magnetica
      funcional. Em cada sessao, realizaram uma tarefa motora com a mao direita guiada
      por estimulos visuais. Foram colhidas imagens antes e apos 30 minutos de privacao
      luminosa ou exposicao a luz. Em individuos com enxaqueca, a ressonancia funcional
      foi realizada no periodo interictal. Foi feita a analise de variancia com fatores
      tempo (antes ou depois), sessao (privacao ou exposicao a luz) e grupo (enxaqueca
      ou controle). Resultados: Houve efeitos significativos de "grupo" em uma area no
      cuneo bilateral, incluindo a borda superior do sulco calcarino e o cortex
      extraestriado. Nao houve efeitos significativos de "tempo", "sessao" ou
      interacoes entre estes fatores. Conclusao: O principal resultado deste estudo
      sugere um processamento interictal anormal das informacoes visuais em individuos
      com enxaqueca. A privacao luminosa nao modulou a atividade na ressonancia
      magnetica funcional em individuos com ou sem enxaqueca.

PMID- 28444084
TI  - Effects of zinc supplementation on fatigue and quality of life in patients with
      colorectal cancer.
AB  - Objective: To investigate the effects of oral zinc supplementation on fatigue
      intensity and quality of life of patients during chemotherapy for colorectal
      cancer. Methods: A prospective, randomized, double-blinded, placebo-controlled
      study was conducted with 24 patients on chemotherapy for colorectal
      adenocarcinoma in a tertiary care public hospital. The study patients received
      zinc capsules 35mg (Zinc Group, n=10) or placebo (Placebo Group, n=14) orally,
      twice daily (70mg/day), for 16 weeks, from the immediate postoperative period to
      the fourth chemotherapy cycle. Approximately 45 days after surgical resection of
      the tumor, all patients received a chemotherapeutic regimen. Before each of the
      four cycles of chemotherapy, the Functional Assessment of Chronic Illness Therapy
      Fatigue scale was completed. We used a linear mixed model for longitudinal data
      for statistical analysis. Results: The scores of quality of life and fatigue
      questionnaires were similar between the groups during the chemotherapy cycles.
      The Placebo Group presented worsening of quality of life and increased fatigue
      between the first and fourth cycles of chemotherapy, but there were no changes in
      the scores of quality of life or fatigue in the Zinc Group. Conclusion: Zinc
      supplementation prevented fatigue and maintained quality of life of patients with
      colorectal cancer on chemotherapy. Objetivo: Investigar os efeitos da
      suplementacao oral de zinco sobre a intensidade da fadiga e a qualidade de vida
      de pacientes durante a quimioterapia para neoplasia colorretal. Metodos: Estudo
      prospectivo, randomizado, controlado e duplo-cego conduzido em um hospital
      universitario publico terciario, com 24 pacientes em regime quimioterapico para
      adenocarcinoma colorretal. Os pacientes receberam capsulas de zinco 35mg (Grupo
      Zinco, n=10) ou placebo (Grupo Placebo, n=14) por via oral, duas vezes ao dia
      (70mg/dia), durante 16 semanas, desde o periodo pos-operatorio imediato ate o
      quarto ciclo de quimioterapia. Todos os pacientes receberam quimioterapia por
      aproximadamente 45 dias apos a resseccao cirurgica do tumor. A escala Functional
      Assessment of Chronic Illness Therapy-Fatigue foi preenchida antes de cada um dos
      quatro ciclos de quimioterapia. Utilizou-se o modelo de regressao linear misto
      para dados longitudinais para analise estatistica. Resultados: Os escores de
      qualidade de vida e de fadiga foram semelhantes entre os grupos de estudo durante
      os ciclos de quimioterapia. O Grupo Placebo apresentou piora da qualidade de vida
      e da fadiga entre o primeiro e o quarto ciclos de quimioterapia, mas nao houve
      mudanca nos escores de qualidade de vida e fadiga no Grupo Zinco. Conclusao: A
      suplementacao com zinco previne a fadiga e preserva a qualidade de vida de
      pacientes em quimioterapia para neoplasia colorretal.

PMID- 28444082
TI  - II Brazilian Consensus on the use of human immunoglobulin in patients with
      primary immunodeficiencies.
AB  - In the last few years, new primary immunodeficiencies and genetic defects have
      been described. Recently, immunoglobulin products with improved compositions and
      for subcutaneous use have become available in Brazil. In order to guide
      physicians on the use of human immunoglobulin to treat primary
      immunodeficiencies, based on a narrative literature review and their professional
      experience, the members of the Primary Immunodeficiency Group of the Brazilian
      Society of Allergy and Immunology prepared an updated document of the 1st
      Brazilian Consensus, published in 2010. The document presents new knowledge about
      the indications and efficacy of immunoglobulin therapy in primary
      immunodeficiencies, relevant production-related aspects, mode of use (routes of
      administration, pharmacokinetics, doses and intervals), adverse events (major,
      prevention, treatment and reporting), patient monitoring, presentations available
      and how to have access to this therapeutic resource in Brazil.

PMID- 28444085
TI  - Blood pressure documentation in the emergency department.
AB  - Objective: To analyze the frequency of blood pressure documentation performed by
      nursing professionals in an emergency department. Methods: This is a cross
      sectional, observational, descriptive, and analytical study, which included
      medical records of adult patients admitted to the observation ward of an
      emergency department, between March and May 2014. Data were obtained through a
      collection instrument divided into three parts: patient identification, triage
      data, and blood pressure documentation. For statistical analysis, Pearson's
      correlation coefficient was used, with a significance level of alpha<0.05.
      Results: One hundred fifty-seven records and 430 blood pressure measurements were
      analyzed with an average of three measurements per patient. Of these measures,
      46.5% were abnormal. The mean time from admission to documentation of the first
      blood pressure measurement was 2.5 minutes, with 42 minutes between subsequent
      measures. There is no correlation between the systolic blood pressure values and
      the mean time interval between blood pressure documentations: 0.173 (p=0.031).
      Conclusion: The present study found no correlation between frequency of blood
      pressure documentation and blood pressure values. The frequency of blood pressure
      documentation increased according to the severity of the patient and decreased
      during the length of stay in the emergency department.

PMID- 28444086
TI  - Performance of the dipstick screening test as a predictor of negative urine
      culture.
AB  - Objective: To investigate whether the urine dipstick screening test can be used
      to predict urine culture results. Methods: A retrospective study conducted
      between January and December 2014 based on data from 8,587 patients with a
      medical order for urine dipstick test, urine sediment analysis and urine culture.
      Sensitivity, specificity, positive and negative predictive values were determined
      and ROC curve analysis was performed. Results: The percentage of positive
      cultures was 17.5%. Nitrite had 28% sensitivity and 99% specificity, with
      positive and negative predictive values of 89% and 87%, respectively. Leukocyte
      esterase had 79% sensitivity and 84% specificity, with positive and negative
      predictive values of 51% and 95%, respectively. The combination of positive
      nitrite or positive leukocyte esterase tests had 85% sensitivity and 84%
      specificity, with positive and negative predictive values of 53% and 96%,
      respectively. Positive urinary sediment (more than ten leukocytes per microliter)
      had 92% sensitivity and 71% specificity, with positive and negative predictive
      values of 40% and 98%, respectively. The combination of nitrite positive test and
      positive urinary sediment had 82% sensitivity and 99% specificity, with positive
      and negative predictive values of 91% and 98%, respectively. The combination of
      nitrite or leukocyte esterase positive tests and positive urinary sediment had
      the highest sensitivity (94%) and specificity (84%), with positive and negative
      predictive values of 58% and 99%, respectively. Based on ROC curve analysis, the
      best indicator of positive urine culture was the combination of positives
      leukocyte esterase or nitrite tests and positive urinary sediment, followed by
      positives leukocyte and nitrite tests, positive urinary sediment alone, positive
      leukocyte esterase test alone, positive nitrite test alone and finally
      association of positives nitrite and urinary sediment (AUC: 0.845, 0.844, 0.817,
      0.814, 0.635 and 0.626, respectively). Conclusion: A negative urine culture can
      be predicted by negative dipstick test results. Therefore, this test may be a
      reliable predictor of negative urine culture. Objetivo: Verificar se a triagem de
      urina por fitas reativas e capaz de predizer a cultura de urina. Metodos Estudo
      retrospectivo realizado entre janeiro e dezembro de 2014 com 8.587 pacientes, com
      solicitacao medica de triagem de urina (fita), sedimento urinario e cultura de
      urina. Foram analisados: sensibilidade, especificidade, valor preditivo positivo,
      valor preditivo negativo e curva ROC. Resultados: Foram positivas 17,5% das
      culturas. O nitrito apresentou sensibilidade de 28% e especificidade de 99%. O
      valor preditivo positivo foi de 89% e o valor preditivo negativo de 87%. Esterase
      apresentou sensibilidade de 79% e especificidade de 84%. Valor preditivo positivo
      e valor preditivo negativo foram de 51% e 95%, respectivamente. A combinacao de
      nitrito ou esterase positivos apresentou sensibilidade de 85% e especificidade de
      84%. Valor preditivo positivo e valor preditivo negativo foram, respectivamente,
      53% e 96%. O sedimento positivo (mais de dez leucocitos por microlitro)
      apresentou sensibilidade de 92% e especificidade de 71%. O valor preditivo
      positivo foi 40% e o negativo, 98%. A combinacao de nitrito e sedimento urinario
      positivos apresentou sensibilidade de 82% e especificidade de 99%. Os valores
      preditivos positivo e negativo foram 91% e 98%, respectivamente. Para o nitrito
      ou esterase positivos mais os leucocitos positivos, a sensibilidade foi de 94% e
      a especificidade de 84%. O valor preditivo positivo foi de 58% e o negativo foi
      de 99%. Com base na curva ROC, o melhor indicador de urocultura positiva foi a
      associacao entre a esterase ou nitrito positivos na fita mais os leucocitos
      positivos no sedimento, seguido por nitrito e esterase positivos, sedimento
      urinario positivo isolado, esterase positiva isolada, nitrito positivo isolado e,
      finalmente, pela associacao entre nitrito e sedimento urinario positivos (AUC:
      0,845, 0,844, 0,817, 0,814, 0,635 e 0,626, respectivamente). Conclusao: Uma
      urocultura negativa pode ser prevista com resultados negativos na fita. Portanto,
      este teste pode ser um preditor confiavel de urocultura negativa.

PMID- 28444087
TI  - Civil liability of the ophthalmologist in the Sao Paulo Court of Appeals.
AB  - Objective: To conduct a data survey on the subject of medical claims involving
      civil liability in ophthalmology at the Sao Paulo Court of Appeals. Methods: A
      case law research was carried out on the Sao Paulo Court of Appeals website
      searching for the keyword "ophthalmologist" for all years until 2016. Results: Of
      the 65 cases found, 29 were selected. There has been an increase in the number of
      claims in ophthalmology, especially in surgical procedures on the anterior
      chamber of the eye. Most lower court judgments were for defendant. Conclusion:
      The study suggested the need for specialists to exercise the required amount of
      care when treating the patients, so that they may understand the risks inherent
      to the procedure. Despite the increase in claims, most decisions were favorable
      for the physician.

PMID- 28444088
TI  - Hypertension in patients admitted to clinical units at university hospital: post
      discharge evaluation rated by telephone.
AB  - Objective: To characterize hypertensive patients after admission to hospital
      considering the current status, compliance to treatment, habits and lifestyle,
      and knowledge and beliefs about the disease. Methods: This was an exploratory
      study with 265 hypertensive patients admitted to a medical inpatients unit of a
      university hospital. Data were collected in an interview over the telephone. The
      level of significance was set as p<0.05. Results: It was found that 32% of
      hypertensive patients had died. One hundred patients were interviewed, mean age
      of 64.15 (13.2) years, 51% were women, 56% non-white, 51% with primary education,
      52% were retired, 13% were smokers, 38% used alcohol, 80% did not perform
      physical exercise, and the mean body mass index was 35.9 (15.5) kg/m2. The
      comorbidities were heart problem (52%), diabetes (49%) and stroke (25%). As to
      antihypertensive treatment, 75% were on use, 17.3% stopped taking them and 21.3%
      missed visits. The treatment sites were the primary care unit (49%) and hospital
      (36%). As for knowledge and beliefs, 25% believed hypertension is curable, 77%
      that treatment should last for the rest of their lives, and hypertension brings
      complications (84%). A total of 46.7% were controlled. The lack of control was
      associated (p<0.05) with non-white ethnicity and absence of heart problems.
      Conclusion: There were significant deaths occurred after hospitalization and poor
      control of blood pressure, probably due to inadequate habits and lifestyles and
      non-compliance to antihypertensive treatment.

PMID- 28444089
TI  - Patient safety: knowledge between multiprofessional residents.
AB  - Objective: To assess the knowledge of multiprofesional residents in health about
      the security of the patient theme. Methods: Cross-sectional study, quantitative,
      developed with graduate courses/residence specialties of health in a public
      university of Parana, Brazil. Participants (n=78) answered a questionnaire
      containing nine objective questions related to patient safety. Data were analyzed
      using descriptive statistics, in proportion measures. The minimum 75% of correct
      answers was considered the cutoff for positive evaluation. Results: The sample
      was predominantly composed of young people from medical programs. Almost half of
      the items evaluated (n=5) achieved the established positive pattern, especially
      those who dealt with the hand hygiene moments (98.8%) and goal of the Patient
      Safety National Program (92.3%). The identification of the patient was the worst
      rated item (37.7%). In the analysis by professional areas, only the Nursing
      reached the standard of hits established. Conclusion: Knowledge of the residents
      was threshold.

PMID- 28444090
TI  - Depression and anxiety in a case series of amyotrophic lateral sclerosis:
      frequency and association with clinical features.
AB  - Objective: To investigate the frequency of anxiety and depression and their
      association with clinical features of amyotrophic lateral sclerosis. Methods:
      This is a cross-sectional and descriptive study including a consecutive series of
      patients with sporadic amyotrophic lateral sclerosis according to Awaji's
      criteria. Patients underwent clinical and psychiatric assessment (anxiety and
      depression symptoms). Results: We included 76 patients. The men/women ratio was
      1.6:1. Participants' mean age at disease onset was 55 years (SD+/-12.1). Sixty
      six patients (86.8%) were able to complete psychiatric evaluation. Clinically
      significant anxiety was found in 23 patients (34.8%) while clinically significant
      depression was found in 24 patients (36.4%). When we compared patients with and
      without depression a significant difference was seen only in the frequency of
      anxiety symptoms (p<0.001). We did further analysis comparing subgroups of
      patients classified according to the presence or not of anxiety and or
      depression, without any significant difference regarding sex, age at onset,
      initial form, disease duration or functional measures. A positive correlation
      between anxiety and depressive symptoms was found (p<0.001). Conclusion: Anxiety
      and depressive symptoms were highly correlated and frequent in patients with
      amyotrophic lateral sclerosis. In addition, anxiety and depression were not
      associated with disease duration and presentation, sex, age at onset, and
      functional score. Objetivo: Investigar a frequencia de ansiedade e depressao e
      sua associacao com aspectos clinicos da esclerose lateral amiotrofica. Metodos:
      Estudo transversal e descritivo de uma serie consecutiva de pacientes com
      esclerose lateral amiotrofica esporadica conforme os criterios de Awaji. Os
      pacientes foram submetidos a avaliacao clinica e psiquiatrica (sintomas
      depressivos e ansiosos). Resultados: Foram incluidos 76 pacientes. A relacao
      homem/mulher foi de 1,6:1. A media de idade de inicio dos sintomas foi de 55 anos
      (DP+/-12,1). Foram capazes de completar a avaliacao psiquiatrica 66 (86,8%)
      pacientes. Ansiedade clinicamente significativa foi encontrada em 23 pacientes
      (34,8%), enquanto depressao clinicamente significativa foi encontrada em 24
      pacientes (36,4%). Ao comparar os pacientes com e sem depressao, houve diferenca
      significativa apenas na frequencia de sintomas de ansiedade (p<0,001).
      Posteriormente, foram comparados subgrupos de pacientes categorizados em relacao
      a presenca ou nao de ansiedade e/ou depressao, sem diferenca significativa em
      relacao a sexo, idade de inicio dos sintomas, forma inicial, duracao da doenca ou
      na escala funcional. Foi encontrada correlacao positiva entre os sintomas de
      ansiedade e depressao (p<0,001). Conclusao: Sintomas de ansiedade e depressao sao
      frequentes em pacientes com esclerose lateral amiotrofica e estiveram altamente
      correlacionados. Ansiedade e depressao nao foram associadas com duracao da
      doenca, forma inicial, sexo, idade de inicio dos sintomas e pontuacao na escala
      funcional.

PMID- 28444091
TI  - Risk factors for mortality in ventilator-associated tracheobronchitis: a case
      control study.
AB  - Objective: To describe the microbiological characteristics and to assess the risk
      factors for mortality of ventilator-associated tracheobronchitis in a case
      control study of intensive care patients. Methods: This case-control study was
      conducted over a 6-year period in a 40-bed medical-surgical intensive care unit
      in a tertiary care, private hospital in Sao Paulo, Brazil. Case patients were
      identified using the Nosocomial Infection Control Committee database. For the
      analysis of risk factors, matched control subjects were selected from the same
      institution at a 1:8.8 ratio, between January 2006 and December 2011. Results: A
      total of 40 episodes of ventilator-associated tracheobronchitis were evaluated in
      40 patients in the intensive care unit, and 354 intensive care patients who did
      not experience tracheobronchitis were included as the Control Group. During the 6
      year study period, a total of 42 organisms were identified (polymicrobial
      infections were 5%) and 88.2% of all the microorganisms identified were Gram
      negative. Using a logistic regression model, we found the following independent
      risk factors for mortality in ventilator-associated tracheobronchitis patients:
      Acute Physiology and Chronic Health Evaluation I score (odds ratio 1.18 per unit
      of score; 95%CI: 1.05-1.38; p=0.01), and duration of mechanical ventilation (odds
      ratio 1.09 per day of mechanical ventilation; 95%CI: 1.03-1.17; p=0.004).
      Conclusion: Our study provided insight into the risk factors for mortality and
      microbiological characteristics of ventilator-associated tracheobronchitis.

PMID- 28444092
TI  - Patients with endometriosis using positive coping strategies have less
      depression, stress and pelvic pain.
AB  - Objective: To determine the correlations between coping strategies, depression,
      stress levels and pain perception in patients with endometriosis. Methods: This
      prospective and exploratory study included 171 women undergoing treatment for
      endometriosis between April and August 2014. The questionnaires used were Brief
      COPE, Beck Depression Inventory, Lipp's Stress Symptom Inventory for Adults and
      Visual Analogue Scale. Clinical data were collected from electronic medical
      records. Results: Patients with endometriosis who used positive coping strategies
      had better adaptation to stress (p<0.004) and less depression (p<0.004). The
      presence and intensity of depression, stress and acyclic pelvic pain were
      directly associated (p<0.05). The intensity of dysmenorrhea was associated with
      the degree of depression (p<0.001), whereas acyclic pelvic pain was associated
      with the degree of depression (p<0.001), stress level (p<0.001) and stress type
      (p<0.001). Conclusion: We found a positive association between coping, depression
      levels, type and levels of stress and pain intensity in patients with
      endometriosis. The use of maladaptive coping strategies focused on emotion is
      correlated with increase in depression and stress.

PMID- 28444093
TI  - Electrical stimulation attenuates morphological alterations and prevents atrophy
      of the denervated cranial tibial muscle.
AB  - Objective: To investigate if electrical stimulation through Russian current is
      able to maintain morphology of the cranial tibial muscle of experimentally
      denervated rats. Methods: Thirty-six Wistar rats were divided into four groups:
      the Initial Control Group, Final Control Group, Experimental Denervated and
      Treated Group, Experimental Denervated Group. The electrostimulation was
      performed with a protocol of Russian current applied three times per week, for 45
      days. At the end, the animals were euthanized and histological and morphometric
      analyses were performed. Data were submitted to statistical analysis with a
      significance level of p<0.05. Results: The Experimental Denervated Group and the
      Experimental Denervated and Treated Group had cross-sectional area of smaller
      fiber compared to the Final Control Group. However, there was significant
      difference between the Experimental Denervated Group and Experimental Denervated
      and Treated Group, showing that electrical stimulation minimized muscle atrophy.
      The Experimental Denervated and Treated Group and Initial Control Group showed
      similar results. Conclusion: Electrical stimulation through Russian current acted
      favorably in maintaining morphology of the cranial tibial muscle that was
      experimentally denervated, minimizing muscle atrophy. Objetivo: Investigar se a
      estimulacao eletrica pela corrente russa e capaz de manter a morfologia do
      musculo tibial cranial de ratos desnervados experimentalmente. Metodos: Foram
      utilizados 36 ratos Wistar, distribuidos em quatro grupos: Grupo Controle
      Inicial, Grupo Controle Final, Grupo Experimental Desnervado Tratado, Grupo
      Experimental Desnervado. A eletroestimulacao foi realizada com um protocolo de
      corrente russa aplicada tres vezes por semanas, durante 45 dias. Ao final, os
      animais foram eutanasiados e, em seguida, foram realizadas as analises
      histologica e morfometrica. Os dados foram submetidos a analise estatistica, com
      nivel de significancia de p<0,05. Resultados: Os Grupos Experimental Desnervado e
      o Grupo Experimental Desnervado Tratado apresentaram area de seccao transversal
      da fibra menor quando comparados ao Grupo Controle Final. Entretanto, constatou
      se diferenca significativa entre o Grupo Experimental Desnervado e o Grupo
      Experimental Desnervado Tratado, mostrando que a estimulacao eletrica minimizou
      atrofia muscular. Ainda, observou-se que o Grupo Experimental Desnervado Tratado
      apresentou resultados semelhantes ao Grupo Controle Inicial. Conclusao: A
      estimulacao eletrica por meio da corrente russa foi favoravel na manutencao da
      morfologia do musculo tibial cranial desnervado experimentalmente, minimizando a
      atrofia muscular.

PMID- 28444094
TI  - Jumping in aquatic environment after sciatic nerve compression: nociceptive
      evaluation and morphological characteristics of the soleus muscle of Wistar rats.
AB  - Objective: To evaluate the effect of jumping in aquatic environment on
      nociception and in the soleus muscle of trained and not trained Wistar rats, in
      the treatment of compressive neuropathy of the sciatic nerve. Methods: Twenty
      five Wistar rats were distributed into five groups: Control, Lesion, Trained +
      Lesion, Lesion + Exercise, and Trained + Lesion + Exercise. The training was
      jumping exercise in water environment for 20 days prior to injury, and treatment
      after the injury. Nociception was evaluated in two occasions, before injury and
      seven after injury. On the last day of the experiment, the right soleus muscles
      were collected, processed and analyzed as to morphology and morphometry. Results:
      In the assessment of nociception in the injury site, the Control Group had higher
      average than the rest, and the Lesion Group was larger than the Trained + Lesion
      and Lesion + Exercise Groups. The Control Group showed higher nociceptive
      threshold in paw, compared to the others. In the morphometric analysis, in
      relation to Control Group, all the injured groups showed decreased muscle fiber
      area, and in the Lesion Group was lower than in the Lesion + Exercise Group and
      Trained + Lesion Group. Considering the diameter of the muscle fiber, the Control
      Group had a higher average than the Trained + Lesion Group and the Trained +
      Lesion + Exercise Group; and the Lesion Group showed an average lower than the
      Trained + Lesion and Lesion + Exercise Groups. Conclusion: Resistance exercise
      produced increased nociception. When performed prior or after nerve damage, it
      proved effective in avoiding hypotrophy. The combination of the two protocols led
      to decrease in diameter and area of the muscle fiber. Objetivo: Avaliar os
      efeitos do salto em meio aquatico, na nocicepcao e no musculo soleo, em ratos
      Wistar treinados e nao treinados, no tratamento de neuropatia compressiva do
      nervo isquiatico. Metodos: Foram distribuidos em cinco grupos 25 ratos Wistar:
      Controle, Lesao, Treinado + Lesao, Lesao + Exercicio e Treinado + Lesao +
      Exercicio. O treino foi com exercicio de salto em meio aquatico durante 20 dias,
      previo a lesao, e o tratamento ocorreu apos a lesao. Foram realizadas avaliacoes
      da nocicepcao, sendo uma pre-lesao e sete pos-lesao. No ultimo dia de
      experimento, os musculos soleos direitos foram coletados, processados e
      analisados por meio de morfologia e morfometria. Resultados: Na avaliacao da
      nocicepcao no local da lesao, o Grupo Controle apresentou media maior que os
      demais, e o Grupo Lesao foi maior que os Grupos Treinado + Lesao e Lesao +
      Exercicio. O Grupo Controle apresentou limiar nociceptivo na pata maior com
      relacao aos demais. Nas analises morfometricas, em relacao ao Grupo Controle,
      todos os grupos lesionados apresentaram diminuicao da area da fibra muscular; o
      Grupo Lesao apresentou-se menor que os Grupos Treinado + Lesao e Lesao +
      Exercicio. No diametro da fibra muscular, o Grupo Controle apresentou media maior
      que os Grupos Treinado + Lesao e Treinado + Lesao + Exercicio, e o Grupo Lesao
      apresentou media menor que os Grupos Treinado + Lesao e Lesao + Exercicio.
      Conclusao: O exercicio fisico resistido produziu aumento da nocicepcao. Quando
      realizado previamente ou apos a lesao nervosa, mostrou-se eficaz em evitar a
      hipotrofia. A associacao dos dois protocolos levou a diminuicao do diametro e da
      area da fibra muscular.

PMID- 28444096
TI  - Off-label use of rhBMP-2 as bone regeneration strategies in mandibular
      ameloblastoma unicystic.
AB  - Jawbone reconstruction after tumor resection is one of the most challenging
      clinical tasks for maxillofacial surgeons. Osteogenic, osteoinductive,
      osteoconductive and non-antigenic properties of autogenous bone place this bone
      as the gold standard for solving problems of bone availability. However, the need
      for a second surgical site to harvest the bone graft increases significantly both
      the cost and the morbidity associated with the reconstructive procedures. Bone
      grafting gained an important tool with the discovery of bone morphogenetic
      proteins in 1960. Benefit of obtaining functional and real bone matrix without
      need of second surgical site seems to be the great advantage of use bone
      morphogenetic proteins. This study analyzed the use of rhBMP-2 in unicystic
      ameloblastoma of the mandible, detailing its structure, mechanisms of cell
      signaling and biological efficacy, in addition to present possible advantages and
      disadvantages of clinical use of rhBMP-2 as bone regeneration strategy. RESUMO A
      reconstrucao ossea dos maxilares apos resseccoes tumorais e uma das tarefas mais
      dificeis para o cirurgiao maxilofacial. As propriedades osteogenicas,
      osteoindutoras, osteocondutoras e nao antigenicas do osso autogeno o colocam como
      o padrao-ouro para a solucao de problemas de disponibilidade ossea. Entretanto a
      coleta do enxerto osseo necessita de um segundo sitio cirurgico, aumentando
      significativamente o custo e a morbidade associados ao procedimento
      reconstrutivo. A enxertia ossea ganhou uma excelente ferramenta com a descoberta
      das proteinas osseas morfogeneticas na decada de 1960. O beneficio da obtencao de
      matriz ossea verdadeira e funcional, sem a necessidade de um segundo sitio
      cirurgico, parece ser a grande vantagem do uso das proteinas osseas
      morfogeneticas. Neste contexto, o objetivo deste estudo foi analisar a utilizacao
      da rhBMP-2 na regeneracao ossea de ameloblastoma mandibular unicistico,
      detalhando sua estrutura, seus mecanismos de sinalizacao celular e sua eficacia
      biologica, alem de apresentar potenciais vantagens e desvantagens da utilizacao
      clinica das rhBMP-2, enquanto estrategia regenerativa.

PMID- 28444095
TI  - Judicial demand of medications through the Federal Justice of the State of
      Parana.
AB  - Objective: To describe the profile of lawsuits related to drug requests filled at
      the Federal Justice of the State of Parana. Methods: A cross-sectional study, and
      the data were obtained through consulting the lawsuits at the online system of
      the Federal Justice of Parana. Results: Out of 347 lawsuits included in the
      study, 55% of plaintiffs were women, with a median age of 56 years. Oncology was
      the field with more requests (23.6%), and the highest mean costs. A wide variety
      of diseases and broad variety of requested drugs were found in the lawsuits.
      Approximately two-thirds of them were requested by the brand name, and the most
      often requested drugs were palivizumab and tiotropium bromide. Only 14.5% of the
      requested medicines were registered in the National Medication Register. The
      Public Defender's Office filled actions in 89.6% of cases and all lawsuits had an
      interim relief. The mean time for approval was 35 days and 70% of requests were
      granted. Conclusion: Oncology was the field with the highest demand for medicines
      at the Federal Justice of Parana in 2014. A great variety of medications was
      requested. The Public Defender's Office represented most lawsuits. All demands
      had an interim relief, and the majority of requests were granted, within an
      average of 35 days. Objetivo: Descrever o perfil das acoes que solicitam
      medicamentos ajuizadas na Justica Federal do Parana. Metodos: Estudo transversal
      descritivo, cujos dados foram obtidos por meio de consulta aos processos no
      sistema on-line da Justica Federal do Parana. Resultados: Dentre os 347 processos
      incluidos no estudo, 55% dos autores eram mulheres, com mediana da idade de 56
      anos, sendo a area mais procurada a oncologia (23,6%). A area oncologica tambem
      foi a que apresentou maiores custos medios. Foi ampla a variedade de doencas
      geradoras das acoes e tambem foi consequentemente grande a variedade de
      medicamentos solicitados. Cerca de dois tercos dos farmacos foram solicitados
      pelo nome comercial, e os mais requeridos foram o palivizumabe e brometo de
      tiotropio. Apenas 14,5% dos medicamentos solicitados estavam cadastrados no
      Registro Nacional de Medicamentos. A Defensoria Publica impetrou as acoes em
      89,6% dos casos. Todos os processos pediam antecipacao de tutela do medicamento.
      O tempo medio para deferimento foi de 35 dias, sendo que 70% dos pedidos foram
      deferidos. Conclusao: A area com maior numero de casos de demanda de medicamentos
      na Justica Federal do Parana no ano de 2014 foi de Oncologia. Observou-se grande
      variedade de medicamentos solicitados. A maioria das acoes foi impetrada pela
      Defensoria Publica. Todas as demandas exigiram antecipacao de tutela, sendo que a
      maioria dos pedidos foram deferidos, num prazo medio de 35 dias.

PMID- 28444097
TI  - Chronic polyarthritis as the first manifestation of childhood systemic
      polyarteritis nodosa.
AB  - Arthritis has been reported as an acute pattern, generally evanescent with
      oligoarthritis, mostly affecting knees and ankles in childhood systemic
      polyarteritis nodosa. However, chronic polyarthritis with morning stiffness
      mimicking juvenile idiopathic arthritis has not been reported. We describe the
      case of a 4-year old girl who had additive and chronic polyarthritis with edema,
      tenderness, pain on motion and morning stiffness for 2 months. After 45 days, she
      also presented painful subcutaneous nodules and erythematous-violaceous lesions
      in the extensor region of upper and lower limbs. She was admitted to university
      hospital due to high fever, malaise, myalgia, anorexia, loss of weight (1kg),
      painful skin lesions and severe functional disability. She was bedridden by
      chronic polyarthritis with limitation on motion. Systolic and diastolic blood
      pressures were greater than 95th percentile for height. Urine protein/creatinine
      ratio was 0.39g/day, and immunological tests were negative. Anti-streptolysin O
      was 1,687UI/mL. Skin biopsy revealed necrotizing vasculitis in medium- and small
      sized vessels compatible with polyarteritis nodosa. Therefore, we had the
      diagnosis of systemic polyarteritis nodosa. Prednisone 2mg/kg/day was
      administered with complete resolution of skin lesions and arthritis, and
      improvement of proteinuria (0.26g/day) after 15 days. The diagnosis of childhood
      systemic polyarteritis nodosa should be considered for patients with chronic
      polyarthritis associated to cutaneous vasculitis triggered by streptococcal
      infection. RESUMO Na poliarterite nodosa sistemica pediatrica, a artrite
      caracteriza-se pelo padrao agudo, geralmente evanescente, com oligoartrite, e
      afeta principalmente joelhos e tornozelos. No entanto, a poliartrite cronica com
      rigidez matinal e simulando artrite idiopatica juvenil ainda nao foi relatada.
      Descrevemos o caso de uma menina de 4 anos que apresentou poliartrite cronica
      aditiva com edema, dor a palpacao e movimento, e rigidez matinal por 2 meses.
      Apos 45 dias, tambem apresentou nodulos subcutaneos dolorosos e lesoes eritemato
      violaceas na regiao extensora dos membros superiores e inferiores. Foi internada
      no hospital universitario por conta de febre alta, mal-estar, mialgia, anorexia,
      perda de peso (1kg), lesoes de pele muito dolorosas e incapacidade funcional
      grave. Estava restrita ao leito devido a poliartrite cronica com limitacao do
      movimento. Pressoes sistolica e diastolica foram maiores que percentil 95 para
      altura. Relacao proteina/creatinina urinaria estava 0,39g/dia, e os testes
      imunologicos foram negativos. Antiestreptolisina O era 1.687UI/mL. A biopsia de
      pele revelou vasculite necrosante de vasos de pequeno e medio calibre, compativel
      com poliarterite nodosa. Portanto, foi realizado o diagnostico de poliarterite
      nodosa sistemica. Foi administrada prednisona 2mg/kg/dia com resolucao completa
      das lesoes de pele e da artrite, alem de melhora da proteinuria (0,26g/dia) apos
      15 dias. O diagnostico de poliarterite nodosa sistemica pediatrica deve ser
      considerado em pacientes com poliartrite cronica associado a lesoes cutaneas
      vasculiticas, sendo a infeccao estreptococica um importante fator desencadeante.

PMID- 28444098
TI  - The cerebrospinal fluid in multiple sclerosis: far beyond the bands.
AB  - The cerebrospinal fluid analysis has been employed for supporting multiple
      sclerosis diagnosis and ruling out the differential diagnoses. The most classical
      findings reflect the inflammatory nature of the disease, including mild
      pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G,
      and, most typically, the presence of oligoclonal bands. In recent years, new
      biomarkers have emerged in the context of multiple sclerosis. The search for new
      biomarkers reflect the need of a better evaluation of disease activity, disease
      progression, and treatment efficiency. A more refined evaluation of disease and
      therapy status can contribute to better therapeutic choices, particularly in
      escalation of therapies. This is very relevant taking into account the
      availability of a greater number of drugs for multiple sclerosis treatment in
      recent years. In this review, we critically evaluate the current literature
      regarding the most important cerebrospinal fluid biomarkers in multiple
      sclerosis. The determination of biomarkers levels, such as chemokine ligand 13,
      fetuin A, and mainly light neurofilament has shown promising results in the
      evaluation of this disease, providing information that along with clinical and
      neuroimaging data may contribute to better therapeutic decisions. RESUMO A
      analise do liquido cefalorraquidiano tem sido empregada para avaliacao
      diagnostica da esclerose multipla e a exclusao dos diagnosticos diferenciais. Os
      achados classicos refletem a natureza inflamatoria da doenca, incluindo discreta
      pleocitose, leve hiperproteinorraquia, aumento da sintese intratecal de
      imunoglobulina G e, mais tipicamente, a presenca de bandas oligoclonais. Nos
      ultimos anos, surgiram novos biomarcadores para esclerose multipla, e esta busca
      por marcadores reflete a necessidade de melhor avaliar a atividade e a progressao
      da doenca, bem como a eficacia terapeutica. Uma avaliacao mais refinada da
      atividade da doenca e da resposta aos medicamentos pode contribuir para melhores
      decisoes terapeuticas, particularmente no que se refere a troca de medicacao.
      Isto e muito importante nos dias de hoje, quando surgem novas opcoes
      medicamentosas. Neste artigo de revisao, avaliamos criticamente a literatura
      atual referente aos novos marcadores liquoricos na esclerose multipla. A
      mensuracao destes marcadores, como a quimiocina CXCL13, fetuina A e,
      principalmente, o neurofilamento de cadeia leve, demonstrou resultados
      promissores na avaliacao da doenca, provendo informacoes que, em conjunto com
      dados clinicos e de neuroimagem, podem contribuir para melhores decisoes
      terapeuticas.

PMID- 28444100
TI  - An unexpected cause of gastric submucosal lesion.

PMID- 28444099
TI  - Association of the protein tyrosine phosphatase non-receptor 22 polymorphism
      (PTPN22) with endometriosis: a meta-analysis.
AB  - Objective: To evaluate PTPN22 C1858T polymorphism and the risk of endometriosis.
      Methods: A meta-analysis of 10 published case-control studies (from four
      articles), with a total sample of 971 cases and 1,181 controls, was performed. We
      estimated risk (odds ratio and 95% confidence intervals) of endometriosis
      associations with the C1858T polymorphism. Results: A significant increased risk
      in all genetic models of the variant T allele with endometriosis (odds ratio:
      3.14-5.55; p<0.00001-0.002) was found. The analysis without the study whose
      controls deviated from the Hardy-Weinberg equilibrium exacerbated these effects
      in the homozygous and recessive models (odds ratio: 7.19-9.45; p<0.00001-0.0002).
      In the Italian subgroup, a significant risk association was found in the
      homozygous and recessive models (odds ratio: 8.72-11.12; p=0.002). Conclusion:
      The associations observed between PTPN22 (C1858T) and the risk of endometriosis
      suggest this polymorphism might be a useful susceptibility marker for this
      disease. Objetivo: Avaliar o polimorfismo PTPN22 C1858T e o risco de
      endometriose. Metodos: Foi realizada uma metanalise de 10 estudos caso-controle
      publicados (a partir de quatro artigos), com uma amostra total de 971 casos e
      1.181 controles. O risco da associacao da endometriose com o polimorfismo C1858T
      foi estimado em razao de chance e intervalo de confianca de 95%. Resultados:
      Observou-se um aumento de risco significativo em todos os modelos geneticos com o
      alelo variante T e a endometriose (razao de chance: 3,14-5,55; p<0,00001-0,002).
      A analise sem incluir o estudo, em que os controles nao estavam em equilibrio de
      Hardy-Weinberg, mostrou aumento significativo nos modelos homozigotos e
      recessivos (razao de chance: 7,19-9,45; p<0,00001-0,0002). No subgrupo italiano,
      uma associacao significativa foi encontrada considerando os modelos homozigoto e
      recessivo (razao de chance: 8,72-11,12; p=0,002). Conclusao: As associacoes
      observadas entre PTPN22 (C1858T) e o risco de endometriose sugerem que este
      polimorfismo pode ser um marcador de suscetibilidade para a endometriose.

PMID- 28444101
TI  - Cauda equina syndrome caused by filum terminale lipoma: magnetic resonance
      imaging features and surgical treatment.

PMID- 28444102
TI  - PET/MRI: a novel hybrid imaging technique. Major clinical indications and
      preliminary experience in Brazil.
AB  - In recent years, medical imaging with hybrid techniques has widely accepted and
      employed in clinical routine. PET/MRI offers significant advantages, including
      excellent contrast and resolution and reduced ionizing radiation, as compared to
      well-established PET/CT. Therefore, PET/MRI is a promising modality for oncologic
      imaging of some regions, such as brain, head and neck, liver and pelvis. This
      article set out to analyze clinical conditions that could benefit from PET/MRI
      imaging based on our caseload. The potential of PET/MRI to become the imaging
      modality of choice for assessment of neurologic and oncologic conditions
      associated with soft tissues is highlighted. Clinical aspects of PET/MRI and its
      application to clinical cases are illustrated with examples extracted from the
      authors' preliminary experience. RESUMO Nos ultimos anos, imagens medicas com
      tecnologias hibridas tornaram-se amplamente aceitas e utilizadas na pratica
      clinica. O PET/RM possui vantagens importantes, incluindo excelentes contrastes e
      resolucao, e menor radiacao ionizante, em comparacao ao PET/TC. Por isto, e uma
      modalidade promissora para exames de imagem de pacientes oncologicos, para
      avaliar o cerebro, cabeca e pescoco, o figado e a pelve. O objetivo deste artigo
      foi analisar as situacoes clinicas que se beneficiariam de exames de PET/RM a
      partir de uma casuistica. Destacamos o potencial desta tecnica se tornar o metodo
      de imagem de escolha para doencas neurologicas e oncologicas que envolvam partes
      moles. Os aspectos clinicos de PET/RM e sua aplicacao aos casos clinicos sao
      ilustrados com exemplos da experiencia inicial dos autores.

PMID- 28444103
TI  - Precision Medicine.

PMID- 28444104
TI  - Psychomotor Ability and Short-term Memory, and Reading and Mathematics
      Achievement in Children.
AB  - Objective: The aim of our study was to examine whether the findings from previous
      research, indicating the role of short-term memory as a mediator of the
      relationship between motor coordination and academic achievement in adolescents,
      is also evident in a younger child population. Method: The study utilized a
      quantative cross-sectional design involving 133 children aged 8-12. The McCarron
      Assessment of Neuromuscular Development (MAND) provided four indicators of
      psychomotor ability (Finger Nose, Walking, Balancing, and Jumping). The Woodcock
      Johnson Cognitive battery and the Automated Working Memory Assessment (AWMA)
      provided two measures of short-term memory (Numbers Reversed and Digit Recall)
      and the WJIII Achievement battery provided two measures of reading achievement
      (Letter-word Identification and Passage Comprehension) and two measures of
      mathematics achievement (Applied Problems and Calculation). Structural equation
      modeling was used, controlling for age, processing speed, crystallized, and fluid
      intelligence where appropriate. Results: The results found support for the
      hypothesis that short-term memory fully mediates the relationship between
      psychomotor ability and reading and mathematics achievement. Conclusion: These
      findings indicate the significant affect of psychomotor ability on learning
      outcomes and consequently the need to assess these in considering learning
      difficulties, and as such these findings also advance understanding of
      developmental neural mechanisms underpinning the relationships.

PMID- 28444105
TI  - Clinical, pathological, and demographic factors associated with development of
      recurrences after surgical resection in elderly patients with neuroendocrine
      tumors.
AB  - Background: Incidence of locoregional neuroendocrine tumors (NETs) is rising.
      However, after curative resection, the patterns and risk factors associated with
      recurrence remain unknown. Consensus guidelines recommend surveillance every 6-12
      months for up to 10 years after surgery for resected, well-differentiated NETs
      irrespective of patient demographics, site, grade or stage of tumor with few
      exceptions. Patients and methods: From the Surveillance, Epidemiology, and End
      Results (SEER)-Medicare database, we identified localized and regional stage NET
      patients who underwent surgical resection between January 2002 and December 2011.
      Development of recurrence was identified by capturing at least two claims
      indicative of metastatic disease until 31 December 2013. Results: Of the 2366
      identified patients (median age 73 years), 369 (16%) developed metastatic disease
      within 5 years and only an additional 1% developed metastases between years 5 and
      10 with the majority dying due to unrelated causes. The 5-year risk of developing
      metastases (hazard ratio, HR) varied significantly (log-rank P < 0.001) by grade:
      9.9% versus 25.9% (2.2) versus 48.1% (4.4) for grades 1, 2, and  >= 3,
      respectively; stage: 10.3% versus 31.1% (2.8) for localized versus regional;
      primary tumor size: 7.6% versus 15% (1.3) versus 26.6% (1.5) for <1, 1-2, and > 2
      cm, respectively; and site: ranging from 11.3% for colon to 23.9% for pancreas.
      Conclusions: Contrary to current guidelines, our study suggests that surveillance
      recommendations should be tailored according to patient and tumor
      characteristics. Surveillance past 5 years may be avoided in elderly patients
      with competing morbidities or low risk of recurrence. Pancreatic, lung, higher
      grade, and regional NETs have a higher risk of recurrence and may be considered
      for future adjuvant trials.

PMID- 28444106
TI  - The Association of Air Pollution With Pubertal Development: Evidence From Hong
      Kong's "Children of 1997" Birth Cohort.
AB  - Many pollutants are endocrine disruptors with impacts on reproduction and health
      in animals, but evidence in humans, of which sex-specific effects on pubertal
      development may be an indicator, is less clear. We examined the association of
      air pollution in utero and during early life with pubertal development in Hong
      Kong, China, an area with a high level of air pollution compared with other
      similarly developed cities. We assessed sex-specific associations of particulate
      matter less than or equal to 10 MUm in diameter (PM10), nitric oxide, sulfur
      dioxide, and nitrogen dioxide in different growth phases with clinically assessed
      pubertal stage at approximately age 11 years (as indicated by Tanner stage) in a
      large population-representative birth cohort, the "Children of 1997." We used
      partial least squares regression to account for colinearity between air
      pollutants. Among 1,938 girls, PM10 exposure in utero and during infancy was
      negatively associated with pubertal stage and breast development, whereas among
      2,136 boys, sulfur dioxide and nitrogen dioxide exposure in utero, during
      infancy, and in childhood were negatively associated with pubertal stage. These
      sex-specific associations with pubertal development are consistent with endocrine
      disrupting effects. Given the health impact of altered pubertal timing, further
      investigation across the life course may help quantify the full effects and the
      corresponding need for preventive measures.

PMID- 28444107
TI  - Apelin-13 inhibits lipoprotein lipase expression via the APJ/PKCalpha/miR-361-5p
      signaling pathway in THP-1 macrophage-derived foam cells.
AB  - Atherosclerotic lesions are characterized by the accumulation of abundant lipids
      and chronic inflammation. Previous researches have indicated that macrophage
      derived lipoprotein lipase (LPL) promotes atherosclerosis progression by
      accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although
      apelin-13 has been regarded as an atheroprotective factor, it remains unclear
      whether it can regulate the expression of LPL. The aim of this study was to
      explore the effects of apelin-13 on the expression of LPL and the underlying
      mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly
      decreased cellular levels of total cholesterol, free cholesterol, and cholesterol
      ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that
      treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as
      interleukin-6 (IL-6), interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNF-alpha). It was also found that apelin-13 inhibited the expression of
      LPL as revealed by western blot and real-time PCR analyses. Bioinformatics
      analyses and dual-luciferase reporter assay indicated that miR-361-5p directly
      downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition,
      apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in
      cells. Finally, we demonstrated that apelin-13 downregulated the expression of
      LPL through activating the activity of PKCalpha. Taken together, our results
      showed that apelin-13 downregulated the expression of LPL via activating the
      APJ/PKCalpha/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells,
      leading to inhibition of lipid accumulation and pro-inflammatory cytokine
      secretion. Therefore, our studies provide important new insight into the
      inhibition of lipid accumulation and pro-inflammatory cytokine secretion by
      apelin-13, and highlight apelin-13 as a promising therapeutic target in
      atherosclerosis.

PMID- 28444109
TI  - Temporal Changes in Mortality Related to Extreme Temperatures for 15 Cities in
      Northeast Asia: Adaptation to Heat and Maladaptation to Cold.
AB  - Understanding how the temperature-mortality association worldwide changes over
      time is crucial to addressing questions of human adaptation under climate change.
      Previous studies investigated the temporal changes in the association over a few
      discrete time frames or assumed a linear change. Also, most studies focused on
      attenuation of heat-related mortality and studied the United States or Europe.
      This research examined continuous temporal changes (potentially nonlinear) in
      mortality related to extreme temperature (both heat and cold) for 15 cities in
      Northeast Asia (1972-2009). We used a generalized linear model with splines to
      simultaneously capture 2 types of nonlinearity: nonlinear association between
      temperature and mortality and nonlinear change over time in the association. We
      combined city-specific results to generate country-specific results using
      Bayesian hierarchical modeling. Cold-related mortality remained roughly constant
      over decades and slightly increased in the late 2000s, with a larger increase for
      cardiorespiratory deaths than for deaths from other causes. Heat-related
      mortality rates have decreased continuously over time, with more substantial
      decrease in earlier decades, for older populations and for cardiorespiratory
      deaths. Our findings suggest that future assessment of health effects of climate
      change should account for the continuous changes in temperature-related health
      risk and variations by factors such as age, cause of death, and location.

PMID- 28444108
TI  - Racial/Ethnic Differences in Left Ventricular Structure and Function in Chronic
      Kidney Disease: The Chronic Renal Insufficiency Cohort.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of
      cardiovascular disease (CVD) and it is especially common among Blacks. Left
      ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but
      there are limited data on racial variation in left ventricular structure and
      function among persons with CKD. METHODS: In a cross-sectional analysis of the
      Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different
      types of left ventricular remodeling (concentric hypertrophy, eccentric
      hypertrophy, and concentric remodeling) by race/ethnicity. We used multinomial
      logistic regression to test whether race/ethnicity associated with different
      types of left ventricular remodeling independently of potential confounding
      factors. RESULTS: We identified 1,164 non-Hispanic Black and 1,155 non-Hispanic
      White participants who completed Year 1 visits with echocardiograms that had
      sufficient data to categorize left ventricular geometry type. Compared to non
      Hispanic Whites, non-Hispanic Blacks had higher mean left ventricular mass index
      (54.7 +/- 14.6 vs. 47.4 +/- 12.2 g/m2.7; P < 0.0001) and prevalence of concentric
      LVH (45.8% vs. 24.9%). In addition to higher systolic blood pressure and
      treatment with >3 antihypertensive medications, Black race/ethnicity was
      independently associated with higher odds of concentric LVH compared to White
      race/ethnicity (odds ratio: 2.73; 95% confidence interval: 2.02, 3.69).
      CONCLUSION: In a large, diverse cohort with CKD, we found significant differences
      in left ventricular mass and hypertrophic morphology between non-Hispanic Blacks
      and Whites. Future studies will evaluate whether higher prevalence of LVH
      contribute to racial/ethnic disparities in cardiovascular outcomes among CKD
      patients.

PMID- 28444110
TI  - The association of orthostatic hypotension with falls-an end to the debate?

PMID- 28444111
TI  - Pattern recognition receptors: immune targets to enhance cancer immunotherapy.
AB  - Durable tumor responses and significant levels of disease control rates have been
      described in more than 20 advanced/metastatic cancer types with B7-family immune
      checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies.
      These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab
      and atezolizumab are currently revolutionizing the way we envision the future of
      cancer care. However these clinical benefits are not observed in all cancer types
      and in every patient. Therefore, our clinical challenge is to identify
      therapeutic strategies which could overcome the primary and secondary resistances
      to these novel cancer immunotherapies. Pattern recognition receptors (PRRs) are
      other critical costimulatory molecules of immune cells, notably myeloid cells
      (macrophages and dendritic cells). They were initially described as sensors for
      'danger signals' released by pathogens (e.g. viral DNA and bacterial proteins).
      We know now that PRRs can also be recruited and activated upon recognition of
      endogenous stress signals such as molecules released upon self-cell death (e.g.
      ATP and HMGB1). Natural endo/exogenous or synthetic PRRs agonists have notably
      the ability to activate phagocytosis and antigen presentation by myeloid cells
      residing in the tumor micro-environment. In pre-clinical models, these PRRs
      agonists have also been shown to overcome the resistance to T-cell targeted
      immune checkpoints anti-CTLA-4 and anti-PD-1/PD-L1. This manuscript reviews the
      current knowledge on this major family of immune receptors and the molecules
      targeting them which are currently in clinical development.

PMID- 28444113
TI  - Prenatal Exposure to Fever and Infections and Academic Performance: A Multilevel
      Analysis.
AB  - Prenatal exposure to fever and infections has been linked to various
      neurodevelopmental disorders, but it is not yet known whether more subtle effects
      on neurodevelopment may exist as well. Therefore, we aimed to investigate whether
      these early-life exposures were associated with academic performance in childhood
      and early adolescence. Children and mothers who were enrolled in the Danish
      National Birth Cohort during 1996-2002 were included in this study. Information
      on fever and infections common in pregnancy was prospectively collected in 2
      pregnancy interviews and linked with assessments of academic performance from the
      2010-2013 Danish National Tests. Hierarchical multilevel linear regression of
      216,350 assessments made in 71,850 children born to 67,528 mothers revealed no
      differences in academic performance among the children according to prenatal
      exposure to fever (odds ratio (OR) = 1.01, 95% confidence interval (CI): 1.00,
      1.03), any infection (OR = 1.00, 95% CI: 0.99, 1.01), genitourinary infection (OR
      = 1.01, 95% CI: 0.99, 1.02), prolonged cough (OR = 1.00, 95% CI: 0.99, 1.02), or
      diarrhea (OR = 0.99, 95% CI: 0.97, 1.00). The findings were supported in
      different types of academic assessments, with different timings of exposure, and
      in sibling comparisons. This large population-based study suggested that prenatal
      exposure to fever and common infections does not affect the child's basic school
      performance.

PMID- 28444112
TI  - Incidence, course, and management of toxicities associated with cobimetinib in
      combination with vemurafenib in the coBRIM study.
AB  - Background: In the coBRIM phase III trial, the addition of cobimetinib, an MEK
      inhibitor, to vemurafenib, a BRAF inhibitor, significantly improved progression
      free survival [hazard ratio (HR), 0.58; P < 0.0001] and overall survival (HR,
      0.70; P = 0.005) in advanced BRAF-mutated melanoma. Here, we report on the
      incidence, course, and management of key adverse events (AEs) in the coBRIM
      study. Patients and methods: Patients were randomly assigned 1:1 to receive
      vemurafenib (960 mg twice a day) and either cobimetinib (60 mg once a day, 21
      days on/7 days off) or placebo. In addition to standard safety evaluations,
      patients underwent regular ophthalmic, cardiac, and dermatologic surveillance
      examinations. Results: Of 495 patients recruited to the study, 493 patients
      received treatment and constituted the safety population (cobimetinib combined
      with vemurafenib, 247; vemurafenib, 246). At data cut-off (30 September 2015),
      median follow-up was 18.5 months. Nearly every patient experienced an AE. In
      patients who received cobimetinib combined with vemurafenib, the frequency of
      grade >=3 AEs was higher than in patients who received vemurafenib alone (75%
      versus 61%). Most AEs, including grade >=3 AEs, occurred within the first
      treatment cycle. After the first cycle (28 days), the incidence of common AEs
      (rash, diarrhoea, photosensitivity, elevated creatine phosphokinase, serous
      retinopathy, pyrexia, and liver laboratory abnormalities) decreased substantially
      over time. Most AEs were managed conservatively by supportive care measures, dose
      modifications of study treatment, and, occasionally, permanent treatment
      discontinuation. Conclusions: These data indicate that most AEs arising from
      treatment with cobimetinib combined with vemurafenib generally occur early in the
      treatment course, are mild or moderate and are manageable by patient monitoring,
      dose modification and supportive care. ClinicalTrials.gov: NCT01689519.

PMID- 28444114
TI  - Efficacy of everolimus plus octreotide LAR in patients with advanced
      neuroendocrine tumor and carcinoid syndrome: final overall survival from the
      randomized, placebo-controlled phase 3 RADIANT-2 study.
AB  - Background: In the phase 3 RADIANT-2 study, everolimus plus octreotide long
      acting repeatable (LAR) showed improvement of 5.1 months in median progression
      free survival versus placebo plus octreotide LAR among patients with advanced
      neuroendocrine tumors associated with carcinoid syndrome. The progression-free
      survival P-value was marginally above the prespecified threshold for statistical
      significance. Here, we report final overall survival (OS) and key safety update
      from RADIANT-2. Patients and methods: The RADIANT-2 trial compared everolimus (10
      mg/day, orally; n = 216) versus placebo (n = 213), both in conjunction with
      octreotide LAR (30 mg, intramuscularly, every 28 days). Patients, unblinded at
      the time of progression or after end of double-blind core phase following primary
      analysis, were offered open-label everolimus with octreotide LAR (open-label
      phase). In the open-label phase, patients had similar safety and efficacy
      assessments as those in the core phase. For OS, hazard ratios (HRs) with 95% CIs
      using unadjusted Cox model and a Cox model adjusted for prespecified baseline
      covariates were calculated. Results: A total of 170 patients received open-label
      everolimus (143 crossed over from the placebo arm; 27 in the everolimus arm
      continued to receive the same treatment after unblinding). The median OS (95% CI)
      after 271 events was 29.2 months (23.8-35.9) for the everolimus arm and 35.2
      months (30.0-44.7) for the placebo arm (HR, 1.17; 95% CI, 0.92-1.49). HR adjusted
      for baseline covariates was 1.08 (95% CI, 0.84-1.38). The most frequent drug
      related grade 3 or 4 AEs reported during the open-label phase were diarrhea
      (5.3%), fatigue (4.7%), and stomatitis (4.1%). Deaths related to pulmonary or
      cardiac failure were observed more frequently in the everolimus arm. Conclusion:
      No significant difference in OS was observed for the everolimus plus octreotide
      LAR and placebo plus octreotide LAR arms of the RADIANT-2 study, even after
      adjusting for imbalances in the baseline covariates. Clinical Trial Number:
      NCT00412061, www.clinicaltrials.gov.

PMID- 28444115
TI  - Assessing treatment efficacy in the subset of responders in a randomized clinical
      trial.
AB  - Background: Durability of response is a clinically relevant dimension of the
      treatment effect in randomized clinical trials; it is often measured by comparing
      among the responders the duration of response between the treatment arms.
      However, since the comparison groups are defined by response (a post
      randomization event), it is subject to analysis-by-responder bias, especially if
      the proportion of responders differs between the arms. Methods: Two simple
      methods are developed that use tumor shrinkage measurements in order to lessen
      analysis-by-responder bias by generating more comparable patient subsets in the
      control and experimental arms of the trial. These subsets are then used to
      estimate between-arm differences in response duration. In the subtraction method,
      responding patients with the least tumor shrinkage in the treatment arm with more
      responders are removed from the patient subset for that arm. In the addition
      method, non-responding patients with the most tumor shrinkage in the treatment
      arm with fewer responders are added to the patient subset for that arm. In both
      methods, the numbers of patients subtracted or added are such that the proportion
      of patients in the modified patient subset is the same as the proportion of
      responders in the other treatment arm. Results: The methods are demonstrated on a
      hypothetical dataset where they are shown to eliminate analysis-by-responder
      bias, and on two published analyses of randomized trials that compared the
      duration of response between the treatment arms. Conclusions: The proposed
      methods can lessen the analysis-by-responder bias. These methods to compare
      duration of response between treatment arms may provide a useful exploratory
      analysis to measure treatment efficacy among responders.

PMID- 28444116
TI  - Effectiveness of in-hospital geriatric co-management: a systematic review and
      meta-analysis.
AB  - Background: geriatric consultation teams have failed to impact clinical outcomes
      prompting geriatric co-management programmes to emerge as a promising strategy to
      manage frail patients on non-geriatric wards. Objective: to conduct a systematic
      review of the effectiveness of in-hospital geriatric co-management. Data sources:
      MEDLINE, EMBASE, CINAHL and CENTRAL were searched from inception to 6 May 2016.
      Reference lists, trial registers and PubMed Central Citations were additionally
      searched. Study selection: randomised controlled trials and quasi-experimental
      studies of in-hospital patients included in a geriatric co-management study. Two
      investigators performed the selection process independently. Data extraction:
      standardised data extraction and assessment of risk of bias were performed
      independently by two investigators. Results: twelve studies and 3,590 patients
      were included from six randomised and six quasi-experimental studies. Geriatric
      co-management improved functional status and reduced the number of patients with
      complications in three of the four studies, but studies had a high risk of bias
      and outcomes were measured heterogeneously and could not be pooled. Co-management
      reduced the length of stay (pooled mean difference, -1.88 days [95% CI, -2.44 to 
      1.33]; 11 studies) and may reduce in-hospital mortality (pooled odds ratio, 0.72
      [95% CI, 0.50-1.03]; 7 studies). Meta-analysis identified no effect on the number
      of patients discharged home (5 studies), post-discharge mortality (3 studies) and
      readmission rate (4 studies). Conclusions: there was low-quality evidence of a
      reduced length of stay and a reduced number of patients with complications, and
      very low-quality evidence of better functional status as a result of geriatric co
      management.

PMID- 28444117
TI  - Exposure Opportunity: The Advantages of Including Men in Analyses of Female
      Related Risk Factors.
AB  - Intuitively, researchers do not include subjects who do not have the opportunity
      to be exposed, such as men in studies on oral contraceptives (OCs). We aimed to
      explore in which situations it is nevertheless beneficial to do so. We considered
      the effect of including men in case-control analyses of 8 different hypothetical
      data sets on the effect of OC use and venous thrombosis. In all scenarios, OC use
      was the exposure of interest, sex the factor that determined exposure
      opportunity, and air travel another risk factor. In some of these scenarios, sex
      and air travel were included as confounders or effect modifiers. Logistic
      regression was used to estimate odds ratios. Standard errors of the estimated log
      odds ratios, including and excluding men, were compared. We also studied the
      effect of including men using data from 1999-2004 from a case-control study on
      risk factors for venous thrombosis, conducted in the Netherlands. In all
      hypothetical examples, and in the real-data study, addition of men to the
      analysis yielded the same odds ratios when correctly adjusting for confounding.
      Moreover, use of additional subjects often led to more precise estimates. We
      suggest that subjects who do not have the opportunity to be exposed should not
      routinely be excluded from epidemiologic studies.

PMID- 28444118
TI  - Development and evaluation of the medication-based index of physical function
      (MedIP).
AB  - Background: the development of an objective and comprehensive drug-based index of
      physical function for older adults has the potential to more accurately predict
      fall risk. Design: the index was developed using 862 adults (ages 57-85) from the
      National Social Life, Health, and Aging Project (NSHAP) Wave 1 study. The index
      was evaluated in 70 adults (ages 51-88) from a rehabilitation study of dizziness
      and balance. Methods: the prevalence among 601 drugs for 1,694 side effects was
      used with fall history to determine the magnitude of each side effect's
      contribution towards physical function. This information was used to calculate a
      Medication-based Index of Physical function (MedIP) score for each individual
      based on his or her medication profile. The MedIP was compared to the timed up
      and go (TUG) test as well as drug counts using receiver operating characteristic
      (ROC) analysis. The associations between various indices of physical function and
      MedIP were calculated. Results: within the NSHAP data set, the MedIP was better
      than drug counts or TUG at predicting falls based on ROC analysis. Using scores
      above and below the cutpoint, the MedIP was a significant predictor of falls (OR
      = 2.61 [95% CI 1.83, 3.64]; P < 0.001). Using an external data set, it was shown
      that the MedIP was significantly correlated with fall number (P = 0.044),
      composite physical function (P = 0.026) and preferred gait speed (P = 0.043).
      Conclusion: the MedIP has the potential to become a useful tool in the healthcare
      and fall prevention of older individuals.

PMID- 28444119
TI  - Spatial Variability in ADHD-Related Behaviors Among Children Born to Mothers
      Residing Near the New Bedford Harbor Superfund Site.
AB  - Attention-deficit/hyperactivity disorder (ADHD) has an uncertain etiology, with
      potential contributions from different risk factors such as prenatal
      environmental exposure to organochlorines and metals, social risk factors, and
      genetics. The degree to which geographic variability in ADHD is independent of,
      or explained by, risk factors may provide etiological insight. We investigated
      determinants of geographic variation in ADHD-related behaviors among children
      living near the polychlorinated biphenyl-contaminated New Bedford Harbor (NBH)
      Superfund site in Massachusetts. Participants were 573 children recruited at
      birth (1993-1998) who were born to mothers residing near the NBH site. We
      assessed ADHD-related behaviors at age 8 years using Conners' Teacher Rating
      Scale-Revised: Long Version. Adjusted generalized additive models were used to
      smooth the association of pregnancy residence with ADHD-related behaviors and
      assess whether prenatal organochlorine or metal exposures, sociodemographic
      factors, or other factors explained spatial patterns. Models that adjusted for
      child's age and sex displayed significantly increased ADHD-related behavior among
      children whose mothers resided west of the NBH site during pregnancy. These
      spatial patterns persisted after adjusting for prenatal exposure to
      organochlorines and metals but were no longer significant after controlling for
      sociodemographic factors. The findings underscore the value of spatial analysis
      in identifying high-risk subpopulations and evaluating candidate risk factors.

PMID- 28444121
TI  - Dynamic laser speckle analyzed considering inhomogeneities in the biological
      sample.
AB  - Dynamic laser speckle phenomenon allows a contactless and nondestructive way to
      monitor biological changes that are quantified by second-order statistics applied
      in the images in time using a secondary matrix known as time history of the
      speckle pattern (THSP). To avoid being time consuming, the traditional way to
      build the THSP restricts the data to a line or column. Our hypothesis is that the
      spatial restriction of the information could compromise the results, particularly
      when undesirable and unexpected optical inhomogeneities occur, such as in cell
      culture media. It tested a spatial random approach to collect the points to form
      a THSP. Cells in a culture medium and in drying paint, representing homogeneous
      samples in different levels, were tested, and a comparison with the traditional
      method was carried out. An alternative random selection based on a Gaussian
      distribution around a desired position was also presented. The results showed
      that the traditional protocol presented higher variation than the outcomes using
      the random method. The higher the inhomogeneity of the activity map, the higher
      the efficiency of the proposed method using random points. The Gaussian
      distribution proved to be useful when there was a well-defined area to monitor.

PMID- 28444120
TI  - Premenopausal Hysterectomy and Risk of Ovarian Cancer in African-American Women.
AB  - Although the inverse association between hysterectomy and epithelial ovarian
      cancer (EOC) was considered well established, investigators in recent studies
      including women diagnosed after 2000 have observed modest increases in risk. Most
      studies have been conducted in white women with little representation of African
      American women. We examined the relationship between premenopausal hysterectomy
      and EOC in African-American women and explored whether hormone therapy (HT)
      modified this association in 614 cases and 743 controls enrolled in the African
      American Cancer Epidemiology Study (2010-2015). Premenopausal hysterectomy was
      inversely associated with the odds of EOC (odds ratio (OR) = 0.75, 95% confidence
      interval (CI): 0.56, 1.01). Qualitative interaction by estrogen-only HT was
      present; among never users of estrogen-only HT, premenopausal hysterectomy was
      associated with a significantly decreased odds of EOC (OR = 0.65, 95% CI: 0.46,
      0.92), whereas among users of estrogen-only HT, a positive association was
      observed (OR = 1.71, 95% CI: 0.76, 3.84). In a population of African-American
      women diagnosed after 2000, our overall results are consistent with the inverse
      association observed in the era before 2000, yet the effect modification by HT
      suggests that HT use among women who have had hysterectomies may negate the
      protective effects of hysterectomy on EOC, creating the appearance of a null or
      slightly increased risk.

PMID- 28444122
TI  - Acute hospital admission of the frail older person: an opportunity to discuss
      future care.

PMID- 28444123
TI  - A Comparison of Four Computerized Neurocognitive Assessment Tools to a
      Traditional Neuropsychological Test Battery in Service Members with and without
      Mild Traumatic Brain Injury.
AB  - Objective: Computerized neurocognitive assessment tools (NCATS) are often used as
      a screening tool to identify cognitive deficits after mild traumatic brain injury
      (mTBI). However, differing methodology across studies renders it difficult to
      identify a consensus regarding the validity of NCATs. Thus, studies where
      multiple NCATs are administered in the same sample using the same methodology are
      warranted. Method: We investigated the validity of four NCATs: the ANAM4, CNS-VS,
      CogState, and ImPACT. Two NCATs were randomly assigned and a battery of
      traditional neuropsychological (NP) tests administered to healthy control active
      duty service members (n = 272) and to service members within 7 days of an mTBI (n
      = 231). Analyses included correlations between NCAT and the NP test scores to
      investigate convergent and discriminant validity, and regression analyses to
      identify the unique variance in NCAT and NP scores attributed to group status.
      Effect sizes (Cohen's f2) were calculated to guide interpretation of data.
      Results: Only 37 (0.6%) of the 5,655 correlations calculated between NCATs and NP
      tests are large (i.e. r >= 0.50). The majority of correlations are small (i.e.
      0.30 > r >= 0.10), with no clear patterns suggestive of convergent or
      discriminant validity between the NCATs and NP tests. Though there are
      statistically significant group differences across most NCAT and NP test scores,
      the unique variance accounted for by group status is minimal (i.e. semipartial R2
      <= 0.033, 0.024, 0.062, and 0.011 for ANAM4, CNS-VS, CogState, and ImPACT,
      respectively), with effect sizes indicating small to no meaningful effect.
      Conclusion: Though the results are not overly promising for the validity of the
      four NCATs we investigated, traditional methods of investigating psychometric
      properties may not be appropriate for computerized tests. We offer several
      conceptual and methodological considerations for future studies regarding the
      validity of NCATs.

PMID- 28444125
TI  - Sudden cardiac death.
AB  - Introduction: Sudden cardiac arrest continues to be the leading cause of death in
      the industrialized world. Sources of data: Original papers, reviews and
      guidelines. Areas of agreement: Community programs for lay bystander
      cardiopulmonary resuscitation (CPR) and automatic external defibrillation improve
      outcomes. Post-arrest care, including targeted temperature management (TTM)
      combined with early coronary angiography and percutaneous coronary intervention,
      is helpful for those suffering cardiac arrest during an ST-segment elevation
      myocardial infarction. Areas of controversy: (1) The optimal approach to
      encourage lay bystanders to assist with resuscitation efforts. (2) Whether TTM
      combined with early coronary angiography is cost effective for those without ST
      elevation on their post-arrest ECG is unknown. Growing points: Increasing data
      show that chest compression-only CPR is preferred by lay rescuers and improves
      local survival rates. Areas timely for developing research: Randomized clinical
      trials are underway to examine the utility of early coronary angiography in the
      treatment of post-arrest patients without ST-segment elevation.

PMID- 28444124
TI  - Predicting discharge to institutional long-term care following acute
      hospitalisation: a systematic review and meta-analysis.
AB  - Background: moving into long-term institutional care is a significant life event
      for any individual. Predictors of institutional care admission from community
      dwellers and people with dementia have been described, but those from the acute
      hospital setting have not been systematically reviewed. Our aim was to establish
      predictive factors for discharge to institutional care following acute
      hospitalisation. Methods: we registered and conducted a systematic review
      (PROSPERO: CRD42015023497). We searched MEDLINE; EMBASE and CINAHL Plus in
      September 2015. We included observational studies of patients admitted directly
      to long-term institutional care following acute hospitalisation where factors
      associated with institutionalisation were reported. Results: from 9,176 records,
      we included 23 studies (n = 354,985 participants). Studies were heterogeneous,
      with the proportions discharged to a care home 3-77% (median 15%). Eleven studies
      (n = 12,642), of moderate to low quality, were included in the quantitative
      synthesis. The need for institutional long-term care was associated with age
      (pooled odds ratio (OR) 1.02, 95% confidence intervals (CI): 1.00-1.04), female
      sex (pooled OR 1.41, 95% CI: 1.03-1.92), dementia (pooled OR 2.14, 95% CI: 1.24
      3.70) and functional dependency (pooled OR 2.06, 95% CI: 1.58-2.69). Conclusions:
      discharge to long-term institutional care following acute hospitalisation is
      common, but current data do not allow prediction of who will make this
      transition. Potentially important predictors evaluated in community cohorts have
      not been examined in hospitalised cohorts. Understanding these predictors could
      help identify individuals at risk early in their admission, and support them in
      this transition or potentially intervene to reduce their risk.

PMID- 28444126
TI  - CImbinator: a web-based tool for drug synergy analysis in small- and large-scale
      datasets.
AB  - Motivation: Drug synergies are sought to identify combinations of drugs
      particularly beneficial. User-friendly software solutions that can assist
      analysis of large-scale datasets are required. Results: CImbinator is a web
      service that can aid in batch-wise and in-depth analyzes of data from small-scale
      and large-scale drug combination screens. CImbinator offers to quantify drug
      combination effects, using both the commonly employed median effect equation, as
      well as advanced experimental mathematical models describing dose response
      relationships. Availability and Implementation: CImbinator is written in Ruby and
      R. It uses the R package drc for advanced drug response modeling. CImbinator is
      available at http://cimbinator.bioinfo.cnio.es , the source-code is open and
      available at https://github.com/Rbbt-Workflows/combination_index . A Docker image
      is also available at https://hub.docker.com/r/mikisvaz/rbbt-ci_mbinator/ .
      Contact: asmund.flobak@ntnu.no or miguel.vazquez@cnio.es. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28444127
TI  - HLA class I binding prediction via convolutional neural networks.
AB  - Motivation: Many biological processes are governed by protein-ligand
      interactions. One such example is the recognition of self and non-self cells by
      the immune system. This immune response process is regulated by the major
      histocompatibility complex (MHC) protein which is encoded by the human leukocyte
      antigen (HLA) complex. Understanding the binding potential between MHC and
      peptides can lead to the design of more potent, peptide-based vaccines and
      immunotherapies for infectious autoimmune diseases. Results: We apply machine
      learning techniques from the natural language processing (NLP) domain to address
      the task of MHC-peptide binding prediction. More specifically, we introduce a new
      distributed representation of amino acids, name HLA-Vec, that can be used for a
      variety of downstream proteomic machine learning tasks. We then propose a deep
      convolutional neural network architecture, name HLA-CNN, for the task of HLA
      class I-peptide binding prediction. Experimental results show combining the new
      distributed representation with our HLA-CNN architecture achieves state-of-the
      art results in the majority of the latest two Immune Epitope Database (IEDB)
      weekly automated benchmark datasets. We further apply our model to predict
      binding on the human genome and identify 15 genes with potential for self
      binding. Availability and Implementation: Codes to generate the HLA-Vec and HLA
      CNN are publicly available at: https://github.com/uci-cbcl/HLA-bind . Contact:
      xhx@ics.uci.edu. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 28444128
TI  - Low-dose ionizing radiation induces therapeutic neovascularization in a pre
      clinical model of hindlimb ischemia.
AB  - Aims: We have previously shown that low-dose ionizing radiation (LDIR) induces
      angiogenesis but there is no evidence that it induces neovascularization in the
      setting of peripheral arterial disease. Here, we investigated the use of LDIR as
      an innovative and non-invasive strategy to stimulate therapeutic
      neovascularization using a model of experimentally induced hindlimb ischemia
      (HLI). Methods and results: After surgical induction of unilateral HLI, both
      hindlimbs of female C57BL/6 mice were sham-irradiated or irradiated with four
      daily fractions of 0.3 Gy, in consecutive days and allowed to recover. We
      demonstrate that LDIR, significantly improved blood perfusion in the murine
      ischemic limb by stimulating neovascularization, as assessed by laser Doppler
      flow, capillary density, and collateral vessel formation. LDIR significantly
      increased the circulating levels of VEGF, PlGF, and G-CSF, as well as the number
      of circulating endothelial progenitor cells (EPCs) mediating their incorporation
      to ischemic muscles. These effects were dependent upon LDIR exposition on the
      ischemic niche (thigh and shank regions). In irradiated ischemic muscles, these
      effects were independent of the recruitment of monocytes and macrophages.
      Importantly, LDIR induced a durable and simultaneous up-regulation of a
      repertoire of pro-angiogenic factors and their receptors in endothelial cells
      (ECs), as evident in ECs isolated from the irradiated gastrocnemius muscles by
      laser capture microdissection. This specific mechanism was mediated via vascular
      endothelial growth factor (VEGF) receptor signaling, since VEGF receptor
      inhibition abrogated the LDIR-mediated gene up-regulation and impeded the
      increase in capillary density. Finally, the vasculature in an irradiated non
      ischemic bed was not affected and after 52 week of LDIR exposure no differences
      in the incidence of morbidity and mortality were seen. Conclusions: These
      findings disclose an innovative, non-invasive strategy to induce therapeutic
      neovascularization in a mouse model of HLI, emerging as a novel approach in the
      treatment of critical limb ischemia patients.

PMID- 28444129
TI  - Return to sport following stress fractures of the great toe sesamoids: a
      systematic review.
AB  - Introduction: This review aims to provide information on return rates and times
      to sport following stress fractures of the great toe sesamoids (SFGTSs). Sources
      of data: A systematic search of CINAHAL, Cochrane, EMBASE, Google Scholar,
      Medline, PEDro, Scopus, SPORTDiscus and Web of Science was performed using the
      keywords 'stress', 'fractures', 'great', 'toe', 'sesamoid', 'athletes', 'sports',
      'non-operative', 'conservative', 'operative' and 'return to sport'. Areas of
      agreement: Fourteen studies were included: three studies reported on the outcome
      of conservatively-managed SFGTSs; thirteen studies reported on the outcome of
      surgically-managed SFGTSs. The management principles were to attempt conservative
      management for 2-6 months using activity modification, analgesia, orthotics and
      physiotherapy; if symptoms persisted following this, surgical management was to
      be recommended, either with internal fixation or sesamoidectomy. Areas of
      controversy: The optimal treatment modalities for SFGTSs remain to be defined.
      Growing points: Internal fixation shows the best return to full-level sport rates
      with low rates of complications. Areas timely for developing research: Future
      prospective studies should aim to establish the optimal treatment modalities for
      SFGTSs.

PMID- 28444130
TI  - Clinically Relevant Cut-off Points for the Diagnosis of Sarcopenia in Older
      Korean People.
AB  - Background: The optimal criteria applied to older Korean people have not been
      defined. We aimed to define clinically relevant cut-off points for older Korean
      people and to compare the predictive validity with other definitions of
      sarcopenia. Methods: Nine hundred and sixteen older Koreans (>=65 years) were
      included in this cross-sectional observational study. We used conditional
      inference tree analysis to determine cut-off points for height-adjusted grip
      strength (GS) and appendicular skeletal muscle mass (ASM), for use in the
      diagnosis of sarcopenia. We then compared the Korean sarcopenia criteria with the
      Foundation for the National Institutes of Health and Asian Working Group for
      Sarcopenia criteria, using frailty, assessed with the Korean Frailty Index, as an
      outcome variable. Results: For men, a residual GS (GSre) of <= 0.25 was defined
      as weak, and a residual ASM (ASMre) of <= 1.29 was defined as low. Corresponding
      cut-off points for women were a GSre of <= 0.17 and an ASMre of <= 0.69. GSre and
      ASMre values were adjusted for height. In logistic regression analysis with new
      cut-off points, the adjusted odds ratios for pre-frail or frail status in the
      sarcopenia group were 3.23 (95% confidence interval [CI] 1.33-7.83) for the men
      and 1.74 (95% CI 0.91-3.35) for the women. In receiver operating characteristic
      curve analysis, the unadjusted area under the curve for Korean sarcopenia
      criteria in men and women were 0.653 and 0.608, respectively (p < .001).
      Conclusions: Our proposed cut-off points for low GS and low ASM should be useful
      in the diagnosis of sarcopenia in older Korean people.

PMID- 28444131
TI  - Fulvestrant plus LHRH analogues in male with synchronous breast and prostate
      cancer.

PMID- 28444132
TI  - Tyrosine phosphorylation of eNOS regulates myocardial survival after an ischaemic
      insult: role of PYK2.
AB  - Aims: Endothelial nitric oxide (NO) synthase (eNOS) is known to play a
      cardioprotective protective. However, the molecular mechanisms regulating eNOS
      activity during ischaemia/reperfusion (I/R) injury are incompletely understood.
      eNOS is a substrate for several kinases that positively or negatively affect its
      enzymatic activity. Herein, we sought to correlate eNOS phosphorylation status
      with cardiomyocyte survival and we investigated the contribution of the proline
      rich tyrosine kinase 2 (PYK2)/eNOS axis to the regulation of myocardial infarct
      size in vivo. Methods and results: Exposure of H9c2 cardiomyocytes to H2O2 lead
      to PYK2 phosphorylation on its activator site (Y402) and eNOS phosphorylation on
      the inhibitor site Y656 and the activator site S1176. Both H2O2-induced eNOS
      phosphorylation events were abolished by PYK2 pharmacological inhibition or gene
      knockdown. Activity assays demonstrated that phosphorylation of the tyrosine
      inhibitory site exerts a dominant effect over S1176. In cardiomyocytes subjected
      to oxidative stress or oxygen-glucose deprivation, inhibition of PYK2 limited
      cell injury; this effect was prevented by inhibition of NO production. In vivo,
      ischaemia-reperfusion induced an early activation of PYK2, leading to eNOS
      phosphorylation on Y656, which, in turn, reduced NO output, as judged by the low
      tissue levels of its downstream effector cGMP. Moreover, pharmacological blockade
      of PYK2 alleviated eNOS inhibition and prevented cardiac damage following I/R
      injury in wild-type, but not in eNOS KO mice. Conclusion: The current studies
      demonstrate that PYK2 is a pivotal regulator of eNOS function in myocardial
      infarction and identify PYK2 as a novel therapeutic target for cardioprotection.

PMID- 28444133
TI  - Increased collagen within the transverse tubules in human heart failure.
AB  - Aims: In heart failure transverse-tubule (t-tubule) remodelling disrupts calcium
      release, and contraction. T-tubules in human failing hearts exhibit increased
      labelling by wheat germ agglutinin (WGA), a lectin that binds to the dystrophin
      associated glycoprotein complex. We hypothesized changes in this complex may
      explain the increased WGA labelling and contribute to t-tubule remodelling in the
      failing human heart. In this study we sought to identify the molecules
      responsible for this increased WGA labelling. Methods and results: Confocal and
      super-resolution fluorescence microscopy and proteomic analyses were used to
      quantify left ventricle samples from healthy donors and patients with idiopathic
      dilated cardiomyopathy (IDCM). Confocal microscopy demonstrated both WGA and
      dystrophin were located at t-tubules. Super-resolution microscopy revealed that
      WGA labelling of t-tubules is largely located within the lumen while dystrophin
      was restricted to near the sarcolemma. Western blots probed with WGA reveal a 5.7
      fold increase in a 140 kDa band in IDCM. Mass spectrometry identified this band
      as type VI collagen (Col-VI) comprised of alpha1(VI), alpha2(VI), and alpha3(VI)
      chains. Pertinently, mutations in Col-VI cause muscular dystrophy. Western
      blotting identified a 2.4-fold increased expression and 3.2-fold increased WGA
      binding of Col-VI in IDCM. Confocal images showed that Col-VI is located in the t
      tubules and that their diameter increased in the IDCM samples. Super-resolution
      imaging revealed Col-VI was restricted to the t-tubule lumen where increases were
      associated with displacement in the sarcolemma as identified from dystrophin
      labelling. Samples were also labelled for type I, III, and IV collagen. Both
      confocal and super-resolution imaging identified that these collagens were also
      present within t-tubule lumen. Conclusion: Increased expression and labelling of
      collagen in IDCM samples indicates fibrosis may contribute to t-tubule
      remodelling in human heart failure.

PMID- 28444134
TI  - Characterization of FOXO1, 3 and 4 transcription factors in ovaries of fetal,
      prepubertal and adult rhesus macaques.
AB  - The phosphoinositide 3-kinase/AKT (protein kinase B) signaling pathway negatively
      regulates follicle activation via the forkhead box O (FOXO) transcription factor
      in rodents. FOXO3 knockout mice exhibit global activation of primordial follicles
      leading to early depletion of ovarian follicles and subsequent infertility.
      Whether a similar mechanism for follicle activation exists in the primate ovary
      is unclear. In the current study, protein localization of FOXO1, 3, and 4 as well
      as their upstream regulator, AKT/p-AKT, was examined in rhesus macaque ovaries of
      three developmental stages: fetal, prepubertal, and adult. FOXO1 protein is
      expressed in granulosa cells of fetal, prepubertal, and adult ovaries. FOXO3 is
      distributed sparsely in the mitotically active germ cells, but its expression
      decreases following follicle formation in the macaque fetal ovary. In addition,
      FOXO3 is seldom with interanimal variation in the prepubertal ovary and is absent
      in the adult ovary. FOXO4 is nondetectable in fetal ovaries, although it is
      expressed in some theca cells of antral follicles and some stromal cells in
      prepubertal and adult ovaries. Our results suggest that the regulation and/or
      function of FOXO3 in the primate primordial follicle may differ than that of the
      rodent. Nevertheless, AKT/p-AKT is expressed in macaque primordial oocytes,
      suggesting that similar upstream events but different downstream effects may
      regulate primordial follicle activation in nonhuman primates compared to rodents.
      Elucidation of the mechanism responsible for follicle activation in primates will
      be crucial for understanding primary ovarian insufficiency, improving female
      fertility, and applying techniques for in vitro maturation of follicles for
      fertility preservation in cancer survivors.

PMID- 28444135
TI  - Prevalence and Correlates of Olfactory Dysfunction in Old Age: A Population-Based
      Study.
AB  - Background: Olfactory dysfunction (OD) in old age is associated with poor health
      outcomes. Interrelationships among different correlates of OD can offer insights
      into the underlying mechanisms, but to date remain understudied. Methods: Odor
      identification performance and self-reported olfactory functioning were studied
      in 2,234 people aged 60-90 years, who were free of neurodegenerative disease and
      enrolled in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K)
      study, Stockholm, Sweden. OD was defined as the inability to identify more than
      10 out of 16 odors (free or cued identification) in a standardized odor
      identification task. OD prevalence was estimated, and associations with
      demographic, genetic, vascular, clinical, and behavioral factors, as well as
      their interactions were examined using multiple logistic regression analyses.
      Results: Overall prevalence of OD was 24.8% (CI: 23.1; 26.6). Self-reports were
      characterized by low sensitivity (35%), but high specificity (87%). Advancing age
      (OR = 15.50, CI = 9.40; 26.10 between the first and last age group), and history
      of coronary heart disease (OR = 1.35, 95% CI = 1.04; 1.75) were the principal
      factors associated with an increased probability of OD, whereas female gender (OR
      = 0.53, 95% CI = 0.43; 0.66) and more years of education (OR = 0.97, CI 0.94;
      0.99) were linked to a lower probability. Exploratory interaction analyses
      indicated that prevalence of OD was particularly elevated among Apolipropotein E
      (APOE) epsilon4 allele carriers who were also obese, and that being physically
      active counteracted the negative impact of cerebrovascular disease on OD.
      Conclusion: Demographic and genetic factors, but also prior and current health
      insults, are linked to OD in old age. Modulatory effects of behavioral factors
      highlight their value as possible prevention targets.

PMID- 28444136
TI  - Asymmetrical natural hybridization varies among hybrid swarms between two diploid
      Rhododendron species.
AB  - Background and Aims: The extent to which hybridization leads to gene flow between
      plant species depends on the structure of hybrid populations. However, if this
      varies between locations, species barriers might prove permeable in some
      locations but not in others. To assess possible variation in hybrid population
      structure, the magnitude and direction of natural hybridization between two
      Chinese endemic species, Rhododendron spiciferum and Rhododendron spinuliferum ,
      were evaluated. Methods: Thirteen nuclear microsatellite markers were employed to
      characterize 566 individuals collected from 15 non-allopatric populations and
      nine allopatric parental populations. Chloroplast DNA (cpDNA) sequences were
      obtained from a subset of samples. Genetic structure and direction of gene flow
      was determined using a combination of STRUCTURE and NEWHYBRIDS analysis. Key
      Results: Nuclear analysis revealed that parental taxa formed two genetically
      distinct clusters and hybrids shared the genetic background of both parents and
      did not form a separate genetic lineage. Overall, hybrid swarms were dominated by
      early- and later-generation hybrids, with a significantly higher proportion of
      hybrids (59.6 %) possessing >50 % R. spiciferum-like nuclear germplasm. The cpDNA
      analysis further indicated that a significantly greater proportion of hybrids
      (61.1 %) possessed the R. spiciferum cpDNA haplotype. Conclusions: Gene flow
      between R. spiciferum and R. spinuliferum was found to be bidirectional in 14 of
      the 15 hybrid swarms and asymmetrical in six hybrid swarms. Asymmetrical gene
      flow was evident for only nuclear DNA (nDNA) in two populations, for only cpDNA
      in three populations, and for both nDNA and cpDNA in one population.
      Collectively, the variation in genetic structure found among the 15 hybrid swarms
      suggests that introgression rather than hybrid speciation is a more likely
      outcome of hybridization between these hybridizing taxa.

PMID- 28444137
TI  - Effects of Serotonin Transporter Gene Variation on Impulsivity Mediated by
      Default Mode Network: A Family Study of Depression.
AB  - Serotonergic neurotransmission, potentially through effects on the brain's
      default mode network (DMN), may regulate aspects of attention including impulse
      control. Indeed, genetic variants of the serotonin transporter (5-HTT) have been
      implicated in impulsivity and related psychopathology. Yet it remains unclear the
      mechanism by which the 5-HTT genetic variants contribute to individual
      variability in impulse control. Here, we tested whether DMN connectivity mediates
      an association between the 5-HTT genetic variants and impulsivity. Participants
      (N = 92) were from a family cohort study of depression in which we have
      previously shown a broad distribution of 5-HTT variants. We genotyped for 5
      HTTLPR and rs25531 (stratified by transcriptional efficiency: 8 low/low, 53
      low/high, and 31 high/high), estimated DMN structural connectivity using
      diffusion probabilistic tractography, and assessed behavioral measures of
      impulsivity (from 12 low/low, 48 low/high, and 31 high/high) using the Continuous
      Performance Task. We found that low transcriptional efficiency genotypes were
      associated with decreased connection strength between the posterior DMN and the
      superior frontal gyrus (SFG). Path modeling demonstrated that decreased DMN-SFG
      connectivity mediated the association between low-efficiency genotypes and
      increased impulsivity. Taken together, this study suggests a gene-brain-behavior
      pathway that perhaps underlies the role of the serotonergic neuromodulation in
      impulse control.

PMID- 28444138
TI  - The evolution of neuropeptide signalling: insights from echinoderms.
AB  - Neuropeptides are evolutionarily ancient mediators of neuronal signalling that
      regulate a wide range of physiological processes and behaviours in animals.
      Neuropeptide signalling has been investigated extensively in vertebrates and
      protostomian invertebrates, which include the ecdysozoans Drosophila melanogaster
      (Phylum Arthropoda) and Caenorhabditis elegans (Phylum Nematoda). However, until
      recently, an understanding of evolutionary relationships between neuropeptide
      signalling systems in vertebrates and protostomes has been impaired by a lack of
      genome/transcriptome sequence data from non-ecdysozoan invertebrates. The
      echinoderms-a deuterostomian phylum that includes sea urchins, sea cucumbers and
      starfish-have been particularly important in providing new insights into
      neuropeptide evolution. Sequencing of the genome of the sea urchin
      Strongylocentrotus purpuratus (Class Echinoidea) enabled discovery of (i) the
      first invertebrate thyrotropin-releasing hormone-type precursor, (ii) the first
      deuterostomian pedal peptide/orcokinin-type precursors and (iii) NG peptides-the
      'missing link' between neuropeptide S in tetrapod vertebrates and crustacean
      cardioactive peptide in protostomes. More recently, sequencing of the neural
      transcriptome of the starfish Asterias rubens (Class Asteroidea) enabled
      identification of 40 neuropeptide precursors, including the first kisspeptin and
      melanin-concentrating hormone-type precursors to be identified outside of the
      chordates. Furthermore, the characterization of a corazonin-type neuropeptide
      signalling system in A. rubens has provided important new insights into the
      evolution of gonadotropin-releasing hormone-related neuropeptides. Looking
      forward, the discovery of multiple neuropeptide signalling systems in echinoderms
      provides opportunities to investigate how these systems are used to regulate
      physiological and behavioural processes in the unique context of a decentralized,
      pentaradial bauplan.

PMID- 28444140
TI  - Restitution slope is determined by the steady state action potential duration:
      law and disorder.

PMID- 28444139
TI  - Multi-label classifier based on histogram of gradients for predicting the
      anatomical therapeutic chemical class/classes of a given compound.
AB  - Motivation: Given an unknown compound, is it possible to predict its Anatomical
      Therapeutic Chemical class/classes? This is a challenging yet important problem
      since such a prediction could be used to deduce not only a compound's possible
      active ingredients but also its therapeutic, pharmacological and chemical
      properties, thereby substantially expediting the pace of drug development. The
      problem is challenging because some drugs and compounds belong to two or more ATC
      classes, making machine learning extremely difficult. Results: In this article a
      multi-label classifier system is proposed that incorporates information about a
      compound's chemical-chemical interaction and its structural and fingerprint
      similarities to other compounds belonging to the different ATC classes. The
      proposed system reshapes a 1D feature vector to obtain a 2D matrix representation
      of the compound. This matrix is then described by a histogram of gradients that
      is fed into a Multi-Label Learning with Label-Specific Features classifier.
      Rigorous cross-validations demonstrate the superior prediction quality of this
      method compared with other state-of-the-art approaches developed for this
      problem, a superiority that is reflected particularly in the absolute true rate,
      the most important and harshest metric for assessing multi-label systems.
      Availability and implementation: The MATLAB code for replicating the experiments
      presented in this article is available at
      https://www.dropbox.com/s/7v1mey48tl9bfgz/ToolPaperATC.rar?dl=0 . Contact:
      loris.nanni@unipd.it. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 28444141
TI  - Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis.
AB  - A biomarker that will enable the identification of patients at high-risk for
      developing post-injury epilepsy is critically required. Microvascular pathology
      and related blood-brain barrier dysfunction and neuroinflammation were shown to
      be associated with epileptogenesis after injury. Here we used prospective,
      longitudinal magnetic resonance imaging to quantitatively follow blood-brain
      barrier pathology in rats following status epilepticus, late electrocorticography
      to identify epileptic animals and post-mortem immunohistochemistry to confirm
      blood-brain barrier dysfunction and neuroinflammation. Finally, to test the
      pharmacodynamic relevance of the proposed biomarker, two anti-epileptogenic
      interventions were used; isoflurane anaesthesia and losartan. Our results show
      that early blood-brain barrier pathology in the piriform network is a sensitive
      and specific predictor (area under the curve of 0.96, P < 0.0001) for epilepsy,
      while diffused pathology is associated with a lower risk. Early treatments with
      either isoflurane anaesthesia or losartan prevented early microvascular damage
      and late epilepsy. We suggest quantitative assessment of blood-brain barrier
      pathology as a clinically relevant predictive, diagnostic and pharmaco!dynamics
      biomarker for acquired epilepsy.

PMID- 28444143
TI  - Reply to Ozaras et al.

PMID- 28444142
TI  - Regulatory states in the developmental control of gene expression.
AB  - A growing body of evidence shows that gene expression in multicellular organisms
      is controlled by the combinatorial function of multiple transcription factors.
      This indicates that not the individual transcription factors or signaling
      molecules, but the combination of expressed regulatory molecules, the regulatory
      state, should be viewed as the functional unit in gene regulation. Here, I
      discuss the concept of the regulatory state and its proposed role in the genome
      wide control of gene expression. Recent analyses of regulatory gene expression in
      sea urchin embryos have been instrumental for solving the genomic control of cell
      fate specification in this system. Some of the approaches that were used to
      determine the expression of regulatory states during sea urchin embryogenesis are
      reviewed. Significant developmental changes in regulatory state expression
      leading to the distinct specification of cell fates are regulated by gene
      regulatory network circuits. How these regulatory state transitions are encoded
      in the genome is illuminated using the sea urchin endoderm-mesoderms cell fate
      decision circuit as an example. These observations highlight the importance of
      considering developmental gene regulation, and the function of individual
      transcription factors, in the context of regulatory states.

PMID- 28444144
TI  - Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.
AB  - We report 2 fatal cases of congenital Zika virus (ZIKV) infection. Brain
      anomalies, including atrophy of the cerebral cortex and brainstem, and cerebellar
      aplasia were observed. The spinal cord showed architectural distortion, severe
      neuronal loss, and microcalcifications. The ZIKV proteins and flavivirus-like
      particles were detected in cytoplasm of spinal neurons, and spinal cord samples
      were positive for ZIKV RNA.

PMID- 28444145
TI  - Parental Separation and Cardiometabolic Risk Factors in Late Adolescence: A Cross
      Cohort Comparison.
AB  - The aim of this study was to explore the association between parental separation
      during childhood (up to 18 years of age) and cardiometabolic risk factors (body
      mass index, fat mass index, blood pressure, physical activity, smoking, and
      alcohol consumption) in late adolescence using a cross-cohort comparison and to
      explore whether associations differ according to the age at which the parental
      separation occurred and the presence or absence of parental conflict prior to
      separation. Data from the Avon Longitudinal Study of Parents and Children
      (ALSPAC, United Kingdom) (1991-2011) and the 1993 Pelotas Birth Cohort (Brazil)
      (1993-2011) were used. The associations of parental separation with children's
      cardiometabolic risk factors were largely null. Higher odds of daily smoking were
      observed in both cohorts for those adolescents whose parents separated (for
      ALSPAC, odds ratio = 1.46; for Pelotas Birth Cohort, odds ratio = 1.98). Some
      additional associations were observed in the Pelotas Birth Cohort but were
      generally in the opposite direction to our a priori hypothesis: Parental
      separation was associated with lower blood pressure and fat mass index, and with
      more physical activity. No consistent differences were observed when analyses
      were stratified by child's age at parental separation or parental conflict.

PMID- 28444146
TI  - Nonsense in the testis: multiple roles for nonsense-mediated decay revealed in
      male reproduction.
AB  - Nonsense-mediated mRNA decay, or NMD, is a quality control mechanism that
      identifies cytoplasmic mRNAs containing translational termination (stop) codons
      in specific contexts-either premature termination codons or unusually long 3?
      untranslated regions (UTRs)-and targets them for degradation. In recent studies,
      researchers in different labs have knocked out important genes involved in NMD,
      the up-frameshift genes Upf2 and Upf3a, and one component of chromatoid bodies,
      the Tudor domain-containing protein Tdrd6, and examined the consequences for
      spermatogenesis. Disruption of Upf2 during early stages of spermatogenesis
      resulted in disappearance of nearly all spermatogenic cells through loss of NMD.
      However, disruption of Upf2 during postmeiotic stages resulted in decreased long
      3? UTR-mediated NMD but no interruption of exon junction-associated NMD. This
      difference in NMD targeting is possibly due to increased expression of Upf3a in
      postmeiotic germ cells that antagonizes the functions of Upf3b and somehow favors
      long 3? UTR-mediated NMD. Tying these all together, loss of Tdrd6, a structural
      component of the germ cell-specific cytoplasmic structures called chromatoid
      bodies, also resulted in loss of long 3? UTR-mediated NMD by interfering with
      UPF1/UPF2 interactions, delocalizing UPF1, and destroying chromatoid body
      integrity. These results suggest that chromatoid bodies play a specialized role
      in modulating the NMD machinery in postmeiotic spermatids.

PMID- 28444147
TI  - Hepatitis C Virus-Associated Alterations in Lipid and Lipoprotein Levels: Helpful
      or Harmful to the Heart?

PMID- 28444149
TI  - First 2 Extensively Drug-Resistant Tuberculosis Cases From Myanmar Treated With
      Bedaquiline.

PMID- 28444148
TI  - Risk of Acute Myocardial Infarction Among Hepatitis C Virus (HCV)-Positive and
      HCV-Negative Men at Various Lipid Levels: Results From ERCHIVES.
AB  - Background: Risk of acute myocardial infarction (AMI) among hepatitis C virus
      (HCV)-positive versus HCV-negative persons with similar lipid levels is unknown.
      We determined incident AMI rates among HCV-positive and HCV-negative men among
      various lipid strata. Methods: We created a propensity score matched (PSM) cohort
      and a low cardiovascular disease (CVD) risk cohort. Primary outcome was incident
      AMI rates by HCV status in each lipid strata using National Cholesterol Program
      guidelines for lipid strata. Results: We identified 85863 HCV-positive and HCV
      negative men in the PSM population. The incidence rates/1000 patient-years (95%
      confidence interval [CI]) for AMI among total cholesterol (TC) 200-239 stratum
      were 5.3 (4.89, 5.71) for HCV-positive versus 4.71 (4.42, 5) for HCV-negative men
      (P = .02) and for TC >240 mg/dL were 7.38 (6.49, 8.26) versus 6.17 (5.64, 6.71)
      (P = .02). For low-density lipoprotein cholesterol (LDL) of 130-159 mg/dL, AMI
      rates were 5.44 (4.97, 5.91) for HCV-positive and 4.81 (4.48, 5.14) for HCV
      negative men (P = .03). The rise in risk with increasing lipid levels was greater
      in younger HCV-positive than in HCV-negative men (e.g., TC > 240 mg/dL: age >50
      HR 1.38 [HCV-positive] and 1.12 [HCV-negative]; age <=50 HR 1.6 [HCV-positive]
      and 1.29 [HCV-negative]), and more profoundly altered in HCV-positive men by
      lipid lowering therapy (change in HR with lipid-lowering therapy for TC >240
      mg/dL from 1.82 to 1.19 [HCV-positive] from 1.48 to 1.03 [HCV-negative]).
      Conclusions: HCV-positive men have a higher risk of AMI than HCV-negative men at
      higher TC/LDL levels; this risk is more pronounced at a younger age. Lipid
      lowering therapy significantly reduces this risk, with more profound reduction
      among HCV-positive versus HCV-negative men at similar lipid levels.

PMID- 28444150
TI  - Optoacoustic diagnostic modality: from idea to clinical studies with highly
      compact laser diode-based systems.
AB  - Optoacoustic (photoacoustic) diagnostic modality is a technique that combines
      high optical contrast and ultrasound spatial resolution. We proposed using the
      optoacoustic technique for a number of applications, including cancer detection,
      monitoring of thermotherapy (hyperthermia, coagulation, and freezing), monitoring
      of cerebral blood oxygenation in patients with traumatic brain injury, neonatal
      patients, fetuses during late-stage labor, central venous oxygenation monitoring,
      and total hemoglobin concentration monitoring as well as hematoma detection and
      characterization. We developed and built optical parametric oscillator-based
      systems and multiwavelength, fiber-coupled highly compact, laser diode-based
      systems for optoacoustic imaging, monitoring, and sensing. To provide sufficient
      output pulse energy, a specially designed fiber-optic system was built and
      incorporated in ultrasensitive, wideband optoacoustic probes. We performed
      preclinical and clinical tests of the systems and the optoacoustic probes in
      backward mode for most of the applications and in forward mode for the breast
      cancer and cerebral applications. The high pulse energy and repetition rate
      allowed for rapid data acquisition with high signal-to-noise ratio from cerebral
      blood vessels, such as the superior sagittal sinus, central veins, and peripheral
      veins and arteries, as well as from intracranial hematomas. The optoacoustic
      systems were capable of automatic, real-time, continuous measurements of blood
      oxygenation in these blood vessels.

PMID- 28444151
TI  - Photoacoustic imaging probe for detecting lymph nodes and spreading of cancer at
      various depths.
AB  - We propose a compact and easy to use photoacoustic imaging (PAI) probe structure
      using a single strand of optical fiber and a beam combiner doubly reflecting
      acoustic waves for convenient detection of lymph nodes and cancers. Conventional
      PAI probes have difficulty detecting lymph nodes just beneath the skin or
      simultaneously investigating lymph nodes located in shallow as well as deep
      regions from skin without any supplementary material because the light and
      acoustic beams are intersecting obliquely in the probe. To overcome the
      limitations and improve their convenience, we propose a probe structure in which
      the illuminated light beam axis coincides with the axis of the ultrasound. The
      developed PAI probe was able to simultaneously achieve a wide range of images
      positioned from shallow to deep regions without the use of any supplementary
      material. Moreover, the proposed probe had low transmission losses for the light
      and acoustic beams. Therefore, the proposed PAI probe will be useful to easily
      detect lymph nodes and cancers in real clinical fields.

PMID- 28444152
TI  - Off-axis holographic laser speckle contrast imaging of blood vessels in tissues.
AB  - Laser speckle contrast imaging (LSCI) has become one of the most common tools for
      functional imaging in tissues. Incomplete theoretical description and
      sophisticated interpretation of measurement results are completely sidelined by a
      low-cost and simple hardware, fastness, consistent results, and repeatability. In
      addition to the relatively low measuring volume with around 700 ?? ? m of the
      probing depth for the visible spectral range of illumination, there is no depth
      selectivity in conventional LSCI configuration; furthermore, in a case of high NA
      objective, the actual penetration depth of light in tissues is greater than depth
      of field (DOF) of an imaging system. Thus, the information about these out-of
      focus regions persists in the recorded frames but cannot be retrieved due to
      intensity-based registration method. We propose a simple modification of LSCI
      system based on the off-axis holography to introduce after-registration
      refocusing ability to overcome both depth-selectivity and DOF problems as well as
      to get the potential possibility of producing a cross-section view of the
      specimen.

PMID- 28444153
TI  - Computed tomography derived fractional flow reserve testing in stable patients
      with typical angina pectoris: influence on downstream rate of invasive coronary
      angiography.
AB  - Aims: To assess the use of downstream coronary angiography (ICA) and short-term
      safety of frontline coronary CT angiography (CTA) with selective CT-derived
      fractional flow reserve (FFRCT) testing in stable patients with typical angina
      pectoris. Methods and results: Between 1 January 2016 and 30 June 2016 all
      patients (N = 774) referred to non-emergent ICA or coronary CTA at Aarhus
      University Hospital on a suspicion of CAD had frontline CTA performed. Downstream
      testing and treatment within 3 months and adverse events >=90 days were
      registered. Patients were divided into two groups according to the presence of
      typical angina pectoris, which according to local practice would have resulted in
      referral to ICA, (low-intermediate-risk, n = 593 [76%]; high-risk, n = 181 [24%])
      with mean pre-test probability of CAD of 31 +/- 16% and 67 +/- 16%, respectively.
      Coronary CTA was performed in 745 (96%) patients in whom FFRCT was prescribed in
      212 (28%) patients. In the high- vs. low-intermediate-risk group, ICA was
      cancelled in 75% vs. 91%. Coronary revascularization was performed more
      frequently in high-risk than in low-intermediate-risk patients, 76% vs. 52% (P =
      0.03). Mean follow-up time was 157 +/- 50 days. Serious clinical events occurred
      in four patients, but not in any patients with cancelled ICA by coronary CTA with
      selective FFRCT testing. Conclusion: Frontline coronary CTA with selective FFRCT
      testing in stable patients with typical angina pectoris in real-world practice is
      associated with a high rate of safe cancellation of planned ICAs.

PMID- 28444154
TI  - Infectivity of an Asymptomatic Patient With Middle East Respiratory Syndrome
      Coronavirus Infection.
AB  - During the MERS outbreak in Korea, one case of asymptomatic or mild MERS-CoV
      infection was noted. Eighty-two persons were exposed to the case without
      protection. They were isolated and RT-PCR and serology for MERS were performed.
      There was no transmission through an asymptomatic MERS case in this study.

PMID- 28444155
TI  - Hospitalization Rates Among People With HIV/AIDS in New York City, 2013.
AB  - Background: Hospitalizations are an important indicator of healthcare quality and
      access for people with human immunodeficiency virus (HIV) and acquired immune
      deficiency syndrome (AIDS). This study assesses hospitalization rates among
      people with HIV/AIDS in New York City. Methods: We performed a deterministic
      match between people in the New York City HIV surveillance registry alive as of 1
      January 2013 and diagnosed with HIV as of 31 December 2013 and patient-level
      inpatient hospitalization records during 2013. Event-level data were analyzed to
      determine characteristics of and reasons for hospitalizations. Primary diagnoses
      were classified using the International Classification of Diseases, Ninth
      Revision, Clinical Modification. We estimated hospitalization rates as the number
      of hospitalizations per 100 person-years for all causes, AIDS-defining illnesses,
      and non-AIDS-defining infections. Results: Nearly one-fifth of hospitalizations
      were attributed to non-AIDS-defining infections, whereas AIDS-defining illness
      diagnoses were infrequent (3.6% of hospitalizations). Other common causes were
      cardiovascular (10.9%) and substance use (9.8%). The estimated all-cause
      hospitalization rate was 36.7 per 100 person-years. Higher all-cause
      hospitalization rates were observed among females (46.8 per 100 person-years),
      Black and Latino/Hispanic people (41.8 and 39.5 per 100 person-years,
      respectively), people living in high-poverty neighborhoods (47.4 per 100 person
      years), and people with a history of injection drug use (74.9 per 100 person
      years). The estimated AIDS-defining illness and non-AIDS-defining infection
      hospitalization rates were 1.3 and 7.2 per 100 person-years, respectively.
      Conclusions: People with HIV in New York City were frequently hospitalized. While
      AIDS-defining illnesses were relatively rare, non-AIDS-defining infection
      hospitalizations were more common. Disparities in hospitalization rates indicate
      a need for targeted improved primary care and comorbid disease management.

PMID- 28444156
TI  - The Immunogenicity of Fractional Intradermal Doses of the Inactivated Poliovirus
      Vaccine Is Associated With the Size of the Intradermal Fluid Bleb.
AB  - The immunogenicity of fractional (one-fifth, 0.1 mL) intradermal doses of the
      inactivated poliovirus vaccine (ID fIPV) is positively correlated with the size
      of the intradermal fluid bleb. Training of vaccinators for campaign and routine
      ID fIPV administration should focus on generating an 8- to 10-mm bleb with each
      injection. Clinical Trials Registration NCT01847872.

PMID- 28444158
TI  - Reactivation of Hepatitis B Virus Following Treatment of Hepatitis C Virus
      Infection in Coinfected Patients.

PMID- 28444157
TI  - Risk of Congenital Syphilis (CS) Following Treatment of Maternal Syphilis:
      Results of a CS Control Program in China.
AB  - Background: Early screening for syphilis among pregnant women and the effective
      treatment of maternal syphilis is fundamental to prevent congenital syphilis
      (CS). Methods: We obtained data from the Shenzhen Program for Prevention of CS
      (SPPCS) and estimated incidence rates of CS among infants born to syphilis
      seropositive women treated with different regimens or untreated for maternal
      syphilis. Results: A total of 4746 matched cases of syphilis-seropositive mothers
      and their infants were included for analyses, and 162 infants were diagnosed with
      CS, providing an overall incidence of 3.41% (95% confidence interval [CI], 2.91%
      3.98%). Among infants born to syphilis-seropositive women who had syphilis and
      were adequately treated before pregnancy, the incidence was 0.22% (95% CI, .05%
      .66%). There were 159 cases of CS occurring in 3519 infants born to women who
      were syphilis-seropositive during their pregnancies, for an incidence of 4.52%
      (95% CI, 3.84%-5.28%). The incidence of CS was 1.82%-11.90% lower among infants
      born to the women treated with early benzathine penicillin G (BPG) compared with
      those treated with late BPG (adjusted odds ratio [aOR], 8.06 [95% CI, 2.93
      22.21]; P < .001), other antibiotics (aOR, 7.71 [95% CI, .86-69.28]; P = .068),
      or those untreated (aOR, 68.28 [95% CI, 29.64-157.28]; P < .001). The incidence
      rates were 0.22% (95% CI, .06%-.80%) and 0.59% (95% CI, .35%-1.02%) in infants
      born to women treated with 2 courses and 1 course of BPG, respectively,
      corresponding to a risk difference of 0.37% (aOR, 1.74; 95% CI, .37-8.26).
      Conclusions: Treatment of syphilis-seropositive pregnant women with 1 course of
      intramuscular BPG before 28 gestational weeks is critical for prevention of CS.

PMID- 28444159
TI  - A strange nature of right ventricular tumour: the first case report of osseous
      metaplasia in the heart.

PMID- 28444160
TI  - Echo-Doppler estimation of left ventricular filling pressure: results of the
      multicentre EACVI Euro-Filling study.
AB  - Aims: The present Euro-Filling report aimed at comparing the diagnostic accuracy
      of the 2009 and 2016 echocardiographic grading algorithms for predicting
      invasively measured left ventricular filling pressure (LVFP). Method and results:
      A total of 159 patients who underwent simultaneous evaluation of echo estimates
      of LVFP and invasive measurements of LV end-diastolic pressure (LVEDP) were
      enrolled at nine EACVI centres. Thirty-nine (25%) patients had a reduced LV
      ejection fraction (<50%), 77 (64%) were in NYHA >= II, and 85 (53%) had coronary
      artery disease. Sixty-four (40%) patients had elevated LVEDP (>=15 mmHg). Taken
      individually, all echocardiographic Doppler estimates of LVFP (E/A, E/e', left
      atrial volume, tricuspid regurgitation jet velocity) were marginally correlated
      with LVEDP. By using the 2016 recommendations, 65% of patients with normal non
      invasive estimate of LVFP had normal LVEDP, while 79% of those with elevated non
      invasive LVFP had elevated invasive LVEDP. By using 2009 recommendations, 68% of
      the patients with normal non-invasive LVFP had normal LVEDP, while 55% of those
      with elevated non-invasive LVFP had elevated LVEDP. The 2016 recommendations
      (sensitivity 75%, specificity 74%, positive predictive value 39%, negative
      predictive value 93%, AUC 0.78) identified slightly better patients with elevated
      invasive LVEDP (>= 15 mmHg) as compared with the 2009 recommendations
      (sensitivity 43%, specificity 75%, positive predictive value 49%, negative
      predictive value 71%, AUC 0.68). Conclusion: The present Euro-Filling study
      demonstrates that the new 2016 recommendations for assessing LVFP non-invasively
      are fairly reliable and clinically useful, as well as superior to the 2009
      recommendations in estimating invasive LVEDP.

PMID- 28444161
TI  - Odor Perception by Dogs: Evaluating Two Training Approaches for Odor Learning of
      Sniffer Dogs.
AB  - In this study, a standardized experimental set-up with various combinations of
      herbs as odor sources was designed. Two training approaches for sniffer dogs were
      compared; first, training with a pure reference odor, and second, training with a
      variety of odor mixtures with the target odor as a common denominator. The
      ability of the dogs to identify the target odor in a new context was tested. Six
      different herbs (basil, St. John's wort, dandelion, marjoram, parsley, ribwort)
      were chosen to produce reference materials in various mixtures with (positive)
      and without (negative) chamomile as the target odor source. The dogs were trained
      to show 1 of 2 different behaviors, 1 for the positive, and 1 for the negative
      sample as a yes/no task. Tests were double blind with one sample presented at a
      time. In both training approaches, dogs were able to detect chamomile as the
      target odor in any presented mixture with an average sensitivity of 72% and a
      specificity of 84%. Dogs trained with odor mixture containing the target odor had
      more correct indications in the transfer task.

PMID- 28444163
TI  - Corrigendum to: '2016 ESC/EAS Guidelines for the Management of Dyslipidaemias'.

PMID- 28444162
TI  - Coronary artery disease severity and long-term cardiovascular risk in patients
      with myocardial infarction: a Danish nationwide register-based cohort study.
AB  - Aim: Long-term prognostic impact of coronary artery disease (CAD) severity in
      stable post-myocardial infarction (MI) patients is not well known. We examined
      the impact of CAD severity and co-morbidity on the long-term (1 year and beyond)
      risk of cardiovascular events post-MI. Methods and results: From nationwide
      administrative and clinical registers, we identified 55 747 MI patients, during
      2004-2010, who had not experienced subsequent MI, stroke, or death within 7 days
      post-discharge. The risk for primary composite endpoint (MI, stroke, or
      cardiovascular death) was estimated for the first 365 days after MI (index MI)
      and from day 366 to study completion (stable post-MI population), corresponding
      to a mean follow-up of 3.6 (2.2) years. Risk was assessed using cumulative
      incidence, multivariable adjusted logistic regression and Cox proportional
      hazards models. The 1-year cumulative incidence for primary endpoint was 20.0%
      [95% confidence interval (CI), (19.6-20.3)]. Correspondingly, the 4-year
      cumulative incidence for primary endpoint was 21.0% (95% CI, 20.6-21.4) in
      patients without events on the first year. In multivariable models with no
      significant stenosis as reference, CAD severity was the most important risk
      factor for cardiovascular events the first 365 days [left main stenosis (LMS):
      odds ratio and 95% CI, 4.37, 3.69-5.17; 3-vessel disease (VD), 4.18, 3.66-4.77; 2
      VD, 3.23, 2.81-3.72; 1-VD, 2.12,-1.85-2.43] and remained from day 366 to study
      completion [LMS: hazard ratio and 95% CI, 1.91, 1.64-2.22; 3-VD, 1.85,1.65-2.07;
      2-VD, 1.55, 1.38-1.74; 1-VD, 1.30, 1.16-1.45]. Conclusion: Despite contemporary
      treatment at baseline, stable post-MI patients' 4-year outcome was similar to 1
      year outcome after MI, and CAD severity remained a critical risk factor the first
      year and thereafter.

PMID- 28444164
TI  - Vena contracta area for severity grading in functional and degenerative mitral
      regurgitation: a transoesophageal 3D colour Doppler analysis in 500 patients.
AB  - Aims: Vena contracta area (VCA3D), derived by 3D colour Doppler echocardiography,
      has already been validated against cardiac magnetic resonance imaging, but the
      number of clinical studies to define cut-off values for grading of mitral
      regurgitation (MR) is limited. Aim of the study was to assess VCA3D in a large
      population of patients with functional (FMR) and degenerative MR (DMR). Methods
      and results: Transoesophageal echocardiography was performed in 500 patients with
      MR. The following 2D parameters were assessed for grading of MR: vena contracta
      width, effective regurgitant orifice area (EROAPISA), and regurgitation volume
      (RVPISA). VCA3D and the corresponding regurgitation volume (RVVCA) were
      quantified using 3D colour Doppler loop and CW Doppler tracing of the regurgitant
      jet. In 104 patients a 3D dataset of the left ventricle (LV) and the left
      ventricular outflow tract (LVOT) was acquired. As a reference method,
      regurgitation volume (RV3D) was calculated as difference between LV overall and
      LVOT stroke volumes. For prediction of severe MR, VCA3D yielded higher values of
      area under the ROC curve compared to EROAPISA (overall patient group 0.98 for
      VCA3D vs. 0.90 for EROAPISA, P < 0.001; FMR group 0.97 for VCA3D vs. 0.92 for
      EROAPISA, P = 0.002). RVVCA correlated closer with RV3D compared to RVPISA (r =
      0.96 for RVPISA, r = 0.79 for RVPISA). Conclusion: This study delivers cut-off
      values for VCA3D in patients with different types of MR. VCA3D is a robust
      parameter for quantification of MR, showing a good correlation with the reference
      method using 3D datasets of LV.

PMID- 28444165
TI  - Proinflammatory mediators related to orthodontically induced periapical root
      resorption in rat mandibular molars.
AB  - Objectives: The early phase of orthodontic tooth movement involves acute
      inflammatory response that may induce bone resorption. The aim of this study was
      to localize and quantify cells in the periodontium expressing proinflammatory
      mediators during orthodontically induced periapical root resorption of the rat
      mandibular molars. Materials and methods: The levels of proinflammatory cytokines
      interleukin-1 (IL-1) alpha and beta, tumor necrosis factor-alpha (TNF-alpha),
      inflammatory enzymes cyclooxygenase (COX) 1 and 2, and their product
      prostaglandin E2 (PGE2) in the root resorption site were compared to those in the
      corresponding area of the untreated periodontal ligament (PDL) of physiologically
      drifting teeth. Continuous heavy orthodontic force was applied to the mandibular
      first molar for 8 and 15 days while in occlusion to induce root resorption.
      Frozen sections including root resorption lacunae were analyzed for the activity
      of non-specific esterase (NSE) and tartrate-resistant acid phosphatase (TRAP) by
      enzyme histochemistry and for the expression of IL-1alpha, IL-1beta, TNF-alpha,
      COX-1, COX-2, and PGE2 by immunohistochemistry. Results: The active root
      resorption lacunae had significantly more TRAP-positive multinucleated
      odontoclasts, whereas the number of NSE-positive cells of the monocyte-macrophage
      lineage did not differ from that in the control PDL. Several types of periodontal
      cells exhibited a significant increase in the expression of IL-1alpha, IL-1beta,
      TNF-alpha, COX-2, and PGE2 in the root resorption zone, while COX-1 was rarely
      detected. Conclusions: These data suggest that proinflammatory mediators
      expressed in periodontal cells may synergistically promote apical root resorption
      in response to continuous heavy mechanical force applied to teeth.

PMID- 28444166
TI  - The Effect of a Piperacillin/Tazobactam Shortage on Antimicrobial Prescribing and
      Clostridium difficile Risk in 88 US Medical Centers.
AB  - Background: Anti-infective shortages are a pervasive problem in the United
      States. The objective of this study was to identify any associations between
      changes in prescribing of antibiotics that have a high risk for CDI during a
      piperacillin/tazobactam (PIP/TAZO) shortage and hospital-onset Clostridium
      difficile infection (HO-CDI) risk in 88 US medical centers. Methods: We analyzed
      electronically captured microbiology and antibiotic use data from a network of US
      hospitals from July 2014 through June 2016. The primary outcome was HO-CDI rate
      and the secondary outcome was changes in antibiotic usage. We fit a Poisson model
      to estimate the risk of HO-CDI associated with PIP/TAZO shortage that were
      associated with increased high-risk antibiotic use while controlling for hospital
      characteristics. Results: A total of 88 hospitals experienced PIP/TAZO shortage
      and 72 of them experienced a shift toward increased use of high-risk antibiotics
      during the shortage period. The adjusted relative risk (RR) of HO-CDI for
      hospitals experiencing a PIP/TAZO shortage was 1.03 (95% confidence interval
      [CI], .85-1.26; P = .73). The adjusted RR of HO-CDI for hospitals that both
      experienced a shortage and also showed a shift toward increased use of high-risk
      antibiotics was 1.30 (95% CI, 1.03-1.64; P < .05). Conclusions: Hospitals that
      experienced a PIP/TAZO shortage and responded to that shortage by shifting
      antibiotic usage toward antibiotics traditionally known to place patients at
      greater risk for CDI experienced greater HO-CDI rates; this highlights an
      important adverse effect of the PIP/TAZO shortage and the importance of
      antibiotic stewardship when mitigating drug shortages.

PMID- 28444167
TI  - Electrical cardiac injuries: current concepts and management.
AB  - Electrical injuries are a commonly encountered hazard in both the home and
      workplace. However, clinicians are often uncomfortable when faced with the
      patient who presents with an electric shock due to sparse literature and lack of
      systematic recommendations on this topic. Electrical injuries can range from
      minor skin burns to life threatening internal organ damage. A thorough clinical
      assessment to ascertain the path of current through the body and possible
      internal injury is essential. The main concern in an apparently stable individual
      after an electric shock is the potential for delayed occurrence of cardiac
      arrhythmias which will require monitoring in the intensive care setting. While it
      may be reasonable to discharge home from the emergency room selected patients
      with low voltage injuries, absence of syncope and a normal ECG, others may
      require monitoring for at least 24 h. Public education and increasing workplace
      as well as home safety measures are key steps in prevention. The present review
      summarizes current knowledge in pathophysiology, manifestations and management of
      electrical injuries, with specific focus on cardiac effects.

PMID- 28444168
TI  - Mechanical versus bioprosthetic aortic valve replacement.
AB  - Mechanical valves used for aortic valve replacement (AVR) continue to be
      associated with bleeding risks because of anticoagulation therapy, while
      bioprosthetic valves are at risk of structural valve deterioration requiring
      reoperation. This risk/benefit ratio of mechanical and bioprosthetic valves has
      led American and European guidelines on valvular heart disease to be consistent
      in recommending the use of mechanical prostheses in patients younger than 60
      years of age. Despite these recommendations, the use of bioprosthetic valves has
      significantly increased over the last decades in all age groups. A systematic
      review of manuscripts applying propensity-matching or multivariable analysis to
      compare the usage of mechanical vs. bioprosthetic valves found either similar
      outcomes between the two types of valves or favourable outcomes with mechanical
      prostheses, particularly in younger patients. The risk/benefit ratio and choice
      of valves will be impacted by developments in valve designs, anticoagulation
      therapy, reducing the required international normalized ratio, and transcatheter
      and minimally invasive procedures. However, there is currently no evidence to
      support lowering the age threshold for implanting a bioprosthesis. Physicians in
      the Heart Team and patients should be cautious in pursuing more bioprosthetic
      valve use until its benefit is clearly proven in middle-aged patients.

PMID- 28444171
TI  - On the origins of Balkan endemics: the complex evolutionary history of the Cyanus
      napulifer group (Asteraceae).

PMID- 28444170
TI  - Neuronal Activity, TGFbeta-Signaling and Unpredictable Chronic Stress Modulate
      Transcription of Gadd45 Family Members and DNA Methylation in the Hippocampus.
AB  - Neuronal activity is altered in several neurological and psychiatric diseases.
      Upon depolarization not only neurotransmitters are released but also cytokines
      and other activators of signaling cascades. Unraveling their complex implication
      in transcriptional control in receiving cells will contribute to understand
      specific central nervous system (CNS) pathologies and will be of therapeutically
      interest. In this study we depolarized mature hippocampal neurons in vitro using
      KCl and revealed increased release not only of brain-derived neurotrophic factor
      (BDNF) but also of transforming growth factor beta (TGFB). Neuronal activity
      together with BDNF and TGFB controls transcription of DNA modifying enzymes
      specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b,
      and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome
      analyses revealed less DNA methylation upon KCl treatment. Psychiatric disorder
      related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are
      transcriptionally activated and demethylated upon neuronal activation. To analyze
      whether misexpression of Gadd45 family members are associated with psychiatric
      diseases, we applied unpredictable chronic mild stress (UCMS) as established
      model for depression to mice. UCMS led to reduced expression of Gadd45 family
      members. Taken together, our data demonstrate that Gadd45 family members are new
      putative targets for UCMS treatments.

PMID- 28444169
TI  - Androgen Receptor Regulation of Local Growth Hormone in Prostate Cancer Cells.
AB  - Prostate cancer (PCa) growth is mainly driven by androgen receptor (AR), and
      tumors that initially respond to androgen deprivation therapy (ADT) or AR
      inhibition usually relapse into a more aggressive, castration-resistant PCa
      (CRPC) stage. Circulating growth hormone (GH) has a permissive role in PCa
      development in animal models and in human PCa xenograft growth. As GH and GH
      receptor (GHR) are both expressed in PCa cells, we assessed whether prostatic GH
      production is linked to AR activity and whether GH contributes to the castration
      resistant phenotype. Using online datasets, we found that GH is highly expressed
      in human CRPC. We observed increased GH expression in castration-resistant C4-2
      compared with castration-sensitive LNCaP cells as well as in enzalutamide
      (MDV3100)-resistant (MDVR) C4-2B (C4-2B MDVR) cells compared with parental C4-2B.
      We describe a negative regulation of locally produced GH by androgens/AR in PCa
      cells following treatment with AR agonists (R1881) and antagonists (enzalutamide,
      bicalutamide). We also show that GH enhances invasive behavior of CRPC 22Rv1
      cells, as reflected by increased migration, invasion, and anchorage-independent
      growth, as well as expression of matrix metalloproteases. Moreover, GH induces
      expression of the AR splice variant 7, which correlates with antiandrogen
      resistance, and also induces insulinlike growth factor 1, which is implicated in
      PCa progression and ligand-independent AR activation. In contrast, blockade of GH
      action with the GHR antagonist pegvisomant reverses these effects both in vitro
      and in vivo. GH induction following ADT or AR inhibition may contribute to CRPC
      progression by bypassing androgen growth requirements.

PMID- 28444172
TI  - Risk of venous thromboembolism in patients with psoriatic arthritis, psoriasis
      and rheumatoid arthritis: a general population-based cohort study.
AB  - Aims: To determine the risk of venous thromboembolism (VTE) defined as the
      combined endpoint of deep venous thrombosis (DVT) and pulmonary embolism (PE)
      among patients with psoriatic arthritis (PsA), psoriasis and rheumatoid arthritis
      (RA) compared with population controls. Methods and results: A cohort study was
      conducted in a primary care medical record database in the UK with data from 1994
      2014 among patients with PsA, RA, or psoriasis. Cox proportional hazards models
      were used to calculate the relative hazards for DVT, PE, and VTE. An interaction
      with disease modifying anti-rheumatic drugs (DMARD) was hypothesized a priori and
      was significant. Patients with PsA (n = 12 084), RA (n = 51 762), psoriasis (n =
      194 288) and controls (n = 1 225 571) matched on general practice and start date
      were identified. Patients with RA (with and without a DMARD prescription) and
      patients with mild psoriasis had significantly elevated risks of VTE (HR 1.35,
      1.29, and 1.07, respectively) after adjusting for traditional risk factors.
      Severe psoriasis and PsA prescribed a DMARD had an elevated but not statistically
      significant risk for VTE. Findings were similar for DVT. The age-and-sex-adjusted
      risk of PE was elevated in RA, severe psoriasis and PsA patients prescribed a
      DMARD. Conclusion: While systemic inflammation is a risk factor for VTE, the risk
      of VTE compared with controls is different among patients with three different
      inflammatory disorders: RA, PsA, and psoriasis.

PMID- 28444174
TI  - Catheter ablation for ventricular tachycardia in patients with cardiac
      sarcoidosis: a systematic review.
AB  - Aims: Cardiac sarcoidosis (CS) is associated with a poor prognosis. Important
      features of CS include heart failure, conduction abnormalities, and ventricular
      arrhythmias. Ventricular tachycardia (VT) is often refractory to antiarrhythmic
      drugs (AAD) and immunosuppression. Catheter ablation has emerged as a treatment
      option for recurrent VT. However, data on the efficacy and outcomes of VT
      ablation in this context are sparse. Methods and results: A systematic search was
      performed on PubMed, EMBASE, and Cochrane database (from inception to September
      2016) with included studies providing a minimum of information on CS patients
      undergoing VT ablation: age, gender, VT cycle length, CS diagnosis criteria, and
      baseline medications. Five studies reporting on 83 patients were identified. The
      mean age of patients was 50 +/- 8 years, 53/30 (males/females) with a maximum of
      56 patients receiving immunosuppressive therapy, mean ejection fraction was 39.1
      +/- 3.1% and 94% had an implantable cardioverter defibrillator in situ. The
      median number of VTs was 3 (2.6-4.9)/patient, mean cycle length of 360 ms (326
      400 ms). Hundred percent of VTs received endocardial ablation, and 18% required
      epicardial ablation. The complication rates were 4.7-6.3%. Relapse occurred in 45
      (54.2%) patients with an incidence of relapse 0.33 (95% confidence interval 0.108
      0.551, P < 0.004). Employing a less stringent endpoint (i.e. freedom from
      arrhythmia or reduction of ventricular arrhythmia burden), 61 (88.4%) patients
      improved following ablation. Conclusions: These data support the utilization of
      catheter ablation in selected CS cases resistant to medical treatment. However,
      data are derived from observational non-controlled case series, with low
      methodological quality. Therefore, future well-designed, randomized controlled
      trials, or large-scale registries are required.

PMID- 28444173
TI  - Tac1 Signaling Is Required for Sexual Maturation and Responsiveness of GnRH
      Neurons to Kisspeptin in the Male Mouse.
AB  - The tachykinins substance P (SP) and neurokinin A (Tac1) have emerged as novel
      regulators of kisspeptin/GnRH release. Recently, we documented that SP modulates
      reproductive function in the female mouse. Here, we extended this
      characterization to the male mouse. Tac1-/- male mice showed delayed puberty
      onset. They also presented significantly decreased expression levels of Pdyn
      (dynorphin) and Nos1 (nitric oxide synthase) in the mediobasal hypothalamus and
      elevated Gnrh1 levels. Unexpectedly, the response of Tac1-/- mice to central
      kisspeptin or senktide (neurokinin B receptor-agonist) administration was
      significantly decreased compared with controls, despite the preserved ability of
      GnRH neurons to stimulate luteinizing hormone release as demonstrated by central
      N-methyl-D-aspartate receptor administration, suggesting a deficit at the GnRH
      neuron level. Importantly, we demonstrated that kisspeptin receptor and SP
      receptor (NK1R) heterodimerize, indicating that changes in the SP tone could
      alter the responsiveness of GnRH neurons to kisspeptin. Finally,
      electrophysiological recordings from arcuate Kiss1 neurons showed that, although
      virtually all Kiss1 neurons responded to NKB and senktide, only half responded to
      an NK1R agonist and none to the neurokinin A receptor agonist at a 1-MUM dose. In
      summary, we provide compelling evidence for a role of Tac1 in the control of
      reproductive function in the male mouse, suggesting a predominant central action
      that may involve a change in the balance of neural factors that control GnRH
      expression.

PMID- 28444176
TI  - "J waves" induced after short coupling intervals: a manifestations of latent
      depolarization abnormality?
AB  - Aims: To confirm the presence of tachycardia-induced slur or notch in the
      terminal portion of the QRS complexes in a general patient population. Methods
      and results: A tachycardia-induced J wave was defined as a slur or notch in the
      terminal portion of the QRS complexes newly induced at short RR intervals during
      atrial premature contractions (APCs) or atrial electrical stimulation in the
      electrophysiological study (EPS). Twenty-three out of 2000 patients with general
      diseases were involved. All patients with aborted sudden cardiac death,
      ventricular fibrillation or a family history of sudden cardiac death were
      excluded. The mean age was 72 +/- 9 years, and 11 patients were male (47.8%).
      When the RR interval was shortened from 821 +/- 142 ms to 464 +/- 52 ms in the
      conducted APCs (P < 0.0001), J waves became diagnostic (0.02 +/- 0.03 mV to 0.20
      +/- 0.07 mV, P < 0.0001). J waves were confined to the inferior leads in 22
      (95.7%) patients and were notched in 11 (47.8%) and slurred in 12 (52.2%)
      patients. The induction of J waves was accompanied by visible changes of the QRS
      morphology. When the post-APC RR interval was prolonged to 992 +/- 305 ms (P =
      0.0154 vs. baseline), the J waves were similar to baseline levels. During the
      EPS, J wave induction was confirmed during atrial stimulation. There were no
      characteristic clinical or ECG features in the patients with tachycardia-induced
      J waves. Conclusions: J waves can be newly induced by short RR intervals in a
      general patient population, and a conduction delay is the likely mechanism
      causing such J waves.

PMID- 28444175
TI  - Predictive value of telomere length on outcome following acute myocardial
      infarction: evidence for contrasting effects of vascular vs. blood oxidative
      stress.
AB  - Aims: Experimental evidence suggests that telomere length (TL) is shortened by
      oxidative DNA damage, reflecting biological aging. We explore the value of blood
      (BTL) and vascular TL (VTL) as biomarkers of systemic/vascular oxidative stress
      in humans and test the clinical predictive value of BTL in acute myocardial
      infarction (AMI). Methods and results: In a prospective cohort of 290 patients
      surviving recent AMI, BTL measured on admission was a strong predictor of all
      cause [hazard ratio (HR) [95% confidence interval (CI)]: 3.21 [1.46-7.06], P =
      0.004] and cardiovascular mortality (HR [95% CI]: 3.96 [1.65-9.53], P = 0.002) 1
      year after AMI (for comparisons of short vs. long BTL, as defined by a T/S ratio
      cut-off of 0.916, calculated using receiver operating characteristic analysis; P
      adjusted for age and other predictors). To explore the biological meaning of
      these findings, BTL was quantified in 727 consecutive patients undergoing
      coronary artery bypass grafting (CABG), and superoxide (O2.-) was measured in
      peripheral blood mononuclear cells (PBMNC). VTL/vascular O2.- were quantified in
      saphenous vein (SV) and mammary artery (IMA) segments. Patients were genotyped
      for functional genetic polymorphisms in P22ph degrees x (activating NADPH
      oxidases) and vascular smooth muscle cells (VSMC) selected by genotype were
      cultured from vascular tissue. Short BTL was associated with high O2.- in PBMNC
      (P = 0.04) but not in vessels, whereas VTL was related to O2.- in IMA (rho = 
      0.49, P = 0.004) and SV (rho = -0.52, P = 0.01). Angiotensin II (AngII)
      incubation of VSMC (30 days), as a means of stimulating NADPH-oxidases, increased
      O2.- and reduced TL in carriers of the high-responsiveness P22ph degrees x
      alleles (P = 0.007). Conclusion: BTL predicts cardiovascular outcomes post-AMI,
      independently of age, whereas VTL is a tissue-specific (rather than a global)
      biomarker of vascular oxidative stress. The lack of a strong association between
      BTL and VTL reveals the importance of systemic vs. vascular factors in
      determining clinical outcomes after AMI.

PMID- 28444177
TI  - Single centre experience with transapical transcatheter mitral valve
      implantation.
AB  - OBJECTIVES: A transcatheter heart valve technique can be used in failed mitral
      valve repairs with annuloplasty rings, deterioriated bioprostheses and in mitral
      annular calcification, all serving as 'docking stations' for balloon-expandable
      valves. Specially designed transcatheter mitral valve platforms are used in
      ongoing studies for native mitral valve regurgitation. We present our single
      centre experience with transcatheter mitral valve implantation-transapical
      approach procedures in eleven patients. METHODS: Eleven patients were treated
      between 2011 and 2016. They had severe mitral regurgitation due to either failed
      repair annuloplasty rings (N = 6), failed bioprostheses (N = 2) or in the native
      valve (N = 3), all at high risk for open mitral valve surgery. Three different
      types of transcatheter valves were used: (1) the SAPIEN XT/SAPIEN 3, (2) the
      Lotus valve and (3) a Tendyne transcatheter mitral valve. Computed tomography
      reconstruction, echocardiography, 3D printing and bench tests were done in the
      preoperative evaluation and procedural planning. Transapical approach access was
      performed via a left minithoracotomy. RESULTS: Implantation success was 100% with
      no left ventricular outflow tract obstruction. Good haemodynamics and improved
      New York Heart Association class were demonstrated in all patients. One patient
      died before 30 days due to sepsis. One patient had a valve thrombosis when
      switching from Coumadin to new oral anticoagulant and had a second valve
      implanted into the first one as a 'valve-in-valve' procedure. CONCLUSIONS: The
      transapical approach is a safe and straight forward procedure for accessing the
      mitral valve. 'Transcatheter aortic valve implantation' prostheses may be used in
      redo surgery due to an already sufficient 'docking station'. These specially
      designed new prostheses may be beneficial for addressing mitral valve
      regurgitation, but are still under evaluation. Anticoagulation is mandatory.

PMID- 28444179
TI  - A novel method for superimposition and measurements on maxillary digital 3D
      models-studies on validity and reliability.
AB  - Background: Serial 3D models can be used to analyze changes, but correct
      superimposition is crucial before measurements can be assessed. Earlier studies
      show that every palatal structure changes due to growth or treatment. Here, we
      describe a new method that uses an algorithm-based analysis to perform
      superimpositions and measurements in maxillary 3D models. This method can be used
      to identify deformations. In a second step, only unchanged areas are used for
      superimposition. Objectives: This study investigates the validity and reliability
      of this novel method. Methods: Digital 3D models from 16 cases were modified by
      an independent 3D engineer to simulate space closure and growth. True values for
      tooth movements were available as reference. Measurements and repeated
      measurements were performed by four observers. Results: The total tooth movement
      had an absolute mean error of 0.0225 mm (SD 0.03). The intraclass correlation
      coefficient (ICC) was 0.9996. Rotational measurements had an absolute mean error
      of 0.0291 degrees (SD 0.04 degrees) and an ICC of 0.9999. Limitations: Serial
      models need to be taken with a moderate interval (1 to 2 years). Obvious changed
      areas in the palate need to be cropped before processing the models. Conclusion:
      The tested method is valid and reliable with excellent accuracy and precision
      even when changes through growth or orthodontic treatment occur.

PMID- 28444178
TI  - Shortening cardioplegic arrest time in patients undergoing combined coronary and
      valve surgery: results from a multicentre randomized controlled trial: the SCAT
      trial.
AB  - OBJECTIVES: Combined coronary artery bypass grafting and valve surgery requires a
      prolonged period of cardioplegic arrest (CA) predisposing to myocardial injury
      and postoperative cardiac-specific complications. The aim of this trial was to
      reduce the CA time in patients undergoing combined coronary artery bypass
      grafting and valve surgery and assess if this was associated with less myocardial
      injury and related complications. METHODS: Participants were randomized to (i)
      coronary artery bypass grafting performed on the beating heart with
      cardiopulmonary bypass support followed by CA for the valve procedure (hybrid) or
      (ii) both procedures under CA (conventional). To assess complications related to
      myocardial injury, we used the composite of death, myocardial infarction,
      arrhythmia, need for pacing or inotropes for >12 h. To assess myocardial injury,
      we used serial plasma troponin T and markers of metabolic stress in myocardial
      biopsies. RESULTS: Hundred and sixty patients (80 hybrid and 80 conventional)
      were randomized. Mean age was 66.5 years and 74% were male. Valve procedures
      included aortic (61.8%) and mitral (33.1%) alone or in combination (5.1%). CA
      time was 16% lower in the hybrid group [median 98 vs 89 min, geometric mean ratio
      (GMR) 0.84, 95% confidence interval (CI) 0.77-0.93, P  = 0.0004]. Complications
      related to myocardial injury occurred in 131/160 patients (64/80 conventional,
      67/80 hybrid), odds ratio 1.24, 95% CI 0.54-2.86, P  = 0.61. Release of troponin
      T was similar between groups (GMR 1.04, 95% CI 0.87-1.24, P  = 0.68). Adenosine
      monophosphate was 28% lower in the hybrid group (GMR 0.72, 95% CI 0.51-1.02, P  =
      0.056). CONCLUSIONS: The hybrid procedure reduced the CA time but myocardial
      injury outcomes were not superior to conventional approach. TRIAL REGISTRATION:
      ISRCTN65770930.

PMID- 28444180
TI  - Left bundle branch block: from cardiac mechanics to clinical and diagnostic
      challenges.
AB  - Left bundle branch block (LBBB) results in an altered pattern of left ventricular
      (LV) activation and subsequent contraction, causing remarkable changes in LV
      mechanics, perfusion and workload and ultimately leading to pathologic cardiac
      remodelling. Clinical and diagnostic notions about the LBBB phenomenon had
      evolved from just an electrocardiographic pattern to a critically important
      finding affecting diagnostic and clinical management of many patients and
      adversely influencing their outcomes. Recent advances in imaging techniques
      significantly improved the assessment of patients with LBBB and provided
      additional insights into pathophysiological mechanisms of LV remodelling. In the
      current review we summarized currently available data on the LBBB epidemiology,
      diagnosis, its impact on clinical management and prognosis, and the role and
      place of various imaging modalities in assessing cardiac mechanics and perfusion
      abnormalities, as well as their potential implications for diagnostic and
      treatment strategies.

PMID- 28444182
TI  - Ventricular fibrillation triggered by a pacemaker-mediated tachycardia protection
      algorithm.

PMID- 28444181
TI  - Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.
AB  - Background: Impaired endogenous stem cell repair capacity is hypothesized to be a
      biologic basis of frailty. Therapies that restore regenerative capacity may
      therefore be beneficial. This Phase 1 study evaluated the safety and potential
      efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)
      based therapy in patients with aging frailty. Methods: In this nonrandomized,
      dose-escalation study, patients received a single intravenous infusion of allo
      hMSCs: 20-million (n = 5), 100-million (n = 5), or 200-million cells (n = 5). The
      primary endpoint was incidence of any treatment-emergent serious adverse events
      measured at 1 month postinfusion. The secondary endpoints were functional
      efficacy domains and inflammatory biomarkers, measured at 3 and 6 months,
      respectively. Results: There were no treatment-emergent serious adverse events at
      1-month postinfusion or significant donor-specific immune reactions during the
      first 6 months. There was one death at 258 days postinfusion in the 200-million
      group. In all treatment groups, 6-minute walk distance increased at 3 months (p =
      .02) and 6 months (p = .001) and TNF-alpha levels decreased at 6 months (p <
      .0001). Overall, the 100-million dose showed the best improvement in all
      parameters, with the exception of TNF-alpha, which showed an improvement in both
      the 100- and 200-million groups (p = .0001 and p = .0001, respectively). The 100
      million cell-dose group also showed significant improvements in the physical
      component of the SF-36 quality of life assessment at all time points relative to
      baseline. Conclusions: Allo-hMSCs are safe and immunologically tolerated in aging
      frailty patients. Improvements in functional and immunologic status suggest that
      ongoing clinical development of cell-based therapy is warranted for frailty.

PMID- 28444184
TI  - Can school-based distribution be used to maintain coverage of long-lasting
      insecticide treated bed nets: evidence from a large scale programme in southern
      Tanzania?
AB  - Many sub-Saharan African countries have achieved substantial gains in insecticide
      treated bednet coverage since 2005. The Tanzania National Malaria Control
      Programme identified school-based net distribution as one potential 'keep-up'
      strategy for the purpose of maintaining long-lasting insecticidal net (LLIN)
      coverage after a nationwide mass campaign in 2011. The School Net Programme (SNP)
      was implemented in three regions of southern Tanzania and distributed one LLIN to
      each enrolled child attending schools in primary grades (standards) 1, 3, 5 and
      7, and secondary grades (forms) 2 and 4 in 2013 and again with slightly modified
      eligibility criteria in 2014 and 2015. Household surveys in the programme area as
      well as in a control area were conducted after each of the SNP distributions to
      measure ownership and use of long-lasting insecticide treated nets. Ownership of
      at least one LLIN after the first distribution was 76.1% (95% CI 70.8-80.7) in
      the intervention area and 78.6% (95% CI 74.4-82.3) in the control area. After the
      second distribution, ownership of at least one LLIN had dropped significantly in
      the control area to 65.4% (95% CI 59.5-71.0) in 2015 (P < 0.001), while coverage
      in the intervention area was maintained at 79.3% (95% CI 75.4 * 82.6). Ownership
      of at least one LLIN in intervention area remained stable following the second
      round of net distribution. During the same period LLIN ownership, especially of
      enough nets to ensure all household member access, fell significantly in the
      control area. These results demonstrate that the SNP may be sufficient to
      maintain stable LLIN coverage following a mass distribution of LLINs.

PMID- 28444185
TI  - Layer-Dependent Short-Term Synaptic Plasticity Between Excitatory Neurons in the
      C2 Barrel Column of Mouse Primary Somatosensory Cortex.
AB  - Neurons process information through spatiotemporal integration of synaptic input.
      Synaptic transmission between any given pair of neurons is typically a dynamic
      process with presynaptic action potentials (APs) evoking depressing or
      facilitating postsynaptic potentials when presynaptic APs occur within hundreds
      of milliseconds of each other. In order to understand neocortical function, it is
      therefore important to investigate such short-term synaptic plasticity at
      synapses between different types of neocortical neurons. Here, we examine short
      term synaptic dynamics between excitatory neurons in different layers of the
      mouse C2 barrel column through in vitro whole-cell recordings. We find layer
      dependent short-term plasticity, with depression being dominant at many synaptic
      connections. Interestingly, however, presynaptic layer 2 neurons predominantly
      give rise to facilitating excitatory synaptic output at short interspike
      intervals of 10 and 30 ms. Previous studies have found prominent burst firing of
      excitatory neurons in supragranular layers of awake mice. The facilitation we
      observed in the synaptic output of layer 2 may, therefore, be functionally
      relevant, possibly serving to enhance the postsynaptic impact of burst firing.

PMID- 28444183
TI  - Calcium dysregulation and Cdk5-ATM pathway involved in a mouse model of fragile X
      associated tremor/ataxia syndrome.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder
      that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in
      FMR1, presenting with early alterations in neuronal network formation and
      function that precede neurodegeneration. Whether intranuclear inclusions
      containing DNA damage response (DDR) proteins are causally linked to abnormal
      synaptic function, neuronal growth and survival are unknown. In a mouse that
      harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP
      expression is moderately reduced from birth through adulthood, with greater FMRP
      reductions in the soma than in the neurite, despite several-fold elevation of
      Fmr1 mRNA levels. Resting cytoplasmic calcium concentration ([Ca2+]i) in cultured
      preCGG hippocampal neurons is chronically elevated, 3-fold compared to Wt;
      elevated ROS and abnormal glutamatergic responses are detected at 14 DIV.
      Elevated u-calpain activity and a higher p25/p35 ratio in the cortex of preCGG
      young adult mice indicate abnormal Cdk5 regulation. In support, the Cdk5
      substrate, ATM, is upregulated by 1.5- to 2-fold at P0 and 6 months in preCGG
      brain, as is p-Ser1981-ATM. Bax:Bcl-2 is 30% higher in preCGG brain, indicating a
      greater vulnerability to apoptotic activation. Elevated [Ca2+]i, ROS, and DDR
      signals are normalized with dantrolene. Chronic [Ca2+]i dysregulation amplifies
      Cdk5-ATM signaling, possibly linking impaired glutamatergic signaling and DDR to
      neurodegeneration in preCGG brain.

PMID- 28444186
TI  - Frataxin deficiency impairs mitochondrial biogenesis in cells, mice and humans.
AB  - Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by inherited
      deficiency of the mitochondrial protein Frataxin (FXN), which has no approved
      therapy and is an area in which biomarkers are needed for clinical development.
      Here, we investigated the consequences of FXN deficiency in patient-derived FRDA
      fibroblast cell models, the FRDA mouse model KIKO, and in whole blood collected
      from patients with FRDA. We observed decreased mitochondrial copy number in all
      the three FRDA models tested: cells, mice and patient blood. In addition, we
      observed 40% residual mitochondrial gene expression in FRDA patient blood. These
      deficiencies of mitochondrial biogenesis in FRDA cells and patient blood are
      significantly correlated with FXN expression, consistent with the idea that the
      decreased mitochondrial biogenesis is a consequence of FXN deficiency. The
      observations appear relevant to the FRDA pathophysiological mechanism, as FXN
      dependent deficiency in mitochondrial biogenesis and consequent mitochondrial
      bioenergetic defect could contribute to the neurodegenerative process. The
      observations may also have translational potential, as mitochondrial biogenesis
      could now be followed as a clinical biomarker of FRDA as a correlate of disease
      severity, progression, and therapeutic effect. Also, mitochondrial copy number in
      blood is objective, scalar and more investigator-independent than clinical
      neurological patient rating scales. Thus, FXN deficiency causes mitochondrial
      deficiency in FRDA cells, the KIKO mouse model, and in whole blood of patients
      with FRDA, and this deficiency could potentially be used in clinical trial
      design.

PMID- 28444187
TI  - Modelling the cost-effectiveness of PCSK9 inhibitors vs. ezetimibe through LDL-C
      reductions in a Norwegian setting.
AB  - Aims: Despite the success of statins, there remains unmet clinical need in
      cardiovascular disease (CVD) prevention. New proprotein convertase
      subtilisin/kexin type 9 (PCSK9) inhibitors reduce low-density lipoprotein
      cholesterol (LDL-C) by 55-65%. Two PCSK9 inhibitors, evolocumab, and alirocumab,
      were approved for use in Norway but not yet for reimbursement through public
      national insurance. We aim to explore the cost-effectiveness of these compared
      with available treatments in a Norwegian setting. Methods and results: A state
      transition Markov model was developed to model the cost-effectiveness of PCSK9
      inhibitors for prevention of coronary heart disease, ischaemic strokes, and death
      among high-risk patient subpopulations in Norway, in both primary and secondary
      settings. Evolocumab and alirocumab are compared against ezetimibe and standard
      treatment. Risk of CVD is based on population incidence rates and adjusted
      according to baseline risk factors. Preventative effect of treatment was modelled
      according to absolute reduction in LDL-C. PCSK9 inhibitors were never found to be
      cost-effective in primary prevention. In secondary prevention they were cost
      effective only for older, high-risk patients. The lowest cost-effectiveness
      ratios were for heterozygous familial hypercholesterolaemia patients and high
      risk diabetics, with ?63 200 and ?68 400 per quality-adjusted life-year,
      respectively. Conclusion: High lifetime costs of PCSK9 inhibitors may not be
      offset by estimated health gains for most eligible patients. PCSK9 inhibitors are
      found in the model only to be cost-effective in secondary prevention for older
      patients with high absolute risk of CVD. This picture is likely to change as
      price decreases. Future research is needed to determine the long-term
      preventative effects of PCSK9 inhibitors.

PMID- 28444188
TI  - Gas Chromatography-Mass Spectrometry Method to Quantify Benzo[a]Pyrene in Tobacco
      Products.
AB  - The USA Food and Drug Administration (FDA) established benzo[a]pyrene (B[a]P) as
      a harmful and potentially harmful constituent (HPHC) found in tobacco products.
      Tobacco manufacturers are required to report HPHC quantities to the FDA; however,
      there is currently no standardized method for determination of B[a]P in smokeless
      tobacco products (STPs). This work details a sensitive, selective and rapid
      method for the determination of B[a]P in STPs, cigarette filler and tobacco.
      Tobacco is extracted using methanol followed by solid-phase extraction and
      concentration prior to analysis by gas chromatography/mass spectrometry in the
      selected ion monitoring mode. Cooperation Centre for Scientific Research Relative
      to Tobacco reference products and 3R4F Kentucky reference cigarette filler were
      used for method validation. All method validation requirements were met including
      linearity, accuracy, precision, robustness, limit of detection (LOD) and limit of
      quantitation (LOQ), and stability. Calibration range of 0.5-125 ng mL-1 was
      achieved with the coefficient of determination (R2) greater than 0.995. The
      method LOQ and LOD were 0.729 and 0.216 ng/g, respectively. Using standardized
      methods for the measurement of HPHCs in tobacco products will reduce variability
      and ensure accurate data for regulatory reporting.

PMID- 28444189
TI  - Environmental Enrichment in the 21st Century.
AB  - More than a quarter of a century has elapsed since the Animal Welfare Act
      mandated that research facilities develop and follow a plan to promote the
      psychological well-being of captive primates. Since passage of this law,
      considerable effort and resources have been directed to designing environmental
      enrichment strategies in an effort to improve animal welfare. These plans
      typically consist of environmental enrichment and socialization efforts. While
      environmental enhancement has undergone a great deal of improvement in the past
      25 years, it should be viewed as a continual work in progress, which takes
      advantage of emergent and future technologies. In this review, we discuss the
      objectives of the environmental enhancement plan along with relevant outcome
      measures, as well as ongoing challenges, costs, and benefits. We then review
      various enrichment strategies and assess their efficacy in meeting goals and
      objectives. Finally, we look forward to consider what the future might hold for
      environmental enrichment of nonhuman primates used in research.

PMID- 28444190
TI  - Biological Aging and the Human Gut Microbiota.
AB  - The human gastrointestinal microbiota plays a key homeostatic role in normal
      functioning of physiologic processes commonly undermined by aging. We used a
      previously validated 34-item frailty index (FI34) to identify changes in gut
      microbiota community structure associated with biological age of community
      dwelling adults. Stool 16S rRNA cDNA libraries from 85 subjects ranging in age
      (43-79) and FI34 score (0-0.365) were deep sequenced, denoised, and clustered
      using DADA2. Subject biological age but not chronological age correlated with a
      decrease in stool microbial diversity. Specific microbial genera were
      differentially abundant in the lower, middle, and upper 33rd percentiles of
      biological age. Using Sparse Inverse Covariance Estimation for Ecological
      Association and Statistical Inference (SPIEC-EASI) and Weighted Gene Co
      Expression Network Analysis (WGCNA), we identified modules of coabundant
      microbial genera that distinguished biological from chronological aging. A
      biological age-associated module composed of Eggerthella, Ruminococcus, and
      Coprobacillus genera was robust to correction for subject age, sex, body mass
      index, antibiotic usage, and other confounders. Subject FI34 score positively
      correlated with the abundance of this module, which exhibited a distinct inferred
      metagenome as predicted by Phylogenetic Investigation of Communities by
      Reconstruction of Unobserved States (PICRUSt). We conclude that increasing
      biological age in community-dwelling adults is associated with gastrointestinal
      dysbiosis.

PMID- 28444191
TI  - Risks of miscarriage or preterm delivery in trichorionic and dichorionic triplet
      pregnancies with embryo reduction versus expectant management: a systematic
      review and meta-analysis.
AB  - STUDY QUESTION: Is pregnancy outcome in triplet pregnancies improved with embryo
      reduction (ER) to twins compared to expectant management? SUMMARY ANSWER: In
      trichorionic triplet pregnancies, ER to twins reduces the risk of preterm birth
      (<34 weeks) without significantly increasing the risk of miscarriage (<24 weeks),
      whereas in dichorionic triplet pregnancies, the results are inconclusive. WHAT IS
      KNOWN ALREADY: Triplet pregnancies are associated with a high risk of miscarriage
      and preterm birth. ER can ameliorate these conditions in higher order multiple
      gestations but is still controversial in triplets. STUDY DESIGN, SIZE, DURATION:
      This study aimed to conduct a systematic review, following the PRISMA guidelines,
      and critically appraise ER at 8-14 weeks of gestation in both trichorionic
      triamniotic (TCTA) and dichorionic triamniotic (DCTA) pregnancies. Selective ER
      to twins was compared with expectant management, focusing on the risks of
      miscarriage and preterm birth. The computerized database search was performed on
      8 January 2017. Overall, from 25 citations of relevance, eight studies with a
      total of 249 DCTA and 1167 TCTA pregnancies fulfilled the inclusion criteria.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A comprehensive computerized systematic
      literature search of all English language studies between 2000 and 2016 was
      performed in PubMed, EMBASE, Scopus, Evidence Based Medicine Reviews (Cochrane
      Database and Cochrane Central Register of Controlled Trials) and Google Scholar.
      Relevant article reference lists were hand searched. The management options were
      compared for rates of miscarriage <24 weeks and preterm birth <34 weeks. Only
      studies with both expectant management and ER to twins were included in the
      analysis. The quality of each individual article was critically appraised and
      appropriate statistical methods were used to extract results. MAIN RESULTS AND
      THE ROLE OF CHANCE: In TCTA pregnancies managed expectantly (n = 501), the rates
      of miscarriage and preterm birth were 7.4 and 50.2%, respectively. Meta-analysis
      demonstrated that ER to twins in TCTA pregnancies (n = 666) was associated with a
      lower risk (17.3 versus 50.2%) of preterm birth (RR = 0.36, 95% CI: 0.28-0.48),
      whereas the risk of miscarriage (8.1% versus 7.4%) did not significantly increase
      (RR = 1.08, 95% CI: 0.58-1.98). In DCTA triplets managed expectantly (n = 200),
      the rates of miscarriage and preterm birth were 8.5 and 51.9%, respectively.
      Although the meta-analysis was inconclusive, it suggested that ER to twins in
      DCTA triplets, either of the foetus with a separate placenta (n = 15) or one of
      the monochorionic pair (n = 34), was neither significantly associated with an
      increased risk of miscarriage (8.5 versus 13.3%, P = 0.628 and RR = 1.22, 95% CI:
      0.38-3.95, respectively) nor with a lower risk of preterm birth (51.9 versus
      46.2%, P = 0.778 and RR = 0.5, 95% CI: 0.04-5.7, respectively). LIMITATIONS,
      REASONS FOR CAUTION: No randomized controlled trials of ER versus expectant
      management in TCTA or DCTA pregnancies were identified from our literature
      search. We were able to include only a handful of papers with small sample sizes
      and suffering from bias, and non-English publications were missed. Irrespective
      of the strict inclusion and exclusion criteria, publication bias was evident.
      WIDER IMPLICATIONS OF THE FINDINGS: The greatest strength of our systematic
      review is that, contrary to the existing literature, it only included studies
      with both the intervention and expectant arm. Our results are in agreement with
      current literature. In TCTA pregnancies, ER to twins is associated with a lower
      risk of preterm birth but is not associated with a higher risk of miscarriage. In
      the absence of a randomized trial, the data from systematic reviews appear to be
      the best existing evidence for counselling in the first trimester on the
      different options available. Finally, in DCTA pregnancies, indications exist that
      ER (of one of the MC pair) to twins could possibly reduce the risk of preterm
      birth without increasing the risk of miscarriage. STUDY FUNDING/COMPETING
      INTEREST(S): None to declare. REGISTRATION NUMBER: N/A.

PMID- 28444192
TI  - From Reproducibility to Translation in Neurodegenerative Disease.
AB  - Despite tremendous investment and preclinical success in neurodegenerative
      disease, effective disease-altering treatments for patients have remained
      elusive. One highly cited reason for this discrepancy is flawed animal study
      design and reporting. If this can be broadly remedied, reproducibility of
      preclinical studies will improve. However, without concurrent efforts to improve
      generalizability, these improvements may not translate effectively from animal
      experiments to more complex human neurodegenerative diseases. Mechanistic and
      phenotypic variability of neurodegenerative disease is such that most models are
      only able to interrogate individual aspects of complex phenomena. One approach is
      to consider animals as models of individual targets rather than as models of
      individual diseases and to migrate the concept of predictive validity from the
      individual model to the body of experiments that demonstrate translatability of a
      target. Both exploratory and therapeutic preclinical studies are dependent upon
      study design methods that promote rigor and reproducibility. However, the body of
      evidence that is needed to demonstrate efficacy in therapeutic studies is
      substantially broader than that needed for exploratory studies. In addition to
      requiring rigor within individual experiments, convincing evidence for
      therapeutic potential must assess the relationships between model choice,
      intended goal of the intervention, pharmacologic criteria, and integration of
      biomarker data with outcome measures that are clinically relevant to humans. It
      is conceivable that proof-of-concept studies will migrate to cell-based systems
      and that animal systems will be increasingly reserved for more distal
      translational purposes. If this occurs, it is likely to prompt reexamination of
      what the term "translational" truly means.

PMID- 28444193
TI  - Quantitative assessment of timing, efficiency, specificity and genetic mosaicism
      of CRISPR/Cas9-mediated gene editing of hemoglobin beta gene in rhesus monkey
      embryos.
AB  - Gene editing technologies offer new options for developing novel biomedical
      research models and for gene and stem cell based therapies. However, applications
      in many species demand high efficiencies, specificity, and a thorough
      understanding of likely editing outcomes. To date, overall efficiencies, rates of
      off-targeting and degree of genetic mosaicism have not been well-characterized
      for most species, limiting our ability to optimize methods. As a model gene for
      measuring these parameters of the CRISPR/Cas9 application in a primate species
      (rhesus monkey), we selected the beta-hemoglobin gene (HBB), which also has high
      relevance to the potential application of gene editing and stem-cell technologies
      for treating human disease. Our data demonstrate an ability to achieve a high
      efficiency of gene editing in rhesus monkey zygotes, with no detected off-target
      effects at selected off-target loci. Considerable genetic mosaicism and variation
      in the fraction of embryonic cells bearing targeted alleles are observed, and the
      timing of editing events is revealed using a new model. The uses of Cas9-WT
      protein combined with optimized concentrations of sgRNAs are two likely areas for
      further refinement to enhance efficiency while limiting unfavorable outcomes that
      can be exceedingly costly for application of gene editing in primate species.

PMID- 28444195
TI  - DNA methylome analysis reveals distinct epigenetic patterns of ascending aortic
      dissection and bicuspid aortic valve.
AB  - Aims: Epigenetics may mediate the effects of environmental risk factors on
      disease, including heart disease. Thus, measuring the DNA methylome offers the
      opportunity to identify novel disease biomarkers and novel insights into disease
      mechanisms. The DNA methylation landscape of ascending aortic dissection (AD) and
      bicuspid aortic valve (BAV) with aortic aneurysmal dilatation remain
      uncharacterized. The present study aimed to explore the genome-wide DNA
      methylation landscape underpinning these two diseases. Methods and results: We
      used Illumina 450k DNA methylation beadarrays to analyse 21 ascending aorta
      samples, including 10 cases with AD, 5 with BAV and 6 healthy controls. We
      adjusted for intra-sample cellular heterogeneity, providing the first unbiased
      genome-wide exploration of the DNA methylation landscape underpinning these two
      diseases. We discover that both diseases are characterized by loss of DNA
      methylation at non-CpG sites. We validate this non-CpG hypomethylation signature
      with pyrosequencing. In contrast to non-CpGs, AD and BAV exhibit distinct DNA
      methylation landscapes at CpG sites, with BAV characterized mainly by
      hypermethylation of EZH2 targets. In the case of AD, integrative DNA methylation
      gene expression analysis reveals that AD is characterized by a dedifferentiated
      smooth muscle cell phenotype. Our integrative analysis further reveals
      hypomethylation associated overexpression of RARA in AD, a pattern which is also
      seen in cells exposed to smoke toxins. Conclusion: Our data supports a model in
      which increased cellular proliferation in AD and BAV underpins loss of
      methylation at non-CpG sites. Our data further supports a model, in which AD is
      associated with an inflammatory vascular remodeling process, possibly mediated by
      the epigenome and linked to environmental risk factors such as smoking.

PMID- 28444194
TI  - Evolution of the 3R-MYB Gene Family in Plants.
AB  - Plant 3R-MYB transcription factors are an important subgroup of the MYB super
      family in plants; however, their evolutionary history and functions remain poorly
      understood. We identified 225 3R-MYB proteins from 65 plant species, including
      algae and all major lineages of land plants. Two segmental duplication events
      preceding the common ancestor of angiosperms have given rise to three subgroups
      of the 3R-MYB proteins. Five conserved introns in the domain region of the 3R-MYB
      genes were identified, which arose through a step-wise pattern of intron gain
      during plant evolution. Alternative splicing (AS) analysis of selected species
      revealed that transcripts from more than 60% of 3R-MYB genes undergo AS. AS could
      regulate transcriptional activity for some of the plant 3R-MYBs by generating
      different regulatory motifs. The 3R-MYB genes of all subgroups appear to be
      enriched for Mitosis-Specific Activator (MSA) element core sequences within their
      upstream promoter region, which suggests a functional involvement in cell cycle.
      Notably, expression of 3R-MYB genes from different species exhibits differential
      regulation under various abiotic stresses. These data suggest that the plant 3R
      MYBs function in both cell cycle regulation and abiotic stress response, which
      may contribute to the adaptation of plants to a sessile lifestyle.

PMID- 28444196
TI  - Fluoroquinolone Use and Risk of Carpal Tunnel Syndrome: A Pharmacoepidemiologic
      Study.
AB  - Fluoroquinolone-induced peripheral neuropathies and tendinopathies are well
      documented, but there are no epidemiologic studies on the risk of carpal tunnel
      syndrome (CTS). We conducted a case-control study of >6 million patients.
      Fluoroquinolone use is associated with increased risk of CTS (rate ratio, 1.34
      [95% confidence interval, 1.31-1.37]).

PMID- 28444197
TI  - Understanding the linkages between social safety nets and childhood violence: a
      review of the evidence from low- and middle-income countries.
AB  - As many as one billion children experience violence every year, and household-
      and community-level poverty are among the risk factors for child protection
      violations. Social safety nets (SSNs) are a main policy tool to address poverty
      and vulnerability, and there is substantial evidence demonstrating positive
      effects on children's health and human capital. This paper reviews evidence and
      develops a framework to understand linkages between non-contributory SSNs and the
      experience of childhood emotional, physical and sexual violence in low- and
      middle-income countries. We catalogue 14 rigorous impact evaluations, 11 of which
      are completed, analysing 57 unique impacts on diverse violence indicators. Among
      these impacts, approximately one in five represent statistically significant
      protective effects on childhood violence. Promising evidence relates to sexual
      violence among female adolescents in Africa, while there is less clear evidence
      of significant impacts in other parts of the developing world, and on young child
      measures, including violent discipline. Further, few studies are set up to
      meaningfully unpack mechanisms between SSNs and childhood violence; however,
      those most commonly hypothesized operate at the household level (through
      increases in economic security and reductions in poverty-related stress), the
      interpersonal level (improved parental behaviours, caregiving practices, improved
      psychosocial well-being) and at the child-level (protective education and
      decreases in problem or risky behaviours). It is important to emphasize that
      traditional SSNs are never designed with violence prevention as primary
      objectives, and thus should not be considered as standalone interventions to
      reduce risks for childhood violence. However, SSNs, particularly within
      integrated protection systems, appear to have potential to reduce violence risk.
      Linkages between SSNs and childhood violence are understudied, and investments
      should be made to close this evidence gap.

PMID- 28444198
TI  - Isolation of the Lyme Disease Spirochete Borrelia mayonii From Naturally Infected
      Rodents in Minnesota.
AB  - Borrelia mayonii is a newly described member of the Borrelia burgdorferi sensu
      lato complex that is vectored by the black-legged tick (Ixodes scapularis Say)
      and a cause of Lyme disease in Minnesota and Wisconsin. Vertebrate reservoir
      hosts involved in the enzootic maintenance of B. mayonii have not yet been
      identified. Here, we describe the first isolation of B. mayonii from naturally
      infected white-footed mice (Peromyscus leucopus Rafinesque) and an American red
      squirrel (Tamiasciurus hudsonicus Erxleben) from Minnesota, thus implicating
      these species as potential reservoir hosts for this newly described spirochete.

PMID- 28444199
TI  - Geographical differences in prescription of secondary preventive drug therapy
      after acute myocardial infarction in Norway.

PMID- 28444201
TI  - Mitral periprosthetic leakage: contemporary results of surgical correction at a
      single centre.
AB  - OBJECTIVES: Mitral periprosthetic leakage (PPL) is a serious complication
      following valve replacement. Conflicting outcomes of surgical treatment have been
      reported in the presence of multiple previous cardiac operations and associated
      co-pathological conditions. METHODS: Sixty-five symptomatic patients (37 women,
      mean age 64.8 years) underwent conventional operations at our hospital from 2006
      to 2015. Mitral PPL was the leading surgical indication, although associated
      procedures were included. Previous transcatheter procedures and leaks involving
      multiple prostheses were excluded. The median number of past mitral operations
      was 2 (range 1-5). PPL recurrence was observed in 29% of cases. A previous
      operation on the aortic or tricuspid valve was performed in 31 patients. RESULTS:
      Mitral PPL involved one-, two- or three-quarters of the mitral perimeter in 46,
      43 and 11% of cases. Prosthetic refixation or replacement was performed in 24 and
      41 patients, respectively. Annular reconstruction was necessary in 17% of
      prosthetic replacements. Associated procedures were performed in 19 patients. The
      operation was executed through a right minithoracotomy (unclamped aorta) in 20%
      of patients. In-hospital deaths occurred in 3.1%. After a median follow-up of 60
      months, freedom from all-cause mortality was 96.8, 91.5 and 88.8% at 1, 3 and 5
      years. Lateral leaks [P = 0.03; hazard ratio (HR) = 4.57, 95% confidence interval
      (CI): 1.13-18.3] and PPL relapse (P = 0.03; HR = 4.33, 95% CI: 1.12-16.7) were
      independently associated with death. At follow-up, 4 patients had a >2+ recurrent
      leak and 2 were reoperated. CONCLUSIONS: A customized conventional mitral
      reoperation still represents a satisfactory and effective treatment option for
      PPL and should be considered even in patients with very complex issues.

PMID- 28444200
TI  - The Mediterranean: the cradle of Anthoxanthum (Poaceae) diploid diversity.
AB  - Background and Aims: Knowledge of diploid phylogeny and ecogeography provide a
      foundation for understanding plant evolutionary history, diversification patterns
      and taxonomy. The genus Anthoxanthum (vernal grasses, Poaceae) represents a
      taxonomically intricate polyploid complex with large phenotypic variation and
      poorly resolved evolutionary relationships. The aims of the study were to reveal:
      (1) evolutionary lineages of the diploid taxa and their genetic differentiation;
      (2) the past distribution of the rediscovered 'Mediterranean diploid'; and (3)
      possible migration routes of diploids in the Mediterranean. Methods: A combined
      approach involving sequencing of two plastid regions ( trnL-trnF and rpl32-trnL
      ), nrDNA ITS, rDNA FISH analyses, climatic niche characterization and spatio
      temporal modelling was used. Key Results: Among the examined diploid species,
      only two well-differentiated evolutionary lineages were recognized: Anthoxanthum
      gracile and A. alpinum . The other taxa - A. aristatum, A. ovatum, A. maderense
      and the 'Mediterranean diploid' - form a rather intermixed group based on the
      examined molecular data. In situ rDNA localization enabled identification of the
      ancestral Anthoxanthum karyotype, shared by A. gracile and two taxa from the
      crown group. For the studied taxa, ancestral location probabilities for six
      discrete geographical regions in the Mediterranean were proposed and likely
      scenarios of gradual expansion from them were suggested. Modelling past and
      present distributions shows that the 'Mediterranean diploid' has already been
      occurring in the same localities for 120 000 years. Conclusions: Highly congruent
      results were obtained and dated the origin and first diversification of
      Anthoxanthum to the Miocene. The later divergence probably took place in the
      Pleistocene and started polyploid evolution within the genus. The most recent
      diversification event is still occurring, and incomplete lineage sorting prevents
      full diversification of taxa at the molecular level, despite clear separation
      based on climatic niches. The 'Mediterranean diploid' is hypothesized to be a
      possible relic of the most recent common ancestor of Anthoxanthum due to their
      sharing of ancestral features.

PMID- 28444202
TI  - Application of Genomic Estimation Methods of Inbreeding and Population Structure
      in an Arabian Horse Herd.
AB  - Horse breeders rely heavily on pedigrees for identification of ancestry in
      breeding stock. Inaccurate pedigrees may erroneously assign individuals to false
      lineages or breed memberships resulting in wrong estimates of inbreeding and
      coancestry. Moreover, discrepancies in pedigree records can lead breeders seeking
      to limit inbreeding into making misguided breeding decisions. Genome-wide SNPs
      provide a quantitative tool to aid in the resolution of lineage assignments and
      the calculation of genomic measures of relatedness. The aim of this project was
      to pilot a comparison between pedigree and genomic relatedness and inbreeding
      measures in a herd of 36 pedigreed Egyptian Arabian horses genotyped using the
      Equine SNP70 platform (Geneseek, Inc.). Moreover, we sought to estimate the
      minimum number of markers sufficient for genomic inbreeding calculations.
      Pedigree inbreeding values were moderately correlated with genomic inbreeding
      values (r = 0.406), whereas genomic relationships and pedigree relationships have
      a high correlation (r = 0.77). Although first degree relationships were
      successfully reconstructed, more distant relationships were difficult to resolve.
      Multi-dimensional scaling and clustering analysis agreed with within-herd
      pedigree information. In comparing the herd to a reference sample of United
      States, Polish, and Egyptian Arabian horses, the herd's historically recorded
      Egyptian lineage was successfully recovered. We conclude that genomic estimates
      of inbreeding and relationships are superior to their pedigree counterparts. They
      can be thus utilized in conservation of valuable lines of livestock, and in
      breeds at risk for loss of genomic diversity. We also postulate a minimum of 2000
      markers in linkage equilibrium to be used for inbreeding estimation.

PMID- 28444203
TI  - A Chemosensory Protein Gene Si-CSP1 Associated With Necrophoric Behavior in Red
      Imported Fire Ants (Hymenoptera: Formicidae).
AB  - Necrophoric behavior is essential to colony health in social insects. Little is
      known about the genes that are responsible for necrophoric behavior. Here, we
      show that a chemosensory protein gene Si-CSP1 was expressed significantly higher
      in the antennae than in other tissues such as the legs and heads of Solenopsis
      invicta Buren workers. Furthermore, Si-CSP1-silenced workers moved significantly
      fewer corpses of their nestmates than normal workers. Finally, Si-CSP1-silenced
      workers exhibited weaker antennal responses to oleic acid and linoleic acid than
      controls. These results suggest that Si-CSP1 functions by sensing oleic acid and
      linoleic acid associated with dead colony members and regulating the necrophoric
      behavior of workers in S. invicta.

PMID- 28444205
TI  - Corrigendum.

PMID- 28444206
TI  - The Cost of Not Retesting: Human Immunodeficiency Virus Misdiagnosis in the
      Antiretroviral Therapy "Test-and-Offer" Era.
AB  - We compared estimated costs of retesting human immunodeficiency virus (HIV)
      positive persons before antiretroviral therapy (ART) initiation to the costs of
      ART provision to misdiagnosed HIV-negative persons. Savings from averted
      unnecessary ART costs were greater than retesting costs within 1 year using
      assumptions representative of HIV testing performance in programmatic settings.
      Countries should implement re-testing before ART initiation.

PMID- 28444207
TI  - Characterization of relative biological effectiveness for conventional radiation
      therapy: a comparison of clinical 6 MV X-rays and 137Cs.
AB  - Various types of radiation are utilized in the treatment of cancer. Equal
      physical doses of different radiation types do not always result in the same
      amount of biological damage. In order to account for these differences, a scaling
      factor known as the relative biological effectiveness (RBE) can be used.
      137Cesium (137Cs) has been used as a source of radiation in a significant body of
      radiation therapy research. However, high-energy X-rays, such as 6 MV X-rays, are
      currently used clinically to treat patients. To date, there is a gap in the
      literature regarding the RBE comparison of these two types of radiation.
      Therefore, the purpose of this study was to investigate the RBE of 137Cs relative
      to that of 6 MV X-rays. To determine the RBE, five cell lines were irradiated
      [Chinese hamster ovary (CHO); human lung adenocarcinoma (A549); human glioma
      (U251); human glioma (T98); and human osteosarcoma (U2OS)] by both types of
      radiation and assessed for cell survival using a clonogenic assay. Three of the
      five cell lines resulted in RBE values of ~1.00 to within 11% for all survival
      fractions, showing the physical and biological dose for these two types of
      radiation were equivalent. The other two cell lines gave RBE values differing
      from 1.00 by up to 36%. In conclusion, the results show the range in biological
      effect seen between cell lines, and therefore cell type must be considered when
      characterizing RBE.

PMID- 28444204
TI  - Murine Models of Sepsis and Trauma: Can We Bridge the Gap?
AB  - Sepsis and trauma are both leading causes of death in the United States and
      represent major public health challenges. Murine models have largely been used in
      sepsis and trauma research to better understand the pathophysiological changes
      that occur after an insult and to develop potential life-saving therapeutic
      agents. Mice are favorable subjects for this type of research given the variety
      of readily available strains including inbred, outbred, and transgenic strains.
      In addition, they are relatively easy to maintain and have a high fecundity.
      However, pharmacological therapies demonstrating promise in preclinical mouse
      models of sepsis and trauma often fail to demonstrate similar efficacy in human
      clinical trials, prompting considerable criticism surrounding the capacity of
      murine models to recapitulate complex human diseases like sepsis and traumatic
      injury. Fundamental differences between the two species include, but are not
      limited to, the divergence of the transcriptomic response, the mismatch of
      temporal response patterns, differences in both innate and adaptive immunity, and
      heterogeneity within the human population in comparison to the homogeneity of
      highly inbred mouse strains. Given the ongoing controversy, this narrative review
      aims to not only highlight the historical importance of the mouse as an animal
      research model but also highlight the current benefits and limitations of the
      model as it pertains to sepsis and trauma. Lastly, this review will propose
      future directions that may promote further use of the model.

PMID- 28444208
TI  - Adverse impacts of chronic pain on health-related quality of life, work
      productivity, depression and anxiety in a community-based study.
AB  - Background: Chronic pain has major clinical and social consequences. Few studies
      have examined any variation in the extent of impairment on quality of life and
      work productivity by site and type of chronic pain. Objective: The objective of
      our study is to examine adverse impacts of chronic pain on physical and
      psychological health and work productivity. Methods: Our community-population
      study was based on a phone-interview of adults with chronic pain, residing in
      Olmsted County, MN. Chronic pain groups were categorized into abdominal pain,
      back pain, joint pain, multisite pain, neuropathic pain or no chronic pain. We
      used standardized instruments, including the Brief Pain Inventory, the Patients
      Health Questionnair-9, and Work Productivity and Activity Impairment
      Questionnaire. Results: We evaluated 591 patients suffering from chronic pain and
      150 participants with no chronic pain. Almost one third of patients with
      multisite pain (33%) and neuropathic pain (32%) reported mild/major depressive
      symptoms. Patients suffering from chronic pain, particularly from multisite pain
      and neuropathic pain, reported significant pain interferences with daily
      activities and impairments in physical function. Chronic pain was significantly
      associated with reduced performance at work but not with missed work hours. The
      average reported reduction in work productivity ranged from 2.4 hours (+/-5.6)
      per week for adults with joint chronic pain to 9.8 hours (+/-11.1) per week for
      adults with multisite chronic pain. Conclusions: Chronic pain, particularly
      multisite pain and neuropathic pain, significantly affected physical and
      psychological health. Chronic pain is a multifaceted health condition that
      requires a multidisciplinary treatment approach.

PMID- 28444209
TI  - Variation in the Time of Colonization of Broiler Carcasses by Carrion Flies in
      Nakhonsawan Province, Thailand.
AB  - Carrion flies are the primary insects colonizing vertebrate carrion; however,
      limited information is available on the variation in the time of colonization
      (TOC) as related to time of placement (TOP) and time of death (TOD), particularly
      in Thailand. Three seasonal sets of nine broiler carcasses (euthanized and placed
      in field within 0.5 h after death) were placed in mesh enclosures within a
      disturbed deciduous dipterocarp forest at Nakhonsawan Province, upper-central
      Thailand, for 3 d to determine the colonization time by carrion flies. In total,
      21,536 arthropods were collected using traps placed over each carcass. Carrion
      flies of the family Calliphoridae, Muscidae, and Sarcophagidae predominated
      (93.42%). Of these, Chrysomya megacephala (F.) (Diptera: Calliphoridae) and
      Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) were the dominant
      species being 36.18% and 35.36%, respectively, across season. These species
      arrived immediately (5 min) after placement of the carrion in the field during
      the rainy season, while they were delayed 1-2 h during the dry season. Chrysomya
      megacephala, C. rufifacies, and Parasarcophaga dux (Thomson) colonized the
      remains. Time of colonization by C. megacephala and C. rufifacies occurred mostly
      at ~1600-1700 hours (10-11 h after placement) for all seasons. In contrast, TOC
      by P. dux was delayed for 1 d during rainy and dry season. These results mark the
      first record of carrion fly colonization in this area and also may deserve
      important information for the further study as they demonstrate time of
      colonization differs from TOP and most importantly TOD.

PMID- 28444210
TI  - Initial shunt type at the Norwood operation impacts myocardial function in
      hypoplastic left heart syndrome.
AB  - OBJECTIVES: We investigated the impact of initial shunt type, a Blalock-Taussig
      (BT) shunt versus a right ventricle to pulmonary artery conduit (RV-PA) on
      myocardial function at different stages of surgical palliation in patients with
      hypoplastic left heart syndrome (HLHS). METHODS: A population-based cohort of 63
      Finnish children with HLHS (BT n  = 23, RV-PA n  = 40) born between 2003 and 2010
      were studied retrospectively by echocardiography prior to Stages 1, 2 and 3
      palliation and 0.5-3 years after Stage 3. For comparison of systolic myocardial
      function, we evaluated the RV fractional area change (FAC), strain, strain rate
      and mechanical synchrony from the apical 4-chamber view by velocity vector
      imaging. RESULTS: There were no intergroup differences in demographics during the
      study period. At baseline, no intergroup differences were detected in RV systolic
      myocardial function. Before Stage 2, RV FAC was higher ( P  = 0.03) in the RV-PA
      conduit group. At Stage 3, an increase in all systolic myocardial functional
      parameters was observed in the BT shunt group. After Stage 3, the BT shunt group
      had better RV systolic function. In multiple regression analysis, the shunt type
      and the stage of palliation had an impact on myocardial function. CONCLUSIONS:
      Although patients with HLHS initially palliated with a BT shunt demonstrate lower
      RV FAC after Stage I, RV FAC improves after Stage 2 with better systolic
      performance after Stage 3 compared with those initially palliated with an RV-PA
      conduit.

PMID- 28444211
TI  - Effects of Sample Size and Full Sibs on Genetic Diversity Characterization: A
      Case Study of Three Syntopic Iberian Pond-Breeding Amphibians.
AB  - Accurate characterization of genetic diversity is essential for understanding
      population demography, predicting future trends and implementing efficient
      conservation policies. For that purpose, molecular markers are routinely
      developed for nonmodel species, but key questions regarding sampling design, such
      as calculation of minimum sample sizes or the effect of relatives in the sample,
      are often neglected. We used accumulation curves and sibship analyses to explore
      how these 2 factors affect marker performance in the characterization of genetic
      diversity. We illustrate this approach with the analysis of an empirical dataset
      including newly optimized microsatellite sets for 3 Iberian amphibian species:
      Hyla molleri, Epidalea calamita, and Pelophylax perezi. We studied 17-21
      populations per species (total n = 547, 652, and 516 individuals, respectively),
      including a reference locality in which the effect of sample size was explored
      using larger samples (77-96 individuals). As expected, FIS and tests for Hardy
      Weinberg equilibrium and linkage disequilibrium were affected by the presence of
      full sibs, and most initially inferred disequilibria were no longer statistically
      significant when full siblings were removed from the sample. We estimated that to
      obtain reliable estimates, the minimum sample size (potentially including full
      sibs) was close to 20 for expected heterozygosity, and between 50 and 80 for
      allelic richness. Our pilot study based on a reference population provided a
      rigorous assessment of marker properties and the effects of sample size and
      presence of full sibs in the sample. These examples illustrate the advantages of
      this approach to produce robust and reliable results for downstream analyses.

PMID- 28444212
TI  - Numerical Response and Impact of Laricobius nigrinus (Coleoptera: Derodontidae)
      on Adelges tsugae (Hemiptera: Adelgidae) in Their Native Range.
AB  - To determine if key attributes for a successful biological control agent are
      possessed by the predator, Laricobius nigrinus Fender, field studies were
      conducted in its native range of Seattle, WA. The relationship between adult and
      immature L. nigrinus abundance to different densities of its prey, Adelges tsugae
      Annand, were determined. In a second study, predator and prey densities, and
      survivorship of each sistens A. tsugae stage were determined to gauge the impact
      of predation. The predator strongly aggregated and increased its reproduction
      when prey density increased, the two mechanisms of a numerical response. Immature
      predator-prey ratios were high and average prey density was low in comparison
      with invaded areas of the eastern United States. Survivorship of aestivating
      first-instar sistens A. tsugae was low and survivorship of each instar (second,
      third, and fourth) and adults was high and increased with each stage. When
      pooled, however, the survivorship of sistens second instar-ovisac stages was low
      primarily owing to L. nigrinus larval consumption of ovisacs. In its native
      range, L. nigrinus has key attributes of a successful biological control agent,
      such as a strong numerical response, high predator-prey ratios, and an important
      larval impact on A. tsugae populations. Demographic data could serve as important
      benchmarks for future studies to determine if L. nigrinus and other predators can
      regulate densities of A. tsugae below eastern hemlock's physiological damage
      threshold in the eastern United States.

PMID- 28444213
TI  - Representation of occupational information across resources and validation of the
      occupational data for health model.
AB  - Reports by the National Academy of Medicine and leading public health
      organizations advocate including occupational information as part of an
      individual's social context. Given recent National Academy of Medicine
      recommendations on occupation-related data in the electronic health record, there
      is a critical need for improved representation. The National Institute for
      Occupational Safety and Health has developed an Occupational Data for Health
      (ODH) model, currently in draft format. This study aimed to validate the ODH
      model by mapping occupation-related elements from resources representing
      recommendations, standards, public health reports and surveys, and research
      measures, along with preliminary evaluation of associated value sets. All 247
      occupation-related items across 20 resources mapped to the ODH model. Recommended
      value sets had high variability across the evaluated resources. This study
      demonstrates the ODH model's value, the multifaceted nature of occupation
      information, and the critical need for occupation value sets to support clinical
      care, population health, and research.

PMID- 28444214
TI  - Can we afford not to screen for FH?

PMID- 28444215
TI  - Behavioral and Pharmacological Adherence in Pediatric Sickle Cell Disease: Parent
      Child Agreement and Family Factors Associated With Adherence.
AB  - Objective: This study aimed to evaluate agreement between children and parents on
      a measure of behavioral and pharmacological adherence in children with sickle
      cell disease (SCD), and the associations among family factors (i.e., problem
      solving skills, routines, communication) and adherence behaviors. Methods: In
      all, 85 children (aged 8-18 years) with SCD and their parents completed
      questionnaires assessing individual and family factors. Results: Overall parent
      child agreement on an adherence measure was poor, particularly for boys and older
      children. Greater use of child routines was associated with better overall child
      reported adherence. Open family communication was associated with higher overall
      parent-reported adherence. Conclusions: While further research is needed before
      definitive conclusions can be drawn, results suggest the need to assess child
      adherence behaviors via both child and parent reports. Findings also suggest that
      more daily family routines and open family communication may be protective
      factors for better disease management.

PMID- 28444216
TI  - Dietary metabolites derived from gut microbiota: critical modulators of
      epigenetic changes in mammals.
AB  - The mammalian gastrointestinal tract harbors trillions of commensal
      microorganisms, collectively known as the microbiota. The microbiota is a
      critical source of environmental stimuli and, thus, has a tremendous impact on
      the health of the host. The microbes within the microbiota regulate homeostasis
      within the gut, and any alteration in their composition can lead to disorders
      that include inflammatory bowel disease, allergy, autoimmune disease, diabetes,
      mental disorders, and cancer. Hence, restoration of the gut flora following
      changes or imbalance is imperative for the host. The low-molecular-weight
      compounds and nutrients such as short-chain fatty acids, polyamines, polyphenols,
      and vitamins produced by microbial metabolism of nondigestible food components in
      the gut actively participate in various epigenomic mechanisms that reprogram the
      genome by altering the transcriptional machinery of a cell in response to
      environmental stimuli. These epigenetic modifications are caused by a set of
      highly dynamic enzymes, notably histone acetylases, deacetylases, DNA methylases,
      and demethylases, that are influenced by microbial metabolites and other
      environmental cues. Recent studies have shown that host expression of histone
      acetylases and histone deacetylases is important for regulating communication
      between the intestinal microbiota and the host cells. Histone acetylases and
      deacetylases influence the molecular expression of genes that affect not only
      physiological functions but also behavioral shifts that occur via neuroepigenetic
      modifications of genes. The underlying molecular mechanisms, however, have yet to
      be fully elucidated and thus provide a new area of research. The present review
      provides insights into the current understanding of the microbiota and its
      association with mammalian epigenomics as well as the interaction of pathogens
      and probiotics with host epigenetic machinery.

PMID- 28444217
TI  - Direct and Indirect Effects of Pesticides on the Insidious Flower Bug (Hemiptera:
      Anthocoridae) Under Laboratory Conditions.
AB  - Greenhouse producers are interested in integrating natural enemies along with
      pesticides to suppress western flower thrips, Frankliniella occidentalis
      (Pergande), populations. The insidious flower bug, Orius insidiosus (Say), is a
      commercially available natural enemy of western flower thrips. We conducted a
      series of laboratory experiments to determine the direct and indirect effects of
      28 pesticides (insecticides, miticides, and fungicides), 4 pesticide mixtures,
      and 4 surfactants (36 total treatments plus a water control) on the adult O.
      insidiosus survival and predation on western flower thrips adults under
      laboratory conditions. The number of live and dead O. insidiosus adults was
      recorded after 24, 48, 72, and 96 h. The results of the study indicate that the
      fungicides (aluminum tris, azoxystrobin, fenhexamid, and kresoxim-methyl), insect
      growth regulators (azadirachtin, buprofezin, kinoprene, and pyriproxyfen),
      botanicals (Capsicum oleoresin extract, garlic oil, soybean oil; and rosemary,
      rosemary oil, peppermint oil, and cottonseed oil), and entomopathogenic fungi
      (Beauveria bassiana and Metarhizium anisopliae) were minimally directly harmful
      to adult O. insidiosus, with 80% to 100% adult survival. However, abamectin,
      spinosad, pyridalyl, chlorfenapyr, tau-fluvalinate, imidacloprid, dinotefuran,
      acetamiprid, and thiamethoxam directly affected O. insidiosus survival after 96 h
      (0-60% adult survival). The pesticide mixtures of abamectin + spinosad and
      chlorfenapyr + dinotefuran reduced adult survival (20% and 0%, respectively,
      after 48 h). Furthermore, the surfactants were not directly harmful to O.
      insidiosus adults. All western flower thrips adults were killed by the surviving
      adult O. insidiosus after 48 h, indicating no indirect effects of the pesticides
      on predation.

PMID- 28444218
TI  - Current Dilemmas in Defining the Boundaries of Disease.
AB  - Boorse's biostatistical theory states that diseases should be defined in ways
      that reflect disturbances of biological function and that are objective and value
      free. We use three examples from contemporary medicine that demonstrate the
      complex issues that arise when defining the boundaries of disease: polycystic
      ovary syndrome, chronic kidney disease, and myocardial infarction. We argue that
      the biostatistical theory fails to provide sufficient guidance on where the
      boundaries of disease should be drawn, contains ambiguities relating to choice of
      reference class, and is out of step with medical processes for identifying
      disease boundaries. Although proponents of the biostatistical theory might regard
      these practical issues as irrelevant to the aim of providing a theoretical
      account of disease, we take them to indicate the need for a theoretical account
      that is adequate for current needs-including limiting new forms of medicalization
      that are driven by the identification of disease based on dysfunction. Our
      processes for determining the boundaries for disease need to recognize that there
      is no value-free method for making these decisions.

PMID- 28444219
TI  - DNA methylation of a novel PAK4 locus influences ototoxicity susceptibility
      following cisplatin and radiation therapy for pediatric embryonal tumors.
AB  - Background: Ototoxicity is a common adverse side effect of platinum chemotherapy
      and cranial radiation therapy; however, individual susceptibility is highly
      variable. Therefore, our objective was to conduct an epigenome-wide association
      study to identify differentially methylated cytosine-phosphate-guanine (CpG)
      sites associated with ototoxicity susceptibility among cisplatin-treated
      pediatric patients with embryonal tumors. Methods: Samples were collected for a
      discovery cohort (n = 62) and a replication cohort (n = 18) of medulloblastoma
      and primitive neuroectodermal tumor patients. Posttreatment audiograms were
      evaluated using the International Society of Paediatric Oncology (SIOP) Boston
      Ototoxicity Scale. Genome-wide associations between CpG methylation and
      ototoxicity were examined using multiple linear regression, controlling for
      demographic and treatment factors. Results: The mean cumulative dose of cisplatin
      was 330 mg/m2 and the mean time from end of therapy to the last available
      audiogram was 6.9 years. In the discovery analysis of 435233 CpG sites, 6 sites
      were associated with ototoxicity grade (P < 5 * 10-5) after adjusting for
      confounders. Differential methylation at the top CpG site identified in the
      discovery cohort (cg14010619, PAK4 gene) was replicated (P = 0.029) and reached
      genome-wide significance (P = 2.73 * 10-8) in a combined analysis. These findings
      were robust to a sensitivity analysis evaluating other potential confounders.
      Conclusions: We identified and replicated a novel CpG methylation loci
      (cg14010619) associated with ototoxicity severity. Methylation at cg14010619 may
      modify PAK4 activity, which has been implicated in cisplatin resistance in
      malignant cell lines.

PMID- 28444221
TI  - Multicenter, open-label, extension trial to evaluate the long-term efficacy and
      safety of early versus delayed treatment with tolvaptan in autosomal dominant
      polycystic kidney disease: the TEMPO 4:4 Trial.

PMID- 28444222
TI  - FERONIA Receptor Kinase at the Crossroads of Hormone Signaling and Stress
      Responses.
AB  - Plant receptor-like kinases (RLKs) are involved in nearly all aspects of plant
      life including growth, development and stress response. Recent studies show that
      FERONIA (FER), a CrRLK1L subfamily member, is a versatile regulator of cell
      expansion and serves as a signaling node mediating cross-talk among multiple
      phytohormones. As a receptor for the RALF (Rapid Alkalinization Factor) peptide
      ligand, FER triggers a downstream signaling cascade that leads to a rapid
      cytoplasmic calcium increase and inhibition of cell elongation in plants.
      Moreover, FER recruits and activates small G proteins through the guanine
      nucleotide exchange factor-Rho-like GTPase (GEF-ROP) network to regulate both
      auxin and ABA responses that cross-talk with the RALF signaling pathway. One of
      the downstream processes is NADPH oxidase-dependent ROS (reactive oxygen species)
      production that modulates cell expansion and responses to both abiotic and biotic
      stress responses. Intriguingly, some pathogenic fungi produce RALF-like peptides
      to activate the host FER-mediated pathway and thus increase their virulence and
      cause plant disease. Studies so far indicate that FER may serve as a central node
      of the cell signaling network that integrates a number of regulatory pathways
      targeting cell expansion, energy metabolism and stress responses. This review
      focuses on recent findings and their implications in the context of FER action as
      a modulator that is crucial for hormone signaling and stress responses.

PMID- 28444220
TI  - A panel study on patients with dominant cerebellar ataxia highlights the
      frequency of channelopathies.
AB  - Autosomal dominant cerebellar ataxias have a marked heterogeneous genetic
      background, with mutations in 34 genes identified so far. This large amount of
      implicated genes accounts for heterogeneous clinical presentations, making
      genotype-phenotype correlations a major challenge in the field. While
      polyglutamine ataxias, linked to CAG repeat expansions in genes such as ATXN1,
      ATXN2, ATXN3, ATXN7, CACNA1A and TBP, have been extensively characterized in
      large cohorts, there is a need for comprehensive assessment of frequency and
      phenotype of more 'conventional' ataxias. After exclusion of CAG/polyglutamine
      expansions in spinocerebellar ataxia genes in 412 index cases with dominantly
      inherited cerebellar ataxias, we aimed to establish the relative frequencies of
      mutations in other genes, with an approach combining panel sequencing and
      TaqMan(r) polymerase chain reaction assay. We found relevant genetic variants in
      59 patients (14.3%). The most frequently mutated were channel genes [CACNA1A (n =
      16), KCND3 (n = 4), KCNC3 (n = 2) and KCNA1 (n = 2)]. Deletions in ITPR1 (n = 11)
      were followed by biallelic variants in SPG7 (n = 9). Variants in AFG3L2 (n = 7)
      came next in frequency, and variants were rarely found in STBN2 (n = 2), ELOVL5,
      FGF14, STUB1 and TTBK2 (n = 1 each). Interestingly, possible risk factor variants
      were detected in SPG7 and POLG. Clinical comparisons showed that ataxias due to
      channelopathies had a significantly earlier age at onset with an average of 24.6
      years, versus 40.9 years for polyglutamine expansion spinocerebellar ataxias and
      37.8 years for SPG7-related forms (P = 0.001). In contrast, disease duration was
      significantly longer in the former (20.5 years versus 9.3 and 13.7, P=0.001),
      though for similar functional stages, indicating slower progression of the
      disease. Of interest, intellectual deficiency was more frequent in channel
      spinocerebellar ataxias, while cognitive impairment in adulthood was similar
      among the three groups. Similar differences were found among a single gene group,
      comparing 23 patients with CACNA1A expansions (spinocerebellar ataxia 6) to 22
      patients with CACNA1A point mutations, which had lower average age at onset (25.2
      versus 47.3 years) with longer disease duration (18.7 versus 10.9), but lower
      severity indexes (0.39 versus 0.44), indicating slower progression of the
      disease. In conclusion, we identified relevant genetic variations in up to 15% of
      cases after exclusion of polyglutamine expansion spinocerebellar ataxias, and
      confirmed CACNA1A and SPG7 as major ataxia genes. We could delineate firm
      genotype-phenotype correlations that are important for genetic counselling and of
      possible prognostic value.

PMID- 28444223
TI  - Gene ORGANizer: linking genes to the organs they affect.
AB  - One of the biggest challenges in studying how genes work is understanding their
      effect on the physiology and anatomy of the body. Existing tools try to address
      this using indirect features, such as expression levels and biochemical pathways.
      Here, we present Gene ORGANizer (geneorganizer.huji.ac.il), a phenotype-based
      tool that directly links human genes to the body parts they affect. It is built
      upon an exhaustive curated database that links >7000 genes to ~150 anatomical
      parts using >150 000 gene-organ associations. The tool offers user-friendly
      platforms to analyze the anatomical effects of individual genes, and identify
      trends within groups of genes. We demonstrate how Gene ORGANizer can be used to
      make new discoveries, showing that chromosome X is enriched with genes affecting
      facial features, that positive selection targets genes with more constrained
      phenotypic effects, and more. We expect Gene ORGANizer to be useful in a variety
      of evolutionary, medical and molecular studies aimed at understanding the
      phenotypic effects of genes.

PMID- 28444225
TI  - Genetic Influence on the Sulcal Pits: On the Origin of the First Cortical Folds.
AB  - The influence of genes on cortical structures has been assessed through various
      phenotypes. The sulcal pits, which are the putative first cortical folds, have
      for long been assumed to be under tight genetic control, but this was never
      quantified. We estimated the pit depth heritability in various brain regions
      using the high quality and large sample size of the Human Connectome Project
      pedigree cohort. Analysis of additive genetic variance indicated that their
      heritability ranges between 0.2 and 0.5 and displays a regional genetic control
      with an overall symmetric pattern between hemispheres. However, a noticeable
      asymmetry of heritability estimates is observed in the superior temporal sulcus
      and could thus be related to language lateralization. The heritability range
      estimated in this study reinforces the idea that cortical shape is determined
      primarily by nongenetic factors, which is consistent with the important increase
      of cortical folding from birth to adult life and thus predominantly constrained
      by environmental factors. Nevertheless, the genetic cues, implicated with various
      local levels of heritability in the formation of sulcal pits, play a fundamental
      role in the normal gyral pattern development. Quantifying their influence and
      identifying the underlying genetic variants would provide insight into
      neurodevelopmental disorders.

PMID- 28444224
TI  - Pharmacodynamics of colistin and fosfomycin: a 'treasure trove' combination
      combats KPC-producing Klebsiella pneumoniae.
AB  - Objectives: KPC-producing Klebsiella pneumoniae are an emerging public health
      problem around the globe. We defined the combinatorial pharmacodynamics and
      ability to suppress resistance of two 'old' antibiotics, fosfomycin and colistin,
      in time-kill experiments and hollow-fibre infection models (HFIM). Methods: Two
      KPC-2-producing K. pneumoniae isolates were used: one susceptible to both
      colistin and fosfomycin (KPC 9A: MIC colistin 0.25 mg/L and MIC fosfomycin <=8
      mg/L) and the other resistant to colistin and susceptible to fosfomycin (KPC 5A:
      MIC colistin 64 mg/L and MIC fosfomycin 32 mg/L). Time-kill experiments assessed
      an array of colistin and fosfomycin concentrations against both isolates.
      Colistin and fosfomycin pharmacokinetics from critically ill patients were
      simulated in the HFIM to define the pharmacodynamic activity of humanized
      regimens over 5 days against KPC 9A. Results: In time-kill experiments, synergy
      was demonstrated for all colistin/fosfomycin combinations containing >8 mg/L
      fosfomycin against the double-susceptible KPC strain, 9A. Synergy versus KPC
      strain 5A was only achieved at the highest concentrations of colistin (4 mg/L)
      and fosfomycin (512 mg/L) at 48 h. In the HFIM, colistin or fosfomycin
      monotherapies resulted in rapid proliferation of resistant subpopulations; KPC 9A
      regrew by 24 h. In contrast to the monotherapies, the colistin/fosfomycin
      combination resulted in a rapid 6.15 log 10  cfu/mL reduction of KPC 9A by 6 h
      and complete suppression of resistant subpopulations until 120 h. Conclusions:
      Colistin and fosfomycin may represent an important treatment option for KPC
      producing K. pneumoniae otherwise resistant to traditional antibiotics.

PMID- 28444226
TI  - Evaluation of a Live Attenuated Human Metapneumovirus Vaccine in Adults and
      Children.
AB  - We conducted a phase I clinical trial of an experimental live attenuated
      recombinant human metapneumovirus (HMPV) vaccine (rHMPV-Pa) sequentially in
      adults, HMPV-seropositive children, and HMPV-seronegative children, the target
      population for vaccination. rHMPV-Pa was appropriately restricted in replication
      in adults and HMPV-seropositive children but was overattenuated for HMPV
      seronegative children.

PMID- 28444227
TI  - Incidence and prognosis of patients with brain metastases at diagnosis of
      systemic malignancy: a population-based study.
AB  - Background: Brain metastases are associated with significant morbidity and
      mortality. Population-level data describing the incidence and prognosis of
      patients with brain metastases are lacking. The aim of this study was to
      characterize the incidence and prognosis of patients with brain metastases at
      diagnosis of systemic malignancy using recently released data from the
      Surveillance, Epidemiology, and End Results (SEER) program. Methods: We
      identified 1302166 patients with diagnoses of nonhematologic malignancies
      originating outside of the CNS between 2010 and 2013 and described the incidence
      proportion and survival of patients with brain metastases. Results: We identified
      26430 patients with brain metastases at diagnosis of cancer. Patients with small
      cell and non-small cell lung cancer displayed the highest rates of identified
      brain metastases at diagnosis; among patients presenting with metastatic disease,
      patients with melanoma (28.2%), lung adenocarcinoma (26.8%), non-small cell lung
      cancer not otherwise specified/other lung cancer (25.6%), small cell lung cancer
      (23.5%), squamous cell carcinoma of the lung (15.9%), bronchioloalveolar
      carcinoma (15.5%), and renal cancer (10.8%) had an incidence proportion of
      identified brain metastases of >10%. Patients with brain metastases secondary to
      prostate cancer, bronchioloalveolar carcinoma, and breast cancer displayed the
      longest median survival (12.0, 10.0, and 10.0 months, respectively). Conclusions:
      In this study we provide generalizable estimates of the incidence and prognosis
      for patients with brain metastases at diagnosis of a systemic malignancy. These
      data may allow for appropriate utilization of brain-directed imaging as screening
      for subpopulations with cancer and have implications for clinical trial design
      and counseling of patients regarding prognosis.

PMID- 28444228
TI  - Improved outcome and cost effectiveness in ablation of persistent atrial
      fibrillation under general anaesthetic.
AB  - Aims: Outcome of persistent atrial fibrillation (AF) ablation remains suboptimal.
      Techniques employed to reduce arrhythmia recurrence rate are more likely to be
      embraced if cost-effectiveness can be demonstrated. A single-centre observational
      study assessed whether use of general anaesthesia (GA) in persistent AF ablation
      improved outcome and was cost-effective. Methods and results: Two hundred and
      ninety two patients undergoing first ablation procedures for persistent AF under
      conscious sedation or GA were followed. End points were freedom from listing for
      repeat ablation at 18 months and freedom from recurrence of atrial arrhythmia at
      1 year. Freedom from atrial arrhythmia was higher in patients who underwent
      ablation under GA rather than sedation (63.9% vs. 42.3%, hazard ratio (HR) 1.87,
      95% confidence interval (CI): 1.23-2.86, P = 0.002). Significantly fewer GA
      patients were listed for repeat procedures (29.2% vs. 42.7%, HR 1.62, 95% CI:
      1.01-2.60, P = 0.044). Despite GA procedures costing slightly more, a saving of
      L177 can be made per patient in our centre for a maximum of two procedures if all
      persistent AF ablations are performed under GA. Conclusions: In patients with
      persistent AF, it is both clinical and economically more effective to perform
      ablation under GA rather than sedation.

PMID- 28444229
TI  - A novel but frequent variant in LPA KIV-2 is associated with a pronounced Lp(a)
      and cardiovascular risk reduction.
AB  - Aims: Lp(a) concentrations represent a major cardiovascular risk factor and are
      almost entirely controlled by one single locus (LPA). However, many genetic
      factors in LPA governing the enormous variance of Lp(a) levels are still unknown.
      Since up to 70% of the LPA coding sequence are located in a difficult to access
      hypervariable copy number variation named KIV-2, we hypothesized that it may
      contain novel functional variants with pronounced effects on Lp(a)
      concentrations. We performed a large scale mutation analysis in the KIV-2 using
      an extreme phenotype approach. Methods and Results: We compiled an discovery set
      of 123 samples showing discordance between LPA isoform phenotype and Lp(a)
      concentrations and controls. Using ultra-deep sequencing, we identified a splice
      site variant (G4925A) in preferential association with the smaller LPA isoforms.
      Follow-up in a European general population (n = 2892) revealed an exceptionally
      high carrier frequency of 22.1% in the general population. The variant explains
      20.6% of the Lp(a) variance in carriers of low molecular weight (LMW) apo(a)
      isoforms (P = 5.75e-38) and reduces Lp(a) concentrations by 31.3 mg/dL.
      Accordingly the odds ratio for cardiovascular disease was reduced from 1.39 [95%
      confidence interval (CI): 1.17-1.66, P = 1.89e-04] for wildtype LMW individuals
      to 1.19 [95%CI: 0.92; 1.56, P = 0.19] in LMW individuals who were additionally
      positive for G4925A. Functional studies point towards a reduction of splicing
      efficiency by this novel variant. Conclusion: A highly frequent but until now
      undetected variant in the LPA KIV-2 region is strongly associated with reduced
      Lp(a) concentrations and reduced cardiovascular risk in LMW individuals.

PMID- 28444230
TI  - APOE epsilon4/epsilon4 diminishes neurotrophic function of human iPSC-derived
      astrocytes.
AB  - The epsilon4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong
      genetic risk factor for aging-related cognitive decline as well as late-onset
      Alzheimer's disease (AD) compared to the common epsilon3 allele. In the central
      nervous system, apoE is produced primarily by astrocytes and functions in
      transporting lipids including cholesterol to support neuronal homeostasis and
      synaptic integrity. Although mouse models and corresponding primary cells have
      provided valuable tools for studying apoE isoform-dependent functions, recent
      studies have shown that human astrocytes have a distinct gene expression profile
      compare with rodent astrocytes. Human induced pluripotent stem cells (iPSCs)
      derived from individuals carrying specific gene variants or mutations provide an
      alternative cellular model more relevant to humans upon differentiation into
      specific cell types. Thus, we reprogramed human skin fibroblasts from cognitively
      normal individuals carrying APOE epsilon3/epsilon3 or epsilon4/epsilon4 genotype
      to iPSC clones and further differentiated them into neural progenitor cells and
      then astrocytes. We found that human iPSC-derived astrocytes secreted abundant
      apoE with apoE4 lipoprotein particles less lipidated compared to apoE3 particles.
      More importantly, human iPSC-derived astrocytes were capable of promoting
      neuronal survival and synaptogenesis when co-cultured with iPSC-derived neurons
      with APOE epsilon4/epsilon4 astrocytes less effective in supporting these
      neurotrophic functions than those with APOE epsilon3/epsilon3 genotype. Taken
      together, our findings demonstrate APOE genotype-dependent effects using human
      iPSC-derived astrocytes and provide novel evidence that the human iPSC-based
      model system is a strong tool to explore how apoE isoforms contribute to
      neurodegenerative diseases.

PMID- 28444231
TI  - Whole-Genome Sequencing of Seven Strains of Staphylococcus lugdunensis Allows
      Identification of Mobile Genetic Elements.
AB  - Coagulase negative staphylococci are normal inhabitant of the human skin flora
      that account for an increasing number of infections, particularly hospital
      acquired infections. Staphylococcus lugdunensis has emerged as a most virulent
      species causing various infections with clinical characteristics close to what
      clinicians usually observe with Staphylococcus aureus and both bacteria share
      more than 70% of their genome. Virulence of S. aureus relies on a large
      repertoire of virulence factors, many of which are encoded on mobile genetic
      elements. S. lugdunensis also bears various putative virulence genes but only one
      complete genome with extensive analysis has been published with one prophage
      sequence (phiSL2) and a unique plasmid was previously described. In this study,
      we performed de novo sequencing, whole genome assembly and annotation of seven
      strains of S. lugdunensis from VISLISI clinical trial. We searched for the
      presence of virulence genes and mobile genetics elements using bioinformatics
      tools. We identified four new prophages, named phiSL2 to phiSL4, belonging to the
      Siphoviridae class and five plasmids, named pVISLISI_1 to pVISLISI_5. Three
      plasmids are homologous to known plasmids that include, amongst others, one S.
      aureus plasmid. The two other plasmids were not described previously. This study
      provides a new context for the study of S. lugdunensis virulence suggesting the
      occurrence of several genetic recombination' with other staphylococci.

PMID- 28444233
TI  - Neighborhood Variation in the Price of Cheap Tobacco Products in California:
      Results From Healthy Stores for a Healthy Community.
AB  - Background: Retail marketing surveillance research highlights concerns about
      lower priced cigarettes in neighborhoods with a higher proportion of
      racial/ethnic minorities but focuses almost exclusively on premium brands. To
      remedy this gap in the literature, the current study examines neighborhood
      variation in prices for the cheapest cigarettes and a popular brand of cigarillos
      in a large statewide sample of licensed tobacco retailers in a low-tax state.
      Methods: All 61 local health departments in California trained data collectors to
      conduct observations in a census of eligible licensed tobacco retailers in
      randomly selected zip codes (n = 7393 stores, completion rate=91%). Data were
      collected in 2013, when California had a low and stagnant tobacco tax. Two prices
      were requested: the cheapest cigarette pack regardless of brand and a single,
      flavored Swisher Sweets cigarillo. Multilevel models (stores clustered in tracts)
      examined prices (before sales tax) as a function of neighborhood race/ethnicity
      and proportion of school-age youth (aged 5-17). Models adjusted for store type
      and median household income. Results: Approximately 84% of stores sold cigarettes
      for less than $5 and a Swisher Sweets cigarillo was available for less than $1 in
      74% of stores that sold the brand. The cheapest cigarettes cost even less in
      neighborhoods with a higher proportion of school-age residents and Asian/Pacific
      Islanders. Conclusions: Neighborhood disparities in the price of the cheapest
      combustible tobacco products are a public health threat. Policy changes that make
      all tobacco products, especially combustible products, less available and more
      costly may reduce disparities in their use and protect public health.
      Implications: Much of what is known about neighborhood variation in the price of
      combustible tobacco products focuses on premium brand cigarettes. The current
      study extends this literature in two ways, by studying prices for the cheapest
      cigarette pack regardless of brand and a popular brand of flavored cigarillos and
      by reporting data from the largest statewide sample of licensed tobacco
      retailers. Significantly lower prices in neighborhoods with a higher proportion
      of youth and of racial/ethnic groups with higher smoking prevalence are a cause
      of concern. The study results underscore the need for policies that reduce
      availability and increase price of combustible tobacco products, particularly in
      states with low, stagnant tobacco taxes.

PMID- 28444234
TI  - Inferring Allele Frequency Trajectories from Ancient DNA Indicates That Selection
      on a Chicken Gene Coincided with Changes in Medieval Husbandry Practices.
AB  - Ancient DNA provides an opportunity to infer the drivers of natural selection by
      linking allele frequency changes to temporal shifts in environment or cultural
      practices. However, analyses have often been hampered by uneven sampling and
      uncertainties in sample dating, as well as being confounded by demographic
      processes. Here, we present a Bayesian statistical framework for quantifying the
      timing and strength of selection using ancient DNA that explicitly addresses
      these challenges. We applied this method to time series data for two loci: TSHR
      and BCDO2, both hypothesised to have undergone strong and recent selection in
      domestic chickens. The derived variant in TSHR, associated with reduced
      aggression to conspecifics and faster onset of egg laying, shows strong selection
      beginning around 1,100 years ago, coincident with archaeological evidence for
      intensified chicken production and documented changes in egg and chicken
      consumption. To our knowledge, this is the first example of preindustrial
      domesticate trait selection in response to a historically attested cultural shift
      in food preference. For BCDO2, we find support for selection, but demonstrate
      that the recent rise in allele frequency could also have been driven by gene flow
      from imported Asian chickens during more recent breed formations. Our findings
      highlight that traits found ubiquitously in modern domestic species may not
      necessarily have originated during the early stages of domestication. In
      addition, our results demonstrate the importance of precise estimation of allele
      frequency trajectories through time for understanding the drivers of selection.

PMID- 28444232
TI  - Co-trimoxazole Prophylaxis, Asymptomatic Malaria Parasitemia, and Infectious
      Morbidity in Human Immunodeficiency Virus-Exposed, Uninfected Infants in Malawi:
      The BAN Study.
AB  - Background: Human immunodeficiency virus (HIV)-exposed infants are
      disproportionately at risk of morbidity and mortality compared with their HIV
      unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in
      reducing leading causes of infectious morbidity is unclear. Methods: We used data
      from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial
      (conducted 2004-2010, Malawi) to assess the association of (1) CPT and (2)
      asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in
      infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240
      mg) from 6 to 36 weeks of age, or until weaning occurred and HIV infection was
      ruled out. All HIV-exposed, uninfected infants (HEIs) at 8 weeks of age (n =
      1984) were included when CPT was the exposure. A subset of HEIs (n = 471) were
      tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks
      of age. Cox proportional hazards models for recurrent gap-time data were used to
      examine the association of time-varying exposures on morbidity. Results: CPT was
      associated with a 36% reduction in respiratory morbidity (hazard ratio [HR], 0.64
      [95% confidence interval {CI}, .60-.69]) and a 41% reduction in diarrheal
      morbidity (HR, 0.59 [95% CI, .54-.65]). Having asymptomatic malaria parasitemia
      was associated with a 40% increase in respiratory morbidity (HR, 1.40 [95% CI,
      1.13-1.74]) and a 50% increase in diarrheal morbidity (HR, 1.50 [95% CI, 1.09
      2.06]), after adjusting for CPT. Conclusions: CPT may have an important role to
      play in reducing the leading global causes of morbidity and mortality in the
      growing population of HEIs in malaria-endemic resource-limited settings.

PMID- 28444236
TI  - The cost of Lyme borreliosis.
AB  - Background: Lyme borreliosis (LB) is the most frequently reported tick-borne
      infection in Europe and North America. The aim of this study was to estimate the
      cost-of-illness of LB in the Netherlands. We used available incidence estimates
      from 2010 for tick bite consultations and three symptomatic LB outcomes: erythema
      migrans (EM), disseminated LB and Lyme-related persisting symptoms. The cost was
      estimated using these incidences and the average cost per patient as derived from
      a patient questionnaire. We estimated the cost from a societal perspective,
      including healthcare cost, patient cost and production loss, using the friction
      cost method and a 4% annual discount rate. Tick bites and LB in 2010 led to a
      societal cost of ?19.3 million (95% CI 15.6-23.4; 16.6 million population) for
      the Netherlands. Healthcare cost and production loss each constituted 48% of the
      total cost (?9.3 and ?9.2 million/year), and patient cost 4% (?0.8 million/year).
      Of the total cost, 37% was related to disseminated LB, followed by 27% for
      persisting symptoms, 22% for tick bites and 14% for EM. Per outcome, for an
      individual case the mean cost of disseminated LB and Lyme-related persisting
      symptoms was both around ?5700; for EM and GP consultations for tick bites this
      was ?122 and ?53. As an alternative to the friction cost method, the human
      capital method resulted in a total cost of ?23.5 million/year. LB leads to a
      substantial societal cost. Further research should therefore focus on additional
      preventive interventions.

PMID- 28444235
TI  - Right hemisphere structural adaptation and changing language skills years after
      left hemisphere stroke.
AB  - Stroke survivors with acquired language deficits are commonly thought to reach a
      'plateau' within a year of stroke onset, after which their residual language
      skills will remain stable. Nevertheless, there have been reports of patients who
      appear to recover over years. Here, we analysed longitudinal change in 28 left
      hemisphere stroke patients, each more than a year post-stroke when first assessed
      testing each patient's spoken object naming skills and acquiring structural brain
      scans twice. Some of the patients appeared to improve over time while others
      declined; both directions of change were associated with, and predictable given,
      structural adaptation in the intact right hemisphere of the brain. Contrary to
      the prevailing view that these patients' language skills are stable, these
      results imply that real change continues over years. The strongest brain
      behaviour associations (the 'peak clusters') were in the anterior temporal lobe
      and the precentral gyrus. Using functional magnetic resonance imaging, we
      confirmed that both regions are actively involved when neurologically normal
      control subjects name visually presented objects, but neither appeared to be
      involved when the same participants used a finger press to make semantic
      association decisions on the same stimuli. This suggests that these regions serve
      word-retrieval or articulatory functions in the undamaged brain. We teased these
      interpretations apart by reference to change in other tasks. Consistent with the
      claim that the real change is occurring here, change in spoken object naming was
      correlated with change in two other similar tasks, spoken action naming and
      written object naming, each of which was independently associated with structural
      adaptation in similar (overlapping) right hemisphere regions. Change in written
      object naming, which requires word-retrieval but not articulation, was also
      significantly more correlated with both (i) change in spoken object naming; and
      (ii) structural adaptation in the two peak clusters, than was change in another
      task-auditory word repetition-which requires articulation but not word retrieval.
      This suggests that the changes in spoken object naming reflected variation at the
      level of word-retrieval processes. Surprisingly, given their qualitatively
      similar activation profiles, hypertrophy in the anterior temporal region was
      associated with improving behaviour, while hypertrophy in the precentral gyrus
      was associated with declining behaviour. We predict that either or both of these
      regions might be fruitful targets for neural stimulation studies (suppressing the
      precentral region and/or enhancing the anterior temporal region), aiming to
      encourage recovery or arrest decline even years after stroke occurs.

PMID- 28444237
TI  - Janeway lesions.

PMID- 28444238
TI  - High-purity circular RNA isolation method (RPAD) reveals vast collection of
      intronic circRNAs.
AB  - High-throughput RNA sequencing methods coupled with specialized bioinformatic
      analyses have recently uncovered tens of thousands of unique circular (circ)RNAs,
      but their complete sequences, genes of origin and functions are largely unknown.
      Given that circRNAs lack free ends and are thus relatively stable, their
      association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence
      gene expression programs. While exoribonuclease treatment is widely used to
      degrade linear RNAs and enrich circRNAs in RNA samples, it does not efficiently
      eliminate all linear RNAs. Here, we describe a novel method for the isolation of
      highly pure circRNA populations involving RNase R treatment followed by
      Polyadenylation and poly(A)+ RNA Depletion (RPAD), which removes linear RNA to
      near completion. High-throughput sequencing of RNA prepared using RPAD from human
      cervical carcinoma HeLa cells and mouse C2C12 myoblasts led to two surprising
      discoveries: (i) many exonic circRNA (EcircRNA) isoforms share an identical
      backsplice sequence but have different body sizes and sequences, and (ii)
      thousands of novel intronic circular RNAs (IcircRNAs) are expressed in cells. In
      sum, isolating high-purity circRNAs using the RPAD method can enable quantitative
      and qualitative analyses of circRNA types and sequence composition, paving the
      way for the elucidation of circRNA functions.

PMID- 28444240
TI  - Nonspecific Effects of Oral Polio Vaccine on Diarrheal Burden and Etiology Among
      Bangladeshi Infants.
AB  - Background: As the global polio eradication initiative prepares to cease use of
      oral polio vaccine (OPV) in 2020, there is increasing interest in understanding
      if oral vaccination provides non-specific immunity to other infections so that
      the consequences of this transition can be effectively planned for and mitigated.
      Methods: Data were collected from infants in an urban slum in Bangladesh (Mirpur,
      Dhaka) as part of the performance of rotavirus and oral polio vaccines in
      developing countries (PROVIDE) study. Following vaccination with trivalent oral
      polio vaccine (tOPV) at 6, 10, and 14 weeks, infants were randomly assigned to
      receive tOPV (n = 315) or inactivated polio vaccine (IPV) (n = 299) at 39 weeks.
      Episodes of diarrhea were documented through clinic visits and twice-weekly house
      visits through 52 weeks. In sum, 14 pathogens associated with diarrhea were
      analyzed with TaqMan Array Cards. Results: Although the proportion of children
      experiencing diarrhea was not different between the tOPV and IPV groups (P =
      .18), the number of days with diarrhea (P = .0037) and the number of separate
      diarrheal episodes (P = .054) trended lower in the OPV arm. Etiological analysis
      revealed that male tOPV recipients were less likely to have diarrhea of bacterial
      etiology (P = .0099) compared to male IPV recipients but equally likely to
      experience diarrhea due to viruses (P = .57) or protozoa (P = .14). Among the 6
      bacterial enteric pathogens tested, only Campylobacter jejuni/coli detection was
      significantly reduced in the OPV arm (P = .0048). Conclusions: Our results
      suggest that OPV may cause nonspecific reductions in mortality, as has been
      studied elsewhere, by reducing etiology-specific diarrheal burden. This is likely
      driven by reductions in bacterial diarrhea. Further study of nonspecific OPV
      effects before global cessation is supported. Clinical Trials Registration:
      NCT01375647.

PMID- 28444239
TI  - The Influence of Social Conditions Across the Life Course on the Human Gut
      Microbiota: A Pilot Project With the Wisconsin Longitudinal Study.
AB  - Objective: To test the feasibility of collecting and integrating data on the gut
      microbiome into one of the most comprehensive longitudinal studies of aging and
      health, the Wisconsin Longitudinal Study (WLS). The long-term goal of this
      integration is to clarify the contribution of social conditions in shaping the
      composition of the gut microbiota late in life. Research on the microbiome, which
      is considered to be of parallel importance to human health as the human genome,
      has been hindered by human studies with nonrandomly selected samples and with
      limited data on social conditions over the life course. Methods: No existing
      population-based longitudinal study had collected fecal specimens. Consequently,
      we created an in-person protocol to collect stool specimens from a subgroup of
      WLS participants. Results: We collected 429 stool specimens, yielding a 74%
      response rate and one of the largest human samples to date. Discussion: The
      addition of data on the gut microbiome to the WLS-and to other population based
      longitudinal studies of aging-is feasible, under the right conditions, and can
      generate innovative research on the relationship between social conditions and
      the gut microbiome.

PMID- 28444241
TI  - Cervical Spine Muscle-Tendon Unit Length Differences Between Neutral and Forward
      Head Postures: Biomechanical Study Using Human Cadaveric Specimens.
AB  - Background: Forward head posture (FHP) may be associated with neck pain and poor
      health-related quality of life. Literature describes only qualitative muscle
      length changes associated with FHP. Objective: The purpose of this study was to
      quantify how muscle-tendon unit lengths are altered when human cadaveric
      specimens are placed in alignments representing different severities of FHP.
      Design: This biomechanical study used 13 fresh-frozen cadaveric cervical spine
      specimens (Occiput-T1, 54+/-15 y). Methods: Specimens' postural changes
      simulating increasing FHP severity while maintaining horizontal gaze were
      assessed. Specimen-specific anatomic models derived from computed tomography
      based anatomic data were combined with postural data and specimen-specific
      anatomy of muscle attachment points to estimate the muscle length changes
      associated with FHP. Results: Forward head posture was associated with flexion of
      the mid-lower cervical spine and extension of the upper cervical (sub-occipital)
      spine. Muscles that insert on the cervical spine and function as flexors (termed
      "cervical flexors") as well as muscles that insert on the cranium and function as
      extensors ("occipital extensors") shortened in FHP when compared to neutral
      posture. In contrast, muscles that insert on the cervical spine and function as
      extensors ("cervical extensors") as well as muscles that insert on the cranium
      and function as flexors ("occipital flexors") lengthened. The greatest shortening
      was seen in the major and minor rectus capitis posterior muscles. These muscles
      cross the Occiput-C2 segments, which exhibited extension to maintain horizontal
      gaze. The greatest lengthening was seen in posterior muscles crossing the C4-C6
      segments, which exhibited the most flexion. Limitations: This cadaver study did
      not incorporate the biomechanical influence of active musculature. Conclusions:
      This study offers a novel way to quantify postural alignment and muscle length
      changes associated with FHP. Model predictions are consistent with qualitative
      descriptions in the literature.

PMID- 28444242
TI  - Virulence and antimicrobial resistance of Salmonella spp. and Escherichia coli in
      the beef jerky production line.
AB  - Intense manipulation during beef jerky production increases the possibility of
      contamination with pathogenic microorganisms. This study evaluated the
      contamination by thermotolerant coliforms, Escherichia coli and Salmonella spp.,
      on processing surfaces and raw materials during beef jerky production, as well as
      in the final product. Thermotolerant coliforms were found on all surfaces tested
      and in the raw material. Escherichia coli was identified in 6.7% of the surface
      samples, while Salmonella spp. was found in 3.3% of the surface samples and 8.6%
      of raw material samples. Virulence genes were detected in Salmonella spp.
      isolates. One Salmonella spp. isolate was resistant to sulfonamide, while one E.
      coli isolate was multiresistant, including the presence of resistance genes sul2,
      strA, strB, tetA and tetB. The presence of coliforms demonstrates failings in
      hygienic-sanitary procedures. The presence of pathogenic microorganisms causing
      foodborne diseases in the production line indicates persistent contamination in
      the production plant. Although the drying process applied to beef jerky should
      guarantee the safety of the final product, the presence of multiresistant
      pathogenic microorganisms, presenting virulence genes, should be a matter of
      concern. Because beef jerky is a ready-to-eat product, a failure in the
      production process may cause such microorganisms to pose a public health risk.

PMID- 28444243
TI  - Sexual Activity and Relationship Quality in Middle and Older Age: Findings From
      The Irish Longitudinal Study on Ageing (TILDA).
AB  - Objectives: This study assessed the association between sexual activity,
      mismatches in the importance attributed to sex within couples, and relationship
      quality in older Irish adults. Method: We used data from the Irish Longitudinal
      Study on Ageing (TILDA) to derive a scale of subjective relationship strain in
      married or cohabiting individuals. Negative binomial regression was used to
      assess the association between relationship strain and sexual activity. Separate
      models assessed the associations with importance of sex and within-couple
      mismatch in the importance attributed to sex and whether these associations were
      independent from sexual activity. Age interactions were tested. Results: Sexual
      activity and within-couple mismatch in the importance attributed to sex were
      associated with relationship strain. The frequency of sexual activity was
      consistently associated with less relationship strain for men, but less so for
      women when the importance attributed to sex was accounted for. Results were
      largely consistent across age groups for men, but sexual activity and importance
      of sex varied with age in women. Discussion: Frequent sexual activity was
      associated with less strain within-intimate relationships. For women, this
      association was weakened when accounting for the importance attributed to sex.
      Within-couple mismatch in the importance attributed to sex was associated with
      relationship strain, independent from frequency of sexual activity, for both men
      and women at all ages.

PMID- 28444244
TI  - Cochrane Review Identifies Safe and Effective Treatment for Z-Joint Pain.

PMID- 28444245
TI  - Can a Community of Practice Improve Physical Therapists' Self-Perceived Practice
      in Developmental Coordination Disorder?
AB  - Background: Communities of practice (CoPs) are useful knowledge translation (KT)
      strategies, but little is known about their impact on physical therapists' self
      perceived practice. Purpose: The impact of a CoP on physical therapists' self
      perceived practice was evaluated, and factors influencing changes in self
      perceived knowledge, skills, and practice related to developmental coordination
      disorder (DCD) were explored. Design: An explanatory sequential mixed-methods
      design was used, guided by the Theory of Reasoned Action and Theory of Planned
      Behavior. Methods: Physical therapists participated in a DCD physical therapist
      CoP, which included 2 full-day, face-to-face workshops, with access to a 5-month
      online forum between the workshops, and completed questionnaires at 3 time
      points: before the first workshop, before accessing the online forum, and
      following the second workshop. Measures completed before and after the CoP
      included closed-ended questions providing global scores on therapists' self
      perceived knowledge, skills, and practice. Physical therapists' sociodemographic
      characteristics, information-seeking style, use of the online forum, and
      behavioral change goals were also collected. Paired t-tests, ANCOVAs, and linear
      regression models were used to analyze the data. Results: Forty-one physical
      therapists completed all questionnaires. Their self-perceived knowledge, skills,
      and practice change scores were significantly higher (+0.47, +1.23, and +2.61,
      respectively; P < .001) at the end of the CoP compared with the beginning. Few of
      the factors explored significantly influenced therapists' self-reported change
      scores. Limitations: No observational data on practice change was collected. The
      small sample may have limited the ability to identify factors influencing self
      perceived practice changes. Conclusions: The CoP increased physical therapists'
      self-perceived knowledge, skills, and practice. More research is needed to
      explore CoP impact on physical therapist practices and how behavioral changes
      influence patient outcomes.

PMID- 28444247
TI  - EXPOSURE PARAMETERS OF MAMMOGRAMS WITH AND WITHOUT MASS LESIONS FROM A SOUTH
      AFRICAN BREAST CARE CENTRE.
AB  - In South African breast care centres, full-field digital mammography units
      provide breast imaging services to symptomatic and asymptomatic women
      simultaneously. This study evaluated the technical exposure parameters of 800
      mammograms of which 100 mammograms had obvious mass lesions in the fibroglandular
      tissue. The average breast compression force of mammograms with mass lesions in
      the fibroglandular tissue was 18.4% less than the average breast compression
      force of mammograms without mass lesions. The average mean glandular dose (MGD),
      tube potential (kVp) and compressed breast thickness (CBT) values were 2.14 mGy,
      30.5 kVp and 63.9 mm, respectively, for mammograms with mass lesions, and 1.45
      mGy, 29.6 kVp and 56.9 mm, respectively, for mammograms without mass lesions.
      Overall, the average MGD and mean CBT of mammograms with mass lesion were
      significantly higher compared to those without mass lesions (p < 0.05), although
      there was no significant difference in their tube potentials (p > 0.05).

PMID- 28444246
TI  - Lateral Orbitofrontal Cortical Modulation on the Medial Prefrontal Cortex
      Amygdala Pathway: Differential Regulation of Intra-Amygdala GABAA and GABAB
      Receptors.
AB  - Background: The basolateral complex of the amygdala receives inputs from
      neocortical areas, including the medial prefrontal cortex and lateral
      orbitofrontal cortex. Earlier studies have shown that lateral orbitofrontal
      cortex activation exerts an inhibitory gating on medial prefrontal cortex
      amygdala information flow. Here we examined the individual role of GABAA and
      GABAB receptors in this process. Methods: In vivo extracellular single-unit
      recordings were done in anesthetized rats. We searched amygdala neurons that fire
      in response to medial prefrontal cortex activation, tested lateral orbitofrontal
      cortex gating at different delays (lateral orbitofrontal cortex-medial prefrontal
      cortex delays: 25, 50, 100, 250, 500, and 1000 milliseconds), and examined
      differential contribution of GABAA and GABAB receptors with iontophoresis.
      Results: Relative to baseline, lateral orbitofrontal cortex stimulation exerted
      an inhibitory modulatory gating on the medial prefrontal cortex-amygdala pathway
      and was effective up to a long delay of 500 ms (long-delay latencies at 100, 250,
      and 500 milliseconds). Moreover, blockade of intra-amygdala GABAA receptors with
      bicuculline abolished the lateral orbitofrontal cortex inhibitory gating at both
      short- (25 milliseconds) and long-delay (100 milliseconds) intervals, while
      blockade of GABAB receptors with saclofen reversed the inhibitory gating at long
      delay (100 milliseconds) only. Among the majority of the neurons examined (8 of
      9), inactivation of either GABAA or GABAB receptors during baseline did not
      change evoked probability per se, suggesting that local feed-forward inhibitory
      mechanism is pathway specific. Conclusions: Our results suggest that the effect
      of lateral orbitofrontal cortex inhibitory modulatory gating was effective up to
      500 milliseconds and that intra-amygdala GABAA and GABAB receptors differentially
      modulate the short- and long-delay lateral orbitofrontal cortex inhibitory gating
      on the medial prefrontal cortex-amygdala pathway.

PMID- 28444248
TI  - Effects of various spacers between biotin and the phospholipid headgroup on
      immobilization and sedimentation of biotinylated phospholipid-containing
      liposomes facilitated by avidin-biotin interactions.
AB  - Immobilization and sedimentation of liposomes (lipid vesicles) are used in
      liposome-protein binding assays, facilitated by avidin/streptavidin/NeutrAvidin
      and biotinylated phospholipid-containing liposomes. Here, we examined the effects
      of three spacers [six-carbon (X), polyethylene glycol (PEG) 180 (molecular weight
      180) and PEG2000 (molecular weight 2,000)] between biotin and the phospholipid
      headgroup on the immobilization and sedimentation of small unilamellar
      liposomes/vesicles (SUVs). PEG180 and PEG2000 showed more efficient
      immobilization of biotinylated SUVs on NeutrAvidin-coated plates than X, but X
      and PEG180 showed more efficient sedimentation of biotinylated SUVs upon
      NeutrAvidin addition than PEG2000. Thus, the most appropriate spacers differed
      between immobilization and sedimentation. A spacer for biotinylated SUVs must be
      selected according to the particular liposome-protein binding assays examined.

PMID- 28444250
TI  - Comment on the editorial by Turner et al. on assessment of cardiovascular risk of
      new drugs for the treatment of diabetes mellitus: risk assessment vs. risk
      aversion by Zannad et al.

PMID- 28444249
TI  - Quantitative analysis of the 3D cell shape changes driving soybean germination.
AB  - Seed germination is central to plant establishment and is the starting point for
      the majority of world agriculture. This transition from seed to seedling has been
      extensively studied at an organ level, while few studies have examined the
      cellular events which underlie it. Reports in the model species Arabidopsis have
      identified a radicle-derived wave of cell expansion underlying the germination
      process. Whether this spatiotemporal pattern of cell expansion is specific to
      this model plant or conserved in other species remains unknown. Here we examined
      the 3D cell anisotropy driving germination in soybean. By examining changes in
      cell shape at two positions along the length of the axis over time, preferential
      growth was observed in the portion of the axis closest to the radicle. A gradient
      of cell size was observed across the cortical cell layers of the soybean axis,
      and differences in starting cell size translated into differential relative
      growth rates across cell layers where larger cells showed greater relative growth
      rates than smaller cells. Differences in cell position-specific cell anisotropy
      were also observed. These data demonstrate that a radicle-derived growth pattern
      is present in the crop species soybean, and reveal the presence of a complex
      cellular organization in this hypocotyl which show cell type-specific anisotropy
      diving germination.

PMID- 28444251
TI  - Effect of EU electrical stunning conditions on breast meat quality of broiler
      chickens.
AB  - Electrical stunning is still the main stunning method used worldwide in
      commercial poultry plants. The stunning procedures in water bath stunners affect
      both bird welfare and meat quality attributes. The European Union (EU) Council
      Regulation 1099/2009 on the protection of the animal at the time of killing
      established the minimum current flow through an individual bird at a specified
      frequency to assure an effective stun that must last until the bird's death. The
      aim of this study was to compare the effect of the application of different
      stunning current flows on the prevalence of hemorrhages (classified as 1 = no
      lesion, 2 = moderate, and 3 = severe lesion) and some quality traits (pHu, color,
      drip and cooking losses, and shear force) of chicken breast meat. A total of 12
      flocks of broiler chickens, each equally divided into light, medium, and heavy
      sizes, was submitted either to the stunning condition usually adopted before the
      entry into force of the current EU regulation (90 mA/bird, 400 Hz) (OLD) or to
      that enforced by it (150 mA/bird, 400 Hz) (NEW). Overall, the prevalence of
      severe hemorrhages dramatically increased in the NEW group in comparison with the
      OLD one (55 vs. 27%; P < 0.001) and particularly in heavy-sized birds (72 vs.
      25%; P < 0.001). In general, meat quality attributes were not affected by the
      stunning conditions with the exception of drip loss that resulted lower in NEW
      than OLD birds (1.01 vs. 1.27; P < 0.001). In conclusion, the adoption of a
      higher current flow, as suggested by the EU regulation to protect animals at the
      time of killing, increases the prevalence of breast hemorrhages while maintaining
      meat quality traits with a possible beneficial effect on water holding capacity
      of fresh meat.

PMID- 28444252
TI  - Accurate Measurement of Indoor Radon Concentration using a Low-Effective Volume
      Radon Monitor.
AB  - AlphaGUARD is a low-effective volume detector and one of the most popular
      portable radon monitors which is currently available. This study investigated
      whether AlphaGUARD can accurately measure the variable indoor radon levels. The
      consistency of the radon-concentration data obtained by AlphaGUARD is evaluated
      against simultaneous measurements by two other monitors (each ~10 times more
      sensitive than AlphaGUARD). When accurately measuring radon concentration with
      AlphaGUARD, we found that the net counts of the AlphaGUARD were required of at
      least 500 counts, <25% of the relative percent difference. AlphaGUARD can provide
      accurate measurements of radon concentration for the world average level (~50 Bq
      m-3) and the reference level of workplace (1000 Bq m-3), using integrated data
      over at least 3 h and 10 min, respectively.

PMID- 28444253
TI  - Fear of Falling in People With Multiple Sclerosis: Which Clinical Characteristics
      Are Important?
AB  - Background: Fear of falling (FOF) is an important risk indicator for health
      related outcomes and quality of life in patients with multiple sclerosis (MS).
      However, factors associated with FOF in MS are not well investigated. Objectives:
      This study was done to explore predictors of FOF in this population. Methods:
      Seventy relapsing remitting patients with MS were evaluated. Fear of falling was
      assessed using the Fall Efficacy Scale-International (FES-I). Motor outcomes
      included: 30-second chair stand test (30s-CST), Berg Balance Scale (BBS), 10
      Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT). Cognitive status was
      determined using the Montreal Cognitive Assessment (MOCA) and Symbol Digit
      Modalities Test (SDMT). Affective factors including depression, fatigue, and
      sleep were also assessed using the Beck Depression Inventory (BDI), Modified
      Fatigue Impact Scale (MFIS), and Pittsburgh Sleep Quality Index (PSQI),
      respectively. Results: Fear of falling was significantly correlated with all
      motor and affective measures used. However, a stepwise regression found that only
      BBS from motor measures, MOCA from cognitive measures, and sleep disorders from
      affective factors were significantly predictive of the FOF. Conclusions: Fear of
      falling in patients with MS is multifactorial and includes motor and nonmotor
      factors. Thus, therapies that aim to reduce risk of falling in this population
      should address motor functions, cognitive abilities, and sleep quality.

PMID- 28444254
TI  - The Effect of Biosimilars [Inflectra(r)] in the Management of Acute Severe
      Ulcerative Colitis.

PMID- 28444256
TI  - Outcomes after the Mustard, Senning and arterial switch operation for treatment
      of transposition of the great arteries in Finland: a nationwide 4-decade
      perspective.
AB  - OBJECTIVES: We analysed nationwide early and late results after the Mustard,
      Senning and arterial switch operation. METHODS: We included all paediatric
      patients (<18 years) who underwent a Senning, a Mustard or an arterial switch
      operation for transposition of the great arteries from 1968 to 2009 in Finland.
      Data were obtained retrospectively from a paediatric cardiac surgical database
      and population data from the Finnish national registry. RESULTS: Early mortality
      (<30 days) was 11% after Mustard and 5% after Senning operation, while the rate
      decreased from 19% during 1976-1999 to 2% during 2000-2009 for arterial switch
      patients (P < 0.0001). The 43-year survival rate was 75% [95% confidence interval
      (CI) 70-80%] for all patients and 97% (95% CI 94-98%) for the general population.
      Late survival improved during later eras, with a 10-year survival of 96% (95% CI
      92-99%) for those operated during 2000-2009 vs 81% (95% CI 74-88%) in the 1990s
      (hazard ratio 3.7, 95% CI 1.4-9.6, P = 0.008). Twenty-year survival rates
      (without 30-day mortality) after arterial switch operation, Mustard and Senning
      were 97% (95% CI 95-100%), 78% (95% CI 68-87%) and 84% (95% CI 77-90%),
      respectively. No late sudden deaths or fatal heart failures occurred after the
      arterial switch operation. CONCLUSIONS: Outcome after surgery for transposition
      of the great arteries has improved, mostly due to the arterial switch operation
      but also due to improvements in perioperative care and follow-up. Operative
      deaths after the arterial switch operation have diminished, and no late sudden
      deaths or fatal heart failures occurred during the first 25-30 years after the
      procedure.

PMID- 28444257
TI  - ARTAIDSAMERICA: An Exhibit.

PMID- 28444255
TI  - Effect of cranial irradiation on sperm concentration of adult survivors of
      childhood acute lymphoblastic leukemia: a report from the St. Jude Lifetime
      Cohort Study?.
AB  - STUDY QUESTION: Does lower dose (<26 Gy) cranial radiation therapy (CRT) used for
      central nervous system prophylaxis in acute lymphoblastic leukemia (ALL)
      adversely affect sperm concentration or morphology? SUMMARY ANSWER: CRT doses <26
      Gy had no demonstrable adverse effect on sperm concentration or morphology. WHAT
      IS KNOWN ALREADY: Treatment with alkylating agents produces oligospermia and
      azoospermia in some patients. No prior study has been large enough to evaluate
      the independent effects of alkylating agents and lower dose (<26 Gy) CRT on sperm
      concentration or morphology. STUDY DESIGN, SIZE, DURATION: This cross-sectional
      study included male adult survivors of pediatric ALL who had received alkylating
      agent chemotherapy with or without CRT and who enrolled in the St. Jude Lifetime
      Cohort Study (SJLIFE) from September 2007 to October 2013.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The inclusion criteria were males, >=18
      years of age, >=10 years after diagnosis, treated at St. Jude Children's Research
      Hospital for ALL, and received alkylating agent chemotherapy. Semen analyses were
      performed on 173 of the 241 (78.1%) adult survivors of pediatric ALL who had
      received alkylating agent chemotherapy with or without CRT. Cumulative alkylating
      agent treatment was quantified using the cyclophosphamide equivalent dose (CED).
      Log-binomial multivariable models were used to calculate relative risks (RRs) and
      95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to those without CRT, risk
      of oligospermia or azoospermia was not increased for CRT <20 Gy (P = 0.95) or 20
      26 Gy (P = 0.58). Participants 5-9 years of age at diagnosis compared to those 0
      4 years of age (RR = 1.30, 95% CI, 1.05-.61) or those treated with 8-12 g/m2 CED
      (RR = 2.06, 95% CI, 1.08-3.94) or >=12 g/m2 CED (RR = 2.12, 95% CI, 1.09-4.12)
      compared to those treated with >0 to <4 g/m2 CED had an increased risk for
      oligospermia or azoospermia. LIMITATIONS, REASONS FOR CAUTION: Our study relied
      on the results of one semen analysis. ALL survivors who did not participate in
      SJLIFE or who declined to submit a semen analysis may also have biased our
      results regarding the proportion with azoospermia or oligospermia, since those
      who provided a semen specimen were less likely to have previously fathered
      children compared to those who did not. The lower rate of previous parenthood
      among participants may have resulted in a higher observed frequency of
      azoospermia and oligospermia. WIDER IMPLICATIONS OF THE FINDINGS: Treatment with
      <26 Gy CRT did not increase the risk of oligospermia or azoospermia, although a
      CED exceeding 8 g/m2 and an age at diagnosis of 5-9 years did increase risk of
      oligospermia and azoospermia. These findings can be used to counsel adult
      survivors of pediatric ALL. STUDY FUNDING/COMPETING INTEREST(S): This work was
      supported by the National Institutes of Health (grant numbers CA 21765, CA
      195547, CA00874) and the American Lebanese Syrian Associated Charities (ALSAC).
      The authors have no competing interests to declare.

PMID- 28444258
TI  - Errors in Data Analysis.

PMID- 28444259
TI  - Screening for Preeclampsia and the USPSTF Recommendations.

PMID- 28444260
TI  - Follow-up of Positive Fecal Test Results: Sooner Is Better, but How Much Better?

PMID- 28444262
TI  - Epidemic Tracking Tool Wins Open Science Prize.

PMID- 28444261
TI  - Mechanical Nasal Dilators to Treat Nasal Valve Compromise.

PMID- 28444263
TI  - National Academies Report Cites Flaws in VA's Burn Pit Registry.

PMID- 28444264
TI  - NIH Consortium to Study Biomarkers for Dementia.

PMID- 28444266
TI  - The Placebo Effect in Psychotherapy.

PMID- 28444267
TI  - Immunogenicity of 2 vs 3 Doses of the Quadrivalent Human Papillomavirus Vaccine
      in Girls Aged 9 to 13 Years After 60 Months.

PMID- 28444268
TI  - Estimating the Prevalence of Sexual Minority Adolescents.

PMID- 28444269
TI  - Urban-Rural Differences in Diabetes in China.

PMID- 28444270
TI  - Evolocumab Added to Statins to Reduce Progression of Coronary Atherosclerosis.

PMID- 28444271
TI  - Evolocumab Added to Statins to Reduce Progression of Coronary Atherosclerosis.

PMID- 28444272
TI  - Estimating the Prevalence of Sexual Minority Adolescents-Reply.

PMID- 28444273
TI  - Urban-Rural Differences in Diabetes-Associated Mortality in China-Reply.

PMID- 28444274
TI  - Evolocumab Added to Statins to Reduce Progression of Coronary Atherosclerosis
      Reply.

PMID- 28444276
TI  - Low-Intensity Weight-Maintenance Program Keeps Pounds Off.

PMID- 28444275
TI  - Bariatric Surgery Has Durable Effects in Controlling Diabetes.

PMID- 28444277
TI  - Acupuncture May Be Effective for Long-term Migraine Prophylaxis.

PMID- 28444278
TI  - Association Between Time to Colonoscopy After a Positive Fecal Test Result and
      Risk of Colorectal Cancer and Cancer Stage at Diagnosis.
AB  - Importance: The fecal immunochemical test (FIT) is commonly used for colorectal
      cancer screening and positive test results require follow-up colonoscopy.
      However, follow-up intervals vary, which may result in neoplastic progression.
      Objective: To evaluate time to colonoscopy after a positive FIT result and its
      association with risk of colorectal cancer and advanced-stage disease at
      diagnosis. Design, Setting, and Participants: Retrospective cohort study (January
      1, 2010-December 31, 2014) within Kaiser Permanente Northern and Southern
      California. Participants were 70 124 patients aged 50 through 70 years eligible
      for colorectal cancer screening with a positive FIT result who had a follow-up
      colonoscopy. Exposures: Time (days) to colonoscopy after a positive FIT result.
      Main Outcomes and Measures: Risk of any colorectal cancer and advanced-stage
      disease (defined as stage III and IV cancer). Odds ratios (ORs) and 95% CIs were
      adjusted for patient demographics and baseline risk factors. Results: Of the 70
      124 patients with positive FIT results (median age, 61 years [IQR, 55-67 years];
      men, 52.7%), there were 2191 cases of any colorectal cancer and 601 cases of
      advanced-stage disease diagnosed. Compared with colonoscopy follow-up within 8 to
      30 days (n = 27 176), there were no significant differences between follow-up at
      2 months (n = 24 644), 3 months (n = 8666), 4 to 6 months (n = 5251), or 7 to 9
      months (n = 1335) for risk of any colorectal cancer (cases per 1000 patients: 8
      30 days, 30; 2 months, 28; 3 months, 31; 4-6 months, 31; and 7-9 months, 43) or
      advanced-stage disease (cases per 1000 patients: 8-30 days, 8; 2 months, 7; 3
      months, 7; 4-6 months, 9; and 7-9 months, 13). Risks were significantly higher
      for examinations at 10 to 12 months (n = 748) for any colorectal cancer (OR, 1.48
      [95% CI, 1.05-2.08]; 49 cases per 1000 patients) and advanced-stage disease (OR,
      1.97 [95% CI, 1.14-3.42]; 19 cases per 1000 patients) and more than 12 months (n
      = 747) for any colorectal cancer (OR, 2.25 [95% CI, 1.89-2.68]; 76 cases per 1000
      patients) and advanced-stage disease (OR, 3.22 [95% CI, 2.44-4.25]; 31 cases per
      1000 patients). Conclusions and Relevance: Among patients with a positive fecal
      immunochemical test result, compared with follow-up colonoscopy at 8 to 30 days,
      follow-up after 10 months was associated with a higher risk of colorectal cancer
      and more advanced-stage disease at the time of diagnosis. Further research is
      needed to assess whether this relationship is causal.

PMID- 28444279
TI  - Trends in Infective Endocarditis in California and New York State, 1998-2013.
AB  - Importance: Prophylaxis and treatment guidelines for infective endocarditis have
      changed substantially over the past decade. In the United States, few population
      based studies have explored the contemporary epidemiology and outcomes of
      endocarditis. Objective: To quantify trends in the incidence and etiologies of
      infective endocarditis in the United States. Design, Setting, and Participants:
      Retrospective population epidemiology study of patients hospitalized with a first
      episode of endocarditis identified from mandatory state databases in California
      and New York State between January 1, 1998, and December 31, 2013. Exposure:
      Infective endocarditis. Main Outcomes and Measures: Outcomes were crude and
      standardized incidence of endocarditis and trends in patient characteristics and
      disease etiology. Trends in acquisition mode, organism, and mortality were
      analyzed. Results: Among 75 829 patients with first episodes of endocarditis
      (mean [SD] age, 62.3 [18.9] years; 59.1% male), the standardized annual incidence
      was stable between 7.6 (95% CI, 7.4 to 7.9) and 7.8 (95% CI, 7.6 to 8.0) cases
      per 100 000 persons (annual percentage change [APC], -0.06%; 95% CI, -0.3% to
      0.2%; P = .59). From 1998 through 2013, the proportion of patients with native
      valve endocarditis decreased (from 74.5% to 68.4%; APC, -0.7%; 95% CI, -0.9% to 
      0.5%; P < .001). Prosthetic-valve endocarditis increased (from 12.0% to 13.8%;
      APC, 1.3%; 95% CI, 0.8% to 1.7%; P < .001), and cardiac device-related
      endocarditis increased (from 1.3% to 4.1%; APC, 8.8%; 95% CI, 7.8% to 9.9%; P <
      .001). The proportion of patients with health care-associated nosocomial
      endocarditis decreased (from 17.7% to 15.3%; APC, -1.0%; 95% CI, -1.4% to -0.7%;
      P < .001). The proportion of patients with health care-associated nonnosocomial
      endocarditis increased (from 32.1% to 35.9%; APC, 0.8%; 95% CI, 0.5% to 1.1%; P <
      .001). The incidence of oral streptococcal endocarditis did not increase
      (unadjusted: APC, -0.1%; 95% CI, -0.8% to 0.6%; P = .77; adjusted: APC, -1.3%;
      95% CI, -1.8% to -0.7%; P < .001). Crude 90-day mortality was unchanged (from
      23.9% to 24.2%; APC, -0.3%; 95% CI, -1.0% to 0.4%; P = .44); adjusted risk of 90
      day mortality decreased (adjusted hazard ratio per year, 0.982; 95% CI, 0.978 to
      0.986; P < .001). Conclusions and Relevance: In California and New York State,
      the overall standardized incidence of infective endocarditis was stable from 1998
      through 2013, with changes in patient characteristics and etiology over this
      time.

PMID- 28444281
TI  - Screening for Preeclampsia During Pregnancy.

PMID- 28444283
TI  - Navigating Transitions and Charting New Paths.

PMID- 28444280
TI  - Association of Postoperative High-Sensitivity Troponin Levels With Myocardial
      Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery.
AB  - Importance: Little is known about the relationship between perioperative high
      sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial
      injury after noncardiac surgery (MINS). Objective: To determine the association
      between perioperative hsTnT measurements and 30-day mortality and potential
      diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated
      with 30-day mortality). Design, Setting, and Participants: Prospective cohort
      study of patients aged 45 years or older who underwent inpatient noncardiac
      surgery and had a postoperative hsTnT measurement. Starting in October 2008,
      participants were recruited at 23 centers in 13 countries; follow-up finished in
      December 2013. Exposures: Patients had hsTnT measurements 6 to 12 hours after
      surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. Main
      Outcomes and Measures: A modified Mazumdar approach (an iterative process) was
      used to determine if there were hsTnT thresholds associated with risk of death
      and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day
      mortality of 3% or higher. To determine potential diagnostic criteria for MINS,
      regression analyses ascertained if postoperative hsTnT elevations required an
      ischemic feature (eg, ischemic symptom or electrocardiography finding) to be
      associated with 30-day mortality. Results: Among 21 842 participants, the mean
      age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after
      surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable
      analysis demonstrated that compared with the reference group (peak hsTnT <5
      ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less
      than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0%
      (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6%
      (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI,
      10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92),
      respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an
      increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An
      elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change >=5 ng/L
      or hsTnT >=65 ng/L) without an ischemic feature was associated with 30-day
      mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%;
      95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not
      experience an ischemic symptom. Conclusions and Relevance: Among patients
      undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days
      after surgery was significantly associated with 30-day mortality. Elevated
      postoperative hsTnT without an ischemic feature was also associated with 30-day
      mortality.

PMID- 28444285
TI  - Preeclampsia Screening: Evidence Report and Systematic Review for the US
      Preventive Services Task Force.
AB  - Importance: Preeclampsia is a complex disease of pregnancy with sometimes serious
      effects on maternal and infant morbidity and mortality. It is defined by
      hypertension after 20 weeks' gestation and proteinuria or other evidence of
      multisystem involvement. Objective: To systematically review the benefits and
      harms of preeclampsia screening and risk assessment for the US Preventive
      Services Task Force. Data Sources: MEDLINE, PubMed, and Cochrane Central Register
      of Controlled Trials databases from 1990 through September 1, 2015. Surveillance
      for new evidence in targeted publications was conducted through October 5, 2016.
      Study Selection: English-language trials and observational studies, including
      externally validated prediction models, of screening effectiveness, benefits, and
      harms from routine preeclampsia screening during pregnancy. Data Extraction and
      Synthesis: Independent dual review of article abstracts and full texts against a
      priori inclusion criteria. Meta-analysis was not performed because of clinical
      and statistical heterogeneity of included studies. Main Outcomes and Measures:
      Maternal and infant health outcomes, including eclampsia, stroke, stillbirth,
      preterm birth, and low birth weight; screening and risk prediction test
      performance; harms of screening and risk assessment. Results: Twenty-one studies
      (13 982 participants) were included. No studies directly compared the
      effectiveness of preeclampsia screening in a screened population vs an unscreened
      population; 1 US trial (n = 2764) found no difference in benefits or harms with
      fewer prenatal visits but was underpowered for rare, serious outcomes. For harms,
      a before-after comparison cohort noninferiority study of urine protein screening
      for specific indications compared with routine screening (n = 1952) did not
      identify harms with fewer urine screening tests. Four studies (n = 7123) reported
      external validation performance of 16 risk prediction models, 5 of which had good
      or better discrimination (c statistic >0.80) for prediction of preeclampsia, and
      positive predictive values of 4% in the largest, most applicable validation
      cohorts. Calibration was not reported despite being a key model performance
      measure. There were no studies of urine screening test performance conducted in
      asymptomatic primary care populations; 14 studies of protein urine test
      performance among women being evaluated for suspected preeclampsia (n = 1888) had
      wide-ranging test accuracy (sensitivity, 22%-100%; specificity, 36%-100%) and
      high statistical and clinical heterogeneity in tests used, eligibility criteria,
      and proteinuria prevalence (8.7%-93.8%). Conclusions and Relevance: Evidence to
      estimate benefits and harms of preeclampsia screening and the test performance of
      different screening approaches over the course of pregnancy was limited.
      Externally validated risk prediction models had limited applicability and lacked
      calibration and clinical implementation data needed to support routine use.
      Further research is needed to better inform risk-based screening approaches and
      improve screening strategies, given the complex pathophysiology and clinical
      unpredictability of preeclampsia.

PMID- 28444287
TI  - Certain Prescribing Patterns Lead to Long-term Opioid Use.

PMID- 28444288
TI  - US Suicide Rates Display Growing Geographic Disparity.

PMID- 28444286
TI  - Screening for Preeclampsia: US Preventive Services Task Force Recommendation
      Statement.
AB  - Importance: Preeclampsia affects approximately 4% of pregnancies in the United
      States. It is the second leading cause of maternal mortality worldwide and may
      lead to serious maternal complications, including stroke, eclampsia, and organ
      failure. Adverse perinatal outcomes for the fetus and newborn include
      intrauterine growth restriction, low birth weight, and stillbirth. Many of the
      complications associated with preeclampsia lead to early induction of labor or
      cesarean delivery and subsequent preterm birth. Subpopulation Considerations:
      Preeclampsia is more prevalent among African American women than among white
      women. Differences in prevalence may be, in part, due to African American women
      being disproportionally affected by risk factors for preeclampsia. African
      American women also have case fatality rates related to preeclampsia 3 times
      higher than rates among white women. Inequalities in access to adequate prenatal
      care may contribute to poor outcomes associated with preeclampsia in African
      American women. Objective: To update the 1996 US Preventive Services Task Force
      (USPSTF) recommendation on screening for preeclampsia. Evidence Review: The
      USPSTF reviewed the evidence on the accuracy of screening and diagnostic tests
      for preeclampsia, the potential benefits and harms of screening for preeclampsia,
      the effectiveness of risk prediction tools, and the benefits and harms of
      treatment of screen-detected preeclampsia. Findings: Given the evidence that
      treatment can reduce maternal and perinatal morbidity and mortality, and the well
      established accuracy of blood pressure measurements, the USPSTF found adequate
      evidence that screening for preeclampsia results in a substantial benefit for the
      mother and infant. In addition, there is adequate evidence to bound the harms of
      screening for and treatment of preeclampsia as no greater than small. Therefore,
      the USPSTF concludes with moderate certainty that there is a substantial net
      benefit of screening for preeclampsia in pregnant women. Conclusions and
      Recommendation: The USPSTF recommends screening for preeclampsia in pregnant
      women with blood pressure measurements throughout pregnancy. (B recommendation).

PMID- 28444289
TI  - "One Simply Doesn't Arbitrate Authorship of Thoughts": Socialized Medicine,
      Medical McCarthyism, and the Publishing of Rural Health and Medical Care (1948).

PMID- 28444291
TI  - Pasteurella aerogenes as an Asymptomatic Bacteriuria Agent.
AB  - 'Asymptomatic bacteriuria' (ASB) is isolation of a specified quantitative count
      of bacteria in an appropriately collected urine specimen obtained from a person
      without symptoms or signs referable to urinary infection. Catheterized specimens
      are less likely to be contaminated compared with voided specimens; therefore,
      positive cultures of catheterized specimens are more likely to reflect true
      bladder bacteriuria even with low colony counts. The common pathogens for ASB are
      Escherichia coli, Klebsiella and Streptococcus spp. Pasteurella spp. was not
      previously reported as an ASB agent. ASB is important for pregnant women,
      children, individuals with obstructive uropathy, chronic renal failure and
      neutropenia, before the urologic procedures and after renal transplantation.
      Treatment of ASB is required for above situations. We report an 11-year-old-girl
      with neurogenic bladder who made clean intermittent catheterization and had
      Pasteurella aerogenes as an ASB agent.

PMID- 28444292
TI  - Excess Radiation to Newborns Hospitalized in the Intensive Care Unit.
AB  - Newborns in intensive care units are generally subjected to a great number of X
      rays procedures and to the risk of radiation-induced damage. This study evaluated
      a possible excess radiation by excess of radiographs, excess of dose per
      radiograph or under-collimation of the X-ray beam. The mean of X-rays per newborn
      was 12 (1-65) during a mean hospitalization of 29 d (1-226 d). The mean frequency
      was 0.8 X-ray exposures per newborn. About 13% of X-rays were performed without a
      well-defined clinical motivation. The mean entrance surface dose of 72 MUGy was
      higher than in most of comparative studies. Under-collimation caused non-thoracic
      structures to appear frequently on chest radiographs. This study indicates a
      possible reduction in X-rays exposures by applying the justification principle
      for each X-ray procedure, recommends a multiprofessional work in the attempt to
      dose optimization, and shows need of correctly use of collimation system to avoid
      irradiation of non-thoracic structures.

PMID- 28444290
TI  - Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1.
      Evidence from genetic, epidemiologic, and clinical studies. A consensus statement
      from the European Atherosclerosis Society Consensus Panel.
AB  - Aims: To appraise the clinical and genetic evidence that low-density lipoproteins
      (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results:
      We assessed whether the association between LDL and ASCVD fulfils the criteria
      for causality by evaluating the totality of evidence from genetic studies,
      prospective epidemiologic cohort studies, Mendelian randomization studies, and
      randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL
      burden is usually estimated by determination of plasma LDL cholesterol level (LDL
      C). Rare genetic mutations that cause reduced LDL receptor function lead to
      markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas
      rare variants leading to lower LDL-C are associated with a correspondingly lower
      risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies,
      Mendelian randomization studies, and randomized trials including more than 2
      million participants with over 20 million person-years of follow-up and over 150
      000 cardiovascular events demonstrate a remarkably consistent dose-dependent log
      linear association between the absolute magnitude of exposure of the vasculature
      to LDL-C and the risk of ASCVD; and this effect appears to increase with
      increasing duration of exposure to LDL-C. Both the naturally randomized genetic
      studies and the randomized intervention trials consistently demonstrate that any
      mechanism of lowering plasma LDL particle concentration should reduce the risk of
      ASCVD events proportional to the absolute reduction in LDL-C and the cumulative
      duration of exposure to lower LDL-C, provided that the achieved reduction in LDL
      C is concordant with the reduction in LDL particle number and that there are no
      competing deleterious off-target effects. Conclusion: Consistent evidence from
      numerous and multiple different types of clinical and genetic studies
      unequivocally establishes that LDL causes ASCVD.

PMID- 28444293
TI  - Regulation of hematopoiesis and immune responses by long non-coding RNAs.
AB  - Since the first draft of the human genome sequence was released in 2001,
      unprecedentedly rapid progress has been made in whole genome-wide approaches by
      utilizing next-generation-sequencing technologies. The last decade alone has
      generated enormous data in the forms of exome sequencing, transcriptomes,
      transcription factor occupancy, genomic variation profiling and epigenetic
      modifications. One of the most striking realizations from sequencing studies has
      been the discovery and characterization of non-coding RNAs (ncRNAs). Although the
      extent to which ncRNAs are functional in vivo is still a controversial topic,
      there is at least a consensus that some ncRNAs are functional and that they play
      various roles in biology. Among the several kinds of ncRNAs, long ncRNAs
      (lncRNAs) in particular have received more attention because they have a larger
      potential to act as multifunctional regulators. Not surprisingly, researchers in
      the field of immunology have started to examine ncRNAs as new regulatory
      mechanisms. In this review, we will summarize some lncRNAs that have been
      reported to function in the immune system and then argue that there is still a
      long way to go before we can achieve a complete understanding of lncRNAs.

PMID- 28444294
TI  - ST3268: a geographically widespread primate MRSA clone.

PMID- 28444296
TI  - Challenging the myths of cardiac amyloidosis.

PMID- 28444295
TI  - Features of Dengue and Chikungunya Infections of Colombian Children under 24
      Months of Age Admitted to the Emergency Department.
AB  - We aimed to assess clinical and laboratory differences between dengue and
      chikungunya in children <24 months of age in a comparative study. We collected
      retrospective clinical and laboratory data confirmed by NS1/IgM for dengue for 19
      months (1 January 2013 to 17 August 2014). Prospective data for chikungunya
      confirmed by real-time polymerase chain reaction were collected for 4 months (22
      September 2014-14 December 2014). Sensitivity and specificity [with 95%
      confidence interval (CI)] were reported for each disease diagnosis. A platelet
      count <150 000 cells/ml at emergency admission best characterized dengue, with a
      sensitivity of 67% (95% CI, 53-79) and specificity of 95% (95% CI, 82-99). The
      algorithm developed with classification and regression tree analysis showed a
      sensitivity of 93% (95% CI, 68-100) and specificity of 38% (95% CI, 9-76) to
      diagnose dengue. Our study provides potential differential characteristics
      between chikungunya and dengue in young children, especially low platelet counts.

PMID- 28444297
TI  - Rapid and Parallel Adaptive Evolution of the Visual System of Neotropical Midas
      Cichlid Fishes.
AB  - Midas cichlid fish are a Central American species flock containing 13 described
      species that has been dated to only a few thousand years old, a historical
      timescale infrequently associated with speciation. Their radiation involved the
      colonization of several clear water crater lakes from two turbid great lakes.
      Therefore, Midas cichlids have been subjected to widely varying photic conditions
      during their radiation. Being a primary signal relay for information from the
      environment to the organism, the visual system is under continuing selective
      pressure and a prime organ system for accumulating adaptive changes during
      speciation, particularly in the case of dramatic shifts in photic conditions.
      Here, we characterize the full visual system of Midas cichlids at organismal and
      genetic levels, to determine what types of adaptive changes evolved within the
      short time span of their radiation. We show that Midas cichlids have a diverse
      visual system with unexpectedly high intra- and interspecific variation in color
      vision sensitivity and lens transmittance. Midas cichlid populations in the clear
      crater lakes have convergently evolved visual sensitivities shifted toward
      shorter wavelengths compared with the ancestral populations from the turbid great
      lakes. This divergence in sensitivity is driven by changes in chromophore usage,
      differential opsin expression, opsin coexpression, and to a lesser degree by
      opsin coding sequence variation. The visual system of Midas cichlids has the
      evolutionary capacity to rapidly integrate multiple adaptations to changing light
      environments. Our data may indicate that, in early stages of divergence, changes
      in opsin regulation could precede changes in opsin coding sequence evolution.

PMID- 28444298
TI  - The Line-drawing Problem in Disease Definition.
AB  - Biological dysfunction is regarded, in many accounts, as necessary and perhaps
      sufficient for disease. But although disease is conceptualized as all-or-nothing,
      biological functions often differ by degree. A tension is created by attempting
      to use a continuous variable as the basis for a categorical definition, raising
      questions about how we are to pinpoint the boundary between health and disease.
      This is the line-drawing problem. In this paper, we show how the line-drawing
      problem arises within "dysfunction-requiring" accounts of disease, such as those
      of Christopher Boorse and Jerome Wakefield. We then provide several detailed
      examples to establish that biological dysfunction cannot provide a boundary. We
      examine potential ways of resolving the line-drawing problem, either by dropping
      one of the claims that generates it, or by appealing to additional criteria. We
      argue that two of these options are plausible, and that each of these can be
      applied with regard to different diseases.

PMID- 28444299
TI  - Environmental factors associated with disease flare in juvenile and adult
      dermatomyositis.
AB  - Objective: The aim was to assess environmental factors associated with disease
      flare in juvenile and adult dermatomyositis (DM). Methods: An online survey of DM
      patients from the USA and Canada examined smoking, sun exposure, infections,
      medications, vaccines, stressful life events and physical activity during the 6
      months before flares, or in the past 6 months in patients without flares.
      Differences were evaluated by chi 2 and Fisher's exact tests, and significant
      univariable results were examined in multivariable logistic regression.
      Residential locations before flare were correlated with the National Weather
      Service UV index. Results: Of 210 participants (164 juvenile and 46 adult DM),
      134 (63.8%) experienced a disease flare within 2 years of the survey. Subjects
      more often reported disease flare after sun exposure [odds ratio (OR) = 2.0, P =
      0.03], although use of photoprotective measures did not differ between those with
      and without flare. Urinary tract infections (OR = 16.4, P = 0.005) and
      gastroenteritis (OR = 3.2, P = 0.04) were more frequent in the preceding 6 months
      in those who flared. Subjects who flared recently used NSAIDS (OR = 3.0, P =
      0.0003), blood pressure medicines (OR = 3.5, P = 0.049) or medication for
      depression or mood changes (OR = 12.9, P = 0.015). Moving to a new house (OR =
      10.3, P = 0.053) was more common in those who flared. Only sun exposure (OR =
      2.2) and NSAIDs (OR = 1.9) were significant factors in multivariable analysis.
      Conclusion: Certain classes of environmental agents that have been associated
      with the initiation of DM, including sun exposure and medications, may also play
      a role in disease flares.

PMID- 28444300
TI  - Reproductive Justice: A Policy Window for Social Work Advocacy.
AB  - Reproductive rights are at risk in many parts of the United States. To inspire
      social workers to act, this article begins by defining and describing the
      concepts of reproductive rights and reproductive justice. Next, it summarizes
      threats to reproductive rights in five areas: preventing pregnancy, terminating
      pregnancy, pregnancy loss, personhood measures, and drug use during pregnancy.
      Applying John Kingdon's policy streams framework, the article urges more social
      workers to embrace the current policy window and advocate for pregnant women and
      others whose reproductive rights are in jeopardy. The article also provides
      suggestions for ways that social work practitioners, educators, and researchers
      can act to promote reproductive justice for all.

PMID- 28444301
TI  - Soybean NIMA-Related Kinase1 Promotes Plant Growth and Improves Salt and Cold
      Tolerance.
AB  - NEK (NIMA-related kinase) is known as a family of serine/threonine kinases which
      mainly participate in microtubule-related mitotic events in fungi, mammals and
      other eukaryotes. Our previous studies found that Arabidopsis NEK6 plays an
      important role in plant response to abiotic stress. We further investigated roles
      of the NEK family in soybean and found that at least eight members can respond to
      abiotic stresses. Among them, only GmNEK1, a novel NEK member which is distantly
      related to Arabidopsis NEK6, enhanced plant growth and promoted salt and cold
      tolerance in transgenic Arabidopsis plants. The growth of soybean plants
      harboring GmNEK1-overexpressing hairy roots under saline condition was also
      improved. A series of stress-related genes including RH3, CORI3 and ALDH10A8 were
      found to be up-regulated in GmNEK1-overexpressing Arabidopsis plants and soybean
      hairy roots. Moreover, soybean plants with GmRH3-overexpressing hairy roots
      exhibited increased salt tolerance, while soybean plants with GmRH3-RNAi (RNA
      interference) roots were more sensitive to salt stress than the wild-type plants.
      Our study uncovers a novel role for GmNEK1 in promoting plant adaptive growth
      under adverse conditions at least partially through up-regulation of GmRH3.
      Manipulation of these genes in soybean or other crops may improve growth and
      production under stress conditions.

PMID- 28444303
TI  - Testing Comparability Between Retrospective Life History Data and Prospective
      Birth Cohort Study Data.
AB  - Objectives: To determine whether comparable prospective and retrospective data
      present the same association between childhood and life course exposures and mid
      life wellbeing. Method: Prospective data is taken from the 1958 UK National Child
      Development Study at age 50 in 2008 and earlier sweeps (n = 8,033). Retrospective
      data is taken from the English Longitudinal Study of Ageing at ages 50-55 from a
      life history interview in 2007 (n = 921). Results: There is a high degree of
      similarity in the direction of association between childhood exposures that have
      been prospectively collected in National Child Development Study and
      retrospectively collected in English Longitudinal Study of Ageing and wellbeing
      outcomes in mid-life. However, the magnitude of these associations is attenuated
      substantially by the inclusion of measurements, which are difficult or impossible
      to capture retrospectively, and are only available in prospective data, such as
      childhood poverty, cognitive ability, and indices of social and emotional
      adjustment. Discussion: The findings on the one hand provide some reassurance to
      the growing literature using life history data to determine life course
      associations with later life wellbeing. On the other hand, the findings show an
      overestimation in the retrospective data, in part, arising from the absence in
      life history data of childhood measures that are not well suited to retrospective
      collection.

PMID- 28444302
TI  - Draft genome of the lined seahorse, Hippocampus erectus.
AB  - Background: The lined seahorse, Hippocampus erectus , is an Atlantic species and
      mainly inhabits shallow sea beds or coral reefs. It has become very popular in
      China for its wide use in traditional Chinese medicine. In order to improve the
      aquaculture yield of this valuable fish species, we are trying to develop genomic
      resources for assistant selection in genetic breeding. Here, we provide whole
      genome sequencing, assembly, and gene annotation of the lined seahorse, which can
      enrich genome resource and further application for its molecular breeding. A
      total of 174.6 Gb (Gigabase) raw DNA sequences were generated by the Illumina
      Hiseq2500 platform. The final assembly of the lined seahorse genome is around 458
      Mb, representing 94% of the estimated genome size (489 Mb by k-mer analysis). The
      contig N50 and scaffold N50 reached 14.57 kb and 1.97 Mb, respectively. Quality
      of the assembled genome was assessed by BUSCO with prediction of 85% of the known
      vertebrate genes and evaluated using the de novo assembled RNA-seq transcripts to
      prove a high mapping ratio (more than 99% transcripts could be mapped to the
      assembly). Using homology-based, de novo and transcriptome-based prediction
      methods, we predicted 20 788 protein-coding genes in the generated assembly,
      which is less than our previously reported gene number (23 458) of the tiger tail
      seahorse ( H. comes ). We report a draft genome of the lined seahorse. These
      generated genomic data are going to enrich genome resource of this economically
      important fish, and also provide insights into the genetic mechanisms of its
      iconic morphology and male pregnancy behavior.

PMID- 28444304
TI  - A frequent oligogenic involvement in congenital hypothyroidism.
AB  - Congenital hypothyroidism (CH), the most frequent form of preventable mental
      retardation, is predicted to have a relevant genetic origin. However, CH is
      frequently reported to be sporadic and candidate gene variations were found in
      <10% of the investigated patients. Here, we characterize the involvement of 11
      candidate genes through a systematic Next Generation Sequencing (NGS) analysis.
      The NGS was performed in 177 unrelated CH patients (94 gland-in-situ; 83
      dysgenesis) and in 3,538 control subjects. Non-synonymous or splicing rare
      variants (MAF < 0.01) were accepted, and their functional impact was predicted by
      a comprehensive bioinformatic approach and co-segregation studies. The frequency
      of variations in cases and controls was extended to 18 CH-unrelated genes. At
      least one rare variant was accepted in 103/177 patients. Monogenic recessive
      forms of the disease were found in five cases, but oligogenic involvement was
      detected in 39 patients. The 167 variations were found to affect all genes
      independently of the CH phenotype. These findings were replicated in an
      independent cohort of additional 145 CH cases. When compared to 3,538 controls,
      the CH population was significantly enriched with disrupting variants in the
      candidate genes (P = 5.5 * 10-7), but not with rare variations in CH-unrelated
      genes. Co-segregation studies of the hypothyroid phenotype with multiple gene
      variants in several pedigrees confirmed the potential oligogenic origin of CH.
      The systematic NGS approach reveals the frequent combination of rare variations
      in morphogenetic or functional candidate genes in CH patients independently of
      phenotype. The oligogenic origin represents a suitable explanation for the
      frequent sporadic CH occurrence.

PMID- 28444305
TI  - Dissemination of gastroenteric viruses in the production of lettuce in developing
      countries: a public health concern.
AB  - Investigation of major viruses responsible for acute viral gastroenteritis, such
      as norovirus (NoV), rotavirus species A (RVA) and human adenovirus (HAdV), was
      conducted in the mountainous region of the state of Rio de Janeiro in a lettuce
      producing area. Irrigation water and lettuce samples were collected at different
      production stages. Viruses were concentrated using an adsorption-elution method
      and detected by quantitative polymerase chain reaction (qPCR). We detected HAdV
      in all collection points, although no virus infectivity was shown. The RVA was
      the most prevalent virus from both water (16.7% [10/60]) and lettuce samples
      (11.1% [4/36]), with loads ranging from 2.97 * 102 to 6.88 * 103 genomic copies
      per litre (gc L-1) and 6.24 * 102 to 1.30 * 104 gc per 25 g, respectively. NoV
      was detected in 8.33% [8/96] in water and lettuce samples, with concentrations
      ranging from 7.29 * 101 to 1.92 * 103 gc L-1 and from 4.29 * 101 to 2.98 * 103 gc
      25 g-1, respectively. Escherichia coli values also demonstrated poor quality of
      the irrigation and washing water. The presence of at least two different virus
      strains in all sites reveals the need to improve basic sanitation measures in
      order to increase food safety.

PMID- 28444306
TI  - Immunoglobulin-Based Investigation of Spontaneous Resolution of Chlamydia
      trachomatis Infection.
AB  - Chlamydia trachomatis elementary body enzyme-linked immunosorbent assay (ELISA)
      was used to investigate serum anti-CT immunoglobulin G1 (IgG1; long-lived
      response) and immunoglobulin G3 (IgG3; short-lived response indicating more
      recent infection) from treatment (enrollment) and 6-month follow-up visits in 77
      women previously classified as having spontaneous resolution of chlamydia. Of
      these women, 71.4% were IgG1+IgG3+, consistent with more recent chlamydia
      resolution. 15.6% were IgG3- at both visits, suggesting absence of recent
      chlamydia. Using elementary body ELISA, we demonstrated approximately 1 in 6
      women classified as having spontaneous resolution of chlamydia might have been
      exposed to C. trachomatis but not infected. Further, we classified their possible
      infection stage.

PMID- 28444307
TI  - Left atrial volume predicts atrial fibrillation recurrence after radiofrequency
      ablation: a meta-analysis.
AB  - Aims: Left atrial (LA) diameter is a predictor of atrial fibrillation (AF)
      recurrence following radiofrequency catheter ablation (RFA). However, LA volume
      (LAV) is more accurate in assessing LA size. Studies evaluating LAV as a
      predictor of AF recurrence are contradictory; therefore, we performed a meta
      analysis to assess whether LAV is an independent predictor of AF recurrence
      following RFA. Methods and results: All studies reporting LAV/LAV index (LAVi) as
      a predictor of AF recurrence following RFA were included. For studies reporting
      mean LAV/ LAVi in patients with and without AF recurrence, standard difference in
      means (SDM) and standard errors were calculated, and combined using meta
      analytical techniques. For studies reporting adjusted odds ratio (OR) for AF
      recurrence based on LAV/LAVi, log ORs were combined using generic inverse
      variance. Twenty one studies (3822 subjects) were included. Meta-analysis of 11
      studies (1559 subjects) reporting LAV, showed that patients with AF recurrence
      had a higher mean LA volume compared to patients with no recurrence (SDM 0.801;
      CI 0.387-1.216). Data from 9 studies (1425 subjects) comparing LAVi showed that,
      patients with AF recurrence had a higher mean LAVi compared to patients with no
      recurrence (SDM-0.596; CI 0.305-0.888). Thirteen studies (2886 patients)
      reporting ORs for AF recurrence based on LAV/ LAVi, showed that LAV/LAVi was
      independently predictive of AF recurrence post-RFA (OR-1.032, CI- 1.012-1.052).
      Conclusions: Patients with AF recurrence following RFA have a higher mean
      LAV/LAVi compared to patients with no recurrence. Large LAV/LAVi increases the
      odds of AF recurrence post RFA.

PMID- 28444309
TI  - Frequency of Youth E-Cigarette, Tobacco, and Poly-Use in the United States, 2015:
      Update to Villanti et al., "Frequency of Youth E-Cigarette and Tobacco Use
      Patterns in the United States: Measurement Precision Is Critical to Inform Public
      Health".

PMID- 28444308
TI  - Investigating DNA supercoiling in eukaryotic genomes.
AB  - Supercoiling is a fundamental property of DNA, generated by polymerases and other
      DNA-binding proteins as a consequence of separating/bending the DNA double helix.
      DNA supercoiling plays a key role in gene expression and genome organization, but
      has proved difficult to study in eukaryotes because of the large, complex and
      chromatinized genomes. Key approaches to study DNA supercoiling in eukaryotes are
      (1) centrifugation-based or electrophoresis-based techniques in which supercoiled
      plasmids extracted from eukaryotic cells form a compacted writhed structure that
      migrates at a rate proportional to the level of DNA supercoiling; (2) in vivo
      approaches based on the preferential intercalation of psoralen molecules into
      under-wound DNA. Here, we outline the principles behind these techniques and
      discuss key discoveries, which have confirmed the presence and functional
      potential of unconstrained DNA supercoiling in eukaryotic genomes.

PMID- 28444310
TI  - Arl3 and RP2 regulate the trafficking of ciliary tip kinesins.
AB  - Ciliary trafficking defects are the underlying cause of many ciliopathies,
      including Retinitis Pigmentosa (RP). Anterograde intraflagellar transport (IFT)
      is mediated by kinesin motor proteins; however, the function of the homodimeric
      Kif17 motor in cilia is poorly understood, whereas Kif7 is known to play an
      important role in stabilizing cilia tips. Here we identified the ciliary tip
      kinesins Kif7 and Kif17 as novel interaction partners of the small GTPase Arl3
      and its regulatory GTPase activating protein (GAP) Retinitis Pigmentosa 2 (RP2).
      We show that Arl3 and RP2 mediate the localization of GFP-Kif17 to the cilia tip
      and competitive binding of RP2 and Arl3 with Kif17 complexes. RP2 and Arl3 also
      interact with another ciliary tip kinesin, Kif7, which is a conserved regulator
      of Hedgehog (Hh) signaling. siRNA-mediated loss of RP2 or Arl3 reduced the level
      of Kif7 at the cilia tip. This was further validated by reduced levels of Kif7 at
      cilia tips detected in fibroblasts and induced pluripotent stem cell (iPSC) 3D
      optic cups derived from a patient carrying an RP2 nonsense mutation c.519C > T
      (p.R120X), which lack detectable RP2 protein. Translational read-through inducing
      drugs (TRIDs), such as PTC124, were able to restore Kif7 levels at the ciliary
      tip of RP2 null cells. Collectively, our findings suggest that RP2 and Arl3
      regulate the trafficking of specific kinesins to cilia tips and provide
      additional evidence that TRIDs could be clinically beneficial for patients with
      this retinal degeneration.

PMID- 28444312
TI  - Early posthatch thermal stress affects breast muscle development and satellite
      cell growth and characteristics in broilers.
AB  - Heat or cold stress, can disrupt well-being and physiological responses in birds.
      This study aimed to elucidate the effects of continuous heat exposure in the
      first 2 wk of age on muscle development in broilers, with an emphasis on the
      pectoralis muscle satellite cell population. Chicks were reared for 13 d under
      either commercial conditions or a temperature regime that was 5 degrees C higher.
      Body and muscle weights, as well as absolute muscle growth were lower in heat
      exposed chicks from d 6 onward. The number of satellite cells derived from the
      experimental chicks was higher in the heat-treated group on d 3 but lower on d 8
      and 13 compared to controls. This was reflected in a lower number of myonuclei
      expressing proliferating nuclear cell antigen in cross sections of pectoralis
      major muscle sampled on d 8. However, a TUNEL assay revealed similar cell
      survival in both groups. Mean myofiber diameter and distribution were lower in
      muscle sections sampled on d 8 and 13 in heat-treated versus control group,
      suggesting that the lower muscle growth is due to changes in muscle hypertrophy.
      Oil-Red O staining showed a higher number of satellite cells with lipids in the
      heat-treated compared to the control group on these days. Moreover, lipid
      deposition was observed in pectoralis muscle cross sections derived from the heat
      treated chicks on d 13, whereas the controls barely exhibited any lipid staining.
      The gene and protein expression levels of CCAAT/enhancer binding protein beta in
      pectoralis muscle from the heat-treated group were significantly higher on d 13
      than in controls, while myogenin levels were similar. The results suggest high
      sensitivity of muscle progenitor cells in the early posthatch period at a time
      when they are highly active, to chronic heat exposure, leading to impaired
      myogenicity of the satellite cells and increased fat deposition.

PMID- 28444311
TI  - Expression of ALS/FTD-linked mutant CCNF in zebrafish leads to increased cell
      death in the spinal cord and an aberrant motor phenotype.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal
      neurodegenerative disease characterised by the death of upper and lower motor
      neurons. Approximately 10% of cases have a known family history of ALS and
      disease-linked mutations in multiple genes have been identified. ALS-linked
      mutations in CCNF were recently reported, however the pathogenic mechanisms
      associated with these mutations are yet to be established. To investigate
      possible disease mechanisms, we developed in vitro and in vivo models based on an
      ALS-linked missense mutation in CCNF. Proteomic analysis of the in vitro models
      identified the disruption of several cellular pathways in the mutant model,
      including caspase-3 mediated cell death. Transient overexpression of human CCNF
      in zebrafish embryos supported this finding, with fish expressing the mutant
      protein found to have increased levels of cleaved (activated) caspase-3 and
      increased cell death in the spinal cord. The mutant CCNF fish also developed a
      motor neuron axonopathy consisting of shortened primary motor axons and increased
      frequency of aberrant axonal branching. Importantly, we demonstrated a
      significant correlation between the severity of the CCNF-induced axonopathy and a
      reduced motor response to a light stimulus (photomotor response). This is the
      first report of an ALS-linked CCNF mutation in vivo and taken together with the
      in vitro model identifies the disruption of cell death pathways as a significant
      consequence of this mutation. Additionally, this study presents a valuable new
      tool for use in ongoing studies investigating the pathobiology of ALS-linked CCNF
      mutations.

PMID- 28444313
TI  - Genotypic variation in transpiration efficiency due to differences in
      photosynthetic capacity among sugarcane-related clones.
AB  - Sugarcane, derived from the hybridization of Saccharum officinarum*Saccharum
      spontaneum, is a vegetative crop in which the final yield is highly driven by
      culm biomass production. Cane yield under irrigated or rain-fed conditions could
      be improved by developing genotypes with leaves that have high intrinsic
      transpiration efficiency, TEi (CO2 assimilation/stomatal conductance), provided
      this is not offset by negative impacts from reduced conductance and growth rates.
      This study was conducted to partition genotypic variation in TEi among a sample
      of diverse clones from the Chinese collection of sugarcane-related germplasm into
      that due to variation in stomatal conductance versus that due to variation in
      photosynthetic capacity. A secondary goal was to define protocols for optimized
      larger-scale screening of germplasm collections. Genotypic variation in TEi was
      attributed to significant variation in both stomatal and photosynthetic
      components. A number of genotypes were found to possess high TEi as a result of
      high photosynthetic capacity. This trait combination is expected to be of
      significant breeding value. It was determined that a small number of observations
      (16) is sufficient for efficiently screening TEi in larger populations of
      sugarcane genotypes The research methodology and results reported are encouraging
      in supporting a larger-scale screening and introgression of high transpiration
      efficiency in sugarcane breeding. However, further research is required to
      quantify narrow sense heritability as well as the leaf-to-field translational
      potential of genotypic variation in transpiration efficiency-related traits
      observed in this study.

PMID- 28444314
TI  - Cold Disinfestation of "Hass" Avocado (Persia americana) of Three Species of
      Fruit Fly (Diptera: Tephritidae)-Ceratitis capitata, Ceratitis rosa, and
      Ceratitis cosyra.
AB  - The avocado industry is important in South Africa, but access to certain markets
      is impeded by the presence of phytosanitary pests. One of the ways of securing
      entry to these markets is to demonstrate that a mitigating treatment will result
      in there being a negligible chance of accidental importation. In cold treatment
      comparative studies at 0  degrees C and 2  degrees C of immature stages of
      Ceratitis capitata (Wiedemann), Ceratitis rosa Karsch, and Ceratitis cosyra
      (Walker) in "Hass" avocado, the third instar of C. cosyra was shown to be the
      most cold tolerant. This larval life stage was used in a large-scale trial to
      test treatment efficacy at 2  degrees C, a temperature known to be the better for
      fruit quality. There were no survivors from the 49,795 individual fruit fly
      larvae subjected to the cold treatment at 2  degrees C for 20 d. It is argued
      that, although this level of assessment falls short of the Probit 9 level
      normally required for fruit fly, they are rarely found in avocado fruit and that
      the level of disinfestation obtained is more than sufficient to achieve
      quarantine security.

PMID- 28444315
TI  - Towards the early detection of beta-lactamase-producing Enterobacteriaceae by
      MALDI-TOF MS analysis.
AB  - Objectives: Development of a novel MALDI-TOF MS-based method for the rapid
      detection of ESBL-producing Enterobacteriaceae. Methods: The method was evaluated
      in terms of sensitivity, specificity and turnaround time regarding the antibiotic
      used (cefotaxime, ceftazidime, ceftriaxone, cefpodoxime or cefepime) and the
      performance of the automated MBT STAR-BL software (Bruker Daltonik GmbH, Germany)
      relative to qualitative interpretation of spectra for detecting beta-lactamase
      resistance by MALDI-TOF MS (Bruker Daltonik) in a collection of 11 isogenic
      Escherichia coli control strains expressing different beta-lactamases. Finally,
      for clinical validation, beta-lactamase activity was determined under previously
      evaluated conditions in 100 clinical isolates previously characterized by PCR and
      sequencing. Results: Clinical validation of the assay showed 100% sensitivity and
      specificity for detecting beta-lactam resistance in 30 min by measuring
      hydrolysis of ceftriaxone (0.50 mg/mL) with the automated MBT STAR-BL software.
      Regarding the antibiotics evaluated, ceftriaxone yielded 70% more positive
      results than cefotaxime, 80% more than ceftazidime and 20% more than cefpodoxime,
      with 100% specificity. Cefepime revealed 100% sensitivity, but only 27%
      specificity. For the same incubation time, the automated software yielded on
      average 41% more positive results in relation to detecting resistance than
      qualitative interpretation of spectra. Conclusions: Our clinical validation of
      the method proved it to be highly reliable, simple to perform and time saving,
      transforming beta-lactam resistance detection by MALDI-TOF MS into a ready-to-use
      technique in clinical laboratories.

PMID- 28444317
TI  - Undocumented and documented migrants with chronic diseases in Family Practice in
      the Netherlands.
AB  - Background: Undocumented migrants (UM) face many barriers in accessing
      healthcare. It is unknown how these affect the care of UM with chronic diseases
      in general practices. In the Netherlands, a General practitioner (GP) is the
      gatekeeper to the healthcare system and primary care provider for UM. Objective:
      To get insight into GP care for chronic diseases in UM compared with documented
      migrants (DM). Methods: A survey study of medical records of UM and DM in five
      general practices in the Netherlands with extensive experience in caring for UM.
      UM and DM were matched for gender, age and region of origin. Consultation rates,
      values of HbA1C, blood pressure, spirometry, number of referrals and medicine
      prescriptions were compared in all people with cardiovascular disease, diabetes
      or asthma/ COPD. Results: In overall, 729 migrants were included (407 UM and 322
      DM). UM consulted their GP significantly less often than DM (3.24 versus 5.04
      times a year). UM with cardiovascular disease had a slightly higher blood
      pressure (148.1 versus 140.8 mmHg), and UM with diabetes had their blood pressure
      checked less frequently (0.70 versus 1.95 times a year). Overall however, the
      differences between UM and DM with chronic diseases were small. Conclusion:
      Undocumented migrants with chronic diseases in general practices in the
      Netherlands that are experienced in caring for UM receive to a large extent
      equitable care compared to documented migrants.

PMID- 28444316
TI  - Oxytocin facilitates reciprocity in social communication.
AB  - Synchrony in social groups may confer significant evolutionary advantages by
      improving group cohesion and social interaction. However, the neurobiological
      mechanisms translating social synchrony into refined social information
      transmission between interacting individuals are still elusive. In two
      successively conducted experiments involving a total of 306 healthy volunteers,
      we explored the involvement of the neuropeptide oxytocin (OXT) in reciprocal
      social interaction. First, we show that synchronous social interactions evoke
      heightened endogenous OXT release in dyadic partners. In a second step, we
      examined the consequences of elevated OXT concentrations on emotion transmission
      by intranasally administering synthetic OXT before recording emotional
      expressions. Intriguingly, our data demonstrate that the subjects' facial and
      vocal expressiveness of fear and happiness is enhanced after OXT compared with
      placebo administration. Collectively, our findings point to a central role of
      social synchrony in facilitating reciprocal communication between individuals via
      heightened OXT signaling. Elevated OXT concentrations among synchronized
      individuals seem to augment the partners' emotional expressiveness, thereby
      contributing to improved transmission of emotional information in social
      communication.

PMID- 28444318
TI  - Psychiatric Morbidity in Children with HIV/AIDS at a Tertiary Health Institution
      in North-central Nigeria.
AB  - Introduction: Children with human immunodeficiency virus (HIV) infection are
      living longer with the infection and are at risk of different complications. We
      assessed for the prevalence of and associated factors for psychiatric morbidity
      among HIV-infected children in a tertiary facility in Ilorin, Nigeria. Methods: A
      descriptive cross-sectional, two-staged study involving 196 HIV-positive children
      (6-17 years). A semi-structured questionnaire and psychological instruments were
      used for the study. Results: Thirty-eight (19.4%) children had psychiatric
      disorders: attention-deficit hyperactivity disorder and enuresis. Single
      parenthood, HIV clinical stages and complications were associated with
      psychiatric morbidity. Linear combination of the risk factors was not related to
      the psychiatric disorder. Bivariate correlation analysis showed the tendency to
      develop psychiatric disorder among the children was positively correlated with
      complications in the child and the person the child resides with. Conclusions:
      Complicated HIV infection and adverse life events result in elevated risk of
      having psychiatric morbidity.

PMID- 28444319
TI  - Gender differences in the correlation between prognosis and postoperative weight
      loss in patients with non-small cell lung cancer.
AB  - OBJECTIVES: The aim of this study was to investigate gender differences in the
      relationship between preoperative body mass index (BMI), postoperative body
      weight change and prognosis in patients with non-small cell lung cancer (NSCLC).
      METHODS: Two hundred and sixty-three patients with NSCLC were enrolled in this
      study. Preoperative BMI was categorized based on WHO definition as follows:
      underweight (BMI <18.5): 21 patients (8.0%), normal (18.5 ? BMI <25): 179
      patients (68%), overweight and obese (BMI ?25): 63 patients (24%). Several
      factors such as age, sex, cancer stage, body weight change and BMI were recorded
      and correlated to the postoperative overall survival (OS). RESULTS: For male
      patients, those in the low-BMI group had the worst prognosis (P < 0.05) whereas
      female patients with low BMI did not. Male patients with low BMI had
      statistically significant poorer prognosis compared to corresponding female
      patients (P < 0.05). Male patients with more than 5% body weight loss within 1
      year after operation when compared to preoperative body weight had poorer
      prognosis than those with less than 5% body weight loss (P < 0.001). Furthermore,
      these male patients had statistically significant worse prognosis than the
      corresponding female patients (P < 0.05). In multivariable analysis, gender, more
      than 5% of body weight loss compared to preoperative body weight, and
      pathological stage were independent prognostic factors in NSCLC. CONCLUSIONS:
      This study illustrates significant gender differences in the relationship between
      prognosis and BMI or body weight change in patients with postoperative NSCLC.

PMID- 28444320
TI  - Complex Skill Training Transfers to Improved Performance and Control of Simpler
      Tasks After Stroke.
AB  - Background: Given limited therapy time, it is important to practice tasks that
      optimize transfer to other tasks that cannot be practiced during therapy.
      However, little is known about how tasks can be selected for practice to optimize
      generalization. Objective: One dimension of task selection is the complexity of
      the task. The purpose of the current study was to test if learning of a complex
      motor skill with the paretic arm would transfer to a simpler unpracticed goal
      directed reaching task. Design: This is an observational study, repeated measures
      design. Methods: Fifteen participants with mild-to-moderate stroke practiced a
      complex motor skill using their paretic arm for 2 consecutive days. Complex skill
      learning was quantified using change in the speed-accuracy trade-off from
      baseline to 1 day and 1 month post-practice. Motor transfer was assessed as the
      change in goal-directed planar reaching performance and kinematics from 2
      baselines to 1 day and 1 month post-practice. Nine additional participants with
      stroke were recruited as the test-alone group who only participated in the
      transfer tests to rule out the effects of repeated testing. Results: Practice
      improved the speed-accuracy trade-off for the practiced complex skill that was
      retained over a period of 1 month. Importantly, complex skill practice, but not
      repeated testing alone, improved the long-term performance and kinematics of the
      unpracticed simpler goal-directed planar reaching task. Improvements in the
      unpracticed transfer task (reaching) strongly correlated with improvements in the
      practiced complex motor skill. Limitations: We did not have a comparison stroke
      group that practiced task-specific reaching movements. Conclusions: Given the
      limited number of tasks that can be practiced during therapy, training complex
      tasks may have an added advantage of transfer to improved simpler task
      performance.

PMID- 28444321
TI  - Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention
      Deficit/Hyperactivity Disorder.
AB  - Introduction: Individuals with attention deficit/hyperactivity disorder (ADHD)
      are susceptible to earlier and more severe nicotine addiction. To shed light on
      the relationship between nicotine and ADHD, we examined nicotine's effects on
      functional brain networks in an animal model of ADHD. Methods: Awake magnetic
      resonance imaging was used to compare functional connectivity in adolescent (post
      natal day 44 +/- 2) males of the spontaneously hypertensive rat (SHR) strain and
      two control strains, Wistar-Kyoto and Sprague-Dawley (n = 16 each). We analyzed
      functional connectivity immediately before and after nicotine exposure (0.4 mg/kg
      base) in naive animals, using a region-of-interest approach focussing on 16
      regions previously implicated in reward and addiction. Results: Relative to the
      control groups, the SHR strain demonstrated increased functional connectivity
      between the ventral tegmental area (VTA) and retrosplenial cortex in response to
      nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA
      substantia nigra connectivity in response to a saline injection in the SHR was
      absent following a nicotine injection, suggesting that nicotine normalized
      function in this circuit. Conclusions: In the SHR, nicotine triggered an atypical
      response in one VTA circuit while normalizing activity in another. The VTA has
      been widely implicated in drug reward. Our data suggest that increased
      susceptibility to nicotine addiction in individuals with ADHD may involve altered
      responses to nicotine involving VTA circuits. Implications: Nicotine addiction is
      more common among individuals with ADHD. We found that two circuits involving the
      VTA responded differently to nicotine in animals that model ADHD in comparison to
      two control strains. In one circuit, nicotine normalized activity that was
      abnormal in the ADHD animals, while in the other circuit nicotine caused an
      atypical brain response in the ADHD animals. The VTA has been implicated in drug
      reward. Our results would be consistent with an interpretation that nicotine may
      normalize abnormal brain activity in ADHD, and that nicotine may be more
      rewarding for individuals with ADHD.

PMID- 28444323
TI  - Effectiveness of Rotavirus Vaccination: A Systematic Review of the First Decade
      of Global Postlicensure Data, 2006-2016.
AB  - Two rotavirus vaccines, Rotarix (RV1) and RotaTeq (RV5), were licensed for global
      use in 2006. A systematic review of 48 peer- reviewed articles with postlicensure
      data from 24 countries showed a median RV1 vaccine effectiveness (VE) of 84%,
      75%, and 57% in countries with low, medium, and high child mortality,
      respectively, and RV5 VE of 90% and 45% in countries with low and high child
      mortality, respectively. A partial vaccine series provided considerable
      protection, but not to the same level as a full series. VE tended to decline in
      the second year of life, particularly in medium- and high-mortality settings, and
      tended to be greater against more severe rotavirus disease. Postlicensure data
      from countries across geographic regions and with different child mortality
      levels demonstrate that under routine use, both RV1 and RV5 are effective against
      rotavirus disease, supporting the World Health Organization recommendation that
      all countries introduce rotavirus vaccine into their national immunization
      program.

PMID- 28444322
TI  - Fumigant Activity of Sweet Orange Essential Oil Fractions Against Red Imported
      Fire Ants (Hymenoptera: Formicidae).
AB  - Sweet orange oil fractions were prepared by molecular distillation of cold
      pressed orange oil from sample A (Citrus sinensis (L.) 'Hamlin' from America) and
      sample B (Citrus sinensis Osbeck 'Newhall' from China) respectively, and their
      fumigant activities against medium workers of red imported fire ants (Solenopsis
      invicta Buren) were investigated. The volatile composition of the orange oil
      fractions was identified and quantified using GC-MS. Fractions from sample A (A1,
      A2, and A3) contained 23, 37, and 48 chemical constituents, and fractions from
      sample B (B1, B2, and B3) contained 18, 29, and 26 chemical constituents,
      respectively. Monoterpenes were the most abundant components, accounting for
      73.56% to 94.86% of total orange oil fractions, among which D-limonene (65.28
      80.18%), beta-pinene (1.71-5.58%), 3-carene (0.41-4.01%), beta-phellandrene (0.58
      2.10%), and linalool (0.31-2.20%) were major constituents. Fumigant bioassay
      indicated that all orange oil fractions exerted good fumigant toxicity against
      workers of fire ants at 3, 5, 10, and 20 mg/centrifuge tubes, and B1 had the
      strongest insecticidal potential, followed by A1, B2, A2, B3, and A3. The
      fractions composed of more high volatile molecules (A1 and B1) showed greater
      fumigant effects than others. Compounds linalool and D-limonene, which were the
      constituents of the orange oil, exhibited excellent fumigant toxicity against red
      imported fire ant workers. Linalool killed red imported fire ant workers
      completely at 5, 10, and 20 mg/tube after 8 h of treatment, and D-limonene
      induced >86% mortality at 8 h of exposure.

PMID- 28444324
TI  - Fitness Trade-Off Associated With Spinosad Resistance in Frankliniella
      occidentalis (Thysanoptera: Thripidae).
AB  - Frankliniella occidentalis (Pergande) is an economically important pest of
      agricultural crops. High resistance has been detected in field populations of F.
      occidentalis against the insecticide spinosad. In this study, we compared life
      history traits, body sizes, and feeding behaviors (recorded via an electrical
      penetration graph) of spinosad-susceptible (Ivf03) and spinosad-resistant (NIL-R)
      near-isogenic lines of F. occidentalis. Life table analysis showed that NIL-R had
      reduced female longevity and reduced fecundity. The relative fitness of NIL-R
      (0.43) was less than half that of Ivf03. NIL-R individuals were smaller than
      Ivf03 individuals, both in body length and body width at every stage. The number
      and duration of feeding activities were significantly reduced in NIL-R, with the
      exception of total duration of long-ingestion probes. These results suggest that
      there is a fitness trade-off associated with spinosad resistance in F.
      occidentalis, and that the development of resistance in this pest species may be
      reduced by rotating spinosad with other pesticides lacking cross-resistance.

PMID- 28444325
TI  - Corrigendum.

PMID- 28444327
TI  - Reviving a Positive Discourse on Sexuality within Social Work.
AB  - Sexuality is not an invisible dimension within social work. Social workers are
      constantly engaged with aspects of sexuality across virtually all practice
      domains. Indeed, some of the most fundamental and frequent concerns of social
      workers involve sexual abuse, sexual violence, and HIV and other sexually
      transmitted infections. However, conversations about healthy sexuality, positive
      sexuality, or sexual well-being that are well ensconced in many disciplines are
      all but absent from current social work literature, education, and practice. In
      this academic silence, social work is missing a significant opportunity to
      contribute to the larger conversation around healthy sexuality in a way that
      illuminates a more holistic perspective and that acknowledges desire and sexual
      satisfaction across the spectrum, including among marginalized and oppressed
      groups. In this article, authors make the case for shifting away from a pervasive
      focus on sexuality as solely risk based to one of balance, incorporating the
      normative nature and importance of sexuality, intimacy, pleasure, and desire
      within social work curricula, practice, and dialogue in general. They encourage
      social workers to recognize sexuality as a critical site of intersectionality and
      argue for the integration of a multidimensional approach to sexuality within
      social work education, practice, and research.

PMID- 28444326
TI  - Preclinical Evidence That 5-HT1B Receptor Agonists Show Promise as Medications
      for Psychostimulant Use Disorders.
AB  - Background: 5-HT1B receptor agonists enhance cocaine intake during daily self
      administration sessions but decrease cocaine intake when tested after prolonged
      abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence
      dependent effects on methamphetamine intake. Methods: Male rats were trained to
      self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and
      variable ratio 5) and high (progressive ratio) effort schedules of reinforcement
      until intake was stable. Rats were then tested for the effects of the selective 5
      HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but
      clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on
      methamphetamine self-administration both before and after a 21-day forced
      abstinence period during which the rats remained in their home cages. Results:
      The inverted U-shaped, methamphetamine dose-response function for intake on the
      fixed ratio 5 schedule was shifted downward by CP 94,253 both before and after
      abstinence. The CP 94,253-induced decrease in methamphetamine intake was
      replicated in rats tested on a variable ratio 5 schedule, and the 5-HT1B receptor
      antagonist SB 224,289 (10 mg/kg) reversed this effect. CP 94,253 also attenuated
      methamphetamine intake on a progressive ratio schedule both pre- and
      postabstinence. Similarly, zolmitriptan attenuated methamphetamine intake on a
      variable ratio 5 schedule both pre- and postabstinence, and the latter effect was
      sustained after each of 2 more treatments given every 2 to 3 days prior to daily
      sessions. Conclusions: Unlike the abstinence-dependent effect of 5-HT1B receptor
      agonists on cocaine intake reported previously, both CP 94,253 and zolmitriptan
      decreased methamphetamine intake regardless of abstinence. These findings suggest
      that 5-HT1B receptor agonists may have clinical efficacy for psychostimulant use
      disorders.

PMID- 28444328
TI  - Multiple Aggregation Pathways in Human gammaS-Crystallin and Its Aggregation
      Prone G18V Variant.
AB  - Purpose: Cataract results from the formation of light-scattering precipitates due
      to point mutations or accumulated damage in the structural crystallins of the eye
      lens. Although excised cataracts are predominantly amorphous, in vitro studies
      show that crystallins are capable of adopting a variety of morphologies depending
      on the preparation method. Here we characterize thermal, pH-dependent, and UV
      irradiated aggregates from wild-type human gammaS-crystallin (gammaS-WT) and its
      aggregation-prone variant, gammaS-G18V. Methods: Aggregates of gammaS-WT and
      gammaS-G18V were prepared under acidic, neutral, and basic pH conditions and held
      at 25 degrees C or 37 degrees C for 48 hours. UV-induced aggregates were produced
      by irradiation with a 355-nm laser. Aggregation and fibril formation were
      monitored via turbidity and thioflavin T (ThT) assays. Aggregates were
      characterized using intrinsic aromatic fluorescence, powder x-ray diffraction,
      and mass spectrometry. Results: gammaS-crystallin aggregates displayed different
      characteristics depending on the preparation method. gammaS-G18V produced a
      larger amount of detectable aggregates than did gammaS-WT and at less-extreme
      conditions. Aggregates formed under basic and acidic conditions yielded elevated
      ThT fluorescence; however, aggregates formed at low pH did not produce strongly
      turbid solutions. UV-induced aggregates produced highly turbid solutions but
      displayed only moderate ThT fluorescence. X-ray diffraction confirms amyloid
      character in low-pH samples and UV-irradiated samples, although the relative
      amounts vary. Conclusions: gammaS-G18V demonstrates increased aggregation
      propensity compared to gammaS-WT when treated with heat, acid, or UV light. The
      resulting aggregates differ in their ThT fluorescence and turbidity, suggesting
      that at least two different aggregation pathways are accessible to both proteins
      under the conditions tested.

PMID- 28444329
TI  - The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial
      Dysfunction and Preferentially Affects LHON Mutant Cells.
AB  - Purpose: Benzalkonium chloride (BAK) is the most commonly used eye drop
      preservative. Benzalkonium chloride has been associated with toxic effects such
      as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical
      mechanism of ocular toxicity by BAK is unclear. In this study, we propose a
      mechanistic basis for BAK's adverse effects. Method: Mitochondrial O2 consumption
      rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells
      carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant
      mtDNA [11778(G>A)], were measured before and after acute treatment with BAK.
      Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also
      measured in the BAK-treated control: LHON mutant and human-derived trabecular
      meshwork cells (HTM3). Results: Benzalkonium chloride inhibited mitochondrial ATP
      (IC50, 5.3 MUM) and O2 consumption (IC50, 10.9 MUM) in a concentration-dependent
      manner, by directly targeting mitochondrial complex I. At its pharmaceutical
      concentrations (107-667 MUM), BAK inhibited mitochondrial function >90%. In
      addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells
      (IC50, 22.8 MUM) and induced apoptosis in HTM3 cells at similar concentrations.
      Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in
      HCEP cells (IC50, 3.8 MUM) at 50-fold lower concentrations than used in eye
      drops, and that cells bearing mitochondrial blindness (LHON) mutations are
      further sensitized to BAK's mitotoxic effect. Conclusions: Benzalkonium chloride
      inhibits mitochondria of human corneal epithelial cells and cells bearing LHON
      mutations at pharmacologically relevant concentrations, and we suggest this is
      the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should
      be avoided in patients with mitochondrial deficiency, including LHON patients,
      LHON carriers, and possibly primary open-angle glaucoma patients.

PMID- 28444330
TI  - Progress and challenges of engineering a biophysical CO2-concentrating mechanism
      into higher plants.
AB  - Growth and productivity in important crop plants is limited by the inefficiencies
      of the C3 photosynthetic pathway. Introducing CO2-concentrating mechanisms (CCMs)
      into C3 plants could overcome these limitations and lead to increased yields.
      Many unicellular microautotrophs, such as cyanobacteria and green algae, possess
      highly efficient biophysical CCMs that increase CO2 concentrations around the
      primary carboxylase enzyme, Rubisco, to enhance CO2 assimilation rates. Algal and
      cyanobacterial CCMs utilize distinct molecular components, but share several
      functional commonalities. Here we outline the recent progress and current
      challenges of engineering biophysical CCMs into C3 plants. We review the
      predicted requirements for a functional biophysical CCM based on current
      knowledge of cyanobacterial and algal CCMs, the molecular engineering tools and
      research pipelines required to translate our theoretical knowledge into practice,
      and the current challenges to achieving these goals.

PMID- 28444331
TI  - Improved implementation of the risk-adjusted Bernoulli CUSUM chart to monitor
      surgical outcome quality.
AB  - Methodology issue: The traditional implementation of the risk-adjusted Bernoulli
      cumulative sum (CUSUM) chart for monitoring surgical outcome quality requires
      waiting a pre-specified period of time after surgery before incorporating patient
      outcome information. Proposed solution: We propose a simple but powerful
      implementation of the risk-adjusted Bernoulli CUSUM chart that incorporates
      outcome information as soon as it is available, rather than waiting a pre
      specified period of time after surgery. Evaluation: A simulation study is
      presented that compares the performance of the traditional implementation of the
      risk-adjusted Bernoulli CUSUM chart to our improved implementation. We show that
      incorporating patient outcome information as soon as it is available leads to
      quicker detection of process deterioration. Advice to practitioners:
      Deterioration of surgical performance could be detected much sooner using our
      proposed implementation, which could lead to the earlier identification of
      problems.

PMID- 28444332
TI  - Mitochondrial Recombination and Introgression during Speciation by Hybridization.
AB  - Genome recombination is a major source of genotypic diversity and contributes to
      adaptation and speciation following interspecies hybridization. The contribution
      of recombination in these processes has been thought to be largely limited to the
      nuclear genome because organelles are mostly uniparentally inherited in animals
      and plants, which prevents recombination. Unicellular eukaryotes such as budding
      yeasts do, however, transmit mitochondria biparentally, suggesting that during
      hybridization, both parents could provide alleles that contribute to
      mitochondrial functions such as respiration and metabolism in hybrid populations
      or hybrid species. We examined the dynamics of mitochondrial genome transmission
      and evolution during speciation by hybridization in the natural budding yeast
      Saccharomyces paradoxus. Using population-scale mitochondrial genome sequencing
      in two endemic North American incipient species SpB and SpC and their hybrid
      species SpC*, we found that both parental species contributed to the hybrid
      mitochondrial genome through recombination. We support our findings by showing
      that mitochondrial recombination between parental types is frequent in
      experimental crosses that recreate the early step of this speciation event. In
      these artificial hybrids, we observed that mitochondrial genome recombination
      enhances phenotypic variation among diploid hybrids, suggesting that it could
      play a role in the phenotypic differentiation of hybrid species. Like the nuclear
      genome, the mitochondrial genome can, therefore, also play a role in hybrid
      speciation.

PMID- 28444333
TI  - A Non-Classical Member of the Protein Disulfide Isomerase Family, PDI7 of
      Arabidopsis thaliana, Localizes to the cis-Golgi and Endoplasmic Reticulum
      Membranes.
AB  - Members of the protein disulfide isomerase (PDI)-C subfamily are chimeric
      proteins containing the thioredoxin (Trx) domain of PDIs, and the conserved N-
      and C-terminal Pfam domains of Erv41p/Erv46p-type cargo receptors. They are
      unique to plants and chromalveolates. The Arabidopsis genome encodes three PDI-C
      isoforms: PDI7, PDI12 and PDI13. Here we demonstrate that PDI7 is a 65 kDa
      integral membrane glycoprotein expressed throughout many Arabidopsis tissues.
      Using a PDI7-specific antibody, we show through immunoelectron microscopy that
      PDI7 localizes to the endoplasmic reticulum (ER) and Golgi membranes in wild-type
      root tip cells, and was also detected in vesicles. Tomographic modeling of the
      Golgi revealed that PDI7 was confined to the cis-Golgi, and accumulated primarily
      at the cis-most cisterna. Shoot apical meristem cells from transgenic plants
      overexpressing PDI7 exhibited a dramatic increase in anti-PDI7 labeling at the
      cis-Golgi. When N- or C-terminal fusions between PDI7 and the green fluorescent
      protein variant, GFP(S65T), were expressed in mesophyll protoplasts, the fusions
      co-localized with the ER marker, ER-mCherry. However, when GFP(S65T) was
      positioned internally within PDI7 (PDI7-GFPint), the fusion strongly co-localized
      with the cis-Golgi marker, mCherry-SYP31, and faintly labeled the ER. In contrast
      to the Golgi-resident fusion protein (Man49-mCherry), PDI7-GFPint did not
      redistribute to the ER after brefeldin A treatment. Protease protection
      experiments indicated that the Trx domain of PDI7 is located within the ER/Golgi
      lumen. We propose a model where PDI-C isoforms function as cargo receptors for
      proteins containing exposed cysteine residues, cycling them from the Golgi back
      to the ER.

PMID- 28444334
TI  - Antiquity's Missive to Transhumanism1.
AB  - To reassure those concerned about wholesale discontinuity between human existence
      and posthumanity, transhumanists assert shared ground with antiquity on vital
      challenges and aspirations. Because their claims reflect key misconceptions,
      there is no shared vision for transhumanists to invoke. Having exposed their
      misuses of Prometheus, Plato, and Aristotle, I show that not only do
      transhumanists and antiquity crucially diverge on our relation to ideals,
      contrast-dependent aspiration, and worthy endeavors but that illumining this
      divide exposes central weaknesses in transhumanist argumentation. What is more,
      antiquity's handling of these topics suggests a way through the impasse in
      current enhancement debates about human "nature" and helps to resolve a tension
      within transhumanists' accounts of what our best moments signify about the
      ontological requirements for real flourishing.

PMID- 28444335
TI  - Incidence of IgA vasculitis in children estimated by four-source capture
      recapture analysis: a population-based study.
AB  - Objectives: The aim was to describe the epidemiological characteristics of
      childhood IgA vasculitis (IgAV) defined by the EULAR/PRINTO/Paediatric
      Rheumatology European Society criteria in a population-based sample from France
      and ascertain its incidence over 3 years by a four-source capture-recapture
      analysis. Methods: Cases were prospectively collected in Val de Marne county, a
      suburb of Paris, with 263 874 residents <15 years old. Children with incident
      IgAV living in this area from 2012 to 2014 were identified by four sources of
      case notification (emergency departments, paediatrics departments, private
      practice paediatricians and general practitioners). Annual incidence was
      calculated, and a capture-recapture analysis was used with log-linear modelling
      to estimate case-finding completeness. Results: We identified 147 incident cases
      [78 boys; mean age 6.5 (s.d.:2.6) years]. The annual incidence (95% CI) was 18.6
      (13.6, 24.5)/100 000 children. Although only 10% of children were exclusively
      identified by non-hospital sources, the completeness of case finding was 62%,
      with an undercount-corrected annual incidence (95% CI) of 29.9 (23.7, 37.3)/100
      000 children. The annual distribution of diagnoses consistently showed a trough
      in summer months; 72% of children had infectious symptoms (mainly upper
      respiratory tract) a few days before IgAV onset; and 23% had a North African
      background. Conclusion: Our study supports secular and geospatial stability in
      childhood IgAV incidence and adds further indirect evidence for a possible role
      of a ubiquitous, non-emerging infectious trigger. Incidence studies from
      understudied areas are needed to disentangle the role of genetic factors better.
      Capture-recapture analysis suggests that a substantial portion of IgAV cases may
      remain unrecognized in epidemiological surveys.

PMID- 28444337
TI  - Utility of a repeat renal biopsy in lupus nephritis: a single centre experience.
AB  - Background: The role of repeat renal biopsy in lupus nephritis (LN) to guide
      treatment or predict prognosis has been controversial. We assessed glomerular and
      tubulointerstitial histological characteristics of serial renal biopsies,
      correlations with clinical variables and the impact on subsequent management.
      Methods: Out of a large single-centre cohort of 270 biopsy-proven LN patients, 66
      (24%) had serial biopsies. LN classes based on glomerular pathology were defined
      according to the International Society of Nephrology/Renal Pathology Society 2003
      classification, while tubulointerstitial pathologies were evaluated using the
      revised Austin's semi-quantitative scoring system. Results: LN class transitions
      from proliferative (III and IV) to non-proliferative classes (II and V) were
      uncommon (n = 4, 7.7%), while non-proliferatives frequently switched to
      proliferative classes (n = 12, 63.2%) and were more likely to receive increased
      immunosuppression (P = 0.040). Biochemical or serological variables could not
      predict these histopathological transitions. Tubulointerstitial score (mean +/-
      standard deviation) progressed from 2.69 +/- 2.03 on reference to 3.78 +/- 2.03
      on repeat biopsy (P = 0.001). Serum creatinine levels correlated with the degree
      of tubular atrophy on both reference (r = 0.33, P = 0.048) and repeat biopsy (r =
      0.56, P < 0.001), and with interstitial scarring (r = 0.60, P < 0.001) on repeat
      biopsy. Greater interstitial inflammation on reference biopsy was associated with
      advanced interstitial scarring on repeat biopsies (r = 0.385, P = 0.009).
      Conclusions: Repeat renal biopsy is an important tool to guide management, in
      particular in those with initial class II or V who flare. Although class
      transitions cannot be predicted by clinical parameters, serum creatinine level
      correlates with the degree of tubulointerstitial damage.

PMID- 28444338
TI  - Aquatic Exercise for the Treatment of Hip and Knee Osteoarthritis.
AB  - <LEAP> highlights the findings and application of Cochrane reviews and other
      evidence pertinent to the practice of physical therapy. The Cochrane library is a
      respected source of reliable evidence related to health care. Cochrane systematic
      reviews explore the evidence for and against the effectiveness and
      appropriateness of interventions-medications, surgery, education, nutrition,
      exercise-and the evidence for and against the use of diagnostic tests for
      specific conditions. Cochrane reviews are designed to facilitate the decisions of
      clinicians, patients, and others in health care by providing a careful review and
      interpretation of research studies published in the scientific literature. Each
      article in this PTJ series summarizes a Cochrane review or other scientific
      evidence on a single topic and presents clinical scenarios based on real patients
      or programs to illustrate how the results of the review can be used to directly
      inform clinical decisions. This article focuses on an older adult with severe
      knee joint pain. Can aquatic exercise help this patient with knee osteoarthritis?

PMID- 28444336
TI  - Intradialytic hypotension, blood pressure changes and mortality risk in incident
      hemodialysis patients.
AB  - Background: Intradialytic hypotension (IDH) occurs frequently in maintenance
      hemodialysis (HD) patients and may be associated with higher mortality. We
      hypothesize that nadir intradialytic systolic blood pressure (niSBP) is inversely
      related to death risk while iSBP change (Delta) and IDH frequency are
      incrementally associated with all-cause mortality. Methods: In a US-based cohort
      of 112 013 incident HD patients over a 5-year period (2007-11), using niSBP,
      DeltaiSBP (pre-HD SBP minus niSBP) and IDH frequency (proportion of HD treatments
      with niSBP <90 mmHg) within the first 91 days of HD, we examined mortality
      predictability at 1, 2 and 5 years using Cox models and restricted cubic splines
      adjusted for case-mix, comorbidities and laboratory covariates. Results: We
      observed that niSBP of <90 and >=140 mmHg had a 5-year mortality hazard ratio
      (HR) (95% confidence interval) of 1.57 (1.47-1.67) and 1.25 (1.18-1.33),
      respectively, compared with niSBP 110 to <120 mmHg. DeltaiSBP of <15 and >=50
      compared with 21-30 mmHg had mortality HR of 1.31 (1.26-1.37) and 1.32 (1.24
      1.39), respectively. Among patients with >40% IDH frequency, we observed a
      mortality HR of 1.49 (1.42-1.57) compared with 0% IDH frequency in fully adjusted
      models. These associations were robust at 1 and 2 years of follow-up. Conclusion:
      In conclusion, we observed a U-shaped association between niSBP and DeltaiSBP and
      mortality and a direct linear relationship between IDH frequency and mortality.
      Our findings lend some prognostic insight of HD blood pressure and hemodynamics,
      and have the potential to guide blood pressure management strategies among the HD
      population.

PMID- 28444339
TI  - Comparison of plethysmographic and helium dilution lung volumes in patients with
      a giant emphysematous bulla as selection criteria for endobronchial valve
      implant.
AB  - OBJECTIVES: To assess whether the difference in lung volume measured with
      plethysmography and with the helium dilution technique could differentiate an
      open from a closed bulla in patients with a giant emphysematous bulla and could
      be used as a selection criterion for the positioning of an endobronchial valve.
      METHODS: We reviewed the data of 27 consecutive patients with a giant
      emphysematous bulla undergoing treatment with an endobronchial valve. In addition
      to standard functional and radiological examinations, total lung capacity and
      residual volume were measured with the plethysmographic and helium dilution
      technique. We divided the patients into 2 groups, the collapse or the no-collapse
      group, depending on whether the bulla collapsed or not after the valves were put
      in position. We statistically evaluated the intergroup differences in lung volume
      and outcome. RESULTS: In the no-collapse group (n = 6), the baseline
      plethysmographic values were significantly higher than the helium dilution
      volumes, including total lung capacity (188 +/- 14 vs 145 +/- 13, P = 0.0007) and
      residual volume (156 +/- 156 vs 115 +/- 15, P = 0.001). In the collapse group,
      there was no significant difference in lung volumes measured with the 2 methods.
      A difference in total lung capacity of <= 13% and in residual volume of <= 25%
      measured with the 2 methods predicted the collapse of the bulla with a success
      rate of 83% and 84%, respectively. Only the collapse group showed significant
      improvement in functional data. CONCLUSIONS: Similar values in lung volumes
      measured with the 2 methods support the hypothesis that the bulla communicates
      with the airway (open bulla) and thus is likely to collapse when the
      endobronchial valve is implanted. Further studies are needed to validate our
      model.

PMID- 28444340
TI  - LigParGen web server: an automatic OPLS-AA parameter generator for organic
      ligands.
AB  - The accurate calculation of protein/nucleic acid-ligand interactions or condensed
      phase properties by force field-based methods require a precise description of
      the energetics of intermolecular interactions. Despite the progress made in force
      fields, small molecule parameterization remains an open problem due to the
      magnitude of the chemical space; the most critical issue is the estimation of a
      balanced set of atomic charges with the ability to reproduce experimental
      properties. The LigParGen web server provides an intuitive interface for
      generating OPLS-AA/1.14*CM1A(-LBCC) force field parameters for organic ligands,
      in the formats of commonly used molecular dynamics and Monte Carlo simulation
      packages. This server has high value for researchers interested in studying any
      phenomena based on intermolecular interactions with ligands via molecular
      mechanics simulations. It is free and open to all at
      jorgensenresearch.com/ligpargen, and has no login requirements.

PMID- 28444341
TI  - Corrigendum.

PMID- 28444342
TI  - Harm and the Boundaries of Disease.
AB  - What is the relationship between harm and disease? Discussions of the
      relationship between harm and disease typically suffer from two shortcomings.
      First, they offer relatively little analysis of the concept of harm itself,
      focusing instead on examples of clear cases of harm such as death and
      dismemberment. This makes it difficult to evaluate such accounts in borderline
      cases, where the putative harms are less severe. Second, they assume that harm
      based accounts of disease must be understood normatively rather than
      naturalistically, in the sense that they are inherently value based. This makes
      such accounts vulnerable to more general objections of normative accounts of
      disease. Here we draw on an influential account of harm from the philosophy of
      law to develop a harm-based account of disease that overcomes both of these
      shortcomings.

PMID- 28444343
TI  - Lysolecithin as feed additive enhances collagen expression and villus length in
      the jejunum of broiler chickens.
AB  - Adding lysolecithin to feed has reportedly improved the performance of broiler
      chickens. Lysolecithin is generated by phospholipase catalyzed hydrolysis of
      lecithin. The enzymatic reaction converts various phospholipids into the
      corresponding lysophospholipids, with lysophosphatidylcholine (LPC) one of the
      primary products. Here we compared supplementation with a commercial lysolecithin
      (Lysoforte(r)) with comparable levels of highly purified LPC for effects on
      broilers. Despite no differences in weight gain during the starter period, we
      discovered a significant increase in average villus length with lysolecithin and
      an increase in villus width with purified LPC. High-throughput gene expression
      microarray analyses revealed many more genes were regulated in the epithelium of
      the jejunum by lysolecithin compared to purified LPC. The most up-regulated genes
      and pathways were for collagen, extracellular matrix, and integrins. Staining
      sections of the jejunum with Picrosirius Red confirmed the increased deposition
      of collagen fibrils in the villi of broilers fed lysolecithin, but not purified
      LPC. Thus, lysolecithin elicits gene expression in the intestinal epithelium,
      leading to enhanced collagen deposition and villus length. Purified LPC alone as
      a supplement does not mimic these responses. Feed supplementation with
      lysolecithin triggers changes in the intestinal epithelium with the potential to
      improve overall gut health and performance.

PMID- 28444344
TI  - Hydrogen Sulfide Regulates the Cytosolic/Nuclear Partitioning of Glyceraldehyde-3
      Phosphate Dehydrogenase by Enhancing its Nuclear Localization.
AB  - Hydrogen sulfide is an important signaling molecule comparable with nitric oxide
      and hydrogen peroxide in plants. The underlying mechanism of its action is
      unknown, although it has been proposed to be S-sulfhydration. This post
      translational modification converts the thiol groups of cysteines within proteins
      to persulfides, resulting in functional changes of the proteins. In Arabidopsis
      thaliana, S-sulfhydrated proteins have been identified, including the cytosolic
      isoforms of glyceraldehyde-3-phosphate dehydrogenase GapC1 and GapC2. In this
      work, we studied the regulation of sulfide on the subcellular localization of
      these proteins using two different approaches. We generated GapC1-green
      fluorescent protein (GFP) and GapC2-GFP transgenic plants in both the wild type
      and the des1 mutant defective in the l-cysteine desulfhydrase DES1, responsible
      for the generation of sulfide in the cytosol. The GFP signal was detected in the
      cytoplasm and the nucleus of epidermal cells, although with reduced nuclear
      localization in des1 compared with the wild type, and exogenous sulfide treatment
      resulted in similar signals in nuclei in both backgrounds. The second approach
      consisted of the immunoblot analysis of the GapC endogenous proteins in enriched
      nuclear and cytosolic protein extracts, and similar results were obtained. A
      significant reduction in the total amount of GapC in des1 in comparison with the
      wild type was determined and exogenous sulfide significantly increased the
      protein levels in the nuclei in both plants, with a stronger response in the wild
      type. Moreover, the presence of an S-sulfhydrated cysteine residue on GapC1 was
      demonstrated by mass spectrometry. We conclude that sulfide enhances the nuclear
      localization of glyceraldehyde-3-phosphate dehydrogenase.

PMID- 28444346
TI  - Resistant starch as a novel dietary strategy to maintain kidney health in
      diabetes mellitus.
AB  - The worldwide prevalence of diabetes mellitus is expected to reach 439 million by
      2030. Diabetes increases the risk for developing secondary complications such as
      nephropathy and cardiovascular disease, critical factors that dictate the
      survival rate of diabetes patients. Compelling evidence has indicated that the
      positive impact of fermentable carbohydrates in obesity-related diabetes is
      mediated by the production of short-chain fatty acids and the modulation of
      colonic microbiota. This review summarizes the potential implications of dietary
      resistant starch, a class of fermentable fiber, in glucose homeostasis and kidney
      health in obesity-associated diabetes and examines the mechanisms underlying the
      protective effect of resistant starch. Though extensive clinical studies are
      still warranted, replacement of simple carbohydrates with resistant starch could
      be a highly effective alternative dietary strategy to prevent secondary
      complications resulting from hyperglycemia.

PMID- 28444345
TI  - Causal evidence for task-specific involvement of the dorsomedial prefrontal
      cortex in human social cognition.
AB  - The dorsomedial prefrontal cortex (dmPFC) is a key hub of the 'social brain', but
      little is known about specific processes supported by this region. Using focal
      high-definition transcranial direct current stimulation (HD-tDCS) and a social
      cognitive battery with differing demands on self-other processing, we demonstrate
      specific involvement of the dmPFC in tasks placing high demands on self-other
      processing. Specifically, excitatory (anodal) HD-tDCS enhanced the integration of
      external information into the self for explicit higher-order socio-cognitive
      tasks across cognitive domains; i.e. visual perspective taking (VPT) and episodic
      memory. These effects were task specific, as no stimulation effects were found
      for attributing mental states from the eyes or implicit VPT. Inhibitory
      (cathodal) HD-tDCS had weaker effects in the opposite direction towards reduced
      integration of external information into the self. We thus demonstrate for the
      first time a specific and causal role of the dmPFC in integrating higher-order
      information from others/external source into that of the self across cognitive
      domains.

PMID- 28444347
TI  - Fluxomics links cellular functional analyses to whole-plant phenotyping.
AB  - Fluxes through metabolic pathways reflect the integration of genetic and
      metabolic regulations. While it is attractive to measure all the mRNAs
      (transcriptome), all the proteins (proteome), and a large number of the
      metabolites (metabolome) in a given cellular system, linking and integrating this
      information remains difficult. Measurement of metabolome-wide fluxes (termed the
      fluxome) provides an integrated functional output of the cell machinery and a
      better tool to link functional analyses to plant phenotyping. This review
      presents and discusses sets of methodologies that have been developed to measure
      the fluxome. First, the principles of metabolic flux analysis (MFA), its 'short
      time interval' version Inst-MFA, and of constraints-based methods, such as flux
      balance analysis and kinetic analysis, are briefly described. The use of these
      powerful methods for flux characterization at the cellular scale up to the organ
      (fruits, seeds) and whole-plant level is illustrated. The added value given by
      fluxomics methods for unravelling how the abiotic environment affects flux, the
      process, and key metabolic steps are also described. Challenges associated with
      the development of fluxomics and its integration with 'omics' for thorough plant
      and organ functional phenotyping are discussed. Taken together, these will
      ultimately provide crucial clues for identifying appropriate target plant
      phenotypes for breeding.

PMID- 28444348
TI  - How Physically Active Are People Following Stroke? Systematic Review and
      Quantitative Synthesis.
AB  - Background: Mobility limitations are common following stroke and frequently lead
      to poor participation in physical activity (PA). Purpose: The purpose of this
      study was to describe PA across the various stages following stroke (acute,
      subacute, and chronic). Data Sources: Searches were conducted in 5 databases.
      Study Selection: Eligible studies included participants with stroke whose PA was
      quantitatively measured for at least 4 hours in a single session. Two reviewers
      independently reviewed titles and abstracts. Data Extraction: One reviewer
      extracted data and assessed quality using the Downs and Black checklist. Weighted
      means were calculated for PA outcomes. Data Synthesis: Searches yielded 103
      eligible papers including 5306 participants aged 21 to 96 years. Devices (eg,
      activity monitors) were used in 73 papers, and behavioral mapping (observational
      monitoring) in 30. Devices show that people with stroke took on average 5535
      steps per day (n = 406, 10 studies) in the subacute phase and 4078 steps (n =
      1280, 32 studies) in the chronic phase. Average daily walking duration (%
      measured time) was higher in the chronic phase (9.0%, n = 100) than subacute
      (1.8%, n = 172), and sedentary time was >78% regardless of time post stroke.
      Acute data were lacking for these variables. Matched healthy individuals took an
      average of 8338 steps per day (n = 129). Behavioral mapping showed time in bed
      was higher in the acute than subacute phase (mean 45.1% versus 23.8%), with
      similar time spent sitting (mean 37.6% versus 32.6%). Limitations: Limitations of
      this review include not pooling data reported as medians. Conclusions: Physical
      activity levels do not meet guidelines following stroke. Time spent inactive and
      sedentary is high at all times. Increasing PA and developing standardized
      activity targets may be important across all stages of stroke recovery.

PMID- 28444349
TI  - Adult Children's Education and Physiological Dysregulation Among Older Parents.
AB  - Objectives: Despite growing awareness that children's education benefits the
      health of older parents, the underlying mechanisms of this relationship are not
      well-understood. We investigated (a) the associations between children's
      education and biological functioning of parents, (b) psychosocial and behavioral
      factors that explain the associations, and (c) gendered patterns in the
      associations. Methods: Using longitudinal data from a nationally representative
      sample of older Taiwanese, we performed mediation analysis of the association
      between adult children's education and physiological dysregulation of their
      parents. Results: Offspring's schooling is inversely associated with parental
      inflammation after controlling for parental socioeconomic status and baseline
      health. Parents who have well-educated children report higher social standing and
      life satisfaction, experience fewer stressful events, and are more likely to
      engage in healthy behaviors related to smoking and diet. These factors moderately
      attenuate the associations between children's education and parental
      inflammation. There is no conclusive evidence that mothers and fathers benefit
      differently from having well-educated children. Discussion: Parents who devote
      family and personal resources to their offspring's schooling may have better
      biological profiles in later life. Well-educated children may promote their
      parents' wellbeing by strengthening perceived social status, reducing exposure to
      stressors, and encouraging a healthy lifestyle.

PMID- 28444350
TI  - Reliability, Validity, and Minimal Detectable Change of Four-Step Stair Climb
      Power Test in Community-Dwelling Older Adults.
AB  - Background: Stair climb power is an important clinical measure of lower-extremity
      power. The stair climb power test (SCPT) was validated by requiring individuals
      to climb a full flight of stairs. A 4-step SCPT (4SCPT) would be more clinically
      feasible and easier to perform, yet its reliability and validity are unknown.
      Objective: To evaluate reliability, validity, and minimal detectable change of
      4SCPT among community-dwelling older adults. Design: This study is a cross
      sectional analysis of baseline data from a clinical trial. Methods: Fifty older
      adults >=65 years of age, at risk for mobility decline, consented to participate
      in this ancillary study. Test-retest reliability was derived from 2 measurements
      within each participant measured by a single assessor. Pearson correlation
      analyses among leg power measures (4SCPT, SCPT, single leg press power at 40% and
      70% of the 1-repetition maximum [SLP40, SLP70]) were performed. Separate
      multivariate linear regressions were conducted evaluating the associations
      between each leg power measure and 2 mobility outcomes, the Short Physical
      Performance Battery (SPPB) and habitual gait speed (HGS). Minimal detectable
      change was based on a 90% confidence interval (MDC 90 ). Results: The 4SCPT had
      excellent test-retest reliability (ICC(2,1) = 0.951), and strong correlation with
      SCPT, SLP40, and SLP70 ( r = 0.85-0.96). The 4SCPT explained a greater amount of
      variance in the SPPB (R 2 = 0.31) than other leg power measurements (R 2 = 0.23
      0.25). The 4SCPT (R 2 = 0.41) and SCPT (R 2 = 0.42) described equivalent amounts
      of variance in HGS, and greater than that with SLP40 (R 2 = 0.28) and SLP70 (R 2
      = 0.30). The MDC 90 for 4SCPT was 44.0 watts. Limitations: This was a cross
      sectional analysis within a small, nonrepresentative sample. Interrater
      reliability was not evaluated. Conclusions: The 4SCPT shows scientific promise as
      a valid and reliable leg power measurement among community-dwelling older adults.

PMID- 28444353
TI  - Early Identification of Pregnant Women at Risk for Preeclampsia: USPSTF
      Recommendations on Screening for Preeclampsia.

PMID- 28444351
TI  - Comparative genomic analysis of SET domain family reveals the origin, expansion,
      and putative function of the arthropod-specific SmydA genes as histone modifiers
      in insects.
AB  - The SET domain is an evolutionarily conserved motif present in histone lysine
      methyltransferases, which are important in the regulation of chromatin and gene
      expression in animals. In this study, we searched for SET domain-containing genes
      (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying
      out this experiment to understand the evolutionary history by which SET domains
      have evolved in insects. Phylogenetic and ancestral state reconstruction analysis
      revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to
      arthropod animals and specifically diversified during insect evolution.
      Considering that pseudogenization is the most probable fate of the new emerging
      gene copies, we provided experimental and evolutionary evidence to demonstrate
      their essential functions. Fluorescence in situ hybridization analysis and in
      vitro methyltransferase activity assays showed that the SmydA-2 gene was
      transcriptionally active and retained the original histone methylation activity.
      Expression knockdown by RNA interference significantly increased mortality,
      implying that the SmydA genes may be essential for insect survival. We further
      showed predominantly strong purifying selection on the SmydA gene family and a
      potential association between the regulation of gene expression and insect
      phenotypic plasticity by transcriptome analysis. Overall, these data suggest that
      the SmydA gene family retains essential functions that may possibly define novel
      regulatory pathways in insects. This work provides insights into the roles of
      lineage-specific domain duplication in insect evolution.

PMID- 28444352
TI  - Preeclampsia and Hypertension: Courting a Long While: Time to Make It Official.

PMID- 28444354
TI  - Easy-Assessment of Levofloxacin and Minocycline in Relevant Biomimetic Media by
      HPLC-UV Analysis.
AB  - Simple, economic and environmental friendly high-performance liquid
      chromatography methods for levofloxacin and minocycline quantification in
      biomimetic media were developed and validate including their stability at body
      temperature, an often neglected evaluation parameter. Both methods are similar
      only differing in the wavelength setting, i.e., for levofloxacin and minocycline
      quantification the UV detection was set at 284 and at 273 nm, respectively. The
      separation of both antibiotics was achieved using a reversed-phase column and a
      mobile phase consisting of acetonitrile and water (15:85) with 0.6%
      triethylamine, adjusted to pH 3. As an internal standard for levofloxacin
      quantification, minocycline was used and vice versa. The calibration curves for
      both methods were linear (r = 0.99) over a concentration range of 0.3-16 MUg/mL
      and 0.5-16 MUg/mL for levofloxacin and minocycline, respectively, with precision,
      accuracy and recovery in agreement with international guidelines requirement.
      Levofloxacin revealed stability in all media and conditions, including at 37
      degrees C, with exception to freeze-thaw cycle conditions. Minocycline presented
      a more accentuated degradation profile over prolonged time courses, when compared
      to levofloxacin. Reported data is of utmost interest for pharma and biomaterials
      fields regarding the research and development of new local drug-delivery-systems
      containing either of these two antibiotics, namely when monitoring the in vitro
      release studies of those systems.

PMID- 28444355
TI  - Improvement in Obstructive Sleep Apnea With Weight Loss is Dependent on Body
      Position During Sleep.
AB  - Study Objectives: Weight loss fails to resolve obstructive sleep apnea (OSA) in
      most patients; however, it is unknown as to whether weight loss differentially
      affects OSA in the supine compared with nonsupine sleeping positions. We aimed to
      determine if weight loss in obese patients with OSA results in a greater
      reduction in the nonsupine apnea/hypopnea index (AHI) compared with the supine
      AHI, thus converting participants into supine-predominant OSA. Methods: Post hoc
      analysis of data from a randomized controlled trial assessing the effect of
      weight loss (bariatric surgery vs. medical weight loss) on OSA in 60 participants
      with obesity (body mass index: >35 and <55) with recently diagnosed (<6 months)
      OSA and AHI of >= 20 events/hour. Patients were randomized to very low calorie
      diet with regular review (n = 30) or to laproscopic adjustable gastric banding (n
      = 30) with follow-up sleep study at 2 years. Results: Eight of 37 (22%) patients
      demonstrated a normal nonsupine AHI (<5 events/hour) on follow-up compared to
      0/37 (0%) patients at baseline (p = .003). These patients were younger (40.0 +/-
      9.6 years vs. 48.4 +/- 6.5 years, p = .007) and lost significantly more weight
      (percentage weight change -23.0 [-21.0 to -31.6]% vs. -6.9 [1.9 to -17.4], p =
      .001). The percentage change in nonsupine AHI was greater than the percentage
      change in supine AHI (-54.0 [-15.4 to -87.9]% vs -33.1 [-1.8 to -69.1]%, p =
      .05). However, the change in absolute nonsupine AHI was not related to change in
      absolute supine AHI (p = .23). Conclusions: Following weight loss, a significant
      proportion (22%) of patients with obesity have normalization of the nonsupine
      AHI. For these patients, supine sleep avoidance may cure their OSA.

PMID- 28444356
TI  - Long-term effects of drought on tree-ring growth and carbon isotope variability
      in Scots pine in a dry environment.
AB  - Drought frequency is increasing in many parts of the world and may enhance tree
      decline and mortality. The underlying physiological mechanisms are poorly
      understood, however, particularly regarding chronic effects of long-term drought
      and the response to increasing temperature and vapor pressure deficit (VPD). We
      combined analyses of radial growth and stable carbon isotope ratios (delta13C) in
      tree rings in a mature Scots pine (Pinus sylvestris L.) forest over the 20th
      century to elucidate causes of tree mortality in one of the driest parts of the
      European Alps (Pfynwald, Switzerland). We further compared trees that have
      recently died with living trees in a 10-year irrigation experiment, where annual
      precipitation was doubled. We found a sustained growth increase and immediate
      depletion of delta13C values for irrigated trees, indicating higher stomatal
      conductance and thus indeed demonstrating that water is a key limiting factor for
      growth. Growth of the now-dead trees started declining in the mid-1980s, when
      both mean temperature and VPD increased strongly. But growth of these trees was
      reduced to some extent already several decades earlier, while intrinsic water-use
      efficiency derived from delta13C values was higher. This indicates a more
      conservative water-use strategy compared with surviving trees, possibly at the
      cost of low carbon uptake and long-term reduction of the needle mass. We observed
      reduced climatic sensitivity of raw tree-ring delta13C for the now-dead in
      contrast to surviving trees, indicating impaired stomatal regulation, although
      this difference between the tree groups was smaller after detrending the data.
      Higher autocorrelation and a lower inter-annual delta13C variability of the now
      dead trees further indicates a strong dependence on (low) carbon reserves. We
      conclude that the recent increase in atmospheric moisture demand in combination
      with insufficient soil water supply was the main trigger for mortality of those
      trees that were weakened by long-term reduced carbon uptake.

PMID- 28444358
TI  - Primary adrenal and chest wall tuberculosis presenting as an adrenal crisis.

PMID- 28444357
TI  - Co-ordinated Regulations of mRNA Synthesis and Decay during Cold Acclimation in
      Arabidopsis Cells.
AB  - Plants possess a cold acclimation system to acquire freezing tolerance through
      pre-exposure to non-freezing low temperatures. The transcriptional cascade of C
      repeat-binding factors (CBFs)/dehydration response element-binding factors
      (DREBs) is considered a major transcriptional regulatory pathway during cold
      acclimation. However, little is known regarding the functional significance of
      mRNA stability regulation in the response of gene expression to cold stress. The
      actual level of individual mRNAs is determined by a balance between mRNA
      synthesis and degradation. Therefore, it is important to assess the regulatory
      steps to increase our understanding of gene regulation. Here, we analyzed
      temporal changes in mRNA amounts and half-lives in response to cold stress in
      Arabidopsis cell cultures based on genome-wide analysis. In this mRNA decay array
      method, mRNA half-life measurements and microarray analyses were combined. In
      addition, temporal changes in the integrated value of transcription rates were
      estimated from the above two parameters using a mathematical approach. Our
      results showed that several cold-responsive genes, including Cold-regulated 15a,
      were relatively destabilized, whereas the mRNA amounts were increased during cold
      treatment by accelerating the transcription rate to overcome the destabilization.
      Considering the kinetics of mRNA synthesis and degradation, this apparently
      contradictory result supports that mRNA destabilization is advantageous for the
      swift increase in CBF-responsive genes in response to cold stress.

PMID- 28444359
TI  - Realistic dosimetry for studies on biological responses to X-rays and gamma-rays.
AB  - A calibration coefficient R (= DA/DE) for photons was employed to characterize
      the photon dose in radiobiological experiments, where DA was the actual dose
      delivered to cells and DE was the dose recorded by an ionization chamber. R was
      determined using the Monte Carlo N-Particle version 5 (MCNP-5) code. Photons with
      (i) discrete energies, and (ii) continuous-energy distributions under different
      beam conditioning were considered. The four studied monoenergetic photons had
      energies E = 0.01, 0.1, 1 and 2 MeV. Photons with E = 0.01 MeV gave R values
      significantly different from unity, while those with E > 0.1 MeV gave R ~ 1.
      Moreover, R decreased monotonically with increasing thickness of water medium
      above the cells for E = 0.01, 1 or 2 MeV due to energy loss of photons in the
      medium. For E = 0.1 MeV, the monotonic pattern no longer existed due to the dose
      delivered to the cells by electrons created through the photoelectric effect
      close to the medium-cell boundary. The continuous-energy distributions from the X
      Rad 320 Biological Irradiator (voltage = 150 kV) were also studied under three
      different beam conditions: (a) F0: no filter used, (b) F1: using a 2 mm-thick Al
      filter, and (c) F2: using a filter made of (1.5 mm Al + 0.25 mm Cu + 0.75 mm Sn),
      giving mean output photon energies of 47.4, 57.3 and 102 keV, respectively. R
      varied from ~1.04 to ~1.28 for F0, from ~1.13 to ~1.21 for F1, and was very close
      to unity for F2.

PMID- 28444360
TI  - Role of Early Onset Neutropenia in Development of Candidemia in Premature
      Infants.
AB  - Background: The aim of the study was to assess the effect of early-onset
      neutropenia (EON) on the development of candidemia in premature infants and
      evaluate other risk factors. Materials and Methods: This prospective study was
      carried out in a neonatal intensive care unit of Cairo University Hospital. Fifty
      neutropenic premature infants were matched to 50 non-neutropenics. Subjects were
      then regrouped into candidemics and non-candidemics to study other risk factors
      such as central venous catheters, mechanical ventilation, parenteral nutrition,
      drugs as corticosteroids and others. Candidemia was assessed by Bactec and then
      seminested polymerase chain reaction for culture negatives. Results: Candidemia
      developed in 28 neutropenic preterms and in 8 non-neutropenics (odds ratio  =
      6.68, 95% confidence interval = 2.61-17.1, p <0.001). Risk factors for invasive
      fungal infection in univariate analysis included bacterial septicemia, mechanical
      ventilation, parenteral nutrition and steroid therapy. Independent predictors of
      candidemia in multivariate regression analysis included EON, mechanical
      ventilation and steroid therapy. Conclusion: EON is an independent risk factor
      for candidemia in premature infants.

PMID- 28444361
TI  - Time for an immunisation paradigm shift.

PMID- 28444362
TI  - Burden of Severe Acute Malnutrition in under-five Children (2-59 Months) Admitted
      in a Tertiary Care Hospital of Delhi.
AB  - Objective: The aim of the present study is to assess the burden of severe acute
      malnutrition (SAM) and other malnutrition in a tertiary care hospital in Delhi.
      Methods: All patients aged 2-59 months admitted from August 2012 to July 2014
      were screened for malnutrition by anthropometry using standard techniques, and
      SAM was diagnosed as per guidelines [1, 2]. Results: During the study period,
      4520 children of age 2-59 months were admitted and complete data of 4354 children
      were available, which were analysed. Of these, 50.4% were underweight, 44.6% were
      stunted, 33.5% were wasted, 0.76% had oedematous malnutrition and 18.3% had SAM.
      Of all patients with SAM, 80% were <24 months old, with 54.1% males and 45.9%
      females. Moderate acute malnutrition was present in 21.4%. Associated co
      morbidities were diarrhoea or respiratory infection or both. Conclusion:
      Hospitals of Delhi have a high load of complicated SAM and need adequate
      infrastructure and facilities for management of these children.

PMID- 28444363
TI  - SGH: stress or strain gradient hypothesis? Insights from an elevation gradient on
      the roof of the world.
AB  - Background and Aims: The stress gradient hypothesis (SGH), the view that
      competition prevails in undisturbed and productive environments, and shifts to
      facilitation in disturbed or stressful environments, has become a central
      paradigm in ecology. However, an alternative view proposes that the relationship
      between biotic interactions and environmental severity should be unimodal instead
      of monotonic. Possible causes of discrepancies between these two views were
      examined in the high elevation desert of the arid Trans-Himalayas. Methods: A
      putative nurse species and its associated plant community was surveyed over its
      entire elevation range, spanning from alpine to desert vegetation belts. The
      results were analysed at the community level (vegetation cover and species
      richness), considering the distinction between the intensity and the importance
      of biotic interactions. Interactions at the species level (pairwise interactions)
      were also considered, i.e. the variation of biotic interactions within the niche
      of a species, for which the abundance (species cover) and probability of
      occurrence (presence/absence) for the most widespread species along the gradient
      were distinguished. Key Results: Overall, facilitation was infrequent in our
      study system; however, it was observed for the two most widespread species. At
      the community level, the intensity and importance of biotic interactions showed a
      unimodal pattern. The departure from the prediction of the SGH happened abruptly
      where the nurse species entered the desert vegetation belt at the lowest
      elevation. This abrupt shift was attributed to the turnover of species with
      contrasting tolerances. At the species level, however, facilitation increased
      consistently as the level of stress increases and individuals deviate from their
      optimum (increasing strain). Conclusion: While the stress gradient hypothesis was
      not supported along our elevation gradient at the community level, the strain
      gradient hypothesis, considering how species perceive the ambient level of stress
      and deviate from their optimum, provided a parsimonious explanation for the
      outcome of plant-plant interactions at both scales.

PMID- 28444364
TI  - Effect of rituximab on the progression of rheumatoid arthritis-related
      interstitial lung disease: 10 years' experience at a single centre.
AB  - Objective: To evaluate the effect of rituximab (RTX) in patients with RA-related
      interstitial lung disease (RA-ILD) and identify factors associated with outcome
      after treatment. Methods: An observational study of patients with RA-ILD was
      conducted from a cohort of RTX-treated RA patients in a single centre for >10
      years. Progression was defined by any of the following: a decrease of pre-RTX
      forced vital capacity (FVC) >10% or diffusion capacity of carbon monoxide (DLCO)
      >15% predicted, worsening of the ILD score or death from progressive ILD.
      Results: Of 700 RA patients treated with RTX, 56 had RA-ILD (prevalence = 8%).
      After RTX, new ILD was diagnosed in 3/700 patients (incidence = 0.4%). Data for
      lung assessment were available for 44/56 patients. The median relative change pre
      and post-RTX for FVC were -2.4% and +1.2% ( P = 0.025) and for DLCO were -4.4%
      and -1.3% ( P = 0.045). Post-RTX, 23/44 (52%) were stable and 7/44 (16%) had
      improved. Of the 14 (32%) with ILD that progressed, 9/56 (16%) were deaths due to
      progressive ILD. Factors associated with ILD progression were radiologic pattern
      of usual interstitial pneumonia, a previous history of lung progression and pre
      RTX DLCO <46% predicted. Of those whose ILD progressed, 11/14 (79%) had severe
      ILD before RTX [median DLCO 42% predicted (interquartile range 41-49)].
      Conclusion: In this cohort of patients where RTX was given for arthritis, most
      patients with ILD pre-RTX remained stable/improved after treatment over a
      prolonged follow-up period. Patients who deteriorated/died had the most severe
      ILD pre-RTX, suggesting the drug was not contributory. RTX appears to be an
      acceptable therapeutic choice for patients with RA-ILD and further studies are
      warranted.

PMID- 28444365
TI  - Evaluation of Attractants for Monitoring Drosophila suzukii (Diptera:
      Drosophilidae).
AB  - Drosophila suzukii Matsumura is an economically important pest of soft and small
      fruit crops. Unlike other drosophilid flies, D. suzukii is capable of infesting
      ripe and partially ripe fruit, which poses a significant pest management
      challenge, as there is no tolerance for infested or damaged fruit in the
      marketplace. As a result, producers in many regions rely on calendar-scheduled
      insecticide applications for D. suzukii management. In order to develop an
      integrated pest management approach, better tools for monitoring adult fly
      populations are needed. Over two growing seasons in southern Ontario, we
      evaluated three commercial (Pherocon SWD dual-lure, Suzukii Trap, and Scentry
      Lure) and two homemade baits (apple cider vinegar and yeast + sugar water) for
      their ability to capture D. suzukii in raspberry and highbush blueberry fields.
      In general, commercial attractants captured D. suzukii earlier in the growing
      season and in greater numbers, with fewer nontarget captures, compared with
      homemade baits. Scentry Lure tended to perform better than other attractants,
      capturing D. suzukii earlier and in larger numbers during peak harvest. Pherocon
      SWD dual-lure was highly specific to D. suzukii. The combination of Scentry Lure
      with Suzukii Trap had possible synergistic effects, as numbers of D. suzukii
      captured to the combined treatment were more than additive. Using commercial
      attractants improves D. suzukii monitoring and will allow growers to improve the
      timing of insecticide applications with D. suzukii activity in the field.

PMID- 28444367
TI  - Corrigendum to: Affective facilitation of early visual cortex during rapid
      picture presentation at 6 and 15 Hz.

PMID- 28444366
TI  - Intraoperative air leak measured after lobectomy is associated with postoperative
      duration of air leak.
AB  - OBJECTIVES: To verify the association between the air leak objectively measured
      intraoperatively (IAL) using the ventilator and the air leak duration after
      pulmonary lobectomy. METHODS: Prospective analysis on 111 patients submitted to
      pulmonary lobectomy (33 by video-assisted thoracic surgery). After resection,
      objective assessment of air leak (in milliliter per minute) was performed before
      closure of the chest by measuring the difference between a fixed inspired and
      expired volume, using a tidal volume of 8 ml/kg, a respiratory rate of 10 and a
      positive-end expiratory pressure of 5 cmH2O. A multivariable analysis was
      performed for identifying factors associated with duration of postoperative air
      leak. RESULTS: Average IAL was 158 ml/min (range 0-1500 ml/min). The best cut-off
      (receiver-operating characteristics analysis) associated with air leak longer
      than 5 days was 500 ml/min. Nine patients had IAL >500 ml/min (8%). They had a
      longer duration of postoperative air leak compared with those with a lower IAL
      (mean values, 10.1 days, SD 8.8 vs 1.5 days, SD 4.9 P < 0.001). The following
      variables remained associated with days of air leak duration after multivariable
      regression: left side resection (P = 0.018), upper site resection (P = 0.031) and
      IAL >500 ml/min (P < 0.001). The following equation estimating the days of air
      leak duration was generated: 1.7 + 2.4 * left side + 2.2 * upper site + 8.8 * IAL
      >500. CONCLUSIONS: The air leak measurement using the ventilator parameters after
      lung resection may assist in estimating the risk of postoperative prolonged air
      leak. An IAL > 500 ml/min may warrant the use of intraoperative preventative
      measures, particularly after video-assisted thoracic surgery lobectomy where a
      submersion test is often unreliable.

PMID- 28444368
TI  - Simultaneous Targeting of Multiple Gene Homeologs to Alter Seed Oil Production in
      Camelina sativa.
AB  - The ability to transform Camelina sativa easily with biosynthetic enzymes derived
      from other plants has made this oil seed crop an ideal platform for the
      production of unusual lipids valuable for different applications. However, in
      addition to expressing transgenic enzymes, the suppression of endogenous enzyme
      activity to reduce competition for common substrates or cofactors is also
      required to enhance the production of target compounds. As camelina possesses a
      relatively undifferentiated hexaploid genome, up to three gene homeologs can code
      for any particular enzymatic activity, complicating efforts to alter endogenous
      biosynthetic pathways. New genome editing technologies, such as that offered by
      the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR
      associated protein) system, offer the capability to introduce mutations into
      specifically targeted genomic sites. Here, by using a carefully designed guide
      RNA identical to all three homeologs, we demonstrate the ability of the
      CRISPR/Cas genome editing system to introduce mutations in all three CsDGAT1 or
      CsPDAT1 homeologous genes important for triacylglycerol (TAG) synthesis in
      developing seeds. Sequence analysis from transgenic T1 plants revealed that each
      CsDGAT1 or each CsPDAT1 homeolog was altered by multiple mutations, resulting in
      a genetic mosaic in the plants. Interestingly, seed harvested from both CsDGAT1-
      and CsPDAT1-targeted lines was often shrunken and wrinkled. Further, lipid
      analysis revealed that many lines produced seed with reduced oil content and
      altered fatty acid composition, consistent with the role of the targeted genes in
      seed oil biosynthesis. The CRISPR/Cas system therefore represents a useful method
      to alter endogenous biosynthetic pathways efficiently in polyploid species such
      as camelina.

PMID- 28444369
TI  - Three-dimensional intracellular structure of a whole rice mesophyll cell observed
      with FIB-SEM.
AB  - Background and Aims: Ultrathin sections of rice leaf blades observed two
      dimensionally using a transmission electron microscope (TEM) show that the
      chlorenchyma is composed of lobed mesophyll cells, with intricate cell
      boundaries, and lined with chloroplasts. The lobed cell shape and chloroplast
      positioning are believed to enhance the area available for the gas exchange
      surface for photosynthesis in rice leaves. However, a cell image revealing the
      three-dimensional (3-D) ultrastructure of rice mesophyll cells has not been
      visualized. In this study, a whole rice mesophyll cell was observed using a
      focused ion beam scanning electron microscope (FIB-SEM), which provides many
      serial sections automatically, rapidly and correctly, thereby enabling 3-D cell
      structure reconstruction. Methods: Rice leaf blades were fixed chemically using
      the method for conventional TEM observation, embedded in resin and subsequently
      set in the FIB-SEM chamber. Specimen blocks were sectioned transversely using the
      FIB, and block-face images were captured using the SEM. The sectioning and
      imaging were repeated overnight for 200-500 slices (each 50 nm thick). The
      resultant large-volume image stacks ( x = 25 MUm, y = 25 MUm, z = 10-25 MUm)
      contained one or two whole mesophyll cells. The 3-D models of whole mesophyll
      cells were reconstructed using image processing software. Key Results: The
      reconstructed cell models were discoid shaped with several lobes around the cell
      periphery. The cell shape increased the surface area, and the ratio of surface
      area to volume was twice that of a cylinder having the same volume. The
      chloroplasts occupied half the cell volume and spread as sheets along the cell
      lobes, covering most of the inner cell surface, with adjacent chloroplasts in
      close contact with each other. Conclusions: Cellular and sub-cellular
      ultrastructures of a whole mesophyll cell in a rice leaf blade are demonstrated
      three-dimensionally using a FIB-SEM. The 3-D models and numerical information
      support the hypothesis that rice mesophyll cells enhance their CO 2 absorption
      with increased cell surface and sheet-shaped chloroplasts.

PMID- 28444371
TI  - Neural Correlates of Both Perception and Memory for Objects in the Rodent
      Perirhinal Cortex.
AB  - Despite its anatomical positioning as an interface between the perceptual and
      memory systems, the perirhinal cortex (PER) has long been considered dedicated
      for object recognition memory. Whether the PER is also involved in object
      perception has been intensely debated in recent studies, but physiological
      evidence has been lacking. We recorded single units from the PER while the rat
      made categorical responses immediately after sampling a visual object as the
      originally learned objects were ambiguously morphed to varying degrees. Some
      neurons in the PER  changed their firing rates monotonically following the
      gradual changes across the morphed objects as if they coded perceptual changes of
      the object stimuli. However, other neurons abruptly changed their firing rates
      according to the response categories associated with the morphed objects,
      seemingly responding to the learned relationships between the stimulus and its
      associated choice response. The gradual and abrupt changes in object-tuning
      properties were also found at the neural population level. Furthermore, the
      object-associated tuning characteristics of neurons in the PER were more readily
      observable in correct trials than in error trials. Our findings suggest that
      neurons in the PER represent perceptual details of an object in addition to its
      mnemonic identity.

PMID- 28444370
TI  - Identification of HDA15-PIF1 as a key repression module directing the
      transcriptional network of seed germination in the dark.
AB  - Light is a major external factor in regulating seed germination. Photoreceptor
      phytochrome B (PHYB) plays a predominant role in promoting seed germination in
      the initial phase after imbibition, partially by repressing phytochrome
      interacting factor1 (PIF1). However, the mechanism underlying the PHYB-PIF1
      mediated transcription regulation remains largely unclear. Here, we identified
      that histone deacetylase15 (HDA15) is a negative component of PHYB-dependent seed
      germination. Overexpression of HDA15 in Arabidopsis inhibits PHYB-dependent seed
      germination, whereas loss of function of HDA15 increases PHYB-dependent seed
      germination. Genetic evidence indicated that HDA15 acts downstream of PHYB and
      represses seed germination dependent on PIF1. Furthermore, HDA15 interacts with
      PIF1 both in vitro and in vivo. Genome-wide transcriptome analysis revealed that
      HDA15 and PIF1 co-regulate the transcription of the light-responsive genes
      involved in multiple hormonal signaling pathways and cellular processes in
      germinating seeds in the dark. In addition, PIF1 recruits HDA15 to the promoter
      regions of target genes and represses their expression by decreasing the histone
      H3 acetylation levels in the dark. Taken together, our analysis uncovered the
      role of histone deacetylation in the light-regulated seed germination process and
      identified that HDA15-PIF1 acts as a key repression module directing the
      transcription network of seed germination.

PMID- 28444373
TI  - Plasticity of the Right-Lateralized Cognitive Reserve Network in Ageing.
AB  - Cognitive reserve (CR) is the phenomenon where older adults with more cognitively
      stimulating environments show less age-related cognitive decline. The right
      lateralized fronto-parietal network has been proposed to significantly contribute
      to CR and visual attention in ageing. In this study we tested whether plasticity
      of this network may be harnessed in ageing.We assessed CR and parameters of
      visual attention capacity in older adults. Transcranial direct current
      stimulation (tDCS) was employed to increase right fronto-parietal activity during
      a lateralized whole-report task. At baseline, older adults with greater CR showed
      a stronger hemifield asymmetry in processing speed towards the left visual-field,
      indicative of stronger involvement of the right hemisphere in these individuals.
      Correspondingly, processing speed improved during right prefrontal tDCS. Older
      adults with lower levels of CR showed tDCS-related improvements in processing
      speed in the left but not right hemifield: thus tDCS temporarily altered their
      processing speed asymmetry to resemble that of their high reserve peers.The
      finding that stronger right hemisphere involvement is related to CR supports
      Robertson's theory. Furthermore, preserved plasticity within the right prefrontal
      cortex in older adults suggests this is a viable target area to improve visual
      processing speed, a hallmark of age-related decline.

PMID- 28444374
TI  - MEASUREMENT OF NEUTRON AMBIENT DOSE EQUIVALENT IN PROTON RADIOTHERAPY WITH LINE
      SCANNING AND WOBBLING MODE TREATMENT SYSTEM.
AB  - The primary objective of this study was to measure secondary neutron dose during
      proton therapy using a detector that covers the entire neutron energy range
      produced in proton therapy. We analyzed and compared the neutron dose during
      proton treatment with passive scattering and line scanning. The neutron ambient
      dose equivalents were measured with a 190 MeV wobbling and line-scanning proton
      beam. The center of a plastic water phantom (30 * 30 * 60 cm3) was placed at the
      isocenter. A Wide-Energy Neutron Detection Instrument (WENDI-2) was located 1m
      from the isocenter at four different angles (0 degrees , 45 degrees , 90 degrees 
      and 135 degrees ). Both wobbling and line-scanning modes of a multipurpose and
      pencil beam scanning dedicated nozzles were used to obtain a spread-out Bragg
      peak with 10-cm-width for the measurements. The ambient dose equivalent H*(10)
      value was normalized by the proton therapeutic dose at the isocenter. For
      wobbling mode and line-scanning mode, the highest H*(10) values were 1.972 and
      0.099 mSv/Gy, respectively. We successfully measured the neutron ambient dose
      equivalents at six positions generated by a 190 MeV proton beam using wobbling
      and line-scanning mode with the WENDI-2. These reference data could be used for
      neutron dose reduction methods and other analysis for advanced proton treatment
      in the near future.

PMID- 28444372
TI  - Quantifying the Number of Independent Organelle DNA Insertions in Genome
      Evolution and Human Health.
AB  - Fragments of organelle genomes are often found as insertions in nuclear DNA.
      These fragments of mitochondrial DNA (numts) and plastid DNA (nupts) are
      ubiquitous components of eukaryotic genomes. They are, however, often edited out
      during the genome assembly process, leading to systematic underestimation of
      their frequency. Numts and nupts, once inserted, can become further fragmented
      through subsequent insertion of mobile elements or other recombinational events
      that disrupt the continuity of the inserted sequence relative to the genuine
      organelle DNA copy. Because numts and nupts are typically identified through
      sequence comparison tools such as BLAST, disruption of insertions into smaller
      fragments can lead to systematic overestimation of numt and nupt frequencies.
      Accurate identification of numts and nupts is important, however, both for better
      understanding of their role during evolution, and for monitoring their
      increasingly evident role in human disease. Human populations are polymorphic for
      141 numt loci, five numts are causal to genetic disease, and cancer genomic
      studies are revealing an abundance of numts associated with tumor progression.
      Here, we report investigation of salient parameters involved in obtaining
      accurate estimates of numt and nupt numbers in genome sequence data. Numts and
      nupts from 44 sequenced eukaryotic genomes reveal lineage-specific differences in
      the number, relative age and frequency of insertional events as well as lineage
      specific dynamics of their postinsertional fragmentation. Our findings outline
      the main technical parameters influencing accurate identification and frequency
      estimation of numts in genomic studies pertinent to both evolution and human
      health.

PMID- 28444375
TI  - Evaluation of the alpha-amylase activity as an indicator of pasteurization
      efficiency and microbiological quality of liquid whole eggs.
AB  - In order to evaluate the efficiency of the pasteurization process in liquid whole
      eggs, an UV/visible spectrophotometric method was developed and validated for the
      assessment of alpha-amylase activity. Samples were collected from 30 lots of raw
      eggs (n = 30) and divided into three groups: one was reserved for analysis of the
      raw eggs, the second group was pasteurized at 61.1 degrees C for 3.5 minutes (n =
      30), and the third group was pasteurized at 64.4 degrees C for 2.5 minutes (n =
      30). In addition to assessing alpha-amylase activity, the microbiological quality
      of the samples was also evaluated by counting total and thermotolerant coliforms,
      mesophilic aerobic microorganisms, Staphylococcus spp., and Salmonella spp. The
      validated spectrophotometric method demonstrated linearity, with a coefficient of
      determination (R2) greater than 0.99, limits of detection (LOD) and
      quantification (LOQ) of 0.48 mg kg-1 and 1.16 mg kg-1, respectively, and
      acceptable precision and accuracy with relative standard deviation (RSD) values
      of less than 10% and recovery rates between 98.81% and 105.40%. The results for
      alpha-amylase activity in the raw egg samples showed high enzyme activity due to
      near-complete hydrolysis of the starch, while in the eggs pasteurized at 61.1
      degrees C, partial inactivation of the enzyme was observed. In the samples of
      whole eggs pasteurized at 64.4 degrees C, starch hydrolysis did not occur due to
      enzyme inactivation. The results of the microbiological analyses showed a
      decrease (P < 0.0001) in the counts for all the studied microorganisms and in the
      frequency of Salmonella spp. in the pasteurized egg samples according to the two
      binomials under investigation, compared to the raw egg samples, which showed high
      rates of contamination (P < 0.0001). After pasteurization, only one sample
      (3.33%) was positive for Salmonella spp., indicating failure in the
      pasteurization process, which was confirmed by the alpha-amylase test. It was
      concluded that the validated methodology for testing alpha-amylase activity is
      adequate for assessing the efficiency of the pasteurization process, and that the
      time-temperature binomial used in this study is suitable to produce pasteurized
      eggs with high microbiological quality.

PMID- 28444376
TI  - Management of patients with transposition of the great arteries and intact
      interventricular septum.

PMID- 28444377
TI  - Primary chondrosarcoma of the trachea with extensive extraluminal growth.
AB  - Primary chondrosarcoma of the trachea is an extremely rare non-epithelial
      neoplasm with only few cases published in the literature. We present a rare case
      of tracheal chondrosarcoma with extensive extraluminal growth. We operated a
      patient with obstructive tumour of the upper third of the trachea via partial
      sternotomy. Before surgery, a Hanarostent was put into the trachea to treat a
      life-threatening stenosis. Postoperative period was uneventful. We discuss the
      incidence, clinical presentation and treatment options in patients with rare
      tracheal tumours. In some cases, a multidisciplinary approach (endoscopic
      intervention followed by surgical resection) is an effective treatment tool.

PMID- 28444378
TI  - How Efficient Is Apis cerana (Hymenoptera: Apidae) in Pollinating Cabbage,
      Brassica oleracea var. capitata? Pollination Behavior, Pollinator Effectiveness,
      Pollinator Requirement, and Impact of Pollination.
AB  - Cabbage is a cross-pollinated crop because of sporophytic self-incompatibility,
      and honey bees play an important role in its pollination. Though Asian honey
      bees, Apis cerana F., are used in pollination of cabbage, the rate of visitation,
      behavior, pollinator efficacy, and impact on seed-set are to be determined. Apis
      cerana occupy a share of 19.18% of all the flower visitors of cabbage in natural
      habitat of North Western Indian Himalayas. Pollination behavior in terms of peak
      activity, flowers processed per unit time, time spent per flower, and time spent
      in search of flowers are studied separately for both pollen and nectar foragers.
      Pollinator effectiveness as measured by seed set in flowers excluded from bee
      visitation, single bee visit, and unrestricted pollinator visits was 0.11.
      Studies on the impact of A. cerana bee pollination in cabbage seed production
      revealed an increase of 17.28% in siliqua per panicle, with 26.11% increase in
      seed yield. For assessing the requirement of A. cerana to pollinate one hectare
      of cabbage, flower availability and the speed with which the pollen and nectar
      foragers process the flowers are taken into consideration. A forager is estimated
      to pollinate 4,780 flowers a day, but cabbage flower requires 9.09 visits of A.
      cerana for optimum seed set. Thus, a maximum of 4,999 bee foragers or 8.33
      colonies are needed to effectively pollinate 1 ha of cabbage. Though A. cerana is
      a good pollinator, our findings suggest that it is not an ideal pollinator of
      cabbage.

PMID- 28444379
TI  - Killing the killer: predation between protists and predatory bacteria.
AB  - Predation by microbes is one of the main drivers of bacterial mortality in the
      environment. In most ecosystems multiple micropredators compete at least
      partially for the same bacterial resource. Predatory interactions between these
      micropredators might lead to shifts within microbial communities. Integrating
      these interactions is therefore crucial for the understanding of ecosystem
      functioning. In this study, we investigated the predation between two groups of
      micropredators, i.e. phagotrophic protists and Bdellovibrio and like organisms
      (BALOs). BALOs are obligate predators of Gram-negative bacteria. We hypothesised
      that protists can prey upon BALOs despite the small size and high swimming speed
      of the latter, which makes them potentially hard to capture. Predation
      experiments including three protists, i.e. one filter feeder and two interception
      feeder, showed that BALOs are a relevant prey for these protists. The growth rate
      on BALOs differed for the respective protists. The filter feeding ciliate was
      growing equally well on the BALOs and on Escherichia coli, whereas the two
      flagellate species grew less well on the BALOs compared to E. coli. However,
      BALOs might not be a favourable food source in resource-rich environments as they
      are not enabling all protists to grow as much as on bacteria of bigger volume.

PMID- 28444380
TI  - Polymorphisms in the LAC12 gene explain lactose utilisation variability in
      Kluyveromyces marxianus strains.
AB  - Kluyveromyces marxianus is a safe yeast used in the food and biotechnology
      sectors. One of the important traits that sets it apart from the familiar yeasts,
      Saccharomyces cerevisiae, is its capacity to grow using lactose as a carbon
      source. Like in its close relative, Kluyveromyces lactis, this requires lactose
      transport via a permease and intracellular hydrolysis of the disaccharide. Given
      the importance of the trait, it was intriguing that most, but not all, strains of
      K. marxianus are reported to consume lactose efficiently. In this study,
      primarily through heterologous expression in S. cerevisiae and K. marxianus, it
      was established that a single gene, LAC12, is responsible for lactose uptake in
      K. marxianus. Strains that failed to transport lactose showed variation in 13
      amino acids in the Lac12p protein, rendering the protein non-functional for
      lactose transport. Genome analysis showed that the LAC12 gene is present in four
      copies in the subtelomeric regions of three different chromosomes but only the
      ancestral LAC12 gene encodes a functional lactose transporter. Other copies of
      LAC12 may be non-functional or have alternative substrates. The analysis raises
      some interesting questions regarding the evolution of sugar transporters in K.
      marxianus.

PMID- 28444381
TI  - Evidence for Very Recent Positive Selection in Mongolians.
AB  - Mongols, the founders of the largest continental empire in history, successfully
      adapted to the harsh environments of Inner Asia through nomadic pastoralism.
      Considerable interest exists in ascertaining whether genetic adaptation also
      contributed to the Mongols' success, and dissecting the genome diversity of
      present-day populations in Mongolia can help address this question. To this end,
      we determined the genotypes of nearly 2.4 million single nucleotide polymorphisms
      (SNPs) of 96 unrelated Mongolian individuals in Ulaanbaatar city, and performed
      genome-wide scans for population-specific positive selection. We discovered
      signatures of Mongolian-specific positive selection at the chromosomal region
      3p12.1, in which hits in genome-wide association studies were reported for
      medical and biological traits related to energy metabolism and reproduction. The
      top SNP, rs117799927, showed a distinctive geographic distribution: the frequency
      of the derived allele, rs117799927 G, was extremely low among worldwide
      populations (0.005) but exceptionally high in Mongolians (0.247). Approximate
      Bayesian computation-based age estimation showed that the rs117799927 G allele
      emerged or positive selection began to operate 50 generations before the present,
      near the age of the climate anomaly named Late Antique Little Ice Age.
      Furthermore, rs117799927 showed significant associations with multiple adiposity
      related traits in Mongolians and allelic difference in enhancer activity in cells
      of adipocyte lineage, suggesting that positive selection at 3p12.1 might be
      related to adaptation in the energy metabolism system. These findings provide
      novel evidence for a very recent positive-selection event in Homo sapiens and
      offer insights into the roles of genes in 3p12.1 in the adaptive evolution of our
      species.

PMID- 28444382
TI  - Xylem traits, leaf longevity and growth phenology predict growth and mortality
      response to defoliation in northern temperate forests.
AB  - Defoliation outbreaks are biological disturbances that alter tree growth and
      mortality in temperate forests. Trees respond to defoliation in many ways; some
      recover rapidly, while others decline gradually or die. Functional traits such as
      xylem anatomy, growth phenology or non-structural carbohydrate (NSC) storage
      could explain these responses, but idiosyncratic measures used by defoliation
      studies have frustrated efforts to generalize among species. Here, I test for
      functional differences with published growth and mortality data from 37 studies,
      including 24 tree species and 11 defoliators from North America and Eurasia. I
      synthesized data into standardized variables suitable for numerical models and
      used linear mixed-effects models to test the hypotheses that responses to
      defoliation vary among species and functional groups. Standardized data show that
      defoliation responses vary in shape and degree. Growth decreased linearly or
      curvilinearly, least in ring-porous Quercus and deciduous conifers (by 10-40% per
      100% defoliation), whereas growth of diffuse-porous hardwoods and evergreen
      conifers declined by 40-100%. Mortality increased exponentially with defoliation,
      most rapidly for evergreen conifers, then diffuse-porous, then ring-porous
      species and deciduous conifers (Larix). Goodness-of-fit for functional-group
      models was strong (R2c = 0.61-0.88), if lower than species-specific mixed-models
      (R2c = 0.77-0.93), providing useful alternatives when species data are lacking.
      These responses are consistent with functional differences in leaf longevity,
      wood growth phenology and NSC storage. When defoliator activity lags behind wood
      growth, either because xylem-growth precedes budburst (Quercus) or defoliator
      activity peaks later (sawflies on Larix), impacts on annual wood-growth will
      always be lower. Wood-growth phenology of diffuse-porous species and evergreen
      conifers coincides with defoliation and responds more drastically, and lower
      axial NSC storage makes them more vulnerable to mortality as stress accumulates.
      These functional differences in response apply in general to disturbances that
      cause spring defoliation and provide a framework that should be incorporated into
      forest growth and vegetation models.

PMID- 28444383
TI  - Optimizing drug-dose alerts using commercial software throughout an integrated
      health care system.
AB  - All default electronic health record and drug reference database vendor drug-dose
      alerting recommendations (single dose, daily dose, dose frequency, and dose
      duration) were silently turned on in inpatient, outpatient, and emergency
      department areas for pediatric-only and nonpediatric-only populations. Drug-dose
      alerts were evaluated during a 3-month period. Drug-dose alerts fired on 12% of
      orders (104 098/834 911). System-level and drug-specific strategies to decrease
      drug-dose alerts were analyzed. System-level strategies included: (1) turning off
      all minimum drug-dosing alerts, (2) turning off all incomplete information drug
      dosing alerts, (3) increasing the maximum single-dose drug-dose alert threshold
      to 125%, (4) increasing the daily dose maximum drug-dose alert threshold to 125%,
      and (5) increasing the dose frequency drug-dose alert threshold to more than 2
      doses per day above initial threshold. Drug-specific strategies included changing
      drug-specific maximum single and maximum daily drug-dose alerting parameters for
      the top 22 drug categories by alert frequency. System-level approaches decreased
      alerting to 5% (46 988/834 911) and drug-specific approaches decreased alerts to
      3% (25 455/834 911). Drug-dose alerts varied between care settings and patient
      populations.

PMID- 28444384
TI  - E-Science technologies in a workflow for personalized medicine using cancer
      screening as a case study.
AB  - Objective: We provide an e-Science perspective on the workflow from risk factor
      discovery and classification of disease to evaluation of personalized
      intervention programs. As case studies, we use personalized prostate and breast
      cancer screenings. Materials and Methods: We describe an e-Science initiative in
      Sweden, e-Science for Cancer Prevention and Control (eCPC), which supports
      biomarker discovery and offers decision support for personalized intervention
      strategies. The generic eCPC contribution is a workflow with 4 nodes applied
      iteratively, and the concept of e-Science signifies systematic use of tools from
      the mathematical, statistical, data, and computer sciences. Results: The eCPC
      workflow is illustrated through 2 case studies. For prostate cancer, an in-house
      personalized screening tool, the Stockholm-3 model (S3M), is presented as an
      alternative to prostate-specific antigen testing alone. S3M is evaluated in a
      trial setting and plans for rollout in the population are discussed. For breast
      cancer, new biomarkers based on breast density and molecular profiles are
      developed and the US multicenter Women Informed to Screen Depending on Measures
      (WISDOM) trial is referred to for evaluation. While current eCPC data management
      uses a traditional data warehouse model, we discuss eCPC-developed features of a
      coherent data integration platform. Discussion and Conclusion: E-Science tools
      are a key part of an evidence-based process for personalized medicine. This paper
      provides a structured workflow from data and models to evaluation of new
      personalized intervention strategies. The importance of multidisciplinary
      collaboration is emphasized. Importantly, the generic concepts of the suggested
      eCPC workflow are transferrable to other disease domains, although each disease
      will require tailored solutions.

PMID- 28444385
TI  - The effects of Bacillus coagulans-fermented and non-fermented Ginkgo biloba on
      abdominal fat deposition and meat quality of Peking duck.

PMID- 28444386
TI  - Coevolution with pollinating resin midges led to resin-filled nurseries in the
      androecia, gynoecia and tepals of Kadsura (Schisandraceae).
AB  - Background and Aims: Resin is a defence against herbivores and a floral reward in
      a few African and South American species whose bee pollinators collect it for
      nest construction. Here we describe a new role for floral resin from the Asian
      genus Kadsura (Schisandraceae). Kadsura tepals tightly cover a globe formed by
      carpels (in females) or near-fused stamens with fleshy connectives (in male
      flowers of most, but not all species). Methods: We carried out field observations
      at four sites in China and used pollinator behavioural assays, chemical analyses
      and time-calibrated insect and plant phylogenies to investigate the specificity
      of the interactions and their relationship to floral structure. Key Results:
      Nocturnal resin midges ( Resseliella , Cecidomyiidae) walk around on the flowers'
      sexual organs to oviposit, thereby transferring pollen and wounding tissues. The
      larvae then develop in resin-filled chambers. Male and female floral scents are
      dominated by alpha-pinene, while the resinous exudate is dominated by
      caryophyllene. As revealed by barcoding of multiple midge larvae per flower
      species, the mutualisms are species specific and appear to have evolved over the
      past 6-9 million years. Conclusions: Resin feeding, not pollen or ovule feeding,
      by midge larvae explains the abundant Kadsura exudates, highlighting the poorly
      known world of nocturnal flower-fly interactions.

PMID- 28444387
TI  - Meiotic Genes Are Enriched in Regions of Reduced Archaic Ancestry.
AB  - About 1-6% of the genetic ancestry of modern humans today originates from
      admixture with archaic humans. It has recently been shown that autosomal genomic
      regions with a reduced proportion of Neanderthal and Denisovan ancestries (NA and
      DA) are significantly enriched in genes that are more expressed in testis than in
      other tissues. To determine whether a cellular segregation pattern would exist,
      we combined maps of archaic introgression with a cross-analysis of three
      transcriptomic datasets deciphering the transcriptional landscape of human
      gonadal cell types. We reveal that the regions deficient in both NA and DA
      contain a significant enrichment of genes transcribed in meiotic germ cells. The
      interbreeding of anatomically modern humans with archaic humans may have
      introduced archaic-derived alleles that contributed to genetic incompatibilities
      affecting meiosis that were subsequently purged by natural selection.

PMID- 28444388
TI  - APOEepsilon4 Genotype and Hypertension Modify 8-year Cortical Thinning: Five
      Occasion Evidence from the Seattle Longitudinal Study.
AB  - We investigated individual differences in longitudinal trajectories of brain
      aging in cognitively normal healthy adults from the Seattle Longitudinal Study
      covering 8 years of longitudinal change (across 5 occasions) in cortical
      thickness in 249 midlife and older adults (52-95 years old). We aimed to
      understand true brain change; examine the influence of salient risk factors that
      modify an individual's rate of cortical thinning; and compare cross-sectional age
      related differences in cortical thickness to longitudinal within-person cortical
      thinning. We used Multivariate Multilevel Modeling to simultaneously model
      dependencies among 5 lobar composites (Frontal, Parietal, Temporal, Occipital,
      and Cingulate [CING]) and account for the longitudinal nature of the data.
      Results indicate (1) all 5 lobar composites significantly atrophied across 8
      years, showing nonlinear longitudinal rate of cortical thinning decelerated over
      time, (2) longitudinal thinning was significantly altered by hypertension and
      Apolipoprotein-E epsilon4 (APOEepsilon4), varying by location: Frontal and CING
      thinned more rapidly in APOEepsilon4 carriers. Notably, thinning of parietal and
      occipital cortex showed synergistic effect of combined risk factors, where
      individuals who were both APOEepsilon4 carriers and hypertensive had
      significantly greater 8-year thinning than those with either risk factor alone or
      neither risk factor, (3) longitudinal thinning was 3 times greater than cross
      sectional estimates of age-related differences in thickness in parietal and
      occipital cortices.

PMID- 28444389
TI  - SmithRNAs: Could Mitochondria "Bend" Nuclear Regulation?
AB  - Typically, animal mitochondria have very compact genomes, with few short
      intergenic regions, and no introns. Hence, it may seem that there is little space
      for unknown functions in mitochondrial DNA (mtDNA). However, mtDNA can also
      operate through RNA interference, as small non coding RNAs (sncRNAs) produced by
      mtDNA have already been proposed for humans. We sequenced sncRNA libraries from
      isolated mitochondria of Ruditapes philippinarum (Mollusca Bivalvia) gonads, a
      species with doubly uniparental inheritance of mitochondria, and identified
      several putative sncRNAs of mitochondrial origin. Some sncRNAs are transcribed by
      intergenic regions that form stable stem-hairpin structures, which makes them
      good miRNA-like candidates. We decided to name them small mitochondrial highly
      transcribed RNAs (smithRNAs). Many concurrent data support that we have recovered
      sncRNAs of mitochondrial origin that might be involved in gonad formation and
      able to affect nuclear gene expression. This possibility has been never suggested
      before. If mtDNA can affect nuclear gene expression through RNA interference,
      this opens a plethora of new possibilities for it to interact with the nucleus,
      and makes metazoan mtDNA a much more complex genome than previously thought.

PMID- 28444390
TI  - Characterization of Drug-Specific Signaling Between Primary Human Hepatocytes and
      Immune Cells.
AB  - It is now apparent that antigen-specific T-cells are activated in certain
      patients with drug-induced liver injury (DILI). Since cross-talk between
      hepatocytes and immune cells is likely to be critical in determining the outcome
      of drug exposure, the aim of this study was to profile the signals released by
      drug-treated hepatocytes and to characterize the impact of these molecules on
      dendritic cells. Human hepatocytes were exposed to 3 drugs (flucloxacillin,
      amoxicillin, and isoniazid) associated with DILI potentially mediated by the
      adaptive immune system as drug-specific T-cells have been isolated from DILI
      patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO). Hepatocyte
      toxicity, cytokine release and activation of oxidative stress pathways were
      measured. Supernatants were transferred to monocyte-derived dendritic cells and
      cell phenotype and function were assessed. High-mobility group box 1 protein
      (HMGB1) and lactate dehydrogenase release as well as adenosine triphosphate
      depletion occurred in a drug-, time-, and concentration-dependent manner with SMX
      NO and flucloxacillin, whereas isoniazid and amoxicillin were nontoxic.
      Furthermore, drug-induced activation of nuclear factor (erythroid-derived 2)-like
      2 marker genes was observed when hepatocytes were exposed to test drugs. The
      disulfide isoform of HMGB1 stimulated dendritic cell cytokine release and
      enhanced the priming of naive T-cells. Incubation of dendritic cells with
      supernatant from drug-treated hepatocytes resulted in 2 distinct cytokine
      profiles. SMX-NO/flucloxacillin stimulated secretion of TNF-alpha, IL-6, IL
      1alpha, and IL-1-beta. Isoniazid which did not induce significant hepatocyte
      toxicity, compared with SMX-NO and flucloxacillin, stimulated the release of a
      panel of cytokines including the above and IFN-gamma, IL-12, IL-17A, IP-10, and
      IL-10. Collectively, our study identifies drug-specific signaling pathways
      between hepatocytes and immune cells that could influence whether drug exposure
      will result in an immune response and tissue injury.

PMID- 28444391
TI  - Dual display: phage selection driven by co-engagement of two targets by two
      different antibody fragments.
AB  - Antibody phage display technology has supported the emergence of numerous
      therapeutic antibodies. The development of bispecific antibodies, a promising new
      frontier in antibody therapy, could be facilitated by new phage display
      approaches that enable pairs of antibodies to be co-selected based on co
      engagement of their respective targets. We describe such an approach, making use
      of two complementary leucine zipper domains that heterodimerize with high
      affinity. Phagemids encoding a first antibody fragment (scFv) fused to phage coat
      protein via the first leucine zipper are rescued in bacteria expressing a second
      scFv fused to the second leucine zipper as a soluble periplasmic protein, so that
      it is acquired by phage during assembly. Using a soluble scFv specific for a
      human CD3-derived peptide, we show that its acquisition by phage displaying an
      irrelevant antibody is sufficiently robust to drive selection of rare phage (1 in
      10(5)) over three rounds of panning. We then set up a model selection experiment
      using a cell line expressing the chemokine receptor CCR5 fused to the CD3 peptide
      together with a panel of phage clones capable displaying either an anti-CCR5 scFv
      or an irrelevant antibody, with or without the capacity to acquire the soluble
      anti-CD3 scFv. In this experiment we showed that rare phage (1 in 10(5)) capable
      of displaying the two different scFvs can be specifically enriched over four
      rounds of panning. This approach has the potential to be applied to the
      identification of pairs of ligands capable of co-engaging two different user
      defined targets, which would facilitate the discovery of novel bispecific
      antibodies.

PMID- 28444392
TI  - The EMBO biocatalysis conference "The biochemistry and chemistry of biocatalysis:
      from understanding to design".

PMID- 28444393
TI  - Response to the 'Comment on the editorial by Turner et al. on Assessment of
      cardiovascular risk of new drugs for the treatment of diabetes mellitus: risk
      assessment vs. risk aversion by Zannad et al.'

PMID- 28444394
TI  - Tissue-Specific Dissociation of Diurnal Transcriptome Rhythms During Sleep
      Restriction in Mice.
AB  - Study objectives: Shortened or mistimed sleep affects metabolic homeostasis,
      which may in part be mediated by dysregulation of endogenous circadian clocks. In
      this study, we assessed the contribution of sleep disruption to metabolic
      dysregulation by analysing diurnal transcriptome regulation in metabolic tissues
      of mice subjected to a sleep restriction (SR) paradigm. Methods: Male mice were
      subjected to 2 * 5 days of SR with enforced waking during the first 6 hours of
      the light phase. SR and control mice were sacrificed at different time points of
      the day and RNA preparations from the mediobasal hypothalamus (MBH), liver, and
      epididymal white adipose tissue (eWAT) were subjected to whole-genome microarray
      hybridization. Transcriptional rhythms were associated with changes in behavioral
      and physiological parameters such as sleep, body temperature, and food intake.
      Rhythm detection was performed with CircWave and transcription profiles were
      compared by 2-way analysis of variance and t-tests with Benjamini-Hochberg
      corrections. Results: Clock gene rhythms were blunted in all tissues, while
      transcriptome regulation was associated with either clock gene expression, sleep
      patterns, or food intake in a tissue-specific manner. Clock gene expression was
      associated with apoptosis pathways in the MBH and with tumor necrosis factor
      alpha signalling in liver. Food intake-associated genes included cilium movement
      genes in the MBH and lipid metabolism-associated transcripts in liver.
      Conclusions: In mice, repeated SR profoundly alters behavioral and molecular
      diurnal rhythms, disrupting essential signalling pathways in MBH, liver, and
      eWAT, which may underlie the metabolic and cognitive disturbances observed in
      sleep-restricted humans such as shift workers.

PMID- 28444395
TI  - Effects of N-acetyl-L-cysteine on the membrane vesicle release and growth of
      respiratory pathogens.
AB  - Bacterial infections contribute to the disease progression of chronic obstructive
      pulmonary disease by stimulating mucus production in the airways. This increased
      mucus production and other symptoms are often alleviated when patients are
      treated with mucolytics such as N-acetyl-L-cysteine (NAC). Moreover, NAC has been
      suggested to inhibit bacterial growth. Bacteria can release membrane vesicles
      (MVs) in response to stress, and recent studies report a role for these
      proinflammatory MVs in the pathogenesis of airways disease. Yet, until now it is
      not clear whether NAC also affects the release of these MVs. This study set out
      to determine whether NAC, at concentrations reached during high-dose
      nebulization, affects bacterial growth and MV release of the respiratory
      pathogens non-typeable Haemophilus influenzae (NTHi), Moraxella catarrhalis
      (Mrc), Streptococcus pneumoniae (Spn) and Pseudomonas aeruginosa (Psa). We
      observed that NAC exerted a strong bacteriostatic effect, but also induced the
      release of proinflammatory MVs by NTHi, Mrc and Psa, but not by Spn.
      Interestingly, NAC also markedly blunted the release of TNF-alpha by naive
      macrophages in response to MVs. This suggests that the application of NAC by
      nebulization at a high dosage may be beneficial for patients with airway
      conditions associated with bacterial infections.

PMID- 28444396
TI  - Circadian Impairment of Distal Skin Temperature Rhythm in Patients With Sleep
      Disordered Breathing: The Effect of CPAP.
AB  - Study objectives: Our aim was to evaluate the circadian rhythm of distal skin
      temperature (DST) in sleep-disordered breathing (SDB), its relation to excessive
      daytime sleepiness and the effect of continuous positive airway pressure (CPAP)
      on DST. Methods: Eighty SDB patients (53.1 +/- 1.2 years old, 27.6% women) and 67
      healthy participants (52.3 +/- 1.6 years old, 26.9% women) wore a temperature
      data logger for 1 week. On the last day of that week, SDB patients underwent a
      polysomnography followed by a Maintenance of Wakefulness Test (MWT), Multiple
      Sleep Latency Test, and Sustained Attention to Response Task protocol to
      objectively quantify daytime sleepiness. A subset of 21 moderate to severe SDB
      patients were treated with CPAP during at least 3 months and revaluated with the
      same procedure. A nonparametric analysis was performed to characterize DST to
      assess differences between groups and associations among DST, polysomnography,
      and daytime sleepiness measures. Results: SDB patients showed an unstable,
      fragmented, flattened, phase-advanced, and less robust DST rhythm as compared to
      healthy participants. The more severe the SDB, the worse the DST pattern was, as
      indicated by the correlation coefficient. Sleepiness, according to MWT sleep
      latencies, was also associated with the higher fragmentation, lower amplitude,
      and less robustness of the DST rhythm. Treatment with CPAP improved DST pattern
      regularity and robustness. Conclusion: DST is altered in SDB, exhibiting a direct
      relationship to the severity of this condition, and improves with CPAP treatment.
      DST independently correlates with sleepiness, thus, its measurement may
      contribute to the understanding of the pathophysiology of sleepiness in these
      patients.

PMID- 28444397
TI  - Advancing the efficiency and efficacy of patient reported outcomes with
      multivariate computer adaptive testing.
AB  - Objective: The Patient Reported Outcomes Measurement Information System (PROMIS)
      initiative developed an array of patient reported outcome (PRO) measures. To
      reduce the number of questions administered, PROMIS utilizes unidimensional item
      response theory and unidimensional computer adaptive testing (UCAT), which means
      a separate set of questions is administered for each measured trait.
      Multidimensional item response theory (MIRT) and multidimensional computer
      adaptive testing (MCAT) simultaneously assess correlated traits. The objective
      was to investigate the extent to which MCAT reduces patient burden relative to
      UCAT in the case of PROs. Methods: One MIRT and 3 unidimensional item response
      theory models were developed using the related traits anxiety, depression, and
      anger. Using these models, MCAT and UCAT performance was compared with simulated
      individuals. Results: Surprisingly, the root mean squared error for both methods
      increased with the number of items. These results were driven by large errors for
      individuals with low trait levels. A second analysis focused on individuals
      aligned with item content. For these individuals, both MCAT and UCAT accuracies
      improved with additional items. Furthermore, MCAT reduced the test length by 50%.
      Discussion: For the PROMIS Emotional Distress banks, neither UCAT nor MCAT
      provided accurate estimates for individuals at low trait levels. Because the
      items in these banks were designed to detect clinical levels of distress, there
      is little information for individuals with low trait values. However, trait
      estimates for individuals targeted by the banks were accurate and MCAT asked
      substantially fewer questions. Conclusion: By reducing the number of items
      administered, MCAT can allow clinicians and researchers to assess a wider range
      of PROs with less patient burden.

PMID- 28444398
TI  - Plasma Transfusion Demystified: A Review of the Key Factors Influencing the
      Response to Plasma Transfusion.
AB  - Many studies have suggested that inappropriate plasma usage is common. An
      important factor contributing to futile plasma administration in most patients is
      the nonlinear relationship between coagulation-factor levels and the volume of
      plasma transfused. In this review, a validated mathematical model and data from
      the literature will be used to illuminate 3 key properties of plasma transfusion.
      Those properties are as follows: the effect of plasma transfusion on
      international normalized ratio (INR) is transient; for the same volume of
      transfused plasma, a greater reduction in INR is observed at higher initial INRs;
      and the effect of plasma transfusion on INR correction (ie, the difference
      between initial and final INRs) diminishes as more plasma is transfused. Frequent
      misunderstanding of these properties may contribute to inappropriate plasma
      usage. Therefore, this review will assist physicians in navigating these common
      pitfalls. Stronger understanding of these principles may result in a reduction of
      inappropriate plasma transfusions, thus potentially enhancing patient safety and
      reducing healthcare costs.

PMID- 28444399
TI  - Development of a multipurpose scaffold for the display of peptide loops.
AB  - Protein-protein interactions (PPIs) determine a wide range of biological
      processes and analysis of these dynamic networks is increasingly becoming a
      mandatory tool for studying protein function. Using the globular ATPase domain of
      recombinase RadA as a scaffold, we have developed a peptide display system (RAD
      display), which allows for the presentation of target peptides, protein domains
      or full-length proteins and their rapid recombinant production in bacteria. The
      design of the RAD display system includes differently tagged versions of the
      scaffold, which allows for flexibility in the protein purification method, and
      chemical coupling for small molecule labeling or surface immobilization. When
      combined with the significant thermal stability of the RadA protein, these
      features create a versatile multipurpose scaffold system. Using various
      orthogonal biophysical techniques, we show that peptides displayed on the
      scaffold bind to their natural targets in a fashion similar to linear parent
      peptides. We use the examples of CK2beta/CK2alpha kinase and TPX2/Aurora A kinase
      protein complexes to demonstrate that the peptide displayed by the RAD scaffold
      can be used in PPI studies with the same binding efficacy but at lower costs
      compared with their linear synthetic counterparts.

PMID- 28444400
TI  - Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH
      Stimulation in Healthy Men.
AB  - Study Objectives: Severe sleep restriction results in elevated evening cortisol
      levels. We examined whether this relative hypercortisolism is associated with
      alterations in the pituitary-adrenocortical response to evening corticotropin
      releasing hormone (CRH) stimulation. Methods: Eleven subjects participated in 2
      sessions (2 nights of 10 hours vs. 4 hours in bed) in randomized order. Sleep was
      polygraphically recorded. After the second night of each session, blood was
      sampled at 20-minute intervals from 09:00 to 24:00 for adrenocorticotropic
      hormone (ACTH) and cortisol measurements, and perceived stress was assessed
      hourly. Ovine CRH was injected at 18:00 (1 ug/kg body weight). Results: Prior to
      CRH injection, baseline ACTH, but not cortisol, levels were elevated after sleep
      restriction. Relative to the well-rested condition, sleep restriction resulted in
      a 27% decrease in overall ACTH response to CRH (estimated by the incremental area
      under the curve from 18:00 to 24:00; p = .002) while the cortisol response was
      decreased by 21% (p = .083). Further, the magnitude of these decreases was
      correlated with the individual amount of sleep loss (ACTH: rSp = -0.65, p = .032;
      cortisol: rSp = -0.71, p = .015). The acute post-CRH increment of cortisol was
      reduced (p = .002) without changes in ACTH reactivity, suggesting decreased
      adrenal sensitivity. The rate of decline from peak post-injection levels was
      reduced for cortisol (p = .032), but not for ACTH. Scores of perceived stress
      were unaffected by CRH injection and were low and similar under both sleep
      conditions. Conclusions: Sleep restriction is associated with a reduction of the
      overall ACTH and cortisol responses to evening CRH stimulation, and a reduced
      reactivity and slower recovery of the cortisol response.

PMID- 28444405
TI  - Focus on acute care surgery.

PMID- 28444406
TI  - [King's Parkinson's disease pain scale : Intercultural adaptation in the German
      language].
AB  - BACKGROUND: Pain is a frequent symptom of idiopathic Parkinson's disease and has
      a substantial impact on quality of life. The King's Parkinson's disease pain
      scale (KPPS) has become internationally established and is an English-language,
      standardized, reliable and valid scale for evaluation of pain in idiopathic
      Parkinson's disease. This article presents a validated version in German. METHOD:
      The German translation was adapted interculturally and developed using an
      internationally recognized procedure in consultation with the authors of the
      original publication. The primary text was first translated by two bilingual
      neuroscientists independently of one another. Thereafter, the two versions were
      collated to generate a consensus version, which was accepted by the translators
      and preliminarily trialled with 10 patients. Hereafter, the German version was re
      translated back into English by two other neurologists, again independently of
      one another, and a final consensus was agreed on using these versions. This
      English version was then compared with the original text by all of the
      translators, a process which entailed as many linguistic modifications to the
      German version as the translators considered necessary to generate a
      linguistically acceptable German version that was as similar as possible to the
      original English version. After this test text had been subsequently approved by
      the authors, the German text was applied to 50 patients in two hospitals, and
      reviewed as to its practicability and comprehensibility. RESULTS: This work led
      to the successful creation of an inter-culturally adapted and linguistically
      validated German version of the KPPS. DISCUSSION: The German version presented
      here is a useful scare for recording and quantifying pain in empirical studies,
      as well as in clinical practice.

PMID- 28444407
TI  - [Aseptic loosening of total ankle replacement and conversion to ankle
      arthrodesis].
AB  - OBJECTIVE: To remove loosened prosthesis components, to perform augmentation, to
      address osseous defects, to perform neutrally aligned ankle arthrodesis, and to
      achieve postoperative pain relief. INDICATIONS: Symptomatic, aseptic loosening of
      total ankle replacement (TAR) with/without substantial bone defect of the tibial
      and/or talar bone stock. CONTRAINDICATIONS: General surgical or anesthesiological
      risks, periprosthetic infection, local or systemic infection, nonmanageable soft
      tissue problems. SURGICAL TECHNIQUE: Removal of both prosthesis components using
      the previous incision (mostly using anterior ankle approach). Careful debridement
      of bone stock at the tibial and talar side. Osseous augmentation of defects using
      autologous or homologous cancellous bone, if needed, using structural allografts.
      POSTOPERATIVE MANAGEMENT: A soft wound dressing is used. Thromboprophylaxis is
      recommended. Patient mobilization starts on postoperative day 1 with 15 kg
      partial weight bearing using a stabilizing walking boot or cast for 6-8 weeks.
      Following clinical and radiographic follow-up at 6 weeks, full weight bearing is
      initiated gradually after progressive osseous healing has been confirmed.
      RESULTS: Between January 2007 and December 2012, ankle arthrodesis was performed
      in 9 patients with failed TAR (6 men and 3 women, mean age 56.4 +/- 7.0 years,
      range 47.8-66.0 years). The mean time between the initial TAR and revision
      surgery was 4.5 +/- 2.4 years (range 1.2-7.9 years). In one patient irrigation
      and debridement was performed due to superficial wound infection. Another patient
      had a delayed osseous healing 11 months after the revision surgery.

PMID- 28444408
TI  - Prolapse assessment supine and standing: do we need different cutoffs for
      "significant prolapse"?
AB  - INTRODUCTION AND HYPOTHESIS: Translabial ultrasound (TLUS) has shown good
      correlations between clinical examination and imaging findings in the supine
      position, and limits of normality have been described. This is not the case for
      imaging in the standing position. This study was designed to test the hypothesis
      that different cutoff values are required for imaging in the standing position.
      METHODS: This was a retrospective study carried out in a tertiary
      urogynecological unit in women presenting with symptoms of lower urinary tract
      and pelvic floor dysfunction between August 2013 and December 2015. All women
      underwent a standardized interview, 4D TLUS and a POP-Q assessment. Organ descent
      on ultrasound was measured relative to the postero-inferior margin of the
      symphysis pubis (SP) on maximal Valsalva in the supine and standing positions.
      Receiver operator characteristic (ROC) statistics were used to determine optimal
      cutoffs for "normal" pelvic organ support. RESULTS: We assessed 243 data sets.
      Mean patient age was 57 years. Prolapse symptoms were reported by 59.2%, and POP
      of stage >= 2 was found in 82.3%. On analysing imaging data sets obtained in the
      standing position, we obtained similar cutoff values to those established
      previously for supine imaging, using ROC statistics. The levator hiatus distended
      significantly more on Valsalva in the standing position compared with supine, and
      on ROC analysis we identified a new optimal cutoff of 29 cm2. CONCLUSIONS:
      Established cutoffs for supine imaging of organ descent are suitable for imaging
      in the standing position. Hiatal distensibility may require a higher cutoff of 29
      cm2.

PMID- 28444410
TI  - [Apnea test for assessment of brain death under extracorporeal life support].
AB  - BACKGROUND: The fourth edition of the German guideline for the assessment of
      brain death, published in 2015 by the German Medical Council (Bundesarztekammer),
      emphasizes the importance of an apnea test. It is also now required under all
      circumstances of extracorporeal life support. OBJECTIVES: This article is an
      instruction for the guideline-conforming performance of an apnea test in general
      and also in cases of extracorporeal life support in different configurations.
      MATERIALS AND METHODS: A literature review was performed. CONCLUSIONS: The apnea
      test is an essential part of the bedside examination for the clinical diagnosis
      of brain death. It is required for all kinds of extracorporeal life support and
      can be easily performed without endangering the patient. More accurate
      recommendations for its performance should be considered for the next version of
      the German guideline for brain death assessment.

PMID- 28444409
TI  - Diagnostic work-up and specific causes of acute kidney injury.
AB  - Acute kidney injury (AKI) is common in critically ill patients and associated
      with grim short- and long-term outcome. Although in the vast majority of cases
      AKI is multifactorial, with sepsis, shock and nephrotoxicity accounting for most
      episodes, specific causes of AKI are not uncommon. Despite remaining
      uncertainties regarding their prevalence in the ICU, prompt recognition of
      specific aetiologies of AKI is likely to ensure timely management, limit
      worsening of renal dysfunction, and ultimately limit renal and systemic
      consequences of AKI. The ability to recognize conditions that may be associated
      with specific aetiologies and the appropriate use of clinical imaging, biological
      and immunological tests, along with optimal assessment of the need for renal
      biopsies, should be part of routine ICU care. In this review, we summarize
      uncertainties, current knowledge and recent advances regarding specific types of
      AKI. We describe the most common specific causes as well as rare aetiologies
      requiring urgent management, and outline available tools that may be used during
      the diagnostic work-up along with their limitations.

PMID- 28444411
TI  - [Acute liver failure].
AB  - Acute liver failure (ALF) is a rare, but life-threatening disease that is
      characterized by the acute onset of jaundice, coagulopathy, and hepatic
      encephalopathy (HE) in patients without pre-existing liver disease. Main causes
      in Germany are drug toxicity, acetaminophen overdose, and viral hepatitis (A, B,
      E). For the initial assessment of patients with ALF and the diagnostic algorithm,
      the early detection of HE, exclusion of liver cirrhosis, immediate diagnosis of
      the underlying etiology, and evaluation for the necessity of liver
      transplantation (LT) are critical. Intensive care therapeutic measures aim at
      preventing or treating complications of ALF. Potentially, plasmapheresis (full
      plasma exchange) offers a survival benefit for ALF patients who do not undergo
      LT. The King's College criteria and the Clichy criteria are used as prognostic
      tools for the indication for LT.

PMID- 28444412
TI  - Biochemical and genetic analyses of N metabolism in maize testcross seedlings: 1.
      Leaves.
AB  - KEY MESSAGE: Aside from the identification of 32 QTL for N metabolism in the
      seedling leaves of a maize testcross population, alanine aminotransferase was
      found to be a central enzyme in N assimilation. Excessive application of nitrogen
      (N) fertilizer to grow commercial crops like maize is a cause of concern because
      of the runoff of excess N into streams and rivers. Breeding maize with improved N
      use efficiency (NUE) would reduce environmental pollution as well as input costs
      for the farmers. An understanding of the genetics underlying N metabolism is key
      to breeding for NUE. From a set of 176 testcrosses derived from the maize
      IBMsyn10 population grown in hydroponics, we analyzed the youngest fully expanded
      leaf at four-leaf stage for enzymes and metabolites related to N metabolism.
      Three enzymes, along with one metabolite explained 24% of the variation in shoot
      dry mass. Alanine aminotransferase (AlaAT) stood out as the key enzyme in
      maintaining the cellular level of glutamate as it alone explained 58% of the
      variation in this amino acid. Linkage mapping revealed 32 quantitative trait loci
      (QTL), all trans to the genomic positions of the structural genes for various
      enzymes of N assimilation. The QTL models for different traits accounted for 7
      31% of the genetic variance, whereas epistasis was generally not significant.
      Five coding regions underlying 1-LOD QTL confidence intervals were identified for
      further validation studies. Our results provide evidence for the key role of
      AlaAT in N assimilation likely through homeostatic control of glutamate levels in
      the leaf cells. The two QTL identified for this enzyme would help to select
      desirable recombinants for improved N assimilation.

PMID- 28444414
TI  - [General diagnostic work-up for benign tumors of the musculoskeletal system].
AB  - INTRODUCTION: Benign bone tumors are heterogeneous and have different biological
      behaviors. Treatment requires knowledge of the principle diagnosis and clinical
      behavior to avoid, on the one hand, overtreatment and, on the other hand,
      incorrect diagnosis of a potentially malignant tumor. METHODS: Bone tumors of
      stage I (according to Enneking) should be observed clinically and radiologically.
      For stage II and stage III lesions, a biopsy should be performed, based on the
      corresponding oncological guidelines. RESULTS AND CONCLUSION: Soft tissue tumors
      have a different radiological behavior (especially in magnetic resonance images):
      while a lack of sharp cortical margins in bone tumors indicates an aggressive
      behavior, sharp margins in soft tissue tumors should not be misinterpreted as
      benign tumors. Subfascial soft tissue tumors, tumors larger than 2 cm, growing
      tumors, and persisting tumors after trauma require biopsy.

PMID- 28444413
TI  - Cerebral dopamine neurotrophic factor protects H9c2 cardiomyocytes from
      apoptosis.
AB  - BACKGROUND: Cerebral dopamine neurotrophic factor (CDNF) has been studied in
      animal models of Parkinson's disease, where it was shown to repair and protect
      dopamine neurons. Alongside its neurotrophic activity, it can also localize in
      the endoplasmic reticulum (ER) acting as an ER stress response (ERSR) protein to
      maintain ER homeostasis. Since ER stress plays a major role in the development
      and progression of cardiovascular diseases, we investigated the role of CDNF in
      cardiomyocytes during ER stress. MATERIAL AND METHODS: Initially, the expression
      of CDNF was tested by treating H9c2 cells with various concentrations of
      tunicamycin (TM) and performing reverse-transcriptase polymerase chain reaction
      and Western blotting. To evaluate the overexpression of CDNF in cardiomyocytes,
      H9c2 cells were transfected with pcDNA-CDNF and analyzed by Western blotting and
      indirect immunofluorescence microscopy. The effects of CDNF on cardiomyocytes
      during ER stress were analyzed with CCK-8 method and TUNEL staining using cells
      transfected with pcDNA-CDNF or pcDNA3.1. The percentage of TUNEL-positive cells
      was quantified as the apoptotic level. RESULTS: Our results showed that CDNF
      protein expression can be induced by activation of ER stress in cultured
      cardiomyocytes. Moreover, overexpression of CDNF improved cell viability and
      protected cardiomyocytes from apoptosis induced by ER stress. CONCLUSION: The
      findings presented here contribute toward identifying the physiological functions
      of CDNF in cardiovascular diseases.

PMID- 28444415
TI  - [Conventional radiological diagnosis of benign none neoplasms].
AB  - BACKGROUND: Benign bone tumors are of special clinical importance because they
      might be confused with malignant bone tumors. OBJECTIVES: The aim of this article
      it to present the characteristics of benign bone tumors. The focus is orientated
      towards conventional x-ray as the essential pillar for primary diagnosis.
      Consequently, the description of signal intensities of benign bone tumors in
      magnetic resonance images or less helpful clues like male-female ratios are
      deliberately omitted. RESULTS: The classification of bone tumors introduced by
      Lodwick allows the identification of benign growth patterns. Growth patterns will
      not help, for example, in case of dedifferentiation of benign chondroid tumors
      towards chondrosarcomas. Therefore, each diagnosis has to incorporate the
      patient's clinical scenario. Furthermore, benign bone tumors might also cause
      aggressive growth patterns. Tumors classified as Lodwick Ic or higher should not
      be automatically regarded as malignant. Naturally, further clarification is
      mandatory for these tumors. CONCLUSIONS: Differentiation between definitely
      benign bone tumors and those which need further work up is a critical diagnostic
      step. In the majority of cases, this is possible based on the appearance in
      conventional x-ray images. In case of possibly malignant lesions, both the
      patient's symptoms and the x-ray morphology have to be considered by orthopedic
      surgeons, pathologists, and radiologists to determine the optimal diagnostic
      strategy.

PMID- 28444417
TI  - Identification of proteins differentially expressed by Chlamydia trachomatis
      treated with chlamydiaphage capsid protein VP1 during intracellular growth.
AB  - Chlamydia trachomatis infection is one of the most prevalent sexually transmitted
      diseases. Our research pertains to the inhibitory effect and molecular mechanism
      of the chlamydiaphage capsid protein VP1 on the growth of Chlamydia trachomatis.
      In this research, the capsid protein VP1 of the guinea-pig conjunctivitis
      chlamydiaphage phiCPG1 was expressed, purified and identified, and then, it was
      applied to the cultivation of different serovars of Chlamydia trachomatis and
      Chlamydia psittaci. The inhibitory effect was observed in each serovar of
      Chlamydia trachomatis (D, E, F, G, H, I, K, and L2) and Chlamydia psittaci
      inoculated with VP1 protein. The inhibition affection of VP1 on the growth of
      Chlamydia trachomatis was caused by the changes of expressions of some related
      proteins including 36 proteins up-regulated and 81 proteins down-regulated in the
      development cycle of Ct through the label-free test, and the transcription levels
      of these proteins, including Hc1, pmpD, and MOMP, were confirmed by RT-PCR. It
      provides information that is essential for understanding the mechanism of
      chlamydiaphage capsid protein VP1 on chlamydia and a new direction for further
      clinical treatment of chlamydial infection.

PMID- 28444416
TI  - Control of DNA integrity in skeletal muscle under physiological and pathological
      conditions.
AB  - Skeletal muscle is a highly oxygen-consuming tissue that ensures body support and
      movement, as well as nutrient and temperature regulation. DNA damage induced by
      reactive oxygen species is present in muscles and tends to accumulate with age.
      Here, we present a summary of data obtained on DNA damage and its implication in
      muscle homeostasis, myogenic differentiation and neuromuscular disorders.
      Controlled and transient DNA damage appears to be essential for muscular
      homeostasis and differentiation while uncontrolled and chronic DNA damage
      negatively affects muscle health.

PMID- 28444418
TI  - Role of Flagella in the Pathogenesis of Helicobacter pylori.
AB  - This review aimed to investigate the role of Helicobacter pylori flagella on the
      pathogenicity of this bacterium in humans. Helicobacter pylori is a flagellated
      pathogen that colonizes the human gastroduodenal mucosa and produces
      inflammation, and is responsible for gastrointestinal disease. Its pathogenesis
      is attributed to colonization and virulence factors. The primary function of H.
      pylori flagella is to provide motility. We believe that H. pylori flagella play
      an important role in the colonization of the gastrointestinal mucosa. Therefore,
      we reviewed previous studies on flagellar morphology and motility in order to
      explore the relationship between H. pylori flagella and pathogenicity. Further
      investigation is required to confirm the association between flagella and
      pathogenicity in H. pylori.

PMID- 28444419
TI  - The Role of Localized Acidity Generation in Microbially Influenced Corrosion.
AB  - Microbially influenced corrosion is of great industrial concern. Microbial
      coupling of metal oxidation to sulfate-, nitrate-, nitrite-, or CO2-reduction is
      proton-mediated, and some sulfate-reducing prokaryotes are capable of regulating
      extracellular pH. The analysis of the corrosive processes catalyzed by nitrate
      reducing bacteria and methanogenic archaea indicates that these microorganisms
      may be capable of regulating extracellular pH as well. It is proposed that
      nutrient limitation at metal-biofilm interfaces may induce activation of
      enzymatic proton-producing/proton-secreting functions in respiratory and
      methanogenic microorganisms to make them capable of using Fe0 as the electron
      donor. This can be further verified through experiments involving measurements of
      ion and gas concentrations at metal-biofilm interfaces, microscopy, and
      transcriptomics analyses.

PMID- 28444420
TI  - Periportal lymphatic system on post-hepatobiliary phase Gd-EOB-DTPA-enhanced MR
      imaging in normal subjects and patients with chronic hepatitis C.
AB  - PURPOSE: We sought to evaluate visualization of periportal lymphatics and lymph
      nodes (lymphatic system) on Gd-EOB-DTPA-enhanced magnetic resonance (MR) images
      using a fat-suppressed T2-weighted sequence with 3-dimensional (3D) volume
      isotropic turbo spin echo acquisition (VISTA) at 3.0 T in normal subjects and
      patients with chronic hepatitis C. METHODS: MR imaging was performed in 254
      subjects between June 2013 and May 2016. After applying inclusion and exclusion
      criteria, the final population was 31 normal subjects and 34 patients with
      chronic hepatitis C. Images were acquired after the hepatobiliary phase following
      intravenous administration of Gd-EOB-DTPA, which causes signal loss in the bile
      ducts, to facilitate the visualization of the periportal lymphatic system. Two
      radiologists assessed the visualization of the periportal lymphatic system in 31
      normal subjects. The axial dimensions of the main periportal lymphatic system in
      normal subjects were measured and compared with those of 34 patients with chronic
      hepatitis C using the Mann-Whitney U-test, and their correlation with a hepatic
      fibrosis marker, the Fibrosis-4 (FIB-4), was assessed using Spearman's rank
      correlation test. RESULTS: The periportal lymphatic system was detected as high
      signal intensity areas surrounding the portal vein up to the third branches by
      each reader in all normal subjects. The axial dimensions of the main periportal
      lymphatic system in patients with chronic hepatitis C were significantly larger
      than those in normal subjects (p < 0.0001), and showed a significantly positive
      correlation with the FIB-4 score (rho = 0.73, p < 0.001). CONCLUSIONS: Fat
      suppressed T2-weighted MR imaging with 3D-VISTA acquired after the hepatobiliary
      phase on Gd-EOB-DTPA-enhanced imaging may be a useful noninvasive method for
      evaluating the periportal lymphatic system and the degree of hepatic fibrosis.

PMID- 28444421
TI  - Metal Levels in Shorebird Feathers and Blood During Migration Through Delaware
      Bay.
AB  - We investigated levels of arsenic mercury, lead, cadmium, and chromium in Red
      Knot (Calidris canutus), Semipalmated Sandpipers (Calidris pusilla), and
      Sanderling (Calidris alba) migrating through Delaware Bay, New Jersey to
      determine if contaminant levels are likely to be causing negative effects on the
      populations of these shorebirds, to compare among species, and to explore
      differences among individuals collected early and late during their migration
      stopover. We analyzed blood and feathers, both nonlethal ways of exploring
      contaminants in birds. Blood contaminant analysis provides a direct measure of
      recent dietary exposure, whereas feathers reflect body burden at the time of
      feather molt. We found some differences among species and between early and late
      samples. Levels of Hg and Pb were higher in Sanderling blood collected early
      (36.52 +/- 8.45 and 145.00 +/- 12.56 ng/g ww respectively) compared with later
      (16.21 +/- 6.03 and 33.60 +/- 4.05 ng/g ww respectively) during the migration
      stopover. Blood Pb levels of Sanderling in the early period were higher than
      those of the other two species (75.38 +/- 15.52 ng/g ww in Red Knot and 42.39 +/-
      8.42 ng/g ww in Semipalmated Sandpipers). Semipalmated Sandpipers had lower blood
      As levels than the other two species (254.33 +/- 40.15 and 512.00 +/- 66.79 ng/g
      ww early and late respectively) but higher feather levels (914.01 +/- 167.29 and
      770.00 +/- 116.21 ng/g dw early and late respectively), and their blood As was
      higher in the later sampling period compared with the early sampling period.
      Arsenic levels in shorebird tissues were relatively high and may reflect levels
      in horseshoe crab eggs, their primary diet item in Delaware Bay. In Red Knot,
      blood Cr levels were elevated in the later samples (572.17 +/- 62.82 ng/g ww)
      compared to the early samples (382.81 +/- 95.35 ng/g ww) and to the other
      species. The mean values of the metals analyzed were mostly below effect levels
      the level that has a measurable negative impact-although relatively high As
      levels in Semipalmated Sandpiper feathers and some high levels of Pb need to be
      further explored.

PMID- 28444422
TI  - Continuity vs. the Crowd-Tradeoffs Between Continuous and Intermittent Citizen
      Hydrology Streamflow Observations.
AB  - Hydrologic data has traditionally been collected with permanent installations of
      sophisticated and accurate but expensive monitoring equipment at limited numbers
      of sites. Consequently, observation frequency and costs are high, but spatial
      coverage of the data is limited. Citizen Hydrology can possibly overcome these
      challenges by leveraging easily scaled mobile technology and local residents to
      collect hydrologic data at many sites. However, understanding of how decreased
      observational frequency impacts the accuracy of key streamflow statistics such as
      minimum flow, maximum flow, and runoff is limited. To evaluate this impact, we
      randomly selected 50 active United States Geological Survey streamflow gauges in
      California. We used 7 years of historical 15-min flow data from 2008 to 2014 to
      develop minimum flow, maximum flow, and runoff values for each gauge. To mimic
      lower frequency Citizen Hydrology observations, we developed a bootstrap
      randomized subsampling with replacement procedure. We calculated the same
      statistics, and their respective distributions, from 50 subsample iterations with
      four different subsampling frequencies ranging from daily to monthly. Minimum
      flows were estimated within 10% for half of the subsample iterations at 39
      (daily) and 23 (monthly) of the 50 sites. However, maximum flows were estimated
      within 10% at only 7 (daily) and 0 (monthly) sites. Runoff volumes were estimated
      within 10% for half of the iterations at 44 (daily) and 12 (monthly) sites.
      Watershed flashiness most strongly impacted accuracy of minimum flow, maximum
      flow, and runoff estimates from subsampled data. Depending on the questions being
      asked, lower frequency Citizen Hydrology observations can provide useful
      hydrologic information.

PMID- 28444423
TI  - Canal of Nuck hernia: a multimodality imaging review.
AB  - Canal of Nuck abnormalities are a rare but important cause of morbidity in girls,
      most often those younger than 5 years of age. The canal of Nuck, which is the
      female equivalent of the male processus vaginalis, is a protrusion of parietal
      peritoneum that extends through the inguinal canal and terminates in the labia
      majora. The canal typically obliterates early in life, but in some cases the
      canal can partially or completely fail to close, potentially resulting in a
      hydrocele or hernia of pelvic contents. Recognition of this entity is especially
      important in cases of ovarian hernia due to the risk of incarceration and
      torsion. We aim to increase awareness of this condition by reviewing the
      embryology, anatomy and diagnosis of canal of Nuck disorders with imaging
      findings on US, CT and MRI using several cases from a single institution.

PMID- 28444424
TI  - The experience of immune checkpoint inhibitors in Chinese patients with
      metastatic melanoma: a retrospective case series.
AB  - Melanomas in Chinese patients show relatively higher rates of acral and mucosal
      types than in other populations. However, the efficacy of checkpoint inhibitor
      therapies against these melanoma subtypes is not well defined. We analyzed 52
      patients treated with ipilimumab, pembrolizumab, or a combination of both to
      evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients
      with advanced melanoma, particularly those with acral and mucosal types. The
      objective response rates (ORRs) were 0, 25, and 20% for ipilimumab,
      pembrolizumab, and pembrolizumab plus ipilimumab, respectively. Pembrolizumab
      contained therapy was as effective in acral and mucosal melanoma patients (ORR
      26.7 and 20%, respectively) as in non-acral cutaneous melanoma patients (ORR
      26.7%). Baseline lactate dehydrogenase levels and relative lymphocyte counts were
      independent prognostic factors for PFS and OS. The incidences of grade 3-4
      adverse events were 14% in the two monotherapy groups and 30% in the combined
      therapy group. The most frequent adverse events were elevation of
      aminotransferase, skin toxicity, thyroid dysfunction, pyrexia, and fatigue.
      Treatment-related rash or vitiligo was associated with a better prognosis. In
      summary, pembrolizumab-based therapy resulted in meaningful efficacy and good
      tolerability in Chinese patients with melanoma, including those with acral and
      mucosal types.

PMID- 28444426
TI  - Investigation of altered microstructure in patients with drug refractory epilepsy
      using diffusion tensor imaging.
AB  - PURPOSE: The risk of refractory epilepsy can be more dangerous than the adverse
      effect caused by medical treatment. In this study, we employed voxel-wise
      analysis (VWA) and tract-based spatial statistics (TBSS) methods to measure
      microstructural changes using diffusion tensor imaging (DTI) in patients of drug
      refractory epilepsy (DRE) who had been epileptic for more than 10 years. METHODS:
      To examine the specific microstructural abnormalities in DRE patients and its
      difference from medically controlled epilepsy (MCE), we acquired DTI data of 7
      DRE patients, 37 MCE patients, and 31 healthy controls (HCs) using a 3 T MRI
      scanner. Comparisons between epileptic patients and HCs between MCE and DRE
      patients were performed based on calculated diffusion anisotropic indices data
      using VWA and TBSS. RESULTS: Compared to HCs, epileptic patients (including MCE
      and DRE) showed significant DTI changes in the common affected regions based on
      VWA, whereas TBSS found that widespread DTI changes in parts of microstructures
      of bilateral hemispheres were more obvious in the DRE patients than that in the
      MCE patients when compared with HCs. In contrast, significant reduction of
      fractional anisotropy values of thalamo-cortical fibers, including left superior
      temporal gyrus, insular cortex, pre-/post-central gyri, and thalamus, were
      further found in DRE patients compared with MCE. CONCLUSION: The results of
      multiple diffusion anisotropic indices data provide complementary information to
      understand the dysfunction of thalamo-cortical pathway in DRE patients, which may
      be contributors to disorder of language and motor functions. Our current study
      may shed light on the pathophysiology of DRE.

PMID- 28444425
TI  - Pharmacogenetic markers to predict the clinical response to methotrexate in south
      Indian Tamil patients with psoriasis.
AB  - INTRODUCTION: Despite the advent of several new systemic therapies, methotrexate
      remains the gold standard for the treatment of moderate to severe psoriasis.
      However, there exists a significant heterogeneity in individual response to
      methotrexate. There are no consistently reliable markers to predict methotrexate
      treatment response till date. OBJECTIVES: We aimed to demonstrate the association
      of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non
      HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-gamma, IL-2,
      IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the
      methotrexate treatment response in South Indian Tamil patients with psoriasis.
      METHODS: Of the 360 patients recruited, 189 patients with moderate to severe
      psoriasis were treated with methotrexate. Of the 189 patients, 132 patients
      responded to methotrexate and the remaining 57 patients were non-responders. We
      analyzed the association of aforesaid polymorphisms with the methotrexate
      treatment outcome using binary logistic regression. RESULTS: We observed that
      there were significant differences between genotype frequencies of HLA-Cw6 and
      FOXP3 (rs3761548) among the responders compared to non-responders, with
      conservative estimation. We observed that pro-inflammatory cytokines such as IFN
      gamma, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate,
      in comparison to the baseline levels, while the plasma IL-4 levels were increased
      posttreatment. CONCLUSION: Our results serve as preliminary evidence for the
      clinical use of genetic markers as predictors of response to methotrexate in
      psoriasis. This might aid in the future in the development of a point-of-care
      testing (POCT) gene chip, to predict optimal treatment response in patients with
      psoriasis, based on their individual genotypic profile.

PMID- 28444427
TI  - Population pharmacokinetic modelling of doxorubicin and doxorubicinol in children
      with cancer: is there a relationship with cardiac troponin profiles?
AB  - PURPOSE: Anthracyclines are a mainstay of the treatment of several childhood
      malignancies, but their utility is limited by dose-related cardiotoxicity. This
      study is aimed to explore the link between exposure of paediatric cancer patients
      to doxorubicin and its metabolite doxorubicinol, and cardiac troponin I (cTnI).
      METHODS: In a prospective pilot study plasma doxorubicin, doxorubicinol, and cTnI
      concentrations were measured in samples from children undergoing cancer
      chemotherapy. A mixed-effects population pharmacokinetic model for doxorubicin
      and doxorubicinol and in combination with a turn-over model for cTnI were
      developed. RESULTS: Seventeen patients, aged 3.4-14.7 year, treated for a variety
      of cancers had 99 doxorubicin and 119 doxorubicinol concentrations analysed from
      samples drawn between 0.5 and 336 h after the start of the infusion. Eleven
      patients had received previous doses of anthracyclines, with a median cumulative
      prior dose of 90 mg/m2 (range 0-225 mg/m2). The median administered doxorubicin
      dose was 30 mg/m2 (range 25-75 mg/m2). Doxorubicin disposition was described by a
      three-compartment model with first-order elimination and metabolism to
      doxorubicinol. Body surface area was related to all clearance and distribution
      parameters and age further influenced clearance (CL, 58.7 L/h/1.8 m2 for an
      average 8.4-year-old patient). Combined doxorubicin and metabolite exposure
      stimulated a temporary increase in cTnI in plasma, with a concentration of 11.8
      ug/L required to achieve half-maximal effect. Prior cumulative anthracycline
      dosage received by patients was predictive of an increased cTnI baseline prior to
      a new doxorubicin dose. CONCLUSION: Prior anthracycline exposure increased
      baseline cTnI in a dose-dependent manner, consistent with the known cumulative
      risk of anthracycline exposure-induced cardiotoxicity.

PMID- 28444428
TI  - Commentary: Reduction Malarplasty that uses Malar Setback Without Resection of
      Malar Body Strip.

PMID- 28444429
TI  - Hypopharyngeal and upper esophageal ulceration after cervical spine radiotherapy
      concurrent with crizotinib.
AB  - Herein, the authors describe the case of a 31-year-old female patient with
      primary metastatic adenocarcinoma of the lung referred for radiation therapy of
      newly diagnosed intramedullary spinal cord metastasis at C4/5 and an adjacent
      osteolytic lesion. Radiotherapy of the cervical spine level C3 to C5, including
      the whole vertebra, was performed with 30 Gy in 10 fractions. The patient's
      systemic therapy with crizotinib 250 mg twice daily was continued. After 8
      fractions of radiation the patient developed increasing dysphagia. Ulceration of
      the hypopharynx and the upper esophagus were obvious in esophagoscopy and CT.
      Hospitalization for analgesia and percutaneous endoscopic gastrostomy (PEG) was
      required. First oral intake was possible 3 weeks after the onset of symptoms. The
      early onset, severity, and duration of mucositis seemed highly unusual in this
      case. A review of the literature failed to identify any reference to increased
      mucositis after radiation therapy concurrent with crizotinib, although references
      to such an effect with other tyrosine kinase inhibitors (TKI) were found.
      Nevertheless, the authors presume that a considerable risk of unexpected
      interactions exists. When crizotinib and radiotherapy are combined, heightened
      attention toward intensified reactions seems to be warranted.

PMID- 28444430
TI  - Successful treatment of a rare case of ameloblastic fibrosarcoma with radiation
      therapy.
AB  - Sarcomas are rare diseases of the head and neck region, representing around 1% of
      all malignancies. Amongst them, ameloblastic fibrosarcoma (AFS) is of even
      greater rarity, with less than 100 cases reported in the literature.
      Consequently, no standard treatment or guidelines have been made available.
      Surgery is often performed as primary therapy, but may be limited due to
      anatomical or functional reasons. We present a case of AFS successfully treated
      by postoperative radiation therapy. A detailed case study is provided, followed
      by a review of the English-language literature focusing on the role of radiation
      therapy.

PMID- 28444431
TI  - Spinal radiographs in those with back pain-when are they appropriate to diagnose
      vertebral fractures?
AB  - The presence of an osteoporotic vertebral fracture improves fracture risk
      assessment and may change management, so it is vital for healthcare professionals
      to assess patients for the presence or absence of these fractures. This may be
      particularly important in the presence of back pain. However, the correlation
      between low back symptoms and spinal imaging results is poor and the
      pathophysiology of most low back pain is not known, leading to a common
      conclusion that spinal radiographs are not appropriate for the assessment of back
      pain. For individual patients with back pain, spinal radiographs should be
      considered if they have certain features in the history and examination. As well
      as the traditional risk factors for osteoporosis, self-reported descriptives of
      back pain and novel physical examination findings have been shown to make the
      presence of vertebral fractures more likely. Systematic approaches have the
      potential to improve bone health across the population but need to be targeted to
      be cost-effective. Spinal radiographs should be considered for individual older
      patients with back pain if they have certain additional features in the history
      and examination.

PMID- 28444432
TI  - Childhood growth predicts higher bone mass and greater bone area in early old
      age: findings among a subgroup of women from the Helsinki Birth Cohort Study.
AB  - : We examined the associations between childhood growth and bone properties among
      women at early old age. Early growth in height predicted greater bone area and
      higher bone mineral mass. However, information on growth did not improve
      prediction of bone properties beyond that predicted by body size at early old
      age. INTRODUCTION: We examined the associations between body size at birth and
      childhood growth with bone area, bone mineral content (BMC), and areal bone
      mineral density (aBMD) in early old age. METHODS: A subgroup of women (n = 178,
      mean 60.4 years) from the Helsinki Birth Cohort Study, born 1934-1944,
      participated in dual-energy X-ray absorptiometry (DXA) measurements of the lumbar
      spine and hip. Height and weight at 0, 2, 7, and 11 years, obtained from health
      care records, were reconstructed into conditional variables representing growth
      velocity independent of earlier growth. Weight was adjusted for corresponding
      height. Linear regression models were adjusted for multiple confounders. RESULTS:
      Birth length and growth in height before 7 years of age were positively
      associated with femoral neck area (p < 0.05) and growth in height at all age
      periods studied with spine bone area (p < 0.01). Growth in height before the age
      of 7 years was associated with BMC in the femoral neck (p < 0.01) and birth
      length and growth in height before the age of 7 years were associated with BMC in
      the spine (p < 0.05). After entering adult height into the models, nearly all
      associations disappeared. Weight gain during childhood was not associated with
      bone area or BMC, and aBMD was not associated with early growth. CONCLUSIONS:
      Optimal growth in height in girls is important for obtaining larger skeleton and
      consequently higher bone mass. However, when predicting bone mineral mass among
      elderly women, information on early growth does not improve prediction beyond
      that predicted by current height and weight.

PMID- 28444433
TI  - Boundaries of the thoracic paravertebral space: potential risks and benefits of
      the thoracic paravertebral block from an anatomical perspective.
AB  - PURPOSE: Thoracic paravertebral block (TPVB) may be an alternative to thoracic
      epidural analgesia. A detailed knowledge of the anatomy of the TPV-space (TPVS),
      content and adnexa is essential in understanding the clinical consequences of
      TPVB. The exploration of the posterior TPVS accessibility in this study allows
      (1) determination of the anatomical boundaries, content and adnexa, (2)
      description of an ultrasound-guided spread of low and high viscous liquid.
      METHODS: In two formalin-fixed specimens, stratification of the several layers
      and the 3D-architecture of the TPVS were dissected, observed and photographed. In
      a third unembalmed specimen, ultrasound-guided posterolateral injections at
      several levels of the TPVS were performed with different fluids. RESULTS: TPVS
      communicated with all surrounding spaces including the segmental dorsal
      intercostal compartments (SDICs) and the prevertebral space. TPVS transitions to
      the SDICs were wide, whereas the SDICs showed narrowed transitions to the lateral
      intercostal spaces at the costal angle. Internal subdivision of the TPVS in a
      subendothoracic and an extra-pleural compartment by the endothoracic fascia was
      not observed. Caudally injected fluids spread posteriorly to the
      costodiaphragmatic recess, showing segmental intercostal and slight prevertebral
      spread. CONCLUSIONS: Our detailed anatomical study shows that TPVS is a potential
      space continuous with the SDICs. The separation of the TPVS in a subendothoracic
      and an extra-pleural compartment by the endothoracic fascia was not observed.
      Based on the ultrasound-guided liquid spread we conclude that the use of a more
      lateral approach might increase the probability of intravascular puncture or
      catheter position.

PMID- 28444434
TI  - Quantitative anatomy of the primary ossification center of the femoral shaft in
      human fetuses.
AB  - PURPOSE: Early clinical distinction of congenital defects in the femur is
      extremely important, as it determines the prognosis of the development of the
      lower limb. This study was performed to quantitatively examine the primary center
      of ossification in the femoral shaft with respect to its linear, planar, and
      volumetric parameters. MATERIALS AND METHODS: Using methods of CT, digital-image
      analysis, and statistics, the size of the primary ossification center of the
      femoral shaft in 47 spontaneously aborted human fetuses aged 17-30 weeks was
      studied. RESULTS: With no sex and laterality differences, the best fit growth
      dynamics for femoral shaft ossification center was modelled by the following
      functions: y = 5.717 + 0.040 * (age)2 +/- 2.905 (R 2 = 0.86) for its length, y = 
      3.579 + 0.368 * age +/- 0.529 (R 2 = 0.88) for its proximal transverse diameter,
      y = -1.105 + 0.187 * age +/- 0.309 (R 2 = 0.84) for its middle transverse
      diameter, y = -2.321 + 0.323 * age +/- 0.558 (R 2 = 0.83) for its distal
      transverse diameter, y = -50.306 + 0.308 * (age)2 +/- 18.289 (R 2 = 0.90) for its
      projection surface area, and y = -91.458 + 0.390 * (age)3 +/- 92.146 (R 2 = 0.88)
      for its volume. CONCLUSIONS: The size of the femoral shaft ossification center
      displays neither sex nor laterality differences. The ossification center in the
      femoral shaft follows quadratic functions with respect to its length and
      projection surface area, linear functions with respect to its proximal, middle,
      and distal transverse diameters, and a cubic function with respect to its volume.
      The obtained morphometric data of the femoral shaft ossification center are
      considered normative for respective prenatal weeks and may be of relevance in
      both the estimation of fetal ages and the ultrasound diagnostics of congenital
      defects.

PMID- 28444436
TI  - Acute effects of static stretching on muscle-tendon mechanics of quadriceps and
      plantar flexor muscles.
AB  - PURPOSE: This study aimed to determine the acute effects of static stretching on
      stiffness indexes of two muscle groups with a contrasting difference in muscle
      tendon proportion. METHODS: Eleven active males were tested on an isokinetic
      dynamometer during four sessions randomly presented. Two sessions were dedicated
      to quadriceps and the two others to triceps surae muscles. Before and immediately
      after the stretching procedure (5 * 30 s), gastrocnemius medialis and rectus
      femoris fascicle length and myotendinous junction elongation were determined
      using ultrasonography. Passive and maximal voluntary torques were measured.
      Fascicle and myotendinous junction stiffness indexes were calculated. RESULTS:
      After stretching, maximal voluntary torque similarly decreased for both muscle
      groups. Passive torque significantly decreased on triceps surae and remained
      unchanged on quadriceps muscles. Fascicle length increased similarly for both
      muscles. However, myotendinous junction elongation remained unchanged for
      gastrocnemius medialis and increased significantly for rectus femoris muscle.
      Fascicle stiffness index significantly decreased on medial gastrocnemius and
      remained unchanged on rectus femoris muscle. In contrast, myotendinous junction
      stiffness index similarly decreased on both muscles. CONCLUSION: Depending on the
      muscle considered, the present results revealed different acute stretching
      effects. This muscle dependency appeared to affect primarily fascicle stiffness
      index rather than the myotendinous junction.

PMID- 28444435
TI  - Genetic sex determination in Astatotilapia calliptera, a prototype species for
      the Lake Malawi cichlid radiation.
AB  - East African cichlids display extensive variation in sex determination systems.
      The species Astatotilapia calliptera is one of the few cichlids that reside both
      in Lake Malawi and in surrounding waterways. A. calliptera is of interest in
      evolutionary studies as a putative immediate outgroup species for the Lake Malawi
      species flock and possibly as a prototype ancestor-like species for the
      radiation. Here, we use linkage mapping to test association of sex in A.
      calliptera with loci that have been previously associated with genetic sex
      determination in East African cichlid species. We identify a male heterogametic
      XY system segregating at linkage group (LG) 7 in an A. calliptera line that
      originated from Lake Malawi, at a locus previously shown to act as an XY sex
      determination system in multiple species of Lake Malawi cichlids. Significant
      association of genetic markers and sex produce a broad genetic interval of
      approximately 26 megabases (Mb) using the Nile tilapia genome to orient markers;
      however, we note that the marker with the strongest association with sex is near
      a gene that acts as a master sex determiner in other fish species. We demonstrate
      that alleles of the marker are perfectly associated with sex in Metriaclima
      mbenjii, a species from the rock-dwelling clade of Lake Malawi. While we do not
      rule out the possibility of other sex determination loci in A. calliptera, this
      study provides a foundation for fine mapping of the cichlid sex determination
      gene on LG7 and evolutionary context regarding the origin and persistence of the
      LG7 XY across diverse, rapidly evolving lineages.

PMID- 28444437
TI  - Range limitation in hip internal rotation and fifth metatarsal stress fractures
      (Jones fracture) in professional football players.
AB  - PURPOSE: To identify unknown risk factors associated with fifth metatarsal stress
      fracture (Jones fracture). METHODS: A case-controlled study was conducted among
      male Japanese professional football (soccer) players with (N = 20) and without (N
      = 40) a history of Jones fracture. Injury history and physical examination data
      were reviewed, and the two groups were compared. Univariate and multivariate
      logistic regression controlling for age, leg dominance and body mass index were
      used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to describe
      the association between physical examination data and the presence or absence of
      Jones fractures. RESULTS: From 2000 to 2014, among 162 professional football club
      players, 22 (13.6%; 21 Asians and one Caucasian) had a history of Jones fracture.
      Thirteen out of 22 (60%) had a Jones fracture in their non-dominant leg. The mean
      range of hip internal rotation (HIR) was restricted in players with a history of
      Jones fracture [25.9 degrees  +/- 7.5 degrees , mean +/- standard deviation (SD)]
      compared to those without (40.4 degrees  +/- 11.1 degrees , P < 0.0001). Logistic
      regression analyses demonstrated that HIR limitation increased the risk of a
      Jones fracture (OR = 3.03, 95% CI 1.45-6.33, P = 0.003). Subgroup analysis using
      data prior to Jones fracture revealed a causal relationship, such that players
      with a restriction of HIR were at high risk of developing a Jones fracture [Crude
      OR (95% CI) = 6.66 (1.90-23.29), P = 0.003, Adjusted OR = 9.91 (2.28-43.10), P =
      0.002]. In addition, right HIR range limitation increased the risks of developing
      a Jones fracture in the ipsilateral and the contralateral feet [OR = 3.11 (1.35
      7.16) and 2.24 (1.22-4.12), respectively]. Similarly, left HIR range limitation
      increased the risks in the ipsilateral or the contralateral feet [OR (95% CI) =
      4.88 (1.56-15.28) and 2.77 (1.08-7.08), respectively]. CONCLUSION: The
      restriction of HIR was associated with an increased risk of developing a Jones
      fracture. Since the HIR range is a modifiable factor, monitoring and improving
      the HIR range can lead to prevent reducing the occurrence of this fracture. LEVEL
      OF EVIDENCE: III.

PMID- 28444438
TI  - Effect and safety of early weight-bearing on the outcome after open-wedge high
      tibial osteotomy: a systematic review and meta-analysis.
AB  - INTRODUCTION: The purpose of this systematic review and meta-analysis was to
      evaluate the effectiveness and safety of early weight-bearing by comparing
      clinical and radiological outcomes between early and traditional delayed weight
      bearing after OWHTO. MATERIALS AND METHODS: A rigorous and systematic approach
      was used. The methodological quality was also assessed. Results that are possible
      to be compared in two or more than two articles were presented as forest plots. A
      95% confidence interval was calculated for each effect size, and we calculated
      the I 2 statistic, which presents the percentage of total variation attributable
      to the heterogeneity among studies. The random-effects model was used to
      calculate the effect size. RESULTS: Six articles were included in the final
      analysis. All case groups were composed of early full weight-bearing within 2
      weeks. All control groups were composed of late full weight-bearing between 6
      weeks and 2 months. Pooled analysis was possible for the improvement in Lysholm
      score, but there was no statistically significant difference shown between
      groups. Other clinical results were also similar between groups. Four studies
      reported mechanical femorotibial angle (mFTA) and this result showed no
      statistically significant difference between groups in the pooled analysis.
      Furthermore, early weight-bearing showed more favorable results in some
      radiologic results (osseointegration and patellar height) and complications
      (thrombophlebitis and recurrence). CONCLUSION: Our analysis supports that early
      full weight-bearing after OWHTO using a locking plate leads to improvement in
      outcomes and was comparable to the delayed weight-bearing in terms of clinical
      and radiological outcomes. On the contrary, early weight-bearing was more
      favorable with respect to some radiologic parameters and complications compared
      with delayed weight-bearing.

PMID- 28444440
TI  - Paradoxical undressing associated with subarachnoid hemorrhage in a non
      hypothermia case?
AB  - Paradoxical undressing is a phenomenon characterizing some fatal hypothermia
      cases. The victims, despite low environmental temperatures, paradoxically remove
      their clothes due to a sudden feeling of warmth. In this report, we describe a
      case of suspected paradoxical undressing in a non-hypothermia case. The victim, a
      51-year-old Caucasian man, was found dead wearing only sneakers and socks. All
      other clothing was found in his car. Postmortem investigations allowed the
      hypothesis of hypothermia to be ruled out and revealed the presence of a ruptured
      cerebral aneurysm that caused a subarachnoid hemorrhage, the latter responsible
      for the death. The absence of any elements suggesting a voluntary undressing or
      any third party's DNA profile or involvement along with the possibility that the
      subarachnoid hemorrhage might have determined a hypothalamic injury, somehow
      rendered conceivable the hypothesis of an inappropriate feeling of warmth due to
      hemorrhage-induced dysregulation of the hypothalamic temperature-regulating
      centers.

PMID- 28444439
TI  - Back to the Future - Part 2. Post-mortem assessment and evolutionary role of the
      bio-medicolegal sciences.
AB  - Part 2 of the review "Back to the Future" is dedicated to the evolutionary role
      of the bio-medicolegal sciences, reporting the historical profiles, the state of
      the art, and prospects for future development of the main related techniques and
      methods of the ancillary disciplines that have risen to the role of "autonomous"
      sciences, namely, Genetics and Genomics, Toxicology, Radiology, and Imaging,
      involved in historic synergy in the "post-mortem assessment," together with the
      mother discipline Legal Medicine, by way of its primary fundament, universally
      denominated as Forensic Pathology. The evolution of the scientific research and
      the increased accuracy of the various disciplines will be oriented towards the
      elaboration of an "algorithm," able to weigh the value of "evidence" placed at
      the disposal of the "justice system" as real truth and proof.

PMID- 28444442
TI  - High accumulation of anthocyanins via the ectopic expression of AtDFR confers
      significant salt stress tolerance in Brassica napus L.
AB  - KEY MESSAGE: The ectopic expression of AtDFR results in increased accumulation of
      anthocyanins leading to enhanced salinity and drought stress tolerance in B.
      napus plants. Flavonoids with antioxidant effects confer many additional benefits
      to plants. Evidence indicates that flavonoids, including anthocyanins, protect
      tissues against oxidative stress from various abiotic stressors. We determined
      whether increases in anthocyanins increased abiotic stress tolerance in Brassica
      napus, because the values of B. napus L. and its cultivation area are increasing
      worldwide. We overexpressed Arabidopsis dihydroflavonol-4-reductase (DFR) in B.
      napus. Increased DFR transcript levels for AtDFR-OX B. shoots correlated with
      higher anthocyanin accumulation. AtDFR-OX Brassica shoots exhibited lower
      reactive oxygen species (ROS) accumulation than wild-type (WT) shoots under high
      NaCl and mannitol concentrations. This was corroborated by 3,3-diaminobenzidine
      staining for ROS scavenging activity in 1,1-diphenyl-2-picryl-hydrazyl assays.
      Shoots of the AtDFR-OX B. napus lines grown in a high salt medium exhibited
      enhanced salt tolerance and higher chlorophyll content than similarly grown WT
      plants. Our observations suggested that the AtDFR gene can be effectively
      manipulated to modulate salinity and drought stress tolerance by directing to
      high accumulation of anthocyanins in oilseed plants.

PMID- 28444441
TI  - The activity of the rectal gland of the North Pacific spiny dogfish Squalus
      suckleyi is glucose dependent and stimulated by glucagon-like peptide-1.
AB  - Elasmobranchs possess a specialised organ, the rectal gland, which is responsible
      for excreting sodium chloride via the posterior intestine. Previous work has
      indicated that the gland may be activated by a number of hormones, some of which
      are likely related to the salt or volume loads associated with feeding.
      Furthermore, evidence exists for the gland being glucose dependent which is
      atypical for an elasmobranch tissue. In this study, the presence of sodium
      glucose co-transporters (SGLTs) in the rectal gland and their regulation by
      feeding were investigated. In addition, the hypothesis of glucose dependence was
      examined through the use of glucose transporter (GLUT and SGLT) inhibitors,
      phlorizin, Indinavir, and STF-31 and their effect on secretion by the rectal
      gland. Finally, the effects on rectal gland activity of insulin, glucagon, and
      glucagon-like peptide-1, hormones typically involved in glucoregulation, were
      examined. The results showed that sglt1 mRNA is present in the gland, and there
      was a significant reduction in sglt1 transcript abundance 24 h post-feeding. An
      almost complete suppression of chloride secretion was observed when glucose
      uptake was inhibited, confirming the organ's glucose dependence. Finally,
      perfusion with dogfish GLP-1 (10 nmol L-1), but not dogfish glucagon, was shown
      to markedly stimulate the activity of the gland, increasing chloride secretion
      rates above baseline by approximately 16-fold (p < 0.001). As GLP-1 is released
      from the intestine upon feeding, we propose that this may be the primary signal
      for activation of the rectal gland post-feeding.

PMID- 28444443
TI  - [New approaches for the prevention of actinic keratosis].
AB  - Actinic keratosis is one of the most common skin diseases. Because of the ongoing
      demographic changes, it is anticipated that the incidence will further increase.
      Prevention of actinic keratoses is thus of great importance. By far the most
      important cause of actinic keratoses is the chronic cumulative irradiation of
      human skin with ultraviolet B and A radiation from natural sunlight. There is no
      doubt that use of sunscreens is effective in preventing actinic keratoses. Recent
      studies indicate that in high-risk groups the regular use of medical devices
      which are characterized by a very high SPF and which contain liposomally
      encapsulated DNA repair enzymes are effective in preventing the development of
      new actinic keratoses even when field cancerization is already present in human
      skin. There is also evidence that oral photoprotective strategies based on the
      regular intake of vitamin B3 may be used to prevent actinic keratoses.

PMID- 28444444
TI  - Bioinformatic and expression analyses on carotenoid dioxygenase genes in fruit
      development and abiotic stress responses in Fragaria vesca.
AB  - Carotenoid dioxygenases, including 9-cis-epoxycarotenoid dioxygenases (NCEDs) and
      carotenoid cleavage dioxygenases (CCDs), can selectively cleave carotenoids into
      various apocarotenoid products that play important roles in fleshy fruit
      development and abiotic stress response. In this study, we identified 12
      carotenoid dioxygenase genes in diploid strawberry Fragaria vesca, and explored
      their evolution with orthologous genes from nine other species. Phylogenetic
      analyses suggested that the NCED and CCDL groups moderately expanded during their
      evolution, whereas gene numbers of the CCD1, CCD4, CCD7, and CCD8 groups
      maintained conserved. We characterized the expression profiles of FveNCED and
      FveCCD genes during flower and fruit development, and in response to several
      abiotic stresses. FveNCED1 expression positively responded to osmotic, cold, and
      heat stresses, whereas FveNCED2 was only induced under cold stress. In contrast,
      FveNCED2 was the unique gene highly and continuously increasing in receptacle
      during fruit ripening, which co-occurred with the increase in endogenous abscisic
      acid (ABA) content previously reported in octoploid strawberry. The differential
      expression patterns suggested that FveNCED1 and FveNCED2 were key genes for ABA
      biosynthesis in abiotic stress responses and fruit ripening, respectively.
      FveCCD1 exhibited the highest expression in most stages of flower and fruit
      development, while the other FveCCDs were expressed in a subset of stages and
      tissues. Our study suggests distinct functions of FveNCED and FveCCD genes in
      fruit development and stress responses and lays a foundation for future study to
      understand the roles of these genes and their metabolites, including ABA and
      other apocarotenoid products, in the growth and development of strawberry.

PMID- 28444445
TI  - Acquired cystic kidney disease: an under-recognized condition in children with
      end-stage renal disease.
AB  - Acquired cystic kidney disease (ACKD) is a condition that occurs predominantly in
      patients with end-stage renal disease (ESRD). In contrast to hereditary cystic
      kidney disease, ACKD is characterized by the presence of multiple small cysts in
      bilaterally small kidneys. Limited pediatric data suggest a high incidence (21.6
      45.8%) of ACKD in children on dialysis, comparable to that in adults, with an
      increased frequency associated with a longer duration of dialysis. Recent
      research has shed light on the pathogenesis of ACKD, such as activation of proto
      oncogenes. Although most patients with ACKD are asymptomatic, the condition can
      be complicated by renal cell carcinoma. Routine surveillance should therefore be
      considered in at-risk populations.

PMID- 28444447
TI  - William G. Niederland (1904-1993).

PMID- 28444446
TI  - Comparison of the clinical and cognitive features of genetically positive ALS
      patients from the largest tertiary center in Serbia.
AB  - Discovering novel mutations in C9orf72, FUS, ANG, and TDP-43 genes in ALS
      patients arises necessities for better clinical characterizations of these
      subjects. The aim is to determine clinical and cognitive profile of genetically
      positive Serbian ALS patients. 241 ALS patients were included in the study (17
      familiar and 224 apparently sporadic). The following genes were analyzed: SOD1,
      C9orf72, ANG, FUS, and TDP-43. An extensive battery of classic neuropsychological
      tests was used in 27 ALS patients (22 SOD1 positive and 5 SOD1 negative) and 82
      healthy controls (HCs). Overall 37 (15.4%) of 241 ALS patients carried mutations
      in tested genes-among 17 familiar ALS patients 16 (94.1%) were positive and among
      224 apparently sporadic 21 (9.4%) had causative mutation. Mutations in SOD1 gene
      were the most common, representing 27 (73.0%) of all genetically positive ALS
      patients. The main clinical characteristics of SOD1 positive patients were:
      spinal onset in lower extremities, common sphincter and sensitive disturbances,
      and dysexecutive syndrome. Within SOD1 positive patients, we noticed somewhat
      earlier onset in patients with A145G, sensory and sphincter disturbances were
      dominant in patients with L144F, while D90A patients had significant sensory
      involvement. SOD1 negative group consisted of ten (27.0%) patients (six C9orf72,
      two ANG, one TDP-43, and one patient baring triple FUS, C9orf72 expansion, and
      ANG variants). Bulbar involvement and more extensive neuropsychological
      impairment (including executive, visuospatial, and memory difficulties) were the
      main features of SOD1 negative cohort. Our results suggest that meaningful
      clinical suspicion of certain ALS genotype might be made based on thorough
      clinical evaluation of patients.

PMID- 28444448
TI  - The 5' untranslated region of potato SBgLR gene contributes to pollen-specific
      expression.
AB  - MAIN CONCLUSION: The 5'UTR of SBgLR enhances gene expression by regulating both
      its transcription and translation. SBgLR (Solanum tuberosum genomic lysine rich)
      is a pollen-specific gene in Solanum tuberosum that encodes a microtubule
      associated protein. The region from -85 to +180 (transcription start site at +1)
      was determined to be critical for specific expression in pollen grains. Transient
      and stable expression assays showed that the 5'UTR (from +1 to +184) enhanced
      gene expression in all detected tissues of transgenic tobacco. Deletion analysis
      demonstrated that the secondary structure of the 5'UTR had no effect on pollen
      specific SBgLR expression, while the region from +31 to +60 was crucial. Further
      investigation indicated that mRNA expression was slightly decreased when the +31
      to +60 region was deleted, but the mRNA decay rate remained unchanged. Mutation
      analysis also confirmed that the pollen-specific element TTTCT, located at +37,
      played an important role in pollen-specific expression. Using yeast one-hybrid
      screening, we isolated a DNA-binding with one finger (Dof) protein gene (StDof23)
      and an AT-hook motif nuclear-localized (AHL) protein gene (StAHL) from potato
      pollen. Further investigation indicated that StDof23 interacted with and
      positively regulated the +31 to +60 region; moreover, StAHL interacted with and
      negatively regulated the -49 to +60 region. These results demonstrate that the
      5'UTR not only enhanced gene expression but also altered the tissue-specific
      expression pattern by regulating both transcription and translation.

PMID- 28444449
TI  - Application of palliative ventilation: potential and clinical evidence in
      palliative care.

PMID- 28444450
TI  - SGNH hydrolase-type esterase domain containing Cbes-AcXE2: a novel and
      thermostable acetyl xylan esterase from Caldicellulosiruptor bescii.
AB  - Caldicellulosiruptor bescii, the most thermophilic cellulolytic bacterium, is
      rich in hydrolytic and accessory enzymes that can degrade untreated biomass, but
      the precise role of many these enzymes is unknown. One of such enzymes is a
      predicted GDSL lipase or esterase encoded by the locus Athe_0553. In this study,
      this probable esterase named as Cbes-AcXE2 was overexpressed in Escherichia coli.
      The Ni-NTA affinity purified enzyme exhibited an optimum pH of 7.5 at an optimum
      temperature of 70  degrees C. Cbes-AcXE2 hydrolyzed p-nitrophenyl (pNP) acetate,
      pNP-butyrate, and phenyl acetate with approximately equal efficiency. The
      specific activity and K M for the most preferred substrate, phenyl acetate, were
      142 U/mg and 0.85 mM, respectively. Cbes-AcXE2 removed the acetyl group of
      xylobiose hexaacetate and glucose pentaacetate like an acetyl xylan esterase
      (AcXE). Bioinformatics analyses suggested that Cbes-AcXE2, which carries an SGNH
      hydrolase-type esterase domain, is a member of an unclassified carbohydrate
      esterase (CE) family. Moreover, Cbes-AcXE2 is evolutionarily and biochemically
      similar to an unclassified AcXE, Axe2, of Geobacillus stearothermophilus. Thus,
      we proposed a novel family of carbohydrate esterase for both Cbes-AcXE2 and Axe2.

PMID- 28444451
TI  - New tumor entities in the 4th edition of the World Health Organization
      classification of head and neck tumors: Nasal cavity, paranasal sinuses and skull
      base.
AB  - The World Health Organization recently published the 4th edition of the
      Classification of Head and Neck Tumors, including several new entities, emerging
      entities, and significant updates to the classification and characterization of
      tumor and tumor-like lesions, specifically as it relates to nasal cavity,
      paranasal sinuses, and skull base in this overview. Of note, three new entities
      (NUT carcinoma, seromucinous hamartoma, biphenotypic sinonasal sarcoma,) were
      added to this section, while emerging entities (SMARCB1-deficient carcinoma and
      HPV-related carcinoma with adenoid cystic-like features) and several tumor-like
      entities (respiratory epithelial adenomatoid hamartoma, chondromesenchymal
      hamartoma) were included as provisional diagnoses or discussed in the setting of
      the differential diagnosis. The sinonasal tract houses a significant diversity of
      entities, but interestingly, the total number of entities has been significantly
      reduced by excluding tumor types if they did not occur exclusively or
      predominantly at this site or if they are discussed in detail elsewhere in the
      book. Refinements to nomenclature and criteria were provided to sinonasal
      papilloma, borderline soft tissue tumors, and neuroendocrine neoplasms. Overall,
      the new WHO classification reflects the state of current understanding for many
      relatively rare neoplasms, with this article highlighting the most significant
      changes.

PMID- 28444452
TI  - Ebola virus disease in children during the 2014-2015 epidemic in Guinea: a
      nationwide cohort study.
AB  - : The most recent epidemic of Ebola virus disease (EVD) has resulted in more than
      11,000 deaths in West Africa. It has threatened child health in the affected
      countries, including Guinea. This nationwide retrospective cohort study included
      all children under 20 years of age with laboratory-confirmed EVD in Guinea during
      the 2014-2015 Ebola outbreak for analysis. Of 8,448 children with probable or
      suspected EVD, 695 cases were laboratory-confirmed EVD. The overall case fatality
      rate (CFR) was 62.9%. Pediatric patients with younger age had a significantly
      higher rate of death (adjusted OR = 0.995; 95%CI = 0.990-1.000; p = 0.046), with
      the highest CFR of 82.9% in children aged less than 5 years. Fever (91%), fatigue
      (87%), and gastrointestinal signs and symptoms (70%) were common clinical
      features on admission of the pediatric patients, while bleeding signs were not
      occurring often (24%). None of clinical features and epidemiologic risk factors
      for Ebola were associated with mortality outcome in our cohort study. CONCLUSION:
      EVD is a major threat to child health, especially among children under 5 years of
      age. To date, none of demographic and clinical features, except younger age, have
      been consistently shown to affect mortality outcome in children infected with
      Ebola virus. What is Known: * The 2014-2015 West Africa Ebola epidemic is the
      largest and most widespread outbreak of Ebola virus disease (EVD) in history,
      with more than 11,000 deaths in Guinea, Liberia, and Sierra Leone. * During
      ongoing outbreak investigations, it is suggested that young children aged less
      than 5 years are particularly vulnerable and highly susceptible to death. What is
      New: * Demographic and clinical characteristics of the nationwide cohort of
      pediatric patients with laboratory-confirmed EVD in Guinea are reported. * The
      results confirm the high rate of death among EVD children under 5 years of age,
      while none of demographic and clinical features, except younger age, could serve
      as a predictor of mortality outcome in pediatric patients with EVD.

PMID- 28444453
TI  - Bizarre soft tissue tumour on the gluteus muscle: a case report of spontaneous
      chronic expanding haematoma.
AB  - Chronic expanding haematoma (CEH) is rare and refers to a gradually increasing
      haematoma that is not absorbed after surgery and trauma. This report highlights
      unusual mass occurring on the gluteus muscle, and the aim is to indicate the
      diagnostic method. It is necessary to consider the mechanism of the occurrence
      and to know the characters of CEH. The patient was a 51-year-old man who had
      noticed a soft mass on his right hip. The mass had gradually increased to 10 cm
      in size over the year. CT images revealed a haematoma. However, MRI showed a rare
      biphasic fluid-fluid layer inside the mass and indicated a different pattern
      compared with that of a normal haematoma. Because the mass was affecting the
      patient's social life, and the diagnosis was difficult to confirm, surgical
      treatment was elected. Intraoperatively, the mass contained a large amount of a
      brown mud-like substance and showed the bizarre appearance inside. The mass was
      diagnosed as CEH based on both the clinical findings and the histopathological
      diagnosis. The patient had no traumatic event and no previous surgery. In the
      absence of the clinical history and the unique imaging findings, it was difficult
      to diagnose the mass as CEH. It is important to clarify a patient's underlying
      disease, history, and lifestyle and to consider any correlation between the mass
      location and the patient's condition carefully. Considering the character of the
      mass and the lack of a preoperative definitive diagnosis, we recommend performing
      complete surgical resection.

PMID- 28444454
TI  - Influence of the contralateral hip state after total hip arthroplasty on patient
      reported outcomes measured with the Forgotten Joint Score-12.
AB  - PURPOSE: The purpose of this study was to examine the influence of the
      contralateral hip state on postoperative assessment using the Forgotten Joint
      Score-12 (FJS-12) in comparison with the McMaster Universities Osteoarthritis
      Index (WOMAC) and the Japanese Orthopaedic Association Hip Disease Evaluation
      Questionnaire (JHEQ). METHODS: One hundred and thirty-four hips underwent total
      hip arthroplasty (THA) between 2014 and 2015. Of these, the subjects were 106
      hips with degenerative hip arthrosis as a primary disease for whom initial THA
      was performed on the affected side. The WOMAC and JHEQ were investigated before
      surgery and 1 month, 6 months, and 1 year after surgery. The FJS-12 was examined
      1 month, 6 months, and 1 year after surgery. RESULTS: We divided the subjects
      into three groups based on the state of the contralateral hip, which was not
      surgically treated in this study: healthy (n = 43), THA (n = 31), and OA (n = 31)
      groups. One year after surgery, the mean FJS-12 scores in the healthy, THA, and
      OA groups were 69.1, 52.8, and 68.0 points, respectively. In the THA group, the
      score was significantly lower than in the healthy and OA group. There were no
      significant differences in WOMAC and JHEQ scores among the three groups.
      CONCLUSIONS: The FJS-12 score in the presence of an arthroplasty on the
      contralateral side was more markedly influenced by the contralateral hip state
      compared with that in the presence of contralateral painful OA. This result
      suggests that it is necessary to understand the characteristics of PROs and
      utilize them for post-THA assessment.

PMID- 28444455
TI  - Prevalence, predictors, and prognostic implications of residual impairment of
      functional capacity after transcatheter aortic valve implantation.
AB  - BACKGROUND: Patients with degenerative aortic stenosis (AS) referred for
      transcatheter aortic valve implantation (TAVI) typically have advanced cardiac
      and vascular adverse remodeling and multiple comorbidities and, therefore, might
      not recover a normal functional capacity after valve replacement. We sought to
      investigate the prevalence, the predictors, and the prognostic impact of residual
      impairment of functional capacity after TAVI. METHODS AND RESULTS: Out of 790
      patients undergoing TAVI with impaired functional capacity (NYHA II-IV) at
      baseline, NYHA functional class improved in 592 (86.5%) and remained
      unchanged/worsened in 92 (13.5%) at follow-up [median (IQR): 419 (208-807) days]
      after TAVI. Normal functional capacity (NYHA I) was recovered in 65.5% (n = 448)
      of patients, while the rest had variable degrees of residual impairment. On
      multivariable regression analysis, atrial fibrillation [odds ratio-OR, 2.08 (1.21
      3.58), p = 0.008], low-flow-low-gradient AS [OR, 1.97 (1.09-3.57), p = 0.026],
      chronic obstructive pulmonary disease [OR, 1.92 (1.19-3.12), p = 0.008], and
      lower hemoglobin at baseline [OR, 1.11 (1.01-1.21) for each g% decrement, p =
      0.036] were independently associated with residual impairment of functional
      capacity. All-cause and cardiac mortality were significantly higher in those with
      residual impairment of functional capacity than in those in NYHA I class [hazard
      ratio-HR: 2.37 (95% CI: 1.51-3.72), p < 0.001 and 2.16 (95% CI: 1.08-4.35), p =
      0.030, respectively]. Even mild residual functional impairment (NYHA II) was
      associated with a higher all-cause [HR: 2.02 (95% CI: 1.10-3.72), p = 0.023] and
      cardiac [HR: 2.08 (95% CI: 1.42-3.07), p < 0.001] mortality. CONCLUSION: Residual
      impairment of functional capacity is common after TAVI and is independently
      associated with increased mortality. Predictors of residual impairment of
      functional status are predominantly patient-rather than procedure-related.

PMID- 28444456
TI  - Free leucine supplementation during an 8-week resistance training program does
      not increase muscle mass and strength in untrained young adult subjects.
AB  - The purpose of this study was to examine the effects of free leucine
      supplementation on changes in skeletal muscle mass and strength during a
      resistance training (RT) program in previously untrained, young subjects. In a
      double-blind, randomized, placebo-controlled study, 20 healthy young (22 +/- 2
      years) participants were assigned to two groups: a placebo-supplement group (PLA,
      N = 10) or a leucine-supplement group (LEU, N = 10). Both groups underwent an 8
      week hypertrophic RT program (2 days/week), consuming an equivalent amount of
      leucine (3.0 g/day in a single post-training dose) or placebo (cornstarch).
      Quadriceps muscle strength, cross-sectional area (CSA) of the vastus lateralis
      (VL), and rectus femoris (RF), as well as the habitual dietary intake were
      assessed before and after the 8-week intervention period. There was a similar
      improvement in muscle strength (Leg press, LEU: +33% vs. PLA: +37%; P > 0.05, and
      knee extension, LEU: +31% vs. PLA: 34%; P > 0.05) and CSA (VL, LEU: 8.9% vs. PLA:
      9.6%; P > 0.05, and RF, LEU: +21.6% vs. PLA: + 16.4%; P > 0.05) in the both
      groups from pre- to post-training. In addition, there was no significant (P >
      0.05) difference in daily dietary intake between the LEU and PLA groups before
      and after the intervention period. Free leucine supplementation (3.0 g/day post
      training) does not increase muscle strength or CSA during RT in healthy young
      subjects consuming adequate dietary protein intake.

PMID- 28444457
TI  - Social cognition and idiopathic isolated cervical dystonia.
AB  - For a long time, cervical dystonia (CD) has been characterised only by
      disturbances in motor functioning. Despite accumulating evidence for
      symptomatology in various non-motor domains, to date no study has investigated
      social cognition in CD. The aim of this study was to compare performance of CD
      patients and healthy controls in neurocognitive and socio-cognitive domain.
      Twenty-five non-depressed patients with CD and 26 healthy controls underwent
      neuropsychological testing. This involved assessment of cognitive status (general
      intellect, verbal memory, and executive function), and socio-cognitive functions
      using a Theory of mind task and self-report on empathy and emotion regulation. In
      comparison to controls, CD patients displayed significantly decreased cognitive
      abilities, particularly in executive function and verbal memory tasks.
      Difficulties in inferring mental states on both cognitive and affective levels
      were also observed. The largest discrepancies were detected in understanding
      intentionality in others. Poorer performance in cognitive and socio-cognitive
      tasks was unrelated to severity of the disease. This is the first evidence of
      compromised socio-cognitive functions in CD patients, highlighting this domain as
      another facet of non-motor symptoms of this disease. Future studies should
      advance our understanding of the extent, nature, and time course of these
      deficits in other aspects of social cognition in this patient population.

PMID- 28444458
TI  - The potential of eHealth in otorhinolaryngology-head and neck surgery: patients'
      perspectives.
AB  - The use of modern information and communication technologies (ICT) in daily life
      has significantly increased during the last several years. These essential online
      technologies have also found their way into the healthcare system. The use of
      modern ICT for health reasons can be summarized by the term 'eHealth'. Despite
      the potential importance of eHealth in the field of otorhinolaryngology (ORL),
      there is little understanding of patients' attitudes towards the deeper
      integration of these technologies into intersectoral care. The aim of this study
      was to gain a better understanding of patients' attitudes towards the use of
      modern ICT for intersectoral communication and information transfer in the field
      of ORL. Therefore, a structured interview was developed by an interdisciplinary
      team of otorhinolaryngologists, public health researchers, and information
      technology (IT) specialists. Overall, 211 ORL patients were interviewed at the
      Department of Otorhinolaryngology-Head and Neck Surgery, Tuebingen University
      Hospital, Germany, and 203 of these patients completed the interview. This study
      revealed ORL patients' perspectives on the potential of eHealth, especially for
      appointment scheduling, appointment reminders, and intersectoral communication of
      personal medical information. Furthermore, this study provides evidence that data
      security and the impacts of eHealth on the physician-patient relationship and on
      treatment quality warrant special attention in future research.

PMID- 28444459
TI  - Some of the earliest depictions of the human spine: a glimpse into European
      history.
AB  - INTRODUCTION: Drawings of the human form have a history almost as old as mankind
      itself. However, illustrations of the human spine as seen with the vertebral
      column were not seen until much later. This paper reviews some of the early
      European depictions of the human vertebral column from the twelfth (e.g.,
      Funfbilderserie "Bone-Man": 1152 A.D.) and thirteenth (e.g., Ashmole 1292)
      centuries. Man's understanding of his body has evolved over hundreds of years.
      CONCLUSIONS: This glimpse into our past and early drawings of the human spine
      illustrate how this particular anatomical structure was perceived almost a
      millennium ago and would not be structurally correct renditions until Leonardo da
      Vinci in the fifteenth century.

PMID- 28444460
TI  - Hydrocephalus: a rare initial manifestation of sporadic intramedullary
      hemangioblastoma : Intramedullary hemangioblastoma presenting as hydrocephalus.
AB  - BACKGROUND: Intramedullary hemangioblastomas are rare benign vascular tumors,
      infrequent in pediatric patients. Clinical symptoms vary according to the age of
      presentation, tumor size, location, and concomitant syringomyelia. This is the
      second reported case of hemangioblastoma presenting with acute hydrocephalus.
      CASE PRESENTATION: A 3-month-old infant with acute hydrocephalus was asymptomatic
      after a ventriculoperitoneal shunt was placed. She returned 3 months later with
      irritability, acute paraplegia, and respiratory distress. Magnetic resonance
      imaging (MRI) showed an intramedullary T8-T9 tumor with syringomyelia. She
      underwent surgical resection with good results during the 6-month follow-up.
      CONCLUSION: Intramedullary tumors may present as hydrocephalus and other
      nonspecific symptoms, with invariably delayed diagnosis in children, but must be
      considered in suspicious cases.

PMID- 28444461
TI  - Tethered cord release after fetal surgery.

PMID- 28444462
TI  - Compartment Pressure Monitoring After Thyroid Surgery: A Possible Method to
      Detect a Rebleeding.
AB  - BACKGROUND: Postoperative rebleeding after thyroid surgery is a rare but a
      serious complication. The aim of this study was to ascertain the extent to which
      postoperative pressure could be used as detector for rebleeding after thyroid
      surgery. METHODS: Thirty-two patients with thyroidectomy or hemithyroidectomy
      were considered prospectively. In the course of surgery, a pressure microsensor
      (3PN Probe Spiegelberg) was implanted into the postoperative cavity and data were
      collected for special activities and stress situations over the first 48 h
      postoperatively. Additional endpoint was the influence of drains on the
      determined values. RESULTS: The overall mean pressure (MP) at rest on both
      postoperative days for all patients with and without drain was 0.36 +/- 2.84 mmHg
      (range -6.7 to 6.7). The MP in all activity and stress situations on the first
      day was with 0.23 +/- 3.71 mmHg, and on the second day, the MP was 1.33 +/- 4.50.
      92.13% of our values were below 7 mmHg. One patient had a hemorrhage. The
      pressure increases continuously up to 36 mmHg, before the patient was transferred
      to the operating theater. CONCLUSIONS: This is the first pilot study to consider
      continuous pressure measurement to be a potential tool for early detection of a
      postoperative rebleeding in thyroid surgery. In the strictest sense,
      postoperative intra-cervical pressure at rest ranges from subatmospheric to 7
      mmHg. The elevation of pressure in case of a rebleeding up to 36 mmHg differs
      dramatically from normal postoperative pressure. The collected data will warrant
      further validation to be able to recommend threshold values for an early
      treatment decisions in rebleeding.

PMID- 28444463
TI  - Cost-Effectiveness of Craniotomy for Epidural Hematomas at a Major Government
      Hospital in Cambodia.
AB  - BACKGROUND: Epidural hematoma (EDH) is a common and potentially deadly occurrence
      following a severe traumatic brain injury. Our aim was to determine whether
      craniotomy is cost-effective when indicated for the treatment of EDH when a
      trained neurosurgeon is available. METHODS: A decision tree was used to model the
      cost-effectiveness of craniotomy available versus craniotomy unavailable for the
      management of traumatic EDH from a Cambodian societal and provider perspective.
      Costs and effectiveness parameters were obtained from patient data at a large
      government hospital in Cambodia. Outcomes were measured in quality-adjusted life
      years (QALYs). Incremental cost per QALY and budget impact were calculated for
      each intervention at a willingness-to-pay (WTP) threshold of $9787.80/QALY (3*
      GDP per capita PPP). The time horizon reflected full life span, and costs and
      QALYs were discounted at 3%. Sensitivity analysis was also conducted. RESULTS:
      Compared to craniotomy unavailable for EDH ($945.80; 11.78 QALYs), craniotomy
      available came at a higher cost and greater effectiveness ($1520.73; 12.78
      QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of $574.93.
      One-way analysis demonstrated that craniotomy unavailable became more cost
      effective than craniotomy available when the percent chance of having a GOS of 4
      or 5 was 60% for patients with an EDH where craniotomy was indicated but not
      performed. Probabilistic sensitivity analysis revealed that craniotomy available
      was more cost-effective than conservative management in 84.4% of simulations at
      the WTP threshold. CONCLUSIONS: Craniotomy is a cost-effective treatment for
      patients with a traumatic EDH who meet criteria for operation when trained
      neurosurgeons are available onsite.

PMID- 28444464
TI  - Effectiveness of Antibiotic Prophylaxis in Non-emergency Cholecystectomy Using
      Data from a Population-Based Cohort Study.
AB  - BACKGROUND: There is a variation in the administration of antibiotics prophylaxis
      to reduce the perceived risk of SSI in patients undergoing non-emergency
      cholecystectomy. The aim of this study was to determine the effectiveness of
      antibiotic prophylaxis following non-emergency cholecystectomy to prevent 30-day
      superficial surgical site infections (SSIs) using non-selected, nationally
      collected, prospective data. METHODS: Data were extracted from the CholeS study,
      which examined and independently validated the outcomes on consecutive patients
      following non-emergency cholecystectomy across 166 hospitals in the UK and
      Ireland. Patients who received antibiotic prophylaxis were exact matched to those
      who did not on variables associated with antibiotic prophylaxis. The primary
      outcome of interest was superficial SSI, and secondary outcomes included deep
      SSI, readmissions, complications and re-interventions within 30 days. RESULTS:
      Out of a total of 7327 patients included in the study, 4468 (61%) received
      antibiotic prophylaxis. These were matched to patients who did not receive
      antibiotic prophylaxis on a range of demographic and surgical factors, leaving
      1269 pairs of patients for analysis. Within this cohort, patients receiving
      antibiotic prophylaxis had significantly lower rates of superficial SSI (0.7% vs.
      2.3%, p = 0.001) and all-cause complications (5.8 vs. 8.0%, p = 0.031), but
      similar rates of deep SSI (1.0 vs. 1.4%, p = 0.473), readmissions (5.2 vs. 6.2%,
      p = 0.302) and re-interventions (2.6 vs. 3.7%, p = 0.093). The number needed to
      treat to prevent one superficial SSI was 45 (95% confidence interval 24-662).
      CONCLUSIONS: Antibiotics appear effective at reducing SSI after non-emergency
      cholecystectomy. However, due to the high number needed to treat it is unclear
      whether they provide a worthwhile clinical benefit to patients.

PMID- 28444465
TI  - Rhythmic pupillary change in Cheyne-Stokes respiration.

PMID- 28444466
TI  - Sporadic Creutzfeldt-Jakob disease presenting with isolated progressive non
      fluent aphasia in a young woman.

PMID- 28444467
TI  - The role of perspective in discriminating between social and non-social
      intentions from reach-to-grasp kinematics.
AB  - Making correct inferences regarding social and individual intentions may be
      crucial for successful interactions, especially when we are required to
      discriminate between cooperative and competitive behaviors. The results of
      previous studies indicate that reach-to-grasp kinematic parameters may be used to
      infer the social or individual outcome of a movement. However, the majority of
      the studies investigated this ability by presenting reach-to-grasp movements from
      a third-person perspective only. The aim of the present study was to assess
      whether the ability to recognize the intent associated to a reach-to-grasp
      movement varies as a function of perspective by manipulating the perspective of
      observation (second- and third-perspective) within participants. To this end, we
      presented participants with video clips of models performing a reach-to-grasp
      movement with different intents. The video clips were recorded both from a
      lateral view (third-person perspective) and from a frontal view (second-person
      perspective). After viewing the clips, in two subsequent tasks participants were
      asked to distinguish between social and non-social intentions by observing the
      initial phase of the same action recorded from the two different views. Results
      showed that, when a fast-speed movement was presented from a lateral view,
      participants were able to predict its social intention. In contrast, when the
      same movement was observed from a frontal view, performance was impaired. These
      results indicate that the ability to detect social intentions from motor cues can
      be biased by the visual perspective of the observer, specifically for fast-speed
      movements.

PMID- 28444469
TI  - Modelling the UNAIDS 90-90-90 treatment cascade for gay, bisexual and other men
      who have sex with men in South Africa: using the findings of a data triangulation
      process to map a way forward.
AB  - A data triangulation exercise was carried out between 2013 and 2015 to assess the
      HIV epidemic and response among gay, bisexual and other men who have sex with men
      (GBMSM) in South Africa. We used the findings to assess progress in achieving the
      UNAIDS 90-90-90 goals for GBMSM in the country. Three scenarios were developed
      using different GBMSM population factors (2.0, 3.5 and 5.0% of males aged >=15)
      to estimate the population size, HIV prevalence of 13.2-49.5%, and 68% of GBMSM
      knowing their status. Due to data gaps, general population data were used as
      estimates of GBMSM on antiretroviral therapy (ART) and virologically suppressed
      (25.7 and 84.0%, respectively). The biggest gap is access to ART. To address the
      data gap we recommend developing data collection tools, indicators, and further
      quantification of HIV cascades. Targeted testing, linkage to services and scaled
      up prevention interventions (including pre-exposure prophylaxis) are also
      required.

PMID- 28444468
TI  - A new statistical model for analyzing rating scale data pertaining to word
      meaning.
AB  - The concrete-abstract categorization scheme has guided several research programs.
      A popular way to classify words into one of these categories is to calculate a
      word's mean value in a Concreteness or Imageability rating scale. However, this
      procedure has several limitations. For instance, results can be highly distorted
      by outliers, ascribe differences among words when none may exist, and neglect
      rating trends in participants. We suggest using an alternative procedure to
      analyze rating scale data called median polish analysis (MPA). MPA is tolerant to
      outliers and accounts for information in multiple dimensions, including trends
      among participants. MPA performance can be readily evaluated using an effect size
      measure called analog R 2 and be integrated with bootstrap 95% confidence
      intervals, which can prevent assigning inexistent differences among words. To
      compare these analysis procedures, we asked 80 participants to rate a set of
      nouns and verbs using four different rating scales: Action, Concreteness,
      Imageability, and Multisensory. We analyzed the data using both two-way and three
      way MPA models. We also calculated 95% CIs for the two-way models. Categorizing
      words with the Action scale revealed a continuum of word meaning for both nouns
      and verbs. The remaining scales produced dichotomous or stratified results for
      nouns, and continuous results for verbs. While the sample mean analysis generated
      continua irrespective of the rating scale, MPA differentiated among dichotomies
      and continua. We conclude that MPA allowed us to better classify words by
      discarding outliers, focusing on main trends, and considering the differences in
      rating criteria among participants.

PMID- 28444470
TI  - Sexual Orientation Differences in Health and Wellbeing Among Women Living with
      HIV in Canada: Findings from a National Cohort Study.
AB  - Sexual orientation differences in health and wellbeing among women living with
      HIV (WLH) are underexplored. Limited research available, however, suggests that
      sexual minority WLH may experience barriers to HIV care. Cross-sectional baseline
      data was analyzed from a Canadian cohort study with WLH (sexual minority women
      [SMW]: n = 180; heterosexual women: n = 1240). SMW (median age 38 years, IQR 13)
      included bisexual (58.9%), lesbian (17.8%) and other sexualities (23.3%). In
      multivariable analyses adjusting for age, poverty, education, and ethnicity, SMW
      identity was associated with increased odds of: clinical (80% vs. 100%
      antiretroviral adherence), intrapersonal (previous/current injection drug use
      [IDU] vs. no IDU history, depression, lower resilience), interpersonal (childhood
      abuse, sex work, adulthood abuse), and structural (HIV support services barriers,
      unstable housing, racial discrimination, gender discrimination) factors in
      comparison with heterosexual identity. Sexual minority WLH experience social and
      health disparities relative to heterosexual WLH, highlighting the need for
      interventions to promote health equity.

PMID- 28444471
TI  - The clinical experience and efficacy of radiofrequency device for wrinkle
      treatment.

PMID- 28444472
TI  - The Effect of Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibitors on
      Cardiometabolic Profile; Beyond the Hypoglycaemic Action.
AB  - Type 2 diabetes mellitus (T2DM) has growing prevalence worldwide and major
      clinical implications, chiefly cardiovascular (CV) and renal disease burden.
      Sodium-glucose co-transporter (SGLT)-2 inhibitors are a new drug class in the
      management of T2DM with a mechanism of action independent of insulin. In addition
      to their hypoglycaemic effect, SGLT-2 inhibitors appear to have haemodynamic and
      nephroprotective effects. Studies have consistently showed a modest but
      significant blood pressure (BP) reduction. Metabolic benefits are also attributed
      to SGLT-2 inhibitors with a modest but consistent body weight decrease recorded
      along with improvements in lipid profile and uric acid levels. Remarkable
      findings of significant cardioprotective effects came from the recent EMPA-REG
      study with a particular focus on heart failure. In the kidney, SGLT-2 inhibitors
      reduce hyperfiltration, a precipitant of diabetic nephropathy.

PMID- 28444473
TI  - Contrasting effects of engineered carbon nanotubes on plants: a review.
AB  - Rapid surge of interest for carbon nanotube (CNT) in the last decade has made it
      an imperative member of nanomaterial family. Because of the distinctive
      physicochemical properties, CNTs are widely used in a number of scientific
      applications including plant sciences. This review mainly describes the role of
      CNT in plant sciences. Contradictory effects of CNT on plants physiology are
      reported. CNT can act as plant growth inducer causing enhanced plant dry biomass
      and root/shoot lengths. At the same time, CNT can cause negative effects on
      plants by forming reactive oxygen species in plant tissues, consequently leading
      to cell death. Enhanced seed germination with CNT is related to the water uptake
      process. CNT can be positioned as micro-tubes inside the plant body to enhance
      the water uptake efficiency. Due to its ability to act as a slow-release
      fertilizer and plant growth promoter, CNT is transpiring as a novel nano-carbon
      fertilizer in the field of agricultural sciences. On the other hand, accumulation
      of CNT in soil can cause deleterious effects on soil microbial diversity,
      composition and population. It can further modify the balance between plant-toxic
      metals in soil, thereby enhancing the translocation of heavy metal(loids) into
      the plant system. The research gaps that need careful attention have been
      identified in this review.

PMID- 28444474
TI  - Compost and sulfur affect the mobilization and phyto-availability of Cd and Ni to
      sorghum and barnyard grass in a spiked fluvial soil.
AB  - Soil reclamation via additives can cause contradictory effects on the
      mobilization of toxic elements in soils under dry and wet conditions. Therefore,
      our aim was to investigate the impact of compost and sulfur in two rates (1.25
      and 2.5%) on fractionation, mobilization, and phyto-availability of cadmium (Cd)
      and nickel (Ni) to sorghum (dry soil) and barnyard grass (wet soil) in a fluvial
      soil spiked with 25 mg Cd or 200 mg Ni/kg soil. Compost decreased the solubility
      and mobilization of Cd (especially in dry soil) and Ni (in both soils). Sulfur
      increased the solubility of Cd (31% in dry soil-49% in wet soil) and Ni (4.6% in
      wet soil-8.7% in dry soil). Sulfur altered the carbonate fraction of Cd to the
      soluble fraction and the residual fraction of Cd and Ni to the non-residual
      fraction. Compost decreased Cd and increased Ni in sorghum, but enhanced Cd and
      degraded Ni in grass. Sulfur increased Cd and Ni in both plants, and the
      increasing rate of Cd was higher in grass than in sorghum, while Ni was higher in
      sorghum than in grass. These results suggest that compost can be used as an
      immobilizing agent for Cd in the dry soil and Ni in the wet soil; however, it
      might be used as mobilizing agent for Cd in the wet soil and Ni in the dry soil.
      Sulfur (with rate 2.5%) can be used for enhancing the phyto-extraction of Cd and
      Ni (especially Cd) from contaminated alkaline soils.

PMID- 28444475
TI  - Vertebral abnormality without spine-curvature deformity on prenatal
      ultrasonography: sonographic findings and postnatal radiographic correlations.
AB  - PURPOSE: To evaluate prenatal US features and postnatal radiographic findings of
      fetuses with a sonographically detected vertebral abnormality (VA) without spine
      curvature deformity (SCD). METHODS: Twenty-six fetuses showing a VA without SCD
      on prenatal US at our ultrasound center for a 5-year period were retrospectively
      identified and evaluated for sonographic data and coexisting anomalies. Medical
      records and postnatal radiographs of all 16 live births were reviewed. RESULTS:
      Coexisting major anomalies were suspected prenatally in 8/26 fetuses (30.8%).
      Sonographic abnormalities were noted in the vertebral body in 27/31 (87.1%) and
      in the posterior element in 4/31 (12.9%). US features were absent (n = 2) or
      small vertebral body echo (n = 21), two separate vertebral body echoes (n = 4),
      or smaller or lobulated posterior arch echoes (n = 4). Among 16 live-born
      neonates, postnatal radiographs revealed a vertebral abnormality in 20 (95.2%) of
      21 prenatally detected VA without SCD. The abnormalities were vertebral body
      hypoplasia (18/19) with an incomplete sagittal cleft, asymmetric/unilateral
      hypoplasia, or hypoplasia with a complete sagittal cleft; or abnormalities in the
      spinous process (2/2). CONCLUSIONS: Most fetuses with prenatally detected VA
      without SCD had hypoplastic vertebrae on postnatal radiographs. Prenatal
      recognition of VA without SCD can lead to an early postnatal diagnosis of a
      vertebral abnormality and guidance for follow-up.

PMID- 28444476
TI  - Assessing the Dim Light Melatonin Onset in Adults with Autism Spectrum Disorder
      and No Comorbid Intellectual Disability.
AB  - This study assessed melatonin levels and the dim light melatonin onset (DLMO) in
      adults with Autism Spectrum Disorder (ASD) and also investigated the
      relationships between melatonin and objectively measured sleep parameters.
      Sixteen adults with ASD (ASD-Only), 12 adults with ASD medicated for comorbid
      diagnoses of anxiety and/or depression (ASD-Med) and 32 controls participated in
      the study. Although, the timing of the DLMO did not differ between the two
      groups, advances and delays of the melatonin rhythm were observed in individual
      profiles. Overall mean melatonin levels were lower in the ASD-Med group compared
      to the two other groups. Lastly, greater increases in melatonin in the hour prior
      to sleep were associated with greater sleep efficiency in the ASD groups.

PMID- 28444477
TI  - Ethical conflicts in the treatment of fasting Muslim patients with diabetes
      during Ramadan.
AB  - BACKGROUND: For an effective treatment of patients, quality-assured safe
      implementation of drug therapy is indispensable. Fasting during Ramadan, an
      essential religious practice for Muslims, affects Muslim diabetics' drug use in a
      number of different ways. OBJECTIVES: Ethical problems arising from fasting
      during the month of Ramadan for practicing Muslim patients are being discussed on
      the basis of extant research literature. Relevant conflicts of interest
      originating in this situation are being analysed from an ethical perspective.
      MATERIAL AND METHODS: A number of databases have been searched systematically in
      view of the stated objectives to identify relevant studies. Starting point for
      this review are the following questions: What information is available regarding
      the fasting behaviour of Muslim diabetics during Ramadan? What kind of ethical
      problems can be identified in the context of this religious practice? RESULTS:
      The present review established a number of problems concerning medication
      adherence and drug use of practising Muslim diabetics during Ramadan, notably
      insufficient compliance, reduced frequency of consultations with their doctor,
      and inadequate, not sufficiently goal-oriented doctor-patient conversations about
      fasting. CONCLUSIONS: Deficiencies in medical as well as religious knowledge
      about fasting in Ramadan and a lack of sensitivity have been found among Muslim
      patients as well as among doctors. Compliance management and drug use in this
      area can be improved by effective, goal-oriented action plans and projects
      through which linguistic and cultural barriers can be addressed.

PMID- 28444478
TI  - The Association Between Geometry and Wall Stress in Emergently Repaired Abdominal
      Aortic Aneurysms.
AB  - Abdominal aortic aneurysm (AAA) is a prevalent cardiovascular disease
      characterized by the focal dilation of the aorta, which supplies blood to all the
      organs and tissues in the systemic circulation. With the AAA increasing in
      diameter over time, the risk of aneurysm rupture is generally associated with the
      size of the aneurysm. If diagnosed on time, intervention is recommended to
      prevent AAA rupture. The criterion to decide on surgical intervention is
      determined by measuring the maximum diameter of the aneurysm relative to the
      critical value of 5.5 cm. However, a more reliable approach could be based on
      understanding the biomechanical behavior of the aneurysmal wall. In addition,
      geometric features that are proven to be significant predictors of the AAA wall
      mechanics could be used as surrogates of the AAA biomechanical behavior and,
      subsequently, of the aneurysm's risk of rupture. The aim of this work is to
      identify those geometric indices that have a high correlation with AAA wall
      stress in the population of patients who received an emergent repair of their
      aneurysm. In-house segmentation and meshing algorithms were used to model 75 AAAs
      followed by estimation of the spatially distributed wall stress by performing
      finite element analysis. Fifty-two shape and size geometric indices were
      calculated for the same models using MATLAB scripting. Hypotheses testing were
      carried out to identify the indices significantly correlated with wall stress by
      constructing a Pearson's correlation coefficient matrix. The analyses revealed
      that 12 indices displayed high correlation with the wall stress, amongst which
      wall thickness and curvature-based indices exhibited the highest correlations.
      Stepwise regression analysis of these correlated indices indicated that wall
      stress can be predicted by the following four indices with an accuracy of 76%:
      maximum aneurysm diameter, aneurysm sac length, average wall thickness at the
      maximum diameter cross-section, and the median of the wall thickness variance.
      The primary outcome of this work emphasizes the use of global measures of size
      and wall thickness as geometric surrogates of wall stress for emergently repaired
      AAAs.

PMID- 28444479
TI  - The role of gender and labour status in immunosenescence of 65+ Polish
      population.
AB  - Women are living longer than men and it seems that one of the reasons could be
      better immune system of females. In Poland, contrary to many European countries,
      women retire earlier than men, namely at 60 and 65, respectively. We asked the
      question how the gender and labour status were interconnected with some
      immunological parameters included in the so called immune risk profile (IRP),
      such as CD4+/CD8+ ratio, percentage of CD8+CD28-, and NK, and the level of
      circulating cytokines. A total of 92 men and 100 women past the retirement age,
      namely 65-74 years old, still working or not, were examined. We have found
      statistically significant lower percentage of CD8+CD28- cells and non
      statistically significant higher CD4+/CD8+ ratio in women, whereas the percentage
      of NK was higher in men. Moreover, the percentage of CD8+CD28- cells was
      negatively correlated with the CD4+/CD8+ ratio and the concentration of IL8 was
      positively correlated with the concentration of IL10 both in men and women. In
      men, the level of IL10 was higher than in women. Altogether, we found that
      gender, but not labour status, influences immunosenescence of the examined
      population of 65-74 years old Polish people.

PMID- 28444481
TI  - Peer Victimization and Suicidal Thoughts and Behaviors in Depressed Adolescents.
AB  - Suicide is a leading cause of death among youth worldwide, and depressed
      adolescents are at a significantly elevated risk to report suicidal ideation,
      planning, and attempts. Peer victimization is a robust predictor of adolescent
      suicidal thoughts and behaviors (STBs), but little research has focused on why
      bullying leads to suicidal thoughts and behaviors. To address this empirical gap,
      we recruited 340 (246 female) depressed adolescents ages 13-19 (M = 15.59, SD =
      1.41) within 48 h of admission for acute psychiatric treatment. At the initial
      assessment, participants were administered clinical interviews characterizing
      psychopathology, nonsuicidal self-injury, and STBs (ideation, plans, and
      attempts). Further, they completed questionnaires assessing 3 forms of
      victimization (overt, relational, and reputational), recent risky behavior
      engagement, and psychiatric symptom severity. Controlling for internalizing
      symptoms and age, overt and reputational bullying were associated with more
      frequent past month suicide attempts, but not suicide ideation. Past month risky
      behavior engagement, but not NSSI, mediated the relation between victimization
      and attempts. However, sex differences revealed that this effect only held for
      males whereas bullying was directly associated with suicide attempts among
      females. In contrast, overt and relational bullying were non-linearly associated
      with suicide plans, and these relations were not mediated by risky behaviors or
      NSSI. Results highlight the complex network of factors that lead victimized
      adolescents to engage in STBs and may inform targeted suicide prevention and
      intervention programs.

PMID- 28444480
TI  - Model-based biotechnological potential analysis of Kluyveromyces marxianus
      central metabolism.
AB  - The non-conventional yeast Kluyveromyces marxianus is an emerging industrial
      producer for many biotechnological processes. Here, we show the application of a
      biomass-linked stoichiometric model of central metabolism that is experimentally
      validated, and mass and charge balanced for assessing the carbon conversion
      efficiency of wild type and modified K. marxianus. Pairs of substrates (lactose,
      glucose, inulin, xylose) and products (ethanol, acetate, lactate, glycerol, ethyl
      acetate, succinate, glutamate, phenylethanol and phenylalanine) are examined by
      various modelling and optimisation methods. Our model reveals the organism's
      potential for industrial application and metabolic engineering. Modelling results
      imply that the aeration regime can be used as a tool to optimise product yield
      and flux distribution in K. marxianus. Also rebalancing NADH and NADPH
      utilisation can be used to improve the efficiency of substrate conversion. Xylose
      is identified as a biotechnologically promising substrate for K. marxianus.

PMID- 28444482
TI  - Synthesis, pharmacological evaluation and molecular docking of pyranopyrazole
      linked 1,4-dihydropyridines as potent positive inotropes.
AB  - 1,4-Dihydropyridines are well-known calcium channel blockers, but variations in
      the substituents attached to the ring have resulted in their role reversal making
      them calcium channel activators in some cases. We describe the microwave-assisted
      eco-friendly approach for the synthesis of pyranopyrazole-1,4-dihydropyridines, a
      new class of 1,4-DHPs, under solvent-free conditions in good yield, and screen
      them for various in silico, in vitro and in vivo activities. The in vivo
      experimentation results show that the compounds possess positive inotropic
      effect, and the docking results validate their good binding with calcium
      channels. Compounds 7c, 7g and 7i appear to be the most effective positive
      inotropes, even at low doses, and bind with the calcium channels even more
      strongly than Bay K 8644, a well-known calcium channel activator. The
      chronotropic effect for the new compounds was also studied. The target and off
      target affinity profiling supported the in vivo results and revealed that the
      hybridized pyranopyrazole dihydropyridine scaffold has delivered new moderate
      hits, to be optimized, for the cytochrome P450 3A4 enzymes, opening avenues for
      combined pharmacological activity through standard structural modification.

PMID- 28444483
TI  - Exploring Racial, Gender, and Insurance Disparities in Patients with Osteoporotic
      Fractures.
AB  - The objective of this study is to examine racial, gender, and insurance
      disparities in hospital outcomes among patients diagnosed with osteoporotic
      fractures aged 55 years and older. A total of 36,153 patients were included in
      this study. The sample was constructed from de-identified patient-level data for
      2011 through 2014 from the Virginia Health Information (VHI) inpatient discharge
      database. Differences in mortality and 30-day readmission across race, gender,
      and insurance status were examined using logistic regression and generalized
      linear models for hospital charges and length of stay. Whites and Asians had a
      shorter stay than Blacks [5.2 days (95% confidence interval (CI) 5.1-5.3) and 5.0
      days (95% CI 4.7-5.2) vs. 5.6 days (95% CI 5.4-5.7)], while Hispanics had a
      significantly longer stay [6.0 days (95% CI 5.6-6.5)]. On average, total charges
      were the highest among Blacks [$37,916 (95% CI 36,784-39,083)]. All outcomes were
      poorer for men than women. Privately and publicly insured patients were more
      likely to be readmitted [odds ratio (OR) 1.6 (95% CI 1.0-2.6) and OR 2.0 (95% CI
      1.3-3.2)] and had a shorter stay than the uninsured [4.9 days (95% CI 4.8-5.0)
      and 5.2 days (95% CI 5.1-5.3) vs. 5.7 days (95% CI 5.4-6.0)], while privately
      insured patients had considerably lower total charges than those who were
      uninsured [$34,163 (95% CI 33,214-35,139) vs. $36,335 (95% CI 34,334-38,452)]. As
      evidenced from this study, there are racial, gender, and insurance disparities in
      health outcomes. These results and further exploration of these disparities could
      provide information necessary for strategies to improve these outcomes in at-risk
      patients diagnosed with osteoporotic fractures.

PMID- 28444484
TI  - Effectiveness of Drug Camps in Treatment of Substance Abuse in Thailand.
AB  - Various drug camps have been introduced in Thailand since the 2000s. This study
      explored the effects of drug camps in Thailand. Four provinces were selected to
      represent different region throughout Thailand. Assessments of 2679 drug users
      were carried out longitudinally, age ranging from 11 to 67 years old; assessments
      occurred before camp, after camps, and after a 1 year follow-up. Two hundred
      twenty-six camps organizers, community leaders, and lay people were selected as
      key informants. Twenty communities were observed prospectively and 400 lay people
      were studied. Self-administered questionnaires were utilized as well as interview
      guidelines and documents. It emerged that the effectiveness of drug camp was
      51.3% (intention-to-treat), whilst poly drug use increased significantly from
      before camp and 3 months after camp (repeated ANOVA p < 0.001) particularly among
      users aged 15 years old and over. Drug camps could be considered as an
      alternative measure for drug users; however, negative impacts should be
      considered.

PMID- 28444486
TI  - On the necessity of translational cognitive-neurotoxicological research in
      methamphetamine abuse and addiction.

PMID- 28444485
TI  - Evaluation of kinetic programs in various automated perimeters.
AB  - PURPOSE: Kinetic programs in four automated perimeters were evaluated and
      compared for their clinical usefulness using four simulated visual field (VF)
      patterns. METHODS: Using the results of conventional Goldmann manual kinetic
      perimetry (MKP), simulated fields with concentric contraction, a temporal
      residual island only, a small central island with a temporal island, and a ring
      scotoma were created. Four kinetic programs, Humphrey 750i Kinetic Test
      (Humphrey), OCULUS Twinfield 2 Kinetic Perimetry (OCULUS), OCTOPUS 900 Goldmann
      Kinetic Perimetry (OCTOPUS GKP), and Kowa AP-7000 Isopter (Kowa) were tested by
      the 4 simulated defect patterns using stimuli of V/4e, I/4e, I/3e, I/2e, and I/1e
      at speeds of 3 and 5 degrees /s. RESULTS: Except Humphrey, OCULUS, OCTOPUS GKP,
      and Kowa could obtain isopters nearly comparable to those of Goldmann MKP.
      However, their results were considerably influenced by the examiner's skill.
      Besides, Humphrey had restrictions on target presentation, and OCULUS and Kowa
      had problems in isopter drawing and in filling in the scotoma. OCTOPUS GKP was
      the only method that could correctly detect and depict all four defect patterns.
      It also had relatively shorter test durations among the three methods excluding
      Humphrey, which did not have a built-in function for test duration measurement.
      The perimeters' test ranges for the periphery were 90 degrees  for Humphrey,
      OCULUS, and OCTOPUS GKP, and 80 degrees  for Kowa. CONCLUSION: To assess kinetic
      fields with various defect patterns, OCTOPUS GKP seems to be the most useful
      method.

PMID- 28444487
TI  - The Anxiety Level of Caregivers of Neurological Patients with Dysphagia.
AB  - We aimed to investigate anxiety level of caregivers of neurological patients with
      dysphagia, and the relationship of patient-related factors to anxiety level of
      dysphagia caregivers. A total of 103 adult neurological patients with dysphagia
      (study group), 30 without dysphagia (control group), and their primary caregivers
      were included. Types of feeding, condition of dependency in eating and drinking,
      dysphagia duration, and history of previous dysphagia treatment were recorded for
      study group. In study group, the Turkish version of the Eating Assessment Tool-10
      (T-EAT-10) was used to determine dysphagia symptom severity. Penetration and
      aspiration severity was determined with the penetration-aspiration scale (PAS).
      The Spielberger State-Trait Anxiety Inventory (STAI) that has two subscales
      including state anxiety (S-STAI) and trait anxiety (T-STAI) was used to determine
      anxiety level of caregivers. There was no difference between groups in terms of
      age, gender, weight, and height. The mean S-STAI was 42.56 +/- 10.10 for the
      study group and 29.20 +/- 6.64 for the control group (p < 0.001). The mean T-STAI
      was 44.81 +/- 8.98 for the study group and 29.37 +/- 6.46 for the control group
      (p < 0.001). Significant correlation was detected between only T-STAI and history
      of previous dysphagia treatment (p = 0.01, r = 0.25). No correlation was found
      between STAI (in terms of both S-STAI and T-STAI) and T-EAT-10, PAS, types of
      feeding, condition of dependency in eating and drinking, dysphagia duration (p >
      0.05). Caregivers of neurological patients with dysphagia have greater anxiety
      level than caregivers of neurological patients without dysphagia.

PMID- 28444490
TI  - Association of Laparoscopic Surgeons of Great Britain and Ireland (ALSGBI),
      Annual Scientific Meeting, London, United Kingdom, 10-11 November 2016 :
      Scientific Papers.

PMID- 28444491
TI  - 24th International Congress of the European Association for Endoscopic Surgery
      (EAES) Amsterdam, The Netherlands, 15-18 June 2016 : Oral Presentations.

PMID- 28444488
TI  - Prophylactic Swallow Therapy for Patients with Head and Neck Cancer Undergoing
      Chemoradiotherapy: A Randomized Trial.
AB  - Evidence supporting prophylactic swallow exercises for patients with head and
      neck cancer (HNC) has not been universally demonstrated. This RCT examined diet
      level, feeding tube use, swallow function, and quality of life (QOL) of patients
      undergoing chemoradiotherapy who performed prophylactic swallowing exercises.
      Sixty HNC patients were randomized into exercise versus control groups.
      Swallowing, oromotor, toxicity, and QOL data were recorded (baseline, 3, 6, 12,
      24 months). Physiological swallow function was examined at baseline and 3 months.
      Swallow exercises were completed twice daily. Oral intake at 3 months was 10%
      better in the exercise group, which was not statistically significant (p = 0.49).
      Significant (p < 0.05) differences in secondary outcomes including oromotor
      function, pharyngeal impairment, oral pharyngeal swallow efficiency, and incisal
      opening were noted at early time points (3-6 months) in the exercise group.
      Possible positive early improvements in swallow function are associated with
      swallowing exercises, although these improvements are not significant longer
      term.

PMID- 28444489
TI  - Biodegradable Stents for Caustic Esophageal Strictures: Do They Work?
AB  - Biodegradable (BD) stents have been used for the management of various esophageal
      strictures (ES) but the experience of its use in caustic strictures is limited.
      The present study, aimed at evaluating efficacy of BD stents for the treatment of
      refractory caustic-induced ES, was a retrospective multi-center study conducted
      at three tertiary care centers in India wherein adult patients with refractory
      caustic induced strictures underwent placement of a BD stent. Patients were
      followed up for immediate complications and long term outcome. All 13 patients
      (39.3 +/- 15.1 years) underwent successful BD stent placement. Retrosternal chest
      pain occurred in 2 patients and stent migration in 1 (7.6%) patient. At 3 months,
      restenosis with recurrence of dysphagia was seen in nine (69.2%) patients, at 6
      months, 10 (77%) patients had dysphagia of whom three underwent surgery and the
      remaining seven patients required dilatations. At 1 year, one patient remained
      asymptomatic while nine had dysphagia. The requirement for dilatation was once in
      3 months in seven patients & once in a month in two patients. At 2 years, the
      requirement of dilatations was further reduced to once in 4-6 months in all
      patients. Over a 3 year follow up three (23%) patients had undergone surgery, one
      was free of symptoms while nine patients continued to be on periodic dilatation
      although the requirement had reduced to once in 4-6 months. Efficacy of BD stents
      in patients with caustic-induced ES is limited and the short term radial force
      applied by the currently available BD stents is inadequate to provide long term
      relief in such patients.

PMID- 28444492
TI  - Optimal radial force and size for palliation in gastroesophageal adenocarcinoma:
      a comparative analysis of current stent technology.
AB  - BACKGROUND: The optimal use of esophageal stents for malignant and benign
      esophageal strictures continues to be plagued with variability in pain tolerance,
      migration rates, and reflux-related symptoms. The aim of this study was to
      evaluate the differences in radial force exhibited by a variety of esophageal
      stents with respect to the patient's esophageal stricture. METHODS: Radial force
      testing was performed on eight stents manufactured by four different companies
      using a hydraulic press and a 5000 N force gage. Radial force was measured using
      three different tests: transverse compression, circumferential compression, and a
      three-point bending test. Esophageal stricture composition and diameters were
      measured to assess maximum diameter, length, and proximal esophageal diameter
      among 15 patients prior to stenting. RESULTS: There was a statistically
      significant difference in mean radial force for transverse compression tests at
      the middle (range 4.25-0.66 newtons/millimeter N/mm) and at the flange (range
      3.32-0.48 N/mm). There were also statistical differences in mean radial force for
      circumferential test (ranged from 1.19 to 10.50 N/mm, p < 0.001) and the three
      point bending test (range 0.08-0.28 N/mm, p < 0.001). In an evaluation of
      esophageal stricture diameters and lengths, the smallest median diameter of the
      stricture was 10 mm (range 5-16 mm) and the median proximal diameter normal
      esophagus was 25 mm (range 22-33 mm), which is currently outside of the range of
      stent diameters. CONCLUSIONS: Tested stents demonstrated significant differences
      in radial force, which provides further clarification of stent pain and
      intolerance in certain patients, with either benign or malignant disease.
      Similarly, current stent diameters do not successfully exclude the proximal
      esophagus, which can lead to obstructive-type symptoms. Awareness of radial
      force, esophageal stricture composition, and proximal esophageal diameter must be
      known and understood for optimal stent tolerance.

PMID- 28444493
TI  - Short-term outcomes of laparoscopy-assisted hybrid living donor hepatectomy: a
      comparison with the conventional open procedure.
AB  - BACKGROUND: Although minimally invasive living donor surgery has been
      increasingly accepted, its safety remains to be fully clarified in a large-scale
      study. This study evaluated the safety and effectiveness of our laparoscopy
      assisted hybrid living donor surgery (LAHDS) procedure with an upper median
      incision in comparison with conventional open donor hepatectomy (ODH). METHODS:
      From 2011 to 2016, 153 adult living donors [right lobe (RL) graft: 80 donors;
      left lobe (LL) graft: 73 donors] were enrolled and divided into LAHDS (n = 76)
      and ODH (n = 77) groups. Donor characteristics, surgical outcomes, and
      postoperative complications were compared between the 2 groups in each graft
      subgroup. Postoperative liver function tests (LFTs), inflammatory markers, pain
      parameters, incision-related symptoms, and recipient outcomes were compared
      between the 2 groups in all donors. RESULTS: In RL donors, operative blood loss
      was significantly lower in the LAHDS group than in the ODH group (201 vs. 313 g;
      p = 0.034). In LL donors, duration of surgery was significantly longer in the
      LAHDS group than in the ODH group (459 vs. 403 min; p = 0.034). The incidence of
      complications, length of hospital stay, and postoperative changes in both LFTs
      and inflammatory markers were comparable. The incidence of postoperative scar
      discomfort or tightness was significantly lower in the LAHDS group than in the
      ODH group (2.6 vs. 31.2%; p < 0.001), whereas postoperative pain parameters were
      comparable. The incidence of wound problems and abdominal wall numbness tended to
      be lower, but not significantly so, in the LAHDS group. CONCLUSIONS: This large
      consecutive case series demonstrates that our LAHDS procedure can be performed as
      safely as ODH, and it can improve quality of life without impaired donor and
      recipient outcomes.

PMID- 28444494
TI  - Imaging of pancreatic cystic lesions with confocal laser endomicroscopy: an ex
      vivo pilot study.
AB  - BACKGROUND: The differential diagnosis of pancreatic cystic lesions (PCLs) is an
      increasingly common clinical challenge. Confocal laser endomicroscopy (CLE) may
      differentiate PCLs by imaging of the cyst wall. However, clinical experience is
      still limited, and better image definition and characterization of the cyst wall
      in a spectrum of cysts are needed. This experimental study aimed to expose
      detailed imaging characteristics of PCLs by CLE. METHODS: Patients who underwent
      surgery of a PCL were enrolled. During surgery, intravenous fluorescein (2.5 ml
      of 10%) was injected just prior to the ligation of blood vessels supplying the
      pancreas. The freshly excised specimens were transected along the long axis to
      fully expose the luminal surface. A Gastroflex-UHD CLE probe (pCLE) was used
      manually to acquire images directly from the surface of cyst wall. The specimen
      subsequently underwent cross-sectional histology. All recorded data were analyzed
      by two investigators for predefined and original image findings of PCLs. RESULTS:
      Ten cases were recruited into the study. All patients underwent surgery because
      of a mucinous cyst with worrisome features or a symptomatic PCL. Imaging was
      successful in all patients and differently shaped papillary projections (PP) were
      visualized in eight patients. Pathological examination of those patients
      confirmed 6 cases with Intraductal Papillary Mucinous Neoplasm (IPMN) and 2 cases
      with Mucinous Cystic Neoplasm (MCN). In two patients with serous cystadenoma,
      typical vascular network was visualized in one patient, and microcystic
      structures in the other. Three of the IPMNs were malignant. The loss of papillary
      margin integrity and significant fragmentation together with irregularity was
      detected in malignant IPMNs by CLE. CONCLUSIONS: Pancreatic cyst epithelial wall
      can be visualized successfully by pCLE in ex vivo surgical specimens. Different
      papillary projections have been seen in all cases of IPMNs and MCNs. CLE has
      potential for identifying IPMN subtypes and for grading dysplasia.

PMID- 28444495
TI  - Establishing meaningful benchmarks: the development of a formative feedback tool
      for advanced laparoscopic suturing.
AB  - BACKGROUND: Time and accuracy are commonly used metrics to assess laparoscopic
      skills in a simulated environment. However, they do not provide trainees with
      meaningful information about how to improve their skills. The objective of this
      study was to provide preliminary validity evidence for the creation a formative
      feedback tool (FFT) for advanced laparoscopic suturing skills. METHODS:
      Videotapes of senior surgical residents (PGY3-5; SRs) and minimally invasive
      surgeons (MIS) performing 3 advanced laparoscopic suturing tasks were analyzed:
      needle handling (NH), suturing under tension (UT), and continuous suturing (CS).
      A FFT was created based on a grounded theory analysis of interviews with MIS
      surgeons about the key technical aspects of each task. The FFT was used to assess
      the videotaped performances of SRs and MIS surgeons by two blinded independent
      raters. RESULTS: The FFT is composed of three parts: NH contains 10 items, UT 18,
      and CS 20. Each item was classified according to seven key surgical principles:
      depth perception, safety, bimanual dexterity, exposure, tissue handling,
      instrument manipulation, and forward planning. The videotaped performance of SR
      and MIS surgeons was graded on a 3-point Likert scale ("does well," "needs some
      improvement," and "does poorly") and scores were calculated as a sum of the
      points. ICCs for all three tasks were high (NH 0.90, UT 0.87, and CS 0.90). FFT
      score correlated strongly with combined time and accuracy measurements for UT
      (0.82, p < 0.01) and CS (0.81, p < 0.01), and moderately for NH (0.65, p < 0.01).
      MIS surgeons performed significantly better than SRs on UT (p = 0.02) and CS (p =
      0.05), while scores on NH were similar (p = 0.57). CONCLUSIONS: A comprehensive
      tool for providing feedback about advanced laparoscopic suturing skills was
      developed. The FFT demonstrates evidence for validity as a measure of suturing
      skills and experience, and provides meaningful information to trainees about how
      to improve their skills and engage in more deliberate and efficient practice.

PMID- 28444496
TI  - Incidence of incisional hernia in the specimen extraction site for laparoscopic
      colorectal surgery: systematic review and meta-analysis.
AB  - INTRODUCTION: The incidence of incisional hernia(IH) may be affected by the
      choice of specimen extraction incision. The objective of this study was to
      perform a systematic review and meta-analysis comparing the incidence of IH after
      midline and off-midline incisions in patients undergoing laparoscopic colorectal
      surgery. METHODS: A systematic search was performed according to PRISMA
      guidelines to identify all comparative studies from January 1991-August 2016 on
      the incidence of IH after midline and off-midline(transverse or Pfannenstiel)
      incisions in patients undergoing laparoscopic colorectal surgery. Case series and
      studies reporting the IH after stoma site extraction, SILS, or NOTES were
      excluded. The MINORS instrument was used for quality assessment for observational
      studies. Weighted estimates were calculated using a random-effects model.
      RESULTS: A total of 17 articles were identified and included for meta-analysis,
      16 of which were observational studies and 1 was an RCT. The mean MINORS score
      for observational studies was 12.9 (SD 3.2, range 7-17). Sample sizes in the
      midline (mean 185, range 20-995) and off-midline(mean 184, range 20-903) groups
      were similar. Follow-up ranged from 17.3 to 42 months. The pooled incidence of IH
      was 10.6% (338/3177) in midline, 3.7% (48/1314) in transverse, and 0.9% (9/956)
      in Pfannenstiel incisions. IH was significantly higher in the midline compared to
      off-midline groups (weighted OR 4.1, 95% CI 2.0-8.3, I 2 = 79.7%, p for
      heterogeneity <0.001). Midline incisions were also at higher risk of IH versus
      transverse (weighted OR 3.0, 95% CI 1.4-6.7, I 2 = 72.7%, p for heterogeneity
      <0.001) and Pfannenstiel (weighted OR 8.6, 95% CI 3.0-24.6, I 2 = 43.5%, p for
      heterogeneity = 0.101) incisions. There was no publication bias according the
      funnel plot or statistically (Egger's p = 0.336). CONCLUSIONS: Midline incisions
      for specimen extraction in laparoscopic colorectal surgery are at significantly
      higher risk of IH compared to off-midline (transverse or Pfannenstiel) incisions,
      but these data are of poor quality and heterogeneous.

PMID- 28444497
TI  - Evaluation of crowd-sourced assessment of the critical view of safety in
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Faculty experts (FE) and crowd workers (CW) can assess technical
      skill, but assessment of operative technique has not been explored. We sought to
      evaluate if CW could be taught to assess completion of the critical view of
      safety (CVS) in laparoscopic cholecystectomy. METHODS: We prepared 160 blinded,
      surgical videos of laparoscopic cholecystectomy from public domain websites.
      Videos were edited to <=60 s, ending when a structure was cut/clipped. CW
      analyzed videos using Global Objective Assessment of Laparoscopic Skills (GOALS)
      and CVS criteria assessment tools after watching an instructional tutorial. Ten
      videos were randomly selected from each performance quartile based on GOALS. Five
      FE rated the 40 videos using GOALS and CVS. Linear mixed effects models derived
      average CW and FE ratings for GOALS and CVS for each video. Spearman correlation
      coefficients (SCC) were used to assess the degree of correlation between
      performance measures. Satisfactory completion of the CVS was defined as scoring
      an average CVS >= 5. Videos with an average GOALS >= 15 were considered top
      technical performers. RESULTS: A high degree of correlation was seen between all
      performance measures: CVS ratings between CW and FE, SCC 0.89 (p < 0.001); GOALS
      and CVS ratings SCC 0.77 (p < 0.001) for CW, and SCC 0.71 (p < 0.001) for FE.
      Sixteen videos were assigned top technical performer ratings by both CW and FE
      but the average CVS was inadequate (3.8 and 3.6, respectively), and the
      percentage of satisfactory CVS >= 5 was 12.5%. CONCLUSIONS: A high degree of
      correlation was found between CW and FE in assessment of the CVS. However, in
      this video analysis, high technical performers did not achieve a complete CVS in
      most cases. Educating CW to assess operative technique for the identification of
      low or average performers is feasible and may broaden the application of this
      assessment and feedback tool.

PMID- 28444498
TI  - Competition of Multiple Species in Advective Environments.
AB  - We study the effect of changes in flow speed on competition of an arbitrary
      number of species living in advective environments, such as streams and rivers.
      We begin with a spatial Lotka-Volterra model which is described by n reaction
      diffusion-advection equations with Danckwerts boundary conditions. Using the
      dominant eigenvalue [Formula: see text] of the diffusion-advection operator
      subject to boundary conditions, we reduce the model to a system of ordinary
      differential equations. We impose a "transitive arrangement" of the competitors
      in terms of their interspecific coefficients and growth rates, which means that
      in the absence of advection, we have the following situation: for all [Formula:
      see text], species i out-competes species j, while species j has higher intrinsic
      growth rate than species i. Changing advection speed in the original spatial
      model corresponds to changing the value of [Formula: see text] in the spatially
      implicit model. Considering the cases of the odd and even n separately, we obtain
      explicit intervals of the values of [Formula: see text] that allow all n species
      to be present in the habitat (coexistence interval). Stability of this
      equilibrium is shown for [Formula: see text].

PMID- 28444499
TI  - Hair Trace Element and Electrolyte Content in Women with Natural and In Vitro
      Fertilization-Induced Pregnancy.
AB  - The objective of the present study was to perform comparative analysis of hair
      trace element content in women with natural and in vitro fertilization (IVF)
      induced pregnancy. Hair trace element content in 33 women with IVF-induced
      pregnancy and 99 age- and body mass index-matched control pregnant women (natural
      pregnancy) was assessed using inductively coupled plasma mass spectrometry. The
      results demonstrated that IVF-pregnant women are characterized by significantly
      lower hair levels of Cu, Fe, Si, Zn, Ca, Mg, and Ba at p < 0.05 or lower.
      Comparison of the individual levels with the national reference values
      demonstrated higher incidence of Fe and Cu deficiency in IVF-pregnant women in
      comparison to that of the controls. IVF pregnancy was also associated with higher
      hair As levels (p < 0.05). Multiple regression analysis revealed a significant
      interrelation between IVF pregnancy and hair Cu, Fe, Si, and As content. Hair Cu
      levels were also influenced by vitamin/mineral supplementation and the number of
      pregnancies, whereas hair Zn content was dependent on prepregnancy anthropometric
      parameters. In turn, planning of pregnancy had a significant impact on Mg levels
      in scalp hair. Generally, the obtained data demonstrate an elevated risk of
      copper, iron, zinc, calcium, and magnesium deficiency and arsenic overload in
      women with IVF-induced pregnancy. The obtained data indicate the necessity of
      regular monitoring of micronutrient status in IVF-pregnant women in order to
      prevent potential deleterious effects of altered mineral homeostasis.

PMID- 28444500
TI  - Metastatic Follicular Thyroid Carcinoma and the Primary Thyroid Gross
      Examination: Institutional Review of Cases from 1990 to 2015.
AB  - The diagnosis of follicular-patterned carcinomas, including follicular thyroid
      carcinoma, oncocytic (Hurthle cell) carcinoma, and the encapsulated follicular
      variant of papillary thyroid carcinoma, requires evidence of capsular and/or
      vascular invasion. With minimally invasive carcinomas classified often within
      less than a millimeter of tissue segregating them from adenomas and non-invasive
      follicular thyroid neoplasms with papillary-like nuclear features, opinions vary
      internationally over how much of the capsule to submit in order to deem it well
      enough represented, considering that even if grossly entirely submitted in
      microcassettes, without leveling through each tissue block, the capsule is truly
      never entirely examined microscopically. Here, we retrospectively examine
      submission practices and outcomes at a single, high-volume institution over a 25
      year period. Our results indicate that the vast majority of lesions with poor
      outcomes are those with wide invasion, and tumors lacking gross evidence of
      capsular perturbation rarely lead to recurrence or metastasis, an unsurprising
      result that should prompt re-evaluation of our grossing methods and approach to
      follicular-patterned tumors in a time of cost restraint, molecular diagnostics,
      and low biological potential of encapsulated, circumscribed neoplasia of the
      thyroid.

PMID- 28444501
TI  - Validation of numerical simulation methods in aortic arch using 4D Flow MRI.
AB  - Computational fluid dynamics (CFD) are the gold standard in studying blood flow
      dynamics. However, CFD results are dependent on the boundary conditions and the
      computation model. The purpose of this study was to validate CFD methods using
      comparison with actual measurements of the blood flow vector obtained with four
      dimensional (4D) flow magnetic resonance imaging (MRI). 4D Flow MRI was performed
      on a healthy adult and a child with double-aortic arch. The aortic lumen was
      segmented to visualize the blood flow. The CFD analyses were performed for the
      same geometries based on three turbulent models: laminar, large eddy simulation
      (LES), and the renormalization group k-epsilon model (RNG k-epsilon). The flow
      velocity vector components, namely the wall shear stress (WSS) and flow energy
      loss (EL), of the MRI and CFD results were compared. The flow rate of the MRI
      results was underestimated in small vessels, including the neck vessels. Spiral
      flow in the ascending aorta caused by the left ventricular twist was observed by
      MRI. Secondary flow distal to the aortic arch was well realized in both CFD and
      MRI. The average correlation coefficients of the velocity vector components of
      MRI and CFD for the child were the highest for the RNG k-epsilon model (0.530 in
      ascending aorta, 0.768 in the aortic arch, 0.584 in the descending aorta). The
      WSS and EL values of MRI were less than half of those of CFD, but the WSS
      distribution patterns were quite similar. The WSS and EL estimates were higher in
      RNG k-epsilon and LES than in the laminar model because of eddy viscosity. The
      CFD computation realized accurate flow distal to the aortic arch, and the WSS
      distribution was well simulated compared to actual measurement using 4D Flow MRI.
      However, the helical flow was not simulated in the ascending aorta. The accuracy
      was enhanced by using the turbulence model, and the RNG k-epsilon model showed
      the highest correlation with 4D Flow MRI.

PMID- 28444502
TI  - Preliminary Study on the Role of TMEM39A Gene in Multiple Sclerosis.
AB  - Genome-wide association studies (GWAS) have identified hundreds of new potential
      genetic risk loci associated with numerous complex diseases such as multiple
      sclerosis (MS). Genes which have been discovered by GWAS are now the focus of
      numerous ongoing studies. The goal of this study was to confirm and understand
      the potential role of one of such genes-transmembrane protein 39A gene (TMEM39A)
      in multiple sclerosis.We showed the difference in TMEM39A messenger RNA (mRNA)
      expression between MS patients and controls (T 22;74 = 5.429; p = 0.0063). In our
      study, the lower mRNA expression of TMEM39A gene in patients did not correlate
      with a higher methylation level of the TMEM39A promoter. Moreover, a decreased
      level of TMEM39A mRNA was associated neither with rs1132200 nor with rs17281647.
      Additionally, we did not find an association between these two TMEM39A
      polymorphisms and the risk and progression of multiple sclerosis.Our
      investigation is the first which indicates that TMEM39A mRNA expression may be
      associated with the development and/or course of multiple sclerosis.

PMID- 28444503
TI  - Comparative evaluation of the algorithms for parametric mapping of the novel
      myocardial PET imaging agent 18F-FPTP.
AB  - OBJECTIVE: (18F-fluoropentyl)triphenylphosphonium salt (18F-FPTP) is a new
      promising myocardial PET imaging tracer. It shows high accumulation in
      cardiomyocytes and rapid clearance from liver. We performed compartmental
      analysis of 18F-FPTP PET images in rat and evaluated two linear analyses: linear
      least-squares (LLS) and a basis function method (BFM) for generating parametric
      images. The minimum dynamic scan duration for kinetic analysis was also
      investigated and computer simulation undertaken. METHODS: 18F-FPTP dynamic PET
      (18 min) and CT images were acquired from rats with myocardial infarction (MI) (n
      = 12). Regions of interest (ROIs) were on the left ventricle, normal myocardium,
      and MI region. Two-compartment (K 1 and k 2; 2C2P) and three-compartment (K 1-k
      3; 3C3P) models with irreversible uptake were compared for goodness-of-fit.
      Partial volume and spillover correction terms (V a and alpha = 1 - V a ) were
      also incorporated. LLS and BFM were applied to ROI- and voxel-based kinetic
      parameter estimations. Results were compared with the standard ROI-based
      nonlinear least-squares (NLS) results of the corresponding compartment model. A
      simulation explored statistical properties of the estimation methods. RESULTS:
      The 2C2P model was most suitable for describing 18F-FPTP kinetics. Average K 1, k
      2, and V a values were, respectively, 6.8 (ml/min/g), 1.1 (min-1), and 0.44 in
      normal myocardium and 1.4 (ml/min/g), 1.1 (min-1), and 0.32, in MI tissue. Ten
      minutes of data was sufficient for the estimation. LLS and BFM estimations
      correlated well with NLS values for the ROI level (K 1: y = 1.06x + 0.13, r 2  =
      0.96 and y = 1.13x + 0.08, r 2  = 0.97) and voxel level (K 1: y = 1.22x - 0.30, r
      2  = 0.90 and y = 1.26x + 0.00, r 2  = 0.92). Regional distribution of kinetic
      parametric images (alphaK 1, K 1, k 2, V a) was physiologically relevant. LLS and
      BFM showed more robust characteristics than NLS in the simulation. CONCLUSIONS:
      Fast kinetics and highly specific uptake of 18F-FPTP by myocardium enabled
      quantitative analysis with the 2C2P model using only the initial 10 min of data.
      LLS and BFM were feasible for estimating voxel-wise parameters. These two methods
      will be useful for quantitative evaluation of 18F-FPTP distribution in myocardium
      and in further studies with different conditions, disease models, and species.

PMID- 28444504
TI  - Correction of parallel transmission using concurrent RF and gradient field
      monitoring.
AB  - OBJECTIVES: The accuracy and precision of the parallel RF excitations are highly
      dependent on the spatial and temporal fidelity of the magnetic fields involved in
      spin excitation. The consistency between the nominal and effective fields is
      typically limited by the imperfections of the employed hardware existing both in
      the gradient system and the RF chain. In this work, we experimentally presented
      highly improved spatially tailored parallel excitations by turning the native
      hardware accuracy challenge into a measurement and control problem using an
      advanced field camera technology to fully correct parallel RF transmission
      experiment. MATERIALS AND METHODS: An array of NMR field probes is used to
      measure the multiple channel RF pulses and gradient waveforms recording the high
      power RF pulses simultaneously with low frequency gradient fields on equal time
      basis. The recorded waveforms were integrated in RF pulse design for gradient
      trajectory correction, time imperfection compensation and introduction of
      iterative RF pre-emphasis. RESULTS: Superior excitation accuracy was achieved.
      Two major applications were presented at 7 Tesla including multi-dimensional
      tailored RF pulses for spatially selective excitation and slice-selective spoke
      pulses for [Formula: see text] mitigation. CONCLUSION: Comprehensive field
      monitoring is a highly effective means of correcting for the field deviations
      during parallel transmit pulse design.

PMID- 28444505
TI  - Occupational heat stress assessment and protective strategies in the context of
      climate change.
AB  - Global warming will unquestionably increase the impact of heat on individuals who
      work in already hot workplaces in hot climate areas. The increasing prevalence of
      this environmental health risk requires the improvement of assessment methods
      linked to meteorological data. Such new methods will help to reveal the size of
      the problem and design appropriate interventions at individual, workplace and
      societal level. The evaluation of occupational heat stress requires measurement
      of four thermal climate factors (air temperature, humidity, air velocity and heat
      radiation); available weather station data may serve this purpose. However, the
      use of meteorological data for occupational heat stress assessment is limited
      because weather stations do not traditionally and directly measure some important
      climate factors, e.g. solar radiation. In addition, local workplace environmental
      conditions such as local heat sources, metabolic heat production within the human
      body, and clothing properties, all affect the exchange of heat between the body
      and the environment. A robust occupational heat stress index should properly
      address all these factors. This article reviews and highlights a number of
      selected heat stress indices, indicating their advantages and disadvantages in
      relation to meteorological data, local workplace environments, body heat
      production and the use of protective clothing. These heat stress and heat strain
      indices include Wet Bulb Globe Temperature, Discomfort Index, Predicted Heat
      Strain index, and Universal Thermal Climate Index. In some cases, individuals may
      be monitored for heat strain through physiological measurements and medical
      supervision prior to and during exposure. Relevant protective and preventive
      strategies for alleviating heat strain are also reviewed and proposed.

PMID- 28444506
TI  - Preoperative risk factors for prolonged postoperative ileus after colorectal
      resection.
AB  - PURPOSE: Prolonged postoperative ileus (PPOI) after colorectal resection
      significantly impacts patients' recovery and hospital stay. Because treatment
      options for PPOI are limited, it is necessary to focus on prevention strategies.
      The aim of this study is to investigate risk factors associated with PPOI in
      patients undergoing colorectal surgery. METHODS: Data from all consecutive
      patients who underwent colorectal resection in our department were
      retrospectively analyzed from a prospective database over a 9-month period. PPOI
      was defined as the necessity to insert a nasogastric tube in a patient who
      experienced nausea and two episodes of vomiting with absence of bowel function.
      Multivariable analysis was performed considering a prespecified list of 16
      potential preoperative risk factors. RESULTS: A total of 523 patients (mean age
      59 years; 52.2% males) were included, and 83 patients (15.9%) developed PPOI.
      Statistically significant independent predictors of PPOI were male sex (OR 2.07;
      P = 0.0034), open resection (OR 4.47; P < 0.0001), conversion to laparotomy (OR
      4.83; P = 0.0015), splenic flexure mobilization (OR 1.72; P = 0.063), and rectal
      resection (OR 2.72; P = 0.0047). Discriminative ability of this prediction model
      was 0.72. CONCLUSIONS: Therapeutic strategies aimed to prevent PPOI after
      colorectal resection should focus on patients with increased risk. Patients and
      medical staff can be informed of the higher PPOI risk, so that early treatment
      can be started.

PMID- 28444507
TI  - Heuristics and bias in rectal surgery.
AB  - PURPOSE: Deciding to defunction after anterior resection can be difficult,
      requiring cognitive tools or heuristics. From our previous work, increasing age
      and risk-taking propensity were identified as heuristic biases for surgeons in
      Australia and New Zealand (CSSANZ), and inversely proportional to the likelihood
      of creating defunctioning stomas. We aimed to assess these factors for colorectal
      surgeons in the British Isles, and identify other potential biases. METHODS: The
      Association of Coloproctology of Great Britain and Ireland (ACPGBI) was invited
      to complete an online survey. Questions included demographics, risk-taking
      propensity, sensitivity to professional criticism, self-perception of anastomotic
      leak rate and propensity for creating defunctioning stomas. Chi-squared testing
      was used to assess differences between ACPGBI and CSSANZ respondents. Multiple
      regression analysis identified independent surgeon predictors of stoma formation.
      RESULTS: One hundred fifty (19.2%) eligible members of the ACPGBI replied.
      Demographics between ACPGBI and CSSANZ groups were well-matched. Significantly
      more ACPGBI surgeons admitted to anastomotic leak in the last year (p < 0.001).
      ACPGBI surgeon age over 50 (p = 0.02), higher risk-taking propensity across
      several domains (p = 0.044), self-belief in a lower-than-average anastomotic leak
      rate (p = 0.02) and belief that the average risk of leak after anterior resection
      is 8% or lower (p = 0.007) were all independent predictors of less frequent stoma
      formation. Sensitivity to criticism from colleagues was not a predictor of stoma
      formation. CONCLUSIONS: Unrecognised surgeon factors including age, everyday risk
      taking, self-belief in surgical ability and lower probability bias of anastomotic
      leak appear to exert an effect on decision-making in rectal surgery.

PMID- 28444508
TI  - Study protocol on the role of intestinal microbiota in colorectal cancer
      treatment: a pathway to personalized medicine 2.0.
AB  - PURPOSE: Investigate in patients with metastatic and/or irresectable colorectal
      cancer treated with systemic treatment with capecitabine or TAS-102 whether: 1.
      Intestinal microbiota composition can act as a predictor for response. 2.
      Intestinal microbiota composition changes during systemic treatment and its
      relation to chemotoxicity. BACKGROUND: Gut microbiota and host determinants
      evolve in symbiotic and dependent relationships resulting in a personal
      ecosystem. In vitro studies showed prolonged and increased response to 5
      fluorouracil, a fluoropyrimidine, in the presence of a favorable microbiota
      composition. Capecitabine and TAS-102 are both fluoropyrimidines used for
      systemic treatment in colorectal cancer patients. METHODS: An explorative
      prospective multicenter cohort study in the Maastricht University Medical Centre+
      and Zuyderland Medical Centre will be performed in 66 patients. Before, during,
      and after three cycles of systemic treatment with capecitabine or TAS-102, fecal
      samples and questionnaires (concerning compliance and chemotoxicity) will be
      collected. The response will be measured by CT/MRI using RECIST-criteria. Fecal
      microbiota composition will be analyzed with 16S rRNA next-generation sequencing.
      The absolute bacterial abundance will be assessed with quantitative polymerase
      chain reaction. Multivariate analysis will be used for statistical analysis.
      CONCLUSIONS: We aim to detect a microbiota composition that predicts if patients
      with metastatic and/or irresectable colorectal cancer will respond to systemic
      treatment and/or experience zero to limited chemotoxicity. If we are able to
      identify a favorable microbiota composition, fecal microbiota transplantation
      might be the low-burden alternative to chemotherapy switch in the future.

PMID- 28444509
TI  - Impact of an Endoscopic Quality Improvement Program Focused on Adenoma Detection
      on Sessile Serrated Adenoma/Polyp Detection.
AB  - BACKGROUND: Sessile serrated adenomas/polyps (SSA/P) are an under-recognized
      disease with a unique malignant pathway. Improved endoscopic recognition and
      pathological interpretation is needed. AIMS: To determine whether an educational
      intervention that improved adenoma detection rate (ADR) could improve SSA/P
      detection rate after reclassification of previously termed "hyperplastic" polyps.
      METHODS: We reanalyzed data from a prospective randomized trial of an educational
      intervention aimed at increasing ADR. All hyperplastic polyps >=6 mm reported in
      a previously published study were rereviewed and reclassified using standardized
      criteria for serrated lesions. Detection rates of sessile serrated
      adenomas/polyps and other clinically relevant serrated polyps were calculated in
      the baseline and post-training phases of the original study. RESULTS: Of 263
      available for rereview, 33 (12.5%) were reclassified as SSA/P (N = 32) or
      traditional serrated adenoma (TSA) (N = 1). Reclassification was more common in
      the right colon (18 vs. 8%, p = 0.02). Baseline SSA/P detection rate was 0.7% in
      the untrained group and 1.3% in the trained group. Post-training, the SSA/P
      detection rate increased to 2.1 and 1.5%, respectively. The clinically relevant
      serrated polyp detection rate at baseline was 14.2% in the untrained group and
      11.3% in the trained group. After the educational intervention, the clinically
      relevant serrated polyp detection rates increased to 16.5 and 14.8% in the
      untrained and trained groups, respectively. The estimated odds of an endoscopist
      detecting either a SSA/P or other clinically relevant serrated polyp during
      colonoscopy increased by only 3% with the educational intervention (OR 1.03, 95%
      CI 0.61-1.74, p = 0.91). CONCLUSIONS: Pathological re-interpretation of larger
      serrated polyps resulted in the reclassification of 12.5% of lesions. Quality
      improvement methods focused on adenoma detection did not impact SSA/P detection,
      and thus specific methods for serrated polyp detection are needed.

PMID- 28444510
TI  - Starvation signals in yeast are integrated to coordinate metabolic reprogramming
      and stress response to ensure longevity.
AB  - Studies on replicative and chronological aging in Saccharomyces cerevisiae have
      greatly advanced our understanding of how longevity is regulated in all
      eukaryotes. Chronological lifespan (CLS) of yeast is defined as the age-dependent
      viability of non-dividing cell populations. A number of nutrient sensing and
      signal transduction pathways (mainly TOR and PKA) have been shown to regulate
      CLS, yet it is poorly understood how the starvation signals transduced via these
      pathways lead to CLS extension. Using reporters whose expressions are induced by
      glucose starvation, we have screened the majority of the 'signaling' mutants in
      the yeast genome and identified many genes that are necessary for stress
      response. Subsequent analyses of the 'signaling' mutants not only revealed novel
      regulators of CLS, such as the GSK-3 ortholog Mck1, but also demonstrated that
      starvation signals transmitted by SNF1/AMPK, PKC1 and those negatively regulated
      by TOR/PKA, including Rim15, Yak1 and Mck1 kinases, are integrated to enable
      metabolic reprogramming and the acquisition of stress resistance. Coordinated
      metabolic reprogramming ensures the accumulation of storage carbohydrates for
      quiescent cells to maintain viability. We provide new evidence that Yak1, Rim15
      and Mck1 kinases cooperate to activate H2O2-scanvenging activities, thus limiting
      the levels of ROS in cells entering quiescence. These findings support the recent
      advances in higher organisms that the flexibility of metabolic reprogramming and
      the balance between energetics and stress resistance are the unifying principles
      of lifespan extension. Future work to reveal how the metabolic switch and stress
      response is coordinated will help delineate the molecular mechanisms of aging in
      yeast and shed novel insight into aging/anti-aging principles in higher
      organisms.

PMID- 28444511
TI  - Scale-dependence in polychlorinated biphenyl (PCB) exposure effects on waterbird
      habitat occupancy.
AB  - Spatial scale is rarely considered in population-level assessments of contaminant
      impacts on wild animals; as a result misinterpretation of the relationship
      between contaminant exposure and population status may occur. We assessed the
      strength of expression of polychlorinated biphenyl (PCB) exposure effects at
      local vs. regional spatial scales on population status in five species of
      waterbirds, "bioaccumulators" often promoted as indicators of contaminant effects
      in aquatic ecosystems. Our focus was the upper Hudson River where PCBs occur at
      levels reported to have adverse impacts on wild birds. At the local scale,
      waterbird habitat occupancy was estimated from 220 repeat surveys made between
      2001 and 2010 along the same survey route divided into 25 contiguous river
      segments with markedly different PCB concentrations. At the regional scale,
      waterbird habitat occupancy in relation to proximity to the upper Hudson River
      was estimated across 1248 Breeding Bird Atlas survey blocks while controlling for
      region-wide variation in habitat availability. At the local scale, many
      associations of habitat and sampling covariates with species detection
      probabilities were evident but none, including PCB concentration, with habitat
      occupancy, extinction or colonization of a given river segment. At the regional
      scale, survey effort and habitat factors not related to PCB exposure were the
      most important drivers of waterbird occurrence although two species were more
      likely to occur farther from the contaminated river segment. Spatial scale
      clearly mediates expression of contaminant impacts on wild bird populations;
      large-scale, expert-generated databases provide an underused opportunity for
      better delineating the spatial scales at which population impacts occur and risk
      assessments should be performed.

PMID- 28444512
TI  - Endometrial cancer arising in adenomyosis versus endometrial cancer coexisting
      with adenomyosis: are these two different entities?
AB  - PURPOSE: While adenomyosis is one of the most common benign histologic findings
      in hysterectomy specimens of endometrial cancer, demographics of endometrial
      cancer arising in adenomyosis (EC-AIA) has not been well elucidated. The aim of
      this study is to evaluate histopathological findings and disease-free survival
      (DFS) of EC-AIA in comparison to endometrial cancer coexisting with adenomyosis
      (EC-A). METHODS: EC-AIA cases were identified via a systematic literature search
      (n = 46). EC-A cases were identified from a historical cohort that underwent
      hysterectomy-based surgical staging in two institutions (n = 350). Statistical
      comparisons of the two groups were based on univariate and multivariate analyses.
      RESULTS: The EC-AIA group was significantly older than the EC-A group (58.9
      versus 53.8, p = 0.002). As to tumor characteristics, 63.6% of EC-AIA cases
      reported tumor within the myometrium without endometrial extension. The EC-AIA
      group was significantly associated with more non-endometrioid histology (23.9
      versus 14.8%; p = 0.002) and deep myometrial tumor invasion (51.6 versus 19.4%; p
      < 0.001) than EC-A. Tumor grade, stage, and nodal metastasis risk were similar
      (all, p > 0.05). In a univariate analysis, the EC-AIA group had a significantly
      decreased DFS compared to EC-A (5-year rates, 72.2 versus 85.5%, p = 0.001).
      After controlling for age, histology, tumor grade, and stage, EC-AIA remained an
      independent prognostic factor associated with decreased DFS compared to EC-A
      (adjusted-hazard ratio 2.87, 95% confidence interval 1.44-5.70, p = 0.031).
      CONCLUSION: Our study demonstrated that EC-AIA has distinct tumor characteristics
      and a poorer survival outcome compared to EC-A. This suggests a benefit of
      recognition of this unique entity as an aggressive variant of endometrial cancer.

PMID- 28444513
TI  - In vitro fertilization when men, women, or both partners are positive for HIV: a
      case-control study.
AB  - PURPOSE: The aim of this study was to compare the outcomes of in vitro
      fertilization (IVF) for couples where one or both partners were positive for the
      human immunodeficiency virus (HIV) to matched control couples. METHODS: A matched
      case-control retrospective study was performed. Data for 104 couples where the
      woman was HIV-positive; for 90 couples where the man was HIV-positive; and for 33
      couples where both partners were HIV-positive were prospectively analyzed in
      comparison to matched controls treated in our center during the same period. The
      main outcomes were clinical pregnancy and live birth rates. RESULTS: For couples
      involving an HIV-positive man, clinical outcomes were comparable to controls and
      resulted in the birth of 18 healthy babies after 90 cycles. When the woman was
      affected, cycle cancelation, number of retrieved oocytes, and on-going clinical
      pregnancy rates per transfer were statistically reduced. Implantation rates were
      comparable to those of non-affected controls. Seven healthy babies for 104 cycles
      were obtained. For a couple in which both partners were HIV-positive, only one
      healthy birth occurred after 33 cycles. Pregnancy rates were systematically
      reduced though not significantly probably due to sample size. CONCLUSIONS: Our
      data suggest that IVF outcomes were similar to controls when men were HIV
      positive and remain acceptable when women were HIV-positive. IVF outcomes were
      severely reduced in our sero-concordant couples; however, many patients had
      severe HIV disease previously, and therefore, these results should be reassessed
      in patients treated early in their disease.

PMID- 28444514
TI  - Pelvic organ prolapse stage IV and cervical cancer FIGO IIa.

PMID- 28444515
TI  - Cataract Surgery in Patients with a Previous History of KAMRA Inlay Implantation:
      A Case Series.
AB  - INTRODUCTION: The visual outcome of cataract surgery in patients with a previous
      history of KAMRA inlay implantation is an emerging issue for which limited
      research exists. The purpose of this study is to describe postoperative visual
      outcomes in this patient population. METHODS: This is a case series with
      retrospective chart review. Seven patients underwent cataract surgery following
      KAMRA corneal inlay implantation. Visual acuity was assessed before and after
      cataract surgery. Keratometry was measured before and after KAMRA inlay
      implantation, and optical biometry was performed prior to cataract surgery.
      RESULTS: Postoperatively, uncorrected distance visual acuity (UDVA) was 20/20 in
      five (71%) patients and 20/40 or better in seven (100%) patients, corrected
      distance visual acuity (CDVA) was 20/20 or better in six (86%) patients and 20/25
      in seven (100%) patients, and uncorrected near visual acuity (UNVA) was J1 in
      four (57%) patients, J2 or better in six (86%) patients, and J3 or better in
      seven (100%) patients. There was no significant change in keratometry after KAMRA
      inlay implantation. Biometry calculations accurately predicted intraocular lens
      (IOL) power after cataract surgery. Surgeons did not report a significant change
      in the surgical technique of cataract surgery. CONCLUSION: Patients who undergo
      cataract surgery with a previous history of KAMRA inlay implantation have good
      visual outcomes. Furthermore, intraocular lens (IOL) calculations accurately
      predict power, and there appears to be no significant change in surgical
      technique.

PMID- 28444516
TI  - Trap-Nesting Hymenoptera and Their Network with Parasites in Recovered Riparian
      Forests Brazil.
AB  - Different aspects of human activities can cause environmental change that
      endanger species persistence, alter species distributions, and lead to changes in
      antagonistic and mutualistic interactions, whereas deforestation and flooding of
      riparian forest results in landscapes consisting of patchily distributed riparian
      forest fragments in a matrix of pastures, plantations, and urban areas.
      Therefore, we assessed the richness, abundance, and trophic interactions of trap
      nesting Hymenoptera and their parasites at four patches of restored riparian
      forest and at one reference natural fragment, of different sizes and ages,
      located at the Volta Grande Reservoir, in Minas Gerais and Sao Paulo states to
      answer the following questions: (1) Does the richness and abundance of cavity
      nesting bees and wasps differ in riparian forest fragments according to the
      seasonal periods? (2) Does the composition of cavity-nesting bees and wasps vary
      among restoration and reference sites and between climate seasons (wet and dry)?
      (3) How do the degrees of specialization of the parasites vary among the patches
      of forest? We recorded 12 species of wasps, eight of bees, and nine species of
      parasites. Areas with longer time since restoration (reference site) showed
      higher species richness. However, the abundance was higher in most recent areas.
      The composition of bee and wasp assembly has not significantly changed between
      the climate seasons, although it is different between sampling areas. The
      richness and abundance were higher in warmer and rainy periods. The rate of bee
      and wasp mortality was high. The degree of specialization of parasites varies
      among sampling units, and the network of host-parasite interaction has a modular
      configuration with generalists and specialists. We concluded that the restored
      areas with more complex habitat could provide better conditions for the
      reestablishment of ecological interactions among these insects, the local flora,
      and other invertebrates, which together contribute to the success of the restored
      environments.

PMID- 28444517
TI  - Intravascular large B-cell lymphoma as a cause of terminal acute respiratory
      distress syndrome: atypical presentation of a rare disease.

PMID- 28444518
TI  - Video-Based Approach to Engaging Parents into a Preventive Parenting Intervention
      for Divorcing Families: Results of a Randomized Controlled Trial.
AB  - The public health impact of evidence-based, preventive parenting interventions
      has been severely constrained by low rates of participation when interventions
      are delivered under natural conditions. It is critical that prevention scientists
      develop effective and feasible parent engagement methods. This study tested video
      based methods for engaging parents into an evidence-based program for divorcing
      parents. Three alternative versions of a video were created to test the
      incremental effectiveness of different theory-based engagement strategies based
      on social influence and health behavior models. A randomized controlled trial was
      conducted to compare the three experimental videos versus two control conditions,
      an information-only brochure and an information-only video. Participants were
      attendees at brief, court-mandated parent information programs (PIPs) for
      divorcing or never married, litigating parents. Of the 1123 eligible parents, 61%
      were female and 13% were never married to the child's other parent. Randomization
      to one of five conditions was conducted at the PIP class level, blocking on
      facilitator. All participants completed a 15-item, empirically validated risk
      index and an invitation form. Results of regression analyses indicated that the
      most streamlined version, the core principles video, significantly increased
      parents' interest in participating in the parenting intervention, enrollment
      during a follow-up call, and initiation (i.e., attending at least one session)
      compared to one or the other control conditions. Findings suggest that videos
      based on social influence and health behavior theories could provide an effective
      and feasible method for increasing parent engagement, which would help maximize
      the public health benefits of evidence-based parenting interventions.

PMID- 28444519
TI  - Intention to Enact and Enactment of Gatekeeper Behaviors for Suicide Prevention:
      an Application of the Theory of Planned Behavior.
AB  - Gatekeeper training for suicide prevention was evaluated on a college campus to
      examine the impact of training on gatekeeper enactment of behaviors in support of
      suicide prevention and identify predictors of enactment of gatekeeper behaviors.
      Trained gatekeepers (N = 216) displayed greater perceived knowledge and self
      efficacy for suicide prevention and reported higher rates of self-reported actual
      gatekeeper behaviors, including inquiring about suicidal ideation and referring
      for mental health treatment when they encountered someone in distress, compared
      to their untrained counterparts (N = 169). Consistent with the Theory of Planned
      Behavior, SEM results indicated that attitudes, self-efficacy, and perceived
      knowledge explained intentions to engage in gatekeeper behaviors, accounting for
      59% of the variance in intentions to inquire about suicidal ideation and
      supporting the role of attitudes and perceived behavioral control in intentions
      to act. These intentions explained self-reported actual gatekeeper behaviors
      among participants who encountered someone in distress, with each one-point
      increase in intention associated with nearly twice the likelihood of both
      inquiring about suicidal ideation and referring someone for mental health care.
      On the other hand, self-reported situational barriers were associated with a
      decreased likelihood of referral behavior, indicating the role of actual
      behavioral control over volitional actions. Findings support the value of
      gatekeeper training for promoting factors that influence the likelihood of action
      on behalf of suicide prevention.

PMID- 28444520
TI  - Elevational plant species richness patterns and their drivers across non
      endemics, endemics and growth forms in the Eastern Himalaya.
AB  - Despite decades of research, ecologists continue to debate how spatial patterns
      of species richness arise across elevational gradients on the Earth. The
      equivocal results of these studies could emanate from variations in study design,
      sampling effort and data analysis. In this study, we demonstrate that the
      richness patterns of 2,781 (2,197 non-endemic and 584 endemic) angiosperm species
      along an elevational gradient of 300-5,300 m in the Eastern Himalaya are hump
      shaped, spatial scale of extent (the proportion of elevational gradient studied)
      dependent and growth form specific. Endemics peaked at higher elevations than non
      endemics across all growth forms (trees, shrubs, climbers, and herbs). Richness
      patterns were influenced by the proportional representation of the largest
      physiognomic group (herbs). We show that with increasing spatial scale of extent,
      the richness patterns change from a monotonic to a hump-shaped pattern and
      richness maxima shift toward higher elevations across all growth forms. Our
      investigations revealed that the combination of ambient energy (air temperature,
      solar radiation, and potential evapo-transpiration) and water availability (soil
      water content and precipitation) were the main drivers of elevational plant
      species richness patterns in the Himalaya. This study highlights the importance
      of factoring in endemism, growth forms, and spatial scale when investigating
      elevational gradients of plant species distributions and advances our
      understanding of how macroecological patterns arise.

PMID- 28444521
TI  - Leprosy in Children.
AB  - PURPOSE OF REVIEW: This manuscript aims to review the cutting-edge developments
      regarding to the diagnosis, management, and prevention of leprosy in children.
      RECENT FINDINGS: Leprosy transmission still occurs continuously in some endemic
      areas in the world. Leprosy in children below 15 years old is a robust indicator
      of active source of infection in the community where they live. A special focus
      on children to reduce disabilities and reduce transmission is one of the core
      areas of interventions of the global leprosy strategy 2016-2020. Ongoing research
      is trying to develop better diagnostic tests and to advance chemoprophylaxis and
      immunoprophylaxis approaches. Early diagnosis in children can be hard because of
      the wide range of clinical aspects of the skin lesions and mainly due to the
      difficulty of performing the clinical peripheral nerve evaluation. We must
      maintain leprosy expertise and improve the health professionals training for
      leprosy diagnosis, since we still have a long journey to reach leprosy
      elimination.

PMID- 28444522
TI  - The movement-induced self-reference effect: enhancing memorability through
      movement toward the self.
AB  - Much evidence suggests that bodily actions affect cognitive states. In
      particular, pulling owned objects toward the self improves memory for those
      objects compared to memory for objects pushed away from the self. Experiments 1
      and 2 examined the effect of incidental joystick movement on static stimuli,
      hypothesizing that using the physical self (rather than a computer monitor) as a
      reference point would enhance memory for items categorized via a toward-the-self
      action but not toward-the-computer-monitor action. Experiment 3 examined whether
      movement toward an external representation of self, one's cellular phone, would
      enhance memory compared to the same movement toward an unfamiliar phone.
      Recognition memory was enhanced for both words and pictures evaluated during
      movements toward a representation of the self, regardless of whether the
      representation was a physical self or a disembodied self. Furthermore, movement
      toward the self enhanced memory, rather than movement away from the self
      depressing memory. These results suggest that self-referential processing can be
      induced by an approach motor action and impact episodic memory regardless of
      intention to learn, stimulus type, or motion of the stimuli. They also suggest
      that self-referential memory advantage can be disembodied.

PMID- 28444523
TI  - IOP measurement in silicone oil tamponade eyes by Corvis ST tonometer, Goldmann
      applanation tonometry and non-contact tonometry.
AB  - PURPOSE: To compare the postoperative intraocular pressure (IOP) of eyes
      following pars plana vitrectomy (PPV) combined with intravitreal silicone oil
      (SO) tamponade by Corneal Visualization Scheimpflug Technology (CST), Goldmann
      applanation tonometry (GAT) and non-contact tonometry (NCT). METHODS: Thirty
      eight participants who had undergone PPV combined with SO tamponade to treat
      vitreoretinal diseases were enrolled. Postoperative IOP measurements were
      obtained using CST, NCT and GAT. Inter-device agreement was assessed by Bland
      Altman analysis. The correlation coefficient was used to describe the potential
      postoperative factors affecting the postoperative IOP differences between each
      device. RESULTS: Bland-Altman analysis revealed the bias between CST and GAT,
      between CST and NCT, and between GAT and NCT to be -0.2, 2.1 and 2.4 mmHg,
      respectively. CST and GAT correlated well with each other. NCT values were lower
      than those of GAT and CST (all p < 0.05), whereas CST values did not differ from
      the GAT readings. Central corneal thickness, corneal biomechanical properties and
      age showed significant correlation with the differences of CST-NCT and GAT-NCT.
      CONCLUSIONS: In SO tamponade eyes, NCT obtains lower IOP than other tonometry
      techniques, and CST is highly consistent with GAT. CST offers an optional non
      contact method for measuring postoperative IOP in SO tamponade eyes.

PMID- 28444524
TI  - In vitro optical quality of monofocal aspheric toric intraocular lenses: effect
      of cylindrical power.
AB  - PURPOSE: To assess the in vitro optical quality of monofocal aspheric toric
      intraocular lenses (IOLs) as a function of the cylindrical power. METHODS: The in
      vitro optical quality of the AcrySof IQ Toric IOLs SN6AT2, SN6AT3, SN6AT4, SN6AT5
      and SN6AT6 (Alcon Laboratories Inc., Forth Worth, TX, USA) was assessed with an
      instrument conceived for measuring Zernike's coefficients at 3.0- and 5.0-mm
      apertures. As a reference, the aspheric monofocal lens AcrySof IQ Aspheric SN60WF
      (Alcon Laboratories Inc., Forth Worth, TX, USA) was also measured. The area of
      visibility and cut-off frequency were used to describe the modulation transfer
      function (MTF) of each lens; meanwhile, the light in the bucket and the diameter
      of a circular area centred on the point-spread function (PSF) peak that captures
      50% of the light energy were used to describe the PSF of each lens. Finally, an
      image simulation was computed from the Zernike values with reference purposes.
      RESULTS: Small differences were found on the metrics used for describing the MTF
      and PSF of the lenses at both tested apertures, but these were not statistically
      significant (p > 0.05). Furthermore, the image simulation showed that these
      differences would not have clinical relevance at all. CONCLUSIONS: The optical
      performance of the AcrySof IQ toric IOLs in terms of MTF and PSF is good and
      seems to be independent of the cylindrical power and similar to a non-toric
      aspheric lens.

PMID- 28444526
TI  - Endoluminal stapler prototype for rectal transection.

PMID- 28444525
TI  - Comparison of biometric measurements obtained by the Verion Image-Guided System
      versus the auto-refracto-keratometer.
AB  - PURPOSE: To compare the biometric measurements obtained from the Verion Image
      Guided System to those obtained by auto-refracto-keratometer in normal eyes.
      METHODS: This is a prospective, observational, comparative study conducted at the
      Asociacion para Evitar la Ceguera en Mexico I.A.P., Mexico. Three sets of
      keratometry measurements were obtained using the image-guided system to assess
      the coefficient of variation, the within-subject standard deviation and
      intraclass correlation coefficient (ICC). A paired Student t test was used to
      assess statistical significance between the Verion and the auto-refracto
      keratometer. A Pearson's correlation coefficient (r) was obtained for all
      measurements, and the level of agreement was verified using Bland-Altman plots.
      RESULTS: The right eyes of 73 patients were evaluated by each platform. The
      Verion coefficient of variation was 0.3% for the flat and steep keratometry, with
      the ICC being greater than 0.9 for all parameters measured. Paired t test showed
      statistically significant differences between groups (P = 0.0001). A good
      correlation was evidenced for keratometry values between platforms (r = 0.903, P
      = 0.0001 for K1, and r = 0.890, P = 0.0001). Bland-Altman plots showed a wide
      data spread for all variables. CONCLUSION: The image-guided system provided
      highly repeatable corneal power and keratometry measurements. However,
      significant differences were evidenced between the two platforms, and although
      values were highly correlated, they showed a wide data spread for all analysed
      variables; therefore, their interchangeable use for biometry assessment is not
      advisable.

PMID- 28444527
TI  - Endoscopic ultrasound-guided fine needle aspiration of extra-rectal lesions.

PMID- 28444528
TI  - Horizontal rectal transection using an endolinear stapler for laparoscopic low
      anterior resection.

PMID- 28444529
TI  - "We Deserve Better!": Perceptions of HIV Testing Campaigns Among Black and Latino
      MSM in New York City.
AB  - In 2014, Black/African-American and Hispanic/Latino men who have sex with men
      (BLMSM) comprised 64.1% of HIV diagnoses among MSM in the U.S. Routine HIV
      testing allows earlier diagnosis, linkage to care, and improved health outcomes.
      HIV testing campaigns may increase HIV awareness and testing behaviors, but
      perceptions of these campaigns by BLMSM have been understudied. We explored
      perceptions of HIV testing campaigns with BLMSM in New York City (NYC) to inform
      campaign strategies that target BLMSM for HIV testing. Using respondent-driven
      sampling methods, we conducted semi-structured interviews from 2011 to 2012 with
      BLMSM in NYC who participated in a larger HIV research study. Interview responses
      from 108 participants were examined for main themes using computer-assisted
      thematic analyses. The four main themes identified were that HIV testing
      campaigns should: (1) use non-stereotypical messages and images on the basis of
      race and sexuality, (2) use non-gay identified images, (3) be maximally inclusive
      and visible, and (4) raise risk perception of HIV. These findings can inform
      future campaigns for strengthening HIV testing among BLMSM in support of earlier
      diagnosis, linkage to care, and reduced disparities.

PMID- 28444530
TI  - "That's Kind of One of Our Jobs": Sexual Activity as a Form of Care Work Among
      Women with Sexual Difficulties.
AB  - Willing engagement in unwanted or undesired sexual activity, often associated
      with fulfilling a partner's needs or sustaining intimate relationships, is
      common. Acquiescence with undesired sexual activity can be conceptualized as
      sexual care work, that is, domestic "labor" that women undertake with the goal of
      caring for their partners' well-being. Drawing on interviews with 53 women with
      dyspareunia (pain experienced during intercourse) and low desire, the aim of this
      study was to examine how women with sexual difficulties engage in sexual care
      work, the implications of the inability to perform such work for gender identity,
      and the ways in which sexual care work may blur the lines between women's
      perceptions of coercion and consent. The women in this study engaged in sexual
      activity for a number of reasons, including the pursuit of intimacy, to care for
      their partner, and to fulfill their perceived sexual obligations. Sexual
      compliance was conceptualized as a form of work, similar to other forms of unpaid
      care work such as housework or childcare, which negatively affected women's
      gender identities when it could not be performed. For many women, sex was
      simultaneously wanted and unwanted, contributing to women's ambivalence regarding
      the meaning of consent. Further exploration of these issues may lead to a better
      understanding of how gender is achieved through normative sexuality.

PMID- 28444531
TI  - Multifaceted Sexual Desire and Hormonal Associations: Accounting for Social
      Location, Relationship Status, and Desire Target.
AB  - Sexual desire is typically measured as a unitary erotic phenomenon and is often
      assumed by biological and biomedical researchers, as well as the lay public, to
      be directly connected to physiological parameters like testosterone (T). In the
      present study, we empirically examined how conceptualizing sexual desire as
      multifaceted might clarify associations with T and contextual variables. To do
      so, we used the Sexual Desire Questionnaire (DESQ), which assesses multifaceted
      dyadic sexual desire, to explore how contextual variables such as social
      location, relationship status, and desire target (e.g., partner vs. stranger)
      might be meaningful for reports of sexual desire and associated hormonal
      correlations. We focused on women (N = 198), because sexual desire and
      testosterone are generally unlinked in healthy men. Participants imagined a
      partner or stranger while answering the 65 DESQ items and provided a saliva
      sample for hormone assay. Analyses showed that the DESQ factored differently for
      the current sample than in previous research, highlighting how sexual desire can
      be constructed differently across different populations. We also found that, for
      the Intimacy, Eroticism, and Partner Focus factors, mean scores were higher when
      the desire target was a partner relative to a stranger for participants in a
      relationship, but equally high between partner versus stranger target for single
      participants. DESQ items resolved into meaningful hormonal desire components,
      such that high endorsement of Fantasy Experience was linked to higher T, and
      higher cortisol was linked with lower endorsement of the Intimacy factor. We
      argue that conceptualizing desire as multifaceted and contextualized when
      assessing hormonal links-or questions in general about desire-can clarify some of
      its complexities and lead to new research avenues.

PMID- 28444532
TI  - The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term
      evaLuAtion (UMBRELLA): objectives, design, and baseline results.
AB  - PURPOSE: In oncology, RCTs are often beset by slow recruitment, limited
      generalizability, and strong preferences for interventions by patients and
      physicians. The cohort multiple randomized controlled trial (cmRCT) is an
      innovative design with the potential to overcome those challenges. In cmRCT, a
      prospective cohort serves as an infrastructure for multiple RCTs. We implemented
      cmRCT in a clinical breast cancer setting by creating UMBRELLA-a large
      prospective cohort of breast cancer and DCIS patients/survivors. METHODS: For all
      participants, clinical data and patient-reported outcomes (PROs, i.e., quality of
      life, fatigue, anxiety and depression, physical activity, work ability, and
      cosmetic satisfaction) are being collected at regular time-intervals for a period
      of 10 years. These data are being used both for observational and randomized
      studies. For each intervention to be tested against standard care, a subcohort of
      eligible patients is identified within UMBRELLA. From this subcohort, a random
      sample of patients is offered the intervention. Their outcomes are compared to
      the outcomes of patients receiving standard care. RESULTS: So far, between
      October 2013 and July 2016, we have recruited 1308 participants. In this period,
      1308/1486 (88%) patients who were invited for participation in UMBRELLA consented
      to cohort participation. Of these patients, 1138 (87%) gave broad consent for
      randomization to future interventions. Return rate for PROs at baseline were 80%,
      and varied from 67 to 74% during follow-up. Several observational studies-and the
      first randomized intervention study-are currently ongoing. CONCLUSIONS: Results
      from UMBRELLA show that this novel study design is feasible and acceptable to
      patients in a clinical breast cancer setting. We invite researchers who are
      interested in conducting randomized or observational studies within the UMBRELLA
      cohort to contact the UMBRELLA scientific advisory board.

PMID- 28444533
TI  - Breast cancer risk models: a comprehensive overview of existing models,
      validation, and clinical applications.
AB  - Numerous models have been developed to quantify the combined effect of various
      risk factors to predict either risk of developing breast cancer, risk of carrying
      a high-risk germline genetic mutation, specifically in the BRCA1 and BRCA2 genes,
      or the risk of both. These breast cancer risk models can be separated into those
      that utilize mainly hormonal and environmental factors and those that focus more
      on hereditary risk. Given the wide range of models from which to choose,
      understanding what each model predicts, the populations for which each is best
      suited to provide risk estimations, the current validation and comparative
      studies that have been performed for each model, and how to apply them
      practically is important for clinicians and researchers seeking to utilize risk
      models in their practice. This review provides a comprehensive guide for those
      seeking to understand and apply breast cancer risk models by summarizing the
      majority of existing breast cancer risk prediction models including the risk
      factors they incorporate, the basic methodology in their development, the
      information each provides, their strengths and limitations, relevant validation
      studies, and how to access each for clinical or investigative purposes.

PMID- 28444534
TI  - Metabolic factors, anthropometric measures, diet, and physical activity in long
      term breast cancer survivors: change from diagnosis and comparison to non-breast
      cancer controls.
AB  - PURPOSE: We studied metabolic factors, diabetes, and anthropometric measurements
      at diagnosis and long-term follow-up (LTFU), mean 12.5 years post-diagnosis, in
      breast cancer (BC) survivors, and compared their status at LTFU to that of age
      matched women without BC. Diet and physical activity were also assessed. METHOD:
      535 non-diabetic BC patients treated at three University of Toronto hospitals
      were followed prospectively; 285 surviving patients, without distant recurrence,
      participated in a LTFU study. A control group of 167 age-matched women without BC
      was recruited from a mammogram screening program at one of the hospitals. Change
      over time was analyzed using paired t tests, and comparisons between BC survivors
      and controls used age and education (AE)-adjusted regression models. RESULTS:
      Median weight gain in BC survivors was 2.00 kg (p < 0.0001); BMI, glucose,
      insulin, homeostasis model assessment (HOMA), and total cholesterol increased
      modestly but significantly. Waist circumference, glucose, and triglycerides were
      higher in LTFU BC survivors versus controls. BC survivors had significantly
      greater prevalence of diabetes/pre-diabetes versus controls (33 vs. 20.4%, AE
      adjusted odds ratio (OR) 1.59, p = 0.050). This effect was restricted to those
      with lower levels of physical activity (<56 metabolic equivalent (MET)
      hours/week: OR 2.70 versus 0.94 for those with higher physical activity,
      interaction p = 0.034). At LTFU, BC survivors were more physically active than at
      diagnosis (median increase 28 MET-hours/week interquartile range -14.8 to 82),
      and compared to controls (median 68.2 vs. 44 MET-hours/week, p < 0.0001).
      CONCLUSION: The prevalence of the metabolic syndrome and diabetes/pre-diabetes
      was significantly higher in BC survivors than in controls group, notably in those
      with lower levels of physical activity. Enhanced diabetes/metabolic syndrome
      screening and promotion of physical activity may be warranted in BC survivors.

PMID- 28444535
TI  - Image analysis of immune cell patterns in the human mammary gland during the
      menstrual cycle refines lymphocytic lobulitis.
AB  - PURPOSE: To improve microscopic evaluation of immune cells relevant in breast
      cancer oncoimmunology, we aim at distinguishing normal infiltration patterns from
      lymphocytic lobulitis by advanced image analysis. We consider potential immune
      cell variations due to the menstrual cycle and oral contraceptives in non
      neoplastic mammary gland tissue. METHODS: Lymphocyte and macrophage distributions
      were analyzed in the anatomical context of the resting mammary gland in
      immunohistochemically stained digital whole slide images obtained from 53
      reduction mammoplasty specimens. Our image analysis workflow included automated
      regions of interest detection, immune cell recognition, and co-registration of
      regions of interest. RESULTS: In normal lobular epithelium, seven CD8[Formula:
      see text] lymphocytes per 100 epithelial cells were present on average and about
      70% of this T-lymphocyte population was lined up along the basal cell layer in
      close proximity to the epithelium. The density of CD8[Formula: see text] T-cell
      was 1.6 fold higher in the luteal than in the follicular phase in spontaneous
      menstrual cycles and 1.4 fold increased under the influence of oral
      contraceptives, and not co-localized with epithelial proliferation. CD4[Formula:
      see text] T-cells were infrequent. Abundant CD163[Formula: see text] macrophages
      were widely spread, including the interstitial compartment, with minor variation
      during the menstrual cycle. CONCLUSIONS: Spatial patterns of different immune
      cell subtypes determine the range of normal, as opposed to inflammatory
      conditions of the breast tissue microenvironment. Advanced image analysis enables
      quantification of hormonal effects, refines lymphocytic lobulitis, and shows
      potential for comprehensive biopsy evaluation in oncoimmunology.

PMID- 28444536
TI  - A Qualitative Look into Israeli Genetic Experts' Insights Regarding Culturally
      Competent Genetic Counseling and Recommendations for Its Enhancement.
AB  - The aim of this study is to describe the perceptions and recommendations of
      Israeli genetic experts in regard to culturally competent genetic counseling.
      Qualitative data was collected from 15 semi-structured interviews with Israeli
      genetics experts. Recurring themes were identified using "thematic analysis" and
      coded by means of "grounded theory". Our analysis divides data from the genetic
      experts' interviews into four main themes: Why is culturally competent genetic
      counseling important? (Describing its contribution to individuals and to
      society); who is the recipient of culturally competent genetic counseling?
      (Differentiating the needs of counselees based on genetic education,
      cultural/religious characteristics and geographic location); what should we
      include in culturally competent genetic counseling? (Addressing the contents that
      counseling should convey); how should we perform culturally competent genetic
      counseling? (Addressing the methods that counseling should employ). In light of
      the study, we recommend lengthening the genetic counseling session so that
      counselors will be able to truly gauge all the prior knowledge of the counselees,
      their religious beliefs, norms, values and attitudes towards genetic testing. We
      further recommend that students continue to study genetics further into high
      school. Finally, we suggest adding a preparation session, similar to a prenatal
      course, to the genetic counseling of lay people so that their genetic knowledge,
      attitudes and perceptions will be enhanced, leading to more efficient genetic
      counseling and more informed decisions.

PMID- 28444537
TI  - Molecular characterization of a novel bipartite begomovirus isolated from
      Lycianthes biflora in China.
AB  - A bipartite begomovirus isolate GD was isolated from Lycianthes biflora plants
      showing yellow mosaic symptoms in Nanxiong, Guangdong Province, China. The
      apparently full-length DNA-A and DNA-B viral components were cloned after
      enrichment of circular DNA by rolling circle amplification, restriction
      digestion, cloning, and DNA sequencing. The DNA-A component (2752nt, KT582302)
      shares highest (80.2%) nucleotide (nt) sequence identity with tomato leaf curl
      Sulawesi virus [Indonesia-Sulawesi-Langowan F101-2006] (ToLCSuV- [ID-Sul -LanF09
      06], FJ237618), reported in Indonesia as causing yellow leaf curl disease of
      chilli pepper. The DNA-B component (2704nt, KT582303) shares highest (76.3%) nt
      sequence identity with pepper yellow leaf curl Indonesia virus-[Indonesia-tomato2
      2005] (PepYLCIV-[ID-Tom2-05 AB213599) reported in Indonesia, and associated with
      yellow leaf curl disease in tomato. Based on the ICTV guidelines for begomoviral
      species demarcation, the virus is a new, previously undescribed bipartite
      begomovirus species for which the name "Lycianthes yellow mosaic virus" is
      proposed.

PMID- 28444538
TI  - Occurrence and genetic diversity analysis of apple stem pitting virus isolated
      from apples in China.
AB  - Two primer pairs were used to detect apple stem pitting virus (ASPV) using a
      reverse transcription (RT)-PCR test. 82 out of the 141 randomly collected
      samples, from ten orchards in five provinces and regions of China, tested
      positive. In the positive samples forty-five (55%) were infected by ASPV and two
      other viruses. The full coat protein (CP) and the triple gene block (TGB) gene 1,
      2 and 3 of partial ASPV isolates were subsequently cloned. The nucleotide and
      amino acid identities of 39 CP sequence variants from 31 Chinese apple samples
      were compared with that of previously reported ASPV isolates and were 67.4-96.0%
      and 68.4-97.7%, respectively. All ASPV sequence variants from Chinese apples
      separated into two clades with CP- and TGB-based phylogenetic trees, whilst the
      grouping of TGB2 and TGB3 trees was the same. Three recombinants (FS06-2, X5-2,
      and XLF-C-2) for CP and six (TH2-5, X8-2, FS05-2, X6-2 and XLF-A-1) recombinants
      for TGB were identified from the Chinese apple isolates. Two recombinants were
      found in the TGB sequence of isolate XLF-A-1. The results presented here may
      assist in the development of a more comprehensive screening tool for apple
      viruses.

PMID- 28444539
TI  - Association of the OAS3 rs1859330 G/A genetic polymorphism with severity of
      enterovirus-71 infection in Chinese Han children.
AB  - The 2'5'-oligoadenylate synthetase (OAS) is an interferon (IFN)-induced protein
      that plays an important role in the antiviral action of IFN, with OAS3 being one
      of the four OAS classes (OAS1, OAS2, OAS3, OASL). The effect of OAS on several
      infectious viral diseases has been reported; however, a study of the effect of
      OAS3 on enterovirus 71 (EV71) is lacking. The purpose of this study was to
      evaluate the association of the OAS3 rs1859330 G/A genetic polymorphism with
      susceptibility and severity of EV71 infection. We investigated 370 Chinese Han
      children with hand-foot-mouth disease (HFMD) (214 of which were mild cases while
      156 were severe). An improved multiplex ligation detection reaction (iMLDR)
      technique was carried out to examine the genotype. The AA genotype distribution
      (p = 0.002) and A allele frequency (OR = 1.83, 95% CI 1.32-2.52, p < 0.001) of
      OAS3 rs1859330 in severe cases were significantly higher than in mild cases. When
      comparing the different genotypes in EV71-infected patients, there were
      statistical differences in relation to rash (p = 0.03), oral ulcers (p = 0.005),
      pathologic reflex (p = 0.003), WBC counts (p = 0.032), CRP (p = 0.024), BG
      concentrations (p = 0.029), ALT (p = 0.02), and EEG (p = 0.019). However, there
      were no differences in relation to age, gender, AST, CK-MB, CT/ MRI, as well as
      some symptoms and signs (e.g. duration of fever (days), headache, convulsions,
      consciousness disturbance, paralysis, sign of meningeal irritation). In the
      cerebrospinal fluid (CSF) of severe cases, there were no differences in the
      levels of white cells, protein, glucose, chloride, lymphocytes and monocytes
      between the different genotypes. The plasma levels of IFN-gamma in EV71-infected
      patients were significantly higher than in the control group (p < 0.01). IFN
      gamma concentrations in severe cases were lower in A allele carriers (AA+GA)
      (118.5 +/- 12.6pg/mL) than in GG homozygotes (152.6 +/- 56.3pg/mL p < 0.05).
      These findings suggest that the OAS3 rs1859330 G/A genetic polymorphism is
      associated with the severity of EV-71 infection, and that the A allele is a risk
      factor for the development of severe EV71 infection.

PMID- 28444540
TI  - Impact of residual disease after "unplanned excision" of primary localized adult
      soft tissue sarcoma of the extremities: evaluation of 452 cases at a single
      Institution.
AB  - BACKGROUND: Soft tissue sarcomas are often inappropriately excised; it is,
      however, still a matter of debate whether the presence of residual disease in the
      re-excision specimen can affect patients' prognosis. The aim of this study is to
      investigate the impact of re-excision after unplanned surgery of primary soft
      tissue sarcomas (STS) of the extremities. PATIENTS AND METHODS: We
      retrospectively evaluated 452 adults with grade 2-3, localized STS (349 primary
      and 103 unplanned excisions). RESULTS: In the re-excision group, a full 43% of
      the patients had residual tumor. The re-excision group achieved a significantly
      better outcome in terms of sarcoma-specific survival (SS) (p = 0.002), local
      recurrence (LR) (p = 0.004) and distant metastasis (DM) (p = 0.028). Residual
      tumor was associated with a higher risk of DM (p = 0.005). CONCLUSION: We confirm
      that unplanned surgery does not compromise patients' prognosis; scar re-excision
      guarantees at least the same SS, LR and DM rates compared to STS primarily
      treated in a referral center. Routine use of radiation therapy after re-excision
      could improve local control. Distant metastases seem to be negatively affected by
      the presence of residual tumor, and therefore, the use of CT in deep and large
      STS is suggested. The main goal is to avoid unplanned surgery by referring
      suspected lumps (especially deep, large, increasing in size) to a specialist
      center.

PMID- 28444541
TI  - Reverse shoulder arthroplasty for massive irreparable rotator cuff tears and cuff
      tear arthropathy: a systematic review.
AB  - PURPOSE: To report the outcomes and complications of reverse shoulder
      arthroplasty (RSA) in massive irreparable rotator cuff tears (MIRCT) and cuff
      tear arthropathy (CTA). METHODS: A systematic review of the literature contained
      in Medline, Cochrane, EMBASE, Google Scholar and Ovid databases was conducted on
      May 1, 2016, according to PRISMA guidelines. The key words "reverse total
      shoulder arthroplasty" or "reverse total shoulder prostheses" with "rotator cuff
      tears"; "failed rotator cuff surgery"; "massive rotator cuff tears"; "irreparable
      rotator cuff tears"; "cuff tear arthropathy"; "outcomes"; "complications" were
      matched. All articles reporting outcomes and complications of RSA for the
      management of MIRCT or CTA were included. The comparison between preoperative and
      postoperative clinical scores, as well as range of motion (ROM), was performed
      using the Wilcoxon-Mann-Whitney test. P values lower than 0.05 were considered
      statistically significant. RESULTS: Seven articles were included in our
      qualitative synthesis. A statistically significant improvement in all clinical
      scores and ROM was found comparing the preoperative value with the postoperative
      value. The degrees of retroversion of the humeral stem of the RSA do not
      influence the functional outcomes in a statistically significant fashion. There
      were 17.4% of complications. The most frequent was heterotopic ossification,
      occurring in 6.6% of patients. Revision surgery was necessary in 7.3% of
      patients. CONCLUSIONS: RSA restores pain-free ROM and improves function of the
      shoulder in patients with MIRCT or CTA. However, complications occur in a high
      percentage of patients. The lack of level I studies limits the real understanding
      of the potentials and limitations of RSA for the management of MIRCT and CTA.

PMID- 28444542
TI  - Risk factors for postoperative hypocalcemia.
AB  - Hypocalcaemia is one of the most common complications after thyroidectomy;
      however, it is still unclear what preoperative factors could predict this event.
      The aim of this study was to evaluate the role of risk factors for hypocalcaemia
      after total thyroidectomy (TT). Consecutive patients who underwent total
      thyroidectomyat our institution between January 2014 and January 2016 were
      enrolled. The clinical and pathologic characteristics and surgical details of
      normocalcemic and hypocalcemic patients were compared. Univariate and
      multivariate analyses to estimate risk ratio were assessed. A total of 328
      patients underwent TT; histology revealed benign and malignant disease in 83 and
      17% of cases, respectively. Central-compartment neck dissection (CCND) was
      performed in 36 subjects (10.9%). Parathyroid glands were observed in 23% (76) of
      specimens. Laboratory asymptomatic hypocalcaemia was observed in 92 (28%)
      patients; symptomatic hypocalcaemia occurred in 26 (7.9%). Transient
      hypocalcaemia has been observed in 48 (14.6%) patients; permanent hypocalcaemia
      occurred in two subjects (0.6%). On univariate analysis, malignant pathology (p <
      0.001), CCND (p < 0.05), female gender (p < 0.001), presence of at least two
      parathyroid glands in specimens (p < 0.002), and operative time longer than 120
      min (p < 0.05) were factors that significantly increased the risk of developing
      asymptomatic and transient hypocalcaemia. After logistic regression analysis,
      malignant pathology (p < 0.000; p < 0.001) and CCND (p < 0.005; p = 0.013) were
      the significant factors that affected the development of symptomatic and
      transient hypocalcaemia. The presence of malignant pathology and CCND was found
      to be significant risks factors for postoperative hypocalcaemia. In patients in
      whom this pathological features are present, attention should be paid to rapidly
      start an adequate therapy.

PMID- 28444543
TI  - Cost analysis of incisional hernia repair with synthetic mesh and biological
      mesh: an Italian study.
AB  - Repair of an incisional hernia (IH) generates costs on several levels and domains
      of society. The aim of this study was to make a complete cost analysis of
      incisional hernia repair (IHR) with synthetic and biological mesh and to compare
      it with financial reimbursement. Patients were grouped into three levels to
      determine the complexity of their care, and hence, the costs involved. Group 1
      included patients without comorbidities, who underwent a "standard" incisional
      hernia repair (SIHR), with synthetic mesh. Group 2 included patients with
      comorbidities, who underwent the same surgical procedure. Group 3 included all
      patients who underwent a "complex" IHR (CIHR) with biological mesh. Total costs
      were divided into direct (including preoperative and operative phases) and
      indirect costs (medications and working days loss). Reimbursement was calculated
      according to Diagnosis-Related Group (DRG). From 2012 to 2014, 76 patients
      underwent prosthetic IHR: group 1 (35 pts); group 2 (30 pts); and group 3 (11
      pts). The direct costs of preoperative and operative phases for groups 1 and 2
      were ?5544.25 and ?5020.65, respectively, and ?16,397.17 in group 3. The total
      reimbursement in the three groups was ?68,292.37 for group 1, ?80,014.14 for
      group 2, and ?72,173.79 for group 3, with a total loss of ?124,658.43,
      ?69,675.36, and ?100,620.04, respectively. All DRGs underestimate the costs
      related to IHR and CIHR, thus resulting in an important economic loss for the
      hospital. The cost analysis shows that patient-related risk factors do not alter
      the overall costs. To provide a correct "cost-based" reimbursement, different
      DRGs should be created for different types of hernias and prostheses.

PMID- 28444545
TI  - Erratum to: Braf, Kras and Helicobacter pylori epigenetic changes-associated
      chronic gastritis in Egyptian patients with and without gastric cancer.

PMID- 28444546
TI  - Continuous magnesium infusions in the management of systemic anti-cancer therapy
      related hypomagnesaemia.
AB  - : Background Hypomagnesaemia is a relatively-common side effect of some systemic
      anti-cancer therapies (SACT). Oral and intravenous magnesium (given as injections
      or short infusions) have problems arising from their poor tolerability, and need
      for frequent administrations, respectively. Objective Assessing the effectiveness
      and safety of weekly continuous magnesium infusions (CMI) in the management of
      SACT-related hypomagnesaemia. Methods CMIs (initiated at 10 mmol/day and up
      titrated subject to response) were prescribed to patients with >=3 magnesium
      readings <0.5 mmol/L despite intravenous replacement with bolus-or-short
      infusions (BSI). Efficacy (compared to BSI): (a) reduction in the number of
      moderate/severe hypomagnesaemia episodes, and (b) increase in mean magnesium
      serum levels. SAFETY: non-occurrence of grade >=3 toxicities (according to the
      common terminology criteria for adverse events v4). Results Three patients were
      treated (mean age: 62-years), pre-SACT levels were 0.629 +/- 0.121 mmol/L.
      EFFICACY: (a) 1 versus 18 episodes; (b) 0.639 +/- 0.093 mmol/L versus 0.533 +/-
      0.191 mmol/L. All comparisons were statistically significant in favour of CMI (p
      < 0.001). No magnesium-related grade >=2 side effects were observed. Conclusion
      CMIs resulted in a marked reduction in the number of episodes of hypomagnesaemia
      and higher magnesium levels, with no significant side effects. CMIs represent a
      potential option for the management of SACT-related hypomagnesaemia, although
      further research in an expanded cohort is required.

PMID- 28444544
TI  - Methylglyoxal detoxification by a DJ-1 family protein provides dual abiotic and
      biotic stress tolerance in transgenic plants.
AB  - Methylglyoxal (MG) is a key signaling molecule resulting from glycolysis and
      other metabolic pathways. During abiotic stress, MG levels accumulate to toxic
      levels in affected cells. However, MG is routinely detoxified through the action
      of DJ1/PARK7/Hsp31 proteins that are highly conserved across kingdoms and
      mutations in such genes are associated with neurodegenerative diseases. Here, we
      report for the first time that, similar to abiotic stresses, MG levels increase
      during biotic stresses in plants, likely contributing to enhanced susceptibility
      to a wide range of stresses. We show that overexpression of yeast Heat shock
      protein 31 (Hsp31), a DJ-1 homolog with robust MG detoxifying capabilities,
      confers dual biotic and abiotic stress tolerance in model plant Nicotiana
      tabacum. Strikingly, overexpression of Hsp31 in tobacco imparts robust stress
      tolerance against diverse biotic stress inducers such as viruses, bacteria and
      fungi, in addition to tolerance against a range of abiotic stress inducers.
      During stress, Hsp31 was targeted to mitochondria and induced expression of key
      stress-related genes. These results indicate that Hsp31 is a novel attractive
      tool to engineer plants against both biotic and abiotic stresses.

PMID- 28444548
TI  - Post-Effect of Air Quality Improvement on Biomarkers for Systemic Inflammation
      and Microparticles in Asthma Patients After the 2008 Beijing Olympic Games: a
      Pilot Study.
AB  - This study's aim was to investigate the post-effect of an air quality improvement
      on systemic inflammation and circulating microparticles in asthmatic patients
      during, and 2 months after, the Beijing Olympics 2008. We measured the levels of
      circulating inflammatory cytokines and microparticles in the peripheral blood
      from asthma patients and healthy controls during (phase 1), and 2 months after
      (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating
      cytokines (including TNFalpha, IL-6, IL-8, and IL-10) were still seen reduced in
      phase 2 when compared with those in phase 1. The number of circulating
      endothelial cell-derived microparticles was significantly lower during the phase
      2 than that during phase 1 in asthma patients. The level of plasma
      lipopolysaccharide-binding protein (LBP) was significantly decreased in
      asthmatics in phase 2. The level of norepinephrine was significantly higher in
      phase 2 than that in phase 1 in plasma from both asthma patients and healthy
      subjects. There were no significant differences in the gene profile for the toll
      like receptor (TLR) signaling from peripheral blood mononuclear cells. In vitro,
      microvesicles from patients with asthma impaired the relaxation to bradykinin and
      contraction to acetylcholine, whereas microparticles from healthy subjects did
      not. These data suggested that reduction in systemic pro-inflammatory responses
      and circulating LBP and increased level of norepinephrine in asthma patients
      persisted even after 2 months of the air pollution intervention. These changes
      were independent of the TLR signaling pathway. Circulating microparticles might
      be associated with airway smooth muscle dysfunction.

PMID- 28444549
TI  - Comparison of in-stent neoatherosclerosis and tissue characteristics between
      early and late in-stent restenosis in second-generation drug-eluting stents: an
      optical coherence tomography study.
AB  - Optical frequency domain imaging (OFDI) was utilized to compare the prevalence of
      neoatherosclerosis (NA) and morphological characteristics of the neointimal
      tissue in second generation drug eluting stent (G2-DES)-treated lesions between
      early (<1 year, E-ISR) and late (>1 year, L-ISR) in-stent restenotic phases. Data
      comparing NA and in vivo tissue characteristics between early and late in-stent
      restenosis (ISR) after implantation of G2-DES is limited. An OFDI analysis was
      performed in 50 G2-DESs {35 everolimus-eluting stent [22 cobalt-chromium (CoCr),
      13 platinum-chromium (PtCr)], and 15 biolimus-eluting stent [BES]} ISR lesions
      (46 consecutive patients) undergoing target lesion revascularization, classified
      as E-ISR (n = 22 lesion) and L-ISR (n = 28 lesion). NA, defined as a neointima
      formation containing lipids or calcification was observed in fewer than half
      (24/50) of all ISR lesions with no significant difference between E-ISR and L-ISR
      lesions (50 vs. 46.4%, p = 0.8). There were also no significant differences in
      the morphological appearance and tissue characteristics between E-ISR and L-ISR
      lesions. ISR was more likely to occur earlier [median 8.6 (8.3-8.9) months] after
      PtCr-EES implantations (12 lesions vs. 1, p < 0.001), while 3/4 of the BES ISR
      lesions and more than 2/3 of the CoCr-EES ISR lesions were observed after 1 year
      of implantation [median 21.3 (20.7-27.5) months, p < 0.001]. Acknowledging some
      limitations, our observations may suggest that the prevalence of
      neoatherosclerosis and the morphological appearance, and tissue characteristics
      of G2-DESs restenotic lesions are similar between the early and late restenotic
      phases. Certain platforms (PtCr-EESs) may have preferentially presented with
      early ISR.

PMID- 28444550
TI  - Glottic impersonation, perhaps, but direct visualization remains vital to confirm
      successful intubation.

PMID- 28444551
TI  - In reply: Glottic impersonation, perhaps, but direct visualization remains vital
      to confirm successful intubation.

PMID- 28444553
TI  - Measuring hemophilia caregiver burden: validation of the Hemophilia Caregiver
      Impact measure.
AB  - AIMS: The purpose of this article is to describe the psychometric development of
      the Hemophilia Caregiver Impact measure. METHODS: Qualitative interviews (n = 22)
      and a cross-sectional web-based study (n = 458) were implemented with caregivers
      of people with hemophilia. Classical test theory and item response theory
      analyses were implemented to evaluate the psychometric characteristics of the
      measure. RESULTS: The study sample had a mean age of 39 and a median level of
      college education. It was predominantly female (88%), and had an average of two
      children. 85% of this study sample had at least one child with hemophilia. The
      final 36-item Hemophilia Caregiver Impact measure is composed of seven subscales
      assessing relevant negative aspects of caregiver impact (Burden Summary) as well
      as one subscale reflecting a positive aspect of caregiver impact (Positive
      Emotions). These two summary scores are orthogonal and can be used together in
      analyses examining negative and positive aspects of caregiver impact. The items
      included within each subscale reflect a unidimensional construct, demonstrate
      good item information and trace lines, and lack of local dependence. The
      resulting subscales demonstrate high reliability, and good construct validity.
      They show moderate incremental and discriminant validity. CONCLUSIONS: The
      Hemophilia Caregiver Impact measure is a useful new tool for clinical research on
      hemophilia. In addition to having eight relevant subscales, the measure can also
      be summarized with two scores. This versatility can be useful in analyzing
      studies with very small samples, which is to be expected when dealing with a rare
      condition like hemophilia.

PMID- 28444552
TI  - Income and health-related quality of life among prostate cancer patients over a
      one-year period after radical prostatectomy: a linear mixed model analysis.
AB  - PURPOSE: To examine income-related disparities in health-related quality of life
      (HRQOL) over a one-year period after surgery (radical prostatectomy) and its
      contributory factors in a longitudinal perspective. Evidence of associations
      between income and HRQOL among patients with prostate cancer (PCa) is sparse and
      their explanations still remain unclear. METHODS: 246 males of two German
      hospitals filled out a questionnaire at the time of acute treatment, 6 and 12
      months later. Age, partnership status, baseline disease and treatment factors,
      physical and psychological comorbidities, as well as treatment factors and
      adverse effects at follow-up were additionally included in the analyses to
      explain potential disparities. HRQOL was assessed with the EORTC (European
      Organisation for Research and Treatment of Cancer) QLQ-C30 core questionnaire and
      the prostate-specific QLQ-PR25. A linear mixed model for repeated measures was
      calculated. RESULTS: The fixed effects showed highly significant income-related
      inequalities regarding the majority of HRQOL scales. Less affluent PCa patients
      reported lower HRQOL in terms of global quality of life, all functional scales
      and urinary symptoms. After introducing relevant covariates, some associations
      became insignificant (physical, cognitive and sexual function), while others only
      showed reduced estimates (global quality of life, urinary symptoms, role,
      emotional and social function). In particular, mental disorders/psychological
      comorbidity played a relevant role in the explanation of income-related
      disparities. CONCLUSIONS: One year after surgery, income-related disparities in
      various dimensions of HRQOL persist. With respect to economically disadvantaged
      PCa patients, the findings emphasize the importance of continuous psychosocial
      screening and tailored interventions, of patients' empowerment and improved
      access to supportive care.

PMID- 28444554
TI  - Relationships between environmental factors and participation in adults with
      traumatic brain injury, stroke, and spinal cord injury: a cross-sectional multi
      center study.
AB  - PURPOSE: To develop and evaluate a model of environmental factors-participation
      relationships for persons with traumatic brain injury (TBI), stroke, and spinal
      cord injury (SCI), and test whether this model differed across three diagnostic
      groups, as well as other demographic and clinical characteristics. METHODS: A
      cross-sectional observational study included 545 community-dwelling adults with
      neurological disorders (TBI = 166; stroke = 189; SCI = 190) recruited at three
      academic medical centers. Participants completed patient-reported measures of
      environmental factors and participation. RESULTS: The final structural equation
      model had acceptable fit to the data (CFI = 0.923; TLI = 0.898; RMSEA = 0.085;
      SRMR = 0.053), explaining 63% of the variance in participation in social roles
      and activities. Systems, services, and policies had an indirect influence on
      participation and this relation was mediated by social attitudes and the built
      and natural environment. Access to information and technology was associated with
      the built and natural environment which in turn influence on participation (ps <
      0.001). The model was consistent across sex, diagnosis, severity/type of injury,
      education, race, age, marital status, years since injury, wheelchairs use,
      insurance coverage, personal or household income, and crystallized cognition.
      CONCLUSIONS: Social and physical environments appear to mediate the influence of
      systems, services, and policies on participation after acquired neurological
      disorders. These relations are stable across three diagnostic groups and many
      personal and clinical factors. Our findings inform health and disability policy,
      and provide guidance for implementing the initiatives in Healthy People 2020 in
      particular for people with acquired neurological disorders.

PMID- 28444555
TI  - Evaluating the effectiveness of a novel atomized liquid needle-free transdermal
      delivery system.
AB  - Needle-free jet injections constitute a crucial method for drug delivery. A novel
      liquid drug delivery system has been proposed recently, in which pressure
      atomizes liquid before delivering that atomized liquid to the patient's body;
      however, the mechanism and efficiency of the system are unclear. This study
      explored the shot delivery pressure, penetration depth, and cumulative amount of
      permeation of this system. This system was used to deliver 0.5% (w/v) methylene
      blue to agarose phantoms at various shot delivery pressures. Shots of methylene
      blue were also delivered to porcine skin samples at different shot delivery
      frequencies for light microscopy evaluation. A commercial microneedle array was
      used for comparing the effectiveness of the skin penetration depths. The array
      was gently stamped against porcine skin; methylene blue was subsequently applied
      to the area for different time points, followed by microscopic observations. In
      vitro skin penetration was tested using static Franz diffusion cells over 8 h.
      Finally, the feasibility of the system's clinical application was evaluated by
      analyzing the local analgesic effect in a heat nociceptive animal model. The
      penetration depths created using 100 shots at 100 psi were similar to those
      created using the commercial microneedle array for 2 h. Thermal stimulation
      responses showed that 15 min after diclofenac sodium was delivered by the system,
      heat nociception was significantly attenuated for 60 min. Our study presents a
      novel delivery system that may be useful for future clinical applications.

PMID- 28444556
TI  - Thalamo-cortical functional connectivity in schizophrenia and bipolar disorder.
AB  - The thalamus is a highly connected subcortical structure that relays and
      integrates sensory and cortical information, which is critical for coherent and
      accurate perceptual awareness and cognition. Thalamic dysfunction is a classical
      finding in schizophrenia (SZ), and resting-state functional MRI has implicated
      somatomotor and frontal lobe thalamic dysconnectivity. However, it remains
      unclear whether these findings generalize to different psychotic disorders, are
      confined to specific thalamic sub-regions, and how they relate to structural
      thalamic alterations. Within-thalamic and thalamo-cortical functional
      connectivity was assessed using resting-state functional MRI data obtained from
      patients with SZ (n = 96), bipolar disorder (BD, n = 57), and healthy controls
      (HC, n = 280). Further, we used thalamic sub-regions as seeds to investigate
      specific cortical connectivity patterns, and performed structural analyses of
      thalamic volume and shape. Results showed reduced within-thalamic connectivity
      and thalamo-frontoparietal coupling in SZ and increased thalamo-somatomotor
      connectivity in BD. One thalamic sub-region showed increased sensory connectivity
      in SZ and eight sub-regions showed reductions with frontal and posterior areas.
      Reduced gray matter and shape abnormalities were found in frontal-projecting
      regions in both SZ and BD, but did not seem to explain reduced functional
      connectivity. Aberrant thalamo-cortical connectivity patterns in SZ and BD
      supports the notion of the thalamus as a key structure in the functional
      connectome across the psychosis spectrum, and the frontal and somatomotor
      anatomical distribution is in line with the characteristic cognitive and
      perceptual symptoms in psychotic disorders.

PMID- 28444558
TI  - Evolution of Surgical Treatment for Rectal Cancer: a Review.
AB  - Surgery that produces an optimal total mesorectal excision (TME) resection
      specimen remains the cornerstone of curative rectal cancer management. In the
      modern era, despite the results of recent randomised trials, laparoscopic TME is
      a crucial technique in the TME surgery armamentarium. Laparoscopic surgery offers
      the benefit of magnified views that aid sharp and precise dissection. However
      operating in the confines of a narrow pelvis, particularly when the mesorectum is
      bulky, requires significant technical skill. This is compounded by limited
      angulation of laparoscopic instruments and staplers. The final challenge is to
      preserve the integrity of the mesorectum during delivery of the specimen. The
      principles of TME surgery, on which Bill Heald founded the Basingstoke Colorectal
      unit, can equally be applied to laparoscopic, transanal and robotic TME, but
      great care must be taken to preserve the key principle-that no steps are taken
      that have the potential to shed tumour cells or compromise the quality of the
      mesorectal specimen.

PMID- 28444559
TI  - Effectiveness of an Interdisciplinary Medical Hospital Admission Center: The Role
      of the Dental Section in the Interdisciplinary System for Perioperative
      Management of Patients Awaiting Surgery.
AB  - Perioperative oral functional management (POFM) involves total oral management of
      a patient before surgery. Considerable benefits have been reported, but POFM
      remains scarce in medical settings. An interdisciplinary Medical Hospital
      Admission Center (MHAC) opened in our hospital in December 2014, and has since
      provided unified perioperative management for patients. This study reports on the
      clinical system and contributions of the systematized, standardized POFM applied
      through the MHAC. Patients awaiting surgery undergo oral screening before
      admission, with patients classified into three groups: red, needing surgical oral
      management (tooth extraction or other oral surgery) before surgery; yellow,
      needing non-surgical oral management before surgery, due to the planned surgery
      or the risk of tooth injury in connection with general anesthesia; or green,
      patients with good oral hygiene considered capable of suitable oral self
      management. Patients categorized as red or yellow undergo POFM in the dental
      section of the MHAC before surgery. Almost all patients (88.8%) awaiting surgery
      now undergo preoperative oral screening, excluding emergent surgeries. In
      addition, oral screening is important for preventing tooth injury during
      endotracheal intubation for general anesthesia, and a need for preventive
      measures was identified in 6.1% of patients. No traumatic injuries of the teeth
      in connection with general anesthesia have occurred since the opening of the
      MHAC. Standardized POFM through an interdisciplinary MHAC thus seems extremely
      useful.

PMID- 28444557
TI  - Overview on the Current Status of Zika Virus Pathogenesis and Animal Related
      Research.
AB  - There is growing evidence that Zika virus (ZIKV) infection is linked with
      activation of Guillan-Barre syndrome (GBS) in adults infected with the virus and
      microcephaly in infants following maternal infection. With the recent outpour in
      publications by numerous research labs, the association between microcephaly in
      newborns and ZIKV has become very apparent in which large numbers of viral
      particles were found in the central nervous tissue of an electively aborted
      microcephalic ZIKV-infected fetus. However, the underlying related mechanisms
      remain poorly understood. Thus, development of ZIKV-infected animal models are
      urgently required. The need to develop drugs and vaccines of high efficacy along
      with efficient diagnostic tools for ZIKV treatment and management raised the
      demand for a very selective animal model for exploring ZIKV pathogenesis and
      related mechanisms. In this review, we describe recent advances in animal models
      developed for studying ZIKV pathogenesis and evaluating potential interventions
      against human infection, including during pregnancy. The current research
      directions and the scientific challenges ahead in developing effective vaccines
      and therapeutics are also discussed.

PMID- 28444560
TI  - Y-chromosomal sequences of diverse Indian populations and the ancestry of the
      Andamanese.
AB  - We present 42 new Y-chromosomal sequences from diverse Indian tribal and non
      tribal populations, including the Jarawa and Onge from the Andaman Islands, which
      are analysed within a calibrated Y-chromosomal phylogeny incorporating South
      Asian (in total 305 individuals) and worldwide (in total 1286 individuals) data
      from the 1000 Genomes Project. In contrast to the more ancient ancestry in the
      South than in the North that has been claimed, we detected very similar
      coalescence times within Northern and Southern non-tribal Indian populations. A
      closest neighbour analysis in the phylogeny showed that Indian populations have
      an affinity towards Southern European populations and that the time of divergence
      from these populations substantially predated the Indo-European migration into
      India, probably reflecting ancient shared ancestry rather than the Indo-European
      migration, which had little effect on Indian male lineages. Among the tribal
      populations, the Birhor (Austro-Asiatic-speaking) and Irula (Dravidian-speaking)
      are the nearest neighbours of South Asian non-tribal populations, with a common
      origin in the last few millennia. In contrast, the Riang (Tibeto-Burman-speaking)
      and Andamanese have their nearest neighbour lineages in East Asia. The Jarawa and
      Onge shared haplogroup D lineages with each other within the last ~7000 years,
      but had diverged from Japanese haplogroup D Y-chromosomes ~53000 years ago, most
      likely by a split from a shared ancestral population. This analysis suggests that
      Indian populations have complex ancestry which cannot be explained by a single
      expansion model.

PMID- 28444561
TI  - A rare variant in the FHL1 gene associated with X-linked recessive
      hypoparathyroidism.
AB  - Isolated familial hypoparathyroidism is an extremely rare disorder, which to date
      has been linked to several loci including mutations in CASR, GCM2, and PTH, as
      well as a rare condition defined as X-linked recessive hypoparathyroidism,
      previously associated with a 1.5 Mb region on Xq26-q27. Here, we report a patient
      with hypocalcemia-induced seizures leading to the diagnosis of primary
      hypoparathyroidism. Mutations in CASR, GCM2, and PTH were ruled out, while whole
      exome sequencing of the family suggested FHL1, located on chromosome Xq26, as the
      most likely causative gene variant (FHL1, exon 4, c.C283T, p.R95W). Since FHL1
      has not been linked to calcium regulation before, we provide evidence for its
      functional role in hypoparathyroidism by: (i) bioinformatics analysis coupling
      its action to known modulators of PTH function; (ii) observing strong expression
      of fhl1b in Corpuscles of Stannius, gland-like aggregates in zebrafish that
      function in calcium regulation similar to mammalian PTH; and (iii) implicating
      fhl1b and FHL1 as regulators of calcium homeostasis in zebrafish and human cells,
      respectively. Altogether, our data suggest that FHL1 is a novel regulator of
      calcium homeostasis and implicate it as the causative gene for X-linked recessive
      hypoparathyroidism.

PMID- 28444562
TI  - Infliximab Maintenance Dosing in Inflammatory Bowel Disease: an Example for In
      Silico Assessment of Adaptive Dosing Strategies.
AB  - Infliximab is an anti-tumour necrosis factor alpha monoclonal antibody used to
      treat inflammatory diseases. Many patients fail during induction and others
      respond initially but relapse during maintenance therapy. Although anti-drug
      antibodies (ADA) are associated with some clinical failures, there is evidence
      that some failures may be due to subtherapeutic exposure. Adapting doses based on
      clinical outcomes and trough concentrations can improve response and reduce the
      proportion that develop ADA, but identification of appropriate doses in the
      presence of time-varying patient factors is complicated. Several adaptive dosing
      strategies (label recommendations versus therapeutic drug monitoring with an
      established stepwise algorithm or proportional dose adjustments or Bayesian
      population pharmacokinetic model-based dosing) were simulated on a virtual
      population (constructed with time-varying covariates and random effects on
      individual pharmacokinetic parameters) using R to assess their relative
      performance. Strategies were evaluated on their ability to maintain trough
      infliximab concentrations above an established target, 3 mg/L, during maintenance
      phase. Model-based dosing was superior in maintaining target trough
      concentrations, showing individuals in maintenance achieving concentrations above
      the target faster and a lower proportion of individuals who developed ADA. Model
      based dosing results were consistent across a range of baseline covariate groups.
      This in silico assessment of adaptive dosing strategies demonstrated that, when
      challenged with dynamic covariate and random effect changes occurring in
      individual pharmacokinetic parameters, model-based approaches were superior to
      other strategies. Model-based dosing has not been tested clinically; however, the
      potential benefits of model-based dosing for infliximab suggest that it should be
      investigated to reduce subtherapeutic exposure.

PMID- 28444563
TI  - 889 days of support on hydrodynamic bearing rotation mode of the DuraHeartTM for
      bridge-to-heart transplantation.
AB  - A 49-year-old man with ischemic cardiomyopathy and tricuspid regurgitation
      underwent a DuraHeart implantation and tricuspid annuloplasty for bridge-to-heart
      transplantation. On postoperative day 393, the magnetic levitation system
      suddenly broke down, and the pump system went into hydrodynamic bearing rotation
      (HD) mode without causing relevant symptoms. The controller was exchanged with
      one that adapted to the HD mode. No significant hemodynamic changes or
      indications of hemolysis were observed. On postoperative day 982, the pump
      temporarily stopped nine times. The patient refused pump exchange despite our
      strong recommendation for it. After 1283 days of DuraHeart support (889 days in
      HD mode) without hemolysis or neurologic events, he underwent heart
      transplantation. The DuraHeart manufacturer's analysis revealed much damage to
      the insulation and fatigue fractures of the conductors, which had resulted in
      temporary cessation of function and failure of the magnetic levitation system.
      This was a rare case of long-term support under the DuraHeart HD mode.

PMID- 28444564
TI  - Response to lead pollution: mycorrhizal Pinus sylvestris forms the biomineral
      pyromorphite in roots and needles.
AB  - The development of mycorrhized pine seedlings grown in the presence of lead was
      assessed in order to investigate how higher plants can tolerate lead pollution in
      the environment. Examination with scanning electron microscopy (SEM) revealed
      that Pb uptake was prominent in the roots, while a smaller amount was found in
      pine needles, which requires symplastic uptake and root-to-shoot transfer. Lead
      was concentrated in nanocrystalline aggregates attached to the cell wall and,
      according to elemental microanalyses, is associated with phosphorus and chlorine.
      The identification of the nanocrystalline phase in roots and needles was
      performed by transmission electron microscopy (TEM) and synchrotron X-ray micro
      diffraction (MU-XRD), revealing the presence of pyromorphite, Pb5[PO4]3(Cl, OH),
      in both roots and needles. The extracellular embedding of pyromorphite within
      plant cell walls, featuring an indented appearance of the cell wall due to a
      callus-like outcrop of minerals, suggests a biogenic origin. This
      biomineralization is interpreted as a defense mechanism of the plant against lead
      pollution.

PMID- 28444565
TI  - Technological applications of organo-montmorillonites in the removal of
      pyrimethanil from water: adsorption/desorption and flocculation studies.
AB  - Pyrimethanil (2-aniline-4, 6-dimethylpyrimidine, PRM) is used in fruit packing
      plants to control fungal infections and diseases. The effluents greatly polluted
      with this fungicide, as a point source contamination, need to be technologically
      treated for their regeneration before they reach water bodies. This work
      evaluates the use of organo-montmorillonites, synthetized in our laboratory, for
      their application in adsorption and coagulation/flocculation processes for the
      removal of PRM from water. The adsorption-desorption performance of PRM in a raw
      montmorillonite (Mt) and several organo-montmorillonites (organo-Mt) obtained by
      different amounts and types of exchanged surfactants (octadecyltrimethylammonium
      (ODTMA) and didodecyldimethylammonium (DDAB) bromides and benzyltrimethylammonium
      chloride (BTMA)) was studied. The PRM adsorption on raw Mt was assigned mainly to
      an interlayer occupancy, while hydrophobic interactions between PRM and the
      surfactants in the exchanged samples increased PRM adsorption, which was
      correlated with the surfactant loading. PRM desorption showed irreversible
      behavior in raw Mt, which changed to reversible for organo-Mt samples, and was
      also correlated with the increase of surfactant loading.Two of the organo-Mt with
      high surfactant loading (twice the CEC) were assayed for the removal of
      commercial PRM in coagulation/flocculation tests, and their performance was
      compared to that of the native clay (Mt). The use of the organo-Mt produced
      flocculation at a very low ratio (0.5 g L-1), whereas no flocculation was
      observed with Mt. These results proved the feasibility of the use of organo-Mt
      for the treatment of wastewater contaminated with PRM using a low organo
      Mt/liquid ratio.

PMID- 28444566
TI  - Improvement of rice seedling growth and nitrogen use efficiency by seed
      inoculation with endophytic denitrifiers.
AB  - The aim of the present study is to investigate the effect of seed inoculation
      with endophytic denitrifiers on rice seedling growth and nitrogen use efficiency
      under low- and high-urea conditions. Pseudomonas sp. B2, Streptomyces sp. A9, and
      Fusarium sp. F3 were isolated from rice plant tissues. Rice seeds inoculated with
      the denitrifiers were sown in soil fertilized with 100 and 300 mg/kg urea
      concentrations, respectively. The denitrifiers increased soil ammonia
      concentrations or kept high ammonia concentration for a longer time in soils.
      However, soil nitrate concentrations with the denitrifier treatments were lower
      than that of the control. All the denitrifier treatments increased the
      chlorophyll content by more than 200% under the low urea condition. Compared to
      the control, the denitrifier inoculation treatments significantly increased shoot
      length, fresh weight, and dry weight of rice seedlings under the low- and high
      urea conditions (P < 0.05). The chlorophyll concentrations, shoot length, wet
      weight, and dry weight of all the denitrifier treatments under the low urea
      fertilization were significantly higher than those of the control under the high
      urea fertilization (P < 0.05). The nitrogen use efficiency of rice seedlings
      might be attributable to nitrate reductases of the denitrifiers, acting as the
      rice nitrate reductase. The treatment of endophytic denitrifiers significantly
      improved rice seedling growth and nitrogen use efficiency under both low- and
      high-urea conditions.

PMID- 28444567
TI  - The behavior of antibiotic resistance genes and arsenic influenced by biochar
      during different manure composting.
AB  - The effect of two different biochar types, rice straw biochar (RSB) and mushroom
      biochar (MB), on chicken manure composting was previously examined by monitoring
      the fate of antibiotic resistance genes (ARGs) and arsenic. The behavior of ARGs
      and arsenic in other kinds of manure composting with the same biochar types had
      not been examined. In this study, we added either RSB or MB to pig and duck
      manure composts to study the behavior of ARGs (tet genes, sul genes, and
      chloramphenicol resistance genes) and arsenic under the same experimental
      condition. The results showed that the average removal values of selected ARGs
      were respectively 2.56 and 2.09 log units in duck and pig manure compost without
      the addition of biochar. The effect of biochar addition on the average removal
      value of ARGs depended on the type of biochar and manure. For instance, in pig
      manure compost, MB addition increased the average removal value of ARGs, while
      RSB addition decreased. And both biochar additions had a negative influence on
      the average removal value of ARGs in duck manure compost. Analytical results also
      demonstrated that MB addition reduced total arsenic and the percentage of
      bioavailable arsenic more than RSB.

PMID- 28444568
TI  - Effect of phosphorus addition on the reductive transformation of
      pentachlorophenol (PCP) and iron reduction with microorganism involvement.
AB  - The transformation of phosphorus added to the soil environment has been proven to
      be influenced by the Fe biochemical process, which thereby may affect the
      transformation of organic chlorinated contaminants. However, the amount of
      related literatures regarding this topic is limited. This study aimed to
      determine the effects of phosphorus addition on pentachlorophenol (PCP) anaerobic
      transformation, iron reduction, and paddy soil microbial community structure.
      Results showed that the transformation of phosphorus, iron, and PCP were closely
      related to the microorganisms. Moreover, phosphorus addition significantly
      influenced PCP transformation and iron reduction, which promoted and inhibited
      these processes at low and high concentrations, respectively. Both the maximum
      reaction rate of PCP transformation and the maximum Fe(II) amount produced were
      obtained at 1 mmol/L phosphorus concentration. Among the various phosphorus
      species, dissolved P and NaOH-P considerably changed, whereas only slight changes
      were observed for the remaining phosphorus species. Microbial community structure
      analysis demonstrated that adding low concentration of phosphorus promoted the
      growth of Clostridium bowmanii, Clostridium hungatei, and Clostridium intestinale
      and Pseudomonas veronii. By contrast, high-concentration phosphorus inhibited
      growth of these microorganisms, similar to the curves of PCP transformation and
      iron reduction. These observations indicated that Clostridium and P. veronii,
      especially Clostridium, played a vital role in the transformation of related
      substances in the system. All these findings may serve as a reference for the
      complicated reactions among the multiple components of soils.

PMID- 28444569
TI  - A New Science Publishing System for a Budding Science Publishing Crisis.
AB  - The current science publishing system is in need of a positive transformation for
      the good of scientists and society as a whole. Herein, we propose features that,
      in our view, will distinguish the science publishing system of the future.

PMID- 28444571
TI  - ?

PMID- 28444570
TI  - Current MitraClip experience, safety and feasibility in the Netherlands.
AB  - PURPOSE: Data on MitraClip procedural safety and efficacy in the Netherlands are
      scarce. We aim to provide an overview of the Dutch MitraClip experience. METHODS:
      We pooled anonymised demographic and procedural data of 1151 consecutive
      MitraClip patients, from 13 Dutch hospitals. Data was collected by product
      specialists in collaboration with local operators. Effect on mitral regurgitation
      was intra-procedurally assessed by transoesophageal echocardiography. Technical
      success and device success were defined according to modified definitions of the
      Mitral Valve Academic Research Consortium (MVARC). RESULTS: Median age was 76
      (interquartile range 69-82) years and 59% were males. Patients presented with
      >=moderate mitral regurgitation and a predominance of functional mitral
      regurgitation (72%). Overall, 611 (53%) patients were treated with one Clip, 486
      (42%) with >=2 Clips and 54 (5%) received no Clip. The number of patients with
      >=2 Clips increased from 22% in 2009 to 52% in 2016. Device success and technical
      success were 91 and 95%, respectively, and were consistent over the years.
      Significant reduction of mitral regurgitation by MitraClip was achieved in 94% of
      patients and was observed more often in patients with functional mitral
      regurgitation (95% vs. 91%, p = 0.025). Device time declined from 145 min in 2009
      to 55 min in 2016. CONCLUSION: MitraClip experience in the Netherlands is growing
      with excellent technical success and device success. Over the years, device time
      decreased and more patients were treated with >=2 Clips.

PMID- 28444572
TI  - National health insurance subscription and maternal healthcare utilisation across
      mothers' wealth status in Ghana.
AB  - INTRODUCTION: This study is against the backdrop that despite the forty-nine
      percent decline in Maternal Mortality Rate in Ghana, the situation still remains
      high averaging 319 per 100,000 live births between 2011 and 2015. OBJECTIVE: To
      examine the relationship between National Health Insurance and maternal
      healthcare utilisation across three main wealth quintiles (Poor, Middle and
      Rich). METHODS: The study employed data from the 2014 Ghana Demographic and
      Health Survey. Both descriptive analysis and binary logistic regression were
      conducted. RESULTS: Descriptively, rich women had high antenatal attendance and
      health facility deliveries represented by 96.5% and 95.6% respectively. However,
      the binary logistic regression results revealed that poor women owning NHIS are
      7% (CI = 1.76-2.87) more likely to make at least four antenatal care visits
      compared to women in the middle wealth quintile (5%, CI = 2.12-4.76) and rich
      women (2%, CI = 1.14-4.14). Similarly, poor women who owned the NHIS are 14% (CI
      = 1.42-2.13) likely to deliver in health facility than women in the middle and
      rich wealth quintile. CONCLUSION: The study has vindicated the claim that NHIS
      Scheme is pro-poor in Ghana. The Ministry of Health should target women in the
      rural area to be enrolled on the NHIS to improve maternal healthcare utilisation
      since poverty is principally a rural phenomenon in Ghana.

PMID- 28444574
TI  - A Randomized, Controlled Trial of the Effectiveness of a Psychoeducational
      Intervention on Family Caregivers of Patients with Mental Disorders.
AB  - The present study aimed to investigate the effectiveness of a psychoeducational
      intervention on caregivers of patients assisted by the Center for Psychosocial
      Health Care (CPHC) focusing on the patient's psychopathology. This was a
      randomized clinical trial with 130 caregivers with higher mean burden scores
      assessed using the Zarit Burden Interview Scale (ZBI) (66 caregivers in the
      intervention group and 64 in the control group). The intervention included six
      home visits of psychoeducational interventions according to each mental disorder
      identified in the CPHC records. The intervention group had a reduction of 4.8
      points in ZBI mean score (p = 0.008) and in the control group, the reduction was
      1.9 points, which was not significant (p = 0.305). It is possible to think that
      psychoeducation may have served to inform about the disease and how to deal with
      it, to give emotional support to caregivers and to implement coping strategies
      and stress management.

PMID- 28444573
TI  - The Effect of Different Types of Nanoparticles on FUS and TDP-43 Solubility and
      Subcellular Localization.
AB  - Increased environmental pollution has been suggested as one of the possible
      causes for increased incidence of neurodegenerative and developmental disorders.
      Through the environmental pollution, everyday consumer products and nanomedical
      applications, we are also exposed to various nanoparticles (NPs). Specific types
      of NPs have been shown to be able to cause neural damage in vivo through
      processes such as disruption of the blood-brain barrier, induction of
      neuroinflammation, increase in oxidative stress and protein aggregation. In this
      study, we analysed the influence of PEI-coated magnetic NPs designed for
      biotechnological applications and industrial SiO2, TiO2 N and TiO2 P25 NPs on
      intracellular localization and solubility of fused in farcoma (FUS) and TAR-DNA
      binding protein 43 (TDP-43) that are important pathological hallmarks of
      amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).
      SH-SY5Y neuroblastoma cells and B16 mouse melanoma cells were exposed to NPs for
      24 h and analysed using confocal microscopy and Western blot. Exposure to 50
      MUg/ml TiO2 N and 4 MUg/ml PEI NPs in SH-SY5Y cells caused cell toxicity-induced
      changes in expression in different biochemical/cellular fractions for both FUS
      and TDP-43 proteins. TiO2 N induced a drop in nuclear levels of TDP-43 and
      increase in cytoplasmic levels of FUS, while PEI NPs increased nuclear levels of
      FUS. Furthermore, TiO2 N and PEI induced a reduction of FUS and TDP-43 quantity
      in the less soluble urea fraction. No formation of stress granules was observed.
      These results demonstrate that TiO2 N and PEI NPs can affect the behaviour of FUS
      and TDP-43 proteins; however, the changes were relatively minor compared to
      pathological changes even for the high NP concentrations (50 MUg/ml) used in this
      study.

PMID- 28444575
TI  - Erratum to: Prevalence and characterization of non-sicca onset primary Sjogren
      syndrome with interstitial lung involvement.

PMID- 28444576
TI  - Expression of CCR6 on B cells in systemic lupus erythematosus patients.
AB  - B cells are known to play a dominant pathogenic role in autoimmune conditions
      such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. In recent
      times, the chemokine receptor CCR6 and its cognate ligand CCL20 have been shown
      to play a role in the fundamental kinetics of germinal centres and B cell
      responses. As CCR6 is found on B cells and is upregulated after activation, we
      investigated the expression of CCR6 on naive, pre-germinal centre (GC), GC/plasma
      cell and memory B cells in peripheral B cells of SLE patients and healthy
      controls using flow cytometry. Pre-germinal centre B cells are found in lower
      proportions and the expression of CCR6 is increased on B cells of SLE patients,
      suggesting a role for the chemokine pair in the pathogenesis of the disease.
      Further studies are needed to explore these preliminary results.

PMID- 28444577
TI  - Comparison of clinical, serological, and prognostic differences among juvenile-,
      adult-, and late-onset lupus nephritis in Korean patients.
AB  - We investigated whether lupus nephritis (LN) patients could be distinguished
      based on the time of disease onset and, if so, whether the groups differed in
      their clinical and laboratory features and long-term prognosis in ethnically
      homogeneous Korean patients. We enrolled 117 systemic lupus erythematosus
      patients with available clinical data at the time of renal biopsy of LN.
      Sociodemographic, clinical, and laboratory data and concomitant diseases were
      evaluated at the time of renal biopsy. We divided LN patients, according to age
      at LN diagnosis, into three groups: juvenile-onset LN (JLN, diagnosed at <=18
      years), adult-onset LN (ALN, diagnosed at 18-50 years), and late-onset LN (LLN,
      diagnosed at >50 years) and compared demographic, clinical, histological, and
      laboratory findings. We also compared treatment and long-term prognosis of LN. Of
      the 117 LN patients, 20 (17.8%), 84 (71.3%), and 13 (10.9%) were JLN, ALN, and
      LLN patients, respectively. LLN patients showed higher white blood cell counts
      and lower estimated glomerular filtration rate than ALN or LLN patients. LLN
      patients had higher chronicity indices and scores. Anti-Ro antibodies were found
      more frequently in ALN patients, and lower complement levels were more common in
      JLN patients. During a mean follow-up of 76.5 months, development of chronic
      kidney disease and death were higher in LLN patients than in JLN and ALN
      patients. LLN patients showed higher chronicity indices and deterioration of
      kidney function and death in long-term follow-up compared with JLN and ALN
      patients. Therefore, LLN patients should be carefully monitored to avoid poor
      outcomes.

PMID- 28444578
TI  - Experimental Psychosis Research and Schizophrenia-Similarities and
      Dissimilarities in Psychopathology.
AB  - The aim of experimental psychopathology is to delineate overlapping functional
      disorders of psychoneurobiologically-defined systems where a set of common
      symptoms may correspond to a variety of nosological entities. According to the
      vulnerability model of psychosis, experimental research needs to go beyond
      categories such as "schizophrenia". Prospective studies of the effects of
      psychoactive substances in normal control subjects offer several methodological
      advantages over routine clinical reviews of schizophrenic patients, especially in
      terms of standardization. Carefully designed studies utilizing a model psychosis
      paradigm are a step toward symptom-oriented research. Combining psychological and
      neurobiological techniques, the experimental psychopathological approach can
      provide us with a valuable tool for psychiatric research.

PMID- 28444579
TI  - The Gut, Its Microbiome, and Hypertension.
AB  - PURPOSE OF THE REVIEW: Evidence is rapidly accumulating implicating gut dysbiosis
      in hypertension (HTN). However, we are far from understanding whether this is a
      cause or consequence of HTN, and how to best translate this fundamental knowledge
      to advance the management of HTN. This review aims to summarize recent advances
      in the field, illustrate the connections between the gut and hypertension, and
      establish that the gut microbiota (GM)-gut interaction is centrally positioned
      for consideration as an innovative approach for HTN therapeutics. RECENT
      FINDINGS: Animal models of HTN have shown that gut pathology occurs in HTN, and
      provides some clues to mechanisms linking the dysbiosis, gut pathology, and HTN.
      Circumstantial evidence links gut dysbiosis and HTN. Gut pathology, apparent in
      animal HTN models, has not been fully investigated in hypertensive patients.
      Objective evidence and an understanding of mechanisms could have a major impact
      for new antihypertensive therapies and/or improved applications of current ones.

PMID- 28444580
TI  - Three-dimensional virtual planning of corrective osteotomies of distal radius
      malunions: a systematic review and meta-analysis.
AB  - The purpose of this study was to summarize and evaluate results of three
      dimensional (3D-) planned corrective osteotomies of malunited distal radius
      fractures. 3D-planning techniques provide the possibility to address 3D-deformity
      that conventional planning methods might not address. We systematically searched
      PubMed, EMBASE and the Cochrane library for studies that performed a 3D-planned
      corrective osteotomy on patients with a malunited distal radius fracture. Fifteen
      studies with a total of 68 patients were included in the analysis. In 96% of
      cases, the preoperatively present palmar tilt, radial inclination and ulnar
      variance showed statistically significant improvement postoperatively with
      restoration to within 5 degrees  or 2 mm of their normal values. Mean flexion
      extension, pro-supination and grip strength showed statistically significant
      improvement (p < 0.05). Complications were reported in 11 out of 68 patients
      (16%). With the current advances in 3D printing technology, 3D-planned corrective
      osteotomies seem a promising technique in the treatment of complex distal radius
      malunions. Level of evidence IV Systematic review of case series, Level IV.

PMID- 28444581
TI  - CORR Insights(r): Hamstring Autograft versus Patellar Tendon Autograft for ACL
      Reconstruction: Is There a Difference in Graft Failure Rate? A Meta-analysis of
      47,613 Patients.

PMID- 28444582
TI  - CORR Insights(r): Hyaluronic Acid-based Hydrogel Coating Does Not Affect Bone
      Apposition at the Implant Surface in a Rabbit Model.

PMID- 28444583
TI  - Editorial Comment: 2016 Musculoskeletal Infection Society Proceedings.

PMID- 28444584
TI  - CORR Insights(r): Single-stage Acetabular Revision During Two-stage THA Revision
      for Infection is Effective in Selected Patients.

PMID- 28444585
TI  - CORR Insights(r): Prediction of Polyethylene Wear Rates from Gait Biomechanics
      and Implant Positioning in Total Hip Replacement.

PMID- 28444586
TI  - Cereal phytases and their importance in improvement of micronutrients
      bioavailability.
AB  - Phytic acid is a main reservoir of phosphorous (P) in plants and contributes to
      about 80% of the total P in cereal seeds. However, it is well known to possess
      anti-nutritional behavior. Because it has strong affinity to chelate divalent
      ions e.g. calcium, magnesium, and especially with iron and zinc. Therefore, it is
      extremely poor as a dietary source of P. To enhance bio-availability of
      micronutrients, an enzyme namely phytase is known to hydrolyze phytic acid.
      Unfortunately, phytase is not produced in the stomach of monogastric animals and
      humans. Thus, the presence of phytic acid in cereal foods has become major
      concern about the deficiency of essential micronutrients in developing countries.
      To address this problem, various types of phytase have been isolated, purified
      and characterized from different varieties of cereal till date. Therefore, the
      present article discusses about catalytic properties, gene regulation of such
      cereal phytases and their importance in ensuring food safety.

PMID- 28444587
TI  - Solid state fermentation (SSF): diversity of applications to valorize waste and
      biomass.
AB  - Solid state fermentation is currently used in a range of applications including
      classical applications, such as enzyme or antibiotic production, recently
      developed products, such as bioactive compounds and organic acids, new trends
      regarding bioethanol and biodiesel as sources of alternative energy, and
      biosurfactant molecules with environmental purposes of valorising unexploited
      biomass. This work summarizes the diversity of applications of solid state
      fermentation to valorize biomass regarding alternative energy and environmental
      purposes. The success of applying solid state fermentation to a specific process
      is affected by the nature of specific microorganisms and substrates. An
      exhaustive number of microorganisms able to grow in a solid matrix are presented,
      including fungus such as Aspergillus or Penicillum for antibiotics, Rhizopus for
      bioactive compounds, Mortierella for biodiesel to bacteria, Bacillus for
      biosurfactant production, or yeast for bioethanol.

PMID- 28444588
TI  - Unveiling differentially expressed genes upon regulation of transcription factors
      in sepsis.
AB  - In this study, we integrated the gene expression data of sepsis to reveal more
      precise genome-wide expression signature to shed light on the pathological
      mechanism of sepsis. Differentially expressed genes via integrating five
      microarray datasets from the Gene Expression Omnibus database were obtained. The
      gene function and involved pathways of differentially expressed genes (DEGs) were
      detected by GeneCodis3. Transcription factors (TFs) targeting top 20 dysregulated
      DEGs (including up- and downregulated genes) were found based on the TRANSFAC. A
      total of 1339 DEGs were detected including 788 upregulated and 551 downregulated
      genes. These genes were mostly involved in DNA-dependent transcription
      regulation, blood coagulation, and innate immune response, pathogenic escherichia
      coli infection, epithelial cell signaling in helicobacter pylori infection, and
      chemokine signaling pathway. TFs bioinformatic analysis of 20 DEGs generated 374
      pairs of TF-target gene involving 47 TFs. At last, we found that five top ten
      upregulated DEGs (S100A8, S100A9, S100A12, PGLYRP1 and MMP9) and three
      downregulated DEGs (ZNF84, CYB561A3 and BST1) were under the regulation of three
      hub TFs of Pax-4, POU2F1, and Nkx2-5. The identified eight DEGs may be regarded
      as the diagnosis marker and drug target for sepsis.

PMID- 28444589
TI  - Ripening improves the content of carotenoid, alpha-tocopherol, and
      polyunsaturated fatty acids in tomato (Solanum lycopersicum L.) fruits.
AB  - The tomato fruits during different stages of ripening have been extensively
      characterized for nutritionally important bioactives; however, changes in fatty
      acid composition are not available. Thus, in the present study, changes in fatty
      acid, along with carotenoid and alpha-tocopherol, were studied during the six
      stages of ripening. Fruits were harvested at the green, breaker, turning, pink,
      light red, and red stages, which occurred at means of 30, 35, 40, 46, 50, and 55
      days after anthesis (DAE), respectively. During the ripening process, profiles of
      all the metabolites altered significantly (p < 0.05). All-E-lycopene content
      increased from the breaker (0.21 MUg/g FW) to the red stage (30.6 MUg/g FW),
      while all-E-lutein was slightly increased during initial stages of ripening and
      then decreased significantly, with the highest (4.15 MUg/g FW) in the fruits of
      the pink stage. Furthermore, the contents of alpha-tocopherol increased during
      ripening, and its increase was highest between light red to the red stages. In
      all the ripening stages, linoleic acid (C18:2n6c) was found in the highest
      quantity (42.3-49.2%), followed by oleic (C18:1n9c; 20.1-26.6%) and palmitic
      acids (C16:0; 16.6-17.7%). With fruit ripening, the ratio of polyunsaturated
      fatty acids and saturated fatty acids (PUFAs:SFAs) was increased significantly
      from 1.89 (green) to 2.19 (red). Interestingly, the oleic acid proportions
      correlated inversely with linoleic (r = -0.450) and alpha-linolenic acid (r = 
      0.904), during all the stages of ripening. The highest and lowest contents of
      oleic acid and linoleic acid (26.7 and 42.3%, respectively) were recorded in the
      fruits of stage 3 (turning). In conclusion, ripening in tomatoes is accompanied
      by significant increases in carotenoids and alpha-tocopherol, as well as by
      concomitant increases in PUFAs.

PMID- 28444590
TI  - Transcripts of pectin-degrading enzymes and isolation of complete cDNA sequence
      of a pectate lyase gene induced by coffee white stem borer (Xylotrechus
      quadripes) in the bark tissue of Coffea canephora (robusta coffee).
AB  - Of the two commercially cultivated coffee (Coffea) species, C. arabica (arabica)
      is highly susceptible and C. canephora (robusta) is highly resistant to the
      insect pest Xylotrechus quadripes (Coleoptera: Cerambycidae), commonly known as
      coffee white stem borer (CWSB). We constructed a forward-subtracted cDNA library
      by Suppression Subtractive Hybridization (SSH) from robusta bark tissue for
      profiling genes induced by CWSB infestation. Among the 265 unigenes of the SSH
      EST library, 7 unigenes (5 contigs and 2 singletons) matching different pectin
      degrading enzymes were discovered. These ESTs matched one pectate lyase, three
      polygalacturonases, and one pectin acetylesterase gene. Quantitative real-time
      PCR (qRT-PCR) revealed that CWSB infestation strongly induces the pectate lyase
      gene at 72 h. Complete cDNA sequence of the pectate lyase gene was obtained
      through 3' and 5' RACE reactions. It was a 1595 bp long sequence that included
      full CDS and both UTRs. Against C. canephora genome sequences in Coffee Genome
      Hub database ( http://coffee-genome.org/ ), it had 22 matches to different
      pectate lyase genes mapped on 9 of the 11 pseudochromosomes, the top match being
      Cc07_g00190 Pectate lyase. In NCBI database, it matched pectate lyase sequences
      of several plants. Apart from C. canephora, the closest pectate lyase matches
      were from Sesamum indicum and Nicotiana tabacum. The pectinolytic enzymes
      discovered here are thought to play a role in the production of
      oligogalacturonides (OGs) which act as Damage-Associated Molecular Pattern (DAMP)
      signals eliciting innate immunity in plants. The pectate lyase gene, induced by
      CWSB infestation, along with other endogenous pectinolytic enzymes and CWSB
      specific elicitors, may be involved in triggering basal defense responses to
      protect the CWSB-damaged tissue against pathogens, as well as to contain CWSB in
      robusta.

PMID- 28444591
TI  - Biotechnological application of sustainable biogas production through dry
      anaerobic digestion of Napier grass.
AB  - Napier grass (Pennisetum purpureum), represents an interesting substrate for
      biogas production. The research project evaluated biogas potential production
      from dry anaerobic digestion of Napier grass using batch experiment. To enhance
      the biogas production from ensiled Napier grass, thermal and alkaline pre
      treatments were performed in batch mode. Alkali hydrolysis of Napier grass was
      performed prior to batch dry anaerobic digestion at three different mild
      concentrations of sodium hydroxide (NaOH). The study results confirmed that NaOH
      pretreated sample produced high yield of biogas than untreated (raw) and hot
      water pretreated samples. Napier grass was used as the mono-substrate. The biogas
      composition of carbon dioxide (30.10%), methane (63.50%) and 5 ppm of H2S was
      estimated from the biogas. Therefore, fast-growing, high-yielding and organic
      matter-enriched of Napier grass was promising energy crop for biogas production.

PMID- 28444592
TI  - Molecular characterization of phytoplasma of 16SrI-B group association with
      Acalypha indica in India.
AB  - The typical phytoplasma symptoms of little leaf, yellowing, chlorosis, witches'
      broom, and stunting growth were observed on Acalypha indica plants during the
      field survey conducted at Lucknow and surrounding districts in year 2015-2016. To
      confirm the association and possibility of phytoplasma etiology, PCR assays were
      performed using universal primer pairs (P1/P6) and nested primer pairs
      (R16F2n/R2) in a total of five diseased samples along with control. A ~1.2 Kb
      amplicon was observed in nested PCR assay in diseased sample; however, no band
      was observed in control sample. The positive amplicons were sequenced for 16S
      rDNA and used for the virtual RFLP analysis and phylogenetic studies. BLASTn
      search showed 99-100% sequence identities with the 'Candidatus phytoplasma
      asteris' members (16SrI group) and phylogenetic analysis showed closest
      relationship with member of 16SrI group. The virtual RFLP assigned it as a member
      of 16SrI-B subgroup. This is the first record of phytoplasma association of 'Ca.
      P. asteris' subgroup B with A. indica in the world.

PMID- 28444593
TI  - Decolourization and biodegradation of Navy blue HER (Reactive Blue 171) dye from
      Marasmius sp. BBKAV79.
AB  - White rot fungus Marasmius sp. BBKAV79 (GenBank accession number-KP455496,
      KP455497) exhibited decolourization and degradation of Navy blue HER dye
      (concentration 50 mg l-l) within 24 h under shaking condition. In the present
      study, various investigated parameters like initial dye concentration, pH,
      temperature, carbon and nitrogen sources were optimized to develop a faster
      decolourization process by Marasmius sp. BBKAV79. High-performance liquid
      chromatography, Fourier transform infrared spectroscopy and gas chromatography
      and mass spectroscopy analysis of the extracted product confirmed the
      biodegradation of Navy blue HER. The microbial toxicity and phytotoxicity assay
      revealed that the degradation of Navy blue HER produced nontoxic metabolites.

PMID- 28444594
TI  - Bio-transformation and stabilization of arsenic (As) in contaminated soil using
      arsenic oxidizing bacteria and FeCl3 amendment.
AB  - A combination of biological and chemical methods was applied in the present study
      to evaluate the removal of arsenic (As) from contaminated soil. The treatment
      involved As-oxidizing microbes aimed of transforming the more toxic As (III) to
      less toxic As (V) in the soil. FeCl3 was added at three different concentrations
      (1, 2, and 3%) to stabilize the As (V). Leaching of the treated soil was
      investigated by making a soil column and passing tap water through it to
      determine solubility. Experimental results indicated that the bacterial activity
      had a pronounced positive effect on the transformation of As, and decreased the
      soluble exchangeable fraction from 50 to 0.7 mg/kg as compared to control and
      from 50 to 44 mg/kg after 7 days of treatment. FeCl3 also played an indispensable
      role in the adsorption/stabilization of As in the soil; 1 and 2% FeCl3 strongly
      influenced the adsorption of As (V). The soil leachate contained negligible
      amount of As and trace metals, which indicates that combining an efficient
      microbe with a chemical treatment is very effective route for the removal and
      stabilization of As from contaminated soil in the environment.

PMID- 28444595
TI  - Cloning and characterization of auxin efflux carrier genes EcPIN1a and EcPIN1b
      from finger millet Eleusine coracana L.
AB  - Auxin signaling events in plants play important role in developmental regulation
      as well as gravitropic responses and plays crucial role in the development of
      root, lateral root and root hairs. The gene that is known to be most important in
      the development of root, lateral root and root hairs is commonly known as auxin
      efflux carrier (PIN). Being commonly known as orphan plant, the genome sequence
      of Eleusine coracana is not known yet, and hence it was very difficult to conduct
      advanced research in root development in this plant. As PIN gene plays crucial
      role in root development, to have some advanced study we proposed to clone the
      PIN genes from E. coracana. We cloned two PIN genes in E. coracana and named them
      as EcPIN1a and EcPIN1b. The coding sequence (CDS) of EcPIN1a was 1779 bp and
      EcPIN1b was 1788 bp long that encodes for 593 and 596 amino acids, respectively.
      In-silico analysis shows the presence of transmembrane domain in EcPIN1a and
      EcPIN1b protein. Multiple sequence alignment of EcPIN1a and EcPIN1b protein shows
      the presence of several conserved motifs. Phylogenetic analysis of EcPIN1a and
      EcPIN1b grouped with the PIN gene of monocot plant Oryza sativa. This shows that
      EcPIN genes were monocot specific, and closely match with the PIN genes of O.
      sativa. The transcript analysis of EcPIN1a gene in leaf tissue shows gradual up
      regulation from 7th to 28th days of developmental time period while the
      transcript level was found to be lower in root tissue. The transcript abundance
      of EcPIN1b was not detected. Gradual up-regulation of EcPIN1a gene in
      developmental stages signifies its important role in root development in E.
      coracana.

PMID- 28444596
TI  - Response surface design for accumulation of selenium by different lactic acid
      bacteria.
AB  - The accumulation of selenium (Se) by Lactobacillus delbrueckii ssp. bulgaricus
      (Lb) and Streptococcus thermophilus (St) at the different cultivation conditions,
      including initial pH, inoculum dose (%), and temperature ( degrees C), was
      investigated in this work. Se enrichment efficiency was optimized using the
      Design-Expert software for response surface methodology on a basis of single
      factor experiment. The antioxidant activities of Se-enriched Lactic acid bacteria
      (LAB) were also investigated. The qualitative analysis of Se-enriched LAB was
      performed by FT-IR spectra. The cell morphology and chemical element components
      were measured by a scanning electron microscope (SEM) equipped with energy
      dispersive X-ray spectroscopy. The results indicated that the optimum initial pH,
      inoculum doses, and temperatures of Lb and St were 5.96, 6.73%, 33.24  degrees C,
      and 6.37, 6%, 40  degrees C, respectively. Under the optimal conditions, the
      ratios of Se enrichment reached 94.34% for Lb and 97.05% for St. Furthermore, Se
      enriched LAB enhanced scavenging rates on DPPH, ABTS free radical, and also
      heightened reducing activity. The FT-IR results showed that the two Se-enriched
      strains had similar characteristic absorption peaks, which were further
      demonstrated that both Se biomasses had the same carbonyl, carboxyl, and hydroxyl
      groups. Elemental selenium nanoparticles were verified around cell surfaces of Se
      enriched LAB, which implied that both strains had detoxification ability when
      grown in liquid media containing selenite.

PMID- 28444597
TI  - Biodegradation of pyrene and benzo[a]pyrene in the liquid matrix and soil by a
      newly identified Raoultella planticola strain.
AB  - In the current study, the PL7 strain was isolated from soil and identified as
      Raoultella planticola based on its physiological characteristics and 16S rDNA
      sequence. By the 10th day, the PL7 strain degraded 52.0% of the pyrene (PYR)
      content and 50.8% of the benzo[a]pyrene (BaP) content in 20 mg L-1 PYR and 10 mg
      L-1 BaP in the liquid matrix. The half-life of PYR and BaP by PL7 degradation was
      8.59 and 9.46 days, respectively. At pH 8.0, the degradation rates of PYR and BaP
      by PL7 were significantly higher at 30  degrees C than at 20 and 40  degrees C.
      The degradation ability of PL7 differed in red soil, paddy soil and fluvo-aquic
      soil; red soil produced the fastest degradation rates. The half-life of PYR and
      BaP by PL7 degradation in red soil was 21.7 and 11.9 days, respectively; however,
      without PL7 the half-life of PYR in red soil was 91.2 days. This study
      demonstrated the significant potential of the PL7 strain for bioremediation
      applications in the liquid matrix and soil contaminated by PAHs.

PMID- 28444599
TI  - Study of enzymatic saccharification of Agave leaves biomass to yield fermentable
      sugars.
AB  - Agave is a good source of polysaccharides for the production of fermentable
      sugars as sustainable bioenergy feedstock solutions for semi-arid and arid lands.
      This plant grows in arid areas, which correspond to a large territory in northern
      Mexico. Having lignocellulose as the polysaccharide of interest, the information
      for the enzymatic saccharification of this kind of material is limited. Agave
      cell walls have a unique recalcitrant nature, but having a high cellulose
      content, makes this plant material an interesting research subject. In this work,
      acidic, alkaline and aqueous pretreatments were evaluated to generate a biomass
      rich in cellulose. The saccharification of pretreated Agave leaves-residue was
      evaluated under experimental designs to identify the most suitable conditions for
      enzymatic hydrolysis. Maximum value obtained was 31% glucose, which further
      increased to 41.4% at extended hydrolysis time of 96 h. The highest cellulose
      saccharification reached was up to 61.81%, making Agave atrovirens an alternative
      for bioethanol production in its geographical area of cultivation.

PMID- 28444598
TI  - Synergistic effect of thermostable beta-glucosidase TN0602 and cellulase on
      cellulose hydrolysis.
AB  - Thermophilic enzymes have many potential benefits in industrial production with
      increased flexibility related to process configurations. A thermostable beta
      glucosidase from Thermotoga naphthophila RUK-10 was found to possess catalytic
      activity for cellobiose hydrolysis with a high potential for application in
      biomass conversion. The aggregation of cellobiose often has an inhibitory effect
      on cellobiohydrolases and endoglucanases during cellulose hydrolysis. The
      presence of beta-glucosidases has a significant effect on reducing inhibition
      from hydrolytic products by hydrolysing the intermedia cellobiose. In this study,
      beta-glucosidase TN0602 exhibited a high tolerance to glucose and high
      thermostability even after a long incubation (>72 h). Additionally, supplementing
      beta-glucosidase TN0602 with microcrystalline cellulose, untreated corn straw and
      steam-exploded corn straw hydrolysis reactions containing a commercial cellulase
      led to an increased conversion rate in released glucose compared to hydrolysis
      without the addition of beta-glucosidase (15.82, 30.62 and 35.21%, respectively);
      the increase of conversion rates were 61.86, 93.50 and 94.55%. It was thus shown
      that an obvious synergistic effect exists between TN0602 and cellulases for
      cellulose hydrolysis, suggesting its potential as a component of enzymatic
      cocktails for the conversion of lignocellulosic biomass to other chemicals.

PMID- 28444600
TI  - Antibiotic sensitivity pattern of indigenous lactobacilli isolated from curd and
      human milk samples.
AB  - The gut microbiota plays a vital role in host well-being and lactic acid bacteria
      (LAB) have gained an overwhelming attention as health promoter. This perception
      has evolved from traditional dairy products to a money-spinning market of
      probiotics. The safety of probiotics is coupled to their intended use and LAB may
      act as pool of antimicrobial resistance genes that could be transferred to
      pathogens, either in food matrix or in gastrointestinal tract, which could be
      detrimental to host. This study evaluated the antibiotic susceptibility patterns
      of LAB isolated from curd (20) and human milk (11) samples. Antibiotic
      susceptibility was determined against 26 common antibiotics, following reference
      disc diffusion assay. A varied response in terms of susceptibility and resistance
      towards antibiotics was recorded. Among curd isolates, D7 (Lactobacillus
      plantarum) was the most resistant followed by D4, D8, D10 and D25. Among human
      milk isolates, HM-1 (L. casei) showed the highest resistance profile. All LAB
      isolates displayed high susceptibility pattern towards imipenem and meropenem. In
      general, high resistivity was exhibited by human milk isolates. The present study
      showed that antibiotic resistance is widespread among different lactobacilli,
      which may pose a food safety concern. Therefore, antibiotic sensitivity should be
      considered as a vital tool for safety assessment of probiotics.

PMID- 28444601
TI  - Somatic embryogenesis from bud and leaf explants of date palm (Phoenix
      dactylifera L.) cv. Najda.
AB  - An efficient regeneration system through somatic embryogenesis was developed for
      date palm cv. Najda. Adventitious bud and proximal leaf segments cultured on
      Murashige and Skoog (MS) medium supplemented with various combinations of auxins
      and cytokinins induced embryogenesis after at least 6 months of culture. Somatic
      embryogenesis induction seemed correlated with the type of the explant, the
      induction period and the auxin used. The highest rate of somatic embryogenesis
      (86.0%) was obtained on bud explants cultured on MS medium supplemented with 45.0
      uM 2,4-dichlorophenoxyacetic acid (2,4-D), and 4.5 uM kinetin or 4.5 uM 6
      (dimethylallylamino) purine (2iP). Whereas, low levels of embryogenesis were
      obtained on media supplemented with 1-naphthalene acetic acid (NAA) or 2
      naphthoxyacetic acid (NOA). Proximal leaf segments showed somatic embryogenesis
      only when cultured on media supplemented with 2,4-D or picloram. Statistical
      analysis revealed significant effects of explant type and plant growth regulators
      (PGRs) combination on somatic embryogenesis. Somatic embryos were germinated
      successfully on PGR-free MS medium with or without activated charcoal (50.0-60.0
      and 26.6-36.6%, respectively), and 80.0% of plantlets survived after transferring
      to a glasshouse for 6 months. Our results will be useful for large-scale
      propagation of date palm cv. Najda, characterized by high fruit quality and
      bayoud disease resistance.

PMID- 28444602
TI  - Bioactive-guided fractionation of diols from Streptomyces sp. MSL.
AB  - An actinomycete strain with a great potential to produce bioactive compounds
      isolated from a laterite soil was identified as Streptomyces sp. MSL based on 16S
      rDNA sequence analysis. Secondary metabolites produced by the strain in optimized
      nutrient broth were extracted and analyzed by chromatographic and spectroscopic
      techniques. Among the different fractions, four diols, viz., (1) (2R,3R)-2,3
      Butanediol, (2) (2R,3S)-2,3-Butanediol, (3) 2,3-dimethyl-2,3-butanediol
      (Pinacol), and (4) (3R)-1,3-Butanediol exhibited good antimicrobial activity.
      These compounds inhibited growth of both Gram-positive and Gram-negative bacteria
      as well as fungi tested. Minimum inhibitory concentration of these compounds was
      also determined against test micro-organisms in vitro. This is the first report
      on the occurrence of 2,3-dimethyl-2,3-butanediol (Pinacol) in the genus
      Streptomyces. This paper also reports the extraction, purification, and
      antimicrobial spectrum of diols fractionated from the culture filtrate of
      Streptomyces sp. MSL.

PMID- 28444603
TI  - Physiological functioning of Lagerstroemia speciosa L. under heavy roadside
      traffic: an approach to screen potential species for abatement of urban air
      pollution.
AB  - The mitigation potential of avenue tree species needs a sound understanding,
      especially for landscape planning or planting tree species on roadside,
      especially in city limits where there is huge traffic due to more number of
      vehicles. A preliminary study was conducted to investigate the impact of heavy
      traffic movement and pollution thereof on physiological functioning of
      Lagerstroemia speciosa trees planted on roadside in terms of carbon absorption,
      mitigation potential and adaptive behavior. Trees on roadside exhibited reduced
      carbon assimilation (36.7 +/- 2.4%) and transpiration rate (42.14 +/- 2.9%),
      decreased stomatal conductance (66.85 +/- 3.87%), increased stomatal resistance
      (212.2 +/- 11.25%), more leaf thickness (40.54 +/- 3.25) and water use efficiency
      (9.4 +/- 0.87%), and changes in lead (179.31 +/- 10.24%) and proline (15.61 +/-
      1.92%) concentration in leaf tissues when compared to less traffic area (FRI
      campus). The impacts were also witnessed in the form of enhanced vapour pressure
      deficit of air (63.18 +/- 4.94%) and leaf (45.72 +/- 3.25%), and air temperature
      (3.2 +/- 0.16%) and leaf temperature (9.0 +/- 0.82%) along roadside trees. It was
      inferred that heavy traffic movements interrupt the physiological functioning of
      trees due to alteration in the surrounding environment as compared to non-traffic
      areas. The present study provides baseline information to further explore and
      identify the potential avenue tree species having significant mitigation
      potential and adaptive efficiency to heavy traffic movements for improving urban
      environment.

PMID- 28444604
TI  - Effect of gamma-irradiation on fumonisin producing Fusarium associated with
      animal and poultry feed mixtures.
AB  - Contamination of animal and poultry feeds by Fusarium and the mycotoxin Fumonisin
      B1 is frequent in the feed supply chain. The present study evaluated the
      prevalence of fumonisin B1 producing Fusarium among irradiated and non-irradiated
      animal and poultry feed mixtures. Further, the efficiency of gamma-rays (2.5,
      5.0, 7.5, and 10.0 kGy) to minimize Fusarium growth and biosynthesis of fumonisin
      B1 in artificially inoculated feed was evaluated. A total of 108 feed samples
      were collected in which 45.37% of feed mixtures were contaminated with Fusarium
      species. Among the contaminated samples, the frequency levels of F.
      verticillioides and F. proliferatum were 42.59 and 24.07%, respectively. Out of
      the 98 Fusarium isolates from feed samples, 84.7% of F. verticillioides and
      64.28% of F. proliferatum were positive for FUM1 set of primers. Fumonisin B1
      biosynthesis by the FUM1 positive isolates in feed was confirmed by LC/MS which
      recorded 0.1-45 ug/g of feed. Fungal growth and viable count of Fusarium in PDA
      medium and feed decreased with increasing irradiation dosage. Interestingly,
      fumonisin content was 11 ug/g of feed in 2.5 kGy irradiated sample as compared to
      5 ug/g of feed in non-irradiated control. Ionizing radiation at 7.5 kGy was found
      lethal for fungal growth and fumonisin production. Our findings suggest that
      gamma-radiation above 7.5 kGy effectively prevented fungal growth in feed
      mixtures and minimized the exposure of animal and human life to the potential
      risk of mycotoxin. Also it is necessary to maintain proper storage system for
      feeds until consumption.

PMID- 28444605
TI  - Recent trends of modern bacterial insecticides for pest control practice in
      integrated crop management system.
AB  - Food security and safety are the major concern in ever expanding human population
      on the planet earth. Each and every year insect pests cause a serious damage in
      agricultural field that cost billions of dollars annually to farmers. The loss in
      term of productivity and high cost of chemical pesticides enhance the production
      cost. Irrespective use of chemical pesticides (such as Benzene hexachloride,
      Endosulfan, Aldicarb, and Fenobucarb) in agricultural field raised several types
      of environmental issues. Furthermore, continuous use of chemical pesticides
      creates a selective pressure which helps in emerging of resistance pest. These
      excess chemical pesticide residues also contaminate the environment including the
      soil and water. Therefore, the biological control of insect pest in the
      agricultural field gains more importance due to food safety and environment
      friendly nature. In this regard, bacterial insecticides offer better alternative
      to chemical pesticides. It not only helps to establish food security through
      fighting against insect pests but also ensure the food safety. In this review, we
      have categorized insect pests and the corresponding bacterial insecticides, and
      critically analyzed the importance and mode of action of bacterial pesticides. We
      also have summarized the use of biopesticides in integrated pest management
      system. We have tried to focus the future research area in this field for the
      upcoming scientists.

PMID- 28444606
TI  - Species evolution and quality evaluation of four Coptis herbal medicinal
      materials in Southwest China.
AB  - Coptis herbs, which are important herbal medicinal materials, are the dried
      rhizomes of various plants. In China's herbal market, drying herbs can severely
      influence morphological markers such as shape, color, and odor, which make
      consumers difficult to precisely identify the herbs and effectively evaluate the
      quality. Here, we present the phylogenetic analysis of four Coptis herbal
      medicinal materials based on internal transcribed spacer sequences. C. chinensis,
      C. omeiensis, C. deltoidea and C. teeta constituted a monophyletic group. In this
      group, C. omeiensis and C. deltoidea cluster together, and they form the sister
      group with C. teeta, and C. chinensis locate the outermost of C. omeiensis, C.
      deltoidea and C. teeta. At the same time, the HPLC-DAD method was applied to
      simultaneously analyze main alkaloids from seventeen different samples. On the
      basis of the robust phylogenetic topology, the parsimony reconstructions of six
      effective medicinal constituents were implemented to elucidate the evolutionary
      history in Coptis herbs, and thus evaluate the herbal quality. The results showed
      that C. chinensis had been considered to be the best herb, not only the high
      content in single constituent but also in total alkaloids. In addition, all the
      samples from seventeen habitats were considered as qualified herbs, and they
      could meet the requirements of national quality standards for Coptis herbs in
      China.

PMID- 28444607
TI  - The Provision of Spiritual Care in Hospices: A Study in Four Hospices in North
      Rhine-Westphalia.
AB  - This article considers the role and the practices of spiritual care in hospices.
      While spiritual care was firmly established as one of the four pillars of
      practical hospice care alongside medical, psychological and social care by Cicely
      Saunders, the importance and functions of spiritual care in daily practice remain
      arguable. When speaking about spirituality, what are we actually speaking about?
      What form do the spiritual relations take between full-time staff and volunteers
      on the one hand, and the patients and their family members on the other? These
      were central questions of a qualitative study that we carried out in four
      hospices in North Rhine-Westphalia, Germany, to explore how spiritual care is
      provided in hospices and what significance spirituality has in hospices. The
      study shows that the advantages of a broader definition of spirituality lie in
      "spiritual care" no longer being bound to one single profession, namely that of
      the chaplain. It also opens the way for nurses and volunteers-irrespective of
      their own religious beliefs-to provide spiritual end-of-life care to patients in
      hospices. If the hospice nurses and volunteers were able to mitigate the
      patients' fear not only by using medications but also in a psychosocial or
      spiritual respect, then they saw this as a successful psychological and spiritual
      guidance. The spiritual guidance is to some degree independent of religious
      belief because it refers to a "spirit" or "inner core" of human beings. But this
      guidance needs assistance from professional knowledge considering religious
      rituals if the patients are deeply rooted in a (non-Christian) religion. Here,
      the lack of knowledge could be eliminated by further education as an essential
      but not sufficient condition.

PMID- 28444608
TI  - Mechanisms Behind Religiosity and Spirituality's Effect on Mental Health, Quality
      of Life and Well-Being.
AB  - This cross-sectional study aims to evaluate the role of meaning, peace, faith and
      religiosity on mental health, quality of life (QOL) and well-being in 782 adults.
      We found associations between (a) meaning and peace with less depression and more
      QOL, (b) peace with less stress and (c) faith and religiousness with more
      psychological QOL. Meaning and peace were more strongly associated with health
      outcomes, and those with high levels of intrinsic religiosity but low levels of
      meaning/peace have worse outcomes than those with low religiousness and high
      meaning/peace. However, religious participants found great meaning and peace than
      nonreligious participants.

PMID- 28444609
TI  - Density assessment and mapping of microorganisms around a biocomposting plant in
      Sanandaj, Iran.
AB  - Exposure to microorganisms can cause various diseases or exacerbate the
      excitatory responses, inflammation, dry cough and shortness of breath, reduced
      lung function, chronic obstructive pulmonary disease, and allergic response or
      allergic immune. The aim of the present study was to investigate the density of
      microorganisms around the air of processing facilities of a biocomposting plant.
      Each experiment was carried out according to ASTM E884-82 (2001) method. The
      samples were collected from inhaled air in four locations of the plant, which had
      a high traffic of workers and employees, including screen, conveyor belt, aerated
      compost pile, and static compost pile. The sampling was repeated five times for
      each location selected. The wind speed and its direction were measured using an
      anemometer. Temperature and humidity were also recorded at the time of sampling.
      The multistage impactor used for sampling was equipped with a solidified medium
      (agar) and a pump (with a flow rate of 28.3 l/m) for passing air through the
      media. It was found that the mean density of total bacteria was >1.7 * 103 cfu/m3
      in the study area. Moreover, the mean densities of fungi, intestinal bacteria
      (Klebsiella), and Staphylococcus aureus were 5.9 * 103, 3.3 * 103, and 4.1 * 103
      cfu/m3, respectively. In conclusion, according to the findings, the density of
      bacteria and fungi per cubic meter of air in the samples collected around the
      processing facilities of the biocomposting plant in Sanandaj City was higher than
      the microbial standard for inhaled air.

PMID- 28444610
TI  - Publicly available datasets on thallium (Tl) in the environment-a comment on
      "Presence of thallium in the environment: sources of contaminations, distribution
      and monitoring methods" by Bozena Karbowska, Environ Monit Assess (2016) 188:640
      (DOI 10.1007/s10661-016-5647-y).
AB  - This comment highlights a whole series of datasets on thallium concentrations in
      the environment that were overlooked in the recent review by Karbowska,
      Environmental Monitoring and Assessment, 188, 640, 2016 in this journal.
      Geochemical surveys carried out over the last few decades all over the world at
      various scales and using different sampling media have reported the concentration
      of thallium (and dozens more elements) in tens of thousands of samples. These
      datasets provide a 'real-world' foundation upon which source apportionment
      investigations can be based, monitoring programs devised and modelling studies
      designed. Furthermore, this comment also draws attention to two global
      geochemical mapping initiatives that should be of interest to environmental
      scientists.

PMID- 28444611
TI  - Impact of collection on bark regeneration from Stryphnodendron rotundifolium
      Mart. in northeastern Brazil.
AB  - The growing commercial demand for products with medicinal use has caused
      overexploitation of several plant species worldwide. To prevent the decline of
      these populations, the collection of these resources should be done in a
      sustainable way considering the time of its replacement in natural stocks. This
      study was designed to identify the relationship between different intensities of
      extraction of bark from the trunk of Stryphnodendron rotundifolium Mart. and its
      regeneration speed. For this, we selected two areas of Cerrado in the Northeast
      of Brazil, where a monitoring experiment with duration of 24 months was
      performed. This experiment consisted in simulating different extractive damage to
      assess the regeneration of bark. In each area, we selected 20 individuals, among
      which four treatments with five repetitions were implemented. The data showed
      that in both study areas, the trees regenerated their shells faster when
      subjected to higher collection intensities. However, this regeneration was not
      related to variations in rainfall in the environment.

PMID- 28444612
TI  - WBP2NL/PAWP mRNA and protein expression in sperm cells are not related to semen
      parameters, fertilization rate, or reproductive outcome.
AB  - PURPOSE: WBP2NL/PAWP, a protein found in the post-acrosomal region of mammalian
      spermatozoa, has been proposed as a sperm-borne oocyte-activating factor (SOAF)
      contributing to Ca2+ release within the oocyte and subsequent fertilization and
      embryo development. However, its relevance as either a diagnostic or a prognostic
      marker of fertilization failure has been questioned in the recent literature. We
      analyzed WBP2NL/PAWP gene and protein expression level and localization in
      patients without previous intracytoplasmic sperm injection (ICSI) cycles in order
      to assess its association with both sperm characteristics and ability to
      fertilize. METHODS: Raw frozen-thawed semen samples from 33 couples referred for
      oocyte donation were included in the study during 2015. Relative protein
      expression versus alpha-tubulin (western blot, WB), proportion of post-acrosomal
      WBP2NL/PAWP-positive spermatozoa over the total number of sperm cells
      (immunofluorescence), and WBP2NL/PAWP gene expression (RT-qPCR) were analyzed and
      correlated with semen analysis parameters (number, motility, and morphology) and
      with reproductive outcomes. RESULTS: WBP2NL/PAWP protein was expressed in all
      samples with high variability: relative protein expression (1.77 +/- 0.8, range
      [0.4-3.7]), proportion of positive cells (49.6% +/- 16.1, range [22-89]), and
      relative gene expression (7.3 +/- 8.2). No significant correlation (R 2 < 0.1)
      was found between gene and protein expression, neither between WBP2NL/PAWP gene
      or protein expression, and fertilization rate or other reproductive outcomes
      (i.e., pregnancy). In contrast, we found significant correlation between sperm
      morphology and WBP2NL/PAWP semiquantitative analysis in WB (r = -0.42, p < 0.05)
      and for sperm motility and WBP2NL/PAWP expression in IF (r = 0.52, p < 0.05).
      CONCLUSION: Taken into account that WBP2NL/PAWP gene and protein levels and
      distribution did not correlate with fertilization rates, this study questions the
      interest of WBP2NL/PAWP protein and gene expression analysis in sperm cells as a
      prognostic factor for the outcome of ICSI cycles. Larger studies focusing on
      WBP2NL/PAWP protein and gene expression are needed in order to evaluate the role
      of WBP2NL/PAWP as a prognostic factor for ART.

PMID- 28444613
TI  - No difference in congenital anomalies prevalence irrespective of insemination
      methods and freezing procedure: cohort study over fourteen years of an ART
      population in the south of France.
AB  - PURPOSE: A retrospective cohort study was conducted to evaluate and compare the
      prevalence of congenital anomalies in babies and fetuses conceived after four
      procedures of assisted reproduction technologies (ART). METHODS: The prevalence
      of congenital anomalies was compared retrospectively between 2750 babies and
      fetuses conceived between 2001 and 2014 in vitro fertilization with standard
      insemination (IVF), IVF with intracytoplasmic sperm injection (ICSI), IVF with
      frozen embryo transfer (FET-IVF), and ICSI with frozen embryo transfer (FET
      ICSI). Congenital anomalies were described according to European Surveillance of
      Congenital Anomalies (EUROCAT) classification. The parental backgrounds, biologic
      parameters, obstetric parameters, and perinatal outcomes were compared between
      babies and fetuses with and without congenital anomalies. Data were analyzed by
      the generalized estimating equation. RESULTS: Between 2001 and 2014, a total of
      2477 evolutionary pregnancies were notified. Among these pregnancies, 2379 were
      included in the analysis. One hundred thirty-four babies and fetuses had a
      congenital anomaly (4.9%). The major prevalences found among the recorded
      anomalies were congenital heart defects, chromosomal anomalies, and urinary
      defects. However, the risk of congenital anomalies in babies and fetuses
      conceived after FET was not increased compared with babies and fetuses conceived
      after fresh embryo transfer, even when adjusted for confounding factors (p =
      0.40). CONCLUSIONS: There is no increased risk of congenital anomalies in babies
      and fetuses conceived by fresh versus frozen embryo transfer after in vitro
      fertilization with and without micromanipulation. Indeed, distribution of
      congenital anomalies found in our population is consistent with the high
      prevalence of congenital heart defects, chromosomal anomalies, and urinary
      defects that have been found by other authors in children conceived by infertile
      couples when compared to children conceived spontaneously.

PMID- 28444614
TI  - Combined GnRH-agonist and human chorionic gonadotropin trigger improves ICSI
      cycle outcomes in patients with history of poor fertilization.
AB  - PURPOSE: The purpose of this study was to investigate the utility of a combined
      GnRH-agonist (GnRH-a) and human chorionic gonadotropin (hCG) trigger in improving
      ICSI cycle outcomes in patients with poor fertilization history after standard
      hCG trigger in prior ICSI cycles. METHODS: Retrospective cohort study. Patients
      with a fertilization rate of <20% in at least two prior ICSI cycles who
      subsequently underwent another ICSI cycle with hCG trigger were compared to those
      who underwent another ICSI cycle with a combined GnRH-a and hCG trigger. Oocyte
      maturity, fertilization, clinical pregnancy, and live birth rates were compared.
      A multiple linear regression model was used to explore the association between
      combined GnRH-a and hCG trigger (vs hCG trigger alone) and fertilization rate.
      RESULTS: A total of 427 patients with mean age of 37.3 +/- 1.94 years and mean
      baseline fertilization rate of 17.9 +/- 2.03% were included, of which 318 (74.5%)
      and 109 (25.5%) patients underwent a subsequent ICSI cycle with hCG and combined
      GnRH-a and hCG trigger, respectively. The baseline parameters of the male and
      female partner were similar. The mean fertilization rate in the combined trigger
      group was 16.4% (95% CI: 7.58-25.2%) higher than the hCG trigger group, even
      after adjustment for confounders. Patients in the combined trigger group had
      higher oocyte maturity (82.1 vs 69.8%), higher clinical pregnancy (27.5 vs
      5.67%), and higher live birth rates (20.2 vs 3.46%) compared to the hCG trigger
      group. CONCLUSIONS: Combined GnRH-a and hCG trigger in ICSI cycles increase
      oocyte maturity, fertilization, clinical pregnancy, and live birth rates in
      patients with a history of poor fertilization after standard hCG trigger alone.

PMID- 28444616
TI  - Genome-wide identification of grain filling genes regulated by the OsSMF1
      transcription factor in rice.
AB  - BACKGROUND: Spatial- and temporal-specific expression patterns are primarily
      regulated at the transcriptional level by gene promoters. Therefore, it is
      important to identify the binding motifs of transcription factors to better
      understand the networks associated with embryogenesis. RESULTS: Here, we used a
      protein-binding microarray (PBM) to identify the binding motifs of OsSMF1, which
      is a basic leucine zipper transcription factor involved in the regulation of rice
      seed maturation. OsSMF1 (previously called RISBZ1 or OsbZIP58) is known to
      interact with GCN4 motifs (TGA(G/C)TCA) to regulate seed storage protein
      synthesis, and it functions as a key regulator of starch synthesis. Quadruple 9
      mer-based PBM analysis and electrophoretic mobility shift assay revealed that
      OsSMF1 bound to the GCN4 (TGA(G/C)TCA), ACGT (CCACGT(C/G)), and ATGA (GGATGAC)
      motifs with three different affinities. We predicted 44 putative OsSMF1 target
      genes using data obtained from both the PBM and RiceArrayNet. Among these
      putative target genes, 18, 21, and 13 genes contained GCN4, ACGT, and ATGA motifs
      within their 1-kb promoter regions, respectively. Among them, six genes encoding
      major grain filling proteins and transcription factors were chosen to confirm the
      activation of their expression in vivo. OsSMF1 was shown to bind directly to the
      promoters of Os03g0168500 (GCN4 motif), patatin-like gene (GCN4 motif), alpha
      globulin (ACGT motif), rice prolamin box-binding factor (RPBF) (ATGA motif), and
      ONAC024 (GCN4 and ACGT motifs) and to regulate their expression. CONCLUSIONS: The
      results of this study suggest that OsSMF1 is one of the key transcription factors
      that functions in a wide range of seed developmental processes with different
      specific binding affinities for the three DNA-binding motifs.

PMID- 28444615
TI  - Polygenic study of endurance-associated genetic markers ACE I/D, ACTN3
      Arg(R)577Ter(X), CKMM A/G NcoI and eNOS Glu(G)298Asp(T) in male Gorkha soldiers.
AB  - BACKGROUND: Gorkhas, a sub-mountainous population of the Himalayan region, are
      known for strength and bravery. In the present study when "Gorkha" is used
      without brackets, we are mentioning Gorkhas of Tibeto-Burman origin. Physical
      capability, strength and endurance are important components of fitness associated
      with genetic traits. The aim of this study was to examine the endurance potential
      of male Gorkha soldiers, based on endurance-related genetic markers ACE I/D,
      ACTN3 Arg (R)577Ter(X), CKMM A/G NcoI and eNOS Glu(G)298Asp(T). METHODS:
      Genotypic and allelic frequencies were determined in 374 male Gorkha soldiers
      (Tibeto-Burman). These frequencies were compared with frequencies obtained from
      Gorkha (Indo-Aryan), high-altitude natives (Tibeto-Burman) and Indian lowlanders
      (Indo-Aryan). "Total genotype score" (TGS) was calculated from accumulated
      combination of polymorphisms with maximum value "100" for theoretically "optimal"
      polygenic score. Probability of occurrence of "optimal" endurance profile was
      also determined. RESULTS: ACE II genotypic frequency was highest in Tamangs
      followed by Gurungs, Rais, Limbus and Magars. No statistical difference in
      genotypic and allelic frequency of ACTN3 Arg(R)577Ter(X) was noted within the
      groups. Rais showed the highest CKMM A allele frequency (0.908) compared to other
      Gorkha (Tibeto-Burman) groups. Limbus and Tamangs showed the highest eNOS G
      allele frequency (0.938 and 0.915, respectively) compared to that of other
      groups. Probability of male Gorkha soldiers possessing a theoretically optimal
      polygenic endurance profile for four candidate polymorphisms was ~3.35% (1 in
      30). Four percent of the population of male Gorkha soldiers (15 in 374) exhibited
      an optimal TGS 100, and 16% exhibited TGS 87 for endurance compared to male
      Indian soldiers belonging to the lowland (Indo-Aryan) and Gorkha (Indo-Aryan)
      populations suggesting an overall more "favourable" polygenic profile in the male
      Gorkha soldier (Tibeto-Burman) population. CONCLUSIONS: This study presents
      evidence of higher frequency of endurance-associated genes in the Gorkhas
      implying thereby that such genetically endowed individuals from the population
      may be selected and trained for achieving excellence in endurance-related elite
      sports activities.

PMID- 28444617
TI  - Computational Theory Underlying Acute Vestibulo-ocular Reflex Motor Learning with
      Cerebellar Long-Term Depression and Long-Term Potentiation.
AB  - The vestibulo-ocular reflex (VOR) can be viewed as an adaptive control system
      that maintains compensatory eye movements during head motion. As the cerebellar
      flocculus is intimately involved in this adaptive motor control of the VOR, the
      VOR has been a popular model system for investigating cerebellar motor learning.
      Long-term depression (LTD) and long-term potentiation (LTP) at the parallel fiber
      Purkinje cell synapses are considered to play major roles in cerebellar motor
      learning. A recent study using mutant mice demonstrated cerebellar motor learning
      with hampered LTD; the study concluded that the parallel fiber-Purkinje cell LTD
      is not essential. More recently, multiple forms of plasticity have been found in
      the cerebellum, and they are believed to contribute to cerebellar motor learning.
      However, it is still unclear how synaptic plasticity modifies the signal
      processing that underlies motor learning in the flocculus. A computational
      simulation suggested that the plasticity present in mossy fiber-granule cell
      synapses improves VOR-related sensory-motor information transferred into granule
      cells, whereas the plasticity in the molecular layer stores this information as a
      memory under guidance from climbing fiber teaching signals. Thus, motor learning
      and memory are thought to be induced mainly by LTD and LTP at parallel fiber
      Purkinje cell synapses and by rebound potentiation at molecular interneuron
      Purkinje cell synapses among the multiple forms of plasticity in the cerebellum.
      In this study, we focused on the LTD and LTP at parallel fiber-Purkinje cell
      synapses. Based on our simulation, we propose that acute VOR motor learning
      accomplishes by simultaneous enhancement of eye movement signals via LTP and
      suppression of vestibular signals via LTD to increase VOR gain (gain-up
      learning). To decrease VOR gain (gain-down learning), these two signals are
      modified in the opposite directions; namely, LTD suppresses eye movement signals,
      whereas LTP enhances vestibular signals.

PMID- 28444618
TI  - RNA/DNA co-analysis on aged bloodstains from adhesive tapes used for gunshot
      residue collection from hands.
AB  - In cases of firearm related fatalities a systematic investigation at the scene of
      death is indispensable to differentiate between self-inflicted and homicidal
      gunshot injuries. A common method to preserve gunshot residues (GSR) is their
      collection using adhesive tapes. However, the biological material gathered at the
      same time by the tapes would be of special interest if backspatter, ejected from
      the entrance wound against the direction of fire, could be detected. In the
      present study we examined the success rate of co-analysis of RNA and DNA
      recovered from biological traces sampled with adhesive tapes. The material
      originated from eight cases of fatal gunshots, taken from the hands of suspects
      or victims, examined 5 to 19 years ago for GSR. For all types of adhesive tapes
      tested, quantity and quality of the co-extracted nucleic acids was insufficient
      for successful DNA profiling, but was sufficient for the detection of blood
      specific micro RNA (miRNA). In summary, sampling trace evidence from the hands of
      persons involved in fatal gunshots with adhesive tapes has a long-term
      detrimental effect on biological traces.

PMID- 28444619
TI  - The reference cube: A new ballistic model to generate staining in firearm
      barrels.
AB  - After contact shots to the head biological traces can be found inside firearm
      barrels. So far silicone coated, gelatin filled box models were used to generate
      such staining according to the triple contrast method (mixture of acrylic paint,
      barium sulfate and blood sealed in a thin foil bag). This study was conducted to
      develop a transparent ballistic model allowing contact shots. Gelatin filled
      polyethylene bottles with and without a silicone coat were tested in comparison
      to non-covered gelatin blocks. Finally, thin foil bags of 5 cm * 5 cm dimension
      were glued on a synthetic absorbent kitchen wipe on top of which 1 L 10% gelatin
      solution was molded to create blocks of 8.5 cm length. A kitchen wipe with a
      paint pad on its inside formed the front of the cube. Three contact shots each
      with a 9 mm Luger pistol and a .38 special revolver were performed on all model
      variations. The staining was documented by endoscopy and swabs gathered from both
      ends of the barrel were analyzed by quantitative PCR. Reliable staining was
      achieved using the front covered gelatin block with comparable results to the
      silicone coated box model used before. For further research using ballistic
      models to simulate a human head a symmetric form of the gelatin block such as a
      cube is recommended.

PMID- 28444621
TI  - Head of an old goitrous woman.

PMID- 28444620
TI  - Environmental pollution with antimicrobial agents from bulk drug manufacturing
      industries in Hyderabad, South India, is associated with dissemination of
      extended-spectrum beta-lactamase and carbapenemase-producing pathogens.
AB  - PURPOSE: High antibiotic and antifungal concentrations in wastewater from anti
      infective drug production may exert selection pressure for multidrug-resistant
      (MDR) pathogens. We investigated the environmental presence of active
      pharmaceutical ingredients and their association with MDR Gram-negative bacteria
      in Hyderabad, South India, a major production area for the global bulk drug
      market. METHODS: From Nov 19 to 28, 2016, water samples were collected from the
      direct environment of bulk drug manufacturing facilities, the vicinity of two
      sewage treatment plants, the Musi River, and habitats in Hyderabad and nearby
      villages. Samples were analyzed for 25 anti-infective pharmaceuticals with liquid
      chromatography-tandem mass spectrometry and for MDR Gram-negative bacteria using
      chromogenic culture media. In addition, specimens were screened with PCR for bla
      VIM, bla KPC, bla NDM, bla IMP-1, and bla OXA-48 resistance genes. RESULTS: All
      environmental specimens from 28 different sampling sites were contaminated with
      antimicrobials. High concentrations of moxifloxacin, voriconazole, and
      fluconazole (up to 694.1, 2500, and 236,950 ug/L, respectively) as well as
      increased concentrations of eight other antibiotics were found in sewers in the
      Patancheru-Bollaram industrial area. Corresponding microbiological analyses
      revealed an extensive presence of extended-spectrum beta-lactamase and
      carbapenemase-producing Enterobacteriaceae and non-fermenters (carrying mainly
      bla OXA-48, bla NDM, and bla KPC) in more than 95% of the samples. CONCLUSIONS:
      Insufficient wastewater management by bulk drug manufacturing facilities leads to
      unprecedented contamination of water resources with antimicrobial
      pharmaceuticals, which seems to be associated with the selection and
      dissemination of carbapenemase-producing pathogens. The development and global
      spread of antimicrobial resistance present a major challenge for pharmaceutical
      producers and regulatory agencies.

PMID- 28444622
TI  - A brief review of the management of platinum-resistant-platinum-refractory
      ovarian cancer.
AB  - Ovarian cancer, which ranks fifth in cancer deaths among women, is the most
      lethal gynecologic malignancy. Epithelial ovarian cancer (EOC) is the most common
      histologic type, with the 5-year survival for all stages estimated at 45.6%. This
      rate increases to more than 70% in the minority of patients who are diagnosed at
      an early stage, but declines to 35% in the vast majority of patients diagnosed at
      advanced stage. Recurrent EOC is incurable. Platinum sensitivity (or lack
      thereof) is a major determinant of prognosis. The current standard treatment is
      primary surgery followed by platinum-based chemotherapy. In recurrent platinum
      resistant/platinum-refractory EOC, sequential single-agent salvage chemotherapy
      is superior to multiagent chemotherapy. Multiagent regimens increase toxicity
      without clear benefit; however, no preferred sequence of single agents is
      recommended. The impact of targeted therapies and immunotherapies on progression
      free survival and overall survival, which remains dismal, is under active
      investigation. Currently, clinical trials offer the best hope for the development
      of a new treatment paradigm in this recalcitrant disease.

PMID- 28444623
TI  - Treatment adherence in chronic myeloid leukaemia patients receiving tyrosine
      kinase inhibitors.
AB  - Failure to comply with treatment recommendations is very common in patients, but
      still poorly recognised by doctors. The current practice of using oral therapy on
      a large scale has been increasingly adopted for cancer patients. Chronic myeloid
      leukaemia (CML) is just such an example, where the introduction of taking new
      oral medications, the tyrosine kinase BCR-ABL inhibitors (TKI), has now
      revolutionised the treatment. The aim of our study was to assess treatment
      adherence in a group of Polish CML patients (a survey was conducted on 140
      patient aged >=18 years) treated with oral TKI (imatinib, dasatinib and
      nilotinib) taking into account the following variables: gender, age, education,
      place of residence, family circumstances and duration of therapy. In addition, we
      evaluated whether there is a relationship between how patients perceive their
      level of adherence to treatment recommendations with how subjectively the
      required dosage regimen was followed. Half the patients admitted to skipping at
      least one drug dose during the entire course of treatment and 39% did so within
      their last treatment month. Patients were also found to overestimate their own
      adherence assessment; around 60% of those missing at least 1 drug dose within the
      last treatment month believed they 'always' followed recommendations. The study
      demonstrated that adherence deteriorates over time. Furthermore, patients aged
      >65 years and patients suffering at least one comorbid disease had better
      adherence (p < 0.011). There were no differences in adherence among patients
      treated with imatinib, dasatinib and nilotinib (p = 0.249).

PMID- 28444625
TI  - Confused reference in the article entitle: pharmacogenomics of platinum-based
      chemotherapy in non-small cell lung cancer-focusing on DNA repair systems.

PMID- 28444624
TI  - Targeting NTRK fusion in non-small cell lung cancer: rationale and clinical
      evidence.
AB  - In the era of personalized medicine, the identification of targetable genetic
      alterations represented a major step forward in anticancer therapy. NTRK
      rearrangements represent the molecular driver of a subset of solid tumors,
      including 3% of non-small-cell lung cancers (NSCLCs). Preliminary data indicate
      that molecularly selected NSCLC patients harboring NTRK fusions derive an
      unprecedented clinical benefit from Trk-directed targeted therapies. The aim of
      this review is to describe the molecular biology of NTRK signaling pathway and to
      summarize the preclinical data on novel Trk inhibitors, touching upon the
      clinical development of these inhibitors for the treatment of advanced NSCLC,
      which have already shown encouraging anticancer activity and acceptable safety
      profile in early phase I clinical trials.

PMID- 28444626
TI  - Towards new human rights in the age of neuroscience and neurotechnology.
AB  - Rapid advancements in human neuroscience and neurotechnology open unprecedented
      possibilities for accessing, collecting, sharing and manipulating information
      from the human brain. Such applications raise important challenges to human
      rights principles that need to be addressed to prevent unintended consequences.
      This paper assesses the implications of emerging neurotechnology applications in
      the context of the human rights framework and suggests that existing human rights
      may not be sufficient to respond to these emerging issues. After analysing the
      relationship between neuroscience and human rights, we identify four new rights
      that may become of great relevance in the coming decades: the right to cognitive
      liberty, the right to mental privacy, the right to mental integrity, and the
      right to psychological continuity.

PMID- 28444627
TI  - Level of Cigarette Consumption and Duration of Smoking Abstinence During Failed
      Quit Attempts Among Long-Term Daily Smokers: the Role of Race/Ethnicity and
      Cessation Aids.
AB  - The goal of this study was to determine whether race/ethnicity and use of smoking
      cessation aids are associated with the duration of the last serious quit attempt
      and reductions in cigarette consumption among long-term daily smokers who tried,
      and failed, to quit smoking during the preceding year. Data came from the 2010
      2011 Tobacco Use Supplement survey conducted in the USA, and analyses included
      6672 reports of long-term daily smokers (i.e., smokers who smoked daily for 1
      year or longer) who made at least one serious quit attempt in the past 12 months.
      About 39% of these smokers used at least one smoking cessation aid during their
      last quit attempt. Use of aids was significantly lower for non-Hispanic Black
      (NHB, 29%) and Hispanic (HISP, 29%) smokers than for non-Hispanic White (NHW,
      42%) smokers, possibly due to differences in socioeconomic status and access to
      healthcare for smoking cessation. The effect of using any aids on mean cigarette
      reduction and duration of the last long quit attempt (i.e., one that lasted a day
      or more) was similar across race/ethnicity. Using any aids did not substantially
      influence mean cigarette reduction but was positively associated with duration of
      the quit attempt: the duration was 6 days longer (CI = 3:10), on average, when
      aids were used than when smokers attempted to quit unassisted. Race/ethnicity was
      significantly associated with mean cigarette reduction (p = 0.023); non-Hispanic
      American Indian and Alaska Native smokers had the highest mean reduction (of 3
      cigarettes, CI = 1:5) among the racial/ethnic groups considered. Use of aids may
      help increase duration of quit attempts  and thus, may increase likelihood of
      quitting successfully in the near future.

PMID- 28444628
TI  - Moving Beyond Age: An Exploratory Qualitative Study on the Context of Young
      African American Men and Women's Sexual Debut.
AB  - African American youth continue to be disproportionately affected by HIV. Early
      sexual debut has been identified as a major determinant of HIV risk. However,
      emerging research suggests that the overarching context in which first sex occurs
      may have greater implications for sexual health than simply age alone. The
      purpose of this exploratory, qualitative study was to better understand the
      broader context of African Americans' sexual debut. In-depth, semi-structured
      interviews were conducted with 10 African American men and women aged 18-24
      years. Thematic analysis was used to analyze the data. The mean age at sexual
      debut for the sample was 15.4 (SD = 3.3), and youth framed their sexual debut as
      positive (50%), negative (30%), and both positive and negative (20%). The
      majority of youth initiated pre-sex conversations with their partners to gauge
      potential interest in engaging in sexual activity, and all youth utilized at
      least one HIV/sexually transmitted infection and pregnancy prevention method.
      However, most youth failed to talk to their partners prior to sex about their
      past sexual histories and what the experience meant for their relationship. Key
      differences emerged between youth who framed the experience as positive and those
      who framed the experience as negative or both positive and negative in terms of
      their motivations for initiating sex (i.e., readiness to initiate sex, pressure,
      and emotionally safety) and post-sex emotions (i.e., remorse and contentment).
      Findings provide further support for examining the broader sexual context of
      African American's sexual debut. A more comprehensive understanding of sexual
      debut will aid in the development and tailoring of sexual risk reduction programs
      targeting African American youth.

PMID- 28444629
TI  - Stress Measured by Allostatic Load Score Varies by Reason for Immigration: The
      Africans in America Study.
AB  - OBJECTIVE: Reason for immigration as a biological stress has not been studied in
      Africans. Our goal was to determine in African immigrants, if biological stress
      measured by allostatic load score (ALS) varies by reason for immigration.
      METHODS: Using an ALS which had been previously developed with the National
      Health and Nutrition Examination Survey (NHANES) data to assess stress due to
      racism and nativity, ALS was calculated in 85 African immigrants (67% male, age
      42 +/- 10 years). For confirmation, we tested five additional ALS also built from
      NHANES. RESULTS: The two reasons for immigration which consistently had the
      lowest ALS were family reunification and lottery winner for self and immediate
      family. The other reasons for immigration such as study, asylum/refugee, and work
      had higher ALS. As reasons for immigration with the lowest ALS promoted family
      unity, they were combined (group 1) and the Africans who came for other reasons
      were combined (group 2). ALS in group 1 vs. group 2 was 1.96 +/- 1.40 vs. 2.94 +/
      1.87, P = 0.03. CONCLUSIONS: Biological stress varies by reason for immigration
      and appears to be mitigated by maintaining family unity. Overall, reason for
      immigration is an important biographical data likely to influence health.

PMID- 28444630
TI  - New Synthetic Methods for Phosphate Labeling.
AB  - The complexity of phosphorylation pathways and their downstream effects is vast.
      Synthetic chemistry has been working side by side with biology to develop
      phosphate labels for biological processes involving phosphorylated compounds.
      This chapter discusses recently employed methods for the preparation of several
      phosphate labels. Synthesis of biomolecules and their analogs and other useful or
      potentially useful phosphate derivatives is discussed.

PMID- 28444631
TI  - Subacute onset Hirayama disease with extensive myelopathy on MRI in flexed
      posture.

PMID- 28444632
TI  - Post-dengue sacral radiculitis presenting as a cauda equina syndrome: a case
      report.

PMID- 28444634
TI  - Watching diagnoses develop: Eye movements reveal symptom processing during
      diagnostic reasoning.
AB  - Finding a probable explanation for observed symptoms is a highly complex task
      that draws on information retrieval from memory. Recent research suggests that
      observed symptoms are interpreted in a way that maximizes coherence for a single
      likely explanation. This becomes particularly clear if symptom sequences support
      more than one explanation. However, there are no existing process data available
      that allow coherence maximization to be traced in ambiguous diagnostic
      situations, where critical information has to be retrieved from memory. In this
      experiment, we applied memory indexing, an eye-tracking method that affords rich
      time-course information concerning memory-based cognitive processing during
      higher order thinking, to reveal symptom processing and the preferred
      interpretation of symptom sequences. Participants first learned information about
      causes and symptoms presented in spatial frames. Gaze allocation to emptied
      spatial frames during symptom processing and during the diagnostic response
      reflected the subjective status of hypotheses held in memory and the preferred
      interpretation of ambiguous symptoms. Memory indexing traced how the diagnostic
      decision developed and revealed instances of hypothesis change and biases in
      symptom processing. Memory indexing thus provided direct online evidence for
      coherence maximization in processing ambiguous information.

PMID- 28444633
TI  - Distributed representations of action sequences in anterior cingulate cortex: A
      recurrent neural network approach.
AB  - Anterior cingulate cortex (ACC) has been the subject of intense debate over the
      past 2 decades, but its specific computational function remains controversial.
      Here we present a simple computational model of ACC that incorporates distributed
      representations across a network of interconnected processing units. Based on the
      proposal that ACC is concerned with the execution of extended, goal-directed
      action sequences, we trained a recurrent neural network to predict each
      successive step of several sequences associated with multiple tasks. In keeping
      with neurophysiological observations from nonhuman animals, the network yields
      distributed patterns of activity across ACC neurons that track the progression of
      each sequence, and in keeping with human neuroimaging data, the network produces
      discrepancy signals when any step of the sequence deviates from the predicted
      step. These simulations illustrate a novel approach for investigating ACC
      function.

PMID- 28444635
TI  - The Leukocentric Theory of Neurological Disorder: A Manifesto.
AB  - Approximately half of the human brain is composed of white matter (WM), a
      specialized tissue housing the axonal projection of neurons and their necessary
      supporting glial cells. Axons course long distances from their parent soma, have
      a delicate structure, large surface area and in many cases are dependent upon a
      uniquely close morphological arrangement with myelinating oligodendrocyte
      partners; all factors that may predispose them to injury and disease. WM damage
      is central to a range of well-characterized disorders including multiple
      sclerosis and spinal cord injury and is also makes a significant contribution to
      disorders often considered to be largely focused in gray matter; for example, in
      stroke where ~49% of injury by volume is located in WM. In addition, advances in
      brain imaging have revealed early, often prodromal, changes in WM structure in
      most forms of neurodegeneration including Alzheimer's, Huntingdon's and
      Parkinson's diseases as well as during normal cognitive decline and a variety of
      behavioral conditions. The significance of the early WM changes for the etiology
      of these diseases is largely unknown. Subtle, early changes in synaptic function
      may produce the prodromal WM changes evident in imaging, or WM and gray mater
      structures may undergo simultaneous reactions to the underlying disease process.
      However, there are rational mechanisms for the transmission of pathology from WM
      to gray matter and this article suggests an alternative hypothesis: that WM
      pathology precedes and to some extent is causal of synaptic dysfunction in many
      common neurological disorders. Neurological disorders that have their origin or
      their principle lesion in WM are here defined as "leukopathologies".

PMID- 28444636
TI  - Modulatory Effects of Perineuronal Oligodendrocytes on Neuronal Activity in the
      Rat Hippocampus.
AB  - Action potentials are fundamental to relaying information from region to region
      in the nervous system. Changes in action potential firing patterns in neural
      circuits influence how the brain processes information. In our previous study, we
      focused on interneuron/perineuronal astrocyte pairs in the hippocampal CA1 region
      and reported that direct depolarization of perineuronal astrocytes modulated the
      firing pattern of interneurons. In the current study, we investigated the
      morphological and electrophysiological properties of perineuronal
      oligodendrocytes, and examined their modulatory effects on interneuronal firing
      in the CA1 region. Perineuronal oligodendrocytes only had a few processes, which
      were crooked, intricately twisted, and twined around the soma and proximal region
      of the main processes of adjacent interneurons. Whole-cell current patterns of
      perineuronal oligodendrocytes were homogenous and the current-voltage
      relationship showed remarkable outward rectification. Although the K+ channel
      blockers, tetraethylammonium and 4-aminopyridine, clearly blocked outward
      currents, Ba2+ did not significantly alter whole-cell currents. Unlike
      perineuronal astrocytes, the depolarization of perineuronal oligodendrocytes had
      no effect on interneuronal firing; however, when the interneurons were firing at
      a higher frequency, the hyperpolarization of perineuronal oligodendrocytes
      suppressed their action potentials. The suppressive effects of perineuronal
      oligodendrocytes were inhibited in the presence of a low concentration of
      tetraethylammonium, which selectively blocked deep and fast
      afterhyperpolarization. These results suggest that perineuronal oligodendrocytes
      suppress interneuronal firing through their influence on K+ channels, which are
      responsible for deep and fast afterhyperpolarization.

PMID- 28444638
TI  - Nuclear Cardiology: Are We Using the Right Protocols and Tracers the Right Way?
AB  - The field of nuclear cardiology has changed considerably over recent years, with
      greater attention paid to safety and radiation protection issues. The wider usage
      of technetium-99m (Tc-99m)-labeled radiopharmaceuticals for single-photon
      emission computed tomography (SPECT) imaging using gamma cameras has contributed
      to better quality studies and lower radiation exposure to patients. Increased
      availability of tracers and scanners for positron emission tomography (PET) will
      help further improve the quality of studies and quantify myocardial blood flow
      and myocardial flow reserve, thus enhancing the contribution of non-invasive
      imaging to the management of coronary artery disease. The introduction of new
      instrumentation such as solid state cameras and new software will help reduce
      further radiation exposure to patients undergoing nuclear cardiology studies.
      Results from recent studies, focused on assessing the relationship between best
      practices and radiation risk, provide useful insights on simple measures to
      improve the safety of nuclear cardiology studies without compromising the quality
      of results.

PMID- 28444637
TI  - Phase-Dependent Astroglial Alterations in Li-Pilocarpine-Induced Status
      Epilepticus in Young Rats.
AB  - Epilepsy prevalence is high in infancy and in the elderly population. Lithium
      pilocarpine is widely used to induce experimental animal models of epilepsy,
      leading to similar neurochemical and morphological alterations to those observed
      in temporal lobe epilepsy. As astrocytes have been implicated in epileptic
      disorders, we hypothesized that specific astroglial changes accompany and
      contribute to epileptogenesis. Herein, we evaluated time-dependent astroglial
      alterations in the hippocampus of young (27-day-old) rats at 1, 14 and 56 days
      after Li-pilocarpine-induced status epilepticus (SE), corresponding to different
      phases in this model of epilepsy. We determined specific markers of astroglial
      activation: GFAP, S100B, glutamine synthetase (GS), glutathione (GSH) content,
      aquaporin-4 (AQP-4) and potassium channel Kir 4.1; as well as epileptic
      behavioral, inflammatory and neurodegenerative changes. Phase-dependent signs of
      hippocampal astrogliosis were observed, as demonstrated by increments in GFAP,
      S100B and GS. Astrocyte dysfunction in the hippocampus was characterized, based
      on the decrease in GSH content, AQP-4 and Kir 4.1 channels. Degenerating neurons
      were identified by Fluoro-Jade C staining. We found a clear, early (at SE1) and
      persistent (at SE56) increase in cerebrospinal fluid (CSF) S100B levels.
      Additionally, serum S100B was found to decrease soon after SE induction,
      implicating a rapid-onset increase in the CSF/serum S100B ratio. However, serum
      S100B increased at SE14, possibly reflecting astroglial activation and/or long
      term increase in cerebrovascular permeability. Moreover, we suggest that
      peripheral S100B levels may represent a useful marker for SE in young rats and
      for follow up during the chronic phases of this model of epilepsy. Together,
      results reinforce and extend the idea of astroglial involvement in epileptic
      disorders.

PMID- 28444639
TI  - Metformin and Prostate Cancer: a New Role for an Old Drug.
AB  - PURPOSE OF REVIEW: Since epidemiological studies first demonstrated a potential
      positive effect of metformin in reducing cancer incidence and mortality, there
      has been an increased interest in not only better understanding metformin's
      mechanisms of action but also in exploring its potential anti-cancer effects. In
      this review, we aim to summarise the current evidence exploring a role for
      metformin in prostate cancer therapy. RECENT FINDINGS: Preclinical studies have
      demonstrated a number of antineoplastic biological effects via a range of
      molecular mechanisms. Data from retrospective epidemiological studies in prostate
      cancer has been mixed; however, there are several clinical trials currently
      underway evaluating metformin's role as an anti-cancer agent. Early studies have
      shown benefits of metformin to inhibit cancer cell proliferation and improve
      metabolic syndrome in prostate cancer patients receiving androgen deprivation
      therapy (ADT). While the body of evidence to support a role for metformin in
      prostate cancer therapy is rapidly growing, there is still insufficient data from
      randomised trials, which are currently still ongoing. However, evidence so far
      suggests metformin could be a useful adjuvant agent, particularly in patients on
      ADT.

PMID- 28444640
TI  - Diagnostic value of the dual-luciferase report assay for predicting response to
      glucocorticoid in children with acute lymphoblastic leukemia.
AB  - OBJECTIVE: Resistance to glucocorticoid (GC) is a significant clinical problem in
      some cases of acute lymphoblastic leukemia (ALL). Current methods of assessing GC
      resistance are time consuming and have limited reproducibility; in this study, we
      sought to define a new method of evaluating GC sensitivity and resistance in
      vitro. METHODS: Based on the mechanisms of GC resistance, we hypothesized that
      the dual-luciferase report (DLR) assay could reflect the transcription effects of
      GC downstream of the GC-glucocorticoid receptor signaling pathway, thereby
      allowing the evaluation of reactions to GC. Sixty-two patients with differential
      GC response were included in this study. The prednisone induction test was used
      to divide the children with ALL into two groups: GC sensitive (GCS) and GC
      resistant (GCR). DLR assay was later conducted on those patients to evaluate its
      value for diagnosis of the GC reactivity. Receiver operating characteristic
      curves were used to identify the optimal assay cutoff for identifying response to
      GC. RESULTS: Using the DLR assay analysis, we found that GCR subjects showed
      significantly lower reporter/control ratios for luciferase, as compared with GCS
      subjects. The optimal cutoff value for GC response was 0.67, with sensitivity of
      77.1% and specificity of 93.3%. The DLR assay results were consistent with
      prednisone induction test results. Further, the DLR assay was simpler, more
      sensitive, and less time-consuming than the prednisone induction test.
      CONCLUSIONS: Our study showed that the DLR assay is relatively fast, simple, and
      sensitive. Accordingly, it could be useful for detecting GC response in children
      with ALL.

PMID- 28444641
TI  - Correlation of preoperative ROMA scores with clinical stage in epithelial ovarian
      cancer patients.
AB  - PURPOSE: The significance of the Risk of Ovarian Malignancy Algorithm (ROMA) in
      differentiating benign and malignant ovarian lesions has been evidenced. In our
      clinical work, we found that advanced ovarian cancer were accompanied commonly
      with high ROMA scores. Thus, this study aimed to clarify the performance of ROMA
      in different disease stage of epithelial ovarian cancer (EOC) prior to surgery.
      METHODS: Carbohydrate antigen (CA125) and human epididymis protein 4 (HE4) levels
      and ROMA scores in 221 patients with FIGO stage I, II or III/IV stage EOC were
      analyzed. The positive rates of CA125, HE4 and ROMA at each disease stage were
      calculated. Their cutoff values, sensitivity, specificity, accuracy, positive
      predictive value (PPV), and negative predictive value (NPV) for distinguishing
      patients with FIGO stage I/II from those with FIGO stage III/IV were estimated
      via ROC curves. RESULTS: Serum CA125 and HE4 levels and ROMA scores rose
      significantly with advancing stage. ROMA and CA125 were significantly elevated
      more frequently in comparing with HE4 in EOC patients at with the same stage.
      Based on ROC curves, the cutoff values for FIGO stage III/IV EOC were 110 IU/mL,
      126 pmol/L, 78 and 68% for CA125, HE4, premenopausal and postmenopausal ROMA,
      respectively. ROMA was the strongest predictor of FIGO stage, with the highest
      specificity, accuracy, and PPV, which were 84.4, 82.5, and 87.0% for
      postmenopausal patients, 89.3, 85.6, and 74.3% for premenopausal patients.
      CONCLUSIONS: Our data suggest high ROMA scores correlated with advanced ovarian
      cancer prior to surgery. These observations suggest potential utility of ROMA in
      the comprehensively preoperative evaluation of EOC patients.

PMID- 28444642
TI  - Breast self-exam and patient interval associate with advanced breast cancer and
      treatment delay in Mexican women.
AB  - PURPOSE: The objective of this study was to compare treatment intervals in breast
      cancer patients according to the detection method (breast self-exam vs
      screening). PATIENTS AND METHODS: We conducted a retrospective analysis including
      291 breast cancer patients at a Mexican tertiary referral hospital. RESULTS:
      Breast cancer detection method was mostly breast self-exam (60%). The median
      patient interval was 60.5 days, and was associated with marital status and
      socioeconomic level. Differences between the two groups were statistically
      significant for global interval, p = 0.002; however, health system interval was
      not statistically different. CONCLUSION: In our country, breast cancer screening
      is opportunistic, with several weaknesses within its management and quality
      systems. Our study showed that even in specialized health care centers, breast
      cancer is detected by self-exam in up to 2/3 of patients, which can explain the
      advanced stages at diagnosis in our country. In developing countries, the
      immediate health care access for breast cancer patients should be prioritized as
      an initial step to reduce the global treatment initiation interval in order to
      reduce mortality.

PMID- 28444643
TI  - Fostering incidental experiences of nature through green infrastructure planning.
AB  - Concern for a diminished human experience of nature and subsequent decreased
      human well-being is addressed via a consideration of green infrastructure's
      potential to facilitate unplanned or incidental nature experience. Incidental
      nature experience is conceptualized and illustrated in order to consider this
      seldom addressed aspect of human interaction with nature in green infrastructure
      planning. Special attention has been paid to the ability of incidental nature
      experience to redirect attention from a primary activity toward an unplanned
      focus (in this case, nature phenomena). The value of such experience for human
      well-being is considered. The role of green infrastructure to provide the
      opportunity for incidental nature experience may serve as a nudge or guide toward
      meaningful interaction. These ideas are explored using examples of green
      infrastructure design in two Nordic municipalities: Kristianstad, Sweden, and
      Copenhagen, Denmark. The outcome of the case study analysis coupled with the
      review of literature is a set of sample recommendations for how green
      infrastructure can be designed to support a range of incidental nature
      experiences with the potential to support human well-being.

PMID- 28444644
TI  - Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a
      phase 1/2 study.
AB  - In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and
      assessed its recommended dose in Japanese patients with chronic myeloid leukemia
      (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia
      chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant/intolerant to
      >=1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the
      recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in
      chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6
      months in patients with advanced phase disease (Phase 2). MCyR was
      achieved/maintained by 12 months in 65% of CP-CML patients; MaHR was achieved by
      6 months in 61% of patients with advanced phase disease. The most common
      nonhematologic grade 3/4 treatment-emergent adverse event (AE) was hypertension
      (37%); common hematologic grade 3/4 AEs were thrombocytopenia (57%), neutropenia
      (34%), and leukopenia (26%). Overall, five (14%) patients experienced arterial
      occlusive events (AOEs); no grade 5 AOEs were reported. The steady-state
      accumulation ratio of ponatinib (based on area under the curve) ranged from 2.6
      (15 mg/day) to 1.3 (45 mg/day). In summary, ponatinib demonstrated efficacy in
      Japanese patients with CML and Ph+ALL resistant/intolerant to prior TKI
      treatment; safety data support a recommended starting dose of 45 mg/day in these
      patients.

PMID- 28444646
TI  - Comment on: "Determining Strength: A Case for Multiple Methods of Measurement".

PMID- 28444647
TI  - [Partial Fasciectomy and Options of Reconstruction Using Local Flaps in Cases of
      Dupuytren's Disease].
AB  - Aim: Partial fasciectomy in cases of grade III-IV Dupuytren's contracture and
      coverage of the defect with local flaps. Indication: Dupuytren's contracture is a
      progressive disease of the hand associated with the formation of fascial cords,
      which may result in flexion and adduction contractures of the fingers leading up
      to complete dysfunction of the hands. Method: If several fingers are affected,
      partial fasciectomy is the gold standard in the treatment of Dupuytren's
      contracture. Ideally, the fingers reach the neutral position after the fibres
      causing the contracture are resected and arthrolysis is performed as needed. The
      skin deficits resulting from restored extension have to be covered by the use of
      Z-plasties, local or pedicled flaps of the hand. Conclusion: The resection of
      contracting cords in advanced cases of Dupuytren's contracture leads to large
      soft tissue defects. The microsurgical preparation of nerve and vascular
      structures is often difficult because of the fascial cords surrounding them.
      Exact preoperative planning of the extent of resection, as well as reconstruction
      options are essential and determine how incisions are made. To prevent a relapse,
      it is essential to reverse skin fibre direction using flaps and to insert intact
      skin with preserved subdermal adipose tissue.

PMID- 28444645
TI  - Outdoor Ambient Air Pollution and Neurodegenerative Diseases: the
      Neuroinflammation Hypothesis.
AB  - PURPOSE OF REVIEW: Accumulating research indicates that ambient outdoor air
      pollution impacts the brain and may affect neurodegenerative diseases, yet the
      potential underlying mechanisms are poorly understood. RECENT FINDINGS: The
      neuroinflammation hypothesis holds that elevation of cytokines and reactive
      oxygen species in the brain mediates the deleterious effects of urban air
      pollution on the central nervous system (CNS). Studies in human and animal
      research document that neuroinflammation occurs in response to several inhaled
      pollutants. Microglia are a prominent source of cytokines and reactive oxygen
      species in the brain, implicated in the progressive neuron damage in diverse
      neurodegenerative diseases, and activated by inhaled components of urban air
      pollution through both direct and indirect pathways. The MAC1-NOX2 pathway has
      been identified as a mechanism through which microglia respond to different forms
      of air pollution, suggesting a potential common deleterious pathway. Multiple
      direct and indirect pathways in response to air pollution exposure likely
      interact in concert to exert CNS effects.

PMID- 28444649
TI  - [Cystic Fibrosis Screening in Germany].

PMID- 28444648
TI  - [In process].

PMID- 28444650
TI  - [Newborn Screening on Cystic Fibrosis in Germany: Comparison of the new Screening
      Protocol with an Alternative Protocol].
AB  - Background For the new cystic fibrosis (CF) newborn screening program in Germany
      the Federal Joint Committee (G-BA) implemented a new screening protocol using
      immunoreactive trypsinogen (IRT) as first and pancreatitis associated protein
      (PAP) as second tier. Gene analysis with a panel of 31 CFTR-mutations is used as
      third tier to increase the positive predictive value (PPV) which is known to be
      low in pure biochemical IRT/PAP protocols. Methods For post hoc analysis the data
      pool (n=372 906) of a study evaluating a pure biochemical IRT/PAP protocol was
      used for assessment of the 3-step G-BA protocol in comparison with an alternative
      screening protocol recommended by the authors. The difference between the 2
      protocols is the procedure when IRT>99.9th percentile. In the G BA protocol PAP
      and DNA analysis will be by-passed while in the alternative protocol only the PAP
      step will be circumvented. Results Both 3-tier IRT/PAP+SN/DNA protocols did not
      lose sensitivity due to addition of genetic analysis when the results were
      compared to those of the 2-tier biochemical IRT/PAP protocol. However, the
      protocols provide different results regarding PPV. The G-BA protocol showed with
      351 a much higher number of false-positively detected newborns (PPV 20.2%) when
      compared to 31 false-positively detected newborns in the alternative protocol
      (PPV 69.6%). Conclusions The G-BA protocol had a worse performance when compared
      with the alternative protocol recommended by the authors. The higher number of
      false-positively detected newborns using the G-BA protocol will lead to more
      consultations including sweat tests, will create more anxiety in parents, and
      will result in higher costs after screening.

PMID- 28444651
TI  - [MRI-Based Ratio of Fetal Lung to Body Volume as New Prognostic Marker for
      Chronic Lung Disease in Patients with Congenital Diaphragmatic Hernia].
AB  - Background Our aim was to evaluate the prognostic value of magnetic resonance
      imaging (MRI)-based ratio of fetal lung volume (FLV) to fetal body volume (FBV)
      as a marker for development of chronic lung disease (CLD) in fetuses with
      congenital diaphragmatic hernia (CDH). Patients and Methods FLV and FBV were
      measured and the individual FLV/FBV ratio was calculated in 132 fetuses.
      Diagnosis of CLD was established following prespecified criteria and graded into
      mild/moderate/severe if present. Logistic regression analysis was used to
      calculate the probability of postnatal development of CLD in dependence of the
      FLV/FBV ratio. Receiver operating characteristic curves were analysed by
      calculating the area under the curve to evaluate the prognostic accuracy of this
      marker. Results 61 of 132 fetuses developed CLD (46.21%). The FLV/FBV ratio was
      significantly lower in fetuses with CLD (p=0.0008; AUC 0.743). Development of CLD
      was significantly associated with thoracic herniation of liver parenchyma
      (p<0.0001), requirement of extracorporal membrane oxygenation (ECMO) (p<0.0001)
      and gestational age at delivery (p=0.0052). Conclusion The MRI-based ratio of FLV
      to FBV is a highly valuable prenatal parameter for development of CLD. The ratio
      is helpful for early therapeutic decisions by estimating the probability to
      develop CLD. Perinatally, gestational age at delivery and ECMO requirement are
      useful additional parameters to further improve prediction of CLD.

PMID- 28444652
TI  - [Establishment of Specialized Pediatric Palliative Home Care in the Medical
      Valley of the European Metropolitan Area Nuremberg].
AB  - Background As part of the 2007 health reform in Germany the structure of
      outpatient palliative care for children and adolescents was adopted for the first
      time and then implemented in Erlangen-Nuremberg in 2009. Methods The introduction
      of Pediatric Palliative Home Care (PPHC) at the Hospital for Children and
      Adolescents at the University of Erlangen-Nuremberg was retrospectively analyzed
      between the years 2009 to 2014. Referring medical records (paper-based and
      electronic) were evaluated systematically. Results Considering 69 patients within
      this study, 44 (63.8%) died during the investigated period and 61% of these
      Patients deceased at home. 60 patients (87%) had a written emergency plan, which
      was jointly developed with patients and particularly their parents and relatives
      in cooperation with the PPHC team. Over the years and with increasing experience,
      the number and duration of emergency hospitalization decreased. Even complex
      therapies, such as patient-controlled analgesia with PCA pump could be
      implemented on an outpatient basis. Conclusion The descriptive cohort study
      demonstrates that palliative care for children, despite the medical and
      structural complexity is possible in an ambulatory setting. It allows a similar,
      if not better care, compared to inpatient palliative care for children and
      adolescents, not only for the affected patients, but also for their families.

PMID- 28444653
TI  - Trichobezoar (Rapunzel Syndrome) Causing Severe Anaemia and Cardiac Failure.

PMID- 28444654
TI  - Digoxin Toxicity in a Neonate Caused by the Interaction with Carvedilol.

PMID- 28444655
TI  - Bilateral Infiltrative Dacryoadenitis and Granulomatous Pneumonia in an 11-Year
      Old Boy: A Case Report.

PMID- 28444656
TI  - Subacute Myocarditis Associated with Bocavirus Infection in an 8-Week-Old Infant.

PMID- 28444657
TI  - [Diabetes Insipidus Centralis as First Symptom of an Infundibulohypophysitis].

PMID- 28444659
TI  - New Psychoactive Substances (NPS) - a Challenge for the Addiction Treatment
      Services.
AB  - Over the last few years, hundreds of new psychoactive substances (NPS) have been
      identified in Europe. Apart from some herbal compounds, NPS mainly include
      synthetic cannabinoids and a range of new synthetic stimulants (e. g.,
      cathinones). Synthetic NPS are often developed whilst modifying the basic
      chemical (e. g., phenethylamine or tryptamine) structure. Although the
      pharmacology and toxicology of most NPS are hardly known, they are being offered,
      especially online, as "bath salts," as "incense mixtures," or under other
      misleading labels. In addition, NPS are advertised as "legal highs," suggesting
      that, in contrast to substances regulated by the national laws, trading with NPS
      is legal. Although only little is known about the prevalence of NPS use, some of
      these molecules may be associated with a range of severe adverse reactions.
      Indeed, different from cannabis, synthetic cannabinoid users may present with
      epileptic seizures, loss of consciousness, and a range of persisting
      psychopathological disorders. Future studies should inform better-tailored
      management strategies.

PMID- 28444658
TI  - Comparing the Immune-Genomic Effects of Vilazodone and Paroxetine in Late-Life
      Depression: A Pilot Study.
AB  - Vilazodone is a novel antidepressant agent that combines selective serotonin (5
      HT) reuptake inhibitor (SSRI) activity and 5-HT(1A) receptor partial agonist
      activity. A pilot study was conducted to compare vilazodone (novel compound) and
      paroxetine (gold standard) on antidepressant effects, tolerability, and
      inflammation and immune modulation. A 12-week, double-blind, randomized clinical
      trial was conducted with 56 nondemented older adults diagnosed with major
      depressive disorder (MDD). Between-group differences in mood, tolerability, and
      safety, as well as genomic markers of inflammation and immune modulation, were
      examined. Both treatment groups demonstrated similar improvement in depressed
      mood. Leukocyte gene expression profiles demonstrated reduction of specific
      proinflammatory gene transcripts and bioinformatic indications of reduced nuclear
      factor kappa B (NF-kappaB), activator protein (AP)-1, and cAMP response element
      binding (CREB) activity in the vilazodone group compared to the paroxetine group.
      Transcript origin analyses implicated monocytes and dendritic cells as the
      primary cellular origins of transcript reductions in the vilazodone-treated
      group. Vilazodone's antidepressant effects may be associated with reduction of
      proinflammatory gene expression and immune modulation. Further research is
      required.

PMID- 28444660
TI  - Effects of Cycling and Exergaming on Neurotrophic Factors in Elderly Type 2
      Diabetic Men - A Preliminary Investigation.
AB  - Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing
      neurodegenerative diseases. There is growing evidence that repeated exercise
      induced transient increases in neurotrophic factors can augment neurogenesis and
      neuroplasticity. This pilot study compares the effects of 30-min submaximal
      cycling with those of exergaming (combining exercise and video gaming) at the
      same duration and same rating of perceived exertion (BORG RPE: 14-15) on serum
      neurotrophic factors in 8 elderly non-insulin-dependent T2DM patients (71+/-4
      years) (2*2 crossover design). Brain-derived neurotrophic factor (BDNF), vascular
      endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-1 levels
      were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Heart rates
      were almost equal during cycling and exergaming, while lactate values were
      significantly higher during cycling (cycling versus exergaming: 3.7+/-1.1 versus
      2.5+/-1.2 mmol/l, p<0.05). BDNF and VEGF levels were increased significantly post
      cycling (+20%,+14%, p<0.05). No other significant pre-post changes were evident.
      This study demonstrates that acute exercise can increase neurotrophic factors
      (BDNF, VEGF) in elderly T2DM patients, depending on exercise mode.

PMID- 28444661
TI  - Influence of the SLCO1B3 Gene on Sulfonylurea Failure in Patients with Type 2
      Diabetes in China.
AB  - Sulfonylureas are widely used class of drugs for the treatment of type 2 diabetes
      (T2DM). Recent research has demonstrated that SLCO1B3 functions as a determinant
      of the insulinotropic effect of glibenclamide at the tissue level. However,
      whether this gene can influence the efficacy of glibenclamide in type 2 diabetic
      patients is not currently well-understood. All of our study subjects were
      enrolled from the Xiaoke Pills Clinical Trial. The subjects were treated with
      glibenclamide, and followed for 48 weeks. The rs4149117 genotype (T334G) in the
      SLCO1B3 gene was identified by direct sequencing. Relationships between genotype
      and efficacy and safety outcomes were evaluated by logistic or linear regression
      models as appropriate. A total of 374 subjects were enrolled in this study. The
      average age was 54.4+/-8.9 years, the percentage of males was 52.9%, and 91% of
      participants finished the genotype analysis successfully. Logistic regression
      analysis demonstrated that there was no significant difference between genotype
      and treatment failure of glibenclamide under an additive genetic model after
      adjusting for age, sex, renal function and diabetes duration (OR=1.009, 95% CI
      0.692-1.473, P=0.961). The linear regression model demonstrated that the
      rs4149117 mutation in SLCO1B3 was significantly associated with a reduction in
      FPG after 48 weeks of treatment, independent of age, sex, renal function and
      diabetes duration (P=0.017, beta=0.130). In safety outcome analysis, we observed
      that rs4149117 had no association with hypoglycaemia. The rs4149117 mutation in
      the SLCO1B3 gene is not associated with sulfonylurea efficacy.

PMID- 28444662
TI  - Early Mitochondrial Adaptations in Skeletal Muscle to Obesity and Obesity
      Resistance Differentially Regulated by High-Fat Diet.
AB  - The mechanism for different susceptibilities to obesity after short-term high-fat
      diet (HFD) feeding is largely unknown. Given the close association between
      obesity occurrence and mitochondrial dysfunction, the early events in skeletal
      muscle mitochondrial adaptations between HFD-induced obesity (DIO) and HFD
      induced obesity resistant (DIO-R) lean phenotype under excess nutritional
      environment were explored.ICR/JCL male mice were randomly divided into 2 groups,
      as follows: low-fat diet (LFD) and HFD groups. After 6 weeks on HFD, HFD-fed mice
      were classified as DIO or DIO-R according to their body weight gain. Serum
      parameters, oxidative stress biomarkers, the activation of AMPK/ACC axis, and the
      expression profiles of mitochondrial biogenesis were measured by using
      corresponding methods among the LFD control, DIO, and DIO-R groups. Serum
      glucose, total cholesterol, low-density lipoprotein, and high-density lipoprotein
      levels were significantly increased in DIO and DIO-R mice compared with LFD
      controls. However, DIO-R mice had significantly higher MDA levels and exhibited a
      significantly higher level of AMP-activated protein kinase (AMPK) activation and
      acetyl-CoA carboxylase (ACC) inactivation than DIO mice. Furthermore, the
      transcript and protein levels of transcriptional coactivator peroxisome
      proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha)
      and estrogen-related receptor-alpha (ERRalpha) in DIO-R mice were significantly
      up-regulated compared with the DIO mice. Although the body weight gain differed,
      the DIO and DIO-R mice had similar metabolic disturbance of glucose and lipids
      after short-term HFD consumption. The diverse alterations on fatty acid oxidation
      and mitochondrial biogenesis pathway induced by AMPK activation might be involved
      in different susceptibilities to obesity when consuming HFD.

PMID- 28444663
TI  - Transcriptional Coactivator p300 and Silent Information Regulator 1 (SIRT1) Gene
      Polymorphism Associated with Diabetic Kidney Disease in a Chinese Cohort.
AB  - One of the most serious complications of diabetes mellitus, which could lead to
      end-stage renal disease across all demographics, is 'diabetic kidney disease'.
      However, how diabetic kidney disease develops remains unclear. Studies conducted
      thus far suggest that a major factor in the origination and development of the
      disease occurs through histone acetylation modifications. This study aims to
      examine the probable relationship in Chinese patients suffering from type 2
      diabetes. A case-control study was conducted in the Chongqing region of China on
      the Chinese Han population. Patients suffering from type 2 diabetes mellitus were
      selected between March 2014 and Dec 2014 from the Department of Endocrinology,
      which is the First Affiliated Hospital of Chongqing Medical University. TaqMan
      probes were employed to perform an allelic discrimination assay for genotyping
      p300 and the SIRT1 (Silent Information Regulator 1) polymorphism. The risk
      factors diabetic kidney disease were determined by statistical analysis. The
      dispersion of the p300 genotype frequencies and SIRT1 gene polymorphism adheres
      to the Hardy-Weinberg equilibrium. The DKD group had a greater allele G frequency
      distribution, and allele G patients have a higher probability of diabetic kidney
      disease. Female patients, patients younger than 65 years of age, and those with
      the AG or GG genotype are more likely to develop diabetic kidney disease than
      patients with the AA phenotype. Patients with the AG or GG genotype are more
      likely to suffer from a severe diabetic kidney disease than patients with the AA
      genotype, particularly if the patients are older than 65 years of age. The SIRT1
      rs4746720 allele C is a risk factor for urinary Alb/Cr. Allele G and the TC
      genotype patients are more likely to develop diabetic kidney disease, while
      allele G and TT genotype patients are more likely develop a severe diabetic
      kidney disease. Transcriptional coactivator p300 gene polymorphism correlates
      with the development and advancement of diabetic kidney disease. Additionally,
      the SIRT1 gene collaborates with the p300 gene and participates in promoting
      albuminuria in type 2 diabetes mellitus patients.

PMID- 28444665
TI  - Genetic Polymorphisms of Antioxidant and Antiglycation Enzymes and Diabetic
      Complications. How Much Can we Learn from the Genes?
AB  - There is growing evidence that reactive metabolites, such as reactive oxygen
      species and dicarbonyls contribute to diabetic complications. Formation,
      accumulation, and detoxification of these metabolites are controlled by several
      enzymes, some of which have genetically determined levels of expression or
      function. This review not only gives an overview of the different SNPs studied in
      patients with diabetes mellitus type 1 and type 2, but in addition attempts to
      bridge the gap between a genetic study and clinical use. Therefore, not only the
      results of the studies are reviewed, but also their use in identification of
      subgroups where an increased or decreased risk for a diabetic complication is
      described, as well as their use in developing novel therapeutic options based on
      understanding the contribution of an enzyme to a given complication.

PMID- 28444664
TI  - Endocrine Complications of Surgical Treatment of Thyroid Cancer: An Update.
AB  - Postoperative hypoparathyroidism (HypoPT) and hypothyroidism (HypoT) are the main
      endocrine complications after the surgical treatment for thyroid cancer.
      Postsurgical HypoPT can be transient, protracted or permanent. Its frequency
      varies according to the underlying cervical pathology, surgical technique, and
      mainly the experience of the surgeon. Risk factors for HypoPT include
      aggressiveness of the tumor, extent of surgery, the presence of parathyroid gland
      in the pathologic specimen, and surgeon experience. Clinical manifestations of
      postsurgical HypoPT can be acute or chronic. An adequate surgical technique that
      minimizes trauma and preserve the vascularization of the parathyroid glands is
      the better procedure to reduce the risk of postoperative HypoPT. Acute
      hypocalcemia may be managed with intravenous or oral calcium supplements,
      according to the level of serum calcium and the presence of signs and symptoms.
      Patients with permanent HypoPT require lifelong calcium and vitamin D
      supplementation. Calcitriol is the vitamin D metabolite of preference because of
      its high activity and short half-life. Both PTH (1-34) and intact PTH (1-84) have
      demonstrated to be attractive options in hypoparathyroid patients who cannot
      maintain stable serum and urinary calcium levels with calcium and vitamin D
      supplementation. However, the long-term safety of these preparations has not been
      established. Postsurgical HypoT is an unavoidable consequence of total or near
      total thyroidectomy for thyroid cancer. Replacement and suppressive therapy are
      necessary in these patients. Thyroid hormone suppression therapy has shown to be
      accompanied by a decreased risk of disease progression and recurrence; however,
      it may also be associated with increased risk of dysrhythmia and loss of bone
      mass. Therefore, the intensity of TSH suppression must be established in a
      personalized way after balancing risk and benefits, according to the severity of
      the thyroid cancer, the response to therapy, and the individual risk factors for
      adverse events.

PMID- 28444666
TI  - Markers of Bone and Cartilage Turnover.
AB  - Over the past few decades, scientists have been trying to identify tissue
      specific markers that would help to better understand the pathogenesis of bone
      and cartilage diseases and could be used clinically for the screening, diagnosis
      and follow-up of bone or joint diseases. Historically, only a few components
      known to be involved in bone, mineral or cartilage turnover were available for
      this purpose (e. g., urine hydroxyproline, serum and urine calcium and phosphate
      levels). However, since most if not all of these substances have wider biological
      functions beyond bone, mineral and cartilage metabolism, their clinical value as
      tissue-specific markers was limited. Hence, there was a need to identify more
      specific indices of bone and cartilage metabolism. Since the 1980s, a number of
      collagenous and non-collagenous breakdown products as well as cell-specific
      enzymes have been discovered and developed into markers of musculoskeletal tissue
      metabolism. This review describes their chemical and biological function,
      available analytical methods and possible clinical applications.

PMID- 28444667
TI  - Clinical Significance of Antinuclear and Antiextractable Nuclear Antigen Antibody
      in Childhood Immune Thrombocytopenia.
AB  - This study aims to determine the clinical significance of positive
      antinuclear/antiextractable nuclear antigen (ANA/A-ENA) antibody on manifestation
      and therapeutic response of childhood immune thrombocytopenia (ITP). Overall,
      1,330 patients aged between 1 and 15.6 years diagnosed with primary ITP were
      retrospectively analyzed, excluding those with secondary ITP. Bleeding
      manifestations were recorded. All patients underwent autoantibody testing and
      follow-up for 32 months on average (range: 23-54 months). Steroid response was
      also assessed. Response rates were compared between ANA/A-ENA-positive and ANA/A
      ENA-negative patients. Of all the patients enrolled, 84 tested positive only for
      ANA, 102 tested positive for A-ENA, 54 tested positive for both ANA and A-ENA,
      and 1,090 tested negative for both. Patients who were ANA/A-ENA positive were
      more likely to be female and older than 10 years. Patients who were A-ENA
      positive were more likely to have either persistent or chronic disease and suffer
      from life-threatening bleeding as well as poor short-term therapeutic response.
      We conclude that autoantibody testing is important to determine the short-term
      prognosis of ITP patients. Females, patients older than 10 years of age, and
      patients with either mixed positivity or A-ENA positivity should be more closely
      monitored.

PMID- 28444668
TI  - ?

PMID- 28444669
TI  - ?

PMID- 28444670
TI  - ?

PMID- 28444671
TI  - ?

PMID- 28444672
TI  - ?

PMID- 28444674
TI  - ?

PMID- 28444673
TI  - ?

PMID- 28444675
TI  - ?

PMID- 28444676
TI  - [Associated Injuries in Radial Head Fractures].
AB  - Purpose Radial head fractures, particularly Mason I and II, are considered
      "harmless" injuries, and their severity is underestimated. In recent years,
      associated injuries to ligaments, cartilage, and adjacent bones have been studied
      in more detail. This meta-analysis collects the data on their incidence from the
      current literature. Methods A systematic review of the online databases PubMed,
      EMBASE, CINAHL and Cochrane Library was performed to identify clinical studies on
      associated injuries in radial head fracture. Their incidence was assessed as
      weighted means and broken down into Mason types. The clinical relevance of these
      injuries was not primarily assessed, but all available data were collected.
      Results Data on 1323 patients (48 % female) were extracted from 11 studies. 66 %
      had a Mason I, 21 % a Mason II, and 13 % a Mason III injury. In 33 % of all
      patients, associated injuries were found. The most common injury was damage to
      the lateral collateral ligaments (51 %), the second most common to the capitellum
      (22 %). 82 % of the Mason III fractures had associated injuries, compared to 36 %
      in Mason II, and 15 % in Mason I. Data on the clinical relevance of these
      injuries showed a rate of 11 % of persisting complaints requiring further
      treatment. Conclusions Associated injuries with radial head fractures are more
      frequent, and need treatment more frequently, than commonly assumed. Even in
      "harmless" Mason I fractures, severe associated injuries requiring surgical
      treatment are frequent. For clinical practice, persisting pain, even in a
      "simple" Mason I injury, should lead to a timely, specialised assessment and
      treatment.

PMID- 28444677
TI  - [Deformity Correction in Skeletally Immature Patients - Therapy].

PMID- 28444678
TI  - Pyelonephritis in Pregnancy: Prediction of Prolonged Hospitalization and Maternal
      Morbidity using Prognostic Scoring Systems.

PMID- 28444679
TI  - Membranes derived from human umbilical cord Wharton's jelly stem cells as novel
      bioengineered tissue-like constructs.
AB  - Cell-derived matrices were recently described as novel biomaterials generated by
      human cells allowed to grow and synthetize their own extracellular matrix in
      culture. In the present work, we generated and evaluated a novel tissue-like
      substitute (WDM) consisting of a membrane derived from cultured human Wharton's
      jelly stem cells. WDM were evaluated ex vivo and in vivo by histochemistry and
      immunohistochemistry for several mesenchymal cell markers and fibrillar and non
      fibrillar extracellular matrix components. Results show that WDM were
      heterogeneous and consisted of dense cell-poor areas surrounded by cell-rich
      zones with abundant HWJSC. Histological analyses demonstrated that cell-poor
      areas were very rich in fibrillar and non-fibrillar extracellular matrix
      components such as collagen and proteoglycans, and cells in the WDM were highly
      viable and mostly PCNA-positive. HWJSC in the WDM expressed all markers of this
      cell type, including CD90, CD105, pan cytokeratin and CK8. In vivo analysis
      showed that the WDM was highly biocompatible and grafting this membrane in the
      muscle of laboratory rats was not associated to increased inflammation, necrosis,
      tumorigenesis or other side effects, while cells properly integrated at the
      damage site and showed high proliferation index. These results suggest that the
      structure and composition of the extracellular matrix of these novel WDM could
      reproduce the situation of native human tissues and that WDM implanted in vivo
      are highly biocompatible and rapidly integrate in the host tissues. For these
      reasons, we hypothesize that WDM could be used in regenerative medicine
      protocols.

PMID- 28444680
TI  - [Disability after stroke: a longitudinal study in moderate and severe stroke
      patients included in a multidisciplinary rehabilitation program].
AB  - INTRODUCTION: Stroke is a recognized cause of disability among adults. However
      the impact that the deficits that occur after a moderate/severe stroke have on
      long-term disability, as well as the response of the resultant deficits to
      rehabilitation, are not completely understood. PATIENTS AND METHODS: A total of
      396 patients with a modified Rankin score >= 3 after an ischemic (n = 221) or
      hemorrhagic (n = 175) stroke were included in this study. All patients were
      assessed with cognitive, behavior, emotional, motor and functional domains. All
      patients were assessed at baseline and six months after inclusion in a
      multidisciplinary rehabilitation program. RESULTS: Risk of falling (Berg Balance
      Scale < 45 in 83.1% of the sample at baseline and 49.5% at follow-up) and
      functional problems (82.8% with a Barthel Index < 75 at baseline and 53% at
      follow-up) were the most prevalent deficits. Emotional disturbances were those
      that most improved while behavioral problems were those that did less. Although
      global disability improved during treatment among most patients, only 11% of our
      patients, especially those with preserved cognitive function at baseline, could
      be classified as patients with mild disability at follow-up. CONCLUSIONS: Stroke
      consequences are multidimensional. The symptoms that the stroke can cause in
      multiple domains, as well as the pattern of recovery are widely diverse, with
      prevalence of behavioral long-term disturbances.

PMID- 28444681
TI  - [Wolf-Hirschhorn syndrome. Description of a Spanish cohort of 51 cases and a
      literature review].
AB  - INTRODUCTION: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome that
      gives rise to multiple congenital anomalies, caused by the loss of a distal
      portion of the short arm of chromosome 4 (4p16.3). It is characterised by its own
      peculiar facial phenotype, associated to growth problems, psychomotor retardation
      and epilepsy. AIMS: To establish a register of patients with WHS in Spain,
      describe their characteristics, determine the prevalence of epilepsy, estimate
      the degree of psychomotor retardation and perform a review of the literature in
      order to compare these data with those published to date. PATIENTS AND METHODS:
      In collaboration with the Spanish Wolf-Hirschhorn Syndrome Association, we
      contacted the families affected and collected data via forms endorsed by medical
      reports. RESULTS: The characteristics of 51 patients are described. Psychomotor
      retardation was considered the most severe in 37% of cases. Of the total sample,
      88% presented epilepsy, and nearly all of them showed growth problems. The mean
      size of the deletion was 8.4 Mb, and the phenotype is displayed in photographs.
      Other clinical features reported were sensory alterations and nephrourological
      and cardiological pathologies. CONCLUSIONS: This study reports on the second
      largest cohort of patients with WHS with a genetic characterisation published to
      date. Many of the characteristics coincide with those described previously, with
      several exceptions, such as the degree of psychomotor retardation, which appears
      to be lower in the sample studied here.

PMID- 28444682
TI  - [Transcultural validation in Spanish of the Actionable Bladder Symptoms Screening
      Tool].
AB  - INTRODUCTION: Disorders of the lower urinary tract are frequent in patients with
      multiple sclerosis throughout the course of the disease and reach variable
      prevalences close to 75%. It is essential to obtain an early diagnosis in the
      initial phases and to implement an optimal therapeutic management. Burks et al
      developed the Actionable Bladder Symptoms Screening Tool (ABSST) as a useful
      screening test in such disorders. Later, Bates et al developed a short version of
      the ABSST with the objective of minimising the time required to complete it and
      making it easier to use. AIMS: To carry out the transcultural validation into
      Spanish of the short version of the ABSST. PATIENTS AND METHODS: The ABSST was
      translated into Spanish and then back-translated into English, which confirmed
      the semantic equivalence. A field test was conducted on 40 patients with multiple
      sclerosis, with two extra questions being included at the end in order to check
      the comprehension and acceptability of the tool, together with a final item that
      asked for the time spent on completing it. RESULTS: Forty patients were selected
      In accordance with the eligibility and exclusion criteria; 67.5% of them were
      females and the overall mean age was 46.2 years. The rate of comprehension of the
      test was 100%, and that of acceptability was 97.5%. Results showed that 57.5%
      obtained scores >= 3, and an average of 5.33 minutes were spent on completing it.
      CONCLUSIONS: As a brief screening questionnaire for urinary disorders in multiple
      sclerosis, the ABSST is a useful tool for detecting them at an early stage and
      has now been validated for use in Spanish.

PMID- 28444683
TI  - [Atypical Guillain-Barre syndrome clustering: is it necessary to reconsider the
      diagnostic criteria and microbiological protocol?]
AB  - INTRODUCTION: Guillain-Barre syndrome is classically defined as a symmetrical
      ascending acute polyradiculoneuropathy, although there are atypical variants that
      make diagnosis difficult. CASE REPORTS: The medical data of six patients in our
      hospital area are collected during the first quarter of 2013. Lumbar punctures,
      imaging, neurophysiological studies, ganglioside antibodies and serologies have
      been proposed in all cases. We focus on the atypical features as late
      hyporeflexia, increased frequency of asymmetry and distal paresis and initial
      fever. From a neurophysiological point of view, all patients presented
      sensorimotor axonal forms. The most consistent datas in early studies is the F
      wave's alteration. A Miller Fisher variant associated with faciocervicobraquial
      paresis and cerebral reversible vasoconstriction syndrome has been detected. A
      bilateral brachial paresis and lumbar polyradiculopathy in the context of
      influenza A infection is other interesting case. The saltatory variant with
      cranial nerve involvement and lower limbs paresis has been demonstrated in one
      patient. Bands in cerebrospinal fluid are positive in three cases and anti
      ganglioside antibodies in one patient. The syndrome of inappropriate secretion of
      antidiuretic hormone may explain some of the hyponatremias registered. The first
      line of treatment are inmunoglobulins in all patients. Plasmapheresis exchanges
      has been used as an additional therapy in four cases. CONCLUSIONS: These clusters
      of six axonal cases with atypical clinical features justifies the need for
      knowledge of these variants in order to achieve an early treatment. Late
      hyporeflexia and brachialfaciocervico, saltatory and lumbar forms should be
      considered in the spectrum of Guillain-Barre syndrome. The etiological study
      should rule out a lots of pathogens as influenza A.

PMID- 28444685
TI  - [II Congreso Regional / XVII Reunion Anual de la Sociedad Murciana de Neurologia.
      Communications].

PMID- 28444684
TI  - [Evaluation and treatment of sleep problems in children diagnosed with attention
      deficit hyperactivity disorder: an update of the evidence].
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) affects
      approximately 5% of all children and adolescents, and these patients frequently
      suffer from sleep problems. The association between sleep disorders and ADHD,
      however, is multifaceted and complex. AIMS: To explore the relationship between
      sleep disorders and ADHD. DEVELOPMENT: Sleep problems in children with ADHD
      include altered sleep and specific disorders per se or that may be due to
      comorbid psychiatric disorders or to the stimulants they receive as treatment for
      their ADHD. Today, an evaluation of the sleep conditions in children with ADHD is
      recommended before starting pharmacological treatment. The first step in managing
      their sleep problems is good sleep hygiene and cognitive-behavioural
      psychotherapy. Another option is to consider modifying the dosage and formulation
      of the stimulants. Atomoxetine and melatonin are therapeutic alternatives for
      children with ADHD and more severe sleep problems. Specific treatments exist for
      respiratory and movement disorders during sleep. CONCLUSIONS: It is important to
      evaluate sleep in children who present symptoms suggestive of ADHD, since
      problems during sleep can play a causal role or exacerbate the clinical features
      of ADHD. Correct evaluation and treatment of sleep disorders increase the
      family's and the child's quality of life and can lessen the severity of the
      symptoms of ADHD.

PMID- 28444686
TI  - [Association between myasthenia gravis and systemic lupus erythematosus: is it
      safe to use hydroxychloroquine?]

PMID- 28444688
TI  - Semiparametric estimation of the accelerated failure time model with partly
      interval-censored data.
AB  - Partly interval-censored (PIC) data arise when some failure times are exactly
      observed while others are only known to lie within certain intervals. In this
      article, we consider efficient semiparametric estimation of the accelerated
      failure time (AFT) model with PIC data. We first generalize the Buckley-James
      estimator for right-censored data to PIC data. Then, we develop a one-step
      estimator by deriving and estimating the efficient score for the regression
      parameters. We show that under mild regularity conditions the generalized Buckley
      James estimator is consistent and asymptotically normal and the one-step
      estimator is consistent and asymptotically normal with a covariance matrix that
      attains the semiparametric efficiency bound. We conduct extensive simulation
      studies to examine the performance of the proposed estimators in finite samples
      and apply our methods to data derived from an AIDS study.

PMID- 28444687
TI  - Creutzfeldt-Jakob disease lookback study: 21 years of surveillance for
      transfusion transmission risk.
AB  - BACKGROUND: Transfusion transmission of human prion diseases has been observed
      for variant Creutzfeldt-Jakob disease (vCJD), but not for the classic forms of
      prion disease (CJD: sporadic, genetic, and iatrogenic). Although the presence of
      prions or misfolded prion proteins in blood has been documented in some patients
      with the most common form of CJD, sporadic CJD, no transfusion-transmitted cases
      of CJD have been recognized. Since 1995, the American Red Cross has conducted a
      lookback study of the recipients of blood products from donors who develop CJD to
      assess the risk of blood-borne CJD transmission in the United States. STUDY
      DESIGN AND METHODS: Blood donors subsequently diagnosed with confirmed or
      probable CJD were enrolled and the consignees were asked to identify the
      recipients of their blood products. These donors' transfusion recipients are
      traced annually with the National Death Index to see if they subsequently die of
      CJD. RESULTS: To date, 65 CJD donors have been enrolled along with 826 of their
      blood recipients. These recipients have contributed 3934 person-years of follow
      up and no transfusion-transmitted cases of CJD have been recognized. CONCLUSION:
      From this study, as well as other epidemiologic studies, there is no evidence of
      CJD transfusion transmission; this risk remains theoretical.

PMID- 28444689
TI  - The Young's Modulus, Fracture Stress, and Fracture Strain of Gellan Hydrogels
      Filled with Whey Protein Microparticles.
AB  - Texture modifying abilities of whey protein microparticles are expected to be
      dependent on pH during heat-induced aggregation of whey protein in the
      microparticulation process. Therefore, whey protein microparticles were prepared
      at either pH 5.5 or 6.8 and their effects on small and large deformation
      properties of gellan gels containing whey protein microparticles as fillers were
      investigated. The majority of whey protein microparticles had diameters around 2
      MUm. Atomic force microscopy images showed that whey protein microparticles
      prepared at pH 6.8 partially collapsed and flatted by air-drying, while those
      prepared at pH 5.5 did not. The Young's modulus of filled gels adjusted to pH 5.5
      decreased by the addition of whey protein microparticles, while those of filled
      gels adjusted to pH 6.8 increased with increasing volume fraction of filler
      particles. These results suggest that filler particles were weakly bonded to gel
      matrices at pH 5.5 but strongly at pH 6.8. Whey protein microparticles prepared
      at pH 5.5 showed more enhanced increases in the Young's modulus than those
      prepared at pH 6.8 at volume fractions between 0.2 and 0.4, indicating that
      microparticles prepared at pH 5.5 were mechanically stronger. The fracture stress
      of filled gels showed trends somewhat similar to those of the Young's modulus,
      while their fracture strains decreased by the addition of whey protein
      microparticles in all examined conditions, indicating that the primary effect of
      these filler particles was to enhance the brittleness of filled gels.

PMID- 28444690
TI  - Strobilurins as growth-promoting compounds: how Stroby regulates Arabidopsis leaf
      growth.
AB  - Strobilurins are an important class of agrochemical fungicides used throughout
      the world on a wide variety of crops as protection against fungal pathogens. In
      addition to this protective role, they are reported to also positively influence
      plant physiology. In this study, we analysed the effect of Stroby(r) WG, a
      commercially available fungicide consisting of 50% (w/w) kresoxim-methyl (KM) as
      active strobilurin compound, on Arabidopsis leaf growth. Treatment of seedlings
      with Stroby resulted in larger leaves due to an increase in cell number.
      Transcriptome analysis of Stroby-treated rosettes demonstrated an increased
      expression of genes involved in redox homeostasis, iron metabolism and sugar
      transport. Stroby treatment strongly induced the expression of the subgroup Ib
      basic helix-loop-helix (bHLH) transcription factors, which have a role in iron
      homeostasis under iron-limiting conditions. Single loss-of-function mutants of
      three bHLHs and their triple bhlh039, bhlh100 and bhlh101 mutant did not respond
      to Stroby treatment. Although iron and sucrose content was not affected, nitric
      oxide (NO) levels and nitrate reductase (NR) activity were significantly
      increased in Stroby-treated rosettes as compared with control plants. In
      conclusion, we suggest that the Stroby-mediated effects on growth depend on the
      increased expression of the subgroup Ib bHLHs and higher NO levels.

PMID- 28444691
TI  - MALDI-MS profiling of serum O-glycosylation and N-glycosylation in COG5-CDG.
AB  - Congenital disorders of glycosylation (CDG) are due to defective glycosylation of
      glycoconjugates. Conserved oligomeric Golgi (COG)-CDG are genetic diseases due to
      defects of the COG complex subunits 1-8 causing N-glycan and O-glycan processing
      abnormalities. In COG-CDG, isoelectric focusing separation of undersialylated
      glycoforms of serum transferrin and apolipoprotein C-III (apoC-III) allows to
      detect N-glycosylation and O-glycosylation defects, respectively. COG5-CDG (COG5
      subunit deficiency) is a multisystem disease with dysmorphic features,
      intellectual disability of variable degree, seizures, acquired microcephaly,
      sensory defects and autistic behavior. We applied matrix-assisted laser
      desorption/ionization-MS for a high-throughput screening of differential serum O
      glycoform and N-glycoform in five patients with COG5-CDG. When compared with age
      matched controls, COG5-CDG showed a significant increase of apoC-III0a
      (aglycosylated glycoform), whereas apoC-III1 (mono-sialylated glycoform)
      decreased significantly. Serum N-glycome of COG5-CDG patients was characterized
      by the relative abundance of undersialylated and undergalactosylated biantennary
      and triantennary glycans as well as slight increase of high-mannose structures
      and hybrid glycans. Using advanced and well-established MS-based approaches, the
      present findings reveal novel aspects on O-glycan and N-glycan profiling in COG5
      CDG patients, thus providing an increase of current knowledge on glycosylation
      defects caused by impairment of COG subunits, in support of clinical diagnosis.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444692
TI  - A profile likelihood approach for longitudinal data analysis.
AB  - Inappropriate choice of working correlation structure in generalized estimating
      equations (GEE) could lead to inefficient parameter estimation while impractical
      normality assumption in likelihood approach would limit its applicability in
      longitudinal data analysis. In this article, we propose a profile likelihood
      method for estimating parameters in longitudinal data analysis via maximizing the
      estimated likelihood. The proposed method yields consistent and efficient
      estimates without specifications of the working correlation structure nor the
      underlying error distribution. Both theoretical and simulation results confirm
      the satisfactory performance of the proposed method. We illustrate our
      methodology with a diastolic blood pressure data set.

PMID- 28444693
TI  - A Tiered Approach to Evaluating Salinity Sources in Water at Oil and Gas
      Production Sites.
AB  - A suspected increase in the salinity of fresh water resources can trigger a site
      investigation to identify the source(s) of salinity and the extent of any
      impacts. These investigations can be complicated by the presence of naturally
      elevated total dissolved solids or chlorides concentrations, multiple potential
      sources of salinity, and incomplete data and information on both naturally
      occurring conditions and the characteristics of potential sources. As a result,
      data evaluation techniques that are effective at one site may not be effective at
      another. In order to match the complexity of the evaluation effort to the
      complexity of the specific site, this paper presents a strategic tiered approach
      that utilizes established techniques for evaluating and identifying the source(s)
      of salinity in an efficient step-by-step manner. The tiered approach includes:
      (1) a simple screening process to evaluate whether an impact has occurred and if
      the source is readily apparent; (2) basic geochemical characterization of the
      impacted water resource(s) and potential salinity sources coupled with simple
      visual and statistical data evaluation methods to determine the source(s); and
      (3) advanced laboratory analyses (e.g., isotopes) and data evaluation methods to
      identify the source(s) and the extent of salinity impacts where it was not
      otherwise conclusive. A case study from the U.S. Gulf Coast is presented to
      illustrate the application of this tiered approach.

PMID- 28444694
TI  - Outcomes of acute kidney injury in a department of internal medicine in ABIDJAN
      (cote D'IVOIRE).
AB  - AIM: To investigate the prognostic factors of acute kidney injury (AKI) in our
      daily practice. METHODS: We analyzed the cohort of patients hospitalized for AKI
      in the period from January 2010 to December 2015 in the Department of Internal
      Medicine, University Hospital of Treichville. Kaplan-Meier curves were built for
      survival analysis. Cox regression analysis was used to identify independent
      predictors of mortality. RESULTS: We collected 414 cases of AKI during the study
      period. The mean age was 48.3 +/- 16.8 years. We observed a male predominance
      with a sex ratio (236/178) of 1.32. In multivariate analysis, the predictive
      factors of death were age >= 65 years (HR = 2.13; 95% CI = 1.28-3.55; P = 0.004),
      AKI stage 3 (HR = 1.69; 95%CI = 1.13-2.50; P = 0.009), haemoglobin <8 g/dL (HR =
      2.91; 95% CI = 1.79-4.72; P = 0.0001), infection (HR = 1.85; 95% CI = 1.21-2.83;
      P = 0.004) and drug-induced AKI (HR = 3.23; 95% CI = 1.65-6.29; P = 0.001).
      Factors associated with incomplete recovery or non-recovery of renal function
      beyond 3 months were age >= 65 years (OR = 4.76; 95% CI = 1.85-12.50;P = 0.001),
      hypertension (OR = 2.17; 95% CI = 1.07-4.34; P = 0.03), haemoglobin <8 g/dL (OR =
      6.66; 95% CI = 2.94-8.28; P < 0.001), AKI stage 3 (OR = 9.09; 95% CI = 4.54
      16.66; P < 0.001) malignant hypertension (OR = 5; 95% CI = 1.67-7.27; P = 0.005)
      and cancer (OR = 4.69; 95% CI = 2.22-6.63; P = 0.001). CONCLUSION: The
      aetiologies are dominated by infections. The fatality rate is high and its risk
      factors are advanced age, low haemoglobin level, severe AKI, infection and drug
      intake. Prevention is essential.

PMID- 28444696
TI  - Self-Assembly of Luminescent Lanthanide Mesocates as Efficient Catalysts for
      Transforming Carbon Dioxide into Cyclic Carbonates.
AB  - Four dinuclear lanthanide mesocates were fabricated through a spontaneous self
      assembly method, and the formation of these complexes was well studied by their
      absorption and emission spectra. These stable complexes were also found to
      exhibit superior performance in catalyzing the coupling reaction between epoxides
      and CO2 with excellent recyclability. Moreover, the catalysts could be prepared
      on large scale. Moreover, the Yb and Lu complexes featured emissions in the near
      infrared and visible regions, respectively, and their intensities and lifetimes
      could be used for identification purposes. Thus, this new approach can be used to
      construct promising lanthanide complexes as efficient catalysts and it identifies
      the possibility to better study a catalytic reaction with a luminescent catalyst.

PMID- 28444695
TI  - Exercise therapy for chronic fatigue syndrome.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent,
      medically unexplained fatigue, as well as symptoms such as musculoskeletal pain,
      sleep disturbance, headaches and impaired concentration and short-term memory.
      CFS presents as a common, debilitating and serious health problem. Treatment may
      include physical interventions, such as exercise therapy, which was last reviewed
      in 2004. OBJECTIVES: The objective of this review was to determine the effects of
      exercise therapy (ET) for patients with CFS as compared with any other
      intervention or control.* Exercise therapy versus 'passive control' (e.g.
      treatment as usual, waiting-list control, relaxation, flexibility).* Exercise
      therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT),
      cognitive treatment, supportive therapy, pacing, pharmacological therapy such as
      antidepressants).* Exercise therapy in combination with other specified treatment
      strategies versus other specified treatment strategies (e.g. exercise combined
      with pharmacological treatment vs pharmacological treatment alone). SEARCH
      METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis
      Controlled Trials Register (CCDANCTR), the Cochrane Central Register of
      Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive
      list of free-text terms for CFS and exercise. We located unpublished or ongoing
      trials through the World Health Organization (WHO) International Clinical Trials
      Registry Platform (to May 2014). We screened reference lists of retrieved
      articles and contacted experts in the field for additional studies SELECTION
      CRITERIA: Randomised controlled trials involving adults with a primary diagnosis
      of CFS who were able to participate in exercise therapy. Studies had to compare
      exercise therapy with passive control, psychological therapies, adaptive pacing
      therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review
      authors independently performed study selection, risk of bias assessments and
      data extraction. We combined continuous measures of outcomes using mean
      differences (MDs) and standardised mean differences (SMDs). We combined serious
      adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall
      effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS:
      We have included eight randomised controlled studies and have reported data from
      1518 participants in this review. Three studies diagnosed individuals with CFS
      using the 1994 criteria of the Centers for Disease Control and Prevention (CDC);
      five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven
      studies used variations of aerobic exercise therapy such as walking, swimming,
      cycling or dancing provided at mixed levels in terms of intensity of the aerobic
      exercise from very low to quite rigorous, whilst one study used anaerobic
      exercise. Control groups consisted of passive control (eight studies; e.g.
      treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive
      therapy (one study), supportive listening (one study), pacing (one study),
      pharmacological treatment (one study) and combination treatment (one study). Risk
      of bias varied across studies, but within each study, little variation was found
      in the risk of bias across our primary and secondary outcome
      measures.Investigators compared exercise therapy with 'passive' control in eight
      trials, which enrolled 971 participants. Seven studies consistently showed a
      reduction in fatigue following exercise therapy at end of treatment, even though
      the fatigue scales used different scoring systems: an 11-item scale with a
      scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148
      participants; low-quality evidence); the same 11-item scale with a scoring system
      of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540
      participants; moderate-quality evidence); and a 14-item scale with a scoring
      system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152
      participants; moderate-quality evidence). Serious adverse reactions were rare in
      both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate
      quality evidence), but sparse data made it impossible for review authors to draw
      conclusions. Study authors reported a positive effect of exercise therapy at end
      of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies,
      323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five
      studies, 725 participants) and self-perceived changes in overall health (RR 1.83,
      95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for
      review authors to draw conclusions regarding the remaining outcomes.Investigators
      compared exercise therapy with CBT in two trials (351 participants). One trial
      (298 participants) reported little or no difference in fatigue at end of
      treatment between the two groups using an 11-item scale with a scoring system of
      0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences
      in fatigue at follow-up, but neither found differences between the two groups
      using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30,
      95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring
      system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse
      reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed
      little or no difference in physical functioning, depression, anxiety and sleep,
      and we were not able to draw any conclusions with regard to pain, self-perceived
      changes in overall health, use of health service resources and drop-out rate.With
      regard to other comparisons, one study (320 participants) suggested a general
      benefit of exercise over adaptive pacing, and another study (183 participants) a
      benefit of exercise over supportive listening. The available evidence was too
      sparse to draw conclusions about the effect of pharmaceutical interventions.
      AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less
      fatigued following exercise therapy, and no evidence suggests that exercise
      therapy may worsen outcomes. A positive effect with respect to sleep, physical
      function and self-perceived general health has been observed, but no conclusions
      for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and
      health service resources were possible. The effectiveness of exercise therapy
      seems greater than that of pacing but similar to that of CBT. Randomised trials
      with low risk of bias are needed to investigate the type, duration and intensity
      of the most beneficial exercise intervention.

PMID- 28444698
TI  - Radiofrequency exposure levels in Amsterdam schools.

PMID- 28444699
TI  - Design, Synthesis, and Chemistry of Bis(sigma)borate and Agostic Complexes of
      Group 7 Metals.
AB  - A series of new bis(sigma)borate and agostic complexes of group 7 metals have
      been synthesized and structurally characterized from various borate ligands, such
      as trihydrobis(benzothiazol-2-yl)amideborate (Na[(H3 B)bbza]), trihydro(2
      aminobenzothiazolyl)borate (Na[(H3 B)abz]), and dihydrobis(2
      mercaptopyridyl)borate (Na[(H2 B)mp2 ]) (bbza=bis(benzothiazol-2-yl)amine, abz=2
      aminobenzothiazolyl, and mp=2-mercaptopyridyl). Photolysis of [Mn2 (CO)10 ] with
      Na[(H3 B)bbza] formed bis(sigma)borate complex [Mn(CO)3 (MU-H)2 BHNCSC6 H4 (NR)]
      (1; R=NCSC6 H4 ). Octahedral complex [Re(CO)2 (N3 C2 S2 C12 H8 )2 ] (2) was
      generated under similar reaction conditions with [Re2 (CO)10 ]. Similarly, when
      [Mn2 (CO)10 ] was treated with Na[(H3 B)abz], bis(sigma)borate complex [Mn(CO)3
      (MU-H)2 BH(HN2 CSC6 H4 )] (3) and the agostic complex [Mn(CO)3 (MU-H)BH(HN2 CSC6
      H4 )2 ] (4) were formed. To probe the potential formation of agostic complexes of
      the heavier group 7 metals, we carried out the photolysis of [M2 (CO)10 ] with
      Na[(H2 B)mp2 ] and found that [M(CO)3 (MU-H)BH(C5 H4 NS)2 ] (5: M=Re; 6: M=Mn)
      was formed in moderate yield. Complexes 1 and 3 feature a (kappa3 -H,H,N)
      coordination mode, whereas 4, 5, and 6 display both (kappa3 -H,N,N) and (kappa3 
      H,S,S) modes of the corresponding ligands. To investigate the lability of the CO
      ligands of 1 and 3, we treated the complexes with phosphine ligands that
      generated novel bis(sigma)borate complexes [Mn(MU-H)2 (BHNCSC6 H4 )(NR)(CO)2 PL2
      L'] (R=NCSC6 H4 ; 7 a: L=L'=Ph; 7 b: L=Ph, L'=Me) and [Mn(MU-H)2 BHN(NCSC6 H4
      )R(CO)2 PL2 L'] (R=NCSC6 H4 ; 8 a: L=L'=Ph; 8 b: L=Ph, L'=Me). Complexes 7 and 8
      are structural isomers with different coordination modes of the bbza ligand. In
      addition, DFT calculations were performed to shed some light on the bonding and
      electronic structures of these complexes.

PMID- 28444697
TI  - Population Pharmacokinetics of Dexmedetomidine in Infants.
AB  - Despite limited pharmacokinetic (PK) data, dexmedetomidine is increasingly being
      used off-label for sedation in infants. We aimed to characterize the
      developmental PK changes of dexmedetomidine during infancy. In this open-label,
      single-center PK study of dexmedetomidine in infants receiving dexmedetomidine
      per clinical care, <=10 blood samples per infant were collected. A set of
      structural PK models and residual error models were explored using nonlinear
      mixed-effects modeling in NONMEM. Covariates including postmenstrual age (PMA),
      serum creatinine, and recent history of cardiac surgery requiring cardiopulmonary
      bypass were investigated for their influence on PK parameters. Univariable
      generalized estimating equation models were used to evaluate the association of
      hypotension with dexmedetomidine concentrations. A total of 89 PK samples were
      collected from 20 infants with a median PMA of 44 weeks (range, 33-61). The
      median maximum dexmedetomidine infusion dose during the study period was 1.8
      MUg/(kg.h) (0.5-2.5), and 16/20 infants had a maximum dose >1 MUg/(kg.h). A 1
      compartment model best described the data. Younger PMA was a significant
      predictor of lower clearance. Infants with a history of cardiac surgery had ~40%
      lower clearance compared to those without a history of cardiac surgery. For
      infants with PMA of 33 to 61 weeks and body weight of 2 to 6 kg, the estimated
      clearance and volume of distribution were 0.87 to 2.65 L/(kg.h) and 1.5 L/kg,
      respectively. No significant associations were found between dexmedetomidine
      concentrations and hypotension. Infants with younger PMA and recent cardiac
      surgery may require relatively lower doses of dexmedetomidine to achieve exposure
      similar to older patients and those without cardiac surgery.

PMID- 28444700
TI  - Fluorescence-Lifetime Imaging and Super-Resolution Microscopies Shed Light on the
      Directed- and Self-Assembly of Functional Porphyrins onto Carbon Nanotubes and
      Flat Surfaces.
AB  - Functional porphyrins have attracted intense attention due to their remarkably
      high extinction coefficients in the visible region and potential for optical and
      energy-related applications. Two new routes to functionalised SWNTs have been
      established using a bulky ZnII -porphyrin featuring thiolate groups at the
      periphery. We probed the optical properties of this zinc(II)-substituted, bulky
      aryl porphyrin and those of the corresponding new nano-composites with single
      walled carbon nanotube (SWNTs) and coronene, as a model for graphene. We report
      hereby on: i) the supramolecular interactions between the pristine SWNTs and ZnII
      -porphyrin by virtue of pi-pi stacking, and ii) a novel covalent binding strategy
      based on the Bingel reaction. The functional porphyrins used acted as dispersing
      agent for the SWNTs and the resulting nanohybrids showed improved dispersibility
      in common organic solvents. The synthesized hybrid materials were probed by
      various characterisation techniques, leading to the prediction that
      supramolecular polymerisation and host-guest functionalities control the
      fluorescence emission intensity and fluorescence lifetime properties. For the
      first time, XPS studies highlighted the differences in covalent versus non
      covalent attachments of functional metalloporphyrins to SWNTs. Gas-phase DFT
      calculations indicated that the ZnII -porphyrin interacts non-covalently with
      SWNTs to form a donor-acceptor complex. The covalent attachment of the porphyrin
      chromophore to the surface of SWNTs affects the absorption and emission
      properties of the hybrid system to a greater extent than in the case of the
      supramolecular functionalisation of the SWNTs. This represents a synthetic
      challenge as well as an opportunity in the design of functional nanohybrids for
      future sensing and optoelectronic applications.

PMID- 28444701
TI  - Is electrolyte transfer across the urothelium important?: ICI-RS 2015.
AB  - AIMS: This article summarizes discussion at the International Consultation on
      Incontinence Research Society (ICI-RS) 2015 meeting of urine modification in the
      urinary tract by the urothelium. It considers the literature and proposes
      pertinent questions that need to be addressed to understand this phenomenon
      within a physiological context. METHODS: Following the ICI-RS meeting,
      publications in PubMed relating to urine modification in the renal pelvis,
      ureter, and bladder were reviewed. RESULTS: Historically, the urothelium has been
      simply considered as a passive, impermeable barrier, preventing contact between
      urine and the underlying cells. In addition to the ability of the umbrella cells
      to modify the surface area of the urothelium during bladder filling, the
      urothelium may also be involved in modifying urine composition. Several lines of
      evidence support the hypothesis that electrolytes and water can be reabsorbed by
      the urothelium and that this may have physiological relevance. Firstly,
      urothelial cells express several types of aquaporins and ion channels; the
      membrane expression of which is modulated by the extracellular concentration of
      ions including Na+ . Secondly, studies of urine composition in the renal pelvis
      and bladder demonstrate urine modification, indicating that water and/or
      electrolyte transport has occurred. Thirdly, hibernating mammals, with urothelial
      and bladder wall histology similar to non-hibernating mammals are known to
      produce and reabsorb urine daily, during long periods of hibernation.
      CONCLUSIONS: The phenomenon of urine modification by the urothelium may be
      physiologically important during normal bladder filling. Research should be
      focused on investigating how this may change in conditions of urinary
      dysfunction.

PMID- 28444702
TI  - The role of male slings in post prostatectomy incontinence: ICI-RS 2015.
AB  - AIMS: Post prostatectomy stress urinary incontinence can significantly impact on
      quality of life and is bothersome for patients. The artificial urinary sphincter
      is still considered the gold standard surgical treatment. Male slings are an
      alternative surgical option and several designs are currently available. This
      review will focus on efficacy, adverse events, and mechanism of action of male
      slings. The context of this review was a proposal at the ICI-RS meeting 2015.
      Following synthesis of the evidence we address the question: does it matter how
      male slings work? METHODS: The proposal lecture was reviewed and a comprehensive
      review of the literature undertaken utilising the PubMed database. RESULTS: Male
      slings can be broadly divided into adjustable retropubic and suburethral
      transobturator slings. Male slings are efficacious and can improve quality of
      life. Adjustable retropubic slings appear to be compressive but studies suggest
      efficacy can be achieved without voiding dysfunction. Transobturator slings work
      by urethral compression and/or re-locating the urethral bulb. There is a
      recognized failure rate in all sling types and most studies suggest radiotherapy
      as a risk factor for failure. Adjustable slings have the ability to be altered to
      optimize continence or to prevent retention of urine. However, there appears to
      be a higher explantation rate in some of these systems. CONCLUSIONS: It is
      important to understand how male slings work and by doing so we are more reliably
      able to choose the appropriate sling, predict outcomes, and as a result counsel
      patients. Suggestions for future research are proposed.

PMID- 28444703
TI  - How does lower urinary tract dysfunction affect sexual function in men and women?
      ICI-RS 2015-Part 1.
AB  - AIM: The aim of this paper is to review the literature on the effect of lower
      urinary tract symptoms (LUTS) on sexual function and dysfunction. METHODS: At the
      International Consultation on Incontinence-Research Society (ICI-RS) in 2015, a
      multidisciplinary group presented a literature search of what is known about the
      effect of lower urinary tract dysfunction (LUTD) on sexual function (SF) in men
      and women. Wider discussions regarding knowledge gaps and ideal research
      methodology ensued. RESULTS: A body of evidence supports associations between
      LUTS/urinary incontinence on SF in both men and women, but the true prevalence of
      the impact of LUTD on SF remains largely unknown. There is still reluctance among
      health care professionals (HCP's) to discuss SF with patients and often patients
      who are not asked will not volunteer their problems. CONCLUSION: A significant
      knowledge gap in this area remains. Education among HCP's on assessment and
      treatment of sexual dysfunction and communication skills are essential to
      encourage, and engage patients with HCP's. Neurourol. Urodynam. 36:949-952, 2017.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28444704
TI  - How does lower urinary tract dysfunction (LUTD) affect sexual function in men and
      women? ICI-RS 2015-Part 2.
AB  - AIM: To discuss available data on the links between LUTD and sexual dysfunction,
      what is still unknown about the causative effect of disease processes on sexual
      function (SF), and to suggest proposals for further research. METHODS: At the
      2015 International Consultation on Incontinence-Research Society (ICI-RS), a
      multi-disciplinary group presented a literature search of what is known about the
      effect of LUTD on SF in men and women. Wider discussions regarding knowledge
      gaps, and ideal research methodology ensued and are presented. RESULTS: The
      underlying mechanisms of the impact of LUTD on SF remain largely unknown. Risk
      factors for the metabolic syndrome may cause both LUTS and ED in men, and their
      improvement may improve both conditions. In women, neurovascular changes may be
      common in LUTD and FSD. Successful LUTS management results in FSD improvement,
      but the mechanisms are ill understood. Gaps in standardization of sexual
      dysfunction terminology, variations of assessment, and treatment in clinical
      practice and research make most studies not comparable. The sensitive knowledge
      and subjective nature of the problem present challenges and often result in
      neglecting it. CONCLUSION: Neurovascular and hormonal factors, but also indirect
      effects may link LUTD to SD in both sexes, but the evidence is not robust and the
      mechanisms unclear. There is a need for defining the terminology and
      standardizing outcomes assessed in clinical trials. The multifactorial nature of
      SF in both sexes makes trial design challenging and "real world" studies may
      prove more beneficial for patients' outcomes and clinicians' understanding.

PMID- 28444705
TI  - Under what circumstances should stress incontinence surgery be performed at the
      same time as prolapse surgery? ICI-RS 2015.
AB  - AIMS: An International Consultation on Incontinence-Research Society (ICI-RS)
      Think Tank in 2015 discussed and evaluated the evidence of when stress
      incontinence surgery should be performed with prolapse surgery and highlighted
      evidence gaps, with the aim of recommending further clinical and research
      proposals. METHODS: A review of the literature assessing randomized studies where
      women with vaginal prolapse have been randomized to vaginal prolapse surgery with
      or without continence surgery were evaluated. The different clinical
      presentations were also evaluated and their impact on outcome was critically
      reviewed. RESULTS: There are three symptomatic groups of women with vaginal
      prolapse who are treated. The first group is continent women with vaginal
      prolapse. The second group has stress urinary incontinence (SUI) and vaginal
      prolapse. The last group has vaginal prolapse and have been found through testing
      to have occult SUI. The studies have reported a range of outcomes for each of
      these groups. There are different outcomes based on the surgical method used to
      correct the prolapse and also the different continence surgical techniques. There
      are insufficient studies to allow firm conclusions to be drawn. The economic
      impact of the different management pathways is also discussed although costs vary
      according to different national medical funding systems. CONCLUSIONS: There is
      considerable uncertainty about the optimal method of managing women with vaginal
      prolapse and stress incontinence due to the different surgical techniques
      available. In particular the group of women with occult SUI are a challenge as
      the optimal diagnostic method has not yet been defined.

PMID- 28444706
TI  - Adolescents with nocturnal enuresis and daytime urinary incontinence-How can
      pediatric and adult care be improved-ICI-RS 2015?
AB  - AIMS: Nocturnal enuresis (NE) and daytime urinary incontinence (DUI) are common
      in adolescents. The aim of this paper was to review studies on prevalence,
      clinical symptoms and associated risk factors and to formulate recommendations
      for assessment and treatment. MATERIALS AND METHODS: A systematic Scopus search
      was performed and relevant publications were selected. The topic was discussed
      during the ICI-RS meeting in 2015. RESULTS: One to two percent of older
      adolescents are affected by NE and 1% by DUI. NE and DUI are associated with
      multiple risk factors such as fecal incontinence and constipation, obesity,
      chronic illness, and psychological impairment. Chronic treatment-resistant,
      relapsing and new-onset cases can occur. Adolescent NE and DUI can be treated by
      a multidisciplinary team according to pediatric principles. Additional treatment
      components have been developed for adolescents. Transition from pediatric to
      adult services is frequently disorganized. CONCLUSIONS: Incontinence in
      adolescents is a neglected research topic and clinical care is often suboptimal.
      As adolescents are seen by both pediatric and adult services, alignment and
      harmonization of diagnostic and therapeutic principles is needed. Also, an
      organized transition process is recommended to improve care for adolescent
      patients. Neurourol. Urodynam. 36:843-849, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28444707
TI  - Editorial.

PMID- 28444708
TI  - Can we create a valid treatment algorithm for patients with drug resistant
      overactive bladder (OAB) syndrome or detrusor overactivity (DO)? Results from a
      think tank (ICI-RS 2015).
AB  - AIMS: To review and assess the definitions of drug resistance and the evidence
      supporting treatment for drug resistant overactive bladder/detrusor overactivity
      (OAB/DO). METHODS: Evidence review of the extant literature and consensus of
      opinion was used to derive the summary recommendations. RESULTS: Drug resistance
      or drug refractory status has been inconsistently defined and reported in current
      evident sources. Recent publications use some correlation of lack of efficacy and
      or experienced side effects to define drug resistance. Algorithms based upon
      these definitions largely relate to the appropriate use of neuromodulation or
      botulinum neurotoxin, based upon patient selection and patient choice. Current
      treatment pathways are hampered by inability to consistently profile patients to
      optimize management, particularly after failure of initial pragmatic treatment.
      CONCLUSIONS: Further research is recommended to better identify patient phenotype
      for purposes of directing optimized therapy for OAB/DO. Current treatment
      algorithms are influenced by extensive data generated from recent neuromodulation
      and botulinum neurotoxin trials.

PMID- 28444709
TI  - Male bladder outlet obstruction: Time to re-evaluate the definition and
      reconsider our diagnostic pathway? ICI-RS 2015.
AB  - The diagnosis of bladder outlet obstruction (BOO) in the male is dependent on
      measurements of pressure and flow made during urodynamic studies. The procedure
      of urodynamics and the indices used to delineate BOO are well standardized
      largely as a result of the work of the International Continence Society. The
      clinical utility of the diagnosis of BOO is however, less well defined and there
      are several shortcomings and gaps in the currently available medical literature.
      Consequently the International Consultation on Incontinence Research Society (ICI
      RS) held a think tank session in 2015 entitled "Male bladder outlet obstruction:
      Time to re-evaluate the definition and reconsider our diagnostic pathway?" This
      manuscript details the discussions that took place within that think tank setting
      out the pros and cons of the current definition of BOO and exploring alternative
      clinical tests (alone or in combination) which may be useful in the future
      investigation of male patients with lower urinary tract symptoms. The think tank
      panel concluded that pressure-flow studies remain the diagnostic gold-standard
      for BOO although there is still a lack of high quality evidence. Newer, less
      invasive, investigations have shown promise in terms of diagnostic accuracy for
      BOO but similar criticisms can be levelled against these tests. Therefore, the
      think tank suggests further research with regard to these alternative indicators
      to determine their clinical utility.

PMID- 28444710
TI  - Can we define and characterize the aging lower urinary tract?-ICI-RS 2015.
AB  - The prevalence of lower urinary tract (LUT) symptoms increases with age but the
      etiology is unknown. This article aims to identify research directions that
      clarify the basis of this association. The initial question is whether biological
      age is the variable of interest or a time-dependent accumulation of factors that
      impact on LUT function at rates that differ between individuals. In particular,
      the accumulation of conditions or agents due to inflammatory states or tissue
      ischemia is important. Much of the above has been concerned with changes to
      bladder function and morphology. However, the outflow tract function is also
      affected, in particular changes to the function of external sphincter skeletal
      muscle and associated sacral motor nerve control. Nocturia is a cardinal symptom
      of LUT dysfunction and is more prevalent with aging. Urine production is
      determined by diurnal changes to the production of certain hormones as well as
      arterial blood pressure and such diurnal rhythms are blunted in subjects with
      nocturia, but the causal links remain to be elucidated. Changes to the central
      nervous control of LUT function with age are also increasingly recognized,
      whether in mid-brain/brainstem regions that directly affect LUT function or in
      higher centers that determine psycho-social and emotional factors impinging on
      the LUT. In particular, the linkage between increasing white matter
      hyperintensities and LUT dysfunction during aging is recognized but not
      understood. Overall, a more rational approach is being developed to link LUT
      dysfunction with factors that accumulate with age, however, the precise causal
      pathways remain to be characterized. Neurourol. Urodynam. 36:854-858, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28444711
TI  - Are we justified in suggesting change to caffeine, alcohol, and carbonated drink
      intake in lower urinary tract disease? Report from the ICI-RS 2015.
AB  - AIMS: There is increasing evidence that diet may have a significant role in the
      development of lower urinary tract symptoms. While fluid intake is known to
      affect lower urinary tract function the effects of alcohol, caffeine, carbonated
      drinks, and artificial sweeteners are less well understood and evidence from
      epidemiological studies is mixed and sometimes contradictory. The aim of this
      paper is to appraise the available evidence on the effect of caffeine, alcohol,
      and carbonated drinks on lower urinary tract function and dysfunction in addition
      to suggesting proposals for further research. METHODS: Literature review based on
      a systematic search strategy using the terms "fluid intake," "caffeine,"
      "alcohol," "carbonated" and "urinary incontinence," "detrusor overactivity,"
      "Overactive Bladder," "OAB." RESULTS: In addition to fluid intake, there is some
      evidence to support a role of caffeine, alcohol, and carbonated beverages in the
      pathogenesis of OAB and lower urinary tract dysfunction. Although some findings
      are contradictory, others clearly show an association between the ingestion of
      caffeine, carbonated drinks, and alcohol with symptom severity. CONCLUSIONS Given
      the available evidence lifestyle interventions and fluid modification may have an
      important role in the primary prevention of lower urinary tract symptoms.
      However, more research is needed to determine the precise role of caffeine,
      carbonated drinks, and alcohol in the pathogenesis and management of these
      symptoms. The purpose of this paper is to stimulate that research. Neurourol.
      Urodynam. 36:876-881, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28444712
TI  - The urinary microbiome and its contribution to lower urinary tract symptoms; ICI
      RS 2015.
AB  - AIMS: The microbiome is the term used for the symbiotic microbial colonisation of
      healthy organs. Studies have found bacterial identifiers within voided urine
      which is apparently sterile on conventional laboratory culture, and accordingly
      there may be health and disease implications. METHODS: The International
      Consultation on Incontinence Research Society (ICI-RS) established a literature
      review and expert consensus discussion focussed on the increasing awareness of
      the urinary microbiome, and potential research priorities. RESULTS: The consensus
      considered the discrepancy between findings of conventional clinical microbiology
      methods, which generally rely on culture parameters predisposed towards certain
      "expected" organisms. Discrepancy between selective culture and RNA sequencing to
      study species-specific 16S ribosomal RNA is increasingly clear, and highlights
      the possibility that protective or harmful bacteria may be overlooked where
      microbiological methods are selective. There are now strong signals of the
      existence of a "core" urinary microbiome for the human urinary tract,
      particularly emerging with ageing. The consensus reviewed the potential
      relationship between a patient's microbiome and lower urinary tract dysfunction,
      whether low-count bacteriuria may be clinically significant and mechanisms which
      could associate micro-organisms with lower urinary tract symptoms. CONCLUSIONS:
      Key research priorities identified include the need to establish the scope of
      microbiome across the range of normality and clinical presentations, and gain
      consensus on testing protocols. Proteomics to study enzymatic and other functions
      may be necessary, since different bacteria may have overlapping phenotype.
      Longitudinal studies into risk factors for exposure, cumulative risk, and
      emergence of disease need to undertaken. Neurourol. Urodynam. 36:850-853, 2017.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28444713
TI  - Do we assess urethral function adequately in LUTD and NLUTD? ICI-RS 2015.
AB  - INTRODUCTION: Urethral function, as well as anatomy, play a significant role in
      voiding reflex and abnormalities in one or both contribute to the pathophysiology
      of Lower Urinary Tract Dysfunction (LUTD). We have several diagnostic tools to
      assess the urethral function or dysfunction but the question remains, are these
      adequate? METHODS: This is a report of the proceedings of Think Tank P1: 'Do we
      assess urethral function adequately in LUTD and NLUTD?' from the annual
      International Consultation on Incontinence-Research Society, which took place
      September 22-24, 2014 in Bristol, UK. RESULTS: We have collected and discussed,
      as a committee, the evidence with regard to the urethra and the available
      relevant methods of testing urethral function, with the emphasis on female and
      male voiding dysfunction. We looked into previous research and clinical studies
      and compiled summaries of pertinent testing related to urethral function. The
      discussion has focused on clinical applications and the desirability of further
      development of functional tests and analyses in this field. CONCLUSIONS: There
      are limitations to most of the urethral function tests. Future perspectives and
      research should concentrate on further development of functional testing and
      imaging techniques with emphasis on standardization and clinical application of
      these tests. Neurourol. Urodynam. 36:935-942, 2017. (c) 2017 Wiley Periodicals,
      Inc.

PMID- 28444714
TI  - Is testosterone important in LUT function in men and women? ICI-RS 2015.
AB  - AIM: This review article is a collaborative report based upon the Authors'
      presentations and Group discussion on the role of testosterone (T) in the male
      and female lower urinary tract (LUT) which took place at the 6th International
      Consultation on Incontinence Research Society's (ICI-RS) annual meeting, in
      Bristol, UK (September 8-10, 2015). METHODS: It comprises overviews and opinions
      on both the current state of knowledge of the role of T in LUT function and
      dysfunction in both sexes. RESULTS: Results from animal studies suggest that T
      treatment may be beneficial for disorders of the LUT in women including urinary
      incontinence and pelvic organ prolapse. The need for clinical studies to evaluate
      the effect of T treatment in peri- and post-menopausal women, taking into account
      the type of applied androgen, the application form, timing and dosage, is
      especially emphasized. In males, findings on the impact of T on the male external
      urethral sphincter underscores that there is still much to learn about its role
      in male LUT physiology. The important topic of the use of T therapy in the
      treatment of enuresis in the young, both sexes, is also discussed. The importance
      of understanding the steroidogenic pathways linking T with estradiol is discussed
      as being of paramount importance in researching the unique actions of T in the
      LUT. CONCLUSION: The overall conclusion is that further research into the role of
      T in LUT function and dysfunction across genders and age groups (young to old) is
      extremely important. Neurourol. Urodynam. 36:859-862, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28444715
TI  - Can a patient reported outcome be adequate without assessing quality of life in
      lower urinary tract dysfunction?
AB  - AIMS AND METHODS: A think tank was convened at the sixth ICI-RS meeting held in
      the United Kingdom on September 2015, to consider the adequacy of patient
      reported outcome (PRO) measurement if quality of life (QoL) evaluation were
      excluded. Rigorous methodology is proposed for the development of PROs and much
      is written about this process but the necessity for QoL inclusion is rarely
      discussed. The decision was therefore taken to consider what QoL evaluation
      provides and what these data provide. RESULTS: Discussions highlighted the need
      to question our aim for including QoL evaluation in clinical practice and
      research, in order to ensure its necessity for the intended purpose. Improved
      understanding of the usefulness of QoL data, in particular in relation to
      important health indicators was also identified as an area of unmet need.
      CONCLUSIONS: The think tank ended with a collaborative research proposal to pool
      existing QoL databases to explore the correlations with other outcome measures
      and types of associations present. It was suggested that these findings would
      enable clinicians and researchers to make more informed decisions regarding PRO
      selection, use, and intepretation.

PMID- 28444716
TI  - The Relative Bioavailability of Ibuprofen After Administration With a Novel Soft
      Chewable Drug Formulation.
AB  - The first aim of the present study was to evaluate the bioavailability of
      ibuprofen dispersed in a novel soft chewable formulation compared with a
      traditional ibuprofen tablet; its second was to map the quality of taste masking
      and patient product satisfaction. In a phase 1, single-center, open-label,
      randomized, crossover study, healthy subjects received a soft-chew formulation or
      a hard tablet (reference), both containing 100 mg ibuprofen. Serial blood samples
      were collected over 24 hours to assess ibuprofen bioavailability. Taste and
      satisfaction after chewing the novel formulation 3 or 8 times were evaluated with
      a questionnaire. The soft-chew formulation showed comparable bioavailability to
      the reference tablet. The highest peak plasma concentration was observed after 3
      chews, and the relative bioavailability was approximately 8% higher compared to 8
      chews. The overall flavor was well appreciated, and chewing 3 times was
      significantly preferred (P = .043) over chewing 8 times. Soft chewable drug
      formulations may improve compliance and potentially benefit several
      subpopulations who experience dysphagia.

PMID- 28444718
TI  - Erratum.

PMID- 28444719
TI  - What's in this issue.

PMID- 28444717
TI  - Effect of Donor Strength and Bulk on Thieno[3,4-b]-pyrazine-Based Panchromatic
      Dyes in Dye-Sensitized Solar Cells.
AB  - Near-infrared-absorbing organic dyes are critically needed in dye-sensitized
      solar cells (DSCs). Thieno[3,4-b]pyrazine (TPz) based dyes can access the NIR
      spectral region and show power conversion efficiencies (PCEs) of up to 8.1 % with
      sunlight being converted at wavelengths up to 800 nm for 17.6 mA cm-2 of
      photocurrent in a co-sensitized DSC device. Precisely controlling dye excited
      state energies is critical for good performances in NIR DSCs. Strategies to
      control TPz dye energetics with stronger donor groups and TPz substituent choice
      are evaluated here. Additionally, donor size influence versus dye loading on TPz
      dyes is analyzed with respect to the TiO2 surface protection designed to prevent
      recombination of electrons in TiO2 with the redox shuttle. Importantly, the dyes
      evaluated were demonstrated to work well with low Li+ concentration electrolytes,
      with iodine and cobalt redox shuttle systems, and efficiently as part of co
      sensitized devices.

PMID- 28444720
TI  - 32nd Annual BACCN Conference.

PMID- 28444721
TI  - BACCN clinically commissioned papers.

PMID- 28444722
TI  - Are you interested in joining the BACCN national board?

PMID- 28444723
TI  - BACCN Twitter chats.

PMID- 28444724
TI  - The morality of good end-of-life care in critical care.

PMID- 28444725
TI  - Expressions of Interest in joining Oral Care consensus group.

PMID- 28444726
TI  - Regional news and events.

PMID- 28444727
TI  - Advances in understanding the pathogenesis of familial myeloproliferative
      neoplasms.
AB  - Myeloproliferative neoplasms (MPNs) are generally acquired as a result of a
      somatic stem cell mutation leading to clonal expansion of myeloid precursors. In
      addition to sporadic cases, familial MPN occurs when one or several MPN affect
      different relatives of the same family. MPN driver mutations (JAK2, CALR, MPL)
      are somatically acquired also in familial cases, so a genetic predisposition to
      acquire one of the MPN driver mutations would be inherited, even though the
      causative germline mutations underlying familial MPN remain largely unknown.
      Recently some germline variants [ATG2B and GSKIP duplication, RBBP6 mutations,
      SH2B3 (LNK) mutations], which can cause familial MPN, have been reported but
      these mutations are rare and do not explain most familial cases. Patients with
      familial MPN show the same clinical features and suffer the same complications as
      those with sporadic disease. This review aims to offer up-to-date information
      regarding the genetics of familial MPN.

PMID- 28444730
TI  - Ruxolitinib as a promising treatment for corticosteroid-refractory graft-versus
      host disease.

PMID- 28444729
TI  - Benefits of rituximab as a second-line treatment for autoimmune haemolytic
      anaemia in children: a prospective French cohort study.
AB  - Childhood autoimmune haemolytic anaemia (AIHA) requires second-line
      immunosuppressive therapy in 30-50% of cases. It appears that rituximab is
      indicated in such circumstances. This prospective national study reports the
      practice, efficacy and tolerance of rituximab in children with isolated AIHA and
      AIHA in the setting of Evans syndrome (ES). Sixty-one children were given
      rituximab between 2000 and 2014. The median interval from diagnosis to rituximab
      was 9.9 [interquartile range (IQR) 1.6-28.5] months. Forty-six patients responded
      (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients
      relapsed at a median interval of 10.8 (IQR 3.9-18.7) months, rituximab allowed
      steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete
      response and 6-year RFS were significantly higher than in ES (P < 0.05). Ten out
      of 61 patients were infants, seven of who responded with a 6-year RFS of 71%.
      Among patients without immunoglobulin substitution before rituximab, 4 are still
      receiving substitutions. Five patients died, including one potentially
      attributable to rituximab. This large observational series of childhood AIHA
      established the rituximab benefit-risk ratio, allowing steroid withdrawal, with
      37% of long-term responders, mainly in isolated AIHA. All subgroups of patients
      drew benefit. Our long-term results indicate the baseline to be challenged by new
      treatment approaches.

PMID- 28444728
TI  - Circulating cell-free BRAFV600E as a biomarker in children with Langerhans cell
      histiocytosis.
AB  - The BRAFV600E mutation is reported in half of patients with Langerhans cell
      histiocytosis (LCH). This study investigated the detection of the BRAFV600E
      allele in circulating cell-free (ccf) DNA in a paediatric LCH cohort. Children
      with BRAFV600E -mutated LCH were investigated to detect ccf BRAFV600E at
      diagnosis (n = 48) and during follow-up (n = 17) using a picolitre-droplet
      digital PCR assay. At diagnosis, ccf BRAFV600E was positive in 15/15 (100%)
      patients with risk-organ positive multisystem (RO+ MS) LCH, 5/12 (42%) of
      patients with RO- MS LCH and 3/21 (14%) patients with single-system (SS) LCH (P <
      0.001, Fisher's exact test). The positive BRAFV600E load was higher for RO+
      patients (mean, 2.90%; range, 0.04-11.4%) than for RO- patients (mean, 0.16%;
      range, 0.01-0.39) (P = 0.003, Mann-Whitney U test). After first-line vinblastine
      steroid induction therapy, 7/7 (100%) of the non-responders remained positive for
      ccf BRAFV600E compared to 2/4 (50%) of the partial-responders and 0/4 of the
      complete responders (P = 0.002, Fisher's exact test). Six children treated with
      vemurafenib showed a clinical response that was associated with a decrease in the
      ccf BRAFV600E load at day 15. Thus, ccf BRAFV600E is a promising biomarker for
      monitoring the response to therapy for children with RO+ MS LCH or RO- LCH
      resistant to first-line chemotherapy.

PMID- 28444732
TI  - Low back pain among nurses in Slovenian hospitals: cross-sectional study.
AB  - AIM: The study investigated the prevalence and factors predicting low back pain
      among nurses in Slovenian hospitals. BACKGROUND: The risk factors for low back
      pain are physical and psychosocial. Implementation of interventions for reducing
      low back pain calls for management support, accessible equipment, education,
      knowledge and risk assessment. INTRODUCTION: Low back pain prevalence and
      incidence among healthcare workers is very high compared to the general
      population and is a strong risk factor for long-term sickness absence. METHODS: A
      cross-sectional study design was utilized. We used validated instruments: Nordic
      Musculoskeletal Disorder Questionnaire, Stanford Presenteeism Scale and Perceived
      Stress Scale. The sample included 1744 nursing employees from 16 Slovenian
      hospitals, ranging from practical nurses, registered nurses, nurses with a
      bachelor's degree and those with a master's degree. FINDINGS: Results revealed a
      prevalence of low back pain among 85.9% of respondents. Relevant risk factors
      included female gender, age, length of employment, years in current position,
      shift work and the number of nurses per shift. In the regression model, factors
      predicting low back pain included presenteeism with a negative effect on work,
      presenteeism and maintaining work productivity, inability to control daily life,
      number of nurses per shift and respondents' age. CONCLUSIONS: Future activities
      should be oriented towards eliminating or reducing risks for low back pain
      incidents and towards different strategies, guidelines and actions which empower
      individuals and provide knowledge to manage and prevent low back pain.
      IMPLICATIONS FOR MANAGEMENT AND HEALTH POLICY: Slovenian healthcare system
      planning needs a national strategy to successfully promote LBP preventive and
      controlling strategies. Management can plan preventive and curative measures to
      reduce low back pain prevalence among nursing personnel. Management should also
      implement policies reflecting research findings.

PMID- 28444733
TI  - Hybridization increases mitochondrial production of reactive oxygen species in
      sunfish.
AB  - Mitochondrial dysfunction and oxidative stress have been suggested to be possible
      mechanisms underlying hybrid breakdown, as a result of mito-nuclear
      incompatibilities in respiratory complexes of the electron transport system.
      However, it remains unclear whether hybridization increases the production of
      reactive oxygen species (ROS) by mitochondria. We used high-resolution
      respirometry and fluorometry on isolated liver mitochondria to examine
      mitochondrial physiology and ROS emission in naturally occurring hybrids of
      pumpkinseed (Lepomis gibbosus) and bluegill (L. macrochirus). ROS emission was
      greater in hybrids than in both parent species when respiration was supported by
      complex I (but not complex II) substrates, and was associated with increases in
      lipid peroxidation. However, respiratory capacities for oxidative
      phosphorylation, phosphorylation efficiency, and O2  kinetics in hybrids were
      intermediate between those in parental species. Flux control ratios of capacities
      for electron transport (measured in uncoupled mitochondria) relative to oxidative
      phosphorylation suggested that the limiting influence of the phosphorylation
      system is reduced in hybrids. This likely helped offset impairments in electron
      transport capacity and complex III activity, but contributed to augmenting ROS
      production. Therefore, hybridization can increase mitochondrial ROS production,
      in support of previous suggestions that mitochondrial dysfunction can induce
      oxidative stress and thus contribute to hybrid breakdown.

PMID- 28444734
TI  - Highly electronegative low-density lipoprotein L5 evokes microglial activation
      and creates a neuroinflammatory stress via Toll-like receptor 4 signaling.
AB  - Atherogenic risk factors, such as hypercholesterolemia, are associated with
      increased risk of neurodegeneration, especially Alzheimer's dementia. Human
      plasma electronegative low-density lipoprotein [LDL(-)], especially L5, may serve
      as an important contributing factor. L5 promoting an inflammatory action in
      atherosclerosis has been extensively studied. However, the role of L5 in inducing
      neuroinflammation remains unknown. Here, we examined the impact of L5 on immune
      activation and cell viability in cultured BV-2 microglia. BV-2 cells treated with
      lipopolysaccharide or human LDLs (L1, L5, or oxLDL) were subjected to
      molecular/biochemical assays for measuring microglial activation, levels of
      inflammatory factors, and cell survival. A transwell BV-2/N2a co-culture was used
      to assess N2a cell viability following BV-2 cell exposure to L5. We found that L5
      enables the activation of microglia and elicits an inflammatory response, as
      evidenced by increased oxygen/nitrogen free radicals (nitric oxide, reactive
      oxygen species, and peroxides), elevated tumor necrosis factor-alpha levels,
      decreased basal interleukin-10 levels, and augmented production of pro
      inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2). L5
      also triggered BV-2 cell death primarily via apoptosis. These effects were
      markedly disrupted by the application of signaling pathway inhibitors, thus
      demonstrating that L5 interacts with Toll-like receptor 4 to modulate multiple
      pathways, including MAPKs, PI3K/Akt, and NF-kappaB. Decreased N2a cell viability
      in a transwell co-culture was mainly ascribed to L5-induced BV-2 cell activation.
      Together, our data suggest that L5 creates a neuroinflammatory stress via
      microglial Toll-like receptor 4, thereby leading to the death of BV-2 microglia
      and coexistent N2a cells. Atherogenic L5 possibly contributes to
      neuroinflammation-related neurodegeneration.

PMID- 28444735
TI  - From genetic single candidate gene studies to complex genomics of GvHD.
AB  - Graft-versus-host disease (GvHD) is a serious complication affecting the
      recipients of allogeneic haematopoietic stem cells. In this present review we
      attempt to summarize the current knowledge on the effect of the donor and
      recipient genotypes on GvHD, starting from human leucocyte antigen (HLA) matching
      for an optimal donor selection, typing of non-classical HLA and minor
      histocompatibility antigens through the polymorphic variations in genes coding
      for non-HLA proteins contributing to the development of GvHD and response to
      treatment. The results of recent Candidate Gene Studies (CGS) and Genome-Wide
      Association Studies (GWAS) are presented and discussed.

PMID- 28444736
TI  - Selective progesterone receptor modulators (SPRMs) for uterine fibroids.
AB  - BACKGROUND: Uterine fibroids are smooth muscle tumours arising from the uterus.
      These tumours, although benign, are commonly associated with abnormal uterine
      bleeding, bulk symptoms and reproductive dysfunction. The importance of
      progesterone in fibroid pathogenesis supports selective progesterone receptor
      modulators (SPRMs) as effective treatment. Both biochemical and clinical evidence
      suggests that SPRMs may reduce fibroid growth and ameliorate symptoms. SPRMs can
      cause unique histological changes to the endometrium that are not related to
      cancer, are not precancerous and have been found to be benign and reversible.
      This review summarises randomised trials conducted to evaluate the effectiveness
      of SPRMs as a class of medication for treatment of individuals with fibroids.
      OBJECTIVES: To evaluate the effectiveness and safety of SPRMs for treatment of
      premenopausal women with uterine fibroids. SEARCH METHODS: We searched the
      Specialised Register of the Cochrane Gynaecology and Fertility Group, the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase,
      PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL)
      and clinical trials registries from database inception to May 2016. We
      handsearched the reference lists of relevant articles and contacted experts in
      the field to request additional data. SELECTION CRITERIA: Included studies were
      randomised controlled trials (RCTs) of premenopausal women with fibroids who were
      treated for at least three months with a SPRM. DATA COLLECTION AND ANALYSIS: Two
      review authors independently reviewed all eligible studies identified by the
      search. We extracted data and assessed risk of bias independently using standard
      forms. We analysed data using mean differences (MDs) or standardised mean
      differences (SMDs) for continuous data and odds ratios (ORs) for dichotomous
      data. We performed meta-analyses using the random-effects model. Our primary
      outcome was change in fibroid-related symptoms. MAIN RESULTS: We included in the
      review 14 RCTs with a total of 1215 study participants. We could not extract
      complete data from three studies. We included in the meta-analysis 11 studies
      involving 1021 study participants: 685 received SPRMs and 336 were given a
      control intervention (placebo or leuprolide). Investigators evaluated three
      SPRMs: mifepristone (five studies), ulipristal acetate (four studies) and
      asoprisnil (two studies). The primary outcome was change in fibroid-related
      symptoms (symptom severity, health-related quality of life, abnormal uterine
      bleeding, pelvic pain). Adverse event reporting in the included studies was
      limited to SPRM-associated endometrial changes. More than half (8/14) of these
      studies were at low risk of bias in all domains. The most common limitation of
      the other studies was poor reporting of methods. The main limitation for the
      overall quality of evidence was potential publication bias. SPRM versus placebo
      SPRM treatment resulted in improvements in fibroid symptom severity (MD -20.04
      points, 95% confidence interval (CI) -26.63 to -13.46; four RCTs, 171 women, I2 =
      0%; moderate-quality evidence) and health-related quality of life (MD 22.52
      points, 95% CI 12.87 to 32.17; four RCTs, 200 women, I2 = 63%; moderate-quality
      evidence) on the Uterine Fibroid Symptom Quality of Life Scale (UFS-QoL, scale 0
      to 100). Women treated with an SPRM showed reduced menstrual blood loss on
      patient-reported bleeding scales, although this effect was small (SMD -1.11, 95%
      CI -1.38 to -0.83; three RCTs, 310 women, I2 = 0%; moderate-quality evidence),
      along with higher rates of amenorrhoea (29 per 1000 in the placebo group vs 237
      to 961 per 1000 in the SPRM group; OR 82.50, 95% CI 37.01 to 183.90; seven RCTs,
      590 women, I2 = 0%; moderate-quality evidence), compared with those given
      placebo. We could draw no conclusions regarding changes in pelvic pain owing to
      variability in the estimates. With respect to adverse effects, SPRM-associated
      endometrial changes were more common after SPRM therapy than after placebo (OR
      15.12, 95% CI 6.45 to 35.47; five RCTs, 405 women, I2 = 0%; low-quality
      evidence). SPRM versus leuprolide acetate In comparing SPRM versus other
      treatments, two RCTs evaluated SPRM versus leuprolide acetate. One RCT reported
      primary outcomes. No evidence suggested a difference between SPRM and leuprolide
      groups for improvement in quality of life, as measured by UFS-QoL fibroid symptom
      severity scores (MD -3.70 points, 95% CI -9.85 to 2.45; one RCT, 281 women;
      moderate-quality evidence) and health-related quality of life scores (MD 1.06
      points, 95% CI -5.73 to 7.85; one RCT, 281 women; moderate-quality evidence). It
      was unclear whether results showed a difference between SPRM and leuprolide
      groups for reduction in menstrual blood loss based on the pictorial blood loss
      assessment chart (PBAC), as confidence intervals were wide (MD 6 points, 95% CI 
      40.95 to 50.95; one RCT, 281 women; low-quality evidence), or for rates of
      amenorrhoea (804 per 1000 in the placebo group vs 732 to 933 per 1000 in the SPRM
      group; OR 1.14, 95% CI 0.60 to 2.16; one RCT, 280 women; moderate-quality
      evidence). No evidence revealed differences between groups in pelvic pain scores
      based on the McGill Pain Questionnaire (scale 0 to 45) (MD -0.01 points, 95% CI 
      2.14 to 2.12; 281 women; moderate-quality evidence). With respect to adverse
      effects, SPRM-associated endometrial changes were more common after SPRM therapy
      than after leuprolide treatment (OR 10.45, 95% CI 5.38 to 20.33; 301 women;
      moderate-quality evidence). AUTHORS' CONCLUSIONS: Short-term use of SPRMs
      resulted in improved quality of life, reduced menstrual bleeding and higher rates
      of amenorrhoea than were seen with placebo. Thus, SPRMs may provide effective
      treatment for women with symptomatic fibroids. Evidence derived from one RCT
      showed no difference between leuprolide acetate and SPRM with respect to improved
      quality of life and bleeding symptoms. Evidence was insufficient to show whether
      effectiveness was different between SPRMs and leuprolide. Investigators more
      frequently observed SPRM-associated endometrial changes in women treated with
      SPRMs than in those treated with placebo or leuprolide acetate. As noted above,
      SPRM-associated endometrial changes are benign, are not related to cancer and are
      not precancerous. Reporting bias may impact the conclusion of this meta-analysis.
      Well-designed RCTs comparing SPRMs versus other treatments are needed.

PMID- 28444737
TI  - Digest: Know your poison: Predictable molecular changes confer toxin resistance
      in snakes.

PMID- 28444739
TI  - Incidence and survival trends in mantle cell lymphoma.

PMID- 28444738
TI  - Factors influencing biased agonism in recombinant cells expressing the human
      alpha1A -adrenoceptor.
AB  - BACKGROUND AND PURPOSE: Agonists acting at GPCRs promote biased signalling via
      Galpha or Gbetagamma subunits, GPCR kinases and beta-arrestins. Since the
      demonstration of biased agonism has implications for drug discovery, it is
      essential to consider confounding factors contributing to bias. We have examined
      bias at human alpha1A -adrenoceptors stably expressed at low levels in CHO-K1
      cells, identifying off-target effects at endogenous receptors that contribute to
      ERK1/2 phosphorylation in response to the agonist oxymetazoline. EXPERIMENTAL
      APPROACH: Intracellular Ca2+ mobilization was monitored in a Flexstation(r) using
      Fluo 4-AM. The accumulation of cAMP and ERK1/2 phosphorylation were measured
      using AlphaScreen(r) proximity assays, and mRNA expression was measured by RT
      qPCR. Ligand bias was determined using the operational model of agonism. KEY
      RESULTS: Noradrenaline, phenylephrine, methoxamine and A61603 increased Ca2+
      mobilization, cAMP accumulation and ERK1/2 phosphorylation. However,
      oxymetazoline showed low efficacy for Ca+2 mobilization, no effect on cAMP
      generation and high efficacy for ERK1/2 phosphorylation. The apparent functional
      selectivity of oxymetazoline towards ERK1/2 was related to off-target effects at
      5-HT1B receptors endogenously expressed in CHO-K1 cells. Phenylephrine and
      methoxamine showed genuine bias towards ERK1/2 phosphorylation compared to Ca2+
      and cAMP pathways, whereas A61603 displayed bias towards cAMP accumulation
      compared to ERK1/2 phosphorylation. CONCLUSION AND IMPLICATIONS: We have shown
      that while adrenergic agonists display bias at human alpha1A -adrenoceptors, the
      marked bias of oxymetazoline for ERK1/2 phosphorylation originates from off
      target effects. Commonly used cell lines express a repertoire of endogenous GPCRs
      that may confound studies on biased agonism at recombinant receptors.

PMID- 28444740
TI  - Chronic lymphocytic leukaemia genomics and the precision medicine era.
AB  - Massive genomic analyses have underscored the diversity of chronic lymphocytic
      leukaemia (CLL) between patients. Genetic heterogeneity of tumour clones within a
      patient may fuel tumour evolution. Several recurrently deregulated intra-cellular
      pathways are candidates for targeted therapies that are very promising and are
      dramatically changing clinical patients' perspectives. In this review we present
      an overview of the genetic and epigenetic features of CLL and their clinical and
      biological implications.

PMID- 28444741
TI  - Haem augments and iron chelation decreases toll-like receptor 4 mediated
      inflammation in monocytes from sickle cell patients.

PMID- 28444742
TI  - The effect of rituximab on anti-platelet autoantibody levels in patients with
      immune thrombocytopenia.
AB  - Rituximab is an effective therapy resulting in a platelet count improvement in
      60% of patients with immune thrombocytopenia (ITP). Rituximab depletes B cells;
      thus, a reduction in platelet autoantibody levels would be anticipated in
      patients who achieve a clinical response to this treatment. The objectives of
      this study were to determine whether rituximab was associated with a reduction in
      platelet autoantibody levels, and to correlate the loss of autoantibodies with
      the achievement of a treatment response. We performed a case-control study nested
      within a previous randomized controlled trial of standard therapy plus adjuvant
      rituximab or placebo. We measured platelet-bound anti-glycoprotein (GP) IIbIIIa
      and anti-GPIbIX using the antigen capture test. Of 55 evaluable patients, 25
      (45%) had a detectable platelet autoantibody at baseline. Rituximab was
      associated with a significant reduction in anti-GPIIbIIIa levels (P = 0.02) but
      not anti-GPIbIX levels (P = 0.51) compared with placebo. Neither the presence of
      an autoantibody at baseline nor the loss of the autoantibody after treatment was
      associated with a response to rituximab. The subset of patients with persistent
      autoantibodies after treatment failed to achieve a platelet count response,
      suggesting that persistence of platelet autoantibodies can be a marker of disease
      severity.

PMID- 28444743
TI  - Systemic lupus erythematosus with Degos disease: role of dermatoscopy in
      diagnosis.

PMID- 28444745
TI  - Retraction: 'Dose-dependent dual effect of HTLV-1 tax oncoprotein on p53
      dependent nucleotide excision repair in human T-cells' by Yana Schavinsky
      Khrapunsky, Esther Priel and Mordechai Aboud.
AB  - : The above article, published online on 4 October 2007 in Wiley Online Library
      (wileyonlinelibrary.com), and in Volume 122, pp. 305-316, has been retracted by
      agreement between the journal Editor in Chief, Professor Peter Lichter, and John
      Wiley & Sons Ltd. The retraction has been agreed as the bands in Figs 1, 2, 5 and
      6 appear to have been manipulated. REFERENCE: Schavinsky-Khrapunsky, Y., Priel,
      E. and Aboud, M. (2008), Dose-dependent dual effect of HTLV-1 tax oncoprotein on
      p53-dependent nucleotide excision repair in human T-cells. Int. J. Cancer, 122:
      305-316. doi:10.1002/ijc.23091.

PMID- 28444746
TI  - Response to "A randomized controlled trial of the ketogenic diet in refractory
      childhood epilepsy".

PMID- 28444744
TI  - Dual cyclin-dependent kinase 4/6 inhibition by PD-0332991 induces apoptosis and
      senescence in oesophageal squamous cell carcinoma cells.
AB  - BACKGROUND AND PURPOSE: Aberrant activation of the cyclin D1-cyclin-dependent
      kinase 4/6 (CDK4/6)-Rb signalling pathway is common in oesophageal squamous cell
      carcinoma (ESCC). PD-0332991, a highly specific inhibitor of CDK4/6, has potent
      antitumour activity against many types of cancer. The purpose of this study was
      to examine the in vitro and in vivo antineoplastic effect of PD-0332991 against
      the growth and metastasis of ESCC cells. EXPERIMENTAL APPROACH: Cell viability
      and any synergy between PD-0332991 and 5-fluorouracil or cisplatin were measured
      by MTS assay and CalcuSyn software respectively. Cell migration and invasion were
      detected by wound healing and transwell assays. Apoptosis was evaluated by flow
      cytometry after staining annexin V-FITC/PI. Cellular senescence was assessed by
      measuring SA-beta-gal activity. Nude mouse xenograft models of ESCC were employed
      to determine the in vivo activity of PD-0332991 against tumour growth and lung
      metastasis. KEY RESULTS: PD-0332991 inhibited cellular growth and induced
      mitochondrial-dependent apoptosis in ESCC cells. PD-0332991 also suppressed
      migration, invasion and the expression of MMP-2 in ESCC cells. Furthermore, PD
      0332991 treatment caused cell senescence in a FOXM1-dependent manner. In
      addition, there was synergy between PD-0332991 and cisplatin or 5-fluorouracil.
      Importantly, the xenografted tumour experiments demonstrated that PD-0332991
      potently inhibits ESCC cell growth and lung metastasis. CONCLUSIONS AND
      IMPLICATIONS: PD-0332991 can elicit a strong antitumour activity against ESCC
      growth and metastasis and may be a promising candidate drug for the treatment of
      patients with ESCC. Our results warrant a clinical trial to further evaluate the
      efficacy of PD-0332991 in ESCC patients, even those with metastasis.

PMID- 28444747
TI  - A randomized controlled trial of the ketogenic diet in refractory childhood
      epilepsy.

PMID- 28444748
TI  - Identification of coagulation gene 3'UTR variants that are potentially regulated
      by microRNAs.
AB  - MicroRNAs have been recognized as critical regulators of gene expression and
      might affect the risk of venous thrombosis. We aimed to identify 3' untranslated
      region (UTR) variants in coagulation genes that influence coagulation factor
      levels and venous thrombosis risk. The 3'UTR of coagulation genes were sequenced
      in subjects with extremely high or low plasma levels of these factors in two case
      control studies. In total, 28 variants were identified. Five single nucleotide
      polymorphisms (SNPs) were predominantly present in one extreme level group (F2
      rs1799963, F8 rs1050705 and F11 rs4253429, rs4253430 and rs1062547). Additional
      to F2 rs1799963, F8 rs1050705 (in men) and F11 rs4253430 were associated with an
      increased risk of venous thrombosis albeit confidence intervals were wide. The
      three F11 SNPs were in high linkage disequilibrium with functional variants
      rs2289252 and rs2036914. Rs1062547 and rs4253430 were associated with a
      significant increase of plasma FXI activity in heterozygotes and homozygotes in
      wild-type controls. In silico prediction revealed that these SNPs might disturb
      the binding sites of miR-544 and miR-513a-3p. Only miR-544 provoked a significant
      decrease of the luciferase activity that was not observed with a rs4253430
      mutated vector. In conclusion, these results reinforce that microRNAs are
      candidates to play a role in haemostasis and complex disorders, such as
      thrombosis.

PMID- 28444749
TI  - Transurethral removal of a cystic urolith in a mare using a laparoscopic specimen
      pouch.
AB  - CASE REPORT: Cystic urolithiasis is the most common form of urolithiasis reported
      in horses. In contrast to the gelding or stallion, clinical disease is less
      common in the mare and manual removal techniques are possible because of their
      shorter, wider urethral anatomy. However, these manual removal techniques can be
      traumatic and are limited by the size of the urolith. This report describes the
      use of a commercial laparoscopic specimen pouch to remove a cystic urolith in a
      mare. CONCLUSION: This approach may allow the extraction of larger uroliths per
      urethra in the mare, while affording some protection to the mucosa of the bladder
      neck and urethra.

PMID- 28444751
TI  - Valentins Sloss 1922-2016.

PMID- 28444752
TI  - Prevalence and pathogen load of Campylobacter spp., Salmonella enterica and
      Escherichia coli O157/O145 serogroup in sheep faeces collected at sale yards and
      in abattoir effluent in Western Australia.
AB  - OBJECTIVE: Develop a multiplex quantitative PCR assay to investigate the
      prevalence and shedding of Escherichia coli O157/O145, Salmonella spp. and
      Campylobacter spp. in sheep at sale yards and abattoirs. METHODS: A qPCR for E.
      coli O157/O145 was developed, validated and multiplexed with an existing qPCR for
      Campylobacter and Salmonella enterica. The absolute numbers of E. coli O157/O145,
      Campylobacter and Salmonella in control samples was determined using droplet
      digital PCR. These were then used as the controls in the multiplex qPCR on a
      total of 474 sheep faecal samples collected from two saleyards over a 4-month
      period (April-July 2014) and 96 effluent samples from an abattoir. RESULTS: The
      mutiplex qPCR was specific with a sensitivity of 5 organisms/MUL faecal DNA
      extract for Campylobacter, S. enterica and E. coli O157/O145. The overall
      prevalence of Campylobacter, S. enterica and E. coli O157/O145 in faecal samples
      was 5.7%, 3.6% and 8.4% and in effluent samples was 18.8%, 6.3% and 5.2%,
      respectively. The pathogen loads of Campylobacter, S. enterica and E. coli
      O157/O145 in faecal and effluent samples was also determined via mutiplex qPCR.
      CONCLUSIONS: The overall prevalences of Campylobacter, S. enterica and E. coli
      O157/O145 were generally low (<6%), but point prevalences ranged considerably in
      healthy sheep (up to 26% for E. coli O157/O145). Further work to determine risk
      factors for shedding of bacterial organisms in meat sheep in the pre-slaughter
      period (on-farm, sale yards and lairage at abattoirs) could further reduce the
      risk of contamination of meat products.

PMID- 28444753
TI  - Examination of toxicity and collagen linearity after the administration of the
      protein cross-linker genipin in equine tendon and dermis: a pilot study.
AB  - OBJECTIVE: Collagen cross-linking is an attractive therapeutic route aimed at
      supplementing natural collagen stabilisation. In this study the toxicity of the
      cross-linker genipin (GP) was examined in avascular (tendon) and vascular
      (dermis) tissue. METHODS: High doses of GP were injected intratendinously into
      three yearling horses and evaluated at various time points up to 30 days. A
      second group of three yearlings were injected into the dermis and evaluated at
      various time points up to 1 year. Metrics used included lameness, circumferential
      swelling, ultrasound evaluation, microscopic morphology, collagen production and
      systemic effect on blood parameters. RESULTS: The tendon injection sites
      exhibited mild lameness and swelling with no apparent systemic toxicity or
      stabilisation defects. Treated tendons exhibited increased linear collagen
      microscopically. Dermal injections showed similar results, with mild swelling at
      the injection site. Microscopic morphology resulted in a decrease in dermal
      collagen at 30 days post-injection. Dermis injected at the high dose of 355
      mmol/L examined 1 year post-treatment appeared similar to the untreated biopsies;
      however, there was an increase in mature collagen. CONCLUSION: GP injection
      appeared to be well tolerated, with transient lameness and mild circumferential
      swelling when injected into the tendon and local tissue swelling when injected
      into the dermis. No systemic hypersensitivities or toxicities were observed.
      Microscopically, GP resulted in increased linear collagen in tendons at 30 days
      post-injection and overall increased collagen in dermal tissue when evaluated 1
      year post-injection.

PMID- 28444754
TI  - Retrospective study on the occurrence of canine lymphoma and associated breed
      risks in a population of dogs in NSW (2001-2009).
AB  - OBJECTIVE: To identify risk factors for canine lymphoma in dogs from New South
      Wales, Australia, and to compare factors affecting remission duration. METHODS:
      Client-owned dogs diagnosed with lymphoma presented to the University Veterinary
      Teaching Hospital (UVTH), University of Sydney, between 2001 and 2009 (n = 134)
      were compared with a control population of dogs seen in that period of time with
      a diagnosis other than lymphoma to evaluate association of explanatory variables
      (breed, age and sex) with the outcome (case or control status). RESULTS: The
      Australian Cattle Dog (odds ratio (OR) = 4.71; 95% confidence interval (Cl) 2.31
      9.62; P < 0.001), Doberman (OR = 7.64; 95% Cl 2.87-20.34; P = 0.001) and
      Rottweiler (OR = 4.52; 95% Cl 2.09-9.73; P = 0.001) had increased odds of
      lymphoma among dogs attending the UVTH compared with crossbreds. The results
      suggested that the Border Collie (OR = 3.38; 95% Cl 1.52-7.53; P = 0.008) and
      Boxer (OR = 3.85; 95% Cl 1.65-8.95; P = 0.006) also have increased odds of
      lymphoma among the pure-breed dogs attending the UVTH when compared with
      crossbred dogs. CONCLUSIONS: The results of this study confirmed a breed
      predilection for lymphoma in dogs, with the Australian Cattle Dog and Doberman
      having increased odds of lymphoma.

PMID- 28444756
TI  - E7 (1057DeltaTA) mutation of the acidic alpha-glucosidase gene causes Pompe's
      disease in Droughtmaster cattle.
AB  - OBJECTIVE: To determine whether known loss-of-function alleles of the acidic
      alpha-glucosidase gene (GAA) are present in the Droughtmaster breed and, if so,
      whether the clinical signs and pathology of generalised glycogenosis (Pompe's
      disease) previously reported in other affected cattle are also seen in homozygous
      Droughtmasters. DESIGN: Existing genomic and other diagnostic tests developed for
      generalised glycogenosis in cattle were used to test for the presence of the
      three known loss-of-function alleles of GAA in a herd of Droughtmaster cattle.
      Two calves with clinical signs of generalised glycogenosis were submitted for
      necropsy. RESULTS: One loss-of-function GAA mutation (1057DeltaTA or E7 allele)
      was identified using SNP chip technology and confirmed using conventional
      diagnostic DNA tests. Further testing demonstrated that the mutation was common
      within this herd and that two ill-thrift calves were homozygous for the E7
      allele. Parentage analysis confirmed both sire and dam as heterozygous carriers.
      Pathology consistent with generalised glycogenosis was found in the skeletal and
      cardiac muscle and spinal cord of both of the affected calves. The 1783C>T (E13)
      or 2454DeltaCA (E18) mutations associated with generalised glycogenosis in the
      Brahman and Shorthorn breeds, respectively, were not detected. CONCLUSION: The
      lethal mutation 1057DeltaTA of GAA is present in the Droughtmaster breed, with
      pathology identical to that reported in pure Brahman animals. Droughtmaster
      breeders should take action to prevent any increase in the prevalence of this
      lethal allele in the breed as it could cause both welfare issues and production
      losses if ignored.

PMID- 28444757
TI  - Hypocobalaminaemia as a cause of bone marrow failure and pancytopenia in a cat.
AB  - CASE REPORT: A male Domestic Short-hair cat was presented for chronic weight
      loss, lethargy and hyporexia. Complete haematological examination revealed non
      regenerative anaemia, neutropenia and thrombocytopenia, as well as Howell-Jolly
      bodies, anisocytosis, polychromasia and macrocytosis on blood smear evaluation.
      Histopathological evaluation of bone marrow biopsy disclosed hypocellularity
      consistent with bone marrow failure. Concurrent hypocobalaminaemia was identified
      and treated with parenteral cyanocobalamin supplementation. Other differential
      diagnoses for pancytopenia, including infectious, toxic, immune-mediated and
      neoplastic causes, were ruled out. CONCLUSION: The cat's erythrocyte, leucocyte
      and platelet counts normalised after 2 months of cyanocobalamin supplementation,
      suggesting that pancytopenia may be a rare manifestation of feline cobalamin
      deficiency.

PMID- 28444758
TI  - Intraoperative use of a transarticular circular fixator construct to facilitate
      reduction and stabilisation of a proximal tibial physeal fracture in a dog.
AB  - CASE REPORT: A 4-month-old female intact American Pit Bull Terrier was presented
      for right pelvic limb lameness 1 day after the dog had been hit by an all-terrain
      vehicle. Orthogonal radiographs of the right stifle revealed a Salter-Harris type
      IV fracture through the proximal tibial physis extending caudodistally through
      the proximal tibial metaphysis. The distal tibia was markedly displaced
      cranially, laterally and proximally, resulting in complete overriding of the
      fracture segments. An open approach was made in order to facilitate direct
      reduction, but the fracture could not be sufficiently distracted and the
      epiphyseal segment remained fixed caudal to the remainder of the tibia. Concerns
      regarding possible iatrogenic trauma to the epiphysis prompted the use of a
      transarticular circular fixator construct to distract the fracture segments to
      facilitate reduction. Distraction that facilitated reduction was performed using
      three TrueLok Rapid Quick Adjust Struts that were positioned between the two ring
      components. The struts also allowed for multiplanar adjustment of alignment,
      which allowed the fracture to be maintained in anatomic reduction as divergent
      interfragmentary Kirschner wires were placed. Radiographic union was confirmed 19
      days after surgery. CONCLUSION/CLINICAL SIGNIFICANCE: Transient intraoperative
      application of a circular construct incorporating the TrueLok components
      facilitated accurate fracture reduction without inflicting further iatrogenic
      trauma to the epiphysis, after traditional direct reduction techniques proved
      ineffective, and afforded a successful clinical outcome in the dog reported here.

PMID- 28444759
TI  - Dysregulated CD46 shedding interferes with Th1-contraction in systemic lupus
      erythematosus.
AB  - IFN-gamma-producing T helper 1 (Th1) cell responses mediate protection against
      infections but uncontrolled Th1 activity also contributes to a broad range of
      autoimmune diseases. Autocrine complement activation has recently emerged as key
      in the induction and contraction of human Th1 immunity: activation of the
      complement regulator CD46 and the C3aR expressed by CD4+ T cells via autocrine
      generated ligands C3b and C3a, respectively, are critical to IFN-gamma
      production. Further, CD46-mediated signals also induce co-expression of
      immunosuppressive IL-10 in Th1 cells and transition into a (self)-regulating and
      contracting phase. In consequence, C3 or CD46-deficient patients suffer from
      recurrent infections while dysregulation of CD46 signaling contributes to Th1
      hyperactivity in rheumatoid arthritis and multiple sclerosis. Here, we report a
      defect in CD46-regulated Th1 contraction in patients with systemic lupus
      erythematosus (SLE). We observed that MMP-9-mediated increased shedding of
      soluble CD46 by Th1 cells was associated with this defect and that inhibition of
      MMP-9 activity normalized release of soluble CD46 and restored Th1 contraction in
      patients' T cells. These data may deliver the first mechanistic explanation for
      the increased serum CD46 levels observed in SLE patients and indicate that
      targeting CD46-cleaving proteases could be a novel avenue to modulate Th1
      responses.

PMID- 28444760
TI  - Vancomycin levels are frequently subtherapeutic in critically ill patients: a
      prospective observational study.
AB  - BACKGROUND: Appropriate utilization of vancomycin is important to attain
      therapeutic targets while avoiding clinical failure and the development of
      antimicrobial resistance. Our aim was to observe the use of vancomycin in an
      intensive care population, with the main focus on achievement of therapeutic
      serum concentrations (15-20 mg/l) and to evaluate how this was influenced by dose
      regimens, use of guidelines and therapeutic drug monitoring. METHODS: A
      prospective observational study was carried out in the intensive care units at
      two tertiary hospitals in Norway. Data were collected from 83 patients who
      received vancomycin therapy, half of these received continuous renal replacement
      therapy. Patients were followed for 72 h after initiation of therapy. Blood
      samples were drawn for analysis of trough serum concentrations. Urine was
      collected for calculations of creatinine clearance. Information was gathered from
      medical records and electronic health records. RESULTS: Less than 40% of the
      patients attained therapeutic trough serum concentrations during the first 3 days
      of therapy. Patients with augmented renal clearance had lower serum trough
      concentrations despite receiving higher maintenance doses and more loading doses.
      When trough serum concentrations were outside of therapeutic range, dose
      adjustments in accordance to therapeutic drug monitoring were made to less than
      half. CONCLUSION: The present study reveals significant challenges in the
      utilization of vancomycin in critically ill patients. There is a need for clearer
      guidelines regarding dosing and therapeutic drug monitoring of vancomycin for
      patient subgroups.

PMID- 28444761
TI  - Photon-counting CT for simultaneous imaging of multiple contrast agents in the
      abdomen: An in vivo study.
AB  - PURPOSE: To demonstrate the feasibility of spectral imaging using photon-counting
      detector (PCD) x-ray computed tomography (CT) for simultaneous material
      decomposition of three contrast agents in vivo in a large animal model. METHODS:
      This Institutional Animal Care and Use Committee-approved study used a canine
      model. Bismuth subsalicylate was administered orally 24-72 h before imaging. PCD
      CT was performed during intravenous administration of 40-60 ml gadoterate
      meglumine; 3.5 min later, iopamidol 370 was injected intravenously. Renal PCD CT
      images were acquired every 2 s for 5-6 min to capture the wash-in and wash-out
      kinetics of the contrast agents. Least mean squares linear material decomposition
      was used to calculate the concentrations of contrast agents in the aorta, renal
      cortex, renal medulla and renal pelvis. RESULTS: Using reference vials with known
      concentrations of materials, we computed molar concentrations of the various
      contrast agents during each phase of CT scanning. Material concentration maps
      allowed simultaneous quantification of both arterial and delayed renal
      enhancement in a single CT acquisition. The accuracy of the material
      decomposition algorithm in a test phantom was -0.4 +/- 2.2 mM, 0.3 +/- 2.2 mM for
      iodine and gadolinium solutions, respectively. Peak contrast concentration of
      gadolinium and iodine in the aorta, renal cortex, and renal medulla were observed
      16, 24, and 60 s after the start each injection, respectively. CONCLUSION: Photon
      counting spectral CT allowed simultaneous material decomposition of multiple
      contrast agents in vivo. Besides defining contrast agent concentrations, tissue
      enhancement at multiple phases was observed in a single CT acquisition,
      potentially obviating the need for multiphase CT scans and thus reducing
      radiation dose.

PMID- 28444762
TI  - Screening allergic reactions to resol resin based on phenol and formaldehyde in a
      clinic of occupational dermatology.
AB  - BACKGROUND: Allergic reactions to resol-type phenol formaldehyde resin [phenol
      formaldehyde resin 2 (PFR2)] are relatively common. It has been suggested that
      PFR2 should be included in baseline series. However, a recent international study
      found clinical relevance in only 25% of patients. OBJECTIVES: To report the
      results of screening with PFR2 over a 5-year period (2012-2016), and to study the
      clinical relevance of allergic reactions to PFR2 over a 15-year period (2002
      2016). METHODS: At the Finnish Institute of Occupational Health, PFR2 was added
      to the baseline series in 2012. We had previously tested PFR2 in the plastic and
      glue series. We searched the patch test files for patients with allergic
      reactions to PFR2, and analysed their patch test results, occupation, exposure,
      and diagnosis. RESULTS: During the screening period of 5 years, a total of 10
      (1.6%) patients reacted positively to PFR2. Seven of these had occupational
      allergic contact dermatitis caused by phenol formaldehyde resin (PFR). In 3
      patients, we found no exposure to PFR. Over the preceding 10 years, the clinical
      relevance of 10 additional allergic reactions to PFR2 was similarly high.
      CONCLUSIONS: In an occupational dermatology clinic, 70% of PFR2 reactions were
      clinically relevant. Further studies in general dermatology clinics are needed.

PMID- 28444763
TI  - Manganese concentration mapping in the rat brain with MRI, PET, and
      autoradiography.
AB  - PURPOSE: Mn2+ is used as a contrast agent and marker for neuronal activity with
      magnetic resonance imaging (MRI) in rats and mice, but its accumulation is
      generally not assessed quantitatively. In this work, nonradioactive Mn and 52 Mn
      are injected simultaneously in rats, and imaged with MRI, positron emission
      tomography (PET) and autoradiography (AR). Mn distributions are compared between
      modalities, to assess the potential and limitations on quantification of Mn with
      MRI, and to investigate the potential of multimodal measurement of Mn
      accumulation. METHODS: MRI (in vivo), PET (in vivo and post mortem), and AR (ex
      vivo) were acquired of rat brains, for which animals received simultaneous
      intraperitoneal (IP) or intracerebrovertricular (ICV)-targeted injections
      containing the positron-emitting radionuclide 52 Mn and additional nonradioactive
      MnCl2 , which acts as an MRI contrast agent. Pre and postinjection MR images were
      fit for the longitudinal relaxation rate (R1), coregistered, and subtracted to
      generate R1 difference maps, which are expected to be proportional to change in
      Mn concentration in tissue. AR and PET images were coregistered to smoothed R1
      difference maps. RESULTS: Similar spatial distributions were seen across
      modalities, with Mn accumulation in the colliculus, near the injection site, and
      in the 4th ventricle. There was no 52 Mn accumulation measurable with PET in the
      brain after IP injection. In areas of very highly localized and concentrated 52
      Mn accumulation in PET or AR, consistent increases of R1 were not seen with MRI.
      Scatter plots of corresponding voxel R1 difference and PET or AR signal intensity
      were generated and fit with least squares linear models within anatomical
      regions. Linear correlations were observed, particularly in regions away from
      very highly localized and concentrated Mn accumulation at the injection site and
      the 4th ventricle. Accounting for radioactive decay of 52 Mn, the MnCl2
      longitudinal relaxivity was between 4.0 and 5.1 s-1 /mM, which is within 22% of
      the in vitro relaxivity. CONCLUSIONS: This proof-of-concept study demonstrates
      that MR has strong potential for quantitative assessment of Mn accumulation in
      the brain, although local discrepancies from linear correlation suggest
      limitations to this use of MR in areas of inflammation or very high
      concentrations of Mn. These discrepancies also suggest that a combination of
      modalities may have additional utility for discriminating between different pools
      of Mn accumulation in tissue.

PMID- 28444764
TI  - Prospective unbiased experience with three acellular dermal matrices in breast
      reconstruction.
AB  - BACKGROUND: The use of acellular dermal matrix (ADM) has become the standard of
      care in breast reconstruction. However, the majority of current studies are
      biased or combine large databases introducing inherent flaws. Here, we present a
      prospective single surgeon experience comparing three ADM. METHODS: All expander
      based breast reconstructions between 2014 and 2015 using ADM were included.
      RESULTS: Eighteen patients (32 breasts) underwent reconstruction using Flex
      Pliable, 15 patients (22 breasts) used Alloderm, and 14 patients (20 breasts) had
      Dermacell. There were no significant differences in patient demographics or
      comorbidities. All expanders were placed into a subpectoral position, and there
      were no direct to implant cases. Average intraoperative fill was comparable,
      (Flex: 225 cc, Alloderm: 180 cc, Dermacell: 130 cc). There were no differences in
      seroma, infection, or mastectomy skin flap necrosis rates. There were no cases of
      red breast, expander explanation or failed reconstruction in any cohort. Time to
      drain removal was significantly shorter in Flex and Dermacell patients compared
      to Alloderm (20 days vs 15 days vs 26 days, respectively; P = 0.01). CONCLUSIONS:
      While there are differences between available ADM, successful outcomes can be
      achieved with proper patient selection, sound surgical technique, and diligent
      post-operative management.

PMID- 28444765
TI  - Interinstrumental transfer of a fast short-end injection capillary
      electrophoresis method: Application to the separation of niobium, tantalum, and
      their substituted ions.
AB  - The interinstrumental transfer of a short-end CE method was studied. A model
      separation of the hexameric forms of niobium, tantalum, and their substituted
      ions (Nb6-x Tax with 0 <= x <= 6) was selected as test case. The method was first
      optimized on a Beckman instrument and in a second step transferred to an Agilent
      instrument. The transfer needed updated guidelines that tackled differences in
      effective capillary length, 8.5 (Agilent) versus 10 cm (Beckman), because of
      instrumental different capillary cartridges. Differences in effective length lead
      to migration time and separation efficiency inequalities, illustrated by a
      decrease in resolution between the substituted ions. The difference in effective
      length was overcome by adapting the lift offset parameter of the Agilent
      instrument. The lift offset default setting is 4 mm and by increasing this
      parameter both the inlet and outlet lifts are lowered and thus the detection
      window can be displaced and consequently the effective length was increased. The
      decrease in effective length difference and the effect on the separation
      efficiency was investigated and led finally to a restored separation of the
      substituted ions. The adaptation of the lift offset parameter during short-end
      injection methods was added to earlier developed guidelines to facilitate
      interinstrumental method transfer of CE methods.

PMID- 28444766
TI  - Endoplasmic reticulum stress mediates distinct impacts of sevoflurane on
      different subfields of immature hippocampus.
AB  - Sevoflurane, a typical inhaled anesthetic, is widely used in patients of all ages
      during surgery. The negative effects, such as inducing cell death and damaging
      spatial memory, of sevoflurane on neurodevelopment have raised increasing
      concerns in recent years. However, the molecular mechanism remains unclear. This
      study focused on the crucial role of endoplasmic reticulum (ER) stress in
      sevoflurane-induced hippocampal injury. Three-week-old rats were exposed to
      sevoflurane or control air for 5 h with or without ER stress inhibitor (4
      phenylbutyric acid, 4-PBA) injection. The hippocampus was harvested to measure
      the ER stress sensors by western immunoblotting. Terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end-labeling staining was used to detect cell
      apoptosis and electrophysiology was used to measure the intrinsic excitability of
      neurons in hippocampus. We measured learning and memory ability by Morris water
      maze tests 5 weeks after sevoflurane exposure. Interestingly, persistent
      sevoflurane exposure significantly increased the levels of ER stress sensors in
      hippocampus. But it resulted in different effects in CA1 and dentate gyrus.
      Greatly increased caspase-12-mediated apoptotic cells, which were proved to be
      the neural stem cells, were detected in the dentate gyrus. Meanwhile, CA1
      pyramidal neurons exhibited significantly reduced intrinsic excitability.
      Furthermore, the administration of ER stress inhibitor attenuated the above
      mentioned detrimental effects evidently and prevented the following relevant
      learning and memory deficits. In conclusion, sevoflurane-mediated ER stress
      performs distinct effects on the different subfields of the immature hippocampus
      and inhibiting ER stress during sevoflurane anesthesia will be a potential method
      to prevent the following learning and memory deficits in adulthood.

PMID- 28444767
TI  - The dual orexin receptor antagonist, DORA-22, lowers histamine levels in the
      lateral hypothalamus and prefrontal cortex without lowering hippocampal
      acetylcholine.
AB  - Chronic insomnia is defined as a persistent difficulty with sleep initiation
      maintenance or non-restorative sleep. The therapeutic standard of care for this
      condition is treatment with gamma-aminobutyric acid (GABA)A receptor modulators,
      which promote sleep but are associated with a panoply of side effects, including
      cognitive and memory impairment. Dual orexin receptor antagonists (DORAs) have
      recently emerged as an alternative therapeutic approach that acts via a distinct
      and more selective wake-attenuating mechanism with the potential to be associated
      with milder side effects. Given their distinct mechanism of action, the current
      work tested the hypothesis that DORAs and GABAA receptor modulators
      differentially regulate neurochemical pathways associated with differences in
      sleep architecture and cognitive performance induced by these pharmacological
      mechanisms. Our findings showed that DORA-22 suppresses the release of the wake
      neurotransmitter histamine in the lateral hypothalamus, prefrontal cortex, and
      hippocampus with no significant alterations in acetylcholine levels. In contrast,
      eszopiclone, commonly used as a GABAA modulator, inhibited acetylcholine
      secretion across brain regions with variable effects on histamine release
      depending on the extent of wakefulness induction. In normal waking rats,
      eszopiclone only transiently suppressed histamine secretion, whereas this
      suppression was more obvious under caffeine-induced wakefulness. Compared with
      the GABAA modulator eszopiclone, DORA-22 elicits a neurotransmitter profile
      consistent with wake reduction that does not impinge on neurotransmitter levels
      associated with cognition and rapid eye movement sleep.

PMID- 28444768
TI  - Implantable Doppler monitoring of buried free flaps during vascularized lymph
      node transfer.
AB  - BACKGROUND AND OBJECTIVES: Reliable flap monitoring is crucial to the success of
      free tissue transfer, including vascularized lymph node transfer (VLNT). However,
      no large-scale study has examined implantable Doppler monitoring in VLNT. We
      aimed to determine whether an implantable Doppler system can reliably monitor
      flap perfusion during VLNT and also to calculate the sensitivity and specificity
      of this system for detecting compromise in the monitored vessel. METHODS: An
      analysis of prospectively collected data of patients who underwent buried VLNT
      with implantable Doppler monitoring between 2014 and 2015 was performed. RESULTS:
      A consecutive series of 100 patients underwent VLNT with implantable Doppler
      monitoring. Five cases required return to the operating room for flap exploration
      due to a change in Doppler signal quality. All compromised flaps were salvaged.
      The sensitivity of the implantable Doppler system for flap monitoring was 100%,
      the specificity was 97.9%, the positive predictive value was 60%, and the
      negative predictive value was 100%. The false-positive rate was 2%. CONCLUSIONS:
      This is the largest reported series of implantable Doppler monitoring of free
      flap perfusion during VLNT. Our experience suggests that this is a safe and
      effective technique for postoperative monitoring of VLNT.

PMID- 28444769
TI  - Lesion of the basal forebrain cholinergic neurons attenuates sleepiness and
      adenosine after alcohol consumption.
AB  - Alcohol has a profound effect on sleep. However, neuronal substrates mediating
      sleep-promoting effects of alcohol are unknown. Since the basal forebrain (BF)
      cholinergic neurons are implicated in the homeostatic regulation of sleep, we
      hypothesized that the BF cholinergic neurons may have an important role in
      sleepiness observed after alcohol consumption. 192-IgG-saporin (bilateral BF
      infusions) was used to selectively lesion BF cholinergic neurons in adult male
      Sprague-Dawley rats. Standard surgical procedures were used to implant sleep
      recording electrodes or microdialysis guide cannulas. The first experiment used
      between-group design [lesion and sham (controls)] and examined effects of BF
      cholinergic neuronal lesions on alcohol (3 g/Kg; ig) induced sleep promotion. The
      second experiment used within-group design [lesion (ipsilateral BF) and sham
      (controls; contralateral BF) in same animal] and local reverse microdialysis
      infusion of alcohol (300 mM) to examine the effects of cholinergic neuronal
      lesions on extracellular adenosine in the BF. Alcohol had a robust sleep
      promoting effect in controls as evidenced by a significant reduction in sleep
      onset latency and wakefulness; non-rapid eye movement sleep was significantly
      increased. No such alcohol-induced sleep promotion was observed in lesioned rats
      with significantly fewer BF cholinergic neurons. Rapid eye movement sleep was
      minimally affected. Adenosine release was significantly reduced following local
      infusion of alcohol on the lesion side, with significantly fewer cholinergic
      neurons as compared with the control side. Based on these results, we suggest
      that alcohol promotes sleep by increasing extracellular adenosine via its action
      on cholinergic neurons of the BF. Read the Editorial Highlight for this article
      on page 620.

PMID- 28444770
TI  - Factors associated with local recurrence in operated osteosarcomas: A
      retrospective evaluation of 95 cases from a tertiary care center in a resource
      challenged environment.
AB  - BACKGROUND AND OBJECTIVES: Local control of disease is one of the main goals of
      osteosarcoma management. We conducted a retrospective evaluation of 95 operated
      cases of osteosarcoma over 7 years to know about the factors associated with
      local recurrence in resource-challenged environment of the developing world.
      METHODS: The factors which were evaluated and compared between local recurrence
      and non-local recurrence groups included demographic profile, site of tumor,
      whether biopsy done outside, type of surgery (limb salvage or amputation),
      presence of pathological fracture, vicinity of neurovascular bundle, tumor
      volume, histological subtype, chemotherapy induced necrosis, surgical margins,
      and delay in surgery. The time to local recurrence after surgery was also noted
      in the local recurrence group. RESULTS: At a mean follow-up of 2.8 years, biopsy
      done from outside the treating center and delay in surgery after completion of
      neo-adjuvant chemotherapy emerged as significant risk factors for local
      recurrence. Most of the local recurrences (80%) occurred within 12 months of the
      primary surgery. CONCLUSIONS: Lack of financial resources and availability of few
      tertiary care centers dealing with musculoskeletal oncology in the developing
      countries, lead to overburden with a long waiting list for tumor surgery making
      the scenario different from the Western world.

PMID- 28444771
TI  - Oestrone-targeted liposomes for mitoxantrone delivery via oestrogen receptor -
      synthesis, physicochemical characterization and in-vitro evaluation.
AB  - OBJECTIVES: Targeted delivery of mitoxantrone (MTO, an anthraquinone drug with
      high antitumour effect) may be achieved using a novel nanoparticulate delivery
      system via binding the oestrogen receptor (ER, highly expressed in a variety of
      human tumours). METHODS: A novel liposomal nanoparticle (NP) was developed using
      a conjugate derived from 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N
      [amino (polyethylene glycol)-2000] (DSPE-PEG2000 -NH2 ) and oestrone (ES, is
      known to bind the ER) to produce an ES-targeted PEGylated liposome (ES-SSL). The
      resulting targeted NP was loaded with MTO to produce a targeted liposome-MTO
      formulation (ES-SSL-MTO). KEY FINDINGS: The targeted formulation (~140 nm, 1.5
      mV) achieved over 95% drug encapsulation efficiency and a favourable stability at
      4, 25 and 37  degrees C up to 48 h. The flow cytometric data indicated that
      cellular uptake of ES-SSL into human leukaemia HL-60 cells was mediated via
      binding the oestrogen receptor. In addition, the ES-SSL-MTO significantly reduced
      the growth of HL-60 cells. CONCLUSIONS: Our results provide a proof of principle
      that ES-modified PEGylated liposomes can target the ER, thereby potentially
      improving the therapeutic benefits in ER-overexpressed tumours.

PMID- 28444772
TI  - Multiatlas approach with local registration goodness weighting for MRI-based
      electron density mapping of head and neck anatomy.
AB  - PURPOSE: The growing use of magnetic resonance imaging (MRI) as a substitute for
      computed tomography-based treatment planning requires the development of
      effective algorithms to generate electron density maps for treatment planning and
      patient setup verification. The purpose of this work was to develop a method to
      synthesize computerized tomography (CT) for MR-only radiotherapy of head and neck
      cancer patients. METHODS: The algorithm is based on registration of multiple
      patient datasets containing both MRI and CT images (a "multiatlas" algorithm).
      Twelve matched pairs of good quality CT and MRI scans (those without apparent
      motion and blurring artifacts) were selected from a pool of head and neck cancer
      patients to form the atlas. All atlas MRI scans were preprocessed to reduce
      scanner- and patient-induced intensity inhomogeneities and to standardize their
      intensity histograms. Atlas CT and MRIs were coregistered using a novel bone-to
      air replacement technique applied to the CT scans that improves the similarity
      between CTs and MRIs and facilitates the registration process. For each new
      patient, all atlas MRIs are deformed initially onto the new patients' MRI. We
      introduce a generalized registration error (GRE) metric that automatically
      measures the goodness of local registration between MRI pairs. The final
      synthetic CT value at each point is a nonlinear GRE-weighted average of the atlas
      CTs. For evaluation, the leave-one-out technique was used for synthetic CT
      generation and the mean absolute error (MAE) between the original and synthetic
      CT was computed over the entire CT image. The impact of our proposed CT-MR
      registration scheme on the accuracy of the final synthetic CT was also studied.
      The original treatment plans were also recomputed on the new synthetic CTs and
      dose-volume histogram metrics were compared. In addition, the two-dimensional
      (2D) gamma analysis at 1%/1 mm and 2%/2 mm dose difference/distance to agreement
      was also performed to study the dose distribution at the isocenter. RESULTS: MAE
      error (+/- standard deviation) between the original and the synthetic CTs was 64
      +/- 10, 113 +/- 12, and 130 +/- 28 Hounsfield Unit (HU) for the entire image,
      air, and bone regions respectively. Our results showed that our proposed bone
      suppression based CT-MR fusion and GRE-weighted strategy could lower the overall
      MAE error between the original and synthetic CTs by ~69% and ~34% respectively.
      Dose recalculation comparison showed highly consistent results between plans
      based on the synthetic vs. the original CTs. The 2D gamma analysis revealed the
      pass rate of 95.44 +/- 2.5 and 99.36 +/- 0.71 for 1%/1 mm and 2%/2 mm criteria
      respectively. Due to local registration weighting, the method is robust with
      respect to MRI imaging artifacts. CONCLUSION: We developed a novel image analysis
      technique to synthesize CT for head and neck anatomy. Novel methods were
      introduced to accurately register atlas CTs and MRIs as well as to weight the
      final electron density maps using local registration goodness estimates. The
      resulting accuracy is clinically acceptable, at least for these atlas patients.

PMID- 28444773
TI  - Mechanical dispersion and global longitudinal strain by speckle tracking
      echocardiography: Predictors of appropriate implantable cardioverter
      defibrillator therapy in hypertrophic cardiomyopathy.
AB  - PURPOSE: In this study, we investigated whether mechanical dispersion which
      reflects electrical abnormality and other echocardiographic and clinic parameters
      predict appropriate ICD shock in patients undergone ICD implantation for
      hypertrophic cardiomyopathy. METHODS: Sixty-three patients who received ICD
      implantation for primary or secondary prevention were included in the study.
      Patients' clinical, electrocardiographic, 2D classic, and speckle tracking
      echocardiographic data were collected. Mechanical dispersion was defined as the
      standard deviation of time to peak negative strain in 18 left ventricular
      segments. Appropriate ICD therapy was defined as cardioversion or defibrillation
      due to ventricular tachycardia or fibrillation. Patients were divided into two
      groups as occurrence or the absence of appropriate ICD therapy. RESULTS: A total
      of 17 (26.9%) patients were observed to have an appropriate ICD therapy during
      follow-up periods. In patients who performed appropriate ICD therapy, a larger
      left atrial volume index, higher sudden cardiac death (SCD)-Risk Score, longer
      mechanical dispersion, and decreased global longitudinal peak strain (GLPS) were
      observed. In multivariate logistic regression analysis, including (GLPS,
      mechanical dispersion, LAVi, and SCD-Risk Score) was used to determine
      independent predictors of occurrence of appropriate ICD therapy during the follow
      up. Mechanical dispersion, GLPS, and SCD-Risk Score were found to be independent
      predictors of occurrence of appropriate ICD therapy. CONCLUSIONS: Mechanical
      dispersion, GLPS, and SCD-Risk Score were found to be predictive for appropriate
      ICD therapy in patients receiving ICD implantation. Readily measurable mechanical
      dispersion and GLPS could be helpful to distinguish patients at high risk who
      could optimally benefit from ICD therapy.

PMID- 28444774
TI  - Protective effect of L-carnitine and L-arginine against busulfan-induced
      oligospermia in adult rat.
AB  - : Busulfan is an anticancer drug caused variety of adverse effects for patients
      with cancer. But it could cause damage to the male reproductive system as one of
      its adverse effects. This study aimed to investigate the protective effect of L
      carnitine and L-arginine on semen quality, oxidative stress parameters and testes
      cell energy after busulfan treatment. Adult male rats were divided into four
      groups: control (Con), busulfan (Bus), busulfan plus L-arginine (Bus + L-arg) and
      busulfan plus L-carnitine (Bus + L-car). After 28 days, the semen was collected
      from the epididymis and the testes were assessed. Sperm count, motility and
      velocity were measured by CASA, and smears were prepared for assessment of sperm
      morphology. Serum and testes supernatants were separated for DNA metabolites,
      oxidative stress and cell energy parameters. Testes tissues also subjected for
      caspase-3. The results showed significant improvement in sperm morphology,
      motility, velocity and count in the groups treated with L-arginine and L
      carnitine and accompanied with an increase in MDA, GSSG and ATP, reduction in
      GSH, AMP, ADP, NO and 8-OHDG also recorded. These results are supported by
      caspase-3. CONCLUSIONS: Administration of L-arg and L-car attenuated the
      cytotoxic effects of busulfan by improving semen parameters, reducing oxidative
      stress and maintaining cell energy.

PMID- 28444775
TI  - No rubbing, no elastosis perforans serpiginosa.

PMID- 28444776
TI  - In vitro effects of ambroxol on Cryptococcus adherence, planktonic cells, and
      biofilms.
AB  - The antifungal effects of ambroxol (Amb; the metabolite VIII of bromhexine)
      against Cryptococcus planktonic cells and mature biofilms were investigated in
      this study. Amb showed antifungal activity against planktonic cells and mature
      biofilms. Disk diffusion test similarly showed antifungal profile for planktonic
      cells. Furthermore, Amb was found to be synergetic with fluconazole against
      planktonic cells and reduced the adherence of cells to polystyrene. Our results
      suggest that Amb can inhibit cryptococcal cells and biofilms, indicating its
      potential role in the prevention and treatment of cryptococcosis.

PMID- 28444778
TI  - Development and implementation of an 84-channel matrix gradient coil.
AB  - PURPOSE: Design, implement, integrate, and characterize a customized coil system
      that allows for generating spatial encoding magnetic fields (SEMs) in a highly
      flexible fashion. METHODS: A gradient coil with a high number of individual
      elements was designed. Dimensions of the coil were chosen to mimic a whole-body
      gradient system, scaled down to a head insert. Mechanical shape and wire layout
      of each element were optimized to increase the local gradient strength while
      minimizing eddy current effects and simultaneously considering manufacturing
      constraints. RESULTS: Resulting wire layout and mechanical design is presented. A
      prototype matrix gradient coil with 12 * 7 = 84 elements consisting of two
      element types was realized and characterized. Measured eddy currents are <1% of
      the original field. The coil is shown to be capable of creating nonlinear, and
      linear SEMs. In a DSV of 0.22 m gradient strengths between 24 mT/m and 78 mT/m
      could be realized locally with maximum currents of 150 A. Initial proof-of
      concept imaging experiments using linear and nonlinear encoding fields are
      demonstrated. CONCLUSION: A shielded matrix gradient coil setup capable of
      generating encoding fields in a highly-flexible manner was designed and
      implemented. The presented setup is expected to serve as a basis for validating
      novel imaging techniques that rely on nonlinear spatial encoding fields. Magn
      Reson Med 79:1181-1191, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 28444777
TI  - Interphase FISH for BCR-ABL1 rearrangement on neutrophils: A decisive tool to
      discriminate a lymphoid blast crisis of chronic myeloid leukemia from a de novo
      BCR-ABL1 positive acute lymphoblastic leukemia.
AB  - Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML)
      and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a
      diagnostic challenge because this distinction has a major incidence on the
      management of patients. Here, we report an uncommon pediatric case of ALL with
      cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed
      interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement
      on blood neutrophils, which was positive consistent with the diagnosis of
      lymphoid blast crisis of CML. This case illustrates the major interest of
      interphase FISH for BCR-ABL1 rearrangement on blood neutrophils as a decisive
      method to discriminate a lymphoid blast crisis of CML from a de novo BCR-ABL1
      positive ALL.

PMID- 28444779
TI  - A randomised controlled trial of propofol vs. thiopentone and desflurane for
      fatigue after laparoscopic cholecystectomy.
AB  - Fatigue may delay functional recovery after day surgery and may be more common
      after propofol anaesthesia. We randomly allocated 123 participants scheduled for
      ambulatory laparoscopic cholecystectomy to induction and maintenance of general
      anaesthesia with propofol or thiopentone and desflurane. Postoperative fatigue
      was unaffected by the allocated anaesthetic. The combined mean (SD) Identity
      Consequences Fatigue Scale of 34.3 (15.1) before surgery increased in the first
      postoperative week: to 60.4 (21.1) on day 1, p < 0.001; to 51.1 (17.2) on day 2,
      p < 0.001; and to 37.5 (16.3) on day 6, p = 0.028. The mean (SD) fatigue reduced
      at one postoperative month to 22.4 (12.6), 35% less than the combined pre
      operative level, p < 0.001. Rates of nausea, vomiting and rescue antie-mesis
      during the first week after propofol, compared with thiopentone and desflurane,
      were: 23/63 vs. 32/60, p = 0.27; 8/63 vs. 9/60, p = 0.71; and 12/63 vs. 28/60, p
      = 0.001, respectively. There were no differences in postoperative pain. In
      conclusion, fatigue after scheduled laparoscopic cholecystectomy was unaffected
      by anaesthesia with propofol vs. thiopentone and desflurane.

PMID- 28444780
TI  - Fetal brain injury in complicated monochorionic pregnancies: diagnostic yield of
      prenatal MRI following surveillance ultrasound and influence on prognostic
      counselling.
AB  - OBJECTIVE: This study aimed to determine the additional diagnostic information
      provided by prenatal (fetal) magnetic resonance imaging (pMRI) following tertiary
      ultrasound (US) for fetal cranial abnormalities in complicated monochorionic
      gestations. METHODS: Women with complicated monochorionic gestations complicated
      by twin-twin transfusion syndrome, co-twin demise (CD), selective intrauterine
      growth restriction, and/or twin anaemia-polycythaemia sequence who were referred
      for pMRI after tertiary US were included. Additional diagnostic information by
      pMRI that changed prognostic counselling was the primary outcome. RESULTS: Thirty
      three women with 48 live fetuses had pMRI at a median of 25 weeks (range: 21-29).
      Three of ten survivors of spontaneous CD, one of eight survivors of CD after twin
      twin transfusion syndrome and 1/30 co-survivors had diagnostic information added
      by pMRI that altered counselling; US was normal in two and in the other three
      underrepresented parenchymal injury (5/33 = 15%; 95% confidence interval +/-0.27
      0.03). Additional findings included occipital lobe infarction, hemispheric
      injury, dural sinus thrombosis, ischaemia-producing polymicrogyria and
      intraventricular haemorrhage. Another 8/33 women had additional information
      provided by pMRI that did not alter counselling. CONCLUSION: Prenatal magnetic
      resonance imaging resulted in changed prognostic counselling in 5/33 pregnancies.
      Evaluation of incorporation of pMRI into routine surveillance of complicated
      monochorionic gestations is needed. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444781
TI  - Constructing longitudinal disease progression curves using sparse, short-term
      individual data with an application to Alzheimer's disease.
AB  - In epidemiology, cohort studies utilised to monitor and assess disease status and
      progression often result in short-term and sparse follow-up data. Thus, gaining
      an understanding of the full-term disease pathogenesis can be difficult,
      requiring shorter-term data from many individuals to be collated. We investigate
      and evaluate methods to construct and quantify the underlying long-term
      longitudinal trajectories for disease markers using short-term follow-up data,
      specifically applied to Alzheimer's disease. We generate individuals' follow-up
      data to investigate approaches to this problem adopting a four-step modelling
      approach that (i) determines individual slopes and anchor points for their short
      term trajectory, (ii) fits polynomials to these slopes and anchor points, (iii)
      integrates the reciprocated polynomials and (iv) inverts the resulting curve
      providing an estimate of the underlying longitudinal trajectory. To alleviate the
      potential problem of roots of polynomials falling into the region over which we
      integrate, we propose the use of non-negative polynomials in Step 2. We
      demonstrate that our approach can construct underlying sigmoidal trajectories
      from individuals' sparse, short-term follow-up data. Furthermore, to determine an
      optimal methodology, we consider variations to our modelling approach including
      contrasting linear mixed effects regression to linear regression in Step 1 and
      investigating different orders of polynomials in Step 2. Cubic order polynomials
      provided more accurate results, and there were negligible differences between
      regression methodologies. We use bootstrap confidence intervals to quantify the
      variability in our estimates of the underlying longitudinal trajectory and apply
      these methods to data from the Alzheimer's Disease Neuroimaging Initiative to
      demonstrate their practical use. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444782
TI  - Delayed-onset heat intolerance in a Japanese patient with X-linked hypohidrotic
      ectodermal dysplasia associated with a large deletion involving four genes.

PMID- 28444783
TI  - Taiwanese and Sri Lankan students' dimensions and discourses of professionalism.
AB  - CONTEXT: The definition of medical professionalism poses a challenge to global
      medical educators. This is especially pronounced in settings where
      professionalism frameworks developed in the west are transferred into different
      cultures. Building upon our previous study across Western contexts, we examine
      Taiwanese and Sri Lankan medical students' conceptualisations of professionalism
      in terms of what professionalism comprises (i.e. dimensions) and how it is
      linguistically framed (i.e. discourses). METHODS: A qualitative group interview
      study was undertaken comprising 26 group interviews with 135 participants from
      one Taiwanese (n = 64; Years 4-7) and one Sri Lankan medical school (n = 71;
      Years 2-5). Through thematic framework analysis we examined the data for explicit
      dimensions of professionalism. Through discourse analysis we identified how
      participants constructed professionalism linguistically (discourses). RESULTS:
      Thirteen common dimensions across Taiwanese and Sri Lankan talk were identified,
      with the dimensions (contextual, integration and internalised self) being
      identified only in Sri Lankan data. Professionalism as knowledge and patient
      centredness were dominant dimensions in Taiwan; in Sri Lanka, attributes of the
      individual and rules were dominant dimensions. Participants in both countries
      used four types of discourses previously identified in the literature. Individual
      and interpersonal discourses were dominant in Taiwanese talk; the collective
      discourse was dominant in Sri Lankan talk. Findings were compared with our
      previous data collected in Western contexts. CONCLUSIONS: Despite some overlap in
      the dimensions and discourses identified across both this and Western studies,
      Taiwanese and Sri Lankan students' dominant dimensions and discourses were
      distinct. We therefore encourage global medical educators to look beyond a one
      size-fits-all approach to professionalism, and to recognise the significance of
      context and culture in conceptualisations of professionalism.

PMID- 28444785
TI  - Liquid-Crystalline Elastomers with Gold Nanoparticle Cross-Linkers.
AB  - Embedding nanoparticles in a responsive polymer matrix is a formidable way to
      fabricate hybrid materials with predesigned properties and prospective
      applications in actuators, mechanically tunable optical elements, and
      electroclinic films. However, achieving chemical compatibility between
      nanoparticles and organic matter is not trivial and often results in disordered
      structures. Herein, it is shown that using nanoparticles as exclusive cross
      linkers in the preparation of liquid-crystalline polymers can yield long-range
      ordered liquid-crystalline elastomers with high loadings of well-dispersed
      nanoparticles, as confirmed by small-angle XRD measurements. Moreover, the
      strategy of incorporating NPs as cross-linking units does not result in
      disruption of mechanical properties of the polymer, and this phenomenon was
      explained by the means of all-atom molecular dynamics simulations. Such materials
      can exhibit switchable behavior under thermal stimulus with stability spanning
      over multiple heating/cooling cycles. The presented strategy has proven to be a
      promising approach for the preparation of new types of hybrid liquid-crystalline
      elastomers that can be of value for future photonic applications.

PMID- 28444784
TI  - Earlier defibrotide initiation post-diagnosis of veno-occlusive
      disease/sinusoidal obstruction syndrome improves Day +100 survival following
      haematopoietic stem cell transplantation.
AB  - Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a
      progressive, potentially fatal complication of conditioning for haematopoietic
      stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves
      endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic
      state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be
      associated with >80% mortality. Defibrotide is approved for treating severe
      hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with
      renal or pulmonary dysfunction post-HSCT in the United States. Previously,
      defibrotide (25 mg/kg/day in 4 divided doses for a recommended >=21 days) was
      available through an expanded-access treatment protocol for patients with
      VOD/SOS. Data from this study were examined post-hoc to determine if the timing
      of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post
      HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis
      in approximately 30%, and within 7 days in >90%. The relationship between Day
      +100 survival and treatment initiation before/after specific days post-diagnosis
      showed superior survival when treatment was initiated closer to VOD/SOS diagnosis
      with a statistically significant trend over time for better outcomes with earlier
      treatment initiation (P < 0.001). These results suggest that initiation of
      defibrotide should not be delayed after diagnosis of VOD/SOS.

PMID- 28444786
TI  - Targeted Photodynamic Therapy with a Folate/Sensitizer Assembly Produced from
      Mesoporous Silica.
AB  - A mesoporous silica material prepared by using folic acid (FA) as a template
      enables the effective encapsulation of meso-tetrakis(4-carboxyphenyl)porphyrin
      (TCPP) in its interior. Combination of steady-state and time-resolved absorption
      and emission spectroscopy demonstrate that FA and TCPP are released from the
      silica material to the aqueous phase in the form of a non-covalent assembly. This
      assembly does not form by simple mixing of the two components in the absence of
      silica, suggesting the key role of the material in the assembling process. The
      FA/TCPP assembly exhibits dual color fluorescence in the visible region, good
      photosensitization capability of singlet oxygen, and enhanced photo-induced
      mortality in KB cancer cells overexpressing folate receptor, if compared with the
      free components.

PMID- 28444787
TI  - Finger pressure adjustments to various object configurations during precision
      grip in humans and monkeys.
AB  - In this study, we recorded the pressure exerted onto an object by the index
      finger and the thumb of the preferred hand of 18 human subjects and either hand
      of two macaque monkeys during a precision grasping task. The to-be-grasped object
      was a custom-made device composed by two plates which could be variably oriented
      by a motorized system while keeping constant the size and thus grip dimension.
      The to-be-grasped plates were covered by an array of capacitive sensors to
      measure specific features of finger adaptation, namely pressure intensity and
      centroid location and displacement. Kinematic measurements demonstrated that for
      human subjects and for monkeys, different plate configurations did not affect
      wrist velocity and grip aperture during the reaching phase. Consistently, at the
      instant of fingers-plates contact, pressure centroids were clustered around the
      same point for all handle configurations. However, small pressure centroid
      displacements were specifically adopted for each configuration, indicating that
      both humans and monkeys can display finger adaptation during precision grip.
      Moreover, humans applied stronger thumb pressure intensity, performed less
      centroid displacement and required reduced adjustment time, as compared to
      monkeys. These pressure patterns remain similar when different load forces were
      required to pull the handle, as ascertained by additional measurements in humans.
      The present findings indicate that, although humans and monkeys share common
      features in motor control of grasping, they differ in the adjustment of fingertip
      pressure, probably because of skill and/or morphology divergences. Such a
      precision grip device may form the groundwork for future studies on prehension
      mechanisms.

PMID- 28444788
TI  - Night sleep in patients with vegetative state.
AB  - Polysomnographic recording of night sleep was carried out in 15 patients with the
      diagnosis vegetative state (syn. unresponsive wakefulness syndrome). Sleep
      scoring was performed by three raters, and confirmed by means of a spectral power
      analysis of the electroencephalogram, electrooculogram and electromyogram. All
      patients but one exhibited at least some signs of sleep. In particular, sleep
      stage N1 was found in 13 patients, N2 in 14 patients, N3 in nine patients, and
      rapid eye movement sleep in 10 patients. Three patients exhibited all phenomena
      characteristic for normal sleep, including spindles and rapid eye movements.
      However, in all but one patient, sleep patterns were severely disturbed as
      compared with normative data. All patients had frequent and long periods of
      wakefulness during the night. In some apparent rapid eye movement sleep episodes,
      no eye movements were recorded. Sleep spindles were detected in five patients
      only, and their density was very low. We conclude that the majority of vegetative
      state patients retain some important circadian changes. Further studies are
      necessary to disentangle multiple factors potentially affecting sleep pattern of
      vegetative state patients.

PMID- 28444789
TI  - Effect of dietary supplementation of hemp seed (Cannabis sativa L.) on meat
      quality and egg fatty acid composition of Japanese quail (Coturnix coturnix
      japonica).
AB  - This study was conducted in two separate experiments. Experiment I was conducted
      to investigate the effects of hemp seed (HS) on meat quality traits, and
      experiment II was designed to determine egg fatty acid (FA) composition in
      Japanese quail (Coturnix coturnix japonica). In experiment I and experiment II
      treatments, groups were as follows: (i) control (not included HS0), (ii) 5% HS
      inclusion to diets, (iii) 10% HS inclusion to diets and (iv) 20% HS inclusion to
      diets. In experiment I, a total of 192 7-day-old-quail were fed with HS diets for
      5 weeks, and end of the experiment I, a total of 64 quail (16 each) slaughtered
      and meat samples were analysed for meat colour, pH, cooking and thawing loss and
      FA composition. In experiment II, a total of 120 8-week-old laying quail were fed
      with experimental diets for 6 weeks and egg FA composition were determined.
      Breast meat cooking loss was significantly lower in 20% supplemented group (p <
      0.01). Hemp seed inclusion to diets caused a linear and cubic increase in redness
      (a*) of hip meat (p < 0.01). Palmitoleic and oleic FAs were decreased with HS
      addition in breast meat (p < 0.05); however, linoleic and linolenic acid contents
      of meat were linearly increased (p < 0.01). In experiment II, the linoleic and
      linolenic FA contents of egg samples were linearly increased with increasing the
      dietary HS ratio (p < 0.01). Hemp seed addition was provided lower palmitoleic
      and oleic FAs in quail eggs (p < 0.05). In conclusion, HS supplementation to
      quail diets may increase quail meat redness and meat and egg yolk omega-3 FA
      content and decrease cooking loss of quail meats.

PMID- 28444790
TI  - Aloe-emodin Induces Apoptosis in Human Liver HL-7702 Cells through Fas Death
      Pathway and the Mitochondrial Pathway by Generating Reactive Oxygen Species.
AB  - Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone) is one of the primary
      active compounds in total rhubarb anthraquinones isolated from some traditional
      medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce
      hepatotoxicity in rats. Thus, the aim of this study was to determine the
      potential cytotoxic effects and the underlying mechanism of aloe-emodin on human
      normal liver HL-7702 cells. The CCK-8 assays demonstrated that aloe-emodin
      decreased the viability of HL-7702 cells in a dose-dependent and time-dependent
      manner. Aloe-emodin induced S and G2/M phase cell cycle arrest in HL-7702 cells.
      This apoptosis was further investigated by flow cytometry and nuclear
      morphological changes by DAPI staining, respectively. Moreover, aloe-emodin
      provoked the production of intracellular reactive oxygen species and the
      depolarization of mitochondrial membrane potential (MMP). Further studies by
      western blot indicated that aloe-emodin dose-dependently up-regulated the levels
      of Fas, p53, p21, Bax/Bcl-2 ratio, and cleaved caspase-3, -8, -9, and subsequent
      cleavage of poly(ADP-ribose)polymerase (PARP). Taken together, these results
      suggest that aloe-emodin inhibits cell proliferation of HL-7702 cells and induces
      cell cycle arrest and caspase-dependent apoptosis via both Fas death pathway and
      the mitochondrial pathway by generating reactive oxygen species, indicating that
      aloe-emodin should be taken into account in the risk assessment for human
      exposure. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444791
TI  - Trialling nutrient recommendations for slow lorises (Nycticebus spp.) based on
      wild feeding ecology.
AB  - Slow loris (Nycticebus spp.) captive diets have been based on routine and
      anecdotes rather than scientific fact. The growing body of evidence contradicts
      the high fruit diet supported by such anecdotes. Non-human primate nutrient
      requirements are grouped into new (based on the common marmoset Callithrix
      jacchus) or old world (based on rhesus macaques Macaca mulatta) primates. Slow
      lorises are known to suffer from many health ailments in captivity such as dental
      disease, obesity, wasting and kidney issues all of which have been linked to
      diet. This study aimed to estimate nutrient intake from free-ranging slow lorises
      and to determine whether this intake can be used as nutrient recommendations. We
      collected data of nutrient intake, food passage rate and digestibility of captive
      slow lorises on three diet treatments 1: current captive type diet which is
      mostly fruits, 2: wild-type diet made only of food items from their natural diet,
      3: new diet made to reflect wild slow loris nutrient intake. In order to validate
      our nutrient recommendations, diets 2 and 3 would have to be significantly
      different to Diet 1 in terms of nutrients, but not different from each other.
      Captive diets were significantly higher in soluble carbohydrates and lower in
      minerals and fibre fractions than both diets 2 and 3. Diets 2 and 3 led to a
      significantly increased food passage time and to more effective fibre and calcium
      digestion compared to Diet 1. We also observed obese individuals lost weight and
      underweight individuals gained weight. Our nutrient recommendations have been
      validated by our trials, and new or old world monkey nutrient recommendations are
      not consistent with our results. Diets should be high in protein and fibre and
      low in soluble carbohydrates and fats.

PMID- 28444792
TI  - A computational approach to study functional monomer-protein molecular
      interactions to optimize protein molecular imprinting.
AB  - Molecular imprinting has become a promising approach for synthesis of polymeric
      materials having binding sites with a predetermined selectivity for a given
      analyte, the so-called molecularly imprinted polymers (MIPs), which can be used
      as artificial receptors in various application fields. Realization of binding
      sites in a MIP involves the formation of prepolymerization complexes between a
      template molecule and monomers, their subsequent polymerization, and the removal
      of the template. It is believed that the strength of the monomer-template
      interactions in the prepolymerization mixture influences directly on the quality
      of the binding sites in a MIP and consequently on its performance. In this study,
      a computational approach allowing the rational selection of an appropriate
      monomer for building a MIP capable of selectively rebinding macromolecular
      analytes has been developed. Molecular docking combined with quantum chemical
      calculations was used for modeling and comparing molecular interactions among a
      model macromolecular template, immunoglobulin G (IgG), and 1 of 3
      electropolymerizable functional monomers: m-phenylenediamine (mPD), dopamine, and
      3,4-ethylenedioxythiophene, as well as to predict the probable arrangement of
      multiple monomers around the protein. It was revealed that mPD was arranged more
      uniformly around IgG participating in multiple H-bond interactions with its polar
      residues and, therefore, could be considered as more advantageous for synthesis
      of a MIP for IgG recognition (IgG-MIP). These theoretical predictions were
      verified by the experimental results and found to be in good agreement showing
      higher binding affinity of the mPD-based IgG-MIP toward IgG as compared with the
      IgG-MIPs generated from the other 2 monomers.

PMID- 28444793
TI  - Dietary mannoheptulose does not alter glucose or lipid metabolism in adult
      Labrador Retrievers.
AB  - Mannoheptulose (MH), a glycolytic inhibitor, has been preliminarily investigated
      as a novel functional food ingredient for dogs. This study aimed to determine the
      effects of dietary MH, delivered as an extract of un-ripened avocados, on fatty
      acid and glucose kinetics in healthy adult Labrador Retriever dogs (n = 12 dogs).
      The study was a double-blindcrossover with each dog receiving both dietary
      treatments, control (CON) and MH (400 mg/kg of diet), in random order. Glucose
      and glycerol plasma turnover (Ra) and oxidation (Ox) were measured in fasting and
      in response to repeated meal feeding ("fed") with stable isotope tracers (U-13 C
      glucose, 1,1,2,3,3-D5 -glycerol) and indirect calorimetry. Palmitate Ra and Ox
      were examined during repeated meal feeding only using an oral bolus of U-13 C-K2 
      palmitate and indirect calorimetry. MH had no discernible effect on fasting
      glucose Ra (677, 722 SEM 36 MUmol/min, CON, MH) or Ox (107, 109 MUmol/min, CON,
      MH SEM 10 MUmol/min) or fed glucose Ra (2913, 3626 SEM 644 MUmol/min, CON, MH) or
      Ox (951, 936 SEM 174 MUmol/min, CON, MH). Glycerol Ra, an index of the rate of
      lipolysis, was not different between dietary treatments (Fast 162, 113 SEM 35
      MUmol/min CON, MH; Fed 172, 135 SEM 21 MUmol/min, CON, MH). Similarly, palmitate
      oxidation was not impacted by MH feeding (1966, 2276 SEM 79 MUmol/min, CON, MH).
      Together, these findings do not support MH as a novel functional food ingredient
      at least at the dietary dose tested.

PMID- 28444794
TI  - Protection of protein from ruminal degradation by alkali-induced oxidation of
      chlorogenic acid in sunflower meal.
AB  - Lactating ruminants require an adequate supply of absorbable amino acids for the
      synthesis of milk protein from two sources, that is crude protein (CP)
      synthesized microbially in the rumen and ruminally undegraded CP (RUP) from feed
      which can both be digested in the small intestine. Several chemical and physical
      methods have been identified as being effective in increasing the proportion of
      RUP of total CP of a feedstuff, yet there is a continuing need for developing and
      establishing methods which protect feed protein from ruminal degradation with
      acceptable expenditure of labour and other costs. The objective of this study was
      to identify and quantify effects of and interactions between chlorogenic acid and
      protein in solvent-extracted sunflower meal (SFM) as induced by alkali treatment.
      Response surface methodology was employed to investigate the influence of pH,
      reaction time and drying temperature on the resulting SFM and, subsequently, its
      protein value for ruminants estimated from laboratory values. For this purpose,
      alkali-treated SFM was subjected to a fractionation of feed CP according to the
      Cornell net carbohydrate and protein system as a basis for estimating RUP at
      different assumed ruminal passage rates (Kp ). To estimate the intestinal
      digestibility of the treated SFM and its RUP, a three-step enzymatic in vitro
      procedure was applied. Alkaline treatment of SFM increased RUP values with
      factors ranging from approximately 3 (Kp =.08/hr) to 12 (Kp =.02/hr).
      Furthermore, the intestinal digestibility of the alkali-treated SFM was enhanced
      by approximately 10% compared to untreated SFM. Increasing pH and reaction time
      led to both increasing RUP values and intestinal digestibility. In conclusion, a
      targeted alkaline treatment of naturally occurring compounds in feedstuffs might
      be a promising approach to provide high-RUP feeds for ruminants which, at the
      same time, have improved intestinal digestibility values.

PMID- 28444795
TI  - Systematics and Molecular Phylogeny of the Ciliate Genus Pseudokeronopsis
      (Ciliophora, Hypotrichia).
AB  - A still challenging study on ciliate systematics is to clarify the taxonomic and
      phylogenetic confusions of the fascinating pigmented Pseudokeronopsis species
      because of their high interspecific similarities. We evaluated the identities and
      internal relationships within Pseudokeronopsis based on morphological
      descriptions in combination with the 18S and ITS-5.8S rDNA genetic distances,
      ITS2 secondary structures and phylogenetic analyses. Results showed that (1)
      Pseudokeronopsis pararubra, a species ever synonymized as Pseudokeronopsis
      carnea, is a valid species; (2) most Chinese populations identified as
      Pseudokeronopsis rubra represent a new species namely Pseudokeronopsis songi sp.
      nov.; (3) within Pseudokeronopsis, P. carnea branched early, while P. songi sp.
      nov., P. flava, and P. erythrina showed close relationships and formed a sister
      clade with P. pararubra; (4) compared to 18S and ITS2 rDNA, ITS-5.8S rDNA is more
      suitable for separating Pseudokeronopsis species, with pairwise distances of 0
      0.0441 at the intraspecific level and 0.0635-0.1150 at the interspecific level;
      and (5) the core structure of Pseudokeronopsis ITS2 includes three helices, with
      helix III being the longest and showing an identical pattern in conspecific
      populations and small differences among species. Based on the evaluation, we
      clarify all misidentified and dubious 18S and ITS-5.8S rDNA sequences of
      Pseudokeronopsis in GenBank.

PMID- 28444796
TI  - Determination of Volatile Flavour Profiles of Citrus spp. Fruits by SDE-GC-MS and
      Enantiomeric Composition of Chiral Compounds by MDGC-MS.
AB  - INTRODUCTION: Citrus fruits are known to have characteristic enantiomeric key
      compounds biosynthesised by highly stereoselective enzymatic mechanisms. In the
      past, evaluation of the enantiomeric ratios of chiral compounds in fruits has
      been applied as an effective indicator of adulteration by the addition of
      synthetic compounds or natural components of different botanical origin.
      OBJECTIVE: To analyse the volatile flavour compounds of Citrus junos Sieb. ex
      Tanaka (yuzu), Citrus limon BURM. f. (lemon) and Citrus aurantifolia Christm.
      Swingle (lime), and determine the enantiomeric ratios of their chiral compounds
      for discrimination and authentication of extracted oils. METHODOLOGY: Volatile
      flavour compounds of the fruits of the three Citrus species were extracted by
      simultaneous distillation extraction and analysed by gas chromatography-mass
      spectrometry. The enantiomeric composition (ee%) of chiral camphene, sabinene,
      limonene and beta-phellandrene was analysed by heart-cutting multidimensional gas
      chromatography-mass spectrometry. RESULTS: Sixty-seven (C. junos), 77 (C. limon)
      and 110 (C. aurantifolia) volatile compounds were identified with limonene, gamma
      terpinene and linalool as the major compounds. Stereochemical analysis (ee%)
      revealed 1S,4R-(-) camphene (94.74, 98.67, 98.82), R-(+)-limonene (90.53, 92.97,
      99.85) and S-(+)-beta-phellandrene (98.69, 97.15, 92.13) in oil samples from all
      three species; R-(+)-sabinene (88.08) in C. junos; and S-(-)-sabinene (81.99,
      79.74) in C. limon and C. aurantifolia, respectively. CONCLUSION: The
      enantiomeric composition and excess ratios of the chiral compounds could be used
      as reliable indicators of genuineness and quality assurance of the oils derived
      from the Citrus fruit species. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444797
TI  - The transcription factor MYB115 contributes to the regulation of proanthocyanidin
      biosynthesis and enhances fungal resistance in poplar.
AB  - Proanthocyanidins (PAs) are major defense phenolic compounds in the leaves of
      poplar (Populus spp.) in response to abiotic and biotic stresses. Transcriptional
      regulation of PA biosynthetic genes by the MYB-basic helix-loop-helix (bHLH)-WD40
      complexes in poplar is not still fully understood. Here, an Arabidopsis TT2-like
      gene MYB115 was isolated from Populus tomentosa and characterized by various
      molecular, genetic and biochemical approaches. MYB115 restored PA productions in
      the seed coat of the Arabidopsis tt2 mutant. Overexpression of MYB115 in poplar
      activated expression of PA biosynthetic genes, resulting in a significant
      increase in PA concentrations. By contrast, the CRISPR/Cas9-generated myb115
      mutant exhibited reduced PA content and decreased expression of PA biosynthetic
      genes. MYB115 directly activated the promoters of PA-specific structural genes.
      MYB115 interacted with poplar TT8. Coexpression of MYB115, TT8 and poplar TTG1
      significantly enhanced the expression of ANR1 and LAR3. Additionally, transgenic
      plants overexpressing MYB115 had increased resistance to the fungal pathogen
      Dothiorella gregaria, whereas myb115 mutant exhibited greater sensitivity
      compared with wild-type plants. Our data provide insight into the regulatory
      mechanisms controlling PA biosynthesis by MYB115 in poplar, which could be
      effectively employed for metabolic engineering of PAs to improve resistance to
      fungal pathogens.

PMID- 28444798
TI  - Multi-gel casting apparatus for vertical polyacrylamide gels with in-built
      solution flow system and liquid level detectors.
AB  - PAGE is the most widely used technique for the separation and biochemical
      analysis of biomolecules. The ever growing field of proteomics and genomics
      necessitates the analysis of many proteins and nucleic acid samples to understand
      further about the structure and function of cells. Simultaneous analysis of
      multiple protein samples often requires casting of many PAGE gels. Several
      variants of multi-gel casting/electrophoresis apparatuses are frequently used in
      research laboratories. Requirement of supplementary gels to match the growing
      demand for analyzing additional protein samples sometimes become a cause of
      concern. Available apparatuses are not amenable to and therefore, not recommended
      for any modification to accommodate additional gel casting units other than what
      is prescribed by the manufacturer. A novel apparatus is described here for
      casting multiple PAGE gels comprising four detachable components that provide
      enhanced practicability and performance of the apparatus. This newly modified
      apparatus promises to be a reliable source for making multiple gels in less time
      without hassle. Synchronized functioning of unique components broaden the
      possibilities of developing inexpensive, safe, and time-saving multi-gel casting
      apparatus. This apparatus can be easily fabricated and modified to accommodate
      desired number of gel casting units. The estimated cost (~$300) for fabrication
      of the main apparatus is very competitive and effortless assembly procedure can
      be completed within ~30 min.

PMID- 28444799
TI  - Pixel-wise estimation of noise statistics on iterative CT reconstruction from a
      single scan.
AB  - PURPOSE: As iterative CT reconstruction continues to advance, the spatial
      distribution of noise standard deviation (STD) and accurate noise power spectrum
      (NPS) on the reconstructed CT images become important for method evaluation as
      well as optimization of algorithm parameters. Using a single CT scan, we propose
      a practical method for pixel-wise calculation of noise statistics on an
      iteratively reconstructed CT image, which enables accurate calculation of noise
      STD for each pixel and NPS. METHOD: We first derive the noise propagation from
      measured projections to an iteratively reconstructed CT image provided that the
      projection noise is known. We then show that the model of noise propagation
      remains approximately unchanged for extra simulated noise added on the measured
      projections. To compute the noise STD map and the NPS map on an iteratively
      reconstructed CT image from a single scan, we first iteratively reconstruct the
      CT image from the measured projections using an existing reconstruction
      algorithm. The same measured projections are added by different sets (a total of
      32 sets in our implementation) of projection noise simulated from an estimated
      projection noise model, and are then used to iteratively reconstruct different CT
      images. The calculations of the noise STD map and the NPS map are finally
      performed on the entire stack of these different reconstruction images. RESULTS:
      We evaluate our method on an anthropomorphic head phantom, and demonstrate the
      clinical utility on a set of head and neck patient CT data, using two iterative
      CT reconstruction algorithms: the penalized weighted least-square (PWLS)
      algorithm and the total-variation (TV) regularization. In the head phantom case,
      repeated scans are acquired to generate the ground truths of noise STD and NPS
      maps. Using only one single scan, the proposed method accurately calculates the
      noise STD maps with a root-mean-square error (RMSE) of less than 5HU. In the NPS
      map estimation, we compare the result of our proposed method with that of the
      conventional method which calculates the NPS maps on a uniform region of interest
      on one CT image. Our method outperforms the conventional method on the NPS map
      estimation with RMSE reduced by 92%. The implementation of the proposed method on
      the patient data successfully provides the noise STD values around complex
      structures and a high-quality NPS map. CONCLUSION: The proposed method accurately
      calculates noise STD for each pixel and NPS on an iteratively reconstructed CT
      image, with no requirement of repeated CT scans. It provides a detailed
      evaluation of imaging performance of different iterative reconstruction methods
      on the same CT dataset.

PMID- 28444800
TI  - Endoscopic meatus scoring scale versus sniff test to predict insertability before
      transnasal endoscopy: A prospective, randomized study.
AB  - BACKGROUND AND AIM: Sniff test is a common method before unsedated transnasal
      esophago-gastro-duodenoscopy (UT-EGD) to select a nostril insertion site. Yet
      there is no objective method to select a more specific meatus insertion tract for
      anesthesia and insertion. We devised an endoscopic meatus scoring scale by
      anterior meatuscopy to select the most optimal meatus insertion tract. We
      hypothesized that meatuscopy instead of sniff test might improve tolerance and
      reduce adverse events during nasal anesthesia and UT-EGD. METHODS: A prospective
      randomized controlled trial to compare patient tolerance and adverse events.
      RESULTS: A total of 359 patients were assessed and finally 310 patients were
      analyzed. There were no statistical differences in patient characteristics and
      insertion failure rates. Pain scores during nasal anesthesia, nasal
      insertion/exsertion, UT-EGD, and overall tolerance were significantly lower in
      the meatuscopy group than sniff test group. Compared with the sniff tested
      patients, the meatuscopied patients had significantly lower epistaxis rates
      during insertion/exsertion, better visual capacity after decongestive anesthesia,
      and shorter total procedure time. A significantly higher proportion of the
      meatuscopied than sniff tested patients would like to receive the same procedure
      next time. Nasal discharge, nasal pain, epistaxis, and blowing out blood clots
      occurred significantly less frequent in the meatuscopy group than sniff test
      group. More sniff tested than meatuscopied patients had headache, delayed
      epistaxis, and sinusitis although they were not statistically significant.
      CONCLUSION: Selection of an optimal meatus insertion tract by an anterior
      meatuscopy causes lesser nasal pain, epistaxis, and post-procedural side effects
      in nasal anesthesia and UT-EGD than the conventional sniff test.

PMID- 28444801
TI  - Comprehensive identification and structural characterization of target components
      from Gelsemium elegans by high-performance liquid chromatography coupled with
      quadrupole time-of-flight mass spectrometry based on accurate mass databases
      combined with MS/MS spectra.
AB  - This study reports an applicable analytical strategy of comprehensive
      identification and structure characterization of target components from Gelsemium
      elegans by using high-performance liquid chromatography quadrupole time-of-flight
      mass spectrometry (LC-QqTOF MS) based on the use of accurate mass databases
      combined with MS/MS spectra. The databases created included accurate masses and
      elemental compositions of 204 components from Gelsemium and their structural
      data. The accurate MS and MS/MS spectra were acquired through data-dependent auto
      MS/MS mode followed by an extraction of the potential compounds from the LC-QqTOF
      MS raw data of the sample. The same was matched using the databases to search for
      targeted components in the sample. The structures for detected components were
      tentatively characterized by manually interpreting the accurate MS/MS spectra for
      the first time. A total of 57 components have been successfully detected and
      structurally characterized from the crude extracts of G. elegans, but has failed
      to differentiate some isomers. This analytical strategy is generic and efficient,
      avoids isolation and purification procedures, enables a comprehensive structure
      characterization of target components of Gelsemium and would be widely applicable
      for complicated mixtures that are derived from Gelsemium preparations. Copyright
      (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444802
TI  - Eddy current-nulled convex optimized diffusion encoding (EN-CODE) for distortion
      free diffusion tensor imaging with short echo times.
AB  - PURPOSE: To design and evaluate eddy current-nulled convex optimized diffusion
      encoding (EN-CODE) gradient waveforms for efficient diffusion tensor imaging
      (DTI) that is free of eddy current-induced image distortions. METHODS: The EN
      CODE framework was used to generate diffusion-encoding waveforms that are eddy
      current-compensated. The EN-CODE DTI waveform was compared with the existing eddy
      current-nulled twice refocused spin echo (TRSE) sequence as well as monopolar
      (MONO) and non-eddy current-compensated CODE in terms of echo time (TE) and image
      distortions. Comparisons were made in simulations, phantom experiments, and neuro
      imaging in 10 healthy volunteers. RESULTS: The EN-CODE sequence achieved eddy
      current compensation with a significantly shorter TE than TRSE (78 versus 96 ms)
      and a slightly shorter TE than MONO (78 versus 80 ms). Intravoxel signal variance
      was lower in phantoms with EN-CODE than with MONO (13.6 +/- 11.6 versus 37.4 +/-
      25.8) and not different from TRSE (15.1 +/- 11.6), indicating good robustness to
      eddy current-induced image distortions. Mean fractional anisotropy values in
      brain edges were also significantly lower with EN-CODE than with MONO (0.16 +/-
      0.01 versus 0.24 +/- 0.02, P < 1 x 10-5 ) and not different from TRSE (0.16 +/-
      0.01 versus 0.16 +/- 0.01, P = nonsignificant). CONCLUSIONS: The EN-CODE sequence
      eliminated eddy current-induced image distortions in DTI with a TE comparable to
      MONO and substantially shorter than TRSE. Magn Reson Med 79:663-672, 2018. (c)
      2017 International Society for Magnetic Resonance in Medicine.

PMID- 28444803
TI  - Fear of pain changes movement: Motor behaviour following the acquisition of pain
      related fear.
AB  - BACKGROUND: According to current fear-avoidance models, changes in motor
      behaviour (e.g. avoidance) are a key component in the development and maintenance
      of chronic pain complaints. Yet, experimental research assessing actual
      behavioural changes following painful events is relatively sparse. This study
      investigated the effects of pain anticipation on changes in motor behaviour using
      a fear conditioning paradigm and robot-generated standardized movement
      trajectories of the upper extremities. METHODS: Pain-free participants (N = 20)
      performed clockwise and counterclockwise fixed, circular movements with a robotic
      arm without receiving visual feedback. During fear acquisition, moving in one
      direction (CS+) was paired with a painful stimulus (pain-US) whereas moving in
      the other direction (CS-) was not. During the subsequent extinction phase, the
      pain-US was omitted. We assessed self-reported pain-related fear and urge to
      avoid the movement, as well as several behavioural measures: Velocity,
      acceleration, exerted force and force direction. RESULTS: Movements that were
      paired with pain were associated with increased self-reported pain-related fear
      and urge to avoid. Moreover, movements that were associated with pain were
      performed faster, more forcefully and more accurately than movements that were
      not associated with pain. All these differences diminished during the extinction
      phase. CONCLUSIONS: The present study demonstrates the utility of robot-generated
      force feedback in the study of pain-related fear and associated changes in motor
      behaviour. SIGNIFICANCE: Fear of pain changes movement: Movements associated with
      pain are performed faster, with more force and higher accuracy than movements
      that are not associated with pain. These changes can inform us how fear of pain
      translates into avoidance and escape behaviour, two important constructs in the
      maintenance of chronic pain.

PMID- 28444805
TI  - 2D multi-spectral imaging for fast MRI near metal.
AB  - PURPOSE: To develop a fast 2D method for MRI near metal with reduced B0 in-plane
      and through-slice artifacts. METHODS: Multi-spectral imaging (MSI) approaches
      reduce artifacts in MR images near metal, but require 3D imaging of multiple
      excited volumes regardless of imaging geometry or artifact severity. The proposed
      2D MSI method rapidly excites a limited slice and spectral region using gradient
      reversal between excitation and refocusing pulses, then uses standard 2D imaging,
      with the process repeating to cover multiple spectral offsets that are combined
      as in other MSI techniques. 2D MSI was implemented in a spin-echo-train sequence
      and validated in phantoms and in vivo by comparing it with standard spin-echo
      imaging and existing MSI techniques. RESULTS: 2D MSI images for each spatial
      spectral region follow isocontours of the dipole-like B0 field variation, and
      thus frequency variation, near metal devices. Artifact correction in phantoms and
      human subjects with metal is comparable to 3D MSI methods, and superior to
      standard spin-echo techniques. Scan times are reduced compared with 3D MSI
      methods in cases where a limited number of slices are needed, though signal-to
      noise ratio is also reduced as expected. CONCLUSION: 2D MSI offers a fast and
      flexible alternative to 3D MSI for artifact reduction near metal. Magn Reson Med
      79:968-973, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 28444804
TI  - Effect of resistant starch on the intestinal health of old dogs: fermentation
      products and histological features of the intestinal mucosa.
AB  - The effects of resistant starch (RS) intake on nutrient digestibility, microbial
      fermentation products, faecal IgA, faecal pH, and histological features of the
      intestinal mucosa of old dogs were evaluated. The same formulation was extruded
      in two different conditions: one to obtain elevated starch cooking degree with
      low RS content (0.21%) and the other lower starch cooking with high RS content
      (1.46%). Eight geriatric Beagles (11.5 +/- 0.38 years old) were fed each diet for
      61 days in a crossover design. Food intake, nutrient digestibility, fermentation
      products, faecal pH, and faecal IgA were examined via variance analysis.
      Histological results of intestinal biopsies were assessed via Wilcoxon test for
      paired data. The morphometric characteristics of large intestine crypts were
      evaluated via paired t tests (p < .05). Protein, fat, and energy digestibilities
      were higher for the low-RS diet (p < .05). Dogs receiving the high-RS diet had
      lower faecal pH and higher values for propionate, butyrate, total volatile fatty
      acids, and lactate (p < .05). No differences between diets were found in the
      histological parameters of the gut mucosa, and only a tendency for deeper crypts
      in the descending colon was observed for dogs fed the high-RS diet (p = .083).
      The intake of a corn-based kibble diet manufactured with coarse ground raw
      material and low starch gelatinization to obtain 1.4% of RS affected microbial
      fermentation products and faecal pH and tended to increase crypt depth in the
      descending colon of old dogs.

PMID- 28444806
TI  - Swine foetal myogenesis in different gestation periods.
AB  - This experiment was conducted to evaluate the effects of sex and uterus position
      on swine foetal myogenesis at different gestational ages. Fifteen primiparous
      sows were divided into three groups according to gestational age: 50, 80, and 106
      days. The experiment was a block randomized factorial design with two sexes (male
      and female) and three uterine regions (apex, middle, and base). After slaughter,
      each uterus horn was divided into three segments of equal length: apex region
      near the ovary; base region near the uterine body; and the middle region, lying
      between the apex and base regions. The foetuses were weighed, identified, and
      longitudinally opened to harvest the semitendinosus muscle for later
      morphological analysis. After 50 days of pregnancy, male foetuses had greater (p
      < .05) weight than females. The number of primary fibres at 50 days of gestation
      was negatively correlated (r = -.29, p = .04) with the number of foetuses in
      utero. After 80 days, foetuses in the base region had less (p < .05) secondary
      area of muscle fibres compared to the apex region, which was accompanied by
      differences in the weight of the foetuses, the lowest weight were for foetuses
      located in the base region (p < .05). In the same period, the ratio of secondary
      to primary fibres had a positive correlation with weight. In conclusion, sex did
      not influence myogenesis in the gestational ages studied and the development of
      secondary muscle fibres of the foetuses at 80 days of gestation was affected by
      their uterine position with foetuses at the base of the uterine horn being less
      developed.

PMID- 28444808
TI  - Fast and Simple Discriminative Analysis of Anthocyanins-Containing Berries Using
      LC/MS Spectral Data.
AB  - INTRODUCTION: Anthocyanins are potent antioxidant agents that protect against
      many degenerative diseases; however, they are unstable because they are
      vulnerable to external stimuli including temperature, pH and light. This
      vulnerability hinders the quality control of anthocyanin-containing berries using
      classical high-performance liquid chromatography (HPLC) analytical methodologies
      based on UV or MS chromatograms. OBJECTIVE: To develop an alternative approach
      for the quality assessment and discrimination of anthocyanin-containing berries,
      we used MS spectral data acquired in a short analytical time rather than UV or MS
      chromatograms. METHOD: Mixtures of anthocyanins were separated from other
      components in a short gradient time (5 min) due to their higher polarity, and the
      representative MS spectrum was acquired from the MS chromatogram corresponding to
      the mixture of anthocyanins. RESULTS: The chemometric data from the
      representative MS spectra contained reliable information for the identification
      and relative quantification of anthocyanins in berries with good precision and
      accuracy. CONCLUSION: This fast and simple methodology, which consists of a
      simple sample preparation method and short gradient analysis, could be applied to
      reliably discriminate the species and geographical origins of different
      anthocyanin-containing berries. These features make the technique useful for the
      food industry. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444809
TI  - Retrospective review of routine clinical patient experiences with dolutegravir;
      virological suppression, immunological recovery and adverse events.

PMID- 28444807
TI  - Raf kinase inhibitor protein: lessons of a better way for beta-adrenergic
      receptor activation in the heart.
AB  - Stimulation of beta-adrenergic receptors (betaARs) provides the most efficient
      physiological mechanism to enhance contraction and relaxation of the heart.
      Activation of betaARs allows rapid enhancement of myocardial function in order to
      fuel the muscles for running and fighting in a fight-or-flight response.
      Likewise, betaARs become activated during cardiovascular disease in an attempt to
      counteract the restrictions of cardiac output. However, long-term stimulation of
      betaARs increases the likelihood of cardiac arrhythmias, adverse ventricular
      remodelling, decline of cardiac performance and premature death, thereby limiting
      the use of betaAR agonists in the treatment of heart failure. Recently the
      endogenous Raf kinase inhibitor protein (RKIP) was found to activate betaAR
      signalling of the heart without adverse effects. This review will summarize the
      current knowledge on RKIP-driven compared to receptor-mediated signalling in
      cardiomyocytes. Emphasis is given to the differential effects of RKIP on beta1 -
      and beta2 -ARs and their downstream targets, the regulation of myocyte calcium
      cycling and myofilament activity.

PMID- 28444810
TI  - Large differences in proportions of harmful and benign amino acid substitutions
      between proteins and diseases.
AB  - Genes and proteins are known to have differences in their sensitivity to
      alterations. Despite numerous sequencing studies, proportions of harmful and
      harmless substitutions are not known for proteins and groups of proteins. To
      address this question, we predicted the outcome for all possible single amino
      acid substitutions (AASs) in nine representative protein groups by using the PON
      P2 method. The effects on 996 proteins were studied and vast differences were
      noticed. Proteins in the cancer group harbor the largest proportion of harmful
      variants (42.1%), whereas the non-disease group of proteins not known to have a
      disease association and not involved in the housekeeping functions had the lowest
      number of harmful variants (4.2%). Differences in the proportions of the harmful
      and benign variants are wide within each group, but they still show clear
      differences between the groups. Frequently appearing protein domains show a wide
      spectrum of variant frequencies, whereas no major protein structural class
      specific differences were noticed. AAS types in the original and variant residues
      showed distinctive patterns, which are shared by all the protein groups. The
      observations are relevant for understanding genetic bases of diseases, variation
      interpretation, and for the development of methods for that purpose.

PMID- 28444811
TI  - Three-year income trends in Korean adults commencing haemodialysis: A prospective
      cohort.
AB  - AIM: This study aimed to explore the trends in individual income and to estimate
      the change in average monthly income for patients undergoing haemodialysis
      therapy. METHODS: The main data source was the Clinical Research Center (CRC) for
      End-Stage Renal Disease in Korea. In addition to the cohort data, a survey was
      conducted to capture personal income for 3 years. To estimate the change in
      monthly income over time using repeated measures, a random coefficient model
      using penalized quasi-likelihood methods based on restricted or residual maximum
      likelihood estimation was used. RESULTS: During the 3-year study period, 138
      subjects aged 20 and over who answered the question about pre-dialysis income
      were traced and analyzed. The median value of monthly income was $US564.4 in the
      1st year, $470.4 in the 2nd year, and $733.8 in the 3rd year, representing a 70%,
      75%, and 61% decrease compared to pre-dialysis income ($1881.5), respectively. By
      using mixed analysis, we found that monthly income change was $1283 (95% CI, 
      1621.5, -945.1), $1182 USD (95% CI, -1540.8, -823.1), and $1041 (95% CI, -1457.6,
      -623.6) in the 1st , 2nd , and 3rd year, respectively, compared to pre-dialysis
      income after controlling for other covariates. Women and less educated patients
      had a relatively higher reduction of income, despite the low starting point.
      CONCLUSIONS: The monthly income of dialysis patients reduced substantially over
      the study period, especially at the time of the first survey. Considering the
      social security system, haemodialysis patients face significant personal
      financial burdens due to their ESRD unrelated to the direct costs of dialysis
      treatment.

PMID- 28444812
TI  - A survey on abnormal uterine bleeding among radiographers with frequent MRI
      exposure using intrauterine contraceptive devices.
AB  - PURPOSE: Based on a previous case report of menometrorrhagia (prolonged/excessive
      uterine bleeding, occurring at irregular and/or frequent intervals) in MRI
      workers with intrauterine devices (IUDs), it was evaluated whether this
      association could be confirmed. METHODS: A survey was performed among 381 female
      radiographers registered with their national association. Logistic regression was
      used to analyze associations of abnormal uterine bleeding with the frequency of
      working with MRI scanners, presence near the scanner/in the scanner room during
      image acquisition, and with scanner strength or type. RESULTS: A total of 68
      women reported using IUDs, and 72 reported abnormal uterine bleeding. Compared
      with unexposed women not using IUDs, the odds ratio in women with IUDs working
      with MRI scanners was 2.09 (95% confidence interval 0.83-3.66). Associations were
      stronger if women working with MRI reported being present during image
      acquisition (odds ratio 3.43, 95% CI 1.26-9.34). Associations with scanner
      strength or type were not consistent. CONCLUSIONS: Radiographers using IUDs who
      are occupationally exposed to stray fields from MRI scanners report abnormal
      uterine bleeding more often than their co-workers without an IUD, or nonexposed
      co-workers with an IUD. In particular, radiographers present inside the scanner
      room during image acquisition showed an increased risk. Magn Reson Med 79:1083
      1089, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 28444813
TI  - Optimism and positive and negative feelings in parents of young children with
      developmental delay.
AB  - BACKGROUND: Parents' positive and negative feelings about their young children
      influence both parenting behaviour and child problem behaviour. Research has not
      previously examined factors that contribute to positive and negative feelings in
      parents of young children with developmental delay (DD). METHOD: The present
      study sought to examine whether optimism, a known protective factor for parents
      of children with DD, was predictive of positive and negative feelings for these
      parents. Data were collected from 119 parents of preschool-aged children with
      developmental delay. Two separate hierarchical linear regression analyses were
      conducted to determine if optimism significantly predicted positive feelings and
      negative feelings and whether optimism moderated relations between parenting
      stress and parent feelings. RESULTS: Increased optimism was found to predict
      increased positive feelings and decreased negative feelings after controlling for
      child problem behaviour and parenting stress. In addition, optimism was found to
      moderate the relation between parenting stress and positive feelings. CONCLUSION:
      Results suggest that optimism may impact how parents perceive their children with
      DD. Future research should examine how positive and negative feelings impact
      positive parenting behaviour and the trajectory of problem behaviour specifically
      for children with DD.

PMID- 28444815
TI  - Endoscopic findings following retroperitoneal pancreas transplantation.
AB  - AIM: An evaluation of the efficacy of endoscopic methods for the diagnosis and
      correction of surgical and immunological complications after retroperitoneal
      pancreas transplantation. MATERIALS AND METHODS: From October 2011 to March 2015,
      27 patients underwent simultaneous retroperitoneal pancreas-kidney
      transplantation (SPKT). Diagnostic oesophagogastroduodenoscopy (EGD) with
      protocol biopsy of the donor and recipient duodenal mucosa and endoscopic
      retrograde pancreatography (ERP) were performed to detect possible complications.
      Endoscopic stenting of the main pancreatic duct with plastic stents and three
      stage endoscopic hemostasis were conducted to correct the identified
      complications. RESULTS: Endoscopic methods showed high efficiency in the timely
      diagnosis and adequate correction of complications after retroperitoneal pancreas
      transplantation.

PMID- 28444814
TI  - Chronic Antibody-Mediated Rejection in Nonhuman Primate Renal Allografts:
      Validation of Human Histological and Molecular Phenotypes.
AB  - Molecular testing represents a promising adjunct for the diagnosis of antibody
      mediated rejection (AMR). Here, we apply a novel gene expression platform in
      sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP)
      renal transplants. We analyzed 34 previously described gene transcripts related
      to AMR in humans in 197 archival NHP samples, including 102 from recipients that
      developed chronic AMR, 80 from recipients without AMR, and 15 normal native
      nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10
      fold cross-validation receiver operating characteristic curve analysis,
      demonstrated excellent discrimination between AMR and non-AMR samples (area under
      the curve = 0.92). This three-gene set correlated with classic features of AMR,
      including glomerulitis, capillaritis, glomerulopathy, C4d deposition, and DSAs (r
      = 0.39-0.63, p < 0.001). Principal component analysis confirmed the association
      between three-gene set expression and AMR and highlighted the ambiguity of v
      lesions and ptc lesions between AMR and T cell-mediated rejection (TCMR).
      Elevated three-gene set expression corresponded with the development of
      immunopathological evidence of rejection and often preceded it. Many recipients
      demonstrated mixed AMR and TCMR, suggesting that this represents the natural
      pattern of rejection. These data provide NHP animal model validation of recent
      updates to the Banff classification including the assessment of molecular markers
      for diagnosing AMR.

PMID- 28444817
TI  - Microtubule stabilization promoted axonal regeneration and functional recovery
      after spinal root avulsion.
AB  - A spinal root avulsion injury disconnects spinal roots with the spinal cord. The
      rampant motoneuron death, inhibitory CNS/PNS transitional zone (TZ) for axonal
      regrowth and limited regeneration speed together lead to motor dysfunction.
      Microtubules rearrange to assemble a new growth cone and disorganized
      microtubules underline regeneration failure. It has been shown that microtubule
      stabilizing drug, Epothilone B, enhanced axonal regeneration and attenuated
      fibrotic scaring after spinal cord injury. Here, we are reporting that after
      spinal root avulsion+ re-implantation in adult rats, EpoB treatment improved
      motor functional recovery and potentiated electrical responses of motor units. It
      facilitated axons to cross the TZ and promoted more and bigger axons in the
      peripheral nerve. Neuromuscular junctions were reformed with better preserved
      postsynaptic structure, and muscle atrophy was prevented by EpoB administration.
      Our study showed that EpoB was a promising therapy for promoting axonal
      regeneration after peripheral nerve injury.

PMID- 28444818
TI  - Reduced community viral load does not coincide with a reduction in the rate of
      new HIV diagnoses and recent infections: data from a region of southern Italy.
AB  - OBJECTIVES: We assessed whether changes in community viral load (CVL) over time
      were associated with the rate of new HIV diagnoses (NDs). METHODS: HIV-1-positive
      individuals referred to our institute and permanently residing in our province
      were considered for inclusion in the study. A total of 861 HIV-infected adults
      with at least one HIV RNA measurement (12 530 measurements in total) between 2008
      and 2014 were included. Viraemia copy-years were calculated from all HIV RNA
      values for each patient using the trapezoidal rule; multiple CVL indicators were
      considered. Total NDs and recent infections (< 1 year) were analysed separately.
      The association between NDs and CVL was tested by means of mixed Poisson models,
      with CVL as a fixed effect and year as a random effect. RESULTS: The incidence of
      NDs was 2.28 per 100 000 residents in 2008 and 2.52 per 100 000 residents in
      2014. Total numbers of NDs and recent infections did not vary significantly over
      time (P for trend 0.879 and 0.39, respectively). Mean HIV RNA decreased from 31
      095.8 HIV-1 RNA copies/mL in 2008 to 21 231.5 copies/mL in 2014 (P < 0.001); a
      downward trend was always observed regardless of the CVL indicator considered.
      Depending on the indicator, there were some differences in CVL by patient
      characteristics. The most substantial contributors to CVL appeared to be male
      individuals, men who have sex with men (MSM), non-Italians, and untreated
      subjects (all P < 0.05). The relative risk of ND increased among Italians and MSM
      with an increasing proportion of subjects having an undetectable HIV RNA, and
      decreased in the same population with increasing levels of CVL. CONCLUSIONS: In
      our setting, CVL represented a good marker of access to care and treatment;
      however, reduced CVL did not coincide with a reduction in the rate of NDs.

PMID- 28444816
TI  - Efficacy and safety of dolutegravir and rilpivirine dual therapy as a
      simplification strategy: a cohort study.

PMID- 28444819
TI  - Antenatal maternal hepatitis B care is a predictor of timely perinatal
      administration of hepatitis B immunoglobulin.
AB  - BACKGROUND: Mother-to-child transmission of hepatitis B virus continues to occur
      despite universal recommendations for neonatal immune prophylaxis therapy (IPT)
      and infant vaccination. AIM: To characterise the risk factors for failure to
      provide timely IPT and completion of the infant hepatitis B vaccination schedule
      for children born to mothers with chronic hepatitis B (CHB). METHODS: We
      conducted a retrospective cohort study to assess compliance with universal
      guidelines for neonatal IPT for children born to CHB mothers at Monash Health,
      Australia from 2008 to 2013. These mothers were invited to participate in a
      telephone interview regarding post-partum hepatitis B virus (HBV) care and infant
      vaccination status. Multivariate logistic regression analysis was utilised to
      identify the predictors for engagement with specialist HBV care, timely
      administration of IPT, completion of HBV vaccination schedule and serological
      testing of the baby. RESULTS: A total of 451 CHB mothers delivered 454 live
      births. HBV immunoglobulin (HBIg) was dispensed within 12 h in 79.52% of births.
      HBIg was not administered to eight neonates. Of the 451 women, 125 were
      interviewed: 88.8% of babies completed the vaccine schedule, and 19.2% of infants
      had post-vaccination testing. Antenatal HBV care was independently associated
      with a greater likelihood of timely HBIg administration (odds ratio 1.64, P =
      0.04, 95% CI: 1.03-2.61). There were no significant predictors for engagement
      with specialist HBV care, vaccine coverage or serological testing of the baby.
      CONCLUSION: Targeted interventions to improve timely HBIg and completion of the
      vaccine schedule are recommended. All pregnant women with CHB should be referred
      for HBV-specific antenatal care regardless of viral replicative status.

PMID- 28444820
TI  - Casticin impairs cell migration and invasion of mouse melanoma B16F10 cells via
      PI3K/AKT and NF-kappaB signaling pathways.
AB  - Casticin, a polymethoxyflavone, is one of the major active components obtained
      from Fructus viticis, which have been shown to have anticancer activities
      including induce cell apoptosis in human cancer cells. The aim of this study was
      to investigate the molecular mechanisms by which casticin inhibits cell migration
      and invasion of mouse melanoma B16F10 cells. Cell viability was examined by MTT
      assay and the results indicated that casticin decreased the total percentages of
      viable cells in dose-dependent manners. Casticin affected cell migration and
      invasion in B16F10 cells were examined by wound healing mobility assay and Boyden
      chamber migration and invasion assay and results indicated that casticin
      inhibited cell migration and invasion in dose-dependent manners. Western blotting
      was used to examine the protein expression of B16F10 cells after exposed to
      casticin and the results showed that casticin decreased the expressions of MMP-9,
      MMP-2, MMP-1, FAK, 14-3-3, GRB2, Akt, NF-kappaB p65, SOS-1, p-EGFR, p-JNK 1/2,
      uPA, and Rho A in B16F10 cells. Furthermore, cDNA microarray assay was used to
      show that casticin affected associated gene expression of cell migration and
      invasion and the results indicated that casticin affected some of the gene
      expression such as increased SCN1B (cell adhesion molecule 1) and TIMP2 (TIMP
      metallopeptidase inhibitor 2) and decreased NDUFS4 (NADH dehydrogenase
      (ubiquinone) Fe-S protein4), VEGFA (vascular endothelial growth factor A), and
      DDIT3 (DNA-damage-inducible transcript 3) which associated cell migration and
      invasion in B16F10 cells. Based on those observations, we suggest that casticin
      could be used as a novel anticancer metastasis of melanoma cancer in the future.

PMID- 28444821
TI  - Has the autonomy pendulum swung too far?
AB  - BACKGROUND: This paper aims to contribute to the discussion about patient-centred
      care in surgery. It is contended here that the paradigm shift towards patient
      centred decision-making in health care does not mean that patient values alone
      (or those of their proxies) should, uncritically, be the lead decision makers in
      determining surgical care. METHODS: In support of that contention, three
      clarifications to our conception of autonomy will be offered. RESULTS: First,
      autonomy may not be best positioned as the lead principle guiding healthcare
      decision-making. Second, arguably, our traditional understanding of autonomy, as
      it might be applied to health care, is incomplete. Third, where autonomy is
      vested is contentious, and proxy decision makers can further complicate the
      decision-making process. CONCLUSION: It will be argued that an approach of
      inclusive, non-coercive and reflective dialogue seeking a consensual decision
      amongst all those affected is more appropriate for moral decision-making in
      surgery. This dialogue is set in the actual reality of the patient's illness.
      During the discourse, each participant has equal rights to contribute and to be
      heard, equal duties not to coerce and equal co-responsibilities to share the
      perspectives of others in the discourse, with an aim to reach consensus.

PMID- 28444822
TI  - Triplex DNA Nanostructures: From Basic Properties to Applications.
AB  - Triplex nucleic acids have recently attracted interest as part of the rich
      "toolbox" of structures used to develop DNA-based nanostructures and materials.
      This Review addresses the use of DNA triplexes to assemble sensing platforms and
      molecular switches. Furthermore, the pH-induced, switchable assembly and
      dissociation of triplex-DNA-bridged nanostructures are presented. Specifically,
      the aggregation/deaggregation of nanoparticles, the reversible oligomerization of
      origami tiles and DNA circles, and the use of triplex DNA structures as
      functional units for the assembly of pH-responsive systems and materials are
      described. Examples include semiconductor-loaded DNA-stabilized microcapsules,
      DNA-functionalized dye-loaded metal-organic frameworks (MOFs), and the pH-induced
      release of the loads. Furthermore, the design of stimuli-responsive DNA-based
      hydrogels undergoing reversible pH-induced hydrogel-to-solution transitions using
      triplex nucleic acids is introduced, and the use of triplex DNA to assemble shape
      memory hydrogels is discussed. An outlook for possible future applications of
      triplex nucleic acids is also provided.

PMID- 28444823
TI  - Dissociable corticostriatal circuits underlie goal-directed vs. cue-elicited
      habitual food seeking after satiation: evidence from a multimodal MRI study.
AB  - The present multimodal MRI study advances our understanding of the
      corticostriatal circuits underlying goal-directed vs. cue-driven, habitual food
      seeking. To this end, we employed a computerized Pavlovian-instrumental transfer
      paradigm. During the test phase, participants were free to perform learned
      instrumental responses (left and right key presses) for popcorn and Smarties
      outcomes. Importantly, prior to this test half of the participants had been sated
      on popcorn and the other half on Smarties - resulting in a reduced desirability
      of those outcomes. Furthermore, during a proportion of the test trials, food
      associated Pavlovian cues were presented in the background. In line with previous
      studies, we found that participants were able to perform in a goal-directed
      manner in the absence of Pavlovian cues, meaning that specific satiation
      selectively reduced responding for that food. However, presentation of Pavlovian
      cues biased choice toward the associated food reward regardless of satiation.
      Functional MRI analyses revealed that, in the absence of Pavlovian cues,
      posterior ventromedial prefrontal cortex tracked outcome value. In contrast,
      during cued trials, the BOLD signal in the posterior putamen differentiated
      between responses compatible and incompatible with the cue-associated outcome.
      Furthermore, we identified a region in ventral amygdala showing relatively strong
      functional connectivity with posterior putamen during the cued trials. Structural
      MRI analyses provided converging evidence for the involvement of corticostriatal
      circuits: diffusion tensor imaging data revealed that connectivity of caudate
      seeded white-matter tracts to the ventromedial prefrontal cortex predicted
      responding for still-valuable outcomes; and gray matter integrity in the premotor
      cortex predicted individual Pavlovian cueing effects.

PMID- 28444824
TI  - A comparison between patients with epiphora and cataract of the activity
      limitations they experience in daily life due to their visual disability.
AB  - PURPOSE: The objective of this study was to compare patients with epiphora and
      cataract in terms of the activity limitations they experience in daily life due
      to their visual disability and to validate the use of the Catquest-9SF
      questionnaire for epiphora patients. METHODS: Seventy-two consecutively
      encountered adult patients with confirmed lacrimal obstruction and listed for
      dacryocystorhinostomy (DCR) or lacrimal intubation at the St. Erik Eye Hospital,
      Stockholm, Sweden, completed the Catquest-9SF questionnaire, which measures
      activity limitations in daily life due to visual disability. The psychometric
      qualities of the Catquest-9SF results obtained from this group of patients were
      evaluated by Rasch analysis. Rasch analysis was further employed to convert the
      ordinal raw data to a Rasch score for comparison with the preoperative scores of
      patients registered in the Swedish National Cataract Register (NCR) during March
      2013. RESULTS: The Catquest-9SF exhibited good psychometric qualities when
      investigating epiphora patients, with the exception of a misfit for Item 4, the
      item regarding facial recognition. On the Rasch scale (-5.43 = no activity
      limitations to +5.01 = severe activity limitations), the mean score for epiphora
      patients was -0.82 while for patients listed for 1st eye and 2nd eye cataract
      surgery it was -0.17 and -0.76, respectively. An equivalence test confirmed that
      the reported visual disability of epiphora patients was not significantly
      different from visual disability reported by patients waiting for 2nd eye
      cataract surgery. CONCLUSION: The Catquest-9SF is a valid measure of visual
      disability in patients with epiphora. Epiphora patients experience visual
      disability to the same degree as patients awaiting 2nd eye cataract surgery.

PMID- 28444825
TI  - 3 Tesla magnetic resonance imaging study of the normal canine femoral and sciatic
      nerves.
AB  - Understanding the normal course and optimizing visualization of the canine
      peripheral nerves of the lumbar plexus, in particular the sciatic and the femoral
      nerves, is essential when interpreting images of patients with suspected
      peripheral neuropathies such as inflammatory or neoplastic conditions. The
      purpose of this prospective, anatomic study was to describe the magnetic
      resonance imaging (MRI) anatomy of the normal canine femoral and sciatic nerves
      and to define the sequences in which the nerves are best depicted. A preliminary
      postmortem cadaver study was performed to determine optimal sequences and imaging
      protocol. In a second step the optimized technique was implemented on 10 healthy
      Beagle dogs, included in the study. The applied protocol included the following
      sequences: T1-weighted, T2-weighted, T2-Spectral Attenuated Inversion Recovery,
      T1-weighted postcontrast and T1-Spectral Presaturated Inversion Recovery
      postcontrast. All sequences had satisfactory signal-to-noise ratio and contrast
      resolution in all patients. The sciatic and femoral nerves were seen in all
      images. They were symmetric and of homogeneous signal intensity, being iso- to
      mildly hyperintense to muscle on T2-weighted, mildly hyperintense in T2-Spectral
      Attenuated Inversion Recovery, and iso- to mildly hypointense in T1-weighted
      images. No evidence of contrast enhancement in T1-weighted and T1-Spectral
      Presaturated Inversion Recovery postcontrast sequences was observed. The anatomic
      landmarks helpful to identify the course of the femoral and sciatic nerves are
      described in detail. This study may be used as an anatomical reference, depicting
      the normal canine femoral and sciatic nerves at 3 Tesla MRI.

PMID- 28444826
TI  - Indium(III)-catalyzed Aza-Conia-Ene Reaction for the Synthesis of Indolizines.
AB  - A new indium(III)-catalyzed reaction for the synthesis of a series of indolizine
      scaffolds has been developed. This methodology was highly efficient, allowing a
      low catalyst loading of 2 mol % (down to 0.5 mol %) and rendering the products in
      high yields through a 5-exo-dig aza-Conia-ene reaction. Furthermore, the
      possibility of incorporating an electrophile into the generated pyrrolidone ring
      in a one-pot synergistic fashion was demonstrated. Finally, based on experimental
      observations, a mechanism proposal was outlined.

PMID- 28444827
TI  - Fitness costs and life table parameters of highly insecticide-resistant strains
      of Plutella xylostella (L.) (Lepidoptera: Plutellidae) at different temperatures.
AB  - BACKGROUND: In many cases, resistance alleles have been associated with fitness
      costs and are often dependent on environmental factors such as temperature. Here,
      we studied the effects of temperature on the overall fitness, including
      development, survival and reproduction, of three insecticide-resistant and one
      susceptible strain of diamondback moth (DBM), Plutella xylostella (L.). RESULTS:
      The broader cross-resistance profile of the resistant strains previously selected
      by diamide and benzoylurea insecticides was tested. Cohort studies were conducted
      in the laboratory at three different temperatures (20 +/- 1  degrees C, 25 +/- 1 
      degrees C and 30 +/- 1  degrees C), and involved fitness costs were estimated. We
      observed significant differences in the development time, with the susceptible
      strain showing a shorter developmental period from egg stage to adult stage
      compared with the resistant strains. Moreover, the resistant strains differed
      significantly between one another. Additionally, the population growth parameters
      varied among the strains, with the benzoylurea-resistant strain showing the
      highest costs affecting the overall fitness of this strain. A temperature of 30 
      degrees C was unfavourable for DBM development, resulting in a reduced fitness in
      all strains. CONCLUSION: Benzoylurea selection pressure on a diamide-resistant P.
      xylostella strain resulted in lowest reproduction parameters and the longest
      generation time, as well as doubling the time among all strains tested. This
      suggests significant effects on the overall fitness and population growth
      parameters for diamide-resistant populations pressured by benzoylureas under
      applied conditions. (c) 2017 Society of Chemical Industry.

PMID- 28444828
TI  - Labeling and defining severe and enduring anorexia nervosa: A systematic review
      and critical analysis.
AB  - OBJECTIVE: With anorexia nervosa (AN) having various presentations, attention has
      been directed towards particularly durable forms of the condition in both
      research and clinical contexts. A major hindrance in terms of advancing the field
      is the inconsistent labeling and defining of this subgroup. This has two
      implications; first, the inconsistent recruitment of participants when
      researching this sample, and second, the misdiagnosing of patients who may or may
      not have a durable course of the disease. The current research had the purpose of
      providing an overview of the current labels and criteria used for defining cases
      of severe and enduring AN, and critically analysing the implications of these
      findings. METHOD: In accordance with PRISMA guidelines, a literature search was
      conducted using four electronic databases (PsycINFO, MEDLINE, Web of Science and
      Scopus) in order to identify 32 records that met the standards stipulated by the
      criteria. Data extraction included explicit labeling, the definition or criteria
      used to describe the subgroup, along with participant age and study design.
      RESULTS: It was found that the terms chronic and severe and enduring were the
      most commonly used adjectives when referring to this subgroup. In terms of
      criteria, illness duration and the number of previously failed treatment attempts
      were the most common defining features within the literature. DISCUSSION: It is
      the aim of the authors to inspire further research into what is the most
      appropriate label and defining features for the subgroup in order to facilitate a
      better approach and outcome for the individuals affected.

PMID- 28444830
TI  - Gene expression reveals evidence for EGFR-dependent proximal-distal limb
      patterning in a myriapod.
AB  - Evolution of segmented limbs is one of the key innovations of Arthropoda,
      allowing development of functionally specific specialized head and trunk
      appendages, a major factor behind their unmatched evolutionary success.
      Proximodistal limb patterning is controlled by two regulatory networks in the
      vinegar fly Drosophila melanogaster, and other insects. The first is represented
      by the function of the morphogens Wingless (Wg) and Decapentaplegic (Dpp); the
      second by the EGFR-signaling cascade. While the role of Wg and Dpp has been
      studied in a wide range of arthropods representing all main branches, that is,
      Pancrustacea (= Hexapoda + Crustacea), Myriapoda and Chelicerata, investigation
      of the potential role of EGFR-signaling is restricted to insects (Hexapoda). Gene
      expression analysis of Egfr, its potential ligands, and putative downstream
      factors in the pill millipede Glomeris marginata (Myriapoda: Diplopoda), reveals
      that-in at least mandibulate arthropods-EGFR-signaling is likely a conserved
      regulatory mechanism in proximodistal limb patterning.

PMID- 28444829
TI  - Disparities in HIV-1 transmitted drug resistance detected by ultradeep sequencing
      between men who have sex with men and heterosexual populations.
AB  - OBJECTIVES: Transmitted drug resistance (TDR) can impair the response to first
      line antiretroviral therapy. In treatment-naive patients chronically infected
      with HIV type 1 (HIV-1), it was previously shown through Sanger sequencing that
      TDR was more common in men who have sex with men (MSM) than in other transmission
      risk groups. We aimed to compare two HIV-1 transmission groups in terms of the
      presence of TDR mutations. METHODS: We investigated, through Sanger sequencing
      and ultradeep sequencing (UDS), the presence of resistance mutations, both in
      majority (> 20%) and in minority (1-20%) proportions, in 70 treatment-naive MSM
      and 70 treatment-naive heterosexual patients who recently screened positive for
      HIV-1. RESULTS: The global prevalence of TDR was not significantly different
      between the two groups, either by Sanger or by UDS. Nevertheless, a higher
      frequency of nucleoside reverse transcriptase inhibitor TDR was observed among
      heterosexual patients (P = 0.04). There was also a trend for a higher frequency
      of TDR among MSM infected with HIV-1 subtype B compared with MSM infected with
      HIV-1 non-B subtypes (P = 0.06). CONCLUSIONS: Ultradeep sequencing UDS allowed
      sensitive monitoring of TDR, and highlighted some disparities between
      transmission groups.

PMID- 28444831
TI  - Analysis of modulation factor to shorten the delivery time in helical
      tomotherapy.
AB  - A low modulation factor (MF) maintaining a good dose distribution contributes to
      the shortening of the delivery time and efficiency of the treatment plan in
      helical tomotherapy. The purpose of this study was to reduce the delivery time
      using initial values and the upper limit values of MF. First, patients with head
      and neck cancer (293 cases) or prostate cancer (181 cases) treated between June
      2011 and July 2015 were included in the analysis of MF values. The initial MF
      value (MFinitial ) was defined as the average MFactual value, and the upper limit
      of the MF value (MFUL ) was defined according the following equation: MFUL = 2 *
      standard deviation of MFactual value + the average MFactual Next, a treatment
      plan was designed for patients with head and neck cancer (62 cases) and prostate
      cancer (13 cases) treated between December 2015 and June 2016. The average
      MFactual value for the nasopharynx, oropharynx, hypopharynx, and prostate cases
      decreased from 2.1 to 1.9 (p = 0.0006), 1.9 to 1.6 (p < 0.0001), 2.0 to 1.7 (p <
      0.0001), and 1.8 to 1.6 (p = 0.0004) by adapting the MFinitial and the MFUL
      values, respectively. The average delivery time for the nasopharynx, oropharynx,
      hypopharynx, and prostate cases also decreased from 19.9 s cm-1 to 16.7 s cm-1 (p
      < 0.0001), 15.0 s cm-1 to 13.9 s cm-1 (p = 0.025), 15.1 s cm-1 to 13.8 s cm-1 (p
      = 0.015), and 23.6 s cm-1 to 16.9 s cm-1 (p = 0.008) respectively. The delivery
      time was shortened by the adaptation of MFinitial and MFUL values with a
      reduction in the average MFactual for head and neck cancer and prostate cancer
      cases.

PMID- 28444832
TI  - Real-time activation of central cholinergic circuits during recognition memory.
AB  - Short latency afferent inhibition (SAI) is a paired-pulse transcranial magnetic
      stimulation (TMS) protocol that consists in the inhibition of the motor evoked
      potentials (MEPs) by afferent sensory impulses. SAI is thought to be mediated by
      cholinergic projections over M1 and can be considered a putative marker of
      central cholinergic activity. It is known that memory processes are regulated by
      acetylcholine. Nonetheless, the influence of memory tasks on SAI has not been
      investigated. Here we tested changes in SAI circuits in healthy subjects
      performing a computerized non-verbal recognition memory task (RMT) requiring to
      recognize previously encoded faces. SAI protocol was recorded during five phases
      of the RMT: baseline, encoding, consolidation, retrieval, and post-task. In the
      control task, subjects were asked to judge a visual feature of not previously
      presented faces. SAI protocol was applied over the same conditions as in the RMT.
      We found that SAI remarkably increases during the retrieval phase of the RMT as
      compared to baseline. On the other hand no change was observed during the control
      task. These findings show that SAI can be modulated by ongoing memory processes
      and support the hypothesis that SAI can be considered as a neurophysiological
      marker of central cholinergic activity.

PMID- 28444833
TI  - Chronic stress-induced mechanical hyperalgesia is controlled by capsaicin
      sensitive neurones in the mouse.
AB  - BACKGROUND: Clinical studies demonstrated peripheral nociceptor deficit in stress
      related chronic pain states, such as fibromyalgia. The interactions of stress and
      nociceptive systems have special relevance in chronic pain, but the underlying
      mechanisms including the role of specific nociceptor populations remain unknown.
      We investigated the role of capsaicin-sensitive neurones in chronic stress
      related nociceptive changes. METHOD: Capsaicin-sensitive neurones were
      desensitized by the capsaicin analogue resiniferatoxin (RTX) in CD1 mice. The
      effects of desensitization on chronic restraint stress (CRS)-induced responses
      were analysed using behavioural tests, chronic neuronal activity assessment in
      the central nervous system with FosB immunohistochemistry and peripheral cytokine
      concentration measurements. RESULTS: Chronic restraint stress induced mechanical
      and cold hypersensitivity and increased light preference in the light-dark box
      test. Open-field and tail suspension test activities were not altered. Adrenal
      weight increased, whereas thymus and body weights decreased in response to CRS.
      FosB immunopositivity increased in the insular cortex, dorsomedial hypothalamic
      and dorsal raphe nuclei, but not in the spinal cord dorsal horn after the CRS.
      CRS did not affect the cytokine concentrations of hindpaw tissues. Surprisingly,
      RTX pretreatment augmented stress-induced mechanical hyperalgesia, abolished
      light preference and selectively decreased the CRS-induced neuronal activation in
      the insular cortex. RTX pretreatment alone increased the basal noxious heat
      threshold without influencing the CRS-evoked cold hyperalgesia and augmented
      neuronal activation in the somatosensory cortex and interleukin-1alpha and RANTES
      production. CONCLUSIONS: Chronic restraint stress induces hyperalgesia without
      major anxiety, depression-like behaviour or peripheral inflammatory changes.
      Increased stress-induced mechanical hypersensitivity in RTX-pretreated mice is
      presumably mediated by central mechanisms including cortical plastic changes.
      SIGNIFICANCE: These are the first data demonstrating the complex interactions
      between capsaicin-sensitive neurones and chronic stress and their impact on
      nociception. Capsaicin-sensitive neurones are protective against stress-induced
      mechanical hyperalgesia by influencing neuronal plasticity in the brain.

PMID- 28444834
TI  - Direct and indirect effects of attention and visual function on gait impairment
      in Parkinson's disease: influence of task and turning.
AB  - Gait impairment is a core feature of Parkinson's disease (PD) which has been
      linked to cognitive and visual deficits, but interactions between these features
      are poorly understood. Monitoring saccades allows investigation of real-time
      cognitive and visual processes and their impact on gait when walking. This study
      explored: (i) saccade frequency when walking under different attentional
      manipulations of turning and dual-task; and (ii) direct and indirect
      relationships between saccades, gait impairment, vision and attention. Saccade
      frequency (number of fast eye movements per-second) was measured during gait in
      60 PD and 40 age-matched control participants using a mobile eye-tracker. Saccade
      frequency was significantly reduced in PD compared to controls during all
      conditions. However, saccade frequency increased with a turn and decreased under
      dual-task for both groups. Poorer attention directly related to saccade
      frequency, visual function and gait impairment in PD, but not controls. Saccade
      frequency did not directly relate to gait in PD, but did in controls. Instead,
      saccade frequency and visual function deficit indirectly impacted gait impairment
      in PD, which was underpinned by their relationship with attention. In conclusion,
      our results suggest a vital role for attention with direct and indirect
      influences on gait impairment in PD. Attention directly impacted saccade
      frequency, visual function and gait impairment in PD, with connotations for
      falls. It also underpinned indirect impact of visual and saccadic impairment on
      gait. Attention therefore represents a key therapeutic target that should be
      considered in future research.

PMID- 28444835
TI  - Cytomegalovirus infection- and dasatinib-induced proteinuria in Ph+ALL.

PMID- 28444836
TI  - Ephedra alkaloid contents of Chinese herbal formulae sold in Taiwan.
AB  - Consumption of Ephedra alkaloids is prohibited in-competition by the World Anti
      Doping Agency (WADA). In Taiwan, colds are often treated with Chinese herbal
      formulae containing Herba Ephedrae. We screened products sold in Taiwan and
      preliminarily assessed their relationships with WADA threshold violations. Fifty
      six concentrated powder products, including 19 Chinese herbal formulae that
      contained Herba Ephedrae, were collected. The content of Ephedra alkaloids,
      namely ephedrine (E), methylephedrine (ME), norpseudoephedrine (NPE; cathine),
      pseudoephedrine (PE), and norephedrine (NE; phenylpropanolamine), was determined
      using a validated high-performance liquid chromatography method. The results
      revealed that the phenotypic indicators of the collected products, E/PE and
      E/total ratios, were 1.52-4.70 and 0.49-0.72, respectively, indicating that the
      Herba Ephedrae species in these products was probably E. sinica or E. equisetina,
      but not E. intermedia. The contents of E, ME, NPE, PE, and NE and the total
      alkaloid contents in the daily doses of the products were 0.45-34.97, 0.05-4.87,
      0.04-3.61, 0.15-12.09, and 0.01-2.00 mg and 0.68-53.64 mg, respectively. The
      alkaloid contents followed a relatively consistent order (E > PE > ME ~ NPE >
      NE), even for products from different manufacturers. We calculated that single
      doses of 50.0% and 3.6% of the products would result in the WADA thresholds of E
      and NPE being exceeded, respectively. Our data provide critical information for
      athletes and medical personnel, who should be wary of using complex Chinese
      herbal formulae in addition to over-the-counter products.

PMID- 28444837
TI  - Prevalence and risk factors for diabetic retinopathy in 17 152 patients from the
      island of Funen, Denmark.
AB  - PURPOSE: This study aims to estimate the prevalence and risk factors of diabetic
      retinopathy (DR) in patients enrolled in a large Danish quality-assuring database
      for diabetes: the Funen Diabetes Database (FDDB). METHODS: All patients with type
      1 (T1DM) and type 2 DM (T2DM) diabetes mellitus (DM) were included in a cross
      sectional study. The level of DR per patient was determined based on the eye with
      highest level of DR. All ocular and non-ocular data were extracted at the latest
      examination that corresponded to the most recent DR-grading data. RESULTS: Data
      from 17 152 patients were analysed; 83.1% had T2DM. Prevalence of DR was 23.8%
      (T1DM: 54.3%, T2DM: 21.2%). T1/T2DM patients were statistically significantly
      different regarding age, duration of diabetes, BMI, systolic blood pressure (BP),
      cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, s-creatinine and u
      albumin (p < 0.001 for all). Increasing level of DR showed statistically
      significant association with age, duration of diabetes, systolic BP, HbA1c, s
      creatinine and u-albumine with increasing level of DR (all are p < 0.001) both
      T1DM/T2DM patients. CONCLUSION: The patients in FDDB had good systemic control
      with median values of BP, serum lipids, cholesterol and HbA1c all close to or
      below national guidelines at the time of data extraction, but still a high level
      of DR was found in this cohort. DR was more common in patients with T1DM than
      T2DM, but as T2DM patients are more numerous, their level of DR despite
      acceptable control is still concerning. Most important associated factors for
      higher levels of DR were age, duration of diabetes, HbA1c, s-creatinine and u
      albumine.

PMID- 28444838
TI  - Modified brow suspension technique for the treatment of pseudoptosis due to
      redundant frontal skin in the dog: a retrospective study of 25 cases.
AB  - PURPOSE: To describe the outcome of modified brow suspension technique for the
      treatment of upper eyelid pseudoptosis in canine patients with redundant frontal
      skin folds. METHODS: Medical records from 1999 to 2015 were retrospectively
      reviewed. Only dogs that underwent modified brow suspension for treating
      bilateral pseudoptosis were included in the study. Recorded data included breed,
      age, gender, main ophthalmic complaint, ocular findings, suture material used for
      brow suspension, number of slings placed, postoperative treatment, complications,
      follow-up time, and outcome. RESULTS: Twenty-five adult dogs of different gender
      and breed fulfilled the inclusion criteria, with the Shar-Pei being
      overrepresented (19/25;76%). The main complaint at first presentation was
      mucopurulent discharge (10/25;40%) and blepharospasm (10/25;40%). Concurrent
      corneal disease was diagnosed in 47 eyes (47/50;94%). Monofilament polyamide was
      the most frequently used suture material (46/50;92%). Number of slings placed
      varied, with one in two eyes (4%), two in 28 eyes (56%), three in 17 eyes (34%),
      and four in three eyes (6%). Complications were seen in three eyes (6%): suture
      rupture (one eye; 2%) and skin abscess (two eyes; 4%). Mean follow-up time was
      17.6 months (1-84 months), with no cases of fold dermatitis or dermatologic
      disease observed within this period. Good esthetic and functional outcomes were
      obtained in 47 eyes at first intervention (97%) and in all patients after re
      intervention. CONCLUSIONS: The modified brow suspension technique described
      offers a surgical alternative for dogs with pseudoptosis secondary to redundant
      frontal skin folds that potentially reduces anesthetic time and facial changes.

PMID- 28444840
TI  - TOPAS Simulation of the Mevion S250 compact proton therapy unit.
AB  - As proton therapy becomes increasingly popular, so does the need for Monte Carlo
      simulation studies involving accurate beam line modeling of proton treatment
      units. In this study, the 24 beam configurations of the Mevion S250 proton
      therapy system installed recently at our institution were modeled using the
      TOolkit for PArticle Simulation (TOPAS) code. Pristine Bragg peak, spread out
      Bragg peak (SOBP), and lateral beam profile dose distributions were simulated and
      matched to the measurements taken during commissioning of the unit. Differences
      in the range for all Percent Depth Dose (PDD) curves between measured and
      simulated data agreed to within 0.1 cm. For SOBP scans, the SOBP widths all
      agreed to within 0.3 cm. With regards to lateral beam profile comparisons between
      the measured and simulated data, the penumbras differed by less than 1 mm and the
      flatness differed by less than 1% in nearly all cases. This study shows that
      Monte Carlo simulation studies involving the Mevion S250 proton therapy unit can
      be a viable tool in commissioning and verification of the proton treatment
      planning system.

PMID- 28444839
TI  - Age-dependent alterations in osteoblast and osteoclast activity in human
      cancellous bone.
AB  - It is assumed that the activity of osteoblasts and osteoclasts is decreased in
      bone tissue of aged individuals. However, detailed investigation of the molecular
      signature of human bone from young compared to aged individuals confirming this
      assumption is lacking. In this study, quantitative expression analysis of genes
      related to osteogenesis and osteoclastogenesis of human cancellous bone derived
      from the distal radius of young and aged individuals was performed. Furthermore,
      we additionally performed immunohistochemical stainings. The young group included
      24 individuals with an average age of 23.2 years, which was compared to
      cancellous bone derived from 11 body donators with an average age of 81.0 years.
      In cancellous bone of young individuals, the osteogenesis-related genes RUNX-2,
      OSTERIX, OSTEOPONTIN and OSTEOCALCIN were significantly up-regulated compared to
      aged individuals. In addition, RANKL and NFATc1, both markers for
      osteoclastogenesis, were significantly induced in cancellous bone of young
      individuals, as well as the WNT gene family member WNT5a and the matrix
      metalloproteinases MMP-9. However, quantitative RT-PCR analysis of BMP-2, ALP,
      FGF-2, CYCLIN-D1, MMP-13, RANK, OSTEOPROTEGERIN and TGFb1 revealed no significant
      difference. Furthermore, Tartrate-resistant acid phosphatase (TRAP) staining was
      performed which indicated an increased osteoclast activity in cancellous bone of
      young individuals. In addition, pentachrome stainings revealed significantly less
      mineralized bone matrix, more osteoid and an increased bone density in young
      individuals. In summary, markers related to osteogenesis as well as
      osteoclastogenesis were significantly decreased in the aged individuals. Thus,
      the present data extends the knowledge about reduced bone regeneration and
      healing capacity observed in aged individuals.

PMID- 28444841
TI  - The effect of grapeseed oil on performance, rumen fermentation, antioxidant
      status and subcutaneous adipose fatty acid profile in lambs.
AB  - This experiment was carried out to examine the effect of grapeseed oil (GSO) on
      performance, rumen fermentation, antioxidant status and subcutaneous adipose
      fatty acid (FA) profile in lambs. Eighteen Baluchi lambs, 196 +/- 14 days of age
      and 39.8 +/- 1.7 kg body weight, were randomly assigned to three experimental
      diets: (i) diet without GSO (control), (ii) diet containing 2% of GSO (GSO2) and
      (iii) diet containing 4% of GSO (GSO4) for 42 days. Results showed that the
      experimental diets had no significant effect on dry matter intake and performance
      (p > 0.05). The supplemented diets with GSO had no effect on pH and NH3 -N of
      rumen fluid (p > 0.05), but GSO4 increased (p = 0.003) the concentration of
      propionic acid and reduced (p = 0.002) the concentration of acetate acid compared
      to the control. Inclusion 4% of GSO to the diet increased total antioxidant
      activity and decreased malondialdehyde in serum and muscle (p < 0.001). The level
      of blood glutathione peroxidase in diets containing GSO was higher than control
      diet (p = 0.02), but diets had no effect on superoxide dismutase in blood and
      muscle tissues (p > 0.05). The concentration of vaccenic acid, rumenic acid and
      linoleic acid and thus polyunsaturated fatty acid in subcutaneous fat was
      affected by experimental diets (p < 0.001), as control had the lowest amount of
      these FAs and GSO4 had the highest amount of them. Therefore, it can be concluded
      that the use of GSO up to 4% improves the antioxidant status and adipose fatty
      acid profile in lambs without effects on performance.

PMID- 28444842
TI  - Microwave-assisted preparation of poly(ionic liquids)-modified polystyrene
      magnetic nanospheres for phthalate esters extraction from beverages.
AB  - The fabrication of novel poly(ionic liquids)-modified polystyrene (PSt) magnetic
      nanospheres (PILs-PMNPs) by a one-pot miniemulsion copolymerization reaction was
      achieved through an efficient microwave-assisted synthesis method. The
      morphology, structure, and magnetic behavior of the as-prepared magnetic
      materials were characterized by using transmission electron microscopy, vibrating
      sample magnetometry, etc. The magnetic materials were utilized as sorbents for
      the extraction of phthalate esters (PAEs) from beverage samples followed by high
      performance ultrafast liquid chromatography analysis. Significant extraction
      parameters that could affect the extraction efficiencies were investigated
      particularly. Under optimum conditions, good linearity was obtained in the
      concentration range of 0.5-50 (dimethyl phthalate), 0.3-50 (diethyl phthalate),
      0.2-50 (butyl benzyl phthalate), and 0.4-50 MUg/L (di-n-butyl phthalate), with
      correlation coefficients R2  > 0.9989. Limits of detection were in the range 125
      350 pg. The proposed method was successfully applied to determine PAEs from
      beverage samples with satisfactory recovery ranging from 77.8 to 102.1% and
      relative standard deviations ranging from 3.7 to 8.4%. Comparisons of extraction
      efficiency with PSt-modified MNPs as sorbents were performed. The results
      demonstrated that PILs-PMNPs possessed an excellent adsorption capability toward
      the trace PAE analytes.

PMID- 28444843
TI  - Evaluation of two automated cell counters for the analysis of hematopoietic
      progenitor cell apheresis products.
AB  - INTRODUCTION: Routine hematology parameters in hematopoietic progenitor cell
      apheresis products (HPC-A) are usually determined using automated cell counters.
      These instruments, however, are designed to analyze whole blood samples, that
      differ considerably from HPC-A in blood cell composition. This study evaluates
      the performance of two automated cell counters for the analysis of HPC-A.
      METHODS: Routine hematology parameters [red blood cells (RBC), hematocrit (HCT),
      mean corpuscular volume (MCV), white blood cells (WBC), WBC differentiation, and
      platelets (PLT)] were determined on the Unicel DxH 800 instrument (Beckman
      Coulter) and the XN-350 instrument (Sysmex). Correlations with the reference
      methods, intrarun precision, and linearity of the analyses were studied. RESULTS:
      Good correlations were found for almost all parameters. However, RBC count was
      overestimated by XN-350, using the impedance technique, as was neutrophil
      percentage using DxH 800. Coefficients of variation for intrarun precision were
      below 10% on both analyzers for all parameters, except for neutrophil percentage
      (14.7%) and PLT (10%) on DxH 800. Both instruments showed good linearity for all
      parameters, except for RBC and HCT on DxH 800. CONCLUSION: With the exception of
      the measurement of neutrophils on DxH 800 and RBC by the impedance technique on
      the XN-350, routine hematology parameters in HPC-A can safely be determined using
      automated cell counters.

PMID- 28444844
TI  - Iranian clinical trials: An analysis of registered trials in International
      Clinical Trial Registry Platform (ICTRP).
AB  - OBJECTIVE: This study investigated and analyzed Iranian clinical trials
      registered in the ICTRP portal by the end of 2015. The goal was to determine
      which diseases are currently being studied and whether these are diseases that
      carry the greatest burden of disease according to regional and WHO statistics.
      MATERIALS AND METHODS: Information on clinical trials carried out in Iran was
      downloaded from the portal of the International Clinical Trials Registry website.
      By the end of 2015, 10,341 studies were registered from Iran. After removing
      duplicate and observational studies, 10,211 studies remained for analysis. The
      2016 edition of the International Classification of Diseases was used to classify
      the diseases. RESULTS: The frequency of studies was found to be mental and
      behavioral disorders (10.44%), diseases of the genitourinary system (10.2%), and
      endocrine, nutritional, and metabolic diseases (10.01%). Gastrointestinal and
      dermatologic diseases made up more than 12% of studies, but bear only 0.84% of
      the burden of disease in Iran. CONCLUSION: The results showed that, despite an
      increase in registration of clinical trials in Iran, most studies registered were
      conducted on diseases, which form only a small percentage of the total disease
      burden of the country.

PMID- 28444845
TI  - Predictors of complication following lower extremity amputation in diabetic end
      stage renal disease.
AB  - AIM: Patients with diabetic end-stage renal disease (ESRD) are at increased risk
      of lower extremity amputation (LEA) and postoperative complications compared to
      those without diabetic ESRD. This study sought to determine the factors that
      influence complications following LEA in patients with diabetic ESRD. METHODS: A
      total of 41 patients with diabetic ESRD (total of 46 amputations) who underwent
      LEA were enrolled in this study. The electronic medical records were
      retrospectively reviewed to identify the predictors of postoperative
      complications. The outcomes were divided into three categories: no complications,
      minor complications (wounds requiring only local care or oral antibiotics), and
      major complications (requiring surgical intervention, further amputations, or
      inducing life-threatening morbidities and mortalities). RESULTS: Multivariate
      logistic regression analysis demonstrated that underlying sepsis (P = 0.007) was
      the only significant risk factor for major complications, with an odds ratio
      demonstrating an 8.16 times increased risk of requiring another surgery or
      mortality compared to those without sepsis. CONCLUSION: Preoperative sepsis is an
      independent risk factor for major complications after LEA in patients with
      diabetic ESRD. We advise particular caution when performing LEA in diabetic ESRD
      patients who are also septic. Early amputation, prior to the development of
      sepsis, is preferable.

PMID- 28444846
TI  - Forensic analysis of latent fingermarks by silver-assisted LDI imaging MS on
      nonconductive surfaces.
AB  - Silver-assisted laser desorption ionization (AgLDI) imaging mass spectrometry
      (IMS) has been demonstrated to be a useful technology for fingermark analysis
      allowing for the detection of several classes of endogenous as well as exogenous
      compounds. Ideally, in IMS analyses, the fingermarks are deposited under
      controlled conditions on metallized conductive target slides. However, in
      forensic investigations, fingermarks are often found on a variety of
      nonconductive surfaces. A sputtered silver layer renders the target surface
      conductive, which allows the analyses of insulating surfaces by time-of-flight
      IMS. Ultimately, the major consideration when developing analytical methods for
      the analysis of latent fingermarks is their capability to be incorporated within
      forensic standard operational procedures. To demonstrate the potential of AgLDI
      IMS for forensic applications, fingermarks deposited on nonconductive surfaces
      commonly found during an investigation, including paper, cardboard, plastic bags
      and lifting tape, were first revealed by the Surete du Quebec by using forensic
      enhancement techniques prior to the IMS analyses. Numerous endogenous compounds
      including fatty acids, cholesterol, squalene, wax esters, triglycerides and
      several exogenous substances were detected and imaged. Here, we show that silver
      sputtering can provide visual enhancements of fingerprint patterns after FET
      procedures through different scenarios in which AgLDI IMS can contribute to
      forensic investigations. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444847
TI  - Complement Dependence of Murine Costimulatory Blockade-Resistant Cellular Cardiac
      Allograft Rejection.
AB  - Building on studies showing that ischemia-reperfusion-(I/R)-injury is complement
      dependent, we tested links among complement activation, transplantation
      associated I/R injury, and murine cardiac allograft rejection. We transplanted
      BALB/c hearts subjected to 8-h cold ischemic storage (CIS) into cytotoxic T
      lymphocyte associated protein 4 (CTLA4)Ig-treated wild-type (WT) or c3-/- B6
      recipients. Whereas allografts subjected to 8-h CIS rejected in WT recipients
      with a median survival time (MST) of 37 days, identically treated hearts survived
      >60 days in c3-/- mice (p < 0.05, n = 4-6/group). Mechanistic studies showed
      recipient C3 deficiency prevented induction of intragraft and serum
      chemokines/cytokines and blunted the priming, expansion, and graft infiltration
      of interferon-gamma-producing, donor-reactive T cells. MST of hearts subjected to
      8-h CIS was >60 days in mannose binding lectin (mbl1-/- mbl2-/- ) recipients and
      42 days in factor B (cfb-/- ) recipients (n = 4-6/group, p < 0.05, mbl1-/- mbl2-/
      vs. cfb-/- ), implicating the MBL (not alternative) pathway. To
      pharmacologically target MBL-initiated complement activation, we transplanted
      BALB/c hearts subjected to 8-h CIS into CTLA4Ig-treated WT B6 recipients with or
      without C1 inhibitor (C1-INH). Remarkably, peritransplantation administration of
      C1-INH prolonged graft survival (MST >60 days, p < 0.05 vs. controls, n = 6) and
      prevented CI-induced increases in donor-reactive, IFNgamma-producing spleen cells
      (p < 0.05). These new findings link donor I/R injury to T cell-mediated rejection
      through MBL-initiated, complement activation and support testing C1-INH
      administration to prevent CTLA4Ig-resistant rejection of deceased donor
      allografts in human transplant patients.

PMID- 28444848
TI  - Biologically meaningful scents: a framework for understanding predator-prey
      research across disciplines.
AB  - Fear of predation is a universal motivator. Because predators hunt using stealth
      and surprise, there is a widespread ability among prey to assess risk from
      chemical information - scents - in their environment. Consequently, scents often
      act as particularly strong modulators of memory and emotions. Recent advances in
      ecological research and analytical technology are leading to novel ways to use
      this chemical information to create effective attractants, repellents and anti
      anxiolytic compounds for wildlife managers, conservation biologists and health
      practitioners. However, there is extensive variation in the design, results, and
      interpretation of studies of olfactory-based risk discrimination. To understand
      the highly variable literature in this area, we adopt a multi-disciplinary
      approach and synthesize the latest findings from neurobiology, chemical ecology,
      and ethology to propose a contemporary framework that accounts for such disparate
      factors as the time-limited stability of chemicals, highly canalized mechanisms
      that influence prey responses, and the context within which these scents are
      detected (e.g. availability of alternative resources, perceived shelter, and
      ambient physical parameters). This framework helps to account for the wide range
      of reported responses by prey to predator scents, and explains, paradoxically,
      how the same individual predator scent can be interpreted as either safe or
      dangerous to a prey animal depending on how, when and where the cue was
      deposited. We provide a hypothetical example to illustrate the most common
      factors that influence how a predator scent (from dingoes, Canis dingo) may both
      attract and repel the same target organism (kangaroos, Macropus spp.). This
      framework identifies the catalysts that enable dynamic scents, odours or odorants
      to be used as attractants as well as deterrents. Because effective scent tools
      often relate to traumatic memories (fear and/or anxiety) that cause future
      avoidance, this information may also guide the development of appeasement,
      enrichment and anti-anxiolytic compounds, and help explain the observed variation
      in post-traumatic-related behaviours (including post-traumatic stress disorder,
      PTSD) among diverse terrestrial taxa, including humans.

PMID- 28444849
TI  - Multivalent Peptide-Nanoparticle Conjugates for Influenza-Virus Inhibition.
AB  - To inhibit binding of the influenza A virus to the host cell glycocalyx, we
      generate multivalent peptide-polymer nanoparticles binding with nanomolar
      affinity to the virus via its spike protein hemagglutinin. The chosen dendritic
      polyglycerol scaffolds are highly biocompatible and well suited for a multivalent
      presentation. We could demonstrate in vitro that by increasing the size of the
      polymer scaffold and adjusting the peptide density, viral infection is
      drastically reduced. Such a peptide-polymer conjugate qualified also in an in
      vivo infection scenario. With this study we introduce the first non-carbohydrate
      based, covalently linked, multivalent virus inhibitor in the nano- to picomolar
      range by ensuring low peptide-ligand density on a larger dendritic scaffold.

PMID- 28444850
TI  - Emotion dysregulation in hypochondriasis and depression.
AB  - BACKGROUND: The aim of this study was to explore whether certain aspects of
      emotion dysregulation (i.e., facets of alexithymia and rumination) are more
      closely linked to hypochondriasis than to depression and vice versa. METHODS:
      Nineteen patients with hypochondriasis (HYP), 33 patients with depression, and 52
      healthy control participants completed the Toronto Alexithymia Scale, the
      Response Styles Questionnaire, and additional symptom and illness behaviour
      scales. A clinical interview was used to establish DSM-IV diagnoses and to
      exclude all cases with more than one axis I diagnosis. RESULTS: Depression
      patients reported more difficulties describing feelings and more symptom- and
      self-focused rumination than both HYP patients and healthy individuals, whereas
      HYP patients differed only from healthy individuals in regard to more
      difficulties in identifying feelings and more symptom-focused rumination.
      Multiple regression analyses, including all assessed facets of emotion
      dysregulation, showed that the degree of somatoform features (somatic symptoms,
      health anxiety, and illness behaviour) was specifically predicted by higher
      difficulties in identifying feelings scores, whereas depressive symptom levels
      were specifically predicted by higher rumination scores. CONCLUSIONS: Specific
      associations were found between difficulties in identifying feelings and key
      features of HYP, whereas depression was linked to a more generalized pattern of
      emotion regulation deficits. KEY PRACTITIONER MESSAGE: Emotion dysregulation can
      be found in hypochondriasis and depression Difficulties in identifying own
      feelings are specifically linked to somatic symptoms, health anxiety, and illness
      behaviour, whereas a more generalized pattern of emotion dysregulation is found
      in relation to depression Further research is needed to investigate whether the
      effectiveness of current treatments for depression, hypochondriasis, health
      anxiety, and related disorders could be improved by additional emotion regulation
      interventions.

PMID- 28444852
TI  - The renal elimination of apixaban: the totality of data relating to the renal
      clearance of apixaban in patients with impaired renal function: response to
      Hellfritzsch et al.

PMID- 28444853
TI  - Experimental type 2 diabetes induction reduces serum vaspin, but not serum
      omentin, in Wistar rats.
AB  - Vaspin and omentin are adipose tissue adipokines that have often been related to
      obesity and its comorbidities. The aim of this study was to investigate the
      behaviour of serum omentin and vaspin in models of type 2 diabetes. To do this,
      Wistar rats (~200 g) were randomly divided into two groups: a non-diabetic group
      (n = 6) and a diabetic group fed on a high-fat diet (n = 6) and a low dose of
      streptozotocin (Sigma(r) ). All procedures were approved by the Brazilian Ethics
      Committee. Body weight (BW) and food intake were recorded daily. Tail blood
      glucose levels were assessed at the end of the diabetes induction period. The
      insulin tolerance test (ITT) was performed after the diabetes induction period (7
      weeks). The serum and tissues (liver, pancreas, and retroperitoneal (RET),
      epididymal (EPI) and visceral (VIS) white adipose tissues) were immediately
      removed and weighed. Analyses of levels of insulin, omentin, vaspin, adiponectin
      and inflammatory cytokines IL-6, IL-8 (CXCL8), TNF-alpha and C-reactive protein
      (CRP) in serum were performed using the enzyme-linked immunosorbent assay
      (ELISA). Our results showed that IL-8 and CRP serum levels in the diabetic group
      were significantly higher than in the non-diabetic group. Vaspin and adiponectin
      values were lower for the diabetic group than for the non-diabetic group.
      Omentin, IL-6 and TNF-alpha values did not differ between the groups. Our results
      showed that both the metabolism of the adipose tissue and the secretion of
      adipokines may be affected in diabetic rats. Omentin showed no difference between
      the groups, although the vaspin values decreased in the diabetic group.

PMID- 28444854
TI  - Analysis of organic components in resin-modified pulp capping materials: critical
      considerations.
AB  - The purpose of this study was to elucidate the organic composition and eluates of
      three resin-based pulp-capping materials in relation to their indications and
      safety data sheets. Uncured samples of Theracal LC, Ultra-Blend Plus, and
      Calcimol LC were investigated using gas chromatography-mass spectrometry (GC-MS)
      and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).
      Identification/quantification of 7-d leachables of cured samples was performed
      using GC-MS for 2-hydroxyethyl methacrylate (HEMA), 2-(dimethylamino)ethyl
      methacrylate (DMAEMA), camphorquinone (CQ), ethylene glycol dimethacrylate
      (EGDMA), ethyl-4-(dimethylamino)benzoate (DMABEE), and triethylene glycol
      dimethacrylate (TEGDMA). A similar organic composition was found for Ultra-Blend
      and Calcimol; however, only Ultra-Blend is indicated for direct pulp-capping. In
      contrast to the other materials analysed, Theracal contained substances of high
      molecular weight. The safety data sheets of all materials were incomplete. We
      detected HEMA, CQ, and TEGDMA in eluates from Ultra-Blend and Calcimol, and it
      was considered that HEMA might have originated from decomposition of diurethane
      dimethacrylate (UDMA) in the GC-injector. For Theracal, additives associated with
      light curing (DMABEE and CQ) were detected in higher amounts (4.11 and 19.95 MUg
      mm-2 ) than in the other materials. Pores were quantified in all samples by micro
      computed tomography (micro-CT) analysis, which could influence leaching. The
      organic substances in the investigated materials might affect their clinical
      suitability as capping agents, especially for direct capping procedures.

PMID- 28444855
TI  - Intraguild interactions and behavior of Spodoptera frugiperda and Helicoverpa
      spp. on maize.
AB  - BACKGROUND: Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) is one of
      the major pests of maize and is in the same feeding guild as the noctuid pests
      Helicoverpa zea (Boddie) and Helicoverpa armigera (Hubner), recently reported in
      South and North America. The intraguild interactions of these species were
      assessed in laboratory and field conditions by determining the survival of larvae
      in interaction scenarios with non-Bt maize silks and ears. Moreover, a video
      tracking system was utilized to evaluate behavioral parameters during larval
      interactions in scenarios with or without food. RESULTS: In intraguild
      interactions, S. frugiperda had greater survival (55-100%) when competing with
      Helicoverpa spp. in scenarios where larvae were the same instar or when they were
      larger (fourth versus second) than their competitor. Frequency and time in food
      of S. frugiperda larvae were negatively influenced by interactions. Larvae of S.
      frugiperda moved shorter distances (less than 183.03 cm) compared with H. zea.
      CONCLUSION: Overall, S. frugiperda had a competitive advantage over Helicoverpa
      spp. This study provides significant information regarding noctuid behavior and
      larval survival during intraguild interactions, which may impact pest prevalence
      and population dynamics, thereby affecting integrated pest management and insect
      resistance management of these species in maize. (c) 2017 Society of Chemical
      Industry.

PMID- 28444856
TI  - Pharmacokinetics after a single dose of naloxone administered as a nasal spray in
      healthy volunteers.
AB  - BACKGROUND: There is increasing interest in the use of intranasal naloxone to
      reverse adverse opioid effects during management of procedural pain in children
      and in adults after overdose. There are limited data on the pharmacokinetics of
      intranasal naloxone so in this study we aimed to detail the pharmacokinetic
      profile of the commercially marketed injectable solution of naloxone 0.4 mg/ml
      when administered as an intranasal spray. METHODS: Twenty healthy volunteers
      received naloxone as an intranasal spray at a dose of 10 MUg/kg. Venous blood
      sampling was carried out for 90 min after administration to determine the time
      profile of the plasma concentrations of using tandem mass spectrometry.
      Pharmacokinetic parameters were calculated using a one-compartment model.
      RESULTS: Median time to maximum naloxone concentration (Tmax) was 14.5 (95% CI:
      9.0-16.5) min, mean maximum naloxone concentration (Cmax) was 1.09 +/- 0.56 ng/ml
      and mean AUC0-90 min was 37.1 +/- 15.0 ng*min/ml. Elimination half-life estimated
      from the median concentration data was 28.2 min. CONCLUSION: Our results show a
      faster uptake of intranasal naloxone to maximum concentration compared with
      previous studies although with a marked variation in maximum concentration. The
      findings are consistent with our clinical experience of the time profile for
      reversing the effects of sufentanil sedation in children.

PMID- 28444857
TI  - Strategies for removing a worn-out Bone-Anchored Hearing Aid abutment screw.

PMID- 28444858
TI  - Dietary protein content for an optimal diet: a clinical view.
AB  - The dietary protein role in different clinical nutritional conditions and some
      physio-pathological perspectives is a current and hot topic to discuss. Recent
      Proceedings of the Protein Summit 2, joining more than 60 nutrition scientists,
      health experts, and nutrition educators, suggest to increase plant but, in
      particular, animal protein intake because richer in leucine and consequently more
      effective to influence anabolic protein metabolism. The Panel conclusions are in
      apparent contradiction with the nutritional ecology statements, which strongly
      sustain the reduction of animal origin foods in the human diet and are currently
      concerned about the excessive, mainly animal protein intake in western and
      westernized Countries. In conclusion, it is time to carefully evaluate protein
      and aminoacid intake accurately considering quality, digestibility, daily
      distribution and individual characteristics.

PMID- 28444859
TI  - Roles of SAMHD1 in antiviral defense, autoimmunity and cancer.
AB  - The enzyme, sterile alpha motif and histidine-aspartic acid domain-containing
      protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type 1
      (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in
      myeloid cells and resting CD4+ T cells. This dNTP degradation reduces the dNTP
      concentration to a level insufficient for viral cDNA synthesis, thereby
      inhibiting retroviral replication. This antiviral enzymatic activity can be
      inhibited by viral protein X (Vpx). The HIV-2/SIV Vpx causes degradation of
      SAMHD1, thus interfering with the SAMHD1-mediated restriction of retroviral
      replication. Recently, SAMHD1 has been suggested to restrict HIV-1 infection by
      directly digesting genomic HIV-1 RNA through a still controversial RNase
      activity. Here, we summarize the current knowledge about structure, antiviral
      mechanisms, intracellular localization, interferon-regulated expression of
      SAMHD1. We also describe SAMHD1-deficient animal models and an antiviral drug on
      the basis of disrupting proteasomal degradation of SAMHD1. In addition, the
      possible roles of SAMHD1 in regulating innate immune sensing, Aicardi-Goutieres
      syndrome and cancer are discussed in this review.

PMID- 28444860
TI  - Aspirin responsiveness changes in obese patients following bariatric surgery.
AB  - AIMS: Bariatric surgery has emerged as a promising treatment option for weight
      loss and to counter the metabolic consequences of obesity. Obesity has been
      linked to a hyperaggregable state, as well as a blunted response to aspirin. This
      pilot study assessed the hypothesis that bariatric surgery would lead to an
      improvement in aspirin-induced platelet inhibition and a reduction in platelet
      aggregability. METHODS: Fifteen patients scheduled to undergo bariatric surgery
      were administered two 7-day courses of aspirin 81 mg: the first course
      administered before surgery and the second was 3 months following surgery.
      Platelet aggregation was measured before and after each aspirin course using
      VerifyNow-Aspirin. The primary endpoint was the change in on-treatment aspirin
      reactive units (ARU) pre- and postsurgery. Data from bariatric surgery study
      patients were compared to data of normal weighted subjects gathered in a previous
      study. RESULTS: Roux-en-Y gastric bypass was performed in 80%, and 20% underwent
      sleeve gastrectomy. The mean starting body mass index (BMI) was 46.9 kg/m2 .
      Patients lost on average 24.5 kg, resulting in a postsurgical BMI of 38.5 kg/m2 .
      Postbariatric surgery, off-treatment ARU was significantly reduced from
      presurgery levels (602+/-59 vs 531+/-78; P=.035). On-aspirin platelet reactivity
      was also significantly reduced following surgery (469+/-60 vs 432+/-143, P=.03).
      There was a significant correlation between the extent of weight loss and the
      degree of improvement in on-aspirin platelet reactivity (r2 =.49, P=.024).
      Presurgery on-aspirin platelet reactivity was significantly higher in obese
      patients compared to normal weighted subjects (469+/-60 vs 419+/-52; P=.016) and
      reduced to the baseline after the surgery (432+/-63 vs 419+/-52; P=.54).
      CONCLUSION: Aspirin-induced platelet inhibition may be more potent following
      bariatric surgery. The mechanisms behind this improvement require further
      investigation.

PMID- 28444862
TI  - Role of wireless motility capsule in the assessment and management of
      gastrointestinal dysmotility in patients with diabetes mellitus.
AB  - BACKGROUND: Gastrointestinal (GI) dysmotility is common in diabetic patients.
      Wireless Motility Capsule (WMC) provides the transit profile of the entire GI
      tract in a single study. Factors affecting GI dysmotility and utility of WMC
      study are not clearly established in diabetic patients. Our aims were to study
      the pattern of GI dysmotility using WMC and evaluate the effect of glycemic
      control and presence of diabetic microvascular complications on motility
      impairment in diabetic patients. We also assessed the impact of WMC findings on
      clinical management. METHODS: Retrospective chart review of all diabetic patients
      who underwent WMC testing at our institution from 2010 to 2015 was performed.
      Demographics, hemoglobinA1c levels, microvascular complications, and WMC findings
      were obtained. Impact of WMC on clinical management was assessed. KEY RESULTS: A
      total of 100 patients were included. Mean age was 45+/-19 years and 76% were
      female. Seventy-two percentage had abnormal WMC testing, of which 29 (40%) had
      multiregional dysmotility. There were no significant differences in demographics,
      diabetic microvascular complications or hemoglobinA1c levels among patients with
      normal and abnormal WMC testing or among patients with isolated vs multiregional
      dysmotility. Information about subsequent clinical management was available for
      47 patients. WMC testing was abnormal in 33 (70%) patients and treatment changes
      based on WMC results were made in 24 patients (73%). CONCLUSIONS & INFERENCES:
      There was no association between hemoglobinA1c levels, microvascular
      complications and pattern of GI dysmotility in diabetic patients undergoing WMC.
      WMC testing lead to management changes in approximately 75% of diabetic patients
      with GI dysmotility.

PMID- 28444861
TI  - LncRNA MALAT1 is dysregulated in diabetic nephropathy and involved in high
      glucose-induced podocyte injury via its interplay with beta-catenin.
AB  - Metastasis associated lung adenocarcinoma transcript 1(MALAT1) is a long non
      coding RNA, broadly expressed in mammalian tissues including kidney and up
      regulated in a variety of cancer cells. To date, its functions in podocytes are
      largely unknown. beta-catenin is a key mediator in the canonical and non
      canonical Wnt signalling pathway; its aberrant expression promotes podocyte
      malfunction and albuminuria, and contributes to kidney fibrosis. In this study,
      we found that MALAT1 levels were increased in kidney cortices from C57BL/6 mice
      with streptozocin (STZ)-induced diabetic nephropathy, and dynamically regulated
      in cultured mouse podocytes stimulated with high glucose, which showed a trend
      from rise to decline. The decline of MALAT1 levels was accompanied with beta
      catenin translocation to the nuclei and enhanced expression of serine/arginine
      splicing factor 1 (SRSF1), a MALAT1 RNA-binding protein. Further we showed early
      interference with MALAT1 siRNA partially restored podocytes function and
      prohibited beta-catenin nuclear accumulation and SRSF1 overexpression.
      Intriguingly, we showed that beta-catenin was involved in MALAT1 transcription by
      binding to the promotor region of MALAT1; beta-catenin knock-down also decreased
      MALAT1 levels, suggesting a novel feedback regulation between MALAT1 and beta
      catenin. Notably, beta-catenin deletion had limited effects on SRSF1 expression,
      demonstrating beta-catenin might serve as a downstream signal of SRSF1. These
      findings provided evidence for a pivotal role of MALAT1 in diabetic nephropathy
      and high glucose-induced podocyte damage.

PMID- 28444863
TI  - The prevalence of type 2 diabetes in urban Bo, Sierra Leone, and in the 16
      countries of the West Africa region.
AB  - BACKGROUND: The goal of this study was to measure the prevalence of diabetes
      among adults in urban Bo, Sierra Leone, and to compare the new results to the
      diabetes prevalence rates reported from studies across West Africa. METHODS: A
      total of 694 outpatients ages 18 and older at Bo Government Hospital were tested
      for diabetes between January 2012 and December 2014. Diabetes was defined as a
      fasting blood sugar level of >=126 mg/dL (>=7.0 mmol/L). RESULTS: The overall
      prevalence of diabetes was 6.2% (43/694). Diabetes prevalence increased from 0.8%
      (2/256) among patients ages 18 to 29 years to 3.9% (8/204) among patients ages 30
      to 39, 8.4% (11/131) among patients ages 40 to 49, 19.0% (12/63) among patients
      ages 50 to 59, and 25.0% (10/40) among patients ages 60 and older. The prevalence
      of diabetes was 5.2% among females and 7.4% among males. After adjusting the
      study population to the age and sex distribution of the national population, the
      standardized prevalence of diabetes was 7.0%. The only previously published study
      of diabetes in Sierra Leone found a much lower 2.4% prevalence rate in 1997. A
      comprehensive literature search identified studies from across West Africa
      (including Benin, Burkina Faso, Cabo Verde, Cote d'Ivoire, the Gambia, Ghana,
      Guinea, Guinea-Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra
      Leone, and Togo) that illustrate an increasing rate of diabetes and impaired
      glucose tolerance in the region. CONCLUSIONS: It is important for hospitals and
      clinics across West Africa to increase their ability to diagnose, monitor, and
      treat type 2 diabetes in urban and rural areas.

PMID- 28444864
TI  - Dose reduction and alternatives to the phenol pheromone in monitoring and
      management of the grass grub Costelytra zealandica.
AB  - BACKGROUND: Endemic New Zealand grass grub Costelytra zealandica is a pest of
      introduced pasture that uses phenol as a sex pheromone. The pheromone could be
      used to monitor and manage grass grub populations, but the irritating properties
      and toxicity of phenol for human handlers, as well as the possible
      ecotoxicological effects, pose obstacles to the deployment of the pheromone. This
      study aimed to limit the use of phenol by dose-response studies and investigation
      into alternative attractants and synergists to phenol. RESULTS: No difference in
      trap catch was seen across the range of 1-100 mg of phenol, while rates below
      this (0.001-0.1 mg) caused a large drop in catches. Our results indicated that 1
      mg loading in lures was enough to indicate beetle presence over 1 week. 4
      Hydroxybenzaldehyde and p-cresol proved unattractive in this study, both as
      single attractants and as synergists with phenol. Phenyl acetate, phenyl benzoate
      and diphenyl carbonate all formed phenol under hydrolytic conditions to act as
      successful propheromones, while phenyl acetate was found to be as attractive as
      phenol on its own. CONCLUSION: This study described several ways to reduce or
      avoid the use of phenol in the field while maintaining lure effectiveness. (c)
      2017 Society of Chemical Industry.

PMID- 28444865
TI  - A high rate of HIV-1 acquisition post immigration among migrants in Sweden
      determined by a CD4 T-cell decline trajectory model.
AB  - OBJECTIVES: There is a lack of knowledge about the extent to which migrants
      become HIV-1 infected after arrival in European countries. The objective of this
      study was to assess the extent to which migrants to Sweden become HIV-1 infected
      post immigration using a CD4 T-cell decline trajectory model. METHODS: All
      migrants (n = 2268) who were >= 15 years old, were diagnosed with HIV-1 infection
      in the period 1983-2013, had a known year of arrival in Sweden, did not have
      primary HIV infection and were not infected via mother-to-child transmission were
      included in the study. The CD4 T-cell decline trajectory model was applied and
      estimates of HIV acquisition were compared to the clinical reports. Phylogenetic
      analysis was performed in a subset of patients to explore whether this would
      favour the model or the doctor's estimate. RESULTS: The model estimated 19% of
      individuals to have been infected after arrival in Sweden, whereas the
      physician's estimate was 12%. In 79% of cases the estimates agreed. Discordance
      was predominantly seen when the doctor estimated HIV acquisition to have occurred
      before arrival in Sweden, while the model estimated it to have occurred after
      arrival in Sweden, and this type of discordance was seen in 10% of all patients.
      The probability of a discordance was greater for older patients, those with a
      high first CD4 T-cell count and those infected via heterosexual transmission. The
      phylogenetic analysis showed a higher concordance with the CD4 model than with
      the clinical reports (36 vs. 13%, respectively). CONCLUSIONS: The model indicated
      that a substantially higher proportion of migrants are infected after arrival in
      Sweden than estimated using clinical routine reports. It is therefore important
      to further emphasize primary preventive measures among migrants who have
      established themselves in their new country.

PMID- 28444866
TI  - New insights into neurogenic cyclic motor activity in the isolated guinea-pig
      colon.
AB  - BACKGROUND: The contents of the guinea pig distal colon consist of multiple
      pellets that move anally in a coordinated manner. This row of pellets results in
      continued distention of the colon. In this study, we have investigated
      quantitatively the features of the neurally dependent colonic motor patterns that
      are evoked by constant distension of the full length of guinea-pig colon.
      METHODS: Constant distension was applied to the excised guinea-pig by high
      resolution manometry catheters or by a series of hooks. KEY RESULTS: Constant
      distension elicited regular Cyclic Motor Complexes (CMCs) that originated at
      multiple different sites along the colon and propagated in an oral or anal
      direction extending distances of 18.3+/-10.3 cm. CMCs were blocked by
      tetrodotoxin (TTX; 0.6 MU mol L-1 ), hexamethonium (100 MU mol L-1 ) or hyoscine
      (1 MU mol L-1 ). Application of TTX in a localized compartment or cutting the gut
      circumferentially disrupted the spatial continuity of CMCs. Localized smooth
      muscle contraction was not required for CMC propagation. Shortening the length of
      the preparations or disruption of circumferential pathways reduced the integrity
      and continuity of CMCs. CONCLUSIONS & INFERENCES: CMCs are a distinctive neurally
      dependent cyclic motor pattern, that emerge with distension over long lengths of
      the distal colon. They do not require changes in muscle tension or contractility
      to entrain the neural activity underlying CMC propagation. CMCs are likely to
      play an important role interacting with the neuromechanical processes that time
      the propulsion of multiple natural pellets and may be particularly relevant in
      conditions of impaction or obstruction, where long segments of colon are
      simultaneously distended.

PMID- 28444867
TI  - Urine assay for tenofovir to monitor adherence in real time to tenofovir
      disoproxil fumarate/emtricitabine as pre-exposure prophylaxis.
AB  - OBJECTIVES: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is approved for
      pre-exposure prophylaxis (PrEP) against HIV infection. Adherence is critical for
      the success of PrEP, but current adherence measurements are inadequate for real
      time adherence monitoring. We developed and validated a urine assay to measure
      tenofovir (TFV) to objectively monitor adherence to PrEP. METHODS: We developed a
      urine assay using high-performance liquid chromatography coupled to tandem mass
      spectrometry with high sensitivity/specificity for TFV that allowed us to
      determine TFV concentrations in log10 categories between 0 and 10 000 ng/mL. We
      validated the assay in three cohorts: (1) HIV-positive subjects with undetectable
      viral loads on a TDF/FTC-based regimen, (2) healthy HIV-negative subjects who
      received a single dose of TDF/FTC, and (3) HIV-negative subjects receiving daily
      TDF/FTC as PrEP for 24 weeks. RESULTS: The urine assay detected TFV with greater
      sensitivity than plasma-based measures and with a window of measurements within 7
      days of the last TDF/FTC dose. Based on the urine log-linear clearance after the
      last dose and its concordance with all detectable plasma levels, a urine TFV
      concentration > 1000 ng/mL was identified as highly predictive of the presence of
      TFV in plasma at > 10 ng/mL. The urine assay was able to distinguish high and low
      adherence patterns within the last 48 h (> 1000 ng/mL versus 10-1000 ng/mL), as
      well as nonadherence (< 10 ng/mL) extended over at least 1 week prior to
      measurement. CONCLUSIONS: We provide proof of concept that a semiquantitative
      urine assay measuring levels of TFV could be further developed into a point-of
      care test and be a useful tool to monitor adherence to PrEP.

PMID- 28444868
TI  - An ecological approach to discover new bioactive extracts and products: the case
      of extremophile plants.
AB  - OBJECTIVES: Eight extremophile plants from Tunisia were screened to find natural
      products with benefits in human health. METHODS: These plants were collected in
      different areas in Tunisia. Their methanolic extracts were evaluated for their
      total phenolic content and for their antiradical (DPPH), antimicrobial (on 35
      bacteria and one yeast), antiviral (hepatitis C virus, HCV) and cytotoxic
      activity (against WI38 and J774 cell lines). The most active species were
      subjected to a bioguided fractionation. KEY FINDINGS: The screening revealed
      promising activity for four plants, but two species have both antiradical and
      antimicrobial activity: Juncus maritimus and Limonium virgatum. The rhizomes
      extract of J. maritimus showed the highest activity against HCV, a selective
      antibacterial activity against Streptococcus dysgalactiae, and a moderate
      antiradical activity which is due to luteolin isolated in one step by centrifugal
      partition chromatography. The stems' and leaves' extracts of L. virgatum were
      rich in polyphenols responsible for the antiradical activity. Also, Limonium
      extracts showed an antibacterial activity with a broad spectrum. CONCLUSIONS:
      Extremophile plants have proven to be a promising source for bioactive
      metabolites. They have a powerful antioxidant system highly influenced by biotic
      and abiotic factors and the ability to produce secondary metabolites with
      antimicrobial activity.

PMID- 28444869
TI  - Assessment of the usage of biodegradable polymeric matrix in vaginal devices to
      sustain progesterone release in cows.
AB  - The usage of timed artificial insemination (TAI) at a low cost leading to better
      reproductive rates has been the aim of several research groups in the field.
      Usually during TAI protocols, sustained progesterone (P4 ) release devices are
      employed. Most devices are constituted of a nylon skeleton covered with a silicon
      layer with P4 . A device based on biopolymers was developed in order to reduce
      costs and decrease its environmental impact. In this study, we compared the
      kinetics of sustained progesterone release among devices manufactured with a
      polymeric blend made of polyhydroxybutyrate-valerate (PHBV) and poly-epsilon
      caprolactone (PCL) (DISP) which were compared with DIB(r) (Internal Bovine
      Device) used as the control. In the in vitro and in vivo progesterone release
      tests, two types of biopolymer-based devices with a superficial area of 147 cm2
      were used: DISP8 (46% PHBV, 46% PCL and 8% P4 ; n = 4), DISP10 (45% PHBV, 45%
      PCL, 10% P4 ; n = 4) and DIB(r) (1 g P4 , 120 cm2 area; n = 3). The in vitro
      tests were carried out according to USP XXIII specifications and were performed
      in a dissolutor sink using an alcohol/water mixture (60/40 v/v) as a release
      media and samples were collected at 2 min, 2, 4, 8, 12, 24, 48, 60, 72, 84 and 96
      h. P4 concentrations were measured through spectrophotometry in a 244 nm long
      wave. Three to 3 comparisons of angular coefficients of the straight lines
      obtained by regression analysis of accumulated P4 concentrations as a function of
      square root of time were carried out. Furthermore, the diffusion coefficient
      values of P4 were also determined for DISP8 and DISP10. The results showed that
      the concentrations of P4 were higher in the DISP10 (774.63 +/- 45.26 MUg/cm2
      /t1/2 ) compared to DISP8 (566.17 +/- 3.68 MUg/cm2 /t1/2 ) (P < 0.05). However,
      both DISP10 and DISP8 P4 concentrations did not differ from DIB(r) (677.39 +/-
      16.13 MUg/cm2 /t1/2 ). For the analysis of released quantities per day of the in
      vitro test, four periods were considered: 0-24, 24-48, 48-72 and 72-96 h. In the
      first 24 h, DISP8 released significantly less P4 than DISP10 or DIB(r), which did
      not differ among them. Between 24 and 48 h, DISP10 released significantly more P4
      than DIB(r). DISP8 released an intermediate P4 amount and did not differ
      significantly from DIB(r) or DISP10. Between 48 and 72 h, P4 quantity released by
      DISP10 was significant higher (P < 0.01) than that of DIB(r) and DISP8, which did
      not differ among themselves. Between 72 and 96 h, DISP10 released significantly
      more P4 than DIB(r), and DISP8 released an intermediate amount which did not
      differ from DIB(r) or DISP10 (P < 0.01). There was interaction between treatment
      and time (P = 0.0024). The diffusion coefficient values were: 1.36 * 10-8 (cm2
      /s) for DISP10 and 1.12 * 10-8 (cm2 /s) for DISP8. For the in vivo test,
      ovariectomized crossbred cows received DIB(r) (n = 4) or DISP8 (n = 8) in an
      alternate design with a non-balanced sequence (cross-over) added of measures
      repeated in time referring to 16 days of blood samples collection. Samples were
      analyzed through radioimmunoassay in solid phase using the commercial kit of DPC
      (Diagnostics Products Corporation). Plasma concentrations of P4 peaked at 4 h
      after the placement of the device, this being the only time in which plasma P4
      concentrations differed between DIB(r) (11.45 +/- 1.96) compared with DISP8 (9.23
      +/- 1.15 ng/mL) (P = 0.027). On day 8, plasma P4 concentrations were similar for
      DIB(r) (2.44 +/- 0.09) and DISP8 (1.89 +/- 0.13 ng/mL) (P = 0.58) showing that
      both devices were able to keep P4 concentrations above 1 ng/mL in the plasma of
      the cow during the 16 day in vivo test. In conclusion, devices manufactured with
      the blend of PHBV/PCL biopolymers can sustain the release of P4 in a similar
      manner as silicon.

PMID- 28444870
TI  - The greenscape shapes surfing of resource waves in a large migratory herbivore.
AB  - The Green Wave Hypothesis posits that herbivore migration manifests in response
      to waves of spring green-up (i.e. green-wave surfing). Nonetheless, empirical
      support for the Green Wave Hypothesis is mixed, and a framework for understanding
      variation in surfing is lacking. In a population of migratory mule deer
      (Odocoileus hemionus), 31% surfed plant phenology in spring as well as a
      theoretically perfect surfer, and 98% surfed better than random. Green-wave
      surfing varied among individuals and was unrelated to age or energetic state.
      Instead, the greenscape, which we define as the order, rate and duration of green
      up along migratory routes, was the primary factor influencing surfing. Our
      results indicate that migratory routes are more than a link between seasonal
      ranges, and they provide an important, but often overlooked, foraging habitat. In
      addition, the spatiotemporal configuration of forage resources that propagate
      along migratory routes shape animal movement and presumably, energy gains during
      migration.

PMID- 28444872
TI  - Saving costs through a coordinated care model for patients with hepatocellular
      cancer.
AB  - BACKGROUND: In keeping with recent trends, patients with hepatocellular cancer
      have had their care managed by a dedicated Nurse Coordinator at our tertiary
      Australian hospital since 2010. To date, there are few data to justify the cost
      effectiveness of this approach. AIMS: To quantify the potential cost saved
      through the employment of a Nurse Coordinator in the management of patients with
      hepatocellular carcinoma at a single tertiary-level Australian hospital. METHODS:
      A retrospective audit of patients managed by the Nurse Coordinator between 2010
      and 2015 was conducted. Consensus reports from previous meetings were reviewed,
      and nurse-initiated radiological procedures and encounters were identified.
      Clinical activities were prospectively evaluated over a 1-month period in July
      August 2015. The equivalent annual number of outpatient medical encounters spared
      was calculated. Using the national average cost of each gastroenterology
      outpatient encounter, a total annual cost was determined and was compared against
      the cost of funding the position. RESULTS: The activity of the Nurse Coordinator
      resulted in an equivalent of at least 175 outpatient encounters being spared per
      year, with a minimum annual cost saving of $85 750. A total of 113 encounters
      resulted from the independent delivery and initiation of multidisciplinary team
      meeting plans; 10 were attributed to nurse-led patient education, and 52 were
      equated to weekly clinical activities. This represented a net annual saving of
      $17 050. CONCLUSION: The incorporation of the Nurse Coordinator in the care
      pathway of patients with hepatocellular cancer is associated with a reduction in
      medical outpatient load and, consequently, a significant annual cost saving.

PMID- 28444871
TI  - Dihydroberberine exhibits synergistic effects with sunitinib on NSCLC NCI-H460
      cells by repressing MAP kinase pathways and inflammatory mediators.
AB  - Highly effective and attenuated dose schedules are good regimens for drug
      research and development. Combination chemotherapy is a good strategy in cancer
      therapy. We evaluated the antitumour effects of dihydroberberine combined with
      sunitinib (DCS) on the human non-small cell lung cancer cell lines (NSCLC), A549,
      NCI-H460, and NCI-H1299 in vitro and in vivo. DCS showed synergic effects on NCI
      H460 cell proliferation, colony formation and transplantable tumour growth, which
      suggested dihydroberberine increases the sensitivity of lung carcinoma to
      sunitinib. Further studies indicated that DCS down-regulated phosphorylation of
      JNK, p38, and NF-kappaB in NCI-H460 cells and tumours and suppressed the IkappaB
      and COX-2 expression. In addition, DCS reduced the secretion of the pro
      inflammatory cytokine, interleukin-1 (IL-1), in tumours. Inhibition of p38
      activation by DCS was a likely contributing factor in IL-1 and COX-2 down
      regulation. Consistent with these results, a genomewide microarray analysis found
      that DCS induced the expression of cell cycle signal molecules that are known to
      be affected by JNK and p38. The change of cell cycle, in turn, led to down
      regulation of JNK and p38, and further reduced IL-1 secretion. Collectively,
      these findings highlight potential molecular mechanisms of DCS chemotherapeutic
      activity and suggest that DCS is an efficacious strategy in NSCLC therapy.

PMID- 28444873
TI  - Hematologic, hepatic, and renal function changes in hospitalized patients with
      Middle East respiratory syndrome coronavirus.
AB  - BACKGROUND: There are no longitudinal data on the changes in hematologic,
      hepatic, and renal function findings in patients with Middle East respiratory
      syndrome coronavirus (MERS-CoV) infection. METHODS: This is a retrospective
      cohort study of 16 MERS-CoV patients, to describe the hematological, hepatic, and
      renal findings of patients with MERS-CoV. RESULTS: During the 21 days of
      observation, there was no significant change in the hepatic panel or creatinine
      tests. There was a significant increase in the mean +/- SD of the white blood
      cell count from 8.3 +/- 4.6 to 14.53 +/- 7 (P value = 0.001) and an increase in
      mean +/- SD of the absolute neutrophil count from 6.33 +/- 4.2 to 12 +/- 5.5 (P
      value = 0.015). Leukocytosis was observed in 31% (5/16) of the patients on day 1
      and in 80% (4/5) on day 21. Transient leukopenia developed in 6% (1/16) of the
      patients on day 1 and in 13% (1/8) on day 8. None of the patients had
      neutropenia. Lymphopenia was a prominent feature with a rate of 44% (7/16) of the
      patients on day 1 and 60% (3/5) on day 21. Lymphocytosis was not a feature of
      MERS-CoV infection. Thrombocytopenia developed in 31% (5/16) of the patients on
      day 1 and 40% (2/5) on day 21. Thrombocytosis was not a prominent feature and was
      observed in 6% (1/16) of the patients on day 1 and 17% (1/6) on day 9.
      CONCLUSIONS: Patients with MERS-CoV infection showed variable hematologic
      parameters over time. Lymphocytosis and neutropenia were not features of MERS-CoV
      infection.

PMID- 28444874
TI  - Prognostic impact of chromosomal aberrations and GNAQ, GNA11 and BAP1 mutations
      in uveal melanoma.
AB  - PURPOSE: To evaluate clinico-pathological and molecular prognostic factors in a
      well-defined series of posterior uveal melanoma (UM) with focus on chromosomal
      aberrations and mutations in the GNAQ, GNA11 and BRCA1-associated protein 1
      (BAP1) genes. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue samples
      were obtained from 50 consecutive eyes enucleated for UM between 1993 and 2005.
      The material was tested for loss of chromosome 3 and gain of chromosome 8q gene
      signatures by selective molecular gene markers using multiplex ligation-dependent
      probe amplification (MLPA), and for DNA mutations in the GNAQ, GNA11 and BAP1
      genes. RESULTS: After a mean follow-up of 83 months (range, 8-205 months), 21
      patients had died of metastatic UM and 16 patients of other causes. Tumour
      diameter, ciliary body involvement, mixed/epithelioid cell types, mitotic index,
      Ki-67 proliferation index, loss of chromosome 3 and gain of chromosome 8q showed
      statistically significant associations with metastatic disease. There were no
      significant differences in the prevalence of GNAQ and GNA11 mutations between
      patients with or without metastatic disease. Mutational analysis of the BAP1 gene
      was performed in 32 primary UM and in five UM liver metastases. Nine different
      BAP1 missense mutations were identified. BAP1 mutations were not more common in
      metastasizing than in nonmetastasizing UM. CONCLUSION: The molecular gene markers
      showing loss of chromosome 3 and gain of 8q gene signatures were associated with
      an increased risk of metastatic disease. BRCA1-associated protein 1 (BAP1) gene
      mutation status had no prognostic significance. The frequency and spectrum of
      BAP1 mutations in UM may be more dependent on ethnicity and demographic variables
      than hitherto considered.

PMID- 28444875
TI  - Methylglyoxal-induced apoptosis is dependent on the suppression of c-FLIPL
      expression via down-regulation of p65 in endothelial cells.
AB  - Methylglyoxal (MGO) is a reactive dicarbonyl metabolite of glucose, and its
      plasma levels are elevated in patients with diabetes. Studies have shown that MGO
      combines with the amino and sulphhydryl groups of proteins to form stable
      advanced glycation end products (AGEs), which are associated with vascular
      endothelial cell (EC) injury and may contribute to the progression of
      atherosclerosis. In this study, MGO induced apoptosis in a dose-dependent manner
      in HUVECs, which was attenuated by pre-treatment with z-VAD, a pan caspase
      inhibitor. Treatment with MGO increased ROS levels, followed by dose-dependent
      down-regulation of c-FLIPL . In addition, pre-treatment with the ROS scavenger
      NAC prevented the MGO-induced down-regulation of p65 and c-FLIPL , and the forced
      expression of c-FLIPL attenuated MGO-mediated apoptosis. Furthermore, MGO-induced
      apoptotic cell death in endothelium isolated from mouse aortas. Finally, MGO was
      found to induce apoptosis by down-regulating p65 expression at both the
      transcriptional and posttranslational levels, and thus, to inhibit c-FLIPL mRNA
      expression by suppressing NF-kappaB transcriptional activity. Collectively, this
      study showed that MGO-induced apoptosis is dependent on c-FLIPL down-regulation
      via ROS-mediated down-regulation of p65 expression in endothelial cells.

PMID- 28444876
TI  - Cataracts in a population of Bengal cats in France.
AB  - OBJECTIVE: To document the clinical appearance and prevalence of cataracts in a
      French population of Bengal cats. METHODS: Two distinct populations of Bengal
      cats were examined as follows: (i) 51 animals recruited for evaluation of
      national prevalence of ocular diseases in an observational study conducted
      between October 2014 and November 2016 at the Alfort ophthalmology unit; (ii) 12
      patients referred for cataract diagnosis examined at a veterinary eye clinic
      located in central France, between December 2014 and February 2016. Buccal swabs
      or blood samples for DNA analysis were collected from all patients. The pedigrees
      of the examined Bengal cats were also investigated. RESULTS: Cataracts were
      diagnosed in 23 of 51 (45%) cats in the observational study and in all cats in
      the referral population, mostly bilaterally. Visual impairment was never
      reported. Age of subjects affected by cataracts ranged from 3 months to 9.6 years
      (median: 1.9 years). Cataracts were classified as nuclear cataracts (14 of 23 in
      the observational group and 12 of 12 in the referral group) with a focal,
      perinuclear, posterior, or complete nuclear pattern, or posterior polar
      subcapsular cataracts (10 of 23 only in the observational group). An inherited
      congenital origin appears to be the most likely hypothesis. The pedigree analysis
      suggests a hereditary component of cataract formation, but further analyses in a
      larger population or test matings are needed to determine the exact mode of
      inheritance. CONCLUSION: Presumed inherited cataracts appear to have a high
      prevalence in Bengal cats in France. The main manifestations are nuclear or
      subcapsular form, mostly bilateral, symmetrical, and apparently nonprogressive.

PMID- 28444877
TI  - Identification and measurement of staphylococcal enterotoxin M from
      Staphylococcus aureus isolate associated with staphylococcal food poisoning.
AB  - : Staphylococcus aureus produces a wide variety of staphylococcal enterotoxins
      (SEs, SEA to SEX), which are responsible for staphylococcal food poisoning. This
      study is aimed to establish a system to detect staphylococcal enterotoxin M (SEM)
      protein in food matrixes. In the present study, sem gene was characterized in a
      S. aureus isolate H4 associated with food poisoning. The amino acid sequence of
      the deduced SEM protein was same as that of previously identified SEM from S.
      aureus 04-02981. Subsequently, mature SEM protein was expressed in Escherichia
      coli BL21 (DE3) cells and purified with a Ni-NTA spin column. The polyclonal and
      monoclonal antibody against it were prepared. Using these antibodies, a highly
      sensitive, specific sandwich enzyme-linked immunosorbent assay (ELISA) system was
      developed capable of detecting SEM in milk, meat and rice. Cross-reactivity with
      SEB, SEI and SEK in this method was insignificant. Quantification of SEM
      secretion in vitro using this novel capture ELISA revealed that SEM was mainly
      secreted during the transition from the exponential to the stationary phase.
      Furthermore, sem gene and SEM protein production were screened by PCR and the
      developed ELISA system. The results indicated that there were two SEM+ strains of
      19 S. aureus isolates originating in cold dishes and humans suffering from food
      poisoning. The investigations make it possible to assess SEM in food hygiene
      supervision in near future. SIGNIFICANCE AND IMPACT OF THE STUDY: Staphylococcal
      enterotoxins (SE) are the main causative agents of staphylococcal food poisoning.
      Unlike classical SEs (SEA to SEE), the relationship between newly identified SEs
      (SEG to SEX) and staphylococcal food poisoning has not been clearly elucidated.
      Recently, mild emetic potential of staphylococcal enterotoxin M (SEM) has been
      demonstrated, which indicated that SEM might be associated with food poisoning.
      However, there is currently no commercial enzyme-linked immunosorbent assay
      (ELISA) kit available for immunological detection of it. Therefore, we developed
      a highly sensitive, specific sandwich ELISA system and assayed SEM in food
      matrixes. This assay facilitates the study of SEM expression in vitro and in
      vivo. In addition, the investigations would be helpful in addressing the relative
      incidence of SEM+ strains in near future.

PMID- 28444878
TI  - What do farmers' weed control decisions imply about glyphosate resistance?
      Evidence from surveys of US corn fields.
AB  - BACKGROUND: The first case of glyphosate-resistant weeds in the United States was
      documented in 1998, 2 years after the commercialization of genetically engineered
      herbicide-resistant (HR) corn and soybeans. Currently, over 15 glyphosate
      resistant weed species affect US crop production areas. These weeds have the
      potential to reduce yields, increase costs, and lower farm profitability. The
      objective of our study is to develop a behavioral model of farmers' weed
      management decisions and use it to analyze weed resistance to glyphosate in US
      corn farms. RESULTS: On average, we find that weed control increased US corn
      yields by 3700 kg ha-1 (worth approximately $US 255 ha-1 ) in 2005 and 3500 kg ha
      1 (worth approximately $US 575 ha-1 ) in 2010. If glyphosate resistant weeds were
      absent, glyphosate killed approximately 99% of weeds, on average, when applied at
      the label rate in HR production systems. Average control was dramatically lower
      in states where glyphosate resistance was widespread. CONCLUSION: We find that
      glyphosate resistance had a significant impact on weed control costs and corn
      yields of US farmers in 2005 and 2010. Published 2017. This article is a U.S.
      Government work and is in the public domain in the USA.

PMID- 28444880
TI  - Abstractband anlasslich der 49. Tagung der Deutschen Dermatologischen
      Gesellschaft, Vereinigung Deutschsprachiger Dermatologen e. V. in Berlin vom 26.
      bis 29. April 2017.

PMID- 28444879
TI  - Prioritizing treatment outcomes: How people with acne vulgaris decide if their
      treatment is working.
AB  - OBJECTIVE: To collect information about how people with acne make day-to-day
      decisions concerning the effectiveness of their treatment. METHODS: Between May
      and August 2013, an optional question was embedded in the James Lind Alliance
      Acne Priority Setting Partnership's online survey to collect treatment
      uncertainties. The question asked people with acne to "Tell us in your own words
      how you decide if your treatment has been effective." RESULTS: A total of 742
      respondents specified at least one outcome or means of assessing change (outcome
      measure). Fewer spots were the most commonly cited outcome, identified by 272
      respondents (36.7%). Other frequently mentioned outcomes were in descending
      order: less redness (19.4%), reduction in spot size (12.1%), and less
      pain/discomfort (11.4%). Signs were much more commonly used than symptoms and
      surrogate outcomes such as changes in aspects of life quality were infrequently
      mentioned. Visual inspection of the skin was the most widely adopted outcome
      measure (16.3%). CONCLUSIONS: Although the most frequently used methods map well
      onto the outcome measures adopted in the majority of acne trials, namely
      physician-assessed changes in lesion counts and global acne severity, people with
      acne often take into account several factors that cannot be assessed by a third
      party at a single point in time. The minimal use of changes in psychosocial
      wellbeing and mood may reflect that these are regarded as secondary consequences
      of improvements in appearance. The robustness of these findings now requires
      independent evaluation. If confirmed, they could form the basis of a new patient
      reported outcome measure.

PMID- 28444881
TI  - A three-lncRNA expression signature associated with the prognosis of gastric
      cancer patients.
AB  - Long noncoding RNAs (lncRNAs) have emerged as essential players in gene
      regulation. An ever-increasing number of lncRNAs has been found to be associated
      with the biogenesis and prognosis of gastric cancer (GC). We aimed to develop an
      lncRNA signature with prognostic value for survival outcomes of GC. Using an
      lncRNA mining approach, we analyzed the lncRNA expression profiles of 492 GC
      patients from the Gene Expression Omnibus (GEO), which consisted of the GSE62254
      set (N = 300) and the GSE15459 set (N = 192). The associations between the
      lncRNAs' expression and survival outcome were evaluated. A set of three lncRNAs
      (LINC01140, TGFB2-OT1, and RP11-347C12.10) was identified to significantly
      correlate with overall survival. These lncRNAs were then combined to form a
      single prognostic signature. Based on this three-lncRNA expression signature,
      patients in the GSE62254 set were classified into high- and low-risk subgroups
      with significantly different overall survival (hazard ratio [HR] = 1.93, P <
      0.001) and disease-free survival (HR = 1.91, P < 0.001). Good reproducibility for
      the prognostic value of this lncRNA signature was confirmed in the GSE15459 set.
      Further analysis showed that the prognostic value of this signature was
      independent of some clinical characteristics. Gene set enrichment analysis
      indicated that high-risk scores positively related to several molecular pathways
      of cancer metastasis. Our results suggest that this innovative lncRNA expression
      signature may be a useful biomarker for the prognosis of patients with GC based
      on bioinformatics analysis.

PMID- 28444883
TI  - Approaches for optimising intravenous iron dosing in pregnancy: a retrospective
      cohort study.
AB  - BACKGROUND: Intravenous iron is commonly utilised in pregnancy when treatment
      with oral is not tolerated or where rapid replenishment of iron stores is
      required. AIMS: To examine the relationship between doses of intravenous iron
      administered during pregnancy according to different maternal bodyweight measures
      and subsequent treatment response. METHODS: Retrospective cohort study of
      pregnant women with confirmed iron deficiency anaemia who received intravenous
      iron polymaltose at a tertiary teaching hospital in Australia from 1 January 2014
      to 31 January 2016. Diagnosis of anaemia and/or iron deficiency, infusion dosage
      characteristics and haematological parameters were collected from paper-based
      case notes and electronic records. The dose of intravenous iron administered was
      examined relative to maternal total bodyweight (TBW), ideal bodyweight (IBW)
      (equation = 45.5 kg + 0.9 kg/cm for each cm over 152 cm) and adjusted bodyweight
      (equation = IBW + [0.4 * (TBW - IBW)]). RESULTS: A total of 122 pregnancies was
      identified where women had confirmed iron deficiency anaemia and received a
      single infusion of intravenous iron polymaltose. Dose-response relationships were
      evident between change in haemoglobin from treatment until delivery and
      intravenous iron dose according to adjusted bodyweight (adjusted beta coefficient
      0.70 (95% CI 0.24-1.15)) and pre-pregnancy total bodyweight (adjusted beta
      coefficient 0.83 (95% CI 0.36-1.29)), but not ideal bodyweight (adjusted beta
      coefficient 0.37 (95% CI -0.04-0.78)). Calculating iron deficit using adjusted
      bodyweight most closely matched that based on a physiological estimate of iron
      deficit according to weight-based total blood volume. CONCLUSION: Optimal
      treatment outcomes in pregnant women requiring intravenous iron may be reached by
      dosing according to adjusted pre-pregnancy bodyweight rather than ideal
      bodyweight.

PMID- 28444884
TI  - Novel urinary alkylresorcinol metabolites as biomarkers of whole grain intake in
      free-living Swedish adults.
AB  - SCOPE: Most studies on the role of whole grain for health rely on self-reported
      intake data, which are prone to measurement errors. There is a need for dietary
      biomarkers that can provide an objective measure of intake. Alkylresorcinols (AR)
      and their main metabolites 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5
      dihydroxyphenyl)-propanoic acid (DHPPA) have been proposed as biomarkers for
      whole grain (WG) wheat and rye intake. METHODS AND RESULTS: The medium-term
      reproducibility and relative validity of four putative urinary AR metabolites
      (3,5-dihydroxycinnamic acid (DHCA), 5-(3,5-dihydroxyphenyl) pentanoic acid
      (DHPPTA), 2-(3,5-dihydroxybenzamido)acetic acid (DHBA-glycine) and 3,5
      dihydroxycinnamic acid amide (DHCA-amide)) as biomarkers for WG intake were
      investigated. Three-day weighed food records and 24-h urine samples from two
      occasions 2-3 months apart were obtained from 69 Swedish adults. WG intake was
      calculated and urinary AR metabolites were analyzed. The medium-term
      reproducibility determined for DHCA, DHPPTA, and DHBA-glycine varied from
      moderate-to-excellent (intra-class correlation coefficient = 0.63-0.85).
      Moreover, DHCA and DHPPTA excretion correlated well with self-reported total WG
      intake (r = 0.55, p < 0.001 and r = 0.42, p < 0.001, respectively). CONCLUSION:
      DHCA or DHPPTA excretion in 24-h urine might be a suitable medium- to long-term
      biomarker of WG wheat and rye intake. These findings need to be confirmed in
      populations with low and infrequent WG intake.

PMID- 28444885
TI  - Hypoxia-induced apoptosis of mouse spermatocytes is mediated by HIF-1alpha
      through a death receptor pathway and a mitochondrial pathway.
AB  - Hypoxia in vivo induces oligozoospermia, azoospermia, and degeneration of the
      germinal epithelium, but the underlying molecular mechanism of this induction is
      not fully clarified. The aim of this study was to investigate the role of the
      death receptor pathway and the mitochondrial pathway in hypoxia-induced apoptosis
      of mouse GC-2spd (GC-2) cells and the relationship between HIF-1alpha and
      apoptosis of GC-2 cells induced by hypoxia. GC-2 cells were subjected to 1%
      oxygen for 48 hr. Apoptosis was detected by flow cytometry, TUNEL staining, LDH,
      caspase-3/8/9 in the absence and presence of HIF-1alpha siRNA. The protein levels
      of apoptosis-related markers were determined by Western blot in the presence and
      absence of HIF-1alpha siRNA. Mitochondrial transmembrane potential change was
      observed by in situ JC-1 staining. Cell viability was assessed upon treatment of
      caspase-8 and 9 inhibitors. The results indicated that hypoxia at 1% oxygen for
      48 hr induced apoptosis of GC-2 cells. A prolonged exposure of GC-2 cells to
      hypoxic conditions caused downregulation of c-FLIP, Dc R2 and Bcl-2 and
      upregulation of DR5 , TRAIL, Fas, p53, and Bax, with an overproduction of caspase
      3/8/9. Moreover, hypoxia at this level had an effect on mitochondrial
      depolarization. In addition, specific inhibitors of caspase-8/9 partially
      suppressed hypoxia-induced GC-2 cell apoptosis, and the anti-apoptotic effects of
      the caspase inhibitors were additive. Of note, HIF-1alpha knockdown attenuated
      hypoxia and induced apoptosis of GC-2 cells. In conclusion, our data suggest that
      the death receptor pathway and mitochondrial pathway, which are likely mediated
      by HIF-1alpha, contribute to hypoxia-induced GC-2 cell apoptosis.

PMID- 28444886
TI  - Detection of Mycobacterium avium subsp. paratuberculosis in non-human primates.
AB  - BACKGROUND: Due to a sporadic occurrence of Mycobacterium avium subsp.
      paratuberculosis (MAP) in non-human primates (NHP), the susceptibility of
      different NHP to MAP should be investigated. METHODS: Fecal and tissue samples
      (ileum, ileocecal lymph node, bone marrow) of 20 animals (seven species) were
      analyzed by IS900-based PCRs and sequenced. Samples of MAP PCR positive NHP were
      further cultivated. RESULTS: MAP DNA was detectable in two animals; the ileum of
      a cottontop tamarin and the bone marrow of a common marmoset. Cultivation of MAP
      failed. Sequence analysis revealed 100% homology to the MAP-K10 sequence.
      Pathohistological examinations offered no direct correlation to a MAP infection.
      CONCLUSIONS: MAP was detected for the first time in a common marmoset. But as
      both NHP suffered from other diseases, an asymptomatic infection with MAP was
      assumed. The detection of MAP in the bone marrow might play a role in
      establishing latent paratuberculosis, as known from tuberculosis.

PMID- 28444887
TI  - Morphological study of the atrioventricular conduction system and Purkinje fibers
      in yak.
AB  - We studied the morphology of the atrioventricular conduction system (AVCS) and
      Purkinje fibers of the yak. Light and transmission electron microscopy were used
      to study the histological features of AVCS. The distributional characteristics of
      the His-bundle, the left bundle branch (LBB), right bundle branch (RBB), and
      Purkinje fiber network of yak hearts were examined using gross dissection, ink
      injection, and ABS casting. The results showed that the atrioventricular node
      (AVN) of yak located in the right side of interatrial septum and had a flattened
      ovoid shape. The AVN of yak is composed of the slender, interweaving cells formed
      almost entirely of the transitional cells (T-cells). The His-bundle extended from
      the AVN, and split into left LBB and RBB at the crest of the interventricular
      septum. The LBB descended along the left side of interventricular septum. At
      approximately the upper 1/3 of the interventricular septum, the LBB typically
      divided into three branches. The RBB ran under the endocardium of the right side
      of interventricular septum, and extended to the base of septal papillary muscle,
      passed into the moderator band, crossed the right ventricular cavity to reach the
      base of anterior papillary muscle, and divided into four fascicles under the
      subendocardial layer. The Purkinje fibers in the ventricle formed a complex
      spatial network. The distributional and cellular component characteristics of the
      AVCS and Purkinje fibers ensured normal cardiac function.

PMID- 28444888
TI  - BacteRiophage EXclusion (BREX): A novel anti-phage mechanism in the arsenal of
      bacterial defense system.
AB  - The arm race between bacteria and phages leads to the development of many phage
      resistance mechanisms. Bacteria are perpetually changing their strategy to avert
      phage infection and killing. Recently, a study published that shed light on a
      novel bacterial defense system called bacteriophage exclusion (BREX). BREX system
      is a six-gene cassette in Bacillus cereus which provides complete phage
      resistance to a broad range of phages, including lytic and temperate ones. It is
      a novel defense strategy which involves DNA methylation of the host cell and
      block phage DNA replication.

PMID- 28444889
TI  - Invasive fungal infections in paediatric patients treated with macromolecular
      immunomodulators other than tumour necrosis alpha inhibitors.
AB  - An expanding list of immunomodulatory or immunosuppressive monoclonal antibodies
      (mAbs) and biologic therapeutics is currently entering clinical practice,
      particularly in the areas of oncology, transplantation and autoimmune disorders.
      These agents are directed against molecules or cells involved in inflammation and
      immunity and may therefore be associated with serious and opportunistic
      infections. The purpose of this review was to critically analyse the literature
      on invasive fungal infections (IFIs) occurring in association with mAbs and
      fusion proteins other than tumour necrosis alpha (TNF-alpha) inhibitors,
      including therapeutics modulating T-cell-mediated pathologies (muromonab,
      abatacept, belatacept, ipilimumab, basiliximab, daclizumab), inducing lymphopenia
      (alemtuzumab), depleting CD20+ B cells (rituximab) and interfering with various
      targets (anakinra, natalizumab, blodalumab, ixekizumab and others) with a focus
      on children, and to provide a framework of evaluating the risk for IFIs in this
      population.

PMID- 28444890
TI  - Utilizing PBPK Modeling to Evaluate the Potential of a Significant Drug-Drug
      Interaction Between Clopidogrel and Dasabuvir: A Scientific Perspective.
AB  - Dasabuvir, a component of VIEKIRA PAK, is a substrate of CYP2C8 enzymes.
      Prescribing information for VIEKIRA PAK contraindicates gemfibrozil, a strong
      CYP2C8 inhibitor, because coadministration significantly increases dasabuvir
      exposures, which may increase the risk of QT prolongation. Clopidogrel may
      increase dasabuvir exposures primarily due to CYP2C8 inhibition by clopidogrel
      acyl-beta-D-glucuronide. This commentary outlines the US Food and Drug
      Administration (FDA) interdisciplinary review team's scientific perspective to
      address the potential for a significant drug-drug interaction (DDI) between
      clopidogrel and VIEKIRA PAK.

PMID- 28444891
TI  - Chemistry of the 5g Elements: Relativistic Calculations on Hexafluorides.
AB  - A Periodic System was proposed for the elements 1-172 by Pyykko on the basis of
      atomic and ionic calculations. In it, the elements 121-138 were nominally
      assigned to a 5g row. We now perform molecular, relativistic four-component DFT
      calculations and find that the hexafluorides of the elements 125-129 indeed enjoy
      occupied 5g states.

PMID- 28444892
TI  - Catalytic Mechanism of Salicylate Dioxygenase: QM/MM Simulations Reveal the
      Origin of Unexpected Regioselectivity of the Ring Cleavage.
AB  - Salicylate 1,2-dioxygenase (SDO) was the first enzyme discovered, in the family
      of iron dioxygenases, to catalyze the ring cleavage of a monohydroxylated
      aromatic compound, salicylate, without a proton donor. Salicylate is not electron
      rich like the familiar dihydroxy or aromatic substrates with an electron-donating
      group that are utilized in the well-known dioxygenases. SDO carries out the
      intramolecular C-C bond cleavage in salicylate bearing the OH and COOH groups
      with high regioselectivity in comparison with the extradiol and intradiol
      dioxygenases. The catalytic cleavage of a nonactivated substrate like salicylate
      that lacks an electron-donating group, also in the absence of a proton source,
      raises many puzzling questions about the oxy intermediates in the reaction
      pathway of dioxygenase enzymes in general. To answer these fundamental queries,
      we have investigated the full catalytic mechanism of SDO by a combination of
      quantum mechanics and molecular mechanics (QM/MM) calculations. Herein, our QM/MM
      study has several unexpected and interesting implications for the mechanistic
      pathway of SDO in comparison to the experimental observations. Importantly, it
      unravels the basis for the unexpected "intra"-cleavage regioselectivity in SDO.
      Ostensibly a similar alkylperoxo intermediate is formed in SDO much like in the
      extradiol and intradiol dioxygenases. In stark contrast to the two diol enzymes,
      the O-O bond breaking leads to an unprotonated gem-hydroxy carboxylate
      intermediate, a paradigm analogue of the elusive gem diol intermediate. This
      unprotonated gem-hydroxy carboxylate intermediate exclusively dictates the C-C
      cleavage regiospecificity in SDO, which is unprecedented in the family of
      dioxygenases. It forms a seven-membered lactone species, which eventually forms
      the ring-cleavage final product by incorporation of two oxygen atoms in the
      salicylate. Thus, our computational study unravels a detailed reaction pathway of
      the oxidative cleavage of salicylate without a proton source by identifying the
      hitherto elusive intermediates in the catalytic cycle of SDO with testable
      predictions. Moreover, we describe the atomistic origin of the new catalytic role
      of Arg127 in the catalysis and regioselectivity of SDO. It also rationalizes the
      formation of a side product without invoking a dioxetane intermediate. This study
      is important from a fundamental perspective and opens up a new window in the
      mechanism of the family of dioxygenase enzymes.

PMID- 28444893
TI  - Catalytic Reductive Synthesis and Direct Derivatization of Unprotected
      Aminoindoles, Aminopyrroles, and Iminoindolines.
AB  - A titanium(III)-catalyzed radical cyclization to unprotected 3-aminoindoles, 3
      aminopyrroles, or 3-iminoindolines is reported. The reaction is non-hazardous,
      scalable, and allows facile isolation of the free products by extraction. The
      method is demonstrated on a large substrate scope and it further allows the
      direct installation of various nitrogen protecting groups or the synthesis of
      building blocks for peptide chemistry in a single sequence. Fused bisindoles can
      be directly accessed from the cyclization products.

PMID- 28444894
TI  - Species ecological similarity modulates the importance of colonization history
      for adaptive radiation.
AB  - Adaptive radiation is an important evolutionary process, through which a single
      ancestral lineage rapidly gives rise to multiple newly formed lineages that
      specialize in different niches. In the first-arrival hypothesis, David Lack
      emphasized the importance of species colonization history for adaptive radiation,
      suggesting that the earlier arrival of a diversifying species would allow it to
      radiate to a greater extent. Here, we report on the first rigorous experimental
      test of this hypothesis, using the rapidly evolving bacterium Pseudomonas
      fluorescens SBW25 and six different bacterial competitors. We show that the
      earlier arrival of P. fluorescens facilitated its diversification. Nevertheless,
      significant effects of colonization history, which led to alternative
      diversification trajectories, were observed only when the competitors shared
      similar niche and competitive fitness with P. fluorescens. These results
      highlight the important role of species colonization history, modified by their
      ecological differences, for adaptive radiation.

PMID- 28444895
TI  - Intraocular pressure following intrastromal corneal ring segments.

PMID- 28444896
TI  - Agreement between finger plethysmography- and brachial oscillometry-derived blood
      pressure measurements.
AB  - PURPOSE: Blood pressure (BP) is commonly assessed by brachial oscillometry in
      clinical practice, whereas in physiological studies, finger plethysmography is
      often employed. This study assessed the limits of agreement between BP metrics
      obtained from each device. METHODS: In 96 participants, we simultaneously
      recorded BP by brachial oscillometry (BP+; Uscom, Sydney, NSW, Australia) and
      finger plethysmography (Finometer MIDI, MLE1054-V; Finapres Medical Systems B.V.,
      Amsterdam, the Netherlands). Agreement between the two devices was assessed by
      correlation and Bland-Altman analysis. We assessed average BP differences between
      the two devices using the criteria of the Association for the Advancement of
      Medical Instruments (AAMI), which require systolic and diastolic BP differences
      to be within <=5 +/- 8 (mean +/- SD). RESULTS: Bland-Altman analysis showed wide
      limits of agreement (+/-~17 mmHg or greater) between finger-derived brachial and
      oscillometric BP. Both systolic and mean BP exhibited positive proportional
      biases (both P<0.05). Systolic BP differed significantly between devices (7.4 +/-
      17.7 mmHg, P<0.001), which did not meet the AAMI criteria. No mean bias was
      observed for diastolic BP (-1.5 +/- 8.6 mmHg, P = 0.097), and the SD of +/-8.6
      mmHg is potentially acceptable given the finger signal may be expected to capture
      biological variability in BP. Mean BP showed poor concordance (3.7 +/- 10.5 mmHg,
      P<0.001). CONCLUSIONS: These findings indicate that systolic and mean BP
      measurements made by brachial oscillometry do not agree with those from finger
      plethysmography. In contrast, diastolic BP values show acceptable agreement.

PMID- 28444897
TI  - Aging asexual lineages and the evolutionary maintenance of sex.
AB  - Finite populations of asexual and highly selfing species suffer from a reduced
      efficacy of selection. Such populations are thought to decline in fitness over
      time due to accumulating slightly deleterious mutations or failing to adapt to
      changing conditions. These within-population processes that lead nonrecombining
      species to extinction may help maintain sex and outcrossing through species level
      selection. Although inefficient selection is proposed to elevate extinction rates
      over time, previous models of species selection for sex assumed constant
      diversification rates. For sex to persist, classic models require that asexual
      species diversify at rates lower than sexual species; the validity of this
      requirement is questionable, both conceptually and empirically. We extend past
      models by allowing asexual lineages to decline in diversification rates as they
      age, that is nonrecombining lineages "senesce" in diversification rates. At
      equilibrium, senescing diversification rates maintain sex even when asexual
      lineages, at young ages, diversify faster than their sexual progenitors. In such
      cases, the age distribution of asexual lineages contains a peak at intermediate
      values rather than showing the exponential decline predicted by the classic
      model. Coexistence requires only that the average rate of diversification in
      asexuals be lower than that of sexuals.

PMID- 28444898
TI  - An Isoquinolin-1(2H)-Imine Derivative Induces Cell Death via Generation of
      Reactive Oxygen Species and Activation of JNK in Human A549 Cancer Cells.
AB  - Compound 11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H
      pyrimido[1,2-b]isoquinoline-8-carbonitrile (HC6h) is a novel polyhalo 1,3
      diazaheterocycle fused isoquinolin-1(2H)-imines derivative, which displays good
      anticancer activity and low toxicity in vivo. However, the underlying anticancer
      mechanisms have not previously been identified. The proliferation of A549 was
      assessed by MTT assay. The reactive oxygen species (ROS) level was assessed in
      A549 with a H2 DCFDA probe. Mitochondrial membrane potential was measured using
      the JC-1 staining. Apoptosis were measured by annexin-V/PI assay and autophagy by
      acridine orange staining and GFP-LC3 fluorescence assay. The expression of
      autophagic and apoptotic proteins was determined by Western blot. The compound
      HC6h increased accumulation of vesicles, acridine orange-stained cells and LC3-II
      in A549 cells. Inhibition of compound HC6h-induced autophagy by bafilomycin A1
      increased apoptosis. Compound HC6h enhanced activation of caspase-3, caspase-9
      and PARP cleavage in A549 cells. Compound HC6h leads to the rapid generation of
      intracellular ROS. Moreover, compound HC6h induced phosphorylation of JNK and was
      conferred by the increased ROS levels. Furthermore, down-regulation of JNK
      attenuated autophagic and apoptotic effect in response to HC6h. The induction of
      ROS upon HC6h treatment leads to the activation of JNK that mediates autophagy
      and apoptosis in human A549 cancer cells. J. Cell. Biochem. 118: 4394-4403, 2017.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 28444900
TI  - Lactosylceramide-Induced Phosphorylation Signaling to Group IVA Phospholipase A2
      via Reactive Oxygen Species in Tumor Necrosis Factor-alpha-Treated Cells.
AB  - The activity of alpha-type cytosolic phospholipase A2 (cPLA2 alpha, group IVA
      PLA2 ), which releases arachidonic acid (AA), is mainly regulated by the Ca2+ 
      induced intracellular translocation/attachment of the enzyme to substrate
      membranes and its phosphorylation. We previously reported that tumor necrosis
      factor-alpha (TNFalpha) stimulated the formation of lactosylceramide (LacCer) in
      L929 fibroblast cells, and this lipid directly bound with and activated cPLA2
      alpha [Nakamura et al. [2013] J. Biol. Chem. 288:23264-23272]. We herein
      investigated the role of phosphorylation signaling in the TNFalpha/LacCer-induced
      activation of cPLA2 alpha in cells. TNFalpha-treated L929 cells released AA via
      the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and
      cPLA2 alpha, while a treatment with LacCer alone released AA in a similar manner.
      The TNFalpha-induced responses including release of AA were decreased by the
      inhibition of LacCer synthesis. The treatment with TNFalpha and LacCer increased
      the levels of reactive oxygen species (ROS), and the reduction/scavenging of ROS
      decreased the phosphorylation cascade and release of AA in TNFalpha/LacCer
      treated L929 cells. In the cell line CHO, the treatment with LacCer stimulated
      the phosphorylation cascade and release of AA via the formation of ROS.
      Treatments with the anti-LacCer antibody and 4beta-phorbol 12-myristate 13
      acetate stimulated the phosphorylation cascade, but did not release AA by itself.
      When combined with the Ca2+ ionophore A23187, treatments with the anti-LacCer
      antibody and 4beta-phorbol 12-myristate 13-acetate released AA. These results,
      including our previous findings, showed that LacCer alone simultaneously
      stimulates two processes to activate cPLA2 alpha: a phosphorylation signal and
      attachment of the enzyme to substrate membranes. J. Cell. Biochem. 118: 4370
      4382, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28444899
TI  - Focal Adhesion Kinase (FAK) tyrosine 397E mutation restores the vascular leakage
      defect in endothelium-specific FAK-kinase dead mice.
AB  - Focal adhesion kinase (FAK) inhibitors have been developed as potential
      anticancer agents and are undergoing clinical trials. In vitro activation of the
      FAK kinase domain triggers autophosphorylation of Y397, Src activation, and
      subsequent phosphorylation of other FAK tyrosine residues. However, how FAK Y397
      mutations affect FAK kinase-dead (KD) phenotypes in tumour angiogenesis in vivo
      is unknown. We developed three Pdgfb-iCreert -driven endothelial cell (EC)
      specific, tamoxifen-inducible homozygous mutant mouse lines: FAK wild-type (WT),
      FAK KD, and FAK double mutant (DM), i.e. KD with a putatively phosphomimetic
      Y397E mutation. These ECCre+;FAKWT/WT , ECCre+;FAKKD/KD and ECCre+;FAKDM/DM mice
      were injected subcutaneously with syngeneic B16F0 melanoma cells. Tumour growth
      and tumour blood vessel functions were unchanged between ECCre+;FAKWT/WT and
      ECCre-;FAKWT/WT control mice. In contrast, tumour growth and vessel density were
      decreased in ECCre+;FAKKD/KD and ECCre+;FAKDM/DM mice, as compared with Cre -
      littermates. Despite no change in the percentage of perfused vessels or pericyte
      coverage in either genotype, tumour hypoxia was elevated in ECCre+;FAKKD/KD and
      ECCre+;FAKDM/DM mice. Furthermore, although ECCre+;FAKKD/KD mice showed reduced
      blood vessel leakage, ECCre+;FAKDM/DM and ECCre-;FAKDM/DM mice showed no
      difference in leakage. Mechanistically, fibronectin-stimulated Y397
      autophosphorylation was reduced in Cre+;FAKKD/KD ECs as compared with
      Cre+;FAKWT/WT cells, with no change in phosphorylation of the known Src targets
      FAK-Y577, FAK-Y861, FAK-Y925, paxillin-Y118, p130Cas-Y410. Cre+;FAKDM/DM ECs
      showed decreased Src target phosphorylation levels, suggesting that the Y397E
      substitution actually disrupted Src activation. Reduced VE-cadherin-pY658 levels
      in Cre+;FAKKD/KD ECs were rescued in Cre+FAKDM/DM ECs, corresponding with the
      rescue in vessel leakage in the ECCre+;FAKDM/DM mice. We show that EC-specific
      FAK kinase activity is required for tumour growth, angiogenesis, and vascular
      permeability. The ECCre+;FAKDM/DM mice restored the KD-dependent tumour vascular
      leakage observed in ECCre+;FAKKD/KD mice in vivo. This study opens new fields in
      in vivo FAK signalling. (c) 2017 The Authors. The Journal of Pathology published
      by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and
      Ireland.

PMID- 28444901
TI  - PGE2 Receptor Subtype 1 (EP1) Regulates Mesenchymal Stromal Cell Osteogenic
      Differentiation by Modulating Cellular Energy Metabolism.
AB  - Mesenchymal stromal cells (MSCs) are multipotent progenitors capable of
      differentiation into osteoblasts and can potentially serve as a source for cell
      based therapies for bone repair. Many factors have been shown to regulate MSC
      differentiation into the osteogenic lineage such as the Cyclooxygenase-2
      (COX2)/Prostaglandin E2 (PGE2) signaling pathway that is critical for bone
      repair. PGE2 binds four different receptors EP1-4. While most studies focus on
      the role PGE2 receptors EP2 and EP4 in MSC differentiation, our study focuses on
      the less studied, receptor subtype 1 (EP1) in MSC function. Recent work from our
      laboratory showed that EP1-/- mice have enhanced fracture healing, stronger
      cortical bones, higher trabecular bone volume and increased in vivo bone
      formation, suggesting that EP1 is a negative regulator of bone formation. In this
      study, the regulation of MSC osteogenic differentiation by EP1 receptor was
      investigated using EP1 genetic deletion in EP1-/- mice. The data suggest that EP1
      receptor functions to maintain MSCs in an undifferentiated state. Loss of the EP1
      receptor changes MSC characteristics and permits stem cells to undergo more rapid
      osteogenic differentiation. Notably, our studies suggest that EP1 receptor
      regulates MSC differentiation by modulating MSC bioenergetics, preventing the
      shift to mitochondrial oxidative phosphorylation by maintaining high Hif1alpha
      activity. Loss of EP1 results in inactivation of Hif1alpha, increased oxygen
      consumption rate and thus increased osteoblast differentiation. J. Cell. Biochem.
      118: 4383-4393, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28444902
TI  - Trajectory of social inequalities in the treatment of dental caries among
      preschool children in Japan.
AB  - OBJECTIVES: The longitudinal trend of dental health inequalities among preschool
      children has not been described. In this study, we aimed to measure the
      trajectory of both relative and absolute inequalities in caries treatment among
      preschool children in Japan. METHODS: We used data from the Longitudinal Survey
      of Babies in the 21st Century (LSB21), which is an ongoing national
      representative longitudinal study. The target population was families residing in
      Japan with newborn baby/babies born between 10 January and 17 January or 10 July
      and 17 July 2001. Data regarding caries treatment history and socioeconomic
      status (SES) were collected using a self-reported questionnaire. SES was assessed
      on the basis of the parents' educational attainment. In total, 35 260 children
      were followed from 2.5 to 5.5 years through annual surveys. To evaluate absolute
      and relative inequalities, we calculated the slope index of inequality (SII) and
      relative index of inequality (RII), respectively. RESULTS: The rate of caries
      treatment at the age of 2.5 years was <10% for all SES groups; this increased to
      more than 30% at 5.5 years of age. Children with lower SES received more frequent
      caries treatment, and both absolute and relative social inequalities were
      statistically significant. SII showed a significant increase throughout the
      follow-up period, with values of 4.13% (95% confidence interval [CI], 3.16; 5.09)
      and 15.50% (95% CI, 13.68; 17.32) at 2.5 and 5.5 years of age, respectively. In
      contrast, RII decreased with an increase in the treatment rate for all groups,
      with values of 1.83 (95% CI, 1.59; 2.11) and 1.53 (95% CI, 1.46; 1.61) at 2.5 and
      5.5 years of age, respectively. CONCLUSION: Our results suggest that the rate of
      caries treatment is higher for preschool children with lower SES in Japan, with
      significant widening of absolute inequalities along with the growth of the
      children.

PMID- 28444903
TI  - Electrospray ionization mass spectrometry for the hydrolysis complexes of
      cisplatin: implications for the hydrolysis process of platinum complexes.
AB  - Non-enzyme-dependent hydrolysis of the drug cisplatin is important for its mode
      of action and toxicity. However, up until today, the hydrolysis process of
      cisplatin is still not completely understood. In the present study, the
      hydrolysis of cisplatin in an aqueous solution was systematically investigated by
      using electrospray ionization mass spectrometry coupled to liquid chromatography.
      A variety of previously unreported hydrolysis complexes corresponding to
      monomeric, dimeric and trimeric species were detected and identified. The
      characteristics of the Pt-containing complexes were investigated by using
      collision-induced dissociation (CID). The hydrolysis complexes demonstrate
      distinctive and correlative CID characteristics, which provides tools for an
      informative identification. The most frequently observed dissociation mechanism
      was sequential loss of NH3 , H2 O and HCl. Loss of the Pt atom was observed as
      the final step during the CID process. The formation mechanisms of the observed
      complexes were explored and experimentally examined. The strongly bound dimeric
      species, which existed in solution, are assumed to be formed from the clustering
      of the parent compound and its monohydrated or dihydrated complexes. The role of
      the electrospray process in the formation of some of the observed ions was also
      evaluated, and the electrospray ionization-related cold clusters were identified.
      The previously reported hydrolysis equilibria were tested and subsequently
      refined via a hydrolysis study resulting in a renewed mechanistic equilibrium
      system of cisplatin as proposed from our results. Copyright (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 28444904
TI  - A bell pepper cultivar tolerant to chilling enhanced nitrogen allocation and
      stress-related metabolite accumulation in the roots in response to low root-zone
      temperature.
AB  - Two bell pepper (Capsicum annuum) cultivars, differing in their response to
      chilling, were exposed to three levels of root-zone temperatures. Gas exchange,
      shoot and root phenology, and the pattern of change of the central metabolites
      and secondary metabolites caffeate and benzoate in the leaves and roots were
      profiled. Low root-zone temperature significantly inhibited gaseous exchange,
      with a greater effect on the sensitive commercial pepper hybrid (Canon) than on
      the new hybrid bred to enhance abiotic stress tolerance (S103). The latter was
      less affected by the treatment with respect to plant height, shoot dry mass, root
      maximum length, root projected area, number of root tips and root dry mass. More
      carbon was allocated to the leaves of S103 than nitrogen at 17 degrees C, while
      in the roots at 17 degrees C, more nitrogen was allocated and the ratio between
      C/N decreased. Metabolite profiling showed greater increase in the root than in
      the leaves. Leaf response between the two cultivars differed significantly. The
      roots accumulated stress-related metabolites including gamma-aminobutyric acid
      (GABA), proline, galactinol and raffinose and at chilling (7 degrees C) resulted
      in an increase of sugars in both cultivars. Our results suggest that the enhanced
      tolerance of S103 to root cold stress, reflected in the relative maintenance of
      shoot and root growth, is likely linked to a more effective regulation of
      photosynthesis facilitated by the induction of stress-related metabolism.

PMID- 28444905
TI  - The value of a combined word recognition and knowledge measure to understand
      characteristics of our patients' oral health literacy.
AB  - OBJECTIVE: The objective of the analysis was to examine the association between
      sociodemographic and dental understanding and utilization characteristics and
      lower oral health literacy (HL) and knowledge. METHODS: The cross-sectional
      Multicenter Oral Health Literacy Research Study (MOHLRS) recruited and
      interviewed 923 English-speaking, initial care-seeking adults. The questionnaire
      included participant sociodemographic characteristics, measures of the
      participant's understanding and utilization of dentistry, and two oral HL
      measures, the Rapid Estimate of Adult Literacy in Medicine and Dentistry (REALM
      D) and the Comprehensive Measure of Oral Health Knowledge (CMOHK), which were
      combined into a new composite HL and knowledge measure, the MOHLR-K. RESULTS: In
      adjusted multivariable analysis, persons who reported more understanding of
      dentist instructions had higher mean scores for all HL measures. Subjects
      reporting the highest level of understanding had greater scores by an average of
      1.6 points for the MOHLR-K (95% CI: 0.85-2.40, P<.01), 2.11 points for REALMD-20
      (95% CI: 0.75-3.48, P<.01) and 2.20 points for CMOHK (95% CI: 1.01-3.40, P<.01)
      after controlling for demographic and other dental understanding and utilization
      factors. Persons who reported history of tooth decay had higher MOHLR-K scores by
      an average of about 0.77 points (95% CI: 0.49-1.04, P<.01), higher REALMD-20
      scores by 0.54 points (95% CI: 0.12-0.95, P=.01) and higher CMOHK scores by 1.22
      points (95% CI: 0.82-1.63, P<.01) as compared to persons without tooth decay
      history after controlling for the other factors. Persons who had support all of
      the time for travel to the dentist had higher scores by an average of about 0.5
      points for the MOHLR-K (95% CI: 0.04-0.96, P=.03) and about 0.89 points for the
      REALMD-20 (95% CI: 0-1.79, P=.05) as compared to subjects with no support after
      controlling for other factors. Report of periodontal history, financial
      challenges to delay a dental visit and dental utilization were not significantly
      associated with any of the HL measures once the other factors were adjusted for
      in the model. CONCLUSION: The analysis confirmed that pronunciation of medical
      and dental terms may not fully reflect comprehension and revealed that
      understanding both patients' sociodemographic and dental understanding and
      utilization factors, such as transportation to the dental office associated with
      lower oral HL and knowledge, could help the profession develop appropriate clear
      language programmes to improve access to dental care for vulnerable populations.

PMID- 28444906
TI  - Carbamoyl phosphate synthetase 1 deficiency diagnosed by whole exome sequencing.
AB  - BACKGROUND: Carbamoyl Phosphate Synthetase 1 deficiency (CPS1D) is a rare
      autosomal recessive inborn metabolic disease characterized mainly by
      hyperammonemia. The fatal nature of CPS1D and its similar symptoms with other
      urea cycle disorders (UCDs) make its diagnosis difficult, and the molecular
      diagnosis is hindered due to the large size of the causative gene CPS1.
      Therefore, the objective of the present study was to investigate the clinical
      applicability of exome sequencing in molecular diagnosis of CPS1D in Chinese
      population. METHODS: We described two Chinese neonates presented with
      unconsciousness and drowsiness due to deepening encephalopathy with
      hyperammonemia. Whole exome sequencing was performed. Candidate mutations were
      validated by Sanger sequencing. In-silicon analysis was processed for the
      pathogenicity predictions of the identified mutations. RESULTS: Two compound
      heterozygous mutations in the gene carbamoyl phosphate synthetase 1(CPS1) were
      identified. One is in Case 1 with two novel missense mutations (c.2537C>T, p.
      Pro846Leu and c.3443T>A, p.Met1148Lys), and the other one is in Case 2 with a
      novel missense mutation (c.1799G>A, p.Cys600Tyr) and a previously reported 12-bp
      deletion (c.4088_4099del, p.Leu 1363_Ile1366del). Bioinformatics deleterious
      predictions indicated pathogenicity of the missense mutations. Conversation
      analysis and homology modeling showed that the substituted amino acids were
      highly evolutionary conserved and necessary for enzyme stability or function.
      CONCLUSION: The present study initially and successfully applied whole exome
      sequencing to the molecular diagnosis of CPS1D in Chinese neonates, indicating
      its applicability in cost-effective molecular diagnosis of CPS1D. Three novel
      pathogenic missense mutations were identified, expanded the mutational spectrum
      of the CPS1 gene.

PMID- 28444907
TI  - Plant reproduction is altered by simulated herbicide drift to constructed plant
      communities.
AB  - Herbicide drift may have unintended impacts on native vegetation, adversely
      affecting individual species and plant communities. To determine the potential
      ecological effects of herbicide drift, small plant community plots were
      constructed using 9 perennial species found in different Willamette Valley (OR,
      USA) grassland habitats. Studies were conducted at 2 Oregon State University
      (Corvallis, OR, USA) farms in 2 separate years, with single and combined
      treatments of 0.01 to 0.2* field application rates (f.a.r.) of 1119 g ha-1 for
      glyphosate (active ingredient [a.i.] of 830 g ha-1 acid glyphosate) and 560 g ha
      1 a.i. for dicamba. Plant responses were percentage of cover, number of
      reproductive structures, mature and immature seed production, and vegetative
      biomass. Herbicide effects differed with species, year, and, to a lesser extent,
      farm. Generally, 0.1 to 0.2* f.a.r. of the herbicides were required to affect
      reproduction in Camassia leichtlinii, Elymus glaucus, Eriophyllum lanatum,
      Festuca idahoensis, Iris tenax, and Prunella vulgaris. Eriophyllum lanatum also
      had a significant increase in percentage of immature seed dry weight with 0.01*
      f.a.r. of dicamba or the combination of glyphosate plus dicamba. Other species
      showed similar trends, but fewer significant responses. These studies indicated
      potential effects of low levels of herbicides on reproduction of native plants,
      and demonstrated a protocol whereby species growing in a constructed plant
      community can be evaluated for ecological responses. Environ Toxicol Chem
      2017;36:2799-2813. Published 2017 SETAC. This article is a US government work
      and, as such, is in the public domain in the United States of America.

PMID- 28444908
TI  - Micelles of the chiral biocompatible surfactant (1R,2S)-dodecyl(2-hydroxy-1
      methyl-2-phenylethyl)dimethylammonium bromide (DMEB): molecular dynamics and
      fragmentation patterns in the gas phase.
AB  - RATIONALE: The study of self-assembly processes of surfactant molecules in the
      gas phase is of great interest for several theoretical and technological reasons
      related to their possible exploitation as drug carriers, protein shields and
      cleaning agents in the gas phase. METHODS: The stability and fragmentation
      patterns of singly and multiply charged (either positively or negatively)
      aggregates of the surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2
      phenylethyl)dimethyl ammonium bromide (DMEB) in the gas phase have been studied
      by ion mobility mass spectrometry and tandem mass spectrometry. Molecular
      dynamics (MD) simulations of positively and negatively singly and multiply
      charged DMEB aggregates have been performed to obtain structural and energetics
      information. Finally, in order to ascertain some clues on the DMEB growth
      mechanism, quantum mechanics calculations were carried out. RESULTS: It has been
      evidenced that positively and negatively singly charged aggregates at low
      collision energy decompose preferentially by loss of only one DMEB molecule.
      Increasing the collision energy, the loss of neutrals becomes increasingly
      abundant. Multiply charged DMEB aggregates are unstable and decompose forming
      singly charged monomers or dimers. MD simulations show reverse micelle-like
      structures with polar heads somewhat segregated into the aggregate interior.
      Finally, a good correlation between experimental and calculated collisional cross
      sections (CCS) was found. CONCLUSIONS: The fragmentation pathways of DMEB charged
      species evidenced for singly charged aggregates exhibit features similar to that
      of other detergent aggregates, but multiply charged aggregates showed a system
      specific behavior. QM calculations on the optimized structures (21+ , 31+ , 11-
      and 21- ) indicate that the most determinant interactions are due to an OH---Br
      hydrogen bonding that is also involved in the link between monomeric DMEB units.
      The MD models gave CCS values in good agreement with experimental ones, evidenced
      by a less strict reverse micelle-like structure and a reasonably spread bromine
      anion distribution Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28444909
TI  - The histone methyltransferase EZH2 is a therapeutic target in small cell
      carcinoma of the ovary, hypercalcaemic type.
AB  - Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a rare but
      aggressive and untreatable malignancy affecting young women. We and others
      recently discovered that SMARCA4, a gene encoding the ATPase of the SWI/SNF
      chromatin-remodelling complex, is the only gene recurrently mutated in the
      majority of SCCOHT. The low somatic complexity of SCCOHT genomes and the
      prominent role of the SWI/SNF chromatin-remodelling complex in transcriptional
      control of genes suggest that SCCOHT cells may rely on epigenetic rewiring for
      oncogenic transformation. Herein, we report that approximately 80% (19/24) of
      SCCOHT tumour samples have strong expression of the histone methyltransferase
      EZH2 by immunohistochemistry, with the rest expressing variable amounts of EZH2.
      Re-expression of SMARCA4 suppressed the expression of EZH2 in SCCOHT cells. In
      comparison to other ovarian cell lines, SCCOHT cells displayed hypersensitivity
      to EZH2 shRNAs and two selective EZH2 inhibitors, GSK126 and EPZ-6438. EZH2
      inhibitors induced cell cycle arrest, apoptosis, and cell differentiation in
      SCCOHT cells, along with the induction of genes involved in cell cycle
      regulation, apoptosis, and neuron-like differentiation. EZH2 inhibitors
      suppressed tumour growth and improved the survival of mice bearing SCCOHT
      xenografts. Therefore, our data suggest that loss of SMARCA4 creates a dependency
      on the catalytic activity of EZH2 in SCCOHT cells and that pharmacological
      inhibition of EZH2 is a promising therapeutic strategy for treating this disease.
      Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 28444911
TI  - Response to the letter to the editor by D. Yuan: "Risk of high altitude pulmonary
      edema and telomere length".

PMID- 28444910
TI  - Characterization of porcine endogenous retrovirus expression in neonatal and
      adult pig pancreatic islets.
AB  - BACKGROUND: Pig islets represent an alternative to the current modes of treatment
      for patients with diabetes. However, the concerns over pathogen transmission
      including that of PERV limit their immediate, widespread usage in humans. It has
      been previously demonstrated that PERV copy number and particularly expression
      levels can vary considerably between individuals and within different tissues of
      a single animal. In general, expression levels have been found to be particularly
      low in the pancreas compared to other porcine tissues suggesting a reduced risk
      associated with the use of this tissue. Data regarding this crucial aspect,
      however, remain limited and little is known about PERV status of islets
      themselves, which represent the final product to be transplanted. In addition,
      comparative analysis of the PERV status of neonatal piglets with adults is
      important as they are increasingly considered as potential islet donors for
      xenotransplantation. METHODS: Tissue samples from 51 neonatal piglets (age
      between 14 and 21 days) and 29 adult pigs were collected from Belgian landrace
      pigs used for pancreas procurement and islet isolation. Tissue biopsies were used
      to extract DNA for PERV copy number quantification by qPCR and RNA for PERV
      expression by qRT-PCR. RESULTS: As expected, PERV expression demonstrated great
      variation and was significantly lower in pancreas compared to other tissues. More
      importantly, PERV RNA expression was found to be specifically enriched in
      pancreatic islets reaching values similar to those found in other tissues such as
      liver and kidney. Interestingly, this expression was not coupled with the
      detection of reverse transcriptase in islet cultures or indeed detection of PERV
      virus. Lung, spleen, and lymph node consistently showed the highest levels of
      PERV expression. Comparison of PERV in neonatal and adult pigs showed that copy
      number did not vary significantly from birth to adulthood. PERV expression on the
      other hand was significantly lower in neonatal pig islets compared to adult
      islets and did not increase over the period of culture. CONCLUSION: Our study
      confirms the low level of PERV expression in whole pancreas in a large population
      of both neonatal and adult pigs (n=80). The level of PERV expression was however
      higher in the endocrine tissue than in the exocrine cells. There was no
      correlation between PERV status in donor PBMCs and islet cells, and no evidence
      of active replication in in vitro regardless of PERV expression in islet cells.
      Moreover, neonatal pig islets were found to have significantly lower PERV
      expression compared to adult islets. Neonatal islets have been suggested as the
      best choice for xenotransplantation in terms of economic and procurement
      considerations; the PERV status reported here would also potentially support
      their use.

PMID- 28444912
TI  - Whole genome sequencing reveals a novel deletion variant in the KIT gene in
      horses with white spotted coat colour phenotypes.
AB  - White spotting phenotypes in horses can range in severity from the common white
      markings up to completely white horses. EDNRB, KIT, MITF, PAX3 and TRPM1
      represent known candidate genes for such phenotypes in horses. For the present
      study, we re-investigated a large horse family segregating a variable white
      spotting phenotype, for which conventional Sanger sequencing of the candidate
      genes' individual exons had failed to reveal the causative variant. We obtained
      whole genome sequence data from an affected horse and specifically searched for
      structural variants in the known candidate genes. This analysis revealed a
      heterozygous ~1.9-kb deletion spanning exons 10-13 of the KIT gene
      (chr3:77,740,239_77,742,136del1898insTATAT). In continuity with previously named
      equine KIT variants we propose to designate the newly identified deletion variant
      W22. We had access to 21 horses carrying the W22 allele. Four of them were
      compound heterozygous W20/W22 and had a completely white phenotype. Our data
      suggest that W22 represents a true null allele of the KIT gene, whereas the
      previously identified W20 leads to a partial loss of function. These findings
      will enable more precise genetic testing for depigmentation phenotypes in horses.

PMID- 28444913
TI  - Vesicle Origami: Cuboid Phospholipid Vesicles Formed by Template-Free Self
      Assembly.
AB  - Phospholipid liposomes are archetypical self-assembled structures. To minimize
      the surface tension, the vesicles typically are spherical. Deciphering the
      bilayer code, the basic physical interactions between phospholipids would allow
      these molecules to be utilized as building blocks for novel, non-spherical
      structures. A 1,2-diamidophospholipid is presented that self-assembles into a
      cuboid structure. Owing to intermolecular hydrogen bonding, the bilayer membranes
      form an exceptionally tight subgel packing, leading to a maximization of flat
      structural elements and a minimization of any edges. These conditions are
      optimized in the geometrical structure of a cube. Surprisingly, the lateral
      surface pressure in the membrane is only one third of the value typically assumed
      for a bilayer membrane, questioning a long-standing rule-of-thumb.

PMID- 28444914
TI  - Dynamic nuclear polarization studies on deuterated nitroxyl spin probes.
AB  - Detailed dynamic nuclear polarization and electron spin resonance studies were
      carried out for 3-carbamoyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl, 3-carboxy
      2,2,5,5-tetramethyl-pyrrolidine-1-oxyl,3-methoxycarbonyl-2,2,5,5-tetramethy
      pyrolidine-1-oxyl nitroxyl radicals and their corresponding deuterated nitroxyl
      radicals, used in Overhauser-enhanced magnetic resonance imaging for the first
      time. The dynamic nuclear polarization parameters such as dynamic nuclear
      polarization (DNP) factor, longitudinal relaxivity, saturation parameter, leakage
      factor and coupling factor were estimated for deuterated nitroxyl radicals. DNP
      enhancement increases with agent concentration up to 3 mm and decreases above 3
      mm. The proton spin-lattice relaxation time and the longitudinal relaxivity
      parameters were estimated. The leakage factor increases with increasing agent
      concentration up to 3 mm and reaches plateau in the region 3-5 mm. The coupling
      parameter shows the interaction between the electron and nuclear spins to be
      mainly dipolar in origin. DNP spectrum exhibits that the full width at half
      maximum values are higher for undeuterated nitroxyl radicals compared with
      deuterated nitroxyl radicals, which leads to the increase in DNP enhancement. The
      ESR parameters such as, the line width, line shape, signal intensity ratio,
      rotational correlation time, hyperfine coupling constant and g-factor were
      calculated. The narrow line width was observed for deuterated nitroxyl radicals
      compared with undeuterated nitroxyl radicals, which leads to the higher
      saturation parameter value and DNP enhancement. The novelty of the work permits
      clear understanding of the DNP parameters determining the higher DNP enhancement
      compared with the undeuterated nitroxyl radicals. Copyright (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 28444916
TI  - Perfectly Alternating and Regioselective Copolymerization of Carbonyl Sulfide and
      Epoxides by Metal-Free Lewis Pairs.
AB  - The preparation of perfectly alternating and regioslective copolymers derived
      from the copolymerization of carbonyl sulfide (COS) and epoxides by metal-free
      Lewis pair catalysts composed of a Lewis base (amidine, guanidine, or quaternary
      onium salts) and a Lewis acid (triethyl borane) is described. Colorless and
      highly transparent copolymers of poly(monothiocarbonate) were successfully
      obtained with over 99 % tail-to-head content and high molecular weight (up to
      92.5 kg mol-1 ). In most instances, oxygen-sulfur exchange reactions (O/S ERs),
      which would generate random thiocarbonate and carbonate units, were effectively
      suppressed. The turnover frequencies (TOF) of these Lewis pair catalyzed
      processes were as high as 119 h-1 at ambient temperature.

PMID- 28444915
TI  - Hydroquinone induces TK6 cell growth arrest and apoptosis through PARP-1/p53
      regulatory pathway.
AB  - Hydroquinone (HQ), one of the most important metabolites derived from benzene,
      induces cell cycle arrest and apoptosis. Poly(ADP-ribose) polymerase-1 (PARP-1)
      participates in various biological processes, including DNA repair and cell cycle
      regulation. To explore whether PARP-1 regulatory pathway mediated HQ-induced cell
      cycle arrest and apoptosis, we assessed the effect of PARP-1 suppression on
      induction of apoptosis analyzed by FACSCalibur flow cytometer in PARP-1
      deficientTK6 cells (TK6-shPARP-1). We observed an increase in the fraction of
      cells in G1 phase by 7.6% and increased apoptosis by 4.5% in PARP-1-deficient TK6
      cells (TK6-shPARP-1) compared to those negative control cells (TK6-shNC cells) in
      response to HQ treatment. Furthermore, HQ might activate the extrinsic pathways
      of apoptosis via up-regulation of Fas expression, followed by caspase-3
      activation, apoptotic body, and sub G1 accumulation. Enhanced p53 expression was
      observed in TK6-shPARP-1 cells than in TK6-shNC cells after HQ treatment. In
      contrast, Fas expression was lower in TK6-shPARP-1 cells than in TK6-shNC cells.
      Therefore, we conclude that HQ may activate apoptotic signals via Fas up
      regulation and p53-mediated apoptosis in TK6-shNC cells. The reduction of PARP-1
      expression further intensified up-regulation of p53 in TK6-shPARP-1 cells,
      resulting in an increased G1->S phase cell arrest and apoptosis in TK6-shPARP-1
      cells compared to TK6-shNC cells.

PMID- 28444917
TI  - Ultrastructural comparison of the Drosophila larval and adult ventral abdominal
      neuromuscular junction.
AB  - Drosophila melanogaster has recently emerged as model system for studying
      synaptic transmission and plasticity during adulthood, aging and
      neurodegeneration. However, still little is known about the basic neuronal
      mechanisms of synaptic function in the adult fly. Per se, adult Drosophila
      neuromuscular junctions should be highly suited for studying these aspects as
      they allow for genetic manipulations in combination with ultrastructural and
      electrophysiological analyses. Although different neuromuscular junctions of the
      adult fly have been described during the last years, a direct ultrastructural
      comparison with their larval counterpart is lacking. The present study was
      designed to close this gap by providing a detailed ultrastructural comparison of
      the larval and the adult neuromuscular junction of the ventrolongitudinal muscle.
      Assessment of several parameters revealed similarities but also major differences
      in the ultrastructural organisation of the two model neuromuscular junctions.
      While basic morphological parameters are retained from the larval into the adult
      stage, the analysis discovered major differences of potential functional
      relevance in the adult: The electron-dense membrane apposition of the presynaptic
      and postsynaptic membrane is shorter, the subsynaptic reticulum is less
      elaborated and the number of synaptic vesicles at a certain distance of the
      presynaptic membrane is higher.

PMID- 28444918
TI  - Kinetic Resolution of 2-Substituted Indolines by N-Sulfonylation using an
      Atropisomeric 4-DMAP-N-oxide Organocatalyst.
AB  - The first catalytic kinetic resolution by N-sulfonylation is described. 2
      Substituted indolines are resolved (s=2.6-19) using an atropisomeric 4
      dimethylaminopyridine-N-oxide (4-DMAP-N-oxide) organocatalyst. Use of 2-isopropyl
      4-nitrophenylsulfonyl chloride is critical to the stereodiscrimination and
      enables facile deprotection of the sulfonamide products with thioglycolic acid. A
      qualitative model that accounts for the stereodiscrimination is proposed.

PMID- 28444919
TI  - Opportunities and Challenges for Laser Synthesis of Colloids.

PMID- 28444920
TI  - Synthesis of Mono-, Bis- and Tris(pentafluoroethyl)tin Derivatives, (C2 F5 )4-n
      SnXn (X=Ph, Me, Cl, Br, Cp; n=1-3).
AB  - For (pentafluoroethyl)phenylstannanes, (C2 F5 )4-n  SnPhn (n=1-3), and
      dimethylbis(pentafluoroethyl)stannane, (C2 F5 )2 SnMe2 , a high yield synthesis
      was developed by the use of LiC2 F5 as a C2 F5 transfer reagent. The treatment of
      these products with gaseous hydrogen chloride or hydrogen bromide afforded (C2 F5
      )4-n SnXn (X=Cl, Br; n=1-3) in good yields. The (pentafluoroethyl)stannanes were
      fully characterized by 1 H, 13 C, 19 F and 119 Sn NMR, IR spectroscopy and mass
      spectrometry. The treatment of the (pentafluoroethyl)tin halides (C2 F5 )4-n SnXn
      with 1,10-phenanthroline (phen) led to the formation of the corresponding
      octahedrally coordinated complexes [(C2 F5 )4-n SnXn (phen)], the structures of
      which were elucidated by X-ray diffraction analyses. The bromostannane (C2 F5 )3
      SnBr reacted with sodium cyclopentadienide to give the (eta1 
      cyclopentadienyl)tris(pentafluoroethyl)stannane, (C2 F5 )3 SnCp, for which single
      crystal X-ray diffraction analysis could be performed. The coupling constants 1
      J(119 Sn,13 C) and 2 J(119 Sn,19 F) of all new stannanes are strongly correlated
      and sensitive to the substitution pattern at the tin atom. For both coupling
      constants a negative sign could be assigned.

PMID- 28444921
TI  - Biochemical Characterization and Analyses of Polysialic-Acid-Associated Carrier
      Proteins and Genes in Piglets during Neonatal Development.
AB  - Polysialic acid plays a key role in cancer metastasis and neurodevelopment. Our
      aim was to determine the developmental gene-expression profiles for the two
      polysialyltransferases ST8Sia II and ST8Sia IV, neural cell-adhesion molecules
      (NCAMs), SynCAM 1, neuropilin-2 (NRP2) and their polysialylated cognate glycans
      in different regions of the piglet brain during postnatal development. Our
      findings show that: 1) the cellular levels of mRNA coding for ST8Sia II and
      ST8Sia IV, NCAMs, SynCAM 1, NRP2 and polySia are age-dependent and cell-type
      specific during neonatal brain development, 2) there was a lack of correlation
      between abundance level of mRNA coding for ST8Sia II and ST8Sia IV and the
      abundance level of the post-translation expression of polySia in all nine brain
      regions, 3) expression levels of polySia did not correlate with the levels of the
      carrier proteins NCAM-140, SynCAM 1 and NRP2 in nine brain regions, and 4) the
      cellular abundance of ST8Sia II and ST8Sia IV in nine subregions of piglet brain
      is regulated at the level of translation/post-translation, and not at the level
      of transcription. Collectively, our findings suggest that neuronal and glial
      cells within different regions of the brain have different transcriptional
      programs that can direct cell division at different rates based on the activity
      levels of ST8Sia II and ST8Sia IV and the level of their carrier proteins during
      neurodevelopment.

PMID- 28444922
TI  - Regulation of organelle function by metformin.
AB  - Metformin ameliorates hyperglycemia without the side effects of lactic acidosis
      or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic
      glucose production in the liver and by increasing glucose uptake in the muscle.
      Recent studies show that metformin induces cell death in certain cancer cell
      lines by interfering with the metabolism of the cancer cells. Therefore,
      understanding the mechanisms of action for metformin will provide insights into
      how to better treat diabetes and other metabolic disorders and also into the
      development of new therapeutic drugs. One of the best understood molecular
      targets of metformin is the mitochondrial complex I. However, given metformin's
      broad effects on metabolism, it could act on multiple targets. In this review, we
      summarize current findings in metformin's mechanisms of action regarding its
      known targets in mitochondria and known effects in cancer cell lines. Then, we
      introduce endosomal Na+ /H+ exchangers and the V-ATPase as new potential targets
      of metformin's action. Finally, we will discuss the hypothesis that metformin
      directly acts on endosome/lysosome regulation so as to regulate metabolism and
      ultimately alleviate type 2 diabetes. (c) 2017 IUBMB Life, 69(7):459-469, 2017.

PMID- 28444924
TI  - Corrigendum.

PMID- 28444923
TI  - Anaerobic Respiration on Self-Doped Conjugated Polyelectrolytes: Impact of
      Chemical Structure.
AB  - We probe anaerobic respiration of bacteria in the presence of conjugated
      polyelectrolytes (CPEs). Three different CPEs were used to probe how structural
      variations impact biocurrent generation from Shewanella oneidensis MR-1. For the
      self-doped anionic CPE only, absorption spectroscopy shows that the addition of
      S. oneidensis MR-1 leads to the disappearance of the polaron (radical cation)
      band at >900 nm and an increase in the band at 735 nm due to the neutral species,
      consistent with electron transfer from microbe to polymer. Microbial three
      electrode electrochemical cells (M3Cs) show an increase in the current generated
      by S. oneidensis MR-1 with addition of the self-doped CPE relative to other CPEs
      and controls. These experiments combined with in situ cyclic voltammetry suggest
      that the doped CPE facilitates electron transport to electrodes and reveal
      structure-function relationships relevant to developing materials for
      biotic/abiotic interfaces.

PMID- 28444925
TI  - Highly Efficient Carbon Monoxide Capture by Carbanion-Functionalized Ionic
      Liquids through C-Site Interactions.
AB  - A novel method for the highly efficient and reversible capture of CO in carbanion
      functionalized ionic liquids (ILs) by a C-site interaction is reported. Because
      of its supernucleophilicity, the carbanion in ILs could absorb CO efficiently. As
      a result, a relatively high absorption capacity for CO (up to 0.046 mol mol-1 )
      was achieved under ambient conditions, compared with CO solubility in a commonly
      used IL [Bmim][Tf2 N] (2*10-3  mol mol-1 ). The results of quantum mechanical
      calculations and spectroscopic investigation confirmed that the chemical
      interaction between the C-site in the carbanion and CO resulted in the superior
      CO absorption capacities. Furthermore, the subsequent conversion of captured CO
      into valuable chemicals with good reactivity was also realized through the
      alkoxycarbonylation reaction under mild conditions. Highly efficient CO
      absorption by carbanion-functionalized ILs provides a new way of separating and
      converting CO.

PMID- 28444926
TI  - Which blood pressure measurement, systolic or diastolic, better predicts future
      hypertension in normotensive young adults?
AB  - The impact of age-related differences in blood pressure (BP) components on new
      onset hypertension is not known. A follow-up examination of 93 303 normotensive
      individuals (mean age 41.1 years) who underwent a health checkup in 2005 was
      conducted every year for 8 years. The primary end point was new-onset
      hypertension (systolic BP [SBP]/diastolic BP [DBP] >=140/90 mm Hg and/or the
      initiation of antihypertensive medications with self-reported hypertension).
      During the mean 4.9 years of follow-up, 14 590 subjects developed hypertension.
      The impact of DBP on the risk of developing hypertension compared with optimal BP
      (SBP <120 mm Hg and DBP <80 mm Hg) was significantly greater than that of SBP in
      subjects younger than 50 years (hazard ratios, 17.5 for isolated diastolic high
      normal vs 10.5 for isolated systolic high-normal [P<.001]; 8.0 for isolated
      diastolic normal vs 4.1 for isolated systolic normal [P<.001]). Among the
      subjects 50 years and older, the corresponding effects of DBP and SBP were
      similar. Regarding the risk of new-onset hypertension, high DBP is more important
      than SBP in younger adults (<50 years) with normal or high-normal BP.

PMID- 28444927
TI  - Endo-alpha-Mannosidase-Catalyzed Transglycosylation.
AB  - In order for facilitating the synthesis of oligosaccharides, transglycosylation
      reactions mediated by glycoside hydrolases have been studied in various contexts.
      In this study, we examined the transglycosylating activity of a Golgi endo-alpha
      mannosidase. We prepared various glycosyl donors and acceptors, and recombinant
      human Golgi endo-alpha-mannosidase and its various mutants were expressed. The
      enzyme was able to mediate transglycosylation from alpha-glycosyl-fluorides.
      Systematic screening of various point mutants revealed that the E407D mutant had
      excellent transglycosylation activity and extremely low hydrolytic activity.
      Substrate specificity analysis revealed that minimum motif required for glycosyl
      acceptor is Manalpha1- 2Man. The synthetic utility of the enzyme was demonstrated
      by generation of a high-mannose-type undecasaccharide (Glc1 Man9 GlcNAc2 ).

PMID- 28444928
TI  - Antiinflammatory Activity of Cinnamon (Cinnamomum zeylanicum) Bark Essential Oil
      in a Human Skin Disease Model.
AB  - The effect of cinnamon (Cinnamomum zeylanicum) bark essential oil (CBEO) on human
      skin cells has not been elucidated. Therefore, we investigated the activity of a
      commercially available CBEO in a validated human dermal fibroblast system, a
      model of chronic inflammation and fibrosis. We first evaluated the impact of CBEO
      on 17 protein biomarkers that play critical roles in inflammation and tissue
      remodeling. The impact of CBEO on genome-wide gene expression was also evaluated.
      CBEO showed strong anti-proliferative effects on skin cells and significantly
      inhibited the production of several inflammatory biomarkers, including vascular
      cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte
      chemoattractant protein-1, interferon gamma-induced protein 10, interferon
      inducible T-cell alpha chemoattractant, and monokine induced by gamma interferon.
      In addition, CBEO significantly inhibited the production of several tissue
      remodeling molecules, including epidermal growth factor receptor, matrix
      metalloproteinase-1, and plasminogen activator inhibitor-1. Macrophage colony
      stimulating factor, which is an immunomodulatory protein molecule, was also
      significantly inhibited by CBEO. Furthermore, CBEO significantly modulated global
      gene expression and altered signaling pathways, many of which are important in
      inflammation, tissue remodeling, and cancer biology. The study shows that CBEO is
      a promising antiinflammatory agent; however, further research is required to
      clarify its clinical efficacy. (c) 2017 The Authors. Phytotherapy Research
      published by John Wiley & Sons Ltd.

PMID- 28444929
TI  - Antiretinal antibodies in central serous chorioretinopathy: prevalence and
      clinical implications.
AB  - PURPOSE: To investigate the possible role of autoimmune reactions directed
      against retinal tissue in central serous chorioretinopathy (CSC), by analysing
      the presence of serum antiretinal antibodies (ARAs) and establishing their
      clinical relevance. METHODS: Sixty-three patients with CSC were included, and
      clinical characteristics were collected. Serum samples of all patients with CSC,
      101 uveitis patients and 60 healthy donors were analysed for the presence of ARAs
      by indirect immunofluorescence. Furthermore, all CSC serum samples were analysed
      on Western blot. Correlations between laboratory findings and clinical features
      of CSC were determined by logistic regression. RESULTS: Antiretinal antibodies
      (ARAs) were present in 54% of the patients with CSC, in 46% of uveitis patients
      (p = 0.153) and in 17% of healthy controls (p < 0.001). The majority of ARAs in
      CSC were directed against photoreceptors (27%), which occurred significantly more
      often compared to uveitis patients (15%, p = 0.039) and to healthy controls (5%,
      p = 0.003). No associations between clinical CSC characteristics and the presence
      of ARAs were found. CONCLUSION: Serum ARAs are present in more than half of the
      patients with CSC, and especially, ARAs directed against photoreceptors were
      detected more frequently compared to both healthy controls and uveitis patients.
      Further research is warranted to unravel the role of ARAs in the pathogenesis of
      CSC.

PMID- 28444930
TI  - Does postexercise modelled capillary blood flow accurately reflect cardiovascular
      effects by different exercise intensities?
AB  - Blood flow (BF) in exercising muscles is an important factor for exercise
      capacity. Recently, a non-invasive method to estimate capillary BF (Qcap ) was
      introduced. Using this method, the Fick principle is re-arranged by using
      relative differences in deoxygenated haemoglobin (DeltaHHb) as a surrogate for
      arteriovenous O2 difference and pulmonary oxygen uptake (VO2 ) instead of
      muscular oxygen uptake. The aim of this study was to examine (I) the relationship
      between Qcap and exercise intensity during and following exercise, and (II) to
      critically reflect the Qcap approach. Seventeen male subjects completed six bouts
      of cycling exercise with different exercise intensities (40-90% peak oxygen
      uptake, VO2peak ) in randomized order. VO2 and DeltaHHb were monitored
      continuously during the trail. Qcap was modelled bi-exponentially, and mean
      response time (MRT) was calculated during recovery as well as the dissociation of
      modelled VO2 and Qcap recovery kinetics (MRT/tauVO2 ). End-exercise Qcap
      increased continuously with exercise intensity. This also applied to MRT.
      Postexercise MRT/tauVO2 increased from 40 to 60% VO2peak but remained stable
      thereafter. The results show that Qcap response to exercise is linearly related
      to exercise intensity. This is presumably due to vasoactive factors like shear
      stress or endothelial-mediated vasodilation. MRT/tauVO2 shows that postexercise
      Qcap is elevated for a longer period than VO2 , which is representative for
      metabolic demand following exercise >=70% VO2peak . This is a hint for prolonged
      local vasodilation. According to previous studies, Qcap could not be modelled
      properly in some cases, which is a limitation to the method and therefore has to
      be interpreted with caution.

PMID- 28444931
TI  - Study of structure-dependent chromatographic behavior of glycopeptides using
      reversed phase nanoLC.
AB  - Analysis of glycosylation is challenging due to micro- and macro-heterogeneity of
      the protein attachment. A combination of LC with MS/MS is one of the most
      powerful tools for glycopeptide analysis. In this work, we show the effect of
      various monosaccharide units on the retention time of glycopeptides. Retention
      behavior of several glycoforms of six peptides obtained from tryptic digest of
      haptoglobin, hemopexin, and sex hormone-binding globulin was studied on a
      reversed phase chromatographic column. We observed reduction of the retention
      time with increasing number of monosaccharide units of glycans attached to the
      same peptide backbone. Fucosylation of larger glycans provides less significant
      retention time shift than for smaller ones. Retention times of glycopeptides were
      expressed as relative retention times. These relative retention times were used
      for calculation of upper and lower limits of glycopeptide retention time windows
      under the reversed phase conditions. We then demonstrated on the case of a
      glycopeptide of haptoglobin that the predicted retention time window boosts
      confidence of identification and minimizes false-positive identification.
      Relative retention time, as a qualitative parameter, is expected to improve LC
      MS/MS characterization of glycopeptides.

PMID- 28444932
TI  - The association of LAMB1 polymorphism and expression changes with the risk of
      coal workers' pneumoconiosis.
AB  - BACKGROUND: Pneumoconiosis is a serious occupational disease worldwide, which is
      characterized by irreversible and diffuse lung fibrotic lesions. Laminin beta
      1(LAMB1) is widely expressed in tissues and it is crucial for both lung
      morphogenesis and physiological function. In this study, we explored the
      association between LAMB1 rs4320486 and risk of pneumoconiosis in a Chinese
      population, as well as its mechanisms. METHODS: In this case-control study, 600
      CWP patients and 605 controls were genotyped for the LAMB1 rs4320486 polymorphism
      using TaqMan methods. Luciferase reporter assay was used to assess the LAMB1
      transcriptional activities. The protein levels in cells and tissues were detected
      by western blot, and mRNA levels were determined by qRT-PCR. RESULTS: Logistic
      regression analysis revealed that individuals with LAMB1 rs4320486 CT/TT
      genotypes had a significantly decreased risk of CWP (adjusted OR = 0.78, 95%CI =
      0.64-0.94), compared with individuals with CC genotypes. Luciferase assays showed
      that the LAMB1 rs4320486(C > T) substitution could decrease the expression of
      LAMB1. Compared with normal groups, mRNA levels of LAMB1 were up-regulated in
      lung tissues of patients with pulmonary fibrosis. Additionally, expressions of
      LAMB1 and alpha-SMA were enhanced progressively, along with the development of
      lung fibrosis, while E-cadherin decreased. CONCLUSIONS: In this study, the
      functional LAMB1 rs4320486 mutation was associated with a decreased risk of CWP
      in a Chinese population, probably owing to the reduced activity of LAMB1
      transcription. LAMB1 expression was increased in the progress of lung fibrosis,
      which suggests that LAMB1 may affect the initiation and progression of
      pneumoconiosis, or serve as a potential biomarker of pneumoconiosis for diagnosis
      and genetic susceptibility.

PMID- 28444933
TI  - Synergistic effect of carbon nuclei and polyaromatic hydrocarbons on respiratory
      and immune responses.
AB  - Particulate matter with aerodynamic diameter <=2.5 MUm (PM2.5 ) is generally
      composed of carbon nuclei associated with various organic carbons, metals, ions
      and biological materials. Among these components, polyaromatic hydrocarbons
      (PAHs) such as benzo(a)pyrene (BaP) and quinones have detrimental effects on
      airway epithelial cells and immunodisrupting effects, which leads to the
      exacerbation of respiratory allergies. The effects of PAHs and the carbon nuclei,
      separately as well as in combination, remain to be established. We investigated
      the effects of BaP, 9,10-phenanthroquinone (9,10-PQ), and 1,2-napthoquinone (1,2
      NQ) and their combined effects with heated diesel exhaust particle (H-DEP) as
      carbon nuclei of typical PM2.5 . We exposed human airway epithelial cells (BEAS
      2B), murine bone marrow-derived antigen-presenting cells (APCs), and murine
      splenocytes to BaP, 9,10-PQ, or 1,2-NQ in the presence and absence of H-DEP.
      Several important inflammatory cytokines and cell surface molecules were
      measured. PAHs alone did not have apparent cytotoxic effects on BEAS-2B, whereas
      combined exposure with H-DEP induced noticeable detrimental effects which mainly
      reflected the action of H-DEP itself. BaP increased CD86 expression as an APC
      surface molecule regardless of the presence or absence of H-DEP. None of the BaP,
      9,10-PQ, or 1,2-NQ exposure alone or their combined exposure with H-DEP resulted
      in any significant activation of splenocytes. These results suggest that PAHs and
      carbon nuclei show additive effects, and that BaP with the carbon nuclei may
      contribute to exacerbations of allergic respiratory diseases including asthma by
      PM2.5 , especially via antigen-presenting cell activation.

PMID- 28444934
TI  - Dynamic Iminoboronate-Based Boroxine Chemistry for the Design of Ambient Humidity
      Sensitive Self-Healing Polymers.
AB  - Developing intrinsic self-healing polymeric materials is of great interest
      nowadays to extend material lifetime and/or prevent the replacement of damaged
      pieces. Spontaneously humidity-sensitive healable polymer network built around
      dynamic covalent B-O bonds was templated by using iminoboronate-based boroxine
      derivatives. Taking advantage of the dynamic boroxine/boronic acid equilibrium
      and iminoboronate chemistry, it is possible to construct polymeric materials able
      to self-heal without requiring any energy-demanding external activation.
      Interestingly, this novel family of iminoboronate adduct-based materials can be
      readily produced by a relatively simple and straightforward synthesis between
      boronic acid and diamine-based compounds, paving the way to coatings that are
      self-healable at ambient humidity.

PMID- 28444935
TI  - Hydration status influences the measurement of arterial stiffness.
AB  - Consensus guidelines have attempted to standardize the measurement and
      interpretation of pulse wave velocity (PWV); however, guidelines have not
      addressed whether hydration status affects PWV. Moreover, multiple studies have
      utilized heat stress to reduce arterial stiffness which may lead to dehydration.
      This study utilized two experiments to investigate the effects of dehydration on
      PWV at rest and during passive heat stress. In experiment 1, subjects (n = 19)
      completed two trials, one in which they arrived euhydrated and one dehydrated
      (1.2[1.0]% body mass loss). In experiment 2, subjects (n = 11) began two trials
      euhydrated and in one trial did not receive water during heat stress, thus
      becoming dehydrated (1.6[0.6]% body mass loss); the other trial subjects remained
      euhydrated. Using Doppler ultrasound, carotid-to-femoral (central) and carotid-to
      radial (peripheral) PWVs were measured. PWV was obtained at a normothermic
      baseline, and at a 0.5 degrees C and 1 degrees C elevation in rectal temperature
      (via passive heating). In experiment 1, baseline central PWV was significantly
      higher when euhydrated compared to dehydrated (628[95] versus 572[91] cm s-1 ,
      respectively; P<0.05), but peripheral PWV was unaffected (861[117] versus
      825[149] cm s-1 ; P>0.05). However, starting euhydrated and becoming dehydrated
      during heating in experiment 2 did not affect PWV measures (P>0.05), and
      independent of hydration status peripheral PWV was reduced when rectal
      temperature was elevated 0.5 degrees C (-74[45] cm s-1 ; P<0.05) and 1.0 degrees
      C (-70[48] cm s-1 ; P<0.05). Overall, these data suggest that hydration status
      affects measurements of central PWV in normothermic, resting conditions.
      Therefore, future guidelines should suggest that investigators ensure adequate
      hydration status prior to measures of PWV.

PMID- 28444937
TI  - Soluble Porous Coordination Frameworks Constructed from Inorganic Nanoparticles
      as Homogenized Heterogeneous Photocatalysts for Suzuki Coupling Reactions under
      Near-Infrared Light.
AB  - Self-assembly has emerged as a promising method to control the structure and
      properties of ensembles of inorganic nanoparticles (NPs) for exploiting their
      collective effects. However, the rational assembly of inorganic NPs into soluble
      porous architectures for use as homogenized heterogeneous catalysts has been less
      studied. Herein, it is shown that inorganic NPs can be used for the assembly of
      soluble porous coordination frameworks (PCFs) by atom-scale interfacial
      coordination-driven assembly. Owing to their large pore size, high dispersity in
      solution, strong absorption in the near-infrared (NIR) range, and long-lived
      electron-hole pair, the obtained soluble frameworks could serve as a platform for
      homogenized heterogeneous photocatalysts, which exhibited excellent activity,
      high apparent quantum efficiency, and recyclability in the catalysis of the noble
      metal-free Suzuki coupling reactions under NIR light at room temperature.
      Moreover, PCF catalysts can be reused more than five times without significant
      loss of activity, which indicates long-term stability. The present strategy to
      fabricate soluble porous nanostructures opens a new chemical toolbox for
      homogenized heterogeneous catalysts and may bring new inspiration to
      photocatalysis.

PMID- 28444936
TI  - Blood flow restriction attenuates eccentric exercise-induced muscle damage
      without perceptual and cardiovascular overload.
AB  - The aim of this study was to evaluate the acute effects of high-intensity
      eccentric exercise (HI-ECC) combined with blood flow restriction (BFR) on muscle
      damage markers, and perceptual and cardiovascular responses. Nine healthy men (26
      +/- 1 years, BMI 24 +/- 1 kg m- 2) underwent unilateral elbow extension in two
      conditions: without (HI-ECC) and with BFR (HI-ECC+BFR). The HI-ECC protocol
      corresponded to three sets of 10 repetitions with 130% of maximal strength (1RM).
      The ratings of perceived exertion (RPE) and pain (RPP) were measured after each
      set. Muscle damage was evaluated by range of motion (ROM), upper arm
      circumference (CIR) and muscle soreness using a visual analogue scale at
      different moments (pre-exercise, immediately after, 24 and 48 h postexercise).
      Systolic (SBP), diastolic (DBP), mean blood pressure (MBP) and heart rate (HR)
      were measured before exercise and after each set. RPP was higher in HI-ECC+BFR
      than in HI-ECC after each set. Range of motion decreased postexercise in both
      conditions; however, in HI-ECC+BFR group, it returned to pre-exercise condition
      earlier (post-24 h) than HI-ECC (post-48 h). CIR increased only in HI-ECC, while
      no difference was observed in HI-ECC+BFR condition. Regarding cardiovascular
      responses, MBP and SBP did not change at any moment. HR showed similar increases
      in both conditions during exercise while DBP decreased only in HI-ECC condition.
      Thus, BFR attenuated HI-ECC-induced muscle damage and there was no increase in
      cardiovascular responses.

PMID- 28444938
TI  - Low concentration arsenite activated JAK2/STAT3 signal and increased
      proliferative factor expressions in SV-HUC-1cells after short and long time
      treatment.
AB  - Epidemiological studies have indicated that ingestion of inorganic arsenic
      resulted in increased risks of bladder cancer and chronic hyperproliferation
      could play a direct role in the development of cancer. This study examined the
      effects of arsenite on JAK2/STAT3 pathway and expressions of proliferation and
      anti-apoptosis factors. The results showed that long term exposure to low doses
      arsenite enhanced human uroepithelial cells (SV-HUC-1 cells) proliferation and
      BrdU positive rate was significant increased. mRNA and protein expressions of
      proliferation factors, such as cyclin D1, COX-2, and proliferating cell nuclear
      antigen (PCNA), increased in chronically exposed arsenite SV-HUC-1 cells with
      exposure time. Furthermore, JAK2/STAT3 signal pathway was activated following
      exposure to arsenite in SV-HUC-1 cells. Knockdown of STAT3 reduced expressions of
      cyclin D1, COX-2, PCNA, and BCL2 induced by arsenite. In conclusion, arsenic
      induced proliferation in human uroepithelial cells after short and long term
      exposure to arsenite and JAK2/STAT3 signaling pathway might be pivotal in
      arsenite-induced proliferation by regulating cyclin D1, COX-2, PCNA, and BCL2.

PMID- 28444939
TI  - Continuous ambulatory peritoneal dialysis, ascitic and pleural body fluids
      evaluation with the Mindray BC-6800 hematology analyzer.
AB  - BACKGROUND: Accurate evaluation of hematology analyzers is recommended before
      these devices can be broadly introduced for the routine testing of continuous
      ambulatory peritoneal dialysis (CAPD), ascitic, and pleural fluids. METHODS: We
      evaluated the performance of Mindray BC-6800 for white blood cell (WBC) and
      differential cell count in 50 CAPD, 60 ascitic and 40 pleural compared with
      manual microscopy. Within-run precision, limit of blank (LoB), limit of detection
      (LoD), limit of quantitation (LoQ), and carryover were assessed. RESULTS: The
      Passing-Bablok regression in all fluids showed the following equations: yWBC
      =1.05x+3.31 (95%CI slope 0.95 to 1.12; intercept -0.25 to 5.52); yMN =0.85x+15.63
      (95%CI slope 0.72 to 1.05; intercept -24.18 to 84.47); and yPMN =1.21x+13.37
      (95%CI slope 1.03 to 1.35; intercept 4.00 to 32.47) with bias 78 cells/MUL. The
      AUC for clinical PMN cut-off was 0.88 (95%CI: 0.77 to 0.98). In ascitic, pleural,
      and CAPD fluids the AUC for clinical PMN cut-off were 0.88 (95%CI: 0.63 to 1.00),
      0.83 (95%CI: 0.68 to 0.99), and 1.00 (95%CI: 1.00 to 1.00) respectively. CV
      ranged from 3%-34%. LoB of 3 cell/MUL was verified. LoD and LoQ reported the same
      result (8 cells/MUL). Carry over never exceeded 0.05%. CONCLUSION: The
      effectiveness of BC-6800 to categorize cells from different body fluids was not
      compromised by the slight positive bias observed. This conclusion is supported by
      the high AUC and agreement between the automated method and the reference method.
      The results show that BC-6800 offers rapid, accurate, and reproducible results
      for clinical management of CAPD, ascitic, and pleural fluids.

PMID- 28444940
TI  - H-reflex and M-wave recordings: effect of pressure application to the stimulation
      electrode on the assessment of evoked potentials and subject's discomfort.
AB  - This study aimed to compare the effect of different types of pressure applied to
      the stimulation electrode on assessing the efficiency of Ia-alpha-motoneuron
      transmission of the soleus muscle and the associated discomfort using electrical
      nerve stimulation. Twelve healthy young adults participated in three experimental
      sessions (one for each knee angle). The amplitudes of the maximal Hoffmann reflex
      (Hmax ) and motor potential (Mmax ) were recorded from the soleus muscle at 0
      degrees , 30 degrees  and 90 degrees  knee angles (0 degrees  full extension)
      through three pressure applications to the stimulation electrode: no pressure,
      pressure with manual application and pressure using adhesive tape. The soleus
      Hmax /Mmax were calculated to assess the efficiency of Ia-alpha-motoneuron
      transmission during varied knee angles and pressure application to the
      stimulation electrode. At the stimulation intensity evoking soleus Hmax and Mmax
      , subjects were asked to orally provide a value between 'no discomfort' (0) and
      'worst possible discomfort' (10). The application of pressure on the stimulation
      electrode, particularly using adhesive tape, decreased both the stimulation
      intensity needed to evoke an electrophysiological response and the associated
      self-reported discomfort (P<0.05), while the Hmax /Mmax remained constant. At the
      stimulation intensity evoking Mmax , the electrical stimulation appeared to be
      more painful at 0 degrees  knee angle compared with 30 degrees  and 90 degrees 
      angles (P<0.01). To conclude, this study showed that a knee flexion and a
      pressure application to the stimulation electrode, especially using tape
      pressure, are recommended in the objective to reduce the patient/subjects'
      discomfort when eliciting evoked potentials on soleus muscle.

PMID- 28444942
TI  - Combined inhibition of autophagy protein 5 and galectin-1 by thiodigalactoside
      reduces diet-induced obesity through induction of white fat browning.
AB  - Our previous study demonstrated that thiodigalactoside (TDG) ameliorates obesity
      by targeted inhibition of galectin-1 (GAL1). Here, for the first time, we report
      the unexpected role of GAL1 and ATG5 inhibition by TDG in lipid metabolism. Core
      thermogenic marker proteins and genes were highly induced in white adipose tissue
      (WAT) of rats fed a high fat diet (HFD) and TDG, resulting in the significant
      development of brown fat-like adipocytes in inguinal WAT. TDG treatment reduced
      weight gain and fat mass as well as activated brown adipose tissue (BAT) in HFD
      fed rats. TDG also reduced protein levels of LC3-II and increased protein levels
      of P62, suggesting its possible role in suppression of autophagy. Combined
      inhibition of GAL1 and ATG5 by TDG treatment protected rats against both HFD
      induced adipogenesis as well as lipogenesis, as evidenced by suppression of
      CCAAT/enhancer-binding protein alpha, peroxisome proliferator-activated receptor
      gamma and fatty acid synthase. In conclusion, the present findings suggest that
      TDG plays a role in browning and lipid catabolism by combined inhibition of GAL1
      and ATG5 and thus may have potential therapeutic implications in the regulation
      of energy homeostasis via its action in WAT. (c) 2017 IUBMB Life, 69(7):510-521,
      2017.

PMID- 28444941
TI  - Automated ultrasound edge-tracking software comparable to established semi
      automated reference software for carotid intima-media thickness analysis.
AB  - Many commercial ultrasound systems are now including automated analysis packages
      for the determination of carotid intima-media thickness (cIMT); however, details
      regarding their algorithms and methodology are not published. Few studies have
      compared their accuracy and reliability with previously established automated
      software, and those that have were in asymptomatic adults. Therefore, this study
      compared cIMT measures from a fully automated ultrasound edge-tracking software
      (EchoPAC PC, Version 110.0.2; GE Medical Systems, Horten, Norway) to an
      established semi-automated reference software (Artery Measurement System (AMS)
      II, Version 1.141; Gothenburg, Sweden) in 30 healthy preschool children (ages 3-5
      years) and 27 adults with coronary artery disease (CAD; ages 48-81 years). For
      both groups, Bland-Altman plots revealed good agreement with a negligible mean
      cIMT difference of -0.03 mm. Software differences were statistically, but not
      clinically, significant for preschool images (P = 0.001) and were not significant
      for CAD images (P = 0.09). Intra- and interoperator repeatability was high and
      comparable between software for preschool images (ICC, 0.90-0.96; CV, 1.3-2.5%),
      but slightly higher with the automated ultrasound than the semi-automated
      reference software for CAD images (ICC, 0.98-0.99; CV, 1.4-2.0% versus ICC, 0.84
      0.89; CV, 5.6-6.8%). These findings suggest that the automated ultrasound
      software produces valid cIMT values in healthy preschool children and adults with
      CAD. Automated ultrasound software may be useful for ensuring consistency among
      multisite research initiatives or large cohort studies involving repeated cIMT
      measures, particularly in adults with documented CAD.

PMID- 28444943
TI  - Redundancy in the Headache Literature. What Constitutes Unethical Practice.

PMID- 28444944
TI  - Olfactory Modifications in a Migraine Patient With Anosmia.

PMID- 28444945
TI  - Statement of Concern.

PMID- 28444947
TI  - Roosevelt's Headache.

PMID- 28444946
TI  - A Review of Radiofrequency for Arteriovenous Malformations and the Impact on
      Headache.

PMID- 28444948
TI  - Medication Overuse Headache.

PMID- 28444949
TI  - Voxel-based morphometry meta-analysis of gray and white matter finds significant
      areas of differences in bipolar patients from healthy controls.
AB  - OBJECTIVE: We present a retrospective meta-analysis of voxel-based morphometry
      (VBM) of gray (GM) and white matter (WM) differences between patients with
      bipolar disorder (BD) and behaviorally healthy controls. METHODS: We used the
      activation likelihood estimation and Sleuth software for our meta-analysis,
      considering P-value maps at the cluster level inference of .05 with uncorrected
      P<.001. Results were visualized with the software MANGO. RESULTS: We included
      twenty-five articles in the analysis, and separated the comparisons where BD
      patients had lower GM or WM concentrations than controls (573 subjects, 21
      experiments, and 117 locations/180 subjects, five experiments, and 15 locations,
      respectively) and the comparisons where BD patients had greater GM concentrations
      than controls (217 subjects, nine experiments, and 49 locations). Higher WM
      concentrations in BD patients were not detected. We observed for BD reduced GM
      concentrations in the left medial frontal gyrus and right inferior/precentral
      gyri encompassing the insular cortex, and greater GM concentrations in the left
      putamen. Further, lower WM concentrations were detected in the left inferior
      longitudinal fasciculus, left superior corona radiata, and left posterior
      cingulum. CONCLUSIONS: This meta-analysis confirms deterioration of frontal and
      insular regions as already found in previous meta-analysis. GM reductions in
      these regions could be related to emotional processing and decision making, which
      are typically impaired in BD. Moreover, we found abnormalities in precentral
      frontal areas and putamen that have been linked to more basic functions, which
      could point to sensory and specific cognitive deficits. Finally, WM reductions
      involved circuitry that may contribute to emotional dysregulation in BD.

PMID- 28444950
TI  - Optical coherence tomography evaluation of patients with macula-off retinal
      detachment after different postoperative posturing: a randomized pilot study.
AB  - PURPOSE: To assess the presence of outer and inner retinal folds (RFs) and drop
      out of the ellipsoid zone (EZ) occurring after surgical repair of macula-off
      rhegmatogenous retinal detachment (RRD) with different postoperative posture and
      preoperative use of adjuvant perfluorocarbon liquid (PFCO). METHODS: In this
      prospective study, 56 eyes of 56 consecutive patients affected by RRD were
      subjected to 23- or 25-gauge pars plana vitrectomy (PPV). The patients were
      randomized in four groups (14 prone 5 hr without PFCO, 14 supine 5 hr without
      PFCO, 14 prone 5 hr with PFCO and 14 supine 5 hr with PFCO) and followed up with
      spectral domain optical coherence tomography (SD-OCT). RESULTS: Spectral domain
      optical coherence tomography (SD-OCT) was recorded before surgery, at days 30 and
      90 to detect the presence of outer RFs, inner RFs and drop-out of EZ and to
      follow their variation over time. No statistical significance was found in our
      groups for outer RFs, inner RFs, drop-out of EZ formation and evolution. The
      postoperative best-corrected visual acuity (BCVA) improved in all groups (mean
      preoperative BCVA 1.47 logMar +/- 0.19, mean postoperative BCVA 0.27 logMar +/-
      0.11, p < 0.01), without statistical variations between the four groups in BCVA
      after surgery. CONCLUSION: The use of adjuvant and variation in postoperative
      position did not change the risk of presenting outer RFs, inner RFs and drop-out
      of EZ after RRD.

PMID- 28444951
TI  - Alitretinoin therapy for palmoplantar pustulosis.

PMID- 28444952
TI  - Similarity in volatile communities leads to increased herbivory and greater
      tropical forest diversity.
AB  - A longstanding paradigm in ecology is that there are positive associations
      between herbivore diversity, specialization, and plant species diversity, with a
      focus on taxonomic diversity. However, phytochemical diversity is also an
      informative metric, as insect herbivores interact with host plants not as
      taxonomic entities, but as sources of nutrients, primary metabolites, and
      mixtures of attractant and repellant chemicals. The present research examines
      herbivore responses to phytochemical diversity measured as volatile similarity in
      the tropical genus Piper. We quantified associations between naturally occurring
      volatile variation and herbivory by specialist and generalist insects.
      Intraspecific similarity of volatile compounds across individuals was associated
      with greater overall herbivory. A structural equation model supported the
      hypothesis that plot level volatile similarity caused greater herbivory by
      generalists, but not specialists, which led to increased understory plant
      richness. These results demonstrate that using volatiles as a functional
      diversity metric is informative for understanding tropical forest diversity and
      indicate that generalist herbivores contribute to the maintenance of diversity.

PMID- 28444953
TI  - Birth decade affects the sensitization pattern and asthma risk in Finnish adult
      population.
AB  - We have previously shown that sensitizations to several types of allergens
      distinguish subjects with and without adult-onset asthma in Finland. The aim was
      to analyze how age affects sensitization and asthma risk. We used previous
      population-based case-control data (N=456) from Finnish adult asthma patients
      with one or two matched controls. Asthma was diagnosed based on a typical history
      of asthmatic symptoms and lung function tests. Allergic sensitization was
      determined by skin prick test (SPT) to 17 aeroallergens. Information on
      demographics was obtained by a questionnaire. Sensitization to more than one
      allergen type and the number of positive SPT reactions associated with younger
      age and asthma. Atopic subjects aged 65 and above were characterized by
      sensitization to only one to two allergens, with very few animal danders and
      without an association with asthma. Multiple sensitizations and animal dander
      sensitization are more common among Finnish asthmatic adults aged under 56 than
      among older asthmatics. Cohort studies are needed to understand timing of host
      environmental interactions behind this.

PMID- 28444954
TI  - Clinical presentation and outcome of children with central diabetes insipidus
      associated with a self-limited or transient pituitary stalk thickening, diagnosed
      as infundibuloneurohypophysitis.
AB  - OBJECTIVE: Despite lymphocytic or autoimmune infundibuloneurohypophysitis (INH)
      is an increasingly recognized aetiology in children with central diabetes
      insipidus (CDI); clinical data on epidemiology (clinical evolution, predisposing
      factors, complications), diagnosis and management of this entity are limited and
      mostly based on published case reports. The aim of this study was to gain a
      broader insight in the natural history of this disease by analysing the clinical
      presentation, radiological pituitary stalk changes, associated autoimmunity and
      hormonal deficiencies in children with CDI and a self-limiting or transient stalk
      thickening (ST), diagnosed as autoimmune infundibuloneurohypophysitis, during the
      last 15 years in four Belgian university hospitals. DESIGN AND PATIENTS: The
      medical files of nine CDI patients with a ST at initial presentation and no signs
      of Langerhans cell histiocytosis or germinoma at presentation and/or during
      follow-up of more than 1.5 years were reviewed. RESULTS: Age at presentation
      ranged from 3 to 14 years. Two patients had a positive family history of
      autoimmunity. Three children presented with associated growth failure, two with
      nausea and one with long-standing headache. Median maximal diameter of the stalk
      was 4.6 mm (2.7-10 mm). Four patients had extra-pituitary brain anomalies, such
      as cysts. One patient had central hypothyroidism, and another had a partial
      growth hormone deficiency at diagnosis. Within a mean follow-up of 5.4 (1.5-15)
      years, stalk thickening remained unchanged in two patients, regressed in one and
      normalized in six children. CDI remained in all, while additional pituitary
      hormone deficiencies developed in only one patient. CONCLUSIONS: In this series
      of children INH with CDI as initial presentation, CDI was permanent and
      infrequently associated with anterior pituitary hormone deficiencies, despite a
      frequent association with nonstalk cerebral lesions.

PMID- 28444955
TI  - Serum uric acid levels are associated with increased risk of newly developed
      diabetic retinopathy among Japanese male patients with type 2 diabetes: A
      prospective cohort study (diabetes distress and care registry at Tenri [DDCRT
      13]).
AB  - OBJECTIVE: We assessed the prospective association between baseline serum uric
      acid levels and consequent risk of developing diabetic retinopathy. RESEARCH
      DESIGN AND METHODS: Data for 1839 type 2 diabetes patients without diabetic
      retinopathy were obtained from a Japanese diabetes registry. A Cox proportional
      hazards model with time-varying exposure information by sex was used and adjusted
      for potential confounders to assess the independent correlations between baseline
      serum uric acid levels and incidence rate of diabetic retinopathy. RESULTS: Newly
      developed diabetic retinopathy was recognized in 188 patients (10.2%) during the
      observation period of 2 years. Compared to the first serum uric acid quartile
      level, the multivariate adjusted hazards ratio for diabetic retinopathy
      development in male patients was 1.97 (95% CI, 1.14-3.41; P = .015), 1.92 (95%
      CI, 1.18-3.13; P = .008), and 2.17 (95% CI, 1.40-3.37; P = .001) for the second,
      third, and fourth serum uric acid quartile levels, respectively. But this was not
      the case with female patients. CONCLUSION: Higher serum uric acid levels were
      associated with increased risk of developing diabetic retinopathy in male
      patients with type 2 diabetes, but not in female patients. Serum uric acid may be
      a useful biomarker for predicting the future risk of developing diabetic
      retinopathy in male patients with type 2 diabetes.

PMID- 28444956
TI  - Structural Insights into the Recognition of N2 -Aryl- and C8-Aryl DNA Lesions by
      the Repair Protein XPA/Rad14.
AB  - Aromatic amines are strongly carcinogenic. They are activated in the liver to
      give reactive nitrenium ions that react with nucleobases within the DNA duplex.
      The reaction occurs predominantly at the C8 position of the dG base, thereby
      giving C8-acetyl-aryl- or C8-aryl-dG adducts in an electrophilic aromatic
      substitution reaction. Alternatively, reaction with the exocyclic 2-NH2 group is
      observed. Although the C8 adducts retain base-pairing properties, base pairing is
      strongly compromised in the case of the N2 adducts. Here we show crystal
      structures of two DNA lesions, N2 -acetylnaphthyl-dG and C8-fluorenyl-dG, within
      a DNA duplex recognized by the repair protein Rad14. The structures confirm that
      two molecules of the repair protein recognize the lesion and induce a 72 or 78
      degrees  kink at the site of the damage. Importantly, the same overall kinked
      structure is induced by binding of the repair proteins, although the structurally
      different lesions result in distinct stacking interactions of the lesions within
      the duplex. The results suggest that the repair protein XPA/Rad14 is a sensor
      that recognizes flexibility. The protein converts the information that
      structurally different lesions are present in the duplex into a unifying sharply
      kinked recognition motif.

PMID- 28444957
TI  - Epidemiology of endometriosis: a large population-based database study from a
      healthcare provider with 2 million members.
AB  - OBJECTIVE: Endometriosis constitutes a significant burden on the quality of life
      of women, their families and healthcare systems. The objective of this study is
      to describe the real-world epidemiology of endometriosis in an unselected low
      risk population in Israel. DESIGN: Retrospective population-based study. SETTING
      AND SAMPLE: The computerised databases of Maccabi Healthcare Services (MHS), a 2
      million-member healthcare provider representing a quarter of the Israeli
      population. METHODS: The crude point prevalence (31 December 2015; diagnosed
      since 1998) and annual incidence (2000-2015) rates of diagnosed endometriosis
      (ICD-9-CM 617.xx) were assessed among women aged 15-55 years. Prevalent patients
      were characterised in terms of sociodemographic and clinical characteristics,
      including validated MHS infertility and chronic disease registries. MAIN OUTCOME
      MEASURES: Prevalence and incidence of diagnosed endometriosis in MHS. RESULTS:
      The point prevalence of endometriosis [n = 6146, mean age 40.4 +/- 8.0 years
      (SD)] was 10.8 per 1000 (95% CI 10.5-11.0). Women aged 40-44 years had the
      highest prevalence rate of 18.6 per 1000 (95% CI 17.7-19.5). Infertility was
      documented in 37% of patients. A total of 6045 patients were included in the
      cohort of newly-diagnosed endometriosis (mean age 34.0 +/- 8.1 years),
      corresponding to an average annual incidence rate of 7.2 per 10 000 (95% CI 6.5
      8.0). CONCLUSIONS: We observed a substantially lower prevalence of diagnosed
      endometriosis compared with previous reports in high-risk populations, in line
      with population-based estimates from European databases (range 0.8-1.8%). Further
      characterisation of this cohort may help to understand what affects the
      prevalence of endometriosis in Israel, and to promote earlier diagnosis and
      improve management in clinical practice. TWEETABLE ABSTRACT: Endometriosis
      diagnosed in 1% of women, according to a large population-based study in a
      community setting.

PMID- 28444958
TI  - Role of Cytochrome P450 3A4 and 1A2 Phenotyping in Patients with Advanced Non
      small-Cell Lung Cancer Receiving Erlotinib Treatment.
AB  - Erlotinib is metabolized by cytochrome p450 (CYP) 3A and CYP1A. This study
      assessed CYP3A4 (midazolam) and CYP1A2 (caffeine) phenotyping in plasma and dried
      blood spots (DBS) for predicting the pharmacokinetics and toxicity of erlotinib
      in 36 patients with advanced NSCLC. On day 1, erlotinib 150 mg OD was initiated,
      and the two oral probe drugs midazolam (2 mg) and caffeine (100 mg) were added on
      day 1. Plasma and DBS were collected for erlotinib, OSI-420 and probe drugs for
      up to 6 hr on day 1 and 2-weekly up to week 10. Probe drugs, erlotinib and OSI
      420 were analysed using LC-MS-MS, and PK data were processed using population
      modelling. A high correlation was found between plasma and DBS concentrations for
      erlotinib (R2  = 0.960, p < 0.0001), OSI-420 (R2  = 0.971, p < 0.0001), midazolam
      (R2  = 0.995, p < 0.0001) and caffeine (R2  = 0.968, p < 0.0001). Apparent oral
      caffeine clearance was significantly correlated with erlotinib clearance (R2  =
      0.33, p = 0.048), while midazolam clearance was not (R2  = -0.09, p = 0.596).
      Erlotinib clearance was lower in patients experiencing grade 2 or 3 rash as
      compared to patients experiencing grade 0 or 1 rash (3.15 versus 3.93 L/hr, p =
      0.086 for Student's t-test). The results suggest that probe drug phenotyping is
      unlikely to substitute therapeutic drug monitoring of erlotinib in patients with
      advanced NSCLC, but erlotinib PK sampling from DBS may replace more invasive
      venous sampling and facilitate TDM in patients with cancer.

PMID- 28444959
TI  - Controlling and Monitoring Intracellular Delivery of Anticancer Polymer
      Nanomedicines.
AB  - Polymer nanomedicines are very attractive to improve the delivery of
      chemotherapeutics. Polymer conjugates and other polymer-based nanocarriers allow
      to increase plasma half-life and drug bioavailability and can also be guided
      toward tumors using passive and active targeting strategies. Since many
      chemotherapeutics act on targets that are located in well-defined subcellular
      compartments, other important factors that contribute to an efficient therapy
      include cellular internalization and subsequent intracellular trafficking of the
      polymer nanomedicines and/or its payload to the appropriate organelle in the
      cytoplasm. This article provides an overview of the different approaches that
      have been developed to control intracellular delivery of polymer nanomedicines
      and discusses the different techniques that can be used to monitor these
      processes.

PMID- 28444960
TI  - In vivo absorption and metabolism of leptosperin and methyl syringate, abundantly
      present in manuka honey.
AB  - SCOPE: Manuka honey, which shows strong nonperoxide-dependent antibacterial
      activity, contains unique components, such as methyl syringate 4-O-beta-D
      gentiobioside (leptosperin) and its aglycone, methyl syringate (MSYR). To
      determine the potential for biological activity evoked by the ingestion of
      leptosperin and MSYR, we investigated the absorption and metabolism of these
      components in manuka honey. METHODS AND RESULTS: The incubation of MSYR with
      liver microsomes or S9 fractions in vitro resulted in the formation of MSYR
      glucuronide (MSYR-GA), MSYR-sulfate (MSYR-S), and syringic acid as metabolites.
      Then, manuka honey (15 g) was fed to healthy human volunteers. MSYR-GA, MSYR-S,
      and MSYR were detected in both plasma and urine. Within plasma, their levels were
      highest within 0.5 h to 1 h post-ingestion, and most metabolites disappeared
      within 3 h. In conjunction with the disappearances, a significant amount of
      metabolites along with trace leptosperin was excreted in urine within 4 h. To
      elucidate the detailed metabolisms of leptosperin and MSYR, each compound was
      separately administered to mice. In each case, MSYR-GA, MSYR-S, and MSYR were
      detected in both plasma and urine. CONCLUSION: This study shows the major
      molecular pathway for leptosperin and MSYR metabolism and could facilitate an
      understanding of biological functions of manuka honey post ingestion.

PMID- 28444961
TI  - Biodiversity and ecosystem function: making sense of numerous species
      interactions in multi-species communities.
AB  - Understanding the biodiversity and ecosystem function relationship can be
      challenging in species-rich ecosystems. Traditionally, species richness has been
      relied on heavily to explain changes in ecosystem function across diversity
      gradients. Diversity-Interactions models can test how ecosystem function is
      affected by species identity, species interactions, and evenness, in addition to
      richness. However, in a species-rich system, there may be too many species
      interactions to allow estimation of each coefficient, and if all interaction
      coefficients are estimable, they may be devoid of any sensible biological
      meaning. Parsimonious descriptions using constraints among interaction
      coefficients have been developed but important variability may still remain
      unexplained. Here, we extend Diversity-Interactions models to describe the
      effects of diversity on ecosystem function using a combination of fixed
      coefficients and random effects. Our approach provides improved standard errors
      for testing fixed coefficients and incorporates lack-of-fit tests for diversity
      effects. We illustrate our methods using data from a grassland and a microbial
      experiment. Our framework considerably reduces the complexities associated with
      understanding how species interactions contribute to ecosystem function in
      species-rich ecosystems.

PMID- 28444962
TI  - Fine-scale species distribution changes in a mixed oak stand over two successive
      generations.
AB  - Large-scale tree distribution changes have received considerable attention but
      underlying demo-genetic mechanisms are less well documented. We used a diachronic
      approach to track species shifts in a mixed oak stand (Quercus petraea-Quercus
      robur) at a fine spatiotemporal scale. Species assignment was made using single
      nucleotide polymorphism (SNP) fingerprints employing clustering and parentage
      analysis. Mating patterns and reproductive success were assessed by parentage
      analysis. Plot-based inventories of soil parameters and sapling densities
      provided ecological and demographic information, respectively. Sapling density
      and reproductive success was higher in Q. petraea than in Q. robur, and were
      correlated with a spatial expansion of Q. petraea (50% to 67% of the area).
      Admixed trees resulting from hybridization and backcrossing between the two
      species were more frequent under the Q. robur canopy. We suspect that species'
      differential responses to ongoing environmental changes and interspecific
      competition are the predominant factors accounting for the recruitment success of
      Q. petraea, while human interference, differential reproduction and hybridization
      (and backcrossings) are probably of more limited importance. We anticipate in
      mixed Q. petraea-Q. robur stands, under current ongoing environmental change,
      that these processes will be enhanced, at least in the western part of the
      distribution of the two species.

PMID- 28444963
TI  - The influence of frontal alpha-asymmetry on the processing of approach- and
      withdrawal-related stimuli-A multichannel psychophysiology study.
AB  - The approach-withdrawal model of hemispheric activation suggests that left
      frontal cortical areas mediate approach, while right frontal cortical areas
      mediate withdrawal motivation. Within this framework, the present study
      investigates the association of frontal cortical asymmetry with attentional and
      emotional responses toward approach- and withdrawal-related emotional stimuli.
      Resting frontal asymmetry was measured from 43 students before they passively
      viewed negative, neutral, and positive emotional pictures. The startle reflex,
      skin conductance response, and subjective ratings of valence and arousal were
      assessed to quantify emotional responding, while attention was assessed with
      ERPs. We also assessed frontal asymmetry in response to the pictures. Results
      indicated that relatively stronger right frontal cortical activation was
      associated with increased N1 amplitudes and more negative subjective emotional
      evaluation of all stimuli. Furthermore, enhanced right frontal asymmetry (state
      and trait) was associated with diminished emotional modulation of the late
      positive potential. In contrast, no association of frontal asymmetry with
      defensive reflex physiology or activation of sympathetic nervous system activity
      was found. The current data suggest dissociable influence of resting frontal
      brain asymmetry on attentional and physiological processing of withdrawal- and
      approach-related stimuli. That is, asymmetrical frontal cortical brain activation
      might not modulate approach-/withdrawal-related motor responses and sympathetic
      arousal directly, but instead enhances allocation of attentional resources to
      subjectively significant stimuli. The results are discussed in terms of their
      potential importance for emotion perception in anxiety disorders and their
      contribution to the understanding of frontal asymmetry.

PMID- 28444964
TI  - Randomized clinical trial of landiolol hydrochloride for the prevention of atrial
      fibrillation and postoperative complications after oesophagectomy for cancer.
AB  - BACKGROUND: Atrial fibrillation is common after oesophageal surgery. The aim of
      this study was to evaluate whether landiolol hydrochloride was effective and safe
      in the prevention of atrial fibrillation after oesophagectomy, and to see whether
      a reduction in incidence of atrial fibrillation would reduce other postoperative
      complications. METHODS: This single-centre study enrolled patients scheduled for
      transthoracic oesophagectomy in a randomized, double-blind, placebo-controlled
      trial between March 2013 and January 2016. Enrolled patients were randomized with
      a 1 : 1 parallel allocation ratio to either landiolol prophylaxis or placebo. The
      primary endpoint was the occurrence of atrial fibrillation after oesophagectomy.
      Secondary endpoints were incidence of postoperative complications, and effects on
      haemodynamic and inflammatory indices. RESULTS: One hundred patients were
      enrolled, 50 in each group. Postoperative atrial fibrillation occurred in 15
      patients (30 per cent) receiving placebo versus five (10 per cent) receiving
      landiolol (P = 0.012). The overall incidence of postoperative complications was
      significantly lower in the landiolol group (P = 0.046). In the landiolol group,
      postoperative heart rate was suppressed effectively, but the decrease in BP was
      not harmful. The interleukin 6 level was significantly lower on days 3 and 5
      after surgery in the landiolol group (P = 0.001 and P = 0.002 respectively).
      CONCLUSION: Landiolol was effective and safe in preventing atrial fibrillation
      after oesophagectomy. Registration number: UMIN000010648
      (http://www.umin.ac.jp/ctr/).

PMID- 28444965
TI  - Serum free light chain quantitative assays: Dilemma of a biomarker.
AB  - BACKGROUND: Serum free light chains detection assays are consistently meeting
      greater interest for the diagnosis and monitoring of monoclonal gammopathies and
      plasma cell dyscrasias. Nowadays, there are neither standardized methods nor
      reference material for the determination of free light chains; for this reason,
      it is important to compare two different assays used in clinical laboratory.
      METHODS: We evaluated 300 serum samples from patients with B-cell disorders and
      compared the analytical performances of both assay. Each test was assayed on both
      testing platforms (Siemens Dade Behring BN II Nephelometer and SPAPLUS by The
      Binding Site). kappa/lambda ratios were determined and compared. Results were
      analyzed by Passing-Bablok and Bland-Altman plots to evaluate comparability of
      the two techniques and to determine bias. RESULTS: The reproducibility of both
      assays is acceptable, reaching minimum and desirable analytical goals derived
      from biological variability. However, values are not interchangeable between
      systems. This study shows that the two systems do not allow results to be
      transferred from one method to the other even if they display good agreement.
      CONCLUSION: Our study highlights the importance of elaborating an international
      standard for free light chains quantification in order to offer homogeneous
      results as well as guarantee harmonization of values among laboratories.
      Moreover, the assays should be validated in specific patient groups to determine
      that they are clinically fit for purpose.

PMID- 28444966
TI  - Correlation between genetic polymorphisms within the MAPK1/HIF-1/HO-1 signaling
      pathway and risk or prognosis of perimenopausal coronary artery disease.
AB  - BACKGROUND: Mitogen-activated protein kinase-1 (MAPK1), as well as its downstream
      factors of hypoxia-inducible factor-1 (HIF-1) and heme oxygenase-1 (HO-1), have
      been documented to be involved in modulating development of coronary artery
      disease (CAD). HYPOTHESIS: Genetic mutations within the MAPK1/HIF-1/HO-1
      signaling pathway could alter the risk of perimenopausal CAD in Chinese patients.
      METHODS: Peripheral blood samples were gathered from 589 CAD patients and 860
      healthy controls, and 12 potential single-nucleotide polymorphisms (SNPs) were
      obtained from HapMap database and previously published studies. Genotyping of
      SNPs was implemented with the TaqMan SNP Genotyping Assays. Odds ratios (OR) and
      95% confidence intervals (CI) were utilized to evaluate the correlations between
      SNPs and CAD risk. RESULTS: Regarding MAPK1 , rs6928 (OR: 1.71, 95% CI: 1.47
      1.98, P < 0.05), rs9340 (OR: 0.85, 95% CI: 0.73-0.99, P < 0.05), and rs11913721
      (OR: 0.70, 95% CI: 0.52-0.95, P < 0.05) were remarkably associated with
      susceptibility to perimenopausal CAD. Of these, rs9340 and rs11913721 were also
      regarded as protective factors for perimenopausal CAD patients. Moreover, results
      of HIF-1 indicated noticeable correlations between combined SNPs of rs1087314 and
      rs2057482 and risk of perimenopausal CAD (OR: 1.24, 95% CI: 1.01-1.53, P < 0.05;
      and OR: 0.71, 95% CI: 0.55-0.91, P < 0.05, respectively). Nonetheless, rs2071746
      in HO-1 was found to be only associated with perimenopausal CAD risk (OR: 0.67,
      95% CI: 0.58-0.78, P < 0.05). CONCLUSIONS: The genetic mutations within MAPK1
      (rs6928, rs9340, rs11913721), HIF-1 (rs1087314, rs2057482), and HO-1 (rs2071746)
      could alter susceptibility to perimenopausal CAD in this Chinese population.

PMID- 28444968
TI  - Carcinoembryonic antigen directed PET-CECT scanning for postoperative
      surveillance of colorectal cancer.
AB  - AIM: During the follow-up of surgically resected colorectal cancer (CRC),
      positron emission tomography-contrast-enhanced computed tomography (PET-CECT) is
      indicated for asymptomatic elevation of carcinoembryonic antigen (CEA) > 5 ng/ml
      and no obvious site of recurrence on clinical examination and basic imaging. As
      an institutional policy, a PET-CECT scan was performed at our institute whenever
      (1) CEA levels rose above 5 ng/ml and (2) CEA values were doubled (even if the
      CEA level was < 5 ng/ml). Our aim was to correlate the range of CEA elevation
      with recurrence rates and to evaluate the diagnostic utility of PET-CECT scanning
      in this setting. METHOD: We retrospectively analysed all cases where a PET-CECT
      scan was performed for elevated CEA levels during surveillance visits after
      complete resection of the primary tumour followed by adjuvant therapy. This study
      was conducted from 1 January 2013 to 31 July 2015. RESULTS: In all, 104 patients
      underwent a PET-CECT scan for rising CEA values, and 62 patients (59.6%) were
      found to have recurrent disease. At CEA levels < 5, 5.1-10, 10.1-15, 15.1-50 and
      > 50 ng/ml, disease recurred in 10%, 45%, 70%, 94% and 100% patients,
      respectively. Sensitivity, specificity, positive predictive value and negative
      predictive value of the PET-CECT scan were 92.7%, 95.2%, 96.2% and 90.9%,
      respectively. Elevation of CEA levels during follow-up was indicative of
      recurrence in 68% of the secretors and 45% of the non-secretors (based on
      baseline CEA status). CONCLUSION: In the setting of rising CEA levels during
      follow-up of patients with CRC, a PET-CECT scan is a valuable tool to detect
      recurrence, irrespective of the baseline CEA secretor status. The likelihood of
      recurrence of disease was directly proportional to the value of the raised CEA
      level.

PMID- 28444967
TI  - Co-delivery of microRNA-21 antisense oligonucleotides and gemcitabine using
      nanomedicine for pancreatic cancer therapy.
AB  - Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of
      chemotherapy is usually poor. Precision medicine, combining downregulation of
      target genes with chemotherapy drugs, is expected to improve therapeutic effects.
      Therefore, we developed a combined therapy of microRNA-21 antisense
      oligonucleotides (ASO-miR-21) and gemcitabine (Gem) using a targeted co-delivery
      nanoparticle (NP) carrier and investigated the synergistic inhibitory effects on
      pancreatic cancer cells metastasis and growth. Polyethylene glycol
      polyethylenimine-magnetic iron oxide NPs were used to co-deliver ASO-miR-21 and
      Gem. An anti-CD44v6 single-chain variable fragment (scFvCD44v6 ) was used to coat
      the particles to obtain active and targeted delivery. Our results showed that the
      downregulation of the oncogenic miR-21 by ASO resulted in upregulation of the
      tumor-suppressor genes PDCD4 and PTEN and the suppression of epithelial
      mesenchymal transition, which inhibited the proliferation and induced the clonal
      formation, migration, and invasion of pancreatic cancer cells in vitro. The co
      delivery of ASO-miR-21 and Gem induced more cell apoptosis and inhibited the
      growth of pancreatic cancer cells to a greater extent than single ASO-miR-21 or
      Gem treatment in vitro. In animal tests, more scFvCD44v6 -PEG
      polyethylenimine/ASO-magnetic iron oxide NP/Gem accumulated at the tumor site
      than non-targeted NPs and induced a potent inhibition of tumor proliferation and
      metastasis. Magnetic resonance imaging was used to observed tumor homing of NPs.
      These results imply that the combination of miR-21 gene silencing and Gem therapy
      using an scFv-functionalized NP carrier exerted synergistic antitumor effects on
      pancreatic cancer cells, which is a promising strategy for pancreatic cancer
      therapy.

PMID- 28444970
TI  - Quality of life of immigrant and non-immigrant infertile patients in a publicly
      funded in vitro fertilisation program: a cross-sectional study.
AB  - OBJECTIVE: To investigate whether there are differences in fertility quality of
      life (FertiQoL) and socio-demographic characteristics between immigrants and non
      immigrant patients attending a government-funded fertility program. DESIGN: Cross
      sectional study. SETTING: McGill University Reproductive Center in Montreal,
      Canada, at a time when governmental funding for in vitro fertilisation (IVF) was
      provided to all residents. POPULATION: All infertile patients, males and females,
      attending the center between March and July 2015. METHODS: Patients were invited
      to complete anonymous questionnaires which included socio-demographic items and
      the validated FertiQoL questionnaire. MAIN OUTCOME MEASURES: Socio-demographic
      characteristics (age, gender, marital state, infertility type & duration,
      previous IVF attempts; education, employment, income, ethnicity, spoken
      languages) and FertiQoL scores. RESULTS: In all, 1020 patients completed the
      questionnaires; of these, 752 (77.7%) non-immigrant Canadian citizens and 215
      (22.3%) resident immigrants were included in the analysis. Median duration in
      Canada for immigrants was 4 years. Immigrants were more likely to have
      university/graduate degrees (75% versus 64%), to be unemployed (37% versus 13.1%)
      and to have lower annual household incomes (72.8% versus 39.5%, all P < 0.05).
      They also reported poorer QoL and achieved significantly lower scores in the
      emotional, mind/body, social, treatment and total FertiQoL domains. Multivariate
      analysis showed male gender, lower education level and Caucasian/European
      ethnicity to be significantly associated with higher QoL. CONCLUSIONS: Despite
      governmental funding of IVF, immigrants experience reduced fertility QoL,
      implying cost is not the only barrier to IVF use. The reduced QoL may stem from
      cross-cultural differences in infertility perception. This population may be at
      greater risk for depression and anxiety and should be flagged accordingly.
      TWEETABLE ABSTRACT: Immigrants' fertility QoL is lower despite publicly funded
      IVF implying cost is not the only barrier to IVF use.

PMID- 28444971
TI  - 2017 Annual Meeting of the Orthopaedic Research Society, San Diego, CA, March 19
      22, 2017.
AB  - Searchable abstracts may be found at http://www.ors.org/abstract-search/.

PMID- 28444969
TI  - Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer.
AB  - Several lines of evidence indicate that during transformation epithelial cancer
      cells can acquire mesenchymal features via a process called epithelial-to
      mesenchymal transition (EMT). This process endows cancer cells with increased
      invasive and migratory capacity, enabling tumour dissemination and metastasis.
      EMT is associated with a complex metabolic reprogramming, orchestrated by EMT
      transcription factors, which support the energy requirements of increased
      motility and growth in harsh environmental conditions. The discovery that
      mutations in metabolic genes such as FH, SDH and IDH activate EMT provided
      further evidence that EMT and metabolism are intertwined. In this review, we
      discuss the role of EMT in cancer and the underpinning metabolic reprogramming.
      We also put forward the hypothesis that, by altering chromatin structure and
      function, metabolic pathways engaged by EMT are necessary for its full
      activation.

PMID- 28444972
TI  - Production and application of a thermostable lipase from Serratia marcescens in
      detergent formulation and biodiesel production.
AB  - In this study, extracellular lipase was produced by Serratia marcescens wild type
      and three mutant strains. The maximum lipase activity (80 U/mL) was obtained with
      the SMRG4 mutant strain using soybean oil. Using a 22 factorial design, the
      lipase production increased 1.55-fold (124 U/mL) with 4% and 0.05% of soybean oil
      and Triton X-100, respectively. The optimum conditions for maximum lipase
      activity were 50  degrees C and pH 8. However, the enzyme was active in a broad
      range of pH (6-10) and temperatures (5-55  degrees C). This lipase was stable in
      organic solvents and in the presence of oxidizing agents. The enzyme also proved
      to be efficient for the removal of triacylglycerol from olive oil in cotton
      cloth. A Box-Behnken experimental design was used to evaluate the effects of the
      interactions between total lipase activity, buffer pH, and wash temperatures on
      oil removal. The model obtained suggested that all selected factors had a
      significant impact on oil removal, with optimum conditions of 550 U lipase, 45 
      degrees C, pH 9.5, with 79.45% removal. Biotransformation of waste frying oil
      using the enzyme and in presence of methanol resulted in the synthesis of methyl
      esters such as methyl oleate, methyl palmitate, and methyl stearate.

PMID- 28444973
TI  - In depth comparative phenotyping of blood innate myeloid leukocytes from healthy
      humans and macaques using mass cytometry.
AB  - Comparative immune-profiling of innate responses in humans and non-human primates
      is important to understand the pathogenesis of infectious and chronic
      inflammatory diseases as well as for the preclinical development of vaccines and
      immune therapies. However, direct comparisons of the two species are rare and
      were never performed using mass cytometry. Here, whole-blood-derived leukocytes
      from healthy humans and cynomolgus macaques were analyzed with mass cytometry.
      Two similar panels of around 30 monoclonal antibodies targeting human markers
      associated with innate myeloid cells to stain fixed human and macaque leukocytes
      were constructed. To compare the circulating innate cells from the two primate
      species, an analysis pipeline combining a clustering analysis by the Spanning
      tree Progression Analysis of Density-normalized Events (SPADE) algorithm with a
      two-step hierarchical clustering of cells nodes and markers was used. Identical
      SPADE settings were applied to both datasets, except for the 20 clustering
      markers which slightly differed. A correlation analysis designed to compare the
      phenotypes of human and macaque cell nodes and based on 16 markers, including 15
      shared clustering markers and CD19 for humans or CD20 for macaques, revealed
      similarities and differences between staining patterns. This study unique by the
      number of individuals (26 humans and 5 macaques) and the use of mass cytometry
      certainly contributes to better assess the advantages and limits of the use of
      non-human primates in preclinical research. (c) 2017 International Society for
      Advancement of Cytometry.

PMID- 28444975
TI  - Dissociation between the neural correlates of conscious face perception and
      visual attention.
AB  - Given the higher chance to recognize attended compared to unattended stimuli, the
      specific neural correlates of these two processes, attention and awareness, tend
      to be intermingled in experimental designs. In this study, we dissociated the
      neural correlates of conscious face perception from the effects of visual
      attention. To do this, we presented faces at the threshold of awareness and
      manipulated attention through the use of exogenous prestimulus cues. We show that
      the N170 component, a scalp EEG marker of face perception, was modulated
      independently by attention and by awareness. An earlier P1 component was not
      modulated by either of the two effects and a later P3 component was indicative of
      awareness but not of attention. These claims are supported by converging evidence
      from (a) modulations observed in the average evoked potentials, (b) correlations
      between neural and behavioral data at the single-subject level, and (c) single
      trial analyses. Overall, our results show a clear dissociation between the neural
      substrates of attention and awareness. Based on these results, we argue that
      conscious face perception is triggered by a boost in face-selective cortical
      ensembles that can be modulated by, but are still independent from, visual
      attention.

PMID- 28444974
TI  - School-based surveillance for influenza vaccine effectiveness during 2014-2015
      seasons in Hong Kong.
AB  - BACKGROUND: Influenza imposes substantial healthcare burden in children, which
      can be prevented by vaccination. Influenza vaccination coverage varies widely
      among childhood populations worldwide, which has significant impact on herd
      immunity and usefulness of influenza vaccine. However, there are limited real
      life data on influenza vaccine effectiveness (VE) in children. OBJECTIVE: This
      prospective study aimed to investigate clinical spectrum of childhood influenza
      and VE in preventing influenza in Hong Kong children. METHODS: A total of 623
      children were recruited from 15 kindergartens and primary schools. Parents
      completed a questionnaire on subjects' health and influenza vaccination history.
      Flocked nasopharyngeal swabs (FNPSs) were collected in biweekly school visits
      during 2014-2015 influenza seasons. Influenza A and B viruses were detected and
      typed by molecular assays. RESULTS: A total of 2633 FNPS samples were collected,
      with two or more samples being obtained from 607 (97.4%) of subjects. Thirty-six
      (11.2%) subjects had influenza A or B in 2014, whereas all 19 (6.3%) subjects
      identified in 2015 had influenza A. Ninety-nine subjects reported influenza-like
      illness (ILI), and nine illness visits were arranged. Influenza vaccination was
      protective against ILI but not mild laboratory-confirmed influenza by
      surveillance. Moderate overall influenza VE of 42%-52% was observed for ILI, and
      subgroup analyses showed much higher VE for both ILI (70.9% vs 34.6%) and mild
      laboratory-confirmed influenza (44.0% vs -6.2%) in school-age children than
      preschoolers who were vaccinated within 12 months. CONCLUSIONS: Mild laboratory
      confirmed influenza infection is common in children during influenza seasons.
      Influenza vaccination is effective against ILI but not mild infection identified
      by surveillance.

PMID- 28444976
TI  - Association of lipoprotein(a) with long-term mortality following coronary
      angiography or percutaneous coronary intervention.
AB  - BACKGROUND: There is no consistent evidence to suggest the association of plasma
      lipoprotein(a) (Lp[a]) with long-term mortality in patients undergoing coronary
      angiography (CAG) or percutaneous coronary intervention (PCI). HYPOTHESIS: Level
      of Lp(a) is associated with long-term mortality following CAG or PCI. METHODS: We
      enrolled 1684 patients with plasma Lp(a) data undergoing CAG or PCI between April
      2009 and December 2013. The patients were divided into 2 groups: a low-Lp(a)
      group (Lp[a] <16.0 mg/dL; n = 842) and a high-Lp(a) group (Lp[a] >=16.0 mg/dL; n
      = 842). RESULTS: In-hospital mortality was not significantly different between
      the high and low Lp(a) groups (0.8% vs 0.5%, respectively; P = 0.364). During the
      median follow-up period of 1.95 years, the high-Lp(a) group had a higher long
      term mortality than did the low-Lp(a) group (5.8% vs 2.5%, respectively; P =
      0.003). After adjustment of confounders, multivariate Cox regression analysis
      revealed that a higher Lp(a) level was an independent predictor of long-term
      mortality (hazard ratio: 1.96, 95% confidence interval: 1.07-3.59, P = 0.029).
      CONCLUSIONS: Our data suggested that an elevated Lp(a) level was significantly
      associated with long-term mortality following CAG or PCI. However, additional
      larger multicenter studies will be required to investigate the predictive value
      of Lp(a) levels and evaluate the benefit of controlling Lp(a) levels for patients
      undergoing CAG or PCI.

PMID- 28444978
TI  - Loss of CADM4 expression is associated with poor prognosis in small intestinal
      adenocarcinomas.
AB  - We evaluated the association of cell adhesion molecule 4 (CADM4) expression with
      clinicopathologic parameters and overall survival (OS) in patients with small
      intestinal adenocarcinomas (SIAs) and determined its prognostic significance.
      CADM4 immunohistochemical staining was performed for 170 SIA samples. Loss of or
      low CADM4 expression was observed in 26 (15.3%) and 50 (29.4%) cases,
      respectively, and it was significantly associated with undifferentiated histology
      (p < 0.044), high-grade tumor (p < 0.001), high pT3 or pT4 stage (p < 0.038),
      pancreatic invasion (p < 0.018), and lymphatic invasion (p < 0.020). Patients
      with CADM4 expression loss had significantly poorer OS (p < 0.042). On
      multivariate analysis, SIA in the jejunum and ileum, (hazard ratio [HR], 2.465;
      95% confidence interval [CI], 1.288-4.720; p = 0.006 and HR, 3.407; 95% CI, 1.515
      7.662; p = 0.003, respectively), signet ring cell carcinoma (HR, 92.388; 95% CI,
      14.813-576.230; p = 0.000), SIA with lymph node metastasis (HR, 3.223; 95% CI,
      1.697-6.124; p = 0.000), retroperitoneal seeding (HR, 3.696; 95% CI, 1.303
      10.479; p = 0.014), and CADM4 expression loss (HR, 2.348; 95% CI, 1.130-4.882; p
      = 0.022) were associated with poor OS. CADM4 expression loss is an important
      prognostic marker for SIA.

PMID- 28444977
TI  - Efficacy of postoperative prophylactic antibiotics in reducing permanent
      pacemaker infections.
AB  - BACKGROUND: Despite limited evidence, postoperative prophylactic antibiotics are
      often used in the setting of permanent pacemaker implantation or replacement. The
      aim of this study is to investigate the efficacy of postoperative antibiotics.
      HYPOTHESIS: Postoperative prophylactic antibiotics may be not clinically useful.
      METHODS: We recruited 367 consecutive patients undergoing permanent pacemaker
      implantation or generator replacement at a tertiary referral center. Baseline
      demographics, clinical characteristics, and procedure information were collected,
      and all patients received preoperative prophylactic antibiotics. Postoperative
      prophylactic antibiotics were administered at the discretion of the treating
      physician, and all patients were seen in follow-up every 3 to 6 months for an
      average follow-up period of 16 months. The primary endpoint was device-related
      infection. RESULTS: A total of 110 patients were treated with preoperative
      antibiotics only (group 1), whereas 257 patients received both preoperative and
      postoperative antibiotics (group 2). After a mean follow-up period of 16 months,
      1 patient in group 1 (0.9%) and 4 patients in group 2 (1.5%) experienced a device
      related infection. There was no significant difference in the rate of infection
      between the 2 groups (P = 0.624). In the univariate analysis, only the age (60 +/
      11 vs 75 +/- 12 years, P < 0.001) was significantly different between the
      infected and noninfected groups. In the multivariate analysis, younger age was an
      independent risk factor for infective complications (odds ratio = 1.08, P =
      0.016). CONCLUSIONS: Patients treated with preoperative and postoperative
      antibiotics had a similar rate of infection as those treated with preoperative
      antibiotics alone. Further studies are needed to confirm these preliminary
      findings.

PMID- 28444979
TI  - False negative single antigen bead assay: Is it always an effect of prozone?
AB  - BACKGROUND: Bead based flow cytometry and Luminex play a major role in
      identification of alloantibodies in renal transplant work-up. Strong
      sensitization events may lead to prozone phenomenon that can affect single
      antigen bead (SAB) assay and result in false negativity. However, this can also
      be due to high titer of other blocking antibodies. While methods like, heat
      inactivation, C1 inhibitor, Ethylene diamine tetra-acetic-acid and Dithio
      threitol treatment can remove interfering antibodies of complement and IgM, these
      methods are not optimal if false negativity is due to prozone effect, which is
      high titer of antibodies alone. METHODS: We hereby present a case of a highly
      sensitized renal transplant recipient with 64% panel reactive antibody positivity
      (PRA) and a subsequent negative SAB assay. This paradoxical finding hinted at SAB
      being a false negative result and serial dilutions were used to perform further
      tests. RESULTS: Serum dilutions lead to positive flow based panel reactive
      antibody (PRA) and flow cytometry crossmatch (FCXM), with an increasing trend in
      FCXM. CONCLUSIONS: In highly sensitized patients serial dilution should be
      considered during a transplant work-up to avoid missing any underlying
      antibodies. Serum dilution can be used as first option to circumvent prozone.
      Also, interference of other antibodies should not be labeled as prozone effect.

PMID- 28444980
TI  - Adolescent girls with asthma have worse asthma control and health-related quality
      of life than boys-A population based study.
AB  - BACKGROUND: Population-based studies investigating health-related quality of life
      (HRQoL) among asthmatic adolescents are rare. Further, among subjects with
      asthma, HRQoL may be affected by asthma control and severity. AIM: To investigate
      HRQoL in relation to asthma control and asthma severity among adolescents.
      METHOD: As a part of the population-based OLIN pediatric study, 266 adolescents
      with current asthma (14-15 yr) were identified. N = 247 completed the DISABKIDS
      HRQoL asthma module, including the domains impact and worry. The Asthma Control
      Test (ACT) was used and a disease severity score was calculated based on symptoms
      and medicine use. RESULTS: The prevalence of current asthma was 11%. Well
      controlled asthma was reported by 15% of the adolescents, and 53% had partly
      controlled asthma. The prevalence of uncontrolled asthma was significantly higher
      among girls than boys (38% vs 25%), and girls also reported lower HRQoL scores.
      There was a fairly strong correlation between the ACT and DISABKIDS scores.
      Independent risk factors for low HRQoL impact (a score <67) were female sex (OR
      4.66, 95%CI 1.82-9.54) and decreased ACT scores (1.38, 1.18-1.62). Risk factors
      for low HRQoL worry (a score <70) were female sex (3.33, 1.41-7.86), decreased
      ACT scores (1.35, 1.16-1.57), severe asthma (6.23, 1.46-16.50), and having
      current eczema (2.68, 1.00-7.24). CONCLUSION: Only a minority of the asthmatic
      adolescents reported well-controlled asthma, and poor asthma control and female
      sex were risk factors for low HRQoL. Our results demonstrate that evaluation of
      asthma control is of great importance for asthma management.

PMID- 28444981
TI  - Changing use and attitudes towards teledermatology in the U.K. over 10 years:
      results of the 2016 National Survey.

PMID- 28444982
TI  - Ionic-liquid-based ultrasound-assisted extraction of isoflavones from Belamcanda
      chinensis and subsequent screening and isolation of potential alpha-glucosidase
      inhibitors by ultrafiltration and semipreparative high-performance liquid
      chromatography.
AB  - The separation of a compound of interest from its structurally similar homologues
      to produce high-purity natural products is a challenging problem. This work
      proposes a novel method for the separation of iristectorigenin A from its
      structurally similar homologues by ionic-liquid-based ultrasound-assisted
      extraction and the subsequent screening and isolation of potential alpha
      glucosidase inhibitors via ultrafiltration and semipreparative high-performance
      liquid chromatography. Ionic-liquid-based ultrasound-assisted extraction was
      successfully applied to the extraction of tectorigenin, iristectorigenin A,
      irigenin, and irisflorentin from Belamcanda chinensis. The optimum conditions for
      the efficient extraction of isoflavones were determined as 1.0 M 1-ethyl-3
      methylimidazolium tetrafluoroborate with extraction time of 30 min and a solvent
      to solid ratio of 30 mL/g. Ultrafiltration with liquid chromatography and mass
      spectrometry was applied to screen and identify alpha-glucosidase inhibitors from
      B. chinensis, followed by the application of semipreparative high-performance
      liquid chromatography to separate and isolate the active constituents. Four major
      compounds including tectorigenin, iristectorigenin A, irigenin, and irisflorentin
      were screened and identified as alpha-glucosidase inhibitors, and then the four
      active compounds abovementioned were subsequently isolated by semipreparative
      high-performance liquid chromatography (99.89, 88.97, 99.79, and 99.97% purity,
      respectively). The results demonstrate that ionic liquid extraction can be
      successfully applied to the extraction of isoflavones from B. chinensis.

PMID- 28444983
TI  - Azilsartan Medoxomil, an Angiotensin II Receptor Antagonist for the Treatment of
      Hypertension.
AB  - Azilsartan (AZL) medoxomil was approved by the United States Food and Drug
      Administration in 2011 for the treatment of hypertension and has shown promising
      results both in blood pressure (BP) reduction and in tolerability, but has not
      yet been taken into practice to the same extent as other angiotensin II receptor
      blockers (ARBs) that have been on the market for a longer period. AZL antagonizes
      the AT1 receptor for angiotensin II (ANG II), whereas angiotensin-converting
      enzyme inhibitors block the conversion of angiotensin I to ANG II, but not
      alternative routes of formation of ANG II. The bioavailability of AZL is about
      60% and it has a tmax of 1.5-3 hr and a half-life of approximately 11 hr. With
      its IC50 of 7.4 nM after 5 hr of drug washout in radioligand assays, AZL has a
      tighter and longer-lasting binding to the AT1 receptor by several orders of
      magnitude than other ARBs, which might lead to a more effective reduction in BP.
      Clinical studies have revealed that AZL doses of 40 and 80 mg/day reduce BP
      significantly better than maximal clinical doses of valsartan or olmesartan,
      while being well tolerated and exhibiting a spectrum of adverse effects
      comparable to those of other ARBs. These properties of AZL might lower the risk
      of cardiovascular disease and thereby reduce mortality rates. However, the
      existing mortality studies have not found this correlation, which should be
      further investigated.

PMID- 28444984
TI  - Abdominal adhesions in gynaecologic surgery after caesarean section: a
      longitudinal population-based register study.
AB  - OBJECTIVE: The aim of the study was to evaluate the association between abdominal
      adhesions at the time of gynaecologic surgery and a history of caesarean
      delivery, and to investigate obstetric factors contributing to adhesion formation
      after caesarean section (CS). DESIGN: Longitudinal population-based register
      study. SETTING: Sweden. POPULATION: Women undergoing benign hysterectomy and/or
      adnexal surgery in Sweden, 2000-2014, with a previous delivery during 1973-2013
      (n = 15 479). METHODS: Information about abdominal adhesions during
      gynaecological surgery, prior medical history, pregnancies and deliveries were
      retrieved from Swedish National Health and Quality registers. MAIN OUTCOME
      MEASURES: Adhesions. RESULTS: In women with previous CS, adhesions were present
      in 37%, compared with 10% of women with no previous CS [odds ratio (OR): 5.18,
      95% confidence interval (CI): 4.70-5.71]. Adhesions increased with the number of
      caesarean sections: 32% after one CS; 42% after two CS and 59% after three or
      more CS (P < 0.001). Regardless of the number of CS, factors at CS such as age
      >=35 years (aOR: 1.28, 95% CI: 1.05-1.55), body mass index (BMI) >=30 [adjusted
      OR (aOR): 1.91, 95% CI: 1.49-2.45] and postpartum infection (aOR: 1.55, 95% CI:
      1.05-2.30) increased the risk of adhesions. CONCLUSIONS: Presence of adhesions in
      abdominal gynaecological surgery is associated with women's personal history of
      caesarean delivery. The number of caesarean sections was the important predictor
      of adhesions; advanced age, obesity and postpartum infection further increased
      the incidence. TWEETABLE ABSTRACT: Repeat caesarean, age, obesity and infection
      increased the risk of pelvic adhesions after caesarean section.

PMID- 28444985
TI  - Membrane traffic control by hypoxia.

PMID- 28444986
TI  - Supported Ionic Liquids: A Versatile and Useful Class of Materials.
AB  - Supported ionic liquids (SILs) represent a class of materials with peculiar
      properties and a huge potential regarding their possible applications in
      different fields of chemistry. Herein, we report our ongoing research about the
      use of SILs as support for organocatalysts, their role as catalysts themselves,
      and their application as support and stabilizers of palladium nanoparticles
      (PdNPs). The use of SILs based materials allowed achieving good results.
      Moreover, in some cases, after the functionalization of the catalytic species
      with an ion-tag moiety, a release and catch approach was employed in order to
      improve the catalytic activity and to facilitate the recovery of the hybrid
      system formed by the catalyst adsorbed onto SILs materials. All the reported
      examples demonstrate the versatility of such SILs materials, which can represent
      powerful tools able to exert a large number of functions.

PMID- 28444987
TI  - Platelet count, spleen length, and platelet count-to-spleen length ratio for the
      diagnosis of oesophageal varices in people with chronic liver disease or portal
      vein thrombosis.
AB  - BACKGROUND: Current guidelines recommend screening of people with oesophageal
      varices via oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic
      cirrhosis. This requires that people repeatedly undergo unpleasant invasive
      procedures with their attendant risks, although half of these people have no
      identifiable oesophageal varices 10 years after the initial diagnosis of
      cirrhosis. Platelet count, spleen length, and platelet count-to-spleen length
      ratio are non-invasive tests proposed as triage tests for the diagnosis of
      oesophageal varices. OBJECTIVES: Primary objectives To determine the diagnostic
      accuracy of platelet count, spleen length, and platelet count-to-spleen length
      ratio for the diagnosis of oesophageal varices of any size in paediatric or adult
      patients with chronic liver disease or portal vein thrombosis, irrespective of
      aetiology. To investigate the accuracy of these non-invasive tests as triage or
      replacement of oesophago-gastro-duodenoscopy. Secondary objectives To compare the
      diagnostic accuracy of these same tests for the diagnosis of high-risk
      oesophageal varices in paediatric or adult patients with chronic liver disease or
      portal vein thrombosis, irrespective of aetiology.We aimed to perform pair-wise
      comparisons between the three index tests, while considering predefined cut-off
      values.We investigated sources of heterogeneity. SEARCH METHODS: The Cochrane
      Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary
      Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE
      (OvidSP), Embase (OvidSP), and Science Citation Index - Expanded (Web of Science)
      (14 June 2016). We applied no language or document-type restrictions. SELECTION
      CRITERIA: Studies evaluating the diagnostic accuracy of platelet count, spleen
      length, and platelet count-to-spleen length ratio for the diagnosis of
      oesophageal varices via oesophago-gastro-duodenoscopy as the reference standard
      in children or adults of any age with chronic liver disease or portal vein
      thrombosis, who did not have variceal bleeding. DATA COLLECTION AND ANALYSIS:
      Standard Cochrane methods as outlined in the Cochrane Handbook for Diagnostic
      Test of Accuracy Reviews. MAIN RESULTS: We included 71 studies, 67 of which
      enrolled only adults and four only children. All included studies were cross
      sectional and were undertaken at a tertiary care centre. Eight studies reported
      study results in abstracts or letters. We considered all but one of the included
      studies to be at high risk of bias. We had major concerns about defining the cut
      off value for the three index tests; most included studies derived the best cut
      off values a posteriori, thus overestimating accuracy; 16 studies were designed
      to validate the 909 (n/mm3)/mm cut-off value for platelet count-to-spleen length
      ratio. Enrolment of participants was not consecutive in six studies and was
      unclear in 31 studies. Thirty-four studies assessed enrolment consecutively.
      Eleven studies excluded some included participants from the analyses, and in only
      one study, the time interval between index tests and the reference standard was
      longer than three months. Diagnosis of varices of any size. Platelet count showed
      sensitivity of 0.71 (95% confidence interval (CI) 0.63 to 0.77) and specificity
      of 0.80 (95% CI 0.69 to 0.88) (cut-off value of around 150,000/mm3 from 140,000
      to 150,000/mm3; 10 studies, 2054 participants). When examining potential sources
      of heterogeneity, we found that of all predefined factors, only aetiology had a
      role: studies including participants with chronic hepatitis C reported different
      results when compared with studies including participants with mixed aetiologies
      (P = 0.036). Spleen length showed sensitivity of 0.85 (95% CI 0.75 to 0.91) and
      specificity of 0.54 (95% CI 0.46 to 0.62) (cut-off values of around 110 mm, from
      110 to 112.5 mm; 13 studies, 1489 participants). Summary estimates for detection
      of varices of any size showed sensitivity of 0.93 (95% CI 0.83 to 0.97) and
      specificity of 0.84 (95% CI 0.75 to 0.91) in 17 studies, and 2637 participants
      had a cut-off value for platelet count-to-spleen length ratio of 909 (n/mm3)/mm.
      We found no effect of predefined sources of heterogeneity. An overall indirect
      comparison of the HSROCs of the three index tests showed that platelet count-to
      spleen length ratio was the most accurate index test when compared with platelet
      count (P < 0.001) and spleen length (P < 0.001). Diagnosis of varices at high
      risk of bleeding. Platelet count showed sensitivity of 0.80 (95% CI 0.73 to 0.85)
      and specificity of 0.68 (95% CI 0.57 to 0.77) (cut-off value of around
      150,000/mm3 from 140,000 to 160,000/mm3; seven studies, 1671 participants). For
      spleen length, we obtained only a summary ROC curve as we found no common cut-off
      between studies (six studies, 883 participants). Platelet count-to-spleen length
      ratio showed sensitivity of 0.85 (95% CI 0.72 to 0.93) and specificity of 0.66
      (95% CI 0.52 to 0.77) (cut-off value of around 909 (n/mm3)/mm; from 897 to 921
      (n/mm3)/mm; seven studies, 642 participants). An overall indirect comparison of
      the HSROCs of the three index tests showed that platelet count-to-spleen length
      ratio was the most accurate index test when compared with platelet count (P =
      0.003) and spleen length (P < 0.001). DIagnosis of varices of any size in
      children. We found four studies including 277 children with different liver
      diseases and or portal vein thrombosis. Platelet count showed sensitivity of 0.71
      (95% CI 0.60 to 0.80) and specificity of 0.83 (95% CI 0.70 to 0.91) (cut-off
      value of around 115,000/mm3; four studies, 277 participants). Platelet count-to
      spleen length z-score ratio showed sensitivity of 0.74 (95% CI 0.65 to 0.81) and
      specificity of 0.64 (95% CI 0.36 to 0.84) (cut-off value of 25; two studies, 197
      participants). AUTHORS' CONCLUSIONS: Platelet count-to-spleen length ratio could
      be used to stratify the risk of oesophageal varices. This test can be used as a
      triage test before endoscopy, thus ruling out adults without varices. In the case
      of a ratio > 909 (n/mm3)/mm, the presence of oesophageal varices of any size can
      be excluded and only 7% of adults with varices of any size would be missed,
      allowing investigators to spare the number of oesophago-gastro-duodenoscopy
      examinations. This test is not accurate enough for identification of oesophageal
      varices at high risk of bleeding that require primary prophylaxis. Future studies
      should assess the diagnostic accuracy of this test in specific subgroups of
      patients, as well as its ability to predict variceal bleeding. New non-invasive
      tests should be examined.

PMID- 28444988
TI  - Inhibitory action of oxytocin on spontaneous contraction of rat distal colon by
      nitrergic mechanism: involvement of cyclic GMP and apamin-sensitive K+ channels.
AB  - AIM: The mechanisms underlying the inhibitory effects of oxytocin (OT) on colon
      tone are not totally understood. We explore the mechanisms of OT on spontaneous
      contractility in rat distal colon and identify the mediators involved in this
      action. METHODS: In rat distal colon strips, mechanical activity was analysed and
      the production of nitric oxide (NO) in tissue loaded with the fluorochrome DAF-FM
      was visualized by confocal microscopy. OT receptor (OTR) expression was
      determined by Western blotting and immunofluorescence. RESULTS: In rat distal
      colon, OT produced a concentration-dependent reduction in the spontaneous
      contraction, which was abolished by the OTR antagonist atosiban, the neural
      blocker tetrodotoxin and the inhibitor of neuronal nitric oxide synthase (nNOS)
      NPLA. The inhibitory effects of OT were not affected by propranolol, atropine,
      the nicotinic cholinoceptor blocker hexamethonium, the vasoactive intestinal
      peptide receptor antagonist VIPHyb, the P2 purinoceptor antagonist PPADS, the
      adenosine A1 receptors antagonist DPCPX and the prostacyclin receptor antagonist
      Ro1138452. The soluble guanylyl cyclase (sGC) inhibitor ODQ and the small
      conductance Ca2+ -activated K+ (Ca K+ ) channels blocker apamin significantly
      reduced the relaxation induced by OT, nicotine, sodium nitroprusside and the sGC
      activator BAY 41-2272. The neural release of NO elicited by OT was prevented by
      NPLA, tetrodotoxin and atosiban. The presence of the OTR and its co-localization
      with nNOS was detected by immunohistochemistry and Western blotting experiments.
      CONCLUSION: These results demonstrate the NO release from enteric neurones
      induced by activation of OTR mediates distal colon relaxation. sGC and small
      conductance Ca K+ channels are involved in this relaxation.

PMID- 28444989
TI  - Water-Soluble Naked Gold Nanoclusters Are Not Luminescent.
AB  - Here, the synthesis of water-dispersible naked gold nanoclusters (AuNCnaked ) is
      reported by a simple reduction of HAuCl4 with NaOH at room temperature, and it is
      shown that they are non-luminescent. They are then easily passivated with
      different thiols and adenosine monophosphate, leading to luminescent NCs. This is
      an important finding because the photoluminescence of the passivated NCs can now
      be clearly attributed to the ligand-AuNC surface interaction. These results are
      also highly relevant from the point of view of the preparation of luminescent NCs
      from the same NC batch. This strategy can be valuable for the preparation of a
      broad range of nano(bio)composites.

PMID- 28444990
TI  - Paradoxical psoriasiform reactions to antitumour necrosis factor-alpha drugs in
      hidradenitis suppurativa.

PMID- 28444991
TI  - New Hydrazides and Hydrazide-Hydrazones of 2,3-Dihalogen Substituted Propionic
      Acids: Synthesis and in vitro Antimicrobial Activity Evaluation.
AB  - The main aim of this research was the synthesis, spectral identification and in
      vitro antimicrobial evaluation of new hydrazides and hydrazide-hydrazones of 2,3
      dihalogen substituted propionic acids. New hydrazides were obtained by the
      substitution reaction of appropriate ethyl esters of 2,3-dihalogen substituted
      propionic acids with hydrazine hydrate. Then obtained hydrazides were subjected
      to condensation reaction with various aldehydes which yielded with new hydrazide
      hydrazone derivatives. All obtained compounds were identified on the basis of
      spectral methods (1 H-NMR, 13 C-NMR) and in vitro screened against a panel of
      bacterial and fungal strains according to EUCAST and CLSI guidelines.

PMID- 28444992
TI  - Effects of Post-traumatic Stress Disorder on Pregnancy among US Military
      Veterans: Lessons for Research on Stress and Racial Disparities.

PMID- 28444993
TI  - Comparative tumor promotion assessment of e-cigarette and cigarettes using the in
      vitro Bhas 42 cell transformation assay.
AB  - In vitro cell transformation assays (CTA) are used to assess the carcinogenic
      potential of chemicals and complex mixtures and can detect nongenotoxic as well
      as genotoxic carcinogens. The Bhas 42 CTA has been developed with both initiation
      and promotion protocols to distinguish between these two carcinogen classes.
      Cigarette smoke is known to be carcinogenic and is positive in in vitro
      genotoxicity assays. Cigarette smoke also contains nongenotoxic carcinogens and
      is a tumour promoter and cocarcinogen in vivo. We have combined a suite of in
      vitro assays to compare the relative biological effects of new categories of
      tobacco and nicotine products with traditional cigarettes. The Bhas promotion
      assay has been included in this test battery to provide an in vitro surrogate for
      detecting tumor promoters. The activity of an electronic cigarette (e-cigarette;
      Vype ePen) was compared to that of a reference cigarette (3R4F) in the promotion
      assay, using total particulate matter (TPM)/aerosol collected matter (ACM) and
      aqueous extracts (AqE) of product aerosol emissions. 3R4F TPM was positive in
      this assay at concentrations >=6 ug/mL, while e-cigarette ACM did not have any
      promoter activity. AqE was found to be a lesssuitable test matrix in this assay
      due to high cytotoxicity. This is the first study to use the Bhas assay to
      compare tobacco and nicotine products and demonstrates the potential for its
      future application as part of a product assessment framework. These data add to
      growing evidence suggesting that e-cigarettes may provide a safer alternative to
      traditional cigarettes. Environ. Mol. Mutagen. 58:190-198, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28444994
TI  - Induction of micronuclei and cell cycle arrest by some tri- and
      tetrachlorobiphenyls in mammalian cells deficient in xenobiotic-metabolizing
      enzymes.
AB  - Polychlorinated biphenyls (PCBs) are persistent organic pollutants with continued
      public health concerns. The lower chlorinated biphenyls are supposed to be
      mutagenic following metabolic activation. However, in a preliminary study, we
      recently observed induction of micronuclei by several PCBs in a subclone of
      Chinese hamster V79 cell line, V79-Mz, which is deficient in xenobiotic
      metabolizing enzyme activities. In this study, metabolism-free genotoxicity of
      PCBs was investigated, using 10 tri- and tetrachlorobiphenyls, in V79, V79-Mz,
      and human hepatoma (HepG2) cell lines. Among the four tetrachlorobiphenyls,
      2,4,4',5- and 2,3'4,4'-tetrachlorobiphenyl-both having a noncoplanar
      configuration-induced micronuclei in V79-Mz cells, while their coplanar analogs
      3,4,4',5- and 3,3',4,4'-tetrachlorobiphenyl were inactive. Furthermore, 2,3,3'-
      (PCB 20) and 2,3,4'-trichlorobiphenyl (PCB 22) started to induce micronuclei in
      V79-Mz cells at 10 MUM and higher concentrations, demonstrating more potent
      effects than observed with 2,2',3-, 2,2',4-, 2,2',5, and 2,4,4'
      trichlorobiphenyl. As representative compounds, PCB 20 and 22 induced micronuclei
      in relatively high concentrations in HepG2 cells (p53-proficient), though they
      did not induce Hprt gene mutations in V79-Mz cells. PCB 20 and 22 increased
      mitotic index and induced cell cycle arrest at the G2/M phase, with effects more
      potent in V79-Mz than in V79 cells. This study suggests that 2,3,4'- and 2,3,3'
      substituted PCBs are micronuclei inducers and G2/M arresters among a number of
      trichlorobiphenyls in mammalian cell lines, though with potency lower than that
      observed recently in V79-derived cells expressing human CYP2E1. Similarly, some
      noncoplanar tetrachlorobiphenyls possess metabolism-independent chromosome
      damaging potentials. Environ. Mol. Mutagen. 58:199-208, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28444995
TI  - Peripheral artery disease and risk of adverse outcomes in heart failure with
      preserved ejection fraction.
AB  - BACKGROUND: Peripheral artery disease (PAD) in heart failure with preserved
      ejection fraction (HFpEF) is associated with an increased mortality risk, but the
      risk of individual outcomes associated with PAD in this patient group is less
      clear. HYPOTHESIS: PAD is associated with adverse outcomes in HFpEF, including
      hospitalization and specific cardiovascular outcomes. METHODS: We examined the
      association between PAD and adverse outcomes in 3385 patients with HFpEF (mean
      age, 69 +/- 9.6 years; 49% male; 89% white) from the Treatment of Preserved
      Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT).
      Baseline PAD was identified by self-reported history and medical-record review.
      The following outcomes were adjudicated by a clinical endpoint committee:
      hospitalization, hospitalization for heart failure (HF), myocardial infarction,
      stroke, death, and cardiovascular death. RESULTS: Over a median follow-up of 3.4
      years (interquartile range, 2.0-4.9 years), an increased risk for hospitalization
      (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.16-1.60), myocardial
      infarction (HR: 1.69, 95% CI: 1.07-2.67), death (HR: 1.56, 95% CI: 1.22-1.99),
      and cardiovascular death (HR: 1.53, 95% CI: 1.12-2.10) was observed for those
      with PAD compared with those without PAD. PAD was not associated with incident
      stroke. The association between PAD and hospitalization for HF was limited to
      participants with prior history of HF hospitalization (n = 2449; HR: 1.51, 95%
      CI: 1.09-2.13). CONCLUSIONS: PAD increases the risk for adverse outcomes in HFpEF
      and is associated with HF rehospitalization. Practitioners should be aware of the
      inherent risk associated with PAD in HFpEF.

PMID- 28444996
TI  - Breast arterial calcification association with coronary artery calcium scoring
      and implications for cardiovascular risk assessment in women.
AB  - Breast arterial calcification (BAC) is a type of medial artery calcification that
      can be seen incidentally on mammography. Studies have suggested association of
      BAC with cardiovascular risk factors, coronary artery disease (CAD), and
      cardiovascular morbidity and mortality. Recently published studies have also
      suggested a modest correlation of BAC with coronary artery calcium (CAC) scoring.
      Roughly 40 million mammograms are already performed annually in the United States
      with overlap in patients that undergo CAD screening via CAC scoring. Thus,
      identification of cardiovascular risk by demonstrating an association between BAC
      and CAC may enable an instrumental sex-specific methodology to identify
      asymptomatic women at risk for CAD. The purpose of this article is to review the
      current state of the literature for BAC and its association with CAC, to review
      contemporary breast cancer screening guidelines, and to discuss the clinical
      implications of these findings.

PMID- 28444997
TI  - A holistic view of the effects of episiotomy on pelvic floor.
AB  - Vaginal delivery is commonly accepted as a risk factor in pelvic floor
      dysfunction; however, other obstetric procedures (episiotomy) are still
      controversial. In this work, to analyze the relationship between episiotomy and
      pelvic floor function, a finite element model of the pelvic cavity is used
      considering the pelvic floor muscles (PFMs) with damaged regions from spontaneous
      vaginal delivery and from deliveries with episiotomy. Common features assessed at
      screening of pelvic floor dysfunction are evaluated during numerical simulations
      of both Valsalva maneuver and contraction. As stated in literature, a weakening
      of the PFM, represented by damaged regions in the finite element model, would
      lead to a bladder neck hypermobility measured as a variation between the alpha
      angle (angle between the bladder neck and the symphysis pubis line and the
      midline of the symphysis) during straining and withholding. However, the present
      work does not associate bladder neck hypermobility to a more damaged muscle,
      suggesting that other supportive structures also play an important role in the
      stabilization of the pelvic organs. Furthermore, considering passive behavior of
      the PFM, independently of the amount of damage considered, the resultant
      displacements of the pelvic structures are the same. Regarding the PFM
      contraction, the less the muscle is damaged, the greater the movements of the
      pelvic organs. Furthermore, the internal organs of the female genital system are
      the most affected by the unhealthy of the PFM. Additionally, the present study
      shows that the muscle damage affects more the active muscle component than the
      passive.

PMID- 28444999
TI  - Recent Publications of Interest.

PMID- 28444998
TI  - Large population cell characterization using quantitative phase cytometer.
AB  - A major challenge in cellular analysis is the phenotypic characterization of
      large cell populations within a short period of time. Among various parameters
      for cell characterization, the cell dry mass is often used to describe cell size
      but is difficult to be measured directly with traditional techniques. Here, we
      propose an interferometric approach based on line-focused beam illumination for
      high-content precision dry mass measurements of adherent cells in a non-invasive
      fashion-we call it quantitative phase cytometry (QPC). Besides dry mass, abundant
      cellular morphological features such as projected area, sphericity, and phase
      skewness can be readily extracted from the QPC interferometric data. To validate
      the utility of our technique, we demonstrate characterizing a large population of
      ~104 HeLa cells. Our reported QPC system is envisioned as a promising
      quantitative tool for label-free characterization of a large cell count at single
      cell resolution. (c) 2017 International Society for Advancement of Cytometry.

PMID- 28445000
TI  - Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a
      collaborative study including 416 sites.
AB  - Most studies assessing vegetation response following control of invasive Tamarix
      trees along southwestern U.S. rivers have been small in scale (e.g., river
      reach), or at a regional scale but with poor spatial-temporal replication, and
      most have not included testing the effects of a now widely used biological
      control. We monitored plant composition following Tamarix control along
      hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites
      across six U.S. states. This represents the largest comprehensive assessment to
      date on the vegetation response to the four most common Tamarix control
      treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the
      abundance of Tamarix less than active removal by mechanically using hand and
      chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also
      decreased with lower temperatures, higher precipitation, and follow-up treatments
      for Tamarix resprouting. Native cover generally increased over time in active
      Tamarix removal sites, however, the increases observed were small and was not
      consistently increased by active revegetation. Overall, native cover was
      correlated to permanent stream flow, lower grazing pressure, lower soil salinity
      and temperatures, and higher precipitation. Species diversity also increased
      where Tamarix was removed. However, Tamarix treatments, especially those
      generating the highest disturbance (burning and heavy machinery), also often
      promoted secondary invasions of exotic forbs. The abundance of hydrophytic
      species was much lower in treated than in reference sites, suggesting that
      management of southwestern U.S. rivers has focused too much on weed control,
      overlooking restoration of fluvial processes that provide habitat for hydrophytic
      and floodplain vegetation. These results can help inform future management of
      Tamarix-infested rivers to restore hydrogeomorphic processes, increase native
      biodiversity and reduce abundance of noxious species.

PMID- 28445001
TI  - Inhibition properties of some flavonoids on carbonic anhydrase I and II
      isoenzymes purified from human erythrocytes.
AB  - Carbonic anhydrases (CAs, E.C.4.2.1.1) play a critical role in many important
      physiological events and treatment of some diseases. Flavonoids or phenolic
      compounds have been discovered as novel CAs inhibitors instead of the traditional
      sulfonamides, with different binding to CAs, pro-drug activities, and new
      inhibition mechanisms. Here, we investigated the inhibition effects of some
      flavonoids including malvin, callistephin, oenin, pelargonin, silychristin, and 1
      (4-methoxyphenyl)-2-methyl-3-nitro-1-H-indol-6-ol (ID-8) against hCA I and II,
      which purified from human erythrocytes by affinity column chromatography. Both
      hCA isoenzymes were inhibited by flavonoids, with IC50 and Ki values in the range
      of 2.34 nM to 346.5 MUM and 51.01-99.55 MUM for hCA I and 86.60-750.00 MUM for
      hCA II, respectively. These results showed that flavonoids especially malvin and
      oenin effectively inhibited hCA I and II isoenzymes. Hence, they may be used as
      an effective CA inhibitor in medical applications for treatment of certain
      diseases such as glaucoma, in the future.

PMID- 28445003
TI  - A multiscale approach for determining the morphology of endothelial cells at a
      coronary artery.
AB  - The morphology of endothelial cells (ECs) may be an indication for determining
      atheroprone sites. Until now, there has been no clinical imaging technique to
      visualize the morphology of ECs in the arteries. The present study introduces a
      computational technique for determining the morphology of ECs. This technique is
      a multiscale simulation consisting of the artery scale and the cell scale. The
      artery scale is a fluid-structure interaction simulation. The input for the
      artery scale is the geometry of the coronary artery, that is, the dynamic
      curvature of the artery due to the cardiac motion, blood flow, blood pressure,
      heart rate, and the mechanical properties of the blood and the arterial wall, the
      measurements of which can be obtained for a specific patient. The results of the
      artery scale are wall shear stress (WSS) and cyclic strains as the mechanical
      stimuli of ECs. The cell scale is an inventive mass-and-spring model that is able
      to determine the morphological response of ECs to any combination of mechanical
      stimuli. The results of the multiscale simulation show the morphology of ECs at
      different locations of the coronary artery. The results indicate that the
      atheroprone sites have at least 1 of 3 factors: low time-averaged WSS, high angle
      of WSS, and high longitudinal strain. The most probable sites for atherosclerosis
      are located at the bifurcation region and lie on the myocardial side of the
      artery. The results also indicated that a higher dynamic curvature is a negative
      factor and a higher pulse pressure is a positive factor for protection against
      atherosclerosis.

PMID- 28445002
TI  - Glucose metabolism-targeted therapy and withaferin A are effective for epidermal
      growth factor receptor tyrosine kinase inhibitor-induced drug-tolerant
      persisters.
AB  - In pathway-targeted cancer drug therapies, the relatively rapid emergence of drug
      tolerant persisters (DTPs) substantially limits the overall therapeutic benefit.
      However, little is known about the roles of DTPs in drug resistance. In this
      study, we investigated the features of epidermal growth factor receptor-tyrosine
      kinase inhibitor-induced DTPs and explored a new treatment strategy to overcome
      the emergence of these DTPs. We used two EGFR-mutated lung adenocarcinoma cell
      lines, PC9 and II-18. They were treated with 2 MUM gefitinib for 6, 12, or 24
      days or 6 months. We analyzed the mRNA expression of the stem cell-related
      markers by quantitative RT-PCR and the expression of the cellular senescence
      associated proteins. Then we sorted DTPs according to the expression pattern of
      CD133 and analyzed the features of sorted cells. Finally, we tried to ablate DTPs
      by glucose metabolism targeting therapies and a stem-like cell targeting drug,
      withaferin A. Drug-tolerant persisters were composed of at least two types of
      cells, one with the properties of cancer stem-like cells (CSCs) and the other
      with the properties of therapy-induced senescent (TIS) cells. The CD133high cell
      population had CSC properties and the CD133low cell population had TIS
      properties. The CD133low cell population containing TIS cells showed a senescence
      associated secretory phenotype that supported the emergence of the CD133high cell
      population containing CSCs. Glucose metabolism inhibitors effectively eliminated
      the CD133low cell population. Withaferin A effectively eliminated the CD133high
      cell population. The combination of phloretin and withaferin A effectively
      suppressed gefitinib-resistant tumor growth.

PMID- 28445004
TI  - CFTR-dependent chloride efflux in cystic fibrosis mononuclear cells is increased
      by ivacaftor therapy.
AB  - AIM: The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) potentiator
      ivacaftor (Kalydeco(r)) improves clinical outcome in G551D cystic fibrosis (CF)
      patients. Here, we have investigated whether ivacaftor has a clinical impact on
      non-G551D gating mutations and function of circulating leukocytes as well.
      METHODS: Seven patients were treated with ivacaftor and evaluated at baseline,
      and at 1-3 and 6 months. Besides clinical and systemic inflammatory parameters,
      circulating mononuclear cells (MNC) were evaluated for CFTR-dependent chloride
      efflux by spectrofluorimetry, neutrophils for oxidative burst by cytofluorimetry
      and HVCN1 mRNA expression by real time PCR. RESULTS: Ivacaftor determined a
      significant decrease in sweat chloride concentrations at all time points during
      treatment. Body mass index (BMI), FEV1 , and FVC showed an increasing trend.
      While C-reactive protein decreased significantly at 2 months, the opposite
      behavior was noticed for circulating monocytes. CFTR activity in MNC was found to
      increase significantly at 3 and 6 months. Neutrophil oxidative burst peaked at 2
      months and then decreased to baseline. HVCN1 mRNA expression was significantly
      higher than baseline at 1-3 months and decreased after 6 months of treatment. The
      chloride efflux in MNC correlated positively with both FEV1 and FVC. On the other
      hand, sweat chloride correlated positively with CRP and WBC, and negatively with
      both respiratory function tests. A cluster analysis confirmed that sweat
      chloride, FEV1 , FVC, BMI, and MNC chloride efflux behaved as a single entity
      over time. DISCUSSION: In patients with non-G551D mutations, ivacaftor improved
      both chloride transport in sweat ducts and chloride efflux in MNC, that is,
      functions directly imputed to CFTR.

PMID- 28445005
TI  - Proteomic-based investigations on the mode of action of the marine anticancer
      compound rhizochalinin.
AB  - Rhizochalinin (Rhiz) is a novel marine natural sphingolipid-like compound, which
      shows promising in vitro and in vivo activity in human castration-resistant
      prostate cancer. In the present study, a global proteome screening approach was
      applied to investigate molecular targets and biological processes affected by
      Rhiz in castration-resistant prostate cancer. Bioinformatical analysis of the
      data predicted an antimigratory effect of Rhiz on cancer cells. Validation of
      proteins involved in the cancer-associated processes, including cell migration
      and invasion, revealed downregulation of specific isoforms of stathmin and LASP1,
      as well as upregulation of Grp75, keratin 81, and precursor IL-1beta by Rhiz.
      Functional analyses confirmed an antimigratory effect of Rhiz in PC-3 cells.
      Additionally, predicted ERK1/2 activation was confirmed by Western blotting
      analysis, and revealed prosurvival effects in Rhiz-treated prostate cancer cells
      indicating a potential mechanism of resistance. A combination of Rhiz with
      MEK/ERK inhibitors PD98059 (non-ATP competitive MEK1 inhibitor) and FR180204 (ATP
      competitive ERK1/2 inhibitor) resulted in synergistic effects. This work provides
      further insights into the molecular mechanisms underlying Rhiz bioactivity.
      Furthermore, our research is exemplary for the ability of proteomics to predict
      drug targets and mode of action of natural anticancer agents.

PMID- 28445007
TI  - Cobalt Phosphide Double-Shelled Nanocages: Broadband Light-Harvesting
      Nanostructures for Efficient Photothermal Therapy and Self-Powered
      Photoelectrochemical Biosensing.
AB  - Ultra-broadband light-absorbing materials are highly desired for effective solar
      energy harvesting. Herein, novel cobalt phosphide double-shelled nanocages (CoP
      NCs) are synthesized. Uniquely, these CoP-NCs are able to nonselectively absorb
      light spanning the full solar spectrum, benefiting from its electronic properties
      and hollow nanostructure. They promise a wide range of applications involving
      solar energy utilization. As proof-of-concept demonstrations, CoP-NCs are
      employed here as effective photothermal agents to ablate cancer cells by
      utilizing their ability of near-infrared heat conversion, and as photoactive
      material for self-powered photoelectrochemical sensing by taking advantage of
      their ability of photon-to-electricity conversion.

PMID- 28445006
TI  - Equine atypical myopathy in the UK: Epidemiological characteristics of cases
      reported from 2011 to 2015 and factors associated with survival.
AB  - BACKGROUND: Equine atypical myopathy (AM) is a toxic rhabdomyolysis associated
      with ingestion of hypoglycin A, derived typically in Europe, from Acer
      pseudoplatanus tree. Despite the wide distribution of this tree species in the
      UK, the number of cases reported annually varies, and there has been an apparent
      increase in prevalence in recent years. Although AM was first recognised in the
      UK, epidemiological studies have never been conducted focused solely on this
      country. OBJECTIVES: To describe the spatiotemporal distribution, presentation,
      treatment and outcome of AM cases reported in the UK. STUDY DESIGN: Retrospective
      case series. METHODS: British AM cases reported to the atypical myopathy alert
      website, between 2011 and 2015 were included (n = 224). Data were obtained via
      standardised epidemiological questionnaires from owners and veterinarians.
      Factors associated with survival were assessed using logistic regression.
      RESULTS: Most cases reported were from England (87.9%). Survival was 38.6% (n =
      73/189). Clinical factors associated with reduced odds of survival included,
      hypothermia (odds ratio [OR] 0.18; 95% confidence interval [CI] 0.06-0.57; P =
      0.01), bladder distension (OR 0.11; CI 0.02-0.59; P = 0.01), tachycardia (OR
      0.97; CI 0.94-0.99; P = 0.04) and serum creatine kinase activity >100,000 IU/L
      (OR 0.17; CI 0.04-0.68; P = 0.01) in the univariable analysis as well as
      recumbency. The latter was the only sign retained in multivariable analysis (OR =
      0.19; CI 0.06-0.62; P = 0.006). Administration of vitamins during the disease was
      associated with survival (OR 3.75; CI 1.21-11.57; P = 0.02). MAIN LIMITATIONS:
      Reporting cases to the Atypical Myopathy Alert Group is voluntary; therefore,
      under-reporting will result in underestimation of AM cases; furthermore, direct
      owner-reporting could have introduced misdiagnosis bias. CONCLUSION: Some areas
      of the UK reported AM cases more commonly. Clinical signs such as recumbency,
      rectal temperature, distended bladder and serum creatine kinase activity might be
      useful prognostic indicators though should be considered in the context of the
      clinical picture. Treatment with vitamins increases odds of survival.

PMID- 28445008
TI  - Prevalence of Complement-Mediated Cell Lysis-like Gene (sicG) in Streptococcus
      dysgalactiae subsp. equisimilis Isolates From Japan (2014-2016).
AB  - BACKGROUND: Streptococcus dysgalactiae subsp. equisimilis (SDSE; a beta-hemolytic
      streptococcus of human or animal origin) infections are emerging worldwide. We
      evaluated the clonal distribution of complement-mediated cell lysis-like gene
      (sicG) among SDSE isolates from three central prefectures of Japan. METHODS:
      Group G/C beta-hemolytic streptococci were collected from three institutions from
      April 2014 to March 2016. Fifty-five strains (52 from humans and three from
      animals) were identified as SDSE on the basis of 16S rRNA sequencing data.; they
      were obtained from 25 sterile (blood, joint fluid, and cerebrospinal fluid) and
      30 non-sterile (skin-, respiratory tract-, and genitourinary tract-origin)
      samples. emm genotyping, multilocus sequence typing, sicG
      amplification/sequencing, and random amplified polymorphic DNA (RAPD) analysis of
      sicG-positive strains were performed. RESULTS: sicG was detected in 30.9% of the
      isolates (16 human and one canine) and the genes from the 16 human samples
      (blood, 10; open pus, 3; sputum, 2; throat swab, 1) and one canine sample (open
      pus) showed the same sequence pattern. All sicG-harboring isolates belonged to
      clonal complex (CC) 17, and the most prevalent emm type was stG6792 (82.4%).
      There was a significant association between sicG presence and the development of
      skin/soft tissue infections. CC17 isolates with sicG could be divided into three
      subtypes by RAPD analysis. CONCLUSIONS: CC17 SDSE harboring sicG might have
      spread into three closely-related prefectures in central Japan during 2014-2016.
      Clonal analysis of isolates from other areas might be needed to monitor
      potentially virulent strains in humans and animals.

PMID- 28445009
TI  - Evaluation of Six Phenotypic Methods for the Detection of Carbapenemases in Gram
      Negative Bacteria With Characterized Resistance Mechanisms.
AB  - BACKGROUND: We compared the performance of the modified Hodge test (MHT), Triton
      Hodge test (THT), Carba NP test (CNPt), simplified Carba NP test (CNPt-direct),
      blue-Carba NP test (BCT), and carbapenem inactivation method (CIM) for rapid and
      accurate carbapenemase detection. METHODS: The methods were evaluated by using
      256 gram-negative isolates, including 197 Enterobacteriaceae (79 Enterobacter
      spp., 74 Klebsiella spp., 33 Escherichia coli, 10 Citrobacter spp., and 1
      Serratia marcescens), 51 Acinetobacter baumannii, and 8 Pseudomonas aeruginosa
      strains. The collection included 117 non-carbapenemase, 18 Klebsiella pneumoniae
      carbapenemases (KPC) producers, 46 New Delhi metallo-beta-lactamases (NDM)
      producers, 11 imipenemases (IMP) producers, and 51 oxacillinases (OXA) producers,
      and 13 strains harboring two different carbapenemase genes. RESULTS: The
      specificity of the THT (91.5%) was significantly lower than other methods, each
      of which had 100% specificity (P<0.003). This can be attributed to the false
      detection of Ampler class C beta-lactamases (AmpC) carriers. The CNPt-direct and
      CIM yielded the highest sensitivities (P<0.003), which were comparable (92.8% vs
      93.5%, P>0.999). Because of improved detection of NDM carriers, THT showed
      significantly higher sensitivity than the MHT (84.9% vs 75.5%, P<0.001). However,
      poor performances in detecting OXA still influenced the sensitivities of the CNPt
      (66.2%) and BCT (82.0%), as well as the MHT and THT. CONCLUSIONS: CNPt-direct and
      CIM demonstrated the best performance for the efficient detection of
      carbapenemase among the six evaluated methods. Except the MHT and THT, the
      detection of carbapenemase-producing Enterobacteriaceae by all the other methods
      was acceptable, when the OXA-type carbapenemase was not prevalent.

PMID- 28445010
TI  - Detection of Serum Antibodies to Hepatitis E Virus Based on HEV Genotype 3 ORF2
      Capsid Protein Expressed in Nicotiana benthamiana.
AB  - BACKGROUND: Hepatitis E virus (HEV) causes epidemics in developing countries and
      is primarily transmitted through the fecal-oral route. There have been recent
      reports on the zoonotic spread of the virus, and several animal species,
      primarily pigs, have been recognized as reservoirs of HEV. Because of its
      possible spread, there is an urgent need of a method for the cost-effective
      production of HEV proteins that can be used as diagnostic antigens for the
      serological detection of anti-HEV antibodies. METHODS: The HEV open reading frame
      (ORF)2 protein was purified from plant tissue by using immobilized metal-anion
      chromatography (IMAC). The recombinant protein was used to develop an in-house
      ELISA for testing anti-HEV antibodies in both human and swine sera. Thirty-six
      serum samples collected from patients with serologically proven HEV infection
      with commercial kits were tested for anti-HEV IgG antibodies by using the plant
      expressed protein. Forty-five serum samples collected from apparently healthy
      pigs in Bulgarian farms were also tested. RESULTS: We confirmed the transient
      expression and purification of a truncated version of the HEV genotype 3 capsid
      protein in Nicotiana benthamiana and its usefulness as a diagnostic antigen.
      ELISA showed the presence of anti-HEV IgG antibodies in 29 of the 36 human
      samples. The in-house ELISA showed anti-HEV IgG antibodies in 34 of the 45 pigs.
      CONCLUSIONS: We describe a method for the production of HEV ORF2 protein in N.
      benthamiana and the usefulness of this protein for the serological detection of
      anti-HEV antibodies in both humans and swine.

PMID- 28445011
TI  - Rapid Detection of Staphylococcus aureus and Methicillin-Resistant S. aureus in
      Atopic Dermatitis by Using the BD Max StaphSR Assay.
AB  - Eczematous lesions of atopic dermatitis (AD) patients are known to be a source of
      Staphylococcus aureus (SA) transmission and might be a reservoir for community
      associated methicillin-resistant SA (MRSA). The BD Max StaphSR (BD-SR) is a fully
      automated, multiplex real-time PCR assay for the direct detection and
      differentiation of SA and MRSA from nasal swab samples. We evaluated the
      detection rates of SA and MRSA from skin lesions of outpatients with AD using the
      BD-SR assay, and determined the usefulness of the BD-SR assay. A total of 244
      skin swab samples (skin lesions of 213 outpatients with AD and normal skin of 31
      healthy controls) were tested directly by using the BD-SR assay. Of the 213
      samples from patients with AD, 69 (32.4%) were positive for SA, 6 (8.7%) of which
      were positive for MRSA. Only 1 (3.2%) of 31 samples from healthy controls was
      positive for SA. The BD-SR assay is effective for the rapid detection of SA and
      MRSA from skin swab samples, which can provide important information for managing
      patients with AD and preventing the spread of MRSA.

PMID- 28445012
TI  - Drug Resistance Patterns of Multidrug- and Extensively Drug-Resistant
      Tuberculosis in Korea: Amplification of Resistance to Oral Second-line Drugs.
AB  - We aimed to analyze the drug resistance patterns of multidrug-resistant and
      extensively drug-resistant tuberculosis (TB) and the difference of drug
      resistance among various settings for health care in Korea. The data of drug
      susceptibility testing in 2009 was analyzed in order to secure sufficient number
      of patients from various settings in Korea. Patients were categorized by types of
      institutions into four groups, which comprised new and previously treated
      patients from public health care centers (PHC), the private sector, and Double
      barred Cross clinics (DBC). The resistance rates to first-line drugs were
      uniformly high in every group. While the resistance rates to second-line drugs
      were not as high as first-line drugs, there was a pattern that drug resistance
      rates were lowest for PHC and highest for DBC. The differences of the resistance
      rates were more prominent for oral second-line drugs. Our findings implied that
      drug resistance to oral second-line drugs was significantly amplified during
      multidrug-resistant-TB treatment in Korea. Therefore, an individualized approach
      is recommended for treating drug-resistant-TB based on susceptibility testing
      results to prevent acquisition or amplification of drug resistance.

PMID- 28445013
TI  - Comparison of Two Apheresis Systems of COBE and Optia for Autologous Peripheral
      Blood Stem Cell Collection.
AB  - Peripheral blood stem cell (PBSC) transplantation following myeloablative therapy
      is a mainstay of treatment for various types of malignancies. This study aimed to
      evaluate the differences between the Optia MNC and COBE Spectra MNC systems
      (Terumo BCT, Japan) according to apheresis procedures and the parameters of
      apheresis, products, and collection. The clinical data of 74 patients who
      underwent autologous PBSC collection from July 2012 to July 2015 were reviewed
      retrospectively. The patients comprised 48 (65%) men and 26 (35%) women with a
      median age of 56 yr (range, 23-66 yr). Of 216 procedures, 111 (51%) and 105 (49%)
      were processed by using COBE and Optia MNC, respectively. PBSC collection rates,
      throughput, numbers of stem cells retrieved, collection efficacy, and platelet
      loss were compared. There were no significant differences in the median CD34+
      cell counts of collected products (0.61*108 vs 0.94*108), CD34 collection
      efficiency (43.5% vs 42.1%), and loss of platelets (40.1% vs 44.7%). The Spectra
      Optia MNC apheresis system was comparable to the COBE Spectra system in
      collecting autologous CD34+ hematopoietic stem cells and retention of platelets.

PMID- 28445014
TI  - Detection of Immunoglobulin Heavy Chain Gene Clonality by Next-Generation
      Sequencing for Minimal Residual Disease Monitoring in B-Lymphoblastic Leukemia.
AB  - Minimal residual disease (MRD) following B-lymphoblastic leukemia (B-ALL)
      treatment has gained prognostic importance. Clonal immunoglobulin heavy chain
      (IGH) gene rearrangement is a useful follow-up marker in B-ALL owing to its high
      positivity rate. We evaluated the performance and clinical applicability of a
      next-generation sequencing (NGS) assay for IGH rearrangement in B-ALL MRD
      monitoring. IGH rearrangement was tested by using fluorescence PCR-fragment
      analysis and the NGS assay in eight B-ALL patients. The NGS assay was run on two
      platforms: the Ion Torrent PGM (Thermo Fisher Scientific, USA) (18 samples from
      1st to 7th patients) and the MiSeq system (Illumina, USA) (four samples from 8th
      patient). All initial diagnostic samples and four follow-up samples were positive
      for clonal IGH rearrangement with fluorescence PCR-fragment analysis and the NGS
      assay, and six follow-up samples were positive only with NGS. In one case with
      BCR-ABL1 translocation, BCR-ABL1 quantitative PCR was negative but the NGS IGH
      assay was positive just prior to full-blown relapse, suggesting the high
      sensitivity and clinical utility of the NGS assay. The NGS assay is proposed for
      MRD monitoring in B-ALL Additional studies are needed to confirm the clinical
      implications of cases showing positive results only in NGS.

PMID- 28445015
TI  - A Case of Acute Myeloid Leukemia Concurrent With Untreated Chronic Lymphocytic
      Leukemia.

PMID- 28445016
TI  - Sigma-Metrics of Electrolyte Tests From a Recently Launched New-Generation
      Proficiency Testing Program of the Korean Association of Quality Assurance for
      Clinical Laboratory.

PMID- 28445017
TI  - Toward Better Predictions of Chemosensitivity: Comparative Study of Conventional
      and Simulated Chemosensitivity Tests for Bladder Cancer Cell Lines.

PMID- 28445018
TI  - First Case of Skin and Soft Tissue Infection Caused by Mycoplasma hominis in a
      Pediatric Immunocompromised Patient.

PMID- 28445019
TI  - Robinsoniella peoriensis Bacteremia: a Second Case in Korea.

PMID- 28445020
TI  - Hemoglobin Kansas: First Korean Family and Literature Review.

PMID- 28445021
TI  - Homozygous LPL p.Gly188Glu Mutation in a Mexican Girl With Lipoprotein Lipase
      Deficiency.

PMID- 28445022
TI  - Novel Mutation (c.8725T>C) in Two Siblings With Late-Onset LAMA2-Related Muscular
      Dystrophy.

PMID- 28445023
TI  - Development and Application of a Laboratory-Developed Quality Control Program for
      Blood Glucose Monitoring Systems: A Single Institute Experience.

PMID- 28445024
TI  - An economic evaluation of the Enhanced Recovery After Surgery (ERAS) multisite
      implementation program for colorectal surgery in Alberta
AB  - BACKGROUND: In February 2013, Alberta Health Services established an Enhanced
      Recovery After Surgery (ERAS) implementation program for adopting the ERAS
      Society colorectal guidelines into 6 sites (initial phase) that perform more than
      75% of all colorectal surgeries in the province. We conducted an economic
      evaluation of this initiative to not only determine its cost-effectiveness, but
      also to inform strategy for the spread and scale of ERAS to other surgical
      protocols and sites. METHODS: We assessed the impact of ERAS on patients&#8217;
      health services utilization (HSU; length of stay [LOS], readmissions, emergency
      department visits, general practitioner and specialist visits) within 30 days of
      discharge by comparing pre- and post-ERAS groups using multilevel negative
      binomial regressions. We estimated the net health care costs/savings and the
      return on investment (ROI) associated with those impacts for post-ERAS patients
      using a decision analytic modelling technique. RESULTS: We included 331 pre- and
      1295 post-ERAS patients in our analyses. ERAS was associated with a reduction in
      all HSU outcomes except visits to specialists. However, only the reduction in
      primary LOS was significant. The net health system savings were estimated at $2
      290 000 (range $1 191 000&#8211;$3 391 000), or $1768 (range $920&#8211;$2619)
      per patient. The probability for the program to be cost-saving was 73%&#8211;83%.
      In terms of ROI, every $1 invested in ERAS would bring $3.8 (range
      $2.4&#8211;$5.1) in return. CONCLUSION: The initial phase of ERAS implementation
      for colorectal surgery in Alberta is cost-saving. The total savings has the
      potential to be more substantial when ERAS is spread for other surgical protocols
      and across additional sites.

PMID- 28445026
TI  - Chromium Poisoning Effects on Surface Exchange Kinetics of La0.6Sr0.4Co0.2Fe0.8O3
      delta.
AB  - The presence of Cr has already been reported in literature to cause severe
      degradation to La0.6Sr0.4Co0.2Fe0.8O3-delta (LSCF). However, fundamental
      understanding of Cr effects on the surface exchange kinetics is still lacking.
      For the first time, in situ gas phase isotopic oxygen exchange was utilized to
      quantitatively determine Cr effect on oxygen exchange kinetics of LSCF powder as
      a function of temperature and water vapor. Our investigations revealed that the
      formation of secondary phases such as SrCrO4, Cr2O3, Cr-Co-Fe-O, and La-Co-Fe-O
      can affect both the oxygen dissociation step and overall surface exchange.
      Specifically, Cr-containing secondary phases on the surface not only decrease the
      active sites for surface reactions but also alter the nearby stoichiometry of the
      LSCF matrix, thereby limiting surface oxygen transport. In addition, water
      molecules actively participate in the surface reactions and can further block the
      active sites.

PMID- 28445028
TI  - Enhanced Electrocatalytic Activity of Ethanol Oxidation Reaction on Palladium
      Silver Nanoparticles via Removable Surface Ligands.
AB  - This work developed a facile colloidal route to synthesize BH4--capped PdxAgy
      nanoparticles (NPs) in water using the reducing ionic liquids of [Cnmim]BH4, and
      the resulting NPs were prone to form the nanocomposites with [amim]+-modified
      reduced graphene (RG). The removal of the metal-free inorganic ions of BH4- can
      create the profoundly exposed interfaces on the PdxAgy NPs during the
      electrooxidation, and favor the ethanol oxidation reaction (EOR) in lowering
      energy barrier. The counterions of [Cnmim]+ can gather ethanol, OH- ions, and the
      reaction intermediates on catalysts, and synergistically interact with RG to
      facilitate the charge transfer in nanocomposites. The interface-modified RG
      nanosheets can effectively segregate the PdxAgy NPs from aggregation during the
      EOR. Along with the small size of 4.7 nm, the high alloying degree of 60.2%, the
      large electrochemical active surface area of 64.1 m2 g-1, and the great peak
      current density of 1501 mA cm-2 mg-1, Pd1Ag2@[C2mim]BH4-amimRG nanocomposite
      exhibits the low oxidation potentials, strong poison resistance, and stable
      catalytic activity for EOR in alkaline media, and hence can be employed as a
      promising anodic catalyst in ethanol fuel cells.

PMID- 28445027
TI  - Structurally Linked Dynamics in Lactate Dehydrogenases of Evolutionarily Distinct
      Species.
AB  - We present new findings about how primary and secondary structure affects the
      role of fast protein motions in the reaction coordinates of enzymatic reactions.
      Using transition path sampling and committor distribution analysis, we examined
      the difference in the role of these fast protein motions in the reaction
      coordinate of lactate dehydrogenases (LDHs) of Apicomplexa organisms Plasmodium
      falciparum and Cryptosporidium parvum. Having evolved separately from a common
      malate dehydrogenase ancestor, the two enzymes exhibit several important
      structural differences, notably a five-amino acid insertion in the active site
      loop of P. falciparum LDH. We find that these active site differences between the
      two organisms' LDHs likely cause a decrease in the contribution of the previously
      determined LDH rate-promoting vibration to the reaction coordinate of P.
      falciparum LDH compared to that of C. parvum LDH, specifically in the coupling of
      the rate-promoting vibration and the hydride transfer. This effect, while subtle,
      directly shows how changes in structure near the active site of LDH alter
      catalytically important motions. Insights provided by studying these alterations
      would prove to be useful in identifying LDH inhibitors that specifically target
      the isozymes of these parasitic organisms.

PMID- 28445029
TI  - NHS-Esters As Versatile Reactivity-Based Probes for Mapping Proteome-Wide
      Ligandable Hotspots.
AB  - Most of the proteome is considered undruggable, oftentimes hindering
      translational efforts for drug discovery. Identifying previously unknown
      druggable hotspots in proteins would enable strategies for pharmacologically
      interrogating these sites with small molecules. Activity-based protein profiling
      (ABPP) has arisen as a powerful chemoproteomic strategy that uses reactivity
      based chemical probes to map reactive, functional, and ligandable hotspots in
      complex proteomes, which has enabled inhibitor discovery against various
      therapeutic protein targets. Here, we report an alkyne-functionalized N
      hydroxysuccinimide-ester (NHS-ester) as a versatile reactivity-based probe for
      mapping the reactivity of a wide range of nucleophilic ligandable hotspots,
      including lysines, serines, threonines, and tyrosines, encompassing active sites,
      allosteric sites, post-translational modification sites, protein interaction
      sites, and previously uncharacterized potential binding sites. Surprisingly, we
      also show that fragment-based NHS-ester ligands can be made to confer selectivity
      for specific lysine hotspots on specific targets including Dpyd, Aldh2, and
      Gstt1. We thus put forth NHS-esters as promising reactivity-based probes and
      chemical scaffolds for covalent ligand discovery.

PMID- 28445030
TI  - Synthesis of Aminofuran-Linked Benzimidazoles and Cyanopyrrole-Fused
      Benzimidazoles by Condition-Based Skeletal Divergence.
AB  - A condition-based skeletal divergent synthesis was explored to achieve skeletal
      diversity in two component condensation reaction. Cyanomethyl benzimidazole was
      reacted with alpha-bromoketone under thermal conditions to furnish 2-aminofuranyl
      benzimidazoles, while the same reaction afforded 3-cyano-benzopyrrolo-imidazoles
      under microwave irradiation. Two nonequivalent nucleophilic centers on
      benzimidazole moiety were manipulated elegantly by different reaction conditions
      to achieve the skeletal diversity.

PMID- 28445031
TI  - Importance of Loop L1 Dynamics for Substrate Capture and Catalysis in Pseudomonas
      aeruginosa d-Arginine Dehydrogenase.
AB  - Mobile loops located at the active site entrance in enzymes often participate in
      conformational changes required to shield the reaction from bulk solvent, to
      control the access of the substrate to the active site, and to position residues
      for substrate binding and catalysis. In d-arginine dehydrogenase from Pseudomonas
      aeruginosa (PaDADH), previous crystallographic data suggested that residues 45-47
      in the FAD-binding domain and residues 50-56 in the substrate-binding domain in
      loop L1 could adopt two distinct conformations. In this study, we have used
      molecular dynamics, kinetics, and fluorescence spectroscopy on the S45A and A46G
      enzyme variants of PaDADH to investigate the impact of mutations in loop L1 on
      the catalytic function of the enzyme. Molecular dynamics showed that the mutant
      enzymes have probabilities of being in open conformations that are higher than
      that of wild-type PaDADH of loop L1, yielding an increased level of solvent
      exposure of the active site. In agreement, the flavin fluorescence intensity was
      ~2-fold higher in the S45A and A46G enzymes than in wild-type PaDADH, with a 9 nm
      bathochromic shift of the emission band. In the variant enzymes, the kcat/Km
      values with d-arginine were ~13-fold lower than in wild-type PaDADH. Moreover,
      the pH profiles for the kcat value with d-arginine showed a hollow, consistent
      with restricted proton movements in catalysis, and no saturation was achieved
      with the alternate substrate d-leucine in the reductive half-reaction of the
      variant enzymes. Taken together, the computational and experimental data are
      consistent with the dynamics of loop L1 being important for substrate capture and
      catalysis in PaDADH.

PMID- 28445032
TI  - Superstretchable Nacre-Mimetic Graphene/Poly(vinyl alcohol) Composite Film Based
      on Interfacial Architectural Engineering.
AB  - Through designing hierarchical structures, particularly optimizing the chemical
      and architectural interactions at its inorganic/organic interface, nacre has
      achieved an excellent combination of contradictory mechanical properties such as
      strength and toughness, which is highly demanded yet difficult to achieve by most
      synthetic materials. Most techniques applied to develop nacre-mimetic composites
      have been focused on mimicking the "brick-and-mortar" structure, but the
      interfacial architectural features, especially the asperities and mineral bridges
      of "bricks", have been rarely concerned, which are of equal importance for
      enhancing mechanical properties of nacre. Here, we used a modified bidirectional
      freezing method followed by uniaxial pressing and chemical reduction to assemble
      a nacre-mimetic graphene/poly(vinyl alcohol) composite film, with both asperities
      and bridges introduced in addition to the lamellar layers to mimic the
      interfacial architectural interactions found in nacre. As such, we have developed
      a composite film that is not only strong (up to ~150.9 MPa), but also tough (up
      to ~8.50 MJ/m3), and highly stretchable (up to ~10.44%), difficult to obtain by
      other methods. This was all achieved by only interfacial architectural
      engineering within the traditional "brick-and-mortar" structure, without
      introducing a third component or employing chemical cross-linker as in some other
      nacre-mimetic systems. More importantly, we believe that the design principles
      and processing strategies reported here can also be applied to other material
      systems to develop strong and stretchable materials.

PMID- 28445033
TI  - C-H Functionalization of Azines.
AB  - Azines, which are six-membered aromatic compounds containing one or more nitrogen
      atoms, serve as ubiquitous structural cores of aromatic species with important
      applications in biological and materials sciences. Among a variety of synthetic
      approaches toward azines, C-H functionalization represents the most rapid and
      atom-economical transformation, and it is advantageous for the late-stage
      functionalization of azine-containing functional molecules. Since azines have
      several C-H bonds with different reactivities, the development of new reactions
      that allow for the functionalization of azines in a regioselective fashion has
      comprised a central issue. This review describes recent advances in the C-H
      functionalization of azines categorized as follows: (1) SNAr reactions, (2)
      radical reactions, (3) deprotonation/functionalization, and (4) metal-catalyzed
      reactions.

PMID- 28445034
TI  - Dual In-Tether Chiral Centers Modulate Peptide Helicity.
AB  - The facile chemical modification on the peptide cross-linking moiety is an
      important strategy for improving the physicochemical properties of a peptide.
      Herein, peptides were constrained into helical conformations via the synergistic
      effects of dual in-tether chiral centers. A pentapeptide minimalistic model was
      used to determine the correlation between the absolute configurations of the dual
      in-tether chiral centers and the secondary structures of the peptides. This
      strategy provides an on-tether modification site that does not interrupt the
      secondary structure of the peptide.

PMID- 28445035
TI  - Characteristics of Reduced Graphene Oxide Quantum Dots for a Flexible Memory Thin
      Film Transistor.
AB  - Reduced graphene oxide quantum dot (rGOQD) devices in formats of capacitor and
      thin film transistor (TFT) were demonstrated and examined as the first trial to
      achieve nonambipolar channel property. In addition, through a gold nanoparticle
      (Au NP) layer embedded between the rGOQD active channel and dielectric layer,
      memory capacitor and TFT performances were realized by capacitance-voltage (C-V)
      hysteresis and gate program, erase, and reprogram biases. First, capacitor
      structure of the rGOQD memory device was constructed to examine memory charging
      effect featured in hysteretic C-V behavior with a 30 nm dielectric layer of cross
      linked poly(vinyl alcohol). For the intervening Au NP charging layer, self
      assembled monolayer (SAM) formation of the Au NP was executed to utilize
      electrostatic interaction by a dip-coating process under ambient environments
      with a conformal fabrication uniformity. Second, the rGOQD memory TFT device was
      also constructed in the same format of the Au NPs SAMs on a flexible substrate.
      Characteristics of the rGOQD TFT output showed novel saturation curves unlike
      typical graphene-based TFTs. However, The rGOQD TFT device reveals relatively low
      on/off ratio of 101 and mobility of 5.005 cm2/V.s. For the memory capacitor, the
      flat-band voltage shift (DeltaVFB) was measured as 3.74 V for +/-10 V sweep, and
      for the memory TFT, the threshold voltage shift (DeltaVth) by the Au NP charging
      was detected as 7.84 V. In summary, it was concluded that the rGOQD memory device
      could accomplish an ideal graphene-based memory performance, which could have
      provided a wide memory window and saturated output characteristics.

PMID- 28445036
TI  - Silver Nanoparticles and Wheat Roots: A Complex Interplay.
AB  - Agricultural soils are major sinks of silver nanoparticles in the environment,
      and crops are directly exposed to these emerging contaminants. A clear picture of
      their chemical transformations, uptake and transport mechanisms, and phytotoxic
      impacts is still lacking. In this work, wheat plants were exposed to pristine
      metallic (Ag-NPs) and sulfidized (Ag2S-NPs) silver nanoparticles and ionic Ag.
      Data on Ag distribution and speciation, phytotoxicity markers, and gene
      expression were studied. A multi-technique and multi-scale approach was applied,
      combining innovating tools at both the laboratory and synchrotron. Various
      chemical transformations were observed on the epidermis and inside roots, even
      for Ag2S-NPs, leading to an exposure to multiple Ag forms, which likely evolve
      over time. Genes involved in various functions including oxidative stress,
      defense against pathogens, and metal homeostasis were impacted in different ways
      depending upon the Ag source. This study illustrates the complexity of the
      toxicity pattern for plants exposed to Ag-NPs, the necessity of monitoring
      several markers to accurately evaluate the toxicity, and the interest of
      interpreting the toxicity pattern in light of the distribution and speciation of
      Ag.

PMID- 28445037
TI  - Discovery of 5-Azaindazole (GNE-955) as a Potent Pan-Pim Inhibitor with Optimized
      Bioavailability.
AB  - Pim kinases have been identified as promising therapeutic targets for hematologic
      oncology indications, including multiple myeloma and certain leukemia. Here, we
      describe our continued efforts in optimizing a lead series by improving
      bioavailability while maintaining high inhibitory potency against all three Pim
      kinase isoforms. The discovery of extensive intestinal metabolism and major
      metabolites helped refine our design strategy, and we observed that optimizing
      the pharmacokinetic properties first and potency second was a more successful
      approach than the reverse. In the resulting work, novel analogs such as 20 (GNE
      955) were discovered bearing 5-azaindazole core with noncanonical hydrogen
      bonding to the hinge.

PMID- 28445038
TI  - Distinguishing Quinacridone Pigments via Terahertz Spectroscopy: Absorption
      Experiments and Solid-State Density Functional Theory Simulations.
AB  - Through a combined experimental and theoretical investigation we determine that
      the fundamental modes of three quinacridones fall in the terahertz spectral range
      (1-10 THz, ~30-300 cm-1). In each spectrum the terahertz resonances correspond to
      wagging, rocking, or twisting of the quinacridone rings, with the most intense
      absorption being an in-plane rocking vibration of the carbonyl oxygens. In spite
      of these spectral similarities, we demonstrate that terahertz measurements
      readily differentiate beta-quinacridone, gamma-quinacridone, and 2,9
      dimethylquinacridone. The spectrum of beta-quinacridone has a group of closely
      spaced modes at ~4 THz, whereas in contrast the spectrum of gamma-quinacridone
      displays a widely spaced series of modes spread over the range ~1-5 THz. Both of
      these have the strongest mode at ~9 THz, whereas in contrast 2,9
      dimethylquinacridone exhibits the strongest mode at ~7 THz. Because quinacridones
      are the basis of widely used synthetic pigments of relatively recent origin, our
      findings offer promising applications in the identification and dating of modern
      art.

PMID- 28445039
TI  - Tricyclic Polyprenylated Acylphloroglucinols from St John's Wort, Hypericum
      perforatum.
AB  - The new polyprenylated acylphloroglucinol derivatives 1-15 and the known
      furohyperforin (16) were isolated from the stems and leaves of Hypericum
      perforatum. Their structures were determined by analyses of NMR and HRESIMS data.
      Their absolute configurations were elucidated by a combination of electronic
      circular dichroism (ECD) and Rh2(OCOCF3)4-induced ECD, as well as X-ray
      diffraction crystallography. The new hyperforatin F (9) contains a unique acetyl
      functionality at C-1 of the bicyclo[3.3.1]nonane core. Hyperforatins G (10) and H
      (11) are similarly the first examples of naturally occurring [3.3.1]-type
      polycyclic prenylated acylphloroglucinols possessing a carbonyl functionality at
      C-32. The compounds were tested for their acetylcholinesterase (AChE) inhibitory
      activities and cytotoxic activities against a panel of human tumor cell lines.
      Compounds 3, 5, 6, 8, and 9 exerted moderate inhibitory activities (IC50 3.98
      9.13 MUM) against AChE.

PMID- 28445040
TI  - Chemoenzymatic Total Synthesis of the Proposed Structures of Putaminoxins B and
      D.
AB  - Different enzymatic and nonenzymatic approaches were tested and compared to
      afford enantiopure homoallylic and allylic alcohols as building blocks in a total
      synthesis showcase. Thereby, highly enantioselective alcohol dehydrogenases and
      the P450 BM3 monooxygenase variant A74G L188Q were compared to classical
      asymmetric reagent-controlled allyl additions. Thus, the first total syntheses of
      the proposed structures for putaminoxins B/D and their respective enantiomers
      were accomplished. Detailed spectroscopic analysis of the newly synthesized
      compounds unraveled a discrepancy with respect to the reported structures of
      putaminoxins B/D. Furthermore, it was demonstrated that total synthesis is
      generally required for unequivocal assignment of configuration, because purely
      comparative NMR studies and judgment by analogy can lead to false predictions.

PMID- 28445041
TI  - Verbeekite, the Long-Unknown Crystal Structure of Monoclinic PdSe2.
AB  - Verbeekite, a monoclinic polymorph of PdSe2, was reported for the first time in
      2002 by Roberts et al. The mineral has been discovered in the Musonoi Cu-Co-Mn-U
      mine, Democratic Republic of Congo, and was named after Dr. Theodore Verbeek, the
      first geoscientist who studied the palladium mineralization there (1955-1967).
      Until today, the crystal structure of this very rare mineral has been unknown. By
      syntheses via multianvil high-pressure/high-temperature methods at 11.5 GPa and
      1300  degrees C, synthetic verbeekite could be obtained in a high degree of
      purity and comparatively good crystal quality, which made it possible to
      determine the full crystal structure for PdSe2 verbeekite from single-crystal X
      ray diffractometer data: I2/a, a = 671.0(2) pm, b = 415.42(8) pm, c = 891.4(2)
      pm, beta = 92.42(3) degrees , V = 248.24(4) A3, R1 = 0.0368, wR2 = 0.0907 (all
      data). In contrast to layered PdS2-type PdSe2, verbeekite exhibits a novel
      crystal structure type of dichalcogenides of the platinum-group metals with
      (Se2)2- dimer anions connecting the layers. The possibility of different
      arrangements of the characteristic (Se2)2- dumbbells is the reason for the
      various polymorphs of the dichalcogenides, with now five known PdSe2
      representatives.

PMID- 28445042
TI  - Structural Transformation of MnO2 during the Oxidation of Bisphenol A.
AB  - Bisphenol A (BPA) is an endocrine-disrupting compound widely used in the plastic
      industry and found in natural waters at concentrations considered harmful for
      aquatic life. BPA is susceptible to oxidation by Mn(III/IV) oxides, which are
      commonly found in near-surface environments. Here, we quantify BPA oxidation
      rates and the formation of its predominant product, 4-hydroxycumyl alcohol (HCA),
      in tandem with transformation of a synthetic, Mn(III)-rich delta-MnO2. To
      investigate the effect of Mn oxide structural changes on BPA oxidation rate, 12
      sequential additions of 80 MUM BPA are performed at pH 7. During the additions,
      BPA oxidation rate decreases by 3 orders of magnitude, and HCA yield decreases
      from 40% to 3%. This is attributed to the accumulation of interlayer Mn(II/III)
      produced during the reaction, as observed using X-ray absorption spectroscopy, as
      well as additional spectroscopic and wet chemical techniques. HCA is oxidized at
      a rate that is 12.6 times slower than BPA and accumulates in solution. These
      results demonstrate that BPA degradation by environmentally relevant Mn(III/IV)
      oxides is inhibited by the buildup of solid-phase Mn(II/III), specifically in
      interlayer sites. Nevertheless, Mn oxides may limit BPA migration in near-surface
      environments and have potential for use in drinking and wastewater treatment.

PMID- 28445043
TI  - Assembly of Effective Halide Receptors from Components. Comparing Hydrogen,
      Halogen, and Tetrel Bonds.
AB  - Receptors for halide anions are constructed based on the imidazolium unit and
      then replacing the H-bonding C-H group first by halogen-bonding C-I and then by
      tetrel-bonding C-SnH3 and C-SiF3. Attaching a phenyl ring to any of these species
      has little effect on its ability to bind a halide, but incorporation of a second
      imidazolium to the benzene connector, forming a bidentate dicationic receptor,
      greatly enhances the binding. Addition of electron-withdrawing F atoms to each
      imidazolium adds a further increment. F- consistently binds more strongly to the
      various receptor models than does Cl-. Whereas replacement of the H atom on the
      imidazolium groups with the halogen-bonding I has an inconsistent perturbing
      effect, tetrel-bonding SnH3 significantly enhances the binding with either
      halide, and SiF3 even more so. Placement of the various complexes into aqueous
      solution reduces binding energies but the trends that occur in the gas phase are
      largely reproduced in water. The tetrel-bonding receptors are the most selective
      for F- over Cl- with an equilibrium ratio on the order of 1014 for SnH3 and 1028
      for SiF3. When combined with their strong halide binding, SiF3-ImF3-Bz-ImF3
      SiF3+2 bipodal receptors represent an optimal choice in terms of both binding
      strength and selectivity.

PMID- 28445044
TI  - Highly Oxygenated Multifunctional Compounds in alpha-Pinene Secondary Organic
      Aerosol.
AB  - Highly oxygenated multifunctional organic compounds (HOMs) originating from
      biogenic emissions constitute a widespread source of organic aerosols in the
      pristine atmosphere. However, the molecular forms in which HOMs are present in
      the condensed phase upon gas-particle partitioning remain unclear. In this study,
      we show that highly oxygenated molecules that contain multiple peroxide
      functionalities are readily cationized by the attachment of Na+ during
      electrospray ionization operated in the positive ion mode. With this method, we
      present the first identification of HOMs characterized as C8-10H12-18O4-9
      monomers and C16-20H24-36O8-14 dimers in alpha-pinene derived secondary organic
      aerosol (SOA). Simultaneous detection of these molecules in the gas phase
      provides direct evidence for their gas-to-particle conversion. Molecular
      properties of particulate HOMs generated from ozonolysis and OH oxidation of
      unsubstituted (C10H16) and deuterated (C10H13D3) alpha-pinene are investigated
      using coupled ion mobility spectrometry with mass spectrometry. The systematic
      shift in the mass of monomers in the deuterated system is consistent with the
      decomposition of isomeric vinylhydroperoxides to release vinoxy radical
      isotopologues, the precursors to a sequence of autoxidation reactions that
      ultimately yield HOMs in the gas phase. The remarkable difference observed in the
      dimer abundance under O3- versus OH-dominant environments underlines the
      competition between intramolecular hydrogen migration of peroxy radicals and
      their bimolecular termination reactions. Our results provide new and direct
      molecular-level information for a key component needed for achieving carbon mass
      closure of alpha-pinene SOA.

PMID- 28445045
TI  - Intermediates and Reactivity in Iron-Catalyzed Cross-Couplings of Alkynyl
      Grignards with Alkyl Halides.
AB  - Iron-catalyzed cross-coupling reactions using alkynyl nucleophiles represent an
      attractive approach for the incorporation of alkynyl moieties into organic
      molecules. In the present study, a multitechnique approach combining inorganic
      spectroscopic methods, inorganic synthesis, and reaction studies is applied to
      iron-SciOPP catalyzed alkynyl-alkyl cross-couplings, providing the first detailed
      insight into the effects of variation from sp2- to sp-hybridized nucleophiles on
      iron speciation and reactivity. Reaction studies demonstrate that reaction of
      FeBr2(SciOPP) with 1 equiv (triisopropylsilyl)ethynylmagnesium bromide (TIPS-CC
      MgBr) leads to a distribution of mono-, bis-, and tris-alkynylated iron(II)
      SciOPP species due to rapid alkynyl ligand redistribution. While solvents such as
      THF promote these complex redistribution pathways, nonpolar solvents such as
      toluene enable increased stabilization of these iron species and further enabled
      assessment of their reactivity with electrophile. While the tris-alkynylated
      iron(II)-SciOPP species was found to be unreactive with the cycloheptyl bromide
      electrophile over the average turnover time of catalysis, the in situ formed
      neutral mono- and bis-alkynylated iron(II)-SciOPP complexes are consumed upon
      reaction with the electrophile with concomitant generation of cross-coupled
      product at catalytically relevant rates, indicating the ability of one or both of
      these species to react selectively with the electrophile. The nature of the
      reaction solvent and Grignard reagent addition rate were found to have broader
      implications in overall reaction selectivity, reaction rate, and accessibility of
      off-cycle iron(I)-SciOPP species. Additionally, the effects of steric
      substitution of the alkynyl Grignard reagent on catalytic performance were
      investigated. Fundamental insight into iron speciation and reactivity with
      alkynyl nucleophiles reported herein provides an essential foundation for the
      continued development of this important class of reactions.

PMID- 28445046
TI  - Lead Discovery of Dual G-Quadruplex Stabilizers and Poly(ADP-ribose) Polymerases
      (PARPs) Inhibitors: A New Avenue in Anticancer Treatment.
AB  - G-quadruplex stabilizers are an established opportunity in anticancer
      chemotherapy. To circumvent the antiproliferative effects of G4 ligands, cancer
      cells recruit PARP enzymes at telomeres. Herein, starting from the structural
      similarity of a potent G4 ligand previously discovered by our group and a
      congeneric PARP inhibitor, a library of derivatives was synthesized to discover
      the first dual G4/PARP ligand. We demonstrate that a properly decorated
      thieno[3,2-c]quinolin-4(5H)-one stabilizes the G4 fold in vitro and in cells,
      induces a DNA damage response localized to telomeres, inhibits PARylation in
      cells, and has an antiproliferative effect in BRCA2 deficient tumor cells.

PMID- 28445047
TI  - Development of Selective, Orally Active GPR4 Antagonists with Modulatory Effects
      on Nociception, Inflammation, and Angiogenesis.
AB  - A novel, selective, and efficacious GPR4 antagonist 13 was developed starting
      from lead compound 1a. While compound 1a showed promising efficacy in several
      disease models, its binding to a H3 receptor as well as a hERG channel prevented
      it from further development. Therefore, a new round of optimization addressing
      the key liabilities was performed and led to discovery of compound 13 with an
      improved profile. Compound 13 showed significant efficacy in the rat antigen
      induced arthritis as well as in the hyperalgesia and angiogenesis model at a well
      tolerated dose of 30 mg/kg.

PMID- 28445048
TI  - Molecularly Tailored Nickel Precursor and Support Yield a Stable Methane Dry
      Reforming Catalyst with Superior Metal Utilization.
AB  - Syngas production via the dry reforming of methane (DRM) is a highly endothermic
      process conducted under harsh conditions; hence, the main difficulty resides in
      generating stable catalysts. This can, in principle, be achieved by reducing coke
      formation, sintering, and loss of metal through diffusion in the support.
      [{Ni(MU2-OCHO)(OCHO)(tmeda)}2(MU2-OH2)] (tmeda = tetramethylethylenediamine),
      readily synthesized and soluble in a broad range of solvents, was developed as a
      molecular precursor to form 2 nm Ni(0) nanoparticles on alumina, the commonly
      used support in DRM. While such small nanoparticles prevent coke deposition and
      increase the initial activity, operando X-ray Absorption Near-Edge Structure
      (XANES) spectroscopy confirms that deactivation largely occurs through the
      migration of Ni into the support. However, we show that Ni loss into the support
      can be mitigated through the Mg-doping of alumina, thereby increasing
      significantly the stability for DRM. The superior performance of our catalytic
      system is a direct consequence of the molecular design of the metal precursor and
      the support, resulting in a maximization of the amount of accessible metallic
      nickel in the form of small nanoparticles while preventing coke deposition.

PMID- 28445049
TI  - Inflammation Modulatory Phorbol Esters from the Seeds of Aquilaria malaccensis.
AB  - The tree Aquilaria malaccensis is a valuable source of agarwood, which is used in
      herbal medicinal preparations. Phytochemical research on A. malaccensis seeds has
      led to the isolation of four new phorbol esters (1-4), two known phorbol esters
      (5, isolated from Nature for the first time, and 6), and two known glycerides (7
      and 8). The structures of these isolates were elucidated by means of
      spectroscopic data interpretation. The inflammation-modulatory activities of the
      isolates on elastase release and superoxide anion generation in human neutrophils
      were evaluated. Interestingly, phorbol esters 1, 5, and 6 showed potent
      inhibitory activity on elastase release in human neutrophils, with IC50 values of
      2.7, 0.8, and 2.1 MUM, respectively. All isolated phorbol esters exerted
      enhancing activity on superoxide anion generation. The results indicated that
      phorbol esters may play a bilateral modulatory role in the processes of
      inflammation. In addition, the compounds were evaluated for their cytotoxic
      properties against HepG2 (hepatoma), MDA-MB-231 (breast), and A549 (lung) cancer
      cells, but all compounds were inactive for all cell lines used (IC50 > 10 MUM).

PMID- 28445051
TI  - Potential Air Pollutant Emissions and Permitting Classifications for Two
      Biorefinery Process Designs in the United States.
AB  - Advanced biofuel production facilities (biorefineries), such as those envisioned
      by the United States (U.S.) Renewable Fuel Standard and U.S. Department of
      Energy's research and development programs, often lack historical air pollutant
      emissions data, which can pose challenges for obtaining air emission permits that
      are required for construction and operation. To help fill this knowledge gap, we
      perform a thorough regulatory analysis and use engineering process designs to
      assess the applicability of federal air regulations and quantify air pollutant
      emissions for two feasibility-level biorefinery designs. We find that without
      additional emission-control technologies both biorefineries would likely be
      required to obtain major source permits under the Clean Air Act's New Source
      Review program. The permitting classification (so-called "major" or "minor") has
      implications for the time and effort required for permitting and therefore
      affects the cost of capital and the fuel selling price. Consequently, we explore
      additional technically feasible emission-control technologies and process
      modifications that have the potential to reduce emissions to achieve a minor
      source permitting classification. Our analysis of air pollutant emissions and
      controls can assist biorefinery developers with the air permitting process and
      inform regulatory agencies about potential permitting pathways for novel
      biorefinery designs.

PMID- 28445050
TI  - Involvement of WRKY Transcription Factors in Abscisic-Acid-Induced Cold Tolerance
      of Banana Fruit.
AB  - Phytohormone abscisic acid (ABA) and plant-specific WRKY transcription factors
      (TFs) have been implicated to play important roles in various stress responses.
      The involvement of WRKY TFs in ABA-mediated cold tolerance of economical fruits,
      such as banana fruit, however remains largely unknown. Here, we reported that ABA
      application could induce expressions of ABA biosynthesis-related genes MaNCED1
      and MaNCED2, increase endogenous ABA contents, and thereby enhance cold tolerance
      in banana fruit. Four banana fruit WRKY TFs, designated as MaWRKY31, MaWRKY33,
      MaWRKY60, and MaWRKY71, were identified and characterized. All four of these
      MaWRKYs were nuclear-localized and displayed transactivation activities. Their
      expressions were induced by ABA treatment during cold storage. More importantly,
      the gel mobility shift assay and transient expression analysis revealed that
      MaWRKY31, MaWRKY33, MaWRKY60, and MaWRKY71 directly bound to the W-box elements
      in MaNCED1 and MaNCED2 promoters and activated their expressions. Taken together,
      our findings demonstrate that banana fruit WRKY TFs are involved in ABA-induced
      cold tolerance by, at least in part, increasing ABA levels via directly
      activating NECD expressions.

PMID- 28445052
TI  - Facile Preparation of Drug-Loaded Tristearin Encapsulated Superparamagnetic Iron
      Oxide Nanoparticles Using Coaxial Electrospray Processing.
AB  - Naturally occurring polymers are promising biocompatible materials that have many
      applications for emerging therapies, drug delivery systems, and diagnostic
      agents. The handling and processing of such materials still constitutes a major
      challenge, which can limit the full exploitation of their properties. This study
      explores an ambient environment processing technique: coaxial electrospray (CO
      ES) to encapsulate genistein (an isoflavonoid and model drug), superparamagnetic
      iron oxide nanoparticles (SPIONs, 10-15 nm), and a fluorophore (BODIPY) into a
      layered (triglyceride tristearin shell) particulate system, with a view to
      constructing a theranostic agent. Mode mapping of CO-ES led to an optimized
      atomization engineering window for stable jetting, leading to encapsulation of
      SPIONs within particles of diameter 0.65-1.2 MUm and drug encapsulation
      efficiencies of around 92%. Electron microscopy was used to image the
      encapsulated SPIONs and confirm core-shell triglyceride encapsulation in addition
      to further physicochemical characterization (AFM, FTIR, DSC, and TGA). Cell
      viability assays (MTT, HeLa cells) were used to determine optimal SPION loaded
      particles (~1 mg/mL), while in vitro release profile experiments (PBS, pH = 7.4)
      demonstrate a triphasic release profile. Further cell studies confirmed cell
      uptake and internalization at selected time points (t = 1, 2, and 4 h). The
      results suggest potential for using the CO-ES technique as an efficient way to
      encapsulate SPIONs together with sensitive drugs for the development of
      multimodal particles that have potential application for combined imaging and
      therapy.

PMID- 28445054
TI  - Catalytic Decomposition of NO by Cationic Platinum Oxide Cluster Pt3O4.
AB  - The catalytic decomposition of NO by cationic platinum oxide cluster Pt3O4+ was
      investigated by mass spectrometry and thermal desorption spectrometry. Upon
      reaction with two NO molecules, molecular oxygen desorbed from the cluster at
      room temperature to form Pt3O4N2+. Then, at temperatures above 400 K, desorption
      of N2 from Pt3O4N2+ was observed. These processes were confirmed by isotope
      labeling experiments, and the energetics of O2 and N2 release were determined by
      density functional calculations. The combination of these elementary steps
      resulted in the catalytic decomposition of NO by Pt3O4+.

PMID- 28445053
TI  - Sulfotransferases and Breast Cancer Resistance Protein Determine the Disposition
      of Calycosin in Vitro and in Vivo.
AB  - Sulfation is a key process of drug disposition that generally regulates drug
      effectiveness and toxicity. Calycosin derived from the dry root extract of Radix
      Astragali exhibits a variety of biological effects that easily undergo extensive
      phase II metabolism. However, the sulfation pathway of calycosin lacks
      information. We investigated the disposition mechanisms of calycosin sulfate in
      vitro and in vivo. We characterized the sulfation metabolism and excretion of
      calycosin using bidirectional transport studies. We confirmed that sulfate
      conjugate is breast cancer resistance protein (BCRP) substrate using the
      intestinal perfusion model and pharmacokinetics studies in Bcrp1-/- mice. Results
      showed that calycosin is rapidly and extensively metabolized to calycosin-3'
      sulfate (C-3'-S) in the intestine and liver. The overexpression of BCRP led to a
      substantial increase (approximately 14-fold, p < 0.01) of excreted C-3'-S in the
      BCRP overexpressed Madin-Darby canine kidney II (MDCK II/BCRP) cells. The
      chemical inhibition of BCRP caused reduction (about 2-fold, p < 0.01) in C-3'-S
      apical excretion. Furthermore, in intestinal perfusion studies, the deletion of
      Bcrp1 significantly decreased C-3'-S excretion in the small intestine (82.6
      90.6%, p < 0.01) and colon (97.6-98.2%, p < 0.01). In contrast, plasma level of C
      3'-S was increased to 40-fold (p < 0.01) in Bcrp1-/- mice. In conclusion,
      calycosin undergoes an extensive sulfation metabolism and BCRP is a critical
      determinant to the disposition of C-3'-S.

PMID- 28445055
TI  - Molecular Mechanism of Overhauser Dynamic Nuclear Polarization in Insulating
      Solids.
AB  - Dynamic nuclear polarization (DNP), a technique that significantly enhances NMR
      signals, is experiencing a renaissance owing to enormous methodological
      developments. In the heart of DNP is a polarization transfer mechanism that
      endows nuclei with much larger electronic spin polarization. Polarization
      transfer via the Overhauser effect (OE) is traditionally known to be operative
      only in liquids and conducting solids. Very recently, surprisingly strong OE-DNP
      in insulating solids has been reported, with a DNP efficiency that increases with
      the magnetic field strength. Here we offer an explanation for these perplexing
      observations using a combination of molecular dynamics and spin dynamics
      simulations. Our approach elucidates the underlying molecular stochastic motion,
      provides cross-relaxation rates, explains the observed sign of the NMR
      enhancement, and estimates the role of nuclear spin diffusion. The presented
      theoretical description opens the door for rational design of novel polarizing
      agents for OE-DNP in insulating solids.

PMID- 28445056
TI  - Superior Plasticity and Tabletability of Theophylline Monohydrate.
AB  - A theophylline monohydrate (THm) powder, with particle size and shape
      substantially similar to a theophylline anhydrate powder, was prepared by vapor
      mediated phase conversion. The elimination of possible contributions by particle
      size and shape to tableting properties made it possible to unambiguously identify
      the role of bonding area and bonding strength on powder tableting performance. It
      was also shown that accurate true density is essential for correct analysis and
      understanding of tableting behavior of THm. Experimental evidence revealed
      surprisingly high plasticity of THm. This is explained by its unique ladder-like
      structure, where rigid molecular dimers (rungs) weakly connect to more rigid
      water chains (rails). The low energy barrier for moving rigid dimers down the
      rigid water chains enables facile propagation of dislocations in THm crystals
      when subjected to an external stress.

PMID- 28445058
TI  - Nonideal Behavior of Glass and Crystal.
AB  - We report deviations from an ideal behavior of binary chalcogenide glass
      composition Ge20Te80 with respect to its quenching rate on mass density and
      thermal parameters, including glass transition temperature. In an ideal glass,
      the increase in quenching rate will decrease the characteristic relaxation time
      and correspondingly shift in the glass transition temperature (Tg) to higher
      temperature and result in lower density. This, however, holds only when the
      liquid structure remains the same as in equilibrium glass structure independent
      of their quenching rate. We find Ge20Te80 glass composition with higher quenching
      rate is found to possess larger density and lower Tg than the lower rate quenched
      or well annealed glass specimen. In contrast to conventional glass forming
      liquids, the anomalous behavior of Ge20Te80 glass with respect to quenching rate
      is closely related to the change in the local atomic structure with thermal
      history. Additionally, we found that crystal derived from the Ge20Te80 glass with
      different thermal history but with identical annealing conditions leads to
      different mass density, specific heat capacity, and local atomic structure. Thus,
      the observed unusual variations in the mass density and various thermal
      properties of Ge20Te80 glass and crystal are mainly determined by the resulting
      local atomic structure and concentration of defect states associated with each
      state.

PMID- 28445057
TI  - Experimental and Numerical Study of the Evaporation of Water at Low Pressures.
AB  - Although evaporation is considered to be a surface phenomenon, the rate of
      molecular transport across a liquid-vapor boundary is strongly dependent on the
      coupled fluid dynamics and heat transfer in the bulk fluids. Recent experimental
      thermocouple measurements of the temperature field near the interface of
      evaporating water into its vapor have begun to show the role of heat transfer in
      evaporation. However, the role of fluid dynamics has not been explored
      sufficiently. Here, we have developed a mathematical model to describe the
      coupling of the heat, mass, and momentum transfer in the fluids with the
      transport phenomena at the interface. The model was used to understand the
      experimentally obtained velocity field in the liquid and temperature profiles in
      the liquid and vapor, in evaporation from a concave meniscus for various vacuum
      pressures. By using the model, we have shown that an opposing buoyancy flow
      suppressed the thermocapillary flow in the liquid during evaporation at low
      pressures in our experiments. As such, in the absence of thermocapillary
      convection, the evaporation is controlled by heat transfer to the interface, and
      the predicted behavior of the system is independent of choosing between the
      existing theoretical expressions for evaporation flux. Furthermore, we
      investigated the temperature discontinuity at the interface and confirmed that
      the discontinuity strongly depends on the heat flux from the vapor side, which
      depends on the geometrical shape of the interface.

PMID- 28445059
TI  - Iron-Catalyzed Dehydrogenative sp3-sp2 Coupling via Direct Oxidative C-H
      Activation of Acetonitrile.
AB  - An iron-catalyzed dehydrogenative sp3-sp2 coupling of acetonitrile and 2
      arylimidazo[1,2-a]pyridine has been realized, which can serve as a novel approach
      toward heteroarylacetonitriles. The merit of this strategy is illustrated by the
      breadth of functional groups tolerated in the transformation and the fast access
      to pharmaceuticals (such as zolpidem) directly from the heteroarylacetonitriles.

PMID- 28445060
TI  - Asymmetric Synthesis of Carbocyclic Propellanes.
AB  - A modular synthesis of functionalized carbocyclic propellanes was developed.
      Formation of the first of two quaternary bridgehead centers has been achieved by
      desymmetrization of prostereogenic ketones by either Hajos-Parrish-Eder-Sauer
      Wiechert-type processes or Werner's catalytic asymmetric Wittig reaction. The
      obtained bicyclic enones were subjected to conjugate additions upon which the
      remaining ring was formed by olefin metathesis. All bridges are amenable to
      further derivatization, which renders those compounds useful as central units in
      fragment-based drug discovery or as ligand scaffolds.

PMID- 28445061
TI  - Synergistic Visible-Light Photoredox/Nickel-Catalyzed Synthesis of Aliphatic
      Ketones via N-C Cleavage of Imides.
AB  - An electrophilic, imide-based, visible-light-promoted photoredox/Ni-catalyzed
      cross-coupling reaction for the synthesis of aliphatic ketones has been
      developed. This protocol proceeds through N-C(O) bond activation, made possible
      through the lower activation energy for metal insertion into this bond due to
      delocalization of the lone pair of electrons on the nitrogen by electron
      withdrawing groups. The operationally simple and mild cross-coupling reaction is
      performed at ambient temperature and exhibits tolerance for a variety of
      functional groups.

PMID- 28445062
TI  - Regioselective Functionalization of Enamides at the alpha-Carbon via
      Unsymmetrical 2-Amidoallyl Cations.
AB  - A new method to functionalize enamides via an intermediacy of unsymmetrical 2
      amidoallyl cations is reported. Generated under mild Bronsted acid catalysis,
      these reactive species were found to undergo addition with various nucleophiles
      at the less substituted alpha-carbon to produce highly substituted enamides in
      high yields with complete control of regioselectivity.

PMID- 28445063
TI  - Role of Configuration at C6 in Catalytic Activity of l-Proline-Derived
      Bifunctional Organocatalysts.
AB  - l-Proline-derived chiral bifunctional (thio)urea organocatalysts epi-PTU and epi
      PU were newly synthesized, and their catalytic performances were compared with
      their C6 epimeric catalysts PTU and PU in various Michael reactions of
      nitrostyrene in terms of reactivities and stereoselectivities. The experimental
      results indicate that a proper relative stereochemistry at C2 and C6 in l-proline
      derived bifunctional organocatalysts is important for successful catalysis and
      that catalysts (PTU and PU) with the 2S,6R configuration are much more efficient.

PMID- 28445064
TI  - Enantioselective Michael Addition of Photogenerated o-Quinodimethanes to Enones
      Catalyzed by Chiral Amino Acid Esters.
AB  - The first example of a photoexcitated amine-catalyzed process for asymmetric
      Michael addition of o-quinodimethanes to enones is described. In the presence of
      simple chiral amino acid esters, a variety of Michael adducts were generally
      obtained in good yields and excellent stereoselectivities. This strategy can be
      successfully applied to 3-substituted-2-cyclohexenones and provides an asymmetric
      access to all-carbon quaternary centers. Furthermore, the high stereocontrol was
      explained by means of density-functional theory (DFT) calculations.

PMID- 28445065
TI  - Neomacrophorin X, a [4.4.3]Propellane-Type Meroterpenoid from Trichoderma sp.
      1212-03.
AB  - Neomacrophorin X (1) was isolated from Trichoderma sp. 1212-03. Heteronuclear
      multiple bond correlation (HMBC) spectral analysis indicated a unique
      [4.4.3]propellane framework, which was verified by the 1H and 13C chemical shift
      calculations based on density functional theory (DFT) and subsequent comparison
      with experimental data obtained in CDCl3. The DFT-based electronic circular
      dichroism (ECD) calculations were effective in not only determining the absolute
      configuration but also confirming the relative structure. The predominant
      conformation of 1 was found to be solvent-dependent, with different conformations
      presenting different NMR and ECD profiles. Introduction of J-based analysis with
      a J-resolved HMBC aided in this investigation. This conformational alternation
      was reproduced by considering the solvation with the SM5.4 model in the
      calculation, although it was not sufficiently quantitative. Although the
      calculations without solvent effects suggested a conformer that satisfies the
      spectral profiles in CDCl3, postcalculations with the SM5.4 solvation protocol
      stabilized the second major conformer, which reproduces the NMR and ECD profiles
      in polar solvents. Neomacrophorin X (1) is assumed to be biosynthesized by a
      coupling between the reduced form of anthraquinone and a neomacrophorin
      derivative. This hypothesis was supported experimentally by the isolation of
      pachybasin and chrysophanol, as well as acyclic premacrophorin (2), from the same
      fungus. Some biological properties of 1 are described.

PMID- 28445066
TI  - Deoxygenation of Ethers To Form Carbon-Carbon Bonds via Nickel Catalysis.
AB  - In this article a successful protocol was developed to construct carbon-carbon
      bonds by the extrusion of the O atom of ethers via nickel catalysis in the
      presence of reductants. This methodology is featured as a highly economic route
      to construct sp3-sp3 C-C bonds through dual C-O activation of ethers with good
      functional group tolerance.

PMID- 28445067
TI  - Photoelectrochemical Degradation of Organic Compounds Coupled with Molecular
      Hydrogen Generation Using Electrochromic TiO2 Nanotube Arrays.
AB  - Vertically aligned TiO2 nanotube arrays (TNTs) were prepared by electrochemical
      anodization, and then cathodically polarized with dark blue coloration for the
      dual-functional photoelectrochemical water treatment of organic substrates
      degradation and accompanying H2 generation. The resulting Blue-TNTs (inner
      diameter: ~40 nm; length: ~9 MUm) showed negligible shift in X-ray diffraction
      pattern compared with the intact TNTs, but the X-ray photoelectron spectra
      indicated a partial reduction of Ti4+ to Ti3+ on the surface. The electrochemical
      analyses of Blue-TNTs revealed a marked enhancement in donor density and
      electrical conductivity by orders of magnitude. Degradations of test organic
      substrates on Blue-TNTs were compared with the intact TNTs in electrochemical
      (EC), photocatalytic (PC), and photoelectrochemical (PEC) conditions (potential
      bias: 1.64 VNHE; lambda > 320 nm). The degradation of 4-chlorophenol was greatly
      enhanced on Blue-TNTs particularly in PEC condition, whereas the PC activities of
      the Blue- and intact TNTs were similar. The potential bias of 1.64 VNHE did not
      induce any noticeable activity in EC condition. Similar trends were observed for
      the degradation of humic acid and fulvic acid, where main working oxidants were
      found to be the surface hydroxyl radical as confirmed by hydroxyl radical probe
      and scavenger tests. H2 generation coupled with the organic degradation was
      observed only in PEC condition, where the H2 generation rate with Blue-TNTs was
      more than doubled from that of intact TNTs. Such superior PEC activity was not
      observed when a common TiO2 nanoparticle film was used as a photoanode. The
      enhanced electric conductivity of Blue-TNTs coupled with a proper band bending in
      PEC configuration seemed to induce a highly synergic enhancement.

PMID- 28445068
TI  - Experimental Demonstration of >230 degrees  Phase Modulation in Gate-Tunable
      Graphene-Gold Reconfigurable Mid-Infrared Metasurfaces.
AB  - Metasurfaces offer significant potential to control far-field light propagation
      through the engineering of the amplitude, polarization, and phase at an
      interface. We report here the phase modulation of an electronically
      reconfigurable metasurface and demonstrate its utility for mid-infrared beam
      steering. Using a gate-tunable graphene-gold resonator geometry, we demonstrate
      highly tunable reflected phase at multiple wavelengths and show up to 237 degrees
      phase modulation range at an operating wavelength of 8.50 MUm. We observe a
      smooth monotonic modulation of phase with applied voltage from 0 degrees  to 206
      degrees  at a wavelength of 8.70 MUm. Based on these experimental data, we
      demonstrate with antenna array calculations an average beam steering efficiency
      of 23% for reflected light for angles up to 30 degrees  for this range of phases,
      confirming the suitability of this geometry for reconfigurable mid-infrared beam
      steering devices. By incorporating all nonidealities of the device into the
      antenna array calculations including absorption losses which could be mitigated,
      1% absolute efficiency is achievable up to 30 degrees .

PMID- 28445070
TI  - Enantioselective [4 + 2] Cycloaddition of o-Quinone Methides and Vinyl Sulfides:
      Indirect Access to Generally Substituted Chiral Chromanes.
AB  - A catalytic asymmetric [4 + 2] cycloaddition of ortho-quinone methides (o-QMs) is
      described. With the readily available vinyl sulfides as the key 2pi partner and a
      properly chosen chiral phosphoric acid catalyst, the reaction proceeded under
      mild conditions to form the corresponding adduct with high enantio- and
      diastereoselectivity. Owning to the easy removal and conversion of the sulfenyl
      group in the product, the present process provides indirect access to generally
      substituted chromanes previously lacking easy access. Mechanistically, the
      reaction is also a new demonstration of the rarely achieved sole activation of o
      QM for asymmetric control.

PMID- 28445069
TI  - Targeted Dereplication of Microbial Natural Products by High-Resolution MS and
      Predicted LC Retention Time.
AB  - A new strategy for the identification of known compounds in Streptomyces extracts
      that can be applied in the discovery of natural products is presented. The
      strategy incorporates screening a database of 5555 natural products including
      5098 structures from Streptomyces sp., using a high-throughput LCMS data
      processing algorithm that utilizes HRMS data and predicted LC retention times
      (tR) as filters for rapid identification of known compounds in the natural
      product extract. The database, named StrepDB, contains for each compound the
      structure, molecular formula, molecular mass, and predicted LC retention time.
      All identified compounds are annotated and color coded for easier visualization.
      It is an indirect approach to quickly assess masses (which are not annotated)
      that may potentially lead to the discovery of new or novel structures. In
      addition, a spectral database named MbcDB was generated using the ACD/Spectrus DB
      Platform. MbcDB contains 665 natural products, each with structure, experimental
      HRESIMS, MS/MS, UV, and NMR spectra. StrepDB was used to screen a mutant
      Streptomyces albus extract, which led to the identification and isolation of two
      new compounds, legonmaleimides A and B, the structures of which were elucidated
      with the aid of MbcDB and spectroscopic techniques. The structures were confirmed
      by computer-assisted structure elucidation (CASE) methods using ACD/Structure
      Elucidator Suite. The developed methodology suggests a pipeline approach to the
      dereplication of extracts and discovery of novel natural products.

PMID- 28445071
TI  - Polymorphic Assembly from Beveled Gold Triangular Nanoprisms.
AB  - The shape anisotropy of nanoparticle building blocks is of critical importance in
      determining their packing symmetry and assembly directionality. While there has
      been extensive research on the effect of their overall geometric shapes, the
      importance of nanometer morphology details is not well-recognized or understood.
      Here we draw on shape-anisotropic gold triangular nanoprism building blocks
      synthesized based on a method we recently developed; besides the "large-scale"
      triangular prism shape (79.8 nm in side length and 22.0 nm in thickness), the
      prisms are beveled with their sides convexly enclosed by two flat {100} facets.
      We engineer the balance between electrostatic repulsion and entropically driven
      depletion attraction in the system to generate self-assemblies without or with
      the effect of the nanoscale beveling detail. A conventional, planar honeycomb (p
      honeycomb) lattice forms with the triangular basal planes packed on the same
      plane at low depletion attraction, whereas an unexpected interlocking honeycomb
      (i-honeycomb) lattice and its "supracrystal" forms are assembled with additional
      close-paralleling of side facets at high depletion attraction. The i-honeycomb
      lattice renders all the metallic surfaces in close proximity and leads to a
      surface-enhanced Raman scattering signal nearly 5-fold higher than that in the p
      honeycomb lattice and high sensitivity for detecting the model molecule Rhodamine
      6G at a concentration as low as 10-8 M. Our study can guide future work in both
      nanoparticle synthesis and self-assembly; nanoscale geometrical features in
      anisotropic nanoparticles can be used as an important handle to control
      directional interactions for nonconventional ordered assemblies and to enrich
      diversity in self-assembly structure and function.

PMID- 28445072
TI  - An Approach to the Core of Lactonamycin.
AB  - A cascade reaction has been developed for the synthesis of lactonamycin. In this
      paper, we demonstrate that a transition-metal-free thermal ene-diyne cyclization
      can be used for the construction of the entire core of the antibiotic
      lactonamycin and anticancer agent lactonamycin Z.

PMID- 28445074
TI  - Unravelling chloroma: review of imaging findings.
AB  - Chloroma refers to the extramedullary proliferation of immature myeloid
      precursors occurring in a gamut of myeloproliferative and myelodysplastic
      conditions; acute myeloid leukaemia being the commonest. With non-specific
      clinical and imaging manifestations, it runs a high risk of misdiagnosis which
      may significantly affect the outcome of an otherwise treatable lesion. Also with
      these lesions heralding impending blast crises, awareness of the imaging findings
      becomes imperative. Imaging not only helps raise the suspicion but also guides
      further confirmation by demonstration of specific immunohistochemistry markers,
      ensuring timely institution of chemotherapy. In general, solid enhancing lesions
      in any haematological disorder could be chloromas, especially if multifocal with
      mass effect.

PMID- 28445073
TI  - Plasminogen Activator Inhibitor-1 Is Critical in Alcohol-Enhanced Acute Lung
      Injury in Mice.
AB  - Chronic alcohol exposure is a clinically important risk factor for the
      development of acute respiratory distress syndrome, the most severe form of acute
      lung injury (ALI). However, the mechanisms by which alcohol sensitizes the lung
      to development of this disease are poorly understood. We determined the role of
      the antifibrinolytic protein plasminogen activator inhibitor-1 (PAI-1) in alcohol
      enhancement of experimental endotoxin-induced ALI. Wild-type, PAI-1-/-, and
      integrin beta3-/- mice were fed ethanol-containing Lieber-DeCarli liquid or a
      control diet for 6 weeks, followed by systemic LPS challenge. LPS administration
      triggered coagulation cascade activation as evidenced by increased plasma
      thrombin-antithrombin levels and pulmonary fibrin deposition. Ethanol-exposed
      animals showed enhanced PAI-1 expression and pulmonary fibrin deposition with
      coincident exaggeration of pulmonary inflammatory edematous injury. PAI-1
      deficiency markedly reduced pulmonary fibrin deposition and greatly reduced
      inflammation and injury without impacting upstream coagulation. Interestingly,
      pulmonary platelet accumulation was effectively abolished by PAI-1 deficiency in
      ethanol/LPS-challenged mice. Moreover, mice lacking integrin alphaIIBbeta3, the
      primary platelet receptor for fibrinogen, displayed a dramatic reduction in early
      inflammatory changes after ethanol/LPS challenge. These results indicate that the
      mechanism whereby alcohol exaggerates LPS-induced lung injury requires PAI-1
      mediated pulmonary fibrin accumulation, and suggest a novel mechanism whereby
      alcohol contributes to inflammatory ALI by enhancing fibrinogen-platelet
      engagement.

PMID- 28445076
TI  - Image-Based Phenotypic Screening with Human Primary T Cells Using One-Dimensional
      Imaging Cytometry with Self-Tuning Statistical-Gating Algorithms.
AB  - The parallel microfluidic cytometer (PMC) is an imaging flow cytometer that
      operates on statistical analysis of low-pixel-count, one-dimensional (1D) line
      scans. It is highly efficient in data collection and operates on suspension
      cells. In this article, we present a supervised automated pipeline for the PMC
      that minimizes operator intervention by incorporating multivariate logistic
      regression for data scoring. We test the self-tuning statistical algorithms in a
      human primary T-cell activation assay in flow using nuclear factor of activated T
      cells (NFAT) translocation as a readout and readily achieve an average Z' of 0.55
      and strictly standardized mean difference of 13 with standard phorbol myristate
      acetate/ionomycin induction. To implement the tests, we routinely load 4 uL
      samples and can readout 3000 to 9000 independent conditions from 15 mL of primary
      human blood (buffy coat fraction). We conclude that the new technology will
      support primary-cell protein-localization assays and "on-the-fly" data scoring at
      a sample throughput of more than 100,000 wells per day and that it is, in
      principle, consistent with a primary pharmaceutical screen.

PMID- 28445075
TI  - Dried Plum Ingestion Increases the Osteoblastogenic Capacity of Human Serum.
AB  - In cell culture studies, dried plum (Prunus domestica L.) polyphenols increased
      osteoblast alkaline phosphatase (ALP) activity, mineralized nodule formation, and
      the expression of the bone marker genes runt-related transcription factor 2
      (RUNX2) and osterix. The purpose of this study was to determine whether human
      serum collected 1 and 2 h after dried plum ingestion influenced osteoblast cell
      activity and gene expression. Five healthy women ingested 100 g of dried plum,
      and serum samples were collected at baseline (before dried plum ingestion) and 1
      and 2 h postingestion of dried plum. MC3T3-E1 osteoblast cells were treated (2%
      of medium) with these serum samples for 3 or 9 days. Intracellular and
      extracellular ALP activities were significantly increased after 3 or 9 days of
      treatment with serum both postingestion time points, with no effect seen in
      baseline samples. Also, serum obtained 1 and 2 h postingestion significantly
      increased the mRNA expression of bone markers RUNX2 and connexin43 (CX43) after
      both 3 and 9 days of incubation periods. Finally, serum obtained 1 and 2 h
      postingestion increased the mRNA expression of beta-catenin after 9 days of
      incubation. We conclude that osteoblast activity and function are increased by
      dried plum ingestion, which may, in part, explain its beneficial effects on bone
      health.

PMID- 28445077
TI  - Effect of Epiretinal Membranes on Antivascular Endothelial Growth Factor
      Treatment for Neovascular Age-Related Macular Degeneration.
AB  - PURPOSE: To evaluate the effect of epiretinal membranes (ERMs), detected with
      spectral-domain optical coherence tomography (SD-OCT), on the outcome of
      antivascular endothelial growth factor (VEGF) treatment for neovascular age
      related macular degeneration (nAMD). METHODS: A total of 434 eyes with treatment
      naive nAMD were retrospectively included and analyzed. All patients were
      administered an initial series of 3 monthly loading injections of ranibizumab or
      aflibercept, followed by further injections as required. The visual and
      anatomical outcomes were compared between the eyes with ERMs and those without.
      Features of ERMs at baseline assessed with SD-OCT were evaluated and correlated
      with visual outcomes. RESULTS: Sixty-eight eyes (15.7%) with nAMD presented ERMs
      at baseline. The mean best-corrected visual acuity (BCVA) of these eyes,
      expressed as the logarithm of the minimum angle of resolution, improved from 0.75
      +/- 0.48 (Snellen equivalent: 20/112) to 0.59 +/- 0.44 (20/77) after 12 months of
      treatment (P = 0.021). Central foveal thickness also decreased from 381 +/- 191
      MUm to 294 +/- 167 MUm (P < 0.001). Compared to the eyes without ERMs (366 eyes),
      the eyes with ERMs had a significantly thicker central fovea after treatment (P =
      0.020). However, the intergroup differences in BCVA improvement were not
      significant. No significant association was found between visual outcome after
      treatment and ERM features on OCT at baseline. CONCLUSIONS: In eyes with nAMD,
      ERMs were infrequent. Central foveal thickness was significantly greater after
      anti-VEGF treatment in eyes with nAMD and ERMs. However, the presence of ERMs in
      eyes with nAMD did not affect visual outcome.

PMID- 28445078
TI  - Effects of high-intensity interval training on canoeing performance.
AB  - The purpose of this study was to compare the effects of high-intensity interval
      training (HIIT) and moderate-intensity continuous training (MICT) utilizing a
      canoeing ergometer on endurance determinants, as well as aerobic and anaerobic
      performances among flat-water canoeists. Fourteen well-trained male flat-water
      canoeists were divided into an HIIT group or an MICT group. All subjects
      performed a continuous graded exercise test (GXT) and three fixed-distance (200,
      500, and 1000 m) performance tests on a canoeing ergometer to determine canoeing
      economy, peak oxygen uptake (VO2peak), and power at VO2peak, and to calculate the
      critical velocity (CV) and anaerobic work capacity before and after the training
      programmes. The training programme involved training on a canoeing ergometer
      three times per week for four weeks. HIIT consisted of seven 2 min canoeing bouts
      at an intensity of 90% VO2peak separated by 1 min of rest. The MICT group was
      trained at an intensity of 65% VO2peak continuously for 20 min. After four weeks
      of training, performance in the 200-m distance test and the power at VO2peak
      significantly improved in the HIIT group; performance in the 500 m and 1000 m
      distances and CV significantly improved in the MICT group. However, all variables
      were not significantly different between groups. It is concluded that HIIT for
      four weeks is an effective training strategy for improvement of short-distance
      canoeing performance. In contrast, MICT improves middle-distance canoeing
      performances and aerobic capacity.

PMID- 28445079
TI  - Multiple Antimicrobial Resistance and Novel Point Mutation in Fluoroquinolone
      Resistant Escherichia coli Isolates from Mangalore, India.
AB  - Fluoroquinolone resistance in bacteria is usually associated with mutations in
      the topoisomerase regions. We report a novel point mutation in fluoroquinolone
      resistant Escherichia coli strains. E. coli isolated from the environment in and
      around Mangalore, India, were examined for their antimicrobial resistance profile
      to 12 antibiotics and for the antibiotic resistance genes by polymerase chain
      reaction. Of the 67 E. coli isolated, 24 (35.8%) were sensitive to all
      antibiotics and 43 (64.2%) showed resistance to at least one of the 12
      antibiotics used in the study. One isolate (EC10) was resistant to nine of the 12
      antibiotics used. Resistance to nalidixic acid was the most common (34.32%),
      followed by nitrofurantoin (26.86%), tetracycline (22.38%), ampicillin (20.89%),
      cotrimoxazole (13.43%), ciprofloxacin (11.94%), gentamicin (10.44%),
      piperacillin/tazobactam (7.46%), chloramphenicol (7.46%), and cefotaxime (4.47%).
      Least resistance was observed for meropenem (1.49%) and none of the isolates
      showed resistance to imipenem. All the isolates harbored resistance genes
      corresponding to their antimicrobial resistance. Few quinolone-resistant isolates
      carried single point mutation (ser83Leu) and some had double point mutation
      (Ser83Leu and Asp87Asn) in gyrA. A third novel point mutation was also observed
      at position 50 with the change in the amino acid from tyrosine to cysteine
      (Tyr50Cys) in gyrA region. The study throws light on a novel point mutation in
      fluoroquinolone-resistant isolates. While the study helps to understand the risk
      and occurrence of antibiotic resistance among gram-negative bacteria from the
      environment, the alarming rate of antibiotic-resistant bacteria is a cause of
      concern in addressing infections.

PMID- 28445080
TI  - Bridging the Data-Sharing Divide - Seeing the Devil in the Details, Not the Other
      Camp.

PMID- 28445081
TI  - ?

PMID- 28445082
TI  - The impact of beta-amyloid positron emission tomography on the diagnostic and
      treatment decisions of dementia experts.
AB  - AIM: Amyloid positron emission tomography (aPET) measurement of Alzheimer's
      disease (AD) pathology could improve the accurate diagnosis of cognitive
      disorders. Appropriate use criteria recommend that only dementia experts order
      aPET. MATERIALS & METHODS: We surveyed 145 dementia experts about their current
      approaches to evaluation and treatment and the likely influence of aPET. RESULTS:
      Experts expected aPET to alter diagnostic procedures and patient management and
      also increase diagnostic certainty. They anticipated confirming AD or altering
      pharmacological treatment following positive results more than excluding AD
      following negative results. Experts familiar with aPET reported changes that were
      more consistent with appropriate use criteria and published evidence.
      CONCLUSIONS: Knowledge about aPET strongly influenced effects on diagnostic
      certainty and changed clinical practice. Dementia experts may need additional
      training to achieve optimal benefit from aPET.

PMID- 28445083
TI  - Fatigue and physical functioning in children with multiple sclerosis and acute
      disseminated encephalomyelitis.
AB  - BACKGROUND AND OBJECTIVE: Fatigue and physical impairments are a major concern in
      children with multiple sclerosis (MS) and after acute disseminated
      encephalomyelitis (post-ADEM). We here aimed to evaluate the interaction between
      fatigue, exercise capacity, motor performance, neurological status, and quality
      of life (HRQoL). METHODS: In this cross-sectional study, data of 38 children (MS
      n = 22, post-ADEM n = 16), aged 4-17 years attending our national pediatric MS
      center, were studied. Fatigue was measured with the Pediatric Quality of Life
      Multidimensional Fatigue Scale, exercise capacity with the Bruce Protocol, motor
      performance with the Movement Assessment Battery for Children second edition,
      HRQoL with the Pediatric Quality of Life Questionnaire, and extent of disability
      with the Expanded Disability Status Scale (EDSS). RESULTS: Children with MS and
      post-ADEM experienced more fatigue ( p < 0.001), reduced exercise capacity ( p <
      0.001), and impaired motor performance ( p < 0.001), despite low scores on the
      EDSS. Fatigue, but not the other parameters, was significantly correlated with
      HRQoL. Fatigue was not correlated with exercise capacity. CONCLUSION: We confirm
      the major impact of fatigue on quality of life in children with MS and post-ADEM.
      Fatigue was not explained by reduced exercise capacity or impaired motor
      performance. An important finding for clinical practice is that the low EDSS
      score did not reflect the poor physical functioning.

PMID- 28445084
TI  - Brain atrophy 15 years after CIS: Baseline and follow-up clinico-radiological
      correlations.
AB  - BACKGROUND: Brain atrophy in multiple sclerosis (MS) patients is present since
      the very early stages of the disease and it has been related to long-term
      disability. OBJECTIVE: To estimate brain volume (BV) at 15 years after a
      clinically isolated syndrome (CIS) and to evaluate its relationship with disease
      outcomes. METHODS: From a prospective cohort including patients presenting with a
      CIS, 54 patients with a brain magnetic resonance imaging (MRI) performed 15 years
      after CIS were included. Brain parenchymal fraction (BPF), grey matter fraction
      (GMF) and white matter fraction (WMF) at 15-year follow-up were obtained.
      Regression analyses were conducted to predict BV loss and reaching an Expanded
      Disability Status Scale (EDSS) of 3.0 in that 15-year period. RESULTS: In
      multivariable analyses, lower values of BPF and WMF were significantly associated
      with being male, presenting 3-4 Barkhof criteria at baseline, presenting a second
      relapse, and with a decision to start treatment. In the multivariable logistic
      regression analysis, only lower GMF was associated with a greater risk of
      reaching EDSS 3.0 (odds ratio (OR) = 0.24, p = 0.028). CONCLUSION: Lower BPF and
      WMF 15 years after CIS are associated with previous markers of inflammatory
      disease. Lower GMF 15 years after a CIS is associated with an increased risk of
      reaching an EDSS of 3.0.

PMID- 28445085
TI  - Regenerative Surgery in the Treatment of Cosmetic Defect Following Nuss
      Procedure.
AB  - BACKGROUND: In the past decade, the minimally invasive repair of pectus excavatum
      (MIRPE) has become the treatment of choice for severe pectus excavatum (PE),
      proving acceptable to excellent cosmetic results. Recently, autologous fat
      grafting (FG) has been identified in aesthetic and reconstructive surgery to
      ideally handle volume and contour defects. We report our experience about FG in
      the treatment of residual minor defects after MIRPE and a proposal for a new
      indication of this largely adopted technique. MATERIALS AND METHODS: From April
      2012 to April 2015, 127 patients underwent bar removal. At outpatient check, a
      questionnaire was adopted to investigate aesthetic outcome prior and after
      surgery (3 months postoperation); scoring options varied from 4 to 0 [4,
      excellent; 3, very good; 2, good; 1, acceptable; and 0, unacceptable]. In
      patients scoring less than "good," we proposed FG at the same operating session
      of bar removal. The donor areas were the abdomen, trochanteric region, and inner
      thigh. The tissue was gently collected through a thin cannula, filtrated, and
      then promptly injected into the defect. RESULTS: Eleven patients (8.8%) have been
      selected for FG. No complications have been detected during the follow-up period
      (range 1-36 months). In three cases, we performed further FG procedure to achieve
      an optimal result. Questionnaire reported an increased mean score from 1.8 to
      2.7. CONCLUSION: In our early experience, FG has provided satisfactory cosmetic
      results. With the present report we advocate FG as a minimally invasive "tool" to
      achieve better defect correction after MIRPE. These preliminary results suggest
      that FG could be a worthwhile resource in treating chest wall malformations.

PMID- 28445086
TI  - Long Noncoding RNA Highly Upregulated in Liver Cancer Activates p53-p21 Pathway
      and Promotes Nasopharyngeal Carcinoma Cell Growth.
AB  - Dysfunction of lncRNA has been found in the nasopharyngeal carcinoma (NPC);
      however, the effect of lncRNA expression on NPC tumorigenesis as well as the
      molecular mechanism of lncRNA in the pathogenesis of NPC remain largely unknown.
      In this study, we showed that highly upregulated in liver cancer (HULC), the
      first identified lncRNA in hepatocellular carcinoma, is highly expressed in NPC
      patients and correlated with a poor prognosis of cancer patients. Overexpressed
      HULC promotes NPC cell growth. Downregulation of HULC activated p53 and induced
      the increased expression of p21, which finally caused cell cycle arrest and cell
      apoptosis. These results suggested that HULC acts as an oncogenic lncRNA in NPC
      and a potential therapeutic target in NPC treatment.

PMID- 28445087
TI  - Cardioprotection by Mild Hypothermia Is Abolished in Aged Mice.
AB  - Mild hypothermia (MH) renders the hearts resistant to ischemia/reperfusion (IR)
      injury in animal experiments. Unexpectedly, this effect was not observed in
      recent clinical trials. The aged hearts in mice have been demonstrated to be more
      susceptible to IR injury. This study aimed to examine whether the
      cardioprotection of MH was abolished in aged mice. Young (Y, 3 months old) and
      aged (A, 20 months old) male C57BL/6 mice were randomized into six groups. Sham
      (Y-SHAM and A-SHAM) and control (Y-CON+IR and A-CON+IR) animals maintained core
      body temperature at 37 degrees C +/- 0.5 degrees C; MH groups (Y-MH+IR and A
      MH+IR) received surface cooling and kept core body temperature at 32-35 degrees C
      before ischemia until reperfusion. The IR mice underwent 40 minutes of ischemia
      followed by 24 hours of reperfusion. Finally, the cardiac function and infarct
      size (IS) were evaluated. The A-CON+IR group exhibited more severe cardiac
      dysfunction compared with the Y-CON+IR group showing as decreased ejection
      fraction (EF) (34.8% +/- 8.5% vs. 44.2% +/- 5.9%) and fraction shortening (FS)
      (15.2% +/- 4.1% vs. 21.8% +/- 3.7%). MH restored EF to 55.3% +/- 6.1% and FS to
      28.5% +/- 3.6% in the Y-MH+IR group but not in the A-MH+IR group. Similarly, IS
      was significantly increased in the A-CON+IR group compared with the Y-CON+IR
      group (54.5% +/- 10.6% vs. 42.0% +/- 6.4%). MH lessened the IS to 21.3% +/- 7.6%
      in the Y-MH+IR group but not in the A-MH+IR group. Thus, the cardioprotection
      rendered by MH is abolished in aged mice.

PMID- 28445089
TI  - Genetic and Morphological Differentiation of the Semiterrestrial Crab Armases
      angustipes (Brachyura: Sesarmidae) along the Brazilian Coast.
AB  - The genetic and morphometric population structures of the semiterrestrial crab
      Armases angustipes from along the Brazilian coast were examined. The influence of
      the Central South Equatorial Current on larval dispersal of A. angustipes also
      was evaluated. Six populations were sampled from estuarine areas in Sao Luis do
      Maranhao, Maranhao; Natal, Rio Grande do Norte; Maceio, Alagoas; Ilheus, Bahia;
      Aracruz, Espirito Santo; and Guaratuba, Parana. Patterns of genetic
      differentiation were assessed using DNA sequence data corresponding to parts of
      the mitochondrial cytochrome c oxidase subunit 1. Geometric morphometric
      techniques were used to evaluate morphological variation in shape and size of the
      carapace and right cheliped propodus. Our results revealed low genetic
      variability and lack of phylogeographic structure; geometric morphometrics showed
      statistically significant morphological differentiation and geographic
      structuring. Our data indicate the absence of possible barriers to gene flow for
      this mobile species, and no clear correlation of morphological or genetic
      variation with ocean currents and/or geographic distance. Our results also
      suggest that historical geological and climatological events and/or possible
      bottleneck effects influenced the current low genetic variability among the
      populations of A. angustipes.

PMID- 28445088
TI  - Predicting the Need for Third-Line Antiretroviral Therapy by Identifying Patients
      at High Risk for Failing Second-Line Antiretroviral Therapy in South Africa.
AB  - Although third-line antiretroviral therapy (ART) is available in South Africa's
      public sector, its cost is substantially higher than first and second line.
      Identifying risk factors for failure on second-line treatment remains crucial to
      reduce the need for third-line drugs. We conducted a case-control study including
      194 adult patients (>=18 years; 70 cases and 124 controls) who initiated second
      line ART in Johannesburg, South Africa. Unconditional logistic regression was
      used to assess predictors of virologic failure (defined as 2 consecutive viral
      load measures >=1000 copies/mL, >=3 months after switching to second line).
      Variables included a social instability index, ART adherence, self-reported as
      well as diagnosed adverse drug reactions (ADRs), HIV disclosure, depression, and
      factors affecting access to HIV clinics. Overall 60.0% of cases and 54.0% of
      controls were female. Mean ages of cases and controls were 41.8 +/- 9.6 and 43.3
      +/- 8.0, respectively. Virologic failure was predicted by ART adherence <90%
      [odds ratio (OR) 4.7; 95% confidence interval (95% CI): 2.1-10.5], younger age
      (<40 years of age; OR 0.6; 95% CI: 0.3-1.1), high social instability (OR 3.8; 95%
      CI: 1.30-11.5), self-reported ADR (OR 1.9; 95% CI: 1.0-3.5), disclosure to
      friends/colleagues rather than partner/relatives (OR 3.4; 95% CI: 1.3-9.1), and
      medium/high depression compared to low/no depression (OR 4.4; 95% CI: 1.5-13.4).
      Our results suggest complex socioeconomic factors contributing to risk of
      virologic failure, possibly by impacting ART adherence, among patients on second
      line therapy in South Africa. Identifying patients with possible indicators of
      nonadherence could facilitate targeted interventions to reduce the risk of second
      line treatment failure and mitigate the demand for third-line regimens.

PMID- 28445090
TI  - Embracing Tradition and Change.

PMID- 28445091
TI  - Comparative Molecular and Morphological Variation Analysis of Siderastrea
      (Anthozoa, Scleractinia) Reveals the Presence of Siderastrea stellata in the Gulf
      of Mexico.
AB  - The genus Siderastrea exhibits high levels of morphological variability. Some of
      its species share similar morphological characteristics with congeners, making
      their identification difficult. Siderastrea stellata has been reported as an
      intermediary of S. siderea and S. radians in the Brazilian reef ecosystem. In an
      earlier study conducted in Mexico, we detected Siderastrea colonies with
      morphological features that were not consistent with some siderastreid species
      previously reported in the Gulf of Mexico. Thus, we performed a combined
      morphological and molecular analysis to identify Siderastrea species boundaries
      from the Gulf of Mexico. Some colonies presented high morphologic variability,
      with characteristics that corresponded to Siderastrea stellata. Molecular
      analysis, using the nuclear ITS and ITS2 region, corroborated the morphological
      results, revealing low genetic variability between S. radians and S. stellata.
      Since the ITS sequences did not distinguish between Siderastrea species, we used
      the ITS2 region to differentiate S. stellata from S. radians. This is the first
      report of Siderastrea stellata and its variability in the Gulf of Mexico that is
      supported by morphological and molecular analyses.

PMID- 28445092
TI  - Frontmatter.

PMID- 28445093
TI  - Dynamics of Cytokine-like Activity in the Hyperplasic Ovary of Ex-fissiparous
      Planarians.
AB  - The origin of infertility in the hyperplasic ovary of ex-fissiparous planarians
      remains poorly understood. In a previous study we demonstrated that a complex
      process of early autophagy, followed by apoptotic processes, occurs in the
      hyperplasic ovary of the freshwater planarian Dugesia arabica. The present study
      aimed to investigate whether the mRNA expression levels of selected mRNA-like
      genes are altered in the hyperplasic ovary of the ex-fissiparous freshwater
      planarian D. arabica compared to the normal ovary. Using human cytokine-specific
      primers including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis
      factor-alpha (TNF-alpha), we have successfully amplified by real-time polymerase
      chain reaction some transcripts that could be similar to those amplified in
      human. The transcript levels of the human-like transcript (IL-1-like and TNF
      alpha-like) were significantly higher, 4.89- and 3.41-fold, respectively, in the
      hyperplasic ovary compared to the normal ovary (P < 0.05). However, although IL-6
      like levels were higher in the hyperplasic ovary than the normal ovary (2.57
      fold), this difference was not significant (P > 0.05). Immunohistochemical
      labeling supported the quantitative real-time PCR, showing that, like their
      respective mRNA expression levels, IL-1, IL-6, and TNF-alpha-like proteins are
      more highly expressed in the hyperplasic ovary than in the normal ovary.

PMID- 28445094
TI  - Proteinases during Early Development of the Pacific Whiteleg Shrimp Penaeus
      vannamei.
AB  - During shrimp larval development, changes occur in molecular components. Enzyme
      activity and mRNA expression of proteinases were assayed in Penaeus vannamei
      during larval development, which consists of 5 nauplius stages, 3 protozoeal
      stages, 3 mysis stages, and 12 postlarval stages. Trypsin activity reached a
      maximum at the beginning of postlarval stages 1 and 2, and significantly
      decreased in subsequent postlarval stages. Chymotrypsin activity increased at the
      third protozoeal stage, then significantly decreased in subsequent stages.
      Identification of proteinase by mass spectrometry and inhibitors allowed us to
      track their appearance in zymograms and to distinguish between isoenzymes.
      Chymotrypsin BI and BII had a distinguishing pattern of appearance during larval
      development, which could compensate for the reduction in trypsin activity. The
      mRNA content of isotrypsin 21, chymotrypsin 1, and zinc proteinase was
      differentially expressed in larvae. Zinc proteinase and chymotrypsin 1 mRNA were
      expressed at a basal content at the beginning of the protozoeal stages, increased
      by the end of the mysis stages and onward, while isotrypsin 21 mRNA had a peak at
      mysis stage 3. Transcript changes reflect transcriptional regulation of the
      proteinases tested. Proteinase mRNA in tissues, other than the digestive gland,
      suggests potentially different roles besides digestion during ontogeny.

PMID- 28445095
TI  - Physical versus Biological Control in Bivalve Calcite Prisms: Comparison of
      Euheterodonts and Pteriomorphs.
AB  - Multiple groups of bivalve molluscs produce calcitic shell layers, many of these
      broadly classified as "prismatic." Various pteriomorphian bivalves (such as
      oysters, pterioids, and mussels) secrete prismatic microstructures with high
      organic content and clear, strong biological control. However, we present the
      results of a detailed analysis by scanning electron microscopy (SEM),
      thermogravimetric analysis, and electron backscatter diffraction to characterize
      the calcitic prisms in two different clades within the euheterodont bivalves: the
      extant Chama arcana and the extinct rudists. These results show that the form of
      prisms constructed is both closely similar between the two taxa and significantly
      different from those of the pteriomorph bivalves. Most notably, C. arcana and the
      extinct rudists lack the clear organic outer envelopes and uniform polygonal,
      cross-sectional appearance. Instead, they form interdigitating crystals of very
      varied diameters, with some crystals encapsulating others. We advocate retaining
      the term "fibrillar prisms" to classify these euheterodont microstructures. These
      fibrillar prisms are more closely similar to abiotic speleothem deposits than to
      the calcitic prisms of pteriomorph bivalves. We argue that calcite prism growth
      in euheterodonts is dominated by abiotic constraints whereas, in pteriomorphs
      (such as oysters, pterioids, and mussels), it is under strong biological control.

PMID- 28445096
TI  - Protection from Oxidative Stress in Immunocytes of the Colonial Ascidian
      Botryllus schlosseri: Transcript Characterization and Expression Studies.
AB  - Botryllus schlosseri is a cosmopolitan colonial ascidian that undergoes cyclical
      generation changes, or take-overs, during which adult zooids are resorbed and
      replaced by their buds. At take-over, adult tissues undergo diffuse apoptosis and
      effete cells are massively ingested by circulating phagocytes, with a consequent
      increase in oxygen consumption and in production of reactive oxygen species
      (ROS). The latter are responsible for the death of phagocytes involved in the
      clearance of apoptotic cells and corpses by phagocytosis-induced apoptosis.
      However, the majority of phagocytes and hemocytes do not die, even if they
      experience oxidative stress. This fact suggests the presence of detoxification
      mechanisms assuring their protection. To test this assumption, we searched for
      transcripts of genes involved in detoxification in the transcriptome of B.
      schlosseri. We identified and characterized transcripts for Cu/Zn superoxide
      dismutase (SOD), gamma-glutamyl-cysteine ligase modulatory subunit (GCLM),
      glutathione synthase (GS), and two glutathione peroxidases (i.e., GPx3 and GPx5),
      all involved in protection from ROS. We also carried out a phylogenetic analysis
      of the putative amino acid sequences, confirming their similarity to their
      vertebrate counterparts, and studied the location of their mRNAs by in situ
      hybridization on hemocyte monolayers. We also analyzed gene transcription during
      the colonial blastogenetic cycle, which is the interval of time between one take
      over and the next, by qRT-PCR. In addition, we investigated the effects of
      cadmium (Cd), an inducer of oxidative stress, on gene transcription. Our results
      indicated that i) antioxidant gene expression is modulated in the course of the
      blastogenetic cycle and upon exposure to Cd, and ii) hemocytes synthesize both
      enzymatic and nonenzymatic antioxidants, in line with the idea that they
      represent a major detoxification system for ascidians.

PMID- 28445097
TI  - Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Naldemedine for
      the Treatment of Opioid-Induced Constipation in Patients With Cancer.
AB  - Purpose This randomized, double-blind, multicenter study aimed to determine the
      dose of naldemedine, a peripherally-acting MU-opioid receptor antagonist, for
      future trials by comparing the efficacy and safety of three doses of naldemedine
      versus placebo in patients with cancer and opioid-induced constipation. Methods
      Patients >= 18 years old with cancer, an Eastern Cooperative Oncology Group
      performance status <= 2, who had been receiving a stable regimen of opioid
      analgesics for >= 2 weeks, had at least one constipation symptom despite laxative
      use, and no more than five spontaneous bowel movements (SBMs) during the past 14
      days, were randomly assigned (1:1:1:1) to oral, once-daily naldemedine 0.1, 0.2,
      or 0.4 mg, or placebo, for 14 days. The primary end point was change in SBM
      frequency per week from baseline during the treatment period. Secondary end
      points included SBM responder rates, change from baseline in the frequency of SBM
      without straining, and complete SBM. Safety was also assessed. Results Of 227
      patients who were randomly assigned, 225 were assessed for efficacy (naldemedine
      0.1 mg, n = 55; 0.2 mg, n = 58; 0.4 mg, n = 56; placebo, n = 56) and 226 for
      safety. Change in SBM frequency (primary end point) was higher with all
      naldemedine doses versus placebo ( P < .05 for all comparisons), as were SBM
      responder rates and change in complete SBM frequency. Change in SBM frequency
      without straining was significantly improved with naldemedine 0.2 and 0.4 (but
      not 0.1) mg versus placebo (at least P < .05). Treatment-emergent adverse events
      were more common with naldemedine (0.1 mg: 66.1%; 0.2 mg: 67.2%; 0.4 mg: 78.6%)
      than placebo (51.8%); the most common treatment-emergent adverse event was
      diarrhea. Conclusion Fourteen-day treatment with naldemedine significantly
      improved opioid-induced constipation in patients with cancer and was generally
      well tolerated. Naldemedine 0.2 mg was selected for phase III studies.

PMID- 28445098
TI  - Comparative Analysis of Human Epidermal Growth Factor Receptor 2 Testing in
      Breast Cancer According to 2007 and 2013 American Society of Clinical
      Oncology/College of American Pathologists Guideline Recommendations.
AB  - Purpose To study the effect of the 2013 updates to the 2007 American Society of
      Clinical Oncology/College of American Pathologists recommendations for human
      epidermal growth factor receptor 2 (HER2) testing in breast cancer on testing
      patterns and interpretation in a large regional reference laboratory. Patients
      and Methods Patient cases with HER2 testing scores for breast biomarker
      evaluation were selected from our laboratory information system during two 12
      month periods (2012 and 2014). The number of tests performed, type of specimens,
      proportion of HER2-positive and equivocal patient cases, and number of repeat
      tests on subsequent excisional specimens were examined and compared. Results
      Although the number of samples tested increased between 2012 and 2014 (2,201 v
      2,558 patient cases; 2,278 v 2,659 tumors), HER2 positivity remained constant
      (15.7% v 15.5%, respectively). The number of repeat tests performed within 6
      months more than doubled (122 [5.5%) of 2,201 v 302 [11.8%] of 2,558; P < .001),
      and the proportion of immunohistochemistry (IHC) 2+ tumors was significantly
      lower in 2014 than in 2012 (20.3% v 25.3%; P < .001). However, the proportion of
      patient cases with unresolved HER2 statuses (equivocal by IHC and in situ
      hybridization) was significantly higher in 2014 (four of 2,278 v 90 of 2,660; P <
      .001). Conclusion Our findings indicate that the 2013 updates to the American
      Society of Clinical Oncology/College of American Pathologists recommendations for
      HER2 testing in breast cancer did not affect the overall HER2-positivity rate or
      the proportion of patients eligible for HER2-targeted therapy. The proportion of
      tests and repeat tests performed increased, as did the number of patient cases
      categorized as ISH equivocal. The benefit of targeted therapy in the equivocal
      group is not proven, so targeted therapy should not be considered for patients in
      this category which should be redefined in future iterations of the
      recommendations.

PMID- 28445099
TI  - Laparoscopic Spigelian Hernia Repair: Intraperitoneal Onlay Mesh-Plus Technique
      Video Presentation.
AB  - BACKGROUND: Spigelian hernia represents a rare entity. Traditionally, it was
      repaired by the open technique. Various laparoscopic techniques have emerged
      periodically. Most laparoscopic repairs use the technique of placing an
      intraperitoneal onlay mesh (IPOM). There is currently a tendency to close the
      hernia defect. METHODS: A 68-year-old man was admitted to our hospital
      complaining of vague abdominal pain and discomfort. Physical examination revealed
      a bulky palpable mass on the left side of the patient. Computed tomography of
      abdomen revealed a left-sided incarcerated spigelian hernia containing bowel. The
      aim of this study was to report an educational video providing a successful
      laparoscopic IPOM-plus technique with muscles approximation of spigelian hernia
      repair step by step. RESULTS: Total operative time was 120 minutes. The
      postoperative period was uneventful. The patient reported no pain and the
      cosmetic result was excellent. No bulging or seroma was noted. The patient was
      discharged on postoperative day 1. CONCLUSION: The IPOM-plus technique may
      improve the outcome of spigelian hernia repair.

PMID- 28445100
TI  - REMAP: A Framework for Goals of Care Conversations.
AB  - Conversations regarding goals of care with patients who have advanced cancer
      still occur too late, and oncologists say they lack the training to have these
      conversations effectively. Experts recommend a number of strategies when having
      these discussions, including discussing prognosis, responding to patient emotion,
      exploring values, and often making a recommendation for medical treatments that
      fit those values. To help learners, from residents to attending oncologists,
      learn these complex conversational skills, we have developed a framework with a
      mnemonic, REMAP: Reframe, Expect emotion, Map out patient goals, Align with
      goals, and Propose a plan. In the reframe step, the oncologist provides a big
      picture "headline" that lets the patient know things are in a different place.
      This is followed by actively attending to the patient's emotional response
      (expect emotion). Then, to map the patient's goals, the oncologist asks open
      ended questions that are designed to help the patient think about the values that
      should guide his or her treatment. The oncologist then aligns with those values
      by explicitly reflecting them back to the patient. If the patient gives
      permission, the oncologist will then use those values to propose a medical plan
      that matches patient values. The processes underlying REMAP encourage oncologists
      and other clinicians to seek to understand and remain flexible, adapting their
      recommendations to what they hear from the patient, with ongoing revision based
      on the shared decision-making process. This will lead to patient-centered
      decisions that promote better end-of-life care.

PMID- 28445101
TI  - Second-Line Hormonal Therapy for Men With Chemotherapy-Naive Castration-Resistant
      Prostate Cancer: American Society of Clinical Oncology Provisional Clinical
      Opinion Summary.

PMID- 28445102
TI  - Journey of Generic Imatinib: A Case Study in Oncology Drug Pricing.

PMID- 28445103
TI  - Whose Data Are They Anyway? Can a Patient Perspective Advance the Data-Sharing
      Debate?

PMID- 28445104
TI  - Endoscopic Ultrasound-Guided Direct Portal Pressure Measurement Using a Digital
      Pressure Wire with Real-Time Remote Display: A Survival Study.
AB  - BACKGROUND: Portal hypertension is necessary for the development of most clinical
      complications of cirrhosis. We recently reported a novel, endoscopic ultrasound
      (EUS)-guided technique for direct portal pressure measurements using a digital
      pressure wire. AIMS: The aims of this study were to (1) evaluate safety in an
      animal survival model and (2) compare direct portal vein (PV) versus transhepatic
      access of a first-order venule. MATERIALS AND METHODS: Yorkshire pigs, weighing
      40-55 kg. Procedures were performed under general anesthesia. PV was identified
      using a linear array echoendoscope and accessed with a 22-G fine needle
      aspiration needle preloaded with a digital pressure wire. Access was confirmed by
      portal venography. Mean digital pressure measurements were recorded over 30
      seconds, and again after accessing a first-order portal venule in a transhepatic
      manner. Procedure times and video logs were maintained throughout. Animals were
      survived for 2 weeks. Repeat portal pressure measurements were performed before
      euthanasia and necropsy. RESULTS: EUS-guided portal pressure measurements ranged
      from 3 to 11 mm Hg (mean 6.1) and were performed in a mean time of 214 seconds.
      There was no difference in measurement between the PV and first-order venule, or
      between baseline and 2-week follow-up. Five of 5 animals survived without
      incident. On necropsy, there was no evidence of thrombus or hemorrhage.
      CONCLUSIONS: This study represents the first survival study after EUS-guided
      direct portal pressure measurements using a digital pressure wire. This method
      appears safe, straightforward, and precise. Measurements of the PV and a first
      order portal venule appear equivalent, and serial measurement seems feasible.

PMID- 28445105
TI  - Short-Term Outcomes of Minimally Invasive Esophagectomy for Carcinoma In Patients
      with Liver Cirrhosis.
AB  - BACKGROUND: Open esophagectomy is a high-risk procedure in patients with liver
      cirrhosis. With the advent of minimally invasive surgical techniques, the overall
      morbidity and mortality rates of esophagectomy have decreased. The aim of this
      study was to describe short-term outcomes of minimally invasive esophagectomy in
      patients with proven liver cirrhosis. METHODS: Retrospective observational cohort
      study. Demographics, preoperative clinical characteristics, and outcomes of
      patients undergoing minimally invasive esophagectomy for carcinoma were analyzed.
      Patients with concomitant liver cirrhosis were compared to patients without liver
      cirrhosis undergoing similar surgical procedures. In addition, variables possibly
      associated with postoperative morbidity and mortality in patients with cirrhosis
      were investigated. RESULTS: Out of 443 patients undergoing minimally invasive
      esophagectomy, 18 (4.1%) had concomitant liver cirrhosis. Demographics and
      preoperative clinical variables were similar in the 2 patient groups. While the
      overall morbidity rate was similar, the 90-day mortality rate was significantly
      higher in patients with liver cirrhosis (P = .023). There was a significantly
      higher rate of sepsis and anastomotic, respiratory, and hemorrhagic complications
      in patients with liver cirrhosis who died in the postoperative period.
      CONCLUSIONS: Minimally invasive esophagectomy is feasible in patients with liver
      cirrhosis. Future strategies should focus on total minimally invasive procedures
      and early recognition of surgical complications.

PMID- 28445106
TI  - Tension-Free Inlay Repair of Large Hiatal Hernias Using Dual-Sided Composite
      PTFE/ePTFE Meshes in Laparoscopic Surgery for Gastroesophageal Reflux Disease.
AB  - BACKGROUND: Patients with gastroesophageal reflux disease (GERD) also frequently
      suffer from concomitant hiatal hernia. It has been described that a preoperative
      hiatal hernia of >=3 cm is associated with a more than threefold relative risk
      for reflux symptom recurrence after fundoplication without mesh reinforcement. In
      this report, we describe our experience with the implantation of dual-sided
      composite PTFE/ePTFE meshes in a tension-free fashion during laparoscopic
      antireflux surgery (LARS). METHODS: A prospective database containing data of all
      patients undergoing LARS and hiatal hernia repair with mesh implantation from
      January 2009 until December 2014 was interrogated. Ten patients with preoperative
      esophageal high resolution manometry and 24-hour pH impedance monitoring because
      of symptoms suggestive of GERD who received hiatal repair using dual-sided meshes
      in inlay technique were identified and included in this analysis. RESULTS: There
      were no conversions to open surgery in the study group. Median operative time was
      138 minutes (interquartile range Q1-Q3: 119-151 minutes) and average length of
      postoperative stay was 3.5 days (interquartile range Q1-Q3: 2.3-4.0 days). During
      a median follow-up period of 43.3 months (interquartile range Q1-Q3: 18.9-47.1
      months), no redo operations had to be performed. Noteworthy, 2 patients
      complained about dysphagia (20%) during follow-up, but symptoms resolved after
      endoscopic interventions. CONCLUSIONS: Tension-free inlay repair of large hiatal
      hernias using dual-sided composite PTFE/ePTFE meshes during LARS provides
      promising results. It provides satisfactory symptom relief and prolonged control
      of GERD. Further studies to validate its efficiency in a larger collective are
      needed.

PMID- 28445107
TI  - Hypodermal Adipose Tissue Sonoelastography for Monitoring Treatment Response in
      Patients with Plaque Psoriasis.
AB  - BACKGROUND: Psoriasis (PsO) is a multifactorial chronic and relapsing skin
      disease that affects about 125 million people in the world. Several studies have
      demonstrated the link between adipose tissue, inflammation, and PsO. The purpose
      of our study is to evaluate hypodermal adipose tissue inflammation underneath PsO
      plaques quantifying tissue elasticity with sonoelastography before and after
      treatment. The study was conducted at the Department of Dermatology of the
      University of "Rome Tor Vergata" and Department of Radiology of the University of
      "Rome Tor Vergata." METHODS: We enrolled 60 patients with plaque PsO and a PASI
      score of >=5 divided in three groups of treatment: biologic drugs therapy (Group
      A), systemic therapy with DMARDS (Group B), and topic therapy (Group C). Each
      Patient underwent sonoelastography examination (TE: transient elastography) at
      baseline (T0) and after 1 month (T1) of treatment. The region of interest (ROI) 5
      * 5 mm area and the strain ratio was obtained dividing muscular elasticity
      (referral tissue) by hypodermal elasticity. RESULTS: The difference between T0
      and T1 was referred as Delta strain. Sonoelastography is able to identify
      hypodermal adipose tissue involvement in plaque PsO and on the basis of our
      experience it could represent a valid method to assess early therapy response in
      patient with plaque PsO. CONCLUSIONS: This is the first report regarding the use
      of sonoelastography in psoriatic patients. Sonoelastography is easy to use,
      rapid, and is a portable technique that does not use ionizing radiation. The
      result showed the mean lesional strain ratio significantly higher than the
      nonlesional one at baseline examination. In the future, the role of ultrasound
      sonoelastography is likely to be complementary to conventional imaging techniques
      in providing an additional tool.

PMID- 28445108
TI  - Manganese Provision in Parenteral Nutrition: An Update.
AB  - Manganese (Mn) is an essential micronutrient required for the activity of
      metalloenzymes. It is an essential component of parenteral nutrition (PN), but
      requirements are low. Mn status is difficult to assess, with the commonest method
      being measurement of its concentration in whole blood. This method has
      limitations, including artifactually high concentrations resulting from
      contamination of specimen tubes. Mn toxicity is a well-recognized complication of
      PN, the risk of which increases if there is cholestasis or if the patient has
      received high doses. It usually presents with parkinsonian-like symptoms but may
      be detected presymptomatically as hypermanganesemia or as increased signal
      intensity of the basal ganglia upon T1-weighted magnetic resonance imaging.
      Caution is necessary when providing Mn for patients on long-term PN (>1 month).
      It is advisable to withhold supplementation if hypermanganesemia or cholestasis
      develops. Deficiency of Mn is rare in patients treated with PN. PN regimens are
      contaminated with Mn in amounts likely to meet requirements. Consequently, it is
      debated whether PN should be routinely supplemented with Mn. The currently
      recommended dose of Mn in adults treated with PN is 55 MUg/d, but the doses
      provided by most currently available multi-trace element products exceed this. In
      response to calls for new products to be developed, 2 new multi-trace element
      products are currently available in Europe that provide Mn doses of 55 MUg/d.
      Once these products are in general use, it is likely that the incidence of Mn
      toxicity will decrease.

PMID- 28445109
TI  - Distinct Prevalence of Drug-Resistant Tuberculosis in Gansu, China: A
      Retrospective Study on Drug Susceptibility Profiles Between 2010 and 2014.
AB  - Limited knowledge is available on regional distribution of antituberculosis (TB)
      drug resistance and on province-specific time-trends in TB drug susceptibility in
      China. To obtain the latest information about the dynamics of drug-resistant TB
      in Gansu province, we conducted a retrospective study and analyzed data on drug
      resistance among new TB cases diagnosed between June 2010 and May 2014 in Gansu,
      China. The data were collected from the only TB surveillance and treatment
      hospital in Gansu and, therefore, represented the epidemiology of TB in the
      province. The drug resistance was defined based on diagnostic drug susceptibility
      testing. Overall, 17.3% of TB new cases diagnosed during 2010 to 2014 in Gansu
      presented resistance to at least one anti-TB drug. And a total of 2.9% of new TB
      cases have multidrug resistance. The prevalence of multidrug-resistant TB in
      Gansu was found to resurge after 2013 (2.0%) after a steady decline between 2010
      and 2012 (from 7.1% to 1.2%). The drug resistance patterns of TB and their
      revolution trends in Gansu differed from other regions of China. We report the
      first epidemiological description of drug-resistant TB in Gansu, which is
      distinct when compared to other regions. Our data demonstrate that the
      distribution of drug-resistant TB varies to a great extent among different
      geographic regions. And the results of our study greatly suggest that the
      implementation of individualized TB management and regimen policy based on the
      regional epidemiology of TB drug susceptibility is highly required.

PMID- 28445110
TI  - Normobaric hypoxia increases the growth hormone response to maximal resistance
      exercise in trained men.
AB  - This study examined the effect of hypoxia on growth hormone (GH) release during
      an acute bout of high-intensity, low-volume resistance exercise. Using a single
      blinded, randomised crossover design, 16 resistance-trained males completed two
      resistance exercise sessions in normobaric hypoxia (HYP; inspiratory oxygen
      fraction, (FiO2) 0.12, arterial oxygen saturation (SpO2) 82 +/- 2%) and normoxia
      (NOR; FiO2 0.21, SpO2 98 +/- 0%). Each session consisted of five sets of three
      repetitions of 45 degrees  leg press and bench press at 85% of one repetition
      maximum. Heart rate, SpO2, and electromyographic activity (EMG) of the vastus
      lateralis muscle were measured throughout the protocol. Serum lactate and GH
      levels were determined pre-exposure, and at 5, 15, 30 and 60 min post-exercise.
      Differences in mean and integrated EMG between HYP and NOR treatments were
      unclear. However, there was an important increase in the peak levels and area
      under the curve of both lactate (HYP 5.8 +/- 1.8 v NOR 3.9 +/- 1.1 mmol.L-1 and
      HYP 138.7 +/- 33.1 v NOR 105.8 +/- 20.8 min.mmol.L-1) and GH (HYP 4.4 +/- 3.1 v
      NOR 2.1 +/- 2.5 ng.mL-1 and HYP 117.7 +/- 86.9 v NOR 72.9 +/- 85.3 min.ng.mL-1)
      in response to HYP. These results suggest that performing high-intensity
      resistance exercise in a hypoxic environment may provide a beneficial endocrine
      response without compromising the neuromuscular activation required for maximal
      strength development.

PMID- 28445111
TI  - Review of Separation Technologies for Treating Pesticide-Contaminated Soil.
AB  - Pesticide contamination results from manufacturing, improper storage, handling,
      or disposal of pesticides, and from agricultural processes. Since most pesticides
      are mixtures of different compounds, selecting a remedy for pesticide
      contaminated soils can be a complicated process. The various available treatment
      options for remediation fall into three broad categories: containment
      immobilization, separation-concentration, and destruction. This paper categorizes
      pesticides into waste groups based on available treatment options and provides a
      review of separation treatment options that have been demonstrated to-or show
      potential to- treat pesticide-contaminated soil. Technologies include radio
      frequency heating, soil washing, thermal desorp-tion, and solvent extraction.

PMID- 28445114
TI  - Improvement of Air Quality in a Small Indoor Ice Arena by Effective Emission
      Control in Ice Resurfacers.
AB  - The effectiveness of a new emission control system in the ice resurfacer was
      tested in an exhaust gas emission laboratory, and the improvement of the air
      quality in a small, enclosed ice arena was demonstrated in a 4.5-month follow-up
      study. The emission control system consisted of a lambda sensor-controlled fuel
      supply and a three-way metallic catalyst that were applied to a propane-fueled
      resurfacer. In the laboratory tests, the engine emissions of carbon monoxide
      (CO), hydrocarbons (HC), and nitrogen oxides (NO ) reduced simultaneously by 91,
      90, and 96%, respectively. During the air quality follow-up the median 1-hour
      average nitrogen dioxide (N02) concentration inside the ice arena decreased from
      430 ug/m3 (230ppb) to 58 ug/m3 (31 ppb), and that of CO decreased from 4.4 mg/m3
      (3.8 ppm) to 1.5 mg/m3 (1.3 ppm). The new emission control system proved to be a
      feasible, reliable, and effective means to improve the indoor air quality in the
      ice arena. However, continuous mechanical ventilation was necessary during all
      business hours in order to achieve and maintain a fully acceptable air quality
      with this technology.

PMID- 28445115
TI  - Development of Emission Factors for Ethylene-Vinyl Acetate and Ethylene-Methyl
      Acrylate Copolymer Processing.
AB  - Emission factors for selected volatile organic compounds (VOCs) and particulate
      emissions were developed over a range of temperatures during extrusion of three
      mixtures of ethylene-vinyl acetate (EVA) copolymers and two mixtures of ethylene
      methyl acrylate (EMA) copolymers. A mixture of low-density polyethylene (LDPE)
      resins was used as a control. EVAs with 9, 18, and 28% vinyl acetate (VA) were
      used. The EMA mixtures were both 20% methyl acrylate. A small commercial extruder
      was used. Polymer melt temperatures were run at 340  degrees F for LDPE and both
      18 and 28% EVAs. The 9% EVA mixture was extruded at 435  degrees F melt
      temperature. The EMA mixtures were extruded at 350 and 565  degrees F melt
      temperatures. An emission rate for each substance was calculated, measured, and
      reported as pounds released to the atmosphere per million pounds of polymer
      processed [ppm (wt/wt)]. Based on production volumes, these emission factors can
      be used by processors to estimate emission quantities from EVA and EMA extrusion
      operations that are similar to the resins and the conditions used in the study.

PMID- 28445116
TI  - Analysis of PM10 Trends in the United States from 1988 through 1995.
AB  - Because the U. S. Environmental Protection Agency (EPA) has changed the National
      Ambient Air Quality Standards (NAAQS) for ambient particulate matter (PM), there
      is a great deal of interest in determining recent PM trends. This paper examines
      trends in PM10 (i.e., particulate matter less than 10 micrometers in diameter)
      for areas of the United States based on their attainment status-for PM10 and
      ozone nonattainment and attainment areas. The analysis also focuses on urban,
      suburban, and rural areas, and eastern and western areas. The time period of
      evaluation is from 1988 through 1995. To shed further light on the ambient PM10
      trends, trends in ambient SO2, NO2, and volatile organic compounds (VOCs) are
      also analyzed. Finally, trends in emission inventories of SO2, NOx, VOCs, and
      PM10 are evaluated. Results of the analysis show that widespread and similar
      reductions in PM10 levels have occurred over the last seven years. Annual
      reductions range from 3.0% to 3.8%, with the greatest reductions coming in PM10
      nonattainment areas, but with very significant reductions also in PM10 attainment
      areas, ozone attainment areas, and rural areas. The widespread reductions appear
      to be due to a set of controls or common factors that are having a fairly uniform
      effect in all of the areas. The consistency of the reductions in different areas
      suggests that the reductions may also be primarily in the fine particles (i.e.,
      those less than 2.5 micrometers in diameter, or PM2.5), which are more readily
      transported than coarse particles.

PMID- 28445117
TI  - The Use of Photochemical Indicators to Evaluate Ozone-NOx-Hydrocarbon
      Sensitivity: Case Studies from Atlanta, New York, and Los Angeles.
AB  - This study examines the use of ambient measurements of a number of "photochemical
      indicators" as a basis for determining ozone-NOx-hydrocarbon sensitivity and for
      evaluating the performance of ozone models. The successful photochemical
      indicators are: 03/NO , 03/NOz (where NOz = NOy-NOx), 03/HN03, H202/HN03, and
      H202/NOz. Results of Urban Airshed Model (UAM-IV) simulations for Atlanta, GA,
      New York, NY, and Los Angeles, CA, show that high values of these species ratios
      are correlated with NOx-sensitive chemistry and low values are associated with
      reactive organic gases (ROG)-sen-sitive chemistry. Correlations between measured
      03 and NO in Atlanta and between 03 and NOz in Los Angeles are consistent with
      theory and reflect the difference between likely NOx-sensitive chemistry in
      Atlanta and hydrocarbon-sensitive chemistry in Los Angeles. Measured 03, NOx and
      NO are used to evaluate model performance during two air pollution events in
      Atlanta and Los Angeles. The performance evaluation includes model scenarios for
      each city with different anthropogenic and biogenic emission rates and different
      NOx-ROG sensitivity predictions. Simulations with different NOx-ROG chemistry are
      found to give similar predictions for peak ozone but different values for
      photochemical indicators. Comparison with measured values of photochemical
      indicators provides a more stringent test of model performance than evaluation
      versus observed ozone.

PMID- 28445118
TI  - Curbside Collection of Recyclable Material: Simulation of Collection Activities
      and Estimation of Vehicle and Labor Needs.
AB  - This paper presents a mathematical model that can be used to estimate the time
      required to collect recyclable material (route time) by simulating the activities
      of a collection vehicle driving over its route. Data obtained by observing the
      collection of recyclable material in The Village, OK, were used to determine
      parameters for the model. The validity and robustness of the model were tested by
      comparing model-predicted route time to observed route time. The model was able
      to predict route time within 8%. Simulation procedures are presented that can be
      used to estimate route time under conditions not actually ob-served-for instance,
      very low or high rates of material being set out for collection. The simulation
      procedures, incorporating randomly assigned set-out distributions, indicate that
      set-out distribution (proximity of houses setting out materials) has little
      effect on route time. Vehicle and labor needs for the curbside collection of
      recyclable material in a hypothetical town are estimated to demonstrate a
      practical application of the simulation procedure. The results indicate that if
      set-out rate were to increase from 20% to 30%, labor needs would increase by 34%
      and an additional vehicle would be needed to serve the same number of households.
      Increasing set-out rate from 20% to 40% would result in a labor requirement
      increase of 68%. Calculations such as these are particularly significant if a
      program to increase participation is being considered.

PMID- 28445119
TI  - Isothermal Oxidation of White Phosphorus Dispersed in Water in a Stirred-Tank
      Reactor.
AB  - A global, first-order kinetic model was found to fit the data for the isothermal
      wet oxidation of elemental white phosphorus (P4) in a batch, stirred-tank
      reactor. The initial concentration of white phosphorus solids was held constant
      at 1 g/L and an air flow of 2.0 standard liters per minute was used to supply the
      oxygen for the reaction. A CD6-like turbine and an A2 impeller were evaluated at
      speeds from 1000-2250 rpm. For the CD6-like turbine, mass transfer effects were
      assumed to be eliminated above 2000 rpm. Thus, the CD6-like turbine with a speed
      of 2250 rpm was selected for the isothermal studies. Particle size and
      temperature were varied. For the isothermal conditions, the first order kinetic
      constant varied from 0.022 min-1 at 46  degrees C to 0.078 min-1 at 80  degrees
      C. The apparent activation energy was 6.78 kcal/mol. Oxygen reacted with the
      suspended P4 particles forming oxides of phosphorus, primarily phosphorus
      pentoxide (P4010 or P2 O5). Some of the P2O5 reacted with the water to form PO43-
      as the primary product of white phosphorus oxidation. The amount of phosphorus
      pentoxide absorbed in the water increased with temperature. The rate of phosphate
      formation followed zero order kinetics and was independent of particle size. As
      the temperature increased, the ratio of PO4/ PO3 increased. This observation and
      the apparently low activation energy suggest that diffusion effects may not have
      been eliminated completely.

PMID- 28445120
TI  - Removal of PCBs from a Contaminated Soil Using CF-Systems(r) Solvent Extraction
      Process.
AB  - The U.S. Environmental Protection Agency's (EPA) Superfund Technical Assistance
      Response Team (START) in cooperation with EPA's Superfund Innovative Technology
      Evaluation (SITE) program evaluated a pilot scale solvent extraction process
      developed by CF-Systems. This process uses liquefied propane to extract organic
      contaminants from soils, sludges, and sediments. A pilot-scale evaluation was
      conducted in Golden, CO at Hazen Research, Inc., using CF-Systems' trailer
      mounted organics extraction unit. Approximately 1,000 pounds of soil, with an
      average poly-chlorinated biphenyl (PCB) concentration of 260 mg/kg, was obtained
      from a remote Superfund site. Six 100-pound batches of the contaminated soil were
      extracted using multiple extraction sequences. Three of the six batch runs were
      subjected to three extraction sequences each, so that process variability could
      be evaluated. Results showed that PCB removal efficiencies varied between 91.4
      and 99.4%, with the propane-extracted soils retaining low concentrations of PCBs
      (19.0-1.8 mg/kg). Removal efficiencies of oil and grease (O&G) were found to be
      96.0 to 99.6% with propane-extracted soils retaining O&G concentrations from 279
      to <20 mg/kg. Overall extraction efficiency was found to be dependant upon the
      numberof extraction cycles used.

PMID- 28445121
TI  - Characterization of Air Quality Problems in Five Finnish Indoor Ice Arenas.
AB  - The air quality in five Finnish ice arenas with different volumes, ventilation
      systems, and resurfacer power sources (propane, gasoline, electric) was monitored
      during a usual training evening and a standardized, simulated ice hockey game.
      The measurements included continuous recording of carbon monoxide (CO), nitric
      oxide (NO), and nitrogen dioxide (NO2) concentrations, and sampling and analysis
      of volatile organic compounds (VOCs). Emissions from the ice resurfacers with
      combustion engines caused indoor air quality problems in all ice arenas. The
      highest 1-hour average CO and NO2 concentrations ranged from 20 to 33 mg/m3 (17
      to 29 ppm) and 270 to 7440 ug/m3 (0.14 to 3.96 ppm), respectively. The 3-hour
      total VOC concentrations ranged from 150 to 1200 ug/m3. The highest CO and VOC
      levels were measured in the arena in which a gasoline-fueled resurfacer was used.
      The highest NO2 levels were measured in small ice arenas with propane-fueled ice
      resurfacers and insufficient ventilation. In these arenas, the indoor NO2 levels
      were about 100 times the levels measured in ambient outdoor air, and the highest
      1-hour concentrations were about 20 times the national and World Health
      Organization (WHO) health-based air quality guidelines. The air quality was fully
      acceptable only in the arena with an electric resurfacer. The present study
      showed that the air quality problems of indoor ice arenas may vary with the fuel
      type of resurfacer and the volume and ventilation of arena building. It also
      confirmed that there are severe air quality problems in Finnish ice arenas
      similar to those previously described in North America.

PMID- 28445112
TI  - Tracking the Evolution of Non-Small-Cell Lung Cancer.
AB  - BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), data on
      intratumor heterogeneity and cancer genome evolution have been limited to small
      retrospective cohorts. We wanted to prospectively investigate intratumor
      heterogeneity in relation to clinical outcome and to determine the clonal nature
      of driver events and evolutionary processes in early-stage NSCLC. METHODS: In
      this prospective cohort study, we performed multiregion whole-exome sequencing on
      100 early-stage NSCLC tumors that had been resected before systemic therapy. We
      sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain
      a census of clonal and subclonal events, and assess the relationship between
      intratumor heterogeneity and recurrence-free survival. RESULTS: We observed
      widespread intratumor heterogeneity for both somatic copy-number alterations and
      mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always
      clonal. However, heterogeneous driver alterations that occurred later in
      evolution were found in more than 75% of the tumors and were common in PIK3CA and
      NF1 and in genes that are involved in chromatin modification and DNA damage
      response and repair. Genome doubling and ongoing dynamic chromosomal instability
      were associated with intratumor heterogeneity and resulted in parallel evolution
      of driver somatic copy-number alterations, including amplifications in CDK4,
      FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an
      increased risk of recurrence or death (hazard ratio, 4.9; P=4.4*10-4), which
      remained significant in multivariate analysis. CONCLUSIONS: Intratumor
      heterogeneity mediated through chromosome instability was associated with an
      increased risk of recurrence or death, a finding that supports the potential
      value of chromosome instability as a prognostic predictor. (Funded by Cancer
      Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).

PMID- 28445122
TI  - Importation of Zika Virus from Vietnam to Japan, November 2016.
AB  - We report a case of Zika virus infection that was imported to Japan by a traveler
      returning from Vietnam. We detected Zika virus RNA in the patient's saliva,
      urine, and whole blood. In the Zika virus strain isolated from the urine, we
      found clearly smaller plaques than in previous strains.

PMID- 28445123
TI  - Changes in the free-energy landscape of p38alpha MAP kinase through its canonical
      activation and binding events as studied by enhanced molecular dynamics
      simulations.
AB  - p38alpha is a Ser/Thr protein kinase involved in a variety of cellular processes
      and pathological conditions, which makes it a promising pharmacological target.
      Although the activity of the enzyme is highly regulated, its molecular mechanism
      of activation remains largely unexplained, even after decades of research. By
      using state-of-the-art molecular dynamics simulations, we decipher the key
      elements of the complex molecular mechanism refined by evolution to allow for a
      fine tuning of p38alpha kinase activity. Our study describes for the first time
      the molecular effects of different regulators of the enzymatic activity, and
      provides an integrative picture of the activation mechanism that explains the
      seemingly contradictory X-ray and NMR data.

PMID- 28445124
TI  - A novel triazolonaphthalimide induces apoptosis and inhibits tumor growth by
      targeting DNA and DNA-associated processes.
AB  - DNA and DNA-associated processes have been classes of the most important targets
      of chemotherapeutic drugs. As classic DNA intercalators and topoisomerase
      inhibitors, naphthalimides have been extensively investigated as potential anti
      cancer drugs. We recently synthesized a novel series of triazolonaphthalimides
      with excellent anti-cancer activities. In the present study, one of the most
      potent triazolonaphthalimides, LSS-11, was investigated. LSS-11 bound to DNA in
      vitro and in cell mainly by minor groove binding and significantly increased the
      stability of DNA, which could be fundamental for the biological activities of LSS
      11. In addition to inhibiting DNA topoisomerase II-catalyzed decatenation of
      knotted circulated DNA, LSS-11 dramatically inhibited DNA replication mediated by
      polymerase chain reaction and isothermal helicase-dependent amplification, as
      well as the expression of luciferase driven by a minimal TA promoter in cell.
      Furthermore, LSS-11 exhibited strong cytotoxicity in selected human colon cancer
      cell lines by inducing cell cycle arrest and apoptosis, which was accompanied by
      DNA damage response. Finally, LSS-11 potently inhibited the growth of S180 murine
      sarcoma and SW480 human colorectal cancer xenografts in vivo without significant
      major toxicities. These results suggest that LSS-11 deserves further research and
      development as a novel anti-cancer agent, and provided new understandings of
      mechanisms by which LSS-11 inhibited multiple DNA-associated processes and tumor
      growth.

PMID- 28445125
TI  - Intratumoral heterogeneity analysis reveals hidden associations between protein
      expression losses and patient survival in clear cell renal cell carcinoma.
AB  - Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is
      not known whether it has utility in finding associations between protein
      expression and clinical parameters. We used ITH that is detected by
      immunohistochemistry (IHC) to aid the association analysis between the loss of
      SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage)
      were used to generate tissue microarray (TMA). Four foci from different regions
      of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2,
      SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker
      losses with patho-clinical parameters. Categorical variables were compared
      between groups using Fisher's exact tests. Univariate and multivariable analyses
      were used to correlate biomarker changes and patient survivals. Multivariable
      analyses were performed by constructing decision trees using the classification
      and regression trees (CART) methodology. IHC detected widespread ITH in ccRCC
      tumors. The statistical analysis of the "Truncal loss" (root loss) found
      additional correlations between biomarker losses and tumor stages than the
      traditional "Loss in tumor (total)". Losses of SMARCA4 or SMARCA2 significantly
      improved prognosis for overall survival (OS). Losses of PBRM1, ARID1A or SETD2
      had the opposite effect. Thus "Truncal Loss" analysis revealed hidden links
      between protein losses and patient survival in ccRCC.

PMID- 28445126
TI  - Clinical features and surgical treatment of sacral schwannomas.
AB  - BACKGROUND: Sacral schwannoma is relatively rare and both the early diagnosis and
      appropriate treatment of sacral schwannomas are equally very challenging.
      METHODS: 11 sacral schwannoma cases operated at the Second Affiliated Hospital,
      School of Medicine, Zhejiang University, from 2012 to 2016, were investigated
      retrospectively and 10 were followed up. All patients were assessed with X-ray,
      CT and MRI, and underwent an intralesional excision. RESULTS: One patient was
      male, nine were female and the average age was 48 (ranging between 31 and 63).
      Three patients suffered from back and leg pain, and seven had no obvious
      symptoms. The average blood loss during surgery was 980ml (ranging between 100
      and 2,000ml). Six patients underwent preoperative biopsy. The surgeries were
      performed via the combination of an anterior and posterior approach in two
      patients, a posterior approach in seven patients, and an anterior approach in one
      patient. Residual tumors were not detected in all patients after surgery.
      Unfortunately, the postoperative complications occurred in three patients, namely
      bowel and bladder dysfunction (two patients) and cerebrospinal fluid leakage with
      secondary intracranial infection (one patient). The average follow-up was 22.7
      months (8-44 months). All patients were relieved from preoperative symptoms after
      the last follow-up. CONCLUSIONS: The typical findings of our cases in MRI were a
      well-circumscribed lesion with a heterogenous signal intensity on T2-weighted
      image, which may be helpful for preoperative decision-making. Intralesional
      excision can be successfully performed using single anterior or single posterior
      or both, and is an important procedure in the treatment of sacral schwannomas.

PMID- 28445127
TI  - Mutation of the Sp1 binding site in the 5' flanking region of SRY causes sex
      reversal in rabbits.
AB  - Sex-determining region Y is a crucial gene that initiates male sex determination
      in mammals. Mutations of the Sp1-binding site in the 5' flanking region of SRY
      are associated with clinical male-to-female sex reversal syndrome, although such
      occurrences are rare and, until now, have not been reported in animal models. In
      this study, we mutated Sp1-binding sites in the 5' flanking region of the rabbit
      SRY gene using the CRISPR/Cas9 system. As expected, the SRY-Sp1 knockout rabbits
      had female external and internal genitalia and exhibited normal female copulatory
      behaviors, but they were infertile, and the adults displayed reduced follicles.
      Interestingly, we successfully obtained offspring from sex-reversed SRY-Sp1
      knockout rabbits using embryo transfer. In summary, our study demonstrates that
      Sp1 is a major regulator in SRY gene transcription, and mutations of the Sp1
      binding sites (Sp1-B and Sp1-C) in the 5' flanking region of SRY induce sex
      reversal in rabbits, which can be used as targets for clinical research of male
      to-female sex reversal syndrome. Additionally, we provide the first evidence that
      sex reversal syndrome patients have the potential to become pregnant with the use
      of embryo transfer.

PMID- 28445128
TI  - 3-Dimensional micropillar drug screening identifies FGFR2-IIIC overexpression as
      a potential target in metastatic giant cell tumor.
AB  - We established two patient derived tumor cells (PDCs) from right and left
      pulmonary metastatic lesions respectively of a patient with giant cell tumor. At
      that time, patient-derived tumor cells from right and left surgical specimens
      were collected and cultured. High-throughput screening (HTS) for 24 drugs was
      conducted with a micropillar/microwell chip platform using giant cell tumor PDCs.
      Using 6 doses per drug in 6 replicates for giant cell tumor PDCs, the dose
      response curves and corresponding IC50 values were calculated from the scanned
      images using the S+ Chip Analyzer. A sensitive response was more significantly
      achieved for AZD4547 (FGFR2 inhibitor) in giant cell tumor PDCs originated from
      the right pulmonary nodule under the micropillar/microwell chip platform using 3D
      culture. This sensitivity was consistent with the target expression patterns of
      giant cell tumor PDCs (FGFR2-IIIC mRNA expression in giant cell tumor PDCs
      originated from the right pulmonary nodule was increased significantly as
      compared to those originated from left). However, in a conventional 2D cultured
      MTT assay, there was no difference for IC50 values of AZD4547 between giant cell
      tumor PDCs originated from right and left pulmonary nodules. An HTS platform
      based on 3D culture on micropillar/microwell chips and PDC models could be
      applied as a useful preclinical tool to evaluate the intrapatient tumor/response
      heterogeneity. This platform based on 3D culture might reflect far better the
      relation between the tumor-biology and the matched targeted agent as compared to
      a conventional 2D cultured MTT assay.

PMID- 28445129
TI  - Tea consumption and the risk of ovarian cancer: A meta-analysis of
      epidemiological studies.
AB  - A large number of epidemiological studies have provided conflicting results about
      the relationship between tea consumption and ovarian cancer. This study aimed to
      clarify the association between tea consumption and ovarian cancer. A literature
      search of the MEDICINE, Scopus, PubMed, and Web of Science databases was
      performed in April 2016. A total of 18 (11 case-control and 7 cohort) studies,
      representing data for 701,857 female subjects including 8,683 ovarian cancer
      cases, were included in the meta-analysis. A random-effects meta-analysis was
      used to compute the pooled relative risks (RR), meta regression, and publication
      bias, and heterogeneity analyses were performed for the included trials. We found
      that tea consumption had a significant protective effect against ovarian cancer
      (relative risk [RR] = 0.86; 95% confidence interval [CI]: 0.76, 0.96). The
      relationship was confirmed particularly after adjusting for family history of
      cancer (RR = 0.85; 95% CI: 0.72, 0.97), menopause status (RR = 0.85; 95% CI:
      0.72, 0.98), education (RR = 0.82; 95% CI: 0.68, 0.96), BMI (RR = 0.85; 95% CI:
      0.70, 1.00) , smoking (RR = 0.83; 95% CI: 0.72, 0.93) and Jadad score of 3 (RR =
      0.76; 95% CI: 0.56, 0.95) and 5 (RR = 0.74; 95% CI: 0.59, 0.89). The Begg's and
      Egger's tests (all P > 0.01) showed no evidence of publication bias. In
      conclusion, our meta-analysis showed an inverse association between tea
      consumption and ovarian cancer risk. High quality cohort-clinical trials should
      be conducted on different tea types and their relationship with ovarian cancer.

PMID- 28445131
TI  - Therapeutic benefit of Salmonella attributed to LPS and TNF-alpha is exhaustible
      and dictated by tumor susceptibility.
AB  - The potential of bacteria-mediated tumor therapy (BMTT) is highlighted by more
      than a century of investigation. Attenuated Salmonella has prevailed as promising
      therapeutic agents. For BMTT - categorized as an immune therapy - the exact
      contribution of particular immune reactions to the therapeutic effect remains
      ambiguous. In addition, one could argue for or against the requirement of
      bacterial viability and tumor targeting. Herein we evaluate the isolated
      therapeutic efficacy of purified LPS and TNF-alpha, which together account for a
      dominant immunogenic pathway of gram negative bacteria like Salmonella. We show
      that therapeutic efficacy against CT26 tumors does not require bacterial
      viability. Analogous to viable Salmonella SL7207, tumor regression by a specific
      CD8+ T cell response can be induced by purified LPS or recombinant TNF-alpha
      (rTNF-alpha). Conversely, therapeutic effects against RenCa tumors were abrogated
      upon bacterial avitalization and limited using isolated adjuvants. This argues
      for an alternative mechanistic explanation for SL7207 against RenCa that depends
      on viability and persistence. Unable to boost bacterial therapies by co-injection
      of rTNF-alpha suggested therapeutic effects along this axis are exhausted by the
      intrinsic adjuvanticity of bacteria alone. However, the importance of TNF-alpha
      for BMTT was highlighted by its support of tumor invasion and colonization in
      concert with lower infective doses of Salmonella. In consideration, bacterial
      therapeutic effectiveness along the axis of LPS and TNF-alpha appears limited,
      and does not offer the necessary plasticity for different tumors. This emphasizes
      a need for recombinant strengthening and vehicular exploitation to accommodate
      potency, plasticity and distinctiveness in BMTT.

PMID- 28445132
TI  - Targeting autophagic cancer stem-cells to reverse chemoresistance in human triple
      negative breast cancer.
AB  - There is growing evidence for the role of cancer stem-cells in drug resistance,
      but with few in situ studies on human tumor samples to decipher the mechanisms by
      which they resist anticancer agents.Triple negative breast cancer (TNBC) is the
      most severe sub-type of breast cancer, occurring in younger women and associated
      with poor prognosis even when treated at a localized stage.We investigated here
      the relationship between complete pathological response after chemotherapy and
      breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women
      with triple negative breast carcinoma (TNBC).We found that chemoresistance was
      associated with large numbers of breast cancer stem-cells, and that these cancer
      stem-cells were neither proliferative nor apoptotic, but in an autophagic state
      related to hypoxia. Using relevant pharmacological models of patient-derived TNBC
      xenografts, we further investigated the role of autophagy in chemoresistance of
      breast cancer stem-cells. We demonstrated that hypoxia increased drug resistance
      of autophagic TNBC stem-cells, and showed that molecular or chemical inhibition
      of autophagic pathway was able to reverse chemoresistance.Our results support
      breast cancer stem-cell evaluation in pre-treatment biopsies of TNBC patients,
      and the need for further research on autophagy inhibition to reverse resistance
      to chemotherapy.

PMID- 28445133
TI  - Baicalein decreases uric acid and prevents hyperuricemic nephropathy in mice.
AB  - Baicalein, a natural flavonoid, is structurally advantageous for binding to
      xanthine oxidoreductase. In our study, molecular docking analysis and Surface
      Plasmon Resonance revealed a direct interaction between baicalein and xanthine
      oxidoreductase. Moreover, 50 mg/kg/d baicalein treatment significantly suppressed
      the viability of xanthine oxidoreductase in hyperuricemia mouse model. The data
      showed that baicalein remarkably prevented renal dysfunction, ameliorated kidney
      fibrosis, alleviated epithelial-mesenchymal transition and oxidative stress in
      hyperuricemia mice. Thus, we concluded that baicalein executed a kidney
      protection action in hyperuricemia and therefore may be used as a therapeutic
      alternative for hyperuricemic nephropathy.

PMID- 28445134
TI  - Novel recombinant immunotoxin of EGFR specific nanobody fused with cucurmosin,
      construction and antitumor efficiency in vitro.
AB  - Epidermal growth factor receptor (EGFR) overexpression is related to the
      increased aggressiveness, metastases, and poor prognosis in various cancers. In
      this study, we successfully constructed a new EGFR nanobody-based immunotoxin
      rE/CUS containing cucurmosin (CUS), The immunotoxin was expressed by prokaryotic
      system and we obtained a yield of 5 mg protein per liter expression medium. The
      percentage of it's binding ability totumor cell lines A549, HepG2, SW116, which
      highly expressed EGFR was 55.6%, 79.6% and 97.1%, respectively, but SW620 was
      only 4.45%. rE/CUS has the ability to bind A549, HepG2, SW116 cells specifically,
      and the antigen binding capability was not affected because of extra part of CUS
      component. The rE/CUS significantly inhibited the cell viability against EGFR
      over expression tumor cell lines in a dose-and time-dependent manner. Moreover,
      rE/CUS also induced apoptosis of HepG2 and A549 mightily. Our results demonstrate
      that rE/CUS is a potential therapeutic strategy for treating EGFR-positive solid
      tumors.

PMID- 28445136
TI  - Selective eradication of cancer cells by delivery of adenovirus-based toxins.
AB  - BACKGROUND AND OBJECTIVE: KRAS mutation is an early event in colorectal cancer
      carcinogenesis. We previously reported that a recombinant adenovirus, carrying a
      pro-apoptotic gene (PUMA) under the regulation of Ets/AP1 (RAS-responsive
      elements) suppressed the growth of cancer cells harboring hyperactive KRAS. We
      propose to exploit the hyperactive RAS pathway, rather than to inhibit it as was
      previously tried and failed repeatedly. We aim to improve efficacy by
      substituting PUMA with a more potent toxin, the bacterial MazF-MazE toxin
      antitoxin system, under a very tight regulation. RESULTS: A massive cell death,
      in a dose-dependent manner, reaching 73% at MOI 10 was seen in KRAS cells as
      compared to 22% in WT cells. Increase expression of MazE (the anti-toxin)
      protected normal cells from any possible internal or external leakage of the
      system and confirmed the selectivity, specificity and safety of the targeting
      system. Considerable tumor shrinkage (61%) was demonstrated in vivo following
      MazEF-encoding adenovirus treatment without any side effects. DESIGN: Efficient
      vectors for cancer-directed gene delivery were constructed; "pAdEasy-Py4-SV40mP
      mCherry-MazF""pAdEasy-Py4-SV40mP-mCherry-MazF-IRES-TetR-CMVmp-MazE-IRES
      EGFP","pAdEasy-DeltaPy4-SV40mP-mCherry-MazF-IRES-TetR-CMVmp-MazE-IRES-EGFP "and
      "pAdEasy-mCherry". Virus particles were produced and their potency was tested.
      Cell death was measured qualitatively by using the fluorescent microscopy and
      colony formation assay, and was quantified by MTT. FACS analysis using annexin V
      and RedDot2 dyes was performed for measuring apoptotic and dead cells,
      respectively. In vivo tumor formation was measured in a xenograft model.
      CONCLUSIONS: A proof of concept for a novel cancer safe and effective gene
      therapy exploiting an aberrant hyperactive pathway is achievable.

PMID- 28445135
TI  - Micrornas in prostate cancer: an overview.
AB  - Prostate cancer is the second highest cause of cancer mortality after lung
      tumours. In USA it affects about 2.8 million men and the incidence increases with
      age in many countries. Therefore, early diagnosis is a very important step for
      patient clinical evaluation and for a selective and efficient therapy. The study
      of miRNAs' functions and molecular mechanisms has brought new knowledge in
      biological processes of cancer. In prostate cancer there is a deregulation of
      several miRNAs that may function as tumour suppressors or oncogenes. The aim of
      this review is to analyze the progress made to our understanding of the role of
      miRNA dysregulation in prostate cancer tumourigenesis.

PMID- 28445137
TI  - Monitoring of KRAS-mutated ctDNA to discriminate pseudo-progression from true
      progression during anti-PD-1 treatment of lung adenocarcinoma.
AB  - OBJECTIVES: Pseudo-progression is a rare but worrying situation for both
      clinicians and patients during immunotherapy. Dedicated ir-RECIST criteria have
      been established to improve this situation. However, this can be sometimes
      considered inadequate and patients experiencing true progression may then receive
      inefficient treatments. Additional reliable tools to discriminate pseudo from
      true progression are thus needed. So far, no biomarker has been identified to
      distinguish pseudo from true progression. We hypothesize that biomarkers
      associated with the molecular characteristics of the tumor may be of interest. To
      avoid a tumor re-biopsy, circulating markers appear to be a less invasive and
      reproducible procedure. As ctDNA kinetics correlate with the response to
      treatment in KRAS-mutated adenocarcinoma, we anticipated that this analysis could
      be of interest. MATERIALS AND METHODS: We monitored the level of KRAS-mutated
      ctDNA by digital droplet PCR in serial plasma samples from two patients who had
      experienced pseudo-progression and compared the variations with those from of a
      patient that had true progression. RESULTS: ctDNA showed rapid and dramatic
      decreases in pseudo-progressive patients, whereas it was strongly increased in
      the progressive patient. CONCLUSIONS: ddPCR of ctDNA may thus be an additional
      tool to discriminate pseudo-progression from true progression for tumors that
      harbor an oncogenic addiction.

PMID- 28445138
TI  - Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the
      cell growth of Langerhans cell histiocytosis.
AB  - Killer cell immunoglobulin-like receptor (KIR) 2DL4 (CD158d) is a receptor for
      human leukocyte antigen-G. The function of KIR2DL4 has been reported in human
      natural killer cell lymphoma and mastocytosis, but not in Langerhans cell
      histiocytosis (LCH). Herein, we examined the expression and function of KIR2DL4
      in LCHs. In pathological specimens, 27 of 36 LCH cases (75.0%) were
      immunohistochemically positive for KIR2DL4. Its expression was independent of
      age, gender, location, multi- or single-system, and the status of BRAFV600E
      immunostaining. We also confirmed the expression of KIR2DL4 mRNA and protein in
      the human LCH-like cell lines ELD-1 and PRU-1. KIR2DL4 protein was distributed in
      the membrane and cytoplasm of ELD-1 cells, but only in the cytoplasm of PRU-1
      cells. An agonistic antibody against KIR2DL4 reduced phosphorylation of
      extracellular signal-regulated kinases (ERKs) and suppressed the cell growth of
      ELD-1 cells in a Src homology region 2 domain-containing phosphatase-2 dependent
      manner, but it had no effect in PRU-1 cells. These results suggest that KIR2DL4
      mediated ERK suppression is a possible therapeutic target for LCH cells.

PMID- 28445139
TI  - Pannexin1 knockout and blockade reduces ischemic stroke injury in female, but not
      in male mice.
AB  - The membrane channel Pannexin 1 (Panx1) mediates apoptotic and inflammatory
      signaling cascades in injured neurons, responses previously shown to be sexually
      dimorphic under ischemic conditions. We tested the hypothesis that Panx1 plays an
      underlying role in mediating sex differences in stroke outcome responses. Middle
      aged, 8-9 month old male and female wild type and Panx1 KO mice were subjected to
      permanent middle cerebral artery (MCA) occlusion, and infarct size and astrocyte
      and microglia activation were assessed 4 days later. The sexually dimorphic
      nature of Panx1 deletion was also explored by testing the effect of probenecid a
      known Panx1 blocker to alter stroke volume. Panx1 KO females displayed
      significantly smaller infarct volumes (~ 50 % reduction) compared to their wild
      type counterparts, whereas no such KO effect occurred in males. This sex-specific
      effect of Panx1 KO was recapitulated by significant reductions in peri-infarct
      inflammation and astrocyte reactivity, as well as smaller infarct volumes in
      probenecid treated females, but not males. Finally, females showed overall,
      higher Panx1 protein levels than males under ischemic conditions. These findings
      unmask a deleterious role for Panx1 in response to permanent MCA occlusion, that
      is unique to females, and provide several new frameworks for understanding sex
      differences in stroke outcome.

PMID- 28445140
TI  - Triple negative breast cancer: the kiss of death.
AB  - One of the most controversial women malignancies, triple negative breast cancers
      (TNBCs) are critically overviewed here, being focused on data useful in clinical
      practice or to improve the therapy and patients survival. TNBCs "choose" young
      women and its "kiss" is, unfortunately deadly in most cases. Currently, few
      sparse data are available in literature concerning the origins of TNBC.
      Vasculogenic mimicry detected in TNBCs, seems to be determined by a population of
      CD133+ cells and may be stimulated by different pharmacological agents such
      sunitinib. Despite the fact that TNBCs do not usually metastasize through the
      lymphatic pathways, TNBCs may be characterized by lymphatic invasion and by an
      increased lymphatic microvascular density. If TNBCs treatment depends on the
      molecular profile of the tumor, the same statement may be postulated for TNBCs
      metastasis. Whether metastases have a similar phenotype as the primary tumor
      remains an enigma. Therefore, the question: 'Could TNBC be subject to a
      standardized, unanimously accepted therapeutic strategy or is it strictly
      subclass-dependent?' remains to be further investigated.

PMID- 28445141
TI  - Downregulation of protein kinase CK2 activity induces age-related biomarkers in
      C. elegans.
AB  - Studies show that a decrease in protein kinase CK2 (CK2) activity is associated
      with cellular senescence. However, the role of CK2 in organism aging is still
      poorly understood. Here, we investigated whether protein kinase CK2 (CK2)
      modulated longevity in Caenorhabditis elegans. CK2 activity decreased with
      advancing age in the worms. Knockdown of kin-10 (the ortholog of CK2beta) led to
      a short lifespan phenotype and induced age-related biomarkers, including
      retardation of locomotion, decreased pharyngeal pumping rate, increased
      lipofuscin accumulation, and reduced resistance to heat and oxidative stress. The
      long lifespan of age-1 and akt-1 mutants was significantly suppressed by kin-10
      RNAi, suggesting that CK2 acts downstream of AGE-1 and AKT-1. Kin-10 knockdown
      did not further shorten the short lifespan of daf-16 mutant worms but either
      decreased or increased the transcriptional activity of DAF-16 depending on the
      promoters of the target genes, indicating that CK2 is an upstream regulator of
      DAF-16 in C. elegans. Kin-10 knockdown increased production of reactive oxygen
      species (ROS) in the worms. Finally, the ROS scavenger N-acetyl-L-cysteine
      significantly counteracts the lifespan shortening and lipofuscin accumulation
      induced by kin-10 knockdown. Therefore, the present results suggest that age
      dependent CK2 downregulation reduces longevity by associating with both ROS
      generation and the AGE-1-AKT-1-DAF-16 pathway in C. elegans.

PMID- 28445142
TI  - Potential biomarkers of DNA replication stress in cancer.
AB  - Oncogene activation is an established driver of tumorigenesis. An apparently
      inevitable consequence of oncogene activation is the generation of DNA
      replication stress (RS), a feature common to most cancer cells. RS, in turn, is a
      causal factor in the development of chromosome instability (CIN), a near
      universal feature of solid tumors. It is likely that CIN and RS are mutually
      reinforcing drivers that not only accelerate tumorigenesis, but also permit
      cancer cells to adapt to diverse and hostile environments. This article reviews
      the genetic changes present in cancer cells that influence oncogene-induced RS
      and CIN, with a particular emphasis on regions of the human genome that show
      enhanced sensitivity to the destabilizing effects of RS, such as common fragile
      sites. Because RS exists in a wide range of cancer types, we propose that the
      proteins involved counteracting this stress are potential biomarkers for
      indicating the degree of RS in cancer specimens. To test this hypothesis, we
      conducted a pilot study to validate whether some of proteins that are known from
      in vitro studies to play an essential role in the RS pathway could be suitable as
      a biomarker. Our results indicated that this is possible. With this review and
      pilot study, we aim to accelerate the development of a biomarker for analysis of
      RS in tumor biopsy specimens, which could ultimately help to stratify patients
      for different forms of therapy such as the RS inhibitors already undergoing
      clinical trials.

PMID- 28445143
TI  - The IGH locus relocalizes to a "recombination compartment" in the perinucleolar
      region of differentiating B-lymphocytes.
AB  - The immunoglobulin heavy chain (IGH) gene loci are subject to specific
      recombination events during B-cell differentiation including somatic
      hypermutation and class switch recombination which mark the end of immunoglobulin
      gene maturation in germinal centers of secondary lymph nodes. These two events
      rely on the activity of activation-induced cytidine deaminase (AID) which
      requires DNA double strand breaks be created, a potential danger to the cell.
      Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence
      staining to a previously described experimental system recapitulating normal B
      cell differentiation ex vivo, we have kinetically analyzed the radial positioning
      of the two IGH gene loci as well as their proximity with the nucleolus,
      heterochromatin and gammaH2AX foci. Our observations are consistent with the
      proposal that these IGH gene rearrangements take place in a specific
      perinucleolar "recombination compartment" where AID could be sequestered thus
      limiting the extent of its potentially deleterious off-target effects.

PMID- 28445144
TI  - Stroma-derived HGF drives metabolic adaptation of colorectal cancer to
      angiogenesis inhibitors.
AB  - The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to
      angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF
      fails to fully activate human MET. To uncover it, we compared the efficacy of AIs
      in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal
      tumors. Species-specific HGF/MET signaling dramatically impaired the response to
      anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays
      mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells
      were completely resistant to hypoxia but extremely sensitive to nutrient
      deprivation. Starvation-induced apoptosis could be prevented by HGF, which
      promoted GLUT1-mediated glucose uptake, sustained glycolysis and activated
      autophagy. Pharmacological inhibition of GLUT1 in the presence of glucose killed
      tumor cells as effectively as glucose deprivation, and this effect was
      antagonized by HGF. Concomitant targeting of GLUT1 and HGF potently suppressed
      growth and dissemination of AI-resistant human tumors in human HGF knock-in SCID
      mice without exacerbating tumor hypoxia. These data suggest that stroma-derived
      HGF protects CRC cells against glucose starvation-induced apoptosis, promoting
      resistance to both AIs and anti-glycolytic agents. Combined inhibition of glucose
      metabolism and HGF/MET signaling ('anti-METabolic therapy') may represent a more
      effective CRC treatment compared to utterly blocking tumor blood supply.

PMID- 28445145
TI  - Influence of serum cholesterol level and statin treatment on prostate cancer
      aggressiveness.
AB  - Both cholesterol levels and the use of statins have been described to influence
      the development and prognosis of prostate cancer (PC). In this retrospective,
      cross-sectional analysis of consecutive cases from a tertiary referral center we
      evaluated an association between hypercholesterolemia (>=5.0mmol/l), the use of
      statins, and advanced/aggressive PC in 767 men with histologically confirmed,
      clinically localized PC awaiting radical prostatectomy. We found that patients
      with HCE (n=287, 37.4%) had a significantly higher incidence of poorly
      differentiated PC (Gleason score >=7b, 81.1% vs. 4.9%), advanced local tumor
      stage (>=pT3, 57.7% vs. 22.2%), and nodal involvement (19.8% vs. 1.6%).
      Multivariate logistic regression analysis identified hypercholesterolemia as a
      risk factor for aggressive and/or advanced PC (OR 2.01, p<0.001) whereas statin
      intake showed an odds ratio of 0.49 (p=0.005) indicating a negative association
      with high-risk PC. Despite a limited number of patients using statins (~9.5%),
      adjusted and weighed multivariate logistic regression models revealed that
      preoperative hypercholesterolemia is associated with a diagnosis of high-risk PC
      which is negatively influenced by statin intake.

PMID- 28445146
TI  - Autophagy and mitophagy in the context of doxorubicin-induced cardiotoxicity.
AB  - Doxorubicin (Dox) is a cytotoxic drug widely incorporated in various chemotherapy
      protocols. Severe side effects such as cardiotoxicity, however, limit Dox
      application. Mechanisms by which Dox promotes cardiac damage and cardiomyocyte
      cell death have been investigated extensively, but a definitive picture has yet
      to emerge. Autophagy, regarded generally as a protective mechanism that maintains
      cell viability by recycling unwanted and damaged cellular constituents, is
      nevertheless subject to dysregulation having detrimental effects for the cell.
      Autophagic cell death has been described, and has been proposed to contribute to
      Dox-cardiotoxicity. Additionally, mitophagy, autophagic removal of damaged
      mitochondria, is affected by Dox in a manner contributing to toxicity. Here we
      will review Dox-induced cardiotoxicity and cell death in the broad context of the
      autophagy and mitophagy processes.

PMID- 28445147
TI  - Identification of rs7350481 at chromosome 11q23.3 as a novel susceptibility locus
      for metabolic syndrome in Japanese individuals by an exome-wide association
      study.
AB  - We have performed exome-wide association studies to identify genetic variants
      that influence body mass index or confer susceptibility to obesity or metabolic
      syndrome in Japanese. The exome-wide association study for body mass index
      included 12,890 subjects, and those for obesity and metabolic syndrome included
      12,968 subjects (3954 individuals with obesity, 9014 controls) and 6817 subjects
      (3998 individuals with MetS, 2819 controls), respectively. Exome-wide association
      studies were performed with Illumina HumanExome-12 DNA Analysis BeadChip or
      Infinium Exome-24 BeadChip arrays. The relation of genotypes of single nucleotide
      polymorphisms to body mass index was examined by linear regression analysis, and
      that of allele frequencies of single nucleotide polymorphisms to obesity or
      metabolic syndrome was evaluated with Fisher's exact test. The exome-wide
      association studies identified six, 11, and 40 single nucleotide polymorphisms as
      being significantly associated with body mass index, obesity (P <1.21 * 10-6), or
      metabolic syndrome (P <1.20 * 10-6), respectively. Subsequent multivariable
      logistic regression analysis with adjustment for age and sex revealed that three
      and five single nucleotide polymorphisms were related (P < 0.05) to obesity or
      metabolic syndrome, respectively, with one of these latter polymorphisms
      rs7350481 (C/T) at chromosome 11q23.3-also being significantly (P < 3.13 * 10-4)
      associated with metabolic syndrome. The polymorphism rs7350481 may thus be a
      novel susceptibility locus for metabolic syndrome in Japanese. In addition,
      single nucleotide polymorphisms in three genes (CROT, TSC1, RIN3) and at four
      loci (ANKK1, ZNF804B, CSRNP3, 17p11.2) were implicated as candidate determinants
      of obesity and metabolic syndrome, respectively.

PMID- 28445149
TI  - Elevated CD147 expression is associated with shorter overall survival in non
      small cell lung cancer.
AB  - A number of studies have reported on the prognostic role of CD147 expression in
      non-small cell lung cancer (NSCLC); however, the results remain controversial.
      This study aims to investigate the impact of CD147 on the prognosis of NSCLC by
      means of a meta-analysis. A literature search was performed for relevant studies
      published before October 29, 2016. The hazard ratios (HRs), odds ratios (ORs),
      and 95% confidence intervals (CIs) were calculated as effective measures.
      Sensitivity analysis and publication bias examination were also conducted. Ten
      eligible studies with a total of 1605 patients were included in this meta
      analysis. CD147 overexpression was correlated with poor overall survival (OS)
      (HR=1.59, 95% CI=1.32-1.91, p<0.001). Elevated CD147 expression was associated
      with the presence of lymph node metastasis (OR=2.31, 95% CI=1.74-3.07, p<0.001)
      and advanced TNM stage (OR=3.03, 95% CI=1.24-7.39, p=0.015). However, no
      significant association between CD147 and sex, age, differentiation, or histology
      was found. No evidence of significant publication bias was identified. This meta
      analysis revealed that overexpression of CD147 was associated with shorter OS,
      the presence of lymph node metastasis and advanced TNM stage in NSCLC. Therefore,
      CD147 could serve as a potential prognostic marker for NSCLC.

PMID- 28445148
TI  - PKC and CaMK-II inhibitions coordinately rescue ischemia-induced GABAergic neuron
      dysfunction.
AB  - Cerebral ischemia leads to neuronal death for stroke, in which the imbalance
      between glutamatergic neurons and GABAergic neurons toward neural excitotoxicity
      is presumably involved. GABAergic neurons are vulnerable to pathological factors
      and impaired in an early stage of ischemia. The rescue of GABAergic neurons is
      expected to be the strategy to reserve ischemic neuronal impairment. As protein
      kinase C (PKC) and calmodulin-dependent protein kinase II (CaMK-II) are activated
      during ischemia, we have investigated whether the inhibitions of these kinases
      rescue the ischemic impairment of cortical GABAergic neurons. The functions of
      GABAergic neurons were analyzed by whole-cell recording in the cortical slices
      during ischemia and in presence of 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L
      tyrosyl]-4-phenylpiperazine (CaMK-II inhibitor) and chelerythrine chloride (PKC
      inhibitor). Our results indicate that PKC inhibitor or CaMK-II inhibitor
      partially prevents ischemia-induced functional deficits of cortical GABAergic
      neurons. Moreover, the combination of PKC and CaMK-II inhibitors synergistically
      reverses this ischemia-induced deficit of GABAergic neurons. One of potential
      therapeutic strategies for ischemic stroke may be to rescue the ischemia-induced
      deficit of cortical GABAergic neurons by inhibiting PKC and CaMK-II.

PMID- 28445150
TI  - Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro
      invasive miR-5096 in glioblastoma cells.
AB  - Inwardly rectifying potassium channels (Kir), and especially the barium-sensitive
      Kir4.1 encoded by KCNJ10, are key regulators of glial functions. A lower
      expression or mislocation of Kir4.1 is detected in human brain tumors. MicroRNAs
      participate in the regulation of ionic channels and associated neurologic
      disorders. Here, we analyze effects of miR-5096 on the Kir4.1 expression and
      function in two glioblastoma cell lines, U87 and U251. Using whole-cell patch
      clamp and western-blot analysis, we show that cell loading with miR-5096
      decreases the Kir4.1 protein level and associated K+ current. Cell treatment with
      barium, a Kir4.1 blocker, or cell loading of miR-5096 both increase the outgrowth
      of filopodia in glioma cells, as observed by time-lapse microscopy. Knocking-down
      Kir4.1 expression by siRNA transfection similarly increased both filopodia
      formation and invasiveness of glioma cells as observed in Boyden chamber assay.
      MiR-5096 also promotes the release of extracellular vesicles by which it
      increases its own transfer to surrounding cells, in a Kir4.1-dependent manner in
      U251 but not in U87. Altogether, our results validate Kir4.1 as a miR-5096 target
      to promote invasion of glioblastoma cells. Our data highlight the complexity of
      microRNA effects and the role of K+ channels in cancer.

PMID- 28445151
TI  - Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular
      carcinoma is AKT-BCL-2 dependent.
AB  - The efficacious treatment of hepatocellular carcinoma (HCC) remains a challenge,
      partially being attributed to intrinsic chemoresistance. Previous reports have
      observed increased TFF3 expression in HCC. Herein, we investigated the functional
      role of TFF3 in progression of HCC, and in both intrinsic and acquired
      chemoresistance. TFF3 expression was observed to be upregulated in HCC and
      associated with poor clinicopathological features and worse patient survival
      outcome. Functionally, forced expression of TFF3 in HCC cell lines increased cell
      proliferation, cell survival, anchorage-independent and 3D matrigel growth, cell
      invasion and migration, and in vivo tumor growth. In contrast, depleted
      expression of TFF3 decreased the oncogenicity of HCC cells as indicated by the
      above parameters. Furthermore, forced expression of TFF3 decreased doxorubicin
      sensitivity of HCC cells, which was attributed to increased doxorubicin efflux
      and cancer stem cell-like behavior of Hep3B cells. In contrast, depletion of TFF3
      increased doxorubicin sensitivity and decreased cancer stem cell-like behavior of
      Hep3B cells. Correspondingly, TFF3 expression was markedly increased in Hep3B
      cells with acquired doxorubicin resistance, while the depletion of TFF3 resulted
      in re-sensitization of the Hep3B cells to doxorubicin. The increased doxorubicin
      efflux and enhanced cancer stem cell-like behavior of the doxorubicin-resistant
      Hep3B cells was observed to be dependent on TFF3 expression. In addition, we
      determined that TFF3-stimulated oncogenicity and chemoresistance in HCC cells was
      mediated by AKT-dependent expression of BCL-2. Hence, therapeutic inhibition of
      TFF3 should be considered to hinder HCC progression and overcome intrinsic and
      acquired chemoresistance in HCC.

PMID- 28445152
TI  - Multiplexed gene expression profiling identifies the FGFR4 pathway as a novel
      biomarker in intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an
      essential regulatory component of bile acid synthesis, and its relationship with
      hepatocellular carcinoma (HCC) has been reported. We investigated the gene
      expression and clinical significance of FGFR4 and related pathways in
      intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years
      (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B
      virus infection, with or without liver cirrhosis. Overall survival was
      significantly associated with FGFR4 (p = 0.004), FGF19 (p = 0.047), FGF21 (p =
      0.04), and KLB (p = 0.03) expression. In the multivariate analysis with potential
      prognostic factors, high expression of FGF19, FGF21, and FGFR4 was significantly
      associated with better survival. In the analysis using the TCGA iCCA dataset,
      mRNA overexpression of at least 1 of the FGFR4-related genes was significantly
      associated with better disease-free survival (p = 0.02). MATERIALS AND METHODS:
      We assessed the expression of 98 genes in formalin-fixed paraffin embedded tumor
      tissue specimens from 46 patients with surgically resected iCCA using a
      NanoString platform. This included 10 FGF pathway genes (e.g. FGFR1-4, KLB, FGF3,
      4, 19, 21, and 23), 19 distal marker genes (e.g. CYP7A1 and CYP17A1), 31 genes
      relevant to HCC and iCCA (e.g. AFP, TS), 18 copy number variation matched genes,
      and 20 control genes. Log-transformation of gene expression was performed for
      normalization and statistical analysis. Overall survival was correlated with gene
      expression (< median vs. >= median) using a log-rank test. The prognostic impact
      of FGFR4-related genes was validated using the public TCGA dataset for iCCA.
      CONCLUSIONS: Our results indicate that mRNA expression of FGFR4-related genes may
      be a biomarker to define the distinctive molecular phenotype of iCCA. Future
      preclinical and clinical validation is required to define the role of the FGFR4
      pathway in iCCA.

PMID- 28445153
TI  - Increased risk of brain metastases in women with breast cancer and p16 expression
      in metastatic lymph-nodes.
AB  - PURPOSE: Metastatic breast cancer is a leading cause of mortality in women,
      partly on account of brain metastases. However, the mechanisms by which cancer
      cells cross the blood-brain barrier remain undeciphered. Most molecular studies
      predicting metastatic risk have been performed on primary breast cancer samples.
      Here we studied metastatic lymph-nodes from patients with breast cancers to
      identify markers associated with the occurrence of brain metastases. RESULTS:
      Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated
      with brain metastases. MATERIALS AND METHODS: Fifty-two patients with HER2
      overexpressing or triple-negative breast carcinoma with lymph nodes and distant
      metastases were included in this study. Transcriptomic analyses were performed on
      laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised
      analyses compared the transcriptomic profiles of women who developed brain
      metastases and those who did not. As a validation series, we studied metastatic
      lymph-nodes from 24 other patients.Immunohistochemistry investigations showed
      that p16 mean scores were significantly higher in patients with brain metastases
      than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was
      confirmed on the validation series. Multivariate analyses showed that the p16
      score was the only variable positively associated with the risk of brain
      metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox
      model, overall survival was shorter in women with a p16 score over 5 in both
      series. CONCLUSIONS: The risk of brain metastases in women with HER2
      overexpressing or triple-negative breast cancer could be better assessed by
      studying p16 protein expression on surgically removed axillary lymph-nodes.

PMID- 28445154
TI  - Role of Delta-like 4 in Jagged1-induced tumour angiogenesis and tumour growth.
AB  - Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key Notch ligands implicated in
      tumour angiogenesis. They were shown to have opposite effects on mouse retinal
      and adult regenerative angiogenesis. In tumours, both ligands are upregulated but
      their relative effects and interactions in tumour biology, particularly in tumour
      response to therapeutic intervention are unclear. Here we demonstrate that DLL4
      and JAG1 displayed equal potency in stimulating Notch target genes in HMEC-1
      endothelial cells but had opposing effects on sprouting angiogenesis in vitro.
      Mouse DLL4 or JAG1 expressed in glioblastoma cells decreased tumour cell
      proliferation in vitro but promoted tumour growth in vivo. mDLL4-expressing
      tumours showed fewer but larger vessels whereas mJAG1-tumours produced more
      vessels. In both tumour types pericyte coverage was decreased but the vessels
      were more perfused. Both ligands increased tumour resistance towards anti-VEGF
      therapy but the resistance was higher in mDLL4-tumours versus mJAG1-tumours.
      However, their sensitivity to the therapy was restored by blocking Notch
      signalling with dibenzazepine. Importantly, anti-DLL4 antibody blocked the effect
      of JAG1 on tumour growth and increased vessel branching in vivo. The mechanism
      behind the differential responsiveness was due to a positive feedback loop for
      DLL4-Notch signalling, rendering DLL4 more dominant in activating Notch
      signalling in the tumour microenvironment. We concluded that DLL4 and JAG1
      promote tumour growth by modulating tumour angiogenesis via different mechanisms.
      JAG1 is not antagonistic but utilises DLL4 in tumour angiogenesis. The results
      suggest that anti-JAG1 therapy should be explored in conjunction with anti-DLL4
      treatment in developing anti-Notch therapies in clinics.

PMID- 28445155
TI  - Retinoblastoma cells activate the AKT pathway and are vulnerable to the PI3K/mTOR
      inhibitor NVP-BEZ235.
AB  - Retinoblastoma is a pediatric cancer of the retina most often caused by
      inactivation of the retinoblastoma (RB1) tumor suppressor gene. We previously
      showed that Rb1 loss cooperates with either co-activating the
      phosphatidylinositol 3-kinase (PI3K)/AKT pathway, or co-deleting Pten, to
      initiate retinoblastoma tumors in mice. The objectives of this study were to
      determine if the AKT pathway is activated in human retinoblastomas and the extent
      that anti-PI3K therapy induces apoptosis in retinoblastoma cells, alone or in
      combination with the DNA damaging drugs carboplatin and topotecan. Serial
      sections from human retinoblastoma tissue microarrays containing 27 tumors were
      stained with antibodies specific to p-AKT, Ki-67, forkhead box O1 (p-FOXO1), and
      ribosomal protein S6 (p-S6) using immunohistochemistry and each tumor sample
      scored for intensity. Human retinoblastoma tumors displayed significant
      correlation between p-AKT intensity with highly proliferative tumors (p = 0.008)
      that were also highly positive for p-FOXO1 (p = 0.002). Treatment with BEZ235, a
      dual PI3K/mTOR inhibitor, reduced phosphorylation levels of the AKT targets p
      FOXO and p-S6 and effectively induced apoptosis the Y79 and Weri-1 human
      retinoblastoma cell lines and in vivo in our retinoblastoma mouse model. Long
      term treatment with BEZ235 in vivo using our retinoblastoma-bearing mice induced
      apoptosis but did not significantly extend the lifespan of the mice. We then co
      administered BEZ235 with topotecan and carboplatin chemotherapeutics in vivo,
      which more effectively induced apoptosis of retinoblastoma, but not normal
      retinal cells than either treatment alone. Our study has increased the variety of
      potentially effective targeted treatments that can be considered for human
      retinoblastoma.

PMID- 28445156
TI  - Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic
      fatty liver disease induced by high fat diet in mice.
AB  - The prevalence of non-alcoholic fatty liver disease is increasing rapidly
      worldwide. However, effective strategies for combating high-fat diet (HFD)
      induced obesity, fatty liver and metabolic disorder are still limited, and
      outcomes remain poor. In the present study, we evaluated the combined actions of
      dietary capsaicin and antibiotics on HFD-induced physiological abnormalities in
      mice. C57BL/6 male mice were fed with HFD (60% calories from fat) for 17 weeks,
      and the resultant pathophysiological effects were examined. Antibiotic treatment
      markedly attenuated gut inflammation and leakiness induced by HFD, whereas
      capsaicin showed limited effects on the gut. However, dietary capsaicin
      significantly increased PPAR-alpha expression in adipose tissue, while
      antibiotics had no such effect. Animals treated with a combination of capsaicin
      and antibiotics had the smallest body weight gain and fat pad index, as well as
      the lowest hepatic fat accumulation. Combination treatment also maximally
      improved insulin responsiveness, as indicated by insulin tolerance tests. These
      results suggest the co-treatment of capsaicin and antibiotics, a novel
      combination strategy, would play synergistically to attenuate the HFD-induced
      obesity, fatty liver and metabolic disorder.

PMID- 28445158
TI  - The HDAC inhibitor valproate induces a bivalent status of the CD20 promoter in
      CLL patients suggesting distinct epigenetic regulation of CD20 expression in CLL
      in vivo.
AB  - Treatment with anti-CD20 antibodies is only moderately efficient in chronic
      lymphocytic leukemia (CLL), a feature which has been explained by the inherently
      low CD20 expression in CLL. It has been shown that CD20 is epigenetically
      regulated and that histone deacetylase inhibitors (HDACis) can increase CD20
      expression in vitro in CLL. To assess whether HDACis can upregulate CD20 also in
      vivo in CLL, the HDACi valproate was given to three del13q/NOTCH1wt CLL patients
      and CD20 levels were analysed (the PREVAIL study). Valproate treatment resulted
      in expected global activating histone modifications suggesting HDAC inhibitory
      effects. However, although valproate induced expression of CD20 mRNA and protein
      in the del13q/NOTCH1wt I83-E95 CLL cell line, no such effects were observed in
      the patients studied. In contrast to the cell line, in patients valproate
      treatment resulted in transient recruitment of the transcriptional repressor EZH2
      to the CD20 promoter, correlating to an increase of the repressive histone mark
      H3K27me3. This suggests that valproate-mediated induction of CD20 may be hampered
      by EZH2 mediated H3K27me3 in vivo in CLL. Moreover, valproate treatment resulted
      in induction of EZH2 and global H3K27me3 in patient cells, suggesting
      transcriptionally repressive effects of valproate in CLL. Our results suggest new
      in vivo mechanisms of HDACis which may have implications on the design of future
      clinical trials in B-cell malignancies.

PMID- 28445157
TI  - LIM kinases: cofilin and beyond.
AB  - LIM kinases are common downstream effectors of several signalization pathways and
      function as a signaling node that controls cytoskeleton dynamics through the
      phosphorylation of the cofilin family proteins. These last 10 years, several
      reports indicate that the functions of LIM kinases are more extended than
      initially described and, specifically, that LIM kinases also control microtubule
      dynamics, independently of their regulation of actin microfilament. In this
      review we analyze the data supporting these conclusions and the possible
      mechanisms that could be involved in the control of microtubules by LIM kinases.
      The demonstration that LIM kinases also control microtubule dynamics has pointed
      to new therapeutic opportunities. Consistently, several new LIM kinase inhibitors
      have been recently developed. We provide a comprehensive comparison of these
      inhibitors, of their chemical structure, their specificity, their cellular
      effects as well as their effects in animal models of various diseases including
      cancer.

PMID- 28445159
TI  - Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary
      disease: a case report and review of the literature.
AB  - Invasive pulmonary aspergillosis (IPA) is an infection that often occurs in
      immunocompromised patients and has a high mortality rate. In recent years, the
      reported incidence of IPA in the context of chronic obstructive pulmonary disease
      (COPD) has seemingly increased. The combination of factors such as long-term
      corticosteroid use, increasing rate of bacterial exacerbations over time, lung
      immune imbalance, and malnutrition are responsible for the emergence of IPA in
      COPD patients. A diagnosis of IPA in COPD patients is difficult to make, which
      explains the delay in antifungal therapy and the high mortality rate. The purpose
      of this study is to increase the recognition and improve the outcomes associated
      with this situation through the description of our case. In patients in which IPA
      is suspected, comprehensive analysis of their clinical manifestations, imaging,
      microbiology and serological examination results are effective means of
      increasing the rate of reliable diagnosis. If the patient's condition permits, a
      pathological specimen should be obtained as soon as possible.

PMID- 28445160
TI  - Association between MMP2-1306 C/T polymorphism and prostate cancer
      susceptibility: a meta-analysis based on 3906 subjects.
AB  - Numerous investigations have addressed the correlation between MMP2-1306C/T
      polymorphism and prostate cancer (PCa) susceptibility. However, these conclusions
      were controversial. Thus, we conducted this current meta-analysis based on six
      studies from PubMed, Embase, Cochrane Library, China Biology Medicine disc (CBM),
      China National Knowledge Infrastructure (CNKI) up to October 21st, 2016. Odds
      ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the
      strength of the correlations. Additionally, different subgroup analyses and
      publication bias tests were performed. Eventually, six previous investigations
      consisted of 1920 cases and 1986 controls were identified and involved in this
      meta-analysis. Consequently, our evidence indicates a certain association between
      MMP2-1306C/T polymorphism and PCa risk among overall population (T vs C: OR =
      1.12, 95% CI = 1.00-1.24, P = 0.040; TT+CT vs CC: OR = 1.16, 95% CI = 1.02-1.32,
      P = 0.026; respectively), as well as the subgroups of Asian population (T vs C:
      OR=1.48, 95% CI=1.13-1.94, P=0.004; TT+CT vs CC: OR = 1.66, 95% CI = 1.21-2.28, P
      = 0.002; respectively) and PCR-RFLP genotyped method (T vs C: OR = 1.58, 95% CI =
      1.19-2.10, P = 0.001; TT+CT vs CC: OR = 1.71, 95% CI = 1.23-2.38, P = 0.001;
      respectively). However, no association was detected in MMP2-1306C/T polymorphism
      with Gleason grading or pathological stage of PCa. Our study indicates MMP2-1306
      C/T polymorphism might increase PCa risk, particularly for Asian population.
      However, future studies comprising large cohort size from multicenter are
      required to confirm our conclusions.

PMID- 28445163
TI  - Annealing of Au, Ag and Au-Ag alloy nanoparticle arrays on GaAs (100) and (111)B.
AB  - Metal nanoparticles (NPs), in particular gold NPs, are often used in the
      fabrication process of semiconductor nanowires. Besides being able to induce the
      1D crystallization of new material, it is highly beneficial if the NPs can be
      used to dictate the position and diameter of the final nanowire structure. To
      achieve well-defined NP arrays of varying diameter and pitch distances for
      nanowire growth, it is necessary to understand and control the effect that a pre
      growth annealing process may have on the pre-defined NP arrays. Recently, it has
      been demonstrated that silver (Ag) may be an alternative to using gold (Au) NPs
      as seed for particle-seeded nanowire fabrication. This work brings light onto the
      effect of annealing of Au, Ag and Au-Ag alloy metal NP arrays in two commonly
      used epitaxial systems, the molecular beam epitaxy (MBE) and the metalorganic
      vapor phase epitaxy (MOVPE). The metal NP arrays are fabricated with the aid of
      electron beam lithography on GaAs 100 and 111B wafers and the evolution of the
      NPs with respect to shape, size and position on the surfaces is studied after
      annealing using scanning electron microscopy. We find that while the Au NP arrays
      are found to be stable when annealed up to 600  degrees C in a MOVPE system, a
      diameter and pitch dependent splitting of the particles is seen for annealing in
      a MBE system. The Ag NP arrays are found to be less stable, with smaller
      diameters (<=50 nm) dissolving during the annealing process in both epitaxial
      systems. In general, the mobility of the NPs is observed to differ between the
      two the GaAs 100 and 111B surfaces. Finally, our observations on the effect of
      annealing on Au-Ag alloy NP arrays suggest that these NP can withstand necessary
      annealing conditions for a complete de-oxidation of GaAs surfaces in both MOVPE
      and MBE.

PMID- 28445164
TI  - Simple and scalable preparation of master mold for nanoimprint lithography.
AB  - Nanoimprint lithography (NIL) is one of the most prominent bottom-up techniques
      for duplicating nanostructures with a high throughput. However, fabrication of
      starting master mold commonly requires expensive equipment of top-down
      techniques, or additional steps to transfer the fabricated patterns from bottom
      up methods. Here we demonstrate that a SiO2 nanostructure manufactured from a
      self-assembled block copolymer, polystyrene-b-polydimethylsiloxane (PS-b-PDMS),
      directly serves as a master mold for NIL without further modification. A
      hexagonally aligned pattern over the entire substrate is established using a
      simple technique; solvent annealing and etching. Etching also plays an important
      role in endowing fluorine on the surface of SiO2, thus promoting smooth demolding
      upon imprinting. The obtained pattern of the SiO2 nanostructure is transferred to
      a polymer surface using UV nanoimprint. Identical patterns of the SiO2
      nanostructure are elaborately reproduced on Ni and Cu nanodot arrays via
      electroplating on the polymer transcript, which was verified by morphological
      observations. The uniformity of the replicated Ni nanodot array is evaluated
      using spectroscopic ellipsometry. The measured optical response of the Ni nanodot
      is validated by electromagnetically simulated results, indicating that the
      pattern transfer is not limited to a small local area. In addition, the
      durability of the SiO2 mold pattern is corroborated after the imprinting process,
      thus guaranteeing the reusability of the fabricated nanostructure as a master
      mold. The proposed approach does not require any high-end lithographic
      techniques; this may result in significant cost and time reductions in future
      nanofabrication.

PMID- 28445161
TI  - Zerumbone ameliorates high-fat diet-induced adiposity by restoring AMPK-regulated
      lipogenesis and microRNA-146b/SIRT1-mediated adipogenesis.
AB  - Obesity is characterized by increased fat mass, as adipose tissue serves as a
      storage site for excess energy from food consumption. In obesity, altered lipid
      metabolism of adipose tissue, characterized by fatty acid uptake, de novo
      lipogenesis, and lipolysis, are induced. In this study, we examined the effect of
      zerumbone, a major sesquiterpene from wild ginger, on high-fat diet (HF)-induced
      obesity and dysregulated lipid metabolism in the white adipose tissues (WAT) of
      C57BL/6N mice. Dietary supplementation with zerumbone ameliorated HF-induced
      obesity and improved impaired lipid metabolism in WAT. Zerumbone additionally
      induced AMPK activation and phosphorylation of acetyl-CoA carboxylase, and
      effectively decreased adipogenic differentiation, in a concentration-dependent
      manner in the 3T3-L1 cells. Dysregulated microRNAs in obese WAT and adipocytes
      were examined, and zerumbone treatment was found to effectively reverse the
      robust upregulation of microRNA-146b. An increase in the levels of SIRT1, the
      direct target of microRNA-146b, was observed in zerumbone-treated differentiated
      adipocytes. This increase was additionally observed in WAT of zerumbone
      supplemented mice. The antiadipogenic effect of zerumbone was found to be
      abolished in SIRT1-silenced 3T3-L1 cells. The increase in SIRT1 levels induced by
      zerumbone led to deacetylation of FOXO1 and PGC1alpha in WAT and differentiated
      3T3-L1 cells. These findings indicate that zerumbone ameliorated diet-induced
      obesity and inhibited adipogenesis, and that the underlying mechanisms involved
      AMPK and the microRNA-146b/SIRT1 pathway. Zerumbone may represent a potential
      therapeutic candidate for the prevention and treatment of metabolic diseases,
      particularly obesity.

PMID- 28445165
TI  - Non-diverging analytical expression for the sensitivity of converging SPECT
      collimators.
AB  - Accurate analytical expressions for collimator resolution and sensitivity are
      important tools in the optimization of SPECT systems. However, presently known
      expressions for the sensitivity of converging collimators either diverge near the
      focal point or focal line(s), or are only valid on the collimator axis. As a
      result, these expressions are unsuitable to calculate volumetric sensitivity for
      e.g. short-focal length collimators that focus inside the object to enhance
      sensitivity. To also enable collimator optimization for these geometries, we here
      present non-diverging sensitivity formulas for astigmatic, cone beam and fan beam
      collimators that are applicable over the full collimator's field-of-view. The
      sensitivity was calculated by integrating previously derived collimator response
      functions over the full detector surface. Contrary to common approximations, the
      varying solid angle subtended by different detector pixels was fully taken into
      account which results in a closed-form non-diverging formula for the sensitivity.
      We validated these expressions using ray-tracing simulations of a fan beam and an
      astigmatic cone beam collimator and found close agreement between the simulations
      and the sensitivity expression. The largest differences with the simulation were
      found close to the collimator, where sensitivity depends on the exact placement
      of holes and septa, while our expression represents an average over all possible
      placements as is common practice for analytical sensitivity expressions. We
      checked that average differences between the analytical expression and
      simulations reduced to less than 1% of the maximum sensitivity when we averaged
      our simulations over different septa locations. Moreover, we found that our new
      expression reduced to the traditional diverging formula under certain
      assumptions. Therefore, the newly derived sensitivity expression may enable the
      optimization of converging collimators for a wide range of applications, in
      particular when the focus is close to, or in, the object of interest.

PMID- 28445166
TI  - Repurposing compact discs as master molds to fabricate high-performance organic
      nanowire field-effect transistors.
AB  - Organic field-effect transistors (OFETs) have been developed over the past few
      decades due to their potential applications in future electronics such as
      wearable and foldable electronics. As the electrical performance of OFETs has
      improved, patterning organic semiconducting crystals has become a key issue for
      their commercialization. However, conventional soft lithographic techniques have
      required the use of expensive processes to fabricate high-resolution master
      molds. In this study, we demonstrated a cost-effective method to prepare
      nanopatterned master molds for the fabrication of high-performance nanowire
      OFETs. We repurposed commercially available compact discs (CDs) as master molds
      because they already have linear nanopatterns on their surface. Flexible
      nanopatterned templates were replicated from the CDs using UV-imprint
      lithography. Subsequently, 6,13-bis-(triisopropylsilylethynyl) pentacene
      nanowires (NWs) were grown from the templates using a capillary force-assisted
      lithographic technique. The NW-based OFETs showed a high average field-effect
      mobility of 2.04 cm2 V-1 s-1. This result was attributed to the high
      crystallinity of the NWs and to their crystal orientation favorable for charge
      transport.

PMID- 28445167
TI  - Spatial features of dose-surface maps from deformably-registered plans correlate
      with late gastrointestinal complications.
AB  - This study investigates the associations between spatial distribution of dose to
      the rectal surface and observed gastrointestinal toxicities after deformably
      registering each phase of a combined external beam radiotherapy (EBRT)/high-dose
      rate brachytherapy (HDRBT) prostate cancer treatment. The study contains data for
      118 patients where the HDRBT CT was deformably-registered to the EBRT CT. The
      EBRT and registered HDRBT TG43 dose distributions in a reference 2 Gy/fraction
      were 3D-summed. Rectum dose-surface maps (DSMs) were obtained by virtually
      unfolding the rectum surface slice-by-slice. Associations with late peak
      gastrointestinal toxicities were investigated using voxel-wise DSM analysis as
      well as parameterised spatial patterns. The latter were obtained by thresholding
      DSMs from 1-80 Gy (increment  =  1) and extracting inferior-superior extent, left
      right extent, area, perimeter, compactness, circularity and ellipse fit
      parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate
      features with toxicities. Rectal bleeding, stool frequency, diarrhoea and
      urgency/tenesmus were associated with greater lateral and/or longitudinal spread
      of the high doses near the anterior rectal surface. Rectal bleeding and stool
      frequency were also influenced by greater low-intermediate doses to the most
      inferior 20% of the rectum and greater low-intermediate-high doses to 40-80% of
      the rectum length respectively. Greater low-intermediate doses to the superior
      20% and inferior 20% of the rectum length were associated with anorectal pain and
      urgency/tenesmus respectively. Diarrhoea, completeness of evacuation and
      proctitis were also related to greater low doses to the posterior side of the
      rectum. Spatial features for the intermediate-high dose regions such as area,
      perimeter, compactness, circularity, ellipse eccentricity and confinement to
      ellipse fits were strongly associated with toxicities other than anorectal pain.
      Consequently, toxicity is related to the shape of isodoses as well as dose
      coverage. The findings indicate spatial constraints on doses to certain sections
      of the rectum may be important for reducing toxicities and optimising dose.

PMID- 28445168
TI  - Enhanced photoluminescence of corrugated Al2O3 film assisted by colloidal CdSe
      quantum dots.
AB  - We present the enhanced photoluminescence (PL) of a corrugated Al2O3 film enabled
      by colloidal CdSe quantum dots. The colloidal CdSe quantum dots are fabricated
      directly on a corrugated Al2O3 substrate using an electrochemical deposition
      (ECD) method in a microfluidic system. The photoluminescence is excited by using
      a 150 nm diameter ultraviolet laser spot of a scanning near-field optical
      microscope. Owing to the electron transfer from the conduction band of the CdSe
      quantum dots to that of Al2O3, the enhanced photoluminescence effect is observed,
      which results from the increase in the recombination rate of electrons and holes
      on the Al2O3 surface and the reduction in the fluorescence of the CdSe quantum
      dots. A periodically-fluctuating fluorescent spectrum was exhibited because of
      the periodical wire-like corrugated Al2O3 surface serving as an optical grating.
      The spectral topographic map around the fluorescence peak from the Al2O3 areas
      covered with CdSe quantum dots was unique and attributed to the uniform
      deposition of CdSe QDs on the corrugated Al2O3 surface. We believe that the
      microfluidic ECD system and the surface enhanced fluorescence method described in
      this paper have potential applications in forming uniform optoelectronic films of
      colloidal quantum dots with controllable QD spacing and in boosting the
      fluorescent efficiency of weak PL devices.

PMID- 28445169
TI  - Continuous, size and shape-control synthesis of hollow silica nanoparticles
      enabled by a microreactor-assisted rapid mixing process.
AB  - Hollow silica nanoparticles (HSNPs) were synthesized using a microreactor
      assisted system with a hydrodynamic focusing micromixer. Due to the fast mixing
      of each precursor in the system, the poly(acrylic acid) (PAA) thermodynamic
      locked (TML) conformations were protected from their random aggregations by the
      immediately initiated growth of silica shells. When altering the mixing time
      through varying flow rates and flow rate ratios, the different degrees of the
      aggregation of PAA TML conformations were observed. The globular and necklace
      like TML conformations were successfully captured by modifying the PAA
      concentration at the optimized mixing condition. Uniform HSNPs with an average
      diameter ~30 nm were produced from this system. COMSOL numerical models was
      established to investigate the flow and concentration profiles, and their effects
      on the formation of PAA templates. Finally, the quality and utility of these
      uniform HSNPs were demonstrated by the fabrication of antireflective thin films
      on monocrystalline photovoltaic cells which showed a 3.8% increase in power
      conversion efficiency.

PMID- 28445170
TI  - Using an iPad for Basic Communication Between Spanish-Speaking Families and
      Nurses in Pediatric Acute Care: A Feasibility Pilot Study.
AB  - The growing number of Spanish speakers in the United States poses communication
      challenges for healthcare providers. Language barriers in pediatric acute care
      have been associated with an increased risk for adverse events, longer hospital
      stays, and decreased quality of care. In addition, clinicians' usage of
      interpreter services is inconsistent. In fact, nurses often lack interpreter
      support during daily bedside care. Nursing staff at a pediatric children's
      hospital in the southeastern United States identified bedside communication with
      Spanish-speaking patients and families as a clinical challenge. To address this
      challenge, a basic communication interface, UTalk version 1.0 (the author is the
      owner and proprietor), supported by an Apple iPad, was developed by the
      researcher with input from nursing staff, a certified medical interpreter, and
      Spanish-speaking community members. A feasibility pilot study of the interface's
      usability and engagement was conducted on the hospital's pediatric medical
      surgical unit through qualitative interviews with nurse-family dyads. Three
      themes emerged from the data: UTalk-facilitated communication, UTalk needs
      improvement, and interpreter miscommunication. These findings indicate that a
      mobile digital device interface is a feasible method for augmenting bedside
      communication with Spanish-speaking patients and families. These results also may
      serve as a reference for the development of similar mobile device interfaces.
      Further research with a larger sample size is needed.

PMID- 28445171
TI  - Identification of Depressive Signs in Patients and Their Family Members During
      iPad-based Audiovisual Sessions.
AB  - Home parenteral nutrition requires a daily life-sustaining intravenous infusion
      over 12 hours. The daily intravenous infusion home care procedures are stringent,
      time-consuming tasks for patients and family caregivers who often experience
      depression. The purposes of this study were (1) to assess home parenteral
      nutrition patients and caregivers for depression and (2) to assess whether
      depressive signs can be seen during audiovisual discussion sessions using an
      Apple iPad Mini. In a clinical trial (N = 126), a subsample of 21 participants
      (16.7%) had depressive symptoms. Of those with depression, 13 participants were
      home parenteral nutrition patients and eight were family caregivers; ages ranged
      from 20 to 79 years (with 48.9 [standard deviation, 17.37] years); 76.2% were
      female. Individual assessments by the mental health nurse found factors related
      to depressive symptoms across all 21 participants. A different nurse observed
      participants for signs of depression when viewing the videotapes of the
      discussion sessions on audiovisual technology. Conclusions are that depression
      questionnaires, individual assessment, and observation using audiovisual
      technology can identify depressive symptoms. Considering the growing provision of
      healthcare at a distance, via technology, recommendations are to observe and
      assess for known signs and symptoms of depression during all audiovisual
      interactions.

PMID- 28445172
TI  - Telehealth Intensive Care Unit Nurse Surveillance of Sepsis.
AB  - The purpose of this article is to describe the usability and human factors
      engineering standards used in development of a sepsis alert known as the sepsis
      prompt. Sensory processing, cognitive processing, signal detection, criterion
      response, and user satisfaction were evaluated with controlled user testing and
      critical incident response techniques. Nurses reported that the sepsis prompt was
      visible and distinct, making it easily detectable. The prompt provided a clear
      response mechanism and adequately balanced the number of false alerts with the
      likelihood of misses. Designers were able to use a mental model approach as they
      designed the prompt because the nurses were already using a manual sepsis
      detection process. This may have predisposed the nurses to response bias, and as
      such, they were willing to accommodate more false alarms than nurses who are not
      familiar with sepsis screening (surveillance). Nurses not currently screening for
      sepsis may not place the same value on this alert and find it an annoyance. The
      sepsis prompt met usability standards, and the nurses reported that it improved
      efficiency over the manual screening method.

PMID- 28445173
TI  - Hydroa Vacciniforme-Like Lymphoma in Tibetan Children: 2 Cases and a Literature
      Review.
AB  - Hydroa vacciniforme-like lymphoma shows a marked predilection for the pediatric
      population, especially in Latin America and Asia. Here, we present 2 pediatric
      patients from Tibet of China, which is the first report from this area.

PMID- 28445174
TI  - Obstetric Anesthesia for a Pregnant Woman With Brainstem Cavernous Malformations:
      A Case Report.
AB  - There are no well-defined guidelines for obstetric and anesthetic management of
      pregnant patients with cerebral cavernous malformations (CMs). We need to pay
      careful attention to the attendant risks of both general and neuraxial anesthesia
      in this population. Here, we describe the anesthetic management of a pregnant
      woman with brainstem CMs who underwent cesarean delivery. We selected a general
      anesthetic technique because of concerns of undesirable effects of neuraxial
      anesthesia in the presence of cerebral CMs.

PMID- 28445176
TI  - Novel lipid modifying drugs to lower LDL cholesterol.
AB  - PURPOSE OF REVIEW: Statins have long been the cornerstone for the prevention of
      cardiovascular disease (CVD). However, because of perceived adverse effects and
      insufficient efficacy in certain groups of patients, considerable interest exists
      in the search for alternatives to lower LDL-cholesterol (LDL-C), and the recent
      approvals of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
      underlines the success of this quest. Here, we give an updated overview on the
      most recent developments in the area of LDL-C lowering agents. RECENT FINDINGS:
      The clinical effects of the PCSK9 inhibitors are promising, especially now that
      the FOURIER and SPIRE programmes are published. Most cholesterylester-transfer
      protein inhibitors, however, except anacetrapib, have been discontinued because
      of either toxicity or lack of efficacy in large cardiovascular outcome trials.
      Other agents - like mipomersen, lomitapide, ETC-1002, and gemcabene - aim to
      lower LDL-C in different ways than solely through the LDL receptor, opening up
      possibilities for treating patients not responding to conventional therapies. New
      discoveries are also being made at the DNA and RNA level, with mipomersen being
      the first approved therapy based on RNA intervention in the United States for
      homozygous familial hypercholesterolemia. SUMMARY: Recent years have witnessed a
      new beginning for cholesterol-lowering compounds. With increased knowledge of
      lipid metabolism a score of new therapeutic targets has been identified.
      Mechanisms for modulation of those targets are also becoming more diverse while
      statins remain the backbone of CVD prevention, the new alternatives, such as
      PCSK9 monoclonals will probably play an important additional role in treatment of
      patients at risk for CVD.

PMID- 28445177
TI  - Workplace Bullying as a Predictor of Disability Retirement: A Prospective
      Registry Study of Norwegian Employees.
AB  - OBJECTIVE: The aim of this study was to determine 1) whether bullying is related
      to all-cause disability retirement, 2) whether bullying contributes to the
      variance in disability retirement above high job demands and lack of job control,
      and 3) to establish gender differences in the relationship. METHODS: Survey data
      from 14,501 Norwegian employees on exposure factors linked to registry data on
      all-cause disability retirement. RESULTS: Bullying significantly predicted risk
      of disability retirement (hazard ratio = 1.55; 95% confidence interval = 1.13 to
      2.12). This relationship remained statistically significant after adjusting for
      job demands and lack of job control. Women had the highest risk of disability,
      but both bullied men and women had a higher risk of disability than nonbullied
      employees of the same gender. CONCLUSION: Bullying is a risk factor for
      disability retirement. Measures taken to prevent bullying may be beneficial for
      reducing both health problems and disability retirement.

PMID- 28445179
TI  - A Question Worth Asking.

PMID- 28445178
TI  - Familial Hemiplegic Migraine With Asymmetric Encephalopathy Secondary to ATP1A2
      Mutation: A Case Series.
AB  - INTRODUCTION: Familial hemiplegic migraine (FHM) is a genetic disease with a
      variable clinical phenotype. The imaging and electroencephalogram (EEG)
      correlates of FHM are not well described. CASE SERIES: We describe a case series
      of five young women aged 12 to 32 years. Each case presented with headache,
      encephalopathy, and hemiparesis of varying severity. One patient developed
      seizures. All patients improved spontaneously. INVESTIGATIONS: Asymmetric slow
      wave activity was seen on electroencephalogram in each case. One patient
      developed marked unilateral cortical edema on MR imaging. Cerebro-spinal fluid
      (CSF) studies were normal for all patients. Genetic testing in each case showed a
      mutation of the ATP1A2 gene. One of the mutations identified is a novel mutation.
      DISCUSSION: Genetic mutation of the ATP1A2 gene results in a channelopathy which
      is thought to predispose to spreading depolarization, the probable physiologic
      correlate of migraine aura. We hypothesize that widespread prolonged
      depolarization accounts for the characteristic electroencephalogram findings in
      these cases. Familial hemiplegic migraine should be considered in the
      differential diagnosis of an asymmetric encephalopathy, particularly when CSF and
      imaging studies are normal.

PMID- 28445180
TI  - Activation of the CXCR4 chemokine receptor enhances biological functions
      associated with B16 melanoma liver metastasis.
AB  - The CXCR4 chemokine receptor plays an essential role in the homing of cells to
      organs expressing its ligand, CXCL12. CXCR4 expressed on tumor cells might
      regulate their traffic during metastasis. Here, we investigated whether the
      activation of CXCR4 on B16 murine melanoma cells regulates biological functions
      associated with metastasis, in vitro and in vivo. Flow cytometry and PCR analysis
      showed that B16 constitutively expresses high levels of CXCR4 (CXCR4-B16).
      Biological assays showed that the activation of CXCR4, by its ligand CXCL12,
      increases the migration, invasion, and proliferation of CXCR4-B16. AMD3100
      significantly inhibited the stimulatory migrating effect induced by CXCL12.
      Treatment of CXCR4-B16 with CXCL12 increases their adhesion to liver sinusoidal
      endothelial cell (LSEC) monolayers. LSEC, expressing CXCL12, increased the
      migration of CXCR4-B16. In a liver metastasis model, CXCR4-B16 metastasis was
      associated with an increased expression of CXCL12 in LSEC territories. CXCR4-B16
      cells were located close to LSEC microenvironments expressing CXCL12. Increased
      liver metastasis was observed after injecting CXCR4-B16 cells previously treated
      with CXCL12. Our results provide evidence showing that CXCR4 plays an important
      role in regulating biological functions associated with B16 liver metastasis.

PMID- 28445181
TI  - Two Versus One High-Frequency Repetitive Transcranial Magnetic Stimulation
      Session per Day for Treatment-Resistant Depression: A Randomized Sham-Controlled
      Trial. Response to Andrade and Colleagues.

PMID- 28445182
TI  - Electroconvulsive Therapy in Autoimmune and Vascular Pathology.

PMID- 28445183
TI  - Successful Anesthetic Management of Morbidly Obese Patients During
      Electroconvulsive Therapy With the ProSeal Laryngeal Mask Airway in a Head-up
      Position: A Report of 2 Cases.

PMID- 28445184
TI  - Electroconvulsive Therapy in the Treatment of Patient With Depressive Disorder
      After Traumatic Brain Injury, Intracranial Bleeding, and Polytrauma.

PMID- 28445185
TI  - Orbicularis Retaining Ligament Release in Lower Blepharoplasty: Assessing
      Efficacy and Complications.
AB  - PURPOSE: Release of the orbicularis retaining ligament (ORL) has been advocated
      as a technique to address tear trough deformities. This study sought to compare
      the effectiveness and morbidity of lower blepharoplasty with and without ORL
      release. METHODS: Retrospective chart review of 53 lower blepharoplasty patients.
      Twenty-six patients had ORL release and 27 patients did not. Three independent
      masked experienced cosmetic surgeons reviewed preoperative and postoperative
      photographs to assess degree of swelling, ecchymosis, change in steatoblepharon
      and tear trough deformity, and overall aesthetic result. RESULTS: There were no
      significant differences in overall aesthetic result, change in steatoblepharon or
      tear trough deformity, and postoperative ecchymosis in patients who had ORL
      release compared with those who did not. Patients who had ORL release had
      postoperative swelling and chemosis of significantly longer duration and a higher
      likelihood of developing postoperative ectropion. CONCLUSIONS: Orbicularis
      retaining ligament release does not appear to result in additional aesthetic
      benefit in lower blepharoplasty patients and may increase morbidity in the form
      of ectropion and prolonged swelling and chemosis.

PMID- 28445186
TI  - The Hip Fracture Patient on Warfarin: Evaluating Blood Loss and Time to Surgery.
AB  - OBJECTIVES: To compare blood loss, delay of surgery, and short-term adverse
      events in (1) patients admitted on warfarin versus nonanticoagulated controls and
      (2) warfarin patients with day of surgery (DOS) international normalized ratio
      (INR) of 1.5 or greater versus below 1.5. DESIGN: Retrospective cohort. SETTING:
      Academic Level I trauma center. PATIENTS/PARTICIPANTS: One hundred twenty four
      patients treated surgically for hip fractures including patients presenting on
      warfarin (n = 62) and matched controls (n = 62). INTERVENTION: Cephalomedullary
      nailing (CMN), hemiarthroplasty, or total hip arthroplasty. MAIN OUTCOME
      MEASURES: The primary outcome was transfusion rate. Secondary outcomes included
      calculated blood loss, 30-day complication rate, and hours from emergency
      department presentation to surgery. RESULTS: There was no significant difference
      in blood transfusion rates between the warfarin and control groups (P = 0.86).
      Blood transfusion was required in 58.1% of patients in the warfarin group (48.3%
      of arthroplasties and 65.5% of CMNs) compared with 56.6% of controls (41.9% of
      arthroplasties and 73.3% of CMNs). There were also no significant differences in
      calculated blood loss or in complication rates. Patients on warfarin had
      significantly longer time to surgery (P < 0.01). Subanalysis of the warfarin
      group showed that patients with DOS INR at or above 1.5 had similar transfusion
      rates, blood loss, and complications compared with patients with INR below 1.5.
      Treatment with CMN was the only covariate that was found to be a significant
      independent predictor of transfusion on multivariable analysis (P = 0.048).
      CONCLUSIONS: Patients with hip fractures admitted on warfarin seem to be at
      similar risk of transfusion or adverse events compared with nonanticoagulated
      patients. Awaiting normalization of INR delayed surgery without reducing bleeding
      or preventing complications. Within reason, surgeons may consider proceeding with
      surgery in patients with INR above 1.5 if patients are otherwise medically
      optimized. The upper limit above which surgery causes increased blood loss is
      currently unknown. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 28445187
TI  - The effects of inherited NUDT15 polymorphisms on thiopurine active metabolites in
      Japanese children with acute lymphoblastic leukemia.
AB  - Thiopurines [e.g. mercaptopurine (MP)] are widely used as chemotherapeutic agents
      in the treatment of pediatric acute lymphoblastic leukemia with dose-limiting
      hematopoietic toxicity. Recently, germline variants in NUDT15 have been
      identified as a major genetic cause for MP-related bone marrow suppression, and
      there is increasing interest in the clinical implementation of NUDT15 genotype
      guided MP dose individualization. Therefore, we sought to evaluate the effects of
      NUDT15 on thiopurine metabolism and identify pharmacologic markers to inform
      NUDT15 genotype-guided MP dosing. In 55 Japanese children with acute
      lymphoblastic leukemia, we simultaneously measured both thioguanine nucleotides
      (TGN) in red blood cells and DNA-incorporated thioguanine (DNA-TG) in white blood
      cells. TGN levels were significantly lower in patients with NUDT15 deficiency,
      likely because of toxicity-related MP dose reduction. In contrast, when exposed
      to the same dose of MP, DNA-TG accumulated more efficiently in vivo with
      increasing number of risk alleles in NUDT15 (P=4.0*10). Cytosolic TGN and nuclear
      DNA-TG were correlated positively with each other across genotype groups
      (P=6.5*10), but the ratio of DNA-TG to TGN was significantly higher in NUDT15
      deficient patients (P=3.6*10), consistent with excessive MP activation. In
      conclusion, our results suggest that DNA-TG is a more relevant MP metabolite than
      TGN to inform NUDT15 genotype-guided dose adjustments.

PMID- 28445189
TI  - Proton pump inhibitor-responsive esophageal eosinophilia: still a valid
      diagnosis?
AB  - PURPOSE OF REVIEW: To update rapidly evolving concepts regarding the
      controversial entity of 'proton pump inhibitor (PPI)-responsive esophageal
      eosinophilia,' referring to patients with clinical, endoscopic and histologic
      features of eosinophilic esophagitis (EoE) who achieve remission on PPI therapy.
      RECENT FINDINGS: Up to half of pediatric and adult patients with typical EoE
      symptoms and histology achieve clinico-pathologic remission on PPI therapy,
      irrespective of whether esophageal pH monitoring demonstrates abnormal acid
      reflux. In patients with clinical and histologic features of EoE, genotypic and
      phenotypic features of PPI responders and nonresponders are virtually
      indistinguishable, and different from those of patients with gastroesophageal
      reflux disease. In PPI responders, PPIs effects on esophageal Th2 inflammation
      and gene expression are similar to those of topical steroids in PPI
      nonresponders. These therapies, along with diets, recently have been shown to be
      potentially interchangeable in two small series. SUMMARY: Proton pump inhibitor
      responsive esophageal eosinophilia is an inappropriate disease descriptor,
      arbitrarily based on a response to a single drug, and should be abandoned.
      Patients who have esophageal eosinophilia and esophageal symptoms that resolve
      with PPI therapy have phenotypic, molecular, mechanistic, and therapeutic
      features indistinguishable from similar patients who do not respond to PPIs.
      These patients with PPI responsiveness should be considered within the spectrum
      of EoE.

PMID- 28445188
TI  - TPMT, COMT and ACYP2 genetic variants in paediatric cancer patients with
      cisplatin-induced ototoxicity.
AB  - OBJECTIVES: Cisplatin ototoxicity affects 42-88% of treated children. Catechol-O
      methyltransferase (COMT), thiopurine methyltransferase (TPMT) and AYCP2 genetic
      variants have been associated with ototoxicity, but the findings have been
      contradictory. The aims of the study were as follows: (a) to investigate these
      associations in a carefully phenotyped cohort of UK children and (b) to perform a
      systematic review and meta-analysis. METHODS: We recruited 149 children from
      seven UK centres using a retrospective cohort study design. All participants were
      clinically phenotyped carefully. Genotyping was performed for one ACYP2
      (rs1872328), three TPMT (rs12201199, rs1142345 and rs1800460) and two COMT
      (rs4646316 and rs9332377) variants. RESULTS: For CTCAE grading, hearing loss was
      present in 91/120 (75.8%; worst ear) and 79/120 (65.8%; better ear). Using Chang
      grading, hearing loss was diagnosed in 85/119 (71.4%; worst ear) versus 75/119
      (63.0%; better ear). No TPMT or COMT single-nucleotide polymorphisms (SNPs) were
      associated with ototoxicity. ACYP2 SNP rs1872328 was associated with ototoxicity
      (P=0.027; worst ear). Meta-analysis of our data with that reported in previous
      studies showed the pooled odds ratio (OR) to be statistically significant for
      both the COMT SNP rs4646316 (OR: 1.50; 95% confidence interval: 1.15-1.95) and
      the ACYP2 SNP rs1872328 (OR: 5.91; 95% confidence interval: 1.51-23.16).
      CONCLUSION: We showed an association between the ACYP2 polymorphism and cisplatin
      induced ototoxicity, but not with the TPMT and COMT. A meta-analysis was
      statistically significant for both the COMT rs4646316 and the ACYP2 rs1872328
      SNPs. Grading the hearing of children with asymmetric hearing loss requires
      additional clarification.

PMID- 28445190
TI  - Cognitive learning and its future in urology: surgical skills teaching and
      assessment.
AB  - PURPOSE OF REVIEW: The aim of this study is to provide an overview of the current
      status of novel cognitive training approaches in surgery and to investigate the
      potential role of cognitive training in surgical education. RECENT FINDINGS:
      Kinematics of end-effector trajectories, as well as cognitive state features of
      surgeon trainees and mentors have recently been studied as modalities to
      objectively evaluate the expertise level of trainees and to shorten the learning
      process. Virtual reality and haptics also have shown promising in research
      results in improving the surgical learning process by providing feedback to the
      trainee. SUMMARY: 'Cognitive training' is a novel approach to enhance training
      and surgical performance. The utility of cognitive training in improving motor
      skills in other fields, including sports and rehabilitation, is promising enough
      to justify its utilization to improve surgical performance. However, some
      surgical procedures, especially ones performed during human-robot interaction in
      robot-assisted surgery, are much more complicated than sport and rehabilitation.
      Cognitive training has shown promising results in surgical skills-acquisition in
      complicated environments such as surgery. However, these methods are mostly
      developed in research groups using limited individuals. Transferring this
      research into the clinical applications is a demanding challenge. The aim of this
      review is to provide an overview of the current status of these novel cognitive
      training approaches in surgery and to investigate the potential role of cognitive
      training in surgical education.

PMID- 28445191
TI  - Evaluation of Horner Syndrome in the MRI Era.
AB  - BACKGROUND: To identify the etiologies of adult Horner syndrome (HS) in the MRI
      era using a targeted evaluation approach and to assess the value and yield of
      targeted imaging. METHODS: A retrospective chart review was performed of 200
      adult outpatients with HS, confirmed with cocaine eyedrop testing. Patients were
      divided into subgroups based on the presence or absence of symptoms and those who
      did or did not receive additional testing with hydroxyamphetamine drops. Imaging
      was obtained based on pharmacologic localization and/or clinical evaluation. The
      etiology of HS and the yield of imaging were determined in all subgroups.
      RESULTS: Imaging showed causative lesions in 24 of 179 (12.84%) imaged patients
      with HS, and 13 (69.0%) were determined "idiopathic." Of the patients who
      underwent testing with hydroxyamphetamine drops (132 patients), 86 had a
      postganglionic localization with an imaging yield of 8.1%, and 46 had
      preganglionic cause with an imaging yield of 21.7%. Fifty-three patients (26.5%)
      never noticed ptosis/anisocoria before examination, and the imaging yield in this
      subgroup was 2.8%. Eighteen of the 200 patients (9.0%) had serious pathology,
      including carotid artery dissection, brain, or neck mass, and 6 of these (31.6%)
      had acute symptoms and/or pain. CONCLUSIONS: HS is most often idiopathic with
      serious pathology being relatively infrequent. When determining etiology, the
      absence of symptoms is not predictive of the pathology. However, acute onset of
      symptoms and/or pain are possible indicators for serious pathology. Localizing
      the lesion using hydroxyamphetamine drops whenever obtainable and available is
      still an efficient way to target imaging evaluation.

PMID- 28445192
TI  - One-Year Clinical Outcomes of a Corneal Inlay for Presbyopia.
AB  - PURPOSE: To report the results of a 1-year follow-up analysis of the safety and
      efficacy of the Flexivue Microlens corneal inlay. METHODS: The Flexivue Microlens
      corneal inlay was implanted in the nondominant eye of patients with emmetropic
      presbyopia (a spherical equivalent of -0.5 to 1.00 diopter) after the creation of
      a 300-MUm deep stromal pocket, using a femtosecond laser. The patients were
      followed up according to a clinical protocol involving refraction, anterior
      segment imaging analysis (Oculyzer), and optical quality analysis (OPD-Scan).
      RESULTS: Thirty-one patients were enrolled in this ongoing study. The mean age
      was 50.7 years (range 45-60 yrs), and 70% of the patients were female. The mean
      uncorrected near visual acuity improved to Jaeger 1 in 87.1% of the eyes treated
      with the inlays. All eyes improved 4 lines at all visits. The binocular
      uncorrected distance visual acuity was 20/20 in all patients. Ninety percent of
      the patients reported that their near vision was good or excellent. Some of the
      patients (16.1%) lost more than 3 lines of corrected distance visual acuity. At
      the latest follow-up, induction of a corneal spherical aberration to improve near
      visual acuity was statistically significant. No other intraoperative or
      postoperative complication was noted. CONCLUSIONS: The Flexivue Microlens
      provided patients with improved near vision, as a result of a negative spherical
      aberration. A significant loss of corrected distance visual acuity in the
      operated eyes was observed. Overall, this intracorneal inlay was an effective
      alternative to other procedures for the correction of presbyopia.

PMID- 28445193
TI  - A Pilot Randomized Trial on Safety and Efficacy of a Novel Topical Combined
      Inhibitor of Janus Kinase 1/3 and Spleen Tyrosine Kinase for GVHD-Associated
      Ocular Surface Disease.
AB  - PURPOSE: Janus kinase (JAK) and spleen tyrosine kinase (SYK) play critical
      functions in T-cell activation and in inflammation. Because of their
      antiinflammatory effects, JAK and SYK inhibitors have recently been evaluated in
      several immunopathogenic disorders. This pilot study was designed to assess the
      safety and efficacy of a topical combined JAK/SYK inhibitor, R348, ophthalmic
      solution for treatment of ocular surface disease in graft-versus-host disease
      (GVHD). METHODS: This phase 2, double-masked, randomized, pilot trial included 30
      patients with ocular surface disease due to GVHD who were randomized to receive
      topical 0.5% R348, 0.2% R348, or vehicle, twice daily for 12 weeks. Before and
      after treatment, a comprehensive ophthalmic evaluation was performed, which
      included Ocular Surface Disease Index (OSDI) questionnaire, Ocular Comfort Index
      questionnaire, corneal fluorescein staining, conjunctival lissamine green
      staining, and Schirmer test with anesthesia. Changes in these parameters were
      compared between the 3 groups. RESULTS: The mean decrease in total corneal
      fluorescein staining at 12 weeks after treatment was higher in the 0.5% R348
      group (-6.0 +/- 3.9, NEI scoring) compared with the vehicle (-2.1 +/- 2.6, P =
      0.045) or the 0.2% R348 group (-4.1 +/- 3.6, P = 0.34). However, there were no
      significant differences among the groups in terms of treatment-induced changes in
      OSDI, Ocular Comfort Index, conjunctival lissamine green staining, or Schirmer
      scores. R348 eye drops were well tolerated. CONCLUSIONS: This pilot study
      indicates that 0.5% R348 JAK/SYK inhibitor ophthalmic solution is well tolerated
      and may have some therapeutic efficacy in treating ocular GVHD. Larger trials are
      required to derive more definitive data.

PMID- 28445195
TI  - Protective Effect of Botulinum Toxin Type A Against Atopic Dermatitis-Like Skin
      Lesions in NC/Nga Mice.
AB  - BACKGROUND: Botulinum neurotoxin (BTX) A possesses various biological activities,
      including anti-inflammatory and antipruritic actions. Human and animal studies
      have shown that BTX is effective in treating histamine-induced itch, lichen
      simplex chronicus, psoriasis, rosacea, allergic rhinitis, and scar prevention.
      However, its effect on atopic dermatitis (AD) has not been studied yet.
      OBJECTIVE: To examine the effect of BTX on AD using a mouse model. The primary
      outcome was skin thickness and transepidermal water loss (TEWL), and the
      secondary outcome was the alteration in skin severity scores, histological, and
      laboratory test results. METHODS: Forty-two NC/Nga mice (a mouse model for AD)
      were allocated into 6 groups (the untreated, 2-Chloro-1,3,5-trinitrobenzene
      [TNCB] alone, TNCB + BTX 30 U/kg, TNCB + BTX 60 U/kg, TNCB + vehicle [0.9%
      saline], TNCB + 0.03% tacrolimus). Those of the BTX group received intradermal
      injections of BTX on the rostral back once on the day of TNCB sensitization. The
      effect of BTX in TNCB-treated NC/Nga mice was assessed by measuring skin
      thickness, TEWL (primary outcome), the skin severity scores, histological changes
      of test skin including mast cell count, interleukin (IL)-4 mRNA and protein
      expression, and total serum IgE (secondary outcome). RESULTS: A single
      intradermal injection of BTX significantly suppressed skin thickness and TEWL in
      the TNCB-applied skin. The clinical severity scores, acanthosis and mast cell
      infiltration, were less in the BTX groups. BTX injection also inhibited TNCB
      induced increase in IL-4 mRNA and protein expression in mice, but its effect on
      serum IgE level was not significant. CONCLUSION: The preliminary results suggest
      that BTX may be a novel approach to the prevention and supplemental treatment of
      acute AD lesions.

PMID- 28445194
TI  - Successful Treatment of Stable Vitiligo by Low-Density Cultured Autologous
      Melanocyte Transplantation Combined With Narrowband Ultraviolet B Therapy.
AB  - BACKGROUND: Cultured autologous melanocyte transplantation (CMT) is an effective
      treatment for stable vitiligo, but the current method is time consuming and
      expensive because of the requirement of a large number of melanocytes. OBJECTIVE:
      To assess the clinical effect of low-density CMT combined with narrowband
      ultraviolet B (NB-UVB) in treating stable vitiligo. MATERIALS AND METHODS: The
      authors treated 8 patients with CMT at a low cell density (less than 2.5 * 10
      cells/cm). Among them, 6 patients underwent NB-UVB therapy after CMT. RESULTS:
      All the 6 patients treated with low-density CMT combined with NB-UVB obtained
      more than 90% repigmentation at the 1-year follow-up. CONCLUSION: The authors'
      data suggest that low-density CMT combined with NB-UVB can be an effective form
      of surgical treatment for stable vitiligo.

PMID- 28445196
TI  - The Use of a Fresh-Tissue Cadaver Model for the Instruction of Dermatological
      Procedures: A Laboratory Study for Training Medical Students.
AB  - BACKGROUND: A realistic model for the instruction of basic dermatologic
      procedural skills was developed, while simultaneously increasing medical student
      exposure to the field of dermatology. OBJECTIVE: The primary purpose of the
      authors' study was to evaluate the utilization of a fresh-tissue cadaver model
      (FTCM) as a method for the instruction of common dermatologic procedures. The
      authors' secondary aim was to assess students' perceived clinical skills and
      overall perception of the field of dermatology after the lab. METHODS: Nineteen
      first- and second-year medical students were pre- and post-tested on their
      ability to perform punch and excisional biopsies on a fresh-tissue cadaver.
      Students were then surveyed on their experience. RESULTS: Assessment of the
      cognitive knowledge gain and technical skills revealed a statistically
      significant improvement in all categories (p < .001). An analysis of the survey
      demonstrated that 78.9% were more interested in selecting dermatology as a career
      and 63.2% of participants were more likely to refer their future patients to a
      Mohs surgeon. CONCLUSION: An FTCM is a viable method for the instruction and
      training of dermatologic procedures. In addition, the authors conclude that an
      FTCM provides realistic instruction for common dermatologic procedures and
      enhances medical students' early exposure and interest in the field of
      dermatology.

PMID- 28445197
TI  - Saline Hydrodissection: A Novel Technique for the Injection of Calcium
      Hydroxylapatite Fillers in the Forehead.

PMID- 28445198
TI  - Mohs Micrographic Surgery for a Red Tattoo Reaction.

PMID- 28445199
TI  - Effect of Electroacupuncture at The Zusanli Point (Stomach-36) on Dorsal Random
      Pattern Skin Flap Survival in a Rat Model.
AB  - BACKGROUND: Random skin flaps are commonly used for wound repair and
      reconstruction. Electroacupuncture at The Zusanli point could enhance
      microcirculation and blood perfusion in random skin flaps. OBJECTIVE: To
      determine whether electroacupuncture at The Zusanli point can improve the
      survival of random skin flaps in a rat model. MATERIALS AND METHODS: Thirty-six
      male Sprague Dawley rats were randomly divided into 3 groups: control group (no
      electroacupuncture), Group A (electroacupuncture at a nonacupoint near The
      Zusanli point), and Group B (electroacupuncture at The Zusanli point). McFarlane
      flaps were established. On postoperative Day 2, malondialdehyde (MDA) and
      superoxide dismutase were detected. The flap survival rate was evaluated,
      inflammation was examined in hematoxylin and eosin-stained slices, and the
      expression of vascular endothelial growth factor (VEGF) was measured
      immunohistochemically on Day 7. RESULTS: The mean survival area of the flaps in
      Group B was significantly larger than that in the control group and Group A.
      Superoxide dismutase activity and VEGF expression level were significantly higher
      in Group B than those in the control group and Group A, whereas MDA and
      inflammation levels in Group B were significantly lower than those in the other 2
      groups. CONCLUSION: Electroacupuncture at The Zusanli point can effectively
      improve the random flap survival.

PMID- 28445200
TI  - The Nasal Tip Rotation Flap for Reconstruction of the Lateral Nasal Tip, Anterior
      Ala, and Soft Triangle: The Authors' Experience With 55 Patients.
AB  - BACKGROUND: Defects of the lateral nasal tip, anterior ala, and soft triangle
      subunits lack reconstructive options that are consistently satisfactory. For such
      defects, the novel anterior-based nasal tip rotation flap provides functional and
      aesthetic results in a single operative session. OBJECTIVE: To describe the
      authors' experience with the nasal tip rotation flap, including patient selection
      and design modifications to enhance aesthetic success. METHODS: An IRB-approved
      retrospective database review of nasal tip rotation flap repairs was performed at
      the Medical University of South Carolina and Stanford University Medical Center.
      The design and surgical technique of this flap are described and illustrated,
      emphasizing factors such as nasal shape and defect location in modifying flap
      design. RESULTS: The nasal tip rotation is a single-stage, local flap that
      provides optimal tissue match with recapitulation of the native topography of the
      nasal tip and incision lines that are well hidden at the junction of cosmetic
      subunits. The mechanics of the flap distribute closure tension widely across the
      alar rim without focal notching or airway compromise. CONCLUSION: The nasal tip
      rotation flap is a reliable, cosmetically elegant repair that fills a gap in the
      reconstructive options for anterior ala and soft triangle defects on the nose.

PMID- 28445201
TI  - The Utility of Color Doppler Ultrasound to Explore Vascular Complications After
      Filler Injection.

PMID- 28445202
TI  - Adnexal Carcinomas Treated With Mohs Micrographic Surgery: A Comprehensive
      Review.
AB  - BACKGROUND: Adnexal carcinomas (ACs) are rare cutaneous malignancies of sweat
      gland or pilosebaceous origin. Optimal treatment and metastatic potential of AC
      are poorly defined. Mohs micrographic surgery (MMS) has been increasingly used to
      treat AC. OBJECTIVE: To review selected primary cutaneous AC and their treatment
      outcomes with MMS. MATERIALS AND METHODS: Literature review using PubMed search
      for articles related to primary cutaneous ACs. RESULTS: Sebaceous carcinoma
      treated with MMS recurred and metastasized in 6.4% and 3.7%, respectively.
      Primary cutaneous mucinous carcinoma treated with MMS recurred and metastasized
      in 9.6% and 6.4%, respectively. After MMS, 4.7% of microcystic AC recurred with
      no reported metastases. After MMS, recurrences and metastases of trichilemmal
      carcinoma or hidradenocarcinoma have not been reported. Two (4.2%) regional lymph
      node metastases but no distant metastases or local recurrences have been reported
      in eccrine porocarcinoma. Squamoid eccrine duct tumor, pilomatrix carcinoma, and
      spiradenocarcinoma treated with MMS are also reviewed. CONCLUSION: The rarity of
      ACs and the lack of comparative data on treatment makes conclusive
      recommendations on treatment difficult. Recent large case series and reviews
      suggest MMS is a useful and possibly superior treatment for AC and should be
      considered if primary cutaneous disease is suspected.

PMID- 28445203
TI  - Considerations for refractive surgery in the glaucoma patient.
AB  - PURPOSE OF REVIEW: Given the popularity of keratorefractive surgery, and an aging
      populous of patients who have undergone these procedures, there is an increasing
      need for updated management protocols. This is particularly relevant for patients
      with chronic progressive diseases such as glaucoma, due to the variety of related
      diagnostic and management challenges inherent to these diseases. Here, we will
      review the current literature to provide an update on the management of patients
      with glaucoma who are undergoing, or have had laser ablative refractive surgery.
      Preoperative testing and eligibility considerations, intraoperative factors, and
      postoperative observation and follow-up will be discussed. RECENT FINDINGS:
      Intraoperative intraocular pressure (IOP) rise during flap creation is associated
      with low risk of acute complications, and furthermore do not appear to have
      significant long term effects. Modern technologies have improved our ability to
      determine accurate IOP after refractive surgery despite postoperative changes in
      corneal architecture. Furthermore, advances in structural imaging allow for
      earlier detection of even subtle glaucomatous nerve damage. SUMMARY: Although
      glaucoma remains a relative contraindication to refractive surgery, it is a safe
      procedure for many patients with appropriate perioperative management and follow
      up. Advancements in diagnostic modalities have allowed for earlier detection of
      glaucomatous disease, and subsequent earlier intervention when appropriate.
      Standardized diagnostic algorithms and rigorous perioperative assessment are
      critical to safe management of glaucoma patients undergoing refractive corneal
      surgery.

PMID- 28445204
TI  - Pediatric refractive surgery.
AB  - PURPOSE OF REVIEW: Refractive surgery procedures have been performed on children
      since the early 1980s. This article will review this history as well as current
      thoughts on treating children with large refractive errors. RECENT FINDINGS:
      Pediatric refractive surgery has developed slowly as very few children fit the
      criteria for treatment. For this reason, practice patterns are varied and
      publications are rare. Publications in recent years have focused on intraocular
      procedures over laser refractive surgery. SUMMARY: Pediatric refractive surgery
      is an evolving field as surgeons try to find the best long-term treatments for
      these young patients.

PMID- 28445205
TI  - Inhibition of microRNA-429 in the renal medulla increased salt sensitivity of
      blood pressure in Sprague Dawley rats.
AB  - BACKGROUND: We have previously shown that high salt intake suppresses the
      expression of prolyl hydroxylase domain-containing protein 2 (PHD2), an enzyme
      promoting the degradation of hypoxia-inducible factor (HIF)-1alpha, and increases
      HIF-1alpha along with its target genes in the renal medulla, which promotes
      sodium excretion and regulates salt sensitivity of blood pressure. However, it
      remains unknown how high salt inhibits the expression of PHD2. METHOD AND
      RESULTS: The current study first revealed that high-salt-induced PHD2 inhibition
      was due to the enhanced decay of mRNA. We then found that high salt significantly
      increased the expression of miR-429, which was subsequently proven to target the
      3'-untranslated region of PHD2 and reduce PHD2 levels, in the renal medulla. To
      define the functional role of renal medullary miR-429 in the regulation of
      PHD2/HIF-1alpha-mediated renal adaptation to high salt intake and salt
      sensitivity of blood pressure, we locally inhibited miR-429 in the renal medulla
      by locked nucleic acid anti-miR-429 in uninephrectomized rats. Our results
      demonstrated that inhibition of miR-429 remarkably increased the levels of PHD2,
      which disrupted PHD2-associated adaptive activation of HIF-1alpha-mediated gene
      expression in response to high salt in the renal medulla and consequently
      inhibited urinary sodium excretion, enhanced sodium retention in response to
      chronic sodium overloading, and as a result, produced a salt-sensitive
      hypertension. CONCLUSION: It is concluded that miR-429 is an important upstream
      mediator in PHD2/HIF-1alpha-associated renal adaptation to high salt intake and
      that deficiency in miR-429-mediated PHD2 inhibition in response to high salt in
      the renal medulla may represent a pathogenic mechanism for salt-sensitive
      hypertension.

PMID- 28445206
TI  - Independent effects of blood pressure and parathyroid hormone on aortic pulse
      wave velocity in untreated Chinese patients.
AB  - OBJECTIVE: Whether or not calcium-regulating hormones stiffen arteries
      independent of blood pressure (BP) is uncertain. We investigated the independent
      associations of carotid-femoral pulse wave velocity (PWV) with 25-hydroxy-vitamin
      D [25(OH)D], parathyroid hormone (PTH) and 24-h ambulatory BP in untreated
      Chinese patients. METHODS: Consecutive untreated patients referred for ambulatory
      BP monitoring were recruited. PWV was measured with a high-fidelity
      micromanometer and the SphygmoCor software (AtCor Medical, West Ryde, New South
      Wales, Australia). Serum 25(OH)D and PTH were determined by
      electrochemiluminescence immunoassay. Analysis of variance, single and multiple
      regressions were applied for analyses. RESULTS: In 1052 untreated patients (50.7%
      women; mean age, 51 years), PWV averaged 7.8 m/s, 24-h SBP/DBP 126.5/81.7 mmHg,
      serum 25(OH)D and PTH 36.0 nmol/l and 61.6 pg/ml, respectively. In multivariable
      adjusted analyses, BP (P < 0.001) and PTH (P = 0.012) increased from less than
      25th to at least 75th percentile of the PWV distribution. In continuous analyses,
      PWV independently increased by 0.40/0.23 m/s per 1-SD increment in SBP/DBP (P <
      0.001) and by 0.14 m/s for a doubling of serum PTH (P = 0.029). Associations of
      PWV with BP were tighter than with PTH (P < 0.001). In pathway analysis, the
      effect of PTH on PWV did not run via serum or urinary calcium (P = 0.65), but PTH
      had both a direct (P = 0.026) and a BP-mediated indirect effect (P = 0.043) on
      PWV. In none of our analyses were PWV associated with serum 25(OH)D. CONCLUSION:
      Arterial stiffness, as assessed by PWV, independently increased both with BP and
      with PTH, but BP remains the main driver of arterial stiffening.

PMID- 28445207
TI  - Effect of renal sympathetic denervation on short-term blood pressure variability
      in resistant hypertension: a meta-analysis.
AB  - BACKGROUND/OBJECTIVES: Short-term blood pressure variability (BPV) is affected by
      multiple factors including the sympathetic nervous system drive. Regarding the
      latter, the novel interventional technology of renal denervation (RDN), by
      modulating the sympathetic system activation, could have a beneficial impact on
      BPV. The aim of the current study is to review and meta-analyze the available
      evidence on the effect of RDN on short-term BPV. METHODS: We searched
      Medline/PubMed database until October 2016 for studies with eligible content. We
      performed random-effect meta-analyses for 12 outcomes of interest: the standard
      deviation (SD) of SBP (24 h, daytime and night-time) and DBP (24 h, daytime and
      night-time), the weighted SD of SBP and DBP across 24 h, the coefficient of
      variation of SBP and DBP across 24 h and the average real variability of SBP and
      DBP across 24 h. RESULTS: RDN reduced the SD of SBP across 24 h [mean change: 
      1.212 (95% confidence intervals (CIs): -2.354/-0.071), P = 0.037] and decreased
      the SD of systolic daytime BP [mean difference: -1.617 (95% CIs: -3.21/-0.026), P
      = 0.046] and diastolic daytime BP (marginally) [mean difference: -2.605 (95% CIs:
      -5.21/-0.003), P = 0.05]. The effect of RDN in reducing SD of SBP across 24 h or
      DBP across daytime was not influenced by absolute or relative reduction in SBP
      and DBP indices. (P > 0.1 for all). CONCLUSION: Catheter-based RDN in resistant
      hypertensive patients can favorably affect short-term BPV, independent of the
      level of BP reduction. Further investigation of the effect of RDN on BPV is
      needed with large randomized trials.

PMID- 28445208
TI  - Toxic Keratoconjunctivitis.
AB  - Toxic keratoconjunctivitis (TK) is an underrecognized complication of ophthalmic
      drug use and various environmental or occupational exposures. A detailed history
      and clinical examination are important to identify the offending agent(s). Common
      drug-related causes of TK include preservatives in ophthalmic medications,
      topical antimicrobials, and topical anesthetics. Alternatives to benzalkonium
      chloride as well as preservative-free formulations should be considered in
      patients requiring long-term topical medication. More advanced cases of TK may
      require preservative-free topical steroids and/or antibiotics, and occasionally
      surgical intervention. Early recognition and appropriate management of TK may
      help prevent permanent ocular and visual damage.

PMID- 28445209
TI  - Intelligence and Interleukin-6 in Older Adults: The Role of Repetitive Thought.
AB  - OBJECTIVE: Higher intelligence quotient (IQ) correlates with lower systemic
      inflammation, consistent with an association between lower IQ and disease risk.
      The present study examined the role of repetitive thought (RT) in the
      relationship between IQ and interleukin (IL)-6. RT is thinking attentively,
      repeatedly, and frequently about oneself and one's world and is characterized by
      valence (positive-negative), purpose (searching-solving), and total quantity
      (much-little). METHODS: Estimated IQ and RT dimension scores were assessed at
      baseline in a sample of older adults (N = 120, mean age = 74 years), who
      thereafter had blood drawn up to 10 times semiannually (n = 799). Models were
      adjusted for body mass index, chronological age, and statin medication. RESULTS:
      Higher IQ was associated with lower IL-6 (gamma = -0.225, SE = 0.111, p = .045).
      Of the RT dimensions, only more total RT predicted lower IL-6 (gamma = -0.037, SE
      = 0.011, p = .001), an effect that was not moderated by valence or purpose. More
      total RT accounted for part of the effect of IQ on IL-6 (indirect effect = -0.06
      [confidence interval = -0.14 to -0.002]). There was also a significant
      interaction between IQ and total RT (F(1,119) = 6.97, p = .009), in which more
      total RT was more strongly associated with lower IL-6 for people with lower IQ.
      CONCLUSIONS: Although some forms of RT such as worry may have negative health
      correlates for older adults, engaging in RT per se can be healthy insofar as it
      also encompasses planning, processing, and coping. Older adults with higher IQ
      were more likely to engage in RT, but those with average IQ benefitted the most
      with regard to a marker of systemic inflammation.

PMID- 28445210
TI  - Perceived Discrimination and Longitudinal Change in Kidney Function Among Urban
      Adults.
AB  - OBJECTIVE: Perceived discrimination has been associated with psychosocial
      distress and adverse health outcomes. We examined associations of perceived
      discrimination measures with changes in kidney function in a prospective cohort
      study, the Healthy Aging in Neighborhoods of Diversity across the Life Span.
      METHODS: Our study included 1620 participants with preserved baseline kidney
      function (estimated glomerular filtration rate [eGFR] >= 60 mL/min/1.73 m) (662
      whites and 958 African Americans, aged 30-64 years). Self-reported perceived
      racial discrimination and perceived gender discrimination (PGD) and a general
      measure of experience of discrimination (EOD) ("medium versus low," "high versus
      low") were examined in relation to baseline, follow-up, and annual rate of change
      in eGFR using multiple mixed-effects regression (gammabase, gammarate) and
      ordinary least square models (gammafollow). RESULTS: Perceived gender
      discrimination "high versus low PGD" was associated with a lower baseline eGFR in
      all models (gammabase = -3.51 (1.34), p = .009 for total sample). Among white
      women, high EOD was associated with lower baseline eGFR, an effect that was
      strengthened in the full model (gammabase = -5.86 [2.52], p = .020). Overall,
      "high versus low" PGD was associated with lower follow-up eGFR (gammafollow = 
      3.03 [1.45], p = .036). Among African American women, both perceived racial
      discrimination and PGD were linked to lower follow-up kidney function, an effect
      that was attenuated with covariate adjustment, indicating mediation through
      health-related, psychosocial, and lifestyle factors. In contrast, EOD was not
      linked to follow-up eGFR in any of the sex by race groups. CONCLUSIONS: Perceived
      racial and gender discrimination are associated with lower kidney function
      assessed by glomerular filtration rate and the strength of associations differ by
      sex and race groups. Perceived discrimination deserves further investigation as a
      psychosocial risk factors for kidney disease.

PMID- 28445211
TI  - POLYPOIDAL CHOROIDAL VASCULOPATHY ASSOCIATED WITH CENTRAL SEROUS
      CHORIORETINOPATHY: Pachychoroid Spectrum of Diseases.
AB  - PURPOSE: To study multimodal imaging features of polypoidal choroidal
      vasculopathy (PCV) associated with central serous chorioretinopathy (CSC) in the
      same eye. METHODS: A retrospective observational study of cases of suspected PCV
      which underwent indocyanine green angiography, fundus fluorescein angiography and
      optical coherence tomography was done, to look for simultaneous typical CSC-like
      active leak in the same eye. The relevant history, best-corrected visual acuity,
      optical coherence tomography, fundus fluorescein angiography, and indocyanine
      green angiography findings were analyzed. RESULTS: From 226 patients reviewed,
      195 patients had PCV from which 6 eyes (3.07%) with features of PCV associated
      with typical CSC-like active leak in the same eye were identified; 3 men and 3
      women with a mean age of 62.6 years. Optical coherence tomography showed notched
      pigment epithelial detachment in two and irregular peaked pigment epithelial
      detachment in four cases with subretinal fluid and/or subretinal haemorrhage over
      a thick choroid with dilated outer choroidal vessels. Fundus fluorescein
      angiography showed stippled hyperfluorescence at polyp area and a separate
      typical CSC-like active leak-Inkblot in three and Smokestack in three cases. On
      indocyanine green angiography, multiple polyps were noted with choroidal
      hyperpermeability in late phase at the site of CSC leak. CONCLUSION: The
      coexistence of PCV with typical CSC-like active leaks and a thick choroid in the
      same eye simultaneously provides strong evidence that these diseases have an
      association and support the hypothesis that these conditions may originate from
      predisposed thick choroid.

PMID- 28445212
TI  - Plasma Concentration of Itraconazole in Patients With Hematologic Malignancies
      Treated With Itraconazole Oral Solution.
AB  - BACKGROUND: The prophylactic administration of itraconazole (ITCZ) is effective
      for preventing mycotic infections during chemotherapy in patients with
      hematologic malignancies. However, fungal infections can occur when the ITCZ does
      not reach an effective concentration. METHODS: We conducted a prospective study
      to monitor the plasma concentration of ITCZ and hydroxyl-ITCZ (OH-ITCZ) weekly
      and to verify whether the day 3 plasma concentration of ITCZ could predict the
      subsequent acquisition of an effective plasma concentration. RESULTS: A total of
      39 patients who underwent 66 courses of chemotherapy were assessed in this study.
      An effective plasma concentration was achieved on day 7 in 34 of 63 patients
      (54%) and on day 14 in 35 of 59 patients (59%). A univariate analysis revealed
      that age, type of chemotherapy, and the body surface area were significantly
      associated with a high plasma concentration of ITCZ + OH-ITCZ. A linear
      regression analysis extracted the body surface area and the type of chemotherapy
      as significant factors. An receiver operating characteristic curve analysis
      revealed a day 3 plasma ITCZ + OH-ITCZ concentration of >656 ng/mL led to a
      plasma concentration that exceeded the minimum effective level on day 7; the
      sensitivity and specificity were 62% and 93%, respectively. CONCLUSIONS: This
      study showed that the measurement of the day 3 plasma concentration could lead to
      a better outcome in patients receiving chemotherapy for hematologic malignancies.

PMID- 28445213
TI  - Learner, Patient, and Supervisor Features Are Associated With Different Types of
      Cognitive Load During Procedural Skills Training: Implications for Teaching and
      Instructional Design.
AB  - PURPOSE: Cognitive load theory, focusing on limits of the working memory, is
      relevant to medical education; however, factors associated with cognitive load
      during procedural skills training are not well characterized. The authors sought
      to determine how features of learners, patients/tasks, settings, and supervisors
      were associated with three types of cognitive load among learners performing a
      specific procedure, colonoscopy, to identify implications for procedural
      teaching. METHOD: Data were collected through an electronically administered
      survey sent to 1,061 U.S. gastroenterology fellows during the 2014-2015 academic
      year; 477 (45.0%) participated. Participants completed the survey immediately
      following a colonoscopy. Using multivariable linear regression analyses, the
      authors identified sets of features associated with intrinsic, extraneous, and
      germane loads. RESULTS: Features associated with intrinsic load included learners
      (prior experience and year in training negatively associated, fatigue positively
      associated) and patient/tasks (procedural complexity positively associated,
      better patient tolerance negatively associated). Features associated with
      extraneous load included learners (fatigue positively associated), setting (queue
      order positively associated), and supervisors (supervisor engagement and
      confidence negatively associated). Only one feature, supervisor engagement, was
      (positively) associated with germane load. CONCLUSIONS: These data support
      practical recommendations for teaching procedural skills through the lens of
      cognitive load theory. To optimize intrinsic load, level of experience and
      competence of learners should be balanced with procedural complexity; part-task
      approaches and scaffolding may be beneficial. To reduce extraneous load, teachers
      should remain engaged, and factors within the procedural setting that may
      interfere with learning should be minimized. To optimize germane load, teachers
      should remain engaged.

PMID- 28445214
TI  - Teaching the Social Determinants of Health: A Path to Equity or a Road to
      Nowhere?
AB  - Medical schools are increasingly called to include social responsibility in their
      mandates. As such, they are focusing their attention on the social determinants
      of health (SDOH) as key drivers in the health of the patients and communities
      they serve. However, underlying this emphasis on the SDOH is the assumption that
      teaching medical students about the SDOH will lead future physicians to take
      action to help achieve health equity. There is little evidence to support this
      belief. In many ways, the current approach to the SDOH within medical education
      positions them as "facts to be known" rather than as "conditions to be challenged
      and changed." Educators talk about poverty but not oppression, race but not
      racism, sex but not sexism, and homosexuality but not homophobia. The current
      approach to the SDOH may constrain or even incapacitate the ability of medical
      education to achieve the very goals it lauds, and in fact perpetuate inequity. In
      this article, the authors explore how "critical consciousness" and a recentering
      of the SDOH around justice and inequity can be used to deepen collective
      understanding of power, privilege, and the inequities embedded in social
      relationships in order to foster an active commitment to social justice among
      medical trainees. Rather than calling for minor curricular modifications, the
      authors argue that major structural and cultural transformations within medical
      education need to occur to make educational institutions truly socially
      responsible.

PMID- 28445215
TI  - Promoting Learning and Patient Care Through Shared Reflection: A Conceptual
      Framework for Team Reflexivity in Health Care.
AB  - Health care teams are groups of highly skilled experts who may often form
      inexpert teams because of a lack of collective competence. Because teamwork and
      collaboration form the foundation of effective clinical practice, factors that
      promote collective competence demand exploration. The authors review team
      reflexivity (TR), a concept from the psychology and management literatures, and
      how it could contribute to the collective competence of health care teams. TR
      captures a team's ability to reflect collectively on group objectives,
      strategies, goals, processes, and outcomes of past, current, and future
      performance to process key information and adapt accordingly. As an overarching
      process that promotes team functioning, TR builds shared mental models as well as
      triggering team adaptation and learning.The authors present a conceptual
      framework for TR in health care, describing three phases in which TR may occur:
      pre-action TR (briefing before patient care), in-action TR (deliberations during
      active patient care), and post-action TR (debriefing after patient care).
      Depending on the phase, TR targets either goals, taskwork, teamwork, or resources
      and leads to different outcomes (e.g., optimal preparation, a shared mental
      model, adaptation, or learning). This novel conceptual framework incorporates
      various constructs related to reflection and unites them under the umbrella of
      TR. Viewing reflection through a team lens may guide future research about team
      functioning, optimize training efforts, and elucidate mechanisms for workplace
      learning, with better patient care as the ultimate goal.

PMID- 28445216
TI  - Opposition to Obamacare: A Closer Look.
AB  - Prior telephone surveys have reported two main reasons for opposition to the
      Affordable Care Act (ACA): distrust of government and opposition to the universal
      coverage mandate. The authors set out to elucidate the reasons for this
      opposition. This article describes how the authors used qualitative methods with
      semistructured interviewing as a principal investigative method to gather
      information from people they met while bicycling across the United States from
      April through July 2016. During this time, the authors conducted open-ended,
      semistructured conversations with people they met as they rode their bicycles
      from Washington, DC, to Seattle, Washington. Informants were chosen as a
      convenience sample. One hundred sixteen individuals participated as informants.
      The majority of comments were negative toward the ACA. Conversations were
      categorized into four themes, which included the following: (1) The ACA has
      increased the cost of health insurance; (2) government should not tell people
      what to do; (3) responsibility for ACA problems is diffuse; and (4) the ACA
      should not pay for other people's problems. These face-to-face conversations
      indicated that opposition to the ACA may be due to the fact that many Americans
      have experienced an increase in the cost of insurance either through increased
      premiums or greatly increased deductibles. They blame this increase in cost on
      the ACA, President Obama, the government or insurance companies, and the
      inclusion of "others" in insurance plans. The authors discuss how these findings
      can influence medical education curricula to better prepare future physicians to
      discuss health policy issues with patients.

PMID- 28445217
TI  - Why Health Insurance Matters-and Why Research Evidence Should Too.
AB  - In the current debate over the future of the Affordable Care Act (ACA), research
      evidence on the impact of the law and the effects of health insurance coverage in
      general is critical. Studies of health insurance expansion over the past decade
      have demonstrated that coverage expansions can produce significant reductions in
      mortality-particularly among minorities, those living in poorer areas, and those
      with chronic conditions potentially treatable with timely medical care. More
      recent studies of the ACA in particular demonstrate that the law has produced
      historically large reductions in the uninsured rate, with resulting improvements
      in access to care, perceived quality of care, and self-reported health. Yet much
      of the general public and many policy makers remain unaware of this evidence.
      Researchers and clinicians in academic medicine have a role to play in ensuring
      that critically important health policy decisions are made using rigorous
      evidence to best protect the interests of our patients.

PMID- 28445218
TI  - A Study of Pediatricians' Debt Repayment a Decade After Completing Residency.
AB  - PURPOSE: Pediatricians' education debt has been increasing. Less is known about
      the pace of their debt repayment. The authors examined patterns of debt repayment
      for pediatricians who completed residency from 2002-2004. METHOD: The authors
      analyzed weighted 2013 survey data from the American Academy of Pediatrics
      Pediatrician Life and Career Experience Study. They categorized participants
      based on education debt level at residency completion ($0; $1-$49,999; $50,000
      $99,999; $100,000-$149,999; >= $150,000) and explored debt repayment and well
      being by starting debt group using multivariable logistic regression. RESULTS: Of
      830 pediatricians surveyed, 266 (32%) had no starting debt and 166 (20%) had >=
      $150,000 in starting debt. A decade after residency, the percentage of
      participants who completely repaid their debt varied from 76% (68/89) of those
      with $1-$49,999 of starting debt to 15% (25/164) of those with >= $150,000 of
      starting debt. The percentage of participants concerned about their debt
      increased with starting debt level, with over half of those in the highest group
      concerned. Starting debt was associated with all examined measures of debt
      repayment and with recent financial difficulties among those in the two highest
      debt groups ($100,000-$149,999: adjusted odds ratio = 3.82, confidence interval =
      1.17-12.43; >= $150,000: adjusted odds ratio = 4.55, confidence interval = 1.47
      14.14). CONCLUSIONS: A decade after completing residency, pediatricians had made
      progress repaying their debt, yet many still expressed concern, especially those
      with the greatest amount of starting debt. As debt levels continue to increase,
      these issues could worsen.

PMID- 28445219
TI  - Canadian National Guidelines and Recommendations for Integrating Career Advising
      Into Medical School Curricula.
AB  - Career planning, decision making about specialty choice, and preparation for
      residency matching are significant sources of stress for medical students.
      Attempts have been made to structure and formalize career advising by including
      it in accreditation standards. There is an expressed need for national guidelines
      on career advising for medical students. The Future of Medical Education in
      Canada Postgraduate (FMEC PG) Implementation Project was created to ensure
      Canadian medical trainees receive the best education possible. From this, a
      diverse sub-working group (SWG), representing different Canadian regions, was
      formed to review career advising processes across the country. The SWG developed,
      through a modified formal consensus methodology, a strategy for medical student
      career advising that is adaptable to all schools in alignment with existing
      accreditation standards. The SWG outlined five guiding principles and five
      essential elements for Canadian universities offering an MD degree with
      recommendations on how to integrate the elements into each school's career
      advising system. The five essential elements are a structured approach to career
      advising, information about available career options, elective guidance,
      preparation for residency applications, and social accountability. This
      Perspective endorses the view of the FMEC PG Implementation Project that national
      guidelines are important to ensure Canadian medical schools are consistently
      meeting accreditation standards by providing reliable and quality career advising
      to all medical students. The SWG's position, based on national and provincial
      feedback, is that these guidelines will stimulate discourse and action regarding
      the requirements and processes to carry out these recommendations nationwide and
      share across borders.

PMID- 28445220
TI  - Catalyzing Interdisciplinary Research and Training: Initial Outcomes and
      Evolution of the Affinity Research Collaboratives Model.
AB  - Team science has been recognized as critical to solving increasingly complex
      biomedical problems and advancing discoveries in the prevention, diagnosis, and
      treatment of human disease. In 2009, the Evans Center for Interdisciplinary
      Biomedical Research (ECIBR) was established in the Department of Medicine at
      Boston University School of Medicine as a new organizational paradigm to promote
      interdisciplinary team science. The ECIBR is made up of affinity research
      collaboratives (ARCs), consisting of investigators from different departments and
      disciplines who come together to study biomedical problems that are relevant to
      human disease and not under interdisciplinary investigation at the university.
      Importantly, research areas are identified by investigators according to their
      shared interests. ARC proposals are evaluated by a peer review process, and
      collaboratives are funded annually for up to three years.Initial outcomes of the
      first 12 ARCs show the value of this model in fostering successful biomedical
      collaborations that lead to publications, extramural grants, research networking,
      and training. The most successful ARCs have been developed into more sustainable
      organizational entities, including centers, research cores, translational
      research projects, and training programs.To further expand team science at Boston
      University, the Interdisciplinary Biomedical Research Office was established in
      2015 to more fully engage the entire university, not just the medical campus, in
      interdisciplinary research using the ARC mechanism. This approach to promoting
      team science may be useful to other academic organizations seeking to expand
      interdisciplinary research at their institutions.

PMID- 28445221
TI  - Changes in Personal Relationships During Residency and Their Effects on Resident
      Wellness: A Qualitative Study.
AB  - PURPOSE: Residency poses challenges for residents' personal relationships.
      Research suggests residents rely on family and friends for support during their
      training. The authors explored the impact of residency demands on residents'
      personal relationships and the effects changes in those relationships could have
      on their wellness. METHOD: The authors used a constructivist grounded theory
      approach. In 2012-2014, they conducted semistructured interviews with a purposive
      and theoretical sample of 16 Canadian residents from various specialties and
      training levels. Data analysis occurred concurrently with data collection,
      allowing authors to use a constant comparative approach to explore emergent
      themes. Transcripts were coded; codes were organized into categories and then
      themes to develop a substantive theory. RESULTS: Residents perceived their
      relationships to be influenced by their evolving professional identity: Although
      personal relationships were important, being a doctor superseded them.
      Participants suggested they were forced to adapt their personal relationships,
      which resulted in the evolution of a hierarchy of relationships that was
      reinforced by the work-life imbalance imposed by their training. This poor work
      life balance seemed to result in relationship issues and diminish residents'
      wellness. Participants applied coping mechanisms to manage the conflict arising
      from the adaptation and protect their relationships. To minimize the effects of
      identity dissonance, some gravitated toward relationships with others who shared
      their professional identity or sought social comparison as affirmation.
      CONCLUSIONS: Erosion of personal relationships could affect resident wellness and
      lead to burnout. Educators must consider how educational programs impact
      relationships and the subsequent effects on resident wellness.

PMID- 28445222
TI  - Development of an HIV Postexposure Prophylaxis (PEP) Protocol for Trainees
      Engaging in Academic Global Health Experiences.
AB  - PROBLEM: Global health (GH) education programs have become increasingly common in
      U.S. medical schools and graduate medical education programs, with growing
      numbers of medical students, residents, and fellows participating in clinical
      experiences in settings with high HIV prevalence and limited resources. However,
      there are no guidelines for provision of HIV postexposure prophylaxis (PEP) to
      trainees engaging in these academic GH experiences. APPROACH: Faculty of the
      Global Health Education Programs (GHEP) at the David Geffen School of Medicine at
      UCLA and GH partner institutions recognized the need for PEP access for trainees
      engaged in GH experiences. In 2013-2014, key UCLA faculty collaborated in the
      development of the UCLA GHEP PEP Protocol, which includes provision of PEP
      medications to trainees prior to departure, an on-call infectious disease/HIV
      specialist to advise trainees who have exposures, and a system for following up
      with exposed trainees while on the GH rotation and after their return. OUTCOMES:
      Between February 2014 and September 2016, 112 medical students and 110 residents
      received education on the PEP protocol during their predeparture orientation. The
      protocol was used for 28 exposures (27 occupational, 1 nonoccupational), with PEP
      recommended in 3 occupational cases (all needlesticks) and the single
      nonoccupational case. There were no reported HIV seroconversions. NEXT STEPS: The
      authors plan to formally evaluate the PEP protocol, conduct a qualitative
      assessment with trainees and both UCLA and GH partner faculty, and discuss best
      practices with institutions across the United States and with GH partners.

PMID- 28445223
TI  - The Four-Tier Continuum of Academic and Behavioral Support (4T-CABS) Model: An
      Integrated Model for Medical Student Success.
AB  - Not all students cope successfully with the demands of medical school, and
      students' struggles may result in study delay or dropout. To prevent these
      outcomes, medical schools need to identify students who are experiencing academic
      difficul ties and provide them with timely interventions through access to
      support programs. Although the importance of early identification and
      intervention is well recognized, less is known about successful strategies for
      identifying and supporting struggling students.Building on the literature and
      their own empirical findings, the authors propose an integrated, school-wide
      model for medical student success comprising a continuum of academic and
      behavioral support. This Four-Tier Continuum of Academic and Behavioral Support
      (4T-CABS) model focuses on improving both academic and behavioral outcomes by
      offering support for students at four levels, which range from adequate
      instruction for all, to targeted small-group interventions, to individualized
      support, and also include exit support for students who might be better off in
      another degree program. Additionally, medical schools should provide both
      academic and behavioral support; set high, yet realistic expectations and clearly
      communicate these to students; and intervene early, which requires timely
      identification of at-risk students who would benefit from the different types and
      tiers of support. Finally, interventions should be evidence based and fit the
      needs of the identified groups of students. The authors argue that adopting the
      core principles of the 4T-CABS model will enable medical schools to maximize
      academic engagement and performance for all students.

PMID- 28445224
TI  - Impact of 6 consecutive days of sprint training in hypoxia on performance in
      competitive sprint runners.
AB  - The purpose of the present study was to determine the effects of 6 successive
      days of repeated sprint training in moderate hypoxia on anaerobic capacity in 100
      200-m sprint runners. Eighteen male sprint runners (age, 20.0 +/- 0.3 years;
      height, 175.9 +/- 1.1 cm; body mass, 65.0 +/- 1.2 kg) performed repeated cycling
      sprints for 6 consecutive days in either normoxic (NOR; fraction of inspired
      oxygen [FiO2], 20.9%; n = 9) or hypoxic conditions (HYPO; FiO2, 14.5%; n = 9).
      The repeated sprint ability (10 * 6-s sprints), 30-s maximal sprint ability,
      maximal oxygen uptake (VO2max), and 60-m running time on the track were measured
      before and after the training period. Intramuscular PCr content (quadriceps
      femoris muscle) was measured by P-magnetic resonance spectroscopy (P-MRS) before
      and after the training period. Both groups showed similar improvements in
      repeated sprint ability after the training period (P<0.05). Power output during
      the 30-s maximal sprint test and VO2max did not change significantly after the
      training period in either group. Running time for 0-10m improved significantly
      after the training period in the HYPO only (before, 1.39 +/- 0.01s; after, 1.34
      +/- 0.02s, P<0.05). The HYPO also showed a significant increase in intramuscular
      PCr content after the training period (before, 31.5 +/- 1.3 mM; after, 38.2 +/-
      2.8 mM, P<0.05). These results suggest that sprint training for 6 consecutive
      days in hypoxia or normoxia improved repeated sprint ability in competitive
      sprint runners.

PMID- 28445225
TI  - Physical Fitness and Body Composition in 8-10-Year-Old Danish Children Are
      Associated With Sports Club Participation.
AB  - Larsen, MN, Nielsen, CM, Orntoft, CO, Randers, M, Manniche, V, Hansen, L, Hansen,
      PR, Bangsbo, J, and Krustrup, P. Physical fitness and body composition in 8-10
      year-old Danish children are associated with sports club participation. J
      Strength Cond Res 31(12): 3425-3434, 2017-We investigated whether physical
      fitness and body composition in 8-10-year-old Danish children are associated with
      sports club participation. The study included 423 schoolchildren, comprising 209
      girls and 214 boys, of whom 67 and 74%, respectively, were active in sports
      clubs. Yo-Yo intermittent recovery level 1 for children (YYIR1C), balance, jump
      and coordination tests, together with dual-energy X-ray absorptiometry, were used
      to determine exercise capacity and body composition. Children active in sports
      clubs had better (p < 0.05) YYIR1C (33%, 767 +/- 26 vs. 575 +/- 29 m), 20-m
      sprint (3%, 4.33 +/- 0.03 vs. 4.48 +/- 0.04 seconds), coordination (6%, 68 +/- 1
      vs. 72 +/- 1 second), and balance test performances (9%, 19.3 +/- 0.5 vs. 21.2 +/
      0.7 falls.min) and lower fat mass index (16%, 3.8 +/- 0.1 vs. 4.5 +/- 0.2
      kg[fat].m) than children not active in sports clubs. Ball game players had better
      (p < 0.05) YYIR1C (38%, 925 +/- 39 vs. 671 +/- 28 m), 20-m sprint (4%, 4.25 +/-
      0.03 vs. 4.42 +/- 0.04 seconds), and coordination test performances (5%, 65 +/- 1
      vs. 69 +/- 1 second), along with higher (p < 0.05) lean body mass (5%, 24.00 +/-
      0.22 vs. 22.83 +/- 0.25 kg) and whole-body BMD (2%, 0.90 +/- < 0.01 vs. 0.88 +/-
      <0.01 g.cm) compared with children active in other sports. The study showed that
      8[FIGURE DASH]10-year-old Danish children engaged in sports-club activity,
      especially ball game players, have better exercise capacity and superior body
      composition compared with children not active in sports clubs.

PMID- 28445226
TI  - Comparison of Training Intensity Patterns for Cardiorespiratory, Speed, and
      Strength Exercise Programs.
AB  - Vetter, RE, Yu, H, Foose, AK, Adam, PJ, and Dodd, RK. Comparison of training
      intensity patterns for cardiorespiratory, speed, and strength exercise programs.
      J Strength Cond Res 31(12): 3372-3395, 2017-Designing effective exercise training
      programs is important for novice, regular, and elite individuals desiring
      improvements in physical fitness and performance outcomes without experiencing
      deleterious physiological or performance effects. The purpose of this research
      was to understand the impact of training intensity on the effectiveness of
      training program outcomes. Synthesized analyses of 31 studies provided an overall
      magnitude for the impact of training program intensity on effect size (ES). Meta
      analyses were performed using meta-regression models to assess the impact of
      training program intensity and the other moderators of training frequency,
      training weeks, age, ability level, and type of physical exercise training.
      Inclusion criteria were (a) pretest and posttest outcomes, group size, and mean
      and SDs were given, (b) only human participants, age 17 or older, and healthy
      being free of disease, injury, or pregnancy, (c) no supplements or dietary
      interventions were used, (d) a minimum 4-week training intervention was used, and
      (e) training protocols included training intensity as its focus. Of the research
      reviewed, there were 31 studies representing 292 cases used to calculate ES,
      which met the inclusion criteria. Training frequency, training weeks, age, and
      ability level did not consistently affect the effectiveness of the different
      training programs. Intensity level influenced ES across the types of physical
      training programs: cardiorespiratory, muscular strength, or speed. An aggregated
      model had a curvilinear effect on training programs with an estimated critical
      average value of 74%. Muscular strength training using intensities greater than
      estimated 87.29% resulted in diminishing returns.

PMID- 28445227
TI  - A Review of Player Monitoring Approaches in Basketball: Current Trends and Future
      Directions.
AB  - Fox, JL, Scanlan, AT, and Stanton, R. A review of player monitoring approaches in
      basketball: current trends and future directions. J Strength Cond Res 31(7): 2021
      2029, 2017-Effective monitoring of players in team sports such as basketball
      requires an understanding of the external demands and internal responses, as they
      relate to training phases and competition. Monitoring of external demands and
      internal responses allows coaching staff to determine the dose-response
      associated with the imposed training load (TL), and subsequently, if players are
      adequately prepared for competition. This review discusses measures reported in
      the literature for monitoring the external demands and internal responses of
      basketball players during training and competition. The external demands of
      training and competition were primarily monitored using time-motion analysis,
      with limited use of microtechnology being reported. Internal responses during
      training were typically measured using hematological markers, heart rate, various
      TL models, and perceptual responses such as rating of perceived exertion (RPE).
      Heart rate was the most commonly reported indicator of internal responses during
      competition with limited reporting of hematological markers or RPE. These
      findings show a large discrepancy between the reporting of external and internal
      measures and training and competition demands. Microsensors, however, may be a
      practical and convenient method of player monitoring in basketball to overcome
      the limitations associated with current approaches while allowing for external
      demands and internal responses to be recorded simultaneously. The triaxial
      accelerometers of microsensors seem well suited for basketball and warrant
      validation to definitively determine their place in the monitoring of basketball
      players. Coaching staff should make use of this technology by tracking individual
      player responses across the annual plan and using real-time monitoring to
      minimize factors such as fatigue and injury risk.

PMID- 28445228
TI  - The Relationship of Core Strength and Activation and Performance on Three
      Functional Movement Screens.
AB  - Johnson, CD, Whitehead, PN, Pletcher, ER, Faherty, MS, Lovalekar, MT, Eagle, SR,
      and Keenan, KA. The relationship of core strength and activation and performance
      on three functional movement screens. J Strength Cond Res 32(4): 1166-1173, 2018
      Current measures of core stability used by clinicians and researchers suffer from
      several shortcomings. Three functional movement screens appear, at face-value, to
      be dependent on the ability to activate and control core musculature. These 3
      screens may present a viable alternative to current measures of core stability.
      Thirty-nine subjects completed a deep squat, trunk stability push-up, and rotary
      stability screen. Scores on the 3 screens were summed to calculate a composite
      score (COMP). During the screens, muscle activity was collected to determine the
      length of time that the bilateral erector spinae, rectus abdominis, external
      oblique, and gluteus medius muscles were active. Strength was assessed for core
      muscles (trunk flexion and extension, trunk rotation, and hip abduction and
      adduction) and accessory muscles (knee flexion and extension and pectoralis
      major). Two ordinal logistic regression equations were calculated with COMP as
      the outcome variable, and: (a) core strength and accessory strength, (b) only
      core strength. The first model was significant in predicting COMP (p = 0.004)
      (Pearson's Chi-Square = 149.132, p = 0.435; Nagelkerke's R-Squared = 0.369). The
      second model was significant in predicting COMP (p = 0.001) (Pearson's Chi-Square
      = 148.837, p = 0.488; Nagelkerke's R-Squared = 0.362). The core muscles were
      found to be active for most screens, with percentages of "time active" for each
      muscle ranging from 54-86%. In conclusion, performance on the 3 screens is
      predicted by core strength, even when accounting for "accessory" strength
      variables. Furthermore, it seems the screens elicit wide-ranging activation of
      core muscles. Although more investigation is needed, these screens, collectively,
      seem to be a good assessment of core strength.

PMID- 28445229
TI  - A Cross-Sectional and Retrospective Cohort Analysis of the Effects of Age on
      Flexibility, Strength Endurance, Lower-Body Power, and Aerobic Fitness in Law
      Enforcement Officers.
AB  - There can be a great age range in cohorts of law enforcement officers. As the
      tasks required of officers generally do not change with advancing age, it is
      important to understand how physical performance in tests that assess job
      specific characteristics may be altered. Retrospective analysis of performance
      test data for 383 officers (362 males, 21 females) was conducted. The tests
      included: sit-and-reach to determine hamstring and lower back flexibility;
      maximal push-up and sit-up repetitions in 60 s to measure muscle endurance;
      vertical jump (VJ) to assess lower-body power; and 2.4 km run to ascertain
      aerobic capacity. Data was stratified by age into 20-29, 30-39, 40-49, and 50-59
      year groups, and analyzed by gender. A one-way ANOVA with Bonferroni post hoc
      calculated differences between the groups. Considering the males, the 40-49 and
      50-59 year groups performed poorer in the VJ, sit-up test, and 2.4 km run
      compared to the 20-29 year group (p <= 0.001-0.045). For the females, the 20-29
      year group were superior to the 30-39 (p = 0.013) and 40-49 (p = 0.025) year
      groups in the push-up test. To ensure an older officer can successfully complete
      occupation-specific tasks, lower-body power, abdominal strength, and aerobic
      training should be completed. Female officers should also attempt to maintain
      relative upper-body strength. Practitioners must attempt to design training
      programs that fit within the context of the occupational demands, as well as
      potentially utilizing a non-traditional training design as law enforcement
      officers may not have the time to follow a traditional periodization model.

PMID- 28445230
TI  - Comparison between Unilateral and Bilateral Plyometric Training on Single and
      Double Leg Jumping Performance and Strength.
AB  - This study compared the effects of unilateral and bilateral plyometric training
      on single and double-leg jumping performance, maximal strength and rate of force
      development (RFD). Fifteen moderately trained subjects were randomly assigned to
      either a unilateral (U, n=7) or bilateral group (B, n=8). Both groups performed
      maximal effort plyometric leg exercises two times per week for 6 weeks. The B
      group performed all exercises with both legs, while the U group performed half
      the repetitions with each leg, so that total exercise volume was the same.
      Jumping performance was assessed by countermovement jumps (CMJ) and drop jumps
      (DJ), while maximal isometric leg press strength and RFD were measured before and
      after training for each leg separately and both legs together. CMJ improvement
      with both legs was not significantly different between U (12.1+/-7.2%) and B
      (11.0+/-5.5%) groups. However, the sum of right and left leg CMJ only improved in
      the U group (19.0+/-7.1%, p<0.001) and was unchanged in the B group (3.4+/-8.4%,
      p=0.80). Maximal isometric leg press force with both legs was increased similarly
      between groups (B: 20.1+/-6.5%, U: 19.9+/-6.2%). However, the sum of right and
      left leg maximal force increased more in U compared to B group (23.8+/-9.1% vs.
      11.9+/-6.2%, p=0.009, respectively). Similarly, the sum of right and left leg
      RFD0-50 and RFD0-100 were improved only in the U group (34-36%, p<0.01).
      Unilateral plyometric training was more effective at increasing both single and
      double-leg jumping performance, isometric leg press maximal force and RFD when
      compared to bilateral training.

PMID- 28445231
TI  - The effects of multi-day vs. Single pre-exercise nitrate supplement dosing on
      simulated cycling time trial performance and skeletal muscle oxygenation.
AB  - A transient augmentation in the metabolic efficiency of skeletal muscle is the
      purported basis for dietary nitrate supplementation amongst competitive and
      recreational athletes alike. Previous studies support the ergogenic effects of
      nitrate supplementation as findings indicated improved microvascular blood flow,
      exercise economy, and performance with relatively short-term supplementation. As
      with most ergogenic aids, the optimum duration of supplementation prior to
      performance or competition, i.e. loading phase, is a critical determinant for
      efficacy. Therefore, the purpose of this study was to investigate the effects of
      long-term vs. single dosing nitrate supplementation on skeletal muscle
      oxygenation and cycling performance. In a randomized, placebo controlled, double
      blind, parallel design study, healthy, recreationally active male (n=15) and
      female (n=14) subjects (age= 18-29 yrs.) completed an 8 km (5mi) simulated
      cycling time trial before and after a 14-day supplementation period with either a
      nitrate supplement (Multi-Day Dosing; MD) (n=14) or placebo (Single Pre-Exercise
      Dosing; SD) (n=15). Both groups consumed a single dose of the nitrate supplement
      2 hours prior to the post-treatment time trial. In addition, skeletal muscle
      oxygenation was measured via near-infrared spectroscopy during each time trial.
      Multi-day nitrate supplementation significantly decreased time to completion
      (TTC) (p=0.01) and increased average power (PWRAVG) (p=0.04) and speed (SPEEDAVG)
      (p=0.02) from pre- to post-treatment while a single dosing produced no
      significant changes to these measures. There were no significant differences over
      time and across treatments for any other measures including muscle oxygenation
      variables. Overall, long-term nitrate supplementation appears to have an
      advantage over a single pre-exercise dosing on cycling performance and metabolic
      efficiency as indicated by an increase in power output with no change in
      oxygenation.

PMID- 28445232
TI  - Organised chaos in late specialisation team sports: Weekly training loads of
      elite adolescent rugby union players.
AB  - The aim of this study was to quantify the mean weekly training load (TL) of elite
      adolescent rugby union players participating in multiple teams, and examine the
      differences between playing positions. Twenty elite male adolescent rugby union
      players (17.4 +/- 0.7 years) were recruited from a regional academy and
      categorised by playing position; forwards (n=10) and backs (n=10). Global
      positioning system and accelerometer microtechnology was used to quantify
      external TL, and session-rating of perceived exertion (sRPE) was used to quantify
      internal TL during all sessions throughout a 10-week in-season period. A total of
      97 complete observations (5 +/- 3 weeks per participant) were analysed, and
      differences between-positions were assessed using Cohen's d effect sizes (ES) and
      magnitude-based inferences. Mean weekly sRPE was 1217 +/- 364 AU (between-subject
      coefficient of variation (CV) = 30%), with a total distance (TD) of 11629 +/-
      3445 m (CV= 30%), and PlayerLoad (PL) of 1124 +/- 330 AU (CV= 29%). Within
      subject CV ranged between 5-78% for sRPE, 24-82% for TD, and 19-84% for PL. Mean
      TD (13063 +/- 3933 vs. 10195 +/- 2242 m), and PL (1246 +/- 345 vs. 1002 +/- 279
      AU) were both likely greater for backs compared to forwards (moderate ES),
      however differences in sRPE were unclear (small ES). Although mean internal TLs
      and volumes were low, external TLs were higher than previously reported during
      pre-season and in-season periods in senior professional players. Additionally,
      the large between-subject and within-subject variation in weekly TL suggests
      players participate in a chaotic training system.

PMID- 28445233
TI  - Preclinical models for translational sarcoma research.
AB  - PURPOSE OF REVIEW: Sarcoma is a basket term for mesenchymal tumors for which more
      than 75 genetically and histologically distinct subtypes are recognized.
      Therapeutic progress has largely been achieved with classical chemotherapeutic
      drugs that were tested in empirical clinical trials. However, outcome in
      metastatic patients remains poor and with few exceptions numerous trials have
      failed or only provided limited improvement in recent years. RECENT FINDINGS:
      Given the genomic heterogeneity, preclinical model systems will be indispensable
      to identify new molecular targets and to prioritize drugs and drug combinations.
      Cell culture is still widely used in preclinical sarcoma research to identify
      potential novel therapeutic approaches and resistance mechanisms. New and
      improved techniques in genome-wide and proteome-wide screens enable a better
      characterization. In addition to cell line xenograft mouse models, patient
      derived xenografts crucially broadened and improved preclinical studies using
      primary human samples. Finally, novel strategies for genome editing, like
      CRISPR/Cas and sleeping beauty transposon, lead to development of novel
      genetically engineered cell lines and mouse models. SUMMARY: The present review
      gives a non-comprehensive overview on current model systems used in sarcoma
      research and discusses their translational relevance. Those include cell lines,
      subtype-specific patient-derived cell lines and xenografts as well as
      developments in genome editing and genetically engineered cell lines and mouse
      models.

PMID- 28445234
TI  - Safe New Approach to the Lingual Flap Management in Mandibular Augmentation
      Procedures: The Digitoclastic Technique.
AB  - PURPOSE: This article describes the digitoclastic technique, an innovative
      procedure for coronal displacement of the lingual flap. The new technique has the
      potential to obtain primary flap closure without surgical risks to the anatomical
      structures on the lingual side of the mandible. MATERIALS AND METHODS:
      Reconstruction of an atrophic mandible with guided tissue regeneration (guided
      bone regeneration) and implant placement is described, using the digitoclastic
      technique to displace the lingual flap coronally. RESULTS: Coronal flap
      displacement was sufficient to obtain complete passive coverage of the grafted
      area. No bleeding or neurosensory complications were recorded, and no membrane
      exposure occurred. CONCLUSIONS: The digitoclastic technique reduces the risk of
      damage to the lingual nerve and minimizes the amount of bleeding during surgery,
      allowing progressive and controlled retraction of the flap until the desired
      detachment is achieved.

PMID- 28445235
TI  - Recent Trends in the Epidemiology of Hepatocellular Carcinoma in Olmsted County,
      Minnesota: A US Population-based Study.
AB  - BACKGROUND/AIM: The epidemiology of hepatocellular carcinoma (HCC) has changed in
      the United States recently. The aim of this study is to evaluate the recent
      trends of HCC epidemiology in Olmsted County, MN. METHODS: Residents aged over 20
      with newly diagnosed HCC were identified using the Rochester Epidemiology Project
      database. Clinical information was compared among patients diagnosed between 2000
      and 2009 (era 1) and 2010 to 2014 (era 2). RESULTS: Over 1.6 million person years
      of follow-up, 93 residents were diagnosed with HCC. The mean age was 67 and 71%
      were male. The age-adjusted and sex-adjusted incidence rates were 6.3 and 7.0 per
      100,000 person years in the first and second eras (P=0.64). The proportion with
      hepatitis B virus etiology increased from 4% to 21% between the 2 eras (P<0.01),
      whereas there was a trend toward a decreasing proportion of hepatitis C virus
      etiology from 42% to 29% (P=0.20). Only 39% of HCC surveillance candidates had
      HCCs detected under surveillance and 41% of cirrhotic patients had unrecognized
      cirrhosis at the time of HCC diagnosis. Nonalcoholic fatty liver disease was
      associated with unrecognized cirrhosis and absence of cirrhosis at HCC diagnosis.
      More than half (56%) of patients presented at Barcelona Clinic Liver Cancer stage
      C or D and the median survival was 9.7 months. The overall survival had not
      changed over time. CONCLUSIONS: The incidence of HCC remained stable after 2010
      in Olmsted County. The proportion of hepatitis B virus-induced HCC increased,
      whereas there was a trend of decreasing proportion of hepatitis C virus-induced
      HCC. The overall survival in community residents with HCC remains poor.

PMID- 28445236
TI  - Risk Stratification in Acute Variceal Bleeding: Child-Pugh Versus Model for End
      stage Liver Disease.

PMID- 28445238
TI  - Hydrogen Sulfide Confers Lung Protection During Mechanical Ventilation via
      Cyclooxygenase 2, 15-deoxy Delta12,14-Prostaglandin J2, and Peroxisome
      Proliferator-Activated Receptor Gamma.
AB  - OBJECTIVES: Hydrogen sulfide reduces ventilator-induced lung injury in mice.
      Here, we have examined the underlying mechanisms of hydrogen sulfide-mediated
      lung protection and determined the involvement of cyclooxygenase 2, 15-deoxy
      Delta-prostaglandin J2, and peroxisome proliferator-activated receptor gamma in
      this response. DESIGN: Randomized, experimental study. SETTING: University
      medical center research laboratory. SUBJECTS: C57BL/6 mice and in vitro cell
      catheters. INTERVENTIONS: The effects of hydrogen sulfide were analyzed in a
      mouse ventilator-induced lung injury model in vivo as well as in a cell stretch
      model in vitro in the absence or presence of hydrogen sulfide. The physiologic
      relevance of our findings was confirmed using pharmacologic inhibitors of
      cyclooxygenase 2 and peroxisome proliferator-activated receptor gamma.
      MEASUREMENTS AND MAIN RESULTS: Mechanical ventilation caused significant lung
      inflammation and injury that was prevented in the presence of hydrogen sulfide.
      Hydrogen sulfide-mediated protection was associated with induction of
      cyclooxygenase 2 and increases of its product 15-deoxy Delta-prostaglandin J2 as
      well as cyclooxygenase 2/15-deoxy Delta-prostaglandin J2-dependent activation of
      peroxisome proliferator-activated receptor gamma. Hydrogen sulfide-dependent
      effects were mainly observed in macrophages. Applied mechanical stretch to RAW
      264.7 macrophages resulted in increased expression of interleukin receptor 1
      messenger RNA and release of macrophage inflammatory protein-2. In contrast,
      incubation of stretched macrophages with sodium hydrosulfide prevented the
      inflammatory response dependent on peroxisome proliferator-activated receptor
      gamma activity. Finally, application of a specific peroxisome proliferator
      activated receptor gamma inhibitor abolished hydrogen sulfide-mediated protection
      in ventilated animals. CONCLUSIONS: One hydrogen sulfide-triggered mechanism in
      the protection against ventilator-induced lung injury involves cyclooxygenase
      2/15-deoxy Delta-prostaglandin J2-dependent activation of peroxisome proliferator
      activated receptor gamma and macrophage activity.

PMID- 28445237
TI  - Effects of Polymyxin B Hemoperfusion on Mortality in Patients With Severe Sepsis
      and Septic Shock: A Systemic Review, Meta-Analysis Update, and Disease Severity
      Subgroup Meta-Analysis.
AB  - OBJECTIVE: Several studies have reported a survival benefit for polymyxin B
      hemoperfusion treatment in patients with severe sepsis and septic shock. However,
      recently, a propensity-matched analysis and a randomized controlled trial
      reported no survival benefit for polymyxin B hemoperfusion treatment. We
      performed an up-to-date meta-analysis to determine the effect of polymyxin B
      hemoperfusion treatment on mortality in patients with severe sepsis and septic
      shock. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched from
      inception to May 2016. STUDY SELECTION: Studies investigating the effect of
      polymyxin B hemoperfusion on mortality were considered eligible. We searched for
      terms related to severe sepsis and septic shock and terms related to polymyxin B
      hemoperfusion. DATA EXTRACTION: The following data were extracted from the
      original articles: the name of the first author and publication year, subjects
      and setting, inclusion and exclusion criteria, mean age and size of the study
      population, male percentage, mortality, blood pressure, Sequential Organ Failure
      Assessment score, pulmonary oxygenation, and levels of endotoxin and humoral
      cytokines. DATA SYNTHESIS: A total of 17 trials were included. The pooled risk
      ratio for overall mortality was 0.81 (95% CI, 0.70-0.95), favoring polymyxin B
      hemoperfusion (p = 0.007). Disease severity subgroup meta-analysis revealed a
      significant reduction of mortality in the intermediate- and high-risk groups
      (risk ratio, 0.84; 95% CI, 0.77-0.92 and risk ratio, 0.64; 95% CI, 0.52-0.78,
      respectively), but not in the low-risk group (risk ratio, 1.278; 95% CI, 0.888
      1.839). The nonlinear meta-regression with restricted cubic spline showed an
      almost linear inverse association between the baseline mortality rate and
      reduction in the risk of mortality. CONCLUSION: The present study demonstrated
      that polymyxin B hemoperfusion treatment may reduce mortality in patients with
      severe sepsis and septic shock in specific disease severity subgroups.

PMID- 28445240
TI  - Evaluation of a Pediatric Early Warning Score Across Different Subspecialty
      Patients.
AB  - OBJECTIVE: To evaluate the ability of a Pediatric Early Warning Score to predict
      deterioration in different subspecialty patient populations. DESIGN: Single
      center, retrospective cohort study. Patients were classified into five groups: 1)
      cardiac; 2) hematology/oncology/bone marrow transplant; 3) surgical; 4)
      neurologic; and 5) general medical. The relationship between the Pediatric Early
      Warning Score and unplanned ICU transfer requiring initiation of specific ICU
      therapies (intubation, high-flow nasal cannula, noninvasive ventilation,
      inotropes, or aggressive fluid hydration within 12 hr of transfer) was evaluated.
      SETTING: Tertiary care, free-standing, academic children's hospital. PATIENTS:
      All hospitalized acute care patients admitted over a 6-month time period
      (September 2012 to March 2013). INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: During the study time period, 33,800 patient-days and 136 deteriorations
      were evaluated. Area under the curve ranged from 0.88 (surgical) to 0.94
      (cardiac). Sensitivities for a Pediatric Early Warning Score greater than or
      equal to 3 ranged from 75% (surgical) to 94% (cardiology) and number needed to
      evaluate to find one deterioration was 11.5 (neurologic) to 43 patients
      (surgical). Sensitivities for a Pediatric Early Warning Score greater than or
      equal to 4 ranged from 54% (general medical) to 79% (hematology/oncology/bone
      marrow transplant) and number needed to evaluate of 5.5 (neurologic) to 12
      patients (general medical). Sensitivities for a Pediatric Early Warning Score of
      greater than or equal to 5 ranged from 25% (surgical) to 58%
      (hematology/oncology/bone marrow transplant) and number needed to evaluate of 3.5
      (cardiac, hematology/oncology/bone marrow transplant, neurologic) to eight
      patients (surgical). CONCLUSIONS: An elevated Pediatric Early Warning Score is
      associated with ICU transfer and receipt of ICU-specific interventions in
      patients across different pediatric subspecialty patient populations.

PMID- 28445239
TI  - Aldosterone and Vascular Mineralocorticoid Receptors in Murine Endotoxic and
      Human Septic Shock.
AB  - OBJECTIVES: Vascular mineralocorticoid receptors play a role in vascular tone and
      blood pressure regulation, might participate in the pathophysiology of
      circulatory failure during sepsis, and represent a potential therapeutic target
      in this disease. We aimed to study the effects of mineralocorticoids and the
      involvement of vascular mineralocorticoid receptors in murine endotoxic and human
      septic shock. DESIGN: Experimental study. SETTING: Translational investigation
      including animal research and in vitro experiments using human vascular cells and
      plasma from septic patients. SUBJECTS: Adult male C57Black 6 mice, adult patients
      with septic shock. INTERVENTIONS: Mice were injected with lipopolysaccharide
      and/or aldosterone. Human endothelial and smooth muscle cells were treated with
      pro-inflammatory cytokines with or without aldosterone, nuclear factor-kappaB
      inhibitor BAY 11-7082, or plasma from septic patients. MEASUREMENTS AND MAIN
      RESULTS: Aldosterone improved 5-day survival, invasive arterial pressure, and in
      vivo and ex vivo arterial response to phenylephrine at 18 hours after induction
      of murine endotoxic shock. Both alpha1-adrenoceptor and mineralocorticoid
      receptor expressions studied in mouse aortas were down-regulated at 6 and 18
      hours in endotoxemic mice and restored in aldosterone-treated mice. Furthermore,
      tumor necrosis factor-alpha decreased both mineralocorticoid receptor and alpha1
      adrenoceptor expressions within 5 hours in human vascular cells in a nuclear
      factor-kappaB pathway-dependent manner. Mineralocorticoid receptor expression was
      also blunted in human cells treated with plasma from septic patients. CONCLUSION:
      We found a beneficial effect of mineralocorticoids on survival, blood pressure,
      and vascular reactivity, associated with a restoration of alpha1-adrenoceptor
      expression in endotoxic shock. Furthermore, blunted vascular mineralocorticoid
      receptor expression might participate in hemodynamic failure during sepsis.

PMID- 28445241
TI  - Serum Neutrophil Gelatinase-Associated Lipocalin: A Diagnostic Marker in
      Pediatric Sepsis.
AB  - OBJECTIVES: Sepsis is a life-threatening condition that arises when the response
      of the body to infection injures its own tissues and organs. The early prediction
      of sepsis by current clinical and laboratory methods remains inadequate. Serum
      neutrophil gelatinase-associated lipocalin level is increased in sepsis
      irrespective of renal dysfunction. Therefore, we aimed to correlate the serum
      neutrophil gelatinase-associated lipocalin value determined at admission with
      clinical progression and severity of disease in critically ill children and to
      declare its role as a potential diagnostic and prognostic marker for sepsis in
      critically ill children in the emergency department. DESIGN: A prospective cohort
      study. SETTING: The study carried out at the PICU of Menoufia University
      Hospital. PATIENTS: We serially enrolled 120 critically ill children admitted to
      the PICU at 2 fixed days per week in addition to 40 healthy children served as
      controls. INTERVENTIONS: Clinical examination was performed including calculation
      of the Pediatric Risk of Mortality and Pediatric Index of Mortality 2. Serum
      neutrophil gelatinase-associated lipocalin measurement was performed for patients
      at admission and for the controls. Patients were followed up for 30 days. The
      discriminatory power of neutrophil gelatinase- associated lipocalin was
      determined using the receiver-operating characteristic and other predictive
      likelihood values. MEASUREMENTS AND MAIN RESULTS: Serum neutrophil gelatinase
      associated lipocalin level was significantly higher among the total patient
      cohort and those with sepsis than among the controls (p < 0.001), also in
      patients with systemic inflammatory response syndrome without sepsis and patients
      without systemic inflammatory response syndrome (p = 0.04 and <0.001).
      Furthermore, plasma level of neutrophil gelatinase-associated lipocalin was
      significantly elevated in nonsurvivors compared with survivors (p < 0. 001).
      Receiver-operating characteristic curve analysis exhibited an area under the
      curve of 0.84 for neutrophil gelatinase-associated lipocalin for diagnosis of
      sepsis, whereas C-reactive protein had an area under the curve of 0.79. Regarding
      the prognosis, neutrophil gelatinase-associated lipocalin had an area under the
      curve of 0.74 for prediction of mortality, whereas the area under the curve for
      Pediatric Risk of Mortality, Pediatric Index of Mortality 2, and C-reactive
      protein were 0.59, 0.58, and 0.62, respectively. CONCLUSION: Overall, the data
      support the view that measurement at admission, serum neutrophil gelatinase
      associated lipocalin results in substantial added value for early diagnosis and
      prognostication of sepsis in critically sick children.

PMID- 28445242
TI  - Increased Mortality and Length of Stay Associated With Medical Emergency Team
      Review in Hospitalized Pediatric Patients: A Retrospective Cohort Study.
AB  - OBJECTIVE: Rapid response systems using medical emergency teams reduce hospital
      wide cardiorespiratory arrest and mortality. While rapid response systems improve
      hospital-wide outcomes, children receiving medical emergency team review may
      still be at increased risk for morbidity and mortality. The study purpose was to
      compare the length of stay and mortality rate in children receiving a medical
      emergency team review with those of other hospitalized children. DESIGN:
      Retrospective cohort study. SETTING: Tertiary Pediatric Hospital, Children's
      Hospital of Eastern Ontario, Ottawa, Canada. PATIENTS: Cohort of 42,308 pediatric
      admissions to the general inpatient ward. INTERVENTIONS: Data over 7 years were
      obtained from a prospectively maintained rapid response systems database.
      MEASUREMENTS AND MAIN RESULTS: From the cohort, 995 (2.35%) of the admissions had
      one and 276 (0.65%) had multiple medical emergency team activations. When
      compared with patients without, children having one or multiple medical emergency
      team reviews had 13.34 (95% CI, 5.33-33.2) and 50.10 (95% CI, 19.86-126.39) times
      the odds of death, respectively. Patients experiencing a medical emergency team
      review stayed in hospital 1.59 times (95% CI, 1.39-1.82) longer, whereas those
      with multiple medical emergency team reviews stayed 2.44 times (95% CI, 1.85
      3.20) longer. The associations remained significant after controlling for
      important confounders and excluding elective admissions from the analyses. Most
      repeat medical emergency team reviews occurred within a day of the initial review
      or involved patients with multiple comorbidities. CONCLUSIONS: Our study suggests
      that pediatric patients reviewed by the medical emergency team are at
      significantly higher risk of mortality and longer length of stay than general
      ward inpatients. As well, patients with multiple medical emergency team reviews
      were at particularly high risk compared with patients with one medical emergency
      team review. Patients who experience medical emergency team reviews should be
      recognized as a high-risk group, and future studies should consider how to
      decrease morbidity and mortality. Based on our findings, we suggest that these
      patients be followed for 24-48 hours after any medical emergency team activation.

PMID- 28445243
TI  - Harmonizing standardized uptake value recovery between two PET/CT systems from
      different manufacturers when using resolution modelling and time-of-flight.
AB  - PET iterative reconstruction algorithms with resolution modelling (RM) can be
      used to improve spatial resolution in the images. However, RM has a significant
      impact on quantification, which raises issues for harmonization across
      multicentre networks or collaborations. This investigation compared
      quantification from two modern time-of-flight (TOF) PET/CT systems from different
      manufacturers with RM with the intention to harmonize recovery. Images of a
      National Electrical Manufacturers Association image quality phantom with a sphere
      to-background concentration ratio of 4 : 1 were acquired on a GE Discovery 710
      and a Siemens Biograph mCT and reconstructed with RM and TOF. Voxel dimensions
      and image noise (background coefficient of variation) were matched. One to five
      iterations were used with 2 and 4 mm Gaussian filters. Mean and maximum contrast
      recovery (CR) were measured for the 10, 13, 17 and 22 mm hot phantom spheres.
      Notable differences in CR for images reconstructed with matched reconstruction
      parameters were observed between the scanners. A set of parameters was found that
      reduced differences in CR between scanners. Using these parameters, relative
      differences for the Biograph compared with the Discovery were -8.1, -3.7, +7 and
      +0.7% for mean CR and -23.1, -6.9, +9.1 and +0.9% for maximum CR in the 10, 13,
      17 and 22 mm spheres, respectively. This study has used a technique of
      harmonizing standardized uptake value recovery on PET/CT systems from different
      vendors with advanced reconstructions including TOF and RM using phantom data.
      Considerable quantitative differences may occur in images, which highlights the
      need to apply methods such as those used in this work for multicentre studies.

PMID- 28445244
TI  - Outcomes After Primary Infliximab Treatment Failure in Inflammatory Bowel
      Disease.
AB  - BACKGROUND: Primary infliximab treatment failure is common in patients with
      inflammatory bowel disease and represents a challenge to clinicians. Treatment
      options are limited. This study assessed the prognosis, defined as surgery-free
      survival, in patients with primary infliximab treatment failure as compared to
      patients without primary failure (initial responders). Furthermore, this study
      assessed the specter of medical therapies used after primary infliximab treatment
      failure along with treatment outcomes. METHODS: Retrospective, observational,
      cohort study of patients with inflammatory bowel disease treated with infliximab
      as first-line anti-tumor necrosis factor treatment at a tertiary center. Primary
      infliximab treatment failure was defined as no clinical improvement during
      infliximab induction therapy resulting in discontinuation of infliximab therapy.
      RESULTS: A total of 560 patients (Crohn's disease n = 353 and ulcerative colitis
      n = 207) were treated with infliximab. Among these, 81 (15%) had primary
      infliximab treatment failure after a median of 3 infusions (weeks 0, 2, and 6)
      (interquartile range 2-4). The median surgery-free survival was 196 days from
      first infusion. One year after primary infliximab treatment failure, the majority
      of patients (n = 51, 63%) had inflammatory bowel disease-related surgery (Crohn's
      disease n = 19, 58%; ulcerative colitis n = 32, 67%; P = 0.49). There was a
      markedly increased risk of surgery in patients with primary infliximab treatment
      failure as compared to initial responders: odds ratio 6.3 (3.8-10.6), P < 0.0001.
      Among 30 patients handled by medical therapies, 16 (53%) still had active disease
      1 year after primary infliximab treatment failure. CONCLUSIONS: Primary
      infliximab treatment failure is associated with poor outcome including high risk
      of surgery or sustained active disease despite medical interventions.

PMID- 28445245
TI  - Ectopic Expression of Innate Immune Protein, Lipocalin-2, in Lactococcus lactis
      Protects Against Gut and Environmental Stressors.
AB  - BACKGROUND: Lipocalin-2 (Lcn2) is a multifunctional innate immune protein that
      exhibits antimicrobial activity by the sequestration of bacterial siderophores,
      regulates iron homeostasis, and augments cellular tolerance to oxidative stress.
      Studies in the murine model of colitis have demonstrated that Lcn2 deficiency
      exacerbates colitogenesis; however, the therapeutic potential of Lcn2
      supplementation has yet to be elucidated. In light of its potential
      mucoprotective functions, we, herein, investigated whether expression of Lcn2 in
      the probiotic bacterium can be exploited to alleviate experimental colitis.
      METHODS: Murine Lcn2 was cloned into the pT1NX plasmid and transformed into
      Lactococcus lactis to generate L. lactis-expressing Lcn2 (Lactis-Lcn2) or the
      empty plasmid (Lactis-Con). Lactis-Lcn2 was characterized by immunoblot and
      enzyme-linked immunosorbent assay and tested for its antimicrobial efficacy on
      Escherichia coli. The capacity of Lactis-Lcn2 and Lactis-Con to withstand adverse
      conditions was tested using in vitro viability assays. Dextran sodium sulfate
      colitis model was used to investigate the colonization ability and therapeutic
      potential of Lactis-Lcn2 and Lactis-Con. RESULTS: Lcn2 derived from Lactis-Lcn2
      inhibited the growth of E. coli and reduced the bioactivity of enterobactin (E.
      coli-derived siderophore) in vitro. Lactis-Lcn2 displayed enhanced tolerance to
      adverse pH, high concentration of bile acids, and oxidative stress in vitro and
      survived better in the inflamed gut than Lactis-Con. Consistent with these
      features, Lactis-Lcn2 displayed better mucoprotection against intestinal
      inflammation than Lactis-Con when administered into mice with dextran sulfate
      sodium-induced acute colitis. CONCLUSIONS: Our findings suggest that Lcn2
      expression can be exploited to enhance the survivability of probiotic bacteria
      during inflammation, which could further improve its efficacy to treat
      experimental colitis.

PMID- 28445247
TI  - The Mucosal Antibacterial Response Profile and Fecal Microbiota Composition Are
      Linked to the Disease Course in Patients with Newly Diagnosed Ulcerative Colitis.
AB  - BACKGROUND: The clinical disease course of ulcerative colitis (UC) varies
      substantially between individuals and can currently not be reliably predicted.
      The gut microbiota and the host's immune defense are key players for gut
      homeostasis and may be linked to disease outcome. The aim of this study was to
      determine fecal microbiota composition and mucosal antibacterial response profile
      in untreated patients with newly diagnosed UC and the impact of these factors on
      disease course. METHODS: Stool samples and intestinal biopsies were obtained from
      therapy-naive newly diagnosed patients with UC. Patients were defined to have
      mild or moderate/severe disease course assessed by disease activity during the 3
      years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n =
      18), and gene expression in intestinal biopsies was analyzed by RT Profiler
      polymerase chain reaction array (n = 13) and real-time polymerase chain reaction
      (n = 44). RESULTS: At the time of diagnosis of UC, the fecal microbiota
      composition discriminated between patients with mild versus moderate/severe
      disease course. Also, the mucosal antibacterial gene expression response profile
      differed between patients with mild versus moderate/severe disease course with
      bactericidal/permeability-increasing protein (BPI) being most important for the
      discrimination. Mucosal bactericidal/permeability-increasing protein gene
      expression at diagnosis was higher in patients with mild versus moderate/severe
      disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and
      was a good predictor for the number of flares during the 3 years follow-up (R =
      0.395, P < 0.0001). CONCLUSIONS: In patients with newly diagnosed UC, fecal
      microbiota composition and mucosal antibacterial response profile, especially
      bactericidal/permeability-increasing protein, are linked to disease course.

PMID- 28445246
TI  - Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is
      Safe and Effective in Increasing Microbial Diversity in Active Ulcerative
      Colitis.
AB  - BACKGROUND: Recent trials suggest fecal microbiota transplantation (FMT) with
      repeated enemas and high-diversity FMT donors is a promising treatment to induce
      remission in ulcerative colitis. METHODS: We designed a prospective, open-label
      pilot study to assess the safety, clinical efficacy, and microbial engraftment of
      single FMT delivery by colonoscopy for active ulcerative colitis using a 2-donor
      fecal microbiota preparation (FMP). Safety and clinical endpoints of response,
      remission, and mucosal healing at week 4 were assessed. Fecal DNA and rectal
      biopsies were used to characterize the microbiome and mucosal CD4 T cells,
      respectively, before and after FMT. RESULTS: Of the 20 patients enrolled in this
      study, 7 patients (35%) achieved a clinical response by week 4. Three patients
      (15%) were in remission at week 4 and 2 of these patients (10%) achieved mucosal
      healing. Three patients (15%) required escalation of care. No serious adverse
      events were observed. Microbiome analysis revealed that restricted diversity of
      recipients pre-FMT was significantly increased by high-diversity 2-donor FMP. The
      microbiome of recipients post-transplant was more similar to the donor FMP than
      the pretransplant recipient sample in both responders and nonresponders. Notably,
      donor composition correlated with clinical response. Mucosal CD4 T-cell analysis
      revealed a reduction in both Th1 and regulatory T-cells post-FMT. CONCLUSIONS:
      High-diversity, 2-donor FMP delivery by colonoscopy seems safe and effective in
      increasing fecal microbial diversity in patients with active ulcerative colitis.
      Donor composition correlated with clinical response and further characterization
      of immunological parameters may provide insight into factors influencing clinical
      outcome.

PMID- 28445248
TI  - Declining US Life Expectancy: A First Look.

PMID- 28445249
TI  - Study on the mechanisms of seizure-like events suppression effect by electrical
      stimulation using a microelectrode array.
AB  - In this paper, we studied the mechanisms underlying the suppression of seizure
      like events (SLEs) by electrical stimulation. We conducted an in-vitro experiment
      using entorhinal cortex combined hippocampal slices and two convulsant drugs,
      bicuculline and 4-aminopyridine, to induce spontaneous SLEs. We used a
      microelectrode array to observe network dynamics over the entire hippocampal area
      simultaneously, including regions far from the stimulation site. We stimulated
      the entorhinal cortex region, which has been determined to be a focus of SLEs by
      Granger causality analysis of multichannel time series data, by an external
      electrode. In bicuculline application, electrical stimulation showed a marked
      suppression effect, even though the sizes of the effective region differed. In 4
      aminopyridine application, however, stimulation under the same conditions did not
      suppress the activities in ~80% of SLEs. The suppression effect was more
      remarkable in the areas surrounding the stimulation site in both cases. Our
      experimental results could support the neuronal depolarization blockade mechanism
      by accumulation of extracellular potassium ions, which is one of the most
      convincing mechanisms to understand seizure suppression phenomena because of
      electrical stimulation. Computer simulation using a neuronal network model also
      confirmed the mechanism.

PMID- 28445250
TI  - Enteric Fever in Children in Western Sydney, Australia, 2003-2015.
AB  - BACKGROUND: Enteric fever is a vaccine-preventable disease with cases in
      Australia predominantly acquired overseas. The aim of this study was to define
      the burden of enteric fever in children presenting to a pediatric hospital in
      Western Sydney between 2003 and 2015. METHODS: Cases between January 2003 and
      December 2013 were ascertained through medical records using International
      Classification of Disease-coded discharge diagnoses, cross-referenced with
      microbiology laboratory data for all isolates of Salmonella enterica serovar
      typhi and S. enterica serovar paratyphi. Prospective cases from January 2014 to
      April 2015 were additionally captured through records maintained by the
      infectious diseases team. RESULTS: Seventy-one cases of enteric fever were
      identified in 12.3 years with an average of 4 cases per year between 2003 and
      2008 and 7 cases per year between 2009 and 2014. Two were visitors to Australia,
      8 were recent migrants, and 59 were Australian residents returning from overseas
      travel. Two children had no history of overseas travel. Countries of travel
      predominantly included the Indian subcontinent (60/69) and Southeast Asia (7/69).
      Of 30 children with information available on pretravel medical consultation, 1
      was offered and received typhoid vaccine. Ninety-four percent of children (67)
      required admission for 1-28 days (median: 5 days). Three children required
      readmission, with 1 case of presumed relapse. Ninety percent (64) were diagnosed
      by blood or stool culture with S. enterica serovar typhi the predominant organism
      (54/64). CONCLUSIONS: In Australia, hospitalizations for pediatric enteric fever
      appear to be increasing; predominantly occurring in Australian-resident children.
      Greater awareness and education are required for parents and clinicians regarding
      travel health risks and prevention strategies.

PMID- 28445251
TI  - Long-term follow-up of patients with chronic hepatitis C treated with alpha
      interferon and ribavirin antiviral therapy: clinical and fibrosis impact of
      treatment response.
AB  - BACKGROUND AND GOALS: The slow progression of chronic hepatitis C (CHC) infection
      requires long observation periods to detect clinical changes. We compare the
      incidence of clinical events, hepatocellular carcinoma (HCC), overall mortality,
      liver-related mortality, and fibrosis progression between patients with a
      sustained virological response (SVR) and nonresponders (NR) after a 13-year
      follow-up period. STUDY: One hundred and eighty-two CHC patients, who received
      interferon and ribavirin treatment between 1996 and 2000, were included. Clinical
      events were evaluated during follow-up. At the end of follow-up, transient
      elastography was used to assess fibrosis progression. RESULTS: Of the 182
      patients, 46.7% (n=85) achieved an SVR. Twenty-seven patients developed hepatic
      decompensation (one SVR) and 15 developed HCC (three SVR). Twenty-nine patients
      died (eight SVR). Twelve of the 29 deaths were liver related (two SVR).
      Independent factors associated with hepatic decompensation were NR to treatment
      [hazard ratio (HR)=23.35; 95% confidence interval (CI): 2.90-189.25; P=0.003],
      advanced fibrosis at baseline (HR=9.11; 95% CI: 4.13-20.09), and treatment delay
      after diagnosis (HR=1.02; 95% CI: 1.00-1.03; P=0.012). Only the latter two were
      associated with HCC development and liver-related mortality. An assessment of
      liver fibrosis was performed on 125 patients (66 SVR). Fibrosis values were
      significantly lower in SVR patients, showing less progression to advanced stages
      of fibrosis [SVR: 6.6 (2.8); 95% CI: 5.8-7.3] than NR [NR: 14.0 (11.1); 95% CI:
      11.1-16.9; P<0.001]. CONCLUSION: In patients with CHC, SVR is durable and reduces
      clinical events. The risk of HCC development is lower, but not eliminated.
      Sustained responders showed fibrosis stabilization or improved fibrosis values.

PMID- 28445252
TI  - Irreversible electroporation in primary and metastatic hepatic malignancies: A
      review.
AB  - BACKGROUND: Liver cancer makes up a huge percentage of cancer mortality
      worldwide. Irreversible electroporation (IRE) is a relatively new minimally
      invasive nonthermal ablation technique for tumors that applies short pulses of
      high frequency electrical energy to irreversibly destabilize cell membrane to
      induce tumor cell apoptosis. METHODS: This review aims to investigate the studies
      regarding the use of IRE treatment in liver tumors and metastases to liver. We
      searched PubMed for all of IRE relevant English language articles published up to
      September 2016. They included clinical trials, experimental studies,
      observational studies, and reviews. This review manuscript is nothing with ethics
      issues and ethical approval is not provided. RESULTS: In recent years,
      increasingly more studies in both preclinical and clinical settings have been
      conducted to examine the safety and efficacy of this new technique, shedding
      light on the crucial advantages and disadvantages that IRE possesses. Unlike the
      current leading thermal ablation techniques, such as radiofrequency ablation
      (RFA), microwave ablation (MWA), and cryoablation, IRE requires shorter ablation
      time without damaging adjacent important vital structures. CONCLUSION: Although
      IRE has successfully claimed its valuable status in the field of hepatic cancer
      treatment both preclinical and clinical settings. In order to systemically test
      and establish its safety and efficacy for clinical applications, more studies
      still need to be conducted.

PMID- 28445253
TI  - micro-RNA screening and prediction model construction for diagnosis of salt
      sensitive essential hypertension.
AB  - Commonly used tests for diagnosis of salt-sensitive hypertension (SSH) are
      complex and time-consuming, so new methods are required. Many studies have
      demonstrated roles for miRNAs in hypertension; however, the diagnostic value of
      miRNAs has yet to be determined for human SSH. In this study, we examined miRNA
      expression profiles by initial high-throughput miRNA sequencing of samples from
      patients with salt-sensitive and salt-resistant hypertension (SSH and SRH,
      respectively; n = 6, both groups), followed by validation by quantitative real
      time polymerase chain reaction (qRT-PCR) in a larger cohort (n = 91). We also
      evaluated differences in baseline characteristics (e.g., age, sex, body mass
      index, consumption of specific foods) between the SSH and SRH groups. Of 36
      miRNAs identified as differentially expressed between SSH and SRH groups by RNA
      Seq, 8 were analyzed by qRT-PCR. There were significant differences in the
      expression levels of hsa-miR-361-5p and hsa-miR-362-5p between the 2 groups (P =
      .023 and.049, respectively). In addition, there were significant differences in
      sauce and poultry consumption between the 2 groups (P = .004 and.001,
      respectively). The areas under the curve (AUC) determined by receptor operating
      characteristic (ROC) analysis for hsa-miR-361-5p and all 8 miRNAs were 0.793 (95%
      CI, 0.698-0.888; sensitivity = 73.9%, specificity = 74.4%; P < .001) and 0.836
      (95% CI, 0.749-0.922; sensitivity = 80.4%, specificity = 81.4%; P < .001),
      respectively, when sauce and poultry consumption were included in the models.
      Assay feasibility and economic considerations make hsa-miR-361-5p combined with
      the dietary factors the preferred markers for diagnosis of SSH.

PMID- 28445254
TI  - The clinical features, treatment, and prognosis of primary mediastinal malignant
      melanoma: A case report.
AB  - RATIONALE: Primary malignant melanoma (MM) of the mediastinum is exceedingly
      rare; a review of the English-language literature reveals only a small number of
      case reports. In this paper, we discuss a case of primary mediastinal MM and
      present a review of the relevant literature on its clinical features and
      treatment. PATIENT CONCERNS: A 52-year-old male presenting with back pain was
      admitted to our hospital for treatment. Imaging examination revealed an anterior
      mediastinal mass and no evidence of other metastatic or primary lesions.
      DIAGNOSES: After complete resection by video-assisted thoracoscopic surgery
      (VATS), histopathologic examination showed evidence of brown melanin pigment in
      the tumor cells, which were immunohistochemically positive for antimelanoma
      antibodies (HMB-45, Melan-A, S-100, and Ki67). INTERVENTIONS: Given the diagnosis
      of MM after surgery, the tumor was tested for the mutation in the BRAF gene
      (which encodes the serine/threonine-protein kinase B-raf) that leads to a V600E
      amino acid substitution, and the tumor was found to be wild type. Then the
      patient has been given immunotherapy. OUTCOMES: The patient completed 4 cycles of
      immunotherapy, and no recurrence or metastasis has been detected to date.
      LESSONS: In such cases, it is difficult to prove the primary nature of the
      intrathoracic melanoma. Moreover, preoperative identification of this disease is
      challenging, making misdiagnosis likely. Due to fast progression and poor
      prognosis, timely and effective systemic treatment is necessary to improve the
      outcomes for patients with primary mediastinal MM.

PMID- 28445255
TI  - Peutz-Jeghers syndrome with intermittent upper intestinal obstruction: A case
      report and review of the literature.
AB  - RATIONALE: Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic syndrome
      characterized by a unique type of gastrointestinal hamartomatous polyp associated
      with oral and anal mucocutaneous pigmentations. Peutz-Jeghers polyps occur most
      numerously in the small intestine but frequently in the colon and stomach, only a
      few cases have been reported in the duodenum. PATIENT CONCERN: A further family
      history survey discovered 10 out of 14 members of the family (in 4 generations)
      had mucocutaneous pigmentations, but many of them were living in rural areas
      where they had no access to specialized medical services, so none were checked
      with endoscopy for polyps of hamartoma. DIAGNOSES: We report the case of a boy
      patient with mucocutaneous pigmentations over the lips, and a history of
      recurrent bouts of vomit and anemia over the preceding two years, no abdominal
      pain and mass. An upper gastrointestinal endoscopy revealed some small polyps in
      the stomach and multiple sessile polyps in the second part of the duodenum, but
      colonoscopy exam did not reveal any lesion. INTERVENTIONS: A double polypectomy
      and duodenum segmentary resection with end-to-end anastomosis was performed.
      Histopathology of the resected duodenum polyps indicated it to be a typical
      hamartomatous polyp. OUTCOMES: The child was under regular follow-up and
      recovered well. LESSONS: In this case, the patient was characteristic with
      pigmentations on his lips and intermittent upper intestinal obstruction (due to
      mass duodenal polyps), there are no definitive guidelines for the treatment to
      duodenal PJS hamartomatous polyp, each case requires tailor-made management.

PMID- 28445256
TI  - Cost-effectiveness analysis of ultrasonography screening for nonalcoholic fatty
      liver disease in metabolic syndrome patients.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) can be diagnosed early by
      noninvasive ultrasonography; however, the cost-effectiveness of ultrasonography
      screening with intensive weight reduction program in metabolic syndrome patients
      is not clear. This study aims to estimate economic and clinical outcomes of
      ultrasonography in Thailand. METHODS: Cost-effectiveness analysis used decision
      tree and Markov models to estimate lifetime costs and health benefits from
      societal perspective, based on a cohort of 509 metabolic syndrome patients in
      Thailand. Data were obtained from published literatures and Thai database.
      Results were reported as incremental cost-effectiveness ratios (ICERs) in 2014 US
      dollars (USD) per quality-adjusted life year (QALY) gained with discount rate of
      3%. Sensitivity analyses were performed to assess the influence of parameter
      uncertainty on the results. RESULTS: The ICER of ultrasonography screening of 50
      year-old metabolic syndrome patients with intensive weight reduction program was
      958 USD/QALY gained when compared with no screening. The probability of being
      cost-effective was 67% using willingness-to-pay threshold in Thailand (4848
      USD/QALY gained). Screening before 45 years was cost saving while screening at 45
      to 64 years was cost-effective. CONCLUSIONS: For patients with metabolic
      syndromes, ultrasonography screening for NAFLD with intensive weight reduction
      program is a cost-effective program in Thailand. Study can be used as part of
      evidence-informed decision making. TRANSLATIONAL IMPACTS: Findings could
      contribute to changes of NAFLD diagnosis practice in settings where economic
      evidence is used as part of decision-making process. Furthermore, study design,
      model structure, and input parameters could also be used for future research
      addressing similar questions.

PMID- 28445257
TI  - Do inflammatory markers predict prognosis in patients with synchronous colorectal
      cancer?
AB  - Systematic inflammatory response markers are considered as the most informative
      prognostic factors in many types of cancer. However, in synchronous colorectal
      cancer (synCRC), the prognostic value of inflammatory markers, including
      prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), derived
      neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR), and
      lymphocyte-to-monocyte ratio (LMR), had rarely been evaluated. Thus, this present
      study reviewed our consecutive patients with synCRC to investigate the prognostic
      value of those factors.The primary endpoint was overall survival (OS), and
      disease-free survival (DFS) was considered as the secondary endpoint. Receiver
      operating characteristic curve analysis was conducted to determine optimal cutoff
      levels for the 5 markers. Kaplan-Meier survival curves and Cox proportional
      hazards models were applied to assess the relationship between OS, DFS, and
      inflammatory markers.In total, 114 patients with pathologically confirmed synCRC
      at initial diagnosis were identified among 5742 patients who underwent surgery
      for colorectal cancer from October 2009 to May 2013. In the multivariate
      analysis, elevated postoperative NLR (>=10.50) was confirmed as an independent
      prognostic factor for 3-year OS (P = .001; hazard ratio [HR] 4.123, 95%
      confidence interval [CI] 1.750-9.567) and DFS (P = .001; HR 3.342, 95% CI 1.619
      6.898). In addition, for 3-year OS, both tumor grade and pN stage were confirmed
      as independent prognostic factors. And pN stage was confirmed as an independent
      prognostic factor for 3-year DFS.In conclusion, this study identified elevated
      postoperative NLR is associated with a poor prognosis in patients with synCRC
      underwent surgery resection, and the NLR provides improved accuracy for
      predicting clinical outcomes to stratify patients into different risk categories.

PMID- 28445258
TI  - Renal vascular calcification and response to renal nerve denervation in resistant
      hypertension.
AB  - Renal sympathetic nerve denervation (RDN) is accepted as a treatment option for
      patients with resistant hypertension. However, results on decline in ambulatory
      blood pressure (BP) measurement (ABPM) are conflicting. The high rate of
      nonresponders may be related to increased systemic vascular stiffness rather than
      sympathetic overdrive. A single center, prospective registry including 26
      patients with treatment resistant hypertension who underwent RDN at the Isala
      Hospital in the Netherlands. Renal perivascular calcium scores were obtained from
      noncontrast computed tomography scans. Patients were divided into 3 groups based
      on their calcium scores (group I: low 0-50, group II: intermediate 50-1000, and
      group III: high >1000). The primary end point was change in 24-hour ABPM at 6
      months follow-up post-RDN compared to baseline. Seven patients had low calcium
      scores (group I), 13 patients intermediate (group II), and 6 patients had high
      calcium scores (group III). The groups differed significantly at baseline in age
      and baseline diastolic 24-hour ABPM. At 6-month follow-up, no difference in 24
      hour systolic ABPM response was observed between the 3 groups; a systolic ABPM
      decline of respectively -9 +/- 12, -6 +/- 12, -12 +/- 10 mm Hg was found. Also
      the decline in diastolic ambulatory and office systolic and diastolic BP was not
      significantly different between the 3 groups at follow-up. Our preliminary data
      showed that the extent of renal perivascular calcification is not associated with
      the ABPM response to RDN in patients with resistant hypertension.

PMID- 28445259
TI  - The role of STAT3 and AhR in the differentiation of CD4+ T cells into Th17 and
      Treg cells.
AB  - BACKGROUND: This study aimed to investigate the role of aryl hydrocarbon receptor
      (AhR) and STAT3 gene during the differentiation of cluster of differentiation
      (CD)4 T cells into T helper (Th)17 and T regulatory (Treg) cells. METHODS: First,
      CD4 T cells were isolated from the spleen of BALB/c mice. Then, stable CD4 T
      cells expressing STAT3 shRNA were constructed. CD4 T cells were assigned to one
      of the following treatments: Th17 group: antibodies against CD3 and CD28, 2.5
      ng/mL transforming growth factor beta (TGF-beta)1, 30 ng/mL interleukin (IL)-6,
      and 30 ng/mL IL-23; 6-formylindolo[3,2-b]carbazole (FICZ) group: antibodies
      against CD3 and CD28, 2.5 ng/mL TGF-beta1, 30 ng/mL IL-6, 30 ng/mL IL-23, and 100
      nM FICZ; FICZ + STAT3 RNAi group (shSTAT3 group): antibodies against CD3 and
      CD28, 2.5 ng/mL TGF-beta1, 30 ng/mL IL-6, 30 ng/mL IL-23, 100 nM FICZ, and STAT3
      RNAi; naphthoflavone group: antibodies against CD3 and CD28, 2.5 ng/mL TGF-beta1,
      30 ng/mL IL-6, 30 ng/mL IL-23, and 3 MUM naphthoflavone; 5) no antibodies were
      added in the control group. Later, the proportions of Th17 and Treg cells in each
      group were measured by flow cytometry; phospho-STAT3 and -STAT5 levels were
      measured by western blotting; and AhR, STAT3, STAT5, receptor-related orphan
      nuclear receptor gammat (RORgammat), FOXP3, T-cell receptor (TCR), CD25, IL-6R,
      IL-10, and IL-17 mRNA levels were also measured by real-time PCR. RESULT: Th17
      cells showed a rise and Treg cells showed a decrease in the FICZ group, but
      revised in the shSTAT3 group and the naphthoflavone group. Significant
      differences were observed in CD25, IL-6R, IL-10, and IL-17 mRNA levels among
      different groups. CONCLUSION: STAT3 may cooperate with AhR to regulate the
      differentiation of both Th17 and Treg cells.

PMID- 28445260
TI  - Association of CagA EPIYA-D or EPIYA-C phosphorylation sites with peptic ulcer
      and gastric cancer risks: A meta-analysis.
AB  - BACKGROUND: Increasingly, studies have focused on the relationship between
      Helicobacter pylori (H pylori) cytotoxin associated gene A protein (CagA) Glu-Pro
      Ile-Tyr-Ala (EPIYA)-D motifs or multiple EPIYA-C phosphorylation sites and peptic
      ulcer disease (PUD) or gastric cancer (GC) risk. However, the conclusions have
      been inconsistent. The aim of this meta-analysis was to evaluate whether 1 CagA
      EPIYA-D motif or multiple EPIYA-C phosphorylation sites were associated with PUD
      or GC risk. MATERIALS AND METHODS: A literature search was performed in PubMed,
      Web of Science, Wanfang Data, Excerpt Medica Database, and the Chinese National
      Knowledge Infrastructure database to identify eligible research. We analyzed the
      odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of
      association. RESULTS: Compared with 1 EPIYA-C motif in Asian populations, 1 EPIYA
      D site was associated with an increased GC risk (OR=1.91, 95% CI=1.19-3.07, P =
      .008). However, 1 EPIYA-D motif was not significantly associated with PUD (OR =
      0.90, 95% CI = 0.46-1.76, P = .764), gastric ulcer (GU) (OR = 0.85, 95% CI = 0.27
      2.63, P = .771), or duodenal ulcer (DU) (OR = 0.89, 95% CI = 0.25-3.16, P = .859)
      risk. Compared with no more than 1 EPIYA-C motif, multiple motifs were associated
      with increased PUD (OR = 2.33, 95% CI = 1.29-4.20, P = .005) and DU (OR = 2.32,
      95% CI = 1.08-5.00, P = .031) risk in Asia and GC risk in the United States and
      Europe (OR = 3.28, 95% CI = 2.32-4.64, P < .001). Multiple EPIYA-C sites were not
      associated with GU risk (OR = 4.54, 95% CI = 0.95-21.83, P = .059). There was no
      publication bias identified in these comparisons. CONCLUSIONS: In Asia, 1 EPIYA-D
      motif was significantly associated with increased GC risk. Multiple EPIYA-C
      motifs were associated with increased PUD and DU risk, particularly in Asia. In
      the United States and Europe, multiple EPIYA-C motifs were associated with
      increased GC risk. Therefore, detection of polymorphic CagA EPIYA motifs may
      improve clinical prediction of disease risk.

PMID- 28445261
TI  - Behavior characteristics of the attention network of military personnel with high
      and low trait anxiety.
AB  - Converging evidence reveals significant increase in both state anxiety and trait
      anxiety during the past 2 decades among military servicemen and servicewomen in
      China. In the present study, we employed the Chinese version of the State-trait
      Anxiety Inventory (STAI) to examine trait and state anxiety in Chinese military
      servicemen and servicewomen. We further evaluated orienting, alerting and
      execution inhibition using the attention network test.Healthy military servicemen
      and servicewomen were recruited for the present study. The STAI was used to
      measure both state and trait anxiety and the attention network test was done to
      determine reaction time and accuracy rate.Fifty-seven subjects were eligible for
      the study. Their mean STAI score was 3.2 +/- 2.8 (range, 1-17) and 29 (50.9%)
      subjects were categorized into the high trait anxiety group and 28 (49.1%)
      subjects into the low trait anxiety group. The reaction time of the high trait
      anxiety group to incongruent, congruent, and neutral target was significantly
      longer than that of the low trait anxiety group (P < .05). Moreover, the accurate
      rate of the high trait anxiety group for incongruent, congruent, and neutral
      target was significantly higher than that of the low trait anxiety group (P <
      .05). Repeated analysis of variance showed marked effect of trait anxiety, cue
      types, and target types on reaction time. There was significant interaction among
      trait anxiety, target types, and cue types. Trait anxiety and target types also
      had marked effect on the accurate rate. Multivariate analysis showed no marked
      effect of trait anxiety on the alerting, orienting, and execution inhibition
      subnetwork.The present study has demonstrated that military service personnel
      with high trait anxiety requires more time for cognitive processing of external
      information but exhibits enhanced reaction accuracy rate compared to those with
      low trait anxiety. Our findings indicate that interventional strategies to
      improve the psychological wellbeing of military service personnel should be
      implemented to improve combat mission performance.

PMID- 28445262
TI  - Dose-dependence of PTH-related peptide-1 on the osteogenic induction of MC3T3-E1
      cells in vitro.
AB  - Parathyroid hormone (PTH), an 84-amino acid peptide, is an endocrine hormone that
      is secreted by parathyroid glands. PTH performs important functions in calcium
      regulation and bone remodeling. The PTH (1-34) named teriparatide, a 34-amino
      acid peptide derived from the N-terminus of PTH, conserves most of the functions
      of PTH, specifically the osteogenic capability. However, teriparatide is only
      used by injection and exhibits short duration. In addition, this PTH could not
      thoroughly expose active sites. In this study, a novel PTH-related peptide
      (designated PTHrP-1) derived from the N-terminus of PTH was added into the
      complete medium at different concentrations of PTHrP-1 (0, 50, 100, and 200
      ng/mL) to induce the MC3T3-E1 cells. PTHrP-1 was detected by high-performance
      liquid chromatography and matrix-assisted laser desorption/ionization-time-of
      flight mass spectroscopy. Cell morphology, cell proliferation, alkaline
      phosphatase (ALP), and ALP activity, osteocalcin concentration, and collagen type
      I (Col-I), osteopontin (OPN), and osteocalcin (OCN) mRNA expression by RT-PCR and
      protein expression by western blotting were observed and detected. The purity of
      the PTHrP-1 was 95.14%, and the PTHrP-1 can induce MC3T3-E1 cells into
      osteoblasts, thus improving ALP activity and OCN concentration, and increasing
      Col-I, OPN, and OCN mRNA expression and protein expression in MC3T3-E1 cell
      cultures. The PTHrP-1 proved to be an ideal active peptide. In addition, the
      osteogenic ability of PTHrP-1 at 200 and 100 ng/mL concentrations was not
      significantly different but significantly higher than 50 and 0 ng/mL groups.
      Results indicate that PTHrP-1 is a kind of active peptides that exhibits good
      biocompatibility with MC3T3-E1 cells and could improve cell proliferation and
      osteogenic differentiation. Moreover, PTHrP-1, at the preferable concentration of
      100 ng/mL, could effectively promote MC3T3-E1 cells into osteoblasts.

PMID- 28445263
TI  - Acupuncture for enhancing early recovery of bowel function in cancer: Protocol
      for a systematic review.
AB  - BACKGROUND: Cancer patients undergoing surgical procedure often suffer from bowel
      dysfunction and postoperative ileus (POI). Cancer management for early recovery
      of bowel function is still a challenging topic. Acupuncture has been commonly
      used in a variety of gastrointestinal diseases. The aim of this study is to
      evaluate the effects of acupuncture therapy to reduce the duration of POI and
      enhance bowel function in cancer patients. METHODS: We will systematically screen
      all randomized controlled trials (RCTs) published through electronically and hand
      searching. The following search engines including Medline, EMBASE, Cochrane
      CENTRAL, the Cumulative Index to Nursing and Allied Health Literature, Allied and
      Complementary Medicine Database, the Chinese Biomedical Literature Database, the
      China National Knowledge Infrastructure, VIP Information, Wanfang Data, one
      Japanese database (Japan Science and Technology Information Aggregator,
      Electronic) and 2 Korean Medical Databases (Korean Studies Information, and Data
      Base Periodical Information Academic) will be retrieved. Supplementary sources
      will be searched including gray literature, conference proceedings, and potential
      identified publications. Two reviewers will independently conduct the trial
      inclusion, data extraction and assess the quality of studies. The time to first
      passing flatus and time to first bowel motion will be assessed as the primary
      outcomes. Adverse effects, time to first bowel sound, visual analog scale (VAS)
      pain score, hospital stay, and postoperative analgesic requirement will be
      measured as secondary outcomes. Methodological quality will be evaluated
      according to the Cochrane risk of bias. Details of interventions will be assessed
      by the Standards for Reporting Interventions in Controlled Trials of Acupuncture
      (STRICTA) checklist. All analyses will be applied by RevMan (version 5.3) and
      StataSE (version 12). ETHICS AND DISSEMINATION: This systematic review will
      provide up-to-date information on acupuncture therapy for early recovery of bowel
      function in cancer patients. This review does not require ethical approval and
      will be reported in a peer-reviewed journal and presented at a relevant
      conference. TRIAL REGISTRATION NUMBER: PROSPERO CRD42016049633.

PMID- 28445264
TI  - Incremental cost of nosocomial bacteremia according to the focus of infection and
      antibiotic sensitivity of the causative microorganism in a university hospital.
AB  - To estimate the incremental cost of nosocomial bacteremia according to the
      causative focus and classified by the antibiotic sensitivity of the
      microorganism.Patients admitted to Hospital del Mar in Barcelona from 2005 to
      2012 were included. We analyzed the total hospital costs of patients with
      nosocomial bacteremia caused by microorganisms with a high prevalence and, often,
      with multidrug-resistance. A control group was defined by selecting patients
      without bacteremia in the same diagnosis-related group.Our hospital has a cost
      accounting system (full-costing) that uses activity-based criteria to estimate
      per-patient costs. A logistic regression was fitted to estimate the probability
      of developing bacteremia (propensity score) and was used for propensity-score
      matching adjustment. This propensity score was included in an econometric model
      to adjust the incremental cost of patients with bacteremia with differentiation
      of the causative focus and antibiotic sensitivity.The mean incremental cost was
      estimated at &OV0556;15,526. The lowest incremental cost corresponded to
      bacteremia caused by multidrug-sensitive urinary infection (&OV0556;6786) and the
      highest to primary or unknown sources of bacteremia caused by multidrug-resistant
      microorganisms (&OV0556;29,186).This is one of the first analyses to include all
      episodes of bacteremia produced during hospital stays in a single study. The
      study included accurate information about the focus and antibiotic sensitivity of
      the causative organism and actual hospital costs. It provides information that
      could be useful to improve, establish, and prioritize prevention strategies for
      nosocomial infections.

PMID- 28445265
TI  - Comparison of clinical outcomes after drug-eluting stent implantation in diabetic
      versus nondiabetic patients in China: A retrospective study.
AB  - Diabetes mellitus (DM) has been proved to be a predictor of adverse outcomes
      after percutaneous coronary intervention (PCI). Drug-eluting stents (DESs) could
      reduce the adverse events in DM patients. In this study, we aimed to analyze the
      clinical outcome after DES implantation in diabetic versus nondiabetic patients
      in China. Totally, 200 Chinese DM patients and 400 Chinese non-DM patients were
      enrolled in this retrospective study. Compared with non-DM patients, DM patients
      were more likely to have a higher incidence of cardiac death (3.5% vs. 1.0%, P =
      .048), stent thrombosis (2.5% vs. 0.5%, P = .044), target lesion
      revascularization (6.0% vs. 1.8%, P = .005), target vessel failure (15.5% vs.
      8.0%, P < .001), target lesion failure (14.0% vs. 4.3%, P < .001), myocardial
      infarction (4.5% vs. 1.5%, P = .030), and major adverse cardiac events (12.5% vs.
      5.0%, P = .001) at 2-year follow-up. However, the incidence of target vessel
      revascularization (7.5% vs. 5.5%, P = .340) was similar between DB and non-DB
      patients. Patients with DB (hazard ratio [HR] = 2.54, P = .001), older than 80
      years (HR = 1.33, P = .027) with hypercholesterolemia (HR = 1.03, P < .001),
      serum creatinine >177 MUmol/L (HR = 3.04, P = .011), a history of cerebral
      vascular accident (HR = 4.29, P = .010), or a history of myocardial infarction
      (HR = 31.4, P < .001) were more likely to experience adverse events. In China, DM
      could also be served as an independent predictor of adverse outcomes after DES
      implantation. These patients should be reexamined more frequently.

PMID- 28445266
TI  - Recurrent laryngeal nerve injury after thyroid and parathyroid surgery: Incidence
      and postoperative evolution assessment.
AB  - Recurrent laryngeal nerve (RLN) injury is a feared complication after thyroid and
      parathyroid surgery. It induces important postoperative morbidity. The present
      study aimed to assess the incidence of transient/permanent postoperative RLN
      injuries after thyroid and parathyroid surgery in the present cohort, to observe
      the timing of recovery, and to identify risk factors for permanent RLN injury
      after thyroidectomy.All consecutive patients operated on at our institution for
      thyroid and parathyroid pathologies from 2005 to 2013 were reviewed for vocal
      cord paresis. Vocal cord paresis was defined based on postoperative fiberoptic
      laryngoscopy. Demographics, intraoperative details, and postoperative outcomes
      were collected. Treatment types were assessed, and recovery times collected.
      Patients with vocal cord paresis on preoperative fiberoptic laryngoscopy were
      excluded from the analysis.The cohort included 451 thyroidectomies (756 nerves at
      risk) and 197 parathyroidectomies (276 nerves at risk). There were 63
      postoperative vocal cord pareses after thyroidectomy and 13 after
      parathyroidectomy. Sixty-nine were transient (10.6%) and 7 permanent (1.1%). The
      main performed treatment was speech therapy in 51% (39/76) of the patients.
      Median recovery time after transient injuries was 8 weeks. In the group with
      vocal cord paresis, risk factors for permanent injuries after thyroidectomy were
      previous thyroidectomy and intraoperative RLN injury on univariate analysis. On
      multivariate analysis, only intraoperative RLN injury remained significant.Most
      of the patients with transient postoperative RLN injury recovered normal vocal
      cord mobility within 6 months. The most common performed treatment was in this
      cohort speech therapy. Permanent RLN injuries remained rare (1.1%).

PMID- 28445267
TI  - Different clinical presentations of choledochal cyst among infants and older
      children: A 10-year retrospective study.
AB  - Choledochal cyst is a rare and often benign congenital cystic dilation throughout
      the biliary tree. Due to the benign nature of choledochal cyst among early
      diagnosed patients, the clinical assumption and diagnosis seem to be of utmost
      significance. Therefore, we sought to assess different clinical manifestations of
      choledochal cyst and relevant laboratory findings in infants and older
      children.Retrospectively, medical records of all patients with the diagnosis of
      choledochal cyst between 2005 and 2015 were reviewed. Demographic data, initial
      clinical presentation, positive findings on physical examination, history of any
      remarkable behavior such as persistent and unexplained crying and poor feeding,
      and diagnostic imaging modalities were listed. In addition, laboratory values for
      total and direct bilirubin, alkaline phosphatase, alanine transaminase, aspartate
      transaminase, prothrombin time, and partial thromboplastin time (PTT) were
      recorded for each patient. Patients were divided into 2 groups; younger than 1
      year-old (infants), and 1 year to 18 years old (older children). Demographic
      data, clinical data, and laboratory values were compared between the infants and
      older children.Thirty-two patients with a diagnosis of choledochal cyst were
      included in the study: 9 patients (28.12%) were infants and 23 patients (71.87%)
      were older children. Abdominal pain was the most common presenting symptom
      (62.5%), followed by nausea/vomiting (59.4%) and jaundice (28.1%). None of the
      patients presented with the classic triad of abdominal pain, jaundice, and right
      upper quadrant mass. Seventeen older children (73.91%) presented with nausea and
      vomiting, while 2 subjects (22.22%) in the infantile group presented with this
      feature (P = .01). Similarly, abdominal pain was found in 20 older children
      (86.95%); however, none of the infants presented with abdominal pain at diagnosis
      (P < .001). By contrast, the abdominal mass was more detected in infants than the
      older children (33.33% vs. 0%, P = .01). In terms of laboratory values, the
      median PTT was 44 and 36 s in infants and older children, respectively (P =
      .04).Infants were more likely to present with abdominal mass and older children
      were more likely to have nausea, vomiting, and abdominal pain. Furthermore,
      infants had more prolonged PTT than older children, implying a potential bleeding
      tendency.

PMID- 28445268
TI  - The use of mifepristone in abortion associated with an increased risk of uterine
      leiomyomas.
AB  - To investigate the association between widespread use of mifepristone in
      abortions and risk of uterine leiomyomas.We conducted a case-control study of 305
      patients with uterine leiomyomas between January 2011 and July 2012; 311 women
      with ordinary vaginitis were selected as controls during the same period. Data
      were collected by questionnaires (including past history, life history,
      menstruation history, reproductive history, abortion history, the use of
      mifepristone, and uterine leiomyomas risk factors) and calculated by univariate
      and multivariate conditional logistic regression analyses; odds ratios and its
      95% confidence interval were calculated to estimate the risk for uterine
      leiomyomas.Abortion with mifepristone was one of the risk factors for uterine
      leiomyomas, and the risk increased with increasing frequency of mifepristone use.
      Family history of uterine leiomyomas, body mass index, age at menarche, number of
      full-term delivery, and medical abortion history were also correlated with
      uterine leiomyomas.The use of mifepristone in abortion will increase the risk to
      develop uterine leiomyomas.

PMID- 28445269
TI  - Weekend versus weekday admission and short-term mortality: A meta-analysis of 88
      cohort studies including 56,934,649 participants.
AB  - It is widely accepted that higher mortality related to weekend admissions
      basically exists; however, there has been no systematic exploration of whether
      weekend admissions are associated with higher risk of death in patients on the
      basis of certain diagnoses, geographic regions, and study subtypes.A meta
      analysis was performed according to the reporting guidelines of the Meta-analysis
      of Observational Studies in Epidemiology (MOOSE Compliant). Literature search was
      conducted using electronic databases. Primary outcome was short-term (<=30-day)
      mortality. Patients were divided into 7 regions (North America, South America,
      Europe, Asia, Oceania, Africa, and Antarctica) for subgroup analyses and into 7
      categories evaluating 24 major diagnoses. Pooled odds ratio (OR) with 95%
      confidence interval (CI) was calculated with DerSimonian and Laird random-effects
      models.Eighty-eight studies including 56,934,649 participants met our inclusion
      criteria. Overall pooled adjusted and crude OR of weekend to weekday admission
      for short-term mortality was 1.12 (95% CI, 1.07-1.18; I = 97%) and 1.16 (95% CI,
      1.14-1.19; I = 97%), respectively. In subgroup analyses, higher risk of death on
      the weekend was significantly identified in patients living in all five
      continents (North America, South America, Europe, Asia, and Oceania). However,
      significant weekend effect was identified only in 15 of 24 diagnostic groups.
      Patients admitted on the weekend were more likely to die in an emergency
      situation (crude OR = 1.17, 95% CI, 1.12-1.22).Although weekend admissions were
      associated with higher risk of death compared with weekday admissions on all five
      continents, the effect was limited to certain diagnostic groups and admission
      subtypes. Weekend effect remains highly heterogeneous and limited, suggesting
      that further well-conducted cohort studies might be informative.

PMID- 28445270
TI  - Pooled analysis on the necessity of random 4-quadrant cervical biopsies and
      endocervical curettage in women with positive screening but negative colposcopy.
AB  - Controversy remains over whether random cervical biopsies and endocervical
      curettage (ECC) should be used in women with positive screening but negative
      colposcopy. Our paper aims to determine the indications for random biopsies and
      ECC among these screened positive women.Three thousand two hundred thirteen women
      with any positive screening test result but negative colposcopy, who received
      random 4-quadrant biopsies, were pooled from 17 population-based cervical cancer
      screening studies done in China from 1999 to 2008. The detection rates of
      cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN grade 3 or
      worse (CIN3+) stratified by cytology and high-risk human papillomavirus (HR-HPV)
      status were assessed, as well as the false negative rates for CIN2+ and CIN3+ by
      random biopsies without ECC.Compared with women with negative cytology and
      positive HR-HPV, those with atypical squamous cells of undetermined
      significance/low-grade squamous intraepithelial lesion (ASC-US/LSIL) and negative
      HR-HPV had the equivalent lower risks of CIN2+ and CIN3+, but ascending risks
      were observed in the groups of ASC-US/LSIL and positive HR-HPV, and atypical
      glandular cells/atypical squamous cells cannot exclude high-grade squamous
      intraepithelial lesion/high-grade squamous intraepithelial lesion or worse
      (AGC/ASC-H/HSIL+). If random biopsies were only taken without ECC, 9.3% of CIN2+
      and 18.5% of CIN3+ would have been missed.For women with any positive screening
      but negative colposcopy, in areas with good cytological infrastructure, it was
      necessary to perform random biopsies plus ECC on those with cytological ASC
      US/LSIL and positive HR-HPV, AGC, ASC-H, or HSIL+. In contrast, those with other
      results should be followed up.

PMID- 28445271
TI  - Identifying pretreatment baseline factors predictive of distant metastasis in
      patients with nasopharyngeal carcinoma after radiotherapy.
AB  - This retrospective study was performed to identify pretreatment baseline factors
      that could predict the development of distant metastasis (DM) in patients with
      nasopharyngeal carcinoma (NPC).A cohort of 119 NPC patients undergoing
      radiotherapy (RT) or chemoradiotherapy (CRT) were recruited into the study. Among
      them, 51 developed DM (DM group) within 3 years after treatment and 68 did not
      (DM-free group). Various clinicopathological factors were measured before the
      treatment and analyzed by univariate as well as multivariate analyses for the
      potential correlation with DM development.Univariate analysis revealed that
      increased peripheral lactate dehydrogenase (LDH) level, lower lymphocyte-monocyte
      ratio (LMR), higher neutrophil-lymphocyte ratio (NLR), advanced American Joint
      Committee on Cancer (AJCC) stage, advanced T stage, and advanced N stage were
      significantly correlated with the presence of DM. Multivariate analysis
      identified advanced AJCC stage and high LDH level were independent predictive
      factors for DM.Routinely measured pretreatment clinical factors, including AJCC
      state and serum LDH level, could independently predict DM. These factors will
      benefit the selection of appropriate treatment options and improve the overall
      survival of NPC patients.

PMID- 28445272
TI  - Elevated serum plasma fibrinogen is associated with advanced tumor stage and poor
      survival in hepatocellular carcinoma patients.
AB  - Hyperfibrinogenemia has been reported to be a predictor of poor prognosis in
      cancer patients, and in hepatocellular carcinoma (HCC) patients, survival remains
      uncertain and unpredictable. The aim of the present study was to evaluate the
      association between the level of plasma fibrinogen and overall survival in HCC
      patients.Overall, 308 patients with histologically proven HCC were included in
      our study. Univariate and multivariate analyses were performed to identify
      predictive risk factors for the rates of overall survival and tumor
      recurrence.Patients in the high-fibrinogen-level group were more likely to have
      advanced stage HCC, portal vein invasion, and tumors that were greater in number
      and larger in diameter than were patients in the low-fibrinogen-level group (all
      P < .05). The long-term overall survival rate of patients in the high-fibrinogen
      group was much lower than that of patients in the normal-fibrinogen group (P =
      .008), and similar outcomes were observed in the subgroup of patients who
      underwent radical therapies for HCC (P = .003). The results of the univariate and
      multivariate analyses indicated that high plasma fibrinogen remained
      independently associated with poorer overall survival. In addition, high plasma
      fibrinogen levels were associated with nonresponse to transarterial
      chemoembolization (TACE) (P < .001).Elevated plasma fibrinogen was independently
      associated with advanced HCC stage, poor prognosis, and nonresponse to TACE and
      may, therefore, serve as a valuable clinical biomarker for predicting prognosis
      in HCC patients.

PMID- 28445273
TI  - Staged management of open Lisfranc injury: Experience from 14 patients.
AB  - There are still controversies on the management and outcome of open Lisfranc
      injury in available studies. This study evaluates the staged management of
      Lisfranc injury and its complications.Patients who received a staged strategy for
      open Lisfranc injury were reviewed.One patient with degloving injury suffered
      from partial skin and hallux necrosis which was treated by debridement, hallux
      amputation, definitive internal fixation, and local flap transfer on the 12th day
      after first stage management. A definitive internal fixation and simultaneous
      skin graft or flap coverage were performed in another 3 patients with soft tissue
      defects. Other patients without soft tissue problems underwent a second stage of
      definitive internal fixation. Bone union was observed on the 12.5th week after
      definitive surgery. The median AOFAS midfoot score at the last follow-up was 74.4
      +/- 8.7, while the average VAS score was 2.2 +/- 1.8. The average return-to-work
      time was 8th months postoperatively in 9 patients. Flap necrosis, infection,
      implant failure, nonunion, and osteomyelitis were not observed during the follow
      up. Two patients received Lisfranc arthrodesis for persistent pain due to
      posttraumatic arthritis.In the management of open Lisfranc injury, surgeons must
      consider soft tissue condition. Staged strategy is a rational protocol for this
      severe injury. Temporary K-wire fixation after early radical debridement and
      realignment will facilitate the definitive internal fixation until soft tissue
      condition improves, which also can decrease the soft tissue complication.

PMID- 28445274
TI  - Clinical analysis of cervical intraepithelial neoplasia with vaginal
      intraepithelial neoplasia.
AB  - The purpose of this prospective cohort study is to evaluate the importance of
      screening and its diagnostic accuracy compared with the pathological diagnosis of
      cervical intraepithelial neoplasia (CIN) with vaginal intraepithelial neoplasia
      (VAIN).The prospective study enrolled 419 patients (pts) and was conducted
      between February 1, 2015 and January 31, 2016 at Beijing Obstetrics and
      Gynecology Hospital, Capital Medical University.All enrolled pts underwent
      multipoint biopsy of cervix and vaginal wall directed by colposcopy. All samples
      of biopsy underwent pathological examination. Among them, 201 pts (48.0%) were
      diagnosed with CIN, 218 pts (52.0%) were diagnosed with cervicitis, and 51 pts
      (12.2%) were diagnosed with VAIN. It was found that the incidence of CIN in pts
      was 4 times higher than that of VAIN. In all 419 patients enrolled, 218 pts had
      cervicitis with 13 pts (6.0%) of VAIN. There were 201 pts of CIN with 38 pts
      (18.9%) of VAIN: including 53 pts of CIN3 with 12 pts (22.6%) of VAIN; 49 pts of
      CIN2 with 9 pts of VAIN (18.4%), and 99 pts of CIN1 with 17 pts of VAIN (17.2%).
      The incidence of CIN with VAIN (18.9%) was significantly higher than cervicitis
      with VAIN (6.0%) (chi = 16.39, P = .00). Our results showed that there was a
      significant consistency between cervical lesions and vaginal lesions (chi =
      135.91, P = .00), which indicated that the increase of CIN grades may be related
      to an increase of the VAIN grades. Our results also showed the significant (p <
      .05) increase of CIN and VAIN with age (<40 years Kappa = 0.04; 40-50 years Kappa
      = 0.11; >50 years Kappa = 0.28).This study showed that cytological test can be
      used as a routine screening method for cervical lesions and vaginal diseases. If
      the cytology result shows abnormality, and pathological examination confirms that
      there is no obvious abnormal cervical disease, colposcopy directed vaginal
      multipoint biopsy should be conducted to exclude vaginal disease. All patients of
      CIN should routinely undergo vaginal multipoint biopsy (1/3 upper vagina),
      especially in patients with high-grade CIN and age older than 50 years.

PMID- 28445275
TI  - Cases of primary malignant melanoma and melanocytosis of the esophagus observed
      by magnifying endoscopy: Application to differential diagnosis: case series.
AB  - RATIONALE: Primary malignant melanoma of the esophagus (PMME) is a rare disease
      with an extremely poor prognosis. In contrast, melanocytosis is a benign
      condition defined as melanocytic proliferation with melanin deposition. PMME is
      often accompanied by melanocytosis, but differentiating between them is difficult
      because of their similar appearance. PATIENT CONCERNS: Here, we reported 3 PMME
      cases, 2 with melanocytosis. DIAGNOSES: Magnifying endoscopy revealed
      characteristic non-uniform pigmented spots along deformed intrapapillary
      capillary loops (IPCLs) in PMME, while melanocytosis showed fine granule-like or
      linearly arranged spots and intact IPCLs. INTERVENTIONS: The patients underwent
      endoscopic or surgical resection of each lesion. OUTCOMES: Histologically,
      magnified images reflected melanocyte growth. For cases 1 and 2, the patients
      remained disease-free for 61 and 15 months after endoscopic resection,
      respectively. In case 3, liver metastases developed two months after surgery, and
      the patient died from liver failure after six months. LESSONS: This is the first
      report describing differences in magnified views of the 2 diseases, which aids a
      differential diagnosis.

PMID- 28445276
TI  - Correlation between prefrontal-striatal pathway impairment and cognitive
      impairment in patients with leukoaraiosis.
AB  - Our study aimed to investigate the changes of white matter microstructure of
      cortico-subcortical pathways using diffusion tensor imaging (DTI), and to explore
      the relationship between abnormal parameters of DTI and cognitive function
      underlying in patients with leukoaraiosis (LA).A total of 42 patients with LA and
      42 age- and sex-matched healthy controls were recruited from Beijing Chaoyang
      Hospital, Capital Medical University between January 2012 and December 2012. All
      the subjects underwent scans of conventional magnetic resonance imaging and DTI,
      and a comprehensive neuropsychological battery was utilized. The regions of
      interest (ROIs) were located at the white matter of centrum semiovale, anterior
      and posterior periventricular white matter, basal ganglia, corpus callosum. The
      averaged values of mean diffusivity (MD) and fractional anisotropy (FA) were
      quantified both within white matter lesions (WMLs) and normal appearing white
      matter (NAWM). A linear regression analysis was performed to assess the
      association between diffusion parameters and decline in cognitive
      domains.Patients with LA were associated with comprehensive cognitive function
      deficits. We found that significantly decreased FA and increased MD in WMLs at
      the 5 ROIs than that of NAWM and controls (P < .05). The values of FA in NAWM
      were significantly lower and MD in NAWM were significantly higher at centrum
      semiovale and posterior periventricular white matter than that of controls (P <
      .05). The values of FA in WMLs at anterior periventricular white matter were
      positively related to the performances of cognition in patients with LA (P <
      .05). The values of FA in NAWM located at anterior periventricular white matter
      were positively related to the score of Digit-symbol test (r = 0.446, P = .002).
      The values of FA in NAWM located at anterior periventricular white matter
      correlated inversely with the Z scores of executive function (r = -0.418, P =
      .03).In our study, patients with LA exhibited significant cognitive impairment
      especially in the domains of executive function. The technique of DTI revealed
      that the reduced FA and increased MD at the corresponding regions of cortico
      subcortical pathways in patients with LA. DTI may be of great help for an early
      pathology of white matter microstructure underlying in patients with LA.

PMID- 28445277
TI  - Cancer studies based on secondary data analysis of the Taiwan's National Health
      Insurance Research Database: A computational text analysis and visualization
      study.
AB  - There has been a surge in the academic publication output based on secondary
      analyses of the data from the Taiwan's National Health Insurance claim records.
      It has become a challenge to comprehend such a rapid expansion of the literature.
      Therefore, this study aimed to explore the conceptual content of National Health
      Insurance Research Database-based cancer research, using the abstract of articles
      extracted from PubMed between 2002 and 2015. Search terms including "National
      Health Insurance Research Database (NHIRD) AND Taiwan," "Taiwan AND population
      based," and "Taiwan AND nationwide" were used to search in PubMed with the
      publication date limited to between 1997 and 2015. The retrieved articles were
      manually screened to retain only those that were cancer-related and were based on
      secondary data analysis of the NHIRD. A total 589 articles were selected for
      subsequent text mining using the R software. Among the 589 articles, the top 5
      most studied cancer types were breast (16.3%), lung (11.4%), colorectal (10.4%),
      liver (8.3%), and prostate (7.5%). The articles that received the highest number
      of citations by PubMed Central articles were cited 92 times. The top 3 most
      frequently occurred keywords in the abstracts of the 589 articles were cancer,
      patient, and risk, with 3670, 2535, and 1652 times, respectively. Analysis of key
      conception indicated that the most common conceptions were diabetes, survival,
      breast cancer, lung cancer, and colorectal cancer. In conclusion, in this study
      of 589 published articles on secondary data analysis of the NHIRD, indexed by
      PubMed between 2002 and 2015, we found that while the risk factors of cancer,
      treatment of cancer, and survival of cancer patients were popular research
      topics, end-of-life cancer care issues were less studied. Further studies should
      explore these areas since they are as important as treatment of the disease
      itself for many patients.

PMID- 28445278
TI  - Analysis of treatment of large abdominal malignancies in children complicated
      with abdominal compartment syndrome: Report of six cases.
AB  - To explore effective treatment of large abdominal malignancies in children
      complicated with abdominal compartment syndrome (ACS).Six children with large
      abdominal malignancies complicated with ACS were admitted to our department from
      January 2013 to January 2016, and the changes in their breathing, heart rate,
      oxygen saturation, abdominal circumference, bladder pressure, and urine output,
      as well as the treatment measures and outcomes, were retrospectively analyzed.The
      6 children included 1 child with bilateral nephroblastoma, 1 child with abdominal
      alveolar rhabdomyosarcoma, 1 child with right ovarian malignant teratoma
      complicated with abdominal glioma, 1 child with abdominal malignant teratoma, 1
      child with right nephroblastoma, and 1 child with left adrenal gland
      neuroblastoma. All patients were treated in a timely manner. The first 4 children
      underwent abdominal cavity decompression through surgical resection of the tumor,
      and the ACS was successfully cured allowing for follow-up care, whereas the last
      2 patients failed to receive emergency surgery and eventually died due to the
      gradual aggravation of ACS.Decompression through surgical resection of the tumor
      is the only effective measure for treating large abdominal malignancies in
      children complicated with ACS.

PMID- 28445279
TI  - Promoter hypermethylation of MGMT gene may contribute to the pathogenesis of
      gastric cancer: A PRISMA-compliant meta-analysis.
AB  - BECKGROUND: The association of MGMT (O-methyguanine deoxyribonucleic acid
      methyltransferase) promoter hypermethylation with gastric cancer (GC) risk has
      been studied extensively, but the results remained unclear. Here, we performed a
      meta-analysis to evaluate whether promoter hypermethylation of the MGMT gene
      contributed to gastric pathogenesis. METHODS: Relevant studies were identified by
      retrieving the PubMed, Web of Science, Embase, and China National Knowledge
      Infrastructure (CNKI) databases. The Newcastle-Ottawa Scale was applied to assess
      methodological quality of the included studies. Pooled odds ratios (ORs) and 95%
      confidence intervals (95% CIs) were calculated to evaluate the association of
      MGMT promoter hypermethylation with gastric pathogenesis. Moreover, STATA 12.0
      software was used to summarize the extracted data in this meta-analysis. RESULTS:
      Seventeen studies, comprising 1736 cases and 1291 controls, were included in this
      meta-analysis. The frequency of MGMT promoter hypermethylation in the GC group
      (32.97%) was significantly higher than those in the control group (18.00%) (OR =
      2.83, CI = 1.93-4.15, P < .05). When stratified by cancer subtype, the results
      indicated that the frequency of MGMT promoter hypermethylation was significantly
      higher in gastric adenocarcinoma than in control group (OR = 3.47, CI = 1.06
      11.35, P < .05). In addition, MGMT promoter hypermethylation significantly
      promoted distant metastasis and lymph node (LN) metastasis of gastric tumor (for
      distant metastasis, OR = 4.22, CI = 2.42-7.37, P < .05; for LN metastasis, OR =
      1.56, CI = 1.14-2.13, P < .05). A significant association between MGMT promoter
      hypermethylation and TNM-stage was also found in the present meta-analysis (OR =
      2.70, CI = 1.79-4.08, P < .05). CONCLUSION: The results of this meta-analysis
      suggested that MGMT gene-promoter hypermethylation was significantly associated
      with an increased risk of GC, especially in Asians. Furthermore, MGMT gene
      promoter hypermethylation might be correlated with the distant metastasis and LN
      metastasis of GC.

PMID- 28445280
TI  - Clinical outcome after endoscopic submucosal dissection for early gastric cancer
      of absolute and expanded indication.
AB  - This study evaluated the clinical outcome of endoscopic submucosal dissection
      (ESD) in minute submucosa (SM) invasion or undifferentiated early gastric cancer
      (EGC) and analyzed factors related to local recurrence after ESD.We
      retrospectively reviewed the chart of EGC patients, who underwent ESD at our
      tertiary hospital between January 2009 and 2015. The patients' characteristics
      and clinical outcomes were compared among an absolute indication, minute SM
      invasion, and undifferentiated EGC group.Of 885 total patients, 729 composed the
      absolute indication group; 65, the differentiated, SM invasion group; and 51, the
      undifferentiated, confined mucosa group. Follow-up was conducted for average (+/-
      standard deviation) 34.12 (+/- 10.6) months; as compared to the absolute
      indication group, both en bloc resection and curative resection rate were low in
      the other 2 groups, but there were no significant differences in procedure
      related complication, local recurrence, and survival rate. Comparing the cases of
      ESD performed at our hospital from 2005 to 2009 with those performed between 2009
      and 2015, en bloc resection (80.5% vs 89.1%, P = .001) and curative resection
      rate (86.2% vs 92.1%, P = .011) were higher in the latter study. Noncurative
      resection and tumor size of more than 2 cm were factors associated with local
      recurrence.ESD in minute SM invasion or undifferentiated EGC showed an
      unfavorable short-term outcome as compared to that in the absolute indication
      group, but there were no differences in local recurrence and overall survival
      rate. Therefore, in minute SM invasion or undifferentiated EGC patients, ESD
      could be recommended as a therapeutic option.

PMID- 28445281
TI  - Relationship between the abnormal diastolic vortex structure and impaired left
      ventricle filling in patients with hyperthyroidism.
AB  - Intraventricular hydrodynamics plays an important role in evaluating cardiac
      function. Relationship between diastolic vortex and left ventricular (LV) filling
      is still rarely elucidated. The aim of this study was to evaluate the evolution
      of vortex during diastole in hyperthyroidism (HT) and explore the alteration of
      hydromechanics characteristics with sensitive indexes.Forty-three patients
      diagnosed with HT were classified into 2 groups according to whether myocardial
      damage existed: simple hyperthyroid group (HT1, n = 21) and thyrotoxic
      cardiomyopathy (HT2, n = 22). Twenty-seven age- and gender-matched healthy
      volunteers were enrolled as the control group. Offline vector flow mapping (VFM
      model) was used to analyze the LV diastolic blood flow patterns and fluid
      dynamics. Hemodynamic parameters, vortex area (A), circulation (C), and
      intraventricular pressure gradient (DeltaP), in different diastolic phases
      (early, mid, and late) were calculated and analyzed.HT2, with a lower E/A ratio
      and left ventricular ejection fraction (LVEF), had a larger left atrium diameter
      (LAD) compared with those of the control group and HT1 (P < .05). Compared with
      the control group, the vortex size and strength, intraventricular pressure
      gradient during early and mid-diastole were higher in HT1 and lower in HT2 (P <
      .05). And in late diastole, the vortex size and strength, intraventricular
      pressure gradient of HT2 became higher than those of the control group (P < .05).
      Good correlation could be found between CE and E/A (P < .05), CM and DeltaPM (P <
      .01), CL and FT3 (P < .05).VFM is proven practical for detecting the relationship
      between the changes of left ventricular diastolic vortex and the abnormal left
      ventricular filling.

PMID- 28445282
TI  - A case report of Sjogren syndrome manifesting bilateral basal ganglia lesions.
AB  - RATIONALE: Peripheral neurological complications in primary Sjogren's syndrome
      (pSS) seem the most common, however the involvement of central nervous system
      (CNS) remains unclear. While abnormalities in pSS revealed by brain magnetic
      resonance imaging (MRI) are usually small discrete hyperintense areas in the
      white matter on T2-FLAIR weighted MRI, massive brain lesions have been rarely
      reported, particularly in bilateral basal ganglia. PATIENT CONCERNS: A 51-year
      old woman exhibited dizziness, slurred speech and hemiplegia as a manifestation
      of pSS. Brain MRI revealed bilateral and symmetrical lesions extending into the
      basal ganglia, corona radiata and corpus callosum. DIAGNOSES: Primary Sjogren's
      syndrome was diagnosed on the basis of clinical features, abnormal Schirmer's
      test and tear break-up time (BUT) findings, high levels of anti-Sjogren's
      syndrome-related antigen A (anti-SSA) (Ro) and anti-Sjogren's-syndrome-related
      antigen B (anti-SSB) (La) antibodies, and positive labial minor salivary gland
      biopsy results. INTERVENTIONS: She was treated with intravenous
      methylprednisolone and discharged on oral steroid therapy of prednisolone
      acetate. OUTCOMES: The patient had an excellent response to steroid therapy.
      LESSONS: The present case suggests that symmetry bilateral lesions can occur as a
      symptom of pSS, which could be induced by an autoimmune mechanism.

PMID- 28445284
TI  - Appendiceal foreign body in an infant.
AB  - RATIONALE FOR THIS CASE REPORT: Many children are hospitalized because of foreign
      body ingestion. In such circumstances, the gastroenterologist must consider the
      timing of ingestion; the size, type, and location of the object ingested; and the
      patient's symptoms. But appendiceal foreign body in infant is very rare. PATIENT
      CONCERNS: A 12-month-old boy visited because of swallowing small objects 2 weeks
      ago. Three small beads were found in the right lower quadrant on abdominal
      radiography. A 7-year-old boy was admitted for treatment of appendiceal foreign
      body, which was detected by accident 3 months ago. DIAGNOSES, INTERVENTIONS, AND
      OUTCOMES: A 7-year-old boy had abdominal pain and underwent immediate
      appendectomy. However, the 12-month-old child was asymptomatic, which led to
      deliberation in regard to wait time for an appendectomy in younger children with
      asymptomatic appendiceal foreign body. He underwent prophylactic appendectomy
      after 2 months. MAIN LESSONS: An appendiceal foreign body is very rare in infant
      and there are currently no treatment guidelines. We report 2 cases of appendiceal
      foreign body including infant who gave us difficult decisions.

PMID- 28445283
TI  - Association between plasma homocysteine concentration and the risk of all-cause
      death in adults with diastolic dysfunction in a community: A 13-year cohort
      study.
AB  - Hyperhomocysteinemia (HHCYS) has been associated with systolic heart failure.
      However, it is still unknown that serum homocycsteine level was useful in
      predicting the outcome in patients with diastolic dysfunction. We conducted a
      cohort study to determine if HHCYS was associated with poor prognosis in
      diastolic dysfunction patients. The Chin-Shan Community Cardiovascular Cohort
      (CCCC) study was designated to investigate the trends of cardiovascular morbidity
      and mortality in a community. Individuals who were 35 years and above were
      enrolled. Participants were categorized by homocysteine concentration quartiles.
      We used multivariate Cox proportional hazards models to calculate the hazard
      ratio (HR) of the 4th quartiles versus the 1st quartile. Area under the receiver
      operating characteristic (ROC) curve was to compare prediction measures. A total
      of 2020 participants had completed the echocardiography examination, and 231
      individuals were diagnosed as diastolic dysfunction. A total 75 participants had
      died during follow-up period. HHCYS was found to be significantly associated with
      poor prognosis. The adjusted HR for homocysteine level was 1.07 (95% confidence
      interval [CI], 1.01-1.14). Participants in the highest quartile had a 1.90 (95%
      CI, 0.88-4.12, P for trend, .026) fold risk for all cause death, compared with
      those in the lowest quartiles. The HR was 1.88 (95% CI, 1.07-3.29) using 11.11
      MUmol/L as cut point for hyperhomocysteine. HHCYS was significantly associated
      with poor prognosis in diastolic dysfunction participants in the community.

PMID- 28445285
TI  - Association between vitamin D receptor BsmI polymorphism and bone mineral density
      in pediatric patients: A meta-analysis and systematic review of observational
      studies.
AB  - BACKGROUND: Vitamin D and the vitamin D receptor (VDR) are important in the
      metabolic processes that affect bone mineral density (BMD). However, the effect
      of VDR BsmI polymorphism on BMD in pediatric patients is still unclear. METHODS:
      Eligible studies were identified from the following electronic databases: PubMed,
      Embase, the Cochrane Library, and the Chinese CNKI and Wanfang databases before
      October 1, 2016. Data were extracted from the eligible studies, and associations
      between VDR BsmI polymorphism and BMD in pediatric patients were estimated with
      weighted mean differences (WMDs) and 95% confidence intervals (CIs). Subgroup
      analysis of ethnicity and sensitivity analyses were used to identify sources of
      heterogeneity. RESULTS: A significant difference was observed between VDR BsmI
      polymorphism and pediatric BMD levels of the lumbar spine (LS) in the corecessive
      model (bb vs BB + Bb: WMD = -0.23, 95% CI [-0.35, -0.11], P < 0.01). No
      significant relationship was found in the dominant, recessive, or codominant
      models for LS BMD (BB vs Bb: WMD = -0.56, 95% CI [-1.58, 0.46], P = 0.29; BB vs
      bb: WMD = -0.54, 95% CI [-1.49, 0.41], P = 0.27; and BB vs Bb + bb: WMD = -0.45,
      95% CI [-1.71, 0.26], P = 0.22). In addition, we found no remarkable association
      between the BsmI polymorphism and BMD levels of the femoral neck (FN) in children
      (BB vs Bb: WMD = -1.08, 95% CI [-3.13, 0.96], P = 0.30; BB vs bb: WMD = 0.98, 95%
      CI [-0.89, 2.85], P = 0.31; BB vs Bb + bb: WMD = -0.061, 95% CI [-0.30, 0.17], P
      = 0.61; and bb vs BB + Bb: WMD = 0.82, 95% CI [-0.59, 2.32], P = 0.25).
      CONCLUSION: Our meta-analysis found that the VDR BsmI genetic polymorphism was
      correlated with LS BMD level in pediatric patients: compared with those with the
      B allele, children with the bb genotype were less likely to have lower BMD
      levels. No significant difference was identified in the pediatric FN BMD levels.

PMID- 28445286
TI  - Remote ischemic preconditioning improves the cognitive function of elderly
      patients following colon surgery: A randomized clinical trial.
AB  - BACKGROUND: Cognitive function impairment is one of the most common complications
      in elderly patients after surgery, and an ideal nonpharmacological therapy has
      not yet been identified. Thus, we hypothesized that remote ischemic
      preconditioning could improve cognitive functions in elderly patients after
      surgery and investigated the mechanism underlying this effect. METHODS: Ninety
      patients classified as American Society of Anaesthesiologists (ASA) physical
      status of 2 or 3 and aged 65 to 75 years who were scheduled for elective colon
      surgery under general anesthesia were randomly allocated to either a remote
      ischemic preconditioning group (Group R, n = 45) or a control group (Group C, n =
      45). Remote ischemic preconditioning was performed by applying a static pressure
      of 200 mm Hg with a blood pressure cuff wrapped around the right upper limb for 3
      ischemia cycles of 5 minutes each. RESULTS: The Montreal Cognitive Assessment
      (MoCA) scores between the 2 groups were not significantly different on the day
      before surgery or the seventh day after surgery, but the scores on the first day
      after surgery (26.87 +/- 0.84 vs 25.96 +/- 0.85, P < .001) and third day after
      surgery (27.49 +/- 0.66 vs 27.02 +/- 0.92, P = .009) were significantly higher
      for Group R than those for Group C. Moreover, remote ischemic preconditioning
      markedly decreased the serum concentrations of the interleukin-1beta (IL-1beta),
      tumor necrosis factor-alpha (TNF-alpha), and S100B proteins compared with the
      control group (P < .001). CONCLUSION: Remote ischemic preconditioning improves
      postoperative cognitive function in elderly patients following colon surgery. The
      cognitive protective effects of remote ischemic preconditioning are partially
      related to the inhibition of inflammation.

PMID- 28445287
TI  - Prognostic value of pretreatment 18F-FDG PET-CT for nasopharyngeal carcinoma
      patients.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a special subtype of head and neck
      cancer (HNC). At present, there are no highly specific prognostic markers to aid
      in tumor grading and guide patient treatment modalities for NPC. The prognostic
      value of pretreatment F-fluorodeoxyglucose positron emission tomography-computed
      tomography (F-PET-CT) in NPC patients is controversial and no consensus exists as
      to its predictive capability. METHODS: To analyze the predictive efficacy of F
      PET-CT imaging in NPC patients, data from MEDLINE, EMBASE, the Cochrane library,
      CBM, CNKI, and VIP (inception to July 2016) were accessed. Results from
      prospective and retrospective observational studies that used F-FDG PET to
      predict disease prognosis in NPC patients were used for analysis. Two authors
      independently assessed study quality and extracted data. Event-free survival
      (EFS) was considered the primary endpoint and overall survival rate (OS) was
      considered the secondary endpoint. RESULTS: Data from 14 studies and 1134
      patients were included in our analysis. The hazard ratios (HRs) of maximum
      standardized uptake value of primary tumor (SUVmax-T), metabolic tumor volume of
      primary tumor (MTV-T), and total lesional glycolysis of primary tumor (TLG-T) for
      EFS were 1.31 (95% confidence interval [CI], 1.11-1.55, P = .001), 2.38 (95% CI
      1.53-3.70, P < .001), and 1.65 (95% CI 0.76-3.59, P = .21), respectively. Among
      studies including TLG-T, those with a fixed SUV of 2.5 had an HR of 3.55 (95% CI,
      1.42-8.84, P = .007). The HRs of SUVmax-T and MTV-T for OS were 2.19 (95% CI,
      1.47-3.27, P < .001) and 2.69 (95% CI, 1.01-7.17, P = .05), respectively. Among
      studies including MTV-T, those with a fixed SUV of 2.5 had an HR of 4.07 (95% CI,
      2.22-7.46, P < .001). Tests used for assessing predictive value of pretreatment
      SUVmax, MTV, and TLG of lymph nodes for EFS and OS showed that these parameters
      did not have significant predictive value (P>.05). CONCLUSION: Our results
      suggested that SUVmax, MTV, and TLG (with a fixed SUV of 2.5) of primary tumors
      before treatment initiation may be independent prognostic factors for NPC
      patients; however, SUVmax, MTV, and TLG of metastatic lymph nodes are not.

PMID- 28445288
TI  - Association between proton pump inhibitors and hepatic encephalopathy: A meta
      analysis.
AB  - BACKGROUND & AIMS: Several studies have shown that proton pump inhibitors (PPIs)
      use can increase the risk of developing hepatic encephalopathy (HE) in patients
      with liver dysfunction. However, no definite conclusion is drawn because of study
      design limitations. Therefore, we conducted a meta-analysis to explore the
      association between PPIs and HE. METHODS: We searched PubMed, EMBASE, and the
      Cochrane Library from inception until November 2016. Data from the identified
      studies were combined using a random effects model, and odds ratios (ORs) were
      calculated. RESULTS: Three case-control studies were included. Compared with
      nonusers, hepatic insufficiency patients receiving PPIs therapy had a
      significantly increased risk of developing HE (OR = 1.76, 95% CI: 1.15-2.69),
      with notable heterogeneity (I = 61.4%, P = .075) and publication bias. No
      relevance was found between PPIs and HE after using the trim and fill method (OR
      = 1.360, 95%CI: 0.909-2.035, P = .135). CONCLUSIONS: PPIs are associated with a
      higher risk of HE among patients with chronic and acute liver dysfunction. A
      final conclusion cannot be drawn because of the limited number of studies and a
      lack of prospective studies.

PMID- 28445289
TI  - Vitamin K intake and the risk of fractures: A meta-analysis.
AB  - The association between dietary vitamin K intake and the risk of fractures is
      controversial. Therefore we perform a meta-analysis of cohort or nested case
      control studies to investigate the relationship between dietary vitamin K intake
      and the risk of fractures. A comprehensive search of PubMed and EMBASE (to July
      11, 2016) was performed to identify cohort or nested case-control studies
      providing quantitative estimates between dietary vitamin K intake and the risk of
      fractures. Summary relative risk (RRs) with corresponding 95% confidence
      intervals (CIs) were pooled by using a random-effects model. Four cohort studies
      and one nested case-control study, with a total of 1114 fractures cases and
      80,982 participants, were included in our meta-analysis. Vitamin K intake in all
      included studies refers exclusively to the intake of phylloquinone (vitamin K1),
      which is the predominant form of vitamin K in foods. We observed a statistically
      significant inverse association between dietary vitamin K intake and risk of
      fractures (highest vs. the lowest intake, RR = 0.78, 95% CI: 0.56-0.99; I =
      59.2%, P for heterogeneity = .04). Dose-response analysis indicated that the
      pooled RR of fracture for an increase of 50 MUg dietary vitamin K intake per day
      was 0.97 (95% CI: 0.95-0.99) without heterogeneity among studies (I = 25.9%, P
      for heterogeneity = .25). When stratified by follow-up duration, the RR of
      fracture for dietary vitamin K intake was 0.76 (95% CI: 0.58-0.93) in studies
      with more than 10 years of follow-up. Our study suggests that higher dietary
      vitamin K intake may moderately decrease the risk of fractures.

PMID- 28445290
TI  - Efficacy of quadriceps vastus medialis dry needling in a rehabilitation protocol
      after surgical reconstruction of complete anterior cruciate ligament rupture.
AB  - BACKGROUND: Several new rehabilitation modalities have been proposed after
      anterior cruciate ligament (ACL) reconstruction. Among these, trigger point dry
      needling (TrP-DN) might be useful in the treatment of myofascial pain syndrome
      associated with ACL reconstruction to reduce pain intensity, increase knee
      flexion range and modify the mechanical properties of the quadriceps muscle
      during late-stage rehabilitation. To date, this is the first randomized clinical
      trial to support the use of TrP-DN in the early rehabilitation process after ACL
      reconstruction. The aim of this study was to determine the pain intensity, range
      of motion (ROM), stability, and functionality improvements by adding quadriceps
      vastus medialis TrP-DN to the rehabilitation protocol (Rh) provided to subacute
      ACL reconstructed patients. METHODS: This randomized, single-blinded, clinical
      trial (NCT02699411) included 44 subacute patients with surgical reconstruction of
      complete ACL rupture. The patients were randomized into 2 intervention groups: Rh
      (n = 22) or Rh + TrP-DN (n = 22). Pain intensity, ROM, stability, and
      functionality were measured at baseline (A0) and immediately (A1), 24 hours (A2),
      1 week (A3), and 5 weeks (A4) after the first treatment. RESULTS: Comparing
      statistically significant differences (P <= .001; Eta = 0.198-0.360) between both
      groups, pain intensity (at A1), ROM (at A1, A2, and A3), and functionality (at
      A2, A3, and A4) were increased. Nevertheless, the rest of measurements did not
      show significant differences (P > .05). CONCLUSION: Quadriceps vastus medialis
      TrP-DN in conjunction with a rehabilitation protocol in subacute patients with
      surgical reconstruction of complete ACL rupture increases ROM (short-term) and
      functionality (short- to mid-term). Although there was an increase in pain
      intensity with the addition of TrP-DN, this was not detected beyond immediately
      after the first treatment. Furthermore, stability does not seem to be modified
      after TrP-DN.

PMID- 28445291
TI  - Efficacy of sevoflurane as an adjuvant to propofol-based total intravenous
      anesthesia for attenuating secretions in ocular surgery.
AB  - BACKGROUND: The incidence of nasal secretions into the operative field is as high
      as 5% in ophthalmic surgery under general anesthesia. It may induce postoperative
      endophthalmitis. Secretions under propofol-based total intravanous anesthesia
      (TIVA) are greater than sevoflurane anesthesia during surgery. Postoperative
      nausea and vomiting (PONV) after inhalational anesthesia is higher than TIVA and
      may increase intraocluar pressure. We investigated the effect of sevoflurane
      combination with propofol-based TIVA on nasopharyngeal secretions and PONV in
      ocular surgery. METHODS: Fifty patients undergoing ocular operations were
      randomly assigned for propofol-based TIVA or propofol/sevoflurane anesthesia. In
      the TIVA group (n = 25), anesthesia was induced and maintained with propofol and
      fentanyl; in the propofol/sevoflurane group (n = 25), 1% sevoflurane anesthesia
      was added. RESULTS: Nasopharyngeal excretion volume was significantly higher in
      the propofol-based TIVA group than in the propofol/sevoflurane group (31.0 +/-
      18.1 vs 13.7 +/- 12.6 ml; P < .001). No significant difference in extubation time
      was noted (propofol-based TIVA: 6.4 +/- 3.6 vs propofol/sevoflurane: 7.4 +/- 3.0
      minutes; P = .34). No postoperative endophthalmitis or PONV in both groups was
      observed. CONCLUSION: Sevoflurane attenuated secretions under propofol-based TIVA
      and did not increase the incidence of PONV or prolonged extubation in ocular
      surgery.

PMID- 28445292
TI  - Prognostic value of immunoscore to identify mortality outcomes in adults with HBV
      related primary hepatocellular carcinoma.
AB  - This study aimed to determine if the immunoscore (IS) staging system would be a
      potential prognostic factor in hepatitis B virus-related hepatocellular carcinoma
      (HBV-HCC) in China.IS was performed in a consecutive cohort of HBV-HCC patients
      (n= 92). CD3+, CD8+, and CD45RO+ T cells were quantified by immunohistochemical
      analyses. The patients were stratified into 5 IS groups: I0, I1, I2, I3, I4 for
      every 2 cell phenotypes (IS1 (CD8/CD45RO, IS2 (CD3/CD8), and IS3 (CD3/CD45RO),
      respectively. ImagePro Plus software was used in the calculation of the paraffin
      embedded tumor sections.The staining of CD3+, CD8+, and CD45RO+ cells in the HBV
      HCC tissue demonstrated that there were higher density and larger area of
      lymphocytes in the invasive margins (IM) region than in the center (CT).
      Univariate analysis showed that preoperative TNM staging (P = .01), serum gamma
      glutamyl transpeptidase (GGT) level (P = .03), vascular invasion (P = .00), and
      density of CD3+T (CT) (P = 0.01) were correlated significantly with disease-free
      survival (DFS); serum alpha-fetoprotein (AFP) level (P = .02), tumor size (P =
      .00), serum cholinesterase (CHE) (P = .04), and GGT level (P = .01), density of
      CD3+T(CT) (P = .00), CD8+T(CT)(P = .00), CD45RO+T(CT) (P = .00), and CD45RO+T
      (IM) (P = .02) were correlated with overall survival (OS). Multivariate analysis
      showed that TNM staging was not an independent prognostic factor of DFS and OS.
      Our results showed ISs did not have a significantly correlation with DFS (P =
      .35, .19, and .07, respectively), but it was correlated significantly with OS (P
      = .00, .00, and .00, respectively). There were statistical differences among the
      OS of every ISs subgroup except I0 and I1 by the Cox regressions analysis.The IS
      staging was closely related to the outcome of patients. It can compensate the TNM
      tumor classification system in predicting the prognosis of HBV-HCC patients.

PMID- 28445293
TI  - Possible pathways used to predict different stages of lung adenocarcinoma.
AB  - We aimed to find some specific pathways that can be used to predict the stage of
      lung adenocarcinoma.RNA-Seq expression profile data and clinical data of lung
      adenocarcinoma (stage I [37], stage II 161], stage III [75], and stage IV [45])
      were obtained from the TCGA dataset. The differentially expressed genes were
      merged, correlation coefficient matrix between genes was constructed with
      correlation analysis, and unsupervised clustering was carried out with
      hierarchical clustering method. The specific coexpression network in every stage
      was constructed with cytoscape software. Kyoto Encyclopedia of Genes and Genomes
      pathway enrichment analysis was performed with KOBAS database and Fisher exact
      test. Euclidean distance algorithm was used to calculate total deviation score.
      The diagnostic model was constructed with SVM algorithm.Eighteen specific genes
      were obtained by getting intersection of 4 group differentially expressed genes.
      Ten significantly enriched pathways were obtained. In the distribution map of 10
      pathways score in different groups, degrees that sample groups deviated from the
      normal level were as follows: stage I < stage II < stage III < stage IV. The
      pathway score of 4 stages exhibited linear change in some pathways, and the score
      of 1 or 2 stages were significantly different from the rest stages in some
      pathways. There was significant difference between dead and alive for these
      pathways except thyroid hormone signaling pathway.Those 10 pathways are
      associated with the development of lung adenocarcinoma and may be able to predict
      different stages of it. Furthermore, these pathways except thyroid hormone
      signaling pathway may be able to predict the prognosis.

PMID- 28445294
TI  - Unilateral versus bilateral percutaneous kyphoplasty for osteoporotic vertebral
      compression fractures: A meta-analysis.
AB  - BACKGROUND: The debate on the efficacy of unilateral percutaneous kyphoplasty
      (UPKP) and bilateral percutaneous kyphoplasty (BPKP) for the treatment of
      osteoporotic vertebral compression fractures (OVCFs) is ongoing.This meta
      analysis aimed to evaluate the clinical results of UPKP and BPKP in the treatment
      of OVCFs. METHODS: Web of Science, PubMed, Embase, and the Chinese Biomedical
      Database publication databases were searched using a date range of January 2008
      to November 2016, for studies comparing UPKP and BPKP for the treatment of OVCFs.
      The clinical effectiveness was assessed by comparing perioperative outcomes
      (surgery time, the volume of injected cement, X-ray exposure time, and kyphotic
      angle reduction), clinical outcomes (visual analogue scale [VAS] for pain relief
      and Oswestry Disability Index [ODI] for quality of life), and surgery-related
      complications (cement leakage and adjacent vertebral fractures). Data were
      analyzed using Stata/SE11.0 software. RESULTS: Fourteen trials with 1194 patients
      were retrieved. The pooled results showed significant differences in surgery time
      (weighted mean difference [WMD] -21.44, 95% confidence interval [CI] [-23.57 to 
      19.30]; P < .001); volume of injected cement [WMD -1.90, 95% CI [-2.26 to -1.54);
      P < .001); and X-ray exposure time (WMD -13.66, 95%CI [-19.59 to -7.72]; P <
      .001) between UPKP and BPKP treatments. However, the pooled results showed no
      significant differences in kyphotic angle reduction, VAS in the short-term, VAS
      in the long-term, ODI, cement leakage, or adjacent vertebral fractures between
      the 2 surgical procedures. Following a subgroup analysis, the results based on
      randomized controlled trials (RCTs) indicated that there were significant
      differences in surgery time (WMD -24.65, 95%CI [-26.53 to -22.77]; P < .001) and
      the volume of injected cement (WMD -1.66, 95%CI [-1.97 to -1.36]; P < .001)
      between UPKP and BPKP treatment procedures, respectively. The results based on
      RCTs indicated that there were no significant differences, either in kyphotic
      angle reduction or in X-ray exposure time, between the 2 surgical procedures.
      CONCLUSIONS: Compared to BPKP procedures, UPKP procedures may achieve similar
      clinical results in the treatment of OVCFs when assessed in terms of the pain
      relief, improvements in life quality, and surgery-related complications. However,
      UPKP procedures had a shorter operation time and volume of injected cement
      compared with BPKP procedures. Additional high quality and multicenter RCTs are
      needed to provide further robust evidence.

PMID- 28445295
TI  - Metastatic breast cancer to the rectum: A case report with emphasis on MRI
      features.
AB  - RATIONALE: Less than 1% of breast carcinomas metastasize to the gastrointestinal
      tract. The diagnosis is frequently not recognized especially when the history of
      breast carcinoma is remote. PATIENT CONCERNS: A 61-year-old female with a remote
      history of breast carcinoma presented with a 3-month history of change in bowel
      habits. Colonoscopy showed a circumferential rectal mass with initial impression
      of primary rectal cancer. MRI of the rectum showed findings that are atypical for
      primary rectal cancer. DIAGNOSES: Deep biopsy of the rectal mass confirmed
      lobular breast carcinoma metastasis to the rectum. INTERVENTION AND OUTCOMES: The
      patient was treated with radiotherapy and hormonal therapy. She is
      symptomatically well 2 years after presentation and remains on hormonal therapy.
      LESSONS: Lobular breast cancer which metastasizes to the rectum can mimic primary
      rectal cancer clinically. The unique MRI features described in our case when
      present with a concordant history of lobular breast carcinoma should alert the
      radiologist to the possibility of this diagnosis which has important treatment
      implications.

PMID- 28445296
TI  - A case of cerebral hyperperfusion following spontaneous recanalization of
      occluded middle cerebral artery: Reperfusion injury or true cerebral
      hyperperfusion syndrome?
AB  - BACKGROUND: Cerebral hyperperfusion syndrome (CHS) and reperfusion injury are
      distinct pathological phenomena. CASE SUMMARY: We present the case of a young
      ischemic stroke patient with middle cerebral artery (MCA) occlusion and
      spontaneous recanalization. Follow-up transcranial Doppler ultrasound showed high
      velocity flow in the left MCA, and neuroimaging revealed infarction, brain edema,
      artery dilatation, and hyperperfusion, consistent with both CHS and reperfusion
      injury. CONCLUSION: In cases with signs of both CHS and reperfusion injury, we
      speculate that CHS may be both a contributor to and a manifestation of
      reperfusion injury.

PMID- 28445297
TI  - The efficacy of radiation therapy in adrenocortical carcinoma: A propensity score
      analysis of a population-based study.
AB  - Adrenocortical carcinoma (ACC) is a rare and malignant tumor. The main treatment
      is primary surgical resection with or without mitotane therapy. The role of
      radiation therapy is still controversial. We aim to investigate the survival
      efficacy of radiotherapy in a large population-based cohort.We queried the
      Surveillance, Epidemiology, and End Results (SEER) database (1973-2013) to
      identify cases with ACC. Traditional multivariate Cox regression and propensity
      score analysis were used to evaluate the effect of radiotherapy on cancer
      survival. The survival outcomes included overall survival and cancer-specific
      survival. The treatment effect was evaluated using a hazard ratio (HR) and its
      95% confidence interval (95% CI).Five hundred thirty patients diagnosed with ACC
      were identified. Among them, 74 patients received radiotherapy. In the
      multivariate Cox regression, radiotherapy did not increase the overall survival
      (HR 0.794, 95% CI 0.550-1.146, P = .218) or cancer-specific survival (HR 0.842,
      95% CI 0.574-1.236, P = .388). In the propensity score analysis, the results
      consistently showed no survival benefit of radiotherapy regardless of the
      different propensity score analysis methods.Radiotherapy did not improve overall
      or cancer-specific survival in ACC patients. Further confirmation is needed from
      multi-institutional prospective studies in the future.

PMID- 28445298
TI  - Barcelona clinic liver cancer-stage C hepatocellular carcinoma: A novel approach
      to subclassification and treatment.
AB  - Barcelona clinic liver cancer-stage C (BCLC-C) encompasses a broad spectrum of
      tumor burdens, liver function statuses, patient prognoses, and treatment
      strategies. Currently, sorafenib is the only recommended treatment for patients
      with BCLC-C and outcomes remain suboptimal. The aims of this study were to assess
      the heterogeneity of BCLC-C hepatocellular carcinoma (HCC) cases, propose a novel
      subclassification for these cases, and suggest optimal treatment strategies other
      than sorafenib.We retrospectively analyzed 196 consecutive BCLC-C HCC patients
      who were diagnosed and treated between January 2008 and December 2015.All 196
      patients were classified according to the modified Union for International Cancer
      Control (Stage I, 0.0%; Stage II, 8.2%; Stage III, 64.3%; Stage IVA, 21.9%; and
      Stage IVB, 5.6%) and American Joint Committee on Cancer TNM staging systems
      (Stage I, 0.0%; Stage II, 16.3%; Stage IIIA, 27.6%; Stage IIIB, 49.5%; Stage
      IIIC, 1.5%; Stage IVA, 1.0%; and Stage IVB, 4.1%). First-line treatment
      modalities included surgical resection (8.7%), transarterial chemoembolization
      (49.5%), hepatic arterial infusion therapy (5.6%), sorafenib therapy (9.2%),
      radiotherapy (9.2%), and best supportive care (10.7%). In univariate analysis,
      Child-Pugh score, tumor size, distant metastasis, multinodular or
      infiltrative/diffuse type of HCC, main portal vein invasion, hepatic vein
      invasion, and bile duct invasion were significantly associated with survival (P <
      .001). Tumor size, distant metastasis, HCC type, and bile duct invasion remained
      significantly associated with 1-, 3-, and 5-year survival rates in multivariate
      Cox regression analyses. Using these 4 characteristics, a novel subclassification
      of BCLC-C was developed and applied to the patient cohort. The subclassification
      included 5 substages (stages C0-C4), as defined based on the number of
      characteristics that were present in each HCC case (0-4). The subclassification
      showed significant associations with survival, with median survival times of 3026
      days, 605 days, 224 days, 126 days, and 82 days for patients with Stage C0, C1,
      C2, C3, and C4 disease, respectively (P < .001). Additionally, diverse survival
      rates were observed when different treatment modalities were selected for cases
      within each substage.The proposed BCLC-C subclassification of HCC patients is
      effective in providing better prognostic subclassifications and more appropriate
      treatment strategies.

PMID- 28445299
TI  - Endoscopic ultrasonography predicts early esophageal variceal bleeding in liver
      cirrhosis: A case report.
AB  - RATIONALE: Bleeding esophageal and gastric varices constitute a serious
      complication in liver cirrhosis. Previous studies have shown that endoscopic
      ultrasonography (EUS) can be used to predict early esophageal variceal bleeding
      in liver cirrhosis. PATIENT CONCERNS: We report a case of a 46-year-old man with
      hepatitis B liver cirrhosis (CTP score, 5; Child-Pugh class, A) who was admitted
      to our hospital due to a decreased appetite lasting 1 week. DIAGNOSIS: He was
      initially diagnosed with decompensated hepatitis B cirrhosis; an abdominal
      computed tomography (CT) scan indicated a diagnosis of liver cirrhosis and portal
      hypertension (PHT). INTERVENTIONS: Common endoscopic examination showed no
      evidence of gastroesophageal varices; EUS revealed distinct varices of the
      esophageal and gastric veins. Six months after discharge, the patient was
      rehospitalized because of upper gastrointestinal bleeding. Endoscopic ligation
      was implemented as well as esophageal varices loop ligature (EVL). OUTCOMES: Six
      months later, EUS showed obvious collateral and perforator veins. LESSONS: We
      should strongly recommend that patients with liver cirrhosis undergo EUS in
      addition to a routine endoscopic examination. EUS can play an important role in
      evaluating the risk for bleeding in PHT and can be used to assess the efficacy of
      EVL.

PMID- 28445300
TI  - Malignant phosphaturic mesenchymal tumor with pulmonary metastasis: A case
      report.
AB  - RATIONALE: Phosphaturic mesenchymal tumor (PMT) is a new tumor entity of soft
      tissue and bone tumor recently accepted by the World Health Organization, which
      typically causes the paraneoplastic syndrome of tumor-induced osteomalacia (TIO).
      The majority of PMTs follow a benign clinical course and local recurrence occurs
      in < 10% of cases, malignant PMTs with distant organ metastasis are extremely
      uncommon. PATIENT CONCERNS: We reported a 41-year-old woman who was diagnosed
      with PMT 10 years ago with a repeated recurrence and pulmonary metastasis.
      DIAGNOSES: Based on clinical manifestations, MRI scan, serum biochemical
      indicators evaluation, followed by histopathological examination, the patient was
      diagnosed as malignant PMT with pulmonary metastasis. INTERVENTIONS: The patient
      was treated with calcium, phosphorus, and vitamin D after surgical resection and
      measured the serum ion concentrations every 3 months. OUTCOMES: The patient had a
      favorable outcome for 10 months without recurrence. LESSONS: PMTs lack of
      characteristic histological morphology, some recurrence cases may appear benign
      morphologically; the malignant PMTs are easily overlooked. Patients with PMT
      should be carefully evaluated and monitored, in order to early identify its
      malignant potential.

PMID- 28445301
TI  - The value of red cell distribution width in patients with ovarian cancer.
AB  - BACKGROUND: The red cell distribution width (RDW) has attracted attention in the
      diagnosis of malignant tumors. In this study, we analyzed the correlation between
      the RDW and ovarian cancer by observing changes in the RDW in patients with
      ovarian cancer. METHODS: Patients diagnosed with ovarian cancer at the First
      Affiliated Hospital of Guangxi Medical University, China, from 2012 to 2016, were
      retrospectively analyzed. Patients diagnosed with ovarian benign tumors in our
      hospital during the same period comprised the control group. Differences in
      relevant indicators were compared between the ovarian cancer and control groups
      using the Mann-Whitney U test. Differences in the RDW at different stages of
      ovarian cancer were compared using one-way analysis of variance. Correlations
      between the RDW and experimental parameters in patients with ovarian cancer were
      analyzed by Spearman correlation. RESULTS: The RDW, absolute neutrophil count
      (N), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR),
      and cancer antigen 125 (CA-125) concentration were significantly higher in the
      ovarian cancer than control group. The hemoglobin concentration (Hb) and absolute
      lymphocyte count (L) were significantly lower in the ovarian cancer than control
      group. The RDW was significantly different among 4 different stages of ovarian
      cancer. Correlation analysis demonstrated that the RDW was negatively correlated
      with the hemoglobin concentration (Hb). The RDW was positively correlated with
      the cancer stage, NLR, PLR, and CA-125 concentration. The area under the receiver
      operating characteristic curve of the RDW was 0.876 (95% confidence interval
      0.829-0.923). CONCLUSION: The RDW is associated with ovarian cancer and is a
      potential marker of its progression.

PMID- 28445302
TI  - Cholestasis caused by panhypopituitarism and acquired cytomegalovirus infection
      in a 2-month-old male infant: A case report.
AB  - RATIONALE: Septo-optic dysplasia (SOD) is a rare congenital disorder that may
      cause jaundice in infants. However, it is usually prone to neglect and
      misdiagnosis in infants with cholestasis because endocrine disorder such as
      panhypopituitarism is rare in the cause of infantile cholestasis. We report a
      case of SOD concurrent with acquired cytomegalovirus (CMV) infection, who
      presented with prolonged jaundice as the first clinical sign. PATIENT CONCERNS:
      The patient was a 2-month-old male infant who presented with cholestasis,
      combined with fever and panhypopituitarism. DIAGNOSES: He was diagnosed with SOD
      and acquired CMV infection. INTERVENTIONS: He was treated with hormone
      replacement therapy and ganciclovir. OUTCOMES: After correction of the pituitary
      hormone deficiency and ganciclovir treatment, significant improvements of
      cholestasis, retinal lesions, and growth rate were seen in our patient. LESSONS:
      Although an endocrine disorder such as panhypopituitarism is rare in the cause of
      neonatal or infantile cholestasis, we must keep this reason in mind.

PMID- 28445303
TI  - Lifetime and recent alcohol use and bone mineral density in adults with HIV
      infection and substance dependence.
AB  - Low bone mineral density (BMD) is common in people living with HIV infection
      (PLWH), increasing fracture risk. Alcohol use is also common in PLWH and is a
      modifiable risk factor for both HIV disease progression and low BMD. In PLWH,
      alcohol's effect on BMD is not well understood.We studied adult PLWH with
      substance dependence. We measured lifetime alcohol use (kg) and recent (i.e.,
      past 30-day) alcohol use (categorized as: abstinent, low risk, or high risk). In
      adjusted multivariable regression analyses, we tested associations between
      lifetime and recent alcohol use and (i) mean BMD (g/cm) at the femoral neck,
      total hip, and lumbar spine and (ii) low BMD diagnosis (i.e., osteopenia or
      osteoporosis). We also examined associations between 2 measures of past alcohol
      use (i.e., total consumption [kg] and drinking intensity [kg/year]) and BMD
      outcome measures during 3 periods of the HIV care continuum: (i) period before
      first positive HIV test, (ii) period from first positive HIV test to
      antiretroviral therapy (ART) initiation, and (iii) period following ART
      initiation.We found no significant associations between lifetime alcohol use and
      mean femoral neck (beta -0.000, P = .62), total hip (beta -0.000, P = .83) or
      lumbar spine (beta 0.001, P = .65) BMD (g/cm), or low BMD diagnosis (adjusted
      odds ratio [aOR] = 0.98, 95% Confidence Interval [CI]: 0.95-1.01). There was no
      significant correlation between past 30-day alcohol use and mean BMD (g/cm). Past
      30-day alcohol use was associated with low BMD diagnosis (P = .04); compared to
      abstainers, the aOR for high risk alcohol use was 1.94 (95% CI: 0.91-4.12), the
      aOR for low risk alcohol use was 4.32 (95% CI: 1.30-14.33). Drinking intensity
      (kg/year) between first positive HIV test and ART initiation was associated with
      lower mean BMD (g/cm) at the femoral neck (beta -0.006, P = .04) and total hip
      (beta -0.007, P = .02) and increased odds of low BMD (aOR = 1.18, 95% CI = 1.03
      1.36).In this sample of PLWH, we detected no association between lifetime alcohol
      use and BMD. However, recent drinking was associated with low BMD diagnosis, as
      was drinking intensity between first positive HIV test and ART initiation.
      Longitudinal studies should confirm these associations.

PMID- 28445304
TI  - Toll-like receptors-2 and -9 (TLR2 and TLR9) gene polymorphism in patients with
      type 2 diabetes and diabetic foot.
AB  - Toll-like receptors (TLRs) are innate immune receptors that mediate the
      inflammatory response in diabetes mellitus (DM). The aim of this study is to
      evaluate the association of TLR2 and TLR9 gene polymorphism in patients with type
      2 DM (T2DM) and diabetic foot (DF).The study included 90 subjects divided into
      group I (30 patients with T2DM and DF), group II (30 patients with T2DM and no
      evidence of DF), and group III (normal control subjects). TLR2 (1350 T/C,
      rs3804100) and TLR9 (1237 T/C, rs5743836) genotyping was performed by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for
      all subjects.There was a statistically significant difference in the distribution
      of TLR9-1237 T/C genotypes between groups I and II (P < .029) as well as between
      groups I and III (P < .001). Calculated risk estimation revealed that TLR9-1237
      polymorphism conferred almost 20 times increased risk of DF disorders in T2DM (OR
      = 20, 95% CI = 5.38-74.30). There was no statistical difference in the
      distribution of TLR2-1350T/C genotypes between the 3 groups.TLR9-1237 T/C gene
      polymorphism may be considered as a molecular risk for DF among patients with
      T2DM.

PMID- 28445305
TI  - A case report of painless type A aortic dissection with intermittent convulsive
      syncope as initial presentation.
AB  - RATIONALE: The initial presenting symptoms and signs of acute aortic dissection
      are so diverse that it makes early and accurate diagnosis arduous. Painless and
      convulsive syncope due to cardiac arrhythmia were not typical presentations of
      acute aortic dissection. PATIENT CONCERNS: A 61-year-old male presenting with
      transient consciousness loss and suspected seizure attack was sent to emergency
      room (ER) by ambulance. Consciousness loss accompanying with upward gaze and limb
      convulsion was noted in ER, and electrocardiogram monitor recorded a transient
      cardiac asystole then spontaneous recovery of sinus rhythm. DIAGNOSES: Chest X
      ray revealed widening of the mediastinum. Subsequently, contrast-enhanced chest
      computed tomography demonstrated Stanford type A aortic dissection. LESSONS: To
      the authors' knowledge, this is the first reported case that cardiac asystole may
      be related to painless type A aortic dissection and then leading to convulsive
      syncope as presenting symptoms.

PMID- 28445306
TI  - The efficacy and safety of epinephrine for postoperative bleeding in total joint
      arthroplasty: A PRISMA-compliant meta-analysis.
AB  - BACKGROUND: Total joint arthroplasty (TJA) usually results in postoperative
      bleeding. Some randomized controlled trials (RCTs) and nonrandomized controlled
      trials (non-RCTs) have been performed to evaluate the effects of epinephrine on
      postoperative bleeding after TJA. However, this remained controversial about the
      efficacy and safety of epinephrine for postoperative bleeding in TJA. The
      objective of our meta-analysis was to compare the overall effect and safety of
      epinephrine and placebo for postoperative bleeding in TJA. METHODS: PubMed,
      Embase, and the Cochrane Library were searched to identify potentially relevant
      articles. RCTs or non-RCTs involving epinephrine and placebo for blood loss in
      total knee arthroplasty or total hip arthroplasty were included. Our study was
      performed based on the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses statement. RevMan v5.3 was used to analyze the relevant data. RESULTS:
      Four RCTs and 1 non-RCT involving 646 participants met the inclusion criteria.
      The overall pooled results from meta-analysis demonstrated that compared with
      control groups, epinephrine groups could significantly reduce the postoperative
      bleeding volume (mean difference [MD] = -168.42, 95% confidence interval [CI]: 
      272.37 to -64.47, P = 0.001). There was no significant difference in
      intraoperative bleeding volume between epinephrine and control groups (MD = 
      12.89, 95% CI: -53.45 to 27.69, P = 0.53). No significant difference was found
      between 2 groups in terms of postoperative hemoglobin loss (MD = -0.28, 95% CI: 
      0.66 to 0.10, P = 0.15). Compared with the control groups, no statistically
      significant difference was found in terms of postoperative transfusion rate in
      epinephrine groups (relative risk [RR] 0.86, 95% CI: 0.64-1.15, P = 0.31). In
      addition, the results of the meta-analysis also indicated no significant
      difference in terms of the incidence rate of deep venous thrombosis (DVT) between
      2 groups (RR 0.28, 95% CI: 0.05-1.64, P = 0.16). CONCLUSION: The meta-analysis
      showed that epinephrine could significantly reduce postoperative bleeding volume
      in TJA without increasing the incidence of DVT. However, there was no significant
      reduction in intraoperative bleeding volume, postoperative hemoglobin loss, and
      transfusion rate after the administration of epinephrine. LIMITATIONS: In this
      study, a higher heterogeneity and a risk of selection bias may be present in
      postoperative hemoglobin loss. In addition, the sample size of the included
      studies was too small, so our findings need to be further validated with more
      high-quality and larger scale RCTs in the future. SYSTEMATIC REVIEW REGISTRATION
      NUMBER: None.

PMID- 28445307
TI  - Alteration of serum high-mobility group protein 1 (HMGB1) levels in children with
      enterovirus 71-induced hand, foot, and mouth disease.
AB  - Hand, foot, and mouth disease (HFMD) is a common pediatric disease caused by
      enterovirus infection. It typically presents as a fever along with flat,
      discolored spots and bumps on the hands, feet, and mouth. Compared with other
      viruses, enterovirus 71 (EV71)-induced HFMD is more prone to cause severe
      complications in children, such as brainstem encephalitis, cardiopulmonary
      disorders, and even death. More in-depth studies are still necessary to
      understand the characteristics of EV71-induced HFMD, although some related
      research has been reported so far. High-mobility group box 1 (HMGB1) is an
      inflammatory cytokine that can upregulate other inflammatory factors through its
      receptors, such as Toll-like receptors and the receptor for advanced glycation
      endproducts.We prospectively investigated the alteration of serum HMGB1,
      interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha levels before and after
      treatment in 82 children with HFMD.We found that the serum HMGB1, IL-6, and TNF
      alpha levels were significantly increased in EV71-induced HFMD, and that these
      changes were more serious in the severe and critical HMFD groups; however, there
      was no significant difference in the HMGB1 level between the normal control and
      mild HMFD groups. Moreover, the serum HMGB1 level was positively correlated with
      the alteration of serum IL-6 and TNF-alpha concentrations.These results suggest
      that HMGB1 is involved in the inflammatory pathogenesis of EV71-induced HFMD and
      that the serum level of HMGB1 could be applied as a clinical indicator for the
      severity of HFMD, and also a sign for the recovery prognosis of HFMD.

PMID- 28445309
TI  - Exploring spatial patterns of acupoint indications from clinical data: A STROBE
      compliant article.
AB  - Every acupoint has specific indications for acupuncture treatment. These
      indications, primarily established based on the meridian system, have spatial
      patterns of symptoms on the human body. We investigated the associations between
      acupoints and symptom locations in 75 patients with chronic pain who were asked
      to sketch the localization of their symptoms on body schemes using the bodily
      sensation map (BSM) system. Combining the BSM and clinical information, we
      estimated the statistical parameters of relationships between acupoints and
      spatial information on symptoms. We further visualized spatial patterns of
      indications of the representative acupoints on the human body template using a Z
      score. Using a statistical parametric map method, we observed significant
      activation patterns of 12 acupoint indications with spatial patterns. The 1st
      group of patterns was distant from the acupoint locus and was strongly associated
      with the route of the corresponding meridian. The 2nd group was found around the
      acupoint locus, the majority of which was located at the trunk or back areas.
      Intensive investigations of the spatial patterns of acupoint indications would be
      a novel paradigm to explain point specificity of acupuncture treatment based on
      the original concept of the meridian system. Future studies should include more
      meaningful clinical data with larger sample sizes.

PMID- 28445308
TI  - Clinical value of radionuclide shuntography by qualitative methods in
      hydrocephalic adult patients with suspected ventriculoperitoneal shunt
      malfunction.
AB  - To determine the clinical value of radionuclide shuntography in the evaluation of
      adult hydrocephalic patients with suspected ventriculoperitoneal (V-P) shunt
      malfunction. All adult patients who underwent Tc-99m diethylenetriamine
      pentaacetic acid shuntographic scans at Far Eastern Memorial Hospital between
      August 2005 and December 2015 were included. Shuntographic results were visually
      evaluated in a simple qualitative manner: prompt flow that reached the peritoneum
      on 30-minute early images and diffuse peritoneal tracer distribution on 2-hour
      delayed images were interpreted as nonobstructive shunt flow. Partial dysfunction
      was diagnosed as scintigraphic findings between no obstruction and complete
      obstruction (where complete malfunction indicated no peritoneal distribution on
      delayed images). The results were correlated with the clinical outcomes and
      surgical results within 30 days. Diagnostic sensitivity (Se), specificity (Sp),
      positive predictive value (PPV), negative predictive value (NPV), and overall
      accuracy were also calculated. A total of 93 scans in 69 patients with suspected
      V-P shunt malfunction were analyzed. Sixty-two scans were interpreted as
      abnormal, including complete (n = 26, 41.9) distal obstruction, partial (n = 35,
      56.5) distal dysfunction, and miscellaneous (n = 1, 1.6, cerebrospinal fluid
      leak). The Se and Sp were 83.0% and 55.0%, respectively, and PPV, NPV, and
      accuracy were all 71.0%. Twenty-five patients (28 scans) underwent surgical
      revision, and the results were highly concordant with the imaging findings (Se,
      92.0%; Sp, 100.0%; PPV, 100.0%; NPV, 60.0%; and accuracy, 92.9%). Radionuclide
      shuntography provides useful information in adult patients with V-P shunt
      malfunction and could be used to guide further surgical intervention.

PMID- 28445311
TI  - An observational study on the relationship between serum uric acid and
      hypertension in a Northern Chinese population aged 45 to 59 years.
AB  - Little is known about the relationship serum uric acid (SUA) and hypertension in
      Chinese population. Therefore, the aim of this study was to determine the
      association between SUA and hypertension in a northern Chinese population. The
      participants were a group of 1730 Chinese adults aged 45 to 59 years in Shandong
      Province, who were recruited from the Linyi Nutrition and Health Survey (2015
      2016). Hypertension was defined as systolic blood pressure >=140 mm Hg and/or
      diastolic blood pressure >=90 mm Hg. Hyperuricemia was defined as SUA >420
      MUmol/L (7.0 mg/dL) for men and >360 MUmol/L (6.0 mg/dL) for women. All
      anthropometric measurements and biochemical data were collected following
      standard protocols. Multivariate logistic regression analysis was used to examine
      the association between SUA and hypertension with adjustment of confounding
      variables. Body mass index, waist circumference, waist-to-hip ratio, systolic
      blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides,
      alanine aminotransferase, aspartate aminotransferase, SUA, and the prevalence of
      hypertension and hyperuricemia were significantly higher in males than in females
      (P < .001). The females had significantly higher levels of total cholesterol and
      high-density lipoprotein cholesterol. Besides, after adjustment for confounding
      variables, hyperuricemia was associated with an increased risk of hypertension in
      both male and female patients, with odds ratios of 2.152 (95% confidence interval
      1.324-3.498) and 2.133(95% confidence interval 1.409-3.229),
      respectively.Hyperuricemia was significantly associated with the risk of
      hypertension. Further longitudinal studies and trails are needed to confirm our
      findings.

PMID- 28445312
TI  - Early progression of brain atrophy in patients with anti-N-methyl-D-aspartate
      receptor encephalitis: Case reports.
AB  - BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis responds
      to immunnotherapy, and approximately 80% of patients with this disorder fully
      recover or have only minor sequelae. Brain magnetic resonance imaging (MRI) does
      not show a specific abnormality, but some patients have progressive cerebral
      atrophy. The cerebral atrophy can become reversible after clinical improvement.
      METHODS: We describe 3 patients with diffuse cerebral atrophy (DCA) on serial
      brain MRI. RESULTS: Two women had the typical spectrum of this disorder, and one
      man had mainly psychiatric symptoms. In a woman with an ovarian tumor, DCA was
      reversible and DCA developed within about a half month. In another woman without
      a tumor, DCA was evident within 19 days and had progressed over the course of 4
      years. The titers of anti-NMDAR antibodies in serum and cerebrospinal fluid (CSF)
      initially decreased, and low titers of the antibodies persisted. In a man without
      a tumor, DCA progressed within 14 days, and during this short period, he did not
      receive prolonged treatment with corticosteroids, various antiepileptic agents,
      or propofol, and he was free of seizures and ventilatory support. CONCLUSION: Not
      only a woman but also a man with anti-NMDAR encephalitis can have DCA in the
      early phase of this disorder. However, DCA can be reversible after clinical
      improvements. The early progression of DCA is not necessarily a poor prognostic
      factor.

PMID- 28445310
TI  - Diagnostic accuracy of serum alanine aminotransferase as biomarker for
      nonalcoholic fatty liver disease and insulin resistance in healthy subjects,
      using 3T MR spectroscopy.
AB  - Recognition of the close relationship of nonalcoholic fatty liver disease (NAFLD)
      with diabetes mellitus 2, obesity, metabolic syndrome, and cardiovascular disease
      has stimulated growing interest in NAFLD as a public health problem. Serum
      alanine aminotransferase (ALT) has been proposed as a marker of NAFLD, but levels
      are within the range currently considered "normal" in a large proportion of NAFLD
      subjects.The aim of the study was to determine the diagnostic accuracy of serum
      ALT for identifying individuals with NAFLD, using 3-Tesla (T) magnetic resonance
      spectroscopy (H-MRS).A cross-sectional study was conducted in 129 healthy
      subjects. Liver triglyceride content was quantified by H-MRS. NAFLD was defined
      as liver triglyceride content greater than 5.56%.Liver triglyceride content was
      >5.56% in 79 participants (NAFLD) and lower in the remaining 50 (normal). Serum
      ALT levels correlated positively with liver triglyceride content (r = 0.58, P <
      .001), Homeostatic Model Assessment for Insulin Resistance (r = 0.32, P < .01),
      and fasting insulin (r = 0.31, P < .01), and inversely correlated with
      adiponectin (r = 0.35, P < .01) and high-density lipoprotein cholesterol (r =
      0.32, P < .01). Regression analysis showed that serum ALT was the best predictor
      of NAFLD (P < .01). Optimal serum ALT cut-off to predict NAFLD was 23 IU/L (area
      under receiver-operating characteristic curve: 0.93; sensitivity: 0.94;
      specificity: 0.72).This study shows that serum ALT is a sensitive and accurate
      biomarker of NAFLD if the "normal" ALT value is revised and established at a
      lower level. An ALT threshold of 23 IU/L identified 94% of individuals with NAFLD
      in the present series, using 3-T H-MRS for liver triglyceride quantification.

PMID- 28445313
TI  - Serum apoprotein A1 levels are inversely associated with disease activity in
      gout: From a southern Chinese Han population.
AB  - To analyze the alteration of lipid profile and inflammatory markers in the serum
      of patients with gouty arthritis (GA), the levels of serum lipid profile, C
      reactive protein (CRP), and erythrocyte sedimentation rates (ESRs) were measured
      in the serum of 69 gout patients, 35 patients with rheumatoid arthritis (RA), 23
      patients with ankylosing spondylitis (AS)/spondyloarthropathy (SpA), and 25
      patients with osteoarthritis (OA). The serum levels of apoprotein A1 (Apo-A1)
      were significantly decreased in patients with gout when compared with RA, AS/SpA,
      and OA patients. The serum levels of CRP were significantly increased in gouty
      patients when compared with RA, AS/SpA, and OA patients. Furthermore, the serum
      levels of ESR were significantly increased in patients with gout compared to
      patients with OA. Correlation analysis indicated that the levels of Apo-A1 were
      negatively correlated with serum ESR and CRP (r = -0.475, P < .001; r = -0.380, P
      = .001, respectively) in the patients with GA. Taken together, this study gives
      us a better understanding of the relationships between serum lipid profile and
      inflammatory markers in gout patients.

PMID- 28445314
TI  - BC-PROM: validation of a patient-reported outcomes measure for patients with
      breast cancer.
AB  - Key issues of treatment for patients with breast cancer such as patient
      satisfaction with treatments, compliance, and some side effects are essential for
      evaluating quality of life by patient-reported outcomes in clinical trials. The
      study aimed to develop and evaluate a specific patient-reported measure which
      included physical, psychological, social, and therapeutic domain for assessing
      the survival of patients with breast cancer.The pool of items was drafted after a
      theoretical revision and cognitive interviews with women with breast cancer. The
      draft scale was formed after the adjustment of the items and dimensions, and the
      selected items were submitted to expert's judgments. Five statistical methods
      were used to select these items by 2 validation samples. The final scale was
      administered to a sample of 417 patients from 8 hospitals and 135 controls for
      reliability, validity, and responsive analyses.The final BC-PROM consisted of 52
      items, 13 subdomains, and 4 domains, being developed after preexamination and
      formal examination. Cronbach alpha coefficient was 0.902 and 0.712 for the full
      scale and therapeutic domain. The structural validity results showed that the
      multidimensional measurement of the scale fulfilled expectations. Differences in
      the BC-PROM mean scores were significant between cancer patients and healthy
      participants in 13 subdomains (P < .05), indicating good responsiveness. Among
      the sample survey of patients, the scale copy acceptance rate was 98.2%,
      completion rate 94.6%, and average filling time 10 minutes.The new and reliable
      BC-PROM was developed in patients with breast cancer and applied to clinical
      treatment evaluation and clinical trials for such patients.

PMID- 28445315
TI  - The effect of Timolol 0.5% on the correction of myopic regression after LASIK.
AB  - BACKGROUD: Postlaser in situ keratomileusis (post-LASIK) refractive regression is
      defined as the gradual, partial, or total loss of initial correction that limits
      the predictability, efficiency, and long-term stability of LASIK. Our study
      assesses the effect of Timolol 0.5% on the correction of myopic regression after
      LASIK. METHODS: This prospective, randomized, controlled study included 62 eyes
      of 62 patients with myopic regression of -1.18 +/- 0.86 diopters (D) after myopic
      LASIK. They were randomly assigned into either Group 1 who received Timolol 0.5%
      eye drops for 3 months or Group 2 who received artificial tears as control
      (during treatment). Patients were followed an additional 2 months after cessation
      of eye drops treatment (posttreatment). RESULTS: During treatment in Group 1, as
      the mean true intraocular pressure (IOPT) lowered significantly, regression
      stopped. As the mean IOPT increased significantly posttreatment and returned to
      its pretreatment level, regression recurred. The effective rate of Timolol
      therapy dropped from 62.5% during treatment to 40.6% posttreatment. On the
      contrary in Group 2, although the mean IOPT did not change significantly,
      regression continually happened as time passed. During treatment, the mean IOPT,
      uncorrected visual acuity, spherical equivalent (SE), and corneal refractive
      power showed significant difference between the 2 groups. In Group 1, the
      differences of effective rate of Timolol therapy between each of the 2 subgroups
      of age, gender, preoperative SE (PSE), or pretreatment time (how long we start
      treatment with Timolol post-LASIK) were not statistically significant.
      CONCLUSION: IOP-lowering eye drop Timolol was effective for the correction of
      myopic regression when a 0.5-D or greater myopic shift is detected after LASIK in
      patients regardless of age, gender, PSE, or anytime we started the treatment only
      if regression happened. However, the myopic regression recurred after cessation
      of Timolol treatment.

PMID- 28445316
TI  - Glycosylated hemoglobin levels and clinical outcomes in nondiabetic patients with
      coronary artery disease: A meta-analysis.
AB  - A number of studies assessed the prognostic value of HbA1c level in nondiabetic
      patients with coronary artery disease (CAD). The purpose of this meta-analysis
      was to assess the association between the HbA1c level and clinical outcomes.We
      searched PubMed, EMBASE, MEDLINE, and the Cochrane Library from their inception
      to 10 April 2016. Studies evaluated the outcomes according to HbA1c levels in CAD
      patients without diabetes mellitus were eligible.Twenty studies involving 22,428
      patients were included. In nondiabetic patients with CAD, a high HbA1c level was
      associated with a higher rate of long-term death (odds ratio 1.76, 95% confidence
      interval 1.44-2.16, P < .001), and myocardial infarction (MI, odds ratio 1.69,
      95% confidence interval 1.07-2.67, P = .026), but not a higher rate of early
      deaths (odds ratio 1.08, 95% confidence interval 0.92-1.27, P = .359). These
      findings for death remained the same after sensitivity analyses and the trim and
      fill method, but the risk difference for MI became nonsignificant after
      adjustment for potential publication bias.Elevated HbA1c level increased the
      risks of long-term mortality and MI, but not the risk for early deaths in
      nondiabetic patients with CAD. High-quality large-scale studies with less bias
      are needed to confirm these findings.

PMID- 28445318
TI  - Renal failure caused by a partly calcified aortic aneurysm in a patient with
      dabigatran therapy: A case report.
AB  - RATIONALE: Abdominal aortic aneurysms (AAAs) are mostly asymptomatic. If aortic
      aneurysms become symptomatic, complications include peripheral embolization,
      acute aortic occlusion, and aortic rupture. However, there are also unusual
      complications caused by aortic aneurysms. PATIENT CONCERNS: An 87-old male with
      dabigatran therapy presented with newly developed melena and acute renal failure.
      Radiological imaging revealed an AAA with thrombotic and calcified deposits which
      affected the renal arteries. DIAGNOSES: Gastrointestinal bleeding and
      hypercoagulation caused by renal failure which was triggered in turn due to an
      AAA. INTERVENTIONS: Adapted antihypertensive therapy and initiation of
      simvastatin 40mg once daily as well as antiplatelet therapy with aspirin 50 mg
      once daily due to patient's refusal of any aneurysm intervention. OUTCOME:
      Neither bleeding event nor aneurysm rupture occurred with the adapted
      antihypertensive therapy, simvastatin and aspirin. LESSONS: Nonruptured AAAs can
      cause rare, unusual, and even life-threatening complications depending on their
      size and anatomical position.

PMID- 28445317
TI  - Timing of tourniquet release in total knee arthroplasty: A meta-analysis.
AB  - BACKGROUND: For total knee arthroplasty (TKA), the tourniquet is routinely
      employed for better visualization, less blood loss, and easier cementation.
      However, the time to release tourniquet remains controversial. Therefore, we
      performed current meta-analysis to assess whether releasing tourniquet before
      wound closure is more effective in reducing blood loss than releasing tourniquet
      after wound closure in TKA without an increased risk of complications. METHODS:
      To conduct this meta-analysis, we searched Medline, Embase, Web of science, and
      the Cochrane library up to November 2016, for randomized controlled trials
      comparing tourniquet releasing before and after wound closure in TKA. A meta
      analysis was performed following the guidelines of the Cochrane Reviewer's
      Handbook and the PRISMA statement. Methodological quality of the trials was
      assessed using the Cochrane risk assessment scale. The data of the included
      studies were analyzed using Stata 12.0. RESULTS: Sixteen trials involving 1010
      patients were identified in current meta-analysis. Our meta-analysis demonstrated
      that there were no significant differences in the 2 groups in terms of calculated
      blood loss (weighted mean difference [WMD] = 160.65, 95% confidence interval
      [CI]: -0.2 to 321.49, P = .05), postoperative blood loss (WMD = -45.41, 95% CI: 
      120.11 to 29.29, P = .233),postoperative hemoglobin decline (WMD = 0.16, 95% CI: 
      2.5 to 2.82, P = .905), transfusion volume (WMD = 79.19, 95% CI: -5.05 to 163.44,
      P = .065),transfusion rates (relative risk [RR] = 1.19, 95% CI: 0.95-1.50, P =
      .134), major complications (RR = 0.51, 95% CI: 0.15-1.73, P = .278), and deep
      vein thrombosis (RR = 0.44, 95% CI: 0.14-1.37, P = .157).Compared with the group
      of releasing tourniquet after wound closure, the group of releasing tourniquet
      before wound closure had a higher volume of total blood loss (WMD = 130.96, 95%
      CI: 58.83-203.09, P = .000) and a longer operation time (WMD = 6.56, 95% CI: 3.12
      10.01, P = .000). However, releasing tourniquet before wound closure could reduce
      minor complications (RR = 0.53, 95% CI: 0.34-0.82, P = .004). CONCLUSIONS: On the
      basis of current meta-analysis, the method of releasing tourniquet before wound
      closure could increase total blood loss and operation time; nevertheless, the
      risk of complications decreased. Thus, if patients are in severe anemia
      condition, the tourniquet perhaps should be released after wound closure to
      decrease blood loss. In contrary, releasing tourniquet before wound closure to
      decrease the risk of complications would be a better choice.

PMID- 28445319
TI  - Intraoperative cardiac arrest: A 10-year study of patients undergoing tumorous
      surgery in a tertiary referral cancer center in China.
AB  - Intraoperative cardiac arrest (IOCA) is a lethal complication of noncardiac
      surgery. According to several reports, immediate survival after IOCA is
      approximately 50%. In this study, a retrospective case analysis was performed to
      determine the incidence of IOCA, the potential causes of cardiac arrest, and the
      risk factors of no resuscitation in patients undergoing tumorous surgery.The
      medical records of surgery patients who experienced cardiac arrest during the
      intraoperative period between 2005 and 2014 were reviewed. The general conditions
      of the patients with IOCA were compared between the successfully resuscitated
      group and the unresuscitated group.Fifteen patients with IOCA among 142,853
      patients undergoing tumorous surgery were reviewed during the study period.
      Immediate survival after IOCA was 60%. Hospital survival was 46.7%. The incidence
      of IOCA decreased during 2010 to 2014 when compared with the rate during 2005 to
      2009 (P < .05). The risk factors affecting the success of resuscitation after
      IOCA included American Society of Anesthesiologists Physical Status (ASA PS)
      classification >= III (P < .05) and preoperative tachycardia (heart rate
      >=100/min, P < .05). The methods of anesthesia had no effects on the results of
      resuscitation.The incidence of IOCA in patients undergoing tumorous surgery was
      1.05 per 10,000 anesthesia. The overall mortality of IOCA was 0.56/10,000. The
      frequency of IOCA decreased within 10 years. There was no cardiac arrest
      primarily attributable to anesthesia over this study period. The risk factors
      leading to unsuccessful resuscitation after IOCA were ASA PS classification >=
      III and preoperative tachycardia.

PMID- 28445320
TI  - Risk factors and long-term outcome for postoperative intra-abdominal infection
      after hepatectomy for hepatocellular carcinoma.
AB  - Intra-abdominal infection (IAI) after hepatectomy is an important morbidity.
      Identification of risk factors that could be avoided in the perioperative period
      may reduce the prevalence of IAI after hepatectomy for hepatocelluar carcinoma
      (HCC).Between January 1995 and December 2009, all patients with HCC who underwent
      curative liver resection were evaluated retrospectively. Long-term outcomes were
      compared in IAI patients and non-IAI patients after hepatectomy. Preoperative,
      intraoperative, and tumor-related factors that could be independent factors for
      postoperative IAI were identified.Of 622 patients with HCC, 24 patients (3.9%)
      had IAI after hepatectomy. Both median survival and survival of patients with
      postoperative IAI were shorter than those for non-IAI patients (P < .05). Upon
      univariate analysis followed by multivariate analyses, three independent
      predictors for IAI were identified: weight loss (odds ratio [OR], 3.27; 95%
      confidence interval [CI], 1.17-9.11; P = .024), liver cirrhosis (0.28, 0.12-0.67,
      .004), and operative time >300 minutes (3.44, 1.46-8.12, .005).IAI after
      hepatectomy affects outcome adversely. Preoperative weight loss, liver cirrhosis,
      and operative time >300 minutes are independent predictors of postoperative IAI.

PMID- 28445323
TI  - Examination of the relationship between management and clinician perception of
      patient safety climate and patient satisfaction.
AB  - PURPOSE: The aim of this study was to explore the relationship between managers
      and clinicians' agreement on deeming the patient safety climate as high or low
      and the patients' satisfaction with those organizations. DATA SOURCES/STUDY
      SETTING: We used two secondary data sets: the Hospital Survey on Patient Safety
      Culture (2012) and the Hospital Consumer Assessment of Healthcare Providers and
      Systems (2012). METHODOLOGY/APPROACH: We used ordinary least squares regressions
      to analyze the relationship between the extent of agreement between managers and
      clinicians' perceptions of safety climate in relationship to patient
      satisfaction. The dependent variables were four Hospital Consumer Assessment of
      Healthcare Providers and Systems patient satisfaction scores: communication with
      nurses, communication with doctors, communication about medicines, and discharge
      information. The main independent variables were four groups that were formed
      based on the extent of managers and clinicians' agreement on four patient safety
      climate domains: communication openness, feedback and communication about errors,
      teamwork within units, and teamwork across units. FINDINGS: After controlling for
      hospital and market-level characteristics, we found that patient satisfaction was
      significantly higher if managers and clinicians reported that patient safety
      climate is high or if only clinicians perceived the climate as high.
      Specifically, manager and clinician agreement on high levels of communication
      openness (beta = 2.25, p = .01; beta = 2.46, p = .05), feedback and communication
      about errors (beta = 3.0, p = .001; beta = 2.89, p = .01), and teamwork across
      units (beta = 2.91, p = .001; beta = 3.34, p = .01) was positively and
      significantly associated with patient satisfaction with discharge information and
      communication about medication. In addition, more favorable perceptions about
      patient safety climate by clinicians only yielded similar findings. PRACTICE
      IMPLICATIONS: Organizations should measure and examine patient safety climate
      from multiple perspectives and be aware that individuals may have varying
      opinions about safety climate. Hospitals should encourage multidisciplinary
      collaboration given that staff perceptions about patient safety climate may be
      associated with patient satisfaction.

PMID- 28445321
TI  - Clinical analysis and prognosis of synchronous and metachronous multiple primary
      malignant tumors.
AB  - The aim of this study was to determine the clinical features, treatment factors,
      and prognosis of patients with multiple primary malignant tumors (MPMTs). In
      total, 161 patients with MPMTs at our hospital (The First Affiliated Hospital of
      Xi'an Jiaotong University, Xi'an, Shaanxi, China) were analyzed in this study. We
      found that among 161 patients with MPMTs, 78 (48.4%) patients had synchronous
      tumors and 83 (51.6%) patients had metachronous tumors. Most clinical and
      pathological features were similar in both groups. Most patients with MPMTs were
      men and older patients (>50 years old), and adenocarcinoma was the most frequent
      pathology type. The most frequent location of all MPMTs was the digestive system.
      The leading tumor association was between digestive-digestive tumors, also.
      However, patients with synchronous tumors and MPMTs of the digestive system
      showed a shorter survival time. In the metachronous cancer group, the median
      interval time was 60 months, and a short interval time (<=60 months) was
      associated with a shorter survival time. In addition, survival time was increased
      in the younger age group (<=50 years old) and in patients who accepted surgery
      based comprehensive therapy. However, only interval time (<=60 months) was an
      independent prognostic factor associated with survival for the metachronous
      cancer group. Therefore, careful surveillance and follow-up are especially
      important in these patients.

PMID- 28445322
TI  - Validation of prognostic scores to predict short-term mortality in patients with
      HBV-related acute-on-chronic liver failure: The CLIF-C OF is superior to MELD,
      CLIF SOFA, and CLIF-C ACLF.
AB  - Acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) patients has a
      high short-term mortality. Identification of effective models to predict the
      short-term mortality may enable early intervention and improve patients'
      prognosis. We aim to assess the performance of the CLIF Consortium Organ Failure
      score (CLIF-C OFs), CLIF sequential organ failure assessment score (CLIF-SOFAs),
      CLIF Consortium ACLF score (CLIF-C ACLFs), ACLF grade, and model for end-stage
      liver disease score (MELDs) in predicting the short-term mortality in CHB
      patients with ACLF.Among the 155 consecutive adult patients with liver failure as
      a discharge diagnosis were screened, and all the patients were treated at the
      Department of Infectious Diseases, Huashan Hospital, Fudan University (Shanghai,
      China) from January 2010 to February 2016. The diagnosis of ACLF was based on the
      criteria formalized by the ACLF consensus recommendations of the Asian Pacific
      Association for the Study of the Liver (APASL). Diagnostic accuracy for
      predicting short-term (28-day) mortality was calculated for CLIF-C OFs, CLIF
      SOFAs, CLIF-C ACLFs, ACLF grade, and MELDs in all patients.One hundred fifty-five
      consecutive adult liver failure patients were screened and 85 patients including
      73 males and 12 females were enrolled. Overall, the 28-day transplant-free
      mortality was 32% in all patients, and 100% in those with severe early course
      (ACLF-3). The area under the receiver operating characteristic curve (AUROC) of
      CLIF-C OFs (AUROC: 0.906, P = .0306, compared with MELDs) was higher than those
      of CLIF-SOFAs (AUROC: 0.876), CLIF-C ACLFs (AUROC: 0.858), ACLF grade (AUROC:
      0.857), and MELDs (AUROC: 0.838) for predicting short-term mortality. The cut
      point for baseline CLIF-C OFs in predicting death was 8.5, with 67% sensitivity,
      90% specificity, and AUROC of 0.906 (95% CI: 0.8450-0.9679).The results indicate
      that short-term mortality is high in patients with ACLF and CLIF Consortium Organ
      Failure score is superior to MELD, CLIF SOFA, and CLIF-C ACLF in predicting its
      short-term mortality.

PMID- 28445324
TI  - Nurse practitioner-physician comanagement of primary care patients: The promise
      of a new delivery care model to improve quality of care.
AB  - BACKGROUND: The U.S. primary care system is under tremendous strain to deliver
      care to an increased volume of patients with a concurrent primary care physician
      shortage. Nurse practitioner (NP)-physician comanagement of primary care patients
      has been proposed by some policy makers to help alleviate this strain. To date,
      no collective evidence demonstrates the effects of NP-physician comanagement in
      primary care. PURPOSE: This is the first review to synthesize all available
      studies that compare the effects of NP-physician comanagement to an individual
      physician managing primary care. METHODS: The PRISMA (Preferred Reporting Items
      for Systematic Reviews and Meta-analyses) framework guided the conduct of this
      systematic review. Five electronic databases were searched. Titles, abstracts,
      and full texts were reviewed, and inclusion/exclusion criteria were applied to
      narrow search results to eligible studies. Quality appraisal was performed using
      Downs and Black's quality checklist for randomized and nonrandomized studies.
      RESULTS: Six studies were identified for synthesis. Three outcome categories
      emerged: (a) primary care provider adherence to recommended care guidelines, (b)
      empirical changes in clinical patient outcomes, and (c) patient/caregiver quality
      of life. Significantly more recommended care guidelines were completed with NP
      physician comanagement. There was variability of clinical patient outcomes with
      some findings favoring the comanagement model. Limited differences in patient
      quality of life were found. Across all studies, the NP-physician comanagementcare
      delivery model was determined to produce no detrimental effect on measured
      outcomes and, in some cases, was more beneficial in reaching practice and
      clinical targets. PRACTICE IMPLICATIONS: The use of NP-physician comanagement of
      primary care patients is a promising delivery care model to improve the quality
      of care delivery and alleviate organizational strain given the current demands of
      increased patient panel sizes and primary care physician shortages. Future
      research should focus on NP-physician interactions and processes to isolate the
      attributes of a successful NP-physician comanagement model.

PMID- 28445325
TI  - Doing well by doing good: Evaluating the influence of patient safety performance
      on hospital financial outcomes.
AB  - BACKGROUND: As financial pressures on hospitals increase because of changing
      reimbursement structures and heightened focus on quality and value, the
      association between patient safety performance and financial outcomes remains
      unclear. PURPOSE: The purpose of this study is to investigate if hospitals with
      higher patient safety performance are associated with higher levels of
      profitability than those with lower safety performance. METHODOLOGY/APPROACH:
      Using multinomial logistic regression, we analyzed data from the spring 2014
      Leapfrog Hospital Safety Score and the 2014 American Hospital Association to
      determine the association between Leapfrog Hospital Safety Score performance and
      three dimensions of organizational profitability: operating margin, net patient
      revenue, and operating income. RESULTS: Our findings suggest that improved
      hospital safety scores are associated with a relative risk of being in the top
      versus bottom quartile of financial performance: 5.41 times greater (p < .001)
      for operating margin, 10.98 times greater (p < .001) for net patient revenue, and
      4.03 times greater (p < .001) for operating income. PRACTICE IMPLICATIONS: Our
      findings suggest that improved patient safety performance, as evaluated within
      the Leapfrog Hospital Safety Score, is associated with improved financial
      performance at the hospital level. Targeted focus on patient safety may allow
      hospitals to improve financial performance, maximize scarce resources, and
      generate additional capital to continue to positively evolve care.

PMID- 28445326
TI  - Acceptance in chronic neck pain: associations with disability and fear avoidance
      beliefs.
AB  - Chronic neck pain can result in significant levels of disability. Physiotherapy
      treatments often aim to modify cognitive factors and this approach benefits some,
      but not all, patients. Research from other pain conditions suggests that
      acceptance may be related to disability; however, it is unclear whether these
      associations exist in patients with neck pain. Moreover, it is unclear to what
      extent other cognitive factors are related to acceptance. Feasibly, if these
      factors are related, existing treatments may already be indirectly modifying
      acceptance. The aim of this study was therefore to establish the associations
      between acceptance and disability, and between acceptance and other cognitive
      factors. Cross-sectional data were collected from 149 patients and regression
      analyses were carried out. In the first analysis, disability was the dependent
      variable and the proportion of variance explained by two acceptance subscales
      (activities engagement and pain willingness) was calculated. In the second
      analyses, the acceptance subscales were the dependent variables. Measures of pain
      related fear, catastrophizing and pain vigilance and awareness were entered as
      explanatory variables and the proportion of variance explained was calculated. In
      the first analysis, acceptance explained 18% of variance in disability (P<0.001).
      In the second analysis, cognitive factors explained 7% (P<0.05) of variance in
      activities engagement and 58% (P<0.001) of pain willingness. On this basis,
      treatments that enhance acceptance may reduce disability. Moreover, as cognitive
      factors were strongly related to pain willingness, but not activity engagement,
      alternative treatments may be required to maximize acceptance. Further studies
      are warranted to assess acceptance-based treatments in patients with neck pain.

PMID- 28445327
TI  - Letters.

PMID- 28445330
TI  - A good death.

PMID- 28445332
TI  - Reducing distress and medication use in patients with dementia.

PMID- 28445335
TI  - Nursing care for the patient with a left ventricular assist device.

PMID- 28445334
TI  - Managing hypocalcemia in massive blood transfusion.

PMID- 28445336
TI  - The nurse who could lift.
AB  - This month, we celebrate nurses for their dedication to patient well-being and
      safety. The American Nurses Association has declared National Nurses Week 2017,
      May 6-12, the "Year of the Healthy Nurse." This special Nurses Week tribute
      reminds us that although patient health and safety is the goal of every nurse,
      it's important to remember our own health as well.

PMID- 28445337
TI  - Navigating a poor performance evaluation.

PMID- 28445338
TI  - Double vision: When a dying patient's family member is also a nurse.

PMID- 28445340
TI  - Patients with esophageal achalasia: Keeping them safe.

PMID- 28445339
TI  - Monitoring for drug-induced movement disorders.

PMID- 28445341
TI  - Get the facts about Fusobacterium.

PMID- 28445342
TI  - Understanding Tourette syndrome.

PMID- 28445343
TI  - Discovering my nursing philosophy.

PMID- 28445344
TI  - Online resources for patients with diabetes.

PMID- 28445345
TI  - Drugs to treat dermatologic disorders.

PMID- 28445347
TI  - Discussion: Global Adverse Event Reports of Breast Implant-Associated ALCL: An
      International Review of 40 Government Authority Databases.

PMID- 28445348
TI  - Discussion: U.S. Epidemiology of Breast Implant-Associated Anaplastic Large-Cell
      Lymphoma.

PMID- 28445349
TI  - Surgical Determinants of Patient-Reported Outcomes following Postmastectomy
      Reconstruction in Women with Breast Cancer.
AB  - BACKGROUND: This national prospective cohort study compared the patient-reported
      outcomes of breast cancer patients undergoing postmastectomy autologous
      reconstruction to those who had breast implants, in terms of aesthetic
      appearance; levels of psychological, physical, and sexual well-being; and overall
      satisfaction. METHODS: Of 5063 women who underwent immediate reconstruction (n =
      3349) or delayed reconstruction (n = 1714) between January 1, 2008, and March 31,
      2009, in England, 2923 women who gave informed consent were sent validated,
      procedure-specific, 18-month follow-up questionnaires. Outcome scale scores
      ranged from 0 (poor) to 100 (excellent); multiple linear regression was used to
      adjust scores for patient and treatment characteristics. RESULTS: Two thousand
      two hundred eighty-nine women (78 percent) returned completed questionnaires
      (immediate reconstruction, n = 1528; delayed reconstruction, n = 761). For
      immediate reconstruction, mean overall satisfaction scores for the various
      techniques ranged from 67 to 85 (median, 67 to 93). For delayed reconstruction,
      mean overall satisfaction scores ranged from 70 to 85 (median, 75 to 100). For
      both groups, similar gradients were observed for the other outcome scales across
      techniques. Reconstruction using patients' own tissues tended to have higher mean
      adjusted scores compared with those techniques using implants alone (p < 0.0001
      for aesthetic appearance, psychological well-being, sexual well-being, and
      satisfaction with outcomes for immediate and delayed reconstruction groups).
      CONCLUSIONS: Women who underwent autologous reconstruction tended to report
      greater satisfaction than those who underwent implant reconstruction. These
      results can inform patients of the anticipated outcomes of their selected
      surgery, but further research is required to confirm whether autologous
      reconstruction is superior in general. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, II.

PMID- 28445350
TI  - Shaped versus Round Implants in Breast Reconstruction: A Multi-Institutional
      Comparison of Surgical and Patient-Reported Outcomes.
AB  - BACKGROUND: Since the 2012 approval of shaped implants, their use in breast
      reconstruction has increased in the United States. However, large-scale
      comparisons of complications and patient-reported outcomes are lacking. The
      authors endeavored to compare surgical and patient-reported outcomes across
      implant types. METHODS: The Mastectomy Reconstruction Outcomes Consortium
      database was queried for expander/implant reconstructions with at least 1-year
      postexchange follow-up (mean, 18.5 months). Outcomes of interest included
      postoperative complications, 1-year revisions, and patient-reported outcomes.
      Bivariate and mixed-effects regression analyses evaluated the effect of implant
      type on patient outcomes. RESULTS: Overall, 822 patients (73.5 percent) received
      round and 297 patients (26.5 percent) received shaped implants. Patients
      undergoing unilateral reconstructions with round implants underwent more
      contralateral symmetry procedures, including augmentations (round, 18.7 percent;
      shaped, 6.8 percent; p = 0.003) and reductions (round, 32.2 percent; shaped, 20.5
      percent; p = 0.019). Shaped implants were associated with higher rates of
      infection (shaped, 6.1 percent; round, 2.3 percent; p = 0.002), that remained
      significant after multivariable adjustment. Other complication rates did not
      differ significantly between cohorts. Round and shaped implants experienced
      similar 2-year patient-reported outcome scores. CONCLUSIONS: This prospective,
      multicenter study is the largest evaluating outcomes of shaped versus round
      implants in breast reconstruction. Although recipients of round implants
      demonstrated lower infection rates compared with shaped implants, these patients
      were more likely to undergo contralateral symmetry procedures. Both implant types
      yielded comparable patient-reported outcome scores. With appropriate patient
      selection, both shaped and round implants can provide acceptable outcomes in
      breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 28445351
TI  - Breast Cancer and Reconstruction: Normative Data for Interpreting the BREAST-Q.
AB  - BACKGROUND: The BREAST-Q is a patient-reported outcome instrument used to
      evaluate outcomes in patients undergoing breast cancer surgery and
      reconstruction. Normative values for the BREAST-Q breast cancer modules have not
      been established, limiting data interpretation. METHODS: Participants were
      recruited by means of the Army of Women, an online community of women (with and
      without breast cancer), to complete Mastectomy, Breast Conserving Therapy, and
      Reconstruction preoperative BREAST-Q scales. Inclusion criteria were women aged
      18 years or older without a history of breast surgery or breast cancer. Analysis
      included descriptive statistics, a linear multivariate regression, and a
      comparison of the generated normative data to previously published BREAST-Q
      findings. RESULTS: The BREAST-Q was completed by 1201 women. The mean patient age
      was 54 +/- 13 years, mean body mass index 26 +/- 6 kg/m, and 38 percent (n = 455)
      had a bra cup size of D or greater. Mean +/- SD scores for BREAST-Q scales were
      as follows: Satisfaction with Breasts (58 +/- 18), Psychosocial Well-being (71 +/
      18), Sexual Well-being (56 +/- 18), Physical Well-being-Chest (93 +/- 11), and
      Physical Well-being Abdomen (78 +/- 20). Women with a body mass index of 30 kg/m
      or greater, cup size of D or greater, age younger than 40 years, and annual
      income less than $40,000 reported lower scores. Comparing normative scores to
      published data in breast cancer patients, Satisfaction with Breasts scores were
      higher after autologous reconstruction and lower after mastectomy; Sexual Well
      being scores were lower after mastectomy and breast conserving therapy; and
      Physical Well-being Chest scores were lower after mastectomy, breast conserving
      therapy, and reconstruction. CONCLUSION: These are the first published normative
      scores for the BREAST-Q breast cancer modules and provide a clinical reference
      point for the interpretation of data.

PMID- 28445352
TI  - Consensus Review of Optimal Perioperative Care in Breast Reconstruction: Enhanced
      Recovery after Surgery (ERAS) Society Recommendations.
AB  - BACKGROUND: Enhanced recovery following surgery can be achieved through the
      introduction of evidence-based perioperative maneuvers. This review aims to
      present a consensus for optimal perioperative management of patients undergoing
      breast reconstructive surgery and to provide evidence-based recommendations for
      an enhanced perioperative protocol. METHODS: A systematic review of meta
      analyses, randomized controlled trials, and large prospective cohorts was
      conducted for each protocol element. Smaller prospective cohorts and
      retrospective cohorts were considered only when higher level evidence was
      unavailable. The available literature was graded by an international panel of
      experts in breast reconstructive surgery and used to form consensus
      recommendations for each topic. Each recommendation was graded following a
      consensus discussion among the expert panel. Development of these recommendations
      was endorsed by the Enhanced Recovery after Surgery Society. RESULTS: High
      quality randomized controlled trial data in patients undergoing breast
      reconstruction informed some of the recommendations; however, for most items,
      data from lower level studies in the population of interest were considered along
      with extrapolated data from high-quality studies in non-breast reconstruction
      populations. Recommendations were developed for a total of 18 unique enhanced
      recovery after surgery items and are discussed in the article. Key
      recommendations support use of opioid-sparing perioperative medications, minimal
      preoperative fasting and early feeding, use of anesthetic techniques that
      decrease postoperative nausea and vomiting and pain, use of measures to prevent
      intraoperative hypothermia, and support of early mobilization after surgery.
      CONCLUSION: Based on the best available evidence for each topic, a consensus
      review of optimal perioperative care for patients undergoing breast
      reconstruction is presented. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 28445353
TI  - Discussion: Consensus Review of Optimal Perioperative Care in Breast
      Reconstruction: Enhanced Recovery after Surgery (ERAS) Society Recommendations.

PMID- 28445354
TI  - A Prospective Randomized Trial Comparing the Effects of Lidocaine in Breast
      Reduction Surgery.
AB  - BACKGROUND: Use of dilute epinephrine tumescent solution in breast reduction
      surgery has been shown to significantly decrease operative blood loss without
      increasing perioperative complications. Lidocaine is commonly added to
      epinephrine to decrease postoperative pain. Evidence supporting this practice,
      however, is limited, and lidocaine toxicity has been reported. METHODS: With
      institutional review board approval, patients undergoing bilateral breast
      reduction surgery were assigned to receive either tumescent saline solution with
      epinephrine (1:1 million) (group 1), or tumescent saline solution with
      epinephrine (1:1 million) and lidocaine (0.05%) (group 2). Tumescent solution
      (500 ml) was infiltrated just before skin incision. Wise pattern reduction with
      an inferior pedicle was used in all cases. A nurse in the postanesthesia care
      unit documented immediate postoperative pain and intravenous narcotic use.
      Patients used a survey to record postoperative pain, nausea/vomiting, and
      narcotic use for the first 24 hours. Results were analyzed using analysis of
      variance and logistic regression models. RESULTS: Forty consecutive patients were
      enrolled (20 in each group). There was no statistical difference between groups 1
      and 2 in total intravenous narcotic use (0.89 versus 0.55; p = 0.10), 24-hour
      narcotic use (32.19 versus 29.47; p = 0.71), peak pain scores both in the
      postanesthesia care unit (5.47 versus 4.47; p = 0.24) and 24 hours
      postoperatively surgery (6.44 versus 6.68; p = 0.78), and 24-hour nausea/vomiting
      counts [group 1, OR, 1.11 (p = 0.87); group 2, OR, 1.87 (p = 0.51)]. There were
      no hospital admissions in either group. CONCLUSIONS: The addition of lidocaine to
      tumescent solution does not significantly affect postoperative pain following
      breast reduction surgery. Considering potential risks and added costs, this
      practice may not be of benefit. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      I.

PMID- 28445355
TI  - Subfascial Primary Breast Augmentation with Fat Grafting: A Review of 156 Cases.
AB  - BACKGROUND: Composite breast augmentation with fat grafting and an implant has
      become very popular in the past 5 years. This achieves the core volume projection
      of an implant complemented by the natural appearance and feel of fat. However, no
      study has looked at the complications and reoperation rates of this technique.
      METHODS: A retrospective chart review examined all patients who underwent the
      combined use of an implant and fat grafting for primary breast augmentation.
      RESULTS: The study identified 156 patients between 2007 and 2013. The mean
      patient age was 31.7 years and the average body mass index was 18.85 kg/m. The
      average implant size was 252 cc. Patients received a mean of 126 cc of fat
      (range, 30 to 250 cc) in subcutaneous soft tissue. Follow-up averaged 22.25
      months (range, 1 to 86 months). The total complication rate was 7.7 percent and
      the reoperation rate was 9.94 percent. Baker grade II/III contracture was the
      most common complication [Baker grade II, n = 4 (2.56 percent); Baker grade III,
      n = 2 (2 percent)], followed by infections [n = 2 (1.28 percent)], hematoma [n =
      2 (1.28 percent)], and malrotation [n = 1 (0.64 percent)]. Delayed reoperation
      was performed in nine patients (9.94 percent) after a mean interval of 31.7
      months. Two patients who developed Baker grade III contractures needed surgery to
      correct the problem. Three cases (1.92 percent) required additional fat grafting
      for insufficient soft-tissue coverage. The mean volume of fat reinjection was 170
      cc. CONCLUSIONS: Composite breast augmentation is a valuable, stable, reliable
      technique in breast aesthetic surgery with good, natural-appearing results. It
      provides long-term aesthetic benefits and avoids the submuscular plane. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 28445356
TI  - What Is the Standard Volume to Increase a Cup Size for Breast Augmentation
      Surgery? A Novel Three-Dimensional Computed Tomographic Approach.
AB  - BACKGROUND: Breast augmentation surgery poses many challenges, and meeting the
      patient's expectations is one of the most important. Previous reports equate 100
      cc to a one-cup-size increase; however, no studies have confirmed this between
      commercially available bras. The aim of this study was to identify the volume
      increase between cup sizes across different brands and the relationship with
      implant selection. METHODS: Five bra cup sizes from three different companies
      were analyzed for their volume capacity. Three methods were used to calculate the
      volume of the bras: (1) linear measurements; (2) volume measurement by means of
      water displacement; and (3) volume calculation after three-dimensional
      reconstruction of serial radiographic data (computed tomography). The clinical
      arm consisted of 79 patients who underwent breast augmentation surgery from
      February 1, 2014, to June 30, 2016. Answers from a short questionnaire in
      combination with the implant volume were analyzed. RESULTS: Across all three
      brands, the interval volume increase varied between sizes, but not all were above
      100 cc. There was some variation in the volume capacity of the same cup size
      among the different brands. The average incremental increase in bra cup size
      across all three brands in the laboratory arm was 135 cc. The mean volume
      increase per cup size was 138.23 cc in the clinical arm. CONCLUSIONS: This
      article confirms that there is no standardization within the bra manufacturing
      industry. On the basis of this study, patients should be advised that 130 to 150
      cc equates to a one-cup-size increase. Bras with narrower band widths need 130 cc
      and wider band widths require 150 cc to increase one cup size.

PMID- 28445357
TI  - The Challenges of Augmentation Mastopexy in the Massive Weight Loss Patient:
      Technical Considerations.
AB  - BACKGROUND: Augmentation mastopexy in the massive weight loss population is
      challenging because of poor skin elasticity and lack of inframammary support.
      Despite several large studies of augmentation mastopexy in the literature, few
      data exist regarding this unique patient population. The authors examine early
      postoperative ptosis, implant malposition, and strategies to optimize outcomes.
      METHODS: A retrospective review of massive weight loss patients who underwent
      augmentation mastopexy from 2003 to 2011 was performed to record age, body mass
      index, implant characteristics, postoperative ptosis, and implant malposition.
      RESULTS: Thirty patients were identified with a mean age of 44.8 +/- 8.5 years,
      mean current body mass index of 26.1 +/- 3.9 kg/m, and mean follow-up time of
      283.5 days (range, 7 to 1095 days). Preoperatively, patients mostly presented
      with grade 3 ptosis (63.3 percent). Five patients (16.7 percent) developed
      postoperative ptosis within the first 3 months after surgery, with no increase
      after this time. Implant malposition increased significantly with time: 61.9
      percent by 12 months (p = 0.006), with a median time for implant malposition of
      160 days. Postoperative ptosis was significantly related to age (p = 0.039) and a
      larger left-side implant (p = 0.022). Implant malposition was significantly
      related to higher current body mass index (p = 0.047), but not to implant size.
      Two patients (6.6 percent) underwent revision procedures. CONCLUSION: Massive
      weight loss patients have an increased risk of early postoperative ptosis or
      implant malposition, reinforcing the need for appropriate preoperative counseling
      to manage patient expectations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      IV.

PMID- 28445358
TI  - Discussion: The Challenges of Augmentation Mastopexy in the Massive Weight Loss
      Patient: Technical Considerations.

PMID- 28445359
TI  - The Impact of Body Contouring Procedures on Urologic Outcomes in Massive Weight
      Loss Patients.
AB  - BACKGROUND: Post-massive weight loss body contouring is a growing area of plastic
      surgery. Studies have shown preexisting urinary incontinence amelioration in
      patients undergoing abdominal body-contouring procedures. These studies are
      small, focus on cosmetic abdominoplasties, and lack use of standardized surveys.
      The purpose of this study was to evaluate urinary incontinence endpoints in
      massive weight loss patients undergoing body-contouring procedures. METHODS: A
      retrospective review was conducted over a 6-year period. Patients excluded had
      previous body-contouring procedures or previously treated urinary incontinence.
      Participants completed validated surveys to catalogue preoperative and
      postoperative urinary habits. Patients were then subdivided based on presence of
      preoperative incontinence. Outcomes were compared within and between cohorts
      using the t test and chi-square test. RESULTS: A total of 102 patients completed
      the survey. Of those, 44 had preoperative urinary incontinence. Patients with
      incontinence were found to be significantly older than those who did not.
      Postoperatively, patients with preoperative incontinence had significant
      decreases in incidence and severity of symptoms (p < 0.01, respectively), and
      significantly improved their quality of life (p < 0.02). Over 20 percent noted
      symptom resolution, and 67 percent were mostly or completely satisfied with the
      outcome. CONCLUSIONS: This study is the first to document amelioration of urinary
      incontinence symptoms in massive weight loss patients undergoing body-contouring
      procedures. It adds to the literature suggesting that abdominoplasties in select
      patients may improve incontinence symptoms. Future work will focus on evaluating
      the mechanism of this outcome and documenting improvement in an objective,
      prospective manner. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 28445360
TI  - Facial Danger Zones: Techniques to Maximize Safety during Soft-Tissue Filler
      Injections.
AB  - Given the short recovery and immediate results, facial fillers have become a
      popular alternative to surgical rejuvenation of the face. Reported complications
      arising from facial filler injections include erythema, tissue loss, blindness,
      stroke, and even death. In this article, the authors describe their anatomically
      based techniques to minimize risk and maximize safety when injecting in the
      facial danger zones, including the glabella/brow, temporal region, perioral
      region, nasolabial fold, nose, and infraorbital region. Complications generally
      arise secondary to vasculature injury and/or cannulation with filler. The authors
      have outlined their preferred injection techniques in the facial danger zones
      with respect to the pertinent anatomy in an attempt to minimize risk and maximize
      results. Most importantly, the practitioner should be able to recognize
      complications and address them immediately.

PMID- 28445361
TI  - Adolescent Desire for Cosmetic Surgery: Associations with Bullying and
      Psychological Functioning.
AB  - BACKGROUND: Adolescent bullying may be a key driver of interest in cosmetic
      surgery. This study examined the extent of such interest and whether any effect
      was sex-specific, and examined psychological functioning as a potential mechanism
      through which bullying involvement may lead to a wish for cosmetic surgery.
      METHODS: A two-stage design was used. In the first stage, 2782 adolescents (aged
      11 to 16 years) were screened for bullying involvement using self-reports and
      peer nominations. In the second stage, 752 adolescents who were bullies, victims,
      bully-victims, or uninvolved in bullying reported their desire for cosmetic
      surgery. Psychological functioning was constructed as a composite of self-esteem
      and emotional problems (assessed at stage 1) and body-esteem scores (assessed at
      stage 2). RESULTS: Adolescents involved in bullying in any role were
      significantly more interested in cosmetic surgery than uninvolved adolescents.
      Desire for cosmetic surgery was greatest in adolescents who were bullied (victims
      and bully-victims) and girls. Desire for cosmetic surgery was highest in girls,
      but sex did not interact with bullying role. Being victimized by peers resulted
      in poor psychological functioning, which increased desire for cosmetic surgery.
      In contrast, desire for cosmetic surgery in bullies was not related to
      psychological functioning, which was in the normal range. CONCLUSIONS: Bullying
      victimization is related to poor psychological functioning, and both are related
      to a greater desire for cosmetic surgery in adolescents. Cosmetic surgeons should
      screen candidates for psychological vulnerability and may want to include a short
      screening questionnaire for a history of peer victimization.

PMID- 28445362
TI  - Effect of Human Fat Graft on Breast Cancer Metastasis in a Murine Model.
AB  - BACKGROUND: Isolated adipose stem cells have been reported to encourage migration
      and early metastasis of breast cancer. Mimicking a surgical situation, the
      authors developed a human breast cancer model to evaluate in vivo whether human
      adipose tissue promotes tumor growth and invasion. METHODS: Human adipose tissue
      was obtained from four patients. The MDA-MB-468 cell line was cultured with a
      lentiviral vector encoding a puromycin resistance gene and mCherry fluorescent
      protein. Virus-infected cells were selected. Animals were injected in the left
      renal capsule and divided into three experimental groups: group A, MDA-MB-468
      cells (n = 4); group B, MDA-MB-468 cells/human adipose tissue (n = 4); and group
      C, Dulbecco's Modified Eagle Medium/F-12 medium (negative control, n = 4).
      Metastatic development was monitored using an in vivo imaging system. Small
      breast epithelial mucin (SBEM), human hypoxanthine-guanine
      phosphoribosyltransferase (HPRTh), and murine hypoxanthine-guanine
      phosphoribosyltransferase (HPRTm) expression were analyzed by real-time
      polymerase chain reaction to detect multifocal metastases in right/left renal
      capsule, liver, spleen, and pancreas. RESULTS: Metastasis was observed between
      postinjection days 37 and 44. No significant differences were found in survival
      rates between groups (group A, 157 +/- 42.60 days; group B, 169 +/- 40.17 days).
      All samples expressed HPRTm. HPRTh and SBEM were expressed in left renal capsules
      from all group A and B mice, whereas in spleen, liver, pancreas, and right renal
      capsule the HPRTm and SBEM expression was not constant in all samples of group A
      and B mice. Differences were found between groups in HPRTh and SBEM expression
      but were not statistically significant. CONCLUSION: Human adipose tissue used to
      restore breast defects after oncologic resection did not increase metastasis
      development risk when there were residual breast cancer cells in proximity.

PMID- 28445363
TI  - Indomethacin Enhances Fat Graft Retention by Up-Regulating Adipogenic Genes and
      Reducing Inflammation.
AB  - BACKGROUND: Cell-assisted lipotransfer has been promisingly applied to restore
      soft-tissue defects in plastic surgery; however, the harvesting of stromal
      vascular fraction increases morbidity and poses potential safety hazards. The
      authors investigated whether adding indomethacin, an antiinflammatory
      proadipogenic drug, to the fat graft at the time of transplantation would enhance
      the final graft volume compared with cell-assisted lipotransfer. METHODS: In
      vitro, human adipose-derived stem cells were cultured in conditioned growth media
      supplemented with various doses of indomethacin to investigate adipogenesis and
      the expression of the adipogenic genes. In vivo, lipoaspirate mixed with stromal
      vascular fractions or indomethacin was injected into the dorsum of mice. Tissues
      were harvested at weeks 2, 4, and 12 to evaluate histologic changes. RESULTS: In
      vitro, polymerase chain reaction analysis revealed that increased up-regulation
      of adipogenic genes and activation of the peroxisome proliferator-activated
      receptor-gamma pathway. In vivo, the percentage volume of adipocytes in the
      indomethacin-assisted groups was higher than that in the lipoaspirate-alone
      (control) group at 12 weeks (p = 0.016), and was equivalent to the volume in the
      cell-assisted groups (p = 1.000). Indomethacin improved adipose volumes but had
      no effect on vascularity. A larger number of small adipocytes appeared in the
      treatment samples than in the controls at 2 weeks (p = 0.044) and 4 weeks (p =
      0.021). CONCLUSIONS: Pretreating lipoaspirate with indomethacin enhances the
      final volume retention of engrafted fat. This result is explained in part by
      increased adipogenesis and possibly by the inhibition of inflammatory responses.

PMID- 28445364
TI  - N-Acetylcysteine Prevents Retrograde Motor Neuron Death after Neonatal Peripheral
      Nerve Injury.
AB  - BACKGROUND: Neuronal death may be an overlooked and unaddressed component of
      disability following neonatal nerve injuries, such as obstetric brachial plexus
      injury. N-acetylcysteine and acetyl-L-carnitine improve survival of neurons after
      adult nerve injury, but it is unknown whether they improve survival after
      neonatal injury, when neurons are most susceptible to retrograde neuronal death.
      The authors' objective was to examine whether N-acetylcysteine or acetyl-L
      carnitine treatment improves survival of neonatal motor or sensory neurons in a
      rat model of neonatal nerve injury. METHODS: Rat pups received either a sciatic
      nerve crush or transection injury at postnatal day 3 and were then randomized to
      receive either intraperitoneal vehicle (5% dextrose), N-acetylcysteine (750
      mg/kg), or acetyl-L-carnitine (300 mg/kg) once or twice daily. Four weeks after
      injury, surviving neurons were retrograde-labeled with 4% Fluoro-Gold. The lumbar
      spinal cord and L4/L5 dorsal root ganglia were then harvested and sectioned to
      count surviving motor and sensory neurons. RESULTS: Transection and crush
      injuries resulted in significant motor and sensory neuron loss, with transection
      injury resulting in significantly less neuron survival. High-dose N
      acetylcysteine (750 mg/kg twice daily) significantly increased motor neuron
      survival after neonatal sciatic nerve crush and transection injury. Neither N
      acetylcysteine nor acetyl-L-carnitine treatment improved sensory neuron survival.
      CONCLUSIONS: Proximal neonatal nerve injuries, such as obstetric brachial plexus
      injury, produce significant retrograde neuronal death after injury. High-dose N
      acetylcysteine significantly increases motor neuron survival, which may improve
      functional outcomes after obstetrical brachial plexus injury.

PMID- 28445365
TI  - Improvement of Flap Necrosis in a Rat Random Skin Flap Model by In Vivo
      Electroporation-Mediated HGF Gene Transfer.
AB  - BACKGROUND: Despite great understanding of underlying mechanisms for flap
      necrosis and advances in surgical techniques, flap necrosis remains a critical
      issue. In the present study, the authors investigated the efficacy of
      electroporation-mediated hepatocyte growth factor (HGF) gene delivery to random
      dorsal skin flaps (McFarlane) to accelerate wound healing and reduce flap
      necrosis. METHODS: Fifteen male Wistar rats (290 to 320 g) were divided randomly
      into three groups. Group a, the control group (n = 5), underwent surgery and
      received no gene transfer. Group b received electroporation-mediated HGF gene
      delivery 24 hours after surgery as a treatment. Group c received electroporation
      mediated HGF gene delivery 24 hours before surgery as prophylaxis (n = 5).
      Planimetry, laser Doppler imaging, and immunohistochemistry were used to assess
      the efficacy of HGF gene therapy among the groups. RESULTS: Electroporation
      mediated HGF gene delivery significantly decreased flap necrosis percentage
      compared with the control group in prophylactic and treatment groups (p = 0.0317
      and p = 0.0079, respectively) and significantly increased cutaneous perfusion
      compared with the control group (p = 0.0317 and p = 0.0159, respectively).
      Moreover, Spearman rank correlation showed a significant negative correlation
      between flap necrosis percentage and laser index (p = 0.0213 and r = -0.5964,
      respectively). Furthermore, significantly higher mean CD31 vessel density was
      detected in treatment and prophylactic groups (p = 0.0079 and p = 0.0159,
      respectively). In addition, quantitative image analysis revealed significantly
      higher HGF protein expression in groups b and c (p = 0.0079 and p = 0.0079,
      respectively). CONCLUSION: These findings suggested in vivo electroporation
      mediated HGF gene delivery enhanced viability and vascularity of the ischemic
      skin flap.

PMID- 28445366
TI  - Biomechanical Integrity in Craniofacial Surgery: Calvarial Reconstruction in
      Favorable and Infected Defects with Bone Morphogenetic Protein 2.
AB  - BACKGROUND: The limitations of autologous and alloplastic reconstruction for
      craniofacial bone defects have created a clinical need for viable tissue
      engineering strategies. Recombinant human bone morphogenetic protein-2 (rhBMP-2)
      has shown promise in this setting. The aim of this study was to determine the
      long-term biomechanical properties of rhBMP-2-mediated calvarial reconstruction.
      METHODS: Twelve-week-old New Zealand White rabbits underwent subtotal
      calvarectomy. Defects were repaired in one of several groups: immediate
      reconstruction with autologous graft, immediate reconstruction with cryopreserved
      bone graft, immediate reconstruction with rhBMP-2 (favorable), and delayed
      reconstruction with rhBMP-2 following infection and subsequent debridement
      (unfavorable). Cryopreserved reconstructions were measured at 6 weeks; autologous
      reconstructions were measured at 6 weeks and 6 months; and both favorable and
      unfavorable rhBMP-2 reconstructions were assessed at 6 weeks, 6 months, and 1
      year after reconstruction. Healing was assessed with computed tomography. An
      unconfined compression test was performed for biomechanical analysis. Stress at
      20 percent strain, percentage relaxation, tangent modulus, and final strain at
      1800 N were compared between groups. RESULTS: Nearly complete radiographic
      coverage was achieved by 6 months for autologous reconstruction and by 6 weeks
      for rhBMP-2 reconstruction. Favorable rhBMP-2 reconstruction demonstrated a
      larger final strain at 1800 N through 1 year compared with native bone. Bone in
      unfavorable rhBMP-2 reconstruction was more compressible than native bone, with a
      larger final strain at 1800 N at 1 year. There were no significant differences
      between favorable and unfavorable groups. CONCLUSIONS: Despite providing
      radiographic coverage, the biomechanical properties of rhBMP-2 bone differ from
      those of native bone. Further studies are warranted to determine how these
      properties affect overall strength and structural integrity.

PMID- 28445367
TI  - Adipose Tissue Drives Response to Ischemia-Reperfusion Injury in a Murine
      Pressure Sore Model.
AB  - BACKGROUND: Ischemia-reperfusion injury contributes significantly to the
      pathogenesis of chronic wounds such as pressure sores and diabetic foot ulcers.
      The authors' laboratory has previously developed a cyclical murine ischemia
      reperfusion injury model. The authors here use this model to determine factors
      underlying tissue response to ischemia-reperfusion injury. METHODS: C57BL/6 mice
      were subjected to cycles of ischemia-reperfusion that varied in number (one to
      four cycles) and duration of ischemia (1 to 2 hours). For each ischemia
      reperfusion condition, the following variables were analyzed: (1) digital
      photographs for area of necrosis; (2) hematoxylin and eosin staining and
      immunohistochemistry for inflammatory infiltrate; and (3) expression of
      inflammatory markers by quantitative polymerase chain reaction. In addition,
      human adipocytes and fibroblasts were cultured in vitro under conditions of
      hypoxia and reoxygenation, and expression of inflammatory markers was analyzed by
      quantitative polymerase chain reaction. RESULTS: Increases in both ischemia
      reperfusion cycle number and ischemia duration correlated with increased areas of
      epithelial necrosis both grossly and histologically, and with an increase in
      cellularity and neutrophil density. This increased inflammatory infiltrate and a
      significant increase in the expression of proinflammatory markers (Hmox1,
      interleukin-6, interleukin-1, and monocyte chemoattractant protein-1) was
      observed in adipose tissue subjected to ischemia-reperfusion injury, but not in
      dermis. These results were mirrored in human adipose tissue. CONCLUSIONS: The
      authors further characterize a novel, reproducible murine model of ischemia
      reperfusion injury. The results of their study indicate that adipose tissue is
      less tolerant of ischemia-reperfusion than dermal tissue. Rather than being an
      "innocent bystander," adipose tissue plays an active role in driving the
      inflammatory response to ischemia-reperfusion injury.

PMID- 28445368
TI  - Correcting Concavity of Rabbit Auricular Cartilage: Comparison of Single Scoring
      Incisions with Butyl Cyanoacrylate-Aided Techniques.
AB  - BACKGROUND: The authors present the results of an experimental study in which
      four different techniques were used for the correction of concave rabbit
      auricular cartilage. METHODS: Sixteen New Zealand adult male rabbits were used in
      the study. Butyl cyanoacrylate-aided cartilage graft fixation and butyl
      cyanoacrylate-aided bone graft fixation and scoring technique, alone or combined
      with butyl cyanoacrylate application, were performed to correct the concavity of
      rabbit auricular cartilage. RESULTS: Angle measurements showed that all four
      techniques were efficient for correction of the cartilage concavities. However,
      the mean postsacrifice angles of the graft fixation groups were significantly
      higher than those of the other study groups, reflecting the fact that graft
      fixation with butyl cyanoacrylate application was more efficient for preserving
      the final cartilage shape. Furthermore, in the ninth month, graft fixation groups
      had the lowest chondrocyte densities, the highest degree of inflammation, the
      highest degree of foreign body reaction, and the highest butyl cyanoacrylate
      density. CONCLUSIONS: Fibrosis or chondrocyte proliferation on scoring incision
      lines is not an associated feature of this technique. When the incision depths
      were standardized, the scoring technique provided efficacy similar to that of the
      scoring incisions combined with butyl cyanoacrylate application for correction of
      the cartilage concavity. The scoring incision plus butyl cyanoacrylate group
      showed less toxicity than the graft fixation groups because of rapid removal of
      toxic breakdown products. Graft fixation techniques were superior to other
      corrective procedures with regard to preservation of the final cartilage shape.
      Although they resulted in greater toxicity, the cartilage correction was not
      affected unfavorably.

PMID- 28445369
TI  - A Systematic Review of Different Implants and Approaches for Proximal
      Interphalangeal Joint Arthroplasty.
AB  - BACKGROUND: Outcomes after implant arthroplasty for primary degenerative and
      posttraumatic osteoarthritis of the proximal interphalangeal joint were different
      according to the implant design and surgical approach. The purpose of this
      systematic review was to evaluate outcomes of various types of implant
      arthroplasty for proximal interphalangeal joint osteoarthritis, with an emphasis
      on different surgical approaches. METHODS: The authors searched all available
      literature in the PubMed and EMBASE databases for articles reporting on outcomes
      of implant arthroplasty for proximal interphalangeal joint osteoarthritis. Data
      collection included active arc of motion, extension lag, and complications. The
      authors combined the data of various types of surface replacement arthroplasty
      into one group for comparison with silicone arthroplasty. RESULTS: A total of 849
      articles were screened, yielding 40 studies for final review. The mean
      postoperative arc of motion and the mean gain in arc of motion of silicone
      implant with the volar approach were 58 and 17 degrees, respectively, which was
      greater than surface replacement implant with the dorsal approach at 51 and 8
      degrees, respectively. The mean postoperative extension lag of silicone implant
      with the volar approach and surface replacement with the dorsal approach was 5
      and 14 degrees, respectively. The revision rate of silicone implant with the
      volar approach and surface replacement with the dorsal approach was 6 percent and
      18 percent at a mean follow-up of 41.2 and 51 months, respectively. CONCLUSION:
      Silicone implant with the volar approach showed the best arc of motion, with less
      extension lag and fewer complications after surgery among all the implant designs
      and surgical approaches.

PMID- 28445370
TI  - Discussion: Primary Septal Cartilage Graft for the Unilateral Cleft Rhinoplasty.

PMID- 28445371
TI  - Preventing Early-Stage Graft Bone Resorption by Simultaneous Innervation:
      Innervated Iliac Bone Flap for Mandibular Reconstruction.
AB  - BACKGROUND: Postoperative resorption of vascularized bone grafts jeopardizes the
      success of dental implant(s) and functional rehabilitation of the jaw. Recent
      evidence supports the crucial role of innervation in bone regeneration and
      turnover. METHODS: This study reports a new technique for simultaneous
      innervation of vascularized iliac flaps in mandibular reconstruction, through
      neurorrhaphy between ilioinguinal nerves, which innervate iliac bone, and
      inferior alveolar nerves or great auricular nerves. Twenty-two patients (aged 50
      to 69 years) with postoncologic continuity defects of the mandible underwent
      mandibular reconstruction (10 innervated flaps and 12 control flaps). Graft bone
      resorption was analyzed by computed tomographic scans at 6 and 12 months
      postoperatively, and bone quality was evaluated for dental implantation, with
      histologic and histomorphometric analyses for graft samples. RESULTS: At 12-month
      follow-up, graft bone density loss in the control group was significantly higher
      than in the innervated group (p < 0.05). Bone quality evaluation indicated a
      suitable condition for dental implantation in all patients in the innervated
      group but in 41.7 percent of patients in the control group. Histologic and
      histomorphometric analyses showed successful innervation in the innervated group
      but not in the control group. Osteoclast activity was significantly higher in the
      control group than in the innervated group (p < 0.05). CONCLUSIONS: Innervated
      iliac flaps may effectively prevent bone resorption of grafts in mandible
      reconstruction that otherwise jeopardize the success of dental implants. This new
      strategy of innervation of bone flaps appears clinically valuable and provides
      insights into the homeostasis of grafts for functional reconstruction. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 28445372
TI  - Longitudinal Photogrammetric Analysis of the Columellar-Labial Angle following
      Primary Repair of Bilateral Cleft Lip and Nasal Deformity.
AB  - BACKGROUND: The changing nasolabial dimensions after repair of bilateral cleft
      lip and nasal deformity can be documented by anthropometry; however, the
      columellar-labial angle is rarely measured. METHODS: This is a study of white
      patients who had synchronous repair of bilateral cleft lip performed by one
      surgeon (J.B.M.). The columellar-labial angle was measured on lateral photographs
      with the subject in neutral head position. Average values for columellar-labial
      angle at two or more time points were analyzed with a general estimating equation
      and cubic modeling. Values for complete and incomplete bilateral cleft lips were
      compared to each other and to Farkas' norms. Direct anthropometric measurements
      of intraoperative columellar length were compared to the postoperative columellar
      labial angle using Pearson correlation analysis. RESULTS: Eighty-five patients
      were studied (64 complete and 21 incomplete clefts). The average photographic
      follow-up interval was 10 years (range, 1.8 to 19.5 years). The columellar-labial
      angle in bilateral complete clefts was significantly greater than in incomplete
      forms (p = 0.002). Although the angles decreased with time, they remained
      significantly greater than Farkas' normative values in both cleft groups (all p <
      0.05). There was no correlation between the magnitude of columellar lengthening
      achieved during primary nasal correction and the postoperative columellar-labial
      angle. CONCLUSIONS: An obtuse columellar-labial angle can occur following
      synchronous nasolabial repair of a bilateral cleft lip, particularly in patients
      with a complete deformity. Although the angle narrows in time, it remains 1 to 2
      SD greater than normal values. Secondary nasal correction may be needed if there
      is excessive tip rotation after completion of growth and orthognathic surgery.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 28445373
TI  - Auricular Reconstruction in Hemifacial Microsomia with an Expanded Two-Flap
      Method.
AB  - BACKGROUND: Reconstruction of external ear is important for the child/adult with
      craniofacial deformities to achieve balance and harmony of the face and head. The
      aim of this study was to investigate the clinical application of an expanded two
      flap method for auricular reconstruction in hemifacial microsomia. METHODS:
      Between January of 2014 and November of 2015, 111 hemifacial microsomia patients
      with microtia underwent auricular reconstruction with an expanded two-flap
      method. The clinical data of these patients were reviewed retrospectively. Thirty
      two patients (28.8 percent) underwent auricular reconstruction in combination
      with simultaneous mandibular lengthening. Microtia was treated by an expanded two
      flap method, which includes three stages. In the first stage, the retroauricular
      skin was expanded using a kidney-shaped tissue expander. In the second stage, the
      costal cartilage was harvested and the framework was fabricated. The anterior
      surface of the framework was enveloped by the expanded skin flap. The posterior
      surface and the helical rim of the framework is covered by a retroauricular
      fascial flap and a full-thickness skin graft. In the third stage, the tragus was
      reconstructed, the lobule was formed, and the concha was excavated. The surgical
      planning and skills of auricular reconstruction-especially for hemifacial
      microsomia-were described and analyzed. The median duration of follow-up was 8.3
      months. RESULTS: There were nine cases (8.1 percent) of complications in our
      study. During follow-up, 103 patients (92.8 percent) had satisfactory outcomes,
      seven (6.3 percent) had partially satisfactory outcomes, and one patient (0.9
      percent) had an unsatisfactory outcome. CONCLUSION: Auricular reconstruction
      using an expanded two-flap method in hemifacial microsomia is safe and effective,
      with satisfying middle-term results. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 28445374
TI  - Treatment of Isolated Zygomatic Arch Fracture: Improved Outcomes with External
      Splinting.
AB  - BACKGROUND: The various approaches to reduction and fixation of isolated
      displaced zygomatic arch fractures have not been well studied. The authors
      compared established treatment methods for zygomatic arch fractures for both
      aesthetic and functional outcomes. METHODS: Consecutive patients with isolated
      zygomatic arch fractures with a minimum of 6 months' follow-up were studied in
      five groups: group 1, intraoral approach (no fixation); group 2, temporal
      approach (no fixation); group 3, coronal flap plate fixation; group 4, external
      splint fixation; and group 5, no surgery. Perioperative complications, facial
      contour symmetry (aesthetic outcome), improvement in mouth opening (functional
      outcome), and reoperations were compared. RESULTS: Patients undergoing external
      splint fixation had no perioperative complications. Coronal flap plate fixation
      had the highest rate of perioperative complications (46 percent), with facial
      nerve injury (4 percent), hematoma (8 percent), and persistent hyperesthesia (8
      percent). Reoperations (fat grafting or bony reconstruction) were highest with
      coronal flap plate fixation (23 percent) and the temporal approach (7.7 percent);
      external splint fixation and the intraoral approach required no reinterventions.
      Patients treated with external splint fixation had the largest improvement in
      mean interincisor mouth opening. Mean postoperative interincisor opening in
      decreasing order was as follows: external splint fixation (51.6 mm), coronal flap
      plate fixation (47.1 mm), no surgery (39.8 mm), intraoral approach (39.6 mm), and
      temporal approach (38.9 mm). The highest volumetric symmetry was seen in external
      splint fixation (97.9 percent), followed by coronal flap plate fixation (94
      percent), temporal approach (76.2 percent), intraoral approach (73 percent), and
      no surgery (68.3 percent). CONCLUSION: For isolated zygomatic arch fracture,
      patients undergoing external splint fixation had the lowest risk of perioperative
      complications and the greatest improvement in functional and aesthetic outcomes
      compared with the intraoral approach (no fixation), the temporal approach (no
      fixation), coronal flap plate fixation, and no surgery. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, II.

PMID- 28445375
TI  - A New Classification of Three-Dimensional Printing Technologies: Systematic
      Review of Three-Dimensional Printing for Patient-Specific Craniomaxillofacial
      Surgery.
AB  - BACKGROUND: Three-dimensional printing technology has been advancing in surgical
      applications. This systematic review examines its patient-specific applications
      in craniomaxillofacial surgery. METHODS: Terms related to "three-dimensional
      printing" and "surgery" were searched on PubMed on May 4, 2015; 313 unique
      articles were returned. Inclusion and exclusion criteria concentrated on patient
      specific surgical applications, yielding 141 full-text articles, of which 33
      craniomaxillofacial articles were analyzed. RESULTS: Thirty-three articles
      included 315 patients who underwent three-dimensional printing-assisted
      operations. The most common modeling software was Mimics, the most common
      printing software was 3D Systems, the average time to create a printed object was
      18.9 hours (range, 1.5 to 96 hours), and the average cost of a printed object was
      $1353.31 (range, $69.75 to $5500). Surgical procedures were divided among 203
      craniofacial patients (205 three-dimensional printing objects) and 112
      maxillofacial patients (137 objects). Printing technologies could be classified
      as contour models, guides, splints, and implants. For craniofacial patients, 173
      contour models (84 percent), 13 guides (6 percent), two splints (1 percent), and
      17 implants (8 percent) were made. For maxillofacial patients, 41 contour models
      (30 percent), 48 guides (35 percent), 40 splints (29 percent), and eight implants
      (6 percent) were made. These distributions were significantly different (p <
      0.0001). Four studies compared three-dimensional printing techniques to
      conventional techniques; two of them found that three-dimensional printing
      produced improved outcomes. CONCLUSIONS: Three-dimensional printing technology in
      craniomaxillofacial surgery can be classified into contour models (type I),
      guides (type II), splints (type III), and implants (type IV). These four methods
      vary in their use between craniofacial and maxillofacial surgery, reflecting
      their different goals. This understanding may help advance and predict three
      dimensional printing applications for other types of plastic surgery and beyond.

PMID- 28445376
TI  - Defining Temporal Hairline Landmarks.
AB  - Brow dermoids are benign pediatric neoplasms. Endoscopic resection requires
      incisions placed within the temporal hairline, which is often difficult to
      reliably locate in infants. The authors studied adult and pediatric patients to
      define the location of the hairline in relationship to simple facial landmarks.
      Adult and pediatric patients who were seen in preoperative consultation for
      facial surgical procedures were identified and included in the study. Patients
      with a history of facial trauma, surgery, or congenital anomalies were excluded.
      Digital photographs were analyzed to measure corneal white-to-white diameter.
      Lines were drawn connecting the tragus to the lateral canthus and from the
      inferiormost aspect of the earlobe bisecting the first line (line A). The maximal
      distance between line A and the temporal hairline was recorded. One hundred
      sixteen patients met the inclusion criteria, 81 adults and 35 pediatric patients.
      Average age was 55.9 years in adults and 3.2 years in the pediatric group.
      Measurements were normalized to the corneal diameter. Average temporal hairline
      distance from line A was 25.0 mm in adults and 21.8 mm in the pediatric group.
      Hairline position was not correlated with age or sex. The temporal hairline can
      be reliably located relative to a line drawn from the inferior aspect of the
      earlobe to the midpoint of the line connecting the lateral canthus and tragus.
      The temporal hairline is within 30 mm of this line. When designing a temporal
      hairline incision in infants, it can be safely placed 30 mm or more posterior to
      this line to ensure a well-hidden scar.

PMID- 28445377
TI  - First Lower Two-Thirds Osteomyocutaneous Facial Allograft Perfused by a
      Unilateral Facial Artery: Outcomes and Vascularization at 1 Year after
      Transplantation.
AB  - BACKGROUND: Facial allotransplantation provides a unique opportunity to restore
      facial form and function in severely disfigured patients. Using a single
      unilateral facial artery for vascularization can significantly reduce surgical
      duration and thus facilitate the practice of face transplantation. METHODS: A 33
      year-old man with a history of high-energy ballistic trauma received a facial
      allograft comprising the lower two-thirds of the face, including maxilla and
      mandible. Vascular anastomoses involved one unilateral facial artery and two
      veins. Vascularization patterns, airway volume, and facial functions were
      assessed before and 1 year after transplantation. In addition, immunosuppressive
      therapy and rejection episodes were recorded. RESULTS: One year after
      transplantation, the facial allograft is well perfused and gradually improving in
      function. Unilateral facial artery anastomosis remains patent and
      collateralization with the contralateral side is taking place through collaterals
      of the submental arteries. Bony perfusion of the maxilla and mandible is provided
      periosteally. Bilateral venous outflow is evident. Airway volume is significantly
      increased compared with before transplantation, and gastrostomy and tracheostomy
      tubes have been securely removed. The recipient has gained the abilities to
      smell, speak, feel, and grimace 1 year after transplantation. Steroids were
      successfully weaned after 9 months, leaving the patient on dual immunosuppressive
      therapy with tacrolimus and mycophenolate mofetil. Two rejection episodes
      occurred, of which one was treated by steroid pulse and the other by adjusting
      the maintenance therapy. CONCLUSIONS: In this patient, a facial allograft
      comprising the lower two-thirds of the face including the maxilla and mandible is
      sufficiently perfused by one unilateral facial artery. Bilateral venous outflow,
      however, seems to be necessary. Facial allotransplantation can significantly and
      securely improve facial form and function. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, V.

PMID- 28445378
TI  - The Impact of Body Mass Index on Abdominal Wall Reconstruction Outcomes: A
      Comparative Study.
AB  - BACKGROUND: Obesity and higher body mass index may be associated with higher
      rates of wound healing complications and hernia recurrence rates following
      complex abdominal wall reconstruction. The authors hypothesized that higher body
      mass indexes result in higher rates of postoperative wound healing complications
      but similar rates of hernia recurrence in abdominal wall reconstruction patients.
      METHODS: The authors included 511 consecutive patients who underwent abdominal
      wall reconstruction with underlay mesh. Patients were divided into three groups
      on the basis of preoperative body mass index: less than 30 kg/m (nonobese), 30 to
      34.9 kg/m (class I obesity), and 35 kg/m or greater (class II/III obesity). The
      authors compared postoperative outcomes among these groups. RESULTS: Class I and
      class II/III obesity patients had higher surgical-site occurrence rates than
      nonobese patients (26.4 percent versus 14.9 percent, p = 0.006; and 36.8 percent
      versus 14.9 percent, p < 0.001, respectively) and higher overall complication
      rates (37.9 percent versus 24.7 percent, p = 0.007; and 43.4 percent versus 24.7
      percent, p < 0.001, respectively). Similarly, obese patients had significantly
      higher skin dehiscence (19.3 percent versus 7.2 percent, p < 0.001; and 26.5
      percent versus 7.2 percent, p < 0.001, respectively) and fat necrosis rates (10.0
      percent versus 2.1 percent, p = 0.001; and 11.8 percent versus 2.1 percent, p <
      0.001, respectively) than nonobese patients. Obesity class II/III patients had
      higher infection and seroma rates than nonobese patients (9.6 percent versus 4.3
      percent, p = 0.041; and 8.1 percent versus 2.1 percent, p = 0.006, respectively).
      However, class I and class II/III obesity patients experienced hernia recurrence
      rates (11.4 percent versus 7.7 percent, p = 0.204; and 10.3 percent versus 7.7
      percent, p = 0.381, respectively) and freedom from hernia recurrence (overall log
      rank, p = 0.41) similar to those of nonobese patients. CONCLUSION: Hernia
      recurrence rates do not appear to be affected by obesity on long-term follow-up
      in abdominal wall reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 28445379
TI  - Discussion: The Impact of Body Mass Index on Abdominal Wall Reconstruction
      Outcomes: A Comparative Study.

PMID- 28445381
TI  - Regulatory Advocacy Update: American Society of Plastic Surgeons Comments in
      Response to the U.S. Food and Drug Administration Draft Guidance Documents on
      Human Cell and Tissue Products.
AB  - The U.S. Food and Drug Administration released draft guidance documents on human
      cells, tissues, and cellular and tissue-based products regulations. These
      proposed guidance documents can impact the practice of plastic surgery in the
      area of tissue grafting procedures. This article describes the relevant issues in
      these draft guidance documents, and presents the comments provided to the U.S.
      Food and Drug Administration by the American Society of Plastic Surgeons.

PMID- 28445380
TI  - A Formidable Foe Is Sabotaging Your Results: What You Should Know about Biofilms
      and Wound Healing.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Describe biofilm pathogenesis as it relates to problem wounds. 2.
      Understand the preclinical and clinical evidence implicating biofilm in problem
      wounds. 3. Explain the diagnostic and treatment challenges that biofilms create
      for problem wounds. 4. Demonstrate a basic understanding of emerging strategies
      aimed at counteracting these processes. SUMMARY: Biofilm represents a protected
      mode of growth for bacteria, allowing them to evade standard diagnostic
      techniques and avoid eradication by standard therapies. Although only recently
      discovered, biofilm has existed for millennia and complicates nearly every aspect
      of medicine. Biofilm impacts wound healing by allowing bacteria to evade immune
      responses, prolonging inflammation and disabling skin barrier function. It is
      important to understand why problem wounds persist despite state-of-the-art
      treatment, why they are difficult to accurately diagnose, and why they recur. The
      aim of this article is to focus on current gaps in knowledge related to problem
      wounds, specifically, biofilm infection.

PMID- 28445382
TI  - Evidence-Based Medicine in Aesthetic Surgery: The Significance of Level to
      Aesthetic Surgery.
AB  - Since its popularization in the 1980s, evidence-based medicine has become the
      cornerstone of American health care. Many specialties rapidly adapted to the
      paradigm shift of health care by delivering treatment using the evidence-based
      guidelines. However, the field of plastic surgery has been slow to implement
      evidence-based medicine compared with the other specialties because of the
      challenges of performing randomized controlled trials, such as funding,
      variability in surgical skills, and difficulty with standardization of
      techniques. To date, aesthetic surgery has been at the forefront of evidence
      based medicine in plastic surgery by having the most randomized controlled
      trials. Nevertheless, a detailed analysis of these studies has not been
      previously performed. In this article, the level I and II articles of aesthetic
      surgery are discussed to increase awareness of high-quality evidence-based
      medicine in aesthetic surgery.

PMID- 28445383
TI  - Discussion: Business Education for Plastic Surgeons: A Systematic Review,
      Development, and Implementation of a Business Principles Curriculum in a
      Residency Program.

PMID- 28445384
TI  - #Giving Back: Why It Matters!

PMID- 28445385
TI  - Reply: Antibiotic Prophylaxis following Implant-Based Breast Reconstruction: What
      Is the Evidence?

PMID- 28445386
TI  - Reply: Nostrilplasty by Manipulating the Dilator Naris Muscles: A Pilot Study.

PMID- 28445387
TI  - Reply: The Concepts of Propeller, Perforator, Keystone, and Other Local Flaps and
      Their Role in the Evolution of Reconstruction.

PMID- 28445388
TI  - Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol
      A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and
      Nutrient Transporters Gene Expression in Newborn and Weaning Pigs.
AB  - This study was conducted to explore whether exposure to bisphenol A (BPA) during
      pregnancy could change intestinal digestion and absorption function in offspring
      using pigs as a model, and whether methyl donor (MET) could counteract the BPA
      induced impacts. Fifty Landrace * Yorkshire sows were divided into four dietary
      groups throughout gestation: control diet (CON); control diet supplemented with
      BPA (50 mg/kg); control diet supplemented with MET (3 g/kg betaine, 400 mg/kg
      choline, 150 MUg/kg vitamin B12, and 15 mg/kg folic acid); and control diet with
      BPA and MET supplementation (BPA + MET). Intestine samples were collected from
      pigs' offspring at birth and weaning. Maternal BPA exposure during pregnancy
      significantly reduced the ratio of jejunum villus height to crypt depth,
      decreased the jejunum sucrase activity, down-regulated the mRNA expression of
      jejunum peptide transporter 1 (Pept1) and DNA methyl transferase 3a (DNMT3a), and
      decreased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05).
      Maternal MET supplementation significantly raised the ratio of villus height to
      crypt depth in jejunum and ileum, improved the jejunum lactase activity, up
      regulated the mRNA expression of jejunum Pept1, lactase (LCT), DNMT1, DNMT3a, and
      methylenetetrahydrofolate reductase (MTHFR), and increased the DNA methylation
      level of jejunum Pept1 in offspring (p < 0.05). However, the ratio of jejunum
      villus height to crypt depth was higher in BPA + MET treatment compared with CON
      and BPA treatment (p < 0.05). Meanwhile, there was no difference in the jejunum
      sucrase activity, the mRNA expression of jejunum Pept1 and DNMT3a, and the DNA
      methylation level of jejunum Pept1 between CON and BPA + MET treatment. These
      results indicated that maternal exposure to BPA during gestation might suppress
      offspring's intestinal digestion and absorption function, whereas supplementation
      of MET could counteract these damages, which might be associated with DNA
      methylation.

PMID- 28445391
TI  - Telomerase Inhibitory Effects of Red Pigment Rubropunctatin and Statin Monacolin
      L Isolated from Red Yeast Rice.
AB  - In addition to the cholesterol-lowering activity of red yeast rice (RYR), its
      anticancer activities have been frequently reported. However, the mechanism of
      action of the anticancer activity of RYR is not yet fully understood. The
      objective of the current study was to elucidate anticancer compositions and
      anticancer mechanism of actions of RYR. The isolated compounds from RYR were
      subjected to anti-proliferation assay, apoptosis assay via flow cytometry, and
      telomerase inhibitory assay via telomeric repeat amplification protocol-PCR (TRAP
      PCR) assay, and Western blotting assay in an in vitro cell culture system. The
      results showed that a statin, monacolin L, and a red pigment, rubropunctatin,
      from RYR exhibited very strong cancer cell proliferation inhibitory effects; the
      rubropunctatin was comparable with anticancer drug cis-platinum, taxol, and 10
      hydroxy-camptothecin (HCPT) in their IC50 values. Monacolin L and rubropunctatin
      exerted their anticancer activity via telomerase inhibitory effects. Monacolin L
      and rubropunctatin presented the similar telomerase inhibitory effects as the
      anticancer drug cis-platinum, while the anticancer drug HCPT presented a weak
      telomerase inhibitory effect in the TRAP-PCR assay. Meanwhile, rubropunctatin and
      cis-platinum did not present strong apoptosis induction activity as the momacolin
      L and HCPT did. These results indicate that the RYR may exert anticancer effects
      through the telomerase inhibitory effect of rubropunctatin and the apoptosis
      induction effect of monacolin L.

PMID- 28445392
TI  - Death Cafes: Death Doulas and Family Communication.
AB  - The Death Cafe is part of the Death Positive movement, and as such, is uniquely
      positioned to bring the dialogue about death and dying to the public.
      Participants in a Death Cafe typically have two different perspectives. Some
      participants have not experienced death in their family and friends' circle and
      wish to converse with others about their beliefs on death and dying. Others are
      those who have experienced death somewhere in their circle of friends and
      families. One of goals of the Death Cafe facilitators is to help attendees
      reconcile their family narratives regarding death using the broader lens of the
      Death Cafe. Using the insights provided by interviews from 15 Death Cafe
      facilitators, this manuscript discusses the role of the Death Cafe facilitators
      as the death doulas of family communication.

PMID- 28445389
TI  - Fructose, Glucocorticoids and Adipose Tissue: Implications for the Metabolic
      Syndrome.
AB  - The modern Western society lifestyle is characterized by a hyperenergetic, high
      sugar containing food intake. Sugar intake increased dramatically during the last
      few decades, due to the excessive consumption of high-sugar drinks and high
      fructose corn syrup. Current evidence suggests that high fructose intake when
      combined with overeating and adiposity promotes adverse metabolic health effects
      including dyslipidemia, insulin resistance, type II diabetes, and inflammation.
      Similarly, elevated glucocorticoid levels, especially the enhanced generation of
      active glucocorticoids in the adipose tissue due to increased 11beta
      hydroxysteroid dehydrogenase 1 (11beta-HSD1) activity, have been associated with
      metabolic diseases. Moreover, recent evidence suggests that fructose stimulates
      the 11beta-HSD1-mediated glucocorticoid activation by enhancing the availability
      of its cofactor NADPH. In adipocytes, fructose was found to stimulate 11beta-HSD1
      expression and activity, thereby promoting the adipogenic effects of
      glucocorticoids. This article aims to highlight the interconnections between
      overwhelmed fructose metabolism, intracellular glucocorticoid activation in
      adipose tissue, and their metabolic effects on the progression of the metabolic
      syndrome.

PMID- 28445390
TI  - Prevention of Colorectal Cancer by Targeting Obesity-Related Disorders and
      Inflammation.
AB  - Colorectal cancer is a major healthcare concern worldwide. Many experimental and
      clinical studies have been conducted to date to discover agents that help in the
      prevention of this disease. Chronic inflammation in colonic mucosa and obesity,
      and its related metabolic abnormalities, are considered to increase the risk of
      colorectal cancer. Therefore, treatments targeting these factors might be a
      promising strategy to prevent the development of colorectal cancer. Among a
      number of functional foods, various phytochemicals, including tea catechins,
      which have anti-inflammatory and anti-obesity properties, and medicinal agents
      that ameliorate metabolic disorders, might also be beneficial in the prevention
      of colorectal cancer. In this review article, we summarize the strategies for
      preventing colorectal cancer by targeting obesity-related disorders and
      inflammation through nutraceutical and pharmaceutical approaches, and discuss the
      mechanisms of several phytochemicals and medicinal drugs used in basic and
      clinical research, especially focusing on the effects of green tea catechins.

PMID- 28445393
TI  - Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement
      Technique.
AB  - In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted
      that a single molecule could act as a diode, in which electronic current can be
      rectified. The electronic rectification property of the diode is one of basic
      functions of electronic components and since then, the molecular diode has been
      investigated as a first single-molecule device that would have a practical
      application. In this review, we first describe the experimental fabrication and
      electronic characterization techniques of molecular diodes consisting of a small
      number of molecules or a single molecule. Then, two main mechanisms of the
      rectification property of the molecular diode are discussed. Finally,
      representative results for the molecular diode are reviewed and a brief outlook
      on crucial issues that need to be addressed in future research is discussed.

PMID- 28445394
TI  - Spectroscopic Detection of Glyphosate in Water Assisted by Laser-Ablated Silver
      Nanoparticles.
AB  - Glyphosate is one of the most widely used herbicides in the world. Its safety for
      both human health and aquatic biomes is a subject of wide debate. There are
      limits to glyphosate's presence in bodies of water, and it is usually detected
      through complex analytical procedures. In this work, the presence of glyphosate
      is detected directly through optical interrogation of aqueous solution. For this
      purpose, silver nanoparticles were produced by pulsed laser ablation in liquids.
      Limits of detection of 0.9 mg/L and 3.2 mg/L were obtained with UV-Vis extinction
      and Surface Enhanced Raman spectroscopies, respectively. The sensing mechanism
      was evaluated in the presence of potential interferents as well as with
      commercial glyphosate-based herbicides.

PMID- 28445395
TI  - A Modified Lamb Wave Time-Reversal Method for Health Monitoring of Composite
      Structures.
AB  - Because the time reversal operator of Lamb waves varies with frequency in
      composite structures, the reconstructed signal deviates from the input signal
      even in undamaged cases. The damage index captures the discrepancy between the
      two signals without differentiating the effects of time reversal operator from
      those of damage. This results in the risk of false alarm. To solve this issue, a
      modified time reversal method (MTRM) is proposed. In this method, the frequency
      dependence of the time reversal operator is compensated by two steps. First, an
      amplitude modulation is placed on the input signal, which is related to the
      excitability, detectability, and attenuation of the Lamb wave mode. Second, the
      damage index is redefined to measure the deviation between the reconstructed
      signal and the modulated input signal. This could indicate the presence of damage
      with better performance. An experimental investigation is then conducted on a
      carbon fiber-reinforced polymer (CFRP) laminate to illustrate the effectiveness
      of the MTRM for identifying damage. The results show that the MTRM may provide a
      promising tool for health monitoring of composite structures.

PMID- 28445396
TI  - miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric
      Cancer.
AB  - MicroRNAs (miRNAs) play important roles in the cancer development and
      progression; overexpression of miR-103 has been identified in various tumors.
      However, its biological function and regulatory mechanism involved in modulation
      of human gastric cancer (GC) remain largely unknown. This study aimed to confirm
      clinical significance of miR-103 and investigate its biological role and
      underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103
      was highly expressed in GC tissues and cell lines. miR-103 expression was
      correlated closely with tumor size, Lauren's classification, and lymph node
      metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of
      miR-103 was significantly associated with poor overall survival and disease-free
      survival of GC patients. Downregulation of miR-103 by transfecting with miR-103
      inhibitor significantly suppressed cell proliferation, induced apoptosis,
      inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target
      databases and luciferase reporter assay confirmed that Kruppel-like Factor-4
      (KLF4) was a direct target of miR-103 in GC, and there was a significant inverse
      correlation between miR-103 and KLF4 expression in GC tissues. Moreover, KLF4
      downregulation could rescue miR-103's oncogenic effect on GC cell proliferation,
      apoptosis, migration, and invasion. Therefore, these results suggested that miR
      103 overexpression could contribute to tumor progression by suppressing KLF4, and
      it might serve as a promising candidate for the prognosis of GC patients.

PMID- 28445397
TI  - Radiation and Thyroid Cancer.
AB  - Radiation-induced damage is a complex network of interlinked signaling pathways,
      which may result in apoptosis, cell cycle arrest, DNA repair, and cancer. The
      development of thyroid cancer in response to radiation, from nuclear catastrophes
      to chemotherapy, has long been an object of study. A basic overview of the
      ionizing and non-ionizing radiation effects of the sensitivity of the thyroid
      gland on radiation and cancer development has been provided. In this review, we
      focus our attention on experiments in cell cultures exposed to ionizing
      radiation, ultraviolet light, and proton beams. Studies on the involvement of
      specific genes, proteins, and lipids are also reported. This review also
      describes how lipids are regulated in response to the radiation-induced damage
      and how they are involved in thyroid cancer etiology, invasion, and migration and
      how they can be used as both diagnostic markers and drug targets.

PMID- 28445398
TI  - Consensus-Based Cooperative Control Based on Pollution Sensing and Traffic
      Information for Urban Traffic Networks.
AB  - Nowadays many studies are being conducted to develop solutions for improving the
      performance of urban traffic networks. One of the main challenges is the
      necessary cooperation among different entities such as vehicles or infrastructure
      systems and how to exploit the information available through networks of sensors
      deployed as infrastructures for smart cities. In this work an algorithm for
      cooperative control of urban subsystems is proposed to provide a solution for
      mobility problems in cities. The interconnected traffic lights controller (TLC)
      network adapts traffic lights cycles, based on traffic and air pollution sensory
      information, in order to improve the performance of urban traffic networks. The
      presence of air pollution in cities is not only caused by road traffic but there
      are other pollution sources that contribute to increase or decrease the pollution
      level. Due to the distributed and heterogeneous nature of the different
      components involved, a system of systems engineering approach is applied to
      design a consensus-based control algorithm. The designed control strategy
      contains a consensus-based component that uses the information shared in the
      network for reaching a consensus in the state of TLC network components. Discrete
      event systems specification is applied for modelling and simulation. The proposed
      solution is assessed by simulation studies with very promising results to deal
      with simultaneous responses to both pollution levels and traffic flows in urban
      traffic networks.

PMID- 28445399
TI  - Advances in Psychiatric Diagnosis: Past, Present, and Future.
AB  - This editorial examines controversies identified by the articles in this special
      issue, which explore psychopathology in the broad history of the classification
      of selected psychiatric disorders and syndromes over time through current
      American criteria. Psychiatric diagnosis has a long history of scientific
      investigation and application, with periods of rapid change, instability, and
      heated controversy associated with it. The articles in this issue examine the
      history of psychiatric nomenclature and explore current and future directions in
      psychiatric diagnosis through the various versions of accepted diagnostic
      criteria and accompanying research literature addressing the criteria. The
      articles seek to guide readers in appreciating the complexities of psychiatric
      diagnosis as the field of psychiatry pushes forward toward future advancements in
      diagnosis. Despite efforts of many scientists to advance a diagnostic
      classification system that incorporates neuroscience and genetics, it has been
      argued that it may be premature to attempt to move to a biologically-based
      classification system, because psychiatric disorders cannot yet be fully
      distinguished by any specific biological markers. For now, the symptom-based
      criteria that the field has been using continue to serve many essential purposes,
      including selection of the most effective treatment, communication about disease
      with colleagues, education about psychiatric illness, and support for ongoing
      research.

PMID- 28445400
TI  - Targeting the Epidermal Growth Factor Receptor in Addition to Chemotherapy in
      Patients with Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.
AB  - Overexpression of epidermal growth factor receptors (EGFR) occurs in >90% of
      pancreatic ductal adenocarcinomas (PDACs) and is associated with a poorer
      prognosis. A systematic review of electronic databases identified studies
      exploring the addition of EGFR-targeted treatment to chemotherapy in patients
      with locally advanced (LA)/metastatic PDAC. Efficacy, safety and tolerability of
      EGFR-targeted therapy were explored using meta-analysis of randomised controlled
      trials (RCTs). Meta-regression was utilised to explore factors associated with
      improved prognosis (all studies) and benefit from EGFR-targeted therapy (RCTs).
      Twenty-eight studies (7 RCTs and 21 cohort studies) comprising 3718 patients were
      included. The addition of EGFR-targeted treatment to chemotherapy did not improve
      progression-free (pooled hazard ratio (HR): 0.90, p = 0.15) or overall survival
      (HR: 0.94, p = 0.18). EGFR-targeted therapy was associated with increased
      treatment-related deaths (pooled odds ratio (OR): 5.18, p = 0.007), and grade
      (G)3/4 rash (OR: 4.82, p = 0.03). There was a borderline significant increase in
      G3/4 diarrhoea (OR: 1.75, p = 0.06), but no effect on treatment discontinuation
      without progression (OR: 0.87, p = 0.25). Neither G3/4 rash nor diarrhoea were
      associated with increased survival benefit from EGFR-targeted therapy. The effect
      of EGFR-targeted therapy on overall survival (OS) appeared greater in studies
      with a greater proportion of LA rather than metastatic patients (R = -0.69, p <
      0.001). Further studies in unselected patients with advanced PDAC are not
      warranted. The benefit from EGFR inhibitors may be limited to patient subgroups
      not yet clearly defined.

PMID- 28445401
TI  - Tradeoff-in-the-Nephron: A Theory to Explain the Primacy of Phosphate in the
      Pathogenesis of Secondary Hyperparathyroidism.
AB  - Chronic kidney disease (CKD) causes secondary hyperparathyroidism (SHPT). The
      cardinal features of SHPT are persistence of normocalcemia as CKD progresses and
      dependence of the parathyroid hormone concentration ([PTH]) on phosphate influx
      (IP). The tradeoff-in-the-nephron hypothesis integrates these features. It states
      that as the glomerular filtration rate (GFR) falls, the phosphate concentration
      ([P]CDN) rises in the cortical distal nephron, the calcium concentration
      ([Ca]CDN) in that segment falls, and [PTH] rises to maintain normal calcium
      reabsorption per volume of filtrate (TRCa/GFR). In a clinical study, we set GFR
      equal to creatinine clearance (Ccr) and IP equal to the urinary excretion rate of
      phosphorus (EP). We employed EP/Ccr as a surrogate for [P]CDN. We showed that
      TRCa/Ccr was high in patients with primary hyperparathyroidism (PHPT) and normal
      in those with SHPT despite comparably increased [PTH] in each group. In subjects
      with SHPT, we examined regressions of [PTH] on EP/Ccr before and after treatment
      with sevelamer carbonate or a placebo. All regressions were significant, and
      ?[PTH] correlated with ?EP/Ccr in each treatment cohort. We concluded that [P]CDN
      determines [PTH] in CKD. This inference explains the cardinal features of SHPT,
      much of the evidence on which other pathogenic theories are based, and many
      ancillary observations.

PMID- 28445402
TI  - Synthesis of Gibberellic Acid Derivatives and Their Effects on Plant Growth.
AB  - A series of novel C-3-OH substituted gibberellin derivatives bearing an amide
      group were designed and synthesized from the natural product gibberellic acid
      (GA3). Their activities on the plant growth regulation of rice and Arabidopsis
      were evaluated in vivo. Among these compounds, 10d and 10f exhibited appreciable
      inhibitory activities on rice (48.6% at 100 MUmol/L) and Arabidopsis (41.4% at
      100 MUmol/L), respectively. These results provide new insights into the design
      and synthesis of potential plant growth regulators.

PMID- 28445404
TI  - Support Vector Data Description Model to Map Specific Land Cover with Optimal
      Parameters Determined from a Window-Based Validation Set.
AB  - This paper developed an approach, the window-based validation set for support
      vector data description (WVS-SVDD), to determine optimal parameters for support
      vector data description (SVDD) model to map specific land cover by integrating
      training and window-based validation sets. Compared to the conventional approach
      where the validation set included target and outlier pixels selected visually and
      randomly, the validation set derived from WVS-SVDD constructed a tightened
      hypersphere because of the compact constraint by the outlier pixels which were
      located neighboring to the target class in the spectral feature space. The
      overall accuracies for wheat and bare land achieved were as high as 89.25% and
      83.65%, respectively. However, target class was underestimated because the
      validation set covers only a small fraction of the heterogeneous spectra of the
      target class. The different window sizes were then tested to acquire more wheat
      pixels for validation set. The results showed that classification accuracy
      increased with the increasing window size and the overall accuracies were higher
      than 88% at all window size scales. Moreover, WVS-SVDD showed much less
      sensitivity to the untrained classes than the multi-class support vector machine
      (SVM) method. Therefore, the developed method showed its merits using the optimal
      parameters, tradeoff coefficient (C) and kernel width (s), in mapping homogeneous
      specific land cover.

PMID- 28445403
TI  - Detection of Hepatitis B Virus M204I Mutation by Quantum Dot-Labeled DNA Probe.
AB  - Quantum dots (QDs) are semiconductor nanoparticles with a diameter of less than
      10 nm, which have been widely used as fluorescent probes in biochemical analysis
      and vivo imaging because of their excellent optical properties. Sensitive and
      convenient detection of hepatitis B virus (HBV) gene mutations is important in
      clinical diagnosis. Therefore, we developed a sensitive, low-cost and convenient
      QDs-mediated fluorescent method for the detection of HBV gene mutations in real
      serum samples from chronic hepatitis B (CHB) patients who had received lamivudine
      or telbivudine antiviral therapy. We also evaluated the efficiency of this method
      for the detection of drug-resistant mutations compared with direct sequencing. In
      CHB, HBV DNA from the serum samples of patients with poor response or virological
      breakthrough can be hybridized to probes containing the M204I mutation to
      visualize fluorescence under fluorescence microscopy, where fluorescence
      intensity is related to the virus load, in our method. At present, the limits of
      the method used to detect HBV genetic variations by fluorescence quantum dots is
      103 IU/mL. These results show that QDs can be used as fluorescent probes to
      detect viral HBV DNA polymerase gene variation, and is a simple readout system
      without complex and expensive instruments, which provides an attractive platform
      for the detection of HBV M204I mutation.

PMID- 28445405
TI  - Significant Tic Reduction in An Otherwise Treatment-Resistant Patient with Gilles
      de la Tourette Syndrome Following Treatment with Nabiximols.
AB  - Early anecdotal reports and preliminary studies suggested that cannabinoid-based
      medicines such as delta-9-tetrahydrocannabinol (THC) are effective in the
      treatment of Gilles de la Tourette syndrome (TS). We report a single case study
      of a patient with otherwise treatment-resistant TS successfully treated with
      nabiximols. Our patient was a 22-year-old male suffering from severe and complex
      TS. Treatment with nabiximols was commenced at a dose of 1 puff/day (= 100 MUL
      containing 2.7 mg THC and 2.5 mg cannabidiol (CBD)) and slowly increased up to a
      dosage of 3 * 3 puffs/day (= 24.3 mg THC and 22.5 mg CBD). Several clinical
      measures for tics, premonitory urges, and global impairment were acquired before
      and after two weeks of treatment. Treatment with nabiximols resulted in major
      improvements of both tics and premonitory urges, but also global impairment and
      health-related quality of life according to all used measurements without causing
      relevant adverse effects. Our results provide further evidence that treatment
      with nabiximols may be effective in the treatment of patients with TS. Given the
      positive response exhibited by the patient highlighted in this report, further
      investigation of the effects of nabiximols is proposed on a larger group of
      patients in a clinical trial setting.

PMID- 28445406
TI  - A Pilot Study of Mindfulness Meditation for Pediatric Chronic Pain.
AB  - Despite advances in psychological interventions for pediatric chronic pain, there
      has been little research examining mindfulness meditation for these conditions.
      This study presents data from a pilot clinical trial of a six-week manualized
      mindfulness meditation intervention offered to 20 adolescents aged 13-17 years.
      Measures of pain intensity, functional disability, depression and parent worry
      about their child's pain were obtained at baseline and post-treatment. Results
      indicated no significant changes in pain or depression, however functional
      disability and frequency of pain functioning complaints improved with small
      effect sizes. Parents' worry about child's pain significantly decreased with a
      large effect size. Participants rated intervention components positively and most
      teens suggested that the number of sessions be increased. Three case examples
      illustrate mindfulness meditation effects and precautions. Mindfulness meditation
      shows promise as a feasible and acceptable intervention for youth with chronic
      pain. Future research should optimize intervention components and determine
      treatment efficacy.

PMID- 28445407
TI  - Application of UHPLC-ESI-Q-TOF-MS to Identify Multiple Constituents in Processed
      Products of the Herbal Medicine Ligustri Lucidi Fructus.
AB  - Ligustri Lucidi Fructus (LLF), the fruit of Ligustrum lucidum Ait. (Oleaceae),
      has been used as a common herbal medicine in clinical practice in China for
      nearly 2000 years. In most cases, LLF is prescribed in decoctions in the form of
      processed products rather than crude drugs. In this study, an ultra-high
      performance liquid chromatography coupled with electrospray ionization-quadrupole
      time of flight-mass spectrometry (UHPLC-ESI-Q-TOF-MS) method was established for
      rapid separation and identification of multiple constituents in the 80% methanol
      extract of processed-LLF. A total of 50 compounds (one phenylethanoid, seven
      phenylethanoid glycosides, seven flavonoids, 25 iridoids, nine triterpenoids and
      one cyclohexanecarboxylic acid) were either unambiguously identified or
      tentatively characterized with the aid of authentic standards or published data.
      Luteolin-7-O-rutinoside, oleoside and secologanoside were detected in LLF for the
      first time. This study enriches the chemical profiling of processed-LLF and could
      provide valuable information for the quality control and further investigation of
      processed-LLF and crude LLF.

PMID- 28445409
TI  - Quantification of a Novel Photosensitizer of Chlorin e6-C15-Monomethyl Ester in
      Beagle Dog Plasma Using HPLC: Application to Pharmacokinetic Studies.
AB  - Chlorin e6-C15-monomethyl ester (CMME) is a novel photosensitizer, which is
      synthetized from the degradation products of silkworm excrement. Preclinical
      studies on the promising photosensitizer CMME are necessary to determine its
      therapeutic efficacy and druglikeness. A high-performance liquid chromatography
      with UV detection (HPLC-UV) method was established for the determination of CMME
      in beagle dog plasma. The sample preparation involved a protein-precipitation
      method with acetonitrile after the addition of tanshinone IIA as an internal
      standard (IS). CMME and the IS were separated on a Diamonsil C18 (2) column (100
      mm * 4.6 mm, 5 MUm) with a isocratic system of methanol-water containing 20 mM
      ammonium acetate with 0.3% glacial acetic acid (85:15, v/v). The flow rate was
      1.0 mL/min with UV detection using a wavelength of 400 nm. The method was
      sensitive enough with a lower limit of quantitation (LLOQ) of 0.05 MUg/mL and had
      a good linearity (r2 > 0.999) over the linear range of 0.05-5.00 MUg/mL. The
      intra-day and inter-day accuracies ranged from 98.5% to 102.8% and precisions
      (RSD) were within 6.8%. The validated method was successfully applied to the
      pharmacokinetic study of CMME after intravenous administration of single and
      multiple doses in beagle dogs.

PMID- 28445408
TI  - Algal Proteins: Extraction, Application, and Challenges Concerning Production.
AB  - Population growth combined with increasingly limited resources of arable land and
      fresh water has resulted in a need for alternative protein sources. Macroalgae
      (seaweed) and microalgae are examples of under-exploited "crops". Algae do not
      compete with traditional food crops for space and resources. This review details
      the characteristics of commonly consumed algae, as well as their potential for
      use as a protein source based on their protein quality, amino acid composition,
      and digestibility. Protein extraction methods applied to algae to date, including
      enzymatic hydrolysis, physical processes, and chemical extraction and novel
      methods such as ultrasound-assisted extraction, pulsed electric field, and
      microwave-assisted extraction are discussed. Moreover, existing protein
      enrichment methods used in the dairy industry and the potential of these methods
      to generate high value ingredients from algae, such as bioactive peptides and
      functional ingredients are discussed. Applications of algae in human nutrition,
      animal feed, and aquaculture are examined.

PMID- 28445410
TI  - C-C Coupling Reactions between Benzofurazan Derivatives and 1,3-Diaminobenzenes.
AB  - Aromatic substitution reactions between 1,3-diaminobenzene and
      chloronitrobenzofurazan derivatives have never been reported so far. The aim of
      the current study was to synthesize novel electron-donor and -acceptor
      architectures of interest in applied fields and to provide new insights on the
      nucleophilic behavior of 1,3-diaminobenzenes. The reaction of 1,3-dipiperidinyl-,
      1,3-dimorpholinyl-, 1,3-dipyrrolidinyl-, or 1,3-dimethylamino-benzene with 7
      chloro-4,6-dinitrobenzofuroxan or with a series of chloro-nitrobenzofurazans has
      been carried out in mild conditions. The partners reactivity has been
      investigated by monitoring the reaction course through 1H-NMR spectroscopy. The
      reaction occurred in a regioselective way, providing in good yields the novel C-C
      coupling compounds. Indications on the reactivity behavior for the studied
      nucleophiles have been relieved.

PMID- 28445411
TI  - Discovery of Farnesoid X Receptor Antagonists Based on a Library of Oleanolic
      Acid 3-O-Esters through Diverse Substituent Design and Molecular Docking Methods.
AB  - The pentacyclic triterpene oleanolic acid (OA, 1) with known farnesoid X receptor
      (FXR) modulatory activity was modified at its C-3 position to find new FXR
      interacting agents. A diverse substitution library of OA derivatives was
      constructed in silico through a 2D fingerprint similarity cluster strategy. With
      further docking analysis, four top-scored OA 3-O-ester derivatives were selected
      for synthesis. The bioassay results indicated that all four compounds 3 inhibited
      chenodeoxycholic acid (CDCA)-induced FXR transactivation in a concentration
      dependent mode. Among them 3b and 3d are more active than the parent compound OA.
      A molecular simulation study was performed to attempt to explain the structure
      activity relationship (SAR) and the antagonistic action. To the best of our
      knowledge, this is the first report on semi-synthetic pentacyclic triterpenoids
      with FXR-modulatory activities.

PMID- 28445412
TI  - Assessing the Efficacy of First-Aid Measures in Physalia sp. Envenomation, Using
      Solution- and Blood Agarose-Based Models.
AB  - Stings from the hydrozoan species in the genus Physalia cause intense, immediate
      skin pain and elicit serious systemic effects. There has been much scientific
      debate about the most appropriate first aid for these stings, particularly with
      regard to whether vinegar use is appropriate (most current recommendations
      recommend against vinegar). We found that only a small percentage (<=1.0%) of
      tentacle cnidae discharge during a sting event using an ex vivo tissue model
      which elicits spontaneous stinging from live cnidarian tentacles. We then tested
      a variety of rinse solutions on both Atlantic and Pacific Physalia species to
      determine if they elicit cnidae discharge, further investigating any that did not
      cause immediate significant discharge to determine if they are able to inhibit
      cnidae discharge in response to chemical and physical stimuli. We found
      commercially available vinegars, as well as the recently developed Sting No
      More(r) Spray, were the most effective rinse solutions, as they irreversibly
      inhibited cnidae discharge. However, even slight dilution of vinegar reduced its
      protective effects. Alcohols and folk remedies, such as urine, baking soda and
      shaving cream, caused varying amounts of immediate cnidae discharge and failed to
      inhibit further discharge, and thus likely worsen stings.

PMID- 28445413
TI  - Identification of Highly Specific scFvs against Total Adiponectin for Diagnostic
      Purposes.
AB  - Adiponectin is one of the most abundant adipokines secreted from adipose tissue.
      It acts as an endogenous insulin sensitizer and plasma concentrations are
      inversely correlated with obesity and metabolic syndrome. A decrease in plasma
      adiponectin levels normally indicates increased hormonal activity of the visceral
      lipid tissue, which is associated with decreased insulin sensitivity. It may
      therefore be considered a valuable biomarker for elucidating the underlying
      deteriorations resulting in type 2 diabetes and macrovascular disease. Here we
      present the use of phage display technology to identify highly specific antibody
      fragments (scFvs) against adiponectin. The selected scFvs showed highly specific
      binding to globular and native adiponectin in ELISA tests. By using our phage
      display technology, we were able to obtain monoclonal antibodies with specific
      high affinity binding to the target protein in an effective and easy to upscale
      manner. The selected scFvs against adiponectin can be used for developing
      immunoassays suitable for use in metabolic syndrome diagnosis and monitoring.

PMID- 28445414
TI  - Platform Architecture for Decentralized Positioning Systems.
AB  - A platform architecture for positioning systems is essential for the realization
      of a flexible localization system, which interacts with other systems and
      supports various positioning technologies and algorithms. The decentralized
      processing of a position enables pushing the application-level knowledge into a
      mobile station and avoids the communication with a central unit such as a server
      or a base station. In addition, the calculation of the position on low-cost and
      resource-constrained devices presents a challenge due to the limited computing,
      storage capacity, as well as power supply. Therefore, we propose a platform
      architecture that enables the design of a system with the reusability of the
      components, extensibility (e.g., with other positioning technologies) and
      interoperability. Furthermore, the position is computed on a low-cost device such
      as a microcontroller, which simultaneously performs additional tasks such as data
      collecting or preprocessing based on an operating system. The platform
      architecture is designed, implemented and evaluated on the basis of two
      positioning systems: a field strength system and a time of arrival-based
      positioning system.

PMID- 28445415
TI  - Bioactive Peptides.
AB  - The increased consumer awareness of the health promoting effects of functional
      foods and nutraceuticals is the driving force of the functional food and
      nutraceutical market. Bioactive peptides are known for their high tissue
      affinity, specificity and efficiency in promoting health. For this reason, the
      search for food-derived bioactive peptides has increased exponentially. Over the
      years, many potential bioactive peptides from food have been documented; yet,
      obstacles such as the need to establish optimal conditions for industrial scale
      production and the absence of well-designed clinical trials to provide robust
      evidence for proving health claims continue to exist. Other important factors
      such as the possibility of allergenicity, cytotoxicity and the stability of the
      peptides during gastrointestinal digestion would need to be addressed. This
      review discusses our current knowledge on the health effects of food-derived
      bioactive peptides, their processing methods and challenges in their development.

PMID- 28445417
TI  - INS/GNSS Integration for Aerobatic Flight Applications and Aircraft Motion
      Surveying.
AB  - This paper presents field tests of challenging flight applications obtained with
      a new family of lightweight low-power INS/GNSS (inertial navigation system/global
      satellite navigation system) solutions based on MEMS (micro-electro-mechanical-
      sensor) machined sensors, being used for UAV (unmanned aerial vehicle) navigation
      and control as well as for aircraft motion dynamics analysis and trajectory
      surveying. One key is a 42+ state extended Kalman-filter-based powerful data
      fusion, which also allows the estimation and correction of parameters that are
      typically affected by sensor aging, especially when applying MEMS-based inertial
      sensors, and which is not yet deeply considered in the literature. The paper
      presents the general system architecture, which allows iMAR Navigation the
      integration of all classes of inertial sensors and GNSS (global navigation
      satellite system) receivers from very-low-cost MEMS and high performance MEMS
      over FOG (fiber optical gyro) and RLG (ring laser gyro) up to HRG (hemispherical
      resonator gyro) technology, and presents detailed flight test results obtained
      under extreme flight conditions. As a real-world example, the aerobatic maneuvers
      of the World Champion 2016 (Red Bull Air Race) are presented. Short consideration
      is also given to surveying applications, where the ultimate performance of the
      same data fusion, but applied on gravimetric surveying, is discussed.

PMID- 28445416
TI  - Structure-Function Model for Kissing Loop Interactions That Initiate Dimerization
      of Ty1 RNA.
AB  - The genomic RNA of the retrotransposon Ty1 is packaged as a dimer into virus-like
      particles. The 5' terminus of Ty1 RNA harbors cis-acting sequences required for
      translation initiation, packaging and initiation of reverse transcription
      (TIPIRT). To identify RNA motifs involved in dimerization and packaging, a
      structural model of the TIPIRT domain in vitro was developed from single
      nucleotide resolution RNA structural data. In general agreement with previous
      models, the first 326 nucleotides of Ty1 RNA form a pseudoknot with a 7-bp stem
      (S1), a 1-nucleotide interhelical loop and an 8-bp stem (S2) that delineate two
      long, structured loops. Nucleotide substitutions that disrupt either pseudoknot
      stem greatly reduced helper-Ty1-mediated retrotransposition of a mini-Ty1, but
      only mutations in S2 destabilized mini-Ty1 RNA in cis and helper-Ty1 RNA in
      trans. Nested in different loops of the pseudoknot are two hairpins with
      complementary 7-nucleotide motifs at their apices. Nucleotide substitutions in
      either motif also reduced retrotransposition and destabilized mini- and helper
      Ty1 RNA. Compensatory mutations that restore base-pairing in the S2 stem or
      between the hairpins rescued retrotransposition and RNA stability in cis and
      trans. These data inform a model whereby a Ty1 RNA kissing complex with two
      intermolecular kissing-loop interactions initiates dimerization and packaging.

PMID- 28445419
TI  - Embedded Spherical Localization for Micro Underwater Vehicles Based on
      Attenuation of Electro-Magnetic Carrier Signals.
AB  - Self-localization is one of the most challenging problems for deploying micro
      autonomous underwater vehicles ( MU AUV) in confined underwater environments.
      This paper extends a recently-developed self-localization method that is based on
      the attenuation of electro-magnetic waves, to the MU AUV domain. We demonstrate a
      compact, low-cost architecture that is able to perform all signal processing
      steps present in the original method. The system is passive with one-way signal
      transmission and scales to possibly large MU AUV fleets. It is based on the
      spherical localization concept. We present results from static and dynamic
      position estimation experiments and discuss the tradeoffs of the system.

PMID- 28445418
TI  - Hyponatremia Is Associated with Worse Outcomes from Fall Injuries in the Elderly.
AB  - Background: Hyponatremia has been proposed as a contributor to falls in the
      elderly, which have become a major global issue with the aging of the population.
      This study aimed to assess the clinical presentation and outcomes of elderly
      patients with hyponatremia admitted due to fall injuries in a Level I trauma
      center. Methods: We retrospectively reviewed data obtained from the Trauma
      Registry System for trauma admissions from January 2009 through December 2014.
      Hyponatremia was defined as a serum sodium level <135 mEq/L, and only patients
      who had sustained a fall at ground level (<1 m) were included. We used Chi-square
      tests, Student t-tests, and Mann-Whitney U tests to compare elderly patients (age
      >=65 years) with hyponatremia (n = 492) to those without (n = 2002), and to adult
      patients (age 20-64 years) with hyponatremia (n = 125). Results: Significantly
      more elderly patients with hyponatremia presented to the emergency department
      (ED) due to falls compared to elderly patients without hyponatremia (73.7% vs.
      52.6%; OR: 2.5, 95% CI: 2.10-3.02; p < 0.001). Elderly patients with hyponatremia
      presented with a worse outcome, measured by significantly higher odds of
      intubation (OR: 2.4, 95% CI: 1.15-4.83; p = 0.025), a longer in-hospital length
      of stay (LOS) (11 days vs. 9 days; p < 0.001), higher proportion of intensive
      care unit (ICU) admission (20.9% vs. 16.2%; OR: 1.4, 95% CI: 1.07-1.76; p =
      0.013), and higher mortality (OR: 2.5, 95% CI: 1.53-3.96; p < 0.001), regardless
      of adjustment by Injury Severity Scores (ISS) (AOR: 2.4, 95% CI: 1.42-4.21; p =
      0.001). Conclusions: Our results show that hyponatremia is associated with worse
      outcome from fall-related injuries in the elderly, with an increased ISS, longer
      LOS, and a higher risk of death.

PMID- 28445420
TI  - Vitamin D and Calcium Are Required during Denosumab Treatment in Osteoporosis
      with Rheumatoid Arthritis.
AB  - The aim of this 12-month retrospective study was to evaluate differences in the
      outcomes of denosumab alone or denosumab combined with vitamin D and calcium
      supplementation in patients having osteoporosis (OP) with rheumatoid arthritis
      (RA). Patients were divided into the denosumab monotherapy group (denosumab
      group, 22 cases) or denosumab plus vitamin D supplementation group (combination
      group, 21 cases). We measured serum bone alkaline phosphatase (BAP), N-terminal
      propeptide of type 1 collagen (P1NP), tartrate-resistant acid phosphatase (TRACP)
      5b, and urinary N-terminal telopeptide of type-I collagen (NTX) at baseline, 1
      week, and 1, 2, 4, 6, 8, and 12 months. We also assessed bone mineral density
      (BMD) of the lumbar 1-4 vertebrae (L-BMD) and bilateral total hips (H-BMD) at
      baseline and 4, 8, and 12 months. Matrix metalloprotanase-3 (MMP-3), Disease
      Activity Score-28 C-reactive protein (DAS28-CRP), Simplified Disease Activity
      Index (SDAI), and Health Assessment Questionnaire-Disability Index (HAQ-DI) were
      assessed before treatment and at 12 months to evaluate RA conditions. The study
      results showed that BAP, TRACP-5b, and NTX were significantly decreased, but
      tended to return to pre-treatment levels around 6 and 12 months in both groups.
      While L-BMD and H-BMD substantially increased in both groups, H-BMD had become
      significantly higher in the combination group at 12 months (p < 0.01) as compared
      with the denosumab group. There were no significant differences between the
      groups regarding MMP-3, DAS28-CRP, SDAI, or HAQ-DI. Compared with denosumab
      monotherapy, combination therapy of denosumab with vitamin D and calcium
      significantly increased H-BMD in patients having OP with RA.

PMID- 28445421
TI  - An Improved BLE Indoor Localization with Kalman-Based Fusion: An Experimental
      Study.
AB  - Indoor positioning has grasped great attention in recent years. A number of
      efforts have been exerted to achieve high positioning accuracy. However, there
      exists no technology that proves its efficacy in various situations. In this
      paper, we propose a novel positioning method based on fusing trilateration and
      dead reckoning. We employ Kalman filtering as a position fusion algorithm.
      Moreover, we adopt an Android device with Bluetooth Low Energy modules as the
      communication platform to avoid excessive energy consumption and to improve the
      stability of the received signal strength. To further improve the positioning
      accuracy, we take the environmental context information into account while
      generating the position fixes. Extensive experiments in a testbed are conducted
      to examine the performance of three approaches: trilateration, dead reckoning and
      the fusion method. Additionally, the influence of the knowledge of the
      environmental context is also examined. Finally, our proposed fusion method
      outperforms both trilateration and dead reckoning in terms of accuracy:
      experimental results show that the Kalman-based fusion, for our settings,
      achieves a positioning accuracy of less than one meter.

PMID- 28445422
TI  - Bioactive Components from Qingwen Baidu Decoction against LPS-Induced Acute Lung
      Injury in Rats.
AB  - Qingwen Baidu Decoction (QBD) is an extraordinarily "cold" formula. It was
      traditionally used to cure epidemic hemorrhagic fever, intestinal typhoid fever,
      influenza, sepsis and so on. The purpose of this study was to discover
      relationships between the change of the constituents in different extracts of QBD
      and the pharmacological effect in a rat model of acute lung injury (ALI) induced
      by lipopolysaccharide (LPS). The study aimed to discover the changes in
      constituents of different QBD extracts and the pharmacological effects on acute
      lung injury (ALI) induced by LPS. The results demonstrated that high dose and
      middle dose of QBD had significantly potent anti-inflammatory effects and reduced
      pulmonary edema caused by ALI in rats (p < 0.05). To explore the underlying
      constituents of QBD, we assessed its influence of six different QBD extracts on
      ALI and analyzed the different constituents in the corresponding HPLC
      chromatograms by a Principal Component Analysis (PCA) method. The results showed
      that the pharmacological effect of QBD was related to the polarity of its
      extracts, and the medium polarity extracts E2 and E5 in particular displayed much
      better protective effects against ALI than other groups. Moreover, HPLC-DAD-ESI
      MSn and PCA analysis showed that verbascoside and angoroside C played a key role
      in reducing pulmonary edema. In addition, the current study revealed that ethyl
      gallate, pentagalloylglucose, galloyl paeoniflorin, mudanpioside C and
      harpagoside can treat ALI mainly by reducing the total cells and infiltration of
      activated polymorphonuclear leukocytes (PMNs).

PMID- 28445423
TI  - Anthocyanin Profiles in Flowers of Grape Hyacinth.
AB  - Grape hyacinth (Muscari spp.) is a popular ornamental bulbous perennial famous
      for its blue flowers. To understand the chemical basis of the rich blue colors in
      this plant, anthocyanin profiles of six blue flowering grape hyacinths as well as
      one pink and one white cultivar were determined using high-performance liquid
      chromatography and mass spectrometry. Along with two known compounds, eight
      putative anthocyanins were identified in the tepals of grape hyacinth for the
      first time. The accumulation and distribution of anthocyanins in the plant showed
      significant cultivar and flower development specificity. Violet-blue flowers
      mainly contained simple delphinidin-type anthocyanins bearing one or two methyl
      groups but no acyl groups, whereas white and pink flowers synthesised more
      complex pelargonidin/cyanidin-derivatives with acyl-moieties but no methyl
      groups. The results partially reveal why solid blue, orange or red flowers are
      rare in this plant in nature. In addition, pelargonidin-type anthocyanins were
      found for the first time in the genus, bringing more opportunities in terms of
      breeding of flower color in grape hyacinth.

PMID- 28445424
TI  - The Effect of Deoxynivalenol on Selected Populations of Immunocompetent Cells in
      Porcine Blood-A Preliminary Study.
AB  - Deoxynivalenol (DON) is one of the most prevalent mycotoxins in Europe. Pigs are
      an animal species that is most susceptible to this mycotoxin. Deoxynivalenol
      causes significant losses in pig production by lowering feed intake, decreasing
      daily weight gains, disrupting immune responses, and increasing susceptibility to
      diseases. The aim of this experiment was to determine the influence of feed
      contaminated with DON at concentrations insignificantly higher than recommended
      by the European Commission (900 ug/kg). The experimental feed contained 1008 MUg
      DON/kg. The experiment was performed on eight weaners from the same litter. The
      animals were randomly divided into two groups: an experimental group (M, n = 4)
      fed contaminated feed and a control group (C, n = 4) administered feed free of
      mycotoxins. The experiment lasted for six weeks, and peripheral blood samples
      were collected from the animals for analyses of selected morphological parameters
      and changes in the percentages of CD4+8-, CD4-8+, and CD4+8+ lymphocytes and
      antigen-presenting cells (APC) with CD14+172+ (monocytes), CD172ahigh4-14-
      (conventional dendritic cells, cDC), and CD172adim4+14- (plasmacytoid dendritic
      cells, pDC) phenotypes. The morphological parameters of porcine blood samples
      were determined by flow cytometry with non-fluorescent particle-size calibration
      standards, and no differences were observed between groups M and C. An
      immunophenotyping analysis of lymphocytes and dendritic cells (DC) revealed an
      increase in the percentage of CD4+8-, CD172ahigh4-14-, and CD172adim4+14- cells,
      and a decrease in the number of CD4-8+ cells in group M. The results of this
      experiment suggest that prolonged exposure to low doses of DON can change the
      proportions of immunocompetent cells (a shift towards humoral immunity), without
      affecting their overall counts.

PMID- 28445426
TI  - The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A
      Systematic Review.
AB  - BACKGROUND: Anxiety related conditions are the most common affective disorders
      present in the general population with a lifetime prevalence of over 15%.
      Magnesium (Mg) status is associated with subjective anxiety, leading to the
      proposition that Mg supplementation may attenuate anxiety symptoms. This
      systematic review examines the available evidence for the efficacy of Mg
      supplementation in the alleviation of subjective measures of anxiety and stress.
      METHODS: A systematic search of interventions with Mg alone or in combination (up
      to 5 additional ingredients) was performed in May 2016. Ovid Medline, PsychInfo,
      Embase, CINAHL and Cochrane databases were searched using equivalent search
      terms. A grey literature review of relevant sources was also undertaken. RESULTS:
      18 studies were included in the review. All reviewed studies recruited samples
      based upon an existing vulnerability to anxiety: mildly anxious, premenstrual
      syndrome (PMS), postpartum status, and hypertension. Four/eight studies in
      anxious samples, four/seven studies in PMS samples, and one/two studies in
      hypertensive samples reported positive effects of Mg on subjective anxiety
      outcomes. Mg had no effect on postpartum anxiety. No study administered a
      validated measure of subjective stress as an outcome. CONCLUSIONS: Existing
      evidence is suggestive of a beneficial effect of Mg on subjective anxiety in
      anxiety vulnerable samples. However, the quality of the existing evidence is
      poor. Well-designed randomised controlled trials are required to further confirm
      the efficacy of Mg supplementation.

PMID- 28445425
TI  - Association of Long-Term Near-Highway Exposure to Ultrafine Particles with
      Cardiovascular Diseases, Diabetes and Hypertension.
AB  - Ultrafine particle (UFP) concentrations are elevated near busy roadways, however,
      their effects on prevalence of cardiovascular diseases, diabetes, and
      hypertension are not well understood. To investigate these associations, data on
      demographics, diseases, medication use, and time of activities were collected by
      in-home surveys for 704 participants in three pairs of near-highway and urban
      background neighborhoods in and near Boston (MA, USA). Body mass index (BMI) was
      measured for a subset of 435 participants. Particle number concentration (PNC, a
      measure of UFP) was collected by mobile monitoring in each area. Intra
      neighborhood spatial-temporal regression models (approximately 20 m resolution)
      were used to estimate hourly ambient PNC at the residences of participants. We
      used participant time activity information to adjust annual average residential
      PNC values and assign individualized time activity adjusted annual average PNC
      exposures (TAA-PNC). Using multivariate logistic regression models, we found an
      odds ratio (OR) of 1.35 (95% CI: 0.83, 2.22) of TAA-PNC with stroke and ischemic
      heart diseases (S/IHD), an OR of 1.14 (95% CI: 0.81, 1.62) with hypertension, and
      an OR of 0.71 (95% CI: 0.46, 1.10) for diabetes. A subset analysis controlling
      for BMI produced slightly stronger associations for S/IHD (OR = 1.61, 95% CI:
      0.88, 2.92) and hypertension (OR = 1.28, 95% CI: 0.81, 2.02), and no association
      with diabetes (OR = 1.09, 95% CI = 0.61, 1.96). Further research is needed with
      larger sample sizes and longitudinal follow-up.

PMID- 28445427
TI  - Small RNA Pathways That Protect the Somatic Genome.
AB  - Transposable elements (TEs) are DNA elements that can change their position
      within the genome, with the potential to create mutations and destabilize the
      genome. As such, special molecular systems have been adopted in animals to
      control TE activity in order to protect the genome. PIWI proteins, in
      collaboration with PIWI-interacting RNAs (piRNAs), are well known to play a
      critical role in silencing germline TEs. Although initially thought to be
      germline-specific, the role of PIWI-piRNA pathways in controlling TEs in somatic
      cells has recently begun to be explored in various organisms, together with the
      role of endogenous small interfering RNAs (endo-siRNAs). This review summarizes
      recent results suggesting that these small RNA pathways have been critically
      implicated in the silencing of somatic TEs underlying various physiological
      traits, with a special focus on the Drosophila model organism.

PMID- 28445429
TI  - Exploring the Behavioral and Metabolic Phenotype Generated by Re-Introduction of
      the Ghrelin Receptor in the Ventral Tegmental Area.
AB  - Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA)
      can modulate dopaminergic function and the reward-related effects of both
      palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in
      VTA neurons in Ghr-R knockout mice (Ghr-RVTA mice) to specifically study the
      importance of the constitutively active Ghr-R for VTA neuronal signaling. Our
      results showed that re-introduction of the Ghr-R in the VTA had no impact on body
      weight or food intake under basal conditions. However, during novel environment
      stress Ghr-RVTA mice showed increased food intake and energy expenditure compared
      to Ghr-R knockout mice, demonstrating the significance of Ghr-R signaling in the
      response to stress. Ghr-RVTA mice also showed increased cocaine-induced locomotor
      activity compared to Ghr-R knockout mice, highlighting the importance of ghrelin
      signaling for the reward-related effects of activation of VTA neurons. Overall,
      our data suggest that re-introduction of the Ghr-R in the mesolimbic reward
      system of Ghr-R knockout mice increases the level of activation induced by both
      cocaine and novelty stress.

PMID- 28445428
TI  - Residue Modification and Mass Spectrometry for the Investigation of Structural
      and Metalation Properties of Metallothionein and Cysteine-Rich Proteins.
AB  - Structural information regarding metallothioneins (MTs) has been hard to come by
      due to its highly dynamic nature in the absence of metal-thiolate cluster
      formation and crystallization difficulties. Thus, typical spectroscopic methods
      for structural determination are limited in their usefulness when applied to MTs.
      Mass spectrometric methods have revolutionized our understanding of protein
      dynamics, structure, and folding. Recently, advances have been made in residue
      modification mass spectrometry in order to probe the hard-to-characterize
      structure of apo- and partially metalated MTs. By using different cysteine
      specific alkylation reagents, time dependent electrospray ionization mass
      spectrometry (ESI-MS), and step-wise "snapshot" ESI-MS, we are beginning to
      understand the dynamics of the conformers of apo-MT and related species. In this
      review we highlight recent papers that use these and similar techniques for
      structure elucidation and attempt to explain in a concise manner the data
      interpretations of these complex methods. We expect increasing resolution in our
      picture of the structural conformations of metal-free MTs as these techniques are
      more widely adopted and combined with other promising tools for structural
      elucidation.

PMID- 28445431
TI  - Assessing Diabetes and Factors Associated with Foregoing Medical Care among
      Persons with Diabetes: Disparities Facing American Indian/Alaska Native, Black,
      Hispanic, Low Income, and Southern Adults in the U.S. (2011-2015).
AB  - Objective: Identify individual- and place-based factors associated with diagnosed
      diabetes and forgone medical care among those diagnosed with diabetes.
      Background: Diabetes affects millions of individuals globally. In the U.S. alone
      the prevalence rate of diagnosed diabetes has more than doubled over the past 20
      years (4.2% in 1994 to 10% in 2014). Methods: The Behavioral Risk Factor
      Surveillance System (2011-2015) was used to identify factors associated with self
      reported diabetes diagnoses (ever diagnosed) among U.S. adults. Logistic
      regression modeled: (1) the likelihood of having diabetes; (2) the likelihood of
      forgone medical care among those with diabetes, given appropriate medical care
      has been linked to preventing complications associated with diabetes. Results:
      Rates of diabetes remained relatively stable from 2011 to 2015. The likelihood of
      diabetes was higher (p < 0.01) among racial and ethnic minority groups, men,
      those with lower incomes and those with lower education. Place-based disparities
      indicating a higher likelihood of having a diagnosis of diabetes were found for
      those living in rural areas (urban versus rural, unadjusted OR = 0.844-0.908; p <
      0.01) and those living in the South (North, Midwest, and Western/Pacific regions
      versus the South, unadjusted OR = 0.794-0.889; p < 0.01). Similar results were
      found with forgone medical care among those diagnosed with diabetes being more
      likely in the South (North, Midwest, and Western/Pacific regions versus the
      South, unadjusted OR = 0.542-0.819). In fully-adjusted analyses, the prevalence
      of diabetes and forgone medical care among those diagnosed with diabetes was
      higher for those with lower incomes, from several racial/ethnic minority groups,
      and in the South versus most other regions. Conclusions: Identifying at-risk
      groups informs targets for prevention and assists efforts to address chronic
      disease self-management among those already diagnosed with diabetes.

PMID- 28445430
TI  - Impact of Land Use on PM2.5 Pollution in a Representative City of Middle China.
AB  - Fine particulate matter (PM2.5) pollution has become one of the greatest urban
      issues in China. Studies have shown that PM2.5 pollution is strongly related to
      the land use pattern at the micro-scale and optimizing the land use pattern has
      been suggested as an approach to mitigate PM2.5 pollution. However, there are
      only a few researches analyzing the effect of land use on PM2.5 pollution. This
      paper employed land use regression (LUR) models and statistical analysis to
      explore the effect of land use on PM2.5 pollution in urban areas. Nanchang city,
      China, was taken as the study area. The LUR models were used to simulate the
      spatial variations of PM2.5 concentrations. Analysis of variance and multiple
      comparisons were employed to study the PM2.5 concentration variances among five
      different types of urban functional zones. Multiple linear regression was applied
      to explore the PM2.5 concentration variances among the same type of urban
      functional zone. The results indicate that the dominant factor affecting PM2.5
      pollution in the Nanchang urban area was the traffic conditions. Significant
      variances of PM2.5 concentrations among different urban functional zones
      throughout the year suggest that land use types generated a significant impact on
      PM2.5 concentrations and the impact did not change as the seasons changed. Land
      use intensity indexes including the building volume rate, building density, and
      green coverage rate presented an insignificant or counter-intuitive impact on
      PM2.5 concentrations when studied at the spatial scale of urban functional zones.
      Our study demonstrates that land use can greatly affect the PM2.5 levels.
      Additionally, the urban functional zone was an appropriate spatial scale to
      investigate the impact of land use type on PM2.5 pollution in urban areas.

PMID- 28445432
TI  - Multispectral LiDAR Data for Land Cover Classification of Urban Areas.
AB  - Airborne Light Detection And Ranging (LiDAR) systems usually operate at a
      monochromatic wavelength measuring the range and the strength of the reflected
      energy (intensity) from objects. Recently, multispectral LiDAR sensors, which
      acquire data at different wavelengths, have emerged. This allows for recording of
      a diversity of spectral reflectance from objects. In this context, we aim to
      investigate the use of multispectral LiDAR data in land cover classification
      using two different techniques. The first is image-based classification, where
      intensity and height images are created from LiDAR points and then a maximum
      likelihood classifier is applied. The second is point-based classification, where
      ground filtering and Normalized Difference Vegetation Indices (NDVIs) computation
      are conducted. A dataset of an urban area located in Oshawa, Ontario, Canada, is
      classified into four classes: buildings, trees, roads and grass. An overall
      accuracy of up to 89.9% and 92.7% is achieved from image classification and 3D
      point classification, respectively. A radiometric correction model is also
      applied to the intensity data in order to remove the attenuation due to the
      system distortion and terrain height variation. The classification process is
      then repeated, and the results demonstrate that there are no significant
      improvements achieved in the overall accuracy.

PMID- 28445434
TI  - An Adaptive Clustering Approach Based on Minimum Travel Route Planning for
      Wireless Sensor Networks with a Mobile Sink.
AB  - In recent years, Wireless Sensor Networks with a Mobile Sink (WSN-MS) have been
      an active research topic due to the widespread use of mobile devices. However,
      how to get the balance between data delivery latency and energy consumption
      becomes a key issue of WSN-MS. In this paper, we study the clustering approach by
      jointly considering the Route planning for mobile sink and Clustering Problem
      (RCP) for static sensor nodes. We solve the RCP problem by using the minimum
      travel route clustering approach, which applies the minimum travel route of the
      mobile sink to guide the clustering process. We formulate the RCP problem as an
      Integer Non-Linear Programming (INLP) problem to shorten the travel route of the
      mobile sink under three constraints: the communication hops constraint, the
      travel route constraint and the loop avoidance constraint. We then propose an
      Imprecise Induction Algorithm (IIA) based on the property that the solution with
      a small hop count is more feasible than that with a large hop count. The IIA
      algorithm includes three processes: initializing travel route planning with a
      Traveling Salesman Problem (TSP) algorithm, transforming the cluster head to a
      cluster member and transforming the cluster member to a cluster head. Extensive
      experimental results show that the IIA algorithm could automatically adjust
      cluster heads according to the maximum hops parameter and plan a shorter travel
      route for the mobile sink. Compared with the Shortest Path Tree-based Data
      Gathering Algorithm (SPT-DGA), the IIA algorithm has the characteristics of
      shorter route length, smaller cluster head count and faster convergence rate.

PMID- 28445435
TI  - Microarray Selection of Cooperative Peptides for Modulating Enzyme Activities.
AB  - Recently, peptide microarrays have been used to distinguish proteins, antibodies,
      viruses, and bacteria based on their binding to random sequence peptides. We
      reported on the use of peptide arrays to identify enzyme modulators that involve
      screening an array of 10,000 defined and addressable peptides on a microarray.
      Primary peptides were first selected to inhibit the enzyme at low MUM
      concentrations. Then, new peptides were found to only bind strongly with the
      enzyme-inhibitor complex, but not the native enzyme. These new peptides served as
      secondary inhibitors that enhanced the inhibition of the enzyme together with the
      primary peptides. Without the primary peptides, the secondary effect peptides had
      little effect on the enzyme activity. Conversely, we also selected peptides that
      recovered the activities of inhibited enzyme-peptide complex. The selection of
      cooperative peptide pairs will provide a versatile toolkit for modulating enzyme
      functions, which may potentially be applied to drug discovery and biocatalysis.

PMID- 28445433
TI  - Determinants of Work Performance in Workers with Depression and Anxiety: A Cross
      Sectional Study.
AB  - Depression and anxiety are highly prevalent disorders with an impact on
      existential aspects of person's life, including employment i.e., work performance
      (WP). In order to develop appropriate strategies, it is essential to identify
      determinants of WP. The objective of this study was to identify the built,
      social, attitudinal and health system-related environmental determinants of WP in
      workers with anxiety or depression in total (N = 1211) and regarding the level of
      disability. Hierarchical binary logistic regression was performed on data
      obtained from implementation of the WHO Model Disability Survey (MDS) in Chile in
      2015. Hindering aspects of means of transportation and workplace, and the use of
      personal assistance were determinants of WP for all workers with anxiety or
      depression. Results differed with level of disability. Hindering aspects of means
      of transportation and workplace, and discrimination were determinants of WP for
      persons with mild to moderate disability, while hindering aspects of the
      workplace and dwelling, and the use of personal assistance were determinants of
      WP for persons with severe disability. Our results emphasize the need for a
      broader understanding of determinants of WP and the requirement for an
      integrative approach in developing both universal and specific strategies that go
      beyond workplace settings.

PMID- 28445436
TI  - Irritable Bowel Syndrome: Clinical Manifestations, Dietary Influences, and
      Management.
AB  - Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is
      characterized by symptoms of chronic abdominal pain and altered bowel habits in
      the absence of an overtly identifiable cause. It is the most commonly diagnosed
      functional gastrointestinal disorder, accounting for about one third of
      gastroenterology visits. It generally presents as a complex of symptoms,
      including psychological dysfunction. Hypersensitivity to certain foods,
      especially foods that contain high amounts of fructose, plays a role in the
      pathophysiology of IBS. Elevated consumption of high-fructose corn syrup (HFCS)
      has been discussed in this aspect. The treatment options for IBS are challenging
      and varied. In addition to dietary restrictions for HFCS-induced IBS, such as low
      FODMAP (Fermentable Oligosaccharides, Disaccharide, Monosaccharides, and Polyols)
      diets, existing drug therapies are administered based on the predominant symptoms
      and IBS-subtype. Patients with IBS are likely to suffer from issues, such as
      anxiety, depression, and post-traumatic-stress disorder. Biopsychosocial factors
      particularly socioeconomic status, sex, and race should, thus, be considered for
      diagnostic evaluation of patients with IBS.

PMID- 28445437
TI  - An Exploratory Study on the Influence of Psychopathological Risk and Impulsivity
      on BMI and Perceived Quality of Life in Obese Patients.
AB  - The present study aimed to assess the psychological profiles of adult male and
      female obese patients, as well as to verify the possible influence of their
      psychopathological risk and impulsivity on their body mass index (BMI) and
      perceived quality of life. A total of 64 obese subjects accessing a center for
      care of their obesity were assessed through anthropometric and psychometric
      measurements. All anthropometric measures in men were higher than in women, while
      in turn, women showed higher psychopathological symptoms. Furthermore, the
      symptoms of somatization and psychoticism were predictors for a higher BMI in
      men, but there was no effect of psychopathological symptoms on the perceived
      quality of life (QoL) of male subjects. Moreover, in women, somatization and
      attentional impulsivity were predictors for a higher BMI, whereas no correlation
      was found between their psychopathological risk and perceived QoL. The results of
      regression analysis underlined that somatization is a "core" psychopathological
      symptom in obese subjects regardless of their sex, which is a potential predictor
      for a higher BMI. The psychological difficulties of the subjects had no effect on
      their perceived QoL, suggesting that they find it difficult to reflect on the
      impact that obesity has on their life.

PMID- 28445438
TI  - Reliability and Validity of the Medical Outcomes Study Short Form-12 Version 2
      (SF-12v2) in Adults with Non-Cancer Pain.
AB  - Limited evidence exists on how non-cancer pain (NCP) affects an individual's
      health-related quality of life (HRQoL). This study aimed to validate the Medical
      Outcomes Study Short Form-12 Version 2 (SF-12v2), a generic measure of HRQoL, in
      a NCP cohort using the Medical Expenditure Panel Survey Longitudinal Files. The
      SF Mental Component Summary (MCS12) and SF Physical Component Summary (PCS12)
      were tested for reliability (internal consistency and test-retest reliability)
      and validity (construct: convergent and discriminant; criterion: concurrent and
      predictive). A total of 15,716 patients with NCP were included in the final
      analysis. The MCS12 and PCS12 demonstrated high internal consistency (Cronbach's
      alpha and Mosier's alpha > 0.8), and moderate and high test-retest reliability,
      respectively (MCS12 intraclass correlation coefficient (ICC): 0.64; PCS12 ICC:
      0.73). Both scales were significantly associated with a number of chronic
      conditions (p < 0.05). The PCS12 was strongly correlated with perceived health (r
      = 0.52) but weakly correlated with perceived mental health (r = 0.25). The MCS12
      was moderately correlated with perceived mental health (r = 0.42) and perceived
      health (r = 0.33). Increasing PCS12 and MCS12 scores were significantly
      associated with lower odds of reporting future physical and cognitive limitations
      (PCS12: OR = 0.90 95%CI: 0.89-0.90, MCS12: OR = 0.94 95%CI: 0.93-0.94). In
      summary, the SF-12v2 is a reliable and valid measure of HRQoL for patients with
      NCP.

PMID- 28445441
TI  - Mining Productive-Associated Periodic-Frequent Patterns in Body Sensor Data for
      Smart Home Care.
AB  - The understanding of various health-oriented vital sign data generated from body
      sensor networks (BSNs) and discovery of the associations between the generated
      parameters is an important task that may assist and promote important decision
      making in healthcare. For example, in a smart home scenario where occupants'
      health status is continuously monitored remotely, it is essential to provide the
      required assistance when an unusual or critical situation is detected in their
      vital sign data. In this paper, we present an efficient approach for mining the
      periodic patterns obtained from BSN data. In addition, we employ a correlation
      test on the generated patterns and introduce productive-associated periodic
      frequent patterns as the set of correlated periodic-frequent items. The
      combination of these measures has the advantage of empowering healthcare
      providers and patients to raise the quality of diagnosis as well as improve
      treatment and smart care, especially for elderly people in smart homes. We
      develop an efficient algorithm named PPFP-growth (Productive Periodic-Frequent
      Pattern-growth) to discover all productive-associated periodic frequent patterns
      using these measures. PPFP-growth is efficient and the productiveness measure
      removes uncorrelated periodic items. An experimental evaluation on synthetic and
      real datasets shows the efficiency of the proposed PPFP-growth algorithm, which
      can filter a huge number of periodic patterns to reveal only the correlated ones.

PMID- 28445440
TI  - Micronutrient Status among Pregnant Women in Zinder, Niger and Risk Factors
      Associated with Deficiency.
AB  - Anemia and micronutrient (MN) deficiencies in pregnant women are associated with
      adverse pregnancy outcomes. In Niger, 58.6% of pregnant women are anemic;
      however, MN statuses are unknown. The study objectives were to estimate the
      prevalence of MN deficiencies among pregnant women in Zinder, Niger and explore
      associated risk factors. Pregnant women living in randomly selected rural
      villages (n = 88) were included. Capillary and venous blood samples (n = 770)
      were analyzed for hemoglobin (Hb) and plasma ferritin, soluble transferrin
      receptor (sTfR), zinc (pZn), retinol binding protein (RBP), folate and vitamin
      B12. C-reactive protein and alpha-1-acid glycoprotein were measured to adjust for
      inflammation. The prevalence of MN deficiencies in pregnant woman was high,
      indicative of a severe public health problem. Prevalence of iron deficiency was
      20.7% and 35.7%, by ferritin (<15 ug/L) and sTfR (>8.3 mg/L), respectively. In
      total, 40.7% of women had low pZn (<50 ug/dL), 79.7% had marginal RBP (<1.32
      umol/L), 44.3% of women had low folate (<10 nmol/L) and 34.8% had low B12
      concentrations (<148 pmol/L). Common risk factors associated with MN status
      included gravidity, mid-upper-arm circumference, geophagy, malaria, and result of
      the woman's last pregnancy. Interventions to promote the strengthening of
      antenatal care, and access and adherence to nutrition and health interventions
      are critical among pregnant women in this population.

PMID- 28445442
TI  - A Review Study on Macrolides Isolated from Cyanobacteria.
AB  - Cyanobacteria are rich sources of structurally-diverse molecules with promising
      pharmacological activities. Marine cyanobacteria have been proven to be true
      producers of some significant bioactive metabolites from marine invertebrates.
      Macrolides are a class of bioactive compounds isolated from marine organisms,
      including marine microorganisms in particular. The structural characteristics of
      macrolides from cyanobacteria mainly manifest in the diversity of carbon
      skeletons, complexes of chlorinated thiazole-containing molecules and complex
      spatial configuration. In the present work, we systematically reviewed the
      structures and pharmacological activities of macrolides from cyanobacteria. Our
      data would help establish an effective support system for the discovery and
      development of cyanobacterium-derived macrolides.

PMID- 28445439
TI  - HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab
      Resistance.
AB  - HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all
      breast cancers (BCs) is a poor prognosis factor and a precious target for BC
      therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating
      HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo
      resistance to trastuzumab, partially due to the loss of expression of HER2
      extracellular domain on their tumor cells. This is due to shedding/cleavage of
      HER2 by metalloproteinases (ADAMs and MMPs). HER2 shedding results in the
      accumulation of intracellular carboxyl-terminal HER2 (p95HER2), which is a common
      phenomenon in trastuzumab-resistant tumors and is suggested as a predictive
      marker for trastuzumab resistance. Up-regulation of the metalloproteinases is a
      poor prognosis factor and is commonly seen in mesenchymal-like cancer stem cells
      that are risen during epithelial to mesenchymal transition (EMT) of tumor cells.
      HER2 cleavage during EMT can explain why secondary metastatic tumors with high
      percentage of mesenchymal-like cancer stem cells are mostly resistant to
      trastuzumab but still sensitive to lapatinib. Importantly, many studies report
      HER2 interaction with oncogenic/stemness signaling pathways including TGF
      beta/Smad, Wnt/beta-catenin, Notch, JAK/STAT and Hedgehog. HER2 overexpression
      promotes EMT and the emergence of cancer stem cell properties in BC. Increased
      expression and activation of metalloproteinases during EMT leads to proteolytic
      cleavage and shedding of HER2 receptor, which downregulates HER2 extracellular
      domain and eventually increases trastuzumab resistance. Here, we review the
      hypothesis that a negative feedback loop between HER2 and stemness signaling
      drives resistance of BC to trastuzumab.

PMID- 28445444
TI  - Pharmaceutical Equivalence of Clarithromycin Oral Dosage Forms Marketed in
      Nairobi County, Kenya.
AB  - Clarithromycin is a broad-spectrum semi-synthetic macrolide indicated for
      treatment of pneumonias, Helicobacter pylori, and chlamydial and skin infections.
      The object of this study was to evaluate the pharmaceutical equivalence of 14
      generic clarithromycin products marketed in Nairobi County, Kenya, to the
      innovator products, using in vitro dissolution profiles and similarity factors
      (f2). Further, dissolution profiles of four innovator formulations manufactured
      in different sites were compared. Fourteen clarithromycin tablets/capsules and
      four suspensions were subjected to assay and comparative dissolution runs at pH
      1.2, 4.5 and 6.8, for 60 and 90 min, respectively. All products complied with
      pharmacopoeial assay specifications. However, significant differences were
      observed in their dissolution profiles. The non-compliance rates for
      tablets/capsules were 50% at pH 1.2, 33% at pH 4.5 and 50% at pH 6.8, while none
      of the four suspensions were compliant. Overall, only four (25%) products
      complied with the specifications for similarity factor. The results obtained
      indicate that a significant percentage of generic clarithromycin products are
      pharmaceutically non-equivalent to the innovator products, and that assay and
      single-point dissolution tests are insufficient demonstration of equivalence
      between the generic and innovator products.

PMID- 28445446
TI  - Sustainability: A meaty issue.

PMID- 28445443
TI  - NutrimiRAging: Micromanaging Nutrient Sensing Pathways through Nutrition to
      Promote Healthy Aging.
AB  - Current sociodemographic predictions point to a demographic shift in developed
      and developing countries that will result in an unprecedented increase of the
      elderly population. This will be accompanied by an increase in age-related
      conditions that will strongly impair human health and quality of life. For this
      reason, aging is a major concern worldwide. Healthy aging depends on a
      combination of individual genetic factors and external environmental factors.
      Diet has been proved to be a powerful tool to modulate aging and caloric
      restriction has emerged as a valuable intervention in this regard. However, many
      questions about how a controlled caloric restriction intervention affects aging
      related processes are still unanswered. Nutrient sensing pathways become
      deregulated with age and lose effectiveness with age. These pathways are a link
      between diet and aging. Thus, fully understanding this link is a mandatory step
      before bringing caloric restriction into practice. MicroRNAs have emerged as
      important regulators of cellular functions and can be modified by diet. Some
      microRNAs target genes encoding proteins and enzymes belonging to the nutrient
      sensing pathways and, therefore, may play key roles in the modulation of the
      aging process. In this review, we aimed to show the relationship between diet,
      nutrient sensing pathways and microRNAs in the context of aging.

PMID- 28445445
TI  - Cardioprotective Effects of Malvidin Against Isoproterenol-Induced Myocardial
      Infarction in Rats: A Mechanistic Study.
AB  - BACKGROUND Malvidin (alvidin-3-glucoside) is a polyphenol that belongs to the
      class of natural anthocyanin, which is abundantly found in red wines, colored
      fruits, and the skin of red grapes. Therefore, the current investigation was
      intended to evaluate the effect of malvidin against myocardial infarction induced
      by isoproterenol in the rats. MATERIAL AND METHODS The cardioprotective effects
      was assessed by determining the effect of malvidin on the activities of
      endogenous antioxidants - catalase (CAT), superoxide dismutase (SOD), and
      glutathione peroxidase (GSH) - and on the levels of lipid peroxidation and serum
      marker enzymes. The serum levels of IL-6 and TNF-alpha were also determined using
      an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS The present study
      demonstrated a significant cardioprotective effect of malvidin by restoring the
      defensive activities of endogenous antioxidants - catalase (CAT), superoxide
      dismutase (SOD), and glutathione peroxidase (GSH) - and by reducing the levels of
      lipid peroxidation and serum marker enzymes lactate dehydrogenase (LD) and
      creatine kinase (CK). Malvidin significantly ameliorated the histopathological
      changes and impaired mitochondria in the cardiac necrosis stimulated with
      isoproterenol. Additionally, the results also demonstrated that nuclear
      translocation of Nrf-2 and subsequent HO-1 expression might be associated with
      nuclear factor kappa B (NF-kappaB) pathway activation. CONCLUSIONS Our findings
      suggest that malvidin exerts cardioprotective effects that might be due to
      possible strong antioxidant and anti-inflammatory activities. Therefore, this
      study provides the basis for the development of malvidin as a safe and effective
      treatment of myocardial infarction.

PMID- 28445447
TI  - Food security.

PMID- 28445448
TI  - Nutrition: A world of insecurity.

PMID- 28445449
TI  - Agrobiodiversity: The living library.

PMID- 28445450
TI  - Technology: The Future of Agriculture.

PMID- 28445451
TI  - Bioengineering: Solar upgrade.

PMID- 28445452
TI  - Egypt: Space to grow.

PMID- 28445453
TI  - Perspective: Look beyond production.

PMID- 28445454
TI  - Body composition at birth and its relationship with neonatal anthropometric
      ratios: the newborn body composition study of the INTERGROWTH-21st project.
AB  - BackgroundWe aimed to describe newborn body composition and identify which
      anthropometric ratio (weight/length; BMI; or ponderal index, PI) best predicts
      fat mass (FM) and fat-free mass (FFM).MethodsAir-displacement plethysmography
      (PEA POD) was used to estimate FM, FFM, and body fat percentage (BF%).
      Associations between FFM, FM, and BF% and weight/length, BMI, and PI were
      evaluated in 1,019 newborns using multivariate regression analysis. Charts for
      FM, FFM, and BF% were generated using a prescriptive subsample (n=247). Standards
      for the best-predicting anthropometric ratio were calculated utilizing the same
      population used for the INTERGROWTH-21st Newborn Size Standards
      (n=20,479).ResultsFFM and FM increased consistently during late pregnancy.
      Differential FM, BF%, and FFM patterns were observed for those born preterm (34+0
      36+6 weeks' gestation) and with impaired intrauterine growth. Weight/length by
      gestational age (GA) was a better predictor of FFM and FM (adjusted R2=0.92 and
      0.71, respectively) than BMI or PI, independent of sex, GA, and timing of
      measurement. Results were almost identical when only preterm newborns were
      studied. We present sex-specific centiles for weight/length ratio for
      GA.ConclusionsWeight/length best predicts newborn FFM and FM. There are
      differential FM, FFM, and BF% patterns by sex, GA, and size at birth.

PMID- 28445455
TI  - Structural insight into allosteric modulation of protease-activated receptor 2.
AB  - Protease-activated receptors (PARs) are a family of G-protein-coupled receptors
      (GPCRs) that are irreversibly activated by proteolytic cleavage of the N
      terminus, which unmasks a tethered peptide ligand that binds and activates the
      transmembrane receptor domain, eliciting a cellular cascade in response to
      inflammatory signals and other stimuli. PARs are implicated in a wide range of
      diseases, such as cancer and inflammation. PARs have been the subject of major
      pharmaceutical research efforts but the discovery of small-molecule antagonists
      that effectively bind them has proved challenging. The only marketed drug
      targeting a PAR is vorapaxar, a selective antagonist of PAR1 used to prevent
      thrombosis. The structure of PAR1 in complex with vorapaxar has been reported
      previously. Despite sequence homology across the PAR isoforms, discovery of PAR2
      antagonists has been less successful, although GB88 has been described as a weak
      antagonist. Here we report crystal structures of PAR2 in complex with two
      distinct antagonists and a blocking antibody. The antagonist AZ8838 binds in a
      fully occluded pocket near the extracellular surface. Functional and binding
      studies reveal that AZ8838 exhibits slow binding kinetics, which is an attractive
      feature for a PAR2 antagonist competing against a tethered ligand. Antagonist
      AZ3451 binds to a remote allosteric site outside the helical bundle. We propose
      that antagonist binding prevents structural rearrangements required for receptor
      activation and signalling. We also show that a blocking antibody antigen-binding
      fragment binds to the extracellular surface of PAR2, preventing access of the
      tethered ligand to the peptide-binding site. These structures provide a basis for
      the development of selective PAR2 antagonists for a range of therapeutic uses.

PMID- 28445456
TI  - Floor-plate-derived netrin-1 is dispensable for commissural axon guidance.
AB  - Netrin-1 is an evolutionarily conserved, secreted extracellular matrix protein
      involved in axon guidance at the central nervous system midline. Netrin-1 is
      expressed by cells localized at the central nervous system midline, such as those
      of the floor plate in vertebrate embryos. Growth cone turning assays and three
      dimensional gel diffusion assays have shown that netrin-1 can attract commissural
      axons. Loss-of-function experiments further demonstrated that commissural axon
      extension to the midline is severely impaired in the absence of netrin-1 (refs 3,
      7, 8, 9). Together, these data have long supported a model in which commissural
      axons are attracted by a netrin-1 gradient diffusing from the midline. Here we
      selectively ablate netrin-1 expression in floor-plate cells using a Ntn1
      conditional knockout mouse line. We find that hindbrain and spinal cord
      commissural axons develop normally in the absence of floor-plate-derived netrin
      1. Furthermore, we show that netrin-1 is highly expressed by cells in the
      ventricular zone, which can release netrin-1 at the pial surface where it binds
      to commissural axons. Notably, Ntn1 deletion from the ventricular zone
      phenocopies commissural axon guidance defects previously described in Ntn1
      knockout mice. These results show that the classical view that attraction of
      commissural axons is mediated by a gradient of floor-plate-derived netrin-1 is
      inaccurate and that netrin-1 primarily acts locally by promoting growth cone
      adhesion.

PMID- 28445458
TI  - Neurodegeneration: Role of repeats in protein clearance.

PMID- 28445457
TI  - The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and
      viability.
AB  - Mitochondrial calcium (mCa2+) has a central role in both metabolic regulation and
      cell death signalling, however its role in homeostatic function and disease is
      controversial. Slc8b1 encodes the mitochondrial Na+/Ca2+ exchanger (NCLX), which
      is proposed to be the primary mechanism for mCa2+ extrusion in excitable cells.
      Here we show that tamoxifen-induced deletion of Slc8b1 in adult mouse hearts
      causes sudden death, with less than 13% of affected mice surviving after 14 days.
      Lethality correlated with severe myocardial dysfunction and fulminant heart
      failure. Mechanistically, cardiac pathology was attributed to mCa2+ overload
      driving increased generation of superoxide and necrotic cell death, which was
      rescued by genetic inhibition of mitochondrial permeability transition pore
      activation. Corroborating these findings, overexpression of NCLX in the mouse
      heart by conditional transgenesis had the beneficial effect of augmenting mCa2+
      clearance, preventing permeability transition and protecting against ischaemia
      induced cardiomyocyte necrosis and heart failure. These results demonstrate the
      essential nature of mCa2+ efflux in cellular function and suggest that augmenting
      mCa2+ efflux may be a viable therapeutic strategy in disease.

PMID- 28445459
TI  - The effect of illumination on the formation of metal halide perovskite films.
AB  - Optimizing the morphology of metal halide perovskite films is an important way to
      improve the performance of solar cells when these materials are used as light
      harvesters, because film homogeneity is correlated with photovoltaic performance.
      Many device architectures and processing techniques have been explored with the
      aim of achieving high-performance devices, including single-step deposition,
      sequential deposition and anti-solvent methods. Earlier studies have looked at
      the influence of reaction conditions on film quality, such as the concentration
      of the reactants and the reaction temperature. However, the precise mechanism of
      the reaction and the main factors that govern it are poorly understood. The
      consequent lack of control is the main reason for the large variability observed
      in perovskite morphology and the related solar-cell performance. Here we show
      that light has a strong influence on the rate of perovskite formation and on film
      morphology in both of the main deposition methods currently used: sequential
      deposition and the anti-solvent method. We study the reaction of a metal halide
      (lead iodide) with an organic compound (methylammonium iodide) using confocal
      laser scanning fluorescence microscopy and scanning electron microscopy. The lead
      iodide crystallizes before the intercalation of methylammonium iodide commences,
      producing the methylammonium lead iodide perovskite. We find that the formation
      of perovskite via such a sequential deposition is much accelerated by light. The
      influence of light on morphology is reflected in a doubling of solar-cell
      efficiency. Conversely, using the anti-solvent method to form methyl ammonium
      lead iodide perovskite in a single step from the same starting materials, we find
      that the best photovoltaic performance is obtained when films are produced in the
      dark. The discovery of light-activated crystallization not only identifies a
      previously unknown source of variability in opto-electronic properties, but also
      opens up new ways of tuning morphology and structuring perovskites for various
      applications.

PMID- 28445460
TI  - Polyglutamine tracts regulate beclin 1-dependent autophagy.
AB  - Nine neurodegenerative diseases are caused by expanded polyglutamine (polyQ)
      tracts in different proteins, such as huntingtin in Huntington's disease and
      ataxin 3 in spinocerebellar ataxia type 3 (SCA3). Age at onset of disease
      decreases with increasing polyglutamine length in these proteins and the normal
      length also varies. PolyQ expansions drive pathogenesis in these diseases, as
      isolated polyQ tracts are toxic, and an N-terminal huntingtin fragment comprising
      exon 1, which occurs in vivo as a result of alternative splicing, causes
      toxicity. Although such mutant proteins are prone to aggregation, toxicity is
      also associated with soluble forms of the proteins. The function of the polyQ
      tracts in many normal cytoplasmic proteins is unclear. One such protein is the
      deubiquitinating enzyme ataxin 3 (refs 7, 8), which is widely expressed in the
      brain. Here we show that the polyQ domain enables wild-type ataxin 3 to interact
      with beclin 1, a key initiator of autophagy. This interaction allows the
      deubiquitinase activity of ataxin 3 to protect beclin 1 from proteasome-mediated
      degradation and thereby enables autophagy. Starvation-induced autophagy, which is
      regulated by beclin 1, was particularly inhibited in ataxin-3-depleted human cell
      lines and mouse primary neurons, and in vivo in mice. This activity of ataxin 3
      and its polyQ-mediated interaction with beclin 1 was competed for by other
      soluble proteins with polyQ tracts in a length-dependent fashion. This
      competition resulted in impairment of starvation-induced autophagy in cells
      expressing mutant huntingtin exon 1, and this impairment was recapitulated in the
      brains of a mouse model of Huntington's disease and in cells from patients. A
      similar phenomenon was also seen with other polyQ disease proteins, including
      mutant ataxin 3 itself. Our data thus describe a specific function for a wild
      type polyQ tract that is abrogated by a competing longer polyQ mutation in a
      disease protein, and identify a deleterious function of such mutations distinct
      from their propensity to aggregate.

PMID- 28445461
TI  - Tumour ischaemia by interferon-gamma resembles physiological blood vessel
      regression.
AB  - The relative contribution of the effector molecules produced by T cells to tumour
      rejection is unclear, but interferon-gamma (IFNgamma) is critical in most of the
      analysed models. Although IFNgamma can impede tumour growth by acting directly on
      cancer cells, it must also act on the tumour stroma for effective rejection of
      large, established tumours. However, which stroma cells respond to IFNgamma and
      by which mechanism IFNgamma contributes to tumour rejection through stromal
      targeting have remained unknown. Here we use a model of IFNgamma induction and an
      IFNgamma-GFP fusion protein in large, vascularized tumours growing in mice that
      express the IFNgamma receptor exclusively in defined cell types. Responsiveness
      to IFNgamma by myeloid cells and other haematopoietic cells, including T cells or
      fibroblasts, was not sufficient for IFNgamma-induced tumour regression, whereas
      responsiveness of endothelial cells to IFNgamma was necessary and sufficient.
      Intravital microscopy revealed IFNgamma-induced regression of the tumour
      vasculature, resulting in arrest of blood flow and subsequent collapse of
      tumours, similar to non-haemorrhagic necrosis in ischaemia and unlike
      haemorrhagic necrosis induced by tumour necrosis factor. The early events of
      IFNgamma-induced tumour ischaemia resemble non-apoptotic blood vessel regression
      during development, wound healing or IFNgamma-mediated, pregnancy-induced
      remodelling of uterine arteries. A better mechanistic understanding of how solid
      tumours are rejected may aid the design of more effective protocols for adoptive
      T-cell therapy.

PMID- 28445463
TI  - Stem cells: Subclone wars.

PMID- 28445462
TI  - Cell diversity and network dynamics in photosensitive human brain organoids.
AB  - In vitro models of the developing brain such as three-dimensional brain organoids
      offer an unprecedented opportunity to study aspects of human brain development
      and disease. However, the cells generated within organoids and the extent to
      which they recapitulate the regional complexity, cellular diversity and circuit
      functionality of the brain remain undefined. Here we analyse gene expression in
      over 80,000 individual cells isolated from 31 human brain organoids. We find that
      organoids can generate a broad diversity of cells, which are related to
      endogenous classes, including cells from the cerebral cortex and the retina.
      Organoids could be developed over extended periods (more than 9 months), allowing
      for the establishment of relatively mature features, including the formation of
      dendritic spines and spontaneously active neuronal networks. Finally, neuronal
      activity within organoids could be controlled using light stimulation of
      photosensitive cells, which may offer a way to probe the functionality of human
      neuronal circuits using physiological sensory stimuli.

PMID- 28445464
TI  - Burgess Shale fossils illustrate the origin of the mandibulate body plan.
AB  - Retracing the evolutionary history of arthropods has been one of the greatest
      challenges in biology. During the past decade, phylogenetic analyses of
      morphological and molecular data have coalesced towards the conclusion that
      Mandibulata, the most diverse and abundant group of animals, is a distinct clade
      from Chelicerata, in that its members possess post-oral head appendages
      specialized for food processing, notably the mandible. The origin of the
      mandibulate body plan, however, which encompasses myriapods, crustaceans and
      hexapods, has remained poorly documented. Here we show that Tokummia katalepsis
      gen. et sp. nov., a large bivalved arthropod from the 508 million-year-old Marble
      Canyon fossil deposit (Burgess Shale, British Columbia), has unequivocal
      mandibulate synapomorphies, including mandibles and maxillipeds, as well as
      characters typically found in crustaceans, such as enditic, subdivided basipods
      and ring-shaped trunk segments. Tokummia and its closest relative, Branchiocaris
      (in Protocarididae, emended), also have an anteriormost structure housing a
      probable bilobed organ, which could support the appendicular origin of the
      labrum. Protocaridids are retrieved with Canadaspis and Odaraia (in Hymenocarina,
      emended) as part of an expanded mandibulate clade, refuting the idea that these
      problematic bivalved taxa, as well as other related forms, are representatives of
      the basalmost euarthropods. Hymenocarines now illustrate that the subdivision of
      the basipod and the presence of proximal endites are likely to have been
      ancestral conditions critical for the evolution of coxal and pre-coxal features
      in mandibulates. The presence of crustaceomorph traits in the Cambrian larvae of
      various clades basal to Mandibulata is reinterpreted as evidence for the
      existence of distinct ontogenetic niches among stem arthropods. Larvae would
      therefore have constituted an important source of morphological novelty during
      the Cambrian period, and, through heterochronic processes, may have contributed
      to the rapid acquisition of crown-group characters and thus to greater
      evolutionary rates during the early radiation of euarthropods.

PMID- 28445465
TI  - Assembly of functionally integrated human forebrain spheroids.
AB  - The development of the nervous system involves a coordinated succession of events
      including the migration of GABAergic (gamma-aminobutyric-acid-releasing) neurons
      from ventral to dorsal forebrain and their integration into cortical circuits.
      However, these interregional interactions have not yet been modelled with human
      cells. Here we generate three-dimensional spheroids from human pluripotent stem
      cells that resemble either the dorsal or ventral forebrain and contain cortical
      glutamatergic or GABAergic neurons. These subdomain-specific forebrain spheroids
      can be assembled in vitro to recapitulate the saltatory migration of interneurons
      observed in the fetal forebrain. Using this system, we find that in Timothy
      syndrome-a neurodevelopmental disorder that is caused by mutations in the CaV1.2
      calcium channel-interneurons display abnormal migratory saltations. We also show
      that after migration, interneurons functionally integrate with glutamatergic
      neurons to form a microphysiological system. We anticipate that this approach
      will be useful for studying neural development and disease, and for deriving
      spheroids that resemble other brain regions to assemble circuits in vitro.

PMID- 28445467
TI  - Molecular biology: The long and short of a DNA-damage response.

PMID- 28445466
TI  - Human pluripotent stem cells recurrently acquire and expand dominant negative P53
      mutations.
AB  - Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them
      an attractive source for regenerative therapies. This expansion potential has
      been linked with the acquisition of large copy number variants that provide
      mutated cells with a growth advantage in culture. The nature, extent and
      functional effects of other acquired genome sequence mutations in cultured hPS
      cells are not known. Here we sequence the protein-coding genes (exomes) of 140
      independent human embryonic stem cell (hES cell) lines, including 26 lines
      prepared for potential clinical use. We then apply computational strategies for
      identifying mutations present in a subset of cells in each hES cell line.
      Although such mosaic mutations were generally rare, we identified five unrelated
      hES cell lines that carried six mutations in the TP53 gene that encodes the
      tumour suppressor P53. The TP53 mutations we observed are dominant negative and
      are the mutations most commonly seen in human cancers. We found that the TP53
      mutant allelic fraction increased with passage number under standard culture
      conditions, suggesting that the P53 mutations confer selective advantage. We then
      mined published RNA sequencing data from 117 hPS cell lines, and observed another
      nine TP53 mutations, all resulting in coding changes in the DNA-binding domain of
      P53. In three lines, the allelic fraction exceeded 50%, suggesting additional
      selective advantage resulting from the loss of heterozygosity at the TP53 locus.
      As the acquisition and expansion of cancer-associated mutations in hPS cells may
      go unnoticed during most applications, we suggest that careful genetic
      characterization of hPS cells and their differentiated derivatives be carried out
      before clinical use.

PMID- 28445468
TI  - Discovery of intrinsic ferromagnetism in two-dimensional van der Waals crystals.
AB  - The realization of long-range ferromagnetic order in two-dimensional van der
      Waals crystals, combined with their rich electronic and optical properties, could
      lead to new magnetic, magnetoelectric and magneto-optic applications. In two
      dimensional systems, the long-range magnetic order is strongly suppressed by
      thermal fluctuations, according to the Mermin-Wagner theorem; however, these
      thermal fluctuations can be counteracted by magnetic anisotropy. Previous
      efforts, based on defect and composition engineering, or the proximity effect,
      introduced magnetic responses only locally or extrinsically. Here we report
      intrinsic long-range ferromagnetic order in pristine Cr2Ge2Te6 atomic layers, as
      revealed by scanning magneto-optic Kerr microscopy. In this magnetically soft,
      two-dimensional van der Waals ferromagnet, we achieve unprecedented control of
      the transition temperature (between ferromagnetic and paramagnetic states) using
      very small fields (smaller than 0.3 tesla). This result is in contrast to the
      insensitivity of the transition temperature to magnetic fields in the three
      dimensional regime. We found that the small applied field leads to an effective
      anisotropy that is much greater than the near-zero magnetocrystalline anisotropy,
      opening up a large spin-wave excitation gap. We explain the observed phenomenon
      using renormalized spin-wave theory and conclude that the unusual field
      dependence of the transition temperature is a hallmark of soft, two-dimensional
      ferromagnetic van der Waals crystals. Cr2Ge2Te6 is a nearly ideal two-dimensional
      Heisenberg ferromagnet and so will be useful for studying fundamental spin
      behaviours, opening the door to exploring new applications such as ultra-compact
      spintronics.

PMID- 28445470
TI  - The credibility crisis in research: Can economics tools help?
AB  - The issue of nonreplicable evidence has attracted considerable attention across
      biomedical and other sciences. This concern is accompanied by an increasing
      interest in reforming research incentives and practices. How to optimally perform
      these reforms is a scientific problem in itself, and economics has several
      scientific methods that can help evaluate research reforms. Here, we review these
      methods and show their potential. Prominent among them are mathematical modeling
      and laboratory experiments that constitute affordable ways to approximate the
      effects of policies with wide-ranging implications.

PMID- 28445471
TI  - A randomized trial comparing concise and standard consent forms in the START
      trial.
AB  - BACKGROUND: Improving the effectiveness and efficiency of research informed
      consent is a high priority. Some express concern about longer, more complex,
      written consent forms creating barriers to participant understanding. A recent
      meta-analysis concluded that randomized comparisons were needed. METHODS: We
      conducted a cluster-randomized non-inferiority comparison of a standard versus
      concise consent form within a multinational trial studying the timing of starting
      antiretroviral therapy in HIV+ adults (START). Interested sites were randomized
      to standard or concise consent forms for all individuals signing START consent.
      Participants completed a survey measuring comprehension of study information and
      satisfaction with the consent process. Site personnel reported usual site consent
      practices. The primary outcome was comprehension of the purpose of randomization
      (pre-specified 7.5% non-inferiority margin). RESULTS: 77 sites (2429
      participants) were randomly allocated to use standard consent and 77 sites (2000
      participants) concise consent, for an evaluable cohort of 4229. Site and
      participant characteristics were similar for the two groups. The concise consent
      was non-inferior to the standard consent on comprehension of randomization (80.2%
      versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two
      groups did not differ significantly on total comprehension score, satisfaction,
      or voluntariness (p>0.1). Certain independent factors, such as education,
      influenced comprehension and satisfaction but not differences between consent
      groups. CONCLUSIONS: An easier to read, more concise consent form neither
      hindered nor improved comprehension of study information nor satisfaction with
      the consent process among a large number of participants. This supports continued
      efforts to make consent forms more efficient. TRIAL REGISTRATION: Informed
      consent substudy was registered as part of START study in clinicaltrials.gov
      #NCT00867048, and EudraCT # 2008-006439-12.

PMID- 28445473
TI  - How to plan reintroductions of long-lived birds.
AB  - Reintroductions have been increasingly used for species restoration and it seems
      that this conservation tool is going to be more used in the future. Nevertheless,
      there is not a clear consensus about the better procedure for that, consequently
      a better knowledge of how to optimize this kind of management is needed. Here we
      examined the dynamics of released long-lived bird populations (lesser kestrel,
      Falco naumanni, Bonelli's eagle Aquila fasciata, and bearded vulture Gypaetus
      barbatus) in object-oriented simulated reintroduction programs. To do that,
      number of young per year and number of years of released necessary to achieve a
      successful reintroduced population were calculated. We define a successful
      reintroduction as one in which when the probability of extinction during two
      times the maximum live-span period for the species (20, 50, and 64 years
      respectively) was less than 0.001 (P<0.001) and they showed a positive trend in
      population size (r>0.00). Results showed that a similar total number of young
      (mean 98.33+/-5.26) must be released in all the species in all the scenarios in
      order to get a successful reintroduction. Consequently, as more young per year
      are released the new population is going to be larger at the end of the
      simulations, the lesser the negative effects in the donor population and the
      lowest the total budget needed will be.

PMID- 28445472
TI  - Unsuspected osteochondroma-like outgrowths in the cranial base of Hereditary
      Multiple Exostoses patients and modeling and treatment with a BMP antagonist in
      mice.
AB  - Hereditary Multiple Exostoses (HME) is a rare pediatric disorder caused by loss
      of-function mutations in the genes encoding the heparan sulfate (HS)-synthesizing
      enzymes EXT1 or EXT2. HME is characterized by formation of cartilaginous
      outgrowths-called osteochondromas- next to the growth plates of many axial and
      appendicular skeletal elements. Surprisingly, it is not known whether such tumors
      also form in endochondral elements of the craniofacial skeleton. Here, we carried
      out a retrospective analysis of cervical spine MRI and CT scans from 50
      consecutive HME patients that included cranial skeletal images. Interestingly,
      nearly half of the patients displayed moderate defects or osteochondroma-like
      outgrowths in the cranial base and specifically in the clivus. In good
      correlation, osteochondromas developed in the cranial base of mutant Ext1f/f;Col2
      CreER or Ext1f/f;Aggrecan-CreER mouse models of HME along the synchondrosis
      growth plates. Osteochondroma formation was preceded by phenotypic alteration of
      cells at the chondro-perichondrial boundary and was accompanied by ectopic
      expression of major cartilage matrix genes -collagen 2 and collagen X- within the
      growing ectopic masses. Because chondrogenesis requires bone morphogenetic
      protein (BMP) signaling, we asked whether osteochondroma formation could be
      blocked by a BMP signaling antagonist. Systemic administration with LDN-193189
      effectively inhibited osteochondroma growth in conditional Ext1-mutant mice. In
      vitro studies with mouse embryo chondrogenic cells clarified the mechanisms of
      LDN-193189 action that turned out to include decreases in canonical BMP signaling
      pSMAD1/5/8 effectors but interestingly, concurrent increases in such anti
      chondrogenic mechanisms as pERK1/2 and Chordin, Fgf9 and Fgf18 expression. Our
      study is the first to reveal that the cranial base can be affected in patients
      with HME and that osteochondroma formation is amenable to therapeutic drug
      intervention.

PMID- 28445474
TI  - Cost-effectiveness of a transitional pharmaceutical care program for patients
      discharged from the hospital.
AB  - BACKGROUND: To improve continuity of care at hospital admission and discharge and
      to decrease medication errors pharmaceutical care programs are developed. This
      study aims to determine the cost-effectiveness of the COACH program in comparison
      with usual care from a societal perspective. METHODS: A controlled clinical trial
      was performed at the Internal Medicine department of a general teaching hospital.
      All admitted patients using at least one prescription drug were included. The
      COACH program consisted of medication reconciliation, patient counselling at
      discharge, and communication to healthcare providers in primary care. The primary
      outcome was the proportion of patients with an unplanned rehospitalisation within
      three months after discharge. Also, the number of quality-adjusted life-years
      (QALYs) was assessed. Cost data were collected using cost diaries. Uncertainty
      surrounding cost differences and incremental cost-effectiveness ratios between
      the groups was estimated by bootstrapping. RESULTS: In the COACH program, 168
      patients were included and in usual care 151 patients. There was no significant
      difference in the proportion of patients with unplanned rehospitalisations (mean
      difference 0.17%, 95% CI -8.85;8.51), and in QALYs (mean difference -0.0085, 95%
      CI -0.0170;0.0001). Total costs for the COACH program were non-significantly
      lower than usual care (-?1160, 95% CI -3168;847). Cost-effectiveness planes
      showed that the program was not cost-effective compared with usual care for
      unplanned rehospitalisations and QALYs gained. CONCLUSION: The COACH program was
      not cost-effective in comparison with usual care. Future studies should focus on
      high risk patients and include other outcomes (e.g. adverse drug events) as this
      may increase the chances of a cost-effective intervention. Dutch trial register
      NTR1519.

PMID- 28445476
TI  - Social influence and political mobilization: Further evidence from a randomized
      experiment in the 2012 U.S. presidential election.
AB  - A large-scale experiment during the 2010 U.S. Congressional Election demonstrated
      a positive effect of an online get-out-the-vote message on real world voting
      behavior. Here, we report results from a replication of the experiment conducted
      during the U.S. Presidential Election in 2012. In spite of the fact that get-out
      the-vote messages typically yield smaller effects during high-stakes elections
      due to saturation of mobilization efforts from many sources, a significant
      increase in voting was again observed. Voting also increased significantly among
      the close friends of those who received the message to go to the polls, and the
      total effect on the friends was likely larger than the direct effect, suggesting
      that understanding social influence effects is potentially even more important
      than understanding the direct effects of messaging. These results replicate
      earlier work and they add to growing evidence that online social networks can be
      instrumental for spreading offline behaviors.

PMID- 28445475
TI  - GRHL3 binding and enhancers rearrange as epidermal keratinocytes transition
      between functional states.
AB  - Transcription factor binding, chromatin modifications and large scale chromatin
      re-organization underlie progressive, irreversible cell lineage commitments and
      differentiation. We know little, however, about chromatin changes as cells enter
      transient, reversible states such as migration. Here we demonstrate that when
      human progenitor keratinocytes either differentiate or migrate they form
      complements of typical enhancers and super-enhancers that are unique for each
      state. Unique super-enhancers for each cellular state link to gene expression
      that confers functions associated with the respective cell state. These super
      enhancers are also enriched for skin disease sequence variants. GRHL3, a
      transcription factor that promotes both differentiation and migration, binds
      preferentially to super-enhancers in differentiating keratinocytes, while during
      migration, it binds preferentially to promoters along with REST, repressing the
      expression of migration inhibitors. Key epidermal differentiation transcription
      factor genes, including GRHL3, are located within super-enhancers, and many of
      these transcription factors in turn bind to and regulate super-enhancers.
      Furthermore, GRHL3 represses the formation of a number of progenitor and non
      keratinocyte super-enhancers in differentiating keratinocytes. Hence, chromatin
      relocates GRHL3 binding and enhancers to regulate both the irreversible
      commitment of progenitor keratinocytes to differentiation and their reversible
      transition to migration.

PMID- 28445469
TI  - Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.
AB  - The early detection of relapse following primary surgery for non-small-cell lung
      cancer and the characterization of emerging subclones, which seed metastatic
      sites, might offer new therapeutic approaches for limiting tumour recurrence. The
      ability to track the evolutionary dynamics of early-stage lung cancer non
      invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here
      we use a tumour-specific phylogenetic approach to profile the ctDNA of the first
      100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx))
      study participants, including one patient who was also recruited to the PEACE
      (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We
      identify independent predictors of ctDNA release and analyse the tumour-volume
      detection limit. Through blinded profiling of postoperative plasma, we observe
      evidence of adjuvant chemotherapy resistance and identify patients who are very
      likely to experience recurrence of their lung cancer. Finally, we show that
      phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse
      and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

PMID- 28445477
TI  - Mitochondrial respiration in highly aerobic canines in the non-raced state and
      after a 1600-km sled dog race.
AB  - At the annual Iditarod Race, Alaskan Huskies repeatedly run for up to 8 hours at
      16 km/h to complete 1600 km. We previously demonstrated high rates of
      mitochondrial protein synthesis in Alaskan Huskies, which we suspected allowed
      rapid remodeling of mitochondrial proteins in response to energetic stress. The
      purpose of this study was to examine mitochondrial respiration in permeabilized
      skeletal muscle fibers of Alaskan Huskies in the offseason (Non-raced) and
      following the 1600 km Iditarod Sled Dog Race (Raced). We hypothesized that
      compared to Non-raced Huskies, raced Huskies that completed a 1600 km race would
      have greater mitochondrial respiratory capacities, and improvements in capacities
      of oxidative phosphorylation (OXPHOS) based on NADH-generating substrates as
      compared to fatty acids. Using high-resolution respirometry (HRR) we investigated
      the respiration of permeabilized muscle fibers from Alaskan Huskies. Maximum
      capacities were 254+/-26 pmol.s-1.mg-1 for OXPHOS (coupled, P) and 254+/-37
      pmol.s-1.mg-1 for the electron transfer system (ETS; non-coupled, E). After
      racing respiratory capacities from NADH-linked substrates, but not fat-derived
      substrates increased. Finally, the OXPHOS to ETS capacity ratio (P/E) increased
      after racing from 0.90+/-0.03 to 0.97+/-0.02. From our previous studies and the
      current study, we conclude that Alaskan Huskies maintain high mitochondrial
      protein turnover to facilitate rapid adaptation to environmental extremes and
      energetic challenges.

PMID- 28445478
TI  - Delayed histochemical alterations within the neurovascular unit due to transient
      focal cerebral ischemia and experimental treatment with neurotrophic factors.
AB  - Current stroke therapy is focused on recanalizing strategies, but neuroprotective
      co-treatments are still lacking. Modern concepts of the ischemia-affected
      neurovascular unit (NVU) and surrounding penumbra emphasize the complexity during
      the transition from initial damaging to regenerative processes. While early
      treatment with neurotrophic factors was shown to result in lesion size reduction
      and blood-brain barrier (BBB) stabilization, cellular consequences from these
      treatments are poorly understood. This study explored delayed cellular responses
      not only to ischemic stroke, but also to an early treatment with neurotrophic
      factors. Rats underwent 60 minutes of focal cerebral ischemia. Fluorescence
      labeling was applied to sections from brains perfused 7 days after ischemia.
      Analyses focused on NVU constituents including the vasculature, astrocytes and
      microglia in the ischemic striatum, the border zone and the contralateral
      hemisphere. In addition to histochemical signs of BBB breakdown, a strong up
      regulation of collagen IV and microglia activation occurred within the ischemic
      core with simultaneous degradation of astrocytes and their endfeet. Activated
      astroglia were mainly depicted at the border zone in terms of a glial scar
      formation. Early treatment with pigment epithelium-derived factor (PEDF) resulted
      in an attenuation of the usually up-regulated collagen IV-immunoreactivity.
      However, glial activation was not influenced by treatment with PEDF or the
      epidermal growth factor (EGF). In conclusion, these data on ischemia-induced
      cellular reactions within the NVU might help to develop treatments addressing the
      transition from injury towards regeneration. Thereby, the integrity of the
      vasculature in close relation to neighboring structures like astrocytes appears
      as a promising target.

PMID- 28445480
TI  - Google Earth elevation data extraction and accuracy assessment for transportation
      applications.
AB  - Roadway elevation data is critical for a variety of transportation analyses.
      However, it has been challenging to obtain such data and most roadway GIS
      databases do not have them. This paper intends to address this need by proposing
      a method to extract roadway elevation data from Google Earth (GE) for
      transportation applications. A comprehensive accuracy assessment of the GE
      extracted elevation data is conducted for the area of conterminous USA. The GE
      elevation data was compared with the ground truth data from nationwide GPS
      benchmarks and roadway monuments from six states in the conterminous USA. This
      study also compares the GE elevation data with the elevation raster data from the
      U.S. Geological Survey National Elevation Dataset (USGS NED), which is a widely
      used data source for extracting roadway elevation. Mean absolute error (MAE) and
      root mean squared error (RMSE) are used to assess the accuracy and the test
      results show MAE, RMSE and standard deviation of GE roadway elevation error are
      1.32 meters, 2.27 meters and 2.27 meters, respectively. Finally, the proposed
      extraction method was implemented and validated for the following three
      scenarios: (1) extracting roadway elevation differentiating by directions, (2)
      multi-layered roadway recognition in freeway segment and (3) slope segmentation
      and grade calculation in freeway segment. The methodology validation results
      indicate that the proposed extraction method can locate the extracting route
      accurately, recognize multi-layered roadway section, and segment the extracted
      route by grade automatically. Overall, it is found that the high accuracy
      elevation data available from GE provide a reliable data source for various
      transportation applications.

PMID- 28445479
TI  - In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD
      L1) rat-bovine chimeric antibody against bovine leukemia virus infection.
AB  - Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to
      be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many
      chronic diseases. We previously found that PD-L1 expression was upregulated in
      cattle infected with bovine leukemia virus (BLV) and that an antibody that
      blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro.
      Therefore, this study assessed its antivirus activities in vivo. First, we
      inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected
      cow. However, this did not induce T-cell proliferation or reduction of BLV
      provirus loads during the test period, and only bound to circulating IgM+ B cells
      until one week post-inoculation. We hypothesized that this lack of in vivo
      effects was due to its lower stability in cattle and so established an anti-PD-L1
      rat-bovine chimeric antibody (Boch4G12). Boch4G12 was able to bind specifically
      with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune
      response in both healthy and BLV-infected cattle in vitro. Therefore, we
      experimentally infected a healthy calf with BLV and inoculated it intravenously
      with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL) stage. Cultivation of
      peripheral blood mononuclear cells (PBMCs) isolated from the tested calf
      indicated that the proliferation of CD4+ T cells was increased by Boch4G12
      inoculation, while BLV provirus loads were significantly reduced, clearly
      demonstrating that this treatment induced antivirus activities. Therefore,
      further studies using a large number of animals are required to support its
      efficacy for clinical application.

PMID- 28445482
TI  - Questionable science and reproducibility in electrical brain stimulation
      research.
AB  - Electrical brain stimulation (EBS) is a trendy new technique used to change brain
      function and treat neurological, psychiatric and psychological disorders. We were
      curious whether the published literature, which is dominated by positive results,
      reflects the experience of researchers using EBS. Specifically, we wanted to know
      whether researchers are able to reproduce published EBS effects and whether they
      engage in, but fail to report, questionable research practices. We invited 976
      researchers to complete an online survey. We also audited 100 randomly-selected
      published EBS papers. A total of 154 researchers completed the survey. Survey
      respondents had a median of 3 [1 to 6, IQR] published EBS papers (1180 total) and
      2 [1 to 3] unpublished ones (380 total). With anodal and cathodal EBS, the two
      most widely used techniques, 45-50% of researchers reported being able to
      routinely reproduce published results. When asked about how study sample size was
      determined, 69% of respondents reported using the sample size of published
      studies, while 61% had used power calculations, and 32% had based their decision
      on pilot data. In contrast, our audit found only 6 papers where power
      calculations were used and a single paper in which pilot data was used. When
      asked about questionable research practices, survey respondents were aware of
      other researchers who selectively reported study outcomes (41%) and experimental
      conditions (36%), adjusted statistical analysis to optimise results (43%), and
      engaged in other shady practices (20%). Fewer respondents admitted to engaging in
      these practices themselves, although 25% admitted to adjusting statistical
      analysis to optimize results. There was strong agreement that such practices
      should be reported in research papers; however, our audit found only two such
      admissions. The present survey confirms that questionable research practices and
      poor reproducibility are present in EBS studies. The belief that EBS is effective
      needs to be replaced by a more rigorous approach so that reproducible brain
      stimulation methods can be devised and applied.

PMID- 28445481
TI  - Hypomethylating agents synergize with irinotecan to improve response to
      chemotherapy in colorectal cancer cells.
AB  - Colorectal cancer (CRC) is the second leading cause of cancer death in the United
      States. In the metastatic setting, the majority of patients respond to initial
      therapies but eventually develop resistance and progress. In this study, we test
      the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines,
      which were previously resistant to subsequent chemotherapeutic agents. When
      multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating
      agent, 5-aza-cytidine (AZA) in-vitro, and the cells then established as in-vivo
      xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic
      chemotherapy with agents commonly used in CRC treatment. For irinotecan (IRI),
      growth diminished by 16-62 fold as assessed, by both proliferation (IC50) and
      anchorage independent cell growth soft agar assays. Treatment of resistant HCT116
      cell line along with in-vivo, for CRC line xenografts, AZA plus IRI again
      exhibits this synergistic response with significant improvement in survival and
      tumor regression in the mice. Genome-wide expression correlates changes in
      pathways for cell adhesion and DNA repair with the above responses. A Phase 1/2
      clinical trial testing this concept is already underway testing the clinical
      efficacy of this concept in IRI resistant, metastatic CRC (NCT01896856).

PMID- 28445483
TI  - Community barcoding reveals little effect of ocean acidification on the
      composition of coastal plankton communities: Evidence from a long-term mesocosm
      study in the Gullmar Fjord, Skagerrak.
AB  - The acidification of the oceans could potentially alter marine plankton
      communities with consequences for ecosystem functioning. While several studies
      have investigated effects of ocean acidification on communities using traditional
      methods, few have used genetic analyses. Here, we use community barcoding to
      assess the impact of ocean acidification on the composition of a coastal plankton
      community in a large scale, in situ, long-term mesocosm experiment. High
      throughput sequencing resulted in the identification of a wide range of
      planktonic taxa (Alveolata, Cryptophyta, Haptophyceae, Fungi, Metazoa, Hydrozoa,
      Rhizaria, Straminipila, Chlorophyta). Analyses based on predicted operational
      taxonomical units as well as taxonomical compositions revealed no differences
      between communities in high CO2 mesocosms (~ 760 MUatm) and those exposed to
      present-day CO2 conditions. Observed shifts in the planktonic community
      composition were mainly related to seasonal changes in temperature and nutrients.
      Furthermore, based on our investigations, the elevated CO2 did not affect the
      intraspecific diversity of the most common mesozooplankter, the calanoid copepod
      Pseudocalanus acuspes. Nevertheless, accompanying studies found temporary effects
      attributed to a raise in CO2. Differences in taxa composition between the CO2
      treatments could, however, only be observed in a specific period of the
      experiment. Based on our genetic investigations, no compositional long-term
      shifts of the plankton communities exposed to elevated CO2 conditions were
      observed. Thus, we conclude that the compositions of planktonic communities,
      especially those in coastal areas, remain rather unaffected by increased CO2.

PMID- 28445485
TI  - Validity and reliability of the Physical Activity Questionnaire for Children (PAQ
      C) and Adolescents (PAQ-A) in individuals with congenital heart disease.
AB  - OBJECTIVE: To assess the criterion validity, internal consistency, reliability
      and cut-point for the Physical Activity Questionnaire for Children (PAQ-C) and
      Adolescents (PAQ-A) in children and adolescents with congenital heart disease-a
      special population at high cardiovascular risk in whom physical activity has not
      been extensively evaluated. METHODS: We included 84 participants (13.6+/-2.9 yrs,
      50% female) with simple (37%), moderate (31%), or severe congenital heart disease
      (27%), as well as cardiac transplant recipients (6%), from BC Children's
      Hospital, Canada. They completed the PAQ-C (<=11yrs, n = 28) or-A (>=12yrs, n =
      56), and also wore a triaxial accelerometer (GT3X+ or GT9X) over the right hip
      for 7 days (n = 59 met valid wear time criteria). RESULTS: Median daily moderate
      to-vigorous physical activity was 46.9 minutes per day (IQR 31.6-61.8) and 25%
      met physical activity guidelines defined as >=60 minutes of moderate-to-vigorous
      physical activity per day. Median PAQ-score was 2.6 (IQR 1.9-3.0). PAQ-Scores
      were significantly related to accelerometry-derived metrics of physical activity
      (rho = 0.44-0.55, all p<0.01) and sedentary behaviour (rho = -0.53, p<0.001).
      Internal consistency was high (alpha = 0.837), as was reliability (stability) of
      PAQ-Scores over a 4-months period (ICC = 0.73, 95%CI 0.55-0.84; p<0.001). We
      identified that a PAQ-Score cut-point of 2.87 discriminates between those meeting
      physical guidelines and those that do not in the combined PAQ-C and-A samples
      (area under the curve = 0.80 (95%CI 0.67-0.92). CONCLUSION: Validity and
      reliability of the PAQ in children and adolescents with CHD was comparable to or
      stronger than previous studies in healthy children. Therefore, the PAQ may be
      used to estimate general levels of physical activity in children and adolescents
      with CHD.

PMID- 28445484
TI  - Transcriptome analysis of creeping bentgrass exposed to drought stress and
      polyamine treatment.
AB  - Creeping bentgrass is an important cool-season turfgrass species sensitive to
      drought. Treatment with polyamines (PAs) has been shown to improve drought
      tolerance; however, the mechanism is not yet fully understood. Therefore, this
      study aimed to evaluate transcriptome changes of creeping bentgrass in response
      to drought and exogenous spermidine (Spd) application using RNA sequencing (RNA
      Seq). The high-quality sequences were assembled and 18,682 out of 49,190 (38%)
      were detected as coding sequences. A total of 22% and 19% of genes were found to
      be either up- or down-regulated due to drought while 20% and 34% genes were
      either up- or down- regulated in response to Spd application under drought
      conditions, respectively. Gene ontology (GO) and enrichment analysis were used to
      interpret the biological processes of transcripts and relative transcript
      abundance. Enriched or differentially expressed transcripts due to drought stress
      and/or Spd application were primarily associated with energy metabolism,
      transport, antioxidants, photosynthesis, signaling, stress defense, and cellular
      response to water deprivation. This research is the first to provide
      transcriptome data for creeping bentgrass under an abiotic stress using RNA-Seq
      analysis. Differentially expressed transcripts identified here could be further
      investigated for use as molecular markers or for functional analysis in responses
      to drought and Spd.

PMID- 28445486
TI  - A metamodel for mobile forensics investigation domain.
AB  - With the rapid development of technology, mobile phones have become an essential
      tool in terms of crime fighting and criminal investigation. However, many mobile
      forensics investigators face difficulties with the investigation process in their
      domain. These difficulties are due to the heavy reliance of the forensics field
      on knowledge which, although a valuable resource, is scattered and widely
      dispersed. The wide dispersion of mobile forensics knowledge not only makes
      investigation difficult for new investigators, resulting in substantial waste of
      time, but also leads to ambiguity in the concepts and terminologies of the mobile
      forensics domain. This paper developed an approach for mobile forensics domain
      based on metamodeling. The developed approach contributes to identify common
      concepts of mobile forensics through a development of the Mobile Forensics
      Metamodel (MFM). In addion, it contributes to simplifying the investigation
      process and enables investigation teams to capture and reuse specialized forensic
      knowledge, thereby supporting the training and knowledge management activities.
      Furthermore, it reduces the difficulty and ambiguity in the mobile forensics
      domain. A validation process was performed to ensure the completeness and
      correctness of the MFM. The validation was conducted using two techniques for
      improvements and adjustments to the metamodel. The last version of the adjusted
      metamodel was named MFM 1.2.

PMID- 28445487
TI  - BMT decreases HFD-induced weight gain associated with decreased preadipocyte
      number and insulin secretion.
AB  - Experimental bone marrow transplantation (BMT) in mice is commonly used to assess
      the role of immune cell-specific genes in various pathophysiological settings.
      The application of BMT in obesity research is hampered by the significant
      reduction in high-fat diet (HFD)-induced obesity. We set out to characterize
      metabolic tissues that may be affected by the BMT procedure and impair the HFD
      induced response. Male C57BL/6 mice underwent syngeneic BMT using lethal
      irradiation. After a recovery period of 8 weeks they were fed a low-fat diet
      (LFD) or HFD for 16 weeks. HFD-induced obesity was reduced in mice after BMT as
      compared to HFD-fed control mice, characterized by both a reduced fat (-33%;
      p<0.01) and lean (-11%; p<0.01) mass, while food intake and energy expenditure
      were unaffected. As compared to control mice, BMT-treated mice had a reduced
      mature adipocyte volume (approx. -45%; p<0.05) and reduced numbers of
      preadipocytes (-38%; p<0.05) and macrophages (-62%; p<0.05) in subcutaneous,
      gonadal and visceral white adipose tissue. In BMT-treated mice, pancreas weight (
      46%; p<0.01) was disproportionally decreased. This was associated with reduced
      plasma insulin (-68%; p<0.05) and C-peptide (-37%; p<0.01) levels and a delayed
      glucose clearance in BMT-treated mice on HFD as compared to control mice. In
      conclusion, the reduction in HFD-induced obesity after BMT in mice is at least
      partly due to alterations in the adipose tissue cell pool composition as well as
      to a decreased pancreatic secretion of the anabolic hormone insulin. These
      effects should be considered when interpreting results of experimental BMT in
      metabolic studies.

PMID- 28445488
TI  - A versatile method for dynamically controlled patterning of small populations of
      epithelial cells on substrates via non-contact piezoelectric inkjet printing.
AB  - Intercellular interactions play a central role at the tissue and whole organism
      level modulating key cellular functions in normal and disease states. Studies of
      cell-cell communications are challenging due to ensemble averaging effects
      brought about by intrinsic heterogeneity in cellular function which requires such
      studies to be conducted with small populations of cells. Most of the current
      methods for producing and studying such small cell populations are complex to
      implement and require skilled personnel limiting their widespread utility in
      biomedical research labs. We present a simple and rapid method to produce small
      populations with varying size of epithelial cells (10-50 cells/population) with
      high-throughput (~ 1 population/second) on flat surfaces via patterning of
      extracellular matrix (ECM) proteins and random seeding of cells. We demonstrate
      that despite inherent limitations of non-contact, drop-on-demand piezoelectric
      inkjet printing for protein patterning, varying mixtures of ECM proteins can be
      deposited with high reproducibility and level of control on glass substrates
      using a set of dynamically adjustable optimized deposition parameters. We
      demonstrate high consistency for the number of cells per population (~1 cell
      standard error of mean), the population's size (~0.2 coefficient of variation)
      and shape, as well as accurate spatial placement of and distance between colonies
      of a panel of metaplastic and dysplastic esophageal epithelial cells with
      differing adhesion and motility characteristics. The number of cells per colony,
      colony size and shape can be varied by dynamically varying the amount of ECM
      proteins deposited per spatial location and the number of spatial locations on
      the substrate. The method is applicable to a broad range of biological and
      biomedical studies including cell-cell communications, cellular microenvironment,
      migration, and stimulus response.

PMID- 28445489
TI  - Video quality assessment using motion-compensated temporal filtering and manifold
      feature similarity.
AB  - Well-performed Video quality assessment (VQA) method should be consistent with
      human visual systems for better prediction accuracy. In this paper, we propose a
      VQA method using motion-compensated temporal filtering (MCTF) and manifold
      feature similarity. To be more specific, a group of frames (GoF) is first
      decomposed into a temporal high-pass component (HPC) and a temporal low-pass
      component (LPC) by MCTF. Following this, manifold feature learning (MFL) and
      phase congruency (PC) are used to predict the quality of temporal LPC and
      temporal HPC respectively. The quality measures of the LPC and the HPC are then
      combined as GoF quality. A temporal pooling strategy is subsequently used to
      integrate GoF qualities into an overall video quality. The proposed VQA method
      appropriately processes temporal information in video by MCTF and temporal
      pooling strategy, and simulate human visual perception by MFL. Experiments on
      publicly available video quality database showed that in comparison with several
      state-of-the-art VQA methods, the proposed VQA method achieves better consistency
      with subjective video quality and can predict video quality more accurately.

PMID- 28445490
TI  - The effect of swimming exercise on adenine-induced kidney disease in rats, and
      the influence of curcumin or lisinopril thereon.
AB  - Patients with chronic kidney disease (CKD) have been reported to benefit from
      different types of exercises. It has also been shown that the ACE inhibitor
      lisinopril, and the natural product curcumin are also beneficial in different
      models of CKD in rats. We assessed the influence of moderate swimming exercise
      (SE) on rats with adenine-induced CKD, and tested the possible effects of
      lisinopril and/or curcumin thereon using several physiological, biochemical,
      histopathological and immunohistochemical parameters. Rats (either sedentary or
      subjected to SE) were randomly divided into several groups, and given for five
      weeks either normal food or food mixed with adenine (0.25% w/w) to induce CKD.
      Some of these groups were also concomitantly treated orally with curcumin (75
      mg/kg), or lisinopril (10 mg/kg) and were subjected to moderate SE (45 min/day
      three days each week). Rats fed adenine showed the typical biochemical,
      histopathological signs of CKD such as elevations in blood pressure, urinary
      albumin / creatinine ratio, and plasma urea, creatinine, indoxyl sulfate and
      phosphorus. SE, curcumin or lisinopril, given singly, significantly ameliorated
      all the adenine-induced actions. Administering curcumin or lisinopril with SE
      improved the histopathology of the kidneys, a salutary effect not seen with SE
      alone. Combining SE to the nephroprotective agents' curcumin or lisinopril might
      offer additional nephroprotection.

PMID- 28445491
TI  - How people used ochre at Rose Cottage Cave, South Africa: Sixty thousand years of
      evidence from the Middle Stone Age.
AB  - We describe colour, hardness, grain size, geological type and surface
      modifications of ochre pieces excavated, first by Malan and later by Harper, from
      the Middle Stone Age (MSA) of Rose Cottage Cave, 96, 000 to 30, 000 years ago.
      Soft, bright-red shales are abundant, and most ochre has clayey or silty grain
      sizes. The post-Howiesons Poort layers contain the most ochre pieces, but the
      Howiesons Poort layers have the highest frequency of ochre per sediment volume.
      The pre-Howiesons Poort layers have the highest utilization rate. Use-traces
      include rubbing, grinding, combined grinding and rubbing, and rare instances of
      scoring. The processing techniques are proxies for ochre use. Rubbing transfers
      red ochre powder directly onto soft surfaces, such as human skin, or animal hide.
      This is appropriate when skin colouring and marking or skin protection (for
      example from sun, insects or bacteria) is the purpose. Grinding produces ochre
      powder that can be used for a variety of tasks. It can be mixed with water or
      other products to create paint, cosmetics or adhesives. Multiple uses of ochre
      powder and ochre pieces are therefore implied at Rose Cottage and changes through
      time are apparent.

PMID- 28445493
TI  - Polyphyly of the extinct family Oviparosiphidae and its implications for
      inferring aphid evolution (Hemiptera, Sternorrhyncha).
AB  - Aphidoidea, the so-called "true aphids" are one of the most challenging groups in
      terms of solving the phylogenetic relationships. Morphology-based analyses were
      strongly affected by widespread homoplasy, while the molecular-based attempts
      struggled with the lack of sufficient phylogenetic signal. Despite significant
      improvements, the higher classification still remains unresolved and rather
      controversial. However, the use of the fossil record, one of the most valuable
      sources of information, was mainly limited to calibration of a phylogenetic tree,
      without a direct inclusion into the analysis. The extinct family Oviparosiphidae
      has long been considered as the common ancestor of all recent Aphidoidea and it
      was used as a calibration point in several analyses, but it has been never
      analyzed in a phylogenetic context. The family has been treated as a monophyletic
      group purely based on the simultaneous presence of two abdominal structures,
      ovipositor and siphunculi. However, it has been shown recently that at least one
      more extinct lineage, present at the same time, was characterized by the same
      features. For these reasons, we performed a maximum parsimony analysis using
      morphological data for extinct aphid taxa to prove the monophyly of
      Oviparosiphidae. Our analysis shows that the presumed ancestor lineage of recent
      aphids is a polyphyletic group. Our results support the hypothesis of an early
      Mesozoic rapid radiation of aphids, which led to several different lineages
      characterized by both ovipositor and siphunculi. The results indicate the
      necessity of examining the other extinct families, and shows that the diversity
      of aphids before the Cretaceous Terrestrial Revolution (KTR) was higher than
      expected. Even though there is not enough data to perform a formal analysis,
      fossils seem to suggest a significant impact of the KTR on aphid diversification.
      Additionally, we have made a redescription of two genera and description of a new
      species, Vitimaphis subridens sp. nov.

PMID- 28445492
TI  - Shoot stem cell specification in roots by the WUSCHEL transcription factor.
AB  - The WUSCHEL homeobox transcription factor is required to specify stem-cell
      identity at the shoot apical meristem and its ectopic expression is sufficient to
      induce de novo shoot meristem formation. Yet, the manner by which WUS promotes
      stem-cell fate is not yet fully understood. In the present research we address
      this question by inducing WUS function outside of its domain. We show that
      activation of WUS function in the root inhibits the responses to exogenous auxin
      and suppresses the initiation and growth of lateral roots. Using time lapse
      movies to follow the cell-cycle marker CYCB1;1::GFP, we also show that activation
      of WUS function suppresses cell division and cell elongation. In addition,
      activation of WUS represses the auxin-induced expression of the PLETHORA1 root
      identity gene and promotes shoot fate. Shoot apical meristem formation requires a
      high cytokinin-to-auxin ratio. Our findings provide evidence for the manner by
      which WUS specifies stem-cell identity: by affecting auxin responses, by reducing
      the cell mitotic activity and by repressing other developmental pathways. At the
      meristem, the stem-cells which are characterized by low division rate are
      surrounded by the highly proliferative meristematic cells. Our results also
      provide a model for WUS establishing the differential mitotic rates between two
      cell populations at the minute structure of the meristem.

PMID- 28445494
TI  - Maternal perception of children's nutritional status in the Federal District,
      Brazil.
AB  - Maternal perception of child's nutritional status has a potential impact on the
      identification, prevention, and treatment of childhood overweight. Thus, the aim
      of this study was to evaluate the prevalence of misperception and factors
      associated with maternal perception of the nutritional status of first- to third
      grade elementary school students from private schools in the Federal District,
      Brazil. This cross-sectional study was conducted with 554 mother-child pairs.
      Children's nutritional status was assessed by measuring their weight and height.
      The mothers completed an online questionnaire about sociodemographic data,
      maternal nutritional status, maternal perception of her own nutritional status
      (silhouette scale for female adults), and maternal perception of child's
      nutritional status (silhouette scale for children). Only 30.0% of the mothers
      were successful in choosing the most appropriate silhouette to represent child's
      nutritional status. Highly educated mothers (Adjusted OR = 1.51) and mothers of
      male children (Adjusted OR = 2.53) or of non-overweight children (Adjusted OR =
      1.65) were more likely to underestimate child's nutritional status. Conversely,
      mothers below 35 years of age (Adjusted OR = 1.85) and mothers of female children
      (Adjusted OR = 2.24) or of overweight children (Adjusted OR = 1.94) were more
      likely to overestimate child's nutritional status. There was a high prevalence of
      misperception, which shows the need for interventions for children that take into
      account the relevance of mother's role and the adequate recognition of child's
      nutritional status.

PMID- 28445495
TI  - Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and
      buccal administration of a high-concentration formulation of buprenorphine in
      conscious cats.
AB  - BACKGROUND: The aim of this study was to describe the joint pharmacokinetic
      pharmacodynamic model and evaluate thermal antinociception of a high
      concentration formulation of buprenorphine (SimbadolTM) in cats. METHODS: Six
      healthy cats (4.9 +/- 0.7 kg) were included in a prospective, randomized,
      blinded, crossover study. SimbadolTM (1.8 mg mL-1) was administered by the
      subcutaneous (SC; 0.24 mg kg-1), intravenous (IV; 0.12 mg kg-1) or buccal (OTM;
      0.12 mg kg-1) route of administration and thermal thresholds (TT) were compared
      with a saline group (SAL). Thermal threshold testing and blood sampling were
      performed at predetermined time points up to 72 hours including a placebo group.
      Plasma buprenorphine and norbuprenorphine concentrations were measured using
      liquid chromatography mass spectrometry. A bespoke bicompartmental
      pharmacokinetic model simultaneously fitted data from two analytes/three routes
      of administration. Temporal changes in TT were analyzed using one-way ANOVA
      followed by Dunnett's test and treatment comparisons using two-way ANOVA with
      Bonferroni's correction (P < 0.05). RESULTS: Thermal thresholds were
      significantly increased after SC, IV and OTM from 1-24 hours (except 2 hours),
      0.5-8 hours (except 6 hours), and 1-8 hours (except 6 hours), respectively, when
      compared with baseline. Thermal thresholds were significantly increased after SC
      (1-30 hours), IV (1-8 hours) and OTM (1-12 hours) when compared with SAL, but not
      different among buprenorphine-treated cats. The absolute buprenorphine clearance
      was 0.98 L kg-1 hour-1, volume of distribution at steady state was 7.9 L kg-1 and
      the elimination-half-life was 12.3 hours. Bioavailability for SC and OTM was 94%
      and 24%, respectively. Subcutaneous absorption was biphasic. An initial peak
      (0.08 hours) was followed by a slow (half-life 11.2 hours) and progressive (peak
      acceleration at 2.8 hours) uptake. CONCLUSION: The SC administration of
      SimbadolTM was characterized by prolonged absorption half-life and sustained
      plasma concentrations yielding long-lasting antinociception (>= 24 hours) when
      compared with the IV and OTM routes.

PMID- 28445496
TI  - A fuzzy co-clustering algorithm for biomedical data.
AB  - Fuzzy co-clustering extends co-clustering by assigning membership functions to
      both the objects and the features, and is helpful to improve clustering accurarcy
      of biomedical data. In this paper, we introduce a new fuzzy co-clustering
      algorithm based on information bottleneck named ibFCC. The ibFCC formulates an
      objective function which includes a distance function that employs information
      bottleneck theory to measure the distance between feature data point and the
      feature cluster centroid. Many experiments were conducted on five biomedical
      datasets, and the ibFCC was compared with such prominent fuzzy (co-)clustering
      algorithms as FCM, FCCM, RFCC and FCCI. Experimental results showed that ibFCC
      could yield high quality clusters and was better than all these methods in terms
      of accuracy.

PMID- 28445497
TI  - Prostaglandin E2 produced following infection with Theiler's virus promotes the
      pathogenesis of demyelinating disease.
AB  - Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV)
      activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)
      dependent pathways, resulting in the production of IL-1beta via the activation of
      caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome.
      The role of IL-1beta in the pathogenesis of TMEV-induced demyelinating disease
      was previously investigated. However, the signaling effects of prostaglandin E2
      (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral
      determinants and the pathogenesis of demyelinating disease are unknown. In this
      study, we investigated the levels of intermediate molecules leading to PGE2
      signaling and the effects of blocking PGE2 signaling on the immune response to
      TMEV infection, viral persistence and the development of demyelinating disease.
      We demonstrate here that TMEV infection activates the NLRP3 inflammasome and PGE2
      signaling much more vigorously in dendritic cells (DCs) and CD11b+ cells from
      susceptible SJL mice than in cells from resistant B6 mice. Inhibition of virus
      induced PGE2 signaling using AH23848 resulted in decreased pathogenesis of
      demyelinating disease and viral loads in the central nervous system (CNS). In
      addition, AH23848 treatment caused the elevation of protective early IFN-gamma
      producing CD4+ and CD8+ T cell responses. Because the levels of IFN-beta were
      lower in AH23848-treated mice but the level of IL-6 was similar, over-production
      of pathogenic IFN-beta was modulated and the generation of IFN-gamma-producing T
      cell responses was enhanced by the inhibition of PGE2 signaling. These results
      strongly suggest that excessive activation of the NLRP3 inflammasome and
      downstream PGE2 signaling contribute to the pathogenesis of TMEV-induced
      demyelinating disease.

PMID- 28445498
TI  - Metabolic profiles by 1H-magnetic resonance spectroscopy in natalizumab
      associated post-PML lesions of multiple sclerosis patients who survived
      progressive multifocal leukoencephalopathy (PML).
AB  - PURPOSE: Early diagnosis and treatment of multiple sclerosis-related progressive
      multifocal leukoencephalopathy (PML) significantly improve clinical outcomes.
      However, there is a lack of information regarding the restart of immunomodulatory
      therapy in the post-PML setting, when multiple sclerosis activity reappears. We
      aimed at the examination of metabolic differences using 1H-magnetic resonance
      spectroscopy (1H-MRS) in multiple sclerosis patients at various post-PML stages
      and at the exploration of differences according to their disease and JC virus
      (JCV) status. METHODS: 1H-MRS of PML lesions was carried out on 15 relapsing
      remitting multiple sclerosis patients with natalizumab-associated PML. Patients
      were grouped according to their stage after PML infection as early post-PML, less
      than 19 months after PML onset (n = 5), or late post-PML group, more than 23
      months after PML onset (n = 10). The latter group was further categorized
      according to persisting JCV load in the cerebrospinal fluid. RESULTS: Early post
      PML patients showed significantly higher Lipid/Creatine ratios within PML lesions
      than late post-PML (p = 0.036). Furthermore, N-Acetyl-Aspartate/Creatine and N
      Acetyl-Aspartate/Choline were significantly reduced in early post-PML and late
      post-PML lesions relative to normal-appearing white matter. In late post-PML,
      virus-positive patients showed significantly higher ratios of Choline/Creatine (p
      = 0.019) and consequently a reduced N-Acetyl- Aspartate/Choline ratio (p = 0.010)
      in contrast to virus-negative patients. In late post-PML patients with persisting
      viral load, an elevated Choline/Creatine ratio correlated significantly with
      higher disability. CONCLUSIONS: 1H-MRS may provide additional information related
      to underlying PML disease activity in various post-PML stages. In particular,
      Choline/Creatine levels, Lipid levels, and N-Acetyl- Aspartate/Choline are
      relevant markers in the post-PML setting, taking also the JCV status into
      account.

PMID- 28445499
TI  - Fine-scale population genetic structure of the Bengal tiger (Panthera tigris
      tigris) in a human-dominated western Terai Arc Landscape, India.
AB  - Despite massive global conservation strategies, tiger populations continued to
      decline until recently, mainly due to habitat loss, human-animal conflicts, and
      poaching. These factors are known to affect the genetic characteristics of tiger
      populations and decrease local effective population sizes. The Terai Arc
      Landscape (TAL) at the foothills of the Himalaya is one of the 42 source sites of
      tigers around the globe. Therefore, information on how landscape features and
      anthropogenic factors affect the fine-scale spatial genetic structure and
      variation of tigers in TAL is needed to develop proper management strategies for
      achieving long-term conservation goals. We document, for the first time, the
      genetic characteristics of this tiger population by genotyping 71 tiger samples
      using 13 microsatellite markers from the western region of TAL (WTAL) of 1800
      km2. Specifically, we aimed to estimate the genetic variability, population
      structure, and gene flow. The microsatellite markers indicated that the levels of
      allelic diversity (MNA = 6.6) and genetic variation (Ho = 0.50, HE = 0.64) were
      slightly lower than those reported previously in other Bengal tiger populations.
      We observed moderate gene flow and significant genetic differentiation (FST=
      0.060) and identified the presence of cryptic genetic structure using Bayesian
      and non-Bayesian approaches. There was low and significantly asymmetric migration
      between the two main subpopulations of the Rajaji Tiger Reserve and the Corbett
      Tiger Reserve in WTAL. Sibship relationships indicated that the functionality of
      the corridor between these subpopulations may be retained if the quality of the
      habitat does not deteriorate. However, we found that gene flow is not adequate in
      view of changing land use matrices. We discuss the need to maintain connectivity
      by implementing the measures that have been suggested previously to minimize the
      level of human disturbance, including relocation of villages and industries,
      prevention of encroachment, and banning sand and boulder mining in the corridors.

PMID- 28445500
TI  - SF3B1 is a stress-sensitive splicing factor that regulates both HSF1
      concentration and activity.
AB  - The heat shock response (HSR) is a well-conserved, cytoprotective stress response
      that activates the HSF1 transcription factor. During severe stress, cells inhibit
      mRNA splicing which also serves a cytoprotective function via inhibition of gene
      expression. Despite their functional interconnectedness, there have not been any
      previous reports of crosstalk between these two pathways. In a genetic screen, we
      identified SF3B1, a core component of the U2 snRNP subunit of the spliceosome, as
      a regulator of the heat shock response in Caenorhabditis elegans. Here, we show
      that this regulatory connection is conserved in cultured human cells and that
      there are at least two distinct pathways by which SF3B1 can regulate the HSR.
      First, inhibition of SF3B1 with moderate levels of Pladienolide B, a previously
      established small molecule inhibitor of SF3B1, affects the transcriptional
      activation of HSF1, the transcription factor that mediates the HSR. However, both
      higher levels of Pladienolide B and SF3B1 siRNA knockdown also change the
      concentration of HSF1, a form of HSR regulation that has not been previously
      documented during normal physiology but is observed in some forms of cancer.
      Intriguingly, mutations in SF3B1 have also been associated with several distinct
      types of cancer. Finally, we show that regulation of alternative splicing by
      SF3B1 is sensitive to temperature, providing a new mechanism by which temperature
      stress can remodel the transcriptome.

PMID- 28445501
TI  - Out-of-hospital cardiac arrest survival in drug-related versus cardiac causes in
      Ontario: A retrospective cohort study.
AB  - BACKGROUND: Drug overdose causes approximately 183,000 deaths worldwide annually
      and 50,000 deaths in Canada and the United States combined. Drug-related deaths
      are concentrated among young people, leading to a substantial burden of disease
      and loss of potential life years. Understanding the epidemiology, patterns of
      care, and prognosis of drug-related prehospital emergencies may lead to improved
      outcomes. METHODS: We conducted a retrospective cohort study of out-of-hospital
      cardiac arrests with drug-related and presumed cardiac causes between 2007 and
      2013 using the Toronto Regional RescuNet Epistry database. The primary outcome
      was survival to hospital discharge. We computed standardized case fatality rates,
      and odds ratios of survival to hospital discharge for cardiac arrests with drug
      related versus presumed cardiac causes, adjusting for confounders using logistic
      regression. RESULTS: The analysis involved 21,497 cardiac arrests, including 378
      (1.8%) drug-related and 21,119 (98.2%) presumed cardiac. Compared with the
      presumed cardiac group, drug-related arrest patients were younger and less likely
      to receive bystander resuscitation, have initial shockable cardiac rhythms, or be
      transported to hospital. There were no significant differences in emergency
      medical service response times, return of spontaneous circulation, or survival to
      discharge. Standardized case fatality rates confirmed that these effects were not
      due to age or sex differences. Adjusting for known predictors of survival, drug
      related cardiac arrest was associated with increased odds of survival to hospital
      discharge (OR1.44, 95%CI 1.15-1.81). INTERPRETATION: In out-of-hospital cardiac
      arrest, patients with drug-related causes are less likely than those with
      presumed cardiac causes to receive bystander resuscitation or have an initial
      shockable rhythm, but are more likely to survive after accounting for predictors
      of survival. The demographics and outcomes among drug-related cardiac arrest
      patients offers unique opportunities for prehospital intervention.

PMID- 28445502
TI  - Role of Kif15 and its novel mitotic partner KBP in K-fiber dynamics and
      chromosome alignment.
AB  - Faithful segregation of the genetic material during the cell cycle is key for the
      continuation of life. Central to this process is the assembly of a bipolar
      spindle that aligns the chromosomes and segregates them to the two daughter
      cells. Spindle bipolarity is strongly dependent on the activity of the
      homotetrameric kinesin Eg5. However, another kinesin, Kif15, also provides forces
      needed to separate the spindle poles during prometaphase and to maintain spindle
      bipolarity at metaphase. Here we identify KBP as a specific interaction partner
      of Kif15 in mitosis. We show that KBP promotes the localization of Kif15 to the
      spindle equator close to the chromosomes. Both Kif15 and KBP are required for the
      alignment of all the chromosomes to the metaphase plate and the assembly of
      stable kinetochore fibers of the correct length. Taken together our data uncover
      a novel role for Kif15 in complex with KBP during mitosis.

PMID- 28445504
TI  - Correction: Gastroenteritis Therapies in Developed Countries: Systematic Review
      and Meta-Analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0128754.].

PMID- 28445503
TI  - Therapeutic efficacy of artemether-lumefantrine against uncomplicated Plasmodium
      falciparum malaria in a high-transmission area in northwest Ethiopia.
AB  - Malaria, particularly due to Plasmodium falciparum, remains a major public health
      threat in Ethiopia. Artemether-lumefantine (AL) has been the first-line
      antimalarial drug against uncomplicated P. falciparum malaria in the country
      since 2004. Regular monitoring of antimalarial drugs is recommended by the World
      Health Organization (WHO) to help early detection of drug resistant strains of
      the parasite and contain their rapid spread. The objective of this study was to
      assess the therapeutic efficacy of AL in a high-transmission setting in Ethiopia.
      The study site was Setit Humera, northwest Ethiopia. Single-arm prospective study
      of a 28-day follow-up was conducted from October 2014 to January 2015 according
      to the revised WHO 2009 drug efficacy study protocol. Study end-points were
      classified into primary end-point and secondary end-point. While the primary end
      point was the day-28 adequate clinical and parasitological response the secondary
      end-points were clinical and parasitological evaluations (parasite, fever and
      gametocyte clearance rate, incidence of drug adverse events) and the relative
      increment in hemoglobin (Hb) level from baseline to day (D) 14 and D28. A total
      of 92 patients were enrolled and 79 had completed the 28-day follow-up period.
      The overall cure rate was 98.8% with 95% confidence interval of 0.915-0.998
      without polymerase chain reaction correction. The parasite clearance rate was
      high with fast resolution of clinical symptoms; 100% of the study participants
      cleared parasitaemia and fever on D3. Gametocyte carriage was reduced from 7% on
      D0 to 1% on D3 and complete clearance was achieved on D14. Mean Hb concentration
      significantly increased on D28 compared to that on D14. There was no serious
      adverse event. AL was efficacious and safe in a high-transmission setting for
      treatment of uncomplicated falciparum malaria.

PMID- 28445505
TI  - Dominance of an alien shrub Rhus typhina over a native shrub Vitex negundo var.
      heterophylla under variable water supply patterns.
AB  - Temporal heterogeneity of a resource supply can have a profound effect on the
      interactions between alien and native plant species and their potential
      invasiveness. Precipitation patterns may be variable and result in a higher
      heterogeneity of water supply with global climate change. In this study, an alien
      shrub species, Rhus typhina, introduced to China from North America and a native
      shrub species, Vitex negundo var. heterophylla, were grown in monoculture and
      mixed culture under different water supply regimes, with four levels of water
      supply frequencies but with a constant level of total supplied water. After 60
      days of treatments, the alien species was found to be the superior competitor in
      the mixed culture and was unaffected by changes in the water supply pattern. The
      dominance of R. typhina was mainly owing to its greater biomass and effective
      modulation of leaf physiology. However, in the mixed culture, V. negundo var.
      heterophylla exhibited both leaf- and whole-plant-level acclimations, including
      higher leaf length to petiole length and root to shoot biomass ratios, and lower
      specific leaf weight and leaf length to leaf width ratio. Plant height of V.
      negundo var. heterophylla was comparable to that of R. typhina in the mixed
      culture, which is a strategy to escape shading. Although water treatments had
      little effect on most traits in both species, the possible influence of water
      regimes should not be neglected. Compared with high-frequency water supply
      treatments, more individuals of V. negundo var. heterophylla died in low-water
      frequency treatments when in competition with R. typhina, which may lead to
      species turnover in the field. The authors recommended that caution should be
      exercised when introducing R. typhina to non-native areas in the context of
      global climate change.

PMID- 28445506
TI  - Phenotype, function, and differentiation potential of human monocyte subsets.
AB  - Human monocytes have been grouped into classical (CD14++CD16-), non-classical
      (CD14dimCD16++), and intermediate (CD14++CD16+) subsets. Documentation of normal
      function and variation in this complement of subtypes, particularly their
      differentiation potential to dendritic cells (DC) or macrophages, remains
      incomplete. We therefore phenotyped monocytes from peripheral blood of healthy
      subjects and performed functional studies on high-speed sorted subsets. Subset
      frequencies were found to be tightly controlled over time and across individuals.
      Subsets were distinct in their secretion of TNFalpha, IL-6, and IL-1beta in
      response to TLR agonists, with classical monocytes being the most producers and
      non-classical monocytes the least. Monocytes, particularly those of the non
      classical subtype, secreted interferon-alpha (IFN-alpha) in response to
      intracellular TLR3 stimulation. After incubation with IL-4 and GM-CSF, classical
      monocytes acquired monocyte-derived DC (mo-DC) markers and morphology and
      stimulated allogeneic T cell proliferation in MLR; intermediate and non-classical
      monocytes did not. After incubation with IL-3 and Flt3 ligand, no subset
      differentiated to plasmacytoid DC. After incubation with GM-CSF (M1 induction) or
      macrophage colony-stimulating factor (M-CSF) (M2 induction), all subsets acquired
      macrophage morphology, secreted macrophage-associated cytokines, and displayed
      enhanced phagocytosis. From these studies we conclude that classical monocytes
      are the principal source of mo-DCs, but all subsets can differentiate to
      macrophages. We also found that monocytes, in particular the non-classical
      subset, represent an alternate source of type I IFN secretion in response to
      virus-associated TLR agonists.

PMID- 28445508
TI  - Error model of geomagnetic-field measurement and extended Kalman-filter based
      compensation method.
AB  - The real-time accurate measurement of the geomagnetic-field is the foundation to
      achieving high-precision geomagnetic navigation. The existing geomagnetic-field
      measurement models are essentially simplified models that cannot accurately
      describe the sources of measurement error. This paper, on the basis of
      systematically analyzing the source of geomagnetic-field measurement error, built
      a complete measurement model, into which the previously unconsidered geomagnetic
      daily variation field was introduced. This paper proposed an extended Kalman
      filter based compensation method, which allows a large amount of measurement data
      to be used in estimating parameters to obtain the optimal solution in the sense
      of statistics. The experiment results showed that the compensated strength of the
      geomagnetic field remained close to the real value and the measurement error was
      basically controlled within 5nT. In addition, this compensation method has strong
      applicability due to its easy data collection and ability to remove the
      dependence on a high-precision measurement instrument.

PMID- 28445507
TI  - Various mutations compensate for a deleterious lacZalpha insert in the
      replication enhancer of M13 bacteriophage.
AB  - M13 and other members of the Ff class of filamentous bacteriophages have been
      extensively employed in myriad applications. The Ph.D. series of phage-displayed
      peptide libraries were constructed from the M13-based vector M13KE. As a direct
      descendent of M13mp19, M13KE contains the lacZalpha insert in the intergenic
      region between genes IV and II, where it interrupts the replication enhancer of
      the (+) strand origin. Phage carrying this 816-nucleotide insert are viable, but
      propagate in E. coli at a reduced rate compared to wild-type M13 phage,
      presumably due to a replication defect caused by the insert. We have previously
      reported thirteen compensatory mutations in the 5'-untranslated region of gene
      II, which encodes the replication initiator protein gIIp. Here we report several
      additional mutations in M13KE that restore a wild-type propagation rate. Several
      clones from constrained-loop variable peptide libraries were found to have
      ejected the majority of lacZalpha gene in order to reconstruct the replication
      enhancer, albeit with a small scar. In addition, new point mutations in the gene
      II 5'-untranslated region or the gene IV coding sequence have been spontaneously
      observed or synthetically engineered. Through phage propagation assays, we
      demonstrate that all these genetic modifications compensate for the replication
      defect in M13KE and restore the wild-type propagation rate. We discuss the
      mechanisms by which the insertion and ejection of the lacZalpha gene, as well as
      the mutations in the regulatory region of gene II, influence the efficiency of
      replication initiation at the (+) strand origin. We also examine the presence and
      relevance of fast-propagating mutants in phage-displayed peptide libraries.

PMID- 28445511
TI  - Correction: Mental health and adjustment to juvenile idiopathic arthritis: Level
      of agreement between parent and adolescent reports according to Strengths and
      Difficulties Questionnaire and Adolescent Outcomes Questionnaire.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0173768.].

PMID- 28445509
TI  - Functional genetic variants within the SIRT2 gene promoter in acute myocardial
      infarction.
AB  - Coronary artery disease (CAD), including acute myocardial infarction (AMI) is the
      complication of atherosclerosis. Recently, genome-wide association studies have
      identified a large number of CAD-related genetic variants. However, only 10% of
      CAD cases could be explained. Low frequent and rare genetic variants have been
      recently proposed to be main causes for CAD. SIRT2 is a member of sirtuin family,
      NAD(+)-dependent class III deacetylases. SIRT2 is involved in genomic stability,
      metabolism, inflammation, oxidative stress and autophagy, as well as in platelet
      function. Thus, we hypothesized that genetic variants in SIRT2 gene may
      contribute to AMI. In this study, SIRT2 gene promoter was analyzed in large
      cohorts of AMI patients (n = 375) and ethnic-matched controls (n = 377). Three
      novel heterozygous DSVs (g.38900888_91delTAAA, g.38900270A>G and g.38899853C>T)
      were identified in three AMI patients, but in none of controls. These DSVs
      significantly altered the transcriptional activity of the SIRT2 gene promoter
      (P<0.05) in both HEK-293 and H9c2 cells. Five novel heterozygous DSVS
      (g.38900562C>T, g.38900413A>C, g.38900030G>A, g.38899925A>C and g.38899852C>T)
      were only found in controls, which did not significantly affected SIRT2 gene
      promoter activity (P>0.05). In addition, four novel heterozygous DSVs and five
      SNPs were found in both AMI patients and control with similar frequencies
      (P>0.05), two SNPs of which were examined and did not affect SIRT2 gene promoter
      activity (P>0.05). Taken together, the DSVs identified in AMI patients may change
      SIRT2 level by affecting the transcriptional activity of SIRT2 gene promoter,
      contributing to the AMI development as a rare risk factor.

PMID- 28445510
TI  - Whole genome re-sequencing to identify suppressor mutations of mutant and foreign
      Escherichia coli FtsZ.
AB  - FtsZ is an essential protein for bacterial cell division, where it forms the
      cytoskeletal scaffold and may generate the constriction force. We have found
      previously that some mutant and foreign FtsZ that do not complement an ftsZ null
      can function for cell division in E. coli upon acquisition of a suppressor
      mutation somewhere in the genome. We have now identified, via whole genome re
      sequencing, single nucleotide polymorphisms in 11 different suppressor strains.
      Most of the mutations are in genes of various metabolic pathways, which may
      modulate cell division indirectly. Mutations in three genes, ispA, accD and nlpI,
      may be more directly involved in cell division. In addition to the genomic
      suppressor mutations, we identified intragenic suppressors of three FtsZ point
      mutants (R174A, E250K and L272V).

PMID- 28445512
TI  - Proportions of circulating follicular helper T cells are reduced and correlate
      with memory B cells in HIV-infected children.
AB  - INTRODUCTION: HIV causes defects in memory B cells in children, but the
      mechanisms of those defects have not been fully elucidated. One possible
      mechanism is the lack of T-cell help to B cells during immune reactions. However,
      few studies have assessed the effect of HIV on follicular helper T cells (TFH
      cells) in children. METHODS: In this study, follicular-homing CD4 T cells and
      memory B cells were assessed in HIV-infected children and compared with children
      from the community. CXCR5 and CD45RO were used as markers of follicular-homing T
      cells and memory T cells, respectively. Memory TFH cells were identified as
      CD3+CD8-CD4+CXCR5+CD45RO+PD1+. Central memory T cells were identified based on
      CCR7 expression. Relationship between the proportions of follicular-homing CD4 T
      cells and memory B cells were determined in multivariable regression models.
      RESULTS: Highly viremic HIV-infected children had lower proportions of memory TFH
      cells when compared with community control children. In multivariable analyses,
      high proportions of memory TFH cells were associated with increased percentages
      of resting memory B cells after adjusting for other covariates. CONCLUSION: The
      impact of HIV on follicular helper T cells could influence the accumulation of
      memory B cells in HIV-infected children.

PMID- 28445513
TI  - Dietary patterns and all-cause, cancer, and cardiovascular disease mortality in
      Japanese men and women: The Japan public health center-based prospective study.
AB  - OBJECTIVE: A meta-analysis showed an inverse association of a prudent/healthy
      dietary pattern with all-cause mortality and no association of a
      western/unhealthy dietary pattern. However, the association of distinctive
      dietary patterns of Japanese population with mortality remains unclear. We
      prospectively investigated the association between dietary patterns and all
      cause, cancer, and cardiovascular disease mortality among Japanese adults.
      METHODS: Participants were 36,737 men and 44,983 women aged 45-74 years who
      participated in the second survey of the Japan Public Health Center-based
      Prospective Study (1995-1998) and who had no history of serious disease. Dietary
      patterns were derived from principal component analysis of the consumption of 134
      food and beverage items ascertained by a food frequency questionnaire. Hazard
      ratios of death from the second survey to December 2012 were estimated using cox
      proportional hazard regression analysis. RESULTS: A prudent dietary pattern,
      which was characterized by high intake of vegetables, fruit, soy products,
      potatoes, seaweed, mushrooms, and fish, was significantly associated with
      decreased risk of all-cause and cardiovascular disease mortality. The
      multivariable-adjusted hazard ratios (95% confidence intervals) of all-cause and
      cardiovascular disease mortality for the highest versus lowest quartile of the
      prudent dietary pattern score were 0.82 (0.77 to 0.86) and 0.72 (0.64 to 0.79),
      respectively (P for trend <0.001 in both). A Westernized dietary pattern,
      characterized by high intake of meat, processed meat, bread, and dairy products,
      was also inversely associated with risk of all-cause, cancer, and cardiovascular
      disease mortality. A traditional Japanese dietary pattern was not associated with
      these risks. CONCLUSIONS: The prudent and Westernized dietary patterns were
      associated with a decreased risk of all-cause and cardiovascular disease
      mortality in Japanese adults.

PMID- 28445514
TI  - The complexity underlying invasiveness precludes the identification of invasive
      traits: A comparative study of invasive and non-invasive heterocarpic Atriplex
      congeners.
AB  - Heterocarpy enables species to effectively spread under unfavourable conditions
      by producing two or more types of fruit differing in ecological characteristics.
      Although it is frequent in annuals occupying disturbed habitats that are
      vulnerable to invasion, there is still a lack of congeneric studies addressing
      the importance of heterocarpy for species invasion success. We compared two pairs
      of heterocarpic Atriplex species, each of them comprising one invasive and one
      non-invasive non-native congener. In two common garden experiments, we (i)
      simulated the influence of different levels of nutrients and population density
      on plants grown from different types of fruits and examined several traits that
      are generally positively associated with invasion success, and (ii) grew plants
      in a replacement series experiment to evaluate resource partitioning between them
      and to compare their competitive ability. We found that specific functional
      traits or competitiveness of species cannot explain the invasiveness of Atriplex
      species, indicating that species invasiveness involves more complex interactions
      of traits that are important only in certain ecological contexts, i.e. in
      specific environmental conditions and only some habitats. Interestingly, species
      trait differences related to invasion success were found between plants growing
      from the ecologically most contrasting fruit types. We suggest that fruit types
      differing in ecological behaviour may be essential in the process of invasion or
      in the general spreading of heterocarpic species, as they either the maximize
      population growth (type C fruit) or enhance the chance of survival of new
      populations (type A fruit). Congeners offer the best available methodical
      framework for comparing traits among phylogenetically closely related invasive
      and non-invasive species. However, as indicated by our results, this approach is
      unlikely to reveal invasive traits because of the complexity underlying
      invasiveness.

PMID- 28445516
TI  - Transplantation of induced mesenchymal stem cells for treating chronic renal
      insufficiency.
AB  - Discovering a new cell transplantation approach for treating chronic renal
      insufficiency is a goal of many nephrologists. In vitro-cultured peripheral blood
      mononuclear cells (PBMCs) were reprogrammed into induced mesenchymal stem cells
      (iMSCs) by using natural inducing agents made in our laboratory. The stem cell
      phenotype of the iMSCs was then identified. Unilateral ureteral obstruction (UUO)
      was used to create an animal model of chronic renal insufficiency characterized
      by renal interstitial fibrosis. The induced and non-induced PBMCs were
      transplanted, and the efficacy of iMSCs in treating chronic renal insufficiency
      was evaluated using a variety of methods. The ultimate goal was to explore the
      effects of iMSC transplantation on the treatment of chronic renal insufficiency,
      with the aim of providing a new therapeutic modality for this disease.

PMID- 28445515
TI  - Correlation of histopathologic characteristics to protein expression and function
      in malignant melanoma.
AB  - BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers,
      which upon progression has neither a prognostic marker nor a specific and lasting
      treatment. Proteomic analysis is a versatile approach with high throughput data
      and results that can be used for characterizing tissue samples. However, such
      analysis is hampered by the complexity of the disease, heterogeneity of patients,
      tumors, and samples themselves. With the long term aim of quest for better
      diagnostics biomarkers, as well as predictive and prognostic markers, we focused
      on relating high resolution proteomics data to careful histopathological
      evaluation of the tumor samples and patient survival information. PATIENTS AND
      METHODS: Regional lymph node metastases obtained from ten patients with
      metastatic melanoma (stage III) were analyzed by histopathology and proteomics
      using mass spectrometry. Out of the ten patients, six had clinical follow-up
      data. The protein deep mining mass spectrometry data was related to the
      histopathology tumor tissue sections adjacent to the area used for deep-mining.
      Clinical follow-up data provided information on disease progression which could
      be linked to protein expression aiming to identify tissue-based specific protein
      markers for metastatic melanoma and prognostic factors for prediction of
      progression of stage III disease. RESULTS: In this feasibility study, several
      proteins were identified that positively correlated to tumor tissue content
      including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also
      identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor
      tissue content. Other proteins were inversely correlated to tumor tissue content,
      the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of
      proteins were significantly related to clinical outcome, among these, HEXB, PKM
      and GPNMB stood out, as hallmarks of processes involved in progression from stage
      III to stage IV disease and poor survival. CONCLUSION: In this feasibility study,
      promising results show the feasibility of relating proteomics to histopathology
      and clinical outcome, and insight thus can be gained into the molecular processes
      driving the disease. The combined analysis of histological features including the
      sample cellular composition with protein expression of each metastasis enabled
      the identification of novel, differentially expressed proteins. Further studies
      are necessary to determine whether these putative biomarkers can be utilized in
      diagnostics and prognostic prediction of metastatic melanoma.

PMID- 28445517
TI  - Motivation factors for suicidal behavior and their clinical relevance in admitted
      psychiatric patients.
AB  - BACKGROUND: Suicidal behavior (SB) is a major, worldwide health concern. To date
      there is limited understanding of the associated motivational aspects which
      accompany this self-initiated conduct. AIMS: To develop a method for identifying
      motivational features associated with SB by studying admitted psychiatric
      patients, and to examine their clinical relevance. METHODS: By performing a
      factor analytic study using data obtained from a patient sample exhibiting high
      suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was
      constructed to measure the features. Data included assessments of DSM-IV
      psychiatric and personality disorders, suicide intent, depressive symptomatology,
      overt aggression, recent life events (RLEs) and methods of SB, collated from
      structured interviews. Association of identified features with clinical variables
      was examined by correlation analyses and MANCOVA. RESULTS: Factor analyses
      elicited a 4-factor solution composed of Interpersonal-testing (IT),
      Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These
      factors were classified according to two distinctions, namely interpersonal vs.
      intra-personal directedness, and the level of assumed influence by SB or the
      relationship to prevailing emotions. Analyses revealed meaningful links between
      patient features and clinical variables. Interpersonal-motivations (IT and IC)
      were associated with overt aggression, low suicidality and RLE discord or
      conflict, while SR was associated with depression, high suicidality and RLE
      separation or death. Borderline personality disorder showed association with IC
      and SS. When self-strangulation was set as a reference SB method, self-cutting
      and overdose-taking were linked to IT and SS, respectively. CONCLUSIONS: The
      factors extracted in this study largely corresponded to factors from previous
      studies, implying that they may be useful in a wider clinical context. The
      association of these features with SB-related factors suggests that they
      constitute an integral part of the process leading to SB. These results provide a
      base for further research into clinical strategies for patient management and
      therapy.

PMID- 28445518
TI  - Use of human fat grafting in the prevention of perineural adherence: Experimental
      study in athymic mouse.
AB  - : Perineural adherences represent a problem after surgery involving peripheral
      neural system. Fat-grafting with adipose derived stem cells (ASCs) with their pro
      regenerative characteristics can be important to prevent the neural damage or to
      facilitate the neural regeneration. Our idea was to use the fat-grafting as an
      anti-adherence device and test its efficacy on a postsurgical scar animal model
      and comparing to an antiadhesive gel. 32 athymic mice were operated under
      magnification, we exposed both sciatic nerves. We randomly divided all sciatic
      nerves into four experimental groups: burning (1), burning + carboxy
      methylcellulose and poly- ethylene oxide (CMC-PEO) (2) + human adipose fat tissue
      (3), control group (4). Bio-mechanical evaluation was performed to measure the
      peak force required to pull out the nerve from the muscular bed. RESULTS: in the
      CMC-PEO group the peak pull out force was 0.37 Newton. In the fat grafted group
      we registered a peak pull out force of 0.35 N (t Student 0.913). In burning group
      the force necessary to tear the nerve apart was markedly superior (0.46 N). In
      control group, we reported the minimal strength (0.31 N) to slide the nerve from
      the tissue. Histologically, in the group treated with fat-grating, a thinner scar
      layer was highlighted. Considering the results of this study we can support the
      efficacy in animal experimental model of fat graft as an anti-adherence device in
      peripheral nerve surgery.

PMID- 28445519
TI  - The effect of atomoxetine on random and directed exploration in humans.
AB  - The adaptive regulation of the trade-off between pursuing a known reward
      (exploitation) and sampling lesser-known options in search of something better
      (exploration) is critical for optimal performance. Theory and recent empirical
      work suggest that humans use at least two strategies for solving this dilemma: a
      directed strategy in which choices are explicitly biased toward information
      seeking, and a random strategy in which decision noise leads to exploration by
      chance. Here we examined the hypothesis that random exploration is governed by
      the neuromodulatory locus coeruleus-norepinephrine system. We administered
      atomoxetine, a norepinephrine transporter blocker that increases extracellular
      levels of norepinephrine throughout the cortex, to 22 healthy human participants
      in a double-blind crossover design. We examined the effect of treatment on
      performance in a gambling task designed to produce distinct measures of directed
      exploration and random exploration. In line with our hypothesis we found an
      effect of atomoxetine on random, but not directed exploration. However, contrary
      to expectation, atomoxetine reduced rather than increased random exploration. We
      offer three potential explanations of our findings, involving the non-linear
      relationship between tonic NE and cognitive performance, the interaction of
      atomoxetine with other neuromodulators, and the possibility that atomoxetine
      affected phasic norepinephrine activity more so than tonic norepinephrine
      activity.

PMID- 28445520
TI  - Serum irisin levels correlated to peritoneal dialysis adequacy in nondiabetic
      peritoneal dialysis patients.
AB  - BACKGROUND: Irisin is a recently discovered myokine thought to be involved in
      multiple metabolism abnormalities in most dialysis patients. However, the myokine
      has not been thoroughly studied in peritoneal dialysis. This study aimed to
      evaluate serum irisin levels and establish their relation to dialysis adequacy,
      insulin resistance, and bone metabolism status in patients on peritoneal
      dialysis. METHODS: A total of 59 nondiabetic prevalent peritoneal dialysis
      patients and 52 age- and sex-matched healthy controls were enrolled in this cross
      sectional study. Serum irisin concentration was assessed by enzyme-linked
      immunosorbent assay. The correlations between serum irisin and dialysis adequacy,
      clinical, and metabolic variables were investigated. RESULTS: Serum irisin levels
      were lower in nondiabetic peritoneal dialysis patients (17.02ng/ml) compared with
      healthy controls (22.17ng/ml, P<0.001). Multivariate regression analysis revealed
      that fasting glucose levels were correlated inversely with serum irisin levels in
      peritoneal dialysis patients. Serum irisin levels were associated with neither
      insulin resistance nor bone metabolism in our patients. Serum irisin levels were
      positively associated with peritoneal Kt/Vurea (beta = 4.933, 95% confidence
      interval [CI] = 0.536-9.331, P = 0.029) and peritoneal CCr (beta = 0.259, 95% CI
      = 0.053-0.465, P = 0.015) among peritoneal dialysis patients. CONCLUSIONS: The
      study demonstrated that non-diabetic peritoneal dialysis patients have lower
      serum irisin levels, and the levels were correlated with peritoneal dialysis
      adequacy, indicating adequate dialysis may improve irisin secretion. Additional
      studies are needed to provide a confirmation.

PMID- 28445521
TI  - Next generation sequencing to dissect the genetic architecture of KNG1 and F11
      loci using factor XI levels as an intermediate phenotype of thrombosis.
AB  - Venous thromboembolism is a complex disease with a high heritability. There are
      significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and
      F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that
      might account for the variability of FXI levels. The KNG1 and F11 loci were
      sequenced completely in 110 unrelated individuals from the GAIT-2 (Genetic
      Analysis of Idiopathic Thrombophilia 2) Project using Next Generation Sequencing
      on an Illumina MiSeq. The GAIT-2 Project is a study of 935 individuals in 35
      extended Spanish families selected through a proband with idiopathic
      thrombophilia. Among the 110 individuals, a subset of 40 individuals was chosen
      as a discovery sample for identifying variants. A total of 762 genetic variants
      were detected. Several significant associations were established among common
      variants and low-frequency variants sets in KNG1 and F11 with FXI levels using
      the PLINK and SKAT packages. Among these associations, those of rs710446 and five
      low-frequency variant sets in KNG1 with FXI level variation were significant
      after multiple testing correction and permutation. Also, two putative pathogenic
      mutations related to high and low FXI levels were identified by data filtering
      and in silico predictions. This study of KNG1 and F11 loci should help to
      understand the connection between genotypic variation and variation in FXI
      levels. The functional genetic variants should be useful as markers of
      thromboembolic risk.

PMID- 28445522
TI  - Revealing phenotype-associated functional differences by genome-wide scan of
      ancient haplotype blocks.
AB  - Genome-wide scans for positive selection have become important for genomic
      medicine, and many studies aim to find genomic regions affected by positive
      selection that are associated with risk allele variations among populations. Most
      such studies are designed to detect recent positive selection. However, we
      hypothesize that ancient positive selection is also important for adaptation to
      pathogens, and has affected current immune-mediated common diseases. Based on
      this hypothesis, we developed a novel linkage disequilibrium-based pipeline,
      which aims to detect regions associated with ancient positive selection across
      populations from single nucleotide polymorphism (SNP) data. By applying this
      pipeline to the genotypes in the International HapMap project database, we show
      that genes in the detected regions are enriched in pathways related to the immune
      system and infectious diseases. The detected regions also contain SNPs reported
      to be associated with cancers and metabolic diseases, obesity-related traits,
      type 2 diabetes, and allergic sensitization. These SNPs were further mapped to
      biological pathways to determine the associations between phenotypes and
      molecular functions. Assessments of candidate regions to identify functions
      associated with variations in incidence rates of these diseases are needed in the
      future.

PMID- 28445523
TI  - Preventive child health care at elementary school age: The costs of routine
      assessments with a triage approach.
AB  - BACKGROUND: Triage in Preventive Child Health Care (PCH) assessments could
      further the efficient use of human resources and budgets and therefore make extra
      care possible for children with specific needs. We assessed the costs of routine
      PCH assessments with and without triage for children aged 5/6 years and 10/11
      years. In a triage approach, PCH assistants conduct pre-assessments to identify
      children requiring follow-up assessments by a physician or nurse. In the usual
      approach, all children are assessed by a physician and an assistant (children
      aged 5/6 years) or a nurse (children aged 10/11 years). METHODS: All the direct
      costs of conducting routine PCH assessments with the triage and usual approach
      were assessed using a bottom-up micro-costing approach. In four PCH services in
      the Netherlands, two using triage and two the usual approach, professionals
      completed questionnaires about time spent on assessments, including time related
      to non-attendance at assessments, the referral of children and administration.
      RESULTS: The projected costs for PCH professionals working on PCH assessments
      amounted to ?5.2 million per cohort of 100,000 children aged 5/6 years in the
      triage approach, and ?7.6 million in the usual approach. The projected costs in
      both approaches for children aged 10/11 years were about ?4 million per 100,000
      children. CONCLUSION: The triage approach to PCH resulted in a projected cost
      reduction of about one-third, compared with usual practice, for routine
      assessments by physicians of children aged 5/6 years. There are minimal cost
      savings in the group of children aged 10/11 years when nurses are involved and so
      other considerations such as workforce shortages would be required to justify a
      change to a triage approach. Further research is needed to investigate the
      differences in costs of care after the completion of the routine assessments.

PMID- 28445525
TI  - Correction: Lower levels of uric acid and striatal dopamine in non-tremor
      dominant Parkinson's disease subtype.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0174644.].

PMID- 28445524
TI  - Live imaging of primary ocular vasculature formation in zebrafish.
AB  - Ocular vasculature consists of the central retinal and ciliary vascular systems,
      which are essential to maintaining visual function. Many researchers have
      attempted to determine their origins and development; however, the detailed,
      stepwise process of ocular vasculature formation has not been established. In
      zebrafish, two angioblast clusters, the rostral and midbrain organizing centers,
      form almost all of the cranial vasculature, including the ocular vasculature, and
      these are from where the cerebral arterial and venous angioblast clusters,
      respectively, differentiate. In this study, we first determined the anatomical
      architecture of the primary ocular vasculature and then followed its path from
      the two cerebral angioblast clusters using a time-lapse analysis of living
      Tg(flk1:EGFP)k7 zebrafish embryos, in which the endothelial cells specifically
      expressed enhanced green fluorescent protein. We succeeded in capturing images of
      the primary ocular vasculature formation and were able to determine the origin of
      each ocular vessel. In zebrafish, the hyaloid and ciliary arterial systems first
      organized independently, and then anastomosed via the inner optic circle on the
      surface of the lens by the lateral transfer of the optic vein. Finally, the
      choroidal vascular plexus formed around the eyeball to complete the primary
      ocular vasculature formation. To our knowledge, this study is the first to report
      successful capture of circular integration of the optic artery and vein, lateral
      transfer of the optic vein to integrate the hyaloidal and superficial ocular
      vasculatures, and formation of the choroidal vascular plexus. Furthermore, this
      new morphological information enables us to assess the entire process of the
      primary ocular vasculature formation, which will be useful for its precise
      understanding.

PMID- 28445526
TI  - Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon
      rubescens is catalyzed by a pair of diterpene synthases.
AB  - Plants produce an immense diversity of natural products (i.e. secondary or
      specialized metabolites) that offer a rich source of known and potentially new
      pharmaceuticals and other desirable bioproducts. The Traditional Chinese
      Medicinal plant Isodon rubescens (Lamiaceae) contains an array of bioactive
      labdane-related diterpenoid natural products. Of these, the ent-kauranoid
      oridonin is the most prominent specialized metabolite that has been extensively
      studied for its potent antimicrobial and anticancer efficacy. Mining of a
      previously established transcriptome of I. rubescens leaf tissue identified seven
      diterpene synthase (diTPSs) candidates. Here we report the functional
      characterization of four I. rubescens diTPSs. IrTPS5 and IrTPS3 were identified
      as an ent-copalyl diphosphate (CPP) synthase and a (+)-CPP synthase,
      respectively. Distinct transcript abundance of IrTPS5 and the predicted ent-CPP
      synthase IrTPS1 suggested a role of IrTPS5 in specialized ent-kaurene metabolism
      possibly en route to oridonin. Nicotiana benthamiana co-expression assays
      demonstrated that IrTPS4 functions sequentially with IrTPS3 to form miltiradiene.
      In addition, IrTPS2 converted the IrTPS3 product (+)-CPP into the hydroxylated
      tricyclic diterpene nezukol not previously identified in I. rubescens. Metabolite
      profiling verified the presence of nezukol in I. rubescens leaf tissue. The
      proposed IrTPS2-catalyzed reaction mechanism proceeds via the common ionization
      of the diphosphate group of (+)-CPP, followed by formation of an intermediary
      pimar-15-en-8-yl+ carbocation and neutralization of the carbocation by water
      capture at C-8 to yield nezukol, as confirmed by nuclear magnetic resonance (NMR)
      analysis. Oxygenation activity is rare for the family of class I diTPSs and
      offers new catalysts for developing metabolic engineering platforms to produce a
      broader spectrum of bioactive diterpenoid natural products.

PMID- 28445527
TI  - Enhanced functional connectivity and volume between cognitive and reward centers
      of naive rodent brain produced by pro-dopaminergic agent KB220Z.
AB  - Dopaminergic reward dysfunction in addictive behaviors is well supported in the
      literature. There is evidence that alterations in synchronous neural activity
      between brain regions subserving reward and various cognitive functions may
      significantly contribute to substance-related disorders. This study presents the
      first evidence showing that a pro-dopaminergic nutraceutical (KB220Z)
      significantly enhances, above placebo, functional connectivity between reward and
      cognitive brain areas in the rat. These include the nucleus accumbens, anterior
      cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic
      loci. Significant functional connectivity, increased brain connectivity volume
      recruitment (potentially neuroplasticity), and dopaminergic functionality were
      found across the brain reward circuitry. Increases in functional connectivity
      were specific to these regions and were not broadly distributed across the brain.
      While these initial findings have been observed in drug naive rodents, this
      robust, yet selective response implies clinical relevance for addicted
      individuals at risk for relapse, who show reductions in functional connectivity
      after protracted withdrawal. Future studies will evaluate KB220Z in animal models
      of addiction.

PMID- 28445528
TI  - Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity
      by inducing HO-1.
AB  - OBJECTIVE: beta-Cell dysfunction plays a central role in the pathogenesis of type
      2 diabetes (T2D), and the identification of novel approaches to improve beta-cell
      function is essential to treat this disease. Baicalein, a flavonoid originally
      isolated from the root of Scutellaria Baicalensis, has been shown to have
      beneficial effects on beta-cell function. Here, the authors investigated the
      molecular mechanism responsible for the protective effects of baicalein against
      palmitate (PA)-induced impaired beta-cell function, and placed focus on the role
      of heme oxygenase (HO)-1. METHODS: Rat pancreatic beta-cell line INS-1 cells or
      mouse pancreatic islets were cultured with PA (500 MUM) to induce lipotoxicity in
      the presence or absence of baicalein (50 MUM), and the expressions of the ER
      stress markers, ATF-3, CHOP and GRP78 were detected by Western blotting and/or
      qPCR. The involvement of HO-1 was evaluated by HO-1 siRNA transfection and using
      the HO-1 inhibitor ZnPP. RESULTS: Baicalein reduced PA-induced ER stress and
      inflammation and enhanced insulin secretion, and these effects were associated
      with the induction of HO-1. Furthermore, these protective effects were attenuated
      by ZnPP and by HO-1 siRNA. Pretreatment of PD98059 (an ERK inhibitor)
      significantly inhibited the protective effects of baicalein and blocked HO-1
      induction. On the other hand, CO production by RuCO (a CO donor) ameliorated PA
      induced ER stress, suggesting that CO production followed by HO-1 induction may
      contribute to the protective effects of baicalein against PA-induced beta-cell
      dysfunction. CONCLUSION: Baicalein protects pancreatic beta-cells from PA-induced
      ER stress and inflammation via an ERK-HO-1 dependent pathway. The authors suggest
      HO-1 induction in pancreatic beta-cells appears to be a promising therapeutic
      strategy for T2D.

PMID- 28445529
TI  - Ductular reaction correlates with fibrogenesis but does not contribute to liver
      regeneration in experimental fibrosis models.
AB  - BACKGROUND AND AIMS: Ductular reaction is a standard component of fibrotic liver
      tissue but its function is largely unknown. It is supposed to interact with the
      matrix producing myofibroblasts and compensate the declining regenerative
      capacity of hepatocytes. The relationship between the extent of fibrosis-ductular
      reaction, proliferative activity of hepatocytes and ductular reaction were
      studied sequentially in experimental hepatic fibrosis models. METHODS: Liver
      fibrosis/cirrhosis was induced in wild type and TGFbeta overproducing transgenic
      mice by carbon tetrachloride and thioacetamide administration. The effect of
      thioacetamide was modulated by treatment with imatinib and erlotinib. The extent
      of ductular reaction and fibrosis was measured by morphometry following
      cytokeratin 19 immunofluorescent labeling and Picro Sirius staining respectively.
      The proliferative activity of hepatocytes and ductular reaction was evaluated by
      BrdU incorporation. The temporal distribution of the parameters was followed and
      compared within and between different experimental groups. RESULTS: There was a
      strong significant correlation between the extent of fibrosis and ductular
      reaction in each experimental group. Although imatinib and erlotinib temporarily
      decreased fibrosis this effect later disappeared. We could not observe negative
      correlation between the proliferation of hepatocytes and ductular reaction in any
      of the investigated models. CONCLUSIONS: The stringent connection between
      ductular reaction and fibrosis, which cannot be influenced by any of our
      treatment regimens, suggests that there is a close mutual interaction between
      them instead of a unidirectional causal relationship. Our results confirm a close
      connection between DR and fibrogenesis. However, since the two parameters changed
      together we could not establish a causal relationship and were unable to reveal
      which was the primary event. The lack of inverse correlation between the
      proliferation of hepatocytes and ductular reaction questions that ductular
      reaction can compensate for the failing regenerative activity of hepatocytes. No
      evidences support the persistent antifibrotic property of imatinib or erlotinib.

PMID- 28445530
TI  - Computation of adherence to medication and visualization of medication histories
      in R with AdhereR: Towards transparent and reproducible use of electronic
      healthcare data.
AB  - Adherence to medications is an important indicator of the quality of medication
      management and impacts on health outcomes and cost-effectiveness of healthcare
      delivery. Electronic healthcare data (EHD) are increasingly used to estimate
      adherence in research and clinical practice, yet standardization and transparency
      of data processing are still a concern. Comprehensive and flexible open-source
      algorithms can facilitate the development of high-quality, consistent, and
      reproducible evidence in this field. Some EHD-based clinical decision support
      systems (CDSS) include visualization of medication histories, but this is rarely
      integrated in adherence analyses and not easily accessible for data exploration
      or implementation in new clinical settings. We introduce AdhereR, a package for
      the widely used open-source statistical environment R, designed to support
      researchers in computing EHD-based adherence estimates and in visualizing
      individual medication histories and adherence patterns. AdhereR implements a set
      of functions that are consistent with current adherence guidelines, definitions
      and operationalizations. We illustrate the use of AdhereR with an example dataset
      of 2-year records of 100 patients and describe the various analysis choices
      possible and how they can be adapted to different health conditions and types of
      medications. The package is freely available for use and its implementation
      facilitates the integration of medication history visualizations in open-source
      CDSS platforms.

PMID- 28445531
TI  - AntagomiR-451 inhibits oxygen glucose deprivation (OGD)-induced HUVEC necrosis
      via activating AMPK signaling.
AB  - Oxygen glucose deprivation (OGD) application in cultured human umbilical vein
      endothelial cells (HUVECs) mimics ischemic injuries. AntagomiR-451, the miroRNA
      451 ("miR-451") inhibitor, could activate pro-survival AMP-activated protein
      kinase (AMPK) signaling. In the current study, we showed that forced-expression
      of antagomiR-451 depleted miRNA-451 and significantly attenuated OGD-induced
      necrosis of HUVECs. Activation of AMPK was required for antagomiR-451-mediated
      pro-survival actions. AMPK inhibition, by AMPKalpha shRNA or dominant negative
      mutation, almost completely abolishedantagomiR-451-mediated HUVEC protection
      again OGD. Reversely, forced-activation of AMPK by exogenous expression of
      constructively-active AMPKalpha inhibited OGD-induced HUVEC necrosis. At the
      molecular level, antagomiR-451 expression in HUVECs inhibited OGD-induced
      programmed necrosis, the latter was evidenced by mitochondrial p53-cyclophilinD
      (Cyp-D) association, mitochondrial depolarization as well as reactive oxygen
      species (ROS) production and lactate dehydrogenase (LDH) breach. Together, we
      suggest that antagomiR-451 activates AMPK to inhibit OGD-induced programmed
      necrosis in HUVECs.

PMID- 28445532
TI  - Use of molecular markers in identification and characterization of resistance to
      rice blast in India.
AB  - Rice blast disease caused by Magnaporthe oryzae is one of the most destructive
      disease causing huge losses to rice yield in different parts of the world.
      Therefore, an attempt has been made to find out the resistance by screening and
      studying the genetic diversity of eighty released rice varieties by National Rice
      Research Institute, Cuttack (NRVs) using molecular markers linked to twelve major
      blast resistance (R) genes viz Pib, Piz, Piz-t, Pik, Pik-p, Pikm Pik-h, Pita/Pita
      2, Pi2, Pi9, Pi1 and Pi5. Out of which, nineteen varieties (23.75%) showed
      resistance, twenty one were moderately resistant (26.25%) while remaining forty
      varieties (50%) showed susceptible in uniform blast nursery. Rice varieties
      possessing blast resistance genes varied from four to twelve and the frequencies
      of the resistance genes ranged from 0 to 100%. The cluster analysis grouped the
      eighty NRVs into two major clusters at 63% level of genetic similarity
      coefficient. The PIC value for seventeen markers varied from 0 to 0.37 at an
      average of 0.20. Out of seventeen markers, only five markers, 195R-1, Pi9-i,
      Pita3, YL155/YL87 and 40N23r corresponded to three broad spectrum R genes viz.
      Pi9, Pita/Pita2 and Pi5 were found to be significantly associated with the blast
      disease with explaining phenotypic variance from 3.5% to 7.7%. The population
      structure analysis and PCoA divided the entire 80 NRVs into two sub-groups. The
      outcome of this study would help to formulate strategies for improving rice blast
      resistance through genetic studies, plant-pathogen interaction, identification of
      novel R genes, development of new resistant varieties through marker-assisted
      breeding for improving rice blast resistance in India and worldwide.

PMID- 28445533
TI  - Influence of temperature on daily locomotor activity in the crab Uca pugilator.
AB  - Animals living in the intertidal zone are exposed to prominent temperature
      changes. To cope with the energetic demands of environmental thermal challenges,
      ectotherms rely mainly on behavioral responses, which may change depending on the
      time of the day and seasonally. Here, we analyze how temperature shapes crabs'
      behavior at 2 different times of the year and show that a transition from
      constant cold (13.5 degrees C) to constant warm (17.5 degrees C) water
      temperature leads to increased locomotor activity levels throughout the day in
      fiddler crabs (Uca pugilator) collected during the summer. In contrast, the same
      transition in environmental temperature leads to a decrease in the amplitude of
      the daily locomotor activity rhythm in crabs collected during the winter. In
      other words, colder temperatures during the cold season favor a more prominent
      diurnal behavior. We interpret this winter-summer difference in the response of
      daily locomotor activity to temperature changes within the framework of the
      circadian thermoenergetics hypothesis, which predicts that a less favorable
      energetic balance would promote a more diurnal activity pattern. During the
      winter, when the energetic balance is likely less favorable, crabs would save
      energy by being more active during the expected high-temperature phase of the day
      light phase-and less during the expected low-temperature phase of the day-dark
      phase. Our results suggest that endogenous rhythms in intertidal ectotherms
      generate adaptive behavioral programs to cope with thermoregulatory demands of
      the intertidal habitat.

PMID- 28445534
TI  - A new, high-resolution global mass coral bleaching database.
AB  - Episodes of mass coral bleaching have been reported in recent decades and have
      raised concerns about the future of coral reefs on a warming planet. Despite the
      efforts to enhance and coordinate coral reef monitoring within and across
      countries, our knowledge of the geographic extent of mass coral bleaching over
      the past few decades is incomplete. Existing databases, like ReefBase, are
      limited by the voluntary nature of contributions, geographical biases in data
      collection, and the variations in the spatial scale of bleaching reports. In this
      study, we have developed the first-ever gridded, global-scale historical coral
      bleaching database. First, we conducted a targeted search for bleaching reports
      not included in ReefBase by personally contacting scientists and divers
      conducting monitoring in under-reported locations and by extracting data from the
      literature. This search increased the number of observed bleaching reports by
      79%, from 4146 to 7429. Second, we employed spatial interpolation techniques to
      develop annual 0.04 degrees  * 0.04 degrees  latitude-longitude global maps of
      the probability that bleaching occurred for 1985 through 2010. Initial results
      indicate that the area of coral reefs with a more likely than not (>50%) or
      likely (>66%) probability of bleaching was eight times higher in the second half
      of the assessed time period, after the 1997/1998 El Nino. The results also
      indicate that annual maximum Degree Heating Weeks, a measure of thermal stress,
      for coral reefs with a high probability of bleaching increased over time. The
      database will help the scientific community more accurately assess the change in
      the frequency of mass coral bleaching events, validate methods of predicting mass
      coral bleaching, and test whether coral reefs are adjusting to rising ocean
      temperatures.

PMID- 28445536
TI  - Assessment of dental ontogeny in late Miocene hipparionines from the Lamagou
      fauna of Fugu, Shaanxi Province, China.
AB  - A collection of 28 hipparionine skull and mandible fossils with a dated age of
      approximately 7.4 Ma from Fugu, Shaanxi, northwestern China (belonging to
      Hipparion chiai and Hipparion cf. coelophyes) shows an age distribution in a
      successive development sequence. By observing the dentitions in these fossil
      materials, knowledge of dental ontogeny has been gained, such as the opening time
      of the posterior wall of post-fossettes, the displacement of the plis hypostyle,
      the morphologic changes of the protocone and hypocone, etc. Additionally, 4
      isolated maxillary cheek teeth and 2 mandibular cheek teeth were cut into slices
      in the traditional manner for authentication. These discoveries indicate that
      both of the hipparionine species in the Lamagou fauna are Hipparion cf. chiai
      exactly and offer further insight into the morphologic changes that occur during
      dental wear in hipparionines, which may greatly promote the morphological and
      taxonomic study of hipparionine species.

PMID- 28445535
TI  - microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection and
      targets NTAN1.
AB  - BACKGROUND: Legionella pneumophila (L. pneumophila) is a causative agent of
      severe pneumonia. It is highly adapted to intracellular replication and
      manipulates host cell functions like vesicle trafficking and mRNA translation to
      its own advantage. However, it is still unknown to what extent microRNAs (miRNAs)
      are involved in the Legionella-host cell interaction. METHODS: WT and MyD88-/-
      murine bone marrow-derived macrophages (BMM) were infected with L. pneumophila,
      the transcriptome was analyzed by high throughput qPCR array (microRNAs) and
      conventional qPCR (mRNAs), and mRNA-miRNA interaction was validated by luciferase
      assays with 3'-UTR mutations and western blot. RESULTS: L. pneumophila infection
      caused a pro-inflammatory reaction and significant miRNA changes in murine
      macrophages. In MyD88-/- cells, induction of inflammatory markers, such as
      Ccxl1/Kc, Il6 and miR-146a-5p was reduced. Induction of miR-125a-3p was
      completely abrogated in MyD88-/- cells. Target prediction analyses revealed N
      terminal asparagine amidase 1 (NTAN1), a factor from the n-end rule pathway, to
      be a putative target of miR-125a-3p. This interaction could be confirmed by
      luciferase assay and western blot. CONCLUSION: Taken together, we characterized
      the miRNA regulation in L. pneumophila infection with regard to MyD88 signaling
      and identified NTAN1 as a target of miR-125a-3p. This finding unravels a yet
      unknown feature of Legionella-host cell interaction, potentially relevant for new
      treatment options.

PMID- 28445537
TI  - Predicting epidemic evolution on contact networks from partial observations.
AB  - The massive employment of computational models in network epidemiology calls for
      the development of improved inference methods for epidemic forecast. For simple
      compartment models, such as the Susceptible-Infected-Recovered model, Belief
      Propagation was proved to be a reliable and efficient method to identify the
      origin of an observed epidemics. Here we show that the same method can be applied
      to predict the future evolution of an epidemic outbreak from partial observations
      at the early stage of the dynamics. The results obtained using Belief Propagation
      are compared with Monte Carlo direct sampling in the case of SIR model on random
      (regular and power-law) graphs for different observation methods and on an
      example of real-world contact network. Belief Propagation gives in general a
      better prediction that direct sampling, although the quality of the prediction
      depends on the quantity under study (e.g. marginals of individual states,
      epidemic size, extinction-time distribution) and on the actual number of observed
      nodes that are infected before the observation time.

PMID- 28445538
TI  - Gene expression patterns associated with neurological disease in human HIV
      infection.
AB  - The pathogenesis and nosology of HIV-associated neurological disease (HAND)
      remain incompletely understood. Here, to provide new insight into the molecular
      events leading to neurocognitive impairments (NCI) in HIV infection, we analyzed
      pathway dysregulations in gene expression profiles of HIV-infected patients with
      or without NCI and HIV encephalitis (HIVE) and control subjects. The Gene Set
      Enrichment Analysis (GSEA) algorithm was used for pathway analyses in conjunction
      with the Molecular Signatures Database collection of canonical pathways (MSigDb).
      We analyzed pathway dysregulations in gene expression profiles of patients from
      the National NeuroAIDS Tissue Consortium (NNTC), which consists of samples from 3
      different brain regions, including white matter, basal ganglia and frontal cortex
      of HIV-infected and control patients. While HIVE is characterized by widespread,
      uncontrolled inflammation and tissue damage, substantial gene expression evidence
      of induction of interferon (IFN), cytokines and tissue injury is apparent in all
      brain regions studied, even in the absence of NCI. Various degrees of white
      matter changes were present in all HIV-infected subjects and were the primary
      manifestation in patients with NCI in the absence of HIVE. In particular, NCI in
      patients without HIVE in the NNTC sample is associated with white matter
      expression of chemokines, cytokines and beta-defensins, without significant
      activation of IFN. Altogether, the results identified distinct pathways
      differentially regulated over the course of neurological disease in HIV infection
      and provide a new perspective on the dynamics of pathogenic processes in the
      course of HIV neurological disease in humans. These results also demonstrate the
      power of the systems biology analyses and indicate that the establishment of
      larger human gene expression profile datasets will have the potential to provide
      novel mechanistic insight into the pathogenesis of neurological disease in HIV
      infection and identify better therapeutic targets for NCI.

PMID- 28445539
TI  - Restless legs syndrome and cardiovascular diseases: A case-control study.
AB  - OBJECTIVE: The association between restless legs syndrome (RLS), cardiovascular
      diseases (CVD) and hypertension is inconsistent. This case-control study examined
      i) the association between primary RLS, CVD and hypertension by taking into
      account many potential confounders and ii) the influence of RLS duration,
      severity and treatment, sleep and depressive symptoms on CVD and hypertension in
      primary RLS. METHODS: A standardized questionnaire to assess the RLS phenotype,
      history of CVD and hypertension, sleep and depressive symptoms, drug intake and
      demographic/clinical features was sent to the France-Ekbom Patients Association
      members. A CVD event was defined as a self-reported history of coronary heart
      disease, heart failure, arrhythmia or stroke. Hypertension was also self
      assessed. Current treatment for hypertension and arrhythmia also defined
      underlying hypertension and arrhythmia. Controls without RLS and without
      consanguinity were chosen by the patients. RESULTS: 487 patients with primary RLS
      (median age 71 years; 67.4% women) and 354 controls (68 years, 47.7% women) were
      included. Most of the patients (91.7%) were treated for RLS, especially with
      dopaminergic agonists. The median age of RLS onset was 45 years. CVD and
      hypertension were associated with RLS in unadjusted association, but not after
      adjustment for age, sex and body mass index. Patients with RLS and with CVD
      and/or hypertension were significantly older, with hypercholesterolemia, sleep
      apnea and older age at RLS and at daily RLS onset compared with patients without
      CVD and/or hypertension. No significant difference was found for other RLS
      features, ferritin levels, daytime sleepiness, insomnia and depressive symptoms.
      CONCLUSION: Despite some limitations in the design of this study, we found that
      most of the treated patients for primary RLS had no association with CVD and
      hypertension after controlling for key potential confounders. Comorbid CVD or
      hypertension was associated with cardiovascular risk factors, but not with RLS
      features except for older age at onset.

PMID- 28445540
TI  - Individuals with severely impaired vision can learn useful orientation and
      mobility skills in virtual streets and can use them to improve real street
      safety.
AB  - Virtual reality has great potential in training road safety skills to individuals
      with low vision but the feasibility of such training has not been demonstrated.
      We tested the hypotheses that low vision individuals could learn useful skills in
      virtual streets and could apply them to improve real street safety. Twelve
      participants, whose vision was too poor to use the pedestrian signals were taught
      by a certified orientation and mobility specialist to determine the safest time
      to cross the street using the visual and auditory signals made by the start of
      previously stopped cars at a traffic-light controlled street intersection. Four
      participants were trained in real streets and eight in virtual streets presented
      on 3 projection screens. The crossing timing of all participants was evaluated in
      real streets before and after training. The participants were instructed to say
      "GO" at the time when they felt the safest to cross the street. A safety score
      was derived to quantify the GO calls based on its occurrence in the pedestrian
      phase (when the pedestrian sign did not show DON'T WALK). Before training, > 50%
      of the GO calls from all participants fell in the DON'T WALK phase of the traffic
      cycle and thus were totally unsafe. 20% of the GO calls fell in the latter half
      of the pedestrian phase. These calls were unsafe because one initiated crossing
      this late might not have sufficient time to walk across the street. After
      training, 90% of the GO calls fell in the early half of the pedestrian phase.
      These calls were safer because one initiated crossing in the pedestrian phase and
      had at least half of the pedestrian phase for walking across. Similar safety
      changes occurred in both virtual street and real street trained participants. An
      ANOVA showed a significant increase of the safety scores after training and there
      was no difference in this safety improvement between the virtual street and real
      street trained participants. This study demonstrated that virtual reality-based
      orientation and mobility training could be as efficient as real street training
      in improving street safety in individuals with severely impaired vision.

PMID- 28445541
TI  - IQGAP1 is an oncogenic target in canine melanoma.
AB  - Canine oral mucosal melanoma is an aggressive malignant neoplasm and is
      characterized by local infiltration and a high metastatic potential. The disease
      progression is similar to that of human oral melanomas. Whereas human cutaneous
      melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%),
      human mucosal melanoma harbors these mutations much less frequently. This makes
      therapeutic targeting and research modeling of the oral form potentially
      different from that of the cutaneous form in humans. Similarly, research has
      found only rare Nras mutations and no activating Braf mutations in canine oral
      melanomas, but they are still reliant on MAPK signaling. IQGAP1 is a signaling
      scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras- and Raf-
      driven cancers, including melanomas. To investigate whether IQGAP1 is a potential
      target in canine melanoma, we examined the expression and localization of IQGAP1
      in primary canine melanomas and canine oral melanoma cell lines obtained from the
      University of California-Davis. Using CRISPR/Cas9 knockout of IQGAP1, we examined
      effects on downstream ERK1/2 pathway activity and assayed proliferation of cell
      lines when treated with a peptide that blocks the interaction between IQGAP1 and
      ERK1/2. We observed that canine IQGAP1 is expressed and localizes to a similar
      extent in both human and canine melanoma by qPCR, Western blot, and
      immunofluorescence. Deletion of IQGAP1 reduces MAPK pathway activation in cell
      lines, similar to effects seen in human BrafV600E cell lines. Additionally, we
      demonstrated reduced proliferation when these cells are treated with a blocking
      peptide in vitro.

PMID- 28445542
TI  - No-touch radiofrequency ablation using multiple electrodes: An in vivo comparison
      study of switching monopolar versus switching bipolar modes in porcine livers.
AB  - OBJECTIVE: To evaluate the in vivo technical feasibility, efficiency, and safety
      of switching bipolar (SB) and switching monopolar (SM) radiofrequency ablation
      (RFA) as a no-touch ablation technique in the porcine liver. MATERIALS AND
      METHODS: The animal care and use committee approved this animal study and 16 pigs
      were used in two independent experiments. In the first experiment, RFA was
      performed on 2-cm tumor mimickers in the liver using a no-touch technique in the
      SM mode (2 groups, SM1: 10 minutes, n = 10; SM2: 15 minutes, n = 10) and SB-mode
      (1 group, SB: 10 minutes, n = 10). The technical success with sufficient safety
      margins, creation of confluent necrosis, ablation size, and distance between the
      electrode and ablation zone margin (DEM), were compared between groups. In the
      second experiment, thermal injury to the adjacent anatomic organs was compared
      between SM-RFA (15 minutes, n = 13) and SB-RFA modes (10 minutes, n = 13).
      RESULTS: The rates of the technical success and the creation of confluent
      necrosis were higher in the SB group than in the SM1 groups (100% vs. 60% and 90%
      vs. 40%, both p < 0.05). The ablation volume in the SM2 group was significantly
      larger than that in the SB group (59.2+/-18.7 cm3 vs. 39.8+/-9.7 cm3, p < 0.05),
      and the DEM in the SM2 group was also larger than that in the SB group (1.39+/
      0.21 cm vs. 1.07+/-0.10 cm, p < 0.05). In the second experiment, the incidence of
      thermal injury to the adjacent organs and tissues in the SB group (23.1%, 3/13)
      was significantly lower than that in the SM group (69.2%, 8/13) (p = 0.021).
      CONCLUSION: SB-RFA was more advantageous for a no-touch technique for liver
      tumors, showing the potential of a better safety profile than SM-RFA.

PMID- 28445543
TI  - Comparative genomic analysis between Corynebacterium pseudotuberculosis strains
      isolated from buffalo.
AB  - Corynebacterium pseudotuberculosis is a Gram-positive, pleomorphic, facultative
      intracellular pathogen that causes Oedematous Skin Disease (OSD) in buffalo. To
      better understand the pathogenic mechanisms of OSD, we performed a comparative
      genomic analysis of 11 strains of C. pseudotuberculosis isolated from different
      buffalo found to be infected in Egypt during an outbreak that occurred in 2008.
      Sixteen previously described pathogenicity islands (PiCp) were present in all of
      the new buffalo strains, but one of them, PiCp12, had an insertion that contained
      both a corynephage and a diphtheria toxin gene, both of which may play a role in
      the adaptation of C. pseudotuberculosis to this new host. Synteny analysis showed
      variations in the site of insertion of the corynephage during the same outbreak.
      A gene functional comparison showed the presence of a nitrate reductase operon
      that included genes involved in molybdenum cofactor biosynthesis, which is
      necessary for a positive nitrate reductase phenotype and is a possible adaptation
      for intracellular survival. Genomes from the buffalo strains also had fusions in
      minor pilin genes in the spaA and spaD gene cluster (spaCX and spaYEF), which
      could suggest either an adaptation to this particular host, or mutation events in
      the immediate ancestor before this particular epidemic. A phylogenomic analysis
      confirmed a clear separation between the Ovis and Equi biovars, but also showed
      what appears to be a clustering by host species within the Equi strains.

PMID- 28445544
TI  - Pressure flaking to serrate bifacial points for the hunt during the MIS5 at
      Sibudu Cave (South Africa).
AB  - Projectile technology is considered to appear early in the southern African
      Middle Stone Age (MSA) and the rich and high resolution MSA sequence of Sibudu
      Cave in KwaZulu-Natal has provided many new insights about the use and hafting of
      various projectile forms. We present the results of a functional and
      technological analysis on a series of unpublished serrated bifacial points
      recently recovered from the basal deposits of Sibudu Cave. These serrated tools,
      which only find equivalents in the neighbouring site of Umhlatuzana, precede the
      Still Bay techno-complex and are older than 77 ka BP. Independent residue and use
      wear analyses were performed in a phased procedure involving two separate
      analysts, which allowed the engagement between two separate lines of functional
      evidence. Thanks to the excellent preservation at Sibudu Cave, a wide range of
      animal, plant and mineral residues were observed in direct relation with
      diagnostic wear patterns. The combination of technological, wear and residue
      evidence allowed us to confirm that the serration was manufactured with bone
      compressors and that the serrated points were mounted with a composite adhesive
      as the tips of projectiles used in hunting activities. The suite of technological
      and functional data pushes back the evidence for the use of pressure flaking
      during the MSA and highlights the diversity of the technical innovations adopted
      by southern African MSA populations. We suggest the serrated points from the
      stratigraphic units Adam to Darya of Sibudu illustrate one important
      technological adaptation of the southern African MSA and provide another example
      of the variability of MSA bifacial technologies.

PMID- 28445545
TI  - Correction: Characterisation of liver fat in the UK Biobank cohort.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0172921.].

PMID- 28445547
TI  - Correction: An Automated, Experimenter-Free Method for the Standardised, Operant
      Cognitive Testing of Rats.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0169476.].

PMID- 28445546
TI  - A coral-algal phase shift in Mesoamerica not driven by changes in herbivorous
      fish abundance.
AB  - Coral-algal phase shifts in which coral cover declines to low levels and is
      replaced by algae have often been documented on coral reefs worldwide. This has
      motivated coral reef management responses that include restriction and regulation
      of fishing, e.g. herbivorous fish species. However, there is evidence that
      eutrophication and sedimentation can be at least as important as a reduction in
      herbivory in causing phase shifts. These threats arise from coastal development
      leading to increased nutrient and sediment loads, which stimulate algal growth
      and negatively impact corals respectively. Here, we first present results of a
      dynamic process-based model demonstrating that in addition to overharvesting of
      herbivorous fish, bottom-up processes have the potential to precipitate coral
      algal phase shifts on Mesoamerican reefs. We then provide an empirical example
      that exemplifies this on coral reefs off Mahahual in Mexico, where a shift from
      coral to algal dominance occurred over 14 years, during which there was little
      change in herbivore biomass but considerable development of tourist
      infrastructure. Our results indicate that coastal development can compromise the
      resilience of coral reefs and that watershed and coastal zone management together
      with the maintenance of functional levels of fish herbivory are critical for the
      persistence of coral reefs in Mesoamerica.

PMID- 28445548
TI  - Assessing the severity of sleep apnea syndrome based on ballistocardiogram.
AB  - BACKGROUND: Sleep Apnea Syndrome (SAS) is a common sleep-related breathing
      disorder, which affects about 4-7% males and 2-4% females all around the world.
      Different approaches have been adopted to diagnose SAS and measure its severity,
      including the gold standard Polysomnography (PSG) in sleep study field as well as
      several alternative techniques such as single-channel ECG, pulse oximeter and so
      on. However, many shortcomings still limit their generalization in home
      environment. In this study, we aim to propose an efficient approach to
      automatically assess the severity of sleep apnea syndrome based on the
      ballistocardiogram (BCG) signal, which is non-intrusive and suitable for in home
      environment. METHODS: We develop an unobtrusive sleep monitoring system to
      capture the BCG signals, based on which we put forward a three-stage sleep apnea
      syndrome severity assessment framework, i.e., data preprocessing, sleep-related
      breathing events (SBEs) detection, and sleep apnea syndrome severity evaluation.
      First, in the data preprocessing stage, to overcome the limits of BCG signals
      (e.g., low precision and reliability), we utilize wavelet decomposition to obtain
      the outline information of heartbeats, and apply a RR correction algorithm to
      handle missing or spurious RR intervals. Afterwards, in the event detection
      stage, we propose an automatic sleep-related breathing event detection algorithm
      named Physio_ICSS based on the iterative cumulative sums of squares (i.e., the
      ICSS algorithm), which is originally used to detect structural breakpoints in a
      time series. In particular, to efficiently detect sleep-related breathing events
      in the obtained time series of RR intervals, the proposed algorithm not only
      explores the practical factors of sleep-related breathing events (e.g., the limit
      of lasting duration and possible occurrence sleep stages) but also overcomes the
      event segmentation issue (e.g., equal-length segmentation method might divide one
      sleep-related breathing event into different fragments and lead to incorrect
      results) of existing approaches. Finally, by fusing features extracted from
      multiple domains, we can identify sleep-related breathing events and assess the
      severity level of sleep apnea syndrome effectively. CONCLUSIONS: Experimental
      results on 136 individuals of different sleep apnea syndrome severities validate
      the effectiveness of the proposed framework, with the accuracy of 94.12%
      (128/136).

PMID- 28445549
TI  - Impact of the c-MybE308G mutation on mouse myelopoiesis and dendritic cell
      development.
AB  - Booreana mice carrying the c-Myb308G point mutation were analyzed to determine
      changes in early hematopoiesis in the bone marrow and among mature cells in the
      periphery. This point mutation led to increased numbers of early hematopoietic
      stem and progenitor cells (HSPCs), with a subsequent reduction in the development
      of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid
      cells and granulocytes. Myelopoiesis was further investigated by way of
      particular subsets affected. A specific question addressed whether booreana mice
      contained increased numbers of dendritic-like cells (L-DC subset) recently
      identified in the spleen, since L-DCs arise in vitro by direct differentiation
      from HSPCs co-cultured over splenic stroma. The non-lethal c-Myb mutation in
      booreana mice was associated with significantly lower representation of splenic
      CD8- conventional dendritic cells (cDCs), inflammatory monocytes, and neutrophils
      compared to wild-type mice. This result confirmed the bone marrow origin of
      progenitors for these subsets since c-Myb is essential for their development.
      Production of L-DCs and resident monocytes was not affected by the c-MybE308G
      mutation. These subsets may derive from different progenitors than those in bone
      marrow, and are potentially established in the spleen during embryogenesis. An
      alternative explanation may be needed for why there was no change in CD8+ cDCs in
      booreana spleen since these cells are known to derive from common dendritic
      progenitors in bone marrow.

PMID- 28445550
TI  - Classifying patents based on their semantic content.
AB  - In this paper, we extend some usual techniques of classification resulting from a
      large-scale data-mining and network approach. This new technology, which in
      particular is designed to be suitable to big data, is used to construct an open
      consolidated database from raw data on 4 million patents taken from the US patent
      office from 1976 onward. To build the pattern network, not only do we look at
      each patent title, but we also examine their full abstract and extract the
      relevant keywords accordingly. We refer to this classification as semantic
      approach in contrast with the more common technological approach which consists
      in taking the topology when considering US Patent office technological classes.
      Moreover, we document that both approaches have highly different topological
      measures and strong statistical evidence that they feature a different model.
      This suggests that our method is a useful tool to extract endogenous information.

PMID- 28445552
TI  - Correction: Should All Women with Polycystic Ovary Syndrome Be Screened for
      Metabolic Parameters?: A Hospital-Based Observational Study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0167036.].

PMID- 28445551
TI  - Pattern classification of EEG signals reveals perceptual and attentional states.
AB  - Pattern classification techniques have been widely used to differentiate neural
      activity associated with different perceptual, attentional, or other cognitive
      states, often using fMRI, but more recently with EEG as well. Although these
      methods have identified EEG patterns (i.e., scalp topographies of EEG signals
      occurring at certain latencies) that decode perceptual and attentional states on
      a trial-by-trial basis, they have yet to be applied to the spatial scope of
      attention toward global or local features of the display. Here, we initially used
      pattern classification to replicate and extend the findings that perceptual
      states could be reliably decoded from EEG. We found that visual perceptual
      states, including stimulus location and object category, could be decoded with
      high accuracy peaking between 125-250 ms, and that the discriminative
      spatiotemporal patterns mirrored and extended our (and other well-established)
      ERP results. Next, we used pattern classification to investigate whether
      spatiotemporal EEG signals could reliably predict attentional states, and
      particularly, the scope of attention. The EEG data were reliably differentiated
      for local versus global attention on a trial-by-trial basis, emerging as a
      specific spatiotemporal activation pattern over posterior electrode sites during
      the 250-750 ms interval after stimulus onset. In sum, we demonstrate that
      multivariate pattern analysis of EEG, which reveals unique spatiotemporal
      patterns of neural activity distinguishing between behavioral states, is a
      sensitive tool for characterizing the neural correlates of perception and
      attention.

PMID- 28445553
TI  - A novel rat head gaze determination system based on optomotor responses.
AB  - The optomotor response of animals is commonly used to measure their visual
      performance, e.g., rats of different genetically altered strains or various drug
      tests. With the presentation of stimuli using computer screens or projectors, the
      common idea focuses on measuring the eye movement or head and/or body movement to
      characterize changes of the head gaze. However, traditional methods rely on
      either the invasive fixation of animals, or the judgment of a human observer who
      reports the stimulus-tracking movements. In this paper, we propose a novel head
      gaze determination system to automatically track the head movement of rats
      without artificial markers. The experiments were done to demonstrate the process
      of optimizing parameters in image processing. As a result, the head angle curve
      of the proposed method is consistent with that of ground-truth data annotated
      manually according to predefined rules. Hence, the proposed method provides a
      simple, convenient, and objective solution to automatically generate the head
      gaze orientations from massive amounts of recorded data for further visual
      performance analysis.

PMID- 28445554
TI  - Correction: Integrating the effects of latitude and altitude on the spatial
      differentiation of plant community diversity in a mountainous ecosystem in China.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0174231.].

PMID- 28445556
TI  - Allostasis and the Epigenetics of Brain and Body Health Over the Life Course: The
      Brain on Stress.

PMID- 28445555
TI  - Drug-eluting balloon versus bare-mental stent and drug-eluting stent for de novo
      coronary artery disease: A systematic review and meta-analysis of 14 randomized
      controlled trials.
AB  - BACKGROUND: Drug-eluting balloon (DEB) has become an alternative option to drug
      eluting stent (DES) for the treatment of in-stent restenosis (ISR). However, the
      effect of drug-eluting balloon with regular bare-mental stent (BMS) in de novo
      coronary artery disease (CAD) is unclear. This meta-analysis aimed to evaluate
      the efficacy of DEB with regular BMS compared to BMS or DES in de novo CAD.
      METHODS: Randomized controlled trials (RCTs) assessing the efficacy of DEB+BMS in
      comparison with BMS or DES were obtained by searching the PubMed, EMBASE, and
      Cochrane Library databases through January 2016. Primary endpoints were major
      adverse cardiac events (MACEs) and late lumen loss (LLL). Secondary endpoints
      included death, myocardial infarction (MI), target lesion revascularization
      (TLR), stent thrombosis (ST), binary restenosis, and minimum lumen diameter
      (MLD). Dichotomous and continuous data were presented as odds ratios (ORs) and
      mean differences (MDs) with 95% confidence intervals (CIs), respectively, and
      analyzed using a random-effects model. RESULTS: A total of 14 RCTs involving 2281
      patients were included in this meta-analysis. DEB+BMS showed significantly less
      MACEs (OR: 0.67, 95%CI 0.45 to 0.99, P = 0.04) and reduced LLL (MD: -0.30 mm,
      95%CI: -0.48 mm to -0.11 mm, P = 0.001) compared with BMS. Meanwhile, treatment
      with DEB+BMS had disadvantages over DES in terms of MACEs (OR: 1.94, 95%CI 1.24
      to 3.05, P = 0.004), LLL (MD: 0.20 mm, 95%CI: 0.07 mm to 0.33 mm, P = 0.003), TLR
      (OR: 2.53, 95% CI 1.36 to 4.72, P = 0.003), and MLD (MD: -0.25 mm, 95%CI: -0.42
      mm to -0.09 mm, P = 0.003). CONCLUSIONS: This limited evidence demonstrated that
      treatment with DEB+BMS appears to be effective in de novo CAD. In addition, DEB+
      BMS clearly showed superiority to BMS, but is inferior to DES in the treatment of
      patients with de novo CAD. Hence, DES (especially new generation DES) should be
      recommended for patients with de novo CAD.

PMID- 28445557
TI  - US Adult Illicit Cannabis Use, Cannabis Use Disorder, and Medical Marijuana Laws:
      1991-1992 to 2012-2013.
AB  - Importance: Over the last 25 years, illicit cannabis use and cannabis use
      disorders have increased among US adults, and 28 states have passed medical
      marijuana laws (MML). Little is known about MML and adult illicit cannabis use or
      cannabis use disorders considered over time. Objective: To present national data
      on state MML and degree of change in the prevalence of cannabis use and
      disorders. Design, Participants, and Setting: Differences in the degree of change
      between those living in MML states and other states were examined using 3 cross
      sectional US adult surveys: the National Longitudinal Alcohol Epidemiologic
      Survey (NLAES; 1991-1992), the National Epidemiologic Survey on Alcohol and
      Related Conditions (NESARC; 2001-2002), and the National Epidemiologic Survey on
      Alcohol and Related Conditions-III (NESARC-III; 2012-2013). Early-MML states
      passed MML between NLAES and NESARC ("earlier period"). Late-MML states passed
      MML between NESARC and NESARC-III ("later period"). Main Outcomes and Measures:
      Past-year illicit cannabis use and DSM-IV cannabis use disorder. Results:
      Overall, from 1991-1992 to 2012-2013, illicit cannabis use increased
      significantly more in states that passed MML than in other states (1.4-percentage
      point more; SE, 0.5; P = .004), as did cannabis use disorders (0.7-percentage
      point more; SE, 0.3; P = .03). In the earlier period, illicit cannabis use and
      disorders decreased similarly in non-MML states and in California (where
      prevalence was much higher to start with). In contrast, in remaining early-MML
      states, the prevalence of use and disorders increased. Remaining early-MML and
      non-MML states differed significantly for use (by 2.5 percentage points; SE, 0.9;
      P = .004) and disorder (1.1 percentage points; SE, 0.5; P = .02). In the later
      period, illicit use increased by the following percentage points: never-MML
      states, 3.5 (SE, 0.5); California, 5.3 (SE, 1.0); Colorado, 7.0 (SE, 1.6); other
      early-MML states, 2.6 (SE, 0.9); and late-MML states, 5.1 (SE, 0.8). Compared
      with never-MML states, increases in use were significantly greater in late-MML
      states (1.6-percentage point more; SE, 0.6; P = .01), California (1.8-percentage
      point more; SE, 0.9; P = .04), and Colorado (3.5-percentage point more; SE, 1.5;
      P = .03). Increases in cannabis use disorder, which was less prevalent, were
      smaller but followed similar patterns descriptively, with change greater than
      never-MML states in California (1.0-percentage point more; SE, 0.5; P = .06) and
      Colorado (1.6-percentage point more; SE, 0.8; P = .04). Conclusions and
      Relevance: Medical marijuana laws appear to have contributed to increased
      prevalence of illicit cannabis use and cannabis use disorders. State-specific
      policy changes may also have played a role. While medical marijuana may help
      some, cannabis-related health consequences associated with changes in state
      marijuana laws should receive consideration by health care professionals and the
      public.

PMID- 28445558
TI  - Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex
      With Special Emphasis on Shagreen Patches.
AB  - Importance: Patients with tuberous sclerosis complex (TSC) frequently develop
      collagenous connective tissue nevi. The prototypical lesion is a large shagreen
      patch located on the lower back, but some patients only manifest small
      collagenomas or have lesions elsewhere on the body. The ability to recognize
      these variable presentations can be important for the diagnosis of TSC.
      Objective: To describe the clinical characteristics of connective tissue nevi on
      the trunk and extremities of patients with tuberous sclerosis complex. Design,
      Setting, and Participants: A retrospective analysis of patient medical records
      and skin photography was performed; 104 adult patients with TSC were enrolled in
      an observational cohort study that was enriched for those with pulmonary
      lymphangioleiomyomatosis, and was therefore composed mostly of women (99 women, 5
      men). All patients included were examined at the National Institutes of Health
      (NIH) in Bethesda, Maryland, from 1998 to 2013. Connective tissue nevi were
      categorized per anatomic location and size. Lesions less than 1 cm in diameter
      were termed collagenomas. Shagreen patches were characterized as small (1 to <4
      cm), medium (4 to <8 cm), and large (>=8 cm). Main Outcome and Measures:
      Frequency, anatomic location, size, and histological appearance of connective
      tissue nevi in patients with TSC. Results: Overall, 58 of 104 patients (median
      [range] age, 42 [19-70] years) with TSC (56%) had at least 1 connective tissue
      nevus on the trunk or thighs; of these, 28 of 58 patients (48%) had a solitary
      lesion, and 30 of 58 patients (52%) had 2 or more lesions. Overall, 120 lesions
      from 55 patients were classified by size; 46 lesions (38%) were collagenomas; 39
      lesions (32%) were small shagreen patches; 21 lesions (18%), medium shagreen
      patches; and 14 lesions (12%), large shagreen patches. The distribution of
      lesions was 9% (n = 11), upper back; 29% (n = 35), middle back; 51% (n = 61),
      lower back; and 11% (n = 13), other locations. All 26 shagreen patches that were
      analyzed histopathologically had coarse collagen fibers and 24 of 26 stained with
      Miller elastic stain had decreased elastic fibers. On immunoblot analysis,
      fibroblasts grown from shagreen patches expressed higher levels of phosphorylated
      ribosomal protein S6 than paired fibroblasts from normal-appearing skin.
      Conclusions and Relevance: Tuberous sclerosis complex-related connective tissue
      nevi are not limited to the lower back, and occasionally present on the central
      or upper back, buttocks, or thighs. Elastic fibers are typically decreased.
      Recognition of these variable presentations can be important for TSC diagnosis.

PMID- 28445560
TI  - Intensity of Statin Treatment and Mortality-Reply.

PMID- 28445559
TI  - Association of US Centers for Medicare and Medicaid Services Hospital 30-Day Risk
      Standardized Readmission Metric With Care Quality and Outcomes After Acute
      Myocardial Infarction: Findings From the National Cardiovascular Data
      Registry/Acute Coronary Treatment and Intervention Outcomes Network Registry-Get
      With the Guidelines.
AB  - Importance: The US Centers for Medicare and Medicaid Services Hospital
      Readmissions Reduction Program penalizes hospitals with higher-than-expected risk
      adjusted 30-day readmission rates (excess readmission ratio [ERR] > 1) after
      acute myocardial infarction (MI). However, the association of ERR with MI care
      processes and outcomes are not well established. Objective: To evaluate the
      association between ERR for MI with in-hospital process of care measures and 1
      year clinical outcomes. Design, Setting, and Participants: Observational analysis
      of hospitalized patients with MI from National Cardiovascular Data Registry/Acute
      Coronary Treatment and Intervention Outcomes Network Registry-Get With the
      Guidelines centers subject to the first cycle of the Hospital Readmissions
      Reduction Program between July 1, 2008, and June 30, 2011. Exposures: The ERR for
      MI (MI-ERR) in 2011. Main Outcomes and Measures: Adherence to process of care
      measures during index hospitalization in the overall study population and risk of
      the composite outcome of mortality or all-cause readmission within 1 year of
      discharge and its individual components among participants with available Centers
      for Medicare and Medicaid Services-linked data. Results: The median ages of
      patients in the MI-ERR greater than 1 and tertiles 1, 2, and 3 of the MI-ERR
      greater than 1 groups were 64, 63, 64, and 63 years, respectively. Among 380
      hospitals that treated a total of 176 644 patients with MI during the study
      period, 43% had MI-ERR greater than 1. The proportions of patients of black race,
      those with heart failure signs at admission, and bleeding complications increased
      with higher MI-ERR. There was no significant association between adherence to MI
      performance measures and MI-ERR (adjusted odds ratio, 0.94; 95% CI, 0.81-1.08,
      per 0.1-unit increase in MI-ERR for overall defect-free care). Among the 51 453
      patients with 1-year outcomes data available, higher MI-ERR was associated with
      higher adjusted risk of the composite outcome and all-cause readmission within 1
      year of discharge. This association was largely driven by readmissions early
      after discharge and was not significant in landmark analyses beginning 30 days
      after discharge. The MI-ERR was not associated with risk for mortality within 1
      year of discharge in the overall and 30-day landmark analyses. Conclusions and
      Relevance: During the first cycle of the Hospital Readmissions Reduction Program,
      participating hospitals' risk-adjusted 30-day readmission rates following MI were
      not associated with in-hospital quality of MI care or clinical outcomes occurring
      after the first 30 days after discharge.

PMID- 28445562
TI  - Systems Research in Psychiatric Neuroscience.

PMID- 28445561
TI  - Allegations of Failure to Obtain Informed Consent in Spinal Surgery Medical
      Malpractice Claims.
AB  - Importance: Predictive factors associated with increased risk of medical
      malpractice litigation have been identified, including severity of injury,
      physician sex, and error in diagnosis. However, there is a paucity of literature
      investigating informed consent in spinal surgery malpractice. Objective: To
      investigate the failure to obtain informed consent as an allegation in medical
      malpractice claims for patients undergoing a spinal procedure. Design, Setting,
      and Participants: In this retrospective cohort study, a national medicolegal
      database was searched for malpractice claim cases related to spinal surgery for
      all years available (ie, January 1, 1980, through December 31, 2015). Main
      Outcomes and Measures: Failure to obtain informed consent and associated medical
      malpractice case verdict. Results: A total of 233 patients (117 [50.4%] male and
      116 [49.8%] female; 80 with no informed consent allegation and 153 who cited lack
      of informed consent) who underwent spinal surgery and filed a malpractice claim
      were studied (mean [SD] age, 47.1 [13.1] years in the total group, 45.8 [12.9]
      years in the control group, and 47.9 [13.3] years in the informed consent group).
      Median interval between year of surgery and year of verdict was 5.4 years
      (interquartile range, 4-7 years). The most common informed consent allegations
      were failure to explain risks and adverse effects of surgery (52 [30.4%]) and
      failure to explain alternative treatment options (17 [9.9%]). In bivariate
      analysis, patients in the control group were more likely to require additional
      surgery (45 [56.3%] vs 53 [34.6%], P = .002) and have more permanent injuries
      compared with the informed consent group (46 [57.5%] vs 63 [42.0%], P = .03). On
      multivariable regression analysis, permanent injuries were more often associated
      with indemnity payment after a plaintiff verdict (odds ratio [OR], 3.12; 95% CI,
      1.46-6.65; P = .003) or a settlement (OR, 6.26; 95% CI, 1.06-36.70; P = .04).
      Informed consent allegations were significantly associated with less severe
      (temporary or emotional) injury (OR, 0.52; 95% CI, 0.28-0.97; P = .04). In
      addition, allegations of informed consent were found to be predictive of a
      defense verdict vs a plaintiff ruling (OR, 0.41; 95% CI, 0.17-0.98; P = .046) or
      settlement (OR, 0.01; 95% CI, 0.001-0.15; P < .001). Conclusions and Relevance:
      Lack of informed consent is an important cause of medical malpractice litigation.
      Although associated with a lower rate of indemnity payments, malpractice
      lawsuits, including informed consent allegations, still present a time, money,
      and reputation toll for physicians. The findings of this study can therefore help
      to improve preoperative discussions to protect spinal surgeons from malpractice
      claims and ensure that patients are better informed.

PMID- 28445564
TI  - Intensity of Statin Treatment and Mortality.

PMID- 28445563
TI  - Outbreak of Occupational Dermatitis Associated With Pyemotes ventricosus.
AB  - Importance: Although Pyemotes species have been known to cause dermatitis, recent
      reports are rare. During the past 30 years, only 3 outbreaks of dermatitis caused
      by Pyemotes ventricosus have been reported. Objective: To analyze the causative
      agent of skin changes in employees of a company that produced herbal medicines.
      Design, Setting, and Participants: This case series includes 18 patients (8 men,
      10 women; mean age, 44 years) who contracted unusual dermatitis after an
      occupational exposure in July and August of 2012 while working for a company that
      produced herbal medicines. The patients were examined at the Lower Silesia
      Regional Centre of Occupational Medicine in Wroclaw, Poland. Exposures: Workers
      weighed and packed 1 part of the Helichrysum arenarium herb. Main Outcomes and
      Measures: We hypothesized the causative agent to be P ventricosus. An examination
      of the herbal specimens for ectoparasites confirmed the diagnosis. Results:
      Initially 16 employees developed pruritic skin changes. Skin lesions with
      pruritic vesicles on an erythematous base with surrounding swelling and edema
      were observed. Several employees also developed a flulike illness. After 44 days,
      2 new employees presented with the same skin changes. The analysis of working
      conditions showed that the same part of the H arenarium herb was weighed and
      packed at that time. Conclusions and Relevance: We found that changing the time
      when the herbs were weighed and abandoning gas fumigation containing methyl
      bromide resulted in the recurrence of an almost forgotten disease.

PMID- 28445565
TI  - Annular Flaccid Pustules on the Trunk.

PMID- 28445567
TI  - Emergency General Surgery Needs for Lesbian, Gay, Bisexual, and Transgender
      Patients: Are We Prepared?

PMID- 28445566
TI  - Variation in Outcomes at Bariatric Surgery Centers of Excellence.
AB  - Importance: In the United States, reports about perioperative complications
      associated with bariatric surgery led to the establishment of accreditation
      criteria for bariatric centers of excellence and many bariatric centers obtaining
      accreditation. Currently, most bariatric procedures occur at these centers, but
      to what extent they uniformly provide high-quality care remains unknown.
      Objective: To describe the variation in surgical outcomes across bariatric
      centers of excellence and the geographic availability of high-quality centers.
      Design, Setting, and Participants: This retrospective review analyzed the claims
      data of 145 527 patients who underwent bariatric surgery at bariatric centers of
      excellence between January 1, 2010, and December 31, 2013. Data were obtained
      from the Healthcare Cost and Utilization Project's State Inpatient Database. This
      database included unique hospital identification numbers in 12 states (Arkansas,
      Arizona, Florida, Iowa, Massachusetts, Maryland, North Carolina, Nebraska, New
      Jersey, New York, Washington, and Wisconsin), allowing comparisons among 165
      centers of excellence located in those states. Participants were identified using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes. Those included in the study cohort were patients with a primary diagnosis
      of morbid obesity and who underwent laparoscopic Roux-en-Y gastric bypass, open
      Roux-en-Y gastric bypass, laparoscopic gastric band placement, or laparoscopic
      sleeve gastrectomy. Excluded from the cohort were patients younger than 18 years
      or who had an abdominal malignant neoplasm. Data were analyzed July 1, 2016,
      through January 10, 2017. Main Outcomes and Measures: Risk-adjusted and
      reliability-adjusted serious complication rates within 30 days of the index
      operation were calculated for each center. Centers were stratified by geographic
      location and operative volume. Results: In this analysis of claims data from 145
      527 patients, wide variation in quality was found across 165 bariatric centers of
      excellence, both nationwide and statewide. At the national level, the risk
      adjusted and reliability-adjusted serious complication rates at each center
      varied 17-fold, ranging from 0.6% to 10.3%. At the state level, variation ranged
      from 2.1-fold (Wisconsin decile range, 1.5%-3.3%) to 9.5-fold (Nebraska decile
      range, 1.0%-10.3%). After dividing hospitals into quintiles of quality on the
      basis of their adjusted complication rates, 38 of 132 (28.8%) had a center in a
      higher quintile of quality located within the same hospital service area.
      Variation in rates of complications existed at centers with low volume (annual
      mean [SD] procedure volume, 156 [20] patients; complication range, 0.6%-6.4%; 9.8
      fold variation), medium volume (annual mean [SD] procedure volume, 239 [27]
      patients; complication range, 0.6%-10.3%; 17.5-fold variation), and high volume
      (annual mean [SD] procedure volume, 448 [131] patients; complication range, 0.6%
      4.9%; 7.5-fold variation). Conclusions and Relevance: Even among accredited
      bariatric surgery centers, wide variation exists in rates of postoperative
      serious complications across geographic location and operative volumes. Given
      that a large proportion of centers are geographically located near higher
      performing centers, opportunities for improvement through regional collaboratives
      or selective referral should be considered.

PMID- 28445568
TI  - Balancing Motherhood, Career, and Medicine.

PMID- 28445569
TI  - Small-Bowel Obstruction in a 45-Year-Old Woman.

PMID- 28445570
TI  - Medical Marijuana Laws and Cannabis Use: Intersections of Health and Policy.

PMID- 28445571
TI  - Quality Improvement and Accreditation: The Never-Ending Story.

PMID- 28445572
TI  - Suggestions for Increasing Diversity in Clinical Trials.

PMID- 28445573
TI  - The Management of Antiplatelet and Antithrombotic Regimens in Patients With
      Mechanical Valves Undergoing Percutaneous Coronary Intervention: A Forgotten
      Cohort?

PMID- 28445574
TI  - Errors in Figure Panel Labels.

PMID- 28445575
TI  - A More Common Massive Retroperitoneal Mass.

PMID- 28445576
TI  - Enhancing the Relevance of Skin Self-examination for Latinos.

PMID- 28445577
TI  - Intensity of Statin Treatment and Mortality.

PMID- 28445579
TI  - Complete Response of Advanced Melanoma Treated With Talimogene Laherparepvec and
      Subsequent Sweet's-like Infiltrate.

PMID- 28445578
TI  - Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect
      on the Decision to Biopsy.
AB  - Importance: Expression of long intergenic non-protein coding RNA 518 (LINC00518)
      and preferentially expressed antigen in melanoma (PRAME) genes, obtained via
      noninvasive adhesive patch biopsy, is a sensitive and specific method for
      detection of cutaneous melanoma. However, the utility of this test in biopsy
      decisions made by dermatologists has not been evaluated. Objective: To determine
      the utility of the pigmented lesion assay (PLA) for LINC00518/PRAME expression in
      decisions to biopsy a series of pigmented skin lesions. Design, Setting, and
      Participants: In this secure web-based, multiple-reader-multiple-case study, 45
      board-certified dermatologists each evaluated 60 clinical and dermoscopic images
      of clinically atypical pigmented lesions, first without and then with PLA gene
      expression information and were asked whether the lesions should be biopsied.
      Data were collected from March 24, 2014, through November 13, 2015.
      Interventions: Participants were given a report for each lesion, which included
      the results of an assay for expression of LINC00518/PRAME and a PLA score with
      data on the predictive values of the information provided. Main Outcomes and
      Measures: Biopsy sensitivity and specificity with vs without PLA data. Results:
      Forty-five dermatologists (29 male and 16 female) performed the evaluation. After
      incorporating the PLA into their decision as to whether to biopsy a pigmented
      lesion suggestive of melanoma, dermatologists improved their mean biopsy
      sensitivity from 95.0% to 98.6% (P = .01); specificity increased from 32.1% to
      56.9% (P < .001) with PLA data. Conclusions and Relevance: The noninvasive PLA
      enables dermatologists to significantly improve biopsy specificity while
      maintaining or improving sensitivity. This result may increase the number of
      early melanomas biopsied and reduce the number of benign lesions biopsied,
      thereby improving patient outcomes and reducing health care costs.

PMID- 28445580
TI  - The Influence of Social Support and Coping on Quality of Life Among Elderly With
      Age-Related Hearing Loss.
AB  - Purpose: The consequences of hearing loss hinder the everyday life of older
      adults and are associated with reduced well-being. The research aim was to
      explore the influence of hearing problems, various coping strategies, and
      perceived social support on quality of life. Method: Sixty-five older adults with
      age-related hearing loss (>=55 years) in Austria participated and completed a
      paper-pencil survey with standardized questionnaires: Hearing Handicap Inventory
      for the Elderly (Ventry and Weinstein, 1982), Assessment for Coping and Stress
      (Laireiter, 1997), short form of the Social Support Questionnaire (Fydrich,
      Sommer, Tydecks, & Brahler, 2009), and World Health Organization Quality of Life
      Scale-Brief Version (World Health Organization, 1996). Results: Quality of life
      was predicted by perceived social support and the number of comorbid diseases
      (i.e., the physical, psychological, environmental, and social quality of life was
      better the greater the extent of perceived social support and poorer the more
      diseases from which the participants suffered). Conclusions: Perceived social
      support may be a relevant factor to focus on in auditory rehabilitation programs,
      in particular, for participants who communicate little support in hearing-related
      situations and are, hence, at a relative disadvantage. The involvement of
      significant others in counseling could facilitate the everyday life for older
      adults with age-related hearing loss and their significant others.

PMID- 28445581
TI  - Definition of "Close Margin" in Oral Cancer Surgery and Association of Margin
      Distance With Local Recurrence Rate.

PMID- 28445582
TI  - Single IRBs in Multisite Trials: Questions Posed by the New NIH Policy.

PMID- 28445583
TI  - A More Common Massive Retroperitoneal Mass-Reply.

PMID- 28445584
TI  - Chronic Opioid Use Following Surgery for Oral Cavity Cancer.

PMID- 28445586
TI  - Predictors of outcome among patients on extracorporeal membrane oxygenation as a
      bridge to lung transplantation.
AB  - BACKGROUND: There is a lack of data regarding clinical variables associated with
      successful bridge to lung transplantation (LT) using extracorporeal membrane
      oxygenation (ECMO) support. METHODS: We reviewed the institutional database for
      patients supported with veno-venous (VV) or veno-arterial ECMO as a bridge to LT
      (n=25; mean age: 50.6+/-14.2 years). We recorded clinical and laboratory
      variables, findings on echocardiogram and development of organ dysfunction along
      with hospital and one-year survival. Variables were compared between patients
      successfully bridged to LT versus those who were not. RESULTS: The most common
      diagnostic group was interstitial lung disease (18/25, 72%). VV-ECMO was used in
      the majority (84%). Fifteen patients (60%) were successfully bridged to LT, and
      the majority were alive at 1 year (14/15, 93.3%). The presence of right
      ventricular systolic dysfunction on pre-ECMO echocardiogram was associated with
      increased risk of unsuccessful bridging (OR, 95% CI: 2.67, 1.01-6.99, P=.041).
      While on ECMO, trough albumin levels <2.5 gm%, peak blood urea nitrogen levels
      >35 mg/dL and positive fluid balance were also associated with failure to bridge
      to LT. CONCLUSIONS: Among patients awaiting LT, the presence of RV systolic
      dysfunction before ECMO initiation along with worsening renal functions, low
      albumin levels, and volume overload is associated with poor outcomes.

PMID- 28445585
TI  - C-type starches and their derivatives: structure and function.
AB  - The C-type starches are widely distributed in seeds or rhizomes of various
      legumes, medicinal plants, and crops. These carbohydrate polymers directly affect
      the application of starchy plant resources. The structural and crystal properties
      of starches are crucial parameters of starch granules, which significantly
      influence their physicochemical and mechanical properties. The unique crystal
      structure consisting of both A- and B-type polymorphs endows C-type starches with
      specific crystal adjustability. Furthermore, large proportions of resistant
      starches and slowly digestible starches are C-type starches, which contribute to
      benign glycemic response and proliferation of gut microflora. Here, we review the
      distribution of C-type starches in various plant sources, the structural models
      and crystal properties of C-type starches, and the behavior and functionality
      relevant to modified C-type starches. We outline recent advances, potential
      applications, and limitations of C-type starches in industry, aiming to provide a
      theoretical basis for further research and to broaden the prospects of its
      applications.

PMID- 28445587
TI  - CB1 receptors down-regulate a cAMP/Epac2/PLC pathway to silence the nerve
      terminals of cerebellar granule cells.
AB  - Cannabinoid receptors mediate short-term retrograde inhibition of
      neurotransmitter release, as well as long-term depression of synaptic
      transmission at excitatory synapses. The responses of individual nerve terminals
      in VGLUT1-pHluorin transfected cerebellar granule cells to cannabinoids have
      shown that prolonged activation of cannabinoid type 1 receptors (CB1Rs) silences
      a subpopulation of previously active synaptic boutons. Adopting a combined
      pharmacological and genetic approach to study the molecular mechanisms of CB1R
      induced silencing, we found that adenylyl cyclase inhibition decreases cAMP
      levels while it increases the number of silent synaptic boutons and occludes the
      induction of further silencing by the cannabinoid agonist HU-210. Guanine
      nucleotide exchange proteins directly activated by cAMP (Epac proteins) mediate
      some of the presynaptic effects of cAMP in the potentiation of synaptic
      transmission. ESI05, a selective Epac2 inhibitor, and U-73122, the specific
      inhibitor of phospholipase C (PLC), both augment the number of silent synaptic
      boutons. Moreover, they abolish the capacity of the Epac activator, 8-(4
      chlorophenylthio)-2'-O-methyladenosine 3',5'-cyclic monophosphate monosodium
      hydrate, to prevent HU-210-induced silencing consistent with PLC signaling lying
      downstream of Epac2 proteins. Furthermore, Rab3-interacting molecule (RIM)1alpha
      KO cells have many more basally silent synaptic boutons (12.9 +/- 3.5%) than wild
      type cells (1.1 +/- 0.5%). HU-210 induced further silencing in these mutant
      cells, although 8-(4-chlorophenylthio)-2'-O-methyladenosine 3',5'-cyclic
      monophosphate monosodium hydrate only awoke the HU-210-induced silence and not
      the basally silent synaptic boutons. This behavior can be rescued by expressing
      RIM1alpha in RIM1alpha KO cells, these cells behaving very much like wild-type
      cells. These findings support the hypothesis that a cAMP/Epac/PLC signaling
      pathway targeting the release machinery appears to mediate cannabinoid-induced
      presynaptic silencing.

PMID- 28445588
TI  - The relative importance of pollinator abundance and species richness for the
      temporal variance of pollination services.
AB  - The relationship between biodiversity and the stability of ecosystem function is
      a fundamental question in community ecology, and hundreds of experiments have
      shown a positive relationship between species richness and the stability of
      ecosystem function. However, these experiments have rarely accounted for common
      ecological patterns, most notably skewed species abundance distributions and non
      random extinction risks, making it difficult to know whether experimental results
      can be scaled up to larger, less manipulated systems. In contrast with the
      prolific body of experimental research, few studies have examined how species
      richness affects the stability of ecosystem services at more realistic, landscape
      scales. The paucity of these studies is due in part to a lack of analytical
      methods that are suitable for the correlative structure of ecological data. A
      recently developed method, based on the Price equation from evolutionary biology,
      helps resolve this knowledge gap by partitioning the effect of biodiversity into
      three components: richness, composition, and abundance. Here, we build on
      previous work and present the first derivation of the Price equation suitable for
      analyzing temporal variance of ecosystem services. We applied our new derivation
      to understand the temporal variance of crop pollination services in two study
      systems (watermelon and blueberry) in the mid-Atlantic United States. In both
      systems, but especially in the watermelon system, the stronger driver of temporal
      variance of ecosystem services was fluctuations in the abundance of common bee
      species, which were present at nearly all sites regardless of species richness.
      In contrast, temporal variance of ecosystem services was less affected by
      differences in species richness, because lost and gained species were rare. Thus,
      the findings from our more realistic landscapes differ qualitatively from the
      findings of biodiversity-stability experiments.

PMID- 28445590
TI  - Long term radiographic findings of breast brachytherapy: Implications of surgical
      volume.
AB  - PURPOSE: Little is known about long-term radiographic findings after treatment
      with accelerated partial breast irradiation (APBI). METHODS: Univariate and
      multivariate analysis of factors leading to formation and resolution of seroma
      were performed in patients treated with lumpectomy and APBI. RESULTS: Post
      treatment images of 129 patients were reviewed by one radiologist. Median
      surgical excision volume was 108.9 cc (range 20.5-681.9). Primary mode of imaging
      was mammogram. Median time from end of RT to first and last surveillance image
      was 6 and 54 months, respectively. Median number of images was 7 (range 3-12).
      Seroma was identified in 98 (76%) patients, with median maximum diameter of 3.9
      cm. Forty (41%) patients experienced resolution of seroma, at a median time of 29
      months (range 6-74). On univariate analysis, surgical excision volume was
      associated with seroma formation, and tumor stage and margin re-excision were
      significant on univariate and multivariate analysis. No factors were associated
      with seroma resolution. CONCLUSION: Seroma formation after APBI resolves around
      2.5 years for many patients, but persists for others possibly due to primary
      tumor and surgical excision volumes. With revised criteria on the definition of
      positive margins, smaller volumes may lead to decreased risk of seroma formation
      for future patients.

PMID- 28445591
TI  - Screening endoscopy finds high prevalence of Helicobacter pylori and intestinal
      metaplasia in Korean American with limited access to health care.
AB  - BACKGROUND: Gastric cancer (GC) is the leading cause of cancer death among Korean
      Americans. Prevention and early detection is improved by screening. METHODS:
      Between September 2013 and March 2015, ethnic Koreans age 40 or older without
      history or symptoms of GC and without upper endoscopy (UE) during previous 3
      years were enrolled. Participants were offered screening with GC risk assessment
      followed by UE with biopsies. RESULTS: Risk assessment was provided to 146
      participants (age 55.6 +/- 8.3 years; 52.1% female; 92.5% uninsured), of whom 99
      (67.8%) returned for UE. Undergoing UE was independently associated with family
      history of GC (OR 12.33, 95% CI:1.52-100.17), being a former smoker (6.68,1.42
      31.32), and Hp-negative status (0.25,0.11-0.57). Among UE recipients, half
      (49.5%) had intestinal metaplasia (IM) only (n = 24), Hp only (n = 12), or both
      (n = 13). No case of GC was found. Adjusted for age, IM was independently
      associated with male sex (2.89,1.12-7.42), current Hp (2.90,0.99-8.51), unmarried
      status (single or divorced) (4.23,1.23-14.56). CONCLUSIONS: High prevalence of
      risk factors associated with gastric carcinogenesis including Hp infection and IM
      exists in Korean Americans who underwent upper endoscopic screening. Acceptance
      of GC screening is informed by personal risk factors. These findings support the
      need to improve access to screening UE among KAs.

PMID- 28445589
TI  - A network engineering perspective on probing and perturbing cognition with
      neurofeedback.
AB  - Network science and engineering provide a flexible and generalizable tool set to
      describe and manipulate complex systems characterized by heterogeneous
      interaction patterns among component parts. While classically applied to social
      systems, these tools have recently proven to be particularly useful in the study
      of the brain. In this review, we describe the nascent use of these tools to
      understand human cognition, and we discuss their utility in informing the
      meaningful and predictable perturbation of cognition in combination with the
      emerging capabilities of neurofeedback. To blend these disparate strands of
      research, we build on emerging conceptualizations of how the brain functions (as
      a complex network) and how we can develop and target interventions or modulations
      (as a form of network control). We close with an outline of current frontiers
      that bridge neurofeedback, connectomics, and network control theory to better
      understand human cognition.

PMID- 28445592
TI  - Polo-like-kinase 1 is a proviral host factor for hepatitis B virus replication.
AB  - : Chronic hepatitis B virus (HBV) infection is a major risk factor for
      hepatocellular carcinoma (HCC) and current treatments for chronic hepatitis B and
      HCC are suboptimal. Herein, we identified cellular serine/threonine Polo-like
      kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study
      was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate
      PLK1 inhibition a potential antiviral strategy. To this end, we employed
      physiologically relevant HBV infection models of primary human hepatocytes (PHHs)
      and differentiated HepaRG cells in conjunction with pharmacologic PLK1
      inhibitors, small interfering RNA (siRNA)-mediated knockdown, and overexpression
      of constitutively active PLK1 (PLK1CA ). In addition, a humanized liver Fah-/-
      /Rag2-/- /Il2rg-/- (FRG) mouse model was used to determine the antiviral effect
      of PLK1 inhibitor BI-2536 on HBV infection in vivo. Finally, in vitro PLK1 kinase
      assays and site-directed mutagenesis were employed to demonstrate that HBV core
      protein (HBc) is a PLK1 substrate. We demonstrated that HBV infection activated
      cellular PLK1 in PHHs and differentiated HepaRG cells. PLK1 inhibition by BI-2536
      or siRNA-mediated knockdown suppressed HBV DNA biosynthesis, whereas
      overexpression of PLK1CA increased it, suggesting that the PLK1 effects on viral
      biosynthesis are specific and that PLK1 is a proviral cellular factor.
      Significantly, BI-2536 administration to HBV-infected humanized liver FRG mice
      strongly inhibited HBV infection, validating PLK1 as an antiviral target in vivo.
      The proviral action of PLK1 is associated with the biogenesis of the
      nucleocapsid, as BI-2536 leads to its decreased intracellular
      formation/accumulation. In this respect, our studies identified HBc as a PLK1
      substrate in vitro, and mapped PLK1 phosphorylation sites on this protein.
      CONCLUSION: PLK1 is a proviral host factor that could be envisaged as a target
      for combined antiviral and antitumoral strategies against HBV infection and HBV
      mediated carcinogenesis. (Hepatology 2017;66:1750-1765).

PMID- 28445594
TI  - Porcine milk induces a strengthening of barrier function in porcine jejunal
      epithelium in vitro.
AB  - Milk contains a variety of components that have been shown to affect the
      expression and localization of epithelial tight junction proteins and therefore
      the intestinal barrier. Thus, we hypothesized that milk would have an effect on
      intestinal barrier properties, owing to effects on the tight junction in an
      intraspecies porcine intestinal in vitro model. Jejunal samples of piglets
      derived from different age groups were analyzed. Transepithelial electrical
      resistance was recorded employing the Ussing chamber technique. Porcine milk or
      predigested milk in buffer solution was added to the apical side, and effects
      were compared to untreated controls. Unidirectional paracellular flux
      measurements were performed using sodium fluorescein. Tight junction protein
      expression and localization were analyzed by immunoblotting and
      immunofluorescence microscopy. Incubation with milk or predigested milk led to an
      increase in transepithelial electrical resistance, while paracellular
      permeability for sodium fluorescein did not result in significant changes.
      Densitometric analysis of immunoblot signals did not show significant alterations
      in claudin expression, but a reduction of claudin signals in apicolateral
      membrane compartments in both approaches became apparent via immunohistology. The
      functional effect might reflect a physiological protective mechanism, when
      offspring exclusively rely on their mother's milk and are exposed to a plethora
      of potentially barrier-perturbing factors.

PMID- 28445593
TI  - NR5A2 discovering compounds that block tumor growth in PDAC.
AB  - Pancreatic cancers depend on driver molecules, oncogene proteins such as RAS.
      NR5A2 protein is a transcription factor and either activates or inhibits
      transcription through actions at hundreds of enhancers. It has unusual properties
      with effects appearing in multiple signaling networks. NR5A2 is a pluripotency
      reprogramming factor in the class nuclear receptor. Its controlling hormone is
      PIP3. Experiments suggest NR5A2 activation drives PDAC and inhibitors blunt
      cancer cell proliferation.

PMID- 28445595
TI  - Ventricular fibrillation cardiac arrest produces a chronic striatal
      hyperdopaminergic state that is worsened by methylphenidate treatment.
AB  - Cardiac arrest survival rates have improved with modern resuscitation techniques,
      but many survivors experience impairments associated with hypoxic-ischemic brain
      injury (HIBI). Currently, little is understood about chronic changes in striatal
      dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA
      enhancing agents in neurorehabilitation, investigation evaluating dopaminergic
      alterations after cardiac arrest (CA) is necessary to optimize rehabilitation
      approaches. We hypothesized that striatal DA neurotransmission would be altered
      chronically after ventricular fibrillation cardiac arrest (VF-CA). Fast-scan
      cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical
      stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA
      neurotransmission in the dorsal striatum (D-Str) and nucleus accumbens 14 days
      after a 5-min VF-CA when compared to Sham or Naive. VF-CA increased D-Str-evoked
      overflow [DA], total [DA] released, and initial DA release rate versus controls,
      despite also increasing maximal velocity of DA reuptake (Vmax ). Methylphenidate
      (10 mg/kg), a DA transporter inhibitor, was administered to VF-CA and Shams after
      establishing a baseline, pre-drug 60 Hz, 5 s stimulation response.
      Methylphenidate increased initial evoked overflow [DA] more-so in VF-CA versus
      Sham and reduced D-Str Vmax in VF-CA but not Shams; these findings are consistent
      with upregulated striatal DA transporter in VF-CA versus Sham. Our work
      demonstrates that 5-min VF-CA increases electrically stimulated DA release with
      concomitant upregulation of DA reuptake 2 weeks after brief VF-CA insult. Future
      work should elucidate how CA insult duration, time after insult, and insult type
      influence striatal DA neurotransmission and related cognitive and motor
      functions.

PMID- 28445596
TI  - Effectiveness, safety, and acceptability of first-trimester medical termination
      of pregnancy performed by non-doctor providers: a systematic review.
AB  - BACKGROUND: Previous systematic reviews have concluded that medical termination
      of pregnancy (TOP) performed by non-doctor providers may be as effective and safe
      as when provided by doctors. Medical treatment of incomplete miscarriage by non
      doctor providers and the treated women's acceptance of non-doctor providers of
      TOP has not previously been reviewed. OBJECTIVES: To review the effectiveness,
      safety, and acceptability of first-trimester medical TOP, including medical
      treatment for incomplete miscarriage, by trained non-doctor providers. SEARCH
      STRATEGY AND SELECTION CRITERIA: A search strategy using appropriate medical
      subject headings was developed. Electronic databases (PubMed, Popline, Cochrane,
      CINAHL, Embase, and ClinicalTrials.gov) were searched from inception through
      April 2016. Randomised controlled trials and comparative observational studies
      were included. DATA COLLECTION AND ANALYSIS: Meta-analyses were performed for
      included randomised controlled trials regarding the outcomes of effectiveness and
      acceptability to women. Certainty of evidence was established using the GRADE
      approach assessing study limitations, consistency of effect, imprecision,
      indirectness and publication bias. MAIN RESULTS: Six papers were included.
      Medical TOP and medical treatment of incomplete miscarriage is probably equally
      effective when performed by non-doctor providers as when performed by doctors (RR
      1.00; 95% CI 0.99-1.01). Women's acceptance, reported as overall satisfaction
      with the allocated provider, is probably equally high between groups (RR 1.00;
      95% CI 1.00-1.01). CONCLUSION: Medical TOP and medical treatment of incomplete
      miscarriage provided by trained non-doctor providers is probably equally as
      effective and acceptable to women as when provided by doctors. TWEETABLE
      ABSTRACT: Medical termination of pregnancy performed by doctors and non-doctors
      can be equally effective and acceptable.

PMID- 28445598
TI  - Dabigatran enhances platelet reactivity and platelet thrombin receptor expression
      in patients with atrial fibrillation: reply.

PMID- 28445597
TI  - Taller height as a risk factor for venous thromboembolism: a Mendelian
      randomization meta-analysis.
AB  - : Essentials Observational data suggest taller people have a higher risk of
      venous thromboembolism (VTE). We used Mendelian randomization techniques to
      further explore this association in three studies. Risk of VTE increased by 30
      40% for each 10 cm increment in height. Height was more strongly associated with
      deep vein thrombosis than with pulmonary embolism. SUMMARY: Background Taller
      height is associated with a greater risk of venous thromboembolism (VTE).
      Objectives To use instrumental variable (IV) techniques (Mendelian randomization)
      to further explore this relationship. Methods Participants of European ancestry
      were included from two cohort studies (Atherosclerosis Risk in Communities [ARIC]
      study and Cardiovascular Health Study [CHS]) and one case-control study (Mayo
      Clinic VTE Study [Mayo]). We created two weighted genetic risk scores (GRSs) for
      height; the full GRS included 668 single-nucleotide polymorphisms (SNPs) from a
      previously published meta-analysis, and the restricted GRS included a subset of
      362 SNPs not associated with weight independently of height. Standard logistic
      regression and IV models were used to estimate odds ratios (ORs) for VTE per 10
      cm increment in height. ORs were pooled across the three studies by the use of
      inverse variance-weighted random effects meta-analysis. Results Among 9143 ARIC
      and 3180 CHS participants free of VTE at baseline, there were 367 and 109
      incident VTE events. There were 1143 VTE cases and 1292 controls included from
      Mayo. The pooled ORs from non-IV models and models using the full and restricted
      GRSs as IVs were 1.27 (95% confidence interval [CI] 1.11-1.46), 1.34 (95% CI 1.04
      1.73) and 1.45 (95% CI 1.04-2.01) per 10-cm greater height, respectively.
      Conclusions Taller height is associated with an increased risk of VTE in adults
      of European ancestry. Possible explanations for this association, including
      taller people having a greater venous surface area, a higher number of venous
      valves, or greater hydrostatic pressure, need to be explored further.

PMID- 28445599
TI  - Growth engineering of Synechococcus elongatus PCC 7942 for mixotrophy under
      natural light conditions for improved feedstock production.
AB  - Synechococcus elongatus PCC 7942 has been widely explored as cyanobacterial cell
      factory through genetic modifications for production of various value-added
      compounds. However, successful industrial scale-ups have not been reported for
      the system predominantly due to its obligate photoautotrophic metabolism and use
      of artificial light in photobioreactors. Hence, engineering the organism to
      perform mixotrophy under natural light could serve as an effective solution.
      Thus, we applied a genetically engineered strain of Synechococcus elongatus PCC
      7942 expressing heterologous hexose transporter gene (galP) to perform mixotrophy
      under natural light in a temperature controlled environmental chamber (EC). We
      systematically studied the comparative performances of these transformants using
      autotrophy and mixotrophy, which showed 3.4 times increase in biomass
      productivity of mixotrophically grown transformants over autotrophs in EC.
      Chlorophyll a yield was found to have decreased in mixotrophic conditions,
      possibly indicating reduced dependency on light for energy metabolism. Although
      pigment yield decreases under mixotrophy, titer was found to have improved due to
      increased biomass productivity. Carotenoid analysis showed that zeaxanthin is the
      major carotenoid produced by the species which is essential for photoprotection.
      Our work thus demonstrates that mixotrophy under temperature controlled natural
      light can serve as the viable solution to improve biomass productivity of
      Synechococcus elongatus PCC 7942 and for commercial production of natural or
      engineered value added compounds from the system. (c) 2017 American Institute of
      Chemical Engineers Biotechnol. Prog., 33:1182-1192, 2017.

PMID- 28445600
TI  - Caplacizumab reduces the frequency of major thromboembolic events, exacerbations
      and death in patients with acquired thrombotic thrombocytopenic purpura.
AB  - : Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with
      significant morbidity/mortality. Caplacizumab's effect on major thromboembolic
      (TE) events, exacerbations and death was studied. Fewer caplacizumab-treated
      patients had a major TE event, an exacerbation, or died versus placebo.
      Caplacizumab has the potential to reduce the acute morbidity and mortality
      associated with aTTP. SUMMARY: Background Acquired thrombotic thrombocytopenic
      purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In
      spite of treatment with plasma exchange and immunosuppression, patients remain at
      risk for thrombotic complications, exacerbations, and death. In the phase II
      TITAN study, treatment with caplacizumab, an anti-von Willebrand factor
      Nanobody(r) was shown to reduce the time to confirmed platelet count
      normalization and exacerbations during treatment. Objective The clinical benefit
      of caplacizumab was further investigated in a post hoc analysis of the incidence
      of major thromboembolic events and exacerbations during the study drug treatment
      period and thrombotic thrombocytopenic purpura-related death during the study.
      Methods The Standardized Medical Dictionary for Regulatory Activities (MedDRA)
      Query (SMQ) for 'embolic and thrombotic events' was run to investigate the
      occurrence of major thromboembolic events and exacerbations in the safety
      population of the TITAN study, which consisted of 72 patients, of whom 35
      received caplacizumab and 37 received placebo. Results Four events (one pulmonary
      embolism and three aTTP exacerbations) were reported in four patients in the
      caplacizumab group, and 20 such events were reported in 14 patients in the
      placebo group (two acute myocardial infarctions, one ischemic stroke, one
      hemorrhagic stroke, one pulmonary embolism, one deep vein thrombosis, one venous
      thrombosis, and 13 aTTP exacerbations). Two of the placebo-treated patients died
      from aTTP during the study. Conclusion In total, 11.4% of caplacizumab-treated
      patients and 43.2% of placebo-treated patients experienced one or more major
      thromboembolic events, experienced an exacerbation, or died. This analysis shows
      the potential for caplacizumab to reduce the risk of major thromboembolic
      morbidities and mortality associated with aTTP.

PMID- 28445602
TI  - Identification of a novel miRNA that increases transient protein expression in
      combination with valproic acid.
AB  - Transient gene expression in mammalian cells is an efficient process to produce
      recombinant proteins for various research applications and large molecule
      therapeutics development. For the first time, we report a screen to identify
      human microRNAs (miRNAs) that increase titers after polyethylenimine (PEI)
      mediated transient transfection of a HEK293 cell line. From a library of 875
      miRNAs, we identified 2 miRNAs, miR-26a-5p and miR-337-5p, that increased human
      IgG1 (huIgG1) yields by 50 and 25%, respectively. The titer increase was
      achievable by expressing miR-26a-5p from oligonucleotides or a plasmid.
      Furthermore, combining miR-26a-5p with valproic acid (VPA) treatment doubled
      huIgG1 titers. Assessment of miR-26a-5p and VPA treatment across a panel of 32
      human and murine antibodies demonstrates that the level of yield enhancement was
      molecule-dependent, with most exhibiting a range of 50-100% titer increase. These
      findings exemplify that combining genetic and chemical manipulation can be an
      effective strategy to enhance transient transfection productivity. (c) 2017
      American Institute of Chemical Engineers Biotechnol. Prog., 33:1139-1145, 2017.

PMID- 28445601
TI  - Status epilepticus in dogs and cats, part 2: treatment, monitoring, and
      prognosis.
AB  - OBJECTIVE: To discuss current anticonvulsant drug options and advances in
      treatment of status epilepticus (SE) and to review the prognosis associated with
      SE. TREATMENT: When treating a patient with SE, the main goals are to halt
      seizure activity, prevent further seizures, identify the cause of the seizures,
      and manage any complications. The veterinary literature indicates that
      benzodiazepines are the most common class of drugs used for the initial treatment
      of SE. Although many anticonvulsant drugs are currently available for treatment
      of SE, there is a lack of evidence demonstrating clear benefit to the use of
      specific therapeutics for benzodiazepine-refractory SE. Several multicenter,
      randomized, and placebo-controlled clinical trials are currently investigating
      the efficacy of new drugs, such as fosphenytoin, for use in canine SE. Another
      active area of research is the investigation of nonpharmacologic methods of
      seizure treatment including percutaneous vagal nerve stimulation and transcranial
      ultrasonic neuromodulation. MONITORING: Electroencephalography (EEG) is
      underutilized in the management of veterinary seizure disorders. However, recent
      advances in EEG technology may allow for earlier and proactive therapeutic
      interventions in epileptic patients, provide objective data collection regarding
      treatment efficacy, and yield insight into the neurologic status of patients with
      SE. Most importantly, use of EEG in patients with SE will lead to increased
      recognition of nonconvulsive seizures and nonconvulsive SE. PROGNOSIS: Mortality
      associated with SE is as high as 25% in dogs due to direct and indirect causes of
      death. Dogs with seizure disorders have a decreased lifespan compared to the
      general population, and epileptic dogs with SE have a significantly abbreviated
      lifespan compared to epileptics that do not experience SE. In people,
      nonconvulsive SE has a higher morbidity and mortality than convulsive SE,
      regardless of patient age or underlying diagnosis.

PMID- 28445603
TI  - Alternating flow filtration as an alternative to internal spin filter based
      perfusion process: Impact on productivity and product quality.
AB  - This article reports the results obtained from comparison of internal spin filter
      (ISF) and alternating flow filtration (ATF) as cell retention systems, regarding
      cell growth, volumetric perfusion rate, cell specific perfusion rate and cell
      productivity in the fermentation process. As expected we were able to reach
      higher cell densities and to achieve longer runs since ATF systems are known to
      be less affected by fouling. Volumetric production of the reactor using the ATF
      system was 50-70% higher than the production achieved using the ISF due to higher
      cell density and a two-fold increase in the perfusion rate. On the other hand,
      downstream processing performances were evaluated regarding chromatographic steps
      yields and productivity and quality attributes of the purified materials. Similar
      results were obtained for all evaluated systems. The fact that we were able to
      achieve a 2 working volumes (WV)/day perfusion rate using an ATF system as cell
      retention device allowed us to virtually double the WV of a 25 L reactor. These
      results constitute valuable data for the optimization of recombinant protein
      production in perfusion processes since a two-fold increase in the average
      production of a manufacturing facility could be easily achieved as long as
      downstream scale up is possible. (c) 2017 American Institute of Chemical
      Engineers Biotechnol. Prog., 33:1010-1014, 2017.

PMID- 28445604
TI  - Investigating the effect of fibulin-1 on the differentiation of human nasal
      inferior turbinate-derived mesenchymal stem cells into osteoblasts.
AB  - Many extracellular matrix proteins have positive influences on the adhesion,
      proliferation, and differentiation of stem cells into specific cell linages.
      Fibulin-1 (FBLN1), a member of a growing family of extracellular glycoproteins,
      contributes to the structure of the extracellular matrix. Here, we investigated
      the effect of FBLN1 on the ability of human nasal inferior turbinate-derived
      mesenchymal stem cells (hTMSCs) to undergo osteogenic differentiation. After we
      generated recombinant FBLN1, the characteristics of FBLN1-treated hTMSCs were
      evaluated using MTT assay, ALP and mineralization activities, and quantitative
      real-time PCR. FBLN1 significantly enhanced the adhesion activity (p < 0.001) and
      proliferation of hTMSCs (p < 0.05). The ALP and mineralization activities of
      cells were dramatically increased (p < 0.01) after 9 and 12 days of FBLN1
      treatment, respectively. This indicated the ability of FBLN1 to induce hTMSCs to
      differentiate into osteoblasts. Furthermore, increasing the mRNA levels of
      osteogenic marker genes, such as a transcriptional coactivator with a PDZ-binding
      motif (TAZ), alkaline phosphatase (ALP), collagen type I (Col I), and osteocalcin
      (OCN), improved bone repair and regeneration. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 105A: 2291-2298, 2017.

PMID- 28445606
TI  - Structural and biological properties of thermosensitive chitosan-graphene hybrid
      hydrogels for sustained drug delivery applications.
AB  - Chitosan has the ability to make injectable thermosensitive hydrogels which has
      been highly investigated for drug delivery applications. The addition of
      nanoparticles is one way to increase the mechanical strength of thermosensitive
      chitosan hydrogel and subsequently and control the burst release of drug.
      Graphene nanoparticles have shown unique mechanical, optical and electrical
      properties which can be exploited for biomedical applications, especially in drug
      delivery. This study, have focused on the mechanical properties of a
      thermosensitive and injectable hybrid chitosan hydrogel incorporated with
      graphene nanoparticles. Scanning electron microscope (SEM), Fourier transform
      infrared (FTIR) spectroscopy, Raman spectroscopy, and X-ray diffraction (XRD)
      have been used for morphological and chemical characterization of graphene
      infused chitosan hydrogels. The cell viability and cytotoxicity of graphene
      contained hydrogels were analyzed using the alamarBlue(r) technique. In-vitro
      methotrexate (MTX) release was investigated from MTX-loaded hybrid hydrogels as
      well. As a last step, to evaluate their efficiency as a cancer treatment delivery
      system, an in vitro anti-tumor test was also carried out using MCF-7 breast
      cancer cell lines. Results confirmed that a thermosensitive chitosan-graphene
      hybrid hydrogel can be used as a potential breast cancer therapy system for
      controlled delivery of methotrexate. (c) 2017 Wiley Periodicals, Inc. J Biomed
      Mater Res Part A: 105A: 2381-2390, 2017.

PMID- 28445607
TI  - Fractal characteristics of the microvascular network: A useful index to assess
      vascularization level of porous silk fibroin biomaterial.
AB  - The neovascularization of biomaterials for tissue engineering is not only related
      to growth of capillaries but also involves appropriate hierarchy distribution of
      the microvessels. In this study, we proposed hierarchy distribution contrast
      method which can assess vascular transport capacity, in order to examine the
      hierarchy distribution of the neovessels during vascularization of the porous
      silk fibroin biomaterials implanted into rats and its evolution. The results
      showed that the fractal characteristics appeared toward the end of the
      vascularization stages, and the structure of the microvascular network after 3
      weeks of implantation was similar to the fractal microvascular tree with
      bifurcation exponent x = 3 and fractal dimension D = 1.46, which became a sign of
      maturation of the regenerative vasculature. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 105A: 2276-2290, 2017.

PMID- 28445605
TI  - High-throughput cell mechanical phenotyping for label-free titration assays of
      cytoskeletal modifications.
AB  - The mechanical fingerprint of cells is inherently linked to the structure of the
      cytoskeleton and can serve as a label-free marker for cell homeostasis or
      pathologic states. How cytoskeletal composition affects the physical response of
      cells to external loads has been intensively studied with a spectrum of
      techniques, yet quantitative and statistically powerful investigations in the
      form of titration assays are hampered by the low throughput of most available
      methods. In this study, we employ real-time deformability cytometry (RT-DC), a
      novel microfluidic tool to examine the effects of biochemically modified F-actin
      and microtubule stability and nuclear chromatin structure on cell deformation in
      a human leukemia cell line (HL60). The high throughput of our method facilitates
      extensive titration assays that allow for significance assessment of the observed
      effects and extraction of half-maximal concentrations for most of the applied
      reagents. We quantitatively show that integrity of the F-actin cortex and
      microtubule network dominate cell deformation on millisecond timescales probed
      with RT-DC. Drug-induced alterations in the nuclear chromatin structure were not
      found to consistently affect cell deformation. The sensitivity of the high
      throughput cell mechanical measurements to the cytoskeletal modifications we
      present in this study opens up new possibilities for label-free dose-response
      assays of cytoskeletal modifications.

PMID- 28445608
TI  - Sexual and Gender Minority Adolescents' Views On HIV Research Participation and
      Parental Permission: A Mixed-Methods Study.
AB  - CONTEXT: Sexual and gender minority adolescents are underrepresented in HIV
      research, partly because institutional review boards (IRBs) are reluctant to
      waive parental permission requirements for these studies. Understanding
      teenagers' perspectives on parental permission and the risks and benefits of
      participating in HIV research is critical to informing evidence-based IRB
      decisions. METHODS: Data from 74 sexual and gender minority adolescents aged 14
      17 who participated in an online focus group in 2015 were used to examine
      perspectives on the risks and benefits of participation in a hypothetical HIV
      surveillance study and the need for parental permission and adequate protections.
      Data were analyzed thematically; mixed methods analyses examined whether concerns
      about parental permission differed by whether teenagers were out to their
      parents. RESULTS: Most adolescents, especially those who were not out to their
      parents, would be unwilling to participate in an HIV study if parental permission
      were required. Perceived benefits of participation included overcoming barriers
      to HIV testing and contributing to the health of sexual and gender minority
      youth. Few risks of participation were identified. Adolescents suggested steps
      that researchers could take to facilitate informed decision making about research
      participation and ensure minors' safety in the absence of parental permission;
      these included incorporating multimedia presentations into the consent process
      and explaining researchers' motivations for conducting the study. CONCLUSIONS:
      Respondents believed that the benefits of HIV surveillance research outweighed
      the risks. Requiring parental permission may exclude many sexual and gender
      minority teenagers from taking part in HIV research, especially if they are not
      out.

PMID- 28445609
TI  - Exosomes derived from mesenchymal non-small cell lung cancer cells promote
      chemoresistance.
AB  - Non-small cell lung cancer (NSCLC) is the most common lung cancer type and the
      most common cause of mortality in lung cancer patients. NSCLC is often associated
      with resistance to chemotherapeutics and together with rapid metastatic spread,
      results in limited treatment options and poor patient survival. NSCLCs are
      heterogeneous, and consist of epithelial and mesenchymal NSCLC cells. Mesenchymal
      NSCLC cells are thought to be responsible for the chemoresistance phenotype, but
      if and how this phenotype can be transferred to other NSCLC cells is currently
      not known. We hypothesised that small extracellular vesicles, exosomes, secreted
      by mesenchymal NSCLC cells could potentially transfer the chemoresistance
      phenotype to surrounding epithelial NSCLC cells. To explore this possibility, we
      used a unique human bronchial epithelial cell (HBEC) model in which the parental
      cells were transformed from an epithelial to mesenchymal phenotype by introducing
      oncogenic alterations common in NSCLC. We found that exosomes derived from the
      oncogenically transformed, mesenchymal HBECs could transfer chemoresistance to
      the parental, epithelial HBECs and increase ZEB1 mRNA, a master EMT transcription
      factor, in the recipient cells. Additionally, we demonstrate that exosomes from
      mesenchymal, but not epithelial HBECs contain the ZEB1 mRNA, thereby providing a
      potential mechanism for the induction of a mesenchymal phenotype in recipient
      cells. Together, this work demonstrates for the first time that exosomes derived
      from mesenchymal, oncogenically transformed lung cells can transfer
      chemoresistance and mesenchymal phenotypes to recipient cells, likely via the
      transfer of ZEB1 mRNA in exosomes.

PMID- 28445610
TI  - Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer.
AB  - Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with
      a longer half-life (t1/2 ), higher plasma total irinotecan (tIRI), and lower SN
      38 maximum concentration (Cmax ) compared with nonliposomal irinotecan.
      Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and
      total SN-38 (tSN38) using patient samples from six studies. PK-safety association
      was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy
      association was evaluated from a phase III study in pancreatic cancer NAPOLI1.
      Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38)
      above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was
      associated with uSN38 Cmax and diarrhea with tIRI Cmax . Baseline predictive
      factors were race, body surface area, and bilirubin. Analysis identified PK
      factors associated with efficacy, safety, and predictive baseline factors. The
      results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to
      80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W.

PMID- 28445611
TI  - Equivalence of complex drug products: advances in and challenges for current
      regulatory frameworks.
AB  - Biotechnology and nanotechnology provide a growing number of innovator-driven
      complex drug products and their copy versions. Biologics exemplify one category
      of complex drugs, but there are also nonbiological complex drug products,
      including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying
      liposomes or emulsions, and glatiramoids. In this white paper, which stems from a
      1-day conference at the New York Academy of Sciences, we discuss regulatory
      frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the
      European Medicines Agency, the World Health Organization) to approve these
      complex drug products and their follow-on versions. One of the key questions
      remains how to assess equivalence of these complex products. We identify a number
      of points for which consensus was found among the stakeholders who were present:
      scientists from innovator and generic/follow-on companies, academia, and
      regulatory bodies from different parts of the world. A number of topics requiring
      follow-up were identified: (1) assessment of critical attributes to establish
      equivalence for follow-on versions, (2) the need to publish scientific findings
      in the public domain to further progress in the field, (3) the necessity to
      develop worldwide consensus regarding nomenclature and labeling of these complex
      products, and (4) regulatory actions when substandard complex drug products are
      identified.

PMID- 28445612
TI  - Influence of adjuvant formulation on inducing immune response in mice immunized
      with a recombinant serpin from Trichinella spiralis.
AB  - Nematodes of the genus Trichinella are one of the most widespread zoonotic
      pathogens on the world, and they can still cause major public health problems in
      many parts of the world. Vaccination against the helminth nematode Trichinella
      could be a good strategy to reduce the risk of human and animal infection. It was
      our aim to evaluate three adjuvants, which could be used as an efficient vaccine
      for animals in combination with rTs-Serpin antigen. In this study, BALB/c mice
      were vaccinated by an intramuscular route with rTs-Serpin antigen from the
      parasite Trichinella spiralis in combination with three different adjuvant
      formulations: Montanide ISA201, Montanide IMS 1313 N PR VG and Freund's complete
      adjuvant/Freund's incomplete adjuvant (FCA/FIA). The dynamics of IgG, IgM, IgE
      and cytokine production from spleen cells and worm reduction rate of the
      vaccinated mice were analysed. The results showed that rTs-serpin can induce
      partial protection against Trichinella larvae challenge in mice, when compared to
      the FCA-/FIA-formulated vaccination, the IMS1313 plus rTs-serpin mixture showed
      higher humoral immunity and similar levels of cellular immunity and worm
      reduction rate. The study suggested that Montanide IMS nanoparticles 1313 are as
      effective as FCA but less toxic; thus, Montanide IMS nanoparticles 1313 can be
      used as a good candidate of adjuvant for developing vaccine against Trichinella
      spiralis.

PMID- 28445613
TI  - Neuronal distribution of tyramine and the tyramine receptor AmTAR1 in the
      honeybee brain.
AB  - Tyramine is an important neurotransmitter, neuromodulator, and neurohormone in
      insects. In honeybees, it is assumed to have functions in modulating sensory
      responsiveness and controlling motor behavior. Tyramine can bind to two
      characterized receptors in honeybees, both of which are coupled to intracellular
      cAMP pathways. How tyramine acts on neuronal, cellular and circuit levels is
      unclear. We investigated the spatial brain expression of the tyramine receptor
      AmTAR1 using a specific antibody. This antibody detects a membrane protein of the
      expected molecular weight in western blot analysis. In honeybee brains, it labels
      different structures which process sensory information. Labeling along the
      antennal nerve, in projections of the dorsal lobe and in the gnathal ganglion
      suggest that tyramine receptors are involved in modulating gustatory and tactile
      perception. Furthermore, the ellipsoid body of the central complex and giant
      synapses in the lateral complex show AmTAR1-like immunoreactivity (AmTAR1-IR),
      suggesting a role of this receptor in modulating sky-compass information and/or
      higher sensor-motor control. Additionally, intense signals derive from the
      mushroom bodies, higher-order integration centers for olfactory, visual,
      gustatory and tactile information. To investigate whether AmTAR1-expressing brain
      structures are in vicinity to tyramine releasing sites, a specific tyramine
      antibody was applied. Tyramine-like labeling was observed in AmTAR1-IR positive
      structures, although it was sometimes weak and we did not always find a direct
      match of ligand and receptor. Moreover, tyramine-like immunoreactivity was also
      found in brain regions without AmTAR1-IR (optic lobes, antennal lobes),
      indicating that other tyramine-specific receptors may be expressed there.

PMID- 28445615
TI  - Status epilepticus in dogs and cats, part 1: etiopathogenesis, epidemiology, and
      diagnosis.
AB  - OBJECTIVE: To review current knowledge of the etiopathogenesis, diagnosis, and
      consequences of status epilepticus (SE) in veterinary patients. DATA SOURCES:
      Human and veterinary literature, including clinical and laboratory research and
      reviews. ETIOPATHOGENESIS: Status epilepticus is a common emergency in dogs and
      cats, and may be the first manifestation of a seizure disorder. It results from
      the failure of termination of an isolated seizure. Multiple factors are involved
      in SE, including initiation and maintenance of neuronal excitability, neuronal
      network synchronization, and brain microenvironmental contributions to
      ictogenesis. Underlying etiologies of epilepsy and SE in dogs and cats are
      generally classified as genetic (idiopathic), structural-metabolic, or unknown.
      DIAGNOSIS: Diagnosis of convulsive SE is usually made based on historical
      information and the nature of the seizures. Patient specific variables, such as
      the history, age of seizure onset, and physical and interictal neurological
      examination findings can help hone the rule out list, and are used to guide
      selection and prioritization of diagnostic tests. Electroencephalographic
      monitoring is routinely used in people to diagnose SE and guide patient care
      decisions, but is infrequently performed in veterinary medicine. Nonconvulsive
      status epilepticus has been recognized in veterinary patients; routine
      electroencephalography would aid in the diagnosis of this phenomenon in dogs and
      cats. CLINICAL SEQUELAE: Status epilepticus is a medical emergency that can
      result in life-threatening complications involving the brain and systemic organs.
      Status epilepticus often requires comprehensive diagnostic testing, treatment
      with multiple anticonvulsant agents, and intensive supportive care.

PMID- 28445616
TI  - Extract of Syzygium aromaticum suppress eEF1A protein expression and fungal
      growth.
AB  - AIMS: Clove extract has therapeutic potential as an antifungal drug, yet the
      mechanism of action remains ambiguous. Current study aimed to address the
      molecular process of the antifungal activity exerted by clove extract. METHODS
      AND RESULTS: The antifungal assay results showed that clove extract had some
      effects on all of the tested yeast. Propidium iodide staining assay showed cell
      membrane damage in Saccharomyces cerevisiae after treatment of clove extract for
      30 h. Interestingly, SDS-polyacrylamide gel electrophoresis assays revealed that
      the protein expression of eukaryotic elongation factor 1 alpha (eEF1A) was
      suppressed significantly after treatment with clove extract (not pure eugenol).
      Transcriptional analyses revealed that the TEF1 and TEF2 genes (translation
      elongation factor EF-1 alpha) encoding eEF1A were not disturbed with the addition
      of clove extract; however, the expression of related genes EFB1 (translation
      elongation factor 1 subunit beta), ENO2 (phosphopyruvate hydratase ENO2), GSP1
      (Ran GTPase GSP1), RPP0 (ribosomal protein P0), YEF3 (translation elongation
      factor EF-3), TEF4 (translation elongation factor EF1B gamma), and RPS2
      (ribosomal 40S subunit protein S2) increased significantly. CONCLUSIONS: These
      results suggest that clove extract plays a role in disrupting growth and
      affecting yeast metabolism. eEF1A was affected by clove extract at the protein
      level but not at the transcriptional level. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study is based on a detailed study of antifungal action exerted by clove
      extract, and proposed that down-regulation of eEF1A protein expression may
      contribute to its antifungal activity. These results may have clinical
      significance for future application of clove extract as a natural antifungal
      agent.

PMID- 28445617
TI  - A new society for the "New World".

PMID- 28445614
TI  - Two common human CLDN5 alleles encode different open reading frames but produce
      one protein isoform.
AB  - Claudins provide tight junction barrier selectivity. The human CLDN5 gene
      contains a high-frequency single-nucleotide polymorphism (rs885985), where the G
      allele codes for glutamine (Q) and the A allele codes for an amber stop codon.
      Thus, these different CLDN5 alleles define nested open reading frames (ORFs)
      encoding claudin-5 proteins that are 303 or 218 amino acids in length.
      Interestingly, human claudin-16 and claudin-23 also have long ORFs. The long form
      of claudin-5 contrasts with the majority of claudin-5 proteins in the National
      Center for Biotechnology Information protein database, which are less than 220
      amino acids in length. Screening of genotyped human lung tissue by immunoblot
      revealed only the 218 amino acid form of claudin-5 protein; the long-form claudin
      5 protein was not detected. Moreover, when forcibly expressed in transfected
      cells, the long form of human claudin-5 was retained in intracellular
      compartments and did not localize to the plasma membrane, in contrast to the 218
      amino acid form, which localized to intercellular junctions. This suggests that
      the 303 amino acid claudin-5 protein is rarely expressed, and, if so, is
      predicted to adversely affect cell function. Potential roles for upstream ORFs in
      regulating claudin-5 expression are also discussed.

PMID- 28445618
TI  - Ficolin-3/adiponectin ratio for the prediction of gestational diabetes mellitus
      in pregnant women.
AB  - AIMS/INTRODUCTION: To establish that the ficolin-3/adiponectin ratio is a
      predictor for gestational diabetes mellitus (GDM) and is eligible for screening
      tests for GDM. MATERIALS AND METHODS: A prospective cohort study of 86 pregnant
      women who developed GDM and 273 normal glucose tolerance participants was carried
      out. Maternal serum ficolin-3, adiponectin levels were investigated at 16-18
      weeks of gestation using enzyme-linked immunosorbent assay. RESULTS: Compared
      with the normal glucose tolerance group, the GDM group showed significantly
      higher levels of ficolin-3 and the ratio of ficolin-3/adiponectin; and decreased
      levels of adiponectin between 16-18 weeks of gestation (P < 0.05 or P < 0.01).
      The cut-off values for the ratio of ficolin-3/adiponectin (>=1.06; sensitivity
      90.9%, specificity 96.5%) to discriminate the pregnant women who developed GDM
      from the non-diabetic cases were identified using receiver operating
      characteristic analysis. Using binary logistic regression analysis, ficolin-3,
      retinol-binding protein-4 and adiponectin, but not C-reactive protein,
      triglyceride and free fatty acids were shown as predictive factors for GDM.
      CONCLUSIONS: The ratio of ficolin-3/adiponectin at 16-18 weeks of gestation was
      changed in pregnant women who subsequently developed GDM, and might provide
      effective early predicting and screening for GDM.

PMID- 28445619
TI  - mTOR inhibitors and risk of chronic antibody-mediated rejection after kidney
      transplantation: where are we now?
AB  - Antibody-mediated rejection (AMR) usually starts with generation of donor
      specific anti-HLA antibodies (DSAs), arising from a B-cell response to antigen
      recognition. In vitro and preclinical data demonstrate that mammalian target of
      rapamycin (mTOR) inhibition attenuates the mTOR-mediated intracellular signaling
      pathway involved in AMR-related kidney damage. The limited available data from
      immunological studies in kidney transplant patients, however, have not shown such
      effects in vivo. In terms of clinical immunosuppression, the overriding influence
      on rates of de novo DSA (dnDSA) or AMR-regardless of the type of regimen-is
      patient adherence. To date, limited data from patients given mTOR inhibitor
      therapy with adequate concurrent immunosuppression, such as reduced-exposure
      calcineurin inhibitor (CNI) therapy, have not shown an adverse effect on the risk
      of dnDSA or AMR. Early switch to an mTOR inhibitor (<6-12 months post-transplant)
      in a CNI-free regimen, in contrast, can increase the risk of dnDSA, especially if
      adjunctive therapy is inadequate. Late conversion to CNI-free therapy with mTOR
      inhibition does not appear to affect the risk of dnDSA. More data, from
      prospective studies, are required to fully understand that association between
      use of mTOR inhibitors with different types of concomitant therapy and risk of
      dnDSA and AMR.

PMID- 28445620
TI  - Smad4 Inhibits VEGF-A and VEGF-C Expressions via Enhancing Smad3 Phosphorylation
      in Colon Cancer.
AB  - Smad4 is a critical factor in the TGF-beta pathway and is involved in tumor
      progression and metastasis, but the role of Smad4 in colon cancer cells is
      unclear. The aim of this study is to explore the effect and the underlying
      mechanism of Smad4 on the growth, migration and apoptosis of colon cancer cells
      as well as vascular endothelial growth factor (VEGF)-A and VEGF-C secreted by
      these cells. In this study, we showed that Smad4, VEGF-A, and VEGF-C are
      independent prognostic factors of colon cancer, and Smad4 expression was
      negatively correlated with VEGF-A and -C in samples. We found that Smad4 mRNA and
      protein levels in colon cancer cells, particularly in HCT-116 cells, were
      significantly lower than those in the human intestinal epithelial cell line
      (HIEC). Smad4 overexpression promoted tumor cell apoptosis, inhibited VEGF-A and 
      C expression in vitro and in vivo, but had no effect on cell proliferation and
      migration. Tail vein injection of the virus inhibited xenograft growth in nude
      mice. Importantly, we also demonstrated that Smad4 could increase the
      phosphorylation level of Smad3, but not Smad2, which may be one of the mechanisms
      underlying these effects of Smad4 in colon cancer. Therefore, Smad4 may be a new
      target for the treatment of colon cancer. Anat Rec, 300:1560-1569, 2017. (c) 2017
      Wiley Periodicals, Inc.

PMID- 28445621
TI  - Calm to chaos: Engaging undergraduate nursing students with the complex nature of
      interruptions during medication administration.
AB  - AIMS AND OBJECTIVES: To describe undergraduate student nurse responses to a
      simulated role-play experience focussing on managing interruptions during
      medication administration. BACKGROUND: Improving patient safety requires that we
      find creative and innovative methods of teaching medication administration to
      undergraduate nurses in real-world conditions. Nurses are responsible for the
      majority of medication administrations in health care. Incidents and errors
      associated with medications are a significant patient safety issue and often
      occur as a result of interruptions. Undergraduate nursing students are generally
      taught medication administration skills in a calm and uninterrupted simulated
      environment. However, in the clinical environment medication administration is
      challenged by multiple interruptions. DESIGN/METHODS: A qualitative study using
      convenience sampling was used to examine student perceptions of a simulated role
      play experience. Data were collected from 451 of a possible 528 student written
      reflective responses and subject to thematic analysis. RESULTS: Students reported
      an increased understanding of the impacts of interruptions while administering
      medications and an improved awareness of how to manage disruptions. This study
      reports on one of three emergent themes: "Calm to chaos: engaging with the
      complex nature of clinical practice." CONCLUSIONS: Interrupting medication
      administration in realistic and safe settings facilitates awareness, allows for
      students to begin to develop management strategies in relation to interruption
      and increases their confidence. Students were given the opportunity to
      consolidate and integrate prior and new knowledge and skills through this role
      play simulation.

PMID- 28445622
TI  - Thiocarbohydrates on Gold Nanoparticles: Strong Influence of Stereocenters on
      Binding Affinity and Interparticle Forces.
AB  - Carbohydrates carrying thiol groups at the C-2 position have been attached to
      gold nanoparticles (AuNPs) with stereocenters in close proximity to the surface
      for the first time. Their configurations can be clearly distinguished by the
      tendency of particle aggregation. AuNP surface plasmon resonance (SPR), X-ray
      photoelectron spectroscopy (XPS), and IR spectroscopy indicate that the
      thiocarbohydrates replace citrate molecules at different rates, causing
      aggregation and eventually precipitation. A quantitative formulation of this
      aggregation process shows that reactivities can vary by several magnitudes.
      Adsorption isotherms and kinetics also demonstrate that the number of
      thiocarbohydrates varies by a factor of two. Molecular mechanics force field
      (MMFF) calculations reveal their relative orientations. Based on these models,
      the different binding behavior can be ascribed to attractive van der Waals forces
      and hydrogen bonds. Such interactions occur either between the carbohydrate and
      AuNPs, by lateral intermolecular forces at the surface, or by interparticle
      attraction, in analogy to cell-surface carbohydrates of biological recognition
      systems. Aggregation of NPs therefore act as an indicator to differentiate
      between various carbohydrates with defined configurations.

PMID- 28445623
TI  - Life-threatening injury caused by complete impalement of a toothbrush: Case
      report.
AB  - Toothbrushes are the most common cause of foreign body injury to the oral cavity
      in children, but complete impalement by a toothbrush is an extremely rare
      occurrence and has not been reported previously. This report describes a 28-month
      old girl who fell from a 1m ledge while brushing her teeth. Her toothbrush
      penetrated the oral cavity and could not be removed, and so she was rushed to the
      hospital with the toothbrush in place. Contrast-enhanced computed tomography
      showed penetration of the toothbrush from the oral cavity into and through the
      right posterior neck at the level of the bifurcation of the common carotid
      artery. Angiography was performed under general anesthesia, and the toothbrush
      was removed. In consultation with pediatricians, antibiotic infusion therapy was
      started, and the patient was extubated on the 5th post-operative day. There were
      no complications even after eating was resumed, and the patient was discharged on
      the 13th post-operative day. A toothbrush is an essential item in daily life, but
      it can cause serious injuries in children in some circumstances.

PMID- 28445624
TI  - The Role of Publicly Funded Family Planning Sites In Health Insurance Enrollment.
AB  - CONTEXT: Publicly funded family planning providers are well positioned to help
      uninsured individuals learn about health insurance coverage options and
      effectively navigate the enrollment process. Understanding how these providers
      are engaged in enrollment assistance and the challenges they face in providing
      assistance is important for maximizing their role in health insurance outreach
      and enrollment. METHODS: In 2014, some 684 sites participating in California's
      family planning program were surveyed about their involvement in helping clients
      enroll in health insurance. Weighted univariate and bivariate analyses were
      conducted to examine enrollment activities and perceived barriers to facilitating
      enrollment by site characteristics. RESULTS: Most family planning program sites
      provided eligibility screening (68%), enrollment education (77%), on-site
      enrollment assistance (55%) and referrals for off-site enrollment support (91%).
      The proportion of sites offering each type of assistance was highest among
      community clinics (83-96%), primary care and multispecialty sites (65-95%), Title
      X-funded sites (72-98%), sites with contracts to provide primary care services
      (64-93%) and sites using only electronic health records (66-94%). Commonly
      identified barriers to providing assistance were lack of staff time (reported by
      52% of sites), lack of funding (47%), lack of physical space (34%) and lack of
      staff knowledge (33%); only 20% of sites received funding to support enrollment
      activities. CONCLUSIONS: Although there were significant variations among them,
      publicly funded family planning providers in California are actively engaged in
      health insurance enrollment. Supporting their vital role in enrollment could help
      in the achievement of universal health insurance coverage.

PMID- 28445625
TI  - The use of an occlusion perfusion catheter to deliver paclitaxel to the arterial
      wall.
AB  - AIM: Nonstent drug delivery platforms have recently emerged as an alternative
      treatment of peripheral arterial disease. Perfusion catheters have the potential
      to directly deliver antiproliferative agents to the medial arterial layer to
      prevent restenosis. The purpose of this study was to therefore determine the
      effectiveness of a perfusion catheter to deliver paclitaxel, a proven
      antiproliferative agent, to combat restenosis. METHODS: A benchtop model was
      utilized to determine the varying parameters of a novel occlusion perfusion
      catheter to maximize paclitaxel delivery using pharmacokinetic evaluation and
      fluorescent microscopy. Parameters tested included concentration of paclitaxel,
      delivery pressure, duration of delivery, and the use of an excipient. In
      addition, bilateral rabbit iliac arteries were treated with the perfusion
      catheter and pharmacokinetic evaluation performed at 1 hour, 1 day and 3 days.
      RESULTS: Benchtop testing demonstrated uniform and circumferential penetration of
      paclitaxel within the treated arteries. The results of the ex vivo test
      identified two groups with and without an excipient with similar loading
      conditions (with excipient: 15.4+/-8.6 ng/mg vs without excipient: 8.9+/-6.9
      ng/mg, P=.77). The in vivo pharmacokinetic analysis of these two groups
      demonstrated the use of contrast agent increased arterial paclitaxel levels and
      maintained initial paclitaxel dosing up to 3 days (With excipient: 1 hour: 107+/
      62 ng vs 3 days: 40+/-23 ng, P=.824; No excipient: 1 hour: 247+/-120 ng vs 3
      days: 2.92+/-2.9 ng, P=.009). CONCLUSIONS: These results demonstrate the
      feasibility to deliver paclitaxel directly to the medial layer of an artery via a
      perfusion catheter.

PMID- 28445627
TI  - Psychosocial wellbeing after living kidney donation - a longitudinal, prospective
      study.
AB  - Living kidney donation (LKD) has become routine practice across the world as the
      gold standard treatment of end-stage renal failure. Whilst the physical risks and
      harms of LKD surgery are well documented, relatively little is known about
      psychosocial outcomes. The aim of this study was to determine whether it was
      possible to quantify the psychosocial impact of LKD. A prospective longitudinal
      study of 93 living kidney donors was performed. Data were collected
      preoperatively, and 3 and 12 months after donation. Questionnaires included 11
      validated psychosocial outcome measures and questions specific to LKD. Over time,
      there was no significant change in wellbeing, life satisfaction, self-esteem,
      social comparison, distress, depression, stress, anxiety or social support at 3
      or 12 months. Despite this, questions specific to LKD indicated that donors felt
      positively about donation, with low levels of regret. This study provides a
      thorough assessment of psychosocial outcomes after LKD over the first year.
      Donors felt positive about LKD although there was no evidence of any significant
      change in psychosocial outcomes. Despite no measurable psychosocial benefit after
      living kidney donation, there was also no evidence of harm.

PMID- 28445626
TI  - Fabrication and characterization of chitosan, polyvinylpyrrolidone, and cellulose
      nanowhiskers nanocomposite films for wound healing drug delivery application.
AB  - This study describes the preparation of composite film using chitosan (CS) and
      polyvinylpyrrolidone (PVP) with incorporated cellulose nanowhiskers (CNWs) for
      drug delivery application. CNWs were prepared by acid hydrolysis of cellulose
      with sulfuric acid. Field emission scanning electron microscopy studies revealed
      nanofibrous morphology of CNWs with 20-30 nm diameter and 200-250 nm in length. X
      ray powder diffraction analysis confirmed highly crystalline nature of CNWs with
      92.81% crystallinity. Incorporation of CNWs enhanced the thermal and mechanical
      properties of films. Fourier transform infrared spectroscopy data showed physical
      interactions between polymer-polymer and polymer-drug. Films prepared with CNWs
      showed improved swelling behavior which resulted in sustained drug release from
      polymeric matrix. In vitro curcumin release data were fitted with two-step
      release model; Step 1 as desorption from the outer surface of the film, and Step
      2 as diffusion from within the film and subsequent desorption. The release
      kinetics confirmed biphasic release profile with different release rates along
      with diffusion controlled curcumin release. Prepared films showed high
      biocompatibility with excellent antibacterial activities. Overall, the performed
      studies confirmed CS-PVP-CNWs based release system can as a potential candidate
      for wound dressing applications with sustained drug release. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2391-2404, 2017.

PMID- 28445629
TI  - N-Acetonitrile Functionalized Nitropyrazoles: Precursors to Insensitive
      Asymmetric N-Methylene-C Linked Azoles.
AB  - Properties of energetic compounds obtained by linking energetic pyrazoles to
      tetrazoles by means of N-methylene-C bridges can be fine-tuned. Reactions of
      pyrazole derivatives with chloroacetonitrile followed by conversion of the cyano
      group to tetrazole using click reactions in the presence of zinc chloride result
      in asymmetric N-methylene-C bridged azole-based energetic compounds. All the
      compounds were thoroughly characterized by IR and NMR [1 H, 13 C {1 H}, 15 N]
      spectroscopy, elemental analysis, and differential scanning calorimetry (DSC),
      and for two compounds, further supported by single-crystal X-ray diffraction
      studies. Heats of formation and detonation performances were calculated using
      Gaussian 03 and EXPLO5 v6.01 programs, respectively. Initial studies show that
      this new approach is promising for synthesizing less sensitive energetic
      compounds with fine-tuned properties.

PMID- 28445630
TI  - Murai Reaction on Furfural Derivatives Enabled by Removable N,N'-Bidentate
      Directing Groups.
AB  - Furfural and related compounds are industrially relevant building blocks obtained
      from lignocellulosic biomass. To enhance the added value of these renewable
      resources, a Ru-catalyzed hydrofurylation of alkenes, involving a directed C-H
      activation at C3 of the furan ring, was developed. A thorough experimental study
      revealed that a bidentate amino-imine directing group enabled the desired
      coupling. Removal of the directing group occurred during the purification step,
      directly releasing the C3-functionalized furfurals. Development of the reaction
      as well as optimization and scope of the method were described. A mechanism was
      proposed on the basis of DFT calculations.

PMID- 28445628
TI  - Characterization of four Latin American families confirms previous findings and
      reveals novel features of acid-labile subunit deficiency.
AB  - OBJECTIVE: Acid-labile subunit deficiency (ACLSD), caused by inactivating
      mutations in both IGFALS gene alleles, is characterized by marked reduction in
      IGF-I and IGFBP-3 levels associated with mild growth retardation. The aim of this
      study was to expand the known phenotype and genetic characteristics of ACLSD by
      reporting data from four index cases and their families. DESIGN: Auxological
      data, biochemical and genetic studies were performed in four children diagnosed
      with ACLSD and all available relatives. METHODS: Serum levels of IGF-I, IGFBP-3,
      acid-labile subunit (ALS), and in vitro ternary complex formation (ivTCF) were
      determined. After sequencing the IGFALS gene, pathogenicity of novel identified
      variants was evaluated by in vitro expression in transfected Chinese hamster
      ovarian (CHO) cells. ALS protein was detected in patients' sera and CHO cells
      conditioned media and lysates by Western immunoblot (WIB). RESULTS: Four index
      cases and four relatives were diagnosed with ACLSD. The following variants were
      found: p.Glu35Glyfs*17, p.Glu35Lysfs*87, p.Leu213Phe, p.Asn276Ser, p.Leu409Phe,
      p.Ala475Val and p.Ser490Trp. ACLSD patients presented low IGF-I and low or
      undetectable levels of IGFBP-3 and ALS. Seven out of 8 patients did not form
      ivTCF. CONCLUSIONS: This study confirms previous findings in ACLSD, such as the
      low IGF-I and a more severe reduction in IGFBP-3 levels, and a gene dosage effect
      observed in heterozygous carriers (HC). In addition, father-to-son transmission
      (father compound heterozygous and mother HC), preservation of male fertility, and
      marginal ALS expression with potential involvement in preserved responsiveness to
      rhGH treatment, are all novel aspects, not previously reported in this condition.

PMID- 28445631
TI  - Treating Prolonged Grief Disorder: A 2-Year Follow-Up of a Randomized Controlled
      Trial.
AB  - BACKGROUND: Prolonged grief disorder (PGD) causes significant impairment in
      approximately 7% of bereaved people. Although cognitive-behavioral therapy (CBT)
      has been shown to effectively treat PGD, there is no evidence of long-term
      effects of CBT. OBJECTIVE: To determine the long-term efficacies of CBT with
      exposure or CBT without exposure in treating PGD by assessing outcome at 2 years.
      METHODS: A randomized controlled trial of PGD patients (N = 80) attending an
      outpatient clinic took place between September 2007 and June 2010, and a 2-year
      follow-up occurred between December 2009 and October 2012. All patients received
      10 weekly 2-hour group therapy sessions that comprised CBT techniques. Patients
      also received 4 individual sessions in which they were randomly allocated to
      receive exposure therapy (CBT/Exposure) for memories of the death or supportive
      counseling (CBT). Prolonged grief disorder was assessed by clinical interview
      using the Complicated Grief Assessment. Severity of PGD, the primary outcome, was
      assessed using the Inventory of Complicated Grief. RESULTS: Intent-to-treat
      analyses indicated a significant linear time * treatment condition interaction
      effect at 2 years (B = -0.63; SE = 0.26; t225 = -2.44; P = .02; 95% CI, -1.14 to 
      0.12), indicating that CBT/Exposure led to greater reductions in PGD than CBT.
      Further, the linear between-group effect size at the 2-year follow-up was 1.15.
      CONCLUSIONS: Exposure therapy in the course of CBT leads to greater reduction in
      symptoms of PGD than CBT without exposure, and this additive gain extends 2 years
      after treatment is complete. To achieve optimal treatment gains in patients with
      PGD, therapists should encourage some form of exposure therapy to memories of the
      death. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      identifier: ACTRN12609000229279.

PMID- 28445633
TI  - Advanced Glycation End Products in Recent-Onset Psychosis Indicate Early Onset of
      Cardiovascular Risk.
AB  - OBJECTIVE: Profoundly increased mortality rates in schizophrenia, largely caused
      by a higher risk and earlier onset of cardiovascular disease, remain a major
      challenge. During the human lifespan, advanced glycation end products (AGEs)
      accumulate, and their concentration is strongly linked to cardiovascular
      mortality. AGE accumulation can be accelerated by several pathways, including
      oxidative stress. METHODS: From March 2015 through January 2016, a case-control
      study including 111 patients with a recent-onset psychosis, 135 controls from a
      validation cohort, and 286 healthy controls was performed. Patients fulfilled the
      DSM-IV criteria for schizophrenia spectrum disorders with an illness duration
      shorter than 5 years. Main outcome parameters were skin autofluorescence levels
      of AGEs, controlled for age, gender, and smoking. Correlations of AGEs with
      cardiovascular risk factors and clinical variables were analyzed by hierarchical
      linear regression analyses. RESULTS: An AGE measurement was possible in 77.4% of
      cases. AGEs were elevated by 15.1% in recent-onset psychosis compared to healthy
      controls (P < .001), corresponding to an increased accumulation of AGEs normally
      occurring in approximately 10 years. AGEs were not related to traditional risk
      factors. However, duration of illness (P = .008), duration of antipsychotic
      treatment (P = .009), and cumulative exposure to antipsychotics (P = .023)
      correlated with AGEs. CONCLUSIONS: Patients with a recent onset of psychosis have
      increased AGE levels compared to healthy controls. These findings argue for an
      earlier implementation of treatment strategies aimed at preventing cardiovascular
      disease. Also, low-dose strategies of antipsychotics in schizophrenia could
      beneficially influence AGE levels.

PMID- 28445632
TI  - The Association of Baseline Suicidality With Treatment Outcome in Psychotic
      Depression.
AB  - OBJECTIVE: To examine the association between baseline suicidality and outcome of
      major depression in a randomized controlled trial of the pharmacotherapy of
      psychotic depression and to explore the interaction of suicidality, randomized
      treatment assignment, and depression outcome. METHODS: This study was a secondary
      analysis of data from 258 persons aged 18 years or older with DSM-IV-defined
      major depressive disorder with psychotic features who participated in a 12-week
      randomized controlled trial (RCT) comparing olanzapine plus sertraline with
      olanzapine plus placebo (the Study of the Pharmacotherapy of Psychotic Depression
      [STOP-PD], which ran from 2002 to 2007). The independent variable was baseline
      suicidality, defined by 4 groups (suicide attempt in the current episode, active
      suicidal ideation, passive suicidal ideation, and no suicidality). The outcome
      variables were change in 16-item Hamilton Depression Rating Scale (HDRS16) total
      score (excluding the suicide item) over time and remission of psychotic
      depression over time. RESULTS: Suicidality groups did not significantly differ on
      baseline HDRS16 total score. Baseline suicidality group was significantly
      associated with change in HDRS16 score over time in the sample as a whole
      (F3,1394 = 8.17; P < .0001), but was not significantly associated with
      probability of remission over time. Among participants assigned to olanzapine and
      placebo, persons with no suicidality had a significantly greater reduction in
      HDRS16 total score compared to those with passive suicidal ideation (7.5-point
      difference in change scores between the 2 groups; 95% CI, 4.3-10.7 t1394 = 4.61,
      P < .0001), active suicidal ideation (4.4 points; 95% CI, 1.4-7.4; t1394 = 2.85,
      P = .0176), or suicide attempts (6.1 points; 95% CI, 2.8-9.4; t1394 = 3.66, P =
      .0015). The 12-week change from baseline in HDRS16 score for patients with no
      suicidality was not significantly different between the 2 treatment arms.
      However, the 12-week HDRS16 improvement was significantly greater in the
      olanzapine plus sertraline arm, compared with the olanzapine plus placebo arm,
      for patients with suicide attempts (8.7-point difference in change scores between
      the 2 groups; 95% CI, 5.1-12.4; t1394 = 4.75, P < .0001), active suicidal
      ideation (8.1 points; 95% CI, 4.5-11.7; t1394 = 4.38, P < .0001), or passive
      suicidal ideation (5.7 points; 95% CI, 2.2-9.2; t1394 = 3.23, P = .0012),
      respectively. CONCLUSIONS: Baseline suicidality predicted worse acute treatment
      outcome of psychotic depression. However, participants with suicidality had a
      better outcome when treated with the combination of olanzapine and sertraline
      than when treated with olanzapine plus placebo. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00056472.

PMID- 28445634
TI  - Low-Temperature Associated Interface Influence on the Black Phosphorus
      Nanoflakes.
AB  - The temperature-dependent structure properties of few-layer black phosphorus (BP)
      nanoflakes supported on the Si substrate and suspended on the holes are
      investigated using the Raman spectroscopy in the range of 77-293 K. The
      temperature coefficients of three main Raman modes for supported BP are larger
      than those of suspended BP because of the interface effects, mainly the tensile
      strain and the different thermal expansion coefficients (TEC) between the
      substrate and BP nanoflakes. The out-of-plane vibration is more apt to be
      affected by the initial strain, whereas the influence on the in-plane vibrations
      is negligible. During the varied temperature circulation, the temperature
      coefficients in the heating process are much larger than those in the cooling
      process because of the interface influences. Thus, the interfacial interaction
      between BP and the substrate plays an important role in the thermal-mechanical
      properties of BP. These findings pave a way for the further study of thermal
      mechanical related applications of flexible BP nanodevices.

PMID- 28445635
TI  - Synthesis and Enhanced Corrosion Protection Performance of Reduced Graphene Oxide
      Nanosheet/ZnAl Layered Double Hydroxide Composite Films by Hydrothermal
      Continuous Flow Method.
AB  - Prevention of water, oxygen, and chloride ions contained in hydrotalcite
      interlayers from diffusing through the layered double hydroxides (LDH) is of
      crucial importance in corrosion protection. In this work, a hybrid composed of
      reduced graphene oxide (RGO) nanosheets/Zn2+/Al3+ layered double hydroxide
      (RGO/ZnAl-LDH) composite films on the surface of 6N01 aluminum (Al) alloy was
      successfully synthesized by a novel and facile hydrothermal continuous flow
      method, which enabled direct growth of the composite on the surface of the Al
      alloy substrate. The structure and morphology of the RGO/ZnAl-LDH composite films
      were fully characterized. Based on electrochemical measurements in a NaCl
      solution, the RGO/ZnAl-LDH composite film significantly enhanced the corrosion
      protection, as compared with the ZnAl-LDH film. The RGO/ZnAl-LDH composite film
      could maintain an outstanding corrosion resistance after 7 days immersion in a
      high concentration of NaCl solution (i.e., 5.0 wt %). The enhanced corrosion
      resistance was attributed to the barrier effect on diffusion of water, oxygen,
      and chloride ions by the RGO contained in the RGO/ZnAl-LDH composite films.

PMID- 28445636
TI  - Disposable Autonomous Device for Swab-to-Result Diagnosis of Influenza.
AB  - A prototype of a self-contained, automated, disposable device for chemically
      amplified protein-based detection of influenza virus from nasal swab specimens
      was developed and evaluated in a clinical setting. The device required only
      simple specimen manipulation without any dedicated instrumentation or specialized
      training by the operator for interpretation. The device was based on a sandwich
      immunoassay for influenza virus nucleoprotein; it used an enzyme-labeled antibody
      and a chromogenic substrate to provide an amplified visible signal, in a two
      dimensional paper network format. All reagents were stored within the device.
      Device performance was assessed at Seattle Children's Hospital; clinical staff
      collected nasal swab samples from 25 patients and then operated test devices on
      site to detect influenza A and B in those specimens. The total test time from
      device initiation to result was approximately 35 min. Device performance for
      influenza A detection was ~70% accurate using in-house qRT-PCR influenza A as a
      gold-standard comparison. The ratio of valid to total completed device runs
      yielded a success rate of 92%, and the negative predictive value for both the
      influenza A and B assay was 81%. The ability to diagnose respiratory infections
      rapidly and close to the patient was well received by hospital staff, inspiring
      further optimization of device function.

PMID- 28445637
TI  - Control of Charge Carriers Trapping and Relaxation in Hematite by Oxygen Vacancy
      Charge: Ab Initio Non-adiabatic Molecular Dynamics.
AB  - Ultrafast charge recombination in hematite (alpha-Fe2O3) severely limits its
      applications in solar energy conversion and utilization, for instance, in
      photoelectrochemical water splitting. We report the first time-domain ab initio
      study of charge relaxation dynamics in alpha-Fe2O3 with and without the oxygen
      vacancy (Ov) defect, using non-adiabatic molecular dynamics implemented within
      time-dependent density functional theory. The simulations show that the hole
      trapping is the rate-limiting step in the electron-hole recombination process for
      both neutral and ionized Ov systems. The electron trapping is fast, and the
      trapped electron are relatively long-lived. A similar asymmetry is found for the
      relaxation of free charge carriers: relaxation of photoholes in the valence band
      is slower than relaxation of photoelectrons in the conduction band. The slower
      dynamics of holes offers an advantage to water oxidation at alpha-Fe2O3
      photoanodes. Notably, the neutral Ov defect accelerates significantly the charge
      recombination rate, by about a factor of 30 compared to the ideal lattice, due to
      the stronger electron-vibrational coupling at the defect. However, the
      recombination rate in the ionized Ov defect is decreased by a factor of 10 with
      respect to the neutral defect, likely due to expansion of the local iron shell
      around the Ov site. The Ov defect ionization in alpha-Fe2O3 photoanodes is
      important for increasing both electrical conductivity and charge carrier
      lifetimes. The simulations reproduce well the time scales for the hot carrier
      cooling, trapping and recombination available from transient spectroscopy
      experiments, and suggest two alternative mechanisms for the Ov-assisted electron
      hole recombination. The study provides a detailed atomistic understanding of
      carrier dynamics in hematite, and rationalizes the experimentally reported
      activation of alpha-Fe2O3 photoanodes by incorporation of Ov defects.

PMID- 28445638
TI  - Antigenic GM3 Lactone Mimetic Molecule Integrated Mannosylated Glycopeptide
      Nanofibers for the Activation and Maturation of Dendritic Cells.
AB  - The ability of dendritic cells to coordinate innate and adaptive immune responses
      makes them essential targets for vaccination strategies. Presentation of specific
      antigens by dendritic cells is required for the activation of the immune system
      against many pathogens and tumors, and nanoscale materials can be functionalized
      for active targeting of dendritic cells. In this work, we integrated an
      immunogenic, carbohydrate melanoma-associated antigen-mimetic GM3-lactone
      molecule into mannosylated peptide amphiphile nanofibers to target dendritic
      cells through DC-SIGN receptor. Based on morphological and functional analyses,
      when dendritic cells were treated with peptide nanofiber carriers, they showed
      significant increase in antigen internalization and a corresponding increase in
      the surface expression of the activation and maturation markers CD86, CD83 and
      HLA-DR, in addition to exhibiting a general morphology consistent with dendritic
      cell maturation. These results indicate that mannosylated peptide amphiphile
      nanofiber carriers are promising candidates to target dendritic cells for antigen
      delivery.

PMID- 28445640
TI  - Highly Active and Stable Fe-N-C Catalyst for Oxygen Depolarized Cathode
      Applications.
AB  - Anion immunity toward the oxygen reduction reaction (ORR) has tremendous
      implications in electrocatalysis with applications for fuel cells, metal-air
      batteries, and oxygen depolarized cathodes (ODCs) in the anodic evolution of
      chlorine. The necessity of exploring ORR catalysts with immunity to anion
      adsorption is particularly significant considering that platinum group metal
      (PGM) catalysts are costly and highly vulnerable to impurities such as halides.
      Herein, we report a metal organic framework (MOF)-derived Fe-N-C catalyst that
      exhibits a dramatically improved half-wave potential of 240 mV compared to the
      state-of-the-art RhxSy/C catalyst in a rotating disk electrode in the presence of
      Cl-. The Fe-N4 active sites in Fe-N-C are intrinsically immune to Cl- poisoning,
      in contrast to Pt/C, which is severely susceptible to Cl- poisoning. As a result,
      the activity of Fe-N-C decreases only marginally in the presence of Cl-, far
      exceeding that of Pt/C. The viability of this catalyst as ODCs is further
      demonstrated in real-life hydrochloric acid electrolyzers using highly
      concentrated HCl solution saturated with Cl2 gas as the electrolyte. The
      introduction of Fe-N-C materials as ODC catalysts here overcomes the limitations
      of (i) the low intrinsic ORR activity of RhxSy/C as the state-of-the-art ODC
      catalyst; (ii) the vulnerability to Cl- poisoning of Pt/C as the state-of-the-art
      ORR catalyst; and (iii) the high cost of precious metals in these two materials,
      resulting in a cost-effective ODC catalyst with the overall performance exceeding
      that of all previously reported materials.

PMID- 28445639
TI  - Toward Covalent Organic Frameworks Bearing Three Different Kinds of Pores: The
      Strategy for Construction and COF-to-COF Transformation via Heterogeneous Linker
      Exchange.
AB  - Covalent organic frameworks (COFs) are an emerging class of crystalline porous
      organic materials which are fabricated via reticular chemistry. Their topologic
      structures can be precisely predicted on the basis of the structures of building
      blocks. However, constructing COFs with complicated structures has remained a
      great challenge, due to the limited strategies that can access to the structural
      complexity of COFs. In this work, we have developed a new approach to produce
      COFs bearing three different kinds of pores. The design is fulfilled by the
      combination of vertex-truncation with multiple-linking-site strategy. On the
      basis of this design, a "V"-shaped building block carrying two aldehyde groups on
      the end of each branch has been synthesized. Condensation of it with 1,4
      diaminobenzene or benzidine leads to the formation of two triple-pore COFs, TP
      COF-DAB and TP-COF-BZ, respectively. The topological structures of the triple
      pore COFs have been confirmed by PXRD studies, synchrotron small-angle X-ray
      scattering (SAXS) experiments, theoretical simulations, and pore size
      distribution analyses. Furthermore, for the first time, an in situ COF-to-COF
      transformation has also been achieved by heating TP-COF-BZ with 1,4
      diaminobenzene under solvothermal condition, which leads to the formation of TP
      COF-DAB via in situ replacing the benzidine linkers in TP-COF-BZ with 1,4
      diaminobenzene linkers.

PMID- 28445641
TI  - Exfoliation of LiNi1/3Mn1/3Co1/3O2 into Nanosheets Using Electrochemical
      Oxidation and Reassembly with Dialysis or Flocculation.
AB  - Two-dimensional (2D) materials such as nanosheets are increasingly attracting
      attention for applications in energy storage and conversion. Many conventional
      battery compounds have layered structures, which can facilitate the exfoliation
      of these materials into nanosheet morphologies. In this work, LiNi1/3Mn1/3Co1/3O2
      (NMC) particles were exfoliated into nanosheets using an electrochemical
      oxidation method enabled by the intercalation of tetraethylammonium cations into
      the interlayer space. The exfoliated materials were monolayer or double-layer
      nanosheets with hexagonal shapes and sizes of <50 nm. Two different methods were
      used to reassemble the nanosheets into NMC particles: (1) a slow, dialysis-based
      approach and (2) direct flocculation. Characterization of the NMC materials at
      different stages in the exfoliation and reassembly processes was performed using
      compositional analysis, X-ray diffraction, electron microscopy, and
      electrochemical methods. The dialysis reassembly method allowed for the
      restacking of the nanosheets into faceted, hexagonally shaped nanoplatelets, and
      the flocculation approach yielded only ill-defined particles. The differences in
      the observed potential-dependent redox behavior and electrochemical cycling
      characteristics are attributed to the role of the reassembly method in the
      formation of phase-segregated domains, with the particles reassembled using the
      dialysis approach displaying the best performance.

PMID- 28445642
TI  - Predictive Power of Clean Bed Filtration Theory for Fecal Indicator Bacteria
      Removal in Stormwater Biofilters.
AB  - Green infrastructure (also referred to as low impact development, or LID) has the
      potential to transform urban stormwater runoff from an environmental threat to a
      valuable water resource. In this paper we focus on the removal of fecal indicator
      bacteria (FIB, a pollutant responsible for runoff-associated inland and coastal
      beach closures) in stormwater biofilters (a common type of green infrastructure).
      Drawing on a combination of previously published and new laboratory studies of
      FIB removal in biofilters, we find that 66% of the variance in FIB removal rates
      can be explained by clean bed filtration theory (CBFT, 31%), antecedent dry
      period (14%), study effect (8%), biofilter age (7%), and the presence or absence
      of shrubs (6%). Our analysis suggests that, with the exception of shrubs, plants
      affect FIB removal indirectly by changing the infiltration rate, not directly by
      changing the FIB removal mechanisms or altering filtration rates in ways not
      already accounted for by CBFT. The analysis presented here represents a
      significant step forward in our understanding of how physicochemical theories
      (such as CBFT) can be melded with hydrology, engineering design, and ecology to
      improve the water quality benefits of green infrastructure.

PMID- 28445643
TI  - Pinhole-Free Hybrid Perovskite Film with Arbitrarily-Shaped Micro-Patterns for
      Functional Optoelectronic Devices.
AB  - In many optoelectronic applications, patterning is required for functional and/or
      aesthetic purposes. However, established photolithographic technique cannot be
      applied directly to the hybrid perovskites, which are considered as promising
      candidates for optoelectronic applications. In this work, a wettability-assisted
      photolithography (WAP) process, which employs photolithography and one-step
      solution process to deposit hybrid perovskite, was developed for fabricating
      patterned hybrid perovskite films. Uniform pinhole-free hybrid perovskite films
      with sharp-edged micropatterns of any shapes can be constructed through the WAP
      process. Semitransparent solar cells with an adjustable active layer average
      visible transmittance of a wide range from 20.0% to 100% and regular solar cells
      based on patterned CH3NH3PbI3 perovskite films were fabricated to demonstrate
      that the WAP process was compatible with the manufacturing process of
      optoelectronic devices. With the widely equipped photolithographic facilities in
      the modern semiconductor industry, we believe the WAP process have a great
      potential in the industrial production of functionally or aesthetically patterned
      hybrid perovskite devices.

PMID- 28445644
TI  - Broadband Fluorescence Enhancement with Self-Assembled Silver Nanoparticle
      Optical Antennas.
AB  - Plasmonic structures are known to affect the fluorescence properties of dyes
      placed in close proximity. This effect has been exploited in combination with
      single-molecule techniques for several applications in the field of biosensing.
      Among these plasmonic structures, top-down zero-mode waveguides stand out due to
      their broadband capabilities. In contrast, optical antennas based on gold
      nanostructures exhibit fluorescence enhancement on a narrow fraction of the
      visible spectrum typically restricted to the red to near-infrared region. In this
      contribution, we exploit the DNA origami technique to self-assemble optical
      antennas based on large (80 nm) silver nanoparticles. We have studied the
      performance of these antennas with far- and near-field simulations and
      characterized them experimentally with single-molecule fluorescence measurements.
      We demonstrate that silver-based optical antennas can yield a fluorescence
      enhancement of more than 2 orders of magnitude throughout the visible spectral
      range for high intrinsic quantum yield dyes. Additionally, a comparison between
      the performance of gold and silver-based antennas is included. The results
      indicate that silver-based antennas strongly outperform their gold counterparts
      in the blue and green ranges and exhibit marginal differences in the red range.
      These characteristics render silver-based optical antennas ready for applications
      involving several fluorescently labeled species across the visible spectrum.

PMID- 28445645
TI  - Simultaneous Ni Doping at Atom Scale in Ceria and Assembling into Well-Defined
      Lotuslike Structure for Enhanced Catalytic Performance.
AB  - Oxide materials with redox capability have attracted worldwide attentions in many
      applications. Introducing defects into crystal lattice is an effective method to
      modify and optimize redox capability of oxides as well as their catalytic
      performance. However, the relationship between intrinsic characteristics of
      defects and properties of oxides has been rarely reported. Herein, we report a
      facile strategy to introduce defects by doping a small amount of Ni atoms (~1.8
      at. %) into ceria lattice at atomic level through the effect of microstructure of
      crystal on the redox property of ceria. Amazingly, a small amount of single Ni
      atom-doped ceria has formed a homogeneous solid solution with uniform lotuslike
      morphology. It performs an outstanding catalytic performance of a reduced T50 of
      CO oxidation at 230  degrees C, which is 135  degrees C lower than that of pure
      CeO2 (365  degrees C). This is largely attributed to defects such as lattice
      distortion, crystal defects and elastic strain induced by Ni dopants. The DFT
      calculation has revealed that the electron density distribution of oxygen ions
      near Ni dopant, the reduced formation energy of oxygen vacancy originated from
      local chemical effect caused by local distortion after Ni doping. These
      differences have a great effect on increasing the concentration of oxygen
      vacancies and enhancing the migration of lattice oxygen from bulk to a surface
      which is closely related to optimized redox properties. As a result, oxygen
      storage capacity and the associated catalytic reactivity has been largely
      increased. We have clearly demonstrated the change of crystal lattice and the
      charge distribution effectively modify its chemical and physical properties at
      the atomic scale.

PMID- 28445646
TI  - Spinning Hierarchical Gold Nanowire Microfibers by Shear Alignment and
      Intermolecular Self-Assembly.
AB  - Hierarchical structures lend strength to natural fibers made of soft nanoscale
      building blocks. Intermolecular interactions connect the components at different
      levels of hierarchy, distribute stresses, and guarantee structural integrity
      under load. Here, we show that synthetic ultrathin gold nanowires with
      interacting ligand shells can be spun into biomimetic, free-standing microfibers.
      A solution spinning process first aligns the wires, then lets their ligand shells
      interact, and finally converts them into a hierarchical superstructure. The
      resulting fiber contained 80 vol % organic ligand but was strong enough to be
      removed from the solution, dried, and mechanically tested. Fiber strength
      depended on the wire monomer alignment. Shear in the extrusion nozzle was
      systematically changed to obtain process-structure-property relations. The degree
      of nanowire alignment changed breaking stresses by a factor of 1.25 and the
      elongation at break by a factor of 2.75. Plasma annealing of the fiber to form a
      solid metal shell decreased the breaking stress by 65%.

PMID- 28445647
TI  - How Will Copper Contamination Constrain Future Global Steel Recycling?
AB  - Copper in steel causes metallurgical problems, but is pervasive in end-of-life
      scrap and cannot currently be removed commercially once in the melt.
      Contamination can be managed to an extent by globally trading scrap for use in
      tolerant applications and dilution with primary iron sources. However, the
      viability of long-term strategies can only be evaluated with a complete
      characterization of copper in the global steel system and this is presented in
      this paper. The copper concentration of flows along the 2008 steel supply chain
      is estimated from a survey of literature data and compared with estimates of the
      maximum concentration that can be tolerated in steel products. Estimates of final
      steel demand and scrap supply by sector are taken from a global stock-saturation
      model to determine when the amount of copper in the steel cycle will exceed that
      which can be tolerated. Best estimates show that quantities of copper arising
      from conventional scrap preparation can be managed in the global steel system
      until 2050 assuming perfectly coordinated trade and extensive dilution, but this
      strategy will become increasingly impractical. Technical and policy interventions
      along the supply chain are presented to close product loops before this global
      constraint.

PMID- 28445648
TI  - Electron Radiolysis of Ammonium Perchlorate: A Reflectron Time-of-Flight Mass
      Spectrometric Study.
AB  - Thin films of ammonium perchlorate (NH4ClO4) were exposed to energetic electrons
      at 5.5 K to explore the radiolytic decomposition mechanisms. The effects of
      radiolysis were monitored on line and in situ via Fourier transform infrared
      spectroscopy (FTIR) in the condensed phase along with electron impact ionization
      quadrupole mass spectrometry (EI-QMS) and single-photon photoionization
      reflectron time-of-flight mass spectrometry (PI-ReTOF-MS) during the temperature
      programmed desorption (TPD) phase to probe the subliming molecules. Three classes
      of molecules were observed: (i) nitrogen bearing species [ammonia (NH3),
      hydroxylamine (NH2OH), molecular nitrogen (N2), nitrogen dioxide (NO2)], (ii)
      chlorine carrying molecules [chlorine monoxide (ClO), chlorine dioxide (ClO2),
      dichlorine trioxide (Cl2O3)], and (iii) molecular oxygen (O2). Decay profiles of
      the reactants along with the growth profiles of the products as derived from the
      infrared data were fit kinetically to obtain a reaction mechanism with the
      initial steps involving a proton loss from the ammonium ion (NH4+) yielding
      ammonia (NH3) and the decomposition of perchlorate ion (ClO4-) forming chlorate
      ion (ClO3-) plus atomic oxygen. The latter oxidized ammonia to hydroxylamine and
      ultimately to nitrogen dioxide. Molecular oxygen and nitrogen were found to be
      formed via recombination of atomic oxygen and multistep radiolysis of ammonia,
      respectively.

PMID- 28445651
TI  - Herbicide targets and detoxification proteins in sugarcane: from gene assembly to
      structure modelling.
AB  - In a genome context, sugarcane is a classic orphan crop, in that no genome and
      only very few genes have been assembled. We have devised a novel exome assembly
      methodology that has allowed us to assemble and characterize 49 genes that serve
      as herbicide targets, safener interacting proteins, and members of herbicide
      detoxification pathways within the sugarcane genome. We have structurally
      modelled the products of each of these genes, as well as determining allelic,
      genomic, and RNA-Seq based polymorphisms for each gene. This study provides the
      largest collection of sugarcane structures modelled to date. We demonstrate that
      sugarcane genes are highly polymorphic, revealing that each genotype is evolving
      both uniquely and independently. In addition, we present an exome assembly system
      for orphan crops that can be executed on commodity infrastructure, making exome
      assembly practical for any group. In terms of knowledge about herbicide modes of
      action and detoxification, we have advanced sugarcane from a crop where no
      information about any herbicide-associated gene was available to the situation
      where sugarcane is now a species with the single largest collection of known and
      annotated herbicide-associated genes.

PMID- 28445649
TI  - High Serum Stability of Collagen Hybridizing Peptides and Their Fluorophore
      Conjugates.
AB  - Collagen hybridizing peptides (CHPs) have a great potential for use in targeted
      drug delivery, diagnostics, and regenerative medicine due to their ability to
      specifically bind to denatured collagens associated with many pathologic
      conditions. Since peptides generally suffer from poor enzymatic stability,
      resulting in rapid degradation and elimination in vivo, CHP's serum stability is
      a critical parameter that may dictate its pharmacokinetic behavior. Here, we
      report the serum stability of a series of monomeric CHP derivatives and establish
      how peptide length, amino acid composition, terminal modification, and linker
      chemistry influence their availability in serum. We show that monomeric CHPs
      comprised of the collagen-like Gly-Pro-Hyp motif are resistant to common serum
      proteinases and that their stability can be further increased by simple N
      terminal labeling which negates CHP's susceptibility to proline-specific
      exopeptidases. When fluorescent dyes are conjugated to a CHP via maleimide-thiol
      reaction, the dye can transfer from CHP onto serum proteins (e.g., albumin),
      resulting in an unexpected drop in signal during serum stability assays and off
      target accumulation during in vivo tests. This work is the crucial first step
      toward understanding the pharmacokinetic behavior of CHPs, which can facilitate
      the development of CHP-based theranostics.

PMID- 28445650
TI  - CXCR4-Targeted and Redox Responsive Dextrin Nanogel for Metastatic Breast Cancer
      Therapy.
AB  - The unsatisfied results of cancer therapy are caused by many issues and
      metastasis of cancer cells is one of the major challenge. It has been reported
      that inhibiting the SDF1/CXCR4 interaction can significantly reduce the
      metastasis of breast cancer cells to regional lymph nodes and lung. Herein, a
      nanogel system equipped with the FDA-approved CXCR4 antagonist AMD3100 was
      developed and evaluated for its combined antimetastatic and tumor targeting
      effects. Briefly, a bioreducible cross-linked dextrin nanogel (DNG) coated with
      AMD3100 was designed to possess multiple functions, including CXCR4 chemokine
      targeting, inhibition of tumor metastasis, and reduction-responsive intracellular
      release of doxorubicin (DOX) to reduce the cells proliferation. The in vitro
      results confirmed that the DOX-loaded AMD3100-coated dextrin nanogel (DOX-AMD
      DNG) was more effectively taken up by 4T1 breast cancer cells than DOX-DNG and
      was significantly more cytotoxic to 4T1 cells than DOX-DNG. In biodistribution
      studies, the stronger fluorescence intensity of Cy7-AMD-DNG than Cy7-DNG further
      confirmed that AMD3100 mediated tumor targeting in vivo. AMD3100-coated DOX-DNG
      also exhibited a distinct antimetastatic effect and CXCR4 antagonistic activity
      by inhibiting CXCR4-mediated cell invasion in 4T1 and U2OS cells. Moreover, DOX
      AMD-DNG displayed superior anticancer activity and antimetastatic effects in
      orthotopic breast cancer-bearing Balb/C mice. In summary, the multifunctional DOX
      AMD-DNG can effectively target the tumor site and dually impede cancer
      progression and metastasis.

PMID- 28445652
TI  - Identification of quantitative trait loci underlying seed protein content of
      soybean including main, epistatic, and QTL * environment effects in different
      regions of Northeast China.
AB  - The objective here was to identify QTL underlying soybean protein content (PC),
      and to evaluate the additive and epistatic effects of the QTLs. A mapping
      population, consisting of 129 recombinant inbred lines (RILs), was created by
      crossing 'Dongnong 46' and 'L-100'. Phenotypic data of the parents and RILs were
      collected for 4 years in three locations of Heilongjiang Province of China. A
      total of 213 SSR markers were used to construct a genetic linkage map. Eight
      QTLs, located on seven chromosomes (Chr), were identified to be associated with
      PC among the 10 tested environments. Of the seven QTLs, five QTLs, qPR-2
      (Satt710, on Chr9), qPR-3 (Sat_122, on Chr12), qPR-5 (Satt543, on Chr17), qPR-7
      (Satt163, on Chr18), and qPR-8 (Satt614, on Chr20), were detected in six, seven,
      seven, six, and seven environments, respectively, implying relatively stable
      QTLs. qPR-3 could explain 3.33%-11.26% of the phenotypic variation across eight
      tested environments. qPR-5 and qPR-8 explained 3.64%-10.1% and 11.86%-18.40% of
      the phenotypic variation, respectively, across seven tested environments. Eight
      QTLs associated with PC exhibited additive and (or) additive * environment
      interaction effects. The results showed that environment-independent QTLs often
      had higher additive effects. Moreover, five epistatic pairwise QTLs were
      identified in the 10 environments.

PMID- 28445653
TI  - Describing the Mental Health Profile of First Responders: A Systematic Review
      [Formula: see text].
AB  - BACKGROUND: First responders (FRs) are responsible for providing multiple
      services during various critical events. Considering the frequency, nature, and
      intensity of duty-related traumatic exposures, the cumulative impact on FRs'
      mental health is of paramount importance. OBJECTIVES: The purpose of this
      systematic review was to describe how duty-related trauma exposure can affect the
      comprehensive mental health profile of FRs, including firefighters, emergency
      medical technicians, and paramedics. DESIGN: Using Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines, a literature search was
      conducted using keywords related to FRs and mental health. RESULTS: Twenty-seven
      data-based articles met eligibility criteria and were included in this systematic
      review. Studies explored various mental health concerns, including posttraumatic
      stress disorder, depression, suicidality, anxiety, alcohol use, and sleep
      disturbances. CONCLUSIONS: Findings pose significant implications for psychiatric
      nurses in practice and research, including the need for tailored strategies to
      meet the mental health needs of this at-risk population.

PMID- 28445654
TI  - Gene editing and the health of future generations.

PMID- 28445655
TI  - Why gene editing isn't the answer.

PMID- 28445656
TI  - Learning What We Didn't Know - The SPRINT Data Analysis Challenge.

PMID- 28445657
TI  - Aquatic Bird Bornavirus-Associated Disease in Free-Living Canada Geese ( Branta
      canadensis ) in the Northeastern USA.
AB  - During the winter of 2013-14, 22 Canada geese ( Branta canadensis ) were admitted
      to the Wildlife Clinic at the Cummings School of Veterinary Medicine at Tufts
      University with nonspecific neurologic abnormalities and emaciation. Five of
      these geese, along with three geese that were submitted dead, were evaluated via
      histopathology, immunohistochemistry, and reverse transcription PCR (RT-PCR) for
      bornaviruses. Histopathologically, six of the eight birds had lymphoplasmacytic
      encephalitis. One bird, which also had encephalitis, had a dilated esophagus.
      Lead poisoning, West Nile virus, avian influenza, and avian paramyxovirus
      infection were excluded from the diagnosis. Brain tissue from all eight geese was
      positive for bornaviral N-antigen on immunohistochemistry. Frozen brain tissue
      from five birds was available for bornavirus RT-PCR. Three of the five birds were
      positive for the bornavirus M gene. Formalin-fixed paraffin-embedded brain tissue
      was evaluated on the remaining three geese via RT-PCR, with one of these geese
      testing positive. A bornavirus was subsequently cultured in duck embryo
      fibroblasts from the brain of one Canada Goose. This virus genome was sequenced,
      and the virus was identified as aquatic bird bornavirus 1. We were unable to
      identify any unusual features of this genome that would account for its apparent
      pathogenicity, given that subclinical infection with bornavirus in waterfowl is
      common in North America.

PMID- 28445658
TI  - A time and a place for everything: phylogenetic history and geography as joint
      predictors of oak plastome phylogeny.
AB  - Owing to high rates of introgressive hybridization, the plastid genome is poorly
      suited to fine-scale DNA barcoding and phylogenetic studies of the oak genus
      (Quercus, Fagaceae). At the tips of the oak plastome phylogeny, recent gene
      migration and reticulation generally cause topology to reflect geographic
      structure, while deeper branches reflect lineage divergence. In this study, we
      quantify the simple and partial effects of geographic proximity and nucleome
      inferred phylogenetic history on oak plastome phylogeny at different evolutionary
      scales. Our study compares pairwise phylogenetic distances based on complete
      plastome sequences, pairwise phylogenetic distances from nuclear restriction site
      associated DNA sequences (RADseq), and pairwise geographic distances for 34
      individuals of the white oak clade representing 24 North American and Eurasian
      species. Within the North American white oak clade alone, phylogenetic history
      has essentially no effect on plastome variation, while geography explains 11%-21%
      of plastome phylogenetic variance. However, across multiple continents and
      clades, phylogeny predicts 30%-41% of plastome variation, geography 3%-41%.
      Tipwise attenuation of phylogenetic informativeness in the plastome means that in
      practical terms, plastome data has little use in solving phylogenetic questions,
      but can still be a useful barcoding or phylogenetic marker for resolving
      questions among major clades.

PMID- 28445660
TI  - Spironolactone Metabolites in TOPCAT - New Insights into Regional Variation.

PMID- 28445661
TI  - Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

PMID- 28445659
TI  - Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis.
AB  - BACKGROUND: Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal
      antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA).
      We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis.
      METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial,
      we assessed the efficacy and safety of adalimumab in children and adolescents 2
      years of age or older who had active JIA-associated uveitis. Patients who were
      taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to
      receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight)
      or placebo, administered subcutaneously every 2 weeks. Patients continued the
      trial regimen until treatment failure or until 18 months had elapsed. They were
      followed for up to 2 years after randomization. The primary end point was the
      time to treatment failure, defined according to a multicomponent intraocular
      inflammation score that was based on the Standardization of Uveitis Nomenclature
      criteria. RESULTS: The prespecified stopping criteria were met after the
      enrollment of 90 of 114 patients. We observed 16 treatment failures in 60
      patients (27%) in the adalimumab group versus 18 treatment failures in 30
      patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval
      [CI], 0.12 to 0.49; P<0.0001 [the prespecified stopping boundary]). Adverse
      events were reported more frequently in patients receiving adalimumab than in
      those receiving placebo (10.07 events per patient-year [95% CI, 9.26 to 10.89]
      vs. 6.51 events per patient-year [95% CI, 5.26 to 7.77]), as were serious adverse
      events (0.29 events per patient-year [95% CI, 0.15 to 0.43] vs. 0.19 events per
      patient-year [95% CI, 0.00 to 0.40]). CONCLUSIONS: Adalimumab therapy controlled
      inflammation and was associated with a lower rate of treatment failure than
      placebo among children and adolescents with active JIA-associated uveitis who
      were taking a stable dose of methotrexate. Patients who received adalimumab had a
      much higher incidence of adverse events and serious adverse events than those who
      received placebo. (Funded by the NIHR Health Technology Assessment Programme and
      Arthritis Research UK; SYCAMORE EudraCT number, 2010-021141-41 .).

PMID- 28445662
TI  - Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

PMID- 28445663
TI  - Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

PMID- 28445664
TI  - Beyond Genes and Molecules - A Precision Delivery Initiative for Precision
      Medicine.

PMID- 28445665
TI  - Case 13-2017. A 41-Year-Old Man with Hearing Loss, Seizures, Weakness, and
      Cognitive Decline.

PMID- 28445667
TI  - Physical Abuse of Children.

PMID- 28445666
TI  - Stabilizing the Mixed Lineage Leukemia Protein.

PMID- 28445668
TI  - Adalimumab in the Treatment of Uveitis in Juvenile Idiopathic Arthritis.

PMID- 28445669
TI  - Challenges for Small Biopharmaceutical Companies.

PMID- 28445670
TI  - Challenges for Small Biopharmaceutical Companies.

PMID- 28445671
TI  - Pyogenic Granuloma of the Conjunctiva.

PMID- 28445672
TI  - A BAFFling Association between Malaria Resistance and the Risk of Multiple
      Sclerosis.

PMID- 28445673
TI  - Extramammary Paget's Disease.

PMID- 28445674
TI  - Hypothermia after In-Hospital Cardiac Arrest in Children.

PMID- 28445675
TI  - Hypothermia after In-Hospital Cardiac Arrest in Children.

PMID- 28445676
TI  - Board Review and the Middle-Aged Doctor.

PMID- 28445678
TI  - Author Response.

PMID- 28445679
TI  - Response to "A Comprehensive Nutrition-Focused Quality Improvement Program
      Reduces 30-Day Readmissions and Length of Stay in Hospitalized Patients".

PMID- 28445680
TI  - JPEN Journal Club 27: Vested Interests.

PMID- 28445681
TI  - Restoring the Microbiome in Critically Ill Patients: Are Probiotics Our True
      Friends When We Are Seriously Ill?

PMID- 28445682
TI  - Atrial Fibrillation: Diagnostic Accuracy of Coronary CT Angiography Performed
      with a Whole-Heart 230-um Spatial Resolution CT Scanner.
AB  - Purpose To assess image quality, interpretability, diagnostic accuracy, and
      radiation exposure of a computed tomography (CT) scanner with 16-cm coverage and
      230-um spatial resolution at coronary artery evaluation in patients with atrial
      fibrillation (AF) by using invasive coronary angiography (ICA) as the reference
      method and to compare the results with those obtained in patients with sinus
      rhythm (SR). Materials and Methods Written informed consent and institutional
      ethics committee approval were obtained. Between March 2015 and February 2016,
      166 consecutive patients were prospectively enrolled (83 with AF, 83 with SR).
      They underwent ICA and coronary CT angiography performed with a whole-heart CT
      scanner. Image quality, coronary segment interpretability, effective dose (ED),
      and diagnostic accuracy were assessed at CT angiography and were compared with
      those attained with ICA. Diagnostic performance of the groups was compared with
      the pairwise McNemar test. Results Mean heart rate during scanning was 83 beats
      per minute +/- 21 (standard deviation) in the AF group and 63 beats per minute +/
      14 in the SR group (P < .01). Coronary interpretability was 98.5% in the AF
      group and 98.4% in the SR group (P = .96). In a segment-based analysis,
      sensitivity and specificity in the detection of coronary stenosis of more than
      50% compared with detection of ICA were 96.4% and 98.7%, respectively, in the
      chronic AF group (P = .98) and 95.6% and 98.1%, respectively, in the SR group (P
      = .32). In a patient-based analysis, sensitivity and specificity were 95.2% and
      97.6%, respectively, in the chronic AF group (P = .95) and 97.8% and 94.7%,
      respectively, in the SR group (P = .93). Conclusion Whole-heart CT enables
      evaluation of coronary arteries with high image quality, low radiation exposure,
      and high diagnostic accuracy in patients with chronic AF, with a diagnostic
      performance similar to that in patients with SR. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 28445677
TI  - Overexpression of the Cytokine BAFF and Autoimmunity Risk.
AB  - BACKGROUND: Genomewide association studies of autoimmune diseases have mapped
      hundreds of susceptibility regions in the genome. However, only for a few
      association signals has the causal gene been identified, and for even fewer have
      the causal variant and underlying mechanism been defined. Coincident associations
      of DNA variants affecting both the risk of autoimmune disease and quantitative
      immune variables provide an informative route to explore disease mechanisms and
      drug-targetable pathways. METHODS: Using case-control samples from Sardinia,
      Italy, we performed a genomewide association study in multiple sclerosis followed
      by TNFSF13B locus-specific association testing in systemic lupus erythematosus
      (SLE). Extensive phenotyping of quantitative immune variables, sequence-based
      fine mapping, cross-population and cross-phenotype analyses, and gene-expression
      studies were used to identify the causal variant and elucidate its mechanism of
      action. Signatures of positive selection were also investigated. RESULTS: A
      variant in TNFSF13B, encoding the cytokine and drug target B-cell activating
      factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease
      risk allele was also associated with up-regulated humoral immunity through
      increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal
      variant was identified: an insertion-deletion variant, GCTGT->A (in which A is
      the risk allele), yielded a shorter transcript that escaped microRNA inhibition
      and increased production of soluble BAFF, which in turn up-regulated humoral
      immunity. Population genetic signatures indicated that this autoimmunity variant
      has been evolutionarily advantageous, most likely by augmenting resistance to
      malaria. CONCLUSIONS: A TNFSF13B variant was associated with multiple sclerosis
      and SLE, and its effects were clarified at the population, cellular, and
      molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and
      others.).

PMID- 28445684
TI  - Patient, staffing and health centre factors associated with annual testing for
      sexually transmissible infections in remote primary health centres.
AB  - BACKGROUND: In high-incidence Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (NG) settings, annual re-testing is an important public health
      strategy. Using baseline laboratory data (2009-10) from a cluster randomised
      trial in 67 remote Aboriginal communities, the extent of re-testing was
      determined, along with the associated patient, staffing and health centre
      factors. METHODS: Annual testing was defined as re-testing in 9-15 months
      (guideline recommendation) and a broader time period of 5-15 months following an
      initial negative CT/NG test. Random effects logistic regression was used to
      determine factors associated with re-testing. RESULTS: Of 10559 individuals aged
      >=16 years with an initial negative CT/NG test (median age=25 years), 20.3% had a
      re-test in 9-15 months (23.6% females vs 15.4% males, P<0.001) and 35.2% in 5-15
      months (40.9% females vs 26.5% males, P<0.001). Factors independently associated
      with re-testing in 9-15 months in both males and females were: younger age (16
      19, 20-24 years); and attending a centre that sees predominantly (>90%)
      Aboriginal people. Additional factors independently associated with re-testing
      for females were: being aged 25-29 years, attending a centre that used electronic
      medical records, and for males, attending a health centre that employed
      Aboriginal health workers and more male staff. CONCLUSIONS: Approximately 20% of
      people were re-tested within 9-15 months. Re-testing was more common in younger
      individuals. Findings highlight the importance of recall systems, Aboriginal
      health workers and male staff to facilitate annual re-testing. Further
      initiatives may be needed to increase re-testing.

PMID- 28445683
TI  - Impact of Preoperative Breast MR Imaging and MR-guided Surgery on Diagnosis and
      Surgical Outcome of Women with Invasive Breast Cancer with and without DCIS
      Component.
AB  - Purpose To (a) compare the diagnostic accuracy of breast magnetic resonance (MR)
      imaging with that of conventional imaging (digital mammography and breast
      ultrasonography) in the identification of ductal carcinoma in situ (DCIS)
      components of biopsy-proven invasive breast cancer before surgery and (b)
      investigate the surgical outcome (positive margin rates and mastectomy rates) of
      women with breast cancer who underwent preoperative MR imaging combined with MR
      guided needle biopsy and/or MR-guided lesion localization or bracketing where
      appropriate. Materials and Methods The authors performed a prospective two-center
      study of 593 consecutive patients with biopsy-proven invasive breast cancer who
      underwent breast MR imaging in addition to conventional imaging. MR-guided vacuum
      biopsy and MR-guided lesion bracketing were performed for DCIS components visible
      at MR imaging alone. The accuracy of breast MR imaging was compared with that of
      conventional imaging, and surgical outcomes (positive margin and mastectomy
      rates) were investigated. Results Surgical-pathologic assessment demonstrated
      DCIS components in 139 of the 593 women (23.4%). The sensitivity of MR imaging
      for the diagnosis of DCIS components pre-operatively (84.9%; 118 of 139) was
      significantly higher than that of conventional imaging (36.7%; 51 of 139) (P <
      .0001); more than half of DCIS components (51.1%; 71 of 139) were detected only
      with MR imaging. The sensitivity advantage of MR imaging over conventional
      imaging increased with increasing relative size of DCIS components, as follows:
      The sensitivity of MR imaging versus conventional imaging for small, marginal
      DCIS components was 56.8% (21 of 37) versus 29.7% (11 of 37); the sensitivity for
      extensive DCIS components was 91.7% (55 of 60) versus 41.7% (25 of 60); the
      sensitivity for large, predominant DCIS components was 100.0% (42 of 42) versus
      35.7% (15 of 42). Moreover, the sensitivity advantage of MR imaging over
      conventional imaging increased with increasing nuclear grade of DCIS components,
      as follows: The sensitivity of MR imaging versus conventional imaging for low
      grade DCIS components was 74.0% (20 of 27) versus 40.7% (11 of 27); the
      sensitivity for intermediate-grade DCIS components was 84.1% (53 of 63) versus
      34.9% (22 of 63); the sensitivity for high-grade DCIS components was 91.8% (45 of
      49) versus 36.7% (18 of 49) (P < .05-.001 for all). Positive margin rates were
      low overall (3.7% [95% Clopper Pearson confidence interval [CI]: 2.3%, 5.6%]) and
      did not differ significantly between the 139 women with DCIS components (5.0%
      [95% CI: 2.0%, 10.1%]) compared with the 454 women without such components (3.3%
      [95% CI: 1.9%, 5.4%]). The same was true for mastectomy rates (10.8% [95% CI:
      6.2%, 17.2%] vs 8.1% [95% CI: 5.8%, 11.1%]). Conclusion Breast MR imaging
      improves depiction of DCIS components of invasive breast cancers before surgery
      and is associated with positive margin and mastectomy rates that are low
      irrespective of the presence or absence of DCIS components. (c) RSNA, 2017.

PMID- 28445685
TI  - Outcomes following detection of low level plasma HIV RNA in HIV-infected patients
      previously virologically suppressed on antiretroviral therapy: a retrospective
      observational study.
AB  - BACKGROUND: Progressively sensitive assays for plasma HIV RNA have led to
      increased detection of plasma HIV RNA between 20 and 200 copies/ml, known as low
      level viremia (LLV) when recurrent or persistent, in HIV-infected patients on
      antiretroviral therapy (ART). The aim of this study was to determine outcomes
      following initial detection of LLV in an Australian cohort. METHODS: A
      retrospective study using the HIV Service Database (Alfred Hospital) included all
      patients on ART who recorded plasma HIV RNA 20-200 copies/mL following prior
      virological suppression (viral load (VL) HIV RNA <20 copies/mL) over 2 years
      (2010 to 2012), with follow-up to June 2013. Factors associated with subsequent
      virological outcome were assessed via univariate and multivariate analysis.
      RESULTS: Of 919 patients managed by The Alfred HIV service, 207 (22.5%) met
      inclusion criteria. Mean age was 48.8 years, 91.3% were male. During follow-up,
      54% patients recorded no further HIV RNA 20-200 copies/mL (viral blip); 39% had
      recurrent or persistent VL 20-200 copies/mL (LLV); and 7% progressed to
      virological failure with VL >200 copies/mL. Factors associated with LLV included
      co-morbid type 2 diabetes, shorter prior virological suppression and lower nadir
      CD4 cell count. Clinician management of VL 20-200 copies/mL was generally
      conservative, with infrequent requests for genotypic analysis (3.3% cases) or
      change in ART (<1% cases). CONCLUSIONS: LLV following virological suppression is
      common, and occurred as an isolated viral blip in half the patients. Those
      patients with persistent or recurrent LLV had higher rates of type 2 diabetes,
      shorter prior virological suppression and lower nadir CD4 cell count.

PMID- 28445686
TI  - When a relationship is imperative, will young women knowingly place their sexual
      health at risk? A sample of African American adolescent girls in the juvenile
      justice system.
AB  - BACKGROUND: HIV and other sexually transmissible infections (HIV/STIs) are
      significant contributors to adolescent girls' morbidity in the US. Risks for
      HIV/STIs are increased among adolescent girls involved in the juvenile justice
      system, and African American adolescent girls comprise nearly 50% of adolescent
      girls in detention centres. Although HIV prevention programs focus on HIV/STI
      knowledge, increased knowledge may not be sufficient to reduce sexual risk. The
      present study examined the interactive effects of HIV/STI knowledge and the
      importance of being in a relationship (a relationship imperative) on sexual risk
      behaviours in a sample of detained African American adolescent girls. METHODS: In
      all, 188 African American adolescent girls, 13-17 years of age, were recruited
      from a short-term detention facility in Atlanta, Georgia, and completed
      assessments on sexual risk behaviours, relationship characteristics, HIV/STI
      knowledge and several psychosocial risk factors. RESULTS: When girls endorsed a
      relationship imperative, higher HIV/STI knowledge was associated with low partner
      communication self-efficacy, inconsistent condom use and unprotected sex, when
      controlling for demographics and self-esteem. CONCLUSIONS: Young girls with high
      HIV/STI knowledge may have placed themselves at risk for HIV/STIs given the
      importance and value they place on being in a relationship. Contextual factors
      should be considered when developing interventions.

PMID- 28445687
TI  - Accuracy of low dose CT in the diagnosis of appendicitis in childhood and
      comparison with USG and standard dose CT.
AB  - OBJECTIVES: Computed tomography should be performed after careful consideration
      due to radiation hazard, which is why interest in low dose CT has increased
      recently in acute appendicitis. Previous studies have been performed in adult and
      adolescents populations, but no studies have reported on the efficacy of using
      low-dose CT in children younger than 10 years. METHODS: Patients (n=475) younger
      than 10 years who were examined for acute appendicitis were recruited. Subjects
      were divided into three groups according to the examinations performed: low-dose
      CT, ultrasonography, and standard-dose CT. Subjects were categorized according to
      age and body mass index (BMI). RESULTS: Low-dose CT was a contributive tool in
      diagnosing appendicitis, and it was an adequate method, when compared with
      ultrasonography and standard-dose CT in terms of sensitivity (95.5% vs. 95.0% and
      94.5%, p=0.794), specificity (94.9% vs. 80.0% and 98.8%, p=0.024), positive
      predictive value (96.4% vs. 92.7% and 97.2%, p=0.019), and negative-predictive
      value (93.7% vs. 85.7% and 91.3%, p=0.890). Low-dose CT accurately diagnosed
      patients with a perforated appendix. Acute appendicitis was effectively diagnosed
      using low-dose CT in both early and middle childhood. BMI did not influence the
      accuracy of detecting acute appendicitis on low-dose CT. CONCLUSION: Low-dose CT
      is effective and accurate for diagnosing acute appendicitis in childhood, as well
      as in adolescents and young adults. Additionally, low-dose CT was relatively
      accurate, irrespective of age or BMI, for detecting acute appendicitis.
      Therefore, low-dose CT is recommended for assessing children with suspected acute
      appendicitis.

PMID- 28445688
TI  - Resting-state functional connectivity of the amygdala in suicide attempters with
      major depressive disorder.
AB  - In this study, we investigated the difference in resting-state functional
      connectivity (RSFC) of the amygdala between suicide attempters and non-suicide
      attempters with major depressive disorder (MDD) using functional magnetic
      resonance imaging (fMRI). This study included 19 suicide attempters with MDD and
      19 non-suicide attempters with MDD. RSFC was compared between the two groups and
      the regression analyses were conducted to identify the correlation between RSFC
      and Scale for Suicide Ideation (SSI) scores in the suicide attempt group.
      Statistical significance was set at p-value (uncorrected) <0.005 with k>=28
      voxels. Compared with non-suicide attempters, suicide attempters showed
      significantly increased RSFC of the left amygdala with the right insula and left
      superior orbitofrontal area, and increased RSFC of the right amygdala with the
      left middle temporal area. The regression analysis showed a significant
      correlation between the SSI total score and RSFC of the right amygdala with the
      right parahippocampal area in the suicide attempt group. The present RSFC
      findings provide evidence of a functional neural basis and will help reveal the
      pathophysiology underlying suicidality in subjects with MDD.

PMID- 28445689
TI  - Clinical staging and serum cytokines in bipolar patients during euthymia.
AB  - AIMS: Changes in serum cytokines and altered neutrophin concentration have been
      associated with bipolar disorder (BD). Our aim here was to analyze peripheral
      blood biomarkers according to the clinical stages of BD. METHOD: Euthymic BD-I
      patients were grouped according to their level of functioning in early-stage
      (n=25) and late-stage (n=23), and compared to healthy siblings (n=23) and
      genetically unrelated healthy controls (n=21). Neurotrophin (neurotrophin-3 and
      BDNF) concentration and biomarkers of inflammation, including cytokines (IL-6, IL
      10 and TNF-alpha), leukocytes count and acute phase proteins, were measured.
      RESULTS: IL-10 concentration was significantly increased in early-stage patients
      compared to late-stage patients, healthy siblings and controls whereas TNF-alpha
      concentration was significantly increased in late-stage patients compared to
      controls. Total leukocytes, neutrophil and monocyte count were significantly
      increased in late-stage patients compared to healthy siblings and controls. The
      concentration of IL-6, neurotrophin-3 and BDNF was unchanged in euthymia. Healthy
      siblings did not show significant changes in any biomarker. CONCLUSIONS: The
      concentration of IL-10, TNF-alpha, neutrophil and monocytes subtype count in
      blood is altered in patients with BD during euthymic state. The link between
      peripheral inflammation and different stages in BD deserves further studies.

PMID- 28445690
TI  - Effect of antidepressant treatment on peripheral inflammation markers - A meta
      analysis.
AB  - INTRODUCTION: Major Depressive Disorder (MDD) in accordance to the inflammatory
      concept is associated with complex immunological disturbances in the central
      nervous system (CNS). This is reflected by elevated plasma levels of inflammatory
      cytokines in depressed subjects. Although numerous studies report significant
      influence of antidepressants on pro-inflammatory/anti-inflammatory cytokines
      balance, the available data is often inconsistent regarding specific cytokines
      and drugs used. We aimed to perform a comprehensive meta-analysis of the effect
      of antidepressant treatment on a wide array of cytokines. METHODS: We performed a
      systematic search of 6 databases, which yielded 32 studies measuring the levels
      of selected cytokines before and at a second time-point during antidepressant
      treatment. For meta-analysis of selected studies with a continuous measure we
      analysed variables containing the number of cases, mean and standard deviation of
      the level of IL-1beta, IL-2, IL-5, IL-6, IL-8, IL-10, CRP, TNF-alpha, IFN-gamma
      levels observed in the different studies, in the intervention groups before and
      after antidepressant treatment. RESULTS: Statistical analysis revealed
      significant decreases of IL-4, IL-6, and IL-10 in MDD subjects after
      antidepressant treatment. In case of IL-1beta the decrease was significant
      exclusively for SSRI drugs. We did not find any significant effect of
      antidepressant medication on IL-2, TNF-alpha IFN-gamma and CRP. CONCLUSIONS:
      Antidepressant treatment affects the levels of cytokines in depression. The
      immunological imbalance in MDD is complex and seems to be mediated by other
      factors yet to be elucidated. The credibility of our results is limited by high
      heterogeneity among studies and very few studies with a placebo-controlled
      design. Research with MDD subtypes, response to treatment status and cytokine
      associations with the kynurenine pathway taken into account pose a promising
      target for future studies.

PMID- 28445692
TI  - Perspectives on testicular sex cord-stromal tumors and those composed of both
      germ cells and sex cord-stromal derivatives with a comparison to corresponding
      ovarian neoplasms.
AB  - Sex cord-stromal tumors (SCSTs) are the second most frequent category of
      testicular neoplasms, accounting for approximately 2% to 5% of cases. Both
      genetic and epigenetic factors account for the differences in frequency and
      histologic composition between testicular and ovarian SCSTs. For example, large
      cell calcifying Sertoli cell tumor and intratubular large cell hyalinizing
      Sertoli cell neoplasia occur in the testis but have not been described in the
      ovary. In this article, we discuss recently described diagnostic entities as well
      as inconsistencies in nomenclature used in the recent World Health Organization
      classifications of SCSTs in the testis and ovary. We also thoroughly review the
      topic of neoplasms composed of both germ cells and sex cord derivatives with an
      emphasis on controversial aspects. These include "dissecting gonadoblastoma" and
      testicular mixed germ cell-sex cord stromal tumor (MGC-SCST). The former is a
      recently described variant of gonadoblastoma that sometimes is an immediate
      precursor of germinoma in the dysgenetic gonads of patients with a disorder of
      sex development. Although the relationship of dissecting gonadoblastoma to the
      previously described undifferentiated gonadal tissue is complex and not entirely
      resolved, we believe that it is preferable to continue to use the term
      undifferentiated gonadal tissue for those cases that are not neoplastic and are
      considered to be the precursor of classical gonadoblastoma. Although the
      existence of testicular MGC-SCST has been challenged, the most recent evidence
      supports its existence; however, testicular MGC-SCST differs significantly from
      ovarian examples due to both genetic and epigenetic factors.

PMID- 28445691
TI  - Tis11 mediated mRNA decay promotes the reacquisition of Drosophila intestinal
      stem cell quiescence.
AB  - Adult stem cell proliferation rates are precisely regulated to maintain long-term
      tissue homeostasis. Defects in the mechanisms controlling stem cell proliferation
      result in impaired regeneration and hyperproliferative diseases. Many stem cell
      populations increase proliferation in response to tissue damage and reacquire
      basal proliferation rates after tissue repair is completed. Although
      proliferative signals have been extensively studied, much less is known about the
      molecular mechanisms that restore stem cell quiescence. Here we show that Tis11,
      an Adenine-uridine Rich Element (ARE) binding protein that promotes mRNA
      degradation, is required to re-establish basal proliferation rates of adult
      Drosophila intestinal stem cells (ISC) after a regenerative episode. We find that
      Tis11 limits ISC proliferation specifically after proliferation has been
      stimulated in response to heat stress or infection, and show that Tis11
      expression and activity are increased in ISCs during tissue repair. Based on stem
      cell transcriptome analysis and RNA immunoprecipitation, we propose that Tis11
      activation represents an integral part of a negative feedback mechanism that
      limits the expression of key components of several signaling pathways that
      control ISC function and proliferation. Our results identify Tis11 mediated mRNA
      decay as an evolutionarily conserved mechanism of re-establishing basal
      proliferation rates of stem cells in regenerating tissues.

PMID- 28445693
TI  - High-content analysis screening for cell cycle regulators using arrayed synthetic
      crRNA libraries.
AB  - The CRISPR-Cas9 system has been utilized for large-scale, loss-of-function
      screens mainly using lentiviral pooled formats and cell-survival phenotypic
      assays. Screening in an arrayed format expands the types of phenotypic readouts
      that can be used to now include high-content, morphology-based assays, and with
      the recent availability of synthetic crRNA libraries, new studies are emerging.
      Here, we use a cell cycle reporter cell line to perform an arrayed, synthetic
      crRNA:tracrRNA screen targeting 169 genes (>600 crRNAs) and used high content
      analysis (HCA) to identify genes that regulate the cell cycle. Seven parameters
      were used to classify cells into cell cycle categories and multiple parameters
      were combined using a new analysis technique to identify hits. Comprehensive hit
      follow-up experiments included target gene expression analysis, confirmation of
      DNA insertions/deletions, and validation with orthogonal reagents. Our results
      show that most hits had three or more independent crRNAs per gene that
      demonstrated a phenotype with consistent individual parameters, indicating that
      our screen produced high-confidence hits with low off-target effects and allowed
      us to identify hits with more subtle phenotypes. The results of our screen
      demonstrate the power of using arrayed, synthetic crRNAs for functional
      phenotypic screening using multiparameter HCA assays.

PMID- 28445694
TI  - Work first then play: Prior task difficulty increases motivation-related brain
      responses in a risk game.
AB  - Task motivation depends on what we did before. A recent theory differentiates
      between tasks that we want to do and tasks that we have to do. After a have-to
      task, motivation shifts towards a want-to task. We measured this shift of
      motivation via brain responses to monetary feedback in a risk game that was used
      as want-to task in our study. We tested 20 healthy participants that were about
      28 years old in a within-subjects design. Participants worked on a Stroop task
      (have-to task) or an easier version of the Stroop task as a control condition and
      played a risk game afterwards (want-to task). After the Stroop task, brain
      responses to monetary feedback in the risk game were larger compared to the
      easier control task, especially for feedback indicating higher monetary rewards.
      We conclude that higher amplitudes of feedback-related brain responses in the
      risk game reflect the shift of motivation after a have-to task towards a want-to
      task.

PMID- 28445695
TI  - Neural correlates of evoked phantom limb sensations.
AB  - Previous work showed the existence of changes in the topographic organization
      within the somatosensory cortex (SI) in amputees with phantom limb pain, however,
      the link between nonpainful phantom sensations such as cramping or tingling or
      the percept of the limb and cortical changes is less clear. We used functional
      magnetic resonance imaging (fMRI) in a highly selective group of limb amputees
      who experienced inducible and reproducible nonpainful phantom sensations. A
      standardized procedure was used to locate body sites eliciting phantom sensations
      in each amputee. Selected body sites that could systematically evoke phantom
      sensations were stimulated using electrical pulses in order to induce phasic
      phantom sensations. Homologous body parts were also stimulated in a group of
      matched controls. Activations related to evoked phantom sensations were found
      bilaterally in SI and the intraparietal sulci (IPS), which significantly
      correlated with the intensity of evoked phantom sensations. In addition, we found
      differences in intra- and interhemispheric interaction between amputees and
      controls during evoked phantom sensations. We assume that phantom sensations
      might be associated with a functional decoupling between bilateral SI and IPS,
      possibly resulting from transcallosal reorganization mechanisms following
      amputation.

PMID- 28445696
TI  - Which Factors Affect Citation Rates in the Oral and Maxillofacial Surgery
      Literature?
AB  - PURPOSE: Citation rate is one of several tools to measure academic productivity.
      The purposes of this study were to estimate and identify factors associated with
      citation rates in the oral and maxillofacial surgery (OMS) literature. MATERIALS
      AND METHODS: This was a retrospective longitudinal study of publications in the
      Journal of Oral and Maxillofacial Surgery (JOMS), International Journal of Oral
      and Maxillofacial Surgery (IJOMS), and Oral Surgery, Oral Medicine, Oral
      Pathology, and Oral Radiology (OOOO) from January through December 2012. The
      predictor variables were author- and article-specific factors. The outcome
      variable was the citation rate, defined as the total number of citations for each
      article over a 4-year period. Descriptive, bivariate, and multiple regression
      statistics were computed. RESULTS: The authors identified 993 articles published
      during 2012. The mean number of citations at 4 years after publication was 5.6 +/
      5.3 (median, 4). In bivariate analyses, several author- and article-specific
      factors were associated with citation rates. In a multiple regression model
      adjusting for potential confounders and effect modifiers, first author H-index,
      number of authors, journal, OMS focus area, and Oxford level of evidence were
      significantly associated with citation rate (P <= .002). CONCLUSION: The authors
      identified 5 factors associated with citation rates in the OMS literature. These
      factors should be considered in context when evaluating citation-based metrics
      for OMS. Studies that focus on core OMS procedures (eg, dentoalveolar surgery,
      dental implant surgery), are published in specialty-specific journals (eg, JOMS
      or IJOMS), and have higher levels of evidence are more likely to be cited.

PMID- 28445697
TI  - Influence of Maturation on In Vivo Tissue to Plasma Partition Coefficients for
      Cis- and Trans-Permethrin.
AB  - Permethrin, the most widely used household insecticide in the United States, is
      marketed as a mixture of its cis (CIS) and trans (TRANS) isomers. The major
      objective of this investigation is to develop and utilize a reliable approach to
      determine in vivo partition coefficients (PCs) for CIS and TRANS in immature and
      adult Sprague-Dawley rats. Adult, postnatal day (PND) 21, and PND 15 rats were
      infused with environmentally relevant concentrations of CIS or TRANS via a
      subcutaneous osmotic pump for 48 or 72 h. The adult and PND 21 rats also received
      an oral loading dose. Systemic steady-state or equilibrium was attained in each
      age group within 72 h of the protocol. CIS and TRANS were both distributed to
      tissues according to their neutral lipid content, with adipose tissue exhibiting
      much higher tissue:plasma PCs than skeletal muscle, liver, or brain. Liver:plasma
      and brain:plasma PCs were consistently at or lower than unity. Tissue:plasma PCs
      were generally higher for CIS than for TRANS, although the isomers are of
      comparable lipophilicity. Significantly higher blood levels of CIS apparently
      saturate plasma binding, resulting in greater tissue deposition of the isomer.
      CIS and TRANS tissue:plasma PCs were found to be inversely related to the rats'
      age, although TRANS brain:plasma PCs were comparable in immature and mature
      animals. These data support the conclusion that age-dependent partitioning is an
      important determinant of the pharmacokinetics of permethrin. Such partitioning
      could influence the risk assessment of these insecticides in infants and children
      when incorporated into physiologically based pharmacokinetic models.

PMID- 28445698
TI  - Editorial: DNA damage & immunity.

PMID- 28445699
TI  - Journey of cystatins from being mere thiol protease inhibitors to at heart of
      many pathological conditions.
AB  - Cystatins are thiol proteinase inhibitors (TPI), present ubiquitously in animals,
      plants and micro-organisms. These are not merely inhibitors rather they are at
      heart of many pathological conditions ranging from diabetes to renal failure.
      These are essential for maintenance of protein balance of the cell; once this
      balance gets disturbed, it may lead to cell death. Thus, cystatins cannot be
      merely regarded as TPI's as these have been found to play a pivotal role in
      tumorigenesis and neurodegenerative diseases. Many studies have reported the
      variation in cystatin level in incidences of different types of cancer;
      highlighting an important role played by these inhibitors in cancer development
      and progression. Cystatin C is increasingly replacing creatinine as a biomarker
      of glomerular filtration rate (GFR) thereby highlighting the importance of this
      important inhibitor. Some recent studies have also reported the interaction
      pattern of various anti-cancer drugs with cystatins in a bid to find how these
      drugs affect this important inhibitors and whether these drugs have any side
      effect on cystatins. Thus, in this growing disease era it can be said that
      cystatins are no more just inhibitors blocking the activity of thiol proteases
      rather they play a pivotal role in variety of pathological conditions.

PMID- 28445700
TI  - Design, synthesis of novel chitosan derivatives bearing quaternary phosphonium
      salts and evaluation of antifungal activity.
AB  - Two novel chitosan derivatives modified with quaternary phosphonium salts were
      successfully synthesized, including tricyclohexylphosphonium acetyl chitosan
      chloride (TCPACSC) and triphenylphosphonium acetyl chitosan chloride (TPPACSC),
      and characterized by FTIR, 1H NMR, and 13C NMR spectra. The degree of
      substitution was also calculated by elemental analysis results. Their antifungal
      activities against Colletotrichum lagenarium, Watermelon fusarium, and Fusarium
      oxysporum were investigated in vitro using the radial growth assay, minimal
      inhibitory concentration, and minimum bactericidal concentration assay. The
      fungicidal assessment revealed that the synthesized chitosan derivatives had
      superior antifungal activity compared with chitosan. Especially, TPPACSC
      exhibited the best antifungal property with inhibitory indices of over 75% at
      1.0mg/mL. The results obviously showed that quaternary phosphonium groups could
      effectively enhance antifungal activity of the synthesized chitosan derivatives.
      Meanwhile, it was also found that their antifungal activity was influenced by
      electron-withdrawing ability of the quaternary phosphonium salts. The synthetic
      strategy described here could be utilized for the development of chitosan as
      antifungal biomaterials.

PMID- 28445701
TI  - Prevalence, antimicrobial susceptibility and multiplex PCR-serotyping of Listeria
      monocytogenes isolated from humans, foods and livestock in Iran.
AB  - Listeria monocytogenes is a foodborne pathogen causing listeriosis, which
      potentially affects all individuals, especially pregnant women and
      immunocompromised persons. The present study investigated the prevalence,
      antimicrobial susceptibility and serotypes distribution of the isolated L.
      monocytogenes from Iran. Twenty two (4.97%) of 442 human, food and livestock
      samples were found to be positive for L. monocytogenes. L. monocytogenes was
      identified in 8.8% of 125 human samples, 2.99% of 267 food and 6% of 50 livestock
      samples. The standard disk diffusion method and minimum inhibitory concentration
      (MIC) assay were used for antimicrobial susceptibility testing and multiplex PCR
      for serotyping. Among the 22 isolates tested, 6 (27.2%) displayed resistance to
      penicillin G, with all of the isolates and 2 (9%) of them showing intermediate
      susceptibility to clindamycin and rifampicin, respectively. According to the MIC
      assay, the rate of resistance to penicillin G was the same as that of disk
      diffusion method, but 16 (72.7%) of isolates showed intermediate susceptibility
      to clindamycin using E-test. In the multiplex PCR, 19 (86.4%) of isolates
      belonged to serotype 1/2c or 3c and the remaining 3 isolates were identified as
      (4b, 4d or 4e) and (1/2a or 3a), respectively. The occurrence of resistance to
      penicillin G, which can be used in the treatment of listeriosis, is very alarming
      and more prevalence of 1/2c serotype, in comparison to 3 other important ones
      (1/2a, 1/2b and 4b), in Iran has been reported for the first time. To the best of
      our knowledge, this is the first study showing the distribution of various
      serogroups of L. monocytogenes from human and livestock in Iran.

PMID- 28445702
TI  - An Early History of Anesthesia in Labor.
AB  - Fear of pain often overshadows childbirth, and each woman must decide whether to
      receive anesthesia to combat labor pain. Historically, this choice resulted in
      unintended consequences and marked the beginnings of medical interventions in
      labor and birth. The purpose of this article is to trace the use of anesthesia in
      childbirth from the mid-19th to the mid-20th centuries and to explore its
      influence on childbearing women and nurses.

PMID- 28445703
TI  - Sensitivity and Specificity of Laser-Scanning In Vivo Confocal Microscopy for
      Filamentous Fungal Keratitis: Role of Observer Experience.
AB  - PURPOSE: To determine sensitivity and specificity of laser-scanning in vivo
      confocal microscopy (LS-IVCM) for detection of filamentous fungi in patients with
      microbial keratitis and to evaluate the effect of observer's imaging experience
      on these parameters. DESIGN: Retrospective reliability study. METHODS: This study
      included 21 patients with filamentous fungal keratitis and 24 patients with
      bacterial keratitis (as controls). The etiology of infection was confirmed based
      on the response to specific therapy regardless of culture results. All patients
      had undergone full-thickness corneal imaging by a LS-IVCM (Heidelberg Retina
      Tomograph 3 with Rostock Cornea Module; Heidelberg Engineering, Heidelberg,
      Germany). The images were evaluated for the presence of fungal filaments by 2
      experienced observers and 2 inexperienced observers. All observers were masked to
      the clinical and microbiologic data. RESULTS: The mean number of images obtained
      per eye was 917 +/- 353. The average sensitivity of LS-IVCM for detecting fungal
      filaments was 71.4% +/- 0% for the experienced observers and 42.9% +/- 6.7% for
      the inexperienced observers. The average specificity was 89.6% +/- 3.0% and 87.5%
      +/- 17.7% for these 2 groups of observers, respectively. Although there was a
      good agreement between the 2 experienced observers (kappa = 0.77), the
      inexperienced observers showed only a moderate interobserver agreement (kappa =
      0.51). The LS-IVCM sensitivity was higher in patients with fungal infections who
      had positive culture or longer duration of the disease. CONCLUSIONS: Although LS
      IVCM has a high specificity for diagnosing filamentous fungal keratitis, its
      sensitivity is moderate and highly dependent on the level of the observer's
      experience and training with this imaging modality.

PMID- 28445704
TI  - Development of standard methods for Zika virus propagation, titration, and
      purification.
AB  - The emergence of Zika virus (ZIKV) infection has stimulated several research
      groups to study and collaborate to understand virus biology and pathogenesis.
      These efforts may assist with the development of antiviral drugs, vaccines and
      diagnostic tests, as well as to promote advancements in public health policies.
      Here, we aim to develop standard protocols for propagation, titration, and
      purification of ZIKV strains, by systematically testing different cell types,
      kinetics, multiplicity of infection and centrifugation protocols. ZIKV produces a
      productive infection in human, non-human primate, and rodents-derived cell lines,
      with different efficacies. The highest yield of ZIKV-AFR and ZIKV-BR infectious
      progeny was obtained at 7days post infection in C6/36 cells (7*107 and 2*108
      PFU/ml, respectively). However, high titers of ZIKV-AFR could be obtained at
      earlier time points in Vero cells (2.5*107PFU/ml at 72hpi), whereas ZIKV-BR
      titers reached 108 PFU/ml at 4dpi in C6/36 cells. High yield of purified virus
      was obtained by purification through a discontinuous sucrose gradient. This
      optimized procedure will certainly contribute to future studies of virus
      structure and vaccine development. Beyond the achievement of efficient virus
      propagation, the normalization of these protocols will also allow different
      laboratories around the world to better compare and discuss data regarding
      different features of ZIKV biology and disease, contributing to more efficient
      collaborations and progression in ZIKV research.

PMID- 28445705
TI  - Mutation characterization and heterodimer analysis of patients with leukocyte
      adhesion deficiency: Including one novel mutation.
AB  - BACKGROUND AND AIM: Leukocyte adhesion deficiency type 1 (LAD-I) is a rare,
      autosomal recessive disorder of neutrophil migration, characterized by severe,
      recurrent bacterial infections, inadequate pus formation and impaired wound
      healing. The ITGB2 gene encodes the beta2 integrin subunit (CD18) of the
      leukocyte adhesion cell molecules, and mutations in this gene cause LAD-I. The
      aim of the current study was to investigate the mutations in patients diagnosed
      with LAD-I and functional studies of the impact of two previously reported and a
      novel mutation on the expression of the CD18/CD11a heterodimer. MATERIALS AND
      METHODS: Blood samples were taken from three patients who had signed the consent
      form. Genomic DNA was extracted and ITGB2 exons and flanking intronic regions
      were amplified by polymerase chain reaction. Mutation screening was performed
      after Sanger sequencing of PCR products. For functional studies, COS-7 cells were
      co-transfected with an expression vector containing cDNA encoding mutant CD18
      proteins and normal CD11a. Flow cytometry analysis of CD18/CD11a expression was
      assessed by dimer-specific IB4 monoclonal antibody. RESULTS: Two previously
      reported mutations and one novel mutation,p. Cys562Tyr, were found. All mutations
      reduced CD18/CD11 heterodimer expression. CONCLUSION: Our strategy recognized the
      p.Cys562Tyr mutation as a pathogenic alteration that does not support CD18
      heterodimer formation. Therefore, it can be put into a panel of carrier and
      prenatal diagnosis programs.

PMID- 28445706
TI  - Fabrication of electrochemical biosensor with vanadium pentoxide nano-interface
      for the detection of methylglyoxal in rice.
AB  - Increased consumption of raw and par-boiled rice results in the formation of
      methylglyoxal (MG) at higher concentration and leads to complications in diabetic
      patients. Highly sensitive electrochemical biosensor was developed using
      glutathione (GSH) as a co-factor with vanadium pentoxide (V2O5) as a nano
      interface for MG detection in rice samples. The Pt/V2O5/GSH/Chitosan bioelectrode
      displayed two well-defined redox peaks in its cyclic voltammograms for MG
      reduction. This occurred as two electron transfer process where MG gained two
      electrons from oxidized glutathione disulfide and formed hemithioacetal. The
      current density response of the fabricated bioelectrode was linear towards MG in
      the concentration range of 0.1-100 MUM with the correlation coefficient of 0.99,
      sensitivity of 1130.86 MUA cm-2 MUM-1, limit of detection of 2 nM and response
      time of less than 18 s. The developed bioelectrode was used for the detection of
      MG in raw and par-boiled rice samples.

PMID- 28445707
TI  - Comparing sprint and endurance training on anxiety, depression and its relation
      with brain-derived neurotrophic factor in rats.
AB  - Although the response of brain-derived neurotrophic factor (BDNF) has been shown
      to low intensity exercise training, but the effect of intensive exercise training
      is not clear. Also, there is insufficient information about relationship between
      BDNF and depression and anxiety following intensive exercise. This study aimed to
      investigate the effects of 6 weeks of intensive endurance training (ET) and
      sprint interval training (SIT) on brain BDNF and its relationship with anxiety
      and depression in Albino Wistar rats. Anxiety and depression of rats were
      measured by elevated plus maze (EPM) and tail suspension test (TST),
      respectively. All data were analyzed using one-way ANOVA and Pearson's
      correlation coefficient at P<0.05 level. Both SIT and ET regimens increased BDNF
      content in the brain, and the alterations made were greater following SIT than
      ET. Also, both SIT and ET regimens increased number of entries and the time spent
      in the open arm significantly in EPM, with a higher elevation following SIT than
      ET. In addition, both SIT and ET regimens decreased number and duration of
      immobility significantly in TST, with a higher reduction following SIT than ET.
      Furthermore, BDNF content correlated positively with number of entries and the
      time spent in the open arm in EPM and negatively with number and duration of
      immobility in TST. Collectively, sprint interval training regimen, rather than
      intensive endurance training regimen, is highly potential to improve anxiety and
      depression through a greater increase in BDNF contents in brain.

PMID- 28445708
TI  - Flow cytometry analysis of inflammatory cells isolated from the sciatic nerve and
      DRG after chronic constriction injury in mice.
AB  - BACKGROUND: Cellular responses to nerve injury play a central role in the
      pathogenesis of neuropathic pain. However, the analysis of site specific cellular
      responses to nerve injury and neuropathic pain is limited to immunohistochemistry
      staining with numerous limitations. NEW METHODS: We proposed to apply flow
      cytometry to overcome some of the limitations and developed two protocols for
      isolation of cells from small specimens of the sciatic nerve and dorsal root
      ganglion (DRG) in mice. RESULTS AND COMPARASION WITH EXISTING: methods We found
      that both the non-enzymatic and enzymatic approaches were highly effective in
      harvesting a sufficient number of cells for flow cytometry analysis in normal and
      pathological conditions. The total number of cells in the injury site of the
      sciatic and its DRGs increased significantly 14days after chronic constriction
      injury (CCI) of the sciatic nerve, compared to sham surgery control or the
      contralateral control. The enzymatic approach yielded a significantly higher
      total number of cells and CD45 negative cells, suggesting that this approach
      allows for harvest of more resident cells, compared to the non-enzymatic method.
      The percentage of CD45+/CD11b+ cells was significantly increased in the sciatic
      nerve but not in the DRG. These results were consistent with both protocols.
      CONCLUSIONS: We thus offer two simple and effective protocols that allow for
      application of flow cytometry to the investigation of cellular and molecular
      mechanisms of neuropathic pain.

PMID- 28445709
TI  - Gait analysis and weight bearing in pre-clinical joint pain research.
AB  - BACKGROUND: There is a need for better joint pain treatment, but development of
      new medication has not been successful. Pre-clinical models with readouts that
      better reflect the clinical situation are needed. In patients with joint pain,
      pain at rest and pain at walking are two major complaints. NEW METHOD: We
      describe a new way of calculating results from gait analysis using the CatWalkTM
      setup. Rats with monoarthritis induced by injection of Complete Freund's Adjuvant
      (CFA) intra-articularly into the ankle joint of one hind limb were used to assess
      gait and dynamic weight bearing. RESULTS: The results show that dynamic weight
      bearing was markedly reduced for the injected paw. Gait parameters such as amount
      of normal step sequences, walking speed and duration of step placement were also
      affected. Treatment with naproxen (an NSAID commonly used for inflammatory pain)
      attenuated the CFA-induced effects. Pregabalin, which is used for neuropathic
      pain, had no effect. COMPARISON WITH EXISTING METHODS: Reduced dynamic weight
      bearing during locomotion, assessed and calculated in the way we present here,
      showed a dose-dependent and lasting normalization after naproxen treatment. In
      contrast, static weight bearing while standing (Incapacitance tester) showed a
      significant effect for a limited time only. Mechanical sensitivity (von Frey
      Optihairs) was completely normalized by naproxen, and the window for testing
      pharmacological effect disappeared. CONCLUSIONS: Objective and reproducible
      effects, with an endpoint showing face validity compared to pain while walking in
      patients with joint pain, are achieved by a new way of calculating dynamic weight
      bearing in monoarthritic rats.

PMID- 28445710
TI  - Stereoselective preparation of quaternary 2-vinyl sphingosines and ceramides and
      their effect on basal sphingolipid metabolism.
AB  - The dicyclohexylborane-mediated addition of allene 1 to (E)-2-tridecenal affords
      a quaternary protected 2-amino-2-vinyl-1,3-diol in good yield as a single
      diastereomer. This compound is readily transformed into the four stereoisomers of
      the quaternary (E)-2-vinyl analogs of sphingosine. The metabolic fate and the
      effect of these compounds on the basal sphingolipid metabolism in human A549 lung
      adenocarcinoma cells has been studied, together with the ceramide analog of the
      most relevant vinylsphingosine derivative.

PMID- 28445711
TI  - The short-term behavioural response of sows, but not gilts, to a social stimulus
      is related to sow aggressiveness in groups.
AB  - This study examined relationships between the behavioural response of pregnant
      gilts (n=200, gestation 1) and sows (n=200, gestation 2) to a live, similarly
      aged female pig (unfamiliar pig test, UPT) and to a fibre-glass model pig (model
      pig test, MPT), and aggressive behaviour on the day after mixing (day 2). Sows
      with a short latency to make contact with an unfamiliar sow in the UPT were more
      likely to deliver high levels of aggression at day 2 of gestation 2 (P=0.005),
      but this relationship was stronger when a model pig was used (P<0.001).
      Similarly, sows with a long duration of tactile contact with the model pig in the
      MPT were more likely to deliver high levels of aggression at day 2 of gestation 2
      (P=0.015), but this relationship was weaker than that between aggression and the
      latency to contact the model pig. When the terms the latency to contact the
      unfamiliar pig in the UPT and the model pig in the MPT, as well as the duration
      of contact with the model pig in the MPT, were included in an overall model of
      aggression at day 2 of gestation 2, behaviour towards the unfamiliar pig became
      not statistically significant (P>0.05). A strong relationship was not apparent
      with gilts (P>0.05). Thus, the socially inexperienced pig may not be an ideal
      model for sow behaviour. This study indicates that sows with a short latency to
      contact a model pig are more likely to be aggressive when mixed into groups.

PMID- 28445712
TI  - Consider the context: Ras/ERK and PI3K/AKT/mTOR signaling outcomes are pituitary
      cell type-specific.
AB  - Conserved signaling pathways are critical regulators of pituitary homeostasis
      and, when dysregulated, contribute to adenoma formation. Pituitary adenomas are
      typically benign and rarely progress to malignant cancer. Pituitary and other
      neuroendocrine cell types often display non-proliferative responses to ERK and
      PI3K, in contrast to non-endocrine cell types which typically proliferate in
      response to ERK and PI3K activation. These differences likely contribute to the
      infrequent progression to malignancy in many endocrine tumors. In this review, we
      highlight the Ras/ERK and PI3K/AKT/mTOR signaling pathways in each pituitary cell
      type, as well as in other endocrine tissues. Furthermore, we provide evidence
      that a balance of ERK and PI3K signaling is required to maintain pituitary
      homeostasis. It is unlikely that one sole oncogene will be identified as being
      responsible for sporadic pituitary adenoma formation. This review emphasizes the
      necessity to consider endocrine cell-specific contexts and the interplay of
      signaling pathways to define the mechanisms underlying pituitary tumorigenesis.

PMID- 28445714
TI  - The toll-like receptor 2 agonist Pam3CSK4 is neuroprotective after spinal cord
      injury.
AB  - Microglia/macrophage activation and recruitment following spinal cord injury
      (SCI) is associated with both detrimental and reparative functions. Stimulation
      of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be
      beneficial following SCI, and it increases axonal regeneration following optic
      nerve crush. However, the mechanism(s) remain unclear. As microglia express high
      levels of TLR2, we hypothesized that modulating the microglial response to injury
      using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white
      matter degeneration following SCI. To test this hypothesis, we documented acute
      changes in microglia, axons, and oligodendroglia over time using two-photon
      excitation and an ex vivo laser-induced SCI (LiSCI) model. We utilized double
      transgenic mice that express GFP in either microglia or oligodendroglia, and YFP
      in axons, and we applied the lipophilic fluorescent dye (Nile Red) to visualize
      myelin. We found that treatment with Pam3CSK4 initiated one hour after injury
      induced a significant increase in the extent and timing of the microglial
      response to injury compared to vehicle controls. This enhanced response was
      observed 2 to 4h following SCI and was most prominent in areas closer to the
      ablation site. In addition, Pam3CSK4 treatment significantly reduced axonal
      dieback rostral and caudal to the ablation at 6h post-SCI. This protective effect
      of Pam3CSK4 was also mirrored when assessing secondary bystander axonal damage
      (i.e., axons spared by the primary injury that then succumb to secondary
      degeneration), and when assessing the survival of oligodendroglia. Following
      these imaging experiments, custom microarray analysis of the ex vivo spinal cord
      preparations revealed that Pam3CSK4-treatment induced an alternative (mixed
      M1:M2) microglial activation profile. In summary, our data suggest that by
      providing a second "sterile" activation signal to microglia through TLR2/TLR1
      signaling, the microglial response to injury can be modulated in situ and is
      highly neuroprotective.

PMID- 28445715
TI  - Altered somatosensory cortex neuronal activity in a rat model of Parkinson's
      disease and levodopa-induced dyskinesias.
AB  - Several findings support the concept that sensorimotor integration is disturbed
      in Parkinson's disease (PD) and in levodopa-induced dyskinesias. In this study,
      we explored the neuronal firing activity of excitatory pyramidal cells and
      inhibitory interneurons in the forelimb region of the primary somatosensory
      cortex (S1FL-Ctx), along with its interaction with oscillatory activity of the
      primary motor cortex (MCtx) in 6-hydroxydopamine lesioned hemiparkinsonian (HP)
      and levodopa-primed dyskinetic (HP-LID) rats as compared to controls under
      urethane (1.4g/kg, i.p.) anesthesia. Further, gene expression patterns of
      distinct markers for inhibitory GABAergic neurons were analyzed in both cortical
      regions. While firing frequency and burst activity of S1FL-Ctx inhibitory
      interneurons were reduced in HP and HP-LID rats, measures of irregularity were
      enhanced in pyramidal cells. Further, enhanced coherence of distinct frequency
      bands of the theta/alpha, high-beta, and gamma frequency, together with enhanced
      synchronization of putative pyramidal cells and interneurons with MCtx
      oscillatory activity were observed. While GABA level was similar, gene expression
      levels of interneuron and GABAergic markers in S1FL-Ctx and MCtx of HP-LID rats
      differed to some extent. Our study shows that in a rat model of PD with
      dyskinesias, neuronal activity in putative interneurons was reduced, which was
      accompanied by high beta and gamma coherence between S1FL-Ctx and MCtx, together
      with changes in gene expression, indicating maladaptive neuroplasticity after
      long term levodopa treatment.

PMID- 28445713
TI  - Deregulation of alpha-synuclein in Parkinson's disease: Insight from epigenetic
      structure and transcriptional regulation of SNCA.
AB  - Understanding regulation of alpha-synuclein has long been a central focus for
      Parkinson's disease (PD) researchers. Accumulation of this protein in the Lewy
      body or neurites, mutations in the coding region of the gene and strong
      association of alpha-synuclein encoding gene multiplication
      (duplication/triplication) with familial form of PD have indicated the importance
      of this molecule in pathogenesis of the disease. Several years of research
      identified many potential faulty pathways associated with accumulation of alpha
      synuclein inside dopaminergic neurons and its transmission to neighboring ones.
      Concurrently, an appreciable body of research is growing to understand the
      epigenetic and genetic deregulation of alpha-synuclein that might contribute to
      the disease pathology. Completion of the ENCODE (Encyclopedia of DNA Elements)
      project and recent advancement made in the epigenetic and trans factor mediated
      regulation of each gene, has tremendously accelerated the need to carefully
      understand the epigenetic structure of the gene (SNCA) encoding alpha-synuclein
      protein in order to decipher the regulation and contribution of alpha-synuclein
      to the pathogenesis of PD. We have also analyzed the detailed epigenetic
      structure of this gene with knowledge from ENCODE database, which may open new
      avenues in alpha-synuclein research. Interestingly, we have found that the gene
      contains several transcriptionally activate histone modifications and associated
      potential transcription factor binding sites in the non-coding areas that
      strongly suggest alternative regulatory pathways. Altogether this review will
      provide interesting insight of alpha-synuclein gene regulation from epigenetic,
      genetic and post-transcriptional perspectives and their potential implication in
      the PD pathogenesis.

PMID- 28445718
TI  - The HIV-1 Glycan Shield: Strategically Placed Kinks in the Armor Improve Antigen
      Design.
AB  - Dense glycosylation on the HIV-1 envelope glycoprotein hampers the induction of
      broadly neutralizing antibodies against HIV-1. Zhou et al. remove key glycans to
      unmask sites of vulnerability and enable the induction of neutralizing
      antibodies.

PMID- 28445717
TI  - Hepatic ELOVL6 mRNA is regulated by the gga-miR-22-3p in egg-laying hen.
AB  - The elongation of very long chain fatty acids protein 6 (ELOVL6) encodes a fatty
      acid elongase that is responsible for the final step in endogenous saturated
      fatty acid synthesis and involves in de novo lipogenesis. Though the regulatory
      mechanism of ELOVL6 expression has been studied extensively, little is known
      about the role of miRNA in regulating ELOVL6 gene expression in chicken until
      now. To investigate the regulatory mechanism of miRNA on the expression of ELOVL6
      gene, bioinformatics analysis was employed to predict the potential miRNAs that
      binding with the 3'untranslated region (3'UTR) of ELOVL6. The putative miRNA was
      further screened by comparative analysis with previous miRNA-seq results. Gga-miR
      22-3p, which could bind with the 3'UTR of ELOVL6 and showed negative expression
      correlation with ELOVL6 gene in chicken liver, was obtained. Tissue expression
      profiles showed that gga-miR-22-3p and ELOVL6 are extensively expressed in many
      tissues, and ELOVL6 with high expression level in kidney and liver tissues, and
      gga-miR-22-3p with high expression in lung and heart. Dual-luciferase reporter
      assays results indicated that the expression of luciferase reporter gene linked
      with part sequence of the 3'UTR of chicken ELOVL6 gene was down-regulated by the
      overexpression of gga-miR-22-3p in the DF1 cells, and the down-regulation
      behavior was abolished when the gga-miR-22-3p binding site in 3'UTR of ELOVL6 was
      mutated (P>0.05). Furthermore, the ELOVL6 expression in chicken hepatocytes was
      down-regulated when miR-22-3p was over-expressed. Therefore, we concluded that
      miR-22-3p might involve in controlling the hepatic lipid composition through
      affecting the expression of ELOVL6 gene, and could serve as a regulator of lipid
      metabolism in the liver of egg-laying hen.

PMID- 28445716
TI  - Trumping neurodegeneration: Targeting common pathways regulated by autosomal
      recessive Parkinson's disease genes.
AB  - Parkinson's disease (PD) is a neurodegenerative movement disorder characterized
      by the progressive loss of dopaminergic (DA) neurons. Most PD cases are sporadic;
      however, rare familial forms have been identified. Autosomal recessive PD (ARPD)
      results from mutations in Parkin, PINK1, DJ-1, and ATP13A2, while rare, atypical
      juvenile ARPD result from mutations in FBXO7, DNAJC6, SYNJ1, and PLA2G6. Studying
      these genes and their function has revealed mitochondrial quality control,
      protein degradation processes, and oxidative stress responses as common pathways
      underlying PD pathogenesis. Understanding how aberrancy in these common processes
      leads to neurodegeneration has provided the field with numerous targets that may
      be therapeutically relevant to the development of disease-modifying treatments.

PMID- 28445720
TI  - Hsp90 Is Essential under Heat Stress in the Bacterium Shewanella oneidensis.
AB  - The Hsp90 chaperone is essential in eukaryotes and activates a large array of
      client proteins. In contrast, its role is still elusive in bacteria, and only a
      few Hsp90 bacterial clients are known. Here, we found that Hsp90 is essential in
      the model bacterium Shewanella oneidensis under heat stress. A genetic screen for
      Hsp90 client proteins identified TilS, an essential protein involved in tRNA
      maturation. Overexpression of TilS rescued the growth defect of the hsp90
      deletion strain under heat stress. In vivo, the activity and the amount of TilS
      were significantly reduced in the absence of Hsp90 at high temperature.
      Furthermore, we showed that Hsp90 interacts with TilS, and Hsp90 prevents TilS
      aggregation in vitro at high temperature. Together, our results indicate that
      TilS is a client of Hsp90 in S. oneidensis. Therefore, our study links the
      essentiality of bacterial Hsp90 at high temperature with the identification of a
      client.

PMID- 28445719
TI  - KAT-Independent Gene Regulation by Tip60 Promotes ESC Self-Renewal but Not
      Pluripotency.
AB  - Although histone-modifying enzymes are generally assumed to function in a manner
      dependent on their enzymatic activities, this assumption remains untested for
      many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT),
      which is essential for embryonic stem cell (ESC) self-renewal and pre
      implantation development, performs these functions independently of its KAT
      activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal
      alterations in gene expression, chromatin accessibility at Tip60 binding sites,
      and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in
      ESC maintenance. In contrast, KAT-deficient ESCs exhibited impaired
      differentiation into mesoderm and endoderm, demonstrating a KAT-dependent
      function in differentiation. Consistent with this phenotype, KAT-deficient mouse
      embryos exhibited post-implantation developmental defects. These findings
      establish separable KAT-dependent and KAT-independent functions of Tip60 in ESCs
      and during differentiation, revealing a complex repertoire of regulatory
      functions for this essential chromatin remodeling complex.

PMID- 28445721
TI  - NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) participate in diverse
      aspects of brain function and mediate behavioral and addictive properties of
      nicotine. Neuronal nAChRs derive from combinations of alpha and beta subunits,
      whose assembly is tightly regulated. NACHO was recently identified as a chaperone
      for alpha7-type nAChRs. Here, we find NACHO mediates assembly of all major
      classes of presynaptic and postsynaptic nAChR tested. NACHO acts at early
      intracellular stages of nAChR subunit assembly and then synergizes with RIC-3 for
      receptor surface expression. NACHO knockout mice show profound deficits in
      binding sites for alpha-bungarotoxin, epibatidine, and conotoxin MII,
      illustrating essential roles for NACHO in proper assembly of alpha7-, alpha4beta2
      , and alpha6-containing nAChRs, respectively. By contrast, GABAA receptors are
      unaffected consistent with NACHO specifically modulating nAChRs. NACHO knockout
      mice show abnormalities in locomotor and cognitive behaviors compatible with
      nAChR deficiency and underscore the importance of this chaperone for physiology
      and disease associated with nAChRs.

PMID- 28445722
TI  - Genomic Analyses Reveal the Influence of Geographic Origin, Migration, and
      Hybridization on Modern Dog Breed Development.
AB  - There are nearly 400 modern domestic dog breeds with a unique histories and
      genetic profiles. To track the genetic signatures of breed development, we have
      assembled the most diverse dataset of dog breeds, reflecting their extensive
      phenotypic variation and heritage. Combining genetic distance, migration, and
      genome-wide haplotype sharing analyses, we uncover geographic patterns of
      development and independent origins of common traits. Our analyses reveal the
      hybrid history of breeds and elucidate the effects of immigration, revealing for
      the first time a suggestion of New World dog within some modern breeds. Finally,
      we used cladistics and haplotype sharing to show that some common traits have
      arisen more than once in the history of the dog. These analyses characterize the
      complexities of breed development, resolving longstanding questions regarding
      individual breed origination, the effect of migration on geographically distinct
      breeds, and, by inference, transfer of trait and disease alleles among dog
      breeds.

PMID- 28445723
TI  - Mosquitoes Transmit Unique West Nile Virus Populations during Each Feeding
      Episode.
AB  - Arthropod-borne viruses (arboviruses), such as Zika virus, chikungunya virus, and
      West Nile virus (WNV), pose continuous threats to emerge and cause large
      epidemics. Often, these events are associated with novel virus variants optimized
      for local transmission that first arise as minorities within a host. Thus, the
      conditions that regulate the frequency of intrahost variants are important
      determinants of emergence. Here, we describe the dynamics of WNV genetic
      diversity during its transmission cycle. By temporally sampling saliva from
      individual mosquitoes, we demonstrate that virus populations expectorated by
      mosquitoes are highly diverse and unique to each feeding episode. After
      transmission to birds, however, most genetic diversity is removed by strong
      purifying selection. Further, transmission of potentially mosquito-adaptive WNV
      variants is strongly influenced by genetic drift in mosquitoes. These results
      highlight the complex evolutionary forces a novel virus variant must overcome to
      alter infection phenotypes at the population level.

PMID- 28445724
TI  - Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.
AB  - While the HIV-1-glycan shield is known to shelter Env from the humoral immune
      response, its quantitative impact on antibody elicitation has been unclear. Here,
      we use targeted deglycosylation to measure the impact of the glycan shield on
      elicitation of antibodies against the CD4 supersite. We engineered diverse Env
      trimers with select glycans removed proximal to the CD4 supersite, characterized
      their structures and glycosylation, and immunized guinea pigs and rhesus
      macaques. Immunizations yielded little neutralization against wild-type viruses
      but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan
      deleted autologous viruses with over 90% breadth against four-glycan-deleted
      heterologous strains exhibiting tier 2 neutralization character). To a first
      approximation, the immunogenicity of the glycan-shielded protein surface was
      negligible, with Env-elicited neutralization (ID50) proportional to the
      exponential of the protein-surface area accessible to antibody. Based on these
      high titers and exponential relationship, we propose site-selective
      deglycosylated trimers as priming immunogens to increase the frequency of site
      targeting antibodies.

PMID- 28445726
TI  - Sirtuin-1 Activation Controls Tumor Growth by Impeding Th17 Differentiation via
      STAT3 Deacetylation.
AB  - Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of
      different cellular processes, particularly inflammation. Basal SIRT1 activity was
      previously found to limit Th9 and enhance Th17 differentiation in mice, but the
      effect of pharmacological SIRT1 activation on T cell differentiation and
      antitumor responses remains unclear. Here, we find that SIRT1 pharmacological
      agonists selectively impede mouse and human Th17 cell differentiation. SIRT1
      activation induces STAT3 deacetylation, thus reducing its ability to translocate
      into the nucleus, bind to Rorc promoter, and induce its transcription. SIRT1
      agonists reduce tumor growth in mice by blocking Th17 cell differentiation. In
      cancer patients, the SIRT1 agonist metformin reduced the frequency of Th17 cells
      and STAT3 acetylation levels. Altogether, these data underscore that SIRT1
      activation impedes Th17 cell differentiation and thereby limits tumor growth and
      suggest that SIRT1 activators may directly target IL-17A functions.

PMID- 28445725
TI  - NLRP6 Protects Il10-/- Mice from Colitis by Limiting Colonization of Akkermansia
      muciniphila.
AB  - Dysfunction in host immune responses and pathologic alterations in the gut
      microbiota, referred to as dysbiosis, can both contribute to the development of
      inflammatory bowel disease (IBD). However, it remains unclear how specific
      changes in host immunity or the microbiota cause disease. We previously
      demonstrated that the loss of the innate immune receptor NLRP6 in mice resulted
      in impaired production of interleukin-18 (IL-18) and increased susceptibility to
      epithelial-induced injury. Here, we show that NLRP6 is important for suppressing
      the development of spontaneous colitis in the Il10-/- mice model of IBD and that
      NLRP6 deficiency results in the enrichment of Akkermansia muciniphila. A.
      muciniphila was sufficient for promoting intestinal inflammation in both specific
      pathogen-free and germ-free Il10-/- mice. Our results demonstrate that A.
      muciniphila can act as a pathobiont to promote colitis in a genetically
      susceptible host and that NLRP6 is a key regulator of its abundance.

PMID- 28445727
TI  - Environmental Enrichment Induces Pericyte and IgA-Dependent Wound Repair and
      Lifespan Extension in a Colon Tumor Model.
AB  - Environmental enrichment (EE) replicates mind-body therapy by providing complex
      housing to laboratory animals to improve their activity levels, behavior, and
      social interactions. Using a Tcf4Het/+ApcMin/+-mediated model of colon
      tumorigenesis, we found that EE vastly improved the survival of tumor-bearing
      animals, with differential effect on tumor load in male compared to female
      animals. Analysis of Tcf4Het/+ApcMin/+ males showed drastically reduced
      expression of circulating inflammatory cytokines and induced nuclear hormone
      receptor (NHR) signaling, both of which are common in the wound repair process.
      Interestingly, EE provoked tumor wound repair resolution through
      revascularization, plasma cell recruitment and IgA secretion, replacement of
      glandular tumor structures with pericytes in a process reminiscent of scarring,
      and normalization of microbiota. These EE-dependent changes likely underlie the
      profound improvement in survival of colon-tumor-bearing Tcf4Het/+ApcMin/+ males.
      Our studies highlight the exciting promise of EE in the design of future
      therapeutic strategies for colon cancer patients.

PMID- 28445728
TI  - Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung
      Metastases.
AB  - Surgery remains the most successful curative treatment for cancer. However, some
      patients with early-stage disease who undergo surgery eventually succumb to
      distant metastasis. Here, we show that in response to surgery, the lungs become
      more vulnerable to metastasis due to extracellular matrix remodeling. Mice that
      undergo surgery or that are preconditioned with plasma from donor mice that
      underwent surgery succumb to lung metastases earlier than controls. Increased
      lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking,
      and focal adhesion signaling contribute to this effect, with the hypoxic surgical
      site serving as the source of LOX. Furthermore, the lungs of recipient mice
      injected with plasma from post-surgical colorectal cancer patients are more prone
      to metastatic seeding than mice injected with baseline plasma. Downregulation of
      LOX activity or levels reduces lung metastasis after surgery and increases
      survival, highlighting the potential of LOX inhibition in reducing the risk of
      metastasis following surgery.

PMID- 28445729
TI  - Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the
      Response to CD95L in Favor of NF-kappaB Activation and Cell Survival.
AB  - Formation of the death-inducing signaling complex (DISC) initiates extrinsic
      apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding
      to death-receptor-bound FADD. By elucidating the function of the caspase-8
      homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8
      mediated cell death. Significantly, we reveal that caspase-10 reduces DISC
      association and activation of caspase-8. Furthermore, we extend our co
      operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10
      does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout
      cells, we demonstrate that caspase-8 is required upstream of both cFLIP and
      caspase-10 and that DISC formation critically depends on the scaffold function of
      caspase-8. We establish that caspase-10 rewires DISC signaling to NF-kappaB
      activation/cell survival and demonstrate that the catalytic activity of caspase
      10, and caspase-8, is redundant in gene induction. Thus, our data are consistent
      with a model in which both caspase-10 and cFLIP coordinately regulate CD95L
      mediated signaling for death or survival.

PMID- 28445730
TI  - RIPK3 Mediates Necroptosis during Embryonic Development and Postnatal
      Inflammation in Fadd-Deficient Mice.
AB  - RIPK3 mediates cell death and regulates inflammatory responses. Although genetic
      studies have suggested that RIPK3-MLKL-mediated necroptosis leads to embryonic
      lethality in Fadd or Caspase-8-deficient mice, the exact mechanisms are not fully
      understood. Here, we generated Ripk3 mutant mice by altering the RIPK3 kinase
      domain (Ripk3Delta/Delta mice), thus abolishing its kinase activity.
      Ripk3Delta/Delta cells were resistant to necroptosis stimulation in vitro, and
      Ripk3Delta/Delta mice were protected from necroptotic diseases. Although the
      Ripk3Delta/Delta mutation rescued embryonic lethality in Fadd-/- embryos, Fadd-/
      Ripk3Delta/Delta mice died within 1 day after birth due to massive inflammation.
      These results indicate that Ripk3 ablation rescues embryonic lethality in Fadd
      deficient mice by suppressing two RIPK3-mediating processes: necroptosis during
      embryogenesis and inflammation during postnatal development in Fadd-/- mice.

PMID- 28445731
TI  - Hair Follicle Terminal Differentiation Is Orchestrated by Distinct Early and Late
      Matrix Progenitors.
AB  - During development and regeneration, matrix progenitors undergo terminal
      differentiation to form the concentric layers of the hair follicle. These
      differentiation events are thought to require signals from the mesenchymal dermal
      papilla (DP); however, it remains unclear how DP-progenitor cell interactions
      govern specific cell fate decisions. Here, we show that the hair follicle
      differentiated layers are specified asynchronously, with early matrix progenitors
      initiating differentiation before surrounding the DP. Furthermore, these early
      matrix cells can undergo terminal differentiation in the absence of Shh, BMP
      signaling, and DP maturation. Whereas early matrix progenitors form the hair
      follicle companion layer, later matrix populations progressively form the inner
      root sheath and hair shaft. Altogether, our findings characterize some of the
      earliest terminal differentiation events in the hair follicle and reveal that the
      matrix progenitor pool can be divided into early and late phases based on
      distinct temporal, molecular, and functional characteristics.

PMID- 28445732
TI  - The HECT Family Ubiquitin Ligase EEL-1 Regulates Neuronal Function and
      Development.
AB  - Genetic changes in the HECT ubiquitin ligase HUWE1 are associated with
      intellectual disability, but it remains unknown whether HUWE1 functions in post
      mitotic neurons to affect circuit function. Using genetics, pharmacology, and
      electrophysiology, we show that EEL-1, the HUWE1 ortholog in C. elegans,
      preferentially regulates GABAergic presynaptic transmission. Decreasing or
      increasing EEL-1 function alters GABAergic transmission and the
      excitatory/inhibitory (E/I) balance in the worm motor circuit, which leads to
      impaired locomotion and increased sensitivity to electroshock. Furthermore,
      multiple mutations associated with intellectual disability impair EEL-1 function.
      Although synaptic transmission defects did not result from abnormal synapse
      formation, sensitizing genetic backgrounds revealed that EEL-1 functions in the
      same pathway as the RING family ubiquitin ligase RPM-1 to regulate synapse
      formation and axon termination. These findings from a simple model circuit
      provide insight into the molecular mechanisms required to obtain E/I balance and
      could have implications for the link between HUWE1 and intellectual disability.

PMID- 28445733
TI  - NF-kappaB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age
      Related Neurodegeneration.
AB  - During aging, innate immunity progresses to a chronically active state. However,
      what distinguishes those that "age well" from those developing age-related
      neurological conditions is unclear. We used Drosophila to explore the cost of
      immunity in the aging brain. We show that mutations in intracellular negative
      regulators of the IMD/NF-kappaB pathway predisposed flies to toxic levels of
      antimicrobial peptides, resulting in early locomotor defects, extensive
      neurodegeneration, and reduced lifespan. These phenotypes were rescued when
      immunity was suppressed in glia. In healthy flies, suppressing immunity in glial
      cells resulted in increased adipokinetic hormonal signaling with high nutrient
      levels in later life and an extension of active lifespan. Thus, when levels of
      IMD/NF-kappaB deviate from normal, two mechanisms are at play: lower levels
      derepress an immune-endocrine axis, which mobilizes nutrients, leading to
      lifespan extension, whereas higher levels increase antimicrobial peptides,
      causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan
      determinant.

PMID- 28445734
TI  - Opposing Actions of Fgf8a on Notch Signaling Distinguish Two Muller Glial Cell
      Populations that Contribute to Retina Growth and Regeneration.
AB  - The teleost retina grows throughout life and exhibits a robust regenerative
      response following injury. Critical to both these events are Muller glia (or,
      Muller glial cells; MGs), which produce progenitors for retinal growth and
      repair. We report that Fgf8a may be an MG niche factor that acts through Notch
      signaling to regulate spontaneous and injury-dependent MG proliferation.
      Remarkably, forced Fgf8a expression inhibits Notch signaling and stimulates MG
      proliferation in young tissue but increases Notch signaling and suppresses MG
      proliferation in older tissue. Furthermore, cessation of Fgf8a signaling enhances
      MG proliferation in both young and old retinal tissue. Our study suggests that
      multiple MG populations contribute to retinal growth and regeneration, and it
      reveals a previously unappreciated role for Fgf8a and Notch signaling in
      regulating MG quiescence, activation, and proliferation.

PMID- 28445735
TI  - A Design Principle for an Autonomous Post-translational Pattern Formation.
AB  - Previous autonomous pattern-formation models often assumed complex molecular and
      cellular networks. This theoretical study, however, shows that a system composed
      of one substrate with multisite phosphorylation and a pair of kinase and
      phosphatase can generate autonomous spatial information, including complex stripe
      patterns. All (de-)phosphorylation reactions are described with a generic
      Michaelis-Menten scheme, and all species freely diffuse without pre-existing
      gradients. Computational simulation upon >23,000,000 randomly generated parameter
      sets revealed the design motifs of cyclic reaction and enzyme sequestration by
      slow-diffusing substrates. These motifs constitute short-range positive and long
      range negative feedback loops to induce Turing instability. The width and height
      of spatial patterns can be controlled independently by distinct reaction
      diffusion processes. Therefore, multisite reversible post-translational
      modification can be a ubiquitous source for various patterns without requiring
      other complex regulations such as autocatalytic regulation of enzymes and is
      applicable to molecular mechanisms for inducing subcellular localization of
      proteins driven by post-translational modifications.

PMID- 28445737
TI  - Rapid Automatic Motor Encoding of Competing Reach Options.

PMID- 28445738
TI  - Ochratoxin A and its metabolites in urines of German adults-An assessment of
      variables in biomarker analysis.
AB  - Ochratoxin A (OTA), a mycotoxin known for its nephrotoxic and carcinogenic
      properties, is a worldwide occurring contaminant in a variety of food
      commodities. Biomonitoring (i.e. analysis in biological fluids) can serve to
      assess human internal exposure from all consumed foods and beverages. We now
      determined the concentration of OTA and its metabolite ochratoxin alpha (OTalpha)
      in plasma and in urine of two male volunteers with different food habits, in
      order to assess intra-individual temporal fluctuations and inter-individual
      differences in their biomarker levels. Moreover, the urinary levels of both OTA
      and OTalpha were analyzed in a cohort of German adults (23 males, 27 females) on
      their regular diet. All samples were subjected to an enzymatic hydrolysis of
      biomarker conjugates prior to clean-up by liquid-liquid extraction and HPLC-FD
      analysis. The profile in the first individual showed small fluctuations over
      time: mean levels in plasma were 0.42 and 0.45ng/mL for OTA and OTalpha,
      respectively, and in urine means of 0.06ng/mL for both analytes. The other
      individual had mean levels of 1.64 and 0.20ng/mL for OTA and OTalpha in plasma,
      and 0.24 and 2.22ng/mL for these analytes in urine. It is concluded that inter
      individual differences in biomarker levels reflect dissimilar dietary exposure
      and/or disposition of ingested mycotoxin, with an apparently more efficient
      detoxification of OTA to OTalpha in the second individual. In the German cohort
      (n=50), analytes were detected in 100% (OTA: range 0.02-1.82ng/mL mean level
      0.21+/-0.31ng/mL) and 78% (OTalpha: range 0.01-14.25ng/mL, mean level 1.33+/
      2.63ng/mL) of all urines. Parameters such as gender, age and body mass index did
      not show a significant association with urine biomarker levels. This study
      indicates frequent exposure to OTA among German adults. The new results are
      discussed in the context of biomarker data from other countries and some
      methodological issues.

PMID- 28445736
TI  - Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma
      Progression.
AB  - The extent and nature of epigenomic changes associated with melanoma progression
      is poorly understood. Through systematic epigenomic profiling of 35 epigenetic
      modifications and transcriptomic analysis, we define chromatin state changes
      associated with melanomagenesis by using a cell phenotypic model of non
      tumorigenic and tumorigenic states. Computation of specific chromatin state
      transitions showed loss of histone acetylations and H3K4me2/3 on regulatory
      regions proximal to specific cancer-regulatory genes in important melanoma
      driving cell signaling pathways. Importantly, such acetylation changes were also
      observed between benign nevi and malignant melanoma human tissues. Intriguingly,
      only a small fraction of chromatin state transitions correlated with expected
      changes in gene expression patterns. Restoration of acetylation levels on
      deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked
      excessive proliferation in tumorigenic cells and human melanoma cells, suggesting
      functional roles of observed chromatin state transitions in driving
      hyperproliferative phenotype. Through these results, we define functionally
      relevant chromatin states associated with melanoma progression.

PMID- 28445739
TI  - Autophagy associated cytotoxicity and cellular uptake mechanisms of bismuth
      nanoparticles in human kidney cells.
AB  - Bismuth compounds have been used for treatment of bacterial infection, and
      recently bismuth nanoparticles (BiNP) were synthesized for imaging and diagnostic
      purpose, while safety concern of bismuth cannot be ignored. Here, we prepared
      ultrasmall BiNP and showed an enhanced tumor imaging, but BiNP revealed a
      differentiated cytotoxicity in human embryonic kidney 293 cells (HEK293) compared
      to other cell types. For the first time, we found that BiNP can induce autophagy,
      shown as the increase of monodansylcadaverine fluorescence staining and the
      amount of LC3II that can be inhibited by 3-MA. BiNP were capable of entering
      cells in a dose and time dependent manner by fluorescence and element detection
      methods BiNP were found to be localized in the cytoplasm observed by transmission
      electron microscopy and intracellular bismuth element confirmed by energy
      dispersive X-ray analysis. Using endocytic inhibitors, BiNP were found to require
      ATP and endosomal trafficking pathways for their cellular uptake. Internalized
      BiNP did not co-localize with EEA1, but co-localized with Lysotracker/LAMP1/LAMP2
      at late time points, indicating BiNP may be retained in the non-early endosomal
      vacuoles and late endosomes. With our novel finding of bismuth induced autophagy
      and endocytic mechanisms, potential approaches may be applied to reduce the
      toxicity by bismuth.

PMID- 28445740
TI  - Right brain, left brain in depressive disorders: Clinical and theoretical
      implications of behavioral, electrophysiological and neuroimaging findings.
AB  - The right and left side of the brain are asymmetric in anatomy and function. We
      review electrophysiological (EEG and event-related potential), behavioral
      (dichotic and visual perceptual asymmetry), and neuroimaging (PET, MRI, NIRS)
      evidence of right-left asymmetry in depressive disorders. Recent
      electrophysiological and fMRI studies of emotional processing have provided new
      evidence of altered laterality in depressive disorders. EEG alpha asymmetry and
      neuroimaging findings at rest and during cognitive or emotional tasks are
      consistent with reduced left prefrontal activity in depressed patients, which may
      impair downregulation of amygdala response to negative emotional information.
      Dichotic listening and visual hemifield findings for non-verbal or emotional
      processing have revealed abnormal perceptual asymmetry in depressive disorders,
      and electrophysiological findings have shown reduced right-lateralized
      responsivity to emotional stimuli in occipitotemporal or parietotemporal cortex.
      We discuss models of neural networks underlying these alterations. Of clinical
      relevance, individual differences among depressed patients on measures of right
      left brain function are related to diagnostic subtype of depression, comorbidity
      with anxiety disorders, and clinical response to antidepressants or cognitive
      behavioral therapy.

PMID- 28445741
TI  - Memory scrutinized through electrical brain stimulation: A review of 80 years of
      experiential phenomena.
AB  - Electrical brain stimulations (EBS) sometimes induce reminiscences, but it is
      largely unknown what type of memories they can trigger. We reviewed 80 years of
      literature on reminiscences induced by EBS and added our own database. We
      classified them according to modern conceptions of memory. We observed a
      surprisingly large variety of reminiscences covering all aspects of declarative
      memory. However, most were poorly detailed and only a few were episodic. This
      result does not support theories of a highly stable and detailed memory, as
      initially postulated, and still widely believed as true by the general public.
      Moreover, memory networks could only be activated by some of their nodes: 94.1%
      of EBS were temporal, although the parietal and frontal lobes, also involved in
      memory networks, were stimulated. The qualitative nature of memories largely
      depended on the site of stimulation: EBS to rhinal cortex mostly induced personal
      semantic reminiscences, while only hippocampal EBS induced episodic memories.
      This result supports the view that EBS can activate memory in predictable ways in
      humans.

PMID- 28445742
TI  - Beyond the "Bereitschaftspotential": Action preparation behind cognitive
      functions.
AB  - Research on preparatory brain processes taking place before acting shows
      unexpected connections with cognitive processing. From 50 years, we know that
      motor-related brain activity can be measured by electrocortical recordings 1-3s
      before voluntary actions. This readiness potential has been associated with
      increasing excitably of premotor and motor areas and directly linked to the
      kinematic of the upcoming action. Now we know that the mere motor preparation is
      only one function of a more complex preparatory activity. Recent research shows
      that before any action many cognitive processes may occur depending on various
      aspects of the action, such as complexity, meaning, emotional valence, fatigue
      and consequences of the action itself. In addition to studies on self-paced
      action, the review considers also studies on externally-triggered paradigms
      showing differences in preparation processes related to age, physical exercise,
      and task instructions. Evidences from electrophysiological and neuroimaging
      recording indicate that in addition to the motor areas, the prefrontal, parietal
      and sensory cortices may be active during action preparation to anticipate future
      events and calibrate responses.

PMID- 28445743
TI  - EGFR-targeted micelles containing near-infrared dye for enhanced photothermal
      therapy in colorectal cancer.
AB  - The purpose of this research was to investigate the effectiveness of epidermal
      growth factor receptor (EGFR) targeted micelles loaded with IR-780 (Cetuximab/IR
      780/micelles) for generating tumor targeting, multimodal images, and photothermal
      therapy (PTT). We initially studied the cellular uptake of these micelles using
      the HCT-116 and SW-620 cell lines. HCT-116 (high expression of EGFR) and SW-620
      (low expression of EGFR) cell lines were used to examine biodistribution and
      antitumor effects of Cetuximab/IR-780/micelles. Time-lapse near-IR fluorescence
      (NIRF) images also indicated the highest IR-780 accumulation from Cetuximab/IR
      780/micelles in HCT-116 tumors (p<0.05). HCT-116 tumors in tumor-bearing mice
      exhibited significantly higher accumulations of Cetuximab/IR-780/111In-micelles
      than SW-620 tumors in Micro-SPECT/CT imaging and biodistribution studies
      (p<0.05). Dual-radioisotope Nano-SPECT/CT imaging of Cetuximab/131I-IR-780/111In
      micelles demonstrated simultaneous high accumulation of both IR-780 and micelles
      in HCT-116 tumors, but not in SW-620 tumors. Regarding antitumor effects,
      following the Cetuximab/IR-780/micelles with PPT on day 6, all HCT-116 tumor
      bearing mice were cured. In contrast, SW-620 tumors relapsed at 13days after
      treatment. In summary, we expect that the Cetuximab/IR-780/micelles could enhance
      the antitumor effects by PTT in EGFR overexpression colorectal cancers through
      effective drug delivery nanoparticles.

PMID- 28445744
TI  - NMRbox: A Resource for Biomolecular NMR Computation.
AB  - Advances in computation have been enabling many recent advances in biomolecular
      applications of NMR. Due to the wide diversity of applications of NMR, the number
      and variety of software packages for processing and analyzing NMR data is quite
      large, with labs relying on dozens, if not hundreds of software packages.
      Discovery, acquisition, installation, and maintenance of all these packages is a
      burdensome task. Because the majority of software packages originate in academic
      labs, persistence of the software is compromised when developers graduate,
      funding ceases, or investigators turn to other projects. To simplify access to
      and use of biomolecular NMR software, foster persistence, and enhance
      reproducibility of computational workflows, we have developed NMRbox, a shared
      resource for NMR software and computation. NMRbox employs virtualization to
      provide a comprehensive software environment preconfigured with hundreds of
      software packages, available as a downloadable virtual machine or as a Platform
      as-a-Service supported by a dedicated compute cloud. Ongoing development includes
      a metadata harvester to regularize, annotate, and preserve workflows and
      facilitate and enhance data depositions to BioMagResBank, and tools for Bayesian
      inference to enhance the robustness and extensibility of computational analyses.
      In addition to facilitating use and preservation of the rich and dynamic software
      environment for biomolecular NMR, NMRbox fosters the development and deployment
      of a new class of metasoftware packages. NMRbox is freely available to not-for
      profit users.

PMID- 28445745
TI  - Increased Tissue Stiffness in Tumors from Mice with Neurofibromatosis-1 Optic
      Glioma.
AB  - Children with neurofibromatosis type 1 (NF1) cancer predisposition syndrome are
      prone to the development of low-grade brain tumors (gliomas) within the optic
      pathway (optic gliomas). One of the key obstacles to developing successful
      therapeutic strategies for these tumors is the striking lack of information about
      the mechanical properties that characterize these tumors relative to non
      neoplastic optic nerve tissue. To study the physical changes that may occur when
      an optic nerve glioma is present, we employed atomic force microscopy to measure
      the stiffness of healthy versus tumor-bearing optic nerve tissue. We found that
      the average elastic moduli of non-neoplastic and tumor-bearing optic nerves were
      ~3 and ~6 kPa, respectively. Based on previous studies implicating changes in
      extracellular matrix remodeling in other, related optic nerve pathological
      states, we found decreased expression of one major metalloproteinase protein (MMP
      2) and unchanged expression of lysyl oxidase and a second metalloproteinase, MMP
      9, in murine optic gliomas relative to normal non-neoplastic optic nerve.
      Collectively, these observations suggest a productive interplay between physical
      properties of mouse optic nerve gliomas and the extracellular matrix.

PMID- 28445746
TI  - Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional
      Regulatory Networks.
AB  - Network motifs, such as the feed-forward loop (FFL), introduce a range of complex
      behaviors to transcriptional regulatory networks, yet such properties are
      typically determined from their isolated study. We characterize the effects of
      crosstalk on FFL dynamics by modeling the cross regulation between two different
      FFLs and evaluate the extent to which these patterns occur in vivo. Analytical
      modeling suggests that crosstalk should overwhelmingly affect individual protein
      expression dynamics. Counter to this expectation we find that entire FFLs are
      more likely than expected to resist the effects of crosstalk (~20% for one
      crosstalk interaction) and remain dynamically modular. The likelihood that cross
      linked FFLs are dynamically correlated increases monotonically with additional
      crosstalk, but is independent of the specific regulation type or connectivity of
      the interactions. Just one additional regulatory interaction is sufficient to
      drive the FFL dynamics to a statistically different state. Despite the potential
      for modularity between sparsely connected network motifs, Escherichia coli (E.
      coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs
      remains modular. A gene ontology analysis reveals that stress response processes
      are significantly overrepresented in the cross-linked motifs found within E.
      coli. Although the daunting complexity of biological networks affects the
      dynamical properties of individual network motifs, some resist and remain
      modular, seemingly insulated from extrinsic perturbations-an intriguing
      possibility for nature to consistently and reliably provide certain network
      functionalities wherever the need arise.

PMID- 28445747
TI  - Physical and Functional Characterization of a Viral Genome Maturation Complex.
AB  - Genome packaging is strongly conserved in the complex double-stranded DNA
      viruses, including the herpesviruses and many bacteriophages. In these cases,
      viral DNA is packaged into a procapsid shell by a terminase enzyme. The packaging
      substrate is typically a concatemer composed of multiple genomes linked in a head
      to-tail fashion, and terminase enzymes perform two essential functions: 1)
      excision of a unit length genome from the concatemer (genome maturation) and 2)
      translocation of the duplex into a procapsid (genome packaging). While the
      packaging motors have been described in some detail, the maturation complexes
      remain ill characterized. Here we describe the assembly, physical
      characteristics, and catalytic activity of the lambda-genome maturation complex.
      The lambda-terminase protomer is composed of one large catalytic subunit tightly
      associated with two DNA recognition subunits. The isolated protomer binds DNA
      weakly and does not discriminate between nonspecific DNA and duplexes that
      contain the packaging initiation sequence, cos. The Escherichia coli integration
      host factor protein (IHF) is required for efficient lambda-development in vivo
      and a specific IHF recognition sequence is found within cos. We show that IHF and
      the terminase protomer cooperatively assemble at the cos site and that the small
      terminase subunit plays the dominant role in complex assembly. Analytical
      ultracentrifugation analysis reveals that the maturation complex is composed of
      four protomers and one IHF heterodimer bound at the cos site. Tetramer assembly
      activates the cos-cleavage nuclease activity of the enzyme, which matures the
      genome end in preparation for packaging. The stoichiometry and catalytic activity
      of the complex is reminiscent of the type IIE and IIF restriction endonucleases
      and the two systems may share mechanistic features. This study, to our knowledge,
      provides our first detailed glimpse into the structural and functional features
      of a viral genome maturation complex, an essential intermediate in the
      development of complex dsDNA viruses.

PMID- 28445748
TI  - Directional Force Originating from ATP Hydrolysis Drives the GroEL Conformational
      Change.
AB  - Protein functional mechanisms usually require conformational changes, and often
      there are known structures for the different conformational states. However,
      usually neither the origin of the driving force nor the underlying pathways for
      these conformational transitions is known. Exothermic chemical reactions may be
      an important source of forces that drive conformational changes. Here we
      investigate this type of force originating from ATP hydrolysis in the chaperonin
      GroEL, by applying forces originating from the chemical reaction. Specifically,
      we apply directed forces to drive the GroEL conformational changes and learn that
      there is a highly specific direction for applied forces to drive the closed form
      to the open form. For this purpose, we utilize coarse-grained elastic network
      models. Principal component analysis on 38 GroEL experimental structures yields
      the most important motions, and these are used in structural interpolation for
      the construction of a coarse-grained free energy landscape. In addition, we
      investigate a more random application of forces with a Monte Carlo method and
      demonstrate pathways for the closed-open conformational transition in both
      directions by computing trajectories that are shown upon the free energy
      landscape. Initial root mean square deviation (RMSD) between the open and closed
      forms of the subunit is 14.7 A and final forms from our simulations reach an
      average RMSD of 3.6 A from the target forms, closely matching the level of
      resolution of the coarse-grained model.

PMID- 28445749
TI  - Equilibrium Ensembles for Insulin Folding from Bias-Exchange Metadynamics.
AB  - Earliest events in the aggregation process, such as single molecule
      reconfiguration, are extremely important and the most difficult to characterize
      in experiments. To this end, we have used well-tempered bias exchange
      metadynamics simulations to determine the equilibrium ensembles of an insulin
      molecule under amyloidogenic conditions of low pH and high temperature. A bin
      based clustering method that uses statistics accumulated in bias exchange
      metadynamics trajectories was employed to construct a detailed thermodynamic and
      kinetic model of insulin folding. The highest lifetime, lowest free-energy
      ensemble identified consisted of native conformations adopted by a folded insulin
      monomer in solution, namely, the R-, the Rf-, and the T-states of insulin. The
      lowest free-energy structure had a root mean square deviation of only 0.15 nm
      from native x-ray structure. The second longest-lived metastable state was an
      unfolded, compact monomer with little similarity to the native structure. We have
      identified three additional long-lived, metastable states from the bin-based
      model. We then carried out an exhaustive structural characterization of
      metastable states on the basis of tertiary contact maps and per-residue
      accessible surface areas. We have also determined the lowest free-energy path
      between two longest-lived metastable states and confirm earlier findings of non
      two-state folding for insulin through a folding intermediate. The ensemble
      containing the monomeric intermediate retained 58% of native hydrophobic
      contacts, however, accompanied by a complete loss of native secondary structure.
      We have discussed the relative importance of nativelike versus nonnative tertiary
      contacts for the folding transition. We also provide a simple measure to
      determine the importance of an individual residue for folding transition.
      Finally, we have compared and contrasted this intermediate with experimental data
      obtained in spectroscopic, crystallographic, and calorimetric measurements during
      early stages of insulin aggregation. We have also determined stability of
      monomeric insulin by incubation at a very low concentration to isolate protein
      protein interaction effects.

PMID- 28445750
TI  - Effect of Phosphorylation on a Human-like Osteopontin Peptide.
AB  - The last decade established that the dynamic properties of the phosphoproteome
      are central to function and its modulation. The temporal dimension of
      phosphorylation effects remains nonetheless poorly understood, particularly for
      intrinsically disordered proteins. Osteopontin, selected for this study due to
      its key role in biomineralization, is expressed in many species and tissues to
      play a range of distinct roles. A notable property of highly phosphorylated
      isoforms of osteopontin is their ability to sequester nanoclusters of calcium
      phosphate to form a core-shell structure, in a fluid that is supersaturated but
      stable. In Biology, this process enables soft and hard tissues to coexist in the
      same organism with relative ease. Here, we extend our understanding of the effect
      of phosphorylation on a disordered protein, the recombinant human-like
      osteopontin rOPN. The solution structures of the phosphorylated and
      unphosphorylated rOPN were investigated by small-angle x-ray scattering and no
      significant changes were detected on the radius of gyration or maximum
      interatomic distance. The picosecond-to-nanosecond dynamics of the hydrated
      powders of the two rOPN forms were further compared by elastic and quasi-elastic
      incoherent neutron scattering. Phosphorylation was found to block some nanosecond
      side-chain motions while increasing the flexibility of other side chains on the
      faster timescale. Phosphorylation can thus selectively change the dynamic
      behavior of even a highly disordered protein such as osteopontin. Through such an
      effect on rOPN, phosphorylation can direct allosteric mechanisms, interactions
      with substrates, cofactors and, in this case, amorphous or crystalline
      biominerals.

PMID- 28445751
TI  - Curcumin Dictates Divergent Fates for the Central Salt Bridges in Amyloid-beta40
      and Amyloid-beta42.
AB  - There are three specific regions in the Amyloid beta (Abeta) peptide sequence
      where variations cause enhanced toxicity in Alzheimer's disease: the N-terminus,
      the central salt bridge, and the C-terminus. Here, we investigate if there is a
      close conformational connection between these three regions, which may suggest a
      concerted mechanism of toxicity. We measure the effects of Zn2+ and curcumin on
      Abeta40, and compare these with their previously reported effects on Abeta42.
      Abeta42 and Abeta40 differ only near the C-terminus, where curcumin interacts,
      while Zn2+ interacts near the N-terminus. Therefore, this comparison should help
      us differentiate the effect of modulating the C- and the N-termini. We find that
      curcumin allows fibril-like structures containing the salt bridge to emerge in
      the mature Abeta40 aggregates, but not in Abeta42. In contrast, we find no
      difference in the effects of Zn+2 on Abeta40 and Abeta42. In the presence of
      Zn+2, both of these fail to form proper fibrils, and the salt bridge remains
      disrupted. These results indicate that modulations of the Abeta termini can
      determine the fate of a salt bridge far away in the sequence, and this has
      significant consequences for Abeta toxicity. We also infer that small molecules
      can alter oligomer-induced toxicity by modulating the aggregation pathway,
      without substantially changing the final product of aggregation.

PMID- 28445752
TI  - Refolding of SDS-Unfolded Proteins by Nonionic Surfactants.
AB  - The strong and usually denaturing interaction between anionic surfactants (AS)
      and proteins/enzymes has both benefits and drawbacks: for example, it is put to
      good use in electrophoretic mass determinations but limits enzyme efficiency in
      detergent formulations. Therefore, studies of the interactions between proteins
      and AS as well as nonionic surfactants (NIS) are of both basic and applied
      relevance. The AS sodium dodecyl sulfate (SDS) denatures and unfolds globular
      proteins under most conditions. In contrast, NIS such as octaethylene glycol
      monododecyl ether (C12E8) and dodecyl maltoside (DDM) protect bovine serum
      albumin (BSA) from unfolding in SDS. Membrane proteins denatured in SDS can also
      be refolded by addition of NIS. Here, we investigate whether globular proteins
      unfolded by SDS can be refolded upon addition of C12E8 and DDM. Four proteins,
      BSA, alpha-lactalbumin (alphaLA), lysozyme, and beta-lactoglobulin (betaLG), were
      studied by small-angle x-ray scattering and both near- and far-UV circular
      dichroism. All proteins and their complexes with SDS were attempted to be
      refolded by the addition of C12E8, while DDM was additionally added to SDS
      denatured alphaLA and betaLG. Except for alphaLA, the proteins did not interact
      with NIS alone. For all proteins, the addition of NIS to the protein-SDS samples
      resulted in extraction of the SDS from the protein-SDS complexes and refolding of
      betaLG, BSA, and lysozyme, while alphaLA changed to its NIS-bound state instead
      of the native state. We conclude that NIS competes with globular proteins for
      association with SDS, making it possible to release and refold SDS-denatured
      proteins by adding sufficient amounts of NIS, unless the protein also interacts
      with NIS alone.

PMID- 28445753
TI  - Pyroglutamate-Modified Amyloid-beta(3-42) Shows alpha-Helical Intermediates
      before Amyloid Formation.
AB  - Pyroglutamate-modified amyloid-beta (pEAbeta) has been described as a relevant
      Abeta species in Alzheimer's-disease-affected brains, with pEAbeta (3-42) as a
      dominant isoform. Abeta (1-40) and Abeta (1-42) have been well characterized
      under various solution conditions, including aqueous solutions containing
      trifluoroethanol (TFE). To characterize structural properties of pEAbeta (3-42)
      possibly underlying its drastically increased aggregation propensity compared to
      Abeta (1-42), we started our studies in various TFE-water mixtures and found
      striking differences between the two Abeta species. Soluble pEAbeta (3-42) has an
      increased tendency to form beta-sheet-rich structures compared to Abeta (1-42),
      as indicated by circular dichroism spectroscopy data. Kinetic assays monitored by
      thioflavin-T show drastically accelerated aggregation leading to large fibrils
      visualized by electron microscopy of pEAbeta (3-42) in contrast to Abeta (1-42).
      NMR spectroscopy was performed for backbone and side-chain chemical-shift
      assignments of monomeric pEAbeta (3-42) in 40% TFE solution. Although the
      difference between pEAbeta (3-42) and Abeta (1-42) is purely N-terminal, it has a
      significant impact on the chemical environment of >20% of the total amino acid
      residues, as revealed by their NMR chemical-shift differences. Freshly dissolved
      pEAbeta (3-42) contains two alpha-helical regions connected by a flexible linker,
      whereas the N-terminus remains unstructured. We found that these alpha-helices
      act as a transient intermediate to beta-sheet and fibril formation of pEAbeta (3
      42).

PMID- 28445754
TI  - Probing the Dynamics of Clot-Bound Thrombin at Venous Shear Rates.
AB  - In closed system models of fibrin formation, exosite-mediated thrombin binding to
      fibrin contributes to clot stability and is resistant to inhibition by
      antithrombin/heparin while still susceptible to small, active-site inhibitors.
      Each molecule of fibrin can bind ~1.6 thrombin molecules at low-affinity binding
      sites (Kd = 2.8 MUM) and ~0.3 molecules of thrombin at high-affinity binding
      sites (Kd = 0.15 MUM). The goal of this study is to assess the stability of
      fibrin-bound thrombin under venous flow conditions and to determine both its
      accessibility and susceptibility to inhibition. A parallel-plate flow chamber (7
      * 50 * 0.25 mm) for studying the stability of thrombin (0-1400 nM) adhered to a
      fibrin matrix (0.1-0.4 mg/mL fibrinogen, 10 nM thrombin) under a variety of
      venous flow conditions was developed using the thrombin-specific, fluorogenic
      substrate SN-59 (100 MUM). The flow within this system is laminar (Re < 1) and
      reaction rates are driven by enzyme kinetics (Pe = 100, Da = 7000). A
      subpopulation of active thrombin remains stably adhered to a fibrin matrix over a
      range of venous shear rates (46-184 s-1) for upwards of 30 min, and this
      population is saturable at loads >500 nM and sensitive to the initial fibrinogen
      concentration. These observations were also supported by a mathematical model of
      thrombin adhesion to fibrin, which demonstrates that thrombin initially binds to
      the low-affinity thrombin binding sites before preferentially equilibrating to
      higher affinity sites. Antithrombin (2.6 MUM) plus heparin (4 U/mL) inhibits 72%
      of the active clot-bound thrombin after ~10 min at 92 s-1, while no inhibition is
      observed in the absence of heparin. Dabigatran (20 and 200 nM) inhibits (50 and
      93%) clot-bound thrombin reversibly (87 and 66% recovery). This model illustrates
      that clot-bound thrombin stability is the result of a constant rearrangement of
      thrombin molecules within a dense matrix of binding sites.

PMID- 28445755
TI  - Mapping Ryanodine Binding Sites in the Pore Cavity of Ryanodine Receptors.
AB  - Ryanodine (Ryd) irreversibly targets ryanodine receptors (RyRs), a family of
      intracellular calcium release channels essential for many cellular processes
      ranging from muscle contraction to learning and memory. Little is known of the
      atomistic details about how Ryd binds to RyRs. In this study, we used all-atom
      molecular dynamics simulations with both enhanced and bidirectional sampling to
      gain direct insights into how Ryd interacts with major residues in RyRs that were
      experimentally determined to be critical for its binding. We found that the
      pyrrolic ring of Ryd displays preference for the R4892AGGG-F4921 residues in the
      cavity of RyR1, which explain the effects of the corresponding mutations in RyR2
      in experiments. Particularly, the mutant Q4933A (or Q4863A in RyR2) critical for
      both the gating and Ryd binding not only has significantly less interaction with
      Ryd than the wild-type, but also yields more space for Ryd and water molecules in
      the cavity. These results describe clear binding modes of Ryd in the RyR cavity
      and offer structural mechanisms explaining functional data collected on RyR
      blockade.

PMID- 28445756
TI  - Membrane Mechanics of Primary Afferent Neurons in the Dorsal Root Ganglia of
      Rats.
AB  - Membrane mechanics is an important biological factor regulating many cellular
      functions including cell motility, intercellular and intracellular signaling,
      gene expression, and membrane ion channel activity. Primary afferent neurons
      transduce sensory information about temperature, touch, and pain. These sensory
      functions may be profoundly affected by the states of primary afferent neuron
      mechanics. However, membrane mechanics of primary afferent neurons is largely
      unknown. In this study, we established the optical trapping technique for
      determining membrane mechanics of cultured primary afferent neurons of the dorsal
      root ganglia (DRG). We further determined the roles of cytoskeleton and membrane
      lipids in DRG neuron mechanics. We found that DRG neurons had a plasma membrane
      tension of ~54 pN/MUm, and the tension was significantly decreased to ~29 pN/MUm
      by cytochalasin D treatment to disrupt actin cytoskeleton and increased to ~79
      pN/MUm by methyl-beta-cyclodextrin treatment to sequester membrane cholesterol.
      DRG neuron membrane stiffness was not significantly affected by the cytoskeleton
      disruption but was significantly increased after cholesterol sequestration. Our
      findings elucidate membrane mechanical properties of primary afferent neurons,
      which provide, to our knowledge, a new perspective on their sensory functions.

PMID- 28445757
TI  - Action of Antimicrobial Peptides on Bacterial and Lipid Membranes: A Direct
      Comparison.
AB  - The bacterial membrane represents an attractive target for the design of new
      antibiotics to combat widespread bacterial resistance. Understanding how
      antimicrobial peptides (AMPs) and other membrane-active agents attack membranes
      could facilitate the design of new, effective antimicrobials. Despite intense
      study of AMPs on model membranes, we do not know how well the mechanism of attack
      translates to real biological membranes. To that end, we have characterized the
      attack of AMPs on Escherichia coli cytoplasmic membranes and directly compared
      this action to model membranes. AMPs induce membrane permeability in E. coli
      spheroplasts or giant unilamellar vesicles (GUVs) under well-defined
      concentrations of AMPs and fluorescent molecules. The action of AMPs on
      spheroplasts is unique in producing an intracellular fluorescence intensity time
      curve that increases in a sigmoidal fashion to a steady state. This regular
      pattern is reproducible by melittin, LL37, and alamethicin but not by CCCP or
      daptomycin, agents known to cause ion leakage. Remarkably, a similar pattern was
      also reproduced in GUVs. Indeed the steady-state membrane permeability induced by
      AMPs is quantitatively the same in spheroplasts and GUVs. There are, however,
      interesting dissimilarities in details that reveal differences between bacterial
      and lipid membranes. Spheroplast membranes are permeabilized by a wide range of
      AMP concentrations to the same steady-state membrane permeability. In contrast,
      only a narrow range of AMP concentrations permeabilized GUVs to a steady state.
      Tension in GUVs also influences the action of AMPs, whereas the spheroplast
      membranes are tensionless. Despite these differences, our results provide a
      strong support for using model membranes to study the molecular interactions of
      AMPs with bacterial membranes. As far as we know, this is the first time the
      actions of AMPs, on bacterial membranes and on model membranes, have been
      directly and quantitatively compared.

PMID- 28445758
TI  - Bilayer Interactions among Unsaturated Phospholipids, Sterols, and Ceramide.
AB  - Using differential scanning calorimetry and lifetime analysis of trans-parinaric
      acid fluorescence, we have examined how cholesterol and cholesteryl
      phosphocholine (CholPC) affect gel-phase properties of palmitoyl ceramide (PCer)
      in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dioleyol-sn
      glycero-3-phosphocholine (DOPC) bilayers. By 2H NMR, we also measured fluid-phase
      interactions among these lipids using deuterated analogs of POPC, PCer, and
      cholesterol. The PCer-rich gel phase in POPC bilayers (9:1 molar ratio of POPC to
      PCer) was partially and similarly dissolved (and thermostability decreased) by
      both cholesterol and CholPC (sterol was present equimolar to PCer, or in fourfold
      excess). In DOPC bilayers (4:1 DOPC/PCer molar ratio), CholPC was much more
      efficient in dissolving the PCer-rich gel phase when compared to cholesterol.
      This can be interpreted as indicating that PCer interaction with POPC was
      stronger than PCer interaction with DOPC. PCer-CholPC interactions were also more
      favored in DOPC bilayers compared to POPC bilayers. In the fluid POPC-rich phase,
      cholesterol increased the order of the acyl chain of d2-PCer much more than did
      CholPC. In DOPC-rich fluid bilayers, both cholesterol and CholPC increased d2
      PCer acyl chain order, and the ordering induced by CholPC was more efficient in
      DOPC than in POPC bilayers. In fluid POPC bilayers, the ordering of 3-d1
      cholesterol by PCer was weak. In summary, we found that in the gel phase, sterol
      effects on the PCer-rich gel phase were markedly influenced by the acyl chain
      composition of the fluid PC. The same was true for fluid-phase interactions
      involving the sterols. Our results further suggest that PCer did not display high
      affinity toward either of the sterols used. We conclude that the nature of
      unsaturated phospholipids (POPC versus DOPC) in bilayers has major effects on the
      properties of ceramide gel phases and on sterol-ceramide-phospholipid
      interactions in such complex bilayers.

PMID- 28445759
TI  - Pulsatile Lipid Vesicles under Osmotic Stress.
AB  - The response of lipid bilayers to osmotic stress is an important part of cellular
      function. Recent experimental studies showed that when cell-sized giant
      unilamellar vesicles (GUVs) are exposed to hypotonic media, they respond to the
      osmotic assault by undergoing a cyclical sequence of swelling and bursting
      events, coupled to the membrane's compositional degrees of freedom. Here, we
      establish a fundamental and quantitative understanding of the essential pulsatile
      behavior of GUVs under hypotonic conditions by advancing a comprehensive
      theoretical model of vesicle dynamics. The model quantitatively captures the
      experimentally measured swell-burst parameters for single-component GUVs, and
      reveals that thermal fluctuations enable rate-dependent pore nucleation, driving
      the dynamics of the swell-burst cycles. We further extract constitutional scaling
      relationships between the pulsatile dynamics and GUV properties over multiple
      timescales. Our findings provide a fundamental framework that has the potential
      to guide future investigations on the nonequilibrium dynamics of vesicles under
      osmotic stress.

PMID- 28445760
TI  - Determining the Spatial Relationship of Membrane-Bound Aquaporin-4 Autoantibodies
      by STED Nanoscopy.
AB  - Determining the spatial relationship of individual proteins in dense assemblies
      remains a challenge for superresolution nanoscopy. The organization of aquaporin
      4 (AQP4) into large plasma membrane assemblies provides an opportunity to image
      membrane-bound AQP4 antibodies (AQP4-IgG) and evaluate changes in their spatial
      distribution due to alterations in AQP4 isoform expression and AQP4-IgG epitope
      specificity. Using stimulated emission depletion nanoscopy, we imaged secondary
      antibody labeling of monoclonal AQP4-IgGs with differing epitope specificity
      bound to isolated tetramers (M1-AQP4) and large orthogonal arrays of AQP4 (M23
      AQP4). Imaging secondary antibodies bound to M1-AQP4 allowed us to infer the size
      of individual AQP4-IgG binding events. This information was used to model the
      assembly of larger AQP4-IgG complexes on M23-AQP4 arrays. A scoring algorithm was
      generated from these models to characterize the spatial arrangement of bound AQP4
      IgG antibodies, yielding multiple epitope-specific patterns of bound antibodies
      on M23-AQP4 arrays. Our results delineate an approach to infer spatial
      relationships within protein arrays using stimulated emission depletion
      nanoscopy, offering insight into how information on single antibody fluorescence
      events can be used to extract information from dense protein assemblies under a
      biologic context.

PMID- 28445761
TI  - Live-Cell Super-resolution Reveals F-Actin and Plasma Membrane Dynamics at the T
      Cell Synapse.
AB  - The cortical actin cytoskeleton has been shown to be critical for the
      reorganization and heterogeneity of plasma membrane components of many cells,
      including T cells. Building on previous studies at the T cell immunological
      synapse, we quantitatively assess the structure and dynamics of this meshwork
      using live-cell superresolution fluorescence microscopy and spatio-temporal image
      correlation spectroscopy. We show for the first time, to our knowledge, that not
      only does the dense actin cortex flow in a retrograde fashion toward the synapse
      center, but the plasma membrane itself shows similar behavior. Furthermore, using
      two-color, live-cell superresolution cross-correlation spectroscopy, we
      demonstrate that the two flows are correlated and, in addition, we show that
      coupling may extend to the outer leaflet of the plasma membrane by examining the
      flow of GPI-anchored proteins. Finally, we demonstrate that the actin flow is
      correlated with a third component, alpha-actinin, which upon CRISPR knockout led
      to reduced plasma membrane flow directionality despite increased actin flow
      velocity. We hypothesize that this apparent cytoskeletal-membrane coupling could
      provide a mechanism for driving the observed retrograde flow of signaling
      molecules such as the TCR, Lck, ZAP70, LAT, and SLP76.

PMID- 28445762
TI  - Analysis of Active Transport by Fluorescence Recovery after Photobleaching.
AB  - Fluorescence recovery after photobleaching (FRAP) is a well-established
      experimental technique to study binding and diffusion of molecules in cells.
      Although a large number of analytical and numerical models have been developed to
      extract binding and diffusion rates from FRAP recovery curves, active transport
      of molecules is typically not included in the existing models that are used to
      estimate these rates. Here we present a validated numerical method for estimating
      diffusion, binding/unbinding rates, and active transport velocities using FRAP
      data that captures intracellular dynamics through partial differential equation
      models. We apply these methods to transport and localization of mRNA molecules in
      Xenopus laevis oocytes, where active transport processes are essential to
      generate developmental polarity. By providing estimates of the effective
      velocities and diffusion, as well as expected run times and lengths, this
      approach can help quantify dynamical properties of localizing and nonlocalizing
      RNA. Our results confirm the distinct transport dynamics in different regions of
      the cytoplasm, and suggest that RNA movement in both the animal and vegetal
      directions may influence the timescale of RNA localization in Xenopus oocytes. We
      also show that model initial conditions extracted from FRAP postbleach
      intensities prevent underestimation of diffusion, which can arise from the
      instantaneous bleaching assumption. The numerical and modeling approach presented
      here to estimate parameters using FRAP recovery data is a broadly applicable tool
      for systems where intracellular transport is a key molecular mechanism.

PMID- 28445764
TI  - Development of light-driven gas-forming liposomes for efficient tumor treatment.
AB  - In this study, we report a gas-forming liposome containing 1H-1H-2H-perfluoro-1
      hexene (PFH) and gold nanoparticles (AuNPs). These liposomes were rapidly
      destabilized by external near-infrared (NIR) light, as a result of the
      vaporization of PFH influenced by an AuNPs-mediated photothermal event. In
      particular, these liposomes showed the triggered release of the encapsulated d
      (KLAKLAK)2 peptide drug. The experimental results demonstrated that the light
      irradiated liposomes significantly enhanced in vitro photothermal and d
      (KLAKLAK)2 peptide-mediated cell death of CAOV-3 tumor cells.

PMID- 28445763
TI  - Myosin Rod Hypophosphorylation and CB Kinetics in Papillary Muscles from a TnC
      A8V KI Mouse Model.
AB  - The cardiac troponin C (TnC)-A8V mutation is associated with hypertrophic and
      restrictive cardiomyopathy (HCM and RCM) in human and mice. The residue affected
      lies in the N-helix, a region known to affect Ca2+-binding affinity to the N
      terminal domain. Here we report on the functional effects of this mutation in
      skinned papillary muscle fibers from homozygous knock-in TnC-A8V mice. Muscle
      fibers from left ventricle were activated at 25 degrees C under the ionic
      conditions of working cardiomyocytes. The pCa-tension relationship showed a 3*
      increase in Ca2+-sensitivity and a decrease (0.8*) in cooperativity (nH) in
      mutant fibers. The elementary steps of the cross-bridge (CB) cycle were
      investigated by sinusoidal analysis. The ATP study revealed that there is no
      significant change in the affinity of ATP (K1) for the myosin head. In TnC-A8V
      mutant fibers, the CB detachment rate (k2) and its equilibrium constant (K2)
      increased (1.5*). The phosphate study revealed that rate constant of the force
      generation step (k4) decreased (0.5*), reversal step (k-4) increased (2*), and
      the phosphate-release step (1/K5) increased (2*). Pro-Q Diamond staining of the
      skinned fibers samples revealed no significant changes in total phosphorylation
      of multiple sarcomeric proteins. Further investigation using liquid
      chromatography-tandem mass spectrometry revealed hypophosphorylation of the rod
      domain of myosin heavy chain in TnC-A8V mutant fibers compared to wild-type.
      Immunoblotting confirmed the results observed in the mass spectrometry analysis.
      The results suggest perturbed CB kinetics-possibly caused by changes in the alpha
      myosin heavy chain phosphorylation profile-as a novel mechanism, to our
      knowledge, by which a mutation in TnC can have rippling effects in the
      myofilament and contribute to the pathogenesis of HCM/RCM.

PMID- 28445765
TI  - In-line monitoring and optimization of powder flow in a simulated continuous
      process using transmission near infrared spectroscopy.
AB  - In-line monitoring of continuous powder flow is an integral part of the
      continuous manufacturing process of solid oral dosage forms in the pharmaceutical
      industry. Specifically, monitoring downstream from loss-in-weight (LIW) feeders
      and/or continuous mixers provides important data about the state of the process.
      Such measurements support control of the process and thereby enhance product
      quality. Near Infrared Spectroscopy (NIRS) is a potential PAT tool to monitor the
      homogeneity of a continuous powder flow stream in pharmaceutical manufacturing.
      However, the association of analytical results from NIR sampling of the powder
      stream and the homogeneity (content uniformity) of the resulting tablets provides
      several challenges; appropriate sampling strategies, adequately robust modeling
      techniques and poor sensitivities (for low dose APIs) are amongst them.
      Information from reflectance-based NIRS sampling is limited. The region of the
      powder bed that is interrogated is confined to the surface where the measurement
      is made. This potential bias in sampling may, in turn, limit the ability to
      predict the homogeneity of the finished dosage form. Further, changes to the
      processing parameters (e.g., rate of powder flow) often have a significant effect
      on the resulting data. Sample representation, interdependence between process
      parameters and their effects on powder flow behavior are critical factors for
      NIRS monitoring of continuous powder flow system. A transmission NIR method was
      developed as an alternative technique to monitor continuous powder flow and
      quantify API in the powder stream. Transmission NIRS was used to determine the
      thickness of the powder stream flowing from a loss-in-weight feeder. The
      thickness measurement of the powder stream provided an in-depth understanding
      about the effects of process parameters such as tube angles and powder flow rates
      on powder flow behaviors. This knowledge based approach helped to define an
      analytical design space that was specific to flow properties and to determine the
      optimum process parameters for successful quantitation of powder stream. A PAT
      method based on transmission NIRS was developed to monitor the homogeneity of API
      in a continuously flowing powder stream.

PMID- 28445766
TI  - Inhibitory effect of emulsifiers in sedds on protease activity: Just an illusion?
AB  - AIM: Evaluation of inhibitory effect of emulsifiers on pancreatic trypsin and
      alpha-chymotrypsin. METHODS: The inhibitory effect of Cremophor EL, Cremophor RH
      40, Brij O10, Tween 20, polyethylene glycol 8000, polyethylene glycol 400,
      Carbitol, Pemulen TR-1, Pemulen TR-2, Carbopol Ultrez 20 and Carbopol Ultrez 21
      on pancreatic trypsin and alpha-chymotrypsin was tested. BAEE (Nalpha-Benzoyl-l
      arginine ethyl ester), BTEE (N-Benzoyl-l-tyrosine ethyl ester), casein and
      insulin were used as substrates for trypsin and alpha-chymotrypsin. SEDDS
      containing Pemulen TR-2 were developed, loaded with insulin-DMPG
      (dimyristoylphosphatidylglycerol) complex, characterized and tested regarding the
      protective effect towards the proteolytic degradation of insulin. RESULTS:
      Cremophor EL, Cremophor RH 40, Brij O10, Tween 20, polyethylene glycol 8000,
      polyethylene glycol 400, Carbitol did not show any inhibitory effect towards
      trypsin and alpha-chymotrypsin, whereas Pemulen TR-1, Pemulen TR-2, Carbopol
      Ultrez 20 and Carbopol Ultrez 21 inhibited the enzymes in a concentration
      dependent manner. Moreover, Pemulen and Carbopol Ultrez emulsifiers exhibited
      comparable inhibitory properties (p>0.05). The incorporation of 0.34% w/w of
      Pemulen TR-2 in SEDDS decreased the degradation rate of the loaded insulin-DMPG
      complex compared to the blank formulation (p<0.05). CONCLUSION: The present study
      revealed that commonly used emulsifiers in SEDDS do not have inhibitory
      properties on the proteolytic activity of trypsin and alpha-chymotrypsin.
      Moreover, it was demonstrated that the incorporation of emulsifiers with
      inhibitory properties towards trypsin and alpha-chymotrypsin in SEDDS play a
      minor role in the protection of embedded drugs from enzymatic degradation.

PMID- 28445767
TI  - The 'Visualized' macrocycles: Chemistry and application of fluorophore tagged
      cyclodextrins.
AB  - Cyclodextrins are macrocyclic molecules able to form host-guest complexes due to
      their hydrophobic cavity. Because of their carbohydrate nature they do not absorb
      light in the UV-vis region (200-800nm), but they can be converted into
      spectroscopically active compounds via modification with a chromophore unit.
      Among the chromophores, the group of fluorophores can provide high sensitivity in
      analytical applications (chemosensing) and low detection limit in optical imaging
      methods (fluorescent microscopy). Fluorophore-tagged cyclodextrins therefore
      combine interesting spectroscopic properties with promising supramolecular
      features which make these conjugates widely applicable in various pharmaceutical
      fields. The aim of this work is to review the various types of fluorophores which
      have been used for cyclodextrin tagging, to discuss the synthetic strategies used
      for the conjugation and to summarize the pharmaceutical applications of these
      'visualized' macrocycles including their use in photodynamic therapy. The recent
      achievements in studying how the fluorophore-appended cyclodextrin derivatives
      cross biological barriers are also reviewed.

PMID- 28445768
TI  - Polymer-free electrospun nanofibers from sulfobutyl ether7-beta-cyclodextrin
      (SBE7-beta-CD) inclusion complex with sulfisoxazole: Fast-dissolving and enhanced
      water-solubility of sulfisoxazole.
AB  - In this study, our aim was to develop solid drug-cyclodextrin inclusion complex
      system having nanofibrous morphology in order to have fast-dissolving property
      and enhanced water-solubility of poorly water-soluble drug. Here, we prepared a
      highly concentrated aqueous solution of inclusion complex between sulfisoxazole
      and sulfobutyl ether7-beta-cyclodextrin (SBE7-beta-CD, Captisol(r)), and then,
      without using any polymeric matrix, the electrospinning of sulfisoxazole/SBE7
      beta-CD-IC nanofibers was performed in order to obtain free-standing and handy
      nanofibrous web. As a control sample, nanofibers from pure SBE7-beta-CD was also
      electrospun and free-standing nanofibrous web was obtained. The SEM imaging
      revealed that the bead-free and uniform nanofiber morphology with the average
      fiber diameter (AFD) of 650+/-290nm for sulfisoxazole/SBE7-beta-CD-IC NF and
      890+/-415nm for pure SBE7-beta-CD NF was obtained. The inclusion complex
      formation between sulfisoxazole and SBE7-beta-CD in sulfisoxazole/SBE7-beta-CD-IC
      NF sample was confirmed by 1H NMR, TGA, DSC, XRD and FTIR analyses. Due to the
      combined advantage of cyclodextrin inclusion complexation and high surface area
      of electrospun nanofibers, fast-dissolving property with enhanced water
      solubility was successfully achieved for sulfisoxazole/SBE7-beta-CD-IC NF. Our
      findings suggest that electrospun nanofibers/nanowebs from CD-IC of poorly water
      soluble drugs may offer applicable approaches for high water-solubility and fast
      dissolving tablet formulations for drug delivery systems.

PMID- 28445769
TI  - Evidence for mast cell-mediated zinc homeostasis: Increased labile zinc in the
      hippocampus of mast-cell deficient mice.
AB  - The dentate gyrus of the hippocampus is a site of adult neurogenesis, and is also
      known to contain one of the highest concentrations of labile brain zinc (Zn),
      thought to aid in learning and memory by supporting neurogenesis. At the same
      time, it is known that unbound Zn, when present at excessive levels, decreases
      the formation of new neurons. Since mast cells contain Zn transporters capable of
      moving this essential element across their plasma membrane, as well as Zn-rich
      granules that are dispelled upon secretion, we reasoned that mast cells
      contribute to Zn homeostasis in this area of the brain, as they are found in
      greatest numbers in and around the dentate gyrus. This line of evidence was
      tested by comparing Timm-stained hippocampal sections of mast cell-deficient
      C57BL/6-KitW-sh/W-sh (Sash-/-) mice to those of mast cell-containing wild type
      (Sash+/+) animals. Mast cell deficient mice were found to have significantly
      increased Timm-positive staining as compared to controls, reflecting an increase
      in labile or bioactive Zn in this region. As we observed no change in total brain
      Zn (protein-bound plus unbound Zn), these increases indicate that mast cells may
      serve to bind what would otherwise be excessive or deleterious levels of labile
      Zn, or that they are able to recruit metallothionein proteins. Because elevated
      levels of labile Zn are observed in the brains of patients with neurodegenerative
      diseases such as Alzheimer's, the potential contribution of mast cells to these
      diseases remains a compelling one. Overall, these data support a role for mast
      cells in either establishing or maintaining Zn homeostasis in the brain in the
      service of health, while Zn dysregulation has the potential to reduce learning,
      memory, and ultimately organismal survival.

PMID- 28445770
TI  - First evidence that waterborne methylphenidate alters endocrine and behavioral
      stress responses in zebrafish.
AB  - Several studies have reported the presence of methylphenidate (MPH) in effluents;
      however, its impacts on aquatic life are not yet well understood. Here, we
      investigated the effects of acute exposure on endocrine and behavioral stress
      responses to environmentally relevant concentrations of MPH in zebrafish. We show
      that MPH blunts the response of cortisol to stress in zebrafish. On the other
      hand, MPH stresses fish per se. Additionally, MPH seems to modulate anxiety-like
      behaviors. We conclude that the presence of MPH in aquatic environments can alter
      neuroendocrine and behavior responses, which might considerably impact fish
      survival and welfare.

PMID- 28445771
TI  - Cyclin-dependent kinase 5/Collapsin response mediator protein 2 pathway may
      mediate sevoflurane-induced dendritic development abnormalities in rat cortical
      neurons.
AB  - Sevoflurane has been reported to induce neurotoxicity and cognitive impairment in
      the developing brains. However, the underlying molecular mechanisms remain poorly
      understood. Recent studies have demonstrated aberrant cyclin-dependent kinase 5
      (CDK5) activity is implicated in inhaled anesthetic-induced neurotoxicity.
      CDK5/CRMP2 signaling is involved in the cortical and hippocampal dendritic
      development. The aim of present study is to investigate whether the CDK5/CRMP2
      pathway mediates sevoflurane-induced dendritic development abnormalities. Rat
      primary cortical neurons were treated with 4% sevoflurane for 6h, the CDK5
      inhibitor roscovitine or the vehicle (0.3% DMSO) was administered 12h before
      sevoflurane or carrying gases exposure. Cortical neurons were harvested for
      further analysis 0h, 12h and 24h after exposure. Sevoflurane exposure for 6h did
      not reduce cell viability and slightly increased the expression of cleaved
      caspase-3. Sevoflurane induced abnormal CDK5 activation by increasing the
      expression of its activator p25 and promoted the phosphorylation of CRMP2
      (Ser522). The increased phospho-CRMP2 (Ser522) was mainly distributed in the
      cytoplasm of cortical neurons. Sevoflurane significantly reduced the number of
      primary dendrites and the number of branching points; whereas it did not
      influence the total dendritic length. Suppression of CDK5 activation with
      roscovitine attenuated neuronal apoptosis, hyperphosphorylation of CRMP2 (Ser522)
      and dendritic development abnormalities induced by sevoflurane. Our results
      indicate that activation of the CDK5/CRMP2 pathway may mediate sevoflurane
      induced dendritic development abnormalities in the cortical neurons. The
      physiological significance of these findings remains to be determined.

PMID- 28445772
TI  - Rosiglitazone pretreatment influences thrombin-induced phagocytosis by rat
      microglia via activating PPARgamma and CD36.
AB  - OBJECTIVE: To explore the protective role of rosiglitazone against secondary
      brain injury after cerebral hemorrhage, we investigated the effect of
      rosiglitazone pretreatment on thrombin-induced microglial phagocytosis and
      described the molecular mechanisms involved in this process. METHODS: Primary
      microglial cells were obtained from the brain tissue of newborn Sprague-Dawley
      rats and were randomly divided into four groups: the normal, thrombin
      stimulation, thrombin-treated plus rosiglitazone, and thrombin-rosiglitazone plus
      proliferator-activated receptor-gamma (PPARgamma) antagonist groups. Microglial
      phagocytosis was measured using a laser scanning confocal microscope. The
      expression of PPARgamma and cluster of differentiation 36 (CD36) in each group
      was detected via quantitative reverse transcription-PCR and western blot
      analysis. RESULTS: The thrombin-treated plus rosiglitazone group showed a
      significant increase in phagocytic activity compared to the other groups
      (P<0.05), while the PPARgamma antagonist group significantly reduced microglial
      phagocytosis compared to the thrombin-treated plus rosiglitazone and the normal
      group. Moreover, the expression of PPARgamma and CD36 was considerably higher in
      the thrombin-treated plus rosiglitazone group than in the normal and the thrombin
      group. Nevertheless, the thrombin-rosiglitazone-PPARgamma group expressed a lower
      level of PPARgamma and CD36 compared to the thrombin-treated plus rosiglitazone
      group. CONCLUSION: Rosiglitazone can increase thrombin-induced microglial
      phagocytosis, by a mechanism possibly involved in the increase of PPARgamma and
      CD36 through the PPARgamma pathway, which may provide a new option for cerebral
      hemorrhage treatment.

PMID- 28445773
TI  - Taxonomic comments on Diphyllobothrium hottai Yazaki, Fukumoto & Abe, 1988
      (Cestoda: Diphyllobothriidae).

PMID- 28445774
TI  - VoxResNet: Deep voxelwise residual networks for brain segmentation from 3D MR
      images.
AB  - Segmentation of key brain tissues from 3D medical images is of great significance
      for brain disease diagnosis, progression assessment and monitoring of neurologic
      conditions. While manual segmentation is time-consuming, laborious, and
      subjective, automated segmentation is quite challenging due to the complicated
      anatomical environment of brain and the large variations of brain tissues. We
      propose a novel voxelwise residual network (VoxResNet) with a set of effective
      training schemes to cope with this challenging problem. The main merit of
      residual learning is that it can alleviate the degradation problem when training
      a deep network so that the performance gains achieved by increasing the network
      depth can be fully leveraged. With this technique, our VoxResNet is built with 25
      layers, and hence can generate more representative features to deal with the
      large variations of brain tissues than its rivals using hand-crafted features or
      shallower networks. In order to effectively train such a deep network with
      limited training data for brain segmentation, we seamlessly integrate multi
      modality and multi-level contextual information into our network, so that the
      complementary information of different modalities can be harnessed and features
      of different scales can be exploited. Furthermore, an auto-context version of the
      VoxResNet is proposed by combining the low-level image appearance features,
      implicit shape information, and high-level context together for further improving
      the segmentation performance. Extensive experiments on the well-known benchmark
      (i.e., MRBrainS) of brain segmentation from 3D magnetic resonance (MR) images
      corroborated the efficacy of the proposed VoxResNet. Our method achieved the
      first place in the challenge out of 37 competitors including several state-of-the
      art brain segmentation methods. Our method is inherently general and can be
      readily applied as a powerful tool to many brain-related studies, where accurate
      segmentation of brain structures is critical.

PMID- 28445775
TI  - Changes in social isolation and loneliness following total hip and knee
      arthroplasty: longitudinal analysis of the English Longitudinal Study of Ageing
      (ELSA) cohort.
AB  - OBJECTIVE: To determine the prevalence and change in social isolation and
      loneliness in people before and after total hip arthroplasty (THA) and total knee
      arthroplasty (TKA) in England. DESIGN: The English Longitudinal Study of Ageing
      (ELSA) dataset, a prospective study of community-dwelling older adults, was used
      to identify people who had undergone primary THA or TKA because of
      osteoarthritis. Social isolation was assessed using the ELSA Social Isolation
      Index. Loneliness was evaluated using the Revised University of California, Los
      Angeles (UCLA) Loneliness Scale. The prevalence of social isolation and
      loneliness were calculated and multilevel modelling was performed to assess the
      potential change of these measures before arthroplasty, within a two-year
      operative-recovery phase and a following two-year follow-up. RESULTS: The sample
      consisted of 393 people following THA and TKA. The prevalence of social isolation
      and loneliness changed from 16.9% to 18.8% pre-operative to 21.8% and 18.9% at
      the final post-operative follow-up respectively. This was not a statistically
      significant change for either measure (P = 0.15; P = 0.74). There was a
      significant difference in social isolation at the recovery phase compared to the
      pre-operative phase (P = 0.01), where people following arthroplasty reported an
      increase in social isolation (16.9-21.4%). There was no significant difference
      between the assessment phases in respect to UCLA Loneliness Scale score (P >=
      0.74). CONCLUSIONS: Given the negative physical and psychological consequences
      which social isolation and loneliness can have on individuals following THA or
      TKA, clinicians should be mindful of this health challenge for this population.
      The reported prevalence of social isolation and loneliness suggests this is an
      important issue.

PMID- 28445776
TI  - Antimicrobial resistance in the Bacteroides fragilis group in faecal samples from
      patients receiving broad-spectrum antibiotics.
AB  - Members of the Bacteroides fragilis group are opportunistic pathogens and cause
      severe infections including bacteraemia. As increased levels of antimicrobial
      resistance in B. fragilis group bacteria can be detected years after
      administration of specific antibiotics, monitoring antimicrobial susceptibility
      in the gut microbiota could be important. The objectives of this study were to 1)
      investigate the distribution of species and the occurrence of reduced
      antimicrobial susceptibility in the B. fragilis group from patients treated at
      departments with a high level of antibiotic use, 2) to determine the prevalence
      of the carbapenem resistance gene cfiA in B. fragilis in this patient group, and
      3) to determine the association between previous antibiotic treatment and reduced
      susceptibility to clindamycin, meropenem, metronidazole, and piperacillin
      tazobactam. Consecutive faecal samples (n = 197) were collected from patients at
      the departments of haematology, oncology, and infectious diseases at Odense
      University Hospital, Denmark. Three colonies from each sample were identified by
      Matrix Assisted Lazer Desorption Ionization Time of Flight Mass Spectrometry and
      isolates were screened for resistance to clindamycin, meropenem, metronidazole,
      and piperacillin-tazobactam. B. fragilis isolates were tested for the cfiA
      metallo-beta-lactamase gene. Fisher's Exact test was used to test for correlation
      between antimicrobial exposure and reduced susceptibility. A total of 359
      isolates were tested for reduced susceptibility. Of these 28%, 5%, <1%, and 11%
      were intermediate susceptible or resistant to clindamycin, meropenem,
      metronidazole, and piperacillin-tazobactam respectively. Three metronidazole
      resistant Bacteroides spp. were isolated. The proportion of B. fragilis belonging
      to division II (cfiA+) was 5.3%. Previous exposure to meropenem was associated
      with reduced susceptibility to meropenem (p= 0.001). In conclusion, antimicrobial
      resistance is prevalent and the distribution of species appears to be affected in
      the B. fragilis group from patients receiving broad-spectrum antibiotics, with
      meropenem exposure being associated with meropenem resistance.

PMID- 28445777
TI  - Five-Year Follow-Up After Laparoscopic Large Nerve Resection for Deep
      Infiltrating Sciatic Nerve Endometriosis.
AB  - OBJECTIVE: To report neurologic follow-up of patients after laparoscopic large
      resection of deep infiltrating endometriosis of the sciatic nerve. DESIGN:
      Prospective clinical case series. SETTING: Tertiary referral unit specializing in
      advanced gynecologic surgery and neuropelveology. PATIENTS: All data for patients
      who underwent laparoscopic surgery for endometriosis of the sciatic nerve between
      2004 and 2016 (n = 259) were documented prospectively. In this study, patients
      who underwent a large resection of the sciatic nerve (>30% of the nerve) and were
      followed for at least 5 years were evaluated (n = 46). All patients presented
      preoperatively with incapacity for normal gait and foot drop. All were suffering
      from intractable and constant neuropathic sciatic pain (visual analog scale [VAS]
      score of 9 to 10 despite strong pain medicine), with sensorimotor disorders of
      the affected leg. INTERVENTIONS: Laparoscopic large resection of endometriosis of
      the sciatic nerve. MEASUREMENTS AND MAIN RESULTS: All procedures were performed
      by laparoscopy. Postoperative management included medical treatment with
      neuroleptic agents and intensive physiotherapy. At the 5-year follow-up, all
      patients reported significant pain reduction, with a median VAS score of 2.1
      (range, 0 to 3) and recovery of normal gait, including the ability to climb
      stairs. CONCLUSION: In deep infiltrating intraneural endometriosis of the sciatic
      nerve, patients present with motor disorders before and after surgical resection.
      The average VAS score was reduced from 9.33 preoperatively to 1.25 at a 3-year
      follow-up. When full resection of endometriosis including nerve resection is
      completed, sciatic nerve function recover, but recovery of a normal gait may take
      at least 3 years and intensive physiotherapy.

PMID- 28445778
TI  - The impact of bilateral vagotomy on the physostigmine-induced airway constriction
      in ferrets.
AB  - Vagal innervations have a great role in the respiratory function and are the main
      route of signal transmission from respiratory neural centers into the trachea and
      others conducting airways. We have investigated the role of central mechanisms
      related to vagal neural pathways and the cholinergic outflow in tracheobronchial
      smooth muscle tone and lung mechanics parameters. Parameters of lung mechanics
      such as lung resistance (RL), dynamic compliance (Cdyn) and pressure in bypassed
      tracheal segment (Ptseg) were measured before and after vagotomy and asphyxia
      test. Before vagotomy (BV), the control measurements were obtained and
      physostigmine was administered systemically, in increasing dose 10, 40 and
      100MUg/kg body weight (bw) with 15min interval between doses. After vagotomy
      (AV), administration of physostigmine with the same doses as BV has been done and
      the asphyxia challenge was conducted as per study protocol. The values of Ptseg
      and RL after physostigmine administration, BV vs. AV, respectively, at maximal
      dose of 100MUg/kg bw were 32.5+/-3.3cm H2O, and 10.6+/-1.5cm H2O (p<0.0001);
      0.16+/-0.04cm H2O/mL/s, and 0.067+/-0.006cm H2O/mL/s AV (P<0.05). The Cydn values
      were affected after physostigmine administration only at the lowest dose of
      10MUg/kg bw, and BV was 0.75+/-0.05mL/cm H2O vs. 0.53+/-0.04mL/cm H2O AV
      (P<0.004). Cholinergic outflow produced increases in tracheal tone, lung
      resistance and a decrease in dynamic compliance before, but not after vagotomy.
      Our results show the high impact of central neuronal mechanism in parameters of
      lung mechanics and respiration. This study indicates that vagal nerves have a
      crucial role, in the transmission of impulses initiated from central nervous
      system, in regulating the respiration by contraction or relaxation of airway
      smooth muscle tone.

PMID- 28445779
TI  - The acute cardiorespiratory effects of centrally injected arachidonic acid; the
      mediation of prostaglandin E, D and F2alpha.
AB  - Arachidonic acid (AA), which is released from synaptic membrane phospholipid by
      neuroreceptor-initiated activation of phospholipase A2, is abundant in the brain
      and works as a neurotransmitter and/or neuromodulator in the central nervous
      system. Recently we reported that centrally injected AA generated pressor and
      hyperventilation effects by activating thromboxane A2 (TXA2) signaling pathway.
      The present study was designed to investigate the mediation of other metabolites
      of AA such as prostaglandin (PG) D, PGE and PGF2alpha alongside TXA2 in the AA
      evoked cardiorespiratory effects in anaesthetized rats. Intracerebroventricular
      (i.c.v.) administration of AA caused pressor, bradycardic and hyperventilation
      responses by increasing pO2 and decreasing pCO2 in adult male anaesthetized
      Sprague Dawley rats. Pretreatment (i.c.v) with different doses of DP/EP
      prostanoid receptor antagonist, AH6809 or FP prostanoid receptor antagonist,
      PGF2alpha dimethylamine partially blocked the cardiorespiratory and blood gas
      changes induced by AA. In conclusion, these data plainly report that central PGD,
      PGE or PGF2alpha might mediate, at least partly, centrally administered AA-evoked
      cardiorespiratory and blood gas responses.

PMID- 28445782
TI  - The immunohistochemical distribution of the GABAA receptor alpha1, alpha2,
      alpha3, beta2/3 and gamma2 subunits in the human thalamus.
AB  - The GABAA receptor is the most abundant inhibitory receptor in the human brain
      and is assembled from a variety of different subunit subtypes which determines
      their pharmacology and physiology. To determine which GABAA receptor subunit
      proteins are found in the human thalamus we investigated the distribution of five
      major GABAA receptor subunits alpha1, alpha2, alpha3, beta2,3 and gamma2 using
      immunohistochemical techniques. The alpha1-, beta2,3- and gamma2- subunits which
      combine to form a benzodiazepine sensitive GABAA receptor showed the most intense
      levels of staining and were the most common subunits found throughout the human
      thalamus especially in the ventral and posterior nuclear groups. The next most
      intense staining was for the alpha3-subunit followed by the alpha2-subunit. The
      intralaminar nuclear group, the mediodorsal nucleus and the thalamic reticular
      nucleus contained alpha1-, beta2,3- and gamma2- subunits staining as well as the
      highest levels of the alpha2- and alpha3- subunits. The sensory dorsal lateral
      geniculate nucleus contained very high levels of alpha1- and beta2,3- and gamma2
      subunits. The highest densities of GABAA receptors found throughout the thalamus
      which contained the subunits alpha1, beta2,3, and gamma2 included nuclei which
      are especially involved in the control or the modulation of the cortico-basal
      ganglia-thalamo-cortical motor circuits and are thus important in disorders such
      as Huntington's disease where the GABAergic projections of the basal ganglia are
      compromised. In addition the majority of receptors in the thalamic reticular
      nucleus contain alpha3 and gamma2 subunits whilst the intralaminar nuclei contain
      high levels of alpha2 and alpha3 subunits.

PMID- 28445780
TI  - Mitochondrial ribosomes in cancer.
AB  - Mitochondria play fundamental roles in the regulation of life and death of
      eukaryotic cells. They mediate aerobic energy conversion through the oxidative
      phosphorylation (OXPHOS) system, and harbor and control the intrinsic pathway of
      apoptosis. As a descendant of a bacterial endosymbiont, mitochondria retain a
      vestige of their original genome (mtDNA), and its corresponding full gene
      expression machinery. Proteins encoded in the mtDNA, all components of the
      multimeric OXPHOS enzymes, are synthesized in specialized mitochondrial ribosomes
      (mitoribosomes). Mitoribosomes are therefore essential in the regulation of
      cellular respiration. Additionally, an increasing body of literature has been
      reporting an alternative role for several mitochondrial ribosomal proteins as
      apoptosis-inducing factors. No surprisingly, the expression of genes encoding for
      mitoribosomal proteins, mitoribosome assembly factors and mitochondrial
      translation factors is modified in numerous cancers, a trait that has been linked
      to tumorigenesis and metastasis. In this article, we will review the current
      knowledge regarding the dual function of mitoribosome components in protein
      synthesis and apoptosis and their association with cancer susceptibility and
      development. We will also highlight recent developments in targeting
      mitochondrial ribosomes for the treatment of cancer.

PMID- 28445781
TI  - Mitochondrial ROS control of cancer.
AB  - Mitochondria serves a primary role in energy maintenance but also function to
      govern levels of mitochondria-derived reactive oxygen species (mROS). ROS have
      long been established to play a critical role in tumorigenesis and are now
      considered to be integral to the regulation of diverse signaling networks that
      drive proliferation, tumor cell survival and malignant progression. mROS can
      damage DNA, activate oncogenes, block the function of tumor suppressors and drive
      migratory signaling. The mitochondrion's oxidant scavenging systems including
      SOD2, Grx2, GPrx, Trx and TrxR are key of the cellular redox tone. These
      mitochondrial antioxidant systems serve to tightly control the levels of the
      primary ROS signaling species, H2O2. The coordinated control of mROS levels is
      also coupled to the activity of the primary H2O2 consuming enzymes of the
      mitochondria which are reliant on the epitranscriptomic control of selenocysteine
      incorporation. This review highlights the interplay between these many oncogenic
      signaling networks, mROS and the H2O2 emitting and consuming capacity of the
      mitochondria.

PMID- 28445783
TI  - Jump starting shared medical appointments for diabetes with weight management:
      Rationale and design of a randomized controlled trial.
AB  - BACKGROUND: Rates of glycemic control remain suboptimal nationwide. Medication
      intensification for diabetes can have undesirable side effects (weight gain,
      hypoglycemia), which offset the benefits of glycemic control. A Shared Medical
      Appointment (SMA) intervention for diabetes that emphasizes weight management
      could improve glycemic outcomes and reduce weight while simultaneously lowering
      diabetes medication needs, resulting in less hypoglycemia and better quality of
      life. We describe the rationale and design for a study evaluating a novel SMA
      intervention for diabetes that primarily emphasizes low-carbohydrate diet-focused
      weight management. METHODS: Jump Starting Shared Medical Appointments for
      Diabetes with Weight Management (Jump Start) is a randomized, controlled trial
      that is allocating overweight Veterans (body mass index>=27kg/m2) with type 2
      diabetes into two arms: 1) a traditional SMA group focusing on medication
      management and self-management counseling; or 2) an SMA group that combines low
      carbohydrate diet-focused weight management (WM/SMA) with medication management.
      Hemoglobin A1c reduction at 48weeks is the primary outcome. Secondary outcomes
      include hypoglycemic events, diabetes medication use, weight, medication
      adherence, diabetes-related quality of life, and cost-effectiveness. We
      hypothesize that WM/SMA will be non-inferior to standard SMA for glycemic
      control, and will reduce hypoglycemia, diabetes medication use, and weight
      relative to standard SMA, while also improving quality of life and costs.
      CONCLUSIONS: Jump Start targets two common problems that are closely related but
      infrequently managed together: diabetes and obesity. By focusing on diet and
      weight loss as the primary means to control diabetes, this intervention may
      improve several meaningful patient-centered outcomes related to diabetes.

PMID- 28445784
TI  - Brain potentials predict language selection before speech onset in bilinguals.
AB  - Studies of language production in bilinguals have seldom considered the fact that
      language selection likely involves proactive control. Here, we show that Chinese
      English bilinguals actively inhibit the language not-to-be used before the onset
      of a picture to be named. Depending on the nature of a directive cue,
      participants named a subsequent picture in their native language, in their second
      language, or remained silent. The cue elicited a contingent negative variation of
      event-related brain potentials, greater in amplitude when the cue announced a
      naming trial as compared to when it announced a silent trial. In addition, the
      negativity was greater in amplitude when the picture was to be named in English
      than in Chinese, suggesting that preparation for speech in the second language
      requires more inhibition than preparation for speech in the native language. This
      result is the first direct neurophysiological evidence consistent with proactive
      inhibitory control in bilingual production.

PMID- 28445786
TI  - Metallo-beta-lactamase inhibitors by bioisosteric replacement: Preparation,
      activity and binding.
AB  - Bacterial resistance is compromising the use of beta-lactam antibiotics including
      carbapenems. The main resistance mechanism against beta-lactams is hydrolysis of
      the beta-lactam ring mediated by serine- or metallo-beta-lactamases (MBLs).
      Although several inhibitors of MBLs have been reported, none has been developed
      into a clinically useful inhibitor. Mercaptocarboxylic acids are among the most
      prominent scaffolds reported as MBL inhibitors. In this study, the carboxylate
      group of mercaptocarboxylic acids was replaced with bioisosteric groups like
      phosphonate esters, phosphonic acids and NH-tetrazoles. The influence of the
      replacement on the bioactivity and inhibitor binding was evaluated. A series of
      bioisosteres of previously reported inhibitors was synthesized and evaluated
      against the MBLs VIM-2, NDM-1 and GIM-1. The most active inhibitors combined a
      mercapto group and a phosphonate ester or acid, with two/three carbon chains
      connecting a phenyl group. Surprisingly, also compounds containing thioacetate
      groups instead of thiols showed low IC50 values. High-resolution crystal
      structures of three inhibitors in complex with VIM-2 revealed hydrophobic
      interactions for the diethyl groups in the phosphonate ester (inhibitor 2b), the
      mercapto bridging the two active site zinc ions, and tight stacking of the
      benzene ring to the inhibitor between Phe62, Tyr67, Arg228 and His263. The
      inhibitors show reduced enzyme activity in Escherichia coli cells harboring MBL.
      The obtained results will be useful for further structural guided design of MBL
      inhibitors.

PMID- 28445787
TI  - Adipose-derived stem cells were impaired in restricting CD4+T cell proliferation
      and polarization in type 2 diabetic ApoE-/- mouse.
AB  - BACKGROUND: Atherosclerosis (AS) is the most common and serious complication of
      type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic
      inflammation rather than hyperglycemia. Adipose tissue is the major source of
      systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4+T cells
      play pivotal role in promoting adipose inflammation. Adipose-derived stem cells
      (ADSCs) for fat regeneration have potent ability of immunosuppression and
      restricting CD4+T cells as well. Whether T2DM ADSCs are impaired in antagonizing
      CD4+T cell proliferation and polarization remains unclear. METHODS: We
      constructed type 2 diabetic ApoE-/- mouse models and tested infiltration and
      subgroups of CD4+T cell in stromal-vascular fraction (SVF) in vivo. Normal/T2DM
      ADSCs and normal splenocytes with or without CD4 sorting were separated and co
      cultured at different scales ex vivo. Immune phenotypes of pro- and anti
      inflammation of ADSCs were also investigated. Flow cytometry (FCM) and ELISA were
      applied in the experiments above. RESULTS: CD4+T cells performed a more pro
      inflammatory phenotype in adipose tissue in T2DM ApoE-/- mice in vivo.
      Restriction to CD4+T cell proliferation and polarization was manifested obviously
      weakened after co-cultured with T2DM ADSCs ex vivo. No obvious distinctions were
      found in morphology and growth type of both ADSCs. However, T2DM ADSCs acquired a
      pro-inflammatory immune phenotype, with secreting less PGE2 and expressing higher
      MHC-II and co-stimulatory molecules (CD40, CD80). Normal ADSCs could also obtain
      the phenotypic change after cultured with T2DM SVF supernatant. CONCLUSION: CD4+T
      cell infiltration and pro-inflammatory polarization exist in adipose tissue in
      type 2 diabetic ApoE-/- mice. T2DM ADSCs had impaired function in restricting
      CD4+T lymphocyte proliferation and pro-inflammatory polarization due to immune
      phenotypic changes.

PMID- 28445785
TI  - Staphylococcus aureus pore-forming toxins: The interface of pathogen and host
      complexity.
AB  - Staphylococcus aureus is a prominent human pathogen capable of infecting a
      variety of host species and tissue sites. This versatility stems from the
      pathogen's ability to secrete diverse host-damaging virulence factors. Among
      these factors, the S. aureus pore-forming toxins (PFTs) alpha-toxin and the
      bicomponent leukocidins, have garnered much attention for their ability to lyse
      cells at low concentrations and modulate disease severity. Although many of these
      toxins were discovered nearly a century ago, their host cell specificities have
      only been elucidated over the past five to six years, starting with the discovery
      of the eukaryotic receptor for alpha-toxin and rapidly followed by identification
      of the leukocidin receptors. The identification of these receptors has revealed
      the species- and cell type-specificity of toxin binding, and provided insight
      into non-lytic effects of PFT intoxication that contribute to disease
      pathogenesis.

PMID- 28445789
TI  - Characterisation of Pb-induced changes and prediction of Pb exposure in
      microalgae using infrared spectroscopy.
AB  - Macromolecular changes in Chlorella sp. FleB1 and Scenedesmus acutus YaA6 exposed
      to Pb were characterised by Attenuated Total Reflectance-Fourier Transform
      Infrared (ATR-FTIR) spectroscopy. Spectra were collected in the mid-infrared
      spectral region and a chemometric approach was used to analyse the spectra.
      Principal Component Analysis showed that under Pb treatment, carbohydrates and
      lipids increased while proteins and phosphorylated molecules decreased in both
      the isolates. These conclusions were corroborated by conventional measurements of
      photosynthesis and neutral lipids. In the two strains, Pb inhibited
      photosynthesis, which directly affects the synthesis of polysaccharides and other
      macromolecules. Neutral lipids as measured by Nile Red were increased in lead
      treated samples. Modelling of spectral data against Pb exposure levels allowed Pb
      exposed samples to be readily discriminated from unexposed controls and the level
      of Pb exposure could be predicted with good accuracy in independent validation
      testing. This study demonstrates the utility of the spectroscopic approach as a
      rapid, inexpensive, non-destructive method to understand changes in cellular
      composition induced by Pb and allowing detection and quantification of Pb levels
      in metal-contaminated cells in a "snapshot".

PMID- 28445788
TI  - An emerging role for the ribosome as a nexus for post-translational
      modifications.
AB  - The ribosome is one of life's most ancient molecular machines that has
      historically been viewed as a backstage participant in gene regulation,
      translating the genetic code across all kingdoms of life in a rote-like fashion.
      However, recent studies suggest that intrinsic components of the ribosome can be
      regulated and diversified as a means to intricately control the expression of the
      cellular proteome. In this review, we discuss advances in the characterization of
      ribosome post-translational modifications (PTMs) from past to present. We
      specifically focus on emerging examples of ribosome phosphorylation and
      ubiquitylation, which are beginning to showcase that PTMs of the ribosome are
      versatile, may have functional consequences for translational control, and are
      intimately linked to human disease. We further highlight the key questions that
      remain to be addressed to gain a more complete picture of the array of ribosome
      PTMs and the upstream enzymes that control them, which may endow ribosomes with
      greater regulatory potential in gene regulation and control of cellular
      homeostasis.

PMID- 28445790
TI  - Improving insomnia in primary care patients: A randomized controlled trial of
      nurse-led group treatment.
AB  - BACKGROUND: Insomnia is a common health problem, and most people who seek help
      for insomnia consult primary care. In primary care, insomnia treatment typically
      consists of hypnotic drugs, although cognitive behavioral therapy for insomnia is
      the recommended treatment. However, such treatment is currently available to few
      primary care patients. OBJECTIVES: To evaluate the effects of a group treatment
      program for insomnia led by nurses in primary care. OUTCOMES: were the Insomnia
      Severity Index, a 2-week sleep diary, and a questionnaire on frequency of
      hypnotic drug use. DESIGN: A randomized controlled trial with pre- and post
      treatment assessment and a 1-year post-treatment follow-up of the intervention
      group. SETTINGS: Routine primary health care; 7 primary care centers in
      Stockholm, Sweden. PARTICIPANTS: Patients consulting primary care for insomnia
      were assessed for eligibility. To be included, patients had to have insomnia
      disorder and be 18 years or older. Patients were excluded if they if they worked
      night shifts or had severe untreated somatic and/or mental illness, bipolar
      disorder, or untreated sleep disorder other than insomnia. One-hundred and sixty
      five patients 20 to 90 years were included. Most were women, and many had co
      existing somatic and/or mental health problems. The post-treatment dropout rate
      was 20%. METHODS: The intervention was a nurse-led group treatment for insomnia
      based on the techniques of cognitive behavioral therapy for insomnia. The nurses
      had 2days of training in how to deliver the program. Ninety patients were
      randomized to the intervention and 75 to the control group (treatment as usual).
      Data from 82 in the intervention and 71 in the control group were analyzed in
      accordance with intention-to-treat principles. Fifty-four of the 72 in the
      intervention group who participated in the group treatment program were followed
      up after 1year. RESULTS: Mean Insomnia Severity Index score decreased
      significantly from 18.4 to 10.7 after group treatment but remained unchanged
      after treatment as usual (17.0 to 16.6). The effect size was large (1.23). Group
      treatment also resulted in significant improvements in all sleep diary variables
      (sleep onset latency, total sleep time, time awake after sleep onset, number of
      awakenings, and sleep quality). It also reduced hypnotic drug use. Improvements
      were maintained 1-year post-treatment. CONCLUSIONS: Patients with insomnia can be
      treated successfully with a nurse-led group treatment program in primary health
      care. The results support implementation of the treatment program, particularly
      given the need for increased access to non-pharmacological insomnia treatments.

PMID- 28445791
TI  - Quality and relevance of master degree education for the professional development
      of nurses and midwives.
AB  - BACKGROUND: Advanced education in nursing is essential to provide safe, high
      quality and efficient health services in line with population needs. However,
      there is an almost complete lack of studies on how nurses view the usefulness of
      post-graduate education for their current employment and for professional
      advancement. OBJECTIVES: To evaluate how nurse graduates view the quality,
      relevance and applicability of the knowledge and skills acquired during the
      Master of Science in Nursing (MSN) degree. DESIGN: Multicentre cross-sectional
      study. METHODS: A multicenter cross-sectional study was carried out through an
      online questionnaire mailed (July 2014-June 2015) to 560 nurses who obtained the
      MSN degree from 23 Italian universities in the academic year 2010-2011.
      DISCUSSION: A total of 426 nurses completed the survey (response rate 76.1%), 80%
      of whom believed they had acquired knowledge and skills useful in their
      professional life after graduation. A multiple logistic regression model
      highlighted the characteristics of nurse graduates who judged the master's course
      relevant for their present role. In brief, they are expert nurses (OR=3.41, 95%
      CI=1.54-7.54) who achieved professional growth after the course (OR=5.25, 95%
      CI=2.67-10.33) and who judged the course very good or excellent (OR=2.16, 95%
      CI=1.04-4.52). Only 8% of the respondents achieved a full professional growth
      after the course. CONCLUSION: In Italy, MSN courses are able to provide a high
      level of skills and competencies. However, given the low rate of professional
      growth after the course, specific policies should increase the employment rates
      of new master's graduate nurses.

PMID- 28445792
TI  - Vitamin D supplementation restores the blunted muscle protein synthesis response
      in deficient old rats through an impact on ectopic fat deposition.
AB  - We investigated the impact of vitamin D deficiency and repletion on muscle
      anabolism in old rats. Animals were fed a control (1 IU vitamin D3/g, ctrl, n=20)
      or a vitamin D-depleted diet (VDD; 0 IU, n=30) for 6 months. A subset was
      thereafter sacrificed in the control (ctrl6) and depleted groups (VDD6).
      Remaining control animals were kept for 3 additional months on the same diet
      (ctrl9), while a part of VDD rats continued on a depleted diet (VDD9) and another
      part was supplemented with vitamin D (5 IU, VDS9). The ctr16 and VDD6 rats and
      the ctr19, VDD9 and VDS9 rats were 21 and 24 months old, respectively. Vitamin D
      status, body weight and composition, muscle strength, weight and lipid content
      were evaluated. Muscle protein synthesis rate (fractional synthesis rate; FSR)
      and the activation of controlling pathways were measured. VDD reduced plasma
      25(OH)-vitamin D, reaching deficiency (<25 nM), while 25(OH)-vitamin D increased
      to 118 nM in the VDS group (P<.0001). VDD animals gained weight (P<.05) with no
      corresponding changes in lean mass or muscle strength. Weight gain was associated
      with an increase in fat mass (+63%, P<.05), intramyocellular lipids (+75%, P<.05)
      and a trend toward a decreased plantaris weight (-19%, P=.12). Muscle FSR
      decreased by 40% in the VDD group (P<.001), but was restored by vitamin D
      supplementation (+70%, P<.0001). Such changes were linked to an over
      phosphorylation of eIF2alpha. In conclusion, vitamin D deficiency in old rats
      increases adiposity and leads to reduced muscle protein synthesis through
      activation of eIF2alpha. These disorders are restored by vitamin D
      supplementation.

PMID- 28445793
TI  - Predictors of 30-Day Pulmonary Complications after Outpatient Surgery: Relative
      Importance of Body Mass Index Weight Classifications in Risk Assessment.
AB  - BACKGROUND: Current literature is controversial regarding the importance of obese
      BMI classifications as a risk factor for pulmonary complications after outpatient
      surgery. The objective of the current investigation was to evaluate predictors of
      pulmonary outcomes after outpatient surgery and to assess the importance of BMI
      weight classifications in risk assessment. STUDY DESIGN: Patients with
      "outpatient" recorded as their inpatient/outpatient status in the 2012 to 2013
      NSQIP database were included. The primary outcome of interest was the occurrence
      of a new pulmonary complication (eg pneumonia, pulmonary embolism, unplanned
      intubation, or ventilator-assisted respiration for greater than 48 hours) within
      30 days of surgery. RESULTS: There were 444,532 cases included in the final
      analysis. There were 996 (0.22%; 99% CI 0.21% to 0.24%) all-cause pulmonary
      complications. Binary logistic regression identified BMI as an independent
      predictor of a pulmonary complication, unadjusted odds ratio 1.091 (99.75% CI
      1.026 to 1.160) per 5 kg/m2 change in BMI, p < 0.001. Adjusted odds of a
      pulmonary complication with a BMI of 35 to 39.99 kg/m2 was 1.44 (99.75% CI 1.01
      to 2.06; p = 0.002) and with a BMI of 40 to 49.99 kg/m2 was 1.68 (99.75% CI 1.13
      to 2.50; p < 0.001) compared with a BMI of 18.5 to 24.99 kg/m2. CONCLUSIONS:
      Obese classes II and III were associated with an independent risk of a pulmonary
      complication. The risk associated with obesity was low compared with the risk
      associated with advanced age, prolonged surgical duration, and the risk of
      comorbidities including congestive heart failure, COPD, and renal failure.

PMID- 28445794
TI  - Post-Transplant Malignancy after Pediatric Kidney Transplantation: Retrospective
      Analysis of Incidence and Risk Factors in 884 Patients Receiving Transplants
      Between 1963 and 2015 at the University of Minnesota.
AB  - BACKGROUND: Post-transplant malignancy (PTM) remains a concern among pediatric
      kidney transplant (PKT) recipients. STUDY DESIGN: Between 1963 and 2015, 884
      pediatric (age 0 to 17 years old) patients received 1,055 PKTs at our
      institution. Cox proportional hazards models were constructed to identify risk
      factors for PTM after PKT with time-to-first-PTM as a primary outcome. Secondly,
      the hazard of death or graft loss was calculated in patients who developed PTM.
      RESULTS: Median patient survival was 33 years (interquartile range [IQR] 18.7 to
      47 years); 260 patients died during the study period and 47 had been diagnosed
      with PTM. There were 235 PTMs that occurred in 136 (15.4%) recipients at a median
      age of 29 years (IQR 17.8 to 37 years). The percentages of patients with PTM were
      13% at 20 years post-PKT and 26% at 30 years post-PKT. Of PTM patients who died,
      63.8% died of PTM. Among those who developed PTM, there was a higher hazard of
      death or graft loss (hazard ratio [HR] 1.62; 95% CI 1.11 to 2.38). In
      multivariable proportional hazards models, factors associated with PTM were
      increasing age at PKT (adjusted HR [AHR] 3.14; 95% CI 1.80 to 5.48 for 14 to 17
      year-olds compared with children less than 3 years), having a living unrelated
      donor (LURD; AHR 3.25; 95% CI 1.27 to 8.35 compared with a living related donor),
      or implanting an Epstein-Barr virus (EBV)-positive allograft in an EBV-negative
      recipient (AHR 5.66; 95% CI 1.11 to 29.0). Compared with the general population,
      the cancer rate for PKT recipients was 6 times higher (126 vs 21 per 100,000
      person-years). CONCLUSIONS: Pediatric kidney transplant recipients are at
      increased risk of PTM, which adversely affects survival. Children receiving
      transplants at an older age, from a LURD, or who receive an EBV-positive organ,
      should be monitored closely for the development of PTM.

PMID- 28445795
TI  - A Novel Approach to Calculating Small Intestine Length Based on Magnetic
      Resonance Enterography.
AB  - BACKGROUND: Bowel length is an important factor in the management of patients
      with intestinal failure and short bowel syndrome. However, it is difficult to
      accurately measure the length of the small intestine. Our aim was to demonstrate
      the feasibility of a dedicated software algorithm for calculating small intestine
      length based on magnetic resonance enterography (MRE) images. STUDY DESIGN: A
      custom algorithm for image thresholding, wall identification, segmentation, and
      path extraction was designed and implemented. Algorithm output included the
      Euclidean distance from the pylorus to the terminal ileum and coordinates of
      points along that route. For validation, 10 C57BL/6 mice underwent bowel
      preparation before MRE. After sacrifice, the entire small bowel was removed and
      the ex vivo small intestine length was measured in a standardized manner.
      Calculated and ex vivo length measurements were compared. RESULTS: Mean absolute
      difference and mean percentage difference between the 2 modalities were 1.8 +/-
      3.8 cm (p = 0.24) and 9.4% +/- 6.0%, respectively. CONCLUSIONS: This study
      demonstrates the feasibility of a dedicated, computer-vision-based algorithm that
      can reliably and accurately calculate the length of the small intestine using MRE
      images. A validated, noninvasive approach to measuring small intestine length
      that can be implemented using available clinical imaging can have a dramatic
      clinical impact on management in patients with short bowel syndrome, Crohn's
      disease, and other intestinal disorders.

PMID- 28445797
TI  - Development of a Clinically Actionable Incisional Hernia Risk Model after
      Colectomy Using the Healthcare Cost and Utilization Project.
AB  - BACKGROUND: Incisional hernia remains a persistent and burdensome complication
      after colectomy. Through individualized risk-assessment and prediction models, we
      aimed to improve preoperative risk counseling for patients undergoing colectomy;
      identify modifiable preoperative risk factors; and encourage the use of evidence
      based risk-prediction instruments in the clinical setting. STUDY DESIGN: A
      retrospective review of the Healthcare Cost and Utilization Project data was
      conducted for all patients undergoing either open or laparoscopic colectomy as
      identified through the state inpatient databases of California, Florida, and New
      York in 2009. Incidence of incisional hernia repair was collected from both the
      state inpatient databases and the state ambulatory surgery and services databases
      in the 3 states between index surgery and 2011. Hernia risk was calculated with
      multivariable hierarchical logistic regression modeling and validated using
      bootstrapping techniques. Exclusion criteria included concurrent hernia,
      metastasis, mortality, and age younger than 18 years. Inflation-adjusted
      expenditure estimates were calculated. RESULTS: Overall, 30,741 patients
      underwent colectomy, one-third of these procedures performed laparoscopically.
      Incisional hernia repair was performed in 2,563 patients (8.3%) (27-month follow
      up). Fourteen significant risk factors were identified, including open surgery
      (odds ratio = 1.49; p < 0.0001), obesity (odds ratio = 1.49; p < 0.0001), and
      alcohol abuse (odds ratio = 1.39; p = 0.010). Extreme-risk patients experienced
      the highest incidence of incisional hernia (19.8%) vs low-risk patients (3.9%) (C
      statistic = 0.67). CONCLUSIONS: We present a clinically actionable model of
      incisional hernia using all-payer claims after colectomy. The data presented can
      structure preoperative risk counseling, identify modifiable patient-specific risk
      factors, and advance the field of risk prediction using claims data.

PMID- 28445796
TI  - Decreasing the Use of Damage Control Laparotomy in Trauma: A Quality Improvement
      Project.
AB  - BACKGROUND: Our institution has published damage control laparotomy (DCL) rates
      of 30% and documented the substantial morbidity associated with the open abdomen.
      The purpose of this quality improvement (QI) project was to decrease the rate of
      DCL at a busy, Level I trauma center in the US. STUDY DESIGN: A prospective
      cohort of all emergent trauma laparotomies from November 2013 to October 2015 (QI
      group) was followed. The QI intervention was multifaceted and included audit and
      feedback for every DCL case. Morbidity and mortality of the QI patients were
      compared with those from a published control (control group: emergent laparotomy
      from January 2011 to October 2013). RESULTS: A significant decrease was observed
      immediately on beginning the QI project, from a 39% DCL rate in the control
      period to 23% in the QI group (p < 0.001). This decrease was sustained over the 2
      year study period. There were no differences in demographics, Injury Severity
      Score, or transfusions between the groups. No differences organ/space infection
      (control 16% vs QI 12%; p = 0.15), fascial dehiscence (6% vs 8%; p = 0.20),
      unplanned relaparotomy (11% vs 10%; p = 0.58), or mortality (9% vs 10%; p = 0.69)
      were observed. The reduction in use resulted in a decrease of 68 DCLs over the 2
      year period. There was a further reduction in the rate of DCL to 17% after
      completion of the QI project. CONCLUSIONS: A QI initiative rapidly changed the
      use of DCL and improved quality of care by decreasing resource use without an
      increase morbidity or mortality. This decrease was sustained during the QI period
      and further improved upon after its completion.

PMID- 28445798
TI  - Episiotomy: What angle do you cut to the midline?
AB  - OBJECTIVE: Although episiotomies are the commonest obstetric procedure performed
      the technique of performing one varies amongst obstetricians and midwives. The
      angle of episiotomy to the midline in particular has been shown to influence the
      risk of developing obstetric anal sphincter injuries (OASIS). In order to
      identify the differences in technique and to identify targets for training we
      undertook a practice survey of episiotomies to analyse the differences in
      technique between grades of obstetricians and midwives. STUDY DESIGN: A
      prospective practice survey of staff working on delivery suite in a tertiary
      referral unit with 9000 deliveries/year was conducted between 01/10/2014 to
      01/03/2015. Each participant was provided with a pictoral representation of a
      perineum and a pair of standard episiotomy scissors and asked to perform an
      episiotomy as per their usual practice. The profession and grade of each
      participant was recorded along with information regarding the incision including
      the angle to the midline, length of incision and lateral starting distance from
      the midline. One way ANOVA (unrelated) was used to perform statistical analysis
      using IBM SPSS v23. RESULTS: 101 staff members participated in the practice
      survey including 63 midwives, 9 junior trainees, 15 senior trainees and 14
      consultants. The mean angle of incision to the midline of episiotomies was 47
      degrees , 51 degrees , 66 degrees  and 77 degrees  for midwives, junior trainees,
      senior trainees and consultants respectively. The mean angle of incision
      performed by midwives was significantly different to senior trainees (p>0.01) and
      consultants (p<0.01). 45% of all episiotomies undertaken by midwives were done at
      an angle <45 degrees  to the midline, compared to 7% by senior trainees and none
      by consultants. CONCLUSIONS: This study identified clear deficiencies in the
      performance of episiotomies amongst obstetric trainees and midwives. Both
      midwives and obstetric trainees need to improve their technique if episiotomies
      are going to influence the incidence of OASIS and, more importantly the
      development of faecal incontinence. These results should be used to inform future
      training programmes to reduce the risks of OASIS.

PMID- 28445800
TI  - Adjunctive celecoxib for schizophrenia: A meta-analysis of randomized, double
      blind, placebo-controlled trials.
AB  - : Neuroinflammation has been implicated in the neurobiological pathways of
      schizophrenia. This meta-analysis evaluated the efficacy and tolerability of
      adjunctive celecoxib as a noncompetitive anti-inflammation drug in treating
      schizophrenia. Data were searched, extracted, checked and entered into the RevMan
      (version 5.3) software by two independent investigators. Standardized/weighted
      mean differences (SMDs/WMDs), risk ratio (RR) and their 95% confidence intervals
      (CIs) were calculated, as appropriate. Included were 8 randomized controlled
      trials (RCTs) with a total of 626 patients with schizophrenia including 316
      (50.5%) treated on celecoxib (400 mg/day) and 310 (49.5%) on placebo over 8.3 +/-
      2.3 weeks of treatment. Adjunctive celecoxib outperformed placebo with respect to
      total psychopathology [3 RCTs, n = 180; SMD: -0.47; 95%CI: -0.81, -0.14; P =
      0.005; I2 = 18%; 'moderate quality'], symptoms positive [3 RCTs, n = 180; SMD: 
      0.50; 95%CI: -0.79, -0.20; P = 0.001; I2 = 0%; 'moderate quality'], negative
      symptoms [3 RCTs, n = 180; SMD: -0.32; 95%CI: -0.66, 0.02; P = 0.06; I2 = 22%;
      'moderate quality'], and general psychopathology scores [3 RCTs, n = 180; SMD: 
      0.35; 95%CI: -0.65, -0.06; P = 0.02; I2 = 0%; 'moderate quality'] in first
      episode, but not chronic patients. Additionally, superiority of celecoxib for the
      Positive and Negative Syndrome Scale (PANSS) total scores was moderated by higher
      PANSS positive scores and lower PANSS negative scores at baseline. All-cause
      discontinuation [RR: 1.02; (95%CI: 0.56, 1.86); P = 0.94; I2 = 0%] and adverse
      drug reactions were similar between the two groups. Adjunctive celecoxib appears
      to be an efficacious and safe treatment in improving psychotic symptoms,
      particularly in first-episode schizophrenia. REVIEW REGISTRATION: CRD42016054233
      (http://www.crd.york.ac.uk/prospero/).

PMID- 28445799
TI  - Hysteroscopic polypectomy prior to infertility treatment: A cost analysis and
      systematic review.
AB  - The cost of fertility treatment is expensive and interventions that reduce cost
      can lead to greater efficiency and fewer embryos transferred. Endometrial polyps
      contribute to infertility and are frequently removed prior to infertility
      treatment. It is unclear whether polypectomy reduces fertility treatment cost and
      if so, the magnitude of cost reduction afforded by the procedure. The aim of this
      study was to determine whether performing office or operative hysteroscopic
      polypectomy prior to infertility treatment would be cost-effective. PubMed,
      Embase, and Cochrane libraries were used to identify publications reporting
      pregnancy rates after hysteroscopic polypectomy. Studies were required to have a
      polypectomy treatment group and control group of patients with polyps that were
      not resected. The charges of infertility treatments and polypectomy were obtained
      through infertility organizations and a private healthcare cost reporting
      website. These charges were applied to a decision tree model over the range of
      pregnancy rates observed in the representative studies to calculate an average
      cost per clinical or ongoing pregnancy. A sensitivity analysis was conducted to
      assess cost savings of polypectomy over a range of pregnancy rates and
      polypectomy costs. Pre-treatment office or operative hysteroscopic polypectomy
      ultimately saved ?6658 ($7480) and ?728 ($818), respectively, of the average cost
      per clinical pregnancy in women treated with four cycles of intrauterine
      insemination. Polypectomy prior to intrauterine insemination was cost-effective
      for clinical pregnancy rates greater than 30.2% for office polypectomy and 52.6%
      for operative polypectomy and for polypectomy price <?4414 ($4959). Office
      polypectomy or operative polypectomy saved ?15,854 ($17,813) and ?6644 ($7465),
      respectively, from the average cost per ongoing pregnancy for in vitro
      fertilization/intracytoplasmic sperm injection treated women and was cost
      effective for ongoing pregnancy rates greater than 26.4% (office polypectomy) and
      31.7% (operative polypectomy) and polypectomy price <?6376 ($7164). These
      findings suggested that office or operative hysteroscopic polypectomy was cost
      effective when performed prior to both intrauterine insemination and in vitro
      fertilization over a range of plausible pregnancy rates and procedural costs.

PMID- 28445801
TI  - An AHP-based evaluation method for teacher training workshop on information and
      communication technology.
AB  - The emergence of information and communication technology (ICT) has created
      opportunities for enhancing the learning process at different educational levels.
      However, its potential benefits can only be fully realized if teachers are
      properly trained to utilize such tools. The rapid evolution of ICT also
      necessitates rigorous assessment of training programs by participants. Thus, this
      study proposes an evaluation framework based on the Analytic Hierarchy Process
      (AHP) to systematically evaluate such workshops designed for teachers. The
      evaluation model is decomposed hierarchically into four main criteria namely: (1)
      workshop design, (2) quality of content of the workshop, (3) quality of delivery
      of the content of the workshop, and the (4) relevance of the workshop. These
      criteria are further disaggregated into 24 sub-indicators to measure the
      effectiveness of the workshop as perceived by the participants based on their own
      expectations. This framework is applied to a case study of ICT workshops done in
      the Philippines. In this case, relevance of the workshop is found to be the most
      important main criterion identified by the participants, particularly on the new
      ICT knowledge that promotes teachers' professional growth and development. The
      workshop evaluation index (WEI) is also proposed as a metric to support decision
      making by providing a mechanism for benchmarking performance, tracking
      improvement over time, and developing strategies for the design and improvement
      of training programs or workshops on ICT for teachers.

PMID- 28445802
TI  - NMNAT: It's an NAD+ synthase... It's a chaperone... It's a neuroprotector.
AB  - Nicotinamide mononucleotide adenylyl transferases (NMNATs) are a family of highly
      conserved proteins indispensable for cellular homeostasis. NMNATs are classically
      known for their enzymatic function of catalyzing NAD+ synthesis, but also have
      gained a reputation as essential neuronal maintenance factors. NMNAT deficiency
      has been associated with various human diseases with pronounced consequences on
      neural tissues, underscoring the importance of the neuronal maintenance and
      protective roles of these proteins. New mechanistic studies have challenged the
      role of NMNAT-catalyzed NAD+ production in delaying Wallerian degeneration and
      have specified new mechanisms of NMNAT's chaperone function critical for neuronal
      health. Progress in understanding the regulation of NMNAT has uncovered a
      neuronal stress response with great therapeutic promise for treating various
      neurodegenerative conditions.

PMID- 28445804
TI  - Nanoencapsulation of individual mammalian cells with cytoprotective polymer
      shell.
AB  - Nanoencapsulation of individual mammalian cells has great potential in
      biomedical, biotechnological and bioelectronic applications. However, existing
      techniques for cell nanoencapsulation generally yield short sustaining period and
      loose structure of encapsulation shell, which fails to meet the long-term
      cytoprotection and immunosuppression requirements. Here, we report a mild method
      to realize the nanoencapsulation of individual mammalian cells by layer-by-layer
      (LbL) assembly of gelatin inner layer and cross-linking of poly(ethylene glycol)
      (PEG) outer layer through thiol-click chemistry. With the present method, the
      encapsulated individual HeLa cells showed a high viability, long persistence
      period and effective resistance against macro external entities and high physical
      stress. Moreover, on-demand cell release could also be achieved by selective
      cleavage of succinimide thioether linkage in the outer PEG layer. The approach
      presented here may provide a new and versatile method for the cleavable
      nanoencapsulation of individual mammalian cells.

PMID- 28445803
TI  - JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve
      replacement.
AB  - Tissue engineered scaffolds have emerged as a promising solution for heart valve
      replacement because of their potential for regeneration. However, traditional
      heart valve tissue engineering has relied on resource-intensive, cell-based
      manufacturing, which increases cost and hinders clinical translation. To overcome
      these limitations, in situ tissue engineering approaches aim to develop scaffold
      materials and manufacturing processes that elicit endogenous tissue remodeling
      and repair. Yet despite recent advances in synthetic materials manufacturing,
      there remains a lack of cell-free, automated approaches for rapidly producing
      biomimetic heart valve scaffolds. Here, we designed a jet spinning process for
      the rapid and automated fabrication of fibrous heart valve scaffolds. The
      composition, multiscale architecture, and mechanical properties of the scaffolds
      were tailored to mimic that of the native leaflet fibrosa and assembled into
      three dimensional, semilunar valve structures. We demonstrated controlled
      modulation of these scaffold parameters and show initial biocompatibility and
      functionality in vitro. Valves were minimally-invasively deployed via transapical
      access to the pulmonary valve position in an ovine model and shown to be
      functional for 15 h.

PMID- 28445805
TI  - FAK phosphorylation plays a central role in thrombin-induced RPE cell migration.
AB  - The migration of retinal pigment epithelial (RPE) cells is an important step in
      various pathologic conditions including subretinal neovascularization (SRN),
      proliferative vitreoretinopathy (PVR) and, importantly, as a consequence of
      retinal surgery. Therefore, the elucidation of the mechanisms underlying RPE
      trans-differentiation and migration is essential for devising effective
      treatments aimed to the prevention of these disorders. A common event in these
      pathologies is the alteration of the blood-retina barrier (BRB), which allows the
      interaction of RPE cells with thrombin, a pro-inflammatory protease contained in
      serum. Our previous work has demonstrated that thrombin induces RPE cell
      cytoskeletal remodeling and migration, hallmark processes in the development of
      PVR; however, the molecular mechanisms involved are still unclear. Cell migration
      requires the disassembly of focal adhesions induced by Focal Adhesion Kinase
      (FAK) phosphorylation, together with the formation of actin stress fibers. The
      aim of the present work was to identify thrombin-activated signaling pathways
      leading to FAK phosphorylation and to determine FAK participation in thrombin
      induced RPE cell migration. Results demonstrate that the activation of PAR1 by
      thrombin induces FAK autophosphorylation at Y397 and the subsequent
      phosphorylation of Y576/577 within the activation loop. FAK phosphorylation was
      shown to be under the control of c/nPKC and PI3K/PKC-zeta, as well as by
      Rho/ROCK, since the inhibition of these pathways prevented thrombin-induced FAK
      phosphorylation and the consequent disassembly of focal adhesions, in parallel to
      FAK-dependent actin stress fiber formation and RPE cell migration. These findings
      demonstrate, for the first time, that thrombin stimulation of RPE cell
      transformation and migration are regulated by FAK tyrosine phosphorylation. Thus,
      targeting FAK phosphorylation may provide a strategical basis for PVR treatment.

PMID- 28445806
TI  - Patient engagement at the margins: Health care providers' assessments of
      engagement and the structural determinants of health in the safety-net.
AB  - Increasing "patient engagement" has become a priority for health care
      organizations and policy-makers seeking to reduce cost and improve the quality of
      care. While concepts of patient engagement have proliferated rapidly across
      health care settings, little is known about how health care providers make use of
      these concepts in clinical practice. This paper uses 20 months of ethnographic
      and interview research carried out from 2015 to 2016 to explore how health care
      providers working at two public, urban, safety-net hospitals in the United States
      define, discuss, and assess patient engagement. We investigate how health care
      providers describe engagement for high cost patients-the "super-utilizers" of the
      health care system-who often face complex challenges related to socioeconomic
      marginalization including poverty, housing insecurity, exposure to violence and
      trauma, cognitive and mental health issues, and substance use. The health care
      providers in our study faced institutional pressure to assess patient engagement
      and to direct care towards engaged patients. However, providers considered such
      assessments to be highly challenging and oftentimes inaccurate, particularly
      because they understood low patient engagement to be the result of difficult
      socioeconomic conditions. Providers tried to navigate the demand to assess
      patient engagement in care by looking for explicit positive and negative
      indicators of engagement, while also being sensitive to more subtle and intuitive
      signs of engagement for marginalized patients.

PMID- 28445807
TI  - Rewiring brain circuits to block cataplexy in murine models of narcolepsy.
AB  - Narcolepsy was first identified almost 130 years ago, but it was only 15 years
      ago that it was identified as a neurodegenerative disease linked to a loss of
      orexin neurons in the brain. It is unclear what causes the orexin neurons to die,
      but our strategy has been to place the gene for orexin into surrogate neurons in
      the validated mouse models of narcolepsy, and test whether it can block
      narcolepsy symptoms, such as cataplexy. In both the orexin knockout and the
      orexin-ataxin-3 mouse models of narcolepsy we have found that cataplexy can be
      blocked if the surrogate neurons are part of the circuit responsible for
      cataplexy. We have also determined that the orexin gene can be inserted into
      surrogate neurons in the amygdala to block emotion-induced cataplexy. Through the
      use of optogenetics we anticipate that it will be possible to preemptively block
      cataplexy.

PMID- 28445808
TI  - Treatment results in children with myeloid leukemia of Down syndrome in Saudi
      Arabia: A multicenter SAPHOS leukemia group study.
AB  - Despite the high incidence of Down syndrome (DS) in Arab countires, the incidence
      and outcomes of myeloid leukemia of DS (ML-DS) have not been studied. We
      evaluated 206 pediatric acute myeloid leukemia (AML) patients diagnosed between
      2005 and 2012 and identified 31 (15%) ML-DS. The incidence of ML-DS was 48 per
      100,000 compared to 0.6 per 100,000 for AML in non-DS children. Thus, patients
      with DS had 80-fold increased risk of ML-DS compared to AML in non-DS children.
      The median age at diagnosis was 1.8 years, male/female ratio was 1.2, majority
      (84%) of patients had FAB-M7 subtype, and the cytogenetic abnormalities were
      normal karyotype (constitutional trisomy 21) in 48%, additional trisomy in 23%,
      and other aberrations in 29%. Complete remission, cumulative incidences of
      relapse (CIR), toxic-death, and 5-year event-free survival (EFS) rates were
      96.8%, 19.4%, 13.1%, and 67.7+/-8.4%; respectively. In the present study,
      multivariate analysis revealed favorable outcome (5-year EFS 86.7+/-8.8%) for
      patients with normal karyotype. The incidence and clinical characteristics of ML
      DS in Saudi patients were comparable to other reports. However, there is a need
      to optimize risk stratification and treatment intensity to reduce CIR and toxic
      death rates to further improve outcomes of patients with ML-DS.

PMID- 28445809
TI  - Inhibition of 14q32 microRNA miR-495 reduces lesion formation, intimal
      hyperplasia and plasma cholesterol levels in experimental restenosis.
AB  - BACKGROUND AND AIMS: We aimed at investigating the role of 14q32 microRNAs in
      intimal hyperplasia and accelerated atherosclerosis; two major contributors to
      restenosis. Restenosis occurs regularly in patients treated for coronary artery
      disease and peripheral arterial disease. We have previously shown that inhibition
      of 14q32 microRNAs leads to increased post-ischemic neovascularization, and
      microRNA miR-494 also decreased atherosclerosis, while increasing plaque
      stability. We hypothesized that 14q32 microRNA inhibition has beneficial effects
      on intimal hyperplasia, as well as accelerated atherosclerosis. METHODS: Non
      constrictive cuffs were placed around both femoral arteries of C57BL/6J mice to
      induce intimal hyperplasia. Accelerated atherosclerotic plaque formation was
      induced in hypercholesterolemic ApoE-/- mice by placing semi-constrictive collars
      around both carotid arteries. 14q32 microRNAs miR-329, miR-494 and miR-495 were
      inhibited in vivo using Gene Silencing Oligonucleotides (GSOs). RESULTS: GSO-495
      administration led to a 32% reduction of intimal hyperplasia. Moreover, the
      number of macrophages in the arterial wall of mice treated with GSO-495 was
      reduced by 55%. Inhibition of miR-329 and miR-494 had less profound effects on
      intimal hyperplasia. GSO-495 administration also decreased atherosclerotic plaque
      formation by 52% and plaques of GSO-495 treated animals showed a more stable
      phenotype. Finally, cholesterol levels were also decreased in GSO-495 treated
      animals, via reduction of the VLDL-fraction. CONCLUSIONS: GSO-495 administration
      decreased our primary outcomes, namely intimal hyperplasia, and accelerated
      atherosclerosis. GSO-495 administration also favourably affected multiple
      secondary outcomes, including macrophage influx, plaque stability and total
      plasma cholesterol levels. We conclude that 14q32 microRNA miR-495 is a promising
      target for prevention of restenosis.

PMID- 28445810
TI  - Circulating cadmium concentration and risk of aortic aneurysms: A nested case
      control study within the Malmo Diet and Cancer cohort.
AB  - BACKGROUND AND AIMS: Diet and smoking expose the general population to cadmium
      (Cd), which is a toxic metal that accumulates in the arterial wall. In
      experimental studies, Cd causes reductions in proliferation of smooth muscle
      cells and cellular synthesis of procollagen. The aim of this study was to examine
      whether blood Cd levels, a valid measure of Cd exposure, are associated with
      increased risk of abdominal aortic aneurysm (AAA). METHODS: All middle-aged men
      and women enrolled in the Malmo Diet and Cancer study (n = 30 447) were followed
      from the baseline examination in 1991-1996 through 2009. A total of 297 cases
      with AAA and two randomly selected control subjects for each case, matched for
      age and sex, were included. Blood Cd was analysed by inductively coupled plasma
      mass spectrometry. Diagnoses of AAA, thoracic aortic aneurysm and aortic
      dissection were obtained from registers. RESULTS: Increased blood Cd was
      associated with increased risk of incident AAA after adjustment for smoking and
      other established risk factors for AAA. The highest tertile of blood Cd
      concentrations had a rate ratio of 2.5 (95% confidence interval 1.3, 5.0) for
      incident AAA. Concentration of blood Cd (log transformed) was not associated with
      AAA in never-smokers (n = 24). CONCLUSIONS: Blood Cd levels corresponding to the
      upper tertile of the distribution in the age- and sex-matched control group were
      associated with a 2.5-fold increase in rate ratio for incident AAA. This
      relationship was not found in the small group of never-smokers.

PMID- 28445811
TI  - Liraglutide, a GLP-1 receptor agonist, inhibits vascular smooth muscle cell
      proliferation by enhancing AMP-activated protein kinase and cell cycle
      regulation, and delays atherosclerosis in ApoE deficient mice.
AB  - BACKGROUND AND AIMS: Several studies have demonstrated that both native glucagon
      like peptide-1 (GLP-1) and GLP-1 receptor agonists suppress the progression of
      atherosclerosis in animal models. METHODS: We investigated whether liraglutide, a
      GLP-1 analogue, could prevent the development of atherosclerosis in
      apolipoprotein E knockout mice (ApoE-/-) on a high-fat diet. We also examined the
      influence of liraglutide on angiotensin II-induced proliferation of rat vascular
      smooth muscle cells (VSMCs) via enhancement of AMP-activated protein kinase
      (AMPK) signaling and regulation of cell cycle progression. RESULTS: Treatment of
      ApoE-/- mice with liraglutide (400 MUg/day for 4 weeks) suppressed
      atherosclerotic lesions and increased AMPK phosphorylation in the aortic wall.
      Liraglutide also improved the endothelial function of thoracic aortas harvested
      from ApoE-/- mice in an ex vivo study. Furthermore, liraglutide increased AMPK
      phosphorylation in rat VSMCs, while liraglutide-induced activation of AMPK was
      abolished by exendin 9-39, a GLP-1 antagonist. Moreover, angiotensin (Ang) II
      induced proliferation of VSMCs was suppressed by liraglutide in a dose-dependent
      manner, and flow cytometry of Ang II-stimulated VSMCs showed that liraglutide
      reduced the percentage of cells in G2/M phase (by arrest in G0/G1 phase).
      CONCLUSIONS: These findings suggest that liraglutide may inhibit Ang II-induced
      VSMC proliferation by activating AMPK signaling and inducing cell cycle arrest,
      thus delaying the progression of atherosclerosis independently of its glucose
      lowering effect.

PMID- 28445812
TI  - Portable aptamer biosensor of platelet-derived growth factor-BB using a personal
      glucose meter with triply amplified.
AB  - Sensitive and rapid detection of platelet-derived growth factor BB (PDGF-BB), a
      cancer-related protein, could help early diagnosis, treatment, and prognosis of
      cancers. Although some methods have been developed to detect PDGF-BB, few can
      provide quantitative results using an affordable and portable device that is
      suitable for home use or field application. In this work, we report the first use
      of a portable kind of personal glucose meter (PGM) combining a catalytic and
      molecular beacon (CAMB) system with a cation exchange reaction (CX reaction) for
      ultrasensitive PDGF-BB assay. It realized the amplification of the detection in
      three ways, including greater aptamer payload on nanoparticles, CX reaction
      releasing thousands of Zn2+ and the cycle by the catalyzing cleavage of 8-17
      DNAzyme. In the process, with the addition of PDGF-BB into the aptasensor, the
      specific recognition between aptamer and protein was initiated resulting in the
      combination of ZnS NNC for further CX reaction to release thousands of Zn2+,
      which could cleave the substrate DNA in the CAMB system realizing multiple cycle.
      The cleaved DNA fragment was designed with invertase-labeled could convert
      sucrose into glucose which could be detected and quantified by PGM accompanying
      with the change of color of the control window from yellow to green. The enhanced
      signal of the PGM has a relationship with the concentration of PDGF-BB in the
      range of 3.16*10-16M to 3.16*10-12M, and the detection limit is 0.11fM. Moreover,
      the catalytic and cleavage activities of 8-17 DNAzyme can be achieved in
      solution; thus, no enzyme immobilization is needed for detection. The triply
      amplified strategy showed high selectivity, stability, and applicability for
      detecting the desired protein.

PMID- 28445814
TI  - Comprehensive profiling and characterization of coumarins from roots, stems,
      leaves, branches, and seeds of Chimonanthus nitensOliv. using ultra-performance
      liquid chromatography/quadrupole-time-of-flight mass spectrometry combined with
      modified mass defect filter.
AB  - Chimonanthus nitensOliv. (CNO), having been studied and developed as the tea
      beverages, tea raw materials and preparations, an unique species in China, have
      been extensively used for treating colds and influenza for centuries. In the
      present study, a method based on the modified mass defect filter (MDF) was
      firstly developed and validated for comprehensive profiling of coumarins in the
      different parts of CNO via ultra-performance liquid chromatography tandem
      quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The five-point
      screening approach based on MDF and the visual isotopic ion technique could
      rapidly screen the interested precursor ions. The fragmentation behavior of
      coumarins was systematically investigated and a total of 42 coumarins including
      27 potential new ones were unambiguously or tentatively identified in the CNO.
      Collectively, the results obtained in the present work may provide useful
      information for future utilization of CNO.

PMID- 28445813
TI  - Microfluidic-integrated patterned ITO immunosensor for rapid detection of
      prostate-specific membrane antigen biomarker in prostate cancer.
AB  - An optically transparent patterned indium tin oxide (ITO) three-electrode sensor
      integrated with a microfluidic channel was designed for label-free immunosensing
      of prostate-specific membrane antigen (PSMA), a prostate cancer (PCa) biomarker,
      expressed on prostate tissue and circulating tumor cells but also found in serum.
      The sensor relies on cysteamine capped gold nanoparticles (N-AuNPs) covalently
      linked with anti-PSMA antibody (Ab) for target specificity. A
      polydimethylsiloxane (PDMS) microfluidic channel is used to efficiently and
      reproducibly introduce sample containing soluble proteins/cells to the sensor.
      The PSMA is detected and quantified by measuring the change in differential pulse
      voltammetry signal of a redox probe ([Fe(CN)6]3-/[Fe(CN)6]4-) that is altered
      upon binding of PSMA with PSMA-Ab immobilized on N-AuNPs/ITO. Detection of PSMA
      expressing cells and soluble PSMA was tested. The limit of detection (LOD) of the
      sensor for PSMA-based PCa cells is 6/40uL (i.e., 150 cells/mL) (n=3) with a
      linear range of 15-400 cells/40uL (i.e., 375-10,000 cells/mL), and for the
      soluble PSMA is 0.499ng/40uL (i.e., 12.5ng/mL) (n=3) with the linear range of
      0.75-250ng/40uL (i.e., 19-6250ng/mL), both with an incubation time of 10min. The
      results indicate that the sensor has a suitable sensitivity and dynamic range for
      routine detection of PCa circulating tumor cells and can be adapted to detect
      other biomarkers/cancer cells.

PMID- 28445815
TI  - LC-MS/MS determination of tranexamic acid in human plasma after phospholipid
      clean-up.
AB  - Tranexamic acid is a widely used antifibrinolytic drug but its pharmacology and
      pharmacokinetics remains poorly understood. Owing to the recent knowledge on
      phospholipid-induced matrix effects during human plasma analysis, our aim was to
      develop a liquid chromatography-mass spectrometry method for the quantitation of
      tranexamic acid after efficient sample clean-up. Sample preparation consisted in
      phospholipid removal and protein precipitation. Hydrophilic interaction liquid
      chromatography was used and the detection was achieved with multiple reaction
      monitoring. The method was validated according to the European Medicine Agency
      guideline in the range 1.0-1000.0MUg/mL. The performance of the method was
      excellent with a precision in the range 1.2-3.0%, an accuracy between 88.4 and
      96.6% and a coefficient of variation of the internal standard-normalized matrix
      factor below 6.7%. This method is suitable for the quantification of tranexamic
      acid in the wide range of concentrations observed during clinical studies, with
      all the advantages related to phospholipid removal.

PMID- 28445816
TI  - Disinfection byproduct formation in drinking water sources: A case study of
      Yuqiao reservoir.
AB  - This study investigated the potential formation of disinfection byproducts (DBPs)
      during chlorination and chloramination of 20 water samples collected from
      different points of Yuqiao reservoir in Tianjin, China. The concentrations of
      dissolved organic matter and ammonia decreased downstream the reservoir, while
      the specific UV absorbance (SUVA: the ratio of UV254 to dissolved organic carbon)
      increased [from 0.67 L/(mg*m) upstream to 3.58 L/(mg*m) downstream]. The raw
      water quality played an important role in the formation of DBPs. During
      chlorination, haloacetic acids (HAAs) were the major DBPs formed in most of the
      water samples, followed by trihalomethanes (THMs). CHCl3 and CHCl2Br were the
      major THM species, while trichloroacetic acid (TCAA) and dichloroacetic acid
      (DCAA) were the major HAA species. Chloramination, on the other hand, generally
      resulted in lower concentrations of THMs (CHCl3), HAAs (TCAA and DCAA), and
      haloacetonitriles (HANs). All the species of DBPs formed had positive
      correlations with the SUVA values, and HANs had the highest one (R2 = 0.8). The
      correlation coefficients between the analogous DBP yields and the SUVA values in
      chlorinated samples were close to those in chloraminated samples.

PMID- 28445818
TI  - Weighted partial least squares based on the error and variance of the recovery
      rate in calibration set.
AB  - The quantitative analysis is very difficult for the emission-excitation
      fluorescence spectroscopy of multi-component mixtures whose fluorescence peaks
      are serious overlapping. As an effective method for the quantitative analysis,
      partial least squares can extract the latent variables from both the independent
      variables and the dependent variables, so it can model for multiple correlations
      between variables. However, there are some factors that usually affect the
      prediction results of partial least squares, such as the noise, the distribution
      and amount of the samples in calibration set etc. This work focuses on the
      problems in the calibration set that are mentioned above. Firstly, the outliers
      in the calibration set are removed by leave-one-out cross-validation. Then,
      according to two different prediction requirements, the EWPLS method and the
      VWPLS method are proposed. The independent variables and dependent variables are
      weighted in the EWPLS method by the maximum error of the recovery rate and
      weighted in the VWPLS method by the maximum variance of the recovery rate. Three
      organic matters with serious overlapping excitation-emission fluorescence
      spectroscopy are selected for the experiments. The step adjustment parameter, the
      iteration number and the sample amount in the calibration set are discussed. The
      results show the EWPLS method and the VWPLS method are superior to the PLS method
      especially for the case of small samples in the calibration set.

PMID- 28445817
TI  - Nanostructural and mechanical property changes to spider silk as a consequence of
      insecticide exposure.
AB  - Neonicotinoids are one of the world's most extensively used insecticides, but
      their sub-lethal influences on non-target and beneficial organisms are not well
      known. Here we exposed the orb web spider Parawixia audax, which is found on
      arable lands in Uruguay, to a sub-lethal concentration of the broad spectrum
      insecticide Geonex (thiamethoxam + lambda-cyhalothrin) and monitored their web
      building. We collected their major ampullate silk and subjected it to tensile
      tests, wide-angle X-ray diffraction (WAXS) analysis, and amino acid composition
      analysis. Around half of the exposed spiders failed to build webs. Those that
      built webs produced irregular webs lacking spiral threads. The mechanical
      properties, nanostructures, and amino acid compositions of the silk were all
      significantly affected when the spiders were exposed to insecticides. We found
      that silk proline, glutamine, alanine and glycine compositions differed between
      treatments, indicating that insecticide exposure induced downregulation of the
      silk protein MaSp2. The spiders in the control group had stronger, tougher and
      more extensible silks than those in the insecticide exposed group. Our WAXS
      analyses showed the amorphous region nanostructures became misaligned in
      insecticide exposed silks, explaining their greater stiffness. While the
      insecticide dose we subjected P. audax to was evidently sub-lethal, the changes
      in silk physicochemical properties and the impairment to web building will
      indelibly affect their ability to catch prey.

PMID- 28445819
TI  - Structural and spectroscopic properties of complexes formed between HNCS and SO2
      in low temperature matrices.
AB  - Matrix isolation FTIR spectroscopy has been combined with quantum chemical
      calculations in the aim to characterize complexes of isothiocyanic acid HNCS with
      SO2. The geometries of the 1:1, 1:2 and 2:1 complexes were optimized at the MP2
      and DFT (B3LYPD3) levels of theory with the 6-311++G(3df,3pd) basis set. Five
      different HNCS?SO2 structures of the 1:1 stoichiometry were optimized. Three of
      them involve a weak NH?O hydrogen bond whereas two other geometries are
      stabilized by van der Waals interactions of various types. The HNCS/SO2/Ar
      spectra analysis evidences that at least one of the three hydrogen bonded
      structure is present after deposition of the matrices whereas the most stable van
      der Waals HNCS?SO2 structure as well as complexes of the 1:2 stoichiometry were
      detected upon annealing.

PMID- 28445820
TI  - The synthesis and properties of linear A-pi-D-pi-A type organic small molecule
      containing diketopyrrolopyrrole terminal units.
AB  - A novel linear A-pi-D-pi-A-type organic small molecule Ph2(PDPP)2 consisting
      diketopyrrolopyrrole (DPP) as acceptor unit, biphenylene as donor unit and
      acetylene unit as pi-linkage has been successfully designed and synthesized. Its
      corresponding thermal, photophysical and electrochemical properties as well as
      the photoinduced charge-separation process were investigated. Ph2(PDPP)2 exhibits
      high thermal stability and it can be soluble in common organic solvents such as
      chloroform and tetrahydrofuran. The photophysical properties show that DPP2Ph2
      harvests sunlight over the entire visible spectrum range in the thin-film state
      (300-800nm). DPP2Ph2 has lower band gaps and appropriate energy levels to satisfy
      the requirement of solution-processable organic solar cells. The efficient
      photoinduced charge separation process was clearly observed between DPP2Ph2 with
      PC61BM and the Ksv value was found to be as high as 2.13*104M-1. Therefore, these
      excellent properties demonstrate that the designed A-pi-D-pi-A-type small
      molecule Ph2(PDPP)2 is the prospective candidate as donor material for organic
      photovoltaic material.

PMID- 28445821
TI  - The AMPK/mTOR pathway is involved in D-dopachrome tautomerase gene transcription
      in adipocytes differentiated from SGBS cells, a human preadipocyte cell line.
AB  - In adipose tissue, D-dopachrome tautomerase (DDT), a cytokine with structural
      similarity to macrophage migration inhibitory factor, is mainly expressed in
      adipocytes rather than preadipocytes and acts as an anti-obesity adipokine in an
      autocrine manner. However, its transcriptional regulation is largely unknown. In
      order to explore molecules affecting DDT transcription, a chemical library
      screening using HEK293 cells stably expressing a DDT promoter-reporter construct
      was performed. Several derivatives of 5-aminoimidazole-4-carboxamide-1-beta-d
      ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, were
      identified as transcriptional activators of the DDT gene. Furthermore, DDT mRNA
      levels were reduced in SGBS adipocytes treated with compound C, an AMPK
      inhibitor, suggesting involvement of AMPK in DDT transcription. Overexpression of
      the FOXO1 constitutive active form reduced transcriptional activity of the DDT
      gene in SGBS cells, but increased it in HEK293 cells. Cell-type specific effects
      were also observed in the DDT gene expression of cells treated with AS1842856, a
      FOXO1 inhibitor. Finally, involvement of the mammalian target of rapamycin (mTOR)
      signaling in DDT transcription in SGBS adipocytes was investigated. Rapamycin, an
      inhibitor of mTOR, increased DDT mRNA levels and attenuated the inhibitory
      effects of compound C on DDT mRNA levels in SGBS adipocytes. In conclusion, DDT
      transcription may be regulated in a cell-dependent manner, and were enhanced by
      AMPK activation in SGBS adipocytes through inhibiting the mTOR signaling.

PMID- 28445823
TI  - Engineering metal (hydr)oxide sorbents for removal of arsenate and similar weak
      acid oxyanion contaminants: A critical review with emphasis on factors governing
      sorption processes.
AB  - To create an integrative foundation for engineering of the next generation
      inexpensive sorbent systems, this critical review addresses the existing
      knowledge gap in factor/performance relationships between weak-acid oxyanion
      contaminants and metal (hydr)oxide sorbents. In-depth understanding of
      fundamental thermodynamics and kinetics mechanisms, material fabrication, and
      analytical and characterization techniques, is necessary to engineer sorbent that
      exhibit high capacity, selectivity, stability, durability and mass transport of
      contaminants under a wide range of operating and water matrix conditions
      requirements. From the perspective of thermodynamics and kinetics, this critical
      review examines the factors affecting sorbent performances and analyzes the
      existing research to elucidate future directions aimed at developing novel
      sorbents for removal of weak-acid oxyanion contaminants from water. Only sorbents
      that allow construction of simple and inexpensive water treatment systems adapted
      to overcome fiscal and technological barriers burdening small communities could
      pave the road for providing inexpensive potable water to millions of people.
      Novel sorbents, which exhibit (1) poor performances in realistic operating and
      water matrix conditions and/or (2) do not comply with the purely driven economics
      factors of production scalability or cost expectations, are predestined to never
      be commercialized.

PMID- 28445822
TI  - Identification of the inactivating factors and mechanisms exerted on MS2
      coliphage in concentrated synthetic urine.
AB  - Volume reduction (condensation) is a key for the practical usage of human urine
      as a fertilizer because it enables the saving of storage space and the reduction
      of transportation cost. However, concentrated urine may carry infectious disease
      risks resulting from human pathogens frequently present in excreta, though the
      survival of pathogens in concentrated urine is not well understood. In this
      study, the inactivation of MS2 coliphage, a surrogate for single-stranded RNA
      human enteric viruses, in concentrated synthetic urine was investigated. The
      infectious titer reduction of MS2 coliphage in synthetic urine samples was
      measured by plaque assay, and the reduction of genome copy number was monitored
      by reverse transcription-quantitative PCR (RTqPCR). Among chemical-physical
      conditions such as pH and osmotic pressure, uncharged ammonia was shown to be the
      predominant factor responsible for MS2 inactivation, independently of urine
      concentration level. The reduction rate of the viral genome number varied among
      genome regions, but the comprehensive reduction rate of six genome regions was
      well correlated with that of the infectious titer of MS2 coliphage. This
      indicates that genome degradation is the main mechanism driving loss of
      infectivity, and that RT-qPCR targeting the six genome regions can be used as a
      culture-independent assay for monitoring infectivity loss of the coliphage in
      urine. MS2 inactivation rate constants were well predicted by a model using ion
      composition and speciation in synthetic urine samples, which suggests that MS2
      infectivity loss can be estimated solely based on the solution composition,
      temperature and pH, without explicitly accounting for effects of osmotic
      pressure.

PMID- 28445824
TI  - The shadow price of CO2 emissions in China's iron and steel industry.
AB  - As China becomes the world's largest energy consumer and CO2 emitter, there has
      been a rapidly emerging literature on estimating China's abatement cost for CO2
      using a distance function approach. However, the existing studies have mostly
      focused on the cost estimates at macro levels (provinces or industries) with few
      examining firm-level abatement costs. No work has attempted to estimate the
      abatement cost of CO2 emissions in the iron and steel industry. Although some
      have argued that the directional distance function (DDF) is more appropriate in
      the presence of bad output under regulation, the choice of directions is largely
      arbitrary. This study provides the most up-to-date estimate of the shadow price
      of CO2 using a unique dataset of China's major iron and steel enterprises in
      2014. The paper uses output quadratic DDF and investigates the impact of using
      different directional vectors representing different carbon mitigation
      strategies. The results show that the mean CO2 shadow price of China's iron and
      steel enterprises is very sensitive to the choice of direction vectors. The
      average shadow prices of CO2 are 407, 1226 and 6058Yuan/tonne respectively for
      the three different direction vectors. We also find substantial heterogeneity in
      the shadow prices of CO2 emissions among China's major iron and steel
      enterprises. Larger, listed enterprises are found to be associated lower CO2
      shadow prices than smaller, unlisted enterprises.

PMID- 28445825
TI  - Physico-chemical protection, rather than biochemical composition, governs the
      responses of soil organic carbon decomposition to nitrogen addition in a
      temperate agroecosystem.
AB  - The heterogeneous responses of soil organic carbon (SOC) decomposition in
      different soil fractions to nitrogen (N) addition remain elusive. In this study,
      turnover rates of SOC in different aggregate fractions were quantified based on
      changes in delta13C following the conversion of C3 to C4 vegetation in a
      temperate agroecosystem. The turnover of both total organic matter and specific
      organic compound classes within each aggregate fraction was inhibited by N
      addition. Moreover, the intensity of inhibition increases with decreasing
      aggregate size and increasing N addition level, but does not vary among chemical
      compound classes within each aggregate fraction. Overall, the response of SOC
      decomposition to N addition is dependent on the physico-chemical protection of
      SOC by aggregates and minerals, rather than the biochemical composition of
      organic substrates. The results of this study could help to understand the fate
      of SOC in the context of increasing N deposition.

PMID- 28445826
TI  - Exposure to fine particulate matter causes oxidative and methylated DNA damage in
      young adults: A longitudinal study.
AB  - An increased understanding is needed of the physiological effects and plausible
      biological mechanisms that link PM2.5 (particulate matter with an aerodynamic
      diameter below 2.5MUm) exposure to mortality and morbidities such as
      atherosclerosis and respiratory disease. PM2.5 causes carcinogenic health
      effects. Biomonitoring in humans has suggested that 8-oxo-7, 8-dihydro-2
      deoxyguanosine (8-oxodG) and N7-methylguanine (N7-MeG) are correlated with
      oxidative and methylated DNA damage. Thus, it is meaningful to explore the
      mechanisms of mutagenesis and carcinogenesis associated with oxidative and
      methylated DNA damage by simultaneously measuring these two markers. We recruited
      72 participants from 2 areas (residential and commercial as well as residential
      and industrial) in the greater Taipei metropolitan area at baseline. Personal
      samplers were used to collect 24-hour PM2.5-integrated samples. All participants
      completed an interview, and blood and urine samples were collected the next
      morning. All collection procedures were repeated twice after a two-month follow
      up period. Urinary 8-oxodG and N7-MeG were assayed as biomarkers of oxidative and
      methylated DNA damage, respectively. Plasma superoxide dismutase (SOD) and
      glutathione peroxidase-1 (GPX-1) were measured as biomarkers of antioxidants.
      Urinary 1-hydroxypyrene (1-OHP) was used as a biomarker of exposure to polycyclic
      aromatic hydrocarbons (PAHs). The mean PM2.5 level was 37.3MUg/m3 at baseline.
      PM2.5 concentrations were higher during winter than during spring and summer.
      After adjusting for confounds through a generalized estimating equation (GEE)
      analysis, N7-MeG was significantly increased by 8.1% (beta=0.034, 95% CIs=0.001
      0.068) per 10MUg/m3 increment in PM2.5. 8-oxodG levels were positively correlated
      with N7-MeG according to both cross-sectional and longitudinal analyses, and 1
      OHP was significantly associated with increasing 8-oxodG and N7-MeG
      concentrations. Exposure to PM2.5 increases methylated DNA damage. The mean level
      of urinary N7-MeG was 1000-fold higher than that of 8-oxodG.

PMID- 28445827
TI  - Scale effect on spatial patterns of ecosystem services and associations among
      them in semi-arid area: A case study in Ningxia Hui Autonomous Region, China.
AB  - Identifying scale effect on spatial patterns of ecosystem services and
      associations among them has been recognized as critical to the sustainable
      management of ecosystem services. We proposed a method to conveniently integrate
      ecosystem services of small scale into different larger scales. Taking Ningxia
      Hui Autonomous Region in west China as an example, we analyzed the change
      regularity of spatial patterns of 7 ecosystem services under 22 different scales.
      Further, the tradeoffs and synergies among ecosystem services across all scales
      were compared. The results showed that all of the 7 ecosystem services had been
      characterized by stable spatial cluster patterns across all of the 22 scales in
      our study. However, the extent of aggregation decreased with the increase of
      scale owing to the 'peak cutting and valley filling' process of map scale
      synthesis. Most of the associations among ecosystem services were robust across
      scales. However, there was a trend that smaller scales had more pairwise
      correlations than larger scales. The formation of tradeoffs and synergies among
      ecosystem services can be attributed to one or more of the following three
      factors: land use conflict or consistency, common drivers, and interactions among
      ecosystem services. We attribute the change of relationships among ecosystem
      services with scales to that the role of factors causing tradeoffs and synergies
      among ecosystem services may change with scales. Food supply service synergizes
      with all of the 3 regulating services at almost all of the scales in our study
      area, indicating that well managed farmlands with high net profit are beneficial
      to soil conservation and organic matter accumulation in semi-arid area.

PMID- 28445828
TI  - Targeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG
      and Stemregenin 1 improves primitive hematopoietic stem cell expansion.
AB  - Culture conditions used for the expansion of hematopoietic stem and progenitor
      cells (HSCs and HPCs, collectively HSPCs) should ideally favor the self renewal
      of long-term HSCs. At 20% O2, the synthesis of HIF-1alpha is balanced by its
      hydroxylation and proteasomal degradation. This favors HSPC differentiation, but
      can be prevented by culturing CD34+ cord blood cells in the presence of
      dimethyloxaloylglycine (DMOG). This differentiation may also be reduced by
      culturing the cells in the presence of Stemregenin 1, an antagonist of the aryl
      hydrocarbon receptor (AhR). The objective of this study was to investigate how
      hypoxia, DMOG and Stemregenin 1 might affect the expansion of HSPCs with the aim
      of identifying optimal conditions for expansion in culture. It was found that
      DMOG decreased proliferation but was effective in preserving the number of cells
      in the primitive hematopoietic sub-populations in vitro. The effect of DMOG was
      similar to hypoxia, although differences were observed with regard to the side
      population and CD34+ sub-populations. Stemregenin 1 on the other hand increased
      the size of the primitive as well as the other HSC sub-populations. The use of
      Stemregenin 1 with DMOG increased the proportion of primitive HSCs to 3.54%
      compared to 2.61% for Stemregenin 1 alone. In vivo engraftment studies confirmed
      these findings and showed that fewer cells (3710) are required for long-term
      engraftment when HSCs are grown in Stemregenin 1 together with hypoxia than in
      Stemregenin 1 under conditions of normoxia (13430).

PMID- 28445829
TI  - The role of peu-miR164 and its target PeNAC genes in response to abiotic stress
      in Populus euphratica.
AB  - Plant miR164 family is highly conserved and miR164 members regulate conserved
      targets belonging to NAC transcription factors. Our previous studies have
      revealed that peu-miR164a-e and its target gene POPTR_0007s08420 participate in
      abiotic stress response in Populus euphratica according to deep sequencing and
      degradome sequencing. In this study, miR164 family comprises six members that
      generate two mature products (miR164a-e and miR164f) and target seven NAC genes
      in P. euphratica. Co-expression in Nicotiana benthamiana and 5' RACE confirmed
      that peu-miR164 directs PeNAC070, PeNAC012 and PeNAC028 mRNAs cleavage.
      Expression profiles of primary peu-miR164 a/b/c/d/e bear similarity to those of
      peu-miR164a-e, whereas PeNAC070 and PeNAC081 showed inverse expression patterns
      with peu-miR164a-e under abiotic stresses. Existence of cis-acting elements in
      PeNAC070 promoter (ABRE,MBs, Box-W1, GC-motif, and W-box) and in peu-MIR164b
      promoter (HSE) further confirmed different responses of peu-miR164 and PeNAC070
      to abiotic stresses. Histochemical beta-glucuronidase (GUS) staining revealed
      that GUS activities increased when ProPeNAC070::GUS transgenic Arabidopsis plants
      were exposed to NaCl, mannitol and abscisic acid (ABA), whereas GUS activity of
      Propeu-MIR164b::GUS plants decreased under ABA treatment. Subcellular
      localization and transactivation assays showed that PeNAC070 protein was
      localized to the nucleus and exhibited transactivation activity at the C
      terminal. Overexpression of PeNAC070 in Arabidopsis promoted lateral root
      development, delayed stem elongation, and increased sensitivity of transgenic
      plants to drought and salt stresses. This study aids in understanding the
      adaptability of P. euphratica to extreme drought and salt environment by
      analysing tissue-specific expression patterns of miR164-regulated and specific
      promoter-regulated PeNAC genes.

PMID- 28445830
TI  - Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes
      microenvironment-mediated imatinib resistance in chronic myeloid leukemia.
AB  - Neoplasm cells from patients with chronic myeloid leukemia (CML) interact with
      stromal cells of the surrounding microenvironment. Bone marrow stromal cells
      (BMSCs) represent the main population in CML marrow stroma, which may play a key
      role in disease support and progression. Heme oxygenase-1 (HO-1) is a key enzyme
      of antioxidative metabolism that is associated with cell proliferation and
      resistance to apoptosis. We herein up-regulated HO-1 expression of BMSCs and
      evaluated whether BMSCs influenced K562 cells survival. BMSCs were isolated from
      the bone marrow of normal people and CML patients. Following co-culture of BMSCs
      and K562 cells, up-regulating HO-1 expression in bone marrow stromal cells
      increased the imatinib (IM) resistance of K562 cells, whereas the apoptosis of
      K562 cells was effectively promoted without BMSCs co-culture. The protection may
      be mediated by CXCL12 (stromal derived factors 1, SDF-1)/CXCR4 signaling. The
      CXCL12/CXCR4 interaction significantly enhanced the phosphorylation of AKT. As
      far as drug resistance was concerned, BMSCs counteracted the cytotoxic effect of
      IM administration in vitro, and they protected K562 cells from the apoptosis
      induced by kinase inhibitor IM. The regulated HO-1 expression of BMSCs provides a
      new putative target for CML therapy.

PMID- 28445831
TI  - Carotenoids in the treatment of diabetes mellitus and its complications: A
      mechanistic review.
AB  - Carotenoids are a large class of natural antioxidants that occur in many
      vegetables, foods and other natural sources. To date, a large number of
      biological properties have been reported from carotenoids, particularly
      protective effects against diabetes mellitus (DM), cancer, and neurodegenerative,
      metabolic and cardiovascular diseases. However, recent studies including clinical
      evidences, have shown that carotenoids play a role in the treatment of diabetes
      via enhancing insulin sensitivity. They are also able to protect the body from
      long-term consequences of diabetes including infectious diseases, nephropathy,
      neuronal and eye abnormalities. In this review, we try to discuss the mechanisms
      behind the biological effects of carotenoids for the prevention and treatment of
      DM and its complications. The authors believe that carotenoids will have a
      prominent place in the treatment of DM and its complications in the future.

PMID- 28445832
TI  - Study of the mechanism of protonated histidine-induced conformational changes in
      the Zika virus dimeric envelope protein using accelerated molecular dynamic
      simulations.
AB  - The Zika virus has drawn worldwide attention because of the epidemic diseases it
      causes. It is a flavivirus that has an icosahedral protein shell constituted by
      an envelope glycoprotein (E-protein) and membrane protein (M-protein) in the
      mature virion. The multistep process of membrane fusion to infect the host cell
      is pH-induced. To understand the mechanism of the conformational changes in the
      (E-M)2 protein homodimer embedded in the membrane, two 200-ns accelerated dynamic
      simulations were performed under different pH conditions. The low pH condition
      weakens the interactions and correlations in both E-protein monomers and in the E
      M heterodimer. The highly conserved residues, His249, His288, His323 and His446,
      are protonated under low pH conditions and play key roles in driving the fusion
      process. The analysis and discussion in this study may provide some insight into
      the molecular mechanism of Zika virus infection.

PMID- 28445834
TI  - Light-harvesting antenna complexes in the moss Physcomitrella patens:
      implications for the evolutionary transition from green algae to land plants.
AB  - Plants have successfully adapted to a vast range of terrestrial environments
      during their evolution. To elucidate the evolutionary transition of light
      harvesting antenna proteins from green algae to land plants, the moss
      Physcomitrella patens is ideally placed basally among land plants. Compared to
      the genomes of green algae and land plants, the P. patens genome codes for more
      diverse and redundant light-harvesting antenna proteins. It also encodes Lhcb9,
      which has characteristics not found in other light-harvesting antenna proteins.
      The unique complement of light-harvesting antenna proteins in P. patens appears
      to facilitate protein interactions that include those lost in both green algae
      and land plants with regard to stromal electron transport pathways and
      photoprotection mechanisms. This review will highlight unique characteristics of
      the P. patens light-harvesting antenna system and the resulting implications
      about the evolutionary transition during plant terrestrialization.

PMID- 28445833
TI  - Phytochrome diversification in cyanobacteria and eukaryotic algae.
AB  - Phytochromes control almost every aspect of plant biology, including germination,
      growth, development, and flowering, in response to red and far-red light. These
      photoreceptors thus hold considerable promise for engineering crop plant
      responses to light. Recently, structural research has shed new light on how
      phytochromes work. Genomic and transcriptomic studies have improved our
      understanding of phytochrome loss, retention, and diversification during
      evolution. We are also beginning to understand phytochrome function in
      cyanobacteria and eukaryotic algae.

PMID- 28445835
TI  - Economic consequences of legal and illegal drugs: The case of social costs in
      Belgium.
AB  - BACKGROUND: Legal and illegal drugs impose a considerable burden to the
      individual and to society. The misuse of addictive substances results in
      healthcare and law enforcement costs, loss of productivity and reduced quality of
      life. METHODS: A social cost study was conducted to estimate the substance
      attributable costs of alcohol, tobacco, illegal drugs and psychoactive medication
      to Belgian society in 2012. The cost-of-illness framework with prevalence-based
      and human capital approach was applied. Three cost components were considered:
      direct, indirect and intangible costs related to substance misuse. RESULTS: The
      direct and indirect cost of addictive substances was estimated at 4.6 billion
      euros in Belgium (419 euros per capita or 1.19% of the GDP) and more than 515,000
      healthy years are lost due to substance misuse. The Belgian social cost study
      reaffirms that alcohol and tobacco impose the highest cost to society compared to
      illegal drugs. Health problems are the main driver of the social cost of legal
      drugs. Law enforcement expenditure exceed the healthcare costs but only in the
      case of illegal drugs. CONCLUSION: Estimating social costs of addictive
      substances is complex because it is difficult to determine to what extent the
      societal harm is caused by substances. It can be argued that social cost studies
      take only a 'snapshot' of the monetary consequences of substance misuse.
      Nevertheless, the current study offers the most comprehensive analysis thus far
      of the social costs of substance misuse in Belgium.

PMID- 28445836
TI  - A forensic multiplex of nine novel pentameric-repeat STRs.
AB  - Pentameric-repeat short tandem repeats (STRs), consisting of loci with repeat
      units of five base-pairs, have the advantage of reduced stutter products compared
      to their tetrameric-repeat STR counterparts. This characteristic potentially
      helps the interpretation of mixed DNA profiles when minor component alleles may
      coincide with stutter peaks from the major components. To develop a simple but
      informative forensic multiplex with the capability to aid mixture interpretation,
      we designed an 11-plex assay of nine pentameric STRs new to forensic analysis
      plus two male- specific markers: DYS391 and the Y-Indel rs2032678 used in
      GlobalFilerTM (Life Technologies). East Asian-specific variation in the recently
      adopted Y-Indel rs2032678 is reported in this study for the first time in its
      forensic use as a sex marker. We estimated the levels of variation observed in
      the nine pentameric STRs in three of the major population groups sampled in the
      HGDP-CEPH human genome diversity panel: African, European and East Asian
      (combining individual populations as their sample sizes were too small for STR
      allele frequency estimations); and we include genotype data from a population
      sample of Northwest Spain. From this data, forensic informativeness metrics were
      estimated when applying the nine novel STRs in identification or kinship
      analyses. The assay was assessed for forensic sensitivity and ability to
      successfully genotype highly degraded DNA. In the profiles from the 11-plex assay
      we observed an average 2.15% stutter ratio in all the pentameric loci compared to
      7.32% across equivalently-sized tetrameric STRs in the Promega Powerplex(r) ESX
      17 kit.

PMID- 28445837
TI  - The development and validation of Huaxi emotional-distress index (HEI): A Chinese
      questionnaire for screening depression and anxiety in non-psychiatric clinical
      settings.
AB  - BACKGROUND: Depression and anxiety among general hospital patients are common and
      under-recognized in China. This study aimed toward developing a short
      questionnaire for screening depression and anxiety in non-psychiatric clinical
      settings, and to test its reliability and validity. METHODS: The item pool which
      included 35 questions about emotional distress was drafted through a
      comprehensive literature review. An expert panel review and the first clinical
      test with 288 general hospital patients were conducted for the primary item
      selection. The second clinical test was performed to select the final item in 637
      non-psychiatric patients. The reliability and validity of the final questionnaire
      were tested in 763 non-psychiatric patients, in which 211 subjects were
      interviewed by psychiatrists using Mini International Neuropsychiatric Interview
      (MINI). Multiple data analysis methods including principal components analysis
      (PCA), item response theory (IRT), and receiver operating characteristic (ROC)
      curve were used to select items and validate the final questionnaire. RESULTS:
      The series selection of items resulted in a 9-item questionnaire, namely Huaxi
      Emotional-distress Index (HEI). The Cronbach's alpha coefficient of HEI was 0.90.
      The PCA results showed a unidimensional construct. The area under the ROC curve
      (AUC) was 0.88 when compared with MINI interview. Using the optimal cut-off score
      of HEI (11/12), the sensitivity and specificity were 0.880 and 0.766,
      respectively. CONCLUSIONS: The HEI is considered as a reliable and valid
      instrument for screening depression and anxiety, which may have substantial
      clinical value to detect patients' emotional disturbances especially in the busy
      non-psychiatric clinical settings in China.

PMID- 28445838
TI  - Addition of insulin-like growth factor I to the maturation medium of bovine
      oocytes subjected to heat shock: effects on the production of reactive oxygen
      species, mitochondrial activity and oocyte competence.
AB  - This study was performed to investigate the effects of insulin-like growth factor
      I (IGF-I) addition to in vitro maturation (IVM) medium on apoptosis,
      mitochondrial membrane potential, ROS production, and developmental competence of
      bovine oocytes subjected to heat shock. Two temperatures (conventional: 24 h at
      38.5 degrees C, or heat shock: 12 h at 41 degrees C followed by 12 h at 38.5
      degrees C) and 3 IGF-I concentrations (0, 25, and 100 ng/mL) were tested during
      IVM. The oocytes were then fertilized in vitro, and the presumptive zygotes were
      cultured until reaching the blastocyst stage. There was no interaction between
      temperature and IGF-I concentration for any variable evaluated (P > 0.05). The
      addition of IGF-I did not alter the proportion of nuclear maturation, TUNEL
      positive oocytes and caspase-3 activity, or blastocyst proportion on Days 7 and 8
      post-fertilization. Furthermore, the total number of cells and the number of
      cells in the inner cell mass (ICM) in the blastocyst were not altered (P > 0.05).
      However, IGF-I increased (P < 0.05) the mitochondrial membrane potential and the
      production of ROS in oocytes and decreased (P < 0.05) the proportion of apoptotic
      cells in the ICM in blastocysts. Heat shock increased (P < 0.05) the proportion
      of TUNEL-positive oocytes and ROS production and reduced (P < 0.05) the
      mitochondrial membrane potential. Moreover, heat shock increased (P < 0.05) the
      apoptosis proportion in the ICM cells. In conclusion, supplementing IVM medium
      with IGF-I may increase the mitochondrial membrane potential and ROS production
      in oocytes and decrease apoptosis in the ICM in blastocysts. Heat shock for 12 h
      compromised oocyte developmental competence and increased apoptosis within the
      ICM cells of the blastocysts.

PMID- 28445839
TI  - Temporal lobe spikes: EEG-fMRI contributions to the "mesial vs. lateral" debate.
AB  - OBJECTIVE: It has been reported that interictal epileptic discharges (IEDs)
      recorded in temporal regions on scalp EEG are unlikely to originate from mesial
      temporal structures. However, EEG-fMRI sometimes show mesial temporal activation.
      We hypothesized that BOLD activation in the temporal neocortex is weaker than in
      the mesial structures, reflecting the fact that propagated activity has less
      metabolic demand than the original discharge. METHODS: Twelve patients with
      epilepsy who have BOLD response in mesial temporal structures were selected from
      our EEG-fMRI database. We searched the temporal lobe ipsilateral to IEDs and
      checked whether there is positive BOLD response in the neocortex. RESULTS: All
      IED types showed a BOLD response in the temporal neocortex ipsilateral to the
      mesial temporal BOLD response. T-values were higher in mesial temporal structures
      than in neocortex in 13/16 cases. CONCLUSIONS: Hemodynamic changes were observed
      in the mesial temporal lobe at the time of IEDs recorded from the temporal region
      on the scalp. The finding of smaller BOLD changes in the ipsilateral neocortex is
      in agreement with our hypothesis. SIGNIFICANCE: Our study indicates that scalp
      recorded temporal lobe spikes are likely to result from mesial temporal spikes
      propagating neuronally to the neocortex.

PMID- 28445840
TI  - Modification of cognitive biases related to posttraumatic stress: A systematic
      review and research agenda.
AB  - Cognitive models of Posttraumatic Stress Disorder (PTSD) postulate that cognitive
      biases in attention, interpretation, and memory represent key factors involved in
      the onset and maintenance of PTSD. Developments in experimental research
      demonstrate that it may be possible to manipulate such biases by means of
      Cognitive Bias Modification (CBM). In the present paper, we summarize studies
      assessing cognitive biases in posttraumatic stress to serve as a theoretical and
      methodological background. However, our main aim was to provide an overview of
      the scientific literature on CBM in (analogue) posttraumatic stress. Results of
      our systematic literature review showed that most CBM studies targeted
      attentional and interpretation biases (attention: five studies; interpretation:
      three studies), and one study modified memory biases. Overall, results showed
      that CBM can indeed modify cognitive biases and affect (analog) trauma symptoms
      in a training congruent manner. Interpretation bias procedures seemed effective
      in analog samples, and memory bias training proved preliminary success in a
      clinical PTSD sample. Studies of attention bias modification provided more mixed
      results. This heterogeneous picture may be explained by differences in the type
      of population or variations in the CBM procedure. Therefore, we sketched a
      detailed research agenda targeting the challenges for CBM in posttraumatic
      stress.

PMID- 28445841
TI  - Copper(II) and iron(III) ions inhibit respiration and increase free radical
      mediated phospholipid peroxidation in rat liver mitochondria: Effect of
      antioxidants.
AB  - Rat liver mitochondria (1.5-2.1mg protein.mL-1) supplemented with either 25 and
      100MUM Cu2+ or 100 and 500MUM Fe3+ show inhibition of active respiration (O2
      consumption in state 3) and increased phospholipid peroxidation . Liver
      mitochondria were supplemented with the antioxidants reduced glutathione, N
      acetylcysteine or butylated hydroxitoluene, to evaluate their effects on the
      above-mentioned alterations. Although the mitochondrial dysfunction is clearly
      associated to phospholipid peroxidation, the different responses to antioxidant
      supplementation indicate that the metal ions have differences in their mechanisms
      of toxicity. Mitochondrial phospholipid peroxidation through the formation of
      hydroxyl radical by a Fenton/Haber-Weiss mechanism seems to precede the
      respiratory inhibition and to be the main fact in Fe-induced mitochondrial
      dysfunction. In the case of Cu2+, it seems that the ion oxidizes glutathione, and
      low molecular weight protein thiol groups in a direct reaction, as part of its
      intracellular redox cycling. The processes involving phospholipid peroxidation,
      protein oxidation and mitochondrial respiratory inhibition characterize a redox
      dyshomeostatic situation that ultimately leads to cell death. However, Cu2+
      exposure involves an additional, yet unidentified, toxic event as previous
      reduction of the metal with N-acetylcysteine has only a minor effect in
      preventing the mitochondrial damage.

PMID- 28445842
TI  - Betaeta-eudesmol reduces stem cell factor-induced mast cell migration.
AB  - Previously, we showed the inhibitory effects of beta-eudesmol on mast cell
      mediated allergic inflammatory responses. Stem cell factor (SCF) participates in
      allergic reactions through the differentiation and migration of mast cells.
      However, the effects of beta-eudesmol on SCF-mediated allergic reactions are
      poorly understood. Herein, we showed that a treatment of rat peritoneal mast
      cells (RPMCs) with beta-eudesmol markedly suppressed SCF-induced mast cell
      migration and morphological alterations in a concentration-dependent manner. beta
      eudesmol also reduced F-actin formation. The activation of Fyn kinase, Rac1
      GTPase, and p38 mitogen-activated protein kinases as increased by SCF was reduced
      by beta-eudesmol. Moreover, beta-eudesmol significantly abolished SCF-induced
      tumor necrosis factor-alpha and intercellular adhesion molecule-1 production
      without cytotoxicity. These results demonstrate that beta-eudesmol has an anti
      allergic inflammatory effect through the inhibition of mast cell migration and
      inflammatory cytokine production.

PMID- 28445843
TI  - Health and income inequalities in Europe: What is the role of circumstances?
AB  - Equality of opportunity theories distinguish between inequalities due to
      individual effort and those due to external circumstances. Recent research has
      shown that half of the variability in income of World population was determined
      by country of birth and income distribution. Since health and income are
      generally strictly related, the aim of this paper is to estimate how much
      variability in income and health is determined by external circumstances. We use
      data from the Survey of Health, Ageing and Retirement (SHARE) and the English
      Longitudinal Survey on Ageing (ELSA), two comparable multidisciplinary surveys
      that provide micro-level data on health and financial resources among the elderly
      for a large number of European countries. Our baseline estimation shows that
      about 20% of the variability in income is explained by current country-specific
      circumstances, while health outcomes range from 12% using BMI to 19% using self
      rated health. By including early-life circumstances, the explained variability
      increases almost 20 percentage points for income and for self-rated health but
      less for other health outcomes. Finally, by controlling for endogeneity issues
      linked with effort, our estimates indicate that circumstances better explain
      variability in health outcomes. Results are robust to some tests, and the
      implications of these findings are discussed.

PMID- 28445844
TI  - Upregulation of miR-142-3p Improves Drug Sensitivity of Acute Myelogenous
      Leukemia through Reducing P-Glycoprotein and Repressing Autophagy by Targeting
      HMGB1.
AB  - miR-142-3p was reported to be downregulated in acute myelogenous leukemia (AML)
      and acted as a novel diagnostic marker. However, the regulatory effect of miR-142
      3p on drug resistance of AML cells and its underlying mechanism have not been
      elucidated. Here, we found that miR-142-3p was significantly downregulated and
      high mobility group box 1 (HMGB1) was dramatically upregulated in AML samples and
      cells, as well as drug-resistant AML cells. P-gp level and autophagy were
      markedly enhanced in HL-60/ADR and HL-60/ATRA cells. miR-142-3p overexpression
      improved drug sensitivity of AML cells by inhibiting cell viability and promoting
      apoptosis, and inhibited P-gp level and autophagy in drug-resistant AML cells,
      whereas HMGB1 overexpression obviously reversed these effect. HMGB1 was
      demonstrated to be a target of miR-142-3p, and miR-142-3p negatively regulated
      HMGB1 expression. In conclusion, our study elucidated that upregulation of miR
      142-3p improves drug sensitivity of AML through reducing P-glycoprotein and
      repressing autophagy by targeting HMGB1, contributing to better understanding the
      molecular mechanism of drug resistance in AML.

PMID- 28445845
TI  - The capacity and effectiveness of diosmectite and charcoal in trapping the
      compounds causing the most frequent intoxications in acute medicine: A
      comparative study.
AB  - The aim of the study was to compare the adsorption ability of two adsorbent
      materials, namely diosmectite and activated charcoal towards selected model
      compounds that are most commonly involved in acute intoxication. Eleven model
      compounds were selected: acetylsalicylic acid, alpha-amanitin, amlodipine,
      digoxin, phenobarbital, ibuprofen, imipramine, carbamazepine, oxazepam,
      promethazine, and theophylline. Of the tested compounds, promethazine and
      imipramine were the most effectively adsorbed to diosmectite. Their adsorption to
      diosmectite (0.356+/-0.029mg promethazine/mg diosmectite and 0.354+/-0.019mg
      imipramine/mg diosmectite, respectively) was significantly higher than their
      adsorption to activated charcoal. The effect of temperature and pH on the
      adsorption efficiencies was also evaluated. In the case of experiments with
      mixture of both adsorbents, they mostly behaved in a solution independently or in
      a slightly antagonistic way. Using various methods such as N2 adsorption and
      thermogravimetric analysis, the structure and texture of diosmectite and
      activated charcoal were attained.

PMID- 28445846
TI  - A sharp, robust, and quantitative method by liquid chromatography tandem mass
      spectrometry for the measurement of EAD for acute radiation syndrome and its
      application.
AB  - 17-Ethinyl-3,17-dihydroxyandrost-5-ene (EAD) is an agent designed for the
      treatment of acute radiation syndrome (ARS). Given its vital role played in the
      prevention and mitigation of ARS, the development of a sharp, sensitive and
      robust liquid chromatography tandem mass spectrometry (LC-MS/MS) method to
      monitor the metabolism of EAD in vivo was crucial. A new method was constructed
      and validated for the determination of EAD with the internal standard of androst
      5-ene-3beta,17beta-diol (5-AED). The blood samples were precipitated with
      methanol, centrifuged, from which the supernatant was separated on UPLC with C18
      column and eluted in gradient with acetonitrile and Milli-Q water both containing
      0.1% formic acid (FA). Quantification was performed by a triple quadrupole mass
      spectrometer with electro spray ionization (ESI) in multiple reactive monitoring
      (MRM) positive mode. A good linearity was obtained with R>0.99 for EAD within its
      calibration range from 5 to 1000ngmL-1 with a lowest limit of quantification
      (LLOQ) of 5ngmL-1. Inter- and intra-day accuracy and precision of three levels of
      quality control (QC) samples were within the range of 15%, while the LLOQ was
      within 20%. Samples were stable under the circumstances of the experiments. The
      method was simple, accurate and robust applied to determine the concentrations of
      EAD in Wistar rat after a single administration of EAD orally at the dose of
      100mgkg-1.

PMID- 28445847
TI  - To elute or not to elute in immunocapture bottom-up LC-MS.
AB  - Immunocapture-based bottom-up LC-MS is a promising technique for the
      quantification of low abundant proteins. Magnetic immunocapture beads provide
      efficient enrichment from complex samples through the highly specific interaction
      between the target protein and its antibody. In this article, we have performed
      the first thorough comparison between digestion of proteins while bound to
      antibody coated beads versus after elution from the beads. Two previously
      validated immunocapture based MS methods for the quantification of pro-gastrin
      releasing peptide (ProGRP) and human chorionic gonadotropin (hCG) were used as
      model systems. The tryptic peptide generation was shown to be protein dependent
      and influenced by protein folding and accessibility towards trypsin both on-beads
      and in the eluate. The elution of proteins bound to the beads was also shown to
      be incomplete. In addition, the on-beads digestion suffered from non-specific
      binding of the trypsin generated peptides. A combination of on-beads digestion
      and elution may be applied to improve both the quantitative (peak area of the
      signature peptides) and qualitative yield (number of missed cleavages, total
      number of identified peptides, coverage, signal intensity and number of zero
      missed cleavage peptides) of the target proteins. The quantitative yield of
      signature peptides was shown to be reproducible in all procedures tested.

PMID- 28445848
TI  - A systematic and critical review on bioanalytical method validation using the
      example of simultaneous quantitation of antidiabetic agents in blood.
AB  - A systematic and critical review was conducted on bioanalytical methods validated
      to quantify combinations of antidiabetic agents in human blood. The aim of this
      article was to verify how the validation process of bioanalytical methods is
      performed and the quality of the published records. The validation assays were
      evaluated according to international guidelines. The main problems in the
      validation process are pointed out and discussed to help researchers to choose
      methods that are truly reliable and can be successfully applied for their
      intended use. The combination of oral antidiabetic agents was chosen as these are
      some of the most studied drugs and several methods are present in the literature.
      Moreover, this article may be applied to the validation process of all
      bioanalytical.

PMID- 28445849
TI  - A reference measurement procedure for amino acids in blood using isotope dilution
      ultra-performance liquid chromatography-tandem mass spectrometry.
AB  - We described a reference measurement procedure for amino acid (AA) quantification
      in blood samples based on deproteinization with 5-sulfosalicylic acid (SSA) and
      an isotope dilution-ultra performance liquid chromatography-tandem mass
      spectrometry (LC-MS) method. The serum was deproteinized with 15% v/v SSA and the
      supernatant was injected directly into the LC-MS system without further
      processing. Compared with the use of other precipitants and water as a control,
      five model AAs-valine, isoleucine, leucine, tyrosine, and phenylalanine-in the
      SSA-treated samples showed ionization enhancement as well as stable background
      signals without significant ion suppression effects. Five analytes were clearly
      separated within 3min using gradient elution and ion-pair chromatography of water
      and acetonitrile containing 0.1% v/v trifluoroacetic acid. The limit of detection
      range of this method was 2-52fmol, and the RSDs of accuracy and precision from
      intra- and inter-day assays were within 2.7%. The method was applied to various
      blood samples including serum, whole blood and plasma, with no reasonable
      measurement bias revealed. The quantification accuracy of this method was then
      assessed using commercially available plasma certified reference material (CRM)
      for AA, and the results agreed well within certified values. We finally applied
      this method to the determination of candidate serum CRM. The optimized protocol
      was found to be suitable for the accurate quantification of five AAs in serum,
      and may satisfactorily serve as a primary method for AA measurement in various
      blood matrices.

PMID- 28445850
TI  - Simultaneous quantification of busulfan, clofarabine and F-ARA-A using isotope
      labelled standards and standard addition in plasma by LC-MS/MS for exposure
      monitoring in hematopoietic cell transplantation conditioning.
AB  - In allogeneic hematopoietic cell transplantation (HCT) it has been shown that
      over- or underexposure to conditioning agents have an impact on patient outcomes.
      Conditioning regimens combining busulfan (Bu) and fludarabine (Flu) with or
      without clofarabine (Clo) are gaining interest worldwide in HCT. To evaluate and
      possibly adjust full conditioning exposure a simultaneous analysis of Bu, F-ARA-A
      (active metabolite of Flu) and Clo in one analytical run would be of great
      interest. However, this is a chromatographical challenge due to the large
      structural differences of Bu compared to F-ARA-A and Clo. Furthermore, for the
      bioanalysis of drugs it is common to use stable isotope labelled standards
      (SILS). However, when SILS are unavailable (in case of Clo and F-ARA-A) or very
      expensive, standard addition may serve as an alternative to correct for recovery
      and matrix effects. This study describes a fast analytical method for the
      simultaneous analysing of Bu, Clo and F-ARA-A with liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) including standard addition methodology using 604
      spiked samples. First, the analytical method was validated in accordance with
      European Medicines Agency guidelines. The lower limits of quantification (LLOQ)
      were for Bu 10MUg/L and for Clo and F-ARA-A 1MUg/L, respectively. Variation
      coefficients of LLOQ were within 20% and for low medium and high controls were
      all within 15%. Comparison of Bu, Clo and F-ARA-A standard addition results
      correspond with those obtained with calibration standards in calf serum. In
      addition for Bu, results obtained by this study were compared with historical
      data analysed within TDM. In conclusion, an efficient method for the simultaneous
      quantification of Bu, Clo and F-ARA-A in plasma was developed. In addition, a
      robust and cost-effective method to correct for matrix interference by standard
      addition was established.

PMID- 28445851
TI  - Development and validation of a UHPLC-ESI-MS/MS method for the simultaneous
      quantification of mammal lysophosphatidylcholines and
      lysophosphatidylethanolamines in serum.
AB  - Recent investigations based on non-targeted metabolomics have proposed
      lysophospholipids (Lyso-PLs) as biomarkers of different diseases. In particular,
      lysophosphatidylcholines (Lyso-PCs) and lysophosphatidylethanolamines (Lyso-PEs)
      have been associated with serious lipid pathologies. Methods to determine the
      different molecular species in a biological sample and to quantify even less
      abundant species are required for the evaluation of the Lyso-PL pattern as a
      novel comprehensive biomarker of dyslipidemia. This study describes the
      development and validation of an ultra-high-performance liquid chromatography
      coupled to tandem mass spectrometry assay for the determination of a large number
      of Lyso-PCs and Lyso-PEs in biological samples. The method was validated in rat
      serum using two simple methanol-based extractions with low sample volumes (5
      50MUL) that covered the wide concentration range of these metabolites. In total,
      thirty-one Lyso-PLs were separated and quantified with low method limits of
      detection and quantification, reaching values of 0.2 and 0.8nM, respectively. The
      method was subsequently applied in the identification of Lyso-PL-related changes
      produced by the chronic intake of a cafeteria diet. The results showed
      alterations in the majority of Lyso-PCs and Lyso-PEs in rat serum. Furthermore,
      multivariate analysis indicated that the comprehensive evaluation of serum Lyso
      PLs could be an excellent indicator of the nutritional phenotype associated with
      an increased risk of lipid disorders.

PMID- 28445852
TI  - Sensitive analysis and pharmacokinetic study of epalrestat in C57BL/6J mice.
AB  - Epalrestat is clinically applied for the management of diabetic peripheral
      neuropathy, yet its pharmacokinetic properties are not well understood. In this
      study, a rapid and sensitive LC-MS/MS method was established for assaying
      epalrestat in bio-samples of mice. The method was validated and it showed a good
      linearity over the range of 2-5000ng/mL, a precision of less than 12.3%, and
      recovery and matrix effects of 112.5-123.6% and 87.9-89.5%, respectively. After
      administration of a single dose of epalrestat administered, the exposure level of
      AUC0-infinity was positively dose-dependent and the mean Cmax, AUC0-12h, T1/2,
      and MRT were 36.23+/-7.39MUg/mL, 29,086.5MUg/Lh, 1.2h and 1.8h, respectively.
      Epalrestat was highly exposed in stomach, intestine, liver and kidney, and only a
      small amount was detected in brain, urine and feces. Multi-dose of epalrestat
      significantly increased MRT and apparent volume of distribution (Vd) relative to
      those of a single-dose.

PMID- 28445853
TI  - Cannabidiol-Delta9-tetrahydrocannabinol interactions on acute pain and locomotor
      activity.
AB  - BACKGROUND: Previous studies suggest that cannabidiol (CBD) may potentiate or
      antagonize Delta9-tetrahydrocannabinol's (THC) effects. The current study
      examined sex differences in CBD modulation of THC-induced antinociception,
      hypolocomotion, and metabolism. METHODS: In Experiment 1, CBD (0, 10 or 30mg/kg)
      was administered 15min before THC (0, 1.8, 3.2, 5.6 or 10mg/kg), and rats were
      tested for antinociception and locomotion 15-360min post-THC injection. In
      Experiments 2 and 3, CBD (30mg/kg) was administered 13h or 15min before THC
      (1.8mg/kg); rats were tested for antinociception and locomotion 30-480min post
      THC injection (Experiment 2), or serum samples were taken 30-360min post-THC
      injection to examine CBD modulation of THC metabolism (Experiment 3). RESULTS: In
      Experiment 1, CBD alone produced no antinociceptive effects, while enhancing THC
      induced paw pressure but not tail withdrawal antinociception 4-6h post-THC
      injection. CBD alone increased locomotor activity at 6h post-injection, but
      enhanced THC-induced hypolocomotion 4-6h post-THC injection, at lower THC doses.
      There were no sex differences in CBD-THC interactions. In Experiments 2 and 3,
      CBD did not significantly enhance THC's effects when CBD was administered 13h or
      15min before THC; however, CBD inhibited THC metabolism, and this effect was
      greater in females than males. CONCLUSIONS: These results suggest that CBD may
      enhance THC's antinociceptive and hypolocomotive effects, primarily prolonging
      THC's duration of action; however, these effects were small and inconsistent
      across experiments. CBD inhibition of THC metabolism as well other mechanisms
      likely contribute to CBD-THC interactions on behavior.

PMID- 28445854
TI  - Balance training in individuals with Parkinson's disease: Therapist-supervised
      vs. home-based exercise programme.
AB  - BACKGROUND: Poor locomotion and balance in Parkinson's disease (PD) often
      diminishes independence. Accordingly, gait is considered one of the most relevant
      rehabilitation outcomes, and home-based balance exercises might be a viable mode
      of exercise delivery for individuals with PD. However, research on PD
      interventions rarely indicate best practices to deliver exercises. Therefore,
      this study endeavoured to compare the efficacy of a home-based and therapist
      supervised balance programme on gait parameters, dynamic balance, balance
      confidence and motivation in individuals diagnosed with PD. METHODS: An
      experimental study design, including a cluster randomized convenience sample, of
      40 participants with idiopathic PD (Hoehn and Yahr stage I-III; age: 65.0+/
      7.7years). Participants were divided into a therapist-supervised (n=24) and home
      based group (n=16). Groups received either eight weeks of balance training with
      an exercise therapist or a DVD. Outcome measures include the instrumented Timed
      Up-and-Go, Functional Gait Analysis (FGA), Activity-specific Balance confidence
      (ABC) scale and Intrinsic Motivation Inventory (IMI). RESULTS: Both groups
      improved in stride length (p<0.05). Similar FGA improved by 9% and 16% in the
      therapist-supervised and home-based group, respectively (p<0.01). Only the
      therapist-supervised group showed improvements in ABC (p=0.051), stride velocity
      (p=0.0006) and cadence (p=0.046) over the intervention; the latter two were also
      better compared to home-based (p<0.05). Furthermore the therapist-supervised
      group were more motivated (p=002). CONCLUSION: The home-based balance programme
      was effective in improving some aspects of gait, albeit the programme supervised
      by an exercise therapist included somewhat more benefits after the intervention
      i.e. stride velocity and cadence in individuals with mild to moderate PD.

PMID- 28445855
TI  - Speed dependent effects of laterally wedged insoles on gait biomechanics in
      healthy subjects.
AB  - Laterally wedged insoles have been shown to be effective for the reduction of the
      knee adduction moment and other biomechanical variables that are associated with
      the pathogenesis of knee osteoarthritis. However, inconclusive results such as
      adverse effects in individual subjects or even no group-wise wedge effects have
      been presented in different studies and it has been suggested to identify
      variables that potentially confound the wedge effect. The main objective of this
      study was the investigation of interaction effects of lateral wedges with walking
      speed, as different self-selected speeds have mainly been used in previous
      studies. Twenty-two healthy subjects completed gait analysis trials on an
      instrumented treadmill. They walked in different speed conditions (0.9, 1.1, 1.3,
      1.5m/s) with a neutral and a laterally wedged insole. Kinematics were acquired
      using infrared cinematography with reflective markers attached to the lower body.
      From the stance phase we extracted biomechanical parameters that are associated
      with knee joint loading and osteoarthritis severity. No interaction effect of
      lateral wedges and speed was observed for most biomechanical parameters except
      for the ankle eversion range of motion. The main effects of wedges were
      reductions of the external knee adduction moment and of the knee adduction
      angular impulse. All biomechanical variables changed with increasing speed. Only
      the lateral offset of the center of pressure did not respond to wedge or to speed
      changes. Our results suggest that different self-selected speeds do not confound
      the effect of laterally wedged insoles.

PMID- 28445856
TI  - Procyanidin, a kind of biological flavonoid, induces protective anti-tumor
      immunity and protects mice from lethal B16F10 challenge.
AB  - Recently, increasing evidences show that procyanidin (PC) modulate immune
      responses in human. To evaluate adjuvant effects of PC on vaccine immune
      modulation and anti-tumor activity, we formulated PC with B16F10 tumor antigen as
      tumor vaccine to immune C57BL/6 mice and used intramuscular injection before
      challenge with tumor B16F10 cells. Our results revealed that PC enhanced T cell
      mediated immune responses both in vitro and in vivo. Moreover, the B16F10 tumor
      vaccine induced some degree of anti-tumor effects as evaluated by the inhibition
      of tumor growth and the prolongation of survival. The tumor-bearing mice showed a
      high level of specific cytotoxic activity and had activated CD8 T cells that
      secreted perforin, IFN-gamma and TNF-alpha in response to the stimulation with
      antigen in vitro. Taken together, current study presents evidence that PC may be
      used as a promising vaccine adjuvant.

PMID- 28445857
TI  - Binding of resveratrol to the minor groove of DNA sequences with AATT and TTAA
      segments induces differential stability.
AB  - Interactions of a natural stilbene compound, resveratrol with two DNA sequences
      containing AATT/TTAA segments have been studied. Resveratrol is found to interact
      with both the sequences. The mode of interaction has been studied using
      absorption, steady state fluorescence and circular dichroism spectroscopic
      techniques. UV-visible absorption and fluorescence studies provided the
      information regarding the binding constants and the stoichiometry of binding,
      whereas circular dichroism studies depicted the structural changes in DNA upon
      resveratrol binding. Our results evidenced that, though resveratrol showed
      similar affinity to both the sequences, the mode of interactions was different.
      The binding constants of resveratrol to AATT/TTAA sequences were found to be
      7.55*105M-1 and 5.42*105M-1 respectively. Spectroscopic data evidenced for a
      groove binding interaction. Melting studies showed that the binding of
      resveratrol induces differential stability to the DNA sequences d(CGTTAACG)2 and
      d(CGAATTCG)2. Fluorescence data showed a stoichiometry of 1:1 for d(CGAATTCG)2
      resveratrol complex and 1:4 for d(CGTTAACG)2-resveratrol complex. Molecular
      docking studies demonstrated that resveratrol binds to the minor groove region of
      both the sequences to form stable complexes with varied atomic contacts to the
      DNA bases or backbone. Both the complexes are stabilized by hydrogen bond
      formation. Our results evidenced that modulation of DNA sequence within the same
      bases can greatly alter the binding geometry and stability of the complex upon
      binding to small molecule inhibitor compounds like resveratrol.

PMID- 28445858
TI  - The impact of minor blood transfusion on the outcome after coronary artery bypass
      grafting.
AB  - PURPOSE: To investigate the impact of minor perioperative bleeding requiring
      transfusion of 1-2 red blood cell (RBC) units on the outcome after coronary
      artery bypass grafting (CABG). METHODS: Sixteen cardiac surgical centers
      contributed to the prospective European CABG registry (E-CABG). 1014 patients
      receiving 1-2 RBC units during or after isolated CABG were compared to 2264
      patients not receiving RBCs. RESULTS: In 827 propensity score matched pairs,
      transfusion of 1-2 RBC units did not affect the risk of in-hospital/30-day death
      (p=0.523) or stroke (p=0.804). However, RBC transfusion was associated with an
      increased risk of acute kidney injury (p=0.008), sternal wound infection
      (p=0.001), postoperative use of antibiotics (p=0.001), prolonged use of inotropes
      (p<0.0001), use of intra-aortic balloon pump (p=0.012), length of intensive care
      unit stay (p<0.0001) and length of in-hospital stay (p<0.0001). Matched paired
      analysis excluding pre- and postoperative critical hemodynamic conditions showed
      that RBC transfusion was associated with an increased risk of major complications
      except in-hospital/30-day death. CONCLUSION: Minor perioperative bleeding and
      subsequent transfusion of 1-2 RBC units did not affect the risk of early death,
      but increased the risk of other major adverse events. Minimizing perioperative
      bleeding and prevention of even low-volume RBC transfusion may improve the
      outcome after CABG.

PMID- 28445859
TI  - A risk scoring model based on vital signs and laboratory data predicting transfer
      to the intensive care unit of patients admitted to gastroenterology wards.
AB  - PURPOSE: To compare the ability of a score based on vital signs and laboratory
      data with that of the modified early warning score (MEWS) to predict ICU transfer
      of patients with gastrointestinal disorders. MATERIALS AND METHODS: Consecutive
      events triggering medical emergency team activation in adult patients admitted to
      the gastroenterology wards of the Asan Medical Center were reviewed. Binary
      logistic regression was used to identify factors predicting transfer to the ICU.
      Gastrointestinal early warning score (EWS-GI) was calculated as the sum of
      simplified regression weights (SRW). RESULTS: Of the 1219 included patients, 468
      (38%) were transferred to the ICU. Multivariate analysis identified heart
      rate>=105bpm (SRW 1), respiratory rate>=26bpm (SRW 2), ACDU (Alert, Confused,
      Drowsy, Unresponsive) score>=1 (SRW 2), SpO2/FiO2 ratio<240 (SRW 2), creatinine
      >=2.0mg/dL (SRW 2), total bilirubin >=9.0mg/dL (SRW 2), prothrombin
      time/international normalized ratio (INR) >=1.5 (SRW 2), and lactate >=3.0mmol/L
      (SRW 2) for inclusion in EWS-GI. The area under the receiver operating
      characteristic curve of the EWS-GI was larger than that of MEWS (0.76 vs. 0.64;
      P<0.001). CONCLUSIONS: EWS-GI may predict ICU transfer among patients admitted to
      gastroenterology wards. The EWS-GI should be prospectively validated.

PMID- 28445860
TI  - Brephedrone: A new psychoactive substance seized in Brazil.
AB  - At the beginning of 2015, sixty-two capsules containing red-brown crystals seized
      in a historical city in Brazil were sent to this forensic laboratory for drug
      testing analysis. The material was identified as being Brephedrone, a new
      psychoactive substance and a bromine synthetic cathinone that is related to
      serotonin transportation. This substance was analyzed by ATR-FTIR, GC-MS, LC-MS,
      1H, 13C and 2D NMR. Brephedrone apprehensions have been previously reported in
      Finland, France and Spain. It was the first detection of this substance in the
      State of Minas Gerais. No reports or information regarding any other apprehension
      nor identification of Brephedrone in Brazil were known prior to the present case.

PMID- 28445861
TI  - The application of silicon sol-gel technology to forensic blood substitute
      development: Investigation of the spreading dynamics onto a paper surface.
AB  - This work investigates the spreading dynamics of three candidate sol-gel
      solutions, of ranging viscosities, surface tensions and densities, and compares
      them with water and two commercial blood substitute products. Droplets were
      created with different sizes (10 to75MUL) and impact velocities (1.4 to 6.0m/s)
      to strike 176gsm cardstock. Over 2200 droplets were created using the six
      different fluids and their final dried stain diameter was measured. Droplet
      spread was plotted using the Scheller and Bousfield correlation and uses
      effective viscosity as a parameter for non-Newtonian fluids. Comparing the
      results to an expected whole human blood range validated the spread of the
      candidate FBS sol-gel material in passive drip bloodstain pattern simulation.
      These findings complement the practical application of the material as a safe
      substitute for demonstrating droplet spread under controlled conditions on hard
      paper surfaces.

PMID- 28445869
TI  - Silicone Oil-Related Visual Loss.
AB  - BACKGROUND: Silicone oil (SO) is used as an intravitreal tamponade agent in
      vitreoretinal surgery for rhegmatogenous retinal detachment (RRD) complicated by
      proliferative vitreoretinopathy or with large, multiple retinal tears. Usually,
      SO is left in the eye for at least 3 months. Although its use can lead to well
      known complications, intraocular SO is generally well tolerated. Some studies
      have reported unexpected central vision loss after SO use or removal. OBJECTIVE:
      To investigate and analyze the reason for visual loss after the use or removal of
      intraocular SO in patients who underwent vitrectomy surgeries for RRD. PATIENTS
      AND METHODS: A retrospective observational case series of 12 patients with macula
      on RRD who reported visual loss after the use or removal of SO was reviewed.
      Investigations carried out included fundus fluorescein angiography, optical
      coherence tomography (OCT) of the macula and optic disc, perimetry, and
      electrophysiological study. Electrolyte levels were measured in retro-oil fluid
      and compared with their levels in the vitreous humor of patients who underwent
      vitrectomy for macular holes, floaters, dropped intraocular lenses, or dropped
      crystalline lens fragments. RESULTS: Visual acuity levels dropped by at least 2
      Snellen chart lines. None of the 12 cases had macular detachment at any stage.
      Fundus fluorescein angiography and OCT results were unremarkable in most of the
      cases. Mean levels of electrolytes in retro-oil fluids and vitreous humor were
      similar. CONCLUSION: Visual loss is a possible complication after SO use or
      removal. This still remains a mysterious issue which needs further research and
      investigation.

PMID- 28445870
TI  - KLK4 Gene and Dental Decay: Replication in a South Brazilian Population.
AB  - OBJECTIVE: The objective of this research was to identify and replicate the
      participation of KLK4 gene polymorphisms in the susceptibility to dental decay.
      METHODS: A total of 200 patients were recruited using ICDAS criteria - 100 of
      them with dental caries and 100 with no history of the disease. Buccal cells were
      collected and the DNA was extracted and amplified using PCR. RESULTS: During the
      descriptive analysis, the variables ethnicity, biofilm, and gingivitis and the
      markers rs2242670 and rs2978642 were statistically significant. In the
      multivariate analysis, the marker rs2242670 and the variable biofilm maintained
      statistical significance. CONCLUSION: Genetic variations in the KLK4 gene may
      contribute to dental decay.

PMID- 28445872
TI  - Successful Management of Decitabine prior to Full-Dose Idarubicin and Cytarabine
      in the Treatment of Refractory/Recurrent Acute Myeloid Leukemia.
AB  - AIMS: To investigate the safety and efficacy of the triple therapy of decitabine,
      idarubicin, and cytarabine in the treatment of refractory or recurrent acute
      myeloid leukemia (R/R AML). METHODS: We conducted a single-center retrospective
      study in which decitabine treatment was administered prior to full-dose
      idarubicin and cytarabine (D-IA) for 21 R/R AML patients. RESULTS: After 1 cycle
      of D-IA, 10/21 (47.6%) patients experienced a complete remission (CR) and 2/21
      (9.5%) showed a partial response. There was a 1-month response rate (RR) in 12/21
      patients (57.14%); these patients achieved CR after 2 cycles of D-IA. Five of
      these 12 (40%) patients then received sequential allogeneic stem cell
      transplantation. At the last follow-up date, 9/21 (42.8%) patients had survived,
      and 7/21 (33.3%) were in continuous CR. Hematological toxicity and infections
      were the most prominent toxicities of this regimen. Other toxicities included
      nausea, vomiting, bleeding, and liver enzyme abnormalities. No mortalities were
      recorded due to treatment-related toxicity during remission. CONCLUSIONS: The
      combination was well tolerated, and the RR was encouraging. Our study suggests
      that D-IA may offer a novel and potentially effective treatment regimen for R/R
      AML patients.

PMID- 28445871
TI  - Three-Year Clinical Outcome of Patients with Coronary Disease and Increased Event
      Risk Treated with Newer-Generation Drug-Eluting Stents: From the Randomized DUTCH
      PEERS Trial.
AB  - OBJECTIVE: Limited data is available on the long-term outcome of patients with
      increased cardiovascular event risk, treated with newer-generation durable
      polymer drug-eluting stents (DES). METHODS: We therefore assessed 3-year follow
      up data of high-risk versus low- to intermediate-risk patients of the randomized
      DUTCH PEERS trial (NCT01331707). In both risk groups we also compared patients
      treated with Resolute Integrity versus Promus Element DES. Patients were
      categorized as "high-risk" if they met >=1 of the following criteria: (1)
      diabetes (17.9%); (2) previous myocardial infarction (21.9%); (3) previous
      coronary revascularization (25.8%); (4) chronic renal failure (3.5%); (5) left
      ventricular ejection fraction <=30% (1.5%); and (6) age >=75 years (17.3%).
      RESULTS: At the 3-year follow-up, the incidence of the composite endpoint target
      vessel failure (TVF) (13.2 vs. 7.5%; logrank p < 0.001) and 2 of its components -
      cardiac death (4.7 vs. 1.5%; logrank p < 0.001) and target vessel
      revascularization (7.3 vs. 4.7%; logrank p = 0.03) - was higher in high-risk (n =
      957) versus low- to intermediate-risk patients (n = 854). Among high-risk
      patients, treatment with Resolute Integrity (n = 481) and Promus Element stents
      (n = 476) was similarly safe and efficacious (TVF: 13.3 vs. 13.1%; logrank p =
      0.95; definite-or-probable stent thrombosis: 1.7 vs. 1.7%; logrank p = 1.00).
      CONCLUSIONS: The newer-generation Resolute Integrity and Promus Element stents
      showed similar results in terms of safety and efficacy for treating high-risk
      patients, who had significantly higher event rates than patients with low-to
      intermediate risk.

PMID- 28445873
TI  - Pregnancy Outcomes in Patients with Glomerular Disease Attending a Single
      Academic Center in North Carolina.
AB  - BACKGROUND: Contemporary data regarding pregnancy outcomes in US patients with
      primary glomerular diseases are lacking. We aimed to report fetal and maternal
      outcomes among women with biopsy-proven primary glomerular disease who received
      obstetric care at a single large academic US center. METHODS: All women with a
      biopsy-confirmed primary glomerular disease diagnosis and without end-stage
      kidney disease who received obstetric care at the University of North Carolina
      (UNC) Hospitals (1996-2015) were identified using the Glomerular Disease
      Collaborative Network registry and the UNC Hospitals Perinatal Database. The
      primary study outcome was perinatal death (stillbirth at >20 weeks or neonatal
      death). Secondary outcomes included premature birth (<37 weeks), birth weight,
      preeclampsia, and kidney function changes (postpartum vs. baseline).
      Demographics, clinical characteristics, and outcomes were compared across
      glomerular disease subtypes. RESULTS: Among 48 pregnancies in 43 women (IgA
      nephropathy n = 17, focal segmental glomerulosclerosis [FSGS] n = 16, membranous
      nephropathy n = 6, minimal change disease n = 4), 13% of pregnancies resulted in
      perinatal death and 48% of babies were born prematurely. From a maternal
      perspective, 33% of pregnancies were complicated by preeclampsia, 39% by a
      doubling of urinary protein, and 27% by a >=50% increase in serum creatinine.
      Outcome differences across glomerular disease subtypes were not statistically
      significant, although decline in kidney function appeared most frequent in FSGS.
      CONCLUSION: Adverse pregnancy outcomes are frequently observed in women with
      glomerular disease. The independent influence of glomerular disease subtype on
      outcomes requires further study. More widespread reporting and analysis of
      pregnancy outcomes in women with glomerular disease are urgently needed.

PMID- 28445874
TI  - Erythropoietin Treatment Exacerbates Moderate Injury after Hypoxia-Ischemia in
      Neonatal Superoxide Dismutase Transgenic Mice.
AB  - The neonatal brain is highly susceptible to oxidative stress as developing
      endogenous antioxidant mechanisms are overwhelmed. In the neonate, superoxide
      dismutase (SOD) overexpression worsens hypoxic-ischemic injury due to H2O2
      accumulation in the brain. Erythropoietin (EPO) is upregulated in 2 phases after
      HI, early (4 h) and late (7 days), and exogenous EPO has been effective in
      reducing the injury, possibly through reducing oxidative stress. We hypothesized
      that exogenous EPO would limit injury from excess H2O2 seen in SOD1
      overexpressing mice, and thus enhance recovery after HI. We first wanted to
      confirm our previous findings in postnatal day 7 (P7) SOD-tg (CD1) mice using a
      P9 model of the Vannucci procedure of HI with SOD-tg mice from a different
      background strain (C57Bl/6), and then determine the efficacy of EPO treatment in
      this strain and their wild-type (WT) littermates. Thus, mice overexpressing
      copper/zinc SOD1 were subjected to HI, modified for the P9 mouse, and recombinant
      EPO (5 U/g) or vehicle (saline) was administered intraperitoneally 3 times: at 0
      h, 24 h, and 5 days. Injury was assessed 7 days after HI. In addition, protein
      expression for EPO and EPO receptor was assessed in the cortex and hippocampus 24
      h after HI. With the moderate insult, the SOD-tg mice had greater injury than the
      WT overall, confirming our previous results, as did the hippocampus and striatum
      when analyzed separately, but not the cortex or thalamus. EPO treatment worsened
      injury in SOD-tg overall and in the WT and SOD-tg hippocampus and striatum. With
      the more severe insult, all groups had greater injury than with the moderate
      insult, but differences between SOD-tg and WT were no longer observed and EPO
      treatment had no effect. Increased protein expression of EPO was observed in the
      cortex of SOD-tg mice given recombinant human EPO compared to SOD-tg given
      vehicle. This study confirms our previous results showing greater injury with SOD
      overexpression in the neonatal brain after HI at P7 in a different strain. These
      results also suggest that EPO treatment cannot ameliorate the damage seen in
      situations where there is excess H2O2 accumulation, and it may exacerbate injury
      in settings of extreme oxidative stress.

PMID- 28445875
TI  - Double-Incision Approach and Early Rehabilitation in a Complicated Bicondylar
      Tibial Plateau Fracture: A Case Report.
AB  - OBJECTIVE: The main goal of this case was to report the treatment of bicondylar
      fractures of the tibial plateau and the restoration of the metaphyseo-diaphyseal
      dissociation. CLINICAL PRESENTATION AND INTERVENTION: A 54-year-old male who was
      cycling had a road accident that caused a closed fracture of the right tibial
      plateau and proximal fibula diagnosed by X-rays. The patient underwent surgery
      and was immobilized with a long-leg splint for 4 weeks. After immobilization,
      aggressive rehabilitation was done. Progressive quadriceps strengthening,
      movements to improve symmetrical weight bearing, and functional activities were
      performed. The patient improved muscle strength and obtained high scores for gait
      and balance in a relatively short time. CONCLUSION: In this report, a bicondylar
      tibial fracture treated with a two-incision approach and a double-plate
      osteosynthesis provided strong fracture stabilization and thereby allowed an
      early mobilization with aggressive rehabilitation.

PMID- 28445876
TI  - Impact of the Reclassification of the Non-Invasive Follicular Variant of
      Papillary Carcinoma as Benign on the Malignancy Risk of the Bethesda System for
      Reporting Thyroid Cytopathology: A Meta-Analysis Study.
AB  - OBJECTIVES: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)
      established diagnostic categories for cytologic specimens of the thyroid. Each
      category was associated with an estimated risk of malignancy. Recently, the non
      invasive follicular variant of papillary thyroid carcinoma has been reclassified
      as benign. This reclassification may alter the malignancy risk of TBSRTC
      diagnostic categories. STUDY DESIGN: A literature search was made for all studies
      investigating the effect of reclassification of some non-invasive follicular
      variant papillary thyroid carcinomas as benign on the malignancy risk associated
      with TBSRTC categories. The authors calculated the malignancy risk for TBSRTC
      categories in a series of 315 thyroid aspirates when the non-invasive follicular
      variant of papillary thyroid carcinoma was considered benign. A meta-analysis of
      malignancy risk data for the 3 published studies and the current study was
      performed. RESULTS: The meta-analysis showed that the malignancy risk was reduced
      for all TBSRTC categories except the "non-diagnostic" category. The reduction in
      malignancy risk was greatest in the categories "suspicious for malignancy" and
      "atypia/follicular lesion of undetermined significance." CONCLUSION: A meta
      analysis of all pertinent studies demonstrated that re-categorization of the non
      invasive follicular variant of papillary thyroid carcinoma as benign reduces the
      malignancy risk in the majority of TBSRTC categories.

PMID- 28445877
TI  - Benign Exocrine Pancreatic Diseases in Inflammatory Bowel Diseases.
AB  - BACKGROUND: Data regarding the involvement of the pancreas during the course of
      inflammatory bowel disease (IBD) are scarce and conflicting. AIM: To assess the
      frequency of benign pancreatic diseases, that is, acute pancreatitis, chronic
      pancreatitis (CP), and autoimmune pancreatitis (AIP), in a population with IBD.
      METHODS: A search for patients with IBD who presented at our hospital between
      January 2006 and January 2015 with a diagnosis of IBD was carried out. PATIENTS:
      A total of 5,242 patients with IBD were included in this study (2,838 males,
      54.1%, and 2,404 females, 45.9%, mean age 43.7 years, range 18-101 years). Of
      these 5,242 patients, 3,201 (61.1%) had Crohn's disease and 2,041 (38.9%) had
      ulcerative colitis (UC). RESULTS: Thirteen patients developed benign pancreatic
      diseases (0.2%). Eight patients had acute pancreatitis (0.2%; 4 in the Crohn's
      disease group and 4 in the UC group), 3 had CP (0.1%, 2 in the Crohn's disease
      group and 1 in the UC group), 2 had AIP (0.04%), all in the group of diffuse UC
      (p = 0.321). CONCLUSIONS: The frequency of benign pancreatic disease was not high
      in patients with IBD and was probably similar to that seen in the general
      population.

PMID- 28445878
TI  - Differential Allelic Expression of HTR1B in Suicide Victims: Genetic and
      Epigenetic Effect of the Cis-Acting Variants.
AB  - OBJECTIVES: In the present study, we tested the allelic imbalance of the C861G
      single nucleotide polymorphism (SNP) of HTR1B in the frontal cortex of suicide
      victims. METHODS: The study was conducted using 3 sets of samples. First, C861G
      allele-specific mRNA levels in the frontal cortex were compared between suicide
      (n = 13) and nonsuicide controls (n = 13) from the Stanley Medical Research
      postmortem brain collection. Second, we tested common variants in the HTR1B
      promoter for linkage disequilibrium (LD) with the C861G variant in an unrelated
      sample of suicide attempters (SA; n = 38) and non-SA (NSA; n = 42). Finally, we
      performed a family-based association study of the C861G and promoter variants in
      162 nuclear families using suicidal behavior severity scores as phenotype.
      RESULTS: We observed no alterations in the C/G expression ratio in suicide
      victims compared to nonsuicide controls (p = 0.370). When comparing the LD
      between the C861G and cis-acting SNPs, we did not find any differences in SA and
      NSA. There was no association between preferential transmission of cis-acting
      SNPs and suicidal behavior severity scores in both maternal and paternal meiosis.
      CONCLUSIONS: We found several promoter variants in LD that may potentially
      influence the allelic imbalance in the C861G variant. However, no evidence of
      allelic imbalance nor parent-of-origin effects of the C861G variant was observed
      in suicidal behavior. Further research is required to assess this marker in
      larger cohorts.

PMID- 28445879
TI  - Cytokine and Chemokine Profiles in Patients with Neuromyelitis Optica Spectrum
      Disorder.
AB  - OBJECTIVE: To screen cytokines and chemokines and determine their dynamic changes
      in the serum and cerebrospinal fluid (CSF) of patients with neuromyelitis optica
      spectrum disorder (NMOSD). METHODS: Eight NMOSD with seropositive aquaporin-4
      antibody (AQP4-IgG) were enrolled, as well as 8 matched patients with multiple
      sclerosis (MS) and 8 with noninflammatory neurological diseases, who were
      included as controls. In total, 102 cytokines and 34 chemokines were detected in
      the CSF and serum of NMOSD patients and controls. RESULTS: CSF interleukin (IL)
      17A levels were significantly higher in NMOSD patients in the relapsing phase
      (27.15 +/- 11.33) than in those in the remitting phase (10.04 +/- 3.11, p =
      0.0017), and patients with MS (14.72 +/- 3.20, p = 0.0283) and other controls
      (10.39 +/- 11.38, p = 0.0021). CSF IL-6 levels were higher in the NMOSD patients
      in the relapsing phase (12.23 +/- 3.47) than in those in the remitting phase
      (5.87 +/- 2.78, p = 0.0001), and MS patients (7.38 +/- 2.35, p = 0.0033) and
      other controls (7.50 +/- 0.37, p = 0.0043). CSF CCL19 levels were also
      significantly higher in NMOSD patients in the relapsing phase (35.87 +/- 27.07)
      than in those in the remitting phase (10.71 +/- 3.62, p = 0.0215). Serum IL-19
      levels were lower in NMOSD patients in the relapsing phase (6.23 +/- 1.95) than
      in those in the remitting phase (10.72 +/- 4.46, p = 0.0092). Further, there was
      a positive, significant correlation between serum IL-9 concentration and the
      Expanded Disability Status Scale score in the NMOSD patients in the relapsing
      phase (p = 0.04). CONCLUSION: In addition to IL-6 and IL-17A, IL-16 and CCL19 act
      as proinflammatory cytokines/chemokines, while IL-19 plays a protective role in
      NMOSD pathogenesis.

PMID- 28445880
TI  - Heating of Newborn Infants due to Blue Light-Emitting Diode Fibreoptic
      Phototherapy Pads.
AB  - BACKGROUND: Surface temperatures of fibreoptic phototherapy pads using a high
      intensity blue light-emitting diode (LED) light source have not been studied.
      OBJECTIVES: The aim of this study was to measure the temperature of LED
      fibreoptic phototherapy pads during phototherapy in a bench-top study, and to
      determine temperature effects on babies during phototherapy. METHODS: A
      commercially available LED fibreoptic phototherapy system was tested. In a bench
      top setting, pad surface temperatures were measured before, during and after a 12
      h period of phototherapy (10 different LED light box-pad combinations). A
      prospective, cohort study of well babies at >34 weeks' gestation receiving
      phototherapy was then conducted to determine changes in pad and body temperatures
      during a 90-min phototherapy period. RESULTS: In the bench-top study, the mean
      (95% CI) pad temperature was 21.8 degrees C (21.5-22.1) before lights, 27.0
      degrees C (26.5-27.5) after 12 h of lights, and 22.1 degrees C (21.9-22.4) 8 h
      after turning off the lights (F = 366.1, p < 0.0005). The magnitude of change in
      pad temperature with phototherapy was linearly correlated with irradiance (r =
      0.89, p < 0.0005). The pad plastic covering absorbed 13% of blue light from
      fibres. In the clinical study, the warmest pad temperature during phototherapy
      was 38.9 degrees C. Axillary temperature increased by a mean (95% CI) of 0.3
      degrees C (0.1-0.5), p < 0.019, and exceeded 37.5 degrees C in 4 babies.
      CONCLUSIONS: LED fibreoptic phototherapy pads are heated by high-intensity blue
      light. The thermal environment and temperature of babies should be monitored
      closely during LED fibreoptic phototherapy. A temperature probe placed between
      the skin and the pad will not accurately reflect the core temperature during
      fibreoptic phototherapy.

PMID- 28445881
TI  - Absence of Decline of Kidney Function in Human Immunodeficiency Virus-Infected
      Patients Under Routine Clinical Management.
AB  - BACKGROUND: Since the introduction of antiretroviral therapy (ART), human
      immunodeficiency virus (HIV)-infected patients have a drastically improved
      prognosis but at the same time they are also more affected by non-HIV related
      complications, such as chronic kidney disease. The objective of our study was to
      investigate the effect of proteinuria and tenofovir (TDF)-containing ART regimens
      on the temporal evolution of estimated glomerular filtration rate (eGFR).
      METHODS: Between April 2008 and October 2012, we enrolled 395 patients with a
      complete renal evaluation among patients from the ANRS C03 Aquitaine cohort, a
      prospective hospital-based cohort of HIV-1-infected patients under routine
      clinical management in southwestern France. eGFR was estimated at each patient
      follow-up visit. A linear mixed model was used to analyze eGFR dynamics,
      accounting for change in TDF by modeling eGFR trajectory according to treatment
      periods. RESULTS: At inclusion, 56.7% of patients were treated with TDF
      containing ART regimens; prevalence of glomerular and tubular proteinuria was 7.9
      and 10.8% respectively. A 1-year increase of cumulative exposure to TDF was
      significantly associated with a mean eGFR decrease of 1.27 mL/min/1.73 m2 (95% CI
      [-2.14 to -0.41]). Only a urine protein to creatinine ratio >100 mg/mmol and/or a
      urine albumin to creatinine ratio >70 mg/mmol were associated with eGFR
      trajectory (mean slope 6.18 mL/min/1.73 m2 per year; 95% CI [2.71 to 9.65]),
      whereas TDF use was not associated with such eGFR temporal evolution. CONCLUSION:
      Decline in kidney function is limited under routine clinical management with
      monitoring of renal function and interventions including decision to continue or
      discontinue TDF.

PMID- 28445882
TI  - IUNS News.

PMID- 28445883
TI  - FENS News.

PMID- 28445884
TI  - Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and
      Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular
      Junction.
AB  - The development of the nervous system involves the initial overproduction of
      synapses, which promotes connectivity. Hebbian competition between axons with
      different activities leads to the loss of roughly half of the overproduced
      elements and this refines connectivity. We used quantitative immunohistochemistry
      to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the
      involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and
      the M1, M2, and M4 subtypes) and adenosine receptors (A1 and A2A subtypes) in the
      control of axonal elimination after the mouse levator auris longus muscle had
      been exposed to selective antagonists in vivo. In a previous study we analyzed
      the role of each of the individual receptors. Here we investigate the additive or
      occlusive effects of their inhibitors and thus the existence of synergistic
      activity between the receptors. The main results show that the A2A, M1, M4, and
      A1 receptors (in this order of ability) delayed axonal elimination at P7. M4
      produces some occlusion of the M1 pathway and some addition to the A1 pathway,
      which suggests that they cooperate. M2 receptors may modulate (by allowing a
      permissive action) the other receptors, mainly M4 and A1. The continued action of
      these receptors (now including M2 but not M4) finally promotes axonal loss at P9.
      All 4 receptors (M2, M1, A1, and A2A, in this order of ability) are necessary.
      The M4 receptor (which in itself does not affect axon loss) seems to modulate the
      other receptors. We found a synergistic action between the M1, A1, and A2A
      receptors, which show an additive effect, whereas the potent M2 effect is largely
      independent of the other receptors (though can be modulated by M4). At P9, there
      is a full mutual dependence between the A1 and A2A receptors in regulating axon
      loss. In summary, postnatal axonal elimination is a regulated multireceptor
      mechanism that involves the cooperation of several muscarinic and adenosine
      receptor subtypes.

PMID- 28445885
TI  - Patterns of Microglial Cell Activation in Alzheimer Disease and Frontotemporal
      Lobar Degeneration.
AB  - AIMS: Microglia-driven neuroinflammation can play an important role in the
      pathophysiology of neurodegenerative disorders. In this study, we sought to
      characterize the distribution of microglial cell activation in 2
      neurodegenerative dementias with distinct protein signatures, Alzheimer disease
      (AD) and frontotemporal lobar degeneration (FTLD) of the TDP subtype, and to
      determine if there was an anatomical correlation with the phenotypes most
      commonly associated with these conditions. METHODS: The distribution and extent
      of microglial cell activation was assessed semiquantitatively in the hippocampal
      formation, cortical gray matter, and subcortical white matter of CD68
      immunostained sections of the frontal, temporal, parietal, and occipital cortices
      from 15 pathologically confirmed cases of AD, 13 cases of FTLD, and 18 controls.
      RESULTS: Significantly higher levels of microglial cell activation occurred in
      the subiculum in AD and FTLD than in controls. Additionally, AD had higher
      microglial activation in the CA1 and FTLD in the hippocampal white matter than
      the controls. Microglial activation was greater in the dentate gyrus molecular
      layer in AD than in FTLD. In the cortical regions, the 2 pathological groups
      differed only in frontal white matter, with the FTLD group showing higher
      microglial scores. FTLD showed higher microglial activation in the white matter
      compared to the respective gray matter in the entorhinal, temporal, and frontal
      regions. CONCLUSIONS: Our work expands the knowledge of the distribution and
      magnitude of microglial activation in these disorders. Additionally, we found
      some microglial circuit-specific patterns that could help to explain some of the
      clinical overlap between AD and FTLD-TDP, namely in memory deficits.

PMID- 28445886
TI  - The Association of Five-Year Changes in the Levels of N-Terminal Fragment of the
      Prohormone Brain-Type Natriuretic Peptide (NT-proBNP) with Subsequent Heart
      Failure and Death in Patients with Stable Coronary Artery Disease: The Heart and
      Soul Study.
AB  - BACKGROUND: The N-terminal fragment of the prohormone brain-type natriuretic
      peptide (NT-proBNP) is a powerful predictor of adverse outcomes in patients with
      coronary artery disease (CAD). However, little is known regarding the prognostic
      significance of longitudinal changes in NT-proBNP levels. METHODS: We evaluated
      the ability of 5-year changes in NT-proBNP levels to predict subsequent heart
      failure (HF) hospitalization or cardiovascular (CV) death in 635 participants
      with stable CAD enrolled in the Heart and Soul Study. RESULTS: The median (IQR) 5
      year change in NT-proBNP was 50 pg/mL (-5 to +222). During an average of 4.0 +/-
      1.4 years follow-up (i.e., 9 years from the baseline measurement), there were 67
      events. Participants with 5-year changes in the highest quartile (>= 223 pg/mL
      increase in NT-proBNP) had an almost 4-fold greater risk of subsequent HF or CV
      death than those in the lowest quartile of <=-5 pg/mL (HR 3.8; 95% CI 2.0-7.3; p
      < 0.001). This association remained strong after adjustment for demographic
      variables, comorbidities, left ventricular mass index, systolic and diastolic
      function, and baseline and follow-up NT-proBNP levels (HR 3.9; 95% CI 1.1-13.4; p
      = 0.01). CONCLUSION: Changes in NT-proBNP levels at 5 years predict subsequent HF
      or CV death in patients with stable CAD, independent of other prognostic markers,
      including baseline and follow-up NT-proBNP levels. A stable NT-proBNP level
      predicts a low risk of subsequent events.

PMID- 28445887
TI  - Use of Phosphorus Binders among Non-Dialysis Chronic Kidney Disease Patients and
      Mortality Outcomes.
AB  - BACKGROUND: Whether the benefits of phosphorus binders extend to those without
      end stage renal disease is uncertain. Among a large diverse non-dialysis chronic
      kidney disease (CKD) population with hyperphosphatemia, we sought to evaluate
      phosphorus binder use and compare mortality risk between patients prescribed and
      not prescribed binders. METHODS: A retrospective cohort study within an
      integrated health system (January 1, 1998 - December 31, 2012) among CKD patients
      (age >=18) was performed. Non-dialysis CKD patients with 2 separate estimated
      glomerular filtrate rate (eGFR) <30 mL/min/1.73 m2 and serum phosphorus >=5.0
      mg/dL within 180 days of eGFR were included. Multivariable cox proportional
      hazards and inverse probability of treatment-weighted models were used to
      estimate mortality hazard ratios (HRs) for patients who received phosphorus
      binders compared to no binders. RESULTS: Among 10,165 study patients, 2,733
      subjects (27%) received phosphorus binders. Compared to the no-phosphorus-binder
      group, the binder group had mortality HRs (95% CI) of 0.86 (0.79-0.94) and 0.86
      (0.80-0.93) using traditional multivariable and inverse probability of treatment
      weighted models respectively. Sensitivity analyses removing patients who were
      prescribed binders >180 days after index date revealed no difference in mortality
      between those with binders and with no binders. CONCLUSION: Our findings from a
      real-world clinical environment revealed that 27% of hyperphosphatemic non
      dialysis CKD patients were prescribed binders. They also had lower risk of
      mortality compared to those not prescribed phosphorus binders. However, the lower
      mortality risk was not observed when we accounted for immortal time bias. Whether
      phosphorus binder use in CKD improves survival remains to be determined.

PMID- 28445888
TI  - Differential Effects of Inflammatory and Psychosocial Stress on Mood,
      Hypothalamic-Pituitary-Adrenal Axis, and Inflammation in Remitted Depression.
AB  - BACKGROUND/AIMS: Major depressive disorder (MDD) is highly recurrent. This may be
      due to increased stress sensitivity after remission. Both inflammatory and
      psychosocial stressors are implicated in the pathogenesis of MDD, but the
      additive or differential effect is unclear. METHODS: We conducted a single-blind
      placebo-controlled study to investigate the effects of inflammatory stress (i.e.,
      typhoid vaccination), psychosocial stress (i.e., Trier Social Stress Test
      [TSST]), or a combination of both in women (25-45 years old) with (partially)
      remitted recurrent MDD (n = 21) and healthy female controls (n = 18). We
      evaluated the effect on mood measured by the Profile of Mood States, markers of
      the hypothalamic-pituitary-adrenal (HPA) axis activity, and inflammatory system
      activation. The study was performed during 2 testing days, separated by a washout
      of 7-14 days. In a crossover design, subjects received one of the interventions
      on one day and placebo on the other. RESULTS: A lowering of mood was seen in
      patients (beta [95% CI] = -4.79 [-6.82 to -2.75], p < 0.001) only after
      vaccination, but not after the TSST or the combination; this effect was not
      observed in controls. Controls experienced a significantly different response on
      adrenocorticotropic hormone (ACTH) after vaccination, with a general rise in ACTH
      not observed in patients. In both groups, the TSST activated the HPA axis and
      suppressed the inflammatory parameters. CONCLUSIONS: There is a differential
      effect of inflammatory and psychosocial stress on mood and HPA axis activation in
      patients with remitted recurrent MDD. This may be an interesting treatment target
      in MDD.

PMID- 28445889
TI  - Genetic Polymorphisms in Aromatase (cyp19a1) Are Not Associated with Gonadal
      Phenotypes in Red-Eared Slider Turtle Hatchlings Developed at a Pivotal
      Temperature.
AB  - Embryonic gonad sex in many reptilian species is determined by the incubation
      temperature of the egg, a differentiation process known as temperature-dependent
      sex determination (TSD). Incubation at the pivotal temperature (PvT) results in
      approximately an equal number of offspring of both sexes. We investigated the
      potential contribution of genetic variations that drives the gonadal
      differentiation into testes or ovaries under this temperature in the red-eared
      slider turtle (Trachemys scripta). Four male and 4 female hatchlings of eggs that
      had been incubated at the PvT were examined for polymorphisms at an approximately
      23-kb region of the aromatase (cyp19a1) gene. By aligning the red-eared slider
      aromatase gene to a reference genome of the western painted turtle (Chrysemys
      picta bellii), we discovered 22 exonic and 1,268 intronic polymorphisms. Of
      these, 12 (55%) exonic polymorphisms were unique to the individuals of the red
      eared slider; 10 were synonymous and 2 were nonsynonymous changes. We found no
      pattern in these genetic variants as well as intronic variants that are
      consistently different between male and female hatchlings at the PvT. Overall,
      our study suggests that polymorphisms within the aromatase gene - at least by
      themselves - do not constrain the gonad sex differentiation in embryos developed
      at the PvT.

PMID- 28445890
TI  - Non-Cystic Fibrosis Bronchiectasis: from Programmatic Management to Personalized
      Medicine.

PMID- 28445891
TI  - Guidelines for Idiopathic Pulmonary Fibrosis: Everything Flows.

PMID- 28445892
TI  - Feasibility of Modified FOLFOX in Elderly Patients Aged >=80 Years with
      Metastatic Gastric Cancer or Colorectal Cancer.
AB  - OBJECTIVE: The aim of this study was to assess the feasibility of a modified
      FOLFOX regimen as first-line treatment in elderly patients with metastatic
      gastric cancer (GC) or colorectal cancer (CRC). METHODS: We included chemotherapy
      naive patients over 80 years old with metastatic GC or CRC in our study. From
      September 2008 to November 2014, 28 consecutive patients were enrolled and
      treated with modified FOLFOX. RESULTS: The study population consisted of an equal
      number of GC and CRC patients. The median age was 82.2 years in the GC group and
      81.1 years in the CRC group. The total number of administered cycles was 89 (with
      a median of 6 per patient) in the GC group and 112 (with a median of 8 per
      patient) in the CRC group. Median progression-free survival (PFS) and overall
      survival (OS) were 5.4 and 6.6 months in the GC group and 7.3 and 8.1 months in
      the CRC group, respectively. There was no significant difference in PFS (p =
      0.941) and OS (p = 0.238) between the GC and the CRC group. The 1-year survival
      rates were 35.7% with GC and 42.9% with CRC. Common grade 3/4 hematology
      toxicities were neutropenia (10.7%) and anemia (14.3%). Salvage chemotherapy was
      administered to 1 patient with GC and 7 patients with CRC. CONCLUSIONS: The
      modified FOLFOX regimen can be cautiously considered as a first-line treatment
      option in extremely elderly patients with metastatic GC or CRC.

PMID- 28445893
TI  - Early Mortality Associated with Inpatient versus Outpatient Hemodialysis
      Initiation in a Large Cohort of US Veterans with Incident End-Stage Renal
      Disease.
AB  - BACKGROUND: Mortality in the immediate post-hemodialysis transition period is
      extremely high. Many end-stage renal disease (ESRD) patients in the US start
      dialysis in an inpatient setting, but the characteristics of patients starting
      dialysis as inpatients, and the association of inpatient hemodialysis transition
      with mortality remain unclear. METHODS: We examined 48,261 US veterans who
      transitioned to hemodialysis between October 2007 and September 2011.
      Associations of inpatient hemodialysis starting with all-cause mortality were
      examined in Cox proportional hazard models, with adjustments for demographics,
      comorbidities, vascular access type, pre-dialysis nephrology care and medication
      use, and last pre-ESRD estimated glomerular filtration rate and hemoglobin.
      RESULTS: A total of 22,338 (46.3%) patients received the first hemodialysis
      treatment in an inpatient setting. Inpatient hemodialysis transition was
      associated with older age, presence of a tunneled catheter, higher comorbidity
      burden, and lack of pre-dialysis nephrology care. A total of 8,674 patients died
      (mortality rate 405/1,000 patient-years, 95% CI 397-413) during the first 6
      months after transition to hemodialysis. The starting of inpatient vs. outpatient
      hemodialysis was associated with significantly higher crude all-cause mortality,
      but this association was attenuated after multivariable adjustments. CONCLUSIONS:
      Transition to hemodialysis in an inpatient setting is more common in older and
      sicker individuals, and in patients without pre-dialysis nephrology care and
      those who used a catheter for vascular access. Future studies are needed to
      determine if a higher proportion of patients could start hemodialysis treatment
      in outpatient clinics, through interventions targeting modifiable risk factors
      such as timely vascular access placement or earlier nephrology referrals.

PMID- 28445894
TI  - Radiologic Differences between Human Papillomavirus-Related and Human
      Papillomavirus-Unrelated Oropharyngeal Carcinoma on Diffusion-Weighted Imaging.

PMID- 28445895
TI  - [Sports Injuries and Illnesses of the German National Team during the 2016
      Olympic Summer Games in Rio de Janeiro].

PMID- 28445896
TI  - Total Serum Antioxidant Capacity in Healthy Normal Weight and Asymptomatic
      Overweight Adults.
AB  - Obesity and overweight are major contributors to the burden of chronic disease.
      Both are defined as abnormal or excessive fat accumulation and by increased
      production of free radicals leading to oxidative stress. The aim of the present
      study was to evaluate whether overweight and fat accumulation is associated with
      serum total antioxidant capacity (TAC) in men and women, irrespective of
      nutritional habits, nutrient intakes, physical activity, smoking, and other
      confounders, which may be responsible for modifying the association between serum
      TAC and overweight/obesity measures. This cross-sectional study was conducted on
      60 normal weight and 60 overweight adults aged 25-49. All participants underwent
      standard anthromorphological measurements of body composition, blood pressure and
      biochemical measurements, aerobic capabilities assessment and dietary intake
      evaluation. TAC was measured by using the photochemioluminescence method. All
      data were analysed with SPSS software. Men had higher values of TAC than women
      and concentrations of TAC were significantly higher in overweight subjects
      compared to normal weight subjects. In the present study TAC tended to be
      increased by various metabolic risk factors, especially overweight/obesity
      parameters (body mass index, body fat), inflammation and increased serum levels
      of Cysteine, irrespective of nutritional habits, nutrient intakes, physical
      activity and smoking. Overweight and obesity at an early stage may stimulate TAC.
      Therefore, the elevation of TAC in overweight adults may be a compensatory
      response to oxidative stress, generated by reactive oxygen species.

PMID- 28445897
TI  - Adrenal Vein Catecholamine Levels and Ratios: Reference Intervals Derived from
      Patients with Primary Aldosteronism.
AB  - Phaeochromocytoma localisation is generally reliably achieved with modern imaging
      techniques, particularly in sporadic cases. On occasion, however, there can be
      diagnostic doubt due to the presence of bilateral adrenal abnormalities,
      particularly in patients with mutations in genes predisposing them to the
      development of multiple phaeochromocytomas. In such cases, surgical intervention
      is ideally limited to large or functional lesions due to the long-term
      consequences associated with hypoadrenalism. Adrenal venous sampling (AVS) for
      catecholamines has been used in this situation to guide surgery, although there
      are few data available to support diagnostic thresholds. Retrospective analyses
      of AVS results from 2 centres were carried out. A total of 172 patients (88 men,
      84 women) underwent AVS under cosyntropin stimulation for the diagnosis of
      established primary aldosteronism (PA) with measurement of adrenal and peripheral
      venous cortisol, aldosterone and catecholamines. Six patients (3 men, 3 women)
      with phaeochromocytoma underwent AVS for diagnostic purposes with subsequent
      histological confirmation. Reference intervals for the adrenal venous
      norepinephrine to epinephrine ratio were created from the PA group. Using the
      97.5th centile (1.21 on the left, 1.04 on the right), the false negative rate in
      the phaeochromocytoma group was 0%. In conclusion, this study describes the
      largest dataset of adrenal venous catecholamine measurements and provides
      reference intervals in patients without phaeochromocytoma. This strengthens the
      certainty with which conclusions related to adrenal venous sampling for
      catecholamines can be drawn, acknowledging the procedure is not part of the
      routine diagnostic workup and is an adjunct for use only in difficult clinical
      cases.

PMID- 28445898
TI  - Dramatic Changes Over Time of Methamphetamine Intake in a German, HIV-Positive,
      Sample of Men who have Sex with Men (MSM).

PMID- 28445899
TI  - Evidence-Based Guidelines for the Pharmacologic Management of Methamphetamine
      Dependence, Relapse Prevention, Chronic Methamphetamine-Related, and Comorbid
      Psychiatric Disorders in Post-Acute Settings.
AB  - The increasing abuse of the street drug crystal meth (methamphetamine) in many
      countries worldwide has resulted in a growing demand to treat patients who have
      acquired a methamphetamine-related disorder. The results of a systematic
      literature search which led to the consensus-based recommendations by the Working
      Group of the German Agency for Quality in Medicine (Arztliches Zentrum fur
      Qualitat in der Medizin - AZQ) are presented. Pharmacological treatments were
      reviewed in 58 out of the 103 publications included. They were mainly randomized
      controlled trials (RCT). Despite increased research activities, none of the
      medications studied demonstrated a convincing and consistent effect on abstinence
      rates, despite some having an impact on craving and retention rates or symptom
      control. In addition, as yet there is no sufficient evidence available for
      dopamine analogue treatment ("substitution") after the initial withdrawal-period.
      Methamphetamine-related, post-acute persistent or comorbid syndromes such as
      methamphetamine-associated psychosis (MAP), depressive syndromes, anxiety, and
      sleep disorders are usually treated in a symptom-oriented manner. Risks of
      interactions with methamphetamine have to be taken in account when prescribing
      medications with doubtful efficacy. Further research is warranted.

PMID- 28445900
TI  - Central and Peripheral Glucagon Reduces Hyperlipidemia in Rats and Hamsters.
AB  - Increased lipid levels in blood contribute to increasing the risk of diabetic
      complications. Glucagon exerts lipid lowering effects in diabetic state. However,
      the mechanism behind the lipid reduction by glucagon independent of glucose
      homeostasis is not well understood. We assessed the actions of glucagon on lipid
      modulation in blood and markers in liver in hyperlipidemic hamsters and rats.
      Male Sprague Dawley rats and Golden Syrian hamsters on a hyperlipidemic diet for
      2 weeks were administered a single dose of glucagon by subcutaneous (SC, 150 and
      300 ug/kg) or intracerebroventricular (ICV, 15 and 30 ug/animal) route. Effect of
      acute treatment was observed on tyloxapol-induced hypertriglyceridemia, corn oil
      induced post-prandial lipemia, and bile flow. A repeated dose treatment by
      subcutaneous (300 ug/kg) or intracerebroventricular (30 ug/animal) route was done
      for 2 weeks, following which circulating and hepatic lipids, hepatic markers of
      lipid metabolism and bile flow were assessed. Acute administration of glucagon
      (SC and ICV) decreased triglyceride absorption, hepatic triglyceride secretion
      rate and increased excretion of cholesterol in bile fluid in dose related manner.
      Repeated dose treatment reduced circulating and hepatic lipids and mainly LDL,
      and enhanced cholesterol excretion in bile. In liver, expression of HMG-CoA
      reductase was reduced while that of ABCA1 was increased after repeated treatment,
      whereas pair fed group did not show significant changes when compared to the
      control group. These findings demonstrate that central as well as peripheral
      glucagon effectively reduces hyperlipidemia in rat and hamster model, by
      modulating hepatic lipid metabolism.

PMID- 28445901
TI  - Comparative Pharmacokinetics of Cholecalciferol in Dogs from 2 Different Oral
      Formulations Using Corrective Measures to Overcome Interference from Endogenous
      Cholecalciferol.
AB  - The aim of the preclinical investigation was to obtain single dose
      pharmacokinetics in dogs from 2 different oral cholecalciferol formulations using
      corrective measures to overcome the interference of endogenous cholecalciferol. 6
      dogs were fasted overnight and the following day received 60 000 IU dose
      cholecalciferol [reference, Eris(r), vs. test, Sunbless(r)] by oral dosing. Blood
      samples were collected on day 0 (baseline establishment) and after dosing on day
      1 up to 28 days. The serum samples were extracted using protein
      precipitation/solid phase extraction and analysed to determine cholecalciferol by
      LC-MS/MS assay with calibrators prepared from cholecalciferol free serum.
      Standard pharmacokinetic analysis was carried out to assess pharmacokinetic
      parameters. An un-paired t-test was employed for comparing statistical
      significance between formulations. Serum cholecalciferol concentration vs. time
      profiles for the 2 formulations was almost superimposable. None of the
      pharmacokinetic parameters showed statistically significant differences (p>0.05)
      between the 2 treatments. For example: Cmax (ng/mL) and AUCinf (ng.h/mL) derived
      after the baseline corrections were 708.65 and 38 877.18 for reference and 743.71
      and 40 665.51 for test, respectively. Pharmacokinetics of cholecalciferol was
      comparable between reference vs. test formulations. The procedures, baseline
      correction and employment of cholecalciferol devoid serum, can be readily adopted
      in future pharmacokinetic studies in animals or humans.

PMID- 28445902
TI  - A 3D-printed cap with sideoptics for colonoscopy: a randomized ex vivo study.
AB  - Background Adequate polyp detection is crucial to colonoscopy; however, detection
      can be impaired. In particular, flat polyps located behind folds or near the
      colonic flexures appear to be a problem. We present a cheap and easily adjustable
      3D-printed tool to enhance the view of a standard colonoscope using additional
      commercially available sideoptics. Materials and methods A cap adjustable to a
      standard endoscope was printed by a 3 D printer and had two microcameras fixed to
      offer two additional views. Fourteen endoscopists performed one standard and one
      sideoptic-enhanced colonoscopy in a randomized order. Flat lesions were simulated
      in an endoscopy training model. Time for withdrawal was measured, along with the
      number of flat lesions detected. Results Withdrawal time did not differ
      significantly between standard and sideoptic-enhanced colonoscopy (329 vs. 389
      seconds). The median number of detected flat lesions per endoscopic examination
      was significantly higher using the sideoptic tool (8 vs. 6.5; P = 0.001).
      Conclusions A 3D-printed sideoptic-enhanced cap including two microcameras may be
      a cheap, easy, and feasible add-on to improve adenoma detection rates in routine
      colonoscopy.

PMID- 28445903
TI  - Patient-reported adverse events after colonoscopy in Norway.
AB  - Background and aims Patient-reported outcome measures are increasingly important
      in healthcare. European guidelines have recommended inclusion of patient feedback
      to capture adverse events due to colonoscopy, but this is rarely implemented.
      Methods The Norwegian Quality Assurance network for endoscopy (Gastronet)
      collects patient-reported outcome for colonoscopies. Free-text comments on
      patient reports from January to December 2015 were characterized as positive or
      negative. All negative free-text comments were scrutinized for information that
      might suggest colonoscopy-related adverse events. We identified severe adverse
      events with and without admission to hospital. Results We included 16 552
      outpatient colonoscopies performed at 21 hospitals. A total of 11 248 procedures
      (68 %) were accompanied by a patient feedback report, of which 2628 (23 %) had
      free-text comments (2196 [20 %] characterized as positive and 432 [3.8 %] as
      negative). These negative free texts on patient reports revealed 15 post
      colonoscopy hospital admissions due to adverse events that had not been
      registered in the colonoscopy report. This increased the number of hospital
      admissions caused by adverse events from 3 (0.03 %) to 18 (0.16 %). In addition,
      there were 14 patient reports of severe events without hospital admission.
      Therefore, a total of 29 severe adverse events reported by patients were missed
      by conventional documentation in the colonoscopy form. Conclusion It is feasible
      to implement patient feedback as routine reporting to capture the full picture of
      colonoscopy-related adverse events. Some patients experience significant
      complications that are not recorded through any registries. Patient feedback
      forms should be tailored to capture adverse events after colonoscopy that are
      otherwise not easily disclosed.

PMID- 28445904
TI  - [Are there Sex Differences Regarding Ski Length to Height Ratio, Ski Length to
      Weight Ratio, Sidecut Radius and Ski Boot Sole Abrasion among ACL Injured Male
      and Female Skiers?]
AB  - Introduction Female skiers suffer from knee injuries twice as much as male
      skiers, and the risk of an injury to the anterior cruciate ligament (ACL) is
      three times greater among females compared to males. The sex-specific ACL injury
      risk depends on internal (e. g. age, skiing skills, fitness level) and external
      (e. g. slope and weather conditions, ski equipment) factors. However, it is not
      clear whether male and female recreational skiers with an ACL injury differ
      regarding the sidecut radius and ski boot sole abrasion. Method This
      questionnaire-based study was conducted in the winter seasons 2014/15 and
      2015/16. During those periods, data of ACL-injured skiers were collected at an
      Austrian ski clinic. The questionnaire included information about demographics,
      skiing skills, type of fall, binding release, and injury diagnosis. Furthermore,
      the ski length and sidecut radius were notated from the ski, and abrasion of ski
      boot sole was measured at the toe and heel piece of the ski boot using a caliper.
      Results In total 164 ACL-injured skiers (67 % females) with a mean age of 41.7 +/
      11.5 years were recorded. Males used significantly longer skies compared to
      females (168.3 +/- 6.6 vs. 157.5 +/- 5.9 cm, p < 0.001), however the ski length
      to height ratio (94.0 +/- 3.4 vs. 94.1 +/- 3.3 %) showed no significant
      difference between the two sexes. The ski length to weight ratio was
      significantly different between females and males (2.5 +/- 0.3 vs. 2.0 +/- 0.2
      cm/kg). The sidecut radius (13.5 +/- 1.4 vs. 15.6 +/- 2.6 m, p < 0.001) was
      significantly lower among ACL-injured females compared to ACL-injured males. No
      sex-specific differences were found regarding the abrasion of ski boot soles,
      neither at the toe piece (5.4 +/- 1.2 vs. 5.5 +/- 1.1 mm) nor at the heel piece
      (6.0 +/- 1.7 vs. 6.0 +/- 1.6 mm) between females and males. For both sexes the
      most common type of fall was the forward fall with body rotation (approximately
      59 %). Failure of binding release was significantly more often reported by
      females compared to males (86 vs. 44 %, p < 0.001). Conclusion Female and male
      skiers with an ACL injury differ regarding the sidecut radius, the ski length to
      weight ratio, and the proportion of failure of binding release. Moreover,
      although no sex-specific differences were found regarding the abrasion of ski
      boot soles, the mean ski boot abrasion was beyond the ISO standard tolerances.

PMID- 28445905
TI  - Prenatal Diagnosis of Galen Vein Aneurysm Using Ultrasonography and Magnetic
      Resonance Imaging and Perinatal and Long-Term Neurological Outcomes: A Case
      Series.
AB  - Objective To describe the prenatal diagnosis of Galen vein aneurysm (GVA) based
      on ultrasonography and magnetic resonance imaging (MRI) in a series of cases, as
      well as its postnatal outcomes and follow-up until 4 years of age. Methods A
      retrospective longitudinal study was performed, analyzing a database comprising
      seven cases of prenatal diagnosis of GVA at two Brazilian institutions from
      February of 2000 to May of 2012. The following data were evaluated: gestational
      age at diagnosis, GVA dimensions on ultrasonography, associated fetal changes,
      findings on fetal echocardiography, gestational age at delivery, type of
      delivery, birth weight, Apgar score at the 1st and 5th minutes, neonatal
      outcomes, and survival with follow-up until 4 years of age. Results The mean
      gestational age +/- standard deviation on the prenatal diagnosis of GVA based on
      ultrasonography was 25 +/- 4.9 weeks. The mean length of GVA was 3.2 +/- 0.4 cm.
      The mean gestational age at birth was 37.5 +/- 0.7 weeks, and a cesarean section
      was performed in 85.7% of the cases (6/7). The mean birth weight was 3,070 +/-
      240.4 g. The total survival rate was 42.8% (4/7), with three neonatal deaths. Of
      the four survivors, three presented with normal neuropsychomotor development
      until 4 years of age and only one showed serious neurological sequelae.
      Ultrasonography and MRI showed similar findings for all seven cases. Conclusions
      Galen Vein Aneurysm is associated with a high neonatal death rate. Therefore, its
      prenatal diagnosis is essential for parent counseling and follow-up at tertiary
      care institutions.

PMID- 28445906
TI  - [Bipolar stimulation may improve the efficacy of the percutaneous nerve
      evaluation test of sacral neuromodulation].
AB  - Purpose This study evaluates the hypothesis that bipolar stimulation of the S3
      and S4 sacral roots may enhance the efficacy of the percutaneous nerve evaluation
      (PNE) test. Material and Methods In this case-control-study, we enrolled 43
      patients undergoing bipolar PNE and 57 controls undergoing unipolar PNE. For
      bipolar PNE, four test electrodes were placed at the bilateral S3 and S4 roots.
      The electrodes at the S3 and S4 roots of each side were connected to obtain
      bipolar stimulation. The test protocol over eight days included unilateral and
      bilateral stimulation of the S3 and S4 sacral roots. Eight days after
      implantation, the electrodes were removed and test results from bladder diaries
      were collected. Results The unipolar test procedure was successful in 47 %
      (27/57) of cases. The bipolar test procedure was successful in 58 % (25/43). In
      the bipolar group, 63 % (12/19) of patients with neurogenic tract dysfunction
      profited from treatment, vs. 57 % (13/23) in the unipolar group. Patients without
      a neurologic disease had a successful test in 58 % (14/24) of cases treated with
      bipolar PNE vs. 41 % (14/24) treated with unipolar PNE. Multivariate analysis did
      not reveal a statistically significant difference between groups. Conclusion
      Although not significant in this population, bipolar PNE may improve efficacy
      compared to the unipolar test procedure. Similar observations were made in
      subgroups of neurogenic and non-neurogenic bladder dysfunctions.

PMID- 28445907
TI  - [Not Available].

PMID- 28445908
TI  - Diagnosis of Pulmonary Artery Embolism: Comparison of Single-Source CT and 3rd
      Generation Dual-Source CT using a Dual-Energy Protocol Regarding Image Quality
      and Radiation Dose.
AB  - Purpose To compare radiation dose, subjective and objective image quality of 3 rd
      generation dual-source CT (DSCT) and dual-energy CT (DECT) with conventional 64
      slice single-source CT (SSCT) for pulmonary CTA. Materials and Methods 180
      pulmonary CTA studies were performed in three patient cohorts of 60 patients
      each. Group 1: conventional SSCT 120 kV (ref.); group 2: single-energy DSCT 100
      kV (ref.); group 3: DECT 90/Sn150 kV. CTDIvol, DLP, effective radiation dose were
      reported, and CT attenuation (HU) was measured on three central and peripheral
      levels. The signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR) were
      calculated. Two readers assessed subjective image quality according to a five
      point scale. Results Mean CTDIvol and DLP were significantly lower in the dual
      energy group compared to the SSCT group (p < 0.001 [CTDIvol]; p < 0.001 [DLP])
      and the DSCT group (p = 0.003 [CTDIvol]; p = 0.003 [DLP]), respectively. The
      effective dose in the DECT group was 2.79 +/- 0.95 mSv and significantly smaller
      than in the SSCT group (4.60 +/- 1.68 mSv, p < 0.001) and the DSCT group (4.24 +/
      2.69 mSv, p = 0.003). The SNR and CNR were significantly higher in the DSCT
      group (p < 0.001). Subjective image quality did not differ significantly among
      the three protocols and was rated good to excellent in 75 % (135/180) of cases
      with an inter-observer agreement of 80 %. Conclusion Dual-energy pulmonary CTA
      protocols of 3 rd generation dual-source scanners allow for significant reduction
      of radiation dose while providing excellent image quality and potential
      additional information by means of perfusion maps. Key Points: . Dual-energy CT
      with 90/Sn150 kV configuration allows for significant dose reduction in pulmonary
      CTA.. . Subjective image quality was similar among the three evaluated CT
      protocols (64-slice SSCT, single-energy DSCT, 90/Sn150 kV DECT) and was rated
      good to excellent in 75% of cases.. . Dual-energy CT provides potential
      additional information by means of iodine distribution maps.. Citation Format .
      Petritsch B, Kosmala A, Gassenmaier T et al. Diagnosis of Pulmonary Artery
      Embolism: Comparison of Single-Source CT and 3rd Generation Dual-Source CT using
      a Dual-Energy Protocol Regarding Image Quality and Radiation Dose. Fortschr
      Rontgenstr 2017; 189: 527 - 536.

PMID- 28445909
TI  - Transient Severe Motion Artifact Related to Gadoxetate Disodium-Enhanced Liver
      MRI: Frequency and Risk Evaluation at a German Institution.
AB  - Purpose Varying frequencies (5 - 18 %) of contrast-related transient severe
      motion (TSM) imaging artifacts during gadoxetate disodium-enhanced arterial phase
      liver MRI have been reported. Since previous reports originated from the United
      States and Japan, we aimed to determine the frequency of TSM at a German
      institution and to correlate it with potential risk factors and previously
      published results. Materials and Methods Two age- and sex-matched groups were
      retrospectively selected (gadoxetate disodium n = 89; gadobenate dimeglumine n =
      89) from dynamic contrast-enhanced MRI examinations in a single center.
      Respiratory motion-related artifacts in non-enhanced and dynamic phases were
      assessed independently by two readers blinded to contrast agents on a 4-point
      scale. Scores of >= 3 were considered as severe motion artifacts. Severe motion
      artifacts in arterial phases were considered as TSM if scores in all other phases
      were < 3. Potential risk factors for TSM were evaluated via logistic regression
      analysis. Results For gadoxetate disodium, the mean score for respiratory motion
      artifacts was significantly higher in the arterial phase (2.2 +/- 0.9) compared
      to all other phases (1.6 +/- 0.7) (p < 0.05). The frequency of TSM was
      significantly higher with gadoxetate disodium (n = 19; 21.1 %) than with
      gadobenate dimeglumine (n = 1; 1.1 %) (p < 0.001). The frequency of TSM at our
      institution is similar to some, but not all previously published findings.
      Logistic regression analysis did not show any significant correlation between TSM
      and risk factors (all p > 0.05). Conclusion We revealed a high frequency of TSM
      after injection of gadoxetate disodium at a German institution, substantiating
      the importance of a diagnosis-limiting phenomenon that so far has only been
      reported from the United States and Japan. In accordance with previous studies,
      we did not identify associated risk factors for TSM. Key Points:  . Gadoxetate
      disodium causes TSM in a relevant number of patients.. . The frequency of TSM is
      similar between the USA, Japan and Germany.. . To date, no validated risk factors
      for TSM could be identified.. Citation Format . Well L, Rausch VH, Adam G et al.
      Transient Severe Motion Artifact Related to Gadoxetate Disodium-Enhanced Liver
      MRI: Frequency and Risk Evaluation at a German Institution. Fortschr Rontgenstr
      2017; 189: 651 - 660.

PMID- 28445910
TI  - Influence of Contrast Media on Bone Mineral Density (BMD) Measurements from
      Routine Contrast-Enhanced MDCT Datasets using a Phantom-less BMD Measurement
      Tool.
AB  - Aim To evaluate the differences in phantom-less bone mineral density (BMD)
      measurements in contrast-enhanced routine MDCT scans at different contrast
      phases, and to develop an algorithm for calculating a reliable BMD value.
      Materials and Methods 112 postmenopausal women from the age of 40 to 77 years
      (mean age: 57.31 years; SD 9.61) who underwent a clinically indicated MDCT scan,
      consisting of an unenhanced, an arterial, and a venous phase, were included. A
      retrospective analysis of the BMD values of the Th12 to L4 vertebrae in each
      phase was performed using a commercially available phantom-less measurement tool.
      Results The mean BMD value in the unenhanced MDCT scans was 79.76 mg/cm3 (SD
      31.20), in the arterial phase it was 85.09 mg/cm3 (SD 31.61), and in the venous
      phase it was 86.18 mg/cm3 (SD 31.30). A significant difference (p < 0.001) was
      found between BMD values on unenhanced and contrast-enhanced MDCT scans. There
      was no significant difference between BMD values in the arterial and venous
      phases (p = 0.228). The following conversion formulas were calculated using
      linear regression: unenhanced BMD = -2.287 + 0.964 * [arterial BMD value] and 
      4.517 + 0.978 * [venous BMD value]. The intrarater agreement of BMD measurements
      was calculated with an intraclass correlation (ICC) of 0.984 and the
      interobserver reliability was calculated with an ICC of 0.991. Conclusion Phantom
      less BMD measurements in contrast-enhanced MDCT scans result in increased mean
      BMD values, but, with the formulas applied in our study, a reliable BMD value can
      be calculated. However, the mean BMD values did not differ significantly between
      the arterial and venous phases. Key points  . BMD can be assessed on routine CT
      scans using a phantom-less tool.. . i. v. contrast agent significantly elevates
      BMD values measured on routine CT scans.. . BMD values measured in the arterial
      and venous phase did not differ significantly.. . Conversion formulas were
      defined for the calculation of a reliable BMD.. . The phantom-less tool showed
      good reliability and is a promising method.. Citation Format . Toelly A, Bardach
      C, Weber M et al. Influence of Contrast Media on Bone Mineral Density (BMD)
      Measurements from Routine Contrast-Enhanced MDCT Datasets using a Phantom-less
      BMD Measurement Tool. Fortschr Rontgenstr 2017; 189: 537 - 543.

PMID- 28445911
TI  - ?

PMID- 28445912
TI  - ?

PMID- 28445913
TI  - ?

PMID- 28445914
TI  - Clinical Significance of Intraluminal Contrast Enhancement in Patients with
      Spontaneous Cervical Artery Dissection: A Black-Blood MRI Study.
AB  - Purpose Recent studies have suggested that intraluminal thrombi show contrast
      enhancement on carotid black-blood T1w MRI. The aim of this study was to evaluate
      the significance of intraluminal contrast enhancement (iCE) regarding symptom
      status in patients with spontaneous cervical artery dissection (sCAD). Methods 33
      consecutive patients (19 men) with sCAD received a brain MRI (DIFF, T2w, T2*w,
      FLAIR) and a multi-sequence 3T-MRI with fat-saturated high-resolution black-blood
      T1w-sequences pre- and post-contrast, contrast-enhanced MR angiography and TOF
      images of carotid and vertebral arteries. Presence/absence of iCE, vessel
      occlusion and vessel wall hematoma (hyperintense in T1w pre-contrast) were
      analysed by two radiologists in consensus decision. Results 44 of 132 analysed
      vessels had a vessel wall hematoma, consistent with sCAD. In 17 of 44 dissected
      vessels an acute ischemic stroke was found. 16 of 17 (94.1 %) vessels ipsilateral
      to ischemic stroke demonstrated iCE, compared to 9 of 44 (20.4 %) dissected
      vessels without stroke (P< 0.001). The presence/absence of iCE resulted in a
      sensitivity, specificity, positive and negative predictive value and accuracy for
      ischemic stroke of 0.94, 0.67, 0.64, 0.95, and 0.77, respectively, and an odds
      ratio of 32.0. Conclusion iCE, which is suggestive of intraluminal thrombus
      formation, is strongly correlated with ischemic symptoms in patients with sCAD.
      Key points  . Intraluminal contrast enhancement is associated with cerebral
      ischemia in corresponding vessel territories in patients with cervical artery
      dissection.. . Our results suggest that intraluminal contrast enhancement
      represents intraluminal thrombus formation.. . Black-blood imaging might be
      useful to identify those patients with cervical artery dissection at higher risk
      for initial or recurrent stroke.. Citation Format . Coppenrath E, Lenz O, Sommer
      N et al. Clinical Significance of Intraluminal Contrast Enhancement in Patients
      with Spontaneous Cervical Artery Dissection: A Black-Blood MRI Study. Fortschr
      Rontgenstr 2017; 189: 624 - 631.

PMID- 28445915
TI  - Effect of Low-Dose Aspirin on the Time of Onset of Preeclampsia and Time of
      Delivery.

PMID- 28445916
TI  - Brain regions essential for word comprehension: Drawing inferences from patients.

PMID- 28445917
TI  - Should mentoring be mandatory for trainees? No.

PMID- 28445918
TI  - Should mentoring be mandatory for trainees? Yes.

PMID- 28445919
TI  - Making a difference: Pragmatic paediatric pain management.

PMID- 28445920
TI  - Endobronchial ultrasound elastography for the differentiation of benign and
      malignant lymph nodes - Reply.

PMID- 28445921
TI  - Assessment of the synergic effect of immunomodulation on nerve repair using
      multiparametric magnetic resonance imaging.
AB  - INTRODUCTION: The immune system plays a pivotal role in nerve injury. The aim of
      this study was to determine the role of multiparametric magnetic resonance
      imaging (MRI) in evaluation of the synergic effect of immunomodulation on nerve
      regeneration in neurotmesis. METHODS: Rats with sciatic nerve neurotmesis and
      surgical repair underwent serial multiparametric MR examinations over an 8-week
      period after subepineurial microinjection of lipopolysaccharide (LPS) and
      subsequent subcutaneous injection of FK506 or subepineurial microinjection of LPS
      or phosphate-buffered saline (PBS) alone. RESULTS: Nerves treated with
      immunomodulation showed more prominent regeneration than those treated with LPS
      or PBS alone and more rapid restoration toward normal T2, fractional anisotropy
      (FA), and radial diffusivity (RD) values than nerves injected with LPS or PBS.
      DISCUSSION: Nerves treated with immunomodulation exert synergic beneficial
      effects on nerve regeneration that can be predicted by T2 measurements and FA and
      RD values. Muscle Nerve 57: E38-E45, 2018.

PMID- 28445922
TI  - The canaries in the coal mine: mune and munix in amyotrophic lateral sclerosis.

PMID- 28445923
TI  - How to get the most out of your mentor.

PMID- 28445924
TI  - Optometrists' scope of practice.

PMID- 28445925
TI  - Endobronchial ultrasound elastography for the differentiation of benign and
      malignant lymph nodes.

PMID- 28445928
TI  - Regulation of angiogenic behaviors by oxytocin receptor through Gli1-indcued
      transcription of HIF-1alpha in human umbilical vein endothelial cells.
AB  - Angiogenesis is a dynamic hypoxia-stimulated process playing a key role in tissue
      growth and repair under various pathophysiological circumstances. Abnormal
      angiogenesis contributes to the pathogenesis of many human diseases. Oxytocin
      receptor is a classical G-protein-coupled receptor expressed on endothelial
      cells. The present study was aimed to investigate how oxytocin receptor regulated
      the angiogenic behaviors of human umbilical vein endothelial cells (HUVECs). We
      found that oxytocin at 0.1MUM significantly increased cell proliferation,
      upregulated the mRNA and protein expression of CD31 and vWF (two important
      endothelial markers), and enhanced the tuber formation capacity in HUVECs.
      However, oxytocin receptor inhibitor atosiban at 10MUM significantly suppressed
      these angiogenic properties of HUVECs. Additionally, hypoxia-inducible factor
      1alpha (HIF-1alpha) inhibitor PX-478 at 20MUM also remarkably inhibited the
      angiogenic properties of HUVECs. We further found that atosiban at 10MUM
      significantly repressed the promoter activity of HIF-1alpha and reduced the mRNA
      and protein expression of HIF-1alpha in HUVECs. Moreover, pharmacological
      inhibition of HIF-1alpha by PX-478 at 20MUM abolished oxytocin-enhanced
      angiogenic properties of HUVECs. Finally, transcription factor Gli1 inhibitor
      GANT-58 at 5MUM significantly abolished oxytocin-induced mRNA and protein
      expression of HIF-1alpha, while the nuclear abundance of Gli1 was significantly
      reduced by atosiban at 10MUM, but was increased by oxytocin at 0.1MUM in HUVECs.
      GANT-58 at 5MUM also significantly abolished oxytocin-enhanced angiogenic
      properties of HUVECs. Altogether, these discoveries suggested that oxytocin
      receptor signaling promoted the angiogenic behaviors of HUVECs via Gli1-indcued
      transcription of HIF-1alpha. We provided novel molecular insights into
      endothelial cell-mediated angiogenesis.

PMID- 28445927
TI  - Vaccines targeting preS1 domain overcome immune tolerance in hepatitis B virus
      carrier mice.
AB  - : Strong tolerance to hepatitis B virus (HBV) surface antigens limits the
      therapeutic effect of the conventional hepatitis B surface antigen (HBsAg)
      vaccination in both preclinical animal models and patients with chronic hepatitis
      B (CHB) infection. In contrast, we observed that clinical CHB patients presented
      less immune tolerance to the preS1 domain of HBV large surface antigen. To study
      whether targeting the weak tolerance of the preS1 region could improve therapy
      gain, we explored vaccination with the long peptide of preS1 domain for HBV
      virions clearance. Our study showed that this preS1-polypeptide rather than HBsAg
      vaccination induced robust immune responses in HBV carrier mice. The anti-preS1
      rapidly cleared HBV virions in vivo and blocked HBV infection to hepatocytes in
      vitro. Intriguingly, vaccination of preS1-polypeptide even reduced the tolerized
      status of HBsAg, opening a therapeutic window for the host to respond to the
      HBsAg vaccine. A sequential administration of antigenically distinct preS1
      polypeptide and HBsAg vaccines in HBV carrier mice could finally induce
      HBsAg/hepatitis B surface antibody serological conversion and clear chronic HBV
      infection in carrier mice. CONCLUSION: These results suggest that preS1 can
      function as a therapeutic vaccine for the control of CHB. (Hepatology
      2017;66:1067-1082).

PMID- 28445926
TI  - Emerging Treatment Models in Rheumatology: Antiphospholipid Syndrome and
      Pregnancy: Pathogenesis to Translation.

PMID- 28445929
TI  - The kinesin motor protein Kif7 is required for T-cell development and normal MHC
      expression on thymic epithelial cells (TEC) in the thymus.
AB  - Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway
      activation through influencing structure of the primary cilium. Here we show that
      Kif7 is required for normal T-cell development, despite the fact that T-cells
      lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency
      increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but
      reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition
      from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the
      CD8 lineage. Expression of CD5, which correlates with TCR signal strength, was
      reduced on DP and mature CD4 and CD8 cells, as a result of thymocyte-intrinsic
      Kif7-deficiency, and Kif7-deficient T-cells from radiation chimeras activated
      less efficiently when stimulated with anti-CD3 and anti-CD28 in vitro. Kif7
      deficient thymocytes showed higher expression of the Hedgehog target gene Ptch1
      than WT, but were less sensitive to treatment with recombinant Shh, and Kif7
      deficient T-cell development was refractory to neutralisation of endogenous Hh
      proteins, indicating that Kif7-deficient thymocytes were unable to interpret
      changes in the Hedgehog signal. In addition, Kif7-deficiency reduced cell-surface
      MHCII expression on thymic epithelial cells.

PMID- 28445930
TI  - Opioids: Modulators of angiogenesis in wound healing and cancer.
AB  - Opioids are potent drugs that are widely used to control wound or cancer pain.
      Increasing evidence suggest that opioids mediate clinically relevant effects that
      go beyond their classical role as analgesics. Of note, opioids appear to modulate
      angiogenesis - a process that is critical in wound healing and cancer
      progression. In this review, we focus on pro- and anti-angiogenic facets of
      opioids that arise from the activation of individual opioid receptors and the
      usage of individual concentrations or application routes. We overview the still
      incompletely elucidated mechanisms of these angiogenic opioid actions. Moreover,
      we describe plausible opioids effects, which - although not primarily studied in
      the context of vessel formation - may be related to the opioid-driven processes
      of angiogenesis. Finally we discuss the use of opioids as an innovative
      therapeutic avenue for the treatment of chronic wounds and cancer.

PMID- 28445931
TI  - High glucose induces apoptosis via upregulation of Bim expression in proximal
      tubule epithelial cells.
AB  - Diabetic nephropathy is the primary cause of end-stage renal disease. Apoptosis
      of tubule epithelial cells is a major feature of diabetic nephropathy. The
      mechanisms of high glucose (HG) induced apoptosis are not fully understood. Here
      we demonstrated that, HG induced apoptosis via upregulating the expression of
      proapoptotic Bcl-2 homology domain 3 (BH3)-only protein Bim protein, but not
      bring a significant change in the baseline level of autophagy in HK2 cells. The
      increase of Bim expression was caused by the ugregulation of transcription
      factors, FOXO1 and FOXO3a. Bim expression initiates BAX/BAK-mediated mitochondria
      dependent apoptosis. Silence of Bim by siRNA in HK2 cells prevented HG-induced
      apoptosis and also sensitized HK2 cells to autophagy during HG treatment. The
      autophagy inhibitor 3-MA increased the injury in Bim knockdown HK2 cells by
      retriggering apoptosis. The above results suggest a Bim-independent apoptosis
      pathway in HK2 cells, which normally could be inhibited by autophagy. Overall,
      our results indicate that HG induces apoptosis via up-regulation of Bim
      expression in proximal tubule epithelial cells.

PMID- 28445932
TI  - High CFTR expression in Philadelphia chromosome-positive acute leukemia protects
      and maintains continuous activation of BCR-ABL and related signaling pathways in
      combination with PP2A.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an
      anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ
      domain, CFTR is capable of regulating other proteins, such as protein phosphatase
      2A (PP2A). The aberrant expression and mutation of CFTR have been observed in
      several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia,
      including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic
      myelogenous leukemia blast crisis phases (CML-BC). In this study, we demonstrated
      the mean expression level of CFTR in Ph+ acute leukemia cells was markedly higher
      than that in Ph- B-ALL and CML-chronic phase cells. CFTRinh-172, a classic CFTR
      inhibitor, down-regulated the expression of CFTR, p-BCR-ABL and classical
      Wnt/beta-catenin signaling in Ph+ acute leukemia cells, while imatinib had no
      effect on CFTR. Importantly, reduced efficacy of CFTRinh-172 was closely
      associated with elevated PP2A phosphatase activity. Furthermore, we confirmed an
      interaction between CFTR and the PP2AA subunit in K562 cells. In addition, we
      demonstrated CFTR and PP2AA interact in the cytosol, resulting in PP2A complex
      inactivation and increased degradation of PP2A substrates via the
      lysosomal/proteasome pathway. In conclusion, our results showed CFTR was highly
      expressed in Ph+ acute leukemia, which protected and maintained the continuous
      activation of BCR-ABL and the canonical Wnt/beta-catenin signaling pathway by
      decreasing PP2A phosphatase activity. According to this working model of the CFTR
      PP2A-BCR-ABL axis, targeting the CFTR protein will activate PP2A and may offer a
      new treatment strategy for Ph+ acute leukemia, especially for patients exhibiting
      high levels of CFTR expression.

PMID- 28445933
TI  - The long noncoding RNA HOTAIR promotes Parkinson's disease by upregulating LRRK2
      expression.
AB  - Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that
      regulate cellular processes. HOTAIR (Hox transcript antisense intergenic RNA), an
      approximately 2.2 kb long noncoding RNA transcribed from the HOXC locus, is
      upregulated in various diseases. However, the role of HOTAIR in Parkinson's
      disease (PD) remains unclear. A mouse model of PD was developed by
      intraperitoneal injection of MPTP. The expression of HOTAIR and LRRK2 were
      detected in the PD mice and in human neuroblastoma cell lines SH-SY5Y pretreated
      with MPP+. The effect of HOTAIR on the expression of LRRK2 was examined in SH
      SY5Y cells through overexpressing or knockdown of HOTAIR. MTT and flow cytometry
      assay were performed to measure the cell viability and apoptosis of SH-SY5Y
      cells. We found that HOTAIR was up-regulated in midbrain tissue of MTPT induced
      PD mice and in SH-SY5Y cells exposed to MPP+. With the presence of HOTAIR
      overexpression in SH-SY5Y cells, the expression of LRRK2 was increased compared
      with that in the control. HOTAIR knockdown showed a protective effect on the cell
      viability of SH-SY5Y cells pretreated with MPP+. HOTAIR knockdown provided
      protection against MPP+-induced DA neuronal apoptosis by repressing caspase 3
      activity. The finding that HOTAIR promoted PD induced by MPTP could add our
      understanding of the molecular mechanisms in PD. These findings suggested that
      inhibition of HOTAIR levels is an effective disease-modifying strategy in PD.

PMID- 28445934
TI  - Jarid2 is essential for the maintenance of tumor initiating cells in bladder
      cancer.
AB  - Bladder cancer is the most common urologic malignancy in China, with an increase
      of the incidence and mortality rates over past decades. Recent studies suggest
      that bladder tumors are maintained by a rare fraction of cells with stem cell
      proprieties. Targeting these bladder tumor initiating cell (TICs) population can
      overcome the drug-resistance of bladder cancer. However, the molecular and
      genetic mechanisms regulating TICs in bladder cancer remain poorly defined.
      Jarid2 is implicated in signaling pathways regulating cancer cell epithelial
      mesenchymal transition, and stem cell maintenance. The goal of our study was to
      examine whether Jarid2 plays a role in the regulation of TICs in bladder cancer.
      We found that knockdown of Jarid2 was able to inhibit the invasive ability and
      sphere-forming capacity in bladder cancer cells. Moreover, knockdown of Jarid2
      reduced the proportion of TICs and impaired the tumorigenicity of bladder cancer
      TICs in vivo. Conversely, ectopic overexpression of Jarid2 promoted the invasive
      ability and sphere-forming capacity in bladder cancer cells. Mechanistically,
      reduced Jarid2 expression led to the upregulation of p16 and H3K27me3 level at
      p16 promoter region. Collectively, we provided evidence that Jarid2 via
      modulation of p16 is a putative novel therapeutic target for treating malignant
      bladder cancer.

PMID- 28445935
TI  - Inhibition of mTORC2 component RICTOR impairs tumor growth in pancreatic cancer
      models.
AB  - Mammalian Target of Rapamycin complex 2 (mTORC2) and its regulatory component
      Rapamycin-insensitive companion of mTOR (RICTOR) are increasingly recognized as
      important players in human cancer development and progression. However, the role
      of RICTOR in human pancreatic ductal adenocarcinoma (PDAC) is unclear so far.
      Here, we sought to analyze the effects of RICTOR inhibition in human pancreatic
      cancer cell lines in vitro and in vivo. Furthermore, RICTOR expression was
      determined in human PDAC samples. Results demonstrate that depletion of RICTOR
      with siRNA (transient knock-down) or shRNA (stable knock-down) has an inhibitory
      effect on tumor growth in vitro. Moreover, RICTOR inhibition led to impaired
      phosphorylation/activity of AGC kinases (AKT, SGK1). Interestingly, hypoxia
      induced expression of hypoxia-induced factor-1alpha (HIF-1alpha) was diminished
      and secretion of vascular-endothelial growth factor-A (VEGF-A) was impaired upon
      targeting RICTOR. Stable RICTOR knock-down led to significant inhibition of tumor
      growth in subcutaneous and orthotopic tumor models which was accompanied by
      significant reduction of tumor cell proliferation. Finally, immunohistochemical
      analyses of 85 human PDAC samples revealed significantly poorer survival in
      patients with higher RICTOR expression. In conclusion, these findings provide
      first evidence for mTORC2/RICTOR as an attractive novel target for treatment of
      human PDAC.

PMID- 28445936
TI  - Increased expression of ZEB1-AS1 correlates with higher histopathological grade
      and promotes tumorigenesis in bladder cancer.
AB  - Bladder cancer is one of the most common urinary cancers worldwide. Emerging
      studies indicated that long non-coding RNAs (lncRNAs) play crucial roles in
      cancer biology. In this study, we found that a novel lncRNA Zinc finger E-box
      binding homeebox1 (ZEB1) antisense RNA (ZEB1-AS1) was overexpressed in bladder
      cancer tissues compared to paired noncancerous tissues. Moreover, the expression
      of ZEB1-AS1 was positive correlated with higher histological grade and TNM stage
      in bladder cancer. Furthermore, Loss-of-function experiments showed that down
      regulation of ZEB1-AS1 not only can suppress cell growth but also can inhibit
      migration and induce apoptosis in bladder cancer cell lines 5637 and SW780. In
      conclusion, these findings indicated that ZEB1-AS1 plays regulatory roles in
      bladder cancer and it may become a novel molecular biomarker of prognosis and
      therapy in bladder cancer.

PMID- 28445937
TI  - Methylation-mediated silencing of microRNA-211 promotes cell growth and
      epithelial to mesenchymal transition through activation of the AKT/beta-catenin
      pathway in GBM.
AB  - Aberrant expression of miR-211 has frequently been reported in cancer studies;
      however, its role in glioblastoma multiforme (GBM) has not been examined in
      detail. We investigated the function and the underlying mechanism of miR-211 in
      GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines.
      Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and
      in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed
      when miR-211 expression was restored. HMGA2 was identified as a down-stream
      target of miR-211. MiR-211 had an inhibitory effect on AKT/beta-catenin
      signaling, which was reversed by HMGA2 overexpression or miR-211 restoration. In
      addition, miR-211 was transcriptionally repressed by EZH2-induced H3K27
      trimethylation and promoter methylation. Overall, our findings revealed miR-211
      as a tumor suppressor in GBM and mir-211 may be a potential therapeutic target
      for GBM patients.

PMID- 28445938
TI  - Pirfenidone normalizes the tumor microenvironment to improve chemotherapy.
AB  - Normalization of the tumor microenvironment by selectively targeting components
      of the tumor extracellular matrix has been recently proposed to have the
      potential to decompress tumor blood vessels, increase vessel perfusion and thus,
      improve drug delivery and the efficacy of cancer therapy. Therefore, we now need
      to identify safe and well tolerated pharmaceutical agents that are able to
      remodel the microenvironment of solid tumors and enhance chemotherapy. In this
      study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for
      the treatment of idiopathic pulmonary fibrosis, to investigate its possible role
      on tumor microenvironment normalization. Using two orthotopic mammary tumor
      models we demonstrate that Pirfenidone reduces collagen and hyaluronan levels
      and, as a result, significantly increases blood vessel functionality and
      perfusion and improves the anti-tumor efficacy of doxorubicin. Reduction of
      extracellular matrix components were mediated via TGFbeta signaling pathway
      inhibition due to downregulation of TGFbeta1, COL1A1, COL3A1, HAS2, HAS3
      expression levels. Our findings provide evidence that repurposing Pirfenidone
      could be used as a promising strategy to enhance drug delivery to solid tumors by
      normalizing the tumor microenvironment.

PMID- 28445939
TI  - Epigenetic therapy with inhibitors of histone methylation suppresses DNA damage
      signaling and increases glioma cell radiosensitivity.
AB  - Radiation therapy is widely used to treat human malignancies, but many tumor
      types, including gliomas, exhibit significant radioresistance. Radiation therapy
      creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid
      changes in epigenetic modifications, including increased histone methylation.
      This increased histone methylation recruits DNA repair proteins which can then
      alter the local chromatin structure and promote repair. Consequently, combining
      inhibitors of specific histone methyltransferases with radiation therapy may
      increase tumor radiosensitivity, particularly in tumors with significant
      therapeutic resistance. Here, we demonstrate that inhibitors of the H4K20
      methyltransferase SETD8 (UNC-0379) and the H3K9 methyltransferase G9a (BIX-01294)
      are effective radiosensitizers of human glioma cells. UNC-0379 blocked H4K20
      methylation and reduced recruitment of the 53BP1 protein to DSBs, although this
      loss of 53BP1 caused only limited changes in radiosensitivity. In contrast, loss
      of H3K9 methylation through G9a inhibition with BIX-01294 increased
      radiosensitivity of a panel of glioma cells (SER2Gy range: 1.5 - 2.9). Further,
      loss of H3K9 methylation reduced DSB signaling dependent on H3K9, including
      reduced activation of the Tip60 acetyltransferase, loss of ATM signaling and
      reduced phosphorylation of the KAP-1 repressor. In addition, BIX-0194 inhibited
      DSB repair through both the homologous recombination and nonhomologous end
      joining pathways. Inhibition of G9a and loss of H3K9 methylation is therefore an
      effective approach for increasing radiosensitivity of glioma cells. These results
      suggest that combining inhibitors of histone methyltransferases which are
      critical for DSB repair with radiation therapy may provide a new therapeutic
      route for sensitizing gliomas and other tumors to radiation therapy.

PMID- 28445940
TI  - Suppression of allograft rejection by CD8+CD122+PD-1+ Tregs is dictated by their
      Fas ligand-initiated killing of effector T cells versus Fas-mediated own
      apoptosis.
AB  - Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are
      regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We
      have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft
      rejection, but also are more potent in suppression than conventional CD4+CD25+
      Tregs. However, the mechanisms underlying their suppression of alloimmunity are
      not well understood. In an adoptive T-cell transfer model of mice lacking
      lymphocytes, we found that suppression of skin allograft rejection by
      CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as
      either lacking Fas ligand or blocking it with antibodies largely abolished their
      suppression of allograft rejection mediated by transferred T cells. Their
      suppression was also mostly reversed when effector T cells lacked Fas receptor.
      Indeed, these FasL+ Tregs induced T cell apoptosis in vitro in a Fas/FasL
      dependent manner. However, their suppression of T cell proliferation in vitro was
      dependent on IL-10, but not FasL expression. Furthermore, adoptive transfer of
      CD8+CD122+PD-1+ Tregs significantly extended allograft survival even in wild-type
      mice if Tregs lacked Fas receptor or if recipients received recombinant IL-15, as
      these two measures synergistically expanded adoptively-transferred Tregs in
      recipients. Thus, this study may have important implications for Treg therapies
      in clinical transplantation.

PMID- 28445941
TI  - Palliative radiotherapy for gastric cancer: a systematic review and meta
      analysis.
AB  - BACKGROUND/PURPOSE: To review the efficacy and toxicity of palliative
      radiotherapy (RT) for symptomatic locally advanced gastric cancer (GC) and to
      determine the optimal RT schedule for symptom palliation. METHODS: We searched
      MEDLINE and CENTRAL for eligible studies published from 1995 to 2015. Outcomes of
      interest were relief of bleeding, pain and obstruction. RESULTS: Seven non
      comparative observational studies were included. There were large variations in
      RT dose and fractionation. The pooled overall response rates for bleeding, pain
      and obstruction symptoms were 74%, 67% and 68% respectively. There was no
      difference in response rate of bleeding between regimens with high biological
      equivalent dose (BED) of >= 39Gy versus regimens with low BED<39Gy regimens (p
      value =0.39). Grade 3 to 4 toxicities occurred in up to 15% of patients for
      patients treated with RT alone and up to 25% of patients treated with
      chemoradiotherapy. Health-related quality of life (HRQL) outcomes were not
      reported. CONCLUSION: More than two-thirds of patients receiving RT would have a
      clinical benefit. Low BED regimens appear to be adequate for symptom palliation.
      Toxicity rates appear acceptable for patients treated with RT alone. The optimal
      dose fractionation regimen for symptom palliation remains unclear. Prospective
      studies to determine the effects of palliative gastric RT on HRQL outcomes are
      warranted.

PMID- 28445942
TI  - MMP-3 and MMP-8 single-nucleotide polymorphisms are related to alcohol-induced
      osteonecrosis of the femoral head in Chinese males.
AB  - Our study investigated the association between MMP-3 and MMP-8 single-nucleotide
      polymorphisms (SNPs) and alcohol-induced osteonecrosis of the femoral head (ONFH)
      in 695 Chinese males (299 cases and 396 control subjects). The minor allele of
      MMP-3 rs650108 was associated with a 0.78-fold decrease in alcohol-induced ONFH
      risk in the allelic model (95% CI = 0.63-0.97, P = 0.026). In the genetic model
      adjusted for age, rs650108 was associated with decreased risk of alcohol-induced
      ONFH in the dominant model (OR = 0.68, 95% CI = 0.49-0.95, P = 0.022) and log
      additive model (OR = 0.78, 95% CI = 0.63-0.98, P = 0.030); MMP-8 rs11225394 was
      associated with increased risk in the codominant model (OR = 1.72, 95% CI = 1.15
      2.58, P= 0.010), dominant model (OR = 1.67, 95% CI = 1.12-2.48, P = 0.012), over
      dominant model (OR = 1.73, 95% CI = 1.16-2.59, P = 0.007) and log-additive model
      (OR = 1.57, 95% CI= 1.07-2.32, P = 0.022); and MMP-8 rs2012390 was associated
      with decreased risk in the dominant model (OR = 0.72, 95% CI = 0.53-0.97, P =
      0.032) and log-additive model (OR = 0.77, 95% CI = 0.60-0.98, P = 0.035).
      Haplotype analysis showed that the CGATATGT sequence mediated decreased alcohol
      induced ONFH risk (OR = 0.75, 95% CI = 0.57-0.97, P = 0.029). Therefore, among
      Chinese males, MMP-3 rs650108 and MMP-8 rs2012390 decrease alcohol-induced ONFH
      risk and MMP-8 rs11225394 increases it. Further study is needed to validate our
      conclusion.

PMID- 28445943
TI  - A molecular inversion probe-based next-generation sequencing panel to detect
      germline mutations in Chinese early-onset colorectal cancer patients.
AB  - The currently known Mendelian colorectal cancer (CRC) predisposition syndromes
      account for ~5-10% of all CRC cases, and are caused by inherited germline
      mutations in single CRC predisposing genes. Using molecular inversion probes
      (MIPs), we designed a targeted next-generation sequencing panel to identify
      mutations in seven CRC predisposing genes: APC, MLH1, MSH2, MSH6, PMS2, MUTYH and
      NTHL1. From a consecutive series of 2,371 Chinese CRC patients, 140 familial and
      non-familial cases were selected that were diagnosed with CRC at or below the age
      of 35 years. Through MIP-based sequencing we identified pathogenic variants in
      six genes in 16 out of the 140 (11.4%) patients selected. In 10 patients, known
      pathogenic mutations in APC (five patients), MLH1 (three patients), or MSH2 (two
      patients) were identified. Three additional patients were found to carry novel,
      likely pathogenic truncating (n = 2) and missense (n = 1) mutations in the MSH2
      gene and a concomitant loss of expression of both the MSH2 and MSH6 proteins in
      their respective tumor tissues. From our data, we conclude that targeted MIP
      based sequencing is a reliable and cost-efficient approach to identify patients
      with a Mendelian CRC syndrome.

PMID- 28445944
TI  - Angiotensin-converting enzyme 2 overexpression protects against doxorubicin
      induced cardiomyopathy by multiple mechanisms in rats.
AB  - Angiotensin-converting enzyme 2 (ACE2) is considered a potential therapeutic
      target of the renin-angiotensin system (RAS) for the treatment of cardiovascular
      diseases. We aimed to explore the effects of ACE2 overexpression on doxorubicin
      induced cardiomyopathy in rats. Rats were randomly divided into treatment and
      control groups. The rats of treatment group were injected intraperitoneally with
      6 doses of doxorubicin (2.5 mg/kg) within a period of two weeks. Two weeks after
      the initial injection of doxorubicin, these rats were randomly divided into Mock,
      Ad-EGFP, Ad-ACE2, and Cilazapril groups. The rats of Ad-EGFP and Ad-ACE2 groups
      received intramyocardial injection of Ad-EGFP and Ad-ACE2, respectively. The rats
      of Cilazapril group received cilazapril (10 mg/kg/day) via intragastric
      intubation. Apoptosis, inflammation, oxidative stress, cardiac function, the
      extent of myocardial fibrosis, and levels of ACE2, ACE, angiotensin II (AngII),
      and angiotensin (1-7) were evaluated. Four weeks after ACE2 gene transfer, the Ad
      ACE2 group showed not only reduced apoptosis, inflammatory response, oxidative
      stress, left ventricular (LV) volume, extent of myocardial fibrosis and mortality
      of rats, but also increased LV ejection fraction and ACE2 expression level
      compared with the Mock and Ad-EGFP groups. ACE2 overexpression was superior to
      cilazapril in improving doxorubicin-induced cardiomyopathy. The putative
      mechanisms may involve activation of the AMPK and PI3K-AKT pathways, inhibition
      of the ERK pathway, decrease of TGF-beta1 expression, and interactions of
      shifting RAS components, such as decreased myocardium AngII levels, increased
      myocardium Ang (1-7) levels, and reduced ACE expression. Thus, ACE2 may be a
      novel therapeutic approach to prevent and treat doxorubicin-induced
      cardiomyopathy.

PMID- 28445945
TI  - Non-small cell lung cancer associated microRNA expression signature: integrated
      bioinformatics analysis, validation and clinical significance.
AB  - Recently, increasing studies of miRNA expression profiling has confirmed that
      miRNA plays an essential role in non-small cell lung cancer (NSCLC). However,
      inconsistent or discrepant results exist in these researches. In present study,
      we performed an integrative analysis of 32 miRNA profiling studies compared the
      differentially expressed miRNA between NSCLC tissue and non-cancerous lung tissue
      to identify candidate miRNAs associated with NSCLC. 7 upregulated and 10
      downregulated miRNAs were identified as miRNA integrated-signature using Robust
      Rank Aggregation (RRA) method. qRT-PCR demonstrated that miR-21-5p, miR-210, miR
      205-5p, miR-182-5p, miR-31-5p, miR-183-5p and miR-96-5p were up-regulated,
      whereas miR-126-3p, miR-30a-5p, miR-451a, miR-143-3p and miR-30d-5p were down
      regulated more than 2 folds in the NSCLC, which was further validated in Tumor
      Cancer Genome Atlas (TCGA) database. Receiver operating characteristic (ROC)
      curve analysis confirmed that 9 miRNAs had good predictive performance (AUC >
      0.9). Cox regression analysis revealed that miR-21-5p (hazard ratio [HR]: 1.616,
      95% CI: 1.114-2.342, p = 0.011) and miR-30d-5p (HR: 0.578, 95% CI: 0.400-0.835, p
      = 0.003) were independent prognostic factors in NSCLC for overall survival. The
      accumulative effects of the two miRNAs on the prognosis of NSCLC were further
      estimated. The results showed that patients with two positive markers had a worse
      prognosis than those with one or none positive marker. In conclusion, this study
      contributes to the comprehension of the role of miRNAs in NSCLC and provides a
      basis for further clinical application.

PMID- 28445946
TI  - Dose invasive apocrine adenocarcinoma has worse prognosis than invasive ductal
      carcinoma of breast: evidence from SEER database.
AB  - BACKGROUND: Invasive apocrine adenocarcinoma (AAC) of breast is a rare
      histopathological subtype of breast carcinomas. We aim to investigate the
      different characteristics and prognostic outcomes between AAC and invasive ductal
      carcinoma (IDC) of breast cancer. RESULTS: AAC patients presented with older
      ages, more aggressive behaviors, lower ER and PR proportions, higher HER2
      amplification rates and less application of breast-conserving therapy and
      adjuvant chemotherapy compared to IDC patients. Long-term OS and DSS were both
      worse in ACC patients (p = 0.006, p = 0.012 respectively) than in IDC patients by
      Kaplan-Meier analysis. However, no significant difference was detected in DSS (p
      = 0.181) and OS (p = 0.116) between the matched two histological subtypes.
      Further subgroup analysis indicated that AJCC stage, ER status, PR status and
      HER2 status may be principal confounders for AAC prognosis. MATERIALS AND
      METHODS: With accession to the Surveillance, Epidemiology and End Result (SEER)
      database, a total of 260,596 patients met the eligibility criteria.
      Clinicopathological characteristics were compared between groups using Chi-square
      test. Univariate and multivariate analyses were applied to evaluate the overall
      survival (OS) and disease-specific survival (DSS). Subgroup analyses summarized
      the hazard ratio (HR) of AAC versus IDC using a forest plot. CONCLUSIONS: AAC had
      unique clinicopathological characteristics and it tended to be a more aggressive
      type than IDC. However, the worse prognosis was diminished after matching for
      demographic and clinicopathological factors. Deeper insights into AAC are in need
      to contribute to individualized and tailored therapy, which thereby may improve
      clinical management and outcomes.

PMID- 28445947
TI  - Characteristics and comparison of colorectal cancer incidence in Beijing with
      other regions in the world.
AB  - BACKGROUND: Population-based epidemiologic studies about colorectal cancer are
      lacking in China. This study aims to provide a basis for colorectal cancer
      screening and prevention, through analysis and comparisons the characteristics of
      the trends in colorectal cancer incidence in Beijing and selected representative
      regions. RESULTS: The annual incidence rate in Beijing region increased
      significantly, from 9.40/100,000 in 1998 to 18.61/100,000 in 2012. The stratified
      rate showed that the incidence of distal colon adenocarcinoma increased
      substantially in men, especially in those aged > 75 years and residing in urban
      areas. Although the incidence rate in Beijing is still lower than in Shanghai,
      Jiashan, and Hong Kong in China, it is increasing rapidly. Further, the incidence
      rate in Beijing is lower than in New York, Oxford and Osaka, but higher than in
      Mumbai and Kyadondo. The incidence trend in Beijing is increasing especially in
      older groups, while in other regions such as New York, it is decreasing in these
      age groups. MATERIALS AND METHODS: Colorectal cancer incidence data were obtained
      from Beijing Cancer Registry and Cancer Incidence in Five Continents Plus
      database. All incidence rates were age-standardized according to Segi's world
      population. Incidence trends were characterized by calculating the annual percent
      changes using the Joinpoint Regression Program. CONCLUSIONS: Compared with other
      regions, Beijing has a medium level of colorectal cancer incidence, however, it
      is increasing significantly. There are obvious differences in the cancer subsite,
      sex and age distributions between Beijing and other regions. Prevention and
      screening of colorectal cancer in Beijing should be strengthened.

PMID- 28445948
TI  - Combined MEK and Pi3'-kinase inhibition reveals synergy in targeting thyroid
      cancer in vitro and in vivo.
AB  - Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a
      major treat since surgery combined with Iodine131 therapy is ineffective on them.
      Small-molecule inhibitors are presenting a new hope for patients, but often lead
      to drug resistance in many cancers. Based on the major mutations found in thyroid
      cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor
      in pre-clinical models. We used human thyroid cancer cell lines and genetically
      engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of
      both inhibitors separately or in combination in terms of proliferation and
      signaling in vitro; tumor burden, histology, cell death induction and tumor
      markers expression in vivo. The combination of MEK and Pi'3-kinase inhibition
      shows a synergistic effect in term of proliferation and apoptosis induction
      through Survivin down-regulation in vitro. We show for the first time the effects
      of the combination of a MEK inhibitor and Pi3'-kinase inhibitor in a genetically
      engineered mouse model of aggressively lethal thyroid cancer. In fine, the two
      drugs cooperate to promote tumor shrinkage by inducing a proliferation arrest and
      an elevation of apoptosis in vivo. Moreover, a phenotypic reversion is also
      observed with a partial restoration of normal thyroid marker transcription, and
      thyroid cancer marker expression reduction.In conclusion, combination therapy of
      MEK and Pi3'-kinase inhibition synergizes to target double mutant thyroid cancer
      in vitro and in vivo. This multidrug approach could readily be translated into
      clinical practice and bring new perspectives for the treatment of incurable
      thyroid carcinoma.

PMID- 28445949
TI  - LMP1+SLAMF1high cells are associated with drug resistance in Epstein-Barr virus
      positive Farage cells.
AB  - How Epstein-Barr virus (EBV) affects the clinical outcome of EBV-positive diffuse
      large B-cell lymphoma (DLBCL) remains largely unknown. The viral oncogene LMP1 is
      at the crux of tumorigenesis and cell survival. Therefore, we examined the
      association between LMP1high cells drug resistance. We first assessed SLAMF1 as a
      surrogate marker for LMP1high cells. LMP1 and its target gene CCL22 were highly
      expressed in SLAMF1high Farage cells. These cells survived longer following
      treatment with a combination of cyclophosphamide, doxorubicin, vincristine and
      prednisone (CHOP). Genes associated with interferon-alpha, allograft rejection,
      NF-kappaB and STAT3 were also overexpressed in the surviving Farage cells.
      Specifically, CHOP treatment increased IL10, LMP1 and pSTAT3 expression levels in
      a dose-dependent fashion. Addition of exogenous IL4 greatly increased the levels
      of LMP1 and pSTAT3, which rendered the Farage cells more resistant to CHOP by up
      regulating the anti-apoptotic genes BCL-XL and MCL1. The Farage cells were
      sensitive to Velcade and STAT3, 5, and 6 inhibitors. Inhibition of NF-kappaB and
      STAT3, in combination with CHOP, decreased LMP1 levels and effectively induced
      cell death in the Farage cells. We suggest that LMP1high cells are responsible
      for the poor drug response of EBV+ DLBCL and that perturbation of the NF-kappaB
      and STAT signaling pathways increases toxicity in these cells.

PMID- 28445950
TI  - The discovery of a novel compound with potent antitumor activity: virtual
      screening, synthesis, biological evaluation and preliminary mechanism study.
AB  - Farnesyltransferase has been regarded as a promising drug target against cancer
      as it is critical for membrane association of several signal transduction
      proteins. In this study, a novel farnesyltransferase inhibitor (IMB-1406) was
      identified through virtual screening. It exhibits stronger potency (IC50s: 6.92
      8.99 MUM) than Sunitinib against all of the tested cancer cell lines. Preliminary
      studies on mechanism reveal that IMB-1406 induces apoptosis in HepG2 cells by
      arresting the cell cycle at the S phase, altering anti- and pro-apoptotic
      proteins leading to mitochondrial dysfunction and activation of caspase-3. This
      anti-tumor effect is most probably related to the inhibition of
      farnesyltransferase as indicated by molecular docking. Overall, IMB-1406 is a
      novel lead compound with potent antitumor activity and deserves further
      structural modifications.

PMID- 28445951
TI  - PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma.
AB  - Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective
      therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint
      have shown encouraging results in solid and hematologic cancers in clinical
      trials. Response to these immunomodulators is correlated with PD-L1 expression.
      Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and
      perihilar (pCCA) cholangiocarcinomas, and to correlate our results with
      clinicopathological features, density of tumor-infiltrating lymphocytes (TILs)
      and PD-1 expression.A series of 58 iCCAs and 41 pCCAs was included in the study.
      PD-L1, PD-1 and CD3 expression was investigated using immunohistochemistry.
      Density of TILs was evaluated by immunohistochemistry using a quantitative score
      of CD3-stained intratumoral lymphocytes.PD-L1 expression by neoplastic cells was
      observed in 9 cases (9%, 5 iCCAs and 4 pCCAs). PD-L1 positive inflammatory cell
      aggregates were identified in 46% (n = 46) of the cases (31 iCCAs and 15 pCCAs).
      PD-L1 expression by either neoplastic or inflammatory cells was associated to
      high density of CD3-positive TILs (p = 0.01 and p = 0.005, respectively). The
      number of PD-L1 positive inflammatory cell aggregates was higher in tumors with
      high PD-1 expression (p < 0.0001).Altogether, PD-L1 in iCCA and pCCA is mainly
      expressed in tumors with high density of TILs. Our results suggest that CCAs with
      dense intratumoral lymphocytic infiltration might represent good candidates for
      PD-L1/PD-1 blocking agents.

PMID- 28445952
TI  - SOCS3 inhibits the pathological effects of IL-22 in non-melanoma skin tumor
      derived keratinocytes.
AB  - Basal cell carcinomas (BCC) and squamous-cell carcinomas (SCC) are common
      malignancies in humans, caused by neoplastic transformation of keratinocytes of
      the basal or suprabasal layers of epidermis, respectively. Tumor-infiltrating
      lymphocytes (TILs) are frequently found in BCC and SCC, and functionally promote
      epithelial carcinogenesis. TILs secreting IL-22, in particular, participate to
      BCC and SCC growth by inducing keratinocyte proliferation and migration, as well
      as the expression of inflammatory, anti-apoptotic and pro-angiogenic genes.In
      this study, we identified SOCS3 as a valid candidate to be manipulated for
      suppressing tumorigenic functions in BCC and SCC. We found that SOCS3 and SOCS1
      expression was reduced in vivo, in tumor lesions of BCC and SCC, as compared to
      other skin inflammatory conditions such as psoriasis, despite the high number of
      IL-22-secreting TILs. Moreover, IL-22 was not able to induce in vitro the
      transcriptional expression of SOCS3 in BCC-or SCC-derived keratinocytes,
      contrarily to healthy cells. Aimed at rescuing SOCS3 activity in these tumor
      contexts, a SOCS3-derived peptide, named KIR-ESS, was synthesized, and its
      ability in suppressing IL-22-induced responses was evaluated in healthy and
      transformed keratinocytes. We found that KIR-ESS peptide efficiently suppressed
      the IL-22 molecular signaling in keratinocytes, by acting on STAT3 and Erk1/2
      cascade, as well as on the expression of STAT3-dependent downstream genes.
      Interestingly, after treatment with peptide, both healthy and transformed
      keratinocytes could no longer aberrantly proliferate and migrate in response to
      IL-22. Finally, treatment of athymic nude mice bearing SCC xenografts with KIR
      ESS peptide concomitantly reduced tumor growth and activated STAT3 levels. As a
      whole, these data provides the rationale for the use in BCC and SCC skin tumors
      of SOCS3 mimetics, being able to inhibit the deleterious effects of IL-22 in
      these contexts.

PMID- 28445953
TI  - YEATS4 promotes the tumorigenesis of pancreatic cancer by activating beta
      catenin/TCF signaling.
AB  - Beta-catenin/TCF signaling has been reported to promote the growth and metastasis
      of pancreatic cancer cells. However, the regulation for the beta-catenin/TCF
      transcriptional complex remains largely unknown. Here, we have found that YEATS4
      is a positive regulator for Beta-catenin/TCF signaling. The expression of YEATS4
      was elevated in clinical pancreatic cancer samples and pancreatic cancer mouse
      model. Up-regulation of YEATS4 promoted the growth, migration and invasion of
      pancreatic cancer cells, while knocking down the expression of YEATS4 inhibited
      the growth, migration, invasion and metastasis of pancreatic cancer cells.
      Moreover, the mechanism study revealed that YEATS4 interacted with beta-catenin
      and activated beta-catenin/TCF signaling. Furthermore, knocking down the
      expression of YEATS4 impaired the malignant transformation of normal pancreatic
      cells (HPDE6C7) by the oncogenic Ras. Taken together, our study demonstrated the
      oncogenic roles of YEATS4 in the progression of pancreatic cancer by activating
      beta-catenin/TCF signaling and suggested that YEATS4 might be a promising
      therapeutic target for pancreatic cancer.

PMID- 28445954
TI  - A clinically feasible multiplex proteomic immunoassay as a novel functional
      diagnostic for pancreatic ductal adenocarcinoma.
AB  - To date, targeted therapy for pancreatic ductal adenocarcinoma (PDAC) remains
      largely unsuccessful in the clinic. Current genomics-based technologies are
      unable to reflect the quantitative, dynamic signaling changes in the tumor, and
      require larger tumor samples that are difficult to obtain in PDAC patients.
      Therefore, a highly sensitive functional tool that can reliably and
      comprehensively inform intra-tumoral signaling events is direly needed to guide
      treatment decision. We tested the utility of a highly sensitive proteomics-based
      functional diagnostic platform, Collaborative Enzyme Enhanced Reactive
      immunoassay (CEERTM), on fine-needle aspiration (FNA) samples obtained from 102
      patients with radiographically-evident pancreatic tumors. Two FNA passes were
      collected from each patient, hybridized to customized chips coated with an array
      of capture antibodies, and detected using two enzyme-conjugated antibodies which
      emit quantifiable signals. We demonstrate that this technique is highly sensitive
      in detecting total and phosphorylated forms of multiple signaling molecules in
      FNA specimens, with reasonable correlation of marker intensities between two
      different FNA passes. Notably, signals of several markers were significantly
      higher in PDAC compared to non-cancerous samples. In PDAC samples, we found high
      total c-Met signal to be associated with poor survival, and confirmed this
      finding using an independent PDAC tissue microarray.

PMID- 28445955
TI  - Metformin is associated with survival benefit in pancreatic cancer patients with
      diabetes: a systematic review and meta-analysis.
AB  - BACKGROUND: Pancreatic cancer is a highly lethal disease with a poor prognosis
      while metformin has been associated with a decreased risk of pancreatic cancer.
      Although the benefit of metformin was observed for pancreatic cancer prevention,
      it is not clear whether it can also affect the survival of pancreatic cancer
      patients with type 2 diabetes mellitus. A systematic review and meta-analysis was
      conducted to assess the effect of metformin on the survival of pancreatic cancer
      patients with type 2 diabetes mellitus. METHODS: Two independent authors searched
      PubMed and Web of science up to 08/07/2016. We assessed studies for eligibility,
      extracted data, and examined their quality, with the primary outcome as overall
      survival. We used published hazard ratio (HR) available or estimated based on
      other survival data. We pooled the data and used a random-effect model to combine
      direct comparisons from included articles. We also investigated treatment effects
      by different countries, quality and the time of metformin initiation. RESULTS: We
      found that there was a relative survival benefit associated with metformin
      treatment compared with non-metformin treatment in both overall survival (OS)
      ([HR] 0.84; 95% confidence interval [CI]: 0.73 - 0.96). These associations were
      also observed in subgroups of Asian countries and high quality articles.
      CONCLUSIONS: Our results support the notion that metformin maybe the best anti
      diabetic medicine of choice in patients with pancreatic cancer and concurrent
      type 2 diabetes mellitus. The perspectives of enhancing survival of pancreatic
      cancer patients with diabetes mellitus by the use of metformin deserve more
      attention in future research and clinical practice.

PMID- 28445956
TI  - RHBDD1 upregulates EGFR via the AP-1 pathway in colorectal cancer.
AB  - Our previous study showed that RHBDD1 can activate the EGFR signaling pathway to
      promote colorectal cancer growth. In the present study, EGFR was decreased when
      RHBDD1 was knocked down or inactivated. Further analysis found that c-Jun and
      EGFR protein expression was decreased in RHBDD1 knockdown and inactivated cells.
      c-Jun overexpression in RHBDD1-inactivated cells rescued EGFR expression in a
      dose-dependent manner. RHBDD1 overexpression in RHBDD1-inactivated cells restored
      EGFR expression, but this effect was counteracted by c-Jun knockdown.
      Furthermore, EGFR and c-Jun were attenuated in the RHBDD1 knockdown and
      inactivated groups in animal tumor models. Tissue microarray assays demonstrated
      a correlation between RHBDD1 and EGFR in colorectal cancer patients. Therefore,
      our findings indicate that RHBDD1 stimulates EGFR expression by promoting the AP
      1 pathway.

PMID- 28445957
TI  - Peripheral kynurenine/tryptophan ratio is not a reliable marker of systemic
      indoleamine 2,3-dioxygenase: A lesson drawn from patients on hemodialysis.
AB  - Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating
      immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma
      kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of
      systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp
      ratio to estimate cell-mediated immune responses to tuberculin skin testing and
      risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel
      IDO marker, the IDO median fluorescence index (MFI) of peripheral blood
      mononuclear cells, which was determined by flow cytometry. In 228 patients from
      two hemodialysis centers, the two IDO markers were higher in patients than in
      healthy controls but were not correlated with each other. In vitro experiments
      demonstrated that peripheral blood mononuclear cells could not metabolize
      tryptophan into kynurenine, indicating that the increased Kyn/Trp ratio was IDO
      independent. Skin induration diameters of tuberculin skin testing were correlated
      with the IDO MFI (negatively), but not the Kyn/Trp ratio. Further, in a 24-month
      prospective cohort, the Kyn/Trp ratio was not correlated with clinical infection.
      Alternatively, patients with a higher IDO MFI had a lower accumulative infection
      free survival rate. Using a Cox proportional hazard model, it was also revealed
      that a higher IDO MFI was significantly associated with new bacterial infection.
      Taken together, these results indicate that the Kyn/Trp ratio is not a reliable
      circulating IDO marker in hemodialysis patients. However, the IDO MFI reflects an
      immunocompromised state and thus might be a potential clinical marker of
      bacterial infection.

PMID- 28445958
TI  - Repressing CD147 is a novel therapeutic strategy for malignant melanoma.
AB  - CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super
      family. Accumulating evidence has revealed the role of CD147 in the development
      and progression of various cancers, including malignant melanoma (MM). MM is a
      malignancy of pigment-producing cells that causes the greatest number of skin
      cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an
      important role in cell viability, apoptosis, proliferation, invasion, and
      metastasis, probably by mediating vascular endothelial growth factor (VEGF)
      production, glycolysis, and multi-drug resistance (MDR). As a matrix
      metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts
      to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting
      CD147 has been shown to suppress MM in vitro and in vivo, highlighting the
      therapeutic potential of CD147 silencing in MM treatment. In this review article,
      we discuss CD147 and its biological roles, regulatory mechanisms, and potential
      application as a molecular target for MM.

PMID- 28445961
TI  - Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues
      characteristic parkinsonian behaviors in a rat model of Parkinson's disease.
AB  - Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological
      hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms.
      Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced
      apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these
      findings needed to be confirmed via animal experiments. Here, using a rotenone
      induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the
      SN, since Ang II level and AT1R expression were markedly increased. Furthermore,
      we provided in vivo evidence that Ang II directly elicited apoptosis of
      dopaminergic neurons via activation of AT1R in the SN of rats. More importantly,
      we showed for the first time that oral administration of azilsartan, a newly
      developed AT1R blocker approved by the U.S. Food and Drug Administration for
      hypertension treatment, rescued the apoptosis of dopaminergic neurons and
      relieved the characteristic parkinsonian symptoms in PD rats. These results
      support the application of AT1R blockers in PD therapy, and strengthen the notion
      that many therapeutic agents may possess pleiotropic action in addition to their
      main applications.

PMID- 28445960
TI  - Effect of folate deficiency on promoter methylation and gene expression of Esr1,
      Cav1, and Elavl1, and its influence on spermatogenesis.
AB  - This study aims to investigate the effect of folate deficiency on the male
      reproductive function and the underlying mechanism. A total of 269 screened
      participants from 421 recruitments were enrolled in this study. An animal model
      of folate deficiency was constructed. Folate concentration was measured in the
      ejaculate, and its association with semen parameters was then determined. The
      expression and promoter methylation status of ESR1, CAV1, and ELAVL1 were also
      evaluated. Results showed that seminal plasma folate level was significantly
      lower among subjects with azoospermia than those with normozoospermia. Low folate
      level was significantly correlated with low sperm concentration in men with
      normozoospermia. Folate deficiency significantly reduced the expression of ESR1,
      CAV1, and ELAVL1, which are critical to spermatogenesis. However, low folate
      levels did not increase the methylation levels of the promoter regions of ESR1,
      CAV1, and ELAVL1 in human sperm DNA. Thus, folate deficiency impairs
      spermatogenesis may partly due to inhibiting the expression of these genes. Thus
      future research should determine the significance of sufficient folate status in
      male fertilization and subsequent pregnancy outcomes.

PMID- 28445959
TI  - Brain metastases from hepatocellular carcinoma: recent advances and future
      avenues.
AB  - The incidence of brain metastases from hepatocellular carcinoma (BMHCC) is
      becoming more frequent than that of the past as a result of prolonged survival of
      patients with HCC. Compared with brain metastases from other types of cancer,
      BMHCC tends to exhibit a high incidence of intracerebral hemorrhage (ICH) and
      poor liver function. Unfortunately, the prognosis is extremely poor for patients
      with BMHCC owing to the limited treatment selection. Currently, optimal treatment
      requires multidisciplinary approaches including surgery, whole-brain radiation
      therapy and stereotactic radiosurgery. Besides these traditional approaches,
      novel treatments such as target therapy and immunotherapy provide an opportunity
      to improve the survival of these patients. This review provides an overview of
      the incidence, characteristics, prognosis, and current and potential future
      management strategies for BMHCC.

PMID- 28445962
TI  - PSMA-homing dsRNA chimeric protein vector kills prostate cancer cells and
      activates anti-tumor bystander responses.
AB  - The treatment of metastatic androgen-resistant prostate cancer remains a
      challenge. We describe a protein vector that selectively delivers synthetic
      dsRNA, polyinosinic/polycytidylic acid (polyIC), to prostate tumors by targeting
      prostate specific membrane antigen (PSMA), which is overexpressed on the surface
      of prostate cancer cells.The chimeric protein is built from the double stranded
      RNA (dsRNA) binding domain of PKR tethered to a single chain anti-PSMA antibody.
      When complexed with polyIC, the chimera demonstrates selective and efficient
      killing of prostate cancer cells. The treatment causes the targeted cancer cells
      to undergo apoptosis and to secrete toxic cytokines. In a "bystander effect",
      these cytokines kill neighboring cancer cells that do not necessarily overexpress
      PSMA, and activate immune cells that enhance the killing effect. The strong
      effects of the targeted polyIC are demonstrated on both 2D cell cultures and 3D
      tumor spheroids.

PMID- 28445963
TI  - Genetic polymorphisms of Bcl-2 promoter in cancer susceptibility and prognosis: a
      meta-analysis.
AB  - Bcl-2 is critical for tumorigenesis. However, previous studies on the association
      of Bcl-2 promoter polymorphisms with predisposition to different cancer types are
      somewhat contradictory. Therefore, we performed this meta-analysis regarding the
      relationship between Bcl-2 promoter single nucleotide polymorphisms (SNPs) and
      cancer susceptibility and prognosis. Up to August 2016, 32 original publications
      were identified covering two Bcl-2 promoter SNPs (rs2279115 and rs1801018). Our
      results showed statistically significant association between rs2279115 and cancer
      susceptibility and prognosis in all four genetic models but not in rs1801018.
      Subgroups analysis indicated that rs2279115 was associated with a significantly
      higher risk of cancer susceptibility in Asia but not in Caucasian. Furthermore,
      rs2279115 was associated with a significantly higher risk in digestive system
      cancer and endocrine system cancer but not in breast cancer, respiratory cancer
      and hematopoietic cancer. Simultaneously, rs2279115 was correlated with a
      significantly higher risk of cancer prognosis in Asia but not in Caucasian.
      Considering these promising results, rs2279115 may be a tumor marker for
      cancertherapy in Asia. Sensitivity analysis show four gene model were stable, and
      no publication bias was observed in all four gene model. Large sample size,
      different ethnic population and different cancer type are warranted to validate
      this association.

PMID- 28445964
TI  - ABO blood group and ovarian reserve: a meta-analysis and systematic review.
AB  - Ovarian reserve reflects a woman's fertility potential. The ABO blood group
      system is a very stable genetic marker. Although many recent studies have
      explored the relationship between ABO blood group and ovarian reserve, a
      consensus has not yet been reached. This paper is the first meta-analysis and
      systematic review of the relationship between ABO blood type and ovarian reserve.
      We analyzed seven cross-sectional studies evaluating follicle stimulating hormone
      (FSH) or anti-Mullerian hormone (AMH) levels in 55,113 participants to determine
      ovarian reserve. This study found no relationship between ABO blood type and
      ovarian reserve when FSH was used as an indicator of ovarian reserve (A vs non
      A:OR=1.03, 95% CI:0.96-1.11; B vs non-B: OR=0.98, 95% CI:0.75-1.29; AB vs non
      AB:OR=0.96, 95% CI:0.71-1.30; O vs non-O:OR=1.03, 95%CI:0.74-1.43).There was also
      no relationship between ABO blood type and ovarian reserve when AMH was used as
      an indicator (A vs non-A:OR=0.89, 95% CI:0.76-1.03; B vs non-B:OR=1.02, 95%
      CI:0.80-1.30; AB vs non-AB:OR=1.14, 95% CI:0.80-1.64, O vs non-O:OR=1.07, 95%
      CI:0.86-1.34). Overall, the current study found no relationship between ABO blood
      group and ovarian reserve. However, additional rigorous, high-quality and multi
      indicator studies with large sample sizes are required for further verification.

PMID- 28445965
TI  - Molecular docking, 3D-QSAR and structural optimization on imidazo-pyridine
      derivatives dually targeting AT1 and PPARg.
AB  - Telmisartan, a bifunctional agent of blood pressure lowering and glycemia
      reduction, was previously reported to antagonize angiotensin II type 1 (AT1)
      receptor and partially activate peroxisome proliferator-activated receptor gamma
      (PPARgamma) simultaneously. Through the modification to telmisartan, researchers
      designed and obtained imidazo-?pyridine derivatives with the IC50s of 0.49~94.1
      nM against AT1 and EC50s of 20~3640 nM towards PPARgamma partial activation. For
      minutely inquiring the interaction modes with the relevant receptor and analyzing
      the structure-activity relationships, molecular docking and 3D-QSAR (Quantitative
      structure-activity relationships) analysis of these imidazo-?pyridines on dual
      targets were conducted in this work. Docking approaches of these derivatives with
      both receptors provided explicit interaction behaviors and excellent matching
      degree with the binding pockets. The best CoMFA (Comparative Molecular Field
      Analysis) models exhibited predictive results of q2=0.553, r2=0.954, SEE=0.127,
      r2pred=0.779 for AT1 and q2=0.503, r2=1.00, SEE=0.019, r2pred=0.604 for
      PPARgamma, respectively. The contour maps from the optimal model showed detailed
      information of structural features (steric and electrostatic fields) towards the
      biological activity. Combining the bioisosterism with the valuable information
      from above studies, we designed six molecules with better predicted activities
      towards AT1 and PPARgamma partial activation. Overall, these results could be
      useful for designing potential dual AT1 antagonists and partial PPARgamma
      agonists.

PMID- 28445966
TI  - Interferon alpha antagonizes the anti-hepatoma activity of the oncolytic virus M1
      by stimulating anti-viral immunity.
AB  - Alpha virus M1 is an oncolytic virus that targets zinc-finger antiviral protein
      (ZAP)-defective cancer cells, and may be useful for treatment of hepatocellular
      carcinoma (HCC). Most of HCC patients have hepatitis and need long-term antiviral
      medication. Thus, it is necessary to clarify whether anti-virus medicines
      influence oncolytic effect of M1. We examined the effect of drugs used to treat
      hepatitis B/C on M1-mediated oncolysis in vitro and in vivo. Interferon (IFN)
      alpha induces expression of antiviral IFN-stimulated genes (ISGs) in HCC cells
      with moderate sensitivity to M1 virus. This leads to reduced replication of M1,
      and blocking of M1-mediated apoptosis. The antagonistic effect of IFN-alpha is
      positively related with the expressive level of ISGs. We also examined a
      population of 147 HCC patients. A total of 107 patients (73%) had low ZAP
      expression in liver tissues relative to adjacent tissues. Among these 107
      patients, 77% were positive for hepatitis B and 2% were positive for hepatitis C.
      A combination of M1 virus and IFN should be avoided in those patients with HBV or
      HCV infection, of who ZAP expression is low but ISGs expression is moderate. In
      conclusion, this study provides a basis for anti-viral regimens for HCC patients
      with hepatitis B or C who are given oncolytic virus M1.

PMID- 28445967
TI  - Lactobacillus casei Zhang and vitamin K2 prevent intestinal tumorigenesis in mice
      via adiponectin-elevated different signaling pathways.
AB  - The incidence of colon cancer has increased considerably and the intestinal
      microbiota participate in the development of colon cancer. We showed that the L.
      casei Zhang or vitamin K2 (Menaquinone-7) intervention significantly alleviated
      intestinal tumor burden in mice. This was associated with increased serum
      adiponectin levels in both treatments. But osteocalcin level was only increased
      by L. casei Zhang. Furthermore, the anti-carcinogenic actions of L. casei Zhang
      were mediated by hepatic Chloride channel-3(CLCN3)/Nuclear Factor Kappa B(NF
      kappaB) and intestinal Claudin15/Chloride intracellular channel
      4(CLIC4)/Transforming Growth Factor Beta(TGF-beta) signaling, while the vitamin
      K2 effect involved a hepatic Vitamin D Receptor(VDR)-phosphorylated AMPK
      signaling pathway. Fecal DNA sequencing by the Pacbio RSII method revealed there
      was significantly lower Helicobacter apodemus, Helicobacter mesocricetorum,
      Allobaculum stercoricanis and Adlercreutzia equolifaciens following both
      interventions compared to the model group. Moreover, different caecum acetic acid
      and butyric acid levels and enrichment of other specific microbes also determined
      the activity of the different regulatory pathways. Together these data show that
      L. casei Zhang and Vitamin K2 can suppress gut risk microbes and promote
      beneficial microbial metabolites to reduce colonic tumor development in mice.

PMID- 28445969
TI  - Glypican-1 targeted antibody-based therapy induces preclinical antitumor activity
      against esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) has a poor prognosis despite the
      development of multimodal therapy. Expression of glypican-1 (GPC1) has been
      reported to be elevated in a subset of patients with ESCC and associated with
      chemoresistance. This study aimed to determine the association of GPC1 with ESCC
      growth and potential usefulness of the GPC1 targeted therapy by monoclonal
      antibody (mAb) in ESCC. Expression of GPC1 was higher in ESCC tumor tissues than
      in adjacent non-tumoral tissues and normal tissues. Knockdown of GPC1 decreased
      growth of ESCC cells and induced apoptosis via inhibition of EGFR, AKT and p44/42
      MAPK signaling pathways in vitro. Anti-GPC1 mAb strongly inhibited tumor growth
      via antibody-dependent cellular cytotoxicity dependent and independent manner in
      GPC1-positive ESCC xenograft models. Anti-GPC1 mAb also inhibited tumor growth of
      GPC1 positive ESCC patients derived tumor xenograft models. Furthermore, anti
      GPC1 mAb showed a significant tumor growth inhibition with decreased angiogenesis
      compared with IgG treated controls in ESCC xenografted mice. Treatment with anti
      GPC1 mAb was not toxic in mice. Anti-GPC1 mAb may have a potent anti-tumor effect
      and represent a novel treatment option for patients with GPC1-positive ESCC.

PMID- 28445968
TI  - USP22 knockdown enhanced chemosensitivity of hepatocellular carcinoma cells to 5
      Fu by up-regulation of Smad4 and suppression of Akt.
AB  - USP22, a member of the deubiquitinases (DUBs) family, is known to be a key
      subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional
      cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins,
      thus regulating the transcription and expression of downstream genes. USP22 plays
      important roles in many cancers; however, its effect and the mechanism underlying
      HCC chemoresistance remain unclear. In the present study, we found that USP22 was
      highly expressed in chemoresistant HCC tissues and cells and was correlated with
      the prognosis of HCC patients who received chemotherapy. Silencing USP22 in
      chemoresistant HCC Bel/Fu cells dramatically inhibited proliferation, migration,
      invasion and epithelial-mesenchymal transition in vitro; suppressed tumorigenic
      and metastatic capacities in vivo; and inhibited drug resistance-related proteins
      (MDR1, LRP, MRP1). Mechanistically, we found that USP22 knockdown exerts its
      function through down-regulating PI3K and activating Smad4, which inhibited
      phosphorylation of Akt. Silencing Smad4 blocked USP22 knockdown-induced Akt
      inhibition in Bel/Fu cells. Our results, for the first time, provide evidence
      that USP22 plays a critical role in the development of chemoresistant HCC cells
      and that high USP22 expression serves as a molecular marker for the prognosis of
      HCC patients who undergo chemotherapy.

PMID- 28445971
TI  - STAT3 regulates glycolysis via targeting hexokinase 2 in hepatocellular carcinoma
      cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2)
      are involved in hepatocellular carcinoma (HCC). Deregulation of cellular
      energetics involving an increase in glycolysis is a characteristic of HCC. This
      study examined whether STAT3 regulates HCC glycolysis through the HK2 pathway in
      HCC cells. Human HCC cell lines HepG2 and Hep3B cells were transfected with
      pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with
      rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects
      on STAT3 and HK2 expression and cell glycolysis were determined. STAT3 and HK2
      expressions were evaluated by real-time polymerase chain reaction and Western
      blotting. The level of glycolysis metabolism was assessed by the determination of
      glucose consumption and lactate production.The results showed that transfection
      of HepG2 and Hep3B cells with pcDNA3.1(+)-EGFP-STAT3 significantly increased
      STAT3 mRNA and protein expression, glucose consumption and lactate production,
      and HK2 mRNA and protein expression. However, transfection of HepG2 and Hep3B
      cells with STAT3 siRNA significantly decreased glucose consumption and lactate
      production and HK2 mRNA and protein expression. Transfection of HepG2 and Hep3B
      cells with HK2 siRNA significantly decreased glucose consumption and lactate
      production. Treatment of HepG2 and Hep3B cells with rapamycin significantly
      reduced HK2 mRNA and protein expression and glucose consumption and lactate
      production. These results suggest that mTOR-STAT3-HK2 pathway is involved in the
      glycolysis of HCC cells and STAT3 may regulate HCC glycolysis through HK2
      pathway, providing potential multiple therapeutic targets through intervention of
      glycolysis for the treatment of HCC.

PMID- 28445970
TI  - Acid ceramidase is a novel drug target for pediatric brain tumors.
AB  - Pediatric brain tumors are the most common solid tumors in children and are also
      a leading culprit of cancer-related fatalities in children. Pediatric brain
      tumors remain hard to treat. In this study, we demonstrated that medulloblastoma,
      pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant
      levels of acid ceramidase, where levels are highest in the radioresistant tumors,
      suggesting that acid ceramidase may confer radioresistance. More importantly, we
      also showed that acid ceramidase inhibitors are highly effective at targeting
      these pediatric brain tumors with low IC50 values (4.6-50 MUM). This data
      suggests acid ceramidase as a novel drug target for adjuvant pediatric brain
      tumor therapies. Of these acid ceramidase inhibitors, carmofur has seen clinical
      use in Japan since 1981 for colorectal cancers and is a promising drug to undergo
      further animal studies and subsequently a clinical trial as a treatment for
      pediatric patients with brain tumors.

PMID- 28445972
TI  - The prognostic value of D-dimer levels in endometrial cancer patients treated
      with intensity-modulated radiation therapy.
AB  - Explain the important role of plasma D-dimer in cancers. Plasma D-dimer is
      increased in various tumors. However, the predictive value of plasma D-dimer is
      unclear. This study is aimed to evaluate the prognostic value of the D-dimer
      level in patients managed with intensity-modulated radiation for endometrial
      cancer. The D-dimer levels of forty patients with endometrial cancer were
      assessed before (D1) and after (D2) intensity-modulated radiation therapy (IMRT),
      respectively. The D-dimer level changes (DeltaD) were defined as D2 minus D1. Cox
      regression and log-rank tests were used to evaluate the D-dimer levels in
      relation to progression free survival (PFS) and overall survival (OS). The OS and
      PFS of patients with a low D1 were significantly longer than those with a high D1
      (P< 0.001, P< 0.001). We saw the similar correlation between D2, PFS and OS (P<
      0.001, P< 0.001). Multivariate survival analyses showed that D-dimer was
      independently associated with OS and PFS in patients with endometrial cancer. The
      DeltaD level was not related to the OS and PFS in endometrial cancer patients.
      The levels of D-dimer may be considered as an important predictor of PFS and OS
      in endometrial cancer patients treated with IMRT.

PMID- 28445973
TI  - Plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3
      delivery vector.
AB  - We have previously demonstrated that malaria parasite infection has an anti-tumor
      effect in a mouse model. This research aimed to investigate the possibility of
      using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma
      (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.y)
      expressing murine glypican-3 (GPC3) protein (P.y-GPC3), and examined its
      therapeutic potency in a murine Hepa1-6-induced hepatoma model that highly
      expressed GPC3 protein. The prerequisites for invoking a CD8+ T cell response
      were assessed after P.y-based immunization, which included obviously increased
      concentrations of T helper cell type 1 (Th1)-associated cytokines, such as IL-2,
      IFN-gamma and TNF-alpha, in serum and preferential expansion of the CD8alpha+
      dendritic cell (DC) subset with higher expression of CD80 and CD86 molecules.
      Compared with uninfected and wild-type P.y-infected mice, a significant GPC3
      specific cytotoxic T lymphocyte (CTL) response was detected in P.y-GPC3
      vaccinated mice. Furthermore, P.y-GPC3-based vaccination dramatically inhibited
      Hepa1-6-induced tumor growth in the implanted HCC and prolonged the survival of
      tumor-bearing mice. We concluded that a Plasmodium-based vector is highly
      efficient in inducing tumor antigen-specific T cell-mediated immunity and
      protection against tumor cells. More broadly, this strategy supported our
      hypothesis that Plasmodium parasites, as novel therapeutic antigen vectors, may
      be applicable to tumor immunotherapy for patients with HCC.

PMID- 28445974
TI  - Lowered expression of microRNA-125a-5p in human hepatocellular carcinoma and up
      regulation of its oncogenic targets sirtuin-7, matrix metalloproteinase-11, and c
      Raf.
AB  - Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it
      downregulates the expression of membrane receptors or intracellular transductors
      of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA
      generally increases with cell differentiation whereas it is downregulated in
      several types of tumors, such as breast, lung, ovarian, gastric, colon, and
      cervical cancers, neuroblastoma, medulloblastoma, glioblastoma, and
      retinoblastoma. In this study, we focused on hepatocellular carcinoma and used
      real-time quantitative PCR to measure miR-125a expression in 55 tumor biopsies
      and in matched adjacent non-tumor liver tissues. This analysis showed a
      downregulation of miR-125a in 80 % of patients, with a mean decrease of 4.7-fold.
      Comparison of miRNA downregulation with clinicopathological parameters of
      patients didn't yield significant correlations except for serum bilirubin. We
      then evaluated the expression of known targets of miR-125a and found that sirtuin
      7, matrix metalloproteinase-11, and c-Raf were up-regulated in tumor tissue by
      2.2-, 3-, and 1.7-fold, respectively. Overall, these data support a tumor
      suppressor role for miR-125a and encourage further studies aimed at the
      comprehension of the molecular mechanisms governing its expression, eventually
      leading to treatments to restore its expression in tumor cells.

PMID- 28445975
TI  - Functional FGFR4 Gly388Arg polymorphism contributes to cancer susceptibility:
      Evidence from meta-analysis.
AB  - Fibroblast growth factor receptor 4 (FGFR4) is a member of receptor tyrosine
      kinase family. A functional Gly388Arg (rs351855 G>A) polymorphism in FGFR4 gene
      causes a glycine-to-arginine change at codon 388 within the transmembrane domain
      of the receptor. Although the FGFR4 rs351855 G>A polymorphism has been implicated
      in cancer development, its association with cancer risk remains controversial.
      Here, we have systematically analyzed the association between the rs351855 G>A
      polymorphism and cancer risk by performing a meta-analysis of 27 studies
      consisting of 8,682 cases and 9,731 controls. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated to measure the strength of the
      association. The rs351855 G>A polymorphism was associated with an increased
      cancer risk under the recessive model (OR=1.19, 95% CI=1.01-1.41). Stratified
      analysis by cancer type indicated the rs351855 G>A polymorphism was associated
      with an increased risk of breast and prostate cancer, but a decreased risk of
      lung cancer. This meta-analysis demonstrates the FGFR rs351855 G>A polymorphism
      is associated with increased cancer risk and suggests it could potentially serve
      as a chemotherapeutic target or biomarker to screen high-risk individuals.

PMID- 28445976
TI  - Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma.
AB  - Reactive oxygen species (ROS) play important roles in follicular development and
      survival. Granulosa cell death is associated with increased ROS, but the
      mechanism of granulosa cell death induced by ROS is not clear. In order to define
      the molecular link between ROS and granulosa cell death, COV434, human granulosa
      tumor cells, were treated with H2O2. Compared to control cells, H2O2 induced
      granulosa cell death in a dose- and time-dependent manner. H2O2 induced an
      increase in Bax, Bak and Puma, and a decrease in anti-apoptotic molecules such as
      Bcl-2, Bcl-xL and Mcl-1. Both knockdown of Puma and overexpression of Bcl-xL
      could inhibit H2O2-induced granulosa cell death. These results suggest that
      suppression of Puma and overexpression of anti-apoptotic Bcl-2 family members
      could improve granulosa cell survival. To explore the mechanisms responsible for
      these findings, ROS in granulosa cells treatment with H2O2 were measured. The
      results showed that ROS was increased in a H2O2 dose- and time-dependent manner
      at the earlier time point. In addition, H2O2 induced an increase in Nrf2 and
      phosphorylation of JNK and p53. SP600125, an inhibitor of JNK, inhibits H2O2
      induced phosphorylation of JNK and p53, and granulosa cell death. Antioxidant N
      acetylcysteine (NAC) dose-dependently prevents H2O2-induced granulosa cell death.
      Furthermore, NAC also prevents phosphorylation of JNK and p53 induced by H2O2.
      Taken together, these data suggest that H2O2 regulates cell death in granulosa
      cells via the ROS-JNK-p53 pathway. These findings provide an improved
      understanding of the mechanisms underlying granulosa cell apoptosis, which could
      potentially be useful for future clinical applications.

PMID- 28445977
TI  - Serglycin as a potential biomarker for glioma: association of serglycin
      expression, extent of mast cell recruitment and glioblastoma progression.
AB  - Serglycin is an intracellular proteoglycan with a unique ability to adopt highly
      divergent structures by glycosylation with variable types of glycosaminoglycans
      (GAGs) when expressed by different cell types. Serglycin is overexpressed in
      aggressive cancers suggesting its protumorigenic role. In this study, we explored
      the expression of serglycin in human glioma and its correlation with survival and
      immune cell infiltration. We demonstrate that serglycin is expressed in glioma
      and that increased expression predicts poor survival of patients. Analysis of
      serglycin expression in a large cohort of low- and high-grade human glioma
      samples reveals that its expression is grade dependent and is positively
      correlated with mast cell (MC) infiltration. Moreover, serglycin expression in
      patient-derived glioma cells is significantly increased upon MC co-culture. This
      is also accompanied by increased expression of CXCL12, CXCL10, as well as markers
      of cancer progression, including CD44, ZEB1 and vimentin.In conclusion, these
      findings indicate the importance of infiltrating MCs in glioma by modulating
      signaling cascades involving serglycin, CD44 and ZEB1. The present investigation
      reveals serglycin as a potential prognostic marker for glioma and demonstrates an
      association with the extent of MC recruitment and glioma progression, uncovering
      potential future therapeutic opportunities for patients.

PMID- 28445978
TI  - Epidemiological features of lung giant cell carcinoma and therapy for patients
      with EGFR mutations based on case reports and the surveillance, epidemiology, and
      end results (SEER) database.
AB  - Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the
      standard first line treatment for advanced non-small cell lung cancer (NSCLC)
      with sensitive EGFR mutations. Among NSCLC, giant cell carcinoma of the lung
      (GCCL) is a rare pathological subtype with poor prognosis, with no confirmed
      evidence about its epidemiological features or therapeutic efficiency of EGFR
      TKIs. We present two advanced GCCLs with sensitive EGFR mutations, also collected
      the cases of GCCL from our hospital and the Surveillance, Epidemiology, and End
      Results (SEER) program. Kaplan-Meier methods and Cox proportional hazards
      modeling were used to perform the survival analyses. Both two cases of advanced
      GCCL with sensitive EGFR mutations benefited from EGFR-TKIs. Twelve GCCLs were
      recorded in our hospital from May 2006 to July 2015. GCCL is associated with
      males (83.3%) and smoking status (63.6%). The EGFR mutation rate was 40.0%. In
      SEER database, the total number of GCCLs was 184, 0.11% for all NSCLCs. In Kaplan
      Meier analysis, the 5-year overall survival of GCCL patients was significantly
      lower than that of non-GCC NSCLC (16% and 19%; P<0.001), and it was confirmed in
      multivariate analysis. Further survival analyses indicated that male were more
      susceptible to GCCL and GCCL was prone to metastasize. Only age and M stage were
      independent prognostic factors for GCCL in the multivariate analysis. In
      conclusion, GCCL was an unfavorable prognostic factor and associated with males
      and metastasis. GCCL patients with sensitive EGFR mutations may also benefit from
      EGFR-TKI, we therefore recommend the evaluation of EGFR in the treatment of
      advanced GCCL.

PMID- 28445979
TI  - The impacts of single nucleotide polymorphisms in genes of cell cycle and NF-kB
      pathways on the efficacy and acute toxicities of radiotherapy in patients with
      nasopharyngeal carcinoma.
AB  - Radiotherapy is one of the primary choices for the treatment of nasopharyngeal
      carcinoma (NPC) and may result in severe radiotoxicities on normal tissues.
      Single nucleotide polymorphisms (SNPs) in genes of cell cycle and NF-kappaB
      pathways have been linked with the prognoses of various cancers. The aim of this
      study was to explore whether SNPs of genes involved in cell cycle and NF-kappaB
      pathways are associated with responses to radiotherapy in NPC patients. We
      selected 3 SNPs in cell cycle pathway and 5 SNPs in NF-kappaB pathway and
      genotyped them in 154 NPC patients treated with radiotherapy. Multivariate
      logistic regression was used to determine the association of these 8 SNPs with
      the responses to radiotherapy. We observed that cyclin-dependent kinase inhibitor
      gene CDKN2A rs3088440 was significantly related with a poorer treatment efficacy
      on the primary tumor and cervical lymph node after radiotherapy, and also with a
      decreased risk of grade 3-4 acute radiation-induced myelosuppression. In some
      subgroups, cyclin D1 gene CCND1 rs9344 and inhibitor of kappaB kinase gene IKBKB
      rs12676482 were related with the grade 3-4 acute radiation-induced
      myelosuppression, and CCND1 rs9344 was also associated with grade 3-4 acute
      radiation-induced oral mucositis. The current results reveal that SNPs in genes
      of cell cycle pathwayand NF-kappaB pathway have the potential to predict the
      clinical responses to radiotherapy for NPC patients.

PMID- 28445980
TI  - The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF
      kappaB by merkel polyomavirus small tumour antigen.
AB  - Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high
      metastatic potential. The majority of MCC cases are caused by the Merkel cell
      polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens.
      Whilst mechanisms attributing tumour antigen expression to transformation are
      being uncovered, little is known of the mechanisms by which MCPyV persists in the
      host. We previously identified the MCPyV small T antigen (tAg) as a novel
      inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the
      host anti-viral response. Here we demonstrate that regulation of NF-kB activation
      involves a previously undocumented interaction between tAg and regulatory sub
      unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and
      PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing
      deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact
      with components of this complex, or siRNA depletion of PP4R1, prevents tAg
      mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison
      of tAg binding partners from other human polyomavirus demonstrates that
      interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data
      identify PP4R1 as a novel target for virus subversion of the host anti-viral
      response.

PMID- 28445981
TI  - MiR-148a increases glioma cell migration and invasion by downregulating GADD45A
      in human gliomas with IDH1 R132H mutations.
AB  - High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in
      the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In
      this study, we investigated which genes are differentially regulated in IDH1 wild
      type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth
      arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microRNA
      148a (miR-148a) was upregulated in in IDH1R132H human glioblastomas tissues. The
      relationship between GADD45A and miR-148a is unknown. In vitro experiments showed
      that GADD45A negatively regulates IDH1R132H glioma cell proliferation, migration,
      and invasion, and neurosphere formation in IDH1R132H glioblastoma stem cells
      (GSC). In addition, a human orthotopic xenograft mouse model showed that GADD45A
      reduced tumorigenesis in vivo. Our findings demonstrated that miR-148a promotes
      glioma cell invasion and tumorigenesis by downregulating GADD45A. Our findings
      provide novel insights into how GADD45A is downregulated by miR-148a in IDH1R132H
      glioma and may help to identify therapeutic targets for the effective treatment
      of high-grade glioma.

PMID- 28445982
TI  - Serum uric acid level as a cardio-cerebrovascular event risk factor in middle
      aged and non-obese Chinese men.
AB  - AIM: The role of uric acid as a risk factor for cardio-cerebrovascular diseases
      is controversial. In this study, we aimed to investigate the relationship between
      serum uric acid level and the risk of cardio-cerebrovascular events in middle
      aged and non-obese Chinese men. METHODS: We included 3152 participants from the
      health examination center of Tongji Hospital from June 2007 to June 2010.
      Clinical examination and medical records were collected at the annual health
      examination. The hazard ratios (HRs) of uric acid for cardio-cerebrovascular
      events were calculated by Cox proportional hazards models. Generalized additive
      model and threshold effect analysis were used to explore the non-linear
      relationship between serum uric acid level and the incidence of cardio
      cerebrovascular event. RESULT: The mean follow-up time was 52 months. When the
      participants were classified into four groups by the serum acid quarter (Q1-Q4),
      the HRs (95% CI) of Q2-Q4 for cardio-cerebrovascular events were 1.26 (0.83,
      1.92), 1.97 (1.33, 2.91) and 2.05 (1.40, 3.01), respectively, compared with the
      reference (Q1). The actual incidence and conditional incidence of cardio
      cerebrovascular events in the high serum acid group were higher than those in the
      low serum acid group, which were stratified by the turning point (sUA = 372
      MUmol/L). We also showed a strong prognostic accuracy of the multiple variable
      based score in 3 years and 5 years, with area under the receiver operating
      characteristic (ROC) curve of 0.790 (0.756-0.823) and 0.777 (0.749-0.804),
      respectively. CONCLUSION: Serum uric acid level is a strong risk factor for
      cardio-cerebrovascular events.

PMID- 28445983
TI  - Transport stress induces weight loss and heart injury in chicks: disruption of
      ionic homeostasis via modulating ion transporting ATPases.
AB  - Transportation is inevitable in the poultry industry, and it can induce stress to
      chicks in varying degrees, such as mild discomfort, sometimes even death.
      However, the research about the effects of transport stress on the weight loss
      and heart injury of chicks is lacking. To elucidate the underlying mechanism of
      transport stress-induced effects, chicks were transported for 2h, 4h and 8h. The
      creatinine kinase (CK) activities, the ionic contents, the ATPases activities and
      the transcription of the ATPase associated subunits in chick heart were detected.
      The results showed that transport stress increased the weight loss and the CK
      activity, disturbed the ionic (K+, Ca2+, Mg2+) homeostasis and inhibited the
      ATPase (Na+-K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and Ca2+-Mg2+-ATPase) activities,
      increased the ATP content and downregulated the gene expression levels of the
      ATPase associated subunits in heart. In conclusion, transport stress disturbed
      the ionic homeostasis via modulating ion transporting ATPases and the
      transcriptions of the associated subunits, and ultimately induced weight loss and
      heart injury in chicks.

PMID- 28445984
TI  - Paraoxonase 1 gene polymorphisms are associated with an increased risk of breast
      cancer in a population of Chinese women.
AB  - In this study, we explored associations between paraoxonase 1 (PON1) L55M and
      Q192R gene polymorphisms and the risk of breast cancer in 365 female breast
      cancer patients and 378 healthy controls from the Guangxi region of southern
      China. The LM heterozygous and MM homozygous genotypes, as well as M carrier
      status and M alleles, were associated with an increased risk of breast cancer. In
      addition, the M allele was associated with postmenopausal status and increased
      nodal involvement. In contrast, none of the Q192R genotypes or alleles were
      associated with a change in breast cancer risk, or with any of the
      clinicopathological parameters. These results indicate that PON1 L55M genetic
      polymorphisms may be associated with the risk of breast cancer and could
      potentially serve as useful genetic markers for tumor prognosis in some
      populations of Chinese women.

PMID- 28445985
TI  - Interleukin-22 promotes aerobic glycolysis associated with tumor progression via
      targeting hexokinase-2 in human colon cancer cells.
AB  - Interleukin-22 has been explored extensively in human cancer, but its functions
      and underlying mechanisms are incompletely understood. Here, we show that
      aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer
      cells. Elevated interleukin-22 mRNA expression was observed and positively
      correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22
      enhanced glucose consumption and lactate production via targeting hexokinase-2 in
      colon cancer cells. Moreover, the transcriptional factor c-Myc and signal
      transducer and activator of transcription 3 were involved in interleukin-22
      induced up-regulation of hexokinase-2. We further demonstrated that hexokinase-2
      partly accounted for interleukin-22-mediated cellular proliferation in DLD-1
      cells. In vivo, our data demonstrated that interleukin-22 significantly promoted
      tumor growth along with elevated expression of c-Myc and hexokinase-2 in mice. In
      summary, our findings provide a new perspective on the pro-inflammatory cytokine
      interleukin-22 in promoting aerobic glycolysis associated with tumor progression
      in human colon cancer cells.

PMID- 28445986
TI  - High BMI1 mRNA expression in peripheral whole blood is associated with favorable
      prognosis in advanced non-small cell lung cancer patients.
AB  - Polycomb group member protein BMI1 is involved in maintaining cell identity,
      proliferation, differentiation and human oncogenesis. In the present study, we
      determined BMI1 mRNA expression in whole blood and evaluated the impact of the
      expression level on the treatment response and survival of 96 advanced NSCLC
      patients treated with first-line platinum-based chemotherapy. We also determined
      BMI1 mRNA expression in primary tumors from 22 operable NSCLC patients treated
      with radical surgery. We found that compared with control subjects, BMI1 mRNA
      expression in whole blood of advanced NSCLC patients was decreased (P<0.001).
      Similarly, we observed decreased BMI1 mRNA expression in primary tumors compared
      to normal lungs from operable NSCLC patients (P=0.001). We found high BMI1 mRNA
      expression in blood was associated with longer progression-free survival (PFS)
      (P=0.049) and overall survival (OS) (P=0.012) in advanced NSCLC patients treated
      with first-line platinum-based chemotherapy. However, no association between the
      BMI1 mRNA level and response to chemotherapy was found (P=0.21). Multivariate Cox
      proportional hazards regression analysis showed elevated BMI1 mRNA level in whole
      blood was an independent prognostic factor for longer PFS (P=0.012) and OS
      (P<0.001). In conclusion, BMI1 mRNA expression in whole blood might represent a
      new biomarker for the diagnosis and prognosis of NSCLC.

PMID- 28445988
TI  - Specific up-regulation of p21 by a small active RNA sequence suppresses human
      colorectal cancer growth.
AB  - The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth
      by stimulating the p21 gene expression. We focused our research of p21-saRNA-322
      on colorectal cancer because 1) p21 down-regulation is a signature abnormality of
      the cancer, and 2) colorectal cancer might be a suitable target for in situ p21
      saRNA-322 delivery. The goal of the present study is to learn the activity of p21
      saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT
      116, HCT-116 (p53-/-) and HT-29 were transfected with the p21-saRNA-322. The
      expression of P21 protein and p21 mRNA were measured using the Western blot and
      reverse transcriptase polymerase chain reaction (RT-PCR). The effect of p21-saRNA
      322 on cancer cells was evaluated in vitro; and furthermore, a xenograft
      colorectal tumor mode in mice was established to estimate the tumor suppressing
      ability of p21-saRNA-322 in vivo. The results showed that in all three colorectal
      cancer cell lines, the expression of p21 mRNA and P21 protein were dramatically
      elevated after p21-saRNA-322 transfection. Transfection of p21-saRNA-322 caused
      apoptosis and cell cycle arrest at the G0/G1. Furthermore, anti-proliferation
      effect, reduction of colonies formation and cell senescence were observed in p21
      saRNA-322 treated cells. Animal studies showed that p21-saRNA-322 treatment
      significantly inhibited the HT-29 tumor growth and facilitated p21 activation in
      vivo. These results indicated that, p21-saRNA-322-induceded up-regulation of p21
      might be a promising therapeutic option for the treatment of colorectal cancer.

PMID- 28445987
TI  - Context-dependent miR-204 and miR-211 affect the biological properties of
      amelanotic and melanotic melanoma cells.
AB  - Despite increasing amounts of experimental evidence depicting the involvement of
      non-coding RNAs in cancer, the study of BRAFV600E-regulated genes has thus far
      focused mainly on protein-coding ones. Here, we identify and study the microRNAs
      that BRAFV600E regulates through the ERK pathway.By performing small RNA
      sequencing on A375 melanoma cells and a vemurafenib-resistant clone that was
      taken as negative control, we discover miR-204 and miR-211 as the miRNAs most
      induced by vemurafenib. We also demonstrate that, although belonging to the same
      family, these two miRNAs have distinctive features. miR-204 is under the control
      of STAT3 and its expression is induced in amelanotic melanoma cells, where it
      acts as an effector of vemurafenib's anti-motility activity by targeting AP1S2.
      Conversely, miR-211, a known transcriptional target of MITF, is induced in
      melanotic melanoma cells, where it targets EDEM1 and consequently impairs the
      degradation of TYROSINASE (TYR) through the ER-associated degradation (ERAD)
      pathway. In doing so, miR-211 serves as an effector of vemurafenib's pro
      pigmentation activity. We also show that such an increase in pigmentation in turn
      represents an adaptive response that needs to be overcome using appropriate
      inhibitors in order to increase the efficacy of vemurafenib.In summary, we unveil
      the distinct and context-dependent activities exerted by miR-204 family members
      in melanoma cells. Our work challenges the widely accepted "same miRNA family =
      same function" rule and provides a rationale for a novel treatment strategy for
      melanotic melanomas that is based on the combination of ERK pathway inhibitors
      with pigmentation inhibitors.

PMID- 28445990
TI  - Prognostic value of tumor mutations in radically treated locally advanced non
      small cell lung cancer patients.
AB  - INTRODUCTION: Chemo-radiation is standard treatment in locally advanced non-small
      cell lung cancers (NSCLC). The prognostic value of mutations has been poorly
      explored in this population. RESULTS: Clinical data were collected from 190
      patients and mutational profiles were obtained in 78 of them; 58 (74%) were
      males, 31 (40%) current smokers, 47/31 stage IIIA/IIIB and 40 (51%)
      adenocarcinoma. The following mutations were identified: EGFR 12% (9/78), KRAS
      15% (12/78), BRAF 5% (3/65), PI3KCA 2% (1/57), NRAS 3% (1/32), and ALK+ (FISH) 4%
      (2/51). HER2 was not detected. Median follow-up was 3.1 years. Overall survival
      was evaluated by group; no significant differences were identified in median
      overall survival (p = 0.21), with 29.4 months for the EGFR/ALK group (n = 11),
      12.8 months for other mutations (n = 17), and 23.4 months for wild-type (n = 50).
      The EGFR/ALK and other mutations groups had poorer median progression-free
      survival (9.6 and 6.0 months) compared to the wild-type group (12.0 months;
      multivariate hazard ratio 2.0 [95% CI, 0.9-4.2] and 2.8 [95% CI, 1.5-5.2]
      respectively, p = 0.003). MATERIALS AND METHODS: We retrospectively reviewed all
      patients receiving radical treatment for locally advanced NSCLC in a single
      institution between January 2002 and June 2013. Next generation sequencing was
      performed on DNA from paraffin-embedded tissue. ALK rearrangements were detected
      by immunohistochemistry and/or FISH. Mutational prognostic value for Kaplan-Meier
      survival parameters was determined by log-rank tests and Cox proportional hazards
      models. CONCLUSIONS: Selected gene alterations may be associated with poorer
      progression-free survival in locally advanced radically treated NSCLC and their
      prognostic and/or predictive value merits further evaluation in a larger
      population.

PMID- 28445991
TI  - Human epidermal growth factor receptor 2 expression is more important than
      Bacillus Calmette Guerin treatment in predicting the outcome of T1G3 bladder
      cancer.
AB  - In the present study we tested the role of Human Epidermal Growth Factor Receptor
      2 (HER-2) expression, as assayed by immunohistochemistry, in predicting
      recurrence and progression in 67 patients with T1G3 BC having undergone
      transurethral resection of bladder tumor (TURBT) alone (33) or TURBT + Bacillus
      Calmette Guerin (BCG) instillations (34). All patients had a negative restaging
      TURBT within 4 months after the first TURBT. At median follow-up of 75.7 months,
      the overall disease-free and progression-free rates were 35.8% and 73.0%,
      respectively. Univariate Kaplan-Meier survival analysis showed that traditional
      prognostic factors (sex, tumor number/size/recurrence) failed to predict disease
      free and progression free survival (DFS, PFS). BCG treatment was a significant
      predictor of DFS (p=0.0231) but not of PFS (p=0.6901). HER-2 overexpression was a
      significant predictor of DFS (p=0.0013) and PFS (p=0.0322) in the overall
      patients population, but failed to predict PFS when patients were stratified for
      treatment (BCG: p=0.1290; no BCG: p=0.1696) probably due to the limited number of
      events. Multivariate Cox proportional-hazards regression analysis confirmed that
      BCG treatment was a significant predictor of DFS (p=0.012) but not of PFS
      (p=0.924), whereas HER-2 overexpression was a significant predictor of DFS
      (p=0.001) and PFS (p=0.041). These findings suggest that HER-2 status performs
      better than "traditional" prognostic factors as well as of BCG treatment in
      predicting the outcome of T1G3 BC, thus providing grounds for further testing
      this marker and possibly incorporating it in a panel of molecular markers that
      could reliably predict the behavior of this challenging disease.

PMID- 28445989
TI  - TMPRSS2:ERG gene fusion variants induce TGF-beta signaling and epithelial to
      mesenchymal transition in human prostate cancer cells.
AB  - TMPRSS2:ERG (T/E) gene fusions are present in approximately 50% of all prostate
      cancer (PCa) cases. The expression of fusion mRNAs from distinct T/E variants is
      associated with clinicopathological parameters, while the underlying molecular
      processes remain unclear. We characterized the molecular mechanisms and
      functional implications caused by doxycycline (Dox)-inducible overexpression of
      the frequent T/E III and VI fusion variants in LNCaP cells. Induction of T/E
      expression resulted in increased cellular migratory and invasive potential, and
      reduced proliferation and accumulation in G1 phase. T/E overexpressing cells
      showed epithelial-to-mesenchymal transition (EMT), as demonstrated by
      upregulation of TGF-beta and WNT pathway genes, mesenchymal markers, and
      increased phosphorylation of the p38 MAPK. Augmented secretion of TGF-beta1 and 
      beta2, and T/E-mediated regulation of ALK1, a member of the TGF-beta receptor
      family, was detected. ALK1 inhibition in T/E overexpressing cells blocked p38
      phosphorylation and reduced the expression of the TGF-beta target genes VIM,
      MMP1, CDH2, and SNAI2. We found a T/E variant VI-specific induction of miR-503
      associated with reduced expression of SMAD7 and CDH1. Overexpression of miR-503
      led to increased levels of VIM and MMP1. Our findings indicate that TGF-beta
      signaling is a major determinant of EMT in T/E overexpressing LNCaP cells. We
      provide evidence that T/E VI-specific transcriptional modulation by miR-503
      accounts for differences in the activation of EMT pathway genes, promoting the
      aggressive phenotype of tumors expressing T/E variant VI. We suggest that ALK1
      mediated TGF-beta signaling is a novel oncogenic mechanism in T/E positive PCa.

PMID- 28445994
TI  - Correction: Amphiregulin enhances alpha6beta1 integrin expression and cell
      motility in human chondrosarcoma cells through Ras/Raf/MEK/ERK/AP-1 pathway.

PMID- 28445993
TI  - Berberine nanoparticles protects tubular epithelial cells from renal ischemia
      reperfusion injury.
AB  - Renal ischemia-reperfusion (I/R) injury is one of the most common causes of acute
      renal failure, the prognosis of which remains poor and there still lacks of
      effective therapeutics available in the clinic. This study aimed at investigating
      the effects of Berberine nanoparticles (BBR-NP) on the ischemia-reperfusion
      injury of renal tubular epithelial cells and underlying the mechanisms. Our
      results showed that in a rat model of renal I/R injury, BBR and BBR-NP protected
      renal against injury both functionally (as assessed by serum urea nitrogen and
      creatinine level) and morphologically (as assessed by HE staining, transmission
      electron microscopy and TUNEL staining) in a dose-dependent manner, with the
      effects of BBR-NP superior to BBR alone. Mechanism investigation showed that BBR
      NP reversed oxidative stress and subsequent apoptosis of renal cells, as
      demonstrated by the decreased expression of proteins involved in the oxidative
      stress and mitochondrial stress pathways. In conclusion, our study showed that
      BBR-NP is superior to BBR alone in protecting renal against I/R injury and
      explored the underlying mechanisms, which should be tested in further studies and
      might give impetus to the development of novel therapeutics based on BBR-NP
      against renal I/R.

PMID- 28445992
TI  - Interaction between the estrogen receptor and fibroblast growth factor receptor
      pathways in non-small cell lung cancer.
AB  - The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC)
      proliferation. Since fibroblast growth factors (FGFs) are known regulators of
      stem cell markers in ER positive breast cancer, we investigated whether a link
      between the ER, FGFs, and stem cell markers exists in NSCLC. In lung
      preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen
      fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9
      secretion, and reduced expression of the stem cell markers SOX2 and nanog. Mice
      administered beta-estradiol during carcinogen exposure showed increased FGF2,
      FGF9, SOX2, and Nanog expression in airway preneoplasias. In normal FGFR1 copy
      number NSCLC cell lines, multiple FGFR receptors were expressed and secreted
      several FGFs. beta-estradiol caused enhanced FGF2 release, which was blocked by
      fulvestrant. Upon co-inhibition of ER and FGFRs using fulvestrant and the pan
      FGFR inhibitor AZD4547, phosphorylation of FRS2, the FGFR docking protein, was
      maximally reduced, and enhanced anti-proliferative effects were observed.
      Combined AZD4547 and fulvestrant enhanced lung tumor xenograft growth inhibition
      and decreased Ki67 and stem cell marker expression. To verify a link between
      ERbeta, the predominant ER in NSCLC, and FGFR signaling in patient tumors, mRNA
      analysis was performed comparing high versus low ERbeta expressing tumors. The
      top differentially expressed genes in high ERbeta tumors involved FGF signaling
      and human embryonic stem cell pluripotency. These results suggest interaction
      between the ER and FGFR pathways in NSCLC promotes a stem-like state. Combined
      FGFR and ER inhibition may increase the efficacy of FGFR inhibitors for NSCLC
      patients lacking FGFR genetic alterations.

PMID- 28445995
TI  - Microstructure of Spark Plasma-Sintered Silicon Nitride Ceramics.
AB  - The microstructure and phase composition of the high-content Al2O3-Y2O3-doped
      spark plasma-sintered silicon nitride were investigated. Fully dense silicon
      nitride ceramics with a typical alpha-Si3N4 equiaxed structure with average grain
      size from 200 to 530 nm, high elastic modulus of 288 GPa, and high hardness of
      2038 HV were spark plasma sintered (SPSed) at 1550  degrees C. Silicon nitride
      with elongated beta-Si3N4 grains, higher hardness of 1800 HV, density of 3.25
      g/cm3, and Young's modulus 300 GPa SPSed at 1650  degrees C was also reviewed.

PMID- 28445996
TI  - Energy Transfer in Ce0.85Tb0.15F3 Nanoparticles-CTAB Shell-Chlorin e6 System.
AB  - Formation and electronic excitation energy transfer process in the nanosystem
      consisting of Ce0.85Tb0.15F3 nanoparticles, cetrimonium bromide (CTAB)
      surfactant, and chlorin e6 photosensitizer were studied. It was shown that
      chlorin e6 molecules bind to Ce0.85Tb0.15F3 NP in the presence of CTAB forming
      thus Ce0.85Tb0.15F3 NP-CTAB-chlorin e6 nanosystem. We consider that binding
      occurs via chlorin e6 embedding in the shell of CTAB molecules, formed around NP.
      In the Ce0.85Tb0.15F3 NP-CTAB-chlorin e6 nanosystem, electronic excitation energy
      transfer from Ce3+ to chlorin e6 takes place both directly (with the 0.33
      efficiency for 2 MUM chlorin e6) and via Tb3+.

PMID- 28445997
TI  - Using Metal-Multilayer-Dielectric Structure to Increase Sensitivity of Surface
      Plasmon Resonance Sensor.
AB  - We propose using a specially designed metal-multilayer-dielectric structure
      deposited on glass substrate to enhance the evanescent field and improve the
      sensitivity of the surface plasmon resonance sensor. The proposed structure
      supports both hybrid plasmonic transverse magnetic modes and conventional
      waveguide transverse electric modes. We show numerically the significant
      enhancement of the evanescent field and improvement of the sensitivity for the
      waveguide transverse electric mode.

PMID- 28445998
TI  - Infrared, Raman and Magnetic Resonance Spectroscopic Study of SiO2:C Nanopowders.
AB  - Optical and magnetic properties of SiO2:C nanopowders obtained by chemical and
      thermal modification of fumed silica were studied by Fourier transform infrared
      spectroscopy, Raman, continuous wave (CW) electron paramagnetic resonance (EPR),
      echo-detected EPR and pulsed electron nuclear double resonance (ENDOR)
      spectroscopy. Two overlapping signals of Lorentzian lineshape were detected in CW
      EPR spectra of the initial SiO2:C. The EPR signal at g = 2.0055(3) is due to the
      silicon dangling bonds, which vanishes after thermal annealing, and the second
      EPR signal at g = 2.0033(3) was attributed to the carbon-related defect (CRD).
      The annealing of the SiO2:C samples gives rise to the increase of the CRD spin
      density and shift to the higher g-values due to the appearance of the oxygen in
      the vicinity of the CRD. Based on the temperature-dependent behavior of the CRD
      EPR signal intensity, linewidth and resonance field position we have attributed
      it to the spin system with non-localized electrons hopping between neighboring
      carbon dangling bonds, which undergo a strong exchange interaction with a
      localized spin system of carbon nanodots. The observed motional narrowing of the
      CRD EPR signal in the temperature interval from 4 to 20 K indicates that
      electrons are mobile at 4 K which can be explained by a quantum character of the
      conductivity in the vicinity of the carbon layer. The electrons trapped in
      quantum wells move from one carbon nanodot to another by hopping process through
      the energy barrier. The fact that echo-detected EPR signal at g = 2.0035(3) was
      observed in SiO2:C sample annealed at T ann >= 700  degrees C serves as evidence
      that non-localized electrons coexist with localized electrons that have the
      superhyperfine interaction with surrounding 13C and 29Si nuclei located at the
      SiO2:C interface. The presence of the superhyperfine interaction of CRD with 1H
      nuclei indicates the existence of hydrogenated regions in SiO2:C sample.

PMID- 28445999
TI  - Crystal Orientation Effect on the Subsurface Deformation of Monocrystalline
      Germanium in Nanometric Cutting.
AB  - Molecular dynamics simulations of nanometric cutting on monocrystalline germanium
      are conducted to investigate the subsurface deformation during and after
      nanometric cutting. The continuous random network model of amorphous germanium is
      established by molecular dynamics simulation, and its characteristic parameters
      are extracted to compare with those of the machined deformed layer. The
      coordination number distribution and radial distribution function (RDF) show that
      the machined surface presents the similar amorphous state. The anisotropic
      subsurface deformation is studied by nanometric cutting on the (010), (101), and
      (111) crystal planes of germanium, respectively. The deformed structures are
      prone to extend along the 110 slip system, which leads to the difference in the
      shape and thickness of the deformed layer on various directions and crystal
      planes. On machined surface, the greater thickness of subsurface deformed layer
      induces the greater surface recovery height. In order to get the critical
      thickness limit of deformed layer on machined surface of germanium, the optimized
      cutting direction on each crystal plane is suggested according to the relevance
      of the nanometric cutting to the nanoindentation.

PMID- 28446000
TI  - Structural Modification of Single-Layer Graphene Under Laser Irradiation Featured
      by Micro-Raman Spectroscopy.
AB  - Confocal micro-Raman spectroscopy is used as a sensitive tool to study the nature
      of laser-induced defects in single-layer graphene. Appearance and drastic
      intensity increase of D- and D' modes in the Raman spectra at high power of laser
      irradiation is related to generation of structural defects. Time- and power
      dependent evolution of Raman spectra is studied. The dependence of relative
      intensity of defective D- and D' bands is analyzed to relate the certain types of
      structural defects. The surface density of structural defects is estimated from
      the intensity ratio of D- and G bands using the D-band activation model. Unusual
      broadening of the D band and splitting of the G band into G- and G+ components
      with redistribution of their intensities is observed at high laser power and
      exposition. Position of the G+ band is discussed in relation with nonuniform
      doping of graphene with charge impurities. Simultaneous presence in the Raman
      spectra of heavily irradiated graphene of rather narrow G band and broaden D band
      is explained by coexistence within the Raman probe of more and less damaged
      graphene areas. This assumption is additionally confirmed by confocal Raman
      mapping of the heavily irradiated area.

PMID- 28446001
TI  - A post-genome-wide association study validating the association of the
      glycophorin C gene with serum hemoglobin level in pig.
AB  - OBJECTIVE: This study aimed to validate the statistical evidence from the genome
      wide association study (GWAS) as true-positive and to better understand the
      effects of the glycophorin C (GYPC) gene on serum hemoglobin traits. METHODS: Our
      initial GWAS revealed the presence of two single nucleotide polymorphisms (SNPs)
      (ASGA0069038 and ALGA0084612) for the hemoglobin concentration trait (HGB) in the
      2.48 Mb region of SSC15. From this target region, GYPC was selected as a
      promising gene that associated with serum HGB traits in pigs. SNPs within the
      GYPC gene were detected by sequencing. Thereafter, we performed association
      analysis of the variant with the serum hemoglobin level in three pig populations.
      RESULTS: We identified one SNP (g.29625094 T>C) in exon 3 of the GYPC gene.
      Statistical analysis showed a significant association of the SNP with the serum
      hemoglobin level on day 20 (p<0.05). By quantitative real-time polymerase chain
      reaction, the GYPC gene was expressed in eight different tissues. CONCLUSION:
      These results might improve our understanding of GYPC function and provide
      evidence for its association with serum hemoglobin traits in the pig. These
      results also indicate that the GYPC gene might serve as a useful marker in pig
      breeding programs.

PMID- 28446002
TI  - Effects of fungal (Lentinussajor-caju) treated oil palm frond on performance and
      carcass characteristics in finishing goats.
AB  - OBJECTIVE: This experiment was conducted to investigate the effects of fungal
      treated oil palm fronds (FTOPF) on performance, carcass traits, meat quality, and
      muscle chemical composition. METHODS: Eighteen growing crossbred male goats (Thai
      Native*Anglo Nubian) with 18.7+/-2.0 kg of initial body weight (BW) were
      stratified and blocked by BW in a randomized complete block design. Three diets
      containing 30% of oil palm fronds (OPF) either untreated (UOPF) or treated with
      Lentinussajor-caju (FTOPF) with or without urea (FTOPFU) were used as roughage
      sources in total mixed rations (TMRs). The diets were offered ad libitum and
      weight gain was determined. At the end of the experimental period, the harvest
      data and carcass characteristics of the goats were recorded, and muscular
      longissimus dorsi composition was determined. RESULTS: No significant effect of
      fungal treated (FT) inclusion was observed in any of the feed intake, growth
      performance, and carcass characteristics. Likewise, no apparent effects on
      carcass composition and muscle chemical composition were detected in this study,
      except for hind leg and chump were affected (p<0.05) by FT inclusion. CONCLUSION:
      In conclusion, feeding of fungal (Lentinussajor-caju) treated oil palm frond in
      TMR diet did not affect performance and carcass characteristics in finishing
      goats.

PMID- 28446003
TI  - Effects of Canine and Murine Mesenchymal Stromal Cell Transplantation on
      Peripheral Nerve Regeneration.
AB  - Background and Objectives: Maintaining a permissive microenvironment is essential
      for adequate nerve regeneration. Cell-based therapy has the potential based cell
      replacement and promotion of axonal growth. The adipose tissue derived
      mesenchymal stromal cells (Ad-MSC) attract interest because neuroregenerative and
      anti-inflammatory properties. The aim of this study was to evaluate the effects
      of canine and murine Ad-MSC transplantation on the sciatic nerve regeneration.
      Methods: Forty Wistar rats were divided randomly into: control group - CG (n=8);
      denervated group - DG (n=8); decellularized vein group - VG (n=8); decellularized
      vein+canine MSC-cMSC (n=8); descellularized vein+murine MSC-mMSC (n=8). After 10
      mm nerve gap, the tubulation technique was performed with decellularized vein
      filled with 106 MSC labeled with quantum dots (Qtracker 665(r)). The sciatic
      nerve functional index (SFI) and electroneuromyography (ENMG) measurements were
      carried and morphometric and immunohistochemistry analysis of the tissue.
      Results: The SFI values were higher in the cMSC and mMSC groups at day 27
      (p<0.020) and day 35 (p<0.011). The ENMG analysis also revealed better results in
      the mMSC group. Density, number, and total area of the fibers were increased in
      the mMSC and cMSC groups. Brain-derived neurotrophic factor BDNF and S-100
      protein positive immunoreactivity showed a higher expression for both in the
      nerve of the mMSC and cMSC groups. The MSC labeled with quantum dots were
      detected at day 35, indicating neuronal survival long after the nerve damage.
      Conclusions: Murine and canine Ad-MSC associated with decellularized vein
      scaffold had positive effects on sciatic nerve regeneration in rats.

PMID- 28446005
TI  - Cardioprotective Effects of Wharton Jelly Derived Mesenchymal Stem Cell
      Transplantation in a Rodent Model of Myocardial Injury.
AB  - Background: Whartons jelly-derived mesenchymal stem cells are a valuable
      alternative source that possess multipotent properties, easy to obtain and
      available in large scale compared to BMMSCs. We investigated the possibility of
      cardiac function improvement post isoproterenol induced cardiac injury in a rat
      model following human WJMSCs transplantation. Materials and Methods: MSCs were
      extracted and cultured from cord WJ, characterized by morphology,
      Immunophenotyping and differentiation to osteoblast and adipocytes. WJMSCs were
      labeled with PKH2 linker dye. Wistar rats were divided into control group, ISO
      group (injected with 2 doses of isoproterenol) to induce myocardial injury and
      ISO group transplanted with labelled WJMSCs. ECG, electrocardiographic patterns,
      cardiac marker enzymes, tracing of labeled MSCs and immunohistochemical analysis
      of myocardial cryosections were studied. Results and Conclusions: WJ derived MSCs
      were expanded for more than 14 passages while maintaining their undifferentiated
      state, were positive for MSC markers and were able to differentiate into
      adipocyte and osteoblast. We demonstrated that intravenously administered WJMSCs
      were capable of homing predominently in the ischemic myocardium. Cardiac markers
      were positively altered in stem cell treated group compared to ISO group. ECG and
      ECHO changes were improved with higher survival rate. WJMSCs could differentiate
      into cardiac-like cells (positive for cardiac specific proteins) in vivo. WJMSCs
      infusion promoted cardiac protection and reduced mortality, emphasizing a
      promising therapeutic role for myocardial insufficiency.

PMID- 28446004
TI  - Conditioned Medium Derived from Salidroside-Pretreated Mesenchymal Stem Cell
      Culture Ameliorates Mouse Lipopolysaccharide-Induced Cerebral Neuroinflammation-
      Histological and Immunohistochemical Study.
AB  - Background and Objectives: Neuroinflammation is involved in the pathogenesis of
      neurodegenerative disorders. Conditioned medium (CM) derived from bone marrow
      mesenchymal stem cells (MSCs) revealed substantial benefits due to its rich
      content of trophic factors. Salidroside (Sal), extracted from Rhodiola rosea, is
      known for its anti-inflammatory and neuroprotective effects. This study was
      designed to investigate the effect of Sal pretreated CM (CM-Sal) derived from
      bone marrow MSCs in lipopolysaccharide (LPS) induced neuroinflammation. Material
      and Methods: Fifty adult male mice were equally divided into 5 groups: Group I
      (Normal Control), Group II (LPS): single 0.8 mg/kg LPS intraperitoneally; Group
      III (LPS-DMEM), Group IV (LPS-CM) and Group V (LPS-CM-Sal): LPS was injected as
      group II followed, 24 hours later, by intranasal injection of 50 MUl of filtered
      serum- free Dulbecco's Modified Eagle's medium (DMEM), CM or CM-Sal,
      respectively, twice daily for 4 days. Animals were sacrificed at day 6 and
      paraffin cerebral sections were subjected to Hematoxylin and Eosin staining and
      immunohistochemistry with caspase 3 (apoptosis), glial fibrillary acidic protein
      GFAP (astrocytes) and CD68 (active microglia) followed by quantitative
      morphometric study. Results: Examination of LPS and LPS-DMEM groups revealed
      neuronal apoptosis with reactive astrogliosis and increased active microglia. LPS
      CM and LPS-CM-Sal groups showed less apoptosis, less astrocytes and less active
      microglia. The regression in neuroinflammation was more evident in LPS-CM-Sal
      group and the difference was statistically significant compared to other groups.
      Conclusion: CM-Sal derived from MSCs culture elicited significant
      histopathological improvement in LPS induced neuroinflammation which could be
      used as new therapeutic modality.

PMID- 28446006
TI  - Trending Speculations of Tumor-Initiating Cells in Squamous Cell Cancers of Head
      and Neck.
AB  - Tumor-initiating cells are a diminutive subpopulation of stem cells that have
      ability of long term self-renewal and generation of varied traits of tumor cell
      population. Understanding the concept of tumor-initiating cells may have a great
      implicative intimation for our comprehension of cancer pathobiology and for the
      delineation of new therapies directed towards these stem cells. The present
      review is an endeavor to conceptualize the role of tumor-initiating cells in the
      Squamous Cell Cancers (SCC) of head and neck, their role in tumorigenesis and the
      possible supplementary approach in the latest treatment modalities.

PMID- 28446007
TI  - Collaborative Efforts Among the Fields of Technology, Device Development, and
      Medicine.

PMID- 28446008
TI  - New Equipment and Devices for Therapeutic Purpose.

PMID- 28446009
TI  - Applications of Microfluidic Devices for Urology.
AB  - Microfluidics is considered an important technology that is suitable for numerous
      biomedical applications, including cancer diagnosis, metastasis, drug delivery,
      and tissue engineering. Although microfluidics is still considered to be a new
      approach in urological research, several pioneering studies have been reported in
      recent years. In this paper, we reviewed urological research works using
      microfluidic devices. Microfluidic devices were used for the detection of
      prostate and bladder cancer and the characterization of cancer microenvironments.
      The potential applications of microfluidics in urinary analysis and sperm sorting
      were demonstrated. The use of microfluidic devices in urology research can
      provide high-throughput, high-precision, and low-cost analyzing platforms.

PMID- 28446010
TI  - Development of Decision Support Formulas for the Prediction of Bladder Outlet
      Obstruction and Prostatic Surgery in Patients With Lower Urinary Tract
      Symptom/Benign Prostatic Hyperplasia: Part I, Development of the Formula and its
      Internal Validation.
AB  - PURPOSE: As the elderly population increases, a growing number of patients have
      lower urinary tract symptom (LUTS)/benign prostatic hyperplasia (BPH). The aim of
      this study was to develop decision support formulas and nomograms for the
      prediction of bladder outlet obstruction (BOO) and for BOO-related surgical
      decision-making, and to validate them in patients with LUTS/BPH. METHODS: Patient
      with LUTS/BPH between October 2004 and May 2014 were enrolled as a development
      cohort. The available variables included age, International Prostate Symptom
      Score, free uroflowmetry, postvoid residual volume, total prostate volume, and
      the results of a pressure-flow study. A causal Bayesian network analysis was used
      to identify relevant parameters. Using multivariate logistic regression analysis,
      formulas were developed to calculate the probabilities of having BOO and
      requiring prostatic surgery. Patients between June 2014 and December 2015 were
      prospectively enrolled for internal validation. Receiver operating characteristic
      curve analysis, calibration plots, and decision curve analysis were performed.
      RESULTS: A total of 1,179 male patients with LUTS/BPH, with a mean age of 66.1
      years, were included as a development cohort. Another 253 patients were enrolled
      as an internal validation cohort. Using multivariate logistic regression
      analysis, 2 and 4 formulas were established to estimate the probabilities of
      having BOO and requiring prostatic surgery, respectively. Our analysis of the
      predictive accuracy of the model revealed area under the curve values of 0.82 for
      BOO and 0.87 for prostatic surgery. The sensitivity and specificity were 53.6%
      and 87.0% for BOO, and 91.6% and 50.0% for prostatic surgery, respectively. The
      calibration plot indicated that these prediction models showed a good
      correspondence. In addition, the decision curve analysis showed a high net
      benefit across the entire spectrum of probability thresholds. CONCLUSIONS: We
      established nomograms for the prediction of BOO and BOO-related prostatic surgery
      in patients with LUTS/BPH. Internal validation of the nomograms demonstrated that
      they predicted both having BOO and requiring prostatic surgery very well.

PMID- 28446011
TI  - Development of Decision Support Formulas for the Prediction of Bladder Outlet
      Obstruction and Prostatic Surgery in Patients With Lower Urinary Tract
      Symptom/Benign Prostatic Hyperplasia: Part II, External Validation and Usability
      Testing of a Smartphone App.
AB  - PURPOSE: We aimed to externally validate the prediction model we developed for
      having bladder outlet obstruction (BOO) and requiring prostatic surgery using 2
      independent data sets from tertiary referral centers, and also aimed to validate
      a mobile app for using this model through usability testing. METHODS: Formulas
      and nomograms predicting whether a subject has BOO and needs prostatic surgery
      were validated with an external validation cohort from Seoul National University
      Bundang Hospital and Seoul Metropolitan Government-Seoul National University
      Boramae Medical Center between January 2004 and April 2015. A smartphone-based
      app was developed, and 8 young urologists were enrolled for usability testing to
      identify any human factor issues of the app. RESULTS: A total of 642 patients
      were included in the external validation cohort. No significant differences were
      found in the baseline characteristics of major parameters between the original
      (n=1,179) and the external validation cohort, except for the maximal flow rate.
      Predictions of requiring prostatic surgery in the validation cohort showed a
      sensitivity of 80.6%, a specificity of 73.2%, a positive predictive value of
      49.7%, and a negative predictive value of 92.0%, and area under receiver
      operating curve of 0.84. The calibration plot indicated that the predictions have
      good correspondence. The decision curve showed also a high net benefit. Similar
      evaluation results using the external validation cohort were seen in the
      predictions of having BOO. Overall results of the usability test demonstrated
      that the app was user-friendly with no major human factor issues. CONCLUSIONS:
      External validation of these newly developed a prediction model demonstrated a
      moderate level of discrimination, adequate calibration, and high net benefit
      gains for predicting both having BOO and requiring prostatic surgery. Also a
      smartphone app implementing the prediction model was user-friendly with no major
      human factor issue.

PMID- 28446012
TI  - Differentiation Potential of Mesenchymal Stem Cells Is Related to Their Intrinsic
      Mechanical Properties.
AB  - PURPOSE: The differentiation properties of stem cells are not yet fully
      understood due to their close association with multiple environmental and
      extrinsic factors. This study investigates the differentiation properties of
      mesenchymal stem cells (MSCs) and correlates them with their intrinsic mechanical
      properties. METHODS: A total of 3 different types of MSCs, namely bone marrow
      derived MSCs (BMSCs), umbilical cord-derived MSCs (UCSCs), and adipose-derived
      MSCs (ADSCs) were evaluated. These 3 MSCs were individually differentiated into
      adipocytes and osteoblasts for 3 weeks. The mechanical properties of the MSCs and
      differentiated cells were determined by atomic force microscopy. RESULTS: ADSCs
      showed the greatest ability to differentiate into adipocytes, followed by BMSCs
      and UCSCs. While UCSCs differentiated readily into osteoblasts, BMSCs and ADSCs
      were less likely to undergo this differentiation. UCSCs were the "hardest" cells,
      while ADSCs were the "softest." The cells differentiated from "hard" MSCs were
      stiffer than the cells differentiated from "soft" MSCs, irrespective of lineage
      specification. CONCLUSIONS: The differentiation ability of MSCs and the
      mechanical properties of the differentiated cells were closely linked. However,
      there were no significant correlations regarding changes in the mechanical
      properties between the nuclear region and the cytoplasm during differentiation.

PMID- 28446013
TI  - The In Vivo Effect of Ytterbium-Doped Fiber Laser on Rat Buccal Mucosa as a
      Simulation of Its Effect on the Urinary Tract: A Preclinical Histopathological
      Evaluation.
AB  - PURPOSE: The aim of this study was to perform a histological analysis of the
      effect of a ytterbium-doped fiber (YDF) laser on oral buccal mucosa tissue in
      vivo to simulate its effect on the mucosa of the lower urinary tract. METHODS: A
      total of 90 8-week-old Sprague-Dawley rats were anesthetized with urethrane (1.2
      g/kg intraperitoneally). A prespecified inner buccal mucosal site was irradiated
      with a YDF master-oscillator power amplifier (MOPA) system for 60 seconds, with
      output power settings of 0.5, 1, and 2 W, respectively, in 3 treatment groups.
      Specimens of irradiated tissue were harvested at 2 hours, 24 hours, 2 weeks, and
      4 weeks after irradiation. The tissue specimens were stained with hematoxylin and
      eosin for histological analysis. RESULTS: In the group treated with 0.5 W, basal
      cell elongation and vacuolization were observed at 2 hours and 24 hours after
      treatment, respectively. No evident injury was observed after 2 or 4 weeks. The
      group treated with 1 W presented partial basal layer separation, and even
      complete epidermal ablation, within 2 hours. At 24 hours after laser treatment,
      new capillaries on an edematous background of fibroblasts and myofibroblasts, as
      well as profuse infiltration of the neutrophils to the basal layer, were
      observed. Collagen deposition and reepithelization were observed in specimens
      taken 2 weeks and 4 weeks after treatment. The group treated with 2 W presented
      bigger and deeper injuries at 2 hours after irradiation. Meanwhile, subepidermal
      bullae with full-thickness epidermal necrosis and underlying inflammatory
      infiltrate were observed 24 hours after treatment. The presence of fibrous
      connective tissue and collagen deposition were observed 2 weeks and 4 weeks after
      the treatment. CONCLUSIONS: To our knowledge, this is the first report regarding
      the effect of a YDF laser on living tissue. Our study demonstrated that the
      typical histological findings of the tissue reaction to the YDF MOPA apparatus
      were very similar to those associated with thermal injuries. The extent and
      degree of tissue damage increased proportionally to the output power.

PMID- 28446014
TI  - Noninvasive Medical Tools for Evaluating Voiding Pattern in Real Life.
AB  - Voiding dysfunction is a common disease that contributes to a lower quality of
      life and has an increased prevalence in the elderly population. Noninvasive and
      objective methods such as uroflowmetry (UFM) and voiding diaries (VDs) are
      essential for exact diagnosis and effective treatment of this condition because
      patients with different causes of voiding dysfunction can complain of the same
      lower urinary tract symptoms. Further, different treatment options can be
      determined based on the diagnosis made from these symptoms. In order to improve
      the quality of UFM and VDs and to provide a convenient testing environment,
      several advances have been made by previous investigators. In this study, we
      investigate the history and technological mechanisms of UFM and VDs. We also aim
      to review UFM from the viewpoint of clinical and at-home uses, including the
      recently proposed toilet-shaped UFM and electronic VDs.

PMID- 28446015
TI  - Realistic Electric Field Mapping of Anisotropic Muscle During Electrical
      Stimulation Using a Combination of Water Diffusion Tensor and Electrical
      Conductivity.
AB  - PURPOSE: To realistically map the electric fields of biological tissues using a
      diffusion tensor magnetic resonance electrical impedance tomography (DT-MREIT)
      method to estimate tissue response during electrical stimulation. METHODS:
      Imaging experiments were performed using chunks of bovine muscle. Two silver wire
      electrodes were positioned inside the muscle tissue for electrical stimulation.
      Electric pulses were applied with a 100-V amplitude and 100-MUs width using a
      voltage stimulator. During electrical stimulation, we collected DT-MREIT data
      from a 3T magnetic resonance imaging scanner. We adopted the projected current
      density method to calculate the electric field. Based on the relation between the
      water diffusion tensor and the conductivity tensor, we computed the position
      dependent scale factor using the measured magnetic flux density data. Then, a
      final conductivity tensor map was reconstructed using the multiplication of the
      water diffusion tensor and the scale factor. RESULTS: The current density images
      from DT-MREIT data represent the internal current flows that exist not only in
      the electrodes but also in surrounding regions. The reconstructed electric filed
      map from our anisotropic conductivity tensor with the projected current density
      shows coverage that is more than 2 times as wide, and higher signals in both the
      electrodes and surrounding tissues, than the previous isotropic method owing to
      the consideration of tissue anisotropy. CONCLUSIONS: An electric field map
      obtained by an anisotropic reconstruction method showed different patterns from
      the results of the previous isotropic reconstruction method. Since accurate
      electric field mapping is important to correctly estimate the coverage of the
      electrical treatment, future studies should include more rigorous validations of
      the new method through in vivo and in situ experiments.

PMID- 28446016
TI  - Biodegradation and Biocompatibility of Poly L-lactic Acid Implantable Mesh.
AB  - PURPOSE: The purpose of this study was to evaluate the biodegradation and
      biocompatibility of poly L-lactic acid (PLLA) implantable mesh under in vitro and
      in vivo conditions. METHODS: PLLA mesh was examined for changes in weight and
      tensile strength. The histology of the tissue around the PLLA implant was also
      evaluated. RESULTS: The weight and tensile strength of the PLLA prosthesis was
      stable for 180 days. In addition, the surface of the PLLA mesh was not digested
      under in vitro or in vivo conditions as determined by scanning electron
      microscope. Histologically, there were no significant changes in the diameters of
      implanted PLLA mesh and subtype fibers over the course of 180 days. Likewise,
      there were no significant changes in the number of inflammatory and mast cells
      after 180 days, nor was there an increase in the percentage of collagen
      surrounding the PLLA mesh. CONCLUSIONS: The results indicate that PLLA prostheses
      have good rigidity and biocompatibility in vivo and in vitro.

PMID- 28446017
TI  - Dexmedetomidine Oral Mucosa Patch for Sedation Suppresses Apoptosis in
      Hippocampus of Normal Rats.
AB  - PURPOSE: Dexmedetomidine, an alpha2-adrenergic agonist, provides sedative and
      analgesic effects without significant respiratory depression. Dexmedetomidine has
      been suggested to have an antiapoptotic effect in response to various brain
      insults. We developed an oral mucosa patch using dexmedetomidine for sedation.
      The effects of the dexmedetomidine oral mucosa patch on cell proliferation and
      apoptosis in the hippocampus were evaluated. METHODS: A hydrogel oral mucosa
      patch was adhered onto the oral cavity of physiologically normal rats, and was
      attached for 2 hours, 6 hours, 12 hours, or 24 hours. Plasma dexmedetomidine
      concentrations were determined by liquid chromatography- electrospray ionization
      tandem mass spectrometry-multiple-ion reaction monitoring (LC-ESI-MS/MS-MRM).
      Cell proliferation in the hippocampus was detected by Ki-67 immunohistochemistry.
      Caspase-3 immunohistochemistry, terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling staining, and Western blotting for Bax and Bcl-2 were
      performed to detect hippocampal apoptosis. The levels of brain-derived
      neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the hippocampus were
      also measured by Western blotting. RESULTS: Plasma dexmedetomidine concentration
      increased according to the attachment time of the dexmedetomidine oral mucosa
      patch. Hippocampal cell proliferation did not change due to the dexmedetomidine
      oral mucosa patch, and the dexmedetomidine oral mucosa patch exerted no
      significant effect on BDNF or TrkB expression. In contrast, the dexmedetomidine
      oral mucosa patch exerted an antiapoptotic effect depending on the attachment
      time of the dexmedetomidine oral mucosa patch. CONCLUSIONS: A dexmedetomidine
      oral mucosa patch can be used as a convenient tool for sedation, and is of
      therapeutic value due to its antiapoptotic effects under normal conditions.

PMID- 28446018
TI  - Development of Personalized Urination Recognition Technology Using Smart Bands.
AB  - PURPOSE: This study collected and analyzed activity data sensed through smart
      bands worn by patients in order to resolve the clinical issues posed by using
      voiding charts. By developing a smart band-based algorithm for recognizing
      urination activity in patients, this study aimed to explore the feasibility of
      urination monitoring systems. METHODS: This study aimed to develop an algorithm
      that recognizes urination based on a patient's posture and changes in posture.
      Motion data was obtained from a smart band on the arm. An algorithm that
      recognizes the 3 stages of urination (forward movement, urination, backward
      movement) was developed based on data collected from a 3-axis accelerometer and
      from tilt angle data. Real-time data were acquired from the smart band, and for
      data corresponding to a certain duration, the absolute value of the signals was
      calculated and then compared with the set threshold value to determine the
      occurrence of vibration signals. In feature extraction, the most essential
      information describing each pattern was identified after analyzing the
      characteristics of the data. The results of the feature extraction process were
      sorted using a classifier to detect urination. RESULTS: An experiment was carried
      out to assess the performance of the recognition technology proposed in this
      study. The final accuracy of the algorithm was calculated based on clinical
      guidelines for urologists. The experiment showed a high average accuracy of
      90.4%, proving the robustness of the proposed algorithm. CONCLUSIONS: The
      proposed urination recognition technology draws on acceleration data and tilt
      angle data collected via a smart band; these data were then analyzed using a
      classifier after comparative analyses with standardized feature patterns.

PMID- 28446019
TI  - Fusion Bead Procedure for Nuclear Forensics Employing Synthetic Enstatite to
      Dissolve Uraniferous and Other Challenging Materials Prior to Laser Ablation
      Inductively Coupled Plasma Mass Spectrometry.
AB  - There is an increasing demand for rapid and effective analytical tools to support
      nuclear forensic investigations of seized or suspect materials. Some methods are
      simply adapted from other scientific disciplines and can effectively be used to
      rapidly prepare complex materials for subsequent analysis. A novel sample fusion
      method is developed, tested, and validated to produce homogeneous, flux-free
      glass beads of geochemical reference materials (GRMs), uranium ores, and uranium
      ore concentrates (UOC) prior to the analysis of 14 rare earth elements (REE) via
      laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The
      novelty of the procedure is the production of glass beads using 9 parts high
      purity synthetic enstatite (MgSiO3) as the glass former with 1 part of sample
      (sample mass ~1.5 mg). The beads are rapidly prepared (~10 min overall time) by
      fusing the blended mixture on an iridium strip resistance heater in an argon
      purged chamber. Many elements can be measured in the glass bead, but the rare
      earth group in particular is a valuable series in nuclear forensic studies and is
      well-determined using LA-ICP-MS. The REE data obtained from the GRMs, presented
      as chondrite normalized patterns, are in very good agreement with consensus
      patterns. The UOCs have comparable patterns to solution ICP-MS methods and
      published data. The attractions of the current development are its conservation
      of sample, speed of preparation, and suitability for microbeam analysis, all of
      which are favorable for nuclear forensics practitioners and geochemists requiring
      REE patterns from scarce or valuable samples.

PMID- 28446020
TI  - Direct Writing of Microfluidic Footpaths by Pyro-EHD Printing.
AB  - In this study, we report a direct writing method for the fabrication of
      microfluidic footpaths by pyro-electrohydrodynamic (EHD) jet printing. Here, we
      propose the use of a nozzle-free three-dimensional printing technique for the
      fabrication of printed structures that can be embedded in a variety of soft,
      transparent, flexible, and biocompatible polymers and thus easily integrated into
      lab-on-chip devices. We prove the advantage of the high resolution and
      flexibility of pyro-EHD printing for the realization of microfluidic channels
      well below the standard limit in dimension of conventional ink-jet printing
      technique and simply adaptable to the end-user desires in terms of geometry and
      materials. Starting from the description of the innovative approach proposed for
      the channel fabrication, we demonstrate the design, fabrication, and proof of a
      microfluidic matrix of interconnected channels. The method described here could
      be a breakthrough technology for the fabrication of in situ implantable,
      stretchable, and biocompatible devices, opening new routes in the field of
      biomedical engineering and wearable electronics.

PMID- 28446021
TI  - Evaporation of Drops Containing Silica Nanoparticles of Varying Hydrophobicities:
      Exploiting Particle-Particle Interactions for Additive-Free Tunable Deposit
      Morphology.
AB  - We describe the systematic and quantitative investigation of a large number of
      patterns that emerge after the evaporation of aqueous drops containing fumed
      silica nanoparticles (NPs) of varying wettabilities for an extended particle
      concentration range. We show that for a chosen system, the dry pattern morphology
      is mainly determined by particle-particle interactions (Coulomb repulsion and
      hydrophobic attraction) in the bulk. These depend on both particle hydrophobicity
      and particle concentration within the drop. For high and intermediate particle
      concentrations, interparticle hydrophobic attraction is the dominant factor
      defining the deposit morphology. With increasing particle hydrophobicity,
      patterns ranging from rings to domes are observed, arising from the time needed
      for the drop to gel compared with the total evaporation time. On the contrary,
      drops of dilute suspensions maintain a finite viscosity during most of the drop
      lifetime, resulting in dry patterns that are predominantly rings for all particle
      hydrophobicities. In all investigated systems, the NP concentration corresponded
      to a large excess of NPs in the bulk compared with the maximal amount that could
      be adsorbed at available interfaces, making particle-interface interactions such
      as adsorption of hydrophobic NPs at the air-water interface a negligible
      contribution over bulk particle-particle interactions. This work emphasizes the
      advantage of particle surface chemistry in tuning both particle-particle
      interactions and particle deposition onto solid substrates in a robust manner,
      without the need for any additive such as a surfactant.

PMID- 28446022
TI  - Survey of Anthocyanin Composition and Concentration in Diverse Maize Germplasms.
AB  - Increasing consumer demand for natural ingredients in foods and beverages
      justifies investigations into more economic sources of natural colorants. In this
      study, 398 genetically diverse pigmented accessions of maize were analyzed using
      HPLC to characterize the diversity of anthocyanin composition and concentration
      in maize germplasm. One hundred and sixty-seven accessions were identified that
      could produce anthocyanins in the kernel pericarp or aleurone and were classified
      into compositional categories. Anthocyanin content was highest in pericarp
      pigmented accessions with flavanol-anthocyanin condensed forms, similar to the
      Andean Maiz Morado landraces. A selected subset of accessions exhibited high
      broad-sense heritability estimates for anthocyanin production, indicating this
      trait can be manipulated through breeding. This study represents the most
      comprehensive screening of pigmented maize lines to date and will provide
      information to plant breeders looking to develop anthocyanin-rich maize hybrids
      as an economic source of natural colorants in foods and beverages.

PMID- 28446023
TI  - Removing biofilms from stainless steel without changing surface properties
      relevant for bacterial attachment.
AB  - The influence of oxygen (and argon) plasma cleaning and a base-acid cleaning
      procedure on stainless steel surfaces was studied. The main aim was to clean
      stainless steel samples from Paracoccus seriniphilus biofilms without changing
      the surface properties which are relevant for bacterial attachment to allow reuse
      in a biofilm reactor. It is shown that oxygen plasma cleaning, which very
      successfully removes the same kind of biofilm from titanium surfaces, is not
      suitable for stainless steel. It largely influences the surface chemistry by
      producing thick metal oxide layers of varying compositions and changing
      phenomenological surface properties such as wettability. A promising method
      without changing surface properties while cleaning satisfactorily is a
      combination of base and acid reagents at elevated temperature.

PMID- 28446024
TI  - Enhanced Vector Design for Cancer Gene Therapy with Hierarchical Enhancement of
      Therapeutic Transgene Expression.
AB  - A set of vectors for Cre recombinase-dependent expression of the hybrid suicidal
      FCU1 transgene was constructed, including a two-plasmid system wherein the FCU1
      and Cre transgenes reside in separate vectors, and single-plasmid variants in
      which a single plasmid bears both transgenes. To improve the safety profile and
      specificity in cancer gene therapy applications, as well as to ensure stable
      propagation of plasmids in bacterial cells, the Cre/LoxP system components were
      optimized. A bicistronic vector with the Cre expression cassette placed between
      the LoxP sites unidirectionally with FCU1 cDNA resulted in higher therapeutic
      efficiency compared with the double-plasmid system in an enzyme-prodrug suicide
      cancer gene therapy scheme. Therefore, the feasibility of a single-plasmid
      approach in the development of cancer gene therapy with hierarchical enhancement
      of therapeutic transgene expression has been demonstrated.

PMID- 28446025
TI  - Medicinal plant phytochemicals and their inhibitory activities against pancreatic
      lipase: molecular docking combined with molecular dynamics simulation approach.
AB  - Obesity is the worst health risk worldwide, which is linked to a number of
      diseases. Pancreatic lipase is considered as an affective cause of obesity and
      can be a major target for controlling the obesity. The present study was designed
      to find out best phytochemicals against pancreatic lipase through molecular
      docking combined with molecular dynamics (MD) simulation. For this purpose, a
      total of 3770 phytochemicals were docked against pancreatic lipase and ranked
      them on the basis of binding affinity. Finally, 10 molecules (Kushenol K,
      Rosmarinic acid, Reserpic acid, Munjistin, Leachianone G, Cephamycin C,
      Arctigenin, 3-O-acetylpadmatin, Geniposide and Obtusin) were selected that showed
      strong bonding with the pancreatic lipase. MD simulations were performed on top
      five compounds using AMBER16. The simulated complexes revealed stability and
      ligands remained inside the binding pocket. This study concluded that these
      finalised molecules can be used as drug candidate to control obesity.

PMID- 28446026
TI  - Medical Therapy Before Carotid Endarterectomy: Changes Over a 13-Year Period and
      Comparison Between Asymptomatic and Symptomatic Patients.
AB  - We evaluated the evolution of chronic medical therapy in patients admitted for
      carotid endarterectomy (CEA) over a 13-year period and to analyze the difference
      in medical treatment between symptomatic and asymptomatic patients. A
      retrospective study was conducted on patients treated between 2002 and 2015. The
      use of antiplatelets (acetylsalicylic acid [ASA], ticlopidine, and clopidogrel),
      oral anticoagulant therapy (OAT), statins and antihypertensives (angiotensin
      converting enzyme inhibitors [ACE-I]/angiotensin receptor blockers [ARBs], beta
      blockers [BB]) administration was evaluated. During the study period, 852 CEAs
      were performed in 681 (79.9%) asymptomatic patients. Prescription rate increased
      significantly for ASA (+29.2%), clopidogrel (+10.3%), statins (+60.8%), ACE
      I/ARBs (+31.1%), and BB (+19.3%; all Ptrend < .05). No significant modification
      was observed for ticlopidine and OAT (ticlopidine use was abandoned in the recent
      years, but this difference was not significant due to the small numbers). A lower
      medication intake was recorded for symptomatic patients when compared with
      asymptomatic patients, except for OAT and clopidogrel. Our analysis suggests that
      medical therapy has changed over the years for patients with carotid stenosis.
      Although this is a big step toward best medical therapy, preoperative drug
      therapy remains suboptimal in symptomatic patients.

PMID- 28446027
TI  - The Prevalence of Complementary and Alternative Medicine Use Among Dermatology
      Outpatients in Shiraz, Iran.
AB  - The objective of this study was to assess complementary and alternative medicine
      use and its related factors among Iranian dermatology outpatients. In this cross
      sectional study, a self-structured questionnaire was administered to 600
      dermatology outpatients. Mann-Whitney U test, chi-square test, and binary
      logistic regression test were used. A total of 188 (31.3%) patients had used one
      of complementary and alternative medicine methods. The most frequent method used
      was herbal medicine (89.9%). The mean years of duration of the skin condition
      were significantly higher in complementary and alternative medicine users
      compared with nonusers ( P = .037). Patients with acne and alopecia significantly
      used more complementary and alternative medicine (odds ratio: 2.48 and 3.19,
      respectively). There was a significant relationship between education and using
      complementary and alternative medicine ( P < .001). Complementary and alternative
      medicine use is prevalent among our patients and we should think of ways of
      educating general population about complementary and alternative medicine methods
      and their potential risks and benefits and encourage our health care workers to
      communicate these materials with their patients.

PMID- 28446029
TI  - Sugar-free pregnane-type steroids from the roots of Cynanchum stauntonii.
AB  - Two new sugar-free 14,15-secopregnane-type steroids, 14-O-methyl-3-epi
      hirundigenin (1) and 2-deoxyamplexicogenin A (2), along with two known sugar-free
      pregnane-type steroids, were isolated from the 95% ethanol extract of the roots
      of Cynanchum stauntonii. The structures of the new compounds were characterized
      on the basis of extensive spectroscopic analyses, mainly 1D and 2D NMR methods,
      albeit the MS experiments did not display the molecular ion peaks. Compound 2 was
      the aglycones of stauntosides J and K, etc., previously isolated from C.
      stauntonii. The isolation and identification of the new compounds graced the
      structural diversity of pregnane-type steroids from C. stauntonii.

PMID- 28446028
TI  - Impact of Nutritional Supplementation and a Psychomotor Program on Patients With
      Alzheimer's Disease.
AB  - This study aims to evaluate the impact of oral nutritional supplementation (ONS)
      and a psychomotor rehabilitation program on nutritional and functional status of
      community-dwelling patients with Alzheimer's disease (AD). A 21-day prospective
      randomized controlled trial was conducted and third intervention group performed
      a psychomotor rehabilitation program. Patients were followed up for 180 days.
      Mean (standard deviation) score of Mini Nutritional Assessment (MNA) increased
      both in the nutritional supplementation group (NSG; n = 25), 0.4 (0.8), and in
      the nutritional supplementation psychomotor rehabilitation program group (NSPRG;
      n = 11), 1.5 (1.0), versus -0.1 (1.1) in the control group (CG; n = 43), P < .05.
      Further improvements at 90-day follow-up for MNA in NSG: 1.3 (1.2) and NSPRG: 1.6
      (1.0) versus 0.3 (1.7) in CG ( P < .05) were observed. General linear model
      analysis showed that the NSG and NSPRG ?MNA score improved after intervention, at
      21 days and 90 days, was independent of the MNA and Mini-Mental State Examination
      scores at baseline ( Ps > .05). The ONS and a psychomotor rehabilitation program
      have a positive impact on long-term nutritional and functional status of patients
      with AD.

PMID- 28446030
TI  - Anthropometric measures are not accurate predictors of fat mass in ALS.
AB  - BACKGROUND: Anthropometric measurements including body mass index (BMI) and body
      adiposity index (BAI) are widely employed as indicators of fat mass (FM).
      Metabolic abnormalities in amyotrophic lateral sclerosis (ALS) impact disease
      progression, therefore assessment of FM informs care. The aim of this study was
      to determine whether BMI and BAI are accurate predictors of FM in ALS.
      Methodology and main findings: BMI, BAI and percentage FM (determined by air
      displacement plethysmography; FM-ADP) were measured in control (n = 35) and ALS
      (n = 44) participants. While BMI and BAI correlated significantly with FM-ADP,
      neither index provided an accurate estimate of FM. In longitudinally assessed ALS
      participants (n = 29; ~six-month repeat assessment interval), although a change
      in BMI (r2 = 0.62 r = 0.79 p < 0.01) and BAI (r2 = 0.20 r = 0.44, p = 0.02)
      correlated with a change in FM-ADP, the anthropometric measures did not
      consistently reflect increases or decreases observed in FM-ADP.
      CONCLUSIONS/SIGNIFICANCE: Using FM-ADP as the standard, this study suggests that
      BMI and BAI are not accurate measures of FM in ALS. Furthermore, longitudinal
      assessments indicate that changes in BMI and BAI do not consistently reflect true
      changes of FM in ALS.

PMID- 28446031
TI  - Influences of geometrical and mechanical properties of bone tissues in mandible
      behaviour - experimental and numerical predictions.
AB  - The properties and geometry of bone in the mandible play a key role in mandible
      behaviour during a person's lifetime, and attention needs to be paid to the
      influence of bone properties. We analysed the effect of bone geometry, size and
      bone properties in mandible behaviour, experimenting on cadaveric mandibles and
      FE models. The study was developed using the geometry of a cadaveric mandible
      without teeth. Three models of cadaveric condyles were experimentally tested with
      instrumented with four rosettes, and a condyle reaction of 300 N. Four finite
      element models were considered to validate the experiments and analyse mandible
      behaviour. One numeric model was simulated with 10 muscles in a quasi-static
      condition. The experimental results present different condyle stiffness's, of
      448, 215 and 254 N/mm. The values presented in the rosettes are influenced by
      bone geometry and bone thickness; maximum value was -600 MUepsilon in rosette #4,
      and the maximum strain difference between mandibles was 111%. The numerical
      results show that bone density decreases and strain distribution increases in the
      thinner mandible regions. Nevertheless, the global behaviour of the structure
      remains similar, but presents different strain magnitudes. The study shows the
      need to take into account bone characteristics and their evolutions in order to
      improve implant design and fixation throughout the patient life. The change in
      bone stiffness promotes a change in maximum strain distribution with same global
      behaviour.

PMID- 28446033
TI  - Controls over spatial and seasonal variations on isotopic composition of the
      precipitation along the central and eastern portion of Brazil.
AB  - Based on Global Network Isotopes in Precipitation (GNIP) isotopic data set, a
      review of the spatial and temporal variability of delta18O and delta2H in
      precipitation was conducted throughout central and eastern Brazil, indicating
      that dynamic interactions between Intertropical and South Atlantic Convergence
      Zones, Amazon rainforest, and Atlantic Ocean determine the variations on the
      isotopic composition of precipitation over this area. Despite the seasonality and
      latitude effects observed, a fair correlation with precipitation amount was
      found. In addition, Hybrid Single-Particle Lagrangian Integrated Trajectory
      (HYSPLIT) air mass back trajectories were used to quantify the factors
      controlling daily variability in stable isotopes in precipitation. Through a
      linear multiple regression analysis, it was observed that temporal variations
      were consistent with the meteorological parameters derived from HYSPLIT,
      particularly precipitation amount along the trajectory and mix depth, but are not
      dependent on vapour residence time in the atmosphere. These findings also
      indicate the importance of convective systems to control the isotopic composition
      of precipitation in tropical and subtropical regions.

PMID- 28446032
TI  - Effect of Intravesical Liposome-Based Nerve Growth Factor Antisense Therapy on
      Bladder Overactivity and Nociception in a Rat Model of Cystitis Induced by
      Hydrogen Peroxide.
AB  - The aim of this study was to evaluate whether liposome-based local suppression of
      nerve growth factor (NGF) in the bladder has effects on bladder hypersensitivity
      in a rat cystitis model induced by intravesical instillation of hydrogen peroxide
      (HP). HP (1.5%) was intravesically administered to adult female Sprague-Dawley
      rats. Liposomes complexed with NGF antisense oligonucleotide (OND) labeled with
      TYE563 fluorescent tag were intravesically instilled on day 2. Red fluorescence
      from the TYE 563 tag was observed with fluorescent microscopy on day 3. Four
      separate groups of rats were used in the following experiments: (a) sham-liposome
      group, (b) sham-OND group, (c) cystitis-liposome group, and (d) cystitis-OND
      group. Saline or 1.5% HP was intravesically administered on day 0. Empty
      liposomes or liposomes-antisense OND were instilled into the bladder on day 2.
      The following experiments were conducted to evaluate the effect of NGF antisense
      treatment on day 7: (a) continuous cystometry was performed in an awake
      condition; (b) pain behavior induced by instillation of resiniferatoxin into the
      bladder, including licking behavior (lower abdominal licking) and freezing
      behavior (motionless head-turning toward lower abdomen), was observed; (c)
      immunohistochemical staining of the bladder and L6 DRG for NGF was performed; (d)
      the expression of several genes in the bladder was analyzed by reverse
      transcription polymerase chain reaction (RT-PCR); and (e) after Fast Blue was
      injected into the bladder wall, Fast Blue-positive or -negative cells in DRG
      neurons were separately collected by using a laser-capture microdissection method
      7 days later. RT-PCR was performed to evaluate gene expressions in captured
      neuronal cells. The expression of TYE563 was identified only in the urothelial
      layer. In cystometric investigation, intercontraction intervals (ICI) were
      significantly (p = 0.001) shorter in the cystitis-liposome group in comparison to
      the sham-liposome group. ICI was significantly (p = 0.007) longer in the cystitis
      OND group compared to the cystitis-liposome group. Comparisons of the sham
      liposome and the sham-OND groups showed no significant difference in ICI (p =
      0.56). Licking events did not significantly differ among the four groups. In
      contrast, the cystitis-liposome group showed significantly more freezing events
      than the sham-liposome group did (p = 0.002). A significant reduction in the
      number of freezing events was observed in the cystitis-OND group compared to the
      cystitis-liposome group (p = 0.04). Immunofluorescence staining demonstrated that
      NGF expression in the mucosa (p = 0.02) and L6 DRG (p = 0.01) was significantly
      higher in the cystitis-liposome group than it was in the sham-liposome group. The
      expression of NGF was significantly lower in the mucosa (p = 0.002) and L6 DRG (p
      = 0.01) in the cystitis-OND group compared to the cystitis-liposome group. RT-PCR
      showed that the expression of NGF and TRPV1 mRNA in the mucosa was significantly
      higher in the cystitis-liposome group than it was in the sham-liposome group (p =
      0.001 and 0.03, respectively). On the other hand, these gene expressions were
      significantly lower in the cystitis-OND group than they were in the cystitis
      liposome group (p = 0.007 and 0.02, respectively). The cystitis-liposome group
      showed significantly higher expression of TRPA1, P2X3, and BDNF mRNA in labeled
      bladder afferent neurons than the sham-liposome group did (p = 0.03, 0.01, and
      0.001, respectively). These gene expressions were significantly lower in the
      cystitis-OND group compared to the cystitis-liposome group (p = 0.04, 0.006, and
      0.03, respectively). The study indicated that intravesical application of
      liposome-NGF antisense OND significantly improved bladder hypersensitivity
      induced by chemical cystitis in rats. Intravesical treatment with liposome-OND
      conjugates could be a novel local therapy of hypersensitive bladder disorders
      such as bladder pain syndrome/interstitial cystitis.

PMID- 28446034
TI  - Free radicals impair the anti-oxidative stress activity of DJ-1 through the
      formation of SDS-resistant dimer.
AB  - DJ-1 is a causative gene for familial Parkinson's disease (PD). Loss-of-function
      of DJ-1 protein is suggested to contribute to the onset of PD, but the causes of
      DJ-1 dysfunction remain insufficiently elucidated. In this study, we found that
      the SDS-resistant irreversible dimer of DJ-1 protein was formed in human
      dopaminergic neuroblastoma SH-SY5Y cells when the cells were exposed to massive
      superoxide inducers such as paraquat and diquat. The dimer was also formed in
      vitro by superoxide in PQ redox cycling system and hydroxyl radical produced in
      Fenton reaction. We, thus, found a novel phenomenon that free radicals directly
      affect DJ-1 to form SDS-resistant dimers. Moreover, the formation of the SDS
      resistant dimer impaired anti-oxidative stress activity of DJ-1 both in cell
      viability assay and H2O2-elimination assay in vitro. Similar SDS-resistant dimers
      were steadily formed with several mutants of DJ-1 found in familial PD patients.
      These findings suggest that DJ-1 is impaired due to the formation of SDS
      resistant dimer when the protein is directly attacked by free radicals yielded by
      external and internal stresses and that the DJ-1 impairment is one of the causes
      of sporadic PD.

PMID- 28446035
TI  - Falls Suffered by Elderly People From the Perspective of Health Care Personnel: A
      Qualitative Study.
AB  - An exploratory interpretative study was carried out to recognize the factors
      regarded by health care professionals as potential obstacles to the evaluation,
      prevention, and documentation of falls in persons above 65 years of age. Focus
      groups and questionnaires were carried out. Audio recordings were made, and these
      were subsequently transcribed and analyzed in accordance with the Bardin's
      thematic content analysis. Four focus groups of four persons were set up, and 16
      questionnaires were returned. Four thematic categories were obtained. The
      analysis showed a lack of data in records of falls, perhaps for reasons of
      overwork, lack of motivation, awareness, or consistency in the registration
      systems in use. Health care professionals document two types of fall, depending
      on the elderly person's ability to carry out everyday tasks. There is not a
      rigorous and systematic approach for recording falls. Perspectives from health
      care professionals could help in analyzing the causes of falls and suggesting
      comprehensive preventive measures.

PMID- 28446036
TI  - Fusaripeptide A: new antifungal and anti-malarial cyclodepsipeptide from the
      endophytic fungus Fusarium sp.
AB  - From the culture of the endophytic fungus Fusarium sp. isolated from the roots of
      Mentha longifolia L. (Labiatae) growing in Saudi Arabia, a new cyclodepsipeptide,
      namely fusaripeptide A (1), along with three known compounds adenosine (2), 2[(2
      hydroxypropionyl)amino]benzamide (3), and cyclopentanol (4), have been isolated.
      Their structures were determined, using extensive 1D and 2D NMR and HRESI and GC
      mass spectral data. That is the first report for the isolation of compound 4 from
      natural source. In addition, compounds 2 and 3 are reported here for the first
      time from Fusarium sp. The absolute configuration of the amino acid residues of 1
      was assigned by chiral GCMS and Marfey's analysis after acid hydrolysis.
      Fusaripeptide A differs from the reported ones from Fusarium sp. in the length of
      fatty acidic alkyl chain. Compound 1 was evaluated for its antifungal, anti
      malarial, and cytotoxic activities. It exhibited potent antifungal activity
      toward C. albicans, C. glabrata, C. krusei, and A. fumigates with IC50 values of
      0.11, 0.24, 0.19, and 0.14 MUM, respectively. Furthermore, it had significant
      anti-malarial activity toward P. falciparum (D6 clone) with IC50 value of 0.34
      MUM. However, it showed cytotoxic activity toward the tested cell lines.

PMID- 28446037
TI  - Caffeine, coffee, and appetite control: a review.
AB  - Coffee and caffeine consumption has global popularity. However, evidence for the
      potential of these dietary constituents to influence energy intake, gut
      physiology, and appetite perceptions remains unclear. The purpose of this review
      was to examine the evidence regarding coffee and caffeine's influence on energy
      intake and appetite control. The literature was examined for studies that
      assessed the effects of caffeine and coffee on energy intake, gastric emptying,
      appetite-related hormones, and perceptual measures of appetite. The literature
      review indicated that coffee administered 3-4.5 h before a meal had minimal
      influence on food and macronutrient intake, while caffeine ingested 0.5-4 h
      before a meal may suppress acute energy intake. Evidence regarding the influence
      of caffeine and coffee on gastric emptying, appetite hormones, and appetite
      perceptions was equivocal. The influence of covariates such as genetics of
      caffeine metabolism and bitter taste phenotype remain unknown; longer controlled
      studies are needed.

PMID- 28446038
TI  - Clinical criteria of positional vertical nystagmus in vestibular migraine.
AB  - OBJECTIVES: The goal of this study was to identify key diagnostic criteria for
      positional vertical nystagmus caused by vestibular migraine (VM). MATERIALS AND
      METHODS: The study group included a case series of 13 subjects with VM (10
      females and three males with age 38.6 +/- 8.9 years); they were complaining of
      positional vertigo. They were subjected to thorough audiovestibular examination
      and treated with cinnarizine or topiramate Results: The entire study group
      demonstrated positional vertical nystagmus (eight patients had up-beating
      nystagmus and five patients had down-beating nystagmus). The vertigo and
      nystagmus were elicited in one or more of the following positions: the right &
      left Dix-Hallpike, supine with head center, head right, and head left positions.
      The nystagmus had no latency period. It was persistent, non-fatigable and
      markedly reduced by visual fixation. Prophylactic therapy of VM (topiramate or
      cinnarizine) cured the positional vertigo in 92% of the study group. Neither the
      positional vertigo nor the nystagmus recurred in a 3-6 months follow-up period.
      CONCLUSIONS: VM can induce characteristic form of vertical positional nystagmus
      and vertigo, which would be treated by medications used for controlling the VM.

PMID- 28446039
TI  - Intraductal papillary mucinous neoplasm of the pancreas - epidemiology, risk
      factors, diagnosis, and management.
AB  - Intraductal papillary mucinous neoplasm (IPMN) is one of the most common cystic
      neoplasms of the pancreas. It is a heterogeneous disease and can be divided into
      ductal types and morphological subtypes. The incidence of IPMN is increasing,
      likely due to the widespread use of cross-sectional imaging and a growing elderly
      population. IPMN poses an increasing demand on the health care system. Current
      guidelines provide indications for surgery and recommendations for surveillance,
      but management of IPMN is still challenging in routine clinical practice. In this
      article, we review current knowledge about IPMN and provide future directions for
      improving diagnosis and management.

PMID- 28446040
TI  - Characteristics of socially withdrawn youth in France: A retrospective study.
AB  - BACKGROUND: Poor social interactions have been recognized as a symptom since the
      beginnings of psychiatry. As far as socially withdrawn youth (SWY) are concerned,
      studies were mostly conducted on patients seeking care. Our psychiatric outreach
      team called Psymobile was able to reach SWY patients who were not seeking mental
      health care. AIMS: To identify the clinical and socio-demographic characteristics
      of SWY patients referred to our Psymobile unit. METHOD: We carried out a
      retrospective study on the records of patients aged 18-34 years, who were
      referred to Psymobile for 'withdrawal', between April 2012 and December 2015.
      RESULTS: In total, 66 patients were included in the study. SWY are predominantly
      male (80%) from large families or single-parent ones. About 42% had no prior
      contact with a mental health professional before being referred to Psymobile. The
      mean duration of withdrawal is 29 months. In all, 42% of SWY use cannabis and 73%
      present disorders of the sleep-wake schedule. About 71% maintain relations with
      their families and 73% go out occasionally. They are mostly diagnosed with
      schizophrenia (37%) or mood disorders (23%). CONCLUSION: Over one-third of
      Psymobile patients aged 18-34 years were referred on grounds of social
      withdrawal. Our data may illustrate more accurately the situation of youth social
      withdrawal amid the general population than data from help-seeking patients or
      online questionnaires.

PMID- 28446041
TI  - Supernatural versus medical: Responses to mental illness from undergraduate
      university students in Trinidad.
AB  - : Background/Introduction: Perceptions about the aetiology of mental illness are
      likely to influence help-seeking behaviour. Understanding help-seeking behaviour
      will improve service provision and access. Therefore, this is likely to improve
      treatment outcomes. METHODS: We assessed the perceptions and help-seeking
      behaviours surrounding mental illness in a Trinidadian population of 158 tertiary
      level students (136 female, 22 male; mean age 30) by analysing their responses to
      a questionnaire which asked for responses regarding a case vignette of a 25-year
      old young woman exhibiting symptoms suggestive of schizophrenia. RESULTS: Of the
      respondents, 32.3% attributed the symptoms to supernatural causes. Specifically,
      27.8% to someone doing her bad and 24.1% to evil spirits. In all, 77.2% of
      respondents indicated that mental illness was caused by medical problems and
      63.3% to work stress. A minimum of 9.5% of the students therefore have dual
      perceptions regarding causation (77.2 + 32.3 = 109.5) Those who perceived
      causation to be supernatural said they would seek help from both medical ( p =
      .000) and supernatural ( p = .000) modalities. This also applied significantly to
      those who said the causation was medical, that is, seeking both religious
      intervention ( p = .000) and medical intervention (.000) as the first path in the
      health-seeking pathway. CONCLUSION: Dual help-seeking behaviour seems to be the
      functional result of an integration of religious and medical models of mental
      illness causation even in respondents who clearly identified only one of these as
      the likely cause of the illness behaviour.

PMID- 28446042
TI  - The Use of Fibroblasts for Ameliorating Structural Changes Associated with Skin
      Aging.
AB  - Various causes underlie the structural changes associated with skin aging. To
      treat these problems, surgical or nonsurgical approaches are available. One of
      the nonsurgical approaches-regeneration therapy-has become the focus of research
      and clinical applications. In an earlier clinical study, we injected fibroblasts
      into the nasolabial region and lips to counter the structural changes associated
      with skin aging. Assessments performed 12 months after the first injection showed
      mostly adequate satisfaction scores. However, objective evaluation had not been
      performed. In the present clinical study, we injected autologous gingival
      fibroblasts into the nasolabial region and performed objective evaluation using a
      high-resolution digital camera system 12 months after the first injection.
      Objective evaluation showed significant improvement in moisture and grain.
      Subjective evaluation also demonstrated mostly satisfactory results 12 months
      after the first injection. According to our present results, autologous gingival
      fibroblast injection might be capable of ameliorating the structural changes
      associated with skin aging.

PMID- 28446043
TI  - Crown heights in the permanent teeth of 47,XYY males.
AB  - OBJECTIVE: The results in human sex chromosome aneuploidies had shown that the
      extra Y chromosome increases permanent and deciduous tooth crown sizes in the
      mesiodistal and labiolingual directions. The hypothesis of the study was that the
      additional Y chromosome increases the permanent tooth crown growth in a vertical
      dimension. We also aimed to observe possible sex difference in the permanent
      tooth crown height. MATERIAL AND METHODS: Data on 15 47,XYY males or males with
      an extra Y chromosome, nine male relatives (five brothers and four fathers) and
      45 male and 48 female population controls had been gathered previously for
      Professor Lassi Alvesalo's KVANTTI Research Project. The measurements from
      panoramic radiographs were performed of all the applicable teeth, except the
      third molars on both sides of the jaws with a sliding digital calliper. RESULTS:
      All the mean tooth crown heights in the 47,XYY males were larger than in the male
      population controls and the differences were statistically significant in six
      teeth in the maxilla and 10 teeth in the mandible. Apart from few teeth, the
      crown heights in the 47,XYY males were larger than in their male relatives, but
      the difference between these groups was significant only in one tooth. The
      differences between sexes were statistically significant in eight teeth in the
      maxilla. CONCLUSIONS: Based on previous investigations and this work, it is
      evident that the impact of the extra Y chromosome during tooth crown development
      is holistic, increasing permanent tooth sizes in three dimensions in a balanced
      manner.

PMID- 28446044
TI  - Extracapsular dissection for Warthin tumor in the tail of parotid gland.
AB  - CONCLUSIONS: Extracapsular dissection conferred the advantage of reduced
      operation time and morbidity without any recurrence, and it could be considered
      as the treatment of choice for Warthin tumors in the tail of the parotid gland.
      OBJECTIVE: The purpose of this study is to confirm the appropriate surgical
      procedure for Warthin tumor in the tail of the parotid gland, by comparing the
      results of extracapsular dissection and superficial parotidectomy. MATERIALS AND
      METHODS: The medical records of 72 patients with Warthin tumor in the tail of the
      parotid gland who underwent surgery between January 2006 and December 2016 were
      retrospectively reviewed. RESULTS: In the extracapsular dissection group, a total
      of 44 parotid gland operations were performed in 40 patients. In the superficial
      parotidectomy group, a total of 34 parotid gland operations were performed in 32
      patients. The operation time was significantly shorter in the extracapsular
      dissection group than in the superficial parotidectomy group (p<.001, Table 1).
      One patient in the extracapsular dissection group and five patients in the
      superficial parotidectomy group had postoperative facial nerve palsy. Recurrence
      of Warthin tumor in the tail portion of the parotid gland was identified in one
      patient who underwent superficial parotidectomy.

PMID- 28446045
TI  - Telemonitoring in-home complex chronic patients from primary care in routine
      clinical practice: Impact on healthcare resources use.
AB  - BACKGROUND: Recent evidence indicates that home telemonitoring of chronic
      patients reduces the use of healthcare resources. However, further studies
      exploring this issue are needed in primary care. OBJECTIVES: To assess the impact
      of a primary care-based home telemonitoring intervention for highly unstable
      chronic patients on the use of healthcare resources. METHODS: A one-year follow
      up before and after exploratory study, without control group, was conducted.
      Housebound patients with heart failure or chronic lung disease, with recurrent
      hospital admissions, were included. The intervention consisted of patient's self
      measurements and responses to a health status questionnaire, sent daily from
      smartphones to a web-platform (aided by an alert system) reviewed by healthcare
      professionals. The primary outcome measure was the number of hospital admissions
      occurring 12 months before and after the intervention. Secondary outcomes were
      length of hospital stay and number of emergency department attendances. Primary
      care nurses were mainly in charge of the telemonitoring process and were assisted
      by the general practitioners when required. RESULTS: For the 28 patients who
      completed the follow-up (out of 42 included, 13 patients died and 1 discontinued
      the intervention), a significant reduction in hospitalizations, from 2.6
      admissions/patient in the previous year (standard deviation, SD: 1.6) to 1.1 (SD:
      1.5) during the one-year telemonitoring follow-up (P <0.001), and emergency
      department attendances, from 4.2 (SD: 2.6) to 2.1 (SD: 2.6) (P <0.001) was
      observed. The length of hospital stay was reduced non-significantly from 11.4 to
      7.9 days. CONCLUSION: In this small exploratory study, the primary care-based
      telemonitoring intervention seemed to have a positive impact decreasing the
      number of hospital admissions and emergency department attendances.

PMID- 28446046
TI  - Use of embryo culture supernatant to improve clinical outcomes in assisted
      reproductive technology: a systematic review and meta-analysis.
AB  - We planned a systematic review and meta-analysis of randomized clinical trials
      (RCTs) to examine the best available evidence regarding the intrauterine
      instillation of embryo culture supernatant prior to embryo transfer in ART. The
      outcomes were: (i) live birth; (ii) clinical pregnancy; (iii) multiple pregnancy;
      and (iv) miscarriage rates. Five RCTs were considered eligible and available for
      qualitative synthesis. Due to clinical heterogeneity, results from only two
      trials were combined for the meta-analysis. The live birth rate (risk ratio [RR],
      0.47; 95% confidence interval [CI] 0.22-0.98; one study, 60 participants, low
      quality evidence) was found to be significantly lower with intrauterine
      instillation of embryo culture supernatant compared to no intervention. The
      clinical pregnancy rate was similar between the embryo culture supernatant group
      and the control group (RR 1.02 RR, 95% CI 0.77-1.36; two trials, 156
      participants, I2 = 0%). To conclude, this review did not find any improvement in
      clinical pregnancy rate with the intrauterine instillation of embryo culture
      supernatant prior to embryo transfer compared to no intervention in women
      undergoing ART and we remain uncertain regarding its effect on live birth rate.

PMID- 28446047
TI  - Effect of chronic restraint stress on inhibitory gating in the auditory cortex of
      rats.
AB  - A fundamental adaptive mechanism of auditory function is inhibitory gating (IG),
      which refers to the attenuation of neural responses to repeated sound stimuli. IG
      is drastically impaired in individuals with emotional and cognitive impairments
      (i.e. posttraumatic stress disorder). The objective of this study was to test
      whether chronic stress impairs the IG of the auditory cortex (AC). We used the
      standard two-tone stimulus paradigm and examined the parametric qualities of IG
      in the AC of rats by recording the electrophysiological signals of a single-unit
      and local field potential (LFP) simultaneously. The main results of this study
      were that most of the AC neurons showed a weaker response to the second tone than
      to the first tone, reflecting an IG of the repeated input. A fast negative wave
      of LFP showed consistent IG across the sampled AC sites, whereas a slow positive
      wave of LFP had less IG effect. IG was diminished following chronic restraint
      stress at both, the single-unit and LFP level, due to the increase in response to
      the second tone. This study provided new evidence that chronic stress disrupts
      the physiological function of the AC. Lay Summary The effects of chronic stress
      on IG were investigated by recording both, single-unit spike and LFP activities,
      in the AC of rats. In normal rats, most of the single-unit and N25 LFP activities
      in the AC showed an IG effect. IG was diminished following chronic restraint
      stress at both, the single-unit and LFP level.

PMID- 28446048
TI  - Hepatitis due to Epstein-Barr virus and cytomegalovirus: clinical features and
      outcomes.
AB  - OBJECTIVE: To determine the frequency of cytomegalovirus (CMV) and Epstein-Barr
      virus (EBV) hepatitis among those with acute CMV and EBV infection in a
      population based setting and to compare these two types of hepatitis and analyze
      the outcomes. METHODS: A retrospective search was undertaken on all patients with
      IgM antibodies to CMV and EBV during the period of 2006-2015 in the virological
      database of the University Hospital of Iceland covering the metropolitan area of
      Reykjavik (population 202,255). Patients with available liver tests at the
      University Hospital and/or admitted to this institution were included and
      relevant clinical data obtained from medical records. RESULT: Overall, 190
      patients had acute EBV infection during the study period and 118 patients were
      diagnosed with acute CMV. Overall, 82% of patients with acute EBV infection had
      hepatitis, males 43%, median age 17 years, 15% had jaundice and 26% hospitalized.
      Among those with acute CMV infection, 69% had elevated liver tests, 63% males,
      median age 33 years, 9% had jaundice and also 26% hospitalized. Overall, 17% of
      those with CMV hepatitis were immunosuppressed, 6% were pregnant and 4% developed
      Guillain-Barre syndrome following the infection. CONCLUSION: A high proportion of
      patients with acute CMV and EBV developed hepatitis and jaundice, most of those
      patients have good prognosis. Patients with CMV hepatitis were more often
      immunosuppressed, required hospitalization or were pregnant in comparison with
      patients with EBV hepatitis.

PMID- 28446049
TI  - The relationship between the five minute Apgar score, mode of birth and neonatal
      outcomes.
AB  - OBJECTIVE: To investigate the relationship between the five-minute Apgar score
      categories (low, intermediate, and normal), mode of birth and neonatal outcomes.
      METHODS: This was a retrospective cross sectional study of term singleton
      deliveries at Mater Mothers' Hospital in Brisbane, Australia between January 2007
      and December 2015. The five minute score was subdivided in to three categories -
      low (0-3), intermediate (4-6), and normal (>=7). These were correlated with
      adverse neonatal outcomes and mode of birth. The referent cohort was the normal
      Apgar group. RESULTS: The study cohort consisted of 39,258 births with a recorded
      five minute Apgar score. Of these, 38,705 (98.6%) neonates had a normal (>=7)
      Apgar score, 439 (1.1%) had an intermediate score (4-6) and 114 (0.3%) had a low
      (0-3) score. Neonatal complications including respiratory distress, feeding
      problems, hypothermia, and seizures were all significantly associated with both
      low and intermediate Apgar scores. Emergency operative birth (caesarean and
      instrumental) conveyed a higher risk of low and intermediate scores and poorer
      neonatal outcomes. CONCLUSIONS: Low and intermediate five minute Apgar scores
      were strongly associated with mode of birth and poorer neonatal outcomes.

PMID- 28446050
TI  - Smoking is associated with severity of liver fibrosis but not with histological
      severity in nonalcoholic fatty liver disease. Results from a cross-sectional
      study.
AB  - OBJECTIVES: To assess the influence of smoking on histological disease severity
      and fibrosis in real-world NAFLD patients. MATERIAL AND METHODS: Consecutive
      NAFLD patients were identified with liver biopsies performed between 2008 and
      2015. Characteristics such as smoking status and total number of pack years were
      collected. Biopsies were revised and BRUNT fibrosis and NAFLD activity score
      (NAS) determined. Patients with a high NAS (>=5) were compared to patients with a
      low NAS (<5) and with advanced fibrosis (stage 3-4) to patients with no-early
      fibrosis (stage 0-2). Patients with a history of smoking (current or past smoker)
      were defined ever smokers. RESULTS: Fifty-six patients were included (mean age 49
      +/- 14.3, 68.9% males and 39.3% history of smoking). Ever smokers had a higher
      fibrosis score than never smokers; two (IQR 0-3) versus one (IQR 1-1.5) (p =
      .040). Patients with advanced fibrosis smoked significantly more pack years than
      patients with no-early fibrosis; 10.6 (IQR 0-25.8) versus 0 (IQR 0-7) (p = .011).
      There is a weak to moderate correlation between fibrosis stage and number of pack
      years (Spearman's Rho = 0.341, p = .012). There was no difference in NAS between
      never and ever smokers; 2.8 +/- 1.5 versus 3.3 +/- 1.4 (p = .205). Patients with
      NAS <5 had a median number of pack years of 0 (IQR 0-9) versus a median of 10.3
      pack years (IQR 0-24) in patients with NAS >=5 (p = .127). CONCLUSION: Smoking is
      associated with severity of NAFLD-related liver fibrosis but not with
      histological disease severity. This supports the recommendation to cease smoking
      for NAFLD patients.

PMID- 28446052
TI  - Effective intraperitoneal gene transfection system using nanobubbles and
      ultrasound irradiation.
AB  - In this study, we demonstrate the low toxicity and highly efficient and spatially
      improved transfection of plasmid DNA (pDNA) with liposomal nanobubbles (bubble
      liposomes [BLs]) using ultrasound (US) irradiation in mice. Naked pDNA with BLs
      was intraperitoneally injected, followed by US irradiation. The injection volume,
      the duration of US irradiation, and the dose of BLs were optimized. Both BLs and
      US irradiation were essential to achieve high transgene expression from naked
      pDNA. We observed transgene expression in the entire peritoneal tissues,
      including the peritoneal wall, liver, spleen, stomach and small and large
      intestines. The area of transfection could be controlled with focused US
      irradiation. There were few changes in the morphology of the peritoneum, the
      peritoneal function or serum alanine aminotransferase levels, suggesting the
      safety of BLs with US irradiation. Using a tissue-clearing method, the spatial
      distribution of transgene expression was evaluated. BLs with US irradiation
      delivered pDNA to the submesothelial layer in the peritoneal wall, whereas
      transgene expression was restricted to the surface layer in the liver and
      stomach. Therefore, BLs with US irradiation could be an effective and safe method
      of gene transfection to the peritoneum.

PMID- 28446051
TI  - Sleep deprivation sensitizes human craniofacial muscles.
AB  - It is unknown whether and how sleep deprivation influences craniofacial muscle
      sensitivity in healthy humans. We investigated whether total sleep deprivation
      (TSD) and one night of recovery sleep (RS) can alter mechanical pain sensitivity
      in temporal and masseter muscles. Fifteen healthy volunteers participated in
      three consecutive sessions. Pressure pain thresholds were measured on the
      temporal and masseter muscles. Both temporal and masseter muscles became
      sensitized after 24 h of TSD. RS reversed the muscle sensitization.

PMID- 28446053
TI  - Immunotherapy for the treatment of breast cancer.
AB  - INTRODUCTION: Breast cancer is the most common cancer as well as the first cause
      of death by cancer in women worldwide. Although routine treatment improves the
      outcome of early stage breast cancer patients, there is no effective therapy for
      the disseminated disease. Immunotherapy has emerged as a powerful therapeutic
      strategy for the treatment of many cancers. Although traditionally conceived as a
      non-immunogenic tumor, breast cancer is now considered a potential target for
      immunotherapy. Areas covered: In this review, the authors discuss different
      immunotherapeutic strategies that are currently being tested for the treatment of
      breast cancer: These strategies include: (i) blockade of immunological
      checkpoints, (ii) antitumor vaccines, (iii) regulatory T cell blockade, (iv)
      adoptive T cell transfer therapy, (iv) adoptive immunotherapy with monoclonal
      antibodies, and (v) combination of immunotherapy with chemotherapy. Expert
      opinion: A growing body of evidence indicates that immunotherapeutic strategies
      can benefit a larger cohort of breast cancer patients than hitherto anticipated.
      Since breast tumors entail multiple mechanisms to impair antitumor immunity, the
      immunological characterization of individual tumors and the selection of suitable
      combinations of chemotherapeutic and immunotherapeutic approaches are required to
      achieve significant clinical benefit in these patients.

PMID- 28446054
TI  - Pharmacotherapy of relapsed/refractory chronic lymphocytic leukemia.
AB  - INTRODUCTION: The treatment of relapsed/refractory (RR) CLL has been
      revolutionized by the advent of the new oral inhibitors of B-cell receptor (BCR)
      signaling and the pro-survival protein, B-cell lymphoma 2 (BCL2). Additionally,
      new and more potent monoclonal antibodies against CD20 have replaced/may replace
      rituximab in many settings. Areas covered: Herein, we review the entire
      therapeutic landscape of RR CLL, with particular attention to the new small
      molecule kinase inhibitors and BH3-mimetics. We discuss preclinical data with
      these agents in CLL, cover available efficacy and safety information, and examine
      potential resistance mechanisms and possible rational combinations to circumvent
      them. Expert opinion: The availability of potent and selective inhibitors of BCR
      signaling and of the anti-apoptotic functions of BCL2 has enormously enhanced our
      therapeutic armamentarium, with unprecedented efficacy now observed in patients
      who historically had poor outcomes with chemoimmunotherapy (CIT), e.g., those
      with deletion 17p/11q and/or IGHV-unmutated disease. The next challenge is to
      optimally sequence these agents and develop rational combinations that will
      hopefully lead to deeper and more durable remissions than ever seen before.
      Indeed, long term relapse free survival, already achievable with CIT in patients
      with genetically favorable-risk disease, now appears to be a realistic
      possibility for most patients with CLL.

PMID- 28446055
TI  - Investigational drugs for nasopharyngeal carcinoma.
AB  - INTRODUCTION: Nasopharyngeal carcinoma (NPC) is endemic to Southern China and
      Asia and is etiologically associated with the Epstein Barr virus (EBV). Whole
      exome and genome sequencing (WES, WGS) studies of NPC have reported several
      actionable therapeutic targets, and that the mutational load of NPC maybe
      comparable to that of squamous head and neck cancer. These unique biological
      characteristics have been exploited as potential targets and a wide range of
      investigational drugs are being investigated in clinical trials. Area covered:
      This review focused on the latest clinical development of the most promising
      classes of investigational agents in the treatment of advanced NPC. These include
      inhibitors of tumor angiogenesis, kinase signaling pathways and immunotherapy.
      Expert opinion: Checkpoint inhibitors and EBV-specific T-cell therapy have shown
      promising activity in early phase clinical trials, and are being further
      evaluated in randomized studies. For patients whose tumors express genetic
      alterations that are known to predict response to kinase inhibitors, novel trial
      designs such as an 'Umbrella' study may be considered given the abundance of
      targeted agents that are now available for clinical evaluation. It is envisioned
      that regulatory approval for new drugs for advanced NPC will occur in the near
      future.

PMID- 28446056
TI  - High-technology augmentative communication for adults with post-stroke aphasia: a
      systematic review.
AB  - INTRODUCTION: Augmentative and alternative communication (AAC) systems were
      introduced into clinical practice by therapists to help compensate for persistent
      language deficits in people with aphasia. Although, there is currently a push
      towards an increased focus on compensatory approaches in an attempt to maximize
      communication function for social interaction, available studies including AAC
      systems, especially technologically advanced communication tools and systems,
      known as 'high-technology AAC', show key issues and obstacles for these tools to
      become utilized in mainstream clinical practice. Areas covered: The current
      review synthesizes communication intervention studies that involved the use of
      high-technology communication devices to enhance linguistic communication skills
      for adults with post-stroke aphasia. The review focuses on compensatory
      approaches that emphasized functional communication. It also summarizes
      recommendations for the report of studies evaluating high-technology devices that
      may be potentially relevant for other researchers working with adults with post
      stroke aphasia. Expert commentary: Taken together with positive results in
      heterogeneous studies, high-technology devices represent a compensatory strategy
      to enhance communicative skills in individuals with post-stroke aphasia.
      Improvements in the design of studies and reporting of results may lead to better
      interpretation of the already existing scientific results from aphasia
      management.

PMID- 28446057
TI  - Comparison of Survival Outcomes Following Postsurgical Radioactive Iodine Versus
      External Beam Radiation in Stage IV Differentiated Thyroid Carcinoma.
AB  - BACKGROUND: There is a lack of well-powered data regarding outcomes in stage IV
      differentiated thyroid carcinoma (DTC) treated with postsurgical radiation. The
      objective of this study was to examine survival in patients with stage IV
      papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) who
      received radioactive iodine (RAI), external beam radiation therapy (EBRT), or
      neither following surgery. METHODS: In this retrospective cohort study, data
      collected from the National Cancer Data Base (NCDB) yielded 11,832 patients with
      stage IV DTC who underwent primary surgical treatment between 2002 and 2012.
      Patients were stratified by histology and sub-stage. Fully parametric, multilevel
      survival-time models were used to evaluate survival outcomes in three adjuvant
      treatment groups: RAI, EBRT, or no adjuvant radiation. Hazard ratios (HR) and
      time ratios (TR) were calculated against patients who did not receive radiation.
      All models were adjusted for demographic and clinical factors. RESULTS: The mean
      age of all patients was 61.6 years (SD = 11.6), and 57.5% were female. Patients
      who received EBRT had significantly higher 5- and 10-year hazards of death in
      several PTC sub-stages (10-year HRPTC Stage IV-A = 2.12 [confidence interval (CI)
      1.79-2.52]; HRPTC Stage IV-B = 2.03 [CI 1.33-3.10]). For stage IV-B PTC requiring
      EBRT, lifespan after diagnosis was shortened by a factor of 3 when compared to
      patients who did not receive radiation (TRPTC Stage IV-B = 0.32 [CI 0.16-0.62]).
      In contrast, RAI was significantly associated with improved 5- and 10-year
      survival in both PTC and FTC patients regardless of pathological sub-stage. Large
      reductions in mortality were observed in patients with FTC who were treated with
      RAI (HRFTC Stage IV-C = 0.19 [CI 0.06-0.65]). When patients with stage IV-C FTC
      were treated with RAI, life-span after diagnosis doubled (TRFTC Stage IV-C = 1.98
      [CI 1.31-3.00]). CONCLUSIONS: Through the NCDB, this study sought to describe
      prognosis and survival for adjuvant radiation in stage IV DTC. RAI was associated
      with improved survival for stage IV DTC. Despite treatment benefits conferred by
      adjuvant EBRT, indications to treat with EBRT were associated with poorer
      survival outcomes in patients with advanced-stage DTC, particularly PTC.

PMID- 28446059
TI  - Changes in alcohol use after the onset of spinal cord injury.
AB  - OBJECTIVE: Identify the prevalence of alcohol consumption and binge drinking at
      time of spinal cord injury (SCI) onset, compare these rates to data from the
      general population, and identify changes in alcohol use at an average of 17
      months post-injury. DESIGN: Cross sectional, mailed self-report assessment.
      SETTING: A specialty hospital in the southeastern United States. PARTICIPANTS:
      Five hundred sixty-six inpatients completed the baseline measure. After
      eliminating those under age 18, there were 524 participants at baseline. 410 were
      approached for follow-up, with 201 of those responding. INTERVENTIONS: N/A.
      OUTCOME MEASURES: Self-reported assessments were completed during inpatient
      rehabilitation and at follow-up approximately 17 months later. The two primary
      outcomes were the number of days consuming 5 or more drinks (binge drinking) and
      the number of days consuming any alcoholic beverages within the 30 days prior to
      the assessment. Comparison data were taken from the Behavioral Risk Factor
      Surveillance System. RESULTS: At SCI onset, the prevalence of alcohol use,
      particularly binge drinking, was substantially higher than the general population
      (SCI = 44.9%; general population = 13%). Drinking rates decreased by 17 months
      post-injury. CONCLUSION: Alcohol use and binge drinking are elevated over the
      general population at the time of injury. Drinking patterns reflect a decrease
      following injury but remain slightly elevated, signifying a need for
      interventions to minimize long-term health consequences.

PMID- 28446060
TI  - Patterns of Initial Recurrence in Completely Resected Papillary Thyroid
      Carcinoma.
AB  - BACKGROUND: Despite improvements in the surgical and medical treatment of
      papillary thyroid carcinoma (PTC), subsets of patients suffer from structural
      recurrence after initial treatment. This study evaluated the timing and patterns
      of recurrence in completely resected PTC patients. METHODS: A retrospective
      review of a prospectively maintained thyroid cancer database was performed. The
      timing and patterns of recurrence were reviewed in 2250 patients with PTC >1 cm
      who achieved complete remission after total thyroidectomy and/or radioactive
      iodine treatment. Univariate and multivariate analyses were performed to identify
      factors predictive of recurrence patterns. RESULTS: During 8.1 years of mean
      follow-up, 68 (3.0%) patients developed structural recurrences: 53 lymph node
      recurrences (LNR), 11 local soft tissue recurrences (LR), and four distant
      recurrences (DR). Two patients died of DR. Younger patients had a higher
      proportion of LNR, and older patients had a tendency toward LR/DR. LNR showed a
      peak incidence between one and three years after remission, but LR/DR showed a
      delayed peak incidence between two and four years. The factors that significantly
      increased the risk of LNR were multifocal tumor and lymph node metastasis
      (central/lateral). The factors that increased the risk of LR/DR were old age,
      large tumor size (>2 cm), and lateral lymph node metastasis. In addition, central
      neck dissection significantly reduced subsequent LR/DR. CONCLUSION: Patterns of
      recurrence after complete PTC resection are variable and associated with specific
      clinicopathologic factors. Understanding the timing and patterns of recurrence
      may lead to more effective adjuvant treatment and improved long-term follow-up
      strategies.

PMID- 28446062
TI  - Metabolite-Sensing G Protein-Coupled Receptors-Facilitators of Diet-Related
      Immune Regulation.
AB  - Nutrition and the gut microbiome regulate many systems, including the immune,
      metabolic, and nervous systems. We propose that the host responds to deficiency
      (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to
      optimize responses and survival. A family of G protein-coupled receptors (GPCRs)
      termed the metabolite-sensing GPCRs bind to various metabolites and transmit
      signals that are important for proper immune and metabolic functions. Members of
      this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and
      GPR91. In addition, bile acid receptors such as GPR131 (TGR5) and proton-sensing
      receptors such as GPR65 show similar features. A consistent feature of this
      family of GPCRs is that they provide anti-inflammatory signals; many also
      regulate metabolism and gut homeostasis. These receptors represent one of the
      main mechanisms whereby the gut microbiome affects vertebrate physiology, and
      they also provide a link between the immune and metabolic systems. Insufficient
      signaling through one or more of these metabolite-sensing GPCRs likely
      contributes to human diseases such as asthma, food allergies, type 1 and type 2
      diabetes, hepatic steatosis, cardiovascular disease, and inflammatory bowel
      diseases.

PMID- 28446061
TI  - Signaling by Antibodies: Recent Progress.
AB  - IgG antibodies mediate a diversity of immune functions by coupling of antigen
      specificity through the Fab domain to signal transduction via Fc-Fc receptor
      interactions. Indeed, balanced IgG signaling through type I and type II Fc
      receptors is required for the control of proinflammatory, anti-inflammatory, and
      immunomodulatory processes. In this review, we discuss the mechanisms that govern
      IgG-Fc receptor interactions, highlighting the diversity of Fc receptor-mediated
      effector functions that regulate immunity and inflammation as well as determine
      susceptibility to infection and autoimmunity and responsiveness to antibody-based
      therapeutics and vaccines.

PMID- 28446064
TI  - Variability of energy input into selected subsystems of the human-glove-tool
      system: a theoretical study.
AB  - This article presents an application of the energy method to assess the energy
      input introduced into two subsystems of the human-glove-tool system. To achieve
      this aim, a physical model of the system was developed. This consists of dynamic
      models of the human body and the glove described in Standard No. ISO 10068:2012,
      and a model of a hand-held power tool. The energy input introduced into the
      subsystems, i.e., the human body and the glove, was analysed in the domain of
      energy and involved calculating three component energy inputs of forces. The
      energy model was solved using numerical simulation implemented in the
      MATLAB/simulink environment. This procedure demonstrates that the vibration
      energy was distributed quite differently in the internal structure of the two
      subsystems. The results suggest that the operating frequency of the tool has a
      significant impact on the level of energy inputs transmitted into both
      subsystems.

PMID- 28446063
TI  - Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic
      Capabilities.
AB  - The ability of immune cells to survey tissues and sense pathologic insults and
      deviations makes them a unique platform for interfacing with the body and
      disease. With the rapid advancement of synthetic biology, we can now engineer and
      equip immune cells with new sensors and controllable therapeutic response
      programs to sense and treat diseases that our natural immune system cannot
      normally handle. Here we review the current state of engineered immune cell
      therapeutics and their unique capabilities compared to small molecules and
      biologics. We then discuss how engineered immune cells are being designed to
      combat cancer, focusing on how new synthetic biology tools are providing
      potential ways to overcome the major roadblocks for treatment. Finally, we give a
      long-term vision for the use of synthetic biology to engineer immune cells as a
      general sensor-response platform to precisely detect disease, to remodel disease
      microenvironments, and to treat a potentially wide range of challenging diseases.

PMID- 28446065
TI  - Late-recovery from "permanent" vegetative state in the context of severe
      traumatic brain injury: A case report exploring objective and subjective aspects
      of recovery and rehabilitation.
AB  - This article provides a detailed outline of the recovery of a young male patient
      during his emergence from a vegetative state (VS) 19 months after suffering a
      severe traumatic brain injury. Several similar cases have been documented, but
      these tend not to consider the subjective experience of the patient or family;
      our aim was therefore to provide a detailed account that emphasises our
      neuropsychological exploration of the impact of the injury on this person, and
      looks at the experience of his mother along the timeline from his accident to the
      end of a successful period in rehabilitation. Clinical details are presented
      including standardised and non-standard assessments, neuropsychological
      interventions, as well as reflections from the patient himself. Moreover,
      qualitative data from an interview with his mother is used to illustrate the
      emotional impact on family of such a vacillating diagnostic status and prognosis
      for the future. We conclude that late-emergence from VS is increasingly
      documented and further cases must be published to better understand this
      phenomenon. The present case illustrates the emotional impact this situation can
      have on a patient and his or her family, and gives an important insight into a
      patient's view of his or her life and identity following such an event.

PMID- 28446067
TI  - The chemical disruption of human metabolism.
AB  - BACKGROUND: Recent evidence highlights the reality of unprecedented human
      exposure to toxic chemical agents found throughout our environment - in our food
      and water supply, in the air we breathe, in the products we apply to our skin, in
      the medical and dental materials placed into our bodies, and even within the
      confines of the womb. With biomonitoring confirming the widespread
      bioaccumulation of myriad toxicants among population groups, expanding research
      continues to explore the pathobiological impact of these agents on human
      metabolism. METHODS: This review was prepared by assessing available medical and
      scientific literature from Medline as well as by reviewing several books,
      toxicology journals, government publications, and conference proceedings. The
      format of a traditional integrated review was chosen. RESULTS: Toxicant exposure
      and accrual has been linked to numerous biochemical and pathophysiological
      mechanisms of harm. Some toxicants effect metabolic disruption via multiple
      mechanisms. CONCLUSIONS: As a primary causative determinant of chronic disease,
      toxicant exposures induce metabolic disruption in myriad ways, which consequently
      result in varied clinical manifestations, which are then categorized by health
      providers into innumerable diagnoses. Chemical disruption of human metabolism has
      become an etiological determinant of much illness throughout the lifecycle, from
      neurodevelopmental abnormalities in-utero to dementia in the elderly.

PMID- 28446066
TI  - A Novel Three-Dimensional Culture System for Oligodendrocyte Precursor Cells.
AB  - Oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs).
      Mechanisms of OPC differentiation have been extensively examined with two
      dimensional cell culture systems. However, these cellular events may be more
      accurately represented using a three-dimensional (3D) model. In this study, we
      report the development of a novel 3D OPC culture system using gels composed of a
      mixture of collagen and hyaluronan, wherein cultured rat primary OPCs can
      proliferate and differentiate into oligodendrocytes. Our data show that the gel
      concentration and cell-seeding density are critical factors for the numbers of
      OPCs and oligodendrocytes in our 3D culture system. In addition, Notch signaling,
      which supports cell-to-cell communication, may also be important for OPC function
      in our system because a Notch inhibitor DAPT suppressed OPC proliferation and
      differentiation. Taken together, cultured rat OPCs can grow in collagen
      /hyaluronan-based gels, and our novel 3D OPC culture system may offer a useful
      platform for examining the mechanisms of OPC function in vitro.

PMID- 28446068
TI  - Multiplex PCR detection of Cryptosporidium sp, Giardia lamblia and Entamoeba
      histolytica directly from dried stool samples from Guinea-Bissauan children with
      diarrhoea.
AB  - BACKGROUND: In developing countries, diarrhoea is the most common cause of death
      for children under five years of age, with Giardia lamblia, Cryptosporidium and
      Entamoeba histolytica as the most frequent pathogenic parasites. Traditional
      microscopy for stool parasites has poor sensitivity and specificity, while new
      molecular methods may provide more accurate diagnostics. In poor regions with
      sample storage hampered by uncertain electricity supply, research would benefit
      from a method capable of analysing dried stools. METHODS: A real-time multiplex
      PCR method with internal inhibition control was developed for detecting Giardia
      lamblia, Cryptosporidium hominis/parvum and Entamoeba histolytica directly from
      stool specimens. Applicability to dried samples was checked by comparing with
      fresh ones in a small test material. Finally, the assay was applied to dried
      specimens collected from Guinea-Bissauan children with diarrhoea. RESULTS: The
      PCR's analytical sensitivity limit was 0.1 ng/ml for G. lamblia DNA, 0.01 ng/ml
      for E. histolytica DNA and 0.1 ng/ml for Cryptosporidium sp. In the test
      material, the assay performed similarly with fresh and dried stools. Of the 52
      Guinea-Bissauan samples, local microscopy revealed a parasite in 15%, while PCR
      detected 62% positive for at least one parasite: 44% of the dried samples had
      Giardia, 23% Cryptosporidium and 0% E. histolytica. CONCLUSIONS: Our new
      multiplex real-time PCR for protozoa presents a sensitive method applicable to
      dried samples. As proof of concept, it worked well on stools collected from
      Guinea-Bissauan children with diarrhoea. It provides an epidemiological tool for
      analysing dried specimens from regions poor in resources.

PMID- 28446069
TI  - Handedness and lower face variability: Findings in three national surveys.
AB  - Lower face variability in modern humans has been associated with a series of
      phenotypic characteristics including body architecture and handedness. The aim of
      this study was to provide a systematic review of lower face variability and
      handedness in national health surveys conducted in the United States. Three
      informative surveys with a total of 13,663 participants were identified. Lower
      face variability was described as one of six facial phenotypes and related to
      handedness using logistic regression models while adjusting for sex, ancestry,
      geography, and income. The results on 13,536 participants with complete
      information showed that bilateral retrognathism-a marker for a lower face
      phenotype characterized by a convex facial profile and slender jaws-was
      associated with a 25% increased odds for non-right-handedness (odds ratio, 1.250;
      95% confidence interval: 1.076-1.453, p-value < .004). This association between
      non-right-handedness and a convex facial profile may unexpectedly find its origin
      in the genetic polymorphisms which determine tuberculosis susceptibility.

PMID- 28446072
TI  - The Influence of Force Direction on the Fracture Pattern and Fracture Resistance
      of Canine Teeth in Dogs.
AB  - Biomechanical studies of the elongated canine tooth of animals are few, and thus
      our understanding of mechanical and physical properties of animal teeth is
      limited. The objective of the present study was to evaluate the influence of
      force direction on fracture resistance and fracture pattern of canine teeth in an
      ex vivo dog cadaver model. Forty-five extracted canine teeth from laboratory
      beagle dogs were standardized by hard tissue volume and randomly distributed
      among 3 force direction groups. The teeth were secured within a universal testing
      machine and a load was applied at different directions based on testing group.
      The maximum force to fracture and the fracture pattern classification were
      recorded for each tooth. After correcting for hard tissue cross-sectional area in
      a multivariate analysis, no significant difference in the amount of force
      required for fracture was apparent between the different force direction groups.
      However, the influence of force direction on fracture pattern was significant.
      The results of this study may allow the clinician to educate clients on possible
      causal force directions in clinically fractured teeth and, thus, help prevent any
      contributing behavior in the future.

PMID- 28446073
TI  - Recurrent Hemarthrosis due to Iatrogenic AVF Treated With Onyx Embolization.
AB  - A 78-year-old gentleman presented with recurrent symptomatic hemarthrosis after
      total knee arthroplasty. His workup revealed an iatrogenic arteriovenous fistula
      (iAVF). The iAVF was embolized with the Onyx Liquid Embolization System with
      resolution of his symptoms up to 10 months of follow-up. This is the first
      description to our knowledge of an iatrogenic hemarthrosis after total knee
      arthroplasty successfully treated with Onyx solution embolization.

PMID- 28446071
TI  - Human Neural Stem Cell Therapy for Chronic Ischemic Stroke: Charting Progress
      from Laboratory to Patients.
AB  - Chronic disability after stroke represents a major unmet neurologic need.
      ReNeuron's development of a human neural stem cell (hNSC) therapy for chronic
      disability after stroke is progressing through early clinical studies. A Phase I
      trial has recently been published, showing no safety concerns and some promising
      signs of efficacy. A single-arm Phase II multicenter trial in patients with
      stable upper-limb paresis has recently completed recruitment. The hNSCs
      administrated are from a manufactured, conditionally immortalized hNSC line
      (ReNeuron's CTX0E03 or CTX), generated with c-mycERTAM technology. This
      technology has enabled CTX to be manufactured at large scale under cGMP
      conditions, ensuring sufficient supply to meets the demands of research, clinical
      development, and, eventually, the market. CTX has key pro-angiogenic, pro
      neurogenic, and immunomodulatory characteristics that are mechanistically
      important in functional recovery poststroke. This review covers the progress of
      CTX cell therapy from its laboratory origins to the clinic, concluding with a
      look into the late stage clinical future.

PMID- 28446074
TI  - Open Repair of Hepatic Artery and Celiac Artery Aneurysms in a Patient With Prior
      Aortic Dissection With an Iliac to Hepatic Artery Bypass.
AB  - A 67-year-old male with a history of an aortic dissection was found to have a
      large hepatic and celiac artery aneurysm. Due to the extent of the dissection
      within the aorta, a bypass was performed from his iliac artery to the hepatic
      bifurcation, followed by exclusion and ligation of the aneurysms.

PMID- 28446075
TI  - Comparison of Bronchoscopy-Guided and Real-Time Ultrasound-Guided Percutaneous
      Dilatational Tracheostomy: Safety, Complications, and Effectiveness in Critically
      Ill Patients.
AB  - OBJECTIVE: To compare the efficacy, safety, and incidence of complications
      between fiber-optic bronchoscopy-guided percutaneous dilatational tracheostomy
      (FOB-PDT) and ultrasound-guided percutaneous dilatational tracheostomy (US-PDT)
      and to determine whether US-PDT is a viable alternative to FOB-PDT. METHODS: This
      randomized prospective study was carried out in 80 patients who were randomly
      divided into US-PDT and FOB-PDT groups. Demographic data and Acute Physiology and
      Chronic Health Evaluation II (APACHE II), procedure duration, hemorrhage status,
      complications, procedure difficulty, displacement of entry location after US, and
      hemodynamic data were evaluated in both groups. Tracheal incision was performed
      with real-time US and a transverse probe position in the out-of-plane mode.
      RESULTS: No significant differences were observed between the 2 groups in terms
      of demographic data, oral intubation time, APACHE II values, difficulty of the
      procedure, or the number of needle interventions ( P > .05). The mean hemorrhage
      ratio of the FOB-PDT group was significantly higher than that of the US-PDT group
      ( P < .05). The entry location was changed in 6 patients in the US-PDT group
      following neck examination with US. The mean duration of the procedure for the
      FOB-PDT group was significantly longer than that for the US-PDT group ( P < .05).
      CONCLUSION: Ultrasound-guided percutaneous dilatational tracheostomy is a safe
      procedure for critically ill patients and has the advantages of a low
      complication rate, short duration of procedure, being informative with regard to
      neck anatomy, and facilitating prevention of vascular puncture. Thus, US-PDT can
      be used as an alternative to FOB-PDT.

PMID- 28446076
TI  - Behavior of uncharged oximes compared to HI6 and 2-PAM in the human AChE-tabun
      conjugate: a molecular modeling approach.
AB  - Tabun is one of the most dangerous nerve agents because it has deleterious
      effects like inhibition of the essential enzymes acetylcholinesterase (AChE) and
      butyrylcholinesterase. Some oximes such HI6 as 2-PAM are nucleophiles that are
      capable to reactivate inhibited human AChE under some conditions. Zwitterionic
      and cationic species have the best chance of productive action on inhibited AChE.
      However uncharged oximes can give important interaction information. In order to
      investigate the interaction and behavior of cationic and uncharged oximes, we
      performed molecular docking simulations and molecular dynamics and calculated
      binding energies of complexes of these compounds with human AChE. The uncharged
      oximes of larger structure were more susceptible to the influence of the
      substituents on the phosphorus atom and presented low binding energies. In
      contrast, HI 6 and 2-PAM showed high binding energy values with great
      contribution of the amino acid Asp74, demonstrating the importance of the
      quaternary nitrogen to the affinity and interaction of the oximes/AChE tabun
      inhibited complexes.

PMID- 28446077
TI  - Expression of MMP-13 in human temporomandibular joint disc derangement and
      osteoarthritis.
AB  - OBJECTIVE: MMP-13 performs digestion of collagen, which is a primary component of
      the temporomandibular joint (TMJ) articular disc. This study evaluated the
      expression of MMP-13 in patients with anterior disc displacement with (ADDwR) and
      without reduction (ADDwoR), and in the presence of TMJ osteoarthrosis. METHODS:
      Thirty-nine human temporomandibular joint disc samples were collected and divided
      in two ways: ADDwR (21 samples), ADDwoR (10 samples), and a control group (8
      samples); and with osteoarthrosis (10 samples) and without osteoarthrosis (29
      samples). Immunostaining of the TMJ discs was statistically compared between the
      groups. RESULTS: There was no statistically significant difference for the area
      of MMP-13 immunostaining between the control group, ADDwR, and ADDwoR, nor
      between groups with and without osteoarthrosis. CONCLUSION: This study suggests
      MMP-13 is not significantly involved in collagen degradation in human TMJ disc
      displacement or osteoarthrosis.

PMID- 28446078
TI  - Serial Neck Ultrasonographic Evaluation of Changes in Papillary Thyroid Carcinoma
      During Pregnancy.
AB  - BACKGROUND: Papillary thyroid cancer (PTC) is a common malignancy diagnosed
      during pregnancy. However, there is little information on the behavior of PTC
      during pregnancy. The aim of this study was to evaluate the natural course of PTC
      in pregnant women. METHODS: The study included 19 patients with PTC who delayed
      thyroid surgery because they were diagnosed with PTC just before or during the
      early stages of pregnancy. Serial neck ultrasonography (US) was used to evaluate
      PTCs before surgical treatment and the clinical outcomes after surgery. RESULTS:
      The median maximal PTC size at initial diagnosis on US was 0.91 cm (interquartile
      range [IQR] 0.61-1.11), and 13/19 (68.4%) patients had micro-PTCs (<=1 cm). The
      median maximal PTC size after a median 9.5 months of follow-up was 0.98 cm (IQR
      0.72-1.12). There were three (16%) patients who showed a size increase, and five
      (26%) patients showed a volume increase during the follow-up periods. There was
      no clinically relevant change in the maximal tumor size during the follow-up
      period (p = 0.16). Serial US measurements of PTC size in seven available patients
      in each trimester showed no significant differences between the different
      trimesters (first vs. second trimester p = 0.81; second vs. third trimester p =
      0.99). No newly developed lesions in the thyroid or cervical lymph nodes were
      detected by neck US during the follow-up period. Among 19 patients, 16 underwent
      thyroid surgery after delivery, and the median duration from diagnosis to surgery
      was 11.9 months. CONCLUSIONS: No clinically relevant changes associated with a
      progression of PTC were observed during pregnancy. Delayed thyroid surgery with
      active surveillance can be an appropriate approach for pregnant patients with
      PTC.

PMID- 28446081
TI  - College scheme aids nursing in Zambia.
AB  - For the past six years, the Department for International Development has been
      funding projects between health organisations in the UK and those in resource
      poor settings as part of its Health Partnership Scheme.

PMID- 28446082
TI  - Ask dying adults about their spiritual beliefs.
AB  - Essential facts Religion should be included in the vital discussions about the
      care people and those close to them want to receive in the last two to three days
      of life, according to the National Institute for Health and Care Excellence
      (NICE).

PMID- 28446083
TI  - Domestic abuse.
AB  - A new Department of Health (DH) resource, Responding to Domestic Abuse, has been
      developed to help staff working in healthcare services respond to domestic abuse.

PMID- 28446084
TI  - In rooting out errors, evidence holds the key.
AB  - Healthcare is in crisis in the US, where preventable clinical errors are the
      third leading cause of death. Now is the time to create healthcare cultures where
      best practice is the standard.

PMID- 28446085
TI  - Cancer research.
AB  - Macmillan Cancer Support runs an annual grant-funding scheme for UK-based
      researchers and this year the topics for research proposals are the role of
      primary care in meeting the needs of people living with cancer, people living
      with cancer that cannot be cured, and the use of digital technology to improve
      the experience and outcomes of people living with cancer. Closing date for
      applications is 8 May.

PMID- 28446086
TI  - Whistleblowing.
AB  - The government is consulting on regulations to protect people who have made
      protected disclosures from discrimination by employers when applying for NHS
      posts.

PMID- 28446087
TI  - Transition to adult services.
AB  - Young people with long-term health conditions diagnosed in childhood are
      supported by children's services and usually move to adult health services as
      they get older. However, this process can be stressful and confusing, especially
      if there are problems with communication or gaps in care delivery.

PMID- 28446088
TI  - End of life care.
AB  - Skills for Health, Health Education England and Skills for Care have launched a
      new end of life education and training framework to provide tailored, high
      quality care and support to patients with advanced incurable illness and their
      families.

PMID- 28446089
TI  - Improving leadership skills and health outcomes.
AB  - The Mary Seacole awards provide an opportunity for individuals to be recognised
      for their outstanding work in black and minority ethnic (BME) communities. Set up
      in 2004, the awards are funded by Health Education England and made in
      association with the Royal College of Nursing, Royal College of Midwives, Unison
      and Unite, with the support of NHS Employers. They are open to nurses, midwives
      and health visitors in England, and recipients need not come from a BME
      background.

PMID- 28446093
TI  - Are we doing enough to support new recruits?
AB  - It is often said the skills and expertise of our staff are among our greatest
      resources. So, reading this issue's article by Susan Wilkinson and Richard
      Hayward ( page 30 ) on band 5 nurses' insights into professional development has
      prompted me to ask: 'Are we doing enough to support new recruits to our
      profession?'

PMID- 28446095
TI  - Schwartz Center Rounds can make staff effective.
AB  - A study into the effectiveness of Schwartz Center Rounds on healthcare staff has
      revealed that the programme can increase empathy for patients and improve
      teamwork.

PMID- 28446094
TI  - Staff who work long shifts more likely to call in sick, according to new
      research.
AB  - Nurses who work 12-hour shift patterns are more likely to take sickness leave,
      new research shows.

PMID- 28446096
TI  - Band 5 nurses' perceptions and experiences of professional development.
AB  - Aim The aim of this qualitative study was to explore band 5 nurses' perceptions
      and experiences of professional development in an acute care provider to identify
      what, if any, effect these have on their job satisfaction and intention to stay
      in post. Method An adapted grounded theory approach was used. Theoretical
      sampling identified band 5 nurses in their first 24 months of employment in the
      trust. Data were collected through focus groups and analysed using the constant
      comparative method. Results Findings suggest that the provision of, and support
      for, development opportunities affect nurses' job satisfaction, and investment in
      these opportunities is likely to improve staff retention. Conclusion It is
      important that resources and funding can be used flexibly so nurse leaders can
      ensure nursing staff are provided with the training and career progression they
      require. This will support them to achieve and retain essential competencies, and
      improve job satisfaction and staff retention.

PMID- 28446097
TI  - Evidence of discrimination against BME nurses revealed.
AB  - University of Greenwich researchers responded to an advert from the Nursing and
      Midwifery Council (NMC) offering funding for an investigation into its fitness-to
      practise (FtP) processes amid concerns about the treatment of NHS staff from
      black and minority ethnic (BME) backgrounds.

PMID- 28446098
TI  - World Cafe: a proactive approach to working with mentors.
AB  - Mentors are vital for supporting nursing students' learning in practice, but
      increasing demands on registered nurses can make this a challenging part of their
      role. This article describes how a new education team in Jersey used the World
      Cafe approach to working with mentors on a mentor update day. It explains how the
      cafe environment helped mentors to share ideas, develop opportunities to support
      students' learning in practice areas, increase interdepartmental working and
      increased communication between the education department and mentors.

PMID- 28446099
TI  - Evidence-based practice.
AB  - If you have a long commute to work, you may be interested in filling the time by
      listening to the latest Cochrane evidence through podcasts.

PMID- 28446101
TI  - 'Be courageous and stand up for what you believe is right'.
AB  - What is your job? I am a practice facilitator on an acute colorectal and urology
      ward in Ysbyty Gwynedd Hospital, part of Betsi Cadwaladr University Health Board
      (BCUHB). My main role is to support newly qualified nurses and students.

PMID- 28446102
TI  - How much is enough? Using Delphi to explore the clinical-contact-time and return
      to-practice needs of military nurses.
AB  - Aim Military nurses are required to deploy worldwide at any time to support
      British forces. They must maintain military and clinical skills, and fulfil other
      military commitments as required. These diverse responsibilities make it
      challenging for military nurses to maintain the level of clinical expertise they
      require for short-notice deployments. A service evaluation was conducted to
      investigate issues related to clinical contact time (CCT) and to return to
      practice (RTP) for military nurses. Method A consultative approach was taken in
      the form of a modified Delphi study, followed by a military judgement panel
      (focus group). Results Two aspects of the study are reported here: CCT and RTP.
      Panellists considered that policy rather than guidance is needed to ensure
      military nurses achieve the requisite CCT to prepare them for operational
      deployment. Additionally, there was a broad consensus on a range of issues,
      including minimum CCT for specific groups and mechanisms to support those
      returning to practice. Conclusion Maintaining clinical skills, and the challenges
      of returning to practice, require careful consideration in a mobile workforce
      with wide-ranging commitments. Prescribing CCT, ensuring assignment orders
      specify CCT and the introduction of job plans should help military nurses
      maintain their core and specialist nursing skills, guide commanders and reinforce
      the culture of 'hands-on nursing' as a valid use of time.

PMID- 28446103
TI  - Preceptorships planned for all new nurses and midwives.
AB  - All new nurses should complete a mandatory preceptorship year, an academic
      heading up the regulator's 'radical' overhaul of education standards has said.

PMID- 28446104
TI  - Scotland to enshrine safe staffing in law.
AB  - The Scottish Government has announced it will consult on enshrining in law the
      use of planning tools to set nurse staffing numbers in the NHS.

PMID- 28446105
TI  - Evaluating methods of correcting for multiple comparisons implemented in SPM12 in
      social neuroscience fMRI studies: an example from moral psychology.
AB  - In fMRI research, the goal of correcting for multiple comparisons is to identify
      areas of activity that reflect true effects, and thus would be expected to
      replicate in future studies. Finding an appropriate balance between trying to
      minimize false positives (Type I error) while not being too stringent and
      omitting true effects (Type II error) can be challenging. Furthermore, the
      advantages and disadvantages of these types of errors may differ for different
      areas of study. In many areas of social neuroscience that involve complex
      processes and considerable individual differences, such as the study of moral
      judgment, effects are typically smaller and statistical power weaker, leading to
      the suggestion that less stringent corrections that allow for more sensitivity
      may be beneficial and also result in more false positives. Using moral judgment
      fMRI data, we evaluated four commonly used methods for multiple comparison
      correction implemented in Statistical Parametric Mapping 12 by examining which
      method produced the most precise overlap with results from a meta-analysis of
      relevant studies and with results from nonparametric permutation analyses. We
      found that voxelwise thresholding with familywise error correction based on
      Random Field Theory provides a more precise overlap (i.e., without omitting too
      few regions or encompassing too many additional regions) than either clusterwise
      thresholding, Bonferroni correction, or false discovery rate correction methods.

PMID- 28446106
TI  - Real-time detection of lesion development in acute brain injury.

PMID- 28446109
TI  - Clot retrieval and acute stroke care.

PMID- 28446107
TI  - Euthanasia and physician-assisted suicide: focus on the data.

PMID- 28446110
TI  - Regenerative neurology: meeting the need of patients with disability after
      stroke.

PMID- 28446111
TI  - Undetected and underserved: the untold story of patients who had a minor stroke.

PMID- 28446112
TI  - Strategic lacunar infarction.

PMID- 28446113
TI  - Reducing the burden of neurological disease and mental illness.

PMID- 28446114
TI  - Transforming the management of stroke.

PMID- 28446115
TI  - Assessing the outcome of stroke in Australia.

PMID- 28446116
TI  - Risk-adjusted hospital mortality rates for stroke: evidence from the Australian
      Stroke Clinical Registry (AuSCR).
AB  - OBJECTIVES: Hospital data used to assess regional variability in disease
      management and outcomes, including mortality, lack information on disease
      severity. We describe variance between hospitals in 30-day risk-adjusted
      mortality rates (RAMRs) for stroke, comparing models that include or exclude
      stroke severity as a covariate. DESIGN: Cohort design linking Australian Stroke
      Clinical Registry data with national death registrations. Multivariable models
      using recommended statistical methods for calculating 30-day RAMRs for hospitals,
      adjusted for demographic factors, ability to walk on admission, stroke type, and
      stroke recurrence. SETTING: Australian hospitals providing at least 200 episodes
      of acute stroke care, 2009-2014. MAIN OUTCOME MEASURES: Hospital RAMRs estimated
      by different models. Changes in hospital rank order and funnel plots were used to
      explore variation in hospital-specific 30-day RAMRs; that is, RAMRs more than
      three standard deviations from the mean. RESULTS: In the 28 hospitals reporting
      at least 200 episodes of care, there were 16 218 episodes (15 951 patients;
      median age, 77 years; women, 46%; ischaemic strokes, 79%). RAMRs from models not
      including stroke severity as a variable ranged between 8% and 20%; RAMRs from
      models with the best fit, which included ability to walk and stroke recurrence as
      variables, ranged between 9% and 21%. The rank order of hospitals changed
      according to the covariates included in the models, particularly for those
      hospitals with the highest RAMRs. Funnel plots identified significant deviation
      from the mean overall RAMR for two hospitals, including one with borderline
      excess mortality. CONCLUSIONS: Hospital stroke mortality rates and hospital
      performance ranking may vary widely according to the covariates included in the
      statistical analysis.

PMID- 28446117
TI  - Prevalence of microcephaly in an Australian population-based birth defects
      register, 1980-2015.
AB  - OBJECTIVES: To describe the prevalence and characteristics of microcephaly in a
      geographically defined Australian population. DESIGN, SETTING AND PARTICIPANTS:
      Descriptive epidemiological study of microcephaly cases ascertained by the
      Western Australian Register of Developmental Anomalies, 1980-2015, defining
      microcephaly as an occipito-frontal head circumference below the third percentile
      or more than two standard deviations below the mean sex- and age-appropriate
      distribution curve. MAIN OUTCOME MEASURES: Microcephaly prevalence (per 10 000
      births) was calculated for cases with known and unknown causes, and by
      demographic characteristics. Temporal trends were analysed, and prevalence ratios
      (PRs) and 95% CIs calculated for Aboriginal and non-Aboriginal births. RESULTS:
      For births during 1980-2009 (ie, with at least 6 years' follow-up and therefore
      complete case ascertainment), 416 cases were identified, a prevalence of 5.5 per
      10 000 births (95% CI, 4.95-6.02), or 1 in 1830 births. There was no significant
      temporal trend in prevalence (P = 0.23). Most cases were in live-born children
      (389, 93.5%), and other major birth defects were diagnosed in 335 of the affected
      children (80%). Prevalence was higher in Aboriginal births (PR, 4.5; 95% CI, 3.55
      5.73). A cause of microcephaly was identified in 186 cases (45% of cases), and
      more often for Aboriginal (64 cases, 70%) than non-Aboriginal births (122 cases,
      38%). The most frequent known cause of microcephaly in Aboriginal births was
      fetal alcohol spectrum disorder (FASD; 11 per 10 000 births); monogenic (0.68 per
      10 000) and chromosomal conditions (0.59 per 10 000 births) were the most common
      causes in non-Aboriginal births. CONCLUSIONS: These data provide a baseline for
      prospective surveillance of microcephaly. We identified a high proportion of
      cases without known cause, highlighting the need for clinicians to carefully
      investigate all possibilities, including emerging infections. FASD is an
      important cause of microcephaly in the Aboriginal population.

PMID- 28446118
TI  - Motor neurone disease: progress and challenges.
AB  - Major progress has been made over the past decade in the understanding of motor
      neurone disease (MND), changing the landscape of this complex disease. Through
      identifying positive prognostic factors, new evidence-based standards of care
      have been established that improve patient survival, reduce burden of disease for
      patients and their carers, and enhance quality of life. These factors include
      early management of respiratory dysfunction with non-invasive ventilation,
      maintenance of weight and nutritional status, as well as instigation of a
      multidisciplinary team including neurologists, general practitioners and allied
      health professionals. Advances in technology have enhanced our understanding of
      the genetic architecture of MND considerably, with implications for patients,
      their families and clinicians. Recognition of extra-motor involvement,
      particularly cognitive dysfunction, has identified a spectrum of disease from MND
      through to frontotemporal dementia. Although riluzole remains the only disease
      modifying medication available in clinical practice in Australia, several new
      therapies are undergoing clinical trials nationally and globally, representing a
      shift in treatment paradigms. Successful translation of this clinical research
      through growth in community funding, awareness and national MND research
      organisations has laid the foundation for closing the research-practice gap on
      this debilitating disease. In this review, we highlight these recent
      developments, which have transformed treatment, augmented novel therapeutic
      platforms, and established a nexus between research and the MND community. This
      era of change is of significant relevance to both specialists and general
      practitioners who remain integral to the care of patients with MND.

PMID- 28446119
TI  - Neurobionics and the brain-computer interface: current applications and future
      horizons.
AB  - The brain-computer interface (BCI) is an exciting advance in neuroscience and
      engineering. In a motor BCI, electrical recordings from the motor cortex of
      paralysed humans are decoded by a computer and used to drive robotic arms or to
      restore movement in a paralysed hand by stimulating the muscles in the forearm.
      Simultaneously integrating a BCI with the sensory cortex will further enhance
      dexterity and fine control. BCIs are also being developed to: provide ambulation
      for paraplegic patients through controlling robotic exoskeletons; restore vision
      in people with acquired blindness; detect and control epileptic seizures; and
      improve control of movement disorders and memory enhancement. High-fidelity
      connectivity with small groups of neurons requires microelectrode placement in
      the cerebral cortex. Electrodes placed on the cortical surface are less invasive
      but produce inferior fidelity. Scalp surface recording using
      electroencephalography is much less precise. BCI technology is still in an early
      phase of development and awaits further technical improvements and larger
      multicentre clinical trials before wider clinical application and impact on the
      care of people with disabilities. There are also many ethical challenges to
      explore as this technology evolves.

PMID- 28446120
TI  - Voluntary euthanasia laws in Australia: are we really better off dead?

PMID- 28446121
TI  - Voluntary euthanasia laws in Australia: are we really better off dead?

PMID- 28446122
TI  - Pre-hospital thrombolysis in ST-segment elevation myocardial infarction: a
      regional Australian experience.

PMID- 28446123
TI  - Pre-hospital thrombolysis in ST-segment elevation myocardial infarction: a
      regional Australian experience.

PMID- 28446124
TI  - The stroke gap.

PMID- 28446125
TI  - Soluble transferrin receptor as a marker of erythropoiesis in patients undergoing
      high-flux hemodialysis.
AB  - Anemia is a common complication in chronic kidney disease (CKD) patients
      receiving hemodialysis. The effect of high-flux dialysis (HFD) on anemia remains
      unclear. This prospective study aimed to evaluate the effect of HFD on anemia,
      and the potential of soluble transferrin receptor (sTfR) as a marker of iron
      status and erythropoiesis in CKD patients on hemodialysis. Forty patients, who
      switched from conventional low-flux dialysis to HFD for 12 months, were enrolled
      in this study. The levels of sTfR, hemoglobin (Hb), iron, and nutritional
      markers, as well as the dose of recombinant human erythropoietin (rhEPO) and use
      of chalybeate were determined at 0, 2, 6, and 12 months after starting HFD. HFD
      significantly increased the hemoglobin level and reduced sTfR level in CKD
      patients (p < 0.05). In addition, significant decreasing linear trends were
      observed for rhEPO dosage and chalybeate use (p < 0.05). The level of sTfR was
      positively correlated with the percentage of reticulocytes (RET%), rhEPO dose,
      and chalybeate use, while it was negatively correlated with Hb levels and total
      iron-binding capacity results (all p < 0.05). A univariate generalized estimating
      equation (GEE) model showed that the Hb level, RET%, rhEPO dose, and chalybeate
      use were the variables associated with sTfR levels. A multivariate GEE model
      showed that the time points when hemodialysis was performed were the variables
      associated significantly with sTfR levels. Overall, our findings suggest that HFD
      can effectively improve renal anemia in hemodialysis patients, and sTfR could be
      used as a marker of erythropoiesis in HFD patients.

PMID- 28446126
TI  - CD44 silencing decreases the expression of stem cell-related factors induced by
      transforming growth factor beta1 and tumor necrosis factor alpha in lung cancer:
      Preliminary findings.
AB  - The mechanism underlying increased concentrations of cancer stem cell (CSC)
      associated factors in non-small cell lung cancer (NSCLC) cells treated with
      transforming growth factor beta1 (TGFbeta1) and tumor necrosis factor alpha
      (TNFalpha), is still not clear. The purpose of this study was to investigate the
      possible role of CD44 in the regulation of CSC-associated genes, by analyzing the
      effect of CD44 knockdown on their expression. A549, a NSCLC cell line that
      expresses CD44 antigen, was treated with TGFbeta1 and TNFalpha. Small-interfering
      ribonucleic acid (siRNA) that specifically targets the CD44 gene was used to
      knockdown the expression of CD44 in A549. The gene expressions of CD44, CXCR4,
      POU5F1 (octamer-binding transcription factor 4 [Oct4]), PROM1, NANOG, c-Myc,
      KLF4, and SOX2, as well as of CDH1 (E-cadherin), CDH2 (N-cadherin), VIM
      (vimentin), and FN1 (fibronectin) were analyzed in A549 cells by quantitative
      reverse transcription polymerase chain reaction (RT-qPCR). Cell morphology was
      observed using light microscopy. After TGFbeta1/TNFalpha treatment, increased
      expressions of CXCR4 and POU5F1 were detected. Silencing of CD44 gene expression
      was confirmed by RT-qPCR. The knockdown of CD44 decreased the CXCR4 and POU5F1
      gene expressions in TGFbeta1/TNFalpha-treated A549 cells. However, the silencing
      of CD44 did not affect the morphology of TGFbeta1/TNFalpha-treated A549 cells nor
      it reversed epithelial-mesenchymal transition (EMT) gene signature induced by
      TGFbeta1/TNFalpha in A549 cells. Our preliminary findings suggest that the CD44
      gene may have a role in regulating CXCR4 and POU5F1 gene expressions,
      independently of the EMT signaling pathway.

PMID- 28446127
TI  - Sample size and power determination when limited preliminary information is
      available.
AB  - BACKGROUND: We describe a novel strategy for power and sample size determination
      developed for studies utilizing investigational technologies with limited
      available preliminary data, specifically of imaging biomarkers. We evaluated
      diffuse optical spectroscopic imaging (DOSI), an experimental noninvasive imaging
      technique that may be capable of assessing changes in mammographic density.
      Because there is significant evidence that tamoxifen treatment is more effective
      at reducing breast cancer risk when accompanied by a reduction of breast density,
      we designed a study to assess the changes from baseline in DOSI imaging
      biomarkers that may reflect fluctuations in breast density in premenopausal women
      receiving tamoxifen. METHOD: While preliminary data demonstrate that DOSI is
      sensitive to mammographic density in women about to receive neoadjuvant
      chemotherapy for breast cancer, there is no information on DOSI in tamoxifen
      treatment. Since the relationship between magnetic resonance imaging (MRI) and
      DOSI has been established in previous studies, we developed a statistical
      simulation approach utilizing information from an investigation of MRI assessment
      of breast density in 16 women before and after treatment with tamoxifen to
      estimate the changes in DOSI biomarkers due to tamoxifen. RESULTS: Three sets of
      10,000 pairs of MRI breast density data with correlation coefficients of 0.5, 0.8
      and 0.9 were simulated and generated and were used to simulate and generate a
      corresponding 5,000,000 pairs of DOSI values representing water, ctHHB, and
      lipid. Minimum sample sizes needed per group for specified clinically-relevant
      effect sizes were obtained. CONCLUSION: The simulation techniques we describe can
      be applied in studies of other experimental technologies to obtain the important
      preliminary data to inform the power and sample size calculations.

PMID- 28446128
TI  - Erratum to: Genomic prediction using subsampling.

PMID- 28446129
TI  - Novel predictors of neurosyphilis among HIV-negative syphilis patients with
      neurological symptoms: an observational study.
AB  - BACKGROUND: Known predictors of neurosyphilis were mainly drawn from human
      immunodeficiency virus (HIV)-infected syphilis patients, which may not be
      applicable to HIV-negative populations as they have different characteristics,
      particularly those with neurological symptoms. This study aimed to identify novel
      predictors of HIV-negative symptomatic neurosyphilis (S-NS). METHODS: From June
      2005 to June 2015, 370 HIV-negative syphilis patients with neurological symptoms
      were recruited, consisting of 191 S-NS patients (including 123 confirmed
      neurosyphilis and 68 probable neurosyphilis patients) and 179 syphilis/non
      neurosyphilis (N-NS) patients. Clinical and laboratory characteristics of S-NS
      were compared with N-NS to identify factors predictive of S-NS. Serum rapid
      plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and their
      parallel testing format for screening S-NS were evaluated. RESULTS: The
      likelihood of S-NS was positively associated with the serum RPR and TPPA titers.
      The serum TPPA titers performed better than the serum RPR titers in screening S
      NS. The optimal cut-off points to recognize S-NS were serum RPR titer >=1:4 and
      serum TPPA titer >=1:2560 respectively. A parallel testing format of a serum RPR
      titer >=1:2 and serum TPPA titer >=1:1280 screened out 95.8% of S-NS and all
      confirmed cases of neurosyphilis. S-NS was independently associated with male
      sex, serum RPR titer >=1:4, serum TPPA titer >=1:2560, and elevated serum
      creatine kinase. Concurrence of these factors increased the likelihood of S-NS.
      CONCLUSIONS: Quantitation of serum TPPA is worthwhile and performs better than
      serum RPR in screening S-NS. Serum RPR, serum TPPA, male sex, and serum creatine
      kinase can predict S-NS. Moreover, patients with both a serum RPR titer <1:2 and
      a serum TPPA titer <1:1280 have a low probability of S-NS, suggesting that it is
      reasonable to reduce lumbar punctures in such individuals.

PMID- 28446130
TI  - A comparison of pediatric and adult CT organ dose estimation methods.
AB  - BACKGROUND: Computed Tomography (CT) contributes up to 50% of the medical
      exposure to the United States population. Children are considered to be at higher
      risk of developing radiation-induced tumors due to the young age of exposure and
      increased tissue radiosensitivity. Organ dose estimation is essential for
      pediatric and adult patient cancer risk assessment. The objective of this study
      is to validate the VirtualDose software in comparison to currently available
      software and methods for pediatric and adult CT organ dose estimation. METHODS:
      Five age groups of pediatric patients and adult patients were simulated by three
      organ dose estimators. Head, chest, abdomen-pelvis, and chest-abdomen-pelvis CT
      scans were simulated, and doses to organs both inside and outside the scan range
      were compared. For adults, VirtualDose was compared against ImPACT and CT-Expo.
      For pediatric patients, VirtualDose was compared to CT-Expo and compared to size
      based methods from literature. Pediatric to adult effective dose ratios were also
      calculated with VirtualDose, and were compared with the ranges of effective dose
      ratios provided in ImPACT. RESULTS: In-field organs see less than 60% difference
      in dose between dose estimators. For organs outside scan range or distributed
      organs, a five times' difference can occur. VirtualDose agrees with the size
      based methods within 20% difference for the organs investigated. Between
      VirtualDose and ImPACT, the pediatric to adult ratios for effective dose are
      compared, and less than 21% difference is observed for chest scan while more than
      40% difference is observed for head-neck scan and abdomen-pelvis scan. For
      pediatric patients, 2 cm scan range change can lead to a five times dose
      difference in partially scanned organs. CONCLUSIONS: VirtualDose is validated
      against CT-Expo and ImPACT with relatively small discrepancies in dose for organs
      inside scan range, while large discrepancies in dose are observed for organs
      outside scan range. Patient-specific organ dose estimation is possible using the
      size-based methods, and VirtualDose agrees with size-based method for the organs
      investigated. Careful range selection for CT protocols is necessary for organ
      dose optimization for pediatric and adult patients.

PMID- 28446131
TI  - The effectiveness of a monetary incentive offer on survey response rates and
      response completeness in a longitudinal study.
AB  - BACKGROUND: Achieving adequate response rates is an ongoing challenge for
      longitudinal studies. The World Trade Center Health Registry is a longitudinal
      health study that periodically surveys a cohort of ~71,000 people exposed to the
      9/11 terrorist attacks in New York City. Since Wave 1, the Registry has conducted
      three follow-up surveys (Waves 2-4) every 3-4 years and utilized various
      strategies to increase survey participation. A promised monetary incentive was
      offered for the first time to survey non-respondents in the recent Wave 4 survey,
      conducted 13-14 years after 9/11. METHODS: We evaluated the effectiveness of a
      monetary incentive in improving the response rate five months after survey
      launch, and assessed whether or not response completeness was compromised due to
      incentive use. The study compared the likelihood of returning a survey for those
      who received an incentive offer to those who did not, using logistic regression
      models. Among those who returned surveys, we also examined whether those
      receiving an incentive notification had higher rate of response completeness than
      those who did not, using negative binomial regression models and logistic
      regression models. RESULTS: We found that a $10 monetary incentive offer was
      effective in increasing Wave 4 response rates. Specifically, the $10 incentive
      offer was useful in encouraging initially reluctant participants to respond to
      the survey. The likelihood of returning a survey increased by 30% for those who
      received an incentive offer (AOR = 1.3, 95% CI: 1.1, 1.4), and the incentive
      increased the number of returned surveys by 18%. Moreover, our results did not
      reveal any significant differences on response completeness between those who
      received an incentive offer and those who did not. CONCLUSIONS: In the face of
      the growing challenge of maintaining a high response rate for the World Trade
      Center Health Registry follow-up surveys, this study showed the value of offering
      a monetary incentive as an additional refusal conversion strategy. Our findings
      also suggest that an incentive offer could be particularly useful near the end of
      data collection period when an immediate boost in response rate is needed.

PMID- 28446132
TI  - Pcsk5 is required in the early cranio-cardiac mesoderm for heart development.
AB  - BACKGROUND: Loss of proprotein convertase subtilisin/kexin type 5 (Pcsk5) results
      in multiple developmental anomalies including cardiac malformations, caudal
      regression, pre-sacral mass, renal agenesis, anteroposterior patterning defects,
      and tracheo-oesophageal and anorectal malformations, and is a model for
      VACTERL/caudal regression/Currarino syndromes (VACTERL association - Vertebral
      anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula and/or
      Esophageal atresia, Renal & Radial anomalies and Limb defects). RESULTS: Using
      magnetic resonance imaging (MRI), we examined heart development in mouse embryos
      with zygotic and cardiac specific deletion of Pcsk5. We show that conditional
      deletion of Pcsk5 in all epiblastic lineages recapitulates all developmental
      malformations except for tracheo-esophageal malformations. Using a conditional
      deletion strategy, we find that there is an essential and specific requirement
      for Pcsk5 in the cranio-cardiac mesoderm for cardiogenesis, but not for
      conotruncal septation or any other aspect of embryonic development. Surprisingly,
      deletion of Pcsk5 in cardiogenic or pharyngeal mesodermal progenitors that form
      later from the cranio-cardiac mesoderm does not affect heart development. Neither
      is Pcsk5 essential in the neural crest, which drives conotruncal septation.
      CONCLUSIONS: Our results suggest that Pcsk5 may have an essential and early role
      in the cranio-cardiac mesoderm for heart development. Alternatively, it is
      possible that Pcsk5 may still play a critical role in Nkx2.5-expressing cardiac
      progenitors, with persistence of mRNA or protein accounting for the lack of
      effect of deletion on heart development.

PMID- 28446134
TI  - Assessment of perioperative minute ventilation in obese versus non-obese patients
      with a non-invasive respiratory volume monitor.
AB  - BACKGROUND: Monitoring the adequacy of spontaneous breathing is a major patient
      safety concern in the post-operative setting. Monitoring is particularly
      important for obese patients, who are at a higher risk for post-surgical
      respiratory complications and often have increased metabolic demand due to excess
      weight. Here we used a novel, noninvasive Respiratory Volume Monitor (RVM) to
      monitor ventilation in both obese and non-obese orthopedic patients throughout
      their perioperative course, in order to develop better monitoring strategies.
      METHODS: We collected respiratory data from 62 orthopedic patients undergoing
      elective joint replacement surgery under general anesthesia using a bio-impedance
      based RVM with an electrode PadSet placed on the thorax. Patients were stratified
      into obese (BMI >= 30) and non-obese cohorts and minute ventilation (MV) at
      various perioperative time points was compared against each patient's predicted
      minute ventilation (MVPRED) based on ideal body weight (IBW) and body surface
      area (BSA). The distributions of MV measurements were also compared across obese
      and non-obese cohorts. RESULTS: Obese patients had higher MV than the non-obese
      patients before, during, and after surgery. Measured MV of obese patients was
      significantly higher than their MVPRED from IBW formulas, with BSA-based MVPRED
      being a closer estimate. Obese patients also had greater variability in MV post
      operatively when treated with standard opioid dosing. CONCLUSIONS: Our study
      demonstrated that obese patients have greater variability in ventilation post
      operatively when treated with standard opioid doses, and despite overall higher
      ventilation, many of them are still at risk for hypoventilation. BSA-based MVPRED
      formulas may be more appropriate than IBW-based ones when estimating the
      respiratory demand of obese patients. The RVM allows for the continuous and non
      invasive assessment of respiratory function in both obese and non-obese patients.

PMID- 28446135
TI  - Comparison of rapid immunoassays for rupture of fetal membranes.
AB  - BACKGROUND: Rupture of membranes (ROM) before the onset of uterine contractions,
      particularly in pregnancies less than 37 weeks gestational age, is a common
      diagnostic problem in obstetrical practice. Timely detection of ROM is vital to
      support gestational age-specific interventions to optimize perinatal outcomes and
      minimize the risk of serious complications such as preterm delivery, fetal
      distress and maternal/fetal infections. Rapid bedside immunoassay tests designed
      to detect amniotic fluid proteins in cervicovaginal fluids have emerged as
      valuable clinical tools to provide timely ROM diagnosis. METHODS: In this
      prospective observational study, two commercially-available immunoassay tests
      (ROM Plus(r), AmniSure(r)) were evaluated concurrently in 111 pregnant women who
      presented with the chief complaint of ROM. Immunoassay results were compared to
      clinical parameters for determining ROM via comprehensive, retrospective clinical
      chart review. Diagnostic performance characteristics were calculated including
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and accuracy. RESULTS: Overall, diagnostic performance
      characteristics were robust and similar between ROM Plus(r) and AmniSure(r),
      respectively: sensitivity (96.4 and 89.3%), specificity (98.8 and 100%), PPV
      (96.4 and 100%), NPV (98.8% and 96.5) and accuracy (98.2 and 97.3%). For term
      patients (>=37 weeks gestation), the sensitivities were 93.8 and 81.3% and
      specificities were 97.1 and 100% for ROM Plus(r) and AmniSure(r), respectively.
      For preterm patients (<37 weeks gestation), both immunoassay tests provided exact
      concordance with clinical confirmation of ROM resulting in 100% diagnostic
      accuracy. CONCLUSIONS: Both rapid immunoassay tests provided similarly excellent
      diagnostic accuracy for the rapid detection of ROM with only two discrepant
      results for ROM Plus(r) and three discrepant results for AmniSure(r) compared to
      clinical confirmation. The findings from this study recommend these tests for
      pregnant women presenting with suspected ROM to guide correct clinical management
      decisions to improve obstetrical and neonatal outcomes. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02208011 (1 August 2014).

PMID- 28446133
TI  - Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide
      in Wistar rats.
AB  - BACKGROUND: The present study sought to evaluate the efficacy of N-acetylcysteine
      amide (NACA) eye drops in reversing the cataract formation induced by sodium
      selenite in male Wistar rat pups. METHODS: Forty male Wistar rat pups were
      randomly divided into a control group, an N-acetylcysteine amide-only group, a
      sodium selenite-induced cataract group, and a NACA-treated sodium selenite
      induced cataract group. Sodium selenite was injected intraperitoneally on
      postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally
      on postpartum days 9, 11, and 13 in the respective groups. Cataracts were
      evaluated at the end of week 2 (postpartum day 14) when the rat pups opened their
      eyes. N-acetylcysteine amide eye drops were administered beginning on week 3
      until the end of week 4 (postpartum days 15 to 30), and the rats were sacrificed
      at the end of week 4. Lenses were isolated and examined for oxidative stress
      parameters such as glutathione, lipid peroxidation, and calcium levels along with
      the glutathione reductase and thioltransferase enzyme activities. Casein
      zymography and Western blot of m-calpain were performed using the water soluble
      fraction of lens proteins. RESULTS: Morphological examination of the lenses in
      the NACA-treated group indicated that NACA was able to reverse the cataract
      grade. In addition, glutathione level, thioltransferase activity, m-calpain
      activity, and m-calpain level (as assessed by Western blot) were all
      significantly higher in the NACA-treated group than in the sodium selenite
      induced cataract group. Furthermore, sodium selenite- injected rat pups had
      significantly higher levels of malondialdehyde, glutathione reductase enzyme
      activity, and calcium levels, which were reduced to control levels upon treatment
      with NACA. CONCLUSIONS: The data suggest that NACA has the potential to
      significantly improve vision and decrease the burden of cataract-related loss of
      function. Prevention and reversal of cataract formation could have a global
      impact. Development of pharmacological agents like NACA may eventually prevent
      cataract formation in high-risk populations and may prevent progression of early
      stage cataracts. This brings a paradigm shift from expensive surgical treatment
      of cataracts to relatively inexpensive prevention of vision loss.

PMID- 28446136
TI  - First mutation in the FSHR cytoplasmic tail identified in a non-pregnant woman
      with spontaneous ovarian hyperstimulation syndrome.
AB  - BACKGROUND: Spontaneous ovarian hyperstimulation syndrome (sOHSS) is a rare event
      occurring mostly during natural pregnancy. Among described etiologies, some
      activating mutations of FSH receptor (FSHR) have been identified. CASE
      PRESENTATION: We report hereby the case of a non-pregnant women with three
      episodes of sOHSS. Hormonal evaluation was normal and no pituitary adenoma was
      detected. However, genetic analysis identified a novel heterozygous FSHR mutation
      (c.1901 G > A). This R634H mutation is the first described in the cytoplasmic
      tail of the receptor. Functional analysis failed to reveal constitutive activity
      of the mutant but a decreased cAMP production in response to FSH. The weak
      activity of this mutant is correlated with a markedly reduced cell surface
      expression. CONCLUSION: Pathophysiology of non gestationnal sOHSS is still ill
      established. The molecular characterization of this new mutant indicates that it
      might not be at play. Therefore, further investigations are needed to improve
      knowledge of the molecular mechanism of this syndrome.

PMID- 28446137
TI  - Progressive cutaneous Cryptococcosis complicated with meningitis in a myasthenia
      gravis patient on long-term immunosuppressive therapy - a case report.
AB  - BACKGROUND: Cryptococcosis is an opportunistic infection caused by the
      encapsulated yeast Cryptococcus neoformans and most remarkably manifests in HIV
      infected individuals, especially in the settings of very low CD4 count.
      Development of cryptococcosis in HIV-uninfected individuals is exceedingly rare
      and usually signifies a marked immunodeficiency. Cryptococcosis in association
      with myasthenia gravis or thymoma has been previously documented in only very few
      cases in the literature. CASE PRESENTATION: We reported a complicated case of
      severe cutaneous cryptococcosis in a 39-year-old Vietnamese male patient with
      myasthenia gravis on long-term immunosuppressive therapy. The patient presented
      with a five month history of recurrent and progressive skin lesions that later on
      progressed into cryptococcal meningitis. CONCLUSION: Through this case, we aimed
      to emphasize the importance of including cutaneous cryptococcosis in the
      differential diagnosis of cutaneous lesions in patients on chronic
      immunosuppressive therapy. The cutaneous manifestations of cryptococcosis can be
      the first clue for a disseminated disease, which makes early recognition crucial
      and life-saving.

PMID- 28446138
TI  - Assessing the complexity of interventions within systematic reviews: development,
      content and use of a new tool (iCAT_SR).
AB  - BACKGROUND: Health interventions fall along a spectrum from simple to more
      complex. There is wide interest in methods for reviewing 'complex interventions',
      but few transparent approaches for assessing intervention complexity in
      systematic reviews. Such assessments may assist review authors in, for example,
      systematically describing interventions and developing logic models. This paper
      describes the development and application of the intervention Complexity
      Assessment Tool for Systematic Reviews (iCAT_SR), a new tool to assess and
      categorise levels of intervention complexity in systematic reviews. METHODS: We
      developed the iCAT_SR by adapting and extending an existing complexity assessment
      tool for randomized trials. We undertook this adaptation using a consensus
      approach in which possible complexity dimensions were circulated for feedback to
      a panel of methodologists with expertise in complex interventions and systematic
      reviews. Based on these inputs, we developed a draft version of the tool. We then
      invited a second round of feedback from the panel and a wider group of systematic
      reviewers. This informed further refinement of the tool. RESULTS: The tool
      comprises ten dimensions: (1) the number of active components in the
      intervention; (2) the number of behaviours of recipients to which the
      intervention is directed; (3) the range and number of organizational levels
      targeted by the intervention; (4) the degree of tailoring intended or flexibility
      permitted across sites or individuals in applying or implementing the
      intervention; (5) the level of skill required by those delivering the
      intervention; (6) the level of skill required by those receiving the
      intervention; (7) the degree of interaction between intervention components; (8)
      the degree to which the effects of the intervention are context dependent; (9)
      the degree to which the effects of the interventions are changed by recipient or
      provider factors; (10) and the nature of the causal pathway between intervention
      and outcome. Dimensions 1-6 are considered 'core' dimensions. Dimensions 7-10 are
      optional and may not be useful for all interventions. CONCLUSIONS: The iCAT_SR
      tool facilitates more in-depth, systematic assessment of the complexity of
      interventions in systematic reviews and can assist in undertaking reviews and
      interpreting review findings. Further testing of the tool is now needed.

PMID- 28446139
TI  - De novo assembly of highly polymorphic metagenomic data using in situ generated
      reference sequences and a novel BLAST-based assembly pipeline.
AB  - BACKGROUND: The accuracy of metagenomic assembly is usually compromised by high
      levels of polymorphism due to divergent reads from the same genomic region
      recognized as different loci when sequenced and assembled together. A viral
      quasispecies is a group of abundant and diversified genetically related viruses
      found in a single carrier. Current mainstream assembly methods, such as Velvet
      and SOAPdenovo, were not originally intended for the assembly of such
      metagenomics data, and therefore demands for new methods to provide accurate and
      informative assembly results for metagenomic data. RESULTS: In this study, we
      present a hybrid method for assembling highly polymorphic data combining the
      partial de novo-reference assembly (PDR) strategy and the BLAST-based assembly
      pipeline (BBAP). The PDR strategy generates in situ reference sequences through
      de novo assembly of a randomly extracted partial data set which is subsequently
      used for the reference assembly for the full data set. BBAP employs a greedy
      algorithm to assemble polymorphic reads. We used 12 hepatitis B virus
      quasispecies NGS data sets from a previous study to assess and compare the
      performance of both PDR and BBAP. Analyses suggest the high polymorphism of a
      full metagenomic data set leads to fragmentized de novo assembly results, whereas
      the biased or limited representation of external reference sequences included
      fewer reads into the assembly with lower assembly accuracy and variation
      sensitivity. In comparison, the PDR generated in situ reference sequence
      incorporated more reads into the final PDR assembly of the full metagenomics data
      set along with greater accuracy and higher variation sensitivity. BBAP assembly
      results also suggest higher assembly efficiency and accuracy compared to other
      assembly methods. Additionally, BBAP assembly recovered HBV structural variants
      that were not observed amongst assembly results of other methods. Together,
      PDR/BBAP assembly results were significantly better than other compared methods.
      CONCLUSIONS: Both PDR and BBAP independently increased the assembly efficiency
      and accuracy of highly polymorphic data, and assembly performances were further
      improved when used together. BBAP also provides nucleotide frequency information.
      Together, PDR and BBAP provide powerful tools for metagenomic data studies.

PMID- 28446140
TI  - Measurement properties of the Danish version of the Awareness and Beliefs about
      Cancer (ABC) measure.
AB  - BACKGROUND: The International Cancer Benchmarking Partnership aims to study
      international differences in cancer survival and the possible causes.
      Participating countries are Australia, Canada, Norway, Sweden, Denmark and the UK
      and a particular focus area is differences in awareness and beliefs about cancer.
      In this connection, the Awareness and Beliefs about Cancer (ABC) measure has been
      translated into multiple languages. The aim of this study is to appraise the
      translation process and measurement properties of the Danish version of the ABC
      measure. METHODS: The translation process included forward and backward
      translations and a pilot-test. Data quality was assessed using survey data from
      3000 Danish respondents and content validity indexes were calculated based on
      judgments from ten academic researchers. Construct validity was determined by a
      confirmative factor analysis (CFA) and exploratory factor analyses (EFA) using
      survey data and a known group comparison analysis including 56 persons. Test
      retest reliability was assessed based on responses from 123 person whom completed
      the interview twice with an interval of 2-3 weeks. RESULTS: The translation
      process resulted in a Danish ABC measure conceptually equivalent to the English
      ABC measure. Data quality was acceptable in relation to non-response to
      individual items which was maximum 0.3%, but the percentage of respondents
      answering 'don't know' was above 3% for 16 out of 48 items. Content validity
      indexes showed that items adequately reflected and represented the constructs to
      be measured (item content validity indexes: 0.9-1.0; construct content validity
      indexes: 0.8-1.0). The hypothesised factor structure could not be replicated by a
      CFA, but EFA on each individual subscale showed that six out of seven subscales
      were unidimensional. The ABC measure discriminated well between non-medical
      academics and medical academics, but had some difficulties in discriminating
      between educational groups. Test-retest reliability was moderate to substantial
      for most items. CONCLUSIONS: The Danish ABC measure is a useful measurement that
      is accepted and understood by the target group and with accepted measurement
      criteria for content validity and test-retest reliability. Future studies may
      further explore the factorial structure of the ABC measure and should focus on
      improving the response categories.

PMID- 28446141
TI  - A mobile application of breast cancer e-support program versus routine Care in
      the treatment of Chinese women with breast cancer undergoing chemotherapy: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Women with breast cancer undergoing chemotherapy suffer from a number
      of symptoms and report receiving inadequate support from health care
      professionals. Innovative and easily accessible interventions are lacking. Breast
      Cancer e-Support is a mobile Application program (App) that provides patients
      with individually tailored information and a support group of peers and health
      care professionals. Breast Cancer e-Support aims to promote women's self
      efficacy, social support and symptom management, thus improving their quality of
      life and psychological well-being. METHODS: A single-blinded, multi-centre,
      randomised, 6-month, parallel-group superiority design will be used. Based on
      Bandura's self-efficacy theory and the social exchange theory, Breast Cancer e
      Support has four modules: 1) a Learning forum; 2) a Discussion forum; 3) an Ask
      the-Expert forum; and 4) a Personal Stories forum. Women with breast cancer (n =
      108) who are commencing chemotherapy will be recruited from two university
      affiliated hospitals in China. They will be randomly assigned to either control
      group that receives routine care or intervention group that receives routine care
      plus access to Breast Cancer e-Support program during their four cycles of
      chemotherapy. Self-efficacy, social support, symptom distress, quality of life,
      and anxiety and depression will be measured at baseline, then one week and 12
      weeks post-intervention. DISCUSSION: This is the first study of its kind in China
      to evaluate the use of a mobile application intervention with a rigorous research
      design and theoretical framework. This study will contribute to evidence
      regarding the effectiveness of a theory-based mobile application to support women
      with breast cancer undergoing chemotherapy. The results should provide a better
      understanding of the role of self-efficacy and social support in reducing symptom
      distress and of the credibility of using a theoretical framework to develop
      internet-based interventions. The results will provide evidence to support the
      implementation of an innovative and easily accessible intervention that enhances
      health outcomes. TRIAL REGISTRATION: ACTRN: ACTRN12616000639426 , Registered 17
      May, 2016.

PMID- 28446142
TI  - Differences in peripheral myelin antigen-specific T cell responses and T memory
      subsets in atypical versus typical CIDP.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is presented
      by a large heterogeneity of clinical phenotypes. Around 50% of patients suffer
      from typical CIDP and show better therapy response than atypical variants. The
      goal of our study was to search for cellular immunological differences in typical
      versus atypical CIDP in comparison to controls. METHODS: We evaluated 26 (9
      typical, 17 atypical) patients with mainly active-unstable CIDP using clinical
      and immunological examinations (enzyme-linked immunospot assay ELISPOT,
      fluorescence-activated cell sorting FACS) in comparison to 28 healthy, age
      matched controls (HC). Typical or atypical CIDP measurements were compared with
      HC using Kruskal-Wallis test. RESULTS: Atypical CIDP patients showed increased
      frequencies of T cell subsets, especially CD4+ effector memory T cells (TEM) and
      CD4+ central memory T cells (TCM) as well as a tendency of higher T cell
      responses against the peripheral myelin antigens of PMP-22, P2, P0 and MBP
      peptides compared to typical CIDP. Searching for novel auto-antigens, we found
      that T cell responses against P0 180-199 as well as MBP 82-100 were significantly
      elevated in atypical CIDP patients vs. HC. CONCLUSIONS: Our results indicate
      differences in underlying T cell responses between atypical and typical CIDP
      characterized by a higher peripheral myelin antigen-specific T cell responses as
      well as a specific altered CD4+ memory compartment in atypical CIDP. Larger multi
      center studies study are warranted in order to characterize T cell auto
      reactivity in atypical CIDP subgroups in order to establish immunological markers
      as a diagnostic tool.

PMID- 28446143
TI  - IgG4-related membranous glomerulonephritis and generalized lymphadenopathy
      without pancreatitis: a case report.
AB  - BACKGROUND: IgG4-related disease is a recently described pathologic entity. This
      is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4
      related disease. Such a kidney involvement is quite peculiar and has only been
      described a few times recently. Renal biopsy showed a glomerular involvement with
      membranous glomerulonephritis in association with a tubulo-interstitial
      nephropathy. Moreover, the patient was not suffering from pancreatitis. CASE
      PRESENTATION: The patient is a middle-aged man of Moroccan origin. He has
      developed recurrent episodes of diffuse lymphadenopathies, renal failure and
      nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis.
      DISCUSSION AND CONCLUSION: The diagnostic approach of this atypical presentation
      is discussed in this case report as well as diagnostic criteria, therapeutic
      strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related
      membranous glomerulonephritis is a well-established cause of membranous
      glomerulonephritis. It must be sought after in every patient with a previous
      diagnosis of IgG4-related disease and in every patient with this histological
      finding on renal biopsy. Corticoids are still the first-line treatment of IgG4
      related disease. New therapeutic strategies are needed to avoid glucocorticoids
      long term side-effects. Interestingly, the patient was prescribed
      cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia.
      This treatment had a very good impact on his IgG4-related disease.

PMID- 28446144
TI  - Association of physical activity and appetite with visual function related to
      driving competence in older adults.
AB  - BACKGROUND: Older people are at greater risk of traffic accidents, partially
      because of age-related declines in visual function, including reduced useful
      field of view (UFOV). However, lifestyle factors which cause age-related decline
      in UFOV remain poorly understood. We conducted a study to investigate whether
      physical activity and appetite status were related to UFOV test performance in
      healthy older adults. METHODS: Thirty community-dwelling older people (age 68.6
      +/- 3.1 years, 15 females) were enrolled in this study. Each participant
      completed the Council on Nutrition appetite questionnaire (CNAQ) and a UFOV test.
      They then wore a tri-axial accelerometer (Active style Pro HJA-350IT) for 3-6
      consecutive days to objectively measure their PA in free-living conditions.
      RESULTS: Longer time spent in vigorous physical activity was significantly
      associated with better UFOV test performance when adjusted for age and
      accelerometer wear time (non-locomotive: r = -0.435, locomotive: r = -0.449; n =
      25). In addition, male, but not female, participants with a higher CNAQ score had
      significantly better UFOV test performance in both an unadjusted model (r = 
      0.560; n = 15) and a model adjusted for age (r = -0.635; n = 15). CONCLUSIONS:
      The results suggest that appetite status among males and time spent in high
      intensity PA are associated with visual function related to driving competence in
      older adults.

PMID- 28446145
TI  - Genome-wide analysis of ATP-binding cassette (ABC) transporters in the
      sweetpotato whitefly, Bemisia tabaci.
AB  - BACKGROUND: ABC transporter superfamily is one of the largest and ubiquitous
      groups of proteins. Because of their role in detoxification, insect ABC
      transporters have gained more attention in recent years. In this study, we
      annotated ABC transporters from a newly sequenced sweetpotato whitefly genome.
      Bemisia tabaci Q biotype is an emerging global invasive species that has caused
      extensive damages to field crops as well as ornamental plants. RESULTS: A total
      of 55 ABC transporters containing all eight described subfamilies (A to H) were
      identified in the B. tabaci Q genome, including 8 ABCAs, 3 ABCBs, 6 ABCCs, 2
      ABCDs, 1 ABCE, 3 ABCFs, 23 ABCGs and 9 ABCHs. In comparison to other species,
      subfamilies G and H in both phloem- and blood-sucking arthropods are expanded.
      The temporal expression profiles of these 55 ABC transporters throughout B.
      tabaci developmental stages and their responses to imidacloprid, a neonicotinoid
      insecticide, were investigated using RNA-seq analysis. Furthermore, the mRNA
      expression of 24 ABC transporters (44% of the total) representing all eight
      subfamilies was confirmed by the quantitative real-time PCR (RT-qPCR).
      Furthermore, mRNA expression levels estimated by RT-qPCR and RNA-seq analyses
      were significantly correlated (r = 0.684, p < 0.01). CONCLUSIONS: It is the first
      genome-wide analysis of the entire repertoire of ABC transporters in B. tabaci.
      The identification of these ABC transporters, their temporal expression profiles
      during B. tabaci development, and their response to a neonicotinoid insecticide
      lay the foundation for functional genomic understanding of their contribution to
      the invasiveness of B. tabaci.

PMID- 28446146
TI  - Flow cytometry sorting of nuclei enables the first global characterization of
      Paramecium germline DNA and transposable elements.
AB  - BACKGROUND: DNA elimination is developmentally programmed in a wide variety of
      eukaryotes, including unicellular ciliates, and leads to the generation of
      distinct germline and somatic genomes. The ciliate Paramecium tetraurelia harbors
      two types of nuclei with different functions and genome structures. The
      transcriptionally inactive micronucleus contains the complete germline genome,
      while the somatic macronucleus contains a reduced genome streamlined for gene
      expression. During development of the somatic macronucleus, the germline genome
      undergoes massive and reproducible DNA elimination events. Availability of both
      the somatic and germline genomes is essential to examine the genome changes that
      occur during programmed DNA elimination and ultimately decipher the mechanisms
      underlying the specific removal of germline-limited sequences. RESULTS: We
      developed a novel experimental approach that uses flow cell imaging and flow
      cytometry to sort subpopulations of nuclei to high purity. We sorted vegetative
      micronuclei and macronuclei during development of P. tetraurelia. We validated
      the method by flow cell imaging and by high throughput DNA sequencing. Our work
      establishes the proof of principle that developing somatic macronuclei can be
      sorted from a complex biological sample to high purity based on their size, shape
      and DNA content. This method enabled us to sequence, for the first time, the
      germline DNA from pure micronuclei and to identify novel transposable elements.
      Sequencing the germline DNA confirms that the Pgm domesticated transposase is
      required for the excision of all ~45,000 Internal Eliminated Sequences.
      Comparison of the germline DNA and unrearranged DNA obtained from PGM-silenced
      cells reveals that the latter does not provide a faithful representation of the
      germline genome. CONCLUSIONS: We developed a flow cytometry-based method to
      purify P. tetraurelia nuclei to high purity and provided quality control with
      flow cell imaging and high throughput DNA sequencing. We identified 61 germline
      transposable elements including the first Paramecium retrotransposons. This
      approach paves the way to sequence the germline genomes of P. aurelia sibling
      species for future comparative genomic studies.

PMID- 28446147
TI  - Serum albumin, a good indicator of persistent organ failure in acute
      pancreatitis.
AB  - BACKGROUND: To evaluate the predictive value of serum albumin (ALB) for
      persistent organ failure (POF) in acute pancreatitis (AP). METHODS: We selected
      158 patients with AP in this retrospective study from Jan.1st, 2015 to Dec.31st,
      2015. Forty-six patients were diagnosed with POF. All the values of laboratory
      parameters were measured upon admission to hospital. And 48 h after admission, we
      examined serum albumin of each patient again, called 'ALB2'. Uni-and multi
      variate logistic regression were used to evaluate the impact of ALB to predict
      POF. RESULTS: The median age of the whole population was 48 years and 53.8% were
      male. The admission-time albumin of AP patients with POF was distinctly lower
      than patients without POF (28.9 (25.3-33.1) g/L vs. 38.5 (34.0-40.1) g/L, p <
      0.001). In uni-variate analysis, WBC, PT, GLU, LDH, ALB, ALB2, BUN, Ca, HDL-C and
      Ranson were significantly associated with POF. After multivariate regression, ALB
      remained an independent prognostic factor for POF in AP (OR: 0.748, 95%CI: 0.645
      0.868; p < 0.05). The AUC for ALB is 0.873 (0.808, 0.938), even larger than that
      for Ranson, 0.845 (0.634, 0.913). CONCLUSIONS: We identified serum albumin
      predictive to persistent organ failure in acute pancreatitis.

PMID- 28446148
TI  - Circumpapillary retinal nerve fiber layer thickness, anterior lamina cribrosa
      depth, and lamina cribrosa thickness in neovascular glaucoma secondary to
      proliferative diabetic retinopathy: a cross-sectional study.
AB  - BACKGROUND: To compare the lamina cribrosa between eyes with and without
      neovascular glaucoma (NVG) using enhanced depth imaging spectral-domain optical
      coherence tomography. METHODS: Forty-six patients with proliferative diabetic
      retinopathy were enrolled in this cross-sectional study. The patients were
      divided into two groups based on the absence or presence of NVG (the non-NVG
      group and the NVG group, respectively). The intraocular pressure (IOP),
      circumpapillary retinal nerve fiber layer (cpRNFL) thickness, anterior lamina
      cribrosa depth (ALD), and laminar thickness (LT) were compared between the
      groups. RESULTS: In the non-NVG group, the mean age was 66.2 +/- 2.4 (mean +/-
      standard error) years, mean maximum IOP was 18.8 +/- 1.8 mmHg, mean cpRNFL
      thickness was 91.2 +/- 3.9 MUm, mean ALD was 407.0 +/- 22.9 MUm, and mean LT was
      155.0 +/- 4.7 MUm. In the NVG group, the mean age was 61.4 +/- 2.1 years, mean
      maximum IOP was 33.1 +/- 1.6 mmHg, mean cpRNFL thickness was 73.6 +/- 3.4 MUm,
      mean ALD was 403.9 +/- 20.1 MUm, and mean LT was 156.9 +/- 4.2 MUm. The IOP was
      significantly higher and the cpRNFL was significantly thinner in the NVG group (P
      < 0.001 and P = 0.002, respectively). However, the age, ALD, and LT were not
      statistically different between the groups (P = 0.151, 0.919, and 0.757,
      respectively). CONCLUSIONS: Although the cpRNFL was thinner, the structure of the
      lamina cribrosa was unchanged in the NVG eyes. Axonal loss of the retinal
      ganglion cells in NVG patients was prior to lamina cribrosa deformation.

PMID- 28446149
TI  - Effect of genetic variants and traits related to glucose metabolism and their
      interaction with obesity on breast and colorectal cancer risk among
      postmenopausal women.
AB  - BACKGROUND: Impaired glucose metabolism-related genetic variants and traits
      likely interact with obesity and related lifestyle factors, influencing
      postmenopausal breast and colorectal cancer (CRC), but their interconnected
      pathways are not fully understood. By stratifying via obesity and lifestyles, we
      partitioned the total effect of glucose metabolism genetic variants on cancer
      risk into two putative mechanisms: 1) indirect (risk-associated glucose
      metabolism genetic variants mediated by glucose metabolism traits) and 2) direct
      (risk-associated glucose metabolism genetic variants through pathways other than
      glucose metabolism traits) effects. METHOD: Using 16 single-nucleotide
      polymorphisms (SNPs) associated with glucose metabolism and data from 5379
      postmenopausal women in the Women's Health Initiative Harmonized and Imputed
      Genome-Wide Association Studies, we retrospectively assessed the indirect and
      direct effects of glucose metabolism-traits (fasting glucose, insulin, and
      homeostatic model assessment-insulin resistance [HOMA-IR]) using two quantitative
      tests. RESULTS: Several SNPs were associated with breast cancer and CRC risk, and
      these SNP-cancer associations differed between non-obese and obese women. In both
      strata, the direct effect of cancer risk associated with the SNP accounted for
      the majority of the total effect for most SNPs, with roughly 10% of cancer risk
      due to the SNP that was from an indirect effect mediated by glucose metabolism
      traits. No apparent differences in the indirect (glucose metabolism-mediated)
      effects were seen between non-obese and obese women. It is notable that among
      obese women, 50% of cancer risk was mediated via glucose metabolism trait, owing
      to two SNPs: in breast cancer, in relation to GCKR through glucose, and in CRC,
      in relation to DGKB/TMEM195 through HOMA-IR. CONCLUSIONS: Our findings suggest
      that glucose metabolism genetic variants interact with obesity, resulting in
      altered cancer risk through pathways other than those mediated by glucose
      metabolism traits.

PMID- 28446151
TI  - Novel mutation in the SLC12A3 gene in a Sri Lankan family with Gitelman syndrome
      & coexistent diabetes: a case report.
AB  - BACKGROUND: Gitelman syndrome (GS) is a rare autosomal recessively inherited salt
      wasting tubulopathy associated with mutations in the SLC12A3 gene, which encodes
      for NaCl cotransporter (NCC) in the kidney. CASE PRESENTATION: In this report, we
      describe two siblings from a Sri Lankan non-consanguineous family presenting with
      hypokalaemia associated with renal potassium wasting, hypomagnesemia,
      hypocalciuria and hypereninemic hyperaldosteronism with normal blood pressure.
      Genetic testing showed that both were homozygotes for a novel missense mutation
      in exon 10 of the SLC12A3 gene [NM_000339.2, c.1276A > T; p.N426Y], which has not
      previously been reported in the literature in association with GS. Their mother
      was a heterozygous carrier for the same mutation. The father was not alive at the
      time of testing. This novel mutation extends the spectrum of known SLC12A3 gene
      mutations and further supports the allelic heterogeneity of GS. Interestingly
      both siblings had young onset Diabetes with strong family history. CONCLUSION:
      These findings have implications in providing appropriate genetic counseling to
      the family with regard to the risk associated with inbreeding, the detection of
      carrier/presymptomatic relatives. It further expands the known spectrum of
      genotypic and phenotypic characteristics of Gitelman syndrome.

PMID- 28446150
TI  - Signatures of co-evolutionary host-pathogen interactions in the genome of the
      entomopathogenic nematode Steinernema carpocapsae.
AB  - BACKGROUND: The entomopathogenic nematode Steinernema carpocapsae has been used
      worldwide as a biocontrol agent for insect pests, making it an interesting model
      for understanding parasite-host interactions. Two models propose that these
      interactions are co-evolutionary processes in such a way that equilibrium is
      never reached. In one model, known as "arms race", new alleles in relevant genes
      are fixed in both host and pathogens by directional positive selection, producing
      recurrent and alternating selective sweeps. In the other model, known as"trench
      warfare", persistent dynamic fluctuations in allele frequencies are sustained by
      balancing selection. There are some examples of genes evolving according to both
      models, however, it is not clear to what extent these interactions might alter
      genome-level evolutionary patterns and intraspecific diversity. Here we
      investigate some of these aspects by studying genomic variation in S. carpocapsae
      and other pathogenic and free-living nematodes from phylogenetic clades IV and V.
      RESULTS: To look for signatures of an arms-race dynamic, we conducted massive
      scans to detect directional positive selection in interspecific data. In free
      living nematodes, we detected a significantly higher proportion of genes with
      sites under positive selection than in parasitic nematodes. However, in these
      genes, we found more enriched Gene Ontology terms in parasites. To detect
      possible effects of dynamic polymorphisms interactions we looked for signatures
      of balancing selection in intraspecific genomic data. The observed distribution
      of Tajima's D values in S. carpocapsae was more skewed to positive values and
      significantly different from the observed distribution in the free-living
      Caenorhabditis briggsae. Also, the proportion of significant positive values of
      Tajima's D was elevated in genes that were differentially expressed after
      induction with insect tissues as compared to both non-differentially expressed
      genes and the global scan. CONCLUSIONS: Our study provides a first portrait of
      the effects that lifestyle might have in shaping the patterns of selection at the
      genomic level. An arms-race between hosts and pathogens seems to be affecting
      specific genetic functions but not necessarily increasing the number of
      positively selected genes. Trench warfare dynamics seem to be acting more
      generally in the genome, likely focusing on genes responding to the interaction,
      rather than targeting specific genetic functions.

PMID- 28446152
TI  - Differential host gene responses from infection with neurovirulent and partially
      neurovirulent strains of Venezuelan equine encephalitis virus.
AB  - BACKGROUND: Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the
      family Togaviridae. VEEV causes a bi-phasic illness in mice where primary
      replication in lymphoid organs is followed by entry into the central nervous
      system (CNS). The CNS phase of infection is marked by encephalitis and large
      scale neuronal death ultimately resulting in death. Molecular determinants of
      VEEV neurovirulence are not well understood. In this study, host gene expression
      response to highly neurovirulent VEEV (V3000 strain) infection was compared with
      that of a partially neurovirulent VEEV (V3034 strain) to identify host factors
      associated with VEEV neurovirulence. METHODS: Whole genome microarrays were
      performed to identify the significantly modulated genes. Microarray observations
      were classified into three categories i.e., genes that were similarly modulated
      against both V3000 and V3034 infections, and genes that were uniquely modulated
      in infection with V3034 or V3000. Histologic sections of spleen and brain were
      evaluated by hematoxylin and eosin stains from all the mice. RESULTS: V3000
      infection induced a greater degree of pathology in both the spleen and brain
      tissue of infected mice compared to V3034 infection. Genes commonly modulated in
      the spleens after V3000 or V3034 infection were associated with innate immune
      responses, inflammation and antigen presentation, however, V3000 induced a gene
      response profile that suggests a stronger inflammatory and apoptotic response
      compared to V3034. In the brain, both the strains of VEEV induced an innate
      immune response reflected by an upregulation of the genes involved in antigen
      presentation, interferon response, and inflammation. Similar to the spleen, V3000
      was found to induce a stronger inflammatory response than V3034 in terms of
      induction of pro-inflammatory genes and associated pathways. Ccl2, Ccl5, Ccl6,
      and Ly6 were uniquely upregulated in V3000 infected mouse brains and correlated
      with the extensive inflammation observed in the brain. CONCLUSION: The common
      gene profile identified from V3000 and V3034 exposure can help in understanding a
      generalized host response to VEEV infection. Inflammatory genes that were
      uniquely identified in mouse brains with V3000 infection will help in better
      understanding the lethal neurovirulence of VEEV. Future studies are needed to
      explore the roles played by the genes identified in VEEV induced encephalitis.

PMID- 28446153
TI  - Acceleration and suppression of resistance development by antibiotic
      combinations.
AB  - BACKGROUND: The emergence and spread of antibiotic resistance in bacteria is
      becoming a global public health problem. Combination therapy, i.e., the
      simultaneous use of multiple antibiotics, is used for long-term treatment to
      suppress the emergence of resistant strains. However, the effect of the
      combinatorial use of multiple drugs on the development of resistance remains
      elusive, especially in a quantitative assessment. RESULTS: To understand the
      evolutionary dynamics under combination therapy, we performed laboratory
      evolution of Escherichia coli under simultaneous addition of two-drug
      combinations. We demonstrated that simultaneous addition of a certain
      combinations of two drugs with collateral sensitivity to each other could
      suppress the acquisition of resistance to both drugs. Furthermore, we found that
      the combinatorial use of enoxacin, a DNA replication inhibitor, with
      Chloramphenicol can accelerate acquisition of resistance to Chloramphenicol.
      Genome resequencing analyses of the evolved strains suggested that the
      acceleration of resistance acquisition was caused by an increase of mutation
      frequency when enoxacin was added. CONCLUSIONS: Integration of laboratory
      evolution and whole-genome sequencing enabled us to characterize the development
      of resistance in bacteria under combination therapy. These results provide a
      basis for rational selection of antibiotic combinations that suppress resistance
      development effectively.

PMID- 28446155
TI  - Erratum to: Higher serum betatrophin level in type 2 diabetes subjects is
      associated with urinary albumin excretion and renal function.

PMID- 28446154
TI  - Effects of escitalopram and paroxetine on mTORC1 signaling in the rat hippocampus
      under chronic restraint stress.
AB  - BACKGROUND: Recent studies have suggested that the activation of mammalian target
      of rapamycin (mTOR) signaling may be related to antidepressant action. Therefore,
      the present study evaluated whether antidepressant drugs would exert differential
      effects on mTOR signaling in the rat hippocampus under conditions of chronic
      restraint stress. Male Sprague-Dawley rats were subjected to restraint stress for
      6 h/days for 21 days with either escitalopram (10 mg/kg) or paroxetine (10 mg/kg)
      administered after the chronic stress procedure. Western blot analyses were used
      to assess changes in the levels of phospho-Ser2448-mTOR, phospho-Thr37/46-4E-BP
      1, phospho-Thr389-p70S6 K, phospho-Ser422-eIF4B, phospho-Ser240/244-S6, phospho
      Ser473-Akt, and phospho-Thr202/Tyr204-ERK in the hippocampus. RESULTS: Chronic
      restraint stress significantly decreased the levels of phospho-mTOR complex 1
      (mTORC1), phospho-4E-BP-1, phospho-p70S6 K, phospho-eIF4B, phospho-S6, phospho
      Akt, and phospho-ERK (p < 0.05); the administration of escitalopram and
      paroxetine increased the levels of all these proteins (p < 0.05 or 0.01).
      Additionally, chronic restraint stress reduced phospho-mTORC1 signaling
      activities in general, while escitalopram and paroxetine prevented these changes
      in phospho-mTORC1 signaling activities. CONCLUSION: These findings provide
      further data that contribute to understanding the possible relationships among
      mTOR activity, stress, and antidepressant drugs.

PMID- 28446156
TI  - Conjunctival granuloma with necrosis associated with exposed suture in upper
      double lid masquerading as ocular surface squamous neoplasia: a case report.
AB  - BACKGROUND: This study reports two cases of conjunctival granuloma with necrosis
      caused by an exposed suture in the upper palpebral conjunctiva masquerading as
      ocular surface squamous neoplasia. CASE PRESENTATION: Two patients presented with
      chronic conjunctival ulcerative and granulomatous lesions on the superior bulbar
      conjunctiva that repeatedly recurred after the mass was removed. The pathologic
      findings revealed the absence of malignant cells and presence of many
      lymphocytes, plasma cells, and histiocytes. There was no evidence of acid-fast
      bacilli or fungal organisms. When a past history of blepharoplasty was
      established, microscopic examination revealed occult exposed suture tips. After
      the sutures were removed, the granuloma with necrosis was resolved within a
      month. CONCLUSION: For all conjunctival lesions in the superior bulbar
      conjunctiva, a thorough examination of the ocular adnexae which includes eyelid
      eversion should be performed. There should be a suspicion of foreign body or
      exposed suture material especially when there is a non-healing ulcer.

PMID- 28446158
TI  - Parameter inference for stochastic single-cell dynamics from lineage tree data.
AB  - BACKGROUND: With the advance of experimental techniques such as time-lapse
      fluorescence microscopy, the availability of single-cell trajectory data has
      vastly increased, and so has the demand for computational methods suitable for
      parameter inference with this type of data. Most of currently available methods
      treat single-cell trajectories independently, ignoring the mother-daughter
      relationships and the information provided by the population structure. However,
      this information is essential if a process of interest happens at cell division,
      or if it evolves slowly compared to the duration of the cell cycle. RESULTS: In
      this work, we propose a Bayesian framework for parameter inference on single-cell
      time-lapse data from lineage trees. Our method relies on a combination of
      Sequential Monte Carlo for approximating the parameter likelihood function and
      Markov Chain Monte Carlo for parameter exploration. We demonstrate our inference
      framework on two simple examples in which the lineage tree information is
      crucial: one in which the cell phenotype can only switch at cell division and
      another where the cell state fluctuates slowly over timescales that extend well
      beyond the cell-cycle duration. CONCLUSION: There exist several examples of
      biological processes, such as stem cell fate decisions or epigenetically
      controlled phase variation in bacteria, where the cell ancestry is expected to
      contain important information about the underlying system dynamics. Parameter
      inference methods that discard this information are expected to perform poorly
      for such type of processes. Our method provides a simple and computationally
      efficient way to take into account single-cell lineage tree data for the purpose
      of parameter inference and serves as a starting point for the development of more
      sophisticated and powerful approaches in the future.

PMID- 28446157
TI  - Natural products isolated from Tetragonula carbonaria cerumen modulate free
      radical-scavenging and 5-lipoxygenase activities in vitro.
AB  - BACKGROUND: Propolis and cerumen are plant-derived products found in honeybees
      and stingless bees, respectively. Although propolis is an ancient folk medicine,
      the bioactivities of cerumen obtained from Australian native stingless bees
      (Tetragonula carbonaria) have not been widely studied. Therefore, we investigated
      selected anti-oxidant and anti-inflammatory properties of T. carbonaria cerumen.
      METHODS: A methanolic extract was prepared from the combined cerumen of 40 T.
      carbonaria hives, and HPLC was used to screen for chemical constituents that
      scavenged 2,2-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The ability
      of cerumen extracts to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and to
      interfere with leukotriene B4 (LTB4) production in ionomycin-stimulated human
      neutrophils was also examined. RESULTS: The extract dose-dependently scavenged
      DPPH (EC50 = 27.0 +/- 2.3 MUg/mL); and inhibited the 5-lipoxygenase (5-LOX)
      mediated oxidation of linoleic acid (IC50 = 67.1 +/- 9.6 MUg/mL). Pre-treatment
      of isolated human neutrophils with the methanolic cerumen extract additionally
      inhibited the ionomycin-stimulated production of LTB4 from these cells (IC50 =
      13.3 +/- 5.3 MUg/mL). Following multi-solvent extraction, the free radical
      scavenging and 5-LOX-inhibiting activities of the initial cerumen extract were
      retained in a polar, methanol-water extract, which contained gallic acid and a
      range of flavonone and phenolic natural products. CONCLUSIONS: The findings
      identify free radical scavenging activity, and interference by extracts of T.
      carbonaria cerumen in 5-LOX-LTB4 signaling. Further investigation is needed to
      determine whether the extracts will provide therapeutic benefits for medical
      conditions in which oxidative stress and inflammation are implicated, including
      cardiovascular disease and impaired wound healing.

PMID- 28446159
TI  - The quality of Medicaid and Medicare data obtained from CMS and its contractors:
      implications for pharmacoepidemiology.
AB  - BACKGROUND: Administrative claims of United States Centers for Medicare and
      Medicaid Services (CMS) beneficiaries have long been used in non-experimental
      research. While CMS performs in-house checks of these claims, little is known of
      their quality for conducting pharmacoepidemiologic research. We performed
      exploratory analyses of the quality of Medicaid and Medicare data obtained from
      CMS and its contractors. METHODS: Our study population consisted of Medicaid
      beneficiaries (with and without dual coverage by Medicare) from California,
      Florida, New York, Ohio, and Pennsylvania. We obtained and compiled 1999-2011
      data from these state Medicaid programs (constituting about 38% of nationwide
      Medicaid enrollment), together with corresponding national Medicare data for
      dually-enrolled beneficiaries. This descriptive study examined longitudinal
      patterns in: dispensed prescriptions by state, by quarter; and inpatient
      hospitalizations by federal benefit, state, and age group. We further examined
      discrepancies between demographic characteristics and disease states, in
      particular frequencies of pregnancy complications among men and women beyond
      childbearing age, and prostate cancers among women. RESULTS: Dispensed
      prescriptions generally increased steadily and consistently over time, suggesting
      that these claims may be complete. A commercially-available National Drug Code
      lookup database was able to identify the dispensed drug for 95.2-99.4% of these
      claims. Because of co-coverage by Medicare, Medicaid data appeared to miss a
      substantial number of hospitalizations among beneficiaries >= 45 years of age.
      Pregnancy complication diagnoses were rare in males and in females >= 60 years of
      age, and prostate cancer diagnoses were rare in females. CONCLUSIONS: CMS claims
      from five large states obtained directly from CMS and its contractors appeared to
      be of high quality. Researchers using Medicaid data to study hospital outcomes
      should obtain supplemental Medicare data on dual enrollees, even for non-elders.
      TRIAL REGISTRATION: Not applicable.

PMID- 28446161
TI  - Erratum to: Assessing the reporting of categorised quantitative variables in
      observational epidemiological studies.

PMID- 28446160
TI  - Hydro-ethanolic leaf extract of Ziziphus abyssinica Hochst Ex A. Rich
      (Rhamnaceae) exhibits anti-nociceptive effects in murine models.
AB  - BACKGROUND: Despite substantial advances in pain research and treatment, millions
      of people continue to suffer from pain and this has been attributed mainly to the
      unavailability of effective and safer analgesics. The use of plants as medicines
      is still widespread and plants constitute a large source of novel phytocompounds
      that might become leads for the discovery of newer, effective and safer
      alternatives. Various parts of Ziziphus abyssinica have been used in folk
      medicine in several African countries as painkillers. However, there is no report
      on the possible anti-nociceptive effects of this plant especially the leaves,
      hence the need for this current study. METHODS: The possible anti-nociceptive
      activity of hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) was
      assessed in rodents using chemical (acetic acid, formalin and glutamate), thermal
      (tail-immersion test) and mechanical/inflammatory (carrageenan) models of
      nociception. RESULTS: EthE (30-300 mg/kg, p.o.) dose-dependently and
      significantly inhibited chemical-induced nociception with a maximum inhibition of
      86.29 +/- 2.27%, 76.34 +/- 5.67%, 84.97 +/- 5.35%, and 82.81 +/- 5.97%
      respectively for acetic acid, formalin (phase 1), formalin (phase 2) and
      glutamate tests at its highest dose. EthE also dose-dependently and significantly
      increased reaction times in both tail-immersion and carrageenan-induced
      hypernociceptive tests. The activities of the extract in the various models were
      comparable with the effect of morphine hydrochloride and diclofenac sodium used
      as standard analgesic drugs. CONCLUSION: Oral administration of hydro-ethanolic
      leaf extract of Ziziphus abyssinica ameliorates nocifensive behaviours associated
      with chemical-, thermal- and mechanical/inflammatory - induced nociceptive pain.

PMID- 28446162
TI  - Prevalence and risk factors for non-alcoholic fatty liver in children and youth
      with obesity.
AB  - BACKGROUND: Non- Alcoholic Fatty Liver (NAFL) is a spectrum of liver diseases
      (LD) that ranges from benign fatty infiltration of the liver to cirrhosis and
      hepatic failure. Hepatic ultrasound (US) and serum alanine aminotransferase (ALT)
      are often used as markers of NAFL. Our aim is to describe prevalence of NAFL and
      associated findings on ultrasound (US) and biochemical parameters in a population
      of children and adolescents with obesity at the Children's Hospital of Eastern
      Ontario. METHODS: Children with Obesity (BMI >95th percentile) ages 8-17 years
      presenting to the Endocrinology and Gastroenterology clinics, without underlying
      LD were prospectively recruited from 2009 to 2012. Fasting lipid profile, HOMA
      IR) and serum adiponectin levels were measured. NAFL was defined as ALT > 25 and
      >22 IU/mL (males and females respectively) and/or evidence of fatty infiltration
      by US. Logistic regression was performed to assess associations. RESULTS: 97
      children with obesity included in the study (Male 43%). Mean age was 12.9 +/- 3.2
      years (84% were older than 10 y). Mean BMI-Z score was 3.8 +/- 1.4. NAFL was
      identified in 85%(82/97) of participants. ALT was elevated in 61% of patients.
      Median triglyceride (TG) level was higher in children with NAFL(1.5 +/- 0.9 vs.
      1.1 +/- 0.5 mmol/L, p = 0.01). Total cholesterol, HDL, LDL and Non HDL
      cholesterol were similar in both groups(p = 0.63, p = 0.98, p = 0.72 and p = 0.37
      respectively). HOMA IR was >=3.16 in 53% of children(55% in those with NAFL and
      40% in those without NAFL). Median serum adiponectin was 11.2 MUg/ml(IQR 7.3
      18.3) in children with NAFL vs. 16.1 MUg/ml(IQR 9.0-21.9) in those without NAFL(p
      = 0.23). Liver US was reported as normal in 30%, mild fatty infiltration in 38%,
      moderate in 20% and severe in 12%. TG were significantly higher(1.5 mmol/L vs.
      1.0 mmol/L, p < 0.01) and HDL-C was lower(1.0 mmol/L vs. 1.1 mmol/L, p = 0.05) in
      children with moderate and severe NAFL by US. BMI-Z score, HOMA IR, serum
      adiponectin and HDL levels were not associated with NAFL, however TG were
      significantly associated(OR = 3.22 (95% CI: 1.01-10.25, p = 0.04)). CONCLUSION:
      NAFL is highly prevalent in obese children and youth. Elevated TG levels are
      associated with NAFL; these findings may serve as a noninvasive screening tool to
      help clinicians identify children with obesity needing liver biopsy and/or more
      aggressive therapeutic interventions.

PMID- 28446163
TI  - Exploratory analysis of the neutrophil to lymphocyte ratio in patients with
      pulmonary arterial hypertension.
AB  - BACKGROUND: Chronic inflammation emerges as a feature of the pathogenesis of
      pulmonary arterial hypertension (PAH) in experimental models. Alterations of
      circulating cell subsets have been observed in patients with PAH. We aimed to
      assess associations of the white blood cell count with disease severity and
      outcome in patients with PAH. METHODS: The total and differential white blood
      cell count was related to functional parameters, pulmonary hemodynamics and
      transplantation-free survival in 77 patients with PAH in an observational single
      center study. RESULTS: An increased neutrophil/lymphocyte ratio was associated
      with poor World Health Organization functional class and shorter 6-minute walking
      distance, as well as with elevated right atrial pressure and high level of N
      terminal prohormone of brain natriuretic peptide. During a median follow-up
      period of 31 months (range 16-56) 23 patients died and 2 patients were referred
      to lung transplantation. Using uni- and subsequent bivariate Cox proportional
      hazards analyses an increased neutrophil/lymphocyte ratio was associated with
      unfavorable transplantation-free survival independent of hemodynamic parameters
      and C-reactive protein. The prognostic implication sustained in subsets of
      patients with incident PAH and in the absence of cardiovascular risk factors.
      CONCLUSIONS: The results of this analysis indicate that a neutrophilic
      inflammation may be associated with clinical deterioration and poor outcome in
      patients with PAH. Assessing the composition of the differential white blood cell
      count may render prognostic information and could represent a step towards
      incorporating an inflammatory marker into the clinical management of patients
      with PAH.

PMID- 28446164
TI  - Core information sets for informed consent to surgical interventions: baseline
      information of importance to patients and clinicians.
AB  - BACKGROUND: Consent remains a crucial, yet challenging, cornerstone of clinical
      practice. The ethical, legal and professional understandings of this construct
      have evolved away from a doctor-centred act to a patient-centred process that
      encompasses the patient's values, beliefs and goals. This alignment of consent
      with the philosophy of shared decision-making was affirmed in a recent high
      profile Supreme Court ruling in England. The communication of information is
      central to this model of health care delivery but it can be difficult for doctors
      to gauge the information needs of the individual patient. The aim of this paper
      is to describe 'core information sets' which are defined as a minimum set of
      consensus-derived information about a given procedure to be discussed with all
      patients. Importantly, they are intended to catalyse discussion of subjective
      importance to individuals. MAIN BODY: The model described in this paper applies
      health services research and Delphi consensus-building methods to an idea
      orginally proposed 30 years ago. The hypothesis is that, first, large amounts of
      potentially-important information are distilled down to discrete information
      domains. These are then, secondly, rated by key stakeholders in multiple
      iterations, so that core information of agreed importance can be defined. We
      argue that this scientific approach is key to identifying information important
      to all stakeholders, which may otherwise be communicated poorly or omitted from
      discussions entirely. Our methods apply systematic review, qualitative, survey
      and consensus-building techniques to define this 'core information'. We propose
      that such information addresses the 'reasonable patient' standard for information
      disclosure but, more importantly, can serve as a spring board for high-value
      discussion of importance to the individual patient. CONCLUSION: The application
      of established research methods can define information of core importance to
      informed consent. Further work will establish how best to incorporate this model
      in routine practice.

PMID- 28446165
TI  - Knowledge-exchange in the Pacific: outcomes of the TROPIC (translational research
      for obesity prevention in communities) project.
AB  - BACKGROUND: The Pacific TROPIC (Translational Research for Obesity Prevention in
      Communities) project aimed to design, implement and evaluate a knowledge-broking
      approach to evidence-informed policy making to address obesity in Fiji. This
      paper reports on the quantitative evaluation of the knowledge-broking
      intervention through assessment of participants' perceptions of evidence use and
      development of policy/advocacy briefs. METHODS: Selected staff from six
      organizations - four government Ministries and two nongovernment organizations
      (NGOs) - participated in the project. The intervention comprised workshops and
      supported development of policy/advocacy briefs. Workshops addressed obesity and
      policy cycles and developing participants' skills in accessing, assessing,
      adapting and applying relevant evidence. A knowledge-broking team supported
      participants individually and/or in small groups to develop evidence-informed
      policy/advocacy briefs. A questionnaire survey that included workplace and
      demographic items and the self-assessment tool "Is Research Working for You?"
      (IRWFY) was administered pre- and post-intervention. RESULTS: Forty nine
      individuals (55% female, 69% 21-40 years, 69% middle-senior managers)
      participated in the study. The duration and level of participant engagement with
      the intervention activities varied - just over half participated for 10+ months,
      just under half attended most workshops and approximately one third produced one
      or more policy briefs. There were few reliable changes on the IRWFY scales
      following the intervention; while positive changes were found on several scales,
      these effects were small (d < .2) and only one individual scale (assess) was
      statistically significant (p < .05). Follow up (N = 1) analyses of individual
      level change indicated that while 63% of participants reported increased research
      utilization post-intervention, this proportion was not different to chance
      levels. Similar analysis using scores aggregated by organization also revealed no
      organizational-level change post-intervention. CONCLUSIONS: This study
      empirically evaluated a knowledge-broking program that aimed to extend evidence
      informed policy making skills and development of a suite of national policy
      briefs designed to increase the enactment of obesity-related policies. The
      findings failed to indicate reliable improvements in research utilization at
      either the individual or organizational level. Factors associated with fidelity
      and intervention dose as well as challenges related to organizational support and
      the measurement of research utilization, are discussed and recommendations for
      future research presented.

PMID- 28446166
TI  - Change in renin, cardiovascular and inflammatory markers over three years in a
      black and white population: the SABPA study.
AB  - BACKGROUND: To investigate if percentage change (%?) in renin over a 3 year
      follow-up is associated with %? in cardiovascular and inflammatory markers in a
      low renin bi-ethnic group. METHODS: Blood pressure, active renin, C-reactive
      protein and interleukin-6 levels of 73 black and 81 white teachers were measured
      at baseline and after 3 years. RESULTS: In the black group, %? renin was
      inversely associated with %? systolic blood pressure (beta = -0.27; p = 0.011).
      In the white group %? renin was inversely associated with %?interleukin-6 (beta =
      -0.24; p = 0.005). CONCLUSIONS: These prospective results indicate that a
      decrease in renin over time is associated with an increase in blood pressure in a
      low renin black South African cohort.

PMID- 28446167
TI  - Evaluation of biometry and corneal astigmatism in cataract surgery patients from
      Central China.
AB  - BACKGROUND: To evaluate the distribution of biometric parameters and corneal
      astigmatism using the IOLMaster device before phacoemulsification in cataract
      patients in Central China. METHODS: Consecutive cataract patients were recruited
      at the Central Hospital of Wuhan between January 2015 and June 2016. Ocular axial
      length (AL), keratometry values, anterior chamber depth (ACD) and horizontal
      corneal diameter (white to white [WTW]) of each cataract-affected eye were
      measured with the IOLMaster device. RESULTS: The study evaluated 3209 eyes of
      2821 cataract patients. The mean AL, ACD, and WTW were 24.38 +/- 2.47 mm, 3.15 +/
      0.48 mm, and 11.63 +/- 0.43 mm, respectively. Corneal astigmatism of 0.51-1.00
      diopters (D) was the most common range of values (34.96%). A total of 10.56%
      patients exhibited a corneal astigmatism greater than 2.0 D. The flat and steep
      keratometry values gradually increased with age. The mean ACD and WTW showed
      increasing trends as the AL increased (P < 0.001). When the AL was shorter than
      26.0 mm, the keratometry decreased as AL increased. The against-the-rule (ATR)
      astigmatism proportion increased with age and the with-the-rule (WTR) astigmatism
      proportion decreased with age. CONCLUSIONS: The profile of ocular biometric data
      and corneal astigmatism may help ophthalmologists improve their surgical
      procedures and make an appropriate IOL choice to gain a high quality of
      postoperative vision.

PMID- 28446168
TI  - Plasma matrix metalloproteinases are associated with incident cardiovascular
      disease and all-cause mortality in patients with type 1 diabetes: a 12-year
      follow-up study.
AB  - BACKGROUND: Altered regulation of extracellular matrix remodeling by matrix
      metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may
      contribute to vascular complications in type 1 diabetes. We investigated
      associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular
      events and all-cause mortality in type 1 diabetic patients. METHODS: We
      prospectively followed 337 type 1 diabetic patients [mean age 41.4 years (9.6),
      39% female], 170 with and 167 without diabetic nephropathy, with median follow-up
      of 12.3 years. Survival analyses were applied to investigate differences in
      plasma MMP-1, -2, -3, -9, -10, and TIMP-1-levels in patients with and without a
      cardiovascular event and in those who died vs survivors. All analyses were
      adjusted for age, sex, duration of diabetes, HbA1c, nephropathy and for other
      conventional cardiovascular risk factors. RESULTS: After adjustment for potential
      confounders, higher MMP-2 plasma levels were significantly associated with higher
      incidence of cardiovascular events [HR 1.49 (95% CI 1.11; 1.99)], and higher
      plasma levels of MMP-1 [1.38 (1.07; 1.78)], MMP-2 [1.60 (1.19; 2.15)] and MMP-3
      [1.39 (1.05; 1.85)] were associated with all-cause mortality. All associations
      were independent of low-grade inflammation and endothelial dysfunction as
      estimated by plasma markers. Associations between MMP-2 and cardiovascular events
      and between MMP-3 and mortality were attenuated after further adjustment for eGFR
      and changes in eGFR. CONCLUSIONS: Higher levels of MMP-2 are associated with CVD
      and higher MMP-1, -2 and -3 with all-cause mortality. In addition, associations
      between MMP-2 and CVD, and MMP-3 and mortality were attenuated after adjustment
      for eGFR while both MMPs were associated with eGFR decline, indicating a possible
      mediating role of eGFR.

PMID- 28446169
TI  - The relative importance of large problems far away versus small problems closer
      to home: insights into limiting the spread of antimicrobial resistance in
      England.
AB  - BACKGROUND: To combat the spread of antimicrobial resistance (AMR), hospitals are
      advised to screen high-risk patients for carriage of antibiotic-resistant
      bacteria on admission. This often includes patients previously admitted to
      hospitals with a high AMR prevalence. However, the ability of such a strategy to
      identify introductions (and hence prevent onward transmission) is unclear, as it
      depends on AMR prevalence in each hospital, the number of patients moving between
      hospitals, and the number of hospitals considered 'high risk'. METHODS: We
      tracked patient movements using data from the National Health Service of England
      Hospital Episode Statistics and estimated differences in regional AMR prevalences
      using, as an exemplar, data collected through the national reference laboratory
      service of Public Health England on carbapenemase-producing Enterobacteriaceae
      (CPE) from 2008 to 2014. Combining these datasets, we calculated expected CPE
      introductions into hospitals from across the hospital network to assess the
      effectiveness of admission screening based on defining high-prevalence hospitals
      as high risk. RESULTS: Based on numbers of exchanged patients, the English
      hospital network can be divided into 14 referral regions. England saw a sharp
      increase in numbers of CPE isolates referred to the national reference laboratory
      over 7 years, from 26 isolates in 2008 to 1649 in 2014. Large regional
      differences in numbers of confirmed CPE isolates overlapped with regional
      structuring of patient movements between hospitals. However, despite these large
      differences in prevalence between regions, we estimated that hospitals received
      only a small proportion (1.8%) of CPE-colonised patients from hospitals outside
      their own region, which decreased over time. CONCLUSIONS: In contrast to the
      focus on import screening based on assigning a few hospitals as 'high risk',
      patient transfers between hospitals with small AMR problems in the same region
      often pose a larger absolute threat than patient transfers from hospitals in
      other regions with large problems, even if the prevalence in other regions is
      orders of magnitude higher. Because the difference in numbers of exchanged
      patients, between and within regions, was mostly larger than the difference in
      CPE prevalence, it would be more effective for hospitals to focus on their own
      populations or region to inform control efforts rather than focussing on problems
      elsewhere.

PMID- 28446170
TI  - Latin America validation of FACED score in patients with bronchiectasis: an
      analysis of six cohorts.
AB  - BACKGROUND: The FACED score is an easy-to-use multidimensional grading system
      that has demonstrated an excellent prognostic value for mortality in patients
      with bronchiectasis. A Spanish group developed the score but no multicenter
      international validation has yet been published. METHODS: Retrospective and
      multicenter study conducted in six historical cohorts of patients from Latin
      America including 651 patients with bronchiectasis. Clinical, microbiological,
      functional, and radiological variables were collected, following the same
      criteria used in the original FACED score study. The vital status of all patients
      was determined in the fifth year of follow-up. The area under ROC curve (AUC-ROC)
      was used to calculate the predictive power of the FACED score for all-cause and
      respiratory deaths and both number and severity of exacerbations. The
      discriminatory power to divide patients into three groups of increasing severity
      was also analyzed. RESULTS: Mean (SD) age of 48.2 (16), 32.9% of males. The mean
      FACED score was 2.35 (1.68). During the follow up, 95 patients (14.6%) died (66%
      from respiratory causes). The AUC ROC to predict all-cause and respiratory
      mortality were 0.81 (95% CI: 0.77 to 0.85) 0.84 (95% CI: 0.80 to 0.88)
      respectively, and 0.82 (95% CI: 078-0.87) for at least one hospitalization per
      year. The division into three score groups separated bronchiectasis into distinct
      mortality groups (mild: 3.7%; moderate: 20.7% and severe: 48.5% mortality; p <
      0.001). CONCLUSIONS: The FACED score was confirmed as an excellent predictor of
      all-cause and respiratory mortality and severe exacerbations, as well as having
      excellent discriminative capacity for different degrees of severity in various
      bronchiectasis populations.

PMID- 28446171
TI  - Oral immune priming with Bacillus thuringiensis induces a shift in the gene
      expression of Tribolium castaneum larvae.
AB  - BACKGROUND: The phenomenon of immune priming, i.e. enhanced protection following
      a secondary exposure to a pathogen, has now been demonstrated in a wide range of
      invertebrate species. Despite accumulating phenotypic evidence, knowledge of its
      mechanistic underpinnings is currently very limited. Here we used the system of
      the red flour beetle, Tribolium castaneum and the insect pathogen Bacillus
      thuringiensis (Bt) to further our molecular understanding of the oral immune
      priming phenomenon. We addressed how ingestion of bacterial cues (derived from
      spore supernatants) of an orally pathogenic and non-pathogenic Bt strain affects
      gene expression upon later challenge exposure, using a whole-transcriptome
      sequencing approach. RESULTS: Whereas gene expression of individuals primed with
      the orally non-pathogenic strain showed minor changes to controls, we found that
      priming with the pathogenic strain induced regulation of a large set of distinct
      genes, many of which are known immune candidates. Intriguingly, the immune
      repertoire activated upon priming and subsequent challenge qualitatively differed
      from the one mounted upon infection with Bt without previous priming. Moreover, a
      large subset of priming-specific genes showed an inverse regulation compared to
      their regulation upon challenge only. CONCLUSIONS: Our data demonstrate that gene
      expression upon infection is strongly affected by previous immune priming. We
      hypothesise that this shift in gene expression indicates activation of a more
      targeted and efficient response towards a previously encountered pathogen, in
      anticipation of potential secondary encounter.

PMID- 28446172
TI  - Clinical characteristics of eosinophilic COPD versus COPD patients with a history
      of asthma.
AB  - Eosinophilic COPD appears to be a distinct patient subgroup with an increased
      corticosteroid response. Eosinophilic COPD has been labelled as part of the
      asthma COPD overlap syndrome (ACOS). We compared the clinical characteristics of
      eosinophilic COPD patients (without any clinical history of asthma) and COPD
      patients with a childhood history of asthma. COPD patients with asthma were
      characterised by more allergies and more exacerbations, but less eosinophilic
      inflammation. While terms such as "ACOS" are used to "lump" patients together, we
      report distinct differences between eosinophilic COPD and COPD patients with
      asthma, and propose that these groups should be split rather than lumped.

PMID- 28446173
TI  - Impact of the Ebola outbreak on routine immunization in western area, Sierra
      Leone - a field survey from an Ebola epidemic area.
AB  - BACKGROUND: Since March 2014, the Ebola Virus Disease (EVD) outbreak in West
      Africa disrupted health care systems - especially in Guinea, Liberia and Sierra
      Leone - with a consequential stress on the area's routine immunization programs.
      To address perceived decreased vaccination coverage, Sierra Leone conducted a
      catch-up vaccination campaign during 24-27 April 2015. We conducted a vaccination
      coverage survey and report coverage estimates surrounding the time of the EVD
      outbreak and the catch-up campaign. METHODS: We selected 3 villages from each of
      3 communities and obtained dates of birth and dates of vaccination with measles
      vaccine (MV) and the 3rd dose of Pentavalent vaccine (Pentavalent3) of all
      children under 4 years of age in the 9 selected villages. Vaccination data were
      obtained from parent-held health cards. We calculated the children's MV and
      Pentavalent3 coverage rates at 3 time points, 1 August 2014, 1 April 2015, and 1
      May 2015, representing coverage rates before the EVD outbreak, during the EVD
      outbreak, and after the Maternal and Child Health Week (MCHW) catch-up campaign.
      RESULTS: The final sample size was 168 children. MV coverage among age-eligible
      children was 71.3% (95% confidence interval [CI]: 62.1% - 80.4%) and 45.7% (95%
      CI: 29.2% - 62.2%) before and during the outbreak of EVD, respectively, and was
      56.8% (95% CI: 40.8% - 72.7%) after the campaign. Pentavalent3 coverage among age
      eligible children was 79.8% (95% CI: 72.6% - 87.0%) and 40.0% (95% CI: 22.5% -
      57.5%) before and during the outbreak of EVD, and was 56.4% (95% CI: 39.1% -
      73.4%) after the campaign. CONCLUSIONS: Coverage levels of MV and Pentavalent3
      were low before the EVD outbreak and decreased further during the outbreak.
      Although the MCHW catch-up campaign increased coverage levels, coverage remained
      below pre-outbreak levels. High-quality supplementary immunization activities
      should be conducted and routine immunization should be strengthened to address
      gaps in immunity among children in this EVD-affected area.

PMID- 28446174
TI  - A scalable metabolite supplementation strategy against antibiotic resistant
      pathogen Chromobacterium violaceum induced by NAD+/NADH+ imbalance.
AB  - BACKGROUND: The leading edge of the global problem of antibiotic resistance
      necessitates novel therapeutic strategies. This study develops a novel systems
      biology driven approach for killing antibiotic resistant pathogens using benign
      metabolites. RESULTS: Controlled laboratory evolutions established
      chloramphenicol and streptomycin resistant pathogens of Chromobacterium. These
      resistant pathogens showed higher growth rates and required higher lethal doses
      of antibiotic. Growth and viability testing identified malate, maleate,
      succinate, pyruvate and oxoadipate as resensitising agents for antibiotic
      therapy. Resistant genes were catalogued through whole genome sequencing.
      Intracellular metabolomic profiling identified violacein as a potential biomarker
      for resistance. The temporal variance of metabolites captured the linearized
      dynamics around the steady state and correlated to growth rate. A constraints
      based flux balance model of the core metabolism was used to predict the metabolic
      basis of antibiotic susceptibility and resistance. CONCLUSIONS: The model
      predicts electron imbalance and skewed NAD/NADH ratios as a result of antibiotics
      - chloramphenicol and streptomycin. The resistant pathogen rewired its metabolic
      networks to compensate for disruption of redox homeostasis. We foresee the
      utility of such scalable workflows in identifying metabolites for clinical
      isolates as inevitable solutions to mitigate antibiotic resistance.

PMID- 28446175
TI  - Bacillus pumilus KatX2 confers enhanced hydrogen peroxide resistance to a
      Bacillus subtilis PkatA::katX2 mutant strain.
AB  - BACKGROUND: Bacillus pumilus cells exhibit a significantly higher resistance to
      hydrogen peroxide compared to closely related Bacilli like Bacillus subtilis.
      RESULTS: In this study we analyzed features of the catalase KatX2 of B. pumilus
      as one of the most important parts of the cellular response to hydrogen peroxide.
      KatX2, the vegetative catalase expressed in B. pumilus, was compared to the
      vegetative catalase KatA of B. subtilis. Data of our study demonstrate that B.
      pumilus can degrade toxic concentrations of hydrogen peroxide faster than B.
      subtilis. By replacing B. subtilis katA gene by katX2 we could significantly
      enhance its resistance to H2O2 and its potential to eliminate this toxic
      compound. Mutant cells showed a 1.5- to 2-fold higher survival to toxic
      concentrations of hydrogen peroxide compared to wild type cells. Furthermore, we
      found reversible but also irreversible oxidations of the KatX2 protein which, in
      contrast to KatA, contains several cysteine residues. CONCLUSIONS: Our study
      indicates that the catalase KatX2 plays a major role in the increased resistance
      of B. pumilus to oxidative stress caused by hydrogen peroxide. Resistance to
      hydrogen peroxide of other Bacilli can be enhanced by exchanging the native
      catalase in the cells with katX2.

PMID- 28446176
TI  - Health care providers' perspectives regarding the use of chlorhexidine gel for
      cord care in neonates in rural Kenya: implications for scale-up.
AB  - BACKGROUND: This paper explores the perspectives of health care providers
      regarding the use of 7.1% Chlorhexidine Digluconate (CHX) gel that releases 4%
      chlorhexidine for newborn umbilical cord care under a managed access program
      (MAP) implemented in Bungoma County of Kenya. Understanding the perspectives of
      providers regarding CHX is important since they play a key role in the health
      system and the fact that their views could be influenced by prior beliefs and
      inconsistent practices regarding umbilical cord care. METHODS: Data are from in
      depth interviews conducted between April and June 2016 with 39 service providers
      from 21 facilities that participated in the program. The data were transcribed,
      typed in Word and analyzed for content. Analysis entailed identifying recurring
      themes based on the interview guides. RESULTS: Use of CHX gel for cord care in
      neonates was acceptable to the health care providers, with all of them supporting
      scaling up its use throughout the country. Their views were largely influenced by
      positive outcomes of the medication including fast healing of the cord as
      reported by mothers, minimal side effects, reduced newborn infections based on
      what their records showed and mothers' reports, ease of use that made it simple
      for them to counsel mothers on how to apply it, positive feedback from mothers
      which demonstrated satisfaction with the medication, and general acceptance of
      the medication by the community. They further noted that successful scale-up of
      the medication required community sensitization, adequate follow-up mechanisms to
      ensure mothers use the medication correctly, addressing issues of staffing levels
      and staff training, developing guidelines and protocols for provision of the
      medication, adopting appropriate service delivery approaches to ensure all groups
      of mothers are reached, and ensuring constant supply of the medication.
      CONCLUSION: Use of CHX gel for cord care in neonates is likely to be acceptable
      to health care workers in settings with high prevalence of neonatal morbidity and
      mortality arising from cord infections. In scaling up the use of the medication
      in such settings, some of the health systems requirements for successful roll-out
      can be addressed by programs while others are likely to be a persistent
      challenge.

PMID- 28446177
TI  - The susceptibility to fosfomycin of Gram-negative bacteria isolates from urinary
      tract infection in the Czech Republic: data from a unicentric study.
AB  - BACKGROUND: Against a background of rapid increase of beta-lactamase-producing or
      multi-resistant pathogenic bacteria and the resulting lack of effective
      antibiotic treatment, some older antibiotics have been tested for new therapeutic
      uses. One of these is fosfomycin, to which according to studies these resistant
      bacteria are very sensitive. Our study was designed because there is no data on
      the fosfomycin susceptibility rate in the Czech Republic. METHOD: In this study
      from January 2013 to June 2014 3295 unique isolates of Gram-negative bacteria
      which had caused urinary tract infections were examined. The antibiotic
      susceptibility was measured by disk diffusion test. Both EUCAST and CLSI
      guidelines criteria (for fosfomycin only) were used for the antibiotic
      susceptibility evaluation. RESULTS: The most frequently tested bacterial isolates
      were Escherichia coli (51.3%, n = 1703), Klebsiella pneumoniae (19.4%, n = 643)
      and Proteus spp. (11.8%, n = 392). Among all isolates 29.0% (n = 963) were
      resistant to fluoroquinolones, 11.3% (n = 374) produced extended spectrum beta
      lactamase and 4.2% (n = 141) produced AmpC beta-lactamase. The overall in vitro
      susceptibility was significantly higher for fosfomycin compared to the other
      tested per-oral antibiotics (nitrofurantoin, ampicillin, co-trimoxazole,
      ciprofloxacin and cefuroxime) against all tested Gram-negative rod isolates
      (excluding Morganella morgani and Acinetobacter spp. isolates). Fosfomycin also
      remained highly active against those isolates with extended spectrum beta
      lactamase (ESBL) production (95.8% in Escherichia coli isolates and 85.3% in
      Klebsiella pneumoniae isolates), unlike other tested per-oral antibiotics, which
      showed significant (p < 0.0001) susceptibility decrease. CONCLUSION: We have
      confirmed in the Czech Republic the very high susceptibility to fosfomycin
      trometamol of urinary tract infection pathogens, particularly Gram-negative rods
      including those producing beta-lactamase.

PMID- 28446178
TI  - Inequality in unmet dental care needs among South Korean adults.
AB  - BACKGROUND: The current public health research agenda was to identify the means
      to reduce oral health inequalities internationally. The objectives of this study
      were to provide evidence of inequality in unmet dental needs and to find
      influencing factors attributable to those among South Korean adults. METHODS:
      Pooled cross-sectional data from the fourth Korean National Health and Nutrition
      Examination Survey (2007-2009) on 17,141 Korean adults were used. Demographic
      factors (sex, age, and marital status), socioeconomic factors (education level,
      employment status, and income level), need factors (normative dental needs and
      self-perceived oral health status), and oral health-related factors (the number
      of decayed teeth, the presence of periodontitis, and the number of missing teeth)
      were included. Multiple logistic regression analysis was performed. RESULTS: Of
      South Korean adults, 43.9% had perceived unmet dental needs, with the most common
      reason being financial difficulties. The disparities in unmet dental care needs
      were strongly associated with income level, normative treatment needs, and self
      perceived oral health status. The low-income group, people with normative dental
      treatment needs, and those with perceived poor oral health status were more
      likely to have unmet dental needs. There was considerable inequality in unmet
      dental care needs due to economic reasons according to such socioeconomic factors
      as income and education level. CONCLUSIONS: Public health policies with the
      expansion of dental insurance coverage are needed to reduce inequalities in unmet
      dental care needs and improve the accessibility of dental care services to
      vulnerable groups who are experiencing unmet dental care needs due to
      socioeconomic factors despite having normative and self-perceived needs for
      dental treatment.

PMID- 28446180
TI  - Physical activity when riding an electric assisted bicycle.
AB  - BACKGROUND: The objectives of the present study were to compare time spent
      cycling, exercise intensity, and time spent in moderate- (MPA) and vigorous
      intensity physical activity (VPA) when cycling on an E-bike and a conventional
      bicycle on two "cycling-to-work" routes with differences in topography, defined
      as a hilly and a flat route. METHODS: Eight adults (23-54 years, two women)
      cycled outdoors on a conventional bicycle and an E-bike, on a flat (8.2 km) and a
      hilly (7.1 km) route, resulting in 32 journeys. Duration, elevation, and oxygen
      consumption were recorded using a portable oxygen analyser with GPS. A maximal
      cardiorespiratory fitness test was performed on a cycle ergometer. Resting
      metabolic rate was obtained by indirect calorimetry with a canopy hood. RESULTS:
      The participants spent less time (median (IQR)) cycling on the E-bike compared
      with the conventional bicycle, on both the hilly (18.8 (4.9) vs. 26.3 (6.4)
      minutes) and the flat (20.0 (2.9) vs. 23.8 (1.8) minutes) routes. Lower exercise
      intensity was observed with the E-bike compared with the conventional bicycle,
      both on the hilly (50 (18) vs. 60 (22) % of maximal oxygen uptake) and the flat
      (52 (19) vs. 55 (12) % of maximal oxygen uptake) routes. In both cycling modes,
      most time was spent in MVPA (92-99%). However, fewer minutes were spent in MVPA
      with the E-bike than the conventional bicycle, for both the hilly (26% lower) and
      the flat (17% lower) routes. Cycling on the E-bike also resulted in 35 and 15%
      fewer minutes in vigorous intensity, respectively on the hilly and flat routes.
      CONCLUSION: Cycling on the E-bike resulted in lower trip duration and exercise
      intensity, compared with the conventional bicycle. However, most of the time was
      spent in MVPA. This suggests that changing the commuting mode from car to E-bike
      will significantly increase levels of physical activity while commuting.

PMID- 28446179
TI  - GlyCAM1 negatively regulates monocyte entry into the optic nerve head and
      contributes to radiation-based protection in glaucoma.
AB  - BACKGROUND: We previously reported a profound long-term neuroprotection
      subsequent to a single radiation-therapy in the DBA/2J mouse model of glaucoma.
      This neuroprotection prevents entry of monocyte-like immune cells into the optic
      nerve head during glaucoma. Gene expression studies in radiation-treated mice
      implicated Glycam1 in this protection. Glycam1 encodes a proteoglycan ligand for
      L-selectin and is an excellent candidate to modulate immune cell entry into the
      eye. Here, we experimentally test the hypothesis that radiation-induced over
      expression of Glycam1 is a key component of the neuroprotection. METHODS: We
      generated a null allele of Glycam1 on a DBA/2J background. Gene and protein
      expression of Glycam1, monocyte entry into the optic nerve head, retinal ganglion
      cell death, and axon loss in the optic nerve were assessed. RESULTS: Radiation
      therapy potently inhibits monocyte entry into the optic nerve head and prevents
      retinal ganglion cell death and axon loss. DBA/2J mice carrying a null allele of
      Glycam1 show increased monocyte entry and increased retinal ganglion cell death
      and axon loss following radiation therapy, but the majority of optic nerves were
      still protected by radiation therapy. CONCLUSIONS: Although GlyCAM1 is an L
      selectin ligand, its roles in immunity are not yet fully defined. The current
      study demonstrates a partial role for GlyCAM1 in radiation-mediated protection.
      Furthermore, our results clearly show that GlyCAM1 levels modulate immune cell
      entry from the vasculature into neural tissues. As Glycam1 deficiency has a more
      profound effect on cell entry than on neurodegeneration, further experiments are
      needed to precisely define the role of monocyte entry in DBA/2J glaucoma.
      Nevertheless, GlyCAM1's function as a negative regulator of extravasation may
      lead to novel therapeutic strategies for an array of common conditions involving
      inflammation.

PMID- 28446181
TI  - A Neuromuscular Electrical Stimulation (NMES) and robot hybrid system for multi
      joint coordinated upper limb rehabilitation after stroke.
AB  - BACKGROUND: It is a challenge to reduce the muscular discoordination in the
      paretic upper limb after stroke in the traditional rehabilitation programs.
      METHOD: In this study, a neuromuscular electrical stimulation (NMES) and robot
      hybrid system was developed for multi-joint coordinated upper limb physical
      training. The system could assist the elbow, wrist and fingers to conduct arm
      reaching out, hand opening/grasping and arm withdrawing by tracking an indicative
      moving cursor on the screen of a computer, with the support from the joint motors
      and electrical stimulations on target muscles, under the voluntary intention
      control by electromyography (EMG). Subjects with chronic stroke (n = 11) were
      recruited for the investigation on the assistive capability of the NMES-robot and
      the evaluation of the rehabilitation effectiveness through a 20-session device
      assisted upper limb training. RESULTS: In the evaluation, the movement accuracy
      measured by the root mean squared error (RMSE) during the tracking was
      significantly improved with the support from both the robot and NMES, in
      comparison with those without the assistance from the system (P < 0.05). The
      intra-joint and inter-joint muscular co-contractions measured by EMG were
      significantly released when the NMES was applied to the agonist muscles in the
      different phases of the limb motion (P < 0.05). After the physical training,
      significant improvements (P < 0.05) were captured by the clinical scores, i.e.,
      Modified Ashworth Score (MAS, the elbow and the wrist), Fugl-Meyer Assessment
      (FMA), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT).
      CONCLUSIONS: The EMG-driven NMES-robotic system could improve the muscular
      coordination at the elbow, wrist and fingers. TRIAL REGISTRATION:
      ClinicalTrials.gov. NCT02117089 ; date of registration: April 10, 2014.

PMID- 28446182
TI  - Improving preimplantation genetic diagnosis (PGD) reliability by selection of
      sperm donor with the most informative haplotype.
AB  - BACKGROUND: The study is aimed to describe a novel strategy that increases the
      accuracy and reliability of PGD in patients using sperm donation by pre-selecting
      the donor whose haplotype does not overlap the carrier's one. METHODS: A panel of
      4-9 informative polymorphic markers, flanking the mutation in carriers of
      autosomal dominant/X-linked disorders, was tested in DNA of sperm donors before
      PGD. Whenever the lengths of donors' repeats overlapped those of the women,
      additional donors' DNA samples were analyzed. The donor that demonstrated the
      minimal overlapping with the patient was selected for IVF. RESULTS: In 8 out of
      17 carriers the markers of the initially chosen donors overlapped the patients'
      alleles and 2-8 additional sperm donors for each patient were haplotyped. The
      selection of additional sperm donors increased the number of informative markers
      and reduced misdiagnosis risk from 6.00% +/- 7.48 to 0.48% +/-0.68. The PGD
      results were confirmed and no misdiagnosis was detected. CONCLUSIONS: Our study
      demonstrates that pre-selecting a sperm donor whose haplotype has minimal
      overlapping with the female's haplotype, is critical for reducing the
      misdiagnosis risk and ensuring a reliable PGD. This strategy may contribute to
      prevent the transmission of affected IVF-PGD embryos using a simple and
      economical procedure. TRIAL REGISTRATION: All procedures performed in studies
      involving human participants were in accordance with the ethical standards of the
      institutional and/or national research committee and with the 1964 Helsinki
      declaration and its later amendments or comparable ethical standards. DNA testing
      of donors was approved by the institutional Helsinki committee (registration
      number 319-08TLV, 2008). The present study was approved by the institutional
      Helsinki committee (registration number 0385-13TLV, 2013).

PMID- 28446184
TI  - Results of 167 consecutive cases of acetabular fractures using the Kocher
      Langenbeck approach: a case series.
AB  - BACKGROUND: Acetabular fractures are quite challenging injuries for the
      orthopedic surgeon because of their low incidence and their deep and complex
      anatomy. The objective of this study was to evaluate surgeon-independent
      parameters that might influence radiographic outcome and early complication rates
      of high-energy acetabular fractures treated by open reduction and internal
      fixation via the Kocher-Langenbeck approach, the golden standard for posterior
      access. METHODS: One hundred sixty-seven consecutive patients (111 males and 56
      females) with a mean age of 41.8 years and a mean follow-up period of 10 months
      were surgically treated by one experienced surgeon at a level I trauma center
      within 10 years. To quantify the radiographic outcome, the Matta, Brooker, and
      Epstein grades were used. Posttraumatic arthritis and avascular necrosis of the
      femoral head (defined as Helfet grades 3 or 4 and Ficat/Arlet stages 3 or 4,
      respectively) were evaluated. Furthermore, subgroup analyses according to
      fracture type, age, and gender were performed for each outcome measure and
      complication (infection, hemorrhagic shock, revision surgery, nerve damage, and
      need of a total hip arthroplasty). RESULTS: 65 A1, 34 A2, 51 B1, and 17 B2
      fractures were identified according to the AO/ASIF classification. Of all
      patients, reduction was rated anatomic in 63.5%, imperfect in 22.2%, and poor in
      14.4%. Degenerative changes were observed in 49.7%; 37.9% were affected by
      heterotopic ossification, 21.6% by posttraumatic arthritis, and 5.4% by avascular
      necrosis of the femoral head. Fifteen percent were diagnosed with a nerve damage,
      and 4.8% sustained an infection. Total hip arthroplasty was performed in 10.2%.
      Revision surgery due to secondary loss of reduction, seroma/hematoma, and wound
      infection was indicated in 6.0%. CONCLUSIONS: Fracture type, age, and gender are
      prognostic factors for the surgical outcome after ORIF of high-energy acetabular
      fractures.

PMID- 28446183
TI  - Effect of different artificial shrinkage methods, when applied before blastocyst
      vitrification, on perinatal outcomes.
AB  - BACKGROUND: In recent years, single blastocyst transfer combined with
      vitrification has been applied widely, which can maximize the cumulative
      pregnancy rate in per oocyte retrieval cycles and minimize the multiple pregnancy
      rate. Thus, the guarantee for these is the effectiveness of vitrified blastocyst.
      Studies has shown that AS of the blastocoel cavity prior to vitrification can
      reduce injuries, increase the thawed blastocyst survival rate and implantation
      rate. Several AS methods have been established. However, only a few studies have
      compared the effectiveness and safety of these AS methods. In this study, we
      aimed to compare the clinical outcomes and neonatal outcomes in FET cycles with
      single blastocyst that were artificially shrunk before vitrification by either
      LAS or MNAS method. METHODS: A retrospective comparative study of FET cycles in
      infertile patients which were at our clinic between January 2013 and December
      2014. These FET cycles were divided into two groups by the shrinking methods used
      before vitrification and the clinical and neonatal outcomes were assessed.
      RESULTS: There were no statistically differences in blastocyst survival rates
      (95.40% vs 94.05%, P > 0.05) between the LAS and MNAS groups. However, compared
      with MNAS, LAS improved the warmed blastocyst implantation/clinical pregnancy
      rate (60.82% vs 54.37%, P < 0.05), live birth rate (50.43% vs 45.22%, P < 0.05)
      and also increased the monozygotic twin rate (4.07% vs 1.73%, P < 0.05). There
      were no differences in the average gestational weeks (38.83 +/- 1.57 vs 38.74 +/-
      1.75), premature birth rate (0.30% vs 0.49%), average birth weight (3217.89 +/-
      489.98 g vs 3150.88 +/- 524.03 g), low birth weight rate (5.60% vs 8.63%) and
      malformation rate (0.59% vs 0.48%) (P > 0.05). CONCLUSIONS: No significant
      differences in neonatal outcomes were observed, while in clinical outcomes, LAS
      improved the warmed blastocyst implantation/clinical pregnancy rate and live
      birth rate markedly, there was also an increased risk of monozygotic twin
      pregnancies.

PMID- 28446185
TI  - Evidence-based policymaking is not like evidence-based medicine, so how far
      should you go to bridge the divide between evidence and policy?
AB  - There is extensive health and public health literature on the 'evidence-policy
      gap', exploring the frustrating experiences of scientists trying to secure a
      response to the problems and solutions they raise and identifying the need for
      better evidence to reduce policymaker uncertainty. We offer a new perspective by
      using policy theory to propose research with greater impact, identifying the need
      to use persuasion to reduce ambiguity, and to adapt to multi-level policymaking
      systems.We identify insights from secondary data, namely systematic reviews,
      critical analysis and policy theories relevant to evidence-based policymaking.
      The studies are drawn primarily from countries such as the United States, United
      Kingdom, Canada, Australia and New Zealand. We combine empirical and normative
      elements to identify the ways in which scientists can, do and could influence
      policy.We identify two important dilemmas, for scientists and researchers, that
      arise from our initial advice. First, effective actors combine evidence with
      manipulative emotional appeals to influence the policy agenda - should scientists
      do the same, or would the reputational costs outweigh the policy benefits?
      Second, when adapting to multi-level policymaking, should scientists prioritise
      'evidence-based' policymaking above other factors? The latter includes governance
      principles such the 'co-production' of policy between local public bodies,
      interest groups and service users. This process may be based primarily on values
      and involve actors with no commitment to a hierarchy of evidence.We conclude that
      successful engagement in 'evidence-based policymaking' requires pragmatism,
      combining scientific evidence with governance principles, and persuasion to
      translate complex evidence into simple stories. To maximise the use of scientific
      evidence in health and public health policy, researchers should recognise the
      tendency of policymakers to base judgements on their beliefs, and shortcuts based
      on their emotions and familiarity with information; learn 'where the action is',
      and be prepared to engage in long-term strategies to be able to influence policy;
      and, in both cases, decide how far you are willing to go to persuade policymakers
      to act and secure a hierarchy of evidence underpinning policy. These are value
      driven and political, not just 'evidence-based', choices.

PMID- 28446186
TI  - Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann
      cell-mediated axonal protection.
AB  - BACKGROUND: Fingolimod, a sphingosine-1-phosphate receptor modulator with well
      described immunomodulatory properties involving peripheral immune cell
      trafficking, was the first oral agent approved for the treatment of relapsing
      remitting multiple sclerosis. Analogous immunomodulatory treatment options for
      chronic peripheral autoimmune neuropathies are lacking. METHODS: We tested
      fingolimod in the animal model of experimental autoimmune neuritis in Lewis rat.
      Six to eight-week-old female rats were immunized with P2 peptide and from this
      day on treated with fingolimod. Histology of the sciatic nerve was done to
      analyze T cell and macrophage cell count, intercellular adhesion molecule (ICAM)
      and amyloid precursor protein (APP) expression, as well as apoptotic Schwann cell
      counts. RESULTS: Preventive oral treatment with 0.1 mg/kg up to 3 mg/kg
      fingolimod once daily dissolved in rapeseed oil completely ameliorated clinical
      neuritis signs. It reduced circulating peripheral blood T cells and infiltrating
      T cells and macrophages in the sciatic nerve, whereas at the same time, it
      preserved blood-nerve barrier impermeability. Most importantly, fingolimod showed
      beneficial properties on the pathogenic process as indicated by fewer apoptotic
      Schwann cells and a lower amount of amyloid precursor protein indicative of
      axonal damage at the peak of disease course. CONCLUSIONS: Taken together, orally
      administered low-dose fingolimod showed an impressive immunomodulatory effect in
      the rat model of experimental autoimmune neuritis. Our current observations
      introduce fingolimod as an attractive treatment option for neuritis patients.

PMID- 28446187
TI  - Characterisation of the natural environment: quantitative indicators across
      Europe.
AB  - BACKGROUND: The World Health Organization recognises the importance of natural
      environments for human health. Evidence for natural environment-health
      associations comes largely from single countries or regions, with varied
      approaches to measuring natural environment exposure. We present a standardised
      approach to measuring neighbourhood natural environment exposure in cities in
      different regions of Europe. METHODS: The Positive Health Effects of the Natural
      Outdoor environment in TYPical populations of different regions in Europe
      (PHENOTYPE) study aimed to explore the mechanisms linking natural environment
      exposure and health in four European cities (Barcelona, Spain; Doetinchem, the
      Netherlands; Kaunas, Lithuania; and Stoke-on-Trent, UK). Common GIS protocols
      were used to develop a hierarchy of natural environment measures, from simple
      measures (e.g., NDVI, Urban Atlas) using Europe-wide data sources, to detailed
      measures derived from local data that were specific to mechanisms thought to
      underpin natural environment-health associations (physical activity, social
      interaction, stress reduction/restoration). Indicators were created around
      residential addresses for a range of straight line and network buffers (100 m-1
      km). RESULTS: For simple indicators derived from Europe-wide data, we observed
      differences between cities, which varied with different indicators (e.g., Kaunas
      and Doetinchem had equal highest mean NDVI within 100 m buffer, but mean distance
      to nearest natural environment in Kaunas was more twice that in Doetinchem). Mean
      distance to nearest natural environment for all cities suggested that most
      participants lived close to some kind of natural environments (64 +/- 58-363 +/-
      281 m; mean 180 +/- 204 m). The detailed classification highlighted marked
      between-city differences in terms of prominent types of natural environment.
      Indicators specific to mechanisms derived from this classification also captured
      more variation than the simple indicators. Distance to nearest and count
      indicators showed clear differences between cities, and those specific to the
      mechanisms showed within-city differences for Barcelona and Doetinchem.
      CONCLUSIONS: This paper demonstrates the feasibility and challenges of creating
      comparable GIS-derived natural environment exposure indicators across diverse
      European cities. Mechanism-specific indicators showed within- and between-city
      variability that supports their utility for ecological studies, which could
      inform more specific policy recommendations than the traditional proxies for
      natural environment access.

PMID- 28446188
TI  - Phosphorylation by mTORC1 stablizes Skp2 and regulates its oncogenic function in
      gastric cancer.
AB  - BACKGROUND: Both mTOR and Skp2 play critical roles in gastric cancer (GC)
      tumorigenesis. However, potential mechanisms for the association between these
      two proteins remains unidentified. METHODS: The regulatory role for mTORC1 in
      Skp2 stability was tested using ubiquitination assay. The functions of p-Skp2
      (phosphorylation of Skp2) were studied in vitro and in vivo. Expression of p-Skp2
      and p-mTOR (phosphorylation of mTOR) were shown in GC lines and in 169 human
      primary GC tissues. RESULTS: mTORC1 can directly interact with Skp2 and
      phosphorylated Skp2 at Ser64, which sequentially protect Skp2 from ubiquitination
      and degradation. Furthermore, the phospho-deficient p-Skp2 (S64) mutant
      significantly suppresses GC cell proliferation and tumorigenesis. The expression
      of p-Skp2 was associated with p-mTOR in GC cell lines and tissues. Interestingly,
      the combination of p-Skp2 and p-mTOR was a better predictor of survival than
      either factor alone. CONCLUSION: The mTORC1 function to regulate Skp2 by Ser64
      phosphorylation may represent an oncogenic event in GC tumorigenesis. Moreover,
      our study also indicates that Skp2 Ser64 expression is a potential indicator in
      the treatment of GC patients using mTORC1 inhibitor.

PMID- 28446189
TI  - Television viewing time as a risk factor for frailty and functional limitations
      in older adults: results from 2 European prospective cohorts.
AB  - BACKGROUND: Sedentariness is an important risk factor for poor health. The main
      objective of this work was to examine the prospective association between
      television viewing time and indicators of physical function, mobility, agility,
      and frailty. METHODS: Data came from two independent cohorts of community
      dwelling older adults: the Seniors-ENRICA (n = 2392, 3.5 year follow-up), and the
      ELSA (n = 3989, 3.9 year follow-up). At baseline, television viewing and other
      sedentary behaviors were ascertained using interviewer-administered
      questionnaires. In the Seniors-ENRICA cohort overall physical function at
      baseline and follow-up was assessed using the physical component summary (PCS) of
      the SF-12 Health Survey. Measures for incident mobility and agility limitations
      in both cohorts were based on standardized questions, and incident frailty was
      measured with the Fried criteria. Analyses were adjusted for the main
      confounders, including physical activity at baseline. Results across cohorts were
      pooled using a random effects model. RESULTS: Lower (worse) scores in the PCS
      were observed among those in the highest (vs. the lowest) tertile of television
      viewing time (b-coefficient:-1.66; 95% confidence interval:-2.81,-0.52; p-trend =
      0.01). Moreover, the pooled odds ratios (95% CIs) for mobility limitations for
      the second and third (vs. the lowest) tertile of television viewing were 1.00
      (0.84, 1.20) and 1.17 (1.00, 1.38); p-trend = 0.12, respectively. The
      corresponding results for agility limitations were 1.18 (0.97, 1.44) and 1.25
      (1.03, 1.51); p-trend = 0.02. Results for incident frailty were 1.10 (0.80, 1.51)
      and 1.47 (1.09, 1.97); p-trend = 0.03. No association between other types of
      sedentary behavior (time seated at the computer, while commuting, lying in the
      sun, listening to music/reading, internet use) and risk of functional limitations
      was found. CONCLUSIONS: Among older adults, longer television viewing time is
      prospectively associated with limitations in physical function independently of
      physical activity.

PMID- 28446190
TI  - Recognition of Plasmodium falciparum mature gametocyte-infected erythrocytes by
      antibodies of semi-immune adults and malaria-exposed children from Gabon.
AB  - BACKGROUND: Transmission of malaria from man to mosquito depends on the presence
      of gametocytes, the sexual stage of Plasmodium parasites in the infected host.
      Naturally acquired antibodies against gametocytes exist and may play a role in
      controlling transmission by limiting the gametocyte development in the
      circulation or by interrupting gamete development and fertilization in the
      mosquito following ingestion. So far, most studies on antibody responses to
      sexual stage antigens have focused on a subset of gametocyte-surface antigens,
      even though inhibitory Ab responses to other gametocyte antigens might also play
      a role in controlling gametocyte density and fertility. Limited information is
      available on natural antibody response to the surfaces of gametocyte-infected
      erythrocytes. METHODS: Ab responses to surface antigens of erythrocytes infected
      by in vitro differentiated Plasmodium falciparum mature gametocytes were
      investigated in sera of semi-immune adults and malaria-exposed children. In
      addition, the effect of immunization with GMZ2, a blood stage malaria vaccine
      candidate, and the effect of intestinal helminth infection on the development of
      immunity to gametocytes of P. falciparum was evaluated in malaria-exposed
      children and adults from Gabon. Serum samples from two Phase I clinical trials
      conducted in Gabon were analysed by microscopic and flow-cytometric
      immunofluorescence assay. RESULTS: Adults had a higher Ab response compared to
      children. Ab reactivity was significantly higher after fixation and
      permeabilization of parasitized erythrocytes. Following vaccination with the
      malaria vaccine candidate GMZ2, anti-gametocyte Ab concentration decreased in
      adults compared to baseline. Ab response to whole asexual stage antigens had a
      significant but weak positive correlation to anti-gametocyte Ab responses in
      adults, but not in children. Children infected with Ascaris lumbricoides had a
      significantly higher anti-gametocyte Ab response compared to non-infected
      children. CONCLUSION: The current data suggest that antigens exposed on the
      gametocyte-infected red blood cells are recognized by serum antibodies from
      malaria-exposed children and semi-immune adults. This anti-gametocyte immune
      response may be influenced by natural exposure and vaccination. Modulation of the
      natural immune response to gametocytes by co-infecting parasites should be
      investigated further and may have an important impact on malaria control
      strategies.

PMID- 28446191
TI  - Longitudinal analysis of serum oxylipin profile as a novel descriptor of the
      inflammatory response to surgery.
AB  - BACKGROUND: Oxylipins are potent lipid mediators demonstrated to initiate and
      regulate inflammation yet little is known regarding their involvement in the
      response to surgical trauma. As key modulators of the inflammatory response,
      oxylipins have the potential to provide novel insights into the physiological
      response to surgery and the pathophysiology of post-operative complications. We
      aimed to investigate the effects of major surgery on longitudinal oxylipin
      profile. METHODS: Adults patients undergoing elective laparoscopic or open
      colorectal resections were included. Primary outcomes were serum oxylipin profile
      quantified by ultra high-performance liquid chromatography-mass spectrometry,
      serum white cell count and C-reactive protein concentration. Serum samples were
      taken at three time-points: pre-operative (day zero), early post-operative (day
      one) and late post-operative (day four/five). RESULTS: Some 55 patients were
      included, of which 33 (60%) underwent surgery that was completed
      laparoscopically. Pre-operative oxylipin profiles were characterised by marked
      heterogeneity but surgery induced a common shift resulting in more homogeneity at
      the early post-operative time-point. By the late post-operative phase, oxylipin
      profiles were again highly variable. This evolution was driven by time-dependent
      changes in specific oxylipins. Notably, the levels of several oxylipins with anti
      inflammatory properties (15-HETE and four regioisomers of DHET) were reduced at
      the early post-operative point before returning to baseline by the late post
      operative period. In addition, levels of the pro-inflammatory 11-HETE rose in the
      early post-operative phase while levels of anti-thrombotic mediators (9-HODE and
      13-HODE) fell; concentrations of all three oxylipins then remained fairly static
      from early to late post-operative phases. Compared to those undergoing
      laparoscopic surgery, patients undergoing open surgery had lower levels of some
      anti-inflammatory oxylipins (8,9-DHET and 17-HDoHE) in addition to reduced
      concentrations of anti-thrombotic mediators (9-HODE and 13-HODE) with increased
      concentration of their pro-thrombotic counterpart (TxB2). CONCLUSIONS: Serum
      oxylipin profile is modified by surgical intervention and may even be sensitive
      to the degree of surgical trauma and therefore represents a novel descriptor of
      the surgical systemic inflammatory response.

PMID- 28446192
TI  - Prospective clinical and radiographic evaluation of an allogeneic bone matrix
      containing stem cells (Trinity Evolution(r) Viable Cellular Bone Matrix) in
      patients undergoing two-level anterior cervical discectomy and fusion.
AB  - BACKGROUND: Trinity Evolution(r) (TE), a viable cellular bone allograft,
      previously demonstrated high fusion rates and no safety-related concerns after
      single-level anterior cervical discectomy and fusion (ACDF) procedures. This
      prospective multicenter clinical study was performed to assess the radiographic
      and clinical outcomes of TE in subjects undergoing two-level ACDF procedures.
      METHODS: In a prospective, multicenter study, 40 subjects that presented with
      symptomatic cervical degeneration at two adjacent vertebral levels underwent
      instrumented ACDF using TE autograft substitute in a polyetherethereketone (PEEK)
      cage. At 12 months, radiographic fusion status was evaluated by dynamic motion
      plain radiographs and thin cut CT with multiplanar reconstruction by a panel that
      was blinded to clinical outcome. Fusion success was defined by angular motion
      (<=4 degrees ) and the presence of bridging bone across the adjacent vertebral
      endplates. Clinical pain and function assessments included the Neck Disability
      Index (NDI), neck and arm pain as evaluated by visual analog scales (VAS), and SF
      36 at both 6 and 12 months. RESULTS: At both 6 and 12 months, all clinical
      outcome scores (SF-36, NDI, and VAS pain) improved significantly (p < 0.05)
      compared to baseline values. There were no adverse events or infections that were
      attributed to the graft material, no subjects that required revisions, and no
      significant decreases to mean neurological evaluations at any time as compared to
      baseline. At 12 months, the per subject and per level fusion rate was 89.4 and
      93.4%, respectively. Subgroup analysis of subjects with risk factors for
      pseudoarthrosis (current or former smokers, diabetic, or obese/extremely obese)
      compared to those without risk factors demonstrated no significant differences in
      fusion rates. CONCLUSIONS: Patients undergoing two-level ACDF with TE in
      combination with a PEEK interbody spacer and supplemental anterior fixation had a
      high rate of fusion success without any serious adverse events related to the
      graft material. TRIAL REGISTRATION: Trinity Evolution in Anterior Cervical
      Disectomy and Fusion (ACDF) NCT00951938.

PMID- 28446193
TI  - Liver morphometrics and metabolic blood profile across divergent phenotypes for
      feed efficiency in the bovine.
AB  - BACKGROUND: Feed costs are a major expense in the production of beef cattle.
      Individual variation in the efficiency of feed utilization may be evident through
      feed efficiency-related phenotypes such as those related to major energetic
      sinks. Our objectives were to assess the relationships between feed efficiency
      with liver morphometry and metabolic blood profile in feedlot beef cattle.
      METHODS: Two populations (A = 112 and B = 45) of steers were tested for feed
      efficiency. Blood from the 12 most (efficient) and 12 least feed inefficient
      (inefficient) steers from population A was sampled hourly over the circadian
      period. Blood plasma samples were submitted for analysis on albumin, aspartate
      aminotransferase, gamma-glutamyl transpeptidase urea, cholesterol, creatinine,
      alkaline phosphatase, creatine kinase, lipase, carbon dioxide, beta
      hydroxybutyrate, acetate and bile acids. Liver tissue was also harvested from 24
      steers that were blood sampled from population A and the 10 steers with divergent
      feed efficiency in each tail of population B was sampled for microscopy at
      slaughter. Photomicroscopy images were taken using the portal triad and central
      vein as landmarks. Histological quantifications included cross-sectional
      hepatocyte perimeter and area, hepatocyte nuclear area and nuclei area as
      proportion of the hepatocyte area. The least square means comparison between
      efficient and inefficient steers for productive performance and liver morphometry
      and for blood analytes data were analyzed using general linear model and mixed
      model procedures of SAS, respectively. RESULTS: No differences were observed for
      liver weight; however, efficient steers had larger hepatocyte (i.e. hepatocyte
      area at the porta triad 323.31 vs. 286.37 um2) and nuclei dimensions at portal
      triad and central vein regions, compared with inefficient steers. The metabolic
      profile indicated efficient steers had lower albumin (36.18 vs. 37.65 g/l) and
      cholesterol (2.62 vs. 3.05 mmol/l) and higher creatinine (118.59 vs. 110.50
      mmol/l) and carbon dioxide (24.36 vs. 23.65 mmol/l) than inefficient steers.
      CONCLUSIONS: Improved feed efficiency is associated with increased metabolism by
      the liver (enlarged hepatocytes and no difference on organ size), muscle (higher
      creatinine) and whole body (higher carbon dioxide); additionally, efficient
      steers had reduced bloodstream pools of albumin and cholesterol. These metabolic
      discrepancies between feed efficient and inefficient cattle may be determinants
      of productive performance.

PMID- 28446194
TI  - Knowledge attitude and practice regarding diabetes mellitus among Nondiabetic and
      diabetic study participants in Bangladesh.
AB  - BACKGROUND: Increased awareness amongst large population groups is a major
      determinant for the prevention of diabetes and its complications as well as
      related metabolic disorders. Knowledge and attitude are the principal markers of
      awareness that need to be studied in various population groups in specific racial
      and cultural contexts. The present study was undertaken to explore knowledge,
      attitude and practice (KAP) regarding -diabetes mellitus (DM) among nondiabetic
      (nonDM) and type 2 diabetes mellitus (T2DM) patients in Bangladesh. METHODS: A
      cross-sectional study was conducted among 18,697 adults (aged 18 years and above;
      7796 male and 10,901 female; 6780 nonDM and 11,917 T2DM) selected purposively
      from the OPD of 19 healthcare centres in and around Dhaka and in northern parts
      of Bangladesh. KAP were assessed by a pre-structured, interviewer-administered
      questionnaire and categorised using predefined scores of poor (<mean - 1 SD),
      average (mean +/- 1 SD) and good (>mean + 1 SD). Univariate and bivariate
      statistical analysis were done as appropriate. Multivariate linear regression was
      done to examine the association between diabetes related KAP and other
      covariates. RESULTS: The mean (+/-SD) age (years) of all the study participants
      was 46 +/- 14, mean BMI 24.4 +/- 4.1 and mean waist-hip ratio (WHR) was 0.93 +/-
      0.07. The proportion of poor, average and good knowledge scores among T2DM
      subjects were 17%, 68% and 15% respectively. The corresponding values for
      attitude score were 23%, 67% and 10% respectively. The KAP regarding diabetes was
      found to be better among people who were living with diabetes compared to their
      counterparts. DM males showed better knowledge and practice regarding diabetes,
      compared to nonDM counterparts (M +/- SD; 44.18 +/- 16.13 vs 40.88 +/- 15.62, p =
      <0.001; 66.00 +/- 29.68 vs 64.21 +/- 31.79, p < 0.001, respectively). Females
      showed better attitude score compared to males. Overall KAP were found to be
      significantly higher (p < 0.001) in middle aged (31-50 years) participants in
      each group. Participants from urban residents, higher educational background and
      upper socio-economic class demonstrated significantly greater score in terms of
      KAP in both nonDM and T2DM groups (p < 0.001). On linear regression analysis,
      knowledge scores correlated strongly with education, income, residence, diabetic
      state, BMI and attitude. CONCLUSIONS: The overall level of knowledge and practice
      concerning diabetes among Bangladeshi population is average, but the overall
      level of attitude is good both in nonDM and T2DM subjects. To prevent diabetes
      and its complications there is an urgent need for coordinated educational
      campaigns with a prioritized focus on poorer, rural and less educated groups.

PMID- 28446195
TI  - Mature leaf concentrate of Sri Lankan wild type Carica papaya Linn. modulates
      nonfunctional and functional immune responses of rats.
AB  - BACKGROUND: The leaf concentrate of Carica papaya is a traditionally acclaimed
      immunomodulatory remedy against numerous diseases; nonetheless comprehensive
      scientific validation of this claim is limited. The present study thus
      investigated the immunomodulatory potential of Carica papaya mature leaf
      concentrate (MLCC) of the Sri Lankan wild type cultivar using nonfunctional and
      functional immunological assays. METHODS: Wistar rats (N = 6/ group) were orally
      gavaged with 3 doses (0.18, 0.36 and 0.72 ml/100g body weight) of the MLCC once
      daily for 3 consecutive days. Selected nonfunctional (enumeration of immune cells
      and cytokine levels) and functional (cell proliferation and phagocytic activity)
      immunological parameters, and acute toxic effects were determined using standard
      methods. Effect of the MLCC (31.25, 62.5, 125, 250, 500 and 1000 MUg/ml) on ex
      vivo proliferation of bone marrow cells (BMC) and splenocytes (SC), and in vitro
      phagocytic activity of peritoneal macrophages (PMs), and their corresponding
      cytokine responses were evaluated. The phytochemical profile of the MLCC was
      established using liquid chromatography-mass spectrometry (LS-MS) and Gas
      chromatography-mass spectrometry (GC-MS). RESULTS: Counts of rat platelets, total
      leukocytes, lymphocyte and monocyte sub populations, and BMCs were significantly
      augmented by oral gavage of the MLCC (p < 0.05). The highest MLCC dose tested
      herein significantly reduced pro inflammatory cytokines, Interleukin 6 (IL-6) and
      Tumor Necrosis Factor alpha (TNF alpha) levels of rats (p < 0.05). The in vivo
      phagocytic index of rat PMs significantly increased by oral gavage of all three
      doses of the MLCC (p < 0.05). In vitro phagocytic activity of rat PMs were
      enhanced by the MLCC and triggered a Th1 biased cytokine response. The MLCC at
      low concentrations elicited ex vivo proliferation of BMC (31.25 MUg/ml) and SC
      (31.25 and 62.5 MUg/ml) respectively. Conversely, high concentrations (500 and
      1000 MUg/ml) exhibited cytotoxicity of both BMC and SC with significant
      modulation of cytokines. Chemical profile of the MLCC revealed the presence of
      several immunomodulatory compounds. The oral gavage of the MLCC was found to be
      safe in terms of both hepatic and renal toxicities. CONCLUSION: The present study
      established that the mature leaf concentrate (MLCC) of Carica papaya Sri Lankan
      wild type cultivar is orally active, safe and effectively modulates nonfunctional
      and functional immunological parameters of rats that unequivocally corroborate
      the traditional medical claims.

PMID- 28446196
TI  - Self-reported general health, physical distress, mental distress, and activity
      limitation by US county, 1995-2012.
AB  - BACKGROUND: Metrics based on self-reports of health status have been proposed for
      tracking population health and making comparisons among different populations.
      While these metrics have been used in the US to explore disparities by sex,
      race/ethnicity, and socioeconomic position, less is known about how self-reported
      health varies geographically. This study aimed to describe county-level trends in
      the prevalence of poor self-reported health and to assess the face validity of
      these estimates. METHODS: We applied validated small area estimation methods to
      Behavioral Risk Factor Surveillance System data to estimate annual county-level
      prevalence of four measures of poor self-reported health (low general health,
      frequent physical distress, frequent mental distress, and frequent activity
      limitation) from 1995 and 2012. We compared these measures of poor self-reported
      health to other population health indicators, including risk factor prevalence
      (smoking, physical inactivity, and obesity), chronic condition prevalence
      (hypertension and diabetes), and life expectancy. RESULTS: We found substantial
      geographic disparities in poor self-reported health. Counties in parts of South
      Dakota, eastern Kentucky and western West Virginia, along the Texas-Mexico
      border, along the southern half of the Mississippi river, and in southern Alabama
      generally experienced the highest levels of poor self-reported health. At the
      county level, there was a strong positive correlation among the four measures of
      poor self-reported health and between the prevalence of poor self-reported health
      and the prevalence of risk factors and chronic conditions. There was a strong
      negative correlation between prevalence of poor self-reported health and life
      expectancy. Nonetheless, counties with similar levels of poor self-reported
      health experienced life expectancies that varied by several years. Changes over
      time in life expectancy were only weakly correlated with changes in the
      prevalence of poor self-reported health. CONCLUSIONS: This analysis adds to the
      growing body of literature documenting large geographic disparities in health
      outcomes in the United States. Health metrics based on self-reports of health
      status can and should be used to complement other measures of population health,
      such as life expectancy, to identify high need areas, efficiently allocate
      resources, and monitor geographic disparities.

PMID- 28446197
TI  - Re-directing bacterial microcompartment systems to enhance recombinant expression
      of lysis protein E from bacteriophage phiX174 in Escherichia coli.
AB  - BACKGROUND: Recombinant expression of toxic proteins remains a challenging
      problem. One potential method to shield toxicity and thus improve expression of
      these proteins is to encapsulate them within protein compartments to sequester
      them away from their targets. Many bacteria naturally produce so-called bacterial
      microcompartments (BMCs) in which enzymes comprising a biosynthetic pathway are
      encapsulated in a proteinaeous shell, which is in part thought to shield the
      cells from the toxicity of reaction intermediates. As a proof-of-concept, we
      attempted to encapsulate toxic, lysis protein E (E) from bacteriophage phiX174
      inside recombinant BMCs to enhance its expression and achieve higher yields
      during downstream purification. RESULTS: E was fused with various N-terminal BMC
      targeting tags (PduP-, PduD-, and EutC-tags, 18-20 amino acids) and co-expressed
      with appropriate BMC shell proteins that associate with the tags and are required
      to form BMCs. Only BMC targeted E fusions, but not non-tagged E, could be
      successfully cloned, suggesting that the BMC tags reduce the toxicity of E. A
      PduP-tagged E system appeared to achieve the highest expression of E. Co
      expression of Pdu BMC shell proteins with PduP-E increased its expression by 20
      50%. Affinity purification of PduP-E via Ni-NTA in the presence of Empigen BB
      detergent yielded 270 ug of PduP-E per L of induced culture. Removal of the PduP
      tag via proteolysis resulted in a final yield of 200 ug of E per L of induced
      culture, a nearly order of magnitude (~sevenfold) improvement compared to prior
      reports. CONCLUSIONS: These results demonstrate improved expression of phiX174
      lysis protein E via re-directed BMC systems and ultimately higher E purification
      yields. Similar strategies can be used to enhance expression of other toxic
      proteins in recombinant Escherichia coli systems.

PMID- 28446198
TI  - Effect of anti-malarial interventions on trends of malaria cases, hospital
      admissions and deaths, 2005-2015, Ghana.
AB  - BACKGROUND: Since 2005, the Government of Ghana and its partners, in concerted
      efforts to control malaria, scaled up the use of artemisinin-based combination
      therapy (ACT) and insecticide-treated nets (ITNs). Beginning in 2011, a mass
      campaign of long-lasting insecticidal nets (LLINs) was implemented, targeting all
      the population. The impact of these interventions on malaria cases, admissions
      and deaths was assessed using data from district hospitals. METHODS: Records of
      malaria cases and deaths and availability of ACT in 88 hospitals, as well as at
      district level, ITN distribution, and indoor residual spraying were reviewed.
      Annual proportion of the population potentially protected by ITNs was estimated
      with the assumption that each LLIN covered 1.8 persons for 3 years. Changes in
      trends of cases and deaths in 2015 were estimated by segmented log-linear
      regression, comparing trends in post-scale-up (2011-2015) with that of pre-scale
      up (2005-2010) period. Trends of mortality in children under 5 years old from
      population-based household surveys were also compared with the trends observed in
      hospitals for the same time period. RESULTS: Among all ages, the number of
      outpatient malaria cases (confirmed and presumed) declined by 57% (95% confidence
      interval [CI], 47-66%) by first half of 2015 (during the post-scale-up) compared
      to the pre-scale-up (2005-2010) period. The number of microscopically confirmed
      cases decreased by 53% (28-69%) while microscopic testing was stable. Test
      positivity rate (TPR) decreased by 41% (19-57%). The change in malaria admissions
      was insignificant while malaria deaths fell significantly by 65% (52-75%). In
      children under 5 years old, total malaria outpatient cases, admissions and deaths
      decreased by 50% (32-63%), 46% (19-75%) and 70% (49-82%), respectively. The
      proportion of outpatient malaria cases, admissions and deaths of all-cause
      conditions in both all ages and children under five also fell significantly by
      >30%. Similar decreases in the main malaria indicators were observed in the three
      epidemiological strata (coastal, forest, savannah). All-cause admissions
      increased significantly in patients covered by the National Health Insurance
      Scheme (NHIS) compared to the non-insured. The non-malaria cases and non-malaria
      deaths increased or remained unchanged during the same period. All-cause
      mortality for children under 5 years old in household surveys, similar to those
      observed in the hospitals, declined by 43% between 2008 and 2014. CONCLUSIONS:
      The data provide compelling evidence of impact following LLIN mass campaigns
      targeting all ages since 2011, while maintaining other anti-malarial
      interventions. Malaria cases and deaths decreased by over 50 and 65%,
      respectively. The declines were stronger in children under five. Test positivity
      rate in all ages decreased by >40%. The decrease in malaria deaths was against a
      backdrop of increased admissions owing to free access to hospitalization through
      the NHIS. The study demonstrated that retrospective health facility-based data
      minimize reporting biases to assess effect of interventions. Malaria control in
      Ghana is dependent on sustained coverage of effective interventions and
      strengthened surveillance is vital to monitor progress of these investments.

PMID- 28446199
TI  - Different determinants of exercise capacity in HFpEF compared to HFrEF.
AB  - BACKGROUND: Quality of life is as important as survival in heart failure (HF)
      patients. Controversies exist with regards to echocardiographic determinants of
      exercise capacity in HF, particularly in patients with preserved ejection
      fraction (HFpEF). The aim of this study was to prospectively examine
      echocardiographic parameters that correlate and predict functional exercise
      capacity assessed by 6 min walk test (6-MWT) in patients with HFpEF. METHODS: In
      111 HF patients (mean age 63 +/- 10 years, 47% female), an echo-Doppler study and
      a 6-MWT were performed in the same day. Patients were divided into two groups
      based on the 6-MWT distance (Group I: <= 300 m and Group II: >300 m). RESULTS:
      Group I were older (p = 0.008), had higher prevalence of diabetes (p = 0.027),
      higher baseline heart rate (p = 0.004), larger left atrium - LA (p = 0.001),
      longer LV filling time - FT (p = 0.019), shorter isovolumic relaxation time (p =
      0.037), shorter pulmonary artery acceleration time - PA acceleration time (p =
      0.006), lower left atrial lateral wall myocardial velocity (a') (p = 0.018) and
      lower septal systolic myocardial velocity (s') (p = 0.023), compared with Group
      II. Patients with HF and reduced EF (HFrEF) had lower hemoglobin (p = 0.007),
      higher baseline heart rate (p = 0.005), higher NT-ProBNP (p = 0.001), larger LA
      (p = 0.004), lower septal s', e', a' waves, and septal mitral annular plane
      systolic excursion (MAPSE), shorter PA acceleration time (p < 0.001 for all),
      lower lateral MAPSE, higher E/A & E/e', and shorter LVFT (p = 0.001 for all),
      lower lateral e' (p = 0.009), s' (p = 0.006), right ventricular e' and LA
      emptying fraction (p = 0.012 for both), compared with HFpEF patients. In
      multivariate analysis, only LA diameter [2.676 (1.242-5.766), p = 0.012], and
      diabetes [0.274 (0.084-0.898), p = 0.033] independently predicted poor 6-MWT
      performance in the group as a whole. In HFrEF, age [1.073 (1.012-1.137), p =
      0.018] and LA diameter [3.685 (1.348-10.071), p = 0.011], but in HFpEF, lateral
      s' [0.295 (0.099-0.882), p = 0.029], and hemoglobin level [0.497 (0.248-0.998), p
      = 0.049] independently predicted poor 6-MWT performance. CONCLUSIONS: In HF
      patients determinants of exercise capacity differ according to severity of
      overall LV systolic function, with left atrial enlargement in HFrEF and
      longitudinal systolic shortening in HFpEF as the the main determinants.

PMID- 28446200
TI  - Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and
      cancer prognosis.
AB  - BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the
      testis, but become activated during oncogenesis, so they have excellent potential
      as cancer-specific biomarkers. Evidence is starting to emerge to indicate that
      they also provide function(s) in the oncogenic programme. Human TEX19 is a
      recently identified CT gene, but a functional role for TEX19 in cancer has not
      yet been defined. METHODS: siRNA was used to deplete TEX19 levels in various
      cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo.
      Western blotting, fluorescence activated cell sorting and immunofluorescence were
      used to study the effect of TEX19 depletion in cancer cells and to localize TEX19
      in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were
      employed to determine the changes to the transcriptome of cancer cells depleted
      for TEX19 and Kaplan-Meier plots were generated to explore the relationship
      between TEX19 expression and prognosis for a range of cancer types. RESULTS:
      Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo
      restricts cellular proliferation/self-renewal/reduces tumour volume, indicating
      TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis
      of cells depleted for TEX19 indicates they enter a quiescent-like state and have
      subtle defects in S-phase progression. TEX19 is present in both the nucleus and
      cytoplasm in both cancerous cells and normal testis. In cancer cells,
      localization switches in a context-dependent fashion. Transcriptome analysis of
      TEX19 depleted cells reveals altered transcript levels of a number of cancer
      /proliferation-associated genes, suggesting that TEX19 could control oncogenic
      proliferation via a transcript/transcription regulation pathway. Finally, overall
      survival analysis of high verses low TEX19 expressing tumours indicates that
      TEX19 expression is linked to prognostic outcomes in different tumour types.
      CONCLUSIONS: TEX19 is required to drive cell proliferation in a range of cancer
      cell types, possibly mediated via an oncogenic transcript regulation mechanism.
      TEX19 expression is linked to a poor prognosis for some cancers and collectively
      these findings indicate that not only can TEX19 expression serve as a novel
      cancer biomarker, but may also offer a cancer-specific therapeutic target with
      broad spectrum potential.

PMID- 28446201
TI  - Anticonvulsant effects of antiaris toxicaria aqueous extract: investigation using
      animal models of temporal lobe epilepsy.
AB  - BACKGROUND: Antiaris toxicaria has previously shown anticonvulsant activity in
      acute animal models of epilepsy. The aqueous extract (AAE) was further
      investigated for activity in kindling with pentylenetetrazole and administration
      of pilocarpine and kainic acid which mimic temporal lobe epilepsy in various
      animal species. RESULTS: ICR mice and Sprague-Dawley rats were pre-treated with
      AAE (200-800 mg kg-1) and convulsive episodes induced using pentylenetetrazole,
      pilocarpine and kainic acid. The potential of AAE to prevent or delay onset and
      alter duration of seizures were measured. In addition, damage to hippocampal
      cells was assessed in kainic acid-induced status epilepticus test. 800 mg kg-1 of
      the extract suppressed the kindled seizure significantly (P < 0.05) as did
      diazepam. AAE also produced significant effect (P < 0.01) on latency to first
      myoclonic jerks and on total duration of seizures. The latency to onset of wet
      dog shakes was increased significantly (P < 0.05) by AAE on kainic acid
      administration. Carbamazepine and Nifedipine (30 mg kg-1) also delayed the onset.
      Histopathological examination of brain sections showed no protective effect on
      hippocampal cells by AAE and nifedipine. Carbamazepine offered better
      preservation of hippocampal cells in the CA1, CA2 and CA3 regions. CONCLUSION:
      Antiaris toxicaria may be effective in controlling temporal lobe seizures in
      rodents.

PMID- 28446203
TI  - Clinicians' views and experiences of offering two alternative consent pathways
      for participation in a preterm intrapartum trial: a qualitative study.
AB  - BACKGROUND: The Cord Pilot Trial compared alternative policies for timing of cord
      clamping at very preterm birth at eight UK hospitals. Preterm birth can be rapid
      and unexpected, allowing little time for the usual consent process. Therefore, in
      addition to the usual procedure for written consent, a two-stage pathway for
      consent for use when birth was imminent was developed. The aims of this study
      were to explore clinicians' views and experiences of offering two consent
      pathways for recruitment to a randomised trial of timing of cord clamping at very
      preterm birth. METHODS: This was a qualitative study using semi-structured
      interviews. Clinicians from eight hospitals in the UK who had been involved in
      offering consent to the Cord Pilot Trial were invited to take part in an
      interview. Clinicians were interviewed in person or by telephone. Interviews were
      analysed using inductive systematic thematic analysis. RESULTS: Seventeen
      clinicians who had either offered usual written consent only (n = 6) or both the
      two-stage pathway (with oral assent before the birth and written consent after
      the birth) and usual written consent (n = 11) were interviewed. Six themes were
      identified: (1) team approach to offering participation; (2) consent form as a
      record; (3) consent and participation as a continual process; (4) different
      consent pathways for different trials; (5) balance between time, information, and
      understanding; and (6) validity of consent. Overall, clinicians were supportive
      of the two-stage consent pathway. Some clinicians felt that in time-critical
      situations oral assent presented an advantage over the usual written consent as
      they provided information on a "need to know" basis. However, there was some
      concern about how much information should be given for oral assent, and how this
      is understood by women when birth is imminent. CONCLUSIONS: The two-stage pathway
      for consent developed for use in the Cord Pilot Trial when birth was imminent was
      acceptable to clinicians for comparable low-risk studies, although some concerns
      were raised about the practicalities of obtaining oral assent. TRIAL
      REGISTRATION: ISRCTN Registry, ISRCTN21456601 . Registered on 28 February 2013.

PMID- 28446204
TI  - Erratum to: Antifilarial activity of diterpenoids from Taxodium distichum.

PMID- 28446202
TI  - Analyzing the genes related to Alzheimer's disease via a network and pathway
      based approach.
AB  - BACKGROUND: Our understanding of the molecular mechanisms underlying Alzheimer's
      disease (AD) remains incomplete. Previous studies have revealed that genetic
      factors provide a significant contribution to the pathogenesis and development of
      AD. In the past years, numerous genes implicated in this disease have been
      identified via genetic association studies on candidate genes or at the genome
      wide level. However, in many cases, the roles of these genes and their
      interactions in AD are still unclear. A comprehensive and systematic analysis
      focusing on the biological function and interactions of these genes in the
      context of AD will therefore provide valuable insights to understand the
      molecular features of the disease. METHOD: In this study, we collected genes
      potentially associated with AD by screening publications on genetic association
      studies deposited in PubMed. The major biological themes linked with these genes
      were then revealed by function and biochemical pathway enrichment analysis, and
      the relation between the pathways was explored by pathway crosstalk analysis.
      Furthermore, the network features of these AD-related genes were analyzed in the
      context of human interactome and an AD-specific network was inferred using the
      Steiner minimal tree algorithm. RESULTS: We compiled 430 human genes reported to
      be associated with AD from 823 publications. Biological theme analysis indicated
      that the biological processes and biochemical pathways related to
      neurodevelopment, metabolism, cell growth and/or survival, and immunology were
      enriched in these genes. Pathway crosstalk analysis then revealed that the
      significantly enriched pathways could be grouped into three interlinked modules
      neuronal and metabolic module, cell growth/survival and neuroendocrine pathway
      module, and immune response-related module-indicating an AD-specific immune
      endocrine-neuronal regulatory network. Furthermore, an AD-specific protein
      network was inferred and novel genes potentially associated with AD were
      identified. CONCLUSION: By means of network and pathway-based methodology, we
      explored the pathogenetic mechanism underlying AD at a systems biology level.
      Results from our work could provide valuable clues for understanding the
      molecular mechanism underlying AD. In addition, the framework proposed in this
      study could be used to investigate the pathological molecular network and genes
      relevant to other complex diseases or phenotypes.

PMID- 28446205
TI  - Response to the Letter to the Editor by Rob Armstrong.
AB  - In a recent Letter to the Editor, Armstrong raises concern that the design of the
      study reported by Six et al. was not consistent with the product label for
      treatment of Amblyomma americanum, since fluralaner was not re-administered 56
      days after the initial treatment. The Authors disagree with this assessment and
      confirm that the design was appropriate, and therefore the results and
      conclusions for the entire study period are valid.

PMID- 28446206
TI  - Cooperation of neurotrophin receptor TrkB and Her2 in breast cancer cells
      facilitates brain metastases.
AB  - BACKGROUND: Patients with primary breast cancer that is positive for human
      epidermal growth factor receptor 2 (Her2+) have a high risk of developing
      metastases in the brain. Despite gains with systemic control of Her2+ disease
      using molecular therapies, brain metastases remain recalcitrant to therapeutic
      discovery. The clinical predilection of Her2+ breast cancer cells to colonize the
      brain likely relies on paracrine mechanisms. The neural niche poses unique
      selection pressures, and neoplastic cells that utilize the brain microenvironment
      may have a survival advantage. METHODS: Tropomyosin-related kinase B (TrkB),
      Her2, and downstream targets were analyzed in primary breast cancer, breast-to
      brain metastasis (BBM) tissues, and tumor-derived cell lines using quantitative
      real-time PCR, western blot, and immunohistochemical assessment. TrkB function on
      BBM was confirmed with intracranial, intracardiac, or mammary fat pad xenografts
      in non-obese diabetic/severe combined immunodeficiency mice. The function of
      brain-derived neurotrophic factor (BDNF) on cell proliferation and TrkB/Her2
      signaling and interactions were confirmed using selective shRNA knockdown and
      selective inhibitors. The physical interaction of Her2-TrkB was analyzed using
      electron microscopy, co-immunoprecipitation, and in silico analysis. Dual
      targeting of Her2 and TrkB was analyzed using clinically utilized treatments.
      RESULTS: We observed that patient tissues and cell lines derived from Her2+ human
      BBM displayed increased activation of TrkB, a neurotrophin receptor. BDNF, an
      extracellular neurotrophin, with roles in neuronal maturation and homeostasis,
      specifically binds to TrkB. TrkB knockdown in breast cancer cells led to
      decreased frequency and growth of brain metastasis in animal models, suggesting
      that circulating breast cancer cells entering the brain may take advantage of
      paracrine BDNF-TrkB signaling for colonization. In addition, we investigated a
      possible interaction between TrkB and Her2 receptors on brain metastatic breast
      cancer cells, and found that BDNF phosphorylated both its cognate TrkB receptor
      and the Her2 receptor in brain metastatic breast cancer cells. CONCLUSION:
      Collectively, our findings suggest that heterodimerization of Her2 and TrkB
      receptors gives breast cancer cells a survival advantage in the brain and that
      dual inhibition of these receptors may hold therapeutic potential.

PMID- 28446207
TI  - Memory is preserved in older adults taking AT1 receptor blockers.
AB  - BACKGROUND: Prior work suggests that some but not all antihypertensive treatments
      may benefit cognition and risk for Alzheimer's disease, independent of stroke.
      Angiotensin II receptor blockers (ARBs) have been highlighted as one
      antihypertensive drug class that may confer greatest benefit. METHODS: The
      participants comprised 1626 nondemented adults, aged 55-91 years, recruited from
      Alzheimer's Disease Neuroimaging Initiative sites. Three groups were compared:
      ARB users (HTN-ARBs), other antihypertensive drug users (HTN-Other), and
      normotensives. In post hoc analyses, we also examined (1) users of ARBs and
      angiotensin-converting enzyme inhibitors (ACEIs), (2) users of blood-brain
      barrier (BBB)-crossing ARBs and users of non-BBB-crossing ARBs, and (3) users of
      BBB-crossing ARBs and ACEIs (BBB crossers) and users of non-BBB-crossing ARBs and
      ACEIs (BBB noncrossers). Groups were compared regarding cognition and magnetic
      resonance imaging measures of brain volume and white matter hyperintensities
      (WMH), using analysis of covariance and multilevel models. RESULTS: At baseline,
      the HTN-Other group performed worse than normotensives on Rey Auditory Verbal
      Learning Test (RAVLT) Immediate Recall (p = 0.002), Delayed Recall (p < 0.001),
      Recognition Memory (p = 0.001), and Trails A (p < 0.001) and B (p = 0.01). ARB
      users performed better than the HTN-Other group on Recognition Memory (p = 0.04)
      and worse than normotensives on Trails A (p = 0.04). The HTN-Other group
      performed worse than normotensives on Logical Memory Immediate (p = 0.02) and
      Delayed Recall over the 3-year follow-up (p = 0.007). Over the follow-up period,
      those taking BBB-crossing ARBs performed better than the HTN-Other group on AVLT
      Delayed Recall (p = 0.04), Logical Memory Immediate (p = 0.02), and Delayed
      Recall (p = 0.05). They also had fewer WMH than the HTN-Other group (p = 0.008)
      and those taking non-BBB-crossing ARBs (p = 0.05). There were no group
      differences in brain volume. Users of BBB-crossing medications (ARBs or ACEIs)
      showed better performance on AVLT Delayed Recall over time than all other groups,
      including normotensives (all p < 0.01), and had less WMH volume over time than
      the BBB noncrossers group (p = 0.03), although they had more WMH volume than
      normotensives (p = 0.01). The BBB noncrossers group performed worse than
      normotensives on Logical Memory Delayed Recall over time (p = 0.01), but the BBB
      crossers group was not significantly different (p = 0.13). CONCLUSIONS:
      Hypertensive participants demonstrated worse baseline memory and executive
      function, as well as greater memory decline, over the 3-year follow-up than
      normotensives, unless they were ARB users, who showed preserved memory compared
      with those taking other antihypertensive drugs. Users of BBB-crossing ARBs showed
      superior memory performance over time compared with other antihypertensive drug
      users and had less WMH volume. Users of BBB-crossing medications (ARBs or ACEIs)
      showed better list-learning memory performance over time than all other groups,
      including normotensives, and had less WMH volume over time than users of non-BBB
      crossing medications. These findings demonstrate that ARBs, especially those of
      the BBB-crossing variety, are associated with greater memory preservation and
      less WMH volume than other antihypertensive medications.

PMID- 28446208
TI  - Calgizzarin (S100A11): a novel inflammatory mediator associated with disease
      activity of rheumatoid arthritis.
AB  - BACKGROUND: Calgizzarin (S100A11) is a member of the S100 protein family that
      acts in different tumors by regulating a number of biologic functions. Recent
      data suggest its association with low-grade inflammation in osteoarthritis (OA).
      The aim of our study is to compare S100A11 expression in the synovial tissues,
      synovial fluid and serum of patients with rheumatoid arthritis (RA) and
      osteoarthritis (OA) and to characterize the potential association between S100A11
      and disease activity. METHODS: S100A11 protein expression was detected in
      synovial tissue from patients with RA (n = 6) and patients with OA (n = 6) by
      immunohistochemistry and immunofluorescence. Serum and synovial fluid S100A11
      levels were measured by ELISA in patients with RA (n = 40) and patients with OA
      (n = 34). Disease activity scores in 28 joints based on C-reactive protein (DAS28
      CRP) were used to assess disease activity. Cytokine content in peripheral blood
      mononuclear cells (PBMCs), synovial fibroblasts (SFs) and synovial fluid was
      analysed by ELISA, western blotting or cytometric bead array. RESULTS: S100A11
      expression was significantly up-regulated in the synovial lining and sublining
      layers (p < 0.01) and vessels (p < 0.05) of patients with RA compared to patients
      with OA, and was associated with fibroblasts and T cells. S100A11 was
      significantly increased in synovial fluid (p < 0.0001) but not in serum (p =
      0.158) from patients with RA compared to patients with OA when adjusted for age
      and sex. Synovial fluid S100A11 correlated with DAS28 (r = 0.350, p = 0.027),
      serum CRP (r = 0.463, p = 0.003), synovial fluid leukocyte count (r = 0.677, p <
      0.001), anti-cyclic citrullinated peptide antibodies (anti-CCP) (r = 0.424, p =
      0.006) and IL-6 (r = 0.578, p = 0.002) and IL-8 (r = 0.740, p < 0.001) in
      synovial fluid from patients with RA. PBMCs and SFs isolated from patients with
      RA synthesized and spontaneously secreted higher levels of S100A11 in comparison
      with PBMCs and SFs from patients with OA (p = 0.011 and 0.03, respectively).
      S100A11 stimulated the production of the pro-inflammatory cytokine IL-6 by PBMCs
      (p < 0.05) and SFs (p < 0.01). CONCLUSIONS: Our data provide the first evidence
      of S100A11 up-regulation and its association with inflammation and disease
      activity in patients with RA.

PMID- 28446209
TI  - Antipsychotic prescribing for Alzheimer's disease and related disorders in
      specialized settings from 2010 to 2014 in France: a repeated cross-sectional
      study.
AB  - BACKGROUND: Safety warnings from health authorities are currently intended to
      limit the use of antipsychotics (APs) in dementia-related conditions to treat
      neuropsychiatric symptoms, such as disturbing and/or delusional behaviors. The
      aim of this study is to investigate prevalence, correlates and trends of AP
      prescribing among people with dementia between 2010 and 2014 in the French
      population. METHODS: AP prescribing and associated factors among individuals with
      AD, mixed dementia and vascular dementia in the French National Alzheimer
      Database between 2010 and 2014 were analyzed using multivariate generalized
      estimating equations models (n = 199,549). RESULTS: In 2014, 7.7% of people with
      dementia were prescribed an AP. Compared with 2010 there was a 16% increase in AP
      use. Multivariate analysis showed a linear increase risk of prescription with an
      adjusted odds ratio (95% confidence interval) of 1.23 (1.17-1.30) in 2014
      compared with 2010. Factors associated with AP prescribing were male gender, more
      severe cognitive decline and living in long-term care facilities. Older age and
      higher education were protective toward AP prescribing. The type of dementia did
      not have any influence on AP prescribing. CONCLUSION: An increase in AP
      prescribing among individuals with dementia in French specialized settings over
      the last 5 years occurred despite safety warnings. This phenomenon suggests that
      alternative solutions for the management of behavioral and psychiatric symptoms
      in these populations are still urgently needed.

PMID- 28446210
TI  - Cognitive changes in alcohol-induced psychotic disorder.
AB  - AIMS: This study aimed to explore the neuro-cognitive deficits of alcohol-induced
      psychotic disorder as compared to the cognitive deficits of uncomplicated alcohol
      dependence. METHODS: Participants were recruited from the acute psychiatric
      admission wards of the Department of Psychiatry, University of Stellenbosch and
      Stikland and Tygerberg Academic Hospitals in the Western-Cape, South Africa.
      Participants who met DSM IV TR criteria (American Psychiatric Association.
      Diagnostic and statistical manual of mental disorders. American Psychiatric
      Association, Washington, DC, 2000) for Alcohol Dependence and for alcohol-induced
      psychotic disorder, respectively, were included. Participants who met criteria
      for another current DSM IV TR Axis I disorder were excluded. A structured
      interview was done prior to neuropsychological assessment to ascertain current
      mental state and to obtain relevant demographic detail and history.
      Neuropsychological assessments were performed and supervised by clinical
      psychologists at either Tygerberg or Stikland Hospital. RESULTS: The groups were
      matched demographically with similar period of abstinence prior to assessment.
      The alcohol-induced psychotic disorder group experienced first psychotic symptoms
      at age 35. The results reflected statistically significant differences on tasks
      measuring immediate memory; recall upon delay; exaggeration of memory difficulty
      and abstract thinking. CONCLUSION: This study concurs with earlier literature
      that some cognitive deficits are greater in alcohol-induced psychotic disorder
      compared to uncomplicated alcohol dependence.

PMID- 28446211
TI  - Spontaneous migraine attack causes alterations in default mode network
      connectivity: a resting-state fMRI case report.
AB  - BACKGROUND: Although migraine is one of the most investigated neurologic
      disorders, we do not have a perfect neuroimaging biomarker for its
      pathophysiology. One option to improve our knowledge is to study resting-state
      functional connectivity in and out of headache pain. However, our understanding
      of the functional connectivity changes during spontaneous migraine attack is
      partial and incomplete. CASE PRESENTATION: Using resting-state functional
      magnetic resonance imaging we assessed a 24-year old woman affected by migraine
      without aura at two different times: during a spontaneous migraine attack and in
      interictal phase. Seed-to-voxel whole brain analysis was carried out using the
      posterior cingulate cortex as a seed, representing the default mode network
      (DMN). Our results showed decreased intrinsic connectivity within core regions of
      the DMN with an exception of a subsystem including the dorsal medial and superior
      frontal gyri, and the mid-temporal gyrus which is responsible for pain
      interpretation and control. In addition, increased connectivity between the DMN
      and pain and specific migraine-related areas, such as the pons and hypothalamus,
      developed during the spontaneous migraine attack. CONCLUSION: Our preliminary
      results provide further support for the hypothesis that alterations of the DMN
      functional connectivity during migraine headache may lead to maladaptive top-down
      modulation of migraine pain-related areas which might be a specific biomarker for
      migraine.

PMID- 28446212
TI  - Doctors' preferences in de-escalating DMARDs in rheumatoid arthritis: a discrete
      choice experiment.
AB  - BACKGROUND: Current guidelines suggest reduction of DMARDs can be considered in
      RA patients in remission. Objectives were (1) to estimate the relative importance
      of patient characteristics rheumatologists consider in their decision to de
      escalate (2) to assess whether heterogeneity exists among rheumatologists with
      respect to de-escalation and (3) to identify the preferred de-escalation
      strategy. METHODS: A discrete choice experiment (DCE) was conducted. All
      rheumatologists and trainees in The Netherlands were invited to participate. A
      conditional logit model was estimated to assess overall preference for de
      escalation and its determinants. Heterogeneity was estimated by latent class
      analysis. RESULTS: The DCE questionnaire was completed by 156 doctors. This
      questionnaire was constructed using the results of semi-structured interviews
      with 12 rheumatologists that identified five patient characteristics relevant for
      de-escalation: number of swollen joints (SJC), presence of DAS remission/low
      disease activity (LDA), patient history, duration of remission/LDA and patient
      willingness to de-escalate DMARDs. Overall SJC and patient history were most
      important. Latent class analysis revealed five subgroups of doctors, showing
      differences regarding willingness to de-escalate and relative importance of
      patient characteristics. De-escalation of the TNF inhibitor rather than
      methotrexate first was the most preferred strategy. CONCLUSIONS: Rheumatologists
      are not uniform in their decision on whom to de-escalate. Differences emerged in
      which characteristics they traded off resulting in five subgroups: those that
      taper (1) always, (2) in absence of swollen joints, (3) in absence of swollen
      joints and presence of favorable patient history, (4) in DAS remission and
      favorable patient history, and (5) taking into account all factors.

PMID- 28446213
TI  - Manifesto: towards a clinically-oriented psychometrics.
AB  - BACKGROUND: New technologies to collect patient - reported outcomes have
      substantially solved the challenge of integrating a questionnaire in a busy
      clinical practice. At Memorial Sloan Kettering, we have been collecting patient
      reported outcomes electronically for many years. Our experience confirms the
      predicted benefits of obtaining patient reported outcomes but has also raised
      serious concerns about whether instruments developed for the research setting are
      appropriate for routine clinical use. DISCUSSION: We summarize four principles
      for a clinically - relevant psychometrics. First, minimize patient burden: the
      use of a large number of items for a single domain may be of interest for
      research but additional items have little clinical utility. Secondly, use
      simplified language: patients who do not have good language skills are typically
      excluded from research studies but will nonetheless present in clinical practice.
      Third, avoid dumb questions: many questionnaire items are inappropriate when
      applied to a more general population. Fourth, what works for the group may not
      work for the individual: group level statistics used to validate survey
      instruments can obscure problems when applied to a subgroup of patients.
      CONCLUSION: There is a need for a clinically-oriented psychometrics to help
      design, test, and evaluate questionnaires that would be used in routine practice.
      Developing statistical methods to optimize questionnaires will be highly
      challenging but needed to bring the potential of patient reported outcomes into
      widespread clinical use.

PMID- 28446215
TI  - Erratum to: Influence of Pokemon Go on physical activity levels of university
      players: a cross-sectional study.

PMID- 28446214
TI  - Epidemiological role of dogs since the human leishmaniosis outbreak in Madrid.
AB  - BACKGROUND: Canine leishmaniosis (CanL) has been in the spotlight since the 2009
      outbreak of human leishmaniosis in Madrid. In the framework of the Leishmaniosis
      Surveillance Programme set up in Madrid, this study examines Leishmania-specific
      seroprevalences in stray dogs for the outbreak area and rest of the Madrid region
      over the period spanning from the outbreak to the present (2009-2016). These data
      are of interest because stray dogs could be sentinels for disease surveillance in
      endemic areas. Since 2011, we have also been monitoring owned dogs in the
      outbreak area. METHODS: Over the study period, Leishmania infantum seroprevalence
      was determined in 2,123 stray dogs from the outbreak and non-outbreak areas. A
      serological study was also performed for owned dogs in the outbreak area: high
      risk dogs such as hunting or farm dogs (n = 1,722) and pets (n = 1372). All dogs
      were examined and blood was collected. The variables recorded for each animal
      were: breed, age, sex, and clinical history indicating if the animal was healthy
      or clinically suspected of having any disease, and if they showed a clinical
      picture compatible with CanL. RESULTS: Seroprevalences of L. infantum in stray
      dogs were similar in the two areas examined: 4.7% (20 out of 346) in the outbreak
      area and 5.4% (96 out of 1,777) in the remaining Madrid region (chi 2 = 0.080, P
      = 0.777). A significant association was found between seroprevalence and age (z =
      -6.319; P < 0.001). Seroprevalence in owned dogs in the outbreak area was 2.1% in
      high-risk dogs (37 out of 1,722) and 1.2% in pets (17 out of 1,372) (chi 2 =
      3.561, P = 0.0591). CONCLUSIONS: Both stray and owned dogs do not seem to play an
      important role in maintaining the transmission cycle of L. infantum in the Madrid
      outbreak area. The stable seroprevalence of infection observed in sentinel dogs
      suggests the good clinical management and prevention of CanL by local
      practitioners in owned dogs.

PMID- 28446216
TI  - The effect of adipose tissue-derived stem cells in a middle cerebral artery
      occlusion stroke model depends on their engraftment rate.
AB  - BACKGROUND: In the field of experimental stem cell therapy, intra-arterial (IA)
      delivery yields the best results concerning, for example, migrated cell number at
      the targeted site. However, IA application also appears to be associated with
      increased mortality rates and infarction. Since many rodent studies systemically
      apply 1 * 106 cells, this could also be a consequence of engrafted cell number.
      The aim of this study was therefore to investigate the effect of different doses
      of adipose tissue-derived stem cells (ASCs) on engraftment rates and stroke
      outcome measured in vivo using 9.4-T high-field magnetic resonance imaging (MRI).
      METHODS: Male Wistar rats (n = 43) underwent a middle cerebral artery occlusion
      (MCAo) for 45 or 90 min, followed by IA delivery of either saline or 1 * 106, 3 *
      105, or 5 * 104 ASCs pre-labelled with very small superparamagnetic iron oxide
      particles (VSOPs). MRI (9.4-T) analysis was performed 48 h and 9 days post-MCAo.
      Lesion volumes were assessed by analysis of T2-weighted images and cell signal
      tracking showing cell engraftment and active cell migration by an improved T2*
      analysis. RESULTS: The ASC-derived signal intensity increased in the affected
      hemisphere 48 h post MCAo with injected cell number (p < 0.05). The analysis of
      stroke volumes revealed an increased infarction after injection of 1 * 106 ASCs
      compared to controls or application of 5 * 104 ASCs (p < 0.05). At 9 days post
      MCAo, injection of 3 * 105 ASCs resulted in reduced infarct volumes (p < 0.05).
      Correspondingly, MRI analysis revealed no changes in cell numbers between both
      MRI examinations but showed active ASC migration to the site of infarction.
      CONCLUSION: Our results confirm that IA injection is an efficient way of
      targeting damaged brain tissue but its usefulness strongly depends on the right
      dose of delivered stem cells since this factor has a strong influence on
      migration rate and infarct volume, with better results for doses below 1 * 106
      cells. Future challenges will include the determination of therapeutic doses for
      best cellular engraftment and stroke outcome.

PMID- 28446217
TI  - Proximal methylation features associated with nonrandom changes in gene body
      methylation.
AB  - BACKGROUND: Gene body methylation at CG dinucleotides is a widely conserved
      feature of methylated genomes but remains poorly understood. The Arabidopsis
      thaliana strain Cvi has depleted gene body methylation relative to the reference
      strain Col. Here, we leverage this natural epigenetic difference to investigate
      gene body methylation stability. RESULTS: Recombinant inbred lines derived from
      Col and Cvi were used to examine the transmission of distinct gene body
      methylation states. The vast majority of genic CG methylation patterns are
      faithfully transmitted over nine generations according to parental genotype, with
      only 1-4% of CGs either losing or gaining methylation relative to the parent.
      Genic CGs that fail to maintain the parental methylation state are shared among
      independent lines, suggesting that these are not random occurrences. We use a
      logistic regression framework to identify features that best predict sites that
      fail to maintain parental methylation state. Intermediate levels of CG
      methylation around a dynamic CG site and high methylation variability across many
      A. thaliana strains at that site are the strongest predictors. These data suggest
      that the dynamic CGs we identify are not specific to the Col-Cvi recombinant
      inbred lines but have an epigenetic state that is inherently less stable within
      the A. thaliana species. Extending this, variably methylated genic CGs in maize
      and Brachypodium distachyon are also associated with intermediate local CG
      methylation. CONCLUSIONS: These results provide new insights into the features
      determining the inheritance of gene body methylation and demonstrate that two
      different methylation equilibria can be maintained within single individuals.

PMID- 28446218
TI  - Increased galectin-3 may serve as a serologic signature of pre-rheumatoid
      arthritis while markers of synovitis and cartilage do not differ between early
      undifferentiated arthritis subsets.
AB  - BACKGROUND: Undifferentiated arthritis (UA) is a label applied to patients with
      joint complaints which cannot be classified according to current criteria, which
      implies a need for precision diagnostic technologies. We studied serum galectin
      3, a proinflammatory mediator, and seromarkers of structural joint elements in
      patients with early, UA and their associations with disease profile and
      biochemical and imaging findings. METHODS: One hundred and eleven UA patients
      were followed-up for at least 12 months and reclassified according to appropriate
      criteria (TUDAR). At baseline, demographics and laboratory and clinical disease
      measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion,
      and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen
      N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage
      formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings,
      were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating
      characteristic (ROC) curve analysis was carried out to assess the discriminant
      capacity of galectin-3 against arthritis subsets. RESULTS: Galectin-3 was
      increased in pre-rheumatoid arthritis (RA) (4.6 MUg/l, interquartile range (IQR)
      3.8-5.5) versus non-RA (4.0 MUg/l, IQR 3.1-4.9; p = 0.03) and controls (3.8
      MUg/l, IQR 3.0-4.8; p = 0.009). PIIANP was equally depressed in either subset (p
      < 0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls.
      In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema
      score, while PIIANP correlated with the MRI erosion score, and HYA with the
      synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3
      discriminated well between pre-RA and non-RA with univariate area under the curve
      (AUC) of 0.64 (95% confidence interval (CI) 0.53-0.76) while AUC for galectin-3 +
      anti-CCP increased to 0.71 (95% CI 0.59-0.83). CONCLUSIONS: Galectin-3 in serum
      was increased in patients with early UA of pre-RA origin. Cartilage remodeling
      assessed by PIIANP was diminished in UA irrespective of subsequent clinical
      differentiation, while HYA did not differ from controls. ROC analysis showed a
      potential for galectin-3 to discriminate between pre-RA and non-RA. TRIAL
      REGISTRATION: KF 11 315829. Registered 25 July 2006.

PMID- 28446219
TI  - The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an
      evidence review.
AB  - BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a rapidly progressive, lethal
      neuromuscular disorder, present from birth, which occurs almost exclusively in
      males. We have reviewed contemporary evidence of burden, epidemiology, illness
      costs and treatment patterns of DMD. This systematic review adhered to published
      methods with information also sought from the web and contacting registries.
      Searches were carried out from 2005 to June 2015. The population of interest was
      individuals with clearly defined DMD or their carers. RESULTS: Nine thousand
      eight hundred fifty titles were retrieved from searches. Fifty-eight studies were
      reviewed with three assessed as high, 33 as medium and 22 as low quality. We
      found two studies reporting birth and four reporting point prevalence, three
      reporting mortality, 41 reporting severity and/or progression, 18 reporting
      treatment patterns, 12 reporting quality of life, two reporting utility measures,
      three reporting costs of illness and three treatment guidelines. Birth prevalence
      ranged from 15.9 to 19.5 per 100,000 live births. Point prevalence per 100,000
      males was for France, USA, UK and Canada, 10.9, 1.9, 2.2 and 6.1 respectively. A
      study of adult DMD patients at a centre in France found median survival for those
      born between 1970 and 1994 was 40.95 years compared to 25.77 years for those born
      between 1955 and 1969. Loss of ambulation occurred at a median age of 12 and
      ventilation starts at about 20 years. There was international variation in use of
      corticosteroids, scoliosis surgery, ventilation and physiotherapy. The economic
      cost of DMD climbs dramatically with disease progression - rising as much as 5.7
      fold from the early ambulatory phase to the non-ambulatory phase in Germany.
      CONCLUSIONS: This is the first systematic review of treatment, progression,
      severity and quality of life in DMD. It also provides the most recent description
      of the burden, epidemiology, illness costs and treatment patterns in DMD. There
      are evidence gaps, particularly in prevalence and mortality. People with DMD seem
      to be living longer, possibly due to corticosteroid use, cardiac medical
      management and ventilation. Future research should incorporate registry data to
      improve comparability across time and between countries and to investigate the
      quality of life impact as the condition progresses.

PMID- 28446220
TI  - SCALE: modeling allele-specific gene expression by single-cell RNA sequencing.
AB  - Allele-specific expression is traditionally studied by bulk RNA sequencing, which
      measures average expression across cells. Single-cell RNA sequencing allows the
      comparison of expression distribution between the two alleles of a diploid
      organism and the characterization of allele-specific bursting. Here, we propose
      SCALE to analyze genome-wide allele-specific bursting, with adjustment of
      technical variability. SCALE detects genes exhibiting allelic differences in
      bursting parameters and genes whose alleles burst non-independently. We apply
      SCALE to mouse blastocyst and human fibroblast cells and find that cis control in
      gene expression overwhelmingly manifests as differences in burst frequency.

PMID- 28446221
TI  - Effectiveness of three commonly used transition phase diets in the inpatient
      management of children with severe acute malnutrition: a pilot randomized
      controlled trial in Malawi.
AB  - BACKGROUND: The case fatality rate of severely malnourished children during
      inpatient treatment is high and mortality is often associated with diarrhea. As
      intestinal carbohydrate absorption is impaired in severe acute malnutrition
      (SAM), differences in dietary formulations during nutritional rehabilitation
      could lead to the development of osmotic diarrhea and subsequently hypovolemia
      and death. We compared three dietary strategies commonly used during the
      transition of severely malnourished children to higher caloric feeds, i.e., F100
      milk (F100), Ready-to-Use Therapeutic Food (RUTF) and RUTF supplemented with F75
      milk (RUTF + F75). METHODS: In this open-label pilot randomized controlled trial,
      74 Malawian children with SAM aged 6-60 months, were assigned to either F100,
      RUTF or RUTF + F75. Our primary endpoint was the presence of low fecal pH (pH <=
      5.5) measured in stool collected 3 days after the transition phase diets were
      introduced. Secondary outcomes were duration of hospital stay, diarrhea and other
      clinical outcomes. Chi-square test, two-way analysis of variance and logistic
      regression were conducted and, when appropriate, age, sex and initial weight for
      height Z-scores were included as covariates. RESULTS: The proportion of children
      with acidic stool (pH <=5.5) did not significantly differ between groups before
      discharge with 30, 33 and 23% for F100, RUTF and RUTF + F75, respectively. Mean
      duration of stay after transitioning was 7.0 days (SD 3.4) with no differences
      between the three feeding strategies. Diarrhea was present upon admission in 33%
      of patients and was significantly higher (48%) during the transition phase (p <
      0.05). There was no significant difference in mortality (n = 6) between diets
      during the transition phase nor were there any differences in other secondary
      outcomes. CONCLUSIONS: This pilot trial does not demonstrate that a particular
      transition phase diet is significantly better or worse since biochemical and
      clinical outcomes in children with SAM did not differ. However, larger and more
      tightly controlled efficacy studies are needed to confirm these findings. TRIAL
      REGISTRATION: ISRCTN13916953 Registered: 14 January 2013.

PMID- 28446222
TI  - Effect of quantity and intensity of pulsed light on human non-visual
      physiological responses.
AB  - BACKGROUND: Exposure to pulsed light results in non-visual physiological
      responses in humans. The present study aims to investigate whether such non
      visual effects are influenced to a greater extent by the intensity of lighting or
      by the power (quantity) of lighting. METHODS: >Twelve healthy young male
      participants (23 +/- 0.3 years, 21-24 age range) were recruited for the present
      study. Participants were exposed to light of varying levels of intensity and
      quantity whose frequency was held constant across the conditions, which consisted
      of exposure to blue (different intensity, constant quantity) and white (constant
      intensity, different quantity) LEDs. Pupillary constriction, electroencephalogram
      (EEG) alpha band ratio, subjective sleepiness, concentration and perception of
      blueness were measured. RESULTS: Pupillary constriction and subjective
      concentration were significantly greater under the high-intensity and short pulse
      width (HS) condition than under the low-intensity and long pulse width (LL)
      conditions at three time points during exposure to high-intensity light. However,
      no significant differences were observed among the results at the three time
      points during exposure to different quantities of pulsed light. CONCLUSIONS: The
      results of the present study indicate that non-visual influences of pulsed light
      on physiological function are mainly determined not by the quantity but by the
      intensity of the emitted light, with relatively higher levels of intensity
      producing more significant physiological changes, suggesting potent excitation of
      intrinsically photosensitive retinal ganglion cells.

PMID- 28446224
TI  - Immunosuppressive capacity of mesenchymal stem cells correlates with metabolic
      activity and can be enhanced by valproic acid.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have entered the clinic as an Advanced
      Therapy Medicinal Product and are currently evaluated in a wide range of studies
      for tissue regeneration or in autoimmune disorders. Various efforts have been
      made to standardize and optimize expansion and manufacturing processes, but until
      now reliable potency assays for the final MSC product are lacking. Because recent
      findings suggest superior therapeutic efficacy of freshly administered MSCs in
      comparison with frozen cells, we sought to correlate the T-cell suppressive
      capacity of MSCs with their metabolic activity. METHODS: Human MSCs were obtained
      from patients' bone fragments and were employed in coculture with peripheral
      blood mononuclear cells (PBMCs) in an allogeneic T-cell proliferation assay to
      measure immunosuppressive function. Metabolic activity of MSCs was measured in
      real time in terms of aerobic glycolysis quantified by the extracellular
      acidification rate and mitochondrial respiration quantified by the oxygen
      consumption rate. RESULTS: We show that MSC-induced suppression of T-cell
      proliferation was highly dependent on individual healthy donors' lymphocytes.
      Moreover, coculture with PBMCs increased the glycolytic and respiratory activity
      of MSCs considerably in a PBMC donor-dependent manner. The twofold to threefold
      enhancement of cell metabolism was accompanied by higher T-cell suppressive
      capacities of MSCs. The cryoprotectant dimethyl sulfoxide decreased metabolic and
      immunosuppressive performances of MSCs while valproic acid (VPA) increased their
      glycolytic, respiratory and T-cell suppressive capacity. CONCLUSIONS: Functional
      fitness of MSCs can be determined by measuring metabolic activity and can be
      enhanced by exposure to VPA. Pretesting the increment of metabolic activity upon
      interaction of donor MSCs with patient T-cells provides a rational approach for
      an individualized potency assay prior to MSC therapy.

PMID- 28446223
TI  - The effectiveness and cost-effectiveness of a mindfulness training programme in
      schools compared with normal school provision (MYRIAD): study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Mindfulness-based approaches for adults are effective at enhancing
      mental health, but few controlled trials have evaluated their effectiveness or
      cost-effectiveness for young people. The primary aim of this trial is to evaluate
      the effectiveness and cost-effectiveness of a mindfulness training (MT) programme
      to enhance mental health, wellbeing and social-emotional behavioural functioning
      in adolescence. METHODS/DESIGN: To address this aim, the design will be a
      superiority, cluster randomised controlled, parallel-group trial in which schools
      offering social and emotional provision in line with good practice (Formby et
      al., Personal, Social, Health and Economic (PSHE) Education: A mapping study of
      the prevalent models of delivery and their effectiveness, 2010; OFSTED, Not Yet
      Good Enough: Personal, Social, Health and Economic Education in schools, 2013)
      will be randomised to either continue this provision (control) or include MT in
      this provision (intervention). The study will recruit and randomise 76 schools
      (clusters) and 5700 school students aged 12 to 14 years, followed up for 2 years.
      DISCUSSION: The study will contribute to establishing if MT is an effective and
      cost-effective approach to promoting mental health in adolescence. TRIALS
      REGISTRATION: International Standard Randomised Controlled Trials, identifier:
      ISRCTN86619085 . Registered on 3 June 2016.

PMID- 28446225
TI  - The crosstalk between vascular MSCs and inflammatory mediators determines the pro
      calcific remodelling of human atherosclerotic aneurysm.
AB  - BACKGROUND: Human mesenchymal stem cells (MSCs) possess well-known reparative
      abilities, but any defect of the immunomodulatory activity and/or the
      differentiation process may determine the development of human diseases,
      including those affecting the vascular wall. MSCs residing within the human
      aortic wall represent a potential cell mediator of atherosclerotic aneurysm
      development. METHODS: MSCs isolated from healthy and aneurysm aortas were
      characterized by flow cytometer and tested for differentiation properties.
      Healthy aorta (ha)-MSCs were then subjected to inflammatory stimuli to evaluate
      the microenvironmental impact on their function and involvement in vascular
      remodelling. RESULTS: Abdominal aortic aneurysm (AAA)-MSCs were isolated from
      calcified and inflamed aortas of 12 patients with high serum levels of MMP-9
      protein. AAA-MSCs expressed typical mesenchymal markers and, in line with the
      histological analysis, elevated levels of OPN, an osteogenic marker also involved
      in vascular remodelling. AAA-MSCs were highly osteogenic and underwent intense
      calcium deposition under proper stimulation; moreover, AAA-MSCs were able to
      differentiate into tubule-like structures in Matrigel, even if the lack of CD146
      and the reduced structural stability suggested an inefficient maturation process.
      We further demonstrated an association between osteogenesis and inflammation;
      indeed, ha-MSCs cultured with either cytokines (TNF-alpha, IL-1beta) or AAA-PBMCs
      showed increased expression of MMP-9 and osteogenic markers, to the detriment of
      the adipogenic regulator PPAR-gamma. Interestingly, the culture with inflammatory
      cells highly stimulated ha-MSCs towards the osteogenic commitment. CONCLUSIONS:
      AAA-MSCs displayed high osteogenic potential and pathological angiogenesis that
      represent crucial steps for AAA progression; we showed that the inflammatory
      process critically addresses human vascular MSCs towards a pathological
      behaviour, inducing vascular bone matrix deposition and remodelling. Inhibition
      of this pathway may represent a pharmacological approach against arterial
      calcification.

PMID- 28446226
TI  - Xenotransplantation of interferon-gamma-pretreated clumps of a human mesenchymal
      stem cell/extracellular matrix complex induces mouse calvarial bone regeneration.
AB  - BACKGROUND: Three-dimensional cultured clumps of a mesenchymal stem cell
      (MSC)/extracellular matrix (ECM) complex (C-MSC) consists of cells and self
      produced ECM. C-MSC can regulate the cellular function in vitro and induce
      successful bone regeneration using ECM as a cell scaffold. Potentiating the
      immunomodulatory capacity of C-MSCs, which can ameliorate the allo-specific
      immune response, may be helpful in developing beneficial "off-the-shelf" cell
      therapy for tissue regeneration. It is well reported that interferon (IFN)-gamma
      stimulates the immunosuppressive properties of MSC via upregulation of the
      immunomodulatory enzyme IDO. Therefore, the aim of this study was to investigate
      the effect of IFN-gamma on the immunomodulatory capacity of C-MSC in vitro and to
      test the bone regenerative activity of C-MSC or IFN-gamma-pretreated C-MSC (C
      MSCgamma) xenografts in a mice calvarial defect model. METHODS: Human bone marrow
      derived MSCs were seeded at a density of 2.0 * 105 cells/well into 24-well plates
      and cultured with growth medium supplemented with 50 MUg/mL L-ascorbic acid for 4
      days. To obtain C-MSC, confluent cells that had formed on the cellular sheet were
      scratched using a micropipette tip and were then torn off. The cellular sheet was
      rolled to make a round clump of cells. C-MSC was stimulated with IFN-gamma and
      IDO expression, immunosuppressive capacity, and immunophenotype were evaluated in
      vitro. Moreover, C-MSC or C-MSCgamma was xenotransplanted into immunocompetent or
      immunodeficient mice calvarial defect models without artificial scaffold,
      respectively. RESULTS: IFN-gamma stimulated IDO expression in C-MSC. C-MSCgamma,
      but not C-MSC, attenuated CD3/CD28-induced T cell proliferation and its
      suppressive effect was reversed by an IDO inhibitor. C-MSCgamma showed
      upregulation of HLA-DR expression, but its co-stimulatory molecule, CD86, was not
      detected. Xenotransplantation of C-MSCgamma into immunocompetent mice calvarial
      defect induced bone regeneration, whereas C-MSC xenograft failed and induced T
      cell infiltration in the grafted area. On the other hand, both C-MSC and C
      MSCgamma xenotransplantation into immunodeficient mice caused bone regeneration.
      CONCLUSIONS: Xenotransplantation of C-MSCgamma, which exerts immunomodulatory
      properties via the upregulation of IDO activity in vitro, may attenuate
      xenoreactive host immune response, and thereby induce bone regeneration in mice.
      Accordingly, C-MSCgamma may constitute a promising novel allograft cell therapy
      for bone regeneration.

PMID- 28446227
TI  - Pattern analysis of schistosomiasis prevalence by exploring predictive modeling
      in Jiangling County, Hubei Province, P.R. China.
AB  - BACKGROUND: The prevalence of schistosomiasis remains a key public health issue
      in China. Jiangling County in Hubei Province is a typical lake and marshland
      endemic area. The pattern analysis of schistosomiasis prevalence in Jiangling
      County is of significant importance for promoting schistosomiasis surveillance
      and control in the similar endemic areas. METHODS: The dataset was constructed
      based on the annual schistosomiasis surveillance as well the socio-economic data
      in Jiangling County covering the years from 2009 to 2013. A village clustering
      method modified from the K-mean algorithm was used to identify different types of
      endemic villages. For these identified village clusters, a matrix-based
      predictive model was developed by means of exploring the one-step backward
      temporal correlation inference algorithm aiming to estimate the predicative
      correlations of schistosomiasis prevalence among different years. Field sampling
      of faeces from domestic animals, as an indicator of potential schistosomiasis
      prevalence, was carried out and the results were used to validate the results of
      proposed models and methods. RESULTS: The prevalence of schistosomiasis in
      Jiangling County declined year by year. The total of 198 endemic villages in
      Jiangling County can be divided into four clusters with reference to the 5 years'
      occurrences of schistosomiasis in human, cattle and snail populations. For each
      identified village cluster, a predictive matrix was generated to characterize the
      relationships of schistosomiasis prevalence with the historic infection level as
      well as their associated impact factors. Furthermore, the results of sampling
      faeces from the front field agreed with the results of the identified clusters of
      endemic villages. CONCLUSION: The results of village clusters and the predictive
      matrix can be regard as the basis to conduct targeted measures for
      schistosomiasis surveillance and control. Furthermore, the proposed models and
      methods can be modified to investigate the schistosomiasis prevalence in other
      regions as well as be used for investigating other parasitic diseases.

PMID- 28446228
TI  - Antigenotoxic properties of Paliurus spina-christi Mill fruits and their active
      compounds.
AB  - BACKGROUND: Paliurus spina-christi Mill. (PS) fruits are widely used for
      different medical purposes in Turkey. Like in many medicinal herbs the studies
      concerning their activity, the activities of PS are also not well clarified. The
      aim of this study is to evaluate the antigenotoxicity of the compounds isolated
      and identified from the extracts of PS fruits. METHODS: The active compounds were
      separated, isolated, and determined by chromatographic methods and their
      structural elucidation was performed by Nuclear Magnetic Resonance (NMR) methods.
      The compounds were obtained from either ethyl acetate (EA) or n-butanol extracts.
      The cytotoxicities of the compounds using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and the antigenotoxic activities of the
      compounds using the alkaline single cell gel electrophoresis techniques (comet
      assay) were evaluated in Chinese hamster lung fibroblast (V79) cell lines.
      RESULTS: The isolated major compounds were identified as (+/-) catechins and
      gallocatechin from EA fraction and rutin from n-butanol fraction of PS fruits.
      Their chemical structures were identified by 1H-NMR, 13C-NMR, HMBC, and HMQC
      techniques. Half-maximal inhibitory concentration of catechins, gallocatechin,
      and rutin were found to be 734 MUg/mL, 220 MUg/mL, and 1004 MUg/mL, respectively.
      The methanolic extract of PS (1-100 MUg/mL) alone did not induce DNA single
      strand breaks while catechins (1-100 MUg/mL), gallocatechin (1-50 MUg/mL), and
      rutin (1-50 MUg/mL) significantly reduced H2O2-induced DNA damage. CONCLUSION: It
      has been suggested that PS fruits and their compounds catechins, gallocatechin
      and rutin may have beneficial effects in oxidative DNA damage. It seems that PS
      fruits may be used in protection of the disorders related to DNA damage.

PMID- 28446229
TI  - Expanding protection motivation theory: investigating an application to animal
      owners and emergency responders in bushfire emergencies.
AB  - BACKGROUND: Protection Motivation Theory (PMT) was developed by Rogers in 1975,
      to describe how individuals are motivated to react in a self-protective way
      towards a perceived health threat. Rogers expected the use of PMT to diversify
      over time, which has proved true over four decades. The purpose of this paper is
      to explore how PMT can be used and expanded to inform and improve public safety
      strategies in natural hazards. As global climate change impacts on the Australian
      environment, natural hazards seem to be increasing in scale and frequency, and
      Emergency Services' public education campaigns have necessarily escalated to keep
      pace with perceived public threat. Of concern, is that the awareness-preparedness
      gap in residents' survival plans is narrowing disproportionately slowly compared
      to the magnitude of resources applied to rectify this trend. Practical
      applications of adaptable social theory could be used to help resolve this
      dilemma. DISCUSSION: PMT has been used to describe human behaviour in
      individuals, families, and the parent-child unit. It has been applied to floods
      in Europe and wildfire and earthquake in the United States. This paper seeks to
      determine if an application of PMT can be useful for achieving other-directed
      human protection across a novel demographic spectrum in natural hazards,
      specifically, animal owners and emergency responders in bushfire emergencies.
      These groups could benefit from such an approach: owners to build and fortify
      their response- and self-efficacy, and to help translate knowledge into safer
      behaviour, and responders to gain a better understanding of a diverse demographic
      with animal ownership as its common denominator, and with whom they will be
      likely to engage in contemporary natural hazard management. Mutual collaboration
      between these groups could lead to a synergy of reciprocated response efficacy,
      and safer, less traumatic outcomes. Emergency services' community education
      programs have made significant progress over the last decade, but public safety
      remains suboptimal while the magnitude of the awareness-preparedness gap
      persists. This paper examines an expanded, other-directed application of PMT to
      expand and enhance safer mitigation and response behaviour strategies for
      communities threatened by bushfire, which may ultimately help save human life.

PMID- 28446230
TI  - Label retention and stem cell marker expression in the developing and adult
      prostate identifies basal and luminal epithelial stem cell subpopulations.
AB  - BACKGROUND: Prostate cancer is the second most frequent cancer among males
      worldwide, and most patients with metastatic disease eventually develop therapy
      resistant disease. Recent research has suggested the existence of cancer stem
      like cells, and that such cells are behind the therapy resistance and
      progression. METHODS: Here, we have taken advantage of the relatively quiescent
      nature of stem cells to identify the slow-cycling label-retaining stem cell (LRC)
      populations of the prostate gland. Mice were pulsed with bromodeoxyuridine (BrdU)
      during prostate organogenesis, and the LRC populations were then identified and
      characterized in 5-day-old and in 6-month-old adult animals using
      immunohistochemistry and immunofluorescence. RESULTS: Quantification of LRCs in
      the adult mouse prostate showed that epithelial LRCs were significantly more
      numerous in prostatic ducts (3.7 +/- 0.47% SD) when compared to the proximal (1.4
      +/- 0.83%) and distal epithelium (0.48 +/- 0.08%) of the secretory lobes. LRCs
      were identified in both the basal and epithelial cell layers of the prostate, and
      LRCs co-expressed several candidate stem cell markers in a developmental and
      duct/acini-specific manner, including Sca-1, TROP-2, CD133, CD44, c-kit, and the
      novel prostate progenitor marker cytokeratin-7. Importantly, a significant
      proportion of LRCs were localized in the luminal cell layer, the majority in
      ducts and the proximal prostate, that co-expressed high levels of androgen
      receptor in the adult prostate. CONCLUSIONS: Our results suggest that there are
      separate basal and luminal stem cell populations in the prostate, and they open
      up the possibility that androgen receptor-expressing luminal stem-like cells
      could function as cancer-initiating and relapse-responsible cells in prostate
      cancer.

PMID- 28446232
TI  - Continuous quality improvement interventions to improve long-term outcomes of
      antiretroviral therapy in women who initiated therapy during pregnancy or
      breastfeeding in the Democratic Republic of Congo: design of an open-label,
      parallel, group randomized trial.
AB  - BACKGROUND: Despite the rapid adoption of the World Health Organization's 2013
      guidelines, children continue to be infected with HIV perinatally because of sub
      optimal adherence to the continuum of HIV care in maternal and child health (MCH)
      clinics. To achieve the UNAIDS goal of eliminating mother-to-child HIV
      transmission, multiple, adaptive interventions need to be implemented to improve
      adherence to the HIV continuum. METHODS: The aim of this open label, parallel,
      group randomized trial is to evaluate the effectiveness of Continuous Quality
      Improvement (CQI) interventions implemented at facility and health district
      levels to improve retention in care and virological suppression through 24 months
      postpartum among pregnant and breastfeeding women receiving ART in MCH clinics in
      Kinshasa, Democratic Republic of Congo. Prior to randomization, the current
      monitoring and evaluation system will be strengthened to enable collection of
      high quality individual patient-level data necessary for timely indicators
      production and program outcomes monitoring to inform CQI interventions. Following
      randomization, in health districts randomized to CQI, quality improvement (QI)
      teams will be established at the district level and at MCH clinics level. For 18
      months, QI teams will be brought together quarterly to identify key bottlenecks
      in the care delivery system using data from the monitoring system, develop an
      action plan to address those bottlenecks, and implement the action plan at the
      level of their district or clinics. DISCUSSION: If proven to be effective, CQI as
      designed here, could be scaled up rapidly in resource-scarce settings to
      accelerate progress towards the goal of an AIDS free generation. TRIAL
      REGISTRATION: The protocol was retrospectively registered on February 7, 2017.
      ClinicalTrials.gov Identifier: NCT03048669 .

PMID- 28446231
TI  - Remote ischemic preconditioning differentially attenuates post-ischemic cardiac
      arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.
AB  - BACKGROUND: Sudden cardiac death (SCD), a leading cause of global mortality, most
      commonly arises from a substrate of cardiac ischemia, but requires an additional
      trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other
      DM-linked cardiovascular pathology such as coronary artery disease. We previously
      showed that remote liver ischemia preconditioning (RLIPC) is highly protective
      against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias
      and myocardial infarction, via induction of the cardioprotective RISK pathway,
      and specifically, inhibitory phosphorylation of GSK-3beta (Ser 9). METHODS: We
      evaluated the impact of acute streptozotocin-induced DM on coronary artery
      ligation IRI-linked ventricular arrhythmogenesis and RLIPC therapy in rats.
      RESULTS: Post-IRI arrhythmia induction was similar in nondiabetic and DM rats,
      but, unexpectedly, DM rats exhibited lower incidence of SCD during reperfusion
      (41 vs. 100%), suggesting uncontrolled hyperglycemia does not acutely predispose
      to SCD. RLIPC was highly effective in both nondiabetic and DM rats at reducing
      incidence and duration of, and increasing latency to, all classes of ventricular
      tachyarrhythmias. In contrast, atrioventricular block (AVB) was highly responsive
      to RLIPC in nondiabetic rats (incidence reduced from 72 to 18%) but unresponsive
      in DM rats. RISK pathway induction was similar in nondiabetic and DM rats, thus
      not explaining the DM-specific resistance of AVB to therapy. CONCLUSIONS: Our
      findings uncover important acute DM-specific differences in responsiveness to
      remote preconditioning for ventricular tachyarrhythmias versus AVB, which may
      have clinical significance given that AVB is a malignant arrhythmia twofold more
      common in human diabetics than nondiabetics, and correlated to plasma glucose
      levels >10 mmol/L.

PMID- 28446233
TI  - No impact of strongylid infections on the detection of Plasmodium spp. in faeces
      of western lowland gorillas and eastern chimpanzees.
AB  - BACKGROUND: Although a high genetic diversity of Plasmodium spp. circulating in
      great apes has been revealed recently due to non-invasive methods enabling
      detection in faecal samples, little is known about the actual mechanisms
      underlying the presence of Plasmodium DNA in faeces. Great apes are commonly
      infected by strongylid nematodes, including hookworms, which cause intestinal
      bleeding. The impact of strongylid infections on the detection of Plasmodium DNA
      in faeces was assessed in wild, western, lowland gorillas from Dzanga Sangha
      Protected Areas, Central African Republic and eastern chimpanzees from Kalinzu
      Forest Reserve, Uganda. METHODS: Fifty-one faecal samples from 22 habituated
      gorillas and 74 samples from 15 habituated chimpanzees were analysed using
      Cytochrome-b PCR assay and coprological methods. RESULTS: Overall, 26.4% of the
      analysed samples were positive for both Plasmodium spp. and strongylids. However,
      the results showed no significant impact of intensity of infections of
      strongylids on detection of Plasmodium DNA in gorilla and chimpanzee faeces.
      CONCLUSION: Bleeding caused by strongylid nematode Necator spp. cannot explain
      the presence of Plasmodium DNA in ape faeces.

PMID- 28446234
TI  - Retinal vessel diameters and reactivity in diabetes mellitus and/or
      cardiovascular disease.
AB  - BACKGROUND: Retinal vessel calibre and vascular dilation/constriction in response
      to flicker light provocation may provide a measure distinguishing patients
      suffering from diabetes mellitus and/or cardiovascular disease. METHODS: One
      hundred and sixteen age and sex matched patients with diabetes mellitus (DM),
      cardiovascular disease (CVD) and both DM and CVD (DM + CVD) underwent systemic
      and intraocular pressure measurements. Retinal vessel calibres were assessed
      using a validated computer-based program to compute central retinal artery and
      vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and
      constriction responses to flicker light provocation were assessed by continuous
      retinal vessel diameter recordings. Plasma endothelial markers von Willebrand
      factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. RESULTS:
      Retinal vessel calibres were comparable across groups but CRVE correlated
      significantly with disease duration in DM patients (r = 0.57, p < 0.001).
      Patients suffering DM only exhibited reduced arterial vasomotion at rest and
      reduced arterial constriction following flicker light induced vessel dilation
      compared to patients with CVD and those suffering both CVD + DM (p = 0.030).
      Patients suffering from CVD + DM exhibited significant differences between each
      flicker cycle in regards to arterial maximum constriction (p = 0.006) and time
      needed to reach arterial maximum dilation (p = 0.004), whereas the other two
      groups did not show such inconsistencies between individual flicker cycles. vWf
      was raised in CVD + DM compared to the other two groups (p <= 0.02), whilst sEsel
      was raised in CVD + DM compared to DM alone (p = 0.044). CONCLUSIONS: Dynamic
      retinal vascular calibres as obtained by continuous diameter measurements using
      flicker light provocation can reveal subtle differences between groups suffering
      from CVD with and without DM. This difference in reaction pattern and lack of
      arterial constriction in DM may provide a suitable marker to monitor progression.

PMID- 28446235
TI  - Differential expression of cell cycle and WNT pathway-related genes accounts for
      differences in the growth and differentiation potential of Wharton's jelly and
      bone marrow-derived mesenchymal stem cells.
AB  - BACKGROUND: In view of the current interest in exploring the clinical use of
      mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side
      comparison of the biological properties of MSCs isolated from the Wharton's jelly
      (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs,
      the most extensively studied MSC population. METHODS: MSCs were isolated and
      expanded from BM aspirates of hematologically healthy donors (n = 18) and from
      the WJ of full-term neonates (n = 18). We evaluated, in parallel experiments, the
      MSC immunophenotypic, survival and senescence characteristics as well as their
      proliferative potential and cell cycle distribution. We also assessed the
      expression of genes associated with the WNT- and cell cycle-signaling pathway and
      we performed karyotypic analysis through passages to evaluate the MSC genomic
      stability. The hematopoiesis-supporting capacity of MSCs from both sources was
      investigated by evaluating the clonogenic cells in the non-adherent fraction of
      MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by
      measuring the hematopoietic cytokines levels in MSC culture supernatants.
      Finally, we evaluated the ability of MSCs to differentiate into adipocytes and
      osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the
      differentiation potential of WJ-MSCs. RESULTS: Both ex vivo-expanded MSC
      populations showed similar morphologic, immunophenotypic, survival and senescence
      characteristics and acquired genomic alterations at low frequency during
      passages. WJ-MSCs exhibited higher proliferative potential, possibly due to
      upregulation of genes that stimulate cell proliferation along with downregulation
      of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage
      priming and differentiation capacity toward osteocytes and adipocytes, compared
      to BM-MSCs. This finding was associated with differential expression of molecules
      related to WNT signaling, including WISP1 and sFRP4, the respective role of which
      in the differentiation potential of WJ-MSCs was specifically investigated.
      Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4
      resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs
      exhibited inferior hematopoiesis-supporting potential probably due to reduced
      production of stromal cell-Derived Factor-1alpha, compared to BM-MSCs.
      CONCLUSIONS: Overall, these data are anticipated to contribute to the better
      characterization of WJ-MSCs and BM-MSCs for potential clinical applications.

PMID- 28446237
TI  - Oral impacts on quality of life and problem-oriented attendance among South East
      London adults.
AB  - BACKGROUND: Dental care seeking behaviour is often driven by symptoms. The value
      of oral health related quality of life (OHRQoL) measures to predict utilisation
      of dental services is unknown. This study aims to explore the association between
      OHRQoL and problem-oriented dental attendance among adults. METHODS: We analysed
      cross-sectional data for 705 adults, aged 16 years and above, living in three
      boroughs of Inner South East London. Data were collected during structured
      interviews at home. The short form of the Oral Health Impact Profile (OHIP-14)
      was used to assess the frequency of oral impacts on daily life in the last year.
      Problem-oriented attendance was defined based on time elapsed since last visit
      (last 6 months) and reason for that visit (trouble with teeth). The association
      between OHIP-14 (total and domain) scores and problem-oriented attendance was
      tested in logistic regression models adjusting for participants' sociodemographic
      characteristics. RESULTS: Problem-oriented attenders had a higher OHIP-14 total
      score than regular attenders (6.73 and 3.73, respectively). In regression models,
      there was a positive association between OHIP-14 total score and problem-oriented
      attendance. The odds of visiting the dentist for trouble with teeth were 1.07
      greater (95% Confidence Interval: 1.04-1.10) per unit increase in the OHIP-14
      total score, after adjustment for participants' sociodemographic characteristics.
      In subsequent analysis by OHIP-14 domains, greater scores in all domains but
      handicap were significantly associated with problem-oriented attendance.
      CONCLUSION: This study shows that oral impacts on quality of life are associated
      with recent problem-oriented dental attendance among London adults. Six of the
      seven domains in the OHIP-14 questionnaire were also associated with dental
      visits for trouble with teeth.

PMID- 28446238
TI  - Changing ethnic inequalities in mortality in New Zealand over 30 years: linked
      cohort studies with 68.9 million person-years of follow-up.
AB  - BACKGROUND: Internationally, ethnic inequalities in mortality within countries
      are increasingly recognized as a public health concern. But few countries have
      data to monitor such inequalities. We aimed to provide a detailed description of
      ethnic inequalities (Maori [indigenous], Pacific, and European/Other) in
      mortality for a country with high quality ethnicity data, using both standard and
      novel visualization methods. METHODS: Cohort studies of the entire New Zealand
      population were conducted, using probabilistically-linked Census and mortality
      data from 1981 to 2011 (68.9 million person years). Absolute (standardized rate
      difference) and relative (standardized rate ratio) inequalities were calculated,
      in 1-74-year-olds, for Maori and Pacific peoples in comparison to European/Other.
      RESULTS: All-cause mortality rates were highest for Maori, followed by Pacific
      peoples then European/Other, and declined in all three ethnic groups over time.
      Pacific peoples experienced the slowest annual percentage fall in mortality
      rates, then Maori, with European/Other having the highest percentage falls -
      resulting in widening relative inequalities. Absolute inequalities, however, for
      both Maori and Pacific males compared to European/Other have been falling since
      1996. But for females, only Maori absolute inequalities (compared with
      European/Other) have been falling. Regarding cause of death, cancer is becoming a
      more important contributor than cardiovascular disease (CVD) to absolute
      inequalities, especially for Maori females. CONCLUSIONS: We found declines in all
      cause mortality rates, over time, for each ethnic group of interest. Ethnic
      mortality inequalities are generally stable or even falling in absolute terms,
      but have increased on a relative scale. The drivers of these inequalities in
      mortality are transitioning over time, away from CVD to cancer and diabetes; such
      transitions are likely in other countries, and warrant further research. To
      address these inequalities, policymakers need to enhance prevention activities
      and health care delivery, but also support wider improvements in educational
      achievement and socioeconomic position for highest need populations.

PMID- 28446236
TI  - The malaria testing and treatment landscape in Benin.
AB  - BACKGROUND: Since 2004, artemisinin-based combination therapy (ACT) has been the
      first-line treatment for uncomplicated malaria in Benin. In 2016, a medicine
      outlet survey was implemented to investigate the availability, price, and market
      share of anti-malarial treatment and malaria diagnostics. Results provide a
      timely and important benchmark to measure future interventions aimed at
      increasing access to quality malaria case management services. METHODS: Between
      July 5th to August 6th 2016, a cross sectional, nationally-representative malaria
      outlet survey was conducted in Benin. A census of all public and private outlets
      with potential to distribute malaria testing and/or treatment was implemented
      among 30 clusters (arrondissements). Outlets were eligible for inclusion in the
      study if they met at least one of three study criteria: (1) one or more anti
      malarials reportedly in stock on the day of the survey; (2) one or more anti
      malarials reportedly in stock within the 3 months preceding the survey; and/or
      (3) provided malaria blood testing. An audit was completed for all anti
      malarials, malaria rapid diagnostic tests (RDT) and microscopy. RESULTS: 7260
      outlets with the potential to sell or distribute anti-malarials were included in
      the census and 2966 were eligible and interviewed. A total of 17,669 anti
      malarial and 494 RDT products were audited. Quality-assured ACT was available in
      95.0% of all screened public health facilities and 59.4% of community health
      workers (CHW), and availability of malaria blood testing was 94.7 and 68.4%
      respectively. Sulfadoxine-pyrimethamine (SP) was available in 73.9% of public
      health facilities and not found among CHWs. Among private-sector outlets stocking
      at least one anti-malarial, non-artemisinin therapies were most commonly
      available (94.0% of outlets) as compared to quality-assured ACT (36.1%). 31.3% of
      the ACTs were marked with a "green leaf" logo, suggesting leakage of a co-paid
      ACT into Benin's unsubsidized ACT market from another country. 78.5% of the anti
      malarials distributed were through the private sector, typically through general
      retailers (47.6% of all anti-malarial distribution). ACT comprised 44% of the
      private anti-malarial market share. Private-sector price of quality-assured ACT
      ($1.35) was three times more expensive than SP ($0.42) or chloroquine ($0.41).
      Non-artemisinin therapies were cited as the most effective treatment for
      uncomplicated malaria among general retailers and itinerant drug vendors.
      CONCLUSIONS: The ACTwatch data has shown the importance of the private sector in
      terms of access to malaria treatment for the majority of the population in Benin.
      These findings highlight the need for increased engagement with the private
      sector to improve malaria case management and an immediate need for a national
      ACT subsidy.

PMID- 28446239
TI  - Dasatinib + Gefitinib, a non platinum-based combination with enhanced growth
      inhibitory, anti-migratory and anti-invasive potency against human ovarian cancer
      cells.
AB  - BACKGROUND: Ovarian cancer is the leading cause of death for gynecological
      cancers and the 6th cause of women cancer death in developed countries. The late
      stage detection, the peritoneal dissemination and the acquisition of resistance
      against carboplatin are the main reasons to explain this poor prognosis and
      strengthen the need of alternative treatments to improve the management of
      ovarian cancer and/or to sensitize tumors to platinum salts. Epidermal growth
      factor receptor (EGFR), hepatocyte growth factor receptor (Met) and cellular Src
      kinase (c-Src) are crucial kinases implied in ovarian tumor growth, survival,
      invasion and resistance to carboplatin. Their expression is increased in advanced
      ovarian cancers and is correlated with poor prognosis. Despite a clear potential
      in inhibiting these proteins in ovarian cancer, as a single agent or in
      combination with a carboplatin treatment, we need to target kinases in tandem
      because of their capacity to trigger compensatory pathways that synergize to
      promote drug resistance. METHODS: Here we target EGFR, c-Src and Met individually
      or in combination with carboplatin, using Gefitinib, Dasatinib and Crizotinib
      respectively, in a panel of carboplatin-sensitive (OVCAR-3, IGROV-1 and A2780)
      and carboplatin-resistant cells (SKOV-3 and EFO-21). We studied the ability of
      the most potent combination to induce apoptosis, regulate migration, invasion and
      to modulate the activation of proliferation and survival proteins. RESULTS:
      Crizotinib, Dasatinib and Gefitinib, alone or in combination with carboplatin,
      showed a cell-specific cytotoxic synergy in ovarian cancer cells. The Dasatinib
      plus Gefitinib combination was synergistic in OVCAR-3, SKOV-3 and, in IGROV-1
      cells (high concentrations). This combination was unable to induce apoptosis but
      suppressed cell migration, invasion and the activation of EGFR, Erk, c-Src and
      Akt compared to single treatments. CONCLUSIONS: Combining carboplatin with kinase
      inhibitors lead to synergistic interactions in a cell-specific manner. Unlike
      platinum-based combinations, mixing Dasatinib with Gefitinib led to cytotoxic
      activity, inhibition of cell migration and invasion. Thus, the Dasatinib +
      Gefitinib combination presents anti-tumour properties that are superior to those
      of platinum-based combinations, indicating that it may well represent a promising
      new treatment modality to be tested in the clinic.

PMID- 28446241
TI  - Polyunsaturated fatty acid receptors, GPR40 and GPR120, are expressed in the
      hypothalamus and control energy homeostasis and inflammation.
AB  - BACKGROUND: The consumption of large amounts of dietary fats is one of the most
      important environmental factors contributing to the development of obesity and
      metabolic disorders. GPR120 and GPR40 are polyunsaturated fatty acid receptors
      that exert a number of systemic effects that are beneficial for metabolic and
      inflammatory diseases. Here, we evaluate the expression and potential role of
      hypothalamic GPR120 and GPR40 as targets for the treatment of obesity. METHODS:
      Male Swiss (6-weeks old), were fed with a high fat diet (HFD, 60% of kcal from
      fat) for 4 weeks. Next, mice underwent stereotaxic surgery to place an indwelling
      cannula into the right lateral ventricle. intracerebroventricular (icv)
      cannulated mice were treated twice a day for 6 days with 2.0 MUL saline or GPR40
      and GPR120 agonists: GW9508, TUG1197, or TUG905 (2.0 MUL, 1.0 mM). Food intake
      and body mass were measured during the treatment period. At the end of the
      experiment, the hypothalamus was collected for real-time PCR analysis. RESULTS:
      We show that both receptors are expressed in the hypothalamus; GPR120 is
      primarily present in microglia, whereas GPR40 is expressed in neurons. Upon
      intracerebroventricular treatment, GW9508, a non-specific agonist for both
      receptors, reduced energy efficiency and the expression of inflammatory genes in
      the hypothalamus. Reducing GPR120 hypothalamic expression using a lentivirus
      based approach resulted in the loss of the anti-inflammatory effect of GW9508 and
      increased energy efficiency. Intracerebroventricular treatment with the GPR120-
      and GPR40-specific agonists TUG1197 and TUG905, respectively, resulted in milder
      effects than those produced by GW9508. CONCLUSIONS: GPR120 and GPR40 act in
      concert in the hypothalamus to reduce energy efficiency and regulate the
      inflammation associated with obesity. The combined activation of both receptors
      in the hypothalamus results in better metabolic outcomes than the isolated
      activation of either receptor alone.

PMID- 28446240
TI  - Molecular mechanisms by which HERV-K Gag interferes with HIV-1 Gag assembly and
      particle infectivity.
AB  - BACKGROUND: Human endogenous retroviruses (HERVs), the remnants of ancient
      retroviral infections, constitute approximately 8% of human genomic DNA. Since
      HERV-K Gag expression is induced by HIV-1 Tat in T cells, induced HERV-K proteins
      could affect HIV-1 replication. Indeed, previously we showed that HERV-K Gag and
      HIV-1 Gag coassemble and that this appears to correlate with the effect of HERV-K
      Gag expression on HIV-1 particle release and its infectivity. We further showed
      that coassembly requires both MA and NC domains, which presumably serve as
      scaffolding for Gag via their abilities to bind membrane and RNA, respectively.
      Notably, however, despite possessing these abilities, MLV Gag failed to
      coassemble with HIV-1 Gag and did not affect assembly and infectivity of HIV-1
      particles. It is unclear how the specificity of coassembly is determined.
      RESULTS: Here, we showed that coexpression of HERV-K Gag with HIV-1 Gag changed
      size and morphology of progeny HIV-1 particles and severely diminished
      infectivity of such progeny viruses. We further compared HERV-K-MLV chimeric
      constructs to identify molecular determinants for coassembly specificity and for
      inhibition of HIV-1 release efficiency and infectivity. We found that the CA N
      terminal domain (NTD) of HERV-K Gag is important for the reduction of the HIV-1
      release efficiency, whereas both CA-NTD and major homology region of HERV-K Gag
      contribute to colocalization with HIV-1 Gag. Interestingly, these regions of HERV
      K Gag were not required for reduction of progeny HIV-1 infectivity. CONCLUSIONS:
      Our results showed that HERV-K Gag CA is important for reduction of HIV-1 release
      and infectivity but the different regions within CA are involved in the effects
      on the HIV-1 release and infectivity. Altogether, these findings revealed that
      HERV-K Gag interferes the HIV-1 replication by two distinct molecular mechanisms.

PMID- 28446242
TI  - Activity of distinct growth factor receptor network components in breast tumors
      uncovers two biologically relevant subtypes.
AB  - BACKGROUND: The growth factor receptor network (GFRN) plays a significant role in
      driving key oncogenic processes. However, assessment of global GFRN activity is
      challenging due to complex crosstalk among GFRN components, or pathways, and the
      inability to study complex signaling networks in patient tumors. Here, pathway
      specific genomic signatures were used to interrogate GFRN activity in breast
      tumors and the consequent phenotypic impact of GRFN activity patterns. METHODS:
      Novel pathway signatures were generated in human primary mammary epithelial cells
      by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS
      (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection and
      InteGratioN (ASSIGN) was used to estimate pathway activity for GFRN components in
      1119 breast tumors from The Cancer Genome Atlas (TCGA) and across 55 breast
      cancer cell lines from the Integrative Cancer Biology Program (ICBP43). These
      signatures were investigated for their relationship to pro- and anti-apoptotic
      protein expression and drug response in breast cancer cell lines. RESULTS:
      Application of these signatures to breast tumor gene expression data identified
      two novel discrete phenotypes characterized by concordant, aberrant activation of
      either the HER2, IGF1R, and AKT pathways ("the survival phenotype") or the EGFR,
      KRAS (G12V), RAF1, and BAD pathways ("the growth phenotype"). These phenotypes
      described a significant amount of the variability in the total expression data
      across breast cancer tumors and characterized distinctive patterns in apoptosis
      evasion and drug response. The growth phenotype expressed lower levels of BIM and
      higher levels of MCL-1 proteins. Further, the growth phenotype was more sensitive
      to common chemotherapies and targeted therapies directed at EGFR and MEK.
      Alternatively, the survival phenotype was more sensitive to drugs inhibiting
      HER2, PI3K, AKT, and mTOR, but more resistant to chemotherapies. CONCLUSIONS:
      Gene expression profiling revealed a bifurcation pattern in GFRN activity
      represented by two discrete phenotypes. These phenotypes correlate to unique
      mechanisms of apoptosis and drug response and have the potential of pinpointing
      targetable aberration(s) for more effective breast cancer treatments.

PMID- 28446244
TI  - Ketogenic diet in the treatment of epilepsy in children under the age of 2 years:
      study protocol for a randomised controlled trial.
AB  - BACKGROUND: The incidence of epilepsy is greatest in the first 2 years of life,
      an age group where there is generally a poor prognosis for both seizure control
      and neurodevelopmental outcome. Early control of seizures can be associated with
      better developmental outcome but many of the epilepsies presenting in infancy are
      poorly responsive to antiepileptic medication. The ketogenic diet (KD) is a high
      fat, low-carbohydrate diet designed to mimic the effects of starvation on the
      body. Dietary fat is converted into ketones in the body and used as an energy
      source by the brain. The KD has been shown to be successful in controlling
      seizures in many observational studies, and in two randomised controlled trials
      (RCTs) in older children. However, little evidence is available in the very
      young. METHODS/DESIGN: An open-label RCT where eligible children (age 3 months to
      2 years with epilepsy who have failed two antiepileptic drugs (AEDs)) undergo
      baseline assessment, including medical and seizure history. Participants then
      start an observation period (7 or 14 days) with documentation of seizure
      frequency. Randomisation will occur on day 8 or day 15 to receive the KD or a
      further AED; the allocated treatment will commence on day 15, with instruction
      and training. A second assessment (4 weeks after start of treatment) will include
      a clinical review and tolerability questionnaire (modified Hague Scale of Side
      Effects - for those allocated to the KD group). Assessments will be repeated at 8
      weeks after the start of treatment including biochemical investigations, after
      which, according to patient response, KD (diet group) or AED (standard AED group)
      will then be continued or changed. Those in the AED group who have failed to
      achieve seizure control at the 8-week assessment will then be offered KD outside
      the context of the trial. Those in the KD arm who fail to achieve seizure control
      will be changed to standard clinical management. All patients will be followed up
      for 12 months from randomisation for retention, seizure outcome, quality of life
      and neurodevelopmental status. DISCUSSION: The slow rate of recruitment is an
      ongoing practical issue. There is a limitation to the number of eligible patients
      compared to what was predicted, mainly due to the nature of this patient group.
      After a substantial amendment to widen inclusion criteria and reduce the baseline
      period to 7 days for patients with a high seizure burden, the rate of recruitment
      steadily increased. A number of operational concerns regarding dietetic time were
      also highlighted impacting on the recruitment rate. However, the combination of a
      low dropout rate and the opening of further centres, the trial should
      successfully meet the final recruitment target. All nine centres are now
      recruiting and we hope to open further centres within the UK. TRIAL REGISTRATION:
      ClinicalTrials.gov, identifier: NCT02205931 . Registered on 16 December 2013.

PMID- 28446246
TI  - The role of rk39 serologic test in the diagnosis of visceral leishmaniasis in a
      Tertiary Hospital, Northern Ethiopia.
AB  - BACKGROUND: The study is done in Ayder Referral Hospital in Northern Ethiopia.
      Ethiopia is one of the countries where visceral leishmaniasis (VL) is endemic.
      Diagnosis of VL in Ethiopia is primarily based on rK39 immunochromatographic
      (rk39-ICT) strip. This test has been shown to have variable sensitivity and
      specificity in different countries. Hence the objective of the study is to
      determine the sensitivity and specificity of rk39-ICT in the diagnosis of VL in
      our set up. The study participants were VL suspected patients admitted to the
      hospital. A cross sectional study design was used. The study was conducted from
      January 14, 2013 to June 26, 2015. The rK39-ICT strip used was the InBios brand.
      Ethical clearance was obtained from the IRB of the college and written consent
      was obtained from the individual patients. RESULTS: A total of 62 VL suspects
      were involved in the study. The mean age was 26.3 years (SD = 6.94 years) with a
      median age of 25.5 years. Sixty-one (98.4%) of the patients was males. The rK39
      ICT was positive in 50 (80.6%) of the patients. Splenic aspiration was positive
      in 44 (71%) of the patients. In 37 (59.7%) of the patients both rK39 and splenic
      aspiration were positive. Thirteen (21%) of the patients had positive rK39 but
      negative splenic aspiration. Five (8.1%) of the patients had both negative rK39
      and splenic aspiration however seven (11.3%) of the patients had rk39 negative
      but splenic aspiration positive. The sensitivity, specificity, positive
      predictive value and the negative predictive value of rK39-ICT, taking splenic
      aspiration as a gold standard test, is 84.1% (95% CI 69.9-93.4%), 27.8% (95% CI
      9.7-53.5%), 74.0% (95% CI 60-85.4%) and 41.7% (95% CI 15.2-72.3%) respectively.
      CONCLUSION: Sensitivity of rK39-ICT is low and its specificity is poor in our set
      up. Significant number of patients with confirmed VL did not have travel history
      to endemic areas. We recommend that the rK39-ICT needs improvement for clinical
      use in our set up and case definition for visceral leishmaniasis in Ethiopia
      needs to be revisited.

PMID- 28446245
TI  - Mining a differential sialotranscriptome of Rhipicephalus microplus guides
      antigen discovery to formulate a vaccine that reduces tick infestations.
AB  - BACKGROUND: Ticks cause massive damage to livestock and vaccines are one
      sustainable substitute for the acaricides currently heavily used to control
      infestations. To guide antigen discovery for a vaccine that targets the gamut of
      parasitic strategies mediated by tick saliva and enables immunological memory, we
      exploited a transcriptome constructed from salivary glands from all stages of
      Rhipicephalus microplus ticks feeding on genetically tick-resistant and
      susceptible bovines. RESULTS: Different levels of host anti-tick immunity
      affected gene expression in tick salivary glands; we thus selected four proteins
      encoded by genes weakly expressed in ticks attempting to feed on resistant hosts
      or otherwise abundantly expressed in ticks fed on susceptible hosts; these
      sialoproteins mediate four functions of parasitism deployed by male ticks and
      that do not induce antibodies in naturally infected, susceptible bovines. We then
      evaluated in tick-susceptible heifers an alum-adjuvanted vaccine formulated with
      recombinant proteins. Parasite performance (i.e. weight and numbers of females
      finishing their parasitic cycle) and titres of antigen-specific antibodies were
      significantly reduced or increased, respectively, in vaccinated versus control
      heifers, conferring an efficacy of 73.2%; two of the antigens were strong
      immunogens, rich in predicted T-cell epitopes and challenge infestations boosted
      antibody responses against them. CONCLUSION: Mining sialotranscriptomes guided by
      the immunity of tick-resistant hosts selected important targets and infestations
      boosted immune memory against salivary antigens.

PMID- 28446243
TI  - Targeting metabotropic glutamate receptors for novel treatments of schizophrenia.
AB  - Support for the N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis of
      schizophrenia has led to increasing focus on restoring proper glutamatergic
      signaling as an approach for treatment of this devastating disease. The ability
      of metabotropic glutamate (mGlu) receptors to modulate glutamatergic
      neurotransmission has thus attracted considerable attention for the development
      of novel antipsychotics. Consisting of eight subtypes classified into three
      groups based on sequence homology, signal transduction, and pharmacology, the
      mGlu receptors provide a wide range of targets to modulate NMDAR function as well
      as glutamate release. Recently, allosteric modulators of mGlu receptors have been
      developed that allow unprecedented selectivity among subtypes, not just groups,
      facilitating the investigation of the effects of subtype-specific modulation. In
      preclinical animal models, positive allosteric modulators (PAMs) of the group I
      mGlu receptor mGlu5 have efficacy across all three symptom domains of
      schizophrenia (positive, negative, and cognitive). The discovery and development
      of mGlu5 PAMs that display unique signal bias suggests that efficacy can be
      retained while avoiding the neurotoxic effects of earlier compounds.
      Interestingly, mGlu1 negative allosteric modulators (NAMs) appear efficacious in
      positive symptom models of the disease but are still in early preclinical
      development. While selective group II mGlu receptor (mGlu2/3) agonists have
      reached clinical trials but were unsuccessful, specific mGlu2 or mGlu3 receptor
      targeting still hold great promise. Genetic studies implicated mGlu2 in the
      antipsychotic effects of group II agonists and mGlu2 PAMs have since entered into
      clinical trials. Additionally, mGlu3 appears to play an important role in
      cognition, may confer neuroprotective effects, and thus is a promising target to
      alleviate cognitive deficits in schizophrenia. Although group III mGlu receptors
      (mGlu4/6/7/8) have attracted less attention, mGlu4 agonists and PAMs appear to
      have efficacy across all three symptoms domains in preclinical models. The recent
      discovery of heterodimers comprising mGlu2 and mGlu4 may explain the efficacy of
      mGlu4 selective compounds but this remains to be determined. Taken together,
      compounds targeting mGlu receptors, specifically subtype-selective allosteric
      modulators, provide a compelling alternative approach to fill the unmet clinical
      needs for patients with schizophrenia.

PMID- 28446247
TI  - Difference in oxidative stress tolerance between rice cultivars estimated with
      chlorophyll fluorescence analysis.
AB  - BACKGROUND: Oxidative stress is considered to be involved in growth retardation
      of plants when they are exposed to a variety of biotic and abiotic stresses.
      Despite its potential importance in improving crop production, comparative
      studies on oxidative stress tolerance between rice (Oryza sativa L.) cultivars
      are limited. This work describes the difference in term of oxidative stress
      tolerance between 72 rice cultivars. METHODS: 72 rice cultivars grown under
      naturally lit greenhouse were used in this study. Excised leaf discs were
      subjected to a low concentration of methyl viologen (paraquat), a chemical
      reagent known to generate reactive oxygen species in chloroplast. Chlorophyll
      fluorescence analysis using a two-dimensional fluorescence meter, ion leakage
      analysis as well as the measurement of chlorophyll contents were used to evaluate
      the oxidative stress tolerance of leaf discs. Furthermore, fluorescence
      intensities were finely analyzed based on new fluorescence theories that we have
      optimized. RESULTS: Treatment of leaf discs with methyl viologen caused
      differential decrease of maximum quantum yield of photosystem II (Fv/Fm) between
      cultivars. Decrease of Fv/Fm was also closely correlated with increase of ion
      leakage and decrease of chlorophyll a/b ratio. Fv/Fm was factorized into
      photochemical and non-photochemical parameters to classify rice cultivars into
      sensitive and tolerant ones. Among the 72 compared rice cultivars, the
      traditional cultivar Co13 was identified as the most tolerant to oxidative
      stress. Koshihikari, a dominant modern Japonica cultivar in Japan as well as
      IR58, one of the modern Indica breeding lines exhibited a strong tolerance to
      oxidative stress. CONCLUSIONS: Close correlation between Fv/Fm and chlorophyll
      a/b ratio provides a simple method to estimate oxidative stress tolerance,
      without measurement of chlorophyll fluorescence with special equipment. The fact
      that modern cultivars, especially major cultivars possessed tolerance to
      oxidative stress suggests that oxidative stress tolerance is one of the
      agricultural traits prerequisite for improvement of modern rice cultivars. Data
      presented in this study would enable breeding of rice cultivars having strong
      tolerance to oxidative stress.

PMID- 28446248
TI  - The therapeutic potential of three-dimensional multipotent mesenchymal stromal
      cell spheroids.
AB  - The efficiency of clinical trials involving transplantation of multipotent
      mesenchymal stromal cells (MSCs) is often insufficient due to harsh conditions
      present within the target tissue including hypoxia, low nutrient supply as well
      as inflammatory reactions. This indicates the necessity for optimization of cell
      based therapy approaches which might include either modification of the cell
      manufacturing process or specific cell pretreatment procedures prior to
      transplantation. Recent reports confirm evidence that the aggregation of MSCs
      into three-dimensional (3D) multicellular spheroids results in enhancement of the
      overall therapeutic potential of cells, by improving the anti-inflammatory and
      angiogenic properties, stemness and survival of MSCs after transplantation. Such
      an MSCs spheroid generation approach may open new opportunities for the
      enlargement of MSCs applications in clinical research and therapy. However, the
      unification and optimization of 3D spheroid generation techniques, including the
      selection of appropriate clinical-grade culture conditions and methods for their
      large-scale production, are still of great importance. The current review
      addresses questions regarding therapeutic-associated properties of 3D
      multicellular MSCs spheroids in vitro and during preclinical animal studies, with
      special attention to the possibilities of translating these research achievements
      toward further clinical manufacturing and applications.

PMID- 28446249
TI  - Adipose-derived mesenchymal stem cells modulate CD14++CD16+ expression on
      monocytes from sepsis patients in vitro via prostaglandin E2.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to reduce sepsis
      induced inflammation and improve survival in mouse models of sepsis. CD16+
      monocytes are proinflammatory and abundant in inflammatory conditions such as
      sepsis. The primary objective in this exploratory study was to determine the
      effects of adipose-derived MSCs (ASCs) on three subsets of monocytes from sepsis
      patients in vitro and to delineate the underlying mechanism. METHODS: This is a
      prospective cohort study of patients admitted to the medical intensive care unit
      (ICU) at an academic medical center. The levels of CD14++CD16+, CD14+CD16++, and
      CD14++CD16- monocytes from 23 patients in the early phase of severe sepsis or
      septic shock as well as 25 healthy volunteers were determined via flow cytometry
      after coculture with or without ASCs. To determine the molecular mechanisms, the
      effects of exogenous prostaglandin E2 (PGE2) and the cyclooxygenase-2 (COX-2)
      inhibitor NS-398 on monocyte phenotypes and cytokine expression were also
      examined. RESULTS: Basal levels of CD14++CD16+ but not CD14+CD16++ monocytes were
      significantly elevated in severe sepsis and septic shock. A positive linear
      relationship existed between the levels of CD14++CD16+ monocytes and the Acute
      Physiology and Chronic Health Evaluation (APACHE) II score as well as Sequential
      Organ Failure Assessment (SOFA) score. Coculture of ASCs with monocytes from
      sepsis patients for 24 h significantly reduced CD14++CD16+ expression while
      increasing the CD14++CD16- phenotype. The coculture also significantly elevated
      PGE2, COX-2, and prostaglandin E2 receptor (EP)4 levels generated from monocytes.
      Functionally, ASCs reduced the tumor necrosis factor (TNF)-alpha and increased
      the interleukin (IL)-10 secretion in monocytes of septic patients. Furthermore,
      the effects of ASCs on the CD14++CD16+ phenotype and cytokine expression were
      mimicked by exogenous PGE2 and abolished by the COX-2 inhibitor NS-398.
      Additionally, ASCs also modified levels of monocyte phenotypes in a mouse model
      of sepsis. CONCLUSIONS: Levels of CD14++CD16+ monocytes positively correlate with
      disease severity scores in the early phase of severe sepsis and septic shock.
      ASCs switch monocytes of sepsis patients from CD14++CD16+ to CD14++CD16- in vitro
      and modulate the production of inflammatory cytokines. The immunomodulatory
      effect of ASCs on monocytes is PGE2-dependent. ASCs may exert their therapeutic
      effect on sepsis via altering monocyte phenotypes and functions.

PMID- 28446251
TI  - Erratum to: The effectiveness of the paclitaxel-coated Luminor(r) balloon
      catheter versus an uncoated balloon catheter in superficial femoral and popliteal
      arteries in preventing vessel restenosis or reocclusion: study protocol for a
      randomized controlled trial.

PMID- 28446250
TI  - Nanoparticles based on essential metals and their phytotoxicity.
AB  - Nanomaterials in agriculture are becoming popular due to the impressive
      advantages of these particles. However, their bioavailability and toxicity are
      key features for their massive employment. Herein, we comprehensively summarize
      the latest findings on the phytotoxicity of nanomaterial products based on
      essential metals used in plant protection. The metal nanoparticles (NPs)
      synthesized from essential metals belong to the most commonly manufactured types
      of nanomaterials since they have unique physical and chemical properties and are
      used in agricultural and biotechnological applications, which are discussed. The
      paper discusses the interactions of nanomaterials and vascular plants, which are
      the subject of intensive research because plants closely interact with soil,
      water, and atmosphere; they are also part of the food chain. Regarding the
      accumulation of NPs in the plant body, their quantification and localization is
      still very unclear and further research in this area is necessary.

PMID- 28446252
TI  - Ring finger protein 43 associates with gastric cancer progression and attenuates
      the stemness of gastric cancer stem-like cells via the Wnt-beta/catenin signaling
      pathway.
AB  - BACKGROUND: Ring finger protein 43 (RNF43) is a member of the transmembrane E3
      ubiquitin ligase family that was originally found in stem cells and plays
      important roles in tumor formation and progression. Our previous study indicated
      that RNF43 might be a tumor suppressor protein in gastric cancer. Given its
      antagonistic relationship with leucine-rich repeat-containing G-protein-coupled
      receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of
      the potential role of RNF43 in gastric stem cancer cells is necessary. METHODS:
      Immunohistochemistry staining, western blot analysis, and quantitative reverse
      transcription polymerase chain reaction were used to determine the mRNA and
      protein expression level of RNF43 and other Wnt pathway factors. Gastric cancer
      stem-like cells were obtained from gastric cancer tumor and cell lines by
      tumorsphere culture. The adeno-associated virus system was used to upregulate
      RNF43 expression in cancer cells. Functional experiments including tumorsphere
      formation, chemotherapy resistance, surface marker detection, and tumor xenograft
      assay were performed to measure stem-like properties in gastric cancer stem-like
      cells after RNF43 overexpression. RESULTS: RNF43 loss was significantly
      associated with TNM stage, distant metastasis, and Lauren classification, and
      predicted worse prognosis in gastric cancer patients. RNF43 expression was even
      lower in tumorspheres derived from tumor tissues or cell lines compared with
      adherent cancer cells and normal gastric cells. Overexpression of RNF43 in
      gastric cancer cells impaired their stem-like properties, including sphere
      formation ability, chemoresistance in vitro, and tumorigenicity in vivo.
      Moreover, Wnt pathway-related proteins were decreased in RNF43-overexpressing
      cells, while Wnt pathway activators could reverse the trend to some extent.
      CONCLUSIONS: Our findings indicated that RNF43 might not only participate in
      gastric cancer progression, but also attenuate the stemness of gastric cancer
      stem-like cells through the Wnt/beta-catenin pathway.

PMID- 28446253
TI  - Promoting medication adherence among patients with bipolar disorder: a
      multicenter randomized controlled trial of a multifaceted intervention.
AB  - BACKGROUND: The present research aimed to investigate the efficacy of a
      multifaceted intervention that included motivational interviewing (MI) and
      psychoeducation in improving medication adherence (MA) among patients with
      bipolar disorder (BD). METHOD: A multicenter, cluster randomized, observer-blind,
      controlled, parallel-group trial was conducted in ten academic centers in Iran.
      Patients with BD were randomly assigned to the experimental group (EXP; n = 136)
      or the usual care group (UC; n = 134). The EXP group received five sessions of MI
      and psychoeducation together with their family members. The primary outcome
      measure was changes in scores on the Medication Adherence Rating Scale from
      baseline to 6 months post-intervention. Other outcome measures included serum
      levels of mood stabilizers, clinical symptoms, quality of life, as well as
      measures of intention, beliefs about medicine, perceived behavioral control,
      automaticity, action and coping planning, and adverse reactions. RESULTS:
      Medication adherence improved over time in both groups, but patients in the EXP
      group improved more (baseline score: 6.03; score at the sixth month: 9.55) than
      patients in the UC group (baseline score: 6.17; score at the sixth month: 6.67).
      In addition, patients in the EXP group showed greater improvement than patients
      in the UC group in almost all secondary outcomes 6 months following the
      intervention. CONCLUSIONS: Multifaceted interventions that include motivational
      interviewing and psychoeducation can significantly improve MA and clinical and
      functional outcomes in patients with BD. TRIAL REGISTRATION NUMBER: The trial was
      registered with theClinicalTrials.gov database (NCT02241863)
      https://clinicaltrials.gov/ct2/show/NCT02241863.

PMID- 28446254
TI  - Functional neuroimaging of sex differences in autobiographical memory recall in
      depression.
AB  - BACKGROUND: Females are more likely than males to develop major depressive
      disorder (MDD). The current study used fMRI to compare the neural correlates of
      autobiographical memory (AM) recall between males and females diagnosed with MDD.
      AM overgenerality is a persistent cognitive deficit in MDD, the magnitude of
      which is correlated with depressive severity only in females. Delineating the
      neurobiological correlates of this deficit may elucidate the nature of sex
      differences in the diathesis for developing MDD. METHODS: Participants included
      unmedicated males and females diagnosed with MDD (n = 20/group), and an age and
      sex matched healthy control group. AM recall in response to positive, negative,
      and neutral cue words was compared with a semantic memory task. RESULTS: The
      behavioral properties of AMs did not differ between MDD males and females. In
      contrast, main effects of sex on cerebral hemodynamic activity were observed in
      left dorsolateral prefrontal cortex and parahippocampal gyrus during recall of
      positive specific memories, and middle prefrontal cortex (mPFC), and precuneus
      during recall of negative specific memories. Moreover, main effects of diagnosis
      on regional hemodynamic activity were observed in left ventrolateral prefrontal
      cortex and mPFC during positive specific memory recall, and dorsal anterior
      cingulate cortex during negative specific memory recall. Sex * diagnosis
      interactions were evident in the dorsomedial prefrontal cortex, caudate, and
      precuneus during positive memory recall, and in the posterior cingulate cortex,
      insula, precuneus and thalamus during negative specific memory recall.
      CONCLUSIONS: The differential hemodynamic changes conceivably may reflect sex
      specific cognitive strategies during recall of AMs irrespective of the
      phenomenological properties of those memories.

PMID- 28446255
TI  - Diffuse Large B-Cell Lymphoma Presenting as Bilateral Internal Auditory Canal
      Lesions.

PMID- 28446256
TI  - Innovation, informed consent, health research and the Supreme Court: Montgomery v
      Lanarkshire - a brave new world?
AB  - The Supreme Court decision in Montgomery v Lanarkshire ([2015] UKSC11) has been
      hailed as a landmark not least because the Court enshrines the doctrine of
      informed consent formally into English law for the first time in relation to
      medical treatment. This paper explores the decision in Montgomery. It examines
      what its implications may be in the future for the consent process in relation to
      health research and innovative treatment and whether it may prove a watershed
      moment leading to changing dialogues and expectations in relation to consent.
      First, the paper explores the concept of 'informed consent' in clinical research
      as seen through international, Council of Europe and EU instruments. Second, it
      considers how English law currently governs the provision of information to
      research participants in the context of clinical research. It questions whether
      such an approach will be sustainable in the future. Third, it discusses the
      decision of the UK Supreme Court in Montgomery v Lanarkshire and asks what might
      be the impact of this Supreme Court decision in the health research context. It
      asks whether Montgomery may result in new approaches to consent in health
      research and innovative treatment.

PMID- 28446257
TI  - Ruptured Spinal Dermoid Cyst.

PMID- 28446258
TI  - Touchscreen interventions and the well-being of people with dementia and
      caregivers: a systematic review.
AB  - BACKGROUND: Dementia can have significant detrimental impacts on the well-being
      of those with the disease and their carers. A range of computer-based
      interventions, including touchscreen-based interventions have been researched for
      use with this population in the hope that they might improve psychological well
      being. This article reviews touchscreen-based interventions designed to be used
      by people with dementia (PWD), with a specific focus in assessing their impact on
      well-being. METHOD: The data bases, PsycInfo, ASSIA, Medline, CINAHL, and
      Cochrane Reviews were searched for touchscreen-based interventions designed to be
      used by PWD with reported psychological well-being outcomes. Methodological
      quality was assessed using Pluye and Hong's (2014) Mixed Methods Appraisal Tool
      (MMAT) checklist. RESULTS: Sixteen papers were eligible. They covered 14
      methodologically diverse interventions. Interventions were reported to be
      beneficial in relation to mental health, social interaction, and sense of
      mastery. Touchscreen interventions also reportedly benefit informal carers in
      relation to their perceived burden and the quality of their relationships with
      the people they care for. Key aspects included the user interface, provision of
      support, learning style, tailored content, appropriate challenge, ergonomics, and
      users' dementia progression. CONCLUSIONS: Whilst much of the existing research is
      relatively small-scale, the findings tentatively suggest that touchscreen-based
      interventions can improve the psychological well-being of PWD, and possibilities
      for more rigorous future research are suggested.

PMID- 28446259
TI  - Estimating the real incidence of invasive listeriosis through an integrated
      surveillance model in use in Lombardy (Italy, 2006-2014).
AB  - The annual incidence of listeriosis in Italy is lower (0.19-0.27 per 100 000
      inhabitants per year) than in Europe (0.34-0.52 per 100 000 inhabitants per
      year). Since the observed incidence of listeriosis may be biased downward for
      underdiagnosis or under-reporting, this work aims to estimate the real incidence
      of listeriosis during a 9-year period in the Lombardy region, Italy. Data on
      listeriosis cases were collected from national mandatory notification system
      (MAINF) and Laboratory-based Surveillance System (LabSS). The two sources were
      cross-matched and capture-recapture method was applied to estimate the number of
      undetected cases and the real incidence of invasive listeriosis. Five hundred and
      eighty invasive listeriosis cases were detected by the two sources between 2006
      and 2014: 50.2% were identified only via MAINF, 16.7% were recorded only via
      LabSS, overlaps occurred in 192 cases (33.1%). The mean annual incidence detected
      only by MAINF was 0.56 per 100 000 inhabitants, which rose to 0.67 per 100 000
      considering also the cases detected by LabSS. The capture-recapture method
      allowed to estimate an incidence of 0.84 per 100 000. The high incidence of
      listeriosis may be due to improved sensitivity of the surveillance system, but
      also reflect a real increase, associated with an increased population at risk.

PMID- 28446261
TI  - Epidemiological characteristics of breakthrough varicella infection during
      varicella outbreaks in Shanghai, 2008-2014.
AB  - The outbreaks of varicella occurring in kindergartens and schools are
      increasingly notified in Shanghai despite the implementation of one-dose
      varicella vaccination. We analyzed surveillance data on the notified outbreaks of
      varicella in Minhang District of Shanghai during 2008-2014. A total of 13 511
      varicella cases and 154 outbreaks involving 1558 (11.5%) cases were reported.
      Annual attack rates of outbreak-associated varicella in outbreak classes were
      5.5%-12%. The mean age of the outbreak-associated cases was 8.6 +/- 3.1 years.
      Among 1558 outbreak cases, 660 (42.4%) received one-dose varicella vaccine
      previously. The proportions of breakthrough varicella infection during outbreaks
      ranged from 21.5% in 2008 to 86.1% in 2014. Annual breakthrough infection rates
      in outbreak classes ranged from 5.4% to 7.4%. Breakthrough cases as index cases
      results in 9.7% of outbreaks, and the average duration of outbreaks was
      significantly longer in vaccinated cases as index cases than in unvaccinated
      cases as index cases (11.3 +/- 5.8 days vs. 8.6 +/- 6.1 days, P < 0.05). The mean
      time of breakthrough infection since vaccination was 6.2 +/- 2.3 years (range 0.6
      13.4 years). One-dose varicella vaccination cannot prevent the varicella
      outbreaks in kindergartens and schools. A second dose of varicella vaccine should
      be recommended for children.

PMID- 28446260
TI  - Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review
      of the available evidence.
AB  - In 2014, the Food and Drug Administration approved a new human papillomavirus 9
      valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18,
      which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five
      additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim
      of the current study was to systematically retrieve, qualitatively and
      quantitatively pool, as well as critically appraise all available evidence on
      9vHPV from randomized controlled trials (RCTs). We conducted a systematic review
      of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a
      systematic search of registered, completed, and ongoing RCTs. We retrieved and
      screened 227 records for eligibility. A total of 10 publications reported on
      RCTs' results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV
      have been registered on RCT registries. There is evidence that 9vHPV generated a
      response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine
      efficacy against five additional HPV type-related diseases was directly assessed
      on females aged 16-26 years (risk reduction against high-grade cervical, vulvar
      or vaginal disease = 96.7%, 95% CI 80.9%-99.8%). Bridging efficacy was
      demonstrated for males and females aged 9-15 years and males aged 16-26 years
      (the lower bound of the 95% CIs of both the geometric mean titer ratio and
      difference in seroconversion rates meeting the criteria for non-inferiority for
      all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated.
      Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV
      administration in subjects that previously received qHPV and 9vHPV efficacy in
      regimens containing fewer than three doses. The inclusion of additional HPV types
      in 9vHPV offers great potential to expand protection against HPV infection.
      However, the impact of 9vHPV on reducing the global burden of HPV-related disease
      will greatly depend on vaccine uptake, coverage, availability, and affordability.

PMID- 28446262
TI  - Dietary supplementation of branched-chain amino acids increases muscle net amino
      acid fluxes through elevating their substrate availability and intramuscular
      catabolism in young pigs.
AB  - Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic
      effects on muscle protein synthesis. However, little is known about their roles
      in the regulation of net AA fluxes across skeletal muscle in vivo. This study was
      aimed to investigate the effect and related mechanisms of dietary supplementation
      of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In
      all fourteen 4-week-old barrows were fed reduced-protein diets with or without
      supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral
      arterial and venous catheters, and fed once hourly with intraarterial infusion of
      p-amino hippurate. Arterial and venous plasma and muscle samples were obtained
      for the measurement of AA, branched-chain alpha-keto acids (BCKA) and 3
      methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC
      quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net
      fluxes of total essential AA, non-essential AA and AA. As for individual AA,
      muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and
      glutamine), along with those of histidine, methionine and several functional non
      essential AA (glycine, proline and serine), were increased by BCAA
      supplementation. The elevated muscle net AA fluxes were associated with the
      increase in arterial and intramuscular concentrations of BCAA and venous
      metabolites including BCKA and free fatty acids, and were also related to the
      decrease in the intramuscular concentration of 3-MH. Correlation analysis
      indicated that muscle net AA fluxes are highly and positively correlated with
      arterial BCAA concentrations and muscle net BCKA production. In conclusion,
      supplementing BCAA to reduced-protein diet increases the arterial concentrations
      and intramuscular catabolism of BCAA, both of which would contribute to an
      increase of muscle net AA fluxes in young pigs.

PMID- 28446263
TI  - Spectrum and Predictors of Refractory Status Epilepticus in a Developing Country.
AB  - OBJECTIVE: Refractory status epilepticus (RSE) can influence the outcome of
      status epilepticus (SE). In the present study, we report the aetiology and
      predictors of outcomes of RSE in a developing country. METHODS: This is a
      prospective hospital-based study of SE patients (continuous seizures for five
      minutes or more). Those who had SE persisting after two antiepileptic drugs were
      defined as having RSE. We present the demographic information, duration, and type
      of SE, and we note its severity using the status epilepticus severity score
      (STESS), its aetiology, comorbidities and imaging findings. The outcome of RSE
      was defined as cessation of seizures and the condition upon discharge, as
      assessed by the modified Rankin Scale. RESULTS: A total of 35 (42.5%) of our 81
      patients had RSE. The median duration of SE before starting treatment was 2 hours
      (range=0.008-160 h). The most common causes of RSE were stroke in 5 (14.3%),
      central nervous system (CNS) infections in 12 (34.3%) and metabolic
      encephalopathies in 13 (37.1%) patients. Some 21 (60%) patients had
      comorbidities, and the STESS was favourable in 7 (20%) patients. A total of 14
      (20%) patients died, but death was directly related to SE in only one of these.
      Some 10 patients had super-refractory status epilepticus, which was due to CNS
      infection in 5 (50%) and metabolic encephalopathy in 3 (30%). On multivariate
      analysis, an unfavourable STESS (p=0.05) and duration of SE before treatment
      (p=0.01) predicted RSE. Metabolic aetiology (p=0.05), mechanical ventilation (p60
      years (p=0.003) were predictors of poor outcomes. CONCLUSIONS: RSE was common
      (42.5%) among patients with SE in a tertiary care center in India. It was
      associated with high mortality and poor outcomes. Age above 60 years and
      metabolic aetiology were found to be predictors of poor outcomes.

PMID- 28446264
TI  - Hacettepe cartilage slicer: a novel cartilage slicer and its performance test
      results.
AB  - OBJECTIVE: This study investigated the performance of a cartilage slicer device
      referred to as the 'Hacettepe cartilage slicer'. METHODS: Forty-one cartilage
      pieces were harvested from eight fresh frozen human ears and measured in
      thickness with a digital micrometer. These pieces were randomly sliced using four
      different thickness settings and two different types of blades. The thicknesses
      of the slices and remaining pieces were measured also. Scanning electron
      microscopy was utilised to determine the surface smoothness of the slices.
      RESULTS: Thickness results showed a proportional increase with the increasing
      thickness setting, with a +/-0.1 mm margin of error. The measurements showed that
      over 95 per cent of the slices' structural integrity was preserved. Although both
      blades provided satisfactory results, scanning electron microscopy revealed that
      the slices cut with a single bevel blade had superior surface smoothness.
      CONCLUSION: To our knowledge, the current study is the first to evaluate the
      performance of a cartilage slicer device. Based on the thickness results, the
      Hacettepe cartilage slicer fulfilled its design goals: to consistently produce
      slices at the intended thickness with a +/-0.1 mm tolerance, and to preserve over
      95.3 per cent of cartilage thickness thereby ensuring undamaged, strong cartilage
      slices.

PMID- 28446265
TI  - A Case of Leptomeningeal Dissemination of Pilocytic Astrocytoma in a Child.
AB  - We present the case of a 2-year-old boy with progressive left-sided weakness and
      a cranial magnetic resonance imaging (MRI) scan showing a lesion with a cystic
      component in the right thalamus and basal ganglia. The lesion was subtotally
      resected and diagnosed as a pilocytic astrocytoma by histopathology. Tumor
      seeding along the surgical tract was seen on MRI 16 days and 10 weeks after
      surgery. The patient received vincristine and carboplatin, and MRI performed 4
      months after chemotherapy revealed no additional or residual lesions. This case
      illustrated that a World Health Organization grade I astrocytoma could
      disseminate along the surgical tract.

PMID- 28446266
TI  - Vascular function long term after Kawasaki disease: another piece of the puzzle?
AB  - BACKGROUND: Kawasaki disease is an acute systemic vasculitis. Cardiac
      complications are frequent and include endothelial dysfunction in patients with
      coronary anomalies. Thus far, endothelial dysfunction in patients with no
      coronary lesions is poorly understood. Our aim was to access the vascular
      function in adolescents and young adults long term after Kawasaki disease, but
      without coronary aneurysms or any other cardiac risk factors. METHODS: We carried
      out a single-centre prospective study in a Portuguese population. We evaluated
      two groups of subjects: (1) Kawasaki disease patients over 11 years of age,
      diagnosed >5 years ago, with no coronary lesions or any other risk factors for
      cardiovascular disease; (2) control group of individuals without cardiovascular
      risk factors. Patients and controls were clinically assessed. Endo-PAT and
      carotid intima-media thickness assessment were performed to determine vascular
      function. RESULTS: In total, 43 Kawasaki disease patients were assessed and
      compared with 43 controls. Kawasaki disease patients presented a decreased
      reactive hyperaemia index compared with controls (1.59+/-0.45 versus 1.98+/-0.41;
      p<0.001). Augmentation index was similar in both groups (-4.5+/-7 versus -5+/-9%;
      p 0.6). The mean carotid intima-media thickness was not significantly increased
      in the Kawasaki disease group. There were no statistically significant changes
      with regard to laboratory data. CONCLUSIONS: Children with Kawasaki disease may
      have long-term sequelae, even when there is no discernible coronary artery
      involvement in the acute stage of the disease. Further research is needed to
      assess whether known strategies to improve endothelial function would bring
      potential benefits to Kawasaki disease patients.

PMID- 28446268
TI  - [Relation of GSTM1 Polymorphism with Leukemia].
AB  - OBJECTIVE: To investigate the relation of GSTM1 polymorphism in leukemia patients
      with therapeutic efficacy and the main biological characteristics. METHODS: The
      GSTM1 genotypes were detected by nested PCR; the remission rate after 1 course of
      treatment and main biological characteristics at occurrence of leukemia were
      compared between AL patients with different GSTM1 genotypes, and their relation
      was analyzed. RESULTS: The remission rate and partial remission rate after 1
      course of treatment in patients with GSTM1-undeleted genotype were no
      significantly different from those in patients with GSTM1 null genotype
      (chi2=0.290, P>0.05). The stratification analysis showed that GSTM1 null genotype
      was not related with age, sex, WBC count, Hb level, plt count at initial
      diagnosis and spleen enlargenent or no(P>0.05). The comparison of AML and ALL
      with GSTM1 null genotype by Log-rank showed that the survival rate was no
      statistically different between AML and ALL patients(chi2=2.043, P>0.05), while
      the LDH level in serum of patients with GSTM1-undeleted genotype at initial
      diagnosis was statistically different from that in patients with GSTM1 null
      genotype (P=0.001). CONCLUSION: The GSTM1 genotype does not relate with remission
      and partial remission rates after 1 course treatment of AL patients, but relates
      with LDH level. GSTM1 null genotype deletion may play a role in risk of leukemia.

PMID- 28446267
TI  - [PRPS1 Expression in Children with Acute Leukemia and Its Clinical Significance].
AB  - OBJECTIVE: To investigate the correlation between the expression level of PRPS1
      and the clinical characteristics in children with acute leukemia(AL). METHODS:
      Real-time quantitative RT-PCR and Western blot were used to detect the level of
      PRPS1 mRNA and protein expression in bone marrow samples from 176 patients
      diagnosed as AL (126 cases were newly diagnosed and 50 cases in complete
      remission), and its relevance with clinical indicators was statistically
      analyzed. The bone marrow samples from 21 children with non-malignant
      hematological disease were used as controls. RESULTS: (1)In B-ALL group, the
      level of PRPS1 mRNA in newly diagnosed patients were significantly higher than
      that in control and than that in complete remission patients (both P<0.0001). In
      T-ALL and AML group, differences was only observed between newly diagnosed
      patients and complete remission patients(both P<0.0001); (2)In B-ALL group, the
      expression level of PRPS1 increase with along risk enhancement (P<0.01), while no
      significant difference was observed in T-ALL (P>0.05). In AML patients,
      expression difference was shown between low risk group and high risk
      group(P<0.05); (3)High PRPS1 mRNA expression level were associated with high WBC
      counts and MRD positive in B-ALL patients (P=0.020, P=0.026, respectively);
      (4)Expression of NT5C2, an essential gene for relapse and drug resistance, was
      found to be positively correlated with PRPS1 expression in AL samples(P<0.05).
      CONCLUSION: High expression of PRPS1 is relevant factor of unfavourable prognosis
      in B-ALL children, which suggest PRPS1 may be a new indicator for prognosis of
      pediatric B-ALL and an index to guide individualized chemotherapy.

PMID- 28446269
TI  - [Expression of Death Associated Protein Kinase 1 in Chronic Lymphocytic
      Leukemia].
AB  - OBJECTIVE: To explore the expression of death-associated protein kinase 1(DAPK1)
      in chronic lymphocytic leukemia(CLL). METHODS: The DAPK1 expression was studied
      by means of MEC1 cells and B lymphocytes from blood samples of the patients with
      CLL. The quantitative detection of mRNA and Western blot were used to detecte the
      expression of DAPK1 and autophagy-related genes at both mRNA and protein levels.
      RESULTS: mRNA quantitative detection and Western blot displayed that the DAPK1
      expression in the patients with CLL was silenced. So, the expression of DAPK1 and
      autophagy related genes in MEC1 cells was not significantly different, no matter
      the cells were treated with or without INF-gamma. CONCLUSION: Scilencing of DAPK1
      expression in CLL results in abnormality of autophagy behavior, thus leading to
      the occurence of disease.

PMID- 28446270
TI  - [Characteristics and Clinical Significance of CRLF2 Mutations in Adult Acute
      Lymphoblastic Leukemia].
AB  - OBJECTIVE: Cytokine receptor-like factor 2(CRLF2) plays an important role in the
      development of normal B lymphocytes, which can mediate early B cell proliferation
      and survival. The aim of this study was to investigate the mutations of CRLF2 and
      its clinical significance in adult patients with acute lymphoblastic
      leukemia(ALL). METHODS: Exons of CRLF2 were amplified, then the DNA was purified
      and sequenced; the frequency, position, types and clinical significance of CRLF2
      mutations were analyzed. RESULTS: 6 types of genetic alterations in CRLF2 were
      found, among them the R186S prompted better prognosis, while L86I, F232F and
      W255C associated with poor prognosis. CONCLUSION: CRLF2 mutations may play an
      important role in the development and progressions of adult patients with ALL,
      and these genetic abnormalities may associate with clinical outcome.

PMID- 28446271
TI  - [Expression of Aurora Family Genes in Acute Leukemia and Its Clinical
      Significance].
AB  - OBJECTIVE: To explore the mRNA expression of Aurora-A,B,C(AUR-A,B,C) in acute
      leukemia(AL) and their correlations with the clinical indications. METHODS: The
      mRNA expression levels of AUR-A,B,C in 73 cases of newly diagnosed AL (untreated
      group), 20 cases of AL with remission (remission group) and 14 healthy volunteers
      as control (healthy group) were detected by QRT-PCR, and the difference of
      expression levels in difference groups, their correlations with clinical
      indicators and the correlation between the AUR-A,B,C mRNA expression levels
      themselves were analyzed. RESULTS: The mRNA expression levels of AUR-A,B,C in
      untreated group were all higher than those in healthy group and remission
      group(P<0.01), but there was not significant difference between healthy group and
      remission group(P>0.05); the mRNA expressions of AUR-A,B,C in acute lymphoblastic
      leukemia(ALL) group were all significantly higher than that in AML group(P<0.01).
      The mRNA expression of AUR-A,B,C in high risk group was higher than that in low
      risk group(P<0.05), but there was no difference in mRNA expression of AUR-A,B,C
      between high risk group and middle risk group as well as between middle risk
      group and low risk group(P>0.05). The mRNA expression of AUR-A, B, C in CD34,
      CD71 and CD56 negative group was not statistically different from that in
      CD34,CD71 and CD56 positive group(P>0.05). In 73 cases of newly diagnosed AL, the
      mRNA expression levels of AUR-A, B significantly were positively correlated with
      lactate dehydrogenase(LDH) level and risk stratification (r=0.279, P=0.017;
      r=0.314, P=0.007 and r=0.277, P=0.018; r=0.349, P=0.002), while the mRNA
      expression levels of AUR-A, B were not significantly correlated with age, WBC
      count, blast ratio in bone marrow at initial diagnosis and remission or no
      remission after 1 cours of chemotherapy; the mRNA expression level of AUR-C was
      significantly positively correlated with WBC count (r=0.263, P=0.025), and LDH
      level (r=0.348, P=0.003) at initial diagnosis and risk stratificantion(r=0.376,
      P=0.001), and negatively correlated with age (r=-0.241, P=0.040), and was not
      significantly correlated with blast ratio in bone marrow at initial diagnosis and
      remission or noremission after 1 course of chemotherapy. There were significant
      positive correlations in the mRNA expression between AUR-A and B (r=0.444,
      P=0.000), AUR-B and C (r=0.763, P=0.000) as well as AUR-A and C (r=0.616,
      P=0.000). CONCLUSION: Aur-A, B, C mRNA were highly expressed in patients with
      newly diagnosed AL, moreover the mRNA expression levels of Aur-A,B,C were
      positively correlated with each other, the high expression of Aur-A, B, C are
      associated with leukemia types, risk stratification, WBC count and LDH level at
      initial diagnosis, so they all maybe used as the prognostic markers and potential
      therapeutic targets.

PMID- 28446272
TI  - [Efficacy Comparison of Different Salvage Treatment Regimens for Patients with
      Refractory/Relapsed Acute Myeloid Leukemia].
AB  - OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely
      MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid
      leukemia(AML) patients with primary induction failure and relapse. METHODS: The
      clinical data of 156 AML patients with primary induction failure and relapse,
      except patients with acute promyelocytic leukemia(APL), treated with any of the
      above 3 regimens in our center from January 2008 to April 2016 were analyzed
      retrospectively. According to the treatment regimens, 156 patients were divided
      into MAC group (n=60), FLAG group (n=45) and CAG group (n=51). The complete
      remission(CR), partial remissison(PR), overall survival(OS), disease-free
      survival(DFS) and adverse events during the treatment were analyzed, so as to
      compare and evaluate the efficacy and safety of the 3 different regimens.
      RESULTS: After 1 course of re-induction chemotherapy, CR in MAC group was
      significantly higher than that in FLAG and CAG group (55.4% vs 34.1% vs
      34.0%)(P<0.05). The OS was not statistically significantly different among 3
      groups (P>0.05) with a median OS of 11 months, 5.46 months and 10.2 months,
      respectively. The myelosuppression was the main adverse event with no significant
      difference among the groups(P>0.05). More patients treated with MAC regimen
      underwent febrile neutropenia (93.3% vs 86.7% vs 64.7%)(P<0.001). However, the
      incidence of fatal infections was not signicantly different among 3 groups(5% vs
      8.9% vs 5.9%)(P>0.05). CONCLUSION: Compared with FLAG and CAG regimen, the MAC
      regimen can enable more AML patients with primary induction failure and
      refractory to achieve CR without increasing severe adverse events,therefore,this
      regimen may provide a opportunity for patients to recieve hematopoietic stem cell
      transplantation.

PMID- 28446274
TI  - [Efficacy of Idarubicin-Based Stratified Therapy for Acute Promyelocytic
      Leukemia].
AB  - OBJECTIVE: To investigate the remission rate of all-transretinoic acid (ATRA)
      combined with arsenics acid(ATO) on acute promyelocytic leukemia, and the
      efficacy and safety of sequential consolidation therapy with idarubicin, all
      trans retinoic acid and arsenic trioxide/compound Huangdai tablet. METHODS:
      Between January 2011 and January 2016 years 22 patients with newly diagnosed
      acute promyelocytic leukemia who received ATRA combined with ATO till complete
      remission in our hospital were retrospectively analyzed. Rates of CR, early
      mortality, complications and duration of induction were analyzed. The
      low/intermediate risk patients received 1-2 courses of idarubicin (IDA) single
      agent chemotherapy, ATRA and compound Huangdai tablet /ATO alternative treatment
      of 4 cycles after complete remission; the high-risk patients received idarubicin
      and cytarabine chemotherapy, ATRA and compound Huangdai tablet /ATO alternative
      treatment of a total of 4 cycles for double-induction group. RESULTS: Double
      induction achieved a 100% CR rates after 28.23+/-1.6 days induction. During
      induction, the infection rate was 50%, 36.4% of patients had differentiation
      syndrome and 27.3% suffered from bleeding in different locations. The 5-year
      overall survival was 100% and relapse-free survival was 95.4%. CONCLUSION: This
      protocol has a good antileukemic effect. The combination of ATRA and ATO achieves
      extremely high complete reminssion rate and reduces coagulopathy to cut down
      early mortality. Sequential therapy with IDA, ATRA, and ATO as a consolidation
      regimen results in satisfactory clinical outcomes with tolerable side effects.

PMID- 28446273
TI  - [Effects of Quercetin on Chronic Myeloid Leukemia Cell Line Resistant to Imatinib
      and Its Mechanism].
AB  - OBJECTIVE: To explore the growth inhibitory effect of quercetin on imatinib
      resistant chronic myeloid leukemia cell lines and to clarify its involved
      mechanisms. METHODS: The cell viability was detected by trypan blue Staining,
      percentage of apoptotic cells and cell cycle distribution were detected by flow
      cytometry, the protein expression was detected by Western blot. RESULTS: Both
      inhibitory effect of proliferation and apoptosis-inducing effect were similar
      between the imatinib-resistant and -sensitive cell lines treated with 25 umol/L
      quercetin for 24 hours and with arrest of cell cycle at G2/M phase. Quercetin
      could not change the expression of BCR-ABL. The expression of gamma-H2AX was
      markedly enhanced and the phosphorylation of JNK up-regulated by quercetin in
      both imatinib-resistant and imatinib-sensitive cell lines. CONCLUSION: The growth
      of imatinib-resistant cells can be inhibited by quercetin, and the apoptosis of
      cells can be induced by quercetin, which may be related to cell cycle arrest in
      G2/M. The DNA damage and up-regulation of p-JNK may be involved in these
      processes.

PMID- 28446275
TI  - [Acute Promyelocytic Leukemia Developed during Imatinib Therapy for
      Gastrointestinal Stromal Tumors].
AB  - OBJECTIVE: To investigate the clinicopathologic and molecular characteristics of
      acute promyelocytic leukemia(APL) developed during imatinib therapy for
      gastrointestinal stromal tumors(GIST). METHODS: A 49-year-old woman was
      hospitalized for abdominal pain. The abdominal CT revealed a gastric mass.
      Laparoscopic resection of the tumor was performed. The histopathologic analysis
      showed poorly differentiated malignant cell infiltration with epithelioid
      features. Immunohistochemistry staining of these cells was positive for CD117 and
      CD34. GIST was confirmed and imatinib treatment was given. RESULTS: After 1
      year,the patient developed progressive pancytopenia. Bone marrow aspirate showed
      marked hyperplasia of bone marrow cells with 92.5% promyelocyte, consistent with
      APL. Cytogenetic analysis demonstrated t(15;17)(q22;q21) as the sole abnormality.
      PML/RARalpha fusion gene was positive and Kit mutation was negative. After
      combined treatment with ATRA, arsenic trioxide and idarubicin, patient achieved
      cytogenetic and molecular remission. CONCLUSION: The metachronous coexistence of
      GIST with APL is uncommon. The potential nonrandom association and causal
      relationship between these malignancies remained to be investigated. Further
      studies would be necessary to clarify the relationship between imatinib and
      secondary malignancies in GIST patients.

PMID- 28446276
TI  - [Clinical Features and Prognostic Factors of Children with Acute Lymphoblastic
      Leukemia in High-Risk Group].
AB  - OBJECTIVE: To explore the clinical features and prognostic factors of pediatric
      acute lymphoblastic leukemia (ALL) in high-risk (HR) group. METHODS: A total of
      421 children with ALL in the Children's Hospital of Soochow University from
      August 2008 to March 2013 were diagnosed and treated according to the Chinese
      Children Leukemia Group (CCLG)-2008 Protocol. Among different risk-groups, 148
      cases were stratified into the low-risk group and 191 cases were included in the
      moderate-risk group. Eight-two patients of the high-risk group were analyzed
      retrospectively for their clinical features, 5-year event-free survival (EFS)
      rate and overall survival (OS) rate. RESULTS: The median follow-up times of 82
      patients were 64 months(3.0-76.3 months), 55 patient achieved complete
      remission(CR) after 1 cycle of induction chemotherapy(CR rate 67.1%), 25 patients
      relapsed(30.5%) mainly in very early and early relapse phases, significantly
      different from the low-risk group (P=0.013), 27 pateitns died(32.9%). The 5-year
      pEFS and pOS were 57.20% and 58.5%, respectively. Ph+ or BCR/ABL+ and MRD>10-2 on
      the 33rd day in the high-risk group were 2 main factors influencing EFS and OS
      according to single factor analysis. Ph+ or BCR/ABL+ was an independent
      prognostic factor, however, the MRD value on the 33rd day was not statistically
      significant differente by virtue of COX regression analysis. CONCLUSION: The
      clinical feature of children with ALL in high risk group display low induction CR
      rate, high recurrence rate and the lower 5-year pEFS. Ph+ or BCR/ABL+ is regarded
      as an independent factor of poor prognosis.

PMID- 28446277
TI  - [Effect of RNA Interference-silenced TAK1 on Kasumi-1 cell Proliferation
      Inhibition Induced by As2O3 and Its Mechanism].
AB  - OBJECTIVE: To explore the effect of transforming growth factor-beta activated
      kinase-1(TAK1) gene silenced by RNA interference on proliferation inhibition of
      Kasumi-1 cells induced by As2O3 and its mechanism. METHODS: The experiments were
      divided into 4 groups, including control group(Kasumi-1 cells treated with non
      specific siRNA), TAK1 specific siRNA treated group (Kasumi 1 treated with TAK
      specific siRNA), As2O3 treated group (Kasumi 1 cells treated with As2O3) and
      combined treated group (Kasumi 1 cells treated with TAK1 specific siRNA plus
      As2O3). The proliferation inhibition rate of Kasami 1 cells was detected by CCK-8
      method, the apoptotic rate of cells was detected by flow eytometry, the
      expressions of TAK1, phosphorylated c-Jun N-terminal kinase(p-JNK) and apoptosis
      related proteins were detected by Western blot. RESULTS: As2O3 could inhibit
      Kasumi-1 cell proliferation in a dose-dependent manner between 0.5 to 20 umol/L
      with IC50 of (3.79+/-0.36) umol/L at 24 h, and also inhibit Kasumi-1 cell
      proliferation in a dose-dependent manner between 0.5 to 10 umol/L with IC50 of
      (2.38+/-0.17) umol/L at 48 h, but then the inhibitory effect reached plateau.
      After treating Kasumi-1 cells with TAK1 siRNA and 3.5 umol/L As2O3 for 24 h, the
      proliferation inhibition rate was (10.86+/-1.64)% and (49.80+/-2.19)%, meanwhile
      the apoptosis rate was (8.47+/-0.75)% and (24.78+/-2.14)%, all significantly
      higher than those in control group (P<0.05, P<0.01). The proliferation inhibition
      rate and apoptosis rate of the combined treated group were significantly higher
      than that in control and single treated groups (P<0.05, P<0.01), TAK1 silencing
      and 3.5 umol/L of As2O3 could decrease the expression of TAK1, p-JNK, c-Fos, c
      Jun and BCL-2 in different degrees, and increase the expression levels of BAX and
      the activated (cleaved) caspase-3, 9 with statistically significant differences
      as compared with control group (P< 0.05). When Kasumi-1 cells were treated with
      TAK1 specific siRNA plus As2O3 for 24 h, protein expression levels were all
      significantly greater than that in the single-treated groups (P< 0.05).
      CONCLUSION: TAK1 silencing and As2O3 can separately and synergistically inhibit
      Kasumi-1 cell proliferation which probably relates with the inducing apoptosis
      via the JNK and mitochondrial pathway. Meanwhile, TAK1 silencing enhances the
      inhibitory effect of As2O3 on Kasumi-1 cell proliferation.

PMID- 28446278
TI  - [Clinical Analysis for 42 Imatinib-resistant Patients with Chronic Myelogenous
      Leukemia].
AB  - OBJECTIVE: To analyze the kinase mutation ratio, related factors, effectiveness
      and safety of the second generation drugs for imatinib-resistant patients with
      chronic myeloid leukemia(CML). METHODS: COX proportional hazard regression model
      was used for unvariate and multvariate analysis of various factors affecting the
      kinase mutation and for evaluating the effectiveness and safety of second
      generation tyrosine kinase inhibitor(TKI). RESULTS: 13 kinds of mutation were
      detected in 19 out of 42 cases for 22 times, including 4 times of F359V, 3 times
      of E255K, 2 time for F359C, F317L, T315I, Y253H, 1 time for D256R, C250R, D276G,
      F486S, M244V, Y256H and G250E, 3 cases with mixed mutations. The main adverse
      effects of patients receiving nilotinib were skin rash and fluid retention, while
      that for patients receiving dasatinib were eyelid edema and elevated bilirubin.
      CONCLUSION: The WBC count, spleen enlargement degree, chromosome karyotypes,
      disease staging, drug used before treatment and time of acheiving CCyR are the
      related factors of the kinase mutations, but the patients receiving the second
      generation TKI can survive well.

PMID- 28446279
TI  - [Effect of Stromal Cell Co-culture on Drug Resistance of Acute Myeloid Leukemia
      Cells and its Mechanism].
AB  - OBJECTIVE: To study the effect of co-culture of stromal cells and acute myeloid
      leukemia(AML) cells on drug resistance of AML cells and its mechanism. METHODS:
      Stromal cells were co-cultured with acute myeloid leukemia cell HL-60 and then
      were treated with DNR, HHT and Ara-C for observing the sensitivity of HL-60 cells
      to drugs after incubation with HS-5. At the same time, the the inhibitor LY294002
      of PI3K/AKT signaling pathway was used to treat the cells, so as to explore
      whether the changes of HL-60 sensitivity is associated with the activation of
      PI3K/AKT signal pathway after co-culture of cells. RESULTS: The statistical
      results of HL-60 cell inhibition rate showed that the HL-60 cell sensitivity to
      drugs was decreased after incubation with HS-5, the mRNA quantitation and
      immunblot detection showed that PI3K/AKT signaling pathway was activated after co
      culture of HL-60 cells with HS-5 cells, in addition the CCND1, FOXO1, PTEN and
      other important genes were also changed significantly. CONCLUSION: After co
      culture of HL-60 cells with HS-5, some important molecules of PI3K/AKT signal
      pathway are changed, such as CCND1,FOXO1, PTEN, finally leading to the change of
      HL-60 cell sensitivity to drugs.

PMID- 28446280
TI  - [Treatment Selection of Elderly Acute Myeloid Leukemia Patients Guided by HCT-CI
      Score].
AB  - OBJECTIVE: To explore the feasibility of guiding the individalized treatment
      strategy for elderly AML patients by using hematopoietic cell transplantation
      comorbidity index(HCT-CI) score. METHODS: The clinical and biological data of 165
      elderly (260 years) AML patients in department of hematology of the first
      affiliated hospital of Wenzhou medical universtity from January 2000 to December
      2014 were analyzed retrospectively. The AML patients were divided into 3 groups:
      score 0-1, 2-3 and >=4 according to HCT-CI, then the patients in each group again
      were divided into standard chemotherapy group, low dose chemotherapy group and
      support therapy group accoriding to therapeutic regimens, and the efficacy of
      above mentioned 3 kinds of treatment and their effects on survival of ealderly
      AML patients were compared, the prognostic risk factors for patients were
      analyzed further. RESULTS: A total of 165 patients (100%) were followed-up, and
      the mean follow-up time was 309 days, median survival time was 210 days. The
      survival analysis showed that the patients in HCT-CI score 0-1 group and 2-3
      group banefited from chemotherapy, while the survival analysis of the HCT-CI
      score >=4 group showed that there were no significant differance in survival rate
      between support therapy and chemotherapy groups. The complete remission rate and
      early mortality of patients received low dose or standard dose chemotherapy in
      HCT-CI score 0-1, 2-3 and >=4 groups were not significantly different. Univariate
      analysis and multivariante analysis of COX ratio risk model showed that the EOCG
      PS>=2, WBC>=100*107/L at initial diagnosis and HCT-CI score >=4 were the
      independent risk factor affecting the prognosis of elderly AML patients. The
      median survival time of patients received chemotherapy and support therapy was
      840 and 150 d(P<0.01) in HCT-CI score 0-1 group respectively, 210 and 60 days
      (P<0.01) in HCT-CI score 2-3 group respectively, 130 and 90 days (P>0.05) in HCT
      CI score >=4 group, respectively. CONCLUSION: The HCT-CI score can be used as
      simple and feasible evaluation criteria to judge the selection of individualized
      treatment strategy for elderly AML patients.

PMID- 28446281
TI  - [Effect of CDK Inhibitor LS-007 on Acute Lymphoblastic Leukemia and Its
      Mechanism].
AB  - OBJECTIVE: To study the effect of cyclin dependent kinase(CDK) inhibitor LS-007
      on acute lymphoblastic leukemia and its mechanism. METHODS: The acute lymphocytic
      leukemia cell line was cultured and treated by LS-007, flavopiridol and ABT-199,
      then the changes of apoptosis-related factor mRNA and protein levels were
      detected by using mRNA quantitative PCR and Werstern blot. RESULTS: quantitative
      PCR and Western blot detection showed that the levels of antiapoptotic protein
      decreased significantly in acute lymphoblastic leukemia cells after LS-007
      treatment, and the pro-apoptotic effect of LS-007 combined with ABT-199 was much
      better. CONCLUSION: LS-007 can affect the phosphorylation of RNA polymerase sites
      and promote cell apoptosis through changing the activities of CDK, thus having
      some positive significance for relieving acute lymphoblastic leukemia.

PMID- 28446282
TI  - [Effects of Different Dosages of rhG-CSF on Duration of Aleucocytosis and
      Leukocytes Level after Chemotherapy of Patients with Hematologic Malignancies].
AB  - OBJECTIVE: To compare the effects of different dosages of rhG-CSF on duration of
      aleucocytosis and white blood cell counts after chemotherapy of patients with
      hematologic malignancies. METHODS: Ninety patients in our hospital from December
      2011 to June 2016 were chosen as study objects, and all of them were divided into
      3 groups: group A (rhG-CSF 200 ug/m2), group B(rhG-CSF 300 ug/m2) and group C(rhG
      CSF 400 ug/m2); 30 patients from January 2004 to January 2007 were chosen as
      control(control group). The WBC(min) and its duration, WBC(max) and its timepoint
      were compared among different groups. The infection rate, incidence of side
      reactions and total amount of rhG-CSF used in different groups were compared.
      RESULTS: In control group, WBC(min) was(1.30+/-0.11)*109/L, its duration was
      (3.2+/-0.7)d, WBC(max) was(5.14+/-0.41)*109/L, and its time point was (26.1+/
      1.8)d; these in group A were (3.14+/-0.23)*109/L,(2.7+/-1.0)d, (10.08+/
      0.69)*109/L and (14.9+/-1.8)d respectively; these in group B were (3.11+/
      0.32)*109/L, (0.9+/-0.5)d, (10.17+/-0.75)*109/L and(10.7+/-1.5)d respectively;
      these in group C were (3.15+/-0.30)*109/L,(0.5+/-0.3)d, (11.95+/-0.86)*109/L and
      (10.6+/-1.5)d, respectively. Compared with control group, the WBC(min) and
      WBC(max) were both increased significantly, the duration of WBC(min) was
      shortened and the timepoint of WBC(max) was moved up(P<0.05). The infection rate
      of group C (3.33%(1/30)) was significantly lower than that of control
      group(33.33%(10/30))(P<0.05), total used amount of rhG-CSF and incidence of side
      reactions were not statistically different among group A,B,C(P>0.05). CONCLUSION:
      Compared with low dosage of rhG-CSF, medium/high dosage of rhG-CSF can help to
      shorten duration of a leukocytosis after chemotherapy of patients.

PMID- 28446283
TI  - [Effects of Atorvastatin on Proliferation and Apoptosis of Leukemia Cell Line HL
      60 and Its Mechanism of Signal Pathway].
AB  - OBJECTIVE: To investigate the effect of atorvastatin on proliferation and
      apoptosis of leukemia cell line HL-60 and its mechanism of signal pathway.
      METHODS: The leukemia HL-60 cells in logarithmic growth phase were seeded in 96
      well plates and were treated with 1, 5 and 10 mol/L atorvastatin, then were
      cultured in the incubator (at 37  degrees C, 5% CO2) for 12 h, 24 h, 48 h. MTT
      colorimetric method was used to detect the proliferation leukemia cells, the
      apoptosis of leukemia cells was detected by flow cytometry; the expresion levels
      of phosphatidylinositol 3-kinase(PI3K), serine threonine protein kinase(ATK) and
      mTOR at mRNA and protein levels were detected by RT-PCR and Western blot
      respectively. The experiments included blank control group, the negative control
      group and drug-treated group. RESULTS: Atorvastatin could inhibit the
      proliferation of HL-60 cells. The treatment of HL-60 cells with 10 mol/L
      atorvastatin for 48 hours showed the strongest inhibition rate (39.78+/-3.00)%
      which was statistically significant different from negative control group
      (t=4.015, P<0.05) and the strongest induction-apoptosis effect on HL-60 cells
      (43.30+/-3.92)%, that was statistically significantly different from negative
      control group (t=3.624, P<0.05). After treatment with atorvastatin for 48 hours,
      the expression levels of PI3K,ATK and mTOR were decreased, in which the effect of
      10 mol/L atorvastatin was the most obvious; The expression levels of PI3K,ATK and
      mTOR were decreased by (37.04+/-4.15)%, (53.81+/-3.25)% and (40.62+/-2.41)
      respectively, significantly different from the negative control
      (t=4.806,3.800,4.313, P<0.05). CONCLUSION: Atorvastatin may inhibit the
      proliferation of HL-60 cells and induce apoptosis by inhibiting the PI3K/ATK/mTOR
      signaling pathway.

PMID- 28446284
TI  - [Correlation between Bone Marrow Fibrous Proliferation and Prognosis of Acute
      Myeloid Leukemia].
AB  - OBJECTIVE: To investigate the correlation between the bone marrow fibrous
      proliferation and the prognosis of acute myeloid leukemia(AML). METHODS: The
      quantitative method was used to analyze the reticulin fiber density (RFD) of AML
      patients. the bone marrow sections from 39 primary AML patients and 35 normal
      controls were collected to compare the RFD between these 2 groups. The prognosis
      value of RFD for AML were estimated by using appropriate statistical analysis.
      RESULTS: RFD in primary AML was significantly higher than that in normal
      controls(2.41%+/-0.23% vs 1.14%+/-0.06%)(P<0.05). Relapse-free survival(RFS)
      analysis showed that the patients with RFD more than 1.68% indicated poor RFS,
      and the overall survival(OS) analysis showed that patients with RFD more than
      2.66% indicated poor overall survival (P<0.05). Besides, there were no
      relationship between RFD and the BM blast count (r=0.01) and WBC counts (r=0.04)
      at diagnosis(P>0.05). CONCLUSION: The RFD in bone marrow is a high risk factor in
      poor prognosis of AML patients.

PMID- 28446285
TI  - [Effect of Autophagy on Homoharringtonine-treated K562 Cells].
AB  - OBJECTIVE: To study the effect of homoharringtonine (HHT) alone or combined with
      3-methyladenine (3-MA) , an autophagy inhibitor, on the apoptosis and autophagy
      of K562 cells. METHODS: K562 cells were treated with HHT(10 ng/ml) or HHT(10
      ng/ml) combined with 3-MA (1.5 mmol/L) for 1 to 8 days. The apoptosis of treated
      cells was tested by means of flow cytometry(FCM), and the autophagy levels were
      tested with RT-PCR, Western blot and electron microscopy. RESULTS: In the early
      stage of HHT-treated group, the apoptosis rate increased and decreased later.
      Beclin1 mRNA expression level and the LC3II/I ratio were declined firstly and
      increased later in HHT group. While combining with autophagy inhibitor 3-MA, both
      the Beclin1 mRNA expression level and the LC3II/I ratio were declined continually
      during the treated period. The activated caspase-3 protein expression level was
      also raised sustainability during both HHT and 3-MA cultured period. CONCLUSIONS:
      HHT can induce apoptosis of K562 cells, but the sustaining effect of HHT can
      induc autophagy of K562 cells, the combination of HHT with 3-MA may enhance the
      cytotoxicitic effect of HHT on K562 cells.

PMID- 28446286
TI  - [Salvage Trerapy for Patients with Relapsed and Refractory Lymphoma by Allogeneic
      Hematopoietic Stem Cell Transplantation].
AB  - OBJECTIVE: To assess the safety and efficacy of allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) in treating patients with relapsed and
      refractory lymphoma. METHODS: Thirty-one consecutive patients with relapsed or
      refractory lymphoma received allo-HSCT. Used conditioning regimens included
      conditioning based on BEAM regimen(12 cases), conditioning based on modified
      Bu/Cy regimen(11 cases), conditioning based on Cy/TBI regemen(6 cases) and
      conditioning of Bu/Cy regimen(1 case). For provention of GVHD, the MMF was used
      on the basis of classcal protocol consisting of CsA combined with MTX. The
      infused HSC included the HLA-matched related HSC(11 cases), HLA nonidentical
      related HSC(13 cases) and HLA-matched unrelated HSC(6 cases). The bone marrow
      plus peripheral blood HSC were infused in 21 cases, while only peripheral blood
      HSC were infused in 9 cases. Among the 31 cases of relapse/refractory lymphoma,
      18 patients were male and 13 were female, 4 cases were Hodgkin's lymphoma and 27
      cases were non-Hodgkin's lymphoma. ALL of the 31 patients were qualified, as they
      were not in complete remission (CR) or in advanced stage at the time of
      transplantation. RESULTS: Twenty-seven evaluable patients showed the engraftment
      of both neutrophil and platelet at a median of 12 days(range 10-20) and 13
      days(range 9-34) respectively, 9 cases developed II-IV aGVHD, and cGVHD was
      observed in 3 patients, 5 patients can not achieve CR at 3 months after
      transplantation, and 6 patients relapsed after CR, the median follow-up of all
      the 31 patients after transplantation was 11.5 months (ranged, 0-141 months), and
      the 2-year OS was 46.1%+/-9.5% with median survival of 40 (9-141) months in the
      15 survivors. The age (P<0.05), disease status before transplantation (P=0.020)
      and remission after transplantation(P=0.000) were significantly related with
      survival. Cox's proportional hazards regression model analysis showed that the
      age (P=0.041) and disease statue (P=0.020) before allo-HSCT were independent
      predictive factors for survival. CONCLUSION: Allo-HSCT is an optimal treatment
      strategy for the patients with relapsed and refractory lymphoma who failed to
      most, if not all, available options.

PMID- 28446287
TI  - [Prognostic Significance of Follicular Lymphoma International Prognostic Index 2
      (FLIPI2) in Follicular Lymphoma Patients Treated with Rituximab Maintenance].
AB  - OBJECTIVE: To investigate the prognostic significance of Follicular Lymphoma
      International Prognostic Index 2 (FLIPI2) in FL patients treated with rituximab
      maintenance. METHODS: A tatol of 140 newly diagnosed FL patients who received
      Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)
      chemotherapy in our department were retrospectively analyzed from December 2002
      to December 2014. Among 140 patients with FL 122 patients achieved response, from
      them 56 patients received R maintenance (RM) every 2 months for median 8 times
      (RM group) while the rest 66 patients did not receive further anti-lymphoma
      treatment (non-RM group). RESULTS: There was no statistical difference in age,
      sex, pathologic grading, staging, FLIPI or FLIPI2 between RM and non-RM groups.
      The 2-year progression-free survival (PFS) of RM and non-RM groups were 89.7% and
      77.6% (P=0.043) while the 2-year overall survival were 100% and 98.6% (P=0.131).
      FLIPI2 is a significant prognostic model either in the total cohort, RM or non-RM
      groups (P<0.001 all). In subgroup analysis, RM was able to decrease disease
      progression in low and intermediate-risk group of FLIPI2, while the 2-year PFS of
      RM and non-RM groups in high-risk group were similar (55.6% vs 46.9%)(P=0.920).
      CONCLUSION: FLIPI2 presents robust prognostic significance either in RM or OBS
      patients, the patients in FLIPI2 low and intermediate-risk group may benefite
      from RM, but the role of RM in high-risk patients should be further to
      investigate.

PMID- 28446288
TI  - [Values of Different Evaluation Criteria of Interim 18F-FDG PET/CT Scan for
      Prediction of Prognosis in Patients with DLBCL].
AB  - OBJECTIVE: To explore the prognostic value of interim 18F-FDG PET/CT (i-PET/CT)
      scan for the patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
      METHODS: A total of 70 cases of initially diagnosed of DLBCL by 158 18F-FDG
      PET/CT scans in our hospital were retrospectively analyzed. The 5-point scale,
      the Lugano classification and maximum standardized uptake value induction
      (DeltaSUVmax) criteria were used respectively to assess i-PET/CT scans. Receiver
      operating characteristics (ROC) analysis was used to determine an optimal cutoff
      for DeltaSUVmax. Progression-free survival (PFS) and overall survival (OS) times
      were estimated as prognostic indicators using the Kaplan-Meier method and Cox
      regression. RESULTS: Optimal cutoff to predict progression or death was 62% for
      DeltaSUVmax. The positive predictive value (PPV) for 2-year PFS and OS of i
      PET/CT diagnosed by 5-point scale was low, and could be improved by using the
      Lugano classification with decreased sensitivity or DeltaSUVmax criteria. Kaplan
      Meier survival curve analysis showed that the Lugano classification and
      DeltaSUVmax were good predictors for PFS and OS, respectively, while the 5-point
      scale could only predict OS. Cox regression univariate analysis showed that the
      International Prognostic Index (IPI) score was better to predict PFS than 5-point
      scale, but worse than the three assessments in predicting OS. COX regression
      multivariate analysis showed that DeltaSUVmax<62% was an independent risk factor
      of prognosis, while the Lugano classification was only the OS independent
      prognostic predictor. CONCLUSION: Assessing i-PET/CT by 5-point scale is a
      limited value for predicting PFS and OS in DLBCL patients. The Lugano
      classification is recommended to discriminate the patients with poorer outcomes.
      The DeltaSUVmax criteria for i-PET/CT of DLBCL patients is an independent
      prognostic predictor for PFS and OS, better than the IPI score.

PMID- 28446289
TI  - [Value of Pretherapeutic 18F-FDG PET/CT in the Diagnosis, Staging and Prognosis
      Evaluation of Adult Burkitt's Lymphoma].
AB  - OBJECTIVE: To investigate the value of pretherapeutic 18F-FDG PET/CT in the focus
      detection, staging and prognosis evaluation of adult Burkitt's lymphoma(BL).
      METHODS: The clinical data and detection results of 18F-FDG PET/CT scan of 18
      patients with BL before the treatment from December 2008 to February 2015 were
      analyzed retrospectively. The lesions distribution were observed, the maximal
      standard uptake value(SUVmax) of 18F-FDG by lesions and the maximal diameter of
      lymph nodes were measured. One-way analysis of variance was used to analyze the
      SUVmax, and the Spearman correlation was used to analyze the relationship between
      SUVmax and the maximum diameter of lymph nodes. The prognostic factors were
      analyzed by using Kaplan-Meier survival analysis. RESULTS: 18F-FDG PET/CT showed
      100% positive detection rate for 18 adults with BL, lymph nodal lesions were
      found in all the patients, and the most common area was lymphonodi coeliaci
      (9/18, 50%), 8 cases showed extranodal soft tissue involvement, 6 cases showed
      gastrointestinal tract, bone marrow involvement was detected in 7 cases, out of
      which the mutiple-focal involvement was found in 4 cases. The median SUVmax of
      lymph nodes, extranodal soft tissue and bone marrow was 11.7 (range of 3.4 to
      28.5), 9.85 (range of 6.7 to 21.9) and 11.8(range of 5.6 to 23.8), respectively,
      there were no significant differences among these 3 types of lesions (F=1.013,
      P=0.369). And the median SUVmax of all lesions was 16.5 (range of 8.8 to 28.5).
      The clinical staging of 2 patients (2/8, 11.1%) was changed by 18F-FDG PET/CT
      imaging. The univariate analysis revealed that only the IPI (international
      prognostic index) could be the prognostic factor (chi2=6.602, P=0.010), but the
      prognosis was not different between the patients below and above the median
      SUVmax of all lesions and lymph node (all P>0.05). CONCLUSION: BL in adult is an
      intensely 18F-FDG-avid tumor, the 18F-FDG PET/CT is an effective imaging tool for
      the detection and staging of this disease. In our study, the prognostic value of
      pretherapeutic 18F-FDG PET/CT still is unclear, that is not recommended for the
      prognosis of the adult BL patients.

PMID- 28446290
TI  - [Gene Polymorphism of Inflammation-related Cytokines Correlates with the
      Susceptibility to DLBCL].
AB  - OBJECTIVE: To investigate the relationship of gene polymorphisms of inflammattion
      related cytokines with incidence of diffuse large B-cell lymphoma(DLBCL) in Gansu
      Han population. METHODS: The gene polymorphism of inflammation-related cytokines
      were detected by high-resolution melting(HRM) curve. RESULTS: The homozygous CC
      genotype carrying IL-1RA rs4251961 gene locus was related with the risk of DLBCL
      in comparison with homozygous TT, the OR was 0.83 of homozygous CC, 95% CI=0.697
      0.997,P<0.05), while the C allele of IL-1RA rs4251961 gene locus significantly
      correlated with the high incidence of diffuse large B-cell lymphoma compared with
      T allele(OR=8.83, 95% CI=1.909-40.813,P<0.01). CONCLUSION: The minor allele C of
      IL-1RA rs4251961 gene locus significantly relates with the susceptibility to
      DLBCL.

PMID- 28446291
TI  - [Clinical Significance of Detecting CD4+ T Cells in Peripheral Blood of Patients
      with Follicular lymphoma].
AB  - OBJECTIVE: To investigate the changes of CD4+ T lymphocytes in peripheral blood
      of patients with follicular lymphoma and its clinical significance. METHODS:
      Blood samples were collected for detection of whole blood cells, including
      absolute monocyte count (AMC), absolute lymphocyte count (ALC), hemoglobin (Hb),
      platelet count (Plt). Age, sex, pathological grade, number of involved lymph
      nodes, bone marrow involvement (BMI), Ann Arbor stage, B symptoms, serum lactate
      dehydrogenase (LDH) and serum beta-2 microglobulin (beta2-MG) were recorded, the
      prognostic stratification was performed by using FLIPI and FLIPI-2. The T
      lymphocyte subsets were analyzed by flow cytometry, including the absolute number
      of CD4+ T lymphocytes (ACD4C) and the absolute number of CD8+ T lymphocytes
      (ACD8C). RESULTS: Patients were with higher Ann Arbor stage, Hb<120 g/L, LDH
      greater than the upper limit of normal, the number of lymph nodes were involved>
      4, the bone marrow was involvement, beta2-MG levels were high FLIPI score and
      FLIPI-2 score, AMC level was higher (P<0.05). There were no significant
      differences in ACD4C levels among different groups. Patients with AMC>=0.89*109/L
      showed a shorter progression-free survival (PFS) and a shorter overall survival
      time (OS) (P=0.010,0.002) as compared with patients with AMC<0.89*109/L. The
      patients with ACD4C>0.16*109/L had longer progression-free survival and overall
      survival time, as compared with patients with ACD4C <=0.16*109/L (P=0.016,0.012).
      Low ACD4C and high AMC related with shorter PFS and OS (P=0.013, 0.020).
      Univariate Cox regression analysis showed that age (P=0.026), bone marrow
      involvement (P=0.017), elevated LDH (P=0.001), beta2-MG (P=0.014), FLIPI and
      FLIP2 score (P= 0.004 and 0.000) related with a shorter PFS. Multivariable Cox
      regression analysis showed that Hb (P=0.015), elevated LDH (P=0.003), beta2-MG
      (P=0.045), bone marrow involvement (P=0.016) and FLIPI-2 score(P=0.003) related
      with short OS. ACD4C <=0.16*109/L was a factor influencing prognosis of FL
      patients (PFS and OS) (P<0.05). CONCLUSIONS: Low ACD4C levels relatees with poor
      prognosis of patients with FL, and the ACD4C levels may be an important predictor
      for FL disease and prognosis.

PMID- 28446292
TI  - [Relation of MiR-34a Expression in Diffuse Large B Cell Lymphoma with Clinical
      Prognosis].
AB  - OBJECTIVE: To investigate the expression of miR-34a in serum of DLBCL patients,
      and to analyze its correlation with the expression of BCL-2 protein and clinical
      prognosis. METHODS: The clinical data of 65 DLBCL patients and 22 cases of
      lymphonode reactive hyperplasia (RH) were collected, the serum expressions of miR
      34a and BCL-2 were detected by real-time fluorescence quantitative PCR, and the
      relationship of miR-34a and BCL-2 expression with clinical pathological features
      and prognosis was analyzed. RESULTS: The miR-34a lowly expressed in DLBCL and the
      BCL-2 highly expressed in DLBCL, the miR-34a expression level correlated
      negatively with BCL-2 expression (P<0.01). The survival time of patients with
      high expression of miR-34a was significantly longer than that of patients with
      miR-34a low expression. Multivariate Cox regression analysis revealed that the
      expression of miR-34a (P<0.01) and BCL-2 (P<0.01) as well as clinical staging
      (P<0.01) were independent factors influencing the prognosis of patients with
      DLBCL. CONCLUSION: The low expression of miR-34a in DLBCL patients may be
      involved in the occurrence and development of diffuse large B cell lymphoma, the
      MiR-34a is correlated with prognosis of diffuse large B cell lymphoma.

PMID- 28446293
TI  - [Clinical Significance of Peripheral blood EB Virus Detection in NK/T Cell
      Lymphoma Patients].
AB  - OBJECTIVE: To explore the clinical significance of peripheral blood EB virus
      detection in NK/T cell lymphoma patients. METHODS: The positive rate of EB virus
      and EBV-DNA in 85 cases of NK/T cell lymphoma was assayed; the correlation of
      positive rate of EB virus with clinical staging, short-term and long-term
      prognosis was analyzed. RESULTS: The positive rate of EB virus in NK/T cell
      lymphoma was high (80.00%). The EBV-DNA copy number in peripheral blood
      leukocytes was higher than that in peripheral plasma (P<0.05), but there was no
      significant difference in EBV-DNA level between peripheral leukocytes and serum
      (P>0.05). The I-II stages ratio of patients in EBV+ group was significantly lower
      than that in EBV- group. The CR rate and ORR in EBV+ group was significantly
      lower than those in EBV- group, the 3 year OS rate and 3 year DFR in EBV+ group
      also was significantly lower than those in EBV- group. CONCLUSION: The detection
      of periphera blood EBV may be used as an reference indicator for anxiliary
      diagnosis of NK/T cell lymphoma and evaluation of prognosis for patients, thus
      possessing a certain value for clinical application.

PMID- 28446294
TI  - [Effect of Hedgehog Signaling Pathway Abnormality on Chemothe-rapeutic Resistance
      of Multiple Myeloma].
AB  - OBJECTIVE: To study the correlation between the excessive activation of Hedgehog
      signal and the drug resistance of multiple myeloma. METHODS: The resistant cell
      line RPMI 8226/R of multiple myeloma was established by an ascending
      concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R,
      RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit
      8) assay was used to detect the cell proliferation inhibition rate in 4 groups;
      the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and
      Sufu in the RPMI8226/S and RPMI8226/R cells. The Western blot was used to detect
      the expression of the resistant protein Cyclin D1, P21 and BCL-2 and MDR-related
      signaling pathways protein p-Akt, p-MAPK and STAT3 in the RPMI8226/S and
      RPMI8226/R cells. After adding different concentration of GANT61, the Western
      blot was used to detect the expression of Gli2 in RPMI8226/R and RPMI8226/S
      cells. RESULTS: The expression of Shh, Ihh, Smo Gli2 was enhanced significantly
      in the RPMI8226/R cells, but the expression of Sufu inhibitor was reduced, the
      expression level of related protein in Hedgehog signaling pathway was
      significanly higher in RPMI8226/R than that in RPMI8226/S. After theatment of
      GANT61 in vitro, the expression level of Gli2 in multiple myelom cells obviously
      decreased, the decreasing effect of GANT61 on Gli2 expression in RPMI8226/R cells
      was more significant than that in RPMI8226/S cells. The sensitivity of RPMI8226/R
      cells to DOX after treatment with GANT61 (IC50) was risen from 7.11+/-0.061
      umol/L to 0.99+/-0.053 umol/L, the corresponding cell resistance index decreased
      from 5.51 to 1.69. CONCLUSION: the activation of Hedgehog signaling pathway is
      closely related with the resistance of multiple myeloma cells, and GANT61 can
      block the Hedgehog signaling pathway, thus Hedgehog signaling may be used as a
      new target for multiple myeloma treatment.

PMID- 28446295
TI  - [Circulating Serum MicroRNA as Diagnostic Biomarkers for Multiple Myeloma].
AB  - OBJECTIVE: To investigate the diagnostic value of circulating serum miRNA for
      multiple myeloma. METHODS: Forty blood samples from patients with multiple
      myeloma were collected from July 2013 to June 2014 in Department of Hematology,
      Zhongshan Hospital Affiliated to Xiamen University. The real-time quantitative
      PCR was performed to detect the serum expression levels of miRNAs (miR-29a, miR
      155, miR-16 and miR-92a) circulating in the different stages of patients with
      multiple myeloma and evaluate the diagnostic value for patients with multiple
      myeloma. RESULTS: The serum level of miR-29a significantly increased in newly
      diagnosed patients as compared to healthy donor (P<0.01), serum miR-155 levels
      were significantly lower as compared with healthy donor(P<0.001); The ratio of
      miR-29a and miR-155 was an effective biomarker for distinguishing multiple
      myeloma from healthy donor, their sensitivity and specificity were 80.8% and
      83.3% respectively for myeloma diagnosis. the change of miR-29a expression was
      consistent with the changes of bone marrow plasma cells and M protein levels.
      CONCLUSION: These circulating serum microRNA, such as miR-29a, miR-155 and miR
      16, may serve as potential diagnostic biomarkers for multiple myeloma, and the
      ratio of miR-29a/miR-155 may serve as a most useful biomarker for myeloma
      diagnosis.

PMID- 28446296
TI  - [Expression of CC-chemokine Receptor 7 in Patiens with Multiple Myeloma and Its
      Relationship with Extramedullary Disease].
AB  - OBJECTIVE: To investigate the expression of CC-chemokine receptor 7(CCR7) in
      patients with multiple myeloma(MM) and its correlation with clinical features of
      MM. METHODS: The level of CCR7 expression in bone marrow samples from 53 newly
      diagnosed MM patients was detected by flow cytometry(FCM). Statistical methods
      were used to analyze the correlation between CCR7 expression and clinical
      features, such as sex, age, M protein, peripheral blood cell count, biochemical
      indicators, plasma cell ratio of bone marrow, immunophenotype, osteopathy and
      extramedullary disease. RESULTS: The plasma cells in 24 out of 53 cases(45.28%)
      expressed CCR7. The rate of extramedullary disease in CCR7 positive group was
      significantly higher than that in CCR7 negative group (29.17% vs 3.45%)(P<0.05).
      CONCLUSION: The expression of CCR7 in patients with MM is high, moreover this
      high expression correlates with extramedullary disease, thus CCR7 can be used as
      an effective indicator for prediction of extramedullary disease.

PMID- 28446298
TI  - [Clinical Effects of Different Chemotherapeutic Regimens on the Patients with
      Multiple Myeloma].
AB  - OBJECTIVE: To explore the clinical effects of T-VD regimen
      (bortezomib+dexamethasone+thalidomid) and T-VAD regimen
      (vincristine+adriamycin+dexamethasone+thalidomide) on the patients with multiple
      myeloma(MM). METHODS: Thirty cases of MM treated by T-VD(T-VD group) and 30 cases
      of MM treated by T-VAD(T-VAD group) from April 2010 to April 2012 were included
      in this study. The clinical effects and long-term survival were compared betwwen
      these 2 groups. RESULTS: Both the CR and ORR in T-VD group were higher than those
      in T-VAD group(P<0.05); the ORR of the non-light and light chain type in T-VD
      group was higher than that in the T-VAD group(P<0.05); the ORR was not different
      between the no-light chain type and light chain type in T-VD group(P>0.05); the
      ORR was not different between the non-light and light chain type of T-VAD
      group(P>0.05); the ORR was not different between the stage I-II of T-VD group and
      T-VAD group(P>0.05); the ORR for the stages of III T-VD group was higher than
      that of T-VAD group(P<0.05); the ORR was not different between the I-II and III
      stages in the T-VD group(P>0.05); The ORR for the I-II stages of control group
      were higher than that of the III stages(P<0.05); the levels of serum M protein,
      myeloma cells, beta2-MG in the T-VD group were lower than those in T-VAD
      group(P<0.05). The rate of leukocyteopenia, nausea and vomit, weakness in T-VD
      group were significantly higher than those in T-VAD group(P<0.05); The incidences
      of infection and peripheral neuropathy in T-VD group were higher than those in T
      VAD group(P<0.05). CONCLUSION: The effect of T-VD regimen on the patients with MM
      is better than that of T-VAD regimen and its effect is not influenced by the
      clinical classification and stages, but will aggravate some side effects, thus
      this chemotherapeutic regimen need to be carefully chosen.

PMID- 28446297
TI  - [Prophylaxis of Bortezomib-Induced Peripheral Neuropathy in Patients with
      Multiple Myeloma by High-Dose Intravenous Mecobalamin].
AB  - OBJECTIVE: To evaluate the efficacy and safety of high-dose intravenous
      mecobalamin (HDIME) for the treatment of bortezomib-induced peripheral
      neuropathy(BIPN) in the patients with multiple myeloma (MM). METHODS: A total of
      65 newly diagonsed patients with multiple myeloma receiving bortezomib in Tianjin
      Medical University General Hospital were enrolled in this single-centre
      randomized clinical trial from July 2012 to May 2016. Out of 65 patients 38 in
      control group received bortezomib-based chemotherapy and 27 patients in HDIME
      group received the additional high-dose intravenous mecobalamin. RESULTS: The
      incidence of BIPN in HDIME group was lower than that in control group(29.63% vs
      55.26%, chi2=4.197,P<0.05). Whether the BIPN rate of Grade 2 or 3 and above in
      HDIME group significantly decreased as compared with control group(18.52% vs
      47.37%,chi2=5.746,P<0.05) (3.71% vs 21.05%, chi2=3.983,P<0.05). The BIPN rate of
      less than 5 cycles of bortezomib was not significantly different between HDIME
      and control groups(chi2=2.714,P>0.05). Overall effective rate of HDIME group and
      control group was 77.78% and 73.68%(P>0.05) respectively. Neither PFS nor OS was
      significantly different between HDIME group and control group(P>0.05). Treatment
      related toxicity was only mild rash in 1 case. No other side-effects including
      nausea, abdominal pain, and hypotension occurred. CONCLUSION: HDIME has a good
      efficacy for the prophylaxis BIPN and and without serious side effects.

PMID- 28446299
TI  - [Effect of CIK Cells Comined with VAD on Short Prognosis of Patients with
      Multiple Myeloma].
AB  - OBJECTIVE: To explore the effect of CIK cells comined with VAD regimen on
      prognosis of patients with multiple myeloma(MM). METHODS: Forty-six cases of MM
      were divided into observation group and control group, the control group was
      treated by VAD and the observation group was treated by CIK cells comined with
      VAD. The prognosis between 2 groups was compared. RESULTS: The total efficiency
      was not significantly different between the 2 groups (P>0.05); the CR in the
      observation group was significantly higher than that in control group(P<0.05);
      the levels of osteocytes in observation group were higher than those in control
      group(P<0.05); the levels of osteoclasts, plasma cells, IgA and IgG in
      observation group were lower than those in control group(P<0.05); the increasing
      ranges of albumin and hemoglobin, and the decreasing range of blood sedimentation
      and beta2-MG in observation group were higher than those in control
      group(P<0.05); the incidences of abnormal electrocardiogram, myocardial enzyme
      and creatinine in observation group were higher than those in control
      group(P<0.05). CONCLUSION: CIK cells comined with VAD regimen can enhance the
      therapeutic effects on the patients with multiple myeloma, improve the objective
      index and reduce the risk of adverse reactions, thus may be applicable to
      clinical practice.

PMID- 28446300
TI  - [Clinical Value of Serum Fructosamine Measurement in IgA Type Multiple Myeloma].
AB  - OBJECTIVE: To investigate the value of serum fructosamine (FMN) measurement in
      clinical typing and staging of multiple myeloma(MM) as well as evaluation of
      curative efficacy and prognosis of IgA type MM. METHODS: The levels of FMN were
      detected by nitro-blue-tetrazolium colorimetric method in 62 IgA type MM
      patients, 65 IgG type MM patients, 24 IgM type MM patients. The difference
      between the serum FMN levels and different MM types and its relationship with IgA
      type MM, patients' stages, efficacy and as well as, the effect of FMN level on
      overall survival (OS) time of IgA type MM patients were analyzed. RESULTS: FMN
      level of IgA type patients was obviously higher than that of IgG type and IgM
      type patients. Patients of DS stage III had higher FMN level than that of stage
      II, and patients of DS stage II had higher FMN level than that of stage I, the
      differences were statistical significant(P<0.05). Patients of ISS stage III also
      had higher FMN level than that of stage II, and patients of ISS stage II also had
      higher FMN level than that of stage I, the differences were statistical
      significant(P<0.05). After treatment, FMN level of patients obtained complete
      remission (CR) or very good partial remission(VGPR) obviously decreased, FMN
      level of patients obtained partial remission(PR) decreased, FMN level of patients
      obtained less than PR increased. Patients with normal FMN level had longer OS
      time, while patients with high FMN level had obviously short OS time.
      CONCLUSIONS: Serum FMN is obviously elevated in the IgA type MM, there is a
      certain association between staging and serum FMN level, the IgA type MM patients
      with FMN normalization after treatment have better prognosis.

PMID- 28446301
TI  - [Analysis of Gene Mutation Types of Thalassemia in Longyan Area of Fujian
      Province in China].
AB  - OBJECTIVE: To explore the type and distribution of thalassemia gene mutation in
      Longyan area of Fujian province in China, so as to provide a evidence for
      prenatal diagnosis and to reduce birth defects. METHODS: The mean corpuscular
      volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin electrophoresis
      were used for screened the mutation types of thalassemia. Genotyping of the
      screened positive sample was performed by gap single polymerase chain reaction
      (gap-PCR) and reverse dot blot hybridization (RDB). RESULTS: Out of 7823 cases of
      routine positive blood test, 2826 cases were positive (36.12%) by using
      hemoglobin electrophoresis; 1905 out of 2710 cases were diagnosed as
      Mediterranean anemia by genetic test, with 24.35% of carrying rate; 1225 cases
      were positive alpha thalassaemia and the carrying rate was 15.66%, their major
      genetic types were --SEA/alphaalpha,-alpha3.7/alphaalpha,-alpha3.7/--SEA and 
      alpha4.2/alphaalpha, with carrying rate of 12.91%, 1.28%, 0.51% and 0.74%,
      respectively; 632 cases were positive beta thalassaemia, with carrying rate of
      8.08%, the major genotypes were 654M/N,41-42M/N,17M/N,-28M/N and 27-28M/N and
      with carrying rate of 3.66%, 2.22%, 0.78%, 0.66% and 0.45%, respectively; 48
      cases were diagnosed as both alpha- and beta-thalassemia, with the carrying rate
      of 0.61%. CONCLUSION: The main gene mutation types of alpha- and beta-thalassemia
      in Longyan area of Fujian Province in China were --SEA/aa and 654 M/N. As
      thalassemia gene mutation prevalents in Fujian, the screening of thalassemia
      genotypes for childbearing age woman has great significance for raising
      population quality.

PMID- 28446302
TI  - [Telomere Length, Expression of MRE11 and Ku80 in Patients with Aplastic Anemia
      and Their Correlation with Pathogenesis].
AB  - OBJECTIVE: To detect the expression levels of MRE11 and Ku80 mRNA, and telomere
      length in bone marrow mononuclear cells of aplastic anemia(AA) patients, and to
      explore their correlation with pathogenesis of aplastic anemia. METHODS: Bone
      marrow mononuclear cells were collected from 40 cases of AA and 20 normal
      controls for detecting mRNA expression of MRE11 and Ku80 and telomere length by
      using real-time quantitative polymerase chain reaction (qPCR), then MRE11, Ku80
      and telomere length were analyzed for their correlation. RESULTS: As compared
      with controls, the expression levels of MRE11 and Ku80 in patients with AA were
      significantly reduced, and the telomere length in patients with AA was obviously
      shortened, respectively (P<0. 05). The telomere length was significantly shorter
      in the persons aged >=45 years in comparison with the AA patients and normal
      control younger than 45 years old (P<0.05). For the AA patients older than or
      equal to 45 years and less than 45 years in comparison with the controls at the
      same age, the telomere length was significantly shorter(P<0.05). The expression
      levels of MRE11 and Ku80 didn't correlate with telomere length (P>0.05). The mRNA
      expression level of MRE11 correlated positively and significantly with that of
      Ku80 (r=0.863, P<0.05). CONCLUSION: The change of telomere length may play an
      important role in the pathogenesis and progression of aplastic anemia. The lower
      expression of MRE11 and Ku80 may be involved in the pathogenesis of aplastic
      anemia.

PMID- 28446303
TI  - [Prognosis and Survival Analysis of Patients with Essential Thrombocythemia].
AB  - OBJECTIVE: To investigate the survival status and prognosis of patients with
      essential thrombocythemia(ET) and analyze the prognostic factors for the
      patients' survival, so as to provide a evidence for clinical treatment and
      prognosis evaluation. METHODS: A retrospective analysis of 118 patients with ET
      was conducted in the Fifth Affiliated Hospital of Sun Yat-Sen University and
      Zhongshan Municipale People's Hospital from December 2002 to December 2013. The
      clinical characteristics were summarized, such as the survival curve and multi
      factor analysis, therefore looking for the disease characteristics and risk
      factors affecting the survival and prognosis. RESULTS: Among 118 ET patients
      enrolled in this study, the survival rate of ET patients for 1, 3, 5 and 10 years
      were 95.5%,92.6%,89% and 81.6%, respectively. Kaplan-Meier survival curve showed
      that the age >=60 years old at diagnosis, cardiovascular risk factors, anamnesis
      of thrombosis or hemorrhage, anemia(hemoglobin<120 g/L), thrombocythemia (>=1
      000*109/L), risk stratification and hydroxyurea or HHT(hemoharringtonine) use in
      high-risk group were factors affecting the suvival rate, 7 out of those factors
      influencing survival rate were statistically significant (P<0.05). COX regression
      analysis showed that independent risk factors affecting survival have not yet
      been found. CONCLUSION: ET patients display a high survival rate and long
      survival time, and their conversion risk into the marrow fibrosis or leukemia has
      been found to be low. The age>=60 years old at diagnosis, cardiovascular risk
      factors, anamnesis of thrombosis or hemorrhage, anemia and therombocythemia are
      the risk factors affecting prognosis. The use of hydroxyurea or HHT in high-risk
      group can improve the prognosis.

PMID- 28446304
TI  - [IL-33 and sST2 levels in Serum of Children with Henoch-Sch?nlein Purpura and
      Their Clinical Significance].
AB  - OBJECTIVE: To investigate the serum IL-33 and sST2 levels in children with Henoch
      Schonlein purpura (HSP), and explore their clinical significance. METHODS: Total
      27 HSP patients and 22 healthy controls were enrolled in present study. The
      expressions of IL-33 and sST2 were measured by enzyme linked immunosorbent assay
      (ELISA). Using real-time quantitative polymerase chain reaction (RT-PCR), the
      mRNA expression of IL-33 and sST2 were detected in all subjects. RESULTS: The
      level of the IL-33 in the serum of HSP group and control group was 365.5+/-160.6
      pg/ml and 175.9+/-92.8 pg/ml(P< 0.05). The level of the sST2 was increased in the
      serum of HSP group (1788.6+/-523.8 pg/ml) as compared with that in control group
      (1083.6+/-489.6 pg/ml)(P>0.05), but the ratio of sST2/IL-33 in HSP patients was
      much lower than that in the controls(P<0.05), IL-33 and sST2 mRNA levels were up
      regulated in HSP patients by 5.47+/-1.97-fold(P<0.05) and 3.13+/-2.01
      fold(P<0.05) compared with controls, but sST2/IL-33 significantly decreased in
      HSP patients(P<0.05). CONCLUSION: The levels of IL-33 and sST2 increase in the
      serum of HSP patients, but the ratio of sST2/IL-33 is much lower than that in
      control.

PMID- 28446305
TI  - [Establishment of Mouse Model of H-2 Haploidentical Hematopoietic Stem Cell
      Transplantation from Double Donors].
AB  - OBJECTIVE: To establish a new mouse model of H-2 haploidentical stem cell
      transplantation from double donors (DHSCT) and compare with conventional
      haploidentical hematopoietic stem cell transplantation (HSCT) so as to alleviate
      transplant-related complications. METHODS: The recipients CB6F1 of conventional
      HSCT group were pretreated by 8 Gy total body irradiation(TBI), and received
      3*107 donor (male C57) spleen mononuclear cells (spMNC) mobilized by G-CSF within
      2 hours after TBI. Recipients CB6F1 of D-HSCT groups accepted 2 Gy TBI, and
      received total 12*107 spMNC mobilized by G-CSF from 2 donors within 2 hours after
      TBI, each donor donated 6*107 cells. According to the different strains and sex
      of donors, DHSCT were divided into 3 groups: in group A, the stem cells were from
      male C57 and female BALB/c; in group B, stem cells were from male C57 and male
      BALB/c, while the stem cells in group C were from male C57 and male C3H.
      Hematopoietic reconstruction, engraftment, GVHD and survival were observed among
      these 4 groups. RESULTS: The nadir of white blood cell count after conventional
      HSCT were lower than 1*109/L and lasted for 3 to 5 days, while not less than
      3*109/L after D-HSCT among either group A, B or C. The complete chimerism (CC) in
      conventional HSCT group was achieved quickly within only 1 week in peripheral
      blood. Mixed chimerism (MC) in peripheral blood was found within the first week
      after DHSCT among either group A, B or C, and transformed into stable CC within
      the second week eventually. Both GVHD morbidity and mortality of conventional
      HSCT were 100% at 34th day after transplantation.Among DHSCT groups,the overall
      GVHD morbidity and mortality at 34th day after transplant were 49.6% and
      50%(P<0.01,P<0.05), respectively,and 60.4% and 81.2% at 50th day after
      transplant. Overall survival of 50 days was 50.9% that indicated a long survival
      in such mice DHSCT. The differences of hematopoietic reconstruction, donor cell
      engraftment, GVHD incidence, GVHD mortality and OS were not statistically
      significant among group A, B and C(P>0.05). CONCLUSION: A new mouse model of H-2
      haploidentical peripheral blood stem cell transplantation from double donors
      (DHSCT) has been successfully established by reducing conditioning intensity and
      increasing graft cell numbers from double haploidentical donors without GVHD
      prophylaxis. DHSCT successfully achieved stable complete chimerism, less GVHD
      morbidity and mortality and longer OS without hematopoietic suppression. This
      study provides experimental evidence for clinical application of HLA
      haploidentical peripheral blood stem cell transplantation from double donors.

PMID- 28446307
TI  - [Effect of ABO-Incompatibility on Outcome of Allogeneic Hematopoietic Stem Cell
      Transplantation].
AB  - OBJECTIVE: To investigate the effect of ABO-incompatibility on the efficacy and
      complications of allogeneic hematopoietic stem cell transplantation(HSCT).
      METHODS: The clinical data of 54 recipients who received ABO-incompatible allo
      HSCT were retrospectively analyzed and were compared with 54 ABO-identical
      recipients as controls. Hematopoietic reconstruction and the blood type
      conversion time were dynamically observed and compared between 2 groups. RESULTS:
      The time of erythrocyte reconstitution was prolonged to 24 d in ABO-incompatible
      group, compared with that of 19 d in ABO-compatible group (P<0.01). The
      difference of neutrophil and platelet reconstruction was not statistically
      significant (P>0.05). Major mismatch group and bidirectional mismatch group
      required more erythrocyte transfusions than that of ABO-compatible group. The
      surface antigen of erythrocyte change in major mismatch group was earlier than
      that of minor mismatch group (P<0.05). The incidence of cytomegalovirus (CMV)
      infection, acute graft versus host disease (aGVHD) and survival were not
      significantly different between 2 groups. CONCLUSION: ABO-incompatibility can not
      influence the effect of allo-HSCT, but ABO-incompatibility delayed erythrocyte
      recovery, and required more RBC and platelet transfusions.

PMID- 28446306
TI  - [Relationship between NK Cell Reconstitution and aGVHD after Allo-HSCT].
AB  - OBJECTIVE: To investigate the relationship between NK cell count/activity and
      acute graft-versus-host disease (aGVHD) in patients receiving allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 26
      patients who had undergone allo-HSCT from January to July 2015 were enrolled in
      this study. The NK cell count/activity in the peripheral blood of recipients on
      day 30 after allo-HSCT were monitored by using 4-color flow cytometry. The
      incidence of aGVHD in patients was evaluated by clinical manifestation
      combinating with related pathologic indicators, and the relationship between NK
      cell count/activity and aGVHD were analyzed. RESULTS: In the aGVHD group and the
      no-aGVHD group, the NK cell count and activity on days 30 after allo-HSCT were
      655+/-216 cells/ul vs 1169+/-372 cells/ul(P=0.002) and 7.3+/-3.6% vs 9.0+/-3.6%
      (P=0.008). In the II-IV grade aGVHD group and the 0-I grade aGVHD group, the NK
      cell count/activity were 617+/-220 cells/ul vs 1081+/-399 cells/ul (P=0.001) and
      4.2+/-1.7% vs 8.3+/-3.5%(P=0.001). As compared with the 0-I grade aGVHD group,
      patients in the II-IV grade aGVHD group had higher relapse rate (57% vs
      5%)(P=0.010) , lower 1-year progression-free survival(PFS) rate (43% vs
      84%)(P=0.010). CONCLUSION: NK cell count/activity on day 30 after allo-HSCT were
      closely relates with aGVHD, which may be a potential marker for aGVHD and can
      provide a new target for aGVHD therapy.

PMID- 28446308
TI  - [Effect of MicroRNA-146b-5p on Adipogenesis of Mouse Bone Essence Derived
      Mesenchymal Stem Cells].
AB  - OBJECTIVE: To explore the effect of MicroRNA-146b-5p (miR-146b-5p) on the mouse
      bone essence derived MSC adipogenic differentiation. METHODS: MSC were isolated
      from bone essence of C57BL/6 mice. The expression level of miR-146b-5p in the
      process of adipogenic differentiation of MSC was detected by q-PCR; the role of
      miR-146b-5p mimics or inhibitors in the process of mouse bone essence derived MSC
      adipogenic differentiation was analyzed through oil red staining the expression
      of C/EBPalpha and PPARgamma after cultured for 14 days was detected by q-PCR; the
      protein level of PPARgamma after miR-146b-5p transfection was detected by Western
      blot. RESULTS: The MSC were successfully isolated from bone essence of mice, the
      q-PCR results showed an increasing expression level of miR-146-5p in the process
      of MSC adipogenic differentiation. Compared with the control group, MSC
      transfected with miR-146b-5p mimic could up-regulate the expression of miR-146b
      5p (P<0.001), while miR-146b-5p inhibitor transfection could down-regulate the
      endogenous miR-146b-5p expression (P<0.01). After culture for 14 d, the result of
      Oil red staining showed that the miR-146b-5p inhibitor could inhibit adipogenic
      differentiation, while the miR-146b-5p mimic could promote the adipogenic
      differentiation of MSC. After induction for 14 d, compared with control, the
      PPARgamma and C/EBPalpha in mimic group were higher expressed PPARgamma and
      C/EBPalpha (P<0.01). Compared with induced group, the PPAPgamma and C/EBPalpha
      were lower expressed in inhibitor group (P<0.05). The results of Western blot
      showed that the expression level of PPARgamma was high in minic group, and it was
      low in inhibitor group. CONCLUSION: miR-146b-5p is up-regulated in the process of
      MSC adipogenic differentiation, and it promotes the adipogenesis of MSC
      originated from mouse bone essence.

PMID- 28446309
TI  - [Establishment of mouse stably knockout of MYSM1 in MSC cell line C3H10T1/2 and
      its effect on the immune regulation in vitro].
AB  - OBJECTIVE: To aimed at the establishment of mouse stably knockout of MYSM1
      mesenchymal stem cell(MSC) line C3H10T1/2, and to investigate its immunological
      capacity of MSC in vitro. METHODS: To establish the stably transfected MSC cell
      line by using CRISPR-Cas9 technology. Then the Flow cytometry, quantitative PCR
      and Western blot were employed to detect whether the MYSM1 have been knockout
      yet. Furthermore, the immune modulatory effect of MYSM1-/- MSC was tested by
      addition of MYSM1-/- MSC supernatant into spleen lymphocyte and Foxp3 culture.
      The mRNA expression of inflammatory cytokines such as interleukin-4, interferon
      gamma and interleukin-17 were detected by quatitatine PCR. RESULTS: The
      expression of MYSM1 was steadily knock out in MSC. In addition, MYSM1-/- MSC
      showed a stronger inhibitory effect on the expression of inflammatory cytokines.
      Therefore, the MYSM1 has been stably knocked out in C3H10T1/2. CONCLUSION: The
      mouse stably knockout of MYSM1 mesenchymal stem cells has been successfully
      established, the knock-out of MYSM1 in MSC can induce more potent
      immunosuppressive effects on cellular immune reaction in vitro. Our data laid a
      foundation for the further MSC-based applications in immune related diseases.

PMID- 28446310
TI  - [PDGF-BB Promotes CFU-GM and CFU-MK Formation and Its Possible Mechnism].
AB  - OBJECTIVE: To investigate the effect of platelet-derived growth factor (PDGF-BB)
      on the formation of granulocyte-monocyte colony forming unit (CFU-GM) and
      megakaryocyte colony forming unit (CFU-MK) and its anti-apoptotic effect on CHRF
      cells. METHODS: The CFU-GM and CFU-MK of murine and human bone marrow cells were
      cultured in vitro by using plasma clot culture system. The anti-apoptotic effect
      of PDGF-BB on CHRF cells and its mechanism were clarified by flow cytometry.
      RESULTS: PDGF-BB 0-100 ng/ml stimulated the proliferation of murine and human CFU
      GM and CFU-MK in a dose-dependent manner. The maximal stimulation effect was
      obtained at 50 ng/ml of PDGF-BB (P<0.01). Furthermore, PDGF-BB had an anti
      apoptotic effect on CHRF cells as shown by the flow cytometry with AnnexinV/PI
      double staining, Caspase-3 expression and JC-1 detection (P<0.05). CONCLUSION:
      PDGF-BB significantly stimulates the proliferation of CFU-GM and CFU-MK in vitro,
      and has an anti-apoptotic effect on CHRF cells.

PMID- 28446311
TI  - [Establishment of Double Antibody Sandwich ELISA for the Determination of Human
      Soluble VE-Cadherin in Human Plasma and Its Application].
AB  - OBJECTIVE: To establish double antibody sandwich enzyme-linked immunosorbent
      assay (ELISA) for the determination of human soluble VE-cadherin in human plasma
      and to investigate its value in clinical use. METHODS: The monoclonal antibodies
      against human VE-cadherin were prepared from BALB/c mice immunized with
      prokaryotic expression recombinant proteins, and the best combination of double
      antibodies was selected by checkerboard titration method. Double antibody
      sandwich ELISA for the determination of human VE-cadherin was established by
      using HRP-labeled McAb as a detection antibody and a capture antibody. The
      methodology performance was evaluated. The plasma concentrations of VE-cadherin
      in 28 healthy subjects and 60 patients with cancer were determined. RESULTS: The
      double antibody sandwich ELISA for the determination of human VE-cadherin was
      established by selecting the combination of double antibodies. The detection
      limit was 24.7 pg/ml, the coefficients of variation for inner-batch and inter
      batch were 4.1%-7.7% and 8.7%-10.8% respectively. The average recovery was 96.7%.
      The plasma level of soluble VE-cadherin in normal controls was 262.1+/-11.75
      pg/ml. The plasma level of soluble VE-cadherin was 173.9+/-17.98 pg/ml in 24
      patients with leukemia, 311.7+/-25.24 pg/ml in 14 patients with stomach cancer,
      206.8+/-25.01 pg/ml in 11 patients with lung cancer, and 310.7+/-11.82 pg/ml in
      others patients(9 patients with breast cancer, 1 patients with gliomas, 1
      patients with liver cancer). CONCLUSION: The developed ELISA kit has better
      sensitivity and specificity, and can be used in detection of human soluble VE
      cadherin in human plasma, therefore, it can provide a new mathod for diagnosis of
      cancer patients.

PMID- 28446312
TI  - [Clinical Characteristics and Gene Mutations of Gilbert Syndrome Complicated with
      Myeloproliferative Neoplasm].
AB  - OBJECTIVE: To investigate the clinical characteristics and gene mutations of
      patients with Gilbert syndrome complicated with myeloproliferative neoplasms
      (MPN). METHODS: Peripheral blood samples from 1 patient with Gilbert syndrome
      complicated with MPN and his son were collected to analyse all exon mutations of
      UGT1A1 gene. RESULTS: The patient with leukocytosis, thrombocythemia, mild anemia
      and positive JAK2/V617F mutation was initially diagnosed as MPN. The
      hyperbilirubinemia suggested concurrent disease. Further gene evaluation
      disclosed a insertion mutation in the (TA)6TAA box, and a missense mutation(G->A)
      at 211 bp of exon 1, corresponding to the deficiency in the bilirubin-conjugating
      enzyme uridine-diphosphoglucuronosyl transferase1A1 (UGT1A1). His son only
      carried some polymorphism mutation without manifestation of this disease.
      CONCLUSION: It is a first report case of MPN complicated with Gilbert syndrome
      that can highlight the differential diagnosis for hyperbilirubinemia.

PMID- 28446313
TI  - [Effect of Agkistrodon Acutus Venom PCA on HUVEC Activity].
AB  - OBJECTIVE: To investigate the effects of Agkistrodon acutus venom protein C
      activator(PCA) on ultrastructure of human umbilical vein endothelial
      cells(HUVEC), and the levels of tissue factor(TF), vascular von Willebrand factor
      (vWF) and endothelin-1 secreted by HUVEC and to clarify the anti-thrombotic
      mechanism of PCA. METHODS: The experiments were divided into control group(DMEM),
      LPS group (LPS 0.1 ug/ml), PCA group(PCA 1 ug/ml) and PCA+LPS group (1 ug/ml PCA+
      0.1 ug/ml LPS). The morphology of endoplasmic reticulum, mitochondria and the
      number of autophagosome in HUVEC were observed by transmission electron
      microscopy. The TF, vWF and ET-1 were measured in the medium of each group by
      ELISA; RT-PCR was used to detect mRNA expression level of vWF and ET-1 in cells;
      and the protein expression level of TF in cells was detected by Western blot.
      RESULTS: Compared with the control group, the ultrastructural changes of HUVEC in
      the LPS group included the cell membrane getting rough, swelling of mitochondria
      and endoplasmic reticulum, and autophagosome increase, however, the
      ultrastructure differences between PCA and control group were not significant.
      Compared with the ultrastructure of HUVECs in LPS group, the swelling of
      mitochondria and endoplasmic reticulum disappeared in the LPS+PCA group, and the
      number of autophagosome decreased obviously. Compared with the control group, the
      content of ET-1, vWF and TF in cell culture supernatant, and the protein
      expression level of vWF, ET-1 gene and TF protein were significantly increased in
      LPS group (P<0.05); the expression levels of the 3 factors in the cell culture
      supernatant and cells in PCA group were not significantly different from the
      control group (P>0.05). The expression levels of TF, vWF and ET-1 in LPS group
      were significantly lower than those in LPS+PCA group (P<0.05). CONCLUSION: PCA(1
      ug/ml) can reduce the ultrastructural changes of HUVEC induced by LPS, and
      inhibit the increase of TF, vWF and ET-1 secretion from HUVEC induced by LPS.

PMID- 28446314
TI  - [Changes of Neutrophil CD64 in Patients with Hematological Mali-gnancies Combined
      with Bacterial Infections].
AB  - OBJECTIVE: To explore the changes of CD64 on surface of neutrophils in patients
      with hematological malignancies combined with bacterial infections. METHODS:
      Ninety-seven patients with hematological tumor admitted in our hospital from
      August 2014 to February 2016 were selected and divided into 2 groups: infection
      group(50 cases) and noninfection group(47 cases) according to their symptoms,
      physical sings and blood culture results for microbiologic detection. The CD46
      index on surface of neutrophils, serum C- reactive protein (CRP), neutrophil
      count (NC) and procalcitonin (PCT) level were detected by flow cytometry. After
      treatment of infection patients, the CD46 index, CRP, PCT and NC were detected
      again. RESULTS: Before antibacterial treatment of patients, the CD64 index in
      infection group was significantly higher than that in noninfection group, the
      CRP, PCT and NC levels in infection group also were higher than those in
      noninfection group; after antibacterial treatment, the CD64 index, CRP, PCT and
      NC levels in infection group decresed. CONCLUSION: The CD64 index in hematologic
      malignancy patients complicated with bacterial infections significantly
      increased, after antibacterial treatment these indexes decreases, confirming the
      value of CD64 in the diagnosis of bacterial infections for patients with
      hematologic malignancies.

PMID- 28446315
TI  - [Research on Relation of Platelet Aggregation Rate with Platelet Concentration in
      Platelet-Rich Plasma'].
AB  - OBJECTIVE: To explore the effect of platelet concentration in platelet-rich
      plasma (PRP)' on platelet aggregation rate, to determine the allowed range of
      inducer adenosine diphosphate (ADP: 5.0 umol/L, ADP: 1.5 umol/L) and arachidonic
      acid (AA: 500.0 ug/ml) for platelet concentration in platelet aggregation rate.
      METHODS: The venous blood samples of 72 healthy persons with citrate
      anticoagulation were selected and divided into groups, every 12 cases were mixed
      for each group. After the samples were mixed, different levels of platelet
      concentrations were prepared, and platelet aggregation rate of 6 groups with
      different platelet concentrations by ADP and AA inducer were detected by Helena
      platelet aggregation analyzer respectively. RESULTS: When the concentration of
      the inducer increased, the platelet aggregation rate of different platelet
      concentrations increased. With the platelet concentration increased, AA and ADP
      (15 umol/L) induced platelet aggregation rate showed a rapid increase at first
      and then showed slowing, when the Plt concentration is less than 200*109/L, AA
      induced platelet aggregation rate decreased with the steep drop, and ADP induced
      platelet aggregation rate increased slightly slowly along with platelet
      concentration increasing. When platelet count lower than 200*109/L and AA 500
      ug/ml and ADP 15 umol/L were used for induction, the changes of platelet
      aggregation rate of different concentrations of platelet was slow, less volatile
      and more stable. CONCLUSION: When the platelet aggregation rate was detected, the
      appropriate platelet concentration of AA and ADP inducing agents should be
      greater than 200*109/L.

PMID- 28446316
TI  - [Prognostic Value of Recurrent Molecular Genetics and Epigenetics Abnormity in T
      Lymphoblastic Lymphoma / Leukemia -Review].
AB  - T lymphoblastic lymphoma / leukemia is a strong invasive and has a high incidence
      of various molecular genetic abnormalities. The NOTCH1 / FBXW7 mutation is one of
      the most common mutations, and related with good prognosis in T-LBL / ALL. PTEN
      mutation, a poor prognostic factor, could be overcome by NOTCH1 mutations in
      pediatric patients to some extent. Patients with MLL gene abnormality and loss of
      heterozygosity 6q have worse prognosis than those with normal karyotype. The
      incidence of MLL gene abnormality, RUNX1 mutation and DNMT3A mutation in early
      precursor T-lymphoblastic leukemia was higher than that of other mature subtypes,
      which could be used as risk stratification factors. Epigenetic abnormalities play
      an important role in the malignant transformation of stem cells. Epigenetics
      treatment such as demethylation therapy may improve the prognosis of high-risk
      patients. In this article, the NOTCH1,FBXW7,PTEN and RAS gene mutations and
      prognosis, the molecular and cellular abnormalities and prognosis, as well as
      epigenetic abnormality and prognosis are reviewed.

PMID- 28446317
TI  - [Research Progress on Relationship between CD58 Molecule and ALL and Lymphoma 
      Review].
AB  - Lymphocyte function-associated antigen-3 (LFA-3/CD58) is a cell-surface
      glycoprotein, it can bind to CD2 and activate the costimulation pathways of T
      lymphocytes and natural killer (NK) cells, maximizing the cytolysis of target
      cells by cytotoxic T lymphocytes (CTL) and NK cells. Some studies have
      demonstrated that in acute lymphoblastic leukemia(ALL) and lymphomas, lack of
      CD58 on the tumor cells may fail to activate the T lymphocytes and NK cells,
      resulting in feeble cytotoxic effect and subsequently escape from immune
      surveillance, making the disease become more complicated and liable to relapse.
      Therefore, this article aims to review the structure, biological characteristics
      of CD58 on the tumor cells and its relationship with ALL and lymphomas.

PMID- 28446318
TI  - [Research Progress of Homoharringtonine Effect on IM-resistant Chronic
      Myelogenous Leukemia -Review].
AB  - Homoharringtonine(HHT) is an alkaloid with anti-tumor activity, having a good
      therapeutic effect on chronic myeloid leukemia(CML), and its toxicity is much
      lower than other anti-cancer drugs. However, the remarkable therapeutic efficacy
      of imatinib on CML treatment made HHT to be forgotten gradually. Today, the
      omacetaxine mepesuccinate, a semisynthetic form of HHT, display a good clinical
      response to TKI-resistant CML patients. Therefore, the HHT again attracts more
      attention from the medical field. Here, the clinical effects of HHT on IM
      resistant CML patients and its mechanism are briefly reviewed.

PMID- 28446319
TI  - [Progress on Treatment of Splenic Marginal Zone Lymphoma-Review].
AB  - Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell non
      Hodgkin's lymphoma. The clinical features of SMZL are splenomegaly, lymphocytosis
      and cytopenia in peripheral blood. Immunopheno-typically, the neoplastic cells
      are typically positive for CD45, CD20, CD79a, PAX5, IgD, BCL-2. The previous
      common used treatment is splenectomy and chemotherapy. Nowadays, rituximab-based
      chemotherapy regimens has improved the curative effect dramaticlly. IFN-alpha
      with or without ribavirin can be used to treat the patients with HCV infection.
      Some new target agents such as Bruton tyrosine kinase, NOTCH inhibitor, CAL-101
      are under clinical research. This review mainly discuss the progress in the
      treatment of SMZL.

PMID- 28446320
TI  - [Advances in Diagnosis and Treatment of Primary Breast Lymphoma -Review].
AB  - Primary breast lymphoma(PBL) is a rare and unique type of lymphoma. Female
      patients are the majority, but its pathogenesis is not clear, and the estrogen
      may be related with the pathoganesis. Women who have breast implants have more
      chance to be suffered. The painless breast masses are the most common clinical
      manifestations, which is similar to breast cancer. Surgical resection of the mass
      and core needle biopsy are helpful for the diagnosis. The most common
      pathological type of PBL is diffuse large B cell type, with non GCB type, and it
      is prone to extranodal relapse in which central nervous system relapse is common
      which has poor prognosis. Therapy combined with surgery, chemotherapy and
      radiotherapy are requied, but rituximab added failed to improve its survival.
      Small molecular targeted drugs may be beneficial to PBL. In this article, the
      pathogenesis, clinical characte ristics, diagnosis and treatment of PBL are
      briefly summarized.

PMID- 28446321
TI  - [Drug-Resistant Mechanism of Multiple Myeloma and Its Therapy Combined with HDACi
      -Review].
AB  - Drug resistance of multiple myeloma(MM) has become more and more common, and
      greatly decreased the survival rate of these patients. The occurence of drug
      resistance involves in many factors such as bone marrow microenveronment, tumor
      cell self-metabolism, cytokines, specific targets and so on. In this review, the
      potential mechanisms of resistance to glucocorticoid/proteasome
      inhibitor/immunomodulatory druges are briefly expounded in the aspect of tumor
      cell self-metabolism, including the changes of heat slock protein expression,
      mRNA expression, related cytokine levels and down-regulation of thalidomid
      effecting site CRBN expression. In this review, the researches on the effect of
      histone deacetylase inhibitors(HDACi) combined with glucocorticoid, proteasome
      inhibitors, immunomodulatory drugs and monoclonal antibodies on multiple myeloma,
      specially, drug-resistant multiple myeloma are also summarized.

PMID- 28446322
TI  - [Research Advances in Treatment of Myeloma Nephropathy-Review].
AB  - Myeloma nephropathy is a common complication in patients with myltiple myeloma
      (MM) that causes high morbidity. In the majority of cases, renal impairment is
      caused by the accumulation and precipitation of light chains, which form casts in
      the distal tubules, resulting in renal obstruction. This review discusses the
      recent advances on its treatment, so as to provide reference for clinical
      treatment of MM induced-renal failure.

PMID- 28446323
TI  - [Role of Aberrant Splicing in Pathogenesis of Myelodysplastic Syndromes-Review].
AB  - The spectrum of genetic abnormalities in myelodysplastic syndromes(MDS) has been
      revealed by high-throughput sequencing. However, the functional role of these
      mutations in occurrence and development of MDS was not delineated. The mutations
      in splicing factors have been identified as the commonest gene mutations in MDS.
      Recently, it was reported that the mutated or dysregulated splicing factors,
      including SF3B1, SRSF2 and U2AF1, attribute to aberrant mRNA splicing, which
      leads to hematopoietic dysfunction and drives MDS. These findings will be of
      great help in searching for candidate therapeutic targets in mis-splicing pathway
      in MDS. In this review the role of aberrant splicing in pathogenesis of MDS is
      summarized briefly.

PMID- 28446324
TI  - [Research Advance of Microparticles in Hypercoagulation of Hemolytic Anemia
      Review].
AB  - Microparticles (MP) are small membrane vesicles released from many different cell
      types in response to cellular activation or apoptosis, which have the
      procoagulant effect. Hemolytic anemia(HA) is a type of anemia that have a short
      life expectancy of red blood cells due to the destruction which exceed the
      hematopoietic compensatory capacity of bone marrow. Sickle cell anemia(SCD),
      thalassemia and paroxysmal nocturnal hemoglobinuria(PNH) are all characterized by
      hypercoagulation and thromboembolism (TE). Research shows that MP can promote the
      formation of hypercoagulative state which in turn increases the risk of
      thromboembolism in HA. This review mainly summarized the advance research of MP
      in HA in the past 5 years. Moreover the relationship between the abnormal MP and
      hypercoagulation in HA, the impact of the related treatment to the MP, the
      research of MP in animal model of HA and the application of the MP-proteomics in
      HA are also disscussed.

PMID- 28446325
TI  - [Current Status and Future Perspectives of Primary Antifungal Prophylaxis in
      Patients with Hematological Malignancies-Review].
AB  - Invasive fungal diseases (IFD) are associated with considerable morbidity and
      mortality in patients with hematological malignancies. Primary antifungal
      prophylaxis (PAP) is effective for decreasing incidence of IFD, and the patients
      will be more tolerable to chemotherapy with less cost and better prognosis.
      Antifungal drugs as fluconazole, itraconazole, posaconazole, caspofungin and
      micafungin are all recommended for PAP by many consensus and guidelines. The PAP
      will be more scientific, appropriate and effective with the development of
      studies about predicting risk-stratification for IFD, new drugs, pharmacokinetics
      and integrated prophylaxis. This review summarizes the progress of PAP in
      hematological malignancy patients in recent years.

PMID- 28446326
TI  - [Research Progress on the Role of Musashi-2 in the Pathogenesis of Malignant
      Hematologic Diseases-Review].
AB  - Previous studies have found that Musashi-2 (Msi-2) plays an essential role in
      regulating the gene expression of stem cell populations by inhibiting or
      activating the translation, and thus regulates stem cell function. Current
      research shows that Msi-2 involved in the regulation of a variety of malignant
      hematological diseases through different mechanisms; moreover abnormally
      expressed in a variety of malignant hematological diseases and involved in the
      occurrence, development of a variety of malignant hematological diseases. Further
      study on the role of malignant hematologic diseases will further clarify the
      pathogenesis of malignant hematologic diseases, and provide a new basis for the
      diagnosis and treatment of malignant hematological diseases. In this review, the
      structure and function of Msi-2 and its relationship with malignant hematologic
      diseases and its latest research progress are summarized.

PMID- 28446327
TI  - Editorial.

PMID- 28446328
TI  - Combined GC- and UHPLC-HR-MS Based Metabolomics to Analyze Durable Anti-fungal
      Resistance Processes in Cereals.
AB  - Introduction of durable resistance genes in crops is an important strategy to
      prevent yield loss caused by pathogens. The durable multi-pathogen resistance
      gene Lr34 originating from wheat is widely used in breeding, and is functionally
      transferable to barley and rice. The molecular resistance mechanism of Lr34,
      encoding for an adenosine triphosphate-binding cassette transporter, is not known
      yet. To understand the molecular function and the defense response of durable
      disease resistance in cereals, the metabolic response of Lr34 was investigated
      in, except for the Lr34 gene, genetically identical lines of barley, rice and
      wheat. A broad range of compounds including primary, secondary and lipophilic
      metabolites were analyzed by a combination of gas (GC) and liquid chromatography
      (LC) mass spectrometry (MS) based methods. Data from metabolomics correlated well
      with transcriptomics data for plant defense responses such as the formation of
      anti-fungal hordatines or the components of the glyoxylate cycle. Induction of
      the glyoxylate cycle found in transgenic Lr34 rice grown in the greenhouse was
      confirmed in field-grown natural Lr34 wheat. Constitutively active plant defense
      responses were observed in the different cereals.

PMID- 28446329
TI  - State-of-the-art Nanofabrication in Catalysis.
AB  - We present recent developments in top-down nanofabrication that have found
      application in catalysis research. To unravel the complexity of catalytic
      systems, the design and use of models with control of size, morphology, shape and
      inter-particle distances is a necessity. The study of well-defined and ordered
      nanoparticles on a support contributes to the understanding of complex phenomena
      that govern reactions in heterogeneous and electro-catalysis. We review the
      strengths and limitations of different nanolithography methods such as electron
      beam lithography (EBL), photolithography, extreme ultraviolet (EUV) lithography
      and colloidal lithography for the creation of such highly tunable catalytic model
      systems and their applications in catalysis. Innovative strategies have enabled
      particle sizes reaching dimensions below 10 nm. It is now possible to create
      pairs of particles with distance controlled with an extremely high precision in
      the order of one nanometer. We discuss our approach to study these model systems
      at the single-particle level using X-ray absorption spectroscopy and show new
      ways to fabricate arrays of single nanoparticles or nanoparticles in pairs over a
      large area using EBL and EUV-achromatic Talbot lithography. These advancements
      have provided new insights into the active sites in metal catalysts and enhanced
      the understanding of the role of inter-particle interactions and catalyst
      supports, such as in the phenomenon of hydrogen spillover. We present a
      perspective on future directions for employing top-down nanofabrication in
      heterogeneous and electrocatalysis. The rapid development in nanofabrication and
      characterization methods will continue to have an impact on understanding of
      complex catalytic processes.

PMID- 28446330
TI  - Automated Identification of Relevant Frontier Orbitals for Chemical Compounds and
      Processes.
AB  - Quantum-chemical multi-configurational methods are required for a proper
      description of static electron correlation, a phenomenon inherent to the
      electronic structure of molecules with multiple (near-)degenerate frontier
      orbitals. Here, we review how a property of these frontier orbitals, namely the
      entanglement entropy is related to static electron correlation. A subset of
      orbitals, the so-called active orbital space is an essential ingredient for all
      multi-configurational methods. We proposed an automated selection of this active
      orbital space, that would otherwise be a tedious and error prone manual
      procedure, based on entanglement measures. Here, we extend this scheme to
      demonstrate its capability for the selection of consistent active spaces for
      several excited states and along reaction coordinates.

PMID- 28446331
TI  - Mechanistic Investigations of C-H Activations on Silica-Supported Co(ii) Sites in
      Catalytic Propane Dehydrogenation.
AB  - Catalytic reactions involving C-H bond activations are central to the chemical
      industry. One such example, alkane dehydrogenation, has recently become very
      important due to shortfalls in propene production and a large supply of cheap
      propane. However, current technologies are inefficient and have only moderate
      selectivity. In order to understand how to improve currently used catalysts, we
      must know more about the mechanism by which propane is dehydrogenated. We show
      here that Co(<small>ii</small>) sites on silica are good catalysts for the
      dehydrogenation of propane, having high activity and selectivity that is
      reasonably stable over the course of 10 h. Mechanistic investigations of this
      catalyst show that the main activation mechanism is most likely C-H activation by
      1,2 addition.

PMID- 28446332
TI  - DNA Polymerase Inhibition by High Kinetic Stability of T-HgII-T Base Pairs.
AB  - A fluorescent surrogate of thymidine called DMAT was used for the first
      fluorescence-based study of HgII binding to discrete T-T sites in duplex DNA. The
      fluorescent properties of DMAT-A base pairs were highly sensitive to wild-type T
      HgII-T base pair formation at an adjacent site, allowing for a determination of
      the precise thermodynamic and kinetic parameters of these metal binding
      reactions. T-HgII-T complexes exhibited equilibrium dissociation constants of Kd
      ~ 8-50 nM. These high-affinity binding interactions are characterized by very
      slow association and dissociation kinetics (kon ~ 104- 105 M-1s-1, koff ~ 10-4 -
      10-3s-1), revealing exceptionally high kinetic stabilities of T-HgII-T base pairs
      (half-lives = 0.3-1.3 h). Duplex DNA containing DMAT and no T-T mismatch
      exhibited nonspecific HgII binding affinities of Kd ~ 2.0 MUM. The high kinetic
      stabilities of T-HgII-T resulted in the inhibition of dynamic processes such as
      DNA strand invasion and strand displacement during enzymatic DNA synthesis, which
      led to premature chain termination. These results demonstrated that T-HgII-T base
      pairs are kinetically distinct from T-A base pairs and therefore are likely to
      disrupt DNA metabolism in vivo.

PMID- 28446333
TI  - Chiral Cyclopentadienyl Ruthenium Complexes as Versatile Catalysts for
      Enantioselective Transformations.
AB  - Ruthenium complexes, in particular cyclopentadienyl ruthenium (<small>ii</small>)
      derivatives, catalyze a vast number of transformations in the field of homogenous
      catalysis. Herein we describe the first synthesis of efficient chiral cationic
      cyclopentadienyl ruthenium (<small>ii</small>) catalysts and their application in
      enantioselective cycloisomerizations yielding 4H-pyrans. A tremendous counterion
      effect on the selectivity was observed and subsequently explored, giving rise to
      a complementary set of neutral cyclopentadienyl ruthenium (<small>ii</small>)
      complexes able to catalyze asymmetric cyclobutene formations.

PMID- 28446334
TI  - Improving Sensitivity of Solid-state NMR Spectroscopy by Rational Design of
      Polarizing Agents for Dynamic Nuclear Polarization.
AB  - We review our recent efforts to optimize the efficiency of polarizing agents for
      Dynamic Nuclear Polarization (DNP) in solid-state MAS NMR spectroscopy. We
      elucidate the links between DNP performance, molecular structure and electronic
      relaxation properties of dinitroxide biradicals. We show that deuteration and
      increased bulkiness lead to slower electronic relaxation and in turn to higher
      DNP enhancements. We also show that the incorporation of solid dielectric
      particles into the sample is a general method of amplifying DNP enhancements by
      about a factor of two.

PMID- 28446335
TI  - Quantitative Nano-characterization of Polymers Using Atomic Force Microscopy.
AB  - The present article offers an overview on the use of atomic force microscopy
      (AFM) to characterize the nanomechanical properties of polymers. AFM imaging
      reveals the conformations of polymer molecules at solid- liquid interfaces. In
      particular, for polyelectrolytes, the effect of ionic strength on the
      conformations of molecules can be studied. Examination of force versus extension
      profiles obtained using AFM-based single molecule force spectroscopy gives
      information on the entropic and enthalpic elasticities in pN to nN force range.
      In addition, single molecule force spectroscopy can be used to trigger chemical
      reactions and transitions at the molecular level when force-sensitive chemical
      units are embedded in a polymer backbone.

PMID- 28446336
TI  - Towards Cellular Activation of an Artificial Metalloenzyme: Development of an
      Artificial Zymogen.
AB  - Regulation of enzymatic activity is essential for living organisms. Nowadays,
      with the emergence of synthetic biology, there is a rising interest in placing
      the activity of synthetic catalysts under the control of a cell. This short
      review aims at summarizing the regulation strategies developed to date, and at
      presenting the development of an artificial zymogen, which is upregulated by a
      natural protease. In our view, this constitutes a first step towards the cellular
      control of the activity of an artificial metalloenzyme.

PMID- 28446337
TI  - Error Assessment of Computational Models in Chemistry.
AB  - Computational models in chemistry rely on a number of approximations. The effect
      of such approximations on observables derived from them is often unpredictable.
      Therefore, it is challenging to quantify the uncertainty of a computational
      result, which, however, is necessary to assess the suitability of a computational
      model. Common performance statistics such as the mean absolute error are prone to
      failure as they do not distinguish the explainable (systematic) part of the
      errors from their unexplainable (random) part. In this paper, we discuss problems
      and solutions for performance assessment of computational models based on several
      examples from the quantum chemistry literature. For this purpose, we elucidate
      the different sources of uncertainty, the elimination of systematic errors, and
      the combination of individual uncertainty components to the uncertainty of a
      prediction.

PMID- 28446338
TI  - CO Cleavage and CO2 Functionalization under Mild Conditions by a Multimetallic
      CsU2 Nitride Complex.
AB  - Novel efficient chemical processes involving cheap and widely accessible carbon
      dioxide or carbon monoxide under mild conditions for the production of valuable
      chemical products are highly desirable in the current energetic context. Uranium
      nitride materials act as high activity catalysts in the Haber-Bosch process but
      the reactivity of molecular nitride compounds remains unexplored. Here we review
      recent results obtained in our group showing that a multimetallic nitride complex
      [Cs{[U(OSi(OtBu)3)3]2(MU-N)}] (1) with a CsUIV-N-UIV core, is able to promote N-C
      bond formation due to its strong nucleophile behaviour. In particular, complex 1,
      in the presence of excess CO2 leads to a remarkable dicarbamate product. The
      multimetallic CsUIV-N-UIV nitride also readily cleaves the C=O bond under mild
      conditions.

PMID- 28446339
TI  - Progress in the Optimization of 4(1H)-Quinolone Derivatives as Antimalarials
      Targeting the Erythrocytic, the Exoerythrocytic and the Transmitting Stages of
      the Malaria Parasite.
AB  - Malaria is one of the leading infectious diseases occurring mainly in tropical
      and subtropical areas. Although available antimalarial tools have reduced the
      number of fatalities, there is still an urgent need for the development of new
      and more efficacious treatments to cure and eradicate malaria especially due to
      emerging resistance to all antimalarial drugs. Research was initiated to revisit
      antimalarial compounds which were deemed unsuitable as a result of poor
      understanding of physicochemical properties and the optimization thereof. The
      4(1H)-quinolones are a class of compounds with demonstrated activity against
      malaria parasites. Recent optimization of the long-known core led to two highly
      promising compounds, i.e. P4Q-391 and ELQ-300, with great selective activity
      against all stages of the parasite's life cycle and good physicochemical
      properties. In this paper, we discuss the key steps on the way to these
      compounds, which fuel hope to find a suitable treatment for the prevention, cure
      and eradication of malaria.

PMID- 28446340
TI  - Peptide Dendrimer-Lipid Conjugates as DNA and siRNA Transfection Reagents: Role
      of Charge Distribution Across Generations.
AB  - Transfection reagents are used to deliver DNA and siRNA into cells to achieve
      genetic manipulations, and may ultimately enable nonviral gene therapy. Progress
      in transfection reagents is limited by the fact that such reagents cannot be
      easily optimized due to their polymeric nature and/or difficult synthesis. We
      have developed a new class of well-defined and easily modifiable transfection
      reagents in the form of peptide dendrimers. These dendrimers self-assemble with
      DNA or siRNA and lipofectin to form nanoparticles which efficiently enter
      mammalian cells and liberate their nucleic acid cargo. By systematically
      modifying the amino acid sequence of our dendrimers we have found that their
      transfection efficiency depends on the distribution of positive charges and
      hydrophobic residues across the dendrimer branches. Positive charges present in
      all three generations lead to efficient DNA delivery, whereas siRNA delivery
      requires charges in the outer two generations combined with a hydrophobic
      dendrimer core.

PMID- 28446341
TI  - Decarboxylative Alkynylation and Cyanation of Carboxylic Acids using Photoredox
      Catalysis and Hypervalent Iodine Reagents.
AB  - Alkynes and nitriles are important functional groups that serve as versatile
      building blocks in organic synthesis and find applications in material and
      medicinal sciences. A convenient and straightforward access to both classes of
      compounds under mild conditions is, therefore, highly desirable. Herein, we
      disclose the decarboxylative alkynylation and cyanation of broadly available
      carboxylic acids using photoredox catalysis and hypervalent iodine reagents.
      Choices of both catalysts and reagents were crucial. Computational and
      experimental studies revealed two different possible mechanisms that are dictated
      by the oxidation potential of the reagents: radical for alkynylation, ionic for
      cyanation.

PMID- 28446342
TI  - Unveiling the Nature of Charge Carrier Interactions by Electroabsorption
      Spectroscopy: An Illustration with Lead-Halide Perovskites.
AB  - Unravelling the nature of the interactions between photogenerated charge carriers
      in solar energy conversion devices is key to enhance performance. In this
      perspective, we discuss electroabsorption spectroscopy (EAS), as the spectral
      bandshape of the electroabsorption (EA) signal directly depends on the strength
      of the charge carrier interactions. For instance, the electroabsorption response
      in molecular or confined excitonic systems can be modelled perturbatively
      yielding the Stark effect. In contrast, most solids exhibit weaker interactions,
      and a perturbative approach cannot be taken in general. For solids with
      negligible charge carrier interactions, one resorts to the Franz-Keldysh theory
      of a continuum in a field, that, in the low-field limit, simplifies to the low
      field FKA effect. Alternatively, when the continuum approximation breaks down,
      the problem of a Wannier exciton in a field has to be solved, and numerical
      methods emerged as the best solution. We illustrate our discussion with two
      examples involving lead-halide perovskites, a new, high-stake solar cell
      material. In the first example, we discuss the lineshape of the electroabsorption
      response for thin-films of lead-iodide perovskite, that sustains the
      photogeneration of free carriers. In the second example, we address a confined
      excitonic case with lead-bromide perovskite nanoparticles, and demonstrate the
      presence of so-called charge-transfer excitons.

PMID- 28446343
TI  - From Short Electrospun Nanofibers to Ultralight Aerogels with Tunable Pore
      Structure.
AB  - Nanofiber production by electrospinning has made great progress over the past two
      decades. Recently the research area was revolutionized by a novel post-processing
      approach. By cutting the endless and intertwined nanofibers into short pieces, it
      is now possible to reassemble them into interconnected 3D structures. Such highly
      porous structures are built from dispersed short nanofibers by freeze-casting.
      This solid templating process controls the structures' ultimate properties and
      architecture in terms of primary and secondary pores below 5 MUm and between 10
      and 300 MUm, respectively. The objective of this review is to provide insight
      into this young field of research, in particular highlighting the processing
      steps, materials and current applications, from scaffolds for tissue engineering,
      acoustics, sensors and catalyst supports to filtration.

PMID- 28446345
TI  - Multimode Separation for Metabolomics and Complex Environmental Samples.

PMID- 28446346
TI  - Engineering Nanosized Organosilica for Molecular Recognition and Biocatalysis
      Applications.
AB  - A series of synthetic nanomaterials capable of molecular recognition and/or
      biocatalysis have been produced by exploiting the self-sorting, self-assembly and
      polycondensation of organosilane building blocks around protein templates. The
      established methodology allows for the production of thin organosilica layers of
      controlled thickness, down to nanometer precision. Fully synthetic virus
      recognition materials have been shown to specifically bind their target virus
      down to picomolar concentrations. The shielding of natural enzymes allowed
      producing nanobiocatalysts functioning under harsh operational conditions.

PMID- 28446348
TI  - biotechnet Switzerland Conference Report 2016 TEDD Annual Meeting, 27. October,
      2016, ZHAW Wadenswill.

PMID- 28446350
TI  - The First Aid and Hospital Treatment of Gunshot and Blast Injuries.
AB  - BACKGROUND: When gunshot and blast injuries affect only a single person, first
      aid can always be delivered in conformity with the relevant guidelines. In
      contrast, when there is a dynamic casualty situation affecting many persons, such
      as after a terrorist attack, treatment may need to be focused on immediately life
      threatening complications. METHODS: This review is based on pertinent
      publications retrieved by a selective search in Medline and on the authors'
      clinical experience. RESULTS: In a mass-casualty event, all initial measures are
      directed toward the survival of the greatest possible number of patients, in
      accordance with the concept of "tactical abbreviated surgical care." Typical
      complications such as airway obstruction, tension pneumothorax, and hemorrhage
      must be treated within the first 10 minutes. Patients with bleeding into body
      cavities or from the trunk must be given priority in transport; hemorrhage from
      the limbs can be adequately stabilized with a tourniquet. In-hospital care must
      often be oriented to the principles of "damage control surgery," with the highest
      priority assigned to the treatment of life-threatening conditions such as
      hemodynamic instability, penetrating wounds, or overt coagulopathy. The main
      considerations in initial surgical stabilization are control of bleeding, control
      of contamination and lavage, avoidance of further consequences of injury, and
      prevention of ischemia. Depending on the resources available, a transition can be
      made afterward to individualized treatment. CONCLUSION: In mass-casualty events
      and special casualty situations, mortality can be lowered by treating immediately
      life-threatening complications as rapidly as possible. This includes the early
      identification of patients with lifethreatening hemorrhage. Advance preparation
      for the management of a masscasualty event is advisable so that the outcome can
      be as favorable as possible for all of the injured in special or tactical
      casualty situations.

PMID- 28446351
TI  - Deep Vein Thrombosis of the Upper Extremity.
AB  - BACKGROUND: Deep venous thrombosis (DVT) arises with an incidence of about 1 per
      1000 persons per year; 4-10% of all DVTs are located in an upper extremity (DVT
      UE). DVT-UE can lead to complications such as post-thrombotic syndrome and
      pulmonary embolism and carries a high mortality. METHODS: This review is based on
      pertinent literature, published from January 1980 to May 2016, that was retrieved
      by a systematic search, employing the PRISMA criteria, carried out in four
      databases: PubMed (n = 749), EMBASE (n = 789), SciSearch (n = 0), and the
      Cochrane Library (n = 12). Guidelines were included in the search. RESULTS: DVT
      UE arises mainly in patients with severe underlying diseases, especially cancer
      (odds ratio [OR] 18.1; 95% confidence interval [9.4; 35.1]). The insertion of
      venous catheters-particularly central venous catheters-also elevates the risk of
      DVT-UE. Its clinical manifestations are nonspecific. Diagnostic algorithms are of
      little use, but ultrasonography is very helpful in diagnosis. DVT-UE is treated
      by anticoagulation, with heparin at first and then with oral anticoagulants.
      Direct oral anticoagulants are now being increasingly used. The thrombus is often
      not totally eradicated. Anticoagulation is generally continued as maintenance
      treatment for 3-6 months. Interventional techniques can be used for special
      indications. Patients with DVT-UE have a high mortality, though they often die of
      their underlying diseases rather than of the DVT-UE or its complications.
      CONCLUSION: DVT of the upper extremity is becoming increasingly common, though
      still much less common than DVT of the lower extremity. The treatment of choice
      is anticoagulation, which is given analogously to that given for DVT of the lower
      extremity.

PMID- 28446353
TI  - Different Recommendations.

PMID- 28446352
TI  - Effectiveness of Pyrethrum Extracts.

PMID- 28446354
TI  - In Reply.

PMID- 28446355
TI  - The Cholesterol Embolism Syndrome.

PMID- 28446356
TI  - Constructive Dialogue Necessary.

PMID- 28446357
TI  - Environmental Diseases Are Multifactorial.

PMID- 28446358
TI  - Diagnostic Use of Chelating Agents.

PMID- 28446359
TI  - In Reply.

PMID- 28446360
TI  - Does Not Correspond to Everyday Reality.

PMID- 28446361
TI  - In Reply.

PMID- 28446362
TI  - Ovarian haemangiomas with peripheral hilus cell proliferation.

PMID- 28446363
TI  - Reassessment of lipaemic index threshold triggering high speed centrifugation of
      lipaemic specimens.

PMID- 28446364
TI  - Clinical and laboratory diagnosis of heparin induced thrombocytopenia: an update.
AB  - Heparin remains a commonly used anticoagulant in prophylaxis and treatment of
      venous and arterial thrombosis, in addition to ensuring patency of artificial
      blood circuits such as cardiopulmonary bypass (CPB). Heparin induced
      thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin
      therapy that results from production of polyclonal antibodies to heparin in
      complex, usually with platelet factor 4 (PF4). In a proportion of patients, this
      causes platelet activation and thrombin generation, which may result in
      thrombosis. However, identification of patients with HIT can be complicated as
      thrombocytopenia is common in hospitalised patients receiving heparin, and is
      usually due to other causes. Clinical assessment of the likelihood of HIT is
      paramount in order to make appropriate decisions regarding laboratory
      investigations and ongoing anticoagulation, especially given clinically expressed
      pro-thrombotic states. However, clinical assessment, on its own, cannot guarantee
      diagnosis or exclusion of HIT, and therefore is facilitated by laboratory
      testing, although unfortunately, this is frequently limited by local availability
      of assays and delay in availability of results. Nevertheless, there are an
      increasing number of available laboratory tests that can be used to identify
      antibodies causing HIT, including both immunological and functional assays. This
      narrative review will discuss the existing tools for clinical assessment in
      addition to evaluating the advantages and disadvantages of the available
      laboratory assays for HIT.

PMID- 28446365
TI  - Corrigendum to "Oldenlandia diffusa suppresses metastatic potential through
      inhibiting matrix metalloproteinase-9 and intercellular adhesion molecule-1
      expression via p38 and ERK1/2 MAPK pathways and induces apoptosis in human breast
      cancer MCF-7 cells" [J. Ethnopharmacol. 195 (2017) 309-317].

PMID- 28446366
TI  - A pro-inflammatory diet is associated with increased risk of developing
      hypertension among middle-aged women.
AB  - BACKGROUND AND AIMS: A pro-inflammatory diet is thought to lead to hypertension
      through oxidative stress and vessel wall inflammation. We therefore investigated
      the association between the dietary inflammatory index (DII) and developing
      hypertension in a population-based cohort of middle-aged women. METHODS AND
      RESULTS: The Australian Longitudinal Study on Women's Health included 7169
      Australian women, aged 52 years (SD 1 year) at baseline in 2001, who were
      followed up through 4 surveys until 2013. The DII, a literature-derived dietary
      index that has been validated against several inflammatory markers, was
      calculated based on data collected via a validated food-frequency questionnaire
      administered at baseline. Hypertension was defined as new onset of doctor
      diagnosed hypertension, ascertained through self-report between 2001 and 2013.
      Generalised Estimating Equation analyses were used to investigate the association
      between the DII and incident hypertension. The analyses were adjusted for
      demographic and hypertension risk factors. During 12-years follow-up we
      identified 1680 incident cases of hypertension. A more pro-inflammatory diet was
      associated with higher risk of hypertension in dichotomised analyses with an
      ORfully adjusted of 1.24, 95% CI: 1.06-1.45. CONCLUSION: A pro-inflammatory diet
      might lead to a higher risk of developing hypertension. These results need to be
      replicated in other studies.

PMID- 28446368
TI  - Ebola-related stigma in Ghana: Individual and community level determinants.
AB  - RATIONALE: Although Ebola-related stigmatization continues to undermine efforts
      to re-integrate survivors, few studies have examined what influences such
      stigmatizing attitudes. OBJECTIVE: This paper explores the effects of both
      individual- and community-level factors on Ebola-related stigma in Ghana.
      METHODS: Data were collected from a cross-section of 800 respondents, nested
      within 40 communities in the Greater Accra Region of Ghana. Multi-level modelling
      was employed for analysis. RESULTS: Both individual- and community-level factors
      were significant determinants of stigma. Respondents who endorsed myths about
      Ebola were significantly more likely to also endorse Ebola-related stigma.
      Similarly, those who were worried about a potential outbreak of Ebola in the
      future, had moderate risk perceptions of contracting Ebola, had primary and
      secondary education, and were not confident of the quality of health care in the
      event of an outbreak, were more likely to endorse Ebola-related stigma. Knowledge
      of Ebola was significant at the community level, but not at the individual level.
      Communities with more knowledge were less likely to endorse Ebola-related stigma.
      CONCLUSIONS: These findings underscore the need to increase the knowledge base
      while countering myths that undermine preventive behaviours to fight Ebola
      related stigma. It is equally important to adopt multi-level interventions that
      emphasize community-based strategies.

PMID- 28446367
TI  - Problematic social media use and depressive symptoms among U.S. young adults: A
      nationally-representative study.
AB  - RATIONALE: Depression is the leading cause of disability worldwide. The suggested
      association between social media use (SMU) and depression may be explained by the
      emerging maladaptive use pattern known as problematic social media use (PSMU),
      characterized by addictive components. OBJECTIVE: We aimed to assess the
      association between PSMU and depressive symptoms-controlling for overall time and
      frequency of SMU-among a large sample of U.S. young adults. METHODS: In October
      2014, participants aged 19-32 (N = 1749) were randomly selected from a nationally
      representative U.S. probability-based panel and subsequently invited to
      participate in an online survey. We assessed depressive symptoms using the
      validated Patient-Reported Outcomes Measurement Information System (PROMIS) brief
      depression scale. We measured PSMU using an adapted version of the Bergen
      Facebook Addiction Scale to encompass broader SMU. Using logistic regression
      models, we tested the association between PSMU and depressive symptoms,
      controlling for time and frequency of SMU as well as a comprehensive set of socio
      demographic covariates. RESULTS: In the multivariable model, PSMU was
      significantly associated with a 9% increase in odds of depressive symptoms (AOR
      [adjusted odds ratio] = 1.09; 95% CI [confidence interval]: 1.05, 1.13; p <
      0.001.) Increased frequency of SMU was also significantly associated with
      increased depressive symptoms, whereas SMU time was not (AOR = 1.01; 95% CI:
      1.00, 1.01; p = 0.001 and AOR = 1.00; 95% CI: 0.999-1.001; p = 0.43,
      respectively). CONCLUSION: PSMU was strongly and independently associated with
      increased depressive symptoms in this nationally-representative sample of young
      adults. PSMU largely explained the association between SMU and depressive
      symptom, suggesting that it may be how we use social media, not how much, that
      poses a risk. Intervention efforts aimed at reducing depressive symptoms, such as
      screenings for maladaptive SMU, may be most successful if they address addictive
      components and frequency-rather than time-of SMU.

PMID- 28446369
TI  - Effect of occlusal plane correction on lip cant in two-jaw orthognathic surgery -
      A three-dimensional analysis.
AB  - INTRODUCTION: The aim of the present study was to evaluate the impact of canting
      correction in occlusal plane (OP) on the change of lip cant (LC) using three
      dimensional (3D) photogrammetry in combination with cone-beam computed
      tomographic (CBCT) scans in class III asymmetric patients. MATERIALS AND METHODS:
      Fourteen asymmetric patients with exclusively skeletal class III malocclusion
      undergoing two-jaw surgery were included. All patients received 3D-photogrammetry
      and CBCT scans before (T1) and after orthognathic surgery (T2). After image
      fusion of the CBCT scans, angular correction of the occlusal plane (COP) between
      T1 and T2 was measured. Accordingly, angular correction of the lip cant (CLC) was
      analyzed after matching the preoperative 3D-photogrammetric scan to the
      postoperative. RESULTS: At the T1 stage, the canting of the OP was higher
      compared to the LC (4.95 degrees  vs. 3.77 degrees ). During T1 to T2, a
      significant angular cant correction was observed: COP (2.64 degrees , p = 0.004)
      and CLC (1.76 degrees , p = 0.01). In addition, a linear relationship between COP
      and CLC was revealed with a correlation coefficient for angular change of 0.47.
      For the linear regression COP turned out to be a predictor for CLC (B = 0.372, t
      (13) = 1.848, p = 0.089). Hence a correction of the OP of 1 degrees  resulted in
      a correction of the LC of only 0.372 degrees . DISCUSSION: The use of CBCT scans
      in combination with 3D-photogrammetry are valuable tools to accurate analyze
      canting corrections of the OP and the LC during orthognathic surgery.

PMID- 28446370
TI  - Microcarrier culture enhances osteogenic potential of human periodontal ligament
      stromal cells.
AB  - Regeneration of periodontal tissue represents a major challenge to modern tissue
      engineering, since cell-based therapies require large amounts of periodontal
      ligament stromal cells (PLSC), which can be obtained only by in vitro expansion.
      Ideally, the period of the in vitro expansion should be optimized for the
      generation of large enough numbers of pre-specified progenitor cells ready to
      contribute to the restoration of periodontal tissues. In the present study, we
      used a commercially available, three-dimensional culturing platform and alginate
      microcarrier cell culture system for the propagation of human PLSCs, which were
      derived using the explant outgrowth method. Induction of osteogenic
      differentiation resulted in rapid and robust mineralization of the extracellular
      matrix in PLSCs grown on microcarriers, but not in PLSCs grown under standard
      culture conditions. Gene expression studies revealed upregulation of osteogenesis
      related genes, BMP2, ALP, RUNX2, MSX2, cementum protein 23, bone sialoprotein,
      osteopontin and periostin, in undifferentiated and differentiating microcarrier
      cultures of PLSCs. In addition, the microcarrier culture enhanced the expression
      of beta-catenin, intermediate filament protein vimentin and focal adhesion
      proteins vinculin and paxillin. Our study shows that microcarrier culture allows
      rapid generation of large numbers of PLSCs pre-specified towards an osteogenic
      like phenotype. This method may be useful for the development of new tissue
      engineering protocols for the reconstruction of periodontal tissues.

PMID- 28446371
TI  - Beware of the toilet: The risk for a deep tissue injury during toilet sitting.
AB  - A pressure injury (PrI) compromises quality of life and can be life-threatening.
      The fundamental cause of PrIs is sustained deformations in weight-bearing soft
      tissues, e.g., during prolonged sitting on inadequate surfaces such as a toilet
      seat. In nursing homes and geriatric facilities, patients need assistance using
      the restroom, and patients being left on the toilet for tens-of-minutes is a real
      world scenario, unfortunately. Nevertheless, there are no published studies
      regarding sustained tissue loads during toilet sitting and their effects on
      tissue physiology. Here, the biomechanical and microcirculatory responses of the
      buttock tissues to toilet sitting were investigated using finite element modeling
      and cutaneous hemodynamic measurements, to explore the potential etiology of PrIs
      occurring on the toilet. We found that prolonged sitting on toilet seats involves
      a potential risk for PrI development, the extent of which is affected by the seat
      design. Additionally, we found that specialized toilet seat cushions are able to
      reduce this risk, by lowering instantaneous tissue exposures to internal stresses
      (by up to 88%) and maintaining reduced interface pressures. Furthermore,
      hemodynamic variables were altered during the toilet sitting; in particular,
      tcPO2 was decreased by 49% +/- 7% (44 +/- 2[mmHg] to 22 +/- 4[mmHg]) during
      sitting. The current study confirms that investing in expensive PrI prevention
      (PIP) products is likely to be ineffective for an immobilized patient who is left
      to sit on a bare toilet seat for long times. This argument highlights the need
      for a holistic-care approach, employing PIP devices that span across the entire
      environment where bodyweight forces apply to tissues.

PMID- 28446372
TI  - Prosthetic valve endocarditis caused by Bartonella henselae presenting as
      recurrent fever and imitating granulomatosis with polyangiitis.

PMID- 28446373
TI  - Duplicated internal auditory canal with inner ear malformation: Case report and
      literature review.
AB  - Internal auditory canal anomalies are rare. Narrow internal auditory canal is
      believed to occur as a result of aplasia or hypoplasia of the vestibulocochlear
      nerve. Narrow duplication of the internal auditory canal is considered to be very
      rare. Narrow duplication of the internal auditory canal with inner ear
      malformation has been reported in only 3 cases. We present 2 cases of narrow
      duplication of the internal auditory canal with inner ear malformation. The first
      case had inner ear malformation on only one side and the second case had inner
      ear malformation on both sides. The embryogenesis may be different between
      internal auditory canal and inner ear.

PMID- 28446374
TI  - Emergency practice, acute low back pain, and chiropractic manipulation.

PMID- 28446375
TI  - Giant lipoma extending into two thigh canals: A case report.
AB  - Giant lipomas, although rare, represent a real diagnostic and therapeutic
      challenge. We report an unusual giant lipoma of the thigh extending into two
      thigh canals and it's diagnostic and therapeutic processes.

PMID- 28446376
TI  - Comparison of virtual reality exergaming and home exercise programs in patients
      with subacromial impingement syndrome and scapular dyskinesis: Short term effect.
AB  - OBJECTIVE: The aim of this study was to compare the short term effects of home
      exercise program and virtual reality exergaming in patients with subacromial
      impingement syndrome (SAIS). METHODS: A total of 30 patients with SAIS were
      randomized into two groups which are Home Exercise Program (EX Group) (mean age:
      40.6 +/- 11.7 years) and Virtual Reality Exergaming Program (WII Group) (mean
      age: 40.33 +/- 13.2 years). Subjects were assessed at the first session, at the
      end of the treatment (6 weeks) and at 1 month follow-up. The groups were assessed
      and compared with Visual Analogue Scale (based on rest, activity and night pain),
      Neer and Hawkins Tests, Scapular Retraction Test (SRT), Scapular Assistance Test
      (SAT), Lateral Scapular Slide Test (LSST) and shoulder disability (Shoulder Pain
      and Disability Index (SPADI)). RESULTS: Intensity of pain was significantly
      decreased in both groups with the treatment (p < 0.05). The WII Group had
      significantly better results for all Neer test, SRT and SAT than the EX Group (p
      < 0.05). CONCLUSION: Virtual reality exergaming programs with these programs were
      found more effective than home exercise programs at short term in subjects with
      SAIS. LEVEL OF EVIDENCE: Level I, Therapeutic study.

PMID- 28446377
TI  - External closed-circuit cooling system for management of patients after device
      implantation: A feasibility study.
AB  - BACKGROUND: In the first 24h after pacemaker or implantable
      cardioverter/defibrillator (ICD) implantation or replacement, the occurrence of
      hematoma and pain in the surgically treated region is not infrequent and may
      result in re-intervention and/or more severe complications, such as infections.
      Currently, the post-implant phase management is very empiric. The aim of this
      study was to test the clinical applicability and usefulness of an external close
      circuit cooling system for the management of the early post-implant period in
      patients with high risk of hematoma due to anticoagulant and/or antiplatelet
      therapy. METHODS: We studied 135 patients (78M; 71+/-11years) with high risk of
      hematoma occurrence after pace-maker (63 patients) or ICD (72 patients)
      implantation or replacement. Immediately after the intervention, a closed-circuit
      cooling system (CAREPACETM system, Zamar, Italy) was externally applied on the
      pre-pectoral region to each patient and maintained for 24h. The system has a
      compressive pad and a refrigerating circuit in which non-toxic glycolic fluid is
      pumped. The fluid temperature was set and kept at 5 degrees C for the whole
      period. RESULTS: The compressive and cooling effect of the system was well
      tolerated by all the patients at the temperature set. Four patients complained of
      noise due to machine operation, but in none the treatment was interrupted. The
      average length of hospital stay was 2.8+/-0.4days. No clinically significant
      hematoma was observed at discharge and after one month follow-up visit.
      CONCLUSIONS: This new system can be used for the management of the early phase
      after device implantation or replacement and appears clinically useful and well
      tolerated. Further studies on a larger scale are needed to test the potential
      reduction of post-intervention complications and the cost-effectiveness of this
      device.

PMID- 28446378
TI  - Ceftriaxone susceptibility and molecular characteristics of Neisseria gonorrhoeae
      isolates in Changsha, China.
AB  - A total of 128 Neisseria gonorrhoeae isolates were consecutively obtained in
      Changsha, China, between April 2015 and June 2016. The minimum inhibitory
      concentrations (MICs) of ceftriaxone were measured by agar dilution method for
      each isolate. Ceftriaxone resistance determinants involving penA, mtrR, porB and
      ponA were amplified by PCR, and the PCR products were sequenced. N. gonorrhoeae
      multi-antigen sequence typing (NG-MAST) was conducted for genotyping. The results
      exhibited 11% (14/128) of isolates were reduced susceptibility or resistant to
      ceftriaxone. One isolate with a susceptibility MIC of 0.03 mg/L harbored a penA
      mosaic allele. PBP2 A501V/T or P551S and the PorB1b G120K/A121D mutations were
      predominant in the 14 decreased susceptible or resistant isolates. Among the 128
      isolates, 31 sequence types (STs) were identified, and the most prevalent STs
      were STnew1 (n = 40), ST5061 (n = 25) and ST9176 (n = 18). The 14 decreased
      susceptible or resistant isolates were resolved into 9 STs, displaying
      considerable diversity. The results of ceftriaxone susceptibility testing
      indicated that ceftriaxone can continue to be recommended as the first-line drug
      for gonorrhea treatment in Changsha; however, it is important to maintain
      promptly surveillance for antimicrobial resistance (AMR). Non-mosaic penA alleles
      with A501V/T, P551S, and porB1b mutations may contribute to ceftriaxone
      resistance or decreased susceptibility among N. gonorrhoeae in this area, and
      heterogenous STs in these isolates excluded the clonal expansion for a particular
      subtype.

PMID- 28446380
TI  - CPAP adherence: intensive strategies may be necessary.

PMID- 28446379
TI  - Group A rotavirus genotypes in hospital-acquired gastroenteritis in Italy, 2012
      14.
AB  - BACKGROUND: Group A rotaviruses (RVA) are the leading cause of acute
      gastroenteritis (AGE) in young (aged <5 years) children, causing ~250,000 deaths
      worldwide, mostly in developing countries. Differences on nucleotide sequences of
      VP7 (G-type) and VP4 (P-type) genes are the basis for the binary RVA
      nomenclature. Although at least 32 G-types and 47 P-types of rotavirus are
      presently known, most RVA infections in humans worldwide are related to five
      major G/P combinations: G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]. AIM: To
      provide the hospitals of the Italian surveillance network with update information
      on RVA AGE. METHODS: During RVA gastroenteritis surveillance in Italy in 2012-14,
      a total of 2341 RVA-positive faecal samples were collected from children
      hospitalized with AGE, and RVA strains were genotyped following standard
      EuroRotaNet protocols. FINDINGS: Most strains analysed belonged to the five major
      human genotypes and 118 out of 2341 (5.0%) were reported to be hospital-acquired.
      Comparison of the distributions of the RVA genotypes circulating in the community
      or associated with nosocomial infections showed a different distribution of
      genotypes circulating inside the hospital wards, with respect to those observed
      in the community. G1P[8] and G9P[8] RVA strains were detected frequently, whereas
      G12P[8] caused a single large nosocomial outbreak. CONCLUSION: The information
      from this study will be useful to implement guidelines for preventing RVA AGE and
      optimizing the management of patients in hospital wards.

PMID- 28446381
TI  - Evidence-Based Practice: Research Opportunities.

PMID- 28446382
TI  - Compensatory mechanisms activated with intermittent energy restriction: A
      randomized control trial.
AB  - BACKGROUND & AIMS: Strong compensatory responses, with reduced resting metabolic
      rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated
      when weight loss (WL) is achieved with continuous energy restriction (CER), which
      try to restore energy balance. Intermittent energy restriction (IER), where short
      spells of energy restriction are interspaced by periods of habitual energy
      intake, may offer some protection in minimizing those responses. We aimed to
      compare the effect of IER versus CER on body composition and the compensatory
      responses induced by WL. METHODS: 35 adults (age: 39 +/- 9 y) with obesity (BMI:
      36 +/- 4 kg/m2) were randomized to lose a similar weight with an IER (N = 18) or
      a CER (N = 17) diet over a 12 week period. Macronutrient composition and overall
      energy restriction (33% reduction) were similar between groups. Body
      weight/composition, RMR, fasting respiratory quotient (RQ), ExEff (10, 25, and 50
      W), subjective appetite ratings (hunger, fullness, desire to eat, and prospective
      food consumption (PFC)), and appetite-regulating hormones (active ghrelin (AG),
      cholecystokinin (CCK), total peptide YY (PYY), active glucagon-like peptide-1
      (GLP-1), and insulin) were measured before and after WL. RESULTS: Changes in body
      weight (~12.5% WL) and composition were similar in both groups. Fasting RQ and
      ExEff at 10 W increased in both groups. Losing weight, either by IER or CER
      dieting, did not induce significant changes in subjective appetite ratings. RMR
      decreased and ExEff at 25 and 50 W increased (P < 0.001 for all) in IER group
      only. Basal and postprandial AG increased (P < 0.05) in IER group, whereas basal
      active GLP-1 decreased (P = 0.033) in CER group only. Postprandial CCK decreased
      in both groups (P = 0.0012 and P = 0.009 for IER and CER groups, respectively).
      No between group differences were apparent for any of the outcomes. CONCLUSIONS:
      The technique used to achieve energy restriction, whether it is continuous or
      intermittent, does not appear to modulate the compensatory mechanisms activated
      by weight loss. CLINICAL TRIAL REGISTRATION NUMBER: NCT02169778 (the study was
      registered in clinicaltrial.gov).

PMID- 28446383
TI  - Development and validation of the Parenteral Nutrition Impact Questionnaire
      (PNIQ), a patient-centric outcome measure for Home Parenteral Nutrition.
AB  - BACKGROUND & AIMS: Patients with Type 3 Intestinal Failure (IF) who need Home
      Parenteral Nutrition (HPN) face several clinical, psychological and social
      problems. The study was designed to produce and test the first patient-centric
      measure for HPN ('PNIQ: Parenteral Nutrition Impact Questionnaire'). The new
      measure focused on the extent to which patients were able to fulfil their human
      needs. METHODS: Questionnaire content was derived from the analysis of
      transcripts of interviews conducted with UK HPN patients. Cognitive debriefing
      interviews (CDIs) were performed to ensure patients found the draft scale clear,
      relevant and accessible. Finally, a test--retest postal validation survey was
      conducted to reduce the number of items in the scale and to ensure that; it was
      unidimensional, reproducible and had construct validity. RESULTS: The 30
      interview transcripts were analysed to identify issues related to a wide range of
      needs. Fifteen CDIs showed that patients found the draft scale easy to complete
      and highly relevant. The postal survey included 233 patients on HPN recruited
      through two IF units. Items were rejected if they did not fit the Rasch model,
      had too similar content to other items or displayed differential item functioning
      related to age, gender or underlying mechanism of IF. A 20-item unidimensional
      scale was identified with high internal consistency (0.91) and test-retest
      reliability (0.92). Scores on PNIQ correlated moderately highly with social
      isolation, emotional reactions and energy level and were related to perceived
      interference on life of HPN. The underlying cause of IF did not influence the way
      the scale worked. CONCLUSIONS: The PNIQ is a scientifically rigorous,
      unidimensional outcome measure that provides a complete assessment of the effect
      of HPN on everyday life. It will prove useful for measuring patient value in
      clinical practice and for determining outcome in clinical trials, audit, economic
      evaluations and outcomes-based reimbursement.

PMID- 28446384
TI  - The Directorate-General for Health and Consumers 1999-2014: An assessment of its
      functional capacities.
AB  - Capacity assessment has become a popular measure in the health sector to assess
      the ability of various stakeholders to pursue agreed activities. The European
      Commission (EC) is increasingly dealing with a variety of health issues to
      coordinate and complement national health policies. This study analyses the
      functional capacity of the Directorate-General for Health and Consumers (DG
      SANCO) between 1999 and 2004. It applies the UNDP Capacity Assessment Framework
      and uses a literature review, a document review of EU policy documents and expert
      interviews to assess the capacity of DG SANCO to fulfill its mandate for public
      health and health systems. Our results suggest that DG SANCO has established
      capacities to engage with stakeholders; to assess various health issues, to
      define issue-specific health policies and to collect information for evaluative
      purposes. In contrast, capacities tend to be less established for defining a
      clear strategy for the overall sector, for setting priorities and for budgeting,
      managing and implementing policies. We conclude that improvements to the
      effectiveness of DG SANTE's (the successor of DG SANCO) policies can be made
      within the existing mandate. A priority setting exercise may be conducted to
      limit the number of pursued actions to those with the greatest European added
      value within DG SANTE's responsibilities.

PMID- 28446385
TI  - You Never Work Alone: The Potential of Quality Improvement Research.

PMID- 28446386
TI  - Caffeine citrate - Is it a silver bullet in neonatology?
AB  - Caffeine citrate is one of the most prescribed drug in the present day NICU for
      apnea. Its efficacy, tolerability, wide therapeutic index and safety margin has
      made it the drug of choice among the methylxanthines. Its therapeutic uses in
      apnea of prematurity, mechanical ventilation, bronchopulmonary dysplasia has made
      it a "silver bullet" in neonatology. However, there are still controversies
      surrounding this drug. This review is aimed to update the reader about the basic
      pharmacology, current therapeutic uses, adverse effects, controversies as well as
      present and future research of caffeine.

PMID- 28446387
TI  - Risk factors for persistent methicillin-resistant Staphylococcus aureus infection
      in cystic fibrosis.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an
      important pathogen in cystic fibrosis (CF). Over 25% of individuals in the United
      States with CF are found to have MRSA in respiratory culture specimens, and
      persistent MRSA infection has been associated with more rapid decline in lung
      function and increased mortality. The objective of this study was to investigate
      clinical and demographic characteristics that are associated with the development
      of persistent MRSA infection in a CF population. METHODS: This was a
      retrospective cohort study of individuals followed from 2002 to 2012 in the
      Cystic Fibrosis Foundation Patient Registry. A time-to-event analysis for the
      development of persistent MRSA infection was performed, and multivariable Cox
      proportional hazards models were constructed to identify risk factors for
      infection. RESULTS: The study cohort included 19,434 individuals, of which 5844
      would develop persistent MRSA infection. In the adjusted model, pancreatic
      insufficiency (HR: 1.49; 95% CI: 1.29-1.72), CF related diabetes (HR: 1.13; 95%
      CI: 1.05-1.20), co-infection with P. aeruginosa (HR: 1.21; 95% CI: 1.13-1.28),
      and number of hospitalizations/year (HR: 1.09; 95% CI: 1.06-1.12) were all
      associated with increased risk, whereas higher socio-economic status (HR: 0.87;
      95% CI: 0.82-0.93) was associated with a lower risk. Receiving care at a CF
      center with increased MRSA prevalence was associated with increased risk of MRSA
      infection: highest quartile (HR: 2.33; 95% CI: 2.13-2.56). CONCLUSIONS: No easily
      modifiable risk factors for persistent MRSA were identified in this study.
      However, several risk factors for patients at higher risk for persistent MRSA
      infection were identified, for example centers with a high baseline MRSA
      prevalence, and may be useful in designing center-specific MRSA infection
      prevention and control strategies and/or eradication protocols. Additional
      studies are needed in order to evaluate if attention to these risk factors can
      improve clinical outcomes.

PMID- 28446388
TI  - Medial shoe-ground pressure and specific running injuries: A 1-year prospective
      cohort study.
AB  - OBJECTIVES: Achilles tendinitis, plantar fasciopathy and medial tibial stress
      syndrome injuries (APM-injuries) account for approximately 25% of the total
      number of running injuries amongst recreational runners. Reports on the
      association between static foot pronation and APM-injuries are contradictory.
      Possibly, dynamic measures of pronation may display a stronger relationship with
      the risk of APM-injuries. Therefore, the purpose of the present study was to
      investigate if running distance until the first APM-injury was dependent on the
      foot balance during stance phase in recreational male runners. DESIGN:
      Prospective cohort study. METHODS: Foot balance for both feet was measured during
      treadmill running at the fastest possible 5000-m running pace in 79 healthy
      recreational male runners. Foot balance was calculated by dividing the average of
      medial pressure with the average of lateral pressure. Foot balance was
      categorized into those which presented a higher lateral shod pressure (LP) than
      medial pressure, and those which presented a higher medial shod pressure (MP)
      than lateral pressure during the stance phase. A time-to-event model was used to
      compare differences in incidence between foot balance groups. RESULTS: Compared
      with the LP-group (n=59), the proportion of APM-injuries was greater in the MP
      group (n=99) after 1500km of running, resulting in a cumulative risk difference
      of 16%-points (95% CI=3%-point; 28%-point, p=0.011). CONCLUSIONS: Runners
      displaying a more medial pressure during stance phase at baseline sustained a
      greater amount of APM-injuries compared to those displaying a lateral shod
      pressure during stance phase. Prospective studies including a greater amount of
      runners are needed to confirm this relationship.

PMID- 28446390
TI  - Natriuretic peptides: degradation, circulating forms, dosages and new therapeutic
      approaches.
AB  - Testing for natriuretic peptides (BNP, NT-proBNP or MR-proANP) is recommended by
      the European Society of Cardiology (ESC) since 2005 for the exclusion diagnosis
      of acute and chronic heart failure because of very high predictive values.
      Natriuretic peptides are produced by the heart in response to high transmural
      pressure and/or myocardial ischemia. These peptides circulate in blood of both
      healthy subjects and heart failure patients. Mass spectrometry methods allowed
      identifying a collection of circulating and degraded forms of BNP, NT-proBNP and
      proBNP. Glycosylated forms of NT-proBNP and proBNP have also been identified.
      Current immunoassays are lacking analytical specificity due to high cross
      reactivities between circulating forms. Moreover, glycosylation has been found to
      interfere with the capacity of antibodies to bind correctly to analytes. These
      elements have been taken into account to propose strategies for the development
      of new standardized and improved immunoassays. More recently, the better
      understanding of the degradation pathways of natriuretic peptides allowed the
      raise of new therapeutic approaches for heart failure patients. All these
      elements are detailed in this review.

PMID- 28446391
TI  - [Effect of intermittent fasting on physiology and gut microbiota in presenium
      rats].
AB  - OBJECTIVE: To investigate the effect of intermittent fasting on metabolize and
      gut microbiota in obese presenium rats fed with high-fat-sugar-diet. METHODS: We
      fed the Wistar rats with high-fat and high-sugar diet to induce adiposity, and
      the rats for intermittent fasting were selected base on their body weight. The
      rats were subjected to fasting for 72 h every 2 weeks for 18 weeks. OGTT test was
      performed and fasting blood samples and fecal samples were collected for
      measurement of TC, TG, HDL-C and LDL-C and sequence analysis of fecal 16S rRNA V4
      tags using Illumina. Gut microbial community structure was analyzed with QIIME
      and LEfSe. RESULTS: After the intervention, the body weight of the fasting rats
      was significantly lower than that in high-fat diet group (P<0.01). OGTT results
      suggested impairment of sugar tolerance in the fasting group, which showed a
      significantly larger AUC than compared with the high-fat diet group (P<0.05).
      Intermittent fasting significantly reduced blood HDL-C and LDL-C levels (P<0.05)
      and partially restored liver steatosis, and improved the gut microbiota by
      increasing the abundance of YS2, RF32 and Helicobacteraceae and reducing
      Lactobacillus, Roseburia, Erysipelotrichaceae and Ralstonia. Bradyrhizobiaceae
      was found to be positively correlated with CHOL and HDL-C, and RF39 was inversely
      correlated with the weight of the rats. CONCLUSION: Intermittent fasting can
      decrease the body weight and blood lipid levels and restore normal gut microbiota
      but can cause impairment of glucose metabolism in obese presenium rats.

PMID- 28446392
TI  - [Effect of HBP-A on meniscal injury and pathological hypertrophy and
      calcification of the meniscus].
AB  - OBJECTIVE: To investigate the effect of HBP-A on meniscal injuries and the
      expressions of genes associated with pathological hypertrophy and calcification
      of the meniscusinduced by abnormal loading. METHODS: Bovine meniscus explants
      were subjected to 25% strain at 0.3 Hz for 3 h and treated with 0.6 mg/mL of HBP
      A. The cell viability in the meniscus explants after 72 hin culture was
      determined using live/dead staining and the expression levels of genes associated
      with pathological hypertrophy and calcification of the meniscus (ANKH, ENPP1,
      ALP, MMP13, and IL-1) were measured using real-time PCR and Western blotting. The
      conditioned medium was collected for testing sulfated glycosaminoglycan (GAG)
      release. RESULTS: The number of dead cells, loss of proteoglycan content, and the
      expressions of ANKH, ENPP1, ALP and MMP13, and IL-1 at both the mRNA and protein
      levels were all significantly lower in the meniscus explants treated with 0.6
      mg/mL HBP-A than in the explants with only 25% abnormal pressure stimulation
      (n=3, P<0.05). CONCLUSION: HBP-A can effectively alleviate meniscal injuries
      induced by abnormal loading and suppress the expressions of genes related with
      pathological hypertrophy and calcification of the meniscus, and can serve as a
      potential drug for treatment of knee osteoarthritis.

PMID- 28446393
TI  - [Lowered sarcoendoplasmic reticulum calcium uptake and diaphragmatic SERCA1
      expression contribute to diaphragmatic contractile and relaxation dysfunction in
      septic rats].
AB  - OBJECTIVE: The explore the mechanism responsible for diaphragmatic contractile
      and relaxation dysfunction in a rat model of sepsis. METHODS: Thirty-six adult
      male Sprague-Dawley rats were randomized equally into a sham-operated group and
      two model groups of sepsis induced by cecal ligation and puncture (CLP) for
      examination at 6 and 12 h following CLP (CLP-6 h and CLP-12 h groups). The
      parameters of diaphragm contractile and relaxation were measured, and the calcium
      uptake and release rates of the diaphragmatic sarcoendoplasmic reticulum (SR) and
      the protein expressions of SERCA1, SERCA2 and RyR in the diaphragmatic muscles
      were determined. RESULTS: The half-relaxation time of the diaphragm was extended
      in both the CLP-6 h and CLP-12 h groups with significantly reduced maximum
      tension declinerate and the peek uptake rate of SERCA (P<0.01). Diaphragmatic
      maximum twitch force development rate, the maximal twitch, tetanus tensions and
      the peek release rate of SR decreased only at 12h after CLP (P<0.01). The
      expression levels of SERCA1 protein decreased significantly in the diaphragmatic
      muscles at 12h following CLP (P<0.01) while SERCA2 expression level and SERCA
      activity showed no significant changes. CONCLUSION: In the acute stage of sepsis,
      both the contractile and relaxation functions of the diaphragm are impaired.
      Diaphragmatic relaxation dysfunction may result from reduced calcium uptake in
      the SR and a decreased level of SERCA1 in the diaphragmatic muscles.

PMID- 28446394
TI  - [Expressions of OCT4, Notch1 and DLL4 and their clinical implications in
      epithelial ovarian cancer].
AB  - OBJECTIVE: To investigate the correlations among OCT4, Notch1 and DLL4 and their
      association with the clinicopathological features of patients with epithelial
      ovarian cancer (EOC). METHODS: A total of 207 specimens of EOC and 65 specimens
      of benign ovarian epithelial tumor tissues were examined for expressions of OCT4,
      Notch1 and DLL4 proteins using immunohistochemistry. RESULTS: The positivity
      rates of OCT4, Notch1 and DLL4 in EOC tissues were 60.0%, 61.8% and 60.9%,
      respectively, significantly higher than the rates in benign epithelial tumor
      tissues (9.2%, 6.2%, and 0, respectively; P<0.05). The expressions of OCT4,
      Notch1 and DLL4 in EOC were significantly correlated with tumor differentiation,
      FIGO stage, and lymph node metastasis (P<0.05). DLL4 was positively correlated
      with OCT4 and Notch1 expressions (r=0.758 and 0.704, respectively, P<0.001), and
      the latter two were also positively correlated (r=0.645, P<0.001).
      Overexpressions of OCT4, Notch1 and DLL4 were associated with a poor prognosis,
      and the survival rate was significantly lower in patients positive for OCT4,
      Notch1, and DLL4 than in the negative patients (P<0.05). FIGO stage and
      expressions of OCT4 and DLL4 were independent prognostic factors of EOC (P<0.05).
      CONCLUSION: The expressions of OCT4, Notch1 and DLL4 are correlated with the
      differentiation, lymph node metastasis, clinical stage and prognosis of EOC.
      Combined detection of the 3 proteins has an important value in predicting the
      progression and prognosis of EOC.

PMID- 28446395
TI  - [Effect of inhibiting TIM-4 function in Kupffer cells on liver graft rejection in
      mice].
AB  - OBJECTIVE: To investigate the effects of inhibiting TIM-4 function in Kupffer
      cells (KCs) on liver graft rejection in mice and explore the underlying
      mechanism. METHODS: Mouse models of orthotopic liver transplantation were treated
      with a control mAb group and TIM-4 mAb. The activated KCs were assayed with
      immunohistochemistry after operation. The expression of TIM-4 in KCs were assayed
      with Western blotting and RT-PCR and the levels of AST, ALT, TBIL, TNF-alpha, IFN
      gamma and CCL2 were assayed detected. The expression of TIM-4 in KCs was observed
      with laser confocal microscopy. HE staining was used to observe the
      microstructure of the liver tissues, and the number of CD25+Foxp3+T cells was
      determined using with flow cytometry; the proteins levels of p-P65and p-P38 were
      assayed with Western blotting. The donor mice were treated with clodronate
      liposomes to destroy the KCs in the liver before transplantation, and the liver
      grafts were examined for graft rejection. RESULTS: The number of activated KCs in
      the liver graft increased progressively over time. Compared with the sham
      operated group, the liver graft showed significantly increased TIM-4 protein and
      mRNA levels at 1, 3, and 7 days after transplantation (P<0.05) and increased
      levels of AST, ALT, TBIL, TNF-alpha, IFN-gamma and CCL2 at 7 days (P<0.05). The
      graft in TIM-4 mAb group showed mild pathological changes with a mean RAI score
      of 2.67?0.75, which was significantly lower than that in control mAb group
      (P<0.05). The mean survival time of the recipient mice was 53.8?6.4 days in TIM-4
      mAb group, significantly longer than that in the control mAB group (14.5?2.9
      days, P<0.05). Donor treatment with clodronate liposomes resulted in comparable
      RAI scores in TIM-4 mAb and control mAb groups (8.01?0.64 vs 7.93?0.56, P>0.05).
      The protein levels of p-P65 and p-P38 in TIM-4 mAb group were significantly lower
      than those in control mAb group (P<0.05), and CD25+Foxp3+T cells in the liver
      graft increased significantly in TIM-4 mAb group. CONCLUSION: Inhibition of TIM-4
      function in KCs reduces the production of inflammatory factors after liver
      transplantation possibly by inhibiting the NF-kappaB and MAPK signaling pathways
      and promoting the proliferation of Foxp3+Treg cells to induce allograft
      tolerance.

PMID- 28446397
TI  - [Expression of asparagine synthetase in relapsed or refractory extranodal NK/T
      cell lymphoma].
AB  - OBJECTIVE: To detect the expression level of asparagine synthetase (ASNS) in
      patients with relapsed or refractory extranodal NK/T cell lymphoma and explore
      its clinical significance. METHODS: Ten patients with relapsed or refractory
      extranodal NK/T cell lymphoma admitted in our department from January, 2013 to
      January, 2016 were analyzed. The diagnoses were confirmed by pathological and
      immunohistochemical examination following failed chemotherapies in all cases.
      Branched DNA-liquidchip technique (bDNA-LCT) was used for detecting ASNS mRNA
      expression in paraffin-embedded tissue sections in the 10 cases of relapsed or
      refractory extranodal NK/T cell lymphoma and in 5 cases of chronic rhinitis. The
      correlations were analyzed between ASNS expression and the clinicopathological
      features and outcomes of the patients with failed chemotherapy regimens
      containing asparaginasum. RESULTS: Six out of the 10 patients with relapsed or
      refractory extranodal NK/T cell lymphoma died due to diseaseprogression. The
      expression level of ASNS was significantly higher in the lymphoma tissues than in
      tissue specimens of chronic rhinitis (P<0.05). The expression level of ASNS was
      associated with the International Prognostic Index (P=0.023) in patients with
      relapsed or refractory extranodal NK/T cell lymphoma, and Kaplan-Meier curve
      showed that a high ASNS expression was correlated with a reduced overall survival
      and progression-free survival of the patients. CONCLUSION: Asparaginasum-based
      chemotherapy regimens are recommended for treatment of relapsed or refractory
      extranodal NK/T cell lymphoma with low ASNS expressions.

PMID- 28446396
TI  - [Application of thoracic paravertebral nerve block in video-assisted thoracosopic
      surgery: a randomized controlled trial].
AB  - OBJECTIVE: To investigate the effect of a single dose of ropivacaine combined
      with sufentanilfor thoracic paravertebral block (TPVB) on pain and enhanced
      recovery after surgery (ERAS) in patients undergoing video-assisted thoracosopic
      surgery. METHODS: Sixty patients undergoing video-assisted thoracosopic surgery
      were randomly divided into three groups to receive intravenous combined general
      anesthesia (group C), a single dose of ropivacainefor thoracic paravertebral
      block before surgery combined with intravenous and general anesthesia(group T1),
      or a single dose of ropivacaineand sufentanilfor thoracic paravertebral
      blockcombined with intravenous and general anesthesia (group T2). None of the
      patients used postoperative analgesia pump, and tramadol hydrochoride injection
      (100 mg) was given in cases with NRS scores > 4 after the surgery. The data were
      recorded including analgesics used for nerve block before the operation,
      intravenous dosage of sufentanilduring operation, total dose of sufentanilused
      (intravenous+nerve block), intravenous remifentanil dose during operation, NRS
      scores at 4, 6, 24, 48 h after the surgery, rescue analgesia in the first
      postoperative 24 h after surgery, ICU stay and hospital stay after the surgery.
      RESULTS: Compared with those in group C, the intravenous sufentanildose, total
      sufentanildose, intravenous remifentanildose during operation, NRS scores at 4
      and 6, 24 h, and ICU stay and hospital stay after the surgery were significantly
      decreased in groups T1 and T2 (P<0.05). The total dose of opioids during the
      operation and NRS scores at 4 and 6 h were significantly lower in group T2 than
      in group T1 (P<0.05), but the total dose of sufentanil, ICU stay and hospital
      stay were simialr between the two groups. CONCLUSION: A single dose of
      ropivacaine combined with sufentanilfor thoracic paravertebral blockbefore
      surgery can reduce the total dose opioids, produce the optimal analgesic effect,
      and promote postoperative recovery of the patients.

PMID- 28446398
TI  - [Sinogram restoration for low-dose cerebral perfusion CT images].
AB  - OBJECTIVE: In clinical cerebral perfusion CT examination, repeated scanning the
      region of interest in the cine mode increases the radiation dose of the patients,
      while decreasing the radiation dose by lowering the scanning current results in
      poor image quality and affects the clinical diagnosis. We propose a penalized
      weighted least-square (PWLS) method for recovering the projection data to improve
      the quality of low-dose cerebral perfusion CT imaged. This method incorporates
      the statistical distribution characteristics of brain perfusion CT projection
      data and uses the statistical properties of the projection data for modeling. The
      PWLS method was used to recover the data, and the Gauss-Seidel (GS) method was
      employed for iterative solving. Adaptive weighting is introduced between the
      original projection data and the projection data after PWLS restoration. The
      experimental results on the clinical data demonstrated that the PWLS-based
      sinogram restoration method improved noise reduction and artifact suppression as
      compared with the conventional noise reduction methods, and better retained the
      edges and details to generate better cerebral perfusion maps.

PMID- 28446400
TI  - [Risk factors of pain during colonoscopic examination].
AB  - OBJECTIVE: To investigate the risk factorsthat predict pain during colonoscopy
      for decision of sedation or analgesia before the examination. METHODS: A total of
      283 consecutive patients undergoing colonoscopicexamination at Nanfang Hospital
      between July, 2016 and September, 2016were retrospectively analyzed. The clinical
      data and visual analogue scale after the examination were analyzed to identify
      the risk factors for pain during colonoscopy using univariate analysis and
      multivariate logistic regression. A risk stratification model for predicting pain
      in colonoscopy was established. RESULTS: The completion rate of the procedure was
      significantly lower in patients with a visual analogue scale >=5 (P<0.000).
      Univariate analysis showed that female patients, previous abdominal surgery, no
      previous experience with colonoscopy, complaint of abdominal pain before
      colonoscopy, insufficient experience of the endoscopists, patient's anticipation
      of high painlevelbefore examination, and a low body mass index (BMI) were all
      associated with the experience of pain in colonoscopy (P<0.05). Multivariate
      logistic regressionanalysis identified BMI index (X1), level of experience of the
      endoscopist (A1, A2, A3) and the patient's anticipation of painlevel (X2) as the
      risk factors of pain in colonoscopy(P<0.05), and the establishedmodel with the 3
      variables was: P=eY/(1+eY),Y=0.049-0.124*X1-0.97*X2+1.713*A1+0.781*A2+0.147*A3,
      which showed a sensitivity of 70.3% and a specificity of 67.5%for predicting pain
      in colonoscopy. CONCLUSION: The patient's anticipation of a high pain level in
      colonoscopy, insufficient experience of the endoscopist, and a low BMI are the
      independent risk factors for pain in colonoscopy, and evaluation of these factors
      can help in the decision-making concerning the use of sedation or analgesia
      before colonoscopy.

PMID- 28446399
TI  - [Inhibiting HSP70 expression enhances cisplatin sensitivity of cervical cancer
      cells].
AB  - OBJECTIVE: To investigate the relationship between sensitivity to cisplatin (DDP)
      and the expression of HSP70 in cervical cancer cells in vitro. METHODS: Cervical
      cancer Hela229 cells treated with different concentrations of DDP and the HSP70
      inhibitor (PFT-u) were examined for cell viability using MTT assay and colony
      forming ability. The cell apoptosis was analyzed by flow cytometry with propidium
      iodide staining and DAPI staining, and JC-1 staining was used to determine
      mitochondrial membrane potential. The expressions of HSP70, Bcl-2, Bax and
      caspase-3 were measured with Western blotting. A nude mouse model bearing Hela229
      cell xenograft was used to evaluate the effect of DDP and PFT-u on tumor growth.
      RESULTS: Hela229 cells expressed a higher level of HSP70 than normal cervical
      cells. The combined use of PFT-u significantly enhanced the inhibitory effect of
      DDP (P<0.01) and increased the cell apoptosis in Hela229 cells. JC-1 staining
      demonstrated that DDP combined with PFT-u more obviously reduced mitochondrial
      membrane potential. DDP combined with PFT-u more strongly lowered Bcl-2
      expression and increased the expressions of casepase-3 and Bax than DDP alone. In
      the nude mouse model, PFT-u significantly enhanced DDP sensitivity of Hela229
      cell xenografts (P<0.01). CONCLUSIONS: Inhibition of HSP70 expression can enhance
      the sensitivity of cervical cancer cell to DDP both in vivo and in vitro possibly
      by promoting cell apoptosis, suggesting the potential of HSP70 as a new target
      for gene therapy of cervical cancer.

PMID- 28446401
TI  - [Expressions of MAP2K4 and estrogen receptor and their clinical significance in
      invasive breast cancer].
AB  - OBJECTIVE: To explore the association of mitogen-activated protein kinase kinase
      4 (MAP2K4) with the pathological features, prognosis and expression of estrogen
      receptor (ER) in patients with breast cancer. METHODS: The expression of MAP2K4
      was detected immunohistochemically in 102 breast cancer tissues. Chi square test
      was used to analyze the correlation of MAP2K4 expression with the
      clinicopathological features of the patients. Kaplan-Meier and log rank test were
      used for survival analysis of the patients. Multivariate survival analysis was
      performed using Cox proportional hazard regression model. The correlation between
      the expressionsof MAP2K4 and ER was investigated using Spearman rank correlation
      test. RESULTS: Immunohistochemical analysis revealed low MAP2K4 expression in
      55.9%(57/102) and high MAP2K4 expression in 44.1%(45/102) of the breast cancer
      tissues. The expression of MAP2K4 was significantly correlated with the
      pathological grades of breast cancer (P=0.011). Kaplan-Meier survival analysis
      showed that patients with a high expression of MAP2K4 had a shorter overall
      survival rate than those with low MAP2K4 expressions (P=0.009). Multivariate
      analysis identified high expression of MAP2K4 as the independent predictor of a
      poor outcome of patients with breast cancer. The expressions of MAP2K4 and ER
      were not significantly correlated, but ER-negative patients with a high MAP2K4
      expressionshowed the shortest overall survival time. CONCLUSION: Overexpression
      of MAP2K4 promotes the progression in breast cancer and is associated with a poor
      outcome of the patients. TheER-negativepatients with a high MAP2K4 expression
      have the shortest overall survival time, suggestingthe value of combined
      examination of MAP2K4 and ER in accurate estimation of the prognosis of breast
      cancer patients.

PMID- 28446402
TI  - [Role of interleukin-17 in alveolar fluid clearance in mice with acute lung
      injury].
AB  - OBJECTIVE: To investigate the role of interleukin-17 (IL-17) in alveolar fluid
      clearance in mice with acute lung injury (ALI) and explore the possible
      mechanism. METHODS: Sixteen IL-17-knockout mice and 16 wild-type mice were both
      randomized for intratracheal instillation of PBS (control) on lipopolysaccharide
      (LPS) to induce ALI. Forty-eight hours after the treatments, the wet-dry ratio
      (W/D) of the lungs, IL-8 in the bronchoalveolar lavage fluid (BALF) and
      histopathological changes of the lung tissues were examined. The expressions of
      epithelial sodium channel alpha subunit (alpha-ENaC) was detected with Western
      blotting and liver kinase B1 (LKB1) was detected with immunohistochemistry.
      RESULTS: Compared with wild-type mice treated with LPS, IL-17 knockout mice
      showed significantly decreased W/D of the lungs (9.739?3.3 vs 5.351?0.56) and IL
      8 level in the BALF (67.50?7.33 vs 41.00?3.16 pg/mL) following LPS challenge.
      Pathological examination revealed reduced alveolar edema fluid aggregations and
      lower lung injury score in IL-17 knockout mice with also higher expression levels
      of ENaC and LKB1 compared with the wild-type mice. CONCLUSION: Knocking out IL-17
      in mice not only alleviates inflammation of the lung tissue following ALI but
      also reduces the loss of ENaC protein and promotes alveolar fluid clearance,
      mechanism of which is probably associated with LKB1.

PMID- 28446403
TI  - [Reliability and validity of Meaningful Life Measure-Chinese Revised in Chinese
      college students].
AB  - OBJECTIVE: To test the reliability and validity of Meaningful Life Measure
      Chinese Revised (MLM-CR) in Chinese college students. METHODS: A total of 1035
      college students were evaluated with MLM-CR, Satisfaction with Life Scale (SWLS),
      Purpose in Life (PIL) and Patient Health Questionnaire-2 (PHQ-2), and 120 of the
      students were examined with PIL-SF twice. RESULTS: All the items in MLM-CR had
      good discrimination indexes (r=0.753-0.838, P<0.001). Confirmatory factor
      analysis confirmed the hypothesized five-factor model of MLM-CR (Chi2/df=3.4,
      GFI=0.946, AGFI=0.924, RMR=0.069, NFI=0.953, CFI=0.966, RMSEA=0.048). The total
      internal consistency reliability of MLM-CR was 0.942, and the alpha coefficients
      of the 5 dimensions ranged from 0.782 to 0.877; the total split-half reliability
      was 0.920, and the split-half reliability of the 5 dimensions ranged from 0.752
      to 0.830; the total test-retest reliability was 0.871, and the test-retest
      reliability of the 5 dimensions ranged from 0.783 to 0.805. The criterion
      validity of MLM-CR in correlation with SWLS, PIL and PHQ-2 was 0.66, 0.755 and 
      0.388, respectively (P<0.01). The Average score of MLM-CR of the college students
      was 5.20?0.90, and the scores were significantly higher in female students than
      in the male students (P<0.001). CONCLUSION: MLM-CR has good psychometric
      properties for application in comprehensive evaluation of personal meaning in
      life.

PMID- 28446404
TI  - [Irbesartan ameliorates cardiac inflammation in type 2 diabetic db/db mice].
AB  - OBJECTIVE: To investigate the protective effects of irbesartan against cardiac
      inflammation associated with diabetes and obesity in the db/db mouse model of
      type 2 diabetes and explore the underlying mechanisms. METHODS: Twenty- four 10
      week-old diabetic db/db mice were equally randomized into irbesartan treatment
      (50 mg/kg per day) group and model group, using 12 nondiabetic littermates (db/+)
      as the controls, The mice were treated with irbesartan or saline vehicle for 16
      consecutive weeks, after which the heart pathology was observed and the heart
      weight, body weight, and serum levels of fasting blood glucose (FBG), total
      cholesterol(TC), and triglycerides(TG) were measured. The expression of nuclear
      factor-kappaB (NF-kappaB) p65 in the myocardium was assessed with
      immunohistochemistry, the protein levels of P-IkappaBalpha ,IkappaBalpha and beta
      actin were analyzed with Western blotting, and the pro-inflammatory cytokines IL
      6 and TNF-alpha mRNA were detected using quantitative real-time PCR (qPCR).
      RESULTS: Compared with db/+ mice, the saline-treated db/db mice developed
      obesity, hyperglycemia and hyperlipidemia (P<0.01). Histopathological examination
      of the heart tissue revealed inflammatory cell infiltration, increased myocardial
      interstitium and disorders of myocardial fiber arrangement. The diabetic mice
      showed increased P-IalphaBalpha and decreased IkappaBalpha protein levels,
      enhanced activity and expression of NF-kappaB in the hearts, and increased mRNA
      expression of IL-6 and TNF-alpha in the myocardium. These abnormalities were all
      associated with increased inflammatory response. Treatment with irbesartan
      improved the heart architecture and attenuated high glucose-induced inflammation
      in the diabetic mice. CONCLUSION: Treatment with irbesartan attenuates cardiac
      inflammation in type 2 diabetic db/db mice, and this effect was probably
      associated with the suppression of cardiac angiotensin II and NF-kappaB signaling
      pathway.

PMID- 28446405
TI  - [Pregnancy and obstetric outcomes of elective single versus double cleavage-stage
      embryo transfer].
AB  - OBJECTIVE: To compare the pregnancy and obstetric outcomes in elective single
      versus two cleavage-stage embryo transfer. METHODS: Fresh cleavage-stage embryo
      transfer cycles between January, 2014 and October, 2015 were reviewed, including
      39 single embryo transfer (eSET) cycles and 200 double embryo transfer (DET)
      cycles. The clinical pregnancy rates, implantation rates, multiple pregnancy
      rates, live birth rate, and obstetric outcomes (gestational age, preterm delivery
      rate and mean birth weight) were compared between the two groups. RESULTS: The
      baseline characteristics were comparable between the two groups. The estradiol
      level on the day of trigger and the oocyte number were significantly higher in
      eSET group than in DET group (10654.4 pmol/L vs 8284.2 pmol/L and 8.4 vs 7.0,
      respectively). No significant difference was found in the pregnancy rate (56.4%
      vs 66.0%) or live birth rate (48.7% vs 51.5%) between the two groups, and their
      implantation rates differed significantly (56.4% vs 37.8%). No multiple
      pregnancies occurred in eSET group while the rate of multiple pregnancies was
      22.7% in DET group. The gestational age and mean birth weight were significantly
      higher in eSET group (P<0.05), and the preterm delivery rate after DET was nearly
      three times of that after eSET, although this difference was not statistically
      significant. CONCLUSIONS: Elective single embryo transfer can be performed
      without compromising the live birth rates. Multiple pregnancy rates can be
      significantly reduced with eSET, which also results in a higher chance of
      delivering a term singleton live birth compared with DET.

PMID- 28446406
TI  - [Magnetic resonance imaging characteristics of unilateral versus bilateral
      intraplaque hemorrhage in patients with carotid atherosclerotic plaques].
AB  - OBJECTIVE: To investigate the difference in the vulnerability of carotid
      atherosclerotic plaques in patients with unilateral and bilateral intraplaque
      hemorrhage (IPH). METHODS: A retrospective analysis was conducted among 44
      patients with unilateral IPH (30 cases) or bilateral IPH (14 cases) in the
      carotid plaques detected by magnetic resonance imaging (MRI) in our hospital
      between December, 2009 and December, 2012. The age, maximum wall thickness and
      incidence of fibrous cap rupture were compared between the two groups. RESULTS:
      Compared with those with unilateral IPH, the patients with bilateral IPHs had a
      significantly younger age (66.6?9.4 years vs 73.7?9.0 years, P=0.027), a
      significantly greater maximum plaque thickness (6.3?1.9 mm vs 5.0?1.3 mm,
      P=0.035) and a higher incidence of ulcers (50% vs 13.3%, P=0.025). Logistic
      regression analysis revealed a significant association between bilateral IPHs and
      the occurrence of ulcer with an odd ratio (OR) of 6.5 (95% confidence interval
      [CI]: 1.5-28.7, P=0.014). After adjustment for gender in Model 1, bilateral IPHs
      were still significantly associated with presence of ulcer (OR=5.7, 95%CI: 1.1
      29.2, P=0.036). But after adjustment for age (P=0.131) or maximum plaque
      thickness (P=0.139) in model 2, no significant correlation was found between
      bilateral IPHs and the presence of ulcer. CONCLUSION: Compared with patients with
      unilateral IPH, those with bilateral IPHs are at a younger age and have a greater
      plaque burden and a higher incidence of fibrous cap rupture, suggesting a greater
      vulnerability of the carotid plaques in patients with bilateral IPHs.

PMID- 28446407
TI  - [Value of urgent colonoscopy in diagnosis of severe acute lower gastrointestinal
      bleeding in patients with different bowel cleanliness].
AB  - OBJECTIVE: To investigate the value of urgent colonoscopy in the diagnosis of
      severe acute lower gastrointestinal bleeding and the optimal bowel preparation
      before examination. METHODS: The clinical data were collected from 188 patients
      undergoing wither urgent or elective colonoscopy for severe acute lower
      gastrointestinal bleeding in Nanfang Hospital. Univariate analysis was used to
      assess the effect of the timing of colonoscopy on the diagnostic rate of
      hemorrhage, and a multivariate model which stratified bowel cleanliness was used
      to analyze the impact of bowel cleanliness on the diagnostic rate of urgent
      colonoscopy. RESULTS: Of the 188 patients, 118 underwent urgent colonoscopy and
      70 underwent elective colonoscopy examinations. The diagnostic rates were
      comparable between the two groups (44.1% vs 41.4%, P=0.724), but urgent
      colonoscopy resulted in a significantly higher diagnostic rate for identifying
      the bleeding source (32.2% vs 18.6%, P=0.041). The proportion of the patients
      taking oral laxatives was significantly lower in urgent colonoscopy group
      (P<0.001). Oral laxatives versus enema resulted in good, moderate, and poor bowel
      cleanliness in 63.6% vs 13.5%, 28.6% vs 24.3%, and 7.8% vs 62.2% of the patients
      (P<0.001). Univariate analysis indicated that good bowel cleanliness was
      associated with a significantly higher diagnostic rate of colonoscopy than poor
      bowel cleanliness (P=0.012). Multivariate analysis showed that with good bowel
      cleanliness, urgent colonoscopy yielded a significantly higher diagnostic rate
      than elective colonoscopy (P=0.030); subgroup analyses suggested that good bowel
      cleanliness improved the diagnostic rate of urgent colonoscopy as compared with
      poor bowel cleanliness (P=0.015). CONCLUSION: In patients with good bowel
      cleanliness, urgent colonoscopy yields a higher diagnostic rate than elective
      colonoscopy for severe acute lower gastrointestinal bleeding. Poor bowel
      cleanliness resulting from bowel preparation by enema significantly lowers the
      diagnostic performance of urgent colonoscopy. Oral laxatives are recommended over
      enemas for bowel preparation before urgent colonoscopy when the patients have
      stable hemodynamics.

PMID- 28446408
TI  - [Clinicopathological analysis of pulmonary vascular disease in 38 neonates died
      of respiratory failure].
AB  - OBJECTIVE: We reviewed the data of 38 neonates who died of respiratory failure.
      Paraffin sections of the autopsy lung samples were examined with HE staining or
      immunolabeling for CD34, CD68 and CK to observe the development of the pulmonary
      vessels and detect potential pulmonary vascular diseases (PVDs). Five cases were
      identified to have PVDs, including pulmonary hypertensive vascular remodeling in
      3 cases and alveolar capillary dysplasia in 2 cases. The result indicated that
      PVD was one of the important reasons for respiratory failure in these neonates.

PMID- 28446409
TI  - [Evaluation of PFA P2Y assay in monitoring platelet function in elderly patients
      with cardiovascular disease receiving clopidogrel treatment].
AB  - OBJECTIVE: To evaluate the value of a new platelet function test PFA P2Y (PFA
      200) in monitoring clopidogrel treatment for cardiovascular disease in elderly
      patients. METHODS: Fifty-six elderly patients receiving clopidogrel therapy in
      the Department of Cardiology of General Hospital of PLA from March to August in
      2016 and 85 healthy volunteers were recruited for analysis. All the subjects
      underwent PFA P2Y, LTA (light transmittance aggregometry) and TEG
      (Thromboelastograph) tests, and Spearman correlation coefficients were used to
      test the associations between test results. The agreement among the 3 platelet
      function test methods was assessed using Cohen's kappa coefficient. RESULTS:
      Correlation coefficient (r) was -0.701 (P<0.001) between PFA P2Y and LTA, and
      0.475 (P<0.001) between PFA P2Y and TEG. The agreement was 75% between PFA P2Y
      and LTA and 67.9% between PFA P2Y and TEG. The kappa value was 0.434 (P=0.001)
      between PFA P2Y and LTA and 0.242 (P=0.046) between PFA P2Y and TEG. With ADP
      induced maximum platelet aggregation rate of LTA >50% as the laboratory
      clopidogrel resistance, the cut-off value of PFA P2Y was 119 s (AUC=0.733) with a
      sensitivity of 75.6% and a specificity of 73.3%. CONCLUSION: PFA P2Y has a
      moderate correlation and agreement with LTA, but has a poor correlation and
      agreement with TEG. PFA P2Y can be useful for assessing the effects of
      clopidogrel therapy and the association of the cut-off value (119 s) with the
      long-term clinical ischemic events needs be confirmed in further study.

PMID- 28446410
TI  - [Mechanism of heat shock protein 90 for regulating 26S proteasome in
      hyperthermia].
AB  - OBJECTIVE: To investigate the mechanism by which heat shock protein 90 (HSP90)
      regulates 26S proteasome in hyperthermia. METHODS: Hyperthermic HepG2 cell models
      established by exposure of the cells to 42 degrees celsius; for 3, 6, 12, and 24
      h were examined for production of reactive oxygen species (ROS) and cell
      proliferation, and the changes in Hsp90alpha and 26S proteasome were analyzed.
      RESULTS: ROS production in the cells increased significantly after hyperthermia
      (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as
      the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated
      Hsp90alpha but decreased the expression level (F=164.174, P<0.001) and activity
      (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small
      interfering RNA targeting Hsp90alpha also showed significantly decreased
      expression of 26S proteasome (F=180.231, P<0.001). CONCLUSION: The intracellular
      ROS production increases as the hyperthermia time extends. Heat stress and ROS
      together cause protein denature, leading to increased HSP90 consumption and
      further to HSP90 deficiency for maintaining 26S proteasome assembly and
      stability. The accumulation of denatured protein causes unfolded protein reaction
      in the cells to eventually result in cell death.

PMID- 28446411
TI  - [Correlation between serum adiponectin level and cognitive function in patients
      with Alzheimer's disease].
AB  - OBJECTIVE: To investigate serum adiponectin level in patients with Alzheimer's
      disease (AD) and its correlation with the patients' cognitive function. METHODS:
      This case-control study was conducted in 90 patients with a highly probable
      diagnosis ofAD, who were divided into mild, moderate and severe group saccording
      to the MMSE score. Ninety healthy subjects matched for age and gender with the AD
      patients were selected as the control group. The serum levels ofadiponectin in
      the participants were detected using enzyme-linked immunosorbent assay. RESULTS:
      Serum adiponectin level was significantly lower in the AD group than in the
      control group (P<0.05). Of the 3 subgroups of the AD patients, the moderate and
      severe AD groups showed significantly lower serum adiponectin level sthan the
      control group (P<0.05), but the difference in adiponectin levels was not
      significant between the mild AD group and the control group (P>0.05); serum
      adiponectin levels also differed significantly among the 3 subgroups of AD
      patients (P<0.05). Serum adiponectin level was positively correlated with the
      MMSE score in the AD patients (r=0.683, P<0.001). CONCLUSION: Serum adiponectin
      levels are reduced in AD patients and associated with the degree of cognitive
      impairment.

PMID- 28446412
TI  - [Postoperative changes of Th17/Treg balance in patients with intracranial
      aneurysm rupture].
AB  - OBJECTIVE: To observe the dynamic changes of Th17/Treg balance in patients
      following surgical intervention for intracranial aneurysm rupture. METHODS: The
      percentage of Th cells and the intracellular IL-17 level, Treg cell percentage
      and transforming growth factor -beta1 (TGF-beta1) levels were examined in 73
      patients with rupture of aneurysms before and at 24 h, 72 h and 1 week after
      operation, with 62 patients with unruptured aneurysms and 65 healthy volunteers
      as the control. The correlations among the immune cells, cytokines and clinical
      characteristics of the patients (NIHSS, ADL and hospitalization stay) were
      analyzed. RESULTS: Th17 percentage and intracellular IL-17 levels were
      significantly higher in the patients with ruptured and unruptured aneurysms than
      in the healthy volunteers, and were significantly higher in patients with
      ruptured aneurysms than in those with unruptured aneurysms. Treg cell percentage
      and TGF-beta1 level were significantly lower in patients with aneurysms than in
      the healthy volunteers, and were lower in patients with ruptured aneurysms than
      in those with uruptured aneurysms (P<0.05). Patients with intracranial aneurysm
      rupture showed significantly increased Th17 cell percentage and IL-17 level but
      significantly lowered Treg cell percentage and TGF-beta1 at 24 h following the
      surgery (P<0.05); these changes were reversed significantly at 72 h and 1 week
      after the surgery. Th17 cell percentage and IL-17 level were positively
      correlated with NIHSS and the length of postoperative hospital stay but inversely
      correlated with ADL; Treg cell percentage and TGF-beta1 were inversely correlated
      with NIHSS and hospital stay but positively with ADL (P<0.05). CONCLUSION: In
      patients with intracranial aneurysms, the systemic immune inflammatory response
      is highlighted by excessive Th17 cells and insufficient Treg cells, which are
      closely related with the outcomes of the patients following surgical
      intervention. Evaluation of Th17/Treg balance and the cytokine levels can help to
      assess the prognosis of patients with aneurysm rupture.

PMID- 28446413
TI  - [Effects of recombinant human erythropoietin on brain-derived neurotrophic factor
      expression in different brain regions of aging rats].
AB  - OBJECTIVE: To explore the effect of recombinant human erythropoietin (rhEPO) on
      expression of brain-derived neurotrophic factor (BDNF) in different brain regions
      of aging rats. METHODS: Forty male SD rats were randomized equally into negative
      control group, D-galactose group, EPO treatment group, and positive control
      group. Rat models of subacute aging were established by continuous subcutaneous
      injection of 5% D-galactose. Immunohistochemical staining was used to analyze the
      variation of BDNF expressions in different brain regions of the aging rats with
      different treatments. RESULTS: Significant brain region-specific differences in
      BDNF expression were found among the rats in different groups. Compared with
      those in the negative control group, the numbers of BDNF-positive cells in the
      hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were
      all decreased obviously in D-galactose group (P<0.05) but increased in both EPO
      group and the positive control group (P<0.05) without significant differences
      between the latter two groups. In the rats in the same group, the number of BDNF
      positive cells varied markedly in different brain regions (P<0.05), and the
      expression level of BDNF was the highest in the frontal cortex followed by the
      hippocampal CA3 region and the dentate gyrus, and was the lowest in the
      hippocampal CA1 region. CONCLUSION: Treatment with rhEPO enhances the expression
      of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system
      from aging by regulating the BDNF pathway.

PMID- 28446414
TI  - [Efficiency of 27-plex single nucleotide polymorphism multiplex system for
      ancestry inference in different populations].
AB  - OBJECTIVE: To validate the efficiency of 27-plex single nucleotide polymorphism
      (SNP) multiplex system for ancestry inference. METHODS: The 27-plex SNP system
      was validated for its sensitivity and species specificity. A total of 533 samples
      were collected from African, Southern Chinese Han, China's ethic minorities (Yi,
      Hui, Miao, Tibet, and Uygur), European, Central Asian, Western Asian, Southern
      Asian, Southeast Asian and South American populations for clustering analysis of
      the genotypes by citing 3 representative continental ancestral groups [East Asia
      (CHB), Europe (CEU), and Africa (YRI)] from HapMap database. RESULTS: The system
      sensitivity is 0.125 ng. Twenty and six genotypes were detected in chimpanzee and
      monkeys, respectively. Except in rs10496971, no more products were found in other
      animals. The system was capable of differentiating intercontinental populations
      but not of distinguishing between East Asian and Southeast Asian population or
      between Southern Chinese Han population and Chinese Ethnic populations (Hui,
      Miao, Yi and Tibet). This system achieved a 100% accuracy for intercontinental
      population source inference for 46 blind test samples. CONCLUSION: 27-plex SNPs
      multiplex system has a high sensitivity and species specificity and can correctly
      differentiate the ancestry origins of individuals from African, European and East
      Asian for criminal case investigation. But this system is not capable of
      distinguishing subpopulation groups and more specific ancestry-informative
      markers are needed to improve its recognition of Southeast Asian and Chinese
      ethnic populations.

PMID- 28446415
TI  - [Expressions of inflammatory and fibrogenic factors in perinephric and
      subcutaneous adipose tissues of patients with adrenocorticotropic hormone
      independent Cushing's syndrome].
AB  - OBJECTIVE: To investigate the expressions of inflammation- and fibrosis-related
      genes in perinephric and subcutaneous adipose tissues in patients with
      adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. METHODS: The
      perinephric and subcutaneous adipose tissues adipose tissues were obtained from 8
      patients with ACTH-independent Cushing's syndrome undergoing laparoscopic
      retroperitoneal adrenalectomy. Real-time PCR was used to detect the mRNA
      expression levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF
      alpha), matrix metallopeptidase 2 (MMP-2), TIMP metallopeptidase inhibitor 1
      (TIMP-1), early growth response 1 (EGR1), CCAAT/enhancer binding protein
      beta(CEBPbeta), uncoupling protein 1(UCP-1), PPARgamma coactivator 1 alpha
      (PGC1alpha) and cell death-inducing DFFA-like effector a (CIDEA). RESULTS: The
      mRNA level of CIDEA was significantly higher in the perinephric adipose tissue
      (peri-N) than in the subcutaneous adipose tissue (subQ) (P<0.05). The expressions
      of CEBPbeta, UCP-1, and PGC1alpha mRNA in the peri-N were similar with those in
      the subQ. The expressions of IL-6, TIMP1 and EGR1 mRNA in the subQ were
      significantly higher than those in the peri-N (P<0.05). No significant difference
      in TNF-alpha and MMP-2 mRNA levels was found between peri-N and subQ. CONCLUSION:
      The expression levels of the inflammation- and fibrosis-related genes are higher
      in the subQ than in the peri-N of patients with ACTH-independent Cushing's
      syndrome, suggesting that chronic exposure to endogenous hypercortisolism may
      cause adipose tissue dysfunction.

PMID- 28446416
TI  - [Research progress of depression and the application of esketamine].
AB  - OBJECTIVE: The pathogenesis and etiology of still remain unknown. Current
      evidence suggests that the occurrence of depression may be related to a reduced
      secretion of neurotransmitters, neuronal apoptosis, inflammation, intestinal
      flora and other factors. Although the commonly used antidepressants such as
      SSRIs, SNRIs, NaSSA, and SARIs produce some therapeutic effects, they fail to
      relieve the full spectrum of the symptoms of depression. In recent years,
      esketamine was found to produce a potent and a long-lasting antidepressant effect
      by acting on the NMDA receptors. Herein the authors review the progress in the
      study of the pathogenesis and drug therapies of depression, the efficacy of
      esketamine treatment and the underlying mechanism, and the prospect of esketamine
      treatment. Currently the mechanism of the antidepressant effect of esketamine
      remains indeterminate and its clinical application is limited, but its effect in
      rapidly alleviating the symptoms of depression suggests its bright prospect for
      clinical applications.

PMID- 28446417
TI  - The Value of Vestibular Rehabilitation in Patients with Bilateral Vestibular
      Dysfunction.
AB  - OBJECTIVE: The value of vestibular rehabilitation in patients with bilateral
      vestibular dysfunction was investigated. MATERIALS AND METHODS: This study
      assessed 17 patients (9 males, 8 females) with bilateral vestibular dysfunction.
      Vestibular rehabilitation continued for 1.5 months. Videonystagmography tests
      (including oculomotor testing, positional testing, and caloric tests), vestibular
      evoked myogenic potential (VEMP) testing, and computerized dynamic posturography
      were performed during the pre-, mid-, and post-treatment periods. The patients
      underwent cranial and internal acoustic canal MRI. Consultant physicians from the
      neurology and physical medicine and rehabilitation departments reviewed all
      patients. RESULTS: The post-treatment anteroposterior somatosensorial (APSO),
      anteroposterior global (APGLO), mediolateral visual (MLVI), and mediolateral
      global values and anteroposterior and mediolateral trials and conditions were
      significantly higher than those measured in the pre-treatment period. Similarly,
      mid-treatment values of the APSO, APGLO, and the anteroposterior sensory
      organization test (SOT) 2 were significantly higher than those measured in the
      pre-treatment period. CONCLUSION: Vestibular rehabilitation was effective in
      patients with bilateral vestibular dysfunction. As the vestibular rehabilitation
      duration increased, so did the efficacy of the treatment.

PMID- 28446418
TI  - Compliance With Mobile Ecological Momentary Assessment Protocols in Children and
      Adolescents: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Mobile device-based ecological momentary assessment (mobile-EMA) is
      increasingly used to collect participants' data in real-time and in context.
      Although EMA offers methodological advantages, these advantages can be diminished
      by participant noncompliance. However, evidence on how well participants comply
      with mobile-EMA protocols and how study design factors associated with
      participant compliance is limited, especially in the youth literature. OBJECTIVE:
      To systematically and meta-analytically examine youth's compliance to mobile-EMA
      protocols and moderators of participant compliance in clinical and nonclinical
      settings. METHODS: Studies using mobile devices to collect EMA data among youth
      (age <=18 years old) were identified. A systematic review was conducted to
      describe the characteristics of mobile-EMA protocols and author-reported factors
      associated with compliance. Random effects meta-analyses were conducted to
      estimate the overall compliance across studies and to explore factors associated
      with differences in youths' compliance. RESULTS: This review included 42 unique
      studies that assessed behaviors, subjective experiences, and contextual
      information. Mobile phones were used as the primary mode of EMA data collection
      in 48% (20/42) of the reviewed studies. In total, 12% (5/42) of the studies used
      wearable devices in addition to the EMA data collection platforms. About half of
      the studies (62%, 24/42) recruited youth from nonclinical settings. Most (98%,
      41/42) studies used a time-based sampling protocol. Among these studies, most
      (95%, 39/41) prompted youth 2-9 times daily, for a study length ranging from 2-42
      days. Sampling frequency and study length did not differ between studies with
      participants from clinical versus nonclinical settings. Most (88%, 36/41) studies
      with a time-based sampling protocol defined compliance as the proportion of
      prompts to which participants responded. In these studies, the weighted average
      compliance rate was 78.3%. The average compliance rates were not different
      between studies with clinical (76.9%) and nonclinical (79.2%; P=.29) and studies
      that used only a mobile-EMA platform (77.4%) and mobile platform plus additional
      wearable devices (73.0%, P=.36). Among clinical studies, the mean compliance rate
      was significantly lower in studies that prompted participants 2-3 times (73.5%)
      or 4-5 times (66.9%) compared with studies with a higher sampling frequency (6+
      times: 89.3%). Among nonclinical studies, a higher average compliance rate was
      observed in studies that prompted participants 2-3 times daily (91.7%) compared
      with those that prompted participants more frequently (4-5 times: 77.4%; 6+
      times: 75.0%). The reported compliance rates did not differ by duration of EMA
      period among studies from either clinical or nonclinical settings. CONCLUSIONS:
      The compliance rate among mobile-EMA studies in youth is moderate but suboptimal.
      Study design may affect protocol compliance differently between clinical and
      nonclinical participants; including additional wearable devices did not affect
      participant compliance. A more consistent compliance-related result reporting
      practices can facilitate understanding and improvement of participant compliance
      with EMA data collection among youth.

PMID- 28446419
TI  - The Smartphone Peer Physical Activity Counseling (SPPAC) Program for Manual
      Wheelchair Users: Protocol of a Pilot Randomized Controlled Trial.
AB  - BACKGROUND: Physical activity (PA) must be performed regularly to accrue health
      benefits. However, the majority of manual wheelchair users do not meet PA
      recommendations. Existing community-based PA programs for manual wheelchair users
      appear to work, but effect sizes are small and retention is low. Existing PA
      programs may not fully implement some psychosocial factors that are strongly
      linked with PA (eg, autonomy). The use of peers and mobile phone technology in
      the Smartphone Peer PA Counseling (SPPAC) program represents a novel approach to
      cultivating a PA-supportive environment for manual wheelchair users. OBJECTIVE:
      The primary objective is to compare change in objective PA between the
      experimental (SPPAC) and control groups from baseline to postintervention (10
      weeks) and follow-up (3 months). Changes in and relationships between subjective
      PA, wheelchair skills, motivation, self-efficacy (for overcoming barriers to PA
      for manual wheelchair use), satisfaction of psychological needs for PA, and
      satisfaction with PA participation will be explored (secondary outcome). Program
      implementation will be explored (tertiary objective). METHODS: A total of 38
      community-living manual wheelchair users (>=18 years) will be recruited in a
      randomized controlled trial (RCT). Participants in both the control and
      experimental groups will receive existing PA guidelines. Participants in the
      experimental group will also receive the SPPAC program: 14 sessions (~30 min)
      over a 10-week period delivered by a peer trainer using a mobile phone. PA
      activities will be based on individuals' preferences and goals. Implementation of
      important theoretical variables will be enforced through a peer-trainer
      checklist. Outcomes for objective PA (primary) and subjective PA, wheelchair
      skills, motivation, self-efficacy, satisfaction of psychological needs, and
      satisfaction with participation will be collected at three time points (baseline,
      postintervention, follow-up). Multiple imputations will be used to treat missing
      data. A mixed-model ANCOVA will be conducted, controlling for covariates (primary
      and secondary objectives). The strength and direction of the relationships
      between the primary and secondary outcomes will be explored (secondary
      objective). Descriptive and content analysis will be used to appraise program
      implementation (tertiary objective). RESULTS: Funding has been obtained from the
      Craig Neilsen Foundation and the Canadian Disability Participation Project, with
      additional funds being sought from the Canadian Institute for Health Research and
      Fonds de Recherche du Quebec-Sante. Pilot evaluation of intervention
      implementation is currently underway, with enrollment anticipated to begin early
      2018. CONCLUSIONS: There may be substantial benefits for the SPPAC program
      including limited burden on health care professionals, decreased barriers (eg.
      accessibility, transportation), development of peer social supports, and
      potential cost savings related to physical inactivity. Before conducting a large
      and expensive multisite RCT within a small heterogeneous population of manual
      wheelchair users, a pilot study affords a prudent step to establishing an
      adequate study protocol and implementation strategies. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02826707; https://clinicaltrials.gov/ct2/show/NCT02826707
      (Archived by WebCite at http://www.webcitation.org/6pqIc14dU).

PMID- 28446420
TI  - Measuring Sexual Behavior Stigma to Inform Effective HIV Prevention and Treatment
      Programs for Key Populations.
AB  - BACKGROUND: The levels of coverage of human immunodeficiency virus (HIV)
      treatment and prevention services needed to change the trajectory of the HIV
      epidemic among key populations, including gay men and other men who have sex with
      men (MSM) and sex workers, have consistently been shown to be limited by stigma.
      OBJECTIVE: The aim of this study was to propose an agenda for the goals and
      approaches of a sexual behavior stigma surveillance effort for key populations,
      with a focus on collecting surveillance data from 4 groups: (1) members of key
      population groups themselves (regardless of HIV status), (2) people living with
      HIV (PLHIV) who are also members of key populations, (3) members of nonkey
      populations, and (4) health workers. METHODS: We discuss strengths and weaknesses
      of measuring multiple different types of stigma including perceived, anticipated,
      experienced, perpetrated, internalized, and intersecting stigma as measured among
      key populations themselves, as well as attitudes or beliefs about key populations
      as measured among other groups. RESULTS: With the increasing recognition of the
      importance of stigma, consistent and validated stigma metrics for key populations
      are needed to monitor trends and guide immediate action. Evidence-based stigma
      interventions may ultimately be the key to overcoming the barriers to coverage
      and retention in life-saving antiretroviral-based HIV prevention and treatment
      programs for key populations. CONCLUSIONS: Moving forward necessitates the
      integration of validated stigma scales in routine HIV surveillance efforts, as
      well as HIV epidemiologic and intervention studies focused on key populations, as
      a means of tracking progress toward a more efficient and impactful HIV response.

PMID- 28446422
TI  - Web-Based Medical Appointment Systems: A Systematic Review.
AB  - BACKGROUND: Health care is changing with a new emphasis on patient-centeredness.
      Fundamental to this transformation is the increasing recognition of patients'
      role in health care delivery and design. Medical appointment scheduling, as the
      starting point of most non-urgent health care services, is undergoing major
      developments to support active involvement of patients. By using the Internet as
      a medium, patients are given more freedom in decision making about their
      preferences for the appointments and have improved access. OBJECTIVE: The purpose
      of this study was to identify the benefits and barriers to implement Web-based
      medical scheduling discussed in the literature as well as the unmet needs under
      the current health care environment. METHODS: In February 2017, MEDLINE was
      searched through PubMed to identify articles relating to the impacts of Web-based
      appointment scheduling. RESULTS: A total of 36 articles discussing 21 Web-based
      appointment systems were selected for this review. Most of the practices have
      positive changes in some metrics after adopting Web-based scheduling, such as
      reduced no-show rate, decreased staff labor, decreased waiting time, and improved
      satisfaction, and so on. Cost, flexibility, safety, and integrity are major
      reasons discouraging providers from switching to Web-based scheduling. Patients'
      reluctance to adopt Web-based appointment scheduling is mainly influenced by
      their past experiences using computers and the Internet as well as their
      communication preferences. CONCLUSIONS: Overall, the literature suggests a
      growing trend for the adoption of Web-based appointment systems. The findings of
      this review suggest that there are benefits to a variety of patient outcomes from
      Web-based scheduling interventions with the need for further studies.

PMID- 28446423
TI  - Evaluation of a Mindfulness-Based Mobile App Aimed at Promoting Awareness of
      Weight-Related Behaviors in Adolescents: A Pilot Study.
AB  - BACKGROUND: Mindfulness-based interventions are reported to be highly acceptable
      and have positive effects on youth, yet most are clinic- or school-based aimed at
      emotional regulation or academic performance. To provide flexible program
      delivery, we developed and tested a standalone mindfulness-based app aimed at
      improving weight-related behaviors (eg, diet, physical activity, sleep) in
      adolescents. OBJECTIVE: Our objective was to assess the feasibility,
      acceptability, and utility of a mindfulness-based mobile app. METHODS: In a
      single-arm pilot study, 15 adolescents (14-18 years) were prompted to access the
      app once a day, every day for 6 weeks. Outcomes were measured by in-app and
      poststudy surveys, and descriptive statistical analyses were performed. Time
      within a mindfulness state was self-reported during weekly timed practices.
      RESULTS: The app was rated highly for content and encouraging the practice of
      activities to promote mindfulness states. Teens reported increased awareness of
      eating behaviors and high adherence, particularly during physically active
      practices. Average self-reported time spent in a mindfulness state increased 2.5
      times by week 6 (78 [SD 17] seconds) compared to week 1 (31 [SD 21] seconds).
      CONCLUSIONS: The high acceptability and utility ratings of the app, increases in
      reported time in mindfulness states, and high frequency of participation,
      including mindful eating and physical activity, suggest the mindfulness-based
      mobile app has the potential to improve awareness of weight-related behaviors.

PMID- 28446421
TI  - Testing a Computerized Cognitive Training Protocol in Adults Aging With HIV
      Associated Neurocognitive Disorders: Randomized Controlled Trial Rationale and
      Protocol.
AB  - BACKGROUND: HIV-associated neurocognitive disorders occur in nearly 50% of adults
      with HIV. Such disorders can interfere with everyday functioning such as driving
      and medication adherence. Therefore, cognitive interventions are needed to
      address such neurocognitive disorders as well as improve everyday functioning,
      especially as people age with HIV. OBJECTIVE: This article reports and discusses
      the overall rationale and development of speed of processing training, a
      computerized Internet cognitive training program, to improve this specific
      neurocognitive ability as well as everyday functioning and quality of life in
      adults aging with HIV. Although this protocol has been shown to improve speed of
      processing, everyday functioning, and quality of life in healthy, community
      dwelling older adults in the advanced cognitive training in vital elderly
      (ACTIVE) study, its efficacy in adults aging with HIV has not been established.
      Nevertheless, such a cognitive intervention is particularly germane as 52%-59% of
      adults with HIV experience HIV-associated neurocognitive disorders (HAND), and
      both the frequency and severity of such disorders may increase with advancing
      age. METHODS: The description of this longitudinal randomized controlled trial
      covers the following: (1) rationale for speed of processing training in this
      clinical population, (2) overview of overall study design, (3) eligibility
      criteria and HAND, (4) intervention dosage, (5) assessment battery, and (6)
      examination of biomarkers. RESULTS: The project was funded in April 2016 and
      enrolment is on-going. The first results are expected to be submitted for
      publication in 2020. CONCLUSIONS: Similar novel cognitive intervention approaches
      are suggested as they may be of value to those with HAND and may utilize similar
      features of this current randomized controlled trial (RCT) protocol to examine
      their therapeutic efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02758093;
      https://clinicaltrials.gov/ct2/show/NCT02758093 (Archived by Webcite at
      http://www.webcitation.org/6p8C5fBCX).

PMID- 28446424
TI  - Hormone supplementation for pubertal induction in girls.
AB  - Pubertal induction in girls with ovarian insufficiency aims to mimic normal
      puberty, a highly complex process. Here we amalgamate the sparse global evidence
      and propose three options for pubertal induction regimens including oral
      ethinyloestradiol, and oral and transdermal 17beta-oestradiol. The introduction
      of progestogens is discussed and the transition to hormone supplementation for
      adult women. The merits and disadvantages of the different options are detailed.
      The available evidence indicates that transdermal 17beta-oestradiol has the most
      favourable efficacy, safety and cost profile but randomised controlled trials are
      urgently required to determine which regimen provides the best clinical outcomes.

PMID- 28446425
TI  - Prevalence and risk factors for functional constipation in adolescent Nigerians.
AB  - OBJECTIVES: To determine the prevalence and risk factors for functional
      constipation (FC) in adolescent Nigerians. METHOD: A cross-sectional study was
      conducted in rural and urban areas of two states in the southern part of Nigeria.
      Adolescents aged 10-18 years were recruited from 11 secondary schools, using a
      stratified random sampling technique. A validated self-administered questionnaire
      on Rome III criteria for diagnosing FC and its predisposing factors was filled by
      each participant in a classroom setting. RESULTS: A total of 874 questionnaires
      was distributed and 818 (93%) properly filled questionnaires were included in the
      analysis. The mean age of the participants was 14.6+/-2.0 years with 409 (50%)
      being boys. FC was present in 223 (27%) with no difference in prevalence between
      sexes. Prevalence of FC was 29% in urban areas and 26% in rural areas (p>0.05).
      The condition was significantly associated with low social class (p=0.013).
      Exposure to stressful life events at home and school did not predispose the
      participants to develop FC. CONCLUSIONS: FC is a significant health problem among
      adolescent Nigerians. The condition is associated with low social class.

PMID- 28446426
TI  - Ablation of S1P3 receptor protects mouse soleus from age-related drop in muscle
      mass, force, and regenerative capacity.
AB  - We investigated the effects of S1P3 deficiency on the age-related atrophy,
      decline in force, and regenerative capacity of soleus muscle from 23-mo-old male
      (old) mice. Compared with muscle from 5-mo-old (adult) mice, soleus mass and
      muscle fiber cross-sectional area (CSA) in old wild-type mice were reduced by
      ~26% and 24%, respectively. By contrast, the mass and fiber CSA of soleus muscle
      in old S1P3-null mice were comparable to those of adult muscle. Moreover, in
      soleus muscle of wild-type mice, twitch and tetanic tensions diminished from
      adulthood to old age. A slowing of contractile properties was also observed in
      soleus from old wild-type mice. In S1P3-null mice, neither force nor the
      contractile properties of soleus changed during aging. We also evaluated the
      regenerative capacity of soleus in old S1P3-null mice by stimulating muscle
      regeneration through myotoxic injury. After 10 days of regeneration, the mean
      fiber CSA of soleus in old wild-type mice was significantly smaller (-28%)
      compared with that of regenerated muscle in adult mice. On the contrary, the mean
      fiber CSA of regenerated soleus in old S1P3-null mice was similar to that of
      muscle in adult mice. We conclude that in the absence of S1P3, soleus muscle is
      protected from the decrease in muscle mass and force, and the attenuation of
      regenerative capacity, all of which are typical characteristics of aging.

PMID- 28446427
TI  - Airway epithelial anion secretion and barrier function following exposure to
      fungal aeroallergens: role of oxidative stress.
AB  - Aeroallergens produced by Alternaria alternata can elicit life-threatening
      exacerbations of asthma in patients sensitized to this fungus. In this study, the
      effect of Alternaria on ion transport mechanisms underlying mucociliary clearance
      and airway epithelial barrier function was investigated in human airway
      epithelial cells. Apical exposure to Alternaria induced an increase in anion
      secretion that was inhibited by blockers of CFTR and Ca2+-activated Cl- channels.
      Stimulation of anion secretion was dependent on Ca2+ uptake from the apical
      solution. Alternaria exposure also produced an increase in reactive oxygen
      species (ROS) that was blocked by pretreatment with the oxidant scavenger
      glutathione (GSH). GSH and the NADPH oxidase inhibitor/complex 1 electron
      transport inhibitor diphenylene iodonium chloride (DPI) blocked ATP release and
      the increase in intracellular [Ca2+] evoked by AlternariaAlternaria also
      decreased transepithelial resistance, and a portion of this effect was dependent
      on the increase in ROS. However, the Alternaria-induced increase in
      unidirectional dextran (molecular mass = 4,000 Da) flux across the epithelium
      could not be accounted for by increased oxidative stress. These results support
      the conclusion that oxidative stress induced by Alternaria was responsible for
      regulating Ca2+-dependent anion secretion and tight junction electrical
      resistance that would be expected to affect mucociliary clearance.

PMID- 28446430
TI  - India launches strategy to curb antimicrobial resistance.

PMID- 28446432
TI  - Five minutes with . . . Jane Sandall.

PMID- 28446428
TI  - Mortality risk during and after opioid substitution treatment: systematic review
      and meta-analysis of cohort studies.
AB  - Objective To compare the risk for all cause and overdose mortality in people with
      opioid dependence during and after substitution treatment with methadone or
      buprenorphine and to characterise trends in risk of mortality after initiation
      and cessation of treatment.Design Systematic review and meta-analysis.Data
      sources Medline, Embase, PsycINFO, and LILACS to September 2016.Study selection
      Prospective or retrospective cohort studies in people with opioid dependence that
      reported deaths from all causes or overdose during follow-up periods in and out
      of opioid substitution treatment with methadone or buprenorphine.Data extraction
      and synthesis Two independent reviewers performed data extraction and assessed
      study quality. Mortality rates in and out of treatment were jointly combined
      across methadone or buprenorphine cohorts by using multivariate random effects
      meta-analysis.Results There were 19 eligible cohorts, following 122 885 people
      treated with methadone over 1.3-13.9 years and 15 831 people treated with
      buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and
      36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to
      in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and
      9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend
      analysis, all cause mortality dropped sharply over the first four weeks of
      methadone treatment and decreased gradually two weeks after leaving treatment.
      All cause mortality remained stable during induction and remaining time on
      buprenorphine treatment. Overdose mortality evolved similarly, with pooled
      overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of
      methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4
      and 4.6 in and out of buprenorphine treatment.Conclusions Retention in methadone
      and buprenorphine treatment is associated with substantial reductions in the risk
      for all cause and overdose mortality in people dependent on opioids. The
      induction phase onto methadone treatment and the time immediately after leaving
      treatment with both drugs are periods of particularly increased mortality risk,
      which should be dealt with by both public health and clinical strategies to
      mitigate such risk. These findings are potentially important, but further
      research must be conducted to properly account for potential confounding and
      selection bias in comparisons of mortality risk between opioid substitution
      treatments, as well as throughout periods in and out of each treatment.

PMID- 28446433
TI  - In CLL, comorbidities and the complex karyotype are associated with an inferior
      outcome independently of CLL-IPI.

PMID- 28446435
TI  - Addiction to exercise.

PMID- 28446436
TI  - Is there any place for counterterrorism in the NHS?

PMID- 28446434
TI  - Donor-engrafted CHIP is common among stem cell transplant recipients with
      unexplained cytopenias.

PMID- 28446437
TI  - NHS must "get its act together" to secure cash for new buildings.

PMID- 28446438
TI  - Opioid substitution treatment is linked to reduced risk of death in opioid use
      disorder.

PMID- 28446440
TI  - Nod for Atezolizumab in Advanced Bladder Cancer.
AB  - The FDA approved atezolizumab to treat advanced bladder cancer when cisplatin
      chemotherapy is contraindicated. The approval offers a potentially more effective
      alternative to carboplatin-based chemotherapy for frail, elderly patients.

PMID- 28446439
TI  - PAX3-FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain
      Vulnerability.
AB  - Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and
      adolescent young adults, driven primarily by the chimeric transcription factor
      PAX3-FOXO1. The mechanisms by which PAX3-FOXO1 dysregulates chromatin are
      unknown. We find PAX3-FOXO1 reprograms the cis-regulatory landscape by inducing
      de novo super enhancers. PAX3-FOXO1 uses super enhancers to set up autoregulatory
      loops in collaboration with the master transcription factors MYOG, MYOD, and
      MYCN. This myogenic super enhancer circuitry is consistent across cell lines and
      primary tumors. Cells harboring the fusion gene are selectively sensitive to
      small-molecule inhibition of protein targets induced by, or bound to, PAX3-FOXO1
      occupied super enhancers. Furthermore, PAX3-FOXO1 recruits and requires the BET
      bromodomain protein BRD4 to function at super enhancers, resulting in a complete
      dependence on BRD4 and a significant susceptibility to BRD inhibition. These
      results yield insights into the epigenetic functions of PAX3-FOXO1 and reveal a
      specific vulnerability that can be exploited for precision therapy.Significance:
      PAX3-FOXO1 drives pediatric fusion-positive rhabdomyosarcoma, and its chromatin
      level functions are critical to understanding its oncogenic activity. We find
      that PAX3-FOXO1 establishes a myoblastic super enhancer landscape and creates a
      profound subtype-unique dependence on BET bromodomains, the inhibition of which
      ablates PAX3-FOXO1 function, providing a mechanistic rationale for exploring BET
      inhibitors for patients bearing PAX-fusion rhabdomyosarcoma. Cancer Discov; 7(8);
      884-99. (c)2017 AACR.This article is highlighted in the In This Issue feature, p.
      783.

PMID- 28446442
TI  - Paracentral acute middle maculopathy: precursor to macular thinning in sickle
      cell retinopathy.
AB  - We present a case of paracentral acute middle maculopathy (PAMM) in a patient
      with sickle cell disease (SCD). Though gradual capillary loss may contribute to
      pathophysiology of sickle cell retinopathy as well, our case suggests that PAMM
      may be the precursor lesion to macular thinning commonly observed in patients
      with SCD. In addition, fluorescein angiography may be unable to detect these
      acute vascular events occurring at the deep capillary plexus.

PMID- 28446443
TI  - Enteritis with pneumatosis intestinalis following rotavirus immunisation in an
      infant with short bowel syndrome.
AB  - Rotavirus vaccines now form part of the national immunisation schedule in many
      countries. Contraindications to its use are few but do not currently include
      infants with short bowel syndrome (SBS). We present a nearly 3-month-old boy with
      SBS who developed enteritis with pneumatosis intestinalis following
      administration of the Rotarix vaccine.

PMID- 28446441
TI  - Long-Term Persistence of Cell-Mediated and Humoral Responses to A(H1N1)pdm09
      Influenza Virus Vaccines and the Role of the AS03 Adjuvant System in Adults
      during Two Randomized Controlled Trials.
AB  - We investigated the role of AS03A (here AS03), an alpha-tocopherol oil-in-water
      emulsion-based adjuvant system, on the long-term persistence of humoral and cell
      mediated immune responses to A(H1N1)pdm09 influenza vaccines. In two studies, a
      total of 261 healthy adults (<=60 years old) were randomized to receive two doses
      of AS03-adjuvanted vaccine containing 3.75 MUg of hemagglutinin (HA) or
      nonadjuvanted vaccine containing 15 MUg of hemagglutinin (in study A) or 3.75 MUg
      of hemagglutinin (in study B) 21 days apart. Hemagglutination inhibition (HI)
      antibody, memory B-cell, and CD4+/CD8+ T-cell responses were characterized up to
      1 year following dose 1. We also assessed the effects of age and seasonal
      influenza vaccination history. AS03-adjuvanted (3.75 MUg HA) vaccine and
      nonadjuvanted vaccine at 15 MUg but not at 3.75 MUg HA elicited HI antibody
      responses persisting at levels that continued to meet European licensure criteria
      through month 12. At month 12, the geometric mean titer for AS03-adjuvanted
      vaccine was similar to that for nonadjuvanted (15-MUg) vaccine in study A (1:86
      and 1:88, respectively) and higher than that for nonadjuvanted (3.75-MUg) vaccine
      in study B (1:77 and 1:35, respectively). A(H1N1)pdm09-specific CD4+ T-cell and B
      cell responses were stronger in AS03-adjuvanted groups and persisted only in
      these groups for 12 months at levels exceeding prevaccination frequencies.
      Advancing age and a seasonal vaccination history tended to reduce HI antibody and
      memory B-cell responses and, albeit less consistently, CD4+ T-cell responses.
      Thus, AS03 seemed to enhance the persistence of humoral and cell-mediated
      responses to A(H1N1)pdm09 vaccine, allowing for antigen sparing and mitigating
      potential negative effects of age and previous seasonal vaccination. (These
      studies have been registered at ClinicalTrials.gov under registration no.
      NCT00968539 and NCT00989287.).

PMID- 28446444
TI  - Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single
      Human Heart Biopsy.
AB  - RATIONALE: The relative actions and synergism between distinct myocardial-derived
      stem cell populations remain obscure. Ongoing debates on optimal cell
      population(s) for treatment of heart failure prompted implementation of a
      protocol for isolation of multiple stem cell populations from a single myocardial
      tissue sample to develop new insights for achieving myocardial regeneration.
      OBJECTIVE: Establish a robust cardiac stem cell isolation and culture protocol to
      consistently generate 3 distinct stem cell populations from a single human heart
      biopsy. METHODS AND RESULTS: Isolation of 3 endogenous cardiac stem cell
      populations was performed from human heart samples routinely discarded during
      implantation of a left ventricular assist device. Tissue explants were
      mechanically minced into 1 mm3 pieces to minimize time exposure to collagenase
      digestion and preserve cell viability. Centrifugation removes large
      cardiomyocytes and tissue debris producing a single cell suspension that is
      sorted using magnetic-activated cell sorting technology. Initial sorting is based
      on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit+ cell
      populations yielding a mixture of cardiac progenitor cells and endothelial
      progenitor cells. Flowthrough c-Kit- mesenchymal stem cells are positively
      selected by surface expression of markers CD90 and CD105. After 1 week of
      culture, the c-Kit+ population is further enriched by selection for a CD133+
      endothelial progenitor cell population. Persistence of respective cell surface
      markers in vitro is confirmed both by flow cytometry and immunocytochemistry.
      CONCLUSIONS: Three distinct cardiac cell populations with individualized
      phenotypic properties consistent with cardiac progenitor cells, endothelial
      progenitor cells, and mesenchymal stem cells can be successfully concurrently
      isolated and expanded from a single tissue sample derived from human heart
      failure patients.

PMID- 28446446
TI  - The Cardiovascular Health in Ambulatory Care Research Team performance indicators
      for the primary prevention of cardiovascular disease: a modified Delphi panel
      study.
AB  - BACKGROUND: High-quality ambulatory care can reduce cardiovascular disease risk,
      but important gaps exist in the provision of cardiovascular preventive care. We
      sought to develop a set of key performance indicators that can be used to measure
      and improve cardiovascular care in the primary care setting. METHODS: As part of
      the Cardiovascular Health in Ambulatory Care Research Team initiative, we
      established a 14-member multidisciplinary expert panel to develop a set of
      indicators for measuring primary prevention performance in ambulatory
      cardiovascular care. We used a 2-stage modified Delphi panel process to rate
      potential indicators, which were identified from the literature and national
      cardiovascular organizations. The top-rated indicators were pilot tested to
      determine their measurement feasibility with the use of data routinely collected
      in the Canadian health care system. RESULTS: A set of 28 indicators of primary
      prevention performance were identified, which were grouped into 5 domains: risk
      factor prevalence, screening, management, intermediate outcomes and long-term
      outcomes. The indicators reflect the major cardiovascular risk factors including
      smoking, obesity, hypertension, diabetes, dyslipidemia and atrial fibrillation.
      All indicators were determined to be amenable to measurement with the use of
      population-based administrative (physician claims, hospital admission,
      laboratory, medication), survey or electronic medical record databases.
      INTERPRETATION: The Cardiovascular Health in Ambulatory Care Research Team
      indicators of primary prevention performance provide a framework for the
      measurement of cardiovascular primary prevention efforts in Canada. The
      indicators may be used by clinicians, researchers and policy-makers interested in
      measuring and improving the prevention of cardiovascular disease in ambulatory
      care settings.

PMID- 28446447
TI  - Concussion recognition tool 5(c).

PMID- 28446448
TI  - Sport concussion assessment tool for childrens ages 5 to 12 years.

PMID- 28446445
TI  - Susceptibility Testing of Medically Important Parasites.
AB  - In the last 2 decades, renewed attention to neglected tropical diseases (NTDs)
      has spurred the development of antiparasitic agents, especially in light of
      emerging drug resistance. The need for new drugs has required in vitro screening
      methods using parasite culture. Furthermore, clinical laboratories sought to
      correlate in vitro susceptibility methods with treatment outcomes, most notably
      with malaria. Parasites with their various life cycles present greater complexity
      than bacteria, for which standardized susceptibility methods exist. This review
      catalogs the state-of-the-art methodologies used to evaluate the effects of drugs
      on key human parasites from the point of view of drug discovery as well as the
      need for laboratory methods that correlate with clinical outcomes.

PMID- 28446449
TI  - The Berlin 2016 process: a summary of methodology for the 5th International
      Consensus Conference on Concussion in Sport.
AB  - The purpose of this paper is to summarise the methodology for the 5th
      International Consensus Conference on Concussion in Sport. The 18 months of
      preparation included engagement of a scientific committee, an expert panel of 33
      individuals in the field of concussion and a modified Delphi technique to
      determine the primary questions to be answered. The methodology also involved the
      writing of 12 systematic reviews to inform the consensus conference and
      submission and review of scientific abstracts. The meeting itself followed a 2
      day open format, a 1-day closed expert panel meeting and two additional half day
      meetings to develop the Concussion Recognition Tool 5 (Pocket CRT5), Sport
      Concussion Assessment Tool 5 (SCAT5) and Child SCAT5.

PMID- 28446451
TI  - Sport concussion assessment tool - 5th edition.

PMID- 28446450
TI  - The Concussion Recognition Tool 5th Edition (CRT5): Background and rationale.
AB  - The Concussion Recognition Tool 5 (CRT5) is the most recent revision of the
      Pocket Sport Concussion Assessment Tool 2 that was initially introduced by the
      Concussion in Sport Group in 2005. The CRT5 is designed to assist non-medically
      trained individuals to recognise the signs and symptoms of possible sport-related
      concussion and provides guidance for removing an athlete from play/sport and to
      seek medical attention. This paper presents the development of the CRT5 and
      highlights the differences between the CRT5 and prior versions of the instrument.

PMID- 28446452
TI  - The Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5): Background
      and rationale.
AB  - This article presents the Child Sport Concussion Assessment Tool 5th Edition
      (Child SCAT5). The Sport Concussion Assessment Tool was introduced in 2004,
      following the 2nd International Conference on Concussion in Sport in Prague,
      Czech Republic. Following the 4th International Consensus Conference, held in
      Zurich, Switzerland, in 2012, the SCAT 3rd edition (Child SCAT3) was developed
      for children aged between 5 and12 years. Research to date was reviewed and
      synthesised for the 5th International Consensus Conference on Concussion in Sport
      in Berlin, Germany, leading to the current revision of the test, the Child SCAT5.
      This article describes the development of the Child SCAT5.

PMID- 28446454
TI  - Epidemiology of injuries in judo: a cross-sectional survey of severe injuries
      based on time loss and reduction in sporting level.
AB  - BACKGROUND: Sport injury severity can be detected by duration of time loss and
      reduction of sporting performance. AIM: To detect injury type-specific time loss
      duration and sporting performance reduction in judo. METHODS: An online survey of
      active and former judo athletes was conducted (exclusion criterion: incomplete
      questionnaire). Only injuries causing more than 3 weeks' time loss were recorded.
      Athletes classified themselves into performance classes. Injury type-specific
      frequencies were recorded according to gender, age and performance level. Injury
      severity was assessed by time loss duration and performance reduction. RESULTS:
      The study included 4659 athletes (65% male, 38% competitive sports). The most
      commonly injured body regions were the upper extremity (41%) and the lower
      extremity (39%). Anterior cruciate ligament (ACL) ruptures were the most severe
      injury type (time loss: 4% of cases 3-6 weeks, 6% 6-12 weeks, 26% 3-6 months, 32%
      6-9 months, 18% 9-12 months, 14%>12 months; performance reduction: 32% same
      level, 39% slightly reduced, 24% strongly reduced, 5% stopped judo). The second
      most severe type of injury was a vertebral disc prolapse (time loss: 26% 3-6
      weeks, 31% 6-12 weeks, 20% 3-6 months, 7% 6-9 months, 3% 9-12 months 13%>12
      months; reduction of sporting performance: 39% same level, 34% slightly reduced,
      20% strongly reduced, 8% stopped judo). CONCLUSION: Across genders and
      performance levels, ACL ruptures and vertebral disc prolapses were the most
      severe injuries with respect to time loss and sporting performance reduction.

PMID- 28446453
TI  - The Sport Concussion Assessment Tool 5th Edition (SCAT5): Background and
      rationale.
AB  - This paper presents the Sport Concussion Assessment Tool 5th Edition (SCAT5),
      which is the most recent revision of a sport concussion evaluation tool for use
      by healthcare professionals in the acute evaluation of suspected concussion. The
      revision of the SCAT3 (first published in 2013) culminated in the SCAT5. The
      revision was based on a systematic review and synthesis of current research,
      public input and expert panel review as part of the 5th International Consensus
      Conference on Concussion in Sport held in Berlin in 2016. The SCAT5 is intended
      for use in those who are 13 years of age or older. The Child SCAT5 is a tool for
      those aged 5-12 years, which is discussed elsewhere.

PMID- 28446455
TI  - The economic burden of physical inactivity: a systematic review and critical
      appraisal.
AB  - OBJECTIVE: To summarise the literature on the economic burden of physical
      inactivity in populations, with emphases on appraising the methodologies and
      providing recommendations for future studies. DESIGN: Systematic review following
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines
      (PROSPERO registration number CRD42016047705). DATA SOURCES: Electronic databases
      for peer-reviewed and grey literature were systematically searched, followed by
      reference searching and consultation with experts. ELIGIBILITY CRITERIA: Studies
      that examined the economic consequences of physical inactivity in a
      population/population-based sample, with clearly stated methodologies and at
      least an abstract/summary written in English. RESULTS: Of the 40 eligible
      studies, 27 focused on direct healthcare costs only, 13 also estimated indirect
      costs and one study additionally estimated household costs. For direct costs, 23
      studies used a population attributable fraction (PAF) approach with estimated
      healthcare costs attributable to physical inactivity ranging from 0.3% to 4.6% of
      national healthcare expenditure; 17 studies used an econometric approach, which
      tended to yield higher estimates than those using a PAF approach. For indirect
      costs, 10 studies used a human capital approach, two used a friction cost
      approach and one used a value of a statistical life approach. Overall, estimates
      varied substantially, even within the same country, depending on analytical
      approaches, time frame and other methodological considerations. CONCLUSION:
      Estimating the economic burden of physical inactivity is an area of increasing
      importance that requires further development. There is a marked lack of
      consistency in methodological approaches and transparency of reporting. Future
      studies could benefit from cross-disciplinary collaborations involving economists
      and physical activity experts, taking a societal perspective and following best
      practices in conducting and reporting analysis, including accounting for
      potential confounding, reverse causality and comorbidity, applying discounting
      and sensitivity analysis, and reporting assumptions, limitations and
      justifications for approaches taken. We have adapted the Consolidated Health
      Economic Evaluation Reporting Standards checklist as a guide for future estimates
      of the economic burden of physical inactivity and other risk factors.

PMID- 28446456
TI  - Injuries impair the chance of successful performance by sportspeople: a
      systematic review.
AB  - BACKGROUND: Cost-benefit analyses have been proposed for determining acceptable
      risk of injury regarding training and competition participation. Currently, there
      is no best evidence synthesis of the literature evaluating the relationship
      between injury/illness and chance of success or failure. OBJECTIVE: To evaluate
      the relationship between injury and/or illness and success and/or failure in
      athletic populations (individual and team sports). METHODS: This review was
      prospectively registered (PROSPERO CRD42016036729) and a systematic electronic
      search was conducted in May 2016. Inclusion criterion was any study design
      describing the association between injury and/or illness and success or failure
      in athletic performance. Two independent authors screened search results,
      performed data extraction and assessed methodological quality and strength of
      evidence using a modified Downs and Black appraisal tool and a modified van
      Tulder method, respectively. RESULTS: Of 10 546 titles identified, 14 satisfied
      the inclusion criteria and 7 had low risk of bias. Outcome measures associated
      with success and/or failure included: (1) availability of team members, (2)
      injury incidence, (3) injury burden, (4) squad utilisation and (5, 6)
      precompetition and in-competition injury. There was strong evidence that (1)
      increased availability of team members/athletes decreased the risk of failure and
      (2) precompetition and in-competition injuries were associated with increased
      risk of failure. CONCLUSIONS: Injuries have a detrimental impact on team and
      individual athletic success. Increased player availability improves chances of
      success. Conversely, injuries sustained both prior to and during competition may
      increase risk of failure. Injury prevention should therefore be a priority for
      maximising athletic performance.

PMID- 28446458
TI  - Caspase-11 promotes cisplatin-induced renal tubular apoptosis through a caspase-3
      dependent pathway.
AB  - Renal tubular injury is the hallmark of cisplatin-induced nephrotoxicity. Caspase
      11, a member of the caspase family, plays an important role in inflammation and
      cell death. However, its role in cisplatin-induced renal tubular injury remains
      unclear. In cisplatin-treated mice, caspase-11 expression was significantly
      elevated and the expression of caspase-11 was mainly located in renal tubule.
      Inhibition of caspase-11 by small-interference RNA or its inhibitor wedelolactone
      attenuated cisplatin-induced renal dysfunction and tubular injury. In cultured
      primary renal tubular epithelial cells, cisplatin significantly promoted the
      expression and activation of caspase-11. Inhibition of caspase-11 by small
      interference RNA reduced cisplatin-induced cell apoptosis. Overexpression of
      caspase-11 promoted cell apoptosis by activating the caspase-3-related cell
      apoptosis. Furthermore, coimmunoprecipitation results showed there was a direct
      interaction between caspase-11 and caspase-3, and the interaction was enhanced by
      cisplatin. The fluorescence confocal microscopy results showed that caspase-11
      and caspase-3 were colocalized in the cytoplasm of renal tubular epithelial
      cells. These results demonstrate that caspase-11 plays an important role in
      cisplatin-induced renal tubular injury. Caspase-11 promotes renal epithelial cell
      apoptosis by activating the caspase-3-dependent apoptotic pathway. Caspase-11
      might be a potential target for therapeutic treatment against cisplatin-induced
      nephrotoxicity.

PMID- 28446457
TI  - Consensus statement on concussion in sport-the 5th international conference on
      concussion in sport held in Berlin, October 2016.

PMID- 28446459
TI  - Distinct roles of arginases 1 and 2 in diabetic nephropathy.
AB  - Diabetes is the leading cause of end-stage renal disease, resulting in a
      significant health care burden and loss of economic productivity by affected
      individuals. Because current therapies for progression of diabetic nephropathy
      (DN) are only moderately successful, identification of underlying mechanisms of
      disease is essential to develop more effective therapies. We showed previously
      that inhibition of arginase using S-(2-boronoethyl)-l-cysteine (BEC) or genetic
      deficiency of the arginase-2 isozyme was protective against key features of
      nephropathy in diabetic mouse models. However, those studies did not determine
      whether all markers of DN were dependent only on arginase-2 expression. The
      objective of this study was to identify features of DN that are associated
      specifically with expression of arginase-1 or -2. Elevated urinary albumin
      excretion rate and plasma urea levels, increases in renal fibronectin mRNA
      levels, and decreased renal medullary blood flow were associated almost
      completely and specifically with arginase-2 expression, indicating that arginase
      2 selectively mediates major aspects of diabetic renal injury. However, increases
      in renal macrophage infiltration and renal TNF-alpha mRNA levels occurred
      independent of arginase-2 expression but were almost entirely abolished by
      treatment with BEC, indicating a distinct role for arginase-1. We therefore
      generated mice with a macrophage-specific deletion of arginase-1 (CD11bCre
      /Arg1fl/fl ). CD11bCre /Arg1fl/fl mice had significantly reduced macrophage
      infiltration but had no effect on albuminuria compared with Arg1fl/fl mice after
      12 wk of streptozotocin-induced diabetes. These results indicate that selective
      inhibition of arginase-2 would be effective in preventing or ameliorating major
      features of diabetic renal injury.

PMID- 28446460
TI  - Inhibition of cholinergic neurotransmission by beta3-adrenoceptors depends on
      adenosine release and A1-receptor activation in human and rat urinary bladders.
AB  - The direct detrusor relaxant effect of beta3-adrenoceptor agonists as a primary
      mechanism to improve overactive bladder symptoms has been questioned. Among other
      targets, activation of beta3-adrenoceptors downmodulate nerve-evoked
      acetylcholine (ACh) release, but there is insufficient evidence for the presence
      of these receptors on bladder cholinergic nerve terminals. Our hypothesis is that
      adenosine formed from the catabolism of cyclic AMP in the detrusor may act as a
      retrograde messenger via prejunctional A1 receptors to explain inhibition of
      cholinergic activity by beta3-adrenoceptors. Isoprenaline (1 uM) decreased
      [3H]ACh release from stimulated (10 Hz, 200 pulses) human (-47 +/- 5%) and rat (
      38 +/- 1%) detrusor strips. Mirabegron (0.1 uM, -53 +/- 8%) and CL316,243 (1 uM, 
      37 +/- 7%) mimicked isoprenaline (1 uM) inhibition, and their effects were
      prevented by blocking beta3-adrenoceptors with L748,337 (30 nM) and SR59230A (100
      nM), respectively, in human and rat detrusor. Mirabegron and isoprenaline
      increased extracellular adenosine in the detrusor. Blockage of A1 receptors with
      1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 100 nM) or the equilibrative
      nucleoside transporters (ENT) with dipyridamole (0.5 uM) prevented mirabegron and
      isoprenaline inhibitory effects. Dipyridamole prevented isoprenaline-induced
      adenosine outflow from the rat detrusor, and this effect was mimicked by the ENT1
      inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI, 30 uM). Cystometry recordings
      in anesthetized rats demonstrated that SR59230A, DPCPX, dipyridamole, and NBTI
      reversed the decrease in the voiding frequency caused by isoprenaline (0.1-1,000
      nM). Data suggest that inhibition of cholinergic neurotransmission by beta3
      adrenoceptors results from adenosine release via equilibrative nucleoside
      transporters and prejunctional A1-receptor stimulation in human and rat urinary
      bladder.

PMID- 28446461
TI  - Developmental changes in contractile responses to cholinergic stimuli: role of
      calcium sensitization and related pathways.
AB  - This study was performed to analyze the developmental changes in bladder response
      to cholinergic stimulation in detail, highlighting calcium sensitization (CS) and
      its related pathways. Rats were divided into three groups in accordance with
      reported time of developmental milestones (newborns, days 1-4; youngsters, days 5
      14; and grown-ups, days 15-28). Following cholinergic stimulation (carbachol, 5
      uM), the contractile response to detrusor was analyzed with respect to three
      phases (initial phasic, tonic, and superimposed phasic contractions). Contractile
      responses were analyzed by their dynamic and kinetic aspects. The responses were
      further compared in varying external calcium concentrations and in the presence
      of inhibitors of protein kinase C (PKC) and Rho kinase (ROCK), which are involved
      in CS. The responses of newborns contrasted with the others by their short and
      brisk initial phasic contractions, prominent tonic contractions, and delayed
      participation of irregular superimposed phasic contractions. With development,
      phasic contractions became prominent, and tonic contractions diminished. These
      developmental changes in phasic contractions were reproduced when exposed to
      increasing calcium concentrations. Application of specific inhibitors and
      molecular phasic analysis revealed that PKC was functional in tonic contractions
      of the newborns, whereas ROCK took over its role with development. Within a few
      days of birth, rats' bladders experienced drastic changes in contractile
      mechanisms. This included dominance of phasic contractions over tonic
      contractions due to increased calcium dependence and the maturational shift of
      the calcium sensitivity mechanism from PKC to ROCK.

PMID- 28446462
TI  - Sodium storage in human tissues is mediated by glycosaminoglycan expression.
AB  - The current paradigm regarding sodium handling in animals and humans postulates
      that total body sodium is regulated predominately via regulation of extracellular
      volume. Active sodium storage independent of volume retention is thought to be
      negligible. However, studies in animals, hypertensive patients, and healthy
      humans suggest water-free storage of sodium in skin. We hypothesized that tissue
      sodium concentrations ([Na]T) found in humans vary and reflect regulation due to
      variable glycosaminoglycan content due to variable expression of XYLT-1. Twenty
      seven patients on dialysis and 21 living kidney transplant donors free of
      clinically detectable edema were studied. During surgery, abdominal skin, muscle,
      and arteries were biopsied. [Na]T was determined by inductively coupled plasma
      optical emission spectrometry, semiquantitative glycosaminoglycan content with
      Alcian stain, and XYLT-1 expression by real-time PCR. [Na]T of arteries were
      ranging between 0.86 and 9.83 g/kg wet wt and were significantly higher in
      arteries (4.52 +/- 1.82 g/kg) than in muscle (2.03 +/- 1.41 g/kg; P < 0.001) or
      skin (3.24 +/- 2.26 g/kg wet wt; P = 0.038). For individual patients [Na]T
      correlated for skin and arterial tissue (r = 0.440, P = 0.012). [Na]T also
      correlated significantly with blinded semiquantitative analysis of
      glycosaminoglycans staining (r = 0.588, P = 0.004). In arteries XYLT-1 expression
      was also correlated with [Na]T (r = 0.392, P = 0.003). Our data confirm highly
      variable [Na]T in human skin and muscle and extend this observation to [Na]T in
      human arteries. These data support the hypothesis of water-independent sodium
      storage via regulated glycosaminoglycan synthesis in human tissues, including
      arteries.

PMID- 28446463
TI  - The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the
      Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity.
AB  - To date, over 100 small-molecule oncology drugs have been approved by the FDA.
      Because of the inherent heterogeneity of tumors, these small molecules are often
      administered in combination to prevent emergence of resistant cell
      subpopulations. Therefore, new combination strategies to overcome drug resistance
      in patients with advanced cancer are needed. In this study, we performed a
      systematic evaluation of the therapeutic activity of over 5,000 pairs of FDA
      approved cancer drugs against a panel of 60 well-characterized human tumor cell
      lines (NCI-60) to uncover combinations with greater than additive growth
      inhibitory activity. Screening results were compiled into a database, termed the
      NCI-ALMANAC (A Large Matrix of Anti-Neoplastic Agent Combinations), publicly
      available at https://dtp.cancer.gov/ncialmanac Subsequent in vivo experiments in
      mouse xenograft models of human cancer confirmed combinations with greater than
      single-agent efficacy. Concomitant detection of mechanistic biomarkers for these
      combinations in vivo supported the initiation of two phase I clinical trials at
      the NCI to evaluate clofarabine with bortezomib and nilotinib with paclitaxel in
      patients with advanced cancer. Consequently, the hypothesis-generating NCI
      ALMANAC web-based resource has demonstrated value in identifying promising
      combinations of approved drugs with potent anticancer activity for further
      mechanistic study and translation to clinical trials. Cancer Res; 77(13); 3564
      76. (c)2017 AACR.

PMID- 28446464
TI  - tRF/miR-1280 Suppresses Stem Cell-like Cells and Metastasis in Colorectal Cancer.
AB  - Several studies have shown that tRNAs can be enzymatically cleaved to generate
      distinct classes of tRNA-derived fragments (tRF). Here, we report that tRF/miR
      1280, a 17-bp fragment derived from tRNALeu and pre-miRNA, influences Notch
      signaling pathways that support the function of cancer stem-like cells (CSC) in
      colorectal cancer progression. tRF/miR-1280 expression was decreased in human
      specimens of colorectal cancer. Ectopic expression of tRF/miR-1280 reduced cell
      proliferation and colony formation, whereas its suppression reversed these
      effects. Mechanistic investigations implicated the Notch ligand JAG2 as a direct
      target of tRF/miR-1280 binding through which it reduced tumor formation and
      metastasis. Notably, tRF/miR-1280-mediated inactivation of Notch signaling
      suppressed CSC phenotypes, including by direct transcriptional repression of the
      Gata1/3 and miR-200b genes. These results were consistent with findings of
      decreased levels of miR-200b and elevated levels of JAG2, Gata1, Gata3, Zeb1, and
      Suz12 in colorectal cancer tissue specimens. Taken together, our results
      established that tRF/miR-1280 suppresses colorectal cancer growth and metastasis
      by repressing Notch signaling pathways that support CSC phenotypes. Furthermore,
      they provide evidence that functionally active miRNA can be derived from tRNA,
      offering potential biomarker and therapeutic uses. Cancer Res; 77(12); 3194-206.
      (c)2017 AACR.

PMID- 28446465
TI  - Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity.
AB  - Immunometabolism is emerging as a critical determinant of cancer pathophysiology.
      In this study, we explored the contributions of macrophage-expressed lactate
      dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung
      carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of
      macrophages with a CD86high and MCP-1high M1-like phenotype that suppressed tumor
      growth. This phenotypic effect was accompanied by reduced VEGF expression and
      angiogenesis, diminished numbers of PD-L1+ cancer cells, increased numbers of
      CD3+ T cells, and activation status of CD8+ T cells. Furthermore, it was
      associated with more pronounced antitumor T-cell immunity via induction of IL17
      and IFNgamma-producing CD8+ T (Tc17 and Tc1) cells, likely via suppression of
      lactate-driven PD-L1 expression. Our results suggest that expressions of LDH-A
      and lactate by macrophage in the tumor microenvironment are major drivers of T
      cell immunosuppression, strongly supporting the concept of targeting stromal LDH
      A as an effective strategy to blunt tumoral immune escape. Cancer Res; 77(13);
      3632-43. (c)2017 AACR.

PMID- 28446467
TI  - Para-bile-osis Establishes a Role for Nonbiliary Macrophage to Feces Reverse
      Cholesterol Transport.

PMID- 28446466
TI  - Landscape of Combination Immunotherapy and Targeted Therapy to Improve Cancer
      Management.
AB  - Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted
      drugs might improve cancer management, but there has been little investigation of
      their combined potential as yet. To estimate the fraction of cancer cases that
      might benefit from such combination therapy, we conducted an exploratory study of
      cancer genomic datasets to determine the proportion with somatic mutation
      profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349
      genomic profiles from public databases for cases with specific mutations targeted
      by current agents or a burden of exome-wide nonsynonymous mutations (NsM) that
      exceed a proposed threshold for response to checkpoint inhibitors. Overall, 8.9%
      of cases displayed profiles that could benefit from combination therapy, which
      corresponded to approximately 11.2% of U.S. annual incident cancer cases.
      Frequently targetable mutations were in PIK3CA, BRAF, NF1, NRAS, and PTEN We also
      noted a high burden of NsM in cases with targetable mutations in SMO, DDR2,
      FGFR1, PTCH1, FGFR2, and MET Our results indicate that a significant proportion
      of solid tumor patients are eligible for immuno-targeted combination therapy, and
      they suggest prioritizing specific cancers for trials of certain targeted and
      checkpoint inhibitor drugs. Cancer Res; 77(13); 3666-71. (c)2017 AACR.

PMID- 28446468
TI  - What's the Skinny on Elastin Deficiency and Supravalvular Aortic Stenosis?

PMID- 28446470
TI  - ATVB Named Lecture Review-Insight Into Author: Klaus Ley.

PMID- 28446469
TI  - Anticoagulation for Mechanical Heart Valves: Will Oral Factor Xa Inhibitors Be
      Effective?

PMID- 28446471
TI  - ATVB Named Lecture Review-Insight Into Author: Hiroaki Shimokawa.

PMID- 28446472
TI  - ATVB Named Lecture Review-Insight Into Author: Christopher K. Glass.

PMID- 28446473
TI  - Reactive Oxygen Species Generation and Atherosclerosis.

PMID- 28446474
TI  - Letter by Westerink and Visseren Regarding Article, "Ezetimibe in Combination
      With Statins Ameliorates Endothelial Dysfunction in Coronary Arteries After
      Stenting: The CuVIC Trial (Effect of Cholesterol Absorption Inhibitor Usage on
      Target Vessel Dysfunction After Coronary Stenting), a Multicenter Randomized
      Controlled Trial".

PMID- 28446475
TI  - Response by Takase and Matoba to Letter Regarding Article, "Ezetimibe in
      Combination With Statins Ameliorates Endothelial Dysfunction in Coronary Arteries
      After Stenting: The CuVIC Trial (Effect of Cholesterol Absorption Inhibitor Usage
      on Target Vessel Dysfunction After Coronary Stenting), a Multicenter Randomized
      Controlled Trial".

PMID- 28446476
TI  - Letter by Menzaghi et al Regarding Article, "Plasma Levels of Fatty Acid-Binding
      Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and
      Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective
      Study".

PMID- 28446478
TI  - Correction to: Telomerase Reverse Transcriptase Deficiency Prevents Neointima
      Formation Through Chromatin Silencing of E2F1 Target Genes.

PMID- 28446477
TI  - Response by Liu and Sun to Letter Regarding Article, "Plasma Levels of Fatty Acid
      Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin,
      and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year
      Prospective Study".

PMID- 28446479
TI  - Severe chronic diarrhoea secondary to primary lymph node gastrinoma.
AB  - The existence of primary lymph node (LN) gastrinoma is questionable and
      controversial. In fact, the presence of gastrinoma in such uncommon site raises
      the possibility of metastasis from another occult primary site. An extensive
      evaluation and careful follow-up is always warranted. A female aged 48 years
      presented with chronic abdominal pain and watery diarrhoea. Her serum gastrin and
      chromogranin were elevated, and an underlying gastrinoma was suspected. Further
      evaluation with an octreotide scan, an endoscopic ultrasound and a secretin
      stimulation test confirmed the diagnosis. Further evaluation for multiple
      endocrine neoplasia-1 syndrome was negative. She underwent a surgical enucleation
      near the head of the pancreas. No other lesions were found after careful
      exploration of the gastrinoma triangle. Histology showed a LN with a
      neuroendocrine tumour that tested positively with gastrin and chromogranin
      stains. Her symptoms resolved postoperatively, her serum gastrin normalised and a
      repeated octreotide scan was negative.

PMID- 28446480
TI  - Unusual cause for testicular swelling in a child.
AB  - Myeloid sarcoma is a rare solid tumour composed of primitive precursors of
      granulocytic series of white blood cells involving extramedullary anatomic site.
      Here we report the case of a 10-month-old with testicular swelling, who was
      finally diagnosed with granulocytic sarcoma. This case demonstrates that
      Granulocytic sarcoma should be considered as a part of the differential diagnosis
      for testicular swelling in spite of having normal peripheral counts and absence
      of hepatosplenomegaly.

PMID- 28446481
TI  - Alveolar soft part sarcoma presenting with back pain.

PMID- 28446482
TI  - Secondary parkinsonism in a patient of psychogenic polydipsia.
AB  - A 44-year-old man presented with history of slurring of speech, slowness in
      activities, abnormal posturing of the upper limbs and drooling of saliva from the
      mouth. He had a 5-yearlong history of compulsive water drinking, consuming 12-15
      L of water every day. He was earlier evaluated for the same and found to have low
      serum sodium (126 mEq/L). Presently, he was admitted at a primary care facility
      with fever and altered sensorium. He was found to have serum sodium of 94 mEq/L.
      His sensorium improved with hypertonic saline infusion; however, after a lucid
      interval of 48 hours, he developed florid extrapyramidal symptoms. Contrast
      enhanced MRI brain revealed bilaterally symmetric T2-weighted fluid-attenuated
      inversion recovery hyperintensity in caudate and lentiform nuclei. A diagnosis of
      extrapontine myelinolysis with secondary parkinsonism was made. He improved
      significantly with levodopa therapy.Psychogenic polydipsia is an important cause
      of hyponatraemia. Overzealous correction of hyponatraemia can be
      counterproductive.

PMID- 28446483
TI  - Spontaneous ruptured iliac artery aneurysm causing acute secondary AV fistula.
AB  - A 73-year-old woman presented with a 6-hour history of sudden onset lower
      abdominal pain. Her comorbidities included chronic obstructive pulmonary disease
      and hypertension. She was under surveillance for a known thoracoabdominal
      aneurysm. On presentation, she was hypotensive with a systolic blood pressure of
      50 mm Hg and a pulse of 60 beats per minute. On examination, she had a pulsatile
      mass with bruit in her right lower abdomen. Pedal pulses were palpable in both
      feet. Blood gas analysis revealed a metabolic acidosis with a pH of 7.21 and a
      lactate of 7.1. Haemoglobin remained stable between 90-100 g/dL. Her other
      routine blood tests were unremarkable, and blood cultures were negative. Imaging
      showed a ruptured right common iliac artery aneurysm into the right common iliac
      vein with secondary arteriovenous fistula communication. Surgical intervention
      was discussed with the patient but due to her frailty, it was deemed not in the
      patient's best interests.

PMID- 28446484
TI  - Cystic artery pseudoaneurysm following acute necrotising pancreatitis.
AB  - Cystic artery pseudoaneurysm is a rare pathology. Of the 20 cases reported so
      far, chronic cholecystitis and iatrogenic biliary injury form the majority of
      causes. Currently, there is no published report of such pseudoaneurysms caused
      secondary to pancreatitis, hence the management in such a scenario is unclear. We
      hereby present the first such report of cystic artery pseudoaneurysm occurring as
      a sequel of acute necrotising pancreatitis. A 33-year-old man who recovered from
      a recent attack of acute pancreatitis was readmitted for melena and fever.
      Computed tomography of abdomen revealed blood in the gall bladder with
      pericholecystic blush and resolving pancreatic necrosis. Percutaneous
      transarterial embolisation of the cystic artery was done. This stabilised the
      patient but persistent sepsis and clinical deterioration warranted a surgical
      exploration and cholecystostomy. Hence, transarterial embolisation followed by
      surgery in selected cases can be an ideal management protocol.

PMID- 28446485
TI  - Primary aortojejunal fistula: a rare cause for massive upper gastrointestinal
      bleeding.
AB  - A 68-year-old man presented to the emergency department with haematemesis and
      shock. Upper endoscopy and selective angiography could not identify the source of
      bleeding. He underwent selective embolisation of the gastroduodenal artery. The
      patient then had a period of about 24 hours with relative haemodynamic stability
      before having another episode of massive upper gastrointestinal bleed. A second
      attempt to embolise the common hepatic artery and distal coeliac axis was
      unsuccessful. Hence, he was urgently taken to the operating room for exploratory
      laparotomy. The source of bleeding could not be identified in the operating room.
      The patient went into cardiac arrest and expired. Autopsy revealed a fistula
      between proximal jejunum and a previously unknown abdominal aortic aneurysm
      (AAA). We present an entity that has only been described a few times in the
      literature while highlighting the importance of having a broad differential with
      upper gastrointestinal bleeding, especially when the source is not clearly
      evident.

PMID- 28446486
TI  - Delayed diagnosis of pulmonary tuberculosis in a 13-year-old Malawian boy.
AB  - Childhood tuberculosis (TB) is a significant global health burden. There are more
      than 1 million new cases of childhood TB annually. Despite this, many national TB
      control programs largely focus on identification and treatment of smear positive
      adults. Early case detection is essential if childhood TB is to be controlled and
      eradicated.Delayed diagnosis of TB is associated with more advanced disease and
      worse treatment outcomes. Younger children who go undiagnosed for long periods
      are at risk of developing severe pulmonary and extrapulmonary disease, such as
      meningitis. Additionally, advanced childhood TB is a common respiratory cause of
      death in TB-endemic areas. Undoubtedly, delayed diagnosis contributes
      significantly to TB-related morbidity and mortality.Diagnostic delay may be
      divided into patient delay, the duration between development of symptoms and
      presentation to healthcare provider, and healthcare provider delay, the duration
      between presentation and initiation of appropriate treatment.

PMID- 28446487
TI  - Haemophagocytic lymphohistiocytosis as a consequence of untreated B-cell chronic
      lymphocytic leukaemia.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome
      characterised by defective cytotoxic function and hypercytokinaemia leading to
      macrophage expansion and haemophagocytosis. Patients often present with
      unexplained fevers, hepatosplenomegaly and pancytopenia, with elevation in serum
      ferritin and triglyceride. Acquired forms are triggered by infection, malignancy
      or rheumatological disorders. HLH in the setting of chronic lymphocytic leukaemia
      is rarely reported, however, and is usually associated with infection or as a
      consequence of chemotherapy. We present a case of HLH in a 64-year-old Caucasian
      woman with the only identified trigger being her hitherto untreated CLL.

PMID- 28446489
TI  - Revisiting propafenone toxicity.
AB  - Propafenone is a Vaughan Williams class 1c antiarrhythmic medication widely used
      for treatment of arrhythmias. Although the long-term safety of propafenone use
      has not been established, it is commonly used for treatment of atrial
      fibrillation in patients with no structural heart disease. Propafenone is well
      known as pill-in-the-pocket treatment for its effect in terminating paroxysmal
      episodes of atrial fibrillation. Herein, we discuss an unusual adverse reaction
      to propafenone in a patient who presented with symptomatic bradycardia and
      hypotension. The aim of this article is to increase physician awareness for
      propafenone toxicity and its management, with a focused literature review on
      propafenone pharmacotherapy.

PMID- 28446488
TI  - Eculizumab in a child with atypical haemolytic uraemic syndrome and
      haemophagocytic lymphohistiocytosis triggered by cytomegalovirus infection.
AB  - We present the case of a 21-month-old girl with two rare and life-threatening
      conditions, atypical haemolytic uraemic syndrome (aHUS) and haemophagocytic
      lymphohistiocytosis (HLH), triggered by a cytomegalovirus (CMV) infection. Soon
      after admission, the girl became anuric and required continuous venovenous
      haemodiafiltration.Initial treatments included methylprednisolone, fibrinogen and
      plasma infusion (for HLH), plasmapheresis (for thrombotic microangiopathy),
      immunoglobulins (for inflammation), ganciclovir (for CMV infection) and the
      antibiotic cefotaxime. On day 5, eculizumab (600 mg) was given for aHUS, with
      rapid improvement in haematological and nephrological parameters. Despite a
      subsequent isolated episode of right heart thrombosis that resolved with heparin
      treatment, the patient showed a favourable response to eculizumab (300 mg/15
      days), with improved renal function, normal haematological values, and no
      treatment complications. In conclusion, eculizumab effectively treated aHUS in
      this case despite a comorbid immunological disease.

PMID- 28446490
TI  - Complicated acute cerebellitis with obstructive hydrocephalus and tonsillar
      herniation in a child.
AB  - Acute cerebellitis (AC) is a rare inflammatory syndrome presenting as cerebellar
      dysfunction, seen more frequently in children. AC can have a variable course with
      features of cerebellar dysfunction, raised intracranial pressure and neurological
      deficits, and can sometimes even be potentially fatal due to complications such
      as obstructive hydrocephalus and brainstem compression, warranting surgical
      intervention. We report a case of a 12-year-old boy who presented with raised
      intracranial pressure and ataxia. Imaging with CT and MRI showed AC with
      obstructive hydrocephalus and tonsillar herniation. He was managed with
      medications for raised intracranial pressure and with ventriculoperitoneal shunt,
      and he recovered completely over a period of 2 weeks. Imaging has an important
      role in the diagnosis of AC and in differentiating it from acute cerebellar
      ataxia, which has a more benign course. It is crucial to diagnose and promptly
      manage the rarely occurring but life-threatening complications of AC.

PMID- 28446491
TI  - Pure form of Ackermann's tumour of the tongue in a young female patient.

PMID- 28446492
TI  - Hepatic Fibrosis Is Universal Following Fontan Operation, and Severity is
      Associated With Time From Surgery: A Liver Biopsy and Hemodynamic Study.
AB  - BACKGROUND: Congestive hepatopathy is a recognized complication of Fontan
      physiology. Data regarding the incidence of hepatopathy and risk factors are
      lacking. METHODS AND RESULTS: Liver biopsies and cardiac catherizations were
      performed as part of an evaluation offered to all patients >=10 years after
      Fontan. Quantitative determination of hepatic fibrosis was performed using Sirius
      red staining with automated calculation of collagen deposition per slide (%CD).
      Biopsies from included subjects were compared to stained specimens from controls
      without known fibrotic liver disease. Patient characteristics, echocardiographic
      findings, and hemodynamic measures were evaluated as potential risk factors. The
      cohort consisted of 67 patients (31 female) at mean age of 17.3+/-4.5 years and
      mean time from Fontan of 14.9+/-4.5 years. Right ventricular morphology was
      present in 37 subjects. Median %CD by Sirius red staining was 21.6% (range 8.7%
      to 49.4%) compared to 2.6% (range 2.2% to 3.0%) in controls. There was a
      significant correlation between time from Fontan and degree of Sirius red
      staining (r=0.33, P<0.01). Serum liver enzymes and platelet count did not
      correlate with %CD. The median inferior vena cava pressure was 13 mm Hg (range 6
      24 mm Hg) and did not correlate with %CD. There was no difference in %CD based on
      ventricular morphology or severity of atrioventricular valve insufficiency.
      CONCLUSIONS: In this cohort of predominantly asymptomatic children and
      adolescents electively evaluated after a Fontan operation, all exhibited evidence
      for hepatic fibrosis as measured by collagen deposition in the liver. Time from
      Fontan was the only factor significantly associated with collagen deposition.
      These findings demonstrate that liver fibrosis is an inherent feature of Fontan
      physiology and that the degree of fibrosis increases over time.

PMID- 28446493
TI  - Hospital Performance on Percutaneous Coronary Intervention Process and Outcomes
      Measures.
AB  - BACKGROUND: The Physician Consortium for Performance Improvement recently
      proposed percutaneous coronary intervention (PCI)-specific process measures.
      However, information about hospital performance on these measures and the
      association of PCI process and outcomes measures are not available. METHODS AND
      RESULTS: We linked the National Cardiovascular Data Registry (NCDR) CathPCI
      Registry with Medicare claims data to assess hospital performance on established
      PCI process measures (aspirin, thienopyridines, and statins on discharge; door-to
      balloon time; and referral to cardiac rehabilitation), newly proposed PCI process
      measures (documentation of contrast dose, glomerular filtration rate, and PCI
      indication; appropriate indication for elective PCI; and use of embolic
      protection device), and a composite of all process measures. We calculated
      weighted pair-wise correlations between each set of process metrics and performed
      weighted correlation analyses to assess the association between composite measure
      performance with corresponding 30-day risk-standardized mortality and readmission
      rates. We reported the variance in risk-standardized 30-day outcome rates
      explained by process measures. We analyzed 1 268 860 PCIs from 1331 hospitals.
      For many process measures, median hospital performance exceeded 90%. We found
      strong correlations between medication-specific process measures (P<0.01) and
      weak correlations between hospital performance on the newly proposed and
      established process measures. The composite process measure explained only 1.3%
      and 2.0% of the observed variation in mortality and readmission rates,
      respectively. CONCLUSIONS: Hospital performance on many PCI-specific process
      measures demonstrated little opportunity for improvement and explained only a
      small percentage of hospital variation in 30-day outcomes. Efforts to measure and
      improve hospital quality for PCI patients should focus on both process and
      outcome measures.

PMID- 28446494
TI  - Effects of the Mean Amplitude of Glycemic Excursions and Vascular Endothelial
      Dysfunction on Cardiovascular Events in Nondiabetic Patients With Coronary Artery
      Disease.
AB  - BACKGROUND: Mean amplitude of glycemic excursion (MAGE) is commonly used to gauge
      the degree of glucose level fluctuations. MAGE plays a significant role in
      vascular endothelial dysfunction and cardiovascular events in patients with
      diabetes mellitus (DM), but its significance is not clear in non-DM patients.
      Thus, we examined the impact of MAGE and vascular endothelial dysfunction on
      clinical outcomes in non-DM patients with coronary artery disease. METHODS AND
      RESULTS: We followed non-DM patients (n=65) for 12 months who underwent
      percutaneous coronary intervention and assessed the relationship among MAGE,
      reactive hyperemia index (RHI) measured by reactive hyperemia peripheral arterial
      tonometry as endothelial function, and cardiovascular events. Cardiovascular
      events analyzed were cardiovascular death, myocardial infarction, unstable
      angina, and revascularizations. Compared with patients with MAGE <65 mg/dL
      (normal glycemic excursions), the group with MAGE >=65 mg/dL (high glycemic
      excursions) had significantly higher high-sensitivity C-reactive protein (0.10+/
      0.11 mg/dL versus 0.18+/-0.13 mg/dL, P=0.006) and lower RHI (0.64+/-0.21 versus
      0.51+/-0.22, P=0.035). The multivariable analysis identified high MAGE and low
      RHI (<=0.56) as risk factors associated with cardiovascular events (hazard ratio,
      5.6; 95% RI, 1.72-18.4 [P=0.004] versus hazard ratio, 4.5; 95% RI, 1.37-14.9
      [P=0.013]). When the prognosis was classified by combination with MAGE and RHI,
      the incidence of cardiovascular events was 46.7% (high MAGE+low RHI), 26.7% (high
      MAGE+high RHI), 20.0% (low MAGE+low RHI), and 6.6% (low MAGE+high RHI) in
      descending order (P=0.014). Receiver operating characteristic curve analysis
      revealed that MAGE, RHI, and MAGE+RHI were each associated with cardiovascular
      events (area under the curve 0.780, 0.727, and 0.796, respectively). CONCLUSIONS:
      MAGE was associated with cardiovascular events in non-DM patients with coronary
      artery disease. Furthermore, the combination with MAGE and RHI was useful for
      further subdivision of the risk of cardiovascular events.

PMID- 28446495
TI  - Randomized Controlled Trial of High-Volume Energy Drink Versus Caffeine
      Consumption on ECG and Hemodynamic Parameters.
AB  - BACKGROUND: Caffeine in doses <400 mg is typically not considered arrhythmogenic,
      but little is known about the additional ingredients in energy drinks. We
      evaluated the ECG and blood pressure (BP) effects of high-volume energy drink
      consumption compared with caffeine alone. METHODS AND RESULTS: This was a
      randomized, double-blind, controlled, crossover study in 18 young, healthy
      volunteers. Participants consumed either 946 mL (32 ounces) of energy drink or
      caffeinated control drink, both of which contained 320 mg of caffeine, separated
      by a 6-day washout period. ECG, peripheral BP, and central BP measurements were
      obtained at baseline and 1, 2, 4, 6, and 24 hours post study drink consumption.
      The time-matched, baseline-adjusted changes were compared. The change in
      corrected QT interval from baseline in the energy drink arm was significantly
      higher than the caffeine arm at 2 hours (0.44+/-18.4 ms versus -10.4+/-14.8 ms,
      respectively; P=0.02). The QTc changes were not different at other time points.
      While both the energy drink and caffeine arms raised systolic BP in a similar
      fashion initially, the systolic BP was significantly higher at 6 hours when
      compared with the caffeine arm (4.72+/-4.67 mm Hg versus 0.83+/-6.09 mm Hg,
      respectively; P=0.01). Heart rate, diastolic BP, central systolic BP, and central
      diastolic BP showed no evidence of a difference between groups at any time point.
      Post energy drink, augmentation index was lower at 6 hours. CONCLUSIONS: The
      corrected QT interval and systolic BP were significantly higher post high-volume
      energy drink consumption when compared with caffeine alone. Larger clinical
      trials validating these findings and evaluation of noncaffeine ingredients within
      energy drinks are warranted. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT02023723.

PMID- 28446496
TI  - Mobile-based intervention intended to stop obesity in preschool-aged children:
      the MINISTOP randomized controlled trial.
AB  - Background: Traditional obesity prevention programs are time- and cost-intensive.
      Mobile phone technology has been successful in changing behaviors and managing
      weight; however, to our knowledge, its potential in young children has yet to be
      examined.Objective: We assessed the effectiveness of a mobile health (mHealth)
      obesity prevention program on body fat, dietary habits, and physical activity in
      healthy Swedish children aged 4.5 y.Design: From 2014 to 2015, 315 children were
      randomly assigned to an intervention or control group. Parents in the
      intervention group received a 6-mo mHealth program. The primary outcome was fat
      mass index (FMI), whereas the secondary outcomes were intakes of fruits,
      vegetables, candy, and sweetened beverages and time spent sedentary and in
      moderate-to-vigorous physical activity. Composite scores for the primary and
      secondary outcomes were computed.Results: No statistically significant
      intervention effect was observed for FMI between the intervention and control
      group (mean +/- SD: -0.23 +/- 0.56 compared with -0.20 +/- 0.49 kg/m2). However,
      the intervention group increased their mean composite score from baseline to
      follow-up, whereas the control group did not (+0.36 +/- 1.47 compared with -0.06
      +/- 1.33 units; P = 0.021). This improvement was more pronounced among the
      children with an FMI above the median (4.11 kg/m2) (P = 0.019). The odds of
      increasing the composite score for the 6 dietary and physical activity behaviors
      were 99% higher for the intervention group than the control group (P =
      0.008).Conclusions: This mHealth obesity prevention study in preschool-aged
      children found no difference between the intervention and control group for FMI.
      However, the intervention group showed a considerably higher postintervention
      composite score (a secondary outcome) than the control group, especially in
      children with a higher FMI. Further studies targeting specific obesity classes
      within preschool-aged children are warranted. This trial was registered at
      clinicaltrials.gov as NCT02021786.

PMID- 28446497
TI  - Best (but oft-forgotten) practices: mediation analysis.
AB  - This contribution in the "Best (but Oft-Forgotten) Practices" series considers
      mediation analysis. A mediator (sometimes referred to as an intermediate
      variable, surrogate endpoint, or intermediate endpoint) is a third variable that
      explains how or why >=2 other variables relate in a putative causal pathway. The
      current article discusses mediation analysis with the ultimate intention of
      helping nutrition researchers to clarify the rationale for examining mediation,
      avoid common pitfalls when using the model, and conduct well-informed analyses
      that can contribute to improving causal inference in evaluations of underlying
      mechanisms of effects on nutrition-related behavioral and health outcomes. We
      give specific attention to underevaluated limitations inherent in common
      approaches to mediation. In addition, we discuss how to conduct a power analysis
      for mediation models and offer an applied example to demonstrate mediation
      analysis. Finally, we provide an example write-up of mediation analysis results
      as a model for applied researchers.

PMID- 28446498
TI  - Diet quality of US adolescents during the transition to adulthood: changes and
      predictors.
AB  - Background: Influences on diet quality during the transition from adolescence to
      adulthood are understudied.Objective: This study examined association of 3 diet
      quality indicators-Healthy Eating Index-2010 (HEI), Whole Plant Foods Density
      (WPF), and Empty Calories (EC; the percentage of calories from discretionary
      solid fat, added sugar and alcohol)-with lifestyle behaviors, baseline weight
      status, and sociodemographic characteristics in US emerging adults.Design: Data
      come from the first 4 waves (annual assessments) of the NEXT Plus Study, a
      population-based cohort of 10th graders enrolled in 2010 (n = 566). At each
      assessment, participants completed 3 nonconsecutive 24-h diet recalls, wore
      accelerometers for 7 d, and self-reported meal practices and sedentary behaviors.
      Self-reported sociodemographic characteristics were ascertained at baseline.
      Generalized estimating equations examined associations of time-varying diet
      quality with baseline weight status and sociodemographic characteristics and time
      varying lifestyle behaviors.Results: Diet quality improved modestly from baseline
      (mean +/- SE: HEI, 44.07 +/- 0.53; WPF, 1.24 +/- 0.04; and EC, 35.66 +/- 0.55) to
      wave 4 for WPF (1.44 +/- 0.05, P < 0.001) and EC (33.47 +/- 0.52, P < 0.001), but
      not HEI (45.22 +/- 0.60). In longitudinal analyses, higher HEI and lower EC
      scores were observed in Hispanic compared with white participants. Better diet
      quality was associated with greater moderate-to-vigorous physical activity, more
      frequent breakfast and family meals, less frequent fast food and meals during
      television viewing, and shorter durations of television viewing, gaming, and
      online social networking. Diet-quality indicators were not consistently
      associated with time-varying physical inactivity, baseline weight status, or
      sociodemographic characteristics.Conclusions: Diet quality of emerging adults in
      the US remained suboptimal, but some aspects improved marginally over the 4-y
      study period. Meal contexts and sedentary behaviors may represent important
      intervention targets. There is substantial room for improvement in diet quality
      in all sociodemographic subgroups. This trial was registered at
      clinicaltrials.gov as NCT01031160.

PMID- 28446499
TI  - Food groups and risk of all-cause mortality: a systematic review and meta
      analysis of prospective studies.
AB  - Background: Suboptimal diet is one of the most important factors in preventing
      early death and disability worldwide.Objective: The aim of this meta-analysis was
      to synthesize the knowledge about the relation between intake of 12 major food
      groups, including whole grains, refined grains, vegetables, fruits, nuts,
      legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened
      beverages, with risk of all-cause mortality.Design: We conducted a systematic
      search in PubMed, Embase, and Google Scholar for prospective studies
      investigating the association between these 12 food groups and risk of all-cause
      mortality. Summary RRs and 95% CIs were estimated with the use of a random
      effects model for high-intake compared with low-intake categories, as well as for
      linear and nonlinear relations. Moreover, the risk reduction potential of foods
      was calculated by multiplying the RR by optimal intake values (serving category
      with the strongest association) for risk-reducing foods or risk-increasing foods,
      respectively.Results: With increasing intake (for each daily serving) of whole
      grains (RR: 0.92; 95% CI: 0.89, 0.95), vegetables (RR: 0.96; 95% CI: 0.95, 0.98),
      fruits (RR: 0.94; 95% CI: 0.92, 0.97), nuts (RR: 0.76; 95% CI: 0.69, 0.84), and
      fish (RR: 0.93; 95% CI: 0.88, 0.98), the risk of all-cause mortality decreased;
      higher intake of red meat (RR: 1.10; 95% CI: 1.04, 1.18) and processed meat (RR:
      1.23; 95% CI: 1.12, 1.36) was associated with an increased risk of all-cause
      mortality in a linear dose-response meta-analysis. A clear indication of
      nonlinearity was seen for the relations between vegetables, fruits, nuts, and
      dairy and all-cause mortality. Optimal consumption of risk-decreasing foods
      results in a 56% reduction of all-cause mortality, whereas consumption of risk
      increasing foods is associated with a 2-fold increased risk of all-cause
      mortality.Conclusion: Selecting specific optimal intakes of the investigated food
      groups can lead to a considerable change in the risk of premature death.

PMID- 28446501
TI  - Dietary long-chain fatty acids and carbohydrate biomarker evaluation in a
      controlled feeding study in participants from the Women's Health Initiative
      cohort.
AB  - Background: Biomarkers of macronutrient intake are lacking. Controlled human
      feeding studies that preserve the normal variation in nutrient and food
      consumption are necessary for the development and validation of robust
      nutritional biomarkers.Objective: We aimed to assess the utility of serum
      phospholipid fatty acids (PLFAs) as biomarkers of dietary intakes of fatty acids,
      total fat, and carbohydrate.Design: We used an individualized controlled feeding
      study in which 153 postmenopausal women from the Women's Health Initiative (WHI)
      were provided with a 2-wk controlled diet that mimicked each individual's
      habitual food intake. A total of 41 PLFAs were measured with the use of gas
      chromatography in end-of-feeding-period fasting serum samples and expressed in
      both relative and absolute concentrations. R2 values (percentages of variation
      explained) from linear regressions of (ln-transformed) consumed fatty acids
      (individual, groups, and broad categories) on (ln-transformed) corresponding
      measures of serum PLFAs alone and together with selected participant-related
      variables (age, race/ethnicity, body mass index, season of study participation,
      education level, and estimated energy intake from doubly labeled water) were used
      for evaluation against established urinary recovery biomarkers of energy and
      protein intake as benchmarks. Models to predict intakes of other nutrients were
      also explored.Results: Intakes of eicosapentaenoic acid and docosahexaenoic acid
      achieved the benchmark of R2 > 36% with or without covariates. When all 41 serum
      PLFAs and participant-related covariates were initially included in the model for
      selection, cross-validated R2 achieved >36% for consumed total carbohydrate
      (grams per day), total saturated fatty acids (SFAs), percentage of energy from
      SFAs, and total trans fatty acids with serum PLFAs in both relative and absolute
      concentrations.Conclusions: Serum PLFA biomarkers perform similarly to
      established energy and protein urinary recovery biomarkers in describing intake
      variations for several nutrients and, thus, appear suitable for application in
      this population of postmenopausal women. This approach represents an important
      methodologic contribution toward the utilization of nutritional biomarkers to
      assess macronutrient intake. This trial was registered at clinicaltrials.gov as
      NCT00000611.

PMID- 28446500
TI  - Protective effect of homovanillyl alcohol on cardiovascular disease and total
      mortality: virgin olive oil, wine, and catechol-methylathion.
AB  - Background: Hydroxytyrosol is a phenolic compound that is present in virgin olive
      oil (VOO) and wine. Hydroxytyrosol-related foods have been shown to protect
      against cardiovascular disease (CVD).Objective: We investigated the associations
      between hydroxytyrosol and its biological metabolite, 3-O-methyl-hydroxytyrosol,
      also known as homovanillyl alcohol (HVAL), with CVD and total mortality.Design:
      We included 1851 men and women with a mean +/- SD age of 66.8 +/- 6 y at high
      risk of CVD from prospective cohort data. The primary endpoint was a composite of
      myocardial infarction, stroke, and death from cardiovascular causes; the
      secondary endpoint was all-cause mortality. Twenty-four-hour urinary
      hydroxytyrosol and HVAL and catechol-O-methyltransferase (COMT) rs4680 genotypes
      were measured.Results: After multivariable adjustment, all biomarkers were
      associated, as a continuous variable, with lower CVD risk, but only HVAL showed a
      strong inverse association (HR: 0.44; 95% CI: 0.25, 0.80) for the comparison
      between quintiles. Only HVAL, as a continuous variable, was associated with total
      mortality (HR: 0.81; 95% CI: 0.70, 0.95). Individuals in the highest quintile of
      HVAL compared with the lowest had 9.2 (95% CI: 3.5, 20.8) and 6.3 (95% CI: 2.3,
      12.1) additional years of life or years free of CVD, respectively, after 65 y.
      Individuals with the rs4680GG genotype had the highest HVAL concentrations (P =
      0.05). There was no association between COMT genotypes and events or interaction
      between COMT genotypes and HVAL concentrations.Conclusions: We report, for the
      first time to our knowledge, an independent association between high urinary HVAL
      concentrations and a lower risk of CVD and total mortality in elderly
      individuals. VOO and wine consumption and a high metabolic COMT capacity for
      methylation are key factors for high HVAL concentrations. The association that
      stems from our results reinforces the benefits of 2 key components of the
      Mediterranean diet (wine and VOO). This trial was registered at www.predimed.es
      as ISRCTN35739639.

PMID- 28446502
TI  - Correspondence of folate dietary intake and biomarker data.
AB  - Background: Public health concerns with regard to both low and high folate status
      exist in the United States. Recent publications have questioned the utility of
      self-reported dietary intake data in research and monitoring.Objectives: The
      purpose of this analysis was to examine the relation between self-reported folate
      intakes and folate status biomarkers and to evaluate their usefulness for several
      types of applications.Design: We examined usual dietary intakes of folate by
      using the National Cancer Institute method to adjust two 24-h dietary recalls
      (including dietary supplements) for within-person variation and then compared
      these intakes with serum and red blood cell (RBC) folate among 4878 men and
      nonpregnant, nonlactating women aged >=19 y in NHANES 2011-2012, a nationally
      representative, cross-sectional survey, with respect to consistency across
      prevalence estimates and rank order comparisons.Results: There was a very low
      prevalence (<1%) of folate deficiency when serum (<7 nmol/L) and RBC (<305
      nmol/L) folate were considered, whereas a higher proportion of the population
      reported inadequate total dietary folate intakes (6%). Similar patterns of change
      occurred between intakes and biomarkers of folate status when distributions were
      examined (i.e., dose response), particularly when diet was expressed in MUg.
      Intakes greater than the Tolerable Upper Intake Level greatly increased the odds
      of having high serum folate (OR: 17.6; 95% CI: 5.5, 56.0).Conclusions: When
      assessing folate status in the United States, where fortification and supplement
      use are common, similar patterns in the distributions of diet and biomarkers
      suggest that these 2 types of status indicators reflect the same underlying
      folate status; however, the higher prevalence estimates for inadequate intakes
      compared with biomarkers suggest, among other factors, a systematic
      underestimation bias in intake data. Caution is needed in the use of dietary
      folate data to estimate the prevalence of inadequacy among population groups. The
      use of dietary data for rank order comparisons or to estimate the potential for
      dietary excess is likely more reliable.

PMID- 28446503
TI  - Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional
      Metastatic Disease in Head and Neck Cancer.
AB  - Purpose: Comprehensive cervical lymphadenectomy can be associated with
      significant morbidity and poor quality of life. This study evaluated the
      sensitivity and specificity of cetuximab-IRDye800CW to identify metastatic
      disease in patients with head and neck cancer.Experimental Design: Consenting
      patients scheduled for curative resection were enrolled in a clinical trial to
      evaluate the safety and specificity of cetuximab-IRDye800CW. Patients (n = 12)
      received escalating doses of the study drug. Where indicated, cervical
      lymphadenectomy accompanied primary tumor resection, which occurred 3 to 7 days
      following intravenous infusion of cetuximab-IRDye800CW. All 471 dissected lymph
      nodes were imaged with a closed-field, near-infrared imaging device during gross
      processing of the fresh specimens. Intraoperative imaging of exposed neck levels
      was performed with an open-field fluorescence imaging device. Blinded assessments
      of the fluorescence data were compared to histopathology to calculate
      sensitivity, specificity, negative predictive value (NPV), and positive
      predictive value (PPV).Results: Of the 35 nodes diagnosed pathologically
      positive, 34 were correctly identified with fluorescence imaging, yielding a
      sensitivity of 97.2%. Of the 435 pathologically negative nodes, 401 were
      correctly assessed using fluorescence imaging, yielding a specificity of 92.7%.
      The NPV was determined to be 99.7%, and the PPV was 50.7%. When 37 fluorescently
      false-positive nodes were sectioned deeper (1 mm) into their respective blocks,
      metastatic cancer was found in 8.1% of the recut nodal specimens, which altered
      staging in two of those cases.Conclusions: Fluorescence imaging of lymph nodes
      after systemic cetuximab-IRDye800CW administration demonstrated high sensitivity
      and was capable of identifying additional positive nodes on deep sectioning. Clin
      Cancer Res; 23(16); 4744-52. (c)2017 AACR.

PMID- 28446504
TI  - Feasibility of Ultra-High-Throughput Functional Screening of Melanoma Biopsies
      for Discovery of Novel Cancer Drug Combinations.
AB  - Purpose: Successful development of targeted therapy combinations for cancer
      patients depends on first discovering such combinations in predictive preclinical
      models. Stable cell lines and mouse xenograft models can have genetic and
      phenotypic drift and may take too long to generate to be useful as a personalized
      medicine tool.Experimental Design: To overcome these limitations, we have used a
      platform of ultra-high-throughput functional screening of primary biopsies
      preserving both cancer and stroma cell populations from melanoma patients to
      nominate such novel combinations from a library of thousands of drug combinations
      in a patient-specific manner within days of biopsy. In parallel, patient-derived
      xenograft (PDX) mouse models were created and novel combinations tested for their
      ability to shrink matched PDXs.Results: The screening method identifies specific
      drug combinations in tumor cells with patterns that are distinct from those
      obtained from stable cell lines. Screening results were highly specific to
      individual patients. For patients with matched PDX models, we confirmed that
      individualized novel targeted therapy combinations could inhibit tumor growth. In
      particular, a combination of multi-kinase and PI3K/Akt inhibitors was effective
      in some BRAF-wild-type melanomas, and the addition of cediranib to the BRAF
      inhibitor PLX4720 was effective in a PDX model with BRAF mutation.Conclusions:
      This proof-of-concept study demonstrates the feasibility of using primary
      biopsies directly for combinatorial drug discovery, complementing stable cell
      lines and xenografts, but with much greater speed and efficiency. This process
      could potentially be used in a clinical setting to rapidly identify therapeutic
      strategies for individual patients. Clin Cancer Res; 23(16); 4680-92. (c)2017
      AACR.

PMID- 28446505
TI  - Clinical Features and Outcomes of Patients with Colorectal Cancers Harboring NRAS
      Mutations.
AB  - Purpose:NRAS mutations are now routinely included in RAS testing prior to EGFR
      inhibitor therapy for metastatic colorectal cancer (mCRC). The clinical
      implications of NRAS mutation beyond lack of response to anti-EGFR therapy,
      however, are not known. We undertook this study to determine the clinical
      features and treatment outcomes of patients with NRAS-mutant mCRC.Experimental
      Design: We reviewed clinical characteristics, concurrent mutations, and outcomes
      for all mCRC cases with NRAS mutations undergoing standard genotyping at our
      institution from 2008 to 2015. Comparison groups consisted of RAS wild-type and
      KRAS-mutant mCRC consecutive cases genotyped from 2008 to 2012.Results: Three
      percent (87/2764) of mCRC patients had NRAS-mutant tumors (45% exon 2 and 55%
      exon 3), including three cases with concurrent NRAS and KRAS mutations. Left
      sided primary site and African American self-reported race were associated with
      NRAS mutation (P < 0.01). Resection rate at 12 months was lower for NRAS-mutant
      mCRC than for RAS wild-type or KRAS-mutant mCRC. Median survival from time of
      first known metastasis was 33 months for NRAS-mutant, 47 months for KRAS-mutant,
      and 78 months for RAS wild-type cases (P < 0.001). Multivariate analysis assigned
      an HR for overall survival of 2.0 for NRAS mutation and 1.5 for KRAS mutation (P
      < 0.01).Conclusions:NRAS defines a molecular subset with distinct clinical
      characteristics from KRAS-mutant and wild-type mCRC. NRAS mutations are enriched
      in left-sided primary tumors and among African Americans. Mutations in NRAS are
      associated with poor survival and worse outcomes than either KRAS-mutant or wild
      type mCRC. Clin Cancer Res; 23(16); 4753-60. (c)2017 AACR.

PMID- 28446506
TI  - Analytic, Preanalytic, and Clinical Validation of p53 IHC for Detection of TP53
      Missense Mutation in Prostate Cancer.
AB  - Purpose:TP53 missense mutations may help to identify prostate cancer with lethal
      potential. Here, we preanalytically, analytically, and clinically validated a
      robust IHC assay to detect subclonal and focal TP53 missense mutations in
      prostate cancer.Experimental Design: The p53 IHC assay was performed in a CLIA
      accredited laboratory on the Ventana Benchmark immunostaining system. p53 protein
      nuclear accumulation was defined as any p53 nuclear labeling in >10% of tumor
      cells. Fifty-four formalin-fixed paraffin embedded (FFPE) cell lines from the NCI
      60 panel and 103 FFPE prostate cancer tissues (88 primary adenocarcinomas, 15
      metastases) with known TP53 mutation status were studied. DU145 and VCaP
      xenografts were subjected to varying fixation conditions to investigate the
      effects of preanalytic variables. Clinical validation was performed in two
      partially overlapping radical prostatectomy cohorts.Results: p53 nuclear
      accumulation by IHC was 100% sensitive for detection of TP53 missense mutations
      in the NCI-60 panel (25/25 missense mutations correctly identified). Lack of p53
      nuclear accumulation was 86% (25/29) specific for absence of TP53 missense
      mutation. In FFPE prostate tumors, the positive predictive value of p53 nuclear
      accumulation for underlying missense mutation was 84% (38/45), whereas the
      negative predictive value was 97% (56/58). In a cohort of men who experienced
      biochemical recurrence after RP, the multivariable HR for metastasis among cases
      with p53 nuclear accumulation compared with those without was 2.55 (95%
      confidence interval, 1.1-5.91).Conclusions: IHC is widely available method to
      assess for the presence of deleterious and heterogeneous TP53 missense mutations
      in clinical prostate cancer specimens. Clin Cancer Res; 23(16); 4693-703. (c)2017
      AACR.

PMID- 28446507
TI  - The Microbiota: A New Variable Impacting Cancer Treatment Outcomes.
AB  - Preclinical evidence has established that the host commensal microbiota can
      contribute to therapeutic response in cancer models, a finding supported by early
      clinical data. This connection between the microbiome and clinical outcome in
      oncology is cause for new consideration in the administration of antibiotics and
      microbiota-modulating interventions to improve outcomes. Clin Cancer Res; 23(13);
      3229-31. (c)2017 AACRSee related article by Galloway-Pena et al., p. 3263.

PMID- 28446509
TI  - Inhibition of the all-trans Retinoic Acid (atRA) Hydroxylases CYP26A1 and CYP26B1
      Results in Dynamic, Tissue-Specific Changes in Endogenous atRA Signaling.
AB  - All-trans retinoic acid (atRA), the active metabolite of vitamin A, is a ligand
      for several nuclear receptors and acts as a critical regulator of many
      physiologic processes. The cytochrome P450 family 26 (CYP26) enzymes are
      responsible for atRA clearance, and are potential drug targets to increase
      concentrations of endogenous atRA in a tissue-specific manner. Talarozole is a
      potent inhibitor of CYP26A1 and CYP26B1, and has shown some success in clinical
      trials. However, it is not known what magnitude of change is needed in tissue
      atRA concentrations to promote atRA signaling changes. The aim of this study was
      to quantify the increase in endogenous atRA concentrations necessary to alter
      atRA signaling in target organs, and to establish the relationship between CYP26
      inhibition and altered atRA concentrations in tissues. Following a single 2.5
      mg/kg dose of talarozole to mice, atRA concentrations increased up to 5.7-, 2.7-,
      and 2.5-fold in serum, liver, and testis, respectively, resulting in induction of
      Cyp26a1 in the liver and testis and Rar beta and Pgc 1beta in liver. The increase
      in atRA concentrations was well predicted from talarozole pharmacokinetics and in
      vitro data of CYP26 inhibition. After multiple doses of talarozole, a significant
      increase in atRA concentrations was observed in serum but not in liver or testis.
      This lack of increase in atRA concentrations correlated with an increase in
      CYP26A1 expression in the liver. The increased atRA concentrations in serum
      without a change in liver suggest that CYP26B1 in extrahepatic sites plays a key
      role in regulating systemic atRA exposure.

PMID- 28446508
TI  - Enrichment of PI3K-AKT-mTOR Pathway Activation in Hepatic Metastases from Breast
      Cancer.
AB  - Purpose: Little is known about the molecular signatures associated with specific
      metastatic sites in breast cancer. Using comprehensive multi-omic molecular
      profiling, we assessed whether alterations or activation of the PI3K-AKT-mTOR
      pathway is associated with specific sites of breast cancer
      metastasis.Experimental Design: Next-generation sequencing-based whole-exome
      sequencing was coupled with reverse-phase protein microarray (RPPA) functional
      signaling network analysis to explore the PI3K-AKT-mTOR axis in 32 pretreated
      breast cancer metastases. RPPA-based signaling data were further validated in an
      independent cohort of 154 metastatic lesions from breast cancer and 101 unmatched
      primary breast tumors. The proportion of cases with PI3K-AKT-mTOR genomic
      alterations or signaling network activation were compared between hepatic and
      nonhepatic lesions.Results:PIK3CA mutation and activation of AKT (S473) and
      p70S6K (T389) were detected more frequently among liver metastases than
      nonhepatic lesions (P < 0.01, P = 0.056, and P = 0.053, respectively). However,
      PIK3CA mutations alone were insufficient in predicting protein activation (P =
      0.32 and P = 0.19 for activated AKT and p70S6K, respectively). RPPA analysis of
      an independent cohort of 154 tumors confirmed the relationship between pathway
      activation and hepatic metastasis [AKT (S473), mTOR (S2448), and 4EBP1 (S65); P <
      0.01, P = 0.02, and P = 0.01, respectively]. Similar results were also seen
      between liver metastases and primary breast tumors [AKT (S473) P < 0.01, mTOR
      (S2448) P < 0.01, 4EBP1 (S65) P = 0.01]. This signature was lost when primary
      tumors were compared with all metastatic sites combined.Conclusions: Breast
      cancer patients with liver metastasis may represent a molecularly homogenized
      cohort with increased incidence of PIK3CA mutations and activation of the PI3K
      AKT-mTOR signaling network. Clin Cancer Res; 23(16); 4919-28. (c)2017 AACR.

PMID- 28446511
TI  - Learning to swim: role of gender, age and practice in Latino children, ages 3-14.
AB  - OBJECTIVE: We evaluate the effectiveness of a swim skill acquisition intervention
      among Latino youths, ages 3-14, a minority population at increased risk of
      drowning. METHODS: Parents were recruited through community institutions to have
      their children participate in group swim lessons. Each child's swim ability was
      assessed at baseline, and they were then exposed to swim lessons over an 8-week
      period, taught by trained professionals. The swim skill curriculum focused on
      water safety, flotation and endurance, at five levels of increasing skill
      acquisition. Final swim ability was assessed on the last day of the child's
      participation. Programme effectiveness was measured using direct pre-post
      comparisons with and without adjustment for key moderators (age and gender) and a
      mediator (number of practices). We also present a bias-adjusted estimate
      comparing low with high practice volume relying on a propensity score analysis.
      RESULTS: Among the 149 participating children, average acquisition was 12.3 swim
      skills (95% CI 10.7 to 14.1). Skill acquisition varied by age category (3-5, 6-9
      and 10-14 years) and by gender. We found a strong practice intensity effect, with
      skill acquisition accelerated for those participating in 10 or more swimming
      lessons. The propensity-adjusted estimate of the impact of 10 or more compared
      with 9 or fewer lessons was 8.2 skills (95% CI 4.8 to 11.8). CONCLUSIONS: An 8
      week swim intervention is effective at building skills in a community-based
      sample of Latino children, ages 3-14 years. The number of swimming lessons was a
      far stronger correlate of skill acquisition than were age or gender.

PMID- 28446510
TI  - A postprandial FGF19-SHP-LSD1 regulatory axis mediates epigenetic repression of
      hepatic autophagy.
AB  - Lysosome-mediated autophagy is essential for cellular survival and homeostasis
      upon nutrient deprivation, but is repressed after feeding. Despite the emerging
      importance of transcriptional regulation of autophagy by nutrient-sensing
      factors, the role for epigenetic control is largely unexplored. Here, we show
      that Small Heterodimer Partner (SHP) mediates postprandial epigenetic repression
      of hepatic autophagy by recruiting histone demethylase LSD1 in response to a late
      fed-state hormone, FGF19 (hFGF19, mFGF15). FGF19 treatment or feeding inhibits
      macroautophagy, including lipophagy, but these effects are blunted in SHP-null
      mice or LSD1-depleted mice. In addition, feeding-mediated autophagy inhibition is
      attenuated in FGF15-null mice. Upon FGF19 treatment or feeding, SHP recruits LSD1
      to CREB-bound autophagy genes, including Tfeb, resulting in dissociation of
      CRTC2, LSD1-mediated demethylation of gene-activation histone marks H3K4-me2/3,
      and subsequent accumulation of repressive histone modifications. Both FXR and SHP
      inhibit hepatic autophagy interdependently, but while FXR acts early, SHP acts
      relatively late after feeding, which effectively sustains postprandial inhibition
      of autophagy. This study demonstrates that the FGF19-SHP-LSD1 axis maintains
      homeostasis by suppressing unnecessary autophagic breakdown of cellular
      components, including lipids, under nutrient-rich postprandial conditions.

PMID- 28446512
TI  - Molecular mechanisms facilitating the initial kinetochore encounter with spindle
      microtubules.
AB  - The initial kinetochore (KT) encounter with a spindle microtubule (MT; KT
      capture) is one of the rate-limiting steps in establishing proper KT-MT
      interaction during mitosis. KT capture is facilitated by multiple factors, such
      as MT extension in various directions, KT diffusion, and MT pivoting. In
      addition, KTs generate short MTs, which subsequently interact with a spindle MT.
      KT-derived MTs may facilitate KT capture, but their contribution is elusive. In
      this study, we find that Stu1 recruits Stu2 to budding yeast KTs, which promotes
      MT generation there. By removing Stu2 specifically from KTs, we show that KT
      derived MTs shorten the half-life of noncaptured KTs from 48-49 s to 28-34 s.
      Using computational simulation, we found that multiple factors facilitate KT
      capture redundantly or synergistically. In particular, KT-derived MTs play
      important roles both by making a significant contribution on their own and by
      synergistically enhancing the effects of KT diffusion and MT pivoting. Our study
      reveals fundamental mechanisms facilitating the initial KT encounter with spindle
      MTs.

PMID- 28446513
TI  - Frequent hypomorphic alleles account for a significant fraction of ABCA4 disease
      and distinguish it from age-related macular degeneration.
AB  - BACKGROUND: Variation in the ABCA4 gene is causal for, or associated with, a wide
      range of phenotypes from early onset Mendelian retinal dystrophies to late-onset
      complex disorders such as age-related macular degeneration (AMD). Despite
      substantial progress in determining the causal genetic variation, even complete
      sequencing of the entire open reading frame and splice sites of ABCA4 identifies
      biallelic mutations in only 60%-70% of cases; 20%-25% remain with one mutation
      and no mutations are found in 10%-15% of cases with clinically confirmed ABCA4
      disease. This study was designed to identify missing causal variants specifically
      in monoallelic cases of ABCA4 disease. METHODS: Direct sequencing and analysis
      were performed in a large familial ABCA4 disease cohort of predominately European
      descent (n=643). Patient phenotypes were assessed from clinical and retinal
      imaging data. RESULTS: We determined that a hypomorphic ABCA4 variant c.5603A>T
      (p.Asn1868Ile), previously considered benign due to high minor allele frequency
      (MAF) (~7%) in the general population, accounts for 10% of the disease, >50% of
      the missing causal alleles in monoallelic cases, ~80% of late-onset cases and
      distinguishes ABCA4 disease from AMD. It results in a distinct clinical phenotype
      characterised by late-onset of symptoms (4th decade) and foveal sparing (85%).
      Intragenic modifying effects involving this variant and another, c.2588G>C
      (p.Gly863Ala) allele, were also identified. CONCLUSIONS: These findings
      substantiate the causality of frequent missense variants and their phenotypic
      outcomes as a significant contribution to ABCA4 disease, particularly the late
      onset phenotype, and its clinical variation. They also suggest a significant
      revision of diagnostic screening and assessment of ABCA4 variation in aetiology
      of retinal diseases.

PMID- 28446514
TI  - Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal
      study.
AB  - OBJECTIVE: Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal
      recessive disorder characterized by progressive organ-specific autoimmunity.
      There is scant information on APS1 in ethnic groups other than European
      Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene
      mutations in a cohort of Indian APS1 patients. DESIGN: Twenty-three patients (19
      families) from six referral centres in India, diagnosed between 1996 and 2016,
      were followed for [median (range)] 4 (0.2-19) years. METHODS: Clinical features,
      mortality, organ-specific autoantibodies and AIRE gene mutations were studied.
      RESULTS: Patients varied widely in their age of presentation [3.5 (0.1-17) years]
      and number of clinical manifestations [5 (2-11)]. Despite genetic heterogeneity,
      the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%;
      hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to
      reports in European series. In contrast, primary hypothyroidism (23%) occurred
      more frequently and at an early age, while kerato-conjunctivitis, urticarial rash
      and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a
      young age [5.8 (3-23) years] due to septicaemia, hepatic failure and
      adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon
      alpha and/or interleukin-22 antibodies were elevated in all 19 patients tested,
      including an asymptomatic infant. Eleven AIRE mutations were detected, the most
      common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel,
      while six others were previously described in European Caucasians. CONCLUSIONS:
      Indian APS1 patients exhibited considerable genetic heterogeneity and had highly
      variable clinical features. While the frequency of major manifestations was
      similar to that of European Caucasians, other features showed significant
      differences. A high mortality at a young age was observed.

PMID- 28446515
TI  - Role of Biomarkers for the Prevention, Assessment, and Management of Heart
      Failure: A Scientific Statement From the American Heart Association.
AB  - BACKGROUND AND PURPOSE: Natriuretic peptides have led the way as a diagnostic and
      prognostic tool for the diagnosis and management of heart failure (HF). More
      recent evidence suggests that natriuretic peptides along with the next generation
      of biomarkers may provide added value to medical management, which could
      potentially lower risk of mortality and readmissions. The purpose of this
      scientific statement is to summarize the existing literature and to provide
      guidance for the utility of currently available biomarkers. METHODS: The writing
      group used systematic literature reviews, published translational and clinical
      studies, clinical practice guidelines, and expert opinion/statements to summarize
      existing evidence and to identify areas of inadequacy requiring future research.
      The panel reviewed the most relevant adult medical literature excluding routine
      laboratory tests using MEDLINE, EMBASE, and Web of Science through December 2016.
      The document is organized and classified according to the American Heart
      Association to provide specific suggestions, considerations, or contemporary
      clinical practice recommendations. RESULTS: A number of biomarkers associated
      with HF are well recognized, and measuring their concentrations in circulation
      can be a convenient and noninvasive approach to provide important information
      about disease severity and helps in the detection, diagnosis, prognosis, and
      management of HF. These include natriuretic peptides, soluble suppressor of
      tumorgenicity 2, highly sensitive troponin, galectin-3, midregional
      proadrenomedullin, cystatin-C, interleukin-6, procalcitonin, and others. There is
      a need to further evaluate existing and novel markers for guiding therapy and to
      summarize their data in a standardized format to improve communication among
      researchers and practitioners. CONCLUSIONS: HF is a complex syndrome involving
      diverse pathways and pathological processes that can manifest in circulation as
      biomarkers. A number of such biomarkers are now clinically available, and
      monitoring their concentrations in blood not only can provide the clinician
      information about the diagnosis and severity of HF but also can improve
      prognostication and treatment strategies.

PMID- 28446516
TI  - Access to Nonstatin Lipid-Lowering Therapies in Patients at High Risk of
      Atherosclerotic Cardiovascular Disease.

PMID- 28446517
TI  - A Novel alpha-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ
      Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure.
AB  - BACKGROUND: Research into the therapeutic potential of alpha-calcitonin gene
      related peptide (alpha-CGRP) has been limited because of its peptide nature and
      short half-life. Here, we evaluate whether a novel potent and long-lasting (t1/2
      >=7 hours) acylated alpha-CGRP analogue (alphaAnalogue) could alleviate and
      reverse cardiovascular disease in 2 distinct murine models of hypertension and
      heart failure in vivo. METHODS: The ability of the alphaAnalogue to act
      selectively via the CGRP pathway was shown in skin by using a CGRP receptor
      antagonist. The effect of the alphaAnalogue on angiotensin II-induced
      hypertension was investigated over 14 days. Blood pressure was measured by
      radiotelemetry. The ability of the alphaAnalogue to modulate heart failure was
      studied in an abdominal aortic constriction model of murine cardiac hypertrophy
      and heart failure over 5 weeks. Extensive ex vivo analysis was performed via RNA
      analysis, Western blot, and histology. RESULTS: The angiotensin II-induced
      hypertension was attenuated by cotreatment with the alphaAnalogue (50 nmol.kg-1.d
      1, SC, at a dose selected for lack of long-term hypotensive effects at baseline).
      The alphaAnalogue protected against vascular, renal, and cardiac dysfunction,
      characterized by reduced hypertrophy and biomarkers of fibrosis, remodeling,
      inflammation, and oxidative stress. In a separate study, the alphaAnalogue
      reversed angiotensin II-induced hypertension and associated vascular and cardiac
      damage. The alphaAnalogue was effective over 5 weeks in a murine model of cardiac
      hypertrophy and heart failure. It preserved heart function, assessed by
      echocardiography, while protecting against adverse cardiac remodeling and
      apoptosis. Moreover, treatment with the alphaAnalogue was well tolerated with
      neither signs of desensitization nor behavioral changes. CONCLUSIONS: These
      findings, in 2 distinct models, provide the first evidence for the therapeutic
      potential of a stabilized alphaAnalogue, by mediating (1) antihypertensive
      effects, (2) attenuating cardiac remodeling, and (3) increasing angiogenesis and
      cell survival to protect against and limit damage associated with the progression
      of cardiovascular diseases. This indicates the therapeutic potential of the CGRP
      pathway and the possibility that this injectable CGRP analogue may be effective
      in cardiac disease.

PMID- 28446518
TI  - Glutaminyl Cyclase Inhibitor PQ912 Improves Cognition in Mouse Models of
      Alzheimer's Disease-Studies on Relation to Effective Target Occupancy.
AB  - Numerous studies suggest that the majority of amyloid-beta (Abeta) peptides
      deposited in Alzheimer's disease (AD) are truncated and post-translationally
      modified at the N terminus. Among these modified species, pyroglutamyl-Abeta (pE
      Abeta, including N3pE-Abeta40/42 and N11pE-Abeta40/42) has been identified as
      particularly neurotoxic. The N-terminal modification renders the peptide
      hydrophobic, accelerates formation of oligomers, and reduces degradation by
      peptidases, leading ultimately to the accumulation of the peptide and progression
      of AD. It has been shown that the formation of pyroglutamyl residues is catalyzed
      by glutaminyl cyclase (QC). Here, we present data about the pharmacological in
      vitro and in vivo efficacy of the QC inhibitor (S)-1-(1H-benzo[d]imidazol-5-yl)-5
      (4-propoxyphenyl)imidazolidin-2-one (PQ912), the first-in-class compound that is
      in clinical development. PQ912 inhibits human, rat, and mouse QC activity, with
      Ki values ranging between 20 and 65 nM. Chronic oral treatment of hAPPSLxhQC
      double-transgenic mice with approximately 200 mg/kg/day via chow shows a
      significant reduction of pE-Abeta levels and concomitant improvement of spatial
      learning in a Morris water maze test paradigm. This dose results in a brain and
      cerebrospinal fluid concentration of PQ912 which relates to a QC target occupancy
      of about 60%. Thus, we conclude that >50% inhibition of QC activity in the brain
      leads to robust treatment effects. Secondary pharmacology experiments in mice
      indicate a fairly large potency difference for Abeta cyclization compared with
      cyclization of physiologic substrates, suggesting a robust therapeutic window in
      humans. This information constitutes an important translational guidance for
      predicting the therapeutic dose range in clinical studies with PQ912.

PMID- 28446520
TI  - Obituary: Tokindo S. Okada (1927-2017).
AB  - Hisato Kondoh and Harukazu Nakamura look back at the life and career of their
      mentor Tokindo S. Okada, a pioneer of Japanese developmental biology.

PMID- 28446519
TI  - Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and
      Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing
      Endotoxemia.
AB  - A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic
      fatty liver disease, and obesity, has imposed critical challenges for societies
      worldwide, prompting investigation of underlying mechanisms and exploration of
      low-cost and effective treatment. In this report, we demonstrate that metabolic
      disorders in mice generated by feeding with a high-fat diet without dietary
      vitamin D can be prevented by oral administration of polycationic amine resin.
      Oral administration of cholestyramine, but not the control uncharged polystyrene,
      was able to sequester negatively charged bacterial endotoxin in the gut, leading
      to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and
      hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis,
      characterized as an increase of the phylum Firmicutes and a decrease of
      Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine,
      indicating that the negatively charged components in the gut are critical for the
      dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine
      treated animals, was sufficient to antagonize the metabolic disorders of the
      recipient mice. These results indicate that the negatively charged components
      produced by dysbiosis are critical for biogenesis of metabolic disorders and also
      show a potential application of cationic polystyrene to treat metabolic disorders
      through promoting gut eubiosis.

PMID- 28446521
TI  - Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in STEMI and
      NSTEMI Patients (PINPOINT): protocol for a prospective, observational, single
      centre study.
AB  - INTRODUCTION: The most common classification of acute myocardial infarction (AMI)
      is based on electrocardiographic findings and distinguishes ST-elevation
      myocardial infarction (STEMI) and non-ST-elevation myocardial infarction
      (NSTEMI). Both types of AMI differ concerning their epidemiology, clinical
      approach and early outcomes. Ticagrelor is a P2Y12 receptor inhibitor,
      constituting the first-line treatment for STEMI and NSTEMI. According to
      available data, STEMI may be associated with lower plasma concentration of
      ticagrelor in the first hours of AMI, but currently there are no studies directly
      comparing ticagrelor pharmacokinetics or antiplatelet effect in patients with
      STEMI versus NSTEMI. METHODS AND ANALYSIS: The PINPOINT study is a phase IV,
      single-centre, investigator-initiated, prospective, observational study designed
      to compare the pharmacokinetics and pharmacodynamics of ticagrelor in patients
      with STEMI and NSTEMI assigned to the invasive strategy of treatment. Based on an
      internal pilot study, the trial is expected to include at least 23 patients with
      each AMI type. All subjects will receive a 180 mg loading dose of ticagrelor. The
      primary end point of the study is the area under the plasma concentration-time
      curve (AUC(0-6)) for ticagrelor during the first 6 hours after the loading dose.
      Secondary end points include various pharmacokinetic features of ticagrelor and
      its active metabolite (AR-C124910XX), and evaluation of platelet reactivity by
      the vasodilator-stimulated phosphoprotein assay and multiple electrode
      aggregometry. Blood samples for the pharmacokinetic and pharmacodynamic
      assessment will be obtained at pretreatment, 30 min, 1, 2, 3, 4, 6 and 12 hours
      post-ticagrelor loading dose. ETHICS AND DISSEMINATION: The study received
      approval from the Local Ethics Committee (Komisja Bioetyczna Uniwersytetu
      Mikolaja Kopernika w Toruniu przy Collegium Medicum im. Ludwika Rydygiera w
      Bydgoszczy; approval reference number KB 617/2015). The study results will be
      disseminated through conference presentations and peer-reviewed journals. TRIAL
      REGISTRATION NUMBER: NCT02602444; Pre-results.

PMID- 28446523
TI  - Evaluation of the COPING parent online universal programme: study protocol for a
      pilot randomised controlled trial.
AB  - TRIAL SPONSOR: Bangor University, Brigantia Building, College Road, Bangor, LL57
      2AS, UK INTRODUCTION: The COPING parent online universal programme is a web-based
      parenting intervention for parents of children aged 3-8 years with an interest in
      positive parenting. The programme focuses on strengthening parent-child
      relationships and encouraging positive child behaviour. This trial will evaluate
      whether the intervention is effective in increasing the use of positive parenting
      strategies outlined in the programme using parent report and blind observation
      measures. METHODS AND ANALYSIS: This is a pilot randomised controlled trial with
      intervention and wait-list control conditions. The intervention is a 10-week
      online parenting programme to promote positive parent-child relations by teaching
      core social learning theory principles that encourage positive child behaviour,
      primarily through the use of praise and rewards. Health visitors and school
      nurses will circulate a recruitment poster to parents of children aged 3-8 years
      on their current caseloads. Recruitment posters will also be distributed via
      local primary schools and nurseries. Parents recruited to the trial will be
      randomised on a 2:1 ratio to intervention or wait-list control conditions
      (stratified according to child gender and age). The primary outcome measure is
      positive parenting as measured by a behavioural observation of parent-child
      interactions using the Dyadic Parent-Child Interaction Coding System. Secondary
      outcomes include parent report of child behaviour, and self-reported parental
      sense of competence, parenting behaviour and parental mental health. Data will be
      collected at baseline and 3 months later (postintervention) for all participants
      and 6 months postbaseline for the intervention group only. Analysis of covariance
      will be the main statistical method used. ETHICS AND DISSEMINATION: The trial has
      received ethical approval from the NHS Betsi Cadwaladr University Health Board
      Ethics Committee (REC) and the School of Psychology, Bangor University REC
      (15/WA/0463). Publication of all outcomes will be in peer-reviewed journals and
      conference presentations. TRIAL REGISTRATION NUMBER: Current Controlled Trials
      ISRCTN89370147 (5 May 2016).

PMID- 28446522
TI  - Improving opioid safety practices in primary care: protocol for the development
      and evaluation of a multifaceted, theory-informed pilot intervention for
      healthcare providers.
AB  - INTRODUCTION: In North America, drug overdose deaths are reaching unprecedented
      levels, largely driven by increasing prescription opioid-related deaths. Despite
      the development of several opioid guidelines, prescribing behaviours still
      contribute to poor patient outcomes and societal harm. Factors at the provider
      and system level may hinder or facilitate the application of evidence-based
      guidelines; interventions designed to address such factors are needed. METHODS
      AND ANALYSIS: Using implementation science and behaviour change theory, we have
      planned the development and evaluation of a comprehensive Opioid Self-Assessment
      Package, designed to increase adherence to the Canadian Opioid Guideline among
      family physicians. The intervention uses practical educational and self
      assessment tools to provide prescribers with feedback on their current knowledge
      and practices, and resources to improve their practice. The evaluation approach
      uses a pretest and post-test design and includes both quantitative and
      qualitative methods at baseline and 6 months. We will recruit a purposive sample
      of approximately 10 family physicians in Ontario from diverse practice settings,
      who currently treat patients with long-term opioid therapy for chronic pain.
      Quantitative data will be analysed using basic descriptive statistics, and
      qualitative data will be analysed using the Framework Method. ETHICS AND
      DISSEMINATION: The University Health Network Research Ethics Board approved this
      study. Dissemination plan includes publications, conference presentations and
      brief stakeholder reports. This evidence-informed, theory-driven intervention has
      implications for national application of opioid quality improvement tools in
      primary care settings. We are engaging experts and end users in advisory and
      stakeholder roles throughout our project to increase its national relevance,
      application and sustainability. The performance measures could be used as the
      basis for health system quality improvement indicators to monitor opioid
      prescribing. Additionally, the methods and approach used in this study could be
      adapted for other opioid guidelines, or applied to other areas of preventive
      healthcare and clinical guideline implementation processes.

PMID- 28446524
TI  - Experiences, attitudes and possibilities for improvement concerning the
      cooperation between occupational physicians, rehabilitation physicians and
      general practitioners in Germany from the perspectives of the medical groups and
      rehabilitation patients - a protocol for a qualitative study.
AB  - INTRODUCTION: Rehabilitation measures for patients in the working age primarily
      aim at maintaining employability, restoring fitness for work or timely return to
      work (RTW). To facilitate RTW after long sick leave in Germany, both
      rehabilitation physicians' knowledge about the patients' workplace and
      communication between the rehabilitation physician and the occupational physician
      need to be improved. This research will record the experiences and attitudes of
      occupational physicians, rehabilitation physicians and general practitioners, as
      well as of rehabilitation patients, to indicate barriers and possibilities for
      improvement concerning the intersection between workplace and rehabilitation
      institution. As a previous literature review has shown, insufficient data on the
      experiences and attitudes of the stakeholders are available. Therefore, an
      exploratory qualitative approach was chosen. METHODS AND ANALYSIS: 8 focus group
      discussions will be conducted with occupational physicians, rehabilitation
      physicians, general practitioners and rehabilitation patients (2 focus groups
      with 6-8 interviewees per category). Qualitative content analysis will be used to
      evaluate the data, thus describing positive and negative experiences and
      attitudes, barriers and possibilities for improvement at the intersection of
      general and occupational medicine and rehabilitation with regard to the
      workplace. The data from the focus groups will be used to develop a standardised
      quantitative questionnaire for a survey of the medical groups and rehabilitation
      patients in a follow-up project. ETHICS AND DISSEMINATION: The research will be
      undertaken with the approval of the Ethics Committee of the Medical Faculty and
      University Hospital of Tuebingen. The study participants' consent will be
      documented in written form. The names of all study participants and all other
      confidential information data fall under medical confidentiality. The results
      will be published in a peer-reviewed medical journal independent of the nature of
      the results.

PMID- 28446525
TI  - Effectiveness of befriending interventions: a systematic review and meta
      analysis.
AB  - OBJECTIVE: Befriending is an emotional supportive relationship in which one-to
      one companionship is provided on a regular basis by a volunteer. It is commonly
      and increasingly offered by the voluntary sector for individuals with distressing
      physical and mental conditions. However, the effectiveness of this intervention
      on health outcomes is largely unknown. We aim to conduct a systematic review of
      the benefits of befriending. DESIGN: Systematic review. METHODS: A systematic
      search of electronic databases was conducted to identify randomised controlled
      trials and quasi-experimental trials of befriending for a range of physical and
      mental health indications including depression, anxiety, mental illness, cancer,
      physical illness and dementia. Main outcomes included patient-relevant and
      disease-specific outcomes, such as depression, loneliness, quality of life, self
      esteem, social support and well-being. RESULTS: A total of 14 trials (2411
      participants) were included; 7 were judged at low risk of bias. Most trials
      showed improvement in symptoms associated with befriending but these associations
      did not reach statistical significance in all trials. Befriending was
      significantly associated with better patient-reported outcomes across primary
      measures (standardised mean difference 0.18 (95% CI, -0.002 to 0.36, I2=26%,
      seven trials)). However, there was no significant benefit on single outcomes,
      including depression, quality of life, loneliness ratings, self-esteem measures,
      social support structures and well-being. CONCLUSIONS: There was moderate quality
      evidence to support the use of befriending for the treatment of individuals with
      different physical and mental health conditions. This evidence refers to an
      overall improvement benefit in patient-reported primary outcomes, although with a
      rather small effect size. The current evidence base does not allow for firm
      conclusions on more specific outcomes. Future trials should hypothesise a model
      for the precise effects of befriending and use specified inclusion and outcome
      criteria.

PMID- 28446526
TI  - Impact of different dietary approaches on blood pressure in hypertensive and
      prehypertensive patients: protocol for a systematic review and network meta
      analysis.
AB  - INTRODUCTION: Lifestyle modification is one of the cornerstones in the management
      of hypertension. According to the most recent guidelines by the American Heart
      Association, all patients with hypertension should adopt the following dietary
      advices: increased consumption of fresh fruits, vegetables, low-fat dairy
      products and sodium reduction. The aim of the present study is to assess the
      efficacy of different dietary approaches on systolic and diastolic blood pressure
      in patients with hypertension and high normal blood pressure in a systematic
      review including a pairwise and network meta-analysis of randomised trials.
      METHODS AND ANALYSIS: We conducted searches in Cochrane Central Register of
      Controlled Trials in the Cochrane Library, PubMed and Google Scholar until
      November 2016. Citations, abstracts and relevant papers were screened for
      eligibility by two reviewers independently. Randomised trials were included if
      they met the following criteria: (1) hypertension (as mean values >=140 mm Hg
      systolic blood pressure and/or >=90 mm Hg diastolic blood pressure) or high
      normal blood pressure (mean systolic blood pressure >=130 mm Hg and/or mean
      diastolic blood pressure >=85 mm Hg), (2) age >=18 years, (3) intervention diets
      (different type of dietary approaches, eg, dietary approach to stop hypertension
      diet; Mediterranean diet, vegetarian diet, palaeolithic diet, low sodium diet)
      either hypocaloric, isocaloric or ad libitum diets, (4) intervention period >=12
      weeks. For each outcome measure of interest, random effects pairwise and network
      meta-analyses were performed in order to determine the pooled relative effect of
      each intervention relative to every other intervention in terms of the
      postintervention values (or change scores). Subgroup analyses were planned for
      hypertensive status, study length, sample size, age and sex. ETHICS AND
      DISSEMINATION: As this study is based solely on the published literature, no
      ethics approval was required. We published our network meta-analysis in a peer
      reviewed scientific journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO:
      CRD42016049243.

PMID- 28446527
TI  - The value of different aspects of person-centred care: a series of discrete
      choice experiments in people with long-term conditions.
AB  - OBJECTIVE: To measure the value the patients place on different aspects of person
      centred care. DESIGN: We systematically identified four attributes of person
      centred care. We then measured their value to 923 people with either chronic pain
      or chronic lung disease over three discrete choice experiments (DCEs) about
      services to support self-management. We calculated the value of each attribute
      for all respondents and identified groups of people with similar preferences
      using latent class modelling. SETTING: DCEs conducted online via a commercial
      survey company. PARTICIPANTS: Adults with either chronic pain (two DCEs, n=517
      and 206, respectively) or breathlessness due to chronic respiratory disease
      (n=200). RESULTS: Participants were more likely to choose services with higher
      level person-centred attributes. They most valued services that took account of a
      person's current situation likelihood of selection increased by 16.9% (95%
      CI=15.4 to 18.3) and worked with the person on what they wanted to get from life
      (15.8%; 14.5 to 17.1). More personally relevant information was valued less than
      these (12.3%; 11.0 to 13.6). A friendly and personal communicative style was
      valued least (3.8%; 2.7 to 4.8). Latent class models indicated that a substantial
      minority of participants valued personally relevant information over the other
      attributes. CONCLUSION: This is the first study to measure the value patients
      place on different aspects of person-centred care. Professional training needs to
      emphasise the substance of clinical communication-working responsively with
      individuals on what matters to them-as well as the style of its delivery.

PMID- 28446528
TI  - Quitting patient care and career break intentions among general practitioners in
      South West England: findings of a census survey of general practitioners.
AB  - OBJECTIVE: Given recent concerns regarding general practitioner (GP) workforce
      capacity, we aimed to describe GPs' career intentions, especially those which
      might impact on GP workforce availability over the next 5 years. DESIGN: Census
      survey, conducted between April and June 2016 using postal and online responses ,
      of all GPs on the National Health Service performers list and eligible to
      practise in primary care. Two reminders were used as necessary. SETTING: South
      West England (population 3.5  million), a region with low overall socioeconomic
      deprivation. PARTICIPANTS: Eligible GPs were 2248 out of 3370 (67 % response
      rate). MAIN OUTCOME MEASURES: Reported likelihood of permanently leaving or
      reducing hours spent in direct patient care or of taking a career break within
      the next 5 years and present morale weighted for non-response. RESULTS:
      Responders included 217 7 GPs engaged in patient care. Of these, 863 (37%
      weighted, 95%  CI 35 % to 39 %) reported a high likelihood of quitting direct
      patient care within the next 5 years. Overall, 1535 (70% weighted, 95%  CI 68 %
      to 72 %) respondents reported a career intention that would negatively impact GP
      workforce capacity over the next 5 years, through permanently leaving or reducing
      hours spent in direct patient care, or through taking a career break. GP age was
      an important predictor of career intentions; sharp increases in the proportion of
      GPs intending to quit patient care were evident from 52 years. Only 305 (14%
      weighted, 95%  CI 13 % to 16 %) reported high morale, while 1195 ( 54 % weighted,
      95%  CI 52 % to 56 %) reported low morale. Low morale was particularly common
      among GP partners. Current morale strongly predicted GPs' career intentions;
      those with very low morale were particularly likely to report intentions to quit
      patient care or to take a career break. CONCLUSIONS: A substantial majority of
      GPs in South West England report low morale. Many are considering career
      intentions which, if implemented, would adversely impact GP workforce capacity
      within a short time period. STUDY REGISTRATION: NIHR HS&DR - 14/196/02, UKCRN ID
      20700.

PMID- 28446529
TI  - Strengths, Risk Factors, and Resilient Outcomes in Adolescents With Type 1
      Diabetes: Results From Diabetes MILES Youth-Australia.
AB  - OBJECTIVE: Despite the challenges of living with type 1 diabetes, many
      adolescents achieve "resilient outcomes": high engagement in self-management
      behaviors such as self-monitoring of blood glucose (SMBG), good quality of life
      (QOL), and within-target glycemic outcomes (HbA1c). Adaptive diabetes-related
      behaviors (i.e., "strengths") are associated with resilient outcomes, yet the
      combination of risks and strengths in relation to resilient outcomes is unclear.
      The aim of this study was to investigate relations among diabetes strengths and
      resilient outcomes in the context of psychological and family risk factors.
      RESEARCH DESIGN AND METHODS: A total of 471 Australian adolescents with type 1
      diabetes (mean age 15.7 +/- 1.9 years; diabetes duration 6.9 +/- 4.2 years; 62%
      female; 53% using insulin pumps) completed a national cross-sectional survey
      about their diabetes-related strengths, risk factors (depressive/anxiety
      symptoms, family conflict), and resilient outcomes (SMBG frequency, general QOL,
      HbA1c). RESULTS: Greater diabetes strengths were significantly related to
      resilient outcomes: more frequent SMBG (r = 0.39), lower HbA1c (r = -0.31), and
      higher general QOL (r = 0.50), as well as to lower risks: fewer depressive (r = 
      0.45) and anxiety (r = -0.40) symptoms and less conflict (r = 0.28). In
      multivariate regressions, diabetes strengths consistently related to all
      resilient outcomes beyond significant risk factors. CONCLUSIONS: In a large
      sample of Australian adolescents, diabetes strengths were strongly related to key
      resilient outcomes, even in the presence of well-documented psychological and
      family risk factors. More research is needed to determine whether strengths
      reduce or buffer other risks. Given the associations with self-management, HbA1c,
      and general QOL, monitoring and enhancing diabetes strengths may support
      resilience promotion during a vulnerable developmental period.

PMID- 28446531
TI  - Mining Exosomal Genes for Pancreatic Cancer Targets.
AB  - BACKGROUND: Exosomes, cell-derived vesicles encompassing lipids, DNA, proteins
      coding genes and noncoding RNAs (ncRNAs) are present in diverse body fluids. They
      offer novel biomarker and drug therapy potential for diverse diseases, including
      cancer. MATERIALS AND METHODS: Using gene ontology, exosomal genes database and
      GeneCards metadata analysis tools, a database of cancer-associated protein coding
      genes and ncRNAs (n=2,777) was established. Variant analysis, expression
      profiling and pathway mapping were used to identify putative pancreatic cancer
      exosomal gene candidates. RESULTS: Five hundred and seventy-five protein-coding
      genes, 26 RNA genes and one pseudogene directly associated with pancreatic cancer
      were identified in the study. Nine open reading frames (ORFs) encompassing
      enzymes, apoptosis and transcriptional regulators, and secreted factors and five
      cDNAs (enzymes) emerged from the analysis. Among the ncRNA class, 26 microRNAs
      (miRs), one pseudogene, one long noncoding RNA (LNC) and one antisense gene were
      identified. Furthermore, 22 exosome-associated protein-coding targets (a
      cytokine, enzymes, membrane glycoproteins, receptors, and a transporter) emerged
      as putative leads for pancreatic cancer therapy. Seven of these protein-coding
      targets are FDA-approved and the drugs-based on these could provide repurposing
      opportunities for pancreatic cancer. CONCLUSION: The database of exosomal genes
      established in this study provides a framework for developing novel biomarkers
      and drug therapy targets for pancreatic cancer.

PMID- 28446530
TI  - Long Non-coding RNAs and their Role in Metastasis.
AB  - The perception of long non-coding RNAs as chunk RNA and transcriptional noise has
      been steadily replaced by their role as validated targets for a diverse set of
      physiological processes in the past few years. However, for the vast majority of
      lncRNAs their precise mode of action and physiological function remain to be
      uncovered. A large body of evidence has revealed their essential role in all
      stages of cancirogenesis and metastasis. In this review we focus on the role of
      lncRNAs in metastasis. We grouped selected lncRNAs into three categories based on
      in vitro and in vivo mode of action-related studies and clinical relevance for
      metastasis. Grouped according to their mode of action, in category I we discuss
      lncRNAs such as CCAT2, DREH, LET, NKILA, treRNA, HOTAIR, H19, FENDRR, lincROR,
      MALAT, GClnc1, BCAR4, SCHLAP1 and lncRNA ATP, all lncRNAs with in vitro and in
      vivo metastasis-related data and clinical significance. In category II we discuss
      lncRNAs CCAT1, PCAT1, PTENgp1, GPLINC, MEG3, ZEB2-AS, LCT13, ANRIL, NBAT1 and
      lncTCF7 all characterized by their mode of action in vitro and clinical
      significance, but pending or preliminary in vivo data. Finally, under category
      III, we discuss lncRNAs BANCR, FRLnc1, SPRY4-IT1 and LIMT with partially or
      poorly-resolved mode of action and varying degree of validation in clinical
      metastasis. Finally we discuss metastasis-related translational aspects of
      lncRNAs.

PMID- 28446532
TI  - Next-generation Sequencing (NGS) Analysis on Single Circulating Tumor Cells
      (CTCs) with No Need of Whole-genome Amplification (WGA).
AB  - BACKGROUND: Isolation and genotyping of circulating tumor cells (CTCs) is gaining
      an increasing interest by clinical researchers in oncology not only for
      investigative purposes, but also for concrete application in clinical practice in
      terms of diagnosis, prognosis and decision treatment with targeted therapies. For
      the mutational analysis of single CTCs, the most advanced biotechnology
      methodology currently available includes the combination of whole genome
      amplification (WGA) followed by next-generation sequencing (NGS). However, the
      sequence of these molecular techniques is time-consuming and may also favor
      operator-dependent errors, related to the procedures themselves that, as in the
      case of the WGA technique, might affect downstream molecular analyses. MATERIALS
      AND METHODS: A preliminary approach of molecular analysis by NGS on a model of
      CTCs without previous WGA procedural step was performed. We set-up an artificial
      sample obtained by spiking the SK-MEL-28 melanoma cell line in normal donor
      peripheral whole blood. Melanoma cells were first enriched using an AutoMACS(r)
      (Miltenyi) cell separator and then isolated as single and pooled CTCs by
      DEPArrayTM System (Silicon Biosystems). NGS analysis, using the Ion AmpliSeqTM
      Cancer Hotspot Panel v2 (Life Technologies) with the Ion Torrent PGMTM system
      (Life Technologies), was performed on the SK-MEL-28 cell pellet, a single CTC
      previously processed with WGA and on 1, 2, 4 and 8 recovered CTCs without WGA pre
      amplification. RESULTS: NGS directly carried out on CTCs without WGA showed the
      same mutations identified in SK-MEL-28 cell line pellet, with a considerable
      efficiency and avoiding the errors induced by the WGA procedure. CONCLUSION: We
      identified a cost-effective, time-saving and reliable methodological approach
      that could improve the analytical accuracy of the liquid biopsy and appears
      promising in studying CTCs from cancer patients for both research and clinical
      purposes.

PMID- 28446534
TI  - Proteomics Analysis of Tissue Samples Reveals Changes in Mitochondrial Protein
      Levels in Parathyroid Hyperplasia over Adenoma.
AB  - BACKGROUND/AIM: To unveil the pathophysiology of primary hyperparathyroidism,
      molecular details of parathyroid hyperplasia and adenoma have to be revealed.
      Such details will provide the tools necessary for differentiation of these two
      look-alike diseases. Therefore, in the present study, a comparative proteomic
      study using postoperative tissue samples from the parathyroid adenoma and
      parathyroid hyperplasia patients was performed. MATERIALS AND METHODS: Protein
      extracts were prepared from tissue samples (n=8 per group). Protein pools were
      created for each group and subjected to DIGE and conventional 2DE. Following
      image analysis, spots representing the differentially regulated proteins were
      excised from the and used for identification via MALDI-TOF/TOF analysis. RESULTS:
      The identities of 40 differentially-expressed proteins were revealed. Fourteen of
      these proteins were over-expressed in the hyperplasia while 26 of them were over
      expressed in the adenoma. CONCLUSION: Most proteins found to be over-expressed in
      the hyperplasia samples were mitochondrial, underlying the importance of the
      mitochondrial activity as a potential biomarker for differentiation of
      parathyroid hyperplasia from adenoma.

PMID- 28446535
TI  - Direct transfer to angiosuite to reduce door-to-puncture time in thrombectomy for
      acute stroke.
AB  - OBJECTIVE: To evaluate direct transfer to the angiosuite protocol of patients
      with acute stroke, candidates for endovascular treatment (EVT). METHODS: We
      studied workflow metrics of all patients with stroke who had undergone EVT in the
      past 12 months. Patients followed three protocols: direct transfer to emergency
      room (DTER), CT room (DTCT) or angiosuite (DTAS, only last 6 months if admission
      National Institute of Health Stroke Scale (NIHSS) score >9 and time from onset
      <4.5 hours) according to staff/suite availability. DTAS patients underwent cone
      beam CT before femoral puncture. Dramatic clinical improvement was defined as 10
      NIHSS points drop at 24 hours. RESULTS: 201 patients were included: 87 DTER
      (43.3%), 74 DTCT (36.8%), 40 DTAS (19.9%).Ten DTAS patients (25%) did not receive
      EVT: 3 (7.5%) showed intracranial hemorrhage on cone-beam CT and 7 (17.5%) did
      not show an occlusion on angiography. Mean door-to-puncture (D2P) time was
      shorter in DTAS (17+/-8 min) than DTCT (60+/-29 min; p<0.01). D2P was longer in
      DTER (90+/-53 min) than in the other protocols (p<0.01). For outcome analyses
      only patients who received EVT were compared; no significant differences in
      baseline characteristics, including time from symptom-onset to admission,
      puncture-to-recanalization, or recanalization rate, were seen. However, time from
      symptom-to-puncture (DTAS: 197+/-72 min, DTER: 279+/-156, DTCT: 224+/-142 min;
      p=0.01) and symptom-to-recanalization (DTAS: 257+/-74, DTER: 355+/-158, DTCT:
      279+/-146 min; p<0.01) were longer in the DTER group. At 24 hours, there were no
      differences in NIHSS score (p=0.81); however, the rate of dramatic clinical
      improvement was significantly higher in DTAS: 48.6% (DTER 24.1%, DTCT 27.4%);
      p=0.01). An adjusted model pointed to shorter onset-to-puncture time as an
      independent predictor of dramatic improvement (OR=1.23, 95% CI 1.13 to 133;
      p<0.01) CONCLUSION: In a subgroup of patients direct transfer and triage in the
      angiosuite seems feasible, safe, and achieves significant reduction in hospital
      workflow times.

PMID- 28446533
TI  - Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and
      Phenotype Parameters in Triple-negative Breast Cancers.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) aberrations have been
      implicated in the pathogenesis of triple-negative breast cancer (TNBC) but their
      impact on prognosis and, therefore, druggability, remain controversial. Herein,
      we studied EGFR aberrations at different molecular levels and assessed their
      prognostic impact in patients with operable TNBC treated with adjuvant
      anthracycline-based chemotherapy. MATERIALS AND METHODS: We evaluated the
      prognostic impact of EGFR gene status by fluorescent in situ hybridization
      (FISH), EGFR coding mutations by Sanger and next-generation sequencing, relative
      EGFR messenger RNA (mRNA) levels by qPCR (upper quartile) and EGFR and p53
      protein expression by immunohistochemistry (IHC), in 352 centrally-assessed
      tumors from an equal number of TNBC patients. RESULTS: Approximately 53.5% of the
      tumors expressed EGFR, 59.3% p53 and 35.9% both EGFR and p53 proteins; 4.1%
      showed EGFR gene amplification and 4.4% carried EGFR mutations. The latter were
      located outside the druggable kinase domain region and presented at low
      frequencies. Amplification and mutations overlapped only in one case of glycogen
      rich carcinoma. EGFR and CEN7 copies were higher in tumors from older patients
      (p=0.002 and p=0.003, respectively). Patients with amplified tumors (n=11) had
      excellent prognosis (0 relapses and deaths). Upon multivariate analysis, high
      EGFR copies conferred significantly favorable disease-free survival (HR=0.57, 95%
      CI 0.36-0.90, Wald's p=0.017) and high CEN7 copies favorable overall survival
      (HR=0.49, 95% CI=0.29-0.83, Wald's p=0.008). Patients with EGFR-/p53+ and
      EGFR+/p53- tumors had significantly higher risk for relapse than those with EGFR
      /p53- and EGFR+/p53+ tumors (HR=1.73, 95% CI=1.12-2.67, Wald's p=0.013).
      CONCLUSION: EGFR gene amplification and mutations are rare in TNBC, the latter of
      no apparent clinical relevance. Surrogate markers of EGFR-related chromosomal
      aberrations and combined EGFR/p53 IHC phenotypes appear to be associated with
      favorable prognosis in patients with operable TNBC receiving conventional
      adjuvant chemotherapy.

PMID- 28446536
TI  - Donor-Specific Antibodies in Kidney Transplant Recipients.
AB  - Donor-specific antibodies have become an established biomarker predicting
      antibody-mediated rejection. Antibody-mediated rejection is the leading cause of
      graft loss after kidney transplant. There are several phenotypes of antibody
      mediated rejection along post-transplant course that are determined by the timing
      and extent of humoral response and the various characteristics of donor-specific
      antibodies, such as antigen classes, specificity, antibody strength, IgG
      subclasses, and complement binding capacity. Preformed donor-specific antibodies
      in sensitized patients can trigger hyperacute rejection, accelerated acute
      rejection, and early acute antibody-mediated rejection. De novo donor-specific
      antibodies are associated with late acute antibody-mediated rejection, chronic
      antibody-mediated rejection, and transplant glomerulopathy. The pathogeneses of
      antibody-mediated rejection include not only complement-dependent cytotoxicity,
      but also complement-independent pathways of antibody-mediated cellular
      cytotoxicity and direct endothelial activation and proliferation. The novel assay
      for complement binding capacity has improved our ability to predict antibody
      mediated rejection phenotypes. C1q binding donor-specific antibodies are closely
      associated with acute antibody-mediated rejection, more severe graft injuries,
      and early graft failure, whereas C1q nonbinding donor-specific antibodies
      correlate with subclinical or chronic antibody-mediated rejection and late graft
      loss. IgG subclasses have various abilities to activate complement and recruit
      effector cells through the Fc receptor. Complement binding IgG3 donor-specific
      antibodies are frequently associated with acute antibody-mediated rejection and
      severe graft injury, whereas noncomplement binding IgG4 donor-specific antibodies
      are more correlated with subclinical or chronic antibody-mediated rejection and
      transplant glomerulopathy. Our in-depth knowledge of complex characteristics of
      donor-specific antibodies can stratify the patient's immunologic risk, can
      predict distinct phenotypes of antibody-mediated rejection, and hopefully, will
      guide our clinical practice to improve the transplant outcomes.

PMID- 28446538
TI  - Chitosan nanoparticle-delivered siRNA reduces CXCR4 expression and sensitizes
      breast cancer cells to cisplatin.
AB  - Chemokine (C-X-C motif) receptor 4 (CXCR4) has been reported as a poor prognostic
      biomarker in human breast cancers, and has been suggested as a promising
      therapeutic target of breast cancer treatment. The present study aims to
      investigate the delivery efficiency of siRNA by chitosan into breast cancer
      cells, and then to examine the regulatory role by chitosan nanoparticle-delivered
      siRNA on CXCR4 expression and on the chemosensitivity of breast cancer cells. Our
      results demonstrated that the siRNA could be capsuled by chitosan into
      nanoparticles with a diameter of 80-110 nm, and with a zeta potential of 20-50
      mV. The chitosan nanoparticle delivered siRNA efficiently into breast cancer MCF
      7 cells significantly reduced the expression of CXCR4 in both mRNA and protein
      levels. Moreover, the reduced CXCR4 by chitosan nanoparticle-delivered siRNA was
      associated with increased sensitivity of breast cancer cells to cisplatin.
      Reduced growth and increased apoptosis of MCF-7 cells were observed in the CXCR4
      siRNA group than in the control siRNA group. Taken together, our results present
      the treatment potential of chitosan nanoparticle-delivered siRNA targeting CXCR4
      in breast cancers.

PMID- 28446537
TI  - Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel
      Added to Aspirin on Kidney Function.
AB  - BACKGROUND AND OBJECTIVES: Despite the high burden of CKD, few specific therapies
      are available that can halt disease progression. In animal models, clopidogrel
      has emerged as a potential therapy to preserve kidney function. The effect of
      clopidogrel on kidney function in humans has not been established. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: The Secondary Prevention of Small
      Subcortical Strokes Study randomized participants with prior lacunar stroke to
      treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR
      decline and incidence of rapid eGFR decline (>=30% from baseline) using
      generalized estimating equations and interval-censored proportional hazards
      regression, respectively. We also stratified our analyses by baseline eGFR,
      systolic BP target, and time after randomization. RESULTS: At randomization,
      median age was 62 (interquartile range, 55-71) years old; 36% had a history of
      diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range,
      65-94) ml/min per 1 m2. Persons receiving aspirin plus clopidogrel had an average
      annual change in kidney function of -1.39 (95% confidence interval, -1.15 to 
      1.62) ml/min per 1.73 m2 per year compared with -1.52 (95% confidence interval, 
      1.30 to -1.74) ml/min per 1.73 m2 per year among persons receiving aspirin only
      (P=0.42). Rapid kidney function decline occurred in 21% of participants receiving
      clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus
      placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P=0.42).
      Findings did not vary by baseline eGFR, time after randomization, or systolic BP
      target (all P values for interaction were >0.3). CONCLUSIONS: We found no effect
      of clopidogrel added to aspirin compared with aspirin alone on kidney function
      decline among persons with prior lacunar stroke.

PMID- 28446539
TI  - Transient mechanical strain promotes the maturation of invadopodia and enhances
      cancer cell invasion in vitro.
AB  - Cancer cell invasion is influenced by various biomechanical forces found within
      the microenvironment. We have previously found that invasion is enhanced in
      fibrosarcoma cells when transient mechanical stimulation is applied within an in
      vitro mechano-invasion assay. This enhancement of invasion is dependent on
      cofilin (CFL1), a known regulator of invadopodia maturation. Invadopodia are
      actin-rich structures present in invasive cancer cells that are enzymatically
      active and degrade the surrounding extracellular matrix to facilitate invasion.
      In this study, we examine changes in gene expression in response to tugging on
      matrix fibers. Interestingly, we find that integrin beta3 expression is
      downregulated and leads to an increase in cofilin activity, as evidenced by a
      reduction in its Ser3 phosphorylation levels. As a result, invadopodia lengthen
      and have increased enzymatic activity, indicating that transient mechanical
      stimulation promotes the maturation of invadopodia leading to increased levels of
      cell invasion. Our results are unique in defining an invasive mechanism specific
      to the invasive process of cancer cells that is triggered by tugging forces in
      the microenvironment, as opposed to rigidity, compression or stretch forces.

PMID- 28446540
TI  - Human prostate luminal cell differentiation requires NOTCH3 induction by p38-MAPK
      and MYC.
AB  - Many pathways dysregulated in prostate cancer are also involved in epithelial
      differentiation. To better understand prostate tumor initiation, we sought to
      investigate specific genes and mechanisms required for normal basal to luminal
      cell differentiation. Utilizing human prostate basal epithelial cells and an in
      vitro differentiation model, we tested the hypothesis that regulation of NOTCH3
      by the p38 MAPK family (hereafter p38-MAPK), via MYC, is required for luminal
      differentiation. Inhibition (SB202190 and BIRB796) or knockdown of p38alpha (also
      known as MAPK14) and/or p38delta (also known as MAPK13) prevented proper
      differentiation. Additionally, treatment with a gamma-secretase inhibitor
      (RO4929097) or knockdown of NOTCH1 and/or NOTCH3 greatly impaired differentiation
      and caused luminal cell death. Constitutive p38-MAPK activation through MKK6(CA)
      increased NOTCH3 (but not NOTCH1) mRNA and protein levels, which was diminished
      upon MYC inhibition (10058-F4 and JQ1) or knockdown. Furthermore, we validated
      two NOTCH3 enhancer elements through a combination of enhancer (e)RNA detection
      (BruUV-seq) and luciferase reporter assays. Finally, we found that the NOTCH3
      mRNA half-life increased during differentiation or upon acute p38-MAPK
      activation. These results reveal a new connection between p38-MAPK, MYC and NOTCH
      signaling, demonstrate two mechanisms of NOTCH3 regulation and provide evidence
      for NOTCH3 involvement in prostate luminal cell differentiation.

PMID- 28446541
TI  - Nuclear survivin expression correlates with endoglin-assessed
      microvascularisation in laryngeal carcinoma.
AB  - AIMS: Survivin-a member of the family of inhibitor of apoptosis proteins that
      control cell division, apoptosis and metastasis-is overexpressed in virtually all
      human cancers, including laryngeal squamous cell carcinoma (LSCC). Recent
      findings also correlate survivin expression with the regulation of angiogenesis.
      The novel main aim of this study was a preliminary investigation into the
      potential role of survivin expression in LSCC neoangiogenesis, as determined by
      endoglin-assessed microvascular density (MVD). METHODS: Immunohistochemical
      expression of nuclear survivin and endoglin-assessed MVD were ascertained by
      image analysis in 75 consecutive LSCCs. RESULTS: Statistical analysis disclosed a
      strong direct correlation between nuclear survivin expression and MVD. Patients
      whose nuclear survivin expression was >=6.0% had a significantly higher LSCC
      recurrence rate, and a significantly shorter disease-free survival (DFS) than
      those with a nuclear survivin expression <6.0%. The LSCC recurrence rate was also
      higher and the DFS shorter in patients with endoglin-assessed MVD >=6.89%. The OR
      for recurrence was 2.79 in patients with LSCC with a nuclear survivin expression
      >=6.0%, and 12.31 in those with an MVD>=6.89%. CONCLUSIONS: Survivin-targeting
      strategies to enhance tumour cell response to apoptosis and inhibit tumour growth
      should receive more attention with a view to developing agents for use in
      multimodality advanced LSCC treatment, or combined with conventional
      chemotherapy. Given the present preliminary evidence in LSCC, survivin targeting
      should also be further investigated for anti-angiogenic purposes, to reduce
      tumour blood flow and induce cancer necrosis.

PMID- 28446542
TI  - A Proteolytic Regulator Controlling Chalcone Synthase Stability and Flavonoid
      Biosynthesis in Arabidopsis.
AB  - Flavonoids represent a large family of specialized metabolites involved in plant
      growth, development, and adaptation. Chalcone synthase (CHS) catalyzes the first
      step of flavonoid biosynthesis by directing carbon flux from general
      phenylpropanoid metabolism to flavonoid pathway. Despite extensive
      characterization of its function and transcriptional regulation, the molecular
      basis governing its posttranslational modification is enigmatic. Here, we report
      the discovery of a proteolytic regulator of CHS, namely, KFBCHS, a Kelch domain
      containing F-box protein in Arabidopsis thaliana KFBCHS physically interacts with
      CHS and specifically mediates its ubiquitination and degradation. KFBCHS exhibits
      developmental expression patterns in Arabidopsis leaves, stems, and siliques and
      strongly responds to the dark-to-light (or the light-to-dark) switch, the blue,
      red, and far-red light signals, and UV-B irradiation. Alteration of KFBCHS
      expression negatively correlates to the cellular concentration of CHS and the
      production of flavonoids. Our study suggests that KFBCHS serves as a crucial
      negative regulator, via mediating CHS degradation, coordinately controlling
      flavonoid biosynthesis in response to the developmental cues and environmental
      stimuli.

PMID- 28446543
TI  - Comparison of the Natural History of Genital HPV Infection among Men by Country:
      Brazil, Mexico, and the United States.
AB  - Background: Male genital human papillomavirus (HPV) prevalence and incidence has
      been reported to vary by geographical location. Our objective was to assess the
      natural history of genital HPV by country among men with a median of 48 months of
      follow-up.Methods: Men ages 18-70 years were recruited from United States (n =
      1,326), Mexico (n = 1,349), and Brazil (n = 1,410). Genital specimens were
      collected every 6 months and HPV genotyping identified 37 HPV genotypes.
      Prevalence of HPV was compared between the three countries using the Fisher exact
      test. Incidence rates and 95% confidence intervals were calculated. The median
      time to HPV clearance among men with an incident infection was estimated using
      the Kaplan-Meier method.Results: The prevalence and incidence of the genital HPV
      types known to cause disease in males (HPV 16 and 6) was significantly higher
      among men from Brazil than men from Mexico. Prevalence and incidence of those
      genital HPV types in the United States varied between being comparable with those
      of Mexico or Brazil. Although genital HPV16 duration was significantly longer in
      Brazil (P = 0.04) compared with Mexico and the United States, HPV6 duration was
      shortest in Brazil (P = 0.03) compared with Mexico and the United
      States.Conclusions: Men in Brazil and Mexico often have similar, if not higher
      prevalence of HPV compared with men from the United States.Impact: Currently,
      there is no routine screening for genital HPV among males and while HPV is common
      in men, and most naturally clear the infection, a proportion of men do develop
      HPV-related diseases. Men may benefit from gender-neutral vaccine policies.
      Cancer Epidemiol Biomarkers Prev; 26(7); 1043-52. (c)2017 AACR.

PMID- 28446544
TI  - Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is
      Associated with Worse Survival.
AB  - Background: Lung cancer treatment has become increasingly dependent upon invasive
      biopsies to profile tumors for personalized therapy. Recently, tumor expression
      of programmed death-ligand 1 (PD-L1) has gained interest as a potential predictor
      of response to immunotherapy. Circulating biomarkers present an opportunity for
      tumor profiling without the risks of invasive procedures. We characterized PD-L1
      expression within populations of nucleated cells in the peripheral blood of lung
      cancer patients in hopes of expanding the role of liquid biopsy in this
      setting.Methods: Peripheral blood samples from a multi-institutional prospective
      study of patients with clinical diagnosis of lung cancer were subjected to
      cytomorphometric and immunohistochemical evaluation using single-cell, automated
      slide-based, digital pathology. PD-L1 expression was determined by
      immunofluorescence.Results: PD-L1 expression was detected within peripheral
      circulating cells associated with malignancy (CCAM) in 26 of 112 (23%) non-small
      cell lung cancer patients. Two distinct populations of nucleated,
      nonhematolymphoid, PD-L1-expressing cells were identified; cytokeratin positive
      (CK+, PD-L1+, CD45-) and cytokeratin negative (CK-, PD-L1+, CD45-) cells, both
      with cytomorphometric features (size, nuclear-to-cytoplasm ratio) consistent with
      tumor cells. Patients with >1.1 PD-L1(+) cell/mL (n = 14/112) experienced worse
      overall survival than patients with <=1.1 PD-L1(+) cell/mL (2-year OS: 31.2% vs.
      78.8%, P = 0.00159). In a Cox model adjusting for stage, high PD-L1(+) cell
      burden remained a significant predictor of mortality (HR = 3.85; 95% confidence
      interval, 1.64-9.09; P = 0.002).Conclusions: PD-L1 expression is detectable in
      two distinct cell populations in the peripheral blood of lung cancer patients and
      is associated with worse survival.Impact: These findings could represent a step
      forward in the development of minimally invasive liquid biopsies for the
      profiling of tumors. Cancer Epidemiol Biomarkers Prev; 26(7); 1139-45. (c)2017
      AACR.

PMID- 28446546
TI  - Conjunctival Ultraviolet Autofluorescence as a Measure of Past Sun Exposure in
      Children.
AB  - Background: Conjunctival ultraviolet autofluorescence (CUVAF) area detected from
      UVAF photographs is a recently developed potential marker for past sun exposure,
      but its relationship with sun-related factors has not been fully
      investigated.Methods: The study included 339 healthy children ages 5 to 15 years
      in Melbourne, Australia. Data were collected by questionnaire and examination at
      school. CUVAF area was measured using a computer program and analyzed as a
      continuous and dichotomous outcome (any/none).Results: Fifty-three children
      (15.6%) had detectable CUVAF, and the youngest age at which a child showed sun
      damage was 8 years. Compared with silicone skin cast score, there was good inter
      grader agreement on CUVAF grading, with Cohen kappa 0.85 [95% confidence interval
      (CI), 0.65-1.00] for total CUVAF area using both eye photographs. Perfect intra
      grader agreement was achieved. Fairer pigmentation, including medium/fair skin
      color [adjusted odds ratio (AOR), 3.42; 95% CI, 1.02-11.48 vs. dark/olive] and
      blue/gray eye color (AOR, 4.07; 95% CI, 1.73-9.55 vs. brown) was associated with
      increased odds of CUVAF. Increasing lifetime sunburn number (e.g., AOR, 2.89; 95%
      CI, 1.14-7.35 and 4.29; 1.04-17.76 for sunburns 2 to 4 and >= 5 times,
      respectively, vs. no sunburns, trend P = 0.004) and freckling by the end of last
      summer were associated with increased odds of CUVAF.Conclusions: CUVAF area can
      be an a priori objective measure of past sun exposure in pediatric populations
      for future research.Impact: To our knowledge, this is the first pediatric study
      that evaluated associations of sun-related risk factors with CUVAF. Cancer
      Epidemiol Biomarkers Prev; 26(7); 1146-53. (c)2017 AACR.

PMID- 28446547
TI  - An abnormal chamber-like structure after mitral valve replacement.

PMID- 28446545
TI  - A Pooled Analysis of 15 Prospective Cohort Studies on the Association between
      Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.
AB  - Background: Relationships between fruit, vegetable, and mature bean consumption
      and prostate cancer risk are unclear.Methods: We examined associations between
      fruit and vegetable groups, specific fruits and vegetables, and mature bean
      consumption and prostate cancer risk overall, by stage and grade, and for
      prostate cancer mortality in a pooled analysis of 15 prospective cohorts,
      including 52,680 total cases and 3,205 prostate cancer-related deaths among
      842,149 men. Diet was measured by a food frequency questionnaire or similar
      instrument at baseline. We calculated study-specific relative risks using Cox
      proportional hazards regression, and then pooled these estimates using a random
      effects model.Results: We did not observe any statistically significant
      associations for advanced prostate cancer or prostate cancer mortality with any
      food group (including total fruits and vegetables, total fruits, total
      vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato
      products), nor specific fruit and vegetables. In addition, we observed few
      statistically significant results for other prostate cancer outcomes. Pooled
      multivariable relative risks comparing the highest versus lowest quantiles across
      all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89
      to 1.09. There was no evidence of effect modification for any association by age
      or body mass index.Conclusions: Results from this large, international, pooled
      analysis do not support a strong role of collective groupings of fruits,
      vegetables, or mature beans in prostate cancer.Impact: Further investigation of
      other dietary exposures, especially indicators of bioavailable nutrient intake or
      specific phytochemicals, should be considered for prostate cancer risk. Cancer
      Epidemiol Biomarkers Prev; 26(8); 1276-87. (c)2017 AACR.

PMID- 28446549
TI  - Management of coronary artery disease with cardiac CT beyond gatekeeping.

PMID- 28446548
TI  - Regional left ventricular function does not predict survival in ischaemic
      cardiomyopathy after cardiac surgery.
AB  - OBJECTIVES: To define the prognostic contribution of global and regional left
      ventricular (LV) function measurements in patients with ischaemic cardiomyopathy
      randomised to coronary artery bypass graft surgery (CABG) with (n=501) or without
      (n=499) surgical ventricular reconstruction (SVR). METHODS: Novel multivariable
      methods to analyse global and regional LV systolic function were used to better
      formulate prediction models for long-term mortality following CABG with or
      without SVR in the entire cohort of 1000 randomised SVR hypothesis patients. Key
      clinical variables were included in the analysis. Regional function was
      classified according to the discreteness of anteroapical hypokinesia and akinesia
      into those most likely to benefit from SVR, those least likely and those felt to
      have intermediate likelihood of benefit from SVR. RESULTS: The most prognostic
      clinical variables identified in multivariable models include creatinine, LV end
      systolic volume index (ESVI), age and NYHA (New York Heart Association) class.
      Addition of LV ejection fraction, LV end-diastolic volume index and regional
      function assessment did not contribute additional power to the model. Subgroup
      analysis based on regional function did not identify a cohort in which SVR
      improved mortality. CONCLUSIONS: ESVI is the single parameter of LV function most
      predictive of mortality in patients with LV systolic dysfunction following CABG
      with or without SVR in multivariable models that include all key clinical and LV
      systolic function parameters. Assessment of regional cardiac function does not
      enhance prediction of mortality nor identify a subgroup for which SVR improves
      mortality. These results do not support elective addition of LV reconstruction
      surgery in patients undergoing CABG. TRIAL REGISTRATION NUMBER: NCT00023595.

PMID- 28446550
TI  - National Institute for Health and Care Excellence updates the stable chest pain
      guideline with radical changes to the diagnostic paradigm.
AB  - In the 2016 update of the stable chest pain guideline, the National Institute for
      Health and Care Excellence (NICE) has made radical changes to the diagnostic
      paradigm that it-like other international guidelines-had previously placed at the
      centre of its recommendations. No longer are quantitative assessments of the
      disease probability considered necessary to determine the need for diagnostic
      testing and the choice of test. Instead, the recommendation is for no diagnostic
      testing if chest pain is judged to be 'non-anginal' and CT coronary angiography
      (CTCA) in patients with 'typical' or 'atypical' chest pain with additional
      perfusion imaging only if there is uncertainty about the functional significance
      of coronary lesions. The new emphasis on anatomical-as opposed to functional
      testing is driven in large part by cost-effectiveness analysis and despite
      inevitable resource implications NICE calculates that annual savings for the
      population of England will be significant. In making CTCA the default diagnostic
      testing strategy in its updated chest pain guideline, NICE has responded
      emphatically to calls from trialists for CTCA to have a greater role in the
      diagnostic pathway of patients with suspected angina.

PMID- 28446553
TI  - Long-term change in reactance by forced oscillation technique correlates with
      FEV1 decline in moderate COPD patients.

PMID- 28446552
TI  - A European Respiratory Society technical standard: exhaled biomarkers in lung
      disease.
AB  - Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile
      organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other
      measurements. For EBC and for FeNO, official recommendations for standardised
      procedures are more than 10 years old and there is none for exhaled VOCs and
      particles. The aim of this document is to provide technical standards and
      recommendations for sample collection and analytic approaches and to highlight
      future research priorities in the field. For EBC and FeNO, new developments and
      advances in technology have been evaluated in the current document. This report
      is not intended to provide clinical guidance on disease diagnosis and
      management.Clinicians and researchers with expertise in exhaled biomarkers were
      invited to participate. Published studies regarding methodology of breath tests
      were selected, discussed and evaluated in a consensus-based manner by the Task
      Force members.Recommendations for standardisation of sampling, analysing and
      reporting of data and suggestions for research to cover gaps in the evidence have
      been created and summarised.Application of breath biomarker measurement in a
      standardised manner will provide comparable results, thereby facilitating the
      potential use of these biomarkers in clinical practice.

PMID- 28446554
TI  - Patient and partner empowerment programme for idiopathic pulmonary fibrosis.

PMID- 28446555
TI  - Higher serum 25(OH)D concentrations are associated with improved FEV1 and FVC in
      adolescence.
AB  - Vitamin D plays a role in the development of the immune system and the lung, as
      well as in airway remodelling. Therefore, this study investigated the association
      between serum 25-hydroxyvitamin D (25(OH)D) concentrations and spirometric lung
      function parameters at age 15 years.In the German birth cohorts GINIplus and
      LISAplus, lung function testing by spirometry and 25(OH)D measurements were
      performed during the 15-year follow-up examinations. Valid lung function
      measurements pre- and/or post-bronchodilation and serum 25(OH)D concentrations,
      which were adjusted for the date of blood sampling to account for seasonal
      variability, were available for 2607 adolescents. Associations between 25(OH)D
      concentrations and spirometric parameters were analysed using generalised
      additive models adjusted for confounding factors.Serum 25(OH)D concentrations
      were significantly associated with forced vital capacity (FVC), forced expiratory
      volume in 1 s (FEV1) and FEV1/FVC measured before bronchodilation after
      adjustment for potential confounders: FEV1 increased by 10 mL (95% CI 2-17), FVC
      by 20 mL (95% CI 12-28) and FEV1/FVC decreased by 0.177% (95% CI -0.286 to 
      0.067) per 10 nmol.L-1 increase in 25(OH)D concentrations. Flow rates (forced
      expiratory flow rates at 25, 50 and 75% of exhaled FVC (FEF25, FEF50, FEF75) and
      mean flow rate between 25 and 75% of FVC (FEF25-75)) were not associated with
      vitamin D. Similar associations were observed for lung function parameters
      measured after bronchodilation.Vitamin D concentrations are positively associated
      with volume-related lung function parameters pre- and post-bronchodilation,
      suggesting structural changes in peripheral airways.

PMID- 28446556
TI  - Bacteria-driven peribronchial lymphoid neogenesis in bronchiectasis and cystic
      fibrosis.
AB  - We aimed to characterise lymphoid neogenesis in bronchiectasis and cystic
      fibrosis (CF) lungs and to examine the role of bacterial infection.Lymphoid
      aggregates were examined using immunohistochemical staining and morphometric
      analysis in surgical lung sections obtained from nonsmokers and patients with
      bronchiectasis or CF. Sterile, Pseudomonas aeruginosa- or Staphylococcus aureus
      coated agarose beads were instilled intratracheally in mice. Kinetics of lymphoid
      neogenesis and chemokine expression were examined over 14 days.Lymphoid
      aggregates were scarce in human lungs of nonsmokers, but numerous peribronchial
      lymphoid aggregates containing B-lymphocytes, T-lymphocytes, germinal centres and
      high endothelial venules were found in bronchiectasis and CF. Mouse lungs
      contained no lymphoid aggregate at baseline. During persistent P. aeruginosa or
      S. aureus airway infection peribronchial lymphoid neogenesis occurred. At day 14
      after instillation, lymphoid aggregates expressed markers of tertiary lymphoid
      organs and the chemokines CXCL12 and CXCL13. The airway epithelium was an
      important site of CXCL12, CXCL13 and interleukin-17A expression, which began at
      day 1 after instillation.Peribronchial tertiary lymphoid organs are present in
      bronchiectasis and in CF, and persistent bacterial infection triggered
      peribronchial lymphoid neogenesis in mice. Peribronchial localisation of tertiary
      lymphoid organs and epithelial expression of chemokines suggest roles for airway
      epithelium in lymphoid neogenesis.

PMID- 28446557
TI  - Circulating miRNAs from imprinted genomic regions are associated with peripheral
      muscle strength in COPD patients.

PMID- 28446558
TI  - Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis
      bronchiectasis lung.
AB  - To characterise Pseudomonas aeruginosa populations during chronic lung infections
      of non-cystic fibrosis bronchiectasis patients, we used whole-genome sequencing
      to 1) assess the diversity of P. aeruginosa and the prevalence of multilineage
      infections; 2) seek evidence for cross-infection or common source acquisition;
      and 3) characterise P. aeruginosa adaptations.189 isolates, obtained from the
      sputa of 91 patients attending 16 adult bronchiectasis centres in the UK, were
      whole-genome sequenced.Bronchiectasis isolates were representative of the wider
      P. aeruginosa population. Of 24 patients from whom multiple isolates were
      examined, there were seven examples of multilineage infections, probably arising
      from multiple infection events. The number of nucleotide variants between genomes
      of isolates from different patients was in some cases similar to the variations
      observed between isolates from individual patients, implying the possible
      occurrence of cross-infection or common source acquisition.Our data indicate that
      during infections of bronchiectasis patients, P. aeruginosa populations adapt by
      accumulating loss-of-function mutations, leading to changes in phenotypes
      including different modes of iron acquisition and variations in biofilm
      associated polysaccharides. The within-population diversification suggests that
      larger scale longitudinal surveillance studies will be required to capture cross
      infection or common source acquisition events at an early stage.

PMID- 28446559
TI  - Burden of non-tuberculous mycobacterial pulmonary disease in Germany.
AB  - The objective of this study was to estimate the burden of disease in incident
      patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD).A sample
      of 7 073 357 anonymised persons covered by German public statutory health
      insurances was used to identify patients with NTM-PD. In total, 125 patients with
      newly diagnosed NTM-PD in 2010 and 2011 were matched with 1250 control patients
      by age, sex and Charlson Comorbidity Index, and followed for 39 months.The
      incidence rate for NTM-PD was 2.6 per 100 000 insured persons (95% CI 2.2-3.1).
      The mortality rate for patients with NTM-PD and the control group in the
      observational period was 22.4% and 6%, respectively (p<0.001). Mean direct
      expenditure per NTM-PD patient was ?39 559.60 (95% CI 26 916.49-52 202.71),
      nearly 4-fold (3.95, 95% CI 3.73-4.19) that for a matched control (?10 006.71,
      95% CI 8907.24-11 106.17). Hospitalisations were three times higher in the NTM-PD
      group and accounted for 63% of the total costs. Attributable annual direct costs
      and indirect work-loss costs in NTM-PD patients were ?9093.20 and ?1221.05 per
      control patient, respectively. Only 74% of NTM-PD patients received antibiotics
      and nearly 12% were prescribed macrolide monotherapy.Although NTM-PD is
      considered rare, the attributable mortality and financial burden in Germany are
      high. Efforts to heighten awareness of appropriate therapy are urgently needed.

PMID- 28446560
TI  - GOLD 2017 on the way to a phenotypic approach? Analysis from the Phenotypes of
      COPD in Central and Eastern Europe (POPE) Cohort.

PMID- 28446561
TI  - Therapeutic drug monitoring to prevent acquired drug resistance of
      fluoroquinolones in the treatment of tuberculosis.

PMID- 28446562
TI  - Therapeutic drug monitoring to prevent acquired drug resistance of
      fluoroquinolones in the treatment of tuberculosis.

PMID- 28446563
TI  - Nontuberculous mycobacterial pulmonary disease: an increasing burden with
      substantial costs.

PMID- 28446564
TI  - Lung lymphoid neogenesis in cystic fibrosis: a model of adaptive responses to
      bacteria?

PMID- 28446565
TI  - Murinization and H Chain Isotype Matching of the Anti-GITR Antibody DTA-1 Reduces
      Immunogenicity-Mediated Anaphylaxis in C57BL/6 Mice.
AB  - Recent advances in immuno-oncology have shown that the immune system can be
      activated to induce long-term, durable antitumor responses. For immuno-oncology
      drug development, immune activation is often explored using rat Abs in
      immunocompetent mouse models. Although these models can be used to show efficacy,
      antidrug immune responses to experimental protein-based therapeutics can arise.
      Immunogenicity of surrogate Abs may therefore represent an important obstacle to
      the evaluation of the antitumor efficacy of immunomodulator Abs in syngeneic
      models. A recent publication has shown that anti-glucocorticoid-induced TNFR
      family-related protein agonistic Ab DTA-1 (rat or murinized IgG2a) can induce the
      development of anaphylaxis in C57BL/6 mice upon repeated i.p. dosing because of
      an anti-idiotypic anti-drug Ab immune response. This study was undertaken to
      address the impact of the immunogenicity derived from the Fc and variable
      domains. To this end, chimerized (rat V domains/mouse constant regions) and
      murinized (95% mouse sequence) DTA-1-based surrogate Abs with a murine IgG2c H
      chain isotype were created. Chimerization and murinization of DTA-1 did not
      affect receptor binding and glucocorticoid-induced TNFR family-related protein
      induced T cell agonistic properties. Similar in vivo antitumor efficacy and
      intratumoral CD8+/regulatory T cells were also observed. Finally, treatment of
      C57BL/6 mice with the chimerized and murinized DTA-1 Abs on a C57BL/6-matched
      IgG2c isotype resulted in reduced development and severity of anaphylaxis as
      measured by decline of body temperature, behavioral effects, serum IL-4, IgE, and
      anti-drug Ab levels. These results suggest that careful murinization and
      selection of a strain-matched H chain isotype are critical to generate ideal
      surrogate Abs for testing immuno-oncology mechanisms in vivo.

PMID- 28446566
TI  - Induction of Adaptive Immunity Leads to Nigrostriatal Disease Progression in MPTP
      Mouse Model of Parkinson's Disease.
AB  - Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is
      the most widely used animal model for Parkinson's disease (PD), it is known that
      nigrostriatal pathologies do not persist in the acute MPTP mouse model. This
      study highlights the importance of adaptive immunity in driving persistent and
      progressive disease in acute MPTP-intoxicated mice. Although marked infiltration
      of T cells into the nigra was found on 1 d of MPTP insult, T cell infiltration
      decreased afterward, becoming normal on 30 d of insult. Interestingly, twice
      weekly supplementation of RANTES and eotaxin, chemokines that are involved in T
      cell trafficking, drove continuous T cell infiltration to the nigra and incessant
      glial inflammation. Supplementation of RANTES and eotaxin was also associated
      with the induction of nigral alpha-synuclein pathology, persistent loss of
      dopaminergic neurons and striatal neurotransmitters, and continuous impairment of
      motor functions in MPTP-intoxicated mice. In contrast, supplementation of TNF
      alpha and IL-1beta, widely studied proinflammatory cytokines, did not induce
      persistent disease in MPTP-insulted mice. Our results suggest that induction of
      adaptive immunity by RANTES and eotaxin could hold the key for driving persistent
      nigrostriatal pathologies in the MPTP mouse model, and that targeting these
      factors may halt disease progression in PD patients.

PMID- 28446567
TI  - Determination of a Key Antigen for Immunological Intervention To Target the
      Latent Stage of Toxoplasma gondii.
AB  - Toxoplasma gondii, an obligate intracellular protozoan parasite, establishes a
      chronic infection by forming cysts preferentially in the brain. Up to one third
      of the human population worldwide is estimated to be chronically infected with
      this parasite. However, there is currently no drug effective against the cyst
      form of the parasite. In addition, the protective immunity against the cysts
      remains largely unknown. We analyzed the molecular mechanisms by which the immune
      system detects host cells harboring the cysts to eliminate the latent stage of
      the parasite using mice with the H-2d haplotype, which are genetically resistant
      to the infection. Our study revealed that CD8+ immune T cells bearing TCR
      Vbeta8.1, 8.2 chain have a potent activity to remove T. gondii cysts from the
      brain. Our studies also uncovered that H-2Ld is the major Ag-presenting molecule
      to CD8+ T cells for initiating cyst elimination, and that CD8+Vbeta8.1, 8.2+
      immune T cells recognize the N-terminal region (aa 41-152) of dense granule
      protein 6 (GRA6Nt) of the parasite presented by the H-2Ld molecule. Furthermore,
      CD8+ immune T cells induced by immunization with recombinant GRA6Nt were
      eventually capable of removing the cysts from the brain when transferred to
      infected immunodeficient mice lacking T cells. Thus, GRA6Nt is a novel and potent
      Ag to activate CD8+ T cells capable of removing T. gondii cysts. These
      observations offer a basis for immunological intervention to combat chronic
      infection with T. gondii by targeting the persistent cysts of the parasite.

PMID- 28446568
TI  - Lis1 Regulates Germinal Center B Cell Antigen Acquisition and Affinity
      Maturation.
AB  - The germinal center (GC) is the site where activated B cells undergo rapid
      expansions, somatic hypermutation, and affinity maturation. Affinity maturation
      is a process of Ag-driven selection. The amount of Ag acquired and displayed by
      GC B cells determines whether it can be positively selected, and therefore Ag
      acquisition has to be tightly regulated to ensure the efficient affinity
      maturation. Cell expansion provides sufficient quantity of GC B cells and Abs,
      whereas affinity maturation improves the quality of Abs. In this study, we found
      that Lis1 is a cell-intrinsic regulator of Ag acquisition capability of GC B
      cells. Lack of Lis1 resulted in redistribution of polymerized actin and
      accumulation of F-actin at uropod; larger amounts of Ags were acquired and
      displayed by GC B cells, which presumably reduced the selection stringency.
      Affinity maturation was thus compromised in Lis1-deficient mice. Consistently,
      overexpression of Lis1 in GC B cells led to less Ag acquisition and display.
      Additionally, Lis1 is required for GC B cell expansion, and Lis1 deficiency
      blocked the cell cycle at the mitotic phase and GC B cells were prone to
      apoptosis. Overall, we suggest that Lis1 is required for GC B cell expansion,
      affinity maturation, and maintaining functional intact GC response, thus ensuring
      both the quantity and quality of Ab response.

PMID- 28446569
TI  - Differentiated Levels of Ganciclovir Resistance Conferred by Mutations at Codons
      591 to 603 of the Cytomegalovirus UL97 Kinase Gene.
AB  - Diagnostic mutations in the cytomegalovirus UL97 kinase gene are used to assess
      the level of associated ganciclovir resistance and therapeutic options. The best
      known mutations at codons 460, 520, or 591 to 607 individually confer 5- to 10
      fold-decreased ganciclovir susceptibility, except that a 3-fold decrease occurs
      in the case of the amino acid substitution C592G. Less common point and in-frame
      deletion mutations at codons 591 to 603 remain incompletely characterized. The
      ganciclovir susceptibilities of 17 mutants in this codon range were evaluated by
      use of the same recombinant phenotyping system and extensive assay replicates in
      two types of cell cultures. Amino acid substitutions K599E and T601M conferred no
      ganciclovir resistance, while A591V conferred 3.8-fold-decreased susceptibility.
      In-frame deletions of three or more codons conferred at least 8-fold-increased
      ganciclovir resistance, while the level of resistance conferred by one- or two
      codon deletions varied from 4- to 10-fold, depending on their location. Measured
      levels of ganciclovir resistance were closely comparable when assays were
      performed in either fibroblasts or modified retinal epithelial cells. The
      significant revision of a few previously published resistance phenotypes and the
      new data strengthen the interpretation of genotypic testing for cytomegalovirus
      drug resistance.

PMID- 28446570
TI  - Prevalence and Outcomes of Achromobacter Species Infections in Adults with Cystic
      Fibrosis: a North American Cohort Study.
AB  - Achromobacter species are increasingly being detected in cystic fibrosis (CF)
      patients, with an unclear epidemiology and impact. We studied a cohort of
      patients attending a Canadian adult CF clinic who had positive sputum cultures
      for Achromobacter species in the period from 1984 to 2013. Infection was
      categorized as transient or persistent (>=50% positive cultures for 1 year).
      Those with persistent infection were matched 2:1 with age-, sex-, and time
      matched controls without a history of Achromobacter infection, and mixed-effects
      models were used to assess pulmonary exacerbation (PEx) frequency and lung
      function decline. Isolates from a biobank were retrospectively assessed,
      identified to the species level by nrdA sequencing, and genotyped using pulsed
      field gel electrophoresis (PFGE). Thirty-four patients (11% of those in our
      clinic), with a median age of 24 years (interquartile range [IQR], 20.3 to 29.8
      years), developed Achromobacter infection. Ten patients (29%) developed
      persistent infection. Persistence did not denote permanence, as most patients
      ultimately cleared infection, often after years. Patients were more likely to
      experience PEx at incident isolation than at prior or subsequent visits (odds
      ratio [OR], 2.7 [95% confidence interval {CI}, 1.2 to 6.7]; P = 0.03). Following
      persistent infection, there was no difference in annual lung function decline (
      1.08% [95% CI, -2.73 to 0.57%] versus -2.74% [95% CI, -4.02 to 1.46%]; P = 0.12)
      or the odds of PEx (OR, 1.21 [95% CI, 0.45 to 3.28]; P = 0.70). Differential
      virulence among Achromobacter species was not observed, and no cases of
      transmission occurred. We demonstrated that incident Achromobacter infection was
      associated with a greater risk of PEx; however, neither transient nor chronic
      infection was associated with a worsened long-term prognosis. Large, multicenter
      studies are needed to clarify the clinical impact, natural history, and
      transmissibility of Achromobacter.

PMID- 28446571
TI  - Core Genome Multilocus Sequence Typing Scheme for Stable, Comparative Analyses of
      Campylobacter jejuni and C. coli Human Disease Isolates.
AB  - Human campylobacteriosis, caused by Campylobacter jejuni and C. coli, remains a
      leading cause of bacterial gastroenteritis in many countries, but the
      epidemiology of campylobacteriosis outbreaks remains poorly defined, largely due
      to limitations in the resolution and comparability of isolate characterization
      methods. Whole-genome sequencing (WGS) data enable the improvement of sequence
      based typing approaches, such as multilocus sequence typing (MLST), by
      substantially increasing the number of loci examined. A core genome MLST (cgMLST)
      scheme defines a comprehensive set of those loci present in most members of a
      bacterial group, balancing very high resolution with comparability across the
      diversity of the group. Here we propose a set of 1,343 loci as a human
      campylobacteriosis cgMLST scheme (v1.0), the allelic profiles of which can be
      assigned to core genome sequence types. The 1,343 loci chosen were a subset of
      the 1,643 loci identified in the reannotation of the genome sequence of C. jejuni
      isolate NCTC 11168, chosen as being present in >95% of draft genomes of 2,472
      representative United Kingdom campylobacteriosis isolates, comprising 2,207
      (89.3%) C. jejuni isolates and 265 (10.7%) C. coli isolates. Validation of the
      cgMLST scheme was undertaken with 1,478 further high-quality draft genomes,
      containing 150 or fewer contiguous sequences, from disease isolate collections:
      99.5% of these isolates contained >=95% of the 1,343 cgMLST loci. In addition to
      the rapid and effective high-resolution analysis of large numbers of diverse
      isolates, the cgMLST scheme enabled the efficient identification of very closely
      related isolates from a well-defined single-source campylobacteriosis outbreak.

PMID- 28446572
TI  - Evaluation of the Accelerate Pheno System for Fast Identification and
      Antimicrobial Susceptibility Testing from Positive Blood Cultures in Bloodstream
      Infections Caused by Gram-Negative Pathogens.
AB  - Bloodstream infections (BSI) are an important cause of morbidity and mortality.
      Increasing rates of antimicrobial-resistant pathogens limit treatment options,
      prompting an empirical use of broad-range antibiotics. Fast and reliable
      diagnostic tools are needed to provide adequate therapy in a timely manner and to
      enable a de-escalation of treatment. The Accelerate Pheno system (Accelerate
      Diagnostics, USA) is a fully automated test system that performs both
      identification and antimicrobial susceptibility testing (AST) directly from
      positive blood cultures within approximately 7 h. In total, 115 episodes of BSI
      with Gram-negative bacteria were included in our study and compared to
      conventional culture-based methods. The Accelerate Pheno system correctly
      identified 88.7% (102 of 115) of all BSI episodes and 97.1% (102 of 105) of
      isolates that are covered by the system's identification panel. The Accelerate
      Pheno system generated an AST result for 91.3% (95 of 104) samples in which the
      Accelerate Pheno system identified a Gram-negative pathogen. The overall category
      agreement between the Accelerate Pheno system and culture-based AST was 96.4%,
      the rates for minor discrepancies 1.4%, major discrepancies 2.3%, and very major
      discrepancies 1.0%. Of note, ceftriaxone, piperacillin-tazobactam, and carbapenem
      resistance was correctly detected in blood culture specimens with extended
      spectrum beta-lactamase-producing Escherichia coli (n = 7) and multidrug
      resistant Pseudomonas aeruginosa (n = 3) strains. The utilization of the
      Accelerate Pheno system reduced the time to result for identification by 27.49 h
      (P < 0.0001) and for AST by 40.39 h (P < 0.0001) compared to culture-based
      methods in our laboratory setting. In conclusion, the Accelerate Pheno system
      provided fast, reliable results while significantly improving turnaround time in
      blood culture diagnostics of Gram-negative BSI.

PMID- 28446573
TI  - Serologic Testing for Zika Virus: Comparison of Three Zika Virus IgM-Screening
      Enzyme-Linked Immunosorbent Assays and Initial Laboratory Experiences.
AB  - Serologic evaluation for Zika virus (ZIKV) infection currently includes an
      initial screen using an anti-ZIKV IgM antibody capture enzyme-linked
      immunosorbent assay (MAC-ELISA) followed by supplemental testing of specimens
      with nonnegative results by a plaque reduction neutralization test (PRNT). We
      compared the performance characteristics of three ELISAs for the detection of IgM
      class antibodies to ZIKV, including the Centers for Disease Control and
      Prevention (CDC) Zika MAC-ELISA, the InBios ZIKV Detect MAC-ELISA, and the
      Euroimmun anti-Zika Virus IgM ELISA. Additionally, we present our initial
      experiences with ZIKV serologic testing from a national reference laboratory
      perspective. Using both retrospectively and prospectively collected specimens
      from patients with possible ZIKV infection, we show that the CDC and InBios MAC
      ELISAs perform comparably to each other, with positive agreement, negative
      agreement, and interrater kappa values ranging from 87.5% to 93.1%, 95.7% to
      98.5%, and 0.52 to 0.83, respectively. In contrast, comparison of the Euroimmun
      ZIKV ELISA to either the CDC or InBios MAC-ELISAs resulted in positive agreement,
      negative agreement, and interrater kappa values ranging from 17.9% to 42.9%,
      91.7% to 98.6%, and 0.10 to 0.39, respectively. Among the 19 prospective samples
      submitted for PRNT, nine were negative, eight specimens had neutralizing
      antibodies to a flavivirus (unable to be identified), and one sample each was
      confirmed for ZIKV or dengue virus infection. This study highlights the ongoing
      challenges associated with serologic diagnosis of ZIKV infection. Although the
      availability of a commercial serologic test for ZIKV has greatly expanded the
      national capacity for such testing, the need to further characterize and improve
      these assays, particularly with regard to specificity, remains.

PMID- 28446574
TI  - Use of GeneXpert Remnants for Drug Resistance Profiling and Molecular
      Epidemiology of Tuberculosis in Libreville, Gabon.
AB  - Multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of
      Mycobacterium tuberculosis pose major problems for global health. The GeneXpert
      MTB/RIF (Xpert) assay rapidly detects resistance to rifampin (RIFr), but for
      detection of the additional resistance that defines MDR-TB (MDR tuberculosis) and
      XDR-TB, and for molecular epidemiology, specimen cultures and a biosafe
      infrastructure are generally required. We sought to determine whether the
      remnants of sputa prepared for the Xpert assay could be used directly to find
      mutations associated with drug resistance and to study molecular epidemiology,
      thus providing precise characterization of MDR-TB cases in countries lacking
      biosafety level 3 (BSL3) facilities for M. tuberculosis cultures. After sputa
      were processed and run on the Xpert instrument, the leftovers of the samples
      prepared for the Xpert assay were used for PCR amplification and sequencing or
      for a line probe assay to detect mutations associated with resistance to
      additional drugs, as well as for molecular epidemiology with spoligotyping and
      selective mycobacterial interspersed repetitive-unit-variable-number tandem
      repeat (MIRU-VNTR) typing. Of 130 sputum samples from Gabon tested with the Xpert
      assay, 124 yielded interpretable results; 21 (17%) of these were determined to be
      RIFr Amplification and sequencing or a line probe assay of the Xpert remnants
      confirmed 18/21 samples as MDR, corresponding to 12/116 (9.5%) new and 6/8 (75%)
      previously treated TB patients. Spoligotyping and MIRU typing with hypervariable
      loci identified an MDR Beijing strain present in five samples. We conclude that
      the remnants of samples processed for the Xpert assay can be used in PCRs to find
      mutations associated with the resistance to the additional drugs that defines MDR
      and XDR-TB and to study molecular epidemiology without the need for culturing or
      a biosafe infrastructure.

PMID- 28446575
TI  - Evaluation of StrepBSelect Chromogenic Medium and the Fast-Track Diagnostics
      Group B Streptococcus (GBS) Real-Time PCR Assay Compared to Routine Culture for
      Detection of GBS during Antepartum Screening.
AB  - Life-threatening infection in neonates due to group B Streptococcus (GBS) is
      preventable by screening of near-term pregnant women and treatment at delivery. A
      total of 295 vaginal-rectal swabs were collected from women attending antepartum
      clinics in Calgary, Alberta, Canada. GBS colonization was detected by the
      standard culture method (Strep B Carrot Broth subcultured to blood agar with a
      neomycin disk) and compared to recovery with Strep Group B Broth (Dalynn
      Biologicals) subcultured to StrepBSelect chromogenic medium (CM; Bio-Rad
      Laboratories) and the Fast-Track Diagnostics GBS real-time PCR (quantitative PCR
      [qPCR]) assay (Phoenix Airmid Biomedical Corp.) performed with broth-enriched
      samples and the Abbott m2000sp/m2000rt system. A total of 62/295 (21%) women were
      colonized with GBS; 58 (19.7%) cases were detected by standard culture, while CM
      and qPCR each found 61 (20.7%) cases. The qPCR and CM were similar in
      performance, with sensitivities, specificities, and positive and negative
      predictive values of 98.4 and 98.4%, 99.6 and 99.6%, 98.4 and 98.4%, and 99.6 and
      99.6%, respectively, compared to routine culture. Both qPCR and CM would allow
      more rapid reporting of routine GBS screening results than standard culture.
      Although the cost per test was similar for standard culture and CM, the routine
      use of qPCR would cost approximately four times as much as culture-based
      detection. Laboratories worldwide should consider implementing one of the newer
      methods for primary GBS testing, depending on the cost limitations of different
      health care jurisdictions.

PMID- 28446576
TI  - Diagnostic Value of Galactomannan Antigen Test in Serum and Bronchoalveolar
      Lavage Fluid Samples from Patients with Nonneutropenic Invasive Pulmonary
      Aspergillosis.
AB  - The objective of this study was to compare the diagnostic value of galactomannan
      (GM) detection in bronchoalveolar lavage fluid (BALF) and serum samples from
      nonneutropenic patients with invasive pulmonary aspergillosis (IPA) and determine
      the optimal BALF GM cutoff value for pulmonary aspergillosis. GM detection in
      BALF and serum samples was performed by enzyme-linked immunosorbent assay (ELISA)
      in 128 patients with clinically suspected nonneutropenic pulmonary aspergillosis
      between June 2014 and June 2016. On the basis of the clinical and pathological
      diagnoses, 8 patients were excluded because their diagnosis was uncertain. The
      remaining 120 patients were diagnosed with either IPA (n = 37), community
      acquired pneumonia (CAP; n = 59), noninfectious diseases (n = 19), or
      tuberculosis (n = 5). At a cutoff optical density index (ODI) value of >=0.5, the
      sensitivity of BALF GM detection was much higher than that of serum GM detection
      (75.68% versus 37.84%; P = 0.001), but there was no significant difference
      between their specificities (80.72% versus 87.14%; P = 0.286). At a cutoff value
      of >=1.0, the sensitivity of BALF GM detection was still much higher than that of
      serum GM detection (64.86% versus 24.32%; P < 0.001), and their specificities
      were similar (90.36% versus 95.71%; P = 0.202). Receiver operating characteristic
      (ROC) curve analysis showed that when the BALF GM detection cutoff value was 0.7,
      its diagnostic value for pulmonary aspergillosis was optimized, and the
      sensitivity and specificity reached 72.97% and 89.16%, respectively. BALF GM
      detection was valuable for the diagnosis of IPA in nonneutropenic patients, and
      its diagnostic value was superior to that of serum GM detection. The optimal BALF
      GM cutoff value was 0.7.

PMID- 28446577
TI  - Population Dynamics of Staphylococcus aureus in Cystic Fibrosis Patients To
      Determine Transmission Events by Use of Whole-Genome Sequencing.
AB  - Strict infection control practices have been implemented for health care visits
      by cystic fibrosis (CF) patients in an attempt to prevent transmission of
      important pathogens. This study used whole-genome sequencing (WGS) to determine
      strain relatedness and assess population dynamics of Staphylococcus aureus
      isolates from a cohort of CF patients as assessed by strain relatedness. A total
      of 311 S. aureus isolates were collected from respiratory cultures of 115 CF
      patients during a 22-month study period. Whole-genome sequencing was performed,
      and using single nucleotide polymorphism (SNP) analysis, phylogenetic trees were
      assembled to determine relatedness between isolates. Methicillin-resistant
      Staphylococcus aureus (MRSA) phenotypes were predicted using PPFS2 and compared
      to the observed phenotype. The accumulation of SNPs in multiple isolates obtained
      over time from the same patient was examined to determine if a genomic molecular
      clock could be calculated. Pairs of isolates with <=71 SNP differences were
      considered to be the "same" strain. All of the "same" strain isolates were either
      from the same patient or siblings pairs. There were 47 examples of patients being
      superinfected with an unrelated strain. The predicted MRSA phenotype was accurate
      in all but three isolates. Mutation rates were unable to be determined because
      the branching order in the phylogenetic tree was inconsistent with the order of
      isolation. The observation that transmissions were identified between sibling
      patients shows that WGS is an effective tool for determining transmission between
      patients. The observation that transmission only occurred between siblings
      suggests that Staphylococcus aureus acquisition in our CF population occurred
      outside the hospital environment and indicates that current infection prevention
      efforts appear effective.

PMID- 28446578
TI  - Brain negativity as an indicator of predictive error processing: the contribution
      of visual action effect monitoring.
AB  - The error (related) negativity (Ne/ERN) is an event-related potential in the
      electroencephalogram (EEG) correlating with error processing. Its conditions of
      appearance before terminal external error information suggest that the Ne/ERN is
      indicative of predictive processes in the evaluation of errors. The aim of the
      present study was to specifically examine the Ne/ERN in a complex motor task and
      to particularly rule out other explaining sources of the Ne/ERN aside from error
      prediction processes. To this end, we focused on the dependency of the Ne/ERN on
      visual monitoring about the action outcome after movement termination but before
      result feedback (action effect monitoring). Participants performed a semi-virtual
      throwing task by using a manipulandum to throw a virtual ball displayed on a
      computer screen to hit a target object. Visual feedback about the ball flying to
      the target was masked to prevent action effect monitoring. Participants received
      a static feedback about the action outcome (850 ms) after each trial. We found a
      significant negative deflection in the average EEG curves of the error trials
      peaking at ~250 ms after ball release, i.e., before error feedback. Furthermore,
      this Ne/ERN signal did not depend on visual ball-flight monitoring after release.
      We conclude that the Ne/ERN has the potential to indicate error prediction in
      motor tasks and that it exists even in the absence of action effect
      monitoring.NEW & NOTEWORTHY In this study, we are separating different kinds of
      possible contributors to an electroencephalogram (EEG) error correlate (Ne/ERN)
      in a throwing task. We tested the influence of action effect monitoring on the
      Ne/ERN amplitude in the EEG. We used a task that allows us to restrict movement
      correction and action effect monitoring and to control the onset of result
      feedback. We ascribe the Ne/ERN to predictive error processing where a conscious
      feeling of failure is not a prerequisite.

PMID- 28446579
TI  - Modulation of long-latency afferent inhibition by the amplitude of sensory
      afferent volley.
AB  - Long-latency afferent inhibition (LAI) is the inhibition of the transcranial
      magnetic stimulation (TMS) motor-evoked potentials (MEP) by the sensory afferent
      volley following electrical stimulation of a peripheral nerve. It is unknown how
      the activation of sensory afferent fibers relates to the magnitude of LAI. This
      study investigated the relationship between LAI and the sensory nerve action
      potentials (SNAP) from the median nerve (MN) and the digital nerves (DN) of the
      second digit. LAI was obtained by delivering nerve stimulation 200 ms before a
      TMS pulse delivered over the motor cortex. Experiment 1 assessed the magnitude of
      LAI following stimulation of the contralateral MN or DN using nerve stimulus
      intensities relative to the maximum SNAP (SNAPmax) of that nerve and two TMS
      intensities (0.5- and 1-mV MEP). Results indicate that MN LAI is maximal at ~50%
      SNAPmax, when presumably all sensory afferents are recruited for TMS of 0.5-mV
      MEP. For DN, LAI appears at ~50% SNAPmax and does not increase with further
      recruitment of sensory afferents. Experiment 2 investigated the magnitude of LAI
      following ipsilateral nerve stimulation at intensities relative to SNAPmax
      Results show minimal LAI evoked by ipsilateral MN and no LAI following
      ipsilateral DN stimulation. Implications for future studies investigating LAI
      include adjusting nerve stimulation to 50% SNAPmax to obtain maximal LAI.
      Additionally, MN LAI can be used as a marker for neurological disease or injury
      by using a nerve stimulation intensity that can evoke a depth of LAI capable of
      increasing or decreasing.NEW & NOTEWORTHY This is the first investigation of the
      relationship between long-latency afferent inhibition (LAI) and the sensory
      afferent volley. Differences exist between median and digital nerve LAI. For the
      median nerve, LAI increases until all sensory fibers are presumably recruited. In
      contrast, digital nerve LAI does not increase with the recruitment of additional
      sensory fibers but rather is present when a given volume of sensory afferent
      fibers is recruited (~50% of maximum sensory nerve action potential). This novel
      data provide practical guidelines and contribute to our understanding of the
      mechanisms underlying LAI.

PMID- 28446580
TI  - Entrainment of visual steady-state responses is modulated by global spatial
      statistics.
AB  - The rhythmic delivery of visual stimuli evokes large-scale neuronal entrainment
      in the form of steady-state oscillatory field potentials. The spatiotemporal
      properties of stimulus drive appear to constrain the relative degrees of neuronal
      entrainment. Specific frequency ranges, for example, are uniquely suited for
      enhancing the strength of stimulus-driven brain oscillations. When it comes to
      the nature of the visual stimulus itself, studies have used a plethora of inputs
      ranging from spatially unstructured empty fields to simple contrast patterns
      (checkerboards, gratings, stripes) and complex arrays (human faces, houses,
      natural scenes). At present, little is known about how the global spatial
      statistics of the input stimulus influence entrainment of scalp-recorded
      electrophysiological signals. In this study, we used rhythmic entrainment source
      separation of scalp EEG to compare stimulus-driven phase alignment for distinct
      classes of visual inputs, including broadband spatial noise ensembles with
      varying second-order statistics, natural scenes, and narrowband sine-wave
      gratings delivered at a constant flicker frequency. The relative magnitude of
      visual entrainment was modulated by the global properties of the driving
      stimulus. Entrainment was strongest for pseudo-naturalistic broadband visual
      noise patterns in which luminance contrast is greatest at low spatial frequencies
      (a power spectrum slope characterized by 1/f-2).NEW & NOTEWORTHY Rhythmically
      modulated visual stimuli entrain the activity of neuronal populations, but the
      effect of global stimulus statistics on this entrainment is unknown. We assessed
      entrainment evoked by 1) visual noise ensembles with different spectral slopes,
      2) complex natural scenes, and 3) narrowband sinusoidal gratings. Entrainment was
      most effective for broadband noise with naturalistic luminance contrast. This
      reveals some global properties shaping stimulus-driven brain oscillations in the
      human visual system.

PMID- 28446581
TI  - Cl- channel is required for CXCL10-induced neuronal activation and itch response
      in a murine model of allergic contact dermatitis.
AB  - Persistent itch often accompanies allergic contact dermatitis (ACD), but the
      underlying mechanisms remain largely unexplored. We previously demonstrated that
      CXCL10/CXCR3 signaling activated a subpopulation of cutaneous primary sensory
      neurons and mediated itch response after contact hypersensitivity (CHS), a murine
      model of ACD, induced by squaric acid dibutylester. The purpose of this study was
      to determine the ionic mechanisms underlying CXCL10-induced neuronal activation
      and allergic itch. In whole cell recordings, CXCL10 triggered a current in dorsal
      root ganglion (DRG) neurons innervating the area of CHS. This current was
      modulated by intracellular Cl- and blocked by the general Cl- channel inhibitors.
      Moreover, increasing Ca2+ buffering capacity reduced this current. In addition,
      blockade of Cl- channels significantly suppressed CXCL10-induced Ca2+ response.
      In behavioral tests, injection of CXCL10 into CHS site exacerbated itch-related
      scratching behaviors. Moreover, the potentiating behavioral effects of CXCL10
      were attenuated by either of two Cl- channel blockers. Thus we suggest that the
      Cl- channel acts as a downstream target mediating the excitatory and pruritic
      behavioral effects of CXCL10. Cl- channels may provide a promising therapeutic
      target for the treatment of allergic itch in which CXCL10/CXCR3 signaling may
      participate.NEW & NOTEWORTHY The ionic mechanisms underlying CXCL10-induced
      neuronal activation and allergic itch are largely unexplored. This study revealed
      that CXCL10 evoked an ionic current mainly carried by Cl- channels. We suggest
      that Cl- channels are likely key molecular candidates responsible for the CXCL10
      evoked neuronal activation and itch-like behaviors in a murine model of allergic
      contact dermatitis induced by the antigen squaric acid dibutylester. Cl- channels
      may emerge as a promising drug target for the treatment of allergic itch in which
      CXCL10/CXCR3 signaling may participate.

PMID- 28446582
TI  - Auditory fear conditioning modifies steady-state evoked potentials in the rat
      inferior colliculus.
AB  - The rat inferior colliculus (IC) is a major midbrain relay for ascending inputs
      from the auditory brain stem and has been suggested to play a key role in the
      processing of aversive sounds. Previous studies have demonstrated that auditory
      fear conditioning (AFC) potentiates transient responses to brief tones in the IC,
      but it remains unexplored whether AFC modifies responses to sustained periodic
      acoustic stimulation-a type of response called the steady-state evoked potential
      (SSEP). Here we used an amplitude-modulated tone-a 10-kHz tone with a sinusoidal
      amplitude modulation of 53.7 Hz-as the conditioning stimulus (CS) in an AFC
      protocol (5 CSs per day in 3 consecutive days) while recording local field
      potentials (LFPs) from the IC. In the preconditioning session (day 1), the CS
      elicited prominent 53.7-Hz SSEPs. In the training session (day 2), foot shocks
      occurred at the end of each CS (paired group) or randomized in the inter-CS
      interval (unpaired group). In the test session (day 3), SSEPs markedly differed
      from preconditioning in the paired group: in the first two trials the phase to
      which the SSEP coupled to the CS amplitude envelope shifted ~90 degrees ; in the
      last two trials the SSEP power and the coherence of SSEP with the CS amplitude
      envelope increased. LFP power decreased in frequency bands other than 53.7 Hz. In
      the unpaired group, SSEPs did not change in the test compared with
      preconditioning. Our results show that AFC causes dissociated changes in the
      phase and power of SSEP in the IC.NEW & NOTEWORTHY Local field potential
      oscillations in the inferior colliculus follow the amplitude envelope of an
      amplitude-modulated tone, originating a neural response called the steady-state
      evoked potential. We show that auditory fear conditioning of an amplitude
      modulated tone modifies two parameters of the steady-state evoked potentials in
      the inferior colliculus: first the phase to which the evoked oscillation couples
      to the amplitude-modulated tone shifts; subsequently, the evoked oscillation
      power increases along with its coherence with the amplitude-modulated tone.

PMID- 28446583
TI  - A shared neural integrator for human posture control.
AB  - Control of standing posture requires fusion of multiple inputs including visual,
      vestibular, somatosensory, and other sensors, each having distinct dynamics. The
      semicircular canals, for example, have a unique high-pass filter response to
      angular velocity, quickly sensing a step change in head rotational velocity
      followed by a decay. To stabilize gaze direction despite this decay, the central
      nervous system supplies a neural "velocity storage" integrator, a filter that
      extends the angular velocity signal. Similar filtering might contribute temporal
      dynamics to posture control, as suggested by some state estimation models.
      However, such filtering has not been tested explicitly. We propose that posture
      control indeed entails a neural integrator for sensory inputs, and we test its
      behavior with classic sensory perturbations: a rotating optokinetic stimulus to
      the visual system and a galvanic vestibular stimulus to the vestibular system. A
      simple model illustrates how these two inputs and body tilt sensors might produce
      a postural tilt response in the frontal plane. The model integrates these signals
      through a direct weighted sum of inputs, with or without an indirect pathway
      containing a neural integrator. Comparison with experimental data from healthy
      adult subjects (N = 16) reveals that the direct weighting model alone is
      insufficient to explain resulting postural transients, as measured by lateral
      tilt of the trunk. In contrast, the neural integrator, shared by sensory signals,
      produces the dynamics of both optokinetic and galvanic vestibular responses.
      These results suggest that posture control may involve both direct and indirect
      pathways, which filter sensory signals and make them compatible for sensory
      fusion.NEW & NOTEWORTHY Control of standing posture requires fusion of multiple
      inputs including visual, vestibular, somatosensory, and other sensors, each
      having distinct dynamics. We propose that postural control also entails a shared
      neural integrator. To test this theory, we perturbed standing subjects with
      classic sensory stimuli (optokinetic and galvanic vestibular stimulation) and
      found that our proposed shared filter reproduces the dynamics of subjects'
      postural responses.

PMID- 28446584
TI  - Human primary somatosensory cortex is differentially involved in vibrotaction and
      nociception.
AB  - The role of the primary somatosensory cortex (S1) in vibrotaction is well
      established. In contrast, its involvement in nociception is still debated. Here
      we test whether S1 is similarly involved in the processing of nonnociceptive and
      nociceptive somatosensory input in humans by comparing the aftereffects of high
      definition transcranial direct current stimulation (HD-tDCS) of S1 on the event
      related potentials (ERPs) elicited by nonnociceptive and nociceptive
      somatosensory stimuli delivered to the ipsilateral and contralateral hands.
      Cathodal HD-tDCS significantly affected the responses to nonnociceptive
      somatosensory stimuli delivered to the contralateral hand: both early-latency
      ERPs from within S1 (N20 wave elicited by transcutaneous electrical stimulation
      of median nerve) and late-latency ERPs elicited outside S1 (N120 wave elicited by
      short-lasting mechanical vibrations delivered to index fingertip, thought to
      originate from bilateral operculo-insular and cingulate cortices). These results
      support the notion that S1 constitutes an obligatory relay for the cortical
      processing of nonnociceptive tactile input originating from the contralateral
      hemibody. Contrasting with this asymmetric effect of HD-tDCS on the responses to
      nonnociceptive somatosensory input, HD-tDCS over the sensorimotor cortex led to a
      bilateral and symmetric reduction of the magnitude of the N240 wave of
      nociceptive laser-evoked potentials elicited by stimulation of the hand dorsum.
      Taken together, our results demonstrate in humans a differential involvement of
      S1 in vibrotaction and nociception.NEW & NOTEWORTHY Whereas the role of the
      primary somatosensory cortex (S1) in vibrotaction is well established, its
      involvement in nociception remains strongly debated. By assessing, in healthy
      volunteers, the effect of high-definition transcranial direct current stimulation
      over S1, we demonstrate a differential involvement of S1 in vibrotaction and
      nociception.

PMID- 28446585
TI  - Activation mechanism of a neuromodulator-gated pacemaker ionic current.
AB  - The neuromodulator-gated current (IMI) found in the crab stomatogastric ganglion
      is activated by neuromodulators that are essential to induce the rhythmic
      activity of the pyloric network in this system. One of these neuromodulators is
      also known to control the correlated expression of voltage-gated ionic currents
      in pyloric neurons, as well as synaptic plasticity and strength. Thus
      understanding the mechanism by which neuromodulator receptors activate IMI should
      provide insights not only into how oscillations are initiated but also into how
      other processes, and currents not directly activated by them, are regulated. To
      determine what specific signaling molecules are implicated in this process, we
      used a battery of agonists and antagonists of common signal transduction
      pathways. We found that the G protein inhibitor GDPbetaS and the G protein
      activator GTPgammaS significantly affect IMI amplitude, suggesting that its
      activation is mediated by G proteins. Interestingly, when using the more specific
      G protein blocker pertussis toxin, we observed the expected inhibition of IMI
      amplitude but, unexpectedly, in a calcium-dependent fashion. We also found that
      antagonists of calcium- and calmodulin-associated signaling significantly reduce
      IMI amplitude. In contrast, we found little evidence for the role of cyclic
      nucleotide signaling, phospholipase C (PLC), or kinases and phosphatases, except
      two calmodulin-dependent kinases. In sum, these results suggest that proctolin
      induced IMI is mediated by a G protein whose pertussis toxin sensitivity is
      altered by external calcium concentration and appears to depend on intracellular
      calcium, calmodulin, and calmodulin-activated kinases. In contrast, we found no
      support for IMI being mediated by PLC signaling or cyclic nucleotides.NEW &
      NOTEWORTHY Neuronal rhythmic activity is generated by either network-based or
      cell-autonomous mechanisms. In the pyloric network of decapod crustaceans, the
      activation of a neuromodulator-gated pacemaker current is crucial for the
      generation of rhythmic activity. This current is activated by several
      neuromodulators, including peptides and acetylcholine, presumably via
      metabotropic receptors. We have previously demonstrated a novel extracellular
      calcium-sensitive voltage-dependence mechanism of this current. We presently
      report that the activation mechanism depends on intracellular and extracellular
      calcium-sensitive components.

PMID- 28446586
TI  - Muscle synergies obtained from comprehensive mapping of the primary motor cortex
      forelimb representation using high-frequency, long-duration ICMS.
AB  - Simplifying neuromuscular control for movement has previously been explored by
      extracting muscle synergies from voluntary movement electromyography (EMG)
      patterns. The purpose of this study was to investigate muscle synergies
      represented in EMG recordings associated with direct electrical stimulation of
      single sites in primary motor cortex (M1). We applied single-electrode high
      frequency, long-duration intracortical microstimulation (HFLD-ICMS) to the
      forelimb region of M1 in two rhesus macaques using parameters previously found to
      produce forelimb movements to stable spatial end points (90-150 Hz, 90-150 MUA,
      1,000-ms stimulus train lengths). To develop a comprehensive representation of
      cortical output, stimulation was applied systematically across the full extent of
      M1. We recorded EMG activity from 24 forelimb muscles together with movement
      kinematics. Nonnegative matrix factorization (NMF) was applied to the mean
      stimulus-evoked EMG, and the weighting coefficients associated with each synergy
      were mapped to the cortical location of the stimulating electrode. Synergies were
      found for three data sets including 1) all stimulated sites in the cortex, 2) a
      subset of sites that produced stable movement end points, and 3) EMG activity
      associated with voluntary reaching. Two or three synergies accounted for 90% of
      the overall variation in voluntary movement EMG whereas four or five synergies
      were needed for HFLD-ICMS-evoked EMG data sets. Maps of the weighting
      coefficients from the full HFLD-ICMS data set show limited regional areas of
      higher activation for particular synergies. Our results demonstrate fundamental
      NMF-based muscle synergies in the collective M1 output, but whether and how the
      central nervous system might coordinate movements using these synergies remains
      unclear.NEW & NOTEWORTHY While muscle synergies have been investigated in various
      muscle activity sets, it is unclear whether and how synergies may be organized in
      the cortex. We have investigated muscle synergies resulting from high-frequency,
      long-duration intracortical microstimulation (HFLD-ICMS) applied throughout M1.
      We compared HFLD-ICMS synergies to synergies from voluntary movement. While
      synergies can be identified from M1 stimulation, they are not clearly related to
      voluntary movement synergies and do not show an orderly topographic organization
      across M1.

PMID- 28446587
TI  - Temporal integration and 1/f power scaling in a circuit model of cerebellar
      interneurons.
AB  - Inhibitory interneurons interconnected via electrical and chemical (GABAA
      receptor) synapses form extensive circuits in several brain regions. They are
      thought to be involved in timing and synchronization through fast feedforward
      control of principal neurons. Theoretical studies have shown, however, that
      whereas self-inhibition does indeed reduce response duration, lateral inhibition,
      in contrast, may generate slow response components through a process of gradual
      disinhibition. Here we simulated a circuit of interneurons (stellate and basket
      cells) of the molecular layer of the cerebellar cortex and observed circuit time
      constants that could rise, depending on parameter values, to >1 s. The
      integration time scaled both with the strength of inhibition, vanishing
      completely when inhibition was blocked, and with the average connection distance,
      which determined the balance between lateral and self-inhibition. Electrical
      synapses could further enhance the integration time by limiting heterogeneity
      among the interneurons and by introducing a slow capacitive current. The model
      can explain several observations, such as the slow time course of OFF-beam
      inhibition, the phase lag of interneurons during vestibular rotation, or the
      phase lead of Purkinje cells. Interestingly, the interneuron spike trains
      displayed power that scaled approximately as 1/f at low frequencies. In
      conclusion, stellate and basket cells in cerebellar cortex, and interneuron
      circuits in general, may not only provide fast inhibition to principal cells but
      also act as temporal integrators that build a very short-term memory.NEW &
      NOTEWORTHY The most common function attributed to inhibitory interneurons is
      feedforward control of principal neurons. In many brain regions, however, the
      interneurons are densely interconnected via both chemical and electrical synapses
      but the function of this coupling is largely unknown. Based on large-scale
      simulations of an interneuron circuit of cerebellar cortex, we propose that this
      coupling enhances the integration time constant, and hence the memory trace, of
      the circuit.

PMID- 28446589
TI  - Antifibrotic effects of cyclosporine A on TGF-beta1-treated lung fibroblasts and
      lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1alpha.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is
      characterized by aberrant tissue remodeling and the formation of fibroblastic
      foci that are composed of fibrogenic myofibroblasts. TGF-beta1 is one of the
      factors that are responsible for fibrosis as it promotes fibroblast to
      myofibroblast differentiation (FMD) and is associated with up-regulation of alpha
      smooth muscle actin. Therefore, inhibition of FMD may represent an effective
      strategy for the treatment of IPF. Here, we describe the treatment of human lung
      fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF
      beta1-induced FMD via degradation of hypoxia-inducible factor-1alpha (HIF
      1alpha). In addition, in primary myofibroblast-like cells that were obtained from
      a patient with pulmonary fibrosis, treatment with CsA and an HIF-1alpha inhibitor
      (HIFi) decreased the expression levels of alpha-smooth muscle actin and
      fibronectin, which indicated that CsA and HIFi promote dedifferentiation of
      myofibroblasts. In mice intratracheally administered CsA or HIFi at an early
      fibrotic stage [7, 8, and 9 d postinstillation (dpi) of bleomycin], marked
      alleviation of lung fibrosis was observed at 14 dpi. These results suggest that
      CsA exhibits antifibrotic effects by degrading HIF-1alpha and that the CsA-HIF
      1alpha axis provides new insights into therapeutic options for the treatment of
      IPF.-Yamazaki, R., Kasuya, Y., Fujita, T., Umezawa, H., Yanagihara, M., Nakamura,
      H., Yoshino, I., Tatsumi, K., Murayama, T. Antifibrotic effects of cyclosporine A
      on TGF-beta1-treated lung fibroblasts and lungs from bleomycin-treated mice: role
      of hypoxia-inducible factor-1alpha.

PMID- 28446588
TI  - Hierarchical differences in population coding within auditory cortex.
AB  - Most models of auditory cortical (AC) population coding have focused on primary
      auditory cortex (A1). Thus our understanding of how neural coding for sounds
      progresses along the cortical hierarchy remains obscure. To illuminate this, we
      recorded from two AC fields: A1 and middle lateral belt (ML) of rhesus macaques.
      We presented amplitude-modulated (AM) noise during both passive listening and
      while the animals performed an AM detection task ("active" condition). In both
      fields, neurons exhibit monotonic AM-depth tuning, with A1 neurons mostly
      exhibiting increasing rate-depth functions and ML neurons approximately evenly
      distributed between increasing and decreasing functions. We measured noise
      correlation (rnoise) between simultaneously recorded neurons and found that
      whereas engagement decreased average rnoise in A1, engagement increased average
      rnoise in ML. This finding surprised us, because attentive states are commonly
      reported to decrease average rnoise We analyzed the effect of rnoise on AM coding
      in both A1 and ML and found that whereas engagement-related shifts in rnoise in
      A1 enhance AM coding, rnoise shifts in ML have little effect. These results imply
      that the effect of rnoise differs between sensory areas, based on the
      distribution of tuning properties among the neurons within each population. A
      possible explanation of this is that higher areas need to encode nonsensory
      variables (e.g., attention, choice, and motor preparation), which impart common
      noise, thus increasing rnoise Therefore, the hierarchical emergence of rnoise
      robust population coding (e.g., as we observed in ML) enhances the ability of
      sensory cortex to integrate cognitive and sensory information without a loss of
      sensory fidelity.NEW & NOTEWORTHY Prevailing models of population coding of
      sensory information are based on a limited subset of neural structures. An
      important and under-explored question in neuroscience is how distinct areas of
      sensory cortex differ in their population coding strategies. In this study, we
      compared population coding between primary and secondary auditory cortex. Our
      findings demonstrate striking differences between the two areas and highlight the
      importance of considering the diversity of neural structures as we develop models
      of population coding.

PMID- 28446590
TI  - Effects of RNA integrity on transcript quantification by total RNA sequencing of
      clinically collected human placental samples.
AB  - RNA degradation is a ubiquitous process that occurs in living and dead cells, as
      well as during handling and storage of extracted RNA. Reduced RNA quality caused
      by degradation is an established source of uncertainty for all RNA-based gene
      expression quantification techniques. RNA sequencing is an increasingly preferred
      method for transcriptome analyses, and dependence of its results on input RNA
      integrity is of significant practical importance. This study aimed to
      characterize the effects of varying input RNA integrity [estimated as RNA
      integrity number (RIN)] on transcript level estimates and delineate the
      characteristic differences between transcripts that differ in degradation rate.
      The study used ribodepleted total RNA sequencing data from a real-life clinically
      collected set (n = 32) of human solid tissue (placenta) samples. RIN-dependent
      alterations in gene expression profiles were quantified by using DESeq2 software.
      Our results indicate that small differences in RNA integrity affect gene
      expression quantification by introducing a moderate and pervasive bias in
      expression level estimates that significantly affected 8.1% of studied genes. The
      rapidly degrading transcript pool was enriched in pseudogenes, short noncoding
      RNAs, and transcripts with extended 3' untranslated regions. Typical slowly
      degrading transcripts (median length, 2389 nt) represented protein coding genes
      with 4-10 exons and high guanine-cytosine content.-Reiman, M., Laan, M., Rull,
      K., Sober, S. Effects of RNA integrity on transcript quantification by total RNA
      sequencing of clinically collected human placental samples.

PMID- 28446591
TI  - NFAT5-sensitive Orai1 expression and store-operated Ca2+ entry in megakaryocytes.
AB  - The transcription factor nuclear factor of activated T cells 5 (NFAT5) is up
      regulated in several clinical disorders, including dehydration. NFAT5-sensitive
      genes include serum and glucocorticoid-inducible kinase 1 (SGK1). The kinase is a
      powerful regulator of Orai1, a Ca2+ channel accomplishing store-operated Ca2+
      entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca2+
      sensors stromal interaction molecule 1 (STIM1), or STIM2, or both. In the present
      study, we explored whether nuclear factor of activated T cell (NFAT)-5 influences
      Ca2+ signaling in megakaryocytes. To this end, human megakaryocytic (MEG-01)
      cells were transfected with NFAT5 or with siNFAT5. Platelets and megakaryocytes
      were isolated from wild-type mice with either access to water ad libitum or
      dehydration by 36 h of water deprivation. Transcript levels were determined with
      quantitative RT-PCR and protein abundance by Western blot analysis and flow
      cytometry, cytosolic (intracellular) Ca2+ concentration ([Ca2+]i) by fura-2
      fluorescence. SOCE was estimated from the increase of [Ca2+]i following
      readdition of extracellular Ca2+ after store depletion with thapsigargin (1 uM).
      Platelet degranulation was estimated from P-selectin abundance and integrin
      activation from alphaIIbbeta3 integrin abundance determined by flow cytometry. As
      a result, NFAT5 transfection or exposure to hypertonicity (+40 mM NaCl) of MEG-01
      cells increased Orai1, Orai2, STIM1, and STIM2 transcript levels. Orai1
      transcript levels were decreased by NFAT5 silencing. NFAT5 transfection and
      IkappaB inhibitor BMS 345541 (5 uM) increased SOCE, whereas NFAT5 silencing and
      SGK1 inhibitor GSK650394 (10 uM) decreased SOCE. In the mice, dehydration
      increased NFAT5 and Orai1 protein abundance in megakaryocytes and NFAT5, Orai1,
      and Orai2 abundance in platelets. Dehydration further augmented the degranulation
      and integrin activation by thrombin and collagen-related peptide. In summary,
      NFAT5 is a powerful regulator of Orai1-expression and SOCE in megakaryocytes.
      Sahu, I., Pelzl, L., Sukkar, B., Fakhri, H., al-Maghout, T., Cao, H., Hauser, S.,
      Gutti, R., Gawaz, M., Lang, F. NFAT5-sensitive Orai1 expression and store
      operated Ca2+ entry in megakaryocytes.

PMID- 28446592
TI  - Bim gene dosage is critical in modulating nephron progenitor survival in the
      absence of microRNAs during kidney development.
AB  - Low nephron endowment at birth has been associated with an increased risk for
      developing hypertension and chronic kidney disease. We demonstrated in an earlier
      study that conditional deletion of the microRNA (miRNA)-processing enzyme Dicer
      from nephron progenitors results in premature depletion of the progenitors and
      increased expression of the proapoptotic protein Bim (also known as Bcl-2L11). In
      this study, we generated a compound mouse model with conditional deletion of both
      Dicer and Bim, to determine the biologic significance of increased Bim expression
      in Dicer-deficient nephron progenitors. The loss of Bim partially restored the
      number of nephron progenitors and improved nephron formation. The number of
      progenitors undergoing apoptosis was significantly reduced in kidneys with loss
      of a single allele, or both alleles, of Bim compared to mutant kidneys.
      Furthermore, 2 miRNAs expressed in nephron progenitors (miR-17 and miR-106b)
      regulated Bim levels in vitro and in vivo Together, these data suggest that miRNA
      mediated regulation of Bim controls nephron progenitor survival during
      nephrogenesis, as one potential means of regulating nephron endowment.-Cerqueira,
      D. M., Bodnar, A. J., Phua, Y. L., Freer, R., Hemker, S. L., Walensky, L. D.,
      Hukriede, N. A., Ho, J. Bim gene dosage is critical in modulating nephron
      progenitor survival in the absence of microRNAs during kidney development.

PMID- 28446593
TI  - Creating cell type-specific mutants by enhancer mutagenesis.
AB  - Cell signaling plays an essential role in development, and knowledge of the
      identities of the cells sending the signal is critical. This can be a challenge,
      since signaling pathways and ligands are commonly used at multiple times and in
      multiple cell types during development. One solution to this problem is to create
      cell type-specific mutants using CRISPR/Cas9 to mutate enhancers that control
      different patterns of expression. In this issue of Genes & Development, Rogers
      and colleagues (pp. 634-638) provide the first use of this method in Drosophila
      to solve a long-standing issue in patterning of the embryonic central nervous
      system.

PMID- 28446594
TI  - Pioneering EBF2 remodels the brown fat chromatin landscape.
AB  - In this issue of Genes & Development, Shapira and colleagues (pp. 660-673)
      outline mechanisms by which the brown fat transcription factor early B-cell
      factor 2 (EBF2) selectively activates brown lineage-specific gene expression. The
      investigators show that EBF2 interacts with and recruits a tissue-specific BAF
      chromatin remodeling complex to brown fat gene enhancers, thereby regulating
      chromatin accessibility. Their findings provide important insight into epigenetic
      regulation of adipocyte fate and thermogenic gene expression.

PMID- 28446595
TI  - DNA damage signaling mediates the functional antagonism between replicative
      senescence and terminal muscle differentiation.
AB  - The molecular determinants of muscle progenitor impairment to regenerate aged
      muscles are currently unclear. We show that, in a mouse model of replicative
      senescence, decline in muscle satellite cell-mediated regeneration coincides with
      activation of DNA damage response (DDR) and impaired ability to differentiate
      into myotubes. Inhibition of DDR restored satellite cell differentiation ability.
      Moreover, in replicative human senescent fibroblasts, DDR precluded MYOD-mediated
      activation of the myogenic program. A DDR-resistant MYOD mutant could overcome
      this barrier by resuming cell cycle progression. Likewise, DDR inhibition could
      also restore MYOD's ability to activate the myogenic program in human senescent
      fibroblasts. Of note, we found that cell cycle progression is necessary for the
      DDR-resistant MYOD mutant to reverse senescence-mediated inhibition of the
      myogenic program. These data provide the first evidence of DDR-mediated
      functional antagonism between senescence and MYOD-activated gene expression and
      indicate a previously unrecognized requirement of cell cycle progression for the
      activation of the myogenic program.

PMID- 28446596
TI  - Dicer loss and recovery induce an oncogenic switch driven by transcriptional
      activation of the oncofetal Imp1-3 family.
AB  - MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression
      critical for organismal viability. Changes in miRNA activity are common in
      cancer, but how these changes relate to subsequent alterations in transcription
      and the process of tumorigenesis is not well understood. Here, we report a deep
      transcriptional, oncogenic network regulated by miRNAs. We present analysis of
      the gene expression and phenotypic changes associated with global miRNA
      restoration in miRNA-deficient fibroblasts. This analysis uncovers a miRNA
      repressed network containing oncofetal genes Imp1, Imp2, and Imp3 (Imp1-3) that
      is up-regulated primarily transcriptionally >100-fold upon Dicer loss and is
      resistant to resilencing by complete restoration of miRNA activity. This Dicer
      resistant epigenetic switch confers tumorigenicity to these cells. Let-7 targets
      Imp1-3 are required for this tumorigenicity and feed back to reinforce and
      sustain expression of the oncogenic network. Together, these Dicer-resistant
      genes constitute an mRNA expression signature that is present in numerous human
      cancers and is associated with poor survival.

PMID- 28446597
TI  - The histone variant H2A.Z promotes splicing of weak introns.
AB  - Multiple lines of evidence implicate chromatin in the regulation of premessenger
      RNA (pre-mRNA) splicing. However, the influence of chromatin factors on
      cotranscriptional splice site usage remains unclear. Here we investigated the
      function of the highly conserved histone variant H2A.Z in pre-mRNA splicing using
      the intron-rich model yeast Schizosaccharomyces pombe Using epistatic miniarray
      profiles (EMAPs) to survey the genetic interaction landscape of the Swr1
      nucleosome remodeling complex, which deposits H2A.Z, we uncovered evidence for
      functional interactions with components of the spliceosome. In support of these
      genetic connections, splicing-specific microarrays show that H2A.Z and the Swr1
      ATPase are required during temperature stress for the efficient splicing of a
      subset of introns. Notably, affected introns are enriched for H2A.Z occupancy and
      more likely to contain nonconsensus splice sites. To test the significance of the
      latter correlation, we mutated the splice sites in an affected intron to
      consensus and found that this suppressed the requirement for H2A.Z in splicing of
      that intron. These data suggest that H2A.Z occupancy promotes cotranscriptional
      splicing of suboptimal introns that may otherwise be discarded via proofreading
      ATPases. Consistent with this model, we show that overexpression of splicing
      ATPase Prp16 suppresses both the growth and splicing defects seen in the absence
      of H2A.Z.

PMID- 28446599
TI  - Acute respiratory distress syndrome.
AB  - Since its first description, the acute respiratory distress syndrome (ARDS) has
      been acknowledged to be a major clinical problem in respiratory medicine. From
      July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This
      review summarises only eight of them as an arbitrary overview of clinical
      relevance: definition and epidemiology, risk factors, prevention and treatment. A
      strict application of definition criteria is crucial, but the diverse resource
      setting scenarios foster geographic variability and contrasting outcome data. A
      large international multicentre prospective cohort study including 50 countries
      across five continents reported that ARDS is underdiagnosed, and there is
      potential for improvement in its management. Furthermore, epidemiological data
      from low-income countries suggest that a revision of the current definition of
      ARDS is needed in order to improve its recognition and global clinical outcome.
      In addition to the well-known risk-factors for ARDS, exposure to high ozone
      levels and low vitamin D plasma concentrations were found to be predisposing
      circumstances. Drug-based preventive strategies remain a major challenge, since
      two recent trials on aspirin and statins failed to reduce the incidence in at
      risk patients. A new disease-modifying therapy is awaited: some recent studies
      promised to improve the prognosis of ARDS, but mortality and disabling
      complications are still high in survivors in intensive care.

PMID- 28446598
TI  - The histone variant H2A.Z promotes efficient cotranscriptional splicing in S.
      cerevisiae.
AB  - In eukaryotes, a dynamic ribonucleic protein machine known as the spliceosome
      catalyzes the removal of introns from premessenger RNA (pre-mRNA). Recent studies
      show the processes of RNA synthesis and RNA processing to be spatio-temporally
      coordinated, indicating that RNA splicing takes place in the context of
      chromatin. H2A.Z is a highly conserved histone variant of the canonical histone
      H2A. In Saccharomyces cerevisiae, H2A.Z is deposited into chromatin by the SWR-C
      complex, is found near the 5' ends of protein-coding genes, and has been
      implicated in transcription regulation. Here we show that splicing of intron
      containing genes in cells lacking H2A.Z is impaired, particularly under
      suboptimal splicing conditions. Cells lacking H2A.Z are especially dependent on a
      functional U2 snRNP (small nuclear RNA [snRNA] plus associated proteins), as
      H2A.Z shows extensive genetic interactions with U2 snRNP-associated proteins, and
      RNA sequencing (RNA-seq) reveals that introns with nonconsensus branch points are
      particularly sensitive to H2A.Z loss. Consistently, H2A.Z promotes efficient
      spliceosomal rearrangements involving the U2 snRNP, as H2A.Z loss results in
      persistent U2 snRNP association and decreased recruitment of downstream snRNPs to
      nascent RNA. H2A.Z impairs transcription elongation, suggesting that spliceosome
      rearrangements are tied to H2A.Z's role in elongation. Depletion of disassembly
      factor Prp43 suppresses H2A.Z-mediated splice defects, indicating that, in the
      absence of H2A.Z, stalled spliceosomes are disassembled, and unspliced RNAs are
      released. Together, these data demonstrate that H2A.Z is required for efficient
      pre-mRNA splicing and indicate a role for H2A.Z in coordinating the kinetics of
      transcription elongation and splicing.

PMID- 28446600
TI  - Management of suspected monogenic lung fibrosis in a specialised centre.
AB  - At least 10% of patients with interstitial lung disease present monogenic lung
      fibrosis suspected on familial aggregation of pulmonary fibrosis, specific
      syndromes or early age of diagnosis. Approximately 25% of families have an
      identified mutation in genes mostly involved in telomere homeostasis, and more
      rarely in surfactant homeostasis.Beyond pathophysiological knowledge, detection
      of these mutations has practical consequence for patients. For instance,
      mutations involved in telomere homeostasis are associated with haematological
      complications after lung transplantation and may require adapted
      immunosuppression. Moreover, relatives may benefit from a clinical and genetic
      evaluation that should be specifically managed.The field of genetics of pulmonary
      fibrosis has made great progress in the last 10 years, raising specific problems
      that should be addressed by a specialised team.

PMID- 28446601
TI  - Diffuse parenchymal lung disease.
AB  - Between September 2015 and August 2016 there were >1500 publications in the field
      of diffuse parenchymal lung diseases (DPLDs). For the Clinical Year in Review
      session at the European Respiratory Society Congress that was held in London, UK,
      in September 2016, we selected only five articles. This selection, made from the
      enormous number of published papers, does not include all the relevant studies
      that will significantly impact our knowledge in the field of DPLDs in the near
      future. This review article provides our personal view on the following topics:
      early diagnosis of idiopathic pulmonary fibrosis, current knowledge on the
      multidisciplinary team diagnosis of DPLDs and the diagnostic role of
      transbronchial cryobiopsy in this diagnostic setting, insights on the new entity
      of interstitial pneumonia with autoimmune features, and new therapeutic
      approaches for scleroderma-related interstitial lung disease.

PMID- 28446602
TI  - The TMEM106B risk allele is associated with lower cortical volumes in a
      clinically diagnosed frontotemporal dementia cohort.

PMID- 28446603
TI  - Levels of nitric oxide metabolites in cerebrospinal fluid correlate with
      cognitive impairment in early stage multiple sclerosis.

PMID- 28446605
TI  - CRISPR/Cas9-mediated gene knockout screens and target identification via whole
      genome sequencing uncover host genes required for picornavirus infection.
AB  - Several groups have used genome-wide libraries of lentiviruses encoding small
      guide RNAs (sgRNAs) for genetic screens. In most cases, sgRNA expression
      cassettes are integrated into cells by using lentiviruses, and target genes are
      statistically estimated by the readout of sgRNA sequences after targeted
      sequencing. We present a new virus-free method for human gene knockout screens
      using a genome-wide library of CRISPR/Cas9 sgRNAs based on plasmids and target
      gene identification via whole-genome sequencing (WGS) confirmation of authentic
      mutations rather than statistical estimation through targeted amplicon
      sequencing. We used 30,840 pairs of individually synthesized oligonucleotides to
      construct the genome-scale sgRNA library, collectively targeting 10,280 human
      genes (i.e. three sgRNAs per gene). These plasmid libraries were co-transfected
      with a Cas9-expression plasmid into human cells, which were then treated with
      cytotoxic drugs or viruses. Only cells lacking key factors essential for
      cytotoxic drug metabolism or viral infection were able to survive. Genomic DNA
      isolated from cells that survived these challenges was subjected to WGS to
      directly identify CRISPR/Cas9-mediated causal mutations essential for cell
      survival. With this approach, we were able to identify known and novel genes
      essential for viral infection in human cells. We propose that genome-wide sgRNA
      screens based on plasmids coupled with WGS are powerful tools for forward
      genetics studies and drug target discovery.

PMID- 28446604
TI  - Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and
      regulatory subunit 3B.
AB  - Greatwall (Gwl) kinase plays an essential role in the regulation of mitotic entry
      and progression. Mitotic activation of Gwl requires both cyclin-dependent kinase
      1 (CDK1)-dependent phosphorylation and its autophosphorylation at an
      evolutionarily conserved serine residue near the carboxyl terminus (Ser-883 in
      Xenopus). In this study we show that Gwl associates with protein phosphatase 1
      (PP1), particularly PP1gamma, which mediates the dephosphorylation of Gwl Ser
      883. Consistent with the mitotic activation of Gwl, its association with PP1 is
      disrupted in mitotic cells and egg extracts. During mitotic exit, PP1-dependent
      dephosphorylation of Gwl Ser-883 occurs prior to dephosphorylation of other
      mitotic substrates; replacing endogenous Gwl with a phosphomimetic S883E mutant
      blocks mitotic exit. Moreover, we identified PP1 regulatory subunit 3B (PPP1R3B)
      as a targeting subunit that can direct PP1 activity toward Gwl. PPP1R3B bridges
      PP1 and Gwl association and promotes Gwl Ser-883 dephosphorylation. Consistent
      with the cell cycle-dependent association of Gwl and PP1, Gwl and PPP1R3B
      dissociate in M phase. Interestingly, up-regulation of PPP1R3B facilitates
      mitotic exit and blocks mitotic entry. Thus, our study suggests PPP1R3B as a new
      cell cycle regulator that functions by governing Gwl dephosphorylation.

PMID- 28446606
TI  - The Behcet's disease-associated variant of the aminopeptidase ERAP1 shapes a low
      affinity HLA-B*51 peptidome by differential subpeptidome processing.
AB  - A low-activity variant of endoplasmic reticulum aminopeptidase 1 (ERAP1), Hap10,
      is associated with the autoinflammatory disorder Behcet's disease (BD) in
      epistasis with HLA-B*51, which is the main risk factor for this disorder. The
      role of Hap10 in BD pathogenesis is unknown. We sought to define the effects of
      Hap10 on the HLA-B*51 peptidome and to distinguish these effects from those due
      to HLA-B*51 polymorphisms unrelated to disease. The peptidome of the BD
      associated HLA-B*51:08 subtype expressed in a Hap10-positive cell line was
      isolated, characterized by mass spectrometry, and compared with the HLA-B*51:01
      peptidome from cells expressing more active ERAP1 allotypes. We additionally
      performed synthetic peptide digestions with recombinant ERAP1 variants and
      estimated peptide-binding affinity with standard algorithms. In the BD-associated
      ERAP1 context of B*51:08, longer peptides were generated; of the two major HLA
      B*51 subpeptidomes with Pro-2 and Ala-2, the former one was significantly
      reduced, and the latter was increased and showed more ERAP1-susceptible N
      terminal residues. These effects were readily explained by the low activity of
      Hap10 and the differential susceptibility of X-Pro and X-Ala bonds to ERAP1
      trimming and together resulted in a significantly altered peptidome with lower
      affinity. The differences due to ERAP1 were clearly distinguished from those due
      to HLA-B*51 subtype polymorphism, which affected residue frequencies at internal
      positions of the peptide ligands. The alterations in the nature and affinity of
      HLA-B*51.peptide complexes probably affect T-cell and natural killer cell
      recognition, providing a sound basis for the joint association of ERAP1 and HLA
      B*51 with BD.

PMID- 28446607
TI  - Juvenile hormone and its receptor methoprene-tolerant promote ribosomal
      biogenesis and vitellogenesis in the Aedes aegypti mosquito.
AB  - Juvenile hormone (JH) controls many biological activities in insects, including
      development, metamorphosis, and reproduction. In the Aedes aegypti mosquito, a
      vector of dengue, yellow fever, chikungunya, and zika viruses, the metabolic
      tissue (the fat body, which is an analogue of the vertebrate liver) produces yolk
      proteins for developing oocytes. JH is important for the fat body to acquire
      competence for yolk protein production. However, the molecular mechanisms of how
      JH promotes mosquito reproduction are not completely understood. In this study we
      show that stimulation of the JH receptor methoprene-tolerant (Met) activates
      expression of genes encoding the regulator of ribosome synthesis 1 (RRS1) and six
      ribosomal proteins (two ribosomal large subunit proteins, two ribosomal small
      subunit proteins, and two mitochondrial ribosomal proteins). Moreover, RNAi
      mediated depletion of RRS1 decreased biosynthesis of the ribosomal protein L32
      (RpL32). Depletion of Met, RRS1, or RpL32 led to retardation of ovarian growth
      and reduced mosquito fecundity, which may at least in part have resulted from
      decreased vitellogenin protein production in the fat body. In summary, our
      results indicate that JH is critical for inducing the expression of ribosomal
      protein genes and demonstrate that RRS1 mediates the JH signal to enhance both
      ribosomal biogenesis and vitellogenesis.

PMID- 28446608
TI  - Model-enabled gene search (MEGS) allows fast and direct discovery of enzymatic
      and transport gene functions in the marine bacterium Vibrio fischeri.
AB  - Whereas genomes can be rapidly sequenced, the functions of many genes are
      incompletely or erroneously annotated because of a lack of experimental evidence
      or prior functional knowledge in sequence databases. To address this weakness, we
      describe here a model-enabled gene search (MEGS) approach that (i) identifies
      metabolic functions either missing from an organism's genome annotation or
      incorrectly assigned to an ORF by using discrepancies between metabolic model
      predictions and experimental culturing data; (ii) designs functional selection
      experiments for these specific metabolic functions; and (iii) selects a candidate
      gene(s) responsible for these functions from a genomic library and directly
      interrogates this gene's function experimentally. To discover gene functions,
      MEGS uses genomic functional selections instead of relying on correlations across
      large experimental datasets or sequence similarity as do other approaches. When
      applied to the bioluminescent marine bacterium Vibrio fischeri, MEGS successfully
      identified five genes that are responsible for four metabolic and transport
      reactions whose absence from a draft metabolic model of V. fischeri caused
      inaccurate modeling of high-throughput experimental data. This work demonstrates
      that MEGS provides a rapid and efficient integrated computational and
      experimental approach for annotating metabolic genes, including those that have
      previously been uncharacterized or misannotated.

PMID- 28446610
TI  - Conformational changes at cytoplasmic intersubunit interactions control Kir
      channel gating.
AB  - The defining structural feature of inward-rectifier potassium (Kir) channels is
      the unique Kir cytoplasmic domain. Recently we showed that salt bridges located
      at the cytoplasmic domain subunit interfaces (CD-Is) of eukaryotic Kir channels
      control channel gating via stability of a novel inactivated closed state. The
      cytoplasmic domains of prokaryotic and eukaryotic Kir channels show similar
      conformational rearrangements to the common gating ligand, phosphatidylinositol
      bisphosphate (PIP2), although these exhibit opposite coupling to opening and
      closing transitions. In Kir2.1, mutation of one of these CD-I salt bridge
      residues (R204A) reduces apparent PIP2 sensitivity of channel activity, and here
      we show that Ala or Cys substitutions of the functionally equivalent residue (Arg
      165) in the prokaryotic Kir channel KirBac1.1 also significantly decrease
      sensitivity of the channel to PIP2 (by 5-30-fold). To further understand the
      structural basis of CD-I control of Kir channel gating, we examined the effect of
      the R165A mutation on PIP2-induced changes in channel function and conformation.
      Single-channel analyses indicated that the R165A mutation disrupts the
      characteristic long interburst closed state of reconstituted KirBac1.1 in giant
      liposomes, resulting in a higher open probability due to more frequent opening
      bursts. Intramolecular FRET measurements indicate that, relative to wild-type
      channels, the R165A mutation results in splaying of the cytoplasmic domains away
      from the central axis and that PIP2 essentially induces opposite motions of the
      major beta-sheet in this channel mutant. We conclude that the removal of
      stabilizing CD-I salt bridges results in a collapsed state of the Kir domain.

PMID- 28446609
TI  - Glycosylation of the core of the HIV-1 envelope subunit protein gp120 is not
      required for native trimer formation or viral infectivity.
AB  - The gp120 subunit of the HIV-1 envelope (Env) protein is heavily glycosylated at
      ~25 glycosylation sites, of which ~7-8 are located in the V1/V2 and V3 variable
      loops and the others in the remaining core gp120 region. Glycans partially shield
      Env from recognition by the host immune system and also are believed to be
      indispensable for proper folding of gp120 and for viral infectivity. Previous
      attempts to alter glycosylation sites in Env typically involved mutating the
      glycosylated asparagine residues to structurally similar glutamines or alanines.
      Here, we confirmed that such mutations at multiple glycosylation sites greatly
      diminish viral infectivity and result in significantly reduced binding to both
      neutralizing and non-neutralizing antibodies. Therefore, using an alternative
      approach, we combined evolutionary information with structure-guided design and
      yeast surface display to produce properly cleaved HIV-1 Env variants that lack
      all 15 core gp120 glycans, yet retain conformational integrity and multiple-cycle
      viral infectivity and bind to several broadly neutralizing antibodies (bNAbs),
      including trimer-specific antibodies and a germline-reverted version of the bNAb
      VRC01. Our observations demonstrate that core gp120 glycans are not essential for
      folding, and hence their likely primary role is enabling immune evasion. We also
      show that our glycan removal approach is not strain restricted. Glycan-deficient
      Env derivatives can be used as priming immunogens because they should engage and
      activate a more divergent set of germlines than fully glycosylated Env. In
      conclusion, these results clarify the role of core gp120 glycosylation and
      illustrate a general method for designing glycan-free folded protein derivatives.

PMID- 28446611
TI  - Unraveling amino acid residues critical for allosteric potentiation of
      (alpha4)3(beta2)2-type nicotinic acetylcholine receptor responses.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are promising drug targets to
      manage several neurological disorders and nicotine addiction. Growing evidence
      indicates that positive allosteric modulators of nAChRs improve pharmacological
      specificity by binding to unique sites present only in a subpopulation of nAChRs.
      Furthermore, nAChR positive allosteric modulators such as NS9283 and CMPI have
      been shown to potentiate responses of (alpha4)3(beta2)2 but not (alpha4)2(beta2)3
      nAChR isoforms. This selective potentiation underlines that the alpha4:alpha4
      interface, which is present only in the (alpha4)3(beta2)2 nAChR, is an important
      and promising drug target. In this report we used site-directed mutagenesis to
      substitute specific amino acid residues and computational analyses to elucidate
      CMPI's binding mode at the alpha4:alpha4 subunit extracellular interface and
      identified a unique set of amino acid residues that determined its affinity. We
      found that amino acid residues alpha4Gly-41, alpha4Lys-64, and alpha4Thr-66 were
      critical for (alpha4)3(beta2)2 nAChR potentiation by CMPI, but not by NS9283,
      whereas amino acid substitution at alpha4His-116, a known determinant of NS9283
      and of agonist binding at the alpha4:alpha4 subunit interface, did not reduce
      CMPI potentiation. In contrast, substitutions at alpha4Gln-124 and alpha4Thr-126
      reduced potentiation by CMPI and NS9283, indicating that their binding sites
      partially overlap. These results delineate the role of amino acid residues
      contributing to the alpha4:alpha4 subunit extracellular interface in nAChR
      potentiation. These findings also provide structural information that will
      facilitate the structure-based design of novel therapeutics that target
      selectively the (alpha4)3(beta2)2 nAChR.

PMID- 28446612
TI  - CDK4 protein is degraded by anaphase-promoting complex/cyclosome in mitosis and
      reaccumulates in early G1 phase to initiate a new cell cycle in HeLa cells.
AB  - CDK4 regulates G1/S phase transition in the mammalian cell cycle by
      phosphorylating retinoblastoma family proteins. However, the mechanism underlying
      the regulation of CDK4 activity is not fully understood. Here, we show that CDK4
      protein is degraded by anaphase-promoting complex/cyclosome (APC/C) during
      metaphase-anaphase transition in HeLa cells, whereas its main regulator, cyclin
      D1, remains intact but is sequestered in cytoplasm. CDK4 protein reaccumulates in
      the following G1 phase and shuttles between the nucleus and the cytoplasm to
      facilitate the nuclear import of cyclin D1. Without CDK4, cyclin D1 cannot enter
      the nucleus. Point mutations that disrupt CDK4 and cyclin D1 interaction impair
      the nuclear import of cyclin D1 and the activity of CDK4. RNAi knockdown of CDK4
      also induces cytoplasmic retention of cyclin D1 and G0/G1 phase arrest of the
      cells. Collectively, our data demonstrate that CDK4 protein is degraded in late
      mitosis and reaccumulates in the following G1 phase to facilitate the nuclear
      import of cyclin D1 for activation of CKD4 to initiate a new cell cycle in HeLa
      cells.

PMID- 28446613
TI  - Structural basis for ligand capture and release by the endocytic receptor ApoER2.
AB  - Apolipoprotein E receptor 2 (ApoER2) is a close homologue of low-density
      lipoprotein receptor (LDLR) that mediates the endocytosis of ligands, including
      LDL particles. LDLR family members have been presumed to explore a large
      conformational space to capture ligands in the extended conformation at the cell
      surface. Ligands are subsequently released through a pH-titrated structural
      transition to a self-docked, contracted-closed conformation. In addition to
      lipoprotein uptake, ApoER2 is implicated in signal transduction during brain
      development through capture of the extracellular protein reelin. From
      crystallographic analysis, we determine that the full-length ApoER2 ectodomain
      adopts an intermediate contracted-open conformation when complexed with the
      signaling-competent reelin fragment, and we identify a previously unappreciated
      auxiliary low-affinity binding interface. Based on mutational analyses, we
      propose that the pH shift during endocytosis weakens the affinity of the
      auxiliary interface and destabilizes the ligand-receptor complex. Furthermore,
      this study elucidates that the contracted-open conformation of ligand-bound
      ApoER2 at neutral pH resembles the contracted-closed conformation of ligand
      unbound LDLR at acidic pH in a manner suggestive of being primed for ligand
      release even prior to internalization.

PMID- 28446614
TI  - Constraining the instantaneous aerosol influence on cloud albedo.
AB  - Much of the uncertainty in estimates of the anthropogenic forcing of climate
      change comes from uncertainties in the instantaneous effect of aerosols on cloud
      albedo, known as the Twomey effect or the radiative forcing from aerosol-cloud
      interactions (RFaci), a component of the total or effective radiative forcing.
      Because aerosols serving as cloud condensation nuclei can have a strong influence
      on the cloud droplet number concentration (Nd ), previous studies have used the
      sensitivity of the Nd to aerosol properties as a constraint on the strength of
      the RFaci. However, recent studies have suggested that relationships between
      aerosol and cloud properties in the present-day climate may not be suitable for
      determining the sensitivity of the Nd to anthropogenic aerosol perturbations.
      Using an ensemble of global aerosol-climate models, this study demonstrates how
      joint histograms between Nd and aerosol properties can account for many of the
      issues raised by previous studies. It shows that if the anthropogenic
      contribution to the aerosol is known, the RFaci can be diagnosed to within 20% of
      its actual value. The accuracy of different aerosol proxies for diagnosing the
      RFaci is investigated, confirming that using the aerosol optical depth
      significantly underestimates the strength of the aerosol-cloud interactions in
      satellite data.

PMID- 28446615
TI  - Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted
      therapy in lung cancer patients.
AB  - Exhausted T cells in chronic infections and cancer have sustained expression of
      the inhibitory receptor programmed cell death 1 (PD-1). Therapies that block the
      PD-1 pathway have shown promising clinical results in a significant number of
      advanced-stage cancer patients. Nonetheless, a better understanding of the
      immunological responses induced by PD-1 blockade in cancer patients is lacking.
      Identification of predictive biomarkers is a priority in the field, but whether
      peripheral blood analysis can provide biomarkers to monitor or predict patients'
      responses to treatment remains to be resolved. In this study, we analyzed
      longitudinal blood samples from advanced stage non-small cell lung cancer (NSCLC)
      patients (n = 29) receiving PD-1-targeted therapies. We detected an increase in
      Ki-67+ PD-1+ CD8 T cells following therapy in ~70% of patients, and most
      responses were induced after the first or second treatment cycle. This T-cell
      activation was not indiscriminate because we observed only minimal effects on EBV
      specific CD8 T cells, suggesting that responding cells may be tumor specific.
      These proliferating CD8 T cells had an effector-like phenotype (HLA-DR+, CD38+,
      Bcl-2lo), expressed costimulatory molecules (CD28, CD27, ICOS), and had high
      levels of PD-1 and coexpression of CTLA-4. We found that 70% of patients with
      disease progression had either a delayed or absent PD-1+ CD8 T-cell response,
      whereas 80% of patients with clinical benefit exhibited PD-1+ CD8 T-cell
      responses within 4 wk of treatment initiation. Our results suggest that
      peripheral blood analysis may provide valuable insights into NSCLC patients'
      responses to PD-1-targeted therapies.

PMID- 28446617
TI  - Is embryonic hypothermia tolerance common in birds?
AB  - Avian incubation temperatures oscillate within narrow limits to ensure proper
      embryonic development. However, field observations and experimental studies have
      found that some species can tolerate very low incubation temperatures, either
      regularly or occasionally. We artificially incubated eggs from five domestic
      species, which represent a range of egg sizes, to examine whether a diversity of
      avian species could exhibit an unusual hypothermia tolerance, as observed in the
      field. We found that eggs of the chicken (Gallus gallus domesticus), pigeon
      (Columba livia domestica), Japanese quail (Coturnix japonica) and budgerigar
      (Melopsittacus undulatus) survived the incubation period and hatched after
      experiencing 10 degrees C hypothermia for 6 h each day. However, embryos of white
      rumped munia (Lonchura striata) died after 10 days of hypothermia. Our results
      showed that unusual hypothermia tolerance occurs in several avian species. This
      phenomenon might have been selected through the evolutionary history of birds.
      Future research should identify the importance of phylogeny, egg size and
      embryonic stage in tolerance to hypothermia.

PMID- 28446618
TI  - The role of feeding morphology and competition in governing the diet breadth of
      sympatric stomatopod crustaceans.
AB  - Competition for food drives divergence and specialization in feeding morphology.
      Stomatopod crustaceans have two kinds of highly specialized feeding appendages:
      either elongate spear-like appendages (spearers) used to ambush soft-bodied
      evasive prey or hammer-like appendages (smashers) that produce extremely high
      forces used both to break hard-shelled prey and to capture evasive prey. To
      evaluate associations between appendage type and feeding ecology, the diet of two
      small smasher and spearer species (size range: 21-27 mm) that co-occur were
      compared. Stable isotope analysis and the Bayesian mixing model MixSIAR were used
      to estimate the proportional contributions of prey types to the diet. Both
      species had relatively wide diets that included hard-shelled and soft-bodied
      prey, albeit in different proportions; the smasher consumed a greater proportion
      of hard-shelled prey, and the spearer consumed mostly soft-bodied prey. Appendage
      kinematics in stomatopods is known to scale linearly across species. These two
      small species may produce similar kinematics allowing them both to capture
      evasive prey and hammer hard-shelled prey, thereby widening their diets. Yet, the
      spearer species is more highly adept at capturing evasive prey, indicating that
      small spearers are stronger competitors for soft-bodied prey. These findings
      suggest that a smasher's ability to access hard prey reduced competition for soft
      prey, and therefore conferred an important benefit favouring the evolution of the
      impressive smashing strike.

PMID- 28446616
TI  - Early immune responses are independent of RGC dysfunction in glaucoma with
      complement component C3 being protective.
AB  - Various immune response pathways are altered during early, predegenerative stages
      of glaucoma; however, whether the early immune responses occur secondarily to or
      independently of neuronal dysfunction is unclear. To investigate this
      relationship, we used the Wlds allele, which protects from axon dysfunction. We
      demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are
      protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes
      that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are
      still altered in DBA/2J.Wlds mice. This suggests that immune changes are not
      secondary to RGC dysfunction or altered neuroglial interactions, but may be
      directly induced by the increased strain imposed by high IOP. One early immune
      response following IOP elevation is up-regulation of complement C3 in astrocytes
      of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other
      complement components, such as C1Q, is protective in glaucoma, C3 deficiency
      significantly increased the number of DBA/2J eyes with nerve damage and RGC loss
      at an early time point after IOP elevation. Transcriptional profiling of C3
      deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent
      responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased
      the number of DBA/2J eyes with glaucoma at the same early time point. These
      findings suggest that C3 protects from early glaucomatous damage, a process that
      may involve EGFR signaling and other immune responses in the optic nerve head.
      Therefore, therapies that target specific components of the complement cascade,
      rather than global inhibition, may be more applicable for treating human
      glaucoma.

PMID- 28446619
TI  - Candidate genes mediating magnetoreception in rainbow trout (Oncorhynchus
      mykiss).
AB  - Diverse animals use Earth's magnetic field in orientation and navigation, but
      little is known about the molecular mechanisms that underlie magnetoreception.
      Recent studies have focused on two possibilities: (i) magnetite-based receptors;
      and (ii) biochemical reactions involving radical pairs. We used RNA sequencing to
      examine gene expression in the brain of rainbow trout (Oncorhynchus mykiss) after
      exposure to a magnetic pulse known to disrupt magnetic orientation behaviour. We
      identified 181 differentially expressed genes, including increased expression of
      six copies of the frim gene, which encodes a subunit of the universal iron
      binding and trafficking protein ferritin. Functions linked to the oxidative
      effects of free iron (e.g. oxidoreductase activity, transition metal ion binding,
      mitochondrial oxidative phosphorylation) were also affected. These results are
      consistent with the hypothesis that a magnetic pulse alters or damages magnetite
      based receptors and/or other iron-containing structures, which are subsequently
      repaired or replaced through processes involving ferritin. Additionally, some
      genes that function in the development and repair of photoreceptive structures
      (e.g. crggm3, purp, prl, gcip, crabp1 and pax6) were also differentially
      expressed, raising the possibility that a magnetic pulse might affect structures
      and processes unrelated to magnetite-based magnetoreceptors.

PMID- 28446620
TI  - How to win the HIV-1 drug resistance hurdle race: running faster or jumping
      higher?
AB  - Infections by the human immunodeficiency virus type 1 (HIV-1), the causative
      agent of the acquired immunodeficiency syndrome (AIDS), are still totaling an
      appalling 36.7 millions worldwide, with 1.1 million AIDS deaths/year and a
      similar number of yearly new infections. All this, in spite of the discovery of
      HIV-1 as the AIDS etiological agent more than 30 years ago and the introduction
      of an effective combinatorial antiretroviral therapy (cART), able to control
      disease progression, more than 20 years ago. Although very effective, current
      cART is plagued by the emergence of drug-resistant viral variants and most of the
      efforts in the development of novel direct-acting antiviral agents (DAAs) against
      HIV-1 have been devoted toward the fighting of resistance. In this review, rather
      than providing a detailed listing of all the drugs and the corresponding
      resistance mutations, we aim, through relevant examples, at presenting to the
      general reader the conceptual shift in the approaches that are being taken to
      overcome the viral resistance hurdle. From the classic 'running faster' strategy,
      based on the development of novel DAAs active against the mutant viruses selected
      by the previous drugs and/or presenting to the virus a high genetic barrier
      toward the development of resilience, to a 'jumping higher' approach, which looks
      at the cell, rather than the virus, as a source of valuable drug targets, in
      order to make the cellular environment non-permissive toward the replication of
      both wild-type and mutated viruses.

PMID- 28446621
TI  - Ischemic Stroke in Nonvalvular Atrial Fibrillation at Warfarin Initiation:
      Assessment via a Large Insurance Database.
AB  - BACKGROUND AND PURPOSE: Stroke risk may increase shortly after warfarin
      initiation in nonvalvular atrial fibrillation patients. Because of the brief
      period and limited number of events, large samples are needed to study this
      effect. We compared 30-day rates of ischemic stroke between nonvalvular atrial
      fibrillation patients initiating warfarin to nonwarfarin comparators using an
      insurance claims database. METHODS: We identified nonvalvular atrial fibrillation
      patients via 1 inpatient/2 outpatient diagnosis claims from the MarketScan
      database, January 1, 2009, to December 31, 2010. We studied patients initiating
      warfarin using prescription claims and 1:1 matched 22 669 initiators to
      comparators based on age, sex, diagnosis date, and warfarin propensity score.
      Follow-up began on initiation date; patients were censored at
      discontinuation/switch of therapy, disenrollment, or end of the study. The median
      follow-up was 415 days. Cox regression was used to study differences in ischemic
      stroke risks between warfarin initiators and comparators while controlling for
      important prognostic factors. RESULTS: Warfarin initiators were generally similar
      to comparators in clinical features but had higher CHADS2 scores (1.26 versus
      1.19). The first 30-day ischemic stroke rate was higher among warfarin initiators
      than comparators (1.47%/y (27/1836) versus 0.98%/y (18/1837); P=0.18) but lower
      subsequently (0.81%/y [134/16 543] versus 1.09%/y [406/37 248]; P=0.002).
      Multivariable regression confirmed a significant interaction between follow-up
      and warfarin use with the adjusted hazard ratios (95% confidence intervals) for
      warfarin/comparator as 1.46 (0.80-2.65) in the first 30 days and 0.70 (0.57-0.85)
      afterward. CONCLUSIONS: Warfarin effect was qualitatively different in the first
      30 days after initiation than subsequently. This is consistent with a modest
      increase in stroke risk occurring briefly after starting warfarin.

PMID- 28446622
TI  - Cortical Venous Redness Represents Tissue Circulation Status in Patients With
      Moyamoya Disease.
AB  - BACKGROUND AND PURPOSE: Venous oxygen saturation (SO2) is measured in medical
      fields to assess tissue circulation insufficiency. This study aimed to elucidate
      the use of a cortical venous redness measurement to evaluate hemodynamic changes
      during revascularization surgery for patients with moyamoya disease. METHODS: In
      this retrospective case-series analysis, we first quantitatively measured and
      correlated SO2 and R intensity of 24-bit color digital red-green-blue pictures of
      blood samples from 3 volunteers. Subsequently, based on intraoperative digital
      pictures of 29 patients with moyamoya disease, we measured the R intensities of a
      cortical vein near the anastomosis site before and after anastomosis. Cerebral
      blood flow (CBF) at the site was measured using a single-photon emission computed
      tomography before and 1 to 3 days after surgery. Venous R intensity and CBF were
      measured twice by 4 raters, and their correlations were examined using
      generalized linear mixed effect model and linear regression analysis. RESULTS: A
      strong linear correlation was found between blood R intensity and its SO2
      (coefficients, 0.522; 95% confidence interval, 0.364-0.680, using generalized
      linear mixed effect model). Venous R intensity before the anastomosis was not
      correlated with preoperative CBF (coefficients, 0.000352; 95% confidence
      interval, -0.000369 to 0.00107, by generalized linear mixed effect); however, the
      increases in venous R intensity after anastomosis were correlated with
      postoperative increases in CBF (R2, 0.367; 95% confidence interval, 0.116-0.618
      to 0.548; 95% confidence interval, 0.331-0.764, by linear regression analysis).
      CONCLUSIONS: Cortical venous redness represented impaired CBF and could be a
      useful parameter for assessing hemodynamic changes during revascularization
      surgery.

PMID- 28446623
TI  - Letter by Nighoghossian Regarding Article, "Risk of Pulmonary Embolism After
      Cerebral Venous Thrombosis".

PMID- 28446624
TI  - Response by Merkler et al to Letter Regarding Article, "Risk of Pulmonary
      Embolism After Cerebral Venous Thrombosis".

PMID- 28446626
TI  - Faith and loss: masterpieces from the Middlesex Hospital.

PMID- 28446625
TI  - Use of Noncontrast Computed Tomography and Computed Tomographic Perfusion in
      Predicting Intracerebral Hemorrhage After Intravenous Alteplase Therapy.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage is a feared complication of
      intravenous alteplase therapy in patients with acute ischemic stroke. We explore
      the use of multimodal computed tomography in predicting this complication.
      METHODS: All patients were administered intravenous alteplase with/without intra
      arterial therapy. An age- and sex-matched case-control design with classic and
      conditional logistic regression techniques was chosen for analyses. Outcome was
      parenchymal hemorrhage on 24- to 48-hour imaging. Exposure variables were imaging
      (noncontrast computed tomography hypoattenuation degree, relative volume of very
      low cerebral blood volume, relative volume of cerebral blood flow <=7 mL/min.per
      100 g, relative volume of Tmax >=16 s with all volumes standardized to z axis
      coverage, mean permeability surface area product values within Tmax >=8 s volume,
      and mean permeability surface area product values within ipsilesional hemisphere)
      and clinical variables (NIHSS [National Institutes of Health Stroke Scale], onset
      to imaging time, baseline systolic blood pressure, blood glucose, serum
      creatinine, treatment type, and reperfusion status). RESULTS: One-hundred
      eighteen subjects (22 patients with parenchymal hemorrhage versus 96 without,
      median baseline NIHSS score of 15) were included in the final analysis. In
      multivariable regression, noncontrast computed tomography hypoattenuation grade
      (P<0.006) and computerized tomography perfusion white matter relative volume of
      very low cerebral blood volume (P=0.04) were the only significant variables
      associated with parenchymal hemorrhage on follow-up imaging (area under the
      curve, 0.73; 95% confidence interval, 0.63-0.83). Interrater reliability for
      noncontrast computed tomography hypoattenuation grade was moderate (kappa=0.6).
      CONCLUSIONS: Baseline hypoattenuation on noncontrast computed tomography and very
      low cerebral blood volume on computerized tomography perfusion are associated
      with development of parenchymal hemorrhage in patients with acute ischemic stroke
      receiving intravenous alteplase.

PMID- 28446627
TI  - Silicon Alleviates Nonalcoholic Steatohepatitis by Reducing Apoptosis in Aged
      Wistar Rats Fed a High-Saturated Fat, High-Cholesterol Diet.
AB  - Background: Lipoapoptosis has been identified as a key event in the progression
      of nonalcoholic fatty liver disease (NAFLD), and hence, antiapoptotic agents have
      been recommended as a possible effective treatment for nonalcoholic
      steatohepatitis (NASH). Silicon, included in meat as a functional ingredient,
      improves lipoprotein profiles and liver antioxidant defenses in aged rats fed a
      high-saturated fat, high-cholesterol diet (HSHCD). However, to our knowledge, the
      antiapoptotic effect of this potential functional meat on the liver has never
      been tested.Objective: This study was designed to evaluate the effect of silicon
      on NASH development and the potential antiapoptotic properties of silicon in aged
      rats.Methods: One-year-old male Wistar rats weighing ~500 g were fed 3
      experimental diets containing restructured pork (RP) for 8 wk: 1) a high
      saturated fat diet, as an NAFLD control, with 16.9% total fat, 0.14 g
      cholesterol/kg diet, and 46.8 mg SiO2/kg (control); 2) the HSHCD as a model of
      NASH, with 16.6% total fat, 16.3 g cholesterol/kg diet, and 46.8 mg SiO2/kg [high
      cholesterol diet (Chol-C)]; and 3) the HSHCD with silicon-supplemented RP with
      amounts of fat and cholesterol identical to those in the Chol-C diet, but with
      750 mg SiO2/kg (Chol-Si). Detailed histopathological assessments were performed,
      and the NAFLD activity score (NAS) was calculated. Liver apoptosis and damage
      markers were evaluated by Western blotting and immunohistochemical
      staining.Results: Chol-C rats had a higher mean NAS (7.4) than did control rats
      (1.9; P < 0.001). The score in Chol-Si rats (5.4) was intermediate and different
      from that in both other groups (P < 0.05). Several liver apoptosis markers
      including hepatocyte terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'
      triphosphate (dUTP) nick end labeling, cytosolic cytochrome c, apoptosis-inducing
      factor, caspases 9 and 3, and the mitochondrial Bcl-2-associated X protein (BAX)
      to-B-cell lymphoma 2 (BCL2) ratio-were 9-45% lower in Chol-Si than in Chol-C rats
      (P < 0.05) and did not differ from values in the control group.Conclusions:
      Supplemental silicon substantially affects NASH development in aged male Wistar
      rats fed an HSHCD by partially blocking apoptosis. These results suggest that
      silicon-enriched RP could be used as an effective nutritional strategy in
      preventing NASH.

PMID- 28446628
TI  - Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with
      Elevated C-Reactive Protein or alpha1-Acid Glycoprotein.
AB  - Background: Ferritin and hepcidin are markers of iron status that typically
      increase during inflammation or infection. The postpartum period is a
      physiologically unique life stage in which the relations between these proteins
      and other markers of inflammation have not been extensively studied.Objective: We
      aimed to determine whether 2 markers of inflammation [high-sensitivity C-reactive
      protein (CRP) and alpha1-acid glycoprotein (AGP)] were associated with ferritin
      or hepcidin in postpartum women in California.Methods: This is a secondary
      analysis of a randomized controlled iron-intervention trial. Plasma CRP, AGP,
      ferritin, and hepcidin were analyzed at 2 and 17 wk postpartum in 114 lactating
      women. We examined Pearson correlation coefficients between all biomarkers at
      both time points and differences in mean values of ferritin and hepcidin between
      those with and without elevated CRP and/or AGP.Results: At 2 and 17 wk
      postpartum, 58% and 26% of women had CRP >5 mg/L and 78% and 29% had AGP >1 g/L,
      respectively. Neither CRP nor AGP was significantly correlated with ferritin (r =
      0.07 and -0.06; n = 114 at 2 wk; -0.14 and -0.14; n = 95 at 17 wk) or hepcidin (r
      = 0.18 and -0.03 at 2 wk; -0.05 and -0.14 at 17 wk; P > 0.05 for all). At 2 wk,
      geometric mean plasma ferritin and hepcidin concentrations did not differ between
      women with and without elevated CRP or AGP (P > 0.5), but at 17 wk women with
      elevated CRP or AGP had lower mean (95% CI) ferritin and hepcidin than did women
      without either elevated CRP or AGP [ferritin: 30.3 ng/mL (23.4, 39.1 ng/mL)
      compared with 40.2 ng/mL (32.9, 49.2 ng/mL); P < 0.01; hepcidin: 44.3 ng/mL
      (32.3, 60.9 ng/mL) compared with 67.6 ng/mL (56.1, 81.5 ng/mL); P =
      0.02].Conclusion: Lower ferritin and hepcidin among women with elevated CRP or
      AGP at 17 wk postpartum suggests that these markers of iron status react
      differently to physiologic immune activation than to pathologic inflammatory
      states.

PMID- 28446630
TI  - Texture-Based Differences in Eating Rate Reduce the Impact of Increased Energy
      Density and Large Portions on Meal Size in Adults.
AB  - Background: Large portions and high dietary energy density promote
      overconsumption at meal times. This could be reduced by eating slowly.Objective:
      Two studies investigated whether texture-based reductions in eating rate and oral
      processing moderate consumption at breakfast in combination with variations in
      energy density and portion size.Methods: Adults attended 4 breakfast sessions (2
      * 2 repeated-measures design) to consume rice porridge, combining a 45% reduction
      in eating rate [thin porridge (140 g/min) compared with thick porridge (77
      g/min)] with a 77% increase in energy density (0.57 compared with 1.01 kcal/g) in
      study 1 [n = 61; aged 21-48 y; body mass index (BMI; in kg/m2): 16-29] and a 50%
      increase in portion size (100% compared with 150%) in study 2 (n = 53; aged 21-42
      y; BMI: 16-29). Oral processing behaviors were coded by using webcams. Porridge
      intake was measured alongside changes in rated appetite.Results: Increases in
      energy density and portion size led to increases of 80% and 13% in energy intake
      at breakfast, respectively (P < 0.001), but only portion size increased the
      weight of food consumed (13%). The thicker porridges were consumed at a slower
      rate and led to 11-13% reductions in food weight and energy intake compared with
      the thin versions (P < 0.001). Combined, the least energy was consumed when the
      thick "slow" porridge was served with a lower energy density or smaller portion
      (P < 0.05). Although intake was reduced for the thick porridges, they were
      expected to be more filling than the thin versions and experienced as equally
      satiating postconsumption.Conclusions: Adults eat in response to external
      features of the food environment. An opportunity exists to use a combination of
      energy-density dilution, smaller portions, and natural variations in food texture
      to design meals that promote reductions in energy intake while maintaining
      satiety.

PMID- 28446629
TI  - Vitamin D Receptor and Megalin Gene Polymorphisms Are Associated with
      Longitudinal Cognitive Change among African-American Urban Adults.
AB  - Background: The link between longitudinal cognitive change and polymorphisms in
      the vitamin D receptor (VDR) and MEGALIN [or LDL receptor-related protein 2
      (LRP2)] genes remains unclear, particularly among African-American (AA)
      adults.Objectives: We aimed to evaluate associations of single nucleotide
      polymorphisms (SNPs) for VDR [rs11568820 (Cdx-2:T/C), rs1544410 (BsmI:G/A),
      rs7975232 (ApaI:A/C), rs731236 (TaqI:G/A)] and LRP2 [rs3755166:G/A,rs2075252:C/T,
      rs2228171:C/T] genes with longitudinal cognitive performance change in various
      domains of cognition.Methods: Data from 1024 AA urban adult participants in the
      Healthy Aging in Neighborhoods of Diversity Across the Life Span (Baltimore,
      Maryland) with complete genetic data were used, of whom 660-797 had complete data
      on 9 cognitive test scores at baseline and/or the first follow-up examination and
      complete covariate data (~52% female; mean age: ~52 y; mean years of education:
      12.6 y). Time between examination visits 1 (2004-2009) and 2 (2009-2013) ranged
      from <1 y to ~8 y, with a mean +/- SD of 4.64 +/- 0.93 y. Latent class and
      haplotype analyses were conducted by creating gene polymorphism groups that were
      related to longitudinal annual rate of cognitive change predicted from mixed
      effects regression models.Results: Among key findings, the rs3755166:G/A MEGALIN
      SNP was associated with faster decline on the Mini-Mental State Examination
      overall (beta = -0.002, P = 0.018) and among women. VDR2 (BsmI/ApaI/TaqI: G-/A-/A
      ) SNP latent class [SNPLC; compared with VDR1 (ApaI: "AA")] was linked to faster
      decline on the Verbal Fluency Test, Categorical, in women, among whom the
      MEGALIN2 (rs2228171: "TT") SNPLC (compared with MEGALIN1:rs2228171: "CC") was
      also associated with a faster decline on the Trailmaking Test, Part B (Trails B),
      but with a slower decline on the Digit Span Backward (DS-B). Moreover, among men,
      the VDR1 SNP haplotype (SNPHAP; GCA:baT) was associated with a slower decline on
      the Trails B, whereas the MEGALIN1 SNPHAP (GCC) was associated with a faster
      decline on the DS-B, reflected as a faster decline on cognitive domain 2
      ("visual/working memory").Conclusion:VDR and MEGALIN gene variations can alter
      age-related cognitive trajectories differentially between men and women among AA
      urban adults, specifically in global mental status and domains of verbal fluency,
      visual/working memory, and executive function.

PMID- 28446631
TI  - Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect
      Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women
      of Low Vitamin B-12 Status.
AB  - Background: Low-quality dietary protein intake and vitamin B-12 deficiency could
      interact to decrease methionine transmethylation and remethylation rates during
      pregnancy and may affect epigenetic modifications of the fetal genome.Objective:
      The objective of this randomized, partially open-labeled intervention trial was
      to examine the effect of supplemental high-quality protein and vitamin B-12 on
      third-trimester methionine kinetics in pregnant Indian women with a low vitamin B
      12 status.Methods: Pregnant women with low serum vitamin B-12 concentrations
      (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received
      balanced protein-energy supplementation of 500 mL milk/d plus a 10-MUg vitamin B
      12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d)
      plus a placebo tablet (M+P group; n = 30), and the third group received a placebo
      tablet alone (P group; n = 33). Third-trimester fasting plasma amino acid
      kinetics were measured by infusing 1-13C,methyl-2H3-methionine, ring-2H5
      phenylalanine, ring-2H4-tyrosine,1-13C-glycine, and 2,3,3-2H3,15N-serine in a
      subset of participants. Placental mRNA expression of genes involved in methionine
      pathways, placental long interspersed nuclear elements 1 (LINE-1) methylation,
      and promoter methylation levels of vascular endothelial growth factor (VEGF) were
      analyzed.Results: Remethylation rates in the M+B-12, M+P, and P groups were 5.1
      +/- 1.7, 4.1 +/- 1.0, and, 5.0 +/- 1.4 MUmol ? kg-1 ? h-1, respectively (P =
      0.057), such that the percentage of transmethylation remethylated to methionine
      tended to be higher in the M+B-12 group (49.5% +/- 10.5%) than in the M+P group
      (42.3% +/- 8.4%; P = 0.053) but neither differed from the P group (44.2% +/-
      8.1%; P > 0.1). Placental mRNA expression, LINE-1, and VEGF promoter methylation
      did not differ between groups.Conclusions: Combined vitamin B-12 and balanced
      protein-energy supplementation increased the homocysteine remethylation rate in
      late pregnancy. Thus, vitamin B-12 along with balanced protein-energy
      supplementation is critical for optimal functioning of the methionine cycle in
      the third trimester of pregnancy in Indian women with low serum vitamin B-12 in
      early pregnancy. This trial was registered at clinicaltrials.gov as
      CTRI/2016/01/006578.

PMID- 28446633
TI  - Lactose Intolerance (LCT-13910C>T) Genotype Is Associated with Plasma 25
      Hydroxyvitamin D Concentrations in Caucasians: A Mendelian Randomization Study.
AB  - Background: The LCT-13910C>T gene variant is associated with lactose intolerance
      (LI) in different ethnic groups. Individuals with LI often limit or avoid dairy
      consumption, a major dietary source of vitamin D in North America, which may lead
      to inadequate vitamin D intake.Objective: The objective was to determine the
      prevalence of genotypes predictive of LI in different ethnic groups living in
      Canada and to determine whether the LCT genotype is associated with plasma
      25(OH)D concentrations.Methods: Blood samples were drawn from a total of 1495 men
      and women aged 20-29 y from the Toronto Nutrigenomics and Health Study for
      genotyping and plasma 25(OH)D analysis. Intakes of dairy were assessed by using a
      196-item food frequency questionnaire. The prevalence of LCT-13910C>T genotypes
      was compared by using chi2 analysis. Using a Mendelian randomization approach, we
      examined the association between LCT genotypes and 25(OH)D
      concentrations.Results: Approximately 32% of Caucasians, 99% of East Asians, 74%
      of South Asians, and 59% of those with other or mixed ethnicities had the CC
      genotype associated with LI. Compared with those with the TT genotype, those with
      the CC genotype had a lower mean +/- SE total dairy intake (2.15 +/- 0.09
      compared with 2.67 +/- 0.12 servings/d, P = 0.003), a lower skim-milk intake
      (0.20 +/- 0.03 compared with 0.46 +/- 0.06 servings/d, P = 0.0004), and a lower
      plasma 25(OH)D concentration (63 +/- 1.9 compared with 75.8 +/- 2.4 nmol/L, P <
      0.0001). The CT and CC genotypes were associated with a 50% and a 2-fold
      increased risk, respectively, of a suboptimal plasma 25(OH)D concentration (<75
      nmol/L).Conclusions: In Caucasians, the CC genotype that predicts LI is
      associated with a lower plasma 25(OH)D concentration, which is attributable at
      least in part to a lower intake of dairy, particularly skim milk. Increased risk
      of suboptimal concentrations of vitamin D was also observed among those with the
      CT genotype, suggesting an intermediate effect of the heterozygous genotype.

PMID- 28446634
TI  - Heartbeat: Cardiac resynchronization therapy with or without defibrillation: are
      women different?

PMID- 28446632
TI  - Dietary Methionine Restriction Regulates Liver Protein Synthesis and Gene
      Expression Independently of Eukaryotic Initiation Factor 2 Phosphorylation in
      Mice.
AB  - Background: The phosphorylation of eukaryotic initiation factor 2 (p-eIF2) during
      dietary amino acid insufficiency reduces protein synthesis and alters gene
      expression via the integrated stress response (ISR).Objective: We explored
      whether a Met-restricted (MR) diet activates the ISR to reduce body fat and
      regulate protein balance.Methods: Male and female mice aged 3-6 mo with either
      whole-body deletion of general control nonderepressible 2 (Gcn2) or liver
      specific deletion of protein kinase R-like endoplasmic reticulum kinase (Perk)
      alongside wild-type or floxed control mice were fed an obesogenic diet sufficient
      in Met (0.86%) or an MR (0.12% Met) diet for <=5 wk. Ala enrichment with
      deuterium was measured to calculate protein synthesis rates. The guanine
      nucleotide exchange factor activity of eIF2B was measured alongside p-eIF2 and
      hepatic mRNA expression levels at 2 d and 5 wk. Metabolic phenotyping was
      conducted at 4 wk, and body composition was measured throughout. Results were
      evaluated with the use of ANOVA (P < 0.05).Results: Feeding an MR diet for 2 d
      did not increase hepatic p-eIF2 or reduce eIF2B activity in wild-type or Gcn2-/-
      mice, yet many genes transcriptionally regulated by the ISR were altered in both
      strains in the same direction and amplitude. Feeding an MR diet for 5 wk
      increased p-eIF2 and reduced eIF2B activity in wild-type but not Gcn2-/- mice,
      yet ISR-regulated genes altered in both strains similarly. Furthermore, the MR
      diet reduced mixed and cytosolic but not mitochondrial protein synthesis in both
      the liver and skeletal muscle regardless of Gcn2 status. Despite the similarities
      between strains, the MR diet did not increase energy expenditure or reduce body
      fat in Gcn2-/- mice. Finally, feeding the MR diet to mice with Perk deleted in
      the liver increased hepatic p-eIF2 and altered body composition similar to floxed
      controls.Conclusions: Hepatic activation of the ISR resulting from an MR diet
      does not require p-eIF2. Gcn2 status influences body fat loss but not protein
      balance when Met is restricted.

PMID- 28446635
TI  - Pipeline to Identify Hydroxyproline-Rich Glycoproteins.
AB  - Intrinsically disordered proteins (IDPs) are functional proteins that lack a well
      defined three-dimensional structure. The study of IDPs is a rapidly growing area
      as the crucial biological functions of more of these proteins are uncovered. In
      plants, IDPs are implicated in plant stress responses, signaling, and regulatory
      processes. A superfamily of cell wall proteins, the hydroxyproline-rich
      glycoproteins (HRGPs), have characteristic features of IDPs. Their protein
      backbones are rich in the disordering amino acid proline, they contain repeated
      sequence motifs and extensive posttranslational modifications (glycosylation),
      and they have been implicated in many biological functions. HRGPs are
      evolutionarily ancient, having been isolated from the protein-rich walls of
      chlorophyte algae to the cellulose-rich walls of embryophytes. Examination of
      HRGPs in a range of plant species should provide valuable insights into how they
      have evolved. Commonly divided into the arabinogalactan proteins, extensins, and
      proline-rich proteins, in reality, a continuum of structures exists within this
      diverse and heterogenous superfamily. An inability to accurately classify HRGPs
      leads to inconsistent gene ontologies limiting the identification of HRGP classes
      in existing and emerging omics data sets. We present a novel and robust motif and
      amino acid bias (MAAB) bioinformatics pipeline to classify HRGPs into 23
      descriptive subclasses. Validation of MAAB was achieved using available genomic
      resources and then applied to the 1000 Plants transcriptome project
      (www.onekp.com) data set. Significant improvement in the detection of HRGPs using
      multiple-k-mer transcriptome assembly methodology was observed. The MAAB pipeline
      is readily adaptable and can be modified to optimize the recovery of IDPs from
      other organisms.

PMID- 28446638
TI  - Stomatal Function across Temporal and Spatial Scales: Deep-Time Trends, Land
      Atmosphere Coupling and Global Models.

PMID- 28446637
TI  - Drought-Enhanced Xylem Sap Sulfate Closes Stomata by Affecting ALMT12 and Guard
      Cell ABA Synthesis.
AB  - Water limitation of plants causes stomatal closure to prevent water loss by
      transpiration. For this purpose, progressing soil water deficit is communicated
      from roots to shoots. Abscisic acid (ABA) is the key signal in stress-induced
      stomatal closure, but ABA as an early xylem-delivered signal is still a matter of
      debate. In this study, poplar plants (Populus * canescens) were exposed to water
      stress to investigate xylem sap sulfate and ABA, stomatal conductance, and
      sulfate transporter (SULTR) expression. In addition, stomatal behavior and
      expression of ABA receptors, drought-responsive genes, transcription factors, and
      NCED3 were studied after feeding sulfate and ABA to detached poplar leaves and
      epidermal peels of Arabidopsis (Arabidopsis thaliana). The results show that
      increased xylem sap sulfate is achieved upon drought by reduced xylem unloading
      by PtaSULTR3;3a and PtaSULTR1;1, and by enhanced loading from parenchyma cells
      into the xylem via PtaALMT3b. Sulfate application caused stomatal closure in
      excised leaves and peeled epidermis. In the loss of sulfate-channel function
      mutant, Atalmt12, sulfate-triggered stomatal closure was impaired. The
      QUAC1/ALMT12 anion channel heterologous expressed in oocytes was gated open by
      extracellular sulfate. Sulfate up-regulated the expression of NCED3, a key step
      of ABA synthesis, in guard cells. In conclusion, xylem-derived sulfate seems to
      be a chemical signal of drought that induces stomatal closure via QUAC1/ALMT12
      and/or guard cell ABA synthesis.

PMID- 28446639
TI  - Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue
      versus Circulating Tumor DNA in Breast Cancer.
AB  - While identifying genomic alterations in tumor tissue is the current gold
      standard technique for molecular profiling, circulating tumor DNA (ctDNA)
      represents a noninvasive method of assessing genomic alterations using peripheral
      blood. The concordance of genomic alterations between two commercially available
      ctDNA and tissue biopsies was compared in 45 patients with breast cancer using
      paired next-generation sequencing tissue and ctDNA biopsies. Across all genes,
      concordance between the two platforms was 91.0% to 94.2%. When only considering
      genomic alterations in either assay (e.g., excluding wild type/wild type genes),
      concordance was 10.8% to 15.1% with full plus partial concordance of 13.8% to
      19.3%. Concordant mutations were associated with significantly higher variant
      allele frequency. Over half of mutations detected in either technique were not
      detected using the other biopsy technique. Including variants of unknown
      significance, the average number of alterations per patient was significantly
      higher for tissue (4.56) compared with ctDNA (2.16). When eliminating alterations
      not detectable in the ctDNA assay, mean number of alterations for tissue and
      ctDNA was similar (2.67 for tissue, 2.16 for ctDNA). Across five representative
      genes (TP53, PIK3CA, ERBB2, BRCA1, and BRCA2), sensitivity and specificity were
      35.7% and 95.0%, respectively. Concordance when genomic alterations was detected
      in either tissue or ctDNA was low with each technique detecting a significant
      amount of nonoverlapping mutations. Potential explanations for the lack of
      concordance include tumor heterogeneity, different sequencing techniques, spatial
      and temporal factors, and potential germline DNA contamination. The study
      indicates that both tissue and blood-based NGS may be necessary to describe the
      complex biology of breast cancer. Mol Cancer Ther; 16(7); 1412-20. (c)2017 AACR.

PMID- 28446636
TI  - Insights into the Evolution of Hydroxyproline-Rich Glycoproteins from 1000 Plant
      Transcriptomes.
AB  - The carbohydrate-rich cell walls of land plants and algae have been the focus of
      much interest given the value of cell wall-based products to our current and
      future economies. Hydroxyproline-rich glycoproteins (HRGPs), a major group of
      wall glycoproteins, play important roles in plant growth and development, yet
      little is known about how they have evolved in parallel with the polysaccharide
      components of walls. We investigate the origins and evolution of the HRGP
      superfamily, which is commonly divided into three major multigene families: the
      arabinogalactan proteins (AGPs), extensins (EXTs), and proline-rich proteins.
      Using motif and amino acid bias, a newly developed bioinformatics pipeline, we
      identified HRGPs in sequences from the 1000 Plants transcriptome project
      (www.onekp.com). Our analyses provide new insights into the evolution of HRGPs
      across major evolutionary milestones, including the transition to land and the
      early radiation of angiosperms. Significantly, data mining reveals the origin of
      glycosylphosphatidylinositol (GPI)-anchored AGPs in green algae and a 3- to 4
      fold increase in GPI-AGPs in liverworts and mosses. The first detection of cross
      linking (CL)-EXTs is observed in bryophytes, which suggests that CL-EXTs arose
      though the juxtaposition of preexisting SPn EXT glycomotifs with refined Y-based
      motifs. We also detected the loss of CL-EXT in a few lineages, including the
      grass family (Poaceae), that have a cell wall composition distinct from other
      monocots and eudicots. A key challenge in HRGP research is tracking individual
      HRGPs throughout evolution. Using the 1000 Plants output, we were able to find
      putative orthologs of Arabidopsis pollen-specific GPI-AGPs in basal eudicots.

PMID- 28446640
TI  - Ref-1/APE1 as a Transcriptional Regulator and Novel Therapeutic Target in
      Pediatric T-cell Leukemia.
AB  - The increasing characterization of childhood acute lymphoblastic leukemia (ALL)
      has led to the identification of multiple molecular targets but has yet to
      translate into more effective targeted therapies, particularly for high-risk,
      relapsed T-cell ALL. Searching for master regulators controlling multiple
      signaling pathways in T-ALL, we investigated the multifunctional protein redox
      factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox
      regulatory control of transcription factors important in leukemia. Leukemia
      patients' transcriptome databases showed increased expression in T-ALL of Ref-1
      and other genes of the Ref-1/SET interactome. Validation studies demonstrated
      that Ref-1 is expressed in high-risk leukemia T cells, including in patient
      biopsies. Ref-1 redox function is active in leukemia T cells, regulating the Ref
      1 target NF-kappaB, and inhibited by the redox-selective Ref-1 inhibitor E3330.
      Ref-1 expression is not regulated by Notch signaling, but is upregulated by
      glucocorticoid treatment. E3330 disrupted Ref-1 redox activity in functional
      studies and resulted in marked inhibition of leukemia cell viability, including T
      ALL lines representing different genotypes and risk groups. Potent leukemia cell
      inhibition was seen in primary cells from ALL patients, relapsed and
      glucocorticoid-resistant T-ALL cells, and cells from a murine model of Notch
      induced leukemia. Ref-1 redox inhibition triggered leukemia cell apoptosis and
      downregulation of survival genes regulated by Ref-1 targets. For the first time,
      this work identifies Ref-1 as a novel molecular effector in T-ALL and
      demonstrates that Ref-1 redox inhibition results in potent inhibition of leukemia
      T cells, including relapsed T-ALL. These data also support E3330 as a specific
      Ref-1 small-molecule inhibitor for leukemia. Mol Cancer Ther; 16(7); 1401-11.
      (c)2017 AACR.

PMID- 28446641
TI  - Risk of Pneumonitis Associated with Programmed Cell Death 1 Inhibitors in Cancer
      Patients: A Meta-analysis.
AB  - Pneumonitis, a rare but potentially life-threatening adverse event in cancer
      patients receiving programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1)
      inhibitors, has been reported in case reports, clinical trials, and retrospective
      studies. We performed a systematic review and meta-analysis to calculate the RR
      of pneumonitis associated with the use of PD-1/L1 inhibitors in randomized
      clinical trials (RCT). We searched MEDLINE, Embase, the Cochrane Central Register
      of Controlled Trials, trial registers, conference proceedings, review articles,
      and reference lists of trial publications for all relevant RCTs comparing PD-1/L1
      inhibitors to control with available data on pneumonitis. The pooled incidence,
      RR, and 95% confidence intervals (CI) were calculated using fixed effects or
      random effects model according to the heterogeneity of included trials. Twelve
      RCTs were eligible for the meta-analysis, yielding a total of 5,775 patients
      included in trials evaluating a PD-1 inhibitor; no eligible trials evaluated a PD
      L1 inhibitor. The pooled incidence of all-grade pneumonitis for patients treated
      with PD-1 inhibitors was 3.2% (95% CI, 2.3-4.5), and that of high-grade
      pneumonitis was 1.1% (95% CI, 0.7-1.7). The RR of all-grade and high-grade
      pneumonitis was 4.36 (95% CI, 2.58-7.38) and 2.86 (95% CI, 1.30-6.31),
      respectively. In a sensitivity analysis, PD-1 inhibitors were also associated
      with significantly increased risk of pneumonitis per person-month (for all grade,
      RR = 3.37; 95% CI, 1.97-5.76; for high grade, RR = 2.25; 95% CI, 1.03-4.94). PD-1
      inhibitors were associated with a significant increase of all-grade and high
      grade pneumonitis both per treatment episode and per person-month. Mol Cancer
      Ther; 16(8); 1588-95. (c)2017 AACR.

PMID- 28446643
TI  - Preventing Parkinson disease by vagotomy: Fact or fiction?

PMID- 28446642
TI  - Cotargeting mTORC and EGFR Signaling as a Therapeutic Strategy in HNSCC.
AB  - Head and neck squamous cell carcinomas (HNSCC) are frequently altered along the
      PI3K/AKT/mTORC signaling axis. Despite excellent preclinical data, the use of
      compounds targeting this pathway as monotherapy has been underwhelming in initial
      clinical trials, and identification of predictive biomarkers remains challenging.
      To investigate mTORC-specific inhibition, we tested catalytic mTORC (AZD8055) and
      PI3K/mTORC (NVP-BEZ-235) inhibitors +/- cetuximab in a panel of HNSCC cell lines
      and patient-derived xenografts (PDX). Cell lines were assayed for response to all
      agents and siRNA knockdown of targets by multiple approaches. All cell lines
      showed similar response to both drug and siRNA inhibition of both PI3K and mTORC
      pathways, with anti-EGFR combination producing modest additive effect. Five PDX
      models that presented PIK3CA mutation or intrinsic cetuximab resistance were
      treated with a combination of cetuximab and AZD8055. In vivo single-agent mTORC
      inhibition inhibited growth of one PIK3CA-mutant cancer, but had little effect on
      any PIK3CAWT or a second PIK3CA-mutant model. In all models, the combination
      therapy showed greater growth delay than monotherapy. The uniform ability of PI3K
      and mTORC inhibition to suppress the growth of HNSCC cells highlights the
      pathway's role in driving proliferation. Although single-agent therapy was
      largely ineffective in vivo, improved response of combination treatment in an
      array of PDXs suggests the potential for adding a catalytic mTORC inhibitor to
      cetuximab therapy. Overall, these results add to a growing body of evidence,
      suggesting that approaches that attempt to match biomarkers to the optimal
      therapy in HNSCC remain complex and challenging. Mol Cancer Ther; 16(7); 1257-68.
      (c)2017 AACR.

PMID- 28446645
TI  - Hypothalamus as a mediator of chronic migraine: Evidence from high-resolution
      fMRI.
AB  - OBJECTIVE: To identify pathophysiologic mechanisms of migraine chronification
      using a recently standardized protocol for high-resolution brainstem imaging of
      trigeminal nociceptive stimulation. METHODS: Eighteen episodic migraineurs (EMs),
      17 chronic migraineurs (CMs), and 19 healthy controls (HCs) underwent painful
      ammonia stimulation of the left nostril in a 3T MRI scanner. Functional images
      were acquired with a brainstem-optimized protocol for high-resolution echo-planar
      imaging. RESULTS: We detected a significantly stronger activation of the anterior
      right hypothalamus in CMs compared to HCs. To exclude the headache as a prime
      mediator of the hypothalamic activations, we compared all migraineurs with
      headaches (EMs and CMs) with all migraineurs without headaches (EMs and CMs) and
      HCs in a second analysis and found a more posterior region of the hypothalamus to
      be more activated bilaterally during headaches. CONCLUSIONS: Our data corroborate
      the fact that the hypothalamus plays a crucial role in the pathophysiology of
      migraine chronification and acute pain stage of migraineurs. While the more
      posterior part of the hypothalamus seems to be important for the acute pain
      stage, the more anterior part seems to play an important role in attack
      generation and migraine chronification.

PMID- 28446644
TI  - Body mass index and outcome after revascularization for symptomatic carotid
      artery stenosis.
AB  - OBJECTIVE: To determine whether the obesity paradox exists in patients who
      undergo carotid artery stenting (CAS) or carotid endarterectomy (CEA) for
      symptomatic carotid artery stenosis. METHODS: We combined individual patient data
      from 2 randomized trials (Endarterectomy vs Angioplasty in Patients with
      Symptomatic Severe Carotid Stenosis and Stent-Protected Angioplasty vs Carotid
      Endarterectomy) and 3 centers in a third trial (International Carotid Stenting
      Study). Baseline body mass index (BMI) was available for 1,969 patients and
      classified into 4 groups: <20, 20-<25, 25-<30, and >=30 kg/m2. Primary outcome
      was stroke or death, investigated separately for the periprocedural and
      postprocedural period (<=120 days/>120 days after randomization). This outcome
      was compared between different BMI strata in CAS and CEA patients separately, and
      in the total group. We performed intention-to-treat multivariable Cox regression
      analyses. RESULTS: Median follow-up was 2.0 years. Stroke or death occurred in
      159 patients in the periprocedural (cumulative risk 8.1%) and in 270 patients in
      the postprocedural period (rate 4.8/100 person-years). BMI did not affect
      periprocedural risk of stroke or death for patients assigned to CAS (ptrend =
      0.39) or CEA (ptrend = 0.77) or for the total group (ptrend = 0.48). Within the
      total group, patients with BMI 25-<30 had lower postprocedural risk of stroke or
      death than patients with BMI 20-<25 (BMI 25-<30 vs BMI 20-<25; hazard ratio 0.72;
      95% confidence interval 0.55-0.94). CONCLUSIONS: BMI is not associated with
      periprocedural risk of stroke or death; however, BMI 25-<30 is associated with
      lower postprocedural risk than BMI 20-<25. These observations were similar for
      CAS and CEA.

PMID- 28446646
TI  - Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM
      TD study.
AB  - OBJECTIVE: To determine the efficacy and safety of deutetrabenazine as a
      treatment for tardive dyskinesia (TD). METHODS: One hundred seventeen patients
      with moderate to severe TD received deutetrabenazine or placebo in this
      randomized, double-blind, multicenter trial. Eligibility criteria included an
      Abnormal Involuntary Movement Scale (AIMS) score of >=6 assessed by blinded
      central video rating, stable psychiatric illness, and stable psychoactive
      medication treatment. Primary endpoint was the change in AIMS score from baseline
      to week 12. Secondary endpoints included treatment success at week 12 on the
      Clinical Global Impression of Change (CGIC) and Patient Global Impression of
      Change. RESULTS: For the primary endpoint, deutetrabenazine significantly reduced
      AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard
      error] -3.0 [0.45] vs -1.6 [0.46], p = 0.019). Treatment success on CGIC (48.2%
      vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and
      placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs
      6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs
      1.7%, respectively). In addition, no worsening in parkinsonism, as measured by
      the Unified Parkinson's Disease Rating Scale motor subscale, was noted from
      baseline to week 12 in either group. CONCLUSIONS: In patients with TD,
      deutetrabenazine was well tolerated and significantly reduced abnormal movements.
      CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients
      with TD, deutetrabenazine reduces AIMS scores.

PMID- 28446647
TI  - Relationship between carotid arterial properties and cerebral white matter
      hyperintensities.
AB  - OBJECTIVE: Since arterial stiffness is a functional measure of arterial
      compliance and may be an important marker of cerebrovascular disease, we examined
      the association of carotid artery stiffness with white matter hyperintensity
      volume (WMHV) in a cross-sectional study of 1,166 stroke-free participants.
      METHODS: Carotid beta stiffness index (STIFF) was assessed by M-mode ultrasound
      of the common carotid artery and calculated as the ratio of natural log of the
      difference between systolic and diastolic blood pressure over STRAIN, a ratio of
      the difference between carotid systolic and diastolic diameter (DD) divided by
      DD. WMHV was measured by fluid-attenuated inversion recovery MRI. The
      associations of STIFF, DD, and STRAIN with WMHV were examined using linear
      regression after adjusting for sociodemographic, lifestyle, and vascular risk
      factors. RESULTS: In a fully adjusted model, larger carotid DD was significantly
      associated with greater log-WMHV (beta = 0.09, p = 0.001). STIFF and STRAIN were
      not significantly associated with WMHV. In adjusted analyses stratified by race
      ethnicity, STRAIN (beta = -1.78, p = 0.002) and DD (beta = 0.11, p = 0.001) were
      both associated with greater log-WMHV among Hispanic participants, but not among
      black or white participants. CONCLUSIONS: Large carotid artery diameters are
      associated with greater burden of white matter hyperintensity (WMH) in this
      multiethnic population. The association between increased diameters, decreased
      STRAIN, and greater WMH burden is more pronounced among Hispanics. These
      associations suggest a potential important pathophysiologic role of extracranial
      large artery remodeling in the burden of WMH.

PMID- 28446650
TI  - Asymptomatic carotid stenosis: Why a moratorium is needed on intervention outside
      clinical trials.

PMID- 28446649
TI  - Nothing like a spirited debate!

PMID- 28446648
TI  - Pregabalin use early in pregnancy and the risk of major congenital malformations.
AB  - OBJECTIVE: To assess whether first-trimester exposure to pregabalin is associated
      with an increased risk of major congenital malformations, as recently suggested
      in a pregnancy registry study. METHODS: We performed a cohort study nested in the
      US Medicaid Analytic eXtract (MAX). The study population included 1,323,432
      pregnancies resulting in a live-born infant between 2000 and 2010. We examined
      the risk of major congenital malformations among infants born to women exposed to
      pregabalin during the first trimester compared with women unexposed to
      anticonvulsants. We used propensity score fine stratification to control for >50
      potential confounders, and we estimated relative risks (RRs) and 95% confidence
      intervals (CIs) in generalized linear models. The analyses were replicated in the
      Truven Health MarketScan Commercial Database (MarketScan). Pooled estimates based
      on the adjusted RR produced in MAX, MarketScan, and the previous registry study
      were calculated. RESULTS: Of 477 infants exposed to pregabalin during the first
      trimester in MAX, 28 (5.9%) had malformations compared to 3.3% in nonexposed
      infants. The crude RR of major congenital malformations for pregabalin was 1.80
      (95% CI 1.26-2.58). After propensity score adjustment, the RR moved to 1.16 (95%
      CI 0.81-1.67). Restriction to pregabalin monotherapy and sensitivity analyses
      produced similar results. The adjusted RR for major congenital malformations for
      the 174 infants exposed in MarketScan was 1.03 (95% CI 0.56-1.90). The pooled RR
      was 1.33 (95% CI 0.83-2.15) for pregabalin any use and 1.02 (95% CI 0.69-1.51)
      for pregabalin monotherapy. CONCLUSIONS: Findings did not confirm the suggested
      teratogenic effects of pregabalin, although they cannot rule out the possibility
      of a small effect.

PMID- 28446651
TI  - How small can the epileptogenic region be? A case in point.
AB  - OBJECTIVE: To present a case that demonstrates that seizures and interictal
      disturbances can be driven by a small area of functionally abnormal cortex.
      METHODS: Two novel functional MRI network analysis methods were used to
      supplement conventional seizure and lesion localization methods: (1) regional
      homogeneity to quantify local connectivity, or synchrony, with a resolution of
      less than 1 cm3 of cortex; and (2) small-worldness to combine information about
      whole brain network segregation and integration. RESULTS: After a small
      corticectomy in the dominant supramarginal gyrus (13 * 7 * 6 mm) limited to the
      area of abnormal local connectivity, and smaller than the PET and SPECT
      abnormalities, the patient has been seizure-free for 3 years with no language
      deficit. Whole brain network characteristics normalized (small-worldness) to that
      of healthy controls. CONCLUSIONS: This case demonstrates that small areas of
      cortex may be highly epileptogenic, drive intractable epilepsy, and disrupt large
      scale networks likely to be involved in core cognitive functions.

PMID- 28446652
TI  - Asymptomatic carotid stenosis: Medicine alone or combined with carotid
      revascularization.
AB  - Two positive randomized trials established carotid endarterectomy (CEA) as a
      superior treatment to medical management alone for the treatment of asymptomatic
      carotid artery stenosis. However, advances in medical therapy have led to an
      active and spirited debate about the best treatment for asymptomatic carotid
      stenosis. The Carotid Revascularization and Medical Management for Asymptomatic
      Carotid Stenosis (CREST 2) trial aims to better define the best treatment for the
      average patient with severe asymptomatic carotid stenosis. Enrollment in the
      trial may be hampered by strong opinions on either side of the debate. It is
      important to realize that equipoise exists and that neither the old data on CEA
      nor the new data on optimal medical therapy provide a rigorous answer. The
      assumption that medical therapy has already been proven superior to
      revascularization procedures may hinder both enrollment in the trial and
      technical advancements in revascularization procedures.

PMID- 28446654
TI  - Optimal management of patients with asymptomatic carotid stenosis.

PMID- 28446653
TI  - Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study.
AB  - OBJECTIVE: To examine whether vagotomy decreases the risk of Parkinson disease
      (PD). METHODS: Using data from nationwide Swedish registers, we conducted a
      matched-cohort study of 9,430 vagotomized patients (3,445 truncal and 5,978
      selective) identified between 1970 and 2010 and 377,200 reference individuals
      from the general population individually matched to vagotomized patients by sex
      and year of birth with a 40:1 ratio. Participants were followed up from the date
      of vagotomy until PD diagnosis, death, emigration out of Sweden, or December 31,
      2010, whichever occurred first. Vagotomy and PD were identified from the Swedish
      Patient Register. We estimated hazard ratios (HRs) with 95% confidence intervals
      (CIs) using Cox models stratified by matching variables, adjusting for country of
      birth, chronic obstructive pulmonary disease, diabetes mellitus, vascular
      diseases, rheumatologic disease, osteoarthritis, and comorbidity index. RESULTS:
      A total of 4,930 cases of incident PD were identified during 7.3 million person
      years of follow-up. PD incidence (per 100,000 person-years) was 61.8 among
      vagotomized patients (80.4 for truncal and 55.1 for selective) and 67.5 among
      reference individuals. Overall, vagotomy was not associated with PD risk (HR
      0.96, 95% CI 0.78-1.17). However, there was a suggestion of lower risk among
      patients with truncal vagotomy (HR 0.78, 95% CI 0.55-1.09), which may be driven
      by truncal vagotomy at least 5 years before PD diagnosis (HR 0.59, 95% CI 0.37
      0.93). Selective vagotomy was not related to PD risk in any analyses.
      CONCLUSIONS: Although overall vagotomy was not associated the risk of PD, we
      found suggestive evidence for a potential protective effect of truncal, but not
      selective, vagotomy against PD development.

PMID- 28446655
TI  - Intensive intervention and cognitive impairment: Are lifestyle changes enough for
      a good brain?

PMID- 28446656
TI  - Effect of a long-term intensive lifestyle intervention on prevalence of cognitive
      impairment.
AB  - OBJECTIVE: To assess whether an average of 10 years of lifestyle intervention
      designed to reduce weight and increase physical activity lowers the prevalence of
      cognitive impairment among adults at increased risk due to type 2 diabetes and
      obesity or overweight. METHODS: Central adjudication of mild cognitive impairment
      and probable dementia was based on standardized cognitive test battery scores
      administered to 3,802 individuals who had been randomly assigned, with equal
      probability, to either the lifestyle intervention or the diabetes support and
      education control. When scores fell below a prespecified threshold, functional
      information was obtained through proxy interview. RESULTS: Compared with control,
      the intensive lifestyle intervention induced and maintained marked differences in
      weight loss and self-reported physical activity throughout follow-up. At an
      average (range) of 11.4 (9.5-13.5) years after enrollment, when participants'
      mean age was 69.6 (54.9-87.2) years, the prevalence of mild cognitive impairment
      and probable dementia was 6.4% and 1.8%, respectively, in the intervention group,
      compared with 6.6% and 1.8%, respectively, in the control group (p = 0.93). The
      lack of an intervention effect on the prevalence of cognitive impairment was
      consistent among individuals grouped by cardiovascular disease history, diabetes
      duration, sex, and APOE epsilon4 allele status (all p >= 0.50). However, there
      was evidence (p = 0.03) that the intervention effect ranged from benefit to harm
      across participants ordered from lowest to highest baseline BMI. CONCLUSIONS: Ten
      years of behavioral weight loss intervention did not result in an overall
      difference in the prevalence of cognitive impairment among overweight or obese
      adults with type 2 diabetes. CLINICALTRIALSGOV IDENTIFIER: NCT00017953 (Action
      for Health in Diabetes). LEVEL OF EVIDENCE: This study provides Class II evidence
      that for overweight adults with type 2 diabetes, a lifestyle intervention
      designed to reduce weight and increase physical activity does not lower the risk
      of cognitive impairment.

PMID- 28446657
TI  - Alcohol use and risk of intracerebral hemorrhage.
AB  - OBJECTIVE: To analyze the dose-risk relationship for alcohol consumption and
      intracerebral hemorrhage (ICH) in the Ethnic/Racial Variations of Intracerebral
      Hemorrhage (ERICH) study. METHODS: ERICH is a multicenter, prospective, case
      control study, designed to recruit 1,000 non-Hispanic white patients, 1,000 non
      Hispanic black patients, and 1,000 Hispanic patients with ICH. Cases were matched
      1:1 to ICH-free controls by age, sex, race/ethnicity, and geographic area.
      Comprehensive interviews included questions regarding alcohol consumption.
      Patterns of alcohol consumption were categorized as none, rare (<1 drink per
      month), moderate (>=1 drink per month and <=2 drinks per day), intermediate (>2
      drinks per day and <5 drinks per day), and heavy (>=5 drinks per day). ICH risk
      was calculated using the no-alcohol use category as the reference group. RESULTS:
      Multivariable analyses demonstrated an ordinal trend for alcohol consumption:
      rare (odds ratio [OR] 0.57, p < 0.0001), moderate (OR 0.65, p < 0.0001),
      intermediate (OR 0.82, p = 0.2666), and heavy alcohol consumption (OR 1.77, p =
      0.0003). Subgroup analyses demonstrated an association of rare and moderate
      alcohol consumption with decreased risk of both lobar and nonlobar ICH. Heavy
      alcohol consumption demonstrated a strong association with increased nonlobar ICH
      risk (OR 2.04, p = 0.0003). Heavy alcohol consumption was associated with
      significant increase in nonlobar ICH risk in black (OR 2.34, p = 0.0140) and
      Hispanic participants (OR 12.32, p < 0.0001). A similar association was not found
      in white participants. CONCLUSIONS: This study demonstrated potential protective
      effects of rare and moderate alcohol consumption on ICH risk. Heavy alcohol
      consumption was associated with increased ICH risk. Race/ethnicity was a
      significant factor in alcohol-associated ICH risk; heavy alcohol consumption in
      black and Hispanic participants poses significant nonlobar ICH risk.

PMID- 28446658
TI  - How Does Expectation Shape Object-Based Attentional Selection?

PMID- 28446660
TI  - Correction: Picciotto and Esch, "Editor Column: Progressions".

PMID- 28446659
TI  - Aducanumab Therapy Ameliorates Calcium Overload in a Mouse Model of Alzheimer's
      Disease.

PMID- 28446662
TI  - Do guidelines for treating chest disease in children use Cochrane Reviews
      effectively? A systematic review.
AB  - Cochrane Reviews summarise best evidence and should inform guidelines. We
      assessed the use of Cochrane Reviews in the UK guidelines for paediatric
      respiratory disease. We found 21 guidelines which made 1025 recommendations, of
      which 96 could be informed by a Cochrane Review. In 38/96 recommendations (40%),
      some or all of the relevant Cochrane Reviews were not cited. We linked
      recommendations to 140 Cochrane Reviews. In 37/140 (26%) cases, the guideline
      recommendation did not fully agree with the Cochrane Review. Guideline developers
      may fail to use Cochrane Reviews or may make recommendations which are not in
      line with best evidence.

PMID- 28446663
TI  - Short lung transplant donor telomere length is associated with decreased CLAD
      free survival.
AB  - Telomere length (TL) decreases with cellular ageing and biological stressors. As
      advanced donor and recipient ages are risk factors for chronic lung allograft
      dysfunction (CLAD), we hypothesised that decreased age-adjusted donor TL would
      predict earlier onset of CLAD. Shorter donor TL was associated with increased
      risk of CLAD or death (HR 1.26 per 1 kb TL decrease, 95% CI 1.03 to 1.54),
      particularly for young donors. Recipient TL was associated with cytopenias but
      not CLAD. Shorter TL was also seen in airway epithelium for subjects progressing
      to CLAD (p=0.02). Allograft TL may contribute to CLAD pathogenesis and facilitate
      risk stratification.

PMID- 28446664
TI  - Analysis of Competing HIV-1 Splice Donor Sites Uncovers a Tight Cluster of
      Splicing Regulatory Elements within Exon 2/2b.
AB  - The HIV-1 accessory protein Vif is essential for viral replication by
      counteracting the host restriction factor APOBEC3G (A3G), and balanced levels of
      both proteins are required for efficient viral replication. Noncoding exons 2/2b
      contain the Vif start codon between their alternatively used splice donors 2 and
      2b (D2 and D2b). For vif mRNA, intron 1 must be removed while intron 2 must be
      retained. Thus, splice acceptor 1 (A1) must be activated by U1 snRNP binding to
      either D2 or D2b, while splicing at D2 or D2b must be prevented. Here, we unravel
      the complex interactions between previously known and novel components of the
      splicing regulatory network regulating HIV-1 exon 2/2b inclusion in viral mRNAs.
      In particular, using RNA pulldown experiments and mass spectrometry analysis, we
      found members of the heterogeneous nuclear ribonucleoparticle (hnRNP) A/B family
      binding to a novel splicing regulatory element (SRE), the exonic splicing
      silencer ESS2b, and the splicing regulatory proteins Tra2/SRSF10 binding to the
      nearby exonic splicing enhancer ESE2b. Using a minigene reporter, we performed
      bioinformatics HEXplorer-guided mutational analysis to narrow down SRE motifs
      affecting splice site selection between D2 and D2b. Eventually, the impacts of
      these SREs on the viral splicing pattern and protein expression were exhaustively
      analyzed in viral particle production and replication experiments. Masking of
      these protein binding sites by use of locked nucleic acids (LNAs) impaired Vif
      expression and viral replication.IMPORTANCE Based on our results, we propose a
      model in which a dense network of SREs regulates vif mRNA and protein expression,
      crucial to maintain viral replication within host cells with varying A3G levels
      and at different stages of infection. This regulation is maintained by several
      serine/arginine-rich splicing factors (SRSF) and hnRNPs binding to those
      elements. Targeting this cluster of SREs with LNAs may lead to the development of
      novel effective therapeutic strategies.

PMID- 28446665
TI  - Dense Array of Spikes on HIV-1 Virion Particles.
AB  - HIV-1 is rare among viruses for having a low number of envelope glycoprotein
      (Env) spikes per virion, i.e., ~7 to 14. This exceptional feature has been
      associated with avoidance of humoral immunity, i.e., B cell activation and
      antibody neutralization. Virus-like particles (VLPs) with increased density of
      Env are being pursued for vaccine development; however, these typically require
      protein engineering that alters Env structure. Here, we used instead a strategy
      that targets the producer cell. We employed fluorescence-activated cell sorting
      (FACS) to sort for cells that are recognized by trimer cross-reactive broadly
      neutralizing antibody (bnAb) and not by nonneutralizing antibodies. Following
      multiple iterations of FACS, cells and progeny virions were shown to display
      higher levels of antigenically correct Env in a manner that correlated between
      cells and cognate virions (P = 0.027). High-Env VLPs, or hVLPs, were shown to be
      monodisperse and to display more than a 10-fold increase in spikes per particle
      by electron microscopy (average, 127 spikes; range, 90 to 214 spikes). Sequencing
      revealed a partial truncation in the C-terminal tail of Env that had emerged in
      the sort; however, iterative rounds of "cell factory" selection were required for
      the high-Env phenotype. hVLPs showed greater infectivity than standard
      pseudovirions but largely similar neutralization sensitivity. Importantly, hVLPs
      also showed superior activation of Env-specific B cells. Hence, high-Env HIV-1
      virions, obtained through selection of producer cells, represent an adaptable
      platform for vaccine design and should aid in the study of native Env.IMPORTANCE
      The paucity of spikes on HIV is a unique feature that has been associated with
      evasion of the immune system, while increasing spike density has been a goal of
      vaccine design. Increasing the density of Env by modifying it in various ways has
      met with limited success. Here, we focused instead on the producer cell. Cells
      that stably express HIV spikes were screened on the basis of high binding by
      bnAbs and low binding by nonneutralizing antibodies. Levels of spikes on cells
      correlated well with those on progeny virions. Importantly, high-Env virus-like
      particles (hVLPs) were produced with a manifest array of well-defined spikes, and
      these were shown to be superior in activating desirable B cells. Our study
      describes HIV particles that are densely coated with functional spikes, which
      should facilitate the study of HIV spikes and their development as immunogens.

PMID- 28446666
TI  - Mouse Saliva Inhibits Transit of Influenza Virus to the Lower Respiratory Tract
      by Efficiently Blocking Influenza Virus Neuraminidase Activity.
AB  - We previously identified a novel inhibitor of influenza virus in mouse saliva
      that halts the progression of susceptible viruses from the upper to the lower
      respiratory tract of mice in vivo and neutralizes viral infectivity in MDCK
      cells. Here, we investigated the viral target of the salivary inhibitor by using
      reverse genetics to create hybrid viruses with some surface proteins derived from
      an inhibitor-sensitive strain and others from an inhibitor-resistant strain.
      These viruses demonstrated that the origin of the viral neuraminidase (NA), but
      not the hemagglutinin or matrix protein, was the determinant of susceptibility to
      the inhibitor. Comparison of the NA sequences of a panel of H3N2 viruses with
      differing sensitivities to the salivary inhibitor revealed that surface residues
      368 to 370 (N2 numbering) outside the active site played a key role in
      resistance. Resistant viruses contained an EDS motif at this location, and
      mutation to either EES or KDS, found in highly susceptible strains, significantly
      increased in vitro susceptibility to the inhibitor and reduced the ability of the
      virus to progress to the lungs when the viral inoculum was initially confined to
      the upper respiratory tract. In the presence of saliva, viral strains with a
      susceptible NA could not be efficiently released from the surfaces of infected
      MDCK cells and had reduced enzymatic activity based on their ability to cleave
      substrate in vitro This work indicates that the mouse has evolved an innate
      inhibitor similar in function, though not in mechanism, to what humans have
      created synthetically as an antiviral drug for influenza virus.IMPORTANCE Despite
      widespread use of experimental pulmonary infection of the laboratory mouse to
      study influenza virus infection and pathogenesis, to our knowledge, mice do not
      naturally succumb to influenza. Here, we show that mice produce their own natural
      form of neuraminidase inhibitor in saliva that stops the virus from reaching the
      lungs, providing a possible mechanism through which the species may not
      experience severe influenza virus infection in the wild. We show that the murine
      salivary inhibitor targets the outer surface of the influenza virus
      neuraminidase, possibly occluding entry to the enzymatic site rather than binding
      within the active site like commercially available neuraminidase inhibitors. This
      knowledge sheds light on how the natural inhibitors of particular species combat
      infection.

PMID- 28446667
TI  - Disparate Contributions of Human Retrovirus Capsid Subdomains to Gag-Gag
      Oligomerization, Virus Morphology, and Particle Biogenesis.
AB  - The capsid domain (CA) of the retroviral Gag protein is a primary determinant of
      Gag oligomerization, which is a critical step for immature Gag lattice formation
      and virus particle budding. Although the human immunodeficiency virus type 1 (HIV
      1) CA carboxy-terminal domain (CTD) is essential for CA-CA interactions, the CA
      CTD has been suggested to be largely dispensable for human T-cell leukemia virus
      type 1 (HTLV-1) particle biogenesis. To more clearly define the roles of the HTLV
      1 CA amino-terminal domain (NTD) and CA CTD in particle biogenesis, we generated
      and analyzed a panel of Gag proteins with chimeric HIV-1/HTLV-1 CA domains.
      Subcellular distribution and protein expression levels indicated that Gag
      proteins with a chimeric HIV-1 CA NTD/HTLV-1 CA CTD did not result in Gag
      oligomerization regardless of the parent Gag background. Furthermore, chimeric
      Gag proteins with the HTLV-1 CA NTD produced particles phenotypically similar to
      HTLV-1 immature particles, highlighting the importance of the HTLV-1 CA NTD in
      HTLV-1 immature particle morphology. Taken together, these observations support
      the conclusion that the HTLV-1 CA NTD can functionally replace the HIV-1 CA CTD,
      but the HIV-1 CA NTD cannot replace the HTLV-1 CA CTD, indicating that the HTLV-1
      CA subdomains provide distinct contributions to Gag-Gag oligomerization, particle
      morphology, and biogenesis. Furthermore, we have shown for the first time that
      HIV-1 and HTLV-1 Gag domains outside the CA (e.g., matrix and nucleocapsid)
      impact Gag oligomerization as well as immature particle size and
      morphology.IMPORTANCE A key aspect in virus replication is virus particle
      assembly, which is a poorly understood process for most viruses. For
      retroviruses, the Gag structural protein is the primary driver of virus particle
      biogenesis, and the CA CTD is the primary determinant of Gag-Gag interactions for
      HIV-1. In this study, the HTLV-1 capsid amino-terminal domain was found to
      provide distinct contributions to Gag-Gag oligomerization, particle morphology,
      and biogenesis. This study provides information that will aid efforts for
      discovery of therapeutic targets for intervention.

PMID- 28446668
TI  - Serine 235 Is the Primary NS5A Hyperphosphorylation Site Responsible for
      Hepatitis C Virus Replication.
AB  - The nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV) is a
      phosphoprotein with two phosphorylation states: hypo- and hyperphosphorylation.
      Genetic mutation studies have demonstrated a cluster of serine residues
      responsible for NS5A hyperphosphorylation and functions in viral replication and
      assembly; however, the phosphorylation levels and potential interactions among
      the serine residues are unclear. We used three specific antibodies to measure
      NS5A phosphorylation at S222, S235, and S238 that were identified in our previous
      proteomics study. In the HCV (J6/JFH-1)-infected Huh7.5.1 cells, S222
      phosphorylation was barely detected, whereas S235 phosphorylation and S238
      phosphorylation were always detected in parallel in time and intracellular
      spaces. S235A mutation eliminated S238 phosphorylation whereas S238A mutation did
      not affect S235 phosphorylation, indicating that S235 phosphorylation occurs
      independently of S238 phosphorylation while S238 phosphorylation depends on S235
      phosphorylation. In line with this, immunoprecipitation coupled with
      immunoblotting showed that S235 phosphorylation existed alone without S238
      phosphorylation, whereas S238 phosphorylation existed only when S235 was
      phosphorylated on the same NS5A molecule. S235-phosphorylated NS5A constituted
      the primary hyperphosphorylated NS5A species. S235A mutation blunted viral
      replication, whereas S238A mutation did not affect replication. We concluded that
      S235 is the primary NS5A hyperphosphorylation site required for HCV replication.
      S238 is likely phosphorylated by casein kinase Ialpha, which requires a priming
      phosphorylation at S235.IMPORTANCE It has been known for years that the hepatitis
      C virus nonstructural protein 5A (NS5A) undergoes transition between two
      phosphorylation states: hypo- and hyperphosphorylation. It is also known that a
      cluster of serine residues is responsible for NS5A hyperphosphorylation and
      functions; however, the primary serine residue responsible for NS5A
      hyperphosphorylation is not clear. Here, we show for the first time that serine
      235-phosphorylated NS5A constitutes the primary hyperphosphorylated NS5A species
      required for viral replication. We also show that NS5A phosphorylation among the
      serine residues is interdependent and occurs in a directional manner, i.e.,
      phosphorylation at serine 235 leads to phosphorylation at serine 238. Our data
      provide the first proof-of-principle evidence that NS5A undergoes a sequential
      phosphorylation cascade.

PMID- 28446669
TI  - Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal
      Influenza Virus Infection.
AB  - It is possible to model the progression of influenza virus from the upper
      respiratory tract to the lower respiratory tract in the mouse using viral
      inoculum delivered in a restricted manner to the nose. In this model, infection
      with the A/Udorn/307/72 (Udorn) strain of virus results ultimately in high viral
      titers in both the trachea and lungs. In contrast, the A/Puerto Rico/8/34 (PR8)
      strain causes an infection that is almost entirely limited to the nasal passages.
      The factors that govern the progression of virus down the respiratory tract are
      not well understood. Here, we show that, while PR8 virus grows to high titers in
      the nose, an inhibitor present in the saliva blocks further progression of
      infection to the trachea and lungs and renders an otherwise lethal dose of virus
      completely asymptomatic. In vitro, the salivary inhibitor was capable of potent
      neutralization of PR8 virus and an additional 20 strains of type A virus and two
      type B strains that were tested. The exceptions were Udorn virus and the closely
      related H3N2 strains A/Port Chalmers/1/73 and A/Victoria/3/75. Characterization
      of the salivary inhibitor showed it to be independent of sialic acid and other
      carbohydrates for its function. This and other biochemical properties, together
      with its virus strain specificity and in vivo function, indicate that the mouse
      salivary inhibitor is a previously undescribed innate inhibitory molecule that
      may have evolved to provide pulmonary protection of the species from fatal
      influenza virus infection.IMPORTANCE Influenza A virus occasionally jumps from
      aquatic birds, its natural host, into mammals to cause outbreaks of varying
      severity, including pandemics in humans. Despite the laboratory mouse being used
      as a model to study influenza virus pathogenesis, natural outbreaks of influenza
      have not been reported in the species. Here, we shed light on one mechanism that
      might allow mice to be protected from influenza in the wild. We show that virus
      deposited in the mouse upper respiratory tract will not progress to the lower
      respiratory tract due to the presence of a potent inhibitor of the virus in
      saliva. Containing inhibitor-sensitive virus to the upper respiratory tract
      renders an otherwise lethal infection subclinical. This knowledge sheds light on
      how natural inhibitors may have evolved to improve survival in this species.

PMID- 28446670
TI  - Collateral Damage during Dengue Virus Infection: Making Sense of DNA by cGAS.
AB  - Early sensing of viral components or infection-induced tissue damage is a
      prerequisite for the successful control of pathogenic viruses by the host innate
      immune system. Recent results from our laboratory show how immune cells use the
      DNA-sensing machinery to detect intracellular damage generated early during
      infection by an RNA virus, namely, dengue virus (DENV). Conversely, we found that
      DENV can efficiently dismantle this sensing mechanism by targeting the cyclic GMP
      AMP synthase (cGAS) and the stimulator of interferon (IFN) genes (STING), two
      crucial host factors involved in DNA detection and type I IFN production. These
      findings highlight the relevance of the DNA-sensing mechanism in the detection
      and control of infections by RNA viruses. In this review, we discuss how DENV
      modulates the innate immune DNA-sensing pathway, activated in the context of
      cellular damage during infection.

PMID- 28446671
TI  - Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen:
      Replicating and Shielding Viral DNA during Viral Persistence.
AB  - Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong latency. The viral
      latency-associated nuclear antigen (LANA) promotes viral persistence by tethering
      the viral genome to cellular chromosomes and by participating in latent DNA
      replication. Recently, the structure of the LANA C-terminal DNA binding domain
      was solved and new cytoplasmic variants of LANA were discovered. We discuss how
      these findings contribute to our current view of LANA structure and assembly and
      of its role during viral persistence.

PMID- 28446672
TI  - Cellular Cholesterol Facilitates the Postentry Replication Cycle of Herpes
      Simplex Virus 1.
AB  - Cholesterol is an essential component of cell membranes and is required for
      herpes simplex virus 1 (HSV-1) entry (1-3). Treatment of HSV-1-infected Vero
      cells with methyl beta-cyclodextrin from 2 to 9 h postentry reduced plaque
      numbers. Transport of incoming viral capsids to the nuclear periphery was
      unaffected by the cholesterol reduction, suggesting that cell cholesterol is
      important for the HSV-1 replicative cycle at a stage(s) beyond entry, after the
      arrival of capsids at the nucleus. The synthesis and release of infectious HSV-1
      and cell-to-cell spread of infection were all impaired in cholesterol-reduced
      cells. Propagation of HSV-1 on DHCR24-/- fibroblasts, which lack the desmosterol
      to-cholesterol conversion enzyme, resulted in the generation of infectious
      extracellular virions (HSVdes) that lack cholesterol and likely contain
      desmosterol. The specific infectivities (PFU per viral genome) of HSVchol and
      HSVdes were similar, suggesting cholesterol and desmosterol in the HSV envelope
      support similar levels of infectivity. However, infected DHCR24-/- fibroblasts
      released ~1 log less infectious HSVdes and ~1.5 log fewer particles than release
      of cholesterol-containing particles (HSVchol) from parental fibroblasts,
      suggesting that the hydrocarbon tail of cholesterol facilitates viral synthesis.
      Together, the results suggest multiple roles for cholesterol in the HSV-1
      replicative cycle.IMPORTANCE HSV-1 infections are associated with a wide range of
      clinical manifestations that are of public health importance. Cholesterol is a
      key player in the complex interaction between viral and cellular factors that
      allows HSV-1 to enter host cells and establish infection. Previous reports have
      demonstrated a role for cellular cholesterol in the entry of HSV-1 into target
      cells. Here, we employed both chemical treatment and cells that were genetically
      defined to synthesize only desmosterol to demonstrate that cholesterol is
      important at stages following the initial entry and transport of viral capsids to
      the nucleus. Viral protein expression, encapsidation of the viral genome, and the
      release of mature virions were impacted by the reduction of cellular cholesterol.
      Cholesterol was also critical for cell-to-cell spread of infection. These
      findings provide new insights into the cholesterol dependence of HSV-1
      replication.

PMID- 28446673
TI  - Pacmanvirus, a New Giant Icosahedral Virus at the Crossroads between Asfarviridae
      and Faustoviruses.
AB  - African swine fever virus, a double-stranded DNA virus that infects pigs, is the
      only known member of the Asfarviridae family. Nevertheless, during our isolation
      and sequencing of the complete genome of faustovirus, followed by the description
      of kaumoebavirus, carried out over the past 2 years, we observed the emergence of
      previously unknown related viruses within this group of viruses. Here we describe
      the isolation of pacmanvirus, a fourth member in this group, which is capable of
      infecting Acanthamoeba castellanii Pacmanvirus A23 has a linear compact genome of
      395,405 bp, with a 33.62% G+C content. The pacmanvirus genome harbors 465 genes,
      with a high coding density. An analysis of reciprocal best hits shows that 31
      genes are conserved between African swine fever virus, pacmanvirus, faustovirus,
      and kaumoebavirus. Moreover, the major capsid protein locus of pacmanvirus
      appears to be different from those of kaumoebavirus and faustovirus. Overall,
      comparative and genomic analyses reveal the emergence of a new group or cluster
      of viruses encompassing African swine fever virus, faustovirus, pacmanvirus, and
      kaumoebavirus.IMPORTANCE Pacmanvirus is a newly discovered icosahedral double
      stranded DNA virus that was isolated from an environmental sample by amoeba
      coculture. We describe herein its structure and replicative cycle, along with
      genomic analysis and genomic comparisons with previously known viruses. This
      virus represents the third virus, after faustovirus and kaumoebavirus, that is
      most closely related to classical representatives of the Asfarviridae family.
      These results highlight the emergence of previously unknown double-stranded DNA
      viruses which delineate and extend the diversity of a group around the asfarvirus
      members.

PMID- 28446674
TI  - Broadening CD4+ and CD8+ T Cell Responses against Hepatitis C Virus by
      Vaccination with NS3 Overlapping Peptide Panels in Cross-Priming Liposomes.
AB  - Despite the introduction of effective drugs to treat patients with chronic
      hepatitis C virus (HCV) infection, a vaccine would be the only means to
      substantially reduce the worldwide disease burden. An incomplete understanding of
      how HCV interacts with its human host and evades immune surveillance has hampered
      vaccine development. It is generally accepted that in infected individuals, a
      narrow repertoire of exhausted T cells is a hallmark of persistent infection,
      whereas broad, vigorous CD4+ and CD8+ T cell responses are associated with
      control of acute hepatitis C. We employed a vaccine approach based on a mixture
      of peptides (pepmix) spanning the entire sequence of HCV nonstructural protein 3
      (NS3) in cross-priming cationic liposomes (CAF09) to facilitate a versatile
      presentation of all possible T cell epitopes, regardless of the HLA background of
      the vaccine recipient. Here, we demonstrate that vaccination of mice with NS3
      pepmix broadens the repertoire of epitope-specific T cells compared to the
      corresponding recombinant protein (rNS3). Moreover, vaccination with rNS3 induced
      only CD4+ T cells, whereas the NS3 pepmix induced a far more vigorous CD4+ T cell
      response and was as potent a CD8+ T cell inducer as an adenovirus-vectored
      vaccine expressing NS3. Importantly, the cellular responses are dominated by
      multifunctional T cells, such as gamma interferon-positive (IFN-gamma+) tumor
      necrosis factor alpha-positive (TNF-alpha+) coproducers, and displayed cytotoxic
      capacity in mice. In conclusion, we present a novel vaccine approach against HCV,
      inducing a broadened T cell response targeting both immunodominant and potential
      subdominant epitopes, which may be key elements to counter T cell exhaustion and
      prevent chronicity.IMPORTANCE With at least 700,000 annual deaths, development of
      a vaccine against hepatitis C virus (HCV) has high priority, but the tremendous
      ability of the virus to dodge the human immune system poses great challenges.
      Furthermore, many chronic infections, including HCV infection, have a remarkable
      ability to drive initially strong CD4+ and CD8+ T cell responses against dominant
      epitopes toward an exhausted, dysfunctional state. Thus, new and innovative
      vaccine approaches to control HCV should be evaluated. Here, we report on a novel
      peptide-based nanoparticle vaccine strategy (NS3 pepmix) aimed at generating T
      cell immunity against potential subdominant T cell epitopes that are not
      efficiently targeted by vaccination with full-length recombinant protein (rNS3)
      or infection with HCV. As proof of concept, we found that NS3 pepmix excels in
      broadening the repertoire of epitope-specific, multifunctional, and cytotoxic
      CD4+ and CD8+ T cells compared to vaccination with rNS3, which generated only
      CD4+ T cell responses.

PMID- 28446675
TI  - Comparative Genomics of Chrysochromulina Ericina Virus and Other Microalga
      Infecting Large DNA Viruses Highlights Their Intricate Evolutionary Relationship
      with the Established Mimiviridae Family.
AB  - Chrysochromulina ericina virus CeV-01B (CeV) was isolated from Norwegian coastal
      waters in 1998. Its icosahedral particle is 160 nm in diameter and encloses a 474
      kb double-stranded DNA (dsDNA) genome. This virus, although infecting a microalga
      (the haptophyceae Haptolina ericina, formerly Chrysochromulina ericina), is
      phylogenetically related to members of the Mimiviridae family, initially
      established with the acanthamoeba-infecting mimivirus and megavirus as
      prototypes. This family was later split into two genera (Mimivirus and
      Cafeteriavirus) following the characterization of a virus infecting the
      heterotrophic stramenopile Cafeteria roenbergensis (CroV). CeV, as well as two of
      its close relatives, which infect the unicellular photosynthetic eukaryotes
      Phaeocystis globosa (Phaeocystis globosa virus [PgV]) and Aureococcus
      anophagefferens (Aureococcus anophagefferens virus [AaV]), are currently
      unclassified by the International Committee on Viral Taxonomy (ICTV). The
      detailed comparative analysis of the CeV genome presented here confirms the
      phylogenetic affinity of this emerging group of microalga-infecting viruses with
      the Mimiviridae but argues in favor of their classification inside a distinct
      clade within the family. Although CeV, PgV, and AaV share more common features
      among them than with the larger Mimiviridae, they also exhibit a large complement
      of unique genes, attesting to their complex evolutionary history. We identified
      several gene fusion events and cases of convergent evolution involving
      independent lateral gene acquisitions. Finally, CeV possesses an unusual number
      of inteins, some of which are closely related despite being inserted in
      nonhomologous genes. This appears to contradict the paradigm of allele-specific
      inteins and suggests that the Mimiviridae are especially efficient in spreading
      inteins while enlarging their repertoire of homing genes.IMPORTANCE Although it
      infects the microalga Chrysochromulina ericina, CeV is more closely related to
      acanthamoeba-infecting viruses of the Mimiviridae family than to any member of
      the Phycodnaviridae, the ICTV-approved family historically including all alga
      infecting large dsDNA viruses. CeV, as well as its relatives that infect the
      microalgae Phaeocystic globosa (PgV) and Aureococcus anophagefferens (AaV),
      remains officially unclassified and a source of confusion in the literature. Our
      comparative analysis of the CeV genome in the context of this emerging group of
      alga-infecting viruses suggests that they belong to a distinct clade within the
      established Mimiviridae family. The presence of a large number of unique genes as
      well as specific gene fusion events, evolutionary convergences, and inteins
      integrated at unusual locations document the complex evolutionary history of the
      CeV lineage.

PMID- 28446676
TI  - Grass Carp Reovirus VP41 Targets Fish MITA To Abrogate the Interferon Response.
AB  - Although fish possess an efficient interferon (IFN) system to defend against
      aquatic virus infection, grass carp reovirus (GCRV) still causes hemorrhagic
      disease in grass carp. To date, GCRV's strategy for evading the fish IFN response
      is still unknown. Here, we report that GCRV VP41 inhibits fish IFN production by
      suppressing the phosphorylation of mediator of IFN regulatory factor 3 (IRF3)
      activation (MITA). First, the activation of the IFN promoter (IFNpro) stimulated
      by mitochondrial antiviral signaling protein (MAVS) and MITA was decreased by the
      overexpression of VP41, whereas such activation induced by TANK-binding kinase 1
      (TBK1) was not affected. Second, VP41 was colocalized in the cellular endoplasmic
      reticulum (ER) and associated with MITA. Furthermore, as a phosphorylation
      substrate of TBK1, VP41 significantly decreased the phosphorylation of MITA.
      Truncation assays indicated that the transmembrane (TM) region of VP41 was
      indispensable for the suppression of IFNpro activity. Finally, after infection
      with GCRV, VP41 blunted the transcription of host IFN and facilitated viral RNA
      synthesis. Taken together, our findings suggest that GCRV VP41 prevents the fish
      IFN response by attenuating the phosphorylation of MITA for viral
      evasion.IMPORTANCE MITA is thought to act as an adaptor protein to facilitate the
      phosphorylation of IRF3 by TBK1 upon viral infection, and it plays a critical
      role in innate antiviral responses. Here, we report that GCRV VP41 colocalizes
      with MITA at the ER and reduces MITA phosphorylation by acting as a decoy
      substrate of TBK1, thus inhibiting IFN production. These findings reveal GCRV's
      strategy for evading the host IFN response for the first time.

PMID- 28446677
TI  - Variable Inhibition of Zika Virus Replication by Different Wolbachia Strains in
      Mosquito Cell Cultures.
AB  - Mosquito-borne arboviruses are a major source of human disease. One strategy to
      reduce arbovirus disease is to reduce the mosquito's ability to transmit virus.
      Mosquito infection with the bacterial endosymbiont Wolbachia pipientis wMel is a
      novel strategy to reduce Aedes mosquito competency for flavivirus infection.
      However, experiments investigating cyclic environmental temperatures have shown a
      reduction in maternal transmission of wMel, potentially weakening the integration
      of this strain into a mosquito population relative to that of other Wolbachia
      strains. Consequently, it is important to investigate additional Wolbachia
      strains. All Zika virus (ZIKV) suppression studies are limited to the wMel
      Wolbachia strain. Here we show ZIKV inhibition by two different Wolbachia
      strains: wAlbB (isolated from Aedes albopictus mosquitoes) and wStri (isolated
      from the planthopper Laodelphax striatellus) in mosquito cells. Wolbachia strain
      wStri inhibited ZIKV most effectively. Single-cycle infection experiments showed
      that ZIKV RNA replication and nonstructural protein 5 translation were reduced
      below the limits of detection in wStri-containing cells, demonstrating early
      inhibition of virus replication. ZIKV replication was rescued when Wolbachia was
      inhibited with a bacteriostatic antibiotic. We observed a partial rescue of ZIKV
      growth when Wolbachia-infected cells were supplemented with cholesterol-lipid
      concentrate, suggesting competition for nutrients as one of the possible
      mechanisms of Wolbachia inhibition of ZIKV. Our data show that wAlbB and wStri
      infection causes inhibition of ZIKV, making them attractive candidates for
      further in vitro mechanistic and in vivo studies and future vector-centered
      approaches to limit ZIKV infection and spread.IMPORTANCE Zika virus (ZIKV) has
      swiftly spread throughout most of the Western Hemisphere. This is due in large
      part to its replication in and spread by a mosquito vector host. There is an
      urgent need for approaches that limit ZIKV replication in mosquitoes. One
      exciting approach for this is to use a bacterial endosymbiont called Wolbachia
      that can populate mosquito cells and inhibit ZIKV replication. Here we show that
      two different strains of Wolbachia, wAlbB and wStri, are effective at repressing
      ZIKV in mosquito cell lines. Repression of virus growth is through the inhibition
      of an early stage of infection and requires actively replicating Wolbachia Our
      findings further the understanding of Wolbachia viral inhibition and provide
      novel tools that can be used in an effort to limit ZIKV replication in the
      mosquito vector, thereby interrupting the transmission and spread of the virus.

PMID- 28446678
TI  - Differential Involvement during Latent Herpes Simplex Virus 1 Infection of the
      Superior and Inferior Divisions of the Vestibular Ganglia: Implications for
      Vestibular Neuritis.
AB  - Controversy still surrounds both the etiology and pathophysiology of vestibular
      neuritis (VN). Especially uncertain is why the superior vestibular nerve (SVN) is
      more frequently affected than the inferior vestibular nerve (IVN), which is
      partially or totally spared. To address this question, we developed an improved
      method for preparing human vestibular ganglia (VG) and nerve. Subsequently, macro
      and microanatomical as well as PCR studies were performed on 38 human ganglia
      from 38 individuals. The SVN was 2.4 mm longer than the IVN, and in 65% of the
      cases, the IVN ran in two separate bony canals, which was not the case for the
      SVN. Anastomoses between the facial and cochlear nerves were more common for the
      SVN (14/38 and 9/38, respectively) than for the IVN (7/38 and 2/38,
      respectively). Using reverse transcription-quantitative PCR (RT-qPCR), we found
      only a few latently herpes simplex virus 1 (HSV-1)-infected VG (18.4%). In cases
      of two separate neuronal fields, infected neurons were located in the superior
      part only. In summary, these PCR and micro- and macroanatomical studies provide
      possible explanations for the high frequency of SVN infection in vestibular
      neuritis.IMPORTANCE Vestibular neuritis is known to affect the superior part of
      the vestibular nerve more frequently than the inferior part. The reason for this
      clinical phenomenon remains unclear. Anatomical differences may play a role, or
      if latent HSV-1 infection is assumed, the etiology may be due to the different
      distribution of the infection. To shed further light on this subject, we
      conducted different macro- and microanatomical studies. We also assessed the
      presence of HSV-1 in VG and in different sections of the VG. Our findings add new
      information on the macro- and microanatomy of the VG as well as the
      pathophysiology of vestibular neuritis. We also show that latent HSV-1 infection
      of VG neurons is less frequent than previously reported.

PMID- 28446680
TI  - Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk
      Human Encephalitis Virus.
AB  - Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's
      murine encephalomyelitis virus (TMEV). VHEV was isolated from human material
      passaged in mice. Whether this VHEV is of human or mouse origin is therefore
      unclear. We took advantage of the species-specific activity of the nonstructural
      L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L*
      inhibits RNase L, the effector enzyme of the interferon pathway. By using
      coimmunoprecipitation and functional RNase L assays, the species specificity of
      RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains
      as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed
      the species specificity of L* activity and showed that L* from rat strain RTV-1
      inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L*
      protein was phylogenetically related to L* of mouse viruses and that it failed to
      inhibit human RNase L but readily antagonized mouse RNase L, unambiguously
      showing the mouse origin of VHEV.IMPORTANCE Defining the natural host of a virus
      can be a thorny issue, especially when the virus was isolated only once or when
      the isolation story is complex. The species Theilovirus includes Theiler's murine
      encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus
      (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus
      (VHEV), however, was isolated from mice that were inoculated with cerebrospinal
      fluid of a patient presenting with chronic encephalitis. It is therefore unclear
      whether VHEV was derived from the human sample or from the inoculated mouse. The
      L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate
      immunity, in a species-specific manner. Using binding and functional assays, we
      show that this species specificity even allows discrimination between TMEV
      strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse
      but not human RNase L, indicating that this virus originates from mice.

PMID- 28446679
TI  - Central Nervous System Infection with Borna Disease Virus Causes Kynurenine
      Pathway Dysregulation and Neurotoxic Quinolinic Acid Production.
AB  - Central nervous system infection of neonatal and adult rats with Borna disease
      virus (BDV) results in neuronal destruction and behavioral abnormalities with
      differential immune-mediated involvement. Neuroactive metabolites generated from
      the kynurenine pathway of tryptophan degradation have been implicated in several
      human neurodegenerative disorders. Here, we report that brain expression of key
      enzymes in the kynurenine pathway are significantly, but differentially, altered
      in neonatal and adult rats with BDV infection. Gene expression analysis of rat
      brains following neonatal infection showed increased expression of kynurenine
      amino transferase II (KATII) and kynurenine-3-monooxygenase (KMO) enzymes.
      Additionally, indoleamine 2,3-dioxygenase (IDO) expression was only modestly
      increased in a brain region- and time-dependent manner in neonatally infected
      rats; however, its expression was highly increased in adult infected rats. The
      most dramatic impact on gene expression was seen for KMO, whose activity promotes
      the production of neurotoxic quinolinic acid. KMO expression was persistently
      elevated in brain regions of both newborn and adult BDV-infected rats, with
      increases reaching up to 86-fold. KMO protein levels were increased in neonatally
      infected rats and colocalized with neurons, the primary target cells of BDV
      infection. Furthermore, quinolinic acid was elevated in neonatally infected rat
      brains. We further demonstrate increased expression of KATII and KMO, but not
      IDO, in vitro in BDV-infected C6 astroglioma cells. Our results suggest that BDV
      directly impacts the kynurenine pathway, an effect that may be exacerbated by
      inflammatory responses in immunocompetent hosts. Thus, experimental models of BDV
      infection may provide new tools for discriminating virus-mediated from immune
      mediated impacts on the kynurenine pathway and their relative contribution to
      neurodegeneration.IMPORTANCE BDV causes persistent, noncytopathic infection in
      vitro yet still elicits widespread neurodegeneration of infected neurons in both
      immunoincompetent and immunocompetent hosts. Here, we show that BDV infection
      induces expression of key enzymes of the kynurenine pathway in brains of newborn
      and adult infected rats and cultured astroglioma cells, shunting tryptophan
      degradation toward the production of neurotoxic quinolinic acid. Thus, our
      findings newly implicate this metabolic pathway in BDV-induced neurodegeneration.
      Given the importance of the kynurenine pathway in a wide range of human
      infections and neurodegenerative and neuropsychiatric disorders, animal models of
      BDV infection may serve as important tools for contrasting direct viral and
      indirect antiviral immune-mediated impacts on kynurenine pathway dysregulation
      and the ensuing neurodevelopmental and neuropathological consequences.

PMID- 28446681
TI  - Minute Virus of Mice Inhibits Transcription of the Cyclin B1 Gene during
      Infection.
AB  - Replication of minute virus of mice (MVM) induces a sustained cellular DNA damage
      response (DDR) which the virus then exploits to prepare the nuclear environment
      for effective parvovirus takeover. An essential aspect of the MVM-induced DDR is
      the establishment of a potent premitotic block, which we previously found to be
      independent of activated p21 and ATR/Chk1 signaling. This arrest, unlike others
      reported previously, depends upon a significant, specific depletion of cyclin B1
      and its encoding RNA, which precludes cyclin B1/CDK1 complex function, thus
      preventing mitotic entry. We show here that while the stability of cyclin B1 RNA
      was not affected by MVM infection, the production of nascent cyclin B1 RNA was
      substantially diminished at late times postinfection. Ectopic expression of NS1
      alone did not reduce cyclin B1 expression. MVM infection also reduced the levels
      of cyclin B1 protein, and RNA levels normally increased in response to DNA
      damaging reagents. We demonstrated that at times of reduced cyclin B1 expression
      during infection, there was a significantly reduced occupancy of RNA polymerase
      II and the essential mitotic transcription factor FoxM1 on the cyclin B1 gene
      promoter. Additionally, while total FoxM1 levels remained constant, there was a
      significant decrease of the phosphorylated, likely active, forms of FoxM1.
      Targeting of a constitutively active FoxM1 construct or the activation domain of
      FoxM1 to the cyclin B1 gene promoter via clustered regularly interspaced short
      palindromic repeats (CRISPR)-enzymatically inactive Cas9 in MVM-infected cells
      increased both cyclin B1 protein and RNA levels, implicating FoxM1 as a critical
      target for cyclin B1 inhibition during MVM infection.IMPORTANCE Replication of
      the parvovirus minute virus of mice (MVM) induces a sustained cellular DNA damage
      response (DDR) which the virus exploits to prepare the nuclear environment for
      effective takeover. An essential aspect of the MVM-induced DDR is establishment
      of a potent premitotic block. This block depends upon a significant, specific
      depletion of cyclin B1 and its encoding RNA that precludes cyclin B1/CDK1 complex
      functions necessary for mitotic entry. We show that reduced cyclin B1 expression
      is controlled primarily at the level of transcription initiation. Additionally,
      the essential mitotic transcription factor FoxM1 and RNA polymerase II were found
      to occupy the cyclin B1 gene promoter at reduced levels during infection.
      Recruiting a constitutively active FoxM1 construct or the activation domain of
      FoxM1 to the cyclin B1 gene promoter via CRISPR-catalytically inactive Cas9
      (dCas9) in MVM-infected cells increased expression of both cyclin B1 protein and
      RNA, implicating FoxM1 as a critical target mediating MVM-induced cyclin B1
      inhibition.

PMID- 28446682
TI  - Smartphone-controlled optogenetically engineered cells enable semiautomatic
      glucose homeostasis in diabetic mice.
AB  - With the increasingly dominant role of smartphones in our lives, mobile health
      care systems integrating advanced point-of-care technologies to manage chronic
      diseases are gaining attention. Using a multidisciplinary design principle
      coupling electrical engineering, software development, and synthetic biology, we
      have engineered a technological infrastructure enabling the smartphone-assisted
      semiautomatic treatment of diabetes in mice. A custom-designed home server
      SmartController was programmed to process wireless signals, enabling a smartphone
      to regulate hormone production by optically engineered cells implanted in
      diabetic mice via a far-red light (FRL)-responsive optogenetic interface. To
      develop this wireless controller network, we designed and implanted hydrogel
      capsules carrying both engineered cells and wirelessly powered FRL LEDs (light
      emitting diodes). In vivo production of a short variant of human glucagon-like
      peptide 1 (shGLP-1) or mouse insulin by the engineered cells in the hydrogel
      could be remotely controlled by smartphone programs or a custom-engineered
      Bluetooth-active glucometer in a semiautomatic, glucose-dependent manner. By
      combining electronic device-generated digital signals with optogenetically
      engineered cells, this study provides a step toward translating cell-based
      therapies into the clinic.

PMID- 28446683
TI  - What's old is new again: Autologous stem cell transplant for AMD.
AB  - Transplanted RPE cells derived from induced pluripotent stem cells maintained
      vision and were well tolerated in a patient with age-related macular
      degeneration.

PMID- 28446684
TI  - Nanoparticles improve economic mileage for CARs.
AB  - Targeted nanoparticles deliver chimeric antigen receptor genes to T cells in
      situ.

PMID- 28446685
TI  - Defeating Zika.
AB  - A live attenuated Zika virus vaccine produces sterilizing immunity in mice.

PMID- 28446686
TI  - The antisocial side of antibiotics.
AB  - Perinatal exposure to penicillin may result in long-lasting gut and behavioral
      changes.

PMID- 28446687
TI  - Photoactivated cells link diagnosis and therapy.
AB  - A semiautonomous system enables implanted photoactivated cells to produce glucose
      lowering hormones and maintain glucose homeostasis in diabetic mice (Shao et al,
      this issue).

PMID- 28446689
TI  - Bone CLARITY: Clearing, imaging, and computational analysis of osteoprogenitors
      within intact bone marrow.
AB  - Bone tissue harbors unique and essential physiological processes, such as
      hematopoiesis, bone growth, and bone remodeling. To enable visualization of these
      processes at the cellular level in an intact environment, we developed "Bone
      CLARITY," a bone tissue clearing method. We used Bone CLARITY and a custom-built
      light-sheet fluorescence microscope to detect the endogenous fluorescence of Sox9
      tdTomato+ osteoprogenitor cells in the tibia, femur, and vertebral column of
      adult transgenic mice. To obtain a complete distribution map of these
      osteoprogenitor cells, we developed a computational pipeline that
      semiautomatically detects individual Sox9-tdTomato+ cells in their native three
      dimensional environment. Our computational method counted all labeled
      osteoprogenitor cells without relying on sampling techniques and displayed
      increased precision when compared with traditional stereology techniques for
      estimating the total number of these rare cells. We demonstrate the value of the
      clearing-imaging pipeline by quantifying changes in the population of Sox9
      tdTomato-labeled osteoprogenitor cells after sclerostin antibody treatment. Bone
      tissue clearing is able to provide fast and comprehensive visualization of
      biological processes in intact bone tissue.

PMID- 28446688
TI  - Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy
      induced exhaustion.
AB  - Conventional cytotoxic chemotherapy is highly effective in certain cancers but
      causes dose-limiting damage to normal proliferating cells, especially
      hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics
      causes a long-term hematopoietic compromise ("exhaustion"), which limits the use
      of chemotherapy and success of cancer therapy. We show that the coadministration
      of G1T28 (trilaciclib), which is a small-molecule inhibitor of cyclin-dependent
      kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects
      murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a
      serial 5-fluorouracil treatment model. Consistent with a cell-intrinsic effect,
      we show directly preserved HSC function resulting in a more rapid recovery of
      peripheral blood counts, enhanced serial transplantation capacity, and reduced
      myeloid skewing. When administered to healthy human volunteers, G1T28
      demonstrated excellent in vivo pharmacology and transiently inhibited bone marrow
      (BM) HSPC proliferation. These findings suggest that the combination of CDK4/6
      inhibitors with cytotoxic chemotherapy should provide a means to attenuate
      therapy-induced BM exhaustion in patients with cancer.

PMID- 28446691
TI  - Key functional role of the optical properties of coral skeletons in coral ecology
      and evolution.
AB  - Multiple scattering of light on coral skeleton enhances light absorption
      efficiency of coral symbionts and plays a key role in the regulation of their
      internal diffuse light field. To understand the dependence of this enhancement on
      skeleton meso- and macrostructure, we analysed the scattering abilities of naked
      coral skeletons for 74 Indo-Pacific species. Sensitive morphotypes to thermal and
      light stress, flat-extraplanate and branching corals, showed the most efficient
      structures, while massive-robust species were less efficient. The lowest light
      enhancing scattering abilities were found for the most primitive colonial growth
      form: phaceloid. Accordingly, the development of highly efficient light
      collecting structures versus the selection of less efficient but more robust
      holobionts to cope with light stress may constitute a trade-off in the evolution
      of modern symbiotic scleractinian corals, characterizing two successful adaptive
      solutions. The coincidence of the most important structural modifications with
      epitheca decline supports the importance of the enhancement of light transmission
      across coral skeleton in modern scleractinian diversification, and the central
      role of these symbioses in the design and optimization of coral skeleton.
      Furthermore, the same ability that lies at the heart of the success of symbiotic
      corals as coral-reef-builders can also explain the 'Achilles's heel' of these
      symbioses in a warming ocean.

PMID- 28446692
TI  - Linking species habitat and past palaeoclimatic events to evolution of the
      teleost innate immune system.
AB  - Host-intrinsic factors as well as environmental changes are known to be strong
      evolutionary drivers defining the genetic foundation of immunity. Using a novel
      set of teleost genomes and a time-calibrated phylogeny, we here investigate the
      family of Toll-like receptor (TLR) genes and address the underlying evolutionary
      processes shaping the diversity of the first-line defence. Our findings reveal
      remarkable flexibility within the evolutionary design of teleost innate immunity
      characterized by prominent TLR gene losses and expansions. In the order of
      Gadiformes, expansions correlate with the loss of major histocompatibility
      complex class II (MHCII) and diversifying selection analyses support that this
      has fostered new immunological innovations in TLRs within this lineage. In
      teleosts overall, TLRs expansions correlate with species latitudinal
      distributions and maximum depth. By contrast, lineage-specific gene losses
      overlap with well-described changes in palaeoclimate (global ocean anoxia) and
      past Atlantic Ocean geography. In conclusion, we suggest that the evolvability of
      the teleost immune system has most likely played a prominent role in the survival
      and successful radiation of this lineage.

PMID- 28446690
TI  - Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium
      phosphatidylinositol 4-kinase.
AB  - As part of the global effort toward malaria eradication, phenotypic whole-cell
      screening revealed the 2-aminopyridine class of small molecules as a good
      starting point to develop new antimalarial drugs. Stemming from this series, we
      found that the derivative, MMV390048, lacked cross-resistance with current drugs
      used to treat malaria. This compound was efficacious against all Plasmodium life
      cycle stages, apart from late hypnozoites in the liver. Efficacy was shown in the
      humanized Plasmodium falciparum mouse model, and modest reductions in mouse-to
      mouse transmission were achieved in the Plasmodium berghei mouse model.
      Experiments in monkeys revealed the ability of MMV390048 to be used for full
      chemoprotection. Although MMV390048 was not able to eliminate liver hypnozoites,
      it delayed relapse in a Plasmodium cynomolgi monkey model. Both genomic and
      chemoproteomic studies identified a kinase of the Plasmodium parasite,
      phosphatidylinositol 4-kinase, as the molecular target of MMV390048. The ability
      of MMV390048 to block all life cycle stages of the malaria parasite suggests that
      this compound should be further developed and may contribute to malaria control
      and eradication as part of a single-dose combination treatment.

PMID- 28446694
TI  - Social learning and the demise of costly cooperation in humans.
AB  - Humans have a sophisticated ability to learn from others, termed social learning,
      which has allowed us to spread over the planet, construct complex societies, and
      travel to the moon. It has been hypothesized that social learning has played a
      pivotal role in making human societies cooperative, by favouring cooperation even
      when it is not favoured by genetical selection. However, this hypothesis lacks
      direct experimental testing, and the opposite prediction has also been made, that
      social learning disfavours cooperation. We experimentally tested how different
      aspects of social learning affect the level of cooperation in public-goods games.
      We found that: (i) social information never increased cooperation and usually led
      to decreased cooperation; (ii) cooperation was lowest when individuals could
      observe how successful individuals behaved; and (iii) cooperation declined
      because individuals preferred to copy successful individuals, who cooperated
      less, rather than copy common behaviours. Overall, these results suggest that
      individuals use social information to try and improve their own success, and that
      this can lead to lower levels of cooperation.

PMID- 28446693
TI  - Lipid consumption in coral larvae differs among sites: a consideration of
      environmental history in a global ocean change scenario.
AB  - The success of early life-history stages is an environmentally sensitive
      bottleneck for many marine invertebrates. Responses of larvae to environmental
      stress may vary due to differences in maternal investment of energy stores and
      acclimatization/adaptation of a population to local environmental conditions. In
      this study, we compared two populations from sites with different environmental
      regimes (Moorea and Taiwan). We assessed the responses of Pocillopora damicornis
      larvae to two future co-occurring environmental stressors: elevated temperature
      and ocean acidification. Larvae from Taiwan were more sensitive to temperature,
      producing fewer energy-storage lipids under high temperature. In general,
      planulae in Moorea and Taiwan responded similarly to pCO2 Additionally, corals in
      the study sites with different environments produced larvae with different
      initial traits, which may have shaped the different physiological responses
      observed. Notably, under ambient conditions, planulae in Taiwan increased their
      stores of wax ester and triacylglycerol in general over the first 24 h of their
      dispersal, whereas planulae from Moorea consumed energy-storage lipids in all
      cases. Comparisons of physiological responses of P. damicornis larvae to
      conditions of ocean acidification and warming between sites across the species'
      biogeographic range illuminates the variety of physiological responses maintained
      within P. damicornis, which may enhance the overall persistence of this species
      in the light of global climate change.

PMID- 28446695
TI  - Breaking the cipher: ant eavesdropping on the variational trail pheromone of its
      termite prey.
AB  - Predators may eavesdrop on their prey using innate signals of varying nature. In
      regards to social prey, most of the prey signals are derived from social
      communication and may therefore be highly complex. The most efficient predators
      select signals that provide the highest benefits. Here, we showed the use of
      eusocial prey signals by the termite-raiding ant Odontoponera transversaO.
      transversa selected the trail pheromone of termites as kairomone in several
      species of fungus-growing termites (Termitidae: Macrotermitinae: Odontotermes
      yunnanensis, Macrotermes yunnanensis, Ancistrotermes dimorphus). The most
      commonly predated termite, O. yunnanensis, was able to regulate the trail
      pheromone component ratios during its foraging activity. The ratio of the two
      trail pheromone compounds was correlated with the number of termites in the
      foraging party. (3Z)-Dodec-3-en-1-ol (DOE) was the dominant trail pheromone
      component in the initial foraging stages when fewer termites were present. Once a
      trail was established, (3Z,6Z)-dodeca-3,6-dien-1-ol (DDE) became the major
      recruitment component in the trail pheromone and enabled mass recruitment of nest
      mates to the food source. Although the ants could perceive both components, they
      revealed stronger behavioural responses to the recruitment component, DDE, than
      to the common major component, DOE. In other words, the ants use the trail
      pheromone information as an indication of suitable prey abundance, and regulate
      their behavioural responses based on the changing trail pheromone component. The
      eavesdropping behaviour in ants therefore leads to an arms race between predator
      and prey where the species specific production of trail pheromones in termites is
      targeted by predatory ant species.

PMID- 28446696
TI  - Spiders in caves.
AB  - World experts of different disciplines, from molecular biology to macro-ecology,
      recognize the value of cave ecosystems as ideal ecological and evolutionary
      laboratories. Among other subterranean taxa, spiders stand out as intriguing
      model organisms for their ecological role of top predators, their unique
      adaptations to the hypogean medium and their sensitivity to anthropogenic
      disturbance. As the description of the first eyeless spider (Stalita taenaria),
      an array of papers on subterranean spider biology, ecology and evolution has been
      published, but a comprehensive review on these topics is still lacking. We
      provide a general overview of the spider families recorded in hypogean habitats
      worldwide, we review the different adaptations of hypogean spiders to
      subterranean life, and we summarize the information gathered so far about their
      origin, population structure, ecology and conservation status. Finally, we point
      out the limits of the knowledge we currently have regarding hypogean spiders,
      aiming to stimulate future research.

PMID- 28446697
TI  - Hydrodynamic regime determines the feeding success of larval fish through the
      modulation of strike kinematics.
AB  - Larval fishes experience extreme mortality rates, with 99% of a cohort perishing
      within days after starting to actively feed. While recent evidence suggests that
      hydrodynamic factors contribute to constraining larval feeding during early
      ontogeny, feeding is a complex process that involves numerous interacting
      behavioural and biomechanical components. How these components change throughout
      ontogeny and how they contribute to feeding remain unclear. Using 339
      observations of larval feeding attempts, we quantified the effects of
      morphological and behavioural traits on feeding success of Sparus aurata larvae
      during early ontogeny. Feeding success was determined using high-speed
      videography, under both natural and increased water viscosity treatments.
      Successful strikes were characterized by Reynolds numbers that were an order of
      magnitude higher than those of failed strikes. The pattern of increasing strike
      success with increasing age was driven by the ontogeny of traits that facilitate
      the transition to higher Reynolds numbers. Hence, the physical growth of a larva
      plays an important role in its transition to a hydrodynamic regime of higher
      Reynolds numbers, in which suction feeding is more effective.

PMID- 28446698
TI  - Adaptation to a latitudinal thermal gradient within a widespread copepod species:
      the contributions of genetic divergence and phenotypic plasticity.
AB  - Understanding how populations adapt to heterogeneous thermal regimes is essential
      for comprehending how latitudinal gradients in species diversification are
      formed, and how taxa will respond to ongoing climate change. Adaptation can occur
      by innate genetic factors, by phenotypic plasticity, or by a combination of both
      mechanisms. Yet, the relative contribution of such mechanisms to large-scale
      latitudinal gradients of thermal tolerance across conspecific populations remains
      unclear. We examine thermal performance in 11 populations of the intertidal
      copepod Tigriopus californicus, ranging from Baja California Sur (Mexico) to
      British Columbia (Canada). Common garden experiments show that survivorship to
      acute heat-stress differs between populations (by up to 3.8 degrees C in LD50
      values), reflecting a strong genetic thermal adaptation. Using a split-brood
      experiment with two rearing temperatures, we also show that developmental
      phenotypic plasticity is beneficial to thermal tolerance (by up to 1.3 degrees
      C), and that this effect differs across populations. Although genetic divergence
      in heat tolerance strongly correlates with latitude and temperature, differences
      in the plastic response do not. In the context of climate warming, our results
      confirm the general prediction that low-latitude populations are most susceptible
      to local extinction because genetic adaptation has placed physiological limits
      closer to current environmental maxima, but our results also contradict the
      prediction that phenotypic plasticity is constrained at lower latitudes.

PMID- 28446699
TI  - Polydomy enhances foraging performance in ant colonies.
AB  - Collective foraging confers benefits in terms of reduced predation risk and
      access to social information, but it heightens local competition when resources
      are limited. In social insects, resource limitation has been suggested as a
      possible cause for the typical decrease in per capita productivity observed with
      increasing colony size, a phenomenon known as Michener's paradox. Polydomy
      (distribution of a colony's brood and workers across multiple nests) is believed
      to help circumvent this paradox through its positive effect on foraging
      efficiency, but there is still little supporting evidence for this hypothesis.
      Here, we show experimentally that polydomy enhances the foraging performance of
      food-deprived Temnothorax nylanderi ant colonies via several mechanisms. First,
      polydomy influences task allocation within colonies, resulting in faster
      retrieval of protein resources. Second, communication between sister nests
      reduces search times for far away resources. Third, colonies move queens, brood
      and workers across available nest sites in response to spatial heterogeneities in
      protein and carbohydrate resources. This suggests that polydomy represents a
      flexible mechanism for space occupancy, helping ant colonies adjust to the
      environment.

PMID- 28446700
TI  - Rapid polygenic response to secondary contact in a hybrid species.
AB  - Secondary contact between closely related species can have genetic consequences.
      Competition for essential resources may lead to divergence in heritable traits
      that reduces interspecific competition leading to increased rate of genetic
      divergence. Conversely, hybridization and backcrossing can lead to genetic
      convergence. Here, we study a population of a hybrid species, the Italian sparrow
      (Passer italiae), before and after it came into secondary contact with one of its
      parent species, the Spanish sparrow (P. hispaniolensis), in 2013. We demonstrate
      strong consequences of interspecific competition: Italian sparrows were kept away
      from a popular feeding site by its parent species, resulting in poorer body
      condition and a significant drop in population size. Although no significant
      morphological change could be detected, after only 3 years of sympatry, the
      Italian sparrows had diverged significantly from the Spanish sparrows across a
      set of 81 protein-coding genes. These temporal genetic changes are mirrored by
      genetic divergence observed in older sympatric Italian sparrow populations within
      the same area of contact. Compared with microallopatric birds, sympatric ones are
      genetically more diverged from Spanish sparrows. Six significant outlier genes in
      the temporal and spatial comparison (i.e. showing the greatest displacement) have
      all been found to be associated with learning and neural development in other
      bird species.

PMID- 28446701
TI  - Wind and rain are the primary climate factors driving changing phenology of an
      aerial insectivore.
AB  - While the ecological effects of climate change have been widely observed, most
      efforts to document these impacts in terrestrial systems have concentrated on the
      impacts of temperature. We used tree swallow (Tachycineta bicolor) nest
      observations from two widely separated sites in central Alaska to examine the
      aspects of climate affecting breeding phenology at the northern extent of this
      species' range. We found that two measures of breeding phenology, annual lay and
      hatch dates, are more strongly predicted by windiness and precipitation than by
      temperature. At our longest-monitored site, breeding phenology has advanced at
      nearly twice the rate seen in more southern populations, and these changes
      correspond to long-term declines in windiness. Overall, adverse spring climate
      conditions known to negatively impact foraging success of swallows (wet, windy
      weather) appear to influence breeding phenology more than variation in
      temperature. Separate analyses show that short windy periods significantly delay
      initiation of individual clutches within years. While past reviews have
      emphasized that increasing variability in climate conditions may create
      physiological and ecological challenges for natural populations, we find that
      long-term reductions in inclement weather corresponded to earlier reproduction in
      one of our study populations. To better predict climate change impacts,
      ecologists need to more carefully test effects of multiple climate variables,
      including some, like windiness, that may be of paramount importance to some
      species, but have rarely been considered as strong drivers of ecological
      responses to climate alteration.

PMID- 28446702
TI  - Alteration of cerebrovascular haemodynamic patterns due to atrial fibrillation:
      an in silico investigation.
AB  - There has recently been growing evidence that atrial fibrillation (AF), the most
      common cardiac arrhythmia, is independently associated with the risk of dementia.
      This represents a very recent frontier with high social impact for the number of
      individuals involved and for the expected increase in AF incidence in the next 40
      years. Although a number of potential haemodynamic processes, such as
      microembolisms, altered cerebral blood flow, hypoperfusion and microbleeds, arise
      as connecting links between the two pathologies, the causal mechanisms are far
      from clear. An in silico approach is proposed that combines in sequence two
      lumped-parameter schemes, for the cardiovascular system and the cerebral
      circulation. The systemic arterial pressure is obtained from the cardiovascular
      system and used as the input for the cerebral circulation, with the aim of
      studying the role of AF on the cerebral haemodynamics with respect to normal
      sinus rhythm (NSR), over a 5000 beat recording. In particular, the alteration of
      the haemodynamic (pressure and flow rate) patterns in the microcirculation during
      AF is analysed by means of different statistical tools, from correlation
      coefficients to autocorrelation functions, crossing times, extreme values
      analysis and multivariate linear regression models. A remarkable signal
      alteration, such as a reduction in signal correlation (NSR, about 3 s; AF, less
      than 1 s) and increased probability (up to three to four times higher in AF than
      in NSR) of extreme value events, emerges for the peripheral brain circulation.
      The described scenario offers a number of plausible cause-effect mechanisms that
      might explain the occurrence of critical events and the haemodynamic links
      relating to AF and dementia.

PMID- 28446703
TI  - Efficient use of sentinel sites: detection of invasive honeybee pests and
      diseases in the UK.
AB  - Sentinel sites, where problems can be identified early or investigated in detail,
      form an important part of planning for exotic disease outbreaks in humans,
      livestock and plants. Key questions are: how many sentinels are required, where
      should they be positioned and how effective are they at rapidly identifying new
      invasions? The sentinel apiary system for invasive honeybee pests and diseases
      illustrates the costs and benefits of such approaches. Here, we address these
      issues with two mathematical modelling approaches. The first approach is generic
      and uses probabilistic arguments to calculate the average number of affected
      sites when an outbreak is first detected, providing rapid and general insights
      that we have applied to a range of infectious diseases. The second approach uses
      a computationally intensive, stochastic, spatial model to simulate multiple
      outbreaks and to determine appropriate sentinel locations for UK apiaries. Both
      models quantify the anticipated increase in success of sentinel sites as their
      number increases and as non-sentinel sites become worse at detection; however,
      unexpectedly sentinels perform relatively better for faster growing outbreaks.
      Additionally, the spatial model allows us to quantify the substantial role that
      carefully positioned sentinels can play in the rapid detection of exotic
      invasions.

PMID- 28446704
TI  - Preservation of protein expression systems at elevated temperatures for portable
      therapeutic production.
AB  - Many biotechnology capabilities are limited by stringent storage needs of
      reagents, largely prohibiting use outside of specialized laboratories. Focusing
      on a large class of protein-based biotechnology applications, we address this
      issue by developing a method for preserving cell-free protein expression systems
      for months above room temperature. Our approach realizes unprecedented long-term
      stability at elevated temperatures by leveraging the sugar alcohol trehalose, a
      simple, low-cost, open-air drying step, and strategic separation of reaction
      components during drying. The resulting preservation capacity enables efficient
      production of a wide range of on-demand proteins under adverse conditions, for
      instance during emergency outbreaks or in remote locations. To demonstrate
      application potential, we use cell-free reagents subjected to months of exposure
      at 37 degrees C and atmospheric conditions to produce sufficient concentrations
      of a pyocin protein to kill Pseudomonas aeruginosa, a troublesome pathogen for
      traumatic and burn wound injuries. Our work makes possible new biotechnology
      applications that demand ruggedness and scalability.

PMID- 28446706
TI  - A sister of NANOG regulates genes expressed in pre-implantation human
      development.
AB  - The NANOG homeobox gene plays a pivotal role in self-renewal and maintenance of
      pluripotency in human, mouse and other vertebrate embryonic stem cells, and in
      pluripotent cells of the blastocyst inner cell mass. There is a poorly studied
      and atypical homeobox locus close to the Nanog gene in some mammals which could
      conceivably be a cryptic paralogue of NANOG, even though the loci share only 20%
      homeodomain identity. Here we argue that this gene, NANOGNB (NANOG Neighbour), is
      an extremely divergent duplicate of NANOG that underwent radical sequence change
      in the mammalian lineage. Like NANOG, the NANOGNB gene is expressed in pre
      implantation embryos of human and cow; unlike NANOG, NANOGNB expression is
      restricted to 8-cell and morula stages, preceding blastocyst formation. When
      expressed ectopically in adult cells, human NANOGNB elicits gene expression
      changes, including downregulation of a set of genes that have an expression pulse
      at the 8-cell stage of pre-implantation development. We conclude that gene
      duplication and massive sequence divergence in mammals generated a novel homeobox
      gene that acquired new developmental roles complementary to those of Nanog.

PMID- 28446705
TI  - Diverse integrin adhesion stoichiometries caused by varied actomyosin activity.
AB  - Cells in an organism are subjected to numerous sources of external and internal
      forces, and are able to sense and respond to these forces. Integrin-mediated
      adhesion links the extracellular matrix outside cells to the cytoskeleton inside,
      and participates in sensing, transmitting and responding to forces. While
      integrin adhesion rapidly adapts to changes in forces in isolated migrating
      cells, it is not known whether similar or more complex responses occur within
      intact, developing tissues. Here, we studied changes in integrin adhesion
      composition upon different contractility conditions in Drosophila embryonic
      muscles. We discovered that all integrin adhesion components tested were still
      present at muscle attachment sites (MASs) when either cytoplasmic or muscle
      myosin II was genetically removed, suggesting a primary role of a developmental
      programme in the initial assembly of integrin adhesions. Contractility does,
      however, increase the levels of integrin adhesion components, suggesting a
      mechanism to balance the strength of muscle attachment to the force of muscle
      contraction. Perturbing contractility in distinct ways, by genetic removal of
      either cytoplasmic or muscle myosin II or eliminating muscle innervation, each
      caused unique alterations to the stoichiometry at MASs. This suggests that
      different integrin-associated proteins are added to counteract different kinds of
      force increase.

PMID- 28446707
TI  - Deterministic versus stochastic model of reprogramming: new evidence from
      cellular barcoding technique.
AB  - Factor-mediated reprogramming of somatic cells towards pluripotency is a low
      efficiency process during which only small subsets of cells are successfully
      reprogrammed. Previous analyses of the determinants of the reprogramming
      potential are based on average measurements across a large population of cells or
      on monitoring a relatively small number of single cells with live imaging. Here,
      we applied lentiviral genetic barcoding, a powerful tool enabling the
      identification of familiar relationships in thousands of cells. High-throughput
      sequencing of barcodes from successfully reprogrammed cells revealed a
      significant number of barcodes from related cells. We developed a computer model,
      according to which a probability of synchronous reprogramming of sister cells
      equals 10-30%. We conclude that the reprogramming success is pre-established in
      some particular cells and, being a heritable trait, can be maintained through
      cell division. Thus, reprogramming progresses in a deterministic manner, at least
      at the level of cell lineages.

PMID- 28446708
TI  - Structural and functional analysis of Oceanobacillus iheyensis macrodomain
      reveals a network of waters involved in substrate binding and catalysis.
AB  - Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose
      (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome
      inactivation, neurodegeneration and modulating PARP1 signalling, making them
      potential targets for therapeutic agents. Unfortunately, some aspects related to
      the substrate binding and catalysis of MacroD-like macrodomains still remain
      unclear, since mutation of the proposed catalytic aspartate does not completely
      abolish enzyme activity. Here, we present a functional and structural
      characterization of a macrodomain from the extremely halotolerant and
      alkaliphilic bacterium Oceanobacillus iheyensis (OiMacroD), related to
      hMacroD1/hMacroD2, shedding light on substrate binding and catalysis. The crystal
      structures of D40A, N30A and G37V mutants, and those with MES, ADPr and ADP
      bound, allowed us to identify five fixed water molecules that play a significant
      role in substrate binding. Closure of the beta6-alpha4 loop is revealed as
      essential not only for pyrophosphate recognition, but also for distal ribose
      orientation. In addition, a novel structural role for residue D40 is identified.
      Furthermore, it is revealed that OiMacroD not only catalyses the hydrolysis of O
      acetyl-ADP-ribose but also reverses protein mono-ADP-ribosylation. Finally,
      mutant G37V supports the participation of a substrate-coordinated water molecule
      in catalysis that helps to select the proper substrate conformation.

PMID- 28446709
TI  - Control of mitochondrial biogenesis and function by the ubiquitin-proteasome
      system.
AB  - Mitochondria are pivotal organelles in eukaryotic cells. The complex proteome of
      mitochondria comprises proteins that are encoded by nuclear and mitochondrial
      genomes. The biogenesis of mitochondrial proteins requires their transport in an
      unfolded state with a high risk of misfolding. The mislocalization of
      mitochondrial proteins is deleterious to the cell. The electron transport chain
      in mitochondria is a source of reactive oxygen species that damage proteins.
      Mitochondrial dysfunction is linked to many pathological conditions and, together
      with the loss of cellular protein homeostasis (proteostasis), are hallmarks of
      ageing and ageing-related degeneration diseases. The pathogenesis of
      neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease,
      has been associated with mitochondrial and proteostasis failure. Thus,
      mitochondrial proteins require sophisticated surveillance mechanisms. Although
      mitochondria form a proteasome-exclusive compartment, multiple lines of evidence
      indicate a crucial role for the cytosolic ubiquitin-proteasome system (UPS) in
      the quality control of mitochondrial proteins. The proteasome affects
      mitochondrial proteins at stages of their biogenesis and maturity. The effects of
      the UPS go beyond the removal of damaged proteins and include the adjustment of
      mitochondrial proteome composition, the regulation of organelle dynamics and the
      protection of cellular homeostasis against mitochondrial failure. In turn,
      mitochondrial activity and mitochondrial dysfunction adjust the activity of the
      UPS, with implications at the cellular level.

PMID- 28446710
TI  - Linear ubiquitin chains: enzymes, mechanisms and biology.
AB  - Ubiquitination is a versatile post-translational modification that regulates a
      multitude of cellular processes. Its versatility is based on the ability of
      ubiquitin to form multiple types of polyubiquitin chains, which are recognized by
      specific ubiquitin receptors to induce the required cellular response. Linear
      ubiquitin chains are linked through Met 1 and have been established as important
      players of inflammatory signalling and apoptotic cell death. These chains are
      generated by a ubiquitin E3 ligase complex called the linear ubiquitin chain
      assembly complex (LUBAC) that is thus far the only E3 ligase capable of forming
      linear ubiquitin chains. The complex consists of three subunits, HOIP, HOIL-1L
      and SHARPIN, each of which have specific roles in the observed biological
      functions of LUBAC. Furthermore, LUBAC has been found to be associated with
      OTULIN and CYLD, deubiquitinases that disassemble linear chains and
      counterbalance the E3 ligase activity of LUBAC. Gene mutations in HOIP, HOIL-1L
      and OTULIN are found in human patients who suffer from autoimmune diseases, and
      HOIL-1L mutations are also found in myopathy patients. In this paper, we discuss
      the mechanisms of linear ubiquitin chain generation and disassembly by their
      respective enzymes and review our current understanding of their biological
      functions and association with human diseases.

PMID- 28446711
TI  - Chemical roots of biological evolution: the origins of life as a process of
      development of autonomous functional systems.
AB  - In recent years, an extension of the Darwinian framework is being considered for
      the study of prebiotic chemical evolution, shifting the attention from
      homogeneous populations of naked molecular species to populations of
      heterogeneous, compartmentalized and functionally integrated assemblies of
      molecules. Several implications of this shift of perspective are analysed in this
      critical review, both in terms of the individual units, which require an adequate
      characterization as self-maintaining systems with an internal organization, and
      also in relation to their collective and long-term evolutionary dynamics, based
      on competition, collaboration and selection processes among those complex
      individuals. On these lines, a concrete proposal for the set of molecular control
      mechanisms that must be coupled to bring about autonomous functional systems, at
      the interface between chemistry and biology, is provided.

PMID- 28446712
TI  - Aspirin inhibits the SHH/GLI1 signaling pathway and sensitizes malignant glioma
      cells to temozolomide therapy.
AB  - Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1
      (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma
      cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's
      antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the
      feasibility of aspirin combined with TMZ therapy. Western blot and quantitative
      real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the
      SHH/GLI1 pathway was strongly inhibited by aspirin. Aspirin acted as the glioma
      growth-inhibitory and pro-apoptosis roles by inhibiting the SHH/GLI1 pathway and
      reprogramming the epithelial to mesenchymal transition (EMT). The
      immunofluorescence assay showed aspirin could prevent the nuclear translocation
      of GLI1 to inhibit its transcriptional regulation. The stable lentiviral
      overexpression of GLI1 reversed the DNA double strand breaks (DSBs) caused by the
      GANT61 and TMZ. Furthermore, aspirin combined with TMZ enhanced chemosensitivity
      and GLI1-induced chemoprotection was partly blocked by aspirin in vitro and in
      vivo. Collectively, aspirin has a therapeutic potential for SHH/GLI1 targeted
      therapy against glioma cells. Acquired activation of GLI1 protects glioma cells
      against TMZ therapy. Impairment of DNA DSBs repair activity might be involved in
      the route of aspirin-induced chemosensitivity. Combined aspirin with TMZ may be a
      promising strategy against malignant glioma.

PMID- 28446725
TI  - Comprehensive analysis of interleukin-8 gene polymorphisms and periodontitis
      susceptibility.
AB  - BACKGROUND: Associations between interleukin-8 (IL-8) gene polymorphisms and
      periodontitis susceptibility have been investigated in many published studies,
      but the conclusions are still inconsistent. Therefore, we performed this
      systematic review and meta-analysis to review which polymorphisms have been
      researched and to obtain a precise result of the same polymorphism from different
      studies. RESULTS: Finally 10 publications involving 1938 patients and 1569
      controls were yielded, including 12 polymorphisms. Six studies investigated
      rs4073 polymorphism; two focused on rs2227306 and rs2227307; two referred to
      rs2227532 and T-738A; one detected rs2230054, rs1126579 and rs1126580; one
      inspected A2767T, T11722T2 and C1633T, and one for rs2234671 polymorphism. Of
      them, IL-8 C1633T and rs1126580 polymorphisms showed positive association while
      the other ten polymorphisms revealed negative results. MATERIALS AND METHODS: A
      comprehensive literature search from PubMed, Web of Science, and Chinese National
      Knowledge Infrastructure was conducted for all potentially relevant studies
      published before January 2, 2017. Two authors selected the studies and extracted
      data. The pooled analysis was conducted using the RevMan 5.1 software if a
      polymorphism was reported by two or more studies. CONCLUSIONS: Based on current
      evidence, the IL-8 rs4073, A2767T, T11722T2, rs2234671, rs2230054, rs1126579,
      rs2227306, rs2227307, rs2227532, and T-738A polymorphisms were not associated
      with periodontitis susceptibility; the IL-8 C1633T and rs1126580 polymorphisms
      were associated with increased risk of periodontitis.

PMID- 28446729
TI  - WP1130 attenuates cisplatin resistance by decreasing P53 expression in non-small
      cell lung carcinomas.
AB  - Cisplatin-based combination chemotherapy significantly improves the survival
      outcomes in non-small cell lung carcinomas (NSCLCs), but drug resistance commonly
      contributes to disease progression and relapse. Recently, accumulating evidence
      has indicated that deubiquitinases (DUBs) are involved in regulating tumor cell
      proliferation, apoptosis, and chemoresistance. We designed this study to
      investigate the role of WP1130, a DUB inhibitor, in regulating cisplatin
      cytotoxicity in NSCLCs. After being combined with WP1130, cisplatin sensitivity
      was significantly increased in A549 and HCC827 cells with decreased p53
      expression, inhibiting their proliferation, but not in p53-deficient NCI-H1299
      cells. The synergistic cytotoxicity of the cisplatin and WP1130 co-treatment was
      abolished in p53-knockdown cells. Western blotting verified the decreased p53
      expression in A549 and HCC827 cells treated with cisplatin and WP1130. The
      administration of MG132, a proteasome inhibitor, or knockdown of ubiquitin
      specific peptidase 9, X-linked (USP9X) both eliminated the effect of WP1130 in
      decreasing p53 expression. Taken together, our findings confirm that the
      inclusion of WP1130 is potentially contributes to better therapeutic effects of
      cisplatin-based chemotherapy of NSCLCs in a manner dependent on the USP9X-p53
      ubiquitination-mediated degradation pathway.

PMID- 28446733
TI  - [33 Questions about Triglycerides and Cardiovascular Effects: Expert Answers].

PMID- 28446734
TI  - Iron deficiency and anemia in heart failure.
AB  - Heart failure is an important community health problem. Prevalence and incidence
      of heart failure have continued to rise over the years. Despite recent advances
      in heart failure therapy, prognosis is still poor, rehospitalization rate is very
      high, and quality of life is worse. Co-morbidities in heart failure have negative
      impact on clinical course of the disease, further impair prognosis, and add
      difficulties to treatment of clinical picture. Therefore, successful management
      of co-morbidities is strongly recommended in addition to conventional therapy for
      heart failure. One of the most common co-morbidities in heart failure is presence
      of iron deficiency and anemia. Current evidence suggests that iron deficiency and
      anemia are more prevalent in patients with heart failure and reduced ejection
      fraction, as well as those with heart failure and preserved ejection fraction.
      Moreover, iron deficiency and anemia are referred to as independent predictors
      for poor prognosis in heart failure. There is strong relationship between iron
      deficiency or anemia and severity of clinical status of heart failure. Over the
      last two decades, many clinical investigations have been conducted on clinical
      effectiveness of treatment of iron deficiency or anemia with oral iron,
      intravenous iron, and erythropoietin therapies. Studies with oral iron and
      erythropoietin therapies did not provide any clinical benefit and, in fact, these
      therapies have been shown to be associated with increase in adverse clinical
      outcomes. However, clinical trials in patients with iron deficiency in the
      presence or absence of anemia have demonstrated considerable clinical benefits of
      intravenous iron therapy, and based on these positive outcomes, iron deficiency
      has become target of therapy in management of heart failure. The present report
      assesses current approaches to iron deficiency and anemia in heart failure in
      light of recent evidence.

PMID- 28446726
TI  - Low concentration of BPA induces mice spermatocytes apoptosis via GPR30.
AB  - Bisphenol A (BPA) acts as xenoestrogen and has a great impact on disorders of
      human reproductive system. However, the mechanism through which BPA can affect
      human testicular function remains to be identified. GPR30 is a novel membrane
      estrogen receptor with high-affinity and low-capacity binding to estrogens. We
      demonstrated that estrogen receptor alpha (ERalpha), estrogen receptor beta
      (ERbeta) as well as GPR30 are expressed in mouse spermatocyte-derived GC-2 cells
      using Real-time PCR. We treated the cells with different doses of BPA and found
      that even low doses of BPA can inhibit GC-2 cell growth using MTT assay. To make
      sure which receptor is responsible for the biological function of BPA, we used ER
      down-regulator ICI and indicated that BPA could bind to GPR30. We also observed
      that BPA was able to induce Erk1/2 phosphorylation in GC-2 cells and proved that
      this process was mediated by GPR30-related EGFR-MAPK pathway using western blot.
      By Real-time PCR, we found that the expression of c-Fos was up-regulated and
      Cyclin D1 gene was down-regulated, in the presence of BPA and ICI. The results of
      MTT assay, comet assay and flow cytometry indicated that the activation of GPR30
      induced by BPA inhibited the cell growth and induced cell apoptosis and ICI,
      GPR30 siRNA, EGFR inhibitor (AG), and MAPK (PD) inhibitor could partially reverse
      this effect. Immunohistochemistry on the testis of BPA -damaged mice showed that
      BPA induced spermatocyte apoptosis without affecting the seminiferous tubules and
      spermatocyte. In conclusion, BPA triggered spermatocyte apoptosis via GPR30.

PMID- 28446735
TI  - The intention to leave among nurses: the role of job satisfaction, self-efficacy
      and work engagement.
AB  - INTRODUCTION: Retaining nursing staff within hospitals is essential to limit the
      negative impact of excessive voluntary turnover on the quality of care and
      organization costs. OBJECTIVES: The purpose of this study is to explain voluntary
      turnover in the nursing profession by analyzing the influence of job satisfaction
      and, in particular, self-efficacy and work engagement on turnover intention.
      METHODS: 210 nurses working in three hospitals in Southern Italy have completed a
      self-report questionnaire. A correlation analysis was applied in order to test
      the relationship between variables, while the role of age, professional and
      organizational seniority was estimated through partial correlations. A multiple
      linear regression was performed to verify the role of self-efficacy and work
      engagement in predicting turnover intention. RESULTS: Job satisfaction, self
      efficacy and work engagement are positively correlated. These dimensions are
      negatively correlated with the intention to change the hospital; furthermore,
      age, professional and organizational seniority have an effect on this
      relationship. Work engagement fully mediates the relationship between self
      efficacy and turnover intention. CONCLUSIONS: Results highlight the importance of
      considering not only job satisfaction, but also self-efficacy and work
      engagement, in studies on turnover intentions. These findings suggest to
      implement actions to increase self-efficacy, and especially work engagement, to
      reduce the voluntary turnover of nursing staff.

PMID- 28446736
TI  - Violating organizational and social norms in the workplace: a correlational study
      in the nursing context.
AB  - OBJECTIVES: The aim of this study was to examine, in a sample of nurses, the
      relationships between the organizational context variables (i.e., workload,
      interpersonal conflicts, organizational constraints), the burnout, the moral
      disengagement, and the counterproductive work behaviors (CWB), within their
      clinical work settings. METHODS: A descriptive, correlational study was conducted
      in a sample of 347 nurses working in different clinical settings in a big
      university hospital in Central Italy. A self-report questionnaire was used for
      data collection, using several scales to assess different variables related to
      the organisational context, the burnout, the interpersonal strain, the moral
      disengagement, and the CWB. RESULTS: The clinical context was found to influence
      nurses' organizational wellbeing, which in turn was found to foster CWB. Nurses
      working in outpatients settings and in day hospitals were those who reported the
      lowest CWB, in comparison with nurses working in the Emergency Department and in
      the General Medicine Units. CONCLUSIONS: Findings of this study are important for
      nursing professional chiefs and for any professional involved in the promotion of
      workers' wellbeing. Our study findings highlight how the clinical work setting
      and the organizational context variables can lead to CWB. Researchers and
      managers should keep these aspects in high consideration due to their influence
      on the quality of the care delivered.

PMID- 28446737
TI  - Pleural mesothelioma in doll manufacture: possible asbestos exposure.
AB  - BACKGROUND: The occurrence of malignant mesothelioma is almost always causally
      associated to asbestos exposure but, considering women occurrences, this
      association is often difficult to demonstrate and consequently the asbestos
      exposure is defined as 'unknown'. OBJECTIVES: To describe the working activity
      and to give occupational asbestos exposure probability estimation related to an
      uncommon and poorly investigated productive sector: doll manufacture. METHODS:
      From the Province of Brescia Mesothelioma Registry, established in 1993 on
      population-based criteria, we have extracted the certified mesothelioma diagnosis
      cases, related to patients who were employed for some time in doll manufacture.
      RESULTS: Among the 757 total cases of malignant mesothelioma registered and
      studied up to 2016, we found 3 cases of pleural epithelial mesothelioma
      histologically diagnosed in young women who had worked in two doll manufacturing
      companies and whose asbestos exposure had been initially defined as 'unknown',
      because an environmental, family or extra-professional asbestos exposure was
      considered unlikely. However, the judicial autopsy performed on one of the 3
      women had allowed examining lung tissue samples with Scanning Electron
      Microscopy. This technique showed a concentration of amphiboles fibers of about
      12,000,000 per gram of dry lung tissue, with a consequent re-classification of
      asbestos exposure from 'unknown' to 'occupational certified'. DISCUSSION:
      Mesotheliomas in women with no apparent occupational asbestos exposure are
      normally referred to life or family environmental exposure. Moreover, it is known
      that occupational asbestos exposure in women is difficult to recognize.
      Previously, only one publication had reported two cases of mesothelioma in cloth
      doll manufacture. The occurrence of two mesothelioma cases in the same company
      out of the three here presented was suggesting an occupational exposure. The
      finding of a high amphibole fibers lung concentration confirmed the previous
      hypothesis, despite the impossibility to determine the circumstances with good
      evidence. CONCLUSION: The three cases of mesothelioma in doll production workers
      suggest that also in this restricted manufacturing sector had occurred an
      occupational asbestos exposure, which is up to now unknown and isn't due only to
      the use of sewing or ironing machines. The lung asbestos fibers burden analysis
      is confirmed to be a decisive factor in the assessment of mesothelioma cases with
      'unknown' exposure.

PMID- 28446738
TI  - Work activity and phenylalanine levels in a population of young adults with
      classic PKU.
AB  - BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism characterized
      by increased blood concentrations of phenylalanine (Phe). OBJECTIVES: The aim of
      the present study was to assess the association between the metabolic compliance
      of adult patients affected by classic PKU and the characteristics of their
      present and past occupations. METHODS: The study population consisted of working
      adults, affected by classic PKU, and following a dietary treatment. Univariate
      linear-mixed models and multivariate analysis were applied to assess the
      association between Phe blood levels and individual covariates: age, sex, time at
      diagnosis, educational level and work characteristics. RESULTS: A linear
      relationship was found with age (an average annual increase of 30.56 MUMol/L
      (C.I. 95%: 7.53; 53.60) in the mean Phe blood levels). Full-time work appeared to
      be associated with a worse metabolic compliance when compared to part-time work
      (mean Phe blood levels >281.11 MUMol/L). Shift work was related to a worse
      metabolic compliance, with mean Phe plasmatic levels >356.73 MUMol/L.
      CONCLUSIONS: Our data suggests that work may influence the metabolic compliance
      in adults with PKU. In particular, a part-time employment could allow for a
      better metabolic compliance, while daily work should be preferred to shift work.

PMID- 28446739
TI  - Suspected cutaneous leishmaniasis in a sample of Westerns Sicily residents: what
      correlation with occupation?
AB  - BACKGROUND: Leishmaniasis is a widespread infectious disease, but there is not
      much information about its prevalence in high risk occupational categories.
      OBJECTIVES: The aim of this study is to assess the prevalence of Leishmania
      immunological positivity in human skin tissues collected from subjects living in
      Western Sicily, with suspected cutaneous Leishmania infection, in order to
      explore the risk possibly related to occupation. METHODS: 318 consecutive
      subjects (M/F ratio=1.0, mean age=40+/-25.4 years), attending the Dermatology
      Department of the University of Palermo Hospital from 2013 to 2015, without any
      previous history of Leishmania infection and performing various occupations, were
      included. Parasite isolation and PCR-RT test on skin scrapings were performed to
      evaluate the immunological status; all data were analyzed by the chi square test,
      comparing all positive results from the different provinces. RESULTS: 81 (50.9%)
      out of 159 females and 79 (49.7%) out of 159 males were found PCR-RT positive to
      Leishmania infantum, with a higher risk in the Agrigento district (p<0.001) and
      in subjects living in rural areas (p=0.0038), regardless of the type of work
      performed. The observed animal leishmaniasis prevalence in the same areas shows
      the endemic status of the disease in Sicily. CONCLUSIONS: Although based on a
      relatively small sample, our study shows that cutaneous leishmaniasis represents
      a health care problem with a medical and social impact in Western Sicily. An
      active surveillance system and the establishment of diagnosis and treatment
      centres could be useful in controlling this public health problem.

PMID- 28446740
TI  - Biological risk among agriculture and construction workers in Molise Region,
      Central Italy.
AB  - BACKGROUND: Biological risk is a significant issue in workplaces due to
      continuous modification of work organization and condition. OBJECTIVES: In this
      pilot study, perception and knowledge of biological risk, as well as adoption of
      prevention measures were evaluated among construction and agriculture workers.
      METHODS: A structured questionnaire was administered to workers to collect socio
      demographic and employment information, in addition to data on risk perception
      and knowledge, and adoption of preventive measures, including those related to
      work activities. RESULTS: Fifty-three workers aged 45.3+/-9.8 years participated
      in the study, 81% were male, and 70% were construction workers. Approximately 80%
      of participants declared that infectious diseases are neither frequent nor health
      threatening in their occupational activity. The majority of workers considered
      some diseases, such as hepatitis A and B, leptospirosis and listeriosis, as
      posing a low risk to their health. Forty-seven % claimed to be unexposed to
      biohazards at their workplace, and 72% were not worried about them. Ninety-six %
      of the workers knew about vaccination for tetanus, but only 74% and 36% knew
      about the availability of vaccination for Hepatitis A and B, respectively. During
      lifetime, 94% of the workers received at least one vaccination. All workers had
      undergone tetanus vaccination, but only few received vaccine for influenza,
      hepatitis B and tuberculosis. CONCLUSIONS: This pilot study in occupational
      settings revealed a poor perception of biological risk and a limited awareness of
      the severity of infectious diseases. Major knowledge gaps existed about the
      available preventive measures. It is essential to promote safety culture at the
      workplace also with regard to biological hazards. This requires improving
      information and education, conducting appropriate studies, and prompting health
      and safety professional actors to focus on occupational infectious disease
      problems.

PMID- 28446741
TI  - Methodology to define biological reference values in the environmental and
      occupational fields: the contribution of the Italian Society for Reference Values
      (SIVR).
AB  - BACKGROUND: Biological reference values (RVs) explore the relationships between
      humans and their environment and habits. RVs are fundamental in the environmental
      field for assessing illnesses possibly associated with environmental pollution,
      and also in the occupational field, especially in the absence of established
      biological or environmental limits. OBJECTIVES: The Italian Society for Reference
      Values (SIVR) determined to test criteria and procedures for the definition of
      RVs to be used in the environmental and occupational fields. METHODS: The paper
      describes the SIVR methodology for defining RVs of xenobiotics and their
      metabolites. Aspects regarding the choice of population sample, the quality of
      analytical data, statistical analysis and control of variability factors are
      considered. The simultaneous interlaboratory circuits involved can be expected to
      increasingly improve the quality of the analytical data. RESULTS: Examples of RVs
      produced by SIVR are presented. In particular, levels of chromium, mercury,
      ethylenethiourea, 3,5,6-trichloro-2-pyridinol, 2,5-hexanedione, 1-hydroxypyrene
      and t,t-muconic acid measured in urine and expressed in micrograms/g creatinine
      (MUg/g creat) or micrograms/L (MUg/L) are reported. CONCLUSIONS: With the
      proposed procedure, SIVR intends to make its activities known to the scientific
      community in order to increase the number of laboratories involved in the
      definition of RVs for the Italian population. More research is needed to obtain
      further RVs in different biological matrices, such as hair, nails and exhaled
      breath. It is also necessary to update and improve the present reference values
      and broaden the portfolio of chemicals for which RVs are available. In the near
      future, SIVR intends to expand its scientific activity by using a multivariate
      approach for xenobiotics that may have a common origin, and to define RVs
      separately for children who may be exposed more than adults and be more
      vulnerable.

PMID- 28446742
TI  - Work and health care in Milan, 1864-1874.
AB  - In 1864 in Milan, Giovanni Rosmini (1832-1896) opened an ophthalmic dispensary
      for workers. In 1874 this dispensary was transformed into the first ophthalmic
      hospital of the city. This hospital still exists today. The authors analyze a
      document that belonged to the lawyer Enrico Rosmini (1828-1898), brother of
      Giovanni, which helps to piece together the early years of the dispensary, where
      about 4,000 surgeries were carried out in the first four years of activity. This
      historical document is valuable as it sheds light on one of the first healthcare
      institution for workers in Milan.

PMID- 28446744
TI  - Levetiracetam Pharmacokinetics in a Patient with Intracranial Hemorrhage
      Undergoing Continuous Veno-Venous Hemofiltration.
AB  - BACKGROUND Levetiracetam is an antiepileptic drug frequently used in critically
      ill patients. Levetiracetam is primarily eliminated as a parent compound via
      glomerular filtration and requires dose adjustment in renal insufficiency, but
      the literature on patients receiving continuous veno-venous hemofiltration (CVVH)
      is scant. CASE REPORT We report the levetiracetam pharmacokinetic profile of a
      patient being treated with levetiracetam 1000 mg intravenously every 12 h who
      required continuous veno-venous hemofiltration (CVVH). The patient underwent CVVH
      utilizing a high-flux polyethersulfone membrane filter. The blood flow rate was
      250 ml/min, and the predilution replacement therapy fluid flow rate was 2000
      ml/h. After achieving presumed steady-state on levetiracetam 1000 mg q12h, serial
      plasma samples (pre- and post-filter) and effluent samples were drawn at 2, 4, 6,
      8, and 10 h. Levetiracetam concentrations were determined utilizing LC-MS/MS. The
      levetiracetam maximum concentration (Cmax), minimum concentration (Cmin), half
      life, area under the concentration-time curve (AUC0-12), clearance (CL), and
      volume of distribution (Vd) were 30.7 ug/ml, 16.1 ug/ml, 12.9 h, 272 mg.hr/L,
      3.68 L/h, and 0.73 L/kg, respectively. The sieving coefficient was 1.03+/-0.08.
      CVVH represented 61.3% of the total levetiracetam clearance. The patient was
      maintained on CVVH for 24 consecutive days and then transitioned to intermittent
      hemodialysis and remained seizure-free. CONCLUSIONS CVVH is highly effective in
      removing levetiracetam from circulating plasma. Due to the effective removal,
      standard doses of levetiracetam are required to maintain adequate plasma
      concentrations. Dose reductions utilizing HD or estimated creatinine clearance
      recommendations will likely lead to subtherapeutic levels, especially if higher
      CVVH flow rates are used.

PMID- 28446743
TI  - Mammalian Target of Rapamycin (mTOR) Regulates Transforming Growth Factor-beta1
      (TGF-beta1)-Induced Epithelial-Mesenchymal Transition via Decreased Pyruvate
      Kinase M2 (PKM2) Expression in Cervical Cancer Cells.
AB  - BACKGROUND Epithelial-mesenchymal transition (EMT) plays an important role in
      cancer tumorigenesis. Transforming growth factor beta1 (TGF-beta1) can induced
      EMT, which could increase tumor migration and invasion. Moreover, recent studies
      have been proven that mammalian target of rapamycin (mTOR) is a critical
      regulator of EMT. We investigated the mechanisms of mTOR in transforming growth
      factor beta1 (TGF-beta1)-induced EMT in cervical cancer cells. MATERIAL AND
      METHODS HeLa and SiHa cells were treated with 10 ng/ml TGF-beta1 to induce EMT.
      Then, they were treated with or without rapamycin. CCK8 assay was performed to
      determine cell proliferation. Cell migration was detected by wound-healing assay;
      apoptosis was analyzed by flow cytometry; mTOR inhibitors inhibited mTOR pathway
      to assess the expression of E-cadherin, Vimentin STAT3, Snail2, p-p70s6k, and
      PKM2 expression. RESULTS TGF-beta1 promoted proliferation and migration, and
      attenuated apoptosis in cervical carcinoma cells. Rapamycin abolished TGF-beta1
      induced EMT cell proliferation and migration and reversed TGF-beta1-induced EMT.
      E-cadherin were suppressed, whereas Vimentin and PKM2 were increased in HeLa and
      SiHa cells after stimulation with TGF-beta1. Moreover, mTOR was activated in the
      process of TGF-beta1-induced EMT. Rapamycin inhibited the phosphorylation of
      p70s6k. Furthermore, inhibition of the mTOR pathway decreased PKM2 expression.
      CONCLUSIONS Inhibition of the mTOR pathway abolished TGF-beta1-induced EMT and
      reduced mTOR/p70s6k signaling, which downregulated PKM2 expression. Our results
      provide novel mechanistic insight into the anti-tumor effects of inhibition of
      mTOR.

PMID- 28446745
TI  - Near band gap luminescence in hybrid organic-inorganic structures based on
      sputtered GaN nanorods.
AB  - Novel hybrid organic-inorganic nanostructures fabricated to utilize non-radiative
      resonant energy transfer mechanism are considered to be extremely attractive for
      a variety of light emitters for down converting of ultaviolet light and for
      photovoltaic applications since they can be much more efficient compared to
      devices grown with common design. Organic-inorganic hybrid structures based on
      green polyfluorene (F8BT) and GaN (0001) nanorods grown by magnetron sputtering
      on Si (111) substrates are studied. In such nanorods, stacking faults can form
      periodic polymorphic quantum wells characterized by bright luminescence. In
      difference to GaN exciton emission, the recombination rate for the stacking fault
      related emission increases in the presence of polyfluorene film, which can be
      understood in terms of Forster interaction mechanism. From comparison of dynamic
      properties of the stacking fault related luminescence in the hybrid structures
      and in the bare GaN nanorods, the pumping efficiency of non-radiative resonant
      energy transfer in hybrids was estimated to be as high as 35% at low
      temperatures.

PMID- 28446746
TI  - Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post
      stroke blood brain barrier disruption.
AB  - Our group recently identified 16 genes whose peripheral blood expression levels
      are differentially regulated in acute ischemic stroke. The purpose of this study
      was to determine whether the early expression levels of any of these 16 genes are
      predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional
      expression levels of candidate genes were measured in peripheral blood sampled
      from ischemic stroke patients at emergency department admission, and BBB
      permeability was assessed at 24 hour follow up via perfusion-weighted imaging.
      Early heightened expression levels of AKAP7, a gene encoding a protein kinase A
      binding scaffolding molecule, were significantly associated with BBB disruption
      24 hours post-hospital admission. We then determined that AKAP7 is predominantly
      expressed by lymphocytes in peripheral blood, and strongly co-expressed with
      ITGA3, a gene encoding the adhesion molecule integrin alpha 3. Subsequent in
      vitro experiments revealed that heightened expression of AKAP7 and ITGA3 in
      primary human lymphocytes is associated with a highly adherent phenotype.
      Collectively, our results suggest that AKAP7 expression levels may have clinical
      utility as a prognostic biomarker for post-stroke BBB complications, and are
      likely elevated early in patients who later develop post-stroke BBB disruption
      due to the presence of an invasive lymphocyte population in the peripheral blood.

PMID- 28446747
TI  - A Systems Pharmacology Approach to Determine Active Compounds and Action
      Mechanisms of Xipayi KuiJie'an enema for Treatment of Ulcerative colitis.
AB  - Xipayi Kui Jie'an (KJA), a type of traditional Uygur medicine (TUM), has shown
      promising therapeutic effects in Ulcerative colitis (UC). Owing to the complexity
      of TUM, the pharmacological mechanism of KJA remains vague. Therefore, the
      identification of complex molecular mechanisms is a major challenge and a new
      method is urgently needed to address this problem. In this study, we established
      a feasible pharmacological model based on systems pharmacology to identify
      potential compounds and targets. We also applied compound-target and target
      diseases network analysis to evaluate the action mechanisms. According to the
      predicted results, 12 active compounds were selected and these compounds were
      also identified by HPLC-ESI-MS/MS analysis. The main components were tannins,
      this result is consistent with the prediction. The active compounds interacted
      with 22 targets. Two targets including PTGS2 and PPARG were demonstrated to be
      the main targets associated with UC. Systematic analysis of the constructed
      networks revealed that these targets were mainly involved in NF-kappaB signaling
      pathway. Furthermore, KJA could also regulate the CD4 + CD25 + Foxp3 + Treg
      cells. In conclusion, this systems pharmacology-based approach not only explained
      that KJA could alleviate the UC by regulating its candidate targets, but also
      gave new insights into the potential novel therapeutic strategies for UC.

PMID- 28446748
TI  - Discovering charge density functionals and structure-property relationships with
      PROPhet: A general framework for coupling machine learning and first-principles
      methods.
AB  - Modern ab initio methods have rapidly increased our understanding of solid state
      materials properties, chemical reactions, and the quantum interactions between
      atoms. However, poor scaling often renders direct ab initio calculations
      intractable for large or complex systems. There are two obvious avenues through
      which to remedy this problem: (i) develop new, less expensive methods to
      calculate system properties, or (ii) make existing methods faster. This paper
      describes an open source framework designed to pursue both of these avenues.
      PROPhet (short for PROPerty Prophet) utilizes machine learning techniques to find
      complex, non-linear mappings between sets of material or system properties. The
      result is a single code capable of learning analytical potentials, non-linear
      density functionals, and other structure-property or property-property
      relationships. These capabilities enable highly accurate mesoscopic simulations,
      facilitate computation of expensive properties, and enable the development of
      predictive models for systematic materials design and optimization. This work
      explores the coupling of machine learning to ab initio methods through means both
      familiar (e.g., the creation of various potentials and energy functionals) and
      less familiar (e.g., the creation of density functionals for arbitrary
      properties), serving both to demonstrate PROPhet's ability to create exciting
      post-processing analysis tools and to open the door to improving ab initio
      methods themselves with these powerful machine learning techniques.

PMID- 28446749
TI  - Dynamics of chromatin accessibility during TGF-beta-induced EMT of Ras
      transformed mammary gland epithelial cells.
AB  - Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor
      (TGF)-beta and facilitates tumor progression. We here performed global mapping of
      accessible chromatin in the mouse mammary gland epithelial EpH4 cell line and its
      Ras-transformed derivative (EpRas) using formaldehyde-assisted isolation of
      regulatory element (FAIRE)-sequencing. TGF-beta and Ras altered chromatin
      accessibility either cooperatively or independently, and AP1, ETS, and RUNX
      binding motifs were enriched in the accessible chromatin regions of EpH4 and
      EpRas cells. Etv4, an ETS family oncogenic transcription factor, was strongly
      expressed and bound to more than one-third of the accessible chromatin regions in
      EpRas cells treated with TGF-beta. While knockdown of Etv4 and another ETS family
      member Etv5 showed limited effects on the decrease in the E-cadherin abundance
      and stress fiber formation by TGF-beta, gene ontology analysis showed that genes
      encoding extracellular proteins were most strongly down-regulated by Etv4 and
      Etv5 siRNAs. Accordingly, TGF-beta-induced expression of Mmp13 and cell
      invasiveness were suppressed by Etv4 and Etv5 siRNAs, which were accompanied by
      the reduced chromatin accessibility at an enhancer region of Mmp13 gene. These
      findings suggest a mechanism of transcriptional regulation during Ras- and TGF
      beta-induced EMT that involves alterations of accessible chromatin, which are
      partly regulated by Etv4 and Etv5.

PMID- 28446750
TI  - Expandable Mg-based Helical Stent Assessment using Static, Dynamic, and Porcine
      Ex Vivo Models.
AB  - A bioresorbable metallic helical stent was explored as a new device opportunity
      (magnesium scaffold), which can be absorbed by the body without leaving a trace
      and simultaneously allowing restoration of vasoreactivity with the potential for
      vessel remodeling. In this study, developed Mg-based helical stent was inserted
      and expanded in vessels with subsequent degradation in various environments
      including static, dynamic, and porcine ex vivo models. By assessing stent
      degradation in three different environments, we observed: (1) stress- and flow
      induced degradation; (2) a high degradation rate in the dynamic reactor; (3)
      production of intermediate products (MgO/Mg(OH)2 and Ca/P) during degradation;
      and (4) intermediate micro-gas pocket formation in the neighboring tissue ex vivo
      model. Overall, the expandable Mg-based helical stent employed as a scaffold
      performed well, with expansion rate (>100%) in porcine ex vivo model.

PMID- 28446751
TI  - CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle
      progression in human osteosarcoma cells.
AB  - Cell cycle progression in mammals is strictly controlled by a number of cyclin
      dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is
      often dysregulated in cancer cells. Our previous work revealed that Cullin 4B
      (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is
      overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we
      demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA
      damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in
      human osteosarcoma cells. In vitro and in vivo ubiquitination analyses indicated
      that CRL4BDCAF11 E3 ligase was able to specifically ubiquitinate a CDK inhibitor
      p21Cip1 at K16, K154, K161 and K163 but not at K75 and K141. Knocking down any
      component of the CRL4BDCAF11 complex, including CUL4B, DDB1 or DCAF11, using
      short hairpin RNAs (shRNAs) attenuated the ubiquitination level of p21Cip1,
      inhibited osteosarcoma cell proliferation, led to cell cycle arrest at S phase,
      and decreased colony formation rate. Taken together, our data suggest that the
      CRL4BDCAF11 complex represents a unique E3 ligase that promotes the
      ubiquitination of p21Cip1 and regulates cell cycle progression in human
      osteosarcoma cells.

PMID- 28446752
TI  - Near-atomic structure of Japanese encephalitis virus reveals critical
      determinants of virulence and stability.
AB  - Although several different flaviviruses may cause encephalitis, Japanese
      encephalitis virus is the most significant, being responsible for thousands of
      deaths each year in Asia. The structural and molecular basis of this encephalitis
      is not fully understood. Here, we report the cryo-electron microscopy structure
      of mature Japanese encephalitis virus at near-atomic resolution, which reveals an
      unusual "hole" on the surface, surrounded by five encephalitic-specific motifs
      implicated in receptor binding. Glu138 of E, which is highly conserved in
      encephalitic flaviviruses, maps onto one of these motifs and is essential for
      binding to neuroblastoma cells, with the E138K mutation abrogating the
      neurovirulence and neuroinvasiveness of Japanese encephalitis virus in mice. We
      also identify structural elements modulating viral stability, notably Gln264 of
      E, which, when replaced by His264 strengthens a hydrogen-bonding network, leading
      to a more stable virus. These studies unveil determinants of neurovirulence and
      stability in Japanese encephalitis virus, opening up new avenues for therapeutic
      interventions against neurotropic flaviviruses.Japanese encephalitis virus (JEV)
      is a Flavivirus responsible for thousands of deaths every year for which there
      are no specific anti-virals. Here, Wang et al. report the cryo-EM structure of
      mature JEV at near-atomic resolution and identify structural elements that
      modulate stability and virulence.

PMID- 28446754
TI  - Phonon-mediated repulsion, sharp transitions and (quasi)self-trapping in the
      extended Peierls-Hubbard model.
AB  - We study two identical fermions, or two hard-core bosons, in an infinite chain
      and coupled to phonons by interactions that modulate their hopping as described
      by the Peierls/Su-Schrieffer-Heeger (SSH) model. We show that exchange of phonons
      generates effective nearest-neighbor repulsion between particles and also gives
      rise to interactions that move the pair as a whole. The two-polaron phase diagram
      exhibits two sharp transitions, leading to light dimers at strong coupling and
      the flattening of the dimer dispersion at some critical values of the parameters.
      This dimer (quasi)self-trapping occurs at coupling strengths where single
      polarons are mobile. This illustrates that, depending on the strength of the
      phonon-mediated interactions, the coupling to phonons may completely suppress or
      strongly enhance quantum transport of correlated particles.

PMID- 28446753
TI  - Histamine and Histamine H4 Receptor Promotes Osteoclastogenesis in Rheumatoid
      Arthritis.
AB  - Histamine H4 receptor (H4R) has immune-modulatory and chemotaxic effects in
      various immune cells. This study aimed to determine the osteoclastogenic role of
      H4R in rheumatoid arthritis (RA). The concentration of histamine in synovial
      fluid (SF) and sera in patients with RA was measured using ELISA. After RA SF and
      peripheral blood (PB) CD14+ monocytes were treated with histamine, IL-17, IL-21
      and IL-22, and a H4R antagonist (JNJ7777120), the gene expression H4R and RANKL
      was determined by real-time PCR. Osteoclastogenesis was assessed by counting TRAP
      positive multinucleated cells in PB CD14+ monocytes cultured with histamine, Th17
      cytokines and JNJ7777120. SF and serum concentration of histamine was higher in
      RA, compared with osteoarthritis and healthy controls. The expression of H4R was
      increased in PB monocytes in RA patients. Histamine, IL-6, IL-17, IL-21 and IL-22
      induced the expression of H4R in monocytes. Histamine, IL-17, and IL-22
      stimulated RANKL expression in RA monocytes and JNJ7777120 reduced the RANKL
      expression. Histamine and Th17 cytokines induced the osteoclast differentiation
      from monocytes and JNJ7777120 decreased the osteoclastogenesis. H4R mediates
      RANKL expression and osteoclast differentiation induced by histamine and Th17
      cytokines. The blockage of H4R could be a new therapeutic modality for prevention
      of bone destruction in RA.

PMID- 28446755
TI  - Relationship between ion migration and interfacial degradation of CH3NH3PbI3
      perovskite solar cells under thermal conditions.
AB  - Organic-inorganic hybrid perovskite solar cells (PSCs) have been extensively
      studied because of their outstanding performance: a power conversion efficiency
      exceeding 22% has been achieved. The most commonly used PSCs consist of
      CH3NH3PbI3 (MAPbI3) with a hole-selective contact, such as 2,2',7,7'-tetrakis(N,N
      di-p-methoxyphenylamine)-9,9-spiro-bifluorene (spiro-OMeTAD), for collecting
      holes. From the perspective of long-term operation of solar cells, the cell
      performance and constituent layers (MAPbI3, spiro-OMeTAD, etc.) may be influenced
      by external conditions like temperature, light, etc. Herein, we report the
      effects of temperature on spiro-OMeTAD and the interface between MAPbI3 and spiro
      OMeTAD in a solar cell. It was confirmed that, at high temperatures (85  degrees
      C), I- and CH3NH3+ (MA+) diffused into the spiro-OMeTAD layer in the form of
      CH3NH3I (MAI). The diffused I- ions prevented oxidation of spiro-OMeTAD, thereby
      degrading the electrical properties of spiro-OMeTAD. Since ion diffusion can
      occur during outdoor operation, the structural design of PSCs must be considered
      to achieve long-term stability.

PMID- 28446756
TI  - A Chemically Patterned Microfluidic Paper-based Analytical Device (C-uPAD) for
      Point-of-Care Diagnostics.
AB  - A chemically patterned microfluidic paper-based analytical device (C-uPAD) is
      developed to create fluidic networks by forming hydrophobic barriers using
      chemical vapor deposition (CVD) of trichlorosilane (TCS) on a chromatography
      paper. By controlling temperature, pattern size, and CVD duration, optimal
      conditions were determined by characterizing hydrophobicity, spreading patterns,
      and flow behavior on various sized fluidic patterns. With these optimal
      conditions, we demonstrated glucose assay, immunoassay, and heavy metal detection
      on well-spot C-uPAD and lateral flow C-uPAD. For these assays, standard curves
      showing correlation between target concentration and gray intensity were obtained
      to determine a limit of detection (LOD) of each assay. For the glucose assays on
      both well-spot C-uPAD and lateral flow C-uPAD, we achieved LOD of 13 mg/dL, which
      is equivalent to that of a commercial glucose sensor. Similar results were
      obtained from tumor necrosis factor alpha (TNFalpha) detection with 3 ng/mL of
      LOD. For Ni detection, a colorimetric agent was immobilized to obtain a
      stationary and uniform reaction by using thermal condensation coupling method.
      During the immobilization, we successfully functionalized amine for coupling the
      colorimetric agent on the C-uPAD and detected as low as 150 MUg/L of Ni. These C
      uPADs enable simple, rapid, and cost-effective bioassays and environmental
      monitoring, which provide practically relevant LODs with high expandability and
      adaptability.

PMID- 28446757
TI  - Value of evidence from syndromic surveillance with cumulative evidence from
      multiple data streams with delayed reporting.
AB  - Delayed reporting of health data may hamper the early detection of infectious
      diseases in surveillance systems. Furthermore, combining multiple data streams,
      e.g. aiming at improving a system's sensitivity, can be challenging. In this
      study, we used a Bayesian framework where the result is presented as the value of
      evidence, i.e. the likelihood ratio for the evidence under outbreak versus
      baseline conditions. Based on a historical data set of routinely collected cattle
      mortality events, we evaluated outbreak detection performance (sensitivity, time
      to detection, in-control run length) under the Bayesian approach among three
      scenarios: presence of delayed data reporting, but not accounting for it;
      presence of delayed data reporting accounted for; and absence of delayed data
      reporting (i.e. an ideal system). Performance on larger and smaller outbreaks was
      compared with a classical approach, considering syndromes separately or combined.
      We found that the Bayesian approach performed better than the classical approach,
      especially for the smaller outbreaks. Furthermore, the Bayesian approach
      performed similarly well in the scenario where delayed reporting was accounted
      for to the scenario where it was absent. We argue that the value of evidence
      framework may be suitable for surveillance systems with multiple syndromes and
      delayed reporting of data.

PMID- 28446758
TI  - Irradiation-induced beta to alpha SiC transformation at low temperature.
AB  - We observed that beta-SiC, neutron irradiated to 9 dpa (displacements per atom)
      at ~1440  degrees C, began transforming to alpha-SiC, with radiation-induced
      Frank dislocation loops serving as the apparent nucleation sites. 1440  degrees C
      is a far lower temperature than usual beta -> alpha phase transformations in SiC.
      SiC is considered for applications in advanced nuclear systems, as well as for
      electronic or spintronic applications requiring ion irradiation processing. beta
      SiC, preferred for nuclear applications, is metastable and undergoes a phase
      transformation at high temperatures (typically 2000  degrees C and above).
      Nuclear reactor concepts are not expected to reach the very high temperatures for
      thermal transformation. However, our results indicate incipient beta -> alpha
      phase transformation, in the form of small (~5-10 nm) pockets of alpha-SiC
      forming in the beta matrix. In service transformation could degrade structural
      stability and fuel integrity for SiC-based materials operated in this regime.
      However, engineering this transformation deliberately using ion irradiation could
      enable new electronic applications.

PMID- 28446759
TI  - Transcriptomic response of durum wheat to nitrogen starvation.
AB  - Nitrogen (N) is a key macronutrient representing a limiting factor for plant
      growth and development and affects productivity in wheat. In this study, durum
      wheat response to N chronic starvation during grain filling was investigated
      through a transcriptomic approach in roots, leaves/stems, flag leaf and spikes of
      cv. Svevo. Nitrogen stress negatively influenced plant height, tillering, flag
      leaf area, spike and seed traits, and total N content. RNA-seq data revealed
      4,626 differentially expressed genes (DEGs). Most transcriptomic changes were
      observed in roots, with 3,270 DEGs, while 963 were found in leaves/stems, 470 in
      flag leaf, and 355 in spike tissues. A total of 799 gene ontology (GO) terms were
      identified, 180 and 619 among the upregulated and downregulated genes,
      respectively. Among the most addressed GO categories, N compound metabolism,
      carbon metabolism, and photosynthesis were mostly represented. Interesting DEGs,
      such as N transporters, genes involved in N assimilation, along with
      transcription factors, protein kinases and other genes related to stress were
      highlighted. These results provide valuable information about the transcriptomic
      response to chronic N stress in durum wheat, which could be useful for future
      improvement of N use efficiency.

PMID- 28446760
TI  - Genetic analysis of the TMEM230 gene in Chinese Han patients with Parkinson's
      disease.
AB  - TMEM230 mutations have been recently reported to cause autosomal dominant
      Parkinson's disease (PD). However, there are limited studies from different
      ethnic populations to support the role of TMEM230 in sporadic PD. In this study,
      we performed a comprehensive TMEM230 mutation screening in 550 sporadic PD
      patients and 560 controls to elaborate the genetic contribution of TMEM230 to
      sporadic PD. Overall, we did not find any pathogenic mutations in the coding
      sequence, while we identified four variants (c.68 + 182G > A, c.78A > G, c.552 +
      11A > G and c.174 + 11C > T) both in the patients and controls, and c.68 + 182G >
      A appeared to be associated with an increased risk of PD (odds ratio 1.782, 95%
      confidence interval 1.035-3.067, p < 0.05). After Bonferroni correction, however,
      c. 68 + 182G > A had no significant association with sporadic PD (p c = 0.136, p
      c > 0.05). Thus our results suggest that TMEM230 gene mutations may be rare in
      Chinese populations, and the variability of TMEM230 gene may not be a main factor
      for sporadic PD patients in Chinese Han populations. More evidence is still
      needed to clarify this question.

PMID- 28446761
TI  - Metabolic Syndrome Modulates Association between Endothelial Lipase and
      Lipid/Lipoprotein Plasma Levels in Acute Heart Failure Patients.
AB  - We hypothesised that the established association of endothelial lipase (EL)
      plasma levels with atherogenic lipid profile is altered in acute heart failure
      (AHF) and additionally affected by overlapping metabolic syndrome (MetS). We
      examined the association of EL plasma levels and lipid/lipoprotein plasma levels
      in AHF patients without and with overlapping MetS. The study was performed as a
      single-centre, observational study on 152 AHF patients, out of which 85 had
      overlapping MetS. In the no-MetS group, EL plasma levels were significantly
      positively correlated with plasma levels of atherogenic lipids/lipoproteins,
      including total cholesterol, low-density lipoprotein (LDL)-cholesterol, total LDL
      particles and triglycerides, but also with plasma levels of antiatherogenic high
      density lipoprotein (HDL)-cholesterol, total HDL particles and small HDL
      particles. In the MetS group, EL plasma levels were positively correlated with
      triglyceride and small LDL-particle levels, and significantly negatively
      correlated with plasma levels of large HDL particles as well as with LDL- and HDL
      particle size, respectively. EL- and lipid/lipoprotein- plasma levels were
      different in the no-MetS patients, compared to MetS patients. The association of
      EL with atherogenic lipid profile is altered in AHF and additionally modified by
      MetS, which strongly modulates EL- and lipid/lipoprotein-plasma levels in AHF.

PMID- 28446762
TI  - Dual-cavity feedback assisted DFB narrow linewidth laser.
AB  - Single longitudinal mode (SLM) distributed feedback (DFB) lasers with a linewidth
      lower than a few kHz find applications in many coherent detection systems. In
      this paper, we proposed and experimentally demonstrated a novel method to
      compress the linewidth of a SLM DFB laser by utilizing a dual-cavity feedback
      structure (DCFS). The DCFS first provides optical self-injection feedback to
      compress the laser linewidth, and then the two feedback lengths are carefully
      optimized to achieve SLM output via the Vernier principle and the suppression of
      modes overlapping between two cavities. The linewidthes of 1 MHz and 200 kHz were
      successfully compressed to ~2.7 and 1.5 kHz with a side mode suppression ratio of
      38 and 45 dB, respectively. The stability of the DCFS output power can be
      controlled within ~0.21%. Our method provides a simple, effective, low cost way
      to achieve DFB linewidth compression, which will greatly improve the performance
      of coherent detection systems using DFB laser as sources.

PMID- 28446763
TI  - Hanging Drop, A Best Three-Dimensional (3D) Culture Method for Primary Buffalo
      and Sheep Hepatocytes.
AB  - Livestock, having close resemblance to humans, could be a better source of
      primary hepatocytes than rodents. Herein, we successfully developed three
      dimensional (3D) culturing system for primary sheep and buffalo hepatocytes. The
      3D-structures of sheep hepatocytes were formed on the fifth-day and maintained
      until the tenth-day on polyHEMA-coated plates and in hanging drops with William's
      E media (HDW). Between the cultured and fresh cells, we observed a similar
      expression of GAPDH, HNF4alpha, ALB, CYP1A1, CK8 and CK18. Interestingly, a
      statistically significant increase was noted in the TAT, CPS, AFP, AAT, GSP and
      PCNA expression. In buffalo hepatocytes culture, 3D-like structures were formed
      on the third-day and maintained until the sixth-day on polyHEMA and HDW. The
      expression of HNF4alpha, GSP, CPS, AFP, AAT, PCNA and CK18 was similar between
      cultured and fresh cells. Further, a statistically significant increase in the
      TAT and CK8 expression, and a decrease in the GAPDH, CYP1A1 and ALB expression
      were noted. Among the culture systems, HDW maintained the liver transcript
      markers more or less similar to the fresh hepatocytes of the sheep and buffalo
      for ten and six days, respectively. Taken together, hanging drop is an efficient
      method for 3D culturing of primary sheep and buffalo hepatocytes.

PMID- 28446764
TI  - Complexity of genetic mechanisms conferring nonuniformity of recombination in
      maize.
AB  - Recombinations occur nonuniformly across the maize genome. To dissect the genetic
      mechanisms underlying the nonuniformity of recombination, we performed
      quantitative trait locus (QTL) mapping using recombinant inbred line populations.
      Genome-wide QTL scan identified hundreds of QTLs with both cis-prone and trans-
      effects for recombination number variation. To provide detailed insights into cis
      factors associated with recombination variation, we examined the genomic
      features around recombination hot regions, including density of genes, DNA
      transposons, retrotransposons, and some specific motifs. Compared to
      recombination variation in whole genome, more QTLs were mapped for variations in
      recombination hot regions. The majority QTLs for recombination hot regions are
      trans-QTLs and co-localized with genes from the recombination pathway. We also
      found that recombination variation was positively associated with the presence of
      genes and DNA transposons, but negatively related to the presence of long
      terminal repeat retrotransposons. Additionally, 41 recombination hot regions were
      fine-mapped. The high-resolution genotyping of five randomly selected regions in
      two F2 populations verified that they indeed have ultra-high recombination
      frequency, which is even higher than that of the well-known recombination hot
      regions sh1-bz and a1-sh2. Taken together, our results further our understanding
      of recombination variation in plants.

PMID- 28446765
TI  - Three-dimensional modeling of single stranded DNA hairpins for aptamer-based
      biosensors.
AB  - Aptamers consist of short oligonucleotides that bind specific targets. They
      provide advantages over antibodies, including robustness, low cost, and
      reusability. Their chemical structure allows the insertion of reporter molecules
      and surface-binding agents in specific locations, which have been recently
      exploited for the development of aptamer-based biosensors and direct detection
      strategies. Mainstream use of these devices, however, still requires significant
      improvements in optimization for consistency and reproducibility. DNA aptamers
      are more stable than their RNA counterparts for biomedical applications but have
      the disadvantage of lacking the wide array of computational tools for RNA
      structural prediction. Here, we present the first approach to predict from
      sequence the three-dimensional structures of single stranded (ss) DNA required
      for aptamer applications, focusing explicitly on ssDNA hairpins. The approach
      consists of a pipeline that integrates sequentially building ssDNA secondary
      structure from sequence, constructing equivalent 3D ssRNA models, transforming
      the 3D ssRNA models into ssDNA 3D structures, and refining the resulting ssDNA 3D
      structures. Through this pipeline, our approach faithfully predicts the
      representative structures available in the Nucleic Acid Database and Protein Data
      Bank databases. Our results, thus, open up a much-needed avenue for integrating
      DNA in the computational analysis and design of aptamer-based biosensors.

PMID- 28446766
TI  - Leukemia and Risk of Venous Thromboembolism: A Meta-analysis and Systematic
      Review of 144 Studies Comprising 162,126 Patients.
AB  - Venous thromboembolism (VTE) has significant clinical implications in leukemia
      patients. However, the actual frequency of this complication remains unknown. We
      performed a systematic review and meta-analysis to better estimate the frequency
      of this complication and to assess the risk factors that contribute to its
      occurrence. We searched several databases, including PubMed, Embase, and Web of
      Science, and assessed study quality using the Newcastle-Ottawa scale. The pooled
      frequency of VTE in leukemia patients was calculated. A total of 144 studies met
      the eligibility criteria. The incidence rate (IR) of VTE from 72 prospective
      studies comprising 9,061 patients was 5% (95%CI: 4-6%). The incidence rate (IR)
      of VTE in ALL, CLL, total-AML, and CML population was 5% (95%CI: 4-6%), 3%
      (95%CI: 2-5%), 6% (95%CI: 4-8%) and 13% (95%CI: 1-36%). The incidence of VTE was
      markedly decreased among ALL patients who received anticoagulation treatment (IR:
      1%, 95%CI: 0-6%) or concentrates therapy (IR: 3%, 95%CI: 0-9%). The overall
      incidence of VTE in the leukemia population was high, particularly in transplant
      recipients, who had the highest risk (IR: 8%, 95% CI: 4-13%). Prophylactic
      approaches could significantly decrease the occurrence of VTE events.

PMID- 28446768
TI  - Linear dynamics of classical spin as Mobius transformation.
AB  - Though the overwhelming majority of natural processes occur far from the
      equilibrium, general theoretical approaches to non-equilibrium phase transitions
      remain scarce. Recent breakthroughs introduced a description of open dissipative
      systems in terms of non-Hermitian quantum mechanics enabling the identification
      of a class of non-equilibrium phase transitions associated with the loss of
      combined parity (reflection) and time-reversal symmetries. Here we report that
      the time evolution of a single classical spin (e.g. monodomain ferromagnet)
      governed by the Landau-Lifshitz-Gilbert-Slonczewski equation in the absence of
      magnetic anisotropy terms is described by a Mobius transformation in complex
      stereographic coordinates. We identify the parity-time symmetry-breaking phase
      transition occurring in spin-transfer torque-driven linear spin systems as a
      transition between hyperbolic and loxodromic classes of Mobius transformations,
      with the critical point of the transition corresponding to the parabolic
      transformation. This establishes the understanding of non-equilibrium phase
      transitions as topological transitions in configuration space.

PMID- 28446767
TI  - Two-photon autofluorescence lifetime imaging of human skin papillary dermis in
      vivo: assessment of blood capillaries and structural proteins localization.
AB  - The papillary dermis of human skin is responsible for its biomechanical
      properties and for supply of epidermis with chemicals. Dermis is mainly composed
      of structural protein molecules, including collagen and elastin, and contains
      blood capillaries. Connective tissue diseases, as well as cardiovascular
      complications have manifestations on the molecular level in the papillary dermis
      (e.g. alteration of collagen I and III content) and in the capillary structure.
      In this paper we assessed the molecular structure of internal and external
      regions of skin capillaries using two-photon fluorescence lifetime imaging (FLIM)
      of endogenous compounds. It was shown that the capillaries are characterized by a
      fast fluorescence decay, which is originated from red blood cells and blood
      plasma. Using the second harmonic generation signal, FLIM segmentation was
      performed, which provided for spatial localization and fluorescence decay
      parameters distribution of collagen I and elastin in the dermal papillae. It was
      demonstrated that the lifetime distribution was different for the inner area of
      dermal papillae around the capillary loop that was suggested to be due to
      collagen III. Hence, we propose a generalized approach to two-photon imaging of
      the papillary dermis components, which extends the capabilities of this technique
      in skin diagnosis.

PMID- 28446769
TI  - Identification of key proteins and pathways in cadmium tolerance of Lactobacillus
      plantarum strains by proteomic analysis.
AB  - Our previous study confirmed the protective potential of Lactobacillus plantarum
      (L. plantarum) strains in alleviation of cadmium (Cd) toxicity in vivo and
      demonstrated that the observed protection largely depended on the tolerance of
      the strains to Cd-induced stress. It was also observed that there were
      significant intra-species differences in Cd tolerance of L. plantarum strains. In
      this study, we investigated the mechanism of Cd induced stress response of L.
      plantarum strains using the isobaric tags for relative and absolute quantitation
      (iTRAQ) based comparative proteomics. L. plantarum CCFM8610 (strongly resistant
      to Cd) and L. plantarum CCFM191 (sensitive to Cd) were selected as target
      strains, and their proteomic profiles in the presence and absence of Cd exposure
      were compared. We propose that the underlying mechanism of the exceptional Cd
      tolerance of CCFM8610 may be attributed to the following: (a) a specific energy
      conservation survival mode; (b) mild induction of its cellular defense and repair
      system;

PMID- 28446770
TI  - Instability of 8E5 calibration standard revealed by digital PCR risks inaccurate
      quantification of HIV DNA in clinical samples by qPCR.
AB  - ABTRACT: Establishing a cure for HIV is hindered by the persistence of latently
      infected cells which constitute the viral reservoir. Real-time qPCR, used for
      quantification of this reservoir by measuring HIV DNA, requires external
      calibration; a common choice of calibrator is the 8E5 cell line, which is assumed
      to be stable and to contain one HIV provirus per cell. In contrast, digital PCR
      requires no external calibration and potentially provides 'absolute'
      quantification. We compared the performance of qPCR and dPCR in quantifying HIV
      DNA in 18 patient samples. HIV DNA was detected in 18 by qPCR and in 15 by dPCR,
      the difference being due to the smaller sample volume analysed by dPCR. There was
      good quantitative correlation (R2 = 0.86) between the techniques but on average
      dPCR values were only 60% of qPCR values. Surprisingly, investigation revealed
      that this discrepancy was due to loss of HIV DNA from the 8E5 cell calibrant. 8E5
      extracts from two other sources were also shown to have significantly less than
      one HIV DNA copy per cell and progressive loss of HIV from 8E5 cells during
      culture was demonstrated. We therefore suggest that the copy number of HIV in 8E5
      extracts be established by dPCR prior to use as calibrator.

PMID- 28446771
TI  - Monitoring global protein thiol-oxidation and protein S-mycothiolation in
      Mycobacterium smegmatis under hypochlorite stress.
AB  - Mycothiol (MSH) is the major low molecular weight (LMW) thiol in Actinomycetes.
      Here, we used shotgun proteomics, OxICAT and RNA-seq transcriptomics to analyse
      protein S-mycothiolation, reversible thiol-oxidations and their impact on gene
      expression in Mycobacterium smegmatis under hypochlorite stress. In total, 58 S
      mycothiolated proteins were identified under NaOCl stress that are involved in
      energy metabolism, fatty acid and mycolic acid biosynthesis, protein translation,
      redox regulation and detoxification. Protein S-mycothiolation was accompanied by
      MSH depletion in the thiol-metabolome. Quantification of the redox state of 1098
      Cys residues using OxICAT revealed that 381 Cys residues (33.6%) showed >10%
      increased oxidations under NaOCl stress, which overlapped with 40 S-mycothiolated
      Cys-peptides. The absence of MSH resulted in a higher basal oxidation level of
      338 Cys residues (41.1%). The RseA and RshA anti-sigma factors and the Zur and
      NrdR repressors were identified as NaOCl-sensitive proteins and their oxidation
      resulted in an up-regulation of the SigH, SigE, Zur and NrdR regulons in the RNA
      seq transcriptome. In conclusion, we show here that NaOCl stress causes
      widespread thiol-oxidation including protein S-mycothiolation resulting in
      induction of antioxidant defense mechanisms in M. smegmatis. Our results further
      reveal that MSH is important to maintain the reduced state of protein thiols.

PMID- 28446772
TI  - Large-scale SNP screenings identify markers linked with GCRV resistant traits
      through transcriptomes of individuals and cell lines in Ctenopharyngodon idella.
AB  - Grass carp (Ctenopharyngodon idella) is an important economic species in
      freshwater aquaculture and its industry has been confined due to variety
      degeneration and frequent diseases. Marker-assisted selection is a feasible
      method for selective breeding of new varieties. Transcriptome data have greatly
      facilitated high-throughput single nucleotide polymorphism (SNP) marker discovery
      and phenotype association study. In this study, we gained a total of 25,981 and
      5,775 high quality SNPs in two transcriptomes from individuals and cell lines,
      respectively. Comparative transcriptome analysis identified 413 and 832 grass
      carp reovirus (GCRV)-resistant-association SNPs as well as 1,381 and 1,606 GCRV
      susceptible-association SNPs in individuals and cell lines, respectively.
      Integrated analysis indicated 22 genes with single SNP share common
      resistant/susceptible traits in two transcriptomes. Furthermore, we infected
      grass carp with GCRV, genotyping and association analyses were performed, and 9
      in 22 SNPs were confirmed by PCR-RFLP. Meanwhile, mRNA expression profiles of 6
      genes containing confirmed SNPs were examined by qRT-PCR. The results
      demonstrated that mRNA expressions were significant differences in
      resistant/susceptible individuals and cell lines. The present study develops an
      important strategy for high throughput screening of phenotype association genetic
      markers and the results will serve in grass carp breeding for GCRV resistance.

PMID- 28446773
TI  - Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced
      status epilepticus in mice.
AB  - Inflammatory processes in brain tissue have been described in human epilepsy of
      various etiologies and in experimental models of seizures. High mobility group
      box-1 (HMGB1) is now recognized as representative of damage-associated molecular
      patterns (DAMPs). In the present study, we focused on whether anti-HMGB1 antibody
      treatment could relieve status epilepticus- triggered BBB breakdown and
      inflammation response in addition to the seizure behavior itself. Pilocarpine and
      methyl-scopolamine were used to establish the acute seizure model. Anti-HMGB1 mAb
      showed inhibitory effects on leakage of the BBB, and on the HMGB1 translocation
      induced by pilocarpine. The expression of inflammation-related factors, such as
      MCP-1, CXCL-1, TLR-4, and IL-6 in hippocampus and cerebral cortex were down
      regulated by anti-HMGB1 mAb associated with the number of activated astrocytes,
      microglial cells as well as the expression of IL-1beta. Both hematoxylin & eosin
      and TUNEL staining showed that the apoptotic cells could be reduced after anti
      HMGB1 mAb treatment. The onset and latency of Racine stage five were
      significantly prolonged in the anti-HMGB1 mAb group. These results suggested that
      anti-HMGB1 mAb prevented the BBB permeability, reduced HMGB1 translocation while
      inhibiting the expression of inflammation-related factors, protected against
      neural cell apoptosis and prolonged Racine stage 5 seizure onset and latency.

PMID- 28446774
TI  - Liver ERalpha regulates AgRP neuronal activity in the arcuate nucleus of female
      mice.
AB  - Recent work revealed the major role played by liver Estrogen Receptor alpha
      (ERalpha) in the regulation of metabolic and reproductive functions. By using
      mutant mice with liver-specific ablation of Eralpha, we here demonstrate that the
      hepatic ERalpha is essential for the modulation of the activity of Agouti Related
      Protein (AgRP) neurons in relation to the reproductive cycle and diet. Our
      results suggest that the alterations of hepatic lipid metabolism due to the lack
      of liver ERalpha activity are responsible for a neuroinflammatory status that
      induces refractoriness of AgRP neurons to reproductive and dietary stimuli. The
      study therefore points to the liver ERalpha as a necessary sensor for the
      coordination of systemic energy metabolism and reproductive functions.

PMID- 28446775
TI  - Delivering Prolonged Intensive Care to a Non-human Primate: A High Fidelity
      Animal Model of Critical Illness.
AB  - Critical care needs have been rising in recent decades as populations age and
      comorbidities increase. Sepsis-related admissions to critical care contribute up
      to 50% of volume and septic shock carries a 35-54% fatality rate. Improvements in
      sepsis-related care and mortality would have a significant impact of a resource
      intensive area of health care delivery. Unfortunately, research has been hampered
      by the lack of an animal model that replicates the complex care provided to
      humans in an intensive care unit (ICU). We developed a protocol to provide full
      ICU type supportive care to Rhesus macaques. This included mechanical
      ventilation, continuous sedation, fluid and electrolyte management and
      vasopressor support in response to Ebolavirus-induced septic shock. The animals
      accurately recapitulated human responses to a full range of ICU interventions
      (e.g. fluid resuscitation). This model can overcome current animal model
      limitations by accurately emulating the complexity of ICU care and thereby
      provide a platform for testing new interventions in critical care and sepsis
      without placing patients at risk.

PMID- 28446776
TI  - The use of electronic alerts in primary care computer systems to identify the
      over-prescription of short-acting beta2-agonists in people with asthma: a
      protocol for a systematic review.

PMID- 28446777
TI  - Structural investigations on orotate phosphoribosyltransferase from Mycobacterium
      tuberculosis, a key enzyme of the de novo pyrimidine biosynthesis.
AB  - The Mycobacterium tuberculosis orotate phosphoribosyltransferase (MtOPRT)
      catalyses the conversion of alpha-D-5-phosphoribosyl-1-pyrophosphate (PRPP) and
      orotate (OA) in pyrophosphate and orotidine 5'-monophosphate (OMP), in presence
      of Mg2+. This enzyme is the only responsible for the synthesis of orotidine 5'
      monophosphate, a key precursor in the de novo pyrimidine biosynthesis pathway,
      making MtOPRT an attractive drug target for the development of antitubercular
      agents. We report the crystal structures of MtOPRT in complex with PRPP (2.25 A
      resolution), inorganic phosphate (1.90 A resolution) and the exogenous compound
      Fe(III) dicitrate (2.40 A resolution). The overall structure of the mycobacterial
      enzyme is highly similar to those described for other OPRTases, with the
      "flexible loop" assuming a well define conformation and making specific contacts
      with the Fe(III)-dicitrate complex. The structures here reported add to the
      knowledge of a potential drug target for tuberculosis, and will provide a useful
      tool for the structure-based drug design of potent enzyme inhibitors.

PMID- 28446778
TI  - Tumor necrosis factor prevents Candida albicans biofilm formation.
AB  - Candida species are commensals but some develop biofilms in prosthetic materials
      and host surfaces that may represent up to 30% of deaths related to infections,
      particularly in immunosuppressed patients. Tumor necrosis factor (TNF) exhibits a
      plethora of functions in host defense mechanisms whereas excessive release of TNF
      in inflammation promotes tissue damage. Cytokines released in an inflammatory
      milieu may influence the development of microorganisms either by promoting their
      growth or displaying antimicrobial activity. In protozoa, TNF may affect growth
      by coupling through a lectin-like domain, distinct from TNF receptors. TNF was
      also shown to interact with bacteria via a mechanism that does not involve
      classical TNF receptors. Using an in vitro C. albicans biofilm model, we show
      that TNF dose-dependently prevents biofilm development that is blocked by
      incubating TNF with N,N'-diacetylchitobiose, a major carbohydrate component of C.
      albicans cell wall. This finding represents a relevant and hitherto unknown
      mechanism that adds to the understanding of why TNF blockade is associated with
      opportunistic C. albicans infections.

PMID- 28446780
TI  - Holocene winter climate variability in Central and Eastern Europe.
AB  - Among abundant reconstructions of Holocene climate in Europe, only a handful has
      addressed winter conditions, and most of these are restricted in length and/or
      resolution. Here we present a record of late autumn through early winter air
      temperature and moisture source changes in East-Central Europe for the Holocene,
      based on stable isotopic analysis of an ice core recovered from a cave in the
      Romanian Carpathian Mountains. During the past 10,000 years, reconstructed
      temperature changes followed insolation, with a minimum in the early Holocene,
      followed by gradual and continuous increase towards the mid-to-late-Holocene peak
      (between 4-2 kcal BP), and finally by a decrease after 0.8 kcal BP towards a
      minimum during the Little Ice Age (AD 1300-1850). Reconstructed early Holocene
      atmospheric circulation patterns were similar to those characteristics of the
      negative phase of the North Atlantic Oscillation (NAO), while in the late
      Holocene they resembled those prevailing in the positive NAO phase. The
      transition between the two regimes occurred abruptly at around 4.7 kcal BP.
      Remarkably, the widespread cooling at 8.2 kcal BP is not seen very well as a
      temperature change, but as a shift in moisture source, suggesting weaker
      westerlies and increased Mediterranean cyclones penetrating northward at this
      time.

PMID- 28446781
TI  - Inkjet Printing of High Performance Transistors with Micron Order Chemically Set
      Gaps.
AB  - This paper reports a 100% inkjet printed transistor with a short channel of
      approximately 1 um with an operating speed up to 18.21 GHz. Printed electronics
      are a burgeoning area in electronics development, but are often stymied by the
      large minimum feature size. To combat this, techniques were developed to allow
      for the printings of much shorter transistor channels. The small gap size is
      achieved through the use of silver inks with different chemical properties to
      prevent mixing. The combination of the short channel and semiconducting carbon
      nanotubes (CNT) allows for an exceptional experimentally measured on/off ratio of
      106. This all inkjet printed transistor allows for the fabrication of devices
      using roll-to-roll methodologies with no additional overhead compared to current
      state of the art production methods.

PMID- 28446779
TI  - Functional Neuronal Differentiation of Injury-Induced Muscle-Derived Stem Cell
      Like Cells with Therapeutic Implications.
AB  - Mammalian skeletal muscles contain a number of heterogeneous cell populations.
      Our previous study characterized a unique population of myogenic lineage stem
      cells that can be isolated from adult mammalian skeletal muscles upon injury.
      These injury-induced muscle-derived stem cell-like cells (iMuSCs) displayed a
      multipotent state with sensitiveness and strong migration abilities. Here, we
      report that these iMuSCs have the capability to form neurospheres that represent
      multiple neural phenotypes. The induced neuronal cells expressed various neuron
      specific proteins, their mRNA expression during neuronal differentiation
      recapitulated embryonic neurogenesis, they generated action potentials, and they
      formed functional synapses in vitro. Furthermore, the transplantation of iMuSCs
      or their cell extracts into the muscles of mdx mice (i.e., a mouse model of
      Duchenne Muscular Dystrophy [DMD]) could restore the morphology of their
      previously damaged neuromuscular junctions (NMJs), suggesting that the beneficial
      effects of iMuSCs may not be restricted to cell restoration alone, but also due
      to their transient paracrine actions. The current study reveals the essential
      role of iMuSCs in the restoration of NMJs related to injuries and diseases.

PMID- 28446782
TI  - High-Performance Flexible Supercapacitors obtained via Recycled Jute: Bio-Waste
      to Energy Storage Approach.
AB  - In search of affordable, flexible, lightweight, efficient and stable
      supercapacitors, metal oxides have been shown to provide high charge storage
      capacity but with poor cyclic stability due to structural damage occurring during
      the redox process. Here, we develop an efficient flexible supercapacitor obtained
      by carbonizing abundantly available and recyclable jute. The active material was
      synthesized from jute by a facile hydrothermal method and its electrochemical
      performance was further enhanced by chemical activation. Specific capacitance of
      408 F/g at 1 mV/s using CV and 185 F/g at 500 mA/g using charge-discharge
      measurements with excellent flexibility (~100% retention in charge storage
      capacity on bending) were observed. The cyclic stability test confirmed no loss
      in the charge storage capacity of the electrode even after 5,000 charge-discharge
      measurements. In addition, a supercapacitor device fabricated using this
      carbonized jute showed promising specific capacitance of about 51 F/g, and
      improvement of over 60% in the charge storage capacity on increasing temperature
      from 5 to 75  degrees C. Based on these results, we propose that recycled jute
      should be considered for fabrication of high-performance flexible energy storage
      devices at extremely low cost.

PMID- 28446783
TI  - A common neonicotinoid pesticide, thiamethoxam, impairs honey bee flight ability.
AB  - Pesticides can pose environmental risks, and a common neonicotinoid pesticide,
      thiamethoxam, decreases homing success in honey bees. Neonicotinoids can alter
      bee navigation, but we present the first evidence that neonicotinoid exposure
      alone can impair the physical ability of bees to fly. We tested the effects of
      acute or chronic exposure to thiamethoxam on the flight ability of foragers in
      flight mills. Within 1 h of consuming a single sublethal dose (1.34 ng/bee),
      foragers showed excitation and significantly increased flight duration (+78%) and
      distance (+72%). Chronic exposure significantly decreased flight duration (-54%),
      distance (-56%), and average velocity (-7%) after either one or two days of
      continuous exposure that resulted in bees ingesting field-relevant thiamethoxam
      doses of 1.96-2.90 ng/bee/day. These results provide the first demonstration that
      acute or chronic exposure to a neonicotinoid alone can significantly alter bee
      flight. Such exposure may impair foraging and homing, which are vital to normal
      colony function and ecosystem services.

PMID- 28446785
TI  - Possible role of pandemic AH1N1 swine flu virus in a childhood leukemia cluster.

PMID- 28446784
TI  - A reconfigurable all-optical ultrasound transducer array for 3D endoscopic
      imaging.
AB  - A miniature all-optical ultrasound imaging system is presented that generates
      three-dimensional images using a stationary, real acoustic source aperture.
      Discrete acoustic sources were sequentially addressed by scanning a focussed
      optical beam across the proximal end of a coherent fibre bundle; high-frequency
      ultrasound (156% fractional bandwidth centred around 13.5 MHz) was generated
      photoacoustically in the corresponding regions of an optically absorbing coating
      deposited at the distal end. Paired with a single fibre-optic ultrasound
      detector, the imaging probe (3.5 mm outer diameter) achieved high on-axis
      resolutions of 97 MUm, 179 MUm and 110 MUm in the x, y and z directions,
      respectively. Furthermore, the optical scan pattern, and thus the acoustic source
      array geometry, was readily reconfigured. Implementing four different array
      geometries revealed a strong dependency of the image quality on the source
      location pattern. Thus, by employing optical technology, a miniature ultrasound
      probe was fabricated that allows for arbitrary source array geometries, which is
      suitable for three-dimensional endoscopic and laparoscopic imaging, as was
      demonstrated on ex vivo porcine cardiac tissue.

PMID- 28446787
TI  - Neural development: Keeping a lid on alternative fates.

PMID- 28446788
TI  - Resolution-enhanced Fourier ptychographic microscopy based on high-numerical
      aperture illuminations.
AB  - High-resolution and wide field-of-view (FOV) microscopic imaging plays a central
      role in diverse applications such as high-throughput screening and digital
      pathology. However, conventional microscopes face inherent trade-offs between the
      spatial resolution and FOV, which are fundamental limited by the space-bandwidth
      product (SBP) of the optical system. The resolution-FOV tradeoff can be
      effectively decoupled in Fourier ptychography microscopy (FPM), however, to date,
      the effective imaging NA achievable with a typical FPM system is still limited to
      the range of 0.4-0.7. Herein, we report, for the first time, a high-NA
      illumination based resolution-enhanced FPM (REFPM) platform, in which a LED-array
      based digital oil-immersion condenser is used to create high-angle programmable
      plane-wave illuminations, endowing a 10*, 0.4 NA objective lens with final
      effective imaging performance of 1.6 NA. With REFPM, we present the highest
      resolution results with a unprecedented half-pitch resolution of 154 nm at a
      wavelength of 435 nm across a wide FOV of 2.34 mm2, corresponding to an SBP of
      98.5 megapixels (~50 times higher than that of the conventional incoherent
      microscope with the same resolution). Our work provides an important step of FPM
      towards high-resolution large-NA imaging applications, generating comparable
      resolution performance but significantly broadening the FOV of conventional oil
      immersion microscopes.

PMID- 28446789
TI  - Imaging of underground cavities with cosmic-ray muons from observations at Mt.
      Echia (Naples).
AB  - Muography is an imaging technique based on the measurement of absorption profiles
      for muons as they pass through rocks and earth. Muons are produced in the
      interactions of high-energy cosmic rays in the Earth's atmosphere. The technique
      is conceptually similar to usual X-ray radiography, but with extended
      capabilities of investigating over much larger thicknesses of matter thanks to
      the penetrating power of high-energy muons. Over the centuries a complex system
      of cavities has been excavated in the yellow tuff of Mt. Echia, the site of the
      earliest settlement of the city of Naples in the 8th century BC. A new generation
      muon detector designed by us, was installed under a total rock overburden of
      about 40 metres. A 26 days pilot run provided about 14 millions of muon events. A
      comparison of the measured and expected muon fluxes improved the knowledge of the
      average rock density. The observation of known cavities proved the validity of
      the muographic technique. Hints on the existence of a so far unknown cavity was
      obtained. The success of the investigation reported here demonstrates the
      substantial progress of muography in underground imaging and is likely to open
      new avenues for its widespread utilisation.

PMID- 28446786
TI  - How and why do T cells and their derived cytokines affect the injured and healthy
      brain?
AB  - The evolution of adaptive immunity provides enhanced defence against specific
      pathogens, as well as homeostatic immune surveillance of all tissues. Despite
      being 'immune privileged', the CNS uses the assistance of the immune system in
      physiological and pathological states. In this Opinion article, we discuss the
      influence of adaptive immunity on recovery after CNS injury and on cognitive and
      social brain function. We further extend a hypothesis that the pro-social effects
      of interferon-regulated genes were initially exploited by pathogens to increase
      host-host transmission, and that these genes were later recycled by the host to
      form part of an immune defence programme. In this way, the evolution of adaptive
      immunity may reflect a host-pathogen 'arms race'.

PMID- 28446790
TI  - VAV1 regulates experimental autoimmune arthritis and is associated with anti-CCP
      negative rheumatoid arthritis.

PMID- 28446791
TI  - Tissue Distribution of the MERS-Coronavirus Receptor in Bats.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) has been shown to infect
      both humans and dromedary camels using dipeptidyl peptidase-4 (DPP4) as its
      receptor. The distribution of DPP4 in the respiratory tract tissues of humans and
      camels reflects MERS-CoV tropism. Apart from dromedary camels, insectivorous bats
      are suggested as another natural reservoir for MERS-like-CoVs. In order to gain
      insight on the tropism of these viruses in bats, we studied the DPP4 distribution
      in the respiratory and extra-respiratory tissues of two frugivorous bat species
      (Epomophorus gambianus and Rousettus aegyptiacus) and two insectivorous bat
      species (Pipistrellus pipistrellus and Eptesicus serotinus). In the frugivorous
      bats, DPP4 was present in epithelial cells of both the respiratory and the
      intestinal tract, similar to what has been reported for camels and humans. In the
      insectivorous bats, however, DPP4 expression in epithelial cells of the
      respiratory tract was almost absent. The preferential expression of DPP4 in the
      intestinal tract of insectivorous bats, suggests that transmission of MERS-like
      CoVs mainly occurs via the fecal-oral route. Our results highlight differences in
      the distribution of DPP4 expression among MERS-CoV susceptible species, which
      might influence variability in virus tropism, pathogenesis and transmission
      route.

PMID- 28446792
TI  - Sulfated Hyaluronan Derivatives Modulate TGF-beta1:Receptor Complex Formation:
      Possible Consequences for TGF-beta1 Signaling.
AB  - Glycosaminoglycans are known to bind biological mediators thereby modulating
      their biological activity. Sulfated hyaluronans (sHA) were reported to strongly
      interact with transforming growth factor (TGF)-beta1 leading to impaired
      bioactivity in fibroblasts. The underlying mechanism is not fully elucidated yet.
      Examining the interaction of all components of the TGF-beta1:receptor complex
      with sHA by surface plasmon resonance, we could show that highly sulfated HA
      (sHA3) blocks binding of TGF-beta1 to its TGF-beta receptor-I (TbetaR-I) and -II
      (TbetaR-II). However, sequential addition of sHA3 to the TbetaR-II/TGF-beta1
      complex led to a significantly stronger recruitment of TbetaR-I compared to a
      complex lacking sHA3, indicating that the order of binding events is very
      important. Molecular modeling suggested a possible molecular mechanism in which
      sHA3 could potentially favor the association of TbetaR-I when added sequentially.
      For the first time bioactivity of TGF-beta1 in conjunction with sHA was
      investigated at the receptor level. TbetaR-I and, furthermore, Smad2
      phosphorylation were decreased in the presence of sHA3 indicating the formation
      of an inactive signaling complex. The results contribute to an improved
      understanding of the interference of sHA3 with TGF-beta1:receptor complex
      formation and will help to further improve the design of functional biomaterials
      that interfere with TGF-beta1-driven skin fibrosis.

PMID- 28446793
TI  - Demonstration of Shot-noise-limited Swept Source OCT Without Balanced Detection.
AB  - Optical coherence tomography (OCT) has been utilized in a rapidly growing number
      of clinical and scientific applications. In particular, swept source OCT (SS-OCT)
      has attracted many attentions due to its excellent performance. So far however,
      the limitations of existing photon detectors have prevented achieving shot-noise
      limited sensitivity without using balanced-detection scheme in SS-OCT, even when
      superconducting single-photon detectors were used. Unfortunately, balanced
      detection increases OCT system size and cost, as it requires many additional
      components to boost the laser power and maintain near ideal balanced performance
      across the whole optical bandwidth. Here we show for the first time that a photon
      detector is capable of achieving shot noise limited performance without using the
      balanced-detection technique in SS-OCT. We built a system using a so-called
      electron-injection photodetector, with a cutoff-wavelength of 1700 nm. Our system
      achieves a shot-noise-limited sensitivity of about -105 dB at a reference laser
      power of ~350 nW, which is more than 30 times lower laser power compared with the
      best-reported results. The high sensitivity of the electron-injection detector
      allows utilization of micron-scale tunable laser sources (e.g. VCSEL) and
      eliminates the need for fiber amplifiers and highly precise couplers, which are
      an essential part of the conventional SS-OCT systems.

PMID- 28446794
TI  - Up Scalable Full Colour Plasmonic Pixels with Controllable Hue, Brightness and
      Saturation.
AB  - It has long been the interests of scientists to develop ink free colour printing
      technique using nano structured materials inspired by brilliant colours found in
      many creatures like butterflies and peacocks. Recently isolated metal nano
      structures exhibiting preferential light absorption and scattering have been
      explored as a promising candidate for this emerging field. Applying such
      structures in practical use, however, demands the production of individual
      colours with distinct reflective peaks, tunable across the visible wavelength
      region combined with controllable colour attributes and economically feasible
      fabrication. Herein, we present a simple yet efficient colour printing approach
      employing sub-micrometer scale plasmonic pixels of single constituent metal
      structure which supports near unity broadband light absorption at two distinct
      wavelengths, facilitating the creation of saturated colours. The dependence of
      these resonances on two different parameters of the same pixel enables
      controllable colour attributes such as hue, brightness and saturation across the
      visible spectrum. The linear dependence of colour attributes on the pixel
      parameters eases the automation; which combined with the use of inexpensive and
      stable aluminum as functional material will make this colour design strategy
      relevant for use in various commercial applications like printing micro images
      for security purposes, consumer product colouration and functionalized decoration
      to name a few.

PMID- 28446795
TI  - Variants in the IL7RA gene confer susceptibility to multiple sclerosis in
      Caucasians: evidence based on 9734 cases and 10436 controls.
AB  - Recently, numerous genome wide association studies (GWAS) and other case-control
      association studies examining the relationship between interleukin-7 receptor
      alpha chain (IL7RA) gene rs3194051, rs987107, rs11567686, and rs11567685 variants
      and multiple sclerosis (MS) risk have been conducted, but the conclusions have
      been inconsistent. The main objective of this meta-analysis was to more precisely
      explore the association of these four IL7RA variants with MS development. Twenty
      seven eligible studies involving 9734 cases and 10436 controls were included in
      the present meta-analysis. Power calculation, publication bias, sensitivity
      analysis and cumulative meta-analysis were performed to derive a reliable
      conclusion. Our study indicated three IL7RA loci were significantly associated
      with increasing MS risk (rs3194051: recessive model: OR = 1.22, 95% CI 1.08-1.38;
      rs987107: recessive model: OR = 1.44, 95% CI 1.22-1.69; and rs11567686: dominant
      model: OR = 1.18, 95% CI 1.01-1.37). Additionally, IL7RA rs11567685 variants
      might not be related to MS development. In all, IL7RA locus polymorphisms could
      play an important role in the predisposition to MS, which could contribute to a
      better understanding the pathogenesis of multiple sclerosis.

PMID- 28446796
TI  - The reinvention of twentieth century microscopy for three-dimensional imaging.
AB  - In just over a decade, the field of biomedical research has witnessed a radical
      evolution in technologies for the 3- and 4-dimensional imaging of biological
      samples. Light sheet fluorescence microscopy is quickly developing into a
      powerful approach for fast, volumetric imaging of cells, tissues and living
      organisms. This review touches on the development of 3-dimensional imaging, from
      its foundations, namely from the invention of confocal microscopy in the
      twentieth century to more recent examples, notably the IsoView SPIM, the Lattice
      Light Sheet Microscope and swept confocally aligned planar excitation. These
      technologies overcome the limitations of conventional optical sectioning
      techniques and enable unprecedented levels of spatio-temporal resolution with low
      levels of phototoxicity. Developing in parallel with powerful computational
      approaches, light sheet based methods promise to completely transform cell
      biology as we know it today.

PMID- 28446797
TI  - Fetiform teratoma was a parthenogenetic tumor arising from a mature ovum.
AB  - The aim of this study was to investigate the parthenogenetic origin of fetiform
      teratoma by using molecular genetic studies and methylation status analyses. A
      fetiform teratoma was removed from a 35-year-old nulligravida woman. Genotyping
      of microsatellite marker loci, microarray analysis of single-nucleotide
      polymorphism (SNP) loci and methylation status analysis of the differentially
      methylated region (DMR) within the human IGF2-H19 locus were performed.
      Karyotypes of the host and the fetiform teratoma were 46, XX. The fetiform
      teratoma was homozygous at all loci and meiotic recombinations in the tumor were
      confirmed by SNP microarray analysis. Methylation analysis indicated that the
      host had both methylated and unmethylated IGF2-H19 DMR alleles, while the
      fetiform teratoma had unmethylated alleles only. Genetically, the fetiform
      teratoma had homozygous genotypes with meiotic recombination and a duplicated
      unmethylated host allele, indicating that it was a parthenogenetic tumor arising
      from a mature ovum after meiosis II. This is the first demonstration of a
      fetiform teratoma originating from a mature haploid ovum.

PMID- 28446799
TI  - Expanding the spectrum of skeletal dysplasia with immunodeficiency: a commentary
      on identification of biallelic EXTL3 mutations in a novel type of spondylo-epi
      metaphyseal dysplasia.

PMID- 28446798
TI  - Novel missense mutation in DLL4 in a Japanese sporadic case of Adams-Oliver
      syndrome.
AB  - Adams-Oliver syndrome (AOS, OMIM; 100300) is a rare genetic disease characterized
      by aplasia cutis congenita, terminal transverse limb defects and cutis marmorata
      with vascular anomalies such as congenital heart defects. The etiology of this
      syndrome has remained largely unknown but defective Notch signaling during
      vascular formation has been suggested. Here we describe a sporadic Japanese
      newborn case with clinically diagnosed AOS. Trio whole-exome sequencing
      identified a de novo, novel, heterozygous missense mutation in the Delta-like 4
      ligand gene (DLL4 c.572G>A, p.Arg191His) in the patient. DLL4 functions as a
      requisite ligand for NOTCH1 receptor, which is essential for vascular formation.
      Amino acid substitution of Arg191 to His was predicted by molecular models to
      interfere with direct binding between DLL4 and NOTCH1. DLL4 has recently been
      identified as a causative gene of an autosomal dominant type of AOS with milder
      symptoms. The case described here showed gradual recovery from skull defects
      after birth and no psychomotor developmental delay has been observed. This is the
      second report of an AOS case with DLL4 mutation, and the phenotypic
      characteristics between the two cases are compared and discussed.

PMID- 28446800
TI  - Oxidative stress evoked damages on rat sperm and attenuated antioxidant status on
      consumption of aspartame.
AB  - Although several studies on toxic effect of aspartame metabolite have been
      studied, controversial reports over the use of aspartame owing to the fact that
      it releases methanol as one of its metabolite during metabolism exist. This
      present study is proposed to investigate whether aspartame (40 mg kg-1 b.wt)
      administration for 90 days could induce oxidative stress and alter antioxidant
      status of epididymal sperm in Wistar strain male albino rats. To mimic the human
      methanol metabolism, methotrexate (MTX)-treated rats were included to study the
      effects of aspartame. Oral intubations of FDA approved 40 mg kg-1 b.wt aspartame
      were given daily for 90 days to Wistar strain male albino rats and studied along
      with controls and MTX-treated controls. Sperm count, viability, morphology,
      morphometry and motility were assessed. A significant decrease in sperm function
      of aspartame treated animals was observed when compared with the control and MTX
      control. The free radical generation were observed in epididymal sperm by
      assessing the scavenging enzymes, enzymatic and non-enzymatic antioxidants.
      Result suggest that there was a significant increase glutathione-s-transferase
      (GST), with a significant decrease in reduced glutathione (GSH), superoxide
      dismutase activity (SOD), glutathione peroxidase levels (GPx), catalase activity
      (CAT) and glutathione reductase concentration. The increase in free radicals
      generation could have ultimately caused the lipid peroxidation mediated damages
      on the testis. Aspartame treated animals also revealed the reduced space in
      seminiferous tubules, which resulted in reduced Leydig cells when compared with
      control in histopathology. These findings demonstrate that aspartame metabolites
      could be a contributing factor for development of oxidative stress in the
      epididymal sperm.

PMID- 28446802
TI  - Reply to 'Use of serum fibroblast growth factor 23 vs. plasma B-type natriuretic
      peptide levels in assessing the pathophysiology of patients with heart failure'.

PMID- 28446803
TI  - Observational study and participant-level meta-analysis on antihypertensive drug
      treatment-related cardiovascular risk.
AB  - Although antihypertensive therapy reduces cardiovascular risk, individuals who
      are treated with antihypertensive medication generally have a worse prognosis for
      cardiovascular disease than untreated people. We recently evaluated the impact of
      conventional blood pressure level based on two Japanese individual participant
      databases and found that conventional blood pressure at baseline was not or was
      weakly associated with cardiovascular events among patients under
      antihypertensive drug medication. In the general population in Ohasama and the
      Hypertension Objective Treatment Based on Measurement by Electrical Devices of
      Blood Pressures study, self-measured home blood pressure significantly predicted
      cardiovascular outcomes in patients under antihypertensive treatment.
      Hypertension is a chronic disease, and blood pressure must be evaluated with
      repeated measurements over a long period of time. Therefore, although not proven
      by a randomized controlled trial, it is likely that the long-term management of
      hypertension by antihypertensive drug treatment should be based on self-measured
      home blood pressure. We should also pay careful attention to the residual
      cardiovascular risk in treated patients.

PMID- 28446801
TI  - Genetic susceptibility to salt-sensitive hypertension in a Han Chinese
      population: a validation study of candidate genes.
AB  - Salt-sensitive hypertension is a complex disease associated with genetic factors.
      This study aimed to identify the association between 29 candidate single
      nucleotide polymorphisms and salt-sensitive hypertension in a Han Chinese
      population. Sixty-three participants with salt-sensitive hypertension and 279
      controls with salt-resistant hypertension were recruited. A modified Sullivan's
      acute oral saline load and diuresis shrinkage test was used to detect blood
      pressure salt sensitivity. Lifestyle risk factors were obtained via a
      questionnaire. We used the Sequenom Mass ARRAY Platform to genotype the 29
      candidate single-nucleotide polymorphisms, and the cumulative genetic risk score
      was used to evaluate the joint genetic effect. The frequencies of eight genotypes
      and five alleles in CYP11B2, PRKG1, ADRB2, FGF5, SLC8A1 and BCAT1 genes differed
      significantly between the salt-sensitive and salt-resistant hypertension groups.
      Multiple logistic regression adjusted for age and sex showed that subjects
      carrying rs7897633-A (PRKG1), rs434082-A (SLC8A1) and rs1042714-G (ADRB2) risk
      alleles had 1.83-, 2.84- and 2.40-fold increased risk for salt-sensitive
      hypertension, respectively. Combined risk allele analysis using the cumulative
      genetic risk score showed that subjects carrying one risk had 2.30-fold increased
      risk, and those carrying 2-4 risks had 3.32-fold increased risk for salt
      sensitive hypertension. Among 29 candidate single-nucleotide polymorphisms,
      rs7897633-A in PRKG1, rs434082-A in SLC8A1 and rs1042714-G in ADRB2 were
      significantly associated with salt-sensitive hypertension. A joint effect of
      single-nucleotide polymorphisms from different pathways contributed to a high
      risk of salt-sensitive hypertension.

PMID- 28446804
TI  - The effects of increasing calcium channel blocker dose vs. adding a diuretic to
      treatment regimens for patients with uncontrolled hypertension.
AB  - In patients with insufficient blood pressure (BP) control, despite using a
      combination regimen containing an angiotensin receptor blocker and a calcium
      channel blocker (CCB), whether a greater dose of CCB or adding a diuretic is more
      effective at lowering BP remains unclear. We conducted a multicenter randomized
      clinical trial to compare the efficacy of switching from the daily administration
      of a single-pill fixed-dose combination of irbesartan (100 mg) and amlodipine (5
      mg) to irbesartan (100 mg) with an increased dose of amlodipine (10 mg) (HD
      group, n=62) or irbesartan (100 mg) and amlodipine (5 mg) with 1 mg of indapamide
      (D group, n=63) in patients with poorly controlled hypertension. BP measured at
      home was monitored by a physician using a telemonitoring system. Between the HD
      and D groups, no significant differences were observed in morning home BP changes
      (mean reduction of systolic/diastolic BP, 1.7/0.9 mmHg; 95% confidence intervals,
      -2.4 to 5.7/-1.4 to 3.2; P=0.19/0.37), achievement rate of target BP (45.2% vs.
      42.9%, P=0.80), BP variability independent of the mean (P?0.74), other
      variability indices (P?0.55) and time to stabilization, which was calculated
      using a fitted analysis (13.1 days vs. 11.4 days, P=0.99). Although a significant
      increase in serum uric acid was observed in the D group (P<0.0001), neither
      clinically relevant abnormal laboratory test results nor critical BP changes were
      observed throughout the trial period. Both antihypertensive drug combination
      strategies were effective treatment options. Further investigation is required to
      determine the appropriate use of both therapies based on the various pathologies
      associated with hypertension.

PMID- 28446805
TI  - Biomarkers for right-sided heart failure.

PMID- 28446806
TI  - Response to Yatabe et al.

PMID- 28446807
TI  - Increased blood pressure in nesfatin/nuclebindin-2-transgenic mice.
AB  - Nesfatin/nucleobindin-2 (nesf/NUCB2), a precursor of the anorexigenic protein
      nesfatin-1, is selectively expressed in the hypothalamic nuclei, which are
      central to the regulation of the autonomic nervous system. The present study
      sought to investigate the involvement of nesf/NUCB2 in the regulation of blood
      pressure and ingestive behavior, by using nesf/NUCB2-transgenic (Tg) mice. Blood
      pressure and heart rates were measured under conscious and unconscious
      conditions. Twenty-four-hour water intake and urine volume of male nesf/NUCB2-Tg
      mice and their littermates in metabolic cages were measured. After killing,
      kidney weight was measured and the mRNA expression of epithelial sodium channel
      (ENaC)-alpha and ENaC-gamma was measured in the hypothalamus and kidney with real
      time PCR. Systolic, diastolic and mean blood pressure were significantly higher
      in nesf/NUCB2-Tg mice, but pulse rate was not affected in conscious mice. In
      contrast, isoflurane anesthesia prevented an increase in blood pressure in the
      nesf/NUCB2-Tg mice. Twenty-four-hour water intake and urine volume were
      significantly higher in the nesf/NUCB2-Tg mice than in their non-Tg littermates.
      Urine sodium concentration was significantly lower in the nesf/NUCB2-Tg mice,
      although the serum sodium concentration and urine sodium excretion were not
      different between the genotypes. Kidney weight was significantly higher in the
      nesf/NUCB2-Tg mice than their non-Tg littermates, although there were no clear
      differences in the kidney histological findings between genotypes. The mRNA
      expression of ENaC-gamma, but not ENaC-alpha, was decreased in the hypothalami of
      nesf/NUCB2-Tg mice. Our data suggested that Nesf/NUCB2 is involved in the
      regulation of blood pressure in the brain.

PMID- 28446808
TI  - Possible combinatorial effects of current smoking and alcohol intake on chronic
      kidney disease in a Japanese nationwide cross-sectional survey.

PMID- 28446809
TI  - Blood pressure management in patients with type 2 diabetes mellitus.
AB  - Hypertension aggravates macrovascular and microvascular diseases and mortality in
      patients with type 2 diabetes mellitus (T2DM). The current Japanese Society of
      Hypertension Guidelines of the Management of Hypertension (JSH 2014) recommends
      that antihypertensive medication should be initiated concomitantly with lifestyle
      modification when blood pressure (BP) is ?130/80 mm Hg and that target levels of
      office and home BP should be <130/80 mm Hg and <125/75 mm Hg, respectively, in
      T2DM patients. Considering more favorable metabolic profiles and renoprotective
      effects than other classes of antihypertensive agents, angiotensin-converting
      enzyme inhibitors and angiotensin II receptor blockers are recommended as the
      first-line therapy for patients with hypertension and T2DM in JSH 2014. However,
      the target BP and the first-line therapy remain controversial because of the
      paucity of high-quality evidence with consistency. It is suggested that BP
      management should be tailored for each patient with T2DM, based on tolerability
      and considerations of comorbidity.

PMID- 28446811
TI  - Rheumatoid arthritis: Obesity skews markers of inflammation.

PMID- 28446812
TI  - 'Does ________ predict neurodevelopmental impairment in former preterm infants?'
      Is this the right question to be asked?

PMID- 28446810
TI  - Pathogenesis of ankylosing spondylitis - recent advances and future directions.
AB  - Over the past 5 years, advances in high-throughput techniques and studies
      involving large cohorts of patients have led to considerable advances in the
      identification of novel genetic associations and immune pathways involved in
      ankylosing spondylitis (AS). These discoveries include genes encoding cytokine
      receptors, transcription factors, signalling molecules and transport proteins.
      Although progress has been made in understanding the functions and potential
      pathogenic roles of some of these molecules, much work remains to be done to
      comprehend their complex interactions and therapeutic potential in AS. In this
      Review, we outline the current knowledge of AS pathogenesis, including genetic
      risk associations, HLA-B27-mediated pathology, perturbations in antigen
      presentation pathways and the contribution of the type 3 immune response.

PMID- 28446813
TI  - Context-specific roles of EMT programmes in cancer cell dissemination.
AB  - The role of the epithelial-to-mesenchymal transition in tumour progression
      remains a topic of intense debate. Now, data on the role of Zeb1 in the
      metastatic spread of pancreatic cancer clarify apparently conflicting views by
      revealing context-specific, differential use of individual epithelial-to
      mesenchymal transition transcription factors in cancer cell dissemination.

PMID- 28446814
TI  - Science in the age of Trump.

PMID- 28446815
TI  - Terminating the replication helicase.
AB  - A feature of the cell cycle is that the events of one cycle must be reset before
      the next one begins. A study now shows that the replication machinery is removed
      from fully replicated DNA by a conserved ubiquitin- and CDC48 (also known as p97)
      dependent pathway. This explains how eukaryotic chromosomes are returned to the
      unreplicated state.

PMID- 28446816
TI  - SIRT2 and glycolytic enzyme acetylation in pluripotent stem cells.
AB  - The metabolic transition from mitochondrial oxidative phosphorylation (OXPHOS) to
      glycolysis is critical for somatic reprogramming of induced pluripotent stem
      cells (iPSCs). SIRT2 has now been established as a previously unknown regulator
      of this metabolic transition during somatic reprogramming by controlling the
      acetylation status of glycolytic enzymes.

PMID- 28446819
TI  - Foreword celebrating the career of Professor Satoshi Omura.

PMID- 28446818
TI  - Metabolic changes promote rejection of oncogenic cells.
AB  - Dysfunctional cells are eliminated from epithelial monolayers by a process known
      as cell extrusion to maintain tissue homeostasis. Normal epithelial cells are now
      shown to induce the extrusion of oncogene-transformed cells by inducing metabolic
      changes in the oncogene-expressing cells through PDK4-mediated inhibition of PDH
      and mitochondrial metabolism.

PMID- 28446817
TI  - Shh-mediated centrosomal recruitment of PKA promotes symmetric proliferative
      neuroepithelial cell division.
AB  - Tight control of the balance between self-expanding symmetric and self-renewing
      asymmetric neural progenitor divisions is crucial to regulate the number of cells
      in the developing central nervous system. We recently demonstrated that Sonic
      hedgehog (Shh) signalling is required for the expansion of motor neuron
      progenitors by maintaining symmetric divisions. Here we show that activation of
      Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric
      recruitment of PKA to the centrosomes that nucleate the mitotic spindle,
      maintaining symmetric proliferative divisions. Notably, Shh signalling
      upregulates the expression of pericentrin, which is required to dock PKA to the
      centrosomes, which in turn exerts a positive feedback onto Shh signalling. Thus,
      by controlling centrosomal protein assembly, we propose that Shh signalling
      overcomes the intrinsic asymmetry at the centrosome during neuroepithelial cell
      division, thereby promoting self-expanding symmetric divisions and the expansion
      of the progenitor pool.

PMID- 28446820
TI  - Achievements of Professor Satoshi Omura.

PMID- 28446821
TI  - Message from a long-time friend: congratulations on Emeritus Professor Satoshi
      Omura's accomplishments.

PMID- 28446822
TI  - Anti-Mycobacterium activity of microbial peptides in a silkworm infection model
      with Mycobacterium smegmatis.
AB  - An in vivo-mimic silkworm infection model with Mycobacterium smegmatis was
      established. When silkworms were raised at 37  degrees C following an injection
      of M. smegmatis cells (1.25 * 107 CFU larva-1 g-1) into the silkworm hemolymph,
      they died within 48 h. Under these conditions, four microbial peptides with anti
      M. smegmatis activity, lariatin A, calpinactam, lysocin E and propeptin, exerted
      therapeutic effects in a dose-dependent manner, and these are also clinically
      used agents that are active against Mycobacterium tuberculosis. These results
      indicate that the silkworm infection model with M. smegmatis is practically
      useful for the screening of therapeutically effective anti-M. tuberculosis
      antibiotics.

PMID- 28446823
TI  - Potential Data Sources for a New Study of Social Mobility in the United States.

PMID- 28446825
TI  - Vaidyavallabha: An Authoritative Work on Ayurveda Therapeutics.
AB  - The text "Vaidyavallabha" is an authoritative work on Ayurvedic therapeutics
      written by Hastiruci, a Jain scholar. It belongs to the time period of 1673-1726
      CE. Different physical and mental ailments with their treatments are addressed in
      the 274 verses spanned over eight chapters in this work. In this text many
      unique, special and simple medicinal preparations for different diseases are
      given. Many drugs which were easily available in the local area are given much
      more importance in the treatment. Added to this, method and uniqueness of naming
      the diseases in the text stand differently when compared to other texts. Even
      though the text seems to be small, the contribution to the field of Ayurveda
      practice is priceless.

PMID- 28446824
TI  - The Translational Framework of Ayurveda as a Knowledge System.

PMID- 28446826
TI  - A Systematic and Mechanistic Review on the Phytopharmacological Properties of
      Alhagi Species.
AB  - Alhagi species are well known in Iran (locally known as Khar Shotor) and other
      parts of Asia as a popular folk medicine. Recent research has shown extensive
      pharmacological effects of these species. This paper is a comprehensive review of
      the phytopharmacological effects and traditional uses of Alhagi species and their
      active constituents with special attention to the responsible mechanisms,
      effective dosages and routes of administration. The Alhagi species studied in
      this paper include: A. maurorum, A. camelorum, A. persarum, A. pseudoalhagi, and
      A. kirgisorum. In order to include all the up to date data, the authors went
      through several databases including the Web of Science, Embase, etc. The findings
      were critically reviewed and sorted on the basis of relevance to the topic.
      Tables have been used to clearly present the ideas and discrepancies were settled
      through discussion. Alhagi species have significant biomedical properties which
      can be exploited in clinical use. Proantocyanidin isolated from A. pseudoalhagi
      has significant biochemical effects on blood factors. Among Alhagi species, A.
      camelorum and A. maurorum possess the highest anti-microbial activity. Most of
      the effects observed with A. maurorum are dose-dependent. This paper indicates
      with emphasis that Alhagi species are safe and rich sources of biologically
      active compounds with low toxicity. Since DNA damage has been observed following
      the ingestion of specific concentrations of A. pseudalhagi, care should be taken
      during administration of the plant for therapeutic use. Further studies are
      required to confirm the safety and quality of these plants to be used by
      clinicians as therapeutic agents.

PMID- 28446828
TI  - Preliminary Pharmacognostic and Phytochemical Investigation of Blepharis sindica
      T. Anders Seeds.
AB  - BACKGROUND: Blepharis sindica - T. Anders of family Acanthaceae is an important
      medicinal plant which is mainly used as an invigorating tonic, given to cattle to
      increase milk production and its roots are used for urinary discharge and
      dysmenorrhea. It is commonly known as "Bhangari". It is extensively used
      traditionally as Vajikaraka and Vrsya (Aphrodisiac) by vaidyas of Rajasthan and
      Gujarat. The seeds of Blepharis sindica T. Anders are the parts of the plant
      valued for their medicinal value. AIMS: The present investigation deals with the
      pharmacognostic studies of the root, stem, seed and seed powder. MATERIALS AND
      METHODS: The study includes macroscopy, microscopy, preliminary phytochemical
      analysis and physicochemical evaluation using methods given in Indian Ayurvedic
      Pharmacopoeia. RESULTS: Physicochemical parameters such as total ash value, acid
      insoluble ash value and water soluble ash value were determined to be 21.449 +/-
      2.629%w/w, 0.986%w/w, 18.746%w/w respectively. Preliminary phytochemical analysis
      of extracts were carried out. Different extracts contain carbohydrate, protein,
      alkaloids, phenols, saponins and steroids prominently. Calcium, zinc, potassium
      and iron were also present. These secondary metabolites are the active
      constituents and may be responsible for B. sindica's pharmacological activities.
      Chief characters of transverse section of stem include ringed vascular bundles,
      radial striped pith rays and parenchymal pith. Seed shows presence of scalariform
      tracheids and lignified walls. CONCLUSIONS: The result of the present study can
      be useful for the identification and preparation of a monograph of the plant.

PMID- 28446827
TI  - Effects of Various Pranayama on Cardiovascular and Autonomic Variables.
AB  - Cardiovascular functions are controlled by neural factors, temperature, hormones,
      etc., Of these, neural factors primarily concern the autonomic nervous system,
      which plays a major role in maintaining and regulating cardiac functions, e.g.,
      blood pressure and heart rate. Pranayama is one of the most important yogic
      practices. There are various review articles on Yoga and its effects but, though
      Pranayama is a part of yoga, there is lack of review articles. To the best of our
      knowledge there is no known review article on effect of various Pranayama on
      cardiovascular and autonomic variables. To provide a general overview about the
      effect of various pranayama (breathing techniques) on cardiovascular and
      autonomic variables. A narrative review was performed based on the available
      scientific literature. An electronic data search was performed in Medline/PubMed
      database to review relevant articles, using keywords such as "Pranayama, Yogic
      breathing techniques, Unilateral nostril breathing, Alternate nostril breathing,
      Kapalbhati, Bhastrika and Bhramari Pranayama". All the relevant articles
      published from 1988 to 06-04-2016 were included in this review. Slow type of
      yogic breathing technique was reported to produce beneficial effect on
      cardiovascular and autonomic variables while fast breathing techniques do not
      produce such effects. There is lack of consistency in the results of specific
      nostril yogic breathing techniques and the mechanisms behind the effects of
      various pranayama. This review suggests that different types of Pranayama
      techniques produce different effects and the mechanisms behind these effects are
      not fully understood.

PMID- 28446829
TI  - Experimental Evaluation of Hingvadi Ghrta in Behavioral Despair Using Animal
      Models.
AB  - CONTEXT: Depression, a sustained mood disorder caused by selective diminution of
      specialized cells in brain is increasing at an alarming rate. It will be the
      second largest morbid illness by next decade and is the leading cause of suicidal
      deaths. The available antidepressant medications benefit only a third of its
      recipients and have many side effects. Hence, it is imperative to search in
      Ayurveda for leads. AIM: To evaluate Anti- depressant activity of Hingvadi Ghrta
      in vivo . SETTINGS AND DESIGN: Comparative preclinical study. MATERIALS AND
      METHODS: Hingvadi Ghrta (HG) was prepared using standard operating procedure,
      physicochemically analyzed and assessed. Tail Suspension Test (TST) model with
      Swiss albino mice and Forced Swim Test (FST) model with Wistar albino rats were
      used to assess anti-depressant activity. Imipramine hydrochloride in dose of 15
      mg/kg for TST and 10 mg/kg for FST, was the standard drug and Ghee as vehicle
      control in dose of 0.1g/20g for TST and 0.72g/200g for FST orally. Hingvadi Ghrta
      in doses of 0.05g/20g (x/2), 0.1g/20g (x) and 0.2 g/20g (2x) for TST and
      0.36g/200g (x/2), 0.72g/200g (x) and 1.44g/200g (2x) for FST was administered to
      3 test groups for 21 days orally except Plain control group which received only
      distilled water. Duration of immobility in seconds for TST and number of
      rotations for FST were noted for assessment. STATISTICAL ANALYSIS USED: One way
      ANOVA followed by Dunnets test and Paired t test. RESULTS: HG was significantly
      effective at dose of 0.1gm/20gm for TST (P = 0.0037; P < 0.01) and 0.72g/200g for
      FST (P = 0.0055, P < 0.01) comparable to Imipramine hydrochloride. CONCLUSIONS:
      HG displayed potent anti depressant activity comparable to standard drug
      Imipramine Hydrochloride.

PMID- 28446830
TI  - Bryophyllum pinnatum Leaf Extracts Prevent Formation of Renal Calculi in
      Lithiatic Rats.
AB  - BACKGROUND: Bryophyllum pinnatum, commonly known as Pattharcatta, is used
      traditionally in ethnomedicinal practices for the treatment of kidney stone and
      urinary insufficiency. AIM: The present study evaluated the effect of Bryophyllum
      pinnatum on ethylene glycol (EG)-induced renal calculi in rats. MATERIALS AND
      METHODS: Renal calculi were induced in rats by administration of 0.75% EG in
      drinking water and co-treated orally with standard drug, Cystone (750 mg/kg), or
      alcoholic and hydro-alcoholic extracts in doses of 100, 200 and 400 mg/kg for 28
      days. Weekly body weights were recorded. On day 29, urolithiasis was confirmed by
      assessing the urinary parameters (urine volume, pH, uric acid, calcium,
      phosphorus, oxalate, magnesium and creatinine clearance), serum biochemical
      parameters (creatinine, uric acid, urea, calcium, phosphorus and magnesium),
      oxidative stress parameters and histology of kidney. RESULTS: Treatment with
      extracts attenuated the EG-induced decrease in body weight and elevation in
      urinary parameters (uric acid, calcium, phosphorus and oxalate) and serum
      biochemical parameters (creatinine, uric acid, urea, calcium, phosphorus and
      magnesium). Extract treatment also reversed EG-induced decrease in urine volume,
      pH, magnesium and creatinine clearance, oxidative and histological damages in
      kidneys. Results were comparable to standard drug, Cystone. Results indicated
      that EG administration caused renal calculi formation which is prevented by
      treatment with extracts. The observed antilithiatic effect may be attributed to
      the presence of high content of phenolics, flavonoids and saponins in the
      extracts. CONCLUSION: Bryophyllum pinnatum leaves showed preventive effect
      against renal calculi formation and validates its ethnomedicinal use in urinary
      disorders. It further supports its therapeutic potential for the treatment of
      urinary calculi.

PMID- 28446831
TI  - Antinociceptive and Antioxidant Activities of the Methanolic Extract of Telfairia
      occidentalis Seeds.
AB  - CONTEXT: The seeds of Telfairia occidentalis have been known to possess different
      biological properties and are used in traditional medicine in Africa and Asia to
      treat many ailments. The plant is particularly noted traditionally for its
      healing properties and is usually consumed in the form of herbal
      decoctions/concoctions as a blood tonic, to treat sudden attacks of convulsions,
      pain, malaria and anaemia. AIMS: In the present study, various phytochemical and
      pharmacological studies were done on the methanolic extract of the seeds of
      Telfairia occidentalis to evaluate its antioxidant and antinociceptive properties
      to substantiate its traditional use. METHODS: Phytochemical screening of the
      extract was done according to standard procedures. Antioxidant potential was
      ascertained using 2,2-diphenyl-1-picryl hydrazyl (DPPH) scavenging activity,
      total phenolic content and total flavonoid content assays. Analgesic activity was
      analyzed using formalin induced paw licking test in albino rats at 100, 200 and
      400 mg extract per kg body weight. STATISTICAL ANALYSIS USED: All results
      extrapolated from the experiments were expressed as mean +/- SEM. Data obtained
      was analyzed statistically using ANOVA (one-way) followed by Dennett's posthoc
      test. RESULTS: Phytochemicals present in the extract were alkaloids, flavonoids,
      saponins, terpenoids, steroid and anthraquinones. The extract significantly
      inhibited DPPH scavenging activity with percentage inhibition of 147.3%. The
      methanolic seed extract of T. occidentalis significantly reduced (P < 0.05)
      formalin induced paw licking in both neurogenic and inflammatory phases of
      formalin induced paw licking test, with 35.59 and 78.51% inhibition at 400 mg/kg,
      in albino rats in a dose dependent manner. CONCLUSIONS: The seed extract in this
      study significantly reduced formalin induced hind paw licking, and could be used
      as an analgesic for treatment of pain and also showed marked antioxidant
      potential.

PMID- 28446832
TI  - Taila Daha (Cauterization with Oil) an Innovative Approach in Pilonidal Sinus.
AB  - Summary: Pilonidal sinus is a chronic inflammatory track in mid gluteal cleft
      usually associated with hairs with an incidence rate of twenty six per one lakh
      population. It is more prevalently seen in the natal cleft of hairy middle aged
      obese, males. Such type of non-healing tracts may be considered as Nadivrana
      (Sinuses) and can either be treated by the conventional Ksarasutra (medicated
      seton) therapy or contemporary treatment methods. Irrespective of whatsoever
      management protocol adopted, it inevitably needs long term hospitalisation and is
      associated with complications. A case of a 28 year old male patient, presenting
      with pain (within tolerable limits) in the natal cleft and frequent occurrence of
      a pustule which burst out spontaneously on and off, diagnosed as pilonidal sinus
      (nadi vrana) was treated with excision of tract and Tailadaha (thermal
      cauterization with hot oil) with a combination of yastimadhu taila and powdered
      Copper Sulphate (CuSO4). Good haemostasis and uneventful wound healing with a
      minimally invasive and cost effective treatment was the outcome of study. This
      study represents an innovative treatment modality in pilonidal sinus.

PMID- 28446833
TI  - The effects of invasive pests and pathogens on strategies for forest
      diversification.
AB  - Diversification of the tree species composition of production forests is a
      frequently advocated strategy to increase resilience to pests and pathogens;
      however, there is a lack of a general framework to analyse the impact of economic
      and biological conditions on the optimal planting strategy in the presence of
      tree disease. To meet this need we use a novel bioeconomic model to
      quantitatively assess the effect of tree disease on the optimal planting
      proportion of two tree species. We find that diversifying the species composition
      can reduce the economic loss from disease even when the benefit from the
      resistant species is small. However, this key result is sensitive to a pathogen's
      characteristics (probability of arrival, time of arrival, rate of spread of
      infection) and the losses (damage of the disease to the susceptible species and
      reduced benefit of planting the resistant species). This study provides an
      exemplar framework which can be used to help understand the effect of a pathogen
      on forest management strategies.

PMID- 28446835
TI  - Fitness and return to work challenges for occupational health physician.

PMID- 28446834
TI  - The Intimate Geographies of Panic Disorder: Parsing Anxiety through
      Psychopharmacological Dissection.
AB  - The category of panic disorder was significantly indebted to early
      psychopharmacological experiments (in the late 1950s and early 1960s) by the
      psychiatrist Donald Klein, in collaboration with Max Fink. Klein's technique of
      "psychopharmacological dissection" underpinned his transformation of clinical
      accounts of anxiety and was central in effecting the shift from agoraphobic
      anxiety (with its spatial imaginary of city squares and streets) to panic. This
      technique disaggregated the previously unitary affect of anxiety-as advanced in
      psychoanalytic accounts-into two physiological and phenomenological kinds.
      "Psychopharmacological dissection" depended on particular modes of clinical
      observation to assess drug action and to interpret patient behavior. The
      "intimate geographies" out of which panic disorder emerged comprised both the
      socio-spatial dynamics of observation on the psychiatric ward and Klein's use of
      John Bowlby's model of separation anxiety-as it played out between the dyad of
      infant and mother-to interpret his adult patients' affectively disordered
      behavior. This essay, in offering a historical geography of mid-twentieth-century
      anxiety and panic, emphasizes the importance of socio-spatial setting in
      understanding how clinical and scientific experimentation opens up new ways in
      which affects can be expressed, shaped, observed, and understood.

PMID- 28446836
TI  - Physical activity levels and prevalence of low back pain in Thai call-center
      operators.
AB  - BACKGROUND: Call-center operators are exposed to working conditions that indicate
      an increased risk of developing musculoskeletal disorders. Nevertheless, there
      are few studies regarding health and working condition in call-center operators.
      Thus, this study was designed to investigate the physical activity levels and
      prevalence of low back pain (LBP) in Thai call-center operators. MATERIALS AND
      METHODS: A self-reported questionnaire was distributed to 150 operators at a call
      center to identify the physical activity levels, prevalence of LBP, personal
      characteristics, and associated work factors. RESULTS: The questionnaire response
      rate was 70% (n = 105). The participants' age was 27.8 +/- 3.1 years, height was
      159.97 +/- 6.26 cm, weight was 52.89 +/- 12.89 kg, and females 86.7% (n = 91),
      and males 13.3% (n = 14). Participants worked at least 6 days every week, with an
      average of 8 hours each day. Sixty-one percent of them worked over time with an
      average 2 h/day. Forty percent of the participants had no exercise; 34.3%
      exercised 1-2 times/week. Those who did physical exercise spent less than 30
      min/time. The overall self-reported prevalence of LBP was 65.7%, and they
      reported high severity of LBP for 42.9%. All participants reported that their LBP
      as recurring, and 62.9% reported that LBP was aggravating by sitting during
      working hours. CONCLUSION: The call-center operators had a sedentary work style.
      The majority of operators in this study had low level of physical activity and
      suffered from low back pain. The prevalence of low back pain was associated to
      their level of physical activity and work factors.

PMID- 28446837
TI  - Level of stress and its determinants among Intensive Care Unit staff.
AB  - CONTEXT: Stress is a usual and normal part of our daily lives. It is a normal
      physical reaction to an internal or external pressure that is placed on a
      person's system. Extended periods of stress can cause destructive changes in the
      body. OBJECTIVES: (1) To assess the prevalence of stress and its level among
      intensive care unit (ICU) staff (doctors and nurses) of various hospitals and (2)
      to correlate the level of stress with certain variables. SETTINGS AND DESIGN: A
      cross-sectional study was conducted in the ICU of various hospital of Pune for a
      period of 1 month. MATERIALS AND METHODS: Eighty-two ICU staff (doctors and
      nurses) were contacted and interviewed using pretested proforma containing DASS
      stress rating scale (for stress only). STATISTICAL ANALYSIS USED: Data analysis
      was performed using the Statistical Package for the Sciences (SPSS) version 19.0
      software. To compare the level of stress with various parameters, we used Chi
      square test. P value <0.05 was considered to be significant. RESULTS: The overall
      prevalence of stress among ICU staff (doctors and nurses) was 52.43%. Prevalence
      of stress among ICU doctors was 36.58% and nurses was 68.29%. According to the
      DASS (for stress only), 19.51% doctors were mildly stressed, 14.63% were
      moderately stressed, and 2.44% were severely stressed. Among nurses, 48.78% were
      mildly stressed and 19.51% were moderately stressed. CONCLUSIONS: The result
      indicated that prevalence of stress among ICU staff (doctors and nurses) is high.

PMID- 28446838
TI  - Visual functions of workers exposed to organic solvents in petrochemical
      industries.
AB  - AIM: The purpose of this study was to evaluate the visual functions of workers
      exposed to organic solvents in petrochemical industries. MATERIALS AND METHODS:
      Thirty workers from the petroleum refinery and 30 age-matched controls (mean age)
      were recruited. Visual functions and occupational exposure levels were assessed
      among both the groups. Visual acuity, contrast sensitivity, color vision, and
      visual fields were evaluated at the workplace. The biological samples, namely
      blood and urine, were collected at the workplace and transported to the
      laboratory for analysis. The urinary excretion of hippuric and methylhippuric
      acid as well as creatinine was measured by high performance liquid
      chromatography. RESULTS: The mean age of the workers and controls were 39.7 +/-
      7.6 years and 38.6 +/- 8.1, years respectively. The mean years of experience of
      the workers were 15.6 +/- 6.8 years. Visual acuity was >0.01 LogMAR among both
      the control and case groups. The contrast sensitivity was reduced at 12cpd among
      workers. Comparison between groups was done using independent sample t-test. The
      mean difference in color confusion index was 0.11 +/- 0.05 (P = 0.037*). The mean
      difference in visual fields was -0.31 +/- 0.36 dB (P = 0.933). The mean
      difference in urinary hippuric acid level (urinary metabolite of toluene) between
      the groups was 0.19 +/- 0.96 g/g creatinine (P = 0.049FNx01). The mean difference
      in the excretion of methylhippuric acid (urinary metabolite of xylene) was 0.06
      +/- 0.04g/g creatinine (P = 0.154). We also found that exposure was a significant
      risk factor for color vision defect with an odds ratio of 4.43 (95% CI: 1.36
      14.4); P = 0.013. CONCLUSION: The study results showed that contrast sensitivity
      and color vision were affected among workers in petrochemical industry.

PMID- 28446839
TI  - Awareness of blood-borne infections and burden of occupational exposures to blood
      and body fluids among health care personnel in a tertiary care teaching hospital.
AB  - BACKGROUND AND OBJECTIVES: Occupational exposures (OEs) to blood and body fluids
      (BBFs) pose significant risk of transmission of blood-borne infections (BBIs) to
      health care personnel (HCP) and are grossly underreported. We aimed to study the
      awareness of BBIs and their prevention, burden of OEs, assess factors
      contributing to them and their poor reporting and assess the practices for their
      prevention among HCP. MATERIALS AND METHODS: This cross-sectional study conducted
      at a tertiary care teaching hospital located in south India used a self
      administered questionnaire to assess the awareness of BBIs, attitude and practice
      of HCP for prevention of OEs, and to quantify the burden of exposures. All
      formally self-reported OEs during the study period of 2 years were documented
      prospectively. RESULTS: Majority (369/401, 92%) of HCP surveyed had fair general
      awareness of BBIs. Though 90% were aware of the concept of universal precautions
      (UPs), self-reported adherence to barrier precautions was acceptable in only 80%.
      Overall, 56% and 46% of HCP were aware of human immunodeficiency virus (HIV) and
      hepatitis B post-exposure prophylaxis (PEP) respectively. Eighteen percent
      (74/401) were either not vaccinated or incompletely vaccinated against hepatitis
      B. Recapping of used needles was reported by 79% (317/401). Nearly half (208/401)
      reported OEs over preceding year and 70% (146/208) of exposed had not formally
      reported them. Over the 2-year study period, 53 formally self-reported exposures
      were documented prospectively. Needle stick injuries accounted for 83% of the
      exposures, and appropriate personal protective devices were not being used during
      47% of exposures. Though doctors had the highest awareness, they reported lowest
      adherence to barrier precautions and highest burden of exposures (P < 0.05).
      CONCLUSION: Though majority of HCP had fair awareness of BBIs, it did not
      translate into adequate adherence to UPs and safe practices. High burden of OEs
      and their poor reporting emphasize the need to motivate our HCP to adhere to safe
      work practices and to promptly seek professional counselling after exposures.
      There is an urgent need to educate HCP about the availability and effectiveness
      of PEP for HIV and hepatitis B. A uniform national policy for prevention and
      reporting of OEs has to be framed.

PMID- 28446840
TI  - Musculoskeletal morbidity among construction workers: A cross-sectional community
      based study.
AB  - BACKGROUND: Construction industry is one of the stable growing industries in
      India. People working in construction industries are at a risk of various
      occupational diseases. Musculoskeletal disorder (MSD) is the single largest cause
      of work-related illness, accounting for over 33% of all newly reported
      occupational illnesses in the general population and approximately 77% in
      construction workers. In spite of the high prevalence and wide range of adverse
      consequences, the studies highlighting the burden and impact of musculoskeletal
      morbidities are very scarce in India. The current study is aimed at filling this
      vital gap in the current knowledge. OBJECTIVE: To assess the musculoskeletal
      morbidities among construction workers using the modified Nordisk Scale.
      MATERIALS AND METHODS: A cross-sectional community-based study was conducted by
      30 * 10 multistage cluster random sampling method in Chennai Metropolitan city.
      RESULTS: Out of the 308 participants included in the final analysis, majority
      were 21-40 years. Working hours ranged from 8 to 12 hours. Duration of work
      ranged from 2 months to 20 years. Out of 308 participants, 104 workers (33.8%)
      had musculoskeletal problems. Three most common disorders discovered were low
      backache seen in 64 (20.8%), shoulder pain seen in 36 (11.7%), and wrist pain
      seen in 36 (11.7%) participants. The proportion of hospitalized participants in
      the last 1 year was 7.8%. Total duration in the construction field, duration of
      work hours, and higher age had statistically significant impact on
      musculoskeletal morbidity. CONCLUSION: The prevalence of musculoskeletal
      morbidity was very high in construction workers, with resulting adverse impact on
      the workers. Immense attention, in the form of appropriate prevention measures,
      is needed to effectively address this public health problem.

PMID- 28446841
TI  - Occupation-related chromium toxicity a rare cause of renal failure and
      rhabdomyolysis.
AB  - A 21-year-old gentleman, a worker in a mobile phone shop, was admitted with
      rhabdomyolysis, renal failure, and pulmonary edema requiring mechanical
      ventilation and hemodialysis. After extensive workup and ruling out other causes,
      heavy metal poisoning was considered. Investigations during the course of the
      hospital stay revealed chromium poisoning. With repeated hemodialysis, his
      parameters normalized and he was discharged home in a stable condition. Diagnosis
      of chromium toxicity needs high index of suspicion. A history of occupational
      exposure might offer a clue to diagnosis. With hemodialysis and supportive care,
      it is a potentially salvageable condition.

PMID- 28446842
TI  - Choosing controls in a case control study.

PMID- 28446843
TI  - A class of generalized invex functions and vector variational-like inequalities.
AB  - In this paper, a class of generalized invex functions, called [Formula: see text]
      invex functions, is introduced, and some examples are presented to illustrate
      their existence. Then we consider the relationships of solutions between two
      types of vector variational-like inequalities and multi-objective programming
      problem. Finally, the existence results for the discussed variational-like
      inequalities are proposed by using the KKM-Fan theorem.

PMID- 28446844
TI  - Certain inequalities involving the k-Struve function.
AB  - We aim to introduce a k-Struve function and investigate its various properties,
      including mainly certain inequalities associated with this function. One of the
      inequalities given here is pointed out to be related to the so-called classical
      Turan-type inequality. We also present a differential equation, several
      recurrence relations, and integral representations for this k-Struve function.

PMID- 28446845
TI  - Why is the Acute Watery Diarrhea in Ethiopia Attaining Extended Course?

PMID- 28446846
TI  - Insulin Sensitivity and Plasma Glucose Response to Aerobic Exercise in Pregnant
      Women at Risk for Gestational Diabetes Mellitus.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is one of the common
      complications that occur during pregnancy. Early intervention is essential to
      prevent the development of the disease in the non-pregnant state but also helpful
      in preventing the occurrence of GDM. The aim of the study was to assess the
      effect of aerobic exercises on insulin sensitivity and fasting plasma glucose
      level in pregnant women with risk for gestational diabetes mellitus. MATERIALS
      AND METHODS: Forty multigravidae women between 20-24 weeks of gestation with risk
      for GDM were randomly selected (age range was 25-35 years), body mass index
      ranged from 30-35 kg/m2. Women were divided into two equal groups: intervention
      group (A), which followed an aerobic exercise program in the form of walking on
      treadmill, three times weekly until the end of 37 weeks of gestation in addition
      to diet control. Control group (B) which received diet control with usual care
      given by obstetricians and midwives. Evaluation of the women in both groups was
      carried out before and after treatment program through assessment of fasting
      blood glucose and insulin levels. RESULTS: There was a highly statistically
      significance decrease in fasting blood glucose level, fasting insulin level in
      both groups where the p value was 0.0001 favoring group (A). CONCLUSION: Moderate
      intensity of aerobic exercises were effective in reducing fasting blood glucose
      level and fasting insulin level in pregnant women with risk for gestational
      diabetes mellitus.

PMID- 28446847
TI  - Knowledge, Experiences and Training Needs of Health Professionals about Disaster
      Preparedness and Response in Southwest Ethiopia: a cross sectional study.
AB  - BACKGROUND: Over the past decade, the magnitude and intensity of disasters have
      been vividly rising globally due to the forces of nature or man. This study aimed
      at assessing the perceived knowledge, experiences and training needs of health
      professionals regarding disasters, their prevention and management in Jimma Zone,
      Southwest Ethiopia. METHODS: An institution based cross-sectional survey was
      conducted on 377 health professionals taken from 9 randomly selected districts
      out of 18. All health professionals working at health offices, hospitals and
      health centers were included. Data were collected using a structured
      questionnaire which was developed by the investigators after reviewing the
      relevant literature in the field. Data were coded and entered into SPSS 20
      software for cleaning and analysis. Descriptive and logistic regression analyses
      were done. RESULTS: The majority (85.1%) of the participants were able to define
      the concept of disaster from various perspectives; 9.7% did not know about it at
      all and 5.2% could describe the concept partially or misconceived it. The
      majority (84.3%) agreed that disaster has direct public health consequences on
      humans. The main public health consequence of disaster the participants mentioned
      was environmental pollution (65.8%). Malaria, measles and diarrhoeal diseases
      accounted for 35.5%, 33.1% and 10.5% of the epidemics, respectively. Only 20.6%
      of the respondents were trained on disaster related topics in the last two years.
      The majority felt that they had poor knowledge on early warning indicators of
      drought (48.0%) and flood (48.0%). Simialry, 50.8%, 47.7%, 51.1% and 42.6% of the
      participants had poor knowledge on preparedness to drought, preparedness to
      flood, response to drought, response to flood. On composite scale, they generally
      perceived to have adequate (29.4%), moderate (32.4%) and poor (38.2%) knowledge
      about early warning information bout, preparedness for and response to common
      disasters. A vast majority (92.8%) reported that they need training on disaster
      preparedness, management and response. CONCLUSION: A considerable number of
      professionals had limited understanding about the concept of disaster and
      response to certain specific disasters. They also had limited opportunities for
      training, despite their felt needs. Therefore, training should be provided
      focusing on the specific gaps identified.

PMID- 28446848
TI  - Seroepidemiology Study of Cytomegalovirus and Rubella among Pregnant Women at St.
      Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Maternal cytomegalovirus (CMV) and rubella infections have adverse
      neonatal outcomes. Both CMV and rubella are more widespread in developing
      countries and in communities with lower socioeconomic status. The aim of this
      study was to investigate sero-prevalence of CMV and rubella infection and
      associated possible risk factors. METHOD: Using cross sectional study design a
      total of 200 pregnant women were consecutively recruited starting from June and
      July 2014. Blood samples were collected, and structured questions were used to
      gather socio-demographic and risk factor related data. ELISA was used to detect
      CMV (IgG, IgM) and rubella IgM. SPSS version 20 was used to analyze the data, and
      regression was also performed. RESULTS: Out of 200 pregnant women, 88.5%,
      30(15.5%) and 4(2.0%) were CMV-IgG, CMV-IgM, and rubella-IgM positive,
      respectively. Women who were immune/positive only for IgG were 73.5%. The second
      group was those with primary infection [IgG (+) plus IgM (+)] and this consisted
      of 15.0% participants. Eleven percent of the participants were at high risk for
      primary infection during their pregnancy. One pregnant woman was identified as
      having a recent primary infection. In this study, no statistically significant
      association was detected between CMV infection with idependent factors (p
      value>0.05). CONCLUSION: In addition to detection of high prevalence of CMV,
      detecting recent infection of rubella worsens the outcome of the disease. Rubella
      vaccine should be taken into consideration after large scale surveillance.
      However, screening of all pregnant women for CMV infection may not be cost
      effective as in the countries with high seropositivity.

PMID- 28446850
TI  - Readiness of Health Centers and Primary Hospitals for the Implementation of
      Proposed Health Insurance Schemes in Southwest Ethiopia.
AB  - BACKGROUND: In response to the 2005 World Health Assembly, many low income
      countries developed different healthcare financing mechanisms with risk pooling
      stategy to ensure universal coverage of health services. Accordingly, service
      availability and readiness of the health system to bear the responsibility of
      providing service have critical importance. The objective of this study was to
      assess service availability and readiness of health centers and primary hospitals
      to bear the responsibility of providing service for the members of health
      insurance schemes. METHODS AND MATERIALS: A facility based cross sectional study
      design with quantitative data collection methods was employed. Of the total 18
      districts in Jimma Zone, 6(33.3%) districts were selected randomly. In the
      selected districts, there were 21 functional public health facilities (health
      centers and primary hospitals) which were included in the study. Data were
      collected by interviewer administered questionnaire. Descriptive statistics were
      calculated by using SPSS version 20.0. Prior to data collection, ethical
      clearance was obtained. RESULTS: Among the total 21 public health facilities
      surveyed, only 38.1% had all the categories of health professionals as compared
      to the national standards. The majority, 85.2%, of the facilities fulfilled the
      criteria for basic equipment, but 47.7% of the facilities did not fulfill the
      criteria for infection prevention supplies. Moreover, only two facilities
      fulfilled the criteria for laboratory services, and 95.2% of the facilities had
      no units/departmenst to coordinate the health insurance schemes. CONCLUSIONS:
      More than nine out of ten facilities did not fulfill the criteria for providing
      healthcare services for insurance beneficiaries and are not ready to provide
      general services according to the standard. Hence, policy makers and implementers
      should devise strategies to fill the identified gaps for successful and
      sustainable implementation of the proposed insurance scheme.

PMID- 28446849
TI  - Effect of Male Partner's Support on Spousal Modern Contraception in a Low
      Resource Setting.
AB  - BACKGROUND: As efforts continue to increase contraceptive uptake, male partner
      support remains important in spousal modern contraceptive use. METHODS: A
      prospective cross-sectional survey involving women on modern contraception was
      conducted at the family planning clinic of the University of Ilorin Teaching
      Hospital, Nigeria, between December 2013 and April 2014. All consenting
      participants completed a self-administered questionnaire designed for the study,
      and statistical analysis was done with SPSS version 20.0 using with chi square
      test and logistic regression; p value <0.05 was significant. RESULTS: There were
      305 participants: 208(68.2%) were multipara, the commonest current and previous
      contraceptives used were IUD and injectables while male partner was responsible
      for discontinuation in 30(23.3%) of previous users. Covert contraceptive use was
      22(7.2%), male partner support was 209(68.5%) as payment for the contraceptives
      (203; 66.6%) or transportation to the clinic (198; 64.9%). Also, 55(18.0%) women
      failed to comply with contraception recently due to male partner hindrance (25;
      45.5%) or inability to pay for contraceptive (11; 20%) or transportation to the
      clinic (8; 14.5%). Male partners hindered contraception by reporting the woman to
      relatives/friends (8; 32%) or denying her money for feeding allowance (6; 24%);
      277(90.8%) women want contraception to be couple decision while 261(85.6%) want
      contraception administered only if both partners consented. The significant
      predictors of male partner support were awareness about the contraceptive use
      (p<0.001, OR0.114; CI0.041-0.319), level of education (p0.007, OR1.488; CI1.114
      1.9870) and social class (p0.029, OR0.690; CI0.495-0.963). CONCLUSION: Male
      partner hindrances and costs of contraceptive or transportation to clinic are
      important in noncompliance. Male partner education, subsidized/free
      contraceptives and mobile/community services will improve compliance.

PMID- 28446852
TI  - Clinical Performance of Emergency Surgical Officers in Southern Ethiopia.
AB  - BACKGROUND: Serious shortage of gynecologists and surgeons for several decades
      leading to a three-year masters level training was initiated in 2009. However,
      systematic analysis was not done to assess the graduates' performance. The
      purpose of this study was to assess improvement in access to emergency surgical
      and obstetrical care services. METHODS: Both quantitative and qualitative methods
      were employed to assess the competence of emergency surgical officers (ESOs) in
      their decision making and surgical skills in eight hospitals between 2012 and
      2014. Anesthesia time, post-operative hospital stay and change in hemoglobin
      level were, among others, used as proxy indicators of their surgical skills.
      RESULTS: A total of 4075 obstetric and surgical operations was performed in the
      study hospitals. Of which, 93% were done on emergency base. Of the total
      emergency procedures, 3570(94%) were done by ESOs. Nearly two-thirds (63%) of all
      the emergency operations were cesarean sections, which were done by ESOs. Out of
      239 uterine ruptures, hysterectomy was done for 58%. The proportion of cesarean
      and instrumental deliveries over the total deliveries were 13% and 0.7%,
      respectively. Explorative laparotomies and appendectomies were the majority of
      the non-obstetric emergency operations. Interviewed staff in the respective
      hospitals stated that ESOs' clinical decision making, surgical skill and
      commitment to discharge their responsibilities were in the best possible.
      CONCLUSIONS: The study showed that deployment of ESOs made the emergency surgery
      services accessible to the majority, and their clinical decision making and
      surgical skills were remarkable.

PMID- 28446851
TI  - An Invitro Evaluation of the Accuracy of Two Electronic Apex Locators to
      Determine Working Length in the Presence of Various Irrigants.
AB  - BACKGROUND: Cleaning and shaping of root canal system requires various irrigating
      solutions. The question is whether the presence of irrigation solution alters
      working length determination using apex locators. The purpose of this study was
      to compare the accuracy of Root ZX and i-Root apex locator for determining
      working length in the presence of different irrigating solution. MATERIALS AND
      METHOD: Eighty extracted single rooted human teeth were used. The teeth were
      sectioned at Cemento Enamel Junction (CEJ) and actual canal length determined.
      Then, working length measurements were obtained using Root ZX and i-Root apex
      locator in the presence of irrigating solutions namely 0.9% saline, 3% of sodium
      hypochlorite (NaOCl), 2% chlorhexidine digluconate(CHX) and 17% Ethylene Diamine
      Tetra Acetic acid (EDTA). The measurements obtained with Root ZX and i-Root apex
      locator were compared with actual canal length and subjected to statistical
      analysis using Post Hoc Test Tukey's Method. RESULTS: This study revealed that
      both the tested Electronic apex locators (EAL) were able to measure the canal
      length in the presence of tested irrigating solutions. The presence of irrigating
      solutions of saline, NaOCl, chlorhexidine and EDTA in the root canal marginally
      influenced the accuracy of the Root ZX or i-Root (P < 0.36), but with no clinical
      significance. CONCLUSION: Root ZX and i-Root can be used safely to determine
      working length in the presence of various irrigants. The content of the root
      canal did not influence the accuracy while measuring working length using
      Electronic apex locators (EAL).

PMID- 28446854
TI  - Plasma Malondialdehyde (MDA): An Indication of Liver Damage in Women with Pre
      Eclamsia.
AB  - BACKGROUND: One of the features associated with pre-eclampsia is elevated liver
      transaminases. The reason this happens has not been fully described. However, the
      hepatocytes are not known to be spared by free radical injury. This study was
      conducted to examine the relationship between product of free radical injury
      (malondialdehyde) and transaminases in pre-eclamptic women. PATIENTS AND METHODS:
      A total of 98 and 115 pre-eclamptic and apparently normal pregnant women were
      selected from the booking clinic of Ladoke Akintola University of Technology
      Teaching Hospital, Osogbo. Non-pregnant women were selected from volunteered
      members of staff. Malondialdehyde (MDA), aspartate transaminase (AST) and alanine
      transaminase (ALT) analyses were determined on collected venous blood sample.
      Statistical analyses of variables were done using SPSS 17 taking level of
      significance to be p<0.05. RESULTS: Subjects with plasma AST between 10 and 20U/L
      had mean plasma MDA of 0.92umol/l whereas those with plasma levels greater than
      41U/L had mean plasma MDA of 4.72umol/l. Similarly, Subjects with plasma ALT
      between 10 and 20U/L had mean plasma MDA of 0.86umol/l, and subjects with plasma
      ALT greater than 51 U/L had mean plasma MDA of 4.71umol/l. Positive correlation
      was observed between AST and ALT(r=0.79; p=0.047), between AST and MDA(r=0.690;
      p=0.061) as well as between ALT and MDA(r=0.571; p=0.049). CONCLUSION: The
      elevated liver enzymes seen in women with pre-eclampsia may be due to free
      radical injury to the liver. Pre-eclamptic women without free radical injury did
      not have elevated transaminases.

PMID- 28446853
TI  - The Role of Health Extension Workers in Linking Pregnant Women With Health
      Facilities for Delivery in Rural and Pastoralist Areas of Ethiopia.
AB  - BACKGROUND: Women's preference to give birth at home is deeply embedded in
      Ethiopian culture. Many women only go to health facilities if they have
      complications during birth. Health Extension Workers (HEWs) have been deployed to
      improve the utilization of maternal health services by bridging the gap between
      communities and health facilities. This study examined the barriers and
      facilitators for HEWs as they refer women to mid-level health facilities for
      birth. METHODS: A qualitative study was conducted in three regions: Afar Region,
      Southern Nations Nationalities and People's Region and Tigray Region between
      March to December 2014. Interviews and focus group discussions were conducted
      with 45 HEWs, 14 women extension workers (employed by Afar Pastoralist
      Development Association, Afar Region) and 11 other health workers from health
      centers, hospitals or health offices. Data analysis was done based on collating
      the data and identifying key themes. RESULTS: Barriers to health facilities
      included distance, lack of transportation, sociocultural factors and
      disrespectful care. Facilitators for facility-based deliveries included liaising
      with Health Development Army (HDA) leaders to refer women before their expected
      due date or if labour starts at home; the introduction of ambulance services;
      and, provision of health services that are culturally more acceptable for women.
      CONCLUSION: HEWs can effectively refer more women to give birth in health
      facilities when the HDA is well established, when health staff provide respectful
      care, and when ambulance is available at any time.

PMID- 28446855
TI  - Eosinophilic Granuloma in Jaw Bone: A Pare Pediatric Case Report.
AB  - BACKGROUND: Eosinophilic granuloma (EG), one of the three clinical forms of
      Langerhans cell histiocytosis (LCH), is a benign inflammatory reaction to an
      unknown etiologic agent. It most commonly occurs in children and young adults.
      The most frequently involved bones are the skull, the ribs and the femurs.
      Alongside the cranium, the maxilla and mandible can also be affected. CASE
      DETAILS: Herein, we report a case of eosinophilic granuloma in a ten years old
      boy involving posterior quadrants upper and lower jaws as a destructive lesion
      involving gingiva, periodontium and alveolar bone. Involvement of other bones is
      ruled out by nucleotide imaging study. CONCLUSION: EG should be considered as a
      differential diagnosis whenever there is a bony destructive lesion involving
      alveolar bone of the Jaws. Early diagnosis and surgical intervention will resolve
      the lesion.

PMID- 28446856
TI  - Big Keratocystic Odontogenic Tumor of the Mandible: A Case Report.
AB  - BACKGROUND: Keratocystic odontogenic tumor (KCOT) is a rare, benign, intraosseous
      tumor of odontogenic origin with a potential of aggressive and infiltrative
      behavior. It shows specific histopathological features, and has a high recurrence
      rate. CASE DETAILS: The presented case was of a 30 years old man from South
      Ethiopia, with a giant keratocystic odontogenic tumor of the mandible.
      CONCLUSIONS: Although the occurrence of KCOT is rare, attention should be given
      during its clinical diagnosis. In this report, we presented the aggressive
      surgical management of a KCOT in a 30 years old patient with no evidence of
      recurrence within six monthsof follow-up.

PMID- 28446857
TI  - Hemolytic Anemia Caused by Kinking of Dacron Grafts Implanted in Repair of after
      Aortic Dissection.
AB  - BACKGROUND: Hemolytic anemia caused by a kinked Dacron graft is a rare
      complication after repair of acute aortic dissection. We present a case of
      hemolytic anemia due to kinking of previously implanted Dacron graft for
      ascending aorta dissection treated by surgery and replaced with new Dacron. CASE
      DETAILS: We report a case of postoperative hemolytic anemia with kinking of the
      graft at the outer graft layer and intra luminal bulging of the inner graft.
      Postoperative computed tomography showed Dacron graft kinking at the mid part of
      the graft. Transthoracic echocardiography (TTE) revealed good function of repair
      aortic valve. Upon the redo midsternotomy, we found moderate kinking of the graft
      at the outer graft layer and intra luminal bulging of the inner graft. We
      performed reconstruction of the aortic root with a new Dacron. CONCLUSION: The
      careful literature review showed that there are some few cases of hemolytic
      anemia after dissection, but no cases in which hemolytic anemia occurred in a
      patient with kinked Dacron graft after surgery delete treated by replacement of
      kinked Dacron graft by new one.

PMID- 28446858
TI  - A Case of Autoimmune Polyglandular Syndrome .ype 2 Associated with Atypical Form
      of Scleromyxedema.
AB  - BACKGROUND: Autoimmune polyglandular syndrome type 2 represents an uncommon
      endocrine disorder composed by Addison's disease with autoimmune thyroid disease
      (Schmidt's syndrome) and/or type 1 diabetes mellitus. Scleromyxedema is a rare
      progressive cutaneous mucinosis usually associated with systemic involvement and
      paraproteinemia. To the best of our knowledge, there is no case report of
      Schmidt's syndrome associated with scleromyxedema. CASE DETAILS: A 34-year-old
      woman was admitted to Donetsk Clinical Territorial Medical Association due to
      acute general weakness, reduced vision, dryness of integuments, memory decline,
      fatigue, weight loss, rash on the face trunk and extremities. A diagnosis of APS
      type II was made comprising of autoimmune hypothyroidism and autoimmune adrenal
      insufficiency. Skin histopathologic examination demonstrated the presence of
      mucin deposits, dermal fibrosis, fibrocytes and perivascular inflammation. In the
      absence of monoclonal paraproteinemia and the presence of typical histological
      and clinical signs, an atypical form of scleromyxedema was diagnosed. The patient
      was administered a lifetime replacement levothyroxine and methylprednisolone
      therapy. CONCLUSION: Identification and adequate treatment of both APS type II
      and scleromyxedema in affected patients pose a problem due to the lack of
      facilities for diagnosis and management plus common misdiagnosis. Early diagnosis
      should be made before the development of life-threatening complications.

PMID- 28446859
TI  - Divergent Task Performance in Older Adults: Declarative Memory or Creative
      Potential?
AB  - Divergent thinking is the ability to produce a range of responses or solutions
      and is an element of creative processing. Divergent thinking requires
      disengagement, the ability to associate between words or ideas, and the
      production of responses. Lesion and imaging studies have shown frontal-lobe
      involvement for these activities, and frontal lobe function is highly dependent
      on white matter pathways. Normal aging often results in deficits in functions
      controlled by the frontal lobes as well as decrements in white matter
      connectivity. The objectives of this study were to compare non time-constrained
      tasks of verbal divergent processing in young adults (YAs) and older adults (OAs)
      and correlate performance with tasks of working memory, language ability, and
      disengagement/inhibition. Participants were 30 YAs and 30 OAs. Contrary to the a
      priori hypothesis, OAs produced significantly more unique responses than YAs,
      although total fluency was not significantly different. Correlational analyses
      examining the groups together and separately revealed a number of differences
      suggesting that the groups were utilizing different underlying cognitive
      abilities to complete these tasks. The authors propose that the primary factor
      resulting in higher uniqueness scores for the OAs was a greater wealth of
      experience as well as longer exposure to language use.

PMID- 28446860
TI  - UVB promotes the initiation of uveitic inflammatory injury in vivo and is
      attenuated by UV-blocking protection.
AB  - PURPOSE: Uveitic inflammatory injury can cause irreversible visual loss; however,
      no single animal model recapitulates all the characteristics of human uveitis.
      Ultraviolet radiation (UVR) is one of the risk factors for uveitis, but the role
      of UVR in the pathogenesis of uveitic injury is unclear. The aim of this study
      was to elucidate whether UVB promotes the initiation of, and subsequently
      contributes to, uveitic inflammatory injury. METHODS: Mice were assigned to
      either a blank control group or one of three UVB treatment groups: no protection,
      protection with Nelfilcon A contact lens (Food and Drug Administration [FDA]
      class II, about 46.8% UVB transmittance), or protection with Etafilcon A contact
      lens (FDA class IV, about 0.55% UVB transmittance). The contact lenses acted as
      blocking barriers against UVR. After the application of UVR, pathologic injuries
      were determined with slit-lamp microscopy and histologic examination. RESULTS:
      Compared with the intact status of the controls, the anterior eyes of the UVB
      groups showed pathologic alterations in physiologic properties and tissue
      integrity. UVR promoted anterior uveitic inflammatory injury, with expansion of
      the hyperemic iris vessels, over-production of aqueous humor protein, disruption
      of the blood-aqueous barrier, and embedding of infiltrative leukocytes inside the
      iridocorneal angle. However, blockage of UVR in vivo retarded the progression of
      uveitic inflammatory injury. The highest level of UV protection in the Etafilcon
      A group resulted in greater inhibition of uveitic inflammatory injury than that
      in the Nelfilcon A group. CONCLUSIONS: This study demonstrates that UVB initiated
      and promoted uveitic inflammatory injury. UV protection is needed for the
      clinical management of anterior uveitis. The Etafilcon A lenses provide better
      protection of the anterior segment of the eye against UVB damage compared with
      the Nelfilcon A lenses.

PMID- 28446861
TI  - Ethnic Identity, Questionnaire Content, and the Dilemma of Race Matching in
      Surveys of African Americans by African American Interviewers.
AB  - We used data from two telephone-administered health surveys to explore African
      Americans' preferences for interviewer race. The first survey utilized African
      American interviewers to assess ethnic identity and aspects of healthy eating
      among 617 African American adults. In the second survey, interviewers of varying
      races queried 534 African American adults about their motivations to eat
      healthier. The motivation survey contained almost no racial content, whereas 40%
      of the ethnic identity survey assessed racial content. Using ethnic identity
      survey data only, we found that respondents with Afrocentric or Black American
      identity components were more likely to prefer African American interviewers than
      respondents with solely Assimilated, Bicultural, or Multicultural identity
      components. Ethnic identity survey respondents were also more likely to prefer
      racially/ethnically matched interviewers than motivation survey respondents.
      Ethnic identity respondents with a college or graduate degree reported lower
      hypothetical comfort with a White interviewer than respondents with a high school
      education.

PMID- 28446864
TI  - Neural Entrainment to Polyrhythms: A Comparison of Musicians and Non-musicians.
AB  - Music can be thought of as a dynamic path over time. In most cases, the rhythmic
      structure of this path, such as specific sequences of strong and weak beats or
      recurring patterns, allows us to predict what and particularly when sounds are
      going to happen. Without this ability we would not be able to entrain body
      movements to music, like we do when we dance. By combining EEG and behavioral
      measures, the current study provides evidence illustrating the importance of
      ongoing neural oscillations at beat-related frequencies-i.e., neural entrainment
      for tracking and predicting musical rhythms. Participants (13 musicians and 13
      non-musicians) listened to drum rhythms that switched from a quadruple rhythm to
      a 3-over-4 polyrhythm. After a silent period of ~2-3 s, participants had to
      decide whether a target stimulus was presented on time with the triple beat of
      the polyrhythm, too early, or too late. Results showed that neural oscillations
      reflected the rhythmic structure of both the simple quadruple rhythm and the more
      complex polyrhythm with no differences between musicians and non-musicians.
      During silent periods, the observation of time-frequency plots and more commonly
      used frequency spectra analyses suggest that beat-related neural oscillations
      were more pronounced in musicians compared to non-musicians. Neural oscillations
      during silent periods are not driven by an external input and therefore are
      thought to reflect top-down controlled endogenous neural entrainment. The
      functional relevance of endogenous neural entrainment was demonstrated by a
      positive correlation between the amplitude of task-relevant neural oscillations
      during silent periods and the number of correctly identified target stimuli. In
      sum, our findings add to the evidence supporting the neural resonance theory of
      pulse and meter. Furthermore, they indicate that beat-related top-down controlled
      neural oscillations can exist without external stimulation and suggest that those
      endogenous oscillations are strengthened by musical expertise. Finally, this
      study shows that the analysis of neural oscillations can be a useful tool to
      assess how we perceive and process complex auditory stimuli such as polyrhythms.

PMID- 28446865
TI  - Enhanced Expression of Markers for Astrocytes in the Brain of a Line of GFAP-TK
      Transgenic Mice.
AB  - GFAP-TK mice are widely used in studies on neurogenesis and reactive astrocytes.
      Previous studies reported that GCV treatment in GFAP-TK mice resulted in reduced
      neurogenesis and deletion of proliferating GFAP-expressing astrocytes without
      affecting mature GFAP-expressing astrocytes. In the present study, we found that
      GFAP- and vimentin-expressing astrocytes were dramatically increased in the
      cortex and hippocampus with or without GCV treatment in a line of GFAP-TK mice
      (Jackson Laboratory, Stock No. 005698), while the neurons and microglia were not
      affected. In a second line of GFAP-TK mice (MMRRC, Stock No. 037351-UNC)
      generated in Dr. Heather Cameron's laboratory in NIH, however, no difference in
      GFAP and vimentin expression was found in both hippocampus and cortex, regardless
      of GCV treatment or not. Furthermore, enhanced expression of aquaporin 4 (AQP4)
      was found in the cortex and hippocampus of the GFAP-TK mice from Jackson lab but
      not in the brain of GFAP-TK mice from NIH. Our data suggested that we should be
      careful to select different lines of GFAP-TK mice to study adult neurogenesis or
      reactive astrocytes.

PMID- 28446863
TI  - Peptides as Quorum Sensing Molecules: Measurement Techniques and Obtained Levels
      In vitro and In vivo.
AB  - The expression of certain bacterial genes is regulated in a cell-density
      dependent way, a phenomenon called quorum sensing. Both Gram-negative and Gram
      positive bacteria use this type of communication, though the signal molecules
      (auto-inducers) used by them differ between both groups: Gram-negative bacteria
      use predominantly N-acyl homoserine lacton (AHL) molecules (autoinducer-1, AI-1)
      while Gram-positive bacteria use mainly peptides (autoinducer peptides, AIP or
      quorum sensing peptides). These quorum sensing molecules are not only involved in
      the inter-microbial communication, but can also possibly cross-talk directly or
      indirectly with their host. This review summarizes the currently applied
      analytical approaches for quorum sensing identification and quantification with
      additionally summarizing the experimentally found in vivo concentrations of these
      molecules in humans.

PMID- 28446866
TI  - The Contribution of Immune Infiltrates to Ototoxicity and Cochlear Hair Cell
      Loss.
AB  - Cells of the immune system have been shown to infiltrate the cochlea after
      acoustic trauma or ototoxic drug treatment; however, the contribution of the
      immune system to hair cell loss in the inner ear is incompletely understood. Most
      studies have concentrated on the immediate innate response to hair cell damage
      using CD45 as a broad marker for all immune cells. More recent studies have used
      RNA sequencing, GeneChip arrays and quantitative PCR to analyze gene expression
      in the entire cochlea after auditory trauma, leading to a better understanding of
      the chemokines and cytokines that attract immune cells to the cochlea. Immune
      suppression by blocking cytokines or immune receptors has been proven to suppress
      hair cell damage. However, it is now understood that not all immune cells are
      detrimental to the cochlea. CX3CR1+ resident macrophages protect hair cells from
      damage mediated by infiltrating immune cells. Systemically, the immune response
      is associated with both protection and pathology, and it has been implicated in
      the regeneration of certain tissues after injury. This review focuses on the
      studies of immune cells in various models of hearing loss and highlights the
      steps that can be taken to elucidate the connection between the immune response
      and hearing loss. The interplay between the immune system and tissues that were
      previously thought to be immune privileged, such as the cochlea, is an emerging
      research field, to which additional studies of the immune component of the
      cochlear response to injury will make an important contribution.

PMID- 28446867
TI  - Response Properties of Motor Equivalence Neurons of the Primate Premotor Cortex.
AB  - To study the response properties of cells that could participate in eye-hand
      coordination we trained two macaque monkeys to perform center-out saccades and
      pointing movements with their right or left forelimb toward visual targets
      presented on a video display. We analyzed the phasic movement related discharges
      of neurons of the periarcuate cortex that fire before and during saccades and
      movements of the hand whether accompanied by movements of the other effector or
      not. Because such cells could encode an abstract form of the desired displacement
      vector without regard to the effector that would execute the movement we refer to
      such cells as motor equivalence neurons (Meq). Most of them (75%) were found in
      or near the smooth pursuit region and the grasp related region in the caudal bank
      of the arcuate sulcus. The onset of their phasic discharges preceded saccades by
      about 70 ms and hand movements by about 150 ms and was often correlated to both
      the onset of saccades and the onset of hand movements. The on-direction of Meq
      cells was uniformly distributed without preference for ipsiversive or
      contraversive movements. In about half of the Meq cells the preferred direction
      for saccades was the preferred direction for hand movements as well. In the
      remaining cells the difference was considerable (>90 deg), and the on-direction
      for eye-hand movements resembled that for isolated saccades in some cells and for
      isolated hand movements in others. A three layer neural network model that used
      Meq cells as its input layer showed that the combination of effector invariant
      discharges with non-invariant discharges could help reduce the number of decoding
      errors when the network attempts to compute the correct movement metrics of the
      right effector.

PMID- 28446868
TI  - Triggering Avoidance: Dissociable Influences of Aversive Pavlovian Conditioned
      Stimuli on Human Instrumental Behavior.
AB  - The present study investigates human aversive Pavlovian-to-Instrumental Transfer
      (PIT) and possible influences of outcome devaluation and instrumental
      overtraining on this effect. PIT measures the extent to which a Pavlovian
      conditioned stimulus (CS) can increase instrumental responses independently
      paired with the same (outcome-specific transfer) or a different (general
      transfer) reinforcer. Two measures of PIT were obtained: the percentage of
      instrumental responses and the vigor of such responses. Thirty-eight volunteers
      performed a standard PIT task sequence. Results showed a double dissociation
      between outcome-specific and general transfer: the first selectively expressed in
      the amount of responses, the second in the vigor measure solely. Furthermore,
      outcome-specific transfer was enhanced by overtraining, but not affected by
      devaluation. General transfer, on the other hand, was affected by neither
      overtraining, nor devaluation. A positive correlation between general transfer
      and sensitivity to punishments was found. Findings are discussed in terms of
      hypothetically different underlying neurobehavioral mechanisms and their
      relations to habits and goal-directed behavior.

PMID- 28446869
TI  - fNIRS Studies on Hemispheric Asymmetry in Atypical Neural Function in
      Developmental Disorders.
AB  - Functional lateralization is highly replicable trait of human neural system. Many
      previous studies have indicated the possibility that people with attention
      deficits/hyperactivity-disorder (ADHD) and autism spectrum disorder (ASD) show
      hemispheric asymmetry in atypical neural function. However, despite the abundance
      of relevant studies, there is still ongoing controversy over this issue. In the
      present mini-review, we provide an overview of the hemispheric asymmetry in
      atypical neural function observed in fNIRS studies on people with these
      conditions. Atypical neural function is defined as group-difference in the task
      related concentration change of oxygenated hemoglobin. The existing fNIRS studies
      give support to the right-lateralized atypicalty in children with ADHD. At the
      same time, we did not find clear leftward-lateralization in atypical activation
      in people with ASD. On the basis of these, we discuss the current states and
      limitation of the existing studies.

PMID- 28446870
TI  - A Randomized Controlled ERP Study on the Effects of Multi-Domain Cognitive
      Training and Task Difficulty on Task Switching Performance in Older Adults.
AB  - Executive functions are subject to a marked age-related decline, but have been
      shown to benefit from cognitive training interventions. As of yet, it is,
      however, still relatively unclear which neural mechanism can mediate training
      related performance gains. In the present electrophysiological study, we examined
      the effects of multi-domain cognitive training on performance in an untrained cue
      based task switch paradigm featuring Stroop color words: participants either had
      to indicate the word meaning of Stroop stimuli (word task) or perform the more
      difficult task of color naming (color task). One-hundred and three older adults
      (>65 years old) were randomly assigned to a training group receiving a 4-month
      multi-domain cognitive training, a passive no-contact control group or an active
      (social) control group receiving a 4-month relaxation training. For all groups,
      we recorded performance and EEG measures before and after the intervention. For
      the cognitive training group, but not for the two control groups, we observed an
      increase in response accuracy at posttest, irrespective of task and trial type.
      No training-related effects on reaction times were found. Cognitive training was
      also associated with an overall increase in N2 amplitude and a decrease of P2
      latency on single trials. Training-related performance gains were thus likely
      mediated by an enhancement of response selection and improved access to relevant
      stimulus-response mappings. Additionally, cognitive training was associated with
      an amplitude decrease in the time window of the target-locked P3 at fronto
      central electrodes. An increase in the switch positivity during advance task
      preparation emerged after both cognitive and relaxation training. Training
      related behavioral and event-related potential (ERP) effects were not modulated
      by task difficulty. The data suggest that cognitive training increased slow
      negative potentials during target processing which enhanced the N2 and reduced a
      subsequent P3-like component on both switch and non-switch trials and
      irrespective of task difficulty. Our findings further corroborate the
      effectiveness of multi-domain cognitive training in older adults and indicate
      that ERPs can be instrumental in uncovering the neural processes underlying
      training-related performance gains.

PMID- 28446871
TI  - Prevalence of Joint Gait Patterns Defined by a Delphi Consensus Study Is Related
      to Gross Motor Function, Topographical Classification, Weakness, and Spasticity,
      in Children with Cerebral Palsy.
AB  - During a Delphi consensus study, a new joint gait classification system was
      developed for children with cerebral palsy (CP). This system, whose reliability
      and content validity have previously been established, identified 49 distinct
      joint patterns. The present study aims to provide a first insight toward the
      construct validity and clinical relevance of this classification system. The
      retrospective sample of convenience consisted of 286 patients with spastic CP (3
      18 years old, GMFCS levels I-III, 166 with bilateral CP). Kinematic and kinetic
      trials from three-dimensional gait analysis were classified according to the
      definitions of the Delphi study, and one classified trial was randomly selected
      for each included limb (n = 446). Muscle weakness and spasticity were assessed
      for different muscle groups acting around the hip, knee, and ankle. Subsequently,
      Pearson Chi square tests, Cramer's V, and adjusted standardized residuals were
      calculated to explore the strength and direction of the associations between the
      joint patterns, and the different patient-specific characteristics (i.e., age,
      GMFCS level, and topographical classification) or clinical symptoms (muscle
      weakness and spasticity). Patient-specific characteristics showed several
      significant associations with the patterns of different joints, but the strength
      of most identified associations was weak. Apart from the knee during stance phase
      and the pelvis in the sagittal plane, the results systematically showed that the
      patterns with "minor gait deviations" were the most frequently observed. These
      minor deviations were found significantly more often in limbs with a lower level
      of spasticity and good muscle strength. Several other pathological joint patterns
      were moderately associated with weakness or spasticity, including but not limited
      to "outtoeing" for weakness and "intoeing" for spasticity. For the joints in the
      sagittal plane, significantly stronger associations were found with muscle
      weakness and spasticity, possibly because most of the evaluated muscles in this
      study mainly perform sagittal plane motions. Remarkably, the hip patterns in the
      coronal plane did not associate significantly with any of the investigated
      variables. Although further validation is warranted, this study contributes to
      the construct validity of the joint patterns of the Delphi consensus study, by
      demonstrating their ability to distinguish between clinically relevant subgroups
      in CP.

PMID- 28446872
TI  - A Neurocomputational Model of Goal-Directed Navigation in Insect-Inspired
      Artificial Agents.
AB  - Despite their small size, insect brains are able to produce robust and efficient
      navigation in complex environments. Specifically in social insects, such as ants
      and bees, these navigational capabilities are guided by orientation directing
      vectors generated by a process called path integration. During this process, they
      integrate compass and odometric cues to estimate their current location as a
      vector, called the home vector for guiding them back home on a straight path.
      They further acquire and retrieve path integration-based vector memories globally
      to the nest or based on visual landmarks. Although existing computational models
      reproduced similar behaviors, a neurocomputational model of vector navigation
      including the acquisition of vector representations has not been described
      before. Here we present a model of neural mechanisms in a modular closed-loop
      control-enabling vector navigation in artificial agents. The model consists of a
      path integration mechanism, reward-modulated global learning, random search, and
      action selection. The path integration mechanism integrates compass and odometric
      cues to compute a vectorial representation of the agent's current location as
      neural activity patterns in circular arrays. A reward-modulated learning rule
      enables the acquisition of vector memories by associating the local food reward
      with the path integration state. A motor output is computed based on the
      combination of vector memories and random exploration. In simulation, we show
      that the neural mechanisms enable robust homing and localization, even in the
      presence of external sensory noise. The proposed learning rules lead to goal
      directed navigation and route formation performed under realistic conditions.
      Consequently, we provide a novel approach for vector learning and navigation in a
      simulated, situated agent linking behavioral observations to their possible
      underlying neural substrates.

PMID- 28446873
TI  - Novel VPS13A Gene Mutations Identified in Patients Diagnosed with Chorea
      acanthocytosis (ChAc): Case Presentation and Literature Review.
AB  - Chorea-acanthocytosis (ChAc) is a rare autosomal recessive inherited syndrome
      characterized by hyperkinetic movements, seizures, cognitive impairment,
      neuropsychiatric symptoms, elevated serum biochemical indicators and acanthocytes
      detection in peripheral blood smear. Vacuolar protein sorting 13A (VPS13A) gene
      mutations have been proven to be genetically responsible for the pathogenesis of
      ChAc. Herein, based on the typical clinical symptoms and neuroimaging features,
      we present two suspected ChAc cases which are further genetically confirmed by
      four novel VPS13A gene mutations. Nevertheless, the sharp contrast between the
      population base and published ChAc reports implies that ChAc is considerably
      underdiagnosed in China. Therefore, we conclude several suggestive features and
      propose a diagnostic path of ChAc from a clinical, genetic and neuroimaging
      perspective, aiming to facilitate the diagnosis and management of ChAc in China.

PMID- 28446874
TI  - Age-Related Differences in Reorganization of Functional Connectivity for a Dual
      Task with Increasing Postural Destabilization.
AB  - The aged brain may not make good use of central resources, so dual task
      performance may be degraded. From the brain connectome perspective, this study
      investigated dual task deficits of older adults that lead to task failure of a
      suprapostural motor task with increasing postural destabilization. Twelve younger
      (mean age: 25.3 years) and 12 older (mean age: 65.8 years) adults executed a
      designated force-matching task from a level-surface or a stabilometer board.
      Force-matching error, stance sway, and event-related potential (ERP) in the
      preparatory period were measured. The force-matching accuracy and the size of
      postural sway of the older adults tended to be more vulnerable to stance
      configuration than that of the young adults, although both groups consistently
      showed greater attentional investment on the postural task as sway regularity
      increased in the stabilometer condition. In terms of the synchronization
      likelihood (SL) of the ERP, both younger and older adults had net increases in
      the strengths of the functional connectivity in the whole brain and in the fronto
      sensorimotor network in the stabilometer condition. Also, the SL in the fronto
      sensorimotor network of the older adults was greater than that of the young
      adults for both stance conditions. However, unlike the young adults, the older
      adults did not exhibit concurrent deactivation of the functional connectivity of
      the left temporal-parietal-occipital network for postural-suprapostural task with
      increasing postural load. In addition, the older adults potentiated functional
      connectivity of the right prefrontal area to cope with concurrent force-matching
      with increasing postural load. In conclusion, despite a universal negative effect
      on brain volume conduction, our preliminary results showed that the older adults
      were still capable of increasing allocation of neural sources, particularly via
      compensatory recruitment of the right prefrontal loop, for concurrent force
      matching under the challenging postural condition. Nevertheless, dual-task
      performance of the older adults tended to be more vulnerable to postural load
      than that of the younger adults, in relation to inferior neural economy or a slow
      adaptation process to stance destabilization for scant dissociation of control
      hubs in the temporal-parietal-occipital cortex.

PMID- 28446876
TI  - Hypersensitivity to Carboplatin in Children with Malignancy.
AB  - Purpose: Carboplatin-based regimens have proven efficacy in children with cancer.
      However, the development of hypersensitivity reactions (HSRs) may have a negative
      impact on treatment intensity and patients' outcome. The aim of this review is to
      summarize the incidence and the clinical features of HSRs occurring in children
      with cancer treated with carboplatin and their impact on treatment efficacy.
      Methods: Data were collected by searching for relevant studies on the incidence,
      clinical features and management of possible side effects about the use of
      carboplatin in children, published from March 1987 to October 2016 in the PubMed
      database. Results: Carboplatin HSRs present with mild/moderate to severe clinical
      patterns. The risk of HSR is related to the cumulative number of infusions.
      Moreover, a greater risk of developing an HSR has been observed in younger
      patients than in older age groups of children; risk is also greater in girls and
      in patients with a prior history of allergy to other drugs. Management options
      include cessation of carboplatin and switching to another agent, premedication
      with antihistamines and/or corticosteroids, and carboplatin desensitization. For
      sensitized patients who have obtained benefits from carboplatin, the continuation
      of the treatment is desirable and desensitization protocols have showed promising
      results. Conclusion: Clinicians must not underestimate the potential risk and
      occurrence of carboplatin HSRs in the pediatric population in order to outline
      adequate management strategies. Desensitization protocols should be considered
      for patients sensitive to carboplatin in order to avoid having to discontinue an
      effective chemotherapy.

PMID- 28446875
TI  - Cannabinoid Modulation of Memory Consolidation in Rats: Beyond the Role of
      Cannabinoid Receptor Subtype 1.
AB  - The effects induced by exogenous manipulation of endocannabinoid
      neurotransmission on emotion and memory are often contradictory. Among the
      different factors involved, of particular interest is the binding affinity of
      endocannabinoids, and their analogs, for other receptor families beyond
      cannabinoid receptors, such as the peroxisome proliferator-activated receptors
      (PPARs), and the transient receptor potential cation channel subfamily V member 1
      (TRPV1). The aim of this study was to investigate which receptor subtype mediates
      cannabinoid effects on memory consolidation for emotionally arousing experiences.
      We tested two cannabinoid compounds with different pharmacological properties in
      the inhibitory avoidance task, and evaluated whether the observed effects are
      mediated by cannabinoid, PPARalpha or TRPV1 receptor activation. We found that
      the synthetic cannabinoid agonist WIN55,212-2 and the FAAH inhibitor URB597 both
      enhanced memory consolidation for inhibitory avoidance training. WIN55,212-22
      effects on memory consolidation were predominantly mediated by CB1 receptor
      activation but CB2 receptors were involved as well. The URB597-induced memory
      enhancement was dependent on the activation not only of CB1 and CB2 receptors
      but, notwithstanding, PPAR-alpha and TRPV1 receptors were involved as well. Our
      findings drive beyond the classical hypothesis centered on the unique role of CB1
      receptor activation for cannabinoid effects on memory, and reveal new insights in
      the neural mechanisms of memory consolidation.

PMID- 28446877
TI  - Exploring the Role of CYP3A4 Mediated Drug Metabolism in the Pharmacological
      Modulation of Nitric Oxide Production.
AB  - Nitric-oxide synthase, the enzyme responsible for mammalian nitric oxide
      generation, and cytochrome P450, the major enzymes involved in drug metabolism,
      share striking similarities. Therefore, it makes sense that cytochrome P450 drug
      mediated biotransformations might play an important role in the pharmacological
      modulation of nitric oxide synthase. In this work, we have undertaken an
      integrated in vitro assessment of the hepatic metabolism and nitric oxide
      modulation of previously described dual inhibitors (imidazoles and macrolides) of
      these enzymes in order assess the implication of CYP450 activities over
      production of nitric oxide. In vitro systems based in human liver microsomes and
      activated mouse macrophages were developed for these purposes. Additionally in
      vitro production the hepatic metabolites of dual inhibitor, roxithromycin, was
      investigated achieving the identification and isolation of main hepatic
      biotransformation products. Our results suggested that for some macrolide
      compounds, the cytochrome P450 3A4 derived drug metabolites have an important
      effect on nitric oxide production and might critically contribute to the
      pharmacological immunomodulatory activity observed.

PMID- 28446879
TI  - The Mammalian Peptide Adrenomedullin Acts as a Growth Factor in Tobacco Plants.
AB  - Growth factors are extracellular signals that regulate cell proliferation and
      total body mass. Some animal growth factors can work on plant tissues and vice
      versa. Here we show that the mammalian growth factor adrenomedullin (AM) induces
      growth in tobacco plants. Addition of synthetic AM resulted in a dose-dependent
      growth of tobacco calluses. Furthermore, AM transgenic plants showed enhanced
      survival and significant increases in stem diameter, plant height, leaf length,
      weight of all organs, and a reduction in the time to flowering when compared to
      plants transformed with the control vector. These differences were maintained
      when organs were dried, resulting in a mean total biomass increase of 21.3%. The
      levels of soluble sugars and proteins in the leaves were unchanged between
      genotypes. AM transgenic plants had a significantly higher expression of cyclin
      D3 and the transcription factor E2FB than controls, suggesting that cell cycle
      regulation may be part of the intracellular signaling of AM in plants. In
      summary, mammalian AM increases vascular plants' survival and biomass with no
      apparent detriment of plant's morphological and/or biochemical properties, thus
      this strategy could be useful for crop productivity improvement.

PMID- 28446878
TI  - Computational Model Predicts the Effects of Targeting Cellular Metabolism in
      Pancreatic Cancer.
AB  - Reprogramming of energy metabolism is a hallmark of cancer that enables the
      cancer cells to meet the increased energetic requirements due to uncontrolled
      proliferation. One prominent example is pancreatic ductal adenocarcinoma, an
      aggressive form of cancer with an overall 5-year survival rate of 5%. The
      reprogramming mechanism in pancreatic cancer involves deregulated uptake of
      glucose and glutamine and other opportunistic modes of satisfying energetic
      demands in a hypoxic and nutrient-poor environment. In the current study, we
      apply systems biology approaches to enable a better understanding of the dynamics
      of the distinct metabolic alterations in KRAS-mediated pancreatic cancer, with
      the goal of impeding early cell proliferation by identifying the optimal
      metabolic enzymes to target. We have constructed a kinetic model of metabolism
      represented as a set of ordinary differential equations that describe time
      evolution of the metabolite concentrations in glycolysis, glutaminolysis,
      tricarboxylic acid cycle and the pentose phosphate pathway. The model is
      comprised of 46 metabolites and 53 reactions. The mathematical model is fit to
      published enzyme knockdown experimental data. We then applied the model to
      perform in silico enzyme modulations and evaluate the effects on cell
      proliferation. Our work identifies potential combinations of enzyme knockdown,
      metabolite inhibition, and extracellular conditions that impede cell
      proliferation. Excitingly, the model predicts novel targets that can be tested
      experimentally. Therefore, the model is a tool to predict the effects of
      inhibiting specific metabolic reactions within pancreatic cancer cells, which is
      difficult to measure experimentally, as well as test further hypotheses toward
      targeted therapies.

PMID- 28446881
TI  - Assessment of Airway Distensibility by the Forced Oscillation Technique:
      Reproducible and Potentially Simplifiable.
AB  - A non-invasive index of airway distensibility is required to track airway
      remodeling over time. The forced oscillation technique (FOT) provides such an
      index by measuring the change in respiratory system conductance at 5 Hz over the
      corresponding change in lung volume (DeltaGrs5/DeltaVL). To become useful
      clinically, this method has to be reproducible and easy to perform. The series of
      breathing maneuvers required to measure distensibility would be greatly
      facilitated if the difficulty of breathing below functional residual capacity
      (FRC) could be precluded and the number of maneuvers could be reduced. The
      distensibility at lung volumes below FRC is also reduced by several confounders,
      suggesting that excluding data points below FRC should provide a better surrogate
      for airway remodeling. The objectives of this study were to investigate the
      reproducibility of airway distensibility measured by FOT and to assess whether
      the method could be simplified to increase feasibility. Distensibility was
      measured at three separate occasions in 13 healthy volunteers. At each visit,
      three deflationary maneuvers were performed, each consisting of tidal breathing
      from total lung capacity (TLC) to residual volume by slowly decreasing the end
      expiratory volume on each subsequent breath. Distensibility was calculated by
      using either all data points from TLC to residual volume (RV) or only data points
      from TLC to FRC for either all three or only the first two deflationary
      maneuvers. Intra-class correlation coefficients (ICC) were used to assess
      reproducibility and Bland-Altman analyses were used to assess the level of
      agreement between the differently calculated values of distensibility. The
      results indicate that distensibility calculated using all data points is
      reproducible (ICC = 0.64). Using data points from TLC to FRC slightly improved
      reproducibility (ICC = 0.68) and increased distensibility by 19.4%, which was
      expected as distensibility above FRC should not be affected by confounders. Using
      only data points within the first two maneuvers did not affect reproducibility
      when tested between TLC and FRC (ICC = 0.66). We conclude that a valuable measure
      of airway distensibility could potentially be obtained with only two deflationary
      maneuvers that do not require breathing below FRC. This simplified method would
      increase feasibility without compromising reproducibility.

PMID- 28446880
TI  - Shifts in the Gut Microbiota Composition Due to Depleted Bone Marrow Beta
      Adrenergic Signaling Are Associated with Suppressed Inflammatory Transcriptional
      Networks in the Mouse Colon.
AB  - The brain-gut axis plays a critical role in the regulation of different diseases,
      many of which are characterized by sympathetic dysregulation. However, a direct
      link between sympathetic dysregulation and gut dysbiosis remains to be
      illustrated. Bone marrow (BM)-derived immune cells continuously interact with the
      gut microbiota to maintain homeostasis in the host. Their function is largely
      dependent upon the sympathetic nervous system acting via adrenergic receptors
      present on the BM immune cells. In this study, we utilized a novel chimera mouse
      that lacks the expression of BM beta1/2 adrenergic receptors (b1/2-ARs) to
      investigate the role of the sympathetic drive to the BM in gut and microbiota
      homeostasis. Fecal analyses demonstrated a shift from a dominance of Firmicutes
      to Bacteroidetes phylum in the b1/2-ARs KO chimera, resulting in a reduction in
      Firmicutes/Bacteroidetes ratio. Meanwhile, a significant reduction in
      Proteobacteria phylum was determined. No changes in the abundance of acetate-,
      butyrate-, and lactate-producing bacteria, and colon pathology were observed in
      the b1/2-ARs KO chimera. Transcriptomic profiling in colon identified Killer Cell
      Lectin-Like Receptor Subfamily D, Member 1 (Klrd1), Membrane-Spanning 4-Domains
      Subfamily A Member 4A (Ms4a4b), and Casein Kinase 2 Alpha Prime Polypeptide
      (Csnk2a2) as main transcripts associated with the microbiota shifts in the b1/2
      ARs KO chimera. Suppression of leukocyte-related transcriptome networks (i.e.,
      function, differentiation, migration), classical compliment pathway, and networks
      associated with intestinal function, barrier integrity, and excretion was also
      observed in the colon of the KO chimera. Moreover, reduced expression of
      transcriptional networks related to intestinal diseases (i.e., ileitis,
      enteritis, inflammatory lesions, and stress) was noted. The observed suppressed
      transcriptome networks were associated with a reduction in NK cells, macrophages,
      and CD4+ T cells in the b1/2-ARs KO chimera colon. Thus, sympathetic regulation
      of BM-derived immune cells plays a significant role in modifying inflammatory
      networks in the colon and the gut microbiota composition. To our knowledge, this
      study is the first to suggest a key role of BM b1/2-ARs signaling in host
      microbiota interactions, and reveals specific molecular mechanisms that may lead
      to generation of novel anti-inflammatory treatments for many immune and autonomic
      diseases as well as gut dysbiosis across the board.

PMID- 28446882
TI  - Modified Low-Dose Triiodo-L-thyronine Therapy Safely Improves Function Following
      Myocardial Ischemia-Reperfusion Injury.
AB  - Background: We have shown that thyroid hormones (THs) are cardioprotective and
      can be potentially used as safe therapeutic agents for diabetic cardiomyopathy
      and permanent infarction. However, no reliable, clinically translatable protocol
      exists for TH treatment of myocardial ischemia-reperfusion (IR) injury. We
      hypothesized that modified low-dose triiodo-L-thyronine (T3) therapy would confer
      safe therapeutic benefits against IR injury. Methods: Adult female rats underwent
      left coronary artery ligation for 60 min or sham surgeries. At 2 months following
      surgery and T3 treatment (described below), the rats were subjected to
      functional, morphological, and molecular examination. Results: Following surgery,
      the rats were treated with T3 (8 MUg/kg/day) or vehicle in drinking water ad
      libitum following IR for 2 months. Oral T3 significantly improved left
      ventricular (LV) contractility, relaxation, and relaxation time constant, and
      decreased beta-myosin heavy chain gene expression. As it takes rats ~6 h post
      surgery to begin drinking water, we then investigated whether modified T3 dosing
      initiated immediately upon reperfusion confers additional improvement. We
      injected an intraperitoneal bolus of T3 (12 MUg/kg) upon reperfusion, along with
      low-dose oral T3 (4.5 MUg/kg/day) in drinking water for 2 months. Continuous T3
      therapy (bolus + low-dose oral) enhanced LV contractility compared with oral T3
      alone. Relaxation parameters were also improved compared to vehicle. Importantly,
      these were accomplished without significant increases in hypertrophy, serum free
      T3 levels, or blood pressure. Conclusions: This is the first study to provide a
      safe cardiac therapeutic window and optimized, clinically translatable treatment
      monitoring protocol for myocardial IR using commercially available and
      inexpensive T3. Low-dose oral T3 therapy supplemented with bolus treatment
      initiated upon reperfusion is safer and more efficacious.

PMID- 28446884
TI  - Moods in Clinical Depression Are More Unstable than Severe Normal Sadness.
AB  - OBJECTIVE: Current descriptions in psychiatry and psychology suggest that
      depressed mood in clinical depression is similar to mild sadness experienced in
      everyday life, but more intense and persistent. We evaluated this concept using
      measures of average mood and mood instability (MI). METHOD: We prospectively
      measured low and high moods using separate visual analog scales twice a day for
      seven consecutive days in 137 participants from four published studies.
      Participants were divided into a non-depressed group with a Beck Depression
      Inventory score of <=10 (n = 59) and a depressed group with a Beck Depression
      Inventory score of >=18 (n = 78). MI was determined by the mean square successive
      difference statistic. RESULTS: Mean low and high moods were not correlated in the
      non-depressed group but were strongly positively correlated in the depressed
      group. This difference between correlations was significant. Low MI and high MI
      were weakly positively correlated in the non-depressed group and strongly
      positively correlated in the depressed group. This difference in correlations was
      also significant. CONCLUSION: The results show that low and high moods, and low
      and high MI, are highly correlated in people with depression compared with those
      who are not depressed. Current psychiatric practice does not assess or treat MI
      or brief high mood episodes in patients with depression. New models of mood that
      also focus on MI will need to be developed to address the pattern of mood
      disturbance in people with depression.

PMID- 28446883
TI  - In Vitro and In Vivo Profile of PPL-101 and PPL-103: Mixed Opioid Partial Agonist
      Analgesics with Low Abuse Potential.
AB  - Opiates are still the most effective and widely used treatments for acute and
      chronic pain. However, the problems associated with morphine and other standard
      opioid analgesics severely limit their effectiveness in the clinic. PPL-101 and
      PPL-103 derived from morphine and morphinan ring systems contain a chiral N
      substituent, which confers it with a unique combination of high-binding
      affinities and partial agonist activities at mu, delta, and kappa opioid
      receptors, leading to unique in vivo pharmacology compared to other conventional
      opioids. Acute antinociceptive and reward acquisition of PPL-101 and PPL-103 were
      assessed in mice using the tail flick assay and conditioned place preference
      (CPP) paradigm, respectively. The reinforcing effects of these compounds were
      assessed in rats using the self-administration paradigm. In mice, PPL-101 and PPL
      103 produced antinociception reaching maximal effects that were equivalent to
      morphine at approximately 1/3 and 1/10 of morphine's dose, respectively. PPL-101
      induced antinociception was attenuated following pretreatment with the kappa
      antagonist JDTic, but not the mu opioid antagonist beta-FNA. In mice, PPL-101 and
      PPL-103 produced dose-dependent decreases in activity, similar to other kappa
      agonists; however, they did not produce conditioned place aversion, and in fact
      elicited a trend toward CPP. In rats, neither PPL-101 nor PPL-103 were self
      administered when substituted for morphine and PPL-101 attenuated morphine self
      administration, when administered systemically prior to the self-administration
      session. Collectively, these results indicate that mixed opioid receptor partial
      agonists can produce potent antinociceptive activity with a lack of aversion in
      mice and without being self-administered in rats. Compounds with this profile
      could be superior analgesics with greatly reduced addiction liability and fewer
      side-effects compared to traditional opiates.

PMID- 28446885
TI  - The Impact of Inattention, Hyperactivity/Impulsivity Symptoms, and Executive
      Functions on Learning Behaviors of Children with ADHD.
AB  - Children diagnosed with attention deficit/hyperactivity disorder (ADHD) are at
      risk of experiencing lower academic achievement compared to their peers without
      ADHD. However, we have a limited understanding of the mechanisms underlying this
      association. Both the symptoms of the disorder and the executive functions can
      negatively influence learning behaviors, including motivation, attitude toward
      learning, or persistence, key aspects of the learning process. The first
      objective of this study was to compare different components of learning behaviors
      in children diagnosed with ADHD and typically developing (TD) children. The
      second objective was to analyze the relationships among learning behaviors,
      executive functioning, and symptoms of hyperactivity/impulsivity in both groups.
      Participants were 35 children diagnosed with ADHD and 37 with TD (7-11 years
      old), matched on age and IQ. The teachers filled out the Behavior Rating
      Inventory of Executive Function (BRIEF) and the Learning Behaviors Scale, which
      evaluates Competence/motivation, Attitude toward learning, Attention/persistence,
      and Strategy/flexibility. In addition, parents and teachers filled out the DSM-5
      diagnostic criteria for ADHD. ANOVAs showed significant differences between
      children with ADHD and TD children on all the learning behaviors. Moreover, in
      both the ADHD and TD groups, the behavioral regulation index of the BRIEF
      predicted the search for strategies, and the metacognition index was a good
      predictor of motivation. However, attitude toward learning was predicted by
      metacognition only in the group with ADHD. Therefore, the executive functions had
      greater power than the typical symptoms of inattention and
      hyperactivity/impulsivity in predicting learning behaviors of children with ADHD.
      The findings are in line with other studies that support the influence of the
      executive functions on performance, highlighting the importance of including
      their development as a top priority from early ages in the school setting in
      order to strengthen learning behaviors.

PMID- 28446886
TI  - Parenting and Temperament Influence on School Success in 9-13 Year Olds.
AB  - Children spend a lot of time with their parents who are the first agents that
      educate them. The parenting style implemented in the family influences other
      contexts outside home such as the school. There is evidence that a positive
      parenting style has an influence on school success. However, there are other
      variables related to school success, for example, temperament. The influence of
      parenting decreases with age as children develop abilities to self-regulate
      without parents' external control. The aim of the present study was to evaluate
      the contribution of parenting style and temperament in 9-13 years old children on
      both academic performance and school adjustment skills. Our hypothesis was that
      not only parenting style is crucial to academic performance and school
      adjustment, but also temperament plays an important role in them. We used a
      Parenting Guide line questionnaire to evaluate parenting style, Early Adolescence
      Temperament Questionnaire-R to evaluate temperament; Health Resources Inventory
      to assess children's school adjustment, and academic grades, as indicator of
      academic performance. We were interested in testing whether or not the effect of
      parenting style on academic performance and school adjustment was mediated by
      temperament. We found that emotional and behavioral regulation mediates the
      relation between parenting and academic performance. These findings inform of the
      relevance of child's temperament on school success. Implications for education
      are discussed with emphasis on the importance of understanding students'
      temperament to promote school adjustment and good academic performance.

PMID- 28446887
TI  - The Impact of Prenatal Parental Locus of Control on Children's Psychological
      Outcomes in Infancy and Early Childhood: A Prospective 5 Year Study.
AB  - Locus of control is one of the most widely studied concepts in the history of
      personality psychology. In spite of its popularity and its associations with
      numerous relevant outcomes, the ability of locus of control to predict future
      behaviors involving parenting effectiveness has been under researched. The few
      parent locus of control children's outcome studies are characterized by cross
      sectional methodologies that focus on mothers. The present study uses a
      prospective methodology to compare data on mothers' and fathers' locus of control
      with their child's behavior outcomes from a large scale research project, the
      Avon Longitudinal Study of Parents and Children (ALSPAC). Based on Rotter's
      Social Learning Theory published in 1954 and past empirical research, it was
      predicted and found that parent internality was associated with more positive
      child outcomes than parent externality. More specifically, when both parents were
      internal, their children had more positive outcomes in sleeping, eating, and
      tantrum behavior as compared to any other parent locus of control combination.
      However external parents had a less restrictive attitude which appeared to have a
      more beneficial effect on picky eating. Results confirmed how important parent
      locus of control is in the lives of children. Based on the findings, researchers
      are urged to develop interventions to change advice to parents and promote more
      internal locus of control among parents.

PMID- 28446888
TI  - Money, Food, and Daily Life Objects Are Similarly Shared in the Dictator Game. A
      Study among Poles and Tsimane'.
AB  - The dictator game (DG) is one of the most popular methods for measuring sharing
      behaviors. However, the matter of goods used in the game has rarely been examined
      and discussed. We conducted a study in which all participants played standard
      version of DG in one of the three versions - "money," "food," or "daily life
      objects" sharing. Further, we wanted to expand the generalizability of our
      findings by investigating whether patterns in sharing various goods are
      independent of culture and the level of market integration. Thus, the study was
      conducted among people who function daily under the conditions of low market
      integration (109 Tsimane' - forager-horticulturists from Bolivian Amazon) and in
      a society highly integrated with the market-based economy (85 Polish people). We
      observed that among both Polish and Tsimane' people the participants were equally
      likely to share money, food and small, daily life objects with an unknown
      partner, which implies that generosity might not be related with the type of
      possessed resources. However, regardless of the kind of goods given, Tsimane'
      people were less eager to share with anonymous others than Polish people. We
      present several implications of our findings for studies on generosity and
      altruism.

PMID- 28446889
TI  - The Stroop Color and Word Test.
AB  - The Stroop Color and Word Test (SCWT) is a neuropsychological test extensively
      used to assess the ability to inhibit cognitive interference that occurs when the
      processing of a specific stimulus feature impedes the simultaneous processing of
      a second stimulus attribute, well-known as the Stroop Effect. The aim of the
      present work is to verify the theoretical adequacy of the various scoring methods
      used to measure the Stroop effect. We present a systematic review of studies that
      have provided normative data for the SCWT. We referred to both electronic
      databases (i.e., PubMed, Scopus, Google Scholar) and citations. Our findings show
      that while several scoring methods have been reported in literature, none of the
      reviewed methods enables us to fully assess the Stroop effect. Furthermore, we
      discuss several normative scoring methods from the Italian panorama as reported
      in literature. We claim for an alternative scoring method which takes into
      consideration both speed and accuracy of the response. Finally, we underline the
      importance of assessing the performance in all Stroop Test conditions (word
      reading, color naming, named color-word).

PMID- 28446891
TI  - Moral Attitudes Predict Cheating and Gamesmanship Behaviors Among Competitive
      Tennis Players.
AB  - Background: The present study tested Lee et al.'s (2008) model of moral attitudes
      and cheating behavior in sports in an Italian sample of young tennis players and
      extended it to predict behavior in actual match play. In the first phase of the
      study we proposed that moral, competence and status values would predict
      prosocial and antisocial moral attitudes directly, and indirectly through
      athletes' goal orientations. In the second phase, we hypothesized that moral
      attitudes would directly predict actual cheating behavior observed during match
      play. Method: Adolescent competitive tennis players (N = 314, 76.75% males, M age
      = 14.36 years, SD = 1.50) completed measures of values, goal orientations, and
      moral attitudes. A sub-sample (n = 90) was observed in 45 competitive tennis
      matches by trained observers who recorded their cheating and gamesmanship
      behaviors on a validated checklist. Results: Consistent with hypotheses,
      athletes' values predicted their moral attitudes through the effects of goal
      orientations. Anti-social attitudes directly predicted cheating behavior in
      actual match play providing support for a direct link between moral attitude and
      actual behavior. Conclusion: The present study findings support key propositions
      of Lee and colleagues' model, and extended its application to competitive
      athletes in actual match play.

PMID- 28446890
TI  - Partial Visual Loss Affects Self-reports of Hearing Abilities Measured Using a
      Modified Version of the Speech, Spatial, and Qualities of Hearing Questionnaire.
AB  - We assessed how visually impaired (VI) people perceived their own auditory
      abilities using an established hearing questionnaire, the Speech, Spatial, and
      Qualities of Hearing Scale (SSQ), that was adapted to make it relevant and
      applicable to VI individuals by removing references to visual aspects while
      retaining the meaning of the original questions. The resulting questionnaire, the
      SSQvi, assessed perceived hearing ability in diverse situations including the
      ability to follow conversations with multiple speakers, assessing how far away a
      vehicle is, and the ability to perceptually segregate simultaneous sounds. The
      SSQvi was administered to 33 VI and 33 normally sighted participants. All
      participants had normal hearing or mild hearing loss, and all VI participants had
      some residual visual ability. VI participants gave significantly higher (better)
      scores than sighted participants for: (i) one speech question, indicating less
      difficulty in following a conversation that switches from one person to another,
      (ii) one spatial question, indicating less difficulty in localizing several
      talkers, (iii) three qualities questions, indicating less difficulty with
      segregating speech from music, hearing music more clearly, and better speech
      intelligibility in a car. These findings are consistent with the perceptual
      enhancement hypothesis, that certain auditory abilities are improved to help
      compensate for loss of vision, and show that full visual loss is not necessary
      for perceived changes in auditory ability to occur for a range of auditory
      situations. For all other questions, scores were not significantly different
      between the two groups. Questions related to effort, concentration, and ignoring
      distracting sounds were rated as most difficult for VI participants, as were
      situations involving divided-attention contexts with multiple streams of speech,
      following conversations in noise and in echoic environments, judging elevation or
      distance, and externalizing sounds. The questionnaire has potential clinical
      applications in assessing the success of clinical interventions and setting more
      realistic goals for intervention for those with auditory and/or visual losses.
      The results contribute toward providing benchmark scores for VI individuals.

PMID- 28446892
TI  - The Effect of Coaches' Controlling Style on the Competitive Anxiety of Young
      Athletes.
AB  - Framed on a Self-Determination Theory perspective, the purpose of this study was
      to explore the predictive capacity of coaches' interpersonal controlling style on
      the competitive anxiety of young athletes, considering the mediating effect of
      the athletes' controlled motivation on this relationship. The sample consisted of
      1166 athletes, aged between 9 and 18, who ranked their perceptions of coaches'
      controlling style, as well as the reasons for participating in sport and their
      competitive anxiety before or during competition. The structural models assessing
      both the direct effect of the controlling style on the anxiety and the complete
      mediated effect of the controlled motivation on this relationship revealed good
      fit indices. However, a significant difference of the chi-square was obtained
      when comparing these models to the partial mediation model, providing evidence of
      this last model to be more adequate to describe the relationship between coaches'
      controlling style and athletes' competitive anxiety. Positive significant effects
      of coach controlling style on the three forms of competitive anxiety were found
      (beta CS-SA = 0.21, p < 0.001; beta CS-W = 0.14, p < 0.001; beta CS-CD = 0.30, p
      < 0.001) indicating that coach controlling style could be an antecedent for
      athletes' anxiety in a direct way. Although this style also predicts athletes'
      motivation to participate, this indirect path seems to predict competitive
      anxiety in a less clear way. We discuss our results facing them up to Vallerand's
      hierarchical model postulates, focusing on the relevant influence of coaches on
      the young athletes' experience in the sport context.

PMID- 28446893
TI  - Construction and Validation of the Perceived Opportunity to Craft Scale.
AB  - We developed and validated a scale to measure employees' perceived opportunity to
      craft (POC) in two separate studies conducted in the Netherlands (total N =
      2329). POC is defined as employees' perception of their opportunity to craft
      their job. In Study 1, the perceived opportunity to craft scale (POCS) was
      developed and tested for its factor structure and reliability in an explorative
      way. Study 2 consisted of confirmatory analyses of the factor structure and
      reliability of the scale as well as examination of the discriminant and criterion
      related validity of the POCS. The results indicated that the scale consists of
      one dimension and could be reliably measured with five items. Evidence was found
      for the discriminant validity of the POCS. The scale also showed criterion
      related validity when correlated with job crafting (+), job resources (autonomy
      +; opportunities for professional development +), work engagement (+), and the
      inactive construct cynicism (-). We discuss the implications of these findings
      for theory and practice.

PMID- 28446894
TI  - The Predictive Validity of the Structured Assessment of Violence Risk in Youth
      for Young Spanish Offenders.
AB  - The present study examined the predictive validity of the Structured Assessment
      of Violence Risk in Youth (SAVRY) in a group of young Spanish offenders. The
      sample is made up of 594 minors from the Juvenile Court, between the ages of 14
      and 18 at the time they committed the delinquent act. The SAVRY was able to
      differentiate between low and high-risk younger offenders. Mean scores on risk
      factor are greater in the group of recidivist offenders, the group of non
      recidivist shows higher mean scores in Protective domain. The accuracy of the
      instrument is high (AUCRiskTotalScore = 0.737 and AUCSummaryRiskRating = 0.748).
      An approximation of the predictive validity study of the SAVRY in Spanish younger
      offenders is presented. The results obtained support the SAVRY good functioning
      with not English samples.

PMID- 28446896
TI  - Fixation Patterns of Chinese Participants while Identifying Facial Expressions on
      Chinese Faces.
AB  - Two experiments in this study were designed to explore a model of Chinese
      fixation with four types of native facial expressions-happy, peaceful, sad, and
      angry. In both experiments, participants performed an emotion recognition task
      while their behaviors and eye movements were recorded. Experiment 1 (24
      participants, 12 men) demonstrated that both eye fixations and durations were
      lower for the upper part of the face than for the lower part of the face for all
      four types of facial expression. Experiment 2 (20 participants, 6 men) repeated
      this finding and excluded the disturbance of fixation point. These results
      indicate that Chinese participants demonstrated a superiority effect for the
      lower part of face while interpreting facial expressions, possibly due to the
      influence of eastern etiquette culture.

PMID- 28446895
TI  - All Tapped Out: Touchscreen Interactivity and Young Children's Word Learning.
AB  - Touchscreen devices differ from passive screen media in promoting physical
      interaction with events on the screen. Two studies examined how young children's
      screen-directed actions related to self-regulation (Study 1) and word learning
      (Study 2). In Study 1, 30 2-year-old children's tapping behaviors during game
      play were related to their self-regulation, measured using Carlson's snack task:
      girls and children with high self-regulation tapped significantly less during
      instruction portions of an app (including object labeling events) than did boys
      and children with low self-regulation. Older preschoolers (N = 47, aged 4-6
      years) tapped significantly less during instruction than 2-year-olds did. Study 2
      explored whether the particular way in which 170 children (2-4 years of age)
      interacted with a touchscreen app affected their learning of novel object labels.
      Conditions in which children tapped or dragged a named object to move it across
      the screen required different amounts of effort and focus, compared to a non
      interactive (watching) condition. Age by sex interactions revealed a particular
      benefit of dragging (a motorically challenging behavior) for preschool girls'
      learning compared to that of boys, especially for girls older than age 2. Boys
      benefited more from watching than dragging. Children from low socioeconomic
      status families learned more object names when dragging objects versus tapping
      them, possibly because tapping is a prepotent response that does not require
      thoughtful attention. Parents and industry experts should consider age, sex, self
      regulation, and the physical requirements of children's engagement with
      touchscreens when designing and using educational content.

PMID- 28446897
TI  - Toll-Like Receptor 4-Myeloid Differentiation Primary Response Gene 88 Pathway Is
      Involved in the Inflammatory Development of Polymyositis by Mediating Interferon
      gamma and Interleukin-17A in Humans and Experimental Autoimmune Myositis Mouse
      Model.
AB  - OBJECTIVE: Toll-like receptor 4 (TLR4) is one of the key players in the
      development of many autoimmune diseases. To determine the possible role of TLR4
      in polymyositis (PM) development, we collected muscle samples from PM patients
      and mice subjected to an experimental autoimmune myositis (EAM) model. METHODS:
      We measured TLR4-MyD88 pathway-related factors, interferon-gamma (IFN-gamma), and
      interleukin-17A (IL-17A) in EAM mice and PM patients. Then, we observed the
      changes of above factors and the inflammatory development of EAM mice with TLR4
      antagonist TAK-242, IFN-gamma, or IL-17A antibody treatment. RESULTS: The
      expression of TLR4, MyD88, and NF-kappaB was significantly upregulated in the
      muscle tissues both in 22 patients with PM and in the EAM model. As expected,
      increased levels of various cytokines, such as IL-1beta, IL-6, IL-10, IL-12,
      tumor necrosis factor-alpha, TGF-beta, IFN-gamma, and IL-17A, were evident in the
      serum of EAM mice. Moreover, mRNA expression levels of IFN-gamma and IL-17A were
      significantly increased in both PM patients and EAM mice. Consistently, the
      levels of these factors were positively correlated with the degree of muscle
      inflammation in EAM mice. However, when EAM mice were treated with TLR4
      antagonist TAK-242, the expression of IFN-gamma and IL-17A was decreased. When
      the cytokines were neutralized by anti-IFN-gamma or anti-IL-17A antibody, the
      inflammatory development of EAM exacerbated or mitigated. CONCLUSION: The present
      study provided the important evidence that the TLR4-MyD88 pathway may be involved
      in the immune mechanisms of PM by mediating IFN-gamma and IL-17A.

PMID- 28446898
TI  - Delayed Hospital Presentation and Neuroimaging in Non-surgical Spinal Cord
      Infarction.
AB  - BACKGROUND: Lack of timely recognition and neuroimaging may be a barrier to
      reperfusion efforts in acute spinal cord infarction. METHODS: We performed a
      retrospective study of patients diagnosed with acute non-surgical spinal cord
      infarction at our tertiary academic center from 2001 to 2015. We studied
      parameters associated with time from symptom onset to initial hospital
      presentation and magnetic resonance imaging (MRI) of the spinal cord. RESULTS: We
      identified 39 patients among whom anterior spinal artery syndrome was the most
      frequent presentation (87.2%) and atherosclerosis the most common etiology
      (56.4%). Nearly, half of the patients presented to the emergency department on
      the same day of symptom onset (48.7%) but only nine (23.1%) within the first 6 h.
      Average time from symptom onset to spinal cord MRI was 3.2 days. We could not
      identify clinical, radiological, or outcome patterns associated with early vs.
      delayed presentation and imaging. DISCUSSION: Our study found a time lag from
      symptom onset to hospital presentation and spinal cord MRI in patients with acute
      spinal cord infarction. These findings point at low clinical suspicion of spinal
      cord syndromes and limited recognition as a potentially treatable medical
      emergency.

PMID- 28446899
TI  - Clonal Spread of 16S rRNA Methyltransferase-Producing Klebsiella pneumoniae ST37
      with High Prevalence of ESBLs from Companion Animals in China.
AB  - We screened 30 Klebsiella pneumoniae isolates from dogs and cats at a single
      animal hospital in Guangdong Province, China. Among them, 12 K. pneumoniae
      strains possessed high-level resistance to amikacin and gentamicin and these were
      screened for 16S rRNA methyltransferase (16S-RMTase) genes. And then the genes
      positive isolates were detected for ESBLs (extended spectrum beta-lactamases) and
      analyzed by pulsed-field gel electrophoresis, multilocus sequence typing, PCR
      based replicon typing and plasmid analysis. The genetic profiles of rmtB were
      also determined by PCR mapping. The twelve 16S-RMTase gene-positive isolates were
      rmtB (11/30) and armA (2/30) with one isolate carrying both genes. Extended
      spectrum beta-lactamases genes were represented by blaCTX-M-55 (9/12), blaCTX-M
      27 (2/12) and blaCTX-M-14 (1/12). The twelve 16S-RMTase containing strains were
      grouped into five clonal patterns and ST37 was the most prevalent sequence type.
      Ten rmtB-bearing plasmids conjugated successfully and all belonged to IncN and
      IncF (F33:A-:B-) incompatibility groups. Nine of the transconjugants carried a 97
      kb plasmid and the other harbored both ~60 and ~200 kb plasmids. rmtB and blaCTX
      M-55 were present on the same plasmid and indicated the co-transfer of these two
      genes, with the rmtB gene showing highly relevant relationships with IS26 and
      Tn3. Our findings suggested a high prevalence of 16S-RMTase genes in K. pneumonia
      ST37 from dogs and cats. Additional studies are needed to trace the evolutionary
      path of this type of resistance among the K. pneumonia isolates, and to determine
      whether they have been transferred to humans.

PMID- 28446901
TI  - Anaerobic Methanotrophic Archaea of the ANME-2d Cluster Are Active in a Low
      sulfate, Iron-rich Freshwater Sediment.
AB  - ANaerobic MEthanotrophic (ANME) archaea remove the greenhouse gas methane from
      anoxic environments and diminish its flux to the atmosphere. High methane removal
      efficiencies are well documented in marine environments, whereas anaerobic
      oxidation of methane (AOM) was only recently indicated as an important methane
      sink in freshwater systems. Freshwater AOM-mediating microorganisms lack
      taxonomic identification and only little is known about metabolic adaptions to
      prevailing biogeochemical conditions. One of the first study sites providing
      information about AOM activity in freshwater sediment is Lake Orn, a low-sulfate,
      iron-rich Danish lake. With the aim to identify freshwater AOM-mediating archaea,
      we incubated AOM-active anoxic, nitrate-free freshwater sediment from Lake Orn
      with 13C-labeled methane (13CCH4) and 13C-labeled bicarbonate (13CDIC) and
      followed the assimilation of 13C into RNA by stable isotope probing. While AOM
      was active, 13CCH4 and probably also 13CDIC were incorporated into uncultured
      archaea of the Methanosarcinales-related cluster ANME-2d, whereas other known
      ANME lineages were not detected. This finding strongly suggests that ANME-2d
      archaea perform AOM coupled to sulfate and/or iron reduction and may have the
      capability of mixed assimilation of CH4 and DIC. ANME-2d archaea may thus play an
      important role in controlling methane emissions from nitrate-depleted and low
      sulfate freshwater systems.

PMID- 28446900
TI  - Bioactive Molecule from Streptomyces sp. Mitigates MDR Klebsiella pneumoniae in
      Zebrafish Infection Model.
AB  - The emergence and spread of multi-drug resistant (MDR) especially carbapenem
      resistant Klebsiella pneumoniae is a major emerging threat to public health,
      leading to excess in mortality rate as high as 50-86%. MDR K. pneumoniae
      manifests all broad mechanisms of drug resistance, hence development of new drugs
      to treat MDR K. pneumoniae infection has become a more relevant question in the
      scientific community. In the present study a potential Streptomyces sp. ASK2 was
      isolated from rhizosphere soil of medicinal plant. The multistep HPLC
      purification identified the active principle exhibiting antagonistic activity
      against MDR K. pneumoniae. The purified compound was found to be an aromatic
      compound with aliphatic side chain molecule having a molecular weight of 444.43
      Da. FT-IR showed the presence of OH and C=O as functional groups. The bioactive
      compound was further evaluated for drug induced toxicity and efficacy in adult
      zebrafish infection model. As this is the first study on K. pneumoniae -
      zebrafish model, the infectious doses to manifest sub-clinical and clinical
      infection were optimized. Furthermore, the virulence of K. pneumoniae in
      planktonic and biofilm state was studied in zebrafish. The MTT assay of ex vivo
      culture of zebrafish liver reveals non-toxic nature of the proposed ASK2 compound
      at an effective dose. Moreover, significant increase in survival rate of infected
      zebrafish suggests that ASK2 compound from a new strain of Streptomyces sp. was
      potent in mitigating MDR K. pneumoniae infection.

PMID- 28446902
TI  - Modulation of Macrophage Responses by CMX, a Fusion Protein Composed of Ag85c,
      MPT51, and HspX from Mycobacterium tuberculosis.
AB  - Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is a vaccine used to prevent
      tuberculosis (TB). Due to the poor protection conferred by BCG in adults, new,
      more effective formulations have been developed. A recombinant BCG vaccine
      expressing the CMX fusion protein Ag85c_MPT51_HspX (rBCG-CMX) induced Th1 and
      Th17 responses and provided better protection than BCG. It has been shown that
      Mycobacterium smegmatis expressing CMX also induces better protection than BCG
      and is a strong macrophage activator. The aim of the present study was to
      evaluate macrophage activation by the recombinant CMX fusion protein and by rBCG
      CMX and to evaluate their ability to generate vaccine-specific immune responses.
      The results demonstrate that rCMX protein expressed by BCG (rBCG-CMX) activates
      pulmonary macrophages; increases the expression of activation molecules,
      cytokines, and MHC-II. The interaction with rCMX activates the transcription
      factor NF-kappaB and induces the production of the cytokines TGF-beta, TNF-alpha,
      and IL-6. The in vitro stimulation of bone marrow-derived macrophages (BMMs) from
      TLR-4 or TLR-2 KO mice showed that in the absence of TLR-4, IL-6 was not
      produced. rBCG-CMX was unable to induce CMX-specific Th1 and Th17 cells in TLR-4
      and TLR-2 KO mice, suggesting that these receptors participate in their
      induction. We concluded that both the rBCG-CMX vaccine and the rCMX protein can
      activate macrophages and favor the specific immune response necessary for this
      vaccine.

PMID- 28446903
TI  - Simulating Intestinal Growth Conditions Enhances Toxin Production of
      Enteropathogenic Bacillus cereus.
AB  - Bacillus cereus is a ubiquitous bacterial pathogen increasingly reported to be
      the causative agent of foodborne infections and intoxications. Since the
      enterotoxins linked to the diarrheal form of food poising are foremost produced
      in the human intestine, the toxic potential of enteropathogenic B. cereus strains
      is difficult to predict from studies carried out under routine cultivation
      procedures. In this study, toxigenic properties of a panel of strains (n = 19) of
      diverse origin were compared using cell culture medium pre-incubated with CaCo-2
      cells to mimic intestinal growth conditions. Shortly after contact of the
      bacteria with the simulated host environment, enterotoxin gene expression was
      activated and total protein secretion of all strains was accelerated. Although
      the signal stimulating enterotoxin production still needs to be elucidated, it
      could be shown that it originated from the CaCo-2 cells. Overall, our study
      demonstrates that the currently used methods in B. cereus diagnostics, based on
      standard culture medium, are not allowing a conclusive prediction of the
      potential health risk related to a certain strain. Thus, these methods should be
      complemented by cultivation procedures that are simulating intestinal host
      conditions.

PMID- 28446904
TI  - Dynamic Response of Ammonia-Oxidizers to Four Fertilization Regimes across a
      Wheat-Rice Rotation System.
AB  - Ammonia oxidation by microorganisms is a rate-limiting step of the nitrification
      process and determines the efficiency of fertilizer utilized by crops. Little is
      known about the dynamic response of ammonia-oxidizers to different fertilization
      regimes in a wheat-rice rotation system. Here, we examined ammonia-oxidizing
      bacteria (AOB) and archaea (AOA) communities across eight representative stages
      of wheat and rice growth and under four fertilization regimes: no nitrogen
      fertilization (NNF), chemical fertilization (CF), organic-inorganic mixed
      fertilizer (OIMF) and organic fertilization (OF). The abundance and composition
      of ammonia oxidizers were analyzed using quantitative PCR (qPCR) and terminal
      restriction fragment length polymorphism (T-RFLP) of their amoA genes. Results
      showed that fertilization but not plant growth stages was the best predictor of
      soil AOB community abundance and composition. Soils fertilized with more urea-N
      had higher AOB abundance, while organic-N input showed little effect on AOB
      abundance. 109 bp T-RF (Nitrosospira Cluster 3b) and 280 bp T-RF (Nitrosospira
      Cluster 3c) dominated the AOB communities with opposing responses to
      fertilization regimes. Although the abundance and composition of the AOA
      community was significantly impacted by fertilization and plant growth stage, it
      differed from the AOB community in that there was no particular trend. In
      addition, across the whole wheat-rice rotation stages, results of multiple
      stepwise linear regression revealed that AOB played a more important role in
      ammonia oxidizing process than AOA. This study provided insight into the dynamic
      effects of fertilization strategies on the abundance and composition of ammonia
      oxidizers communities, and also offered insights into the potential of managing
      nitrogen for sustainable agricultural productivity with respect to soil ammonia
      oxidizers.

PMID- 28446905
TI  - Okara: A Nutritionally Valuable By-product Able to Stabilize Lactobacillus
      plantarum during Freeze-drying, Spray-drying, and Storage.
AB  - Okara is a nutritionally valuable by-product produced in large quantities as
      result of soymilk elaboration. This work proposes its use as both culture and
      dehydration medium during freeze-drying, spray-drying, and storage of
      Lactobacillus plantarum CIDCA 83114. Whole and defatted okara were employed as
      culture media for L. plantarum CIDCA 83114. The growth kinetics were followed by
      plate counting and compared with those of bacteria grown in MRS broth (control).
      No significant differences in plate counting were observed in the three media.
      The fatty acid composition of bacteria grown in whole and defatted okara showed a
      noticeable increase in the unsaturated/saturated (U/S) fatty acid ratio, with
      regard to bacteria grown in MRS. This change was mainly due to the increase in
      polyunsaturated fatty acids, namely C18:2. For dehydration assays, cultures in
      the stationary phase were neutralized and freeze-dried (with or without the
      addition of 250 mM sucrose) or spray-dried. Bacteria were plate counted
      immediately after freeze-drying or spray-drying and during storage at 4 degrees C
      for 90 days. Freeze-drying in whole okara conducted to the highest bacterial
      recovery. Regarding storage, spray-dried bacteria previously grown in whole and
      defatted okara showed higher plate counts than those grown in MRS. On the
      contrary, freeze-dried bacteria previously grown in all the three culture media
      were those with the lowest plate counts. The addition of sucrose to the
      dehydration media improved their recovery. The higher recovery of microorganisms
      grown in okara after freeze-drying and spray-drying processes and during storage
      was ascribed to both the presence of fiber and proteins in the dehydration media,
      and the increase in U/S fatty acids ratio in bacterial membranes. The obtained
      results support for the first time the use of okara as an innovative matrix to
      deliver L. plantarum. Considering that okara is an agro-waste obtained in large
      quantities, these results represent an innovative strategy to add it value,
      providing a symbiotic ingredient with promising industrial applications in the
      development of novel functional foods and feeds.

PMID- 28446906
TI  - Stratified Bacterial Diversity along Physico-chemical Gradients in High-Altitude
      Modern Stromatolites.
AB  - At an altitude of 3,570 m, the volcanic lake Socompa in the Argentinean Andes is
      presently the highest site where actively forming stromatolite-like structures
      have been reported. Interestingly, pigment and microsensor analyses performed
      through the different layers of the stromatolites (50 mm-deep) showed steep
      vertical gradients of light and oxygen, hydrogen sulfide and pH in the porewater.
      Given the relatively good characterization of these physico-chemical gradients,
      the aim of this follow-up work was to specifically address how the bacterial
      diversity stratified along the top six layers of the stromatolites which seems
      the most metabolically important and diversified zone of the whole microbial
      community. We herein discussed how, in only 7 mm, a drastic succession of
      metabolic adaptations occurred: i.e., microbial communities shift from a UV
      high/oxic world to an IR-low/anoxic/high H2S environment which force
      stratification and metabolic specialization of the bacterial community, thus,
      modulating the chemical faces of the Socompa stromatolites. The oxic zone was
      dominated by Deinococcus sp. at top surface (0.3 mm), followed by a second layer
      of Coleofasciculus sp. (0.3 to ~2 mm). Sequences from anoxygenic phototrophic
      Alphaproteobacteria, along with an increasing diversity of phyla including
      Bacteroidetes, Spirochaetes were found at middle layers 3 and 4. Deeper layers (5
      7 mm) were mostly occupied by sulfate reducers of Deltaproteobacteria,
      Bacteroidetes and Firmicutes, next to a high diversity and equitable community of
      rare, unclassified and candidate phyla. This analysis showed how microbial
      communities stratified in a physicochemical vertical profile and according to the
      light source. It also gives an insight of which bacterial metabolic capabilities
      might operate and produce a microbial cooperative strategy to thrive in one of
      the most extreme environments on Earth.

PMID- 28446907
TI  - Regulation and Molecular Basis of Environmental Muropeptide Uptake and
      Utilization in Fastidious Oral Anaerobe Tannerella forsythia.
AB  - Tannerella forsythia is a Gram-negative oral anaerobe associated with
      periodontitis. This bacterium is auxotrophic for the peptidoglycan amino sugar N
      acetylmuramic (MurNAc) and likely relies on scavenging peptidoglycan fragments
      (muropeptides) released by cohabiting bacteria during their cell wall recycling.
      Many Gram-negative bacteria utilize an inner membrane permease, AmpG, to
      transport peptidoglycan fragments into their cytoplasm. In the T. forsythia
      genome, the Tanf_08365 ORF has been identified as a homolog of AmpG permease. In
      order to confirm the functionality of Tanf_08365, a reporter system in an
      Escherichia coli host was generated that could detect AmpG-dependent accumulation
      of cytosolic muropeptides via a muropeptide-inducible beta-lactamase reporter
      gene. In trans complementation of this reporter strain with a Tanf_08365
      containing plasmid caused significant induction of beta-lactamase activity
      compared to that with an empty plasmid control. These data indicated that
      Tanf_08365 acted as a functional muropeptide permease causing accumulation of
      muropeptides in E. coli and thus suggested that it is a permease involved in
      muropeptide scavenging in T. forsythia. Furthermore, we showed that the promoter
      regulating the expression of Tanf_08365 was activated significantly by a hybrid
      two-component system regulatory protein, GppX. We also showed that compared to
      the parental T. forsythia strain a mutant lacking GppX in which the expression of
      AmpG was reduced significantly attenuated in utilizing free muropeptides. In
      summary, we have uncovered the mechanism by which this nutritionally fastidious
      microbe accesses released muropeptides in its environment, opening up the
      possibility of targeting this activity to reduce its numbers in periodontitis
      patients with potential benefits in the treatment of disease.

PMID- 28446908
TI  - Association of CTLA-4 Gene Variants with Response to Therapy and Long-term
      Survival in Metastatic Melanoma Patients Treated with Ipilimumab: An Italian
      Melanoma Intergroup Study.
AB  - Ipilimumab (IPI) blocks CTLA-4 immune checkpoint resulting in T cell activation
      and enhanced antitumor immunity. IPI improves overall survival (OS) in 22% of
      patients with metastatic melanoma (MM). We investigated the association of CTLA-4
      single nucleotide variants (SNVs) with best overall response (BOR) to IPI and OS
      in a cohort of 173 MM patients. Patients were genotyped for six CTLA-4 SNVs (
      1661A>G, -1577G>A, -658C>T, -319C>T, +49A>G, and CT60G>A). We assessed the
      association between SNVs and BOR through multinomial logistic regression (MLR)
      and the prognostic effect of SNVs on OS through Kaplan-Meier method. Both 
      1577G>A and CT60G>A SNVs were found significantly associated with BOR. In
      particular, the proportion of responders was higher in G/G genotype while that of
      stable patients was higher in A/A genotype. The frequency of patients
      experiencing progression was similar in all genotypes. MLR evidenced a strong
      downward trend in the probability of responsiveness/progression, in comparison to
      disease stability, as a function of the allele A "dose" (0, 1, or 2) in both SNVs
      with reductions of about 70% (G/A vs G/G) and about 95% (A/A vs G/G). Moreover, 
      1577G/G and CT60G/G genotypes were associated with long-term OS, the surviving
      patients being at 3 years 29.8 and 30.8%, respectively, as compared to 12.9 and
      14.4% of surviving patients carrying -1577G/A and CT60G/A, respectively. MM
      patients carrying -1577G/G or CT60G/G genotypes may benefit from IPI treatment in
      terms of BOR and long-term OS. These CTLA-4 SNVs may serve as potential
      biomarkers predictive of favorable outcome in this subset of patients.

PMID- 28446909
TI  - Clinical Evidence for the Microbiome in Inflammatory Diseases.
AB  - Clinical evidence is accumulating for a role of the microbiome in contributing to
      or modulating severity of inflammatory diseases. These studies can be organized
      by various organ systems involved, as well as type of study approach utilized,
      whether investigators compared the microbiome of cases versus controls, followed
      patients longitudinally, or intervened with antibiotics, prebiotics, or bacterial
      introduction. In this review, we summarize the clinical evidence supporting the
      microbiome as an important mechanism in the onset and maintenance of
      inflammation.

PMID- 28446912
TI  - Temporal and Spatial Variability of Fungal Structures and Host Responses in an
      Incompatible Rust-Wheat Interaction.
AB  - Information about temporal and spatial variability of fungal structures and host
      responses is scarce in comparison to the vast amount of genetic, biochemical, and
      physiological studies of host-pathogen interactions. In this study, we used
      avirulent wild type and virulent mutant isolates of Puccinia striiformis to
      characterize the interactions in wheat carrying yellow rust Yr2 resistance. Both
      conventional and advanced microscopic techniques were used for a detailed study
      of morphology and growth of fungal colonies and associated host cell responses.
      The growth of the wild type isolates was highly restricted due to hypersensitive
      response (HR, plant cell death) indicated by autofluorescence and change in the
      shape of the affected plant cells. The host response appeared post-haustorial,
      but large variation in the time and stage of arrest was observed for individual
      fungal colonies, probably due to a delay between detection and response. Some
      colonies were stopped right after the formation of the primary infection hyphae
      whereas others formed highly branched mycelia. HR was first observed in host
      cells in direct contact with fungal structures, after which the defense responses
      spread to adjacent host cells, and eventually led to encasement of the fungal
      colony. Several cells with HR contained haustoria, which were small and
      underdeveloped, but some cells contained normal sized haustoria without signs of
      hypersensitivity. The growth of the virulent mutants in the resistant plants was
      similar to the growth in plants without Yr2 resistance, which is a strong
      indication that the incompatible phenotype was associated with Yr2. The
      interaction between P. striiformis and wheat with Yr2 resistance was highly
      variable in time and space, which demonstrate that histological studies are
      important for a deeper understanding of host-pathogen interactions and plant
      defense mechanisms in general.

PMID- 28446911
TI  - The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in
      Nosocomial Infections.
AB  - Acinetobacter baumannii is the etiologic agent of a wide range of nosocomial
      infections, including pneumonia, bacteremia, and skin infections. Over the last
      45 years, an alarming increase in the antibiotic resistance of this opportunistic
      microorganism has been reported, a situation that hinders effective treatments.
      In order to develop effective therapies against A. baumannii it is crucial to
      understand the basis of host-bacterium interactions, especially those concerning
      the immune response of the host. Different innate immune cells such as monocytes,
      macrophages, dendritic cells, and natural killer cells have been identified as
      important effectors in the defense against A. baumannii; among them, neutrophils
      represent a key immune cell indispensable for the control of the infection.
      Several immune strategies to combat A. baumannii have been identified such as
      recognition of the bacteria by immune cells through pattern recognition
      receptors, specifically toll-like receptors, which trigger bactericidal
      mechanisms including oxidative burst and cytokine and chemokine production to
      amplify the immune response against the pathogen. However, a complete picture of
      the protective immune strategies activated by this bacteria and its potential
      therapeutic use remains to be determined and explored.

PMID- 28446910
TI  - Are Mast Cells MASTers in Cancer?
AB  - Prolonged low-grade inflammation or smoldering inflammation is a hallmark of
      cancer. Mast cells form a heterogeneous population of immune cells with
      differences in their ultra-structure, morphology, mediator content, and surface
      receptors. Mast cells are widely distributed throughout all tissues and are
      stromal components of the inflammatory microenvironment that modulates tumor
      initiation and development. Although canonically associated with allergic
      disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and
      lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-alpha and IL
      9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and
      Hodgkin's lymphoma) mast cells play a pro-tumorigenic role, in others (e.g.,
      breast cancer) a protective role, whereas in yet others they are apparently
      innocent bystanders. These seemingly conflicting results suggest that the role of
      mast cells and their mediators could be cancer specific. The microlocalization
      (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in
      the initiation/progression of solid and hematologic tumors. Increasing evidence
      in certain experimental models indicates that targeting mast cells and/or their
      mediators represent a potential therapeutic target in cancer. Thus, mast cells
      deserve focused consideration also as therapeutic targets in different types of
      tumors. There are many unanswered questions that should be addressed before we
      understand whether mast cells are an ally, adversary, or innocent bystanders in
      human cancers.

PMID- 28446913
TI  - De novo Transcriptome Analysis of Miscanthus lutarioriparius Identifies Candidate
      Genes in Rhizome Development.
AB  - HIGHLIGHTDe novo transcriptome profiling of five tissues reveals candidate genes
      putatively involved in rhizome development in M. lutarioriparius. Miscanthus
      lutarioriparius is a promising lignocellulosic feedstock for second-generation
      bioethanol production. However, the genomic resource for this species is
      relatively limited thus hampers our understanding of the molecular mechanisms
      underlying many important biological processes. In this study, we performed the
      first de novo transcriptome analysis of five tissues (leaf, stem, root, lateral
      bud and rhizome bud) of M. lutarioriparius with an emphasis to identify putative
      genes involved in rhizome development. Approximately 66 gigabase (GB) paired-end
      clean reads were obtained and assembled into 169,064 unigenes with an average
      length of 759 bp. Among these unigenes, 103,899 (61.5%) were annotated in seven
      public protein databases. Differential gene expression profiling analysis
      revealed that 4,609, 3,188, 1,679, 1,218, and 1,077 genes were predominantly
      expressed in root, leaf, stem, lateral bud, and rhizome bud, respectively. Their
      expression patterns were further classified into 12 distinct clusters. Pathway
      enrichment analysis revealed that genes predominantly expressed in rhizome bud
      were mainly involved in primary metabolism and hormone signaling and transduction
      pathways. Noteworthy, 19 transcription factors (TFs) and 16 hormone signaling
      pathway-related genes were identified to be predominantly expressed in rhizome
      bud compared with the other tissues, suggesting putative roles in rhizome
      formation and development. In addition, a predictive regulatory network was
      constructed between four TFs and six auxin and abscisic acid (ABA) -related
      genes. Furthermore, the expression of 24 rhizome-specific genes was further
      validated by quantitative real-time RT-PCR (qRT-PCR) analysis. Taken together,
      this study provide a global portrait of gene expression across five different
      tissues and reveal preliminary insights into rhizome growth and development. The
      data presented will contribute to our understanding of the molecular mechanisms
      underlying rhizome development in M. lutarioriparius and remarkably enrich the
      genomic resources of Miscanthus.

PMID- 28446914
TI  - Constructing Integrated Networks for Identifying New Secondary Metabolic Pathway
      Regulators in Grapevine: Recent Applications and Future Opportunities.
AB  - Representing large biological data as networks is becoming increasingly adopted
      for predicting gene function while elucidating the multifaceted organization of
      life processes. In grapevine (Vitis vinifera L.), network analyses have been
      mostly adopted to contribute to the understanding of the regulatory mechanisms
      that control berry composition. Whereas, some studies have used gene co
      expression networks to find common pathways and putative targets for
      transcription factors related to development and metabolism, others have defined
      networks of primary and secondary metabolites for characterizing the main
      metabolic differences between cultivars throughout fruit ripening. Lately,
      proteomic-related networks and those integrating genome-wide analyses of promoter
      regulatory elements have also been generated. The integration of all these data
      in multilayered networks allows building complex maps of molecular regulation and
      interaction. This perspective article describes the currently available network
      data and related resources for grapevine. With the aim of illustrating data
      integration approaches into network construction and analysis in grapevine, we
      searched for berry-specific regulators of the phenylpropanoid pathway. We
      generated a composite network consisting of overlaying maps of co-expression
      between structural and transcription factor genes, integrated with the presence
      of promoter cis-binding elements, microRNAs, and long non-coding RNAs (lncRNA).
      This approach revealed new uncharacterized transcription factors together with
      several microRNAs potentially regulating different steps of the phenylpropanoid
      pathway, and one particular lncRNA compromising the expression of nine stilbene
      synthase (STS) genes located in chromosome 10. Application of network-based
      approaches into multi-omics data will continue providing supplementary resources
      to address important questions regarding grapevine fruit quality and composition.

PMID- 28446915
TI  - Pruning System and Foliar Application of MgSO 4 Alter Yield and Secondary
      Metabolite Profile of Rosa damascena under Rainfed Acidic Conditions.
AB  - Damask rose (Rosa damascena Mill.) is one of the most high-value essential oil
      bearing plants in the world. However, the flower yield and quality of essential
      oil of R. damascena are largely influenced by the pruning practices and balanced
      supply of plant nutrition. The objective of this study was to test the hypothesis
      whether the pruning system and foliar fertilization of MgSO4 would influence the
      flower yield, growth and secondary metabolites profile of R. damascena. A field
      experiment of 10 treatment combinations comprising two pruning systems (complete
      and partial) and five levels of MgSO4 (water spray, MgSO4 @ 5.0g L-1, 10.0g L
      1,15.0g L-1, and 20.0g L-1) was conducted. The experiment was conducted in
      randomized block design with factorial arrangement. Overall, the flower yield
      ranged from 503.66 to 1114.47 g bush-1, while oil content varied from 0.039 to
      0.046% of the fresh flower. Irrespective of foliar spray, partial pruning
      produced significantly (P <= 0.05) higher flower yield (893.02 and 503.66 g bush
      1) compared with complete pruning system in both the years. Regardless of pruning
      system, the foliar application of MgSO4 @ 15.0g L-1 registered about 26-38%
      higher flower yield compared with water spray control. The major constituents of
      essential oil were citronellol (19.75-48.88%), E-geraniol (9.63-29.6%), Z-citral
      (0.07-5.97%), nonadecane (6.76-22.32%), and heneicosane (2.87-10.21%). The
      principal component analysis revealed that the major hydrocarbons such as
      nonadecene, nonadecane, and heptadecane are positively and highly correlated with
      each others. The results suggest that higher yield and quality of R. damascena
      can be achieved through partial pruning system in combination with foliar
      application MgSO4 under rainfed acidic conditions.

PMID- 28446916
TI  - Oil Accumulation in Transgenic Potato Tubers Alters Starch Quality and
      Nutritional Profile.
AB  - Plant storage compounds such as starch and lipids are important for human and
      animal nutrition as well as industry. There is interest in diverting some of the
      carbon stored in starch-rich organs (leaves, tubers, and cereal grains) into
      lipids in order to improve the energy density or nutritional properties of crops
      as well as providing new sources of feedstocks for food and manufacturing.
      Previously, we generated transgenic potato plants that accumulate up to 3.3%
      triacylglycerol (TAG) by dry weight in the tubers, which also led to changes in
      starch content, starch granule morphology and soluble sugar content. The aim of
      this study was to investigate how TAG accumulation affects the nutritional and
      processing properties of high oil potatoes with a particular focus on starch
      structure, physical and chemical properties. Overall, TAG accumulation was
      correlated with increased energy density, total nitrogen, amino acids, organic
      acids and inorganic phosphate, which could be of potential nutritional benefit.
      However, TAG accumulation had negative effects on starch quality as well as
      quantity. Starch from high oil potatoes had lower amylose and phosphate content,
      reduced peak viscosity and higher gelatinization temperature. Interestingly,
      starch pasting properties were disproportionately affected in lines accumulating
      the highest levels of TAG (>2.5%) compared to those accumulating only moderate
      levels (0.2-1.6%). These results indicate that optimized engineering of
      specialized crops for food, feed, fuel and chemical industries requires careful
      selection of traits, and an appropriate level of transgene expression, as well as
      a better understanding of starch structure and carbon partitioning in plant
      storage organs.

PMID- 28446917
TI  - Shoot the Message, Not the Messenger-Combating Pathogenic Virulence in Plants by
      Inhibiting Quorum Sensing Mediated Signaling Molecules.
AB  - Immunity, virulence, biofilm formation, and survival in the host environment are
      regulated by the versatile nature of density dependent microbial cell signaling,
      also called quorum sensing (QS). The QS molecules can associate with host plant
      tissues and, at times, cause a change in its gene expression at the downstream
      level through inter-kingdom cross talking. Progress in controlling QS through
      fungicide/bactericide in pathogenic microscopic organisms has lead to a rise of
      antibiotic resistance pathogens. Here, we review the application of selective
      quorum quenching (QQ) endophytes to control phytopathogens that are shared by
      most, if not all, terrestrial plant species as well as aquatic plants. Allowing
      the plants to posses endophytic colonies through biotization will be an
      additional and a sustainable encompassing methodology resulting in attenuated
      virulence rather than killing the pathogens. Furthermore, the introduced
      endophytes could serve as a potential biofertilizer and bioprotection agent,
      which in turn increases the PAMP- triggered immunity and hormonal systemic
      acquired resistance (SAR) in plants through SA-JA-ET signaling systems. This
      paper discusses major challenges imposed by QS and QQ application in
      biotechnology.

PMID- 28446919
TI  - High Nitrogen Supply Induces Physiological Responsiveness to Long Photoperiod in
      Barley.
AB  - Photoperiod and nutrient nitrogen (N) supply influence the growth, development,
      and productivity of crops. This study examined the physiological, biochemical,
      and morpho-anatomical traits of NA5 and NA9, two barley cultivars with
      contrasting photoperiod lengths, under the combined treatment of photoperiod
      regime and N supply. Under long photoperiod, high N supply decreased net
      photosynthesis; decreased chlorophyll a and chlorophyll a/b; decreased ascorbate
      peroxidase (APX), catalase (CAT), and superoxide dismutase (SOD) activities;
      decreased ascorbate, glutathione, soluble protein, and soluble sugar; destroyed
      mesophyll cell integrity; and increased [Formula: see text], malondialdehyde, and
      proline in both NA5 and NA9. Under short photoperiod, high N content increased
      net photosynthesis; increased chlorophyll a and chlorophyll a/b; increased APX,
      CAT, and SOD activities; and increased antioxidants, soluble protein, and soluble
      sugar in NA9 but decreased the same parameters in NA5. These results indicated
      that N supply strongly affected photosynthetic capacity and the balance of
      reactive oxygen species in response to short and long photoperiod. High N supply
      enhanced the sensitivity of long-day barley to photoperiod change by inhibiting
      photosynthesis and decreasing antioxidant defense ability. High N mitigated the
      undesirable effects of shortened photoperiod in short-day barley. Therefore, the
      data from this study revealed that N status affects adaptation to photoperiod
      changes by maintaining redox homeostasis and photosynthetic capacity.

PMID- 28446920
TI  - Two Highly Similar Poplar Paleo-subgenomes Suggest an Autotetraploid Ancestor of
      Salicaceae Plants.
AB  - As a model plant to study perennial trees in the Salicaceae family, the poplar
      (Populus trichocarpa) genome was sequenced, revealing recurrent paleo
      polyploidizations during its evolution. A comparative and hierarchical alignment
      of its genome to a well-selected reference genome would help us better understand
      poplar's genome structure and gene family evolution. Here, by adopting the
      relatively simpler grape (Vitis vinifera) genome as reference, and by inferring
      both intra- and inter-genomic gene collinearity, we produced a united alignment
      of these two genomes and hierarchically distinguished the layers of paralogous
      and orthologous genes, as related to recursive polyploidizations and speciation.
      We uncovered homologous blocks in the grape and poplar genomes and also between
      them. Moreover, we characterized the genes missing and found that poplar had two
      considerably similar subgenomes (<=0.05 difference in gene deletion) produced by
      the Salicaceae-common tetraploidization, suggesting its autotetraploid nature.
      Taken together, this work provides a timely and valuable dataset of orthologous
      and paralogous genes for further study of the genome structure and functional
      evolution of poplar and other Salicaceae plants.

PMID- 28446918
TI  - MicroRNA and Transcription Factor: Key Players in Plant Regulatory Network.
AB  - Recent achievements in plant microRNA (miRNA), a large class of small and non
      coding RNAs, are very exciting. A wide array of techniques involving forward
      genetic, molecular cloning, bioinformatic analysis, and the latest technology,
      deep sequencing have greatly advanced miRNA discovery. A tiny miRNA sequence has
      the ability to target single/multiple mRNA targets. Most of the miRNA targets are
      transcription factors (TFs) which have paramount importance in regulating the
      plant growth and development. Various families of TFs, which have regulated a
      range of regulatory networks, may assist plants to grow under normal and stress
      environmental conditions. This present review focuses on the regulatory
      relationships between miRNAs and different families of TFs like; NF-Y, MYB, AP2,
      TCP, WRKY, NAC, GRF, and SPL. For instance NF-Y play important role during
      drought tolerance and flower development, MYB are involved in signal transduction
      and biosynthesis of secondary metabolites, AP2 regulate the floral development
      and nodule formation, TCP direct leaf development and growth hormones signaling.
      WRKY have known roles in multiple stress tolerances, NAC regulate lateral root
      formation, GRF are involved in root growth, flower, and seed development, and SPL
      regulate plant transition from juvenile to adult. We also studied the relation
      between miRNAs and TFs by consolidating the research findings from different
      plant species which will help plant scientists in understanding the mechanism of
      action and interaction between these regulators in the plant growth and
      development under normal and stress environmental conditions.

PMID- 28446921
TI  - Roles of Nuclear Pores and Nucleo-cytoplasmic Trafficking in Plant Stress
      Responses.
AB  - The nuclear pore complex (NPC) is a large protein complex that controls the
      exchange of components between the nucleus and the cytoplasm. In plants, the NPC
      family components play critical roles not only in essential growth and
      developmental processes, but also in plant responses to various environmental
      stress conditions. The involvement of NPC components in plant stress responses is
      mainly attributed to different mechanisms including control of mRNA/protein
      nucleo-cytoplasmic trafficking and transcriptional gene regulation. This mini
      review summarizes current knowledge of the NPC-mediated plant stress responses
      and provides an overview of the underlying molecular mechanisms.

PMID- 28446922
TI  - Corrigendum: Building a Genetic Manipulation Tool Box for Orchid Biology:
      Identification of Constitutive Promoters and Application of CRISPR/Cas9 in the
      Orchid, Dendrobium officinale.
AB  - [This corrects the article on p. 2036 in vol. 7, PMID: 28127299.].

PMID- 28446924
TI  - Differential Leukocyte Counting via Fluorescent Detection and Image Processing on
      a Centrifugal Microfluidic Platform.
AB  - Centrifugal microfluidics has received much attention in the last decade for the
      automation of blood testing at the point-of-care, specifically for the detection
      of chemistries, proteins, and nucleic acids. However, the detection of common
      blood cells on-disc, particularly leukocytes, remains a challenge. In this paper,
      we present two analytical methods for enumerating leukocytes on a centrifugal
      platform using a custom-built fluorescent microscope, acridine orange nuclear
      staining, and image processing techniques. In the first method, cell analysis is
      performed in glass capillary tubes; in the second, acrylic chips are used. A bulk
      cell analysis approach is implemented in both cases where the pixel areas of
      fractionated lymphocyte/monocyte and granulocyte layers are correlated with cell
      counts. Generating standard curves using porcine blood sample controls, we
      observed strong linear fits to measured cell counts using both methods. Analyzing
      the pixel intensities of the fluorescing white cell region, we are able to
      differentiate lymphocytes from monocytes via pixel clustering, demonstrating the
      capacity to perform a 3-part differential. Finally, a discussion of pros and cons
      of the bulk-cell analysis approach concludes the paper.

PMID- 28446925
TI  - Ethical, legal and clinical aspects of live surgery in urology - contemporary
      issues and a glimpse of the future.
AB  - Beside dry and wet lab training, simulators, video tapes, fellowships and
      clinical visits, live surgery has gained popularity during the last years, being
      an attraction point at large scientific meetings and at postgraduate courses as
      well. This type of surgical training raises both ethical and legal issues. Thus,
      there are professional societies that have banned such meetings, mainly due to
      safety reasons for the patient. The current article aims to identify and to
      discuss ethical and legal issues related to the topic, advantages, disadvantages
      and weak points of this emerging challenge for modern medicine, trying to analyze
      the issues from all relevant points of view: those of the patient, the surgeon
      and the session attendant.

PMID- 28446926
TI  - Are we ready for the ERAS protocol in colorectal surgery?
AB  - INTRODUCTION: Modern perioperative care principles in elective colorectal surgery
      have already been established by international surgical authorities.
      Nevertheless, barriers to the introduction of routine evidence-based clinical
      care and changing dogmas still exist. One of the factors is the surgeon. AIM: To
      assess perioperative care trends in elective colorectal surgery among general
      surgery consultants in surgical departments in Malopolska Voivodeship, Poland.
      MATERIAL AND METHODS: An anonymous standardized 20-question questionnaire was
      developed based on ERAS principles and sent out to Malopolska Voivodeship general
      surgery departments. Answers of general surgery consultants showed the level of
      acceptance of elements of perioperative care. RESULTS: The overall response rate
      was 66%. Several elements (antibiotic and antithrombotic prophylaxis,
      postoperative oxygen therapy, no nasogastric tubes) had quite a high acceptance
      rate. On the other hand, most crucial surgical perioperative elements (lack of
      mechanical bowel preparation, preoperative oral carbohydrate loading, use of
      laparoscopy and lack of drains, early fluid and oral diet intake, early
      mobilization) were not followed according to evidence-based ERAS protocol
      recommendations. Surgeons were not willing to change their practice, but were
      supportive of changes in anesthesiologist-dependent elements of perioperative
      care, such as restrictive fluid therapy, use of transversus abdominis plane
      blocks, etc. CONCLUSIONS: Many elements of perioperative care in elective
      colorectal surgery in Malopolska Voivodeship are still dictated by dogma and are
      not evidence-based. The level of acceptance of many important ERAS protocol
      elements is low. Surgeons are ready to accept only changes that do not interfere
      with their practice.

PMID- 28446923
TI  - Sensory nerve regeneration after epithelium wounding in normal and diabetic
      cornea.
AB  - The cornea is the most densely innervated mammalian tissue. The sensory nerves
      are responsible for sensations of dryness, temperature, touch, and pain, and play
      important roles in the blink reflex, wound healing, and tear production. Many
      ocular and systemic diseases can adversely affect corneal sensory nerve and
      consequently impair their function. One of such systemic diseases is diabetes
      mellitus (DM) which causes sensory degeneration, neurotrophic keratopathy (DNK),
      and delayed wound healing. In this review, we summarize recent discoveries
      revealing mechanisms underlying the pathogenesis of DNK and the impairment of
      sensory nerve regeneration in post wound diabetic corneas in using animal model
      of human diabetes. Because it is generally believed that common mechanisms are
      operative in the pathogenesis of diabetic peripheral neuropathy in different
      tissues, the findings in the corneas have implications in in other tissues such
      as the skin, which often leads to foot ulceration and amputation in diabetic
      patients.

PMID- 28446927
TI  - The experience and awareness of laparoendoscopic procedures among Polish surgeons
      in everyday clinical practice.
AB  - INTRODUCTION: In 2012, a total of 56 647 inguinal hernia repairs were performed
      in Poland. However, the absence of a uniform hernia repair register obscures the
      current herniology status in Poland, especially regarding laparoendoscopic
      procedures. AIM: To determine the awareness of laparoendoscopic procedures among
      Polish surgeons and to ascertain their everyday clinical practice. MATERIAL AND
      METHODS: The data were collected at the national hernia conference in 2016,
      during an interactive session for surgeons with a special interest in herniology.
      They could respond to the survey items using the VoxVote application. All items
      and response options were displayed on participants' smartphones. The questions
      were related to transabdominal preperitoneal/totally extraperitoneal (TAPP/TEP)
      hernia repair. The surgeons responded to 27 questions regarding routine inguinal
      hernia repair. One hundred and six surgeons from all regions of Poland
      participated in the survey. RESULTS: 19.2% of respondents never inform patients
      about the possibility of performing laparoendoscopic repair. 45.2% admitted that
      they had referred a patient with a difficult inguinal hernia to another hospital
      or surgeon. Seventy-five percent stated they would be willing to perform TAPP/TEP
      if the reimbursement rates were more favourable. In bilateral hernias, 61.6% of
      the respondents perform a two-step open repair, while only 25% perform a single
      stage laparoendoscopic repair of bilateral hernia. In women, only 13.3% perform
      laparoendoscopic hernia repairs, and 19.0% do not use mesh. CONCLUSIONS: The
      skill level to perform TAPP/TEP repair is still inadequate among Polish surgeons.
      The absence of accurate data makes it impossible to verify whether the treatment
      methods used are compliant with the guidelines.

PMID- 28446928
TI  - Thromboelastographic changes during laparoscopic fundoplication.
AB  - INTRODUCTION: Thromboelastography (TEG) is a technique that measures coagulation
      processes and surveys the properties of a viscoelastic blood clot, from its
      formation to lysis. AIM: To determine the possible hypercoagulability state and
      the effect of antithrombotic prophylaxis on thromboelastogram results and
      development of venous thrombosis during laparoscopic fundoplication. MATERIAL AND
      METHODS: The study was performed on 106 patients who were randomized into two
      groups. The first group received low-molecular-weight heparin (LMWH) 12 h before
      the operation, and 6 and 30 h after it. The second group received LMWH only 1 h
      before the laparoscopic fundoplication. The TEG profile was collected before LMWH
      injection, 1 h after the introduction of the laparoscope and 15 min after the
      surgery was completed. RESULTS: There was no significant difference in
      thromboelastography R-time between the groups before low-molecular-weight heparin
      injection. In group I preoperative R-values significantly decreased 1 h after the
      introduction of the laparoscope, after the end of surgery and on the third
      postoperative day. K-time values decreased significantly on the third
      postoperative day compared with the results before low-molecular-weight heparin
      injection, and after the operation. In group II, preoperative R-values
      significantly decreased 1 h after the introduction of the laparoscope, and after
      surgery. K-time values did not change significantly during or after the
      laparoscopic operation. CONCLUSIONS: Our study results demonstrated that the
      hypercoagulation state (according to the TEG results) was observed during and
      after laparoscopic fundoplication in patients when LMWH was administered 12 h
      before the operation together with intraoperative intermittent pneumatic
      compression. The optimal anticoagulation was obtained when LMWH was administered
      1 h before fundoplication.

PMID- 28446929
TI  - Comparison of Harmonic scalpel and Ligasure devices in laparoscopic Roux-en-Y
      gastric bypass.
AB  - INTRODUCTION: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most
      preferred bariatric procedures in the world for surgical treatment of morbid
      obesity. The Harmonic scalpel (HS) and LigaSure (LS) are the most commonly used
      devices in laparoscopic surgery. As far as we know, there is no comparative study
      of the two energy devices in LRYGB for morbid obesity. AIM: To compare the
      intraoperative performances of the two energy devices in LRYGB for morbid
      obesity. MATERIAL AND METHODS: The HS and LS were used in 43 and 42 cases,
      respectively. The patient demographics of both groups were comparable. The
      duration of the procedures (gastric pouch creation time and total operation
      time), quantity of bleeding (during gastric pouch creation and total quantities
      of bleeding) and the number of pneumoperitoneum desufflations due to smoking that
      impaired sight fields were recorded prospectively. RESULTS: Gastric pouch
      creation time (HS: 22.5 +/-9.5 vs. LS: 19.5 +/-9.7 min, p = 0.15), bleeding
      during gastric pouch preparation (HS: 15.3 +/-30.5 vs. LS: 17.5 +/-31.3 ml, p =
      0.74), total operation time (HS: 183.2 +/-47 vs. LS: 165.3 +/-37.1 min, p = 0.06)
      and total bleeding (HS: 110 +/-195.5 vs. LS: 102.5 +/-70 ml, p = 0.81) were
      similar in the two groups. Only the mean number of pneumoperitoneum desufflations
      due to smoking was lower in the HS group (HS: 0.28 +/-0.49 vs. LS: 0.57 +/-0.78,
      p = 0.04). CONCLUSIONS: The HS and LS performed similarly in LRYGB, with fewer
      desufflations from smoking in the HS group.

PMID- 28446930
TI  - Revisional bariatric surgery after failed laparoscopic adjustable gastric banding
      - a single-center, long-term retrospective study.
AB  - INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) used to be one of
      the most popular bariatric procedures. AIM: To present our institution's
      experience with LAGB, its complications, causes of failure and revisional
      bariatric procedures, in a long-term follow-up. MATERIAL AND METHODS: Records of
      patients who underwent pars flaccida LAGB from 2003 to 2006 were gathered. We
      selected data on patients with a history of additional bariatric procedures.
      Their initial demographic data, body mass index and causes of revision were
      gathered. We analyzed length of stay and early perioperative complications.
      RESULTS: 60% of patients (n = 57) who underwent LAGB in our institution between
      2003 and 2006 had their band removed (out of 107, 11% lost to follow-up). Median
      time to revisional surgery was 50 months. The main reasons for removal were:
      weight regain (n = 23; 40%), band slippage (n = 14; 25%), and pouch dilatation (n
      = 9; 16%). Thirty (53%) patients required additional bariatric surgery, 10 (33%)
      of which were simultaneous with band removal. The most popular procedures were:
      laparoscopic Roux-en-Y gastric bypass (LRYGB) (n = 15; 50%), open gastric bypass
      (n = 8; 27%), and laparoscopic sleeve gastrectomy (LSG) - (n = 3; 10%). Mean
      length of stay (LOS) was 5.4 +/-2.0. One (3%) perioperative complication was
      reported. CONCLUSIONS: The results show that LAGB is not an effective bariatric
      procedure in long-term follow-up due to the high rate of complications causing
      band removal and the high rate of obesity recurrence. Revisional bariatric
      surgery after failed LAGB may be performed in a one-stage approach with band
      removal.

PMID- 28446931
TI  - Evaluation of the results of treatment of morbid obesity by the endoscopic
      intragastric balloon implantation method.
AB  - INTRODUCTION: Overweight and obesity are ranked in the fifth place among the risk
      factors responsible for the greatest number of deaths in the world. AIM: To
      assess the effects of treatment of patients with morbid obesity using endoscopic
      intragastric balloon (IGB) implantation. MATERIAL AND METHODS: Two hundred and
      seventy-two patients with obesity were treated using endoscopic intragastric
      balloon implantation. Upon analysis of the inclusion and exclusion criteria, the
      study covered a group of 63 patients with morbid obesity. The patients were
      implanted with the LexBal balloon. Reduction of excess body mass, changes to BMI
      values and ailments and complications divided into mild and severe were assessed.
      RESULTS: Before intragastric balloon treatment, the average body mass index (BMI)
      value was 58.3 +/-10.5 kg/m2, whereas after 6 months of treatment it decreased to
      49.5 +/-8.7 kg/m2. The patients with postoperative BMI equal to or greater than
      50.0 kg/m2 reported nausea (69.7%), vomiting (51.5%), flatulence (45.5%), upper
      abdominal pain (36.4%) and general discomfort (424%) more frequently. Dehydration
      (9.1%) was also more frequent in this group, whereas frequency of occurrence of
      such ailments and complications as heartburn (23.3%) and oesophageal candidiasis
      (10.0%) was higher in the patients with postoperative BMI below 50.0 kg/m2.
      CONCLUSIONS: Endoscopic intragastric balloon implantation is an effective and
      safe method of excess body mass reduction in patients with morbid obesity before
      a planned bariatric surgical procedure. Pre-operative excess body mass and BMI
      value and post-operative excess weight loss in patients with morbid obesity have
      no impact on frequency of occurrence of ailments and complications in IGB
      treatment.

PMID- 28446932
TI  - Telemedical assessment of the level of energy expenditure in overweight and obese
      individuals.
AB  - INTRODUCTION: Increasing the energy expenditure above the elementary level of
      metabolism by undertaking regular physical activity causes body mass reduction
      and its maintenance at a healthy level. AIM: To remote assessment of the level of
      physical activity in a group of overweight and obese individuals. MATERIAL AND
      METHODS: The research was conducted in the Department of Rehabilitation at the
      Institute of Rural Health, Lublin, Poland, and included a group of 514 volunteers
      of both genders (38 +/-12 years). The examined group was divided into three
      subgroups depending on the body mass index (BMI) level (I - normal, II -
      overweight, III - obese). The level of physical activity at home was assessed
      based of the short version of the International Physical Activity Questionnaire
      (IPAQ), conducted by means of a mobile application, and was compared with data
      registered by the accelerometer of a smartphone. RESULTS: The IPAQ-assessed level
      of the physical activity expressed in MET-min/week amounted to the following
      values: group I: 5190.38 +/-6629.84, group II: 5099.53 +/-6380.97, group III:
      3939.31 +/-4000.73; and the caloric cost (cal * week-1) amounted to: group I:
      5825.47 +/-7512.99, group II: 7204.09 +/-9187.96), and group III: 7002.10 +/
      7296.22. Registered levels of physical activity (MET-min/week) were lower than
      IPAQ-assessed: in group I (3741.24 +/-3958.29), in group II (2447.72 +/-2156.44)
      and in group III (1927.42 +/-1790.85) (p < 0.05). CONCLUSIONS: The average values
      of energy expenditure showed a declining tendency, together with an increase in
      the BMI. On the other hand, the total weekly caloric cost showed the lowest
      average values in the group with normal body mass.

PMID- 28446933
TI  - Stress as a factor contributing to obesity in patients qualified for bariatric
      surgery - studies in a selected group of patients (a pilot study).
AB  - INTRODUCTION: Recently, the incidence of obesity, especially extreme obesity, has
      significantly increased. It is connected with inappropriate lifestyle, including
      a high calorie diet, psychological and genetic factors, some medications,
      diseases or infectious factors. Nowadays, the consumption of food is not only to
      satisfy a physiological need, but also fulfils psychological needs. The most
      effective method of morbid obesity treatment is metabolic surgery. Moreover, food
      is considered to be a reward and method of coping with stress. In order to
      improve the efficiency of the surgical treatment, it seems significant to assess
      the effects of psychological factors on eating behaviours. AIM: To evaluate the
      effects of stress on eating habits that increase the risk of extreme obesity.
      MATERIAL AND METHODS: The study included 50 subjects qualified for bariatric
      surgery. The authors' own questionnaire and standardised PSS-10 questionnaire by
      Cohen, Kamarcki and Mermelstein adapted by Juczynski and Oginska-Bulik were used.
      RESULTS: These questionnaires indicated that patients felt a moderate levels of
      stress but with a tendency for high levels. The majority of respondents declared
      an increased appetite due to stress-causing factors. Reasons for snacking most
      frequently included negative emotions and feeling like eating something.
      Consumption of additional snacks was a way of coping with stress. Most frequently
      the subjects ate sweets and salty snacks, but also sandwiches, nuts, fruit and
      alcohol beverages. CONCLUSIONS: Psychological support may help morbidly obese
      people both to change nutritional habits and to cope with stress.

PMID- 28446934
TI  - Endoscopic extraperitoneal radical prostatectomy after radical resection of pT1
      pT2 rectal cancer: a report of thirty cases.
AB  - INTRODUCTION: Endoscopic extraperitoneal radical prostatectomy (EERPE) has gained
      popularity for the treatment of localized prostate cancer. However, prior complex
      lower abdominal or pelvic surgery can complicate subsequent EERPE. To date, there
      have been few reports on patients who underwent EERPE after radical resection of
      pT1-pT2 rectal cancer. AIM: To present our experience with EERPE in patients
      after radical resection of pT1-pT2 rectal carcinoma and introduce a simple and
      effective way to create an extraperitoneal working space. MATERIAL AND METHODS:
      Thirty patients after radical resection of pT1-pT2 rectal carcinoma were treated
      with EERPE for biopsy-proven localized prostate cancer. Operation time, estimated
      blood loss, conversion to open surgery rate, transfusion rate and transurethral
      catheter time were recorded. Meanwhile, functional outcome (continence and
      potency) and oncological outcome were reviewed. RESULTS: The average operative
      time was 168 min. Mean blood loss was 195 ml. There was no need for conversion to
      open surgery or transfusion. The catheter was removed on postoperative day (POD)
      7.8. After a mean follow-up time of 53.1 months, 3 patients had a prostate
      specific antigen level relapse over 0.1 ng/ml. At the follow-up time, 26 patients
      were completely continent, and 4 needed 1-2 pads/day. Of the 6 patients who
      underwent neurovascular bundle preservation, none have experienced return of
      erections at the last follow-up time. CONCLUSIONS: Endoscopic extraperitoneal
      radical prostatectomy after radical resection of rectal carcinoma appears
      promising, with feasibility in experienced hands. The operative data,
      postoperative urinary incontinence and oncological outcomes appear encouraging,
      but the rate of erectile dysfunction seems to be disappointing.

PMID- 28446935
TI  - Anaesthesia of the posterior urethra and pain reduction during cystoscopy - a
      randomized controlled trial.
AB  - INTRODUCTION: Standard intra-urethral instillation of anaesthetic gel may not
      sufficiently exclude pain perception during cystoscopy. AIM: To evaluate the
      impact of the anaesthesia within the posterior urethra on pain intensity related
      to cystoscopy in men. MATERIAL AND METHODS: One hundred and twenty-seven men
      undergoing cystoscopy were prospectively enrolled in the study. Patients were
      randomly assigned to the experimental or control group (66 vs. 61 patients).
      Intra-urethral instillation of 2% lidocaine gel was done in both groups. In the
      experimental group, the posterior urethra was additionally anaesthetized with
      distribution of the lidocaine gel by catheterisation. The study endpoints were
      pain intensity at successive time points of the procedure assessed on a numeric
      rating scale, overall pain intensity assessed on a Likert scale, the need for
      analgesics during 6 h after the procedure, and the frequency of urinary tract
      infections (UTIs) during 14 days after the procedure. RESULTS: Pain perception
      during cystoscopy did not differ significantly between the two groups (p > 0.05).
      However, after 6 h patients in the experimental group were more likely to declare
      that the cystoscopy was painless (81.8% vs. 70.2%, relative risk = 1.17). The
      need for analgesics and the incidence of UTI were similar in both groups (p >
      0.05). Statistically significant differences regarding pain perception were
      observed depending on patients' age and the number of transurethral procedures
      performed in the past, with no relation to type of anaesthesia (p < 0.05).
      CONCLUSIONS: Anaesthesia of the posterior urethra is not more efficacious in
      reducing pain related to cystoscopy than standard instillation of anaesthetic
      gel. However, it improves the general perception of the procedure, and hence may
      positively influence patients' compliance.

PMID- 28446936
TI  - Predictors of postoperative hemoglobin drop after laparoscopic myomectomy.
AB  - INTRODUCTION: Laparoscopic myomectomy (LM) can be associated with significant
      bleeding. AIM: To identify factors influencing the postoperative hemoglobin (Hb)
      drop after LM. MATERIAL AND METHODS: This is a retrospective, single-center
      study. We evaluated data of 150 consecutive patients undergoing LM due to
      intramural myomas between 2010 and 2015. RESULTS: The median age of the patients
      was 37 (23-53) years. The mean diameter of the largest myoma was 5.7 +/-2.3 (1.5
      12) cm. The mean surgical time was 83 +/-38 (35-299) min. The median number of
      sutures was 3 (1-11). The mean postoperative Hb drop was 1.6 +/-1.2 (0-6) g/dl,
      and the mean estimated blood loss was 261 +/-159 (50-1700) ml. In the univariate
      analysis, the postoperative Hb drop correlated with the duration of surgery (p <
      0.001), diameter of the largest myoma (p < 0.001), cumulative myoma weight (p <
      0.001), and number of sutures (p < 0.001), but not with patients' age or number
      of intramural myomas. In the multivariable analysis, the surgical time (beta =
      0.395, p < 0.001), diameter of the largest myoma (beta = 0.292, p = 0.03) and
      preoperative Hb concentration (beta = 0.299, p < 0.001) predicted the
      postoperative Hb change. CONCLUSIONS: Surgical time and dominant myoma diameter
      are independent predictors of the postoperative Hb drop after LM.

PMID- 28446937
TI  - Laparoscopic isthmocele treatment - single center experience.
AB  - INTRODUCTION: A cesarean section is the most frequently performed surgery in
      modern obstetrics. In case of an incorrect wound healing process there is a risk
      of a persistent uterine wall defect. Nowadays, due to the high frequency of
      cesarean sections, obstetricians have to deal with the threat of uterine rupture
      due to pathological wound healing. It has been proven that isthmocele can cause
      abnormal uterine bleeding (AUB), pelvic pain (PP), and secondary infertility
      (SI), and can be a place of improper pregnancy placement. AIM: This article
      presents our experience with isthmocele treatment. We describe our diagnostic
      process scheme, method of corrective surgery and main therapeutic outcomes.
      MATERIAL AND METHODS: In this manuscript we present a single center's experience
      in isthmocele therapy. We have operated on 16 patients who suffered from abnormal
      uterine bleeding, pain disorders or secondary infertility possibly due to a
      cesarean scar defect. RESULTS: The results obtained in our center are promising.
      In 9 of 11 (81.8%) women with abnormal bleeding we obtained complete resolution
      of symptoms. We had slightly worse results in the case of pelvic pain. In 4
      (66.6%) of 6 patients the pain resolved completely. We have obtained 7
      pregnancies in 11 (63.6%) patients operated on due to secondary infertility.
      CONCLUSIONS: In our opinion, laparoscopic treatment seems to be currently one of
      the most effective methods in isthmocele therapy. Further investigation is
      necessary to determine the indications for surgery, suitable treatment strategies
      and appropriate care.

PMID- 28446938
TI  - Minimally invasive surgery for resection of ossification of the ligamentum flavum
      in the thoracic spine.
AB  - INTRODUCTION: Thoracic ossification of the ligamentum flavum (TOLF) is a common
      cause of progressive thoracic myelopathy. Surgical decompression is commonly used
      to treat TOLF. AIM: To evaluate the clinical outcomes of microsurgical
      decompression of TOLF via a paraspinal approach, using a percutaneous tubular
      retractor system. MATERIAL AND METHODS: First, three-dimensional (3D) image
      reconstruction and printed models were made from thin computed tomography scans
      for each patient. Then, 3D computer-assisted virtual surgery was performed using
      the 3D reconstruction to calculate the precise location and sizes of the bone
      window and the angle of insertion of the percutaneous tubular retractor system.
      In total, 13 patients underwent the surgery through the percutaneous micro
      channel unilateral vertebral approach under electrophysiological monitoring. Five
      days after the surgery, increased creatine phosphokinase levels returned to
      preoperative levels. The Japanese Orthopedic Association (JOA) score was improved
      and computed tomography reconstruction and magnetic resonance imaging of the
      thoracic spine showed that decompression was achieved without injuries to the
      spinal cord or nerve root. The stability of the spine was not affected, nor were
      any deformities of the spine detected. Finally, nerve functional recovery was
      achieved with minimal injury to the paraspinal muscle, articulum, spinous process
      and ligament. RESULTS: The mean operative time was 98.23 +/-19.10 min, and mean
      blood loss was 19.77 +/-5.97 ml. At a mean follow-up of 13.3 months (median: 12
      months), the mean JOA score was 7.54 +/-1.13 at the final follow-up, yielding a
      mean RR of 49.10 +/-15.71%. Using The recovery rate, 7 (53.85%) patients had good
      outcomes, 5 (38.46%) patients had a fair outcome, and 1 (7.69%) patient had poor
      outcomes, indicating significant improvement by the final follow-up examination
      (p < 0.05). CONCLUSIONS: The 3D printed patient model-based microsurgical
      resection of TOLF via the paraspinal approach can achieve decompression of the
      spinal canal with minimal complications, faster recovery and improved stability
      of the vertebral body.

PMID- 28446939
TI  - Management of uterine artery pseudoaneurysm: advanced ultrasonography imaging and
      laparoscopic surgery as an alternative method to angio-computed tomography and
      transarterial embolization.
AB  - Uterine artery pseudoaneurysms (UAP) are rare but potentially life-threatening
      lesions. They may occur after traumatic deliveries, cesarean sections, and other
      interventions. We present a case of a 39-year-old woman with a UAP. The patient
      was accurately diagnosed using ultrasound imaging, with subsequent diagnostic
      hysteroscopy and laparoscopic excision of the UAP. In the present case, a
      ligation of the artery branch was performed to provide accurate hemostasis during
      UAP dissection. The vascular lesion was partially enucleated and removed,
      followed by recreation of the previous uterine shape. Power Doppler with HD flow
      and 3D ultrasound are accurate methods in the diagnosis of UAP. We are of the
      opinion that laparoscopic surgery can be on a par with transarterial
      embolization. During laparoscopy, the surgeon can either close the feeding vessel
      or remove the pathological tissue. In our opinion, this method solves the problem
      permanently and, after a successful case series with long-term follow-up, might
      be applied in other centers as well.

PMID- 28446940
TI  - A case of disseminated peritoneal leiomyomatosis after two laparoscopic
      procedures due to uterine fibroids.
AB  - Disseminated peritoneal leiomyomatosis (DPL) is a rare disorder characterized by
      the presence of multifocal nodules and tumors composed of proliferating smooth
      muscle tissue, spread throughout the peritoneum. Estrogens and progesterone are
      considered to be the main factors initiating the formation of disseminated
      leiomyomatosis. Disseminated peritoneal leiomyomatosis is often asymptomatic, and
      acyclic vaginal bleeding or pain in the lower abdomen is associated with
      leiomyomatous rebuilt uterus corpus. Disseminated peritoneal leiomyomatosis can
      have other ambiguous presentation. The difficulty in DPL diagnosis is that it is
      not always accompanied by scattered leiomyomas and can occur after menopause.
      Some cases of DPL are associated with surgical procedures on uterine fibroids,
      especially with the use of a morcellator. We present the case of a 39-year-old
      woman with DPL who underwent laparoscopic myomectomy and laparoscopic
      supracervical hysterectomy before the final diagnosis of DPL. After the complete
      surgical treatment performed in our center the patient is free of symptoms.

PMID- 28446941
TI  - Use and Communication of Probabilistic Forecasts.
AB  - Probabilistic forecasts are becoming more and more available. How should they be
      used and communicated? What are the obstacles to their use in practice? I review
      experience with five problems where probabilistic forecasting played an important
      role. This leads me to identify five types of potential users: Low Stakes Users,
      who don't need probabilistic forecasts; General Assessors, who need an overall
      idea of the uncertainty in the forecast; Change Assessors, who need to know if a
      change is out of line with expectatations; Risk Avoiders, who wish to limit the
      risk of an adverse outcome; and Decision Theorists, who quantify their loss
      function and perform the decision-theoretic calculations. This suggests that it
      is important to interact with users and to consider their goals. The cognitive
      research tells us that calibration is important for trust in probability
      forecasts, and that it is important to match the verbal expression with the task.
      The cognitive load should be minimized, reducing the probabilistic forecast to a
      single percentile if appropriate. Probabilities of adverse events and percentiles
      of the predictive distribution of quantities of interest seem often to be the
      best way to summarize probabilistic forecasts. Formal decision theory has an
      important role, but in a limited range of applications.

PMID- 28446942
TI  - Cardiac CT Improves Outcomes in Stable Coronary Heart Disease: Results of Recent
      Clinical Trials.
AB  - PURPOSE OF REVIEW: The purpose of this study was to review the recent randomised
      controlled trials of coronary computed tomography angiography (CCTA) for patients
      with stable coronary artery disease. RECENT FINDINGS: The initial results and
      subsequent papers from the SCOT-HEART (Scottish COmputed Tomography of the HEART)
      and PROMISE (PROspective Multicentre Imaging Study for Evaluation of chest pain)
      trials have shown that CCTA is a safe and appropriate addition to standard care
      or alternative to functional testing. The SCOT-HEART study showed that CCTA
      changes diagnoses, improves diagnostic certainty, changes management, leads to
      more appropriate use of invasive coronary angiography, and reduces fatal and non
      fatal myocardial infarction. A meta-analysis of the four randomised controlled
      trials showed that CCTA leads to a major reduction in myocardial infarction in
      patients with stable chest pain. SUMMARY: CCTA is now an established technique
      for the assessment of coronary artery disease. Recent 'test and treat' randomised
      controlled trials have shown that CCTA guided changes in management can improve
      clinical outcomes.

PMID- 28446944
TI  - Protective Effects of Proline-Rich Peptide in a Rat Model of Alzheimer Disease:
      An Electrophysiological Study.
AB  - INTRODUCTION: Alzheimer disease (AD) is the most common form of dementia in the
      elderly that slowly destroys memory and cognitive functions. The disease has no
      cure and leads to significant structural and functional brain abnormalities. To
      facilitate the treatment of this disease, we aimed to investigate proline-rich
      peptide (PRP-1) action of hypothalamus on hippocampal (HP) neurons and dynamics
      of their recovery, after intracerebroventricular (ICV) injection of amyloid-beta
      (Abeta). METHODS: Experiments were carried out on 24 adult, male Albino rats
      (average weight: 230+/-30 g). The animals were randomly divided into 3 groups
      (control, Abeta, and Abeta plus PRP-1). Electrophysiological patterns of
      hippocampal neurons in response to stimulation of entorhinal cortex (EC) with
      high frequency stimulation (50 Hz) were studied. RESULTS: It was found that Abeta
      (25-35) suppresses the electrical activity of hippocampal neurons. The PRP-1
      would return this activity to normal levels. CONCLUSION: In general, PRP-1 has
      protective effect against AD-related alterations induced by amyloid peptides.
      This protective effect is probably due to stimulation of the immune and glia
      system.

PMID- 28446943
TI  - The Updated NICE Guidelines: Cardiac CT as the First-Line Test for Coronary
      Artery Disease.
AB  - PURPOSE OF REVIEW: Cost-effective care pathways are integral to delivering
      sustainable healthcare programmes. Due to the overestimation of coronary artery
      disease using traditional risk tables, non-invasive testing has been utilised to
      improve risk stratification and initiate appropriate management to reduce the
      dependence on invasive investigations. In line with recent technological
      improvements, cardiac CT is a modality that offers a detailed anatomical
      assessment of coronary artery disease comparable to invasive coronary
      angiography. RECENT FINDINGS: The recent publication of the National Institute
      for Health and Care Excellences (NICE) Clinical Guideline 95 update assesses the
      performance and cost utility of different non-invasive imaging strategies in
      patients presenting with suspected anginal chest pain. The low cost and high
      sensitivity of cardiac CT makes it the non-invasive test of choice in the
      evaluation of stable angina. This has now been ratified in national guidelines
      with NICE recommending cardiac CT as the first-line investigation for all
      patients presenting with chest pain due to suspected coronary artery disease.
      Additionally, randomised controlled trials have demonstrated that cardiac CT
      improves diagnostic certainty when incorporated into chest pain pathways.
      SUMMARY: NICE recommend cardiac CT as the first-line test for the evaluation of
      stable coronary artery disease in chest pain pathways.

PMID- 28446945
TI  - Diffusion Tensor Imaging for Glioma Grading: Analysis of Fiber Density Index.
AB  - INTRODUCTION: The most common primary tumors of brain are gliomas and tumor
      grading is essential for designing proper treatment strategies. The gold standard
      choice to determine grade of glial tumor is biopsy which is an invasive method.
      The purpose of this study was to investigate the role of fiber density index
      (FDi) by means of diffusion tensor imaging (DTI) (as a noninvasive method) in
      glial tumor grading. METHODS: A group of 20 patients with histologically
      confirmed diagnosis of gliomas were evaluated in this study. We used a 1.5 Tesla
      MR system (AVANTO; Siemens, Germany) with a standard head coil for scanning.
      Multidirectional diffusion weighted imaging (measured in 12 noncollinear
      directions), and T1 weighted nonenhanced were performed for all patients. We
      defined two regions of interest (ROIs); 1) White matter fibers near the tumor and
      2) Similar fibers in the contralateral hemisphere. RESULTS: FDi of the low-grade
      gliomas was higher than those of high-grade gliomas, which was significant
      (P=0.017). FDi ratio (ratio of fiber density in vicinity of the tumor to
      homologous fiber tracts in the contralateral hemisphere) is higher in low-grade
      than high-grade tumors, (P=0.05). In addition, we performed ROC (receiver
      operating characteristic) curve and the area under curve (AUC) was
      0.813(P=0.013). CONCLUSION: Our findings prove significant difference in FDi near
      by low-grade and high-grade gliomas. Therefore, FDi values and ratios are helpful
      in glial tumor grading.

PMID- 28446946
TI  - Neural Imaging Using Single-Photon Avalanche Diodes.
AB  - INTRODUCTION: This paper analyses the ability of single-photon avalanche diodes
      (SPADs) for neural imaging. The current trend in the production of SPADs moves
      toward the minimum dark count rate (DCR) and maximum photon detection probability
      (PDP). Moreover, the jitter response which is the main measurement characteristic
      for the timing uncertainty is progressing. METHODS: The neural imaging process
      using SPADs can be performed by means of florescence lifetime imaging (FLIM),
      time correlated single-photon counting (TCSPC), positron emission tomography
      (PET), and single-photon emission computed tomography (SPECT). RESULTS: This
      trend will result in more precise neural imaging cameras. While achieving low DCR
      SPADs is difficult in deep submicron technologies because of using higher doping
      profiles, higher PDPs are reported in green and blue part of light. Furthermore,
      the number of pixels integrated in the same chip is increasing with the
      technology progress which can result in the higher resolution of imaging.
      CONCLUSION: This study proposes implemented SPADs in Deep-submicron technologies
      to be used in neural imaging cameras, due to the small size pixels and higher
      timing accuracies.

PMID- 28446947
TI  - Event-Related Potentials of Bottom-Up and Top-Down Processing of Emotional Faces.
AB  - INTRODUCTION: Emotional stimulus is processed automatically in a bottom-up way or
      can be processed voluntarily in a top-down way. Imaging studies have indicated
      that bottom-up and top-down processing are mediated through different neural
      systems. However, temporal differentiation of top-down versus bottom-up
      processing of facial emotional expressions has remained to be clarified. The
      present study aimed to explore the time course of these processes as indexed by
      the emotion-specific P100 and late positive potential (LPP) event-related
      potential (ERP) components in a group of healthy women. METHODS: Fourteen female
      students of Alzahra University, Tehran, Iran aged 18-30 years, voluntarily
      participated in the study. The subjects completed 2 overt and covert emotional
      tasks during ERP acquisition. RESULTS: The results indicated that fearful
      expressions significantly produced greater P100 amplitude compared to other
      expressions. Moreover, the P100 findings showed an interaction between emotion
      and processing conditions. Further analysis indicated that within the overt
      condition, fearful expressions elicited more P100 amplitude compared to other
      emotional expressions. Also, overt conditions created significantly more LPP
      latencies and amplitudes compared to covert conditions. CONCLUSION: Based on the
      results, early perceptual processing of fearful face expressions is enhanced in
      top-down way compared to bottom-up way. It also suggests that P100 may reflect an
      attentional bias toward fearful emotions. However, no such differentiation was
      observed within later processing stages of face expressions, as indexed by the
      ERP LPP component, in a top-down versus bottom-up way. Overall, this study
      provides a basis for further exploring of bottom-up and top-down processes
      underlying emotion and may be typically helpful for investigating the temporal
      characteristics associated with impaired emotional processing in psychiatric
      disorders.

PMID- 28446948
TI  - Characterization of Nociceptive Behaviors Induced by Formalin in the Glabrous and
      Hairy Skin of Rats.
AB  - INTRODUCTION: Glabrous skin and hairy skin are innervated by different types of
      noxious fibers. However, the different nociceptive behaviors induced by formalin,
      a commonly used model of acute inflammatory pain, have not yet been
      systematically examined in the glabrous and hairy skin. METHODS: In this study,
      we compared nociceptive behaviors induced by formalin injections (2%, 4%, and 8%)
      into either glabrous skin (plantar surface) of the hind paw or hairy skin of the
      hind limb in adult rats. RESULTS: A typical biphasic nociceptive response was
      seen after formalin injection into the plantar surface of the hind paw. A brief
      interphase separates the first and second phases where nociceptive behaviors were
      barely spotted. However, following subcutaneous injection into the hairy skin
      nociceptive behaviors were only seen after 10 minutes of formalin injection,
      which correlates in time with the second phase of the formalin response. First
      phase nociceptive behaviors were never seen with hairy skin injection, even
      following multiple injections of formalin. CONCLUSION: These data suggest that
      nociceptive behaviors and spinal responses induced by formalin injections to
      glabrous and hairy skin areas are different, and that the first and second phases
      may be mediated through different noxious afferent fibers.

PMID- 28446949
TI  - Reliability of Motor Evoked Potentials Induced by Transcranial Magnetic
      Stimulation: The Effects of Initial Motor Evoked Potentials Removal.
AB  - INTRODUCTION: Transcranial magnetic stimulation (TMS) is a useful tool for
      assessment of corticospinal excitability (CSE) changes in both healthy
      individuals and patients with brain disorders. The usefulness of TMS-elicited
      motor evoked potentials (MEPs) for the assessment of CSE in a clinical context
      depends on their intra-and inter-session reliability. This study aimed to
      evaluate if removal of initial MEPs elicited by using two types of TMS techniques
      influences the reliability scores and whether this effect is different in blocks
      with variable number of MEPs. METHODS: Twenty-three healthy participants were
      recruited in this study. The stimulus intensity was set at 120% of resting motor
      threshold (RMT) for one group while the stimulus intensity was adjusted to record
      MEPs up to 1 mV for the other group. Twenty MEPs were recorded at 3 time points
      on 2 separate days. An intra-class correlation coefficient (ICC) reliability with
      absolute agreement and analysis of variance model were used to assess reliability
      of the MEP amplitudes for blocks with variable number of MEPs. RESULTS: A
      decrease in ICC values was observed with removal of 3 or 5 MEPs in both
      techniques when compared to all MEP responses in any given block. Therefore,
      removal of the first 3 or 5 MEPs failed to further increase the reliability of
      MEP responses. CONCLUSION: Our findings revealed that a greater number of trials
      involving averaged MEPs can influence TMS reliability more than removal of the
      first trials.

PMID- 28446950
TI  - Analgesic Effect of 17beta-Estradiol on Nucleus Paragigantocellularis Lateralis
      of Male Rats Mediated Via GABAA Receptors.
AB  - INTRODUCTION: Beside its autonomic functions, the nucleus paragigantocellularis
      lateralis (LPGi) is involved in the descending pain modulation. 17beta-Estradiol
      is a neuroactive steroid found in several brain areas such as LPGi. Intra-LPGi
      microinjection of 17beta-estradiol can elicit the analgesic responses. 17beta
      Estradiol modulates nociception by binding to estrogenic receptors as well as
      allosteric interaction with other membrane-bound receptors like GABAA receptors.
      This study aimed to examine the role of GABAA receptors in the pain modulating
      effect of intra-LPGi injection of 17beta-estradiol. METHODS: To study the
      antinociceptive effects of 17beta-estradiol, cannulation into the LPGi nucleus of
      male Wistar rats was performed. About 500 nL of drug was administered 15 minutes
      prior to formalin injection (50 MUL of 4%). Then, formalin-induced flexing and
      licking behaviors were recorded for 60 minutes. For evaluating the role of GABAA
      receptors in the estradiol-induced pain modulation, 17beta-estradiol was
      administered into the LPGi nucleus 15 minutes after the injection of 25 ng/MUL
      bicuculline (the GABAA receptor antagonist). Then, the formalin-induced responses
      were recorded. RESULTS: The results of the current study showed that intra-LPGi
      injection of 17beta-estradiol decreased the flexing duration in both phases of
      formalin test (P<0.001); but it only attenuated the second phase of licking
      behavior (P<0.001). 17beta-estradiol attenuated the second phase of formalin test
      of both behaviors (P<0.001). Bicuculline prevented the antinociceptive effect of
      intra-LPGi 17beta-estradiol in both first and second phases of formalin-induced
      responses (P<0.001). CONCLUSION: According to the results of this study, the
      analgesic effect of intra-LPGi 17beta-estradiol on the formalin-induced
      inflammatory pain might be mediated via GABAA receptors.

PMID- 28446951
TI  - Power Spectral Density Analysis of Purkinje Cell Tonic and Burst Firing Patterns
      From a Rat Model of Ataxia and Riluzole Treated.
AB  - INTRODUCTION: Purkinje Cell (PC) output displays a complex firing pattern
      consisting of high frequency sodium spikes and low frequency calcium spikes, and
      disruption in this firing behavior may contribute to cerebellar ataxia. Riluzole,
      neuroprotective agent, has been demonstrated to have neuroprotective effects in
      cerebellar ataxia. Here, the spectral analysis of PCs firing in control, 3
      acetylpyridine (3-AP), neurotoxin agent, treated alone and riluzole plus 3-AP
      treated were investigated to determine changes in the firing properties.
      Difference in the power spectra of tonic and burst firing was assessed.
      Furthermore, the role of calcium-activated potassium channels in the power
      spectra was evaluated. METHODS: Analysis was performed using Matlab. Power
      spectral density (PSD) of PCs output were obtained. Peak frequencies were
      extracted from the spectrum and statistical comparisons were done. In addition, a
      multi-compartment computational model of a Purkinje cell was used. This
      computational stimulation allowed us to study the changes in the power spectral
      density of the PC output as a result of alteration in ion channels. RESULTS:
      Spectral analysis showed that in the spectrum of tonic and burst firing pattern
      only high sodium frequency and low calcium frequency was seen, respectively. In
      addition, there was a significant difference between the frequency components of
      PCs firing obtained from normal, ataxia and riluzole treated rats. Results
      indicated that sodium firing frequency of normal, ataxic and treated PCs occurred
      in approximate frequency of 22.53+/-5.49, 6.46+/-0.23, and 31.34+/-4.07 Hz,
      respectively; and calcium frequency occurred in frequency of 4.22+/-2.02, 1.52+/
      1.19, and 3.88+/-1.37 Hz, respectively. The simulation results demonstrated that
      blockade of calcium-activated potassium channels in the PC model changed the PSD
      of the PC model firing activity. This change was similar to PSD changes in ataxia
      condition. CONCLUSION: These alterations in the spectrum of PC output may be a
      basis for developing possible new treatment strategies to improve cerebellar
      ataxia.

PMID- 28446952
TI  - The Effect of Group-Based Occupational Therapy on Performance and Satisfaction of
      Stroke Survivors: Pilot Trail, Neuro-Occupational View.
AB  - INTRODUCTION: Stroke imposes limitations on performing activities of daily living
      (ADL) and their level. Different therapeutic approaches are used for improving
      the level of performance after a stroke. This study was performed with the aim of
      evaluating the effect of group-based occupational therapy on improving the
      performance of ADL and satisfaction of its performance in patients with chronic
      strokes. METHODS: Fourteen chronic stroke patients with the mean age of 52 years
      participated in the study. The participants were assigned into two groups
      (control and treatment). The level of performance of ADL, level of stroke
      disability, and participation were respectively evaluated by Barthel index (BI),
      modified Rankin scale (MRS), and Canadian Occupational Performance Measure
      (COPM). Six sessions of group therapy tasks were scheduled with an emphasis on
      three main activities, including mobility exercises, craft, and cooking. RESULTS:
      The COPM changes in the 'performance' and 'satisfaction' scores in the treatment
      group and the 'performance' scores in the control group were significant. The MRS
      scale in the two groups revealed no change in the level of stroke disability.
      However, the changes in the ADL performance in BI were significant. CONCLUSION:
      The current study indicated that doing daily, craft, and mobility activities in
      the groups can affect the 'performance' and 'satisfaction' levels in stroke
      patients.

PMID- 28446953
TI  - Neuroprotective Effects of Exercise on Brain Edema and Neurological Movement
      Disorders Following the Cerebral Ischemia and Reperfusion in Rats.
AB  - INTRODUCTION: Cerebral ischemia and reperfusion causes physiological and
      biochemical changes in the neuronal cells that will eventually lead to cell
      damage. Evidence indicates that exercise reduces the ischemia and reperfusion
      induced brain damages in animal models of stroke. In the present study, the
      effect of exercise preconditioning on brain edema and neurological movement
      disorders following the cerebral ischemia and reperfusion in rats was
      investigated. METHODS: Twenty-one adult male wistar rats (weighing 260-300 g)
      were randomly divided into three groups: sham operated, exercise plus ischemia,
      and ischemia group (7 rats per group). The rats in exercise group were trained to
      run on a treadmill 5 days a week for 4 weeks. Transient focal cerebral ischemia
      and reperfusion were induced by middle cerebral artery occlusion (MCAO) for 60
      minutes, followed by reperfusion for 23 hours. After 24 hours ischemia, movement
      disorders were tested by a special neurological examination. Also, cerebral edema
      was assessed by determining the brain water content. RESULTS: The results showed
      that pre-ischemic exercise significantly reduced brain edema (P<0.05). In
      addition, exercise preconditioning decreased the neurological movement disorders
      caused by brain ischemia and reperfusion (P<0.05). CONCLUSION: Preconditioning by
      exercise had neuroprotective effects against brain ischemia and reperfusion
      induced edema and movement disorders. Thus, it could be considered as a useful
      strategy for prevention of ischemic injuries, especially in people at risk.

PMID- 28446954
TI  - Comment on the Effect of Endocannabinoid System on Rat Behavior.

PMID- 28446955
TI  - Combination of Cyclamen persicum Mill. floral gene promoters and chimeric
      repressors for the modification of ornamental traits in Torenia fournieri Lind.
AB  - Although chimeric repressors such as the Arabidopsis TCP3 repressor are known to
      have significant effects on flower morphology and color, their cellular-level
      effects on flower petals are not understood. The promoter sequences of the genes
      expressed in the flowers of cyclamen, a representative potted flower grown during
      the winter season, are also unknown. Here, we isolated eight promoters from
      cyclamen genes that are reportedly expressed in the petals. These promoters were
      then fused to four chimeric repressors and introduced into the model flower
      torenia to screen for effective combinations of promoters and repressors for
      flower breeding. As expected, some of the constructs altered flower phenotypes
      upon transformation. We further analyzed the effects of chimeric repressors at
      the cellular level. We observed that complicated petal and leaf serrations were
      accompanied by excessive vascular branching. Dichromatism in purple anthocyanin
      was inferred to result in bluish flowers, and imbalanced cell proliferation
      appeared to result in epinastic flowers. Thus, the genetic constructs and
      phenotypic changes described in this report will benefit the future breeding and
      characterization of ornamental flowers.

PMID- 28446956
TI  - A novel PEX1 mutation in a Moroccan family with Zellweger spectrum disorders.
AB  - Mutations in the PEX1 gene are usually associated with recessive inherited
      diseases including Zellweger spectrum disorders. In this work, we identified a
      new pathogenic missense homozygous PEX1 mutation (p.Leu1026Pro, c.3077T>C) in two
      Moroccan syndromic deaf siblings from consanguineous parents. This variation is
      located in the P-loop containing nucleoside triphosphate hydrolase of protein
      domain and probably causes an alteration in the hydrolysis of ATP.

PMID- 28446957
TI  - Small copy-number variations involving genes of the FGF pathway in differences in
      sex development.
AB  - Retrospective chromosome microarray analysis of 83 genes within the fibroblast
      growth factor signaling pathway in 52 patients with heterogeneous differences in
      sex development (DSD) revealed small copy-number variations (CNVs) in ~31% (n=26)
      of investigated genes. Roughly half of these genes (39/83) are ?50 kb. This study
      highlights the potential involvement of small CNVs in disrupting normal gene
      function and dysregulating genes of the FGF pathway associated with DSD.

PMID- 28446958
TI  - Syndromic disorder of sex development due to a novel hemizygous mutation in the
      carboxyl-terminal domain of ATRX.
AB  - Alpha-thalassemia/mental retardation syndrome X-linked (ATRX; OMIM #301040),
      which is caused by mutations in the ATRX gene, is characterized by alpha
      thalassemia, distinct dysmorphic facies, psychomotor development delay and
      genital abnormalities. Here, we describe a neonatal case of syndromic disorder of
      sex development, harboring a novel hemizygous mutation, p.Asp2352fs*1 in the
      carboxyl-terminal domain of ATRX. Our study provides additional evidence that
      deletion of the carboxyl terminus of ATRX is associated with severe genital
      anomalies.

PMID- 28446960
TI  - Primary care Screening Questionnaire for Depression: reliability and validity of
      a new four-item tool.
AB  - BACKGROUND: Unidentified depression in primary care is a public health concern,
      globally. There is a need for brief, valid and easily administered tools in
      primary care. AIMS: To estimate reliability and validity of the newly developed
      Primary care Screening Questionnaire for Depression (PSQ4D), a four-item tool,
      with 'yes' or 'no' options. METHOD: PSQ4D was administered verbally (time
      required, <1 min) by primary care physicians to adult outpatients (n=827) in six
      primary care settings in Kerala, India. A psychiatrist evaluated each patient on
      the same day, using ICD-10 Diagnostic Criteria for Research, based on
      unstructured clinical interview. RESULTS: The Cronbach's alpha for internal
      consistency reliability was 0.80; kappa coefficient for test-retest reliability
      was 0.9 and that for interrater reliability was 0.72. At a score >=2, sensitivity
      was 0.96, specificity was 0.87, positive predictive value was 0.74, negative
      predictive value was 0.98, positive likelihood ratio was 7.4 and negative
      likelihood ratio was 0.05. CONCLUSIONS: When physician administered, PSQ4D has
      good reliability. At a cut-off score of >=2, it has high sensitivity and
      specificity to identify depressive disorder in primary care. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28446959
TI  - Gestational vitamin D deficiency and autism spectrum disorder.
AB  - BACKGROUND: There is growing interest in linking vitamin D deficiency with autism
      spectrum disorders (ASDs). The association between vitamin D deficiency during
      gestation, a critical period in neurodevelopment, and ASD is not well understood.
      AIMS: To determine the association between gestational vitamin D status and ASD.
      METHOD: Based on a birth cohort (n=4334), we examined the association between 25
      hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and
      neonatal sera, and ASD (defined by clinical records; n=68 cases). RESULTS:
      Individuals in the 25OHD-deficient group at mid-gestation had more than twofold
      increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to
      5.07, P=0.03) compared with the sufficient group. The findings persisted in
      analyses including children of European ethnicity only. CONCLUSIONS: Mid
      gestational vitamin D deficiency was associated with an increased risk of ASD.
      Because gestational vitamin D deficiency is readily preventable with safe,
      inexpensive and readily available supplementation, this risk factor warrants
      closer scrutiny. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The
      Royal College of Psychiatrists 2017. This is an open access article distributed
      under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC
      ND) license.

PMID- 28446961
TI  - A biopsychosocial model of violence when sleepwalking: review and
      reconceptualisation.
AB  - SUMMARY: Violence towards others during sleepwalking is relatively uncommon, but
      can result in serious injury or even death. Much of the research in this field
      has focused on the forensic consequences of violence during sleepwalking without
      sufficient attention to an understanding of the risk factors for violence during
      sleepwalking and the development of prevention and interventions based on these
      risk factors. This paper reviews the characteristics of impulsive violence in
      general and reconceptualises violence during sleepwalking as an extension of this
      prior vulnerability. We propose a biopsychosocial model of the risk for violence
      during sleepwalking that is supported through a review of empirical literature
      both within sleepwalking and violent behaviour more generally. Biological,
      psychological and social risk factors are hypothesised to mediate the
      relationship between sleepwalking and violence. Implications for prevention and
      treatment of this potentially fatal problem are discussed. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 28446962
TI  - Cardiac development: from current understanding to new regenerative concepts.

PMID- 28446963
TI  - New Lncs to mesendoderm specification.
AB  - Mammalian genomes are pervasively transcribed generating thousands of long
      noncoding RNAs (lncRNAs) with emergent regulatory roles. Many of these lncRNAs
      exhibit highly specialised expression patterns during development and typically
      flank and regulate key developmental factors. In this review, we discuss and
      summarise the latest advances in our understanding of the roles of lncRNAs during
      mesendoderm (ME) specification, a key step during gastrulation and the formation
      of the primitive streak (PS).

PMID- 28446964
TI  - Strategies for the acquisition of transcriptional and epigenetic information in
      single cells.
AB  - As the basic unit of living organisms, each single cell has unique molecular
      signatures and functions. Our ability to uncover the transcriptional and
      epigenetic signature of single cells has been hampered by the lack of tools to
      explore this area of research. The advent of microfluidic single cell technology
      along with single cell genome-wide DNA amplification methods had greatly improved
      our understanding of the expression variation in single cells. Transcriptional
      expression profile by multiplex qPCR or genome-wide RNA sequencing has enabled us
      to examine genes expression in single cells in different tissues. With the new
      tools, the identification of new cellular heterogeneity, novel marker genes,
      unique subpopulations, and spatial locations of each single cell can be acquired
      successfully. Epigenetic modifications for each single cell can also be obtained
      via similar methods. Based on single cell genome sequencing, single cell
      epigenetic information including histone modifications, DNA methylation, and
      chromatin accessibility have been explored and provided valuable insights
      regarding gene regulation and disease prognosis. In this article, we review the
      development of strategies to obtain single cell transcriptional and epigenetic
      data. Furthermore, we discuss ways in which single cell studies may help to
      provide greater understanding of the mechanisms of basic cardiovascular biology
      that will eventually lead to improvement in our ability to diagnose disease and
      develop new therapies.

PMID- 28446966
TI  - Monocytes and macrophages in cardiac injury and repair.
AB  - Myocardial infarction (MI) is one of the major contributors to worldwide
      morbidity and mortality. It is atherosclerosis' most dreadful complication and
      occurs after the supply of oxygenated blood to the heart is blocked.
      Understanding how cardiac tissue is injured and later regenerates is of crucial
      importance to improve the sequelae after the acute event. We now understand that
      the immune system substantially contributes to both the acute inflammatory
      response and the regenerative response that follow tissue injury after MI. In
      this review, we will focus on the role of monocytes and macrophages, which are
      cellular protagonists of the immune system, in acute cardiac injury and post-MI
      repair.

PMID- 28446967
TI  - Cardiac fibroblasts: more than mechanical support.
AB  - Fibroblasts are cells with a structural function, synthesizing components of the
      extracellular matrix. They are accordingly associated with various forms of
      connective tissue. During cardiac development fibroblasts originate from
      different sources. Most derive from the epicardium, some derive from the
      endocardium, and a small population derives from the neural crest. Cardiac
      fibroblasts have important functions during development, homeostasis, and
      disease. However, since fibroblasts are a very heterogeneous cell population no
      truly specific markers exist. Therefore, studying them in detail is difficult.
      Nevertheless, several lineage tracing models have been widely used. In this
      review, we describe the developmental origins of cardiac fibroblasts, comment on
      fibroblast markers and related lineage tracing approaches, and discuss the
      cardiac cell composition, which has recently been revised, especially in terms of
      non-myocyte cells.

PMID- 28446965
TI  - Role of circulating factors in cardiac aging.
AB  - Worldwide increase in life expectancy is a major contributor to the epidemic of
      chronic degenerative diseases. Aging, indeed, simultaneously affects multiple
      organ systems, and it has been hypothesized that systemic alterations in
      regulators of tissue physiology may regulate this process. Cardiac aging itself
      is a major risk factor for cardiovascular diseases and, because of the intimate
      relationship with the brain, may contribute to increase the risk of
      neurodegenerative disorders. Blood-borne factors may play a major role in this
      complex and still elusive process. A number of studies, mainly based on the
      revival of parabiosis, a surgical technique very popular during the 70s of the
      20th century to study the effect of a shared circulation in two animals, have
      indeed shown the potential that humoral factors can control the aging process in
      different tissues. In this article we review the role of circulating factors in
      cardiovascular aging. A better understanding of these mechanisms may provide new
      insights in the aging process and provide novel therapeutic opportunities for
      chronic age-related disorders.

PMID- 28446968
TI  - The role of transforming growth factor (TGF)-beta in the infarcted myocardium.
AB  - The adult mammalian heart has negligible regenerative capacity. Following
      myocardial infarction, sudden necrosis of cardiomyocytes triggers an intense
      inflammatory reaction that clears the wound from dead cells and matrix debris,
      while activating a reparative program. A growing body of evidence suggests that
      members of the transforming growth factor (TGF)-beta family critically regulate
      the inflammatory and reparative response following infarction. Although all three
      TGF-beta isoforms (TGF-beta1, -beta2 and -beta3) are markedly upregulated in the
      infarcted myocardium, information on isoform-specific actions is limited.
      Experimental studies have suggested that TGF-beta exerts a wide range of actions
      on cardiomyocytes, fibroblasts, immune cells, and vascular cells. The findings
      are often conflicting, reflecting the context-dependence of TGF-beta-mediated
      effects; conclusions are often based exclusively on in vitro studies and on
      associative evidence. TGF-beta has been reported to modulate cardiomyocyte
      survival responses, promote monocyte recruitment, inhibit macrophage pro
      inflammatory gene expression, suppress adhesion molecule synthesis by endothelial
      cells, promote myofibroblast conversion and extracellular matrix synthesis, and
      mediate both angiogenic and angiostatic effects. This review manuscript discusses
      our understanding of the cell biological effects of TGF-beta in myocardial
      infarction. We discuss the relative significance of downstream TGF-beta-mediated
      Smad-dependent and -independent pathways, and the risks and challenges of
      therapeutic TGF-beta targeting. Considering the high significance of TGF-beta
      mediated actions in vivo, study of cell-specific effects and dissection of
      downstream signaling pathways are needed in order to design safe and effective
      therapeutic approaches.

PMID- 28446970
TI  - The role of endobronchial ultrasound versus mediastinoscopy for non-small cell
      lung cancer.
AB  - This review provides an update on the current role of endobronchial ultrasound
      guided transbronchial needle aspiration (EBUS-TBNA) and mediastinoscopy (Med) in
      assessment of patients with non-small cell lung cancer (NSCLC). Invasive
      mediastinal lymph node (LN) staging is the major application for both of these
      techniques. Up until recently, Med was the gold standard for invasive mediastinal
      LN staging in NSCLC. However, EBUS-TBNA has shown to be equivalent, and in some
      studies better than Med for invasive staging of lung cancer. EBUS-TBNA offers
      access to N1 LNs and development of the thin convex probe EBUS (TCP-EBUS) will
      expand EBUS-TBNA access from the paratracheal region and central airways to more
      distal parabronchial regions allowing for more extensive N1 LN assessment and
      sampling more distal lung tumors. EBUS-TBNA is more cost-effective than Med and
      it is currently recommended as the test of first choice for invasive mediastinal
      LN staging in lung cancer. Confirmatory Med should be performed selectively in
      patients with high pretest probability of metastatic disease. Addition of
      esophageal ultrasound fine needle aspiration (EUS-FNA) may increase diagnostic
      yield of EBUS-TBNA mediastinal staging. Both Med and EBUS-TBNA can be used in
      primary lung cancer diagnosis, restaging of the mediastinum following neoadjuvant
      therapy and in diagnosis of lung cancer recurrence. In the future, a combination
      of EBUS-TBNA with or without EUS-FNA and Med is most likely going to provide the
      most optimal invasive assessment of the mediastinum in patients with lung cancer.
      The decision on test choice and sequence should be made on a case-by-case basis
      and factoring in local resources and expertise.

PMID- 28446972
TI  - Thermal ablation for asthma: current status and technique.
AB  - Bronchial thermoplasty (BT) is a novel technique used in the treatment of severe
      asthma. A catheter is advanced through the bronchoscope and directed
      radiofrequency waves are applied to the segmental bronchi to reduce airway smooth
      muscle mass. Several randomized clinical trials demonstrate improvement in
      quality of life and reduction in exacerbation rates after treatment. BT is a safe
      and cost effective treatment option for severe asthma which is refractory to
      medical treatment. Further studies are needed in order to better describe the
      mechanism of action and the asthma subphenotype that was best benefit from this
      treatment.

PMID- 28446971
TI  - Navigation bronchoscopy for diagnosis and small nodule location.
AB  - Lung cancer continues to be the most common cause of cancer death. Screening
      programs for high risk patients with the use of low-dose computed tomography (CT)
      has led to the identification of small lung lesions that were difficult to
      identify using previous imaging modalities. Electromagnetic navigational
      bronchoscopy (ENB) is a novel technique that has shown to be of great utility
      during the evaluation of small, peripheral lesions, that would otherwise be
      challenging to evaluate with conventional bronchoscopy. The diagnostic yield of
      navigational bronchoscopy however is highly variable, with reports ranging from
      59% to 94%. This variability suggests that well-defined selection criteria and
      standardized protocols for the use of ENB are lacking. Despite this variability,
      we believe that this technique is a useful tool evaluating small peripheral lung
      lesions when patients are properly selected.

PMID- 28446973
TI  - Bronchoscopic valves for prolonged air leak: current status and technique.
AB  - Unidirectional airway valves are devices used for the treatment of persistent air
      leaks (PALs) secondary to alveolar-pleural fistulas (APF) or bronchopleural
      fistulas (BPFs). These valves were originally developed as a non-surgical
      alternative to lung volume reduction surgery (LVRS) for patients with chronic
      obstructive pulmonary disease (COPD). Randomized trials investigating the use of
      valves for bronchoscopic LVRS did not lead to the Federal Drug Administration
      (FDA) approval, but stemming from these studies a Humanitarian Device Exemption
      (HDE) was granted to Spiration intrabronchial valves (IBVs) for the treatment of
      PALs. These valves are being increasingly utilized due to the effectiveness of
      IBVSs in reducing PALs, thus shortening duration of hospitalizations and
      minimizing the risk of hospital associated complications. The literature
      supporting the use of unidirectional airway valves for the bronchoscopic
      treatment of PALs is grounded primarily in case reports. While the current body
      of literature available to justify the use of unidirectional valves is limited to
      case series, current multicenter, randomized trials should provide further
      guidance regarding patient selection and effectiveness.

PMID- 28446969
TI  - MicroRNAs: pleiotropic players in congenital heart disease and regeneration.
AB  - Congenital heart disease (CHD) is the leading cause of infant death, affecting
      approximately 4-14 live births per 1,000. Although surgical techniques and
      interventions have improved significantly, a large number of infants still face
      poor clinical outcomes. MicroRNAs (miRs) are known to coordinately regulate
      cardiac development and stimulate pathological processes in the heart, including
      fibrosis or hypertrophy and impair angiogenesis. Dysregulation of these
      regulators could therefore contribute (I) to the initial development of CHD and
      (II) at least partially to the observed clinical outcomes of many CHD patients by
      stimulating the aforementioned pathways. Thus, miRs may exhibit great potential
      as therapeutic targets in regenerative medicine. In this review we provide an
      overview of miR function and elucidate their role in selected CHDs, including
      hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), ventricular
      septal defects (VSDs) and Holt-Oram syndrome (HOS). We then bridge this knowledge
      to the potential usefulness of miRs and/or their targets in therapeutic
      strategies for regenerative purposes in CHDs.

PMID- 28446974
TI  - Stents for airway strictures: selection and results.
AB  - Airway stents can provide effective and timely relief in patients with central
      airway obstruction. Silicone based stents are the most commonly used airway
      stents worldwide with a long track record of safety. Metallic stents continue to
      evolve from the earliest uncovered versions to a variety of newly designed
      covered stents. Despite the availability of a variety of stent materials and
      designs, minimal advances have been made towards innovation in stent technology
      and an ideal stent has unfortunately not yet been developed. Nevertheless, the
      first generation of biodegradable airway stents are available, work on drug
      eluted stents is in the pipeline and three-dimensional printing of a customized
      airway stent may be the future. In this review, we discuss selection and results
      for most commonly utilized airway stents.

PMID- 28446975
TI  - Current status of spray cryotherapy for airway disease.
AB  - The use of liquid nitrogen to treat skin and mucosal lesions is well understood
      in the dermatologic and gastrointestinal literature. Direct spray cryotherapy
      (SCT) in the airway has shown promising results in the treatment of esophageal
      premalignant and even invasive lesions. In the airway, several studies have shown
      it to be a safe, effective treatment for both benign and malignant disease. It is
      easily administered in the outpatient setting and can be repeated several times
      without undue side effects. In this article, we review the current literature on
      the use of SCT for the treatment of endobronchial lesions and also describe our
      own institutional experience of the use of SCT in the airway. The use of proper
      technique and airway venting is important in mitigating the complications of
      barotrauma from massive expansion of nitrogen upon conversion from the liquid to
      gaseous state. We also review some of the basic science principals behind the use
      of the cryotherapy to treat lesions in different tissues. We feel that SCT is a
      potential area for further research at both clinical and basic science level.

PMID- 28446976
TI  - Per-oral endoscopic myotomy for achalasia.
AB  - Symptoms in patients with achalasia are produced by outflow obstruction at the
      level of the lower esophageal sphincter (LES). As a consequence of neural
      destruction the LES does not undergo normal swallow-induced relaxation. In
      addition, the esophageal body loses normal peristaltic function and esophageal
      emptying is on the basis of gravity. All therapies for achalasia are palliative
      in that normal LES or esophageal body function cannot be restored. The efficacy
      of any therapy for achalasia is directly related to its ability to reduce the
      outflow obstruction at the LES. The three main treatment options are pneumatic
      dilatation, laparoscopic myotomy and partial fundoplication and per-oral
      endoscopic myotomy or per-oral esophageal myotomy (POEM). Details of the
      procedures and outcomes will be discussed.

PMID- 28446977
TI  - Endoscopic management of esophageal leaks.
AB  - Traditionally, gold standard treatment for an acute esophageal perforation has
      been operative repair. Over the past two decades, there has been a paradigm shift
      towards the use of esophageal stents. Recent advances in biomaterial allowed a
      new generation of stents to be manufactured that combined (I) a non-permeable
      covering; (II) radial force sufficient to occlude a transmural esophageal injury
      and (III) improved ease of removability. The amalgamation of these developments
      set the stage for utilizing esophageal stents as part of the management algorithm
      of an acute esophageal perforation. This provides a safe and less invasive
      treatment route in lieu of direct primary repair and its well-documented
      significant failure rate. Esophageal stent placement for failed operative repair
      or esophageal leaks also had the potential to minimize the need for esophageal
      resection and diversion. When included in a multimodality hybrid treatment
      protocol, esophageal stents can optimize healing success rates and minimize the
      risks of adverse complications. This review summarizes the modern history of
      esophageal stent use in the treatment of esophageal perforation as well as the
      evidenced based recommendations for the use of esophageal stent placement in the
      treatment of acute esophageal perforation.

PMID- 28446978
TI  - Optimizing the diagnosis and therapy of Barrett's esophagus.
AB  - The incidence of Barrett's esophagus (BE) in the Western world has increased over
      the last decades. BE is considered a premalignant lesion that can progress to
      esophageal adenocarcinoma (EAC), a highly aggressive malignancy with poor
      survival rates. The close association between BE and EAC highlights the need for
      an early diagnosis in order to improve survival and outcomes in this group of
      patients. Although the evidence for BE screening with conventional endoscopy is
      controversial and limited by cost-effectiveness studies, screening can be
      suggested in patients with chronic gastroesophageal reflux disease (GERD) and two
      or more risk factors for EAC. Less invasive techniques with lower costs and
      higher acceptability by the patients may be useful for screening in the general
      population. Several novel techniques have been described to aid in the early
      diagnosis and management of BE and dysplasia. However, these techniques have
      shown variable results with higher costs, the need of specific training, and
      variable inter-observer imaging interpretation, making its widespread
      implementation problematic. High-definition/high-resolution white-light endoscopy
      (WLE) continues to be a well-accepted technique for the evaluation and
      surveillance of patients with BE. Further studies are required in order to
      establish the efficacy of less invasive methods that can be performed in an
      outpatient setting for BE screening in higher risk individuals.

PMID- 28446979
TI  - Zenker's diverticulum: flexible versus rigid repair.
AB  - Zenker's diverticula (ZDs) are a relatively common cause of cervical dysphagia.
      Diagnosis is best by a good upper GI exam though upper endoscopy should be
      performed as well. Treatment is either by open, transcervical approaches or trans
      oral. Over the past 20 years, transoral approach has mostly replace transcervical
      approaches due to less pain, no scarring and a rapid recovery. Transoral
      approaches are either using rigid access or flexible endoscopy. Today, the most
      common approach is transoral stapling using a 12 mm laparoscopic linear cutting
      stapler. This has the drawbacks of requiring extreme neck extension, the massive
      size of the stapler making visualization mostly impossible and the current staple
      design that does not cut/staple all the way to the end of the blades-resulting in
      a residual pouch. Flexible endoscopy allows a more tailored approach under direct
      vision, the myotomy can even be extended beyond the diverticulum and onto the
      esophageal wall to minimize the risk of incomplete myotomy. Experienced
      endoscopists report high technical success and low complication. Success rates
      are similar but maybe slightly higher than with ridged transoral approaches or
      open surgery. Today, flexible endoscopic Zenkers is our preferred initial
      approach-with open or ridged being reserved for special indications.

PMID- 28446980
TI  - Preface to the 4th edition of European Perspective of Thoracic Surgery.

PMID- 28446981
TI  - Role of CXC group chemokines in lung cancer development and progression.
AB  - BACKGROUND: Clinical and translational research on lung cancer patients
      undergoing surgical treatment can provide valuable scientific data and unique
      opportunity to study tumor microenvironment. CXC chemokines, which are members of
      a big family of cytokines, are undoubtedly involved in tumor growth regulation
      and metastasizing pathways. For better understanding of CXC chemokine involvement
      in the process of carcinogenesis we have studied the cohort of early stage non
      small cell lung cancer patients undergoing surgery with curative intent. Our aim
      was to assess CXC chemokine ligand (CXCL) levels in patient blood samples
      representing systemic circulation and tumor microenvironment; assess CXC
      chemokine receptor (CXCR) expression in tumor tissue; and measure tumor
      infiltrating immune cell subpopulations. METHODS: A total of 54 patients with
      NSCLC had radical lung resection were enrolled in a single center prospective
      study and were followed-up annually for up to six years. During surgical
      procedure peripheral and tumor draining blood samples were taken. CXCL1, CXCL4,
      CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11 and CXCL12 levels were
      determined by ELISA, and chemokine concentration gradient was calculated. Tumor
      infiltrating immune cells (T helper cells, T cytotoxic cells, macrophages, B
      cells, plasma cells) and expression of CXCR1, CXCR2, CXCR3 and CXCR4 in tumor
      tissue were assessed by immunohistochemistry. RESULTS: Statistically significant
      decrease in chemokine concentration was found for CXCL4 (P=0.002) and CXCL5
      (P=0.011), and statistically significant concentration increase was found for
      CXCL7 (P=0.001) in total cohort. We have found statistically significant CXC
      chemokine concentration change for majority of chemokines-CXCL1 (P=0.002), CXCL4
      (P=0.001), CXCL5 (P=0.013), CXCL7 (P=0.036), CXCL8 (P=0.026), CXCL9 (P=0.034) and
      CXCL10 (P=0.032) in a group of patients who had good clinical result after
      surgery with no evidence of relapse, on the other hand patients with cancer
      recurrence including local and systemic cancer spread did not show any change of
      chemokine concentration in blood except for CXCL1 (P=0.041). We have also found
      that chemokine levels and gradients correlate with CXC receptor expression and
      number of tumor infiltrating immune cell subpopulations. CONCLUSIONS: Assessment
      of tumor microcirculation is useful for evaluation of different types of
      circulating biomarkers and application of our method can be very wide,
      integrating thoracic surgeons into translational cancer research.

PMID- 28446982
TI  - Management of chest trauma.
AB  - Trauma is the leading cause of death worldwide. Approximately 2/3 of the patients
      have a chest trauma with varying severity from a simple rib fracture to
      penetrating injury of the heart or tracheobronchial disruption. Blunt chest
      trauma is most common with 90% incidence, of which less than 10% require surgical
      intervention of any kind. Mortality is second highest after head injury, which
      underlines the importance of initial management. Many of these deaths can be
      prevented by prompt diagnosis and treatment. What is the role of the thoracic
      surgeon in the management of chest trauma in severely injured patients? When
      should the thoracic surgeon be involved? Is there a place for minimal invasive
      surgery in the management of severely injured patients? With two case reports we
      would like to demonstrate how the very specific knowledge of thoracic surgeons
      could help in the care of trauma patients.

PMID- 28446983
TI  - Thoracic sympathectomy for hyperhidrosis: from surgical indications to clinical
      results.
AB  - Sympathectomy and its variations have been performed in thoracic surgery for more
      than 100 years. However, its indications have undergone profound modifications in
      this period. Likewise, since then the surgical technique has also evolved
      dramatically up to the minimally invasive techniques worldwide accessible in
      present days. Currently, primary hyperhidrosis is, by far, the main indication
      for thoracic sympathectomy and this procedure is usually carried out
      thoracoscopically with excellent results. However, until today, hyperhidrosis is
      a part of thoracic surgery still surrounded by controversy, persisting as an open
      field over which some confusion still resides regarding its pathophysiology,
      terms definitions and operative approaches. The aim of this article is to provide
      a wide but easily comprehensible review of the theme, discussing and clarifying
      the major concepts with respect to its clinical presentation, all the presently
      available treatment options and strategies with their potential benefits and
      risks, the adequate patient selection for sympathectomy, as well as the
      postoperative clinical results.

PMID- 28446984
TI  - Salvage surgery after high-dose radiotherapy.
AB  - Salvage surgery is a relatively new entity in thoracic surgery and oncology.
      Salvage resection after radiotherapy refers to surgery as only remaining
      therapeutic option in patients who were treated with high-dose stereotactic
      radiotherapy (SRT) for early-stage lung cancer or full-dose chemoradiation for
      locally advanced lung cancer. Indications include locally progressive tumors,
      recurrent local or locoregional disease, or specific complications after
      radiotherapy such as lung abscesses or infected, necrotic cavities. Small,
      retrospective series demonstrate that salvage surgery after high-dose
      radiotherapy is feasible and may yield good long-term results. A clear
      distinction should be made between salvage surgery after SRT for early-stage lung
      cancer and salvage procedures after full-dose chemoradiation for lung cancers
      with locoregional extension into the mediastinum. Salvage surgery after SRT may
      be rather straightforward and in specific cases even feasible by a minimally
      invasive approach. In contrast, surgery after a full dose of chemoradiation
      delivered several months or years earlier, can be quite challenging and the
      dissection of the pulmonary artery and mediastinal lymph nodes technically
      demanding. Due to the more central irradiation an intrapericardial dissection is
      often required. To prevent a bronchopleural fistula protection of the bronchial
      stump with well-vascularized flaps is recommended. Each individual patient in
      whom salvage surgery is considered, should be discussed thoroughly within a
      multidisciplinary board, detailed cardiopulmonary functional evaluation is
      required, and the operation should be performed by an experienced team including
      a thoracic surgeon, anaesthesiologist and intensive care physician. At the
      present time only retrospective series are available. Carefully designed
      prospective studies are necessary to more precisely define indications and
      results of salvage surgery not only after SRT for peripherally localized lesions
      but also following full-dose chemoradiation for locoregionally advanced disease.

PMID- 28446985
TI  - Whack-a-mole strategy for multifocal ground glass opacities of the lung.
AB  - Ground glass opacity (GGO) is a good prognostic indicator for lung cancer and is
      useful for physicians to predict prognosis. Due to recent advances in computed
      tomography (CT), the chance to encounter GGO is rapidly increasing in clinical
      practice. Based on the studies on radiological pathological correlation, GGO
      represents pathological lepidic growth and consolidation on CT represents
      pathologically invasive components. Thus, consolidation tumor ratio 0.5 or less
      means pathological less invasiveness for lung cancer. Not a few studies have
      shown that sublobar resection is equivalent to lobectomy for radiological early
      lung cancers. Additionally, observation of GGO is one of the options for
      physicians. Indication of surgical intervention remains unclear. Physician
      observing GGO in practice should know the natural history of GGO to reach an
      optimal treatment decision. For multifocal GGO lesions clinical management is
      surely challenging. Whack-a-mole strategy, which means sublobar resection for
      radiological invasive cancer is one of the most promising strategies for such
      lesions.

PMID- 28446986
TI  - Sublobar resection for stage IA non-small cell lung cancer.
AB  - Advancements in the diagnosis, staging and management of lung cancer have all led
      to improvements in outcomes associated with sublobar resection. Lobectomy, for
      early stage lung cancers has been the treatment of choice for many years.
      However, there is mounting evidence that sublobar resection when applied to the
      appropriate patient population can provide not only excellent oncologic results
      but also equivalent survival to lobectomy. Therefore, it is time that we
      reevaluate the management of peripheral stage IA lung cancers.

PMID- 28446987
TI  - Blunt chest trauma: is there a place for rib stabilization?
AB  - Rib fractures are a common and highly morbid finding in patients with blunt chest
      trauma. Over the past decade, a renewed interest in (and instrumentation for) rib
      fixation in this cohort has occurred. Stabilization of the chest wall in this
      setting, particularly when a flail segment is present, is associated with
      significant reductions in the rates of respiratory failure, pneumonia, ICU stay,
      and mortality. Thoracic surgeons should remain actively involved in this evolving
      area of our specialty to further optimize patient outcomes.

PMID- 28446988
TI  - Thoracic surgery training in Europe-the perspective of a trainee.
AB  - Duration and content of Thoracic surgery training differs considerably across
      Europe, leading to unequal levels of knowledge, skills and attitudes at the time
      of graduation as a specialist. The European Board of Thoracic Surgery examination
      strives to overcome these regional differences by offering a diploma to achieve
      harmonization and equal qualified certification. The HERMES initiative, driven by
      a joint task force from European Society of Thoracic Surgeons (ESTS) and European
      Respiratory Society (ERS) is currently establishing a consensual syllabus and
      curriculum for Thoracic Surgery to standardize content of training and achieve
      equal levels of qualification all-over Europe. In this context, new opportunities
      in teaching and learning have become available and should be considered to
      support and encourage for beneficial development in the future. International
      platforms are the key for connecting with experts and other trainees and are
      provided by annual meetings and within the ESTS School.

PMID- 28446989
TI  - The microbiome, microbial-generated proinflammatory neurotoxins, and Alzheimer's
      disease.

PMID- 28446990
TI  - Demonstration of an Integrated Pest Management Program for Wheat in Tajikistan.
AB  - Wheat is an important food security crop in central Asia but frequently suffers
      severe damage and yield losses from insect pests, pathogens, and weeds. With
      funding from the United States Agency for International Development, a team of
      scientists from three U.S. land-grant universities in collaboration with the
      International Center for Agricultural Research in Dry Areas and local
      institutions implemented an integrated pest management (IPM) demonstration
      program in three regions of Tajikistan from 2011 to 2014. An IPM package was
      developed and demonstrated in farmer fields using a combination of crop and pest
      management techniques including cultural practices, host plant resistance,
      biological control, and chemical approaches. The results from four years of
      demonstration/research indicated that the IPM package plots almost universally
      had lower pest abundance and damage and higher yields and were more profitable
      than the farmer practice plots. Wheat stripe rust infestation ranged from 30% to
      over 80% in farmer practice plots, while generally remaining below 10% in the IPM
      package plots. Overall yield varied among sites and years but was always at least
      30% to as much as 69% greater in IPM package plots. More than 1,500 local farmers
      40% women-were trained through farmer field schools and field days held at the
      IPM demonstration sites. In addition, students from local agricultural
      universities participated in on-site data collection. The IPM information
      generated by the project was widely disseminated to stakeholders through peer
      reviewed scientific publications, bulletins and pamphlets in local languages, and
      via Tajik national television.

PMID- 28446991
TI  - Sugarcane Aphid (Hemiptera: Aphididae): A New Pest on Sorghum in North America.
AB  - In 2013, the sugarcane aphid, Melanaphis sacchari (Zehntner) (Hemiptera:
      Aphididae), a new invasive pest of sorghum species in North America, was
      confirmed on sorghum in 4 states and 38 counties in the United States. In 2015,
      the aphid was reported on sorghum in 17 states and over 400 counties as well as
      all sorghum-producing regions in Mexico. Ability to overwinter on living annual
      and perennial hosts in southern sorghum-producing areas and wind-aided movement
      of alate aphids appear to be the main factors in its impressive geographic spread
      in North America. Morphological characteristics of the sugarcane aphid include
      dark tarsi, cornicles, and antennae, allowing easy differentiation from other
      aphids on the crop. Sugarcane aphid damages sorghum by removing sap and covering
      plants with honeydew, causing general plant decline and yield loss. Honeydew and
      sooty mold can disrupt harvesting. The aphid's high reproductive rate on
      susceptible sorghum hybrids has resulted in reports of yield loss ranging from
      10% to greater than 50%. In response, a combination of research-based data and
      field observations has supported development of state extension identification,
      scouting, and treatment guides that aid in initiating insecticide applications to
      prevent yield losses. Highly efficacious insecticides have been identified and
      when complemented by weekly scouting and use of thresholds, economic loss by
      sugarcane aphid can be minimized. Some commercial sorghum hybrids are partially
      resistant to the aphid, and plant breeders have identified other lines with
      sugarcane aphid resistance. A very diverse community of predators and parasitoids
      of sugarcane aphid has been identified, and their value to limit sugarcane aphid
      population growth is under investigation.

PMID- 28446992
TI  - Multimodality Imaging of Calcinosis of Chronic Renal Failure.
AB  - Secondary tumoral calcinosis (STC) refers to periarticular calcified masses
      associated with an identifiable condition. The most common of these identifiable
      conditions is a chronic renal failure. We present a unique case in which massive
      periarticular masses in a patient with calcinosis of chronic renal failure (CCRF)
      are demonstrated in the shoulder and hip on sonography, radiography and computed
      tomography (CT).

PMID- 28446993
TI  - Minimally Invasive Surgical Techniques for Management of Painful Metastatic and
      Primary Spinal Tumors.
AB  - Patients with metastatic spinal disease are affected by disabling pain. The
      treatment of spinal metastases is focused on pain reduction and improvement in
      quality of life. Until recently, many patients with metastatic spinal disease did
      not qualify as surgical candidates due to the risks of surgery and length of
      recovery period. However, recent advances in minimally invasive surgery such as
      kyphoplasty and vertebroplasty allow patients to safely undergo surgery for pain
      relief with a short recovery period. The studies reviewed here suggest that
      vertebral augmentation is successful in reducing pain and disability scores in
      patients with painful metastases and multiple myeloma and are a safe modality to
      provide lasting pain relief. As the use of kyphoplasty and vertebroplasty for
      treatment of vertebral metastases is becoming more common, new combinations of
      cement augmentation with other techniques such as percutaneous pedicle screws and
      radiofrequency ablation are being explored. The implementation of kyphoplasty and
      vertebroplasty, in conjunction with other minimally invasive surgical techniques
      as well as nonsurgical modalities, may lead to the best palliative management of
      cancer patients with spinal metastases and help them ultimately achieve a better
      quality of life.

PMID- 28446994
TI  - Frequency and volumetry of infraorbital ethmoid cells (Haller cells) on cone-beam
      computed tomograms (CBCT) of the mid-face.
AB  - Objective: The aim of this study was to determine the frequency and morphology of
      Haller cells using a new radiological technique that allows examination of the
      facial skull. Material and methods: In a single center retrospective cohort study
      the cone-beam computed tomography (CBCT) volume data of the maxillary sinus of
      199 patients were analysed (398 paranasal sinuses). If Haller cells were found,
      their capacity was determined. If orthopantomograms (OPG) were taken in a narrow
      time frame around the CBCT investigation, the rate of correspondence of the
      radiological findings was determined. The correlation between frequency of Haller
      cells and age and gender was calculated. Results: Out of 199 patients 47 showed
      at least one Haller cell (23.62%). The total number of Haller cells was 64.
      Correspondence was rare in the same case between the results from different
      examination procedures with respect to the target object. Conclusions: Bony
      variants of paranasal sinuses can be analysed using CBCT as an alternative to
      computed tomography (CT), whereas OPG images do not reliably detect Haller cells.

PMID- 28446995
TI  - Marginalized mixture models for count data from multiple source populations.
AB  - Mixture distributions provide flexibility in modeling data collected from
      populations having unexplained heterogeneity. While interpretations of regression
      parameters from traditional finite mixture models are specific to unobserved
      subpopulations or latent classes, investigators are often interested in making
      inferences about the marginal mean of a count variable in the overall population.
      Recently, marginal mean regression modeling procedures for zero-inflated count
      outcomes have been introduced within the framework of maximum likelihood
      estimation of zero-inflated Poisson and negative binomial regression models. In
      this article, we propose marginalized mixture regression models based on two
      component mixtures of non-degenerate count data distributions that provide
      directly interpretable estimates of exposure effects on the overall population
      mean of a count outcome. The models are examined using simulations and applied to
      two datasets, one from a double-blind dental caries incidence trial, and the
      other from a horticultural experiment. The finite sample performance of the
      proposed models are compared with each other and with marginalized zero-inflated
      count models, as well as ordinary Poisson and negative binomial regression.

PMID- 28446996
TI  - Barrett's esophagus: best practices for treatment and post-treatment
      surveillance.
AB  - Barrett's esophagus (BE) is a premalignant condition that increases the risk of
      esophageal adenocarcinoma (EAC). Significantly more common in the Western world,
      risk factors include increased age, male sex, white race, gastro-esophageal
      reflux disease (GERD), central obesity, and cigarette smoking. The rates of
      progression to cancer depend on the grade of Barrett's dysplasia. Screening for
      BE is recommended in patients with GERD and additional risk factors. Endoscopic
      surveillance of patients with BE likely improves overall outcomes. Advanced
      endoscopic imaging can help increase the efficiency of current endoscopic
      surveillance. Endoscopic therapy is safe and effective for the treatment of
      dysplastic BE and intramucosal EAC, but ongoing surveillance following treatment
      is necessary. This review will cover screening, surveillance, advanced imaging,
      chemoprevention, endoscopic treatment, and post-treatment surveillance of BE.

PMID- 28446997
TI  - Endoscopic submucosal dissection and endoscopic mucosal resection for early stage
      esophageal cancer.
AB  - Mortality from esophageal cancer remains high despite advances in medical
      therapy. Although the incidence of squamous cell carcinoma of the esophagus
      remains unchanged, the incidence of the esophageal adenocarcinoma has increased
      over time. Gastroesophageal reflux disease (GERD and obesity are contributing
      factors to the development of Barrett's esophagus and subsequent development of
      adenocarcinoma. Early recognition of the disease can lead to resection of
      esophageal cancer prior to the development of lymphovascular invasion. Various
      modalities have been implemented to aid identification of precancerous lesions
      and early esophageal cancer. Chromoendoscopy, narrowband imaging and endoscopic
      ultrasound examination are typically used for evaluating early esophageal
      lesions. Recently, confocal laser endomicroscopy (CLE) and volumetric laser
      scanning were implemented with promising results. Endoscopic management of early
      esophageal cancer may be done using endoscopic mucosal resection (EMR) or
      endoscopic submucosal dissection (ESD). Both techniques allow resection of the
      mucosa (and possibly a portion of the submucosa) containing the early tumor
      without interruption of deeper layers. A submucosal injection creating a cushion
      coupled with snare resection or cap assisted mucosal suction followed by ligation
      and snare resection are the most common techniques of EMR. EMR can remove lesions
      less than 2 cm in size en bloc. Larger lesions may require resection in piecemeal
      fashion. This may limit assessment of the margins of the lesion and orienting the
      lesion's border. ESD offers en bloc dissection of the lesion regardless of its
      size. ESD is performed with specialized needle knives, which allow incision
      followed by careful dissection of the lesion within the submucosal layer. Tumor
      recurrence after ESD is rare but the technique is labor intensive and has an
      increased risk of perforation. Esophageal stenosis remains a concern after
      extensive EMR or ESD. Dilation with balloon or stent placement is usually
      sufficient to treat post-resection stenosis.

PMID- 28446998
TI  - Pathology of esophageal cancer and Barrett's esophagus.
AB  - Esophageal cancer is a serious malignancy with high mortality. The two common
      distinctive pathologic subtypes of esophageal cancer are squamous cell carcinoma
      and adenocarcinoma. These differ with regards to etiology, ethnic distribution,
      pathogenesis, and location in the esophagus. The precursor lesions are also
      unique to each subtype. Squamous cell carcinoma is more common in East Asia, is
      linked to smoking and tobacco use, more commonly involves the middle esophagus,
      and the precursor lesion is squamous dysplasia. Adenocarcinoma is more common in
      the United States and certain European countries, associated with obesity and
      gastroesophageal reflux disease (GERD), more commonly involves the distal
      esophagus, and the precursor lesion is Barrett's esophagus. Endoscopic
      surveillance with biopsy evaluation is the standard of care in high-risk groups.
      Endoscopic ablative therapies for early cancers have lower morbidity than
      surgery. Despite increased awareness, identification of high-risk groups and
      endoscopic surveillance, a large proportion of patients present with advanced
      cancers. Surgery and chemoradiation, either in neo-adjuvant or adjuvant setting,
      is the usual treatment for patients with advanced but resectable esophageal
      cancers. The prognosis and further management largely depends upon the pathologic
      tumor-node-metastasis (TNM) staging provided by the American Joint Committee on
      Cancer (AJCC) and the International Union against Cancer. Currently, the 7th
      edition of TNM staging system is being applied for prognostication and this is
      more focused on pathologic evaluation. Eighth edition of AJCC/UICC TNM staging
      has been introduced and will be implemented for clinical use in 2018.

PMID- 28446999
TI  - Minimally invasive staging of esophageal cancer.
AB  - Esophageal cancer is one of the most common malignancies in the world today and
      the sixth-leading cause of cancer-related mortality. Accurate preoperative
      staging of esophageal cancer is imperative to the selection of appropriate
      treatments. Patients with esophageal carcinomas typically undergo a multimodality
      staging process including noninvasive imaging techniques, such as computed
      tomography (CT) and positron emission tomography (PET), as well as endoscopic
      ultrasound (EUS), which is slightly more invasive. Minimally invasive surgical
      staging, with laparoscopy, occasionally in combination with video-assisted
      thoracoscopy, is used in the staging process at select institutions and has been
      shown to be more accurate than noninvasive staging modalities. Two major
      advantages of minimally invasive surgical staging over conventional techniques
      are the improved assessment of locoregional disease and enhanced identification
      of distant metastases. These advantages decrease the likelihood that the patient
      will undergo a nontherapeutic laparotomy. Currently, no clear consensus exists
      regarding which patients with esophageal cancer would benefit most from the
      addition of minimally invasive surgical staging. We have, however, found that
      minimally invasive surgical staging with laparoscopy is particularly valuable in
      detection of occult distant metastases. In this article, we summarize the staging
      modalities for esophageal cancer including minimally invasive surgical staging.

PMID- 28447000
TI  - 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric
      junction: application to clinical practice.
AB  - The 8th edition of the American Joint Committee on Cancer (AJCC) staging of
      epithelial cancers of the esophagus and esophagogastric junction (EGJ) presents
      separate classifications for clinical (cTNM), pathologic (pTNM), and
      postneoadjuvant (ypTNM) stage groups. Histopathologic cell type markedly affects
      survival of clinically and pathologically staged patients, requiring separate
      groupings for each cell type, but ypTNM groupings are identical for both cell
      types. Clinical categories, typically obtained by imaging with minimal histologic
      information, are limited by resolution of each method. Strengths and shortcomings
      of clinical staging methods should be recognized. Complementary cytology or
      histopathology findings may augment imaging and aid initial treatment decision
      making. However, prognostication using clinical stage groups remains coarse and
      inaccurate compared with pTNM. Pathologic staging is losing its relevance for
      advanced-stage cancer as neoadjuvant therapy replaces esophagectomy alone.
      However, it remains relevant for early-stage cancers and as a staging and
      survival reference point. Although pathologic stage could facilitate decision
      making, its use to direct postoperative adjuvant therapy awaits more effective
      treatment. Prognostication using pathologic stage groups is the most refined of
      all classifications. Postneoadjuvant staging (ypTNM) is introduced by the AJCC
      but not adopted by the Union for International Cancer Control (UICC). Drivers of
      this addition include absence of equivalent pathologic (pTNM) categories for
      categories peculiar to the postneoadjuvant state (ypT0N0-3M0 and ypTisN0-3M0),
      dissimilar stage group compositions, and markedly different survival profiles.
      Thus, prognostication is specific for patients undergoing neoadjuvant therapy.
      The role of ypTNM classification in additional treatment decision-making is
      currently limited. Precision cancer care advances are necessary for this
      information to be clinically useful.

PMID- 28447001
TI  - Overview of esophageal cancer.
AB  - Esophageal cancer is a male-dominant aggressive malignancy and a leading cause of
      cancer-related mortality worldwide. Squamous cell carcinoma and adenocarcinoma
      are the two predominant histological subtypes with varying geographical and
      racial distribution. Globally, squamous cell carcinoma remains the most common
      histological type. In Western countries, however, adenocarcinoma has become the
      leading histological subtype, corresponding to a rise in the incidence of
      obesity, gastro-esophageal reflux disease and Barrett's esophagus. The risk of
      esophageal adenocarcinoma conferred by Barrett's esophagus depends on factors
      such as genomic instability, race and gender of the patient. Treatment requires a
      multidisciplinary team approach and optimal therapy is still debated. Endoscopic
      therapies, including radiofrequency ablation, endoscopic mucosal resection and
      endoscopic sub mucosal dissection, have become the standard treatment modality
      for Barrett's esophagus and early carcinoma. Multimodal treatment, which includes
      chemotherapy, radiation therapy followed by surgical resection or without
      surgical resection, in varying orders remains the main mode of treatment for most
      patients. Minimally invasive surgical approaches have become the standard for
      esophagectomy and the current literature has demonstrated similar oncological
      outcomes with reduced morbidity. Recently, there has been a modest improvement in
      the overall survival of patients with esophageal cancer.

PMID- 28447002
TI  - Alternative conduits for esophageal replacement.
AB  - Replacement of the native esophagus after esophagectomy is a problem that has
      challenged surgeons for over a century. Not only must the conduit be long enough
      to bridge the distance between the cervical esophagus and the abdomen, it must
      also have a reliable vascular supply and be sufficiently functional to allow for
      deglutition. The stomach, jejunum, and colon (right, left or transverse) have all
      been proposed as potential solutions. The stomach has gained favor for its
      length, reliable vascular supply and need for only a single anastomosis. However,
      there are times when the stomach is unavailable for use as a conduit. It is in
      these instances that an esophageal surgeon must have an alternative conduit in
      their armamentarium. In this paper, we will briefly discuss the technical aspects
      of jejunal and colonic interposition. We will review the recent literature with a
      focus on early and late outcomes. The advantages and disadvantages of both
      options will be reviewed.

PMID- 28447003
TI  - Salvage esophagectomy for persistent or recurrent disease after definitive
      chemoradiation.
AB  - Locoregionally advanced esophageal cancer is treated by some oncologists with
      definitive chemoradiation. The optimal strategy to treat persistent or recurrent
      disease after definitive chemoradiation is controversial. We reviewed the
      literature to determine current treatment options and optimal approaches. Salvage
      esophagectomy of relapsed or recurrent esophageal cancer has traditionally been
      associated with increased risk. Modern literature, however, suggests that in
      specialized high volume centers the risk of salvage esophagectomy when
      accompanied with various risk-reducing approaches (anastomosis in non-radiated
      esophagus, omental transposition, selective use of alternative conduits and two
      stage procedures) is similar to planned esophagectomy after neoadjuvant
      chemoradiation. Long-term survival rates following salvage esophagectomy are also
      achievable and similar to planned esophagectomy. Since there are no other
      potentially curable treatment options, we recommend that all physiologically fit
      patients with locoregionally persistent or recurrent esophageal cancer after
      definitive chemoradiation be referred to a specialized high volume esophageal
      center for salvage esophagectomy.

PMID- 28447004
TI  - Principles of esophageal cancer surgery, including surgical approaches and
      optimal node dissection (2- vs. 3-field).
AB  - Surgery for esophageal carcinoma and carcinoma of the gastro-esophageal junction
      (GEJ) is considered as one of the most complex and challenging interventions on
      the digestive tract. This is due to the intimate relations with vital structures
      in the chest and the tendency of early lymphatic dissemination via a dense and
      complex submucosal network. This review article discusses the different aspects
      of surgical access routes in the light of the ever-evolving techniques, in
      particular the minimally invasive esophagectomy (MIE). The aspects of surgical
      approach are inextricably linked to the still ongoing debate on extent of
      lymphadenectomy, a debate that is obtaining a new dimension in view of the widely
      applied neoadjuvant therapy protocols as well as in view of the increasing
      importance of quality of life aspects after surgery. Finally, the authors provide
      a practical and patient tailored approach as applied in their center.

PMID- 28447006
TI  - What is the role of neoadjuvant chemotherapy, radiation, and adjuvant treatment
      in resectable esophageal cancer?
AB  - The majority of patients with operable esophageal cancers present with locally
      advanced disease, for which surgical resection as a sole treatment modality has
      been historically associated with poor survival. Even following radical
      resection, most of these patients will eventually succumb to their disease due to
      distant metastasis. For this reason, there has been intense interest in the role
      of neoadjuvant therapy. Neoadjuvant therapy primarily consists of either
      chemotherapy, radiation therapy, or a combination of the two. Multiple studies of
      variable scope, design, and patient characteristics have been conducted to
      determine whether neoadjuvant therapy is warranted, and-if so-what is the best
      modality of treatment. Despite nearly three decades of study, decisions regarding
      neoadjuvant therapy for esophageal cancer remain controversial. Regardless, the
      available evidence provided by large, prospective studies supports preoperative
      chemotherapy as opposed to surgery alone. Therefore, in our opinion, there is no
      longer any question as to whether induction therapy is appropriate for locally
      advanced esophageal cancer. Less clear, however, is the evidence that the
      addition of radiation to chemotherapy in the preoperative setting is superior to
      neoadjuvant chemotherapy alone. Our group generally advocates for neoadjuvant
      chemotherapy alone followed by radical esophageal resection. The data for
      adjuvant therapy are soft, and particularly troubling is the high rate of
      treatment drop out in trials studying adjuvant therapy. Therefore, we strongly
      prefer neoadjuvant chemotherapy and reserve adjuvant chemotherapy for those rare,
      highly selected patients-patients with T1 tumors, for example-who do not receive
      neoadjuvant treatment and are found to have occult nodal disease at the time of
      surgery.

PMID- 28447005
TI  - Future directions in esophageal cancer therapy.
AB  - Resection techniques for esophageal carcinoma continue to evolve, from endoscopic
      mucosal resection or endoscopic submucosal dissection for early stage disease to
      standard and robot-assisted minimally invasive esophagectomy as part of
      multimodal therapy for locally advanced disease. Though currently limited to
      assessing conduit perfusion and sentinel lymph nodes, embedded technology in the
      robotic surgical platform will likely play an expanded role during esophagectomy
      in the future. The use of targeted therapies, checkpoint inhibitors, engineered
      immune cell therapy, and cancer vaccines show promise in the treatment of
      systemic disease. Radiation therapy techniques are becoming increasingly
      sophisticated and they may play a more active role in stage IV disease in the
      future.

PMID- 28447007
TI  - Minimally invasive esophagectomy: the Brigham and Women's Hospital experience.

PMID- 28447008
TI  - Robotic assisted minimally invasive esophagectomy (RAMIE): the University of
      Pittsburgh Medical Center initial experience.

PMID- 28447010
TI  - Esophageal cancer.

PMID- 28447009
TI  - Robotic esophagectomy: the Moffitt Cancer Center experience.

PMID- 28447011
TI  - Guest Editor Introduction.

PMID- 28447012
TI  - Erratum to degenerative mitral valve disease-contemporary surgical approaches and
      repair techniques.
AB  - [This corrects the article DOI: 10.21037/acs.2016.11.03.].

PMID- 28447013
TI  - Is there a need for investigator-initiated research?

PMID- 28447014
TI  - Narrative writing: Effective ways and best practices.
AB  - A narrative is a brief summary of specific events experienced by patients, during
      the course of a clinical trial. Narrative writing involves multiple activities
      such as generation of patient profiles, review of data sources, and
      identification of events for which narratives are required. A sponsor outsources
      narrative writing activities to leverage the expertise of service providers which
      in turn requires effective management of resources, cost, time, quality, and
      overall project management. Narratives are included as an appendix to the
      clinical study report and are submitted to the regulatory authorities as a part
      of dossier. Narratives aid in the evaluation of the safety profile of the
      investigational drug under study. To deliver high-quality narratives within the
      specified timeframe to the sponsor can be achieved by standardizing processes,
      increasing efficiency, optimizing working capacity, implementing automation, and
      reducing cost. This paper focuses on effective ways to design narrative writing
      process and suggested best practices, which enable timely delivery of high
      quality narratives to fulfill the regulatory requirement.

PMID- 28447015
TI  - Data sharing: A viable resource for future.
AB  - Clinical trials and research studies are being conducted worldwide at a rampant
      pace leading to generation of large amount of data. However, to reap the benefits
      of the data generated it is important that this data is shared with the general
      public without which it can be deemed useless. Despite its importance being known
      to us, data sharing does not come without its share of problems and it is not as
      easy to execute as it sounds on-paper. Over the past few years, multiple coveted
      organizations around the world involved in research activities have come up with
      their respective guidelines and initiatives to make sure the sharing of research
      data is smooth and ethical. Developing countries like India have made a few
      strides in the right direction with some initiatives in-place, but there still
      seems a long way to go before unanimous data sharing can be a reality. The
      stakeholders may have to face certain possible repercussions due to data sharing
      but there is no doubt that if done in the right way, it can lead to universal
      development.

PMID- 28447016
TI  - Deriving meaningful insights from clinical trial and postmarketing safety data:
      Perspectives from India.
AB  - Today, drug safety data collection in India is both manual and electronic with
      reporting of potential overlapping and duplicate data, which is likely incomplete
      for further review and analysis. Furthermore, standardized data collection and
      timelines are not aligned with international standards. Complete coverage of
      safety data from all sources throughout the life of the drug cannot be ensured.
      There is no requirement to submit periodic safety data in clinical trials to
      regulatory authority. There is clearly a lack of emphasis on deriving meaningful
      safety data insights for ensuring patient safety. Efforts toward the early
      detection of drug safety issues are minimal. There is no mandate to publicly
      disclose drug safety findings. Benefit-risk evaluation of investigational and
      marketed products cannot be assured merely through annual status reports and
      periodic safety update reports, respectively. Focused initiatives involving
      stakeholders from regulatory, health-care, and pharmaceutical industries are
      required to change the current situation and enable derivation of meaningful
      insights from safety data. Equal emphasis on assessing real-time safety of the
      drugs and protection of patients' rights, safety, and well-being is required.
      Periodic safety data reporting in clinical trials, proactive safety data
      collection related to potential safety concerns, electronic medical records,
      electronic expedited reporting, collection of targeted data from stakeholders,
      and standardized and harmonized data collection aligned to the International
      Council for Harmonization guidelines are required. The Central Drugs Standard
      Control Organization should implement requirements to submit Development Safety
      Update Reports, Periodic Benefit-Risk Evaluation Reports, and Risk Management
      Plans. Access to clinical trials and postmarketing safety data through central
      repository would enable researchers to explore the data for application in
      clinical practice.

PMID- 28447017
TI  - In sickness and in health: Clinical research and social media.
AB  - In this "digital age," the model of healthcare is changing rapidly, primarily in
      the area of communication that is happening among the major stakeholders each
      minute. Patients, being the central point of the importance of all the work and
      development, are more empowered than ever with information from various sources,
      among which social media is leading from the front. This article reviews how
      social media engages healthcare service providers, service seekers, and
      regulatory authorities. If the gaps in the current regulations are filled, better
      healthcare outputs can be triggered. This article also briefly explores the
      popular healthcare applications launched by leading pharmaceutical companies,
      encompassing the big data advantage, in this evolving era of patient centricity.

PMID- 28447018
TI  - Predictors of over-the-counter medication: A cross-sectional Indian study.
AB  - CONTEXT: The determinants of over-the-counter (OTC) medication need to be
      understood to design adequate drug information policies. AIM: To determine the
      prevalence and predictors of OTC medication among the adult population of
      Berhampur town in Odisha, India. SETTINGS AND DESIGN: It was a prospective, cross
      sectional, observational study carried out in the private retail pharmacy on a
      convenience sample of 880 adults over a period of 6 months at Berhampur, Odisha,
      India. MATERIALS AND METHODS: Medication use behavior was explored using a data
      collection form that had three parts. The first part captured data on the
      sociodemographic characteristics of drug consumers. The second and third part
      collected data on drug history and attitude toward the available health-care
      facility, respectively. STATISTICAL ANALYSIS: Descriptive statistics was used to
      represent the prevalence of OTC medication. Odds ratio and 95% confidence
      intervals (CIs) were used to determine the predictors of OTC medication. RESULTS:
      The overall prevalence of OTC medication use was 18.72% (95% CI: 15.34-47.16%).
      Younger age, male gender, lower income, and poor lifestyle were the predictors of
      OTC medication. Perception of poor accessibility to health care, the presence of
      chronic diseases and having a symptom count of more than two significantly
      increased the likelihood of OTC medication (P < 0.05). CONCLUSIONS:
      Sociodemographic profile, drug history, and attitude toward health-care
      availability in the locality can predict OTC medication behavior. Interventions
      aimed at changing the perceptions of the public regarding accessibility,
      affordability of the health care is likely to influence OTC medication behavior
      and make it safer.

PMID- 28447019
TI  - A cross-sectional study: Need of equal respect for all professionals in the
      Institutional Ethics Committees' composition.
AB  - BACKGROUND: The composition of the Institutional Ethics Committee (IEC) with an
      equal respect plays a major role in evaluating research proposals to ensure the
      safety of the subjects and ethical quality of research project. It is mandatory
      that all research projects with an involvement of human subjects should be
      approved by the IEC before commencement. AIM: To find out the equality of respect
      to members of IEC irrespective of nature of their profession. MATERIALS AND
      METHODS: Methods include a cross-sectional study, the general information and
      member composition, multidisciplinary nature, independent performance,
      competence, decision capability, professionally biased of IECs in health research
      institutions of Punjab, India. A structured self-administered questionnaire was
      developed and provided to all health/research institutions providing the
      graduate/postgraduate education in medical sciences under the jurisdiction of
      Baba Farid University of Health Sciences, Faridkot, Punjab, India. RESULTS: Of
      the total 142 institutes, only 80 (56% response rate) institutes responded to the
      questionnaire. Of the 80 institutes which responded, 65 institutes (81.25%) had
      IEC, while 15 (18.75%) institutes lacked IEC. The compositions of only 22% IECs
      were in compliance to Drug Controller General of India (DCGI) guidelines and only
      nine (14%) institutes of the state of Punjab had approval from the DCGI.
      CONCLUSION: Study clearly indicates the carelessness of regulatory bodies and
      lack of fair practices toward constitution of the IEC. The ratio of nonscientific
      members (ethicist, philosopher, and layperson) in the IEC composition was
      incredibly low. This study also reveals the professionally biased and
      noncompliance with schedule Y guideline in relation to the representation of
      lawyers, ethicists, and nonscientific members.

PMID- 28447020
TI  - Impact of educational intervention on knowledge, attitude and awareness of good
      clinical practice among health care providers.
AB  - BACKGROUND: Clinical trials play an important role in the generation of evidence
      based data in health care practices. To ensure the credibility of data and the
      safety and well-being of the patients Good clinical practice (GCP) guidelines
      play an important role. At present, we have little knowledge about awareness of
      GCP guidelines among health care providers in India. AIM: To assess the level of
      awareness, and perception of the health care providers toward GCP and subsequent
      change in these after a dayer training session on GCP guidelines. SETTINGS AND
      DESIGN: A cross-sectional descriptive questionnaire-based study was conducted
      amongst health care providers, that is, doctors, dentists, nurses of a Tertiary
      Health Care and Teaching Institute. MATERIALS AND METHODS: Participants were
      given descriptive questionnaire; they completed the questionnaire before and
      after undergoing a day training program in GCP guidelines. STATISTICAL ANALYSIS
      USED: The impact of the effectiveness of educational intervention among
      healthcare professionals was evaluated by two-tailed Z-test. RESULTS: Out of 120
      participants, 80 were medical doctors, 20 dental doctors, and 20 nurses. A dayse
      training program on GCP guidelines was found to increase positive attitudes
      toward various aspects of clinical trials. CONCLUSION: A day's training program
      on GCP guidelines may help to increase the knowledge as well as awareness about
      principles and techniques of clinical research, which will increase the
      credibility of clinical research in the country.

PMID- 28447021
TI  - Clinical trials in dentistry in India: Analysis from trial registry.
AB  - INTRODUCTION: Evidence-based practice requires clinical trials to be performed.
      In India, if any clinical trial has to be performed, it has to be registered with
      clinical trial registry of India. Studies have shown that the report of clinical
      trials is poor in dentistry. Hence, the present study has been conducted to
      assess the type and trends of clinical trials being undertaken in dentistry in
      India over a span of 6 years. METHODOLOGY: All the clinical trials which were
      registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from
      January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental."
      Following information were collected for each of the clinical trials obtained
      from the search; number of centres (single center/multicentric), type of the
      institution undertaking the research (government/private/combined), study
      (observational/interventional), study design (randomized/single blinded/double
      blinded), type of health condition, type of participants (healthy/patients),
      sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4),
      publication details (published/not published), whether it was a postgraduate
      thesis or not and prospective or retrospective registration of clinical trials,
      methodological quality (method of randomization, allocation concealment).
      Descriptive statistics was used for analysis of various categories. Trend
      analysis was done to assess the changes over a period of time. RESULTS: The
      search yielded a total of 84 trials of which majority of them were single
      centered. Considering the study design more than half of the registered clinical
      trials were double-blinded (47/84 [56%]). With regard to the place of conducting
      a trial, most of the trials were planned to be performed in private hospitals
      (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional
      while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the
      registered clinical trials were recruiting patients while the rest were being
      done in healthy participants. From 2011, some of the postgraduate thesis trials
      had also been registered (2011-8; 2012-8; 2013-13; 2014-6). Inadequacy in
      reporting the method of randomization and allocation concealment was observed in
      37/67 (55.2%) and 31/67 (46.2%) clinical trials respectively. A considerable
      number of postgraduate theses was also registered with CTRI in dentistry and
      majority of the clinical trials despite being completed are not yet published.
      CONCLUSION: The number of clinical trials in dentistry are low in India, and more
      focus should be placed by dental investigators regarding the reporting standards.
      Furthermore, researchers and trial sponsors should aim at publication of the
      research findings so that it is made publically available for use. A clear-cut
      need exists for an increase in both the quantity and quality of clinical trials
      in dentistry.

PMID- 28447022
TI  - Common pitfalls in statistical analysis: Linear regression analysis.
AB  - In a previous article in this series, we explained correlation analysis which
      describes the strength of relationship between two continuous variables. In this
      article, we deal with linear regression analysis which predicts the value of one
      continuous variable from another. We also discuss the assumptions and pitfalls
      associated with this analysis.

PMID- 28447023
TI  - Virtue ethics of clinical research.

PMID- 28447024
TI  - Following the Preclinical Data: Leveraging the Abscopal Effect More
      Efficaciously.
AB  - Radiotherapy is employed in the treatment of over 50% of cancer patients.
      However, this therapy approach is limited to mainly treating localized disease.
      In 1953, Mole described the remarkable abscopal effect, whereby, localized
      radiotherapy of a patient's primary tumor might engender regression of cancer at
      distant sites, which were not irradiated. Current consensus is that if the
      abscopal effect can be efficaciously leveraged, it would transform the field of
      radiation oncology, extending the use of radiotherapy to treatment of both
      localized and metastatic disease. A close examination of the literature on the
      abscopal effect proffers a disruptive new hypothesis for consideration in future
      clinical trials. This hypothesis is that generating a subcutaneous human tumor
      autograft as the primary tumor may be a more efficacious approach to prime the
      abscopal effect. Following the preclinical data, the merits and demerits of such
      an approach are examined in this article.

PMID- 28447026
TI  - Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss,
      and Persistence of Genetic Elements In situ of the Infant Gut.
AB  - Elucidating the adaptive strategies and plasticity of bacterial genomes in situ
      is crucial for understanding the epidemiology and evolution of pathogens
      threatening human health. While much is known about the evolution of Escherichia
      coli in controlled laboratory environments, less effort has been made to
      elucidate the genome dynamics of E. coli in its native settings. Here, we follow
      the genome dynamics of co-existing E. coli lineages in situ of the infant gut
      during the first year of life. One E. coli lineage causes a urinary tract
      infection (UTI) and experiences several alterations of its genomic content during
      subsequent antibiotic treatment. Interestingly, all isolates of this
      uropathogenic E. coli strain carried a highly stable plasmid implicated in
      virulence of diverse pathogenic strains from all over the world. While virulence
      elements are certainly beneficial during infection scenarios, their role in gut
      colonization and pathogen persistence is poorly understood. We performed in vivo
      competitive fitness experiments to assess the role of this highly disseminated
      virulence plasmid in gut colonization, but found no evidence for a direct benefit
      of plasmid carriage. Through plasmid stability assays, we demonstrate that this
      plasmid is maintained in a parasitic manner, by strong first-line inheritance
      mechanisms, acting on the single-cell level, rather than providing a direct
      survival advantage in the gut. Investigating the ecology of endemic accessory
      genetic elements, in their pathogenic hosts and native environment, is of vital
      importance if we want to understand the evolution and persistence of highly
      virulent and drug resistant bacterial isolates.

PMID- 28447027
TI  - Gastric Function in Children with Oesophageal Atresia and Tracheoesophageal
      Fistula.
AB  - Oesophageal atresia and tracheoesophageal fistula (OA-TOF) are a multifaceted
      condition which affects patients throughout their lives. Even though it is one of
      the most common gastrointestinal malformations, most of the current studies focus
      on gastro-oesophageal reflux disease, anastomotic strictures, and feeding
      difficulties. However, there is increasing evidence that a proportion of patients
      with OA-TOF also have abnormal gastric function. This review aims to provide a
      comprehensive understanding of studies of gastric function in patients with OA
      TOF. The etiology of this abnormality has been hypothesized to be congenital
      and/or acquired. Several modalities are currently available for the investigation
      of gastric function, each of them trying to answer specific clinical questions.
      This review summarizes the studies that have looked at gastric function in the OA
      TOF cohort with gastric emptying studies (gastric emptying scintigraphy and 13C
      octanoic breath test), gastric manometry, electrogastrography, and oral glucose
      tolerance test. However, these modalities are limited due to poor age-specific
      normative values and heterogeneous methodologies used. The evaluation of symptoms
      in this cohort is crucial, modalities for abnormal gastric function are also
      described. With appropriate investigations and symptoms questionnaires, treatment
      strategies can be implemented to correct abnormal gastric function and thereby
      improve the outcomes and quality of life of patients with OA-TOF. This review
      highlights the need for large international multicentre collaborative studies and
      high-quality prospective randomized controlled trials to improve our
      understanding of gastric function in this cohort.

PMID- 28447028
TI  - Flipping Classrooms in a School of Public Health.
AB  - Alternative course formats are gaining increasing attention in higher education.
      The literature provides a number of examples and studies of flipped classrooms in
      the medical sciences and liberal arts and sciences. However, fewer than five
      papers on flipped classes in graduate public health courses have been published,
      and none in health management. Because graduate public health education is
      competency based, it seems that a flipped approach with its applied nature would
      be an appropriate form of teaching public health courses. This paper describes
      three successfully flipped courses taught in a school of public health. We
      provide a rationale for flipping, description of each course, and lessons
      learned. Once some of the challenges are overcome, we believe flipping courses
      can provide an alternative approach that enhances active learning in applied,
      public health, and health management courses.

PMID- 28447029
TI  - Cornell Alliance for Science Evaluation of Consensus on Genetically Modified Food
      Safety: Weaknesses in Study Design.
AB  - Cornell Alliance for Science has launched an initiative in which "citizen
      scientists" are called upon to evaluate studies on health risks of genetically
      modified (GM) crops and foods. The purpose is to establish whether the consensus
      on GM food safety claimed by the American Association for the Advancement of
      Science (AAAS) is supported by a review of the scientific literature. The
      Alliance's citizen scientists are examining more than 12,000 publication
      abstracts to quantify how far the scientific literature supports the AAAS's
      statement. We identify a number of fundamental weaknesses in the Alliance's study
      design, including evaluation is based only on information provided in the
      publication abstract; there is a lack of clarity as to what material is included
      in the 12,000 study abstracts to be reviewed, since the number of appropriately
      designed investigations addressing GM food safety are few; there is uncertainty
      as to whether studies of toxic effects arising from GM crop-associated pesticides
      will be included; there is a lack of clarity regarding whether divergent yet
      equally valid interpretations of the same study will be taken into account; and
      there is no definition of the cutoff point for consensus or non-consensus on GM
      food safety. In addition, vital industry proprietary biosafety data on GM crops
      and associated pesticides are not publicly available and is thus cannot inform
      this project. Based on these weaknesses in the study design, we believe it is
      questionable as to whether any objective or meaningful conclusion can be drawn
      from the Alliance's initiative.

PMID- 28447025
TI  - Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications
      for Therapy.
AB  - The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising
      fibroblasts, cells of the immune system, and endothelial cells, besides various
      soluble secretory factors from all cellular components (including tumor cells).
      The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming
      of the metabolism occurs in tumor and non-tumor cells that underlies the nature
      of interactions as well as competitions ensuring steady supply of nutrients and
      anapleoretic molecules for the tumor cells that fuels its growth even under
      hypoxic conditions. This metabolic reprogramming also plays a significant role in
      suppressing the immune attack on the tumor cells and in resistance to therapies.
      Thus, the metabolic cooperation and competition among the different TME
      components besides the inherent alterations in the tumor cells arising out of
      genetic as well as epigenetic changes supports growth, metastasis, and
      therapeutic resistance. This review focuses on the metabolic remodeling achieved
      through an active cooperation and competition among the three principal
      components of the TME-the tumor cells, the T cells, and the cancer-associated
      fibroblasts while discussing about the current strategies that target metabolism
      of TME components. Further, we will also consider the probable therapeutic
      opportunities targeting the various metabolic pathways as well as the signaling
      molecules/transcription factors regulating them for the development of novel
      treatment strategies for cancer.

PMID- 28447031
TI  - Microfluidic Concentric Gradient Generator Design for High-Throughput Cell-Based
      Studies.
AB  - Gradients of diffusible signaling molecules play important role in various
      processes, ranging from cell differentiation to toxicological evaluation.
      Microfluidic technology provides an accurate control of tempospatial conditions.
      However, current microfluidic platforms are not designed to handle multiple
      gradients and cell populations simultaneously. Here, we demonstrate a rapidly
      adaptable microfluidic design able to expose multiple cell populations to an
      array of chemical gradients. Our design is based on pressure-equilibrated
      concentric channels and a pressure-dissipating control layer, facilitating the
      seeding of multiple cell populations in a single device. The design was
      numerically evaluated and experimentally validated. The device consists of 8
      radiating stimuli channels and 12 circular cell culture channels, creating an
      array of 96 different continuous gradients that can be simultaneously monitored
      over time.

PMID- 28447030
TI  - Screening and Optimizing Antimicrobial Peptides by Using SPOT-Synthesis.
AB  - Peptide arrays on cellulose are a powerful tool to investigate peptide
      interactions with a number of different molecules, for examples antibodies,
      receptors or enzymes. Such peptide arrays can also be used to study interactions
      with whole cells. In this review, we focus on the interaction of small
      antimicrobial peptides with bacteria. Antimicrobial peptides (AMPs) can kill
      multidrug-resistant (MDR) human pathogenic bacteria and therefore could be next
      generation antibiotics targeting MDR bacteria. We describe the screen and the
      result of different optimization strategies of peptides cleaved from the
      membrane. In addition, screening of antibacterial activity of peptides that are
      tethered to the surface is discussed. Surface-active peptides can be used to
      protect surfaces from bacterial infections, for example implants.

PMID- 28447032
TI  - Risk of Sleepiness-Related Accidents in Switzerland: Results of an Online Sleep
      Apnea Risk Questionnaire and Awareness Campaigns.
AB  - OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is associated with major
      morbidity and mortality but OSAS is frequently under recognized. To promote
      awareness of OSAS, the Swiss Lung League launched an online questionnaire
      combined with annual advertisements in mass media. Characteristics of
      participants, prevalence of sleep apnea, OSAS-related symptoms, and their
      association with accidents were investigated. METHODS: A questionnaire was
      created incorporating anthropometrics, the Epworth sleepiness scale (ESS), the
      OSAS domain of the sleep disorders questionnaire (SDQ), and a question on
      accidents related to sleepiness. RESULTS: A total of 198,422 persons
      participated, 63% were male, mean (+/-SD) age was 45 (+/-16) years, weight 80 (+/
      18) kg, height 173 (+/-9) cm, and body mass index 26.7 (+/-5.4) kg/m2. Some male
      (19%) and female (17%) participants had both elevated ESS and SAS scores (SAS >
      35 (m)/SAS > 31 (f) and ESS > 10) and were suspected of having sleep apnea. In
      all, 6,654 (3.4%) had suffered an accident related to sleepiness. In multivariate
      regression analysis, ESS item #8 (falling asleep on the wheel, while stopping for
      a few minutes in traffic) was closest related to suffering an accident (OR 2.8).
      CONCLUSION: The OSAS awareness campaign of the Swiss Lung League reached a large
      number of people of both genders and of a wide age range. Many participants
      suffered from excessive sleepiness and symptoms of sleep apnea were highly
      prevalent. The campaign raised awareness of OSAS and contributed to the diagnosis
      and treatment of sleep apnea, thereby possibly preventing related morbidity and
      mortality.

PMID- 28447033
TI  - Prokineticin Is a New Linker between Obesity and Cardiovascular Diseases.
AB  - Obesity is a fast growing epidemic event worldwide. Fatness is associated with a
      number of comorbidities, including cardiovascular diseases (CVDs). Although
      obesity can be heredity in 30-70% cases, the environmental contributions also
      play an important role in the increasing prevalence of obesity. The relationship
      between development of obesity and CVD is poorly characterized. Obesity and CVD
      can also be resulted from a common mechanism such as metabolic, inflammatory, and
      neurohormonal changes. Prokineticins are defined as cytokines (immunoregulatory
      proteins), adipokines (adipocyte-secreted hormone), angiogenic (increasing vessel
      formation), or aneroxic (lowering food intake) hormones. Prokineticin-mediated
      signaling plays a key role in the development of obesity and CVD. Two forms of
      prokineticins exist in circulation and in various tissues including the brain,
      heart, kidney, and adipose. Prokineticins act on the two G protein-coupled
      receptors, namely, PKR1 and PKR2. Prokineticin-2 (PK2) via PKR1 receptor controls
      food intake and prevents adipose tissue expansion. The anti-adipocyte effect of
      PKR1 signaling is due to suppression of preadipocyte proliferation and
      differentiation capacity into adipocytes. PK2/PKR1 signaling promotes
      transcapillary passages of insulin and increases insulin sensitivity. It also
      plays an important role in the heart and kidney development and functions. Here,
      we discuss PK2 as a new adipocytokine in the association between obesity and CVD.
      We also highlight targeting PKR1 can be a new approach to treat obesity and CVD.

PMID- 28447034
TI  - The biomarkers of leukemia stem cells in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease characterized by
      morphology and chromosome aberrations with high mortality. Leukemia stem cells
      (LSCs) in AML played important roles in leukemia initiation, progression, and
      were considered to be the root of chemotherapeutic drug resistance and disease
      relapse. The identification and targeting LSCs depended on membrane markers like
      CD34, CD38, CD123, TIM3, CD25, CD32 and CD96. In addition, the transcription
      factors were also therapeutic targets in eradicating LSCs, such as histone
      deacetylases (HDACs), NF-kappaB, HIF-1alpha and beta-catenin. Besides membrane
      markers and transcription factors, intracellular reactive oxygen species (ROS),
      telomerase and microRNAs were identified to be new targets for ablating LSCs in
      AML.

PMID- 28447035
TI  - Novel therapeutic approaches: Rett syndrome and human induced pluripotent stem
      cell technology.
AB  - Recent advances in induced pluripotent stem cell (iPSC) technology target
      screening and discovering of therapeutic agents for the possible cure of human
      diseases. Human induced pluripotent stem cells (hiPSC) are the right kind of
      platform for testing potency of specific active compounds. Ayurveda, the Indian
      traditional system of medicine developed between 2,500 and 500 BC, is a science
      involving the intelligent formulations of herbs and minerals. It can serve as a
      "goldmine" for novel neuroprotective agents used for centuries to treat
      neurological disorders. This review discusses limitations in screening drugs for
      neurological disorders and the advantages offered by hiPSC integrated with Indian
      traditional system of medicine. We begin by describing the current state of hiPSC
      technology in research on Rett syndrome (RTT) followed by the current
      controversies in RTT research combined with the emergence of patient-specific
      hiPSC that indicate an urgent need for researchers to understand the etiology and
      drug mechanism. We conclude by offering recommendations to reinforce the
      screening of active compounds present in the ayurvedic medicines using the human
      induced pluripotent neural model system for research involving drug discovery for
      RTT. This integrative approach will fill the current knowledge gap in the
      traditional medicines and drug discovery.

PMID- 28447036
TI  - Recent translational research into targeted therapy for liposarcoma.
AB  - Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating
      from adipocytes. Treatment for LPS typically involves surgical resection and
      radiation therapy, while the use of conventional cytotoxic chemotherapy for
      unresectable or metastatic LPS remains controversial. This review summarizes the
      results of recent translational research and trials of novel therapies targeting
      various genetic and molecular aberrations in different subtypes of LPS. Genetic
      aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4,
      TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the
      fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and
      represent potential therapeutic candidates. Tyrosine kinase inhibitors targeting
      MET, AXL, IGF1R, EGFR, VEGFR2, PDGFR-beta and Aurora kinase are effective in
      certain types of LPS. Abnormalities in the PI3K/Akt signaling pathway
      deregulation of C/EBP-alpha and its partner PPAR-gamma, and the interaction
      between calreticulin (CRT) and CD47 are also promising therapeutic targets. These
      promising new approaches may help to supplement existing treatments for LPS.

PMID- 28447037
TI  - Leptomeninges: a novel stem cell niche with neurogenic potential.

PMID- 28447038
TI  - Dermal white adipose tissue renewal is regulated by the PDGFA/AKT axis.

PMID- 28447039
TI  - Discovery of a new role for the p53 family in the onset of mesendodermal
      differentiation of embryonic stem cells.

PMID- 28447040
TI  - Fetal hematopoietic stem cells are making waves.

PMID- 28447041
TI  - Role of "osteogenic" cardiac fibroblasts in pathological heart calcification.

PMID- 28447042
TI  - Memories of an X-chromosome.

PMID- 28447043
TI  - Comparative genomics of human stem cell factor (SCF).
AB  - Stem cell factor (SCF) is a critical protein with key roles in the cell such as
      hematopoiesis, gametogenesis and melanogenesis. In the present study a
      comparative analysis on nucleotide sequences of SCF was performed in Humanoids
      using bioinformatics tools including NCBI-BLAST, MEGA6, and JBrowse. Our analysis
      of nucleotide sequences to find closely evolved organisms with high similarity by
      NCBI-BLAST tools and MEGA6 showed that human and Chimpanzee (Pan troglodytes)
      were placed into the same cluster. By using JBrowse, we found that SCF in
      Neanderthal had a single copy number similar to modern human and partly conserved
      nucleotide sequences. Together, the results approved the gene flow and genetics
      similarity of SCF among human and P. troglodytes. This may suggest that during
      evolution, SCF gene transferred partly intact either on the basis of sequence or
      function from the same ancestors to P. troglodytes, the ancient human like
      Neanderthal, and then to the modern human.

PMID- 28447044
TI  - Molecular and phylogenetic characterization of Thelohanellus boggoti Qadri, 1962
      (Cnidaria, Myxosporea, Bivalvulida) infecting the fin of Indian minor carp Labeo
      dero (Hamilton, 1822).
AB  - A myxozoan parasite belonging to the genus Thelohanellus Kudo, 1933 (Cnidaria,
      Myxosporea, Bivalvulida) was isolated from the fins of Labeo dero inhabiting
      Ranjit Sagar Wetland, Punjab, India. The plasmodium was 0.5-0.7 mm in diameter
      each containing 80- 100 number of myxospores. Myxospores were egg shaped to
      ovoidal in valvular view having bluntly pointed anterior and broad rounded
      posterior end measuring 8.36x 4.77 um. Polar capsule was single, broadly pyriform
      in shape, measuring 4.77x3.98 um in size containing a polar filament coiled
      perpendicular to the longitudinal axis of myxospore body making 7-9 turns. Blast
      analysis of 18S rDNA sequence of the isolate demonstrated 98% homogeneity with
      Thelohanellus sp. (KU155561, Unpublished), followed by 91% with T. caudatus
      (KM252684) and Thelohanellus sp. FCO (KR819273). The intensity of infection was
      recorded to be light as indicated by fin plasmodial index (FPI = 1). In the
      present study, T. boggoti has been described using 18S rRNA gene and phylogenetic
      analysis using MEGA.6.

PMID- 28447045
TI  - Association of VNTR polymorphism of tumor necrosis factor receptor 2 (TNFRSF1B)
      with pulmonary tuberculosis.
AB  - This study was designed to find out the impact of the variable number of tandem
      repeats (VNTR) of the tumor necrosis factor receptor 2 (TNFRSF1B) on pulmonary
      tuberculosis (PTB) risk in an Iranian population. This case-control study was
      done on 159 PTB patients and 158 healthy subjects. Bi-allelic TNFRSF1B VNTR was
      genotyped by polymerase chain reaction. Logistic regression analysis revealed no
      significant association between TNFRSF1B VNTR and PTB risk (P>0.05). Our findings
      proposed that TNFRSF1B VNTR polymorphism is unlikely to confer susceptibility to
      PTB.

PMID- 28447046
TI  - Genetic diversity analysis of Morchella sp.by RAPD.
AB  - This study investigated the genetic diversity of morchella species using randomly
      amplified polymorphic DNA markers. Morchella species are an important group of
      edible mushrooms belonging to the family Helveliaceae with medicinal and
      economical significance. In this study we have developed an efficient method of
      genomic DNA isolation which was amplified by eight RAPD primers to test the
      polymorphism in three species of morchella. Out of all eight primers tested in
      current study, one of them (B8) resulted 100% polymorphism among the three
      studied species. Based on the RAPD profile a similarity matrix was generated to
      construct a dendrogram for phylogenetic analysis revealing the relationship among
      the three species of morchella.

PMID- 28447047
TI  - Replacement of threonine-55 with glycine decreases the reduction rate of OsTrx20
      by glutathione.
AB  - Thioredoxins (Trxs) are small ubiquitous oxidoreductase proteins with two redox
      active Cys residues in a conserved active site (WCG/PPC) that regulate numerous
      target proteins via thiol/disulfide exchanges in the cells of prokaryotes and
      eukaryotes. The isoforms OsTrx23 with a typical active site (WCGPC) and OsTrx20
      with an atypical active site (WCTPC) are two Trx h- type isoforms in rice that
      were previously found to be reduced by NADPH-dependent thioredoxin reductase and
      GSH/Grx system, respectively. In the present work the reduction of mutants
      G41TOsTrx23, T55GOsTrx20, K48DOsTrx20 and T55G-K48D OsTrx20 as well as wild types
      OsTrx23 and OsTrx20 were tested in the reaction containing either NADPH/NTR or
      glutathione (GSH). The results revealed that reduction rate of T55GOsTrx20 was
      remarkably decreased by GSH as compared to WtOsTrx20 highlighting the critical
      role of Thr-55 in interaction of OsTrx20 with GSH. On the other hand a
      significant decrease in the reduction rate of G41TOsTrx23 was observed in
      reaction containing NADPH-dependent thioredoxin reductase as compared with
      readuction rate of WtOsTrx23. These results suggest that first residue after N
      terminal active site Cys is one of the critical residue in determination of
      system that Trxs can be reduced in.

PMID- 28447048
TI  - ACE I/D and MMP-7 A-181G variants and the risk of end stage renal disease.
AB  - The variants of angiotensin converting enzyme (ACE) and matrix metalloproteinases
      (MMPs) genes might be involved in the pathogenesis of end stage renal disease
      (ESRD) and hypertension. We studied the ACE insertion/deletion (I/D) and MMP-7 A
      181G variants in 99 unrelated ESRD patients and 117 individuals without renal
      complications from Western Iran with Kurdish ethnic background. The frequency of
      ACE I/D variants was not significantly different between ESRD patients and
      controls. However, the presence of ACE D allele increased the risk of
      hypertension in ESRD patients by 2.14-fold (P=0.036). The MMP-7 -181 AG genotype
      increased the risk of ESRD by 2.04 times (P=0.026). The present study indicated
      the absence of an association between the ACE I/D polymorphism with the risk of
      ESRD. However, the ACE D allele increased the risk of hypertension in ESRD
      patients. Also, the present study suggests a role for MMP-7 AG genotype in the
      pathogenesis of ESRD.

PMID- 28447049
TI  - Surgical anatomy of gastric lymphatic drainage.
AB  - The lymphatic system of the stomach is a multidirectional and complex network
      composed of lymphatic nodes and vessels. Lymph node metastasis is the most
      important prognostic factor in curable gastric cancer and lymph node dissection
      is one of the main areas of surgical research in gastric cancer. Therefore the
      anatomical classification and embryological development of the gastric lymphatic
      system have been well described in the literature. The current description of the
      gastric lymphatic system of the stomach has a surgical orientation and follows
      the recommendations of the Japanese Gastric Cancer Association. A thorough
      knowledge of the lymphatic system surrounding the stomach proves to be invaluable
      to surgeons treating patients with gastric cancer. The aim of this paper is to
      provide a concise review about surgical anatomy of the gastric lymphatic
      drainage.

PMID- 28447050
TI  - Prognostic impact of nodal status and therapeutic implications.
AB  - The prognostic impact of lymph node (LN) metastases in gastric cancer is
      generally accepted. In primarily resected patients the pN-category and LN ratio
      are independent prognostic factors. Number of involved LNs, number of resected
      LNs, lymphangiosis and micrometastases also influence the prognosis
      significantly. To guarantee a proper D2 lymphadenectomy (LAD) at least 25 LNs
      according to the German S3 guidelines for the treatment of gastric cancer should
      be removed. Also in neoadjuvantly treated patients the ypN-category and LN ratio
      play an important prognostic role, despite the fact that UICC staging system was
      development based only on primarily resected patients. The role of response of
      LNs in neoadjuvantly treated patients is still unclear and needs further
      investigation. It seems to be less important than the response of the primary
      tumor. Limited data exists, suggesting that preoperative treatment might reduce
      the number of LNs involved and improve ypN-category. Due to further development
      in gastric cancer like laparoscopic resection and effective perioperative
      treatment in locally advanced tumor the role and the prognostic impact of LAD is
      again in the focus of discussion.

PMID- 28447051
TI  - Regorafenib in gastric cancer.

PMID- 28447052
TI  - What is the optimal colorectal cancer screening program for an average-risk
      population?

PMID- 28447053
TI  - Deciphering the pathophysiology of irritable bowel syndrome and functional
      gastrointestinal disorders-an alternative model for pathogenesis: cytokine
      controlled transepithelial multi-feedback loop.
AB  - A working theoretical model for irritable bowel syndrome (IBS) and other
      functional gastrointestinal disorders (FGIDs) does not exist, hampered by the
      lack of any clear cut invention that address all symptom and signs of the
      disease. Reports of cessation of symptom and signs of both major types of IBS
      have been published using a non-systemic, topically active agent-high potency
      polymerized cross-linked sucralfate (HPPCLS). The unique clinical effect of this
      non-systemic agent restricted to the luminal surface of the gut provides
      opportunity to elaborate on an alternative working model for the pathogenesis of
      IBS and FGIDs. While the chemical determinants of HPPCLS and the mucosal lining
      contribute to the clinical effects, the sequence of events resides in the
      functional interplay among elements within the mucosa itself. The proposed model
      assumes that failure of a pre-existing genomic-controlled surveillance of the
      epithelium localized to the luminal surface triggers primary and secondary immune
      activation of inflammation intent on restoring epithelial homeostasis. Delayed
      restoration of homeostasis results in all the symptoms, signs and likely
      molecular events that characterize IBS and FGIDs.

PMID- 28447054
TI  - The necessity of colorectal cancer screening for elderly patients.

PMID- 28447055
TI  - Associating liver partition and portal vein ligation for bleeding hepatocellular
      carcinoma in HBV cirrhosis: a safety strategy.
AB  - The incidence of hepatocellular carcinoma (HCC) spontaneous tumor rupture varies
      between 3% and 26%. For resectable HCC ruptures, emergency hepatectomy or staged
      hepatectomy after transcatheter arterial embolization (TAE) are life-saving
      procedures, and efficient therapeutic methods. We report a multimodal therapy
      including TAE, associating liver partition and portal vein ligation (ALPPS) and
      immunoglobuline infusion for a huge bleeding HCC with portal vein tumor
      thrombosis (PVTT) in hepatitis B virus (HBV) cirrhosis. ALPPS first step began
      with an abdominal toilette due to the massive hemoperitoneum and a portal vein
      incision at the bifurcation of the right and left portal veins was performed. A
      freely floating left part of the thrombus was extracted from the left portal vein
      in order to restore the left portal vein. The right portal vein with complete
      thrombosis was closed. Liver partition was then performed. The second step was
      performed without complications. A HCC Edmondson grade 4 (pT3b) and a cirrhotic
      liver parenchyma were described. Postoperative ascites decompensation was treated
      and patient was discharged in postoperative day 21. The reported triple strategy
      allowed us to prolong patient live. A multimodal therapy including TAE, ALPPS and
      immunoglobuline is a good option for a life treatment in case of huge bleeding
      hepatocellular carcinoma with PVTT in HBV cirrhosis.

PMID- 28447056
TI  - Decision making, quality of life and prophylactic gastrectomy in carriers of
      pathogenic CDH1 mutations.

PMID- 28447057
TI  - Liver resection for hepatocellular carcinoma >=5 cm.
AB  - BACKGROUND: Management of hepatocellular carcinoma (HCC) larger than 5 cm is
      still debated. The aim of our study was to compare morbidity and mortality after
      the surgical resection of HCC according to the nodule size. METHODS: Since 2001,
      429 liver resections for HCC were performed in our institution. We divided the
      cohort into two groups, 88 patients in group 1 patients with HCC diameter from 5
      to 10 cm and 39 patients in group 2 with HCC diameter >=10 cm. RESULTS: In 30.7%
      of cases in the first group and in 35.9% of cases in the second group the HCC
      grew into a healthy liver. A major liver resection was performed in 36.3% of
      cases in group 1 vs. 66.6% in group 2 (P=0.001). In two cases for the first group
      and in ten cases in the second group a laparoscopic approach was performed.
      Median operative time was higher in group 2 (P=0.001). The median post-operative
      hospital stay was similar in the two groups (P=0.897). The post-operative
      morbidity was not different between the two groups (P=0.595). CONCLUSIONS: The
      tumour size does not contraindicate a surgical resection of HCC even in patient
      with HCC >=10 cm.

PMID- 28447058
TI  - Development of lymph node dissection in laparoscopic gastrectomy: safety and
      technical tips.
AB  - With the accumulation of experience in laparoscopic radical gastrectomy and the
      progress in surgical instruments, the laparoscopic technique has been widely
      applied in gastric cancer. Combining previous reports with data from our center,
      we believe that laparoscopic surgery for gastric cancer is safe and feasible, and
      its surgery-related complications have an incidence that is not higher, and
      perhaps even lower, than that of traditional laparotomy. However, the stomach has
      many anatomical levels and an abundant blood supply; additionally, laparoscopic
      surgery is relatively difficult. Therefore, understanding the normal gastric
      peripheral vascular anatomy and variation, selecting an appropriate surgical
      approach, applying programmed surgical procedures and team cooperation, and
      paying attention to the details in lymph node dissection are keys to a successful
      laparoscopic lymph node dissection in gastric cancer.

PMID- 28447059
TI  - Randomized controlled trials evaluating laparoscopic vs. open distal gastrectomy
      for gastric cancer in 2016: a trilogy finally!

PMID- 28447060
TI  - Different regimens of perioperative chemotherapy for esophagogastric and gastric
      adenocarcinoma: does a triplet therapy with taxane generate a survival benefit?

PMID- 28447061
TI  - RAINFALL before RAINBOW-an illusion or reality?

PMID- 28447062
TI  - Modified palliative biliary stenting in situs inversus totalis patient with
      carcinoma gallbladder: feasibility and technical details.
AB  - Knowledge of the anatomical variants is essential for all invasive hepatobiliary
      procedures such as endoscopy, surgery and radiologic interventions. Modification
      in standard therapeutic interventions may be required based on variant anatomy.
      We report a technical modification in a 75-year-old female with known situs
      inversus (SI) totalis with carcinoma gallbladder. Present case highlights the
      finer technical details of the modified percutaneous transhepatic biliary
      drainage (PTBD) procedure and biliary stenting in a SI patient with carcinoma
      gallbladder causing malignant biliary obstruction.

PMID- 28447063
TI  - Lymphadenectomy: how to do it?
AB  - According to the more recent European guidelines, the D2 lymphadenectomy is
      considered the standard for curative intent treatment of patients with gastric
      cancer. Although, the surgical definition of D2 dissection and its technical
      aspects had been learned from Eastern surgeons in the past decades, some
      variations in the approach to D2 lymphadenectomy by European surgeons were
      detectable in randomized clinical trials dealing with lymphadenectomy. Despite in
      more recent years an improvement in surgical quality has been reported in
      European series, some differences in the practice of D2 dissection are thought to
      persist. As, these may contribute to discrepancies in gastric cancer survival
      observed across European countries, the standardization of surgical quality is an
      urgent need to improve the outcome of gastric cancer patients in Europe. In this
      manuscript, we focus on the technical aspects of the D2 dissection both in open
      and laparoscopic gastrectomy in order to contribute to the improvement of
      surgical care of gastric cancer in the West.

PMID- 28447064
TI  - The evolving landscape of treatment for advanced gastric cancer and the role of
      anti-angiogenic therapy: implications from results of the INTEGRATE study.

PMID- 28447065
TI  - Circadian clocks, diets and aging.
AB  - Diets and feeding regimens affect many physiological systems in the organism and
      may contribute to the development or prevention of various pathologies including
      cardiovascular diseases or metabolic syndromes. Some of the dietary paradigms,
      such as calorie restriction, have many well-documented positive metabolic effects
      as well as the potential to extend longevity in different organisms. Recently,
      the circadian clocks were put forward as integral components of the calorie
      restriction mechanisms. The circadian clocks generate the circadian rhythms in
      behavior, physiology, and metabolism; circadian disruption is associated with
      reduced fitness and decreased longevity. Here we focus on recent advances in the
      interplay between the circadian clocks and dietary paradigms. We discuss how the
      regulation of the circadian clocks by feeding/nutrients and regulation of
      nutrient signaling pathways by the clocks may contribute to the beneficial
      effects of calorie restriction on metabolism and longevity, and whether the
      circadian system can be engaged for future medical applications.

PMID- 28447066
TI  - Neuronal functions of FOXO/DAF-16.
AB  - The FOXO family of transcription factors plays a conserved role in longevity and
      tissue homeostasis across species. In the mammalian nervous system, emerging
      evidence has implicated FOXOs in cognitive performance, stem cell maintenance,
      regeneration, and protection against stress. Much of what we know about neuronal
      functions of FOXO emerged from recent studies in C. elegans. Similar to mammalian
      FOXO, the worm FOXO ortholog, called DAF-16, regulates learning and memory,
      regeneration, and stress resistance in neurons. Here, we discuss the current
      state of our knowledge of FOXO's functions in neurons in mammals and
      invertebrates, and highlight areas where our understanding is limited. Defining
      the function of FOXO factors in the healthy, aged, and diseased brain may have
      important implications for improving healthspan and treating neurodegenerative
      disease.

PMID- 28447068
TI  - MicroRNA 21 is up-regulated in adipose tissue of obese diabetic subjects.
AB  - We investigated miR21 expression in omental (OAT) and subcutaneous adipose tissue
      (SAT) from 16 obese subjects undergoing bariatric surgery. Patients were divided
      into two age- and BMI-matched groups according to the presence of type 2 diabetes
      (T2D). miR21 was not differently expressed in OAT and SAT. However, miR21
      expression was two folds greater in adipose tissue in patients with T2D.
      Accordingly, in primary cultures of adipocytes from non diabetic overweight
      subjects, miR21 expression increased after 24-h exposure to high glucose and
      insulin. In conclusion, miR21 appears linked to insulin-resistance deterioration
      within its pathophysiologic progression from obesity to T2D.

PMID- 28447067
TI  - Dietary polyunsaturated fatty acids and their metabolites: Implications for
      diabetes pathophysiology, prevention, and treatment.

PMID- 28447069
TI  - Long-term calorie restriction in humans is not associated with indices of delayed
      immunologic aging: A descriptive study.
AB  - BACKGROUND: Delayed immunologic aging is purported to be a major mechanism
      through which calorie restriction (CR) exerts its anti-aging effects in non-human
      species. However, in non-obese humans, the effect of CR on the immune system has
      been understudied relative to its effects on the cardiometabolic system.
      OBJECTIVE: To examine whether CR is associated with delayed immunologic aging in
      non-obese humans. METHODS: We tested whether long-term CR practitioners (average
      10.03 years of CR) evidenced decreased expression of T cell immunosenescence
      markers and longer immune cell telomeres compared to gender-, race/ethnicity-,
      age-, and education-matched "healthy" Body Mass Index (BMI) and
      "overweight"/"obese" BMI groups. RESULTS: Long-term human CR practitioners had
      lower BMI (p <  0.001) and fasting glucose (p <  0.001), as expected. They showed
      similar frequencies of pre-senescent cells (CD8+CD28- T cells and CD57 and PD-1
      expressing T cells) to the comparison groups. Even after adjusting for
      covariates, including cytomegalovirus status, we observed shorter peripheral
      blood mononuclear cell telomeres in the CR group (p = 0.012) and no difference in
      granulocyte telomeres between groups (p = 0.42). CONCLUSIONS: We observed no
      clear evidence that CR as it is currently practiced in humans delays immune aging
      related to telomere length or T cell immunosenescent markers.

PMID- 28447070
TI  - Ratios of soluble and insoluble dietary fibers on satiety and energy intake in
      overweight pre- and postmenopausal women.
AB  - BACKGROUND: Fibers' properties impact different mechanisms involved in satiety
      and energy intake regulation and metabolic outcomes. OBJECTIVE: Evaluate the
      effect of fiber types and menopausal status on satiety and metabolic responses in
      overweight women. METHODS: In a randomized within-subjects design, 19
      overweight/obese women [9 premenopausal and 10 postmenopausal] consumed 3
      preloads that varied by fiber content and source: 1) 3:1 ratio of
      soluble:insoluble fiber (SF), 2) 1:3 ratio of soluble:insoluble fiber (IF), 3) no
      fiber control (NFC). Subjective satiety, cholecystokinin (CCK), glucose, insulin,
      and triglyceride (TG) were measured for 3 h post-preload followed by in-lab ad
      libitum test meal and 32 hour food intake monitoring. RESULTS: Significant
      preload, time and preload by menopausal status interaction was apparent for
      hunger and fullness (p < 0.05 for both) with SF preload predominantly more
      satiating in postmenopausal women. CCK and insulin were significantly lower after
      SF preload (p < 0.0001 for both). Post-preload glucose responses differed by
      menopausal status: postmenopausal women distinguished between fiber types unlike
      premenopausal women (p = 0.02). TG was significantly elevated after the IF
      preload compared to NFC and SF (p = 0.007 and p = 0.008, respectively).
      CONCLUSIONS:Customized/personalized dietary recommendations for women during
      their premenopausal and postmenopausal years can help maximize metabolic and
      appetite control.

PMID- 28447071
TI  - The effects of reduced rpd3 levels on fly physiology.
AB  - BACKGROUND: Rpd3 is a conserved histone deacetylase that removes acetyl groups
      from lysine residues within histones and other proteins. Reduction or inhibition
      of Rpd3 extends longevity in yeast, worms, and flies. Previous studies in flies
      suggest an overlap with the mechanism of lifespan extension by dietary
      restriction. However, the mechanism of rpd3's effects on longevity remains
      unclear. OBJECTIVES: In this study we investigated how rpd3 reduction affects fly
      spontaneous physical activity, fecundity, and stress resistance. METHODS: We
      examined the effects of rpd3 reduction on fly spontaneous physical activity by
      using population monitors, we determined female fecundity by counting daily egg
      laying, and we determined fly survivorship in response to starvation and
      paraquat. RESULTS: In flies, rpd3 reduction increases peak spontaneous physical
      activity of rpd3 def male flies at a young age but does not affect total 24 hour
      activity. Male and female rpd3 def mutants are more resistant to starvation on
      low and high calorie diets. In addition, increased resistance to paraquat was
      observed in females of one allele. A decrease in rpd3 levels does not affect
      female fecundity. CONCLUSIONS: A decrease in rpd3 levels mirrors some but not all
      changes associated with calorie restriction, illustrated by an increased peak of
      spontaneous activity in rpd3 def /+ heterozygous male flies but no effect on
      total spontaneous activity and fecundity.

PMID- 28447073
TI  - Clinical Trials Corner.

PMID- 28447072
TI  - A randomized trial of the effects of the no-carrageenan diet on ulcerative
      colitis disease activity.
AB  - BACKGROUND: Carrageenan is a very common food additive in Western diets, but
      predictably causes inflammation in thousands of cell-based and animal
      experiments. OBJECTIVE: To assess the impact of carrageenan exposure on the
      interval to relapse in patients with ulcerative colitis in remission. METHODS: A
      randomized, double-blind, placebo-controlled, multicenter, clinical trial was
      conducted to assess if patients with ulcerative colitis in remission would have a
      longer interval to relapse if they followed a diet with no carrageenan. All
      participants were instructed in the no-carrageenan diet and were randomized to
      either placebo capsules or carrageenan-containing capsules. The carrageenan in
      the capsules was less than the average daily carrageenan intake from the diet.
      Relapse was defined as an increase of two or more points on the Simple Clinical
      Colitis Activity Index (SCCAI) and intensification of treatment for ulcerative
      colitis. Participants were followed by telephone calls every two weeks until
      relapse or one year of participation. The occurrence of relapse and inflammatory
      biomarkers were compared between the two groups. RESULTS: Twelve patients
      completed study questionnaires. Three patients who received carrageenan
      containing capsules relapsed, and none of the patients who received placebo
      containing capsules relapsed (p = 0.046, log-rank test). Laboratory tests showed
      increases in Interleukin-6 (p = 0.02, paired t-test, two-tailed) and fecal
      calprotectin (p = 0.06; paired t-test, two-tailed) between the beginning and the
      end of study participation in the carrageenan-exposed group, but not in the
      placebo-group. CONCLUSION: Carrageenan intake contributed to earlier relapse in
      patients with ulcerative colitis in remission. Restriction of dietary carrageenan
      may benefit patients with ulcerative colitis.

PMID- 28447074
TI  - Chidamide tablets: HDAC inhibition to treat lymphoma.
AB  - Chidamide is the first oral subtype-selective histone deacetylase inhibitor
      (HDACI) approved in China as well as the first HDACI of the benzamide class
      approved for the treatment of relapsed and refractory peripheral T-cell lymphoma
      (PTCL). This review addresses detailed information regarding chidamide, including
      the mechanism of action, preclinical pharmacology, pharmacokinetics and
      metabolism, clinical studies and application, safety, drug interactions and
      ongoing clinical trials. Although twice-weekly chidamide monotherapy has been
      recommended based on the evidence from preclinical and clinical studies with
      tolerable toxicities, its clinical efficacy could be further increased by
      combination with multidrug chemotherapy or chemo-free regimens. Further
      investigations into the mechanism of chidamide will facilitate the identification
      of optimal combined therapy approaches and suitable treatment populations. This
      review will contribute to a comprehensive understanding and better use of
      chidamide in clinical practice.

PMID- 28447075
TI  - Sofosbuvir/velpatasvir fixed-dose combination for the treatment of chronic
      hepatitis C virus infection.
AB  - The fixed-dose combination of sofosbuvir, a nucleotide analogue NS5B polymerase
      inhibitor, and velpatasvir, a second-generation NS5A inhibitor, has been approved
      by the United States Food and Drug Administration and the European Medicines
      Agency for the treatment of adult patients with chronic hepatitis C virus (HCV)
      genotype 1, 2, 3, 4, 5 or 6 infection. This combination, administered over 12
      weeks as a single-tablet regimen, has resulted in high cure rates in all 6 HCV
      genotypes and in a variety of patient populations, including patients without
      cirrhosis, patients with compensated cirrhosis and patients with HIV coinfection.
      In patients with decompensated cirrhosis, high cure rates were also achieved over
      12 weeks with sofosbuvir/velpatasvir plus ribavirin. Patients who had failed
      prior treatment with an NS5A-containing regimen were able to achieve high cure
      rates following 24 weeks of treatment with sofosbuvir/velpatasvir plus ribavirin.
      Sofosbuvir/velpatasvir was well tolerated, the most common adverse events being
      headache, fatigue and nausea.

PMID- 28447076
TI  - Promising cardiovascular and blood pressure effects of the SGLT2 inhibitors: a
      new class of antidiabetic drugs.
AB  - Patients with type 2 diabetes mellitus (T2DM) exhibit an increased risk of
      cardiovascular (CV) events. Treatment of these patients with traditional as well
      as newer glucose-lowering drugs has not demonstrated superiority in CV outcomes
      compared to placebo, despite effective control of diabetes. However, the recently
      FDA-approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment
      of T2DM have demonstrated promising CV-protecting and blood pressure-lowering
      effects in addition to their effectiveness in glucose lowering, making them a
      novel class of drugs for the treatment of T2DM. So far, there are three SGLT2
      inhibitors approved by the FDA and EMA for the treatment of T2DM: canagliflozin,
      dapagliflozin and empagliflozin. They exert their antihyperglycemic effect
      through inhibition of SGLT2 in the kidney and significantly reduce glucose
      reabsorption from the proximal renal tubule. By blocking glucose reabsorption,
      they lead to loss of calories, weight, abdominal and total body fat, blood
      pressure and CV complications. One CV outcomes randomized trial and several short
      term studies have shown reductions in CV events and blood pressure in patients
      with T2DM. It is the hope that large ongoing long-term outcome studies will
      provide further much-needed information, when they are completed.

PMID- 28447077
TI  - Evidence Europe 2017. London, UK - February 22-23, 2017.
AB  - As the political backdrop changes in both the U.S. and Europe, volatility in the
      pharma industry is beginning to be felt as the sector becomes sensitive to the
      uncertainty. U.S. President Trump has stated he will pursue an agenda against
      high U.S. drug prices and is expected to seek to repeal the Affordable Care Act,
      while in Europe, Brexit casts further unknowns in regulatory authorization
      procedures, trade and external reference pricing. With these factors in mind,
      Terrapin's Evidence Europe meeting provided for a very topical discussion on the
      use of evidence to define and communicate value in healthcare. With a particular
      focus on real-world evidence, the conference used presentations, panel briefings
      and roundtable discussions to foster debate on the challenges faced by industry
      as it negotiates the current fragile environment.

PMID- 28447078
TI  - Controllable nanothorns on TiO2 mesocrystals for efficient charge separation in
      hydrogen evolution.
AB  - Herein, we investigated that sheet-like TiO2 mesocrystals with controllable
      nanothorns on the {101} facet during the topotactic transformation exhibit facet
      induced charge separation and anisotropic electron flow, realizing the superior
      facet-dependent photocatalysis in solar energy conversion.

PMID- 28447079
TI  - Electrosynthesis of NiPx nanospheres for electrocatalytic hydrogen evolution from
      a neutral aqueous solution.
AB  - Due to the "ligand effect" and "ensemble effect", incorporating phosphorus into
      nickel metal is a promising strategy to prepare an electrocatalyst for the
      hydrogen evolution reaction (HER). Herein, uniform NiPx nanospheres are deposited
      on electrode substrates by a simple and fast electrosynthesis method. As
      expected, the NiPx nanospheres can act as an excellent HER catalyst in a neutral
      buffer solution. It requires a low overpotential of 230 mV to achieve a current
      density of 10 mA cm-2, and the stability has been proven to be outstanding by
      long-term electrolysis.

PMID- 28447080
TI  - Doping of nematic cyanobiphenyl liquid crystals with mesogen-hybridized magnetic
      nanoparticles.
AB  - Magnetic nanoparticles (MNPs) functionalized with (pro-)mesogenic ligands are
      implemented into a nematic liquid crystal (LC) and studied regarding both
      colloidal stability and magneto-optical behavior. In this study, the particle
      surface is specifically engineered to tune the MNP interactions with the LC host.
      For this purpose, four types of (pro-)mesogenic ligands (ML) are synthesized,
      which are composed of three structural parts, i.e., a rigid, LC motif (i.e.,
      cyanobiphenyl) and a functional group for nanoparticle binding, both linked via a
      flexible spacer of different alkyl chain lengths. Electrostatically stabilized
      CoFe2O4 and gamma-Fe2O3 nanoparticles with narrow size distribution and sizes
      below 3 nm are obtained via co-precipitation and subsequently functionalized to
      yield MNP@ML nanoparticles. Studies on the behaviour of the MNP@ML nanoparticles
      in the commercial LC host (i.e., 4-pentyl-4'-cyanobiphenyl (5CB)) in the bulk and
      in thin films in LC test cells, reveal the initial formation of some
      heterogeneities after transition from the isotropic to the nematic phase.
      Homogenous MNP@ML-5CB hybrids with long-term, colloidal stability, however, are
      obtained after magnetic separation of initially formed particle aggregates. In
      particular, MLs with carboxy groups and high structural flexibility (i.e., long
      linker lengths) are shown to be well suited to form stable MNP colloids, allowing
      for high MNP doping levels. As compared to undoped 5CB, the CoFe2O4@MLx-5CB
      hybrids show an increased sensitivity to the magnetic field, affecting the
      Freedericksz transition. The strongest effect, however, is observed in magnetic
      and electric fields. The coupling of the ultrasmall, spherical MNPs with the LC
      director in the magnetic field suggests the formation of LC-induced, anisometric
      MNP clusters.

PMID- 28447081
TI  - Plasma treatment effect on polymer buried interfacial structure and property.
AB  - Adhesion is important in many industrial applications including those in the
      microelectronics industry. Flip-chip assemblies commonly utilize epoxy underfills
      to promote reliability and the buried interfacial structure of underfills is
      crucial to device lifetime. Poor adhesion at this interface can cause premature
      device failure. One method to increase adhesion strength is to plasma treat the
      substrate attached to underfills, however, the mechanism of this increase in
      adhesion strength has not been thoroughly investigated at the molecular level in
      situ, because it is difficult to probe a buried interface where the adhesion
      occurs. In this work, sum frequency generation (SFG) vibrational spectroscopy was
      utilized to investigate the buried polymer/epoxy resin interface at the molecular
      level. Plasma treatment was performed on the polymer surfaces and the effects
      were examined. The buried interfaces between the polymer surface before and after
      plasma treatment and epoxy were then investigated to understand if the effects of
      the treatment can be observed using SFG. It was found that the molecular
      structure of the buried interface of the pristine polymer surface in contact with
      epoxy is drastically different from the buried interface of the plasma treated
      surface with epoxy. The buried interface containing the plasma treated polymer
      surface was found to be considerably more disordered and had much higher adhesion
      strength. This research elucidates the plasma treatment effects on structures and
      properties of buried polymer/epoxy interfaces, providing in-depth understanding
      on the mechanism of adhesion strength increase facilitated by plasma treatment.

PMID- 28447083
TI  - Rapid generation of HNO induced by visible light.
AB  - We present a new method for controlled generation of HNO, based on the
      combination of a pH photoactuator induced by visible light with an HNO donor
      activated by pH increase. This method avoids the use of UV light, and in the
      future could be extended by using an IR photoactuator.

PMID- 28447082
TI  - Temperature dependency of aqueous biphasic systems: an alternative approach for
      exploring the differences between Coulombic-dominated salts and ionic liquids.
AB  - Herein we propose an alternative way to distinguish ionic liquids from Coulombic
      dominated salts, based not on their upper limit melting temperature (100  degrees
      C), but on the trend of their phase-forming abilities to create aqueous biphasic
      systems as a function of temperature, in which a wider plethora of interactions
      can be appraised.

PMID- 28447084
TI  - One-pot formation of hydrazide macrocycles with modified cavities: an example of
      pH-sensitive unimolecular cation channels.
AB  - A series of pH-sensitive, cation-selective hydrazide macrocyclic channels have
      been synthesized. The macrocyclic channels bear multiple carboxyls in the inner
      cavity, which have a significant impact on their membrane-incorporation ability
      and NH4+ transport activity. Moreover, the K+/Cl- selectivities of the
      macrocyclic channels can be tuned by the pH value of the electrolyte.

PMID- 28447085
TI  - Studying structure and dynamics of self-assembled peptide nanostructures using
      fluorescence and super resolution microscopy.
AB  - Understanding the formation and properties of self-assembled peptide
      nanostructures is the basis for the design of new architectures for various
      applications. Here we show the potential of fluorescence and super resolution
      imaging to unveil the structural and dynamic features of peptide nanofibers with
      high spatiotemporal resolution.

PMID- 28447087
TI  - On exo-cyclic aromaticity.
AB  - The domain of aromaticity spans a wide range of molecules, from polycyclic
      aromatic hydrocarbons, heterocycles to all-metal systems. Here, in silico we
      demonstrate the aromaticity in C2B2F4, extending beyond the limit of conventional
      aromatic molecules. This molecule gains the magic number of six pi-electrons
      through an unusual electronic contribution from exo-cyclic atoms. The stability
      of the molecule is established through density functional theory, ab initio
      calculations as well as molecular dynamics simulation.

PMID- 28447086
TI  - Ultrasound neuro-modulation chip: activation of sensory neurons in Caenorhabditis
      elegans by surface acoustic waves.
AB  - Ultrasound neuro-modulation has gained increasing attention as a non-invasive
      method. In this paper, we present an ultrasound neuro-modulation chip, capable of
      initiating reversal behaviour and activating neurons of C. elegans under the
      stimulation of a single-shot, short-pulsed ultrasound. About 85.29% +/- 6.17% of
      worms respond to the ultrasound stimulation exhibiting reversal behaviour.
      Furthermore, the worms can adapt to the ultrasound stimulation with a lower
      acoustic pulse duration of stimulation. In vivo calcium imaging shows that the
      activity of ASH, a polymodal sensory neuron in C. elegans, can be directly evoked
      by the ultrasound stimulation. On the other hand, AFD, a thermal sensitive
      neuron, cannot be activated by the ultrasound stimulation using the same
      parameter and the temperature elevation during the stimulation process is
      relatively small. Consistent with the calcium imaging results, the tax-4 mutants,
      which are insensitive to temperature increase, do not show a significant
      difference in avoidance probability compared to the wild type. Therefore, the
      mechanical effects induced by ultrasound are the main reason for neural and
      behavioural modulation of C. elegans. With the advantages of confined acoustic
      energy on the surface, compatible with standard calcium imaging, this neuro
      modulation chip could be a powerful tool for revealing the molecular mechanisms
      of ultrasound neuro-modulation.

PMID- 28447088
TI  - Determination of the diffusion coefficient of hydrogen ion in hydrogels.
AB  - The role of diffusion in chemical pattern formation has been widely studied due
      to the great diversity of patterns emerging in reaction-diffusion systems,
      particularly in H+-autocatalytic reactions where hydrogels are applied to avoid
      convection. A custom-made conductometric cell is designed to measure the
      effective diffusion coefficient of a pair of strong electrolytes containing
      sodium ions or hydrogen ions with a common anion. This together with the
      individual diffusion coefficient for sodium ions, obtained from PFGSE-NMR
      spectroscopy, allows the determination of the diffusion coefficient of hydrogen
      ions in hydrogels. Numerical calculations are also performed to study the
      behavior of a diffusion-migration model describing ionic diffusion in our system.
      The method we present for one particular case may be extended for various
      hydrogels and diffusing ions (such as hydroxide) which are relevant e.g. for the
      development of pH-regulated self-healing mechanisms and hydrogels used for drug
      delivery.

PMID- 28447089
TI  - Direct access to N-unprotected tetrasubstituted propargylamines via direct
      catalytic alkynylation of N-unprotected trifluoromethyl ketimines.
AB  - Direct catalytic alkynylation of N-unprotected trifluoromethyl ketimines is
      reported for the first time. A combination of catalytic amounts of diethylzinc
      and carboxylic acids promoted the reactions under proton-transfer conditions,
      allowing an unprecedented direct access to N-unprotected alpha-tetrasubstituted
      primary amines without additional deprotection steps.

PMID- 28447090
TI  - (o-Phenyleno)naphthalene diimides: a pink fluorescent chromophore.
AB  - (o-Phenyleno)naphthalene dianhydride 7 was synthesized by a six-step reaction.
      Imidizations of 7 led to various diimides 8. Their optical and electrochemical
      properties hold promise for organic electronics.

PMID- 28447091
TI  - One-pot synthesis and properties of well-defined butadiynylene-BODIPY oligomers.
AB  - A homogeneous series of well-defined butadiynylene-BODIPY oligomers containing up
      to four BODIPY moieties have been synthesized from a "one-pot" oxidative
      homocoupling reaction of 2,6-di((trimethylsilyl)ethynyl)BODIPY. Further
      derivation of the resultant BODIPY dimer generates a water-soluble, red-emitting
      butadiyne-linked BODIPY dimer with pyridinium ions, which can ratiometrically
      detect viscosity, based on the two fluorescent conformers with the two BODIPY
      cores twisted and planar to each other depending on the viscosity of the
      environment.

PMID- 28447092
TI  - The CO dehydrogenase accessory protein CooT is a novel nickel-binding protein.
AB  - In Rhodospirillum rubrum, maturation of Carbon Monoxide Dehydrogenase (CODH)
      requires three accessory proteins, CooC, CooT and CooJ, dedicated to nickel
      insertion into the active site, which is constituted by a distorted [NiFe3S4]
      cubane coordinated with a mononuclear Fe site. CooC is an ATPase proposed to
      provide the energy required for the maturation process, while CooJ is described
      as a metallochaperone with 16 histidines and 2 cysteines at the C-terminus,
      likely involved in metal binding and/or storage. Prior to the present study, no
      information was available on CooT at the molecular level. Here, the X-ray
      structure of RrCooT was obtained, which revealed that this protein is a homodimer
      featuring a fold that resembles an Sm-like domain, suggesting a role in RNA
      metabolism that was however not supported by experimental observations.
      Biochemical and biophysical evidence based on circular dichroism spectroscopy,
      light scattering, isothermal titration calorimetry and site-directed mutagenesis
      showed that RrCooT specifically binds a single Ni(ii) per dimer, with a
      dissociation constant of 9 nM, through the pair of Cys2, highly conserved
      residues, located at the dimer interface. Despite its role in the activation of
      RrCODH in vivo, CooT was thought to be a unique protein, found only in R. rubrum,
      with an unclear function. In this study, we extended the biological impact of
      CooT, establishing that this protein is a member of a novel Ni(ii)-binding
      protein family with 111 homologues, linked to anaerobic metabolism in bacteria
      and archaea, and in most cases to the presence of CODH.

PMID- 28447093
TI  - Highly nucleophilic vitamin B12-assisted nickel-catalysed reductive coupling of
      aryl halides and non-activated alkyl tosylates.
AB  - Reductive cross-coupling of aryl halides with ubiquitous alkyl tosylates was
      developed using a combination of nickel and vitamin B12 (VB12: cyanocobalamin)
      catalysts. The tosylate was activated by reduced VB12 to form alkyl cobalt(iii),
      which served as a good alkylating agent for aryl-nickel species, leading to
      C(sp3)-C(sp2) bond formation.

PMID- 28447094
TI  - alpha,beta-Functionalization of saturated ketones with anthranils via Cu
      catalyzed sequential dehydrogenation/aza-Michael addition/annulation cascade
      reactions in one-pot.
AB  - An efficient method to access functionalized quinolines from the readily
      available saturated ketones and anthranils has been explored. This one-pot
      cascade reaction involves the in situ generation of alpha,beta-unsaturated
      ketones by the copper catalysed dehydrogenation of saturated ketones followed by
      the aza-Michael addition of anthranils and subsequent annulation.

PMID- 28447095
TI  - Investigation of the metal-insulator transition in NdNiO3 films by site-selective
      X-ray absorption spectroscopy.
AB  - In this work, multifunctional oxide NdNiO3 (NNO) thin films grown on a SrTiO3
      (STO) substrate using pulsed-laser deposition are studied. Temperature dependent
      resistivity measurements revealed that NNO/STO samples exhibit a sharp thickness
      dependent metal-insulator transition (MIT) over a range of 150-200 K. It is known
      that the electronic properties of correlated oxides are extremely complex and
      sensitive to changes in orbital occupancy. To evaluate the changes in the
      electronic and/or crystallographic structure responsible for the MIT, a site
      selective (O, Ni and Nd) X-ray absorption near edge structure (XANES) analysis is
      performed above and below the transition temperature. Analysis of XANES spectra
      suggests that: (i) in NNO films nominally trivalent Ni ions exhibit multiple
      valency (bond disproportionation), (ii) intermetallic hybridization plays an
      important role, (iii) the presence of strong O 2p-O 2p hole correlation at low
      temperature results in the opening of the p-p gap and (iv) the valency of Nd ions
      matches well with that of Nd3+. For NNO films exhibiting a sharp MIT, Ni 3d
      electron localization and concurrent existence of Ni 3d8 and Ni 3d8L[combining
      low line]2 states are responsible for the observed transition. At temperatures
      below the MIT the O 2p-O 2p hole correlation is strong enough to split the O 2p
      band stabilizing insulating phase. Temperature and thickness dependent
      differences observed in the site-selective XANES data are discussed in terms of
      possible mechanisms for the MIT (negative charge-transfer type).

PMID- 28447096
TI  - The effect of K+ cations on the phase transitions, and structural, dielectric and
      luminescence properties of [cat][K0.5Cr0.5(HCOO)3], where cat is protonated
      dimethylamine or ethylamine.
AB  - We report the synthesis, crystal structure, and dielectric, vibrational and
      emission spectra of two novel heterometallic perovskite-type metal-organic
      frameworks (MOFs) of the following formula: [(CH3)2NH2][K0.5Cr0.5(HCOO)3]
      (DMAKCr) and [C2H5NH3][K0.5Cr0.5(HCOO)3] (EtAKCr). DMAKCr crystallizes in a
      trigonal structure (R3[combining macron] space group) and undergoes an order
      disorder phase transition to the monoclinic system (P1[combining macron] space
      group) at about 190 K. The dielectric studies confirm the presence of first-order
      relaxor-like structural transformation. In the high-temperature phase, the
      dimethylammonium cations are dynamically disordered over three equal positions
      and upon cooling the dynamical disorder evolves into a two-fold one. This partial
      ordering is accompanied by a small distortion of the metal-formate framework.
      EtAKCr crystallizes in a monoclinic structure (P21/n space group) with ordered
      EtA+ cations and does not experience any phase transition. The differences in the
      thermal behavior caused by the substitution of Na+ ions by larger K+ ions in the
      [cat]MIMIII (cat = DMA+, EtA+, MI = Na+, K+ and MIII = Cr3+ and Fe3+)
      heterometallic MOF family are discussed taking into account the impact of the
      hydrogen bond (HB) pattern and other factors affecting the stability of metal
      formate frameworks. The optical studies show that DMANaCr and EtAKCr exhibit Cr3+
      based emission characteristics for intermediate ligand field strength.

PMID- 28447097
TI  - Rapid large area fabrication of multiscale through-hole membranes.
AB  - There are many proposed mechanisms by which single cells can be trapped; among
      them is the through-hole membrane for the characterization of individual
      microorganisms. Due to the small scale of the fabricated pores, the construction
      of through-hole membranes on a large scale and with relatively large areas faces
      many difficulties. This paper describes novel fabrication methods for a large
      area, freestanding micro/nano through-hole membrane constructed from versatile
      membrane materials using through-hole membranes on a microfluidic chip (THMMC).
      This process can rapidly (<20 min) fabricate membranes with high fidelity
      multiscale hole size without residual layers. The through-hole site was easily
      customizable from the micro to the nanoscale, with a low or high aspect ratio
      giving rise to reliable membranes. Also, the rigidity and biocompatibility of the
      through-hole membrane are easily tunable by simple injection of versatile
      membrane materials to obtain a large area (up to 3600 mm2). Membranes produced in
      this manner were then applied as a proof of concept for the isolation,
      cultivation, and quantification of individual micro-algal cells for selection
      with respect to the growth rate, while controlling the quorum sensing mediated
      metabolic and proliferative changes.

PMID- 28447098
TI  - Application of Natural Language Processing and Network Analysis Techniques to
      Post-market Reports for the Evaluation of Dose-related Anti-Thymocyte Globulin
      Safety Patterns.
AB  - OBJECTIVE: To evaluate the feasibility of automated dose and adverse event
      information retrieval in supporting the identification of safety patterns.
      METHODS: We extracted all rabbit Anti-Thymocyte Globulin (rATG) reports submitted
      to the United States Food and Drug Administration Adverse Event Reporting System
      (FAERS) from the product's initial licensure in April 16, 1984 through February
      8, 2016. We processed the narratives using the Medication Extraction (MedEx) and
      the Event-based Text-mining of Health Electronic Records (ETHER) systems and
      retrieved the appropriate medication, clinical, and temporal information. When
      necessary, the extracted information was manually curated. This process resulted
      in a high quality dataset that was analyzed with the Pattern-based and Advanced
      Network Analyzer for Clinical Evaluation and Assessment (PANACEA) to explore the
      association of rATG dosing with post-transplant lymphoproliferative disorder
      (PTLD). RESULTS: Although manual curation was necessary to improve the data
      quality, MedEx and ETHER supported the extraction of the appropriate information.
      We created a final dataset of 1,380 cases with complete information for rATG
      dosing and date of administration. Analysis in PANACEA found that PTLD was
      associated with cumulative doses of rATG >8 mg/kg, even in periods where most of
      the submissions to FAERS reported low doses of rATG. CONCLUSION: We demonstrated
      the feasibility of investigating a dose-related safety pattern for a particular
      product in FAERS using a set of automated tools.

PMID- 28447099
TI  - Endogenous developmental endothelial locus-1 limits ischaemia-related
      angiogenesis by blocking inflammation.
AB  - We have recently identified endothelial cell-secreted developmental endothelial
      locus-1 (Del-1) as an endogenous inhibitor of beta2-integrin-dependent leukocyte
      infiltration. Del-1 was previously also implicated in angiogenesis. Here, we
      addressed the role of endogenously produced Del-1 in ischaemia-related
      angiogenesis. Intriguingly, Del-1-deficient mice displayed increased
      neovascularisation in two independent ischaemic models (retinopathy of
      prematurity and hind-limb ischaemia), as compared to Del-1-proficient mice. On
      the contrary, angiogenic sprouting in vitro or ex vivo (aortic ring assay) and
      physiological developmental retina angiogenesis were not affected by Del-1
      deficiency. Mechanistically, the enhanced ischaemic neovascularisation in Del-1
      deficiency was linked to higher infiltration of the ischaemic tissue by CD45+
      haematopoietic and immune cells. Moreover, Del-1-deficiency promoted beta2
      integrin-dependent adhesion of haematopoietic cells to endothelial cells in
      vitro, and the homing of hematopoietic progenitor cells and of immune cell
      populations to ischaemic muscles in vivo. Consistently, the increased hind limb
      ischaemia-related angiogenesis in Del-1 deficiency was completely reversed in
      mice lacking both Del-1 and the beta2-integrin LFA-1. Additionally, enhanced
      retinopathy-associated neovascularisation in Del-1-deficient mice was reversed by
      LFA-1 blockade. Our data reveal a hitherto unrecognised function of endogenous
      Del-1 as a local inhibitor of ischaemia-induced angiogenesis by restraining LFA-1
      dependent homing of pro-angiogenic haematopoietic cells to ischaemic tissues. Our
      findings are relevant for the optimisation of therapeutic approaches in the
      context of ischaemic diseases.

PMID- 28447100
TI  - F7 gene variants modulate protein levels in a large cohort of patients with
      factor VII deficiency. Results from a genotype-phenotype study.
AB  - Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by
      mutations in F7 gene with autosomal recessive inheritance. A clinical
      heterogeneity with poor correlation with FVII:C levels has been described. It was
      the objective of this study to identify genetic defects and to evaluate their
      relationships with phenotype in a large cohort of patients with FVII:C<50 %. One
      hundred twenty-three probands were genotyped for F7 mutations and three
      polymorphic variants and classified according to recently published clinical
      scores. Forty out of 123 patients (33 %) were symptomatic (43 bleedings). A
      severe bleeding tendency was observed only in patients with FVII:C<0.10 %.
      Epistaxis (11 %) and menorrhagia (32 % of females in fertile age) were the most
      frequent bleedings. Molecular analysis detected 48 mutations, 20 not reported in
      the F7 international databases. Most mutations (62 %) were missense, large
      deletions were 6.2 %. Compound heterozygotes/homozygotes for mutations presented
      lower FVII:C levels compared to the other classes (Chi2=43.709, p<0,001). The
      polymorphisms distribution was significantly different among the three F7
      genotypic groups (Chi2=72.289, p<0,001). The presence of truncating mutations was
      associated with lowest FVII:C levels (Chi2=21.351, p=0.002). This study confirms
      the clinical and molecular variability of the disease and the type of symptoms.
      It shows a good correlation between the type of F7 mutation and/or polymorphisms
      and FVII:C levels, without a direct link between FVII:C and bleeding tendency.
      The results suggest that large deletions are underestimated and that they
      represent a common mechanism of F7 gene inactivation which should always be
      investigated in the diagnostic testing for FVII deficiency.

PMID- 28447101
TI  - Development and use of a clinical decision support tool for behavioral health
      screening in primary care clinics.
AB  - OBJECTIVE: Screening, brief intervention, and referral for treatment (SBIRT) for
      behavioral health (BH) is a key clinical process. SBIRT tools in electronic
      health records (EHR) are infrequent and rarely studied. Our goals were 1) to
      design and implement SBIRT using clinical decision support (CDS) in a commercial
      EHR; and 2) to conduct a pragmatic evaluation of the impact of the tools on
      clinical outcomes. METHODS: A multidisciplinary team designed SBIRT workflows and
      CDS tools. We analyzed the outcomes using a retrospective descriptive convenience
      cohort with age-matched comparison group. Data extracted from the EHR were
      evaluated using descriptive statistics. RESULTS: There were 2 outcomes studied:
      1) development and use of new BH screening tools and workflows; and 2) the
      results of use of those tools by a convenience sample of 866 encounters. The EHR
      tools developed included a flowsheet for documenting screens for 3 domains
      (depression, alcohol use, and prescription misuse); and 5 alerts with clinical
      recommendations based on screening; and reminders for annual screening. Positive
      screen rate was 21% (>=1 domain) with 60% of those positive for depression.
      Screening was rarely positive in 2 domains (11%), and never positive in 3
      domains. Positive and negative screens led to higher rates of documentation of
      brief intervention (BI) compared with a matched sample who did not receive
      screening, including changes in psychotropic medications, updated BH terms on the
      problem list, or referral for BH intervention. Clinical process outcomes changed
      even when screening was negative. CONCLUSIONS: Modified workflows for BH
      screening and CDS tools with clinical recommendations can be deployed in the EHR.
      Using SBIRT tools changed clinical process metrics even when screening was
      negative, perhaps due to conversations about BH not captured in the screening
      flowsheet. Although there are limitations to the study, results support ongoing
      investigation.

PMID- 28447102
TI  - Multimodal breast cancer imaging using coregistered dynamic diffuse optical
      tomography and digital breast tomosynthesis.
AB  - Diffuse optical tomography (DOT) is emerging as a noninvasive functional imaging
      method for breast cancer diagnosis and neoadjuvant chemotherapy monitoring. In
      particular, the multimodal approach of combining DOT with x-ray digital breast
      tomosynthesis (DBT) is especially synergistic as DBT prior information can be
      used to enhance the DOT reconstruction. DOT, in turn, provides a functional
      information overlay onto the mammographic images, increasing sensitivity and
      specificity to cancer pathology. We describe a dynamic DOT apparatus designed for
      tight integration with commercial DBT scanners and providing a fast (up to 1 Hz)
      image acquisition rate to enable tracking hemodynamic changes induced by the
      mammographic breast compression. The system integrates 96 continuous-wave and 24
      frequency-domain source locations as well as 32 continuous wave and 20 frequency
      domain detection locations into low-profile plastic plates that can easily mate
      to the DBT compression paddle and x-ray detector cover, respectively. We
      demonstrate system performance using static and dynamic tissue-like phantoms as
      well as in vivo images acquired from the pool of patients recalled for breast
      biopsies at the Massachusetts General Hospital Breast Imaging Division.

PMID- 28447103
TI  - Comparison of Clinical Outcomes Following Head and Neck Surgery Among Patients
      Who Contract to Abstain From Alcohol vs Patients Who Abuse Alcohol.

PMID- 28447105
TI  - Meta-analysis of hypertension and osteoporotic fracture risk in women and men.
AB  - : The present meta-analysis synthesized evidence from 10 articles encompassing 28
      independent studies to verify the association between hypertension and
      osteoporotic fracture risk in women and men. Our results indicate that the risk
      of osteoporotic fracture among individuals with hypertension was higher than that
      among individuals without hypertension. INTRODUCTION: Epidemiological studies
      have suggested that hypertension is related to osteoporotic fracture. However,
      discrepancies exist in the reported findings. In this study, a systematic review
      of relevant published articles was conducted to verify the association between
      hypertension and osteoporotic fracture risk in women and men. METHODS: PubMed
      (1953_October 5th, 2016) and Embase (1974_October 5th, 2016) were systematically
      searched for relevant articles. Odds ratios (ORs) and confidence intervals (CIs)
      were derived using random effect models. Categorical, subgroup, heterogeneity,
      publication bias, and meta-regression analyses were conducted. RESULTS: We
      analyzed 10 articles encompassing 28 independent studies, 1,430,431 participants,
      and 148,048 osteoporotic fracture cases. The risk of osteoporotic fracture among
      individuals with hypertension was higher (pooled OR = 1.33, 95% CI 1.25-1.40; I 2
      = 72.3%, P < 0.001) than that among individuals without hypertension. The
      association between hypertension and fracture risk was slightly stronger in women
      (pooled OR = 1.52, 95% CI 1.30-1.79) than in men (pooled OR = 1.35, 95% CI 1.26
      1.44). Studies conducted in Asia revealed results that were consistent with those
      of studies performed in Europe. CONCLUSIONS: Hypertension is associated with
      osteoporotic fracture risk. However, the biological mechanisms underlying the
      effect of hypertension on osteoporotic fracture remain to be elucidated.

PMID- 28447106
TI  - Defining hip fracture with claims data: outpatient and provider claims matter.
AB  - : Medicare claims are commonly used to identify hip fractures, but there is no
      universally accepted definition. We found that a definition using inpatient
      claims identified fewer fractures than a definition including outpatient and
      provider claims. Few additional fractures were identified by including
      inconsistent diagnostic and procedural codes at contiguous sites. INTRODUCTION:
      Medicare claims data is commonly used in research studies to identify hip
      fractures, but there is no universally accepted definition of fracture. Our
      purpose was to describe potential misclassification when hip fractures are
      defined using Medicare Part A (inpatient) claims without considering Part B
      (outpatient and provider) claims and when inconsistent diagnostic and procedural
      codes occur at contiguous fracture sites (e.g., femoral shaft or pelvic).
      METHODS: Participants included all long-stay nursing home residents enrolled in
      Medicare Parts A and B fee-for-service between 1/1/2008 and 12/31/2009 with
      follow-up through 12/31/2011. We compared the number of hip fractures identified
      using only Part A claims to (1) Part A plus Part B claims and (2) Part A and Part
      B claims plus discordant codes at contiguous fracture sites. RESULTS: Among
      1,257,279 long-stay residents, 40,932 (3.2%) met the definition of hip fracture
      using Part A claims, and 41,687 residents (3.3%) met the definition using Part B
      claims. 4566 hip fractures identified using Part B claims would not have been
      captured using Part A claims. An additional 227 hip fractures were identified
      after considering contiguous fracture sites. CONCLUSIONS: When ascertaining hip
      fractures, a definition using outpatient and provider claims identified 11% more
      fractures than a definition with only inpatient claims. Future studies should
      publish their definition of fracture and specify if diagnostic codes from
      contiguous fracture sites were used.

PMID- 28447104
TI  - BMP type II receptor as a therapeutic target in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a
      progressive elevation in mean pulmonary arterial pressure. This occurs due to
      abnormal remodeling of small peripheral lung vasculature resulting in progressive
      occlusion of the artery lumen that eventually causes right heart failure and
      death. The most common cause of PAH is inactivating mutations in the gene
      encoding a bone morphogenetic protein type II receptor (BMPRII). Current
      therapeutic options for PAH are limited and focused mainly on reversal of
      pulmonary vasoconstriction and proliferation of vascular cells. Although these
      treatments can relieve disease symptoms, PAH remains a progressive lethal
      disease. Emerging data suggest that restoration of BMPRII signaling in PAH is a
      promising alternative that could prevent and reverse pulmonary vascular
      remodeling. Here we will focus on recent advances in rescuing BMPRII expression,
      function or signaling to prevent and reverse pulmonary vascular remodeling in PAH
      and its feasibility for clinical translation. Furthermore, we summarize the role
      of described miRNAs that directly target the BMPR2 gene in blood vessels. We
      discuss the therapeutic potential and the limitations of promising new approaches
      to restore BMPRII signaling in PAH patients. Different mutations in BMPR2 and
      environmental/genetic factors make PAH a heterogeneous disease and it is thus
      likely that the best approach will be patient-tailored therapies.

PMID- 28447107
TI  - [Role of anesthesiology in pain medicine and palliative care treatment in German
      hospitals : Survey of department heads of anesthesiology on treatment
      structures].
AB  - BACKGROUND: The aim of this analysis was to describe the role of anesthesiology
      departments in pain medicine and palliative care services in German hospitals.
      METHOD: In the year 2012, all heads of departments of anesthesiology registered
      with the German Society of Anesthesiology and Intensive Care Medicine were
      surveyed about structures of pain medicine and palliative care services in their
      hospitals using a standardized postal questionnaire. RESULTS: Out of 408 returned
      questionnaires (response rate 47%) 403 could be evaluated. Of the hospitals 58%
      had a designated pain medicine service, in 36 (9%) of the hospitals this was
      organized as an independent department and in 195 (57%) as part of another
      department, mostly the department of anesthesiology. The "pain clinic" as an
      outpatient service was the most common form of structure for pain medicine
      services (41%). Inpatient pain medicine units were available in 77 (19%) of the
      hospitals and a partial inpatient unit in the form of a day hospital in 26 (7%)
      of the hospitals. For the care of inpatients from other departments, there was an
      intrahospital pain consultation service in 166 of the hospitals, which was the
      only structure for pain medicine in 32 of the 231 hospitals that reported having
      a designated pain medicine service. In 160 pain medicine services
      anesthesiologists were the only medical practitioners and in a further 18 both
      anesthesiologists and other specialists were available (orthopedist/orthopedic
      surgeons n = 6, internal medicine n = 4, psychiatrist n = 2, general practitioner
      = 1 and neurologist n = 1). Only two hospitals had no anesthesiologist in the
      pain medicine team and for the remaining 51 hospitals no information was
      provided. In 189 of the 231 hospitals with pain medicine services, there was at
      least 1 physician with special qualifications in pain management. In 97 (44%) of
      the hospitals psychologists were part of the team with 53 having at least 1
      psychologist with a special qualification in chronic pain management. Of the
      hospitals, 16% had a specialized department for palliative care, in 32% a
      specialized palliative care service was part of another department, which was the
      department of anesthesiology in 30%. Of the hospitals 56% had a palliative care
      consultation service, 41% had a specialized inpatient palliative care unit, 6% an
      outpatient clinic, 4% a day hospital and in 16% a specialized outpatient
      palliative care (SOPC) serving the community was incorporated. Inpatient
      consultation services and the SOPC were more common when the department of
      anesthesiology was involved in the palliative care services. CONCLUSION: In
      German hospitals, the departments of anesthesiology make a significant
      contribution to the provision of both pain medicine and palliative care services.
      Nevertheless, the respective structures of care are often incomplete or even
      lacking. There were shortcomings in terms of organization and qualification of
      the team in pain medicine services (e.g. no doctor with special qualifications in
      pain management or no psychologist). Palliative care services are more often
      organized as independent departments than as pain medicine services. Engagement
      of the anesthesiology department in palliative care is linked to a broader scope
      of the services provided, which might reflect the capacity of many
      anesthesiologists to work in an interdisciplinary manner and across interfaces.

PMID- 28447108
TI  - Split-bolus intravenous contrast material injection vs. single-bolus injection in
      patients following endovascular abdominal aortic repair (EVAR).
AB  - PURPOSE: To investigate the feasibility and accuracy of a split-bolus contrast
      injection CTA (SB-CTA) compared to a single-bolus injection CTA (SI-CTA) protocol
      of post-EVAR patients. MATERIALS AND METHODS: In this IRB-approved study,
      patients who underwent SB-CTA and SI-CTA after EVAR were evaluated. Attenuation
      and contrast-to-noise ratio (CNR) of vessels and parenchymal organs were
      assessed. Subjective enhancement of vessels, quality of 3D reconstructions, and
      enhancement phase of parenchymal organs were assessed by two independent readers.
      Endoleak visibility and incidental findings were evaluated. RESULTS: Fifty-six
      patients with SB-CTA and SI-CTA at two different time points after EVAR were
      included in the study (112 imaging studies, mean age 75 +/- 9 years). There was
      no difference in attenuation and CNR for aorta between SB-CTA and SI-CTA (310 +/-
      87 vs. 311 +/- 80 HU, p = 0.88; 31.1 +/- 12.6 vs. 29.0 +/- 12.2, p = 0.20),
      although both were improved in the venous structures and parenchymal organs with
      SB-CTA (portal vein: 149 +/- 33 vs. 88 +/- 32 HU, 11.6 +/- 5.6 vs. 4.3 +/- 3.4;
      liver: 91 +/- 19 vs. 68 +/- 20 HU, 4.4 +/- 2.8 vs. 2.1 +/- 2.0; pancreas: 108 +/-
      27 vs. 82 +/- 23 HU, 6.4 +/- 3.1 vs. 3.6 +/- 2.4; p < 0.0001). Subjectively,
      enhancement of veins, liver, spleen, bowel, and kidneys was improved (p < 0.001),
      while there was no difference for the aorta (p = 0.46) and 3D reconstructions (p
      = 0.58). None of the 18/56 (32.1%) endoleaks was missed with the SB-CTA. More
      incidental findings were detected with SB-CTA (158/56) compared to SI-CTA
      (135/56), p < 0.001. SB-CTA was able to adequately characterize 7/15 (47%) of the
      findings that needed further evaluation in SI-CTA. 4/15 (26%) incidental findings
      that were missed with SI-CTA but seen with SB-CTA required further evaluation.
      CONCLUSION: Split-bolus injection CTA in the follow-up of EVAR patients allows
      reliable visualization of endoleaks with improved subjective and objective image
      quality.

PMID- 28447109
TI  - Diagnostic nomogram for gallbladder wall thickening mimicking malignancy: using
      contrast-enhanced ultrasonography or multi-detector computed tomography?
AB  - OBJECTIVES: To establish a diagnostic nomogram using contrast-enhanced
      ultrasonography (CEUS) in gallbladder wall thickening mimicking malignancy and
      compare with multi-detector computed tomography (MDCT). METHODS: Seventy-two
      patients with gallbladder wall thickening on B-mode ultrasonography (BUS) were
      examined by CEUS to develop independent predictors for diagnosing gallbladder
      carcinoma. Among the 72 cases, 48 patients underwent both CEUS and MDCT. The
      diagnostic performances of different sets of CEUS criteria and MDCT were
      compared. A prediction model of malignancy using CEUS was developed. The
      performance of the nomogram was assessed with respect to its calibration,
      discrimination, and clinical usefulness. RESULTS: Multivariate logistic
      regression indicated that inhomogeneous enhancement in the arterial phase was the
      strongest independent predictor of malignancy (odds ratio, OR 51.162), followed
      by interrupted inner layer (OR 19.788), washout time <=40 s (OR 16.686), and wall
      thickness >1.6 cm (OR 3.019), which were all selected into the nomogram. Combined
      with the above significant features, the diagnostic performance of CEUS (AUC =
      0.917) was higher than that of MDCT (AUC = 0.788, P = 0.070). The predictive
      model using CEUS showed good discrimination, with a concordance index of 0.974
      (0.950 through internal validation), and good calibration. Decision curve
      analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: CEUS
      could accurately differentiate between malignant and benign gallbladder wall
      thickening with equivalent efficacy compared to MDCT. The proposed nomogram could
      be conveniently used to facilitate the preoperative individualized prediction of
      malignancy in patients with gallbladder wall thickening.

PMID- 28447110
TI  - [Diagnosis and therapy of benign intraarticular tumors].
AB  - Intraarticular benign tumors are rare lesions in many cases seen as incidental
      findings. One of the typical lesions is the diffuse or nodular form of pigmented
      villonodular synovitis, which needs a complete surgical removal. Magnetic
      Resonance Imaging (MRI) is diagnostic in most of the cases because of the
      intracellular iron content which shows an at least in some parts dark T2
      sequence. Adjuvant therapies as radiosynoviorthesis should be considered in
      diffuse or recurrent lesions. Synovial Chondromatosis represents a metaplastic
      disorder of the synovial membrane resulting in the production of loose cartilage
      bodies. Also in this dissease synovectomy or, in late cases, removal of the loose
      bodies only, is recommended. Synovial hemangiomas are hamartomas which may lead
      to pain or restriction of movement. In these cases total or partial resection is
      justified. Alternative treatment options such as laserablation may be possible.
      Lipoma arborescens represents a proliferative lipoid lesion of the subsynovial
      region leading to villonodular synovial proliferation. If clinically symptomatic,
      resection by arthroscopic or open synovectomy is recommented.

PMID- 28447111
TI  - [Diagnostics and treatment of osteoid osteoma].
AB  - BACKGROUND: Osteoid osteoma is the third most common benign bone tumor and
      typically induces pain that is worse at night. OBJECTIVE: To identify the
      epidemiological, pathogenetic, histological and radiological characteristics of
      osteoid osteoma and to present the broad variety of treatment options. MATERIAL
      AND METHODS: This review article summarizes relevant clinical studies and meta
      analyses on this topic. RESULTS: Osteoid osteoma is characterized by a central
      nidus smaller than 1.5 cm in diameter with surrounding bone sclerosis. In the
      majority of cases, the tumor occurs in the long bones of the lower extremities
      and is predominantly manifested in patients aged between 5 and 25 years. Pain is
      mediated by prostaglandins, which stimulate afferent peripheral nerve fibers.
      Besides plain radiographs, thin-section computed tomography represents the gold
      standard of diagnostics but should be complemented by magnetic resonance or
      nuclear medicine imaging modalities. The conservative treatment consists of long
      term therapy with non-steroidal anti-inflammatory drugs. Minimally invasive
      radiofrequency ablation of the nidus is the current operative treatment of
      choice. CONCLUSION: Success rates of radiofrequency ablation and other minimally
      invasive procedures are high while treatment costs and length of hospital stay
      are low. Thus, open surgical curettage is reserved for rare indications and en
      bloc excision of the nidus should only be performed in cases of recurrent
      lesions.

PMID- 28447112
TI  - [Imaging diagnostics of breast metastases from extramammary tumors].
AB  - Breast metastases of solid extramammary tumors are very rare in comparison to
      primary malignancies of the breast and account for only 0.33-6.3% of all
      malignant neoplasms of the breast. The most common primary tumors are malignant
      melanoma, distant sarcomas, lung cancer, ovarian cancer, renal cell cancer and
      thyroid cancer in decreasing order of frequency. This review article summarizes
      the clinical features and the different imaging findings of breast metastases
      from different extramammary solid tumors. Breast metastases are often incidental
      findings in computed tomography (CT) or positron emission tomography CT (PET-CT)
      imaging. Mammography shows two different imaging patterns, namely focal lesions
      and diffuse architectural distortion with skin thickening. Breast metastases
      presenting as focal masses usually occur as solitary and more rarely as multiple
      round lesions with a smooth edge boundary. Associated calcifications are rare
      findings. Diffuse architectural distortion with skin thickening is more common in
      breast metastases from most gastric tumors, ovarian cancer and rhabdomyosarcoma.
      Using ultrasound most lesions are hypoechoic, oval or round with smooth
      boundaries and posterior acoustic enhancement. The magnetic resonance imaging
      (MRI) criteria of breast metastases show an inconstant signal behavior that
      cannot be safely classified as benign or malignant. In summary, in patients with
      known malignancies the presence of breast metastases should be considered even
      with imposing clinically and radiologically benign findings.

PMID- 28447113
TI  - [Hans Holfelder and the SS x-ray unit].

PMID- 28447115
TI  - Human genetics as a model for target validation: finding new therapies for
      diabetes.
AB  - Type 2 diabetes is a global epidemic with major effects on healthcare expenditure
      and quality of life. Currently available treatments are inadequate for the
      prevention of comorbidities, yet progress towards new therapies remains slow. A
      major barrier is the insufficiency of traditional preclinical models for
      predicting drug efficacy and safety. Human genetics offers a complementary model
      to assess causal mechanisms for target validation. Genetic perturbations are
      'experiments of nature' that provide a uniquely relevant window into the long
      term effects of modulating specific targets. Here, we show that genetic
      discoveries over the past decades have accurately predicted (now known)
      therapeutic mechanisms for type 2 diabetes. These findings highlight the
      potential for use of human genetic variation for prospective target validation,
      and establish a framework for future applications. Studies into rare, monogenic
      forms of diabetes have also provided proof-of-principle for precision medicine,
      and the applicability of this paradigm to complex disease is discussed. Finally,
      we highlight some of the limitations that are relevant to the use of genome-wide
      association studies (GWAS) in the search for new therapies for diabetes. A key
      outstanding challenge is the translation of GWAS signals into disease biology and
      we outline possible solutions for tackling this experimental bottleneck.

PMID- 28447118
TI  - [Sun protection].

PMID- 28447116
TI  - Brain changes in overweight/obese and normal-weight adults with type 2 diabetes
      mellitus.
AB  - AIMS/HYPOTHESIS: Overweight and obesity may significantly worsen glycaemic and
      metabolic control in type 2 diabetes. However, little is known about the effects
      of overweight and obesity on the brains of people with type 2 diabetes. Here, we
      investigate whether the presence of overweight or obesity influences the brain
      and cognitive functions during early stage type 2 diabetes. METHODS: This study
      attempted to uncouple the effects of overweight/obesity from those of type 2
      diabetes on brain structures and cognition. Overweight/obese participants with
      type 2 diabetes had more severe and progressive abnormalities in their brain
      structures and cognition during early stage type 2 diabetes compared with
      participants with normal weight. Relationships between each of these measures and
      disease duration were also examined. RESULTS: Global mean cortical thickness was
      lower in the overweight/obese type 2 diabetes group than in the normal-weight
      type 2 diabetes group (z = -2.96, p for group effect = 0.003). A negative
      correlation was observed between disease duration and global mean white matter
      integrity (z = 2.42, p for interaction = 0.02) in the overweight/obese type 2
      diabetes group, but not in the normal-weight type 2 diabetes group.
      Overweight/obese individuals with type 2 diabetes showed a decrease in
      psychomotor speed performance related to disease duration (z = -2.12, p for
      interaction = 0.03), while normal-weight participants did not.
      CONCLUSIONS/INTERPRETATION: The current study attempted to uncouple the effects
      of overweight/obesity from those of type 2 diabetes on brain structures and
      cognition. Overweight/obese participants with type 2 diabetes had more severe and
      progressive abnormalities in brain structures and cognition during early stage
      type 2 diabetes compared with normal-weight participants.

PMID- 28447117
TI  - A new major-effect QTL for waterlogging tolerance in wild barley (H. spontaneum).
AB  - KEY MESSAGE: We report the first study on the unique allele from wild barley that
      can improve waterlogging tolerance in cultivated barley with a substantially
      higher contribution to aerenchyma formation. Waterlogging is one of the major
      abiotic stresses that dramatically reduce barley crop yield. Direct selection on
      waterlogging tolerance in the field is less effective due to its viability to
      environment. The most effective way of selection is to choose traits that make
      significant contributions to the overall tolerance and are easy to score.
      Aerenchyma formation under waterlogging stress is one of the most effective
      mechanisms to provide adequate oxygen supply and overcome stress-induced hypoxia
      imposed on plants. In this study, a new allele for aerenchyma formation was
      identified from a wild barley accession TAM407227 on chromosome 4H. Compared to
      that identified in cultivated barley, this allele not only produced a greater
      proportion of aerenchyma but made a greater contribution to the overall
      waterlogging tolerance. The QTL explained 76.8% of phenotypic variance in
      aerenchyma formation with a LOD value of 51.4. Markers co-segregating with the
      trait were identified and can be effectively used in marker assisted selection.

PMID- 28447119
TI  - Maxillary Sinus Lift with Beta-Tricalcium Phosphate (beta-TCP) in Edentulous
      Patients: A Nanotomographic and Raman Study.
AB  - Sinus lift elevation restores bone mass at the maxilla in edentulate patients
      before the placement of dental implants. It consists of opening the lateral side
      of the sinus and grafting beta-tricalcium phosphate granules (beta-TCP) under the
      olfactory membrane. Bone biopsies were obtained in five patients after 60 weeks.
      They were embedded undecalcified in poly(methyl methacrylate) (pMMA); blocks were
      analyzed by nanocomputed tomography (nanoCT); specific areas were studied by
      Raman microspectroscopy. Remnants of beta-TCP were osseointegrated and covered
      with mineralized bone; osteoid tissue was also filling the inner porosity.
      Macrophages having engulfed numerous beta-TCP grains were observed in marrow
      spaces. beta-TCP was identified by nanoCT as osseointegrated particles and as
      granules in the cytoplasm of macrophages. Raman microspectroscopy permitted to
      compare the spectra of beta-TCP and bone in different areas. The ratio of the
      ~820 cm-1 band of pMMA (-CH2 groups) on the nu1 phosphate band at 960 cm-1
      reflected tissue hydration because water was substituted by MMA during
      histological processing. In bone, the ratio of the ~960 cm-1 phosphate to the
      amide 1 band and the ratio nu2 phosphate band by the 1240-1250 amide III band
      reflect the mineralization degree. Specific bands of beta-TCP were found in
      osseointegrated beta-TCP granules and in the grains phagocytized by the
      macrophages. The hydration degree was maximal for beta-TCP phagocytized by
      macrophages. Raman microspectroscopy associated with nanoCT is a powerful tool in
      the analysis of the biomaterial degradation and osseointegration.

PMID- 28447120
TI  - Case Studies in Modelling, Control in Food Processes.
AB  - This chapter discusses the importance of modelling and control in increasing food
      process efficiency and ensuring product quality. Various approaches to both
      modelling and control in food processing are set in the context of the specific
      challenges in this industrial sector and latest developments in each area are
      discussed. Three industrial case studies are used to demonstrate the benefits of
      advanced measurement, modelling and control in food processes. The first case
      study illustrates the use of knowledge elicitation from expert operators in the
      process for the manufacture of potato chips (French fries) and the consequent
      improvements in process control to increase the consistency of the resulting
      product. The second case study highlights the economic benefits of tighter
      control of an important process parameter, moisture content, in potato crisp
      (chips) manufacture. The final case study describes the use of NIR spectroscopy
      in ensuring effective mixing of dry multicomponent mixtures and pastes. Practical
      implementation tips and infrastructure requirements are also discussed.

PMID- 28447121
TI  - Persistent Organic Pollutant and Hormone Levels in Harbor Porpoise with B Cell
      Lymphoma.
AB  - B-cell lymphoma, a common morphologic variant of non-Hodgkin lymphoma, has been
      associated with persistent pollutants in humans, but this association is not well
      characterized in top-level predators sharing marine resources with humans. We
      characterized and compared blubber contaminants and hormones of a pregnant harbor
      porpoise (Phocoena phocoena) with B-cell lymphoma, with those in two presumed
      healthy fishery by-caught porpoises with no lymphoma: a pregnant adult and female
      juvenile. Common historic use compounds, including polychlorinated biphenyls,
      polybrominated diphenyl ethers, and pesticides, were evaluated in blubber samples
      from three porpoises. In addition, blubber cortisol and progesterone levels
      (ng/g) were determined in all three animals. Total pollutant concentrations were
      highest in the juvenile porpoise, followed by the lymphoma porpoise and the
      nonlymphoma adult. Blubber cortisol concentrations were 191% greater in the
      pregnant with lymphoma porpoise compared with the pregnant no lymphoma porpoise,
      and 89% greater in the juvenile female compared with the pregnant no lymphoma
      porpoise. Although both adults were pregnant, progesterone levels were
      substantially greater (90%) in the healthy compared with the lymphoma adult.
      Health monitoring of top-level marine predators, such as porpoise, provides a
      sentinel measure of contaminants that serve as indicators of potential
      environmental exposure to humans.

PMID- 28447122
TI  - An overview of the role of lipid peroxidation-derived 4-hydroxynonenal in
      osteoarthritis.
AB  - BACKGROUND: Over the years, many theories have been proposed and examined to
      better explain the etiology and development of osteoarthritis (OA). The
      characteristics of joint destruction are one of the most important aspects in
      disease progression. Therefore, investigating different factors and signaling
      pathways involved in the alteration of extracellular matrix (ECM) turnover, and
      the subsequent catabolic damage to cartilage holds chief importance in
      understanding OA development. Among these factors, reactive oxygen species (ROS)
      have been at the forefront of the physiological and pathophysiological OA
      investigation. FINDINGS: In the last decades, research studies provided an
      enormous volume of data supporting the involvement of ROS in OA. Most
      interestingly, published data regarding the effect of exogenous antioxidant
      therapy in OA lack conclusive results from clinical trials to back up in vitro
      data. Accordingly, it is rational to suggest that there are other reactive
      species in OA that are not taken into account. Thus, our present review is
      focused on our current understanding of the involvement of lipid peroxidation
      derived 4-hydroxynonenal (HNE) in OA. CONCLUSION: Our findings, like those in the
      literature, illustrate the central role played by HNE in the regulation of a
      number of factors involved in joint homeostasis. HNE could thus be considered as
      an attractive therapeutic target in OA.

PMID- 28447123
TI  - Preperitoneal pelvic packing for exsanguinating pelvic fractures.
AB  - Patients with haemodynamic instability due to pelvic fracture-related bleeding
      can have life-threatening haemorrhage. Management options for haemorrhage control
      in complex pelvic fractures include bony stabilization, angioembolization, and
      preperitoneal pelvic packing (PPP). The indications for PPP as well as the
      operative technique and outcomes will be described in this review. PPP directly
      addresses the bony and venous bleeding of complex pelvic fractures, which results
      in the majority of blood loss in exsanguinating patients. As such, PPP should be
      considered for pelvic fracture patients who remain haemodynamically unstable
      despite red cell transfusion.

PMID- 28447124
TI  - History of clubfoot treatment, part I: From manipulation in antiquity to splint
      and plaster in Renaissance before tenotomy.
AB  - Idiopathic clubfoot is one of the most common problems in paediatric
      orthopaedics. The treatment is controversial and continues to be one of the
      challenges in paediatric orthopaedics. The aim of this review is to assess the
      different methods of clubfoot treatment used over the years in light of the
      documentation present in the literature and art paintings from the antiquity to
      the end of the 19th century. The aim of this paper is to review all treatment
      methods of the clubfoot over the years that were proposed to provide patients a
      functional, pain-free, normal-looking foot, with good mobility, without calluses,
      and requiring no special shoes. Hippocrates was the first to write references
      about treatment methods of clubfoot. After the Middle Ages and the Renaissance
      where patients were treated by barber-surgeons, quacks and charlatans,
      bonesetters, and trussmakers, there were more detailed studies on the disease,
      with the help of famous names in medicine such as Venel and Scarpa.

PMID- 28447126
TI  - Erratum to: Comparative lung bioavailability of fluticasone/salmeterol via a
      breath-actuated spacer and conventional plastic spacers.

PMID- 28447127
TI  - Bone adaptation of a biologically reconstructed femur after Ewing sarcoma: Long
      term morphological and densitometric evolution.
AB  - Combining bone allografts and vascularized fibular autografts in intercalary
      reconstructions after resection of bone sarcomas is of particular interest in
      young patients as it facilitates bone healing and union and helps reduce
      fractures. However, adverse events related to bone adaptation still occur. Bone
      adaptation is driven by mechanical loading, but no quantitative biomechanical
      studies exist that would help surgical planning and rehabilitation. We analyzed
      the bone adaptation of a successful femoral reconstruction after Ewing sarcoma
      during 76-month follow-up using a novel methodology that allows CT-based
      quantification of morphology and density. The results indicated that the vital
      allograft promoted bone adaptation in the reconstruction. However, an overall
      negative balance of bone remodeling and a progressive mineral density decrease in
      the femoral neck might threaten long-term bone safety. These concerns seem
      related to both surgical technique and mechanical stimuli, where a stiff metal
      implant may determine load sharing, which negatively affects bone remodeling.

PMID- 28447128
TI  - Insufficiency avulsion fracture of the femoral attachment of the posterior
      cruciate ligament of the knee joint.
AB  - Multiple ligaments are involved in avulsion injuries of the knee joint, including
      both anterior and posterior cruciate ligaments; however, avulsion injury of the
      posterior cruciate ligament is less frequently encountered than the anterior
      counterpart. Furthermore, avulsion of the femoral side of the posterior cruciate
      ligament is far less common than the tibial one.Femoral attachment avulsion
      fracture of the posterior cruciate ligaments has been reported in literature in
      adolescents, rarely in adulthood, and never before in elderly patients, showing
      an inverse relationship with advancement in patient age. The case presented here
      shows femoral attachment avulsion fracture of the posterior cruciate ligament in
      an elderly patient with secondary osteoporosis.

PMID- 28447129
TI  - Comparison between non-invasive methods used on paintings by Goya and his
      contemporaries: hyperspectral imaging vs. point-by-point spectroscopic analysis.
AB  - The development of non-invasive techniques for the characterization of pigments
      is crucial in order to preserve the integrity of the artwork. In this sense, the
      usefulness of hyperspectral imaging was demonstrated. It allows pigment
      characterization of the whole painting. However, it also sometimes requires the
      complementation of other point-by-point techniques. In the present article, the
      advantages of hyperspectral imaging over point-by-point spectroscopic analysis
      were evaluated. For that purpose, three paintings were analysed by hyperspectral
      imaging, handheld X-ray fluorescence and handheld Raman spectroscopy in order to
      determine the best non-invasive technique for pigment identifications. Thanks to
      this work, the main pigments used in Aragonese artworks, and especially in Goya's
      paintings, were identified and mapped by imaging reflection spectroscopy. All the
      analysed pigments corresponded to those used at the time of Goya. Regarding the
      techniques used, the information obtained by the hyperspectral imaging and point
      by-point analysis has been, in general, different and complementary. Given this
      fact, selecting only one technique is not recommended, and the present work
      demonstrates the usefulness of the combination of all the techniques used as the
      best non-invasive methodology for the pigments' characterization. Moreover, the
      proposed methodology is a relatively quick procedure that allows a larger number
      of Goya's paintings in the museum to be surveyed, increasing the possibility of
      obtaining significant results and providing a chance for extensive comparisons,
      which are relevant from the point of view of art history issues.

PMID- 28447131
TI  - European analytical column number 45.

PMID- 28447132
TI  - High-throughput analysis of sub-visible mAb aggregate particles using automated
      fluorescence microscopy imaging.
AB  - Aggregation of therapeutic proteins is a major concern as aggregates lower the
      yield and can impact the efficacy of the drug as well as the patient's safety. It
      can occur in all production stages; thus, it is essential to perform a detailed
      analysis for protein aggregates. Several methods such as size exclusion high
      performance liquid chromatography (SE-HPLC), light scattering, turbidity, light
      obscuration, and microscopy-based approaches are used to analyze aggregates. None
      of these methods allows determination of all types of higher molecular weight
      (HMW) species due to a limited size range. Furthermore, quantification and
      specification of different HMW species are often not possible. Moreover,
      automation is a perspective challenge coming up with automated robotic laboratory
      systems. Hence, there is a need for a fast, high-throughput-compatible method,
      which can detect a broad size range and enable quantification and classification.
      We describe a novel approach for the detection of aggregates in the size range 1
      to 1000 MUm combining fluorescent dyes for protein aggregate labelling and
      automated fluorescence microscope imaging (aFMI). After appropriate selection of
      the dye and method optimization, our method enabled us to detect various types of
      HMW species of monoclonal antibodies (mAbs). Using 10 MUmol L-1 4,4'-dianilino
      1,1'-binaphthyl-5,5'-disulfonate (Bis-ANS) in combination with aFMI allowed the
      analysis of mAb aggregates induced by different stresses occurring during
      downstream processing, storage, and administration. Validation of our results was
      performed by SE-HPLC, UV-Vis spectroscopy, and dynamic light scattering. With
      this new approach, we could not only reliably detect different HMW species but
      also quantify and classify them in an automated approach. Our method achieves
      high-throughput requirements and the selection of various fluorescent dyes
      enables a broad range of applications.

PMID- 28447133
TI  - [Digital media as laypeople's source of information about the environment and
      health].
AB  - Over the last two decades, the Internet has become the primary source of
      information. Thanks to the Internet, laypeople have access to information from
      the health and the environmental sector, which was for a long time available only
      to experts (e. g. scientific publications, statistics). Information on the
      Internet varies in quality, as generally anybody can publish online, without any
      quality control. At the same time, Internet use comes with specific situational
      characteristics. Given that the amount of information is nearly unlimited and
      that this information is easily available via search engines, users are not
      restricted to one or just a few texts, but can choose between multiple sources
      depending on their motivation and interest. Together with the heterogeneity of
      the sources, this provides the basis for a strong impact of motivation on the
      process and the outcomes of information acquisition online. Based on empirical
      research in the domain of Internet searching in the health sector, the current
      article discusses the impact of the use of digital media in the context of
      environmental medicine. Research has led to four conclusions: (1) Users are not
      sufficiently sensitive to the quality of information. (2) Information supporting
      their own opinion is preferably processed. (3) Users who feel threatened focus on
      positive information. (4) Vigilant users focus on negative information, which
      might result in cyberchrondria. The implications of these effects for the use of
      digital media in the sector of environmental medicine are discussed.

PMID- 28447134
TI  - [Poisonings in Germany : Poisons Centres, Medical Management and National
      Monitoring].
AB  - BACKGROUND: Illnesses caused by exposure to extracorporeal artificial substances
      play a major role in emergency medicine, family medicine, and environmental
      medicine. OBJECTIVE: The current situation of medical poisoning management and
      national reporting of poisonings in Germany are described. MATERIALS UND METHODS:
      The information and data presented here are derived from a literature review and
      from stakeholder interviews. RESULTS AND CONCLUSION: Eight poison centres (PCs)
      offer consultation supporting the diagnosis and treatment of poisoning cases in
      Germany today. Furthermore, those affected, their relatives and first aiders
      contact these German PCs, mainly because of a suspected poisoning. German PCs are
      also contacted by those affected and by institutions in other situations when
      expert toxicological judgement is needed, especially in cases with an
      environmental background. Often, interpretation of analytical laboratory results
      of body fluid samples or environmental samples are requested, or reference to
      environmental medicine treatment facilities is made. The PCs and the German
      Federal Institute for Risk Assessment (BfR) cooperate on the national reporting
      of the risks of poisoning for the population. In addition, the BfR collects and
      evaluates poisoning reports from German medical doctors that have been directly
      submitted. A pilot project on a national monitoring of poisonings should collate
      future case reports. An extensive and current overview of poisonings in Germany
      is a prerequisite for the identification of unsafe products and to fully comply
      with the international reporting needs of the German Federal Government in the
      case of chemical outbreaks and the resulting suspected cases.

PMID- 28447135
TI  - [Environmental medical syndromes].
AB  - Environmental medical syndromes comprise sick building syndrome (SBS), multiple
      chemical sensitivity (MCS)/idiopathic environmental intolerances (IEI),
      electromagnetic hypersensitivity, chronic fatigue syndrome (CFS), burnout,
      fibromyalgia, and the candida syndrome. There is also some overlap described in
      the literature. There is still no established knowledge of etiology, pathology,
      pathophysiology, diagnostics, therapy, prevention and prognosis. These syndromes
      are thought to result from a complex interaction of physical, chemical and/or
      (micro)biological environmental stresses, individual dispositions, psychological
      influencing factors, perceptual and processing processes, variants of
      somatization disorders, culturally or socially caused distress, or simply
      iatrogenic causation. Examination and treatment methods must be developed or
      existing ones scientifically validated. However, all uncertainties in the
      assessment of these syndromes do not absolve the physician from taking patients
      seriously and helping them as best as possible.

PMID- 28447136
TI  - [Environmental health relevance of airborne microorganisms in ambient and indoor
      air].
AB  - Airborne microorganisms occur ubiquitously in the ambient air. Besides allergic
      and irritative-toxic effects, they can cause infections after inhalation.
      Occupational studies have shown that an increased incidence of respiratory
      diseases is found in adequately exposed workers. In addition to respiratory
      diseases, severe systemic infections can also occur in particular cases, such as
      in the case of a hantavirus infection that is recognized as an occupational
      disease. In studies from environmental medicine, respiratory diseases have also
      been observed in residents living in the vicinity of livestock facilities and
      evaporative cooling towers. In the latter case, an infection risk may be caused
      by inhalation of legionella-contaminated aerosol from the exhaust air of such
      systems.Currently, there are no health-related exposure limits for airborne
      microorganisms released from such facilities. Environmental risk assessment can
      be carried out on the basis of the guideline VDI 4250 part 1, which relies on an
      excess of natural background concentration by facility-specific emissions. For
      the approval practice, the LAI-Leitfaden Bioaerosole is a uniform, standardized
      method for the determination and assessment of bioaerosol exposure.In indoor
      spaces, only a few mold types, such as Aspergillus fumigatus are able to trigger
      infections by local or systemic infection of the human organism. In particular,
      persons with an immune deficiency or allergies must be informed about the risks
      of mold exposure in indoor air. In general, mold growth in indoor spaces is a
      hygienic problem and must not be accepted as a matter of principle.

PMID- 28447137
TI  - [Climate change - physical and mental consequences].
AB  - Climate change has already had a large influence on the human environmental
      system and directly or indirectly affects physical and mental health. Triggered
      by extreme meteorological conditions, for example, storms, floods, earth slides
      and heat periods, the direct consequences range from illnesses to serious
      accidents with injuries, or in extreme cases fatalities. Indirectly, a changed
      environment due to climate change affects, amongst other things, the
      cardiovascular system and respiratory tract, and can also cause allergies and
      infectious diseases. In addition, increasing confrontation with environmental
      impacts may cause negative psychological effects such as posttraumatic stress
      disorders and anxiety, but also aggression, distress and depressive symptoms. The
      extent and severity of the health consequences depend on individual pre
      disposition, resilience, behaviour and adaptation.

PMID- 28447138
TI  - [Endocrine disruptors : Evidence from epidemiological studies necessitates a
      critical review of model systems].
AB  - Endocrine disruptive chemicals (EDCs) cause adverse health effects through
      interaction with endocrine systems. They are classified by chemical structure,
      effects on specific endocrine systems, bioaccumulation, persistence in the
      environment, or clinically observable effects. For research of the complex
      mechanisms of action in the human body, only in vitro model systems have so far
      been available, that have insufficient high-throughput capacity, which makes risk
      evaluation more difficult. In addition, in industrial nations, living people are
      often exposed to mixtures of substances, with various effects. The clinical
      importance of epigenetic changes caused by the action of EDCs during vulnerable
      phases of development is currently unclear. Epidemiological studies are
      criticized because reproducibility is not always guaranteed. Nevertheless, they
      remain the method of choice for the development and analysis of suitable model
      systems. Positive associations, in spite of sometimes conflicting results, are
      key in the selection of factors that can then be analysed in model systems in an
      unbiased way. This article depicts the mainly positive epidemiological findings
      for EDC-caused effects in the fields of growth and metabolism, neurocognitive
      development and sexual development and reproduction. As a result, there is a need
      for closer linkage between epidemiological studies and mechanistic research into
      model systems, especially focusing on the interaction of different EDCs and the
      consequences of prenatal and early life exposure.

PMID- 28447139
TI  - Early patellar dislocation can lead to tibial tubercle lateralization in rabbits.
AB  - PURPOSE: To investigate the effects of early patellar dislocation on the tibial
      tubercle location. METHODS: Sixty knees from 30 healthy 1-month-old New Zealand
      white rabbits were randomly divided into two groups of 30 knees each. Group A
      (control group) comprised the left knees, which underwent no surgical procedures.
      Group B comprised the right knees, which underwent patellar dislocation surgery.
      Computed tomography (flexion 0 degrees ) was performed preoperatively and 6
      months post-operatively. Measurements included the tibial tuberosity-trochlear
      groove distance (TT-TG) and tibial tubercle lateralization. RESULTS: No
      significant difference in the TT-TG or tibial tubercle lateralization was found
      between the two groups preoperatively. Six months post-operatively, however, the
      mean TT-TG in Group A (no patellar dislocation) and Group B (patellar
      dislocation) was 1.0 +/- 0.4 and 3.0 +/- 0.7 mm, respectively (p < 0.05). The
      mean tibial tubercle lateralization also showed a significant difference between
      Groups A and B at 6 months post-operatively (0.5 +/- 0.1 and 0.6 +/- 0.0,
      respectively; p < 0.05). CONCLUSIONS: Early patellar dislocation can lead to
      tibial tubercle lateralization and an increased TT-TG. Clinically, early
      intervention for adolescent patients with patellar dislocation will be important.
      LEVEL OF EVIDENCE: Prospective comparative study, Level II.

PMID- 28447140
TI  - Quadriceps muscle weakness is related to increased risk of radiographic knee OA
      but not its progression in both women and men: the Matsudai Knee Osteoarthritis
      Survey.
AB  - PURPOSE: The purpose of this study was to investigate the causal relationship
      between quadriceps muscle strength and radiographic knee osteoarthritis (OA) in a
      longitudinal study. METHODS: The present study included 976 knees from 488
      subjects who participated in both the 5th (2007) and 7th (2013) surveys of the
      Matsudai Knee Osteoarthritis Survey. Bilateral quadriceps strengths of each
      subject were measured using the quadriceps training machine (QTM-05F, Alcare Co.,
      Ltd., Tokyo, Japan). Additionally, weight-bearing standing knee radiographs were
      obtained, and knee OA was graded according to the Kellgren-Lawrence
      classification system. The relationships between quadriceps strength and the
      incidence and progression of radiographic knee OA were assessed using multiple
      logistic regression analysis. RESULTS: After adjusting for age and body mass
      index (BMI), both female and male knees in the lowest quantile of quadriceps
      strength had higher risk of the incidence of radiographic knee OA compared with
      the highest quantile of quadriceps strength (women: OR 2.414, 95% CI 1.098-5.311;
      men: OR 2.774, 95% CI 1.053-7.309). In contrast, after adjusting for age, BMI and
      femorotibial angle, both female and male knees in the lowest quantile compared
      with the highest quantile of quadriceps strength did not differ in risk of the
      progression of radiographic knee OA (women: OR 1.040, 95% CI 0.386-2.802; men: OR
      2.814, 95% CI 0.532-14.898). CONCLUSION: Quadriceps muscle weakness was related
      to increased risk of the incidence of radiographic knee OA, but not its
      progression, in both women and men. Therefore, the clinically important finding
      of this study is that, in both women and men, maintaining higher quadriceps
      muscle strength may be one of the most effective prevention methods for incident
      radiographic knee OA. LEVEL OF EVIDENCE: II.

PMID- 28447141
TI  - The iliotibial band and anterolateral capsule have a combined attachment to the
      Segond fracture.
AB  - The purpose of this report was to describe the injury mechanism, surgical
      findings, and outcomes in a 21-year-old professional female football player who
      presented with a complete anterior cruciate ligament (ACL) rupture and Segond
      fracture. Interview and video analysis were performed to elicit the injury
      mechanism. Clinical examination and imaging revealed a complete ACL tear, Segond
      fracture, lateral meniscus tear, MCL sprain, and posterolateral corner sprain.
      Examination under anaesthesia revealed Grade 2 pivot shift and varus/valgus
      instability. Surgical examination revealed attachment of the posterior fibres of
      the iliotibial band and the lateral capsule to the Segond fragment. The fracture
      was reduced with suture fixation, and an anatomic ACL reconstruction was
      performed. Follow-up demonstrated rotatory and anterior tibial translation
      stability, and imaging at 7 months post-operatively revealed no movement and
      continued osseous integration of the Segond fragment. Level of evidence V.

PMID- 28447142
TI  - [Quality indicators and structural requirements for Cardiac Arrest Centers-German
      Resuscitation Council (GRC)].

PMID- 28447143
TI  - [Severe accidental hypothermia : Treatment using an intravascular temperature
      management catheter].
AB  - Different techniques have been reported for the treatment of severe accidental
      hypothermia. In this case, we successfully used an intravascular catheter
      temperature management system which has been developed to induce reversible
      therapeutic hypothermia in patients following resuscitation. In our patient, the
      initial core temperature was 26.7  degrees C, and the temperature management
      system allowed for successful rewarming without complications with a maximum rate
      of about 1  degrees C/h.

PMID- 28447146
TI  - ?

PMID- 28447144
TI  - [Standardized collection of presenting complaints in the emergency room :
      Integration of coded presenting complaints into the electronic medical record
      system of an emergency department and their value for health care research].
AB  - BACKGROUND: The point of entry of a patient in emergency care is a symptom or a
      complaint. To evaluate subsequent processes in an emergency department until a
      diagnosis is made, this information has to be taken into account. OBJECTIVES: We
      report the introduction of coded presenting complaints into the electronic
      medical record system of an emergency department and describe the patients based
      on these data. METHODS: The CEDIS presenting complaint list was integrated into
      the emergency department information system of an emergency department (38,000
      patients/year). After 8 months, we performed an exploratory analysis of the most
      common presenting complaints. Furthermore, we identified the most frequent
      diagnoses for presenting complaint "shortness of breath" and the most frequent
      presenting complaints for the diagnosis of sepsis. RESULTS: After implementing
      the presenting complaint list, a presenting complaint code was assigned to each
      patient. In our sample (26,330 cases), "extremity pain and injury" comprised the
      largest group of patients (29.5%). "Chest pain-cardiac features" (3.7%) and
      "extremity weakness/symptoms of cerebrovascular accident" (2.4%) were the main
      cardiac and neurologic complaints, respectively. They were mostly triaged as
      urgent (>80%) and hospitalized in critical care units (>50%). The main diagnosis
      for presenting complaint "shortness of breath" was heart failure (25.1%), while
      the main presenting complaint for the diagnosis sepsis was "shortness of breath"
      (18.1%). CONCLUSIONS: Containing 171 presenting complaints, this classification
      was implemented successfully without providing extensive staff training. The
      documentation of coded presenting complaints enables symptom-based analysis of
      the health care provided in emergency departments.

PMID- 28447145
TI  - [Recommendations for education in ultrasound in medical intensive care and
      emergency medicine: position paper of DGIIN, DEGUM and DGK].
AB  - Point-of-care ultrasound in acute care medicine is a prerequisite for diagnosis
      and therapy monitoring of critically ill patients. There is currently no uniform
      education strategy for medical intensive care and emergency medicine. As part of
      the basic level, the trainee takes theoretical and clinical training covering
      abdominal and thoracic ultrasonography and focused cardiovascular ultrasound. In
      a second step, special knowledge and skills can be acquired at an expert level.
      This two-stage concept is intended to guarantee quality assurance in ultrasound
      education in medical intensive care and emergency medicine.

PMID- 28447147
TI  - Diffusion Kurtosis as an in vivo Imaging Marker of Early Radiation-Induced
      Changes in Radiation-Induced Temporal Lobe Necrosis in Nasopharyngeal Carcinoma
      Patients.
AB  - PURPOSE: Diffusion kurtosis imaging (DKI), an extension of the popular diffusion
      tensor imaging (DTI) model, has been applied in clinical studies of brain tissue
      changes. We explored the value of DKI for the early detection of radiation
      induced changes in temporal lobe necrosis (TLN) after radiotherapy (RT) for
      nasopharyngeal carcinoma (NPC). METHODS: A total of 400 patients with NPC were
      retrospectively enrolled; all participants underwent MRI scans 0-7 days before
      RT, at 4 weeks during RT, and 1 month after completing RT. DKI-derived kurtosis
      parameters (mean kurtosis [MK], axial kurtosis [Ka], radial kurtosis [Kr]), and
      DKI-derived diffusion parameters (fractional anisotropy [FA], mean diffusivity
      [MD], axial diffusivity [lambdaa], radial diffusivity [lambdar]) were assessed in
      temporal lobe white matter. RESULTS: Analysis was performed for 20 patients with
      temporal lobe necrosis following long-term follow-up. No brain abnormalities were
      visible on conventional MRI in any patient at 4 weeks during RT and 1 month after
      RT. Of all DKI-derived parameters, MK was significantly lower at 1 month after RT
      than before RT (P < 0.05). CONCLUSION: This study indicates DKI can detect the
      early presence of relatively subtle RT-induced brain abnormalities before TLN in
      patients with NPC and may provide a sensitive imaging technique for temporal
      white matter microstructural abnormalities that are silent on conventional
      modalities but precede TLN after RT.

PMID- 28447148
TI  - Absent pedicles in campomelic dysplasia.
AB  - OBJECTIVES: The objective of the present study is to report a case of campomelic
      dysplasia illustrating the absence of cervical and thoracic pedicles. This report
      reiterates the importance of this clinical peculiarity in the setting of spine
      instrumentation. MATERIALS AND METHODS: A 10-year-old female patient with
      campomelic dysplasia presented with progressive kyphoscoliosis and signs of
      neural compromise. Imaging studies confirmed thoracic level stenosis and
      demonstrated absence of multiple pedicles in cervical and thoracic spine. The
      patient underwent decompression and instrumentation/fusion for her spinal
      deformity. RESULTS: The patient was instrumented between C2 and L4 with pedicle
      screws and sublaminar cables. However, pedicle fixation was not possible for the
      lower cervical and upper-mid thoracic spine. Also, floating posterior elements
      precluded the use of laminar fixation in the lower cervical spine.
      Cervicothoracic lumbosacral orthosis (CTLSO) was used for external immobilization
      to supplement the tenuous fixation in the cervicothoracic area. The patient
      improved neurologically with no signs of implant failure at the 2-year follow-up.
      CONCLUSIONS: Absence of pedicles and floating posterior elements present a
      challenge during spine surgery in campomelic dysplasia. Surgeons should prepare
      for alternative fixation methods and external immobilization when planning on
      spinal instrumentation in affected patients. LEVEL OF EVIDENCE: Level IV Case
      Report.

PMID- 28447149
TI  - Erratum to: Hodgkin's lymphoma associated with paraneoplastic cerebellar
      degeneration in children: a case report and review of the literature.

PMID- 28447150
TI  - Anatomical status of the human palatopharyngeal sphincter and its functional
      implications.
AB  - PURPOSE: The transition muscle between the palatopharyngeus (PP) and the superior
      constrictor of the pharynx (SCP) encircles the pharyngeal isthmus from behind and
      is designated as the palatopharyngeal sphincter (PPS). The PPS is inferred to
      play important roles for velopharyngeal closure, but its existence remains
      controversial and its roles have been regarded as being played by the SCP. The
      present study aimed to clarify the anatomical status and functional implications
      of the PPS. MATERIALS AND METHODS: Macroscopic and microscopic examinations were
      performed on 39 and 4 cadavers, respectively. In the former, the bilateral PPSs
      and their adjacent structures were exposed from outside and/or inside. In the
      latter, the velums embedded in paraffin were cut into frontal or sagittal
      sections and alternately processed with HE and Azan stains. RESULTS: The PPS
      originated from the nasal aspect of the lateral half of the palatine aponeurosis
      and the inferior margin of the medial pterygoid plate and was distinguishable
      from the PP descending in and along the palatopharyngeal arch and the cranialmost
      portion of the SCP in its origin. It passed dorsally on the lateral side of the
      levator veli palatini and traversed around the salpingopharyngeal fold running
      longitudinally. It then entered below the SCP and ran toward the pharyngeal raphe
      with SCP muscle fibers intermingled. CONCLUSIONS: The PPS is a muscle distinct
      from the SCP. Its contraction produces Passavant's ridge and conceivably enhances
      the efficiency of velopharyngeal closure by pressing the salpingopharyngeal fold
      and the musculus uvulae ridge against the velum.

PMID- 28447152
TI  - Expression Changes in Metal-Resistance Genes in Microbacterium liquefaciens Under
      Nickel and Vanadium Exposure.
AB  - Microbacterium liquefaciens MNSH2-PHGII-2 is a nickel-vanadium-resistant
      bacterium isolated from mine tailings located in Guanajuato, Mexico. In PHGII
      liquid media, M. liquefaciens has the ability to remove 29.5 ppm of Ni and 168.3
      ppm of V. The present study reports, for the first time in M. liquefaciens, the
      presence of the genes nccA (Ni-Co-Cd resistance), hant (high-affinity nickel
      transporter), smtA, a metal-binding protein gene, and VAN2 (V resistance), which
      showed an increased expression under exposure to 200 ppm of Ni and 200 ppm of V
      during the logarithmic growth phase of the microorganism in PHGII liquid media.
      Data about the expression profile of genes conferring metal resistance to M.
      liquefaciens can improve the knowledge of those mechanisms involved in the
      processes of Ni-V resistance and probably in Ni-V removal processes. Based on our
      data, we can suggest that M. liquefaciens has the potential to be used in the
      biological treatment of toxic wastes with high Ni and V content.

PMID- 28447153
TI  - [Neurodermatitis : Atopy of the skin].
AB  - Atopic dermatitis is one of the most common skin diseases and is associated with
      an impaired quality of life due to tormenting itching and stigmatization. The
      disease almost always manifests in early childhood and exhibits specific features
      in this phase, with involvement of the extensor sides of the extremities. During
      the further course of disease, the typical flexor involvement becomes quite clear
      and a considerable proportion of patients develop the associated atopic
      respiratory diseases. Therapeutic and prophylactic measures focus on the
      prevention of trigger factors, basic skin care, and application of lipid
      replenishing creams, as well as patient and parent education. In the case of
      exacerbation, anti-inflammatory drugs are treatment of choice.

PMID- 28447154
TI  - Radiological and clinical interpretation of the patients with CSF leaks developed
      during or after endoscopic sinus surgery.
AB  - Cerebrospinal fluid (CSF) leaks associated with endoscopic sinus surgery (ESS)
      are a rare complication related to anatomical and technical factors. The
      anatomical variations at skull base level are imperative to be detected
      preoperatively by CT scan to avoid this complication. Identifying the factors
      playing a role in the incidence of the CSF leaks during and after ESS and the
      common leak sites. A retrospective review of 24 patients presented with
      incidental CSF leaks, gathered from 1999 to 2016 was performed. Images
      interpretation of the skull base area was done using four parameters includes
      Keros classification, skull base slope, fovea plane and maxillary ethmoid height
      ratio (MER). Each parameter is classified into three types according to the
      anatomical configuration, then these parameters scores categorized according to
      the level of the safety into a level I, II and III, all levels were correlated
      with each other and with the site of leakage. It was found that the major group
      presented with the level I and the least group with level III safety, with an
      evidence of the most unsafe anatomical variation was the least relevant.
      Parameters measurements revealed that the larger group of the anatomical
      variation type III was in the MER and the commonest leak site was in the
      posterior ethmoidal roof. CT scan study of the skull base is crucial in
      delineating the variations and be a roadmap to proceed safely through the
      dissection remembering that incidental CSF leaks are multifactorial in etiology.

PMID- 28447155
TI  - Fine-tuned evaluation of olfactory function in patients operated for nasal
      polyposis.
AB  - Given the forced-choice procedure of the identification test, patients with
      profound anosmia are more likely to have higher identification scores by chance
      than patients with hyposmia or normosmia. This may be a confusing factor when
      assessing the sense of smell, which alters the appreciation of real olfaction
      improvement. The aim of this study was to fine-tune the results of the
      identification Sniffin' Sticks test before and 6 weeks after surgery using the
      real identification score. A total of 133 patients underwent the Identification
      (I) and Threshold (T) tests the day before and 6 weeks after nasalization
      surgery. The scores of the identification test, called I G (global
      identification), were ranked from 0 to 16. Patients had to specify if their
      forced-choice answers were given either surely or randomly, called I H (hazard
      identification). The real score of identification I R was obtained as follow: I R
      = I G - I H. Patients with an immeasurable threshold according to the T test were
      more prone to give randomly correct answers. On the basis of I G scores, 43.6% of
      patients remained hypo-anosmic after surgery compared to 72.9% before surgery.
      Using I R scores, only 3.8% of patients remained anosmic (I R = 0) at 6 weeks
      after surgery. Hence, patients with real anosmia (I R = 0) were less prone to
      improve their olfaction than patients with I R > 0. The analysis of random factor
      when using identification test allows differentiating a real anosmia from a
      hyposmia. An I G <= 4 could be considered as a profound/real anosmia or a severe
      hyposmia. This procedure cannot, however, replace the forced-choice method in
      odor identification testing.

PMID- 28447156
TI  - [Success for a new generation of disease-modifying antirheumatic drugs : The
      Janus kinase inhibitor baricitinib in rheumatoid arthritis].

PMID- 28447157
TI  - [Sarcoidosis as a systemic disease].

PMID- 28447158
TI  - [Ultrasound diagnostics in Sjogren's syndrome].
AB  - Ultrasound of the salivary glands is a specific examination for detecting
      pathology of salivary glands in the diagnosis of Sjogren's syndrome. It is easy
      to learn, rapidly performed, non-invasive and inexpensive. Other imaging
      techniques, such as sialography and scintigraphy, are currently only rarely
      performed. For the examination, linear ultrasound probes with frequencies between
      7 and 12 MHz are recommended. Such probes are already widely available to the
      rheumatologist performing musculoskeletal ultrasound. The parotid and
      submandibular glands are bilaterally scanned both in longitudinal and transverse
      planes as a standard.Normal salivary glands have uniformly hyperechoic and
      homogeneous tissue. They can be clearly delineated from the surrounding muscles
      and soft tissue and appear similar to the thyroid gland. The salivary glands are
      typically hypoechoic and inhomogeneous in Sjogren's syndrome. Focal or diffuse
      hypoechoic or anechoic foci are found in the glands. The submandibular glands may
      become atrophic (sagittal diameter <8 mm). Particularly in disease flares, the
      parotid glands may become enlarged (sagittal diameter >20 mm). The sensitivity
      for the diagnosis is 60 to 90% and the specificity is over 90%.Doppler sonography
      does not further improve the diagnostic accuracy. Sonography has thus become an
      important tool in the diagnosis of Sjogren's syndrome.

PMID- 28447159
TI  - Catheter ablation of persistent atrial fibrillation : Beneficial effect of a
      short-term adjunctive amiodarone therapy on the long-term outcome.
AB  - BACKGROUND: Catheter ablation has become the first line therapy in patients with
      symptomatic, recurrent, drug-refractory atrial fibrillation. Circumferential
      pulmonary vein ablation is still the standard approach in these patients.
      However, the results are not very favorable (especially in patients with
      persistent atrial fibrillation). Therefore, more complex ablation strategies and
      the usefulness of (short-term) adjunctive antiarrhythmic drug therapy are a
      matter of discussion. The aim of this study was to analyze whether short-term
      amiodarone therapy after catheter ablation (3 months) has a positive effect on
      the success rates after circumferential pulmonary vein ablation in patients with
      persistent atrial fibrillation. METHODS: A total of 230 consecutive patients with
      symptomatic persistent atrial fibrillation underwent a circumferential pulmonary
      vein ablation procedure (using the NAVX or CARTO system). Catheter ablation of
      the right or left atrial isthmus and a linear lesion in the roof of the left
      atrium were only performed in selected patients with documented episodes of
      atrial fibrillation. In 115 patients, a short-term adjunctive antiarrhythmic drug
      therapy with amiodarone was initiated immediately prior to the ablation procedure
      (for the first 3 months group A). In the remaining 115 patients, no
      antiarrhythmic drug therapy was administered except for beta blockers (group B).
      RESULTS: Out of 115 patients 19 (16.5%) in group A and 34 (29.6%) in group B
      experienced an arrhythmia recurrence within the first 3 months after ablation
      requiring electrical cardioversion (P = 0.03; blanking period). One year after
      the ablation procedure 81.7% of patients in group A (94/115) and 73.0% of
      patients in group B (84/115) were free from further arrhythmia recurrences (P =
      0.16). The success rate 2 years after catheter ablation was 76.5% (no arrhythmia
      recurrence in 88/115 patients) in group A and 63.5% in group B (no arrhythmia
      recurrence in 73/115 patients; P = 0.04). There were no major complications
      during long-term follow-up. CONCLUSION: Adjunctive short-term amiodarone therapy
      improves the success rate after catheter ablation of persistent atrial
      fibrillation during long-term follow-up. This might be due to a decreased
      incidence of early arrhythmia recurrences after catheter ablation of atrial
      fibrillation and an improved reverse remodelling process.

PMID- 28447151
TI  - Rhythms in the endocrine system of fish: a review.
AB  - The environment which living organisms inhabit is not constant and many factors,
      such as light, temperature, and food availability, display cyclic and predictable
      variations. To adapt to these cyclic changes, animals present biological rhythms
      in many of their physiological variables, timing their functions to occur when
      the possibility of success is greatest. Among these variables, many endocrine
      factors have been described as displaying rhythms in vertebrates. The aim of the
      present review is to provide a thorough review of the existing knowledge on the
      rhythms of the endocrine system of fish by examining the hormones that show
      rhythmicity, how environmental factors control these rhythms and the variation in
      the responses of the endocrine system depending on the time of the day. We mainly
      focused on the hypothalamic-pituitary axis, which can be considered as the master
      axis of the endocrine system of vertebrates and regulates a great variety of
      functions, including reproduction, growth, metabolism, energy homeostasis, stress
      response, and osmoregulation. In addition, the rhythms of other hormones, such as
      melatonin and the factors, produced in the gastrointestinal system of fish are
      reviewed.

PMID- 28447160
TI  - Cancer of the ovary, fallopian tube, and peritoneum: a population-based
      comparison of the prognostic factors and outcomes.
AB  - PURPOSE: The objective was to compare the prognostic factors and outcomes among
      primary ovarian cancer (OC), fallopian tube cancer (FC), and peritoneal cancer
      (PC) patients in a population-based setting. METHODS: We analysed 5399 OC, 327
      FC, and 416 PC patients diagnosed between 1998 and 2014 in the catchment area of
      the Munich Cancer Registry (meanwhile 4.8 million inhabitants). Tumour site
      differences were examined by comparing prognostic factors, treatments, the time
      to progression, and survival. The effect of the tumour site was additionally
      analysed by a Cox regression model. RESULTS: The median age at diagnosis,
      histology, and FIGO stage significantly differed among the tumour sites (p <
      0.001); PC patients were older, more often diagnosed with a serous subtype, and
      in FIGO stage III or IV. The time to progression and survival significantly
      differed among the tumour sites. When stratified by FIGO stage, the differences
      in time to progression disappeared, and the differences in survival considerably
      weakened. The differences in the multivariate survival analysis showed an almost
      identical outcome in PC patients (HR 1.07 [0.91-1.25]) and an improved survival
      of FC patients (HR 0.63 [0.49-0.81]) compared to that of OC patients. CONCLUSION:
      The comparison of OC, FC, and PC patients in this large-scale population-based
      study showed differences in the prognostic factors. These differences primarily
      account for the inferior outcome of PC patients, and for the improved survival of
      FC compared to OC patients.

PMID- 28447161
TI  - Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes
      and cytokines.
AB  - Graft-versus-host disease (GvHD) still belongs to the major challenges after
      allogeneic hematopoietic stem cell transplantation (HSCT). Immune-suppressive
      therapy against GvHD is a double-edged sword due to risk of infections and
      relapse. The ability to adapt prophylactic treatment according to the probability
      of severe GvHD would be an essential advantage for the patients. We analyzed
      different biomarkers for their potential to predict the development of GvHD in 28
      patients who underwent allogeneic HSCT. Blood was taken once directly after
      hematopoietic engraftment. In this study, patients were monitored for 12 months
      after HSCT for the occurrence of acute GvHD or acute/chronic GvHD overlap
      syndrome. Soluble IL-2 receptor and CD4/CD8 T cell ratio were independently
      associated with the occurrence of GvHD in the observation period. However, the
      largest area under the receiver operating characteristic curve with 0.90 was
      observed when a 5-parameter biomarker score based on CD4+ T cells, CD8+ T cells,
      CD19- CD21+ precursor B cells, CD4/CD8 T cell ratio, and soluble IL-2 receptor
      was used to predict GvHD. In addition, CD8+ T cell levels above 2.3% of all
      mononuclear cells after engraftment may predict relapse-free survival at least
      for 12 months. In summary, we found a new biomarker panel for prediction of GvHD
      which is featured by established laboratory assays and high statistical
      significance. In order to introduce the biomarker panel into routine clinical
      protocols, we suggest performing a larger multi-center study.

PMID- 28447162
TI  - Cytomegalovirus retinitis in relapsed or refractory low-grade B cell lymphoma
      patients treated with bendamustine.

PMID- 28447163
TI  - Successful treatment with bendamustine and rituximab for paraneoplastic
      pemphigus.

PMID- 28447164
TI  - Glycemic Status and Prognosis of Patients with Squamous Cell Carcinoma of the
      Esophagus.
AB  - BACKGROUND: The impact of glycemic status on esophageal squamous cell carcinoma
      (ESCC) prognosis is unclear. METHODS: A total of 623 patients who underwent
      curative subtotal esophagectomy for ESCC were evaluated. Diabetes was defined as
      a prior diagnosis of diabetes under treatment or newly diagnosed diabetes based
      on preoperative glycosylated hemoglobin (HbA1c) levels. Poor glycemic control was
      defined as HbA1c >= 7.0%, whereas good glycemic control was defined as HbA1c <
      7.0%. The impact of glycemic status on long-term survival after esophagectomy was
      evaluated. RESULTS: Among the 623 patients, 64 (10.3%) had diabetes including 30
      (4.8%) with poor glycemic control. Although diabetes did not influence patient
      survival, patients with poor glycemic control had worse overall and disease
      specific survival compared with those with good glycemic control (P = 0.011 and
      0.039, respectively). Comparing poor glycemic control with good glycemic control,
      the hazard ratios (HRs) for overall and disease-specific mortality were 1.91
      (1.15-3.18) and 1.89 (1.02-3.49) in univariate analysis. After multivariate
      adjustment, poor glycemic control also had increased risk of overall and disease
      specific mortality [HR 1.72 (95% CI 1.02-2.88) and 1.65 (95% CI 0.89-3.08),
      respectively]. Poor glycemic control did not increase the risk of overall or
      disease-specific mortality in patients with stages 0-II disease but significantly
      increased this risk in those with stages III-IV disease [HR 2.05 (1.14-3.69) and
      1.95 (1.01-3.80), respectively]. CONCLUSIONS: Poor glycemic control is an
      independent risk factor for overall and disease-specific mortality after
      esophagectomy for advanced-stage ESCC.

PMID- 28447165
TI  - Esophagojejunostomy Using the Purse-String Suturing Device After Laparoscopic
      Total or Proximal Gastrectomy for Gastric Cancer.
AB  - BACKGROUND: Performing a safe esophagojejunostomy is important for the
      standardization of laparoscopic total gastrectomy. We have performed
      intracorporeal esophagojejunostomy by a circular stapler using the purse-string
      suturing device that we co-developed. The advantage of this device is that it
      makes use of the same surgical procedure as open surgery, but it does not depend
      on the surgeon's technical skills since this device does not require the
      laparoscopic hand-sewn technique. Furthermore, we have also adapted this device
      for double-tract reconstruction after laparoscopic proximal gastrectomy. In this
      study, we present the surgical procedures and postoperative short-term outcomes
      that were obtained using this novel technique. METHODS: We enrolled 94 patients
      that underwent intracorporeal esophagojejunostomy by circular stapler using our
      device after laparoscopic total or proximal gastrectomy for gastric cancer
      between November 2009 and October 2016. RESULTS: Postoperative complications
      related to esophagojejunostomy were due to anastomotic stenosis in two cases
      (2.1%) and leakage of the jejunum stump in one case (1.1%). CONCLUSIONS:
      Intracorporeal esophagojejunostomy by circular stapler using the purse-string
      suturing device is safe and feasible. This method can be one of the standard
      procedures for performing intracorporeal esophagojejunostomy.

PMID- 28447166
TI  - Treatment and outcome with traumatic lesions of the olecranon and prepatellar
      bursa: a literature review apropos a retrospective analysis including 552 cases.
AB  - BACKGROUND: Traumatic lesions of the olecranon bursa (OB) and prepatellar bursa
      (PB) are injuries commonly seen in orthopaedic trauma units. These injuries are
      associated with a high rate of complications. At present, only little is known
      about the incidence, complication rate, and treatment approaches in patients with
      acute open bursae. MATERIALS AND METHODS: A total of 552 patients who had been
      treated for acute traumatic lesions of either the olecranon bursa or the
      prepatellar bursa, or both at our department were retrospective identified in the
      years between 2009 and 2014. An analysis of the medical history of these patients
      was carried out to investigate the incidence of bursa injuries, circumstances,
      concomitant injuries, complication rate, and treatment approaches. In addition, a
      systematic literature search on PubMed was conducted. RESULTS: The incidence of
      traumatic lesions of the OB or PB in trauma patients was 0.2% (198/100,000; 62%
      OB, 38% PB). Bursectomy was performed in 83.7%. Concomitant injuries were present
      in 41% of the cases, with no significant influence on the complication rate (P =
      0.367). The overall complication rate was 19.7%. Revision surgery was necessary
      in 4.5% of the patients. No significant differences between OB and PB injuries
      were noted with regard to the complication rate (P = 0.221). There were also no
      significant differences in the complication rate between patients who received
      bursectomy and those with conservative treatment (P = 0.364). Regression analyses
      showed that prophylactic antibiotic administration significantly reduced the risk
      of infection (P = 0.04). CONCLUSIONS: Traumatic lesions of the OB and PB are
      associated with a high risk of complications. Prophylactic antibiotic therapy can
      potentially reduce the risk of infection and the need for revision surgery.

PMID- 28447167
TI  - Success rate of natural orifice specimen extraction after laparoscopic colorectal
      resections.
AB  - PURPOSE: To date, no data have been available to inform which cases are
      appropriate for natural orifice specimen extraction (NOSE) after laparoscopic
      colorectal resections (LCRRs). Our aim was to evaluate the success rate and the
      factors affecting the failure in patients who were scheduled for NOSE after
      LCRRs. METHODS: Seventy-two consecutive cases that were intended for NOSE after
      LCRR were enrolled. The transanal route was always chosen as the first option,
      and when it failed, the transvaginal route was tried in female patients. If both
      failed, the specimen was judged as unsuitable for NOSE and removed through an
      abdominal wall incision. Demographic data, surgical indications, resection
      localization, implemented procedures, incision sites, specimen extraction
      methods, specimen sizes, and failures of NOSE were recorded. RESULTS: A total of
      349 colorectal resections (240 open and 109 laparoscopic) in a 3-year period were
      examined. The subset of 72 consecutive patients who met the criteria were
      analyzed. Five cases required a conversion to open surgery during resections. In
      the remaining 67 patients, NOSE after LCRR was successful in 49 cases (73.1%) but
      failed in 18 (26.9%). Specimens were extracted from transanal and transvaginal
      routes in 37 (75.5%) and 12 (24.5%) patients, respectively. The failure rate of
      NOSE after LCRR was higher in males, in colonic lesions, and in large-sized
      tumors. The mean sizes of transanal and transvaginal extracted specimens were 3.5
      +/- 3.1 and 5.4 +/- 1.4 cm, respectively (p < 0.05). The mean size of the tumors
      in the failed cases was 6.5 +/- 4.2 cm (p < 0.05). CONCLUSIONS: Approximately 2/3
      of the unselected LCRRs were suitable for NOSE. The success rate increased with
      female gender, small-sized tumors, and rectal resections.

PMID- 28447168
TI  - Effect of carbon sources on the growth and ethanol production of native yeast
      Pichia kudriavzevii ITV-S42 isolated from sweet sorghum juice.
AB  - The importance of non-Saccharomyces yeast species in fermentation processes is
      widely acknowledged. Within this group, Pichia kudriavzevii ITV-S42 yeast strain
      shows particularly desirable characteristics for ethanol production. Despite this
      fact, a thorough study of the metabolic and kinetic characteristics of this
      strain is currently unavailable. The aim of this work is to study the nutritional
      requirements of Pichia kudriavzevii ITV-S42 strain and the effect of different
      carbon sources on the growth and ethanol production. Results showed that glucose
      and fructose were both assimilated and fermented, achieving biomass and ethanol
      yields of 0.37 and 0.32 gg-1, respectively. Glycerol was assimilated but not
      fermented; achieving a biomass yield of 0.88 gg-1. Xylose and sucrose were not
      metabolized by the yeast strain. Finally, the use of a culture medium enriched
      with salts and yeast extract favored glucose consumption both for growth and
      ethanol production, improving ethanol tolerance reported for this genre (35 g L
      1) to 90 g L-1 maximum ethanol concentration (over 100%). Furthermore Pichia
      kudriavzevii ITV-S42 maintained its fermentative capacity up to 200 g L-1 initial
      glucose, demonstrating that this yeast is osmotolerant.

PMID- 28447169
TI  - Modeling of carbon dioxide mass transfer behavior in attached cultivation
      photobioreactor using the analysis of the pH profiles.
AB  - The CO2 mass transfer model associated with growth kinetics of microalgal biofilm
      in attached cultivation photobioreactor was developed and verified by using the
      analysis of pH profiles which were in equilibrium with inorganic carbon
      components concentrations (CO2, H2CO3, HCO3- and CO32-) in medium. Model
      simulation results showed that the model well presented the biofilm growth
      process. The overall volumetric mass transfer coefficient of CO2 was more
      influenced by CO2 concentration in aerated gas but less by gas aeration rate and
      medium circulation rate. Other bio-kinetic parameters related with the microalgal
      biofilm such as CO2 diffusion coefficient in biofilm, Monod maximum utilization
      rate of CO2, lag phase duration of biofilm and half-saturation CO2 concentration
      in the biofilm were independent on operational conditions. The pH profiles
      provided a way to monitor the variations of inorganic carbon concentrations of
      medium and to regulate the cultivation of attached microalgal biofilm by CO2
      supplement.

PMID- 28447170
TI  - Surgery or stereotactic body radiotherapy for elderly stage I lung cancer? A
      propensity score matching analysis.
AB  - PURPOSE: The aim of this study was to compare the outcomes of surgery and
      stereotactic body radiotherapy (SBRT) for elderly clinical stage I non-small cell
      lung cancer (NSCLC) patients. METHODS: Patients >=80 years of age with clinical
      stage I NSCLC between August 2008 and December 2014 were treated either surgery
      or SBRT. Propensity score matching was performed to reduce bias in various
      clinicopathological factors. RESULTS: Surgery was performed in 57 cases and SBRT
      in 41 cases. In the surgery group, the operations included 34 lobectomies and 23
      sublobar resections. In the SBRT group, 27 cases were given 48 Gy in 4 fractions,
      and 14 were given 60 Gy in 10 fractions. Similar characteristics were identified
      in age (82 years), gender (male:female ratio 2:1), tumor size (2.2 cm),
      carcinoembryonic antigen (3.6 ng/ml), Charlson comorbidity index (1), Glasgow
      prognostic scale (0), and forced expiratory volume in 1 s (1.7 L) after matching.
      Before matching, the 5-year overall survival (OS) in surgery (68.3%) was
      significantly better than that in SBRT (47.4%, p = 0.02), and the 5-year disease
      specific survival (DSS) (94.1%, 78.2%, p = 0.17) was not significantly different
      between the groups. The difference in the 5-year OS became non-significant
      between the matched pairs (57.0%, 49.1%, p = 0.56). CONCLUSIONS: The outcomes of
      surgery and SBRT for elderly patients with the early stage NSCLC were roughly the
      same.

PMID- 28447171
TI  - Prevalence and clinicopathological features of H3.3 G34-mutant high-grade
      gliomas: a retrospective study of 411 consecutive glioma cases in a single
      institution.
AB  - A recurrent glycine-to-arginine/valine alteration at codon 34 (G34R/V) within
      H3F3A, a gene that encodes the replication-independent histone variant H3.3,
      reportedly occurs exclusively in pediatric glioblastomas. However, the
      clinicopathological and biological significances of this mutation have not been
      completely elucidated; especially, no such data exist for tumor samples from
      Japanese patients. We analyzed 411 consecutive glioma cases representing patients
      of all ages. Our results demonstrated that 14 patients (3.4%) harbored H3F3A
      mutations, of which four had G34R mutations and 10 had K27M mutations. G34R
      mutant tumors were located in the parietal region in two patients and the basal
      ganglia in one patient. One patient showed multi-lobular extension similar to the
      pattern observed in gliomatosis cerebri. Regarding neuroradiological features,
      intratumoral calcification was evident in two cases and all cases showed no or
      scarce contrast enhancement on MRI. Histopathologically, the four G34R-mutant
      cases included three glioblastomas and one astroblastoma. We have also
      investigated alterations in histone methylation including H3K27me3, H3K9me3, and
      H3K4me3 in G34R-mutant samples by immunohistochemistry. These results indicate
      that G34R-mutant tumors are likely to show extensive infiltration and alterations
      in global histone trimethylation might also play an important role in G34R mutant
      tumors.

PMID- 28447172
TI  - Selenium speciation in the Fountain Creek Watershed and its effects on fish
      diversity.
AB  - Se is an environmental concern as it can be toxic if present in high
      concentrations even though it is a dietary requirement for all animals. Se levels
      are a special concern in the Fountain Creek Watershed located in southeastern
      Colorado whose geological source is the Se-rich Pierre Shale. Segments of
      Fountain Creek have Se water levels that exceed the current EPA limit of 5 ug/l.
      In the studies described here, the effects of river water containing selenium
      were examined on fish populations at different sites along the Fountain Creek
      Watershed. Based on the hypothesis that high levels of Se present in the Creek
      and resident bryophytes should be an indicator of diversity in the river fish we
      explored the possibility that the low toxicity of the selenium could be due to
      speciation. A speciation analysis was conducted to determine the selenium(IV) and
      selenium(VI). Our results show that sites with higher ratios of the more toxic
      Se(IV) relative to total selenium exhibit lower fish diversity and number of
      fish. Our results indicate that factors, other than total Se, such as Se
      speciation may be involved in controlling the bioavailability and toxicity of
      this element to aquatic organisms in Fountain Creek.

PMID- 28447173
TI  - Clinical and microbiological features associated with group B Streptococcus bone
      and joint infections, France 2004-2014.
AB  - This study describes the clinical and microbiological features associated with
      group B Streptococcus (GBS) bone and joint infections (BJIs). It was a
      retrospective analysis of adult cases of GBS BJIs reported to the French National
      Reference Center for Streptococci from January 2004 to December 2014. Clinical
      data and GBS molecular characteristics are reported. Strains were collected from
      163 patients. The most frequent comorbidities were: solid organ cancer (n = 21,
      21%) and diabetes mellitus (n = 20, 20%). The main infection sites were knee
      (47/155 = 30%) and hip (43/155 = 27%), and occurred on orthopedic devices in
      71/148 cases (48%). CPS III (n = 47, 29%), Ia (n = 26, 16%) and V (n = 40, 25%)
      were predominant. Resistance to erythromycin, clindamycin and tetracycline was
      detected in 55/163 (34%), 35/163 (21%) and 132/163 (81%) strains, respectively.
      The most frequent sequence types were ST-1 (n = 21, 25%), ST-17 (n = 17, 20%) and
      ST-23 (n = 11, 13%). The rate of resistance to erythromycin was 0% for ST-17
      strains, 52% (n = 11) for ST-1 and 44% (n = 7) for ST-23 (p < 0.001). GBS bone
      and joint infections predominantly occur in patients aged >50 years and/or with
      comorbidities such as cancer and diabetes mellitus. CPS type distribution and
      MLST are very similar to that of other adult GBS invasive infections.

PMID- 28447174
TI  - Erratum to: Early diagnosis of pancreatic necrosis based on perfusion CT to
      predict the severity of acute pancreatitis.

PMID- 28447175
TI  - Present and projected future mean radiant temperature for three European cities.
AB  - Present-day and projected future changes in mean radiant temperature, T mrt in
      one northern, one mid-, and one southern European city (represented by
      Gothenburg, Frankfurt, and Porto), are presented, and the concept of hot spots is
      adopted. Air temperature, T a , increased in all cities by 2100, but changes in
      solar radiation due to changes in cloudiness counterbalanced or exacerbated the
      effects on T mrt. The number of days with high T mrt in Gothenburg was relatively
      unchanged at the end of the century (+1 day), whereas it more than doubled in
      Frankfurt and tripled in Porto. The use of street trees to reduce daytime radiant
      heat load was analyzed using hot spots to identify where trees could be most
      beneficial. Hot spots, although varying in intensity and frequency, were
      generally confined to near sunlit southeast-southwest facing walls, in northeast
      corner of courtyards, and in open spaces in all three cities. By adding trees in
      these spaces, the radiant heat load can be reduced, especially in spaces with no
      or few trees. A set of design principles for reducing the radiant heat load is
      outlined based on these findings and existing literature.

PMID- 28447176
TI  - The Structural Model of Spirituality and Psychological Well-Being for Pregnancy
      Specific Stress.
AB  - Women experience different types of stress in their lifetime. The present study
      was conducted to examine the structural model of spirituality and psychological
      well-being for pregnancy-specific stress. The present descriptive correlational
      study was conducted on 450 pregnant Iranian women (150 women from each trimester)
      in Dehdasht city in 2015. Data were collected using the personal-social
      questionnaire, the pregnancy-specific stress questionnaire, the spirituality
      questionnaire and the psychological well-being questionnaire and were then
      analyzed in SPSS-16 and Lisrel-8.8 for carrying out a path analysis. The fit
      indices of the model indicate the good fit and high compatibility of the model
      and rational relationships between the variables (GFI = 0.94, NFI = 0.85, CFI =
      0.94 and RMSEA = 0.048). Of the variables that affected pregnancy-specific stress
      through both paths, spirituality had a positive effect (B = 0.11) and the
      personal-social variable a negative effect (B = -0.37). Psychological well-being
      affected pregnancy-specific stress negatively and directly and through one path
      only (B = -0.59). The results obtained through the model confirm the effect of
      spirituality and psychological well-being in reducing pregnancy-specific stress.
      Given that handling stress has a major role in the quality of daily life in
      pregnant women, stress management skills are recommended to be promoted among
      pregnant women so as to mitigate stress and its negative consequences.

PMID- 28447177
TI  - Yeast RNA extract suppresses human osteoclast resorption in vitro.
AB  - AIMS: The aim of this short study was to test the combinations of RNA extracts
      (both the connective tissue extracts-cartilage and synovia along with yeast
      extract) found in natural ribonucleotide extract Osteochondrin S (OST) on human
      osteoclast formation and activity in vitro. METHODS: In vitro human osteoclasts
      were treated with the RNA extracts (cartilage, synovia and yeast) at
      concentrations equivalent to those in OST starting from day 7 of the culture. A
      tartrate resistant acid phosphatase stain (TRAP) was used to indicate osteoclast
      formation and activity assessed by determining area of dentine resorption.
      RESULTS: The combination of all components as is found in OST suppressed both
      osteoclast formation and activity. The yeast extract suppressed osteoclast
      activity at similar levels to that observed with all components combined.
      CONCLUSIONS: Our findings indicate that yeast RNA extracts found in OST may be
      the key component responsible for suppression of osteoclast activity.

PMID- 28447178
TI  - An MRI-Guided Telesurgery System Using a Fabry-Perot Interferometry Force Sensor
      and a Pneumatic Haptic Device.
AB  - This paper presents a surgical master-slave teleoperation system for percutaneous
      interventional procedures under continuous magnetic resonance imaging (MRI)
      guidance. The slave robot consists of a piezoelectrically actuated 6-degree-of
      freedom (DOF) robot for needle placement with an integrated fiber optic force
      sensor (1-DOF axial force measurement) using the Fabry-Perot interferometry (FPI)
      sensing principle; it is configured to operate inside the bore of the MRI scanner
      during imaging. By leveraging the advantages of pneumatic and piezoelectric
      actuation in force and position control respectively, we have designed a
      pneumatically actuated master robot (haptic device) with strain gauge based force
      sensing that is configured to operate the slave from within the scanner room
      during imaging. The slave robot follows the insertion motion of the haptic device
      while the haptic device displays the needle insertion force as measured by the
      FPI sensor. Image interference evaluation demonstrates that the telesurgery
      system presents a signal to noise ratio reduction of less than 17% and less than
      1% geometric distortion during simultaneous robot motion and imaging.
      Teleoperated needle insertion and rotation experiments were performed to reach 10
      targets in a soft tissue-mimicking phantom with 0.70 +/- 0.35 mm Cartesian space
      error.

PMID- 28447180
TI  - American Indian Knowledge, Attitudes, and Beliefs About Smokeless Tobacco: A
      Comparison of Two Focus Group Studies.
AB  - Though smokeless tobacco (SLT) use has decreased in many communities, concern for
      American Indian (AI) SLT use remains, as this population continues to be
      disproportionally affected by SLT-related diseases. Tobacco has cultural
      significance to many AI tribes, therefore tobacco cessation messages portraying
      tobacco as entirely negative may be ineffective. As a part of our formative
      research for an SLT cessation intervention, we sought to gain a better
      understanding of the knowledge, attitudes, and beliefs about SLT among AI
      community members. We describe two independent focus group studies conducted in
      Montana (ten focus groups, 54 participants) and Kansas (six focus groups, 27
      participants). Predominant themes emerged from three major topic areas (SLT use,
      program development, and recreational SLT use) during the discussions from both
      studies. The formative approach and data from these studies will allow us to more
      appropriately address SLT-related health disparities across multiple AI
      communities.

PMID- 28447179
TI  - Influence of Inherent Mechanophenotype on Competitive Cellular Adherence.
AB  - Understanding the role of mechanophenotype in competitive adherence of cells to
      other cells versus underlying substrates can inform such processes as tissue
      development, cancer progression, and wound healing. This study investigated how
      mechanophenotype, defined by whole-cell, elastic/viscoelastic properties for the
      perinuclear region, and cellular assembly are intertwined through the
      mechanosensing process. Atomic force microscopy was used to characterize the
      temporal elastic/viscoelastic properties of individual and assembled fibroblasts
      grown on substrates with elastic moduli above, below, or similar to whole-cell
      mechanophenotypes measured for three, genetically modified cell lines. All cells
      were at their most compliant immediately after plating but transitioned to
      distinct, stiffer mechanophenotypes by Day 1 after acclimation. This mechanical
      state, and cellular assembly/morphology, did not change significantly over the
      following three days of testing, regardless of substrate compliance or cellular
      organization (multi-cell nodules/plaques or single cells). Interestingly, cells
      formed 3D nodules when attached to substrates with elastic moduli less than their
      own but spread readily on substrates with moduli equal to or greater than their
      own, suggesting a preference to adhere to the stiffest surface sensed (substrate
      or cell). This suggests that inherent mechanophenotype plays a role as a
      competing surface during microenvironment mechanosensing and subsequent cell-cell
      substrate organization.

PMID- 28447181
TI  - SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC
      Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice
      with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a
      DPP4 Inhibitor.
AB  - PURPOSE: We assessed whether (1) dapagliflozin (Dapa, an SGLT2-inhibitor)
      attenuates the deterioration of heart function Nlrp3 and inflammasome activation
      in diabetic mice. (2) The effects can be augmented with saxagliptin (Saxa), a
      DDP4-inhibitor. (3) Dapa effect is possibly SGLT2-independent on
      cardiofibroblasts in vitro. METHODS: Type 2 diabetic (BTBR ob/ob) and wild-type
      (WT) mice received vehicle, Dapa, or Dapa+Saxa for 8 weeks. Glucose tolerance
      test and echocardiogram were performed. Cardiofibroblasts from WT and BTBR hearts
      were incubated with Dapa and exposed to LPS. RESULTS: Left ventricular ejection
      fraction (LVEF) was 81 +/- 1% in the WT and 53 +/- 1% in the T2D-cont mice. Dapa
      and Dapa+Saxa improved LVEF to 68 +/- 1 and 74.6 +/- 1% in the BTBR mice (p <
      0.001). The mRNA levels of NALP3, ASC, IL-1beta, IL-6, caspase-1, and TNFalpha
      were significantly higher in the BTBR compared to the WT hearts; and Dapa and
      Dapa+Saxa significantly attenuated these levels. Likewise, protein levels of
      NLRP3, TNFalpha, and caspase-1 were higher in the BTBR compared to the WT hearts
      and Dapa, and to a greater extent Dapa+Saxa, attenuated the increase in the BTBR
      mice. Collagen-1 and collagen-3 mRNA levels significantly increased in the BTBR
      mice and these increases were attenuated by Dapa and Dapa+Saxa. P-AMPK/total-AMPK
      ratio was significantly lower in the BTBR mice than in the WT mice. Dapa and
      Dapa+Saxa equally increased the ratio in the BTBR mice. This in vitro study
      showed that NALP3, ASC, IL-1beta, and caspase-1 mRNA levels were higher in the
      BTBR cardiofibroblasts and attenuated with Dapa. The effect was AMPK-dependent
      and SGLT1-independent. CONCLUSIONS: Dapa attenuated the activation of the
      inflammasome, fibrosis, and deterioration of LVEF in BTBR mice. The anti
      inflammatory, anti-fibrotic effects are likely SGLT2- and glucose-lowering
      independent, as they were replicated in the in vitro model. The effects on
      remodeling were augmented when Saxa was added to Dapa. Yet, adding Saxa to Dapa
      did not result in a greater effect on myocardial fibrosis and collagen levels.

PMID- 28447182
TI  - Co(II) Complexes of4-((3-ethoxy-2-hydroxybenzylidene)amino)-N-(thiazol-2
      yl)benzenesulphonamide and 4-((pyridin-2-ylmethylene)amino)-N-(thiazol-2
      tl)benzenesulfonamide: Synthesis, Fluorescence Properties and Anticancer
      Activity.
AB  - Two new Co(II) complexes of 4-((3-ethoxy-2-hydroxybenzylidene)amino)-N-(thiazol-2
      yl)benzenesulphonamide and 4-((pyridin-2-ylmethylene)amino)-N-(thiazol-2
      yl)benzene sulfonamide were synthesised. The structure of the complexes was
      identified by elemental analysis, FT-IR, electronic, EI mass, Powder XRD spectra
      and magnetic moment. The TG and DTA patterns of the complexes were supported the
      structures. The fluorescence quenching of these complexes with alizarin dye were
      premeditated and the free energy change (?Get) for electron transfer process was
      designed by Rehm-Weller equation. The [Co(L1-H)2(H2O)2] and [Co(L2)2(H2O)2].2H2O
      were submitted for in vitro cytotoxicity studies in human breast cancer cell line
      (MCF 7).

PMID- 28447183
TI  - Optical and Photophysical Investigation of (2E)-1-(2,5-Dimethylfuran-3-Yl)-3-(9
      Ethyl-9H-Carbazol-3-Yl)Prop-2-en-1-One (DEPO) by Spectrofluorometer in Organized
      Medium.
AB  - (2E)-1-(2,5-dimethylfuran-3-yl)-3-(9-ethyl-9H-carbazol-3-yl)prop-2-en-1-one
      (DEPO) was prepared by the reaction of 9-ethyl-9H-carbazole-3-carbaldehyde with 1
      (2,5-dimethylfuran-3-yl)ethanone under microwave irradiation. The structure of
      DEPO was established experimentally by EI-MS, FT-IR, 1H and 13C NMR spectral
      studies. Electronic absorption and emission spectra of DEPO were studied in
      different solvents on the basis of polarities, and the obtain data were used to
      determine the solvatochromic properties such as extinction coefficient,
      oscillator strength, transition dipole moment, stokes shift, fluorescence quantum
      yield and photochemical quantum yield. Photochemical quantum yield (Phi c ) of
      DEPO dye was determined in different solvent. The dye comparatively photostable
      in DMSO but undergoes photodecomposition in chloro methane solvents. The DEPO dye
      may be use as probe or quencher to determine critical micelle concentration (CMC)
      of cetyltri methyl ammonium bromide (CTAB) and sodium dodecyl sulfate (SDS).

PMID- 28447184
TI  - Electromyographic evaluation of high-intensity elastic resistance exercises for
      lower extremity muscles during bed rest.
AB  - PURPOSE: Prolonged hospital bed rest after severe injury or disease leads to
      rapid muscle atrophy and strength loss. Therefore, the main aim of this study was
      to evaluate the efficacy of lower extremity strengthening exercises using elastic
      resistance that can be performed while lying in a hospital bed. METHODS: Using a
      cross-sectional design, 22 healthy individuals performed three consecutive
      repetitions of 14 different lower extremity exercises using elastic resistance,
      with a perceived intensity corresponding to 8 on the Borg CR-10 scale. Surface
      electromyography was measured on 13 lower extremity muscles and normalized to the
      maximal EMG (nEMG). Likewise, exercise satisfaction was evaluated by a
      questionnaire. RESULTS: All participants were able to perform all exercises
      without discomfort and generally rated them satisfactory. High levels of muscle
      activity were observed for all prime movers. For example, the "femoris muscle
      setting" exercise showed high levels of muscle activity for rectus femoris,
      vastus lateralis, and vastus medialis (79, 75, and 79% nEMG, respectively), while
      biceps femoris and semitendinosus were highly active during the prone knee
      flexion exercise with (72 and 71% nEMG, respectively) and without Kinesiology
      Tape (73 and 77% nEMG, respectively). CONCLUSION: High levels of muscle activity
      in the lower extremities can be achieved using elastic resistance exercises
      performed when lying in a hospital bed. Even though performed on healthy
      individuals, the present study has the potential to provide a reference table of
      exercises to select from when individualizing and progressing strengthening
      exercises during the early rehabilitation of bedridden individuals.

PMID- 28447185
TI  - Maximum rate of sweat ions reabsorption during exercise with regional
      differences, sex, and exercise training.
AB  - PURPOSE: It is recently reported that determining sweat rate (SR) threshold for
      increasing galvanic skin conductance (GSC) would represent a maximum rate of
      sweat ion reabsorption in sweat glands. We evaluate the maximum rate of sweat ion
      reabsorption over skin regions, sex, and long-term exercise training by using the
      threshold analysis in the present study. METHODS: Ten males (2 untrained, 4
      sprinters, and 4 distance runners) and 12 females (5 untrained, 4 sprinters, and
      3 distance runners) conducted graded cycling exercise for 45 min at low, middle,
      and high exercise intensities (heart rate 100-110, 120-130, and 140-150
      beats/min, respectively) for 10, 15, and 20 min, respectively, at 30  degrees C
      and 50% relative humidity. Comparisons were made between males and females and
      among untrained individuals, distance runners, and sprinters on the back and
      forearm. RESULTS: SR threshold for increasing GSC on back was significantly
      higher than that of forearm (P < 0.05) without any sex differences (back 0.70 +/-
      0.08 and 0.61 +/- 0.04, forearm 0.40 +/- 0.05 and 0.45 +/- 0.06 mg/cm2/min for
      males and females, respectively). Distance runners and sprinters showed higher SR
      threshold for increasing GSC than that of untrained subjects on back (P < 0.05)
      but not on forearm (back 0.45 +/- 0.06, 0.83 +/- 0.06, and 0.70 +/- 0.04, forearm
      0.33 +/- 0.04, 0.49 +/- 0.02, and 0.39 +/- 0.07 mg/cm2/min for untrained
      subjects, distance runners, and sprinters, respectively). CONCLUSION: These
      results suggest that the maximum sweat ion reabsorption rate on the back is
      higher than that of forearm without sex differences. Furthermore, exercise
      training in distance runners and sprinters improves the maximum sweat ion
      reabsorption rate on the back.

PMID- 28447187
TI  - The enteric nervous system: another forgotten autonomic target in viral
      infections?

PMID- 28447186
TI  - Comparison of the recovery response from high-intensity and high-volume
      resistance exercise in trained men.
AB  - PURPOSE: The purpose of this study was to compare the physiological responses of
      a high-volume (HV; 8 sets of 10 repetitions) versus high-intensity (HI; 8 sets of
      3 repetitions) exercise protocol in resistance-trained men. METHODS: Twelve men
      (24.5 +/- 4.2 years; 82.3 +/- 8.4 kg; 175.2 +/- 5.5 cm) with 6.3 +/- 3.4 years of
      resistance training experience performed each protocol in a counterbalanced,
      randomized order. Performance [counter movement jump peak power (CMJP),
      isokinetic (ISOK) and isometric leg extension (MVIC), isometric mid-thigh pull
      (IMTP), and isometric squat (ISQ)] and muscle morphological [cross-sectional area
      (CSA) of vastus lateralis] assessments were performed at baseline (BL), 30-min (P
      30 min), 24-h (P-24 h), 48-h (P-48 h), and 72-h (P-72 h) post-exercise for each
      testing session. In addition, endocrine (testosterone and cortisol), inflammatory
      [interleukin-6 (IL-6) and C-reactive protein (CRP)], and markers of muscle damage
      [creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin (Mb)] were
      assessed at the same time points. RESULTS: Significantly greater reductions in
      CMJP (p < 0.001), and peak torque during both ISOK (p = 0.003) and MVIC (p =
      0.008) at P-30 min were detected in HV compared to HI protocol. MVIC was still
      impaired at P-72 h following the HV protocol, while no differences were noted
      following HI. Markers of muscle damage (LDH, CK, and Mb) were significantly
      elevated following both HV and HI (p < 0.05), while cortisol and IL-6
      concentrations were significantly elevated at P-30 min following HV only (p <
      0.001 and p < 0.05, respectively). CONCLUSIONS: Results indicate that high-volume
      resistance exercise results in greater performance deficits, and a greater extent
      of muscle damage, than a bout of high-intensity resistance exercise.

PMID- 28447188
TI  - Chemometric Evaluation of Elemental Imbalances in the Scalp Hair of Valvular
      Heart Disease Patients in Comparison with Healthy Donors.
AB  - The present study deals with the plausible association between the trace
      elemental imbalances and the emergence of valvular heart disease (VHD). A total
      of 14 elements including Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Pb, Sr and Zn
      in the scalp hair of VHD patients and healthy donors were analysed by flame
      atomic absorption spectrophometry employing wet acid digestion methodology.
      Median levels of Cu, Fe, Mg, Mn and Sr in the scalp hair of patients were
      significantly higher compared to those of the healthy donors, while the median
      concentrations of K and Na were found to be considerably higher in the scalp hair
      of the healthy donors. In addition, substantially elevated Cu/Zn value in
      patients indicated the prevalence of inflammatory processes inside the body. The
      correlation coefficients among the elements in the hair of VHD patients were
      significantly diverse compared to those of the healthy donors. Multivariate
      statistical methods showed noticeably dissimilar apportionment of the elements in
      the two groups. Variations in the elemental levels were also observed with
      gender, habitat, dietary/smoking habits and occupations of both donor groups.
      Overall, the study revealed significant imbalances among the essential and toxic
      elements in the scalp hair of VHD patients compared to those of the healthy
      subjects.

PMID- 28447189
TI  - Potentiometric Determination of Fluoride Concentration in Beers.
AB  - Beer is a widely consumed drink throughout the world, and because its manufacture
      involves the use of water, beer can be, in some cases, a source of fluorides. For
      this reason, the objective of this study was to determine the concentration of
      fluorides in 50 samples of beers from different sources sold in two different
      types of container (aluminum can and glass bottle). The possible significant
      differences between the different types of packaging and the intake of fluoride
      from the consumption of these beers were evaluated. The concentration of fluoride
      in beers has been determined using the potentiometric method of fluoride
      determination by standard addition. The concentration of fluoride ranged between
      0.06 and 1.77 mg/L. In general, the concentration was below 1 mg/L, except for
      three beer samples from Ireland and the USA, whose concentration was over 1.5
      mg/L. No significant differences were found between the types of packaging. The
      contribution of fluoride to the diet from beer consumption is not high (<27%);
      however, it is necessary to warn consumers whenever they are in areas of high
      concentrations of fluoride in the water supply.

PMID- 28447190
TI  - Regulation of NEAT1/miR-214-3p on the growth, migration and invasion of
      endometrial carcinoma cells.
AB  - OBJECTIVE: To investigate the function and mechanism of lnc NEAT1 in regulating
      the growth, migration and invasion of endometrial carcinoma (EC) cells. MATERIALS
      AND METHODS: NEAT1 and miR-214-3p levels were measured by qRT-PCR. The protein
      levels of HMGA1, beta-catenin, c-myc and MMP9 were evaluated by Western blot. The
      effects of NEAT1, HMGA1, miR-214-3p on the viability, migration and invasion of
      HEC-1A cells were accessed by WST-1 assay and transwell migration/invasion assay.
      The effect of miR-214-3p on Wnt signaling activity was tested by luciferase
      reporter assay. RESULTS: NEAT1, HMGA1 and beta-catenin were significantly
      upregulated in EC tissues, and miR-214-3p was significantly downregulated. NEAT1
      promoted the growth, migration and invasion of HEC-1A cells, and mRNA level of
      Wnt/beta-catenin downstream genes c-myc and MMP9. In addition, HMGA1 upregualted
      the protein and mRNA levels of Wnt/beta-catenin downstream genes c-myc and MMP9,
      and could improve cell viability, and increase numbers of migration and invasion
      of HEC-1A cells. miR-214-3p overexpression inhibited the proliferation, migration
      and invasion of HEC-1A cells, while NEAT1 overexpression reversed these effects.
      miR-214-3p overexpression inhibited the activity of Wnt/beta-catenin pathway,
      while NEAT1 overexpression reversed this effect. Then, si-HMGA1 reduced the
      activity of Wnt/beta-catenin pathway. Moreover, we found NEAT1 and HMGA1 bound to
      miR-214-3p by luciferase reporter assay, and NEAT1 and HMGA1 expression were
      negatively correlated with miR-214-3p. CONCLUSION: NEAT1 regulates HMGA1 via miR
      214-3p to regulate Wnt/beta-catenin pathway, thus promotes the growth, migration
      and invasion of HEC-1A cells.

PMID- 28447191
TI  - The human cytomegalovirus chemokine receptor homolog encoded by US27.
AB  - The genome of human cytomegalovirus contains four genes that encode chemokine
      receptor homologs. Of these, the protein encoded by US27 is of particular
      interest today because it is currently one of the viral G-protein coupled
      receptors that remain classified as an orphan receptor. This review explains what
      is presently understood about this glycoprotein: its biochemistry, its location
      in infected cells, and its apparent function. While there are still many
      questions that remain about these topics and more, we also discuss the utility of
      the US27-encoded glycoprotein as a new target for antiviral intervention.

PMID- 28447192
TI  - Rescue of a wild-type rabies virus from cloned cDNA and assessment of the
      proliferative capacity of recombinant viruses.
AB  - Reverse genetic systems (RGS) have been widely used for fixed rabies virus (RABV)
      strains. However, RGS, for wild-type (wt) strains, have been seldom reported
      despite the value of this approach in defining the biological characteristics of
      these strains. In this work, we developed a wt RGS using a swine-origin RABV
      strain (GD-SH-01) for the first time. In order to have a better understanding of
      the contribution and function of individual gene on viral proliferation for wt
      RABV isolates, we constructed a full-length cDNA clone of GD-SH-01 and exchanged
      the single genes encoding RABV protein of a highly attenuated RABV strain HEP
      Flury with those of the virulent strain. Analysis of the viral growth kinetics,
      cell-to-cell spread, and genomic RNA (gRNA) synthesis of the both the rescued and
      parental virus strains revealed that replacement of the HEP-Flury N or L genes
      with those from GD-SH-01 resulted in higher proliferative capacity of both
      chimeric rHEP-shN and rHEP-shL while the former seemed to have a better viral
      gRNA synthesis ability, the latter spread faster. Replacement of HEP-Flury P gene
      with GD-SH-01 P gene resulted in reduction of the virus titer in cell culture
      supernatants with a poor replicative and spreading ability. However, replacement
      of HEP-Flury M or G genes with those from GD-SH-01 seemed to impact less on viral
      proliferation. Taken together, we show that we have successfully rescued a wt
      RABV strain, and assessed the impact of each gene on viral proliferative capacity
      using a series of single-gene-substituted viruses.

PMID- 28447194
TI  - Residency Diary: My Second Year: November 2016-December 2016.

PMID- 28447193
TI  - Ebola and Marburg virus vaccines.
AB  - The filoviruses, Ebola virus (EBOV), and Marburg virus (MARV), are among the most
      pathogenic viruses known to man and the causative agents of viral hemorrhagic
      fever outbreaks in Africa with case fatality rates of up to 90%. Nearly 30,000
      infections were observed in the latest EBOV epidemic in West Africa; previous
      outbreaks were much smaller, typically only affecting less than a few hundred
      people. Compared to other diseases such as AIDS or Malaria with millions of cases
      annually, filovirus hemorrhagic fever (FHF) is one of the neglected infectious
      diseases. There are no licensed vaccines or therapeutics available to treat EBOV
      and MARV infections; therefore, these pathogens can only be handled in maximum
      containment laboratories and are classified as select agents. Under these
      limitations, a very few laboratories worldwide conducted basic research and
      countermeasure development for EBOV and MARV since their respective discoveries
      in 1967 (MARV) and 1976 (EBOV). In this review, we discuss several vaccine
      platforms against EBOV and MARV, which have been assessed for their protective
      efficacy in animal models of FHF. The focus is on the most promising approaches,
      which were accelerated in clinical development (phase I-III trials) during the
      EBOV epidemic in West Africa.

PMID- 28447195
TI  - Salivary miR-16, miR-191 and miR-223: intuitive indicators of dominant ovarian
      follicles in buffaloes.
AB  - Estrus or sexual receptivity determination is utmost important for efficient
      breeding programs for female buffaloes. Prominent estrus behavioral symptoms are
      the result of several molecular and neuroendocrine events involving the ovary and
      the brain. Expression of estrus behavior is poor in buffaloes during the summer
      season. Hence, the discovery of biomarkers specific to the estrus stage or its
      related ovarian events, like the presence of dominant ovarian follicle, is
      helpful for developing an easy estrus determination method. MicroRNA are small
      non-coding RNA with a potential to be biomarkers. Therefore, the present study
      targeted to investigate the potential of estrogen responsive miRNAs (miR-24, miR
      200c, miR-16, miR-191, miR-223 and miR-203) as estrus biomarkers in buffalo
      saliva, a non-invasive fluid representing animals' pathophysiology. There was a
      significant (P < 0.05) increase in the salivary presence of the miR-16, miR-191
      and miR-223 at 6th and 18th-19th days than the 0 day (estrus), 10th day and the
      following consecutive estrus day. These observations may indicate an association
      between the representative lower presence of these miRNA in saliva and the
      presence of dominant ovarian follicles. To test this association, pathway
      analysis, target gene identification, functional annotation and protein-protein
      interaction networks (PPI) were performed for miR-16, miR-191 and miR-223 by
      different bioinformatics tools. Interestingly, the top pathways (fatty acid
      biosynthesis and oocyte meiosis), target genes (FGF, BDNF and IGF1) and PPI hub
      genes (KRAS, BCL2 and IGF1) of these miRNAs were found essential for ovarian
      follicular dominance. In conclusion, the miR-16, miR-191 and miR-223 may not be
      the perfect estrus stage-specific biomarkers. However, their lower presence in
      saliva at estrus and 9th-10th day of estrous cycles, when the ovary usually has a
      dominant follicle in buffaloes, may intuitively indicate the follicular
      dominance. Further studies are needed to prove this association in a large
      population.

PMID- 28447196
TI  - The axon degeneration gene SARM1 is evolutionarily distinct from other TIR domain
      containing proteins.
AB  - Many forms of neurodegenerative disease are characterized by Wallerian
      degeneration, an active program of axonal destruction. Recently, the important
      player which enacts Wallerian degeneration was discovered, the multidomain
      protein SARM1. Since the SARM1 protein has classically been thought of as an
      innate immune molecule, its role in Wallerian degeneration has raised questions
      on the evolutionary forces acting on it. Here, we synthesize a picture of SARM1's
      evolution through various organisms by examining the molecular and genetic
      changes of SARM1 and the genes around it. Using proteins that possess domains
      homologous to SARM1, we established distances and Ka/Ks values through 5671
      pairwise species-species comparisons. We demonstrate that SARM1 diverged across
      species in a pattern similar to other SAM domain-containing proteins. This is
      surprising, because it was expected that SARM1 would behave more like its TIR
      domain relatives. Going along with this divorce from TIR, we also noted that
      SARM1's TIR is under stronger purifying selection than the rest of the TIR domain
      containing proteins (remaining highly conserved). In addition, SARM1's synteny
      analysis reveals that the surrounding gene cluster is highly conserved,
      functioning as a potential nexus of gene functionality across species. Taken
      together, SARM1 demonstrates a unique evolutionary pattern, separate from the TIR
      domain protein family.

PMID- 28447197
TI  - Role of Zinc in the Development/Progression of Alcoholic Liver Disease.
AB  - OPINION STATEMENT: Many variables, aside from the amount and duration of alcohol
      consumption, play a role in the development and progression of alcoholic liver
      disease (ALD). One critical factor that can be modified is diet/nutrition. We
      have made major recent advances in our understanding of the interactions of
      nutrition and ALD. In this article, we review advances made in zinc
      metabolism/therapy for ALD. There is major zinc dyshomeostasis with ALD which is
      mediated, in part, by poor intake and absorption, increased excretion, and
      altered zinc transporters, especially ZIP14. Zinc deficiency plays an etiologic
      role in multiple mechanisms of ALD, ranging from intestinal barrier dysfunction
      to hepatocyte apoptosis. Zinc supplementation is highly effective at correcting
      these ALD mechanisms and preventing/treating experimental ALD. There is no Food
      and Drug Administration (FDA) approved therapy for any stage of ALD. Because
      animal and human data suggest that zinc deficiency occurs early in the course of
      ALD, we treat most ALD patients with daily oral zinc supplementation (220 mg zinc
      sulfate which contains 50 mg elemental zinc).

PMID- 28447198
TI  - A Twist in the Tale.

PMID- 28447199
TI  - A Novel Reconstruction Technique During Pancreaticoduodenectomy After Roux-En-Y
      Gastric Bypass: How I do It.
AB  - The altered anatomy in patients after bariatric surgery who have undergone a Roux
      en-Y gastric bypass may pose a technical challenge for surgical removal of the
      pancreatic head. We treat patients with pancreas cancer with multimodality
      therapy in a neoadjuvant fashion followed by pancreaticoduodenectomy (PD). In
      patients with Roux-en-Y gastric bypass anatomy, the gastric remnant is preserved
      and used for pancreaticogastrostomy reconstruction and subsequently drained by
      the same jejunal limb used for the hepaticojejunostomy. This method of
      reconstruction takes advantage of the previous surgically altered anatomy and
      avoids the morbidity of a gastric remnant resection at the time of PD.

PMID- 28447200
TI  - Skyline retention and retroactive interference in the navigating Australian
      desert ant, Melophorus bagoti.
AB  - Visual cues commonly aid solitary foraging ants. Specifically, foragers can use
      the skyline where terrestrial landmarks meet the sky. Foraging ants show a
      remarkable affinity to retain these terrestrial cues, developing lifelong
      memories of the nest site panorama. Here we explore foragers' ability to retain
      skyline cues of resource locations at some distance from the nest through
      experiments with artificial skylines erected around a resource location. We also
      tested the foragers' memories of one skyline at several time points after the
      skyline was replaced by a different one. During retention testing, foragers
      appear able to retain robust memories of these skylines over periods (5 days)
      that surpass their average life span. Exposure to the nest panorama during these
      periods did not interfere with navigational performance at the distant skyline.
      Foragers in the replacement experiment initially oriented correctly to both
      skylines. Thereafter, the foragers' headings in tests with the first skyline
      gradually shifted away from the correct homeward direction. We argue that new
      skyline memories cause retroactive interference in the retention of previously
      learned skylines. Skyline memories may compete during memory retrieval, or may be
      retrieved in association with context cues present in the current testing
      paradigm such as vector length.

PMID- 28447201
TI  - Teleophthalmology image-based navigated retinal laser therapy for diabetic
      macular edema: a concept of retinal telephotocoagulation.
AB  - BACKGROUND: To determine the feasibility and efficacy of a retinal
      telephotocoagulation treatment plan for diabetic macular edema. METHODS:
      Prospective, interventional cohort study at two clinical sites. Sixteen eyes of
      ten subjects with diabetic macular edema underwent navigated focal laser
      photocoagulation using a novel teleretinal treatment plan. Clinic 1 (King Khaled
      Eye Specialist Hospital, Riyadh, Saudi Arabia) collected retinal images and
      fundus fluorescein angiogram. Clinic 2 (Palmetto Retina Center, West Columbia,
      SC, USA) created image-based treatment plans based on which macular laser
      photocoagulation was performed back at clinic 1. The primary outcome of the study
      was feasibility of image transfer and performing navigated laser photocoagulation
      for subjects with diabetic macular edema between two distant clinics. Secondary
      measures were change in best-corrected visual acuity (BCVA) and central retinal
      thickness (CRT) by spectral-domain optical coherence tomography at 3 months after
      treatment. RESULTS: The teleretinal treatment plan was able to be successfully
      completed in all 16 eyes. The mean logMAR BCVA at baseline was 0.49 +/- 0.1,
      which remained stable (0.45 +/- 0.1) 3 months after treatment (p = 0.060). The
      CRT improved from 290.1 +/- 37.6 MUm at baseline to 270.8 +/- 27.7 MUm 3 months
      after treatment (p = 0.005). All eyes demonstrated improvement in the area of
      retinal edema after laser photocoagulation, and no eyes demonstrated visual
      acuity loss 3 months after treatment. CONCLUSION: This study introduces the
      concept of retinal telephotocoagulation for diabetic macular edema, and
      demonstrates the feasibility and safety of using telemedicine to perform
      navigated retinal laser treatments regardless of geographical distance.

PMID- 28447202
TI  - Exploring the relationship between perceived barriers to healthy eating and
      dietary behaviours in European adults.
AB  - PURPOSE: Dietary behaviours may be influenced by perceptions of barriers to
      healthy eating. Using data from a large cross-European study (N = 5900), we
      explored associations between various perceived barriers to healthy eating and
      dietary behaviours among adults from urban regions in five European countries and
      examined whether associations differed across regions and socio-demographic
      backgrounds. METHODS: Frequency of consumption of fruit, vegetables, fish, fast
      food, sugar-sweetened beverages, sweets, breakfast and home-cooked meals were
      split by the median into higher and lower consumption. We tested associations
      between barriers (irregular working hours; giving up preferred foods; busy
      lifestyle; lack of willpower; price of healthy food; taste preferences of family
      and friends; lack of healthy options and unappealing foods) and dietary variables
      using multilevel logistic regression models. We explored whether associations
      differed by age, sex, education, urban region, weight status, household
      composition or employment. RESULTS: Respondents who perceived any barrier were
      less likely to report higher consumption of healthier foods and more likely to
      report higher consumption of fast food. 'Lack of willpower', 'time constraints'
      and 'taste preferences' were most consistently associated with consumption. For
      example, those perceiving lack of willpower ate less fruit [odds ratio (OR) 0.57;
      95% confidence interval (CI) 0.50-0.64], and those with a busy lifestyle ate less
      vegetables (OR 0.54; 95% CI 0.47-0.62). Many associations differed in size, but
      not in direction, by region, sex, age and household composition. CONCLUSION:
      Perceived 'lack of willpower', 'time constraints' and 'taste preferences' were
      barriers most strongly related to dietary behaviours, but the association between
      various barriers and lower intake of fruit and vegetables was somewhat more
      pronounced among younger participants and women.

PMID- 28447203
TI  - The effectiveness of daily supplementation with 400 or 800 ug/day folate in
      reaching protective red blood folate concentrations in non-pregnant women: a
      randomized trial.
AB  - PURPOSE: Folate required to achieve desirable red blood cell (RBC) folate
      concentrations within 4-8 weeks pre-pregnancy is not known. We studied the effect
      of supplementation with 400 or 800 ug/day folate in achieving RBC-folate >=906
      nmol/L. METHODS: Non-pregnant women were randomized to receive multinutrient
      supplements containing 400 ug/day (n = 100) or 800 ug/day (n = 101) folate [folic
      acid and (6S)-5-CH3-H4folate-Ca (1:1)]. The changes of folate biomarkers were
      studied after 4 and 8 weeks in the 198 women who returned at least for visit 2.
      RESULTS: At baseline, 12 of the 198 participants (6.1%) had RBC-folate <340
      nmol/L, but 88% had levels <906 nmol/L. The RBC-folate concentrations increased
      significantly in the 800 ug/day (mean +/- SD = 652 +/- 295 at baseline; 928 +/-
      330 at 4 weeks; and 1218 +/- 435 nmol/L at 8 weeks) compared with the 400 ug/day
      [632 +/- 285 at baseline (p = 0.578); 805 +/- 363 at 4 weeks (p < 0.001); 1021 +/
      414 nmol/L at 8 weeks (p < 0.001)]. The changes of RBC-folate were greater in
      the 800 ug/day than in the 400 ug/day at any time (changes after 8 weeks: 566 +/-
      260 vs. 389 +/- 229 nmol/L; p < 0.001). Significantly more women in the 800 ug
      group achieved desirable RBC-folate concentrations at 4 weeks (45.5 vs. 31.3%; p
      = 0.041) or 8 weeks (83.8 vs. 54.5%; p < 0.001) compared with the 400 ug group.
      RBC-folate levels below the population median (590 nmol/L) were associated with a
      reduced response to supplements. CONCLUSIONS: 88% of the women had insufficient
      RBC-folate to prevent birth defects, while 6.1% had deficiency. Women with low
      RBC-folate were unlikely to achieve desirable levels within 4-8 weeks, unless
      they receive 800 ug/day. The current supplementation recommendations are not
      sufficient in countries not applying fortification. TRIALS REGISTER: The trial
      was registered at The German Clinical Trials Register: DRKS-ID: DRKS00009770.

PMID- 28447204
TI  - Comparative transcriptome profiling of freezing stress responses in loquat
      (Eriobotrya japonica) fruitlets.
AB  - Loquat (Eriobotrya japonica Lindl.) is an important subtropical, commercial fruit
      in China. It blossoms during autumn and winter in most areas of China and its
      fruitlets usually suffer from freezing stress. However, studies about the
      mechanisms underlying freezing stress in loquat are very limited. The gene
      expression profiles of loquat fruitlets subjected to freezing (G2 library) versus
      non-treated ones (G1 library) were investigated using Illumina sequencing
      technology to elucidate the molecular mechanisms and identify the genes that play
      vital roles in the freezing stress response. The results showed that
      approximately 157.63 million reads in total were obtained from freeze-treated and
      non-treated loquat fruitlets. These reads were assembled into 87,379 unigenes
      with an average length of 710 bp and an N50 of 1,200 bp. After comparing the
      profiles obtained from the G1 and G2 libraries, 2,892 differentially expressed
      genes were identified, of which 1,883 were up-regulated and 1,009 were down
      regulated in the treated samples compared to non-treated ones. These unigenes
      showed significant differences in expression for carbohydrate transport and
      metabolism, amino acid metabolism, energy metabolism, and lipid metabolism, which
      are involved in defense against freezing stress. Glycolysis/gluconeogenesis was
      one of the most significantly regulated pathways. Freezing also significantly
      damaged the membrane system of loquat fruitlets, and several defense mechanisms
      were induced. Some selected genes related to low temperature resistance were
      validated by quantitative real-time PCR (qRT-PCR). The results revealed many
      genes and pathways that are part of freezing resistance processes and expand our
      understanding of the complex molecular events involved in freezing stress.

PMID- 28447205
TI  - Treatment with Geranylgeranylacetone Induces Heat Shock Protein 70 and Attenuates
      Neonatal Hyperoxic Lung Injury in a Model of Bronchopulmonary Dysplasia.
AB  - PURPOSE: Bronchopulmonary dysplasia (BPD) is a respiratory complication
      characterized by abnormal alveolar development in premature infants.
      Geranylgeranylacetone (GGA) can induce heat shock protein (HSP) 70, which has
      cytoprotective effects against various stressors. Here, we investigated whether
      GGA protected neonatal lungs from hyperoxic stress in a murine BPD model, and
      measured the serum HSP70 levels in preterm humans treated with oxygen. METHODS:
      Newborn mice were exposed to >90% oxygen and administered GGA or vehicle alone
      orally on days 1, 2, and 3 of life. At 2 days of age, HSP70 expression in the
      lung was determined by western blotting. At 8 days of age, the lungs were
      processed for histological analysis. Radial alveolar count (RAC) and mean linear
      intercept (MLI) were measured as parameters of alveolarization. Apoptosis was
      evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) method and cleaved caspase-3 immunohistochemistry. Serum HSP70
      levels in preterm humans treated with oxygen were measured by enzyme-linked
      immunosorbent assay. RESULTS: GGA administration enhanced the HSP70 expression to
      two-fold compared with normoxia-exposed and vehicle-treated mice. Hyperoxia
      reduced HSP70 expression, whereas GGA abrogated the effects. Hyperoxia-exposed
      mice exhibited more apoptotic cells in lung parenchyma and a more simplified
      alveolar structure with less RAC and larger MLI than normoxia-exposed mice. GGA
      suppressed the increase in apoptotic cells and the structural changes of the
      lungs induced by hyperoxia. Serum HSP70 levels of preterm human infants gradually
      decreased with age. CONCLUSIONS: GGA may attenuate hyperoxic injury in neonatal
      lungs and thereby may prevent the development of BPD.

PMID- 28447206
TI  - New urate depositions on dual-energy computed tomography in gouty arthritis
      during urate-lowering therapy.
AB  - Reduction of urate depositions in the joints, on dual-energy computed tomography
      (DECT), in patients with gout during urate-lowering therapy (ULT) was
      demonstrated in previous studies. The aim of this study was to further
      investigate the changes in distribution of urate deposits during ULT. This
      randomized controlled trial enrolled 46 patients diagnosed with gout from
      Zhongshan Hospital, China, between October 2013 and June 2014. Epidemiological
      data, serum uric acid level, and arthritis attacks were recorded at monthly
      follow-up visits. DECT of bilateral feet and ankles was performed at baseline and
      after 6 months of ULT. Overall, 163 areas of urate deposition were found in the
      46 patients; of these, 133/163 (81.6%) areas were associated with former
      arthritis attacks. On DECT at 6 months, the number of urate deposits decreased to
      126, with 68 areas disappearing and 31 new deposits areas. The mean volume of
      urate deposits at baseline was 1.3 +/- 3.8 cm3, decreasing to 0.6 +/- 2.1 cm3 at
      the end of 6 months (P = 0.01), with 3/46 (6.5%) patients showing complete
      disappearance of urate deposits. New urate depositions were found in 21/46
      (45.7%) patients, while urate depositions in some joints disappeared in some
      joints in 31/46 (67.4%) patients. High-sensitivity C-reactive protein was
      significantly lower in patients with new deposits (4.6 +/- 9.3 vs. 7.1 +/- 7.6
      mg/dL; P = 0.01). There is dynamic redistribution of urate depositions in gout
      patients receiving ULT.

PMID- 28447207
TI  - Prevalence of fibromyalgia in general population and patients, a systematic
      review and meta-analysis.
AB  - This study aims to estimate the reliable prevalence of fibromyalgia using meta
      analysis method. Available databanks were searched using appropriate keywords.
      According to the heterogeneity between the results (indicated by Cochrane and I
      square indices), random- or fixed-effects model was applied to combine the point
      prevalences. Meta-regression models were used to assess the suspected factors in
      the heterogeneity. In 65 selected papers, 81 evidences regarding prevalence of
      fibromyalgia among 3,609,810 subjects from general population and specific groups
      were investigated. The total prevalences (95% confidence intervals) of
      fibromyalgia among general population, women, men, patients referring to
      rheumatology and internal departments, patients with Irritable bowel syndrome
      (IBS), hemodialysis patients and those with type 2 diabetes mellitus were
      estimated as of 1.78% (1.65, 1.92), 3.98% (2.80, 5.20), 0.01% (-0.04, 0.06),
      15.2% (13.6, 16.90), 12.9% (12.70, 13.10), 6.30% (4.60, 7.90) and 14.80% (11.10,
      18.40), respectively. In addition, prevalence of fibromyalgia in specified groups
      varied from 3.90% in hemodialysis patients to 80% in patients suffering from
      Behcet syndrome. This meta-analysis showed that prevalence of fibromyalgia in
      general population was significantly lower than that in populations with some
      diseases.

PMID- 28447208
TI  - Squamous cell carcinoma of the lung associated with anti-Jo1 antisynthetase
      syndrome: a case report and review of the literature.
AB  - Antisynthetase syndrome is a heterogeneous idiopathic inflammatory myopathy. Anti
      Jo1 is the most common antibody found in this condition. Dermatomyositis is known
      to be associated with malignancy, but the association between antisynthetase
      syndrome and malignancy is not clearly established. We report a case of an
      association of squamous cell carcinoma of the lung and anti-Jo1 antisynthetase
      syndrome. A 67-year-old man presented with polyarthritis, muscle weakness of the
      pelvic girdle, "mechanic's hands," and weight loss. A diagnosis of antisynthetase
      syndrome was considered based on the clinical features and the presence of anti
      Jo1 antibodies. Positron emission tomography was performed because of weight loss
      and revealed a pulmonary hypermetabolic lesion. Histological findings revealed
      squamous cell carcinoma. The patient underwent lobectomy and is currently free of
      symptoms with regular monitoring. This unusual presentation of squamous cell
      carcinoma of the lung illustrates the need of a systematic approach to the
      diagnosis of antisynthetase syndrome. Positron emission tomography can be a
      useful imaging modality in the diagnosis of paraneoplastic syndromes associated
      with antisynthetase syndrome especially in the presence of warning
      signs/symptoms.

PMID- 28447209
TI  - Adjuvant concurrent chemoradiotherapy with low-dose daily cisplatin for
      extrahepatic bile duct cancer.
AB  - PURPOSE: We aimed to present the clinical outcomes of adjuvant concurrent
      chemoradiotherapy (CCRT) with low-dose daily cisplatin regimen compared to the
      conventional 5-fluorouracil (5-FU)-based regimen for extrahepatic bile duct
      cancer (EHBDC). METHODS: From October 1994 to April 2013, 41 patients received
      adjuvant CCRT with low-dose daily regimen or 5-FU-based regimens. Nineteen
      patients received low-dose of cisplatin just before every delivery of radiation
      therapy, and 21 patients received two cycles of 5-FU-based regimen during
      radiotherapy. We compared the clinical outcomes between two adjuvant CCRT
      regimens. RESULTS: Adjuvant CCRT with low-dose daily cisplatin showed comparable
      toxicity profiles compared with that of a 5-FU-based regimen. The median follow
      up time was 33 months (range, 5-205), and the 5-year overall survival (OS),
      locoregional recurrence-free survival (LRRFS), and distant metastasis-free
      survival (DMFS) were 34.2, 50.8, and 49.7%, respectively. Univariable analyses
      showed no significant differences in OS, LRRFS, and DMFS between the groups with
      two regimens. In multivariable analyses, chemotherapeutic regimen was a
      significant prognostic factor for OS, favoring the low-dose daily cisplatin
      regimen (HR = 2.491, p = 0.036) over 5-FU-based regimen, though not for LRRFS (p
      = 0.642) and DMFS (p = 0.756). CONCLUSIONS: Adjuvant CCRT with low-dose daily
      cisplatin regimen showed acceptable toxicities and survivals compared to those of
      the 5-FU-based regimen. Low-dose daily cisplatin can be one of the feasible
      regimens for adjuvant CCRT for EHBDC.

PMID- 28447210
TI  - MITF suppression by CH5552074 inhibits cell growth in melanoma cells.
AB  - PURPOSE: Although treatment of melanoma with BRAF inhibitors and immune
      checkpoint inhibitors achieves a high response rate, a subset of melanoma
      patients with intrinsic and acquired resistance are insensitive to these
      therapeutics, so to improve melanoma therapy other target molecules need to be
      found. Here, we screened our chemical library to identify an anti-melanoma agent
      and examined its action mechanisms to show cell growth inhibition activity.
      METHODS: We screened a chemical library against multiple skin cancer cell lines
      and conducted ingenuity pathway analysis (IPA) to investigate the mechanisms of
      CH5552074 activity. Suppression of microphthalmia-associated transcription factor
      (MITF) expression levels was determined in melanoma cells treated with CH5552074.
      Cell growth inhibition activity of CH5552074 was evaluated in MITF-dependent
      melanoma cell lines. RESULTS: We identified an anti-melanoma compound, CH5552074,
      which showed remarkable cell growth inhibition activity in melanoma cell lines.
      The IPA results suggested that CH5552074-sensitive cell lines had activated MITF.
      In further in vitro studies in the melanoma cell lines, a knockdown of MITF with
      siRNA resulted in cell growth inhibition, which showed that CH5552074 inhibited
      cell growth by reducing the expression level of MITF protein. CONCLUSIONS: These
      results suggest that CH5552074 can inhibit cell growth in melanoma cells by
      reducing the protein level of MITF. MITF inhibition by CH5552074 would be an
      attractive option for melanoma treatment.

PMID- 28447211
TI  - Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1
      single nucleotide polymorphism and older age in Japanese.
AB  - PURPOSE: Whether age and inter-individual variability of pharmacogenetics are
      risk factors for paclitaxel-induced peripheral neuropathy (PIPN) is inconclusive.
      This study was conducted to evaluate the influence of previously investigated
      single nucleotide polymorphisms (SNPs) and age, using genotype data from a
      prospective study of paclitaxel-related toxicity in Japanese patients with breast
      cancer. METHODS: Peripheral blood mononuclear cells from 127 Japanese women with
      breast cancer who received weekly adjuvant paclitaxel were used to genotypes
      SLCO1B3 T334G (rs4149117), CYP2C8 A1196G (rs10509681), ABCB1 C1236T (rs1128503),
      ABCB1 G2677T/A (rs2032582), and ABCB1 C3435T (rs1045642). Genotypic and clinical
      factors were investigated for associations with PIPN. RESULTS: Of the five SNPs
      evaluated, no SNPs were significantly associated with grade 2 or higher PIPN.
      However, ABCB1 1236 TT showed a trend to associate with grade 2 or higher PIPN
      compared to ABCB1 CT/CC (odds ratio 2.1, 95% CI 0.991-4.548, p = 0.051). In
      subgroup analysis, patients >=60 years old with an ABCB1 1236 TT had a higher
      incidence of >=grade 2 PIPN compared to patients with CT or CC genotype (p =
      0.027). On multivariable analysis, age >=60 years and the ABCB1 1236 TT showed a
      significant association with >=grade 2 PIPN (p = 0.005 and p = 0.034,
      respectively). CONCLUSIONS: ABCB1 1236 TT genotype and older age might be a
      predictor of PIPN, which diminishes quality of life of cancer survivors.

PMID- 28447212
TI  - Core curriculum case illustration: olecranon fracture.
AB  - This is the 31st installment of a series that will highlight one case per
      publication issue from the bank of cases available online as part of the American
      Society of Emergency Radiology (ASER) educational resources. Our goal is to
      generate more interest in and use of our online materials. To view more cases
      online please visit the ASER Core Curriculum and Recommendations for Study online
      at: http://www.erad.org/page/CCIP_TOC .

PMID- 28447213
TI  - Discordance Between Physician- and Patient-Reported Disease Severity in Adults
      with Atopic Dermatitis: A US Cross-Sectional Survey.
AB  - BACKGROUND: There is limited understanding of severity rating of atopic
      dermatitis in clinical practice. OBJECTIVES: To evaluate the agreement between
      physician- and patient-rated severity of atopic dermatitis. METHODS: Data were
      collected from the 2014 Adelphi US Atopic Dermatitis Disease Specific Programme,
      a cross-sectional survey of physicians and their patients with a history of
      moderate-to-severe atopic dermatitis; patients voluntarily completed a
      questionnaire. Current disease severity (mild/moderate/severe), based on personal
      judgment, was rated independently by patients and their physicians. The weighted
      kappa statistic identified level of agreement between physicians and patients.
      Bivariate analyses characterized agreement; multi-nomial logistic regression
      identified factors associated with discordance. RESULTS: Overall, 678 patients
      were included (369 [54.4%] were women, 525 [77.4%] were White, mean age was 39.3
      years). Agreement was moderate (weighted kappa = 0.52): compared with physician
      ratings, patient-rated severity was higher in 76 patients (11.2%), lower in 137
      patients (20.2%), and matched in 465 patients (68.6%). There were no differences
      in the rates of agreement between physician and patient ratings based on
      physician specialty (p = 0.6781), objective severity measures [Eczema Area and
      Severity Index score (p = 0.5308), percent body surface area affected (p =
      0.9872), and current systemic immunosuppressant use (p = 0.9197)]. Multivariate
      analysis showed patients with a worse quality of life (Dermatology Life Quality
      Index) were more likely to rate a higher severity (relative risk ratio 1.04, 95%
      confidence interval 1.00-1.08; p = 0.0460). Physicians were more likely to rate a
      higher severity with a greater physician-reported sleep disturbance (relative
      risk ratio 1.71, 95% confidence interval 1.01-2.89; p = 0.0440). CONCLUSIONS:
      Almost one-third of patients rated atopic dermatitis severity differently from
      their physicians, supporting the importance of the patient perspective in the
      severity assessment of atopic dermatitis and the need for greater communication
      between patients and physicians.

PMID- 28447214
TI  - EEG abnormalities and long term seizure outcome in high functioning autism.
AB  - Electroencephalographic abnormalities may occur in autistic spectrum disorders
      (ASD) even in the absence of clinical seizures. These abnormalities may vary from
      nonspecific changes to epileptiform abnormalities and are more common compared to
      the overall population. The level of intelligence is a significant risk factor
      for epilepsy in ASD. However, the relation between the functionality of the
      individuals with autism and the electroencephalographic (EEG) abnormalities, and
      the clinical significance of these abnormalities still remain relatively unclear.
      In this study we investigated the presence of EEG abnormalities in sixteen
      children diagnosed with high-functioning ASD. EEG recording was performed for at
      least 2 h and included at least 90 min of sleep activity. While none of the
      patients had clinical seizures, 5 patients (31.3%) were detected to have EEG
      abnormalities. Four of these were epileptiform (25%), and one patient developed
      seizure during follow-up. Our results support the fact that EEG abnormalities are
      observed at a higher rate also in ASD with a better functionality. The potential
      impact of EEG abnormalities on cognition and behavior, and the risk of epilepsy
      should be considered during long-term follow-up of these patients.

PMID- 28447216
TI  - Highly divergent cyclo-like virus in a great roundleaf bat (Hipposideros armiger)
      in Vietnam.
AB  - Members of the viral family Circoviridae are increasingly recognized worldwide.
      Bats seem to be natural reservoirs or dietary-related dispensers of these
      viruses. Here, we report a distantly related member of the genus Cyclovirus
      detected in the faeces of a great roundleaf bat (Hipposideros armiger).
      Interestingly, the novel virus lacks a Circoviridae-specific stem-loop structure,
      although a Geminiviridae-like nonamer sequence was detected in the large
      intergenic region. Based on these differences and its phylogenetic position, we
      propose that our new virus represents a distant and highly divergent member of
      the genus Cyclovirus. However it is lacking several characteristics of members of
      the genus, which raises a challenge in its taxonomic classification.

PMID- 28447215
TI  - Interplay between recombinant Hsp70 and proteasomes: proteasome activity
      modulation and ubiquitin-independent cleavage of Hsp70.
AB  - The heat shock protein 70 (Hsp70, human HSPA1A) plays indispensable roles in
      cellular stress responses and protein quality control (PQC). In the framework of
      PQC, it cooperates with the ubiquitin-proteasome system (UPS) to clear damaged
      and dysfunctional proteins in the cell. Moreover, Hsp70 itself is rapidly
      degraded following the recovery from stress. It was demonstrated that its fast
      turnover is mediated via ubiquitination and subsequent degradation by the 26S
      proteasome. At the same time, the effect of Hsp70 on the functional state of
      proteasomes has been insufficiently investigated. Here, we characterized the
      direct effect of recombinant Hsp70 on the activity of 20S and 26S proteasomes and
      studied Hsp70 degradation by the 20S proteasome in vitro. We have shown that the
      activity of purified 20S proteasomes is decreased following incubation with
      recombinant human Hsp70. On the other hand, high concentrations of Hsp70
      activated 26S proteasomes. Finally, we obtained evidence that in addition to
      previously reported ubiquitin-dependent degradation, Hsp70 could be cleaved
      independent of ubiquitination by the 20S proteasome. The results obtained reveal
      novel aspects of the interplay between Hsp70 and proteasomes.

PMID- 28447217
TI  - Swallowing Disorders in Schizophrenia.
AB  - Disorders of swallowing are poorly characterized but quite common in
      schizophrenia. They are a source of considerable morbidity and mortality in this
      population, generally as a result of either acute asphyxia from airway
      obstruction or more insidious aspiration and pneumonia. The death rate from acute
      asphyxia may be as high as one hundred times that of the general population. Most
      swallowing disorders in schizophrenia seem to fall into one of two categories,
      changes in eating and swallowing due to the illness itself and changes related to
      psychotropic medications. Behavioral changes related to the illness are poorly
      understood and often involve eating too quickly or taking inappropriately large
      boluses of food. Iatrogenic problems are mostly related to drug-induced
      extrapyramidal side effects, including drug-induced parkinsonism, dystonia, and
      tardive dyskinesia, but may also include xerostomia, sialorrhea, and changes
      related to sedation. This paper will provide an overview of common swallowing
      problems encountered in patients with schizophrenia, their pathophysiology, and
      management. While there is a scarcity of quality evidence in the literature, a
      thorough history and examination will generally elucidate the predominant problem
      or problems, often leading to effective management strategies.

PMID- 28447218
TI  - Pertuzumab/Trastuzumab/CT Versus Trastuzumab/CT Therapy for HER2+ Breast Cancer:
      Results from the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST).
AB  - BACKGROUND: Pertuzumab became a standard part of neoadjuvant therapy for human
      epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately
      halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment,
      providing a unique opportunity to determine biologically which clinical HER2+
      patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST
      classifies patients by both conventional and molecular subtyping. METHODS: Of 308
      clinical HER2+ patients enrolled in NBRST between 2011 and 2014 from 62 U.S.
      institutions, 297 received neoadjuvant chemotherapy (NCT) with HER2-targeted
      therapy and underwent surgery. This study compared the pathologic complete
      response (pCR) rate of BluePrint versus clinical subtypes with treatment,
      specifically differences between trastuzumab (T) treatment and trastuzumab and
      pertuzumab (T/P) treatment. RESULTS: In this study, 60% of the patients received
      NCT-T, and 40% received NCT-T/P. The overall pCR rate (ypT0/isN0) was 47%.
      BluePrint classified 161 tumors (54%) as HER2 type, with a pCR rate of 65%. This
      was significantly higher than the pCR rate for the 91 HER2+ tumors (31%)
      classified as luminal (18%) (p = 0.00001) and the 45 tumors (15%) classified as
      basal (44%) (p = 0.0166). The patients treated with T/P had higher pCR rates than
      those treated with trastuzumab alone. The difference was most pronounced in the
      BluePrint luminal patients (8 vs. 31%). The highest pCR was reached by the
      BluePrint HER2-type patients treated with T/P (76%). CONCLUSIONS: The addition of
      pertuzumab leads to increased pCR rates for all HER2+ patient groups except for
      the BluePrint basal-type patients. This better response was most pronounced for
      the BluePrint luminal-type patients.

PMID- 28447219
TI  - An EThcD-Based Method for Discrimination of Leucine and Isoleucine Residues in
      Tryptic Peptides.
AB  - An EThcD-based approach for the reliable discrimination of isomeric leucine and
      isoleucine residues in peptide de novo sequencing procedure has been proposed. A
      multistage fragmentation of peptide ions was performed with Orbitrap Elite mass
      spectrometer in electrospray ionization mode. At the first stage, z-ions were
      produced by ETD or ETcaD fragmentation of doubly or triply charged peptide
      precursor ions. These primary ions were further fragmented by HCD with broad-band
      ion isolation, and the resulting w-ions showed different mass for leucine and
      isoleucine residues. The procedure did not require manual isolation of specific z
      ions prior to HCD stage. Forty-three tryptic peptides (3 to 27 residues) obtained
      by trypsinolysis of human serum albumin (HSA) and gp188 protein were analyzed. To
      demonstrate a proper solution for radical site migration problem, three non
      tryptic peptides were also analyzed. A total of 93 leucine and isoleucine
      residues were considered and 83 of them were correctly identified. The developed
      approach can be a reasonable substitution for additional Edman degradation
      procedure, which is still used in peptide sequencing for leucine and isoleucine
      discrimination. Graphical Abstract ?.

PMID- 28447220
TI  - Track-weighted dynamic functional connectivity (TW-dFC): a new method to study
      time-resolved functional connectivity.
AB  - Interest in the study of brain connectivity is growing, particularly in
      understanding the dynamics of the structural/functional connectivity relation.
      Structural and functional connectivity are most often analysed independently of
      each other. Track-weighted functional connectivity (TW-FC) was recently proposed
      as a means to combine structural/functional connectivity information into a
      single image. We extend here TW-FC in two important ways: first, all the
      functional data are used without having to define a prior functional network (cf.
      TW-FC generates a map for a pre-specified network); second, we incorporate time
      resolved connectivity information, thus allowing dynamic characterisation of
      functional connectivity. We refer to this technique as track-weighted dynamic
      functional connectivity (TW-dFC), which fuses structural/functional connectivity
      data into a four-dimensional image, providing a new approach to investigate
      dynamic connectivity. The structural connectivity information effectively
      'constrains' the extremely large number of possible connections in the functional
      connectivity data (i.e. each voxel's connection to every other voxel), thus
      providing a way of reducing the problem's dimensionality while still maintaining
      key data features. The methodology is demonstrated in data from eight healthy
      subjects, and independent component analysis was subsequently applied to
      parcellate the corpus callosum, as an illustration of a possible application. TW
      dFC maps demonstrate that different white matter pathways can have very different
      temporal characteristics, corresponding to correlated fluctuations in the grey
      matter regions they link. A realistic parcellation of the corpus callosum was
      generated, which was qualitatively similar to topography previously reported. TW
      dFC, therefore, provides a complementary new tool to investigate the dynamic
      nature of brain connectivity.

PMID- 28447223
TI  - Prediction of rehabilitation needs after treatment of cervical cancer: a
      methodological mistake.

PMID- 28447222
TI  - Feeding strategies in pediatric cancer patients with gastrointestinal mucositis:
      a multicenter prospective observational study and international survey.
AB  - INTRODUCTION: Currently, there is no adequate prevention or treatment for both
      oral and gastrointestinal mucositis induced by chemotherapy and/or radiotherapy.
      Supportive care of symptoms plays a primary role during mucositis in the
      pediatric clinical setting. We aimed to get insight in the currently used feeding
      strategies in clinical practice in pediatric cancer patients with chemotherapy
      induced mucositis. METHODS: A prospective observational study was performed to
      identify feeding strategies after chemotherapy courses causing mucositis in
      almost all patients at the University Medical Center Groningen (UMCG), the
      Academic Medical Center Amsterdam (AMC), and the Princess Maxima Center Utrecht
      (PMC). Consecutive patients, aged 0-18 years, either diagnosed with B cell non
      Hodgkin lymphoma (B-NHL) or scheduled for autologous stem cell transplantation
      (SCT) between April 2015 and September 2016 were included in this study. In
      addition to the observational study in the Netherlands, an international online
      questionnaire was conducted for pediatric oncology centers. RESULTS: A total of
      13 patients were included, after 21 chemotherapy courses. No nutritional support
      was administered after 23.8% courses, tube feeding after 19.0% of the courses,
      TPN in 19.0% of courses, and 38.1% received a combination of tube feeding and
      TPN. The international survey revealed that 63.2% of the centers administered
      tube feeding as first choice, 31.6% administered only TPN as first choice, and
      one center administered a combination as first choice. CONCLUSIONS: There is a
      variability in feeding strategies in the clinical practice both in the
      Netherlands as well as worldwide. This study is a basis for future studies in
      this important clinical field to develop clinical trials comparing tube feeding
      and TPN both in adult and pediatric patients.

PMID- 28447224
TI  - Synchronous Neuroendocrine Carcinoma of Colon Presenting as Subacute Intestinal
      Obstruction-a Rare Case Report.

PMID- 28447221
TI  - Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset
      Alzheimer's disease.
AB  - Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub
      Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to
      high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High
      variability, however, is observed in downstream ABCA7 mRNA and protein
      expression, disease penetrance, and onset age, indicative of unknown modifying
      factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC
      mutations in a large early onset AD (EOAD)-control cohort, and examined the
      effect on transcript level with comprehensive third-generation long-read
      sequencing. We characterized the ABCA7 coding sequence with next-generation
      sequencing in 928 EOAD patients and 980 matched control individuals. With
      MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p
      = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten
      novel PTC mutations were only observed in patients, and PTC mutation carriers in
      general had an increased familial AD load. In addition, we observed nominal risk
      reducing trends for three common coding variants. Seven PTC mutations were
      further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore
      MinION platform. PTC-containing transcripts for each investigated PTC mutation
      were observed at varying proportion (5-41% of the total read count), implying
      incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and
      phased several previously unknown alternative splicing events (up to 30% of
      transcripts). In conjunction with PTC mutations, several of these novel ABCA7
      isoforms have the potential to rescue deleterious PTC effects. In conclusion,
      ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening
      of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed
      both varying degrees of NMD and transcript-modifying events, which may influence
      ABCA7 dosage, disease severity, and may create opportunities for therapeutic
      interventions in AD.

PMID- 28447225
TI  - Functional Interplay Between the Putative Measures of Rostral and Caudal Efferent
      Regulation of Speech Perception in Noise.
AB  - Efferent modulation has been demonstrated to be very important for speech
      perception, especially in the presence of noise. We examined the functional
      relationship between two efferent systems: the rostral and caudal efferent
      pathways and their individual influences on speech perception in noise. Earlier
      studies have shown that these two efferent mechanisms were correlated with speech
      perception in noise. However, previously, these mechanisms were studied in
      isolation, and their functional relationship with each other was not
      investigated. We used a correlational design to study the relationship if any,
      between these two mechanisms in young and old normal hearing individuals. We
      recorded context-dependent brainstem encoding as an index of rostral efferent
      function and contralateral suppression of otoacoustic emissions as an index of
      caudal efferent function in groups with good and poor speech perception in noise.
      These efferent mechanisms were analysed for their relationship with each other
      and with speech perception in noise. We found that the two efferent mechanisms
      did not show any functional relationship. Interestingly, both the efferent
      mechanisms correlated with speech perception in noise and they even emerged as
      significant predictors. Based on the data, we posit that the two efferent
      mechanisms function relatively independently but with a common goal of fine
      tuning the afferent input and refining auditory perception in degraded listening
      conditions.

PMID- 28447226
TI  - The Effects of Phonological Short-Term Memory and Speech Perception on Spoken
      Sentence Comprehension in Children: Simulating Deficits in an Experimental
      Design.
AB  - The roles of phonological short-term memory (pSTM) and speech perception in
      spoken sentence comprehension were examined in an experimental design. Deficits
      in pSTM and speech perception were simulated through task demands while typically
      developing children (N [Formula: see text] 71) completed a sentence-picture
      matching task. Children performed the control, simulated pSTM deficit, simulated
      speech perception deficit, or simulated double deficit condition. On long
      sentences, the double deficit group had lower scores than the control and speech
      perception deficit groups, and the pSTM deficit group had lower scores than the
      control group and marginally lower scores than the speech perception deficit
      group. The pSTM and speech perception groups performed similarly to groups with
      real deficits in these areas, who completed the control condition. Overall,
      scores were lowest on noncanonical long sentences. Results show pSTM has a
      greater effect than speech perception on sentence comprehension, at least in the
      tasks employed here.

PMID- 28447227
TI  - The efficacy of serratus anterior plane block in analgesia for thoracotomy: a
      retrospective study.
AB  - PURPOSE: A multimodal analgesic approach is necessary for post-thoracotomy pain,
      which can be severe. Intravenous access, central and peripheral nerve blocks are
      frequently used. The aim of this study was to evaluate the efficacy of serratus
      anterior plane block (SAPB) in the management of post-thoracotomy pain. METHODS:
      A total of 40 patients who underwent thoracotomy between January 2014 and January
      2016 were retrospectively analyzed. The patients were divided into two groups:
      Group M (intravenous patient-controlled analgesia morphine; n = 20) and Group S
      (intravenous patient-controlled analgesia morphine + SAPB; n = 20). The Visual
      Analogue Scale (VAS) was used for pain evaluation at the 1st, 2nd, 4th, 6th, 8th,
      12th and 24th postoperative hours and morphine consumption was evaluated at the
      6th, 12th and 24th postoperative hours. Secondary outcomes were additional
      analgesic requirement, side effects, the Ramsay Sedation Scale (RSS) scores,
      block onset time and block level. RESULTS: The VAS scores and the amount of
      morphine consumed at the 6th, 12th and 24th hours were found to be significantly
      lower in Group S than in Group M (P < 0.001). No statistically significant
      difference was found in the rate of side effects, including nausea, vomiting,
      pruritus, respiratory depression, bradycardia and hypotension, and RSS outcomes
      between the groups. CONCLUSION: Our study suggests that SAPB is an effective
      adjuvant treatment option for thoracotomy analgesia.

PMID- 28447230
TI  - What drives insurer participation and premiums in the Federally-Facilitated
      Marketplace?
AB  - We investigate determinants of market entry and premiums within the context of
      the Affordable Care Act's Marketplaces for individual insurance. Using Bresnahan
      and Reiss (1991) as the conceptual framework, we study how competition and firm
      heterogeneity relate to premiums in 36 states using Federally Facilitated or
      Supported Marketplaces in 2016. Our primary data source is the Qualified Health
      Plan Landscape File, augmented with market characteristics from the American
      Community Survey and Area Health Resource File as well as insurer-level
      information from federal Medical Loss Ratio annual reports. We first estimate a
      model of insurer entry and then investigate the relationship between a market's
      predicted number of entrants and insurer-level premiums. Our entry model results
      suggest that competition is increasing with the number of insurers, most notably
      as the market size increases from 3 to 4 entrants. Results from the premium
      regression suggest that each additional entrant is associated with approximately
      4% lower premiums, controlling for other factors. An alternative explanation for
      the relationship between entrants and premiums is that more efficient insurers
      (who can price lower) are the ones that enter markets with many entrants, and
      this is reflected in lower premiums. An exploratory analysis of insurers' non
      claims costs (a proxy for insurer efficiency) reveals that average costs among
      entrants are rising slightly with the number of insurers in the market. This
      pattern does not support the hypothesis that premiums decrease with more entrants
      because those entrants are more efficient, suggesting instead that the results
      are being driven mostly by price competition.

PMID- 28447229
TI  - Pathogenic role and therapeutic potential of pleiotrophin in mouse models of
      ocular vascular disease.
AB  - Angiogenic factors play an important role in the pathogenesis of diabetic
      retinopathy (DR), neovascular age-related macular degeneration (nAMD) and
      retinopathy of prematurity (ROP). Pleiotrophin, a well-known angiogenic factor,
      was recently reported to be upregulated in the vitreous fluid of patients with
      proliferative DR (PDR). However, its pathogenic role and therapeutic potential in
      ocular vascular diseases have not been defined in vivo. Here using corneal pocket
      assays, we demonstrated that pleiotrophin induced angiogenesis in vivo. To
      investigate the pathological role of pleiotrophin we used neutralizing antibody
      to block its function in multiple in vivo models of ocular vascular diseases. In
      a mouse model of DR, intravitreal injection of pleiotrophin-neutralizing antibody
      alleviated diabetic retinal vascular leakage. In a mouse model of oxygen-induced
      retinopathy (OIR), which is a surrogate model of ROP and PDR, we demonstrated
      that intravitreal injection of anti-pleiotrophin antibody prevented OIR-induced
      pathological retinal neovascularization and aberrant vessel tufts. Finally,
      pleiotrophin-neutralizing antibody ameliorated laser-induced choroidal
      neovascularization, a mouse model of nAMD, suggesting that pleiotrophin is
      involved in choroidal vascular disease. These findings suggest that pleiotrophin
      plays an important role in the pathogenesis of DR with retinal vascular leakage,
      ROP with retinal neovascularization and nAMD with choroidal neovascularization.
      The results also support pleiotrophin as a promising target for anti-angiogenic
      therapy.

PMID- 28447232
TI  - Distribution, seasonal variation and inhalation risks of polychlorinated dibenzo
      p-dioxins and dibenzofurans, polychlorinated biphenyls and polybrominated
      diphenyl ethers in the atmosphere of Beijing, China.
AB  - Spatial distribution, seasonal variation and potential inhalation risks of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated
      biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were investigated in
      the atmosphere of Beijing, using passive air samplers equipped with polyurethane
      foam disks. Concentrations of SigmaPCDD/Fs, SigmaPCBs and SigmaPBDEs ranged from
      8.4 to 179 fg WHO2005-TEQ/m3, 38.6-139 and 1.5-176 pg/m3, respectively. PCDFs
      showed higher air concentrations than those of PCDDs, indicating the influence of
      industrial activities and other combustion processes. The non-Aroclor congener,
      PCB-11, was detected in air (12.3-99.4 pg/m3) and dominated the PCB congener
      profiles (61.7-71.5% to ?PCBs). The congener patterns of PBDEs showed signatures
      from both penta-BDE and octa-BDE products. Levels of PCDD/Fs, PCBs and PBDEs at
      the industrial and residential sites were higher than those at rural site,
      indicating human activities in urban area as potential sources. Higher air
      concentrations of PCDD/Fs, PCBs and PBDEs were observed in summer, which could be
      associated with atmospheric deposition process, re-volatilization from soil
      surface and volatilization from use of technical products, respectively. Results
      of inhalation exposure and cancer risk showed that atmospheric PCDD/Fs, dioxin
      like PCBs and PBDEs did not cause high risks to the local residents of Beijing.
      This study provides further aid in evaluating emission sources, influencing
      factors and potential inhalation risks of the persistent organic pollutants to
      human health in mega-cities of China.

PMID- 28447231
TI  - The nutritional interrelationship between the growing and finishing phases in
      crossbred cattle raised in a tropical system.
AB  - This study evaluated the nutritional interrelationship between the growing and
      finishing phases of crossbred cattle in determining their performance. One
      hundred and eight animals were used (8 months old, body weight [BW] 211 +/- 20
      kg). During the dry season, the animals received one of the following
      supplements: a mineral plus urea supplement (ad libitum, MSD), a protein
      supplement (1 g/kg BW per day, PR1), or a protein-energy supplement (5 g/kg BW
      per day, PE). During the rainy season, the animals received one of the following
      supplements: a mineral without urea supplement (ad libitum, MSR), a protein
      supplement (1 g/kg BW per day, PR2), or PE (5 g/kg BW per day). The experimental
      design was completely randomized using a 3 * 3 factorial scheme (for the rainy
      season) and a 3 * 3 * 2 factorial scheme (for the finishing phase). The
      supplementation and finishing systems were considered to be the treatments, and
      the animals were considered to be the experimental units. Dry season
      supplementation did not affect the average daily gain (ADG) during the rainy
      season (P = 0.12) or the finishing phase (P = 0.73). An increase in the level of
      rainy season supplementation reduced ADG by 12% during the finishing phase (P <
      0.06). Providing PE during the dry and rainy seasons led to the animals being
      slaughtered 17 (P = 0.06) and 30 (P < 0.01) days earlier, respectively. Our
      results indicate that supplementation during the dry season (under poor-quality
      pasture conditions) does not affect the performance during the rainy season or
      the finishing phase. Furthermore, while providing PE during the rainy season can
      reduce ADG during finishing, the higher BW at the beginning of the finishing
      phase is sufficient to reduce the time of the finishing period.

PMID- 28447233
TI  - Total arsenic concentrations in Chinese children's urine by different geographic
      locations, ages, and genders.
AB  - Little is known about the variation of Chinese children's exposure to arsenic by
      geography, age, gender, and other potential factors. The main objective of this
      study was to investigate the total arsenic concentration in Chinese children's
      urine by geographic locations, ages, and genders. In total, 259 24-h urine
      samples were collected from 210 2- to 12-year-old children in China and analyzed
      for total arsenic and creatinine concentrations. The results showed that the
      upper limit (upper limit of the 90% confidence interval for the 97.5 fractile)
      was 27.51 ug/L or 55.88 ug/g creatinine for Chinese children. The total urinary
      arsenic levels were significantly different for children in Guangdong, Hubei, and
      Gansu provinces (P < 0.05), where the upper limits were 24.29, 58.70, and 44.29
      ug/g creatinine, respectively. In addition, the total urinary arsenic levels were
      higher for 2- to 7-year-old children than for 7- to 12-year-old children (P <
      0.05; the upper limits were 59.06 and 44.29 ug/g creatinine, respectively) and
      higher for rural children than for urban children (P < 0.05; the upper limits
      were 59.06 and 50.44 ug/g creatinine, respectively). The total urinary arsenic
      levels for boys were not significantly different from those for girls (P > 0.05),
      although the level for boys (the upper limit was 59.30 ug/g) was slightly higher
      than that for girls (the upper limit was 58.64 ug/g creatinine). Because the
      total urinary arsenic concentrations are significantly different for general
      populations of children in different locations and age groups, the reference
      level of total urinary arsenic might be dependent on the geographic site and the
      child's age.

PMID- 28447234
TI  - Remediation of soils contaminated with heavy metals with an emphasis on
      immobilization technology.
AB  - The major frequent contaminants in soil are heavy metals which may be responsible
      for detrimental health effects. The remediation of heavy metals in contaminated
      soils is considered as one of the most complicated tasks. Among different
      technologies, in situ immobilization of metals has received a great deal of
      attention and turned out to be a promising solution for soil remediation. In this
      review, remediation methods for removal of heavy metals in soil are explored with
      an emphasis on the in situ immobilization technique of metal(loid)s. Besides, the
      immobilization technique in contaminated soils is evaluated through the
      manipulation of the bioavailability of heavy metals using a range of soil
      amendment conditions. This technique is expected to efficiently alleviate the
      risk of groundwater contamination, plant uptake, and exposure to other living
      organisms. The efficacy of several amendments (e.g., red mud, biochar, phosphate
      rock) has been examined to emphasize the need for the simultaneous measurement of
      leaching and the phytoavailability of heavy metals. In addition, some amendments
      that are used in this technique are inexpensive and readily available in large
      quantities because they have been derived from bio-products or industrial by
      products (e.g., biochar, red mud, and steel slag). Among different amendments,
      iron-rich compounds and biochars show high efficiency to remediate multi-metal
      contaminated soils. Thereupon, immobilization technique can be considered a
      preferable option as it is inexpensive and easily applicable to large quantities
      of contaminants derived from various sources.

PMID- 28447235
TI  - Prevalence of musculoskeletal diseases in a semi-urban Nigerian community:
      results of a cross-sectional survey using COPCORD methodology.
AB  - The International League of Associations for Rheumatology (ILAR) in collaboration
      with the World Health Organization (WHO) initiated the Community Oriented Program
      for the Control of Rheumatic diseases (COPCORD) to promote the growth of
      rheumatology in developing countries. This is the first COPCORD-type survey
      carried out in a West African community. The objective of this study was to
      determine the prevalence of musculoskeletal diseases in a semi-urban Nigerian
      community, using the COPCORD methodology. This is a cross-sectional total
      population survey, carried out in Katon Rikkos, Jos, Nigeria, from June 2015 to
      November 2016. All inhabitants of the community who are 15 years and older were
      included in the study, except those who were not available or refused to
      participate. Trained health workers from the community carried out a house-to
      house survey, to administer the COPCORD questionnaire. People reporting
      musculoskeletal symptoms were examined and investigated at the teaching hospital,
      to determine the specific type of musculoskeletal diseases. Data was analyzed
      using Epi-info version 7.1.5 and P values of <0.05 were considered statistically
      significant. The median age of the study population was 33 (IQR 24-46) years,
      with a male to female ratio of 1:1.1. The prevalence of musculoskeletal disease
      was 33%. Females (57.0%) were more affected than males (43.0%); the most common
      form of musculoskeletal diseases diagnosed was osteoarthritis (22.0%). Male sex
      and a family history of musculoskeletal diseases were independent predictors of
      musculoskeletal diseases. A Health Assessment Questionnaire Disability Index (HAQ
      DI) >=1 was recorded in 14% of subjects with musculoskeletal diseases. The
      prevalence of musculoskeletal diseases in this community is high with significant
      disability; therefore, there is urgent need for increased access to rheumatology
      care in the community.

PMID- 28447236
TI  - The history of an unknown dermatological wax collection from Cluj-Napoca
      University "Iuliu Hatieganu", Romania.
AB  - Among the dermatological wax collections across Europe, one of the latest created
      is the collection from Cluj-Napoca University, Romania. The initiator was
      Professor Coriolan Tataru and the moulage artist employed was Dr. Richard
      Hoffmann. Between the years 1923 and 1928, around 200 wax moulages were made, all
      realised after patients hospitalised in the clinic. The majority of cases
      represent the dermatological infectious pathology of that time: syphilis,
      cutaneous tuberculosis and mycetomas. Other interesting moulages represent
      genodermatoses, pelagra, different cutaneous cancers, and atypical aspects of
      common diseases like psoriasis and eczemas. The models depicting different stages
      of syphilis won the gold medal at the Ninth International Congress of Dermato
      Venereology held in Budapest in 1935. We believe that the collection has a great
      value from a historical, artistic, didactic and scientific point of view, and it
      is organised as a museum within the Dermatology Clinic.

PMID- 28447238
TI  - Effects of hepatitis C virus infection on the safety of chemotherapy for breast
      cancer patients.
AB  - PURPOSE: Hepatitis C virus (HCV) is one of the major pathogens of chronic viral
      hepatitis, and approximately 38 million patients are infected with HCV in China.
      However, little information is available on the effect of HCV infection during
      chemotherapy for breast cancer and the impact of HCV infection on the toxicity of
      chemotherapy and targeted therapy. METHODS: We performed a retrospective survey
      of 835 patients who were diagnosed with breast cancer between January 2010 and
      December 2015 at our institution. All patients had been screened for HCV
      infection at the time of breast cancer diagnosis. We retrospectively investigated
      the toxicities of chemotherapy and the changes in HCV load based on a review of
      the medical records. RESULTS: A total of 21 patients with positive anti-HCV
      antibody tests received chemotherapy. The median patient age was 46.3 +/- 11.2
      years. Four (19.0%) patients exhibited abnormal liver function at baseline. The
      morbidity of abnormal liver function at baseline was higher in HCV-infected
      patients (19.0% vs. 0, P = 0.000). Four patients received trastuzumab therapy.
      Five (23.8%) patients who received chemotherapy developed hepatitis. No patients
      presented with HCV reactivation. The morbidity of hepatitis and the rate of
      disruption of chemotherapy were not significantly different between breast cancer
      patients without HCV infection and those with HCV infection (23.8 vs. 14.2% P =
      0.342, 9.5 vs. 5.0% P = 0.619, respectively). CONCLUSION: HCV infection had no
      adverse impact on chemotherapy in breast cancer patients. However, consulting a
      gastroenterologist and closely monitoring liver function during the course of
      chemotherapy may benefit patients.

PMID- 28447239
TI  - The potential role of three-dimensional surface imaging as a tool to evaluate
      aesthetic outcome after Breast Conserving Therapy (BCT).
AB  - PURPOSE: To establish whether objective measurements of symmetry of volume and
      shape using three-dimensional surface imaging (3D-SI) can be used as surrogate
      markers of aesthetic outcome in patients who have undergone breast conserving
      therapy (BCT). METHODS: Women who had undergone unilateral BCT in the preceding 1
      6 years were invited to participate. Participants completed a satisfaction
      questionnaire (BREAST-Q) and underwent 3D-SI. Volume and surface symmetry were
      measured on the images. Assessment of aesthetic outcome was undertaken by a panel
      of clinicians. The Kruskal-Wallis test was used to assess the relationship
      between volume and shape symmetry measurements with the panel score. Spearman's
      rho correlations were used to assess the relationship between the measurements
      and patient satisfaction. RESULTS: 200 women participated. Median volume symmetry
      was 87% (IQR 78-93) and shape symmetry was 5.9 mm (IQR 4.2-8.0). The participants
      were grouped according to panel assessment of aesthetic outcome (poor, fair,
      good, excellent) and the median volume and shape symmetry was calculated for each
      group. Volume symmetry significantly differed between the groups. Post hoc
      pairwise comparisons demonstrated that these differences existed between panel
      scores of fair versus good and good versus excellent. Median shape symmetry also
      differed according to patient panel groups with four significant pairwise
      comparisons between poor versus good, poor versus excellent, fair versus good and
      fair versus excellent. There was a significant but weak correlation of both
      volume symmetry and surface asymmetry with BREAST-Q scores (correlation
      coefficients 0.187 and -0.229, respectively). CONCLUSION: Breast volume and shape
      symmetry are both associated with panel assessment scores and patient
      satisfaction. The objective volume and shape symmetry measures were strongly
      associated with panel assessment scores, such that a 3D-SI tool could replace
      panel assessment as a faster and more objective method of evaluating aesthetic
      outcomes.

PMID- 28447237
TI  - Effects of metformin versus placebo on vitamin B12 metabolism in non-diabetic
      breast cancer patients in CCTG MA.32.
AB  - BACKGROUND: Metformin is associated with low levels of vitamin B12 (VitB12) in
      patients with diabetes. The CCTG/MA.32 trial investigates the effects of
      metformin vs placebo on breast cancer (BC) outcomes in non-diabetic high-risk BC
      patients. We analyzed VitB12 at baseline and after 6 months of metformin (versus
      placebo) in the first 492 patients with paired blood samples. METHODS: VitB12 was
      analyzed centrally in baseline and 6-month fasting plasma. Levels <181 pmol/L
      were considered deficient, 181-221 pmol/L borderline, and >=222 pmol/L
      sufficient. Methylmalonic acid (MMA) and homocysteine (HC) were assayed in those
      with VitB12 levels <222 pmol/L. Statistical analyses used Spearman's rank
      correlation coefficients and Wilcoxon signed-rank test for continuous variables
      and Chi-square test for categorical variables. RESULTS: 237 patients received
      metformin and 255 received placebo; median (inter quartile range) baseline VitB12
      levels were 390 (290, 552) and 370 (290, 552) pmol/L in the metformin and placebo
      arms, respectively (p = 0.97). At 6 months, the median levels were 320 (244, 419)
      in the metformin versus 380 (286, 546) pmol/L in the placebo arm (p = 0.0001). At
      baseline, 15 patients (11 metformin and 4 placebo) had VitB12 <181 pmol/L, and at
      6 months, 18 patients (15 metformin and 3 placebo) (p = 0.004). Median hemoglobin
      was similar at baseline, metformin, 130 g/L (124-137), and placebo arms, 131 g/L
      (124-137) (p = 0.38), and at 6 months, metformin, 131 g/L (91-162), and 131 g/L
      (106-169) in placebo group (p = 0.11). Of the 74 subjects with vitamin B12 <222
      pmol/L at either time point (45 metformin, 29 placebo), at baseline MMA was
      normal in all patients and two had elevated HC (>15MUmol/L). At 6 months, one
      patient (metformin) had MMA >0.4MUmol/L and 3 (2 metformin, 1 placebo) had HC >
      15MUmol/L. CONCLUSIONS: There was an increased rate of biochemical VitB12
      deficiency after 6 months of metformin; this was not associated with anemia.
      Further research will investigate VitB12 levels in all subjects at baseline and
      at 6 and 60 months.

PMID- 28447240
TI  - Relationship between IHC4 score and response to neo-adjuvant chemotherapy in
      estrogen receptor-positive breast cancer.
AB  - AIMS: To determine whether IHC4 score assessed on pre-treatment core biopsies (i)
      predicts response to neo-adjuvant chemotherapy in ER-positive (ER+) breast
      cancer; (ii) provides more predictive information than Ki67 alone. METHODS: 113
      patients with ER+ primary breast cancer treated with neo-adjuvant chemotherapy at
      the Royal Marsden Hospital between 2002 and 2010 were included in the study.
      Pathologic assessment of the excision specimen was made for residual disease.
      IHC4 was determined on pre-treatment core biopsies, blinded to clinical outcome,
      by immunohistochemistry using quantitative scoring of ER (H-score), PgR (%) and
      Ki67 (%). Determination of HER2 status was made by immunohistochemistry and
      fluorescent in situ hybridization for 2+ cases. IHC4 and Ki67 scores were tested
      for their association with pathological complete response (pCR) rate and residual
      cancer burden (RCB) score. RESULTS: 18 (16%) of the 113 patients and 8 (9%) of
      the 88 HER2-ve cases achieved pCR. Ki67 and IHC4 score were both positively
      associated with achievement of pCR (P < 10-7 and P < 10-9, respectively) and
      RCB0+1 (P < 10-5 and P < 10-9, respectively) following neo-adjuvant chemotherapy
      in all patients. Rates of pCR+RCB1 were 45 and 66% in the highest quartiles of
      Ki67 and IHC4 scores, respectively. In ER+HER2-ve cases, pCR+RCB1 rates were 35%
      and in the highest quartile of both Ki67 and IHC4. There were no pCRs in the
      lower half of IHC4 or Ki67 scores. CONCLUSIONS: IHC4 was strongly predictive of
      pCR or near pCR in ER+ breast cancers following neo-adjuvant chemotherapy. Ki67
      was an important component of this predictive ability, but was not as predictive
      as IHC4.

PMID- 28447241
TI  - Abbreviated breast dynamic contrast-enhanced MR imaging for lesion detection and
      characterization: the experience of an Italian oncologic center.
AB  - BACKGROUND: To evaluate the performance of an abbreviated dynamic contrast
      enhanced MR imaging (MRI) protocol for breast cancer detection; a comparison with
      the complete diagnostic protocol has been conducted. METHODS: A retrospective
      analysis on 508 patients was performed. Abbreviated protocol (AP) included one
      pre-contrast and the first post-contrast T1-weighted series. Complete protocol
      (CP) consisted of four post-contrast and one pre-contrast T1-weighted series.
      Diagnostic performance was assessed for AP and CP. Performance comparison was
      made using McNemar's test for sensitivity and specificity and Moskowitz and
      Pepe's method as regards negative predictive value (NPV) and positive predictive
      value (PPV). AP has been realized in two different ways (AP1 and AP2) and they
      were compared by means of Cohen's kappa. RESULTS: Both CP and AP revealed 206 of
      207 cancers. There were no statistically significant differences between AP and
      CP diagnostic performance (P > 0.05). NPVs of CP and both versions of AP (99.57
      vs. 99.56%, P = 0.39), as well as the specificity (77.08 vs. 75.42%, P = 0.18),
      were substantially equivalent. Relative predictive value method did not reveal
      the presence of a statistically significant difference between the PPV of CP and
      both versions of AP (74.91 vs. 73.57%, P = 0.099). Analysis for single lesion
      confirmed that both CP and AP had equivalent results: CP and AP revealed 280 of
      281 malignancies. NPVs of CP and both AP versions, as well as the specificity (P
      > 0.05), were substantially equivalent. Relative predictive value method did not
      reveal the presence of a significant difference between the PPV of CP and both AP
      versions (70.89 vs. 70.18%, P = 0.25; 70.89 vs. 70.00%, P = 0.13). CONCLUSIONS:
      Abbreviated approach to breast MRI examination reduces the image acquisition and
      the reading time associated with MR substantially without influencing the
      diagnostic accuracy (high sensitivity and NPV >99.5%). AP could translate into
      cost-savings and could enable a higher number of examinations within the same MR
      session.

PMID- 28447242
TI  - Testing the online reading effects of emotionality on relative clause attachment.
AB  - Previous research has shown the impact of the emotional dimension of nouns (i.e.,
      valence and arousal) on the completion of relative clauses (RC) that are preceded
      by a double antecedent [e.g.,: Someone shot the servant (the first noun phrase,
      NP1) of the actress (the second noun phrase, NP2) who was on the balcony] (Fraga
      et al. in Q J Exp Psychol 65:1740-1759, 2012). The present study explored for the
      first time the role of emotional valence, specifically emotional positive nouns,
      on RC disambiguation in a self-paced reading experiment. Two types of NP1-NP2
      relationships were compared: emotional-neutral vs. neutral-emotional. Results
      showed NP1 preferences in the emotional-neutral condition, whereas no preferences
      were found in the neutral-emotional condition. We conclude that during reading,
      the emotional properties of nouns play a role in disambiguation preferences: RC
      attachment preferences can be neutralized when emotional factors are manipulated.
      The results are discussed within the framework of current models of sentence
      processing and with reference to the controversial differences between
      comprehension and production.

PMID- 28447243
TI  - The Longitudinal Association of Relationship Quality and Reoffending Among First
      Time Juvenile Offenders and Their Mothers.
AB  - To understand how youth desist from crime after their first arrest, it is
      necessary to investigate their primary support system: their parents. As such,
      this study examined the reciprocal effects of justice system contact on the
      mother-child dyad. Interviews with 317 mothers and their sons from Orange County,
      CA, Jefferson Parish, LA, and Philadelphia, PA were conducted semiannually over
      two and a half years. At the beginning of the study, the sons were first-time
      offenders aged 13-17 and mostly non-White (i.e., 19.2 White, 56.5 Latino, 21.5
      Black, and 2.8% another race/ethnicity). The results revealed that a high quality
      initial mother-son relationship reduces youths' re-offending over time.
      Furthermore, as mothers perceived that their sons were offending more, they
      reported less warmth in their relationships with their sons two and a half years
      later. Interestingly, youth's age emerged as a moderator. First, older youth were
      less likely to engage in reoffending if they had a warm maternal relationship.
      Second, decreases in relationship warmth associated with re-offending were
      steeper for younger youth. The findings have implications for juvenile justice
      policy in terms of improving probationary outcomes for youth offenders, and
      alleviating the financial and emotional burden on justice system-involved
      families.

PMID- 28447245
TI  - Neuroanatomical variations as a function of experience in a complex daily task: A
      VBM and DTI study on driving experience.
AB  - Complex tasks require the learning and integration of multiple cognitive,
      sensory, and psychomotor skills for correct execution. Driving-related skills are
      developed step by step through the increase of mileage driven and the
      accumulation of practice in different traffic situations. The acquisition of
      these skills should be reflected in the brain structure. However, no previous
      studies have explored brain structural variations associated with driving
      experience. The aim of the present study was to investigate whether driving
      frequency, defined as average annual driving mileage, is related to
      neuroanatomical variations in gray matter (GM) volume and white matter (WM)
      integrity using voxel-based morphometry (VBM) and DTI-based fractional anisotropy
      (FA), respectively. We recruited 83 drivers with variable range of annual driving
      mileage and controlled for age, sex, handedness, IQ, time since the acquisition
      of driving license, use of motorcycles/mopeds and bicycles, perceived driving
      skills, and subjective probability of having an accident. Our results showed
      variations in white matter FA as a function of mileage driven. Driving experience
      was related to a significant increase of FA in parts of the right hemisphere
      superior and inferior longitudinal fasciculus, anterior thalamic radiation,
      forceps majors, inferior fronto-occipital fasciculus, and corticospinal tract. No
      significant differences were observed in gray matter volumes. FA variations were
      found in brain regions that have been associated with cognitive, visual, and
      motor processes necessary for skilled performance in driving. These results
      suggest that variations in white matter diffusivity can underlie the development
      of driving skills and safer driving.

PMID- 28447246
TI  - Brain size bias compensated graph-theoretical parameters are also better in
      women's structural connectomes.

PMID- 28447244
TI  - Retinal vein occlusion and paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder associated with
      increased risk for thrombosis and reduced life expectancy. Retinal vein occlusion
      (RVO) is a frequent cause of vision loss but its relationship with PNH has not
      been studied systematically. Patients followed up for RVO in our ophthalmology
      department were screened for the presence of a PNH clone in peripheral blood by
      means of flow cytometry. The presence of other well-documented risk factors for
      RVO was also analyzed. In a series of 110 patients (54 males, median age of 67)
      we found no evidence of PNH. Most patients (97/110) had cardiovascular risk
      factors and/or hyperhomocysteinemia (67/110). Inherited thrombophilias were rare
      (three confirmed cases). Therefore, PNH does not appear to play a role in the
      development of RVO. However, this finding does not necessarily apply to young
      patients and/or those with no conventional risk factors for RVO, due to the low
      number of patients in these subgroups in our population.

PMID- 28447247
TI  - The Role of Peripheral Myelin Protein 2 in Remyelination.
AB  - The protein component of the myelin layer is essential for all aspects of
      peripheral nerves, and its deficiency can lead to structural and functional
      impairment. The presence of peripheral myelin protein 2 (P2, PMP2, FABP8, M-FABP)
      in Schwann cells has been known for decades and shown recently to be involved in
      the lipid homeostasis in the peripheral neural system. However, its precise role
      during de- and remyelination has yet to be elucidated. To this end, we assessed
      remyelination after sciatic nerve crush injury in vivo, and in an experimental
      de/remyelination ex vivo myelinating culture model in P2-deficient (P2 -/- ) and
      wild-type (WT) animals. In vivo, the nerve crush paradigm revealed temporal
      structural and functional changes in P2 -/- mice as compared to WT animals.
      Concomitantly, P2 -/- DRG cultures demonstrated the presence of shorter
      internodes and enlarged nodes after ex vivo de/remyelination. Together, these
      data indicate that P2 may play a role in remyelination of the injured peripheral
      nervous system, presumably by affecting the nodal and internodal configuration.

PMID- 28447248
TI  - Somatic SETBP1 mutations in myeloid neoplasms.
AB  - SETBP1 is a SET-binding protein regulating self-renewal potential through HOXA
      protein activation. Somatic SETBP1 mutations were identified by whole exome
      sequencing in several phenotypes of myelodysplastic/myeloproliferative neoplasms
      (MDS/MPN), including atypical chronic myeloid leukemia, chronic myelomonocytic
      leukemia, and juvenile myelomonocytic leukemia as well as in secondary acute
      myeloid leukemia (sAML). Surprisingly, its recurrent somatic activated mutations
      are located at the identical positions of germline mutations reported in
      congenital Schinzel-Giedion syndrome. In general, somatic SETBP1 mutations have a
      significant clinical impact on the outcome as poor prognostic factor, due to
      downstream HOXA-pathway as well as associated aggressive types of chromosomal
      defects (-7/del(7q) and i(17q)), which is consistent with wild-type SETBP1
      activation in aggressive types of acute myeloid leukemia and leukemic evolution.
      Biologically, mutant SETBP1 attenuates RUNX1 and activates MYB. The studies of
      mouse models confirmed biological significance of SETBP1 mutations in myeloid
      leukemogenesis, particularly associated with ASXL1 mutations. SETBP1 is a major
      oncogene in myeloid neoplasms, which cooperates with various genetic events and
      causes distinct phenotypes of MDS/MPN and sAML.

PMID- 28447249
TI  - Guest Editorial: Understanding of MPN and MDS/MPN based on molecular pathogenesis
      and clinical aspects.

PMID- 28447251
TI  - Psychiatric and neurologic lessons in the oldest Persian medical liber.
      Akhawayani Bokhari (?-died 983 AD), physician of insane.

PMID- 28447250
TI  - Parent-reported cognitive function is associated with leukoencephalopathy in
      children with brain tumors.
AB  - PURPOSE: Cognitive dysfunction is a major concern for children with brain tumors.
      A valid, user-friendly screening tool could facilitate prompt referral for
      comprehensive neuropsychological assessments and therefore early intervention.
      Applications of the pediatric perceived cognitive function item bank (pedsPCF)
      such as computerized adaptive testing can potentially serve as such a tool given
      its brevity and user-friendly nature. This study aimed to evaluate whether
      pedsPCF was a valid indicator of cerebral compromise using the criterion of
      structural brain changes indicated by leukoencephalopathy grades. METHODS: Data
      from 99 children (mean age = 12.6 years) with brain tumors and their parents were
      analyzed. Average time since diagnosis was 5.8 years; time since last treatment
      was 4.3 years. Leukoencephalopathy grade (range 0-4) was based on white matter
      damage and degree of deep white matter volume loss shown on MRI. Parents of
      patients completed the pedsPCF. Scores were based on the US general population
      based T-score metric (mean = 50; SD = 10). Higher scores reflect better function.
      RESULTS: Leukoencephalopathy grade distributions were as follows: 36 grade 0, 27
      grade 1, 22 grade 2, 13 grade 3, and 1 grade 4. The mean pedsPCF T-score was 48.3
      (SD = 8.3; range 30.5-63.7). The pedsPCF scores significantly discriminated
      patients with different leukoencephalopathy grades, F = 4.14, p = 0.0084. Effect
      sizes ranged from 0.09 (grade 0 vs. 1) to 1.22 (grade 0 vs. 3/4). CONCLUSION:
      This study demonstrates that the pedsPCF is a valid indicator of
      leukoencephalopathy and provides support for its use as a screening tool for more
      comprehensive neurocognitive testing.

PMID- 28447252
TI  - A preliminary study for conducting a rational assessment of radon exposure
      levels.
AB  - The aim of this study was to determine the factors that go into a highly reliable
      estimate of radon exposure levels for use in setting up the case-control study.
      To this end, the present study conducted a multi-faceted investigation of the
      distribution of radon concentrations in the bedrooms and living rooms of 400
      households in the target areas during the winter months from December 2014 to
      February 2015. We determined that taking the mean value of the radon
      concentration levels detected in the bedroom and living room as the
      representative value of residential concentration is appropriate, given the
      usability of previous research data and the difference in the concentration
      levels between the two. In terms of detector placement, we found that detectors
      should not inconvenience residents or be affected by an air current. Further, we
      found that housing type should distinguish between regular housing (single
      detached, row, and multiplex housing) and apartments but that the building type
      was not a key factor in the assessment of radon exposure levels. Houses should be
      classified into those constructed with soil (red clay) and those with constructed
      with general building materials for the assessment of radon exposure levels.

PMID- 28447254
TI  - The effect of an online referral system on referrals to bariatric surgery.
AB  - BACKGROUND: The Ontario Bariatric Network implemented an online referral system
      to completely replace a fax-based system in 2015. Strategies such as electronic
      information transfer have been suggested to improve the bariatric referral
      process but few studies exist demonstrating their efficacy. Therefore, the
      purpose of this study was to determine the impact on referral rates to bariatric
      surgery after converting to an online referral system from a fax-based system.
      METHODS: All referrals from 2011 to 2015 were included in the study. The main
      outcomes included the total number of referrals and whether a practitioner
      increased referrals after the implementation of the online referral system. A
      hierarchical logistic regression model was used for the final analysis.
      Predictors of interest included physician and neighbourhood level factors
      RESULTS: Referrals more than doubled overall and increased significantly across
      all health regions. Compared to practitioners in their first five years, all
      other experience groups were approximately 50% less likely to increase referrals.
      Compared to those within 50 km of a bariatric facility, practitioners 50-99 km
      (OR 0.76 95% CI 0.58-0.98 p = 0.04) and 100-199 km (OR 0.73 95% CI 0.55-0.96 p =
      0.03) away were both significantly less likely to increase referrals. CONCLUSION:
      This study found that referrals increased significantly after implementing an
      online referral system. Furthermore, physicians in their first five years of
      practice as well as those practicing closer to bariatric centers were more likely
      to increase referrals. Our findings demonstrate that an online referral system
      may aid in increasing referrals to bariatric surgery.

PMID- 28447253
TI  - An insight into mercury reduction process by humic substances in aqueous medium
      under dark condition.
AB  - Mercury (Hg) reduction by humic substances (HS) in the aquatic medium under the
      dark condition is a poorly understood but important process in Hg biogeochemical
      cycling. In this study, an effort was made to provide a better understanding of
      Hg(II) reduction by well-characterized humic substances under dark condition.
      Reduction of Hg(II) by dissolved HS in aquatic systems increases with increasing
      Hg loading. However, Hg(II) reduction gradually decreases with the increasing
      total S content and oxygen containing functional groups in the dissolved HS under
      dark condition. Increasing major cation concentration decreases the rate of
      Hg(II) reduction in aquatic systems. High concentration of Ca2+ ion slows down
      the intermolecular electron transfer from HS to Hg(II) and inhibits the formation
      of Hg0 in absence of light. This study indicates that complexation of Hg(II) and
      HS is essential for Hg reduction under dark condition.

PMID- 28447255
TI  - Phenolic Compounds, Volatiles and Antioxidant Capacity of White Myrtle Berry
      Liqueurs.
AB  - The aim of this research was to evaluate the antioxidant capacity and physical
      chemical characteristics of commercial white myrtle berry (Myrtus communis L.
      var. leucocarpa DC) liqueur (WMBL). The total phenolic (TP) content was measured
      spectrophotometrically, applying a modified Folin-Ciocalteu's method, and
      phenolic compounds were identified by high-performance liquid chromatography
      (HPLC) coupled with electrospray mass spectrometry, and quantified by HPLC
      coupled with ultraviolet/visible detection. The antioxidant capacities were
      evaluated by FRAP, CUPRAC, DPPH*, and ABTS*+ assays. The volatiles were assessed
      by gas chromatography and mass spectrometry (GC-MS/FID) after headspace solid
      phase microextraction (HS-SPME) and liquid-liquid extraction (LLE). WMBL showed
      lower TP levels (636.3 +/- 39.2 mg GAE/L) than in purple myrtle berry liqueur
      (PMBL). Nevertheless, WMBL exhibited better antioxidant capacities, potentially
      due to high concentrations of gallic acid (294.2 +/- 14.2 mg/L) and its
      derivatives (58.3 +/- 2.1 mg/L). Other phenolic compounds detected by HPLC-DAD
      and LC-MS/MS were flavonols like myricetin and its derivatives (myricetin-3-O
      galactoside and myricetin-3-O-rhamnoside) with concentrations similar to those
      found in PMBL. GC-MS/FID analysis revealed 44 compounds (terpenes, higher
      aliphatic compounds and shikimic acid pathway derivatives). 1,8-Cineole was the
      most abundant terpene in the liqueur (26.5% (HS-SPME) and 9.6% (LLE)).

PMID- 28447258
TI  - I spy with my MRI: Cause of complete heart block in a young patient revealed.

PMID- 28447256
TI  - Establishment of a protocol to extend the lifespan of human hormone-secreting
      pituitary adenoma cells.
AB  - PURPOSE: The aim of this study was to generate immortalized human anterior
      pituitary adenoma cells. Reliable cell models for the study of human pituitary
      adenomas are as yet lacking and studies performed so far used repeated passaging
      of freshly excised adenomas, with the attendant limitations due to limited
      survival in culture, early senescence, and poor reproducibility. METHODS &
      RESULTS: We devised a technique based upon repeated co-transfections of two
      retroviral vectors, one carrying the catalytic subunit of human telomerase,
      hTERT, the other SV40 large T antigen. This approach extended the lifespan of
      cells derived from a human growth hormone-secreting adenoma up to 18 months while
      retaining morphology of primary cells, growth hormone synthesis and growth
      hormone secretion. CONCLUSIONS: Our attempt represents the first demonstration of
      successful lifespan extension of human growth hormone-secreting pituitary adenoma
      cells via co-transfection of hTERT and SV40T and paves the way to future attempts
      to obtain stable cell lines.

PMID- 28447259
TI  - Adequate sensing of ventricular fibrillation?

PMID- 28447260
TI  - Adequate sensing of ventricular fibrillation?

PMID- 28447257
TI  - Recent developments in radiotherapy for small-cell lung cancer: a review by the
      Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology
      Society).
AB  - Small-cell lung cancer (SCLC) accounts for 13% of all lung tumours. The standard
      treatment in patients with limited-stage disease is radiotherapy combined with
      chemotherapy. In extensive SCLC, the importance of consolidation thoracic
      radiotherapy in patients with a good treatment response has become increasingly
      recognized. In both limited and extensive disease, prophylactic cranial
      irradiation is recommended in patients who respond to treatment. New therapeutic
      approaches such as immunotherapy are being increasingly incorporated into the
      treatment of SCLC, although more slowly than in non-small cell lung cancer
      (NSCLC). Diverse radiation dose and fractionation schemes, administered in
      varying combinations with these new drugs, are being investigated. In the present
      study we review and update the role of radiotherapy in the treatment of SCLC. We
      also discuss the main clinical trials currently underway in order to identify
      future trends.

PMID- 28447261
TI  - A surprising finding after adenosine administration.

PMID- 28447262
TI  - A surprising finding after adenosine administration.

PMID- 28447264
TI  - Erratum to: The exciting "bench to bedside" journey of cell therapies for acute
      kidney injury and renal transplantation.

PMID- 28447263
TI  - Design of a Lentiviral Vector for the Inducible Expression of MYC: A New Strategy
      for Construction Approach.
AB  - Lentiviral vectors are powerful tools for gene expression studies. Here we report
      the construction of pTIJ, a vector for inducible gene expression. pTIJ was
      generated from pTRIPZ backbone, which is designed for the inducible expression of
      shRNA sequences, by the introducing of a multiple cloning site upstream of the
      Tet promoter and the removal of miR30 flanking sequences. To evaluate pTIJ as a
      tool for the inducible expression of genes of interest, we introduced MYC cDNA
      into pTIJ and infected two small cell lung cancer cell lines, H209 and H345.
      Induction of MYC expression by doxycycline was detectable in both cell lines by
      real-time PCR and western blot analysis. This study highlights the relevance of
      pTIJ vector to allow the inducible expression of any gene of interest. In our
      belief, pTIJ will be an extremely useful tool to simplify the generation of
      genetically engineered cell lines for the inducible expression of cDNA sequences
      in biological studies. Furthermore, we report the generation of a pTIJ-MYC vector
      for the inducible expression of the oncogene MYC.

PMID- 28447265
TI  - NADP+-dependent isocitrate dehydrogenase from a psychrophilic bacterium,
      Psychromonas marina.
AB  - The gene encoding NADP+-dependent isocitrate dehydrogenase (IDH; EC 1.1.1.42) of
      a psychrophilic bacterium, Psychromonas marina, was cloned and sequenced. The
      open reading frame of the gene encoding IDH of P. marina (PmIDH) was 2229 bp in
      length and corresponded to a polypeptide composed of 742 amino acids. The
      molecular mass of IDH was calculated as 80,426 Da. The deduced amino acid
      sequence of PmIDH exhibited high degrees of homology with the monomeric IDH from
      other bacteria such as Colwellia maris (62% identity) and Azotobacter vinelandii
      (AvIDH) (64%). His-tagged PmIDH overexpressed in Escherichia coli cells was
      purified and characterized. The optimum temperature of PmIDH activity was about
      35  degrees C; however, the enzyme lost 74% of the activity after incubation for
      10 min at 30  degrees C, indicating that this enzyme is thermolabile. Chimeric
      enzymes produced through domain swapping between PmIDH and mesophilic AvIDH were
      constructed and their optimum temperatures and thermostability were determined.
      The results suggest that regions 2 and 3, especially region 3, of the two IDHs
      are involved in their catalytic activities and optimum temperature and
      thermostability for activity.

PMID- 28447266
TI  - In-depth characterization of bacterial and archaeal communities present in the
      abandoned Kettara pyrrhotite mine tailings (Morocco).
AB  - In Morocco, pollution caused by closed mines continues to be a serious threat to
      the environment, like the generation of acid mine drainage. Mine drainage is
      produced by environmental and microbial oxidation of sulfur minerals originating
      from mine wastes. The fundamental role of microbial communities is well known,
      like implication of Fe-oxidizing and to a lesser extent S-oxidizing microorganism
      in bioleaching. However, the structure of the microbial communities varies a lot
      from one site to another, like diversity depends on many factors such as
      mineralogy, concentration of metals and metalloids or pH, etc. In this study,
      prokaryotic communities in the pyrrhotite-rich tailings of Kettara mine were
      characterized using the Illumina sequencing. In-depth phylogenetic analysis
      revealed a total of 12 phyla of bacteria and 1 phyla of Archaea. The majority of
      sequences belonged to the phylum of Proteobacteria and Firmicutes with a
      predominance of Bacillus, Pseudomonas or Corynebacterium genera. Many microbial
      populations are implicated in the iron, sulfur and arsenic cycles, like
      Acidiferrobacter, Leptospirillum, or Alicyclobacillus in Fe; Acidiferrobacter and
      Sulfobacillus in S; and Bacillus or Pseudomonas in As. This is one of the first
      description of prokaryotic communities in pyrrhotite-rich mine tailings using
      high-throughput sequencing.

PMID- 28447267
TI  - Erratum to: The Rituximab Biosimilar CT-P10 in Rheumatology and Cancer: A Budget
      Impact Analysis in 28 European Countries.

PMID- 28447269
TI  - Estimating HIV Medication Adherence and Persistence: Two Instruments for Clinical
      and Research Use.
AB  - Antiretroviral therapy (ART) requires lifelong daily oral therapy. While patient
      characteristics associated with suboptimal ART adherence and persistence have
      been described in cohorts of HIV-infected persons, these factors are poor
      predictors of individual medication taking behaviors. We aimed to create and test
      instruments for the estimation of future ART adherence and persistence for
      clinical and research applications. Following formative work, a battery of 148
      items broadly related to HIV infection and treatment was developed and
      administered to 181 HIV-infected patients. ART adherence and persistence were
      assessed using electronic monitoring for 3 months. Perceived confidence in
      medication taking and self-reported barriers to adherence were strongest in
      predicting non-adherence over time. Barriers to adherence (e.g., affordability,
      scheduling) were the strongest predictors of non-adherence, as well as 3- and 7
      day non-persistence. A ten-item battery for prediction of these outcomes (
      www.med.unc.edu/ncaidstraining/adherence/for-providers ) and a 30-item battery
      reflective of underlying psychological constructs can help identify and study
      individuals at risk for suboptimal ART adherence and persistence.

PMID- 28447268
TI  - Atypical age-dependency of executive function and white matter microstructure in
      children and adolescents with autism spectrum disorders.
AB  - Executive function (EF) performance is associated with measurements of white
      matter microstructure (WMS) in typical individuals. Impaired EF is a hallmark
      symptom of autism spectrum disorders (ASD) but it is unclear how impaired EF
      relates to variability in WMS. Twenty-one male youth (8-18 years) with ASD and
      without intellectual disability and twenty-one typical male participants (TP)
      matched for age, intelligence quotient, handedness, race and parental
      socioeconomic status were recruited. Five EF domains were assessed and several
      DTI-based measurements of WMS [fractional anisotropy (FA), mean diffusivity (MD)
      and radial diffusivity (RD)] were estimated for eighteen white matter tracts. The
      ASD group had lower scores for attention (F = 8.37, p = 0.006) and response
      inhibition (F = 13.09, p = 0.001). Age-dependent changes of EF performance and
      WMS measurements were present in TP but attenuated in the ASD group. The
      strongest diagnosis-by-age effect was found for forceps minor, left anterior
      thalamic radiation and left cingulum angular bundle (all p's <= 0.002). In these
      tracts subjects with ASD tended to have equal or increased FA and/or reduced MD
      and/or RD at younger ages while controls had increased FA and/or reduced MD
      and/or RD thereafter. Only for TP individuals, increased FA in the left anterior
      thalamic radiation was associated with better response inhibition, while reduced
      RD in forceps minor and left cingulum angular bundle was related to better
      problem solving and working memory performance respectively. These findings
      provide novel insight into the age-dependency of EF performance and WMS in ASD,
      which can be instructive to cognitive training programs.

PMID- 28447270
TI  - Annual incidences of visual impairment during 10-year period in Mie prefecture,
      Japan.
AB  - PURPOSE: To determine the annual incidence of visual impairment in a Japanese
      population during a 10-year period. METHODS: We examined the physical disability
      certificates issued yearly between 2004 and 2013 in Mie prefecture, Japan. During
      this period 2468 visually impaired people were registered under the newly defined
      Act on Welfare of the Physically Disabled Persons' criteria. The age, sex
      distribution, and causes of visual impairment were determined from the
      certificates. RESULTS: The major causes of visual impairment during the ten-year
      period were glaucoma (23.3%), diabetic retinopathy (17.3%), retinitis pigmentosa
      (12.2%), macular degeneration (9.0%), chorioretinal degeneration or high myopia
      (7.4%), optic atrophy (5.8%), stroke or brain tumor (5.4%) and cataracts (3.7%).
      The incidence of glaucoma was significantly higher throughout the period (2004
      2013), and that of diabetic retinopathy was lower between 2007 and 2013. The
      incidence of retinitis pigmentosa did not change significantly during the 10-year
      period. The incidence of macular degeneration tended to increase between 2004 and
      2007, but it decreased significantly between 2007 and 2013. CONCLUSIONS: The
      results indicate that in Japan, the rates of the major causes of visual
      impairment altered in the most recent 10-year period reflecting the recent
      changes in the social background and advances in ocular and systemic treatment.

PMID- 28447272
TI  - A common trap of diagnostic tests : Disease prevalence and positive predictive
      value.

PMID- 28447271
TI  - The relationship between vascular endothelial dysfunction and treatment frequency
      in neovascular age-related macular degeneration.
AB  - PURPOSE: To assess the correlation between endothelial dysfunction and frequency
      of antivascular endothelial growth factor (anti-VEGF) treatment for neovascular
      age-related macular degeneration (nAMD). METHODS: We examined 64 consecutive
      patients with nAMD who were evaluated for endothelial function by use of
      peripheral arterial tonometry (EndoPAT 2000; Itamar Medical, Caesarea, Israel) at
      Toyama University Hospital from January 2015. We tallied the number of anti-VEGF
      treatments between January 2014 and December 2015 and determined the correlation
      between the number of anti-VEGF injections and endothelial function expressed as
      the reactive hyperemia index (RHI). Multiple regression analysis was also
      performed to identify the independent predictors of a larger number of
      injections. RESULTS: The mean number of anti-VEGF injections was 8.2 +/- 3.3. The
      mean lnRHI was 0.47 +/- 0.17. The lnRHI correlated with the number of anti-VEGF
      injections (r = -0.56; P = 0.030). The multiple regression analysis revealed that
      endothelial function, neovascular subtypes, and treatment regimens were
      associated with the number of injections. CONCLUSIONS: Endothelial dysfunction
      may affect the efficacy of anti-VEGF therapy. Neovascular subtypes may also
      predict a larger number of injections.

PMID- 28447273
TI  - Patients' Awareness, Usage and Impact of Hospital Report Cards in the US.
AB  - BACKGROUND: Little knowledge is available about the importance of hospital report
      cards in the US from the patients' perspective. It also remains unknown whether
      specific report cards with a stronger emphasis on clinical measures have a
      greater impact on hospital choice than general report cards that focus on online
      derived ratings. OBJECTIVE: The aim of this study was to determine the awareness
      and usage of hospital report cards as well as their impact on hospital choice in
      the US. METHODS: We conducted a cross-sectional study by surveying a stratified
      online sample (N = 1332) to ensure representativeness to the US online population
      (February 2015). RESULTS: Overall, 75% of all respondents (mean age 45.4 years;
      54% female) were aware of hospital report cards. Among these, 56% had used a
      report card to search for a hospital, and 80% of report card users stated having
      been influenced by a report card. Both the awareness and usage of general report
      cards were shown to be higher than for specific report cards. No significant
      differences could be detected regarding the impact between general or specific
      report cards on hospital choice. CONCLUSIONS: Our results indicate that hospital
      report cards play a considerable role among patients when searching for a
      hospital in the US; however, patients do not seem to have a preference regarding
      the type of report cards they use when selecting a hospital.

PMID- 28447274
TI  - Classification and regression tree model for predicting tracheostomy in patients
      with traumatic cervical spinal cord injury.
AB  - PURPOSE: In patients with cervical spinal cord injury (CSCI), respiratory
      compromise and the need for tracheostomy are common. The purpose of this study
      was to identify common risk factors for tracheostomy following traumatic CSCI and
      develop a decision tree for tracheostomy in traumatic CSCI patients without
      pulmonary function test. METHODS: Data of 105 trauma patients with CSCI admitted
      in our institution from April, 2008 to February, 2014 were retrospectively
      analyzed. Patients who underwent tracheostomy were compared to those who did not.
      Stepwise logistic regression analysis and classification and regression tree
      model were used to predict the risk factors for tracheostomy. RESULTS:
      Tracheostomy was performed in 20% of patients with traumatic CSCI on median
      hospital day 4. Patients who underwent tracheostomy tended to be more severely
      injured (higher Injury Severity Score, lower Glasgow Coma Score, and lower
      systolic blood pressure on admission) which required more frequent intubation in
      the emergency room (ER) with a higher rate of complete CSCI compared to those who
      did not. Upon multiple logistic analysis, Age >= 55 years (OR: 6.86, p = 0.037),
      Car accident (OR: 5.8, p = 0.049), injury above C5 (OR: 28.95, p = 0.009), ISS >=
      16 (OR: 12.6, p = 0.004), intubation in the ER (OR: 23.87, p = 0.001), and
      complete CSCI (OR: 62.14, p < 0.001) were significant predictors for the need of
      tracheostomy after CSCI. These factors can predict whether a new patient needs
      future tracheostomy with 91.4% accuracy. CONCLUSIONS: Age >= 55 years, injury
      above C5, ISS >= 16, Car accident, intubation in the ER, and complete CSCI were
      independently associated with tracheostomy after CSCI. CART analysis may provide
      an intuitive decision tree for tracheostomy.

PMID- 28447275
TI  - Risk Factors for Shoulder Dystocia: the Impact of Mother's Race and Ethnicity.
AB  - Shoulder dystocia is a rare but severe birth trauma where the neonate's shoulders
      fail to deliver after delivery of the head. Failure to deliver the shoulders
      quickly can lead to severe, long-term injury to the infant, including nerve
      injury, skeletal fractures, and potentially death. This observational study
      examined shoulder dystocia risk factors by race and ethnicity using a sample of
      19,236 pregnant women who presented for labor and delivery from July 1, 2010
      until June 30, 2013 at five locations. Multivariate analyses were used to
      identify risk factors associated with shoulder dystocia occurrence in
      racial/ethnic groups with high incidence rates. For White non-Hispanic mothers,
      the strongest risk factors were delivering past 40 weeks' gestation (odds ratio
      [OR] = 2.4; 95% confidence interval [CI] = 1.5, 3.9; p < .01) and use of epidural
      anesthesia during delivery (OR = 4.4; 95% CI = 3.0, 6.4; p < .01). Among Black
      non-Hispanic mothers, the risk factors with the greatest impact were use of
      epidural (OR = 5.3; 95% CI = 3.2, 8.7; p < .01) and having gestational diabetes
      and controlling the condition with insulin (OR = 4.6; 95% CI = 1.5, 13.8; p <
      .01). Additionally, among Hispanic mothers, having Spanish as primary language
      increased shoulder dystocia likelihood compared to those who did not cite it as
      their primary language (OR = 2.3; 95% CI = 1.1, 4.6; p < .05). This study
      provides evidence that risk factors for a labor and delivery condition can vary
      significantly across racial and ethnic subgroups. These differences emphasize the
      importance of evaluating risk by population subgroups and might provide a basis
      for labor and delivery clinicians to enhance personalized medicine to reduce
      adverse events.

PMID- 28447276
TI  - Increased dabigatran plasma concentration during Ibrutinib treatment: a case of
      cerebral hemorrhage and successful dabigatran reversal by idarucizumab.

PMID- 28447277
TI  - Assessment of PD-1 positive cells on initial and secondary resected tumor
      specimens of newly diagnosed glioblastoma and its implications on patient
      outcome.
AB  - Glioblastoma (GBM) is the most common type of malignant brain tumor and has a
      very poor prognosis. Most patients relapse within 12 months despite aggressive
      treatment and patient outcome after recurrent is extremely worse. This study was
      designed to clarify the change of the molecular expression, including programmed
      cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary
      resected tumor specimens and to address the influence of these expressions for
      patient outcome after second surgery of glioblastoma. We investigated 16
      patients, ranging in age from 14 to 65 years, with histologically verified WHO
      grade IV GBM, whose original tumor was resected between 2008 and 2014, and
      treated with fractionated radiotherapy and temozolomide. Four patients who were
      treated with immunotherapy using autologous formalin-fixed tumor vaccine were
      enrolled. All of the patients underwent secondary resection after tumor
      recurrence within 24 months. We carried out an immunohistochemical examination of
      the initial and secondary resected tumors from patients using a panel of immune
      system molecular markers, and assessed whether marker expression correlated with
      clinical outcomes. CD3, CD8 and PD-1 on tumor-infiltrating lymphocytes was
      significantly increased in secondary resected specimens compared with initially
      resected specimens (p <= 0.05). All patients expressed PD-L1 on tumor cells in
      initial and secondary resection specimens. Patients were divided into high or low
      expression group by median IHC score of PD-1 on initial or secondary resected
      specimens. No significant differences in patient outcomes were observed between
      high and low PD-1 or PD-L1 groups of initially resected specimens. In high
      expression group of secondary resected specimens, most patients score had
      increased which compared with initial resected tumor specimens. The PD-1 high
      expression score group of secondary resected specimens was associated with long
      progression-free survival and short survival after recurrence. PD-L1 expression
      was detected in almost all initial and secondary specimens. Patients with high PD
      1 expression of secondary specimen had bad prognosis after secondary resection.
      PD-1/PD-L1 pathway may be associated with patient outcome after second surgery of
      glioblastoma.

PMID- 28447279
TI  - Multi-modality molecular imaging of aortic aneurysms.
AB  - Aneurysms of the thoracic and abdominal aorta are common and can be associated
      with significant morbidity and mortality when complications, including
      dissection, rupture, or thrombosis, occur. Current approaches to diagnosis and
      risk stratification rely on measurements of aneurysm size and rate of growth,
      often using various imaging modalities, which may be suboptimal in identifying
      patients at the highest and lowest risk of complications. Targeting the
      biological processes underlying aneurysm formation and expansion with molecular
      imaging offers an exciting opportunity to characterize aortic aneurysms beyond
      size and address current gaps in our approach to diagnosis and treatment. In this
      review, we summarize the epidemiology and biology of aortic aneurysms and
      highlight the role of molecular imaging in furthering our understanding of
      aneurysm pathogenesis and its potential future role in guiding management.

PMID- 28447278
TI  - Invasiveness is associated with metastasis and decreased survival in
      hemangiopericytoma of the central nervous system.
AB  - Meningeal hemangiopericytoma (m-HPC) is a rare tumor of the central nervous
      system (CNS), which is distinguished clinically from meningioma by its tendency
      to recur and metastasize. The histological classification and grading scheme for
      m-HPC is still evolving and few studies have identified tumor features that are
      associated with metastasis. All patients at our institution with m-HPC were
      assessed for patient, tumor, and treatment characteristics associated with
      survival, recurrence, and metastasis. New findings were validated using the SEER
      database. Twenty-seven patients were identified in our institutional records with
      m-HPC with a median follow-up time of 85 months. Invasiveness was the strongest
      predictor of decreased overall survival (OS) and decreased metastasis-free
      survival (MFS) (p = 0.004 and 0.001). On subgroup analysis, bone invasion trended
      towards decreased OS (p = 0.056). Bone invasion and soft tissue invasion were
      significantly associated with decreased MFS (p = 0.001 and 0.012). An additional
      315 patients with m-HPC were identified in the SEER database that had information
      on tumor invasion and 263 with information on distant metastasis. Invasion was
      significantly associated with decreased survival (HR = 5.769, p = 0.007) and
      metastasis (OR 134, p = 0.000) in the SEER data. In this study, the authors
      identified a previously unreported tumor characteristic, invasiveness, as the
      strongest factor associated with decreased survival and metastasis. The
      association of invasion with decreased survival and metastasis was confirmed in a
      separate, larger, publicly available database. Invasion may be a useful parameter
      in the histological grading and clinical management of hemangiopericytoma of the
      CNS.

PMID- 28447280
TI  - Meta-analyses: How to critically appraise them?

PMID- 28447281
TI  - Assessment of left ventricular ejection fraction reserve in an era of decreasing
      frequency of myocardial ischemia during myocardial perfusion imaging.

PMID- 28447282
TI  - Guidelines in review: Comparison between AHA/ACC and ESC guidelines for the
      management of patients with ventricular arrhythmias and the prevention of sudden
      cardiac death.

PMID- 28447283
TI  - Adenosine stress myocardial perfusion imaging in octogenarians: Safety,
      tolerability, and long-term prognostic implications of hemodynamic response and
      SPECT-related variables.
AB  - BACKGROUND: Evaluation of tolerability, safety, and prognostic implications of
      adenosine stress myocardial perfusion imaging (MPI) in octogenarians. METHODS:
      370 octogenarians (49% known coronary artery disease) were studied. Hemodynamic
      response, MPI-related data, and rest-left ventricular ejection fraction (LVEF)
      based on echocardiography were registered per patient, and prospective follow-up
      was performed to document all-cause death (ACD), cardiac death (CD), myocardial
      infarction (MI), and late revascularization. RESULTS: No deaths or MIs were
      observed during adenosine infusion or the short-term post-infusion period. 86% of
      patients were able to tolerate a 6-minute infusion. All side effects terminated
      spontaneously after infusion cessation, except for one case of pulmonary oedema.
      After 9.3 years, there were 124 ACDs, 62 CDs, 16 MIs, and 35 revascularizations.
      Differences between survival curves of summed stress score (SSS)-based risk
      groups were significant for all end points (P < .001). SSS and LVEF were
      independent predictors of all end points (P <= .01) and lung uptake of cardiac
      end points. DeltaHR <10 bpm (OR = 1.78, P = .004) and inability to increase HR by
      >10 bpm and decrease systolic blood pressure by >10 mmHg (OR = 2, P = .02) during
      adenosine infusion were independent predictors of ACD and CD, respectively.
      Hemodynamic response variables, SSS, and lung uptake provided incremental
      prognostic value over pre-test data for ACD and CD. CONCLUSIONS: In
      octogenarians, adenosine stress MPI is well tolerated and provides effective long
      term risk stratification.

PMID- 28447284
TI  - Apical sparing pattern of left ventricular myocardial 99mTc-HMDP uptake in
      patients with transthyretin cardiac amyloidosis.
AB  - BACKGROUND: A decreased longitudinal strain in basal segments with a base-to-apex
      gradient has been described in patients with cardiac amyloidosis (CA).
      OBJECTIVES: Aim was to investigate the left ventricular (LV) regional
      distribution of early-phase 99mTc-Hydroxymethylene diphosphonate (99mTc-HMDP)
      uptake in patients with transthyretin-related cardiac amyloidosis (TTR-CA).
      METHODS: All patients underwent a whole-body planar 99mTc-HMDP scintigraphy
      acquired at 10-min post-injection (early-phase) followed by a thorax SPECT/CT.
      The segmental uptake (expressed as % of maximal myocardial HMDP uptake) was
      investigated on the AHA 17-segment model and 3-segment model (basal, mid-cavity,
      apical). RESULTS: Sixty-one TTR-CA patients were included of whom 29 were wild
      type (wt-TTR-CA) and 32 had hereditary TTR-CA (m-TTR-CA). Early myocardial 99mTc
      HMDP uptake occurred in all TTR-CA. In all patients, segmental analysis of the LV
      myocardial distribution of 99mTc-HMDP uptake showed an increased median uptake
      (interquartile range) in basal/mid-cavity segments compared to the lowest median
      uptake of apical segments (respectively, 79% [72%-86%] vs. 72% [64%-81%]; P < 10
      6). This pattern was similar in wt-TTR-CA group (78% [70%-84%] vs. 70% [61%-81%];
      P < 10-6), in m-TTR-CA group (80% [74%-86%] vs. 73 [66%-82%]; P < 10-7) and
      remained constant independently of the TTR mutation subtype with P ranging 10-5
      to 0.03. CONCLUSIONS: Early-phase myocardial scintigraphy identified regional
      distribution of 99mTc-HMDP uptake characterized by a base-to-apex gradient,
      corroborating echocardiographic, and cardiac magnetic resonance findings. This
      apical sparing pattern was similar across TTR-CA and TTR mutation subtypes.

PMID- 28447285
TI  - Hydrogen Sulfide and Ionic Liquids: Absorption, Separation, and Oxidation.
AB  - Economical and environmental concerns are the main motivations for development of
      energy-efficient processes and new eco-friendly materials for the capture of
      greenhouse gases. Currently, H2S capture is dominated by physical and/or chemical
      absorption technologies, which are, however, energy intensive and often
      problematic from an environmental point of view due to emission of volatile
      solvent components. Ionic liquids have been proposed as a promising alternative
      to conventional solvents because of their low volatility and other interesting
      properties. The aim of the present review paper is to provide a detailed overview
      of the achievements and difficulties that have been encountered in finding
      suitable ionic liquids for H2S capture. The effect of ionic liquid anions,
      cations, and functional groups on the H2S absorption, separation, and oxidation
      are highlighted. Recent developments on yet scarcely available molecular
      simulations and on the development of robust predictive methods are also
      discussed.

PMID- 28447286
TI  - The body as constitutive element phenomenology and psychoanalysis on our view of
      ourselves and others.
AB  - The aim of this manuscript is to highlight that from the phenomenology and
      psychoanalysis point of view, the meaning of the notion of the body is different
      from the medical biologicist discourse. In psychoanalysis, the body is an
      erogenized body. It is constituted as an object for another self. Similarly, in
      phenomenology, the body is an own body in first instance. It is the body of a
      self, rather than a living body and a material body. Both positions enable us to
      understand how this conceptualization of the body is essential in any human
      field. Especially in the clinic, the position of the subject before the other
      will lead to a specific form of intervention. From this understanding of the
      human body, both phenomenology and psychoanalysis confirm that the biologicist
      understanding of the body, presumed by all psychological and medical practices,
      is insufficient.

PMID- 28447287
TI  - Topography and correlation of radial peripapillary capillary density network with
      retinal nerve fibre layer thickness.
AB  - PURPOSE: To analyse the expansion of radial peripapillary capillary (RPC) network
      with optical coherence tomography angiography (OCT-A) in normal human eyes and
      correlate RPC density with retinal nerve fibre layer thickness (RNFLT) at various
      distances from the optic nerve head (ONH) edge. METHODS: Fifty eyes of 50 healthy
      subjects underwent imaging with RTVue XR-100 Avanti OCT. OCT-A scans of Angio
      disc (6 * 6 mm) and Angio retina (8 * 8 mm) were combined to create a wide-field
      montage image of the RPC network. RPC density and RNFLT was calculated at
      different circle diameter around the ONH, and their correlation was measured.
      RESULTS: In the arcuate region, RPC was detected as far as 8.5 mm from the ONH
      edge, but not around the perifoveal area within 0.025 +/- 0.01 mm2. The mean RPC
      density (0.1556 +/- 0.015) and RNFLT (245.96 +/- 5.79) were highest at 1.5 mm
      from ONH margin, and there was a trend in its decline, in a distance-dependent
      manner, with the least density at 8.5 mm (all P < 0.0001). Highest RPC density
      was noted in the arcuate fibre region at all the distances. Overall mean RPC
      density correlated significantly (P < 0.0001) with the overall mean RNFLT.
      CONCLUSIONS: Wide-field montage OCT-A angiograms can visualize expansion of the
      RPC network, which is useful in obtaining information about various retinal
      disorders. The results obtained support the hypothesis that the RPC network could
      be responsible for RNFL nourishment.

PMID- 28447288
TI  - Understanding the Relationship Between Subjective Wellbeing and Gambling
      Behavior.
AB  - This paper examines the relationship between gambling behavior and subjective
      wellbeing. It is often asserted that populations consist of different types of
      gamblers: those for whom gambling is a harmless leisure activity and those
      (pathological/problem gamblers) for whom the activity has harmful effects. One
      might, therefore, assume that subjective wellbeing will be negativity associated
      with an individual's level of gambling addiction. Alternatively, gamblers may
      choose to gamble because they derive utility from participating in this activity
      and so the relationship between happiness and gambling might be positively
      correlated. In this paper we test this association, empirically, using data from
      the 2010 British Gambling Prevalence Survey. The statistically significant
      findings from this analysis support the hypothesis that individual wellbeing
      falls as gambling disorder increases.

PMID- 28447289
TI  - Electroencephalographic Evidence of Abnormal Anticipatory Uncertainty Processing
      in Gambling Disorder Patients.
AB  - Putting money at stake produces anticipatory uncertainty, a process that has been
      linked to key features of gambling. Here we examined how learning and individual
      differences modulate the stimulus preceding negativity (SPN, an
      electroencephalographic signature of perceived uncertainty of valued outcomes) in
      gambling disorder patients (GDPs) and healthy controls (HCs), during a non
      gambling contingency learning task. Twenty-four GDPs and 26 HCs performed a
      causal learning task under conditions of high and medium uncertainty (HU, MU;
      null and positive cue-outcome contingency, respectively). Participants were asked
      to predict the outcome trial-by-trial, and to regularly judge the strength of the
      cue-outcome contingency. A pre-outcome SPN was extracted from simultaneous
      electroencephalographic recordings for each participant, uncertainty level, and
      task block. The two groups similarly learnt to predict the occurrence of the
      outcome in the presence/absence of the cue. In HCs, SPN amplitude decreased as
      the outcome became predictable in the MU condition, a decrement that was absent
      in the HU condition, where the outcome remained unpredictable during the task.
      Most importantly, GDPs' SPN remained high and insensitive to task type and block.
      In GDPs, the SPN amplitude was linked to gambling preferences. When both groups
      were considered together, SPN amplitude was also related to impulsivity. GDPs
      thus showed an abnormal electrophysiological response to outcome uncertainty, not
      attributable to faulty contingency learning. Differences with controls were
      larger in frequent players of passive games, and smaller in players of more
      active games. Potential psychological mechanisms underlying this set of effects
      are discussed.

PMID- 28447291
TI  - Investigation of contact characteristics and frictional properties of natural
      articular cartilage at two different surface configurations.
AB  - Natural cartilage surfaces were macroscopically curved with multi-porous
      viscoelastic biologic materials with extremely high water, but whether curved
      surface configuration could play an important role on the contact and frictional
      properties of natural cartilages fails to be completely understood up to now. In
      this current study, cartilage samples came from the 18-24 month-old bovine
      femora. Contact characteristic and frictional properties at two cartilage
      configurations were investigated using the UMT-2 testing rig and the five-point
      sliding average method would be adopted to analyze these tested data. These
      results indicated the surface displacement was extremely associated with the
      plate cartilage surface and seemed to be a representative of cartilage surface
      configuration. The summit of the surface load lagged behind that of the surface
      displacement at the same condition. Coefficient of friction showed obviously
      different variation with time at two cartilage surface configurations due to the
      fact that these two surface displacements had different amplitudes and opposite
      directions as a function of the sliding length. Therefore, surface configuration
      played the main role on these variables of contact displacement, contact load and
      coefficient of friction due to the direction and magnitude of the surface
      displacement while applied load and sliding velocity had a secondary role.
      Natural cartilage surfaces were macroscopically curved with multi-porous
      viscoelastic biologic materials with extremely high water, but whether curved
      surface configuration could play an important role on the contact and frictional
      properties of natural cartilages fails to be completely understood up to now. In
      this study, two different cartilage configurations were adopted to investigate
      natural cartilage properties, and the five-point sliding average method would be
      used to analyze these tested data. These results indicated the contact
      displacement was consisted of cartilage deformation and surface displacement
      while contact load was composed of steady load and surface load (as shown in the
      figure, panels (a) and (b)). Surface displacement was greatly associated with the
      plate cartilage surface and seemed to be a representative of cartilage surface
      configuration. These two surface displacements had different amplitudes and
      opposite directions as a function of the sliding length (as shown in panel (c)).
      The summit of the surface load lagged behind that of the surface displacement at
      the same condition (as shown in panel (d)). Surface displacement and surface load
      in the contact characteristic of natural cartilages were extremely related with
      the cartilage configurations. and their correlation coefficients varied
      periodically with the moving time (as shown in panel (e)). Coefficient of
      friction showed obviously different variation with time (as shown in panel (f)).
      Therefore, surface configuration played the main role on these variables of
      contact displacement, contact load and coefficient of friction due to the
      direction and magnitude of the surface displacement while applied load and
      sliding velocity had a secondary role. Variation in contact and frictional
      properties of natural cartilage at two different surface configurations (a)
      Contact displacement and its parts varied with time; (b) Contact load and its
      parts varied with time;

PMID- 28447290
TI  - Regulation of Cardiomyocyte T-Tubular Structure: Opportunities for Therapy.
AB  - PURPOSE OF REVIEW: Membrane invaginations called t-tubules play an integral role
      in triggering cardiomyocyte contraction, and their disruption during diseases
      such as heart failure critically impairs cardiac performance. In this review, we
      outline the growing understanding of the malleability of t-tubule structure and
      function, and highlight emerging t-tubule regulators which may be exploited for
      novel therapies. RECENT FINDINGS: New technologies are revealing the nanometer
      scale organization of t-tubules, and their functional junctions with the
      sarcoplasmic reticulum called dyads, which generate Ca2+ sparks. Recent data have
      indicated that the dyadic anchoring protein junctophilin-2, and the membrane
      bending protein BIN1 are key regulators of dyadic formation and maintenance.
      While the underlying signals which control expression and localization of these
      proteins remain unclear, accumulating data support an important role of
      myocardial workload. Although t-tubule alterations are believed to be a key cause
      of heart failure, the plasticity of these structures also creates an opportunity
      for therapy. Promising recent data suggest that such therapies may specifically
      target junctophilin-2, BIN1, and/or mechanotransduction.

PMID- 28447292
TI  - Ecology of the Human Opportunistic Black Yeast Exophiala dermatitidis Indicates
      Preference for Human-Made Habitats.
AB  - Exophiala dermatitidis is an ascomycetous black yeast from the order
      Chaetothyriales. Its growth characteristics include the polymorphic life cycle,
      ability to grow at high and low temperatures, at a wide pH range, survival at
      high concentrations of NaCl, and survival at high UV and radioactive radiation.
      Exophiala dermatitidis causes deep or localized phaeohyphomycosis in immuno
      compromised people worldwide and is regularly encountered in the lungs of cystic
      fibrosis patients. Regardless of numerous ecological studies worldwide, little is
      known about its natural habitat or the possible infection routes. The present
      review summarizes the published data on its frequency of occurrence in nature and
      in man-made habitats. We additionally confirmed its presence with culture
      depending methods from a variety of habitats, such as glacial meltwater, mineral
      water, mineral-rich salt-pan mud, dishwashers, kitchens and different
      environments polluted with aromatic hydrocarbons. In conclusion, the frequency of
      its recovery was the highest in man-made indoor habitats, connected to water
      sources, and exposed to occasional high temperatures and oxidative stress.

PMID- 28447293
TI  - Shielding of the geomagnetic field reduces hydrogen peroxide production in human
      neuroblastoma cell and inhibits the activity of CuZn superoxide dismutase.
AB  - Accumulative evidence has shown the adverse effects of a geomagnetic field
      shielded condition, so called a hypomagnetic field (HMF), on the metabolic
      processes and oxidative stress in animals and cells. However, the underlying
      mechanism remains unclear. In this study, we evaluate the role of HMF on the
      regulation of cellular reactive oxygen species (ROS) in human neuroblastoma SH
      SY5Y cells. We found that HMF exposure led to ROS decrease, and that restoring
      the decrease by additional H2O2 rescued the HMF-enhanced cell proliferation. The
      measurements on ROS related indexes, including total anti-oxidant capacity, H2O2
      and superoxide anion levels, and superoxide dismutase (SOD) activity and
      expression, indicated that the HMF reduced H2O2 production and inhibited the
      activity of CuZn-SOD. Moreover, the HMF accelerated the denaturation of CuZn-SOD
      as well as enhanced aggregation of CuZn-SOD protein, in vitro. Our findings
      indicate that CuZn-SOD is able to response to the HMF stress and suggest it a
      mediator of the HMF effect.

PMID- 28447294
TI  - The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71
      infection.
AB  - Entero virus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and
      occasionally leads to severe neurological complications and even death. Scavenger
      receptor class B member 2 (SCARB2) is a functional receptor for EV71, that
      mediates viral attachment, internalization, and uncoating. However, the exact
      binding site of EV71 on SCARB2 is unknown. In this study, we generated a
      monoclonal antibody (mAb) that binds to human but not mouse SCARB2. It is named
      JL2, and it can effectively inhibit EV71 infection of target cells. Using a set
      of chimeras of human and mouse SCARB2, we identified that the region containing
      residues 77-113 of human SCARB2 contributes significantly to JL2 binding. The
      structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region
      of SCARB2 involving alpha-helices 2, 5, and 14. Our results provide new insights
      into the potential binding sites for EV71 on SCARB2 and the molecular mechanism
      of EV71 entry.

PMID- 28447296
TI  - Addressing the Needs of Children and Youth in the Context of War and Terrorism:
      the Technological Frontier.
AB  - This paper reviews recent literature on the mental health needs of youth in the
      context of war and terrorism. A human rights lens is used to explore issues of
      accessibility and sustainability in service utilization during times of crisis.
      The authors present the evolution of services over the last several decades,
      progressing through individual, school-based, and community-wide interventions by
      exploring models that focus on symptom reduction and building resilience. This
      paper highlights the benefits and limitations of traditional intervention methods
      and proposes a new frontier of intervention development and research. The authors
      focus on the emerging field of e-mental health services and specifically
      highlight the utility of virtual reality games in treating trauma-exposed youth.
      The rapid and easily accessible nature of e-mental health models is presented as
      one potential solution to barriers in accessibility that can help promote the
      human rights of youth exposed to war and terrorism.

PMID- 28447295
TI  - Functional Expression of P-glycoprotein and Organic Anion Transporting
      Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for
      Improved CNS Drug Delivery?
AB  - Drug delivery to the central nervous system (CNS) is greatly limited by the blood
      brain barrier (BBB). Physical and biochemical properties of the BBB have rendered
      treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R)
      component, extremely difficult. Targeting endogenous BBB transporters from the
      ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the
      solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs
      in humans; Oatps in rodents)) has been suggested as a strategy that can improve
      delivery of drugs to the brain. With respect to P-gp, direct pharmacological
      inhibition using small molecules or selective regulation by targeting
      intracellular signaling pathways has been explored. These approaches have been
      largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics.
      Therefore, our laboratory has proposed that optimization of CNS drug delivery,
      particularly for treatment of diseases with an H/R component, can be achieved by
      targeting Oatp isoforms at the BBB. As the major drug transporting Oatp isoform,
      Oatp1a4 has demonstrated blood-to-brain transport of substrate drugs with
      neuroprotective properties. Furthermore, our laboratory has shown that targeting
      Oatp1a4 regulation (i.e., TGF-beta signaling mediated via the ALK-1 and ALK-5
      transmembrane receptors) represents an opportunity to control Oatp1a4 functional
      expression for the purpose of delivering therapeutics to the CNS. In this review,
      we will discuss limitations of targeting P-gp-mediated transport activity and the
      advantages of targeting Oatp-mediated transport. Through this discussion, we will
      also provide critical information on novel approaches to improve CNS drug
      delivery by targeting endogenous uptake transporters expressed at the BBB.

PMID- 28447297
TI  - Generating Neuron Geometries for Detailed Three-Dimensional Simulations Using
      AnaMorph.
AB  - Generating realistic and complex computational domains for numerical simulations
      is often a challenging task. In neuroscientific research, more and more one
      dimensional morphology data is becoming publicly available through databases.
      This data, however, only contains point and diameter information not suitable for
      detailed three-dimensional simulations. In this paper, we present a novel
      framework, AnaMorph, that automatically generates water-tight surface meshes from
      one-dimensional point-diameter files. These surface triangulations can be used to
      simulate the electrical and biochemical behavior of the underlying cell. In
      addition to morphology generation, AnaMorph also performs quality control of the
      semi-automatically reconstructed cells coming from anatomical reconstructions.
      This toolset allows an extension from the classical dimension-reduced modeling
      and simulation of cellular processes to a full three-dimensional and morphology
      including method, leading to novel structure-function interplay studies in the
      medical field. The developed numerical methods can further be employed in other
      areas where complex geometries are an essential component of numerical
      simulations.

PMID- 28447298
TI  - A new species of Tinrovia Mamaev, 1987 (Monogenea: Microcotylidae) from the deep
      sea fish Notacanthus bonaparte Risso (Notacanthiformes: Notacanthidae) in the
      Western Mediterranean and the North East Atlantic.
AB  - A new microcotylid, Tinrovia mamaevi n. sp. (Monogenea: Polyopisthocotylea), is
      described from the gills of Notacanthus bonaparte Risso (Notacanthiformes:
      Notacanthidae), sampled in the Western Mediterranean and North East Atlantic.
      This species is allocated to the subfamily Syncoelicotylinae Mamaev & Zubchenko,
      1978 due to the possession of a symmetrical haptor with two separate frills. The
      clamps in T. mamaevi n. sp. are of the "microcotylid" type, arranged in two
      distinct lateral haptoral frills; the genital atrium and the copulatory organ are
      armed and the vaginal pore is unarmed. The new species differs from the type- and
      only species of the genus, T. papiliocauda Mamaev, 1987, in having a shorter and
      narrower haptor with a smaller number of clamps. Clamps are also smaller in the
      new species, testes are more numerous, the genital atrium is smaller, divided
      into two lateral lobes (instead of five) with a smaller number of spines and the
      eggs have a short and a long filament (instead of two short filaments). The host
      species and locality of T. mamaevi n. sp. also differ as T. papiliocauda which
      was recorded in Notacanthus sexspinis Richardson from the South Pacific.

PMID- 28447299
TI  - Vancomycin-loaded HPMC microparticles embedded within injectable thermosensitive
      chitosan hydrogels.
AB  - Antibiotic use is an essential method for the treatment of bacterial infections.
      In certain cases, antibiotics are not effective because of the distribution
      problems caused by physiological barriers in the body. Such problems are thought
      to be minimized by development of sustained release systems which involve
      implantation of antibiotic loaded polymeric systems directly to the site of
      infection. In this work, a new composite vancomycin hydrochloride release system
      based on HPMC microparticles and chitosan/glycerophosphate (Ch/Gp)
      thermosensitive hydrogel was designed for the aim of local treatment of
      osteomyelitis. Vancomycin-loaded HPMC microparticles (Van-HPMCs) were prepared by
      spray drying method. The SEM results showed that these particles had a mean
      diameter of 1.5-6.4 MUm with a narrow size distribution and homogeneous particle
      production. Their drug encapsulation efficiency was 72.6%. The Van-HPMCs were
      embedded in an injectable Ch/Gp solution to introduce a composite drug release
      platform (Van/HPMC-Ch/Gp). In vitro release studies indicated that inclusion of
      the Van-HPMCs into the Ch/Gp hydrogel caused a reduction in both the release rate
      and total amount of vancomycin release, which suggests that HPMC microparticles
      entrapped into the Ch/Gp hydrogels showed more suitable sustained release
      kinetics for local antibiotics delivery.

PMID- 28447300
TI  - Erratum to: Emergence Delirium in Pediatric Anesthesia.

PMID- 28447301
TI  - Management of Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant
      deterioration in quality of life and is perceived by patients as a major adverse
      effect of the treatment. This review summarizes the safety and efficacy of
      current antiemetic agents for the prevention of CINV in children. Information on
      antiemetic prophylaxis for CINV in children was obtained from a literature review
      of current peer-reviewed articles and recent international guidelines. The
      literature review and the international antiemetic guidelines provide
      recommendations for use of specific antiemetics in children based on the
      emetogenicity of the chemotherapy. 5-Hydroxytryptamine-3 (5-HT3) receptor
      antagonists have been safe and effective in the prevention of acute emesis with a
      few patients experiencing mild headache. No adequate studies have been conducted
      to date for specific recommendations for the prevention of delayed nausea and
      vomiting in children. The neurokinin (NK)-1 receptor antagonist aprepitant has
      been approved by the US FDA for use in children of a specific age and weight. No
      studies for the NK1 receptor antagonists netupitant and rolapitant in children
      have been conducted. Olanzapine, an antipsychotic, has been shown to be safe and
      effective in preventing nausea and emesis in adult patients receiving
      chemotherapy. Its use in children has been limited to children with poor control
      of CINV; more studies are necessary in this population. In conclusion,
      practitioners should follow international antiemetic guidelines to provide
      patients with the specific antiemetics in the recommended dose for the highest
      possible quality of care.

PMID- 28447302
TI  - Comment on the New Indian Injection Technique Recommendations: Critical Appraisal
      of the Real-World Implementation of the Current Guidelines.
AB  - With an eye on the sequence of two Indian papers concurrently published in
      Diabetes Therapy, this paper analyzes skin differences among races and points to
      a lack of organized structured education sessions as the main cause of the high
      prevalence of lipodystrophy (LD) and consequent poor metabolic control. Only half
      of all insulin-treated patients reach their therapeutic targets worldwide. The
      factors involved in this are manifold, including the choice of overlong and
      repeatedly reused needles, as well as a failure to systematically rotate
      injection sites, all of which lead to skin LD. Regularly issued guidelines and
      expert recommendations provide suggestions about how to correct poor injection
      techniques, but LD still occurs at a high rate and is associated with poor
      metabolic control, a high risk of complications, frequent severe hypoglycemic
      episodes, and huge health and social costs. Poor knowledge of subcutaneous tissue
      anatomy and the physiological response to insulin injection by both health care
      personnel and patients may contribute to this problem. Moreover, differences in
      body structure among the races present in our multiethnic societies must be taken
      into account when choosing needle length and shooting technique in order to avoid
      accidental intramuscular injections.

PMID- 28447303
TI  - Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with
      Autism Spectrum Disorder.
AB  - Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming
      increasingly common, placing individuals at risk for antipsychotic-induced weight
      gain and associated complications. Metformin hydrochloride, a biguanide
      medication FDA-approved for treatment of type-2 diabetes in youth, may hold
      promise for treatment of antipsychotic-induced weight gain in youth with ASD. In
      this report we assess the long-term impact of metformin on antipsychotic
      associated weight gain in a naturalistic sample of 53 youth with ASD. Results
      indicate that treatment with metformin stabilized BMI z-score over a nearly 2
      year mean treatment period. Further work is indicated to determine the safety and
      efficacy of metformin treatment in youth with ASD, as well as predictors of
      response as a treatment for antipsychotic-induced weight gain.

PMID- 28447305
TI  - A Discrepancy in Comprehension and Production in Early Language Development in
      ASD: Is it Clinically Relevant?
AB  - This study examined the extent to which a discrepant comprehension-production
      profile (i.e., relatively more delayed comprehension than production) is
      characteristic of the early language phenotype in autism spectrum disorders (ASD)
      and tracked the developmental progression of the profile. Our findings indicated
      that a discrepant comprehension-production profile distinguished toddlers (30
      months) with ASD from late talkers without ASD (91% sensitivity, 100%
      specificity) in groups that were comparable on expressive language, age, and
      socioeconomic status. Longitudinal data for children with ASD revealed that the
      discrepant profile steadily decreased from 30 to 44 months until there was no
      significant comprehension-production difference at 66 months. In conclusion,
      results suggest that lower comprehension than production may be an age-specific
      marker of toddlers with ASD.

PMID- 28447304
TI  - Self-Report and Brain Indicators of Impaired Emotion Regulation in the Broad
      Autism Spectrum.
AB  - Although not used as a diagnostic criterion, impaired emotion regulation is
      frequently observed in autism. The present study examined self-reported use of
      emotion regulation strategies in individuals scoring low or high on autistic
      traits. In addition, the late positive potential, which is sensitive to emotional
      arousal, was used to examine the effect of one strategy, reappraisal. Reporting
      more autistic traits was related to using more maladaptive and fewer adaptive
      emotion regulation strategies. Across both groups, no attenuation of the late
      positive potential during downregulation of unpleasant pictures was found,
      possibly because of the used valence-changing reappraisal operationalisation.
      Hence, although self-report indicated impaired emotion regulation in individuals
      high on autistic traits, electrophysiological findings could not confirm this.

PMID- 28447306
TI  - The Effects of Early Language on Age at Diagnosis and Functioning at School Age
      in Children with Autism Spectrum Disorder.
AB  - Research suggests that toddlers with no language delay (NLD) should have better
      outcomes than those with language delay (LD). However, the predictive utility of
      language milestones relative to co-varying factors such as age at diagnosis, IQ,
      and ASD symptomatology is unclear. This study compared school-aged children with
      ASD and NLD (n = 59) to a well-matched group with ASD and LD (n = 59). The LD
      group was diagnosed at younger ages and their historical ASD symptoms were more
      severe than the NLD group. The groups were similar in current ASD symptoms and
      adaptive functioning at school age. Language milestones were correlated with
      adaptive functioning, but IQ and social symptoms of ASD were stronger predictors
      of functioning at school age. Therefore, language milestones may not be the best
      indicators of prognosis for children who are diagnosed after toddlerhood.

PMID- 28447307
TI  - Erratum to: Editorial: 2016 in Review.

PMID- 28447309
TI  - Markov Decision Process Measurement Model.
AB  - Within-task actions can provide additional information on student competencies
      but are challenging to model. This paper explores the potential of using a
      cognitive model for decision making, the Markov decision process, to provide a
      mapping between within-task actions and latent traits of interest. Psychometric
      properties of the model are explored, and simulation studies report on parameter
      recovery within the context of a simple strategy game. The model is then applied
      to empirical data from an educational game. Estimates from the model are found to
      correlate more strongly with posttest results than a partial-credit IRT model
      based on outcome data alone.

PMID- 28447308
TI  - Determinants of stage at diagnosis of breast cancer in Nigerian women:
      sociodemographic, breast cancer awareness, health care access and clinical
      factors.
AB  - PURPOSE: Advanced stage at diagnosis is a common feature of breast cancer in Sub
      Saharan Africa (SSA), contributing to poor survival rates. Understanding its
      determinants is key to preventing deaths from this cancer in SSA. METHODS: Within
      the Nigerian Integrative Epidemiology of Breast Cancer Study, a multicentred case
      control study on breast cancer, we studied factors affecting stage at diagnosis
      of cases, i.e. women diagnosed with histologically confirmed invasive breast
      cancer between January 2014 and July 2016 at six secondary and tertiary hospitals
      in Nigeria. Stage was assessed using clinical and imaging methods. Ordinal
      logistic regression was used to examine associations of sociodemographic, breast
      cancer awareness, health care access and clinical factors with odds of later
      stage (I, II, III or IV) at diagnosis. RESULTS: A total of 316 women were
      included, with a mean age (SD) of 45.4 (11.4) years. Of these, 94.9% had stage
      information: 5 (1.7%), 92 (30.7%), 157 (52.4%) and 46 (15.3%) were diagnosed at
      stages I, II, III and IV, respectively. In multivariate analyses, lower
      educational level (odds ratio (OR) 2.35, 95% confidence interval: 1.04, 5.29),
      not believing in a cure for breast cancer (1.81: 1.09, 3.01), and living in a
      rural area (2.18: 1.05, 4.51) were strongly associated with later stage, whilst
      age at diagnosis, tumour grade and oestrogen receptor status were not. Being
      Muslim (vs. Christian) was associated with lower odds of later stage disease
      (0.46: 0.22, 0.94). CONCLUSION: Our findings suggest that factors that are
      amenable to intervention concerning breast cancer awareness and health care
      access, rather than intrinsic tumour characteristics, are the strongest
      determinants of stage at diagnosis in Nigerian women.

PMID- 28447310
TI  - Asymptotics of AIC, BIC, and RMSEA for Model Selection in Structural Equation
      Modeling.
AB  - Model selection is a popular strategy in structural equation modeling (SEM). To
      select an "optimal" model, many selection criteria have been proposed. In this
      study, we derive the asymptotics of several popular selection procedures in SEM,
      including AIC, BIC, the RMSEA, and a two-stage rule for the RMSEA (RMSEA-2S). All
      of the results are derived under weak distributional assumptions and can be
      applied to a wide class of discrepancy functions. The results show that both AIC
      and BIC asymptotically select a model with the smallest population minimum
      discrepancy function (MDF) value regardless of nested or non-nested selection,
      but only BIC could consistently choose the most parsimonious one under nested
      model selection. When there are many non-nested models attaining the smallest MDF
      value, the consistency of BIC for the most parsimonious one fails. On the other
      hand, the RMSEA asymptotically selects a model that attains the smallest
      population RMSEA value, and the RESEA-2S chooses the most parsimonious model from
      all models with the population RMSEA smaller than the pre-specified cutoff. The
      empirical behavior of the considered criteria is also illustrated via four
      numerical examples.

PMID- 28447311
TI  - Attenuation of Glutamate-Induced Excitotoxicity by Withanolide-A in Neuron-Like
      Cells: Role for PI3K/Akt/MAPK Signaling Pathway.
AB  - Glutamate-induced excitotoxicity is one of the major underlying mechanisms for
      neurodegenerative diseases. Efforts are being made to treat such conditions with
      an array of natural compounds that can modulate the release of glutamate or the
      underlying mechanisms associated with it. Withania somnifera extract has potent
      pharmacologic activity similar to that of Korean Ginseng tea and is used to treat
      several neuronal disorders. However, to date, little efforts have been made to
      evaluate individual constituents of this plant for neurodegenerative disorders.
      Present study was carried out to investigate withanolide-A, one of the active
      constituents of Withania somnifera against glutamate-induced excitotoxicity in
      retinoic acid differentiated Neuro2a neuroblastoma cells. The results indicated
      that glutamate treatment for 2 h induced death in cells that was significantly
      attenuated by pre-treatment with MK-801 (specific NMDA receptor antagonist) and
      different concentrations of withanolide-A. Withanolide-A abated the glutamate
      induced influx of intracellular calcium and excessive ROS production
      significantly. Further on, glutamate treatment resulted in increased levels of
      pro-apoptotic and decreased levels of anti-apoptotic proteins, and these protein
      levels were normalized by various doses of withanolide-A. All of these protective
      effects were partly due to inhibition of MAPK family proteins and activation of
      PI3K/Akt signaling. Thus, our results suggest that withanolide-A may serve as
      potential neuroprotective agent.

PMID- 28447312
TI  - Bone Quality in Chronic Kidney Disease: Definitions and Diagnostics.
AB  - PURPOSE OF REVIEW: In this paper, we review the epidemiology, diagnosis, and
      pathogenesis of fractures and renal osteodystrophy. RECENT FINDINGS: The role of
      bone quality in the pathogenesis of fracture susceptibility in chronic kidney
      disease (CKD) is beginning to be elucidated. Bone quality refers to bone material
      properties, such as cortical and trabecular microarchitecture, mineralization,
      turnover, microdamage, and collagen content and structure. Recent data has added
      to our understanding of the effects of CKD on alterations to bone quality,
      emerging data on the role of abnormal collagen structure on bone strength, the
      potential of non-invasive methods to inform our knowledge of bone quality, and
      how we can use these methods to inform strategies that protect against bone loss
      and fractures. However, more prospective data is required. CKD is associated with
      abnormal bone quality and strength which results in high fracture incidence.

PMID- 28447313
TI  - Stereotactic ablative radiation therapy for brain metastases with volumetric
      modulated arc therapy and flattening filter free delivery: feasibility and early
      clinical results.
AB  - AIM: For selected patients with brain metastases (BMs), the role of stereotactic
      radiosurgery (SRS) or fractionated stereotactic radiotherapy (SFRT) is well
      recognized. The recent introduction of flattening filter free (FFF) delivery
      during linac-based SRS or SFRT allows shorter beam-on-time, improving patients'
      comfort and facility workflow. Nevertheless, limited experiences evaluated the
      impact of FFF linac-based SRS and SFRT in BMs treatment. Aim of the current study
      was to analyze SRS/SFRT linac-based FFF delivery for BMs in terms of dosimetric
      and early clinical results. MATERIALS AND METHODS: Patients with life expectancy
      >3 months, number of BMs <5, diameter <3 cm, and controlled or synchronous
      primary tumor received SRS/SFRT. The prescribed total dose and fractionation,
      based on BMs size and proximity to organs at risk, ranged from 15 Gy in 1
      fraction to 30 Gy in 5 fractions. A FFF volumetric modulated arc therapy (VMAT)
      plan was generated with one or two coplanar partial arcs. Toxicity was assessed
      according to CTCAE v4.0. RESULTS: From April 2014 to February 2016, 45 patients
      (89 BMs) were treated with SRS/SFRT linac-based FFF delivery. The mean beam-on
      time was 140 s for each lesion (range 90-290 s) and the average brain Dmean was 1
      Gy (range 0.1-4.8 Gy). At the time of analysis, local control was reported in
      93.2% (83/89 BMs). With a median follow-up time of 12 months (range 1-27 months),
      the median overall survival was 14 months and the 6-month overall survival was
      77%. Finally, the median intracranial disease control was 11 months. Acute and
      late toxicities were acceptable without severe events (no adverse events >=G2
      were recorded). CONCLUSIONS: These preliminary results highlighted the
      feasibility and safety of linac-based SRS/SFRT with FFF mode for BMs patients. A
      longer follow-up is necessary to confirm the efficacy of this treatment modality
      in BM patients.

PMID- 28447314
TI  - Inhibition of the insulin-like growth factor-1 receptor potentiates acute effects
      of castration in a rat model for prostate cancer growth in bone.
AB  - Prostate cancer (PCa) patients with bone metastases are primarily treated with
      androgen deprivation therapy (ADT). Less pronounced ADT effects are seen in
      metastases than in primary tumors. To test if acute effects of ADT was enhanced
      by concurrent inhibition of pro-survival insulin-like growth factor 1 (IGF-1),
      rats were inoculated with Dunning R3327-G tumor cells into the tibial bone marrow
      cavity and established tumors were treated with castration in combination with
      IGF-1 receptor (IGF-1R) inhibitor NVP-AEW541, or by each treatment alone. Dunning
      R3327-G cells were stimulated by androgens and IGF-1 in vitro. In rat tibia,
      Dunning R3327-G cells induced bone remodeling, identified through increased
      immunoreactivity of osteoblast and osteoclast markers. Tumor cells occasionally
      grew outside the tibia, and proliferation and apoptotic rates a few days after
      treatment were evaluated by scoring BrdU- and caspase-3-positive tumor cells
      inside and outside the bone marrow cavity, separately. Apoptosis was
      significantly induced outside, but unaffected inside, the tibial bone by either
      castration or NVP-AEW541, and the maximum increase (2.7-fold) was obtained by the
      combined treatment. Proliferation was significantly reduced by NVP-AEW541,
      independently of growth site, although the maximum decrease (24%) was observed
      when NVP-AEW541 was combined with castration. Tumor cell IGF-1R immunoreactivity
      was evaluated in clinical PCa bone metastases (n = 61), and positive staining was
      observed in most cases (74%). In conclusion, IGF-1R inhibition may be evaluated
      in combination with ADT in patients with metastatic PCa, or in combination with
      therapies for the subsequent development of castration-resistant disease,
      although diverse responses could be anticipated depending on metastasis site.

PMID- 28447315
TI  - Neglected hip dislocation: an unusual presentation, its management and review of
      the literature.
AB  - Neglected traumatic posterior hip dislocation is not an uncommon condition seen
      in developing countries. Its treatment is fraught with great difficulties and
      controversies. Here we present a 31-year-old female patient presented to our
      hospital 2 years after sustaining an accident. She had gone through multiple
      treatments for her dislocated hip without any success. After arrival to our
      hospital, patient managed by constrained total hip replacement (THR). Her Harris
      hip score improved from 48 (preoperative) to 81 (postoperative). On follow-up she
      had a good range of movement of the hip with no pain, deformity and limb length
      discrepancy. Constrained THR provides promising results in neglected hip
      dislocation.

PMID- 28447316
TI  - Mining and Environmental Health Disparities in Native American Communities.
AB  - PURPOSE OF REVIEW: More than a century of hard rock mining has left a legacy of
      >160,000 abandoned mines in the Western USA that are home to the majority of
      Native American lands. This article describes how abrogation of treaty rights,
      ineffective policies, lack of infrastructure, and a lack of research in Native
      communities converge to create chronic exposure, ill-defined risks, and tribal
      health concerns. RECENT FINDINGS: Recent results show that Native Americans
      living near abandoned uranium mines have an increased likelihood for kidney
      disease and hypertension, and an increased likelihood of developing multiple
      chronic diseases linked to their proximity to the mine waste and activities
      bringing them in contact with the waste. Biomonitoring confirms higher than
      expected exposure to uranium and associated metals in the waste in adults,
      neonates, and children in these communities. These sites will not be cleaned up
      for many generations making it critical to understand and prioritize exposure
      toxicity relationships in Native populations to appropriately allocate limited
      resources to protect health. Recent initiatives, in partnership with Native
      communities, recognize these needs and support development of tribal research
      capacity to ensure that research respectful of tribal culture and policies can
      address concerns in the future. In addition, recognition of the risks posed by
      these abandoned sites should inform policy change to protect community health in
      the future.

PMID- 28447317
TI  - Neuroimaging findings of postnatally acquired Zika virus infection: a pictorial
      essay.
AB  - Zika virus (ZIKV) is a mosquito-borne arbovirus from the Flaviviridae family,
      first discovered in 1947. There has been no report of severe complications caused
      by this virus in humans until recently. However, it is confirmed now that
      prenatally acquired ZIKV infection may cause severe congenital brain
      abnormalities in the infected fetuses. In addition, there has been an increasing
      number of reports during recent years about the causal relationship between
      postnatally acquired ZIKV infection and severe neurologic complications (mostly
      immune-mediated ones). Hence, ZIKV should not be considered as benign as it was
      initially thought, but it might be seen as a serious global threat to human
      health that may severely affect not only fetuses. In this pictorial essay, we aim
      to describe and illustrate the currently recognized spectrum of neuroimaging
      findings in postnatally acquired ZIKV infection. Although neurologic
      complications do not frequently occur in postnatal ZIKV infection, it is
      important to be aware of them because they may cause high morbidity and mortality
      in the affected patients. In addition to clinical and laboratory findings,
      neuroimaging may help in the diagnostic work-up to make the correct diagnosis,
      determine the extent of the disease, and follow the clinical course.

PMID- 28447318
TI  - Erector spinae plane block for postoperative analgesia in pediatric oncological
      thoracic surgery.

PMID- 28447319
TI  - [Effects of Geriatric COPD rehabilitation on hospital admissions and exercise
      tolerance: a retrospective observational study].
AB  - INTRODUCTION: Frail COPD patients are frequently not accepted for regular
      pulmonary rehabilitation programs due to low physical condition and functional
      limitations. Rehabilitation programs in nursing homes for geriatric patients with
      COPD have been developed. The effects of such programs are largely unknown. AIMS:
      To assess the course of COPD-related hospital admissions and exercise tolerance
      in a cohort of frail COPD patients participating in geriatric COPD
      rehabilitation. METHODS: Retrospective observational study with a follow up of 12
      months after discharge from rehabilitation. COPD related hospital admission days
      were measured in the year before and after participating rehabilitation. Exercise
      tolerance was measured by the six minute walk test (6MWT) at admission and at
      discharge from rehabilitation. RESULTS: Fifty-eight participants accomplished the
      rehabilitation program. Twelve patients died in the first year after discharge.
      The median number of hospital admission days in the year before participating
      rehabilitation was 21 (IQR 10-33). The first year after discharge this was
      decreased to a median of 6 (IQR 0-12). The 6MWT increased from 194 (SD 85) meters
      at admission to 274 (SD 95) meters at discharge (mean difference 80 m, SD 72; p <
      0.05). CONCLUSIONS: Geriatric COPD rehabilitation in a nursing home setting seems
      to reduce hospital admissions in frail COPD patients and to increase exercise
      tolerance.

PMID- 28447320
TI  - Should Ablation Be First-Line Therapy for Patients with Paroxysmal AF?
AB  - OPINION STATEMENT: Atrial fibrillation is the most common cardiac arrhythmia and
      the number of patients is expected to continuously increase in the next years.
      Catheter ablation is an effective, safe, and well-established treatment for
      patient with symptomatic and drug-resistant paroxysmal atrial fibrillation (PAF).
      Over the last decade, there was an increasing body of evidence demonstrating
      superiority of catheter ablation over antiarrhythmic drugs (AADs) in maintaining
      sinus rhythm. However, randomized clinical trials have not been conclusive to
      consider catheter ablation as a first-line therapy for PAF. The encouraging
      results of RAAFT Trial were not confirmed in the MANTRA-PAF Trial and in the
      RAAFT-2 Trial. Recent meta-analyses showed that catheter ablation is more
      effective than AAD therapy as a first-line treatment for PAF. In particular,
      relatively young patients and patients with no or minimal cardiovascular disease
      are the subpopulation that benefitted more from catheter ablation. On the other
      hand, the meta-analysis showed that catheter ablation causes more severe side
      effects than AAD therapy, underling the importance of patient selection and
      operator experience. To date, there are no univocal evidences to consider
      catheter ablation as a first-line therapy for PAF. Apart from patients'
      preference and avoidance of toxicity of AADs, the published data are supportive
      to consider a first-line catheter ablation in a peculiar subpopulation of
      patients. In particular, younger patients, patients with sinus node dysfunction
      related to AF, and patients with tachycardiomyopathy are the subgroups that seem
      to be good candidates for catheter ablation as a first-line therapy for PAF.

PMID- 28447321
TI  - Erratum to: Population dynamics among six major groups of the Oryza rufipogon
      species complex, wild relative of cultivated Asian rice.

PMID- 28447322
TI  - Successful hepatectomy for hepatic abscess with chronic granulomatous disease: a
      case report.
AB  - BACKGROUND: Chronic granulomatous disease (CGD), a rare inherited disorder, is
      characterized by impaired ability of phagocytic cells to kill certain bacteria
      and fungi. Although liver abscess is a common manifestation of CGD, its optimal
      management in these patients is unknown. Here, we present a case of successful
      hepatectomy for hepatic abscess in a patient with CGD. CASE PRESENTATION: An
      adolescent patient with previously diagnosed CGD presented to the pediatrics
      department of our institution with fever. Blood tests showed high concentrations
      of inflammatory markers. A computed tomography (CT) scan showed a multilocular
      mass measuring 52 mm * 34 mm in hepatic segment 4 (S4). Blood cultures were
      negative. Despite administration of antibiotics and gamma-globulin, his fever and
      high concentrations of inflammatory markers persisted and the mass did not change
      on CT scan images. Because the medications had proved ineffective and
      percutaneous drainage would have been difficult because of the honeycombing in
      the abscess, we performed hepatic S4a + S5 anatomic resection and
      cholecystectomy. Culture of the excised specimen was negative. The patient's
      postoperative course was uneventful. On day 62, CT showed no abscess around the
      resection stump. On day 81, he was transferred to undergo bone marrow
      transplantation. CONCLUSIONS: Surgical treatment for hepatic abscess can be
      effective when medical treatment has failed.

PMID- 28447323
TI  - Observation of Clinically Relevant Drug Interaction in Chimeric Mice with
      Humanized Livers: The Case of Valproic Acid and Carbapenem Antibiotics.
AB  - BACKGROUND AND OBJECTIVE: Human in vitro and dog in vitro/in vivo researches
      indicate that the drug-drug interaction (DDI) of decreased plasma valproic acid
      (VPA) concentration by co-administration of carbapenem antibiotics is caused by
      inhibition of acylpeptide hydrolase (APEH)-mediated VPA acylglucuronide (VPA-G)
      hydrolysis by carbapenems. In this study, we investigated VPA disposition and
      APEH activities in TK-NOG chimeric mice, whose livers were highly replaced with
      human hepatocytes, to evaluate the utility of this animal model and the clinical
      relevance of the DDI mechanism. METHODS: VPA and VPA-G concentrations in plasma,
      urinary excretion of VPA-G and APEH activity in humanized livers were measured
      after co-administration of VPA with meropenem (MEPM) to chimeric mice. RESULTS:
      After co-administration with MEPM to the chimeric mice, plasma VPA concentration
      more rapidly decreased than without the co-administration. An increase in plasma
      AUC and urinary excretion of VPA-G was also observed. APEH activity in humanized
      livers was strongly inhibited even at 24 h after co-administration of MEPM to the
      chimeric mice. CONCLUSION: The DDI of VPA with carbapenems was successfully
      observed in chimeric mice with humanized livers. The DDI was caused by long
      lasting inhibition of hepatic APEH-mediated VPA-G hydrolysis by carbapenems,
      which strongly supports the APEH-mediated mechanism of the clinical DDI. This is
      the first example showing the usefulness of chimeric mice with humanized livers
      for evaluation of a DDI via non-cytochrome P450 enzyme.

PMID- 28447324
TI  - Craniofacial morphology and dental maturity in children with reduced somatic
      growth of different aetiology and the effect of growth hormone treatment.
AB  - Children with reduced somatic growth may present various endocrinal diseases,
      especially growth hormone deficiency (GHD), idiopathic short stature (ISS),
      chromosomal aberrations, or genetic disorders. In an attempt to normalize the
      short stature, growth hormone (GH) is administered to these children. The aim of
      this literature review was to collect information about the craniofacial
      morphology and dental maturity in these children and to present the existing
      knowledge on the effect of GH treatment on the above structures.This review
      demonstrated that regardless of the origin of the somatic growth retardation,
      these children show similar craniofacial features, such as short length of the
      cranial base and the mandible, increased lower facial height, retropositioned
      mandible, and obtuse gonion angle. On the other hand, dental maturation does not
      demonstrate a specific pattern. Except for the above findings, muscle alterations
      seem to be present in individuals with short stature, who present low body muscle
      mass and strength, while studies on their craniofacial muscles seem to be
      lacking. After GH administration, the exact amount and pattern of craniofacial
      growth is unpredictable; however, the facial convexity decreases, mandibular
      length increases, and posterior facial height increases, while tooth eruption
      remains unaffected. Thus, it is of great importance to gain more insight into the
      craniofacial growth of treated and untreated children with reduced somatic growth
      so that the influence of GH therapy on the various craniofacial structures could
      be ascertained and proper orthodontic treatment could be selected.

PMID- 28447325
TI  - Interferon-free therapy with sofosbuvir plus ribavirin for successful treatment
      of genotype 2 hepatitis C virus with lichen planus: a case report.
AB  - Hepatitis C virus (HCV) infection remains the main cause of liver disease and can
      lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV may also
      develop extrahepatic manifestations in the skin, eyes, joints, kidneys, nervous
      system, and immune system. In fact, several studies reported that up to 70% of
      HCV patients experienced extrahepatic manifestations. Lichen planus (LP), which
      is an immune system disorder that is triggered by viral infections, allergens,
      and stress, can affect the skin, mouth, nails, and scalp. The association of LP
      with HCV has been reported, but the effect of HCV treatment on LP remission is
      controversial. We encountered a 53-year-old man with HCV genotype 2a and LP that
      were successfully treated with sofosbuvir and ribavirin for 12 weeks. After
      treatment, he achieved sustained virological response against HCV and remission
      of erosive LP lesions on the lip. In the era of interferon (IFN)-based treatment
      for HCV, exacerbation of autoimmune diseases is a common adverse event.
      Therefore, use of an IFN-free regimen of direct-acting antivirals for HCV might
      prevent the extrahepatic manifestation of an immune disorder.

PMID- 28447326
TI  - CT colonography: role in FOBT-based screening programs for colorectal cancer.
AB  - Computed tomographic colonography (CTC) is a minimally invasive imaging
      examination for the colon, and is safe, well tolerated and accurate for the
      detection of colorectal cancer (CRC) and advanced adenoma. While the role of CTC
      as a primary test for population screening of CRC is under investigation, the
      fecal occult blood test (FOBT) has been recommended for population screening of
      CRC in Europe. Subjects with positive FOBT are invited to undergo total
      colonoscopy, which has some critical issues, such as suboptimal compliance,
      contraindications and the possibility of an incomplete exploration of the colon.
      Based on available data, the integration of CTC in FOBT-based population
      screening programs for CRC may fall into three scenarios. First, CTC is
      recommended in FOBT-positive subjects when colonoscopy is refused, incomplete or
      contraindicated. For these indications CTC should replace double-contrast barium
      enema. Second, conversely, CTC is not currently recommended as a second-level
      examination prior to colonoscopy in all FOBT-positive subjects, as this strategy
      is most probably not cost-effective. Finally, CTC may be considered instead of
      colonoscopy for surveillance after adenoma removal, but specific studies are
      needed.

PMID- 28447327
TI  - Uptake of 123I-metaiodobenzylguanidine by gastrointestinal stromal tumor.
AB  - A 52-year-old woman was admitted with a large intraabdominal mass. 123I-
      metaiodobenzylguanidine (123I-MIBG) scintigraphy revealed considerable 123I-MIBG
      accumulation by the mass that was compatible with a diagnosis of paraganglioma.
      However, a spindle cell tumor that was identified using endoscopic ultrasound
      guided fine needle aspiration before surgery was positive for CD117. The
      surgically resected mass was confirmed as a gastrointestinal stromal tumor
      (GIST). Although the mechanism of 123I-MIBG uptake by GIST has not been
      elucidated, GIST should be included in the differential diagnosis of intra
      abdominal tumor with 123I-MIBG uptake.

PMID- 28447328
TI  - Utility of Doppler ultrasonography for diagnosing and assessing treatment effects
      in liver compartment syndrome.
AB  - Liver compartment syndrome is a life-threatening complication of hepatic
      subcapsular hematoma; diagnosis and assessment of treatment effects are therefore
      important. We report a rare case of liver compartment syndrome due to spontaneous
      hepatic subcapsular hematoma without any underlying conditions, in which Doppler
      ultrasonography (US) proved useful in both diagnosis and assessment of treatment
      effects. A 32-year-old woman experienced sudden epigastralgia and was diagnosed
      with hepatic subcapsular hematoma in the right lobe, based on contrast-enhanced
      computed tomography. Hepatic arteriography showed active hemorrhage and Doppler
      US showed retrograde flow in the right portal vein. From these findings, we
      diagnosed hepatic subcapsular hematoma complicated with liver compartment
      syndrome, and performed embolization of the bleeding point and percutaneous
      hematoma drainage. After these medical procedures, normalized antegrade flow in
      the right portal vein was observed on Doppler US. No underlying conditions
      contributing to hematoma were identified. In this case, Doppler US was useful for
      both diagnosis and assessment of treatment effects in liver compartment syndrome.
      When we examine patients with hepatic subcapsular hematoma, Doppler US should be
      used to diagnose the presence of liver compartment syndrome and assess treatment
      effects.

PMID- 28447329
TI  - Immune Response Against Salmonella Enteritidis Is Unsettled by HIV Infection.
AB  - The human immunodeficiency virus (HIV) is responsible for more than 2 million new
      infections per year and opportunistic infections such as Salmonella spp.
      Gastroenteritis is an important cause of mortality and morbidity in developing
      countries. Monocytes and macrophages play a critical role in the innate immune
      response against bacterial infections. However during HIV infection the virus can
      infect these cells and although they are more resistant to the cytopathic
      effects, they represent an important viral reservoir in these patients. Our aim
      was to evaluate the monocyte functions from HIV-1 infected patients after in
      vitro exposition to Salmonella Enteritidis. Our results suggest impairment of
      monocytes phagocytic and microbicidal activity in HIV-1 non-treated patients,
      which was more evident in women, if compared with men. Moreover, monocytes from
      HIV-1 infected and non-treated patients after stimulation with the bacteria,
      produced more pro-inflammatory cytokines than monocytes from HIV-treated
      patients, suggesting that HIV-1 infected patients have their functions
      unbalanced, once in the presence of an opportunistic infection in vitro.

PMID- 28447330
TI  - Seawater drowning-associated pneumonia: a 10-year descriptive cohort in intensive
      care unit.
AB  - BACKGROUND: Pneumonia is one of the major complications of drowning, but the
      optimal empirical antibiotic treatment is not clearly defined. Multidrug
      resistant (MDR) bacteria and fungi have been identified in a recent series of
      freshwater drowning-associated pneumonia. However, microbial data in seawater
      drowning are scarce. The objective of the study is to describe the microorganisms
      isolated in early respiratory specimens obtained from seawater drowning
      associated pneumonia and to provide their antibiotic susceptibility pattern.
      METHODS: All patients admitted for seawater drowning between 2003 and 2013 to two
      intensive care units, from the region in France with the highest drowning rate,
      were retrospectively included. Demographics, antimicrobial therapy and
      microbiological data from respiratory samples collected within the first 48 h
      after admittance were analyzed. RESULTS: Seventy-four drowned patients were
      included, of which 36 (49%) were diagnosed by the clinician as having early
      pneumonia. Concerning the overall population, the median simplified acute
      physiology score (version 2) was 45 (30-65), and the mortality was 26%. Twenty
      four respiratory samples from different patients were obtained within the first
      48 h. Sixteen were positive. The main microorganisms found were
      Enterobacteriaceae (Enterobacter spp., Klebsiella spp. and Escherichia coli) and
      Gram-positive aerobic cocci (Streptococcus pneumonia and Staphylococcus aureus)
      with a low rate of antimicrobial resistance. No MDR bacteria or fungi were
      identified. However, among the positive respiratory samples collected, 5/16 (31%)
      grew bacteria with natural resistance to amoxicillin-clavulanate, the first-line
      antibiotic commonly used in our cohort. Resistance was only found among Gram
      negative bacteria and from respiratory samples of patients with a higher drowning
      grade at admission (p = 0.01). CONCLUSIONS: This 10-year descriptive study, the
      largest cohort to date, provides early respiratory samples from seawater drowning
      patients. The microorganisms retrieved were either mostly part of the human oro
      pharyngeal flora or Enterobacteriaceae and displayed low rates of antimicrobial
      resistance. Respiratory samples should nonetheless be collected at admittance to
      the ICU to avoid inappropriate treatment. Empiric use of cephalosporin could be
      restricted to severe patients or if Gram-negative bacilli are found after direct
      examination.

PMID- 28447331
TI  - Understanding Action and Adventure Sports Participation-An Ecological Dynamics
      Perspective.
AB  - Previous research has considered action and adventure sports using a variety of
      associated terms and definitions which has led to confusing discourse and
      contradictory research findings. Traditional narratives have typically considered
      participation exclusively as the pastime of young people with abnormal
      characteristics or personalities having unhealthy and pathological tendencies to
      take risks because of the need for thrill, excitement or an adrenaline 'rush'.
      Conversely, recent research has linked even the most extreme forms of action and
      adventure sports to positive physical and psychological health and well-being
      outcomes. Here, we argue that traditional frameworks have led to definitions,
      which, as currently used by researchers, ignore key elements constituting the
      essential merit of these sports. In this paper, we suggest that this lack of
      conceptual clarity in understanding cognitions, perception and action in action
      and adventure sports requires a comprehensive explanatory framework, ecological
      dynamics which considers person-environment interactions from a multidisciplinary
      perspective. Action and adventure sports can be fundamentally conceptualized as
      activities which flourish through creative exploration of novel movement
      experiences, continuously expanding and evolving beyond predetermined
      environmental, physical, psychological or sociocultural boundaries. The outcome
      is the emergence of a rich variety of participation styles and philosophical
      differences within and across activities. The purpose of this paper is twofold:
      (a) to point out some limitations of existing research on action and adventure
      sports; (b) based on key ideas from emerging research and an ecological dynamics
      approach, to propose a holistic multidisciplinary model for defining and
      understanding action and adventure sports that may better guide future research
      and practical implications.

PMID- 28447332
TI  - Response to letters by Baethge et al. and Martino et al.

PMID- 28447333
TI  - Efficacy and tolerability of lithium in treating acute mania in youth with
      bipolar disorder: protocol for a systematic review.
AB  - BACKGROUND: Epidemiological, clinical, and high-risk studies have provided
      evidence that the peak period for onset of diagnosable episodes of mania and
      hypomania starts in mid-to-late adolescence. Moreover, clinically significant
      manic symptoms may occur even earlier, especially in children at familial risk.
      Lithium is the gold standard treatment for acute mania in adults, yet to our
      knowledge, there is no published systematic review assessing lithium treatment of
      mania in children or adolescents. This is a major gap in knowledge needed to
      inform clinical practice. AIM: As a working group within the ISBD Task Force on
      Lithium Treatment ( http://www.isbd.org/active-task-forces ), our aim is to
      complete a systematic review of the efficacy, tolerability, and acceptability of
      lithium compared with placebo and other active drugs in treating mania in
      children and adolescents diagnosed with bipolar disorder. METHODS: We will
      include double- or single-blind randomized controlled trials in patients aged
      less than 18 years. No restrictions will be made by study publication date or
      language. Several electronic databases will be searched along with secondary
      sources such as bibliographies and trial registry websites for published and
      unpublished studies. Response rates to lithium compared with placebo or other
      active drugs will be the primary efficacy outcome. Primary tolerability and
      acceptability outcomes will be rates of serious adverse events and dropouts,
      respectively. Secondary outcomes will include rates of remission, severity of
      manic symptoms at different time points, and incidence of specific adverse
      events. DISCUSSION: Findings from this systematic review are critically needed to
      inform clinical practice. We should not generalize findings from adult studies,
      as children and adolescents are undergoing accelerated physiological and brain
      development. Therefore, efficacy, tolerability, and acceptability of lithium
      treatment of acute mania in children compared to adults may be very different.
      This systematic review has been registered in PROSPERO (CRD42017055675).

PMID- 28447334
TI  - 1H-NMR, 1H-NMR T2-edited, and 2D-NMR in bipolar disorder metabolic profiling.
AB  - BACKGROUND: The objective of this study was to identify molecular alterations in
      the human blood serum related to bipolar disorder, using nuclear magnetic
      resonance (NMR) spectroscopy and chemometrics. METHODS: Metabolomic profiling,
      employing 1H-NMR, 1H-NMR T2-edited, and 2D-NMR spectroscopy and chemometrics of
      human blood serum samples from patients with bipolar disorder (n = 26) compared
      with healthy volunteers (n = 50) was performed. RESULTS: The investigated groups
      presented distinct metabolic profiles, in which the main differential metabolites
      found in the serum sample of bipolar disorder patients compared with those from
      controls were lipids, lipid metabolism-related molecules (choline, myo-inositol),
      and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic
      acid, L-glutamine). In addition, amygdalin, alpha-ketoglutaric acid, and
      lipoamide, among other compounds, were also present or were significantly altered
      in the serum of bipolar disorder patients. The data presented herein suggest that
      some of these metabolites differentially distributed between the groups studied
      may be directly related to the bipolar disorder pathophysiology. CONCLUSIONS: The
      strategy employed here showed significant potential for exploring
      pathophysiological features and molecular pathways involved in bipolar disorder.
      Thus, our findings may contribute to pave the way for future studies aiming at
      identifying important potential biomarkers for bipolar disorder diagnosis or
      progression follow-up.

PMID- 28447335
TI  - Positive alcohol expectancies mediate associations between ADHD behaviors and
      alcohol-related problems among college students.
AB  - An increasing percentage of college students report being affected by ADHD
      behaviors, and this population is at increased risk of experiencing negative
      consequences associated with alcohol consumption. However, specific factors
      motivating alcohol consumption and contributing to negative outcomes among these
      individuals are not well understood. Recent work suggests alcohol expectancies
      may interact with ADHD behaviors to influence negative drinking-related outcomes
      among those with elevated inattention and/or hyperactivity-impulsivity. Seven
      hundred-forty emerging adults (M age = 19.13 [SD = 2.25] years; 72.1% female;
      85.8% Caucasian) enrolled in two public universities in the Southeast and Midwest
      USA completed the Brief Comprehensive Effects of Alcohol Survey (B-CEOA) and
      provided self-reports of ADHD symptoms and drinking-related outcomes. Multiple
      mediation analyses were conducted to evaluate effects of ADHD behaviors (i.e.,
      hyperactivity-impulsivity, and inattention) and related impairment in major life
      domains (e.g., social interactions, occupational and educational activities,
      fulfillment of daily responsibilities) on drinking-related outcomes via positive
      and negative alcohol expectancies, controlling for sex, age, co-occurring
      oppositional behaviors, and data collection site. Inattention, hyperactivity
      impulsivity, and impairment directly predicted both personal and social problems
      consequent to alcohol use. Effects of ADHD behaviors and impairment on drinking
      related personal and social problems were partially mediated by positive
      expectancies. Findings are consistent with and extend prior work supporting a
      role of positive alcohol expectancies in alcohol-related negative outcomes among
      college students experiencing mild to moderate symptoms of ADHD.

PMID- 28447336
TI  - Review of recent molecular landscape knowledge of gastric cancer.
AB  - Gastric cancer (GC) is one of the most frequently diagnosed cancers worldwide and
      its prognosis remains dismal. One reason for poor outcomes of GC patients is that
      most are diagnosed when the cancer has already advanced. Novel biomarkers with
      high sensitivity and specificity are needed to diagnose GC in the early stage. In
      addition, to improve the outcome of patients with GC, patient stratification
      according to prognostic factors and sensitivity to chemo(radio)therapy are
      necessary. Appropriate follow-up criteria and individualized treatment will
      contribute to improvement in prognosis. Over the past decades, development of
      microarray and sequencing technology have coalesced to increase reports regarding
      epigenetic alterations that affect the character of malignancies including GC.
      These advances help our understanding of gastric carcinogenesis and have the
      possibility of improving the prognosis of GC by contributing to the optimization
      of therapeutic strategies. Further development of biomarkers for diagnosis and
      prognosis are desperately needed. Here, we enumerate and describe some GC-related
      molecules reported over the past few years that may be useful biomarkers.

PMID- 28447338
TI  - CORRIGENDUM.

PMID- 28447337
TI  - Reconstructing the ancestral vertebrate brain.
AB  - Highly complicated morphologies and sophisticated functions of vertebrate brains
      have been established through evolution. However, the origin and early
      evolutionary history of the brain remain elusive, owing to lack of information
      regarding the brain architecture of extant and fossil species of jawless
      vertebrates (agnathans). Comparative analyses of the brain of less studied
      cyclostomes (only extant agnathan group, consisting of lampreys and hagfish) with
      the well-known sister group of jawed vertebrates (gnathostomes) are the only
      tools we have available to illustrate the ancestral architecture of the
      vertebrate brain. Previous developmental studies had shown that the lamprey
      lacked well-established brain compartments that are present in gnathostomes, such
      as the medial ganglionic eminence and the rhombic lip. The most accepted scenario
      suggested that cyclostomes had fewer compartments than that of the gnathostome
      brain and that gnathostomes thus evolved by a stepwise addition of innovations on
      its developmental sequence. However, recent studies have revealed that these
      compartments are present in hagfish embryos, indicating that these brain regions
      have been acquired before the split of cyclostomes and gnathostomes. By comparing
      two cyclostome lineages and gnathostomes, it has become possible to speculate
      about a more complex ancestral state of the brain, excluding derived traits in
      either of the lineages. In this review, we summarize recent studies on the brain
      development of the lamprey and hagfish. Then, we attempt to reconstruct the
      possible brain architecture of the last common ancestor of vertebrates. Finally,
      we discuss how the developmental plan of the vertebrate brain has been modified
      independently in different vertebrate lineages.

PMID- 28447339
TI  - Activity of anti-inflammatory, analgesic and antigenotoxic of the aqueous flower
      extracts of Opuntia microdasys Lem.Pfeiff.
AB  - OBJECTIVES: The aim of this study was to evaluate the analgesic and the anti
      inflammatory activity of Opuntia microdasys at post flowering stage, F3 (OMF3) in
      rat and, in other hand, its antigenotoxic effects by the Allium cepa test.
      METHODS: OMF3 extracts were screened for activity of analgesic and anti
      inflammatory using, respectively, the acetic acid writhing test in mice and the
      carrageenan-induced paw oedema assay in rats. The antigenotoxic has been
      evaluated by A. cepa test. KEY FINDINGS: OMF3 extracts showed a higher analgesic
      and anti-inflammatory activity at 100 mg/kg (72.03% and 70.11%) as determined by
      the tests of acetic acid-induced writhing and carrageenan-induced oedema,
      respectively. Furthermore, the OMF3 aqueous extracts have a preventive
      antimutagenic potential, at lower concentration (EC50 ~ 60 MUg/ml), against H2 O2
      -mediated DNA damage in A. cepa root meristem cells with an efficient restoration
      of the mitotic index in comparison with controls. CONCLUSIONS: Based on this
      study, the flower of O. microdasys at post flowering stage may be use as an
      analgesic, anti-inflammatory and antimutagenic agents.

PMID- 28447340
TI  - Marginal deficiencies of dietary arginine and methionine could suppress growth
      performance and immunological responses in broiler chickens.
AB  - The present study was conducted to investigate the effects of different levels of
      dietary arginine (Arg) and methionine (Met) on performance, immune responses, and
      carcass characteristics of broiler chickens. A total of 540 day-old Ross 308
      broiler chicks were randomly assigned into the nine experimental diets,
      consisting five replicates of 12 birds each. Dietary treatments included three
      different levels (90%, 100%, and 110% of National Research Council [NRC]
      specifications) of either dietary Arg or Met, which were fed to the birds
      according to a 3 * 3 factorial arrangement of treatments during a 42 days feeding
      trial. Results showed that supplementation of Arg and Met into the deficient
      diets increased (p < .01) weight gains during all trial periods. Although average
      daily feed intake (ADFI) was not influenced by dietary treatments, increasing Arg
      up to 100% of NRC recommendations improved (p < .05) feed conversion ratio (FCR)
      throughout the trial period. Similarly, supplementation of deficient-diets with
      Met improved FCR values. There was a significant (p < .01) Arg * Met interaction
      for ADFI during the starter period; increasing the dietary Arg level increased
      ADFI when the diets were deficient in Met, while had an opposite effect in diets
      containing higher dietary Met levels. On the other hand, dietary Met
      fortification improved (p = .067) FCR values to a greater extent in 110% Arg
      diets during the entire trial period. Although different levels of Arg and Met
      had no marked effects on carcass yield and abdominal fat percentage, supplemental
      Arg up to 100% of NRC values increased (p < .01) the relative weights of spleen
      and bursa of Fabricius. Furthermore, bursa weight was affected by Arg * Met
      interaction (p < .01), so that supplemental Arg level of 100% of NRC increased
      the relative bursa weight in birds that were fed diets containing 90% and 110% of
      Met. Serum uric acid level was decreased (p < .05) as a result of dietary Arg
      fortification up to 110% of NRC recommended values. Supplementation of deficient
      diets with Met decreased (p < .05) serum cholesterol level. Although Newcastle
      antibody titer was not affected by dietary Arg or Met levels, Arg fortification
      of deficient-diets increased (p < .001) antibody responses against infectious
      bronchitis (IBV) and bursal (IBD) disease viruses. Similarly, Met supplementation
      of deficient-diets increased IBD antibody titer. There were significant (p < .05)
      Arg * Met interactions for IBV and IBD titers; Met fortification of 110% Arg
      diets was more effective in increasing antibody titers. An increase in dietary
      Met level up to 100% of NRC values increased (p < .001) serum concentration of
      gamma-globulins. The present findings imply that supplemental Arg could affect
      feed efficiency and antibody responses when the diets were already fortified with
      a sufficient Met level.

PMID- 28447341
TI  - Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early
      stage Hodgkin lymphoma.
AB  - BACKGROUND: Combined modality treatment consisting of chemotherapy followed by
      localised radiotherapy is the standard treatment for patients with early stage
      Hodgkin lymphoma (HL). However, due to long- term adverse effects such as
      secondary malignancies the role of radiotherapy has been questioned recently and
      some clinical study groups advocate chemotherapy only for this indication.
      OBJECTIVES: To assess the effects of chemotherapy alone compared to chemotherapy
      plus radiotherapy in adults with early stage HL . SEARCH METHODS: For the or i
      ginal version of this review, we searched MEDLINE, Embase and CENTRAL as well as
      conference proceedings (American Society of Hematology, American Society of
      Clinical Oncology and International Symposium of Hodgkin Lymphoma) from January
      1980 to November 2010 for randomised controlled trials (RCTs) comparing
      chemotherapy alone versus chemotherapy regimens plus radiotherapy. For the
      updated review we searched MEDLINE, CENTRAL and conference proceedings to
      December 2016. SELECTION CRITERIA: We included RCTs comparing chemotherapy alone
      with chemotherapy plus radiotherapy in patients with early stage HL. We excluded
      trials with more than 20% of patients in advanced stage. As the value of
      radiotherapy in addition to chemotherapy is still not clear, we also compared to
      more cycles of chemotherapy in the control arm. In this updated review, we also
      included a second comparison evaluating trials with varying numbers of cycles of
      chemotherapy between intervention and control arms, same chemotherapy regimen in
      both arms assumed. We excluded trials evaluating children only, therefore only
      trials involving adults are included in this updated review. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed the
      quality of trials. We contacted study authors to obtain missing information. As
      effect measures we used hazard ratios (HR) for overall survival (OS) and
      progression-free survival (PFS) and risk ratios (RR) for response rates. Since
      not all trials reported PFS according to our definitions, we evaluated all
      similar outcomes (e.g. event-free survival) as PFS/tumour control. MAIN RESULTS:
      Our search led to 5518 potentially relevant references. From these, we included
      seven RCTs in the analyses involving 2564 patients. In contrast to the first
      version of this review including five trials, we excluded trials randomising
      children. As a result, we excluded one trial from the former analyses and we
      identified three new trials.Five trials with 1388 patients compared the
      combination of chemotherapy alone and chemotherapy plus radiotherapy, with the
      same number of chemotherapy cycles in both arms. The addition of radiotherapy to
      chemotherapy has probably little or no difference on OS (HR 0.48; 95% confidence
      interval (CI) 0.22 to 1.06; P = 0.07, moderate- quality evidence), however two
      included trials had potential other high risk of bias due to a high number of
      patients not receiving planned radiotherapy. After excluding these trials in a
      sensitivity analysis, the results showed that the combination of chemotherapy and
      radiotherapy improved OS compared to chemotherapy alone (HR 0.31; 95% CI 0.19 to
      0.52; P <0.00001, moderate- quality evidence). In contrast to chemotherapy alone
      the use of chemotherapy and radiotherapy improved PFS (HR 0.42; 95% CI 0.25 to
      0.72; P = 0.001; moderate- quality evidence). Regarding infection- related
      mortality (RR 0.33; 95% CI 0.01 to 8.06; P = 0.5; low- quality evidence), second
      cancer- related mortality (RR 0.53; 95% CI 0.07 to 4.29; P = 0.55; low- quality
      evidence) and cardiac disease- related mortality (RR 2.94; 95% CI 0.31 to 27.55;
      P = 0.35;low- quality evidence), there is no evidence for a difference between
      the use of chemotherapy alone and chemotherapy plus radiotherapy. For complete
      response rate (CRR) (RR 1.08; 95% CI 0.93 to 1.25; P = 0.33; low- quality
      evidence), there is also no evidence for a difference between treatment
      groups.Two trials with 1176 patients compared the combination of chemotherapy
      alone and chemotherapy plus radiotherapy, with different numbers of chemotherapy
      cycles in both arms. OS is reported in one trial only, the use of chemotherapy
      alone (more chemotherapy cycles) may improve OS compared to chemotherapy plus
      radiotherapy (HR 2.12; 95% CI 1.03 to 4.37; P = 0.04; low- quality evidence).
      This trial also had a potential other high risk of bias due to a high number of
      patients not receiving planned therapy. There is no evidence for a difference
      between chemotherapy alone and chemotherapy plus radiotherapy regarding PFS (HR
      0.42; 95% CI 0.14 to 1.24; P = 0.12; low- quality evidence). After excluding the
      trial with patients not receiving the planned therapy in a sensitivity analysis,
      the results showed that the combination of chemotherapy and radiotherapy improved
      PFS compared to chemotherapy alone (HR 0.24; 95% CI 0.070 to 0.88; P = 0.03,
      based on one trial). For infection- related mortality (RR 6.90; 95% CI 0.36 to
      132.34; P = 0.2; low- quality evidence), second cancer- related mortality (RR
      2.22; 95% CI 0.7 to 7.03; P = 0.18; low- quality evidence) and cardiac disease
      related mortality (RR 0.99; 95% CI 0.14 to 6.90; P = 0.99; low-quality evidence),
      there is no evidence for a difference between the use of chemotherapy alone and
      chemotherapy plus radiotherapy. CRR rate was not reported. AUTHORS' CONCLUSIONS:
      This systematic review compared the effects of chemotherapy alone and
      chemotherapy plus radiotherapy in adults with early stage HL .For the comparison
      with same numbers of chemotherapy cycles in both arms, we found moderate- quality
      evidence that PFS is superior in patients receiving chemotherapy plus
      radiotherapy than in those receiving chemotherapy alone. The addition of
      radiotherapy to chemotherapy has probably little or no difference on OS . The
      sensitivity analysis without the trials with potential other high risk of bias
      showed that chemotherapy plus radiotherapy improves OS compared to chemotherapy
      alone.For the comparison with different numbers of chemotherapy cycles between
      the arms there are no implications for OS and PFS possible, because of the low
      quality of evidence of the results.

PMID- 28447342
TI  - Maintaining postharvest quality of cold stored 'Hass' avocados by altering the
      fatty acids content and composition with the use of natural volatile compounds -
      methyl jasmonate and methyl salicylate.
AB  - BACKGROUND: Low temperatures are often used to reduce metabolic processes and
      extend the storage life of fruit; however, in the case of avocado, a temperature
      below 3  degrees C will often result in the development of physiological
      disorders associated with chilling injury. The objective of this study was to
      investigate the ability of methyl jasmonate (MeJA) and methyl salicylate (MeSA)
      vapours to alleviate chilling injury in 'Hass' avocado fruit kept at 2  degrees C
      for 21 days followed by 6-7 days of shelf-life at 20  degrees C, simulating
      supply chain conditions. RESULTS: The incidence and severity of chilling injury
      were significantly reduced in MeJA- and MeSA-exposed fruit, especially at 100
      umol L-1 . The mechanism involved improved membrane integrity via alteration of
      the fatty acid content and composition, down-regulation of LOX gene expression
      and reduced activity of lipoxygenase. CONCLUSION: MeJA and MeSA have the
      potential for being used with 'Hass' avocado fruit shipped at low temperature to
      reduce its susceptibility to chilling injury. (c) 2017 Society of Chemical
      Industry.

PMID- 28447344
TI  - Short-term treatments with high CO2 and low O2 concentrations on quality of fresh
      goji berries (Lycium barbarum L.) during cold storage.
AB  - BACKGROUND: Goji berries (Lycium barbarum L.) are functional fruits but are
      usually marketed as a dried product. The aim of this study was to investigate the
      storability of fresh goji berries treated with high CO2 and low O2 concentrations
      before air storage at 1  degrees C for 21 days. RESULTS: Berries harvested
      without stems were exposed to air (controls) or subjected for 2 days at 1 
      degrees C to the following controlled atmosphere (CA) treatments: 21% O2 + 0% CO2
      (21+0), 5% O2 + 15% CO2 (5+15), 10% O2 + 10% CO2 (10+10) and 20% O2 + 20% CO2
      (20+20). During 14 days of storage, all treatments decreased weight loss, while
      treatments 5+15 and 20+20 prevented fungal decay. No fermentation was observed.
      The treatments did not affect color changes, decreases in soluble sugars and
      increases in total soluble solids, titratable acidity, ascorbic acid, total
      carotenoids, total phenolics and ferric-reducing antioxidant power (FRAP) during
      storage, apart from the marginally reduced FRAP by treatment 20+20 on day 7.
      Treatments 5+15, 10+10 and 20+20 resulted in residual decreases in respiration
      rates and pH values early during storage. After 14 days of storage, panelists
      rated the CA-treated samples as sweet, with good acceptance. CONCLUSION:
      Treatments 5+15 and 20+20 showed the best results after 14 days of storage. (c)
      2017 Society of Chemical Industry.

PMID- 28447343
TI  - Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS-55) on
      adiposity and hepatic lipid composition in rat offspring.
AB  - KEY POINTS: Fructose-containing sugars, including sucrose and high fructose corn
      syrup (HFCS), have been implicated in the epidemics of obesity and type 2
      diabetes. Few studies have evaluated the impact of perinatal exposure to these
      sugars on metabolic and physiological outcomes in the offspring. Using a rat
      model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal
      and/or suckling periods were found to have altered adiposity and liver fat
      content and composition at weaning. Plasma levels of free fatty acids remained
      elevated in young adulthood, but consumption of a control diet following weaning
      appeared to ameliorate most other effects of perinatal exposure to a maternal
      high-sugar diet. Guidelines for maternal nutrition should advise limiting
      consumption of fructose-containing sugars, and it is particularly important that
      these recommendations include maternal nutrition during lactation. ABSTRACT:
      Perinatal exposure to excess maternal intake of added sugars, including fructose
      and sucrose, is associated with an increased risk of obesity and type 2 diabetes
      in adult life. However, it is unknown to what extent the type of sugar and the
      timing of exposure affect these outcomes. The aim of this study was to determine
      the impact of exposure to maternal consumption of a 10% (w/v) beverage containing
      sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or
      suckling periods on offspring at 3 and 12 weeks, utilising a cross-fostering
      approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose
      concentrations in offspring at 3 weeks, but did not alter glucose tolerance.
      Increased adiposity was observed in 3-week-old offspring exposed to sucrose or
      HFCS-55 during suckling, with increased hepatic fat content in HFCS-55-exposed
      offspring. In terms of specific fatty acids, hepatic monounsaturated (omega-7 and
      -9) fatty acid content was elevated at weaning, and was most pronounced in
      sucrose offspring exposed during both the prenatal and suckling periods, and HFCS
      55 offspring exposed during suckling only. By 12 weeks, the effects on adiposity
      and hepatic lipid composition were largely normalised. However, exposure to
      either sucrose or HFCS-55 during the prenatal period only was associated with
      elevated plasma free fatty acids at weaning, and this effect persisted until 12
      weeks. This study suggests that the type of sugar and the timing of exposure
      (prenatal or suckling periods) are both important for determining the impact on
      metabolic health outcomes in the offspring.

PMID- 28447345
TI  - In vitro microbial protein synthesis, ruminal degradation and post-ruminal
      digestibility of crude protein of dairy rations containing Quebracho tannin
      extract.
AB  - This study evaluated the effects of Quebracho tannin extract (QTE) on in vitro
      ruminal fermentation, chemical composition of rumen microbes, ruminal degradation
      and intestinal digestibility of crude protein (iCPd). Three treatments were
      tested, the control (basal diet without QTE), the basal diet with 15 g QTE/kg dry
      matter (DM) and the basal diet with 30 g QTE/kg DM. The basal diet contained
      (g/kg DM): 339 grass silage, 317 maize silage and 344 concentrate. In vitro gas
      production kinetic was determined using the Hohenheim gas test (Experiment 1).
      The Ankom RF technique, a batch system with automatic gas pressure recordings,
      was used to determine in vitro production of short-chain fatty acids (SCFA) and
      ammonia-nitrogen concentration (NH3 -N), as well as nitrogen and purine bases
      content in liquid-associated microbes (LAM) and in a residue of undegraded feed
      and solid-associated microbes (Feed+SAM) (Experiment 2). Ruminal degradation and
      iCPd were determined using the nylon bag technique and the mobile nylon bag
      technique, respectively (Experiment 3). Gas production (Experiment 1), total SCFA
      and NH3 -N (Experiment 2) decreased with increasing QTE levels. Microbial mass
      and composition of LAM were not affected by QTE, but total mass of Feed+SAM
      linearly increased, likely due to decreased substrate degradation with increasing
      QTE levels. The total amount of N in microbial mass and undegraded feed after the
      in vitro incubation increased with increasing QTE levels, suggesting a potential
      greater N flow from the rumen to the duodenum. In contrast to in vivo studies
      with the same QTE, no effects were detected on ruminal effective degradability
      and iCPd, when using the nylon bag techniques. Based on the in vitro procedures,
      QTE increased the supply of N post-rumen; however, some evidence of a decreased
      fibre degradation were also observed. Therefore, the benefit of adding QTE to
      diets of cattle is still questionable.

PMID- 28447346
TI  - A charge equilibration formalism for treating charge transfer effects in MD
      simulations: Application to water clusters.
AB  - Conventional classical force fields by construction do not explicitly partition
      intermolecular interactions to include polarization and charge transfer effects,
      whereas fully quantum mechanical treatments allow a means to effect this
      dissection (although not uniquely due to the lack of a charge transfer operator).
      Considering the importance of polarization in a variety of systems, a particular
      class of classical models, charge equilibration models, have been extensively
      developed to study those systems; since these types of interaction models are
      inherently based on movement of charge throughout a system, they are natural
      platform for including polarization and charge transfer effects within the
      context of molecular simulations. Here, we present two bond-space charge
      equilibration models we term as QE2 and mixed QE2 treat charge transfer in
      classical molecular mechanical calculations those provide practical solutions to
      two major drawbacks of charge equilibration models: (a) a nonvanishing amount of
      charge transfer between two heteroatoms at large separations, and (b) superlinear
      polarizability scaling during bond dissociation due to charge transfer over
      unphysical, large distances. To control charge transfer during dissociation of a
      bond in a molecular system, we introduce a distance-dependent scaling function
      (QE2 model) which, controls and recovers physical behavior of the homonuclear and
      heteronuclear charge transfer between two atoms at small and large values of
      internuclear separation; and the mixed QE2 model in which we combine the QE2
      model under allow and disallow charge transfer situations that describe both
      charge transfer and polarizability in a distance-dependent manner. We demonstrate
      the utility of both models in the case of a water dimer, and compare the results
      with other existing models, and further, we perform short molecular dynamics
      simulations for few water clusters with the QE2 model to show the charge transfer
      and internuclear separation are correlated in dynamics. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28447348
TI  - Case of facial lupus erythematosus profundus with intractable ulceration
      successfully treated with dapsone.

PMID- 28447347
TI  - Abundance of the benign melanocytic universe: Dermoscopic-histopathological
      correlation in nevi.
AB  - The broad universe of "melanocytic nevi" includes a variety of different
      subtypes, which can be classified either due to their morphology, epidemiology,
      genetic alterations or risk for developing melanoma. Regarding morphology, on the
      one hand macroscopic/clinical and on the other hand histopathological appearance
      were used to subdivide in the past, often resulting in confusion and poor
      interobserver agreement, while nowadays dermoscopy presents the clinician's
      precious bridge between naked-eye examination and histopathological diagnostics,
      allowing prediction of the lesions' histopathology, follow up and monitoring over
      time without need of excision. The non-invasive dermoscopic examination relies on
      the assessment of colors, patterns and the distribution of both within a
      cutaneous lesion. Until today, the correspondence of certain dermoscopic colors
      and patterns to certain histopathological correlates has been reported for a huge
      amount of different cutaneous lesions. Moreover, the correspondence of certain
      dermoscopic features to certain body sites, age groups and pigmentary traits, but
      also to specific genetic alterations in lesions, has been broadly investigated.
      Dermoscopy has led us to a new understanding of melanocytic nevi's biology and
      evolution and, last but not least, to a new classification system, which we want
      to present herein.

PMID- 28447349
TI  - Review of vasculature visualized on dermoscopy.
AB  - Dermoscopy is a useful tool for finding and screening skin tumors, especially
      skin cancers. It is well known that it is useful to diagnose pigmented tumors,
      such as melanocytic lesions. In recent years, after the publication of a revised
      two-step algorithm in 2010, dermoscopy gradually has been used to diagnose non
      pigmented or non-melanocytic lesions based on their vascular structures. Some
      skin lesions have specific vascular structures that aid in diagnosis. In this
      review, I discuss the various patterns of the vascular structures and their
      distribution, focusing on their clinical importance and usefulness in daily
      medical treatment.

PMID- 28447350
TI  - Dermoscopy-pathology relationship in seborrheic keratosis.
AB  - Making a definitive diagnosis of seborrheic keratosis (SK) can be challenging for
      the naked eye due to its wide variation in clinical features. Fortunately,
      however, most cases of SK exhibit the typical dermoscopic findings of fissures
      and ridges, hairpin vessels with white halo, comedo-like openings, and milia-like
      cysts, all of which are helpful to distinguish SK from melanoma, melanocytic
      nevus, squamous cell carcinoma, basal cell carcinoma (BCC) and other skin tumors.
      Histopathologically, these dermoscopic characteristics correspond to
      papillomatous surface of the epidermis, enlarged capillaries of the dermal
      papillae, pseudohorn cysts in the epidermis opened to the surface of the lesion
      and intraepidermal cysts, respectively. Clinicians should bear in mind that the
      clonal type of SK dermoscopically mimics melanoma and BCC by the presence of
      globule-like structures, while regressing SK exhibits a granular pattern that is
      similar to the peppering found in melanoma. Furthermore, milia-like cysts alone
      are insufficient for a conclusive diagnosis of SK because melanoma in rare cases
      displays cysts along with other SK-like dermoscopic findings.

PMID- 28447351
TI  - Estimating melanin location in the pigmented skin lesions by hue-saturation
      lightness color space values of dermoscopic images.
AB  - The depth of melanin in the skin can be estimated roughly by observation of the
      color exhibited on dermoscopy. Currently, there are no objective methods to
      estimate it. The aim of the present study was to clarify the relationship between
      the depth of melanin in the skin and the color variation exhibited, and to
      objectively estimate the 3-D location of melanin in the pigmented skin lesions
      from dermoscopic images. Representative colors in dermoscopic images of acral
      compound nevus, Spitz nevus and blue nevus were evaluated by the subjectively
      perceived color on dermoscopy and objective values in hue-saturation-lightness
      color space values. Brown colors due to small quantities of superficial melanin
      in the skin had high saturation and low lightness values, whereas black colors
      due to large quantities of superficial melanin had low saturation and low
      lightness values. On the other hand, colors due to melanin in the dermis were
      perceived as blue-gray on dermoscopy, but extracted colors showed gray-brown hue
      and intermediate saturation and high lightness values. In all cases, extracted
      representative colors of pigmented skin lesions had similar hue values within the
      red-orange range. Objective estimation of the 3-D location of melanin in the
      pigmented skin lesions is possible by the saturation and lightness values of the
      colors extracted from dermoscopic images. Subjectively perceived colors of
      melanin, especially in the dermis, can be modified by the surrounding environment
      effect and blue color perception.

PMID- 28447352
TI  - Dermoscopic evaluation of melanonychia.
AB  - The prevalence of melanonychia is approximately 1%, and it is a common symptom
      encountered in daily practise. However, it may also be the first symptom of
      melanoma of the nail apparatus. Evaluation of adult melanonychia with clinical
      information and clinical images is sometimes difficult for clinicians.
      Dermoscopic observation provides important information based on the algorithm
      method. Melanonychia in children requires a different approach, because
      dermoscopic features observed in adult nail apparatus melanoma are generally
      observed in benign pediatric cases.

PMID- 28447354
TI  - Dermoscopy enhances insight into correct diagnosis.

PMID- 28447353
TI  - Candida albicans-induced pustular lesions in mice.

PMID- 28447355
TI  - Dermoscopy pathology correlation in melanoma.
AB  - Dermoscopy is a widely used technique whose role in the clinical (and
      preoperative) diagnosis of melanocytic and non-melanocytic skin lesions has been
      well established in recent years. The aim of this paper is to clarify the
      correlations between the "local" dermoscopic findings in melanoma and the
      underlying histology, in order to help clinicians in routine practice.

PMID- 28447357
TI  - Periodontitis and risk of psoriasis: another comorbidity.

PMID- 28447356
TI  - Eumycetoma caused by Trichophyton species successfully treated with terbinafine
      and surgery.

PMID- 28447358
TI  - Increased filaggrin expression in oral lichenoid lesions: is this cause or
      effect?

PMID- 28447359
TI  - Better data on psoriasis and psyche: but do they really reach the clinician?

PMID- 28447360
TI  - Recent progress in the understanding of relaxin family peptides and their
      receptors.
AB  - LINKED ARTICLES: This article is part of a themed section on Recent Progress in
      the Understanding of Relaxin Family Peptides and their Receptors. To view the
      other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc.

PMID- 28447361
TI  - The effect of dietary Chlorella vulgaris inclusion on goat's milk chemical
      composition, fatty acids profile and enzymes activities related to oxidation.
AB  - The impact of dietary supplementation with microalgae on goat's milk chemical
      composition, fatty acids (FA) profile and enzymes activities related to
      antioxidant mechanism has not been well documented. Thus, this study aimed to
      investigate the effects of dietary inclusion of Chlorella vulgaris on the
      following: (i) milk yield, chemical composition and FA profile, (ii) the
      activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase
      (GR), glutathione transferase (GST) and glutathione peroxidase (GSH-Px) in blood
      plasma and (iii) the activities of SOD, GR and lactoperoxidase (LPO) in milk of
      goats. Furthermore, the oxidative stress indicators for measuring total
      antioxidant and free radical scavenging activity [ferric reducing ability of
      plasma (FRAP) and 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)
      (ABTS) assays] and oxidative stress biomarkers [malondialdehyde (MDA) and protein
      carbonyls (PC)] were also determined in blood plasma and milk of the animals. For
      this purpose, 16 cross-bred goats were divided into two homogenous groups. Each
      goat of both groups was fed individually with alfalfa hay and concentrates
      separately. The concentrates of the control group (Control) had no microalgae,
      while those of the Chlorella group were supplemented with 10 g lyophilized
      Chlorella vulgaris/kg concentrates (Chlorella). Thus, the average intake was 5.15
      g Chlorella vulgaris/kg DM. The results showed that the dietary inclusion of
      Chlorella vulgaris had not noticeable impact on goat's milk yield, chemical
      composition and FA profile. Significantly higher SOD (by 10.31%) and CAT (by
      18.66%) activities in the blood plasma of goats fed with Chlorella vulgaris
      compared with the control were found. Moreover, the dietary supplementation with
      Chlorella vulgaris caused a significant increase in SOD (by 68.84%) activity and
      a reduction in PC (by 24.07%) content in goat's milk. In conclusion, the
      Chlorella vulgaris inclusion in goat's diets improved the antioxidant status of
      both animals and milk.

PMID- 28447362
TI  - Randomized, controlled trial split-faced study of 595-nm pulsed dye laser in the
      treatment of acne vulgaris and acne erythema in adolescents and early adulthood.
AB  - The high prevalence of acne vulgaris in teenagers has increased comorbidities.
      Lasers offer alternative options for acne treatment because they have rapid
      action, low systemic adverse effects, and do not require everyday treatment. To
      study the efficacy and patients' satisfaction of 595-nm pulse dye laser (PDL)
      treatment of acne vulgaris and acne erythema in adolescents and early adulthood,
      we designed a blocked-randomized, split-faced 595-nm PDL (fluence 8 J/cm3 pulse
      duration 10 ms, spot size 7 mm, 2 session every 2 weeks) study in patients with
      mild to moderate acne by comparing the laser-treated and non-treated side. The
      acne lesion counts, acne erythema grading, and acne severity grading were
      evaluated at baseline and 2, 4, and 8 weeks. Thirty patients were recruited. The
      results showed no statistically significant difference except the papule count at
      week 4 which was -1.828 on the treated side and 0.103 on the non-treated side of
      the face, P-value 0.0018. There was no statistically significant difference of
      acne severity grading and acne erythema grading between both sides of the face.
      The mean scores of patients' satisfaction on the laser-treated side were 75, 81,
      and 81%, respectively. The PDL treatment in this study reveals no significant
      improvement in acne therapy; however, the patients were satisfied with this laser
      treatment.

PMID- 28447363
TI  - Tobacco packaging design for reducing tobacco use.
AB  - BACKGROUND: Tobacco use is the largest single preventable cause of death and
      disease worldwide. Standardised tobacco packaging is an intervention intended to
      reduce the promotional appeal of packs and can be defined as packaging with a
      uniform colour (and in some cases shape and size) with no logos or branding,
      apart from health warnings and other government-mandated information, and the
      brand name in a prescribed uniform font, colour and size. Australia was the first
      country to implement standardised tobacco packaging between October and December
      2012, France implemented standardised tobacco packaging on 1 January 2017 and
      several other countries are implementing, or intending to implement, standardised
      tobacco packaging. OBJECTIVES: To assess the effect of standardised tobacco
      packaging on tobacco use uptake, cessation and reduction. SEARCH METHODS: We
      searched MEDLINE, Embase, PsycINFO and six other databases from 1980 to January
      2016. We checked bibliographies and contacted study authors to identify
      additional peer-reviewed studies. SELECTION CRITERIA: Primary outcomes included
      changes in tobacco use prevalence incorporating tobacco use uptake, cessation,
      consumption and relapse prevention. Secondary outcomes covered intermediate
      outcomes that can be measured and are relevant to tobacco use uptake, cessation
      or reduction. We considered multiple study designs: randomised controlled trials,
      quasi-experimental and experimental studies, observational cross-sectional and
      cohort studies. The review focused on all populations and people of any age; to
      be included, studies had to be published in peer-reviewed journals. We examined
      studies that assessed the impact of changes in tobacco packaging such as colour,
      design, size and type of health warnings on the packs in relation to branded
      packaging. In experiments, the control condition was branded tobacco packaging
      but could include variations of standardised packaging. DATA COLLECTION AND
      ANALYSIS: Screening and data extraction followed standard Cochrane methods. We
      used different 'Risk of bias' domains for different study types. We have
      summarised findings narratively. MAIN RESULTS: Fifty-one studies met our
      inclusion criteria, involving approximately 800,000 participants. The studies
      included were diverse, including observational studies, between- and within
      participant experimental studies, cohort and cross-sectional studies, and time
      series analyses. Few studies assessed behavioural outcomes in youth and non
      smokers. Five studies assessed the primary outcomes: one observational study
      assessed smoking prevalence among 700,000 participants until one year after
      standardised packaging in Australia; four studies assessed consumption in 9394
      participants, including a series of Australian national cross-sectional surveys
      of 8811 current smokers, in addition to three smaller studies. No studies
      assessed uptake, cessation, or relapse prevention. Two studies assessed quit
      attempts. Twenty studies examined other behavioural outcomes and 45 studies
      examined non-behavioural outcomes (e.g. appeal, perceptions of harm). In line
      with the challenges inherent in evaluating standardised tobacco packaging, a
      number of methodological imitations were apparent in the included studies and
      overall we judged most studies to be at high or unclear risk of bias in at least
      one domain. The one included study assessing the impact of standardised tobacco
      packaging on smoking prevalence in Australia found a 3.7% reduction in odds when
      comparing before to after the packaging change, or a 0.5 percentage point drop in
      smoking prevalence, when adjusting for confounders. Confidence in this finding is
      limited, due to the nature of the evidence available, and is therefore rated low
      by GRADE standards. Findings were mixed amongst the four studies assessing
      consumption, with some studies finding no difference and some studies finding
      evidence of a decrease; certainty in this outcome was rated very low by GRADE
      standards due to the limitations in study design. One national study of
      Australian adult smoker cohorts (5441 participants) found that quit attempts
      increased from 20.2% prior to the introduction of standardised packaging to 26.6%
      one year post-implementation. A second study of calls to quitlines provides
      indirect support for this finding, with a 78% increase observed in the number of
      calls after the implementation of standardised packaging. Here again, certainty
      is low. Studies of other behavioural outcomes found evidence of increased
      avoidance behaviours when using standardised packs, reduced demand for
      standardised packs and reduced craving. Evidence from studies measuring eye
      tracking showed increased visual attention to health warnings on standardised
      compared to branded packs. Corroborative evidence for the latter finding came
      from studies assessing non-behavioural outcomes, which in general found greater
      warning salience when viewing standardised, than branded packs. There was mixed
      evidence for quitting cognitions, whereas findings with youth generally pointed
      towards standardised packs being less likely to motivate smoking initiation than
      branded packs. We found the most consistent evidence for appeal, with
      standardised packs rating lower than branded packs. Tobacco in standardised packs
      was also generally perceived as worse-tasting and lower quality than tobacco in
      branded packs. Standardised packaging also appeared to reduce misperceptions that
      some cigarettes are less harmful than others, but only when dark colours were
      used for the uniform colour of the pack. AUTHORS' CONCLUSIONS: The available
      evidence suggests that standardised packaging may reduce smoking prevalence. Only
      one country had implemented standardised packaging at the time of this review, so
      evidence comes from one large observational study that provides evidence for this
      effect. A reduction in smoking behaviour is supported by routinely collected data
      by the Australian government. Data on the effects of standardised packaging on
      non-behavioural outcomes (e.g. appeal) are clearer and provide plausible
      mechanisms of effect consistent with the observed decline in prevalence. As
      standardised packaging is implemented in different countries, research programmes
      should be initiated to capture long term effects on tobacco use prevalence,
      behaviour, and uptake. We did not find any evidence suggesting standardised
      packaging may increase tobacco use.

PMID- 28447364
TI  - The jasmonic acid-signalling and abscisic acid-signalling pathways cross talk
      during one, but not repeated, dehydration stress: a non-specific 'panicky' or a
      meaningful response?
AB  - Experiencing diverse and recurring biotic and abiotic stresses throughout life,
      plants have evolved mechanisms to respond, survive and, eventually, adapt to
      changing habitats. The initial response to drought involves a large number of
      genes that are involved also in response to other stresses. According to current
      models, this initial response is non-specific, becoming stress-specific only at
      later time points. The question, then, is whether non-specific activation of
      various stress-signalling systems leading to the expression of numerous stress
      regulated genes is a false-alarm (panicky) response or whether it has
      biologically relevant consequences for the plant. Here, it is argued that the
      initial activation of genes associated other stresses reflects an important event
      during which stress-specific mechanisms are generated to prevent subsequent
      activation of non-drought signalling pathways. How plants discriminate between a
      first and a repeated dehydration stress and how repression of non-drought
      specific genes is achieved will be discussed on the example of jasmonic acid
      associated Arabidopsis genes activated by a first, but not subsequent,
      dehydration stresses. Revealing how expression of various biotic/abiotic stress
      responding genes is prevented under recurring drought spells may be critical for
      our understanding of how plants respond to dynamically changing environments.

PMID- 28447365
TI  - Boosted food web productivity through ocean acidification collapses under
      warming.
AB  - Future climate is forecast to drive bottom-up (resource driven) and top-down
      (consumer driven) change to food web dynamics and community structure. Yet, our
      predictive understanding of these changes is hampered by an over-reliance on
      simplified laboratory systems centred on single trophic levels. Using a large
      mesocosm experiment, we reveal how future ocean acidification and warming modify
      trophic linkages across a three-level food web: that is, primary (algae),
      secondary (herbivorous invertebrates) and tertiary (predatory fish) producers.
      Both elevated CO2 and elevated temperature boosted primary production. Under
      elevated CO2 , the enhanced bottom-up forcing propagated through all trophic
      levels. Elevated temperature, however, negated the benefits of elevated CO2 by
      stalling secondary production. This imbalance caused secondary producer
      populations to decline as elevated temperature drove predators to consume their
      prey more rapidly in the face of higher metabolic demand. Our findings
      demonstrate how anthropogenic CO2 can function as a resource that boosts
      productivity throughout food webs, and how warming can reverse this effect by
      acting as a stressor to trophic interactions. Understanding the shifting balance
      between the propagation of resource enrichment and its consumption across trophic
      levels provides a predictive understanding of future dynamics of stability and
      collapse in food webs and fisheries production.

PMID- 28447366
TI  - Effects of dietary lysine levels on the concentrations of selected nutrient
      metabolites in blood plasma of late-stage finishing pigs.
AB  - Lysine is the first-limiting amino acid (AA) in typical swine diets and plays
      very important roles in promoting growth performance of pigs. This research was
      conducted to study the effects of dietary lysine on blood plasma concentrations
      of protein, carbohydrate, and lipid metabolites of pigs. Eighteen crossbred
      finishing pigs (nine barrows and nine gilts; initial BW 92.3 +/- 6.9 kg) were
      individually penned in an environment controlled barn. Pigs were assigned to
      three dietary treatments according to a randomized complete block design with
      gender as block and pig as experimental unit (6 pigs/treatment). Three corn and
      soybean meal-based diets were formulated to contain total lysine at 0.43%, 0.71%,
      and 0.98% (as-fed basis) for Diets I (lysine deficient), II (lysine adequate),
      and III (lysine excess) respectively. After 4 weeks on trial, jugular vein blood
      was collected and plasma was separated. The plasma concentrations of total
      protein, albumin, urea nitrogen (UN), triglyceride, total cholesterol, and
      glucose were determined using an ACE Clinical Chemistry System (Alfa Wassermann,
      Inc., West Caldwell, NJ, USA). Data were analysed using the GLM Procedure with
      PDIFF (adjust = T) option of SAS. No differences (p > 0.10) were found between
      barrows and gilts for any of the metabolites measured. While there were no
      differences (p > 0.10) between pigs fed Diets II and III in plasma concentrations
      of UN, albumin, and total cholesterol, the concentration of albumin in these pigs
      was higher (p < .05) than that of pigs fed Diet I, and the concentrations of UN
      and total cholesterol in these pigs were lower (p < .05) than that of pigs fed
      Diet I. There were no differences (p > 0.10) among the three dietary treatments
      in plasma concentrations of total protein, triglycerides, and glucose. These
      findings indicated that the plasma metabolite profile can be affected by changing
      dietary lysine content only. Thorough understanding how the plasma metabolite
      profile is alternated by dietary lysine will facilitate nutrient management for
      more sustainable swine production.

PMID- 28447367
TI  - Sex Hormones Function as Sex Attractant Pheromones in House Mice and Brown Rats.
AB  - Sex hormones of mammals control the expression of sexual characteristics and
      bodily functions. The male hormone testosterone and the female hormones
      progesterone and estradiol are known to occur in urine markings of mice. Here, we
      show that all three hormones are also present in urine of brown rats, and that
      they are effective sexual communication signals (pheromones) that elicit
      attraction behavior of prospective mates in both brown rats and house mice. When
      added as lures to trap boxes in field experiments, synthetic testosterone, for
      example, increased captures of adult female mice 15-fold, and a blend of
      progesterone and estradiol increased captures of male mice eightfold and male
      rats 13-fold. Remarkably, these hormones increased captures even though the food-
      and pheromone-based baits to which they were added had previously been shown to
      be superior to current commercial rodent attractants. We predict that these sex
      hormones will function as sex attractant pheromones in diverse taxa.

PMID- 28447368
TI  - Optimization of Aqueous Extraction and Biological Activity of Harpagophytum
      procumbens Root on Ex Vivo Rat Colon Inflammatory Model.
AB  - Harpagophytum procumbens has a long story of use for the treatment of
      inflammatory diseases. Considering both the antiinflammatory effects of H.
      procumbens in multiple tissues and the stability of harpagoside in artificial
      intestinal fluid, the aim of the present study was to explore the possible
      protective role of a microwave-assisted aqueous Harpagophytum extract (1-1000
      MUg/mL) on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell
      lines, and isolated rat colon specimens challenged with lipopolysaccharide (LPS),
      a validated ex vivo model of acute ulcerative colitis. In this context, we
      evaluated the effects on C2C12 and HCT116 viability, and on LPS-induced
      production of serotonin (5-HT), tumor necrosis factor (TNF)-alpha, prostaglandin
      (PG)E2 and 8-iso-prostaglandin (8-iso-PG)F2alpha . Harpagophytum extract was well
      tolerated by C2C12 cells, while reduced HCT116 colon cancer cell viability. On
      the other hand, Harpagophytum extract reduced H2 O2 -induced (1 mM) reactive
      oxygen species (ROS) production, in both cell lines, and inhibited LPS-induced
      colon production of PGE2 , 8-iso-PGF2alpha , 5-HT and TNFalpha. Concluding, we
      demonstrated the efficacy of a microwave-assisted Harpagophytum aqueous extract
      in modulating the inflammatory, oxidative stress and immune response in an
      experimental model of inflammatory bowel diseases (IBD), thus suggesting a
      rational use of Harpagophytum in the management and prevention of ulcerative
      colitis in humans. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28447369
TI  - Analyzing Reaction Rates with the Distortion/Interaction-Activation Strain Model.
AB  - The activation strain or distortion/interaction model is a tool to analyze
      activation barriers that determine reaction rates. For bimolecular reactions, the
      activation energies are the sum of the energies to distort the reactants into
      geometries they have in transition states plus the interaction energies between
      the two distorted molecules. The energy required to distort the molecules is
      called the activation strain or distortion energy. This energy is the principal
      contributor to the activation barrier. The transition state occurs when this
      activation strain is overcome by the stabilizing interaction energy. Following
      the changes in these energies along the reaction coordinate gives insights into
      the factors controlling reactivity. This model has been applied to reactions of
      all types in both organic and inorganic chemistry, including substitutions and
      eliminations, cycloadditions, and several types of organometallic reactions.

PMID- 28447370
TI  - Vulnerability to forest loss through altered postfire recovery dynamics in a
      warming climate in the Klamath Mountains.
AB  - In the context of ongoing climatic warming, certain landscapes could be near a
      tipping point where relatively small changes to their fire regimes or their
      postfire forest recovery dynamics could bring about extensive forest loss, with
      associated effects on biodiversity and carbon-cycle feedbacks to climate change.
      Such concerns are particularly valid in the Klamath Region of northern California
      and southwestern Oregon, where severe fire initially converts montane conifer
      forests to systems dominated by broadleaf trees and shrubs. Conifers eventually
      overtop the competing vegetation, but until they do, these systems could be
      perpetuated by a cycle of reburning. To assess the vulnerability of conifer
      forests to increased fire activity and altered forest recovery dynamics in a
      warmer, drier climate, we characterized vegetation dynamics following severe fire
      in nine fire years over the last three decades across the climatic aridity
      gradient of montane conifer forests. Postfire conifer recruitment was limited to
      a narrow window, with 89% of recruitment in the first 4 years, and height growth
      tended to decrease as the lag between the fire year and the recruitment year
      increased. Growth reductions at longer lags were more pronounced at drier sites,
      where conifers comprised a smaller portion of live woody biomass. An interaction
      between seed-source availability and climatic aridity drove substantial variation
      in the density of regenerating conifers. With increasing climatic water deficit,
      higher propagule pressure (i.e., smaller patch sizes for high-severity fire) was
      needed to support a given conifer seedling density, which implies that projected
      future increases in aridity could limit postfire regeneration across a growing
      portion of the landscape. Under a more severe prospective warming scenario, by
      the end of the century more than half of the area currently capable of supporting
      montane conifer forest could become subject to minimal conifer regeneration in
      even moderate-sized (10s of ha) high-severity patches.

PMID- 28447372
TI  - Rapid thermal adaptation in photosymbionts of reef-building corals.
AB  - Climate warming is occurring at a rate not experienced by life on Earth for 10 s
      of millions of years, and it is unknown whether the coral-dinoflagellate
      (Symbiodinium spp.) symbiosis can evolve fast enough to ensure coral reef
      persistence. Coral thermal tolerance is partly dependent on the Symbiodinium
      hosted. Therefore, directed laboratory evolution in Symbiodinium has been
      proposed as a strategy to enhance coral holobiont thermal tolerance. Using a
      reciprocal transplant design, we show that the upper temperature tolerance and
      temperature tolerance range of Symbiodinium C1 increased after ~80 asexual
      generations (2.5 years) of laboratory thermal selection. Relative to wild-type
      cells, selected cells showed superior photophysiological performance and growth
      rate at 31 degrees C in vitro, and performed no worse at 27 degrees C; they also
      had lower levels of extracellular reactive oxygen species (exROS). In contrast,
      wild-type cells were unable to photosynthesise or grow at 31 degrees C and
      produced up to 17 times more exROS. In symbiosis, the increased thermal tolerance
      acquired ex hospite was less apparent. In recruits of two of three species
      tested, those harbouring selected cells showed no difference in growth between
      the 27 and 31 degrees C treatments, and a trend of positive growth at both
      temperatures. Recruits that were inoculated with wild-type cells, however, showed
      a significant difference in growth rates between the 27 and 31 degrees C
      treatments, with a negative growth trend at 31 degrees C. There were no
      significant differences in the rate and severity of bleaching in coral recruits
      harbouring wild-type or selected cells. Our findings highlight the need for
      additional Symbiodinium genotypes to be tested with this assisted evolution
      approach. Deciphering the genetic basis of enhanced thermal tolerance in
      Symbiodinium and the cause behind its limited transference to the coral holobiont
      in this genotype of Symbiodinium C1 are important next steps for developing
      methods that aim to increase coral bleaching tolerance.

PMID- 28447373
TI  - Avoiding a crisis of motivation for ocean management under global environmental
      change.
AB  - Climate change and ocean acidification are altering marine ecosystems and, from a
      human perspective, creating both winners and losers. Human responses to these
      changes are complex, but may result in reduced government investments in
      regulation, resource management, monitoring and enforcement. Moreover, a lack of
      peoples' experience of climate change may drive some towards attributing the
      symptoms of climate change to more familiar causes such as management failure.
      Taken together, we anticipate that management could become weaker and less
      effective as climate change continues. Using diverse case studies, including the
      decline of coral reefs, coastal defences from flooding, shifting fish stocks and
      the emergence of new shipping opportunities in the Arctic, we argue that human
      interests are better served by increased investments in resource management. But
      greater government investment in management does not simply mean more of
      "business-as-usual." Management needs to become more flexible, better at
      anticipating and responding to surprise, and able to facilitate change where it
      is desirable. A range of technological, economic, communication and governance
      solutions exists to help transform management. While not all have been tested,
      judicious application of the most appropriate solutions should help humanity
      adapt to novel circumstances and seek opportunity where possible.

PMID- 28447371
TI  - Cooperation in microbial communities and their biotechnological applications.
AB  - Microbial communities are increasingly utilized in biotechnology. Efficiency and
      productivity in many of these applications depends on the presence of cooperative
      interactions between members of the community. Two key processes underlying these
      interactions are the production of public goods and metabolic cross-feeding,
      which can be understood in the general framework of ecological and evolutionary
      (eco-evo) dynamics. In this review, we illustrate the relevance of cooperative
      interactions in microbial biotechnological processes, discuss their mechanistic
      origins and analyse their evolutionary resilience. Cooperative behaviours can be
      damaged by the emergence of 'cheating' cells that benefit from the cooperative
      interactions but do not contribute to them. Despite this, cooperative
      interactions can be stabilized by spatial segregation, by the presence of
      feedbacks between the evolutionary dynamics and the ecology of the community, by
      the role of regulatory systems coupled to the environmental conditions and by the
      action of horizontal gene transfer. Cooperative interactions enrich microbial
      communities with a higher degree of robustness against environmental stress and
      can facilitate the evolution of more complex traits. Therefore, the evolutionary
      resilience of microbial communities and their ability to constraint detrimental
      mutants should be considered to design robust biotechnological applications.

PMID- 28447374
TI  - Effect of feeding a high-carbohydrate or a high-fat diet on subsequent food
      intake and blood concentration of satiety-related hormones in dogs.
AB  - Although studies in rodents and humans have evidenced a weaker effect of fat in
      comparison to carbohydrates on the suppression of food intake, very few studies
      have been carried out in this field in dogs. This study investigates the effects
      of a high-carbohydrate (HC) and a high-fat (HF) diets on subsequent food intake
      and blood satiety-related hormones in dogs. Diets differed mainly in their starch
      (442 vs. 271 g/kg dry matter) and fat (99.3 vs. 214 g/kg dry matter) contents.
      Twelve Beagle dogs received the experimental diets at maintenance energy
      requirements in two experimental periods, following a cross-over arrangement. In
      week 7 of each period, blood concentrations of active ghrelin, glucagon-like
      peptide (GLP-1), peptide YY, insulin, and glucose were determined before and at
      30, 60, 120, 180, and 360 min post-feeding. The following week, intake of a
      challenge food offered 180 min after the HC and HF diets was recorded over two
      days. In comparison to the dogs on the HC diet, those on the HF diet had a higher
      basal concentration of GLP-1 (p = .010) and a higher total area under the curve
      over 180 min post-prandial (tAUC0-180 ) (p = .031). Dogs on the HC diet showed a
      higher elevation of ghrelin at 180 min (p = .033) and of insulin at 360 min (p =
      .041), although ghrelin and insulin tAUC0-180 did not differ between the two
      diets (p ? .10). Diet had no effect on challenge food intake (p ? .10), which
      correlated with the tAUC0-180 of ghrelin (r = .514, p = .010), insulin (r = 
      .595, p = .002), and glucose (r = -.516, p = .010). Feeding a diet high in
      carbohydrate or fat at these inclusion levels does not affect the feeding
      response at 180 min post-prandial, suggesting a similar short-term satiating
      capacity.

PMID- 28447375
TI  - Clostridium difficile: A bad bug goes into defensive mode.

PMID- 28447376
TI  - Reduced fasting periods increase intestinal permeability in chickens.
AB  - Fasting of up to 24 hr has been shown to increase intestinal permeability (IP) in
      chickens. The aim of this study was to determine whether fasting duration of 4.5
      and 9 hr increased IP and whether l-glutamine (a non-essential amino acid)
      supplementation before fasting provided some protection of barrier function as
      shown in other species. Ross 308 male broilers (n = 96) were fed either a control
      diet or the same diet supplemented with 1% glutamine from d0 to d38 post-hatch.
      On d37, the birds were assigned to single-bird metabolism cages and were fasted
      for either 0, 4.5, 9 or 19.5 hr. This study design was 2 * 4 factorial with two
      levels of glutamine and four levels of fasting. Birds in the 0-hr fasting group
      had free access to feed. All birds had ad libitum access to water. To measure IP
      on day 38, following their respective fasting periods, birds were administered
      two separate oral gavages of fluorescein isothiocyanate dextran (FITC-d) followed
      by lactulose, mannitol and rhamnose (LMR) sugars, 60 min apart. Whole blood was
      collected from the jugular vein 90 min post-LMR sugar gavage. FITC-d and L/M/R
      ratios were measured by spectrophotometry and high-performance ionic
      chromatography respectively. Lipopolysaccharide (LPS) endotoxins in plasma of the
      birds fed the control diet were also measured using chicken-specific LPS antibody
      ELISA. Serum FITC-d and plasma L/M and L/R ratios for 4.5, 9 and 19.5 hr were
      significantly (p < .05) higher compared to the non-fasting group. However, IP was
      not different in the glutamine-supplemented group (p > .05) compared to the
      control group. LPS concentrations measured by the ELISA were below the detectable
      range. We conclude that fasting periods of 4.5 and 9 hr increased IP compared to
      non-fasted birds and dietary glutamine supplementation did not ameliorate changes
      in IP.

PMID- 28447377
TI  - Lupus miliaris disseminatus faciei: A resistant case with response to
      cyclosporine.
AB  - Lupus miliaris disseminatus faciei (LMDF) is a chronic, inflammatory dermatosis
      of unknown etiology, characterized by multiple, monomorphic, symmetrical, reddish
      brown papules over forehead, cheeks, and eyelids. Histopathology shows
      perifollicular epitheloid cell granuloma. Though numerous therapies, ranging from
      cyclines, macrolides, dapsone tranilast, isotretinoin, steroids, and tacrolimus
      have been tried, the results are inconsistent, except with systemic steroids. One
      approach is to administer therapies based on the histological findings and the
      corresponding mode of action of drugs, thus antibiotics and dapsone are effective
      in the early inflammatory stage while clofazamine can be used in the
      granulomatous stage of the disease. A case of LMDF, recalcitrant to multiple
      systemic therapies, who responded dramatically to cyclosporine (50 mg twice
      daily), which probably was due to the specific effect on TH 1 cell response which
      mediates cell mediated immunity responsible for granulomatous changes on
      histology has been reported. This case highlights that LMDF is an independent
      granulomatous entity (not a variant of rosacea or tuberculosis).

PMID- 28447378
TI  - Soil aggregation and associated microbial communities modify the impact of
      agricultural management on carbon content.
AB  - Soil carbon (C) stabilisation is known to depend in part on its distribution in
      structural aggregates, and upon soil microbial activity within the aggregates.
      However, the mechanisms and relative contributions of different microbial groups
      to C turnover in different aggregates under various management practices remain
      unclear. The aim of this study was to determine the role of soil aggregation and
      their associated microbial communities in driving the responses of soil organic
      matter (SOM) to multiple management practices. Our results demonstrate that
      higher amounts of C inputs coupled with greater soil aggregation in residue
      retention management practices has positive effects on soil C content. Our
      results provide evidence that different aggregate size classes support distinct
      microbial habitats which supports the colonisation of different microbial
      communities. Most importantly our results indicate that the effects of management
      practices on soil C is modulated by soil aggregate sizes and their associated
      microbial community and are more pronounced in macro-aggregate compared with
      micro-aggregate sizes. Based on our findings we recommend that differential
      response of management practices and microbial control on the C turnover in macro
      aggregates and micro-aggregate should be explicitly considered when accounting
      for management impacts on soil C turnover.

PMID- 28447379
TI  - Response to: Toriello et al., "Update on the Toriello-Carey Syndrome." Further
      delineation of a young woman with deletion 1q42.12-q42.2.

PMID- 28447380
TI  - LncRNA-H19 Modulates Wnt/beta-catenin Signaling by Targeting Dkk4 in Hindlimb
      Unloaded Rat.
AB  - OBJECTIVE: To investigate the biological functions of long noncoding RNA-H19
      (H19) in the pathogenesis of disuse osteoporosis (DOP). METHODS: Fifty-four male
      Sprague Dawley (SD) rats were randomly divided into three groups: baseline
      control (BC, 6), age-matched control (AC, 24), and hindlimb unloading (HLU, 24).
      The rats in the BC group were sacrificed at the beginning of the experiment,
      while the AC and HLU rats were sacrificed at different times (7, 14, 21 and 28
      days after HLU). The DOP model was verified by micro-CT scan, and quantitative
      real-time polymerase chain reaction (qRT-PCR) was used to quantify the expression
      of osteogenic genes (OPG, RunX2 and OPG). Gene sequencing and bioinformatic
      analysis were performed to find H19 target genes and the associated signaling
      pathway, which were first verified on tissue samples. Further verification was
      performed by knocking down the H19 and related gene in rat osteoblast cell line
      (UMR106 cell). Then, the changes of associated signaling pathway and osteogenic
      function were examined to confirm the prediction of the bioinformatic analysis.
      RESULTS: Micro-CT scans and quantitative real-time polymerase chain reaction (qRT
      PCR) tests showed progressively deteriorated trabecular bone and decreased level
      of osteogenic genes in the metaphysis of distal femur during HLU, indicating the
      successful establishment of a DOP model. According to RNA sequencing, 1351 mRNA
      and 464 lncRNA were abnormally expressed in response to mechanical unloading, in
      which the H19 decreased 2.86 fold in HLU rats. There were 1426 mRNA predicted to
      be the target genes of H19, and KEGG pathway analysis suggested that Wnt
      signaling pathway (Wnt signaling) was the top pathway responsible for these
      target genes. In the Wnt-associated genes targeted by H19, 11 were differentially
      expressed between HLU and AC rats, among which Dkk4 increased 2.44 fold in HLU
      rats when compared to normal controls. These results of sequencing and
      bioinformatic analysis were confirmed by the low expression of H19,
      overexpression of Dkk4 and inhibited Wnt signaling observed in DOP rats.
      Subsequent in vitro cell assay further demonstrated that knockdown of H19 led to
      upregulation of Dkk4, and inhibition of Wnt signaling and osteogenic function in
      UMR106 cell. These effects can be greatly reversed after application of knocking
      down Dkk4. CONCLUSION: Our findings demonstrated that low expression of H19,
      induced by mechanical unloading, leads to development of DOP through inhibition
      of Wnt signaling by promoting Dkk4 expression.

PMID- 28447381
TI  - Land-use influences phosphatase gene microdiversity in soils.
AB  - Phosphorus cycling exerts significant influence upon soil fertility and
      productivity - processes largely controlled by microbial activity. We adopted
      phenotypic and metagenomic approaches to investigate phosphatase genes within
      soils. Microbial communities in bare fallowed soil showed a marked capacity to
      utilise phytate for growth compared with arable or grassland soil communities.
      Bare fallowed soil contained lowest concentrations of orthophosphate. Analysis of
      metagenomes indicated phoA, phoD and phoX, and histidine acid and cysteine
      phytase genes were most abundant in grassland soil which contained the greatest
      amount of NaOH-EDTA extractable orthophosphate. Beta-propeller phytase genes were
      most abundant in bare fallowed soil. Phylogenetic analysis of metagenome
      sequences indicated the phenotypic shift observed in the capacity to mineralise
      phytate in bare fallow soil was accompanied by an increase in phoD, phoX and beta
      propeller phytase genes coding for exoenzymes. However, there was a remarkable
      degree of genetic similarity across the soils despite the differences in land
      use. Predicted extracellular ecotypes were distributed across a greater range of
      soil structure than predicted intracellular ecotypes, suggesting that microbial
      communities subject to the dual stresses of low nutrient availability and reduced
      access to organic material in bare fallowed soils rely upon the action of
      exoenzymes.

PMID- 28447382
TI  - Quantitative proteomic analysis of EZH2 inhibition in acute myeloid leukemia
      reveals the targets and pathways that precede the induction of cell death.
AB  - PURPOSE: Chromosomal translocation of the mixed lineage leukemia (MLL) locus
      generates fusion proteins that drive acute myeloid leukemia (AML) resulting in
      atypical histone methyltransferase activity and alterations in the epigenetic
      regulation of gene expression. Targeting histone regulators, such as Enhancer of
      Zeste Homologue 2 (EZH2), has shown promise in AML. Profiling differential
      protein expression following inhibition of epigenetic regulators in AML may help
      to identify novel targets for therapeutics. EXPERIMENTAL DESIGN: Murine models of
      AML combined with quantitative SILAC analysis were used to identify
      differentially expressed proteins following inhibition of EZH2 activity using 3
      Deazaneplanocin A (DZnep). Western blotting and flow cytometry were used to
      validate a subset of differentially expressed proteins. Gene set analysis was
      used to determine changes to reported EZH2 target genes. RESULTS: Our
      quantitative proteomic analysis and subsequent validation of protein changes
      identified that epigenetic therapy leads to cell death preceded by the induction
      of differentiation with concurrent p53 up-regulation and cell cycle arrest. Gene
      set analysis revealed a specific subset of EZH2 target genes that were regulated
      by DZnep in AML. CONCLUSION AND CLINICAL RELEVANCE: These discoveries highlight
      how this new class of drugs affects AML cell biology and cell survival, and may
      help identify novel targets and strategies to increase treatment efficacy.

PMID- 28447384
TI  - Alpha-lipoic acid: An inimitable feed supplement for poultry nutrition.
AB  - Alpha-lipoic acid (ALA) is a multifunction antioxidant that is produced in small
      amount by cells as well as its dietary provision facilitates fatty acid
      mobilization, energy expenditure as well as can scavenge free radicals in poultry
      birds. It exists in oxidized as well as reduced form, characterized by growth
      promoting, anti-inflammatory, antioxidative, immunostimulatory, and
      hypocholesterolemic properties when fed as dietary supplement to farm animals
      particularly chicken birds. Recently, several studies reported that dietary
      supplementation of ALA can influence growth performance indicators,
      immunological, biochemical characteristics, lipid metabolism, and oxidative
      stress as well as increase antioxidant potential and storability of poultry meat
      and meat products. Accordingly, this paper adds the reviews and discusses the
      outcomes of studies documenting the effect of lipoic acid dietary fortification
      on growth performance, biochemical, and immunological characteristics as well as
      the effects on lipid peroxidation of fresh meat and meat-based products.
      Furthermore, this paper also describes the possibilities of utilization of ALA as
      a feed additive in poultry nutrition to improve the growth performance of poultry
      as well as meat quality of resultant chicken birds.

PMID- 28447383
TI  - Manganese transport is essential for N2 -fixation by Rhizobium leguminosarum in
      bacteroids from galegoid but not phaseoloid nodules.
AB  - Rhizobium leguminosarum has two high-affinity Mn2+ transport systems encoded by
      sitABCD and mntH. In symbiosis, sitABCD and mntH were expressed throughout
      nodules and also strongly induced in Mn2+ -limited cultures of free-living cells.
      Growth of a sitA mntH double mutant was severely reduced under Mn2+ limitation
      and sitA and mntH single mutants were more sensitive to oxidative stress. The
      double sitA mntH mutant of R. leguminosarum was unable to fix nitrogen (Fix- )
      with legumes belonging to the galegoid clade (Pisum sativum, Vicia faba and Vicia
      hirsuta). The presence of infection thread-like structures and sparsely-packed
      plant cells in nodules suggest that bacteroid development was blocked, either at
      a late stage of infection thread progression or during bacteroid-release. In
      contrast, a double sitA mntH mutant was Fix+ on common bean (Phaseoli vulgaris),
      a member of the phaseoloid clade of legumes, indicating a host-specific symbiotic
      requirement for Mn2+ transport.

PMID- 28447385
TI  - Ultrasound enhances calcium absorption of jujube fruit by regulating the cellular
      calcium distribution and metabolism of cell wall polysaccharides.
AB  - BACKGROUND: Ultrasound has been applied in fruit pre-washing processes. However,
      it is not sufficient to protect fruit from pathogenic infection throughout the
      entire storage period, and sometimes ultrasound causes tissue damage. The goal of
      this study was to investigate the effects of calcium chloride (CaCl2 , 10 g L-1 )
      and ultrasound (350 W at 40 kHz), separately and in combination, on jujube fruit
      quality, antioxidant status, tissue Ca2+ content and distribution along with cell
      wall metabolism at 20  degrees C for 6 days. RESULTS: All three treatments
      significantly maintained fruit firmness and peel color, reduced respiration rate,
      decay incidence, superoxide anion, hydrogen peroxide and malondialdehyde and
      preserved higher enzymatic (superoxide dismutase, catalase and peroxidase) and
      non-enzymatic (ascorbic acid and glutathione) antioxidants compared with the
      control. Moreover, the combined treatment was more effective in increasing tissue
      Ca2+ content and distribution, inhibiting the generation of water-soluble and
      CDTA-soluble pectin fractions, delaying the solubilization of Na2 CO3 -soluble
      pectin and having lower activities of cell wall-modifying enzymes
      (polygalacturonase and pectate lyase) during storage. CONCLUSION: These results
      demonstrated that the combination of CaCl2 and ultrasound has potential
      commercial application to extend the shelf life of jujube fruit by facilitating
      Ca2+ absorption and stabilizing the cell wall structure. (c) 2017 Society of
      Chemical Industry.

PMID- 28447386
TI  - Unravelling the pleiotropic role of the MceG ATPase in Mycobacterium smegmatis.
AB  - The Mce systems are complex ABC transporters that are encoded by different
      numbers of homologous operons in Actinobacteria. While the four Mce systems of
      Mycobacterium tuberculosis are all energized by a single ATPase, MceG, each
      system appears to import different fatty acids or sterols. To explore if this
      behaviour can be extended to saprophytic mycobacteria, whose more complex genomes
      encode more Mce systems, we have identified and characterized the MceG orthologue
      of Mycobacterium smegmatis. This bacterium relies on MceG to energize its six Mce
      systems that contribute to a variety of cellular functions including sterol
      uptake and cell envelope maintenance. In the absence of MceG, M. smegmatis was
      not able to utilize cholesterol or phytosterols as carbon sources implying that
      this ATPase is necessary to energize the Mce4-sterol transport system. Other
      phenotypic alterations observed in the DeltaMceG mutant, such as cell envelope
      modifications, suggest a pleiotropic functionality of the Mce systems that are
      particularly important for stress responses. Several DeltaMceG phenotypes were
      recapitulated in a strain lacking only the unique C-terminal region of MceG,
      suggesting an important functional or regulatory function for this domain.

PMID- 28447387
TI  - Who has 'Dibs!' on a dead rhinoceros beetle?

PMID- 28447388
TI  - Incidental learning in a multisensory environment across childhood.
AB  - Multisensory information has been shown to modulate attention in infants and
      facilitate learning in adults, by enhancing the amodal properties of a stimulus.
      However, it remains unclear whether this translates to learning in a multisensory
      environment across middle childhood, and particularly in the case of incidental
      learning. One hundred and eighty-one children aged between 6 and 10 years
      participated in this study using a novel Multisensory Attention Learning Task
      (MALT). Participants were asked to respond to the presence of a target stimulus
      whilst ignoring distractors. Correct target selection resulted in the movement of
      the target exemplar to either the upper left or right screen quadrant, according
      to category membership. Category membership was defined either by visual-only,
      auditory-only or multisensory information. As early as 6 years of age, children
      demonstrated greater performance on the incidental categorization task following
      exposure to multisensory audiovisual cues compared to unisensory information.
      These findings provide important insight into the use of multisensory information
      in learning, and particularly on incidental category learning. Implications for
      the deployment of multisensory learning tasks within education across development
      will be discussed.

PMID- 28447389
TI  - Outer membrane vesicles from Fibrobacter succinogenes S85 contain an array of
      carbohydrate-active enzymes with versatile polysaccharide-degrading capacity.
AB  - Fibrobacter succinogenes is an anaerobic bacterium naturally colonising the rumen
      and cecum of herbivores where it utilizes an enigmatic mechanism to deconstruct
      cellulose into cellobiose and glucose, which serve as carbon sources for growth.
      Here, we illustrate that outer membrane vesicles (OMVs) released by F.
      succinogenes are enriched with carbohydrate-active enzymes and that intact OMVs
      were able to depolymerize a broad range of linear and branched hemicelluloses and
      pectin, despite the inability of F. succinogenes to utilize non-cellulosic
      (pentose) sugars for growth. We hypothesize that the degradative versatility of
      F. succinogenes OMVs is used to prime hydrolysis by destabilising the tight
      networks of polysaccharides intertwining cellulose in the plant cell wall, thus
      increasing accessibility of the target substrate for the host cell. This is
      supported by observations that OMV-pretreatment of the natural complex substrate
      switchgrass increased the catalytic efficiency of a commercial cellulose
      degrading enzyme cocktail by 2.4-fold. We also show that the OMVs contain a
      putative multiprotein complex, including the fibro-slime protein previously found
      to be important in binding to crystalline cellulose. We hypothesize that this
      complex has a function in plant cell wall degradation, either by catalysing
      polysaccharide degradation itself, or by targeting the vesicles to plant biomass.

PMID- 28447390
TI  - High non-esterified fatty acid concentrations promote expression and secretion of
      fibroblast growth factor 21 in calf hepatocytes cultured in vitro.
AB  - Negative energy balance is considered as the pathological basis of energy
      metabolic disorders in periparturient dairy cows. Serum non-esterified fatty
      acids (NEFA) are one of the most important indicators of energy balance status.
      Fibroblast growth factor 21 (FGF21) has been identified as a hepatokine involved
      in regulation of metabolic adaptations, such as promoting hepatic lipid oxidation
      and ketogenesis, during energy deprivation. However, the direct effects of NEFA
      on FGF21 expression and secretion in bovine hepatocytes are not entirely clear.
      The objective of this study was to investigate the effects of different NEFA
      concentrations on FGF21 expression and secretion in calf hepatocytes cultured in
      vitro. NEFA were added to the culture solution at final concentrations of 0.6,
      1.2, 1.8 and 2.4 mmol/L. After 24 hr of continuous culture, FGF21 mRNA and
      protein expression levels in the hepatocytes were determined by real-time PCR and
      Western blot respectively. FGF21 secretion in the supernatant was determined by
      enzyme-linked immunosorbent assay (ELISA). The results showed that expression and
      secretion of FGF21 at 0.6 mmol/L NEFA-treated hepatocytes was higher than that of
      the control group (p < .05). The FGF21 expression and secretion were similar at
      1.2, 1.8 and 2.4 mmol/L NEFA-treated hepatocytes and significantly higher than
      those observed for controls (p < .01). These data suggest that high
      concentrations of NEFA significantly promote FGF21 expression and secretion in
      bovine hepatocytes. In particular, this promotion occurs in a dose-dependent
      manner and may be involved in the pathological processes of energy metabolism
      disorders of dairy cows in the peripartum period.

PMID- 28447392
TI  - Correction.

PMID- 28447391
TI  - Transcriptional response of Escherichia coli to ammonia and glucose fluctuations.
AB  - In large-scale production processes, metabolic control is typically achieved by
      limited supply of essential nutrients such as glucose or ammonia. With increasing
      bioreactor dimensions, microbial producers such as Escherichia coli are exposed
      to changing substrate availabilities due to limited mixing. In turn, cells sense
      and respond to these dynamic conditions leading to frequent activation of their
      regulatory programmes. Previously, we characterized short- and long-term
      strategies of cells to adapt to glucose fluctuations. Here, we focused on
      fluctuating ammonia supply while studying a continuously running two-compartment
      bioreactor system comprising a stirred tank reactor (STR) and a plug-flow reactor
      (PFR). The alarmone ppGpp rapidly accumulated in PFR, initiating considerable
      transcriptional responses after 70 s. About 400 genes were repeatedly switched
      on/off when E. coli returned to the STR. E. coli revealed highly diverging long
      term transcriptional responses in ammonia compared to glucose fluctuations. In
      contrast, the induction of stringent regulation was a common feature of both
      short-term responses. Cellular ATP demands for coping with fluctuating ammonia
      supply were found to increase maintenance by 15%. The identification of genes
      contributing to the increased ATP demand together with the elucidation of
      regulatory mechanisms may help to create robust cells and processes for large
      scale application.

PMID- 28447394
TI  - Estimation of maintenance energy requirements in German shepherd and Labrador
      retriever dogs in Bangalore, India.
AB  - Maintenance energy requirements (MERs) were calculated for 17 German shepherd and
      20 Labrador retriever adult dogs using an in-home prospective dietary trial. The
      dogs were fed the same dry pet food and body weight, food intake, body condition
      score and physical activity were monitored for 10 weeks. Labrador retrievers were
      significantly heavier and had higher body condition scores than German shepherd
      dogs, but there was no difference between males and females within each group.
      Body weights remained stable over the study period, with an average daily gain of
      9.1 g. Mean (SD) MER was 103.4 (16.3) kcal/kg BW0.75 , which was some 20% lower
      than that currently suggested for moderately active young adult dogs. Individual
      MER ranged from 66.8 to 141 kcal/kg BW0.75 . There were no significant
      differences in MER between the two breeds, or between males and females within
      and between the two breeds. There was a significant inverse relationship between
      MER and body condition score, reflecting the lower energy expenditure of adipose
      tissue. The lower MER of dogs in this study, relative to previous observations,
      may reflect climatic and environmental differences and highlight the necessity
      for accurate estimates of MER in relation to the production and feeding of pet
      foods.

PMID- 28447395
TI  - Land scale biogeography of arsenic biotransformation genes in estuarine wetland.
AB  - As an analogue of phosphorus, arsenic (As) has a biogeochemical cycle coupled
      closely with other key elements on the Earth, such as iron, sulfate and
      phosphate. It has been documented that microbial genes associated with As
      biotransformation are widely present in As-rich environments. Nonetheless, their
      presence in natural environment with low As levels remains unclear. To address
      this issue, we investigated the abundance levels and diversities of aioA, arrA,
      arsC and arsM genes in estuarine sediments at low As levels across Southeastern
      China to uncover biogeographic patterns at a large spatial scale. Unexpectedly,
      genes involved in As biotransformation were characterized by high abundance and
      diversity. The functional microbial communities showed a significant decrease in
      similarity along the geographic distance, with higher turnover rates than
      taxonomic microbial communities based on the similarities of 16S rRNA genes.
      Further investigation with niche-based models showed that deterministic processes
      played primary roles in shaping both functional and taxonomic microbial
      communities. Temperature, pH, total nitrogen concentration, carbon/nitrogen ratio
      and ferric iron concentration rather than As content in these sediments were
      significantly linked to functional microbial communities, while sediment
      temperature and pH were linked to taxonomic microbial communities. We proposed
      several possible mechanisms to explain these results.

PMID- 28447397
TI  - An LC-MS/MS method for determination of bioactive components of liquorice and
      Semen Strychni in rat plasma: Application to a pharmacokinetics study.
AB  - Semen Strychni is known for its treatment of rheumatic arthritis with a low
      therapeutic index. Liquorice contributes a lot in herb detoxification according
      to the traditional Chinese medicine theory. A simple, rapid, and sensitive liquid
      chromatography-mass spectrometric method (LC-MS) was developed and validated for
      simultaneous determination of main bioactive ingredients in liquorice and Semen
      Strychni in rat plasma. Using moclobemide and cyproterone acetate as the internal
      standards, the analytes were pretreated via protein precipitation with methanol.
      An Ultimate AQ-C18 column (3.0 MUm, 3.0 * 100 mm) was employed for
      chromatographic separation, combining with gradient elution. The mobile phase
      consisted of 0.07% formic acid and 0.12% ammonium acetate in aqueous phase (A)
      and acetonitrile in organic phase (B). The elution program was as follows: 0-0.5
      min, 20% B; 0.5-1 min, 20-60% B; 1-7 min, 60-85% B; and 7-7.5 min, returned to
      20% B, then continued to 12 min. Selected reaction monitoring was performed in
      both positive and negative ESI. Positive mode was adopted for detection of
      strychnine, brucine, and moclobemide, while negative mode was used for
      glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, isoliquiritigenin,
      liquiritin, and cyproterone acetate. The method was validated for specificity,
      linearity, matrix effect, recovery, precision, accuracy, and stability. The
      results show that this method is sensitive, accurate and robust for biological
      matrix analysis. Moreover, the proposed method was applied to a pharmacokinetic
      study in Sprague-Dawley rats for investigating the mechanism of which liquorice
      detoxifies Semen Strychni.

PMID- 28447396
TI  - Carbon nanotubes accelerate methane production in pure cultures of methanogens
      and in a syntrophic coculture.
AB  - Carbon materials have been reported to facilitate direct interspecies electron
      transfer (DIET) between bacteria and methanogens improving methane production in
      anaerobic processes. In this work, the effect of increasing concentrations of
      carbon nanotubes (CNT) on the activity of pure cultures of methanogens and on
      typical fatty acid-degrading syntrophic methanogenic coculture was evaluated. CNT
      affected methane production by methanogenic cultures, although acceleration was
      higher for hydrogenotrophic methanogens than for acetoclastic methanogens or
      syntrophic coculture. Interestingly, the initial methane production rate (IMPR)
      by Methanobacterium formicicum cultures increased 17 times with 5 g.L-1 CNT.
      Butyrate conversion to methane by Syntrophomonas wolfei and Methanospirillum
      hungatei was enhanced (~1.5 times) in the presence of CNT (5 g.L-1 ), but
      indications of DIET were not obtained. Increasing CNT concentrations resulted in
      more negative redox potentials in the anaerobic microcosms. Remarkably, without a
      reducing agent but in the presence of CNT, the IMPR was higher than in
      incubations with reducing agent. No growth was observed without reducing agent
      and without CNT. This finding is important to re-frame discussions and re
      interpret data on the role of conductive materials as mediators of DIET in
      anaerobic communities. It also opens new challenges to improve methane production
      in engineered methanogenic processes.

PMID- 28447398
TI  - A suite of essential biodiversity variables for detecting critical biodiversity
      change.
AB  - Key global indicators of biodiversity decline, such as the IUCN Red List Index
      and the Living Planet Index, have relatively long assessment intervals. This
      means they, due to their inherent structure, function as late-warning indicators
      that are retrospective, rather than prospective. These indicators are
      unquestionably important in providing information for biodiversity conservation,
      but the detection of early-warning signs of critical biodiversity change is also
      needed so that proactive management responses can be enacted promptly where
      required. Generally, biodiversity conservation has dealt poorly with the
      scattered distribution of necessary detailed information, and needs to find a
      solution to assemble, harmonize and standardize the data. The prospect of
      monitoring essential biodiversity variables (EBVs) has been suggested in response
      to this challenge. The concept has generated much attention, but the EBVs
      themselves are still in development due to the complexity of the task, the
      limited resources available, and a lack of long-term commitment to maintain EBV
      data sets. As a first step, the scientific community and the policy sphere should
      agree on a set of priority candidate EBVs to be developed within the coming years
      to advance both large-scale ecological research as well as global and regional
      biodiversity conservation. Critical ecological transitions are of high importance
      from both a scientific as well as from a conservation policy point of view, as
      they can lead to long-lasting biodiversity change with a high potential for
      deleterious effects on whole ecosystems and therefore also on human well-being.
      We evaluated candidate EBVs using six criteria: relevance, sensitivity to change,
      generalizability, scalability, feasibility, and data availability and provide a
      literature-based review for eight EBVs with high sensitivity to change. The
      proposed suite of EBVs comprises abundance, allelic diversity, body mass index,
      ecosystem heterogeneity, phenology, range dynamics, size at first reproduction,
      and survival rates. The eight candidate EBVs provide for the early detection of
      critical and potentially long-lasting biodiversity change and should be
      operationalized as a priority. Only with such an approach can science predict the
      future status of global biodiversity with high certainty and set up the
      appropriate conservation measures early and efficiently. Importantly, the
      selected EBVs would address a large range of conservation issues and contribute
      to a total of 15 of the 20 Aichi targets and are, hence, of high biological
      relevance.

PMID- 28447400
TI  - Genome-wide identification of pathogenicity, conidiation and colony sectorization
      genes in Metarhizium robertsii.
AB  - Metarhizium robertsii occupies a wide array of ecological niches and has diverse
      lifestyle options (saprophyte, insect pathogen and plant symbiont), that renders
      it an unusually effective model for studying genetic mechanisms for fungal
      adaptation. Here over 20,000 M. robertsii T-DNA mutants were screened in order to
      elucidate genetic mechanism by which M. robertsii replicates and persists in
      diverse niches. About 287 conidiation, colony sectorization or pathogenicity
      loci, many of which have not been reported in other fungi were identified. By
      analysing a series of conidial pigmentation mutants, a new fungal pigmentation
      gene cluster, which contains Mr-Pks1, Mr-EthD and Mlac1 was identified. A
      conserved conidiation regulatory pathway containing Mr-BrlA, Mr-AbaA and Mr-WetA
      regulates expression of these pigmentation genes. During conidiation Mr-BlrA up
      regulates Mr-AbaA, which in turn controls Mr-WetA. It was found that Hog1-MAPK
      regulates fungal conidiation by controlling the conidiation regulatory pathway,
      and that all three pigmentation genes exercise feedback regulation of
      conidiation. This work provided the foundation for deeper understanding of the
      genetic processes behind M. robertsii adaptive phenotypes, and advances our
      insights into conidiation and pigmentation in this fungus.

PMID- 28447399
TI  - Genome-wide association study of HIV-associated neurocognitive disorder (HAND): A
      CHARTER group study.
AB  - HIV-associated neurocognitive disorder (HAND) often complicates HIV infection
      despite combination antiretroviral therapy (ART) and may be influenced by host
      genomics. We performed a genome-wide association study (GWAS) of HAND in 1,050
      CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Study participants.
      All participants underwent standardized, comprehensive neurocognitive, and
      neuromedical assessments to determine if they had cognitive impairment as
      assessed by the Global Deficit Score (GDS), and individuals with comorbidities
      that could confound diagnosis of HAND were excluded. Neurocognitive outcomes
      included GDS-defined neurocognitive impairment (NCI; binary GDS, 366 cases with
      GDS >= 0.5 and 684 controls with GDS < 0.5, and GDS as a continuous variable) and
      Frascati HAND definitions that incorporate assessment of functional impairment by
      self-report and performance-based criteria. Genotype data were obtained using the
      Affymetrix Human SNP Array 6.0 platform. Multivariable logistic or linear
      regression-based association tests were performed for GDS-defined NCI and HAND.
      GWAS results did not reveal SNPs meeting the genome-wide significance threshold
      (5.0 * 10-8 ) for GDS-defined NCI or HAND. For binary GDS, the most significant
      SNPs were rs6542826 (P = 8.1 * 10-7 ) and rs11681615 (1.2 * 10-6 ), both located
      on chromosome 2 in SH3RF3. The most significant SNP for continuous GDS was
      rs11157436 (P = 1.3 * 10-7 ) on chromosome 14 in the T-cell-receptor alpha locus;
      three other SNPs in this gene were also associated with binary GDS (P <= 2.9 * 10
      6 ). This GWAS, conducted among ART-era participants from a single cohort with
      robust neurological phenotyping, suggests roles for several biologically
      plausible loci in HAND that deserve further exploration. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28447401
TI  - Valgus malalignment and prevalence of lateral compartmental radiographic knee
      osteoarthritis (OA): The Wuchuan OA study.
AB  - AIM: To evaluate whether knee alignment explains the higher prevalence of lateral
      compartment tibiofemoral radiographic osteoarthritis (TFROA) among rural Chinese
      compared with that among Whites. METHODS: The Wuchuan OA Study is a population
      based longitudinal study of risk factors for knee OA. At baseline 1030
      participants had home interviews, clinical examinations and weight-bearing
      posteroanterior semi-flexed radiographs of the tibiofemoral joints. Anatomic knee
      alignment was measured using an e-film workstation and divided into three
      categories: normal (182 degrees -184 degrees ), valgus (> 184 degrees ), and
      varus (< 182 degrees ) alignment. A knee was defined as having medial or lateral
      compartmental ROA if its Kellgren and Lawrence grade was >= 2 and joint space
      narrowing >= 1 in the medial or lateral compartment, respectively. We examined
      the association between knee alignment with prevalent medial or lateral knee ROA
      separately using multiple logistic regression. RESULTS: Among 1030 participants,
      the proportions of knees with normal, valgus and varus alignment were 29.9%,
      56.5% and 13.7%, respectively. The prevalence of medial and lateral ROA was 16.0%
      and 4.3%, respectively. Valgus alignment was associated with prevalence of
      lateral compartment ROA (odds ratio [OR] = 5.0, 95% CI: 2.4-10.5), while varus
      alignment was associated with medial compartment ROA (OR = 6.1, 95% CI: 4.4-8.6).
      The ratio of prevalence of lateral versus medial compartment TFROA was greater in
      Wuchuan than that in the Framingham OA Study and valgus malalignment was more
      common in Wuchuan than in the Rotterdam study. CONCLUSIONS: The prevalence of
      compartment-specific TFROA differs between rural Chinese and Whites. This
      difference is likely due to relatively high prevalence of valgus malalignment in
      rural Chinese compared with that in Whites.

PMID- 28447403
TI  - Management of Inherited Bleeding Disorders in Pregnancy: Green-top Guideline No.
      71 (joint with UKHCDO).

PMID- 28447402
TI  - Is extra-glandular organ damage in primary Sjogren's syndrome related to the
      presence of systemic auto-antibodies and/or hypergammaglobulinemia? A long-term
      cohort study with 110 patients from the Netherlands.
AB  - AIM: To test the hypothesis that systemic auto-antibodies or
      hypergammaglobulinemia are related to the prevalence of extra-glandular tissue
      organ damage (EGOD) in primary Sjogren's syndrome (SS). METHODS: A real practice
      based investigation of a relatively large (n = 110) Dutch cohort of primary SS
      patients systematically followed up in a large non-academic hospital. RESULTS:
      After a follow up of mean 8.2 years a significant correlation was found between
      disease duration and the prevalence of EGOD. We did not observe a relationship
      between the total number or type of systemic auto-antibodies or
      hypergammaglobulinemia and the total number of EGOD. However, there was a
      correlation between the prevalence of polyneuropathy (PNP) and antinuclear
      antibodies (ANA) as well as anti-Ro/SS-A positivity and there was an inverse
      relationship between the presence of anti-Ro/SS-A antibodies and primary biliary
      cirrhosis (PBC). All PBC cases were anti-Ro/SS-A and anti-La/SS-B negative but
      ANA positive. There was a trend for a higher occurrence of pleuro-pulmonary
      disease in the ANA negative cases. CONCLUSIONS: Although we did not find a
      relationship between the total number or type of systemic auto-antibodies and the
      total number of EGOD, there were correlations between specific systemic auto
      antibodies and specific types of EGOD. The presence of ANA and anti-Ro/SS-A was
      associated with the occurrence of PNP, as well as was the absence of anti-Ro/SS-A
      with PBC.

PMID- 28447404
TI  - Potential biomechanical roles of risk factors in the evolution of thrombus-laden
      abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysms (AAAs) typically harbour an intraluminal thrombus
      (ILT), yet most prior computational models neglect biochemomechanical effects of
      thrombus on lesion evolution. We recently proposed a growth and remodelling model
      of thrombus-laden AAAs that introduced a number of new constitutive relations and
      associated model parameters. Because values of several of these parameters have
      yet to be elucidated by clinical data and could vary significantly from patient
      to patient, the aim of this study was to investigate the possible extent to which
      these parameters influence AAA evolution. Given that some of these parameters
      model potential effects of factors that influence the risk of rupture, this study
      also provides insight into possible roles of common risk factors on the natural
      history of AAAs. Despite geometrical limitations of a cylindrical domain,
      findings support current thought that smoking, hypertension, and female sex
      likely increase the risk of rupture. Although thrombus thickness is not a
      reliable risk factor for rupture, the model suggests that the presence of ILT may
      have a destabilizing effect on AAA evolution, consistent with histological
      findings from human samples. Finally, simulations support two hypotheses that
      should be tested on patient-specific geometries in the future. First, ILT is a
      potential source of the staccato enlargement observed in many AAAs. Second, ILT
      can influence rupture risk, positively or negatively, via competing biomechanical
      (eg, stress shielding) and biochemical (ie, proteolytic) effects. Although
      further computational and experimental studies are needed, the present findings
      highlight the importance of considering ILT when predicting aneurysmal
      enlargement and rupture risk.

PMID- 28447405
TI  - High mortality from Guillain-Barre syndrome in Bangladesh.
AB  - Although Guillain-Barre syndrome (GBS) has higher incidence and poor outcome in
      Bangladesh, mortality from GBS in Bangladesh has never been explored before. We
      sought to explore the frequency, timing, and risk factors for deaths from GBS in
      Bangladesh. We conducted a prospective study on 407 GBS patients who were
      admitted to Dhaka Medical College Hospital, Dhaka, Bangladesh from 2010 to 2013.
      We compared deceased and alive patients to identify risk factors. Cox regression
      model was used to adjust for confounders. Of the 407 GBS patients, 50 (12%) died,
      with the median time interval between the onset of weakness and death of 18 days.
      Among the fatal cases, 24 (48%) were >=40 years, 36 (72%) had a Medical Research
      Council sum score <=20 at entry, 33 (66%) had a progressive phase <8 days, and 27
      (54%) required ventilation support. Ten patients (20%) died due to unavailability
      of ventilator. The strongest risk factor for deaths was lack of ventilator
      support when it was required (HR: 11.9; 95% confidence interval [CI]: 4.6-30.7).
      Other risk factors for death included age >=40 years (HR: 5.9; 95% CI: 2.1-16.7),
      mechanical ventilation (HR: 2.3; 95% CI: 1.02-5.2), longer progressive phase (>8
      days) (HR: 2.06; 95% CI: 1.1-3.8), autonomic dysfunction (HR: 1.9; 95% CI: 1.05
      3.6), and bulbar nerve involvement (HR: 5.4; 95% CI: 1.5-19.2). In Bangladesh,
      GBS is associated with higher mortality rates, which is related to lack of
      ventilator support, disease severity, longer progressive phase of the disease,
      autonomic dysfunction, and involvement of the bulbar nerves.

PMID- 28447407
TI  - Wiedemann-Rautenstrauch syndrome: A phenotype analysis.
AB  - Wiedemann-Rautenstrauch syndrome (WRS) is a neonatal progeroid disorder
      characterized by growth retardation, lipodystrophy, a distinctive face, and
      dental anomalies. Patients reported to date demonstrate a remarkable variability
      in phenotype, which hampers diagnostics. We performed a literature search, and
      analyzed 51 reported patients, using the originally reported patients as "gold
      standard." In 15 patients sufficient information and photographic evidence was
      available to confirm the clinical diagnosis. In 12 patients the diagnosis was
      suggestive but lack of data prevented a definite diagnosis, and in 24 patients an
      alternative diagnosis was likely. Core manifestations of the syndrome are marked
      pre-natal and severe post-natal growth retardation, an unusual face (triangular
      shape, sparse hair, small mouth, pointed chin), dental anomalies (natal teeth;
      hypodontia), generalized lipodystrophy with localized fat masses, and-in some
      cases-progressive ataxia and tremor. It has been suggested that the syndrome
      might be caused by biallelic variants in POLR3A, identified by exome sequencing
      in a single patient only. Therefore, we compared the WRS phenotype with
      characteristics of conditions known to be caused by autosomal recessively
      inherited POLR3A mutations. There are major differences but there are also
      similarities in phenotype, which sustain the suggestion that the syndrome can be
      caused by disturbed POLR3A functioning.

PMID- 28447408
TI  - Flow cytometry-Recognizing unusual populations in leukemia and lymphoma
      diagnosis.
AB  - Flow cytometry is an invaluable technology in the examination of blood, bone
      marrow, tissue and body fluids for the presence or absence of hematological
      disease. It is used in both diagnostic and follow-up testing, with an
      increasingly important role in the detection of very small residual disease
      populations (Minimal Residual Disease, MRD) However, flow cytometry
      immunophenotyping of leukemia and lymphoma is highly dependent on interpretation
      of results and with the increased complexity of 8-10 color instruments routinely
      used in clinical laboratories, knowledge of disease-defining populations is
      increasingly important as is recognizing normal and reactive patterns. This
      manuscript presents case studies with flow cytometric patterns encountered in
      routine screening of samples sent for leukemia and lymphoma immunophenotyping,
      focusing mainly on B-cell disorders which may be missed or incorrectly
      interpreted by the laboratory (including a hematopathologist) performing the
      test. Case studies are used to illustrate our laboratory's standardized approach
      to the interpretation of flow cytometric data. In addition to a standardized
      approach, these cases emphasize the importance of interpretative skills of
      technologist and hematopathologists in recognizing abnormal patterns in detecting
      hematological malignancies.

PMID- 28447406
TI  - The prenatal gut microbiome: are we colonized with bacteria in utero?
AB  - The colonization of the gut with microbes in early life is critical to the
      developing newborn immune system, metabolic function and potentially future
      health. Maternal microbes are transmitted to offspring during childbirth,
      representing a key step in the colonization of the infant gut. Studies of infant
      meconium suggest that bacteria are present in the foetal gut prior to birth,
      meaning that colonization could occur prenatally. Animal studies have shown that
      prenatal transmission of microbes to the foetus is possible, and physiological
      changes observed in pregnant mothers indicate that in utero transfer is likely in
      humans as well. However, direct evidence of in utero transfer of bacteria in
      humans is lacking. Understanding the timing and mechanisms involved in the first
      colonization of the human gut is critical to a comprehensive understanding of the
      early life gut microbiome. This review will discuss the evidence supporting in
      utero transmission of microbes from mother to infants. We also review sources of
      transferred bacteria, physiological mechanisms of transfer and modifiers of
      maternal microbiomes and their potential role in early life infant health. Well
      designed longitudinal birth studies that account for established modifiers of the
      gut microbiome are challenging, but will be necessary to confirm in utero
      transfer and further our knowledge of the prenatal microbiome.

PMID- 28447410
TI  - 2016 WHO Classification update-What's new in lymphoid neoplasms.
AB  - In the 8 years since the publication of the 4th edition of the WHO Classification
      of Hematopoietic and Lymphoid Tumours in 2008, there has been rapid accumulation
      of knowledge in the molecular genetics, biology, clinical behavior of many
      hematologic malignancies. Concepts and models have advanced to the point at which
      updates were deemed necessary prior to the formal WHO process of publication of a
      5th edition as part of the WHO "blue book" series. This overview will focus on
      lymphoid tumors and highlight important changes and updates to these neoplasms.

PMID- 28447409
TI  - Factor VIII inhibitors: Advances in basic and translational science.
AB  - In the treatment of hemophilia A, the 20%-30% risk of developing of anti-factor
      VIII (FVIII) antibodies, or inhibitors, is the dominant concern among healthcare
      providers. Immune tolerance induction remains the only effective method of
      eradicating inhibitors in approximately 75% of patients, but is accompanied by
      significant emotional and economical burden. While certain risk factors, such as
      the type of FVIII mutation, offer some insight, there remains no strategy to
      confidently predict the development of an inhibitor. Moreover, even if such a
      predictive tool existed, there is currently no proven protocol for tolerance
      induction of a previously untreated patient. In recent years, the growing body of
      knowledge concerning the fundamental immunology of inhibitors has shed light on
      potential therapeutic interventions. In this review, we highlight these new
      findings and their influences on translational medicine.

PMID- 28447411
TI  - Establishing reference intervals in the coagulation laboratory.
AB  - INTRODUCTION: Obtaining a reference interval (RI) is a challenge for any
      laboratory and becomes more complicated in the coagulation laboratory due to
      testing on samples with limited stability on reagents that are poorly
      standardized. Reference intervals are required to be able to evaluate results in
      relation to a patients' hemostatic disorder. This becomes one of the most
      important tasks conducted in the coagulation laboratory. However, many
      laboratories lack the time, finances and in many cases the expertise to conduct
      this study. METHODS: Many RI are obtained from package inserts, or from
      publications written by experts in lieu of laboratories conducting their own
      studies. An overview of validating reference intervals and options for verifying
      or transference of reference intervals is discussed. RESULTS: Based on the
      confidence interval and the acceptability of risk laboratories are willing to
      accept, coagulation laboratories have options to conduct robust studies for their
      RI. Data mining or global reference studies may help to provide data for age
      specific ranges. CONCLUSIONS: Pre-analytical variables and selection of healthy
      subjects have the largest impact on coagulation testing outcomes and need to be
      well controlled during the establishment of reference intervals. Laboratories
      have options in lieu of conducting a full validation on how to verify RI based on
      smaller RI studies or transference of RI after determining compatibility of the
      original RI study.

PMID- 28447412
TI  - Optimal utilization of thrombophilia testing.
AB  - The global incidence of venous thromboembolism is high so laboratory testing for
      hereditary thrombophilia and selected acquired thrombophilia is common. Given the
      costs associated with testing and multiple pre-analytic and analytic variables
      affecting the assays, careful patient selection and timing of testing and
      diligent application to patient management are critical to providing high-value
      clinical care. Collaboration between the ordering providers and performing
      laboratories has the potential to achieve these goals. Herein, utility of
      thrombophilia testing, variables that affect the assays, and impact on patient
      management are reviewed. Where available, information on cost-effectiveness is
      discussed.

PMID- 28447413
TI  - Laboratory measurement of the direct oral anticoagulants: Indications and impact
      on management in clinical practice.
AB  - Although the direct oral anticoagulants (DOACs) do not require routine laboratory
      monitoring, there may be special situations in which measurement of drug levels
      is desirable. There is a paucity of information on how measurement of DOAC levels
      is used in clinical practice. We conducted a retrospective cohort study of
      dabigatran, rivaroxaban, and apixaban levels measured at our institution. Of 9793
      patients with an active prescription for dabigatran, rivaroxaban, or apixaban in
      the electronic medical record during the 2.5-year study period, 32 (0.33%)
      patients underwent a total of 37 DOAC measurements. Twenty patients were on
      rivaroxaban, 12 were on apixaban, and none was on dabigatran. The most common
      indications for measurement in inpatients were surgery, breakthrough thrombosis,
      and bleeding. In the ambulatory setting, patient characteristics suspected to
      lead to derangements in drug levels (eg, extremes of body weight,
      gastrointestinal malabsorptive disorders) served as a frequent indication. Among
      preoperative patients, DOAC levels influenced decisions about the timing of
      surgery. In most outpatients, levels were within expected ranges and affirmed
      current management. In a small number of patients with breakthrough thrombosis or
      bleeding, the identification of drug levels below or above expected
      concentrations led to a change in the anticoagulant regimen. In conclusion, DOAC
      measurement was infrequently requested. Indications differed between hospitalized
      patients and outpatients. Clinical response varied by drug level and indication.

PMID- 28447414
TI  - Review of D-dimer testing: Good, Bad, and Ugly.
AB  - D-dimer assays are commonly used in clinical practice to exclude a diagnosis of
      deep vein thrombosis or pulmonary embolism. More recently, they have been also
      been used to guide patients with unprovoked venous thromboembolism (VTE) when
      faced with the decision to continue or stop anticoagulation after initial
      treatment is complete. D-dimer assays vary widely with respect to the antibody
      used, method of capture, instrumentation required, and calibration standard.
      These differences have an important influence on the operating characteristics of
      the assays. Consequently, the evidence available in the literature for one assay
      cannot simply be extrapolated to another. In this review, we will outline the
      general properties of D-dimer assays, discuss the concept of raising the D-dimer
      threshold used in diagnosis of VTE according to pretest probability and age, and
      provide clinical perspective on the role of D-dimer testing in the diagnosis and
      prognosis of VTE.

PMID- 28447415
TI  - The danger of relying on the APTT and PT in patients on DOAC therapy, a potential
      patient safety issue.
AB  - Prolongation of the activated partial thromboplastin time (APTT) and prothrombin
      time/international normalized ratio (PT/INR) correlates poorly with plasma
      concentrations of direct oral anticoagulant agents (DOACS) including direct
      thrombin and direct Xa inhibitors. It has been repeatedly demonstrated that
      patients can have normal APTT and PT/INR with a therapeutic plasma concentration
      of a DOAC. Clinicians can no longer rely on a normal APTT and PT to determine
      that an anticoagulated patient is safe to undergo an invasive procedure.
      Laboratory scientists need to play a key and active role in educating clinicians
      about the limitations of the APTT and PT in patients on DOAC prophylaxis or
      therapy.

PMID- 28447416
TI  - Microfluidics in flow cytometry and related techniques.
AB  - Technological advances in laboratory automation are now well understood and
      applied as they considerably improved the speed and robustness of haematological
      laboratory data, in the companion fields of blood analyzers and flow cytometry.
      Still rather confidential is the field of microfluidics, mostly confined so far
      to academic settings and research laboratories. The literature in the field of
      microfluidics is growing and applications in hematology range from cell counting
      to flow cytometry, cell sorting, or ex vivo testing. A literature search allows
      to identify many innovative solutions developed to master the specific physics of
      fluid movements in microchips. Miniaturization also dwells on findings that have
      emerged from different areas such as electronics and nanoengineering. This review
      proposes an overview of the major principles guiding developments in
      microfluidics and describes a necessarily limited and nonexhaustive series of
      specific applications. Readers are strongly encouraged to consult the documents
      referred to in the references section to learn more about this world knocking at
      our door and possibly liable to revolutionize our profession of hematology
      biologists in a not so far future.

PMID- 28447418
TI  - Preface.

PMID- 28447417
TI  - Diagnostic approach to microangiopathic hemolytic disorders.
AB  - Thrombotic micro-angiopathies (TMA) are a group of related disorders that are
      characterized by thrombosis of the microvasculature and associated organ
      dysfunction, and encompass congenital, acquired, and infectious etiologies. A
      hall mark of TMAs is the fragmentation of erythrocytes by the microvascular
      thrombi, resulting in a hemolytic anemia. There are several distinct
      pathophysiologies leading to microangiopathic hemolysis, ranging from decreased
      degradation of von Willebrand factor as seen in thrombotic thrombocytopenic
      purpura (TTP) to endothelial damage facilitated by Escherichia coli shiga toxin
      or complement dysregulation, seen in shiga toxin-related hemolytic-uremic
      syndrome (Stx-HUS) and complement-mediated TMA (also called atypical hemolytic
      uremic syndrome), respectively. Distinguishing these disorders is important, as
      many TMAs are life-threatening, the treatments are distinct and selecting
      appropriate therapy can improve patient prognosis. Laboratory testing, including
      measurement of ADAMTS13, ADAMTS13 inhibitor, shiga toxin, and complement factors,
      can help establish diagnoses and guide therapy.

PMID- 28447419
TI  - Controversies in the diagnosis of Type 1 von Willebrand disease.
AB  - von Willebrand disease (VWD) is the most common bleeding disorder. Type 1 VWD
      represents the majority of cases and results from a partial quantitative
      deficiency of von Willebrand factor (VWF). The diagnosis of Type 1 VWD presents
      many challenges, despite there being three established diagnostic criteria: a
      personal history of mucocutaneous bleeding, a family history and low VWF levels.
      These criteria do not always coexist, and there is great overlap of clinical
      phenotypes and laboratory parameters between healthy individuals and those with
      VWD. Mild bleeding symptoms can have any number of causes and bleeding is
      commonly reported in the general population. VWF levels do not always correlate
      with bleeding symptoms and can be variable between affected family members.
      Additionally, VWF levels vary widely as a result of both genetic and non-genetic
      influences. Perhaps the greatest current controversy in the diagnosis of Type 1
      VWD is that there is no consensus laboratory cut-off for the diagnosis, raising
      concern about both over- and under-diagnosis. Ongoing studies are addressing
      these issues by clarifying the underlying pathogenesis of the disease, as well as
      the natural history and the risk of future bleeding in those with the diagnosis.

PMID- 28447420
TI  - Red cell membrane disorders.
AB  - Significant advances have been made in our understanding of the structural basis
      for altered cell function in various inherited red cell membrane disorders with
      reduced red cell survival and resulting hemolytic anemia. The current review
      summarizes these advances as they relate to defining the molecular and structural
      basis for disorders involving altered membrane structural organization
      (hereditary spherocytosis [HS] and hereditary elliptocytosis [HE]) and altered
      membrane transport function (hereditary overhydrated stomatocytosis and
      hereditary xerocytosis). Mutations in genes encoding membrane proteins that
      account for these distinct red cell phenotypes have been identified. These
      molecular insights have led to improved understanding of the structural basis for
      altered membrane function in these disorders. Weakening of vertical linkage
      between the lipid bilayer and spectrin-based membrane skeleton leads to membrane
      loss in HS. In contrast, weakening of lateral linkages among different skeletal
      proteins leads to membrane fragmentation and decreased surface area in HE. The
      degrees of membrane loss and resultant increases in cell sphericity determine the
      severity of anemia in these two disorders. Splenectomy leads to amelioration of
      anemia by increasing the circulatory red cell life span of spherocytic red cells
      that are normally sequestered by the spleen. Disordered membrane cation
      permeability and resultant increase or decrease in red cell volume account for
      altered cellular deformability of hereditary overhydrated stomatocytosis and
      hereditary xerocytosis, respectively. Importantly, splenectomy is not beneficial
      in these two membrane transport disorders and in fact contraindicated due to
      severe postsplenectomy thrombotic complications.

PMID- 28447421
TI  - Clinical decision support for hematology laboratory test utilization.
AB  - Clinical decision support (CDS) is the use of information and communication
      technologies to improve clinical decision making and patient care. CDS
      applications have been used in many aspects of health care, including medication
      ordering and diagnostic prediction algorithms. As economic and regulatory
      pressures place a strain on laboratory resources, the potential of CDS to improve
      utilization of laboratory testing has also begun to be realized. Hematology and
      coagulation laboratories stand to gain tremendously from the implementation of
      CDS interventions, given their mixture of high-volume, low-cost tests (eg CBC,
      PT, aPTT) and tests that carry a high potential of being misused or
      misinterpreted (eg lupus anticoagulant, erythrocyte sedimentation rate, heparin
      induced thrombocytopenia testing). This brief review will define the key terms in
      the field of clinical decision support, provide instructive examples of CDS
      interventions to improve utilization of hematology and coagulation testing,
      introduce methods to implement these interventions effectively, and discuss
      metrics by which the success of these interventions can be evaluated.

PMID- 28447423
TI  - Update from the President on the International Society for Laboratory Hematology,
      including initiatives to promote education and best practices.

PMID- 28447424
TI  - Does morphology matter in 2017? An approach to morphologic clues in non
      neoplastic blood and bone marrow disorders.
AB  - Numerous non-neoplastic and neoplastic conditions manifest with distinctive
      features in blood. Although automated complete blood count (CBC) data are
      essential, CBC information alone is insufficient for diagnosis. Consequently,
      morphologic review of blood smears is still relevant in the era of sophisticated
      automated analyzer systems. Pathologist interpretation of the peripheral blood
      smear, in conjunction with CBC and clinical information, can provide rapid
      diagnostic information and guide cost-effective targeted laboratory testing.
      Pathologist review of blood smears can be used to diagnose cases in which the
      clinical findings are misleading or nonspecific. Here, we discuss a selection of
      cases in which the pathologist examination of the blood smear can aid in rapid
      and accurate diagnosis and guide appropriate treatment. Exemplary non-neoplastic
      disorders with distinctive morphologic blood features of RBC, neutrophils,
      monocytes, and lymphocytes will be highlighted. The differential diagnostic
      considerations in blood smears with RBC destruction will be presented, expanding
      beyond microangiopathic hemolytic anemia. Lymphocyte morphologic assessment
      guides differential diagnosis including the identification of rare germline
      disorders. In each case presented, the integration of morphologic features guided
      additional testing with confirmation of the diagnosis. Peripheral blood smear
      review is timely and cost effective, even in an era of sophisticated automated
      laboratory testing.

PMID- 28447422
TI  - Minimal residual disease in acute myelogenous leukemia.
AB  - Treatment of acute myelogenous leukemia (AML) over the past four decades remains
      mostly unchanged and the prognosis for the majority of patients remains poor.
      Most of the significant advances that have been observed are in defining
      cytogenetic abnormalities, as well as the genetic and epigenetic profiles of AML
      patients. While new cytogenetic and genetic aberrations such as the FLT3-ITD and
      NPM1 mutations are able to guide prognosis for the majority of patients with AML,
      outcomes are still dismal and relapse rates remain high. It is thought that
      relapse in AML is in part driven by minimal residual disease (MRD) that remains
      in the patient following treatment. Thus, there is a need for sensitive and
      objective methodology for MRD detection. Methodologies such as multiparameter
      flow cytometry (MFC), quantitative real-time polymerase chain reaction (RQ-PCR),
      digital PCR (dPCR), or next-generation sequencing (NGS) are being employed to
      evaluate their utility in MRD assessment. In this review, we will provide an
      overview of AML and the clinical utility of MRD measurement. We will discuss
      optimal timing to MRD measurement, the different approaches that are available,
      and efforts in the standardization across laboratories.

PMID- 28447425
TI  - Ten-color 15-antibody flow cytometry panel for immunophenotyping of lymphocyte
      population.
AB  - We have developed a lymphoproliferative disorder screening tube (LPD-ST) with the
      aim to provide comprehensive immunophenotyping of lymphocyte subsets with minimal
      need for additional testing. The LPD-ST consists of CD4/kappa FITC, CD8/lambda
      PE, CD3/CD14ECD, CD38PC5.5, CD20/CD56PC7, CD10APC, CD19APC-A700, CD5APC-A750,
      CD57/CD23PB and CD45KO. The LPD-ST was validated against previously used
      lymphocyte subset panels in Canada (n=60) and in Sweden (n=43) and against the
      OneFlowTM LST (n=60). The LPD-ST panel was then implemented in clinical practice
      using dried monoclonal antibody reagents (Duraclone(r) ) on 649 patient samples
      in Sweden. In 204 of 649 samples (31%), a monotypic B-cell population was found.
      Of these cases, a final diagnosis could be rendered in 106 cases (52%), and in
      the remainder, additional B-cell immunophenotyping was performed. In 20 (3%)
      samples, an aberrant T-cell population was confirmed by additional testing. Of
      425 samples diagnosed as normal/reactive lymphoid tissue, 50 (12%) required
      additional immunophenotyping, mostly due to an abnormal CD4/CD8 ratio. The LPD-ST
      tube significantly minimizes the need for additional testing, improves the turn
      around time, and reduces the cost of LPD immunophenotyping. It is also suitable
      for investigating paucicellular samples such as cerebrospinal fluid or fine
      needle aspirates.

PMID- 28447426
TI  - Next-generation sequencing as a tool for breakpoint analysis in rearrangements of
      the globin gene clusters.
AB  - INTRODUCTION: Next-generation sequencing (NGS), now embedded within genomic
      laboratories, is well suited to the detection of small sequence changes but is
      less well adapt for detecting structural variants (SV), mainly due to the
      relatively short sequence reads. Of the available target enrichment methods, bait
      capture or whole-genome sequencing appears better suited to detecting SV as there
      is less PCR amplification and is therefore more representative of the genome
      being sequenced. MATERIAL AND METHODS: In 2015, we described the first
      inversion/deletion causing epsilongammadeltabeta- thalassemia using an NGS
      approach, with base-pair resolution. Bioinformatic processing of the sequencing
      data was manual and time-consuming. The methodology relied on detecting the
      presence or absence of the SV by assessing sequence coverage and then mapping the
      deletion by capturing and sequencing breakpoint spanning reads (split reads). In
      the period between developing more automated analytical methods, we identified
      the first duplication of the entire beta globin cluster. RESULTS: Detecting the
      presence of the SV is reliable but capturing the breakpoint spanning reads is
      challenging. Confirmation by Sanger sequencing a breakpoint spanning amplicon has
      confirmed the NGS results in all cases. CONCLUSIONS: We have now streamlined and
      automated the bioinformatic approach using Exome Depth to assess sequence
      coverage and Delly to detect split and discordant reads. The combined NGS and
      bioinformatic strategy has proven to be highly successful and applicable to
      routine diagnostics.

PMID- 28447427
TI  - The utility of peripheral blood smear review for identifying specimens for flow
      cytometric immunophenotyping.
AB  - Laboratory professionals are in an ideal situation to identify CBC and peripheral
      blood smear findings that raise the possibility of a hematolymphoid neoplasm, and
      based on this information make recommendations for additional studies, such as
      flow cytometric immunophenotyping. In some circumstances a definitive diagnosis
      can be established from the combined peripheral blood morphologic and
      immunophenotypic findings obviating the need for bone marrow evaluation, such as
      for chronic lymphocytic leukemia. Occasionally flow cytometric studies are
      superior to morphologic assessment, such as in screening for hairy cell leukemia
      or identifying lymphocytic-variant hypereosinophilia. However, there is
      increasing recognition of small immunophenotypically unusual or abnormal
      populations of peripheral blood cells, particularly in older patients, which are
      of uncertain clinical significance, such as monoclonal B lymphocytosis and T-cell
      clonopathy. Therefore, it is important to integrate peripheral blood smear review
      findings with the clinical and other information before recommending flow
      cytometry. In addition, it is important to recognize situations where the results
      of peripheral blood smear review and flow cytometric immunophenotyping do not
      explain the clinical findings.

PMID- 28447429
TI  - Mind the gap-a European viewpoint on Alcoholics Anonymous.

PMID- 28447430
TI  - Commentary on Rehm et al. (2017): Composition of alcoholic beverages-an under
      researched dimension in the global comparative risk assessment.

PMID- 28447431
TI  - Commentary on Daubresse et al. (2017): An epidemic of outdated data.

PMID- 28447433
TI  - Serum vitamin D level is related to disease severity in pediatric alopecia
      areata.
AB  - BACKGROUND: Alopecia areata (AA) is the most common cause of inflammatory hair
      loss. AA is considered an autoimmune disease and occurs with various autoimmune
      disorders. Recent studies have revealed connection between autoimmune diseases
      and vitamin D deficiency. OBJECTIVES: In this study, we investigated vitamin D
      status in AA and its relationship with disease severity, number of patches, and
      disease duration. METHODS: This study included 20 pediatric patients with AA and
      34 pediatric healthy controls. The serum vitamin D levels were evaluated.
      RESULTS: The mean serum 25(OH)D concentration of patients was 15.47+/-7.66 ng/mL
      and of control group was 11.09+/-10.53 ng/mL. There was no statistically
      significant difference between two groups (P: .084). Vitamin D concentration had
      significantly and negatively correlated with SALT score (P<.001 and r: -.831),
      number of patch (P<.001 and r: -.989), and disease duration (P<.001 and r: 
      .997). CONCLUSION: Vitamin D deficiency is not the only etiologic factor in AA
      pathogenesis, but in the presence of other etiological factors, this deficiency
      can aggravate AA severity, and thus, vitamin D supplementation may be beneficial
      in treatment of pediatric AA.

PMID- 28447434
TI  - The influence of different muscle mass measurements on the diagnosis of cancer
      cachexia.
AB  - BACKGROUND: Progressive loss of muscle mass is a major characteristic of cancer
      cachexia. Consensus definitions for cachexia provide different options to measure
      muscle mass. This study describes the effect of different methods to determine
      muscle mass on the diagnosis of cancer cachexia. In addition, the association of
      cachexia with other features of cachexia, quality of life, and survival was
      explored. METHODS: Prior to chemotherapy, cachexia was assessed by weight loss,
      body mass index, and muscle mass measurements, the latter by mid-upper arm muscle
      area (MUAMA), computed tomography (CT) scans, and bio-electrical impedance
      analysis (BIA). In addition, appetite, inflammation, muscle strength, fatigue,
      quality of life, and survival were measured, and associations with cachexia were
      explored. RESULTS: Included were 241 patients with advanced cancer of the lung
      (36%), colon/rectum (31%), prostate (18%), or breast (15%). Mean age was 64 +/-
      10 years; 54% was male. Prevalence of low muscle mass was as follows: 13% with
      MUAMA, 59% with CT, and 93% with BIA. In turn, the prevalence of cachexia was 37,
      43, and 48%, whereby weight loss >5% was the most prominent component of being
      defined cachectic. Irrespective of type of muscle measurement, patients with
      cachexia presented more often with anorexia, inflammation, low muscle strength,
      and fatigue and had lower quality of life. Patients with cachexia had worse
      overall survival compared with patients without cachexia: HRs 2.00 (1.42-2.83)
      with MUAMA, 1.64 (1.15-2.34) with CT, and 1.50 (1.05-2.14) with BIA. CONCLUSIONS:
      Although the prevalence of low muscle mass in patients with cancer depended
      largely on the type of muscle measurement, this had little influence on the
      diagnosis of cancer cachexia (as the majority of patients was already defined
      cachectic based on weight loss). New studies are warranted to further elucidate
      the additional role of muscle measurements in the diagnosis of cachexia and the
      association with clinical outcomes.

PMID- 28447435
TI  - A Clinical Practice Guideline to Guide a System Approach to Diabetes Care in Hong
      Kong.
AB  - The Hospital Authority of Hong Kong is a statutory body that manages all the
      public medical care institutions in Hong Kong. There are currently around 400,000
      diabetic patients under its care at 17 hospitals (providing secondary care for
      40%) and 73 General Outpatient Clinics (providing primary care for 60%). The
      patient population has been growing at 6% to 8% per year over the past 5 years,
      estimated to include over 95% of all diagnosed patients in Hong Kong. In order to
      provide equitable and a minimal level of care within resources and local system
      factors constraints, a Clinical Practice Guideline on the management of type 2
      diabetes mellitus was drawn in 2013 to guide a system approach to providing
      diabetes care. There is an algorithm for the use of various hypoglycemic agents.
      An organizational drug formulary governs that less expansive options have to be
      used first. A number of clinical care and patient empowerment programs have been
      set up to support structured and systematic diabetes care. With such a system
      approach, there have been overall improvements in diabetes care with the
      percentage of patients with glycosylated hemoglobin <7% rising from 40% in 2010
      to 52% in 2015.

PMID- 28447436
TI  - Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and
      Insulin Resistance.
AB  - Obesity has quickly become a worldwide pandemic, causing major adverse health
      outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease
      and cancers. Obesity-induced insulin resistance is the key for developing these
      metabolic disorders, and investigation to understand the molecular mechanisms
      involved has been vibrant for the past few decades. Of these, low-grade chronic
      inflammation is suggested as a critical concept in the development of obesity
      induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO)
      signaling has been reported to be linked to improvement of insulin resistance in
      multiple organs involved in glucose metabolism. Recently, a body of evidence
      suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream
      mediator of NO signaling plays a crucial role in the anti-inflammatory effect and
      improvement of peripheral insulin resistance. These preclinical studies suggest
      that NO/VASP signaling could be an ideal therapeutic target in the treatment of
      obesity-related metabolic dysfunction. In this review, we introduce studies that
      investigated the protective role of NO/VASP signaling against obesity-related
      inflammation and insulin resistance in various tissues.

PMID- 28447437
TI  - Association between Blood Mercury Level and Visceral Adiposity in Adults.

PMID- 28447438
TI  - Diabetes Camp as Continuing Education for Diabetes Self-Management in Middle-Aged
      and Elderly People with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Despite the established benefits of diabetes camps for the continuing
      education of children with type 1 diabetes mellitus, little is known about the
      long-term metabolic benefits of diabetes camps for middle-aged and elderly people
      with type 2 diabetes mellitus (T2DM), especially in terms of glycosylated
      hemoglobin (HbA1c) variability. METHODS: The 1-year mean and variability of HbA1c
      before and after the diabetes camp was compared between the participants of the
      diabetes camp (n=57; median age 65 years [range, 50 to 86 years]; median diabetes
      duration 14 years [range, 1 to 48 years]). Additional case-control analysis
      compared the metabolic outcomes of the participants of the diabetes camp and
      their propensity score-matched controls who underwent conventional diabetes
      education (n=93). RESULTS: The levels of HbA1c during the first year after the
      diabetes camp were comparable to those of the matched controls (P=0.341). In an
      analysis of all participants of the diabetes camp, the 1-year mean+/-standard
      deviation (SD) of HbA1c decreased (P=0.010 and P=0.041) after the diabetes camp,
      whereas the adjusted SD and coefficient of variance (CV) of HbA1c did not
      decrease. The adjusted SD and CV significantly decreased after the diabetes camp
      in participants whose 1-year mean HbA1c was >=6.5% before the diabetes camp
      (n=40) and those with a duration of diabetes less than 15 years (n=32).
      CONCLUSION: The 1-year mean and SD of HbA1c decreased after the diabetes camp,
      with significant reduction in the adjusted SD and CV in those with higher
      baseline HbA1c and a shorter duration of diabetes.

PMID- 28447439
TI  - Lipid Abnormalities in Type 2 Diabetes Mellitus Patients with Overt Nephropathy.
AB  - BACKGROUND: Diabetic nephropathy is a major complication of diabetes and an
      established risk factor for cardiovascular events. Lipid abnormalities occur in
      patients with diabetic nephropathy, which further increase their risk for
      cardiovascular events. We compared the degree of dyslipidemia among type 2
      diabetes mellitus (T2DM) subjects with and without nephropathy and analyzed the
      factors associated with nephropathy among them. METHODS: In this retrospective
      study, T2DM patients with overt nephropathy were enrolled in the study group
      (n=89) and without nephropathy were enrolled in the control group (n=92). Both
      groups were matched for age and duration of diabetes. Data on total cholesterol
      (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low
      density lipoprotein cholesterol (LDL-C), urea and creatinine were collected from
      the case sheets. TG/HDL-C ratio, a surrogate marker for small, dense, LDL
      particles (sdLDL) and estimated glomerular filtration rate (eGFR) were calculated
      using equations. Multivariate analysis was done to determine the factors
      associated with eGFR. RESULTS: Dyslipidemia was present among 56.52% of control
      subjects and 75.28% of nephropathy subjects (P=0.012). The percentage of subjects
      with atherogenic dyslipidemia (high TG+low HDL-C+sdLDL) was 14.13 among controls
      and 14.61 among nephropathy subjects. Though serum creatinine was not
      significantly different, mean eGFR value was significantly lower among
      nephropathy patients (P=0.002). Upon multivariate analysis, it was found that TC
      (P=0.007) and HDL-C (P=0.06) were associated with eGFR among our study subjects.
      CONCLUSION: Our results show that dyslipidemia was highly prevalent among
      subjects with nephropathy. Regular screening for dyslipidemia may be beneficial
      in controlling the risk for adverse events among diabetic nephropathy patients.

PMID- 28447440
TI  - Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2
      Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial.
AB  - BACKGROUND: This is a subgroup analysis of Korean patients from a phase 3
      clinical trial investigating the efficacy and safety of ipragliflozin in patients
      with type 2 diabetes mellitus inadequately controlled with metformin. METHODS:
      This multicenter, placebo-controlled, double-blind, parallel-group study was
      carried out between November 2011 and January 2013. Patients entered a 2-week
      placebo pretreatment period, followed by a 24-week treatment period with either
      ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy
      outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body
      weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were
      measured and compared between the two treatment groups for patients enrolled in
      all 18 study sites in Korea. RESULTS: Eighty-two Korean patients received
      ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in
      HbA1c levels from baseline to the end of treatment were -0.97% in the
      ipragliflozin group and -0.31% in the placebo group, with an adjusted between
      group difference of -0.60% (P<0.001). Compared to placebo, FPG and body weight
      also decreased significantly (both P<0.001) from baseline after treatment in the
      ipragliflozin group, with between-group differences of -21.4 mg/dL and -1.53 kg,
      respectively. Decreased weight was the most common TEAE in the ipragliflozin
      group (7.0%); there were no reports of genital and urinary tract infection.
      CONCLUSION: Ipragliflozin treatment in addition to metformin led to significant
      improvement in glycemic outcomes and reduction in body weight in Korean patients
      with type 2 diabetes mellitus, compared with metformin treatment alone; the
      safety profile was comparable in both groups.

PMID- 28447441
TI  - A Cutoff for Age at Menarche Predicting Metabolic Syndrome in Egyptian
      Overweight/Obese Premenopausal Women.
AB  - Previous studies showed that early age at menarche is associated with increased
      risk of metabolic syndrome. However, the definition of early menarche at these
      studies was based on background data in the communities at which these studies
      was carried on. The aim of this work is to determine a cutoff for age at menarche
      discriminating presence or absence of metabolic syndrome in overweight/obese
      premenopausal women. This study included 204 overweight/obese women. Metabolic
      syndrome was defined according to NCEP-ATP III (National Cholesterol Education
      Program Adult Treatment Panel III) criteria. Of a total 204 participants, 82
      (40.2%) had metabolic syndrome. By using receiver operating characteristic
      analysis, age at menarche <=12.25 year discriminated individuals with from those
      without metabolic syndrome. The area under the curve was 0.76 (95% confidence
      interval, 0.70 to 0.83). Sensitivity, specificity, negative predictive value, and
      positive predictive value were 82%, 70%, 85%, and 64%, respectively. Age at
      menarche <=12.25 years predicts the presence of metabolic syndrome in
      overweight/obese women.

PMID- 28447442
TI  - Letter: Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia
      in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23
      30).

PMID- 28447443
TI  - Response: Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia
      in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23
      30).

PMID- 28447445
TI  - Myomectomy: technique and current indications.
AB  - Uterine fibroids are the commonest benign tumor of the female genital tract. They
      affect a significant proportion of reproductive aged women and may cause
      excessive menstrual bleeding, pelvic pain or pressure, and adversely affect
      reproductive outcomes. However, many women remain asymptomatic. Fibroids are the
      first indication for hysterectomy, but myomectomy is the most suitable surgical
      option for women who desire preservation of their fertility potential. Only a
      selected group of women of childbearing age will benefit from a myomectomy, as
      the consequences of myomectomy on reproductive function have remained
      controversial. The purpose of this paper was to review the main surgical
      approaches for myomectomy, and discuss evidence-based indications for myomectomy
      in women with fibroids, especially with regards to its impact on fertility and
      reproductive outcomes. A critical review of the literature pertaining to the
      surgical approaches of myomectomy and the indications for myomectomy was
      performed, focusing on their impact on fertility and reproductive outcomes.
      Myomectomy is useful for the treatment of symptomatic fibroids and in selected
      women with infertility. Symptomatic submucosal fibroids are classically treated
      by hysteroscopic resection. Symptomatic intramural and subserosal fibroids may be
      treated by myomectomy, either by laparotomy or laparoscopy depending on their
      number and size. Prophylactic myomectomy is not recommended for preventing
      obstetrical complications or the risk of leiomyosarcoma. Although fibroids may
      have a negative effect on fertility, only the removal of submucosal fibroids has
      been consistently shown to improve spontaneous fertility or outcomes of assisted
      reproduction technology.

PMID- 28447444
TI  - Maternal thyroid function in women undergoing controlled ovarian hyperstimulation
      during in-vitro fertilization and its relation to reproductive outcome.
AB  - BACKGROUND: We conducted a study to evaluate the changes in thyroid function
      during controlled ovarian hyperstimulation (COH) and its association with the
      outcome of assisted reproductive technique (ART). METHODS: This is a prospective
      cohort study done in University Hospital Fertility Clinic for one year duration.
      A total of 88 euthyroid women who underwent COH as part of planned in-vitro
      fertilization (IVF) were invited to participate in this study. Serum thyroid
      function of each women will be monitored before stimulation (T1), day 10-13 of
      cycle (T2), during oocyte retrieval (T3), one week following embryo transfer
      (T4), and at four weeks after embryo transfer (T5). Reproductive outcome of IVF
      will be observed and documented. RESULTS: Nine women had ongoing singleton
      pregnancy, seven suffered from miscarriage, while the rest had implantation
      failure. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4)
      increased throughout stimulation, peaking at 32-36 hours after hCG administration
      compared to baseline (1.250 vs. 1.740 mIU/L and 13.94 vs. 15.25 pmol/L). It
      remains elevated until one week following embryo transfer. The increment of serum
      TSH exceeded the upper limit, acceptable for first trimester (<1.60 mIU/L).
      However, the evolution of serum TSH and fT4 did not significantly differ with
      pregnancy outcome. CONCLUSIONS: In euthyroid women, thyroid function changed
      significantly during COH, but these changes were not different between the three
      reproductive outcomes. Thus, we do not suggest continuous thyroid function
      monitoring during COH.

PMID- 28447446
TI  - Highly Conductive Transparent and Flexible Electrodes Including Double-Stacked
      Thin Metal Films for Transparent Flexible Electronics.
AB  - To keep pace with the era of transparent and deformable electronics, electrode
      functions should be improved. In this paper, an innovative structure is suggested
      to overcome the trade-off between optical and electrical properties that commonly
      arises with transparent electrodes. The structure of double-stacked metal films
      showed high conductivity (<3 Omega/sq) and high transparency (~90%)
      simultaneously. A proper space between two metal films led to high transmittance
      by an optical phenomenon. The principle of parallel connection allowed the
      electrode to have high conductivity. In situ fabrication was possible because the
      only materials composing the electrode were silver and WO3, which can be
      deposited by thermal evaporation. The electrode was flexible enough to withstand
      10 000 bending cycles with a 1 mm bending radius. Furthermore, a few MUm scale
      patterning of the electrode was easily implemented by using photolithography,
      which is widely employed industrially for patterning. Flexible organic light
      emitting diodes and a transparent flexible thin-film transistor were successfully
      fabricated with the proposed electrode. Various practical applications of this
      electrode to new transparent flexible electronics are expected.

PMID- 28447447
TI  - Nuclear-Targeting Gold Nanorods for Extremely Low NIR Activated Photothermal
      Therapy.
AB  - Photorelated nanomedicine is of particular interest as an emerging paradigm
      toward precise cancer therapy, as demonstrated by recent developments of
      photothermal therapy (PTT), an emerging technique employing light-converting
      agents to burn cancerous cells by overdosed optical energy-converted heat.
      However, most of the laser irradiations needed for effective PTT significantly
      exceed the maximal permissible power density in human skin, which is likely to
      damage surrounding normal tissues. Herein, we report a strategy of intranuclear
      PTT of cancer enabled by nuclear-targeted delivery of gold nanorods of ~10.5 *
      40.5 nm in size via conjugation with nuclear location signal peptides (GNRs-NLS)
      under an extremely low near-infrared irradiation of 0.2 W/cm2, much below the
      maximal permissible exposure of skin. Interestingly, we found that a mild but
      nuclear-focused temperature increase generated by GNRs-NLS is sufficient to cause
      damage to intranuclear DNA and the inhibition of DNA repair process, which,
      interestingly, led to the cancer cell apoptosis rather than to conventional cell
      necrosis by thermal ablation during PTT. Correspondingly, tumors treated with
      GNRs-NLS exhibited gradual but significant regressions rather than traditional
      harsh burning-up of tumors, in comparison with negligible antitumor effect by
      GNRs without nuclear targeting under the same ultralow NIR irradiation. This
      report demonstrates the successful intranuclear efficient photothermal therapy of
      cancer via cell apoptosis by photoadsorbing agents, e.g., GNRs-NLS in the present
      case, with largely mitigated side-effect on normal tissues and therefore
      substantially improved biosafety.

PMID- 28447448
TI  - Lanthanide-Organic Gels as a Multifunctional Supramolecular Smart Platform.
AB  - A multifunctional smart supramolecular platform based on a lanthanide-organic
      hydrogel is presented. This platform, which provides unique biocompatibility and
      tunable optical properties, is synthesized by a simple, fast, and reproducible
      eco-friendly microwave-assisted route. Photoluminescent properties enable the
      production of coated light-emitting diodes (LED), unique luminescent barcodes
      dependent on the excitation wavelength and thin-films for use in tamper seals.
      Moreover, piroxicam entrapped in hydrogel acts as a transdermal drug release
      device efficient in inhibiting edemas as compared to a commercial reference.

PMID- 28447449
TI  - Molecular Simulations of Mixed Lipid Bilayers with Sphingomyelin,
      Glycerophospholipids, and Cholesterol.
AB  - The highly diversified composition of lipid bilayers across living cells is
      crucial for many biological processes. Lipid bilayers mainly consist of
      phosphatidylcholines (PC), phosphatidylethanolamines (PE), sphingomyelin (SM),
      and cholesterol, with eukaryotic membranes containing high percentage of
      sphingomyelin and cholesterol. In this study, we have modeled bilayers with
      different concentration of PC, PE, and SM to understand the changes in bilayer
      properties with varied SM concentrations. In addition, membrane models with 33%
      cholesterol have been simulated to understand the influence of cholesterol. To
      quantitatively access the structure and dynamics of membranes, deuterium order
      parameters (SCD), mass density profiles, lipid relaxation times, clustering
      analysis, and radial distribution functions are calculated. The SCDs compare
      favorably with past NMR experiments and increase with an increase in SM content.
      The surface area calculations showed that on addition of 50% palmitoyl-SM (PSM)
      surface area decreases (60.0 +/- 0.6 A2) from that of pure POPC (64.7 A2), which
      is further lowered in the presence of cholesterol (44.4 +/- 0.2 A2). The lipid
      axial relaxation time decreases with increase in concentration of
      glycerophospholipids. The accuracy of these lipid membranes allows for future
      studies with more complex lipid mixtures containing SM to represent the diversity
      of lipids in natural membranes.

PMID- 28447450
TI  - Band-Bending of Ga-Polar GaN Interfaced with Al2O3 through Ultraviolet/Ozone
      Treatment.
AB  - Understanding the band bending at the interface of GaN/dielectric under different
      surface treatment conditions is critically important for device design, device
      performance, and device reliability. The effects of ultraviolet/ozone (UV/O3)
      treatment of the GaN surface on the energy band bending of atomic-layer
      deposition (ALD) Al2O3 coated Ga-polar GaN were studied. The UV/O3 treatment and
      post-ALD anneal can be used to effectively vary the band bending, the valence
      band offset, conduction band offset, and the interface dipole at the Al2O3/GaN
      interfaces. The UV/O3 treatment increases the surface energy of the Ga-polar GaN,
      improves the uniformity of Al2O3 deposition, and changes the amount of trapped
      charges in the ALD layer. The positively charged surface states formed by the
      UV/O3 treatment-induced surface factors externally screen the effect of
      polarization charges in the GaN, in effect, determining the eventual energy band
      bending at the Al2O3/GaN interfaces. An optimal UV/O3 treatment condition also
      exists for realizing the "best" interface conditions. The study of UV/O3
      treatment effect on the band alignments at the dielectric/III-nitride interfaces
      will be valuable for applications of transistors, light-emitting diodes, and
      photovoltaics.

PMID- 28447451
TI  - Improvement of a P450-Based Recombinant Escherichia coli Whole-Cell System for
      the Production of Oxygenated Sesquiterpene Derivatives.
AB  - Sesquiterpenes are common constituents of essential oil in plants. Their
      oxygenated derivatives often possess desirable flavor, fragrance, and
      pharmaceutical properties. Recently, the CYP264B1-based recombinant Escherichia
      coli whole-cell system has been constructed for the oxidation of sesquiterpenes.
      However, limiting factors of this system related to the high volatility of
      substrates and the suitability of the P450 redox partner need to be addressed. In
      this work, the improvement of the system was implemented with (+)-alpha
      longipinene as a model substrate. By using 2-hydroxypropyl-beta-cyclodextrin and
      an alternative ferredoxin reductase, the conversion of (+)-alpha-longipinene was
      improved 77.1%. Applying the optimized conditions, the yields of the main
      products were 54.2, 34.2, and 47.2 mg L-1, corresponding to efficiencies of 82.1,
      51.8, and 71.5% for the conversion of (+)-alpha-longipinene, (-)-isolongifolene,
      and alpha-humulene, respectively, at a 200 mL scale. These products were
      characterized as 12-hydroxy-alpha-longipinene, isolongifolene-9-one, and 5
      hydroxy-alpha-humulene, respectively, by nuclear magnetic resonance spectroscopy.

PMID- 28447452
TI  - Single Usage of a Kitchen Degreaser Can Alter Indoor Aerosol Composition for
      Days.
AB  - To the best of our knowledge, this study represents the first observation of
      multiday persistence of an indoor aerosol transformation linked to a kitchen
      degreaser containing monoethanol amine (MEA). MEA remaining on the cleaned
      surfaces and on a wiping paper towel in a trash can was able to transform
      ammonium sulfate and ammonium nitrate into (MEA)2SO4 and (MEA)NO3. This influence
      persisted for at least 60 h despite a high average ventilation rate. The
      influence was observed using both offline (filters, impactors, and ion
      chromatography analysis) and online (compact time-of-flight aerosol mass
      spectrometer) techniques. Substitution of ammonia in ammonium salts was observed
      not only in aerosol but also in particles deposited on a filter before the
      release of MEA. The similar influence of other amines is expected based on
      literature data. This influence represents a new pathway for MEA exposure of
      people in an indoor environment. The stabilizing effect on indoor nitrate also
      causes higher indoor exposure to fine nitrates.

PMID- 28447453
TI  - A Computational Selection of Metabolite Biomarkers Using Emerging Pattern Mining:
      A Case Study in Human Hepatocellular Carcinoma.
AB  - The biomarker development in metabolomics aims at discriminating diseased from
      normal subjects and at creating a predictive model that can be used to diagnose
      new subjects. From a case study on human hepatocellular carcinoma (HCC), we
      studied for the first time the potential usefulness of the emerging patterns
      (EPs) that come from the data mining domain. When applied to a metabolomics data
      set labeled with two classes (e.g., HCC patients vs healthy subjects), EP mining
      can capture differentiating combinations of metabolites between the two classes.
      We observed that the so-called jumping emerging patterns (JEPs), which correspond
      to the combinations of metabolites that occur in only one of the two classes,
      achieved better performance than individual biomarkers. Particularly, the
      implementation of the JEPs in a rules-based diagnostic tool drastically reduced
      the false positive rate, i.e., the rate of healthy subjects predicted as HCC
      patients.

PMID- 28447454
TI  - Mycochemical Changes Induced by Selenium Enrichment in P. ostreatus Fruiting
      Bodies.
AB  - The effects of selenium enrichment on the biological efficiency, phenolic
      compounds, amino acid profile, antioxidant capacity, and cellular antioxidant
      activity (CAA) were evaluated in Pleurotus ostreatus fruiting bodies (FB)
      harvested during three sequential flushes. Sodium selenate was used to reach
      selenium content of 17.5 or 5.8 mg/kg in the sorghum straw substrate. Biological
      efficiency and total selenium content increased. One of the main differences
      among treatments was in ergothioneine content, an indicator of oxidative stress
      that was positively related with valine and isoleucine contents and negatively
      related to leucine and phenylalanine. Besides ergothioneine, nucleosides derived
      from adenine and uracyl were the major peaks observed in all treatments, and
      coumaric and ferulic acids were found in the bound phenolics extract. Selenium
      enrichment also affected the antioxidant capacity, and particularly the
      methanolic extract obtained from the second flush of FB cultivated in selenium
      enriched substrate (17.5 mg/kg) had the best CAA.

PMID- 28447455
TI  - Efficiency and Safety of beta-CD-(D3)7 as siRNA Carrier for Decreasing Matrix
      Metalloproteinase-9 Expression and Improving Wound Healing in Diabetic Rats.
AB  - Overexpression of matrix metalloproteinase-9 (MMP-9) is critical for diabetic
      chronic wounds involved in the refractory wound healing process. We aimed to
      develop a strategy through RNAi to decrease MMP-9 expression and improve diabetic
      wound healing. We had explored beta-CD-(D3)7 as a gene carrier to take siRNA and
      effectively interfere with MMP-9 expression. It has been proven that beta-CD
      (D3)7 could be used as an effective siRNA delivery system. In this study, we want
      to know about the efficiency and safety of beta-CD-(D3)7/MMP-9 siRNA for
      improving wound healing in diabetic rats. beta-CD-(D3)7/MMP-9 siRNA treated
      animals show lower levels of MMP-9 expression, which induce faster wound-close
      rates. Histological evaluation indicates that beta-CD-(D3)7/MMP-9 siRNA
      significantly increases the content of collagen around the injured tissues. The
      number of neutrophilic ganulocytes was significantly decreased through treatment
      of beta-CD-(D3)7/MMP-9 siRNA. In vivo fluorescence imaging assessment shows that
      beta-CD-(D3)7/MMP-9 siRNA could not cause organ damage and organ accumulation.
      The results suggest that beta-CD-(D3)7/MMP-9 siRNA might be developed as a novel
      topical agent for the diabetic wounds treatment.

PMID- 28447457
TI  - Co3O4-delta Quantum Dots As a Highly Efficient Oxygen Evolution Reaction Catalyst
      for Water Splitting.
AB  - Co3O4-delta quantum dots (Co3O4-delta-QDs) with a crystallite size of
      approximately 2 nm and oxygen vacancies were fabricated through multicycle
      lithiation/delithiation of mesoporous Co3O4 nanosheets. Used as an oxygen
      evolution reaction (OER) electrocatalyst for water splitting, the catalytic
      performance (an overpotential of 270 mV@10 mA cm-2 and no decay within 30 h) of
      Co3O4-delta-QDs is superior to that of previously reported Co-based catalysts and
      the state-of-the-art IrO2. Compared to that of the Co3O4 nanosheets, the enhanced
      OER activity of Co3O4-delta-QDs is attributed to two factors: one is the
      increased quantity of the Faradaic active sites, including the total active sites
      (q*Total), the most accessible active sites (q*Outer), and their ratio
      (q*Outer/q*Total); the other is the enhanced intrinsic electroactivity per active
      site evaluated by the turnover frequency and the current density normalized by
      the most accessible active sites (j/q*Outer) related to the OER. This multicycle
      lithiation/delithiation method can be applied to other transition metal oxides as
      well, offering a general approach to develop high-performance electrocatalysts
      for water splitting.

PMID- 28447456
TI  - Numerical Modeling of Electroosmotic Push-Pull Perfusion and Assessment of Its
      Application to Quantitative Determination of Enzymatic Activity in the
      Extracellular Space of Mammalian Tissue.
AB  - Many sampling methods have been developed to measure the extracellular
      concentrations of solutes in the extracellular space of mammalian tissue, e.g.,
      brain. However, few have been used to quantitatively study the various processes,
      such as enzymatic degradation, that determines the fate of these solutes. For a
      method to be useful in this pursuit, it must be able to (1) perfuse tissue and
      collect the perfusate for quantitative analysis of the solutes introduced and
      reaction products produced, (2) control the average residence time of the active
      solutes, and (3) have the appropriate spatial resolution for the process of
      interest. Our lab previously developed a perfusion technique based on
      electroosmosis (EO), called EO push-pull perfusion (EOPPP), that is in principle
      suitable to meet these needs. However, much like the case for other sampling
      methods that came before, there are parameters that are needed for quantitative
      interpretation of data but that cannot be measured easily (or at all). In this
      paper, we present a robust finite element model that provides a deep
      understanding of fluid dynamics and mass transport in the EOPPP method, assesses
      the general applicability of EOPPP to studying enzyme activity in the ECS, and
      grants a simple approach to data treatment and interpretation to obtain, for
      example, Vmax and Km for an enzymatic reaction in the extracellular space of the
      tissue. This model is a valuable tool in optimizing and planning experiments
      without the need for costly experiments.

PMID- 28447458
TI  - Nickel-Catalyzed Directed C6-Selective C-H Alkylation of 2-Pyridones with Dienes
      and Activated Alkenes.
AB  - A pyridine-directed, C6-selective nickel-catalyzed ring-contracting C-H
      alkylation of 2-pyridones with 1,5-cyclooctadiene (cod) has been developed. The
      reaction proceeds smoothly under external-ligand-free conditions and is
      accelerated uniquely by a K3PO4 base. Preliminary mechanistic investigations with
      deuterium-labeled substrates and related reactions with some alkenes are also
      disclosed.

PMID- 28447459
TI  - Fast Torsional Artificial Muscles from NiTi Twisted Yarns.
AB  - Torsional artificial muscles made of multiwalled carbon nanotube/niobium nanowire
      yarns have shown remarkable torsional speed and gravimetric torque. The muscle
      structure consists of a twisted yarn with half of its length infiltrated with a
      stimuli-responsive guest material such as paraffin wax. The volumetric expansion
      of the guest material creates the torsional actuation in the yarn. In the present
      work, we show that this type of actuation is not unique to wax-infiltrated carbon
      multiwalled nanotube (MWCNT) or niobium nanowire yarns and that twisted yarn of
      NiTi alloy fibers also produces fast torsional actuation. By gold-plating half
      the length of a NiTi twisted yarn and Joule heating it, we achieved a fully
      reversible torsional actuation of up to 16 degrees /mm with peak torsional speed
      of 10 500 rpm and gravimetric torque of 8 N.m/kg. These results favorably compare
      to those of MWCNTs and niobium nanowire yarns.

PMID- 28447460
TI  - Effects of Histidine Supplementation on Global Serum and Urine 1H NMR-based
      Metabolomics and Serum Amino Acid Profiles in Obese Women from a Randomized
      Controlled Study.
AB  - The aim of current study was to investigate the metabolic changes associated with
      histidine supplementation in serum and urine metabolic signatures and serum amino
      acid (AA) profiles. Serum and urine 1H NMR-based metabolomics and serum AA
      profiles were employed in 32 and 37 obese women with metabolic syndrome (MetS)
      intervened with placebo or histidine for 12 weeks. Multivariable statistical
      analysis were conducted to define characteristic metabolites. In serum 1H NMR
      metabolic profiles, increases in histidine, glutamine, aspartate, glycine,
      choline, and trimethylamine-N-oxide (TMAO) were observed; meanwhile, decreases in
      cholesterol, triglycerides, fatty acids and unsaturated lipids, acetone, and
      alpha/beta-glucose were exhibited after histidine supplement. In urine 1H NMR
      metabolic profiles, citrate, creatinine/creatine, methylguanidine, and betaine +
      TMAO were higher, while hippurate was lower in histidine supplement group. In
      serum AA profiles, 10 AAs changed after histidine supplementation, including
      increased histidine, glycine, alanine, lysine, asparagine, and tyrosine and
      decreased leucine, isoleucine, ornithine, and citrulline. The study showed a
      systemic metabolic response in serum and urine metabolomics and AA profiles to
      histidine supplementation, showing significantly changed metabolism in AAs,
      lipid, and glucose in obese women with MetS.

PMID- 28447461
TI  - Diffusion-Controlled Recrystallization of Water Sorbed into Poly(meth)acrylates
      Revealed by Variable-Temperature Mid-Infrared Spectroscopy and Molecular Dynamics
      Simulation.
AB  - Recrystallization behaviors of water sorbed into four poly(meth)acrylates, poly(2
      methoxyethyl acrylate), poly(tetrahydrofurfuryl acrylate), poly(methyl acrylate),
      and poly(methyl methacrylate), are investigated by variable-temperature mid
      infrared (VT-MIR) spectroscopy and molecular dynamics (MD) simulation. VT-MIR
      spectra demonstrate that recrystallization temperatures of water sorbed into the
      polymers are positively correlated with their glass-transition temperatures
      reported previously. The present MD simulation shows that a lower-limit
      temperature of the diffusion for the sorbed water and the glass-transition
      temperatures of the polymers also have a positive correlation, indicating that
      the recrystallization is controlled by diffusion mechanism rather than
      reorientation mechanism. Detailed molecular processes of not only
      recrystallization during rewarming but also crystallization during cooling and
      hydrogen-bonding states of water in the polymers are systematically analyzed and
      discussed.

PMID- 28447462
TI  - I2-Catalyzed Oxidative N-S Bond Formation: Metal-Free Regiospecific Synthesis of
      N-Fused and 3,4-Disubstituted 5-Imino-1,2,4-thiadiazoles.
AB  - A novel and expeditious approach for the synthesis of N-fused and 3,4
      disubstituted 5-imino-1,2,4-thiadiazole derivatives has been achieved through the
      molecular iodine-catalyzed oxidative cyclization of 2-aminopyridine/amidine and
      isothiocyanate via N-S bond formation at ambient temperature. The present one-pot
      transition-metal-free protocol provides the facile and highly efficient
      regiospecific synthesis of various 1,2,4-thiadiazole derivatives in a scaled-up
      manner with good to excellent yields using inexpensive I2 as a catalyst.

PMID- 28447463
TI  - Screening of Debaryomyces hansenii Strains for Flavor Production under a Reduced
      Concentration of Nitrifying Preservatives Used in Meat Products.
AB  - A total of 15 Debaryomyces hansenii strains from different food origins were
      genetically characterized and tested on a culture medium resembling the
      composition of fermented sausages but different concentrations of nitrifying
      preservatives. Genetic typing of the D. hansenii strains revealed two levels of
      discrimination: isolation source or strain specific. Different abilities to
      proliferate on culture media containing different concentrations of nitrate and
      nitrite, as sole nitrogen sources and in the presence of amino acids, were
      observed within D. hansenii strains. Overall metabolism of amino acids and
      generation of aroma compounds were related to the strain origin of isolation. The
      best producers of branched aldehydes and ethyl ester compounds were strains
      isolated from pork sausages. Strains from cheese and llama sausages were good
      producers of ester compounds and branched alcohols, while vegetable strains
      produced mainly acid compounds. Nitrate and nitrite reduction affected in
      different ways the production of volatiles by D. hansenii.

PMID- 28447464
TI  - Impact of Lipid Phase on the Bioavailability of Vitamin E in Emulsion-Based
      Delivery Systems: Relative Importance of Bioaccessibility, Absorption, and
      Transformation.
AB  - A simulated gastrointestinal tract/Caco-2 cell culture model was used to
      investigate the effects of lipid phase type on vitamin E (VE) bioavailability.
      Oil-in-water emulsions fortified with alpha-tocopherol acetate were fabricated
      using a natural emulsifier (quillaja saponin) and long or medium chain
      triglycerides (LCTs or MCTs) as lipids. The impact of lipid type on VE
      bioaccessibility, absorption, and transformation was determined. VE
      bioaccessibility was greater for LCT (46%) than MCT (19%) due to greater
      solubilization in mixed micelles assembled from longer fatty acids. VE absorption
      by Caco-2 cells was similar for LCT (28%) and MCT (30%). The transformation of
      alpha-tocopherol acetate to alpha-tocopherol was higher for LCT (90%) than MCT
      (75%) due to differences in esterase accessibility to VE. Emulsion-based delivery
      systems formulated using LCT are therefore more suitable for encapsulating and
      delivering vitamin E than those formulated using MCT.

PMID- 28447465
TI  - Transferrin-Dressed Virus-like Ternary Nanoparticles with Aggregation-Induced
      Emission for Targeted Delivery and Rapid Cytosolic Release of siRNA.
AB  - Viruses have evolved to be outstandingly efficient at gene delivery, but their
      use as vectors is limited by safety risks. Inspired by the structure of viruses,
      we constructed a virus-mimicking vector (denoted as TR4@siRNA@Tf NCs) with virus
      like architecture and infection properties. Composed of a hydrophilic peptide, an
      aggregation-induced emission (AIE) luminogen, and a lipophilic tail, TR4 imitates
      the viral capsid and endows the vector with AIE properties as well as efficient
      siRNA compaction. The outer glycoprotein transferrin (Tf) mimics the viral
      envelope protein and endows the vector with reduced cytotoxicity as well as
      enhanced targeting capability. Because of the strong interaction between Tf and
      transferrin receptors on the cell surface, the Tf coating can accelerate the
      intracellular release of siRNA into the cytosol. Tf and TR4 are eventually cycled
      back to the cell membrane. Our results confirmed that the constructed
      siRNA@TR4@Tf NCs show a high siRNA silencing efficiency of 85% with significantly
      reduced cytotoxicity. These NCs have comparable transfection ability to natural
      viruses while avoiding the toxicity issues associated with typical nonviral
      vectors. Therefore, this proposed virus-like siRNA vector, which integrates the
      advantages of both viral and nonviral vectors, should find many potential
      applications in gene therapy.

PMID- 28447466
TI  - Results of a Randomized Trial on an Intervention Promoting Adoption of
      Occupational Sun Protection Policies.
AB  - PURPOSE: To evaluate an intervention promoting adoption of occupational sun
      protection policies by employers in a randomized trial. DESIGN: A randomized
      pretest-posttest controlled design with 2-year follow-up was conducted in 2010 to
      2013. SETTING: Local government organizations in Colorado who had outdoor workers
      in public works, public safety, and/or parks and recreation. PARTICIPANTS: Ninety
      eight local government organizations (n = 51 municipalities, 10 counties, and 37
      special districts). INTERVENTION: Organizations were randomly assigned to receive
      a policy and education intervention comprised of personal contacts and theory
      based training and materials or to an attention control group. MEASURES:
      Occupational policy documents were coded for sun safety content by a trained
      research assistant blind to condition. ANALYSIS: Policy scores were analyzed with
      logistic and Poisson regression models using imputation. RESULTS: At posttest,
      more organizations in the intervention group had a sun protection policy than in
      the control group (odds ratio [OR] = 4.91, P < .05; intent to treat: OR = 5.95, P
      < .05) and policies were more extensive (chi2 = 31.29, P < .01; intent to treat:
      chi2 =73.79, P < .01) and stronger (chi2 = 24.50, P < .01; intent to treat: chi2
      = 51.95, P < .01). Policy adoption was higher when the number of contacts and
      trainings increased ( P < .05). CONCLUSION: The intervention had a large effect
      on adoption of formal sun protection policies, perhaps because of its fit with
      legal requirements to maintain safe workplaces. Personal contacts with managers
      were influential on adoption of occupational policy even in this age of
      communication technology and social media.

PMID- 28447467
TI  - Perinatal and infant mental health in Australia: moving forward towards REAL
      prevention and early intervention - can we do it?
AB  - OBJECTIVES: Australia has been at the forefront of appropriate early
      intervention. Prevention of mental illness in infants by early identification and
      intervention in the mental health of their mothers has stalled since the
      cessation of funding through the National Perinatal Depression Initiative (NPDI,
      2009-2015). Whilst screening for maternal mental illness has been widely
      implemented throughout Australia during the last two decades, services are now
      diminishing and great opportunities to ride the crest of a wave for appropriate
      mental illness intervention are receding. Reviews of history and interventions
      internationally may help guide future directions. CONCLUSIONS: Advocacy through
      across-agency and across-political-party support has been markedly successful for
      perinatal and infant mental health in the United Kingdom. A solid foundation
      exists in Australia. Australian psychiatrists have the ability to continue to
      change the face of prevention and early intervention.

PMID- 28447468
TI  - Induction of apoptosis in the bursa of Fabricius by vaccination against Gumboro
      disease.
AB  - Infectious bursal disease is a severe acute viral disease of young chickens,
      affecting mainly the B-lymphocytes in the bursa of Fabricius, leading to severe
      immunosuppression as a result of the death of lymphoid cells. In the bursa
      infected with infectious bursal disease virus, viral replication is associated
      with apoptosis of lymphoid cells, inflammatory change and atrophy. Vaccination
      has appeared to be a crucial factor for control, with live attenuated vaccines
      being the most used. However, the apoptotic effect of these vaccines on the bursa
      has not been tested. We determined the apoptotic effect caused by the most used
      vaccines in local production on the bursa of Fabricius cells and the correlation
      with histological changes. In this study, it was demonstrated that apoptosis
      levels in the vaccinated groups were higher than those observed in the non
      vaccinated birds leading to the conclusion that the action of the live virus
      vaccine strains modifies the boundary of the bursa and shapes processes of cell
      death by apoptosis. In contrast to other studies, the vaccine strains used did
      not show the phenomenon of bursal atrophy during the experimental period.

PMID- 28447469
TI  - Two pairs of rare naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione
      derivatives from the red alga Chondria crassicaulis.
AB  - Two pairs of rare naturally occurring racemic lipids, (+/-)-4,7-dihydroxy-4
      methyl-2,5-heptanedione (1), and (+/-)-7-butoxy-4-hydroxy-4-methyl-2,5
      heptanedione (2) were isolated from the red alga Chondria crassicaulis Harv. The
      structures of the racemic mixtures of 1 and 2 were elucidated by detailed
      spectroscopic techniques, including 1D and 2D NMR (1H and 13C NMR, 1H-1H COSY,
      HSQC, and HMBC) as well as mass spectrometry and optical rotation experiments,
      and by comparison with data for related known analogs. This is the first report
      of naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione derivatives.
      Antifungal, PTP1B inhibitory, and receptor tyrosine kinase inhibitory activities
      of these two compounds were investigated. The results showed that compounds 1 and
      2 exhibited good selective inhibition against RET tyrosine kinase activity with
      IC50 values of 9.56 and 8.93 MUM, respectively. Compound 1 also displayed
      moderate antifungal activity against Cryptococcus neoformans (32609), showing a
      MIC80 value of 32 MUg/ml.

PMID- 28447470
TI  - Adapting and developing a video-feedback intervention for co-parents of infants
      at risk of externalising behaviour problems (VIPP-Co): A feasibility study.
AB  - BACKGROUND: Recent research on early interventions with parents of infants at
      risk of externalising behaviour problems indicates that focusing on co-parenting
      and involving fathers in treatment may enhance effectiveness. This article
      reports the development and preliminary evaluation of a brief intervention: video
      feedback intervention to promote positive parenting and sensitive discipline for
      co-parents (VIPP-Co). METHODS: Families who reported to be struggling with their
      infant's behaviour were recruited from the community and received six home-based
      sessions of VIPP-Co. The primary outcome was feasibility of the adapted
      intervention, assessed using semi-structured questionnaires and interviews post
      intervention. Preliminary clinical outcome measures were also recorded. RESULTS:
      In total, five families with infants between 10 and 24 months completed the
      intervention. Feedback data documented high rates of acceptability and
      feasibility. All fathers and mothers completing the intervention reported that it
      positively impacted their understanding of their child's thoughts and feelings,
      as well as their approach to individual parenting and co-parenting. Additional
      preliminary outcome data indicated positive changes in parent-chid interaction
      and a positive trend was found for infant behaviour, parental well-being and
      parent relationship adjustment across the intervention. CONCLUSIONS: The overall
      results of this study are encouraging, but VIPP-Co must be evaluated with larger
      samples to explore its efficacy.

PMID- 28447471
TI  - How does video interaction guidance contribute to infant and parental mental
      health and well-being?
AB  - This article describes the contribution of video interaction guidance (VIG) to
      the development of infant and parental and VIG practitioners' mental health and
      well-being. The theoretical core of VIG was depicted in terms of concepts such as
      intersubjectivity, attunement and mediated learning. The way the VIG principles
      alongside the underpinning values and beliefs promote a process of attunement
      between parent and infant, the VIG practitioner and parent, and the VIG
      practitioner and supervisor is described. This article also describes some of the
      evidence about the effectiveness of video feedback techniques more generally and
      the way in which the underpinning theory of change enables VIG to target key
      ports of entry in terms of areas that have been highlighted by numerous
      epidemiological studies as being important in terms of supporting or derailing
      infant attachment security. A case study is used to demonstrate the way in which
      VIG can be integrated within broader therapeutic approaches such as parent-infant
      psychotherapy to support the interaction of parents who have been deeply
      traumatised in childhood. It also demonstrates how the parallel process of
      practitioner 'attunement' to mother is key to the mother's recovery and her new
      ability to form attuned relationships herself with her children and other adults.

PMID- 28447472
TI  - Four-year reciprocal relationships between personality and functional ability in
      older adults with and without sensory impairment: focus on neuroticism and
      agreeableness.
AB  - OBJECTIVES: Personality traits have been found to influence health and functional
      ability (FA) via multiple pathways. However, personality traits may also change
      in reaction to constraints in FA, particularly in more vulnerable individuals
      with high risk of decline in independent functioning in daily life (e.g. older
      adults with sensory impairment). Therefore, conceptually anchored in the World
      Health Organization's International Classification of Functioning, Disability and
      Health (ICF model), this study investigated reciprocal relationships between
      personality, focusing on neuroticism and agreeableness, and indicators of FA
      (i.e. activities of daily living and subjective autonomy) as well as the
      potentially moderating role of sensory impairment status. METHOD: The study
      sample consisted of 387 older adults (mean age at T1: M = 82.50 years, SD = 4.71
      years) who were either sensory impaired (SI; i.e. visually or hearing impaired)
      or sensory unimpaired (UI). A total of 168 individuals were reassessed four years
      later. RESULTS: Depending on sensory status, personality acted both as predictor
      and as outcome of FA. Neuroticism was more strongly related with later FA
      outcomes in SI than in UI individuals. FA variables, in turn, were significant
      predictors of later neuroticism in UI older adults only and of later
      agreeableness in SI individuals only. CONCLUSION: These findings suggest that the
      late-life personality-FA interplay needs to be considered bidirectional, and the
      direction of associations varies systematically as a function of sensory
      impairment status.

PMID- 28447473
TI  - A Midterm Review of Lesser Toe Arthrodesis With an Intramedullary Implant.
AB  - : Lesser toe deformities are one of the most common conditions encountered by
      podiatric surgeons. When conservative treatments fail surgical correction is
      indicated. Many surgical options have been described to address the complex
      nature of these deformities but no perfect solution has been reported to date.
      However, with the continued advancement of internal fixation technology,
      interphalangeal joint (IPJ) arthrodesis with an intramedullary implant may be a
      good option. This retrospective study presents patient reported outcomes and
      complications at 6 months and 3 years following lesser toe proximal
      interphalangeal joint (PIPJ) arthrodesis with a polyketone intrameduallary
      implant (Toe Grip, Orthosolutions, UK). Between September 2011 and November 2012,
      a total of 38 patients attended for second toe PIPJ arthrodesis by means of the
      Toe Grip device. At 6 months postoperation, 94.7% of patients and at 3 years
      postoperation, 92.8% of patients felt that their original complaint was better or
      much better. Health-related quality of life scores continued to improve overtime
      as measured by the Manchester Oxford Foot Questionnaire. Complications were
      generally observational and asymptomatic. The most common complications were
      floating toes (17.8%), mallet deformities (14.2%), metatarsalgia (17.8%), and
      transverse plane deformity of the toe (10.7%). This study demonstrates excellent
      patient-eported outcomes with minimal symptomatic complications making the "Toe
      Grip" implant a safe and effective alternative fixation device for IPJ
      arthrodesis when dealing with painful digital deformities. LEVELS OF EVIDENCE:
      Therapeutic, Level IV: Case series.

PMID- 28447474
TI  - Erratum.

PMID- 28447475
TI  - Olaratumab for advanced soft tissue sarcoma.
AB  - INTRODUCTION: Olaratumab is a humanized IgG1 monoclonal antibody that blocks the
      platelet-derived growth factor receptor alpha (PDGFRalpha). Its antagonistic
      behavior inhibits the receptor's tyrosine kinase activity, thereby, turning off
      the downstream signaling cascades responsible for soft tissue sarcoma
      tumorigenesis. In October 2016, olaratumab received Food and Drug Administration
      (FDA) approval for its use in combination with doxorubicin for treatment of
      advanced soft tissue sarcoma. Areas covered: This drug profile takes a
      comprehensive look at the clinical studies leading to FDA approval of olaratumab
      as well as its safety and efficacy as a front-line treatment option for sarcoma
      patients. The literature search was primarily conducted using PubMed. Expert
      commentary: The combination of olaratumab plus doxorubicin has provided a new
      front-line therapeutic option for soft tissue sarcoma patients. An open-label
      phase Ib and randomized phase II trial in patients with advanced soft tissue
      sarcoma demonstrated that the addition of olaratumab to doxorubicin prolonged
      progression-free survival by 2.5 months and overall survival by 11.8 months when
      compared to doxorubicin alone. Of importance, this clinically meaningful increase
      in overall survival did not come at the expense of a significantly greater number
      of toxicities. A phase III confirmatory trial (ClinicalTrials.gov Identifier
      NCT02451943) will be completed in 2020.

PMID- 28447477
TI  - Simultaneous Visualization of Hydrogen Peroxide and Water Concentrations Using
      Photofragmentation Laser-Induced Fluorescence.
AB  - A concept based on photofragmentation laser-induced fluorescence (PFLIF) is for
      the first time demonstrated for simultaneous detection of hydrogen peroxide
      (H2O2) and water (H2O) vapor in various mixtures containing the two constituents
      in a bath of argon gas. A photolysis laser pulse at 248 nm dissociates H2O2 into
      OH fragments, whereupon a probe pulse, delayed 100 ns and tuned to an absorption
      line in the A2Sigma+ (v = 1) <- X2Pi(v = 0) band of OH near 282 nm, induces
      fluorescence. The total OH fluorescence reflects the H2O2 concentration, while
      its spectral shape is utilized to determine the H2O concentration via a model
      predicting the ratio between the fluorescence intensities of the A2Sigma+ (v = 1)
      -> X2Pi(v = 1) and the A2Sigma+ (v = 0) -> X2Pi(v = 0) bands. The H2O detection
      scheme requires that the bath gas has a collisional cross-section with OH(A) that
      is significantly lower than that of H2O, which is the case for argon. Spectrally
      dispersed OH fluorescence spectra were recorded for five different H2O2/H2O/Ar
      mixtures; the H2O2 concentration in the range of 30-500 ppm and the H2O
      concentration in the range of 0-3%. Fluorescence intensity ratios predicted by
      the model for these mixtures agree very well with corresponding experimental
      data, which thus validates the model. The concept was also demonstrated for two
      dimensional imaging, using two intensified charge-coupled device (CCD) cameras
      for signal detection. Water content was here sensed through the different
      temporal characteristics of the two fluorescence bands by triggering the two
      cameras so that one captures the total OH fluorescence while the other one
      captures only the early part, which mainly stems from A2Sigma+ (v = 1) -> X2Pi(v
      = 1) fluorescence. Hence, the H2O2 concentration is reflected by the image of the
      camera recording the total OH fluorescence, whereas H2O concentration is
      extracted from the ratio between the two camera images. Quantification of the
      concentrations was carried out based on calibration measurements performed in
      known mixtures of H2O2 (30-500 ppm) and H2O (0-3%) in bulk argon. The detection
      limits for single-shot imaging are estimated to be 20 ppm for H2O2 and 0.05% for
      H2O. The authors believe that the concept provides a valuable asset in, for
      example, pharmaceutical or aseptic food packaging applications, where H2O2/H2O
      vapor is routinely used for sterilization.

PMID- 28447476
TI  - MTBVAC from discovery to clinical trials in tuberculosis-endemic countries.
AB  - INTRODUCTION: BCG remains the only vaccine against tuberculosis (TB) in use today
      and despite its impressive global coverage, the nature of BCG protection against
      the pulmonary forms of TB remains subject to ongoing debate. Because of the
      limitations of BCG, novel TB vaccine candidates have been developed and several
      have reached the clinical pipeline. One of these candidates is MTBVAC, the first
      and only TB vaccine in the clinical pipeline to date based on live-attenuated
      Mycobacterium tuberculosis that has successfully entered clinical evaluation, a
      historic milestone in human vaccinology. Areas covered: This review describes
      development of MTBVAC from discovery to clinical development in high burden TB
      endemic countries. The preclinical experiments where MTBVAC has shown to confer
      improved safety and efficacy over BCG are presented and the clinical development
      plans for MTBVAC are revealed. The search of all supportive literature in this
      manuscript was carried out via Pubmed. Expert commentary: Small experimental
      medicine trials in humans and preclinical efficacy studies with a strong
      immunological component mimicking clinical trial design are considered essential
      by the scientific community to help identify reliable vaccine-specific correlates
      of protection in order to support and accelerate community-wide efficacy trials
      of new TB vaccines.

PMID- 28447478
TI  - Pulsatile kisspeptin effectively stimulates gonadotropin-releasing hormone (GnRH)
      producing neurons.
AB  - Hypothalamic kisspeptin is integral to the hypothalamic-pituitary-gonadal axis by
      stimulating gonadotropin-releasing hormone (GnRH) release. GnRH is released from
      the hypothalamus in a pulsatile manner and determines the output of the
      gonadotropins. However, the effect of kisspeptin on GnRH-secreting cells remains
      unknown. In an experiment using static cultures of GT1-7 cells, kisspeptin did
      not significantly increase GnRH mRNA expression. However, when kisspeptin was
      administered to the cells in a pulsatile manner, GnRH mRNA expression was
      significantly increased. Primary cultures of fetal rat brain containing GnRH
      expressing neurons responded to kisspeptin and increased GnRH mRNA expression by
      1.65 +/- 0.27-fold in the static condition. When cells were stimulated with
      kisspeptin in a pulsatile manner, GnRH mRNA expression was increased by up to
      2.40 +/- 0.21-fold. In perifused GT1-7 cells, pulsatile, but not continuous
      kisspeptin stimulation, effectively stimulated GnRH mRNA expression. To assess
      the level of stimulation of GnRH neurons by kisspeptin, the expression of c-fos
      was examined. In GT1-7 cells, kisspeptin stimulation in the static condition
      failed to increase c-fos mRNA expression. However, pulsatile kisspeptin
      stimulation increased c-fos mRNA by 2.31 +/- 0.47-fold. Similar to the phenomenon
      observed in GT1-7 cells, pulsatile, but not static, kisspeptin stimulation
      significantly increased c-fos mRNA expression in the primary cultures of fetal
      rat brain. These observations suggest that pulsatile kisspeptin more effectively
      stimulates GnRH-producing cells to increase the production of GnRH.

PMID- 28447479
TI  - Autotaxin inhibitors: a patent review (2012-2016).
AB  - INTRODUCTION: Autotaxin (ATX) is a secreted enzyme that hydrolyzes
      lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline. The ATX/LPA
      axis has received increasing interest in recent years because both the enzyme ATX
      and the bioactive lipid LPA are involved in various pathological conditions such
      as tumor progression and metastasis, fibrotic diseases, autoimmune diseases,
      arthritis, chronic hepatitis, obesity and impaired glucose homeostasis. Thus, a
      great effort has been devotd in developing synthetic ATX inhibitors as new agents
      to treat various diseases including cancer and fibrotic diseases. Areas covered:
      This review article summarizes the autotaxin inhibitors presented in patent
      literature from October 2012 to August 2016 and their biological evaluation,
      discussing their activities in vitro and in vivo. Expert opinion: During the
      recent years, there has been an intensive effort on the discovery of potent and
      selective ATX inhibitors. Although various synthetic inhibitors have been
      developed, only limited studies for their in vivo activity have been reported so
      far. A decade after the first claim of synthetic ATX inhibitors in 2006, one
      inhibitor has been in clinical trials for idiopapthic pulmonary fibrosis. The use
      of ATX inhibitors seems an attractive strategy to produce novel medicinal agents,
      for example anticancer agents.

PMID- 28447480
TI  - Predictive and explanatory factors of cardiovascular disease in people with
      adequately controlled type 2 diabetes.
AB  - Aims To explore the predictive and explanatory factors on the incidence of
      cardiovascular disease and the impact of visit-to-visit variability (VVV) of risk
      factors on incident cardiovascular disease in people with type 2 diabetes with no
      history of prior cardiovascular disease. Methods We performed a historical cohort
      study (2008-2011) on 481 people with type 2 diabetes and no history of
      cardiovascular disease. Cardiovascular risk factors were assessed at baseline and
      repeatedly during follow-up. The predictive analysis included the variables at
      enrollment, and explanatory analyses were based on mean of the variables measured
      repeatedly. VVV of the main variables was measured using the standard deviation
      and coefficient of variation of the measured variables. Separate multivariate
      binary logistic models were constructed for each parameter with the incident
      cardiovascular disease. Results Mean age of the participants was 54.9 years, mean
      glycated hemoglobin was 56 mmol/mol, and mean blood pressure was 125/78 mmHg.
      Incident cardiovascular disease developed in 14.3% of the participants. The 2-h
      post breakfast blood glucose was associated with incident cardiovascular disease
      (odds ratio 1.44; confidence interval = 1.08-1.90; p = 0.01). For each 1 mmol/l
      increase in postprandial glucose there was a 44% increase in risk of incident
      cardiovascular disease. VVV of glycemic indices, blood pressure, lipids, body
      mass index and creatinine were not associated with occurrence of cardiovascular
      events. Conclusion In this population of patients with type 2 diabetes and no
      history of cardiovascular disease in whom other cardiovascular risk factors are
      within or near to the recommended targets, 2-h post breakfast blood glucose level
      is associated with incident cardiovascular disease.

PMID- 28447481
TI  - A Correction Method for Attenuated Total Reflection-Far Ultraviolet Spectra Via
      the Use of Charge Transfer to Solvent Band Intensities of Iodide in the
      Ultraviolet Region.
AB  - Attenuated total reflection (ATR) spectra, which are often used in IR analysis,
      can be transformed into extinction and refraction spectra by Kramers-Kronig
      transformation (KKT) with Fresnel equations. However, it is often difficult to
      obtain correct optical indices due to the inherent instrumental functions. This
      paper proposes a simple practical method for correction of KKT with two
      parameters, which include all the effects of the instrumental function. In order
      to obtain the parameters of the instrumental function, absorption ratios of
      charge transfer to solvent (CTTS) transitions of aqueous iodide ions observed at
      195 nm and 230 nm were used as a standard. The absorption indices calculated from
      the ATR spectra with the parameters correspond reasonably well to those given by
      the transmittance spectra not only in the UV region but also in the far
      ultraviolet (FUV, 120-200 nm) region. By applying the corrected KKT to the ATR
      FUV spectra of aqueous potassium halide solutions in the range of 0-2 M, correct
      features of the absorption spectra of KCl and KBr, whose CTTS bands are thought
      to be observed in FUV region, were confirmed. It is possible to use the
      parameters representing the instrument function as long as the instrument is not
      changed.

PMID- 28447482
TI  - Quantitative Potassium Measurements with Laser-Induced Breakdown Spectroscopy
      Using Low-Energy Lasers: Application to In Situ K-Ar Geochronology for Planetary
      Exploration.
AB  - In situ radiogenic isotope measurements to obtain the absolute age of geologic
      events on planets are of great scientific value. In particular, K-Ar isochrons
      are useful because of their relatively high technical readiness and high
      accuracy. Because this isochron method involves spot-by-spot K measurements using
      laser-induced breakdown spectroscopy (LIBS) and simultaneous Ar measurements with
      mass spectrometry, LIBS measurements are conducted under a high vacuum condition
      in which emission intensity decreases significantly. Furthermore, using a laser
      power used in previous planetary missions is preferable to examine the technical
      feasibility of this approach. However, there have been few LIBS measurements for
      K under such conditions. In this study, we measured K contents in rock samples
      using 30 mJ and 15 mJ energy lasers under a vacuum condition (10-3 Pa) to assess
      the feasibility of in situ K-Ar dating with lasers comparable to those used in
      NASA's Curiosity and Mars 2020 missions. We obtained various calibration curves
      for K using internal normalization with the oxygen line at 777 nm and continuum
      emission from the laser-induced plasma. Experimental results indicate that when
      K2O < 1.1 wt%, a calibration curve using the intensity of the K emission line at
      769 nm normalized with that of the oxygen line yields the best results for the 30
      mJ laser energy, with a detection limit of 88 ppm and 20% of error at 2400 ppm of
      K2O. Futhermore, the calibration curve based on the K 769 nm line intensity
      normalized with continuum emission yielded the best result for the 15 mJ laser,
      giving a detection limit of 140 ppm and 20% error at 3400 ppm K2O. Error
      assessments using obtained calibration models indicate that a 4 Ga rock with 3000
      ppm K2O would be measured with 8% (30 mJ) and 10% (15 mJ) of precision in age
      when combined with mass spectrometry of 40Ar with 10% of uncertainty. These
      results strongly suggest that high precision in situ isochron K-Ar dating is
      feasible with a laser used in previous and upcoming Mars rover missions.

PMID- 28447483
TI  - The role of adhesions between homologous cancer cells in tumor progression and
      targeted therapy.
AB  - INTRODUCTION: Adhesions between homologous cancer cells play an important role in
      promoting tumor progression and designing tumor-targeting methods. Known as
      'homologous adhesions' of cancerous cells, these are usually more specific than
      adhesions to normal cells and heterogenic cells, and they have been widely
      discovered both in vivo and in vitro. The aberrant expression of cell adhesion
      related molecules (CARMs) on each species of cancer cells is mainly responsible
      for inducing more specific homologous adhesions. Based on the improvement of
      biomimetic technologies, such adhesion has been investigated and applied deeply
      in drug delivery systems recently. Areas covered: This review focuses on the
      discovery, mechanism and application of homologous adhesion and aims to assist
      researchers with a clear understanding for more effective development. The
      advantages and challenges of recent research progress and therapeutic
      applications are also described and discussed. Expert commentary: Homologous
      adhesion shows promise in providing new strategies for targeted drug delivery and
      tailored cancer treatments. However, the 'homing' property of certain cancer cell
      types remains unclear and needs to be further defined.

PMID- 28447484
TI  - Assessment of pain during medical abortion with home use of misoprostol.
AB  - OBJECTIVES: Although medical abortion with home use of misoprostol has been shown
      to be safe and acceptable, there are few data about the experience of pain during
      the procedure. The aims of this study were to assess the intensity of pain
      associated with home use of misoprostol for medical abortion and to identify
      variables associated with severe pain. METHODS: This was an observational study
      using an anonymous web-based questionnaire in patients having a medical abortion
      at home in France between 1 December 2013 and 30 April 2014. RESULTS: The
      questionnaire was completed by 232 women and the results of 193 were retained for
      analysis. The average pain score was 5.6 on a 10 point scale. A pain score >=6
      was rated as severe and was reported by 105 patients (54%). Nulliparity (odds
      ratio [OR] 4.10; 95% confidence interval [CI] 2.04, 8.22; p < .0001), lack of
      choice regarding the method of abortion (OR 2.32; 95% CI 1.13, 4.78; p = .0218)
      and lack of information about the level of pain associated with the procedure (OR
      3.27; 95% CI 1.09, 9.74; p = .0334) were significantly correlated with severe
      pain. Analgesic prescriptions were very heterogeneous. CONCLUSIONS: Pain remains
      the main side effect of medical abortion. More studies are needed on pain
      assessment and the effectiveness of analgesic treatments in women using
      misoprostol at home for medical abortion, in order to improve their care and
      improve evidence-based guidelines.

PMID- 28447485
TI  - Empirical estimation of under-reporting in the U.S. Food and Drug Administration
      Adverse Event Reporting System (FAERS).
AB  - BACKGROUND: To examine how closely reporting rates in the FDA Adverse Event
      Reporting System (FAERS) reflect expected rates of known adverse drug events
      (ADEs). METHODS: We selected three groups of drugs to reflect hypothesized
      variation in sensitivity to reporting, including statins, biologics, and narrow
      therapeutics index drugs (NTI). The numbers of ADEs in FAERS were divided by
      utilization estimates from ambulatory health care data (NAMCS/NHAMCS) to
      calculate a reported proportion. One sample z-test for proportions compared the
      proportion of ADEs reported to an expected ADE proportion derived from drug
      labels, reference databases, and peer-reviewed papers. RESULTS: The majority of
      drug-ADE pairs showed significant under-reporting. For example, roughly 0.01% to
      44% of statin events were reported (z-test p < 0.0001). Biological (0.002% to
      >100%) and NTI (20% to >100%) drugs had relatively higher reporting rates.
      Roughly 20% to 33% of the minimum number of expected serious events were reported
      with biologics and NTI drugs. CONCLUSIONS: This study supports previous evidence
      of under-reporting of ADEs in spontaneous reporting data. But, under-reporting
      varies considerably by the type of drug and the type of ADEs, and this
      variability in under-reporting should be considered when interpreting safety
      signals.

PMID- 28447486
TI  - Guidance to develop individual dose recommendations for patients on chronic
      hemodialysis.
AB  - INTRODUCTION: In addition to tailored clinical trials in patients on chronic
      hemodialysis (HD) during drug development, clinician-initiated post-marketing
      studies and case reports on individual pharmacokinetic (PK) assessments provide
      an important source of information about drug dialysability and individualized
      dose recommendations in this vulnerable population. Areas covered: First, factors
      that may alter drug exposure in HD patients are explained. Second, available
      regulatory and methodological guidelines for PK assessments in this population
      are summarized. Third, a 4-step approach is proposed to develop individual dose
      recommendations for HD patients receiving drugs without data from a PK study: (1)
      literature search, (2) model-based dosage decisions, (3) validation and
      refinement through concentration monitoring, and (4) publication of relevant
      observations. Fourth, clinician-initiated PK assessments and case reports to
      evaluate and individualize use of drugs in HD patients are reviewed, and
      recommendations to enhance their quality are discussed. Expert commentary:
      Guidance on collecting and reporting PK information in individual HD patients is
      warranted to ensure completeness and consistency of such PK studies. A checklist
      and template for easy-to-implement PK calculations and pharmacometric modeling is
      provided to facilitate evaluation and individualization of dosing strategies in
      these patients.

PMID- 28447487
TI  - Tissue engineered vascular grafts: current state of the field.
AB  - INTRODUCTION: Conventional synthetic vascular grafts are limited by the inability
      to remodel, as well as issues of patency at smaller diameters. Tissue-engineered
      vascular grafts (TEVGs), constructed from biologically active cells and
      biodegradable scaffolds have the potential to overcome these limitations, and
      provide growth capacity and self-repair. Areas covered: This article outlines the
      TEVG design, biodegradable scaffolds, TEVG fabrication methods, cell seeding,
      drug delivery, strategies to reduce wait times, clinical trials, as well as a 5
      year view with expert commentary. Expert commentary: TEVG technology has
      progressed significantly with advances in scaffold material and design, graft
      design, cell seeding and drug delivery. Strategies have been put in place to
      reduce wait times and improve 'off-the-shelf' capability of TEVGs. More recently,
      clinical trials have been conducted to investigate the clinical applications of
      TEVGs.

PMID- 28447488
TI  - Observation of the 162Dy-164Dy Isotope Shift for the 0 -> 16 717.79 cm-1 Optical
      Transition.
AB  - In this work, we report a newly observed isotope shift between 162Dy and 164Dy
      isotopes for the 0 -> 16 717.79 cm-1 (598.003 nm) optical transition. We compared
      the newly observed results against two other lines (597.452 nm and 598.859 nm),
      which we measured in this work, and were already reported in the literature. The
      newly observed 162-164 Dy isotope shift, shows at least a 20% larger isotope
      shift than the isotope shifts for the other two lines investigated. The larger
      162-164 isotope shift observed for the 598.003 nm line could lead to an increased
      isotope selectivity for atomic vapor laser isotope separation (AVLIS). Hence,
      this line could be a good choice for application in AVLIS. Experimental data
      available in the literature for the 597.452 nm and 598.859 nm lines, enabled us
      to perform simulations of spectra for both lines, in order to confirm the
      accuracy of our experimental measurements.

PMID- 28447489
TI  - Forodesine in the treatment of cutaneous T-cell lymphoma.
AB  - INTRODUCTION: Cutaneous T-cell lymphoma (CTCL) is characterized by the
      accumulation of neoplastic CD4+ T lymphocytes in the skin. Given the lack of
      curative treatments for CTCL, there is a significant need for new, superior
      therapies. Forodesine is a transition-state analogue that inhibits purine
      nucleoside phosphorylase. Because it selectively targets T lymphocytes, it
      represents a drug of interest for the treatment of CTCL. Areas covered: Phase
      I/II dose-ranging studies of intravenous (IV) and oral forodesine demonstrated
      its activity, safety, and tolerability for refractory CTCL. Response rates were
      31% and 27%, respectively. No dose-limiting toxicities were observed. These
      studies were followed by a phase II trial of oral forodesine 200 mg daily. This
      oral formulation showed only partial activity, with a response rate of 11%,
      likely attributable to underdosing. Common adverse events in these trials
      included infection, fatigue, peripheral edema, nausea, pruritus, headache, and
      insomnia. Expert opinion: IV and oral formulations of forodesine have
      demonstrated partial activity and an acceptable safety profile in patients with
      refractory CTCL. A higher oral dose, or sequential therapy consisting of IV
      forodesine followed by maintenance oral forodesine, may be more effective. With
      proper dosing, forodesine may emerge as a safe and effective treatment for
      refractory CTCL.

PMID- 28447490
TI  - Risks and benefits of pre-operative dexmedetomidine in oral and maxillofacial
      surgeries: a systematic review.
AB  - INTRODUCTION: Oral and maxillofacial surgeries might induce anxiety and pain to
      the patients. Sedative agents are one of the best ways for eliminating such
      consequences. Dexmedetomidine (DEX) is a recent sedative agent which presents
      higher sedative quality with greater specificity than other drugs. The aim of
      present paper is to evaluate the risks and benefits of administrating DEX during
      oral and maxillofacial surgeries by reviewing high quality released articles.
      Areas covered: Searches on PubMed, Scopus and Web of Science databases were
      completed with focus on randomized controlled trials (RCT). Related articles,
      from 2000 to 2015, were selected based on inclusion criteria and quality
      assessments factors. Full texts of the selected articles were screened and their
      significant information were gathered for judgments. Expert opinion: 17 RCTs on a
      total of 765 patients were screened. Some of the difficulties during reviewing
      the articles were: different pharmacokinetic and pharmacodynamics of drugs when
      combined with DEX, different time spots and method of monitoring, including
      studies on both minor and major surgeries for better data collection. Recent
      researches are going to focus on application of DEX for in-office procedures
      because of its desirable properties. Nevertheless, the analgesic and amnesic
      features of DEX are still questionable.

PMID- 28447491
TI  - Mobile communication jacket for people with severe speech impairment.
AB  - PURPOSE: Cerebral palsy is a movement disorder caused by damage to motor control
      areas of the developing brain during early childhood. Motor disorders can also
      affect the ability to produce clear speech and to communicate. The aim of this
      study was to develop and to test a prototype of an assistive tool with an
      embedded mobile communication device to support patients with severe speech
      impairments. METHODS: A prototype was developed by equipping a cycling jacket
      with a display, a small keyboard, a LED and an alarm system, all controlled by a
      microcontroller. Functionality of the prototype was tested in six participants
      (aged 7-20 years) with cerebral palsy and global developmental disorder and three
      healthy persons. A patient questionnaire consisting of seven items was used as an
      evaluation tool. RESULTS: A working prototype of the communication jacket was
      developed and tested. The questionnaire elicited positive responses from
      participants. Improvements to correct revealed weaknesses were proposed.
      Enhancements like voice output of pre-selected phrases and enlarged display were
      implemented. CONCLUSIONS: Integration in a jacket makes the system mobile and
      continuously available to the user. The communication jacket may be of great
      benefit to patients with motor and speech impairments. Implications for
      Rehabilitation The communication jacket developed can be easily used by people
      with movement and speech impairment. All technical components are integrated in a
      garment and do not have to be held with the hands or transported separately. The
      system is adaptable to individual use. Both expected and unexpected events can be
      dealt with, which contributes to the quality of life and self-fulfilment.

PMID- 28447492
TI  - Statistical Aspects of Near-Infrared Spectroscopy for the Characterization of
      Errors and Model Building.
AB  - Due to the complex nature of near-infrared (NIR) spectra, it is usually very
      difficult to provide quantitative interpretations of spectral data. As a
      consequence, careful building and validation of calibration models are of
      fundamental importance prior to development of useful applications of NIR
      technologies. For this reason, this work presents a statistical study about the
      NIR spectroscopy, analyzing the NIR behavior when the experimental conditions are
      changed. Near-infrared spectra were measured at different temperatures and
      stirring velocities for systems containing a pure solvent and a suspension of
      polymer powder in order to perform the error analysis. Then, mixtures of xylene
      and toluene were analyzed through NIR at different temperatures and stirring
      velocities and the obtained data were used to build calibration models with
      multivariate techniques. The results showed that the precision of the NIR
      measurements depends on the analytical conditions and that unavoidable
      fluctuations of spectral data (or spectral data variability) are strongly
      correlated, leading to full covariance matrices of spectral fluctuations, which
      has been surprisingly neglected during quantitative analyses. In particular,
      modeling of the xylene/toluene NIR data performed with different multivariate
      techniques revealed that the principal directions are not preserved when the real
      covariance matrix of measurement errors is taken into account.

PMID- 28447493
TI  - M2 segment dissection of middle cerebral artery diagnosed using high-resolution
      magnetic resonance imaging.
AB  - Middle cerebral artery (MCA) dissection is a rare cause of ischemic stroke,
      especially in the M2 or M3 segments. Diagnosis of intracranial artery dissection
      remains challenging. We herein report a case of M2 segment dissection of the MCA
      with typical features of an intimal flap and intramural hematoma diagnosed using
      high-resolution 3T magnetic resonance imaging. This imaging technique might be a
      more effective noninvasive method by which to diagnose M2 segment dissection of
      the MCA than either computed tomography angiography or digital subtraction
      angiography.

PMID- 28447494
TI  - Subtotal resection of vestibular schwannoma: Evaluation with Ki-67 measurement,
      magnetic resonance imaging, and long-term observation.
AB  - Purpose The aim of this study was to compare the postoperative clinical and
      radiological data of patients with vestibular schwannomas who were initially
      managed by near total resection (NTR) or subtotal resection (STR). The Ki-67
      analysis results were compared with tumor regrowth to determine the presence of a
      correlation between this proliferative index and postoperative tumor regrowth.
      Study Design Seventeen adult patients (7 male, 10 female) were retrospectively
      reviewed. Nine (52.9%) and eight (47.1%) patients underwent NTR and STR,
      respectively. Postoperative clinical and radiological data associated with
      vestibular schwannoma growth were compared with the Ki-67 immunohistochemical
      analysis results. Results Evidence of clinically significant regrowth was
      observed in four (23.5%) patients. Patients who underwent NTR had a lower
      rate/incidence of tumor regrowth than did patients who underwent STR. Patients
      with a higher Ki-67 index had the highest tumor regrowth rates. Conclusions Our
      study indicates that assessment of the Ki-67 index may be useful for determining
      the probability of regrowth of vestibular schwannomas when only partial removal
      is accomplished.

PMID- 28447495
TI  - Quality of life of patients after total laryngectomy: the struggle against
      stigmatization and social exclusion using speech synthesis.
AB  - In this article, we deal with the problem of potential stigmatization and social
      exclusion of people that have voice/speech problems due to neck cancer,
      especially those who have lost their voice because of total laryngectomy, and we
      analyze how this potential stigmatization could be alleviated by personalized
      speech synthesis. We used a mixed-method approach, consisting of quality of life
      questionnaires and in-depth semi-structured interviews, in order to provide more
      generalizable as well as rich information. We found out that people with speech
      problems feel depressed because of their health status and anxiety during social
      interactions, as they think that other people perceive them as abnormal, or they
      directly experience symbolic violence. For overcoming these negative feelings,
      the crucial factors are family relationships and maintaining employment. In both
      factors, speech synthesis can help significantly. Implications for rehabilitation
      Personalized speech synthesis can help considerably to people with severe voice
      impairment in their (re)integration into society. Where possible and appropriate,
      personalized speech synthesis should be offered as an option to "traditional"
      voice substitutions.

PMID- 28447498
TI  - Regulating vaccines at the FDA: development and licensure of Zika vaccines.

PMID- 28447499
TI  - Is pre-implantation genetic diagnosis (PGD) more of a strain regarding
      satisfaction with marital quality for male or female partners? A three-year
      follow-up study.
AB  - INTRODUCTION: Men and women with a hereditary genetic disease are faced with
      different options when they plan to become parents. One is pre-implantation
      genetic diagnosis (PGD) which is a combination of in vitro fertilization (IVF)
      and genetic analysis of the embryo before implantation. The present study focuses
      on how men and women planning for PGD experience the quality of marital
      satisfaction when they apply for treatment and again, three years later. METHODS:
      The study was a prospective cohort study where all couples (n = 22) applying for
      PGD during 2010 and 2011 were eligible. Nineteen women and 17 men (i.e. 17
      couples and two women) participated. Participants answered several questionnaires
      (Dyadic Adjustment Scale, Hospital Anxiety and Depression Scale and Parental
      Stress Questionnaire) before PGD treatment, and again three years later. RESULTS:
      Women who underwent PGD rated the quality of their marital relationship similarly
      to that of first-time parents and IVF couples, whereas men rated the marital
      quality somewhat lower than the contrasts groups. Satisfaction with marital
      quality was stable over the three-year period although men were less satisfied
      than women on both occasions. At year three, there was a significant correlation
      between martial satisfaction and parental stress in men, and between martial
      satisfaction and anxiety and depression in women. DISCUSSION: Men are equally, or
      more, affected by their situation than their female partners, with consequences
      for satisfaction with marital quality. For this reason they should be included in
      any counselling offered.

PMID- 28447500
TI  - Young Skilled Deaf Readers Have an Enhanced Perceptual Span in Reading.
AB  - Recently, Belanger, Slattery, Mayberry and Rayner (2012) showed, using the moving
      window paradigm, that profoundly deaf adults have a wider perceptual span during
      reading relative to hearing adults matched on reading level. This difference
      might be related to the fact that deaf adults allocate more visual attention to
      simple stimuli in the parafovea (Bavelier, Dye & Hauser, 2006). Importantly, this
      reorganization of visual attention in deaf individuals is already manifesting in
      deaf children (Dye, Hauser & Bavelier, 2009). This leads to questions about the
      time course of the emergence of an enhanced perceptual span (which is under
      attentional control; Rayner, 2014; Miellet, O'Donnell, & Sereno, 2009) in young
      deaf readers. The present research addressed this question by comparing the
      perceptual spans of young deaf readers (age 7-15) and young hearing children (age
      7-15). Young deaf readers, like deaf adults, were found to have a wider
      perceptual span relative to their hearing peers matched on reading level,
      suggesting that strong and early reorganization of visual attention in deaf
      individuals goes beyond the processing of simple visual stimuli and emerges into
      more cognitively complex tasks, such as reading.

PMID- 28447501
TI  - Imaging Acute and Chronic Pain in the Human Brainstem and Spinal Cord.
AB  - While acute pain serves as a protective mechanism designed to warn an individual
      of potential or actual damaging stimuli, chronic pain provides no benefit and is
      now considered a disease in its own right. Since the advent of human brain
      imaging techniques, many investigations that have explored the central
      representation of acute and chronic pain have focused on changes in higher order
      brain regions. In contrast, far fewer have explored brainstem and spinal cord
      function, mainly due to significant technical difficulties. In this review, we
      present some of the recent human brain imaging studies that have specifically
      explored brainstem and spinal cord function during acute noxious stimuli and in
      individuals with chronic pain. We focus particularly on investigations that
      explore changes in areas that receive nociceptor afferents and compare humans and
      experimental animal data in an attempt to describe both microscopic and
      macroscopic changes associated with acute and chronic pain.

PMID- 28447502
TI  - The effect of endometrial injury on implantation and clinical pregnancy rates.
AB  - AIM: To assess the effect of endometrial scratching (ES) on in vitro
      fertilization-embryo transfer outcome (IVF-ET) Materials and methods:
      Retrospective matched case control study including all fresh IVF cycles performed
      between January 2006 and December 2012 at an academic IVF center. ES with an
      endometrial biopsy catheter was performed in the cycle preceding the index IVF
      cycle. Patients (n = 238) were pair matched with controls according to age,
      number of previous failed IVF cycles and number of embryos transferred. RESULTS:
      Demographic and cycle characteristics were comparable in all of the following:
      age, number of previous cycles, number of collected oocyte, number of embryos
      transferred and quality of transferred embryos. Implantation, clinical and
      ongoing pregnancy rates were comparable in both groups (28%, 34% and 18.4% vs
      30%, 40.3% and 29%, in ES group and controls, respectively). Logistic regression
      analysis found no significant association between ES and pregnancy rate.
      CONCLUSIONS: Mechanical endometrial stimulation did not improve implantation and
      pregnancy rates. Furthermore, no factors that may predict which patients could
      benefit from ES were identified. Further prospective studies are warranted to
      evaluate possible benefits in different subsets of patients such as patients with
      recurrent implantation failures.

PMID- 28447503
TI  - 1,6-O,O-Diacetylbritannilactone suppresses activation of mast cell and airway
      hyper-responsiveness.
AB  - Mast cells play critical roles in allergic disorders such as atopic dermatitis
      and allergic asthma. The aim of this study was to investigate the anti
      inflammatory and anti-asthmatic activities of 1,6-O,O-diacetylbritannilactone
      (OODBL) isolated from Inula japonica Thunb. (I. japonica) in a murine asthma
      model and bone marrow-derived mast cells (BMMCs). In an ovalbumin-induced asthma
      model, OODBL administration attenuated the airway hyper-responsiveness induced by
      aerosolized methacholine and serum IgE level in asthmatic mice. In vitro system,
      we found that OODBL reduced leukotriene C4 production and degranulation through
      the suppression of cytosolic phospholipase A2 phosphorylation and phospholipase
      Cgamma-mediated Ca2+ influx in IgE/antigen-stimulated BMMCs. Taken together,
      OODBL may have therapeutic potential in the treatment of allergic diseases such
      as asthma.

PMID- 28447504
TI  - Placental growth factor (PlGF) as an angiogenic/inflammatory switcher: lesson
      from early pregnancy losses.
AB  - Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular
      endothelial growth factor (VEGF) family. In addition to the angiogenic function
      of PlGF, in some conditions such as preeclampsia and early pregnancy losses, it
      can induce inflammatory reactions which could be accompanied with reduced
      angiogenesis. Hence, it is crucial to investigate inflammatory and angiogenic
      switching states and understand underlying mechanisms. PlGF is expressed in
      endometrium, placenta and trophoblast cells and is involved in maturation of
      uterine NK cells. Up-regulation of PlGF directs VEGF to VEGFR-2 and reinforces
      angiogenesis. However, when VEGF/VEGFR-2 signaling pathway is impaired, PlGF may
      shift to severe inflammation and cause tissue damages which could lead to early
      pregnancy losses. Downregulation of PlGF has also been reported in pregnancy
      complications. In this review, we discussed the role of PlGF in embryo
      implantation failure and early pregnancy loss and also possible mechanisms
      regarding the role of PlGF in angiogenic/inflammatory switching in early
      pregnancy losses. Furthermore, we summarized the effects of various compounds on
      PlGF expression and briefly talked about its therapeutic potential that may be an
      opportunity for prevention of pregnancy loss.

PMID- 28447505
TI  - Does pituitary suppression affect live birth rate in women with congenital
      hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A
      multicenter cohort study.
AB  - In this retrospective multicenter cohort study, women with congenital
      hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic
      sperm injection in-between 2010-2014 were compared to age-matched controls with
      tubal factor infertility (n = 114) to assess ovarian stimulation cycle and
      pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6%
      in CHH and controls groups, respectively (p = 0.36). Comparable success rates
      were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78
      2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the
      gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH
      agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25
      cases. Compared to women with PS, women without PS had significantly higher
      embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a
      trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of
      statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and
      miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women
      who were given estrogen + progesterone and progesterone alone to support the
      luteal phase. In conclusion, the optimal stimulation protocol appears to be
      exogenous gonadotropin stimulation alone, without PS, and progesterone-only
      luteal phase support in CHH patients.

PMID- 28447506
TI  - Anti-inflammatory and gastroprotective potential of leaf essential oil of
      Cinnamomum glanduliferum in ethanol-induced rat experimental gastritis.
AB  - CONTEXT: Nothing could be found in the literature concerning Cinnamomum
      glanduliferum (Wall) Meissn (Lauraceae) bark (CG) in Egypt. OBJECTIVE: To
      investigate CG volatile oil chemically and its anti-inflammatory and
      gastroprotective effects. MATERIALS AND METHODS: Essential oils were investigated
      by GC-MS. Leaves oil was assessed at doses of 250, 500 and 1000 mg/kg for its
      anti-inflammatory effect against carrageenan-induced rat oedema model. Serum
      inflammation markers were measured. The gastro-protective effect of the same
      doses of the volatile oil was also tested in ethanol-induced non-ulcerative
      gastritis model in rats. Stomach oxidative stress markers were examined following
      1 h after intragastric ethanol administration. RESULTS: Twenty-five and 20
      compounds were identified from leaf and branch oils, respectively (98.85 and
      99.13%). The major ones were: eucalyptol (59.44%; 55.74%), sabinene (14.99%;
      7.12%), alpha-terpineol (6.44%; 9.81%), alpha-pinene (5.27%; 4.71%). Following 4
      h of treatment leaves volatile oil at doses of 250, 500 and 1000 mg/kg
      significantly reduced paw volume to 94, 82 and 69%, respectively. The same doses
      significantly reduced COX-2 activity to 73.8, 50.7 and 21.4 nmol/min/mL,
      respectively. A significant reduction of PGE2 concentration was observed (2.95 +/
      0.2, 2.45 +/- 0.15 and 1.75 +/- 0.015 pg/mL). CG oil exhibited a significant
      modulatory effect on ethanol-induced gastritis in rats as the level of NO reduced
      to 32, 37 and 41 MUM nitrate/g and also a significant inhibition of lipid
      peroxidation was observed via reduction of MDA concentration (1.15, 1.11 and 1.04
      nmol/g). CONCLUSION: CG volatile oil exhibited an anti-inflammatory effect and
      protected against ethanol-induced non-ulcerative gastritis.

PMID- 28447507
TI  - Akinetic mutism reversibility after L-dopa therapy in unilateral left anterior
      cerebral artery infarction.

PMID- 28447510
TI  - Genomics and World Health.

PMID- 28447512
TI  - Centella asiatica enhances hepatic antioxidant status and regulates hepatic
      inflammatory cytokines in type 2 diabetic rats.
AB  - CONTEXT: Neutralizing the over-activation of oxidative stress and inflammation
      remains an important goal in the management of type 2 diabetes mellitus (T2DM).
      Centella asiatica (L.) Urban (Apiaceae) (CA) has been used in traditional
      folklore in Africa and Asia to treat various ailments including diabetes.
      OBJECTIVE: We investigated the hepatic antioxidant and anti-inflammatory
      potential of methanol extract of CA leaves in T2DM. MATERIALS AND METHODS: T2DM
      was induced in male Sprague-Dawley rats with 10% fructose in drinking water for
      14 days followed by a single intraperitoneal injection of streptozotocin (40
      mg/kg b.wt). Hepatic oxidant/antioxidant status was assessed by measuring the
      concentrations of malondialdehyde (MDA), ferric reducing antioxidant power
      (FRAP), oxygen radical absorbance capacity (ORAC), Trolox equivalent antioxidant
      capacity (TEAC), reduced glutathione (GSH) and activities of glutathione S
      transferase (GST) and glutathione peroxidase (GPX). The concentrations of
      cytokines IL-1beta, IL-4, IL-6, IL-10, MCP-1 and TNF-alpha in the liver were
      determined. RESULTS: Diabetes increased MDA formed (47%) and reduced FRAP (20%),
      TEAC (15%), GSH levels (32%), significantly; decreased GST and GPX activities in
      the liver and elevated levels of cytokines studied. Treatment of diabetic rats
      with 500 mg/kg b.wt CA for 14 days decreased MDA (44%); elevated FRAP (15%) and
      GSH (131%) levels and increased the activities of GST and GPX by 16%. Hepatic
      concentrations of IL-1beta, MCP-1 and TNF-alpha in DCA group were reduced to 68%,
      75% and 63% of DC values, respectively. CONCLUSIONS: The antioxidant and anti
      inflammatory properties of CA may protect tissues such as the liver from diabetes
      induced oxidative damage.

PMID- 28447513
TI  - Clinical utility of different anti-Mullerian hormone - AMH assays for the purpose
      of pregnancy prediction.
AB  - PURPOSE: Comparison of outcomes of IVF cycles where the AMH levels was measured
      with five different AMH kits: Immunotech (IOT), Beckman Coulter II Gen. RUO,
      Beckman Coulter II Gen. IVD (BC II IVD), Ansh Labs ultrasensitive (Ansh) and the
      automated Elecsys Roche assay. METHODS: Retrospective analysis of clinical data
      for 3693 cycles. RESULTS: In women < 35 years with low (<0.6 ng/ml) and high
      (>1.4 ng/ml) AMH concentrations, and in those > 39 years with medium (>=0.6 and
      <=1.4 ng/ml) and high AMH concentrations the clinical pregnancy rate differed
      significantly among groups of patients whose AMH level was measured with
      different kits. In those subgroups, the highest rates were recorded for the BC II
      IVD and Ansh groups, while the lowest in the IOT group. AMH concentrations
      differed significantly between different kits in all age groups (the highest in
      each age group was for the IOT kit and the lowest for BC II IVD). AMH correlates
      positively with antral follicle count, MII and number of oocytes retrieved.
      CONCLUSIONS: This study demonstrated that we could expect very different
      pregnancy rates with the same AMH results depending on the AMH kit used. That
      would means, different values of AMH could similarly lead to misleading clinical
      decisions in IVF.

PMID- 28447515
TI  - Combination of subxiphoid and intercostal uniportal video-assisted thoracoscopic
      surgery for bilateral lung lesions: report of two cases and review of the
      literature.
AB  - Uniportal video-assisted thoracic surgery (VATS) is carried out to reduce
      postoperative pain after treatment of thoracic diseases. Here, we report a novel
      method that combines a subxiphoid and intercostal uniportal VATS approach that
      can be used to treat bilateral pulmonary lesions simultaneously. The first case
      is a 50-year-old female with bilateral pulmonary lesions who received left lower
      lobectomy associated with right middle lobe wedge resection synchronously; the
      other case is a 14-year-old male who was admitted for resection of bilateral lung
      metastases as a result of previous osteosarcoma. We combined a subxiphoid
      approach with intercostal uniportal surgical procedure for bilateral pulmonary
      lesions. Less postoperative pain, faster postoperative recovery, and a better
      aesthetic effect are possible superiorities of this method if patients are
      selected carefully. Our results show that the combining of a subxiphoid approach
      with intercostal uniportal VATS is a feasible and efficient surgical procedure
      for bilateral pulmonary lesions, with good outcomes. Moreover, this procedure is
      more suitable for patients with bilateral pulmonary lesions.

PMID- 28447516
TI  - Expression of glycoprotein VI in vascular endothelial cells.
AB  - Glycoprotein (GP) VI, a collagen receptor, plays an important role in collagen
      mediated platelet aggregation and adhesion. To date, GPVI expression has been
      found only in platelets and megakaryocytes. In the present studies, we have
      demonstrated that GPVI was also expressed in cultured human umbilical vein
      endothelial cells (HUVEC) at both transcript and protein levels. Using a GPVI
      specific probe, a ~6-kb band was detected in HUVEC as well as in platelets and
      megakaryoblastic cell lines by Northern blotting. Using polyclonal antibodies
      raised against platelet GPVI peptides, the same size band (57 kDa) was labeled
      with convulxin (CVX) after immuno-precipitation in both HUVEC and platelet
      lysates. In addition, a ~70-kDa band was also labeled in HUVEC. Surface
      expression of GPVI in HUVEC was confirmed by flow cytometry with GPVI-specific
      IgG or by direct labeling with FITC-conjugated CVX. Since HUVEC lack FcRgamma
      chain that forms complex with GPVI in platelets for signaling process, the
      function of GPVI in vascular endothelial cells remains to be determined.

PMID- 28447514
TI  - Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination
      through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and
      restriction of mature oligodendrocytes apoptosis.
AB  - CONTEXT: Ellagic acid (EA) is a natural phenol antioxidant with various
      therapeutic activities. However, the efficacy of EA has not been examined in
      neuropathologic conditions. OBJECTIVE: In vivo neuroprotective effects of EA on
      cuprizone (cup)-induced demyelination were evaluated. MATERIAL AND METHODS:
      C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce
      oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC). EA
      was administered at different doses (40 or 80 mg/kg body weight/day/i.p.) from
      the first day of cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin
      oligodendrocyte glycoprotein (MOG+)/caspase-3+ cells), gliosis (H&E staining,
      glial fibrillary acidic protein (GFAP+) and macrophage-3 (Mac-3+) cells) and
      inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal
      cell-derived factor 1 alpha (SDF-1alpha) or CXCL12] during cup intoxication were
      examined. RESULTS: High dose of EA (EA-80) increased mature oligodendrocytes
      population (MOG+ cells, p < 0.001), and decreased apoptosis (p < 0.05) compared
      with the cup mice. Treatment with both EA doses did not show any considerable
      effects on the expression of CXCL12, but significantly down-regulated the
      expression of IL-17 and up-regulated the expression of IL-11 in mRNA levels
      compared with the cup mice. Only treatment with EA-80 significantly decreased the
      population of active macrophage (MAC-3+ cells, p < 0.001) but not reactive
      astrocytes (GFAP+ cells) compared with the cup mice. DISCUSSION AND CONCLUSION:
      In this model, EA-80 effectively reduces lesions via reduction of
      neuroinflammation and toxic effects of cup on mature OLGs. EA is a suitable
      therapeutic agent for moderate brain damage in neurodegenerative diseases such as
      multiple sclerosis.

PMID- 28447519
TI  - Errata.

PMID- 28447526
TI  - Everyday technology use among older adults in Sweden and Japan: A comparative
      study.
AB  - BACKGROUND: As context may impact everyday technology (ET) use it is relevant to
      study this within different contexts. AIMS: To examine the usefulness of the
      Everyday Technology Use Questionnaire (ETUQ) in different contexts by
      investigating and comparing (1) the level of challenge of ETs in the ETUQ and (2)
      the relevance of and perceived ability to use ET in samples of Swedish and
      Japanese older adults. MATERIALS AND METHODS: The Swedish and the Japanese
      samples (n = 86/86) were interviewed using the ETUQ about relevance of and
      perceived ability to use ET. Data were analyzed using Rasch analysis, chi square
      and a general linear model. Moreover, Differential Item Functioning (DIF) was
      investigated. RESULTS: The hierarchy of ETs' level of challenge was generally
      stable in the two contexts. On group-level, the relevance was somewhat higher and
      the perceived ability to use ET significantly higher in the Swedish sample than
      in the Japanese. CONCLUSIONS AND SIGNIFICANCE: The similarities and differences
      between the technological landscapes of Sweden and Japan could be detected by
      ETUQ, demonstrating its usefulness in both countries. The potential causes to the
      differences in relevance of and perceived ability to use ET between older adults
      in Sweden and Japan need further exploration.

PMID- 28447517
TI  - Hepatoprotective potential of Phyllanthus muellarianus leaf extract: studies on
      hepatic, oxidative stress and inflammatory biomarkers.
AB  - CONTEXT: Leaves of Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) are
      widely used in the management of liver disorders in Nigeria. However, no there is
      no scientific validation to support this use. OBJECTIVE: Hepatoprotective effect
      of Phyllanthus muellarianus aqueous leaf extract was investigated in
      acetaminophen-induced liver injury mice. MATERIALS AND METHODS: Hepatoprotective
      effect of Phyllanthus muellarianus aqueous leaf extract was evaluated in
      acetaminophen-induced hepatic damage in Swiss albino mice using biomarkers of
      hepatocellular indices, oxidative stress, proinflammatory factors and lipid
      peroxidation. Mice received distilled water, 100, 200, or 400 mg/kg b.w of
      Phyllanthus muellarianus aqueous leaf extract, respectively, for seven days.
      Treatment groups were challenged with 300 mg/kg b.w of acetaminophen on the sixth
      day. RESULTS: Oral administration of Phyllanthus muellarianus aqueous leaf
      extract significantly (p < 0.05) attenuates acetaminophen-mediated alterations in
      serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase,
      albumin and total bilirubin by 76.56, 85.41, 89.39, 82.77 and 78.38%. Similarly,
      acetaminophen-mediated decrease in activities of superoxide dismutase, catalase,
      glutathione peroxidase, glutathione reductase and glucose 6-phosphate
      dehydrogenase were significantly attenuated in the liver of mice by 85.10, 80.81,
      80.45, 76.23 and 95.22%, respectively. Increased levels of conjugated dienes,
      lipid hydroperoxides, malondialdehyde, protein carbonyl, fragmented DNA, tumor
      necrosis factor-alpha, interleukin-6 and -8 were significantly lowered by
      Phyllanthus muellarianus aqueous leaf extract. CONCLUSION: Overall, results of
      this study show that Phyllanthus muellarianus halted acetaminophen-mediated
      hepatotoxicity due to its capability to enhance antioxidant enzymes.

PMID- 28447528
TI  - Inhibition of NF-kB Renders Cells more Vulnerable to Apoptosis Induced by Amyloid
      beta Peptides.
AB  - One of the mechanisms leading to neurodegeneration during Alzheimer's disease
      (AD) is amyloid beta peptide neurotoxicity. In response to a variety of stress
      insults, namely oxidative stress, the transcription factor NF-kB can be
      activated. We have previously shown that amyloid beta peptides 25-35 and 1-40
      (Abeta 25-35 and Abeta 1-40) induces cell death. In response to Abeta 25-35 or 1
      40 treatment, we observed an increase in superoxide dismutase (SOD) activity in
      NT2 cells. Amyloid beta peptides also induced an increase in SOD expression
      levels. This could result from NF-kB activation, as determined by the expression
      of p65. We observed that the NF-kB inhibitor, PDTC, prevented SOD overexpression
      after Abeta treatment. Previously we have shown that Abeta peptides could
      activate caspases-mediated apoptotic cell death. In this study, we analyzed if NF
      kB activation prevented cells from caspases-activation and we also observed that
      inhibition of NF-kB by PDTC induced an increase in caspase-3 and caspase-6
      activation. Taken together, these data suggest that pharmacological induction of
      NF-kB can be a potential target in Alzheimer's disease treatment.

PMID- 28447527
TI  - Serum thyroid hormone levels among Chinese pregnant women.
AB  - AIM: The aim of this study is to examine gestational serum thyroid hormone levels
      and influencing factors among Chinese pregnant women with high dietary iodine
      intake. METHODS: The study was conducted from 2011 and 2013 in Zhoushan Women &
      Children's Hospital, Zhejiang, China. A total of 1991 pregnant women were
      enrolled and their serum levels of free thyroid hormones (FT4, FT3, and TSH) were
      detected by chemiluminescence method. RESULTS: Gestational serum FT4 and FT3
      decreased with gestational week while TSH increased. Furthermore, the prevalence
      rate of subclinical hypothyroid increased with gestational stages, especially in
      the third trimester. Women aged more than 30 years had lower FT4 and FT3 in the
      first trimester and lower FT4 in the second trimester. No significant difference
      was found in the association of gestational serum thyroid hormones with maternal
      height and the gender of fetuses. CONCLUSION: Gestational serum thyroid hormones
      significantly changed with gestational week and were associated with the age of
      women. Specific normal range of thyroid hormones might be modified so as to
      better evaluate the thyroid hormone levels of pregnant women during pregnancy.

PMID- 28447529
TI  - ESR Spin Trapping Studies of Free Radicals Generated from Nitrofuran Derivative
      Analogues of Nifurtimox by Electrochemical and Trypanosoma cruzi Reduction.
AB  - Electron spin resonance (ESR) spectra of radicals obtained from two analogues of
      the antiprotozoal drug nifurtimox by electrolytic and Trypanosoma cruzi reduction
      were analyzed. The electrochemistry of these compounds was studied using cyclic
      voltammetry. STO 3-21G ab initio and INDO molecular orbital calculations were
      performed to obtain the optimized geometries and spin distribution, respectively.
      The antioxidant effect of glutathione on the nitroheterocycle radical was
      evaluated. DMPO spin trapping was used to investigate the possible formation of
      free radicals in the trypanosome microsomal system. Nitro1 and Nitro2 nitrofuran
      analogues showed better antiparasitic activity than nifurtimox. Nitro2 produced
      oxygen redox cycling in T. cruzi epimastigotes. The ESR signal intensities were
      consistent with the trapping of either the hydroxyl radical or the Nitro2
      analogue radicals. These results are in agreement with the biological observation
      that Nitro2 showed anti-Chagas activity by an oxidative stress mechanism.

PMID- 28447530
TI  - a-Tocopherol Content and a-Tocopherol Transfer Protein Expression in Leukocytes
      of Children with Acute Leukemia.
AB  - alpha-Tocopherol (a form of vitamin E) is a fat-soluble vitamin that can prevent
      lipid peroxidation of cell membranes. This antioxidant activity of alpha
      tocopherol can help to prevent cardiovascular disease, atherosclerosis and
      cancer. We investigated the alpha-tocopherol level and the expression of alpha
      tocopherol transfer protein (alpha-TTP) in the leukocytes of children with
      leukemia. The plasma and erythrocyte alpha-tocopherol levels did not differ
      between children with leukemia and the control group. However, lymphocytes from
      children with leukemia had significantly lower alpha-tocopherol levels than
      lymphocytes from the controls (58.4+/-39.0 ng/mg protein versus 188.9+/-133.6,
      respectively; p<0.05), despite the higher plasma alpha-tocopherol/cholesterol
      ratio in the leukemia group (5.83+/-1.64 MUmol/mmol versus 4.34+/-0.96,
      respectively; p<0.05). No significant differences in the plasma and leukocyte
      levels of isoprostanes (the oxidative metabolites of arachidonic acid) were seen
      between the leukemia patients and controls. The plasma level of acrolein, a
      marker of oxidative stress, was also similar in the two groups. Investigation of
      alpha-TTP expression by leukocytes using real-time PCR showed no difference
      between the two groups. These findings suggest that there may be comparable
      levels of lipid peroxidation in children with untreated leukemia and controls,
      despite the reduced alpha-tocopherol level in leukemic leukocytes.

PMID- 28447531
TI  - Treatment of foot varicose veins: A study of 119 consecutive patients.
AB  - Objective To analyze the outcomes of 119 (188 feet) patients undergoing foot
      varicose vein phlebectomy with and without sclerotherapy between 2013 and 2015.
      Methods Legs and feet were treated in one single procedure. Clinical and
      ultrasound assessments were carried out at 7, 30, and 90 days for visualization
      of the sapheno-femoral and sapheno-popliteal junctions and the deep vein system.
      Results Mean age was 50 +/- 12 years (25-79 years); 67 patients were female
      (56.3%). Median venous clinical severity score was 4 (range 2-5) before and 1
      (range 0-2) at 90 days ( p < 0.001). Edema and transient paresthesia were the
      most frequent complications (13 (10.92%) and 11 (9.24%) patients, respectively).
      All complications were resolved at 90 days except one case of edema (resolved
      after 150 days with compression stockings and lymphatic drainage manual therapy).
      Conclusions Symptomatic foot varicose vein intervention was safe and effective.
      Further studies should focus on assessment of vein-specific quality of life
      questionnaires.

PMID- 28447535
TI  - Natural occurrence of fumonisins and characteristics of pamonhas sweet type from
      Southern Brazil.
AB  - Fresh and frozen pamonhas, a native Brazilian food made with sweet corn (Zea mays
      L.), similar to the Mexican tamal, which has been incorporated into the country's
      diet, were investigated for fumonisins (FBs: FB1 and FB2) contamination and
      product characteristics. The laboratory conditions of the applied fumonisins
      method with liquid chromatography and fluorescence detection were validated. Five
      out of the total samples showed FBs contamination above the national maximum
      level of 1000-1500 ug/kg. Despite this, in 59.6% (31) of the samples FB1 and in
      23.1% (12) FB2 could be detected. The pamonhas characteristics did not show
      uniformity among the brands surveyed. The moisture content of 59.4% and water
      activity of 0.97 for both (fresh and frozen) samples showed to be suitable
      conditions for fungal growth. One sample had a quite high pH. It is essential to
      establish guidance criteria for pamonha production by the regulatory agencies.

PMID- 28447536
TI  - Health-Related Quality of Life of Nepalese Children With Leukemia Using Pediatric
      Quality of Life Inventory 4.0 Generic Core Scale.
AB  - Health-related quality of life (HRQOL) is an essential measure to consider when
      evaluating the full impact of illness in children diagnosed with leukemia. The
      purpose of the current study was to assess the overall HRQOL and specific
      functioning subscales of Nepalese children with leukemia using Pediatric Quality
      of Life Inventory 4.0 Generic Core Scale (PedsQL 4.0), compare self-report with
      parent proxy report of HRQOL and to identify the determinants affecting HRQOL.
      After cultural linguistic validation of PedsQL, a descriptive cross-sectional
      study was conducted on 43 children with leukemia and their parents in B. P.
      Koirala Memorial Cancer Hospital, Bharatpur via interview schedule. Among the
      subscales of HRQOL both the child's self-report and parent proxy report scores
      were highest in social functioning and lowest in emotional functioning subscale.
      Intraclass correlation coefficient between proxy reports and self-reports were
      highest (0.828) in physical functioning and lowest (0.493) in social functioning
      subscales. Age group was significantly associated with the total score, physical
      functioning subscale, and emotional functioning subscale of only proxy scores.
      Leukemic children's age-specific needs should be addressed properly to improve
      their overall HRQOL.

PMID- 28447537
TI  - Diabetes, a global public health challenge with a high epidemiological and
      economic burden on health systems in Latin America.
AB  - This manuscript presents the results of an analysis that highlights the
      challenges of diabetes as a global public health problem. The analysis was
      conducted in two phases: the first phase deals with primary data and results of a
      longitudinal study to provide evidence on the Mexican case. Regarding
      epidemiological changes between 2014 and 2016, there is an increase of 9-13% (p <
      .001). Comparing the economic burden from epidemiological changes in 2014 versus
      2016 (p < .05), there is a 26% increase. The total amount spent on diabetes in
      2015 (US dollars) was $ 8,974,662,570. This includes $ 3,981,426,810 in direct
      costs and $ 4993,235,752 in indirect costs. The second phase emphasises the
      analysis of diabetes as a major global public health challenge in the Americas.
      For this purpose a comparative analysis of epidemiological trends was carried out
      in seven selected Latin American countries (LACs). The results of both phases
      showed evidence leading to the conclusion that if the risk factors and models of
      health care remain as they currently are in LACs, there will be a high economic
      impact to patients' pockets and to health systems, which could lead to financial
      collapse.

PMID- 28447538
TI  - Imitation Learning Errors Are Affected by Visual Cues in Both Performance and
      Observation Phases.
AB  - Mechanisms of action imitation were examined. Previous studies have suggested
      that success or failure of imitation is determined at the point of observing an
      action. In other words, cognitive processing after observation is not related to
      the success of imitation; 20 university students participated in each of three
      experiments in which they observed a series of object manipulations consisting of
      four elements (hands, tools, object, and end points) and then imitated the
      manipulations. In Experiment 1, a specific intially observed element was color
      coded, and the specific manipulated object at the imitation stage was identically
      color coded; participants accurately imitated the color coded element. In
      Experiment 2, a specific element was color coded at the observation but not at
      the imitation stage, and there were no effects of color coding on imitation. In
      Experiment 3, participants were verbally instructed to attend to a specific
      element at the imitation stage, but the verbal instructions had no effect. Thus,
      the success of imitation may not be determined at the stage of observing an
      action and color coding can provide a clue for imitation at the imitation stage.

PMID- 28447539
TI  - Feasibility of preference-driven radiotherapy dose treatment planning to support
      shared decision making in anal cancer.
AB  - PURPOSE/OBJECTIVE: Chemo-radiotherapy is an established primary curative
      treatment for anal cancer, but clinically equal rationale for different target
      doses exists. If joint preferences (physician and patient) are used to determine
      acceptable tradeoffs in radiotherapy treatment planning, multiple dose plans must
      be simultaneously explored. We quantified the degree to which different toxicity
      priorities might be incorporated into treatment plan selection, to elucidate the
      feasible decision space for shared decision making in anal cancer radiotherapy.
      MATERIAL AND METHODS: Retrospective plans were generated for 22 anal cancer
      patients. Multi-criteria optimization handles dynamically changing priorities
      between clinical objectives while meeting fixed clinical constraints. Four unique
      dose distributions were designed to represent a wide span of clinically relevant
      objectives: high-dose preference (60.2 Gy tumor boost and 50.4 Gy to elective
      nodes with physician-defined order of priorities), low-dose preference (53.75 Gy
      tumor boost, 45 Gy to elective nodes, physician-defined priorities), bowel
      sparing preference (lower dose levels and priority for bowel avoidance) and
      bladder sparing preference (lower dose levels and priority for bladder
      avoidance). RESULTS: Plans satisfied constraints for target coverage. A senior
      oncologist approved a random subset of plans for quality assurance. Compared to a
      high-dose preference, bowel sparing was clinically meaningful at the lower
      prescribed dose [median change in V45Gy: 234 cm3; inter-quartile range (66; 247);
      p < .01] and for a bowel sparing preference [median change in V45Gy: 281 cm3;
      (73; 488); p < .01]. Compared to a high-dose preference, bladder sparing was
      clinically meaningful at the lower prescribed dose [median change in V35Gy: 13.7%
      points; (0.3; 30.6); p < .01] and for a bladder sparing preference [median change
      in V35Gy: 30.3%-points; (12.4; 43.1); p < .01]. CONCLUSIONS: There is decision
      space available in anal cancer radiotherapy to incorporate preferences, although
      tradeoffs are highly patient-dependent. This study demonstrates that preference
      informed dose planning is feasible for clinical studies utilizing shared decision
      making.

PMID- 28447541
TI  - Sensor array for the detection of organic and inorganic contaminants in post
      consumer recycled plastics for food contact.
AB  - Post-consumer recycled (PCR) plastic material is made by collecting used plastic
      products (e.g., bottles and other plastic packaging materials) and reprocessing
      them into solid-state pellets or flakes. Plastic recycling has positive
      environmental benefits, but may also carry potential drawbacks due to unwanted
      organic and inorganic contaminants. These contaminants can migrate into food
      packaging made from these recycled plastic materials. The purpose of this
      research was to identify economically viable real-time monitoring technologies
      that can be used during the conversion of virgin and recycled resin feedstocks
      (i.e., various blends of virgin pellets and recycled solid-state pellet or
      mechanically ground flake) to final articles to ensure the safety, quality and
      sustainability of packaging feedstocks. Baseline analysis (validation) of real
      time technologies was conducted using industry-standard practices for polymer
      analysis. The data yielded supervised predictive models developed by training
      sessions completed in a controlled laboratory setting. This technology can be
      employed to evaluate compliance and aid converters in commodity sourcing of resin
      without exceeding regulatory thresholds. Furthermore, this technology allowed for
      real-time decision and diversion strategies during the conversion of resin and
      flake to final articles or products to minimise the negative impact on human
      health and environmental exposure.

PMID- 28447542
TI  - Assessing outcomes of educational videos in group visits for patients with
      chronic pain at an academic primary care clinic.
AB  - OBJECTIVES: This study evaluates the impact of pain education group visits on
      patients with chronic non-cancer pain (CNCP). The primary outcome of the study
      was to evaluate patients' functional status and secondary outcomes included
      knowledge, behavior, and satisfaction, before and after participation in the pain
      education group visits. METHODS: Locally produced patient educational videos on
      chronic non-cancer pain were delivered during patient group visits led by a
      healthcare provider. Study participants included patients with CNCP pain in an
      academic general medicine practice. The primary outcome was functional status,
      measured by the Pain Intensity, Enjoyment of life, and General Activity (PEG)
      score and the Oswestry Disability Index. Secondary outcomes were evaluated
      through a pre- and post-intervention knowledge assessment and chart review of
      opioid use and utilization of emergency and urgent care services. A satisfaction
      survey was administered after each group visit. RESULTS: Thirty-five patient
      group visits were analyzed and 14 patient charts reviewed. A moderately positive
      correlation was observed between PEG and Oswestry Disability Index (r = 0.47, p <
      0.05). Patient knowledge improved after watching the videos and participating in
      group discussion. The median amount of daily morphine equivalents for patients (n
      = 14) was 17.5mg (range 0-120mg) at the first study, and decreased to 12.5mg
      (range 0-110mg) at the last study visit (p = 0.39). None of the 14 patients
      utilized emergency or urgent care services for pain during the study. Overall,
      patient satisfaction scores with the intervention were high. CONCLUSION: Group
      visits providing patient education about CNCP may benefit patients' knowledge
      about this clinical condition, and was received with high patient satisfaction.
      Further investigation is needed to evaluate longer-term knowledge retention,
      sustainability of improvements resulting from the intervention, and longer-term
      effects of the intervention on functional status.

PMID- 28447543
TI  - Human EGF-derived direct and reverse short linear motifs: conformational dynamics
      insight into the receptor-binding residues.
AB  - Short linear motifs (SLiMs) have been recognized to perform diverse functions in
      a variety of regulatory proteins through the involvement in protein-protein
      interactions, signal transduction, cell cycle regulation, protein secretion, etc.
      However, detailed molecular mechanisms underlying their functions including roles
      of definite amino acid residues remain obscure. In our previous studies, we
      demonstrated that conformational dynamics of amino acid residues in oligopeptides
      derived from regulatory proteins such as alpha-fetoprotein (AFP), carcino
      embryonic antigen (CEA), and pregnancy specific beta1-glycoproteins (PSGs)
      contributes greatly to their biological activities. In the present work, we
      revealed the 22-member linear modules composed of direct and reverse AFP14-20
      like heptapeptide motifs linked by CxxGY/FxGx consensus motif within epidermal
      growth factor (EGF), growth factors of EGF family and numerous regulatory
      proteins containing EGF-like modules. We showed, first, the existence of
      similarity in amino acid signatures of both direct and reverse motifs in terms of
      their physicochemical properties. Second, molecular dynamics (MD) simulation
      study demonstrated that key receptor-binding residues in human EGF in the aligned
      positions of the direct and reverse motifs may have similar distribution of
      conformational probability densities and dynamic behavior despite their distinct
      physicochemical properties. Third, we found that the length of a polypeptide
      chain (from 7 to 53 residues) has no effect, while disulfide bridging and
      backbone direction significantly influence the conformational distribution and
      dynamics of the residues. Our data may contribute to the atomic level structure
      function analysis and protein structure decoding; additionally, they may provide
      a basis for novel protein/peptide engineering and peptide-mimetic drug design.

PMID- 28447544
TI  - Can perceivers recognise emotions from spontaneous expressions?
AB  - Posed stimuli dominate the study of nonverbal communication of emotion, but
      concerns have been raised that the use of posed stimuli may inflate recognition
      accuracy relative to spontaneous expressions. Here, we compare recognition of
      emotions from spontaneous expressions with that of matched posed stimuli.
      Participants made forced-choice judgments about the expressed emotion and whether
      the expression was spontaneous, and rated expressions on intensity (Experiments 1
      and 2) and prototypicality (Experiment 2). Listeners were able to accurately
      infer emotions from both posed and spontaneous expressions, from auditory,
      visual, and audiovisual cues. Furthermore, perceived intensity and
      prototypicality were found to play a role in the accurate recognition of emotion,
      particularly from spontaneous expressions. Our findings demonstrate that
      perceivers can reliably recognise emotions from spontaneous expressions, and that
      depending on the comparison set, recognition levels can even be equivalent to
      that of posed stimulus sets.

PMID- 28447545
TI  - Effects of a Family-based Diabetes Intervention on Behavioral and Biological
      Outcomes for Mexican American Adults.
AB  - Purpose The purpose of the study was to investigate the effects of a family-based
      self-management support intervention for adults with type 2 diabetes (T2DM).
      Methods Using a 2-group, experimental repeated measures design, 157 dyads
      (participant with T2DM and family member) were randomly assigned to an
      intervention (education, social support, home visits, and telephone calls) or a
      wait list control group. Data were collected at baseline, postintervention (3
      months), and 6 months postintervention. A series of 2 * 3 repeated measures
      ANOVAs were used to test the hypotheses with interaction contrasts to assess
      immediate and sustained intervention effects. Results Significant changes over
      time were reported in diet self-management, exercise self-management, total self
      management, diabetes self-efficacy for general health and total diabetes self
      efficacy, physician distress, regimen distress, interpersonal distress, and total
      distress. There were likewise sustained effects for diet self-management, total
      self-management, diabetes self-efficacy for general health, total self-efficacy,
      physician distress, regimen distress, and interpersonal distress. Conclusions
      Results support and extend prior research documenting the value of culturally
      relevant family-based interventions to improve diabetes self-management and
      substantiate the need for intensive, longer, tailored interventions to achieve
      glycemic control.

PMID- 28447546
TI  - Application of an indicator-immobilized-gel-sheet for measuring the pH
      surrounding a calcium phosphate-based biomaterial.
AB  - The present study was designed to investigate the local microenvironment of
      octacalcium phosphate in a granule form upon biomolecules adsorption utilizing an
      indicator-immobilized-gel-sheet for measuring pH. We previously showed that
      octacalcium phosphate enhances bone regeneration during its progressive
      hydrolysis into hydroxyapatite if implanted in bone defects. The gel-sheet was
      made from a photocrosslinkable prepolymer solution, which can easily immobilize a
      pH indicator (bromothymol blue; BTB) in the hydrogel. The indicator-immobilized
      gel-sheet was mounted on a biochip which was made of polydimethylsiloxane (PDMS)
      with a flow channel. The pH value was calculated by detecting the color changes
      in the gel-sheet and displayed as the pH distribution. After pre-adsorption of
      bovine albumin, beta-lactoglobuline or cytochrome C onto octacalcium phosphate
      granules, the granules with the gel-sheet were further incubated in Tris-HCl
      buffer solution in the absence or presence of fluoride, known as an accelerator
      of octacalcium phosphate hydrolysis. pH values of the gel-sheet surrounding
      octacalcium phosphate granules showed a decrease from pH 7.4 to 6.6 in relation
      to the proteins adsorbed. Overall, the proposed pH-sensitive gel can be used to
      detect the pH around octacalcium phosphate granules with a high spatial
      resolution.

PMID- 28447547
TI  - Urinary bladder extracellular matrix hydrogels and matrix-bound vesicles
      differentially regulate central nervous system neuron viability and axon growth
      and branching.
AB  - Central nervous system neurons often degenerate after trauma due to the
      inflammatory innate immune response to injury, which can lead to neuronal cell
      death, scarring, and permanently lost neurologic function. Extracellular matrix
      bioscaffolds, derived by decellularizing healthy tissues, have been widely used
      in both preclinical and clinical studies to promote positive tissue remodeling,
      including neurogenesis, in numerous tissues, with extracellular matrix from
      homologous tissues often inducing more positive responses. Extracellular matrix
      hydrogels are liquid at room temperature and enable minimally invasive
      extracellular matrix injections into central nervous system tissues, before
      gelation at 37C. However, few studies have analyzed how extracellular matrix
      hydrogels influence primary central nervous system neuron survival and growth,
      and whether central nervous system and non-central nervous system extracellular
      matrix specificity is critical to neuronal responses. Urinary bladder
      extracellular matrix hydrogels increase both primary hippocampal neuron survival
      and neurite growth to similar or even greater extents, suggesting extracellular
      matrix from non-homologous tissue sources, such as urinary bladder matrix
      extracellular matrix, may be a more economical and safer alternative to
      developing central nervous system extracellular matrices for central nervous
      system applications. Additionally, we show matrix-bound vesicles derived from
      urinary bladder extracellular matrix are endocytosed by hippocampal neurons and
      positively regulate primary hippocampal neuron neurite growth. Matrix-bound
      vesicles carry protein and RNA cargos, including noncoding RNAs and miRNAs that
      map to the human genome and are known to regulate cellular processes. Thus,
      urinary bladder matrix-bound vesicles provide natural and transfectable cargoes
      which offer new experimental tools and therapeutic applications to study and
      treat central nervous system neuron injury.

PMID- 28447548
TI  - Preparation of wormlike polymeric nanoparticles coated with silica for delivery
      of methotrexate and evaluation of anticancer activity against MCF7 cells.
AB  - Methotrexate is one of the most effective drugs that is commonly used in the
      treatment of cancer. However, its application is limited due to low solubility,
      high toxicity and rapid metabolism. Therefore, in the present study, worm-like
      polymeric nanoparticles as carrier of methotrexate were prepared using
      biodegradable copolymers (mPEG-PCL). The impact of nanoparticles' geometry on the
      loading, delivery and drug's anti-cancer activity was investigated. The di-block
      copolymer mPEG-PCL was being synthesized by a ring opening polymerization of E
      caprolactone in the presence of mPEG as the initiator and Sn(oct)2 as the
      catalyst. It was used for the preparation of worm-like micelles and coated with
      silica, so that their structures are stable after drying. The synthesized
      copolymers and nanoparticles were characterized by FTIR, HNMR, GPC, XRD, TGA,
      DLS, and FE-SEM analyses. The efficiencies of drug loading and release of
      nanoparticles as in vitro, was studied by high performance liquid chromatography.
      The MTT method was used to estimate the toxicity on MCF-7 cell category. The
      obtained results showed that the nanoparticles were worm-like particles with less
      than 150 nm diameter and about 1 um length. The loading and encapsulation
      efficiencies of drug by the worm-like nanoparticles were 3.5 +/- 0.14% and 65.6
      +/- 0.12%, respectively, while they were obtained as 2.1 +/- 0.08% and 26 +/-
      0.10%, respectively, for spherical nanoparticles. The methotrexate diffusional
      behavior of worm-like nanoparticles was compared with that of the spherical ones.
      On the other hand, the anti-cancer activity of MTX-loaded nanoparticles was more
      than the free drug. The results of the MTT assay showed strong and dose-dependent
      inhibition of cell (MCF-7 category) growth by the nanoparticles compared with
      MTX. The inhibitory concentrations (IC50 i.e. reduction viability of cell to 50%)
      obtained for worm-like, spherical nanoparticles and free drug (incubation times
      72 h) were 8.25 +/- 0.20, 9.15 +/- 0.17, 12.28 +/- 0.15 ug/mL, respectively. It
      can be concluded that application of non-spherical nanoparticles is a better and
      more effective strategy for controlled and slow release of methotrexate in the
      treatment of cancer.

PMID- 28447550
TI  - Food safety and tackling obesity.

PMID- 28447549
TI  - A child with severe iron-deficiency anemia and a complex TMPRSS6 genotype.
AB  - OBJECTIVES: We report a case of a 7-year-old girl with severe hypochromic
      microcytic anemia, who was unresponsive to classical iron supplements. We
      suspected IRIDA, iron-refractory iron-deficiency anemia, a genetic iron
      metabolism disorder, caused by TMPRSS6 variations. TMPRSS6 encodes matriptase-2,
      a negative regulator of hepcidin, and its pathological variants are related to
      normal to high levels of hepcidin. We analyzed the TMPRSS6 gene and we improved
      clinical management of the patient, selecting the appropriate supplementation
      therapy. Intervention & Technique: The parenteral iron therapy was started, but
      the patient was only partially responsive and the anemia persisted. To confirm
      the diagnosis, the TMPRSS6 gene sequence was analyzed by DNA sequencing and other
      relevant biochemical parameters were evaluated. RESULTS: The TMPRSS6 sequence
      analysis showed a complex genotype with a rare heterozygous missense variant, in
      addition to other common polymorphisms. The serum hepcidin value was normal. We
      unexpectedly observed a normalization of patient's hemoglobin (Hb) levels only
      after liposomal iron treatment. DISCUSSION AND CONCLUSION: The proband was
      symptomatic for IRIDA during a critical phase of growth and development, but we
      did not find a clearly causative genotype. A long-term result, improving stably
      patient's Hb levels, was obtained only after liposomal iron supplementation.
      Children may be at greater risk for iron deficiency and the degree of anemia as
      well as the response to the iron supplements varies markedly patient to patient.
      Here, we show the importance of comprehensive study of these patients in order to
      collect useful information about genotype-phenotype association of genes involved
      in iron metabolism.

PMID- 28447552
TI  - One is the loneliest number: insight into a silent epidemic.

PMID- 28447553
TI  - Food safety training: meeting the challenges.

PMID- 28447556
TI  - Fraud resilience and food and drink businesses.

PMID- 28447558
TI  - The value of a multidisciplinary approach to health.

PMID- 28447559
TI  - Training and supporting adults who influence nutrition of children under five.

PMID- 28447560
TI  - Whole Systems Obesity Programme.

PMID- 28447561
TI  - Efforts to reduce sugar intake: the case of Korea.

PMID- 28447562
TI  - Dosimetric advantages of a clinical daily adaptive plan selection strategy
      compared with a non-adaptive strategy in cervical cancer radiation therapy.
AB  - BACKGROUND: Radiation therapy (RT) using a daily plan selection adaptive strategy
      can be applied to account for interfraction organ motion while limiting organ at
      risk dose. The aim of this study was to quantify the dosimetric consequences of
      daily plan selection compared with non-adaptive RT in cervical cancer. MATERIAL
      AND METHODS: Ten consecutive patients who received pelvic irradiation, planning
      CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs
      were included. Non-adaptive plans were generated based on the PTV defined using
      the full bladder planning CT. For the adaptive strategy, multiple PTVs were
      created based on both planning CTs by ITVs of the primary CTVs (i.e., GTV,
      cervix, corpus-uterus and upper part of the vagina) and corresponding library
      plans were generated. Daily CBCTs were rigidly aligned to the full bladder
      planning CT for plan selection. For daily plan recalculation, selected CTs based
      on initial similarity were deformably registered to CBCTs. Differences in daily
      target coverage (D98% > 95%) and in V0.5Gy, V1.5Gy, V2Gy, D50% and D2% for
      rectum, bladder and bowel were assessed. RESULTS: Non-adaptive RT showed
      inadequate primary CTV coverage in 17% of the daily fractions. Plan selection
      compensated for anatomical changes and improved primary CTV coverage
      significantly (p < 0.01) to 98%. Compared with non-adaptive RT, plan selection
      decreased the fraction dose to rectum and bowel indicated by significant (p <
      0.01) improvements for daily V0.5Gy, V1.5Gy, V2Gy, D50% and D2%. However, daily
      plan selection significantly increased the bladder V1.5Gy, V2Gy, D50% and D2%.
      CONCLUSIONS: In cervical cancer RT, a non-adaptive strategy led to inadequate
      target coverage for individual patients. Daily plan selection corrected for day
      to-day anatomical variations and resulted in adequate target coverage in all
      fractions. The dose to bowel and rectum was decreased significantly when applying
      adaptive RT.

PMID- 28447563
TI  - Need for adjuvant chemotherapy after colon cancer surgery - has it decreased?

PMID- 28447564
TI  - Pretreatment late-phase DCE-MRI predicts outcome in locally advanced cervix
      cancer.
AB  - BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may
      provide prognostic biomarkers for cervix carcinoma. We have shown previously that
      the early phase of the signal intensity-versus-time curve (SITC) may have
      significant prognostic power. The purpose of the present investigation was to
      explore the prognostic value of the late phase of the SITC. MATERIAL AND METHODS:
      DCE-MRI data of 80 patients (FIGO stage IB-IVA) treated with concurrent
      chemoradiotherapy were examined. Four parameters were calculated from the late
      phase SITC: tumor volume with decreasing signal, tumor fraction with decreasing
      signal, tumor volume with increasing signal (TVIS), and tumor fraction with
      increasing signal. RESULTS: Multivariate analysis involving clinical parameters
      and late-phase SITC parameters suggested that TVIS is a strong independent
      prognostic factor for both disease-free and overall survival. When early-phase
      SITC parameters were included in the multivariate analysis, the early-phase SITC,
      but not the late-phase SITC, was found to have independent prognostic value.
      CONCLUSION: The late-phase SITC can provide prognostic factors for the outcome of
      cervix carcinoma, that is, a large tumor volume with increasing late-phase SITCs
      is associated with poor outcome. However, the prognostic power of the late-phase
      SITC is not as strong as that of the early-phase SITC.

PMID- 28447566
TI  - Pain, sensory disturbances and psychological distress are common sequelae after
      treatment of ductal carcinoma in situ: a cross-sectional study.
AB  - : Sequelae such as pain, sensory disturbances and psychological distress are well
      known after treatment for invasive breast cancer (IBC). Patients treated for
      ductal carcinoma in situ (DCIS) receive a similar treatment as low-risk IBC. The
      aim of this cross-sectional study was to describe prevalence of postoperative
      pain, sensory disturbances, psychological distress and rehabilitation needs among
      Danish women with DCIS. METHODS: A total of 574 women treated for DCIS in Denmark
      in 2013 and 2014 were enrolled and 473 (82%) completed a detailed questionnaire
      on demographic factors, pain, sensory disturbances, psychological aspects and
      rehabilitation needs 1-3 years after surgery. RESULTS: Median age was 60 years. A
      total of 33% of patients reported any pain and 12% reported moderate to severe
      pain in the area of surgery. Younger age (<50 years OR 4.7 (95% CI: 1.6-14.0, p =
      0.006)), aged 50 to 65 years OR 2.8 (95% CI: 1.1-7.0, p = 0.02) and anxiety and
      depression (measured by HADStotal >15 OR of 3.1 (95% CI: 1.5-6.3, p = 0.003))
      were significantly associated with moderate to severe pain. Approximately one
      third of the patients reported sensory disturbances such as pins and needles
      (32%), numbness (37%) and painful itch (30%) and 94 women (20%) reported anxiety
      >=8, 26 (6%) depression and 51 (11%) reported distress. CONCLUSIONS: This cross
      sectional study showed that women treated for DCIS suffered from pain, sensory
      disturbances and psychological impairment and had unmet rehabilitation needs.
      Further research is warranted, specifically addressing rehabilitation after
      diagnosis and treatment of DCIS.

PMID- 28447565
TI  - Risk factors for brain metastases in patients with metastatic colorectal cancer.
AB  - BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the
      incidence is suspected to rise as treatment of metastatic (m) CRC improves. The
      aim of this study was to identify possible biological and clinical
      characteristics at initial presentation of mCRC that could predict later risk of
      developing BM. Furthermore, we wished to estimate the incidence of BM in long
      term surviving patients. MATERIAL AND METHODS: We conducted a retrospective study
      on a Danish multicenter cohort of patients with mCRC who received cetuximab and
      irinotecan (CetIri) as third-line treatment. All patients had previously
      progression on 5-FU, irinotecan and oxaliplatin containing regimens and received
      CetIri treatment independent of RAS mutations status. We subsequently performed
      KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from
      primary tumor tissue. RESULTS: Totally, 480 patients were included in our study.
      BM were diagnosed in 42 [8.8%; 95% confidence interval (CI) 6.4-11.6%] patients.
      Patients with BM had a significantly longer survival from mCRC diagnosis than non
      BM patients (median = 32 versus 28 months, p = 0.001). On univariate cox
      regression analysis, the risk of developing BM was significantly increased in
      patients with rectal cancer (HR = 3.9; 95% CI = 1.2-13.3), metachronous
      metastatic disease (HR = 2.3; 95% CI = 1.2-4.4) and lung metastases (HR = 4.2;
      95% CI = 2.2-7.9). On multivariate cox regression analysis only lung metastases
      were significantly associated BM (HR = 3.5; 95% CI = 1.8-6.8). None of the
      investigated mutations were associated with BM. CONCLUSION: The incidence of BM
      was 8.8% in patients with mCRC who received third-line therapy. The most
      important risk factor for developing BM was lung metastases. Furthermore, rectal
      cancer, metachronous metastatic disease and long survival were linked to BM
      development.

PMID- 28447567
TI  - A longitudinal assessment of psychological distress after oesophageal cancer
      surgery.
AB  - BACKGROUND: Psychological distress is common among patients with oesophageal
      cancer. However, little is known about the course and predictors of psychological
      distress among patients treated with curative intent. Therefore, the aim of this
      study was to explore the prevalence, course and predictors of anxiety and
      depression in patients operated for oesophageal cancer, from prior to surgery to
      12 months post-operatively. METHODS: A prospective cohort of patients with
      oesophageal cancer (n = 218) were recruited from one high-volume specialist
      oesophago-gastric treatment centre (St Thomas' Hospital, London, UK). Anxiety and
      depression were assessed prior to surgery, 6 and 12 months post-operatively.
      Mixed-effects modelling was performed to investigate changes over time and to
      estimate the association between clinical and socio-demographic predictor
      variables and anxiety and depression symptoms. RESULTS: The proportion of
      patients with anxiety was 33% prior to surgery, 28% at 6 months, and 37% at 12
      months. Prior to surgery, 20% reported depression, 27% at 6 months, and 32% at 12
      month follow-up. Anxiety symptoms remained stable over time whereas depression
      symptoms appeared to increase from pre-surgery to 6 months, levelling off between
      6 and 12 months. Younger age, female sex, living alone and more severe self
      reported dysphagia (i.e., difficulty swallowing) predicted higher anxiety
      symptoms. In-hospital complications, greater limitations in activity status and
      more severe self-reported dysphagia were predictive of higher depression.
      CONCLUSIONS: Many patients report psychological distress during the first year
      following oesophageal cancer surgery. Whether improving the experience of
      swallowing difficulties may also reduce distress among these patients warrants
      further study.

PMID- 28447568
TI  - Age at menarche in relation to prenatal rainy season exposure and altitude of
      residence: results from a nationally representative survey in a tropical country 
      ERRATUM.

PMID- 28447576
TI  - The prognostic value of vascular endothelial growth factor in patients with renal
      cell carcinoma: a systematic review of the literature and meta-analysis.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) serum level or tumor
      expression may be prognostic in renal cell carcinoma (RCC). The purpose of this
      meta-analysis was to examine the prognostic value of serum VEGF level and tumor
      expression in patients with RCC. METHODS: PubMed and EMBASE databases were
      searched until September 26, 2016. Prospective and retrospective studies of RCC
      patients that had VEGF levels measured were included. Outcome measures were
      overall survival (OS), disease-specific survival (DSS), and progression-free
      survival (PFS). RESULTS: A total of 14 studies were included in the meta
      analysis. In patients with RCC, elevated serum VEGF level was not associated with
      OS (pooled hazard ratio [HR] = 1.16; 95% confidence interval [CI]: 0.52 to 2.60;
      p = 0.716), but was associated with poor DSS (pooled HR = 4.22; 95% CI: 2.02 to
      8.79; p < 0.001) and PFS (pooled HR = 1.50; 95% CI: 1.22 to 1.85; p < 0.001).
      Removal of one study, however, resulted in elevated serum level being associated
      with poorer OS. Tumor VEGF expression was not associated with OS (pooled HR =
      1.48; 95% CI: 0.74 to 2.95; p = 0.263), but was associated with worse DSS (pooled
      HR = 1.83; 95% CI: 1.24 to 2.71; p = 0.003). CONCLUSION: In patients with RCC,
      elevated serum VEGF level is associated with worse OS, DSS, and PFS, while tumor
      expression is only associated with worse DSS. The number of studies, however, was
      limited and the results should be interpreted with caution.

PMID- 28447577
TI  - Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock.
AB  - PURPOSE: ADAMTS13 level was evaluated as a predictor of mortality in patients
      with severe sepsis and septic shock, and compared with Acute Physiology and
      Chronic Health Evaluation II (APACHE II) scores. METHODS: This prospective
      observational study was conducted in the Medical and Surgical Intensive Care
      Units of King Khalid University Hospital. Detailed clinical evaluations were
      performed on 84 patients (56.08+/-18.18 years of age) with severe sepsis and
      septic shock. ADAMTS13 levels were determined (three blood samples at 24 hours
      intervals) and APACHE II scores, hematological profiles, indices of organ hypo
      perfusion, renal functions and coagulation profiles were recorded. Primary
      outcome was 30 days ICU mortality and secondary outcomes were its comparison with
      APACHE II score, length of ICU stay and use of vasopressor agents. RESULTS:
      Hypertension (53.6%) and diabetic mellitus (45.2%) were the commonest
      comorbidities. The median ADAMTS13 levels were 336.65, 339.35 and 313.9,
      respectively. ROC analysis showed maximum area under the curve for second
      ADAMTS13 (AUC=0.760) compared with first (AUC=0.660) and third samples
      (AUC=0.707) and APACHE II scores (AUC=0.662). Patients were divided into low and
      high ADAMTS13 groups according to the best cut-off point. Mortality was high in
      the low ADAMTS13 level group [OR=4.5]and was significantly associated with age,
      DBP, ADAMTS13, APACHE II score, DIC score and platelet count. ADAMTS13 (OR=5.3),
      APACHE II (OR=4.13) and DIC scores (OR=7.32) were significant risk factors for
      mortality. CONCLUSIONS: Low ADAMTS13 was associated with increased mortality in
      patients with severe sepsis and septic shock and was comparable to APACHE II
      scores for predicting mortality.

PMID- 28447578
TI  - Proprotein Convertase Subtilisin/Kexin type 9 affects insulin but not lipid
      metabolism in cystic fibrosis.
AB  - PURPOSE: Cystic Fibrosis (CF) is the most common genetic disorder and, with
      improved survival, glucose abnormalities have emerged as a major comorbidity.
      Proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulator of plasma LDL
      cholesterol homeostasis, is associated with lipid and glucose metabolism in
      healthy individuals. Here we report on the link between PCSK9 and markers of
      metabolism in CF. METHODS: Cross-sectional analysis was performed on CF patients
      (>= 18 years, N=94) from the Montreal Cohort, without known diabetes, and on
      healthy individuals (N=19). The levels of PCSK9 and lipid markers were quantified
      and all subjects underwent a 2 h oral glucose tolerance test. RESULTS: No
      significant differences in PCSK9 levels were found between healthy individuals
      and patients with CF, or between the groups with different degrees of glucose
      tolerance. No association was found between PCSK9 and markers of lipid
      metabolism; however, a positive correlation was found between PCSK9 and total
      insulin secretion and a negative one with insulin sensitivity in CF patients who
      had normal glucose tolerance. CONCLUSION: Circulating levels of PCSK9 in the CF
      population are comparable to those in the healthy population. There are no
      associations between PCSK9 levels and either glucose or lipid homeostasis
      parameters. Nevertheless, a statistically significant link was observed between
      PCSK9 and markers of insulin homeostasis, solely in CF patients who presented
      normal glucose tolerance. Further exploration of the relationship between PCSK9
      and insulin homeostasis in CF patients with normal glucose tolerance is
      warranted.

PMID- 28447579
TI  - Glucan phosphate inhibits HMGB-1 release from rat myocardial H9C2 cells in sepsis
      via TLR4/NF-kB signal pathway.
AB  - PURPOSE: The effect of glucan phosphate (GP) on the release of HMGB-1 from rat
      myocardial cells (H9C2) during lipopolysaccharide-induced sepsis, and the
      underlying mechanisms, were investigated. METHODS: H9C2 cells were divided into
      three groups: normal; lipopolysaccharide (LPS) (1 mg/ml LPS); and, LPS+GP (2
      mg/ml GP). Western blot was used to determine toll-like receptor 4 (TLR4) levels,
      and electrophoretic mobility-shift assays (EMSA) was used to determine nuclear
      factor-kB (NF-kB) activity 3, 6 and 9 h after treatment. HMGB-1 mRNA levels in
      cultured cells were determined by real-time PCR and supernatant HMGB-1 protein
      levels were evaluated by ELISA at 12, 24, 36 and 48 h after treatment. Following
      the transfection of H9C2 cells with Ad5-IkBalpha, which inhibits NF-kB activity,
      TLR4, NF-kB and HMGB-1 levels were determined. RESULTS: Intracellular TLR4 levels
      and NF-kB activity in LPS and LPS+GP groups increased 3-9 h after stimulation,
      but the increased levels of TLR4 and elevated activity of NF-kB were
      significantly lower in the LPS+GP group vs. the LPS group. HMGB-1 mRNA levels in
      both LPS and LPS+GP groups, increased gradually from 24 h after stimulation, but
      the increase was more obvious in the LPS group vs. the LPS+GP group. Supernatant
      HMGB-1 levels in the LPS and LPS+GP groups increased gradually from 9 h after
      stimulation, and also increased markedly in the LPS group. After the inhibition
      of NF-kB activity, LPS-induced HMGB-1 release decreased significantly (p.

PMID- 28447580
TI  - Liver enzyme normalization predicts success of Hepatitis C oral direct-acting
      antiviral treatment.
AB  - PURPOSE: Monitoring of hepatitis C virus (HCV) treatment response is performed by
      serial HCV RNA measurements; however, this may not be useful for predicting
      treatment success or failure with oral direct-acting antiviral agent (DAA)
      therapies. Liver enzyme levels, which are elevated in chronic HCV and tend to
      decline on therapy, may serve as a more logistically and economically feasible
      alternative for monitoring treatment response. SOURCE: The Ottawa Hospital Viral
      Hepatitis Clinic patients (n=219), receiving interferon-free oral DAA treatments,
      were assessed for liver enzymes and HCV RNA levels at baseline, week 4 and >=12
      weeks post-treatment. Suppression cut points used for this analysis were ALT <=
      40U L-1 and AST <= 30U L-1. The primary outcome was week 12 sustained virologic
      response (SVR). By our analysis, all indicators had strong PPV (>90%) but limited
      NPV (.

PMID- 28447581
TI  - Effect of cisplatin-based neoadjuvant chemotherapy on survival in patients with
      bladder cancer: a meta-analysis.
AB  - PURPOSE: Cisplatin-based neoadjuvant chemotherapy (NAC) has been shown to improve
      survival in patients with muscle-invasive bladder cancer (MIBC) who underwent
      radical cystectomy as compared with patients who underwent surgery alone. It has
      also been suggested as current standard of care in surgically-fit patients with
      MIBC. This meta-analysis assessed the effect of cisplatin-based NAC on survival
      in patients with bladder cancer. SOURCE: PubMed, CENTRAL, and Embase were
      searched until November 22, 2016. Two-arm randomized controlled trials that
      compared cisplatin-based neoadjuvant chemotherapy plus local treatment versus the
      same local treatment without neoadjuvant chemotherapy were selected. Patients
      with histologically-confirmed bladder cancer (adenocarcinoma, transitional, or
      squamous-cell carcinoma) were included. The primary outcome was overall survival
      (OS). PRINCIPAL FINDINGS: Of the 292 articles initially identified, 14 were
      included in the final analysis. Patients in the NAC group had similar OS as the
      local treatment (i.e., radiation therapy or cystectomy) group (pooled hazard
      ratio [HR] = 0.92, 95% confidence interval [CI]: 0.84 to 1.00, P=0.056). No
      difference in progress-free survival between two groups was observed (P=0.725).
      Subgroup analysis showed that OS was similar in patients treated with NAC plus
      radiotherapy or cystectomy compared with patients who received local treatment
      alone. CONCLUSIONS: Platinum-based NAC was associated with similar survival
      benefit as patients undergoing cystectomy and/or radiotherapy. No conclusion can
      be drawn about the optimal platinum-based combination to be used in the
      neoadjuvant setting.

PMID- 28447582
TI  - Training the next generation of Canadian Clinician-Scientists: charting a path to
      success.
AB  - Clinician-scientists are physicians with training in both clinical medicine and
      research that enables them to occupy a unique niche as specialists in basic and
      translational biomedical research. While there is widespread acknowledgement of
      the importance of clinician-scientists in today's landscape of evidence-based
      medical practice, training of clinician-scientists in Canada has been on the
      decline, with fewer opportunities to obtain funding. With the increasing length
      of training and lower financial compensation, fewer medical graduates are
      choosing to pursue such a career. MD-PhD programs, in which trainees receive both
      medical and research training, have the potential to be an important tool in
      training the next generation of clinician-scientists; however, MD-PhD trainees in
      Canada face barriers that include an increase in medical school tuition and a
      decrease in the amount of financial support. We examined the available data on MD
      PhD training in Canada and identified a lack of oversight, a lack of funding and
      poor mentorship as barriers experienced by MD-PhD trainees. Specific
      recommendations are provided to begin the process of addressing these challenges,
      starting with the establishment of an overseeing national body that would track
      long-term outcome data for MD-PhD trainees. This national body could then
      function to implement best practices from individual programs across the country
      and to provide further mentorship and support for early-career physician
      scientists. MD-PhD programs have the potential to address Canada's growing
      shortage of clinician-scientists, and strengthening MD-PhD programs will help to
      effect positive change.

PMID- 28447583
TI  - Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients
      With Heart Failure.
AB  - OBJECTIVES: The study sought to compare the prevalence, clinical correlates and
      prognostic impact of diabetes in Southeast Asian versus white patients with heart
      failure (HF) with preserved or reduced ejection fraction. BACKGROUND: Diabetes
      mellitus is common in HF and is associated with impaired prognosis. Asia is home
      to the majority of the world's diabetic population, yet data on the prevalence
      and clinical significance of diabetes in Asian patients with HF are sparse, and
      no studies have directly compared Asian and white patients. METHODS: Two
      contemporary population-based HF cohorts were combined: from Singapore (n =
      1,002, median [25th to 75th percentile] age 62 [54 to 70] years, 76% men, 19.5%
      obesity) and Sweden (n = 19,537, 77 [68 to 84] years, 60% men, 24.8% obesity).
      The modifying effect of ethnicity on the relationship between diabetes and
      clinical correlates or prognosis (HF hospitalization and all-cause mortality) was
      examined using interaction terms. RESULTS: Diabetes was present in 569 (57%)
      Asian patients versus 4,680 (24%) white patients (p < 0.001). Adjusting for
      clinical covariates, obesity was more strongly associated with diabetes in white
      patients (odds ratio [OR]: 3.45; 95% confidence interval [CI]: 2.86 to 4.17) than
      in Asian patients (OR: 1.82; 95% CI: 1.13 to 2.96; pinteraction = 0.026).
      Diabetes was more strongly associated with increased HF hospitalization and all
      cause mortality in Asian patients (hazard ratio: 1.50; 95% CI: 1.21 to 1.87) than
      in white patients (hazard ratio: 1.29; 95% CI: 1.22 to 1.36; pinteraction =
      0.045). CONCLUSIONS: Diabetes was 3-fold more common in Southeast Asian compared
      to white patients with HF, despite younger age and less obesity, and more
      strongly associated with poor outcomes in Asian patients than white patients.
      These results underscore the importance of ethnicity-tailored aggressive
      strategies to prevent diabetes and its complications.

PMID- 28447584
TI  - Creating an ethics curriculum using a structured framework.

PMID- 28447585
TI  - Metabolic profiles of individuals switched to second-line antiretroviral therapy
      after failing standard first-line therapy for treatment of HIV-1 infection in a
      randomized, controlled trial.
AB  - BACKGROUND: To investigate metabolic changes associated with second-line
      antiretroviral therapy (ART) following virological failure of first-line ART.
      METHODS: SECOND-LINE was an open-label randomized controlled trial. Participants
      were randomized 1:1 to receive ritonavir-boosted lopinavir (LPV/r) with 2-3
      nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTI group) or
      raltegravir (RAL group). 210 participants had a dual energy X-ray absorptiometry
      (DXA)-scan at baseline, week 48 and 96. We categorized participants according to
      second-line ART backbone: thymidine analogue (ta-NRTI) + lamivudine/emtricitabine
      (3[F]TC; ta-NRTI group); tenofovir (TDF)+3(F)TC (TDF group); TDF+ta-NRTI +/
      3(F)TC (TDF+ta-NRTI group); RAL. Changes in fasted total cholesterol (TC), low
      density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)
      cholesterol, TC/HDL-cholesterol ratio, triglycerides and glucose from baseline to
      week 96 were examined. We explored the association between metabolic and DXA
      assessed soft-tissue changes. Linear regression methods were used. RESULTS: We
      analysed 454 participants. Participants in RAL group had greater TC increases, TC
      (adjusted mean difference [aMD]=0.65, 95% CI 0.33, 0.96), LDL-c (aMD=0.38, 95% CI
      0.15, 0.61) and glucose (aMD=0.47, 95% CI -0.01, 0.92) compared to TDF group, and
      had greater increases in TC (aMD=0.65, 95% CI 0.28, 1.03), HDL-c (aMD=0.12, 95%
      CI 0.02, 0.23) and LDL-c (aMD=0.41, 95% CI 0.13, 0.69) compared to TDF+ta-NRTI
      group. TC/HDL ratio and triglycerides increased in all groups without significant
      differences between groups. A 1 kg increase in trunk fat mass was associated with
      an increase in TC. CONCLUSIONS: We observed metabolic changes of limited clinical
      significance in the relatively young population enrolled in this study. However,
      the metabolic changes observed may have greater clinical significance in older
      people living with HIV or those with other concomitant cardiovascular risks.

PMID- 28447586
TI  - Serum vascular endothelial growth factor receptor-3 levels in patients with
      esophageal squamous cell cancer.
AB  - AIM: Esophageal cancer is one of the most aggressive tumors of the
      gastrointestinal tract. In this study, we quantified the serum vascular
      endothelial growth factor-3 (VEGFR-3) expression in patients with esophageal
      squamous cell carcinoma (ESCC) to evaluate the role of VEGFR-3 in ESCC. MATERIALS
      AND METHODS: Ninety five patients with ESCC were studied. Pre-therapy and
      preoperative samples were stored and ELISA was used to designate the
      concentrations of VEGFR-3. RESULTS: The serum values of VEGFR-3 were
      significantly higher in patients with ESCC than in healthy donors (p<0.0001).
      CONCLUSIONS: The results imply a very good sensitivity of VEGFR-3 in ESCC. VEGFR
      3 may be a good diagnostic biomarker for ESCC. KEY WORDS: Biomarker, ESCC, VEGFR
      3.

PMID- 28447587
TI  - Appropriateness of Duplex ultrasound assessment on venous system of the legs: a
      two-month preliminary analysis.
AB  - AIM: The goal of this study is to evaluate the appropriateness to prescribe
      venous ultrasound of lower limbs. MATERIAL OF STUDY: Over a two months period,
      1005 Duplex scans were performed by our Vascular Surgery Unit; out of the total,
      225 exams were conducted on venous system of lower limbs. We retrospectively
      analyzed appropriateness of prescription (according to Lombardy District
      indications), urgency of prescription, time-lapse between application for the
      exams and its execution, positive or negative results, National Health System's
      sustained cost. RESULTS: During the above mentioned period, 87,5% of the exams
      were conducted as normal screening with no urgency characteristics, 61 exams
      (27%) were combined with arterial duplex of the same district. General
      Practitioners' requests accounted for 76,8% while only 9,7% were from vascular
      surgeons. Following indications of appropriateness, 117 exams (52%) were judged
      as appropriate. Combining appropriateness and result (chi2 test) we found that if
      the indication was inappropriate the negative result rate was 90,75%; in the
      group of exams prescribed with an urgent request the rate of appropriateness
      raised to 60,7% of whose 94.1% were pathologically positive. DISCUSSION: There is
      no evidence in Literature about appropriateness of prescription of Duplex
      ultrasound for vascular districts. While Lombardy District recently published
      guidelines for prescription, neither vascular surgeon societies nor National
      Health Service ever provided any indication. CONCLUSION: Nowadays there is
      increasing demand for appropriateness in healthcare. This study delivered such
      significant data to make it a pivotal study for an extended analysis during 2016.
      KEY WORDS: Appropriateness, Vascular Duplex Ultrasound, Venous System.

PMID- 28447588
TI  - Malignant peripheral nerve sheath tumour of the oesophagus Review of the
      literature and report of a case with lymph node and distant metastases.
AB  - : Oesophageal sarcomas are very rare while various histological types have
      occasionally been reported. Malignant Peripheral Nerve Sheath Tumour (MPNST) of
      the oesophagus is an exceedingly rare type of oesophageal sarcoma with only
      thirteen cases previously reported in the world literature. However, it should be
      included in the differential diagnosis of oesophageal neoplasias. Due to the
      small number of reported cases, the information about the biological behaviour of
      this entity is still insufficient. While MPNST is generally considered an
      aggressive type of tumour with high recurrence rates after surgical treatment and
      poor prognosis, previous reports of cases with oesophageal localization have
      recorded satisfactory outcomes overall even with less aggressive therapeutic
      approaches, although a long-term follow-up is lacking. Herein, we present the
      case of a 76-year-old female patient with oesophageal MPNST who presented with
      lymph node and distant metastases at the time of diagnosis, accounting for the
      second time only that this unusual presentation of this extremely uncommon
      disease has been reported. In our case, the course of disease was extremely
      aggressive which resulted in the second recorded death from this entity in the
      literature. The case presentation is followed by an extensive review of the world
      literature for the so far reported cases, aiming to highlight all relevant
      aspects such as demographics, clinical features, diagnostic assessment and
      findings, histological parameters, treatment and prognosis, and extract valuable
      previously unpublished conclusions for this rare entity. KEY WORDS: Lymph node
      metastasis, Malignant Peripheral Nerve Sheath Tumour, Malignant schwannoma,
      Neurogenic sarcoma, Oesophagus, S100.

PMID- 28447589
TI  - Neuroretinal evaluation using optical coherence tomography in patients affected
      by pituitary tumors.
AB  - AIM: To investigate the thickness of the retinal nerve fiber layer (RNFL), the
      ganglion cell layer (GCL), inner plexiform layer (IPL), and choroid thickness
      (CT) in patients with pituitary tumours, microadenoma and macroadenoma, using
      spectral optical coherence tomography (OCT). METHODS: Thirty six patients who had
      micro and macroadenoma, and 34 healthy participants (control group) were included
      in the study. Spectral OCT was used to measure the RNFL, GCL, IPL, and CT values
      for all patients. CT measurements were performed by the same author (A.S.K).
      Additionally, retinal nerve fiber length, which is a sublayer of ganglion cell
      complex (GCC), was also measured for each patient and after segmentation oF GCC.
      RESULTS: No difference was detected between group according to sociodemographic
      data. The mean age of patients and the control group was 34.31 +/- 12.47 and
      33.12 +/- 11.75 years, respectively. In the patient group had RNFL thinning while
      there was a thickening of the choroid layer. When all pituitary tumours patients
      (without grouping) were compared with the control group and there were
      significant differences on all parameters: RNFL, GCL, IPL thickness, and CT
      (p<0.05), while there were no significant differences in RNFL and GCL
      measurements between microadenoma and macroadenoma (p>0.05). All patients were
      significantly different from one another with respect to CT (p<0.05).
      CONCLUSIONS: These findings suggest that neurodegeneration occurs in the course
      of pituitary tumours, and this degeneration may be presented by decreased GCL at
      early stages, and as the disease progresses it may also affect ather layers of
      GCC like RNFL and IPL. RNFL and GCL were significantly thinner in the all
      patients as compared with the control subjects. In pituitary tumours, both
      microadenoma and macroadenoma, when evaluating ophthalmological findings
      patients' choroid thinning should be considered. KEY WORDS: Choroid thickness
      Ganglion cell layer thickness, Optical coherence tomographyl Pituitary tumours,
      Retinal nerve fiber layer thickness.

PMID- 28447590
TI  - Concomitant thyroid cancer in patients with primary hyperparathyroidism in an
      endemic goitre region.
AB  - OBJECTIVE: Primary hyperparathyroidism (pHPT) is often accompanied by underlying
      thyroid pathology and 1 to 36% of these thyroid pathologies are malignant. How
      the identification of these lesions affects patient management is unclear. We
      present a single-center experience with the prevalence of concomitant thyroid
      cancer in patients who underwent parathyroidectomy for pHPT. MATERIALS AND
      METHODS: This was a retrospective cohort study. Two hundred-two patients with
      primary hyperparathyroidism included study. Demographic data, clinical findings,
      and final histopathological diagnosis were recorded retrospectively. RESULTS:
      Preoperative cervical ultrasound examination revealed co-existent thyroid
      abnormalities in 117 (57.9%) patients. Mean age of these patients was 57.8 +/-
      12.2 years and 88% were female. Sixty-three (53.9%) of the patients with thyroid
      abnormalities, underwent preoperative fine needle aspiration biopsy (FNAB).
      Cytology result was malignant in one (1.6%) patient, benign in 47(85.7%)
      patients, indeterminate in six (9.5%) patients and Hurthle cell neoplasm in two
      (3.2%) patients. Ninety-four (80.3%) of the patients underwent simultaneous
      thyroid surgery. Final pathology of the thyroid specimen was malignant in 26
      (12.9%) patients. Sixteen of the malignant patients had preoperative FNAB.
      Preoperative FNAB result of these patients was malignant in one patient,
      indeterminate in two patients and benign in 13 patients. CONCLUSION: By
      implementing a comprehensive approach to patients with pHPT who present with
      thyroid disease, concomitant pathology may be elucidated preoperatively. But,
      this approach will not facilitate the detection of otherwise unsuspected thyroid
      cancer in an endemic goitre region. KEY WORDS: Cancer, Parathyroid adenoma,
      Parathyroidectomy, Thyroid, Thyroidectomy.

PMID- 28447591
TI  - Non-crystallographic symmetry of liquid metal, flat crystallographic faults and
      polymorph transformation of the M7C3 carbide.
AB  - The fine lamellar fault structure of primary M7C3 carbide particles in the heat
      resistant Fe-Cr-Ni-C alloy of the HP series (0.45C-25Cr-35Ni) in the cast
      condition has been revealed using transmission electron microscopy. The lamellar
      fault structure is regarded as an inheritance of the initial melt structure. A
      one-to-one correspondence between the crystal structures of M7C3, M5C2, M3C and
      M23C6 carbides and constructions of the projective 103 Desargues configuration
      and its subconfigurations is shown. Mutual mapping between 103 Desargues
      subconfigurations determines transformations of the ten-vertex equal-edged
      triangulated clusters appearing as building units of these carbides.

PMID- 28447592
TI  - The phantom derivative method when a structure model is available: about its
      theoretical basis.
AB  - This study clarifies why, in the phantom derivative (PhD) approach, randomly
      created structures can help in refining phases obtained by other methods. For
      this purpose the joint probability distribution of target, model, ancil and
      phantom derivative structure factors and its conditional distributions have been
      studied. Since PhD may use n phantom derivatives, with n >= 1, a more general
      distribution taking into account all the ancil and derivative structure factors
      has been considered, from which the conditional distribution of the target phase
      has been derived. The corresponding conclusive formula contains two components.
      The first is the classical Srinivasan & Ramachandran term, relating the phases of
      the target structure with the model phases. The second arises from the
      combination of two correlations: that between model and derivative (the first is
      a component of the second) and that between derivative and target. The second
      component mathematically codifies the information on the target phase arising
      from model and derivative electron-density maps. The result is new, and explains
      why a random structure, uncorrelated with the target structure, adds useful
      information on the target phases, provided a model structure is known. Some
      experimental tests aimed at checking if the second component really provides
      information on phi (the target phase) were performed; the favourable results
      confirm the correctness of the theoretical calculations and of the corresponding
      analysis.

PMID- 28447593
TI  - Edge-2-transitive trinodal polyhedra and 2-periodic tilings.
AB  - All trinodal, edge-2-transitive polyhedra and 2-periodic tilings are enumerated
      and described. These are of special interest for the design and synthesis of
      materials such as metal-organic polyhedra and frameworks.

PMID- 28447594
TI  - Diffuse single-crystal scattering corrected for molecular form factor effects.
AB  - This paper shows that chemical short-range order in two-component molecular
      crystals can be solved directly by separating the influence of the molecular form
      factor from the diffraction pattern. This novel technique is demonstrated by
      analysing the diffuse scattering of tris-tert-butyl-1,3,5-benzene tricarboxamide.

PMID- 28447595
TI  - Groupoids and labelled quotient graphs: a topological analysis of the modular
      structure in pyroxenes.
AB  - The analysis of the modular structure of pyroxenes, recently discussed in Nespolo
      & Aroyo [Eur. J. Mineral. (2016), 28, 189-203], has been performed on the
      respective labelled quotient graphs (LQGs). It is shown that the structure and
      maximum symmetry of the module, i.e. its layer group, can be determined directly
      from the LQG. Partial symmetry operations between different modules have been
      associated with automorphisms of the quotient graph that may not be consistent
      with net voltages over the respective cycles. These operations have been shown to
      generate the pyroxene groupoid structure.

PMID- 28447596
TI  - On the Penrose and Taylor-Socolar hexagonal tilings.
AB  - The intimate relationship between the Penrose and the Taylor-Socolar tilings is
      studied, within both the context of double hexagon tiles and the algebraic
      context of hierarchical inverse sequences of triangular lattices. This unified
      approach produces both types of tilings together, clarifies their relationship
      and offers straightforward proofs of their basic properties.

PMID- 28447597
TI  - Resonant and non-resonant magnetic scatterings with circularly polarized X-rays:
      magnetic scattering factor and electron density of gadolinium iron garnet.
AB  - Theoretical and experimental studies on resonant magnetic scattering have been
      carried out using circularly polarized X-rays. Polarization dependence of the
      asymmetric ratio between right- and left-handed polarized scattering amplitudes
      has revealed that resonant and non-resonant magnetic scatterings can be observed
      simultaneously. In this study, synchrotron X-ray intensity experiments were
      conducted on Gd iron garnet (GdIG) at the pre-edge of the Fe K absorption edge.
      The asymmetric ratio between circular polarizations exhibited three peaks due to
      the resonant magnetic responses of Fe3+ in the Fe2 (24d) site. These magnetic
      responses are antiparallel and have apparently higher resolution than dispersive
      X-ray magnetic circular dichroism at the pre-edge region; this can be mainly
      attributed to electric dipole transitions from 1s to t2 energy levels of the 3d
      orbitals in the tetrahedral symmetry in an unstable state quenched at higher
      temperature. Resonant magnetic scattering factors f'm were estimated from the
      asymmetric ratios. Fourier analysis was conducted using the intensity differences
      among circularly polarized X-rays at an energy of E = 7.1085 keV. At this energy
      level, the characteristic distribution of magnetic electron density was clearly
      observed. This distribution was interpreted as a spin arrangement of Gd and Fe
      ions in GdIG. Also observed was the presence of hybridization of the magnetic
      electron orbitals as well as of the resonant magnetic Fe3+. The proposed method
      has the potential to be widely used in crystal structure analysis.

PMID- 28447598
TI  - Convex polyhedra with minimum and maximum names.
AB  - The paper reports the combinatorial types of convex n-acra (i.e. n-vertex
      polyhedra) for which the minimum (min.) and maximum (max.) names are attained.
      Hence, min. and max. names can be independently found without generating the
      whole combinatorial variety of convex n-acra (e.g. by the routine recurrence
      Fedorov algorithm) and calculating names for each n-acron.

PMID- 28447602
TI  - Spatial computation of intratumoral T cells correlates with survival of patients
      with pancreatic cancer.
AB  - The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune
      composition remains largely unknown. Desmoplasia is suggested to polarize PDAC
      immunity. Therefore, a comprehensive evaluation of the composition and
      distribution of desmoplastic elements and T-cell infiltration is necessary to
      delineate their roles. Here we develop a novel computational imaging technology
      for the simultaneous evaluation of eight distinct markers, allowing for spatial
      analysis of distinct populations within the same section. We report a
      heterogeneous population of infiltrating T lymphocytes. Spatial distribution of
      cytotoxic T cells in proximity to cancer cells correlates with increased overall
      patient survival. Collagen-I and alphaSMA+ fibroblasts do not correlate with
      paucity in T-cell accumulation, suggesting that PDAC desmoplasia may not be a
      simple physical barrier. Further exploration of this technology may improve our
      understanding of how specific stromal composition could impact T-cell activity,
      with potential impact on the optimization of immune-modulatory therapies.

PMID- 28447603
TI  - Efficient self-emulsification via cooling-heating cycles.
AB  - In self-emulsification higher-energy micrometre and sub-micrometre oil droplets
      are spontaneously produced from larger ones and only a few such methods are
      known. They usually involve a one-time reduction in oil solubility in the
      continuous medium via changing temperature or solvents or a phase inversion in
      which the preferred curvature of the interfacial surfactant layer changes its
      sign. Here we harness narrow-range temperature cycling to cause repeated breakup
      of droplets to higher-energy states. We describe three drop breakup mechanisms
      that lead the drops to burst spontaneously into thousands of smaller droplets.
      One of these mechanisms includes the remarkable phenomenon of lipid crystal
      dewetting from its own melt. The method works with various oil-surfactant
      combinations and has several important advantages. It enables low surfactant
      emulsion formulations with temperature-sensitive compounds, is scalable to
      industrial emulsification and applicable to fabricating particulate drug carriers
      with desired size and shape.

PMID- 28447604
TI  - Wearable smart sensor systems integrated on soft contact lenses for wireless
      ocular diagnostics.
AB  - Wearable contact lenses which can monitor physiological parameters have attracted
      substantial interests due to the capability of direct detection of biomarkers
      contained in body fluids. However, previously reported contact lens sensors can
      only monitor a single analyte at a time. Furthermore, such ocular contact lenses
      generally obstruct the field of vision of the subject. Here, we developed a
      multifunctional contact lens sensor that alleviates some of these limitations
      since it was developed on an actual ocular contact lens. It was also designed to
      monitor glucose within tears, as well as intraocular pressure using the
      resistance and capacitance of the electronic device. Furthermore, in-vivo and in
      vitro tests using a live rabbit and bovine eyeball demonstrated its reliable
      operation. Our developed contact lens sensor can measure the glucose level in
      tear fluid and intraocular pressure simultaneously but yet independently based on
      different electrical responses.

PMID- 28447605
TI  - Traumatic spinal cord injury.
AB  - Traumatic spinal cord injury (SCI) has devastating consequences for the physical,
      social and vocational well-being of patients. The demographic of SCIs is shifting
      such that an increasing proportion of older individuals are being affected.
      Pathophysiologically, the initial mechanical trauma (the primary injury)
      permeabilizes neurons and glia and initiates a secondary injury cascade that
      leads to progressive cell death and spinal cord damage over the subsequent weeks.
      Over time, the lesion remodels and is composed of cystic cavitations and a glial
      scar, both of which potently inhibit regeneration. Several animal models and
      complementary behavioural tests of SCI have been developed to mimic this
      pathological process and form the basis for the development of preclinical and
      translational neuroprotective and neuroregenerative strategies. Diagnosis
      requires a thorough patient history, standardized neurological physical
      examination and radiographic imaging of the spinal cord. Following diagnosis,
      several interventions need to be rapidly applied, including haemodynamic
      monitoring in the intensive care unit, early surgical decompression, blood
      pressure augmentation and, potentially, the administration of methylprednisolone.
      Managing the complications of SCI, such as bowel and bladder dysfunction, the
      formation of pressure sores and infections, is key to address all facets of the
      patient's injury experience.

PMID- 28447606
TI  - A tunable high-pass filter for simple and inexpensive size-segregation of sub-10
      nm nanoparticles.
AB  - Recent advanced in the fields of nanotechnology and atmospheric sciences
      underline the increasing need for sizing sub-10-nm aerosol particles in a simple
      yet efficient way. In this article, we develop, experimentally test and model the
      performance of a High-Pass Electrical Mobility Filter (HP-EMF) that can be used
      for sizing nanoparticles suspended in gaseous media. Experimental measurements of
      the penetration of nanoparticles having diameters down to ca 1nm through the HP
      EMF are compared with predictions by an analytic, a semi-empirical and a
      numerical model. The results show that the HP-EMF effectively filters
      nanoparticles below a threshold diameter with an extremely high level of sizing
      performance, while it is easier to use compared to existing nanoparticle sizing
      techniques through design simplifications. What is more, the HP-EMF is an
      inexpensive and compact tool, making it an enabling technology for a variety of
      applications ranging from nanomaterial synthesis to distributed monitoring of
      atmospheric nanoparticles.

PMID- 28447607
TI  - Genome-wide identification, characterization, and expression profile of aquaporin
      gene family in flax (Linum usitatissimum).
AB  - Membrane intrinsic proteins (MIPs) form transmembrane channels and facilitate
      transport of myriad substrates across the cell membrane in many organisms.
      Majority of plant MIPs have water transporting ability and are commonly referred
      as aquaporins (AQPs). In the present study, we identified aquaporin coding genes
      in flax by genome-wide analysis, their structure, function and expression pattern
      by pan-genome exploration. Cross-genera phylogenetic analysis with known
      aquaporins from rice, arabidopsis, and poplar showed five subgroups of flax
      aquaporins representing 16 plasma membrane intrinsic proteins (PIPs), 17
      tonoplast intrinsic proteins (TIPs), 13 NOD26-like intrinsic proteins (NIPs), 2
      small basic intrinsic proteins (SIPs), and 3 uncharacterized intrinsic proteins
      (XIPs). Amongst aquaporins, PIPs contained hydrophilic aromatic arginine (ar/R)
      selective filter but TIP, NIP, SIP and XIP subfamilies mostly contained
      hydrophobic ar/R selective filter. Analysis of RNA-seq and microarray data
      revealed high expression of PIPs in multiple tissues, low expression of NIPs, and
      seed specific expression of TIP3 in flax. Exploration of aquaporin homologs in
      three closely related Linum species bienne, grandiflorum and leonii revealed
      presence of 49, 39 and 19 AQPs, respectively. The genome-wide identification of
      aquaporins, first in flax, provides insight to elucidate their physiological and
      developmental roles in flax.

PMID- 28447608
TI  - Common variants in ZMIZ1 and near NGF confer risk for primary dysmenorrhoea.
AB  - Primary dysmenorrhoea, defined as painful menstrual cramps in the absence of
      pelvic pathology, is a common problem in women of reproductive age. Its aetiology
      and pathophysiology remain largely unknown. Here we performed a two-stage genome
      wide association study and subsequent replication study to identify genetic
      factors associated with primary dysmenorrhoea in a total of 6,770 Chinese
      individuals. Our analysis provided evidence of a significant (P<5 * 10-8)
      association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF. ZMIZ1 has
      previously been associated with several autoimmune diseases, and NGF plays a key
      role in the generation of pain and hyperalgesia and has been associated with
      migraine. These findings provide future directions for research on susceptibility
      mechanisms for primary dysmenorrhoea. Furthermore, our genetic architecture
      analysis provides molecular support for the heritability and polygenic nature of
      this condition.

PMID- 28447609
TI  - Spatial working memory alters the efficacy of input to visual cortex.
AB  - Prefrontal cortex modulates sensory signals in extrastriate visual cortex, in
      part via its direct projections from the frontal eye field (FEF), an area
      involved in selective attention. We find that working memory-related activity is
      a dominant signal within FEF input to visual cortex. Although this signal alone
      does not evoke spiking responses in areas V4 and MT during memory, the gain of
      visual responses in these areas increases, and neuronal receptive fields expand
      and shift towards the remembered location, improving the stimulus representation
      by neuronal populations. These results provide a basis for enhancing the
      representation of working memory targets and implicate persistent FEF activity as
      a basis for the interdependence of working memory and selective attention.

PMID- 28447610
TI  - PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA.
AB  - Chromosomal rearrangements are essential events in the pathogenesis of both
      malignant and nonmalignant disorders, yet the factors affecting their formation
      are incompletely understood. Here we develop a zinc-finger nuclease translocation
      reporter and screen for factors that modulate rearrangements in human cells. We
      identify UBC9 and RAD50 as suppressors and 53BP1, DDB1 and poly(ADP)ribose
      polymerase 3 (PARP3) as promoters of chromosomal rearrangements across human cell
      types. We focus on PARP3 as it is dispensable for murine viability and has
      druggable catalytic activity. We find that PARP3 regulates G quadruplex (G4) DNA
      in response to DNA damage, which suppresses repair by nonhomologous end-joining
      and homologous recombination. Chemical stabilization of G4 DNA in PARP3-/- cells
      leads to widespread DNA double-strand breaks and synthetic lethality. We propose
      a model in which PARP3 suppresses G4 DNA and facilitates DNA repair by multiple
      pathways.

PMID- 28447612
TI  - Distinct molecular cues ensure a robust microtubule-dependent nuclear positioning
      in the Drosophila oocyte.
AB  - Controlling nucleus localization is crucial for a variety of cellular functions.
      In the Drosophila oocyte, nuclear asymmetric positioning is essential for the
      reorganization of the microtubule (MT) network that controls the polarized
      transport of axis determinants. A combination of quantitative three-dimensional
      live imaging and laser ablation-mediated force analysis reveal that nuclear
      positioning is ensured with an unexpected level of robustness. We show that the
      nucleus is pushed to the oocyte antero-dorsal cortex by MTs and that its
      migration can proceed through distinct tracks. Centrosome-associated MTs favour
      one migratory route. In addition, the MT-associated protein Mud/NuMA that is
      asymmetrically localized in an Asp-dependent manner at the nuclear envelope
      hemisphere where MT nucleation is higher promotes a separate route. Our results
      demonstrate that centrosomes do not provide an obligatory driving force for
      nuclear movement, but together with Mud, contribute to the mechanisms that ensure
      the robustness of asymmetric nuclear positioning.

PMID- 28447613
TI  - Guilty repair sustains cooperation, angry retaliation destroys it.
AB  - Sustained cooperative social interactions are key to successful outcomes in many
      real-world contexts (e.g., climate change and energy conservation). We explore
      the self-regulatory roles of anger and guilt, as well as prosocial or selfish
      social preferences in a repeated social dilemma game framed around shared
      electricity use at home. We explore the proposal that for sustained cooperation,
      guilty repair needs to override angry retaliation. We show that anger is damaging
      to cooperation as it leads to retaliation and an increase of defection, while,
      through guilt, cooperation is repaired resulting in higher levels of cooperation.
      We demonstrate a disconnect between the experience of anger and subsequent
      retaliation which is a function of participants' social preferences. While there
      is no difference in reports of anger between prosocial and selfish individuals
      after finding out that others use more energy from the communal resource,
      prosocials are less likely to act on their anger and retaliate. Selfish
      individuals are motivated by anger to retaliate but not motivated by guilt to
      repair and contribute disproportionately to the breakdown of cooperation over
      repeated interactions. We suggest that guilt is a key emotion to appeal to when
      encouraging cooperation.

PMID- 28447615
TI  - Millions of Boreal Shield Lakes can be used to Probe Archaean Ocean
      Biogeochemistry.
AB  - Life originated in Archaean oceans, almost 4 billion years ago, in the absence of
      oxygen and the presence of high dissolved iron concentrations. Early Earth
      oxidation is marked globally by extensive banded iron formations but the
      contributing processes and timing remain controversial. Very few aquatic habitats
      have been discovered that match key physico-chemical parameters of the early
      Archaean Ocean. All previous whole ecosystem Archaean analogue studies have been
      confined to rare, low sulfur, and permanently stratified lakes. Here we provide
      first evidence that millions of Boreal Shield lakes with natural anoxia offer the
      opportunity to constrain biogeochemical and microbiological aspects of early
      Archaean life. Specifically, we combined novel isotopic signatures and nucleic
      acid sequence data to examine processes in the anoxic zone of stratified boreal
      lakes that are naturally low in sulfur and rich in ferrous iron, hallmark
      characteristics predicted for the Archaean Ocean. Anoxygenic photosynthesis was
      prominent in total water column biogeochemistry, marked by distinctive patterns
      in natural abundance isotopes of carbon, nitrogen, and iron. These processes are
      robust, returning reproducibly after water column re-oxygenation following lake
      turnover. Evidence of coupled iron oxidation, iron reduction, and methane
      oxidation affect current paradigms of both early Earth and modern aquatic
      ecosystems.

PMID- 28447614
TI  - Cell-size dependent progression of the cell cycle creates homeostasis and
      flexibility of plant cell size.
AB  - Mean cell size at division is generally constant for specific conditions and cell
      types, but the mechanisms coupling cell growth and cell cycle control with cell
      size regulation are poorly understood in intact tissues. Here we show that the
      continuously dividing fields of cells within the shoot apical meristem of
      Arabidopsis show dynamic regulation of mean cell size dependent on developmental
      stage, genotype and environmental signals. We show cell size at division and cell
      cycle length is effectively predicted using a two-stage cell cycle model linking
      cell growth and two sequential cyclin dependent kinase (CDK) activities, and
      experimental results concur in showing that progression through both G1/S and
      G2/M is size dependent. This work shows that cell-autonomous co-ordination of
      cell growth and cell division previously observed in unicellular organisms also
      exists in intact plant tissues, and that cell size may be an emergent rather than
      directly determined property of cells.

PMID- 28447616
TI  - High-order harmonics measured by the photon statistics of the infrared driving
      field exiting the atomic medium.
AB  - High-order harmonics in the extreme-ultraviolet spectral range, resulting from
      the strong-field laser-atom interaction, have been used in a broad range of
      fascinating applications in all states of matter. In the majority of these
      studies the harmonic generation process is described using semi-classical
      theories which treat the electromagnetic field of the driving laser pulse
      classically without taking into account its quantum nature. In addition, for the
      measurement of the generated harmonics, all the experiments require diagnostics
      in the extreme-ultraviolet spectral region. Here by treating the driving laser
      field quantum mechanically we reveal the quantum-optical nature of the high-order
      harmonic generation process by measuring the photon number distribution of the
      infrared light exiting the harmonic generation medium. It is found that the high
      order harmonics are imprinted in the photon number distribution of the infrared
      light and can be recorded without the need of a spectrometer in the extreme
      ultraviolet.

PMID- 28447617
TI  - Corrigendum: Screening with an NMNAT2-MSD platform identifies small molecules
      that modulate NMNAT2 levels in cortical neurons.

PMID- 28447618
TI  - Manufacturing Differences Affect Human Bone Marrow Stromal Cell Characteristics
      and Function: Comparison of Production Methods and Products from Multiple
      Centers.
AB  - Human bone marrow stromal cells (BMSCs, also known as bone marrow-derived
      mesenchymal stem cells) are manufactured using many different methods, but little
      is known about the spectrum of manufacturing methods used and their effects on
      BMSC characteristics and function. Seven centers using, and one developing, Good
      Manufacturing Practices (GMP) processes were surveyed as to their production
      methods. Among the seven centers, all used marrow aspirates as the starting
      material, but no two centers used the same manufacturing methods. Two to four
      BMSC lots from each center were compared using global gene expression. Among the
      twenty-four BMSC lots from the eight centers intra-center transcriptome
      variability was low and similar among centers. Principal component analysis and
      unsupervised hierarchical clustering analysis separated all the lots from five
      centers into five distinct clusters. BMSCs from six of the eight centers were
      tested for their ability to form bone and support hematopoiesis by in vivo
      transplantation (defining features of BMSCs). Those from all six centers tested
      formed bone, but the quantity formed was highly variable and BMSCs from only
      three centers supported hematopoiesis. These results show that differences in
      manufacturing resulted in variable BMSC characteristics including their ability
      to form bone and support hematopoiesis.

PMID- 28447619
TI  - Little Cigars are More Toxic than Cigarettes and Uniquely Change the Airway Gene
      and Protein Expression.
AB  - Little cigars (LCs) are regulated differently than cigarettes, allowing them to
      be potentially targeted at youth/young adults. We exposed human bronchial
      epithelial cultures (HBECs) to air or whole tobacco smoke from cigarettes vs.
      LCs. Chronic smoke exposure increased the number of dead cells, lactate
      dehydrogenase release, and interleukin-8 (IL-8) secretion and decreased apical
      cilia, cystic fibrosis transmembrane conductance regulator (CFTR) protein levels,
      and transepithelial resistance. These adverse effects were significantly greater
      in LC-exposed HBECs than cigarette exposed cultures. LC-exposure also elicited
      unique gene expression changes and altered the proteomic profiles of airway
      apical secretions compared to cigarette-exposed HBECs. Gas chromatography-mass
      spectrometry (GC-MS) analysis indicated that LCs produced more chemicals than
      cigarettes, suggesting that the increased chemical load of LCs may be the cause
      of the greater toxicity. This is the first study of the biological effects of LCs
      on pulmonary epithelia and our observations strongly suggest that LCs pose a more
      severe danger to human health than cigarettes.

PMID- 28447620
TI  - DNA replication licensing factor Cdc6 and Plk4 kinase antagonistically regulate
      centrosome duplication via Sas-6.
AB  - Centrosome number is tightly controlled during the cell cycle to ensure proper
      spindle assembly and cell division. However, the underlying mechanism that
      controls centrosome number remains largely unclear. We show herein that the DNA
      replication licensing factor Cdc6 is recruited to the proximal side of the
      centrioles via cyclin A to negatively regulate centrosome duplication by binding
      and inhibiting the cartwheel protein Sas-6 from forming a stable complex with
      another centriole duplication core protein, STIL. We further demonstrate that
      Cdc6 colocalizes with Plk4 at the centrosome, and interacts with Plk4 during S
      phase. Plk4 disrupts the interaction between Sas-6 and Cdc6, and suppresses the
      inhibitory role of Cdc6 on Sas-6 by phosphorylating Cdc6. Overexpressing wild
      type Cdc6 or Plk4-unphosphorylatable Cdc6 mutant 2A reduces centrosome over
      duplication caused by Plk4 overexpression or hydroxyurea treatment. Taken
      together, our data demonstrate that Cdc6 and Plk4 antagonistically control proper
      centrosome duplication during the cell cycle.

PMID- 28447621
TI  - Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible
      Relevance for Mood Disorders.
AB  - Oxytocin (OXT), synthesized in the hypothalamic paraventricular nucleus (PVN) and
      then released into different brain areas, may play a crucial role in various
      behaviors and neuropsychiatric disorders, including depression. Testosterone has
      been proposed by clinical studies to have the opposite effect of oxytocin in
      these disorders. We began by studying, in the postmortem hypothalamus of fifteen
      patients with mood disorders and fifteen matched controls, the expression of OXT
      in the PVN by means of immunocytochemistry (ICC) and the co-localization of OXT
      and androgen receptor (AR) by means of double labeling ICC. Subsequently, the
      regulatory effect of AR on OXT gene expression was studied in vitro. We found a
      higher expression of PVN OXT in the mood disorder patients than in the control
      subjects, and observed a clear co-localization of AR in OXT-expressing neurons,
      both in the cytoplasm and in the nucleus. In addition, a significant decrease in
      OXT-mRNA levels was observed after pre-incubation of the SK-N-SH cells with
      testosterone. A further potential androgen-responsive element in the human OXT
      gene promotor was revealed by electrophoretic mobility shift assays and co
      transfections in neuroblastoma cells. Finally, in vitro studies demonstrated that
      AR mediated the down-regulation of OXT gene expression. These results suggest
      that the fact that OXT and testosterone appear to have opposite effects in
      neuropsychiatric disorders might be based upon a direct inhibition of AR on OXT
      transcription, which may provide a novel target for therapeutic strategies in
      depression.

PMID- 28447623
TI  - Five low energy phosphorene allotropes constructed through gene segments
      recombination.
AB  - Based on the crystal structures of the previously proposed low energy eta-P and
      theta-P, five new phosphorene allotropes were predicted through gene segments
      recombination method. These five new phosphorene allotropes are confirmed
      dynamically stable and energetically more favorable than their parents (eta-P and
      theta-P). Especially, the XX-XX type G1-P is confirmed energetically more
      favorable than most of all the previously proposed phosphorene allotropes,
      including black phosphorene and blue phosphorene, which is highly expected to be
      synthesized in future experiment through vapor deposition or epitaxial growth
      method like blue beta-P. The calculated results also show that such a new
      promising phosphorene allotrope G1-P is a potential candidate for application in
      nano-electronics according to its middle band gap of about 1.491 eV from DFT
      HSE06 calculation.

PMID- 28447622
TI  - Modern Clinical Research on LSD.
AB  - All modern clinical studies using the classic hallucinogen lysergic acid
      diethylamide (LSD) in healthy subjects or patients in the last 25 years are
      reviewed herein. There were five recent studies in healthy participants and one
      in patients. In a controlled setting, LSD acutely induced bliss, audiovisual
      synesthesia, altered meaning of perceptions, derealization, depersonalization,
      and mystical experiences. These subjective effects of LSD were mediated by the 5
      HT2A receptor. LSD increased feelings of closeness to others, openness, trust,
      and suggestibility. LSD impaired the recognition of sad and fearful faces,
      reduced left amygdala reactivity to fearful faces, and enhanced emotional
      empathy. LSD increased the emotional response to music and the meaning of music.
      LSD acutely produced deficits in sensorimotor gating, similar to observations in
      schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma
      cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic
      resonance studies showed that LSD acutely reduced the integrity of functional
      brain networks and increased connectivity between networks that normally are more
      dissociated. LSD increased functional thalamocortical connectivity and functional
      connectivity of the primary visual cortex with other brain areas. The latter
      effect was correlated with subjective hallucinations. LSD acutely induced global
      increases in brain entropy that were associated with greater trait openness 14
      days later. In patients with anxiety associated with life-threatening disease,
      anxiety was reduced for 2 months after two doses of LSD. In medical settings, no
      complications of LSD administration were observed. These data should contribute
      to further investigations of the therapeutic potential of LSD in psychiatry.

PMID- 28447624
TI  - Wireless Power Transfer to Millimeter-Sized Gastrointestinal Electronics
      Validated in a Swine Model.
AB  - Electronic devices placed in the gastrointestinal (GI) tract for prolonged
      periods have the potential to transform clinical evaluation and treatment. One
      challenge to the deployment of such gastroresident electronics is the difficulty
      in powering millimeter-sized electronics devices without using batteries, which
      compromise biocompatibility and long-term residence. We examined the feasibility
      of leveraging mid-field wireless powering to transfer power from outside of the
      body to electronics at various locations along the GI tract. Using simulations
      and ex vivo measurements, we designed mid-field antennas capable of operating
      efficiently in tissue at 1.2 GHz. These antennas were then characterized in vivo
      in five anesthetized pigs, by placing one antenna outside the body, and the other
      antenna inside the body endoscopically, at the esophagus, stomach, and colon.
      Across the animals tested, mean transmission efficiencies of -41.2, -36.1, and 
      34.6 dB were achieved in vivo while coupling power from outside the body to the
      esophagus, stomach, and colon, respectively. This corresponds to power levels of
      37.5 MUW, 123 MUW and 173 MUW received by antennas in the respective locations,
      while keeping radiation exposure levels below safety thresholds. These power
      levels are sufficient to wirelessly power a range of medical devices from outside
      of the body.

PMID- 28447625
TI  - Randomised, double-blind, placebo-controlled, assessment of the efficacy and
      safety of dietary supplements in prehypertension.
AB  - We aimed to evaluate efficacy and tolerability of a protocol including lifestyle
      modifications and a novel combination of dietary supplements in prehypertension.
      A prospective, double-blind, randomised, placebo-controlled trial was conducted
      in 176 subjects (103 men, aged 52+/-10 years), with blood pressure (BP) of 130
      139 mm Hg systolic and/or 85-89 mm Hg diastolic entered. After a single-blind run
      in period, participants were randomised to twice daily placebo (n=88) or a
      commercially available combination pill (n=88). Primary endpoints were the
      differences in clinic BP between the two groups at the end of the trial.
      Secondary endpoints included intragroup differences in clinic BP during the study
      period and response rates (that is, BP <130/85 mm Hg or a BP reduction >5 mm Hg
      on week 12). Baseline characteristics were similar among the treatment groups. At
      12 weeks, the supplement group had lower systolic BP (124+/-9 versus 132+/-7 mm
      Hg, P<0.0001) and similar diastolic BP (81+/-8 versus 82+/-7 mm Hg, P=0.382)
      compared to the placebo group. With respect to baseline measures, changes in BP
      with supplements were statistically significant for systolic (-9.3+/-4.2 mm Hg,
      P<0.0001) and diastolic values (-4.2+/-3.6 mm Hg, P<0.0001). Changes versus
      baseline in systolic and diastolic BP, conversely, were not different on placebo.
      The overall response rate at week 12 was significantly greater with supplements
      than placebo (58% (51 of 88) and 25% (22 of 88), respectively, P<0.0001). This
      randomised trial shows that combination of supplements with BP-lowering effect is
      an effective additional treatment to conventional lifestyle modifications for a
      better control of systolic BP in prehypertension.

PMID- 28447626
TI  - Familial hyperaldosteronism type III.
AB  - Primary aldosteronism is the most common form of endocrine hypertension. This
      disorder comprises both sporadic and familial forms. Four familial forms of
      primary aldosteronism (FH-I to FH-IV) have been described. FH-III is caused by
      germline mutations in KCNJ5, encoding the potassium channel Kir3.4 (also called
      GIRK4). These mutations alter the selectivity filter of the channel and lead to
      abnormal ion currents with loss of potassium selectivity, sodium influx and
      consequent increased intracellular calcium that causes excessive aldosterone
      biosynthesis. To date, eleven families have been reported, carrying six different
      mutations. Although the clinical features are variable, FH-III patients often
      display severe hyperaldosteronism with an early onset, associated with
      hypokalemia and diabetes insipidus-like symptoms. In most cases FH-III patients
      are resistant to pharmacological therapy and require bilateral adrenalectomy to
      control symptoms. In the present manuscript, we review the genetics and
      pathological basis of FH-III, the diagnostic work-up, clinical features and
      therapeutic management. Finally, we will describe a new case of FH-III of an
      Italian patient carrying a Gly151Arg mutation.

PMID- 28447627
TI  - Short-term blood pressure variability and long-term blood pressure variability:
      which one is a reliable predictor for recurrent stroke.
AB  - The relationship between blood pressure variability (BPV) and stroke recurrence
      is controversial. This study aimed to evaluate the predictive value of short-term
      and long-term BPV for stroke recurrence. The data from blood pressure and
      clinical outcome in TIA or ischemic stroke (BOSS) study included participants
      with acute ischemic stroke or transient ischemic attack (TIA) within 7 days after
      onset. Short-term BPV was measured by 24-h ambulatory BP measurement during
      hospitalisation. Long-term BPV, based on home blood pressure measurement, was
      measured by patients or their families from discharge to 90 days after qualifying
      events onset (twice daily). Variability for systolic blood pressure (SBP) was
      assessed as the s.d., coefficients of variance (CV). The clinical outcome was
      recurrent stroke within 1 year. Cox proportional hazards models were used to test
      the association of short-term BPV, long-term BPV and stroke recurrence. Among
      1764 participants, the mean age was 62.45+/-10.99 years, and 32.1% were females,
      during 1-year follow-up, 106 (6.0%) participants experienced recurrent stroke.
      Indices of long-term BPV were significantly associated with stroke recurrence
      (s.d.: adjusted HR: 1.939, 95% CI: 1.122-3.351; CV: adjusted HR 1.955, 95% CI:
      1.174-3.255), independent of mean SBP. However, all indices of short-term BPV
      (s.d., CV) were not associated with stroke recurrence (s.d.: adjusted HR: 1.245,
      95% CI: 0.680-2.280; CV: adjusted HR: 1.142, 95% CI: 0.640-2.038). In conclusion,
      long-term variation of SBP is a better predictor than short-term variation of SBP
      for recurrent stroke after acute ischemic stroke or TIA.

PMID- 28447628
TI  - The association between inflammation, obesity and elevated blood pressure in 16
      25-year-old females.
AB  - There is evidence to show an association between inflammation, obesity and
      elevated blood pressure. However, there is limited data for this relationship in
      adolescent females. We aimed to investigate the association between high
      sensitivity C-reactive protein (hs-CRP) and elevated blood pressure in young
      Australian females. Women aged 16-25 years living in Victoria were randomly
      recruited via targeted Facebook advertising. Socio-demographic information was
      collected via a web-based questionnaire. Anthropometric and blood pressure
      measurements were conducted by trained staff. Hs-CRP was assessed using the
      Abbott Architect assay. The demographic data were collected from 639 females
      (mean +/-s.d. age: 22+/-3). The blood pressure data were available for 502
      participants. Approximately 28% had elevated blood pressure (defined by a blood
      pressure reading ?120-139/80-89 mm Hg for adults and >90th and <95th percentiles
      for age, sex and height for adolescents). Approximately 24% had hs-CRP >3.0 mg l
      1 and 30% were overweight or obese. In multivariable logistic regression
      analyses, obese females (OR: 5.5, 95% CI: 2.4-12.5, P<0.001) were more likely to
      have elevated blood pressure compared with those with a body mass index (BMI) in
      the normal range. Elevated hs-CRP levels were associated with an increased odds
      of elevated blood pressure (OR: 3.4, 95% CI: 1.8-6.3, P<0.001). However, this
      association was no longer significant after adjustment for BMI. Findings from
      this study demonstrate that hs-CRP and obesity are associated with elevated blood
      pressure in young females. Thus, our findings may promote further research into
      the underlying mechanisms of these associations and related long-term health
      risks.

PMID- 28447629
TI  - Corrigendum: MTH1 inhibition eradicates cancer by preventing sanitation of the
      dNTP pool.

PMID- 28447630
TI  - Plant science: Genomic compartments in barley.

PMID- 28447632
TI  - A universal model for solar eruptions.
AB  - Magnetically driven eruptions on the Sun, from stellar-scale coronal mass
      ejections to small-scale coronal X-ray and extreme-ultraviolet jets, have
      frequently been observed to involve the ejection of the highly stressed magnetic
      flux of a filament. Theoretically, these two phenomena have been thought to arise
      through very different mechanisms: coronal mass ejections from an ideal (non
      dissipative) process, whereby the energy release does not require a change in the
      magnetic topology, as in the kink or torus instability; and coronal jets from a
      resistive process involving magnetic reconnection. However, it was recently
      concluded from new observations that all coronal jets are driven by filament
      ejection, just like large mass ejections. This suggests that the two phenomena
      have physically identical origin and hence that a single mechanism may be
      responsible, that is, either mass ejections arise from reconnection, or jets
      arise from an ideal instability. Here we report simulations of a coronal jet
      driven by filament ejection, whereby a region of highly sheared magnetic field
      near the solar surface becomes unstable and erupts. The results show that
      magnetic reconnection causes the energy release via 'magnetic breakout'-a
      positive-feedback mechanism between filament ejection and reconnection. We
      conclude that if coronal mass ejections and jets are indeed of physically
      identical origin (although on different spatial scales) then magnetic
      reconnection (rather than an ideal process) must also underlie mass ejections,
      and that magnetic breakout is a universal model for solar eruptions.

PMID- 28447633
TI  - Archaeology: Unexpectedly early signs of Americans.

PMID- 28447634
TI  - Correction.

PMID- 28447636
TI  - Environment: An old clue to the secret of longevity.

PMID- 28447637
TI  - Neurosurgery: Gentler alternatives to chips in the brain.

PMID- 28447638
TI  - Commerce: Help bigger palm oil yields to save land.

PMID- 28447639
TI  - Frequency of extreme Sahelian storms tripled since 1982 in satellite
      observations.
AB  - The hydrological cycle is expected to intensify under global warming, with
      studies reporting more frequent extreme rain events in many regions of the world,
      and predicting increases in future flood frequency. Such early, predominantly mid
      latitude observations are essential because of shortcomings within climate models
      in their depiction of convective rainfall. A globally important group of intense
      storms-mesoscale convective systems (MCSs)-poses a particular challenge, because
      they organize dynamically on spatial scales that cannot be resolved by
      conventional climate models. Here, we use 35 years of satellite observations from
      the West African Sahel to reveal a persistent increase in the frequency of the
      most intense MCSs. Sahelian storms are some of the most powerful on the planet,
      and rain gauges in this region have recorded a rise in 'extreme' daily rainfall
      totals. We find that intense MCS frequency is only weakly related to the
      multidecadal recovery of Sahel annual rainfall, but is highly correlated with
      global land temperatures. Analysis of trends across Africa reveals that MCS
      intensification is limited to a narrow band south of the Sahara desert. During
      this period, wet-season Sahelian temperatures have not risen, ruling out the
      possibility that rainfall has intensified in response to locally warmer
      conditions. On the other hand, the meridional temperature gradient spanning the
      Sahel has increased in recent decades, consistent with anthropogenic forcing
      driving enhanced Saharan warming. We argue that Saharan warming intensifies
      convection within Sahelian MCSs through increased wind shear and changes to the
      Saharan air layer. The meridional gradient is projected to strengthen throughout
      the twenty-first century, suggesting that the Sahel will experience particularly
      marked increases in extreme rain. The remarkably rapid intensification of
      Sahelian MCSs since the 1980s sheds new light on the response of organized
      tropical convection to global warming, and challenges conventional projections
      made by general circulation models.

PMID- 28447640
TI  - Abrasion-set limits on Himalayan gravel flux.
AB  - Rivers sourced in the Himalayan mountain range carry some of the largest sediment
      loads on the planet, yet coarse gravel in these rivers vanishes within
      approximately 10-40 kilometres on entering the Ganga Plain (the part of the North
      Indian River Plain containing the Ganges River). Understanding the fate of gravel
      is important for forecasting the response of rivers to large influxes of sediment
      triggered by earthquakes or storms. Rapid increase in gravel flux and subsequent
      channel bed aggradation (that is, sediment deposition by a river) following the
      1999 Chi-Chi and 2008 Wenchuan earthquakes reduced channel capacity and increased
      flood inundation. Here we present an analysis of fan geometry, sediment grain
      size and lithology in the Ganga Basin. We find that the gravel fluxes from rivers
      draining the central Himalayan mountains, with upstream catchment areas ranging
      from about 350 to 50,000 square kilometres, are comparable. Our results show that
      abrasion of gravel during fluvial transport can explain this observation; most of
      the gravel sourced more than 100 kilometres upstream is converted into sand by
      the time it reaches the Ganga Plain. These findings indicate that earthquake
      induced sediment pulses sourced from the Greater Himalayas, such as that
      following the 2015 Gorkha earthquake, are unlikely to drive increased gravel
      aggradation at the mountain front. Instead, we suggest that the sediment influx
      should result in an elevated sand flux, leading to distinct patterns of
      aggradation and flood risk in the densely populated, low-relief Ganga Plain.

PMID- 28447635
TI  - A chromosome conformation capture ordered sequence of the barley genome.
AB  - Cereal grasses of the Triticeae tribe have been the major food source in
      temperate regions since the dawn of agriculture. Their large genomes are
      characterized by a high content of repetitive elements and large pericentromeric
      regions that are virtually devoid of meiotic recombination. Here we present a
      high-quality reference genome assembly for barley (Hordeum vulgare L.). We use
      chromosome conformation capture mapping to derive the linear order of sequences
      across the pericentromeric space and to investigate the spatial organization of
      chromatin in the nucleus at megabase resolution. The composition of genes and
      repetitive elements differs between distal and proximal regions. Gene family
      analyses reveal lineage-specific duplications of genes involved in the transport
      of nutrients to developing seeds and the mobilization of carbohydrates in grains.
      We demonstrate the importance of the barley reference sequence for breeding by
      inspecting the genomic partitioning of sequence variation in modern elite
      germplasm, highlighting regions vulnerable to genetic erosion.

PMID- 28447641
TI  - Predatory journals: Beall's List is missed.

PMID- 28447642
TI  - Predatory journals: fortify the defences.

PMID- 28447645
TI  - Atmospheric science: Severe weather in a warming climate.

PMID- 28447646
TI  - A 130,000-year-old archaeological site in southern California, USA.
AB  - The earliest dispersal of humans into North America is a contentious subject, and
      proposed early sites are required to meet the following criteria for acceptance:
      (1) archaeological evidence is found in a clearly defined and undisturbed
      geologic context; (2) age is determined by reliable radiometric dating; (3)
      multiple lines of evidence from interdisciplinary studies provide consistent
      results; and (4) unquestionable artefacts are found in primary context. Here we
      describe the Cerutti Mastodon (CM) site, an archaeological site from the early
      late Pleistocene epoch, where in situ hammerstones and stone anvils occur in
      spatio-temporal association with fragmentary remains of a single mastodon (Mammut
      americanum). The CM site contains spiral-fractured bone and molar fragments,
      indicating that breakage occured while fresh. Several of these fragments also
      preserve evidence of percussion. The occurrence and distribution of bone, molar
      and stone refits suggest that breakage occurred at the site of burial. Five large
      cobbles (hammerstones and anvils) in the CM bone bed display use-wear and impact
      marks, and are hydraulically anomalous relative to the low-energy context of the
      enclosing sandy silt stratum. 230Th/U radiometric analysis of multiple bone
      specimens using diffusion-adsorption-decay dating models indicates a burial date
      of 130.7 +/- 9.4 thousand years ago. These findings confirm the presence of an
      unidentified species of Homo at the CM site during the last interglacial period
      (MIS 5e; early late Pleistocene), indicating that humans with manual dexterity
      and the experiential knowledge to use hammerstones and anvils processed mastodon
      limb bones for marrow extraction and/or raw material for tool production.
      Systematic proboscidean bone reduction, evident at the CM site, fits within a
      broader pattern of Palaeolithic bone percussion technology in Africa, Eurasia and
      North America. The CM site is, to our knowledge, the oldest in situ, well
      documented archaeological site in North America and, as such, substantially
      revises the timing of arrival of Homo into the Americas.

PMID- 28447648
TI  - Microscopy: A larger palette for biological imaging.

PMID- 28447650
TI  - Announcement: Nature journals support the San Francisco Declaration on Research
      Assessment.

PMID- 28447649
TI  - California's $3-billion bet on stem cells faces final test.

PMID- 28447651
TI  - Surprise El Nino causes devastation but offers lessons for ecologists.

PMID- 28447652
TI  - Reviewers are blinkered by bibliometrics.

PMID- 28447653
TI  - The next big hit in molecule Hollywood.

PMID- 28447655
TI  - March for Science, climate engineering and China's space station.

PMID- 28447654
TI  - More surgeons must start doing basic science.

PMID- 28447656
TI  - Mining threatens Chinese fossil site that revealed planet's earliest animals.

PMID- 28447657
TI  - What happened at March for Science events around the world.

PMID- 28447658
TI  - Ripple effects of New Zealand earthquake continue to this day.

PMID- 28447660
TI  - Liquid-biopsies success highlights power of combining basic and clinical
      research.

PMID- 28447659
TI  - Planetariums - not just for kids.

PMID- 28447661
TI  - The nonsystemic vasculitic neuropathies.
AB  - Nonsystemic vasculitic neuropathy (NSVN) is an under-recognized single-organ
      vasculitis of peripheral nerves that can only be diagnosed with a nerve biopsy. A
      Peripheral Nerve Society guideline group published consensus recommendations on
      the classification, diagnosis and treatment of NSVN in 2010, and new diagnostic
      criteria for vasculitic neuropathy were developed by the Brighton Collaboration
      in 2015. In this Review, we provide an update on the classification, diagnosis
      and treatment of NSVN. NSVN subtypes include Wartenberg migratory sensory
      neuropathy and postsurgical inflammatory neuropathy. Variants include diabetic
      radiculoplexus neuropathy and - arguably - neuralgic amyotrophy. NSVN with
      proximal involvement is sometimes termed nondiabetic lumbosacral radiculoplexus
      neuropathy. Cutaneous polyarteritis nodosa and other skin-nerve vasculitides
      overlap with NSVN clinically. Three patterns of involvement in NSVN have been
      identified: multifocal neuropathy, distal symmetric polyneuropathy, and
      overlapping multifocal neuropathy (asymmetric polyneuropathy). These patterns
      lack standard definitions, resulting in inconsistencies between studies. We
      propose definitions and provide an up-to-date differential diagnosis of
      multifocal neuropathy. Available evidence suggests that NSVN and neuropathy
      predominant systemic vasculitis might be controlled better by treatment with
      corticosteroids and an immunosuppressive agent than with corticosteroids alone.
      Treated NSVN rarely spreads to other organs, but 30% of patients experience a
      relapse. Long-term neurological outcome is favourable, but chronic pain is
      common.

PMID- 28447663
TI  - Basic research: Kidneys and cardiac stress.

PMID- 28447662
TI  - Expert consensus document: Echocardiography and lung ultrasonography for the
      assessment and management of acute heart failure.
AB  - Echocardiography is increasingly recommended for the diagnosis and assessment of
      patients with severe cardiac disease, including acute heart failure. Although
      previously considered to be within the realm of cardiologists, the development of
      ultrasonography technology has led to the adoption of echocardiography by acute
      care clinicians across a range of specialties. Data from echocardiography and
      lung ultrasonography can be used to improve diagnostic accuracy, guide and
      monitor the response to interventions, and communicate important prognostic
      information in patients with acute heart failure. However, without the
      appropriate skills and a good understanding of ultrasonography, its wider
      application to the most acutely unwell patients can have substantial pitfalls.
      This Consensus Statement, prepared by the Acute Heart Failure Study Group of the
      ESC Acute Cardiovascular Care Association, reviews the existing and potential
      roles of echocardiography and lung ultrasonography in the assessment and
      management of patients with acute heart failure, highlighting the differences
      from established practice where relevant.

PMID- 28447664
TI  - Efficient design of clinical trials and epidemiological research: is it possible?
AB  - Randomized clinical trials and large-scale, cohort studies continue to have a
      critical role in generating evidence in cardiovascular medicine; however, the
      increasing concern is that ballooning costs threaten the clinical trial
      enterprise. In this Perspectives article, we discuss the changing landscape of
      clinical research, and clinical trials in particular, focusing on reasons for the
      increasing costs and inefficiencies. These reasons include excessively complex
      design, overly restrictive inclusion and exclusion criteria, burdensome
      regulations, excessive source-data verification, and concerns about the effect of
      clinical research conduct on workflow. Thought leaders have called on the
      clinical research community to consider alternative, transformative business
      models, including those models that focus on simplicity and leveraging of digital
      resources. We present some examples of innovative approaches by which some
      investigators have successfully conducted large-scale, clinical trials at
      relatively low cost. These examples include randomized registry trials, cluster
      randomized trials, adaptive trials, and trials that are fully embedded within
      digital clinical care or administrative platforms.

PMID- 28447666
TI  - In situ polymerisation of isoeugenol as a green consolidation method for
      waterlogged archaeological wood.
AB  - Waterlogged archaeological wood is often in need of consolidation prior to drying
      to prevent shrinkage and cracking of the object. There is a need for new greener
      materials (than for example polyethylene glycol) and methods for consolidation to
      be developed. The use of wood-based components could provide good interaction
      between the consolidant and the remaining wood structure and would also support a
      shift away from fossil fuel-based materials to those with more sustainable
      sources. Based on this, lignin-like structures have been investigated for their
      ability to consolidate waterlogged archaeological wood. The in situ formation of
      a lignin-like material has been carried out using isoeugenol polymerised by horse
      radish peroxidase in aqueous solution. The formation of the oligomeric/polymeric
      materials within the wood following this reaction has been determined by
      Attenuated Total Reflectance Fourier Transform Infra Red (ATR-FTIR) spectroscopy.
      The oligomers remaining in solution have been characterised by ATR-FTIR and
      nuclear magnetic resonance (NMR) spectroscopy as well as analytical
      ultracentrifugation, showing that they have a weight average Mw of 0.4-0.9 kDa
      and a lignin-like structure rich in the beta-5' moiety. Therefore, this approach
      is proposed as a basis to further develop a green consolidation method for
      waterlogged archaeological wood.

PMID- 28447665
TI  - Creation of energetic biothermite inks using ferritin liquid protein.
AB  - Energetic liquids function mainly as fuels due to low energy densities and slow
      combustion kinetics. Consequently, these properties can be significantly
      increased through the addition of metal nanomaterials such as aluminium.
      Unfortunately, nanoparticle additives are restricted to low mass fractions in
      liquids because of increased viscosities and severe particle agglomeration.
      Nanoscale protein ionic liquids represent multifunctional solvent systems that
      are well suited to overcoming low mass fractions of nanoparticles, producing
      stable nanoparticle dispersions and simultaneously offering a source of oxidizing
      agents for combustion of reactive nanomaterials. Here, we use iron oxide-loaded
      ferritin proteins to create a stable and highly energetic liquid composed of
      aluminium nanoparticles and ferritin proteins for printing and forming 3D shapes
      and structures. In total, this bioenergetic liquid exhibits increased energy
      output and performance, enhanced dispersion and oxidation stability, lower
      activation temperatures, and greater processability and functionality.

PMID- 28447667
TI  - TWEAK blockade decreases atherosclerotic lesion size and progression through
      suppression of STAT1 signaling in diabetic mice.
AB  - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK/Tnfsf12) is a
      cytokine implicated in different steps associated with vascular remodeling.
      However, the role of TWEAK under hyperglycemic conditions is currently unknown.
      Using two different approaches, genetic deletion of Tnfsf12 and treatment with a
      TWEAK blocking mAb, we have analyzed the effect of TWEAK inhibition on
      atherosclerotic plaque progression and stability in streptozotocin-induced
      diabetic ApoE deficient mice. Genetic inactivation of Tnfsf12 reduced
      atherosclerosis extension and severity in diabetic ApoE deficient mice. Tnfsf12
      deficient mice display a more stable plaque phenotype characterized by lower
      lipid and macrophage content within atherosclerotic plaques. A similar phenotype
      was observed in diabetic mice treated with anti-TWEAK mAb. The proatherosclerotic
      effects of TWEAK were mediated, at least in part, by STAT1 activation and
      expression of proinflammatory target genes (CCL5, CXCL10 and ICAM-1), both in
      plaques of ApoE mice and in cultured vascular smooth muscle cells (VSMCs) under
      hyperglycemic conditions. Loss-of-function experiments demonstrated that TWEAK
      induces proinflammatory genes mRNA expression through its receptor Fn14 and STAT1
      activation in cultured VSMCs. Overall, TWEAK blockade delay plaque progression
      and alter plaque composition in diabetic atherosclerotic mice. Therapies aimed to
      inhibit TWEAK expression and/or function could protect from diabetic vascular
      complications.

PMID- 28447670
TI  - Harmonic trap resonance enhanced synthetic atomic spin-orbit coupling.
AB  - Spin-orbit coupling (SOC) plays an essential role in many exotic and interesting
      phenomena in condensed matter physics. In neutral-atom-based quantum simulations,
      synthetic SOC constitutes a key enabling element. The strength of SOC realized so
      far is limited by various reasons or constraints. This work reports tunable SOC
      synthesized with a gradient magnetic field (GMF) for atoms in a harmonic trap.
      Nearly ten-fold enhancement is observed when the GMF is modulated near the
      harmonic-trap resonance in comparison with the free-space situation. A theory is
      developed that well explains the experimental results. Our work offers a clear
      physical insight into and analytical understanding of how to tune the strength of
      atomic SOC synthesized with GMF using harmonic trap resonance.

PMID- 28447671
TI  - The scaffold microenvironment for stem cell based bone tissue engineering.
AB  - Bone tissue engineering uses the principles and methods of engineering and life
      sciences to study bone structure, function and growth mechanism for the purposes
      of repairing, maintaining and improving damaged bone tissue. Scaffolds not only
      provide structural support for stem cells in cell adhesion and proliferation and
      bone formation, but also serve as a microenvironment for guiding stem cell
      differentiation and tissue regeneration and for controlling tissue structure.
      This review presents the research status of the scaffold microenvironment for
      bone-related stem cells based on bone tissue engineering. Scaffold materials and
      the stem cell microenvironment are described in this review, and the existing
      shortcomings are also simply mentioned.

PMID- 28447672
TI  - From [11C]CO2 to [11C]amides: a rapid one-pot synthesis via the Mitsunobu
      reaction.
AB  - A novel amide synthesis methodology is described using amines, CO2 and Grignard
      reagents and Mitsunobu reagents. The method was applied to carbon-11
      radiochemistry to label amides using cyclotron-produced [11C]CO2. The synthetic
      utility of the one-pot labelling methodology was demonstrated by producing
      [11C]melatonin. The incorporation of [11C]CO2 into [11C]melatonin was 36% -
      determined by radioHPLC 2 min post [11C]CO2 delivery.

PMID- 28447674
TI  - Role of grain size on redox induced compositional stresses in Pr doped ceria thin
      films.
AB  - In constrained geometries and in varying oxygen partial pressures and operating
      temperatures, exchange of oxygen ions between non-stoichiometric oxide thin films
      (for example, doped and undoped ceria systems) and the gas phase can lead to
      stresses. In this study, these compositional stresses were investigated in thin
      films of nanocrystalline 10% praseodymium doped ceria (PCO), as a function of
      average grain size. In situ wafer curvature measurements, along with High
      Temperature X-Ray Diffraction (HTXRD), were employed to measure stresses and
      strains, respectively on the PCO films during oxidation-reduction cycling, over
      the pO2 range of 10-1-10-5 atm at 750  degrees C. For relatively large grain
      sizes, the stress values agree well with the amount of expansion induced by
      oxygen non-stoichiometry (chemical expansion) predicted by a thin film defect
      equilibria model that was developed previously. The compositional stresses were
      found to increase with decreasing grain size. The origin of this effect,
      including the role of space charge effects near surfaces and interfaces are
      discussed in this paper. To our knowledge, this is the first time that such
      comparisons are reported by simultaneously employing high temperature in situ
      wafer curvature and HTXRD measurements on doped ceria systems.

PMID- 28447675
TI  - Back-exchange: a novel approach to quantifying oxygen diffusion and surface
      exchange in ambient atmospheres.
AB  - A novel two-step Isotopic Exchange (IE) technique has been developed to
      investigate the influence of oxygen containing components of ambient air (such as
      H2O and CO2) on the effective surface exchange coefficient (k*) of a common mixed
      ionic electronic conductor material. The two step 'back-exchange' technique was
      used to introduce a tracer diffusion profile, which was subsequently measured
      using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). The isotopic
      fraction of oxygen in a dense sample as a function of distance from the surface,
      before and after the second exchange step, could then be used to determine the
      surface exchange coefficient in each atmosphere. A new analytical solution was
      found to the diffusion equation in a semi-infinite domain with a variable surface
      exchange boundary, for the special case where D* and k* are constant for all
      exchange steps. This solution validated the results of a numerical, Crank
      Nicolson type finite-difference simulation, which was used to extract the
      parameters from the experimental data. When modelling electrodes, D* and k* are
      important input parameters, which significantly impact performance. In this study
      La0.6Sr0.4Co0.2Fe0.8O3-delta (LSCF6428) was investigated and it was found that
      the rate of exchange was increased by around 250% in ambient air compared to high
      purity oxygen at the same pO2. The three experiments performed in this study were
      used to validate the back-exchange approach and show its utility.

PMID- 28447676
TI  - Excited-state E -> Z photoisomerization mechanism unveiled by ab initio
      nonadiabatic molecular dynamics simulation for hemithioindigo-hemistilbene.
AB  - The Zhu-Nakamura formulas based on on-the-fly trajectory surface hopping dynamics
      simulations at the two-state-averaged CASSCF level were employed to investigate
      the E -> Z photoisomerization mechanisms of hemithioindigo-hemistilbene (HTI)
      upon S1 excitation. Seven conical intersections were observed along the
      isomerization pathways, which were composed of double bond torsion, benzene ring
      torsion, inversion and pyramidalization motions, and only three of them were
      found to play a role in the dynamics simulations started at S1E-HTI. The dominant
      isomerization pathway proceeds via central double bond torsion together with
      pyramidal and tilt motions to some extent (hop via CI5) and accounts for all the
      reactive trajectories. On the other hand, the two pathways that involve the
      conical zones lie in the vicinity of the E-form Franck-Condon region (CI7) and
      proceed along the combined central double bond and benzene ring torsion route
      (CI3/CI4) with generation of the E products. Within the 332 simulated
      trajectories, 66 hop to the ground state and only 19 switch to the Z product. The
      estimated quantum yield of 0.057 (19 in 332) agrees well with the reported
      experimental value of 0.053 +/- 0.016. The excited-state lifetimes span a wide
      region from hundreds of femtoseconds to several picoseconds, depending on the
      time for vibrational relaxation and number of cycles for periodical mixed mode
      torsion.

PMID- 28447677
TI  - Investigation of easy-plane magnetic anisotropy in P-ligand square-pyramidal CoII
      single ion magnets.
AB  - In this work we report two pentacoordinated CoII-P4X1 Single Ion Magnets (SIMs)
      based on P-donor ligands. The tetradentate ligand tris[2
      (diphenylphosphino)ethyl]phosphine allows the obtention of the isostructural
      square pyramidal [Co(PP3)Cl].ClO4 (1) and [Co(PP3)Br].ClO4 (2) complexes.
      Consistent theoretical and experimental studies indicate that these complexes
      have a high spin (S = 3/2) ground state and suggest that the relaxation dynamics
      is governed by ground state quantum tunneling, whereas its temperature dependence
      is directed by optical or acoustic Raman processes.

PMID- 28447678
TI  - Metal ions in the synthesis of interlocked molecules and materials.
AB  - The use of metal ions to template the synthesis of catenanes by Sauvage and co
      workers was a pivotal moment in the development of the field of interlocked
      molecules. In this Review Article we shall examine the different roles metal
      ligand interactions play in modern syntheses of interlocked molecules and
      materials, with a particular focus on seminal contributions and the advantages
      and disadvantages of employing metal ligand interactions.

PMID- 28447679
TI  - Isoprene chain shuttling polymerisation between cis and trans regulating
      catalysts: straightforward access to a new material.
AB  - Isoprene chain shuttling polymerisation between the 1,4-trans regulating
      Cp*La(BH4)2(THF)2/MgnBuEt (Cp* = C5Me5) and the 1,4-cis regulating
      NdCl3(THF)2/AlR3 (R = Et or iBu) systems provides access to stereoblock
      polyisoprene. Under selected experimental conditions, the trans segments are semi
      crystalline, leading to a thermoplastic elastomer-like material.

PMID- 28447680
TI  - Subthreshold swing improvement in MoS2 transistors by the negative-capacitance
      effect in a ferroelectric Al-doped-HfO2/HfO2 gate dielectric stack.
AB  - Obtaining a subthreshold swing (SS) below the thermionic limit of 60 mV dec-1 by
      exploiting the negative-capacitance (NC) effect in ferroelectric (FE) materials
      is a novel effective technique to allow the reduction of the supply voltage and
      power consumption in field effect transistors (FETs). At the same time, two
      dimensional layered semiconductors, such as molybdenum disulfide (MoS2), have
      been shown to be promising candidates to replace silicon MOSFETs in sub-5 nm
      channel technology nodes. In this paper, we demonstrate NC MoS2 FETs by
      incorporating a ferroelectric Al-doped HfO2 (Al : HfO2), a technologically
      compatible material, in the FET gate stack. Al : HfO2 thin films were deposited
      on Si wafers by atomic layer deposition. Voltage amplification up to 1.25 times
      was observed in a FE bilayer stack of Al : HfO2/HfO2 with a Ni metallic
      intermediate layer. The minimum SS (SSmin) of the NC-MoS2 FET built on the FE
      bilayer improved to 57 mV dec-1 at room temperature, compared with SSmin = 67 mV
      dec-1 for the MoS2 FET with only HfO2 as a gate dielectric.

PMID- 28447683
TI  - Self-assembled hybrid elastin-like polypeptide/silica nanoparticles enable
      triggered drug release.
AB  - The discovery of biomimetic polypeptides that enable the biomineralization of
      synthetic and biosynthetic materials has resulted in the development of hybrid
      materials that incorporate inorganic components for potential application in drug
      delivery, enzyme immobilization, and surface modification. Here, we describe an
      approach that uses micellar assemblies of an elastin-like polypeptide (ELP)
      modified with silica-promoting sequences and drug conjugates that are
      subsequently encapsulated within a silica matrix. Incorporation of a lysine-rich
      tag derived from the silaffin R5 peptide into the N-terminus of a hydrophilic ELP
      that self-assembles upon conjugation of hydrophobic molecules at the C-terminus
      results in the formation of spherical micelles with a conjugated drug embedded in
      the core and a corona that is decorated with the silaffin peptide. These micelles
      serve as the building blocks for the polycondensation of silica into uniform,
      hybrid polypeptide-silica nanoparticles. We demonstrate proof-of-concept examples
      using a model hydrophobic small molecule and doxorobucin, a small molecule
      chemotherapeutic, and further show pH-dependent doxorubicin release from the
      hybrid nanoparticles.

PMID- 28447668
TI  - Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals
      regulation of TERT by ZNF148.
AB  - Genome wide association studies (GWAS) have mapped multiple independent cancer
      susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic
      and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses
      the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with
      increased pancreatic and testicular but decreased lung cancer and melanoma risk,
      and exhibited preferred protein-binding and enhanced regulatory activity.
      Transcriptional gene silencing of this regulatory element repressed TERT
      expression in an allele-specific manner. Proteomic analysis identifies allele
      preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further
      supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results
      in reduced TERT expression, telomerase activity and telomere length. Our results
      indicate that the association with chr5p15.33-Region 2 may be explained by
      rs36115365, a variant influencing TERT expression via ZNF148 in a manner
      consistent with elevated TERT in carriers of the C allele.

PMID- 28447684
TI  - Crystal structure, NIR luminescence and X-ray computed tomography of
      Nd3+:Ba0.3Lu0.7F2.7 nanospheres.
AB  - Uniform, hydrophilic 50 nm diameter Nd3+-doped Ba0.3Lu0.7F2.7 nanospheres are
      synthesized at 120  degrees C using a singular one-pot method based on the use of
      ethylene glycol as solvent, in the absence of any additive. The composition and
      crystal structure of the undoped material are analyzed in detail using ICP and
      XRD, which reveals a BaF2 cubic crystal structure that is able to incorporate 70
      mol% of Lu ions. This finding contrasts with the reported phase diagram of the
      system, where the maximum solubility is around 30 mol% Lu. XRD proves as well
      that the Ba0.3Lu0.7F2.7 structure is able to incorporate Nd3+ ions up to, at
      least 10 mol%, without altering the uniform particles morphology. The Nd-doped
      particles exhibit near-infrared luminescence when excited at 810 nm. The maximum
      emission intensity with the minimum concentration quenching effect is obtained at
      1.5% Nd doping level. X-ray computed tomography experiments are carried out on
      powder samples of the latter composition. The sample significantly absorbs X-ray
      photons, thus demonstrating that the Nd3+-doped Ba0.3Lu0.7F2.7 nanospheres are
      good candidates as contrast agents in computed tomography.

PMID- 28447685
TI  - Rearrangement of an aniline linked perylene bisimide under acidic conditions and
      visible to near-infrared emission from the intramolecular charge-transfer state
      of its fused derivatives.
AB  - We have prepared a series of aniline-linked and fused perylene bisimides (PBIs)
      for making near-infrared (NIR) fluorophores. During this research, we found an
      unexpected rearrangement reaction on the PBI core for the first time. The aniline
      and phenothiazine-fused PBIs exhibit excellent absorption ability and visible-to
      NIR emission owing to their intramolecular charge transfer character.

PMID- 28447686
TI  - Highly efficient inverted solar cells based on perovskite grown nanostructures
      mediated by CuSCN.
AB  - In this work, three different CuSCN nanostructures (NSs), hexagonal prism-like
      (3D), pyramid-like (2D) and nanowire structures (NWs) are first applied to
      inverted heterojunction perovskite solar cells as p-type inorganic hole transport
      layers (HTLs) using a moderate electrodeposition method at room temperature. It
      is revealed that the crystal structure and the thickness of the CuSCN layer can
      dramatically regulate the morphology and the crystal orientation behavior of
      perovskite absorbing layers, which will further have a significant influence on
      the following device performance. Compared with the other two nanostructured
      CuSCN HTLs, devices based on 3D structured CuSCN HTLs exhibit better performance
      mainly attributed to the high crystalline quality of perovskite films controlled
      by the well-oriented hexagonal prism-like nanostructures of CuSCN. After
      optimization, a maximum power conversion efficiency (PCE) of 11.40% has been
      obtained with 3D CuSCN which has a thickness of 200 nm. It is the highest value
      among the current reports using nanostructured CuSCN as an inorganic HTL in
      inverted PSCs. The dominating effect of CuSCN nanostructures on the crystal
      quality of perovskites provides guidelines for future material optimization and
      device efficiency enhancement.

PMID- 28447687
TI  - Can dual-ligand targeting enhance cellular uptake of nanoparticles?
AB  - Dual ligand targeting to different types of over-expressed receptors on cell
      surfaces is a promising strategy in nanomedicine. Here, by using dissipative
      particle dynamics simulations, the effect of the surface distribution and
      physicochemical properties of dual ligands on the cellular uptake of
      nanoparticles is systematically studied. It is found that the spontaneous
      rearrangement of dual ligands (from random to patterned distribution) on the
      nanoparticle surface can enhance the cellular uptake of nanoparticles. While the
      short length of ligands may restrict the ligand rearrangement, nanoparticles
      coated with short dual ligands cannot be fully wrapped by cell membranes unless
      the dual ligands are initially separated on the nanoparticle surface. Besides,
      when there exists a length mismatch or non-specific interaction between the dual
      ligands, dual-ligand targeting cannot enhance the uptake efficiency, either.
      Further, we also provide the design guidelines for surface decoration, and find
      that the Janus nanoparticle can make the most of dual-ligand targeting. These
      results can help understand how to better use dual ligands to achieve efficient
      cellular uptake, which may provide significant insights into the optimal design
      of future nanomaterials in drug delivery.

PMID- 28447688
TI  - Influence of cosolvents, self-crowding, temperature and pressure on the sub
      nanosecond dynamics and folding stability of lysozyme.
AB  - We studied the effects of temperature and hydrostatic pressure on the dynamical
      properties and folding stability of highly concentrated lysozyme solutions in the
      absence and presence of the osmolytes trimethylamine-N-oxide (TMAO) and urea.
      Elastic incoherent neutron scattering (EINS) was applied to determine the mean
      squared displacement (MSD) of the protein's hydrogen atoms to yield insights into
      the effects of these cosolvents on the averaged sub-nanosecond dynamics in the
      pressure range from ambient up to 4000 bar. To evaluate the additional effect of
      self-crowding, two protein concentrations (80 and 160 mg mL-1) were used. We
      observed a distinct effect of TMAO on the internal hydrogen dynamics, namely a
      reduced mobility. Urea, on the other hand, revealed no marked effect and
      consequently, no counteracting effect in an urea-TMAO mixture was observed.
      Different from the less concentrated protein solution, no significant effect of
      pressure on the MSD was observed for 160 mg mL-1 lysozyme. The EINS experiments
      were complemented by Fourier-transform infrared (FTIR) spectroscopy measurements,
      which led to additional insights into the folding stability of lysozyme under the
      various environmental conditions. We observed a stabilization of the protein in
      the presence of the compatible osmolyte TMAO and a destabilization in the
      presence of urea against temperature and pressure for both protein
      concentrations. Additionally, we noticed a slight destabilizing effect upon self
      crowding at very high protein concentration (160 mg mL-1), which is attributable
      to transient destabilizing intermolecular interactions. Furthermore, a pressure
      temperature diagram could be obtained for lysozyme at these high protein
      concentrations that mimics densely packed intracellular conditions.

PMID- 28447689
TI  - Chemodynamics of metal ion complexation by charged nanoparticles: a dimensionless
      rationale for soft, core-shell and hard particle types.
AB  - Soft nanoparticulate complexants are defined by a spatial confinement of reactive
      sites and electric charges inside their 3D body. In turn, their reactivity with
      metal ions differs significantly from that of simple molecular ligands. A
      revisited form of the Eigen mechanism recently elucidated the processes leading
      to metal/soft particle pair formation. Depending on e.g. particle size and metal
      ion nature, chemodynamics of nanoparticulate metal complexes is controlled by
      metal conductive diffusion to/from the particles, by intraparticulate complex
      formation/dissociation kinetics, or by both. In this study, a formalism is
      elaborated to achieve a comprehensive and systematic identification of the rate
      limiting step governing the overall formation and dissociation of nanoparticulate
      metal complexes. The theory covers the different types of spherical particulate
      complexants, i.e. 3D soft/permeable and core-shell particles, and hard particles
      with reactive sites at the surface. The nature of the rate-limiting step is
      formulated by a dynamical criterion involving a power law function of the ratio
      between particle radius and an intraparticulate reaction layer thickness defined
      by the key electrostatic, diffusional and kinetic components of metal complex
      formation/dissociation. The analysis clarifies the intertwined contributions of
      particle properties (size, soft or hard type, charge, density or number of
      reactive sites) and aqueous metal ion dehydration kinetics in defining the
      chemodynamic behavior of nanoparticulate metal complexes. For that purpose, fully
      parameterized chemodynamic portraits involving the defining features of
      particulate ligand and metal ion as well as the physicochemical conditions in the
      local intraparticulate environment, are constructed and thoroughly discussed
      under conditions of practical interest.

PMID- 28447690
TI  - Bacterial magnetosomes - nature's powerful contribution to MPI tracer research.
AB  - The magnetic particle spectrum (MPS) of bacterial magnetosomes, isolated from
      Magnetospirillum gryphiswaldense, is measured and compared to that of the current
      "gold standard", Resovist(r). It is shown that the amplitudes of the
      magnetosomes' harmonics by far exceed that of Resovist(r); the amplitude of the
      third harmonic is higher by a factor of 7, and is the highest value obtained for
      iron oxide nanoparticles to date.

PMID- 28447691
TI  - Enhanced device lifetime of double-heterojunction nanorod light-emitting diodes.
AB  - Colloidal quantum dots (QDs) are emerging as solution-processable, high
      performance materials for light-emitting diodes (LEDs). Understanding the failure
      mechanism(s) is of both fundamental and practical importance, yet little is known
      of how QD-LEDs fail. Here, we have carried out accelerated device lifetime
      measurements on double heterojunction nanorod- (DHNR) and QD-LEDs. A common
      dependence of device lifetime on the initial driving voltage is observed over
      more than two orders of magnitude range in the initial luminance. This behavior
      is independent of whether the emitting materials are DHNRs or QDs prepared under
      different conditions. Reducing the hole injection barrier by doping HTL allows
      lower voltage operation, leading to longer device lifetimes. DHNRs with a band
      structure that further lowers the hole injection barrier require even lower
      driving voltages and therefore lead to longer device lifetimes than core/shell
      QDs. At 1000 cd m-2, the DHNR-LED exhibits no significant degradation even after
      more than 200 h of continuous operation. QD-LEDs, on the other hand, are
      completely degraded in less than ~100 h under the same initial luminance
      conditions. Hole accumulation/trapping leading to HTL degradation, which in turn
      deteriorates electroluminescence but not the photoluminescence, is suggested to
      be the main cause of degradation of both DHNR- and QD-LEDs.

PMID- 28447692
TI  - Pillar[5]arene-based [1]rotaxane: high-yield synthesis, characterization and
      application in Knoevenagel reaction.
AB  - We report a quantitative synthetic strategy of a [1]rotaxane from a
      representative pseudo[1]rotaxane. The structure of the [1]rotaxane was
      characterized by 1H NMR, 13C NMR, 2D NMR, mass spectroscopy, and melting point,
      and its optimized geometry in CHCl3 by theoretical calculation at the B3LYP/6
      31G(D) level using the PCM model matched well with 2D NOESY. This [1]rotaxane
      proves to be a good catalyst for the Knoevenagel reaction in CHCl3, which follows
      second order kinetics.

PMID- 28447693
TI  - Modulating the electronic structure of lanthanum manganite by ruthenium doping
      for enhanced photocatalytic water oxidation.
AB  - To the best of our knowledge this is the first report in which ruthenium doped
      polycrystalline lanthanum manganite, LaMn1-xRuxO3 (x = 0.0-0.4), having high
      efficacy for oxygen production from water without the use of any sacrificial
      reagent or co-catalyst and as an efficient photocatalyst for dye degradation is
      reported. Ruthenium doping alters the crystal structure of the parent LaMnO3
      (LMO) due to the induced chemical pressure of the larger Ru4+ ion, which
      facilitates a bond angle of 180 degrees  in the Mn3+-O-Mn4+ plane resulting in
      the easy extraction of a photo-generated charge carrier population leading to
      enhanced photocatalytic activity. Rietveld refinements reveal that the parent
      compound LMO crystallizes in the rhombohedral phase, while upon an increase in
      the doping concentration of ruthenium, the phase of the compounds changes from
      the rhombohedral to the cubic phase. The percentage contribution of each phase
      has been estimated using the sixth-order polynomial and pseudo-Voigt function.
      Typically, all the compositions, LaMn1-xRuxO3 (x = 0.0-0.4), were prepared by a
      conventional solid state route and studied for their photocatalytic activity. The
      synthesized compounds were investigated by powder X-ray diffraction (PXRD), UV
      visible diffuse reflectance spectroscopy (DRS), Fourier transform infrared
      spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), energy
      dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS)
      analysis. The structure-property correlation of the compound is presented based
      on Rietveld refinement combined with the experimental data. The as-prepared
      compounds show efficient photocatalytic oxygen gas production from water without
      the use of any co-catalyst or sacrificial reagents. Among the five compositions,
      LaMn0.7Ru0.3O3 shows the highest O2 production efficiency (4.73 mmol g-1 h-1)
      with an apparent quantum yield (AQY) of 7.43%. These ruthenium doped compositions
      also exhibit superior dye degradation properties, studied by taking the
      industrial dye methyl orange (MO) as the model compound.

PMID- 28447694
TI  - Formation of bimetallic dumbbell shaped particles with a hollow junction during
      galvanic replacement reaction.
AB  - The galvanic replacement reaction (GRR) has been shown to be an effective method
      to fine tune the structure of monometallic nanoparticles by controlling the
      precursor concentration and surface ligands. However, the structural evolution of
      nanoparticles is not well understood in multimetallic systems, where along with
      oxidation, dealloying and diffusion occur simultaneously. Here, we demonstrate
      that by controlling the rate of GRR in AuCu alloy nanorods, they can be
      transformed into either AuCu hollow rods or AuCu@Au core-shell spheroids.
      Interestingly, the transformation of rods into spheroids involved a critical
      intermediate state with a hollow junction and dumbbell shape. The formation of a
      hollow junction region was attributed to preferential diffusion of Cu atoms to
      the tips caused by the polycrystallinity and high curvature of the tips of the
      initial template. This structural transformation was also monitored in situ by
      single particle scattering spectroscopy. The coupling between the two ends of the
      dumbbell-shaped intermediate connected with a hollow metallic junction gives rise
      to additional plasmonic features compared with regular rods. Electrodynamic
      simulations showed that varying the dimensions of the hollow part by even one
      nanometer altered the plasmon resonance wavelength and lineshape drastically.
      This study shows that single particle plasmon resonance can be used as an
      exquisite tool to probe the internal structure of the nanoscale junctions.

PMID- 28447695
TI  - Phase transformation of TiO2 nanoparticles by femtosecond laser ablation in
      aqueous solutions and deposition on conductive substrates.
AB  - Titanium dioxide (TiO2) is a wide bandgap semiconductor that is chemically
      stable, non-toxic, and economical compared to other semiconductors and has been
      implemented in a wide range of applications such as photocatalysis,
      photovoltaics, and memristors. In this work we studied the femtosecond laser
      ablation of titanium dioxide powders (P25) dispersed either in water or deposited
      onto a fluoride-doped tin oxide (FTO) substrate. The process was used as a route
      to induce the phase-transformation of TiO2 nanoparticles which was governed by
      laser parameters such as ablation time and power. It was observed that upon
      increase of the ablation time of TiO2 dispersion in water a bandgap widening
      occurred, leading to the possibility of bandgap engineering of TiO2 using
      controlled laser parameter profiles.

PMID- 28447696
TI  - Photocatalytic photosystem I/PEDOT composite films prepared by vapor-phase
      polymerization.
AB  - Photosystem I (PSI) achieves photo-induced charge separation with outstanding
      internal quantum efficiency and has been used to improve the performance of
      various photoelectrochemical systems. Herein, we describe a fast and versatile
      technique to assemble composite films containing PSI and a chosen intrinsically
      conductive polymer (ICP). A mixture of PSI and a Friedel-Crafts catalyst (FeCl3)
      is drop cast atop a substrate of choice. Contact with ICP monomer vapor at low
      temperature stimulates polymer growth throughout PSI films in minutes. We assess
      the effects of PSI loading on the rapid vapor-phase growth of poly(3,4
      ethylenedioxythiophene) (PEDOT) within and above PSI multilayer films, and
      characterize the resulting film's thickness, electrochemical capacitance, and
      photocatalytic response. Composite films generate cathodic photocurrent when in
      contact with an aqueous redox electrolyte, confirming retention of the
      photocatalytic activity of the polymer-entrapped PSI multilayer assembly.

PMID- 28447697
TI  - Magnesium porphyrins with relevance to chlorophylls.
AB  - A review on the chemistry of magnesium porphyrins, which have significant
      interest owing to the relevance to chlorophyll molecules, is presented with
      emphasis on bicarbonate adducts of magnesium porphyrin and chlorophyll. The
      chemistry of 26 unique magnesium porphyrins is described as review articles on
      synthetic magnesium porphyrins are limited. Interest is given to the electron
      transfer reactions of magnesium porphyrins in artificial photosynthetic systems.
      The magnesium porphyrins are described considering coordination chemistry,
      structural aspects, electronic and electrochemical properties.

PMID- 28447698
TI  - Anisotropic metal nanoparticles for surface enhanced Raman scattering.
AB  - The optimization of the enhancement of Raman scattering by plasmonic effects is
      largely determined by the properties of the enhancing substrates. The main
      parameters behind this effect are related to the morphology of plasmonic
      nanoparticles and their relative distribution within the substrate. We focus this
      tutorial review on the effects of nanoparticle morphology, for the particular
      case of anisotropic metal nanoparticles. Anisotropy in silver and gold
      nanoparticles offers the possibility to tailor their plasmonic properties and
      intrinsic electromagnetic "hotspots". We describe the effect of varying particle
      size and shape on the SERS signal, focusing on the most common anisotropic
      morphologies used for SERS. Especial emphasis is made on existing comparative
      studies that shed light on the effect of nanoparticle anisotropy on their
      enhancement capabilities. We aim at providing a general perspective toward
      understanding the general key factors and highlighting the difficulty in
      quantitatively determining SERS performance.

PMID- 28447699
TI  - Determination of paramagnetic concentrations inside a diamagnetic matrix using
      solid-state NMR.
AB  - The determination of very low doping levels in solid materials is an important
      issue for many applications. When considering paramagnetic dopants, the NMR
      relaxation technique appears to be much more accurate than classical techniques
      such as Vegard's law resulting from X-ray diffraction (XRD) measurements or
      chemical analysis that cannot provide information on appropriate dopant spatial
      distributions. In a recent report, the linear variation of 1/T1, i.e. the nuclear
      relaxation rate, as a function of Nd3+ content has been used to determine doping
      levels with a good dispersion homogeneity in the monazite LaPO4 matrix down to
      0.1 mol%. We here extend this study to more complex compounds doped with Nd3+,
      such as YPO4, the solid solution Y0.8Sc0.2PO4, Ba5(PO4)3Cl and a phosphate glass.
      For all considered compounds except Ba5(PO4)3Cl:Nd, 1/T1 is found to be linearly
      proportional to the nominal Nd concentration, confirming the ability of the
      method to investigate the dopant concentration and spatial homogeneity. The
      results obtained for different compounds open up the discussion on the
      parameters, such as the orbital overlap and the average P-P distances,
      influencing the nuclear relaxation rate.

PMID- 28447700
TI  - Evolution inspired engineering of antibiotic biosynthesis enzymes.
AB  - Streptomyces soil bacteria are competent chemists that are able to produce
      thousands of chemically complex natural products. Key to the development of this
      rich source of metabolites appears to be an evolutionary pressure that promotes
      chemical diversity; new biosynthetic pathways are continuously being formed in
      these bacteria, which may result in the appearance of a novel bioactive compound
      that provides significant competitive advantage to the producing organism. In
      recent years, our work has focused on understanding how minor changes in the
      biosynthetic enzymes has led to drastically altered catalytic properties. We have
      generated chimeric proteins from functionally distinct homologous enzymes
      involved in the tailoring steps of related anthracycline and angucycline
      pathways, with the aim of creating novel catalysts. The work provides an
      opportunity for further protein engineering efforts for production of improved
      bioactive natural products.

PMID- 28447701
TI  - Structural and morphological transitions in extension-induced crystallization of
      poly(1-butene) melt.
AB  - Structural and morphological transitions of flow-induced crystallization (FIC) in
      poly(1-butene) (PB-1) melt have been studied by combining extensional rheology
      and in situ synchrotron radiation ultrafast wide- and small-angle X-ray
      scattering (WAXD/SAXS) measurements. Unexpectedly, metastable Form III is
      crystallized directly from the PB-1 melt by high-speed extension, which has a
      short lifetime of several tens of milliseconds and manifests the thermodynamic
      and kinetic competition among Form III, Form II and melt under flow. Relative
      crystallinity evolution of Form II after extension reveals a crystal melting
      dominated process within the observation time of 120 s even under high
      supercooling. This is opposite to the common case of FIC but supports the idea
      that flow alters the obtained crystal size and its thermodynamic stability.
      Additionally, a morphological transition from a flow-induced network to shish is
      observed by SAXS with increasing extension temperature from below to above the
      melting point of Form II. With above observations, we construct nonequilibrium
      structural and morphological diagrams of FIC in strain rate-temperature space,
      which may guide the industrial processing of the PB-1 material.

PMID- 28447702
TI  - Structures in the meniscus of smectic membranes: the role of dislocations?
AB  - We report an experimental investigation of the structure of periodic patterns
      observed in the meniscus of free-standing smectic films. Combination of
      polarizing optical microscopy and phase shifting interferometry enabled us to
      obtain new information on the structure of the meniscus, and in particular, on
      the topography of the smectic-air interface. We investigate the profile of the
      undulations in the striped structure in the thin part of the meniscus, change of
      the stripe period with the meniscus thickness and subsequent transition into a
      two-dimensional structure. It is shown that the two-dimensional structure has an
      unusual complex profile of "egg-box" type. The striped texture occurs upon
      cooling from the nontilted smectic-A to the smectic-C* phase, whereas the two
      dimensional pattern is present in both phases. We discuss the possible origin of
      the modulated structures, the role of the dislocations in the meniscus, the
      elasticity of smectic layers, and the mechanical stress induced by dislocations.

PMID- 28447703
TI  - Conserved effects and altered trafficking of Cetuximab antibodies conjugated to
      gold nanoparticles with precise control of their number and orientation.
AB  - Gold nanoparticles (17 nm) have been functionalized with the antiangiogenic
      monoclonal antibody drug Cetuximab at a well-defined orientation and coverage
      density of antibodies. Functionalization has been carried out through site
      directed chemistry via the selective oxidation of the carbohydrate moiety of
      antibodies linked to a thiolated hydrazide. A431 tumor cells have been exposed to
      these conjugates for in vitro evaluation of their effects. In addition to
      epithelial growth factor receptor blocking, trafficking and signaling alterations
      were also observed. Thus, the blocking effects of Cetuximab were increased and
      sustained for a longer time when associated with the nanoparticles. Enhancing
      antibody therapy effects by decreasing the needed dose and prolonging its effect
      by avoiding receptor recycling may serve to obtain increased therapeutic benefits
      for immunotherapy.

PMID- 28447704
TI  - Influence of dopants on the impermeability of graphene.
AB  - Graphene has attracted much attention as an impermeable membrane and a protective
      coating against oxidation. While many theoretical studies have shown that defect
      free graphene is impermeable, in reality graphene inevitably has defects in the
      form of grain boundaries and vacancies. Here, we study the effects of N-dopants
      on the impermeability of few-layered graphene (FLG) grown on copper using
      chemical vapor deposition. The grain boundaries in FLG have minimal impact on
      their permeability to oxygen as they do not provide a continuous channel for gas
      transport due to high tortuosity. However, we experimentally show that the N
      dopants in FLG display multiple configurations that create structural
      imperfections to selectively allow gas molecules to permeate. We used a
      comprehensive array of tools including Raman spectroscopy, X-ray photoelectron
      spectroscopy, optically stimulated electron emission measurements, and density
      functional theory of N-doped graphene on copper to elucidate the effects of
      dopant configuration on the impermeability of graphene. Our results clearly show
      that oxygen can permeate through graphene with non-graphitic nitrogen dopants
      that create pores in graphene and oxidize the underlying Cu substrate while
      graphitic nitrogen dopants do not show any changes compared to the pristine form.
      Furthermore, we observed that the work function of graphene can be tuned
      effectively by changing the dopant configuration.

PMID- 28447706
TI  - Insights into the surface chemistry and electronic properties of sp2 and sp3
      hybridized nanocarbon materials for catalysis.
AB  - Ultra-dispersed nanodiamond and its derivatives (UNDDs), including bucky
      nanodiamond and onion-like carbon, offer superior catalytic behavior relative to
      other nanocarbons. However, a systematic study of their unique properties has
      been rarely achieved. Their surface chemistry and electronic properties are
      therefore studied to reveal the essential differences of UNDDs compared to other
      nanocarbons for catalysis.

PMID- 28447707
TI  - Thickness-dependent Schottky barrier height of MoS2 field-effect transistors.
AB  - 2D semiconductors, including transition metal dichalcogenides (TMDs), have been
      widely studied recently. However, the device performance is deteriorated due to
      the significant contact resistance. The contact resistance of MoS2-metal contacts
      decreases with the thickness of MoS2. We obtained a Schottky barrier height as
      low as about 70 meV when MoS2 is trilayer-thick. It is important to find the
      optimal choice of contact metal and layer thickness of MoS2.

PMID- 28447708
TI  - Protein collapse is encoded in the folded state architecture.
AB  - Folded states of single domain globular proteins are compact with high packing
      density. The radius of gyration, Rg, of both the folded and unfolded states
      increase as Nnu where N is the number of amino acids in the protein. The values
      of the Flory exponent nu are, respectively, ~1/3 and ~0.6 in the folded and
      unfolded states, coinciding with those for homopolymers. However, the extent of
      compaction of the unfolded state of a protein under low denaturant concentration
      (collapsibility), conditions favoring the formation of the folded state, is
      unknown. We develop a theory that uses the contact map of proteins as input to
      quantitatively assess collapsibility of proteins. Although collapsibility is
      universal, the propensity to be compact depends on the protein architecture.
      Application of the theory to over two thousand proteins shows that collapsibility
      depends not only on N but also on the contact map reflecting the native
      structure. A major prediction of the theory is that beta-sheet proteins are far
      more collapsible than structures dominated by alpha-helices. The theory and the
      accompanying simulations, validating the theoretical predictions, provide
      insights into the differing conclusions reached using different experimental
      probes assessing the extent of compaction of proteins. By calculating the
      criterion for collapsibility as a function of protein length we provide
      quantitative insights into the reasons why single domain proteins are small and
      the physical reasons for the origin of multi-domain proteins. Collapsibility of
      non-coding RNA molecules is similar beta-sheet proteins structures adding support
      to "Compactness Selection Hypothesis".

PMID- 28447710
TI  - Khorana score and histotype predicts incidence of early venous thromboembolism in
      non-Hodgkin lymphomas. A pooled-data analysis of 12 clinical trials of Fondazione
      Italiana Linfomi (FIL).
AB  - Current data suggests that the risk of venous thromboembolism (VTE) in patients
      with non-Hodgkin lymphoma (NHL) is comparable to that observed in patients with
      solid tumours, although more robust confirmatory analyses are required. With that
      in mind, we investigated the occurrence of VTE in a pooled analysis of 12
      "Fondazione Italiana Linfomi" (FIL) prospective clinical studies. Specifically,
      we wished to assess the cumulative incidence of VTE in NHL patients, evaluate the
      predictive value of the Khorana Score (KS), and identify other potential risk
      factors for VTEs. Data for VTE occurrence were retrieved from study databases and
      pharmacovigilance reports. Our analysis includes 1717 patients from 12
      prospective phase II and III trials, including newly diagnosed NHL. We observed
      53 VTEs (any grade) in 46 patients, with 20 severe VTEs in 17 patients. The
      cumulative incidences for "all-grade" or grade >=3 VTEs were 2.9 % (95 % CI: 2.1
      3.8) and 1.1 % (95 % CI: 0.6-1.6), respectively. KS categories were positively
      associated with the risk of VTE of any grade, and with severe events (i. e. grade
      >=3; Gray's test p-values = 0.048 and 0.012, respectively). Among NHL patients,
      those with diffuse large B-cell lymphoma (DLBCL) showed a greater risk of (any
      grade) VTE (HR: 3.42, 95 % CI: 1.32-8.84, p-value = 0.011). Our study indicates
      that 1) VTE is a relevant complication for NHL patients, 2) KS is predictive of
      VTE events and 3) DLBCL histotype is an independent risk factor for VTE
      incidence, for which preventative interventions could be considered.

PMID- 28447709
TI  - [Atypical Cushing's syndrome in a dog. A case report].
AB  - In a 12-year-old male Labrador Retriever, presented due to other disease
      symptoms, clinical signs of hyperadrenocorticism (polyuria, polydipsia, abdominal
      distention, muscle atrophy) were an incidental finding. Abnormal laboratory
      results and sonographic findings of the adrenal glands, but negative low-dose
      dexamethasone suppression tests with low basal cortisol concentrations, a
      negative andrenocorticotropic hormone (ACTH)-stimulation test and exclusion of
      iatrogenic hyperadrenocorticism, suggested an atypical hyperadrenocorticism
      (AHAC). Results of further examinations, particularly stimulation of progesterone
      production by ACTH (0 h value: 0.21 ng/ml; 1 h value: 4.9 ng/ml) and good
      response to therapy with trilostane, supported this diagnosis. However, it has to
      be critically considered, whether and to what extent additionally present
      diseases (arthroses, testicular tumour) played a role regarding the symptoms and
      laboratory results in this dog. This case illustrates the difficulties with the
      diagnosis of AHAC.

PMID- 28447711
TI  - Alleviative effect of grape seed proanthocyanidin extract on small artery
      vascular remodeling in spontaneous hypertensive rats via inhibition of collagen
      hyperplasia.
AB  - Vascular remodeling is a primary contributor to the initiation and development of
      hypertension, which has a pathological association with subsequent multi-organ
      damage. Grape seed proanthocyanidin extracts (GSPE) exhibit protective
      cardiovascular effects, resulting from their anti-oxidant and anti-inflammatory
      properties. However, the function and mechanism underlying the effect of GSPE on
      small artery remodeling remain to be elucidated. The present study investigated
      the effect of GSPE on vascular remodeling in the mesenteric small arteries of
      spontaneous hypertensive rats (SHR). Parameters associated with hypertension,
      including systolic blood pressure, oxidative stress, morphological and
      ultrastructural alteration of vessels, deposition of collagen and transforming
      growth factor (TGF)-beta1, were analyzed. The results revealed that GSPE
      alleviated hypertension-induced hypertrophic vascular remodeling in the small
      arteries of SHR, which was independent of blood pressure. GSPE decreased
      oxidative stress associated with hypertension in SHR and suppressed the increased
      expression of TGF-beta1, which blocked the translocation and differentiation of
      adventitia fibroblasts and eventually inhibited collagen hyperplasia in the blood
      vessel. The inhibitory effect of GSPE on small artery remodeling was achieved via
      its suppressive effect on oxidant production and the subsequent intercellular and
      intracellular cascades. The findings of the present study supported the potential
      therapeutic value of GSPE for the treatment of hypertension.

PMID- 28447712
TI  - Wiryeongtang regulates hypertonicity-induced expression of aquaporin-2 water
      channels in mIMCD-3 cells.
AB  - The kidneys have a key role in the homeostasis of water excretion and
      reabsorption. Water channels, particularly aquaporin-2 (AQP2), are important
      proteins in water homeostasis in the body through the short-term and long-term
      regulation of water permeability. Wiryeongtang (WRT) is a well-known traditional
      oriental medicine, which is used for the treatment of chronic edema and
      dysuresia. The aim of the present study was to evaluate the inhibitory effect of
      WRT on the hypertonicity-induced expression of AQP2 in the inner medullary
      collecting duct cell line (IMCD-3). Western blotting, reverse transcription
      polymerase chain reaction and immunofluorescence analysis were performed to
      determine the effect of WRT under hypertonic stress. WRT attenuated the 175 mM
      NaCl hypertonic stress-induced increases in protein and mRNA levels of AQP2 and
      apical membrane insertion in a concentration-dependent manner. However, no
      differences were observed in the levels of AQP1, AQP3 or AQP4 between the
      hypertonic stress and WRT groups. WRT attenuated the hypertonicity-induced
      phosphorylation of glucocorticoid-inducible protein kinase 1. In addition, the
      mRNA expression of tonicity-responsive enhancer binding protein was attenuated by
      WRT under hypertonic stress. Pretreatment with WRT also decreased the hypertonic
      stress-induced expression of AQP2, as with KT5720, a protein kinase A inhibitor.
      These results provided evidence of the beneficial effect of the traditional
      formula WRT in regulating water balance in hypertonic stress of the renal
      collecting ducts.

PMID- 28447713
TI  - Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive
      to cell density.
AB  - Retinoblastoma is the most common ocular tumor in children, and it causes
      extensive damage. Current treatment options for retinoblastoma include surgery,
      chemotherapy, radiotherapy and cryotherapy. However, the majority of chemotherapy
      medicines cause complications and side effects that lead to severe impairment of
      patient health. Previous studies have reported that tetramethylpyrazine (TMP),
      which is an extract of the Chinese herbal medicine Chuanxiong, reduces the risk
      of multidrug resistance in chemotherapy and inhibits the proliferation and
      metastasis of various types of cancer cells. However, the underlying molecular
      mechanism of TMP in retinoblastoma remains unclear. The current study
      demonstrated that C-X-C chemokine receptor type 4 (CXCR4) was expressed in WERI
      Rb1 cells and in retinoblastoma. Using reverse transcription-quantitative
      polymerase chain reaction and western blotting techniques, the current study
      demonstrated that TMP significantly downregulated the expression of CXCR4 in WERI
      Rb1 cells cultured at high density, whereas it had a minor effect in low-density
      WERI-Rb1 cells; additionally, this effect occurred in a time-dependent manner.
      TMP inhibited the proliferation of WERI-Rb1 cells as effectively as a CXCR4
      antagonist, AMD3100, consistent with a role of CXCR4 in cancer development.
      Notably, TMP did not affect the cell cycle of cells cultured at low density
      (1x105 cells/ml), whereas it induced G1-phase arrest in high-density cells
      (7.5x105 cells/ml; P<0.05). In addition, the expression of CXCR4 in primary rat
      retinal neurocytes was significantly downregulated by TMP treatment, and this
      treatment protected primary rat retinal neurocytes from H2O2-induced damage.
      Thus, the results of this study indicate that TMP is a potential candidate for
      use in treatment of retinoblastoma, and also provides novel insights into the
      mechanisms of the anti-cancer and neuroprotective effects of this extract.

PMID- 28447714
TI  - Resveratrol protects against oxidized low-density lipoprotein-induced human
      umbilical vein endothelial cell apoptosis via inhibition of mitochondrial-derived
      oxidative stress.
AB  - Resveratrol, a natural phytochemical found in grapes and red wine, has been found
      to possess protective effects against endothelial cell apoptosis and oxidative
      damage. Oxidized-low density lipoprotein (ox-LDL) can induce apoptosis of
      endothelial cells, which is an important initial event in several cardiovascular
      diseases. However, the effect of resveratrol on ox-LDL-induced apoptosis and
      oxidative damage, and the possible associated mechanisms remain to be elucidated.
      In the present study, following exposure to ox-LDL, human umbilical vein
      endothelial cells (HUVECs) were treated with or without resveratrol. Cell
      viability was examined using Cell Counting Kit-8 and 5-bromo-2'-deoxyuridine
      uptake assays, respectively. Cell apoptosis was determined by flow cytometry.
      Apoptosis-associated markers were detected using western blot analysis. Oxidative
      stress was analyzed using molecular and biochemical approaches. Resveratrol
      restored ox-LDL-induced HUVEC injury and apoptosis in a dose-dependent manner. In
      addition, compared with the control group, ox-LDL treatment decreased the B cell
      lymphoma-2 (Bcl-2)/Bcl-2-associated X protein ratio, mitochondrial membrane
      potential and activation of superoxide dismutase, and enhanced the release of
      mitochondrial cytochrome c into the cytoplasm, the activation of caspase and
      lipid peroxidation. All these alterations were significantly inhibited following
      treatment with resveratrol. The results demonstrated that resveratrol prevented
      HUVEC apoptosis through inhibiting mitochondria-derived oxidative damage. These
      findings may provide a novel mechanism by which resveratrol prevents against
      endothelial cell apoptosis.

PMID- 28447715
TI  - Correlation of the expression of YY1 and Fas cell surface death receptor with
      apoptosis of peripheral blood mononuclear cells, and the development of multiple
      organ dysfunction in children with sepsis.
AB  - Multiple organ dysfunction (MOD) is a lethal complication in children with
      sepsis. Apoptosis of several cell types is involved in this process, and it is
      associated with increased Fas cell surface death receptor (Fas) expression. As
      YY1 transcription factor (YY1) negatively regulates the expression of Fas in
      cancer models, and is associated with the clinical outcome, it may be important
      in MOD. The present study aimed to determine the association between the
      expression of Fas, YY1 and apoptosis in children with sepsis, and its association
      with MOD, these factors were analyzed in 30 pediatric patients that had been
      diagnosed with sepsis. Peripheral blood mononuclear cells were purified from
      patients, and YY1 and Fas protein expression was assessed by immunocytochemistry.
      Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end
      labeling. Sepsis was monitored using clinical parameters, pediatric logistic
      organ dysfunction (PELOD) score and the pediatric mortality index. The results
      demonstrated that Fas expression was directly correlated with apoptosis levels
      and the expression of YY1 was inversely correlated with apoptosis levels.
      Patients with high levels of apoptosis exhibited increased disease severity and
      poor clinical outcome. Notably, the findings of the present study demonstrated
      that there were higher survival rates in patients with high YY1 expression,
      compared with those with low YY1 expression. Additionally, patients with MOD
      exhibited lower proportions of apoptotic cells compared with sepsis patients
      without MOD. Furthermore, the PELOD score was positively correlated with Fas and
      inversely correlated with YY1 expression. Finally, high apoptosis and low YY1
      expression were prognostic factors associated with poor survival rates. These
      data suggested that YY1 may be important for apoptosis induction via the
      regulation of Fas during sepsis. Therefore, Fas may be a potential therapeutic
      target to prevent MOD through regulation of YY1 expression. Furthermore, YY1 and
      Fas expression in PBMCs may be used to as prognostic markers.

PMID- 28447716
TI  - PAR1-mediated c-Jun activation promotes heat stress-induced early stage apoptosis
      of human umbilical vein endothelial cells.
AB  - Our previous study indicated that when human umbilical vein endothelial cells
      (HUVECs), which are involved in endothelial barrier function, are heat stressed,
      levels of protease-activated receptor 1 (PAR1) are increased significantly. In
      the present study, it was demonstrated that PAR1 serves a vital role in heat
      stress-induced HUVEC apoptosis. When the PAR1 inhibitor, SCH79797 (SCH), or a
      small interfering RNA (siRNA) targeting PAR1 were used to inhibit PAR1 signaling,
      a marked decrease in cell apoptosis, caspase-3 activity and the expression of the
      pro-apoptotic protein B-cell lymphoma 2 (Bcl-2) associated X (Bax), as well as
      increased expression of the anti-apoptotic Bcl-2 family member, myeloid cell
      leukemia 1 (Mcl-1), were observed. In addition, heat stress-induced apoptosis,
      caspase-3 activity and the expression of Bax were significantly increased
      following administration of the PAR1 agonist, TFLLR-NH2 or adenovirus
      overexpression of PAR1. This was accompanied by decreased protein expression
      levels of Mcl-1. Furthermore, it was identified that the DNA binding activity of
      the nuclear factor (NF)-kappaB p65 subunit increased and c-Jun activation was
      reduced as a result of inhibition of PAR1 signaling by SCH or siRNA-mediated PAR1
      knockdown in heat stress-induced HUVECs. Additionally, our previous study
      reported that NF-kappaB p65 activation may have an anti-apoptosis effect on heat
      stressed HUVECs, whereas in the present study c-Jun activation had a pro
      apoptosis effect on heat stressed HUVECs. Taken together, these results indicated
      that PAR1 signaling-mediated c-Jun activation promotes early apoptosis of HUVEC
      cells induced by heat stress.

PMID- 28447717
TI  - Knockdown of ZFPL1 results in increased autophagy and autophagy-related cell
      death in NCI-N87 and BGC-823 human gastric carcinoma cell lines.
AB  - Macroautophagy, which will hereafter be referred to as autophagy, is an
      evolutionarily conserved process, during which cells recycle and remove damaged
      organelles and proteins in response to cellular stress. However, the mechanisms
      underlying the regulation of autophagy remain to be fully elucidated. The present
      study demonstrated that knockdown of zinc finger protein like 1 (ZFPL1) induces
      autophagy and increases autophagic cell death in NCI-N87 and BGC-823 human
      gastric carcinoma cell lines. To examine the role of ZFPL1 in gastric carcinoma
      cells, ZFPL1 expression was downregulated by lentiviral infection. Zinc finger
      domain-FLAG was used to compete with ZFPL1 for golgin A2/GM130 binding. Autophagy
      was analyzed by red fluorescent protein-microtubule-associated protein 1A/1B
      light chain 3 (LC3) puncta, LC3I to LC3II conversion, and p62 expression. The
      results demonstrated that knockdown of ZFPL1 was able to significantly increase
      cell death rate. However, ZFPL1 knockdown exerted almost no effect on the
      expression of apoptosis-associated markers, including B cell lymphoma 2 (Bcl-2),
      Bcl-x, Bcl-2-associated X protein, BH3 interacting domain death agonist, p53, and
      the classical caspase family members, caspase-3, caspase-8 and caspase-9. An
      endogenous ZFPL1-GM130 association was identified in NCI-N87 cells and BGC-823
      cells by co-immunoprecipitation. Furthermore, cell death was restricted following
      treatment of ZFPL1 knockdown cells with an autophagy inhibitor. Therefore,
      knockdown of ZFPL1 expression may induce cell death via autophagy, rather than
      apoptosis. These results suggest that ZFPL1 may serve an important role in
      regulating autophagy in NCI-N87 and BGC-823 cells.

PMID- 28447718
TI  - Role of histone deacetylase expression levels and activity in the inflammatory
      responses of patients with chronic hepatitis B.
AB  - Histone acetylation has been demonstrated to serve a pivotal role in numerous
      inflammatory diseases. The present study examined histone acetylation in patients
      with chronic hepatitis B (CHB) and CHB with liver failure by detecting histone
      deacetylase (HDAC) activity. Mice with acute liver failure (ALF) were treated
      with the HDAC inhibitor entinostat (MS275) and alterations in HDAC activity and
      pro-inflammatory cytokine expression levels were detected. The effect of HDAC1
      silencing on LPS-treated RAW264.7 murine macrophages was examined using specific
      small interfering RNA sequences, and the acetylation level of the non-histone
      nuclear factor-kappaB (NF-kappaB) p65 subunit was additionally examined. The
      results demonstrated that serum levels of alanine aminotransferase, aspartate
      aminotransferase and total bilirubin, and the expression levels of pro
      inflammatory cytokines, were significantly increased in patients with CHB.
      Aberrant histone acetylation and HDAC activity were identified in patients with
      CHB, with their levels associating with disease severity. MS275 treatment may
      decrease HDAC activity and inhibit the production of cytokines; however,
      acetylation levels of H3 and H4 were enhanced. Acetylation levels of NF-kappaB
      p65 were decreased in lipopolysaccharide-treated cells and ALF mice, and were
      promoted by MS275 treatment and HDAC1 silencing. In conclusion, alterations in
      HDAC activity and expression levels demonstrated a greater effect on inflammation
      compared with histone acetylation; therefore, the underlying mechanisms may be
      associated with the acetylation of non-histones. These results provide a
      potential novel therapeutic strategy for the treatment of CHB.

PMID- 28447719
TI  - Hepatocyte growth factor inhibits tubular epithelial-myofibroblast
      transdifferentiation by suppression of angiotensin II via the JAK2/STAT3
      signaling pathway.
AB  - Tubular epithelial-myofibroblast transdifferentiation (TEMT) is important in the
      development of chronic renal failure. The present study investigated whether
      hepatocyte growth factor (HGF) inhibits TEMT, and whether this function may be
      associated with the inhibition of angiotensin II (AngII) and the Janus kinase
      2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling
      pathway. Human HK-2 kidney proximal tubular cells were divided into 4 groups and
      treated with AngII (1x10-6 M), HGF (8x10-3 M), AngII plus HGF or control
      conditions, followed by an assessment of apoptosis induction and the expression
      levels of alpha-smooth muscle actin (alpha-SMA), which is a marker of TEMT. as
      well as the activation level of JAK2, phosphorylated (p)-JAK2, STAT3 and p-STAT3
      signaling pathways. In HK-2 cells, alpha-SMA mRNA and protein expression levels
      increased following treatment with AngII, however, decreased expression was
      observed following exposure to HGF. HGF counteracted the AngII-induced increase
      in the expression of alpha-SMA in HK-2 cells. Similar expression profiles were
      observed for the phosphorylated forms of JAK2 and STAT3, indicating the possible
      involvement of this signaling pathway. The results demonstrated that treatment of
      cells with AngII was associated with the induction of apoptosis when compared
      with the control. By contrast, treatment with HGF attenuated AngII-induced
      apoptosis. The results suggested that HGF may inhibit TEMT by inhibiting AngII
      through the JAK2/STAT3 signaling pathway in HK-2 cells and HGF may prevent
      apoptosis induced by AngII. The present study provides a basis for understanding
      the mechanisms involved in the inhibition of TEMT by HGF, which requires further
      investigation.

PMID- 28447721
TI  - Clinical significance of inflammatory cytokine and chemokine expression in hand,
      foot and mouth disease.
AB  - The present study examined the relationship between cytokine and chemokine
      expression and the clinical presentation of hand, foot and mouth disease (HFMD),
      which is currently unclear. The present study involved 28 patients with mild
      HFMD, 44 patients with severe HFMD and 26 healthy children. Venous blood was
      tested for cytokine [interleukin (IL)-4, IL-12, IL-18, tumor necrosis factor
      alpha (TNF-alpha), interferon-gamma (IFN-gamma)] and chemokine expression [IL-8,
      regulated on activation, normal T cell expressed and secreted (RANTES), monocyte
      chemoattractant protein-1 (MCP-1) and IFN-gamma-inducible protein-10 (IP-10)].
      Stool samples from the patients were tested for enterovirus 71 (EV71) RNA using
      reverse transcription-polymerase chain reaction. The results indicated that all
      cytokine/chemokine levels were increased in patients with severe HFMD compared
      with in patients with mild HFMD or control subjects. In addition, RANTES, MCP-1,
      IL-4, IL-12 and IL-18 levels were higher in mild HFMD patients than in the
      controls. In patients with severe HFMD, all expression levels (with the exception
      of IL-8 and IL-4) were increased in patients with encephalitis plus pulmonary
      edema compared with those with encephalitis alone. Furthermore, all levels (with
      the exception of IL-8) were increased in EV71-positive patients compared with
      EV71-negative patients. In mild HFMD, all levels (with the exception of IL-8 and
      IL-4) were increased in EV71-positive patients compared with EV71-negative
      patients. However, in severe HFMD, only RANTES, IP-10 and IFN-gamma levels were
      increased in EV71-positive patients compared with EV71-negative patients. In the
      EV71-negative group, all levels were increased in severe HFMD compared with mild
      HFMD. In the EV71-positive group, all levels (with the exception of IL-8) were
      increased in severe HFMD compared with mild HFMD. These results indicated that
      cytokines and chemokines participate in HFMD pathogenesis, and may be useful to
      monitor disease progression and predict prognosis.

PMID- 28447720
TI  - p75 neurotrophin receptor: A potential surface marker of tongue squamous cell
      carcinoma stem cells.
AB  - The present study detected p75 neurotrophin receptor (p75NTR) expression in
      tongue squamous cell carcinoma (TSCC) cell lines, in order to define the
      biological properties of p75NTR+ cells and to confirm the use of p75NTR+ as a
      surface marker for TSCC stem cells. p75NTR+ cells were separated from Tca-8113
      and CAL-27 TSCC cells by fluorescence-activated cell sorting. Colony formation,
      MTT and scratch assays, and a tumorigenicity analysis were performed to measure
      self-renewal and proliferation, multidirectional differentiation, and
      tumorigenicity of p75NTR+ cells. p75NTR+ cells comprised 3.1 and 1.9% of Tca-8113
      and CAL-27 cells (mean of three experiments), respectively, and were more able to
      form colonies compared with non-sorted cells (P<0.01). In addition, the
      proportion of p75NTR+ cells generated from monoclonal p75NTR+ cells decreased to
      14.5 (Tca-8113) and 5.8% (CAL-27) of cells within 2 weeks, thus suggesting that
      p75NTR+ cells are able to generate p75NTR+ and p75NTR- cells. Furthermore,
      p75NTR+ cells exhibited increased proliferation, as evidenced by MTT assay
      (P<0.01) and had greater metastatic ability according to the scratch assay
      (P<0.01), compared with non-sorted cells. p75NTR+ cells also exhibited a greater
      tumorigenic capacity compared with non-sorted cells. In conclusion, p75NTR+ cells
      isolated from TSCC cell lines possess the characteristics of cancer stem cells;
      therefore, p75NTR may be considered a useful surface marker for the
      identification of TSCC stem cells.

PMID- 28447722
TI  - Novel compound heterozygous PLEC mutations lead to early-onset limb-girdle
      muscular dystrophy 2Q.
AB  - Limb-girdle muscular dystrophy 2Q (LGMD2Q) is a specific mutation in the plectin
      (PLEC1) gene at chromosome 8q24.3. In the present study, targeted sequencing
      using a muscle disease gene panel was performed in a patient with muscular
      dystrophy. The family members were confirmed by Sanger sequencing. The PolyPhen
      2, SIFT and MutationTaster tools were used to predicted the possible effect of
      the mutations. Immunocytochemistry was used to visualize and localize the plectin
      protein within the gastrocnemius. Novel compound heterozygous mutations c.5995C>T
      (p.Arg1999Trp) and c.9940T>A (p.Phe3314 Ile) in the PLEC gene were identified to
      be the genetic cause of LGMD2Q in this family. These variants were absent in 200
      normal controls. Furthermore, defects in the plectin protein within the
      gastrocnemius were determined using immunocytochemistry. To the best of our
      knowledge, the present study provides the second report on plectin-associated
      LGMD2Q without other symptoms, although the genotype identified was novel. The
      missense mutations in the proband were considered to be an explanation for the
      symptom. These findings extend current knowledge of the mutation spectrum of the
      PLEC gene associated with LGMD2Q.

PMID- 28447723
TI  - Upregulation of RASAL2 promotes proliferation and metastasis, and is targeted by
      miR-203 in hepatocellular carcinoma.
AB  - RAS protein activator like 2 (RASAL2) has been reported to be dysregulated in
      various types of cancer. It has previously been demonstrated that RASAL2 is
      hypomethylated in hepatocellular carcinoma (HCC). However, the expression pattern
      of RASAL2 and its potential role in HCC remain to be elucidated. The present
      study demonstrated that the expression of RASAL2 was upregulated in HCC tissues,
      compared with in normal liver tissues, by using immunohistochemistry. In
      addition, Cell Counting Kit-8 assay and invasion assay revealed that knockdown of
      RASAL2 inhibited the growth and invasion of HCC cells. Western blotting results
      indicated that the inhibition of RASAL2 reduced the levels of phosphorylated-AKT.
      Notably, RASAL2 was observed to be a direct target of miR-203 in HCC in
      luciferase activity assays. Furthermore, overexpression of miR-203 exhibited a
      similar effect to RASAL2 knockdown in HCC cells. These results indicated that
      RASAL2 serves a tumor oncogenic role in HCC and may be considered a potential
      target in HCC.

PMID- 28447724
TI  - Effects of gap junction intercellular communication on the docetaxel-induced
      cytotoxicity in rat hepatocytes.
AB  - The effect of gap junction intercellular communication (GJIC) on docetaxel
      induced hepatotoxicity and its underlying mechanisms are largely unknown. The
      present study involved investigating the effect of downregulating GJs derived
      from connexin (Cx) 32 in BRL-3A cells by three different mechanisms: Using a low
      density culture; suppression of Cx32 using small interfering RNA; and use of the
      chemical inhibitor 2-aminoethoxydiphenyl borate (2-APB), all of which led to
      attenuated docetaxel hepatotoxicity. In order to investigate the relevant
      mechanisms involved, apoptosis and caspase activities of BRL-3A cells were
      determined. The increase of apoptosis and the activation of caspase-3 and caspase
      9, but not caspase-8, were detected following cell exposure with docetaxel,
      demonstrating that the mitochondrial-mediated apoptosis pathway is largely
      responsible for docetaxel hepatotoxicity. However, reduced apoptosis and caspase
      3, and -9 activities were observed following docetaxel application when BRL-3A
      GJIC was deficient from the knockdown of Cx32 expression or pretreatment with 2
      APB. These observations illustrate that GJs are important in docetaxel-induced
      hepatotoxicity. Furthermore, inhibition of GJIC could prevent amplification of
      toxicity to docetaxel. Due to GJIC blockage, this hepatoprotection was
      associated, in part, with decreasing apoptosis of BRL-3A cells through the
      mitochondrial pathway. The present study provides evidence for potential
      therapeutic targets for the treatment of docetaxel-induced liver injury.

PMID- 28447725
TI  - Expression levels of resistant genes affect cervical cancer prognosis.
AB  - Tumor cells may develop multidrug resistance (MDR) to various chemotherapy
      regimens. Such resistance reduces the sensitivity of cells to chemotherapy drugs,
      leading to the failure of cervical cancer (CC) treatment and disease progression.
      The present study aimed to investigate the role of MDR1, lung resistance protein
      (LRP) and placental glutathione S-transferase pi 1 (GSTP1) in CC and MDR, and the
      prognostic value of these genes. The mRNA expression levels of these resistance
      associated genes were determined in 47 CC and 20 healthy cervical tissue samples.
      Subsequently, the data was analyzed alongside clinicopathological parameters. The
      mRNA expression levels of MDR1, LRP and GSTP1 in CC were 0.57+/-0.32, 0.58+/-0.29
      and 0.44+/-0.24, respectively, whereas those in healthy cervical tissues were
      0.19+/-0.10, 0.17+/-0.14 and 0.18+/-0.10, respectively. Therefore, the expression
      levels of these genes were significantly greater in CC compared with healthy
      cervical tissue (P<0.05). mRNA expression levels of MRD1 were increased in the
      well differentiated group (0.68+/-0.27) compared with the poorly differentiated
      group (0.38+/-0.33; P<0.05). No significant differences were observed between LRP
      and GSTP1 mRNA expression levels and tumor differentiation or clinical stage of
      the patients (P>0.05). Multivariate logistic regression indicated that the degree
      of differentiation and the MDR1 gene expression levels were predictors of CC
      prognosis (P<0.05). The survival rate of patients in the MDR1-negative group was
      significantly greater compared with the MDR1-positive group (P<0.05). The results
      of the present study therefore suggested that MDR1 gene expression is a predictor
      of poor survival in CC.

PMID- 28447726
TI  - A three-caller pipeline for variant analysis of cancer whole-exome sequencing
      data.
AB  - Rapid advancements in next generation sequencing (NGS) technologies, coupled with
      the dramatic decrease in cost, have made NGS one of the leading approaches
      applied in cancer research. In addition, it is increasingly used in clinical
      practice for cancer diagnosis and treatment. Somatic (cancer-only) single
      nucleotide variants and small insertions and deletions (indels) are the simplest
      classes of mutation, however, their identification in whole exome sequencing data
      is complicated by germline polymorphisms, tumor heterogeneity and errors in
      sequencing and analysis. An increasing number of software and methodological
      guidelines are being published for the analysis of sequencing data. Usually, the
      algorithms of MuTect, VarScan and Genome Analysis Toolkit are applied to identify
      the variants. However, one of these algorithms alone results in incomplete
      genomic information. To address this issue, the present study developed a
      systematic pipeline for analyzing the whole exome sequencing data of
      hepatocellular carcinoma (HCC) using a combination of the three algorithms, named
      the three-caller pipeline. Application of the three-caller pipeline to the whole
      exome data of HCC, improved the detection of true positive mutations and a total
      of 75 tumor-specific somatic variants were identified. Functional enrichment
      analysis revealed the mutations in the genes encoding cell adhesion and
      regulation of Ras GTPase activity. This pipeline provides an effective approach
      to identify variants from NGS data for subsequent functional analyses.

PMID- 28447727
TI  - Advanced glycation end products-induced mitochondrial energy metabolism
      dysfunction alters proliferation of human umbilical vein endothelial cells.
AB  - Advanced glycation end products (AGEs) restrain the proliferation of endothelial
      cells, which is an important determinant of diabetic vasculopathy. Mitochondrial
      biogenesis serves an essential role in cellular adaptation and repair. The
      current study aimed to investigate alterations in mitochondrial energy metabolism
      in human umbilical vein endothelial cells (HUVECs) and the latent mechanism
      regulated by AGEs. The proliferation of cultured HUVECs stimulated with AGEs was
      detected using an MTT assay and a real-time cell analyzer (RTCA). Mitochondrial
      energy metabolism was measured using a Seahorse metabolic flux analyzer.
      Mitochondrial membrane potential was detected under fluorescence microscopy
      following staining with tetraethylrhodamine and MitoTracker Red. Respiratory
      chain complexes I-V were detected using western blotting. MTT and RTCA assays
      demonstrated that AGEs treatment significantly inhibited the viability and
      proliferation of HUVECs when compared with bovine serum albumin treatment.
      Results from the Seahorse metabolic flux analyzer indicated that mitochondrial
      aerobic respiration and glycolysis declined following AGEs treatment. In
      addition, mitochondrial membrane potential and the expression of mitochondrial
      respiration chain complexes I/II/III/IV/V notably decreased in the presence of
      AGEs. In conclusion, the results of the present study indicated that AGEs
      exhibited an inhibitory effect on the proliferation in HUVECs potentially by
      mediating the dysfunction of mitochondrial energy metabolism and glycolysis. This
      may provide a new consideration for therapeutic methods in diabetic vascular
      complications.

PMID- 28447728
TI  - High expression of ubiquitin-specific peptidase 39 is associated with the
      development of vascular remodeling.
AB  - Vascular remodeling is the primary cause underlying the failure of angioplasty
      surgeries, including vascular stenting, transplant vasculopathy and vein grafts.
      Multiple restenosis-associated proteins and genes have been identified to account
      for this. In the present study, the functions of ubiquitin-specific peptidase 39
      (USP39) were investigated in the context of two vascular remodeling models (a
      mouse common carotid artery ligation and a pig bilateral saphenous vein-carotid
      artery interposition graft). USP39 has previously been observed to be upregulated
      in ligated arteries, and this result was confirmed in the pig vein graft model.
      In addition, Transwell assay results demonstrated that vascular smooth muscle
      cell (VSMC) migration was suppressed by lentiviral vector-mediated downregulation
      of USP39 and enhanced by upregulation of USP39. Furthermore, knockdown of USP39
      inhibited VSMC cell proliferation and the expression of cyclin D1 and cyclin
      dependent kinase 4, as analyzed via cell counting, MTT assay and western
      blotting. These results suggest that USP39 may represent a novel therapeutic
      target for treating vascular injury and preventing vein-graft failure.

PMID- 28447729
TI  - Effects of endoplasmic reticulum stress on apoptosis induction in radioresistant
      macrophages.
AB  - Macrophages are important in the host's immune defense against pathogens.
      However, recent evidence has demonstrated that macrophages are also involved in
      the development of disease, including cancer. Therefore, it is important to
      regulate apoptosis in tumor-related macrophages for effective cancer treatment.
      In the present study, the effect of endoplasmic reticulum (ER) stress on
      apoptosis induction was examined in human monocytic cell-derived macrophages.
      Radiation therapy in cancer results in irradiating macrophages as well as cancer
      cells in the tumor microenvironment. Since ER stress has been demonstrated to
      sensitize cancer cells to radiation, it was hypothesized that ER stress may
      induce a similar effect in macrophages. Therefore, the effect of combination
      treatment with ER stress inducers and ionizing radiation on macrophage apoptosis
      was examined. Treatment of macrophages with ER stress inducers thapsigargin and
      tunicamycin, enhanced unfolded protein responses, including phosphorylation of
      eukaryotic initiation factor 2-alpha and increased expression of binding
      immunoglobulin protein. Furthermore, treatment with thapsigargin and tunicamycin
      induced apoptosis in macrophages compared with untreated cells, although ionizing
      radiation did not. The thapsigargin-induced apoptosis in macrophages was
      demonstrated to be caspase-3-dependent. Finally, combination treatment with
      thapsigargin and ionizing radiation, did not result in any significant change in
      macrophage apoptosis. The present study demonstrated that ER stress regulated
      apoptosis in radioresistant macrophages and that ionizing radiation had no added
      effect on ER stress-induced apoptosis in macrophages.

PMID- 28447730
TI  - Pioglitazone ameliorates Abeta42 deposition in rats with diet-induced insulin
      resistance associated with AKT/GSK3beta activation.
AB  - Pioglitazone may have potential benefits as an alternative therapeutic treatment
      for patients with Alzheimer's disease (AD), particularly in individuals that also
      have comorbid diabetes; however, the mechanisms of action remain unclear. The
      present study aimed to explore the effects of pioglitazone on amyloid beta,
      isoform 42 (Abeta42) deposition in rats with diet-induced insulin resistance
      (IR). Diet-induced IR model rats were established in the presence or absence of
      pioglitazone. Plasma glucose and insulin levels, and cerebrospinal fluid insulin
      levels were measured; in addition, hippocampal tissues were collected for
      immunohistochemical analysis of Abeta42 expression. The levels of insulin
      degrading enzyme (IDE) and peroxisome proliferator-activated receptor gamma
      (PPARgamma) mRNA and protein expression were analyzed by reverse transcription
      quantitative polymerase chain reaction and western blotting, respectively. In
      addition, the activation of glycogen synthase kinase 3beta (GSK3beta) induced by
      phosphatidylinositol 3-kinase (PI3K) /protein kinase B (AKT) signaling was
      detected by western blotting. Results from the present study demonstrated that
      pioglitazone may enhance peripheral and brain insulin sensitivity in diet-induced
      IR model rats. Treatment with pioglitazone ameliorated Abeta42 deposition in the
      hippocampus by increasing IDE and PPARgamma expression. Notably, activation of
      the PI3K/AKT/GSK3beta pathway was also demonstrated to serve a role in
      pioglitazone-induced Abeta42 degradation, which was abrogated by the PPARgamma
      antagonist GW9662. Results from the present study indicated that pioglitazone may
      improve insulin sensitivity and ameliorate Abeta42 accumulation in rats with diet
      induced IR by regulating AKT/GSK3beta activation, suggesting that pioglitazone
      may be a promising drug for AD treatment.

PMID- 28447731
TI  - Vatalanib, a tyrosine kinase inhibitor, decreases hepatic fibrosis and sinusoidal
      capillarization in CCl4-induced fibrotic mice.
AB  - Among the various consequence arising from lung injury, hepatic fibrosis is the
      most severe. Decreasing the effects of hepatic fibrosis remains one of the
      primary therapeutic challenges in hepatology. Dysfunction of hepatic sinusoidal
      endothelial cells is considered to be one of the initial events that occur in
      liver injury. Vascular endothelial growth factor signaling is involved in the
      progression of genotype changes. The aim of the present study was to determine
      the effect of the tyrosine kinase inhibitor, vatalanib, on hepatic fibrosis and
      hepatic sinusoidal capillarization in a carbon tetrachloride (CCl4)-induced mouse
      model of liver fibrosis. Liver fibrosis was induced in BALB/c mice using CCl4 by
      intraperitoneal injection for 6 weeks. The four experimental groups included a
      control, and three experimental groups involving administration of CCl4,
      vatalanib and a combination of the two. Histopathological staining and measuring
      live hydroxyproline content evaluated the extent of liver fibrosis. The
      expression of alpha-smooth muscle actin (SMA) and cluster of differentiation (CD)
      34 was detected by immunohistochemistry. Collagen type I, alpha-SMA, transforming
      growth factor (TGF)-beta1 and vascular endothelial growth factor receptor (VEGFR)
      expression levels were measured by reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR). The average number of fenestrae per hepatic sinusoid
      was determined using transmission electron microscopy. Liver fibrosis scores and
      hydroxyproline content were decreased in both vatalanib groups. In addition, both
      doses of vatalanib decreased mRNA expression levels of hepatic alpha-SMA, TGF
      beta1, collagen-1, VEGFR1, and VEGFR2. Levels of alpha-SMA and CD34 protein were
      decreased in the vatalanib group compared with the CCl4 group. There were
      significant differences in the number of fenestrae per sinusoid between the
      groups. The present study identified that administration of vatalanib was
      associated with decreased liver fibrosis and hepatic sinusoidal capillarization
      in CCl4-induced mouse models, and is a potential compound for counteracting liver
      fibrosis.

PMID- 28447732
TI  - Icariin inhibits MMP-1, MMP-3 and MMP-13 expression through MAPK pathways in IL
      1beta-stimulated SW1353 chondrosarcoma cells.
AB  - Osteoarthritis (OA) is the most common type of arthritis and is a leading cause
      of disability worldwide, resulting in pain, reduced quality of life and
      socioeconomic burden. Current therapies for OA focus on mitigating the symptoms
      of advanced disease, but novel therapeutic agents are needed to inhibit the
      processes leading to OA. The present study aimed to investigate the effects of
      Icariin on matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13 expression in
      interleukin (IL)-1beta-stimulated human SW1353 chondrosarcoma cells, and to
      investigate the possible mechanism underlying the chondroprotective effects of
      Icariin. In the present study, IL-1beta was applied on SW1353 chondrosarcoma
      cells to mimic the microenvironment of osteoarthritis. The cells were treated
      with Icariin and mitogen-activated protein kinase (MAPK) signaling pathway
      activators or inhibitors. MMP-1, MMP-3, MMP-13, phosphorylated (P)-p38, P-c-Jun N
      terminal kinase (JNK) and P-extracellular signal-regulated kinase (ERK)
      expression was assessed using reverse transcription-quantitative polymerase chain
      reaction, ELISA and western blot analysis. The results of the present study
      demonstrated that Icariin inhibited the expression of MMP-1, MMP-3, MMP-13, P
      p38, P-ERK and P-JNK. Furthermore, it was revealed that the inhibition of p38 and
      ERK contributed to the inhibition of MMP-1 and MMP-3 by Icariin, whereas the
      inhibition of p38 and JNK contributed to the inhibition of MMP-13. The present
      results suggested that Icariin may have a chondroprotective effect, exerted
      through the inhibition of MMP-1, MMP-3 and MMP-13 via MAPK pathways. Therefore,
      Icariin may have potential as a novel therapeutic strategy for the treatment of
      osteoarthritis.

PMID- 28447733
TI  - Gene expression profile in human induced pluripotent stem cells: Chondrogenic
      differentiation in vitro, part B.
AB  - The development of human induced pluripotent stem cells (hiPSCs) is considered a
      turning point in tissue engineering. However, more data are required to improve
      understanding of key aspects of the cell differentiation process, including how
      specific chondrogenic processes affect the gene expression profile of chondrocyte
      like cells and the relative value of cell differentiation markers. The main aims
      of the present study were as follows: To determine the gene expression profile of
      chondrogenic-like cells derived from hiPSCs cultured in mediums conditioned with
      HC-402-05a cells or supplemented with transforming growth factor beta3 (TGF
      beta3), and to assess the relative utility of the most commonly-used chondrogenic
      markers as indicators of cell differentiation. These issues are relevant with
      regard to the use of human fibroblasts in the reprogramming process to obtain
      hiPSCs. Human fibroblasts are derived from mesoderm and thus share a wide range
      of properties with chondrocytes, which originate from the mesenchyme. The hiPSCs
      were obtained from human primary dermal fibroblasts during a reprogramming
      process. Two methods, both involving embryoid bodies (EB), were used to obtain
      chondrocytes from the hiPSCs: EBs formed in the presence of a chondrogenic medium
      with TGF-beta3 (10 ng/ml) and EBs formed in a medium conditioned with growth
      factors from HC-402-05a cells. Based on reverse transcription-quantitative
      polymerase chain reaction analysis, the results demonstrated that hiPSCs are
      capable of effective chondrogenic differentiation, with the cells obtained in the
      HC-402-05a medium presenting with morphological features and markers
      characteristic of mature human chondrocytes. In contrast, cells differentiated in
      the presence of TGF-beta3 presented with certain undesirable hypertrophic
      characteristics. Several genes, most notably runt-related transcription factor 2,
      transforming growth factor beta2 and transforming growth factor beta3, were good
      markers of advanced and late hiPSC chondrogenic differentiation, whereas
      transforming growth factor beta3I, II, III receptors and bone morphogenetic
      protein-2, bone morphogenetic protein-4 and growth differentiation factor 5 were
      less valuable. These findings provide valuable data on the use of stem cells in
      cartilage tissue regeneration.

PMID- 28447734
TI  - High glucose promotes the osteogenic differentiation capability of human
      periodontal ligament fibroblasts.
AB  - Periodontal ligament fibroblasts (PDLFs) are important cells, which are involved
      in maintaining tooth integrity. Diabetes has been found to be associated with
      periodontal disease in a bidirectional manner. The aim of the present study was
      to investigate the stemness properties of human PDLFs (HPDLFs) in high glucose
      conditions. HPDLFs were analyzed for their osteogenic differentiation capacity by
      inducing the cells with osteogenic medium in various glucose concentrations. The
      gene expression was then examined using reverse transcription-quantitative
      polymerase chain reaction analysis, and examinations of alkaline phosphatase
      activity and nodule formation were performed. The results of the gene expression
      analysis revealed that high glucose media induced the expression of NANOG,
      octamer-binding transcription factor 4, (sex determining region Y)-box 2, cluster
      of differentiation 166 (CD166), PERIOSTIN and beta-CATENIN following culture of
      the cells for 3 days. Alkaline phosphatase activity increased following 14 days
      in the high glucose condition. In addition, higher numbers of calcified nodules
      were formed on day 28 in the group cultured with high glucose. The results showed
      that high glucose induced bone formation by elevating the expression of stem cell
      markers, particularly CD166, and this induction may be regulated through beta
      CATENIN.

PMID- 28447735
TI  - Mice endometrium receptivity in early pregnancy is impaired by maternal
      hyperinsulinemia.
AB  - Previous studies have investigated the lower embryo implantation rates in women
      with polycystic ovary syndrome, obesity and type 2 diabetes, and specifically the
      association between the abnormal oocyte and embryo and hyperinsulinemia. The
      importance of hyperinsulinemia on maternal endometrium receptivity remains to be
      elucidated. The present study used a hyperinsulinemic mouse model to determine
      whether hyperinsulinemia may affect endometrial receptivity. An insulin
      intervention mouse model was first established. The serum levels of insulin,
      progesterone and estradiol were subsequently detected by ELISA assay analysis.
      The number of implantation sites was recorded using Trypan blue dye and the
      morphology of mice uteri was investigated using hematoxylin and eosin staining.
      The expression levels of molecular markers associated with endometrial
      receptivity were detected by reverse transcription-quantitative polymerase chain
      reaction, western blotting and immunohistochemistry analyses. Finally, the
      importance of mechanistic target of rapamycin (mTOR) expression following insulin
      treatment was determined. Mice treated with insulin developed insulin resistance
      and hyperinsulinemia. The number of implantation sites following insulin
      treatment did not differ between the control and insulin-treated groups.
      Additionally, no significant morphological alterations in mice uteri between
      control and insulin-treated groups were observed. However, the expression levels
      of estrogen receptor (Esr) 1, Esr2, progesterone receptor and homeobox A10
      associated with endometrial receptivity, were imbalanced during endometrium
      receptivity when maternal hyperinsulinemia was induced. Western blot analysis
      revealed that expression levels of endometrial phosphorylated (p)-mTOR and p
      ribosomal protein S6 kinase beta-1 were significantly greater in the insulin
      treated group. These results demonstrated that although an embryo may implant
      into endometrium, mice endometrium receptivity in early pregnancy may be impaired
      by maternal hyperinsulinemia. In addition, mTOR signaling may be involved in this
      process. The present study provides preliminary results demonstrating that female
      reproduction may be compromised during hyperinsulinemia, which requires further
      investigation in future studies.

PMID- 28447736
TI  - Investigation of hypoglycemic, hypolipidemic and anti-nephritic activities of
      Paecilomyces tenuipesN45 in diet/streptozotocin-induced diabetic rats.
AB  - Due to its pharmacological activities, Paecilomyces tenuipes has previously been
      used as a folk medicine in Asia. The primary aim of the present study was to
      investigate the hypoglycemic, hypolipidemic and anti-nephritic effects of P.
      tenuipes N45 aqueous extracts (PTNE) in a high fat diet/streptozotocin-induced
      diabetic rat model. The rats were treated with 120 mg/kg of metformin or 0.04,
      0.2 or 1.0 g/kg PTNE for 4 weeks. The hypoglycemic activity of PTNE was confirmed
      by the observation of reduced fasting blood glucose level and by partially
      normalized oral glucose tolerance. PTNE reduced total cholesterol and
      triglyceride content, and balanced the levels of low-density and high-density
      lipoproteins. The suppressive effects of PTNE on creatinine, blood urea nitrogen,
      interleukin (IL)-2, IL-6 and nuclear factor-kappaB levels indicated its ability
      to provide protection against diabetic nephropathy. PTNE treatment increased
      superoxide dismutase, malondialdehyde and glutathione peroxidase levels,
      suggesting that its anti-diabetic and anti-nephropathic activities may be
      associated with the prevention of oxidative damage during type 2 diabetic
      mellitus. The findings of the present study provided experimental evidence for
      the application of Paecilomyces tenuipes N45 on the treatment of type 2 diabetic
      mellitus.

PMID- 28447737
TI  - 17beta-estradiol protects against doxorubicin-induced cardiotoxicity in male
      Sprague-Dawley rats by regulating NADPH oxidase and apoptosis genes.
AB  - Doxorubicin (DOX) is one of the most effective chemotherapeutic agents for the
      treatment of a number of malignancies. However, its use is limited by serious
      cardiotoxic effects, for which there are currently no reliable pharmacologic
      therapies. Estrogen has exhibited protective effects against cardiac stressors in
      male and female animal models; however, its effects on DOX-induced cardiotoxicity
      remain unknown. High mortality and morbidity rates have been observed in patients
      with cancer worldwide, and DOX is often administered to a greater number of men
      than women. Therefore, the present study employed male Sprague-Dawley rats to
      evaluate the protective effects of 17beta-estradiol (E2) against DOX-induced
      cardiotoxicity. A total of 4 mg/kg DOX was administered to 14-week-old male
      Sprague-Dawley rats by intraperitoneal injection twice a week for 2 weeks. At 3
      weeks following the first injection of DOX, an echocardiographic study revealed
      that DOX administration significantly decreased cardiac ejection fraction and
      fractional shortening by 20 and 29%, respectively, when compared with the vehicle
      treated control rats (P<0.05). This was associated with decreased heart weight,
      myofibrillar disorganization and myofiber loss. The serum biomarkers for heart
      injury, including alanine aminotransferase, aspartate aminotransferase, lactate
      dehydrogenase and creatine kinase, were increased in DOX vs. vehicle-treated rats
      (P<0.05). E2 treatment by a daily subcutaneous injection of 2 mg/kg body weight
      attenuated the cardiotoxic effects of DOX. In addition, E2 treatment inhibited
      the DOX-induced increase in the expression of cardiac genes, nicotinamide adenine
      dinucleotide phosphate oxidase (NOX) 2, NOX4, B-cell lymphoma 2-associated X
      protein and caspase 3. These results demonstrate that E2 treatment may protect
      the heart against DOX-induced cardiotoxicity in male rats potentially through the
      regulation of NOX2, NOX4 and apoptosis genes.

PMID- 28447738
TI  - Telmisartan suppresses cardiac hypertrophy by inhibiting cardiomyocyte apoptosis
      via the NFAT/ANP/BNP signaling pathway.
AB  - Telmisartan, a type of angiotensin II (Ang II) receptor inhibitor, is a common
      agent used to treat hypertension in the clinic. Hypertension increases cardiac
      afterload and promotes cardiac hypertrophy. However, the ventricular Ang II
      receptor may be activated in the absence of hypertension. Therefore, telmisartan
      may reduce cardiac hypertrophy by indirectly ameliorating hypertensive symptoms
      and directly inhibiting the cardiac Ang II receptor. Nuclear factor of activated
      T-cells (NFAT) contributes to cardiac hypertrophy via nuclear translocation,
      which induces a cascade of atrial natriuretic peptide (ANP) and brain/B-type
      natriuretic peptide (BNP) expression and cardiomyocyte apoptosis. However, NFAT
      mediated inhibition of cardiac hypertrophy by telmisartan remains poorly
      understood. The present study demonstrated that telmisartan suppressed
      cardiomyocyte hypertrophy in a mouse model of cardiac afterload and in cultured
      cardiomyocytes by inhibiting NFAT nuclear translocation, as well as by inhibiting
      ANP and BNP expression and cardiomyocyte apoptosis, in a dose-dependent manner.
      The present study provides a novel insight into the potential underlying
      mechanisms of telmisartan-induced inhibition of cardiomyocyte hypertrophy, which
      involves inhibition of NFAT activation, nuclear translocation and the ANP/BNP
      cascade.

PMID- 28447739
TI  - Neural precursor cell expressed, developmentally downregulated 8-activating
      enzyme inhibitor MLN4924 sensitizes colorectal cancer cells to oxaliplatin by
      inducing DNA damage, G2 cell cycle arrest and apoptosis.
AB  - Oxaliplatin-based chemotherapy is a primary treatment for patients with
      metastatic colorectal cancer (CRC); however, its efficacy is limited. Therefore,
      novel therapeutic agents are urgently required. MLN4924 is a first-in-class
      inhibitor of neural precursor cell expressed, developmentally downregulated 8
      (NEDD8)-activating enzyme E1, and has entered various phase-I/II clinical trials
      for cancer therapy due to its significant anticancer efficacy. The aim of the
      present study was to examine the synergistic effect and underlying mechanisms of
      MLN4924 and oxaliplatin combined treatment for CRC. It was demonstrated that
      MLN4924 treatment induced the DNA damage response (DDR) by inactivating cullin
      ring ubiquitin ligases, subsequently leading to cell cycle disturbance and
      apoptosis in CRC cells. MLN4924 treatment increased the oxaliplatin-induced DDR,
      G2 cell cycle arrest and apoptosis. Protein expression levels of phosphorylated
      checkpoint kinase 2 (p-CHK2), p21 and p53, which are well-known functional
      proteins involved in G2 cell cycle arrest, were assessed. p-CHK2 protein
      expression levels were increased following combined treatment with MLN4924 and
      oxaliplatin, whereas p21/p53 protein expression levels were not. In conclusion,
      MLN4924 treatment may sensitize CRC cells to oxaliplatin treatment by inducing
      the DDR and increasing protein expression levels of p-CHK2, leading to G2 cell
      cycle arrest and apoptosis. Therefore, combined MLN4924 and oxaliplatin-based
      chemotherapy may be a potential therapeutic strategy for the treatment of CRC.

PMID- 28447740
TI  - Calyptranthes grandifolia O.Berg (Myrtaceae) ethanolic extract inhibits TNF-alpha
      gene expression and cytokine release in vitro.
AB  - Anti-tumor therapies based on anti-inflammatory effects have been considered in
      cancer treatment. Survival, proliferation and, resultantly, invasion and
      metastasis of tumor cells are regulated by local inflammatory mediators. Primary
      inflammatory cytokines, such as tumor necrosis factor (TNF), are targets for
      anticancer therapy. Several anti-inflammatory agents isolated from natural
      products are becoming important chemopreventive and therapeutic agents for
      cancer. The present study aimed to investigate the expression of TNF-alpha,
      nuclear factor-kappaBeta (NF-kappaBeta) and p38alpha mitogen-activated protein
      kinase (p38alpha) genes, associated with proliferation and inflammation in the
      Caco-2 cell line treated with ethanolic and hexanic extracts of Calyptranthes
      grandifolia O.Berg (Myrtaceae). Caco-2 cells were cultured and treated with plant
      extract at different concentrations (25, 50, 100 and 200 ug/ml) and stimulated
      with lipopolysaccharide (LPS). For gene expression, analysis was performed by
      total RNA extraction followed by synthesis of complementary DNA and analysis by
      quantitative polymerase chain reaction. The release of TNF-alpha cytokine was
      evaluated by ELISA in RAW 264.7 murine macrophages activated by LPS. Among the
      evaluated genes, there was a decrease in TNF-alpha expression at 100 and 200
      ug/ml concentrations only with the ethanolic extract (P<0.025). The p38alpha gene
      exhibited a tendency to increase expression only when treated with ethanolic
      extract and the NF-kappaBeta gene did not significantly differ compared with the
      positive control when treated with either analyzed extract. The inhibition of TNF
      alpha cytokine in the RAW 264.7 cell line was significant (P<0.05) in ethanolic
      extract at 200 ug/ml compared with the positive control (LPS 1 ug/ml). In
      conclusion, the ethanolic extract may exhibit an anti-inflammatory activity by
      inhibiting TNF-alpha. However, further studies are required to confirm its
      potential anti-inflammatory effects.

PMID- 28447741
TI  - Effect of isosecotanapartholide isolated from Artemisia princeps Pampanini on IL
      33 production and STAT-1 activation in HaCaT keratinocytes.
AB  - The present study aimed to investigate the anti-inflammatory effect and mechanism
      of action of isosecotanapartholide (ISTP), isolated from Artemisia princeps
      Pampanini extract (APE). The effects of ISTP and APE on the proliferation of
      human keratinocytes following stimulation by tumor necrosis factor
      alpha/interferon-gamma were assessed. ISTP and APE downregulated the expression
      levels of signal transducer and activator of transcription-1 (STAT-1), and
      reduced interleukin-33 (IL-33) production. ISTP and APE inhibited the mRNA
      expression levels of thymus and activation-regulated chemokine (TARC/CCL17) in a
      dose-dependent manner. Western blot analysis demonstrated that ISTP and APE dose
      dependently inhibited protein expression levels of intercellular adhesion
      molecule-1 and phosphorylation of STAT-1. The results of the present study
      indicate that ISTP may inhibit TARC/CCL17 production in human epidermal
      keratinocytes via the STAT-1 signaling pathway and may be associated with the
      inhibition of IL-33 production. The current study indicated that ISTP is an
      active component in APE and may be a potential therapeutic agent for the
      treatment of inflammatory skin disorders.

PMID- 28447742
TI  - Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats
      during fracture healing.
AB  - Fracture healing involves the coordinated actions of multiple cytokines. Bone
      morphogenetic protein 9 (BMP9) is an important factor in bone formation. The
      present study aimed to investigate the osteogenic potential of bone marrow stem
      cells (BMSCs) in response to adenoviral (Ad)BMP9, and the early fracture repair
      properties of AdBMP9 in surgically-created fractures in osteoporotic rats.
      Alkaline phosphatase (ALP) activity was assayed and matrix mineralization was
      examined by Alizarin Red S staining. mRNA and protein expression levels of BMP9,
      runt-related transcription factor 2 (RUNX2) and type 1 collagen (COL-1) were
      detected in vitro and in vivo. Femoral bone mineral density was assessed for
      osteoporosis in ovariectomized rats. An open femora fracture was subsequently
      created, and gelatin sponges containing AdBMP9 were implanted. The femora were
      harvested for radiographical, micro-computed tomography, biomechanical and
      histological analysis 4 weeks later. BMP9 successfully increased ALP activity and
      induced mineralized nodule formation in BMSCs. BMP9 in gelatin sponges
      demonstrated marked effects on microstructural parameters and the biomechanical
      strength of bone callus. In addition, it upregulated the expression levels of
      RUNX2 and COL-1. AdBMP9 in gelatin sponges significantly mediated callus
      formation, and increased bone mass and strength in osteoporotic rats with femora
      fractures. The results of the present study suggested that BMP9 enhanced callus
      formation and maintained early mechanical stability during fracture healing in
      osteoporotic rats, implicating it as a potential novel therapeutic target for
      fracture healing.

PMID- 28447744
TI  - Cyclic compression stimulates osteoblast differentiation via activation of the
      Wnt/beta-catenin signaling pathway.
AB  - It is widely accepted that mechanical stress is an important factor in bone
      associated cell differentiation, including that of mesenchymal stem cells,
      osteoblasts and osteocytes. The present study aimed to determine the effect of
      mechanical cyclic compressive load on osteoblast differentiation, and whether
      this was associated with activation of the wingless-type (Wnt)/beta-catenin
      signaling pathway. Using a 3D scaffold model, MC3T3-E1 cells were exposed to
      cyclic compressive loading via the Flexcell-5000CTM Compression system.
      Sinusoidal wave magnitudes of 0.33, 0.5 and 1 MPa were applied for 4, 6 and 8 h,
      at 1 Hz frequency. Expression levels of genes associated with osteoblast
      differentiation were enhanced following compression, including alkaline
      phosphatase, osteocalcin, runt-related transcription factor 2 and osterix.
      Optimal compression was observed using a magnitude of 0.5 MPa for 6 h, whereas a
      magnitude of 1 MPa had no effect on osteoblast differentiation, and had a
      negative effect when applied for prolonged time periods. Compressive loading
      additionally enhanced the mRNA expression levels of the Wnt/beta-catenin
      signaling pathway component, low density lipoprotein receptor-related protein 5,
      and the protein expression levels of Wnt1, disheveled segment polarity protein-2
      (DVL2) and beta-catenin. By contrast, mRNA expression levels of sclerostin and
      the inactive form of beta-catenin (phosphorylated at Ser33/37/Thr41) were reduced
      following compressive loading. Following compressive loading of cells, dickkopf
      related protein 1 (DKK-1), an inhibitor of the Wnt signaling pathway, increased
      protein expression levels of the inactive form of the Wnt-associated protein,
      phosphorylated-beta-catenin, compared with compression alone. However, DVL2 and
      Wnt1 protein expression levels were unaffected, suggesting that the loading
      induced activation of Wnt/beta-catenin signaling decreased however, it was not
      prevented by DKK-1 treatment. In conclusion, the present study demonstrated that
      cyclic compressive load promoted osteoblast differentiation and may be dependent
      on the Wnt/beta-catenin signaling pathway in regard to magnitude and duration.

PMID- 28447743
TI  - Binding of circulating anti-MUC1 antibody and serum MUC1 antigen in stage IV
      breast cancer.
AB  - The present study aimed to investigate the binding of circulating mucin 1 (MUC1)
      antibody with serum MUC1 antigen in stage IV breast cancer. Serum samples of 61
      patients with stage IV breast cancer and 64 patients with early-stage breast
      cancer were collected. The anti-MUC1 antibody (IgG) and MUC1 antigen (cancer
      antigen 15-3; Ca15-3) were detected using an indirect enzyme-linked immunosorbent
      assay (I-ELISA) and ELISA, respectively. The MUC1 IgG affinity was detected using
      a urea degradation combining ELISA. Western blot analysis and an inhibition test
      were performed for verification of the binding of anti-MUC1 IgG with MUC1
      antigen, and their correlation was analyzed. The results showed that there was a
      negative correlation between anti-MUC1 IgG and CA15-3 antigen in stage IV breast
      cancer when positive CA15-3 antigen and/or anti-MUC1 IgG were selected (r=-0.417;
      P=0.0044). The positive anti-MUC1 IgG with positive Ca15-3 antigen was more
      common in stage IV breast cancer, compared with early-stage breast cancer
      (chi2=4.629; P=0.031), however, Ca15-3 antigen positivity was higher in stage IV
      breast cancer, compared with early-stage breast cancer (chi2=10.58; P=0.001).
      Anti-MUC1 IgG was able to bind to the MUC1 antigen in stage IV breast cancer. No
      differences in the 8R-MUCPT inhibition ratio were found between the two groups
      (P=0.778), and there were no differences in the affinity of anti-MUC1 IgG
      (P=0.873). In stage IV breast cancer, circulating anti-MUC1 antibody was found to
      bind serum MUC1 antigen, although their compatibility was low. No significant
      difference was found in the affinity of the anti-MUC1 antibody between stage IV
      breast cancer and early-stage breast cancer.

PMID- 28447745
TI  - Association between myocardial cell apoptosis and calpain-1/caspase-3 expression
      in rats with hypoxic-ischemic brain damage.
AB  - The present study aimed to investigate the association between myocardial cell
      apoptosis and calpain-1/caspase-3 expression in a rat model of hypoxic-ischemic
      brain damage (HIBD). A total of 64 newborn rats were divided into control (n=8;
      sacrificed on day 7) and HIBD groups (n=56). HIBD group rats were sacrificed 2,
      12 or 24 h, or 2, 3, 5 or 7 days following HIBD (n=8/group). A terminal
      deoxynucleotidyl transferase dUTP nick-end labeling assay was performed to detect
      myocardial apoptotic cells and calculate the apoptosis index (AI), reverse
      transcription-polymerase chain reaction was performed to detect myocardial
      calpain-1/caspase-3 mRNA expression levels and a western blot analysis was
      conducted to detect calpain-1 protein expression levels. The correlations between
      calpain-1 and caspase-3 expression levels and AI were analyzed. The results
      demonstrated that apoptotic myocardial cells in the HIBD groups were markedly
      increased compared with the control group, with AI peaking in the day 3 group.
      Caspase-3 and calpain-1 mRNA expression levels were increased from 2 and 12 h
      following HIBD, respectively, with the most elevated levels in the day 2 group.
      Compared with the control group, calpain-1 protein expression levels were
      increased from 2 h, with the greatest expression levels in the day 3 group
      (P<0.05). Calpain-1 mRNA and protein (76/80 kDa) expression levels demonstrated
      positive linear correlations with AI (r=0.786, P=0.001; and r=0.853, P=0.001,
      respectively) Caspase-3 mRNA expression levels were positively correlated with AI
      (r=0.894; P=0.001). In conclusion, the present study demonstrated that in rats
      with HIBD, there is a positive correlation between increased apoptosis of
      myocardial cells and expression levels of calpain-1 and caspase-3.

PMID- 28447746
TI  - [Retracted] Regulatory T cells exhibit neuroprotective effect in a mouse model of
      traumatic brain injury.
AB  - We would like to retract our article entitled 'Regulatory T cells exhibit
      neuroprotective effect in a mouse model of traumatic brain injury' published in
      Molecular Medicine Reports 14: 5556-5566, 2016. After careful consideration, we
      recognize that there was an undeclared conflict of interest on the part of
      certain of the authors. All the authors agree to this retraction. We sincerely
      apologize for any inconvenience that might result from the retraction of this
      article. [The original article was published in Molecular Medicine Reports 14:
      5556-5566, 2016; DOI: 10.3892/mmr.2016.5954].

PMID- 28447747
TI  - Lycium barbarum polysaccharide exhibits cardioprotection in an experimental model
      of ischemia-reperfusion damage.
AB  - Cardiovascular diseases are a major cause of mortality and disability worldwide.
      The present study investigated the cardio-protective effects of polysaccharides
      extracted from Lycium barbarum (LB), the fruit of which is traditionally used in
      Chinese medicine. Polysaccharides were characterized using Fourier transform
      infrared spectroscopy and high-performance liquid chromatography techniques. The
      present study demonstrated that LB polysaccharides are composed of glucose and
      fructose monosaccharides in a molar ratio of 1:2. A total of 36 rats were divided
      into three groups plus a control group, with nine animals in each group, and were
      used for studying the cardioprotective effects of LB polysaccharides. The low
      dose group received 150 mg/kg body weight (BW) polysaccharides and the high-dose
      group received 300 mg/kg BW polysaccharides. The results demonstrated that the LB
      polysaccharides reduced the levels of myocardial lactate dehydrogenase and
      increased the sodium-potassium ATPase and calcium ATPase activities in rats with
      heart ischemia-reperfusion injury. In addition, there was a decrease in the
      myocardial Bax-positive expression and the rate of myocardial cell apoptosis,
      along with a dose-dependent increase in Bcl-2-positive expression. Therefore, it
      was concluded that LB polysaccharides are able to halt the progression of
      cardiovascular diseases.

PMID- 28447748
TI  - Tenascin-C expression and its associated pathway in BMSCs following co-culture
      with mechanically stretched ligament fibroblasts.
AB  - The occurrence of pelvic organ prolapse (POP) is closely associated with
      alterations in the extracellular matrix proteins of the supporting ligament. Bone
      marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into a
      variety of cell types, including osteoblasts, chondroblasts and adipocytes.
      Therefore, BMSCs have the potential to improve the clinical outcomes of POP.
      Tenascin-C is a large glycoprotein that is present in the ECM and is involved in
      morphogenetic movements, and tissue patterning and repair. The aim of the present
      study was to investigate the effect of mechanical stretching on tenascin-C
      expression during the differentiation of BMSCs induced by pelvic ligament
      fibroblasts. BMSCs were isolated from 7-day-old Sprague Dawley rats. Fibroblasts
      were obtained from rat pelvic ligaments and, at the fourth passage, were
      subjected to 10% deformation with 1 Hz, periodic one-way mechanical stretch
      stimulation, followed by co-culture with BMSCs. The co-culture with stretched
      fibroblasts increased tenascin-C and transforming growth factor (TGF)-beta
      expression levels, compared with groups without mechanical stimulation.
      Neutralizing anti-TGF-beta1 antibodies, and inhibitors of TGF-beta receptor,
      mitogen-activated protein kinase (MAPK) kinase and MAPK, decreased tenascin-C
      expression levels induced by TGF-beta and mechanical stretching. The results of
      the present study suggested that the regulation of tenascin-C expression levels
      in BMSCs co-cultured with mechanically stretched pelvic ligament fibroblasts is
      mediated via the soluble growth factor TGF-beta and the MAPK signaling pathway.
      In addition, these results indicated that in an indirect co-culture system,
      pelvic ligament fibroblasts with mechanical stretch stimulation may promote the
      synthesis of tenascin-C and BMSC differentiation into pelvic ligament
      fibroblasts.

PMID- 28447749
TI  - Dental and periodontal phenotypes of Dlx2 overexpression in mice.
AB  - Distal-less homeobox 2 (Dlx2) is a member of the homeodomain family of
      transcription factors and is important for the development of cranial neural
      crest cells (CNCCs)-derived craniofacial tissues. Previous studies revealed that
      Dlx2 was expressed in the cementum and a targeted null mutation disrupted tooth
      development in mice. However, whether Dlx2 overexpression may impair in vivo
      tooth morphogenesis remains to be elucidated. The present study used a transgenic
      mouse model to specifically overexpress Dlx2 in neural crest cells in order to
      identify the dental phenotypes in mice by observation, micro-computed tomography
      and histological examination. The Dlx2-overexpressed mice exhibited tooth
      abnormalities including incisor cross-bite, shortened tooth roots, increased
      cementum deposition, periodontal ligament disorganization and osteoporotic
      alveolar bone. Therefore, Dlx2 overexpression may alter the alveolar bone,
      cementum and periodontal ligament (PDL) phenotypes in mice.

PMID- 28447750
TI  - Biological effects of bone marrow mesenchymal stem cells on hepatitis B virus in
      vitro.
AB  - The aim of the present study was to explore the effects of co-culturing bone
      marrow-derived mesenchymal stem cells (BM-MSCs) cultured with hepatitis B virus
      (HBV)-infected lymphocytes in vitro. BM-MSCs and lymphocytes from Brown Norway
      rats were obtained from the bone marrow and spleen, respectively. Rats were
      divided into the following five experimental groups: Group 1, splenic lymphocytes
      (SLCs); group 2, HepG2.2.15 cells; group 3, BM-MSCs + HepG2.2.15 cells; group 4,
      SLCs + HepG2.2.15 cells; and group 5, SLCs + BM-MSCs + HepG2.2.15 cells. The
      viability of lymphocytes and HepG2.2.15 cells was assessed using the MTT assay at
      24, 48 and 72 h, respectively. Levels of supernatant HBV DNA and intracellular
      HBV covalently closed circular DNA (cccDNA) were measured using quantitative
      polymerase chain reaction. Supernatant cytokine levels were measured by enzyme
      linked immunosorbent assay (ELISA). T cell subsets were quantified by flow
      cytometry using fluorescence-labeled antibodies. In addition, the HBV genome
      sequence was analyzed by direct gene sequencing. Levels of HBV DNA and cccDNA in
      group 5 were lower when compared with those in group 3 or group 4, with a
      significant difference observed at 48 h. The secretion of interferon-gamma was
      negatively correlated with the level of HBV DNA, whereas secretion of interleukin
      (IL)-10 and IL-22 were positively correlated with the level of HBV DNA. Flow
      cytometry demonstrated that the percentage of CD3+CD8+ T cells was positively
      correlated with the levels of HBV DNA, and the CD3+CD4+/CD3+CD8+ ratio was
      negatively correlated with the level of HBV DNA. Almost no mutations in the HBV
      DNA sequence were detected in HepG2.2.15 cells co-cultured with BM-MSCs, SLCs, or
      in the two types of cells combined. BM-MSCs inhibited the expression of HBV DNA
      and enhanced the clearance of HBV, which may have been mediated by the regulation
      of the Tc1/Tc2 cell balance and the mode of cytokine secretion to modulate
      cytokine expression.

PMID- 28447751
TI  - Deep sea water improves hypercholesterolemia and hepatic lipid accumulation
      through the regulation of hepatic lipid metabolic gene expression.
AB  - A high-fat diet or high-cholesterol diet (HCD) is a major cause of metabolic
      diseases, including obesity and diabetes; vascular diseases, including
      hypertension, stroke and arteriosclerosis; and liver diseases, including hepatic
      steatosis and cirrhosis. The present study aimed to evaluate the effects of deep
      sea water (DSW) on rats fed a HCD. DSW decreased HCD-induced increases in total
      cholesterol and low-density lipoprotein (LDL) cholesterol in the blood, and
      recovered high-density lipoprotein cholesterol. In addition, DSW decreased levels
      of liver injury markers, which were increased in response to HCD, including
      glutamate-oxaloacetate transaminase, glutamate-pyruvate transferase and alkaline
      phosphatase. Lower lipid droplet levels were observed in the livers of rats fed a
      HCD and treated with DSW at a hardness of 1,500, as compared with those in the
      HCD only group. Semi-quantitative reverse transcription-polymerase chain reaction
      (RT-PCR) revealed that mRNA expression levels of fatty acid synthase and sterol
      regulatory element binding protein-1c (SREBP-1c) in rats fed a HCD with DSW were
      lower compared with the HCD only group. Furthermore, quantitative RT-PCR revealed
      that DSW enhanced LDL receptor (LDLR) mRNA expression in a hardness-dependent
      manner. Combined, the results of the present study indicated that DSW may reduce
      HCD-induced increases in blood and liver lipid levels, indicating that DSW may
      protect against hypercholesterolemia and non-alcoholic hepatic steatosis. In
      addition, the present study demonstrated that DSW-induced downregulation of
      lipids in the blood and hepatic lipid accumulation was mediated by enhancement of
      LDLR expression and suppression of fatty acid synthase and SREBP-1c.

PMID- 28447752
TI  - Islet-1 induces the differentiation of mesenchymal stem cells into cardiomyocyte
      like cells through the regulation of Gcn5 and DNMT-1.
AB  - Previous studies from this group demonstrated that insulin gene enhancer binding
      protein ISL-1 (Islet-1) specifically induces the differentiation of mesenchymal
      stem cells (MSCs) into cardiomyocyte-like cells through histone acetylation.
      However, the underlying mechanisms remain unclear. In the present study, the role
      of the histone acetylation and DNA methylation on the regulatory mechanism of the
      Islet-1 was further investigated by methylation-specific polymerase chain
      reaction (PCR), chromatin immunoprecipitation quantitative PCR and western blot
      analysis. The results demonstrated that Islet-1 upregulated expression of general
      control of amino acid biosynthesis protein 5 (Gcn5) and enhanced the binding of
      Gcn5 to the promoters of GATA binding protein 4 (GATA4) and NK2 homeobox 5
      (Nkx2.5). In addition, Islet-1 downregulated DNA methyltransferase (DNMT)-1
      expression and reduced its binding to the GATA4 promoter. In contrast, the amount
      of DNMT-1 binding on Nkx2.5 did not match the expression trend. Therefore, it was
      concluded that Islet-1 may influence the histone acetylation and DNA methylation
      of GATA4 promoter region via Gcn5 and DNMT-1 during the MSC differentiation into
      cardiomyocyte-like cells, thus prompting the expression of GATA4. The Nkx2.5 was
      likely only affected by histone acetylation instead of DNA methylation. The
      present study demonstrated that Islet-1 induces the differentiation of
      mesenchymal stem cells into cardiomyocyte-like cells through a specific
      interaction between histone acetylation and DNA methylation on regulating GATA4.

PMID- 28447753
TI  - Antitumor activity of fucoidan in anaplastic thyroid cancer via apoptosis and
      anti-angiogenesis.
AB  - The present study demonstrated the effect of fucoidan, isolated from Fucus
      vesiculosus, on cell growth and apoptosis in anaplastic thyroid cancer cells. The
      cell viability was analyzed using a Cell Counting Kit-8 cell proliferation kit.
      Diamidino-2-phenylindole and terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling assays were used to examine the apoptotic effect of fucoidan,
      which revealed the presence of apoptotic bodies and DNA fragmentation. Fucoidan
      inhibited the growth of FTC133 and TPC1 ATC cells in a dose-dependent manner. It
      also induced the apoptosis of FTC133 cells by promoting the expression levels of
      cleaved poly ADP-ribose polymerase and caspase-3. Significant decreases in the
      levels expression of hypoxia-inducible factor 1alpha and vascular endothelial
      growth factor were observed in the FTC133 cells following treatment of the cells
      with fucoidan. In addition, inhibition in tube formation and the migration of
      FTC133 cells were observed in the cells treated with fucoidan, compared with the
      cells in the control group. Therefore, fucoidan inhibited cell growth, induced
      apoptosis and suppressed angiogenesis in the thyroid cancer cells.

PMID- 28447754
TI  - Inhibition of heat shock protein 70 intensifies heat-stressed damage and
      apoptosis of chicken primary myocardial cells in vitro.
AB  - To investigate the potential protective effect of heat shock protein 70 (Hsp70)
      during heat stress (HS) in chicken primary myocardial cells (CPMC), a cellular
      model of low expression of Hsp70 was established using 200 uM quercetin, a
      specific inhibitor of Hsp70. Comparative analyses were done among a HS group,
      Hsp70 low expression (HS+Quercetin) group and quercetin treated only group
      (Quercetin) during different durations of HS (0, 1, 2, 3 and 5 h). Inhibition of
      Hsp70 expression in quercetin treatment groups was detected, and suggested that
      Hsp70 expression was inhibited significantly. Levels of enzymes associated with
      cardiac damage were measured. In the Hsp70 low expression group, levels of these
      enzymes were elevated significantly compared with HS group, quercetin alone
      didn't elevate the level of these enzymes, The Hsp70 low expression group had
      twofold greater apoptosis compared with the HS group after 5 h of HS which was
      consistent with the results of Cleaved caspase-3 protein, no obvious apoptosis
      was detected in quercetin group. Levels of caspase-3 and -9 activities were
      significantly higher in the Hsp70 low expression group, no differences of
      apoptosis inducing factor (AIF) in cell nucleus were observed between two groups
      suggested that inhibition of Hsp70 in CPMC increased the percentage of apoptosis
      may involve a mitochondrial pathway but AIF was not included. Expression of Bax
      with Bcl-2 and their downstream cytochrome c in two groups confirmed our
      hypothesis. Our findings suggest that in CPMC, Hsp70 may have a cytoprotective
      role during HS that may act via a mitochondrial pathway.

PMID- 28447755
TI  - Gene expression profile in human induced pluripotent stem cells: Chondrogenic
      differentiation in vitro, part A.
AB  - Human induced pluripotent stem cells (hiPSCs) offer promise in regenerative
      medicine, however more data are required to improve understanding of key aspects
      of the cell differentiation process, including how specific chondrogenic
      processes affect the gene expression profile of chondrocyte-like cells and the
      relative value of cell differentiation markers. The main aims of the present
      study were as follows: To determine the gene expression profile of chondrogenic
      like cells derived from hiPSCs cultured in mediums conditioned with HC-402-05a
      cells or supplemented with transforming growth factor beta3 (TGF-beta3), and to
      assess the relative utility of the most commonly used chondrogenic markers as
      indicators of cell differentiation. These issues are relevant with regard to the
      use of human fibroblasts in the reprogramming process to obtain hiPSCs. Human
      fibroblasts are derived from the mesoderm and thus share a wide range of
      properties with chondrocytes, which also originate from the mesenchyme. Thus, the
      exclusion of dedifferentiation instead of chondrogenic differentiation is
      crucial. The hiPSCs were obtained from human primary dermal fibroblasts during a
      reprogramming process. Two methods, both involving embryoid bodies (EB), were
      used to obtain chondrocytes from the hiPSCs: EBs formed in a chondrogenic medium
      supplemented with TGF-beta3 (10 ng/ml) and EBs formed in a medium conditioned
      with growth factors from HC-402-05a cells. Based on immunofluorescence and
      reverse transcription-quantiative polymerase chain reaction analysis, the results
      indicated that hiPSCs have the capacity for effective chondrogenic
      differentiation, in particular cells differentiated in the HC-402-05a-conditioned
      medium, which present morphological features and markers that are characteristic
      of mature human chondrocytes. By contrast, cells differentiated in the presence
      of TGF-beta3 may demonstrate hypertrophic characteristics. Several genes [paired
      box 9, sex determining region Y-box (SOX) 5, SOX6, SOX9 and cartilage oligomeric
      matrix protein] were demonstrated to be good markers of early hiPSC chondrogenic
      differentiation: Insulin-like growth factor 1, Tenascin-C, and beta-catenin were
      less valuable. These observations provide valuable data on the use of hiPSCs in
      cartilage tissue regeneration.

PMID- 28447756
TI  - Matrine reduces the proliferation of A549 cells via the p53/p21/PCNA/eIF4E
      signaling pathway.
AB  - The aim of the present study was to investigate how matrine affects the
      proliferation of A549 human lung adenocarcinoma cells via the
      p53/p21/proliferating cell nuclear antigen (PCNA)/eukaryotic translation
      initiation factor 4E (eIF4E) signaling pathway. The effect of different
      concentrations of matrine on the proliferation of A549 cells was investigated
      using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
      The migration of A549 cells following exposure to varied concentrations of
      matrine was detected using a Transwell cell migration assay. The effect of 240
      mg/l matrine on the apoptotic rate of A549 cells was determined using flow
      cytometry. The change in the mRNA and protein expression levels of p53, p21, PCNA
      and eIF4E following exposure to matrine were detected using reverse transcription
      quantitative polymerase chain reaction and western blotting, respectively. The
      increase of matrine from 60-240 mg/l led to reduced cell migration and inhibition
      of A549 cell proliferation. The apoptotic rate of A549 cells when treated with
      240 mg/l matrine was significantly different when compared with the untreated
      control. The mRNA expression levels of p53 and p21 in the group treated with 240
      mg/l matrine were significantly higher compared with the control group. The mRNA
      expression levels of PCNA and eIF4E were significantly lower in the 240 mg/l
      matrine-treated group compared with the control. The protein expression levels of
      p53 and p21 were significantly higher in the 240 mg/l matrine group compared with
      the control group. Treatment with 240 mg/l matrine reduced the protein expression
      levels of PCNA and eIF4E. Matrine also reduced the migration ability of A549
      cells and inhibited their proliferation, which may be associated with the
      overexpression of p53 and p21, and the reduction of PCNA and eIF4E expression
      levels.

PMID- 28447757
TI  - Molecular mechanism of smurf2 in regulating the expression of SnoN in diabetic
      nephropathy.
AB  - The aim of the present study was to examine the regulatory mechanism underlying
      the depression in Ski-related novel protein N (SnoN) in diabetic nephrology (DN).
      NRK-52E cells, a rat primary renal tubular epithelial cell line, were cultured to
      clarify the effect of small mothers against decapentaplegic (Smad) ubiquitination
      regulatory factor 2 (smurf2) on SnoN in a low glucose environment in vitro. NRK
      52E cells and DM rats were injected with adenoviruses AD-smurf2 and AD-shsmurf2,
      respectively, and the protein expression profiles of SnoN, smurf2 and
      phosphorylated (p)-Smad2 were then detected. In addition, the protein levels of
      smurf2, p-Smad2 and SnoN were analyzed following treatment with transforming
      growth factor (TGF)-beta1 or TGF-beta1 inhibitor to validate the effect of the
      TGF-beta1/Smad signaling pathway. The effect of smurf2 on the degradation of SnoN
      by ubiquitination was found to be a key factor in DN, which was mediated by the
      TGF-beta1/Smad signaling pathway.

PMID- 28447758
TI  - Vitamin K2 promotes mesenchymal stem cell differentiation by inhibiting miR-133a
      expression.
AB  - Vitamin K2 has been demonstrated to promote the osteogenic differentiation of
      mesenchymal stem cells; however, the mechanisms underlying this effect remain
      unclear. As microRNA (miR)-133a has been identified as a negative regulator of
      osteogenic differentiation, the present study hypothesized that vitamin K2
      promoted osteogenesis by inhibiting miR-133a. Using human bone marrow stromal
      cells (hBMSCs) overexpressing miR-133a, or a control, the expression levels of
      osteogenesis-associated proteins, including runt-related transcription factor 2,
      alkaline phosphatase and osteocalcin, were analyzed. miR-133a significantly
      suppressed the osteogenic differentiation of hBMSCs. To determine the effect of
      vitamin K2 on miR-133a expression and osteogenesis, hBMSCs were treated with
      vitamin K2. Vitamin K2 inhibited miR-133a expression, which was accompanied by
      enhanced osteogenic differentiation. Furthermore, the expression levels of
      vitamin K epoxide reductase complex subunit 1, the key protein in gamma
      carboxylation, were downregulated by miR-133a overexpression and upregulated by
      vitamin K2 treatment, indicating a positive feedback on gamma-carboxylation. The
      results of the present study suggested that vitamin K2 targets miR-133a to
      regulate osteogenesis.

PMID- 28447759
TI  - miR-181a modulates proliferation, migration and autophagy in AGS gastric cancer
      cells and downregulates MTMR3.
AB  - MicroRNAs (miRs) have emerged as crucial regulators of tumorigenesis by
      regulating post-transcriptional gene expression. miR-181a was previously
      demonstrated to be overexpressed in human gastric cancer tissues and cell lines,
      whereas MTMR3 was underexpressed. The MTMR3 gene was identified as a direct
      target of miR-181a. However, its functional role in gastric cancer remains to be
      established. In the present study, miR-181a was demonstrated to inhibit MTMR3
      expression in AGS cells. Ectopic expression of miR-181a mimics or introduction of
      MTMR3 small interfering RNA resulted in an increase in cell proliferation, colony
      formation, migration, invasion, as well as suppression of apoptosis. Further
      investigation in the present study indicated that overexpression of miR-181a, or
      depletion of MTMR3, attenuated starvation-induced autophagy in AGS cells. In
      addition, inhibition of endogenous miR-181a led to stimulation of autophagic
      activity. Collectively, these data suggest that miR-181a is a novel regulator of
      gastric cancer progression and autophagy, and miR-181a modulation may be a
      potential strategy for the development of miRNA-based therapeutics for gastric
      cancer.

PMID- 28447760
TI  - Expression of mTOR/70S6K signaling pathway in pathological scar fibroblasts and
      the effects of resveratrol intervention.
AB  - The aim of the study was to examine the expression of mammalian target of
      rapamycin (mTOR)/70S6K signaling pathway in pathological scar fibroblasts and the
      effects of resveratrol (Res) intervention. The mTOR and 70S6K in pathological
      scar and normal skin fibroblasts were detected by immunofluorescence following
      treatment with different concentrations of Res. RT-PCR and western blot analysis
      were used to detect the expression of mTOR and 70S6K mRNA and protein,
      respectively. Immunofluorescence showed that the expression of 70S6K and mTOR was
      significantly enhanced in pathological scar fibroblasts, and mainly expressed in
      the nucleus, but not in normal skin fibroblasts. RT-PCR and western blot analysis
      showed that after different concentrations of Res treatments, the mTOR and 70S6K
      mRNA and protein expression significantly (P<0.05) decreased in a dose-dependent
      manner. In conclusion, the expression of mTOR/70S6K signaling pathway in
      pathological scar fibroblasts was significantly enhanced. Res can downregulate
      the expression of mTOR and 70S6K to achieve the inhibition of pathological scar
      fibroblast proliferation.

PMID- 28447761
TI  - miR-21 inhibitor suppresses cell proliferation and colony formation through
      regulating the PTEN/AKT pathway and improves paclitaxel sensitivity in cervical
      cancer cells.
AB  - The present study aimed to investigate the role and the molecular mechanisms
      underlying the effects of microRNA-21 (miR-21) on the proliferation, apoptosis
      and colony formation of cervical cancer cells, and to examine the role of miR-21
      in mediating the sensitivity of cervical cancer cells to paclitaxel (PTX).
      Reverse transcription-quantitative polymerase chain reaction was employed to
      determine the level of miR-21 in various cervical cancer and normal cervical
      cells. The results revealed that the expression levels of miR-21 in cervical
      cancer cells were markedly higher when compared with normal cervical cells.
      Subsequently, a miR-21 inhibitor or negative control (NC) was transfected into
      cervical cancer cells. Cell viability, colony formation and apoptosis were then
      analyzed using an MTT assay, crystal violet and Annexin V-fluorescein
      isothiocyanate/propidium iodide staining, respectively. The protein expression
      level of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), programmed cell
      death 4 (PDCD4), survivin, c-myc, phosphatase and tensin homolog (PTEN) and
      phosphorylated (p)-AKT were determined by western blot analysis. The sensitivity
      of cervical cancer cells to PTX (25, 50 and 100 ug/ml) was characterized using an
      MTT assay. The results demonstrated that the miR-21 inhibitor promoted apoptosis
      of cervical cancer cells and suppressed their proliferation and colony formation
      when compared with the NC. In addition, the expression levels of Bcl-2, survivin,
      c-myc and p-AKT were significantly downregulated in cells transfected with the
      miR-21 inhibitor, whilst the expression levels of Bax, PDCD4 and PTEN were
      significantly upregulated. Furthermore, the miR-21 inhibitor significantly
      enhanced the inhibition efficacy of PTX at a range of concentrations in cervical
      cancer cells. It was concluded that inhibition of miR-21 suppressed cell
      proliferation and colony formation through regulating the PTEN/AKT pathway, and
      improved PTX sensitivity in cervical cancer cells. The results of the present
      study may contribute to the development of miRNA-based cervical cancer therapy in
      the future.

PMID- 28447762
TI  - Inhibition of aldose reductase ameliorates ethanol-induced steatosis in HepG2
      cells.
AB  - Aldose reductase (AR) expression is increased in liver tissue of patients with
      ethanol-induced liver disease. However, the exact role of AR in the development
      of ethanol-induced liver disease has yet to be elucidated. The present study
      aimed to determine the effect of an AR inhibitor on ethanol-induced steatosis in
      HepG2 cells and to identify possible underlying molecular mechanisms. Steatosis
      was induced in HepG2 cells by stimulating cells with 100 mM absolute ethanol for
      48 h. Oil Red O staining was used to detect the lipid droplet accumulation in
      cells. Western blot analyses were used to determine protein expression levels and
      reverse transcription-quantitative polymerase chain reaction was used to analyze
      mRNA expression levels. The results showed that AR protein expression was
      elevated in HepG2 cells stimulated with ethanol. HepG2 cells exhibited marked
      improvement of ethanol-induced lipid accumulation following treatment with the AR
      inhibitor zopolrestat. Phosphorylation levels of 5' adenosine monophosphate
      activated protein kinase (AMPK) were markedly higher, whereas the mRNA expression
      levels of sterol-regulatory element-binding protein (SREBP)-1c and fatty acid
      synthase (FAS) were significantly lower in zopolrestat-treated and ethanol
      stimulated HepG2 cells compared with in untreated ethanol-stimulated HepG2 cells.
      In addition, zopolrestat inhibited the ethanol-induced expression of tumor
      necrosis factor (TNF)-alpha. These results suggested that zopolrestat attenuated
      ethanol-induced steatosis by activating AMPK and subsequently inhibiting the
      expression of SREBP-1c and FAS, and by suppressing the expression of TNF-alpha in
      HepG2 cells.

PMID- 28447763
TI  - Berberine protects against diet-induced obesity through regulating metabolic
      endotoxemia and gut hormone levels.
AB  - Systemic inflammation, which can be induced by metabolic endotoxemia, and
      corresponding high-fat diet-mediated metabolic disorders are associated with gut
      microbiota. In the present study reverse transcription-polymerase chain reaction,
      immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed
      to assess whether berberine can protect against diet-induced obesity, through
      modulating the gut microbiota and consequently improving metabolic endotoxemia
      and gastrointestinal hormone levels. Alterations in the gut microbiota induced by
      berberine resulted in a significant reduction in bacterial lipopolysaccharide
      levels in portal plasma. Levels of inflammatory and oxidative stress markers, as
      well as the mRNA expression levels of macrophage infiltration markers in visceral
      adipose tissue, were also reduced by berberine. Inhibition of the inflammatory
      response was associated with a reduction in intestinal permeability and an
      increase in the expression of tight junction proteins. In addition, berberine was
      reported to restore aberrant levels of gut hormones in the portal plasma, such as
      glucagon-like peptide-1 and -2, peptide YY, glucose-dependent insulinotropic
      polypeptide and pancreatic polypeptide. The present findings indicated that
      berberine, through modulating gut microbiota, restored the gut barrier, reduced
      metabolic endotoxemia and systemic inflammation, and improved gut peptide levels
      in high-fat diet-fed rats. The present study suggests that berberine may be an
      effective therapeutic strategy for the treatment of obesity and insulin
      resistance.

PMID- 28447764
TI  - Sevoflurane anesthesia in pregnant rats negatively affects nerve function in
      offspring potentially via inhibition of the Wnt/beta-catenin pathway.
AB  - Due to the rapid development of medical technology used to perform intrauterine
      procedures during pregnancy, the number of patients receiving fetal surgery under
      general anesthesia is increasing. The aim of the present study was to determine
      the effects of anesthetics on the offspring of rats, and to identify the
      potential mechanisms underlying these effects. On day 14 of pregnancy, Sprague
      Dawley rats were equally divided into the following 3 groups (n=9): Control group
      (n=3), 3% sevoflurane group (n=3) and 4% sevoflurane group (n=3). Following birth
      of the offspring, the juvenile rats were assessed using an open-field test,
      Morris water maze and a continuous passive avoidance test on different days to
      determine their learning abilities and memory. Western blot and reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were used
      to examine the expression of multiple critical factors associated with the
      proliferation and apoptosis of nerve cells, including Ki67, nestin, B cell
      leukemia/lymphoma 2 (Bcl-2), BCL2 associated X (Bax) and caspase-3. Additionally,
      the level of adenosine triphosphate production among the 3 groups were compared.
      Furthermore, expression alterations in of glycogen synthase kinase-3beta (GSK
      3beta) and beta-catenin were examined. The Morris water maze experiment revealed
      that an increased concentration of sevoflurane exposure significantly reduced the
      learning and memory abilities of the juvenile rats when compared with controls.
      In addition, western blotting and RT-qPCR analyses determined that the protein
      and mRNA expression levels of Bax, caspase-3 and GSK-3beta were significantly
      increased relative to the controls. By contrast, the expression levels of nestin,
      Ki-67, Bcl-2 and beta-catenin were significantly reduced. The results of the
      present study suggest that exposure of pregnant mice to sevoflurane anesthesia
      demonstrates a negative effect on the learning and memory abilities of their
      offspring, and the Wnt/beta-catenin signaling pathway may be involved in this
      process.

PMID- 28447765
TI  - Plasma microRNA-451 as a novel hemolytic marker for beta0-thalassemia/HbE
      disease.
AB  - In Southeast Asia, particularly in Thailand, beta0-thalassemia/hemoglobin E (HbE)
      disease is a common hereditary hematological disease. It is associated with
      pathophysiological processes, such as the intramedullary destruction of immature
      erythroid cells and peripheral hemolysis of mature red blood cells. MicroRNA
      (miR) sequences, which are short non-coding RNA that regulate gene expression in
      a suppressive manner, serve a crucial role in human erythropoiesis. In the
      present study, the plasma levels of the erythroid-expressed miRNAs, miR-451 and
      miR-155, were analyzed in 23 patients with beta0-thalassemia/HbE and 16 control
      subjects. Reverse transcription-quantitative polymerase chain reaction analysis
      revealed significantly higher levels of plasma miR-451 and miR-155 in beta0
      thalassemia/HbE patients when compared to the control subjects. Notably, among
      the beta0-thalassemia/HbE patients, a significant increase in miR-451 levels was
      detected in severe cases when compared with mild cases. The levels of plasma miR
      451 correlated with reticulocyte and platelet counts. The results suggest that
      increased plasma miR-451 levels may be associated with the degree of hemolysis
      and accelerated erythropoiesis in beta0-thalassemia/HbE patients. In conclusion,
      miR-451 may represent a relevant biomarker for pathological erythropoiesis
      associated with beta0-thalassemia/HbE.

PMID- 28447766
TI  - Supervised dosing with a long-acting opioid medication in the management of
      opioid dependence.
AB  - BACKGROUND: Opioid dependence (OD) is an increasing clinical and public health
      problem worldwide. International guidelines recommend opioid substitution
      treatment (OST), such as methadone and buprenorphine, as first-line medication
      treatment for OD. A negative aspect of OST is that the medication used can be
      diverted both through sale on the black market, and the unsanctioned use of
      medications. Daily supervised administration of medications used in OST has the
      advantage of reducing the risk of diversion, and may promote therapeutic
      engagement, potentially enhancing the psychosocial aspect of OST, but costs more
      and is more restrictive on the client than dispensing for off-site consumption.
      OBJECTIVES: The objective of this systematic review is to compare the
      effectiveness of OST with supervised dosing relative to dispensing of medication
      for off-site consumption. SEARCH METHODS: We searched in Cochrane Drugs and
      Alcohol Group Specialised Register and Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science from inception up to
      April 2016. Ongoing and unpublished studies were searched via ClinicalTrials.gov
      (www.clinicaltrials.gov) and World Health Organization (WHO) International
      Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/).All
      searches included non-English language literature. We handsearched references on
      topic-related systematic reviews. SELECTION CRITERIA: Randomised controlled
      trials (RCTs), controlled clinical trials (CCTs), and prospective controlled
      cohort studies, involving people who are receiving OST (methadone, buprenorphine)
      and comparing supervised dosing with dispensing of medication to be consumed away
      from the dispensing point, usually without supervision. DATA COLLECTION AND
      ANALYSIS: We used the standard methodological procedures expected by Cochrane.
      MAIN RESULTS: Six studies (four RCTs and two prospective observational cohort
      studies), involving 7999 participants comparing supervised OST treatment with
      unsupervised treatment, met the inclusion criteria. The risk of bias was
      generally moderate across trials, but the results reported on outcomes that we
      planned to consider were limited. Overall, we judged the quality of the evidence
      from very low to low for all the outcomes.We found no difference in retention at
      any duration with supervised compared to unsupervised dosing (RR 0.99, 95% CI
      0.88 to 1.12, 716 participants, four trials, low-quality evidence) or in
      retention in the shortest follow-up period, three months (RR 0.94; 95% CI 0.84 to
      1.05; 472 participants, three trials, low-quality evidence). Additional data at
      12 months from one observational study found no difference in retention between
      groups (RR 0.94, 95% CI 0.77 to 1.14; n = 300).There was no difference in
      abstinence at the end of treatment (self-reported drug use) (67% versus 60%, P =
      0.33, 293 participants, one trial, very low-quality evidence); and in diversion
      of medication (5% versus 2%, 293 participants, one trial, very low-quality
      evidence).Regarding our secondary outcomes, we did not found a difference in the
      incidence of adverse effects in the supervised compared to unsupervised control
      group (RR 0.63; 96% CI 0.10 to 3.86; 363 participants, two trials, very low
      quality evidence). Data on severity of dependence were very limited (244
      participants, one trial) and showed no difference between the two approaches.
      Data on deaths were reported in two studies. One trial reported two deaths in the
      supervised group (low-quality evidence), while in the cohort study all-cause
      mortality was found lower in regular supervision group (crude mortality rate 0.60
      versus 0.81 per 100 person-years), although after adjustment insufficient
      evidence existed to suggest that regular supervision was protective (mortality
      rate ratio = 1.23, 95% CI = 0.67 to 2.27).No studies reported pain symptoms, drug
      craving, aberrant opioid-related behaviours, days of unsanctioned opioid use and
      overdose. AUTHORS' CONCLUSIONS: Take-home medication strategies are attractive to
      treatment services due to lower costs, and place less restrictions on clients,
      but it is unknown whether they may be associated with increased risk of diversion
      and unsanctioned use of medication. There is uncertainty about the effects of
      supervised dosing compared with unsupervised medication due to the low and very
      low quality of the evidence for the primary outcomes of interest for this review.
      Data on defined secondary outcomes were similarly limited. More research
      comparing supervised and take-home medication strategies is needed to support
      decisions on the relative effectiveness of these strategies. The trials should be
      designed and conducted with high quality and over a longer follow-up period to
      support comparison of strategies at different stages of treatment. In particular,
      there is a need for studies assessing in more detail the risk of diversion and
      safety outcomes of using supervised OST to manage opioid dependence.

PMID- 28447767
TI  - Biopsy versus resection for the management of low-grade gliomas.
AB  - BACKGROUND: This is an updated version of the original Cochrane review published
      in 2013, Issue 4.Low-grade gliomas (LGG) constitute a class of slow-growing
      primary brain neoplasms. Patients with clinically and radiographically suspected
      LGG have two initial surgical options, biopsy or resection. Biopsy can provide a
      histological diagnosis with minimal risk but does not offer a direct treatment.
      Resection may have additional benefits such as increasing survival and delaying
      recurrence, but is associated with a higher risk for surgical morbidity. There
      remains controversy about the role of biopsy versus resection and the relative
      clinical outcomes for the management of LGG. OBJECTIVES: To assess the clinical
      effectiveness of biopsy compared to surgical resection in patients with a new
      lesion suspected to be a LGG. SEARCH METHODS: The following electronic databases
      were searched in 2012 for the first version of the review: Cochrane Central
      Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to
      November week 3 2012), Embase (1980 to Week 46 2012). For this updated version,
      the following electronic databases were searched: Cochrane Central Register of
      Controlled Trials (CENTRAL) (2016, Issue 5), MEDLINE (Nov 2012 to June week 3
      2016), Embase (Nov 2012 to 2016 week 26). All relevant articles were identified
      on PubMed and by using the 'related articles' feature. We also searched
      unpublished and grey literature including ISRCTN-metaRegister of Controled
      Trials, Physicians Data Query and ClinicalTrials.gov for ongoing trials.
      SELECTION CRITERIA: We planned to include patients of any age with a suspected
      intracranial LGG receiving biopsy or resection within a randomized clinical trial
      (RCT) or controlled clinical trial (CCT). Patients with prior resections,
      radiation therapy, or chemotherapy for LGG were excluded. Outcome measures
      included overall survival (OS), progression-free survival (PFS), functionally
      independent survival (FIS), adverse events, symptom control, and quality of life
      (QoL). DATA COLLECTION AND ANALYSIS: A total of 1375 updated citations were
      searched and critically analyzed for relevance. This was undertaken independently
      by two review authors. The original electronic database searches yielded a total
      of 2764 citations. In total, 4139 citations have been critically analyzed for
      this updated review. MAIN RESULTS: No new RCTs of biopsy or resection for LGG
      were identified. No additional ineligible non-randomized studies (NRS) were
      included in this updated review. Twenty other ineligible studies were previously
      retrieved for further analysis despite not meeting the pre-specified criteria.
      Ten studies were retrospective or were literature reviews. Three studies were
      prospective, however they were limited to tumor recurrence and volumetric
      analysis and extent of resection. One study was a population-based parallel
      cohort in Norway, but not an RCT. Four studies were RCTs, however patients were
      randomized with respect to varying radiotherapy regimens to assess timing and
      dose of radiation. One RCT was on high-grade gliomas (HGGs) and not LGG. Finally,
      one RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for
      surgical resection. AUTHORS' CONCLUSIONS: Since the last version of this review,
      no new studies have been identified for inclusion and currently there are no RCTs
      or CCTs available on which to base definitive clinical decisions. Therefore,
      physicians must approach each case individually and weigh the risks and benefits
      of each intervention until further evidence is available. Some retrospective
      studies and non-randomized prospective studies do seem to suggest improved OS and
      seizure control correlating to higher extent of resection. Future research could
      focus on RCTs to determine outcomes benefits for biopsy versus resection.

PMID- 28447768
TI  - Bio-Inspired Bright Structurally Colored Colloidal Amorphous Array Enhanced by
      Controlling Thickness and Black Background.
AB  - Inspired by Steller's jay, which displays angle-independent structural colors,
      angle-independent structurally colored materials are created, which are composed
      of amorphous arrays of submicrometer-sized fine spherical silica colloidal
      particles. When the colloidal amorphous arrays are thick, they do not appear
      colorful but almost white. However, the saturation of the structural color can be
      increased by (i) appropriately controlling the thickness of the array and (ii)
      placing the black background substrate. This is similar in the case of the blue
      feather of Steller's jay. Based on the knowledge gained through the biomimicry of
      structural colored materials, colloidal amorphous arrays on the surface of a
      black particle as the core particle are also prepared as colorful photonic
      pigments. Moreover, a structural color on-off system is successfully built by
      controlling the background brightness of the colloidal amorphous arrays.

PMID- 28447769
TI  - Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

PMID- 28447770
TI  - Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

PMID- 28447771
TI  - Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

PMID- 28447773
TI  - Hypothermia after In-Hospital Cardiac Arrest in Children.

PMID- 28447772
TI  - Hypothermia after In-Hospital Cardiac Arrest in Children.

PMID- 28447774
TI  - Nitrogen and Phosphorus Codoped Mesoporous Carbon Derived from Polypyrrole as
      Superior Metal-Free Electrocatalyst toward the Oxygen Reduction Reaction.
AB  - To replace high-cost platinum group metal (PGM) electrocatalysts for oxygen
      reduction reaction (ORR) that is the crucial cathode reaction in fuel cell
      technology and metal-air battery, the development of low-cost and high-efficiency
      non-PGM catalysts for ORR has attracted much attention during the past decades.
      As one of the promising candidates, N-doped carbon is highly desirable for its
      strong designability and outstanding catalytic activity and stability. In this
      work, a facile and rational strategy is demonstrated for preparation of N,P
      codoped mesoporous carbon (N,P-MC) for ORR by the direct pyrolysis treatment of
      polypyrrole with phytic acid as P-dopant and polystyrene sphere as template. The
      resultant N,P-MC exhibits a mesoporous structure with the optimized ORR active
      sites originating from the N,P-codoping. Owing to these features, N,P-MC exhibits
      excellent ORR activity, remarkable electrochemical stability, and superior
      methanol tolerance, comparable or even better than that of commercial Pt/C
      catalyst. The origin of enhanced ORR performance can be attributed to both the
      increased active sites and the mesoporous structure, which is expected to guide
      the future preparation of more capable carbon-based electrocatalysts for oxygen
      reduction and other electrocatalytic application.

PMID- 28447775
TI  - Preparation, Characterization, and Electrochromic Properties of Nanocellulose
      Based Polyaniline Nanocomposite Films.
AB  - On the basis of nanocellulose obtained by acidic swelling and ultrasonication,
      rodlike nanocellulose/polyaniline nanocomposites with a core-shell structure have
      been prepared via in situ polymerization. Compared to pure polyaniline, the
      nanocomposites show superior film-forming properties, and the prepared
      nanocomposite films demonstrate excellent electrochemical and electrochromic
      properties in electrolyte solution. Nanocomposite films, especially the one
      prepared with 40% polyaniline coated nanocomposite, exhibited faster response
      time (1.5 s for bleaching and 1.0 s for coloring), higher optical contrast
      (62.9%), higher coloration efficiency (206.2 cm2/C), and more remarkable
      switching stability (over 500 cycles). These novel nanocellulose-based nanorod
      network films are promising novel electrochromic materials with excellent
      properties.

PMID- 28447776
TI  - Investigation of the Changes in Electronic Properties of Nickel Oxide (NiOx) Due
      to UV/Ozone Treatment.
AB  - Drastic reduction in nickel oxide (NiOx) film resistivity and ionization
      potential is observed when subjected to ultraviolet (UV)/ozone (O3) treatment. X
      ray photoemission spectroscopy suggests that UV/O3 treatment changes the film
      stoichiometry by introducing Ni vacancy defects. Oxygen-rich NiOx having Ni
      vacancy defects behaves as a p-type semiconductor. Therefore, in this work, a
      simple and effective technique to introduce doping in NiOx is shown. Angle
      resolved XPS reveals that the effect of UV/O3 treatment does not only alter the
      film surface property but also introduces oxygen-rich stoichiometry throughout
      the depth of the film. Finally, simple metal/interlayer/semiconductor (MIS)
      contacts are fabricated on p-type Si using NiOx as the interlayer and different
      metals. Significant barrier height reduction is observed with respect to the
      control sample following UV/O3 treatment, which is in agreement with the observed
      reduction in film resistivity. From an energy band diagram point of view, the
      introduction of the UV/O3 treatment changes the defect state distribution,
      resulting in a change in the pinning of the Fermi level. Therefore, this work
      also shows that the Fermi level pinning property of NiOx can be controlled using
      UV/O3 treatment.

PMID- 28447777
TI  - Phosphorus-Rich CuP2 Embedded in Carbon Matrix as a High-Performance Anode for
      Lithium-Ion Batteries.
AB  - Phosphorus-rich CuP2 and its carbon composites have been investigated as an anode
      material for lithium-ion batteries. Through a facile, low-cost mechanochemical
      reaction, microsized composites composed of active CuP2 particles uniformly
      embedded in the carbon matrix have been successfully synthesized. Combined
      structural and electrochemical characterizations show that phosphorus-rich CuP2
      undergoes irreversible reaction with lithium, giving metal-rich Cu3P and
      amorphous phosphorus at the end of the first cycle. Both Cu3P and phosphorus are
      reversibly formed in subsequent cycles, contributing to a high reversible
      capacity of >1000 mA h g-1. By controlling the carbon content, the
      electrochemical reversibility and stability of CuP2 are greatly improved. The
      carbon composite demonstrates a remarkable lithium-storage capability in terms of
      a stable capacity of >720 mA h g-1 over 100 cycles at 200 mA g-1, a high initial
      Coulombic efficiency of ~83%, and a good rate capability with a capacity of >637
      mA h g-1 at 1.6 A g-1. The performance improvement is mainly associated with the
      formation of the conductive carbon network that offers high conductivity and fast
      reaction kinetics, as well as enhanced structural stability of CuP2 anode.

PMID- 28447778
TI  - As Precious as Platinum: Iron Nitride for Electrocatalytic Oxidation of Liquid
      Ammonia.
AB  - The electrolysis of ammonia (NH3), a potential carrier for hydrogen fuel, has
      only been studied in detail in systems employing expensive, noble metal anodes
      such as platinum, ruthenium, and iridium. For NH3 to serve as a practical
      hydrogen storage medium, the electrolysis process must be energy efficient,
      scalable, and inexpensive. Clearly, alternatives to precious metals would greatly
      reduce costs if the performance of less expensive, more abundant metals rivaled
      those of their expensive counterparts. In this regard, no metal is less expensive
      than iron. Iron exhibits complex anodic behavior in liquid ammonia (NH3(l)), with
      a high sensitivity to trace amounts of dissolved water, and a tendency to
      corrosively dissolve with appropriate applied bias. However, with sufficient
      applied overpotential in distilled NH3(l), an iron nitride film forms in situ
      that is resistant to dissolution. On this in situ-modified surface, dinitrogen
      evolution out-performs anodic dissolution with an efficiency of over 95%.
      Amazingly, the onset potential for dinitrogen evolution in NH3(l) on this in situ
      modified iron surface is almost identical to what is measured on a platinum
      electrode.

PMID- 28447779
TI  - Performance and Mechanism of Piezo-Catalytic Degradation of 4-Chlorophenol:
      Finding of Effective Piezo-Dechlorination.
AB  - Piezo-catalysis was first used to degrade a nondye pollutant, 4-chlorophenol (4
      CP). In this process, hydrothermally synthesized tetragonal BaTiO3
      nano/micrometer-sized particles were used as the piezo-catalyst, and the
      ultrasonic irradiation with low frequency was selected as the vibration energy to
      cause the deformation of tetragonal BaTiO3. It was found that the piezoelectric
      potential from the deformation could not only successfully degrade 4-chlorophenol
      but also effectively dechlorinate it at the same time, and five kinds of
      dechlorinated intermediates, hydroquinone, benzoquinone, phenol, cyclohexanone,
      and cyclohexanol, were determined. This is the first sample of piezo
      dechlorination. Although various active species, including h+, e-, *H, *OH, *O2-,
      1O2, and H2O2, were generated in the piezoelectric process, it was confirmed by
      ESR, scavenger studies, and LC-MS that the degradation and dechlorination were
      mainly attributed to *OH radicals. These *OH radicals were chiefly derived from
      the electron reduction of O2, partly from the hole oxidation of H2O. These
      results indicated that the piezo-catalysis was an emerging and effective advanced
      oxidation technology for degradation and dechlorination of organic pollutants.

PMID- 28447780
TI  - High and Selective Carbon Dioxide Capture in Nitrogen-Containing Aerogels via
      Synergistic Effects of Electrostatic In-Plane and Dispersive pi-pi-Stacking
      Interactions.
AB  - A new strategy for CO2 capture is reported based on the synergistic effect of
      electrostatic in-plane and dispersive pi-pi-stacking interactions of amide and
      indole with CO2. Density functional theory illustrated that the amide group can
      have an increased ability to capture CO2 molecules that were just desorbed from
      an adjacent indole unit. We used this strategy to fabricate a microporous aerogel
      that exhibited a superior CO2 capture performance in both dry and wet conditions.
      The proposed synergistic effect is expected to be a new rationale for the design
      of CO2 capture materials.

PMID- 28447781
TI  - Artemisinin Protects Retinal Neuronal Cells against Oxidative Stress and Restores
      Rat Retinal Physiological Function from Light Exposed Damage.
AB  - Oxidative stress plays a key role in the pathogenesis of age-related macular
      degeneration (AMD), a leading cause of severe visual loss and blindness in the
      aging population which lacks any effective treatments currently. In this study,
      artemisinin, a well-known antimalarial drug was found to suppress hydrogen
      peroxide (H2O2)-induced cell death in retinal neuronal RGC-5 cells. Artemisinin,
      in the therapeutically relevant dosage, concentration-dependently attenuated the
      accumulation of intracellular reactive oxygen species (ROS), increased
      mitochondrial membrane potential and decreased cell apoptosis in RGC-5 cells
      induced by H2O2. Western blot analysis showed that artemisinin upregulated the
      phosphorylation of p38 and extracellular signal-regulated kinases1/2 (ERK1/2) and
      reversed the inhibitory effect of H2O2 on the phosphorylation of these two
      kinases. Moreover, protective effect of artemisinin was blocked by the p38 kinase
      inhibitor PD169316 or ERK1/2 kinase pathway inhibitor PD98059, respectively. In
      contrast, c-Jun N-terminal kinase inhibitor and rapamycin had no effect in the
      protective effect of artemisinin. Taken together, these results demonstrated that
      artemisinin promoted the survival of RGC-5 cells from H2O2 toxicity via the
      activation of the p38 and ERK1/2 pathways. Interestingly, intravitreous injection
      of artimisinin, concentration-dependently reversed light exposed-damage (a dry
      AMD animal model) of rat retinal physiological function detected by flash
      electroretinogram. These results indicate that artemisinin can protect retinal
      neuronal functions from H2O2-induced damage in vitro and in vivo and suggest the
      potential application of artemisinin as a new drug in the treatment of retinal
      disorders like AMD.

PMID- 28447782
TI  - Does Waterborne Exposure Explain Effects Caused by Neonicotinoid-Contaminated
      Plant Material in Aquatic Systems?
AB  - Neonicotinoids are increasingly applied on trees as protection measure against
      insect pests. Consequently, neonicotinoids are inevitably transferred into
      aquatic environments either via spray drift or surface runoff or (due to
      neonicotinoids' systemic nature) via senescent leaves. There particularly leaf
      shredding invertebrates may be exposed to neonicotinoids through both the water
      phase and the consumption of contaminated leaves. In 7 day bioassays (n = 30), we
      examined ecotoxicological differences between these two exposure scenarios for an
      amphipod and an insect nymph with their feeding rate as the response variable.
      Organisms either experienced waterborne neonicotinoid (i.e., imidacloprid,
      thiacloprid, and acetamiprid) exposure only or a combined exposure (waterborne
      and dietary) through both the consumption of contaminated leaves and
      neonicotinoids leaching from leaves into water. The amphipod (7 day EC50s from
      0.3 to 8.4 MUg/L) was more sensitive than the insect nymph (7 day EC50s from 7.0
      to 19.4 MUg/L). Moreover, for both species, concentration-response models derived
      from water concentrations indicated higher effects under the combined exposure.
      Together with the observed inability of shredders to avoid neonicotinoid
      contaminated leaves, our results emphasize the relevance of dietary exposure
      (e.g., via leaves) for systemic insecticides. Thus, it would be prudent to
      consider dietary exposure during the registration of systemic insecticides to
      safeguard ecosystem integrity.

PMID- 28447783
TI  - Real-Time Detection Reveals Responsive Cotranscriptional Formation of Persistent
      Intramolecular DNA and Intermolecular DNA:RNA Hybrid G-Quadruplexes Stabilized by
      R-Loop.
AB  - G-quadruplex (GQ) structures are implicated in important physiological and
      pathological processes. Millions of GQ-forming motifs are enriched near
      transcription start sites (TSSs) of animal genes. Transcription can induce the
      formation of GQs, which in turn regulate transcription. The kinetics of the
      formation and persistence of GQs in transcription is crucial for the role they
      play but has not yet been explored. We established a method based on the
      fluorescence resonance energy transfer (FRET) technique to monitor in real-time
      the cotranscriptional formation and post-transcriptional persistence of GQs in
      DNA. Using a T7 transcription model, we demonstrate that a representative
      intramolecular DNA GQ and DNA:RNA hybrid GQ promptly form in proportion to
      transcription activity and, once formed, are maintained for hours or longer at
      physiological temperature even after transcription is stopped. Both their
      formation and persistence strongly depend on R-loop, a DNA:RNA hybrid duplex
      formed during transcription. Enzymatic removal of R-loop dramatically slows their
      formation and accelerates their unfolding. These results suggest that a
      transcription event is promptly read-out by GQ-forming motifs and the GQ formed
      can either perform regulation in fast response to transcription and/or memorized
      in DNA to mediate time-delayed regulation under the control of RNA metabolism and
      GQ-resolving activity. Alternatively, GQs need to be timely resolved to warrant
      success of translocating activities such as replication. The kinetic
      characteristics of GQs and its connection with the R-loop may have implications
      in transcription regulation, signal transduction, G-quadruplex processing, and
      genome stability.

PMID- 28447784
TI  - DFT-Based Comparative Study about the Influence of Fluorine and Hydroxyl Anions
      on Opto-Electric Properties of Borate Crystals: Choice for Better Anion.
AB  - Replacing hydroxyl anions OH- by fluorine anions F- in borates can cause the blue
      shift of the UV cutoff edge and also exhibits apparent differences in nonlinear
      optical (NLO) properties. To clarify the intrinsic difference between OH- anions
      and F- anions, several typical borates with different types of cations (p-cations
      with lone-pair electrons, trivalent rare-earth, and alkaline earth metals) have
      been studied. The theoretical studies reveal that the blue shift in the band gap
      of borates with fluorine as compared to those with hydroxyl can be assumed to be
      the result of weaker interaction of the cation-fluoride (La/Bi/B-F) bonds
      compared to that of the cation-oxygen and hydroxyl bonds. NLO properties are
      found to have the order of BiB2O4F > BiB2O4(OH)> LaB2O4F ~ LaB2O4(OH). The large
      difference can be attributed mainly to the stereochemical activity of the lone
      pair (SCALP) effect of the Bi cations and the special BO3F with strong anisotropy
      as compared to the BO4 group. The energy spanning of F-2p orbitals is more
      extended in BiB2O4F as compared to LaB2O4F, Sr3B6O11F2, and Ba3B6O11F2 due to the
      bonding of Bi/B-F, which indicates F-2p orbitals have more chance to overlap with
      surrounding atoms and enhance the polarizability in all systems. Moreover, the
      degree of SCALP of the Bi cations is apparently activated by the introduction of
      the F- anions, which causes an obvious enhancement in NLO properties in bismuth
      borates with F-. These investigations will help us to classify the solid-state
      chemistry of F- and OH- anions in borate systems with different types of metal
      cations.

PMID- 28447785
TI  - Graphene Microcapsule Arrays for Combinatorial Electron Microscopy and
      Spectroscopy in Liquids.
AB  - Atomic-scale thickness, molecular impermeability, low atomic number, and
      mechanical strength make graphene an ideal electron-transparent membrane for
      material characterization in liquids and gases with scanning electron microscopy
      and spectroscopy. Here, we present a novel sample platform made of an array of
      thousands of identical isolated graphene-capped microchannels with high aspect
      ratio. A combination of a global wide field of view with high resolution local
      imaging of the array allows for high throughput in situ studies as well as for
      combinatorial screening of solutions, liquid interfaces, and immersed samples. We
      demonstrate the capabilities of this platform by studying a pure water sample in
      comparison with alkali halide solutions, a model electrochemical plating process,
      and beam-induced crystal growth in liquid electrolyte. Spectroscopic
      characterization of liquid interfaces and immersed objects with Auger and X-ray
      fluorescence analysis through the graphene membrane are also demonstrated.

PMID- 28447786
TI  - 3D MAS NMR Experiment Utilizing Through-Space 15N-15N Correlations.
AB  - We demonstrate a novel 3D NNC magic angle spinning NMR experiment that generates
      15N-15N internuclear contacts in protein systems using an optimized 15N-15N
      proton assisted recoupling (PAR) mixing period and a 13C dimension for improved
      resolution. The optimized PAR condition permits the acquisition of high signal-to
      noise 3D data that enables backbone chemical shift assignments using a strategy
      that is complementary to current schemes. The spectra can also provide distance
      constraints. The utility of the experiment is demonstrated on an M0Abeta1-42
      fibril sample that yields high-quality data that is readily assigned and
      interpreted. The 3D NNC experiment therefore provides a powerful platform for
      solid-state protein studies and is broadly applicable to a variety of systems and
      experimental conditions.

PMID- 28447787
TI  - Designing Dual Emissions via Co-doping or Physical Mixing of Individually Doped
      ZnO and Their Implications in Optical Thermometry.
AB  - Here, we report on the novel design of dual emission via defect state engineering
      in codoped oxide microstructures and its implication in fluorescence intensity
      ratio (FIR) based optical temperature sensing. Eu- and Er-co-doped ZnO (EuEr:ZnO)
      microrods prepared by hydrothermal method. The emission peaks corresponding to
      Eu3+ and Er3+ are observed suggesting dual emission from codoped ZnO.
      Interestingly, Er3+ peak intensity decreases and that of Eu3+ increases with
      increase of temperature as is the case of individual doped cases and dual
      emission is also achieved via phyical mixing of the individual doped ZnO. The
      opposite trend is due to the electron transfer from the defect levels of host ZnO
      to Eu3+ and not to Er3+. Overall, our results pave the way in designing dual
      emission that can be exploited in FIR based temperature sensing. As an example,
      we probe temperature dependency of congo-red and polyvinyle alcohol (PVA)
      composite using EuEr:ZnO as optical probe for temperature sensing.

PMID- 28447788
TI  - A Wide-Bandgap Donor Polymer for Highly Efficient Non-fullerene Organic Solar
      Cells with a Small Voltage Loss.
AB  - To achieve efficient non-fullerene organic solar cells, it is important to reduce
      the voltage loss from the optical bandgap to the open-circuit voltage of the
      cell. Here we report a highly efficient non-fullerene organic solar cell with a
      high open-circuit voltage of 1.08 V and a small voltage loss of 0.55 V. The high
      performance was enabled by a novel wide-bandgap (2.05 eV) donor polymer paired
      with a narrow-bandgap (1.63 eV) small-molecular acceptor (SMA). Our morphology
      characterizations show that both the polymer and the SMA can maintain high
      crystallinity in the blend film, resulting in crystalline and small domains. As a
      result, our non-fullerene organic solar cells realize an efficiency of 11.6%,
      which is the best performance for a non-fullerene organic solar cell with such a
      small voltage loss.

PMID- 28447790
TI  - Improvement of Photovoltaic Performance of Colloidal Quantum Dot Solar Cells
      Using Organic Small Molecule as Hole-Selective Layer.
AB  - A novel organic small molecule bis-triphenylamine with spiro(fluorene-9,9'
      xanthene) as the conjugated system, named BTPA-4, is successfully synthesized and
      employed as the hole-selective layer (HSL) in colloidal quantum dots solar cells
      (CQDSCs). The introduction of BTPA-4 layer can significantly prolong effective
      carrier lifetime (taueff), increase charge recombination resistance (Rrec), and
      thus diminish the interfacial charge recombination at the PbS-QDs/Au electrode
      interface. The effect of BTPA-4 as HSL in the device performance is especially
      significant for the open-circuit voltage (Voc) and power conversion efficiency
      (PCE), with a ~ 10% and 15% enhancement respectively, comparing with those of
      device without the HSL. Furthermore, the PbS CQDSCs with BTPA-4 possessed a
      noticeably stable property for over 100 days of storage under ambient atmosphere.

PMID- 28447789
TI  - Exploring the Role of N6-Substituents in Potent Dual Acting 5'-C
      Ethyltetrazolyladenosine Derivatives: Synthesis, Binding, Functional Assays, and
      Antinociceptive Effects in Mice ?.
AB  - Structural determinants of affinity of N6-substituted-5'-C-(ethyltetrazol-2
      yl)adenosine and 2-chloroadenosine derivatives at adenosine receptor (AR)
      subtypes were studied with binding and molecular modeling. Small N6-cycloalkyl
      and 3-halobenzyl groups furnished potent dual acting A1AR agonists and A3AR
      antagonists. 4 was the most potent dual acting human (h) A1AR agonist (Ki = 0.45
      nM) and A3AR antagonist (Ki = 0.31 nM) and highly selective versus A2A; 11 and 26
      were most potent at both h and rat (r) A3AR. All N6-substituted-5'-C
      (ethyltetrazol-2-yl)adenosine derivatives proved to be antagonists at hA3AR but
      agonists at the rA3AR. Analgesia of 11, 22, and 26 was evaluated in the mouse
      formalin test (A3AR antagonist blocked and A3AR agonist strongly potentiated). N6
      Methyl-5'-C-(ethyltetrazol-2-yl)adenosine (22) was most potent, inhibiting both
      phases, as observed combining A1AR and A3AR agonists. This study demonstrated for
      the first time the advantages of a single molecule activating two AR pathways
      both leading to benefit in this acute pain model.

PMID- 28447791
TI  - Discovery of a Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2
      (SGLT2) Inhibitor (HSK0935) for the Treatment of Type 2 Diabetes.
AB  - A new class of potent and highly selective SGLT2 inhibitors is disclosed.
      Compound 31 (HSK0935) demonstrated excellent hSGLT2 inhibition of 1.3 nM and a
      high hSGLT1/hSGLT2 selectivity of 843-fold. It showed robust urinary glucose
      excretion in Sprague-Dawley (SD) rats and affected more urinary glucose excretion
      in Rhesus monkeys. Finally, an efficient synthetic route has been developed
      featuring a ring-closing cascade reaction to incorporate a double ketal 1-methoxy
      6,8-dioxabicyclo[3.2.1]octane ring system.

PMID- 28447792
TI  - "Liquid Crystalline Nanoparticles": Rationally Designed Vehicle To Improve
      Stability and Therapeutic Efficacy of Insulin Following Oral Administration.
AB  - In the present article we investigate the feasibility of liquid crystalline
      nanoparticles (LCNPs) to improve the stability and therapeutic efficacy of
      insulin following oral administration. Compatibility studies of different
      formulation ingredients with insulin and extensive optimization of different
      process variables resulted into the formation of LCNPs with particle size of
      245.50 +/- 6.36 nm, PDI of 0.220 +/- 0.042, and zeta potential of -18.30 +/- 1.27
      mV with an entrapment efficiency of 44.17 +/- 1.47%. Mannitol (5% w/v) was
      identified as a suitable cryoprotectant to produce freeze-dried LCNPs without
      affecting their critical quality attributes. LCNPs demonstrated excellent
      stability in simulated biological fluids by simultaneously retaining the chemical
      and conformational stability of the insulin entrapped within the LCNPs. A
      sustained release of insulin was observed for up to 24 h in PBS (pH 7.4).
      Developed LCNPs demonstrated remarkably higher Caco-2 cell uptake in comparison
      with free insulin-FITC and more than double the cumulative hypoglycemia in
      comparison with subcutaneously administered insulin solution in diabetic rats.
      Data in hand suggest that the proposed formulation strategy can be exploited for
      improving the therapeutic efficacy of biomacromolecules like insulin.

PMID- 28447794
TI  - Palladium-Catalyzed Asymmetric Benzylic Substitution of Secondary Benzyl
      Carbonates with Nitrogen and Oxygen Nucleophiles.
AB  - A Pd/(R)-BINAP-catalyzed asymmetric benzylic substitution of secondary benzyl
      carbonates with amides and amines proceeds to form the corresponding optically
      active benzylamines in good yields with a high enantiomeric ratio. The reaction
      occurs in a dynamic kinetic asymmetric transformation (DYKAT) manner.
      Additionally, the asymmetric Pd catalysis can also be applicable to phenol
      nucleophiles, thus delivering chiral ethers with acceptable yields and
      enantioselectivity.

PMID- 28447793
TI  - Hydrogen Peroxide-Induced Change in Meat Quality of the Breast Muscle of Broilers
      Is Mediated by ROS Generation, Apoptosis, and Autophagy in the NF-kappaB Signal
      Pathway.
AB  - We investigated the relationship between meat quality and oxidative damage caused
      by hydrogen peroxide (H2O2) in the breast muscle of broilers. Moreover, we
      explored the occurrence of apoptosis and autophagy, as well as the expression of
      NF-kappaB in these signaling pathways to provide evidence of possible oxidative
      damage mechanisms. The broilers received a basal diet and were randomly divided
      into five treatments (noninjected control, 0.75% saline-injected, and 2.5%, 5.0%,
      or 10.0% H2O2-injected treatments; 1.0 mL/kg in body weight). The results showed
      that oxidative stress induced by H2O2 had a negative effect on relative muscle
      weight, histomorphology, and redox status, while the underlying oxidative damage
      caused a decline in meat quality (decrease of pH24h, 10% H2O2 treatment; increase
      of shear force, 5% and 10% H2O2 treatments) of broilers. This could be attributed
      to the apoptosis and autophagy processes triggered by excessive reactive oxygen
      species that suppress the NF-kappaB signaling pathway.

PMID- 28447795
TI  - Chemisorbed and Physisorbed Water at the TiO2/Water Interface.
AB  - The interfacial structure of water in contact with TiO2 is the key to understand
      the mechanism of photocatalytic water dissociation as well as photoinduced
      superhydrophilicity. We investigate the interfacial molecular structure of water
      at the surface of anatase TiO2, using phase-sensitive sum frequency generation
      spectroscopy together with spectra simulation using ab initio molecular dynamic
      trajectories. We identify two oppositely oriented, weakly and strongly hydrogen
      bonded subensembles of O-H groups at the superhydrophilic UV irradiated TiO2
      surface. The water molecules with weakly hydrogen-bonded O-H groups are
      chemisorbed, i.e. form hydroxyl groups, at the TiO2 surface with their hydrogen
      atoms pointing toward bulk water. The strongly hydrogen-bonded O-H groups
      interact with the oxygen atom of the chemisorbed water. Their hydrogen atoms
      point toward the TiO2. This strong interaction between physisorbed and
      chemisorbed water molecules causes superhydrophilicity.

PMID- 28447796
TI  - Rhodium-Catalyzed Asymmetric Conjugate Alkynylation of beta,gamma-Unsaturated
      alpha-Ketoesters.
AB  - The first example of catalytic asymmetric conjugate alkynylation of beta,gamma
      unsaturated alpha-ketoesters is reported. By using Rh(I)/(R)-DM-binap complex as
      the catalyst and diphenyl[(triisopropylsilyl)ethynyl]methanol as the alkynylating
      reagent, the alkynylation reaction proceeded smoothly to afford alpha-ketoesters
      bearing a propargylic chiral center at gamma position in good yields with high
      enantioselectivities.

PMID- 28447797
TI  - Signal Transductions of BEAS-2B Cells in Response to Carcinogenic PM2.5 Exposure
      Based on a Microfluidic System.
AB  - PM2.5 (particulate matter less than 2.5 MUm in diameter) is considered as a
      harmful carcinogen. Determining the precise relationship between the chemical
      constituents of PM2.5 in the air and cancer progression could aid the treatment
      of environment related disease and establishing risk reduction strategies.
      Herein, we used transcriptomics (RNA-seq) and an integrated microfluidic system
      to identify the global gene expression and differential target proteins
      expression induced by ambient fine particles collected from the heavy haze in
      China. The results clearly indicated that cancer related pathways exhibited the
      strongest dysregulation. The ambient fine particles could be uptaken into the
      cells by pinocytosis, mainly promoting the PI3K-Akt pathway, FGF/FGFR/MAPK/VEGF
      signaling, and the JAK-STAT pathway, leading to evading apoptosis, sustained
      angiogenesis, and cell proliferation, which are the most important hallmarks of
      cancer. And fine particles also have been demonstrated to create intracellular
      reactive oxygen species (ROS) and mitochondrial ROS, change intracellular free
      Ca2+, and induce apoptosis, which are all key players in mediating cancer
      progression. It was observed by transmission electron microscopy (TEM) that the
      particles from the haze could enter the mitochondria, resulting in disturbance of
      the mitochondrial membrane and disruption of the mitochondria, and these
      particles can even enter inside the nucleus. It was also found in our study of
      organics (OC, PAHs) and metals (Zn, As, V) that compounds of fine particles were
      more closely associated with the exacerbation of cancer and secondary aerosols
      generated by traffic had the largest impact on cancer related signal
      transductions.

PMID- 28447798
TI  - Spontaneous Droplet Motion on a Periodically Compliant Substrate.
AB  - Droplet motion arises in many natural phenomena, ranging from the familiar
      gravity-driven slip and arrest of raindrops on windows to the directed transport
      of droplets for water harvesting by plants and animals under dry conditions.
      Deliberate transportation and manipulation of droplets are also important in many
      technological applications, including droplet-based microfluidic chemical
      reactors and for thermal management. Droplet motion usually requires gradients of
      surface energy or temperature or external vibration to overcome contact angle
      hysteresis. Here, we report a new phenomenon in which a drying droplet placed on
      a periodically compliant surface undergoes spontaneous, erratic motion in the
      absence of surface energy gradients and external stimuli such as vibration. By
      modeling the droplet as a mass-spring system on a substrate with periodically
      varying compliance, we show that the stability of equilibrium depends on the size
      of the droplet. Specifically, if the center of mass of the drop lies at a stable
      equilibrium point of the system, it will stay there until evaporation reduces its
      size and this fixed point becomes unstable; with any small perturbation, the
      droplet then moves to one of its neighboring fixed points.

PMID- 28447800
TI  - Stable Dihydrogen Complexes of Cobalt(-I) Suggest an Inverse trans-Influence of
      Lewis Acidic Group 13 Metalloligands.
AB  - A triad of d10 cobalt dihydrogen complexes was synthesized by utilizing Lewis
      acidic group 13 metalloligands, M[N((o-C6H4)NCH2PiPr2)3], where M = Al, Ga, and
      In. These complexes have formal Co(-I) oxidation states, representing the only
      coordination complexes in which dihydrogen is bound to a subvalent transition
      metal center. Single-crystal X-ray diffraction and NMR studies support the
      assignment of these complexes as nonclassical dihydrogen adducts of Co(-I).

PMID- 28447799
TI  - Enhanced Transdermal Delivery by Combined Application of Dissolving Microneedle
      Patch on Serum-Treated Skin.
AB  - Dissolving microneedle (DMN), a transdermal drug delivery system in which drugs
      are encapsulated in a biodegradable polymeric microstructure, is designed to
      dissolve after skin penetration and release the encapsulated drugs into the body.
      However, because of limited loading capacity of drugs within microsized
      structures, only a small dosage can be delivered, which is often insufficient for
      patients. We propose a novel DMN application that combines topical and DMN
      application simultaneously to improve skin permeation efficiency. Drugs in
      pretreated topical formulation and encapsulated drugs in DMN patch are delivered
      into the skin through microchannels created by DMN application, thus greatly
      increasing the delivered dose. We used 4-n-butylresorcinol to treat human
      hyperpigmentation and found that sequential application of serum formulation and
      DMNs was successful. In skin distribution experiments using Alexa Fluor 488 and
      568 dyes as model drugs, we confirmed that the pretreated serum formulation was
      delivered into the skin through microchannels created by the DMNs. In vitro skin
      permeation and retention experiments confirmed that this novel combined
      application delivered more 4-n-butylresorcinol into the skin than traditional DMN
      only and serum-only applications. Moreover, this combined application showed a
      higher efficacy in reducing patients' melanin index and hyperpigmented regions
      compared with the serum-only application. As combined application of DMNs on
      serum-treated skin can overcome both dose limitations and safety concerns, this
      novel approach can advance developments in transdermal drug delivery.

PMID- 28447801
TI  - Droplets on Microdecorated Surfaces: Evolution of the Polygonal Contact Line.
AB  - Interaction of liquids with surfaces is ubiquitous in our physical environment as
      well as many engineering applications. Recent advances on this topic have not
      only provided us with valuable insight into nature's design, but also enabled
      improved fluidic manipulation for liquid-based printing applications such as
      biomicroarrays for protein and DNA sequencing, multicolor polymer-based LED
      displays, inkjet printing, and solder droplet printing, among others. For
      example, droplet contact lines, which are typically circular on a smooth and
      homogeneous surface, when deposited on a microdecorated surface may take various
      common polygonal shapes such as squares, rectangles, hexagons, octagons and
      dodecagons. These polygonal contact line shapes are highly stable due to the
      local energy barriers associated with the anisotropy in depinning contact angles.
      In addition to the knowledge of the eventual contact line shapes, liquid-based
      printing applications would require accurate prediction of temporal evolution of
      contact line on these surfaces. In this work, we model and validate the evolution
      of droplets on microdecorated surfaces with microgoniometry experiments reported
      in the literature. We show that various metastable contact line shapes are formed
      in-between the well-known stable polygonal contact line shapes usually observed
      in experiments. We elucidate that the movement of the contact line between
      adjacent micropillars can primarily be categorized as primary zipping and
      transition zipping. Primary zipping occurs when the contact line moves radially
      outward to the next row of pillars, often resulting in the formation of a
      metastable contact line shape. Conversely, metastable droplet attains stable
      polygonal contact line shape via transition zipping wherein the contact line
      advances sideways. We believe that the current simulation approach can be
      effectively utilized for designing optimized textured surfaces for applications
      where control over liquid supply via surface design is required.

PMID- 28447803
TI  - Psychometrics and the neuroscience of individual differences: Internal
      consistency limits between-subjects effects.
AB  - In the clinical neuroscience literature, between-subjects differences in neural
      activity are presumed to reflect reliable measures-even though the psychometric
      properties of neural measures are almost never reported. The current article
      focuses on the critical importance of assessing and reporting internal
      consistency reliability-the homogeneity of "items" that comprise a neural
      "score." We demonstrate how variability in the internal consistency of neural
      measures limits between-subjects (i.e., individual differences) effects. To this
      end, we utilize error-related brain activity (i.e., the error-related negativity
      or ERN) in both healthy and generalized anxiety disorder (GAD) participants to
      demonstrate options for psychometric analyses of neural measures; we examine
      between-groups differences in internal consistency, between-groups effect sizes,
      and between-groups discriminability (i.e., ROC analyses)-all as a function of
      increasing items (i.e., number of trials). Overall, internal consistency should
      be used to inform experimental design and the choice of neural measures in
      individual differences research. The internal consistency of neural measures is
      necessary for interpreting results and guiding progress in clinical neuroscience
      and should be routinely reported in all individual differences studies. (PsycINFO
      Database Record

PMID- 28447804
TI  - Heightened attentional capture by visual food stimuli in anorexia nervosa.
AB  - The present study was designed to test the hypothesis that anorexia nervosa (AN)
      patients are relatively insensitive to the attentional capture of visual food
      stimuli. Attentional avoidance of food might help AN patients to prevent more
      elaborate processing of food stimuli and the subsequent generation of craving,
      which might enable AN patients to maintain their strict diet. Participants were
      66 restrictive AN spectrum patients and 55 healthy controls. A single-target
      rapid serial visual presentation task was used with food and disorder-neutral
      cues as critical distracter stimuli and disorder-neutral pictures as target
      stimuli. AN spectrum patients showed diminished task performance when visual food
      cues were presented in close temporal proximity of the to-be-identified target.
      In contrast to our hypothesis, results indicate that food cues automatically
      capture AN spectrum patients' attention. One explanation could be that the
      enhanced attentional capture of food cues in AN is driven by the relatively high
      threat value of food items in AN. Implications and suggestions for future
      research are discussed. (PsycINFO Database Record

PMID- 28447802
TI  - Potential Lipid-Lowering Mechanisms of Biochanin A.
AB  - Extensive studies have demonstrated that biochanin A (BCA) has a significant
      hypolipidemic effect. However, its mechanism of action is not clear. In this
      context, the effect of BCA on a high-fat diet (HFD)-induced hyperlipidemia in
      mice was determined. The results showed that treatment with a medium dose of
      biochanin A (BM) significantly decreased low-density lipoprotein cholesterol (LDL
      C) 85% (from 1.196 +/- 0.183 to 0.181 +/- 0.0778 mM) and total cholesterol (TC)
      39% (from 5.983 +/- 0.128 to 3.649 +/- 0.374 mM) levels, increased lipoprotein
      lipase (LPL) 96% (from 1.421 +/- 0.0982 to 2.784 +/- 0.177 U/mg protein) and
      hepatic triglyceride lipase (HTGL) 78% (from 1.614 +/- 0.0848 to 2.870 +/- 0.0977
      U/mg protein) activities, significantly improved fecal lipid levels, and lowered
      the epididymal fat index in hyperlipidemic mice compared with the HFD control
      mice (p < 0.05). In vitro, the high antioxidant capacity of BCA was determined by
      the FRAP assay, ABTS*+ scavenging method, and an ROS assay. In RAW 264.7
      macrophages, a dose of 10 MUM BCA significantly increased the cholesterol efflux
      by 18.7% compared with the control cells. Moreover, molecular docking of BCA on
      cholesterol ester transfer protein (CETP) (Asn24 and Thr27 at the N-terminal;
      Ala274 and Phe270 at the C-terminal) gave new insights into the role of BCA in
      preventing cholesterol ester transport.

PMID- 28447805
TI  - Do tiger keelback snakes (Rhabdophis tigrinus) recognize how toxic they are?
AB  - Animals that depend on defensive chemicals acquired from food may face a decision
      when attempting to deter predatory attacks: Should they exhibit antipredator
      behavior that relies on the toxicity of the sequestered chemicals or should they
      adopt other behaviors that can avoid predation without using the chemical
      defense, such as flight? Thus, it is reasonable to assume that animals that
      sequester prey toxins have evolved the ability to flexibly change their
      antipredator responses according to the amount of toxin-resource they have
      consumed. We tested this hypothesis using an Asian snake, Rhabdophis tigrinus,
      that sequesters toxins from toads consumed as food and stores them in specialized
      organs back of the head, called nuchal glands. We reared hatchling snakes from
      toad-free and toad-rich islands on controlled diets and examined their subsequent
      antipredator responses after 3 and 6 month feeding. Juveniles from a toad-free
      island that had been fed a diet including toads for 3 months showed antipredator
      displays associated with the nuchal glands more frequently than those that had
      been fed a diet without toads. They showed a similar, but less clear, tendency
      after 6 months feeding. Juveniles from the toad-rich island did not show a clear
      tendency of dietary effect. We discuss possible reasons for the different dietary
      effects between the 2 populations and between the ages. Our results, along with
      previous related phenomena in other animals, suggest that the ability of self
      toxicity-recognition may be widespread in animals that sequester defensive toxins
      from facultative food. (PsycINFO Database Record

PMID- 28447806
TI  - Blame, coping, and psychosocial outcomes in caregivers of individuals with brain
      injury.
AB  - OBJECTIVE: Acquired brain injury (ABI) is associated with many physical and
      psychiatric conditions. Oftentimes, the individual's family members are
      responsible for providing long-term care, leaving caregivers vulnerable to
      negative effects of caregiving including stress, depression, and decreased
      quality of life. Attribution theory suggests that caregivers may blame the
      individual with the ABI for their injury as a way to understand their own
      circumstances. The objective of this study was to investigate caregiver coping
      strategies as possible mediators between caregiver family member blame and
      caregiver psychosocial outcomes among caregivers of individuals with ABI. METHOD:
      Caregivers of individuals with ABI (n = 94) completed an online survey of self
      report measures regarding coping (emotion-focused, problem-focused, and
      dysfunctional strategies), blame (direct, indirect, and preoccupation with
      blame), depressive symptoms, and quality of life (QOL). Bootstrapping mediation
      analyses were conducted to investigate the mediating role of caregiver coping
      strategies between blame attributions, and either depressive symptoms or QOL.
      RESULTS: Results demonstrated that the use of more dysfunctional coping
      strategies significantly mediated the relationship between indirect blame, and
      depressive symptoms and QOL. Furthermore, using more dysfunctional coping
      strategies also significantly mediated the relationship between preoccupation
      with blame and depressive symptoms. CONCLUSIONS: Results of this study point to
      the important role blame attributions play in the use of coping strategies and
      subsequent psychosocial outcomes. By understanding the relationships between
      blame attributions, coping behavior, and psychosocial outcomes, clinicians may
      better tailor treatments to optimize QOL and promote the psychological well being
      of caregivers and care recipients. (PsycINFO Database Record

PMID- 28447807
TI  - Developing a measure to assess identity reconstruction in patients with multiple
      sclerosis.
AB  - PURPOSE/OBJECTIVE: To develop and test initial validation of a theory-driven
      quantitative measure of identity reconstruction in patients with multiple
      sclerosis (MS) based upon previous qualitative research. Research Method/Design:
      This study uses a cross-sectional survey design, in which 137 patients living
      with MS were recruited from an outpatient MS Center in the Southeastern U.S.
      Participants completed demographic items, Identity Reconstruction Assessment
      Scales (IRAS), Patient Determined Disease Steps, Medical Outcomes Study Measures
      of Patient Adherence, Chronic Disease Self-Efficacy Scale, Hospital Anxiety and
      Depression Scale, Leeds MS Quality of Life Questionnaire, MS-Related Stigma
      Scale, and Posttraumatic Growth Inventory-Short Form. RESULTS: The IRAS conformed
      to a 3-factor solution consisting of 23 items accounting for 42.6% of the
      variance. The 3 factors, labeled as "sustained identity" (alpha = .84),
      "reactionary identity" (alpha = .74), and "integrated identity" (alpha = .65),
      were not significantly correlated with each other, necessitating and allowing for
      independent scoring of the scales. Higher scores on "sustained identity" scale
      were associated with less anxiety, depression, perceived disability, and MS
      related stigma, as well as with increased self-efficacy, treatment adherence, and
      quality of life. "Reactionary identity" scale was positively correlated with
      anxiety and MS-related stigma. "Integrated identity" was significantly associated
      with age and perceived disability. CONCLUSIONS/IMPLICATIONS: Identity
      reconstruction provides needed context for understanding adjustment to and living
      with MS. Examination of the IRAS within a larger sample and in other disease
      groups can provide additional construct validity evidence. (PsycINFO Database
      Record

PMID- 28447809
TI  - Understanding the cognitive processes involved in writing to learn.
AB  - Writing is often used as a tool for learning. However, empirical support for the
      benefits of writing-to-learn is mixed, likely because the literature conflates
      diverse activities (e.g., summaries, term papers) under the single umbrella of
      writing-to-learn. Following recent trends in the writing-to-learn literature, the
      authors focus on the underlying cognitive processes. They draw on the largely
      independent writing-to-learn and cognitive psychology learning literatures to
      identify important cognitive processes. The current experiment examines learning
      from 3 writing tasks (and 1 nonwriting control), with an emphasis on whether or
      not the tasks engaged retrieval. Tasks that engaged retrieval (essay writing and
      free recall) led to better final test performance than those that did not (note
      taking and highlighting). Individual differences in structure building (the
      ability to construct mental representations of narratives; Gernsbacher, Varner, &
      Faust, 1990) modified this effect; skilled structure builders benefited more from
      essay writing and free recall than did less skilled structure builders. Further,
      more essay-like responses led to better performance, implicating the importance
      of additional cognitive processes such as reorganization and elaboration. The
      results highlight how both task instructions and individual differences affect
      the cognitive processes involved when writing-to-learn, with consequences for the
      effectiveness of the learning strategy. (PsycINFO Database Record

PMID- 28447808
TI  - Posttraumatic stress disorder after spinal cord injury.
AB  - OBJECTIVE: The objective of the study was to identify the relationships of
      demographics, injury-related characteristics, employment, depressive symptoms,
      and health events with posttraumatic stress disorder (PTSD) among participants
      with spinal cord injury. RESEARCH METHOD: A total of 1,063 participants were
      recruited from 3 sites in different regions (Southeastern, Mountain, and Western)
      of the United States. Hispanics and non-Hispanic Blacks were oversampled. Three
      hundred sixty-nine were non-Hispanic White, followed by 361 non-Hispanic Black,
      277 Hispanic, and 56 from other racial-ethnic groups. PTSD was measured by the
      Purdue PTSD Scale-Revised. All variables were measured by self-report.
      Multivariate logistic regression models were developed to assess the association
      between PTSD and multiple variables. RESULTS: The overall prevalence of PTSD
      across all participants was 24.9%, and the mean PTSD score of all participants
      was 34.7 (SD = 14.6). PTSD was associated with depression, frequency of
      medication use for depression or stress, number of times receiving medical care
      because of injury in the past year, and race-ethnicity (lower among non-Hispanic
      Whites). CONCLUSIONS: PTSD was relatively prevalent in this study. PTSD was
      highly comorbid with depressive disorders and associated with post-spinal cord
      injuries within the previous year. (PsycINFO Database Record

PMID- 28447811
TI  - Likelihood-based parameter estimation and comparison of dynamical cognitive
      models.
AB  - Dynamical models of cognition play an increasingly important role in driving
      theoretical and experimental research in psychology. Therefore, parameter
      estimation, model analysis and comparison of dynamical models are of essential
      importance. In this article, we propose a maximum likelihood approach for model
      analysis in a fully dynamical framework that includes time-ordered experimental
      data. Our methods can be applied to dynamical models for the prediction of
      discrete behavior (e.g., movement onsets); in particular, we use a dynamical
      model of saccade generation in scene viewing as a case study for our approach.
      For this model, the likelihood function can be computed directly by numerical
      simulation, which enables more efficient parameter estimation including Bayesian
      inference to obtain reliable estimates and corresponding credible intervals.
      Using hierarchical models inference is even possible for individual observers.
      Furthermore, our likelihood approach can be used to compare different models. In
      our example, the dynamical framework is shown to outperform nondynamical
      statistical models. Additionally, the likelihood based evaluation differentiates
      model variants, which produced indistinguishable predictions on hitherto used
      statistics. Our results indicate that the likelihood approach is a promising
      framework for dynamical cognitive models. (PsycINFO Database Record

PMID- 28447810
TI  - Surviving blind decomposition: A distributional analysis of the time-course of
      complex word recognition.
AB  - The current study addresses a discrepancy in the psycholinguistic literature
      about the chronology of information processing during the visual recognition of
      morphologically complex words. Form-then-meaning accounts of complex word
      recognition claim that morphemes are processed as units of form prior to any
      influence of their meanings, whereas form-and-meaning models posit that
      recognition of complex word forms involves the simultaneous access of
      morphological and semantic information. The study reported here addresses this
      theoretical discrepancy by applying a nonparametric distributional technique of
      survival analysis (Reingold & Sheridan, 2014) to 2 behavioral measures of complex
      word processing. Across 7 experiments reported here, this technique is employed
      to estimate the point in time at which orthographic, morphological, and semantic
      variables exert their earliest discernible influence on lexical decision RTs and
      eye movement fixation durations. Contrary to form-then-meaning predictions,
      Experiments 1-4 reveal that surface frequency is the earliest lexical variable to
      exert a demonstrable influence on lexical decision RTs for English and Dutch
      derived words (e.g., badness; bad + ness), English pseudoderived words (e.g.,
      wander; wand + er) and morphologically simple control words (e.g., ballad; ball +
      ad). Furthermore, for derived word processing across lexical decision and eye
      tracking paradigms (Experiments 1-2; 5-7), semantic effects emerge early in the
      time-course of word recognition, and their effects either precede or emerge
      simultaneously with morphological effects. These results are not consistent with
      the premises of the form-then-meaning view of complex word recognition, but are
      convergent with a form-and-meaning account of complex word recognition. (PsycINFO
      Database Record

PMID- 28447813
TI  - Using response time data to reduce testing time in cognitive tests.
AB  - Achievement estimates are often based on either number correct scores or IRT
      based ability parameters. Van der Linden (2007) and other researchers (e.g., Fox,
      Klein Entink, & van der Linden, 2007; Ranger, 2013) have developed psychometric
      models that allow for joint estimation of speed and item parameters using both
      response times and response data. This paper presents an application of this type
      of approach to a battery of 4 types of fluid reasoning measures, administered to
      a large sample of a highly educated examinees. We investigate the extent to which
      incorporation of response times in ability estimates can be used to inform the
      potential development of shorter test forms. In addition to exploratory analyses
      and response time data visualizations, we specifically consider the increase in
      precision of ability estimates given the addition of response time data relative
      to use of item responses alone. Our findings indicate that there may be instances
      where test forms can be substantially shortened without any reduction in score
      reliability, when response time information is incorporated into the item
      response model. (PsycINFO Database Record

PMID- 28447812
TI  - A computational model of fraction arithmetic.
AB  - Many children fail to master fraction arithmetic even after years of instruction,
      a failure that hinders their learning of more advanced mathematics as well as
      their occupational success. To test hypotheses about why children have so many
      difficulties in this area, we created a computational model of fraction
      arithmetic learning and presented it with the problems from a widely used
      textbook series. The simulation generated many phenomena of children's fraction
      arithmetic performance through a small number of common learning mechanisms
      operating on a biased input set. The biases were not unique to this textbook
      series-they were present in 2 other textbook series as well-nor were the
      phenomena unique to a particular sample of children-they were present in another
      sample as well. Among other phenomena, the model predicted the high difficulty of
      fraction division, variable strategy use by individual children and on individual
      problems, relative frequencies of different types of strategy errors on different
      types of problems, and variable effects of denominator equality on the four
      arithmetic operations. The model also generated nonintuitive predictions
      regarding the relative difficulties of several types of problems and the
      potential effectiveness of a novel instructional approach. Perhaps the most
      general lesson of the findings is that the statistical distribution of problems
      that learners encounter can influence mathematics learning in powerful and
      nonintuitive ways. (PsycINFO Database Record

PMID- 28447814
TI  - Undetected scars? Self-criticism, attachment, and romantic relationships among
      otherwise well-functioning childhood sexual abuse survivors.
AB  - BACKGROUND: Studies have consistently demonstrated the negative impact of
      childhood sexual abuse (CSA) on intimate relationships. The majority of studies
      have focused on revictimization in at-risk or clinical samples, with very few
      addressing the impact of CSA on otherwise well-functioning adults and even fewer
      investigating the psychological mechanisms involved. To fill this gap, this study
      focuses on the effect of CSA on "normative" (nonviolent) romantic relationships
      in otherwise well-functioning young women, and the mediating role of personality
      dimension self-criticism and attachment in this regard. Specifically, we
      investigate whether self-criticism and attachment avoidance mediate the
      relationship between CSA and romantic relationship satisfaction, while also
      examining the potential reciprocal associations between these variables. METHOD:
      The hypothesized mediation model was examined in a 2-wave, 6-month, cross-lagged
      longitudinal design, using structural equation modeling. Participants were 59
      well-functioning (psychologically, socially, occupationally) young women drawn
      from an earlier study that purposefully oversampled for CSA survivors. For the
      purpose of the current study, data from women who had been either sexually abused
      by a familiar perpetrator (n = 30) or had no history of sexual trauma (n = 29)
      were included. RESULTS: Consistent with expectations, self-criticism mediated the
      association between CSA and romantic relationship satisfaction over time. In
      addition, a scarring effect of romantic relationship satisfaction on attachment
      avoidance was demonstrated. CONCLUSION: Findings suggest that CSA may lead to
      elevated levels of self-criticism, which in turn may be linked with reduced
      satisfaction in romantic relationships, setting in motion a vicious cycle
      involving relationship satisfaction and attachment avoidance. (PsycINFO Database
      Record

PMID- 28447815
TI  - Development of the Healthcare Triggering Questionnaire in adult sexual abuse
      survivors.
AB  - OBJECTIVE: One in 4 women and 1 in 10 men in the United States are survivors of
      sexual abuse (SA). For these survivors, healthcare experiences may trigger
      memories, thoughts, feelings or sensations related to this past abuse. Such
      triggering can be associated with negative responses to healthcare (e.g.,
      anxiety, avoidance). However, to date, no healthcare triggering assessment tool
      exists. Therefore, the study goal was to describe the prevalence of healthcare
      triggering, to develop a brief Healthcare Triggering Questionnaire (HTQ), and to
      examine its initial validity. METHOD: An initial pool of 117 items was developed
      based on previous research. Two-parameter logistic item response theory models
      were used to develop the scales. SA survivors [male (n = 233), female (n = 222)]
      and a comparison group of non-SA individuals [male (n = 114), female (n = 106)]
      were recruited through Amazon Mechanical Turk and completed the study anonymously
      online. RESULTS: Three 10-item scales were developed: (a) the HTQ-M for males;
      (b) the HTQ-F for females; and (c) the HTQ-U (unisex) for all respondents. The
      results supported the utility and initial validity of the gender-specific and
      unisex scales. CONCLUSIONS: The HTQ scales are a psychometrically sound approach
      to evaluating healthcare triggering experienced by adult sexual abuse survivors.
      The HTQ may be considered for use by researchers interested in studying
      healthcare triggering, healthcare retraumatization, and healthcare adherence. The
      HTQ may also be of use to clinicians interested in identifying trauma survivors
      who are more likely to experience triggering in healthcare settings. (PsycINFO
      Database Record

PMID- 28447816
TI  - Does combat exposure affect well-being in later life? The VA Normative Aging
      Study.
AB  - OBJECTIVE: Combat exposure can have long-term negative effects in later life;
      although aspects of service may be appraised positively, the long-term positive
      effects of combat on well-being in later life is largely unknown. METHOD: The
      sample included 1,006 male veterans from the VA Normative Aging Study, surveyed
      by mail in 1986, 1990, and 1991 (Mage = 65.5 years, SD = 7.3). They reported on
      their combat exposure, desirable appraisals of military service, unit cohesion,
      dispositional optimism, self-rated health, and psychological well-being (PWB), as
      well as age, military rank, and education. Perceived positive aspects (PPA) of
      military service was postulated to mediate the effects of combat exposure on PWB.
      Structural equation modeling was used to examine both mediating and moderating
      effects. RESULTS: Age, combat exposure, and optimism had independent effects on
      PPA, but optimism did not moderate the effect of combat exposure on PPA. Combat
      exposure had only indirect effects on PWB through PPA, controlling for the direct
      effects of optimism. Education had no direct effects on the positive outcomes but
      did have indirect effects through optimism. CONCLUSION: Combat exposure
      contributes to positive well-being in later life, indirectly through positive
      appraisals, and this effect was independent of optimism. Thus, these results
      support the idea that combat veterans should be encouraged to focus on positive
      aspects of military service, which may serve as resilience resources to
      facilitate optimal aging. (PsycINFO Database Record

PMID- 28447817
TI  - A unified framework for bounded and unbounded numerical estimation.
AB  - Representations of numerical value have been assessed by using bounded (e.g., 0
      1,000) and unbounded (e.g., 0-?) number-line tasks, with considerable debate
      regarding whether 1 or both tasks elicit unique cognitive strategies (e.g.,
      addition or subtraction) and require unique cognitive models. To test this, we
      examined how well a mixed log-linear model accounted for 86 5- to 9-year-olds'
      estimates on bounded and unbounded number-line tasks and how well it predicted
      mathematical performance. Compared with mixtures of 4 alternative models, the
      mixed log-linear model better predicted 76% of individual children's estimates on
      bounded number lines and 100% of children's estimates on unbounded number lines.
      Furthermore, the distribution of estimates was fit better by a Bayesian log
      linear model than by a Bayesian distributional model that depicted estimates as
      being anchored to varying number of reference points. Finally, estimates were
      generally more logarithmic on unbounded than bounded number lines, but
      logarithmicity scores on both tasks predicted addition and subtraction skills,
      whereas model parameters of alternative models failed to do so. Results suggest
      that the logarithmic-to-linear shift theory provides a simple, unified framework
      for numerical estimation with high descriptive adequacy and yields uniquely
      accurate predictions for children's early math proficiency. (PsycINFO Database
      Record

PMID- 28447818
TI  - "Hard-earned wisdom: Exploratory processing of difficult life experience is
      positively associated with wisdom": Correction to Weststrate and Gluck (2017).
AB  - Reports an error in "Hard-earned wisdom: Exploratory processing of difficult life
      experience is positively associated with wisdom" by Nic M. Weststrate and Judith
      Gluck (Developmental Psychology, 2017[Apr], Vol 53[4], 800-814). The affiliation
      of Nic M. Weststrate was inadvertently set as "Relationships and Life
      Experiences" in the article byline. It should have been "University of Toronto".
      The online version of this article has been corrected. (The following abstract of
      the original article appeared in record 2017-12497-007.) Laypersons and experts
      believe that wisdom is cultivated through a diverse range of positive and
      negative life experiences. Yet, not all individuals with life experience are
      wise. We propose that one possible determinant of growth in wisdom from life
      experience is self-reflection. In a life span sample of adults (N = 94) ranging
      from 26 to 92 years of age, we examined wisdom's relationship to self-reflection
      by investigating "why" people report reflecting on the past (i.e., reminiscence
      functions) and "how" they reflect within autobiographical memories of difficult
      life events (i.e., autobiographical reasoning). We assessed wisdom using self
      report, performance, and nomination approaches. Results indicated that wisdom was
      unrelated to the frequency of self-reflection; however, wiser people differed
      from others in their (a) reasons for reminiscence and (b) mode of
      autobiographical reasoning. Across 3 methods for assessing wisdom, wisdom was
      positively associated with exploratory processing of difficult life experience
      (meaning-making, personal growth), whereas redemptive processing (positive
      emotional reframing, event resolution) was positively associated with adjustment.
      This study suggests that developmental pathways in the wake of adversity may be
      partially determined by how individuals self-reflectively process significant
      life experiences. (PsycINFO Database Record

PMID- 28447819
TI  - Intelligence, income, and education as potential influences on a child's home
      environment: A (maternal) sibling-comparison design.
AB  - The quality of the home environment, as a predictor, is related to health,
      education, and emotion outcomes. However, factors influencing the quality of the
      home environment, as an outcome, have been understudied-particularly how children
      construct their own environments. Further, most previous research on family
      processes and outcomes has implemented between-family designs, which limit claims
      of causality. The present study uses kinship data from the National Longitudinal
      Survey of Youth to construct a maternal sibling-comparison design to investigate
      how maternal and child traits predict the quality of home environment. Using a
      standard between-family analysis, we first replicate previous research showing a
      relationship between maternal intelligence and the quality of the home
      environment. Then, we reevaluate the link between maternal intelligence and the
      home environment using differences between maternal sisters on several
      characteristics to explain differences between home environments for their
      children. Following, we evaluate whether child intelligence differences are
      related to home environment differences in the presence of maternal
      characteristics. Results are compared with those from the between-family
      analysis. Past causal interpretations are challenged by our findings, and the
      role of child intelligence in the construction of the home environment emerges as
      a critical contributor that increases in importance with development. (PsycINFO
      Database Record

PMID- 28447820
TI  - Are peer specialists happy on the job?
AB  - OBJECTIVE: This study was designed to examine the impact of role clarity and job
      training on job satisfaction among peer specialists. METHOD: A 3-part survey
      assessing job training, job satisfaction, and role clarity was administered
      online to 195 peer specialists who are members of the International Association
      of Peer Specialists. Data was analyzed using descriptive statistics,
      correlational analyses to include multiple linear regressions and analysis of
      variance. RESULTS: Self-study and online training methods were negatively
      correlated with job satisfaction while job shadowing was positively correlated
      with job satisfaction. Role clarity was positively correlated with job
      satisfaction and job training satisfaction as well as job shadowing and one-on
      one training. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The use of self-study
      and online training for peer specialists is contraindicated by current findings,
      which suggest the need to utilize job shadowing or training methods that allow
      for personal interaction between peer specialists and their colleagues. (PsycINFO
      Database Record

PMID- 28447821
TI  - Intersectional policy analysis of self-directed mental health care in Canada.
AB  - OBJECTIVE: Recovery from mental illness is influenced by one's social location
      along multiple dimensions of identity, such as race, class, gender, age, and
      ability, and by how these social locations are expressed through structural and
      institutional barriers. This project was developed using an intersectional policy
      analysis framework designed to promote equity across identity locations-called
      the multistrand method-to examine the potential use of self-directed care
      financing approaches in the Canadian mental health system. METHOD: A panel of 16
      diverse stakeholders came together 4 times at structured 6-hr meetings to examine
      the evidence for self-directed care and explore its application in the Canadian
      context. Telephone interviews with evidence panel members were conducted to
      assess their perceptions of the group process and outcomes. RESULTS: Our analysis
      revealed ways that intersecting strand locations might differentially influence
      the degree of choice and recovery experienced by self-directed care participants.
      Individualized resource allocation, draining financial resources from ethnically
      specific services, unevenness in acceptance of the recovery orientation, and
      paucity of service options in different geographical regions were identified as
      contexts in which self-directed care policies could promote inequity. However,
      greater peer involvement in the model's implementation, use of indigenous
      community supports, purchase of material goods by economically disenfranchised
      persons, and access to services from ethnically diverse clinicians in the private
      sector were identified as equity-promoting model features. CONCLUSION AND
      IMPLICATIONS FOR PRACTICE: By couching their analysis at the level of unique
      socially-situated perspectives, the group developed detailed policy
      recommendations and insights into both the potential and limitations of self
      directed care. The knowledge gained from our project can be used to develop
      uniquely Canadian self-directed care models tailored to promote recovery through
      empowerment and self-determination across intersecting identity strand locations.
      (PsycINFO Database Record

PMID- 28447822
TI  - Social cognition, internalized stigma, and recovery orientation among adults with
      serious mental illness.
AB  - OBJECTIVE: The social-cognitive model is useful in understanding internalized
      stigma, but research has not examined it in relationship to recovery orientation,
      an important outcome. This study examined the impact of the four stages of
      internalized stigma on recovery orientation and assessed cognitive insight as a
      moderator. METHOD: Data from a community sample of adults with serious mental
      illness (N = 268) were collected through structured interviews. Regression-based
      analyses were used to examine the main effects of internalized stigma on recovery
      orientation and the moderating effect of cognitive insight. RESULTS: Applying
      stigmatizing beliefs to oneself and the related decrement in self-esteem each
      predicted decreased recovery orientation. Cognitive insight moderated the effect
      of self-application of stigmatizing beliefs on recovery orientation.
      IMPLICATIONS: Increasing cognitive insight by fostering flexibility in self
      cognitions may help reduce internalized stigma. Interventions may also benefit
      from addressing the emotional component of internalized stigma, such as feelings
      of shame. (PsycINFO Database Record

PMID- 28447823
TI  - The promise of demand side employer-based strategies to increase employment rates
      for people living with serious mental illnesses.
AB  - OBJECTIVE: This article describes current and promising demand-side strategies to
      increase job retention and employment rates of people living with serious mental
      illnesses. The article raises awareness of the potential impact of demand side
      strategies and generates considerations to implement and evaluate these
      strategies. METHOD: Information is drawn from peer reviewed research, policy
      articles and documents, and the authors' direct experiences. RESULTS: Employees
      with serious mental illnesses struggle to retain jobs due to workplace stigma,
      difficulty accessing reasonable accommodations, and noneligibility for health
      benefits. The traditional focus of vocational services on direct individualized
      supports has not addressed these employer-based challenges. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: The federal government, primarily through the
      Workforce Innovation and Opportunity Act, is increasing resources to guide
      businesses to adopt best practices for employing people with serious mental
      illnesses. Financial incentives, such as tax credits for hiring people with
      disabilities, are considered vital toward employers' cooperation. (PsycINFO
      Database Record

PMID- 28447824
TI  - "Similar representations of emotions across faces and voices": Correction to Kuhn
      et al. (2017).
AB  - Reports an error in "Similar Representations of Emotions Across Faces and Voices"
      by Lisa Katharina Kuhn, Taeko Wydell, Nadine Lavan, Carolyn McGettigan and Lucia
      Garrido (Emotion, Advanced Online Publication, Mar 02, 2017, np). In the article,
      the copyright attribution was incorrectly listed and the Creative Commons CC-BY
      license disclaimer was incorrectly omitted from the author note. The correct
      copyright is "(c) 2017 The Author(s)" and the omitted disclaimer is below. All
      versions of this article have been corrected. "This article has been published
      under the terms of the Creative Commons Attribution License
      (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use,
      distribution, and reproduction in any medium, provided the original author and
      source are credited. Copyright for this article is retained by the author(s).
      Author(s) grant(s) the American Psychological Association the exclusive right to
      publish the article and identify itself as the original publisher." (The
      following abstract of the original article appeared in record 2017-09406-001.)
      Emotions are a vital component of social communication, carried across a range of
      modalities and via different perceptual signals such as specific muscle
      contractions in the face and in the upper respiratory system. Previous studies
      have found that emotion recognition impairments after brain damage depend on the
      modality of presentation: recognition from faces may be impaired whereas
      recognition from voices remains preserved, and vice versa. On the other hand,
      there is also evidence for shared neural activation during emotion processing in
      both modalities. In a behavioral study, we investigated whether there are shared
      representations in the recognition of emotions from faces and voices. We used a
      within-subjects design in which participants rated the intensity of facial
      expressions and nonverbal vocalizations for each of the 6 basic emotion labels.
      For each participant and each modality, we then computed a representation matrix
      with the intensity ratings of each emotion. These matrices allowed us to examine
      the patterns of confusions between emotions and to characterize the
      representations of emotions within each modality. We then compared the
      representations across modalities by computing the correlations of the
      representation matrices across faces and voices. We found highly correlated
      matrices across modalities, which suggest similar representations of emotions
      across faces and voices. We also showed that these results could not be explained
      by commonalities between low-level visual and acoustic properties of the stimuli.
      We thus propose that there are similar or shared coding mechanisms for emotions
      which may act independently of modality, despite their distinct perceptual
      inputs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

PMID- 28447825
TI  - Enhanced processing of untrustworthiness in natural faces with neutral
      expressions.
AB  - During social interactions, individuals rapidly and automatically judge others'
      trustworthiness on the basis of subtle facial cues. To investigate the behavioral
      and neural correlates of these judgments, we conducted 2 studies: 1 study for the
      construction and evaluation of a set of natural faces differing in
      trustworthiness (Study 1: n = 30) and another study for the investigation of
      event-related potentials (ERPs) in response to this set of natural faces (Study
      2: n = 30). Participants of both studies provided highly reliable and nearly
      identical trustworthiness ratings for the selected faces, supporting the notion
      that the discrimination of trustworthy and untrustworthy faces depends on
      distinct facial cues. These cues appear to be processed in an automatic and
      bottom-up-driven fashion because the free viewing of these faces was sufficient
      to elicit trustworthiness-related differences in late positive potentials (LPPs)
      as indicated by larger amplitudes to untrustworthy as compared with trustworthy
      faces. Taken together, these findings suggest that natural faces contain distinct
      cues that are automatically and rapidly processed to facilitate the
      discrimination of untrustworthy and trustworthy faces across various contexts,
      presumably by enhancing the elaborative processing of untrustworthy as compared
      with trustworthy faces. (PsycINFO Database Record

PMID- 28447826
TI  - The role of expectations and habitual emotion regulation in emotional processing:
      An ERP investigation.
AB  - Available evidence from separate lines of event-related potential (ERP) research
      has highlighted the role of expectations and emotion regulation on emotional
      processing by revealing that (i) expectations can alter emotional responses, and
      (ii) the instructed use of emotion regulation strategies may modulate emotional
      responses. Yet, little is known about the interplay between expectations and
      habitual emotion regulation strategies prior to and at the onset of an emotional
      event. The present study aimed to investigate this potential relationship.
      Participants completed an affective-cueing task consisting of cues (red squares
      and blue circles) signaling the likely valence of upcoming target images
      (negative or neutral). This task allowed us to examine the impact of expectations
      at 2 temporal stages, Cue Interval and Target Interval, by measuring the late
      positive potential (LPP) as an index of emotional processing. Habitual use of
      emotion regulation strategies was assessed through the Emotion Regulation
      Questionnaire (ERQ), which measures the use of cognitive reappraisal and
      expressive suppression in everyday life. In the Cue Interval, LPP amplitude was
      greater for negative versus neutral cues (p < .001). In the Target Interval, LPP
      amplitude was greater for negatively cued versus neutrally cued targets,
      regardless of target valence (p = .003). ERQ reappraisal, but not suppression,
      negatively correlated with LPP modulation as a function of cue valence during
      both intervals (ps < .05). These findings provide novel insights regarding the
      interplay between expectations and habitual emotion regulation in emotional
      processing both prior to and at the onset of an emotional event. (PsycINFO
      Database Record

PMID- 28447829
TI  - Attributes of conscientiousness throughout the animal kingdom: An empirical and
      evolutionary overview.
AB  - Conscientiousness is a fundamental aspect of human personality, one that is
      closely linked with various favorable life outcomes. Despite its importance in
      humans, conscientiousness has received little attention as to how it may have
      evolved, or whether it provides similar fitness benefits in other animals. To
      date, research in animal personality has found consistent support for the
      presence of all major dimensions of human personality in other animals except
      conscientiousness. In this review, we investigate conscientiousness at the level
      of traits and facets (clusters of closely related traits). A systematic review of
      the literature retrieved 876 relevant publications describing attributes of
      conscientiousness in other animal species. A factor analysis of citation counts
      revealed 2 major dimensions representing 9 distinct facets of conscientiousness
      in nonhumans. These facets, together with their underlying personality traits,
      exhibit individual variability, are generally known to be heritable, and often
      offer clear fitness benefits to individuals. Other facets of conscientiousness
      appear to be unique to humans. Publication biases, research biases, and
      anthropomorphism may all play a role in the structure of the evidence we report.
      We conclude by suggesting fruitful areas of future research to further elucidate
      the presence and functional roles of conscientiousness in animals. (PsycINFO
      Database Record

PMID- 28447827
TI  - Interpersonal dysfunction in personality disorders: A meta-analytic review.
AB  - Personality disorders are defined in the current psychiatric diagnostic system as
      pervasive, inflexible, and stable patterns of thinking, feeling, behaving, and
      interacting with others. Questions regarding the validity and reliability of the
      current personality disorder diagnoses prompted a reconceptualization of
      personality pathology in the most recent edition of the psychiatric diagnostic
      manual, in an appendix of emerging models for future study. To evaluate the
      construct and discriminant validity of the current personality disorder
      diagnoses, we conducted a quantitative synthesis of the existing empirical
      research on associations between personality disorders and interpersonal
      functioning, defined using the interpersonal circumplex model (comprising
      orthogonal dimensions of agency and communion), as well as functioning in
      specific relationship domains (parent-child, family, peer, romantic). A
      comprehensive literature search yielded 127 published and unpublished studies,
      comprising 2,579 effect sizes. Average effect sizes from 120 separate meta
      analyses, corrected for sampling error and measurement unreliability, and
      aggregated using a random-effects model, indicated that each personality disorder
      showed a distinct profile of interpersonal style consistent with its
      characteristic pattern of symptomatic dysfunction; specific relationship domains
      affected and strength of associations varied for each personality disorder.
      Overall, results support the construct and discriminant validity of the
      personality disorders in the current diagnostic manual, as well as the proposed
      conceptualization that disturbances in self and interpersonal functioning
      constitute the core of personality pathology. Importantly, however, contradicting
      both the current and proposed conceptualizations, there was not evidence for
      pervasive dysfunction across interpersonal situations and relationships.
      (PsycINFO Database Record

PMID- 28447830
TI  - Managing a perilous stigma: Ex-offenders' use of reparative impression management
      tactics in hiring contexts.
AB  - Individuals with a criminal record face employment challenges because of the
      nature of their stigma. In this study, we examined the efficacy of using
      reparative impression management tactics to mitigate integrity concerns
      associated with a perilous stigma. Drawing on affect control theory, we proposed
      that the use of 3 impression management tactics-apology, justification, excuse
      would differentially affect hiring evaluations through their influence on
      perceived remorse and anticipated workplace deviance. Across 3 studies, we found
      support for our proposed model. Our results revealed the use of an apology or
      justification tactic when explaining a previous criminal offense had a positive
      indirect effect on hiring evaluations, whereas the use of an excuse tactic had a
      negative indirect effect. These findings suggest applicants may benefit from
      using impression management tactics that communicate remorse when discussing
      events or associations that violate integrity expectations. (PsycINFO Database
      Record

PMID- 28447831
TI  - Fuse or fracture? Threat as a moderator of the effects of diversity faultlines in
      teams.
AB  - While faultlines theory has received quite a bit of attention in the literature,
      there has been some inconsistency in findings regarding identity and information
      faultlines. Namely, identity faultlines do not always result in harmful social
      categorizations and information faultlines do not always increase information
      processing capabilities. However, according to the categorization-elaboration
      model (CEM; van Knippenberg, De Dreu, & Homan, 2004), any category of diversity
      can result in categorization processes and intergroup bias. One key to
      understanding faultlines, therefore, lies in context-specific predictions.
      Building on this idea, we apply the CEM as an explanatory framework and examine
      threat as a contextual moderator of identity and information faultlines. We
      propose that threat mitigates the negative effects of activated identity
      faultlines on team creativity: an effect mediated by team psychological safety.
      In contrast, we propose that threat aggravates the negative effects of
      information faultlines on team decision-making: an effect mediated by status
      conflict. We test our hypotheses with 2 experiments and 184 teams, finding
      support for our predictions regarding identity faultlines and partial support for
      our predictions regarding information faultlines. Taken together, this study
      demonstrates the utility of the CEM for faultlines research, identifies an
      important boundary condition of the effects of identity and information
      faultlines, and challenges the notion that threat is always "bad" for teams.
      (PsycINFO Database Record

PMID- 28447832
TI  - The role of political affiliation in employment decisions: A model and research
      agenda.
AB  - Organizational researchers have studied how individuals identify with groups and
      organizations and how this affiliation influences behavior for decades (e.g.,
      Tajfel, 1982). Interestingly, investigation into political affiliation and
      political affiliation similarity in the organizational sciences is extremely
      rare. This is striking, given the deep political divides that exist between
      groups of individuals described in the political science literature. We draw from
      theories based on similarity, organizational identification, and person
      environment fit, as well as theoretical notions related to individuating
      information, to develop a model, the political affiliation model (PAM), which
      describes the implications of political affiliation and political similarity for
      employment decisions. We set forth a number of propositions based on PAM, to spur
      future research in the organizational sciences for a timely topic which has
      received little attention. (PsycINFO Database Record

PMID- 28447828
TI  - Gender differences in depression in representative national samples: Meta
      analyses of diagnoses and symptoms.
AB  - In 2 meta-analyses on gender differences in depression in nationally
      representative samples, we advance previous work by including studies of
      depression diagnoses and symptoms to (a) estimate the magnitude of the gender
      difference in depression across a wide array of nations and ages; (b) use a
      developmental perspective to elucidate patterns of gender differences across the
      life span; and (c) incorporate additional theory-driven moderators (e.g., gender
      equity). For major depression diagnoses and depression symptoms, respectively, we
      meta-analyzed data from 65 and 95 articles and their corresponding national data
      sets, representing data from 1,716,195 and 1,922,064 people in over 90 different
      nations. Overall, odds ratio (OR) = 1.95, 95% confidence interval (CI) [1.88,
      2.03], and d = 0.27 [0.26, 0.29]. Age was the strongest predictor of effect size.
      The gender difference for diagnoses emerged earlier than previously thought, with
      OR = 2.37 at age 12. For both meta-analyses, the gender difference peaked in
      adolescence (OR = 3.02 for ages 13-15, and d = 0.47 for age 16) but then declined
      and remained stable in adulthood. Cross-national analyses indicated that larger
      gender differences were found in nations with greater gender equity, for major
      depression, but not depression symptoms. The gender difference in depression
      represents a health disparity, especially in adolescence, yet the magnitude of
      the difference indicates that depression in men should not be overlooked.
      (PsycINFO Database Record

PMID- 28447833
TI  - Ten-year trajectories of stressors and resources at work: Cumulative and chronic
      effects on health and well-being.
AB  - Employing 5 waves of measurement over a period of 10 years, we explored the
      effects of exposure to constellations of conditions at work on physical and
      psychological strain, estimating the history of exposure over time. Specifically,
      we first tested if the 4 constellations postulated by the job demand-control
      (JDC) model, extended to include social stressors, could be identified
      empirically over time through a person-centered analysis. Second, we tested 2
      specific effects of the history of exposure on physical and psychological strain:
      cumulative effects (i.e., history of exposure predicting strain) and chronic
      effects (i.e., history of exposure being associated with reduced reversibility in
      strain). Data were collected from 483 respondents who were at the end of their
      vocational training. The results supported the hypotheses, in that not all JDC
      constellations could be empirically identified, the majority of participants was
      in rather favorable constellations, and the differences between constellations,
      in terms of levels of demands and control, were more subtle than suggested by
      theoretically predefined constellations. Because the linear and quadratic
      solutions were largely comparable, we decided to adopt the linear ones. The
      expected cumulative and chronic effects were mostly confirmed: Unfavorable JDC
      constellations were associated with poorer health and well-being than favorable
      ones, when controlling for the initial level of the respective outcome variable,
      demographic variables, and for cumulative private stressors (cumulative effects).
      These differences largely remained after further adjustments for current
      conditions at work (chronic effects). (PsycINFO Database Record

PMID- 28447834
TI  - Perspectives of low-income chronically ill patients on complex care management.
AB  - INTRODUCTION: Low-income, chronically ill adults disproportionately experience
      poor health outcomes despite increased health care use and costs. Complex care
      management (CCM) programs are an innovative approach to improving outcomes for
      these patients, but little is known about the patients' experiences in CCM
      programs in safety net primary care settings. METHOD: The authors conducted
      semistructured interviews with 13 CCM participants in a safety net primary care
      clinic to explore their perceptions of their health and their experiences with
      CCM. Interviews were recorded, transcribed, independently coded, and analyzed
      through an iterative process using grounded theory methodology to identify themes
      in the participants' experiences. RESULTS: From our interviews, 3 themes emerged
      (a) participants mourned the loss of physical function and social well-being as a
      result of poor health; (b) participants reported increased health-related
      motivation due to relationships with the care team; and (c) participants
      experienced a newfound sense of control as a result of improved care navigation
      and self-management. DISCUSSION: Complex care management improved health-related
      motivation and provided a renewed sense of control for study participants, who
      were experiencing the loss of physical function and social well-being due to
      their chronic diseases. These findings support the importance of relationship
      centered care models in programs for low-income, chronically ill patients. Future
      research should focus on identifying and spreading best practices that
      effectively empower patients to feel more in control of their health. (PsycINFO
      Database Record

PMID- 28447835
TI  - It doesn't hurt to ask: Question-asking increases liking.
AB  - Conversation is a fundamental human experience that is necessary to pursue
      intrapersonal and interpersonal goals across myriad contexts, relationships, and
      modes of communication. In the current research, we isolate the role of an
      understudied conversational behavior: question-asking. Across 3 studies of live
      dyadic conversations, we identify a robust and consistent relationship between
      question-asking and liking: people who ask more questions, particularly follow-up
      questions, are better liked by their conversation partners. When people are
      instructed to ask more questions, they are perceived as higher in responsiveness,
      an interpersonal construct that captures listening, understanding, validation,
      and care. We measure responsiveness with an attitudinal measure from previous
      research as well as a novel behavioral measure: the number of follow-up questions
      one asks. In both cases, responsiveness explains the effect of question-asking on
      liking. In addition to analyzing live get-to-know-you conversations online, we
      also studied face-to-face speed-dating conversations. We trained a natural
      language processing algorithm as a "follow-up question detector" that we applied
      to our speed-dating data (and can be applied to any text data to more deeply
      understand question-asking dynamics). The follow-up question rate established by
      the algorithm showed that speed daters who ask more follow-up questions during
      their dates are more likely to elicit agreement for second dates from their
      partners, a behavioral indicator of liking. We also find that, despite the
      persistent and beneficial effects of asking questions, people do not anticipate
      that question-asking increases interpersonal liking. (PsycINFO Database Record

PMID- 28447836
TI  - The Goldilocks contract: The synergistic benefits of combining structure and
      autonomy for persistence, creativity, and cooperation.
AB  - Contracts are commonly used to regulate a wide range of interactions and
      relationships. Yet relying on contracts as a mechanism of control often comes at
      a cost to motivation. Integrating theoretical perspectives from psychology,
      economics, and organizational theory, we explore this control-motivation dilemma
      inherent in contracts and present the Contract-Autonomy-Motivation-Performance
      Structure (CAMPS) model, which highlights the synergistic benefits of combining
      structure and autonomy. The model proposes that subtle reductions in the
      specificity of a contract's language can boost autonomy, which increases
      intrinsic motivation and improves a range of desirable behaviors. Nine field and
      laboratory experiments found that less specific contracts increased task
      persistence, creativity, and cooperation, both immediately and longitudinally,
      because they boosted autonomy and intrinsic motivation. These positive effects,
      however, only occurred when contracts provided sufficient structure. Furthermore,
      the effects were limited to control-oriented clauses (i.e., legal clauses), and
      did not extend to coordination-oriented clauses (i.e., technical clauses). That
      is, there were synergistic benefits when a contract served as a scaffold that
      combined structure with general clauses. Overall, the current model and
      experiments identify a low-cost solution to the common problem of regulating
      social relationships: finding the right amount of contract specificity promotes
      desirable outcomes, including behaviors that are notoriously difficult to
      contract. The CAMPS model and the current set of empirical findings explain why,
      when, and how contracts can be used as an effective motivational tool. (PsycINFO
      Database Record

PMID- 28447837
TI  - The state of social and personality science: Rotten to the core, not so bad,
      getting better, or getting worse?
AB  - The scientific quality of social and personality psychology has been debated at
      great length in recent years. Despite research on the prevalence of Questionable
      Research Practices (QRPs) and the replicability of particular findings, the
      impact of the current discussion on research practices is unknown. The current
      studies examine whether and how practices have changed, if at all, over the last
      10 years. In Study 1, we surveyed 1,166 social and personality psychologists
      about how the current debate has affected their perceptions of their own and the
      field's research practices. In Study 2, we coded the research practices and
      critical test statistics from social and personality psychology articles
      published in 2003-2004 and 2013-2014. Together, these studies suggest that (a)
      perceptions of the current state of the field are more pessimistic than
      optimistic; (b) the discussion has increased researchers' intentions to avoid
      QRPs and adopt proposed best practices, (c) the estimated replicability of
      research published in 2003-2004 may not be as bad as many feared, and (d)
      research published in 2013-2014 shows some improvement over research published in
      2003-2004, a result that suggests the field is evolving in a positive direction.
      (PsycINFO Database Record

PMID- 28447838
TI  - In defense of commitment: The curative power of violated expectations.
AB  - A new model of commitment defense in romantic relationships is proposed. It
      assumes that relationships afford a central resource for affirming meaning and
      purpose in the world. Consequently, violating expectations about the world
      outside the relationship can precipitate commitment defense inside the
      relationship. A meta-analysis of 5 experiments, 2 follow-up correlational
      studies, and a longitudinal study of the transition to first parenthood supported
      the model. Experimentally violating conventional expectations about the world
      (e.g., "hard work pays off") motivated less satisfied people to defensively
      affirm their commitment. Similarly, when becoming a parent naturalistically
      violated culturally conditioned gendered expectations about the division of
      household labor, less satisfied new mothers and fathers defensively affirmed
      their commitment from pre-to-post baby. The findings suggest that violating
      expected associations in the world outside the relationship motivates vulnerable
      people to set relationship their relationship right, thereby affirming expected
      associations in the relationship in the face of an unexpected world. (PsycINFO
      Database Record

PMID- 28447839
TI  - The Whorfian time warp: Representing duration through the language hourglass.
AB  - How do humans construct their mental representations of the passage of time? The
      universalist account claims that abstract concepts like time are universal across
      humans. In contrast, the linguistic relativity hypothesis holds that speakers of
      different languages represent duration differently. The precise impact of
      language on duration representation is, however, unknown. Here, we show that
      language can have a powerful role in transforming humans' psychophysical
      experience of time. Contrary to the universalist account, we found language
      specific interference in a duration reproduction task, where stimulus duration
      conflicted with its physical growth. When reproducing duration, Swedish speakers
      were misled by stimulus length, and Spanish speakers were misled by stimulus
      size/quantity. These patterns conform to preferred expressions of duration
      magnitude in these languages (Swedish: long/short time; Spanish: much/small
      time). Critically, Spanish-Swedish bilinguals performing the task in both
      languages showed different interference depending on language context. Such
      shifting behavior within the same individual reveals hitherto undocumented levels
      of flexibility in time representation. Finally, contrary to the linguistic
      relativity hypothesis, language interference was confined to difficult
      discriminations (i.e., when stimuli varied only subtly in duration and growth),
      and was eliminated when linguistic cues were removed from the task. These results
      reveal the malleable nature of human time representation as part of a highly
      adaptive information processing system. (PsycINFO Database Record

PMID- 28447840
TI  - The rational status of quantum cognition.
AB  - Classic probability theory (CPT) is generally considered the rational way to make
      inferences, but there have been some empirical findings showing a divergence
      between reasoning and the principles of classical probability theory (CPT),
      inviting the conclusion that humans are irrational. Perhaps the most famous of
      these findings is the conjunction fallacy (CF). Recently, the CF has been shown
      consistent with the principles of an alternative probabilistic framework, quantum
      probability theory (QPT). Does this imply that QPT is irrational or does QPT
      provide an alternative interpretation of rationality? Our presentation consists
      of 3 parts. First, we examine the putative rational status of QPT using the same
      argument as used to establish the rationality of CPT, the Dutch Book (DB)
      argument, according to which reasoners should not commit to bets guaranteeing a
      loss. We prove the rational status of QPT by formulating it as a particular case
      of an extended form of CPT, with separate probability spaces produced by changing
      context. Second, we empirically examine the key requirement for whether a CF can
      be rational or not; the results show that participants indeed behave rationally,
      at least relative to the representations they employ. Finally, we consider
      whether the conditions for the CF to be rational are applicable in the outside
      (nonmental) world. Our discussion provides a general and alternative perspective
      for rational probabilistic inference, based on the idea that contextuality
      requires either reasoning in separate CPT probability spaces or reasoning with
      QPT principles. (PsycINFO Database Record

PMID- 28447841
TI  - Examining depletion theories under conditions of within-task transfer.
AB  - In everyday life, mental fatigue can be detrimental across many domains including
      driving, learning, and working. Given the importance of understanding and
      accounting for the deleterious effects of mental fatigue on behavior, a growing
      body of literature has studied the role of motivational and executive control
      processes in mental fatigue. In typical laboratory paradigms, participants
      complete a task that places demand on these self-control processes and are later
      given a subsequent task. Generally speaking, decrements to subsequent task
      performance are taken as evidence that the initial task created mental fatigue
      through the continued engagement of motivational and executive functions. Several
      models have been developed to account for negative transfer resulting from this
      "ego depletion." In the current study, we provide a brief literature review,
      specify current theoretical approaches to ego-depletion, and report an empirical
      test of current models of depletion. Across 4 experiments we found minimal
      evidence for executive control depletion along with strong evidence for
      motivation mediated ego depletion. (PsycINFO Database Record

PMID- 28447842
TI  - Cognitive coupling during reading.
AB  - We hypothesize that cognitively engaged readers dynamically adjust their reading
      times with respect to text complexity (i.e., reading times should increase for
      difficult sections and decrease for easier ones) and failure to do so should
      impair comprehension. This hypothesis is consistent with theories of text
      comprehension but has surprisingly been untested. We tested this hypothesis by
      analyzing 4 datasets in which participants (N = 484) read expository texts using
      a self-paced reading paradigm. Participants self-reported mind wandering in
      response to pseudorandom thought-probes during reading and completed
      comprehension assessments after reading. We computed two measures of cognitive
      coupling by regressing each participant's paragraph-level reading times on two
      measures of text complexity: Flesch-Kincaid Grade Level and Word Concreteness
      scores. The two coupling measures yielded convergent findings: coupling was a
      negative predictor of mind wandering and a positive predictor of both text- and
      inference-level comprehension. Goodness-of-fit, measured with Akaike information
      criterion, also improved after adding coupling to the reading-time only models.
      Furthermore, cognitive coupling mediated the relationship between mind wandering
      and comprehension, supporting the hypothesis that mind wandering engenders a
      decoupling of attention from external stimuli. (PsycINFO Database Record

PMID- 28447843
TI  - Seeing "what" through "why": Evidence from probing the causal structure of
      hierarchical motion.
AB  - Although our world is hierarchically organized, the perception, attention, and
      memory of hierarchical structures remain largely unknown. The current study shows
      how a hierarchical motion representation enhances the inference of an object's
      position in a dynamic display. The motion hierarchy is formed as an acyclic tree
      in which each node represents a distinctive motion component. Each individual
      object is instantiated as a node in the tree. In a position inference task,
      participants were asked to infer the position of a target object, given how it
      moved jointly with other objects. The results showed that the inference is
      supported by the context formed by nontarget objects. More importantly, this
      contextual effect is (a) structured, with stronger support from objects forming a
      hierarchical tree than from those moving independently; (b) degreed, with
      stronger support from objects closer to the target in the motion tree; and (c)
      directed, with stronger support from the target's ancestor nodes than from its
      descendent nodes. Computational modeling results further indicated that the
      contextual effect cannot be explained by correlated and contingent movements
      without an explicit causal representation of the motion hierarchy. Together,
      these studies suggest that human vision is a type of intelligence, which sees
      what are in the dynamic displays by recovering why and how they are generated.
      (PsycINFO Database Record

PMID- 28447844
TI  - Frontal theta band oscillations predict error correction and posterror slowing in
      typing.
AB  - Performance errors are associated with robust behavioral and
      electroencephalography (EEG) effects. However, there is a debate about the nature
      of the relationship between these effects and implicit versus explicit error
      awareness. Our aim was to study the relationship between error related
      electrophysiological effects, such as spectral perturbations in fronto-medial
      theta band oscillations (FMT), and error awareness in typing. Typing has an
      advantage as an experimental paradigm in that detected errors are quickly and
      habitually signaled by the participant using backspace, allowing separation of
      detected from undetected errors without interruption in behavior. Typing is
      thought to be controlled hierarchically via inner and outer loops, which rely on
      different sources for error detection. Touch-typist participants were asked to
      copy-type 100 sentences as EEG was recorded in the absence of visual feedback.
      Continuous EEG data were analyzed using independent component analysis (ICA).
      Time-frequency and ERP analyses were applied to emergent independent components.
      The results show that single-trial FMT parameters and error related negativity
      (ERN) amplitude predict overt, adaptive posterror actions such as error
      correction via backspace; and, posterror slowing, reflecting implicit error
      awareness. In addition, we found that those uncorrected errors which were slowed
      down the most were also the ones associated with a high level of FMT activity.
      Our results as a whole show that FMT are related to neural mechanisms involved in
      explicit awareness of errors, and input from inner loop is sufficient for error
      correction in typing. (PsycINFO Database Record

PMID- 28447845
TI  - Time course of motor affordances evoked by pictured objects and words.
AB  - Correspondence effects based on the relationship between the left/right position
      of a pictured object's handle and the hand used to make a response, or on the
      size of the object and the nature of a grip response (power/precision), have been
      attributed to motor affordances evoked by the object. Effects of this nature,
      however, are readily explained by the similarity in the abstract spatial coding
      of the features that define the stimulus and response, without recourse to object
      based affordances. We propose that in the task context of making reach-and-grasp
      actions, pictured objects may evoke genuine, limb-specific action constituents.
      We demonstrate that when subjects make reach-and-grasp responses, there is a
      qualitative difference in the time course of correspondence effects induced by
      pictures of objects versus the names of those objects. For word primes, this time
      course was consistent with the abstract spatial coding account, in which effects
      should emerge slowly and become apparent only among longer response times. In
      contrast, correspondence effects attributable to object primes were apparent even
      among the shortest response times and were invariant across the entire response
      time distribution. Using rotated versions of object primes provided evidence for
      a short-lived competition between canonical and depicted orientations of an
      object with respect to eliciting components of associated actions. These results
      suggest that under task conditions requiring reach-and-grasp responses, pictured
      objects rapidly trigger constituents of real-world actions. (PsycINFO Database
      Record

PMID- 28447846
TI  - Attentional state modulates the effect of an irrelevant stimulus dimension on
      perception.
AB  - Covariations of acoustic features provide redundancy in rapidly changing
      soundscapes: Hearing one feature enables a listener to infer another if these 2
      features normally covary. However, it is unknown whether situational demands
      affect the degree to which covariations influence perceptual inferences. We
      exploited a perceptual interdependency between modulation rate and frequency and
      examined, in 6 experiments, whether challenging situations would alter the degree
      to which people rely on frequency information to make decisions about modulation
      rate. Participants listened to amplitude-modulated (AM) sounds with modulation
      rates (~5 Hz) either decreasing or increasing over time and identified the
      direction of the rate change. Participants were instructed to ignore carrier
      frequency, which either decreased or increased (~1,300 Hz) over time. We observed
      that participants were more likely to perceive the modulation rate as slowing
      down when frequency decreased and as speeding up when frequency increased (AM
      rate change illusion). The magnitude of the illusion increased when uninformative
      cues (compared with informative cues) prohibited regulation of attention to
      sounds, and under distraction introduced by a concurrent visual motion-tracking
      task. The evidence suggests that the attentional state affects how strongly
      people rely on featural covariations to make perceptual inferences. (PsycINFO
      Database Record

PMID- 28447847
TI  - The speed of voluntary and priority-driven shifts of visual attention.
AB  - The question how fast spatial attention moves between different visual objects
      remains debated. We used electrophysiological measures to determine the speed of
      voluntary and visually guided shifts of attention. Participants shifted attention
      from a known benchmark object (T1) to a benchmark-defined target object (T2) in
      tasks where these shifts had to be controlled endogenously and tasks where they
      could be guided by visible stimulus attributes (target features or arrow cues).
      To track the speed of these attention shifts, we measured event-related potential
      (ERP) markers of attentional object selection (N2pc components). The N2pc to T1
      emerged earlier than the N2pc to T2, confirming the presence of serial attention
      shifts. N2pc onset differences between T1 and T2 revealed that shifts guided by
      target features were triggered within 50 ms, whereas voluntary movements of
      attention took substantially longer (150 ms). Attention shifts signaled by arrow
      cues were initiated within about 100 ms. Results show that genuinely voluntary
      shifts of attention are slower than shifts that are guided by cues or target
      features, but can still be initiated more rapidly than has previously been
      assumed. They also demonstrate that EEG markers can track different types of
      serial attentional selection processes with high temporal precision. (PsycINFO
      Database Record

PMID- 28447848
TI  - Spatial biases in motion extrapolation for manual interception.
AB  - The exact mechanisms by which humans control the manual interception of moving
      targets are currently unknown. Here, the authors explored the behaviors
      associated with the spatial control for manual interception. The examined task
      required controlling a cursor to intercept moving targets on a touch screen. They
      explored the effects of target motion direction, curvature and occlusion on
      manual interception. They observed occlusion-dependent spatial errors and arrival
      times for curved and diagonal trajectories (larger errors and earlier arrival of
      the finger at its final position with longer occlusion). These effects were
      particularly apparent for targets moving away from screen center at interception
      due to curve. In a follow-up experiment, the authors showed that the outward
      curve effects on spatial errors were absent because the associated trajectories
      appears to move toward positions that participants could expect the target to
      never reach. Their analyses also revealed occlusion-dependent spatial errors for
      diagonal trajectories, which is the well-known angle-of-approach effect. Follow
      up experiments demonstrated that this effect was not due to the central initial
      cursor position acting as a visual reference point or the initial ocular pursuit.
      Most importantly, the angle-of-approach effect persisted in a judgment task. The
      authors thus concluded that this effect does not stem from online information
      based modulations of movement speed, but from target information used to control
      aiming (i.e., movement direction). Moreover, processing for diagonal target
      motion appears to be biased toward straight downward. (PsycINFO Database Record

PMID- 28447849
TI  - A large-scale horizontal-vertical illusion produced with small objects separated
      in depth.
AB  - We conducted two experiments (total N = 81) to investigate the basis for the
      large-scale horizontal-vertical illusion (HVI), which is typically measured as
      15%-20% and has previously been linked to the presence of a ground plane. In a
      preliminary experiment, vertical rods of similar angular extents that were either
      large (4.5-7.5 m) and far, or small (0.9-1.5 m) and near, were matched to
      horizontal extents in a virtual environment by adjustment of horizontal gaps or
      rods. Large/far objects showed a larger HVI (~13%) than did small objects (~7%),
      as has been shown before, but the horizontal gap normally used to measure the
      large-scale HVI was not the source of the larger bias. In the second experiment,
      we found that simply separating the comparison rod in depth from the vertical rod
      (thus forcing an evaluation of size at a distance) was sufficient to produce a
      large HVI (17%), even with small rods. The results are interpreted in light of
      evidence that the large-scale HVI is dependent on ground plane orientation and
      may be related to differential angular expansion in the visual coding of
      elevation and azimuth. (PsycINFO Database Record

PMID- 28447851
TI  - "Understanding the role of speech production in reading: Evidence for a print-to
      speech neural network using graphical analysis": Correction to Cummine et al.
      (2016).
AB  - : Reports an error in "Understanding the role of speech production in reading:
      Evidence for a print-to-speech neural network using graphical analysis" by
      Jacqueline Cummine, Ivor Cribben, Connie Luu, Esther Kim, Reyhaneh Bahktiari,
      George Georgiou and Carol A. Boliek (Neuropsychology, 2016[May], Vol 30[4], 385
      397). In the article, the fifth author's name [Bakhtiari] was misspelled. The
      online version of this article has been corrected. (The following abstract of the
      original article appeared in record 2015-49069-001.) Objective: The neural
      circuitry associated with language processing is complex and dynamic. Graphical
      models are useful for studying complex neural networks as this method provides
      information about unique connectivity between regions within the context of the
      entire network of interest. Here, the authors explored the neural networks during
      covert reading to determine the role of feedforward and feedback loops in covert
      speech production. METHOD: Brain activity of skilled adult readers was assessed
      in real word and pseudoword reading tasks with functional MRI (fMRI). RESULTS:
      The authors provide evidence for activity coherence in the feedforward system
      (inferior frontal gyrus-supplementary motor area) during real word reading and in
      the feedback system (supramarginal gyrus-precentral gyrus) during pseudoword
      reading. Graphical models provided evidence of an extensive, highly connected,
      neural network when individuals read real words that relied on coordination of
      the feedforward system. In contrast, when individuals read pseudowords the
      authors found a limited/restricted network that relied on coordination of the
      feedback system. CONCLUSION: Together, these results underscore the importance of
      considering multiple pathways and articulatory loops during language tasks and
      provide evidence for a print-to-speech neural network. (PsycINFO Database Record

PMID- 28447850
TI  - Links between temporal acuity and multisensory integration across life span.
AB  - The temporal relationship between individual pieces of information from the
      different sensory modalities is one of the stronger cues to integrate such
      information into a unified perceptual gestalt, conveying numerous perceptual and
      behavioral advantages. Temporal acuity, however, varies greatly over the life
      span. It has previously been hypothesized that changes in temporal acuity in both
      development and healthy aging may thus play a key role in integrative abilities.
      This study tested the temporal acuity of 138 individuals ranging in age from 5 to
      80. Temporal acuity and multisensory integration abilities were tested both
      within and across modalities (audition and vision) with simultaneity judgment and
      temporal order judgment tasks. We observed that temporal acuity, both within and
      across modalities, improved throughout development into adulthood and
      subsequently declined with healthy aging, as did the ability to integrate
      multisensory speech information. Of importance, throughout development, temporal
      acuity of simple stimuli (i.e., flashes and beeps) predicted individuals'
      abilities to integrate more complex speech information. However, in the aging
      population, although temporal acuity declined with healthy aging and was
      accompanied by declines in integrative abilities, temporal acuity was not able to
      predict integration at the individual level. Together, these results suggest that
      the impact of temporal acuity on multisensory integration varies throughout the
      life span. Although the maturation of temporal acuity drives the rise of
      multisensory integrative abilities during development, it is unable to account
      for changes in integrative abilities in healthy aging. The differential
      relationships between age, temporal acuity, and multisensory integration suggest
      an important role for experience in these processes. (PsycINFO Database Record

PMID- 28447852
TI  - Pressure Ulcers Prevalence in the Acute Care Setting: A Systematic Review, 2000
      2015.
AB  - Little is known about the prevalence of pressure ulcer (PrU) in acute care
      settings. The aim of this study is to determine the prevalence rate of PrU in
      acute care settings and to assess the methodological quality of the reviewed
      publications. The Cumulative Index to Nursing and Allied Health Literature,
      British Nursing Index, MEDLINE, and Cochrane Database of Systematic Reviews were
      searched using the keywords pressure ulcer or decubitus ulcer or bed sore or
      pressure sore or pressure injury, with prevalence and acute care, for studies
      published between January 2000 and December 2015. Nineteen publications met our
      criteria. These reported a prevalence range of between 7.8% and 54% for those
      using European Pressure Ulcer Advisory Panel methodology, 6% and 22% for those
      using National Pressure Ulcer Advisory Panel methodology, and 4.94% for the study
      that employed the Torrance system. The likely worldwide PrU prevalence rate range
      in acute care settings is between 6% and 18.5%. Prevalence rate varies between
      studies depending on the methodology of data collection. Moreover, the
      methodological quality of the included studies in the review was variable;
      therefore, it was difficult to compare the prevalence rate between the studies,
      settings, and countries.

PMID- 28447853
TI  - Finding Balance: Standardizing Practice Is Corseting Physician Judgement.

PMID- 28447854
TI  - Healthy diet: Health impact, prevalence, correlates, and interventions.
AB  - OBJECTIVE: To discuss healthy diet from a psychological perspective by
      considering definitions of healthy diet in terms of consumer understanding; the
      health effects of specific dietary elements in terms of overweight and (chronic)
      illness; the prevalence of healthy diet; the psychological and environmental
      determinants of healthy diet; and the psychological interventions that have been
      designed to promote healthy diet. DESIGN: A systematic review of the
      psychological literature on healthy diet. RESULTS: Our findings suggest that
      consumers have a relatively poor understanding of a healthy diet. The literature
      also demonstrates that there is poor evidence on the health protective effects of
      single foods or nutrients. We further show that low SES is the single consistent
      risk factor for not adhering to a healthy diet. Our review of the literature on
      determinants demonstrates that intentions, habits, self-regulatory skills, and
      the social and physical environment are the most important determinants of a
      healthy diet, which are in turn amenable to change by intervention strategies
      with varying levels of effectiveness. Educational interventions generally show a
      limited effect on practising a healthy diet whereas interventions targeting
      habitual behaviour and/or the physical environment seem more promising.
      CONCLUSIONS: In view of the large number of people who are concerned about their
      diets and make attempts to change their dietary patterns, we conclude that it is
      crucial to gain a better understanding of both the automatic and environmental
      influences that are responsible for people not acting upon their good intentions
      for diet change.

PMID- 28447855
TI  - The Arterial Anatomy of the Deltoid Ligament: A Cadaveric Study.
AB  - BACKGROUND: There is an increasing interest in the operative treatment of deltoid
      ligament disruption in the setting of chronic ankle instability. Understanding
      the vascular anatomy of the deltoid complex is beneficial when considering
      operative procedures on the medial ankle and may provide insight into factors
      that lead to chronic deltoid insufficiency and ankle instability. METHODS: Thirty
      two pairs of cadaveric specimens (64 total legs) were amputated below the knee,
      and the tibialis anterior, tibialis posterior, and peroneal arteries were
      injected with India ink and Ward's blue latex. Specimens then underwent chemical
      debridement to identify the vascular supply to the deltoid ligament. A subset of
      specimens also underwent intraosseous debridement using the modified Spalteholz
      technique. RESULTS: The vascular supply to the deltoid ligament was clearly
      visualized in 60 (93.8%) specimens. Fifty-eight specimens (96.7%) had arterial
      supply with an origin from the medial tarsal artery, 57 specimens (95%) had
      supply from the tibialis posterior artery, and 23 (38.3%) specimens had supply
      from the tibialis anterior artery. All specimens had at least 1 location of
      intraosseous vascular supply, either at the medial malleolus or medial talus.
      CONCLUSION: There were 3 separate extraosseous sources and 2 intraosseous sources
      of vascular supply to the deltoid ligament. CLINICAL RELEVANCE: Knowledge of the
      vascular supply may aid in identifying factors that predispose a subset of
      patients with medial ankle sprains to failure of conservative treatment, as well
      as provide useful anatomic information when considering operative treatment for
      chronic ankle instability.

PMID- 28447856
TI  - Evaluation of the Nutritional Changes Caused by Huanglongbing (HLB) to Citrus
      Plants Using Laser-Induced Breakdown Spectroscopy.
AB  - Huanglongbing (HLB) is the most recent and destructive bacterial disease of
      citrus and has no cure yet. A promising alternative to conventional methods is to
      use laser-induced breakdown spectroscopy (LIBS), a multi-elemental analytical
      technique, to identify the nutritional changes provoked by the disease to the
      citrus leaves and associate the mineral composition profile with its health
      status. The leaves were collected from adult citrus trees and identified by
      visual inspection as healthy, HLB-symptomatic, and HLB-asymptomatic. Laser
      induced breakdown spectroscopy measurements were done in fresh leaves without
      sample preparation. Nutritional variations were evaluated using statistical
      tools, such as Student's t-test and analysis of variance applied to LIBS spectra,
      and the largest were found for Ca, Mg, and K. Considering the nutritional profile
      changes, a classifier induced by classification via regression combined with
      partial least squares regression was built resulting in an accuracy of 73% for
      distinguishing the three categories of leaves.

PMID- 28447857
TI  - CpG-specific methylation at rheumatoid arthritis diagnosis as a marker of
      treatment response.

PMID- 28447858
TI  - Risk prediction of hepatotoxicity in paracetamol poisoning.
AB  - CONTEXT: Paracetamol (acetaminophen) poisoning is the most common cause of acute
      liver failure in the developed world. A paracetamol treatment nomogram has been
      used for over four decades to help determine whether patients will develop
      hepatotoxicity without acetylcysteine treatment, and thus indicates those needing
      treatment. Despite this, a small proportion of patients still develop
      hepatotoxicity. More accurate risk predictors would be useful to increase the
      early detection of patients with the potential to develop hepatotoxicity despite
      acetylcysteine treatment. Similarly, there would be benefit in early
      identification of those with a low likelihood of developing hepatotoxicity, as
      this group may be safely treated with an abbreviated acetylcysteine regimen. AIM:
      To review the current literature related to risk prediction tools that can be
      used to identify patients at increased risk of hepatotoxicity. METHODS: A
      systematic literature review was conducted using the search terms: "paracetamol"
      OR "acetaminophen" AND "overdose" OR "toxicity" OR "risk prediction rules" OR
      "hepatotoxicity" OR "psi parameter" OR "multiplication product" OR "half-life" OR
      "prothrombin time" OR "AST/ALT (aspartate transaminase/alanine transaminase)" OR
      "dose" OR "biomarkers" OR "nomogram". The search was limited to human studies
      without language restrictions, of Medline (1946 to May 2016), PubMed and EMBASE.
      Original articles pertaining to the theme were identified from January 1974 to
      May 2016. Of the 13,975 articles identified, 60 were relevant to the review.
      Paracetamol treatment nomograms: Paracetamol treatment nomograms have been used
      for decades to help decide the need for acetylcysteine, but rarely used to
      determine the risk of hepatotoxicity with treatment. Reported paracetamol dose
      and concentration: A dose ingestion >12 g or serum paracetamol concentration
      above the treatment thresholds on the paracetamol nomogram are associated with a
      greater risk of hepatotoxicity. Paracetamol elimination half-life: Patients with
      more severe hepatotoxicity are more likely to have a longer paracetamol
      elimination half-life. While median elimination half-life increases in those
      developing hepatotoxicity, there is wide variation in half-life, making this an
      insensitive parameter to use as a negative risk prediction tool. Prothrombin time
      (PT): An initially normal PT is associated with a lower risk of developing
      hepatotoxicity, but cannot be used alone to identify patients not requiring
      acetylcysteine treatment. Hepatic aminotransferase activity: A normal ALT
      activity on presentation is associated with a high negative predictive value of
      hepatotoxicity following paracetamol-poisoning. Psi parameter: The psi parameter
      takes into account the time from ingestion, the serum paracetamol concentration
      and the time to initiation of acetylcysteine. A hepatotoxicity risk nomogram
      based on this parameter may be easier to use, but is limited to acute ingestions.
      Paracetamol-aminotransferase multiplication product: If a hepatotoxicity risk
      nomogram is not available, an alternate strategy may be to use the paracetamol
      aminotransferase product (<1500 low risk, 1500-10,000 low to moderate risk,
      >10,000 mg/L * IU/L high risk) to define liver injury risk. Serial blood tests
      can be performed if patients present prior to 8 h post-overdose for ultimate
      specificity, or a single blood test can be taken if presenting more than 8 h post
      overdose. Patients receiving acetylcysteine within 8 h of their overdose, with a
      product less than 10,000 mg/L * IU/L have a low likelihood of developing
      hepatotoxicity. Any clinical trials of intensified treatment (e.g., higher dose)
      to prevent fulminant hepatic failure might potentially use a product of >10,000
      mg/L * IU/L as a criterion for inclusion. The paracetamol-aminotransferase
      product <1500 mg/L * IU/L may also identify those suitable for an abbreviated
      acetylcysteine regimen. Newer biomarkers: These show promise in the early
      identification of patients with a higher risk of developing hepatic injury. Point
      of care devices measuring paracetamol adducts need further trials. CONCLUSIONS:
      Risk prediction tools can stratify those that are more likely to develop
      hepatotoxicity. Currently, the paracetamol-aminotransferase multiplication
      product may be such a tool. Novel biomarkers show promise but need further
      validation and greater clinical availability. These tools may help inform
      clinical trials on modified acetylcysteine regimens.

PMID- 28447860
TI  - Remote sensing of physiological signs using a machine vision system.
AB  - The aim of this work is to remotely measure heart rate (HR) and respiratory rate
      (RR) using a video camera from long range (> 50 m). The proposed system is based
      on imperceptible signals produced from blood circulation, including skin colour
      variations and head motion. As these signals are not visible to the naked eye and
      to preserve the signal strength in the video, we used an improved video
      magnification technique to enhance these invisible signals and detect the
      physiological activity within the subject. The software of the proposed system
      was built in a graphic user interface (GUI) environment to easily select a
      magnification system to use (colour or motion magnification) and measure the
      physiological signs independently. The measurements were performed on a set of 10
      healthy subjects equipped with a finger pulse oximeter and respiratory belt
      transducer that were used as reference methods. The experimental results were
      statistically analysed by using the Bland-Altman method, Pearson's correlation
      coefficient, Spearman correlation coefficient, mean absolute error, and root mean
      squared error. The proposed system achieved high correlation even in the presence
      of movement artefacts, different skin tones, lighting conditions and distance
      from the camera. With acceptable performance and low computational complexity,
      the proposed system is a suitable candidate for homecare applications, security
      applications and mobile health devices.

PMID- 28447859
TI  - Transgene Expression in Dogs After Liver-Directed Hydrodynamic Delivery of
      Sleeping Beauty Transposons Using Balloon Catheters.
AB  - The Sleeping Beauty transposon system has been extensively tested for integration
      of reporter and therapeutic genes in vitro and in vivo in mice. Dogs were used as
      a large animal model for human therapy and minimally invasive infusion of DNA
      solutions. DNA solutions were delivered into the entire liver or the left side of
      the liver using balloon catheters for temporary occlusion of venous outflow. A
      peak intravascular pressure between 80 and 140 mmHg supported sufficient DNA
      delivery in dog liver for detection of secretable reporter proteins. Secretable
      reporters allowed monitoring of the time course of gene products detectable in
      the circulation postinfusion. Canine secreted alkaline phosphatase reporter
      protein levels were measured in plasma, with expression detectable for up to 6
      weeks, while expression of canine erythropoietin was detectable for 7-10 days.
      All animals exhibited a transient increase in blood transaminases that normalized
      within 10 days; otherwise the treated animals were clinically normal. These
      results demonstrate the utility of a secreted reporter protein for real-time
      monitoring of gene expression in the liver in a large animal model but highlight
      the need for improved delivery in target tissues to support integration and long
      term expression of Sleeping Beauty transposons.

PMID- 28447861
TI  - Screening and early detection of oral cancer: current controversies.
AB  - Some evidence suggests that the early detection of oral cancer (OC) during
      surveillance might improve survival rates. In addition to this, interventions
      aimed at enhancing public awareness and knowledge of signs, symptoms and risk
      factors of OC are thought to decrease the burden of disease. Nevertheless, there
      is much controversy with regard to the cost-effectiveness of population-based
      strategies for OC screening. Here, we present and briefly discuss timely findings
      that have put under scrutiny the applicability of approaches targeted at the
      early identification of patients with OC.

PMID- 28447862
TI  - High-reliability microcontroller nerve stimulator for assistance in regional
      anaesthesia procedures.
AB  - In the last decades, the use of nerve stimulators to aid in regional anaesthesia
      has been shown to benefit the patient since it allows a better location of the
      nerve plexus, leading to correct positioning of the needle through which the
      anaesthetic is applied. However, most of the nerve stimulators available in the
      market for this purpose do not have the minimum recommended features for a good
      stimulator, and this can lead to risks to the patient. Thus, this study aims to
      develop an equipment, using embedded electronics, which meets all the
      characteristics, for a successful blockade. The system is made of modules for
      generation and overall control of the current pulse and the patient and user
      interfaces. The results show that the designed system fits into required
      specifications for a good and reliable nerve stimulator. Linearity proved
      satisfactory, ensuring accuracy in electrical current amplitude for a wide range
      of body impedances. Field tests have proven very successful. The
      anaesthesiologist that used the system reported that, in all cases, plexus
      blocking was achieved with higher quality, faster anaesthetic diffusion and
      without needed of an additional dose when compared with same procedure without
      the use of the device.

PMID- 28447863
TI  - Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P
      glycoprotein transport at the blood-brain barrier.
AB  - The blood-brain barrier is a microvascular network that (1) provides
      neuroprotection from metabolic and environmental toxins and (2) limits the
      delivery of therapeutics to the central nervous system (CNS). The ATP-binding
      cassette transporter P-glycoprotein contributes to the latter by actively pumping
      clinical substrates back into circulation before they can reach the brain
      parenchyma. Targeting P-glycoprotein has proven effective in increasing the
      delivery of therapeutics to their cerebral targets. We provide a novel mechanism
      to achieve this end in functioning, intact rat brain capillaries, whereby the
      bioactive phospholipid lysophosphatidic acid (LPA) and tricyclic antidepressant
      (TCA) amitriptyline reduce basal P-glycoprotein transport activity through a
      distinct lysophosphatidic acid 1 receptor-mediated signaling cascade that
      requires G-protein coupling, Src kinase, and ERK 1/2. Furthermore, we demonstrate
      the ability of LPA and TCA amitriptyline to decrease induced P-glycoprotein
      transport activity in a human SOD1 transgenic rat model of amyotrophic lateral
      sclerosis. This work may translate to new clinical strategies for increasing the
      cerebral penetration of therapeutics in patients suffering from CNS diseases
      marked by exacerbated pharmacoresistance.

PMID- 28447864
TI  - The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms
      - a review.
AB  - INTRODUCTION: Hyperandrogenism affects approximately 10-20% of women of
      reproductive age. Hyperandrogenic skin symptoms such as hirsutism, acne,
      seborrhea and alopecia are associated with significant quality of life and
      psychological impairment. Women with abnormalities in androgen metabolism may
      have accompanying anovulation and/or polycystic ovary syndrome (PCOS), both of
      which have reproductive and metabolic implications if left untreated. Cyproterone
      acetate (CPA), combined with ethinylestradiol (EE), is indicated for the
      treatment of moderate to severe acne related to androgen-sensitivity (with or
      without seborrhea) and/or hirsutism, in women of reproductive age. OBJECTIVE: To
      review the data on the efficacy and safety of CPA 2 mg/EE 35 MUg for the
      treatment of hyperandrogenic skin symptoms in women. METHODS: A non-systematic
      narrative review based on a literature search of the PubMed database. RESULTS:
      Seventy-eight studies were identified. The majority of sufficiently powered
      studies show a high efficacy of CPA 2 mg/EE 35 MUg in the treatment of severe
      acne and hirsutism. Studies show that therapeutic response in women with
      hirsutism requires a long-term approach and that hyperandrogenic skin symptoms in
      patients with PCOS are efficiently treated. Additional benefits include cycle
      control and, in some women, improvement in mood and perception of body image.
      Safety and tolerability data are summarized by the pharmacovigilance risk
      assessment committee (PRAC) of the European Medicine's Agency's (EMA).
      CONCLUSIONS: This review provides a comprehensive overview about the efficacy of
      CPA 2 mg/EE 35 MUg in the treatment of hyperandrogenic skin symptoms, thus
      allowing both health care professionals and women to balance the risks and
      benefits of treatment based on evidence.

PMID- 28447865
TI  - A versatile stretch sensor for measuring physiological movement using a centre
      loaded, end-supported load cell.
AB  - Acquisition of movement of some body parts can provide important physiological
      information. In clinical practice as well as for research purposes different
      types of sensors such as piezoelectric crystals, conductive rubber and optical
      displacement sensors are used for such measurements. Each of these sensors is
      associated with its problems. This paper discusses the use of a stretch sensor
      constructed using a small metal bar, approximately the size of a zipper slider
      that can be sewn into a fabric in the form of a belt. A combination of elastic,
      and Velcro material attached to the metal bar, provides a sensor that is capable
      of linear, steady state measurement as well as rapid response detecting slow and
      fast movement of the target. Incorporating the sensor in an elastic belt, allows
      measurement of physiological movements such as respiratory chest movements,
      abdominal and limb movements. This paper also discusses the potential use of the
      novel stretch sensor in measuring change in calf circumference during different
      manoeuvres, making it a useful assessment tool for calf venous function.

PMID- 28447866
TI  - Which Fecal Immunochemical Test Should I Choose?
AB  - OBJECTIVES: To summarize the fecal immunochemical tests (FITs) available in the
      United States, the 2014 pathology proficiency testing (PT) program FIT results,
      and the literature related to the test characteristics of FITs available in the
      United States to detect advanced adenomatous polyps (AAP) and/or colorectal
      cancer (CRC). METHODS: Detailed review of the Food and Drug Administration's
      Clinical Laboratory Improvement Amendments (CLIA) database of fecal occult blood
      tests, the 2014 FIT PT program results, and the literature related to FIT
      accuracy. RESULTS: A search of the CLIA database identified 65 FITs, with 26 FITs
      available for purchase in the United States. Thirteen of these FITs were
      evaluated on a regular basis by PT programs, with an overall sensitivity of 99.1%
      and specificity of 99.2% for samples spiked with hemoglobin. Automated FITs had
      better sensitivity and specificity than CLIA-waived FITs for detection of AAP and
      CRC in human studies using colonoscopy as the gold standard. CONCLUSION: Although
      many FITs are available in the United States, few have been tested in proficiency
      testing programs. Even fewer have data in humans on sensitivity and specificity
      for AAP or CRC. Our review indicates that automated FITs have the best test
      characteristics for AAP and CRC.

PMID- 28447867
TI  - Ginseng nanoparticles: a budding tool for cancer treatment.

PMID- 28447868
TI  - Doxorubicin-loaded liposomes: enhancing the oral bioavailability by modulation of
      physicochemical characteristics.
AB  - AIM: In this study, the effects of liposome characteristics on oral absorption of
      doxorubicin, as a hydrophilic low-permeability drug, were investigated. MATERIALS
      & METHODS: Different doxorubicin-loaded liposomes were prepared, characterized
      and orally administered to 18 groups of rats. Plasma concentrations of
      doxorubicin and its aglycone metabolite were measured, and Caco-2 uptake and
      transport of optimum liposomes were investigated. RESULTS: After studying
      different factors, a fourfold increase in oral bioavailability was achieved with
      the non-PEGylated, 120-nm-sized positively charged rigid liposomes (lipid to drug
      ratio = 10). The extent of drug's first-pass metabolism as well as endocytosis of
      nanoparticles were markedly affected by liposomal formulation. CONCLUSION: Oral
      absorption is highly dependent on liposomal properties, and optimum formulations
      are effective for low-permeability drugs.

PMID- 28447869
TI  - Mitigation of Discordant Rifampicin-Susceptibility Results Obtained by Xpert
      Mycobacterium tuberculosis/Rifampicin and Mycobacterium Growth Indicator Tube.
AB  - BACKGROUND: Simultaneous use of genotypic and phenotypic diagnostic tools for
      detection of rifampicin (RIF) susceptibility may yield discrepant results.
      OBJECTIVE: To measure the discordance between the RIF-susceptibility results by
      Xpert MTB/RIF and Mycobacterium Growth Indicator Tube (MGIT), to evaluate if
      application of both tests to the same sample affects the discrepancy, and to
      evaluate treatment outcome in patients with the discordant strains. DESIGN: Sputa
      from patients with tuberculosis managed in the penitentiary system of Azerbaijan
      during 2011-2015 were examined for RIF susceptibility using Xpert MTB/RIF and
      MGIT. Strains with discrepant results were sequenced. RESULTS: Of 532 patients
      included, 6.2% had discordant RIF-susceptibility results. No significant
      association of the discordant RIF-susceptibility results with application of both
      tests on one sample versus sequential samples was found. L511P mutation accounted
      significantly (p = 0.006) for the discrepancy among those RIF resistant on Xpert
      MTB/RIF, but sensitive on MGIT. No significant association was identified between
      the outcomes of treatment with the first- or second-line drugs and the presence
      of any mutation. CONCLUSION: The Xpert MTB/RIF and MGIT testing may be used in
      sequential sputum samples without increase in the RIF-susceptibility discordance
      rate. L511P mutation significantly accounts for discordant RIF-susceptibility
      results, but its clinical relevance may be low.

PMID- 28447870
TI  - Does Specialized Inpatient Rehabilitation Affect Whether or Not People with
      Traumatic Spinal Cord Injury Return Home?
AB  - Return to living at home is an important patient-reported outcome following
      traumatic spinal cord injury (tSCI). Specialized inpatient rehabilitation assists
      such patients in maximizing function and independence. Our project aim was to
      describe those patients receiving specialized rehabilitation after tSCI in
      Canada, and to determine if such rehabilitation improved the likelihood of
      returning home. This cohort study utilized data from the Rick Hansen Spinal Cord
      Injury Registry (RHSCIR) to identify patients with tSCI discharged from 1 of 18
      participating acute specialized spine facilities between 2011 and 2015 to either
      1 of 13 participating specialized rehabilitation facilities, or to another
      discharge destination. To determine if specialized rehabilitation affected
      likelihood of returning home, multiple logistic regressions and propensity score
      matchings were performed to account for age at injury, gender, neurological
      severity and level, acute length of stay (LOS), and region of residence. The chi2
      test was used to compare rate of return home between matched groups. Of the 1599
      patients included, 71% received specialized rehabilitation. Receiving specialized
      rehabilitation was a significant and strong predictor of return to home after
      controlling for covariates (adjusted odds ratio = 3.1; 95% confidence interval
      [CI], 1.6-5.9). The rate of return to home was significantly higher in the
      matched rehabilitation group than the no rehabilitation group (98% vs. 87%, p =
      0.0004). For the matched patients, an extra 11 patients returned home for every
      100 patients receiving specialized rehabilitation. However, effect of age on
      returning home requires further investigation. Improving access to specialized
      rehabilitation could potentially reduce discharges to nursing homes or other non
      home destinations.

PMID- 28447872
TI  - Nanophotosensitive drugs for light-based cancer therapy: what does the future
      hold?

PMID- 28447871
TI  - The Effects of Specialization and Sex on Anterior Y-Balance Performance in High
      School Athletes.
AB  - BACKGROUND: Sport specialization and movement asymmetry have been separately
      discussed as potential risk factors for lower extremity injury. Early
      specialization may lead to the development of movement asymmetries that can
      predispose an athlete to injury, but this has not been thoroughly examined.
      HYPOTHESIS: Athletes rated as specialized would exhibit greater between-limb
      anterior reach asymmetry and decreased anterior reach distance on the Y-balance
      test (YBT) as compared with nonspecialized high school athletes, and these
      differences would not be dependent on sex. STUDY DESIGN: Cross-sectional study.
      LEVEL OF EVIDENCE: Level 3. METHODS: Two hundred ninety-five athletes (117 male,
      178 female; mean age, 15.6 +/- 1.2 years) from 2 local high schools participating
      in basketball, soccer, volleyball, and tennis responded to a questionnaire
      regarding sport specialization status and performed trials of the YBT during
      preseason testing. Specialization was categorized according to 3 previously
      utilized specialization classification methods (single/multisport, 3-point scale,
      and 6-point scale), and interactions between specialization and sex with Y
      balance performance were calculated using 2-way analyses of variance. RESULTS:
      Single-sport male athletes displayed greater anterior reach asymmetry than other
      interaction groups. A consistent main effect was observed for sex, with men
      displaying greater anterior asymmetry and decreased anterior reach distance than
      women. However, the interaction effects of specialization and sex on anterior Y
      balance performance varied based on the classification method used. CONCLUSION:
      Single-sport male athletes displayed greater anterior reach asymmetry on the YBT
      than multisport and female athletes. Specialization classification method is
      important because the 6- and 3-point scales may not accurately identify balance
      abnormalities. Male athletes performed worse than female athletes on both of the
      Y-balance tasks. CLINICAL RELEVANCE: Clinicians should be aware that single-sport
      male athletes may display deficits in dynamic balance, potentially increasing
      their risk of injury.

PMID- 28447873
TI  - Employment Outcome Ten Years after Moderate to Severe Traumatic Brain Injury: A
      Prospective Cohort Study.
AB  - The objective of this prospective cohort study was to evaluate the probability of
      employment and predictors of employment in patients with moderate- to- severe
      traumatic brain injury (TBI) over 10-year follow-up. One hundred nine patients
      (18-67 years) were included with follow-up measurements 3, 6, 12, 18, 24, and 36
      months and 10 years post-TBI. Potential predictors of employment probability
      included patient characteristics, injury severity factors, functional outcome
      measured at discharge from the hospital with the Glasgow Outcome Scale (GOS),
      Barthel Index (BI), Functional Independence Measure (FIM), and the Functional
      Assessment Measure (FAM). Forty-eight patients (42%) completed the 10-year follow
      up. Three months post-TBI, 12% were employed, which gradually, but significantly,
      increased to 57% after 2-years follow-up (p < 0.001), followed by a significant
      decrease to 43% (p = 0.041) after 10 years. Ten years post-TBI, we found that
      employed persons had less-severe TBI, shorter length of hospital stay (LOS), and
      higher scores on the GOS, BI, FIM, and FAM at hospital discharge than unemployed
      persons. No significant differences in age, sex, educational level, living with
      partner/family or not, pre-injury employment, professional category, psychiatric
      symptoms, or discharge destination were found. Longitudinal multivariable
      analysis showed that time, pre-injury employment, FAM, and LOS were independent
      predictors of employment probability. We concluded that employment probability 10
      years after moderate or severe TBI is related to injury severity and pre-injury
      employment. Future studies on vocational rehabilitation should focus on
      modifiable factors and take into consideration the effects of national
      legislation and national labor market forces.

PMID- 28447874
TI  - Management of abdominal wall desmoid tumors.

PMID- 28447875
TI  - Introduction to the Special Issue on Locomotor Rehabilitation after Spinal Cord
      Injury.

PMID- 28447876
TI  - Intrinsic Mesenchymal Stem Cell Dysfunction in Diabetes Mellitus: Implications
      for Autologous Cell Therapy.
AB  - Mesenchymal stem cells derived from bone marrow (BM-MSCs) have multifunctional
      properties that have made them a promising therapeutic agent for many
      regenerative, anti-inflammatory, and autoimmune applications. Under chronic
      pathological conditions, however, BM-MSCs can become functionally compromised due
      to long-term exposure to changes in the systemic and localized stem cell niche
      microenvironments. In addition to the fact that functionally compromised BM-MSCs
      may be therapeutically ineffective, impairment of BM-MSCs is potentially a
      contributing factor to disease progression and development of comorbidities. For
      the purpose of this review, MSC-based therapies for treatment of nonhealing
      wounds in diabetic patients will be used as an example to demonstrate the effect
      that the diabetic host environment has on the regenerative capacity of endogenous
      BM-MSCs. This review will also discuss the mechanism by which the pathogenesis of
      diabetes mellitus leads to intrinsic dysfunction of the bone marrow stem cell
      niche that ultimately results in MSC failure and will highlight potential
      strategies for counteracting the functional decline of BM-MSCs.

PMID- 28447877
TI  - When Novel Rituals Lead to Intergroup Bias: Evidence From Economic Games and
      Neurophysiology.
AB  - Long-established rituals in preexisting cultural groups have been linked to the
      cultural evolution of group cooperation. We tested the prediction that novel
      rituals-arbitrary hand and body gestures enacted in a stereotypical and repeated
      fashion-can inculcate intergroup bias in newly formed groups. In four
      experiments, participants practiced novel rituals at home for 1 week (Experiments
      1, 2, and 4) or once in the lab (Experiment 3) and were divided into minimal in
      groups and out-groups. Our results offer mixed support for the hypothesis that
      novel rituals promote intergroup bias. Specifically, we found a modest effect for
      daily repeated rituals but a null effect for rituals enacted only once. These
      results suggest that novel rituals can inculcate bias, but only when certain
      features are present: Rituals must be sufficiently elaborate and repeated to lead
      to bias. Taken together, our results offer modest support that novel rituals can
      promote intergroup bias.

PMID- 28447878
TI  - Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery
      systems via dual tackling of its solubility and intestinal permeability.
AB  - OBJECTIVE: The aim of the current investigation was at enhancing the oral
      biopharmaceutical behavior; solubility and intestinal permeability of amisulpride
      (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L
      SNEDDS) containing bioenhancing excipients. METHODS: The components of L-SNEDDS
      were identified via solubility studies and emulsification efficiency tests, and
      ternary phase diagrams were constructed to identify the efficient self
      emulsification regions. The formulated systems were assessed for their
      thermodynamic stability, globule size, self-emulsification time, optical clarity
      and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique
      was adopted for uncovering the permeability enhancing effect of the formulated
      systems. RESULTS: The optimum formulations were composed of different ratios of
      CapryolTM 90 as an oil phase, Cremophor(r) RH40 as a surfactant, and
      Transcutol(r) HP as a co-surfactant. All tested formulations were
      thermodynamically stable with globule sizes ranging from 13.74 to 29.19 nm and
      emulsification time not exceeding 1 min, indicating the formation of homogenous
      stable nanoemulsions. In vitro drug release showed significant enhancement from L
      SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS
      showed significantly higher intestinal permeation compared to plain drug solution
      with nearly 1.6-2.9 folds increase in the apparent permeability coefficient as
      demonstrated by the ex vivo studies. CONCLUSIONS: The present study proved that
      AMS could be successfully incorporated into L-SNEDDS for improved dissolution and
      intestinal permeation leading to enhanced oral delivery.

PMID- 28447879
TI  - The lived experience of caregivers of persons with heart failure: A
      phenomenological study.
AB  - BACKGROUND: Heart failure (HF) patients need to follow a strict pharmacological
      and nonpharmacological regimen in order to counteract the burden of the disease,
      and informal caregivers are an important resource for HF patients in managing and
      coping with their disease. Few studies have examined the lived experience of
      these caregivers with a rigorous phenomenological approach, and none have been
      conducted in Italy. AIM: To describe the lived experience of the caregivers of HF
      patients. METHODS: A hermeneutic phenomenological method was used. Caregivers
      were enrolled in a HF clinic in central Italy. Interviews were analysed using a
      phenomenological approach. Credibility, dependability, confirmability and
      transferability were adopted in order to strengthen trustworthiness. FINDINGS:
      Thirty HF caregivers (mean age: 53 years) were enrolled. Of these, 63% of the
      caregivers were female and 80% were patients' spouses or children. Six themes
      emerged: (1) fear and worry related to the illness; (2) life changes and
      restrictions; (3) burden due to caregiving; (4) uncertainty about illness
      management; (5) helping patients to cope with the illness; and (6) love and
      affection towards the patient. CONCLUSION: The findings of our study may help
      providers to guide interventions for HF caregivers. Providers should be
      supportive of caregivers and provide them with education in order to reduce their
      fears and worries about the illness and to handle the course of HF and its
      symptoms. An empathetic and practical approach with caregivers that considers the
      patient-caregiver relationship may help caregivers to cope with the changes and
      restrictions that caregiving brings to their lives and to reduce their burden.

PMID- 28447881
TI  - Clinical and duplex ultrasound evaluation of lower extremities varicose veins - a
      practical guideline.
AB  - Lower extremities varicose veins are among the most frequent diseases in the
      general population. They can cause complaints with a deterioration of the quality
      of life and are associated with potentially threatening clinical conditions such
      as chronic venous ulceration, haemorrhage from ruptured varicose veins, and
      venous thromboembolism. An accurate diagnostic work-up is crucial to confirm the
      presence and the extension of the venous problem, in order to obtain an optimal
      management of the condition. In the past years, great efforts have been made to
      reach an international consensus on the terminology, the symptomatology, the
      classification, and the duplex ultrasound examination of lower extremities
      varicose veins. Mainly guided by these consensus documents, the present article
      describes the diagnostic work-up of lower extremities varicose veins, based on a
      careful medical history, physical examination, and duplex ultrasound examination.

PMID- 28447880
TI  - Resistance Training in Youth: Laying the Foundation for Injury Prevention and
      Physical Literacy.
AB  - CONTEXT: The rising incidence of physical activity- and sports-related injuries
      has prompted the present-day investigation of resistance training as a potential
      means of injury prevention and physical literacy development among youth.
      EVIDENCE ACQUISITION: Relevant studies on the topics of athlete development,
      physical literacy, resistance training, and injury prevention in children and
      adolescents were reviewed (PubMed and Sports Discus, 1982-2016). Recommendations
      from consensus guidelines and position statements applicable to resistance
      training and injury prevention in youth, in addition to young athlete
      development, were reviewed. Additionally, hand searches, expert requests, article
      reference lists, and gray literature were utilized and reviewed for pertinent
      content. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS:
      Youth throughout the physical activity spectrum are at risk for physical activity
      and sports-related injury. Of highest priority are early specializers,
      physically inactive youth, and young girls, owing to increased injury rates.
      Resistance training among these at-risk populations has been shown to reduce
      injury risk by up to 68% and improve sports performance and health measures, in
      addition to accelerating the development of physical literacy. Recent
      recommendations, position statements, and national initiatives advocate for the
      incorporation of resistance training with qualified instruction among these
      groups. CONCLUSION: Resistance training in addition to free play and other
      structured physical activity training can serve as a protective means against
      injury and a positive catalyst for the development of physical literacy to offset
      the impact of diminishing physical activity and early sport specialization in
      today's youth.

PMID- 28447882
TI  - Development of novel amisulpride-loaded solid self-nanoemulsifying tablets:
      preparation and pharmacokinetic evaluation in rabbits.
AB  - OBJECTIVE: The current investigation is focused on the formulation and in vivo
      evaluation of optimized solid self-nanoemulsifying drug delivery systems (S
      SNEDDS) of amisulpride (AMS) for improving its oral dissolution and
      bioavailability. METHODS: Liquid SNEDDS (L-SNEDDS) composed of CapryolTM 90
      (oil), Cremophor(r) RH40 (surfactant), and Transcutol(r) HP (co-surfactant) were
      transformed to solid systems via physical adsorption onto magnesium
      aluminometasilicate (Neusilin US2). Micromeretic studies and solid-state
      characterization of formulated S-SNEDDS were carried out, followed by tableting,
      tablet evaluation, and pharmacokinetic studies in rabbits. RESULTS: Micromeretic
      properties and solid-state characterization proved satisfactory flow properties
      with AMS present in a completely amorphous state. Formulated self-nanoemulsifying
      tablets revealed significant improvement in AMS dissolution compared with either
      directly compressed or commercial AMS tablets. In vivo pharmacokinetic study in
      rabbits emphasized significant improvements in tmax, AUC(0-12), and AUC(0
      infinity) at p < .05 with 1.26-folds improvement in relative bioavailability from
      the optimized self-nanoemulsifying tablets compared with the commercial product.
      CONCLUSIONS: S-SNEDDS can be a very useful approach for providing patient
      acceptable dosage forms with improved oral dissolution and biovailability.

PMID- 28447883
TI  - C-H Infrared Absorption and Solubility of Ethylene, Propyne, 2-methyl-2-butene,
      and 2-methyl-1, 3-butadiene (Isoprene) in Liquid Argon Solutions.
AB  - The solubility of ethylene (H2C=CH2), propyne (CH3-C=C-H), 2-methyl-2-butene (CH3
      CH=C(CH3)2), and isoprene or 2-methyl-1, 3-butadiene (H2C=C(CH3)-CH=CH2) in
      liquid argon has been measured using mid-infrared and near-infrared (NIR)
      absorption. Spectra were recorded in the C-H infrared (IR) region. Spectra were
      obtained at increasing solution composition until the magnitude of the integrated
      absorption band reached a maximum value, indicating a saturated solution. The
      approximate experimental solubilities are: (600 +/- 100) ppm at 92 K for
      ethylene, (22 +/- 9) ppm at 100 K for propyne, (9 +/- 5) ppm at 100 K for 2
      methyl-2-butene, and (12 +/- 2) ppm at 86 K for isoprene. The experimental
      solubility values at the corresponding temperature were used with solubility
      parameters of two separate models: the perturbed-chain statistical associating
      fluid theory (PC-SAFT) and the regular solution theory. Solvent-solute
      interaction parameters k12 (PC-SAFT) and [Formula: see text] (RST) were obtained
      for each solute in the presence of argon as the solvent. Data from experimental
      measurements are important for more realistic simulations of solubility of solids
      in cryogenic liquids.

PMID- 28447884
TI  - Do microRNAs play a role in the activity of plant-based vaccines?
AB  - INTRODUCTION: An important trend in vaccinology is the development of oral
      vaccines based on genetically modified plants. Areas covered: Several studies
      have suggested that dietary microRNAs from plants and other organisms are
      bioavailable upon oral ingestion exerting biological events in the host such as
      the modulation of gene expression in several cell types. Since oral plant-based
      vaccines rely on whole cells as vaccine delivery vehicles, miRNAs could play a
      role in the immunogenic activity of this type of vaccine. In the present report,
      this hypothesis is discussed under the light of recent evidence on the
      immunomodulatory activity exerted by miRNAs using in vitro and in vivo
      evaluations. Expert commentary: The ways to generate new knowledge and exploit
      the potential of miRNAs in the development of oral vaccines are discussed.

PMID- 28447885
TI  - Recovery from Coma Post-Cardiac Arrest Is Dependent on the Orexin Pathway.
AB  - Cardiac arrest (CA) affects >550,000 people annually in the United States whereas
      80-90% of survivors suffer from a comatose state. Arousal from coma is critical
      for recovery, but mechanisms of arousal are undefined. Orexin-A, a hypothalamic
      excitatory neuropeptide, has been linked to arousal deficits in various brain
      injuries. We investigated the orexinergic system's role in recovery from CA
      related neurological impairments, including arousal deficits. Using an asphyxial
      CA and resuscitation model in rats, we examine neurological recovery post
      resuscitation in conjunction with changes in orexin-A levels in cerebrospinal
      fluid (CSF) and orexin-expressing neurons. We also conduct pharmacological
      inhibition of orexin post-resuscitation. We show that recovery from neurological
      deficits begins between 4 and 24 h post-resuscitation, with additional recovery
      by 72 h post-resuscitation. Orexin-A levels in the CSF are lowest during periods
      of poorest arousal post-resuscitation (4 h) and recover to control levels by 24
      h. Immunostaining revealed that the number of orexin-A immunoreactive neurons
      declined at 4 h post-resuscitation, but increased to near normal levels by 24 h.
      There were no significant changes in the number of neurons expressing melanin
      concentrating hormone, another neuropeptide localized in similar hypothalamus
      regions. Last, administration of the dual orexin receptor antagonist, suvorexant,
      during the initial 24 h post-resuscitation, led to sustained neurological
      deficits. The orexin pathway is critical during early phases of neurological
      recovery post-CA. Blocking this early action leads to persistent neurological
      deficits. This is of considerable clinical interest given that suvorexant
      recently received U.S. Food and Drug Administration approval for insomnia
      treatment.

PMID- 28447886
TI  - Drug-induced hyperlactatemia.
AB  - BACKGROUND: Hyperlactatemia is common in critically ill patients and has a
      variety of etiologies. Medication toxicity remains an uncommon cause that
      providers often fail to recognize. In this article, we review several medications
      that cause hyperlactatemia in either therapeutic or supratherapeutic dosing. When
      known, the incidence, mortality, pathophysiology, and treatment options are
      discussed. METHODS: We performed a literature search using PUBMED and Google
      Scholar for English language articles published after 1980 regarding medication
      induced hyperlactatemia and its management. Our search string resulted in 798
      articles of which 138 articles met inclusion criteria and were relevant to the
      topic of our review. CONCLUSIONS: Hyperlactatemia is a relatively rare but life
      threatening toxicity of various medication classes. Discontinuation of the drug
      is always advised, and some toxicities are subject to specific antidotal
      treatment. If there is no apparent medical cause for hyperlactatemia (sepsis,
      hypotension, hypoxia), clinicians should consider a toxicological etiology.

PMID- 28447887
TI  - Cyclopiazonic Acid Is a Pathogenicity Factor for Aspergillus flavus and a
      Promising Target for Screening Germplasm for Ear Rot Resistance.
AB  - Aspergillus flavus, an opportunistic pathogen, contaminates maize and other key
      crops with carcinogenic aflatoxins (AFs). Besides AFs, A. flavus makes many more
      secondary metabolites (SMs) whose toxicity in insects or vertebrates has been
      studied. However, the role of SMs in the invasion of plant hosts by A. flavus
      remains to be investigated. Cyclopiazonic acid (CPA), a neurotoxic SM made by A.
      flavus, is a nanomolar inhibitor of endoplasmic reticulum calcium ATPases (ECAs)
      and a potent inducer of cell death in plants. We hypothesized that CPA, by virtue
      of its cytotoxicity, may serve as a key pathogenicity factor that kills plant
      cells and supports the saprophytic life style of the fungus while compromising
      the host defense response. This proposal was tested by two complementary
      approaches. A comparison of CPA levels among A. flavus isolates indicated that
      CPA may be a determinant of niche adaptation, i.e., isolates that colonize maize
      make more CPA than those restricted only to the soil. Further, mutants in the CPA
      biosynthetic pathway are less virulent in causing ear rot than their wild-type
      parent in field inoculation assays. Additionally, genes encoding ECAs are
      expressed in developing maize seeds and are induced by A. flavus infection.
      Building on these results, we developed a seedling assay in which maize roots
      were exposed to CPA, and cell death was measured as Evans Blue uptake. Among >40
      maize inbreds screened for CPA tolerance, inbreds with proven susceptibility to
      ear rot were also highly CPA sensitive. The publicly available data on resistance
      to silk colonization or AF contamination for many of the lines was also broadly
      correlated with their CPA sensitivity. In summary, our studies show that i) CPA
      serves as a key pathogenicity factor that enables the saprophytic life style of
      A. flavus and ii) maize inbreds are diverse in their tolerance to CPA. Taking
      advantage of this natural variation, we are currently pursuing both genome-wide
      and candidate gene approaches to identify novel components of maize resistance to
      Aspergillus ear rot.

PMID- 28447888
TI  - Impact of particle size and surface modification on gold nanoparticle penetration
      into human placental microtissues.
AB  - AIM: Nanoparticle-based drug carriers hold great promise for the development of
      targeted therapies in pregnancy with reduced off-target effects. Here, we
      performed a mechanistic in vitro study on placental localization and penetration
      of gold nanoparticles (AuNPs) in dependence of particle size and surface
      modification. MATERIALS & METHODS: AuNP uptake and penetration in human placental
      coculture microtissues was assessed by inductively coupled plasma-mass
      spectrometry, transmission electron microscopy and laser ablation-inductively
      coupled plasma-mass spectrometry. RESULTS: Higher uptake and deeper penetration
      was observed for smaller (3-4 nm) or sodium carboxylate-modified AuNPs than for
      larger (13-14 nm) or PEGylate AuNPs, which barely passed the trophoblast barrier
      layer. CONCLUSION: It is possible to steer placental uptake and penetration of
      AuNPs by tailoring their properties, which is a prerequisite for the development
      of targeted therapies in pregnancy.

PMID- 28447890
TI  - Response to the letter regarding "Is it really safe to withhold folinic acid when
      less than 1000 mg/m2 methotrexate is ingested?"

PMID- 28447889
TI  - Bone Marrow as a Hematopoietic Stem Cell Source for Gene Therapy in Sickle Cell
      Disease: Evidence from Rhesus and SCD Patients.
AB  - Steady state bone marrow (BM) is the preferred hematopoietic stem cell (HSC)
      source for gene therapy in sickle cell disease (SCD) due to the recognized risk
      of vaso-occlusive crisis during granulocyte colony-stimulating factor
      mobilization. We previously established clinically relevant HSC gene transfer in
      the rhesus model following transplantation of mobilized peripheral blood (PB)
      CD34+ cells transduced with lentiviral vectors. In this study, we examined steady
      state bone marrow (BM) in the rhesus competitive repopulation model and
      demonstrate similar gene marking in vitro and in vivo, as compared with mobilized
      PB CD34+ cells. We then evaluated PB and steady state BM in subjects with SCD and
      observed a higher frequency of CD34+ cells when compared with controls, likely
      due to enhanced hematopoiesis. However, CD34+ cell counts were reduced in both
      the PB and BM in patients treated with hydroxyurea, and hydroxyurea treatment
      strongly inhibited iPS cell generation from SCD subjects. Our data support that
      steady state BM is a useful HSC source for SCD gene therapy with similar
      transduction. The lower CD34+ percentages observed with hydroxyurea treatment
      warrants withholding hydroxyurea temporarily prior to harvesting HSCs. Our
      results are important for the design of gene targeting strategies for SCD.

PMID- 28447891
TI  - The 40th Meeting of the Editorial Board.

PMID- 28447892
TI  - Intracellular localisation of proteins to specific cellular areas by nanocapsule
      mediated delivery.
AB  - Nanocapsules are promising carriers with great potential for intracellular
      protein transport. Although many studies have intended to improve cell uptake
      efficacy, there is an increasing interest in understanding of subcellular
      distribution of cargoes inside cells, which is essential for purposeful delivery
      of biomolecules into specific sites within cells. Herein, we interrogate the
      intracellular localisation of exogenous proteins, including fluorescein
      isothiocyanate (FITC)-labelled bovine serum albumin (BSA) and green fluorescent
      protein (GFP), mediated by specially designed nanocapsules. The results show that
      the designed nanocapsules can deliver the two types of fluorescent proteins into
      different cellular destinations (cytosol, nucleus or the whole cell), depending
      on the composition of nanocapsules. Meanwhile, several impact factors that
      influence the distribution of proteins in cells have also been investigated, and
      the results suggest that the localisation of capsule-mediated proteins in cells
      is strongly affected by the surface properties of nanocapsules, the types of
      stabilisers and proteins, and environmental temperatures. The rational control of
      intracellular localised delivery of exogenous proteins as we demonstrated in this
      study might open new avenues to obtain desired magnitude of drug effects for
      modulating cell activity.

PMID- 28447893
TI  - Ultra-small solid archaeolipid nanoparticles for active targeting to macrophages
      of the inflamed mucosa.
AB  - AIM: Develop nanoparticulate agents for oral targeted delivery of dexamethasone
      (Dex) to macrophages of inflamed mucosa. MATERIALS & METHODS: Solid archaeolipid
      nanoparticles (SAN-Dex) (compritol/Halorubrum tebenquichense polar
      archaeolipids/soybean phosphatidylcholine/Tween-80 4; 0.9; 0.3; 3% w/w) loaded
      with Dex were prepared. Their mucopenetration, stability under digestion and in
      vitro anti-inflammatory activity, were determined. RESULTS: Ultra-small SAN-Dex
      strongly reduced the levels of TNF-alpha, IL-6 and IL-12 on J774A1 cells
      stimulated with lipopolysaccharides as compared with free Dex or loaded in
      ordinary solid lipid nanoparticles-Dex. After in vitro digestion, the anti
      inflammatory activity of SAN-Dex was retained, while that of solid lipid
      nanoparticles-Dex was lost. CONCLUSION: Because of their structural and
      pharmacodynamic features, SAN-Dex may be suitable for oral targeted delivery to
      inflamed mucosa.

PMID- 28447894
TI  - Strategic Resource Use for Learning: A Self-Administered Intervention That Guides
      Self-Reflection on Effective Resource Use Enhances Academic Performance.
AB  - Many educational policies provide learners with more resources (e.g., new
      learning activities, study materials, or technologies), but less often do they
      address whether students are using these resources effectively. We hypothesized
      that making students more self-reflective about how they should approach their
      learning with the resources available to them would improve their class
      performance. We designed a novel Strategic Resource Use intervention that
      students could self-administer online and tested its effects in two cohorts of a
      college-level introductory statistics class. Before each exam, students randomly
      assigned to the treatment condition strategized about which academic resources
      they would use for studying, why each resource would be useful, and how they
      would use their resources. Students randomly assigned to the treatment condition
      reported being more self-reflective about their learning throughout the class,
      used their resources more effectively, and outperformed students in the control
      condition by an average of one third of a letter grade in the class.

PMID- 28447895
TI  - Compensatory Function of the Diaphragm after High Cervical Hemisection in the
      Rat.
AB  - Unilateral high cervical spinal hemisection (i.e., C2Hx) interrupts the
      respiratory bulbospinal pathway and results in paralysis of the hemidiaphragm.
      The ipsilateral diaphragmatic activity can partially recover over weeks to
      months; however, its contribution to the tidal volume generation is less than
      20%. Accordingly, we hypothesized that the contralateral diaphragm exerts a
      compensatory function to maintain the essential ventilation following C2Hx. The
      cardiorespiratory pattern and bilateral diaphragm electromyogram (EMG) signals
      were measured in urethane-anesthetized and spontaneously breathing adult rats at
      1 day, and 2 or 8 weeks post-C2Hx or C2 laminectomy. The functional contribution
      of the diaphragm was assessed by measuring immediate changes of the tidal volume
      following phrenic nerve section. At 1 day post-injury, the tidal volume was
      significantly reduced after contralateral phrenicotomy in C2Hx animals (54 +/- 3%
      decline) compared with uninjured controls (20 +/- 2% decline). Moreover, the
      arterial carbon dioxide partial pressure was significantly elevated in C2Hx
      animals (from 76 +/- 8 mmHg to 117 +/- 5 mmHg) but not in uninjured animals (from
      51 +/- 4 mmHg to 55 +/- 3 mmHg). By 2 and 8 weeks post-injury, contralateral
      phrenicotomy still caused a greater reduction in the tidal volume in C2Hx than in
      uninjured animals, and the percentage decline of the tidal volume was similar to
      the response at 1 day post-injury. These data suggested that unilateral cervical
      spinal cord injury induced a persistent compensatory plasticity in the
      contralateral diaphragm, which plays a critical role in maintenance of essential
      ventilation.

PMID- 28447896
TI  - Nanoemulsion is an effective antimicrobial for methicillin-resistant
      Staphylococcus aureus in infected wounds.
AB  - AIM: To develop NB-201, a nanoemulsion compound, as a novel microbicidal agent
      against methicillin-resistant Staphylococcus aureus (MRSA) infection, which is a
      common threat to public health but with limited therapeutic options. MATERIALS &
      METHODS: NB-201 was tested in in vitro and in vivo murine and porcine models
      infected with MRSA. RESULTS: Topical treatment of MRSA-infected wounds with NB
      201 significantly decreased bacterial load and had no toxic effects on healthy
      skin tissues. NB-201 attenuated neutrophil sequestration in MRSA-infected wounds
      and inhibited epidermal and deep dermal inflammation. The levels of
      proinflammatory cytokines were reduced in NB-201-treated MRSA-infected wounds.
      CONCLUSION: NB-201 can greatly reduce inflammation characteristic of infected
      wounds and has antimicrobial activity that effectively kills MRSA regardless of
      the genetic basis of antibiotic resistance.

PMID- 28447897
TI  - Specific hepatic stellate cell-penetrating peptide targeted delivery of a KLA
      peptide reduces collagen accumulation by inducing apoptosis.
AB  - Liver fibrosis is an aberrant wound-healing process to chronic hepatic
      inflammation and is characterized by excessive accumulation of extracellular
      matrix (ECM) that is produced by activated hepatic stellate cells (HSCs). Thus,
      activated HSCs play a key role in the pathogenesis of liver fibrosis and are a
      potential target for the treatment of liver fibrosis. Herein, we report that a
      specific HSC-penetrating peptide reduced collagen accumulation by inducing the
      apoptosis of HSC-T6 cells. We first screened HSC-specific transduction peptides
      and identified a novel HSC-targeted cell-penetrating peptide (HTP) that
      specifically interacted with HSC-T6 cells. A chimeric peptide termed HTPK25 was
      consequently generated by coupling HTP with the antimicrobial peptide KLA, which
      is capable of initiating cell apoptosis in mammalian cells. HTPK25 entered cells
      in a dose-dependent manner, reduced the cell viability and induced apoptosis via
      the caspase 3 pathway in HSC-T6 cells. Furthermore, HTPK25 inhibited the alpha
      smooth muscle actin and collagen I expression in HSC-T6 cells. Our results
      demonstrated that the HTP was able to specifically and efficiently deliver the
      KLA peptide into HSC-T6 cells to induce apoptosis, indicating that HTP-delivered
      functional agents may present a promising approach for liver fibrosis therapy.

PMID- 28447898
TI  - Splenic Epstein-Barr Virus-Associated Inflammatory Pseudotumor.
AB  - Splenic inflammatory pseudotumor (IPT) is an uncommon lesion with an inflammatory
      morphologic aspect that often poses a diagnostic challenge. The etiology of IPT
      can be infectious, autoimmune, reactive, or neoplastic. Splenic Epstein-Barr
      virus (EBV)-associated IPTs form a subset of splenic IPTs in which there is a
      spindle cell component infected by EBV. The best characterized and most frequent
      subgroup of splenic EBV-associated IPT is IPT-like follicular dendritic cell
      tumor. This review also focusses on EBV-associated splenic IPTs without
      follicular dendritic cell marker expression. These lesions are less well
      characterized, making the differential diagnosis with other splenic lesions even
      more difficult. Recently, increased numbers of immunoglobulin G4-positive plasma
      cells and the presence of numerous granulomas have been reported in EBV
      associated IPTs, and this can add to the difficulties in recognizing the
      neoplastic nature of these lesions. Herein, we also review the epidemiology,
      clinical features, histologic morphology, immunohistochemistry, electron
      microscopy, and pathogenesis of EBV-associated IPTs.

PMID- 28447899
TI  - The American College of Surgeons, Minimum Standards for Hospitals, and the
      Provision of High-Quality Laboratory Services.
AB  - CONTEXT: - The first major project of the American College of Surgeons (Chicago,
      Illinois), founded in 1913, was implementing Minimum Standards for Hospitals. The
      1918 standard (1) established medical staff organizations in hospitals; (2)
      restricted membership to licensed practitioners in good standing; (3) mandated
      that the medical staff work with hospital administration to develop and adopt
      regulations and policies governing their professional work; (4) required
      standardized, accessible medical records; and (5) required availability of
      diagnostic and therapeutic facilities. One hundred years ago, these were radical
      expectations. OBJECTIVES: - To describe the origin, "marketing," and voluntary
      adoption of the 1918 standards, and to describe how the evolution of those
      standards profoundly affected laboratory medicine after 1926. DESIGN: - Available
      primary and secondary historical sources were reviewed. RESULTS: - The college
      had no legal mandate, so it used a highly consultative approach, funded by its
      membership and the Carnegie Foundation (New York, New York), to establish the
      Minimum Standards, followed by a nonthreatening mechanism to determine which
      hospitals met them. Simultaneously, the college educated the public to fuel their
      expectations. Compliance by more than 100-bed hospitals in the United States and
      Canada, although entirely voluntary, rose from negligible when first implemented
      in 1918 to more than 90% in only a few years. From 1922 to 1926, the American
      Society for Clinical Pathology (Chicago, Illinois) worked creatively with the
      college to establish Minimum Standards for "adequate" laboratory services.
      CONCLUSIONS: - The birth and implementation of this program exemplifies how a
      consultative approach with full engagement of grassroots stakeholders facilitated
      a voluntary, rapid, sweeping North America-wide change-management process. This
      program eventually evolved into the Joint Commission (Oakbrook Terrace,
      Illinois).

PMID- 28447900
TI  - AlphaGo, Deep Learning, and the Future of the Human Microscopist.

PMID- 28447901
TI  - Straw Men, Deep Learning, and the Future of the Human Microscopist: Response to
      "Artificial Intelligence and the Pathologist: Future Frenemies?"

PMID- 28447903
TI  - Low-Grade Sinonasal Sarcoma With Neural and Myogenic Features: A Recently
      Discovered Entity With Unique Features and Diagnostic Challenge.
AB  - Low-grade sinonasal sarcoma with neural and myogenic features is an entity
      recently described in the literature. Little is known about its etiopathogenesis,
      natural history, or optimal treatment. In fact, it has relatively unique
      findings: it has a distinctive cytogenetic signature, and it expresses both
      smooth muscle actin and S100 protein. However, its diagnosis is challenging on
      biopsies showing negative staining for these 2 markers. The differential
      diagnoses include fibrosarcoma, malignant peripheral nerve sheath tumors, and
      other benign and malignant lesions. A complete resection, with or without
      radiotherapy, is required because this lesion appears to be locally aggressive.
      However, the clinical outcome seems to be good. Low-grade sinonasal sarcoma with
      neural and myogenic features merits classification as an independent tumor in the
      next World Health Organization classification of head and neck tumors. Reports of
      additional cases are required to support its unique classification.

PMID- 28447902
TI  - Reporting Results of Molecular Tests: A Retrospective Examination of BRAF
      Mutation Reporting.
AB  - CONTEXT: - With enormous growth in the field of molecular pathology, the
      reporting of results gleaned from this testing is essential to guide patient
      care. OBJECTIVE: - To examine molecular reports from laboratories participating
      in proficiency testing for required elements to convey molecular laboratory test
      results to clinicians and patients. DESIGN: - Molecular laboratories
      participating in the College of American Pathologists (CAP) proficiency testing
      program for BRAF mutation analysis were solicited to submit examples of final
      reports from 2 separate proficiency testing reporting cycles. Reports were
      reviewed for the presence or absence of relevant components. RESULTS: - A total
      of 107 evaluable reports were received (57 demonstrating a positive result for
      the BRAF V600E mutation and 50 negative). Methods for BRAF testing varied, with
      95% (102 of 107) of reports adequately describing their assay methods and 87% (93
      of 107) of reports adequately describing the target(s) of their assays.
      Information on the analytic sensitivity of the assay was present in 74% (79 of
      107) of reports and 83% (89 of 107) reported at least 1 assay limitation, though
      only 34% (36 of 107) reported on variants not detected by their assays. Analytic
      and clinical interpretive comments were included in 99% (106 of 107) and 90% (96
      of 107) of reports, respectively. Of participants that perform a laboratory
      developed test, 88% (88 of 100) included language addressing the development of
      the assay. CONCLUSIONS: - Laboratories participating in BRAF proficiency testing
      through the CAP are including most of the required reporting elements to
      unambiguously convey molecular results. Laboratories should continue to strive to
      report these results in a concise and comprehensive manner.

PMID- 28447904
TI  - Fine-Needle Aspiration Versus Frozen Section in the Evaluation of Malignant
      Thyroid Nodules in Patients With the Diagnosis of Suspicious for Malignancy or
      Malignancy by Fine-Needle Aspiration.
AB  - CONTEXT: - The Bethesda System for Reporting Thyroid Cytopathology recommends
      against the use of intraoperative frozen section (FS) during lobectomy of a
      thyroid nodule with a fine-needle aspiration (FNA) diagnosis of malignant.
      Bethesda recommendations for FS in the FNA category of suspicious for malignancy
      (SFM) is less well-defined. In some institutions in China, FS examination is
      performed during lobectomy even for FNA-proven malignant cases. OBJECTIVE: - -To
      compare the efficacy of FNA versus FS in the evaluation of malignant thyroid
      lesions. DESIGN: - A 3-year retrospective analysis from a single institution was
      performed on cases with an FNA diagnosis of SFM or malignant with subsequent FS
      examination during thyroidectomy. The results of FNA and FS findings were
      compared to the final thyroidectomy pathology. RESULTS: - -A total of 5832
      thyroidectomy procedures were performed: 1265 cases had FNA and FS results
      available. Fine-needle aspiration gave a diagnosis of SFM to 306 cases and a
      diagnosis of malignant to 821 cases. Of the SFM cases, 10.5% (32 of 306) had
      benign/indeterminate, 4.6% (14 of 306) suspicious, and 84.9% (260 of 306)
      malignant FS results. Final pathology showed 56.3% (18 of 32), 64.3% (9 of 14),
      and 100% (260 of 260) malignancy rates, respectively. For the malignant FNA
      group, 10.0% (82 of 821) had benign/indeterminate, 4.4% (36 of 821) suspicious,
      and 85.6% (703 of 821) malignant FS results. The final pathology showed 96.4% (79
      of 82), 97.2% (35 of 36), and 99.9% (702 of 703) malignancy rates, respectively.
      CONCLUSIONS: - Frozen section should not be performed for the malignant FNA
      category because FS evaluation may result in 10% falsely negative findings.
      Performing FS for SFM may be better justified; however, more than half of FS
      cases read as benign in this category had malignant final pathology. Therefore,
      caution should be taken for FS results even in the SFM group.

PMID- 28447905
TI  - Artificial Intelligence and the Pathologist: Future Frenemies?

PMID- 28447906
TI  - Quantifying nanoparticle cellular uptake: which method is best?

PMID- 28447907
TI  - Nanotherapy of cancer by photoelectrons emitted from the surface of nanoparticles
      exposed to nonionizing ultraviolet radiation.
AB  - AIM: We introduce a new method for selectively destroying cancer cell organelles
      by electrons emitted from the surface of intracellularly localized nanoparticles
      exposed to the nonionizing ultraviolet (UV) radiation. METHODS: We propose to
      target cancerous intracellular organelles by nanoparticles and expose them to UV
      radiation with energy density safe for healthy tissue. RESULTS: We simulate the
      number of photoelectrons produced by the nanoparticles made of various metals and
      radii, calculate their kinetic energy and compare it to the threshold energy for
      producing biological damage. CONCLUSION: Exposure of metal nanoparticles to UV
      radiation generates photoelectrons with kinetic energies up to 11 eV, which is
      high enough to produce single- to double-strand breaks in the DNA and damage the
      cancerous cell organelles.

PMID- 28447908
TI  - Perceived Family Climate and Self-Esteem in Adolescents With ADHD: A Study With a
      Control Group.
AB  - OBJECTIVE: In this study, our objective is to assess the perception of family
      environments by adolescents with ADHD based on perceived expressed emotion (EE)
      and the self-esteem of the adolescents. METHOD: Uludag University Medical Faculty
      Hospital completed this study with 41 adolescents with ADHD and 35 control group
      participants who were matched based on age and gender. RESULTS: The total scores
      of perceived EE, described as a lack of emotional support, irritability, and
      intrusiveness, were significantly higher in ADHD group than in the control group.
      The group with ADHD also showed significantly lower self-esteem. There was a
      negative correlation between self-esteem scores and total perceived EE scores in
      the ADHD group and the control group. CONCLUSION: This study showed that the
      adolescents with ADHD perceive less emotional support and higher levels of
      intrusiveness, with patients also describing their families as more irritating.
      Other results in this study show that adolescents with less emotional support
      possess lower self-esteem, as do adolescents with more irritable parents.

PMID- 28447909
TI  - Cholic acid-based novel micellar nanoplatform for delivering FDA-approved
      taxanes.
AB  - AIM: To structurally modify our existing cholic acid (CA)-based telodendrimer
      (TD; PEG5K-CA8) for effective micellar nanoencapsulation and delivery of the US
      FDA-approved members of taxane family. MATERIALS & METHODS: Generation of hybrid
      TDs was achieved by replacing four of the eight CAs with biocompatible organic
      moieties using solution-phase peptide synthesis. Drug loading was done using the
      standard evaporation method. RESULTS: Hybrid TDs can generate micelles with
      narrow size distributions, low critical micelle concentration values (1-6 MUM),
      better hematocompatibility and lack of in vitro cytotoxicity. CONCLUSION: Along
      with PEG5K-CA8, CA-based hybrid nanoplatform is the first of its kind that can
      stably encapsulate all three FDA-approved taxanes with nearly 100% efficiency up
      to 20% (w/w) loading.

PMID- 28447911
TI  - Is There a Role for Ovarian Cancer Screening in High-Risk Women?

PMID- 28447910
TI  - Chemical and biological assessment of metal organic frameworks (MOFs) in
      pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial
      hypertension therapy.
AB  - Pulmonary arterial hypertension (PAH) is a progressive and debilitating
      condition. Despite promoting vasodilation, current drugs have a therapeutic
      window within which they are limited by systemic side effects. Nanomedicine uses
      nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize
      that this approach could be used to deliver PAH drugs avoiding the systemic
      circulation. Here we report the use of iron metal organic framework (MOF) MIL-89
      and PEGylated MIL-89 (MIL-89 PEG) as suitable carriers for PAH drugs. We assessed
      their effects on viability and inflammatory responses in a wide range of lung
      cells including endothelial cells grown from blood of donors with/without PAH.
      Both MOFs conformed to the predicted structures with MIL-89 PEG being more stable
      at room temperature. At concentrations up to 10 or 30 ug/mL, toxicity was only
      seen in pulmonary artery smooth muscle cells where both MOFs reduced cell
      viability and CXCL8 release. In endothelial cells from both control donors and
      PAH patients, both preparations inhibited the release of CXCL8 and endothelin-1
      and in macrophages inhibited inducible nitric oxide synthase activity. Finally,
      MIL-89 was well-tolerated and accumulated in the rat lungs when given in vivo.
      Thus, the prototypes MIL-89 and MIL-89 PEG with core capacity suitable to
      accommodate PAH drugs are relatively non-toxic and may have the added advantage
      of being anti-inflammatory and reducing the release of endothelin-1. These data
      are consistent with the idea that these materials may not only be useful as drug
      carriers in PAH but also offer some therapeutic benefit in their own right.

PMID- 28447913
TI  - Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate
      Cancer.
AB  - Purpose The association between exposure to testosterone replacement therapy
      (TRT) and prostate cancer risk is controversial. The objective was to examine
      this association through nationwide, population-based registry data. Methods We
      performed a nested case-control study in the National Prostate Cancer Register of
      Sweden, which includes all 38,570 prostate cancer cases diagnosed from 2009 to
      2012, and 192,838 age-matched men free of prostate cancer. Multivariable
      conditional logistic regression was used to examine associations between TRT and
      risk of prostate cancer (overall, favorable, and aggressive). Results Two hundred
      eighty-four patients with prostate cancer (1%) and 1,378 control cases (1%)
      filled prescriptions for TRT. In multivariable analysis, no association was found
      between TRT and overall prostate cancer risk (odds ratio [OR], 1.03; 95% CI, 0.90
      to 1.17). However, patients who received TRT had more favorable-risk prostate
      cancer (OR, 1.35; 95% CI, 1.16 to 1.56) and a lower risk of aggressive prostate
      cancer (OR, 0.50; 95% CI, 0.37 to 0.67). The increase in favorable-risk prostate
      cancer was already observed within the first year of TRT (OR, 1.61; 95% CI, 1.10
      to 2.34), whereas the lower risk of aggressive disease was observed after > 1
      year of TRT (OR, 0.44; 95% CI, 0.32 to 0.61). After adjusting for previous biopsy
      findings as an indicator of diagnostic activity, TRT remained significantly
      associated with more favorable-risk prostate cancer and lower risk of aggressive
      prostate cancer. Conclusion The early increase in favorable-risk prostate cancer
      among patients who received TRT suggests a detection bias, whereas the decrease
      in risk of aggressive prostate cancer is a novel finding that warrants further
      investigation.

PMID- 28447914
TI  - Diagnosis of Life-Threatening Alpha-Gal Food Allergy Appears to Be Patient
      Driven.
AB  - OBJECTIVE: Patients exhibiting life-threatening symptoms associated with the
      alpha-gal food allergy (delayed urticaria or anaphylaxis due to mammalian meat)
      are frequently undiagnosed, causing unnecessary emergency department (ED) and
      health care visits, and extensive pain and suffering. This study aimed to
      determine the path to diagnosis experienced by alpha-gal patients. METHODS:
      Semistructured interviews were conducted from March to June 2016 with a
      chronological systematic sample of approximately 10% of patients diagnosed with
      alpha-gal and treated by the University of North Carolina Allergy and Immunology
      Clinic (n = 28). Main outcome measures included average length of time between
      first symptoms' appearance and diagnosis, number and type of health care
      encounters en route to diagnosis, and typical symptom severity. RESULTS: Six
      interviewees (21%) were diagnosed within a year of experiencing symptoms, of the
      remaining 22, mean time to diagnosis was 7.1 years. In over 100 medical
      encounters (including 28 ED visits and 2 urgent care) the correct diagnosis or
      effective diagnosing referral occurred less than 10% of the time. Seventy-one
      percent (20/28) described their first symptoms as severe. More patients found the
      allergist specializing in this condition on their own (n = 12; 43%) than those
      who were formally diagnosed or received referrals (n = 10; 36%) through the
      health care system. CONCLUSIONS: The medical community is challenged to stay
      abreast of emerging and newly uncovered illnesses through traditional medical
      literature communication channels. Presently, patients more often discover a
      diagnosis of alpha-gal allergy by using information resources on their own than
      by presenting to the ED with anaphylaxis.

PMID- 28447912
TI  - Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the
      Global, Multicenter RET Registry.
AB  - Purpose In addition to prospective trials for non-small-cell lung cancers
      (NSCLCs) that are driven by less common genomic alterations, registries provide
      complementary information on patient response to targeted therapies. Here, we
      present the results of an international registry of patients with RET-rearranged
      NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET
      directed therapy thus far. Methods A global, multicenter network of thoracic
      oncologists identified patients with pathologically confirmed NSCLC that harbored
      a RET rearrangement. Molecular profiling was performed locally by reverse
      transcriptase polymerase chain reaction, fluorescence in situ hybridization, or
      next-generation sequencing. Anonymized data-clinical, pathologic, and molecular
      features-were collected centrally and analyzed by an independent statistician.
      Best response to RET tyrosine kinase inhibition administered outside of a
      clinical trial was determined by RECIST v1.1. Results By April 2016, 165 patients
      with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United
      States were accrued. Median age was 61 years (range, 29 to 89 years). The
      majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and
      advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of
      those patients, 53 received one or more RET tyrosine kinase inhibitors in
      sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10
      patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two
      patients), nintedanib (two patients), ponatinib (two patients), and regorafenib
      (one patient). The rate of any complete or partial response to cabozantinib,
      vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses
      were observed with lenvantinib and nintedanib. Median progression-free survival
      was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8
      months (95% CI, 3.9 to 14.3 months). Conclusion Available multikinase inhibitors
      had limited activity in patients with RET-rearranged NSCLC in this retrospective
      study. Further investigation of the biology of RET-rearranged lung cancers and
      identification of new targeted therapeutics will be required to improve outcomes
      for these patients.

PMID- 28447915
TI  - Enhancing the Career Planning Self-Determination of Young Adults with Mental
      Health Challenges.
AB  - The impact of an intervention on the self-determination and career planning
      engagement of young adults with mental health challenges was studied. Sixty-seven
      young adults, 20 to 30 years of age, with mental health diagnoses (e.g.,
      depression, bipolar disorder) were randomly assigned to intervention and control
      groups. Statistically significant greater increases were made by the intervention
      group versus the control group for self-determination and career planning
      engagement, and self-determination at least partially mediated increases in
      career planning engagement. With career planning self-determination
      interventions, young adults with mental health challenges might be able to
      achieve better career and life outcomes than is typical for this population.

PMID- 28447916
TI  - Mothers with Physical Disabilities Caring for Young Children.
AB  - Seventy-one U.S. mothers with a physical disability who had a child aged 0 to 3
      years responded to a survey about the system of care used for their child.
      Results indicated that mothers participated in all different types of care
      (physical, comforting, playing, limit setting, and taking the child outside the
      home). Partners and participants' mothers provided the most assistance with care.
      Mothers were generally satisfied with assistance received from others. This
      article explores how mothers remain central to their children with others
      assisting with the child's care and the impact of such assistance on mothers'
      relationships with partners and children.

PMID- 28447917
TI  - Differences in Experiences of Discrimination in Accessing Social Services Among
      Transgender/Gender Nonconforming Individuals by (Dis)Ability.
AB  - Transgender and gender nonconforming (GNC) individuals frequently experience
      discrimination and potentially a lack of respect from service providers,
      suggesting they have decreased access to professionals with cultural competency.
      Similarly, people with disabilities experience higher levels of discrimination in
      social services than their nondisabled counterparts. From an intersectional
      perspective, this study examines rates of discrimination in accessing social
      services faced by transgender and GNC people, comparing across ability. Data
      indicate that although transgender and GNC individuals of all abilities
      experience gender-based discrimination when accessing social services, those with
      disabilities experience higher levels of antitransgender discrimination in mental
      health centers, rape crisis centers, and domestic violence shelters.

PMID- 28447918
TI  - No relation between biomarkers at age 47-49 and aortic diameter after 14-19 years
      of follow-up - a population-based study.
AB  - BACKGROUND: Biomarkers reflecting diverse pathophysiological pathways may play an
      important role in the pathogenesis of abdominal aortic aneurysm (aortic diameter
      >=30 mm, AAA), levels of many biomarkers are elevated and correlated to aortic
      diameter among 65-year-old men undergoing ultrasound (US) screening for AAA.
      PROBANDS AND METHODS: To evaluate potential relationships between biomarkers and
      aortic dilatation after long-term follow-up, levels of C-reactive protein (CRP),
      proneurotensin (PNT), copeptin (CPT), lipoprotein-associated phospholipase 2 (Lp
      PLA2), cystatin C (Cyst C), midregional proatrial natriuretic peptide (MR
      proANP), and midregional proadrenomedullin (MR-proADM) were measured in 117
      subjects (114 [97 %] men) aged 47-49 in a prospective population-based cohort
      study, and related to aortic diameter at US examination of the aorta after 14-19
      years of follow-up. RESULTS: Biomarker levels at baseline did not correlate with
      aortic diameter after 14-19 years of follow up (CRP [r = 0.153], PNT [r = 0.070],
      CPT [r = -.156], Lp-PLA2 [r = .024], Cyst C [r = -.015], MR-proANP [r = 0.014],
      MR-proADM [r = -.117]). Adjusting for age and smoking at baseline in a linear
      regression model did not reveal any significant correlations. CONCLUSIONS: Tested
      biomarker levels at age 47-49 were not associated with aortic diameter at
      ultrasound examination after 14-19 years of follow-up. If there are relationships
      between these biomarkers and aortic dilatation, they are not relevant until
      closer to AAA diagnosis.

PMID- 28447919
TI  - Postpartum dyspareunia and sexual functioning: a prospective cohort study.
AB  - OBJECTIVES: Sexual functioning is an important concern for women in the
      postpartum period. The aim of this research was to investigate the prevalence and
      determinants of dyspareunia and sexual dysfunction before and after childbirth.
      METHODS: Between November 2013 and April 2014, 109 women in their third trimester
      of pregnancy were enrolled in a prospective cohort study at Ghent University
      Hospital. Dyspareunia, sexual functioning and quality of life (QOL) were
      evaluated at enrolment and again 6 weeks and 6 months postpartum. Sexual
      functioning and QOL were assessed using validated self-report questionnaires: the
      Female Sexual Function Index and the Short Form-36 health survey. Dyspareunia was
      evaluated by a specific self-developed questionnaire. RESULTS: One hundred and
      nine women were enrolled; respectively, 71 (65.1%), 66 (60.6%) and 64 (58.7%)
      women returned the questionnaires prepartum, and 6 weeks and 6 months postpartum.
      Sexual functioning at 6 weeks was predictive of sexual functioning at 6 months
      postpartum (rs = 0.345, p = .015). The prevalence of dyspareunia in the third
      trimester of pregnancy, and 6 weeks and 6 months postpartum was, respectively,
      32.8%, 51.0% and 40.7%. The severity of pain decreased significantly between 6
      weeks and 6 months postpartum (p = .003). In the first 6 weeks postpartum, the
      degree of dyspareunia was significantly associated with breastfeeding (p = .045)
      and primiparity (p = .020). At 6 months, only the association with primiparity
      remained significant (p = .022). CONCLUSIONS: The impaired postpartum sexual
      functioning, the high prevalence of dyspareunia postpartum and their impact on
      QOL indicate the need for further investigation and extensive counselling of
      pregnant women, especially primiparous women, about sexuality after childbirth.

PMID- 28447920
TI  - Prolonged circulation and increased tumor accumulation of liposomal vincristine
      in a mouse model of rhabdomyosarcoma.
AB  - AIM: Our goal was to improve vincristine (VCR) based rhabdomyosarcoma (RMS)
      therapy by encapsulating the drug into liposomes. A targeting strategy was
      attempted to enhance tumor accumulation. MATERIALS & METHODS: VCR was loaded in
      control and peptide-decorated liposomes via an active method. The interaction of
      an RMS-specific peptide with the presumed target furin and the cellular uptake of
      both liposomal groups were studied in vitro. Pharmacokinetics and biodistribution
      of VCR-containing liposomes were assessed in an RMS xenograft mouse model.
      RESULTS: Liposomes ensured high VCR concentration in plasma and in the tumor.
      Peptide-decorated liposomes showed modest uptake in RMS cells. CONCLUSION: The
      investigated peptide-modified liposomal formulation may not be optimal for furin
      mediated RMS targeting. Nevertheless, VCR-loaded liposomes could serve as a
      delivery platform for experimental RMS.

PMID- 28447921
TI  - The effectiveness of acute normolvolemic hemodilution and autologous prime on
      intraoperative blood management during cardiac surgery.
AB  - OBJECTIVE: Intraoperative blood management during cardiac surgery is a
      multifaceted process incorporating various interventions directed at optimizing
      oxygen delivery and enhancing hemostasis. The purpose of this study was to
      evaluate the effects of acute normovolemic hemodilution (ANH) and autologous
      priming (AP) on preserving the hematocrit during cardiopulmonary bypass (CPB).
      METHOD: Case records from a national registry of adult patients who underwent
      cardiac surgery between January and October 2016 were reviewed. Groups were
      determined as follows: ANH, AP, ANH+AP or Neither. Primary endpoint was first the
      hematocrit on CPB with secondary endpoints of hematocrit drift and red blood cell
      (RBC) transfusion rate. RESULTS: Eighteen thousand and twenty-four (18,024)
      consecutive patients were reviewed. The first CPB hematocrit was lowest in the
      ANH group (26.5%+/-4.4%) and highest in ANH+AP patients (27.5%+/-4.8%) (p<0.001).
      The change in hematocrit was greatest in the ANH group (8.3%+/-3.9%) compared to
      both the AP (6.4%+/-3.8%) and ANH+AP (6.9%+/-4.1%) groups (p<0.001).
      Intraoperative RBC transfusions were as follows: ANH 26 (7.8%), AP 2,531 (20.0%),
      ANH+AP 287 (10.3%) and Neither 592 (26.7%) (p<0.001). CONCLUSIONS: Regression
      results show that the use of ANH will result in the greatest decline in
      hematocrit values. When combined with AP, higher hematocrits and lower
      transfusions were seen.

PMID- 28447922
TI  - Are You Being Served? The Relationship between School Climate for Service and
      Teachers' Engagement, Satisfaction, and Intention to Leave: A Moderated Mediation
      Model.
AB  - The notion of service has been receiving increasing attention in organizational
      psychology literature in recent years, due to the client-oriented managerial
      movement. Yet, little to no attention has been paid to the service notion in
      educational psychology despite its high relevance to educational settings, given
      the pressure to be more service-oriented and possess a client-focused state of
      mind. The present study explores the notion of service in school domains by
      examining the joint effects of climate for service and the internal service in
      schools on teachers' work attitudes: work engagement, job satisfaction, and
      intention to leave their work. The notion of climate for service emphasizes the
      school's attitude of teachers as service providers to its clients (students and
      their parents); internal climate emphasizes the school's attitude of providing
      service to its teaching staff. The study was conducted via a sample of 423
      teachers from 30 different schools in Israel. We hypothesized that the indirect
      relationship between the climate for service and teachers' job satisfaction and
      intention to leave work would be mediated by teacher work engagement. Our
      findings supported this hypothesis. Moreover, this indirect relationship via
      teacher work engagement was demonstrated most strongly when the internal service
      quality received was high, providing teachers with the capability to deliver what
      the service climate motivates them to do. Therefore, service-oriented resources
      both climate for service and internal service-may be crucial in affecting
      teachers work attitudes and should be specifically targeted by principals and
      other educational decision makers.

PMID- 28447924
TI  - The Effects of Messages about the Causes of Obesity on Disciplinary Action
      Decisions for Overweight Employees.
AB  - We investigated the impact of messages about the causes of obesity (controllable
      or uncontrollable) on the disciplinary action consequences selected for obese
      employees in response to a work-related mistake. Participants read about either
      the controllable or uncontrollable causes of obesity before reviewing an
      ostensible employee file that included a description of an employee mistake.
      Depending on condition, the file contained a photo of the employee that either
      depicted them as obese or average weight. Participants were more willing to
      withhold a raise or promotion from an obese employee than from an average-weight
      employee. Further, there was little evidence that the messages about the causes
      of obesity affected participants' perceived control and self-efficacy for healthy
      behaviors.

PMID- 28447925
TI  - Luminex Solid-Phase Crossmatch for De Novo Donor-Specific Antibodies in Living
      Donor Related Transplants.
AB  - OBJECTIVES: There are no reports of de novo donor-specific antibody monitoring by
      a low-cost solid-phase crossmatch assay using donor lysate after renal
      transplant. MATERIALS AND METHODS: We prospectively evaluated 121 complement
      dependant cytotoxicity crossmatch-negative living-donor kidney transplant
      recipients for development of de novo donor-specific antibodies (class I and II
      HLA) by solid-phase crossmatch Luminex assay after transplant. RESULTS: Of 121
      recipients in our study group, 26 (21.5%) developed de novo donor-specific
      antibody within 3 months after transplant. Fifteen (58%) of these 26 recipients
      developed class II de novo donor-specific antibody, 8 patients (30%) developed
      class I, and 3 (12%) developed both class I and class II. Of the remaining 95
      patients (79%) who did not develop de novo donor-specific antibody, 6 (33.3%) had
      antibody-mediated rejection with glomerulitis (2 with C4d-positive disease).
      Donor-specific antibody was detected by Luminex solid-phase crossmatch in 18
      patients (5 with class I, 11 with class II, and 2 with both class I and II), all
      with no evidence of clinical rejection. Development of de novo donor-specific
      antibody detected by solid-phase crossmatch was associated with more acute
      rejection (31% in de novo donor-specific antibody-positive group versus 19% in
      the negative group). The positive group had more antibody-mediated rejection (75%
      of acute rejections), whereas only 33.3% of acute rejections in the negative
      group were antibody-mediated rejection. Of 12 patients with antibody-mediated
      rejection, 9 were C4d negative (75%) and were diagnosed by donor-specific
      antibody positivity detected by solid-phase cros?match testing and histologic
      findings. The use of donor lysate in solid-phase crossmatch assays is more
      economical than the single-antigen bead Luminex assay (per test cost of US $45.20
      vs $403.20).

PMID- 28447926
TI  - Treatment of Primary Central Nervous System Posttransplant Lymphoproliferative
      Disorder in an Adult Kidney Transplant Recipient: A Case Report.
AB  - Posttransplant lymphoproliferative disorder is a serious complication of solid
      organ transplant. Extranodal involvement is common; however, isolated involvement
      of the central nervous system is extremely rare and represents a particularly
      difficult therapeutic challenge with no current consensus on optimal treatment.
      Here, we describe a 70-year-old woman who developed Epstein-Barr virus-related
      primary central nervous system lymphoma 19 months after kidney transplant.
      Immunosuppression was reduced, and the patient was started on high-dose
      methotrexate, which was complicated by acute kidney injury and discontinued. She
      then received a rituximab and temozolomide chemotherapeutic regimen and achieved
      complete clinical response. Seventeen months after diagnosis, she is alive and
      has not developed any other posttransplant lymphoproliferative disorder. We
      review the current literature and discuss treatment options for patients with
      primary central nervous system posttransplant lymphoproliferative disorder
      following kidney transplant.

PMID- 28447927
TI  - Unexpected Positive Prospective Crossmatches in Organ Transplant.
AB  - Preformed donor-specific antibodies against human leukocyte antigen can induce
      antibody-mediated rejection after organ transplant. Hence, future transplant
      recipients undergo pretransplant screening for preformed antibodies (ie, virtual
      crossmatch). Subsequently, prospective (analytic) crossmatching is performed
      using conventional, complement-dependent cytotoxicity assays and/or flow
      cytometry-based methods. The present article reviews factors that must be
      considered when unexpected, positive, prospective crossmatches are observed.
      First, the prozone effect caused by the interference of complement or
      immunoglobulin M must be abrogated by treating the serum with moderate heat,
      dilution, hypotonic dialysis, EDTA, or dithiothreitol. Second, the physician must
      check for the presence of potentially interfering autoantibodies (in a context of
      autoimmune disease or human immunodeficiency virus infection) or therapeutic
      antibodies (such as rituximab and antithymocyte globulin). In conclusion,
      knowledge of each assay's technical characteristics will enable the physician to
      reliably interpret any discrepancies. The reasons for an unexpected, positive,
      prospective crossmatch must be elucidated before transplant to ensure efficient
      organ allocation and optimize patient outcomes.

PMID- 28447928
TI  - Evaluation of Three-Dimensional Versus Conventional Laparoscopy for Kidney
      Transplant Procedures in a Human Cadaveric Model.
AB  - OBJECTIVES: There are increased reports that kidney transplant can be performed
      by laparoscopic surgery. The further development of this technique could
      revolutionize human kidney transplant surgery. However, laparoscopic kidney
      transplant demands a high level of skill for vascular anastomoses. The emerging
      technology of the three-dimensional, high-definition laparoscopic system may
      facilitate the application of this technique. Therefore, in this study, we
      evaluated this system in performing kidney transplant surgery versus the two
      dimensional laparoscopic system. MATERIALS AND METHODS: Four fresh-frozen human
      cadavers were used in this study, with 2 for the 3-dimensional and 2 for the 2
      dimensional system. Kidneys were retrieved by using the retroperitoneoscopic
      technique for living donor nephrectomy from the same cadaver. The kidney graft
      was transplanted at the right iliac fossa using a laparoscopic technique by
      extraperitoneal approach. The procedure was recorded, and the vessel anastomotic
      time was analyzed. RESULTS: Kidney transplant procedures were conducted
      successfully in the 3-dimensional, high-definition and the 2-dimensional groups.
      We recorded no significant differences in terms of vessel anastomotic time
      between the 2 groups. The total surgery time was shorter in the 3-dimensional,
      high-definition group than in the 2-dimensional group (P = .02). CONCLUSIONS:
      This pilot study reinforces that kidney transplant with either the 3-dimensional,
      high-definition or 2-dimensional laparoscopy is feasible in a human cadaveric
      model. The operation was the same as open kidney transplant, but the procedure
      was performed by a laparoscopic approach with a smaller incision.

PMID- 28447929
TI  - Five-Year Follow-Up on Transplanted Organs From Donors After Brain Death After
      Acute Stroke.
AB  - OBJECTIVES: Efficient intensive care donor management can help alleviate the
      shortage of organs for transplant. The aim of this study was to investigate the
      efficiency of management of donors after brain death from our neurointensive care
      unit. MATERIALS AND METHODS: We conducted a prospective observational 5-year
      follow-up on 29 transplanted organs from 14 brain-dead donors after acute stroke
      (7 subarachnoid and 4 intracerebral hemorrhages, 3 ischemic strokes). Mean age of
      donors was 56.2 +/- 8.70 years, and mean number of days of artificial ventilation
      was 5.0 +/- 3.84. We transplanted 27 kidneys and 2 livers to 29 patients with
      mean age of 55.3 +/- 9.76 years. No hearts or lungs were transplanted from these
      donors. RESULTS: Of the 27 patients who underwent kidney transplant, 21 patients
      (78%) lived 5 years; of those, 17 patients (63%) had functional grafts. One
      patient (4%) had a primary afunctional graft, and 3 patients (11%) had graft
      rejection (at 3, 15, and 41 mo). Six patients (22%) died after kidney transplant,
      with 1 patient in this group having a functional graft, 1 patient having a
      primary afunctional graft, and 4 patients (15%) having graft rejection (at 1, 12,
      44, and 56 mo). The 2 patients with liver transplants lived 5 years with
      functional grafts. CONCLUSIONS: The 5-year follow-up showed that organs from 14
      brain-dead donors improved and saved 19 lives, with 17 patients receiving kidney
      transplants and 2 patients receiving liver transplants. Another 7 patients had
      only partially improved quality of life.

PMID- 28447930
TI  - A Novel and Simple Method for Tracheal Intubation in a Swine Model: Preparing for
      the Era of Xenotransplantation.
AB  - OBJECTIVES: Organ transplant in humans is an established therapy for a variety of
      end-stage organ diseases. However, due to organ shortages and lack of donors, the
      need for xenotransplant has gradually increased. Xenotransplantation has great
      potential to solve many of the problems facing organ transplantation. Pigs are
      being developed as xenogeneic organ donors for use in humans. In this study, we
      propose a novel and simple method for tracheal intubation in a swine model using
      neuromuscular blocking agents and laryngeal mask airway. MATERIALS AND METHODS:
      Eight Yorkshire pigs were used for the 2 separate experiments, which were
      conducted 1 week apart. In the first experiment, an anesthesiologist with no
      previous comparable experience performed endotracheal intubation of pigs. One
      week later, using the same pig, a second experiment was performed by an
      experienced anesthesiologist. Anesthesia was induced with intramuscular injection
      of a mixture of 1 mg/kg xylazine (Rompun, Bayer Korea Ltd., Seoul, Korea) and 7
      mg/kg Zoletil (a mixture of tiletamine hydrochloride and zolazepam hydro
      chloride, Virbac Laboratory, Carros, France). The laryngeal mask was then placed,
      and 0.15 mg/kg vecuronium bromide was injected intravenously. Tracheal intubation
      was attempted after mask removal. The duration and number of intubation attempts
      were recorded, and the degree of intubation difficulty was scored. RESULTS: In
      all cases, the laryngeal mask was easily inserted, and endotracheal intubation
      was successfully completed. Oxygen saturation did not fall below 95%, and there
      were no hypoxemia episodes. Degree of intubation difficulty and duration were not
      significantly different between the 2 anesthesiologists. CONCLUSIONS: Tracheal
      intubation in our swine model was successfully performed using neuromuscular
      blocking agents and laryngeal masks without resulting in hypoxemia, with even
      anesthesiologists who are unfamiliar with endotracheal intubation of pigs easily
      able to do so using our protocol. Therefore, our protocol will enable all
      investigators to perform successful tracheal intubation in swine models.

PMID- 28447932
TI  - In Reply.

PMID- 28447933
TI  - Acute Decompensated Heart Failure: New Strategies for Improving Outcomes.
AB  - Acute decompensated heart failure is a common emergency department presentation
      with significant associated morbidity and mortality. Heart failure accounts for
      more than 1 million hospitalizations annually, with a steadily increasing
      incidence as our population ages. This issue reviews recent literature regarding
      appropriate management of emergency department presentations of acute
      decompensated heart failure, with special attention to newer medication options.
      Emergency department management and appropriate interventions are discussed,
      along with critical decision-making points in resuscitation for both hypertensive
      and hypotensive patients.

PMID- 28447934
TI  - Acute Kidney Injury in Pediatric Patients: Diagnosis and Management in the
      Emergency Department.
AB  - Pediatric acute kidney injury is a condition that is underdiagnosed among
      children seen in the emergency department, and it has been associated with
      significant morbidity and mortality, including increased risk for chronic kidney
      disease. The most common etiologies in pediatric patients are now known to be due
      to hypovolemia, sepsis, shock, and cardiac dysfunction. This issue compares 3
      classification systems for the diagnosis and staging of acute kidney injury and
      reviews the etiologies that lead to kidney injury in children. The management of
      pediatric acute kidney injury focuses on identifying patients at high risk,
      monitoring intravascular volume status, avoiding nephrotoxic medication exposure,
      and involving a pediatric nephrologist once acute kidney injury is diagnosed.

PMID- 28447936
TI  - PPP1R15A-mediated dephosphorylation of eIF2alpha is unaffected by Sephin1 or
      Guanabenz.
AB  - Dephosphorylation of translation initiation factor 2 (eIF2alpha) terminates
      signalling in the mammalian integrated stress response (ISR) and has emerged as a
      promising target for modifying the course of protein misfolding diseases. The [(o
      chlorobenzylidene)amino]guanidines (Guanabenz and Sephin1) have been proposed to
      exert protective effects against misfolding by interfering with eIF2alpha-P
      dephosphorylation through selective disruption of a PP1-PPP1R15A holophosphatase
      complex. Surprisingly, they proved inert in vitro affecting neither stability of
      the PP1-PPP1R15A complex nor substrate-specific dephosphorylation. Furthermore,
      eIF2alpha-P dephosphorylation, assessed by a kinase shut-off experiment,
      progressed normally in Sephin1-treated cells. Consistent with its role in
      defending proteostasis, Sephin1 attenuated the IRE1 branch of the endoplasmic
      reticulum unfolded protein response. However, repression was noted in both
      wildtype and Ppp1r15a deleted cells and in cells rendered ISR-deficient by CRISPR
      editing of the Eif2s1 locus to encode a non-phosphorylatable eIF2alpha
      (eIF2alphaS51A). These findings challenge the view that [(o
      chlorobenzylidene)amino]guanidines restore proteostasis by interfering with
      eIF2alpha-P dephosphorylation.

PMID- 28447935
TI  - Host-selected mutations converging on a global regulator drive an adaptive leap
      towards symbiosis in bacteria.
AB  - Host immune and physical barriers protect against pathogens but also impede the
      establishment of essential symbiotic partnerships. To reveal mechanisms by which
      beneficial organisms adapt to circumvent host defenses, we experimentally evolved
      ecologically distinct bioluminescent Vibrio fischeri by colonization and growth
      within the light organs of the squid Euprymna scolopes. Serial squid passaging of
      bacteria produced eight distinct mutations in the binK sensor kinase gene, which
      conferred an exceptional selective advantage that could be demonstrated through
      both empirical and theoretical analysis. Squid-adaptive binK alleles promoted
      colonization and immune evasion that were mediated by cell-associated matrices
      including symbiotic polysaccharide (Syp) and cellulose. binK variation also
      altered quorum sensing, raising the threshold for luminescence induction.
      Preexisting coordinated regulation of symbiosis traits by BinK presented an
      efficient solution where altered BinK function was the key to unlock multiple
      colonization barriers. These results identify a genetic basis for microbial
      adaptability and underscore the importance of hosts as selective agents that
      shape emergent symbiont populations.

PMID- 28447937
TI  - IL17 factors are early regulators in the gut epithelium during inflammatory
      response to Vibrio in the sea urchin larva.
AB  - IL17 cytokines are central mediators of mammalian immunity. In vertebrates, these
      factors derive from diverse cellular sources. Sea urchins share a molecular
      heritage with chordates that includes the IL17 system. Here, we characterize the
      role of epithelial expression of IL17 in the larval gut-associated immune
      response. The purple sea urchin genome encodes 10 IL17 subfamilies (35 genes) and
      2 IL17 receptors. Most of these subfamilies are conserved throughout echinoderms.
      Two IL17 subfamilies are sequentially strongly upregulated and attenuated in the
      gut epithelium in response to bacterial disturbance. IL17R1 signal perturbation
      results in reduced expression of several response genes including an IL17
      subtype, indicating a potential feedback. A third IL17 subfamily is activated in
      adult immune cells indicating that expression in immune cells and epithelia is
      divided among families. The larva provides a tractable model to investigate the
      regulation and consequences of gut epithelial IL17 expression across the
      organism.

PMID- 28447938
TI  - Low serum selenium concentrations in French patients with measles.
AB  - OBJECTIVE: Selenium deficiency adversely affects the clinical outcome of measles
      in the tropics. In developed countries, serum selenium level has never been
      investigated during acute measles. The aim of this study was to determine serum
      selenium concentrations in French patients with acute measles and to seek
      correlations with clinical and virological findings. PATIENTS AND METHODS: We
      studied serum selenium concentrations in 94 French patients with acute measles
      and in 99 healthy controls matched for age and sex. RESULTS: The mean of selenium
      concentration was significantly lower in the patients than in the controls
      (46.4+/-14.1MUg/L versus 86.5+/-13.9MUg/L, P<0.0001). In the patients, selenium
      concentrations were not associated with age, sex, vaccination status, clinical
      signs or specific antibody responses. Selenium levels did not differ
      significantly between patients with uncomplicated measles (45.8+/-14.2MUg/L) and
      patients with complications (52.7+/-13.2MUg/L) (P=0.15). CONCLUSION: Acute
      measles is associated with significant reduction of selenium level that did not
      seem to negatively affect the course of the disease suggesting compensating
      mechanisms in patients from developed countries against the disease.

PMID- 28447940
TI  - Is malaria elimination within reach?

PMID- 28447941
TI  - Keeping the faith-reporting on antimicrobial resistance in an era of fake news.

PMID- 28447939
TI  - A Progesterone-CXCR4 Axis Controls Mammary Progenitor Cell Fate in the Adult
      Gland.
AB  - Progesterone drives mammary stem and progenitor cell dynamics through paracrine
      mechanisms that are currently not well understood. Here, we demonstrate that
      CXCR4, the receptor for stromal-derived factor 1 (SDF-1; CXC12), is a crucial
      instructor of hormone-induced mammary stem and progenitor cell function.
      Progesterone elicits specific changes in the transcriptome of basal and luminal
      mammary epithelial populations, where CXCL12 and CXCR4 represent a putative
      ligand-receptor pair. In situ, CXCL12 localizes to progesterone-receptor-positive
      luminal cells, whereas CXCR4 is induced in both basal and luminal compartments in
      a progesterone-dependent manner. Pharmacological inhibition of CXCR4 signaling
      abrogates progesterone-directed expansion of basal (CD24+CD49fhi) and luminal
      (CD24+CD49flo) subsets. This is accompanied by a marked reduction in CD49b+SCA-1-
      luminal progenitors, their functional capacity, and lobuloalveologenesis. These
      findings uncover CXCL12 and CXCR4 as novel paracrine effectors of hormone
      signaling in the adult mammary gland, and present a new avenue for potentially
      targeting progenitor cell growth and malignant transformation in breast cancer.

PMID- 28447942
TI  - Corrections.

PMID- 28447943
TI  - Corrections.

PMID- 28447944
TI  - Corrections.

PMID- 28447945
TI  - Fighting antibiotic resistance is in your hands: May 5, 2017.

PMID- 28447946
TI  - Correction to global antibiotic consumption data.

PMID- 28447947
TI  - Outbreak reporting a decade after ORION: where do we stand?

PMID- 28447948
TI  - Staphylococcus aureus nasal carriage among medical students.

PMID- 28447949
TI  - Clostridium difficile in England: can we stop washing our hands? - Authors'
      reply.

PMID- 28447950
TI  - Clostridium difficile in England: can we stop washing our hands?

PMID- 28447951
TI  - Vaccination against cholera in Juba.

PMID- 28447952
TI  - Vaccination against cholera in Juba - Authors' reply.

PMID- 28447953
TI  - Short duration of direct-acting antivirals for acute HCV infection.

PMID- 28447954
TI  - Methodological concerns regarding a PrEP model.

PMID- 28447955
TI  - Methodological concerns regarding a PrEP model - Authors' reply.

PMID- 28447956
TI  - Outbreaks of chikungunya in Pakistan.

PMID- 28447957
TI  - Trevor Mundel: President of the Gates' Foundation Global Health Division.

PMID- 28447958
TI  - Mycoplasma-induced rash and mucositis in a young patient with red eyes, oral
      mucositis, and targetoid cutaneous vesicles.

PMID- 28447959
TI  - Using measurable dosimetric quantities to characterize the inter-structural
      tradeoff in inverse planning.
AB  - Traditional inverse planning relies on the use of weighting factors to balance
      the conflicting requirements of different structures. Manual trial-and-error
      determination of weighting factors has long been recognized as a time-consuming
      part of treatment planning. The purpose of this work is to develop an inverse
      planning framework that parameterizes the dosimetric tradeoff among the
      structures with physically meaningful quantities to simplify the search for
      clinically sensible plans. In this formalism, instead of using weighting factors,
      the permissible variation range of the prescription dose or dose volume histogram
      (DVH) of the involved structures are used to characterize the 'importance' of the
      structures. The inverse planning is then formulated into a convex feasibility
      problem, called the dosimetric variation-controlled model (DVCM), whose goal is
      to generate plans with dosimetric or DVH variations of the structures consistent
      with the pre-specified values. For simplicity, the dosimetric variation range for
      a structure is extracted from a library of previous cases which possess similar
      anatomy and prescription. A two-phase procedure (TPP) is designed to solve the
      model. The first phase identifies a physically feasible plan to satisfy the
      prescribed dosimetric variation, and the second phase automatically improves the
      plan in case there is room for further improvement. The proposed technique is
      applied to plan two prostate cases and two head-and-neck cases and the results
      are compared with those obtained using a conventional CVaR approach and with a
      moment-based optimization scheme. Our results show that the strategy is able to
      generate clinically sensible plans with little trial and error. In all cases, the
      TPP generates a very competitive plan as compared to those obtained using the
      alternative approaches. Particularly, in the planning of one of the head-and-neck
      cases, the TPP leads to a non-trivial improvement in the resultant dose
      distribution-the fractional volumes receiving a dose above 20 Gy for the spinal
      cord are reduced by more than 40% when compared to the alternative schemes, while
      maintaining the same PTV coverage. With physically more meaningful modeling of
      the inter-structural tradeoff, the reported technique enables us to substantially
      reduce the need for trial-and-error adjustment of the model parameters. The new
      formalism also opens new opportunities for incorporating prior knowledge to
      facilitate the treatment planning process.

PMID- 28447960
TI  - An analytical reconstruction model of the spread-out Bragg peak using laser
      accelerated proton beams.
AB  - With the development of laser technology, laser-driven proton acceleration
      provides a new method for proton tumor therapy. However, it has not been applied
      in practice because of the wide and decreasing energy spectrum of laser
      accelerated proton beams. In this paper, we propose an analytical model to
      reconstruct the spread-out Bragg peak (SOBP) using laser-accelerated proton
      beams. Firstly, we present a modified weighting formula for protons of different
      energies. Secondly, a theoretical model for the reconstruction of SOBPs with
      laser-accelerated proton beams has been built. It can quickly calculate the
      number of laser shots needed for each energy interval of the laser-accelerated
      protons. Finally, we show the 2D reconstruction results of SOBPs for laser
      accelerated proton beams and the ideal situation. The final results show that our
      analytical model can give an SOBP reconstruction scheme that can be used for
      actual tumor therapy.

PMID- 28447961
TI  - Does the preoperative prognostic nutritional index predict postoperative
      complications in patients with colorectal cancer who underwent curative
      resection?
AB  - AIM: Malnutrition is a common and very important issue in colorectal cancer
      patients.The immunological and nutritional status of these patients have been
      reported to be correlated with the postoperative complications.The prognostic
      nutritional index (PNI) is an effective and simple parameter, initially created
      to evaluate preoperative surgical risks. The aim of this study was to evaluate
      the predictive value of PNI in patients with colorectal cancer who underwent
      surgery. METHODS: One hundred eighty patients who underwent curative colorectal
      resections for colorectal cancer were included in this retrospective study.
      Demographic characteristics of the patients, biochemical parameters, intra
      operative findings, operation type, postoperative surgical complications, and PNI
      values were collected Results:The median PNI value was 44,4(range 19
      60,5).Receiver Operating Characteristics demonstrated that a value below 39,75
      was the optimal cut-off value for the prediction of major complications. The
      median PNI values were significantly lower in patients with major complications
      (Clavien-Dindo grade 3 to 5). CONCLUSION: The PNI can predict severe
      complications in patients with colorectal cancer who are undergoing primary tumor
      resection. Investigation of the nutritional status by using the PNI could be a
      useful approach for clinical follow-up. KEY WORDS: Colorectal, Nutritional index,
      Postoperative complications.

PMID- 28447962
TI  - MowA(r): A simple and economic way of monitoring chronic wounds outcome with your
      mobile devices.
AB  - The treatment of skin ulcers of the lower extremities is a difficult challenge
      for surgeons as demonstrated in the literature 1,2. Furthermore objective
      monitoring of skin ulcers represts an important necessity for the plastic surgeon
      who has to update the treatment over time. In the past we had to write about
      systems and applications designed to catalog and manage digital libraries 3, so
      we have gone looking for a system to catalog and manage date related skin in
      ulcers. I present an application for mobile devices that allows to calculate ,
      evaluate and analyze, the both surface area and tissue quality of skin ulcers m
      in a fast and practical way. The application is called "Mowa(r)"and it is
      available both for Apple and Android devices. Often we have to treat chronic
      injuries to the skin for several weeks and the evaluation needs to takes place in
      a periodic manner. An important problem for a surgeon, in the treatment of
      chronic wounds of the skin, is to evaluate the effectiveness of the cure in terms
      of "reduction of the lesion" and "quality of tissue". That is, it would be useful
      having s way to assess the size(area) of the wound an quality if tissues inside
      the lesion. This would make it objectively easier to measure the progress if the
      treatment in the past there have been many proposed systems 4-6. We tried in the
      past, to use theVisa-track system (smith & Nephew) with good outcomes, but this
      is limited because it can be used by a single patient at atime. The need to find
      a more affordable way led us to experience Mora application in our devices. This
      simple application allows, through a photograph, to quantify in quare centimeters
      the surface of the lesion. Furtermore Mowa(r) provides a system for detecting the
      fibrin percentage of granulation and necrotic tissue. The analysis of the chronic
      lesion of the skin is also completed by the insertion of the main characteristics
      of the qound, for esample, the exudate (in small quantities,moderate or a lot).
      The suspicion of infection, bleeding and the depth of the lesion. The application
      also offers a treatment algorithm based in the data entered and follows the EPUAP
      and NPUAP guidelines 7. Once the assessment of chronic skin lesion takes place,
      it is possible to produce a PDF or JPEG file with photography and the
      characteristics of the wound.The producted files can be shared via email. The use
      of this simple application is of interest to those surgeons who want a quick way
      to evaluate in size and percentage skin ulcers. The ability to store and search
      Ptients data in a fast and practice way is the strongest point of this
      application. Through this application you can monitor and compare both size and
      outcome of chronic wound over time, When using the applicatiom, if you want,
      there is need to include any sensitive information relates to the patients, No
      author has economic interest and financed by the the advertising of this
      application.

PMID- 28447963
TI  - Bifid median nerve and carpal tunnel syndrome: an uncommon anatomical variation.
AB  - Dear sir, one of the most common entrapment neuropathy syndromes in clinical
      practice is "Entrapment of median nerve in carpal tunnel" also called "Carpal
      tunnel syndrome (CTS)" (Aydin et al., 2007; Huisstede et al., 2010). This
      syndrome is caused by entrapment of the median nerve in the wrist (Preston and
      Shapiro, 2005) when the pressure increases in the carpal tunnel. A high division
      of the median nerve proximal to the carpal tunnel, also known as a bifid median
      nerve, is a rare anatomic variation that may be associated with CTS and with
      persistent median vessels (Lanz, 1977). This anatomic variation has an incidence
      of 0,8% to 2,3% in patients with CTS. Lanz (1977) has characterized this anatomic
      condition of the median nerve in the carpal tunnel. These anatomic variants have
      been classified into four groups: - Group 0: extraligamentous thenar branch
      (standard anatomy); - Group 1: variations of the course of the thenar branch; -
      Group 2: accessory branches at the distal portion of the carpal tunnel; - Group
      3: divided or duplicated median nerve inside the carpal tunnel; - Group 4:
      accessory branches proximal to the carpal tunnel. During dissection of the wrist
      performed for the treatment of a CTS under local anesthesia, we found an
      anatomical variation of the median nerve that was divided in two branches inside
      the carpal tunnel (Group 3 of Lanz Classification) and in which its radial branch
      passed through its own compartment. The two parts of the nerve seems to be
      unequal in size (Fig. 1). Moreover the nerve passed in carpal tunnel associated
      with a median artery, so we classified this variation in the group 3b of Lanz
      Classification (Fig. 2). The persistence of median artery coexisting with a bifid
      median nerve has been widely reported in surgical literature (Lanz, 1977; Barbe
      et al., 2005). Before surgical intervention clinical evaluation of patient and
      electrophysiological examination showed no differences compared to a non bifid
      median nerve entrapment syndrome. In conclusion the bifid median nerve may
      facilitate compression of median nerve in the carpal tunnel because of its
      increased cross sectional area even if it has no electrophysiological or clinical
      differential diagnosis in case of CTS. The aim of this letter is aware the
      physicians in order to borne in mind the possible presence of a median nerve
      variation during dissection of carpal tunnel in order to avoid the damage of this
      non common anatomical structures.

PMID- 28447964
TI  - A rare cause of acute gastrointestinal hemorrhage: ileal lipoma Case report.
AB  - : Primary small bowel tumors account for 1-6% of all Gastrointestinal (G.I.)
      tract malignancies. Among these pedunculated lipomas are unusual. We report a
      case of a 66-year-old male with a history of G.I. hemorrhage and acute anemia,
      negative upper and lower endoscopies and a pedunculated lipoma in distal ileum,
      revealed by CT enterography. The patient was successfully treated by open
      surgery. Patients with G.I. hemorrhage and negative upper and lower endoscopies
      need an accurate evaluation of small bowel. Multislice CT enterography or
      Magnetic Resonance enteroclysis/ enterography represent the fastest and more
      accurate tools to obtain an exhaustive evaluation of small bowel. In case of
      small bowel tumors this diagnostic procedures can show site and stage and can
      even suggest histological type of such neoplasms, with a significant impact in
      the surgical planning, avoiding time consuming surgical exploration. In this
      patient multislice TC enterography allowed a correct diagnosis of benign lipoma
      due to its radiological density and absence of infiltration of the intestinal
      wall and surrounding tissues. KEY WORDS: CT enterography, Gastrointestinal
      hemorrhage, Lipoma, Small bowel.

PMID- 28447965
TI  - Perspectives of using of "aseptic" drains for abdominal drainage.
AB  - AIM: Aim of the study was to evaluate the effectiveness of using different types
      of drain tubes to prevent and reduce the drain-associated infection rate of
      abdominal drainage procedures. MATERIALS AND METHODS: 80 cases of used so called
      "standard", "coladerm" and "chlorhexidine" drain tubes for abdominal drainage
      were analysed. "Standard" drain tubes were used 35 times and "coladerm" and
      "chlorhexidine" tubes - 20 and 25 times respectively. There were adopted in
      different elective and emergency so called "clean", "potentially contaminated"
      and "contaminated" abdominal surgical procedures. The drain tubes were removed
      between 2 to 14 days after the operations followed by the bacteriological study
      in search of bacteria growth on the surface of drainage tubes were examined.
      RESULTS: Of all 35 cases of used "standard" drain tubes the bacterial growth was
      found in 23 cases, that means 65,7%; of 20 cases of drains covered by "coladerm"
      polymer the bacterial growth was found in 6 cases (30%) and only in 3 cases of 25
      cases of drain tubes covered by polymer and "chlorhexidine" were positive, that
      means 12%. The most interesting data were obtained considering the so called
      "clean" and "contaminated" operations. After the so called "clean" operations the
      bacterial growth using "standard" drain tubes was found almost in 50% of cases
      and in 8,3% of cases using "chlorhexidine" drain tubes. After the "potentially
      contaminated" and "contaminated" operations the bacterial growth was found in
      68,2% using "standard" tubes, and using "coladerm" and "chlorhexidine" drain
      tubes - in 50% and 16,7% respectively. CONCLUSIONS: In our limited experience
      using of new antimicrobial polymeric composites as coatings mean the adhesion of
      bacteria and formation of biofilm at drainage tubes is prevented, which can
      significantly reduce the drain-associated infection rate. KEY WORDS: Abdominal
      drainage, Bacterial growth, Infection rate.

PMID- 28447966
TI  - The prognostic value of preoperative PET/CT evaluation of maximum standardized
      uptake value in renal cell carcinomas.
AB  - AIM: The use of positron emission tomography (PET/CT) in kidney tumors has
      increased greatly in recent years. There have been few studies on the effect of
      SUVmax values detected by PET/CT on the mortality and survival estimation in
      patients with kidney tumors. In this study, it is hoped to contribute to the
      literature of research on survival and mortality estimations of kidney tumour
      patients through an evaluation of SUVmax values measured with PET/CT scan.
      MATERIAL AND METHODS: A retrospective review was made of the files of 21 patients
      newly-diagnosed with kidney tumor and with disease staging determined with PET/CT
      in the Nuclear medicine Department of Saglik Bilimleri University Diyarbakir Gazi
      Yasargil Training and Research Hospital between August 2007 and April 2012. The
      largest tumor seen on CT was considered as the tumour size and was stated in cm.
      The survival time was defined as the time from the date of PET/CT Imaging, which
      was taken into consideration while calculating the survival, and the date of
      death received from MERNIS (The Central Civil Registration System) or the final
      application date if the patient was alive. RESULTS: The lower the SUVmax value in
      the kidney tumour, the longer the survival time. The mortality risk of male
      patients was 12-fold higher than females and mortality increased 4-fold when
      SUVmax values were >= 4.5.Patients with a tumour on the right kidney had a longer
      survival time. With increasedage,survival time decreased. The SUVmax values and
      tumor size measured in left kidney tumors were higher than those measured in
      right kidney tumors. CONCLUSIONS: In the present study, it was concluded that the
      lower the SUVmax values and the smaller the tumour size, the longer the survival
      time. Mortality rates increased when SUVmax values were >= 4.5 (p=0.001).The use
      of PET/CT scan can be considered to contribute to mortality and survival
      estimations in patients with kidney tumor. KEY WORD: FDG, Renal cell Carcinoma,
      SUVmax.

PMID- 28447967
TI  - Management of colovesical and colovaginal diverticular fistulas Our experience
      and literature reviewed.
AB  - AIM: This study aims evaluate the effectiveness of various surgical techniques in
      treating diverticular fistulas, and the safety and efficacy of the laparoscopic
      procedure comparing our results with those of the literature. MATERIAL OF STUDY:
      This was a prospective and uncontrolled study performed at a general surgery
      units. Between 2005 and 2011, 16 patients (11 men, 5 women) underwent surgery for
      diverticular fistulas. The mean age was 70.2 (range, 35-87) years. The medical
      evaluation of these patients was based on symptoms and diagnostic procedures
      confirming the diagnosis of diverticular fistulas. Our surgical options included
      one-stage, two-stage, and defunctioning procedures. RESULTS: Out of 16 cases of
      diverticular fistula 14 were colovesical and 2 colovaginal. One-stage procedure
      was performed in 12 patients, two-stage procedure in 3 and defunctioning
      colostomy in 1. The overall complication rate was 31.2%. We recorded 1
      colovesical recurrent fistula. The laparoscopic surgery was performed in 4
      patients, nobody was converted to open and there were no post-operative
      complications and recurrence. DISCUSSION AND CONCLUSIONS: The data show that one
      stage procedure is effective in the majority of cases of diverticular fistulas.
      However, the surgery of colovesical and colovaginal fistulas is often associated
      to high complication rates. This is often due to the shoddy clinical conditions
      and long-term diverticular illness of this group of patients. At present, the
      laparoscopy in an elective setting is not considered any more a contraindication
      in the treatment of diverticular fistulas. KEY WORDS: Diverticular fistulas,
      Laparoscopic surgery.

PMID- 28447968
TI  - Protective effects of ursodeoxycholic acid in experimental corrosive esophagitis
      injury in rats.
AB  - : Accidental caustic ingestions are serious medical problems especially in
      childhood. Various treatment modalities are being used for the complications of
      caustic injuries such as stricture formation. The aim of this study is to
      establish whether ursodeoxycholic acid (UDCA) has protective effects on
      experimental corrosive esophagitis in rats. Twenty four Wistar-albino rats,
      weighing 220-240 g, were used in the study. Experimental animals were divided in
      three groups randomly: UDCA treatment group (Group T, n:8), control group (Group
      K, n: 8) and sham group (Group S, n: 8). In group T and S corrosive esophagitis
      was induced. UDCA (5 mg/kg) was performed to the group T for 10 days orally. All
      animals were sacrificed at the end of procedures and histopathological changes in
      esophageal tissue were scored by a single investigator who was blind to the
      groups. In group T inflammation was present in two rats, muscularis mucosa injury
      in two rats, grade 1 collagen deposition in six rats and grade 2 in two rats. In
      comparison with group S these were statistically significant (p value was 0.003,
      0.003 and 0.015, respectively). UDCA has protective effect in experimental
      corrosive esophagitis. KEY WORDS: Corrosive esophagitis, Rat, Stricture,
      Ursodeoxycholic acid.

PMID- 28447969
TI  - Multicomponent compression stockings in chronic venous leg ulcer treatment A
      review of the current literature.
AB  - : The role of compression stockings in the treatment of chronic venous disease
      was amply demonstrated. Concerning patients with chronic venous leg ulcers
      (VLUs), multi-layer bandage is the standard of care. Recently, multicomponent
      compression stocking (McCS) systems for VLUs treatment and healing nowaday have
      been proposed. The aim of this review is to describe and analyze current
      literature evidence regarding McCS used in VLUs treatment. KEY WORDS: Compression
      therapy, Compression stockings, Venous leg ulcers.

PMID- 28447970
TI  - Laparoscopic recurrent inguinal hernia repair during the learning curve: it can
      be done?
AB  - AIM: Trans-Abdominal Preperitoneal Patch (TAPP) repairs for Recurrent Hernia (RH)
      is a technically demanding procedure. It has to be performed only by surgeons
      with extensive experience in the laparoscopic approach. The purpose of this study
      is to evaluate the surgical safety and the efficacy of TAPP for RH performed in a
      tutoring program by surgeons in practice (SP). MATERIAL AND STUDY: All TAPP
      repairs for RH performed by the same surgical team have been included in the
      study. We have evaluated the results of three SP during their learning curve in a
      tutoring program. Then these results have been compared to those of a highly
      experienced laparoscopic surgeon (Benchmark). RESULTS: A total of 530 TAPP
      repairs have been performed. Among these, 83 TAPP have been executed for RH, of
      which 43 by the Benchmark and 40 by the SP. When we have compared the outcomes of
      the Benchmark with those of SP, no significant difference has been observed about
      morbidity and recurrence while the operative time has been significantly longer
      for the SP. No intraoperative complications have occurred. DISCUSSION:
      International guidelines urge that TAPP repair for RH has to be performed only by
      surgeons with extensive experience in the laparoscopic approach. The results of
      the present study demonstrate that TAPP for RH could be performed also by
      surgeons in training during a learning program. CONCLUSIONS: We retain that an
      adequate tutoring program could lead a surgeon in practice to perform more
      complex hernia procedures without jeopardizing patient safety throughout the
      learning curve period. KEY WORDS: Laparoscopy, Learning Curve, Recurrent Hernia.

PMID- 28447971
TI  - The Local and Systemic Inflammatory Response in a Pig Burn Wound Model With a
      Pivotal Role for Complement.
AB  - In patients with burns, a massive inflammatory response is induced which
      negatively affects the healing process of the burn wound and additionally exerts
      systemic effects. An important factor herein is the complement system. Here we
      analyzed the effects of burns on complement and inflammatory cells both locally
      and systemically after burn in time in a pig burn wound model. In burned pigs,
      burn wound biopsies and blood were collected up to 60 days after burn. Complement
      in blood as well as complement and inflammatory cells in the burn wound and
      several organs were determined. In the blood, C3 was significantly increased
      after 9 to 60 days, whereas C4 after 21 to 30 days after burn. In the burn wound,
      C3 levels were significantly increased after 9 days and C4 after 3 days,
      whereafter both declined after 21 and 9 days, respectively. Neutrophils,
      macrophages, and lymphocytes were significantly increased in the burn wound after
      3 days, all declined after 21 days after burn. In the heart, at 60 days after
      burn, an increase of neutrophils and macrophages was observed, mainly in the
      right atrium. In contrast to the heart, the inflammatory cell infiltrates in the
      lungs, liver, and kidney of burned pigs were lower than in control pigs. In pigs,
      following burn there is a prolonged increase in complement levels both in the
      burn wound and the blood and increased inflammatory cell infiltrate in the burn
      wound and the heart. However, complement levels in the burn wound and in the
      blood seem not to be correlated in time.

PMID- 28447972
TI  - Wild-type Blocking PCR Combined with Direct Sequencing as a Highly Sensitive
      Method for Detection of Low-Frequency Somatic Mutations.
AB  - Accurate detection and identification of low frequency mutations can be
      problematic when assessing residual disease after therapy, screening for emerging
      resistance mutations during therapy, or when patients have few circulating tumor
      cells. Wild-type blocking PCR followed by sequencing analysis offers high
      sensitivity, flexibility, and simplicity as a methodology for detecting these low
      frequency mutations. By adding a custom designed locked nucleic acid
      oligonucleotide to a new or previously established conventional PCR based
      sequencing assay, sensitivities of approximately 1 mutant allele in a background
      of 1,000 WT alleles can be achieved (1:1,000). Sequencing artifacts associated
      with deamination events commonly found in formalin fixed paraffin embedded
      tissues can be partially remedied by the use of uracil DNA glycosylase during
      extraction steps. The optimized protocol here is specific for detecting MYD88
      mutation, but can serve as a template to design any WTB-PCR assay. Advantages of
      the WTB-PCR assay over other commonly utilized assays for the detection of low
      frequency mutations including allele specific PCR and real-time quantitative PCR
      include fewer occurrences of false positives, greater flexibility and ease of
      implementation, and the ability to detect both known and unknown mutations.

PMID- 28447973
TI  - Methods to Study Lipid Alterations in Neutrophils and the Subsequent Formation of
      Neutrophil Extracellular Traps.
AB  - Lipid analysis performed by high performance thin layer chromatography (HPTLC) is
      a relatively simple, cost-effective method of analyzing a broad range of lipids.
      The function of lipids (e.g., in host-pathogen interactions or host entry) has
      been reported to play a crucial role in cellular processes. Here, we show a
      method to determine lipid composition, with a focus on the cholesterol level of
      primary blood-derived neutrophils, by HPTLC in comparison to high performance
      liquid chromatography (HPLC). The aim was to investigate the role of
      lipid/cholesterol alterations in the formation of neutrophil extracellular traps
      (NETs). NET release is known as a host defense mechanism to prevent pathogens
      from spreading within the host. Therefore, blood-derived human neutrophils were
      treated with methyl-beta-cyclodextrin (MbetaCD) to induce lipid alterations in
      the cells. Using HPTLC and HPLC, we have shown that MbetaCD treatment of the
      cells leads to lipid alterations associated with a significant reduction in the
      cholesterol content of the cell. At the same time, MbetaCD treatment of the
      neutrophils led to the formation of NETs, as shown by immunofluorescence
      microscopy. In summary, here we present a detailed method to study lipid
      alterations in neutrophils and the formation of NETs.

PMID- 28447974
TI  - 3D Whole-heart Myocardial Tissue Analysis.
AB  - Cardiac regenerative therapies aim to protect and repair the injured heart in
      patients with ischemic heart disease. By injecting stem cells or other
      biologicals that enhance angio- or vasculogenesis into the infarct border zone
      (IBZ), tissue perfusion is improved, and the myocardium can be protected from
      further damage. For maximum therapeutic effect, it is hypothesized that the
      regenerative substance is best delivered to the IBZ. This requires accurate
      injections and has led to the development of new injection techniques. To
      validate these new techniques, we have designed a validation protocol based on
      myocardial tissue analysis. This protocol includes whole-heart myocardial tissue
      processing that enables detailed two-dimensional (2D) and three-dimensional (3D)
      analysis of the cardiac anatomy and intramyocardial injections. In a pig,
      myocardial infarction was created by a 90-min occlusion of the left anterior
      descending coronary artery. Four weeks later, a mixture of a hydrogel with
      superparamagnetic iron oxide particles (SPIOs) and fluorescent beads was injected
      in the IBZ using a minimally-invasive endocardial approach. 1 h after the
      injection procedure, the pig was euthanized, and the heart was excised and
      embedded in agarose (agar). After the solidification of the agar, magnetic
      resonance imaging (MRI), slicing of the heart, and fluorescence imaging were
      performed. After image post-processing, 3D analysis was performed to assess the
      IBZ targeting accuracy. This protocol provides a structured and reproducible
      method for the assessment of the targeting accuracy of intramyocardial injections
      into the IBZ. The protocol can be easily used when the processing of scar tissue
      and/or validation of the injection accuracy of the whole heart is desired.

PMID- 28447975
TI  - Measurement of Quantum Interference in a Silicon Ring Resonator Photon Source.
AB  - Silicon photonic chips have the potential to realize complex integrated quantum
      information processing circuits, including photon sources, qubit manipulation,
      and integrated single-photon detectors. Here, we present the key aspects of
      preparing and testing a silicon photonic quantum chip with an integrated photon
      source and two-photon interferometer. The most important aspect of an integrated
      quantum circuit is minimizing loss so that all of the generated photons are
      detected with the highest possible fidelity. Here, we describe how to perform low
      loss edge coupling by using an ultra-high numerical aperture fiber to closely
      match the mode of the silicon waveguides. By using an optimized fusion splicing
      recipe, the UHNA fiber is seamlessly interfaced with a standard single-mode
      fiber. This low-loss coupling allows the measurement of high-fidelity photon
      production in an integrated silicon ring resonator and the subsequent two-photon
      interference of the produced photons in a closely integrated Mach-Zehnder
      interferometer. This paper describes the essential procedures for the preparation
      and characterization of high-performance and scalable silicon quantum photonic
      circuits.

PMID- 28447976
TI  - Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp
      Model.
AB  - Major hepatic surgery with inflow occlusion, and liver transplantation,
      necessitate a period of warm ischemia, and a period of reperfusion leading to
      ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential
      I/R injury in marginal organs destined for liver transplantation contributes to
      the current donor shortage secondary to a decreased organ utilization rate. A
      significant need exists to explore hepatic I/R injury in order to mediate its
      impact on graft function in transplantation. Rat liver hilar clamp models are
      used to investigate the impact of different molecules on hepatic I/R injury.
      Depending on the model, these molecules have been delivered using inhalation,
      epidural infusion, intraperitoneal injection, intravenous administration or
      injection into the peripheral superior mesenteric vein. A rat liver hilar clamp
      model has been developed for use in studying the impact of pharmacologic
      molecules in ameliorating I/R injury. The described model for rat liver hilar
      clamp includes direct cannulation of the portal supply to the ischemic hepatic
      segment via a side branch of the portal vein, allowing for direct segmental
      hepatic delivery. Our approach is to induce ischemia in the left lateral and
      median lobes for 60 min, during which time the substance under study is infused.
      In this case, pegylated-superoxide dismutase (PEG-SOD), a free radical scavenger,
      is infused directly into the ischemic segment. This series of experiments
      demonstrates that infusion of PEG-SOD is protective against hepatic I/R injury.
      Advantages of this approach include direct injection of the molecule into the
      ischemic segment with consequent decrease in volume of distribution and reduction
      in systemic side effects.

PMID- 28447977
TI  - Plasmonic Trapping and Release of Nanoparticles in a Monitoring Environment.
AB  - Plasmonic tweezers use surface plasmon polaritons to confine polarizable
      nanoscale objects. Among the various designs of plasmonic tweezers, only a few
      can observe immobilized particles. Moreover, a limited number of studies have
      experimentally measured the exertable forces on the particles. The designs can be
      classified as the protruding nanodisk type or the suppressed nanohole type. For
      the latter, microscopic observation is extremely challenging. In this paper, a
      new plasmonic tweezer system is introduced to monitor particles, both in
      directions parallel and orthogonal to the symmetric axis of a plasmonic nanohole
      structure. This feature enables us to observe the movement of each particle near
      the rim of the nanohole. Furthermore, we can quantitatively estimate the maximal
      trapping forces using a new fluidic channel.

PMID- 28447978
TI  - High-resolution Thermal Micro-imaging Using Europium Chelate Luminescent
      Coatings.
AB  - Micro-electronic devices often undergo significant self-heating when biased to
      their typical operating conditions. This paper describes a convenient optical
      micro-imaging technique which can be used to map and quantify such behavior.
      Europium thenoyltrifluoroacetonate (EuTFC) has a 612 nm luminescence line whose
      activation efficiency drops strongly with increasing temperature, due to T
      dependent interactions between the Eu3+ ion and the organic chelating compound.
      This material may be readily coated on to a sample surface by thermal sublimation
      in vacuum. When the coating is excited with ultraviolet light (337 nm) an optical
      micro-image of the 612 nm luminescent response can be converted directly into a
      map of the sample surface temperature. This technique offers spatial resolution
      limited only by the microscope optics (about 1 micron) and time resolution
      limited by the speed of the camera employed. It offers the additional advantages
      of only requiring comparatively simple and non-specialized equipment, and giving
      a quantitative probe of sample temperature.

PMID- 28447979
TI  - Reconstitution of Nucleosomes with Differentially Isotope-labeled Sister
      Histones.
AB  - Asymmetrically modified nucleosomes contain the two copies of a histone (sister
      histones) decorated with distinct sets of Post-translational Modifications
      (PTMs). They are newly identified species with unknown means of establishment and
      functional implications. Current analytical methods are inadequate to detect the
      copy-specific occurrence of PTMs on the nucleosomal sister histones. This
      protocol presents a biochemical method for the in vitro reconstitution of
      nucleosomes containing differentially isotope-labeled sister histones. The
      generated complex can be also asymmetrically modified, after including a
      premodified histone pool during refolding of histone subcomplexes. These
      asymmetric nucleosome preparations can be readily reacted with histone-modifying
      enzymes to study modification cross-talk mechanisms imposed by the asymmetrically
      pre-incorporated PTM using nuclear magnetic resonance (NMR) spectroscopy.
      Particularly, the modification reactions in real-time can be mapped independently
      on the two sister histones by performing different types of NMR correlation
      experiments, tailored for the respective isotope type. This methodology provides
      the means to study crosstalk mechanisms that contribute to the formation and
      propagation of asymmetric PTM patterns on nucleosomal complexes.

PMID- 28447980
TI  - Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small
      Animals.
AB  - Development of new therapeutic products requires efficacy testing in an animal
      model. The pulmonary route of administration can be utilized to deliver drugs
      locally and systemically. Evaluation of dry powder aerosols necessitates an
      efficient dispersion mechanism to maintain high concentrations in an exposure
      chamber or for direct endotracheal administration. While solutions exist to
      expose animals by passive inhalation to dry powder aerosols, most require masses
      of powder in large excess of the dose delivered. This precludes conducting early
      feasibility studies as insufficient drug is available at the research or early
      development stage to support the dose delivery requirements for conventional
      aerosol delivery systems. When designing an aerosol drug product, aerodynamic
      performance can relate directly to delivery efficiency and efficacy. Dispersion
      of powder into an aerosol requires energy input sufficient to overcome
      interparticulate forces, and particle engineering approaches can substantially
      improve aerosol performance. We have developed a dispersion system (dosator)
      which can aerosolize engineered dry powder aerosols efficiently for the purpose
      of direct pulmonary insufflation, dispersion into an exposure system or
      generation for analytical purposes.

PMID- 28447981
TI  - Isolation, Characterization, and Purification of Macrophages from Tissues
      Affected by Obesity-related Inflammation.
AB  - Obesity promotes a chronic inflammatory state that is largely mediated by tissue
      resident macrophages as well as monocyte-derived macrophages. Diet-induced
      obesity (DIO) is a valuable model in studying the role of macrophage
      heterogeneity; however, adequate macrophage isolations are difficult to acquire
      from inflamed tissues. In this protocol, we outline the isolation steps and
      necessary troubleshooting guidelines derived from our studies for obtaining a
      suitable population of tissue-resident macrophages from mice following 18 weeks
      of high-fat (HFD) or high-fat/high-cholesterol (HFHCD) diet intervention. This
      protocol focuses on three hallmark tissues studied in obesity and atherosclerosis
      including the liver, white adipose tissues (WAT), and the aorta. We highlight how
      dualistic usage of flow cytometry can achieve a new dimension of isolation and
      characterization of tissue-resident macrophages. A fundamental section of this
      protocol addresses the intricacies underlying tissue-specific enzymatic
      digestions and macrophage isolation, and subsequent cell-surface antibody
      staining for flow cytometric analysis. This protocol addresses existing
      complexities underlying fluorescent-activated cell sorting (FACS) and presents
      clarifications to these complexities so as to obtain broad range characterization
      from adequately sorted cell populations. Alternate enrichment methods are
      included for sorting cells, such as the dense liver, allowing for flexibility and
      time management when working with FACS. In brief, this protocol aids the
      researcher to evaluate macrophage heterogeneity from a multitude of inflamed
      tissues in a given study and provides insightful troubleshooting tips that have
      been successful for favorable cellular isolation and characterization of immune
      cells in DIO-mediated inflammation.

PMID- 28447982
TI  - Evaluating the Effect of Environmental Chemicals on Honey Bee Development from
      the Individual to Colony Level.
AB  - The presence of pesticides in the beekeeping environment is one of the most
      serious problems that impacts the life of a honey bee. Pesticides can be brought
      back to the beehive after the bees have foraged on flowers that have been sprayed
      with pesticides. Pesticide contaminated food can be exchanged between workers
      which then feed larvae and therefore can potentially affect the development of
      honey bees. Thus, residual pesticides in the environment can become a chronic
      damaging factor to honey bee populations and gradually lead to colony collapse.
      In the presented protocol, honey bee feeding methods are described and applied to
      either an individual honey bee or to a colony. Here, the insect growth regulator
      (IGR) pyriproxyfen (PPN), which is widely used to control pest insects and is
      harmful to the development of honey bee larvae and pupae, is used as the
      pesticide. The presenting procedure can be applied to other potentially harmful
      chemicals or honeybee pathogens for further studies.

PMID- 28447983
TI  - High Temperature Fabrication of Nanostructured Yttria-Stabilized-Zirconia (YSZ)
      Scaffolds by In Situ Carbon Templating Xerogels.
AB  - We demonstrate a method for the high temperature fabrication of porous,
      nanostructured yttria-stabilized-zirconia (YSZ, 8 mol% yttria - 92 mol% zirconia)
      scaffolds with tunable specific surface areas up to 80 m2.g-1. An aqueous
      solution of a zirconium salt, yttrium salt, and glucose is mixed with propylene
      oxide (PO) to form a gel. The gel is dried under ambient conditions to form a
      xerogel. The xerogel is pressed into pellets and then sintered in an argon
      atmosphere. During sintering, a YSZ ceramic phase forms and the organic
      components decompose, leaving behind amorphous carbon. The carbon formed in situ
      serves as a hard template, preserving a high surface area YSZ nanomorphology at
      sintering temperature. The carbon is subsequently removed by oxidation in air at
      low temperature, resulting in a porous, nanostructured YSZ scaffold. The
      concentration of the carbon template and the final scaffold surface area can be
      systematically tuned by varying the glucose concentration in the gel synthesis.
      The carbon template concentration was quantified using thermogravimetric analysis
      (TGA), the surface area and pore size distribution was determined by physical
      adsorption measurements, and the morphology was characterized using scanning
      electron microscopy (SEM). Phase purity and crystallite size was determined using
      X-ray diffraction (XRD). This fabrication approach provides a novel, flexible
      platform for realizing unprecedented scaffold surface areas and nanomorphologies
      for ceramic-based electrochemical energy conversion applications, e.g. solid
      oxide fuel cell (SOFC) electrodes.

PMID- 28447984
TI  - Experience is Instrumental in Tuning a Link Between Language and Cognition:
      Evidence from 6- to 7- Month-Old Infants' Object Categorization.
AB  - At birth, infants not only prefer listening to human vocalizations, but also have
      begun to link these vocalizations to cognition: For infants as young as three
      months of age, listening to human language supports object categorization, a core
      cognitive capacity. This precocious link is initially broad: At 3 and 4 months,
      vocalizations of both humans and nonhuman primates support categorization. But by
      6 months, infants have narrowed the link: Only human vocalizations support object
      categorization. Here we ask what guides infants as they tune their initially
      broad link to a more precise one, engaged only by the vocalizations of our
      species. Across three studies, we use a novel exposure paradigm to examine the
      effects of experience. We document that merely exposing infants to nonhuman
      primate vocalizations enables infants to preserve the early-established link
      between this signal and categorization. In contrast, exposing infants to backward
      speech - a signal that fails to support categorization at any age - offers no
      such advantage. Our findings reveal the power of early experience as infants
      specify which signals, from an initially broad set, they will continue to link to
      cognition.

PMID- 28447985
TI  - Methods for the Self-integration of Megamolecular Biopolymers on the Drying Air
      LC Interface.
AB  - Living organisms that use water are always prone to drying in the environment.
      Their activities are driven by biopolymer-based micro- and macro-structures, as
      seen in the cases of moving water in vascular bundles and moisturizing water in
      skin layers. In this study, we developed a method for assessing the effect of
      aqueous liquid crystalline (LC) solutions composed of biopolymers on drying. As
      LC biopolymers have megamolecular weight, we chose to study polysaccharides,
      cytoskeletal proteins, and DNA. The observation of biopolymer solutions during
      drying under polarized light reveals milliscale self-integration starting from
      the unstable air-LC interface. The dynamics of the aqueous LC biopolymer
      solutions can be monitored by evaporating water from a one-side-open cell. By
      analyzing the images taken using cross-polarized light, it is possible to
      recognize the spatio-temporal changes in the orientational order parameter. This
      method can be useful for the characterization of not only artificial materials in
      various fields, but also natural living tissues. We believe that it will provide
      an evaluation method for soft materials in the biomedical and environmental
      fields.

PMID- 28447986
TI  - Resolving Affinity Purified Protein Complexes by Blue Native PAGE and Protein
      Correlation Profiling.
AB  - Most proteins act in association with others; hence, it is crucial to
      characterize these functional units in order to fully understand biological
      processes. Affinity purification coupled to mass spectrometry (AP-MS) has become
      the method of choice for identifying protein-protein interactions. However,
      conventional AP-MS studies provide information on protein interactions, but the
      organizational information is lost. To address this issue, we developed a
      strategy to unravel the distinct functional assemblies a protein might be
      involved in, by resolving affinity-purified protein complexes prior to their
      characterization by mass spectrometry. Protein complexes isolated through
      affinity purification of a bait protein using an epitope tag and competitive
      elution are separated through blue native electrophoresis. Comparison of protein
      migration profiles through correlation profiling using quantitative mass
      spectrometry allows assignment of interacting proteins to distinct molecular
      entities. This method is able to resolve protein complexes of close molecular
      weights that might not be resolved by traditional chromatographic techniques such
      as gel filtration. With little more work than conventional AP-geLC-MS/MS, we
      demonstrate this strategy may in many cases be adequate for obtaining protein
      complex topological information concomitantly to identifying protein
      interactions.

PMID- 28447987
TI  - Live Cell Imaging and 3D Analysis of Angiotensin Receptor Type 1a Trafficking in
      Transfected Human Embryonic Kidney Cells Using Confocal Microscopy.
AB  - Live-cell imaging is used to simultaneously capture time-lapse images of
      angiotensin type 1a receptors (AT1aR) and intracellular compartments in
      transfected human embryonic kidney-293 (HEK) cells following stimulation with
      angiotensin II (Ang II). HEK cells are transiently transfected with plasmid DNA
      containing AT1aR tagged with enhanced green fluorescent protein (EGFP). Lysosomes
      are identified with a red fluorescent dye. Live-cell images are captured on a
      laser scanning confocal microscope after Ang II stimulation and analyzed by
      software in three dimensions (3D, voxels) over time. Live-cell imaging enables
      investigations into receptor trafficking and avoids confounds associated with
      fixation, and in particular, the loss or artefactual displacement of EGFP-tagged
      membrane receptors. Thus, as individual cells are tracked through time, the
      subcellular localization of receptors can be imaged and measured. Images must be
      acquired sufficiently rapidly to capture rapid vesicle movement. Yet, at faster
      imaging speeds, the number of photons collected is reduced. Compromises must also
      be made in the selection of imaging parameters like voxel size in order to gain
      imaging speed. Significant applications of live-cell imaging are to study protein
      trafficking, migration, proliferation, cell cycle, apoptosis, autophagy and
      protein-protein interaction and dynamics, to name but a few.

PMID- 28447988
TI  - Increased Recovery Time and Decreased LPS Administration to Study the Vagus Nerve
      Stimulation Mechanisms in Limited Inflammatory Responses.
AB  - Inflammation is a local response to infection and tissue damage mediated by
      activated macrophages, monocytes, and other immune cells that release cytokines
      and other mediators of inflammation. For a long time, humoral and cellular
      mechanisms have been studied for their role in regulating the immune response,
      but recent advances in the field of immunology and neuroscience have also
      unraveled specific neural mechanisms with interesting therapeutic potential. The
      so-called cholinergic anti-inflammatory pathway (CAP) has been described to
      control innate immune responses and inflammation in a very potent manner. In the
      early 2000s, Tracey and collaborators developed a technique that stimulates the
      vagus nerve and mimics the effect of the pathway. The methodology is based on the
      electrical stimulation of the vagus nerve at low voltage and frequency, in order
      to avoid any side effects of overstimulation, such as deregulation of heart rate
      variability. Electrical devices for stimulation are now available, making it easy
      to set up the methodology in the laboratory. The goal of this research was to
      investigate the potential involvement of prostaglandins in the CAP.
      Unfortunately, based on earlier attempts, we failed to use the original protocol,
      as the induced inflammatory response either was too high or was not suitable for
      enzymatic metabolism properties. The different settings of the original surgery
      protocol remained mostly unchanged, but the conditions regarding inflammatory
      induction and the time point before sacrifice were improved to fit our purposes
      (i.e., to investigate the involvement of the CAP in more limited inflammatory
      responses). The modified version of the original protocol, presented here,
      includes a longer time range between vagus nerve stimulation and analysis, which
      is associated with a lower induction of inflammatory responses. Additionally,
      while decreasing the level of lipopolysaccharides (LPS) to inject, we also came
      across new observations regarding mechanistic properties in the spleen.

PMID- 28447990
TI  - Imaging Neurons within Thick Brain Sections Using the Golgi-Cox Method.
AB  - The Golgi-Cox method of neuron staining has been employed for more than two
      hundred years to advance our understanding of neuron morphology within
      histological brain samples. While it is preferable from a practical perspective
      to prepare brain sections at the greatest thickness possible, in order to
      increase the probability of identifying stained neurons that are fully contained
      within single sections, this approach is limited from a technical perspective by
      the working distance of high-magnification microscope objectives. We report here
      a protocol to stain neurons using the Golgi-Cox method in mouse brain sections
      that are cut at 500 MUm thickness, and to visualize neurons throughout the depth
      of these sections using an upright microscope fitted with a high-resolution 30X
      1.05 N.A. silicone oil-immersion objective that has an 800 MUm working distance.
      We also report two useful variants of this protocol that may be employed to
      counterstain the surface of mounted brain sections with the cresyl violet Nissl
      stain, or to freeze whole brains for long-term storage prior to sectioning and
      final processing. The main protocol and its two variants produce stained thick
      brain sections, throughout which full neuron dendritic trees and dendrite spines
      may be reliably visualized and quantified.

PMID- 28447989
TI  - Fabrication of Extracellular Matrix-derived Foams and Microcarriers as Tissue
      specific Cell Culture and Delivery Platforms.
AB  - Cell function is mediated by interactions with the extracellular matrix (ECM),
      which has complex tissue-specific composition and architecture. The focus of this
      article is on the methods for fabricating ECM-derived porous foams and
      microcarriers for use as biologically-relevant substrates in advanced 3D in vitro
      cell culture models or as pro-regenerative scaffolds and cell delivery systems
      for tissue engineering and regenerative medicine. Using decellularized tissues or
      purified insoluble collagen as a starting material, the techniques can be applied
      to synthesize a broad array of tissue-specific bioscaffolds with customizable
      geometries. The approach involves mechanical processing and mild enzymatic
      digestion to yield an ECM suspension that is used to fabricate the three
      dimensional foams or microcarriers through controlled freezing and lyophilization
      procedures. These pure ECM-derived scaffolds are highly porous, yet stable
      without the need for chemical crosslinking agents or other additives that may
      negatively impact cell function. The scaffold properties can be tuned to some
      extent by varying factors such as the ECM suspension concentration, mechanical
      processing methods, or synthesis conditions. In general, the scaffolds are robust
      and easy to handle, and can be processed as tissues for most standard biological
      assays, providing a versatile and user-friendly 3D cell culture platform that
      mimics the native ECM composition. Overall, these straightforward methods for
      fabricating customized ECM-derived foams and microcarriers may be of interest to
      both biologists and biomedical engineers as tissue-specific cell-instructive
      platforms for in vitro and in vivo applications.

PMID- 28447991
TI  - Isolation and Characterization of Mesenchymal Stromal Cells from Human Umbilical
      Cord and Fetal Placenta.
AB  - The human umbilical cord (UC) and placenta are non-invasive, primitive and
      abundant sources of mesenchymal stromal cells (MSCs) that have increasingly
      gained attention because they do not pose any ethical or moral concerns. Current
      methods to isolate MSCs from UC yield low amounts of cells with variable
      proliferation potentials. Since UC is an anatomically-complex organ, differences
      in MSC properties may be due to the differences in the anatomical regions of
      their isolation. In this study, we first dissected the cord/placenta samples into
      three discrete anatomical regions: UC, cord-placenta junction (CPJ), and fetal
      placenta (FP). Second, two distinct zones, cord lining (CL) and Wharton's jelly
      (WJ), were separated. The explant culture technique was then used to isolate
      cells from the four sources. The time required for the primary culture of cells
      from the explants varied depending on the source of the tissue. Outgrowth of the
      cells occurred within 3 - 4 days of the CPJ explants, whereas growth was observed
      after 7 - 10 days and 11 - 14 days from CL/WJ and FP explants, respectively. The
      isolated cells were adherent to plastic and displayed fibroblastoid morphology
      and surface markers, such as CD29, CD44, CD73, CD90, and CD105, similarly to bone
      marrow (BM)-derived MSCs. However, the colony-forming efficiency of the cells
      varied, with CPJ-MSCs and WJ-MSCs showing higher efficiency than BM-MSCs. MSCs
      from all four sources differentiated into adipogenic, chondrogenic, and
      osteogenic lineages, indicating that they were multipotent. CPJ-MSCs
      differentiated more efficiently in comparison to other MSC sources. These results
      suggest that the CPJ is the most potent anatomical region and yields a higher
      number of cells, with greater proliferation and self-renewal capacities in vitro.
      In conclusion, the comparative analysis of the MSCs from the four sources
      indicated that CPJ is a more promising source of MSCs for cell therapy,
      regenerative medicine, and tissue engineering.

PMID- 28447992
TI  - Intravital Microscopy and Thrombus Induction in the Earlobe of a Hairless Mouse.
AB  - Thrombotic complications of vascular diseases are one leading cause of morbidity
      and mortality in industrial nations. Due to the complex interactions between
      cellular and non-cellular blood components during thrombus formation, reliable
      studies of the physiology and pathophysiology of thrombosis can only be performed
      in vivo. Therefore, this article presents an ear model in hairless mice and
      focuses on the in vivo analysis of microcirculation, thrombus formation, and
      thrombus evolution. By using intravital fluorescence microscopy and the
      intravenous (iv) application of the respective fluorescent dyes, a repetitive
      analysis of microcirculation in the auricle can easily be performed, without the
      need for surgical preparation. Furthermore, this model can be adapted for in vivo
      studies of different issues, including wound healing, reperfusion injury, or
      angiogenesis. In summary, the ear of hairless mice is an ideal model for the in
      vivo study of skin microcirculation in physiological or pathophysiological
      conditions and for the evaluation of its reaction to different systemic or
      topical treatments.

PMID- 28447993
TI  - Synthesis of 1,2-Azaborines and the Preparation of Their Protein Complexes with
      T4 Lysozyme Mutants.
AB  - We describe a general synthesis of 1,2-azaborines using standard air-free
      techniques and protein complex preparation with T4 lysozyme mutants by vapor
      diffusion. Oxygen- and moisture-sensitive compounds are prepared and isolated
      under an inert atmosphere (N2) using either a vacuum gas manifold or a glove box.
      As an example of azaborine synthesis, we demonstrate the synthesis and
      purification of the volatile N-H-B-ethyl-1,2-azaborine by a five-step sequence
      involving distillation and column chromatography for the isolation of products.
      T4 lysozyme mutants L99A and L99A/M102Q are expressed with Escherichia coli RR1
      strain. Standard protocols for chemical cell lysis followed by purification using
      carboxymethyl ion exchange column affords protein of sufficiently high purity for
      crystallization. Protein crystallization is performed in various concentrations
      of precipitant at different pH ranges using the hanging drop vapor diffusion
      method. Complex preparation with the small molecules is carried out by vapor
      diffusion method under an inert atmosphere. X-ray diffraction analysis of the
      crystal complex provides unambiguous structural evidence of binding interactions
      between the protein binding site and 1,2-azaborines.

PMID- 28447994
TI  - Scaling of Engineered Vascular Grafts Using 3D Printed Guides and the Ring
      Stacking Method.
AB  - Coronary artery disease remains a leading cause of death, affecting millions of
      Americans. With the lack of autologous vascular grafts available, engineered
      grafts offer great potential for patient treatment. However, engineered vascular
      grafts are generally not easily scalable, requiring manufacture of custom molds
      or polymer tubes in order to customize to different sizes, constituting a time
      consuming and costly practice. Human arteries range in lumen diameter from about
      2.0-38 mm and in wall thickness from about 0.5-2.5 mm. We have created a method,
      termed the "Ring Stacking Method," in which variable size rings of tissue of the
      desired cell type, demonstrated here with vascular smooth muscle cells (SMCs),
      can be created using guides of center posts to control lumen diameter and outer
      shells to dictate vessel wall thickness. These tissue rings are then stacked to
      create a tubular construct, mimicking the natural form of a blood vessel. The
      vessel length can be tailored by simply stacking the number of rings required to
      constitute the length needed. With our technique, tissues of tubular forms,
      similar to a blood vessel, can be readily manufactured in a variety of dimensions
      and lengths to meet the needs of the clinic and patient.

PMID- 28447995
TI  - Rapid and Refined CD11b Magnetic Isolation of Primary Microglia with Enhanced
      Purity and Versatility.
AB  - Microglia are the primary responders to central nervous system insults; however,
      much remains unknown about their role in regulating neuroinflammation. Microglia
      are mesodermal cells that function similarly to macrophages in surveying
      inflammatory stress. The classical (M1-type) and alternative (M2-type)
      activations of macrophages have also been extended to microglia in an effort to
      better understand the underlying interplay these phenotypes have in
      neuroinflammatory conditions such as Parkinson's, Alzheimer's, and Huntington's
      Diseases. In vitro experimentation utilizing primary microglia offers rapid and
      reliable results that may be extended to the in vivo environment. Although this
      is a clear advantage over in vivo experimentation, isolating microglia while
      achieving adequate yields of optimal purity has been a challenge. Common methods
      currently in use either suffer from low recovery, low purity, or both. Herein, we
      demonstrate a refinement of the column-free CD11b magnetic separation method that
      achieves a high cell recovery and enhanced purity in half the amount of time. We
      propose this optimized method as a highly useful model of primary microglial
      isolation for the purposes of studying neuroinflammation and neurodegeneration.

PMID- 28447996
TI  - Task Interruption and Resumption Paradigm for Testing the Activation and Pursuit
      of an Abstract Thinking Goal.
AB  - This protocol is based on the task interruption and resumption paradigm, the
      premise of which is that active goals lead to persistent behavior and thus a
      higher resumption rate after a period of delay or interruption. The task
      interruption and resumption protocol described in this research is tailored to
      test the activation of cognitive goals (e.g., a goal to think more abstractly).
      Cognitive goals may be pursued even during the interruption period; thus, to
      prevent this, the protocol involves cognitive distraction. The protocol consists
      of several stages. Specifically, the initial stage includes the goal activation
      process, where the treatment (versus control) condition receives a manipulation
      to activate the cognitive goal being tested by the researcher. In the next stage,
      participants are presented with the introduction of a task that is perceived to
      either satisfy or not satisfy the cognitive goal of interest. Importantly, this
      task is interrupted a few seconds after it begins. The task interruption forces a
      delay period and introduces a cognitive distraction to prevent the automatic
      pursuit and fulfillment of the cognitive goal. After the interruption period,
      participants are given a choice between resuming the interrupted task and
      abandoning the interrupted task to complete an alternative task instead. Among
      participants whose cognitive goals had been activated at the earlier stage, the
      task resumption rate should be higher if the task was perceived as an opportunity
      to satisfy (versus not satisfy) the goal. Such a finding would provide empirical
      evidence that the cognitive goal has been activated and pursued. In previous
      research, this protocol has been used to test whether causal uncertainty
      activates an abstract thinking goal. Adapting the protocol to test the activation
      of other cognitive goals is also discussed.

PMID- 28447997
TI  - Dielectric RheoSANS - Simultaneous Interrogation of Impedance, Rheology and Small
      Angle Neutron Scattering of Complex Fluids.
AB  - A procedure for the operation of a new dielectric RheoSANS instrument capable of
      simultaneous interrogation of the electrical, mechanical and microstructural
      properties of complex fluids is presented. The instrument consists of a Couette
      geometry contained within a modified forced convection oven mounted on a
      commercial rheometer. This instrument is available for use on the small angle
      neutron scattering (SANS) beamlines at the National Institute of Standards and
      Technology (NIST) Center for Neutron Research (NCNR). The Couette geometry is
      machined to be transparent to neutrons and provides for measurement of the
      electrical properties and microstructural properties of a sample confined between
      titanium cylinders while the sample undergoes arbitrary deformation.
      Synchronization of these measurements is enabled through the use of a
      customizable program that monitors and controls the execution of predetermined
      experimental protocols. Described here is a protocol to perform a flow sweep
      experiment where the shear rate is logarithmically stepped from a maximum value
      to a minimum value holding at each step for a specified period of time while
      frequency dependent dielectric measurements are made. Representative results are
      shown from a sample consisting of a gel composed of carbon black aggregates
      dispersed in propylene carbonate. As the gel undergoes steady shear, the carbon
      black network is mechanically deformed, which causes an initial decrease in
      conductivity associated with the breaking of bonds comprising the carbon black
      network. However, at higher shear rates, the conductivity recovers associated
      with the onset of shear thickening. Overall, these results demonstrate the
      utility of the simultaneous measurement of the rheo-electro-microstructural
      properties of these suspensions using the dielectric RheoSANS geometry.

PMID- 28447998
TI  - Characterization of Ultra-fine Grained and Nanocrystalline Materials Using
      Transmission Kikuchi Diffraction.
AB  - One of the challenges in microstructure analysis nowadays resides in the reliable
      and accurate characterization of ultra-fine grained (UFG) and nanocrystalline
      materials. The traditional techniques associated with scanning electron
      microscopy (SEM), such as electron backscatter diffraction (EBSD), do not possess
      the required spatial resolution due to the large interaction volume between the
      electrons from the beam and the atoms of the material. Transmission electron
      microscopy (TEM) has the required spatial resolution. However, due to a lack of
      automation in the analysis system, the rate of data acquisition is slow which
      limits the area of the specimen that can be characterized. This paper presents a
      new characterization technique, Transmission Kikuchi Diffraction (TKD), which
      enables the analysis of the microstructure of UFG and nanocrystalline materials
      using an SEM equipped with a standard EBSD system. The spatial resolution of this
      technique can reach 2 nm. This technique can be applied to a large range of
      materials that would be difficult to analyze using traditional EBSD. After
      presenting the experimental set up and describing the different steps necessary
      to realize a TKD analysis, examples of its use on metal alloys and minerals are
      shown to illustrate the resolution of the technique and its flexibility in term
      of material to be characterized.

PMID- 28447999
TI  - Exposure of the Pig CNS for Histological Analysis: A Manual for Decapitation,
      Skull Opening, and Brain Removal.
AB  - Pigs have become increasingly popular in large-animal translational neuroscience
      research as an economically and ethically feasible substitute to non-human
      primates. The large brain size of the pig allows the use of conventional clinical
      brain imagers and the direct use and testing of neurosurgical procedures and
      equipment from the human clinic. Further macroscopic and histological analysis,
      however, requires postmortem exposure of the pig central nervous system (CNS) and
      subsequent brain removal. This is not an easy task, as the pig CNS is
      encapsulated by a thick, bony skull and spinal column. The goal of this paper and
      instructional video is to describe how to expose and remove the postmortem pig
      brain and the pituitary gland in an intact state, suitable for subsequent
      macroscopic and histological analysis.

PMID- 28448000
TI  - High-resolution Imaging and Analysis of Individual Astral Microtubule Dynamics in
      Budding Yeast.
AB  - Dynamic microtubules are fundamental to many cellular processes, and accurate
      measurements of microtubule dynamics can provide insight into how cells regulate
      these processes and how genetic mutations impact regulation. The quantification
      of microtubule dynamics in metazoan models has a number of associated challenges,
      including a high microtubule density and limitations on genetic manipulations. In
      contrast, the budding yeast model offers advantages that overcome these
      challenges. This protocol describes a method to measure the dynamics of single
      microtubules in living yeast cells. Cells expressing fluorescently tagged tubulin
      are adhered to assembled slide chambers, allowing for stable time-lapse image
      acquisition. A detailed guide for high-speed, four-dimensional image acquisition
      is also provided, as well as a protocol for quantifying the properties of dynamic
      microtubules in confocal image stacks. This method, combined with conventional
      yeast genetics, provides an approach that is uniquely suited for quantitatively
      assessing the effects of microtubule regulators or mutations that alter the
      activity of tubulin subunits.

PMID- 28448001
TI  - Repeated Measurement of Respiratory Muscle Activity and Ventilation in Mouse
      Models of Neuromuscular Disease.
AB  - Accessory respiratory muscles help to maintain ventilation when diaphragm
      function is impaired. The following protocol describes a method for repeated
      measurements over weeks or months of accessory respiratory muscle activity while
      simultaneously measuring ventilation in a non-anesthetized, freely behaving
      mouse. The technique includes the surgical implantation of a radio transmitter
      and the insertion of electrode leads into the scalene and trapezius muscles to
      measure the electromyogram activity of these inspiratory muscles. Ventilation is
      measured by whole-body plethysmography, and animal movement is assessed by video
      and is synchronized with electromyogram activity. Measurements of muscle activity
      and ventilation in a mouse model of amyotrophic lateral sclerosis are presented
      to show how this tool can be used to investigate how respiratory muscle activity
      changes over time and to assess the impact of muscle activity on ventilation. The
      described methods can easily be adapted to measure the activity of other muscles
      or to assess accessory respiratory muscle activity in additional mouse models of
      disease or injury.

PMID- 28448003
TI  - Standardized Method for Measuring Collection Efficiency from Wipe-sampling of
      Trace Explosives.
AB  - One of the limiting steps to detecting traces of explosives at screening venues
      is effective collection of the sample. Wipe-sampling is the most common procedure
      for collecting traces of explosives, and standardized measurements of collection
      efficiency are needed to evaluate and optimize sampling protocols. The approach
      described here is designed to provide this measurement infrastructure, and
      controls most of the factors known to be relevant to wipe-sampling. Three
      critical factors (the applied force, travel distance, and travel speed) are
      controlled using an automated device. Test surfaces are chosen based on
      similarity to the screening environment, and the wipes can be made from any
      material considered for use in wipe-sampling. Particle samples of the explosive
      1,3,5-trinitroperhydro-1,3,5-triazine (RDX) are applied in a fixed location on
      the surface using a dry-transfer technique. The particle samples, recently
      developed to simulate residues made after handling explosives, are produced by
      inkjet printing of RDX solutions onto polytetrafluoroethylene (PTFE) substrates.
      Collection efficiency is measured by extracting collected explosive from the
      wipe, and then related to critical sampling factors and the selection of wipe
      material and test surface. These measurements are meant to guide the development
      of sampling protocols at screening venues, where speed and throughput are primary
      considerations.

PMID- 28448004
TI  - Live Confocal Imaging of Developing Arabidopsis Flowers.
AB  - The study of plant growth and development has long relied on experimental
      techniques using dead, fixed tissues and lacking proper cellular resolution.
      Recent advances in confocal microscopy, combined with the development of numerous
      fluorophores, have overcome these issues and opened the possibility to study the
      expression of several genes simultaneously, with a good cellular resolution, in
      live samples. Live confocal imaging provides plant biologists with a powerful
      tool to study development, and has been extensively used to study root growth and
      the formation of lateral organs on the flanks of the shoot apical meristem.
      However, it has not been widely applied to the study of flower development, in
      part due to challenges that are specific to imaging flowers, such as the sepals
      that grow over the flower meristem, and filter out the fluorescence from
      underlying tissues. Here, we present a detailed protocol to perform live confocal
      imaging on live, developing Arabidopsis flower buds, using either an upright or
      an inverted microscope.

PMID- 28448002
TI  - Measurement of T Cell Alloreactivity Using Imaging Flow Cytometry.
AB  - The measurement of immunological reactivity to donor antigens in transplant
      recipients is likely to be crucial for the successful reduction or withdrawal of
      immunosuppression. The mixed leukocyte reaction (MLR), limiting dilution assays,
      and trans-vivo delayed-type hypersensitivity (DTH) assay have all been applied to
      this question, but these methods have limited predictive ability and/or
      significant practical limitations that reduce their usefulness. Imaging flow
      cytometry is a technique that combines the multiparametric quantitative powers of
      flow cytometry with the imaging capabilities of fluorescent microscopy. We
      recently made use of an imaging flow cytometry approach to define the proportion
      of recipient T cells capable of forming mature immune synapses with donor antigen
      presenting cells (APCs). Using a well-characterized mouse heart transplant model,
      we have shown that the frequency of in vitro immune synapses among T-APC membrane
      contact events strongly predicted allograft outcome in rejection, tolerance, and
      a situation where transplant survival depends on induced regulatory T cells. The
      frequency of T-APC contacts increased with T cells from mice during acute
      rejection and decreased with T cells from mice rendered unresponsive to
      alloantigen. The addition of regulatory T cells to the in vitro system reduced
      prolonged T-APC contacts. Critically, this effect was also seen with human
      polyclonally expanded, naturally occurring regulatory T cells, which are known to
      control the rejection of human tissues in humanized mouse models. Further
      development of this approach may allow for a deeper characterization of the
      alloreactive T-cell compartment in transplant recipients. In the future, further
      development and evaluation of this method using human cells may form the basis
      for assays used to select patients for immunosuppression minimization, and it can
      be used to measure the impact of tolerogenic therapies in the clinic.

PMID- 28448005
TI  - Open-source Single-particle Analysis for Super-resolution Microscopy with
      VirusMapper.
AB  - Super-resolution fluorescence microscopy is currently revolutionizing cell
      biology research. Its capacity to break the resolution limit of around 300 nm
      allows for the routine imaging of nanoscale biological complexes and processes.
      This increase in resolution also means that methods popular in electron
      microscopy, such as single-particle analysis, can readily be applied to super
      resolution fluorescence microscopy. By combining this analytical approach with
      super-resolution optical imaging, it becomes possible to take advantage of the
      molecule-specific labeling capacity of fluorescence microscopy to generate
      structural maps of molecular elements within a metastable structure. To this end,
      we have developed a novel algorithm - VirusMapper - packaged as an easy-to-use,
      high-performance, and high-throughput ImageJ plugin. This article presents an in
      depth guide to this software, showcasing its ability to uncover novel structural
      features in biological molecular complexes. Here, we present how to assemble
      compatible data and provide a step-by-step protocol on how to use this algorithm
      to apply single-particle analysis to super-resolution images.

PMID- 28448006
TI  - Purification of High Molecular Weight Genomic DNA from Powdery Mildew for Long
      Read Sequencing.
AB  - The powdery mildew fungi are a group of economically important fungal plant
      pathogens. Relatively little is known about the molecular biology and genetics of
      these pathogens, in part due to a lack of well-developed genetic and genomic
      resources. These organisms have large, repetitive genomes, which have made genome
      sequencing and assembly prohibitively difficult. Here, we describe methods for
      the collection, extraction, purification and quality control assessment of high
      molecular weight genomic DNA from one powdery mildew species, Golovinomyces
      cichoracearum. The protocol described includes mechanical disruption of spores
      followed by an optimized phenol/chloroform genomic DNA extraction. A typical
      yield was 7 ug DNA per 150 mg conidia. The genomic DNA that is isolated using
      this procedure is suitable for long-read sequencing (i.e., > 48.5 kbp). Quality
      control measures to ensure the size, yield, and purity of the genomic DNA are
      also described in this method. Sequencing of the genomic DNA of the quality
      described here will allow for the assembly and comparison of multiple powdery
      mildew genomes, which in turn will lead to a better understanding and improved
      control of this agricultural pathogen.

PMID- 28448007
TI  - A Novel Biaxial Testing Apparatus for the Determination of Forming Limit under
      Hot Stamping Conditions.
AB  - The hot stamping and cold die quenching process is increasingly used to form
      complex shaped structural components of sheet metals. Conventional experimental
      approaches, such as out-of-plane and in-plane tests, are not applicable to the
      determination of forming limits when heating and rapid cooling processes are
      introduced prior to forming for tests conducted under hot stamping conditions. A
      novel in-plane biaxial testing system was designed and used for the determination
      of forming limits of sheet metals at various strain paths, temperatures, and
      strain rates after heating and cooling processes in a resistance heating uniaxial
      testing machine. The core part of the biaxial testing system is a biaxial
      apparatus, which transfers a uniaxial force provided by the uniaxial testing
      machine to a biaxial force. One type of cruciform specimen was designed and
      verified for the formability test of aluminum alloy 6082 using the proposed
      biaxial testing system. The digital image correlation (DIC) system with a high
      speed camera was used for taking strain measurements of a specimen during a
      deformation. The aim of proposing this biaxial testing system is to enable the
      forming limits of an alloy to be determined at various temperatures and strain
      rates under hot stamping conditions.

PMID- 28448008
TI  - A Protocol for Using Forster Resonance Energy Transfer (FRET)-force Biosensors to
      Measure Mechanical Forces across the Nuclear LINC Complex.
AB  - The LINC complex has been hypothesized to be the critical structure that mediates
      the transfer of mechanical forces from the cytoskeleton to the nucleus. Nesprin
      2G is a key component of the LINC complex that connects the actin cytoskeleton to
      membrane proteins (SUN domain proteins) in the perinuclear space. These membrane
      proteins connect to lamins inside the nucleus. Recently, a Forster Resonance
      Energy Transfer (FRET)-force probe was cloned into mini-Nesprin-2G (Nesprin-TS
      (tension sensor)) and used to measure tension across Nesprin-2G in live NIH3T3
      fibroblasts. This paper describes the process of using Nesprin-TS to measure LINC
      complex forces in NIH3T3 fibroblasts. To extract FRET information from Nesprin
      TS, an outline of how to spectrally unmix raw spectral images into acceptor and
      donor fluorescent channels is also presented. Using open-source software
      (ImageJ), images are pre-processed and transformed into ratiometric images.
      Finally, FRET data of Nesprin-TS is presented, along with strategies for how to
      compare data across different experimental groups.

PMID- 28448009
TI  - Using Primary Neurosphere Cultures to Study Primary Cilia.
AB  - The primary cilium is fundamentally important for the proliferation of neural
      stem/progenitor cells and for neuronal differentiation during embryonic,
      postnatal, and adult life. In addition, most differentiated neurons possess
      primary cilia that house signaling receptors, such as G-protein-coupled
      receptors, and signaling molecules, such as adenylyl cyclases. The primary cilium
      determines the activity of multiple developmental pathways, including the sonic
      hedgehog pathway during embryonic neuronal development, and also functions in
      promoting compartmentalized subcellular signaling during adult neuronal function.
      Unsurprisingly, defects in primary cilium biogenesis and function have been
      linked to developmental anomalies of the brain, central obesity, and learning and
      memory deficits. Thus, it is imperative to study primary cilium biogenesis and
      ciliary trafficking in the context of neural stem/progenitor cells and
      differentiated neurons. However, culturing methods for primary neurons require
      considerable expertise and are not amenable to freeze-thaw cycles. In this
      protocol, we discuss culturing methods for mixed populations of neural
      stem/progenitor cells using primary neurospheres. The neurosphere-based culturing
      methods provide the combined benefits of studying primary neural stem/progenitor
      cells: amenability to multiple passages and freeze-thaw cycles, differentiation
      potential into neurons/glia, and transfectability. Importantly, we determined
      that neurosphere-derived neural stem/progenitor cells and differentiated neurons
      are ciliated in culture and localize signaling molecules relevant to ciliary
      function in these compartments. Utilizing these cultures, we further describe
      methods to study ciliogenesis and ciliary trafficking in neural stem/progenitor
      cells and differentiated neurons. These neurosphere-based methods allow us to
      study cilia-regulated cellular pathways, including G-protein-coupled receptor and
      sonic hedgehog signaling, in the context of neural stem/progenitor cells and
      differentiated neurons.

PMID- 28448010
TI  - Murine Left Anterior Descending (LAD) Coronary Artery Ligation: An Improved and
      Simplified Model for Myocardial Infarction.
AB  - Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the
      leading causes of death in the United States. IHD is characterized by reduced
      blood supply to the heart, resulting in the loss of oxygen to and the ensuing
      necrosis of the heart muscle. The MI model has gained popularity for its use as a
      short-term ischemia-reperfusion model and a long-term permanent ligation model.
      Below, we describe a reliable method for the permanent ligation of the LAD. With
      mouse genetic engineering technology becoming more advanced, and with an
      increasing availability of quality murine surgical instruments, the mouse has
      become a popular model for MI surgeries. Our surgical model incorporates the use
      of an easily reversible anesthetic for the rapid recovery of the mouse; a
      minimally invasive endotracheal intubation without involving a tracheotomy; and a
      thoracentesis through the original thoracotomy site without creating an
      additional incision in the chest, as is done in some other methods, to
      effectively remove excess blood and air from the chest cavity. This method is
      comparatively less invasive than other methods, which dramatically reduces
      surgical and post-surgical complications and mortality and improves
      reproducibility.

PMID- 28448011
TI  - Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor
      Brilliant Blue FCF on Collagen-induced Aggregation.
AB  - Turbidimetry is a laboratory technique that is applied to measure the aggregation
      of platelets suspended in either plasma (platelet-rich plasma, PRP) or in buffer
      (washed platelets), by the use of one or a combination of agonists. The use of
      washed platelets separated from their plasma environment and in the absence of
      anticoagulants allows for studying intrinsic platelet properties. Among the large
      panel of agonists, arachidonic acid (AA), adenosine di-phosphate (ADP), thrombin
      and collagen are the most frequently used. The aggregation response is quantified
      by measuring the relative optical density (OD) over time of platelet suspension
      under continuous stirring. Platelets in homogeneous suspension limit the passage
      of light after the addition of an agonist, platelet shape change occurs producing
      a small transitory increase in OD. Following this initial activation step,
      platelet clots form gradually, allowing the passage of light through the
      suspension as a result of decreased OD. The aggregation process is ultimately
      expressed as a percentage, compared to the OD of platelet-poor plasma or buffer.
      Rigorous calibration is thus essential at the beginning of each experiment. As a
      general rule: calibration to 0% is set by measuring the OD of a non-stimulated
      platelet suspension while measuring the OD of the suspension medium containing no
      platelets represents a value of 100%. Platelet aggregation is generally
      visualized as a real-time aggregation curve. Turbidimetry is one of the most
      commonly used laboratory techniques for the investigation of platelet function
      and is considered as the historical gold standard and used for the development of
      new pharmaceutical agents aimed at inhibiting platelet aggregation. Here, we
      describe detailed protocols for 1) preparation of human washed platelets and 2)
      turbidimetric analysis of collagen-induced aggregation of human washed platelets
      pretreated with the food dye Brilliant Blue FCF that was recently identified as
      an inhibitor of Pannexin1 (Panx1) channels.

PMID- 28448012
TI  - Protocols for Visualizing Steroidogenic Organs and Their Interactive Organs with
      Immunostaining in the Fruit Fly Drosophila melanogaster.
AB  - In multicellular organisms, a small group of cells is endowed with a specialized
      function in their biogenic activity, inducing a systemic response to growth and
      reproduction. In insects, the larval prothoracic gland (PG) and the adult female
      ovary play essential roles in biosynthesizing the principal steroid hormones
      called ecdysteroids. These ecdysteroidogenic organs are innervated from the
      nervous system, through which the timing of biosynthesis is affected by
      environmental cues. Here we describe a protocol for visualizing ecdysteroidogenic
      organs and their interactive organs in larvae and adults of the fruit fly
      Drosophila melanogaster, which provides a suitable model system for studying
      steroid hormone biosynthesis and its regulatory mechanism. Skillful dissection
      allows us to maintain the positions of ecdysteroidogenic organs and their
      interactive organs including the brain, the ventral nerve cord, and other
      tissues. Immunostaining with antibodies against ecdysteroidogenic enzymes, along
      with transgenic fluorescence proteins driven by tissue-specific promoters, are
      available to label ecdysteroidogenic cells. Moreover, the innervations of the
      ecdysteroidogenic organs can also be labeled by specific antibodies or a
      collection of GAL4 drivers in various types of neurons. Therefore, the
      ecdysteroidogenic organs and their neuronal connections can be visualized
      simultaneously by immunostaining and transgenic techniques. Finally, we describe
      how to visualize germline stem cells, whose proliferation and maintenance are
      controlled by ecdysteroids. This method contributes to comprehensive
      understanding of steroid hormone biosynthesis and its neuronal regulatory
      mechanism.

PMID- 28448013
TI  - Precision-cut Mouse Lung Slices to Visualize Live Pulmonary Dendritic Cells.
AB  - Inhalation of allergens and pathogens elicits multiple changes in a variety of
      immune cell types in the lung. Flow cytometry is a powerful technique for
      quantitative analysis of cell surface proteins on immune cells, but it provides
      no information on the localization and migration patterns of these cells within
      the lung. Similarly, chemotaxis assays can be performed to study the potential of
      cells to respond to chemotactic factors in vitro, but these assays do not
      reproduce the complex environment of the intact lung. In contrast to these
      aforementioned techniques, the location of individual cell types within the lung
      can be readily visualized by generating Precision-cut Lung Slices (PCLS),
      staining them with commercially available, fluorescently tagged antibodies, and
      visualizing the sections by confocal microscopy. PCLS can be used for both live
      and fixed lung tissue, and the slices can encompass areas as large as a cross
      section of an entire lobe. We have used this protocol to successfully visualize
      the location of a wide variety of cell types in the lung, including distinct
      types of dendritic cells, macrophages, neutrophils, T cells and B cells, as well
      as structural cells such as lymphatic, endothelial, and epithelial cells. The
      ability to visualize cellular interactions, such as those between dendritic cells
      and T cells, in live, three-dimensional lung tissue, can reveal how cells move
      within the lung and interact with one another at steady state and during
      inflammation. Thus, when used in combination with other procedures, such as flow
      cytometry and quantitative PCR, PCLS can contribute to a comprehensive
      understanding of cellular events that underlie allergic and inflammatory diseases
      of the lung.

PMID- 28448014
TI  - An Efficient and Flexible Cell Aggregation Method for 3D Spheroid Production.
AB  - Monolayer cell culture does not adequately model the in vivo behavior of tissues,
      which involves complex cell-cell and cell-matrix interactions. Three-dimensional
      (3D) cell culture techniques are a recent innovation developed to address the
      shortcomings of adherent cell culture. While several techniques for generating
      tissue analogues in vitro have been developed, these methods are frequently
      complex, expensive to establish, require specialized equipment, and are generally
      limited by compatibility with only certain cell types. Here, we describe a rapid
      and flexible protocol for aggregating cells into multicellular 3D spheroids of
      consistent size that is compatible with growth of a variety of tumor and normal
      cell lines. We utilize varying concentrations of serum and methyl cellulose (MC)
      to promote anchorage-independent spheroid generation and prevent the formation of
      cell monolayers in a highly reproducible manner. Optimal conditions for
      individual cell lines can be achieved by adjusting MC or serum concentrations in
      the spheroid formation medium. The 3D spheroids generated can be collected for
      use in a wide range of applications, including cell signaling or gene expression
      studies, candidate drug screening, or in the study of cellular processes such as
      tumor cell invasion and migration. The protocol is also readily adapted to
      generate clonal spheroids from single cells, and can be adapted to assess
      anchorage-independent growth and anoikis-resistance. Overall, our protocol
      provides an easily modifiable method for generating and utilizing 3D cell
      spheroids in order to recapitulate the 3D microenvironment of tissues and model
      the in vivo growth of normal and tumor cells.

PMID- 28448015
TI  - Quantification of Strain in a Porcine Model of Skin Expansion Using Multi-View
      Stereo and Isogeometric Kinematics.
AB  - Tissue expansion is a popular technique in plastic and reconstructive surgery
      that grows skin in vivo for correction of large defects such as burns and giant
      congenital nevi. Despite its widespread use, planning and executing an expansion
      protocol is challenging due to the difficulty in measuring the deformation
      imposed at each inflation step and over the length of the procedure. Quantifying
      the deformation fields is crucial, as the distribution of stretch over time
      determines the rate and amount of skin grown at the end of the treatment. In this
      manuscript, we present a method to study tissue expansion in order to gain
      quantitative knowledge of the deformations induced during an expansion process.
      This experimental protocol incorporates multi-view stereo and isogeometric
      kinematic analysis in a porcine model of tissue expansion. Multi-view stereo
      allows three-dimensional geometric reconstruction from uncalibrated sequences of
      images. The isogeometric kinematic analysis uses splines to describe the regional
      deformations between smooth surfaces with few mesh points. Our protocol has the
      potential to bridge the gap between basic scientific inquiry regarding the
      mechanics of skin expansion and the clinical setting. Eventually, we expect that
      the knowledge gained with our methodology will enable treatment planning using
      computational simulations of skin deformation in a personalized manner.

PMID- 28448016
TI  - Zebrafish In Situ Spinal Cord Preparation for Electrophysiological Recordings
      from Spinal Sensory and Motor Neurons.
AB  - Zebrafish, first introduced as a developmental model, have gained popularity in
      many other fields. The ease of rearing large numbers of rapidly developing
      organisms, combined with the embryonic optical clarity, served as initial
      compelling attributes of this model. Over the past two decades, the success of
      this model has been further propelled by its amenability to large-scale
      mutagenesis screens and by the ease of transgenesis. More recently, gene-editing
      approaches have extended the power of the model. For neurodevelopmental studies,
      the zebrafish embryo and larva provide a model to which multiple methods can be
      applied. Here, we focus on methods that allow the study of an essential property
      of neurons, electrical excitability. Our preparation for the electrophysiological
      study of zebrafish spinal neurons involves the use of veterinarian suture glue to
      secure the preparation to a recording chamber. Alternative methods for recording
      from zebrafish embryos and larvae involve the attachment of the preparation to
      the chamber using a fine tungsten pin1,2,3,4,5. A tungsten pin is most often used
      to mount the preparation in a lateral orientation, although it has been used to
      mount larvae dorsal-side up4. The suture glue has been used to mount embryos and
      larvae in both orientations. Using the glue, a minimal dissection can be
      performed, allowing access to spinal neurons without the use of an enzymatic
      treatment, thereby avoiding any resultant damage. However, for larvae, it is
      necessary to apply a brief enzyme treatment to remove the muscle tissue
      surrounding the spinal cord. The methods described here have been used to study
      the intrinsic electrical properties of motor neurons, interneurons, and sensory
      neurons at several developmental stages6,7,8,9.

PMID- 28448017
TI  - Low-Density Primary Hippocampal Neuron Culture.
AB  - The ability to probe the structure and physiology of individual nerve cells in
      culture is crucial to the study of neurobiology, and allows for flexibility in
      genetic and chemical manipulation of individual cells or defined networks. Such
      ease of manipulation is simpler in the reduced culture system when compared to
      the intact brain tissue. While many methods for the isolation and growth of these
      primary neurons exist, each has its own limitations. This protocol describes a
      method for culturing low-density and high-purity rodent embryonic hippocampal
      neurons on glass coverslips, which are then suspended over a monolayer of glial
      cells. This 'sandwich culture' allows for exclusive long-term growth of a
      population of neurons while allowing for trophic support from the underlying
      glial monolayer. When neurons are of sufficient age or maturity level, the neuron
      coverslips can be flipped-out of the glial dish and used in imaging or functional
      assays. Neurons grown by this method typically survive for several weeks and
      develop extensive arbors, synaptic connections, and network properties.

PMID- 28448018
TI  - Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in
      Response to A. fumigatus.
AB  - Aspergillus fumigatus is an opportunistic fungal pathogen causing invasive
      infections in immunocompromised hosts with a high case-fatality rate. Research
      investigating immunological responses against A. fumigatus has been limited by
      the lack of consistent and reliable assays for measuring the antifungal activity
      of specific immune cells in vitro. A new method is described to assess the
      antifungal activity of primary monocytes and neutrophils from human donors
      against A. fumigatus using FLuorescent Aspergillus REporter (FLARE) conidia.
      These conidia contain a genetically encoded dsRed reporter, which is
      constitutively expressed by live FLARE conidia, and are externally labeled with
      Alexa Fluor 633, which is resistant to degradation within the phagolysosome, thus
      allowing a distinction between live and dead A. fumigatus conidia. Video
      microscopy and flow cytometry are subsequently used to visualize the interaction
      between conidia and innate immune cells, assessing fungicidal activity whilst
      also providing a wealth of information on phagocyte migration, phagocytosis and
      the inhibition of fungal growth. This novel technique has already provided
      exciting new insights into the host-pathogen interaction of primary immune cells
      against A. fumigatus. It is important to note the laboratory setup required to
      perform this assay, including the necessary microscopy and flow cytometry
      facilities, and the capacity to work with human donor blood and genetically
      manipulated fungi. However, this assay is capable of generating large amounts of
      data and can reveal detailed insights into the antifungal response. This protocol
      has successfully been used to study the host-pathogen interaction of primary
      immune cells against A. fumigatus. It is important to note the laboratory setup
      required to perform this assay, including the necessary microscopy and flow
      cytometry facilities, and the capacity to work with human donor blood and
      genetically manipulated fungi. However, this assay is capable of generating large
      amounts of data and can reveal detailed insights into the antifungal response.
      This protocol has successfully been used to study the host-pathogen interaction
      of primary immune cells against A. fumigatus.

PMID- 28448019
TI  - A Tandem Liquid Chromatography-Mass Spectrometry-based Approach for Metabolite
      Analysis of Staphylococcus aureus.
AB  - In an effort to thwart bacterial pathogens, hosts often limit the availability of
      nutrients at the site of infection. This limitation can alter the abundances of
      key metabolites to which regulatory factors respond, adjusting cellular
      metabolism. In recent years, a number of proteins and RNA have emerged as
      important regulators of virulence gene expression. For example, the CodY protein
      responds to levels of branched-chain amino acids and GTP and is widely conserved
      in low G+C Gram-positive bacteria. As a global regulator in Staphylococcus
      aureus, CodY controls the expression of dozens of virulence and metabolic genes.
      We hypothesize that S. aureus uses CodY, in part, to alter its metabolic state in
      an effort to adapt to nutrient-limiting conditions potentially encountered in the
      host environment. This manuscript describes a method for extracting and analyzing
      metabolites from S. aureus using liquid chromatography coupled with mass
      spectrometry, a protocol that was developed to test this hypothesis. The method
      also highlights best practices that will ensure rigor and reproducibility, such
      as maintaining biological steady state and constant aeration without the use of
      continuous chemostat cultures. Relative to the USA200 methicillin-susceptible S.
      aureus isolate UAMS-1 parental strain, the isogenic codY mutant exhibited
      significant increases in amino acids derived from aspartate (e.g., threonine and
      isoleucine) and decreases in their precursors (e.g., aspartate and O
      acetylhomoserine). These findings correlate well with transcriptional data
      obtained with RNA-seq analysis: genes in these pathways were up-regulated between
      10- and 800-fold in the codY null mutant. Coupling global analyses of the
      transcriptome and the metabolome can reveal how bacteria alter their metabolism
      when faced with environmental or nutritional stress, providing potential insight
      into the physiological changes associated with nutrient depletion experienced
      during infection. Such discoveries may pave the way for the development of novel
      anti-infectives and therapeutics.

PMID- 28448020
TI  - Analysis of Lymphocyte Extravasation Using an In Vitro Model of the Human Blood
      brain Barrier.
AB  - Lymphocyte extravasation into the central nervous system (CNS) is critical for
      immune surveillance. Disease-related alterations of lymphocyte extravasation
      might result in pathophysiological changes in the CNS. Thus, investigation of
      lymphocyte migration into the CNS is important to understand inflammatory CNS
      diseases and to develop new therapy approaches. Here we present an in vitro model
      of the human blood-brain barrier to study lymphocyte extravasation. Human brain
      microvascular endothelial cells (HBMEC) are confluently grown on a porous
      polyethylene terephthalate transwell insert to mimic the endothelium of the blood
      brain barrier. Barrier function is validated by zonula occludens
      immunohistochemistry, transendothelial electrical resistance (TEER) measurements
      as well as analysis of evans blue permeation. This model allows investigation of
      the diapedesis of rare lymphocyte subsets such as CD56brightCD16dim/- NK cells.
      Furthermore, the effects of other cells, cytokines and chemokines, disease
      related alterations, and distinct treatment regimens on the migratory capacity of
      lymphocytes can be studied. Finally, the impact of inflammatory stimuli as well
      as different treatment regimens on the endothelial barrier can be analyzed.

PMID- 28448021
TI  - Detection of Ligand-activated G Protein-coupled Receptor Internalization by
      Confocal Microscopy.
AB  - Confocal laser scanning microscopy (CLSM) is an optical imaging technique for
      high-contrast imaging. It is a powerful approach to visualize fluorescent fusion
      proteins, such as green fluorescent protein (GFP), to determine their expression,
      localization, and function. The subcellular localization of target proteins is
      important for identification, characterization, and functional analyses.
      Internalization is one of the predominant mechanisms controlling G protein
      coupled receptor (GPCR) signaling to ensure the appropriate cellular responses to
      stimuli. Here, we describe an experimental method to detect the subcellular
      localization and internalization of GPCR in HEK293 cells with confocal
      microscopy. In addition, this experiment provides some details about cell culture
      and transfection. This protocol is compatible with a variety of widely available
      fluorescent markers and is applicable to the visualization of the subcellular
      localization of a majority of proteins, as well as of the internalization of
      GPCR. This technique should enable researchers to efficiently manipulate GPCR
      gene expression in mammalian cell lines and should facilitate studies on GPCR
      subcellular localization and internalization.

PMID- 28448022
TI  - Development of an Economical DNA Delivery System by "Acufection" and its
      Application to Skin Research.
AB  - Dysregulation of immune response in skin is associated with numerous human skin
      disorders. Direct transfer of immune-related genes into skin tissue is a
      fascinating approach to investigate immune modulation of cutaneous inflammation
      in mouse models of human diseases. Here we present a cost-effective protocol that
      delivered naked DNA in mouse skin and leads to transgene expression. The method
      is coined "acufection", denoting acupuncture-mediated DNA transfection. To
      perform acufection, mouse skin was first infused with DNA in phosphate-buffered
      saline (PBS) and then pricked lightly with a bundle of acupuncture needles to
      facilitate the absorption of DNA and transfection into cells. The plasmid DNA is
      presumably taken up by the keratinocyte and dendritic cells (DCs) in the skin and
      expressed into protein. Mechanical prick with the needles per se did not cause
      skin damage or induce keratinocyte activation. The expression of the transfected
      genes was detected in the skin at both transcriptional and translational levels
      following acufection for 2 days and maintained up to 7 days. The primary goal for
      the development of this acufection method was to investigate a previously
      undefined isoform of IL-15. Using this method, an alternatively spliced IL-15
      isoform with partially deleted exon 7 (IL-15DeltaE7) was expressed in the skin
      and subsequently treated with a Toll-like receptor 7 (TLR7) agonist, imiquimod
      (IMQ), to induce inflammation. Acufection-delivered IL-15DeltaE7 in skin
      suppressed keratinocyte proliferation, epidermal thickness and neutrophil
      recruitment in IMQ-induced cutaneous inflammation. With increasing interest in
      identifying the regulatory mechanisms of cutaneous inflammation, the protocol
      described here provides a cost effective and versatile alternative to the gene
      gun system or microseeding for DNA delivery in vivo. It may potentially allow
      discovery of the function of a novel gene in the skin or for investigating new
      treatment for cutaneous diseases.

PMID- 28448023
TI  - Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells.
AB  - Phenotypic plasticity refers to a phenomenon in which cells transiently gain
      traits of another lineage. During carcinoma progression, phenotypic plasticity
      drives invasion, dissemination and metastasis. Indeed, while most of the studies
      of phenotypic plasticity have been in the context of epithelial-derived
      carcinomas, it turns out sarcomas, which are mesenchymal in origin, also exhibit
      phenotypic plasticity, with a subset of sarcomas undergoing a phenomenon that
      resembles a mesenchymal-epithelial transition (MET). Here, we developed a method
      comprising the miR-200 family and grainyhead-like 2 (GRHL2) to mimic this MET
      like phenomenon observed in sarcoma patient samples.We sequentially express GRHL2
      and the miR-200 family using cell transduction and transfection, respectively, to
      better understand the molecular underpinnings of these phenotypic transitions in
      sarcoma cells. Sarcoma cells expressing miR-200s and GRHL2 demonstrated enhanced
      epithelial characteristics in cell morphology and alteration of epithelial and
      mesenchymal biomarkers. Future studies using these methods can be used to better
      understand the phenotypic consequences of MET-like processes on sarcoma cells,
      such as migration, invasion, metastatic propensity, and therapy resistance.

PMID- 28448024
TI  - Synthesis of Hydrogels with Antifouling Properties As Membranes for Water
      Purification.
AB  - Hydrogels have been widely utilized to enhance the surface hydrophilicity of
      membranes for water purification, increasing the antifouling properties and thus
      achieving stable water permeability through membranes over time. Here, we report
      a facile method to prepare hydrogels based on zwitterions for membrane
      applications. Freestanding films can be prepared from sulfobetaine methacrylate
      (SBMA) with a crosslinker of poly(ethylene glycol) diacrylate (PEGDA) via
      photopolymerization. The hydrogels can also be prepared by impregnation into
      hydrophobic porous supports to enhance the mechanical strength. These films can
      be characterized by attenuated total reflection Fourier transform infrared
      spectroscopy (ATR-FTIR) to determine the degree of conversion of the
      (meth)acrylate groups, using goniometers for hydrophilicity and differential
      scanning calorimetry (DSC) for polymer chain dynamics. We also report protocols
      to determine the water permeability in dead-end filtration systems and the effect
      of foulants (bovine serum albumin, BSA) on membrane performance.

PMID- 28448025
TI  - Novel Assay for Cold Nociception in Drosophila Larvae.
AB  - How organisms sense and respond to noxious temperatures is still poorly
      understood. Further, the mechanisms underlying sensitization of the sensory
      machinery, such as in patients experiencing peripheral neuropathy or injury
      induced sensitization, are not well characterized. The genetically tractable
      Drosophila model has been used to study the cells and genes required for noxious
      heat detection, which has yielded multiple conserved genes of interest. Little is
      known however about the cells and receptors important for noxious cold sensing.
      Although, Drosophila does not survive prolonged exposure to cold temperatures
      (<=10 oC), and will avoid cool, preferring warmer temperatures in behavioral
      preference assays, how they sense and possibly avoid noxious cold stimuli has
      only recently been investigated. Here we describe and characterize the first
      noxious cold (<=10 oC) behavioral assay in Drosophila. Using this tool and assay,
      we show an investigator how to qualitatively and quantitatively assess cold
      nociceptive behaviors. This can be done under normal/healthy culture conditions,
      or presumably in the context of disease, injury or sensitization. Further, this
      assay can be applied to larvae selected for desired genotypes, which might impact
      thermosensation, pain, or nociceptive sensitization. Given that pain is a highly
      conserved process, using this assay to further study thermal nociception will
      likely glean important understanding of pain processes in other species,
      including vertebrates.

PMID- 28448026
TI  - LERLIC-MS/MS for In-depth Characterization and Quantification of Glutamine and
      Asparagine Deamidation in Shotgun Proteomics.
AB  - Characterization of protein deamidation is imperative to decipher the role(s) and
      potentialities of this protein posttranslational modification (PTM) in human
      pathology and other biochemical contexts. In order to perform characterization of
      protein deamidation, we have recently developed a novel long-length electrostatic
      repulsion-hydrophilic interaction chromatography-tandem mass spectrometry (LERLIC
      MS/MS) method which can separate the glutamine (Gln) and asparagine (Asn) isoform
      products of deamidation from model compounds to highly complex biological
      samples. LERLIC-MS/MS is, therefore, the first shotgun proteomics strategy for
      the separation and quantification of Gln deamidation isoforms. We also
      demonstrate, as a novelty, that the sample processing protocol outlined here
      stabilizes the succinimide intermediate allowing its characterization by LERLIC
      MS/MS. Application of LERLIC-MS/MS as shown in this video article can help to
      elucidate the currently unknown molecular arrays of protein deamidation.
      Additionally, LERLIC-MS/MS provides further understanding of the enzymatic
      reactions that encompass deamidation in distinct biological backgrounds.

PMID- 28448027
TI  - Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice
      Using a Nose-only Exposure System.
AB  - Obstructive respiratory diseases like asthma and chronic obstructive pulmonary
      disease (COPD) are currently treated by inhaled anti-inflammatory and
      bronchodilator drugs. Despite the availability of multiple treatments, both
      diseases are growing public health concerns. The majority of asthma patients are
      well controlled on current inhaled therapies but a substantial number of patients
      with severe asthma are not. Asthma affects an estimated 300 million people
      worldwide and approximately 20 percent have a severe form of the disease. In
      contrast to asthma, there are few effective therapies for COPD. An estimated 10%
      of the population has COPD and the trend in death rates is increasing for COPD
      while decreasing for other major diseases. Although developing drugs for inhaled
      delivery is challenging, the nose-only inhalation unit enables direct delivery of
      novel drugs to the lung of rodents for pre-clinical efficacy and
      safety/toxicology studies. Inhaled drug delivery has multiple advantages for
      respiratory diseases, where high concentration in the lung improves efficacy and
      minimizes systemic side effects. Inhaled corticosteroids and bronchodilators
      benefit from these advantages and inhaled delivery may also hold potential for
      future biologic therapies. The inhalation unit described herein can generate,
      sample for characterization, and uniformly deposit a drug aerosol in the lungs of
      rodents. This enables the pre-clinical determination of the efficacy and safety
      of drug doses deposited in the lungs of rodents, key data required before
      initiating clinical development.

PMID- 28448028
TI  - System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting
      Intracellular Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a
      leading cause of morbidity and mortality worldwide. With the increased spread of
      multi drug-resistant TB (MDR-TB), there is a real urgency to develop new
      therapeutic strategies against M. tuberculosis infections. Traditionally,
      compounds are evaluated based on their antibacterial activity under in vitro
      growth conditions in broth; however, results are often misleading for
      intracellular pathogens like M. tuberculosis since in-broth phenotypic screening
      conditions are significantly different from the actual disease conditions within
      the human body. Screening for inhibitors that work inside macrophages has been
      traditionally difficult due to the complexity, variability in infection, and slow
      replication rate of M. tuberculosis. In this study, we report a new approach to
      rapidly assess the effectiveness of compounds on the viability of M. tuberculosis
      in a macrophage infection model. Using a combination of a cytotoxicity assay and
      an in-broth M. tuberculosis viability assay, we were able to create a screening
      system that generates a comprehensive analysis of compounds of interest. This
      system is capable of producing quantitative data at a low cost that is within
      reach of most labs and yet is highly scalable to fit large industrial settings.

PMID- 28448029
TI  - Gain-compensation Methodology for a Sinusoidal Scan of a Galvanometer Mirror in
      Proportional-Integral-Differential Control Using Pre-emphasis Techniques.
AB  - Galvanometer mirrors are used for optical applications such as target tracking,
      drawing, and scanning control because of their high speed and accuracy. However,
      the responsiveness of a galvanometer mirror is limited by its inertia; hence, the
      gain of a galvanometer mirror is reduced when the control path is steep. In this
      research, we propose a method to extend the corresponding frequency using a pre
      emphasis technique to compensate for the gain reduction of galvanometer mirrors
      in sine-wave path tracking using proportional-integral-differential (PID)
      control. The pre-emphasis technique obtains an input value for a desired output
      value in advance. Applying this method to control the galvanometer mirror, the
      raw gain of a galvanometer mirror in each frequency and amplitude for sine-wave
      path tracking using a PID controller was calculated. Where PID control is not
      effective, maintaining a gain of 0 dB to improve the trajectory tracking
      accuracy, it is possible to expand the speed range in which a gain of 0 dB can be
      obtained without tuning the PID control parameters. However, if there is only one
      frequency, amplification is possible with a single pre-emphasis coefficient.
      Therefore, a sine wave is suitable for this technique, unlike triangular and
      sawtooth waves. Hence, we can adopt a pre-emphasis technique to configure the
      parameters in advance, and we need not prepare additional active control models
      and hardware. The parameters are updated immediately within the next cycle
      because of the open loop after the pre-emphasis coefficients are set. In other
      words, to regard the controller as a black box, we need to know only the input-to
      output ratio, and detailed modeling is not required. This simplicity allows our
      system to be easily embedded in applications. Our method using the pre-emphasis
      technique for a motion-blur compensation system and the experiment conducted to
      evaluate the method are explained.

PMID- 28448030
TI  - Synthesis of Biocompatible Liquid Crystal Elastomer Foams as Cell Scaffolds for
      3D Spatial Cell Cultures.
AB  - Here, we present a step-by-step preparation of a 3D, biodegradable, foam-like
      cell scaffold. These scaffolds were prepared by cross-linking star block co
      polymers featuring cholesterol units as side-chain pendant groups, resulting in
      smectic-A (SmA) liquid crystal elastomers (LCEs). Foam-like scaffolds, prepared
      using metal templates, feature interconnected microchannels, making them suitable
      as 3D cell culture scaffolds. The combined properties of the regular structure of
      the metal foam and of the elastomer result in a 3D cell scaffold that promotes
      not only higher cell proliferation compared to conventional porous templated
      films, but also better management of mass transport (i.e., nutrients, gases,
      waste, etc.). The nature of the metal template allows for the easy manipulation
      of foam shapes (i.e., rolls or films) and for the preparation of scaffolds of
      different pore sizes for different cell studies while preserving the
      interconnected porous nature of the template. The etching process does not affect
      the chemistry of the elastomers, preserving their biocompatible and biodegradable
      nature. We show that these smectic LCEs, when grown for extensive time periods,
      enable the study of clinically relevant and complex tissue constructs while
      promoting the growth and proliferation of cells.

PMID- 28448031
TI  - Transcriptomic Analysis of C. elegans RNA Sequencing Data Through the Tuxedo
      Suite on the Galaxy Project.
AB  - Next generation sequencing (NGS) technologies have revolutionized the nature of
      biological investigation. Of these, RNA Sequencing (RNA-Seq) has emerged as a
      powerful tool for gene-expression analysis and transcriptome mapping. However,
      handling RNA-Seq datasets requires sophisticated computational expertise and
      poses inherent challenges for biology researchers. This bottleneck has been
      mitigated by the open access Galaxy project that allows users without
      bioinformatics skills to analyze RNA-Seq data, and the Database for Annotation,
      Visualization, and Integrated Discovery (DAVID), a Gene Ontology (GO) term
      analysis suite that helps derive biological meaning from large data sets.
      However, for first-time users and bioinformatics' amateurs, self-learning and
      familiarization with these platforms can be time-consuming and daunting. We
      describe a straightforward workflow that will help C. elegans researchers to
      isolate worm RNA, conduct an RNA-Seq experiment and analyze the data using Galaxy
      and DAVID platforms. This protocol provides stepwise instructions for using the
      various Galaxy modules for accessing raw NGS data, quality-control checks,
      alignment, and differential gene expression analysis, guiding the user with
      parameters at every step to generate a gene list that can be screened for
      enrichment of gene classes or biological processes using DAVID. Overall, we
      anticipate that this article will provide information to C. elegans researchers
      undertaking RNA-Seq experiments for the first time as well as frequent users
      running a small number of samples.

PMID- 28448032
TI  - A Tailored HPLC Purification Protocol That Yields High-purity Amyloid Beta 42 and
      Amyloid Beta 40 Peptides, Capable of Oligomer Formation.
AB  - Amyloidogenic peptides such as the Alzheimer's disease-implicated Amyloid beta
      (Abeta), can present a significant challenge when trying to obtain high purity
      material. Here we present a tailored HPLC purification protocol to produce high
      purity amyloid beta 42 (Abeta42) and amyloid beta 40 (Abeta40) peptides. We have
      found that the combination of commercially available hydrophobic
      poly(styrene/divinylbenzene) stationary phase, polymer laboratory reverse phase -
      styrenedivinylbenzene (PLRP-S) under high pH conditions, enables the attainment
      of high purity (>95%) Abeta42 in a single chromatographic run. The purification
      is highly reproducible and can be amended to both semi-preparative and analytical
      conditions depending upon the amount of material wished to be purified. The
      protocol can also be applied to the Abeta40 peptide with identical success and
      without the need to alter the method.

PMID- 28448033
TI  - Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of
      Acid-labile Protecting Groups.
AB  - Unnatural amino acids, amino acids containing side-chain functionalities not
      commonly seen in nature, are increasingly found in synthetic peptide sequences.
      Synthesis of some unnatural amino acids often includes the use of a precursor
      consisting of a Schiff-base stabilized by a nickel cation. Unnatural side-chains
      can be installed on an amino acid backbone found in this Schiff-base complex. The
      resulting unnatural amino acid can then be isolated from this complex using
      hydrolysis of the Schiff-base, typically by employing reflux in strongly acidic
      solution. These highly acidic conditions may remove acid-labile side-chain
      protecting groups necessary for the unnatural amino acids to be used in microwave
      assisted solid-phase peptide synthesis. In this work, we present an efficient
      hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni
      Schiff base complex. Hydrolysis conditions presented in this work are suitable
      for retention of acid-labile side-chain protecting groups and may be adaptable to
      a variety of unnatural amino acid substrates.

PMID- 28448034
TI  - Using a Fluorescent PCR-capillary Gel Electrophoresis Technique to Genotype
      CRISPR/Cas9-mediated Knockout Mutants in a High-throughput Format.
AB  - The development of programmable genome-editing tools has facilitated the use of
      reverse genetics to understand the roles specific genomic sequences play in the
      functioning of cells and whole organisms. This cause has been tremendously aided
      by the recent introduction of the CRISPR/Cas9 system-a versatile tool that allows
      researchers to manipulate the genome and transcriptome in order to, among other
      things, knock out, knock down, or knock in genes in a targeted manner. For the
      purpose of knocking out a gene, CRISPR/Cas9-mediated double-strand breaks recruit
      the non-homologous end-joining DNA repair pathway to introduce the frameshift
      causing insertion or deletion of nucleotides at the break site. However, an
      individual guide RNA may cause undesirable off-target effects, and to rule these
      out, the use of multiple guide RNAs is necessary. This multiplicity of targets
      also means that a high-volume screening of clones is required, which in turn begs
      the use of an efficient high-throughput technique to genotype the knockout
      clones. Current genotyping techniques either suffer from inherent limitations or
      incur high cost, hence rendering them unsuitable for high-throughput purposes.
      Here, we detail the protocol for using fluorescent PCR, which uses genomic DNA
      from crude cell lysate as a template, and then resolving the PCR fragments via
      capillary gel electrophoresis. This technique is accurate enough to differentiate
      one base-pair difference between fragments and hence is adequate in indicating
      the presence or absence of a frameshift in the coding sequence of the targeted
      gene. This precise knowledge effectively precludes the need for a confirmatory
      sequencing step and allows users to save time and cost in the process. Moreover,
      this technique has proven to be versatile in genotyping various mammalian cells
      of various tissue origins targeted by guide RNAs against numerous genes, as shown
      here and elsewhere.

PMID- 28448035
TI  - Bioluminescence Imaging of Neuroinflammation in Transgenic Mice After Peripheral
      Inoculation of Alpha-Synuclein Fibrils.
AB  - To study the prion-like behavior of misfolded alpha-synuclein, mouse models are
      needed that allow fast and simple transmission of alpha-synuclein prionoids,
      which cause neuropathology within the central nervous system (CNS). Here we
      describe that intraglossal or intraperitoneal injection of alpha-synuclein
      fibrils into bigenic Tg(M83+/-:Gfap-luc+/-) mice, which overexpress human alpha
      synuclein with the A53T mutation from the prion protein promoter and firefly
      luciferase from the promoter for glial fibrillary acidic protein (Gfap), is
      sufficient to induce neuropathologic disease. In comparison to homozygous
      Tg(M83+/+) mice that develop severe neurologic symptoms beginning at an age of 8
      months, heterozygous Tg(M83+/-:Gfap-luc+/-) animals remain free of spontaneous
      disease until they reach an age of 22 months. Interestingly, injection of alpha
      synuclein fibrils via the intraperitoneal route induced neurologic disease with
      paralysis in four of five Tg(M83+/-:Gfap-luc+/-) mice with a median incubation
      time of 229 +/-17 days. Diseased animals showed severe deposits of phosphorylated
      alpha-synuclein in their brains and spinal cords. Accumulations of alpha
      synuclein were sarkosyl-insoluble and colocalized with ubiquitin and p62, and
      were accompanied by an inflammatory response resulting in astrocytic gliosis and
      microgliosis. Surprisingly, inoculation of alpha-synuclein fibrils into the
      tongue was less effective in causing disease with only one of five injected
      animals showing alpha-synuclein pathology after 285 days. Our findings show that
      inoculation via the intraglossal route and more so via the intraperitoneal route
      is suitable to induce neurologic illness with relevant hallmarks of
      synucleinopathies in Tg(M83+/-:Gfap-luc+/-) mice. This provides a new model for
      studying prion-like pathogenesis induced by alpha-synuclein prionoids in greater
      detail.

PMID- 28448037
TI  - Cooling an Optically Trapped Ultracold Fermi Gas by Periodical Driving.
AB  - We present a cooling method for a cold Fermi gas by parametrically driving atomic
      motions in a crossed-beam optical dipole trap (ODT). Our method employs the
      anharmonicity of the ODT, in which the hotter atoms at the edge of the trap feel
      the anharmonic components of the trapping potential, while the colder atoms in
      the center of the trap feel the harmonic one. By modulating the trap depth with
      frequencies that are resonant with the anharmonic components, we selectively
      excite the hotter atoms out of the trap while keeping the colder atoms in the
      trap, generating parametric cooling. This experimental protocol starts with a
      magneto-optical trap (MOT) that is loaded by a Zeeman slower. The precooled atoms
      in the MOT are then transferred to an ODT, and a bias magnetic field is applied
      to create an interacting Fermi gas. We then lower the trapping potential to
      prepare a cold Fermi gas near the degenerate temperature. After that, we sweep
      the magnetic field to the noninteracting regime of the Fermi gas, in which the
      parametric cooling can be manifested by modulating the intensity of the optical
      trapping beams. We find that the parametric cooling effect strongly depends on
      the modulation frequencies and amplitudes. With the optimized frequency and
      amplitude, we measure the dependence of the cloud energy on the modulation time.
      We observe that the cloud energy is changed in an anisotropic way, where the
      energy of the axial direction is significantly reduced by parametric driving. The
      cooling effect is limited to the axial direction because the dominant
      anharmonicity of the crossed-beam ODT is along the axial direction. Finally, we
      propose to extend this protocol for the trapping potentials of large
      anharmonicity in all directions, which provides a promising scheme for cooling
      quantum gases using external driving.

PMID- 28448036
TI  - Using Microfluidic Devices to Measure Lifespan and Cellular Phenotypes in Single
      Budding Yeast Cells.
AB  - Budding yeast Saccharomyces cerevisiae is an important model organism in aging
      research. Genetic studies have revealed many genes with conserved effects on the
      lifespan across species. However, the molecular causes of aging and death remain
      elusive. To gain a systematic understanding of the molecular mechanisms
      underlying yeast aging, we need high-throughput methods to measure lifespan and
      to quantify various cellular and molecular phenotypes in single cells.
      Previously, we developed microfluidic devices to track budding yeast mother cells
      throughout their lifespan while flushing away newborn daughter cells. This
      article presents a method for preparing microfluidic chips and for setting up
      microfluidic experiments. Multiple channels can be used to simultaneously track
      cells under different conditions or from different yeast strains. A typical setup
      can track hundreds of cells per channel and allow for high-resolution microscope
      imaging throughout the lifespan of the cells. Our method also allows detailed
      characterization of the lifespan, molecular markers, cell morphology, and the
      cell cycle dynamics of single cells. In addition, our microfluidic device is able
      to trap a significant amount of fresh mother cells that can be identified by
      downstream image analysis, making it possible to measure the lifespan with higher
      accuracy.

PMID- 28448038
TI  - Preparation of Non-human Primate Brain Tissue for Pre-embedding
      Immunohistochemistry and Electron Microscopy.
AB  - Despite all the technological advances at the light microscopy level, electron
      microscopy remains the only tool in neuroscience to examine and characterize
      ultrastructural and morphological details of neurons, such as synaptic contacts.
      Good preservation of brain tissue for electron microscopy can be obtained by
      rigorous cryo-fixation methods, but these techniques are rather costly and limit
      the use of immunolabeling, which is crucial to understand the connectivity of
      identified neuronal systems. Freeze-substitution methods have been developed to
      allow the combination of cryo-fixation with immunolabeling. However, the
      reproducibility of these methodological approaches usually relies on costly
      freezing devices. Moreover, achieving reliable results with this technique is
      very time-consuming and skill-challenging. Hence, the traditional chemically
      fixed brain, particularly with acrolein fixative, remains a time-efficient and
      low-cost method to combine electron microscopy with immunohistochemistry. Here,
      we provide a reliable experimental protocol using chemical acrolein fixation that
      leads to the preservation of primate brain tissue and is compatible with pre
      embedding immunohistochemistry and transmission electron microscopic examination.

PMID- 28448039
TI  - Surgical Ablation Assay for Studying Eye Regeneration in Planarians.
AB  - In the study of adult stem cells and regenerative mechanisms, planarian flatworms
      are a staple in vivo model system. This is due in large part to their abundant
      pluripotent stem cell population and ability to regenerate all cell and tissue
      types after injuries that would be catastrophic for most animals. Recently,
      planarians have gained popularity as a model for eye regeneration. Their ability
      to regenerate the entire eye (comprised of two tissue types: pigment cells and
      photoreceptors) allows for the dissection of the mechanisms regulating visual
      system regeneration. Eye ablation has several advantages over other techniques
      (such as decapitation or hole punch) for examining eye-specific pathways and
      mechanisms, the most important of which is that regeneration is largely
      restricted to eye tissues alone. The purpose of this video article is to
      demonstrate how to reliably remove the planarian optic cup without disturbing the
      brain or surrounding tissues. The handling of worms and maintenance of an
      established colony is also described. This technique uses a 31 G, 5/16-inch
      insulin needle to surgically scoop out the optic cup of planarians immobilized on
      a cold plate. This method encompasses both single and double eye ablation, with
      eyes regenerating within 1-2 weeks, allowing for a wide range of applications. In
      particular, this ablation technique can be easily combined with pharmacological
      and genetic (RNA interference) screens for a better understanding of regenerative
      mechanisms and their evolution, eye stem cells and their maintenance, and
      phototaxic behavioral responses and their neurological basis.

PMID- 28448040
TI  - Determination of High-affinity Antibody-antigen Binding Kinetics Using Four
      Biosensor Platforms.
AB  - Label-free optical biosensors are powerful tools in drug discovery for the
      characterization of biomolecular interactions. In this study, we describe the use
      of four routinely used biosensor platforms in our laboratory to evaluate the
      binding affinity and kinetics of ten high-affinity monoclonal antibodies (mAbs)
      against human proprotein convertase subtilisin kexin type 9 (PCSK9). While both
      Biacore T100 and ProteOn XPR36 are derived from the well-established Surface
      Plasmon Resonance (SPR) technology, the former has four flow cells connected by
      serial flow configuration, whereas the latter presents 36 reaction spots in
      parallel through an improvised 6 x 6 crisscross microfluidic channel
      configuration. The IBIS MX96 also operates based on the SPR sensor technology,
      with an additional imaging feature that provides detection in spatial
      orientation. This detection technique coupled with the Continuous Flow
      Microspotter (CFM) expands the throughput significantly by enabling multiplex
      array printing and detection of 96 reaction sports simultaneously. In contrast,
      the Octet RED384 is based on the BioLayer Interferometry (BLI) optical principle,
      with fiber-optic probes acting as the biosensor to detect interference pattern
      changes upon binding interactions at the tip surface. Unlike the SPR-based
      platforms, the BLI system does not rely on continuous flow fluidics; instead, the
      sensor tips collect readings while they are immersed in analyte solutions of a
      384-well microplate during orbital agitation. Each of these biosensor platforms
      has its own advantages and disadvantages. To provide a direct comparison of these
      instruments' ability to provide quality kinetic data, the described protocols
      illustrate experiments that use the same assay format and the same high-quality
      reagents to characterize antibody-antigen kinetics that fit the simple 1:1
      molecular interaction model.

PMID- 28448041
TI  - Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I
      Metabolic Competency of In Vitro Cell Cultures.
AB  - Xenobiotic metabolizing enzymes play a key function in the biotransformation of
      medicines and toxicants by adding functional groups that increase solubility and
      facilitate excretion. On some occasions those structural modifications lead to
      the formation of new toxic products. In order to reduce animal testing, chemical
      risk can be assessed using metabolically competent cells. The expression of
      metabolic enzymes, however, is not stable over time in many in vitro primary
      culture systems and is often partial or absent in cell lines. Therefore, the
      study of medicines, additives, and environmental pollutants metabolism in vitro
      should ideally be conducted in cell systems where metabolic activity has been
      characterized. We explain here an approach to measure the activity of a class of
      metabolic enzymes (Human Phase I) in 2D cell lines and primary 3D cultures using
      chemical probes and their metabolic products quantifiable by UPLC mass
      spectrometry and luminometry. The method can be implemented to test the metabolic
      activity in cell lines and primary cells derived from a variety of tissues.

PMID- 28448042
TI  - Imaging the Neutrophil Phagosome and Cytoplasm Using a Ratiometric pH Indicator.
AB  - Neutrophils are crucial to host innate defense and, consequently, constitute an
      important area of medical research. The phagosome, the intracellular compartment
      where the killing and digestion of engulfed particles take place, is the main
      arena for neutrophil pathogen killing that requires tight regulation. Phagosomal
      pH is one aspect that is carefully controlled, in turn regulating antimicrobial
      protease activity. Many fluorescent pH-sensitive dyes have been used to visualize
      the phagosomal environment. S-1 has several advantages over other pH-sensitive
      dyes, including its dual emission spectra, its resistance to photo-bleaching, and
      its high pKa. Using this method, we have demonstrated that the neutrophil
      phagosome is unusually alkaline in comparison to other phagocytes. By using
      different biochemical conjugations of the dye, the phagosome can be delineated
      from the cytoplasm so that changes in the size and shape of the phagosome can be
      assessed. This allows for further monitoring of ionic movement.

PMID- 28448043
TI  - Challenges in Rheological Characterization of Highly Concentrated Suspensions - A
      Case Study for Screen-printing Silver Pastes.
AB  - A comprehensive rheological characterization of highly concentrated suspensions
      or pastes is mandatory for a targeted product development meeting the manifold
      requirements during processing and application of such complex fluids. In this
      investigation, measuring protocols for a conclusive assessment of different
      process relevant rheological parameters have been evaluated. This includes the
      determination of yield stress, viscosity, wall slip velocity, structural recovery
      after large deformation and elongation at break as well as tensile force during
      filament stretching. The importance of concomitant video recordings during
      parallel-plate rotational rheometry for a significant determination of
      rheological quantities is demonstrated. The deformation profile and flow field at
      the sample edge can be determined using appropriate markers. Thus, measurement
      parameter settings and plate roughness values can be identified for which yield
      stress and viscosity measurements are possible. Slip velocity can be measured
      directly and measuring conditions at which plug flow, shear banding or sample
      spillover occur can be identified clearly. Video recordings further confirm that
      the change in shear moduli observed during three stage oscillatory shear tests
      with small deformation amplitude in stage I and III but large oscillation
      amplitude in stage II can be directly attributed to structural break down and
      recovery. For the pastes investigated here, the degree of irreversible, shear
      induced structural change increases with increasing deformation amplitude in
      stage II until a saturation is reached at deformations corresponding to the
      crossover of G' and G'', but the irreversible damage is independent of the
      duration of large amplitude shear. A capillary breakup elongational rheometer and
      a tensile tester have been used to characterize deformation and breakup behavior
      of highly filled pastes in uniaxial elongation. Significant differences were
      observed in all experiments described above for two commercial screen-printing
      silver pastes used for front side metallization of Si-solar cells.

PMID- 28448044
TI  - Generation of iPSC-derived Human Brain Organoids to Model Early
      Neurodevelopmental Disorders.
AB  - The restricted availability of suitable in vitro models that can reliably
      represent complex human brain development is a significant bottleneck that limits
      the translation of basic brain research into clinical application. While induced
      pluripotent stem cells (iPSCs) have replaced the ethically questionable human
      embryonic stem cells, iPSC-based neuronal differentiation studies remain
      descriptive at the cellular level but fail to adequately provide the details that
      could be derived from a complex, 3D human brain tissue. This gap is now filled
      through the application of iPSC-derived, 3D brain organoids, "Brains in a dish,"
      that model many features of complex human brain development. Here, a method for
      generating iPSC-derived, 3D brain organoids is described. The organoids can help
      with modeling autosomal recessive primary microcephaly (MCPH), a rare human
      neurodevelopmental disorder. A widely accepted explanation for the brain
      malformation in MCPH is a depletion of the neural stem cell pool during the early
      stages of human brain development, a developmental defect that is difficult to
      recreate or prove in vitro. To study MCPH, we generated iPSCs from patient
      derived fibroblasts carrying a mutation in the centrosomal protein CPAP. By
      analyzing the ventricular zone of microcephaly 3D brain organoids, we showed the
      premature differentiation of neural progenitors. These 3D brain organoids are a
      powerful in vitro system that will be instrumental in modeling congenital brain
      disorders induced by neurotoxic chemicals, neurotrophic viral infections, or
      inherited genetic mutations.

PMID- 28448045
TI  - Fluorescence-based Neuraminidase Inhibition Assay to Assess the Susceptibility of
      Influenza Viruses to The Neuraminidase Inhibitor Class of Antivirals.
AB  - The neuraminidase (NA) inhibitors are the only class of antivirals approved for
      the treatment and prophylaxis of influenza that are effective against currently
      circulating strains. In addition to their use in treating seasonal influenza, the
      NA inhibitors have been stockpiled by a number of countries for use in the event
      of a pandemic. It is therefore important to monitor the susceptibility of
      circulating influenza viruses to this class of antivirals. There are different
      types of assays that can be used to assess the susceptibility of influenza
      viruses to the NA inhibitors, but the enzyme inhibition assays using either a
      fluorescent substrate or a chemiluminescent substrate are the most widely used
      and recommended. This protocol describes the use of a fluorescence-based assay to
      assess influenza virus susceptibility to NA inhibitors. The assay is based on the
      NA enzyme cleaving the 2'-(4-Methylumbelliferyl)-alpha-D-N-acetylneuraminic acid
      (MUNANA) substrate to release the fluorescent product 4-methylumbelliferone (4
      MU). Therefore, the inhibitory effect of an NA inhibitor on the influenza virus
      NA is determined based on the concentration of the NA inhibitor that is required
      to reduce 50% of the NA activity, given as an IC50 value.

PMID- 28448046
TI  - A Novel Technique for Raman Analysis of Highly Radioactive Samples Using Any
      Standard Micro-Raman Spectrometer.
AB  - A novel approach for the Raman measurement of nuclear materials is reported in
      this paper. It consists of the enclosure of the radioactive sample in a tight
      capsule that isolates the material from the atmosphere. The capsule can
      optionally be filled with a chosen gas pressurized up to 20 bars. The micro-Raman
      measurement is performed through an optical-grade quartz window. This technique
      permits accurate Raman measurements with no need for the spectrometer to be
      enclosed in an alpha-tight containment. It therefore allows the use of all
      options of the Raman spectrometer, like multi-wavelength laser excitation,
      different polarizations, and single or triple spectrometer modes. Some examples
      of measurements are shown and discussed. First, some spectral features of a
      highly radioactive americium oxide sample (AmO2) are presented. Then, we report
      the Raman spectra of neptunium oxide (NpO2) samples, the interpretation of which
      is greatly improved by employing three different excitation wavelengths, 17O
      doping, and a triple mode configuration to measure the anti-stokes Raman lines.
      This last feature also allows the estimation of the sample surface temperature.
      Finally, data that were measured on a sample from Chernobyl lava, where phases
      are identified by Raman mapping, are shown.

PMID- 28448047
TI  - A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and
      Longitudinal Assessment of Preclinical Therapies.
AB  - Renal cell carcinoma (RCC) affects > 60,000 people in the United States annually,
      and ~ 30% of RCC patients have multiple metastases at the time of diagnosis.
      Metastatic RCC (mRCC) is incurable, with a median survival time of only 18
      months. Immune-based interventions (e.g., interferon (IFN) and interleukin (IL)
      2) induce durable responses in a fraction of mRCC patients, and multikinase
      inhibitors (e.g., sunitinib or sorafenib) or anti-VEGF receptor monoclonal
      antibodies (mAb) are largely palliative, as complete remissions are rare. Such
      shortcomings in current therapies for mRCC patients provide the rationale for the
      development of novel treatment protocols. A key component in the preclinical
      testing of new therapies for mRCC is a suitable animal model. Beneficial features
      that recapitulate the human condition include a primary renal tumor, renal tumor
      metastases, and an intact immune system to investigate any therapy-driven immune
      effector responses and the formation of tumor-induced immunosuppressive factors.
      This report describes an orthotopic mRCC mouse model that has all of these
      features. We describe an intrarenal implantation technique using the mouse renal
      adenocarcinoma cell line Renca, followed by the assessment of tumor growth in the
      kidney (primary site) and lungs (metastatic site).

PMID- 28448048
TI  - Time-resolved ElectroSpray Ionization Hydrogen-deuterium Exchange Mass
      Spectrometry for Studying Protein Structure and Dynamics.
AB  - Intrinsically disordered proteins (IDPs) have long been a challenge to structural
      biologists due to their lack of stable secondary structure elements. Hydrogen
      Deuterium Exchange (HDX) measured at rapid time scales is uniquely suited to
      detect structures and hydrogen bonding networks that are briefly populated,
      allowing for the characterization of transient conformers in native ensembles.
      Coupling of HDX to mass spectrometry offers several key advantages, including
      high sensitivity, low sample consumption and no restriction on protein size. This
      technique has advanced greatly in the last several decades, including the ability
      to monitor HDX labeling times on the millisecond time scale. In addition, by
      incorporating the HDX workflow onto a microfluidic platform housing an acidic
      protease microreactor, we are able to localize dynamic properties at the peptide
      level. In this study, Time-Resolved ElectroSpray Ionization Mass Spectrometry
      (TRESI-MS) coupled to HDX was used to provide a detailed picture of residual
      structure in the tau protein, as well as the conformational shifts induced upon
      hyperphosphorylation.

PMID- 28448049
TI  - Controlled-release of Chlorine Dioxide in a Perforated Packaging System to Extend
      the Storage Life and Improve the Safety of Grape Tomatoes.
AB  - A controlled-release chlorine dioxide (ClO2) pouch was developed by sealing a
      slurry form of ClO2 into semipermeable polymer film; the release properties of
      the pouch were monitored in containers with or without fruit. The pouch was
      affixed to the inside of a perforated clamshell containing grape tomatoes, and
      the effect on microbial population, firmness, and weight loss was evaluated
      during a 14 day storage period at 20  degrees C. Within 3 days, the ClO2
      concentration in the clamshells reached 3.5 ppm and remained constant until day
      10. Thereafter, it decreased to 2 ppm by day 14. The ClO2 pouch exhibited strong
      antimicrobial activity, reducing Escherichia coli populations by 3.08 log CFU/g
      and Alternaria alternata populations by 2.85 log CFU/g after 14 days of storage.
      The ClO2 treatment also reduced softening and weight loss and extended the
      overall shelf life of the tomatoes. Our results suggest that ClO2 treatment is
      useful for extending the shelf life and improving the microbial safety of
      tomatoes during storage without impairing their quality.

PMID- 28448050
TI  - Single Molecule Analysis of Laser Localized Psoralen Adducts.
AB  - The DNA Damage Response (DDR) has been extensively characterized in studies of
      double strand breaks (DSBs) induced by laser micro beam irradiation in live
      cells. The DDR to helix distorting covalent DNA modifications, including
      interstrand DNA crosslinks (ICLs), is not as well defined. We have studied the
      DDR stimulated by ICLs, localized by laser photoactivation of immunotagged
      psoralens, in the nuclei of live cells. In order to address fundamental questions
      about adduct distribution and replication fork encounters, we combined laser
      localization with two other technologies. DNA fibers are often used to display
      the progress of replication forks by immunofluorescence of nucleoside analogues
      incorporated during short pulses. Immunoquantum dots have been widely employed
      for single molecule imaging. In the new approach, DNA fibers from cells carrying
      laser localized ICLs are spread onto microscope slides. The tagged ICLs are
      displayed with immunoquantum dots and the inter-lesion distances determined.
      Replication fork collisions with ICLs can be visualized and different encounter
      patterns identified and quantitated.

PMID- 28448051
TI  - Protocols for Investigating the Host-tissue Distribution, Transmission-mode, and
      Effect on the Host Fitness of a Densovirus in the Cotton Bollworm.
AB  - Many novel viruses have been discovered in animal hosts using next-generation
      sequencing technologies. Previously, we reported a mutualistic virus, Helicoverpa
      armigera densovirus (HaDV2), in a lepidopteran species, the cotton bollworm,
      Helicoverpa armigera (Hubner). Here, we describe the protocols that are currently
      used to study the effect of HaDV2 on its host. First, we establish a HaDV2-free
      cotton bollworm colony from a single breeding pair. Then, we orally inoculate
      some neonate larval offspring with HaDV2-containing filtered liquid to produce
      two colonies with the same genetic background: one HaDV2-infected, the other
      uninfected. A protocol to compare life table parameters (e.g., larval, pupal, and
      adult periods and fecundity) between the HaDV2-infected and -uninfected
      individuals is also presented, as are the protocols for determining the host
      tissue distribution and transmission efficiency of HaDV2. These protocols would
      also be suitable for investigating the effects of other orally transmitted
      viruses on their insect hosts, lepidopteran hosts in particular.

PMID- 28448052
TI  - An In Vitro Organ Culture Model of the Murine Intervertebral Disc.
AB  - Intervertebral disc (IVD) degeneration is a significant contributor to low back
      pain. The IVD is a fibrocartilaginous joint that serves to transmit and dampen
      loads in the spine. The IVD consists of a proteoglycan-rich nucleus pulposus (NP)
      and a collagen-rich annulus fibrosis (AF) sandwiched by cartilaginous end-plates.
      Together with the adjacent vertebrae, the vertebrae-IVD structure forms a
      functional spine unit (FSU). These microstructures contain unique cell types as
      well as unique extracellular matrices. Whole organ culture of the FSU preserves
      the native extracellular matrix, cell differentiation phenotypes, and cellular
      matrix interactions. Thus, organ culture techniques are particularly useful for
      investigating the complex biological mechanisms of the IVD. Here, we describe a
      high-throughput approach for culturing whole lumbar mouse FSUs that provides an
      ideal platform for studying disease mechanisms and therapies for the IVD.
      Furthermore, we describe several applications that utilize this organ culture
      method to conduct further studies including contrast-enhanced microCT imaging and
      three-dimensional high-resolution finite element modeling of the IVD.

PMID- 28448053
TI  - Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug
      Safety Screening.
AB  - Cardiac tissue engineering describes techniques to constitute three dimensional
      force-generating engineered tissues. For the implementation of these procedures
      in basic research and preclinical drug development, it is important to develop
      protocols for automated generation and analysis under standardized conditions.
      Here, we present a technique to generate engineered heart tissue (EHT) from
      cardiomyocytes of different species (rat, mouse, human). The technique relies on
      the assembly of a fibrin-gel containing dissociated cardiomyocytes between
      elastic polydimethylsiloxane (PDMS) posts in a 24-well format. Three-dimensional,
      force-generating EHTs constitute within two weeks after casting. This procedure
      allows for the generation of several hundred EHTs per week and is technically
      limited only by the availability of cardiomyocytes (0.4-1.0 x 106/EHT).
      Evaluation of auxotonic muscle contractions is performed in a modified incubation
      chamber with a mechanical interlock for 24-well plates and a camera placed on top
      of this chamber. A software controls a camera moved on an XYZ axis system to each
      EHT. EHT contractions are detected by an automated figure recognition algorithm,
      and force is calculated based on shortening of the EHT and the elastic propensity
      and geometry of the PDMS posts. This procedure allows for automated analysis of
      high numbers of EHT under standardized and sterile conditions. The reliable
      detection of drug effects on cardiomyocyte contraction is crucial for cardiac
      drug development and safety pharmacology. We demonstrate, with the example of the
      hERG channel inhibitor E-4031, that the human EHT system replicates drug
      responses on contraction kinetics of the human heart, indicating it to be a
      promising tool for cardiac drug safety screening.

PMID- 28448055
TI  - Transient Expression and Cellular Localization of Recombinant Proteins in
      Cultured Insect Cells.
AB  - Heterologous protein expression systems are used for the production of
      recombinant proteins, the interpretation of cellular trafficking/localization,
      and the determination of the biochemical function of proteins at the sub
      organismal level. Although baculovirus expression systems are increasingly used
      for protein production in numerous biotechnological, pharmaceutical, and
      industrial applications, nonlytic systems that do not involve viral infection
      have clear benefits but are often overlooked and underutilized. Here, we describe
      a method for generating nonlytic expression vectors and transient recombinant
      protein expression. This protocol allows for the efficient cellular localization
      of recombinant proteins and can be used to rapidly discern protein trafficking
      within the cell. We show the expression of four recombinant proteins in a
      commercially available insect cell line, including two aquaporin proteins from
      the insect Bemisia tabaci, as well as subcellular marker proteins specific for
      the cell plasma membrane and for intracellular lysosomes. All recombinant
      proteins were produced as chimeras with fluorescent protein markers at their
      carboxyl termini, which allows for the direct detection of the recombinant
      proteins. The double transfection of cells with plasmids harboring constructs for
      the genes of interest and a known subcellular marker allows for live cell imaging
      and improved validation of cellular protein localization.

PMID- 28448054
TI  - Lipid Droplet Isolation for Quantitative Mass Spectrometry Analysis.
AB  - Lipid droplets are vital to the replication of a variety of different pathogens,
      most prominently the Hepatitis C Virus (HCV), as the putative site of virion
      morphogenesis. Quantitative lipid droplet proteome analysis can be used to
      identify proteins that localize to or are displaced from lipid droplets under
      conditions such as virus infections. Here, we describe a protocol that has been
      successfully used to characterize the changes in the lipid droplet proteome
      following infection with HCV. We use Stable Isotope Labeling with Amino Acids in
      Cell Culture (SILAC) and thus label the complete proteome of one population of
      cells with "heavy" amino acids to quantitate the proteins by mass spectrometry.
      For lipid droplet isolation, the two cell populations (i.e. HCV-infected/"light"
      amino acids and uninfected control/"heavy" amino acids) are mixed 1:1 and lysed
      mechanically in hypotonic buffer. After removing the nuclei and cell debris by
      low speed centrifugation, lipid droplet-associated proteins are enriched by two
      subsequent ultracentrifugation steps followed by three washing steps in isotonic
      buffer. The purity of the lipid droplet fractions is analyzed by western blotting
      with antibodies recognizing different subcellular compartments. Lipid droplet
      associated proteins are then separated by SDS-polyacrylamide gel electrophoresis
      (SDS-PAGE) followed by Coomassie staining. After tryptic digest, the peptides are
      quantified by liquid chromatography-electrospray ionization-tandem mass
      spectrometry (LC-ESI-MS/MS). Using this method, we identified proteins recruited
      to lipid droplets upon HCV infection that might represent pro- or antiviral host
      factors. Our method can be applied to a variety of different cells and culture
      conditions, such as infection with pathogens, environmental stress, or drug
      treatment.

PMID- 28448056
TI  - A Multi-hole Cryovial Eliminates Freezing Artifacts when Muscle Tissues are
      Directly Immersed in Liquid Nitrogen.
AB  - Studies on skeletal muscle physiology face the technical challenge of
      appropriately processing the specimens to obtain sections with clearly visible
      cytoplasmic compartments. Another hurdle is the tight apposition of myofibers to
      the surrounding tissues. Because the process of tissue fixation and paraffin
      embedding leads to the shrinkage of muscle fibers, freezing is an optimal means
      of hardening muscle tissue for sectioning. However, a commonly encountered issue,
      the formation of ice crystals, occurs during the preparation of frozen sections
      because of the high water content of muscle. The protocol presented here first
      describes a simple and efficient method for properly freezing muscle tissues by
      immersing them in liquid nitrogen. The problem with using liquid nitrogen alone
      is that it causes the formation of a nitrogen gas barrier next to the tissue,
      which acts as an insulator and inhibits the cooling of the tissues. To avoid this
      "vapor blanket" effect, a new cryovial was designed to increase the speed of
      liquid flow around the tissue surface. This was achieved by punching a total of
      14 inlet holes in the wall of the vial. According to bubble dynamics, a higher
      rate of liquid flow results in smaller bubbles and fewer chances to form a gas
      barrier. When liquid nitrogen flows into the cryovial through the inlet holes,
      the flow velocity around the tissue is fast enough to eliminate the gas barrier.
      Compared to the method of freezing muscle tissues using pre-chilled isopentane,
      this protocol is simpler and more efficient and can be used to freeze muscle in a
      throughput manner. Furthermore, this method is optimal for institutions that do
      not have access to isopentane, which is extremely flammable at room temperature.

PMID- 28448057
TI  - Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut
      Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells.
AB  - The gut is the largest endocrine organ of the body, with hormone-secreting
      enteroendocrine cells located along the length of the gastrointestinal
      epithelium. Despite their physiological importance, enteroendocrine cells
      represent only a small fraction of the epithelial cell population and in the
      past, their characterization has presented a considerable challenge resulting in
      a reliance on cell line models. Here, we provide a detailed protocol for the
      isolation and culture of mixed murine small intestinal cells. These primary
      cultures have been used to identify the signaling pathways underlying the
      stimulation and inhibition of gut peptide secretion in response to a number of
      nutrients and neuropeptides as well as pharmacological agents. Furthermore, in
      combination with the use of transgenic fluorescent reporter mice, we have
      demonstrated that these primary cultures become a powerful tool for the
      examination of fluorescently-tagged enteroendocrine cells at the intracellular
      level, using methods such as patch clamping and single-cell calcium and cAMP-FRET
      imaging.

PMID- 28448058
TI  - A Rapid Automated Protocol for Muscle Fiber Population Analysis in Rat Muscle
      Cross Sections Using Myosin Heavy Chain Immunohistochemistry.
AB  - Quantification of muscle fiber populations provides a deeper insight into the
      effects of disease, trauma, and various other influences on skeletal muscle
      composition. Various time-consuming methods have traditionally been used to study
      fiber populations in many fields of research. However, recently developed
      immunohistochemical methods based on myosin heavy chain protein expression
      provide a quick alternative to identify multiple fiber types in a single section.
      Here, we present a rapid, reliable and reproducible protocol for improved
      staining quality, allowing automatic acquisition of whole cross sections and
      automatic quantification of fiber populations with ImageJ. For this purpose,
      embedded skeletal muscles are cut in cross sections, stained using myosin heavy
      chains antibodies with secondary fluorescent antibodies and DAPI for cell nuclei
      staining. Whole cross sections are then scanned automatically using a slide
      scanner to obtain high-resolution composite pictures of the entire specimen.
      Fiber population analyses are subsequently performed to quantify slow,
      intermediate and fast fibers using an automated macro for ImageJ. We have
      previously shown that this method can identify fiber populations reliably to a
      degree of +/-4%. In addition, this method reduces inter-user variability and time
      per analyses significantly using the open source platform ImageJ.

PMID- 28448059
TI  - Pool-Boiling Heat-Transfer Enhancement on Cylindrical Surfaces with Hybrid
      Wettable Patterns.
AB  - In this study, pool-boiling heat-transfer experiments were performed to
      investigate the effect of the number of interlines and the orientation of the
      hybrid wettable pattern. Hybrid wettable patterns were produced by coating
      superhydrophilic SiO2 on a masked, hydrophobic, cylindrical copper surface. Using
      de-ionized (DI) water as the working fluid, pool-boiling heat-transfer studies
      were conducted on the different surface-treated copper cylinders of a 25-mm
      diameter and a 40-mm length. The experimental results showed that the number of
      interlines and the orientation of the hybrid wettable pattern influenced the wall
      superheat and the HTC. By increasing the number of interlines, the HTC was
      enhanced when compared to the plain surface. Images obtained from the charge
      coupled device (CCD) camera indicated that more bubbles formed on the interlines
      as compared to other parts. The hybrid wettable pattern with the lowermost
      section being hydrophobic gave the best heat-transfer coefficient (HTC). The
      experimental results indicated that the bubble dynamics of the surface is an
      important factor that determines the nucleate boiling.

PMID- 28448060
TI  - Small RNA Transfection in Primary Human Th17 Cells by Next Generation
      Electroporation.
AB  - CD4+ T cells can differentiate into several subsets of effector T helper cells
      depending on the surrounding cytokine milieu. Th17 cells can be generated from
      naive CD4+ T cells in vitro by activating them in the presence of the polarizing
      cytokines IL-1beta, IL-6, IL-23, and TGFbeta. Th17 cells orchestrate immunity
      against extracellular bacteria and fungi, but their aberrant activity has also
      been associated with several autoimmune and inflammatory diseases. Th17 cells are
      identified by the chemokine receptor CCR6 and defined by their master
      transcription factor, RORgammat, and characteristic effector cytokine, IL-17A.
      Optimized culture conditions for Th17 cell differentiation facilitate mechanistic
      studies of human T cell biology in a controlled environment. They also provide a
      setting for studying the importance of specific genes and gene expression
      programs through RNA interference or the introduction of microRNA (miRNA) mimics
      or inhibitors. This protocol provides an easy to use, reproducible, and highly
      efficient method for transient transfection of differentiating primary human Th17
      cells with small RNAs using a next generation electroporation device.

PMID- 28448061
TI  - Grand-maternal smoking in pregnancy and grandchild's autistic traits and
      diagnosed autism.
AB  - Although there is considerable research into the genetic background of autism
      spectrum disorders, environmental factors are likely to contribute to the
      variation in prevalence over time. Rodent experiments indicate that environmental
      exposures can have effects on subsequent generations, and human studies indicate
      that parental prenatal exposures may play a part in developmental variation. Here
      we use the Avon Longitudinal Study of Parents and Children (ALSPAC) to test the
      hypothesis that if the mother or father (F1) had been exposed to their own
      mother's (F0) smoking during pregnancy, the offspring (F2) would be at increased
      risk of autism. We find an association between maternal grandmother smoking in
      pregnancy and grand daughters having adverse scores in Social Communication and
      Repetitive Behaviour measures that are independently predictive of diagnosed
      autism. In line with this, we show an association with actual diagnosis of autism
      in her grandchildren. Paternal grandmothers smoking in pregnancy showed no
      associations.

PMID- 28448062
TI  - Association between small-for-gestational age and neurocognitive impairment at
      two years of corrected age among infants born at preterm gestational ages: a
      cohort study.
AB  - OBJECTIVE: To investigate the association between small-for-gestational age (SGA)
      and neurocognitive impairment at 2 years of corrected age among infants born at
      preterm gestational ages. STUDY DESIGN: A secondary analysis of a prospectively
      conducted NICHD/Maternal-Fetal Medicine Units BEAM trial. Non-anomalous
      pregnancies delivered before 37 weeks of gestation were included in the analysis.
      Neurocognitive outcomes at 2 years of corrected age were compared between infants
      who were SGA (<10% for gestational age) and those appropriately grown (AGA). The
      primary outcome was a severe or moderate neurocognitive impairment at 2 years of
      corrected age among survivors, defined as either mental (MDI) or psychomotor
      (PDI) developmental index score <70 for severe and <85 for moderate impairment.
      RESULTS: Of 2299 preterm neonates 67 (3%) were SGA. SGA infants were more often
      twin pregnancies (31% vs 17%, P=0.003) and delivered more often by cesarean
      section (63% vs 40%, P<0.001) at similar gestational ages (30.0+/-2.6 vs 29.5+/
      2.8 weeks, P=0.11). At 2 years of corrected age, SGA and AGA survivors had
      similar rates of neurocognitive impairment (MDI <70: 18% vs 18%, P=1.0; MDI <85:
      44% vs 46%, P=0.96; PDI <70: 20% vs 15%, P=0.51; PDI <85: 40% vs 34%, P=0.48).
      CONCLUSION: In this cohort, SGA at preterm gestational ages was associated with
      similar rates of neurocognitive impairment at two years of corrected age among
      surviving infants.

PMID- 28448063
TI  - Gonadotropin levels in urine during early postnatal period in small for
      gestational age preterm male infants with fetal growth restriction.
AB  - OBJECTIVE: The objective of this study was to estimate gonadotropin
      concentrations in small for gestational age (SGA) male infants with the
      reactivation of the hypothalamic-pituitary-gonadal axis during the first few
      months of life that is important for genital development. STUDY DESIGN: We
      prospectively examined 15 SGA and 15 appropriate for gestational age (AGA)
      preterm male infants between 2013 and 2014 at Kyoto University Hospital.
      Gonadotropin concentrations (luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH)) were measured in serial urine samples from the postnatal days 7 to
      168 and compared between SGA and AGA infants using the Mann-Whitney test.
      RESULTS: A longitudinal analysis showed that SGA infants had higher LH and lower
      FSH concentrations (P=0.004 and P=0.006, respectively) than AGA infants.
      CONCLUSION: Male infants who are SGA at birth because of fetal growth restriction
      have gonadotropin secretion abnormalities in the first few months of life.

PMID- 28448064
TI  - Changes in thyroid hormone concentrations during neonatal extracorporeal membrane
      oxygenation.
AB  - OBJECTIVE: Thyroid hormone concentrations can be disturbed during critical
      illness. Our aim was to determine changes in thyroid hormone concentrations
      during neonatal extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: We
      included 21 ECMO-treated neonates. Age-specific s.d. scores (SDS) of free and
      total thyroxine (FT4; TT4), reverse and total triiodothyronine (rT3; TT3),
      thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) were
      determined at six fixed time-points. Data were analyzed using general linear
      models. RESULTS: At baseline, mean SDS FT4 (-0.78, 95% CI: -1.37 to -0.19), TT4 (
      1.97, 95% CI: -2.76 to -1.18), TT3 (-0.88, 95% CI: -1.13 to -0.63), TSH (-2.14,
      95% CI: -2.93 to -1.35) and TBG (-3.52, 95% CI: -4.55 to -2.50) were low with
      high mean SDS rT3 (0.53, 95% CI: 0.28 to 0.78). One hour after start ECMO, TT4,
      TSH and TBG had further declined; 12 h after start ECMO TT3 had declined (all
      P<0.05). After this decline, mean SDS TSH increased to the baseline level 12 h
      after start ECMO (-2.50, 95% CI: -3.22 to -1.79), and was higher than baseline 48
      h after start ECMO (-0.56, 95% CI: -1.29 to 0.17). This TSH increase was followed
      by increases in TT4 and TT3. FT4 remained constant within the normal range during
      ECMO. CONCLUSIONS: Thyroid hormone concentrations before ECMO were suggestive of
      non-thyroidal illness syndrome (NTIS). During ECMO, increases in TSH, TT4 and TT3
      after an initial decline possibly reflect spontaneous restoration of the
      hypothalamic-pituitary-thyroid axis. FT4 remained constant within the normal
      range. This suggests that thyroxine therapy is not required during ECMO.

PMID- 28448067
TI  - Human T cell development notched up a level.

PMID- 28448066
TI  - Structural basis of CRISPR-SpyCas9 inhibition by an anti-CRISPR protein.
AB  - CRISPR-Cas9 systems are bacterial adaptive immune systems that defend against
      infection by phages. Through the RNA-guided endonuclease activity of Cas9 they
      degrade double-stranded DNA with a protospacer adjacent motif (PAM) and sequences
      complementary to the guide RNA. Recently, two anti-CRISPR proteins (AcrIIA2 and
      AcrIIA4 from Listeria monocytogenes prophages) were identified, both of which
      inhibit Streptococcus pyogenes Cas9 (SpyCas9) and L. monocytogenes Cas9 activity
      in bacteria and human cells. However, the mechanism of AcrIIA2- or AcrIIA4
      mediated Cas9 inhibition remains unknown. Here we report a crystal structure of
      SpyCas9 in complex with a single-guide RNA (sgRNA) and AcrIIA4. Our data show
      that AcrIIA2 and AcrIIA4 interact with SpyCas9 in a sgRNA-dependent manner. The
      structure reveals that AcrIIA4 inhibits SpyCas9 activity by structurally
      mimicking the PAM to occupy the PAM-interacting site in the PAM-interacting
      domain, thereby blocking recognition of double-stranded DNA substrates by
      SpyCas9. AcrIIA4 further inhibits the endonuclease activity of SpyCas9 by
      shielding its RuvC active site. Structural comparison reveals that formation of
      the AcrIIA4-binding site of SpyCas9 is induced by sgRNA binding. Our study
      reveals the mechanism of SpyCas9 inhibition by AcrIIA4, providing a structural
      basis for developing 'off-switch' tools for SpyCas9 to avoid unwanted genome
      edits within cells and tissues.

PMID- 28448068
TI  - Addressing reproducibility in single-laboratory phenotyping experiments.

PMID- 28448065
TI  - Construction of a map-based reference genome sequence for barley, Hordeum vulgare
      L.
AB  - Barley (Hordeum vulgare L.) is a cereal grass mainly used as animal fodder and
      raw material for the malting industry. The map-based reference genome sequence of
      barley cv. 'Morex' was constructed by the International Barley Genome Sequencing
      Consortium (IBSC) using hierarchical shotgun sequencing. Here, we report the
      experimental and computational procedures to (i) sequence and assemble more than
      80,000 bacterial artificial chromosome (BAC) clones along the minimum tiling path
      of a genome-wide physical map, (ii) find and validate overlaps between adjacent
      BACs, (iii) construct 4,265 non-redundant sequence scaffolds representing
      clusters of overlapping BACs, and (iv) order and orient these BAC clusters along
      the seven barley chromosomes using positional information provided by dense
      genetic maps, an optical map and chromosome conformation capture sequencing (Hi
      C). Integrative access to these sequence and mapping resources is provided by the
      barley genome explorer (BARLEX).

PMID- 28448069
TI  - Systems biology guided by XCMS Online metabolomics.

PMID- 28448070
TI  - How to deduplicate PCR.

PMID- 28448071
TI  - Azathioprine Maintenance Therapy to Prevent Relapses in Autoimmune Pancreatitis.
AB  - OBJECTIVES: Steroids are used to induce remission in autoimmune pancreatitis
      (AIP). Low-dosage steroid therapy or immunosuppressant (IMs) has been proposed as
      maintenance therapy to prevent AIP relapse. Few and conflicting data have been
      published on the efficacy of azathioprine (AZA) in preventing AIP relapse. The
      aim of this study was to evaluate the indication and efficacy of AZA as
      maintenance therapy to prevent disease relapse in AIP. METHODS: Patients
      suffering from AIP diagnosed according to the ICDC in type 1, type 2, and not
      otherwise specified (NOS) were divided in those treated with AZA (AZA+ group) as
      maintenance therapy and not treated with maintenance therapy (AZA- group).
      Exclusion criteria were: previous pancreatic surgery, other autoimmune diseases
      as indication for AZA treatment, and use of IMs different from AZA. Drug safety,
      clinical and instrumental outcome of AZA+ patients were evaluated. RESULTS: A
      total of 23 patients (18 Males and 5 Females, mean age 54+/-11 years) in AZA+
      group and 97 (58 Males and 39 Females, mean age 45+/-18 years) in AZA- group were
      compared. In AZA+ group, patients were significantly older (P=0.043), type 1 AIP
      was more frequently diagnosed (87 vs. 51%, P=0.006), sIgG4 higher (758+/-625 vs.
      311+/-409 mg/dl, P<0.001), other organ involvement (OOI) more frequently observed
      (83 vs. 48%, P=0.002), with higher frequency of relapse before AZA treatment (78
      vs. 14%, P<0.001). Three patients in AZA+ group required drug discontinuation
      because of adverse events. Twenty patients were therefore evaluated for outcome.
      Six out of 20 patients (30%) relapsed after 24+/-15 months (5 in pancreas and 1
      on biliary tract). They were retreated with steroids and continued AZA. Two out
      of 6 patients (33%) had a second relapse,after respectively 11 months (in
      pancreas and kidney) and 22 months (in kidney). CONCLUSIONS: AZA is an effective
      and safe treatment to prevent AIP relapses.

PMID- 28448072
TI  - Evaluation of PTGS2 Expression, PIK3CA Mutation, Aspirin Use and Colon Cancer
      Survival in a Population-Based Cohort Study.
AB  - OBJECTIVES: The association between aspirin use and improved survival after
      colorectal cancer diagnosis may be more pronounced in tumors that have PIK3CA
      mutations or high PTGS2 expression. However, the evidence of a difference in
      association by biomarker status lacks consistency. In this population-based colon
      cancer cohort study the interaction between these biomarkers, aspirin use, and
      survival was assessed. METHODS: The cohort consisted of 740 stage II and III
      colon cancer patients diagnosed between 2004 and 2008. Aspirin use was determined
      through clinical note review. Tissue blocks were retrieved to determine
      immunohistochemical assessment of PTGS2 expression and the presence of PIK3CA
      mutations. Cox proportional hazards models were used to calculate hazard ratios
      (HR) and 95% confidence intervals (CI) for colorectal cancer-specific and overall
      survival. RESULTS: In this cohort aspirin use was associated with a 31%
      improvement in cancer-specific survival compared to non-use (adjusted HR=0.69,
      95% CI 0.47-0.98). This effect was more pronounced in tumors with high PTGS2
      expression (PTGS2-high adjusted HR=0.55, 95% CI 0.32-0.96) compared to those with
      low PTGS2 expression (PTGS2-low adjusted HR=1.19, 95% CI 0.68-2.07, P for
      interaction=0.09). The aspirin by PTGS2 interaction was significant for overall
      survival (PTGS2-high adjusted HR=0.64, 95% CI 0.42-0.98 vs. PTGS2-low adjusted
      HR=1.28, 95% CI 0.80-2.03, P for interaction=0.04). However, no interaction was
      observed between aspirin use and PIK3CA mutation status for colorectal cancer
      specific or overall survival. CONCLUSIONS: Aspirin use was associated with
      improved survival outcomes in this population-based cohort of colon cancer
      patients. This association differed according to PTGS2 expression but not PIK3CA
      mutation status. Limiting adjuvant aspirin trials to PIK3CA-mutant colorectal
      cancer may be too restrictive.

PMID- 28448074
TI  - Simultaneous electrical recording of cardiac electrophysiology and contraction on
      chip.
AB  - Prevailing commercialized cardiac platforms for in vitro drug development utilize
      planar microelectrode arrays to map action potentials, or impedance sensing to
      record contraction in real time, but cannot record both functions on the same
      chip with high spatial resolution. Here we report a novel cardiac platform that
      can record cardiac tissue adhesion, electrophysiology, and contractility on the
      same chip. The platform integrates two independent yet interpenetrating sensor
      arrays: a microelectrode array for field potential readouts and an interdigitated
      electrode array for impedance readouts. Together, these arrays provide real-time,
      non-invasive data acquisition of both cardiac electrophysiology and contractility
      under physiological conditions and under drug stimuli. Human induced pluripotent
      stem cell-derived cardiomyocytes were cultured as a model system, and used to
      validate the platform with an excitation-contraction decoupling chemical.
      Preliminary data using the platform to investigate the effect of the drug
      norepinephrine are combined with computational efforts. This platform provides a
      quantitative and predictive assay system that can potentially be used for
      comprehensive assessment of cardiac toxicity earlier in the drug discovery
      process.

PMID- 28448075
TI  - Visible-light-induced and iron-catalyzed methylation of N-arylacrylamides with
      dimethyl sulphoxide: a convenient access to 3-ethyl-3-methyl oxindoles.
AB  - A visible-light-induced and iron-catalyzed methylation of arylacrylamides by
      dimethyl sulphoxide (DMSO) is achieved, leading to 3-ethyl-3-methyl indolin-2
      ones in high yields. This reaction tolerates a series of functional groups, such
      as methoxy, trifluoromethyl, cyano, nitro, acetyl and ethyloxy carbonyl groups.
      The visible-light promoted radical methylation and arylation of the alkenyl group
      are involved in this reaction.

PMID- 28448076
TI  - Tea Consumption and Health-Related Quality of Life in Older Adults.
AB  - BACKGROUND: Although tea consumption has been reported to have various health
      benefits in humans, its association with health-related quality of life (HRQOL)
      has not been investigated directly. We aimed to examine the relationship between
      tea consumption and HRQOL among older Chinese adults. METHODS: We analyzed
      community-based cross-sectional data of 5,557 older Chinese individuals aged 60
      years or older who participated in the Weitang Geriatric Diseases study.
      Information on tea consumption and HRQOL assessed by the European Quality of Life
      5 dimensions (EQ-5D) were collected by questionnaires. We estimated the
      relationship of tea consumption and the EQ-5D index score using linear regression
      models and the association between tea consumption and self-reported EQ-5D health
      problems using logistic regression models. RESULTS: The EQ-5D index score was
      higher for habitual tea drinkers than their counterparts. In multivariate linear
      analyses controlling for socio-demographic conditions, health conditions, and
      lifestyle habits, the differences in ED-5D index score between individuals with
      and without tea drinking habits was 0.012 (95% confidence interval, 0.006-0.017).
      In multivariate logistic analyses, habitual tea drinking was inversely associated
      with reporting of problems in EQ-5D dimensions mobility (odds ration [OR], 0.44;
      95% CI: 0.23-0.84); pain/discomfort (OR, 0.74; 95% CI: 0.61-0.90); and
      anxiety/depression (OR, 0.60; 95% CI: 0.38-0.97). These associations were more
      evident for black or oolong tea than green tea. CONCLUSION: Habitual tea
      consumption was associated with better HRQOL in older adults.

PMID- 28448077
TI  - Construct Validation of the Dietary Inflammatory Index among African Americans.
AB  - OBJECTIVE: Chronic inflammation is linked to many chronic conditions. One of the
      strongest modulators of chronic inflammation is diet. The Dietary Inflammatory
      Index (DII) measures dietary inflammatory potential and has been validated
      previously, but not among African Americans (AAs). DESIGN: Cross-sectional
      analysis using baseline data from the Healthy Eating and Active Living in the
      Spirit (HEALS) intervention study. SETTING: Baseline data collection occurred
      between 2009 and 2012 in or near Columbia, SC. PARTICIPANTS: African-American
      churchgoers. MEASUREMENTS: Baseline data collection included c-reactive protein
      (CRP) and interleukin-6 from blood draws, anthropometric measures, and numerous
      questionnaires. The questionnaires included a food frequency questionnaire which
      was used for DII calculation. The main analyses were performed using quantile
      regression. RESULTS: Subjects in the highest DII quartile (i.e., more pro
      inflammatory) were younger, more likely to be married, and had less education and
      greater BMI. Individuals in DII quartile 4 had statistically significantly
      greater CRP at the 75th and 90th percentiles of CRP versus those in quartile 1
      (i.e., more anti-inflammatory). CONCLUSION: Construct validation provides support
      for using the DII in research among AA populations. Future research should
      explore avenues to promote more anti-inflammatory diets, with use of the DII,
      among AA populations to reduce risk of chronic disease.

PMID- 28448078
TI  - Food Consumption and Nutrient Intake in Relation to Denture Use in 55- to 84-Year
      Old Men and Women -Results of a Population Based Survey.
AB  - OBJECTIVE: To study differences in consumption of foods and intake of nutrients
      attributable to denture status. DESIGN, SETTING AND PARTICIPANTS: Data from a
      cross-sectional, nationally representative Health 2000 Survey, subjects aged 55
      84 years (n=2,241). MEASUREMENTS: Denture status (edentulous with full dentures,
      own dentition with removable dentures, own dentition with no removable dentures)
      was used as an explanatory variable. The consumption of foods and intake of
      nutrients was used as an outcome variable and was measured using a validated Food
      Frequency Questionnaire. RESULTS: Denture status associated with food choices.
      Full denture wearers consumed less vegetables (p = 0.013 among men and p = 0.001
      among women) and fruits (p = 0.001 among women), more sugary products (p = 0.012
      among men and p = 0.008 among women), and their balance in fatty acids was less
      favourable than among dentate participants. Among dentate participants, the
      differences between the two groups were small and statistically significant
      differences were seen mostly in women. CONCLUSIONS: Wearing full dentures appears
      to be associated with unhealthier food choices, lower consumption of some
      foodstuffs and lower intake of certain nutrients when compared to the food
      choices of dentate persons.

PMID- 28448079
TI  - Relationship between Breakfast Skipping and Obesity among Elderly: Cross
      Sectional Analysis of the HEIJO-KYO Study.
AB  - OBJECTIVE: Breakfast skipping is reported to be associated with obesity in
      children and younger populations; however, few studies report the association
      among elderly. The purpose of this study was to investigate the relationships
      between breakfast skipping and obesity prevalence among elderly. DESIGN: Cross
      sectional study. SETTING: Community-dwelling elderly in Nara, Japan.
      PARTICIPANTS: 1052 elderly participants (mean age: 71.6 years). MEASUREMENTS:
      Obesity and breakfast skipping were defined as body mass index of >=25 kg/m2 and
      skipping breakfast one or more times per week, respectively. RESULTS: Two hundred
      and seventy-two participants (25.9%) were classified as obese and forty-one
      (3.9%) were as breakfast skippers. Obesity prevalence was significantly higher in
      breakfast skippers than in breakfast eaters (43.9% vs. 25.1%, P = 0.007). In
      multivariable logistic regression analysis adjusted for potential confounders
      (age, sex and alcohol consumption), breakfast skippers showed significantly
      higher odds ratio (OR) for obesity than breakfast eaters (OR, 2.23; 95%
      confidence interval, 1.17-4.27; P = 0.015), which continued to be significant
      after further adjustment for socioeconomic status. In addition, breakfast
      skippers showed significantly lower daily potassium (P <0.001) and dietary fibre
      intakes (P = 0.001) and lower subjective physical activity (P = 0.035) than
      breakfast eaters. CONCLUSIONS: Breakfast skipping was significantly associated
      with obesity among elderly. Poor diet quality and physical inactivity may be
      potential intermediators underlying the association between breakfast skipping
      and obesity.

PMID- 28448080
TI  - Adherence to the Mediterranean Diet and All-Cause Mortality Risk in an Elderly
      Italian Population: Data from the ILSA Study.
AB  - OBJECTIVE: The aim of this study was to evaluate adherence to the Mediterranean
      Diet (MD) and its association with all-cause mortality in an elderly Italian
      population. DESIGN: Data analysis of a longitudinal study of a representative,
      age stratified, population sample. SETTING: Study data is based upon the Italian
      Longitudinal Study on Aging (ILSA) a prospective, community-based cohort study.
      The baseline evaluation was carried out in 1992 and the follow-up in 1996 and
      2000. PARTICIPANT: Participant food intake assessment was available at baseline
      for 4,232 subjects; information on survival was available for 2,665 at the 2000
      follow-up. MEASUREMENTS: Adherence to the MD was evaluated with an a priori score
      based on the Mediterranean pyramid components. Cox proportional hazard models
      were used to assess the relationship between the MD score and all-cause
      mortality. Six hundred and sixty five subjects had died at the second follow-up
      (identified up to the first and second follow-up together; mean follow-up: 7.1+/
      2.6 years). RESULTS: At the 2000 follow-up, adjusting for other confounding
      factors, participants with a high adherence to MD (highest tertile of the MD
      score distribution) had an all-cause mortality risk that was of 34% lower with
      respect to the subjects with low adherence (Hazard Ratio=0.66; 95% CI: 0.49-0.90;
      p=0.0144). CONCLUSION: According to study results, a higher adherence to the MD
      was associated with a low all-cause mortality risk in an elderly Italian
      population.

PMID- 28448081
TI  - Association between Satisfaction with State of Health and Meals, Physical
      Condition and Food Diversity, Health Behavior, and Perceptions of Shopping
      Difficulty among Older People Living Alone in Japan.
AB  - OBJECTIVE: This study aimed to examine perceptions of shopping difficulty, and
      the relationships with satisfaction with state of health and meals, physical
      condition, food diversity and health behavior in older people living alone in
      Japan. DESIGN: A cross-sectional, multilevel survey was designed. The
      questionnaire was distributed by mail and self-completed by participants.
      SETTING: The sample was drawn from seven towns and cities across Japan.
      PARTICIPANTS: A geographic information system was used to select the sample of
      older people living alone, by proximity to a supermarket. In total, 2,346 older
      people (827 men and 1,519 women) completed the questionnaire. MEASUREMENTS: The
      dependent variable was whether shopping was easy or difficult. A logistic
      regression analysis was performed, adjusting for age, socioeconomic status and
      proximity of residence to a supermarket using stepwise variable analyses.
      RESULTS: The response rate was 67.8%. Overall, 14.5% of men and 21.7% of women
      considered shopping difficult. The stepwise logistic analysis showed that the
      factors most strongly related to shopping difficulty were a subjective feeling of
      poor health (men: OR = 3.01, women: OR = 2.16) and lack of satisfaction with
      meals (men: OR = 2.82, women: OR = 3.69). Other related physical condition and
      dietary factors were requiring nursing care (men: OR = 3.69, women: OR = 1.54), a
      high level of frailty, measured using the frailty index score (women: OR = 0.36)
      and low food diversity score (men: OR = 1.84, women: OR = 1.36). CONCLUSION: The
      study found that older people's assessment of their shopping difficulty was
      related to satisfaction aspects, including a subjective feeling of poor health,
      and lack of satisfaction with meals, as well as physical condition. These have a
      greater influence on shopping difficulty than income in both sexes, and proximity
      to a supermarket in women.

PMID- 28448082
TI  - Effects of Gender and Age on Immune Responses of Human Peripheral Blood
      Mononuclear Cells to Probiotics: A Large Scale Pilot Study.
AB  - BACKGROUND: Despite the widely accepted concept that probiotics confer
      miscellaneous benefits to hosts, the controversies surrounding these health
      promoting claims cannot be ignored. These controversies hinder development and
      innovation in this field. RESULTS: To clarify the effects of age and gender on
      probiotic-induced immune responses, we recruited 1613 Taiwanese individuals and
      calculated the ratio of IFN-gamma to IL-10 production after each individual's
      PBMCs were stimulated by six probiotic strains (L. paracasei BRAP01, L.
      acidophilus AD300, B. longum BA100, E. faecium BR0085, L. rhamnosus AD500 and L.
      reuteri BR101). Our results indicated that gender and age have only minor effects
      on the immune modulation of probiotics. Additionally, we showed that L. paracasei
      BRAP01 and L. acidophilus AD300 are the two dominant strains inducing IFN
      gamma/IL-10 production in Taiwanese individuals and that L. reuteri BR101 was the
      most effective stimulator of IL-10/IFN-gamma. Additionally, a significant inverse
      relationship between the ability of L. paracasei BRAP01 and L. rhamnosus AD500 to
      stimulate IFN-gamma/IL-10 or IL-10/IFN-gamma production was also observed.
      CONCLUSIONS: Our results indicated that age and gender have only minor effects on
      the immune modulation abilities of probiotics.

PMID- 28448083
TI  - Are Dietary Supplements and Nutraceuticals Effective for Musculoskeletal Health
      and Cognitive Function? A Scoping Review.
AB  - OBJECTIVE: The aim of our scoping review was to summarize the state of the art
      regarding micronutrients in order to identify which of them might effectively
      improve health status in the areas typically impaired in older people: bone,
      skeletal muscle, and cognitive function. DESIGN: Scoping review. METHODS: The
      Italian Study Group on Healthy Aging by Nutraceuticals and Dietary Supplements
      (HANDS) performed this scoping review, based on the following steps: doing a list
      of micronutrients related with musculoskeletal or cognitive functions, included
      in dietary supplements and nutraceuticals commercialized in Italy; planning a
      research on PubMed, according to an evidence-based approach, in order to the most
      relevant positive study for each micronutrient into each of the three areas
      involved (bone, skeletal muscle and cognitive function); identifying the
      micronutrients effective in maintaining or achieving an adequate health status in
      older people, specifying the effective and safe daily doses, according to the
      selected studies. RESULTS: In literature we found 12 relevant positive studies (1
      international society guidelines/recommendations, 1 systematic review, 7
      randomized controlled trials, and 3 prospective cohort studies). We showed that
      only 16 micronutrients resulted to have appropriate scientific evidences in terms
      of improving musculoskeletal health and/or cognitive function in older people:
      beta-alanine, calcium, creatine, fluorides, leucine, magnesium, omega-3 fatty
      acids, potassium, vitamin B6, vitamin B9, vitamin B12, vitamin C, vitamin D,
      vitamin E, vitamin K2, and zinc. CONCLUSION: This scoping review showed that
      selected micronutrients in adequate doses might have an ancillary role in
      musculoskeletal health and cognitive functions in older people.

PMID- 28448084
TI  - DNA Damage, Copper and Lead Associates with Cognitive Function among Older
      Adults.
AB  - BACKGROUND: A cross sectional study was conducted in a group of 317 subjects
      older than 60 in Malaysia, aimed to determine risk factors associated with
      cognitive impairment in older adults, focusing on trace elements and DNA damage.
      METHOD: Cognitive decline was determined by Montreal Cognitive Assessment (MoCA).
      Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were
      determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples
      were taken and analyzed using ICP-MS to determine trace element levels. RESULTS:
      A total of 62.1 % of subjects had cognitive impairment. Subjects with cognitive
      impairment had significantly higher levels of MDA and DNA damage as compared to
      the group with normal cognitive function; MDA (2.07 +/- 0.05 nmol/L vs 1.85 +/-
      0.06 nmol/L) (p<0.05) and DNA damage (% Tail Density, 14.52 +/- 0.32 vs 10.31 +/-
      0.42; Tail Moment, 1.79 +/- 0.06 vs 1.28 +/- 0.06) (p<0.05 for all parameters).
      However, the level of SOD among subjects with cognitive impairment (6.67 +/- 0.33
      u.e/min/mg protein) was lower than the level among those with normal cognitive
      functions (11.36 +/- 0.65 u.e/min/mg protein) (p<0.05). Multiple logistic
      regression revealed the predictors for cognitive impairment among the subjects
      were DNA damage (Adjusted odd ratio [OR], 1.37; 95% confidence interval [CI],
      1.18-1.59), level of trace elements in toenails namely, lead (OR, 2.471; CI,
      1.535-3.980) and copper (OR, 1.275; CI, 1.047-1.552) (p<0.05). CONCLUSION: High
      levels of lead and copper can lead to increase in oxidative stress levels and are
      associated with DNA damage that eventually could be associated with cognitive
      decline.

PMID- 28448085
TI  - Obesity and Cognitive Decline in Adults: Effect of Methodological Choices and
      Confounding by Age in a Longitudinal Study.
AB  - BACKGROUND AND OBJECTIVES: Obesity has been associated with increased risk of
      cognitive impairment or dementia, but recent findings are contradictory, possibly
      due to methodological differences. The present study tries to clarify these
      inconsistencies by following the cognitive trajectories of individuals with
      obesity over 12 years and studying the effect of obesity status (obesity at
      baseline versus incident obesity at follow-up), chronicity, definition, potential
      confounding (e.g. age, cardiovascular factors), and non-linear associations.
      DESIGN: Longitudinal study with 12 years follow-up. SETTING: Community based.
      PARTICIPANTS: 1,807 cognitively healthy individuals (aged 24-83) from the
      Maastricht Aging Study (1992-2004). MEASUREMENTS: Memory, executive function and
      processing speed were assessed at baseline and at 6- and 12-year follow-up.
      Obesity was defined as having a body mass index (BMI) of >= 30.0 kg/m2 or waist
      circumference (WC) of > 102 cm for men and > 88 cm for women. RESULTS: At
      baseline, 545 persons were obese (BMI: 329 (18%); WC: 494 (27%); both: 278 (15%).
      They showed faster decline in memory, executive function, and processing speed.
      Chronic obese showed less widespread impairment than those who regained normal
      weight. Associations across cognitive domains were weaker for obesity defined by
      BMI than for WC. At follow-up, 190 developed obesity, and they performed worse on
      executive function at baseline, but showed less decline compared with
      participants with normal weight. Yet, age-stratification and post-hoc analyses
      showed that most of these associations were confounded by age. CONCLUSIONS: This
      study shows that the association between obesity and cognitive decline was
      confounded by the effect of age on rate of decline. Future studies should take
      this into account.

PMID- 28448086
TI  - Effects of Running Wheel Activity and Dietary HMB and beta-alanine Co
      Supplementation on Muscle Quality in Aged Male Rats.
AB  - OBJECTIVE: Loss of skeletal muscle function is linked to increased risk for loss
      of health and independence in older adults. Dietary interventions that can
      enhance aging muscle function, alone or in combination with exercise, may offer
      an effective way to reduce these risks. The goal of this study was to evaluate
      the muscular effects of beta-hydroxy-beta-methylbutyrate (HMB) and beta-alanine
      (beta-Ala) co-supplementation in aged Sprague-Dawley rats with voluntary access
      to running wheels (RW). METHODS: Aged (20 months) rats were housed with ad
      libitum access to RW while on a purified diet for 4 weeks, then balanced for RW
      activity and assigned to either a control or an experimental diet (control + HMB
      and beta-Ala) for the next 4 weeks (n = 10/group). At the end of the study, we
      assessed muscle size, in situ force and fatigability in the medial gastrocnemius
      muscles, as well as an array of protein markers related to various age- and
      activity-responsive signaling pathways. RESULTS: Dietary HMB+beta-Ala did not
      improve muscle force or fatigue resistance, but a trend for increased muscle
      cross-sectional area (CSA) was observed (P = 0.077). As a result, rats on the
      experimental diet exhibited reduced muscle quality (force/CSA; P = 0.032).
      Dietary HMB+beta-Ala reduced both the abundance of PGC1-alpha (P = 0.050) and the
      ratio of the lipidated to non-lipidated forms of microtubule-associated protein 1
      light chain 3 beta (P = 0.004), markers of mitochondrial biogenesis and
      autophagy, respectively. Some alterations in myostatin signaling also occurred in
      the dietary HMB+beta-Ala group. There was an unexpected difference (P = 0.046) in
      RW activity, which increased throughout the study in the animals on the control
      diet, but not in animals on the experimental diet. CONCLUSIONS: These data
      suggest that the short-term addition of dietary HMB+beta-Ala to modest physical
      activity provided little enhancement of muscle function in this model of
      uncomplicated aging.

PMID- 28448087
TI  - Effect of a Mediterranean Type Diet on Inflammatory and Cartilage Degradation
      Biomarkers in Patients with Osteoarthritis.
AB  - OBJECTIVES: To investigate the effects of a Mediterranean type diet on patients
      with osteoarthritis (OA). PARTICIPANTS: Ninety-nine volunteers with OA (aged 31 -
      90 years) completed the study (83% female). SETTING: Southeast of England, UK.
      DESIGN: Participants were randomly allocated to the dietary intervention (DIET, n
      = 50) or control (CON, n = 49). The DIET group were asked to follow a
      Mediterranean type diet for 16 weeks whereas the CON group were asked to follow
      their normal diet. MEASUREMENTS: All participants completed an Arthritis Impact
      Measurement Scale (AIMS2) pre-, mid- and post- study period. A subset of
      participants attended a clinic at the start and end of the study for assessment
      of joint range of motion, ROM (DIET = 33, CON = 28), and to provide blood samples
      (DIET = 29, CON = 25) for biomarker analysis (including serum cartilage
      oligomeric matrix protein (sCOMP) (a marker of cartilage degradation) and a panel
      of other relevant biomarkers including pro- and anti-inflammatory cytokines).
      RESULTS: There were no differences between groups in the response of any AIMS2
      components and most biomarkers (p > 0.05), except the pro-inflammatory cytokine
      IL-1alpha, which decreased in the DIET group (~47%, p = 0.010). sCOMP decreased
      in the DIET group by 1 U/L (~8%, p = 0.014). There was a significant improvement
      in knee flexion and hip rotation ROM in the DIET group (p < 0.05). CONCLUSIONS:
      The average reduction in sCOMP in the DIET group (1 U/L) represents a meaningful
      change, but the longer term effects require further study.

PMID- 28448088
TI  - Individually Tailored Dietary Counseling among Old Home Care Clients - Effects on
      Nutritional Status.
AB  - OBJECTIVE: To evaluate the effect of individually tailored dietary counseling on
      nutritional status among home care clients aged 75 years or older. DESIGN: Non
      randomised controlled study. SETTING AND PARTICIPANTS: The study sample consisted
      of 224 home care clients (>= 75 years) (intervention group, n = 127; control
      group, n = 100) who were at protein-energy malnutrition (PEM) or risk of PEM (MNA
      score <24 and plasma albumin <35 g/L). INTERVENTION: Individually tailored
      dietary counseling; the persons were instructed to increase their food intake
      with energy-dense food items, the number of meals they ate and their consumption
      of energy-, protein- and nutrient-rich snacks for six months. MEASUREMENTS: The
      Mini Nutritional Assessment (MNA), Body Mass Index (BMI) and plasma albumin were
      used to determine nutritional status at the baseline and after the six-month
      intervention. RESULTS: The mean age of the home care clients was 84.3 (SD 5.5) in
      the intervention group and 84.4 (SD 5.3) in the control group, and 70 percent
      were women in both groups. After the six-month nutritional intervention, the MNA
      score increased 2.3 points and plasma albumin 1.6 g/L in the intervention group,
      against MNA score decreased -0.2 points and plasma albumin -0.1 g/L in the
      control group. CONCLUSIONS: Individually tailored dietary counseling may improve
      nutritional status among older home care clients.

PMID- 28448089
TI  - Bone Degeneration and Its Recovery in SMP30/GNL-Knockout Mice.
AB  - Senescence marker protein-30 (SMP30) decreases androgen-independently with aging
      and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in
      vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL
      knockout (KO) mice with deficiency in vitamin C synthesis were investigated to
      reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone
      formation. Mineral content (BMC) and mineral density (BMD) of the mandible and
      femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without
      vitamin C supplementation were measured by dual-energy X-ray absorptiometry. Body
      and bone weight of both age groups decreased and became significantly lower than
      those of wild-type mice. The bones of SMP30/GNL KO mice were rough and porous,
      with BMC and BMD significantly below wild-type. Oral supplementation with vitamin
      C eliminated differences in body weight, bone weight, BMC, and BMD between
      SMP30/GNL KO and wild-type mice at each age. These results indicate that bone
      degeneration in SMP30/GNL KO mice was caused by lack of vitamin C, and that this
      mouse strain is an appropriate model for bone metabolism in humans, which have no
      ability to synthesize vitamin C.

PMID- 28448090
TI  - Is It Possible Using Handgrip Strength Instead of Body Mass Index in MNA-SF Test
      to Assess the Nutritional Status of Geriatric Patients?
AB  - INTRODUCTION: In Mini-Nutritional Assessment-Short Form (MNA-SF) test, a
      practical and reliable alternative parameter is still necessary for patients with
      difficult body mass index evaluation. We aimed to show whether or not handgrip
      strength may be used instead of body mass index (BMI) in MNA-SF test. MATERIALS
      AND METHODS: MNA-SF test scores, calf circumferences (CC), handgrip strength
      (HGS), and BMI of 191 patients were evaluated. The first one of calculated MNA-SF
      tests was with BMI, the second one with CC, and the last one with HGS. Zero point
      was given if CC was <31 cm and 3 points were given if CC was >=31 cm. Zero, 1, 2,
      and 3 points were given if the loss of HGS when compared to expected HGS were
      >=%60, from >=%30 to <%60, from >=%10 to <%30, and <%10 or greater than expected
      HGS, respectively. MNA-SF scores and nutritional status according to these three
      measures were compared. RESULTS: Mean age and median MNA-SF scores of the
      patients were 75+/-7.6 years and 12 points (min-max: 0-14) respectively. There
      were strongly positive correlations between MNA-SF scores with BMI and CC, with
      BMI and HGS, and with CC and HGS (r=0.938 p<0.001, r=0.938 p<0.001, r=0.914
      p<0.001, respectively). Substantial agreement in nutritional status of the
      patients were seen between MNA-SF groups with BMI and CC, with CC and HGS, and
      with BMI and HGS (kappa: 0.795 p<0.001, kappa: 0.709 p<0.001, and kappa: 0.760
      p<0.001, respectively). CONCLUSIONS: HGS might be considered instead of BMI in
      MNA-SF test to assess nutritional status of geriatric patients.

PMID- 28448091
TI  - Association between Physical Frailty and Quality of Life in a Representative
      Sample of Community-Dwelling Swiss Older People.
AB  - OBJECTIVE: Though the association between physical frailty and health is well
      established, little is known about its association with other domains of quality
      of life (QoL). This study investigated the association between physical frailty
      and multiple domains of QoL in community-dwelling older people. DESIGN: Cross
      sectional study. SETTING AND PARTICIPANTS: Data of the 2011 annual assessment of
      927 older people (age 73-77 years) from the Lc65+ cohort study were used.
      MEASUREMENTS: Physical frailty was assessed by Fried's five criteria:
      'shrinking'; 'weakness'; 'poor endurance, exhaustion'; 'slowness'; and 'low
      activity'. QoL was assessed using 28 items yielding a QoL score and seven domain
      specific QoL subscores (Feeling of safety; Health and mobility; Autonomy; Close
      entourage; Material resources; Esteem and recognition; and Social and cultural
      life). Low QoL (QoL score or QoL subscores in the lowest quintile) was used as
      dependent variable in logistic regression analyses adjusted for age and sex
      (model 1), and additionally for socioeconomic (model 2) and health (model 3)
      covariates. RESULTS: Physical frailty was associated with a low QoL score, as
      well as decreased QoL subscores in all seven specific domains, even after
      adjusting for socio-economic covariates. However, when performing additional
      adjustment for health covariates, only the domain Health and mobility remained
      significantly associated with physical frailty. Among each specific Fried's
      criteria, 'slowness' had the strongest association with a low QoL score.
      CONCLUSION: Physical frailty is associated with all QoL domains, but these
      associations are largely explained by poor health characteristics. Longitudinal
      studies are needed to better understand temporal relationships between physical
      frailty, health and QoL.

PMID- 28448092
TI  - Handgrip Strength Predicts Longitudinal Changes in Clock Drawing Test
      Performance. An Observational Study in a Sample of Older Non-Demented Adults.
AB  - OBJECTIVE: Impairment of physical performance might identify older people at
      higher risk of dementia over time. The present study evaluated handgrip strength
      as independent predictor of cognitive decline. DESIGN: Observational,
      prospective. Follow-up duration: 11.2 +/- 0.8 months. SETTING AND PARTICIPANTS:
      Geriatric outpatients center. 104 consecutive stroke- and dementia-free older
      adults (44% men, ages 80.2 +/- 5.4 years). METHODS: The Clinical Dementia Rating
      scale and the Clock Drawing Test (CDT) were administered. Handgrip strength was
      assessed using a Jamar hand dynamometer. Brain magnetic resonance imaging studies
      at 1.5 T were performed. White matter damage was expressed as severity of white
      matter hyperintensities (WMHs). Longitudinal changes in cognitive function were
      expressed as 1-year decline in CDT performance. RESULTS: A robust association was
      observed between baseline handgrip strength and 1-year cognitive decline after
      multiple adjustment. Of note, the strength of such association was only minimally
      attenuated after adjusting for deep WMHs extent (beta coefficient for handgrip
      strength = 0.183, SE= 0.038, p= 0.007, R2= 0.58). CONCLUSIONS: Handgrip strength
      predicted accelerated 1-year decline in cognitive function, assessed by CDT, in a
      sample of older adults. Future studies are needed to elucidate the causal
      mechanisms linking limitations in physical function with dementia risk.

PMID- 28448094
TI  - High Prevalence of Personality Disorders in Skin-restricted Lupus Patients.
AB  - Psychiatric and personality disorders have been extensively documented in
      patients with systemic lupus erythematosus (SLE). However, the prevalence of
      personality disorders in skin-restricted lupus (SRL) patients remains unknown.
      The aim of this study was to assess the prevalence of personality disorders in
      SRL outpatients and to examine the associated factors. We evaluated 60 SRL
      outpatients and 118 controls matched for sex, age and education level. On the
      basis of the Personality Diagnostic Questionnaire 4+, 38% of patients vs 20% of
      controls fulfilled the criteria for at least one personality disorder (OR 2.2
      [95% CI 1.01-4.6], p = 0.048). Only one patient with a personality disorder had
      specialised mental health care. Late lupus onset and more frequent past
      treatments by thalidomide were associated factors. This study evidences a high
      prevalence of personality disorders in SRL patients and shows that most SRL
      patients with personality disorder do not receive specialised mental health care.

PMID- 28448093
TI  - Overweight and Abdominal Obesity Association with All-Cause and Cardiovascular
      Mortality in the Elderly Aged 80 and Over: A Cohort Study.
AB  - OBJECTIVE: To evaluate the association between overweight and abdominal obesity
      with all-cause and cardiovascular mortality in the elderly aged 80 and over.
      DESIGN: A prospective cohort study. SETTING: A population-based study of
      community-dwelling very elderly adults in a city in southern Brazil.
      PARTICIPANTS: 236 very elderly adults, number that represents 85% of the
      population aged 80 and over living in the city in the period (mean age 83.4 +/-
      3.2). MEASUREMENTS: Overweight and abdominal obesity were assessed using
      recommended cut-off points for body mass index (BMI), waist circumference (WC),
      waist-hip ratio (WHR) and waist-height ratio (WHtR). The association between
      these anthropometric measurements and all-cause and cardiovascular mortality were
      independently estimated by Cox proportional hazards model. Kaplan-Meier was used
      to assess survival time. RESULTS: Increased WC (>80cm F and >94cm M) and WHtR
      (>0.53 F and >0.52 M) were associated with lower all-cause mortality, but only
      WHtR remained associated even after controlling for residual confounding (HR 0.55
      CI95% 0.36-0.84; p<0.001). Additionally increased WC was independently associated
      with lower mortality from cardiovascular diseases (HR 0.57 CI95% 0.34-0.95;
      p<0.030). BMI and WHR did not show significant independent association with
      mortality in the main analysis. CONCLUSION: Greater abdominal fat accumulation,
      as estimated by WC and WHtR, presented an association with lower allcause and
      cardiovascular mortality in the elderly aged 80 and over, but not by BMI and WHR.

PMID- 28448095
TI  - Skin Ultrastructural Findings in Acquired Generalized Hypohidrosis/Anhidrosis in
      a Patient with Subclinical Sjogren Syndrome.

PMID- 28448096
TI  - Sebaceous Carcinomas of the Skin: 24 Cases and a Literature Review.

PMID- 28448097
TI  - Sudden Genital Ulceration in a Young Man: A Quiz.

PMID- 28448099
TI  - No Viral Transcripts Associated with Folliculotropic Mycosis Fungoides Using a
      High Throughput Sequencing Approach.
AB  - is missing (Short communication).

PMID- 28448098
TI  - A Monocentric Retrospective Cohort of Patients with Severe Atopic Dermatitis
      Treated with Cyclosporine A in Daily Practice.

PMID- 28448100
TI  - Electrochemotherapy for Non-melanoma Skin Cancer in a Child with Xeroderma
      Pigmentosum.

PMID- 28448103
TI  - Corrigendum.

PMID- 28448101
TI  - Actinic Keratosis, a Chronic, Progressive Disease: Understanding Clinical Gaps to
      Optimise Patient Management.

PMID- 28448104
TI  - Corrigendum.

PMID- 28448105
TI  - Corrigendum.

PMID- 28448107
TI  - Challenges for Small Biopharmaceutical Companies.

PMID- 28448109
TI  - How Medicaid Enrollees Fare Compared with Privately Insured and Uninsured Adults:
      Findings from the Commonwealth Fund Biennial Health Insurance Survey, 2016.
AB  - ISSUE: The number of Americans insured by Medicaid has climbed to more than 70
      million, with an estimated 12 million gaining coverage under the Affordable Care
      Act's Medicaid expansion. Still, some policymakers have questioned whether
      Medicaid coverage actually improves access to care, quality of care, or financial
      protection. GOALS: To compare the experiences of working-age adults who were
      either: covered all year by private employer or individual insurance; covered by
      Medicaid for the full year; or uninsured for some time during the year. METHOD:
      Analysis of the Commonwealth Fund Biennial Health Insurance Survey, 2016.
      FINDINGS AND CONCLUSIONS: The level of access to health care that Medicaid
      coverage provides is comparable to that afforded by private insurance. Adults
      with Medicaid coverage reported better care experiences than those who had been
      uninsured during the year. Medicaid enrollees have fewer problems paying medical
      bills than either the privately insured or the uninsured.

PMID- 28448110
TI  - Heavy Metals Induce Decline of Derivatives of 5-Methycytosine in Both DNA and RNA
      of Stem Cells.
AB  - Toxic heavy metals have been considered to be harmful environmental
      contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and
      carcinogenicity are still not well elucidated. Previous reports showed exposures
      to toxic heavy metals can cause a change of DNA cytosine methylation (5
      methylcytosine, 5-mC). However, it is still not clear whether heavy metals have
      effects on the recently identified new epigenetic marks in both DNA and RNA,
      i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5
      carboxylcytosine (5-caC). Here, we established a chemical labeling strategy in
      combination with liquid chromatography-electrospray ionization-mass spectrometry
      (LC-ESI-MS/MS) analysis for highly sensitive detection of eight modified
      cytidines in DNA and RNA. The developed method allowed simultaneous detection of
      all eight modified cytidines with improved detection sensitivities of 128-443
      fold. Using this method, we demonstrated that the levels of 5-hmC, 5-foC, and 5
      caC significantly decreased in both the DNA and RNA of mouse embryonic stem (ES)
      cells while exposed to arsenic (As), cadmium (Cd), chromium (Cr), and antimony
      (Sb). In addition, we found that treatments by heavy metals induced a decrease of
      the activities of 10-11 translocation (Tet) proteins. Furthermore, we revealed
      that a content change of metabolites occurring in the tricarboxylic acid cycle
      may be responsible for the decline of the derivatives of 5-mC. Our study shed
      light on the epigenetic effects of heavy metals, especially for the induced
      decline of the derivatives of 5-mC in both DNA and RNA.

PMID- 28448111
TI  - Stepwise Deprotonation of Magnetite-Supported Gallic Acid Modulates Oxidation
      State and Adsorption-Assisted Translocation of Hexavalent Chromium.
AB  - Recently, a synergistic strategy involving reduction of carcinogenic Cr(VI) into
      less toxic Cr(III) followed by Cr(III) adsorption and subsequent separation by
      surface-engineered magnetite nanoparticles has emerged as a promising alternative
      to address the environmental hazards associated with Cr(VI)-contaminated water.
      Despite several previous attempts exploiting this synergy, modulating the
      oxidation state and translocation of Cr(VI) with high spatiotemporal precision
      remains a major challenge. Here, we report how Cr(VI) responds accordingly in a
      well-defined manner to deprotonation of gallic acid covalently immobilized on
      magnetite nanoparticles, which proceeds through a fixed spatial sequence of
      distinct stages. To the best of our knowledge, this proof-of-principle study, for
      the first time, demonstrates that accurate spatiotemporal control over the
      cascading reduction-adsorption process of Cr(VI) by magnetic adsorbents is
      feasible, which provides guidance for rational design of more exquisite,
      magnetite-supported surfaces, where a predictable, and hence controllable,
      synergy can manifest for Cr(VI) detoxification.

PMID- 28448112
TI  - Real-Time Imaging of 2D and 3D Temperature Distribution: Coating of Metal-Ion
      Intercalated Organic Layered Composites with Tunable Stimuli-Responsive
      Properties.
AB  - Organic layered materials have intercalation and dynamic properties. The dynamic
      properties are tuned by the intercalation of the guests. In general, however, it
      is not easy to achieve the homogeneous and thin coating of the layered materials
      on substrates with complex shapes because of the two-dimensional anisotropic
      structures. In the present work, the layered organic composites were
      homogeneously coated on a variety of substrates for application to practical
      devices. The metal-ion-intercalated layered polydiacetylene (PDA-Mn+) with
      tunable stimuli-responsive color-change properties was coated on substrates, such
      as paper and cotton consisting of cellulose fibers. The homogeneous and thin
      coating of the precursor monomer crystal was achieved on the substrates through
      the controlled crystal growth. The intercalation and topochemical polymerization
      generated PDA-Mn+ on the substrates. The PDA-Mn+-coated devices visualized
      temperature distribution of two-dimensional surface and three-dimensional space
      in real time.

PMID- 28448113
TI  - Solvent-Free Chemical Approach to Synthesize Various Morphological Co3O4 for CO
      Oxidation.
AB  - Co3O4 nanomaterials with diverse morphologies were usually synthesized in liquid
      phase accompanied by the template or surfactant under harsh conditions, which
      further restricted their practical application. Herein, we reported an extremely
      simple and practical solid-state chemical method to synthesize Co3O4-octahedrons,
      -plates, and -rods. Among these, the shape control of Co3O4-octahedrons and Co3O4
      plates involve variation of the amount of reactant, and the formation of Co3O4
      rods with {110} facet can be achieved by replacing the reactant. The formation of
      the Co3O4 nanomaterials with different morphologies originated from the different
      microenvironments of reaction and the structure of reactants. The catalytic
      activity of Co3O4 samples for CO oxidation was evaluated in normal feed gas. The
      as-prepared Co3O4-rods exposed {110} facet exhibited superior catalytic activity
      for CO oxidation, which can be attributed to more oxygen defects on Co3O4-rods
      surface. Additionally, Co3O4-rods exhibited excellent durablility (without
      pretreatment) in normal feed gas, even in the presence of moisture, comparable or
      better than that reported in the literature. The practical and environmental
      friendly solvent-free strategy provided a new promising route for large-scale
      preparation of (metal) oxide with remarkable CO oxidation performance for
      practical application.

PMID- 28448114
TI  - Comparison of Ag(In,Ga)Se2/Mo and Cu(In,Ga)Se2/Mo Interfaces in Solar Cells.
AB  - The structural and electrical properties of the junction at Ag(In,Ga)Se2AIGS/Mo,
      and Cu(In,Ga)Se2 CIGS/Mo layers were characterized. The region between the CIGS
      and Mo featured a MoSe2 layer with a layered hexagonal structure and thickness of
      10-15 nm. The c-axis of the MoSe2 was oriented perpendicular to the Mo layer, and
      the c -value was 12.6 A. However, no such layer was observed at the interface
      between AIGS and Mo. This result was also confirmed by energy-dispersive X-ray
      spectrometry and X-ray diffraction measurements of the MoSe2 layer. The CIGS/Mo
      with a MoSe2 layer formed an ohmic contact, while the AIGS/Mo without the MoSe2
      layer formed a Schottky contact. This Schottky contact showed a barrier height of
      0.8 +/- 0.02 eV, a nonideality factor of 1.5 +/- 0.1, and a series resistance of
      370 +/- 8 Omega. A schematic band diagram of the AIGS/Mo junction was constructed
      on the basis of the above results.

PMID- 28448115
TI  - High-Temperature Superconductivity in Boron-Doped Q-Carbon.
AB  - We report high-temperature superconductivity in B-doped amorphous quenched carbon
      (Q-carbon). This phase is formed after nanosecond laser melting of B-doped
      amorphous carbon films in a super-undercooled state and followed by rapid
      quenching. Magnetic susceptibility measurements show the characteristics of type
      II Bardeen-Cooper-Schrieffer superconductivity with a superconducting transition
      temperature (Tc) of 36.0 +/- 0.5 K for 17.0 +/- 1.0 atom % boron concentration.
      This value is significantly higher than the best experimentally reported Tc of 11
      K for crystalline B-doped diamond. We argue that the quenching from metallic
      carbon liquid leads to a stronger electron-phonon coupling due to close packing
      of carbon atoms with higher density of states at the Fermi level. With these
      results, we propose that the non-equilibrium undercooling-assisted synthesis
      method can be used to fabricate highly doped materials that provide greatly
      enhanced superconducting properties.

PMID- 28448116
TI  - Quantitative Examination of the Active Targeting Effect: The Key Factor for
      Maximal Tumor Accumulation and Retention of Short-Circulated Biopolymeric
      Nanocarriers.
AB  - Targeted and nontargeted biopolymeric nanoparticles with identical hydrodynamic
      sizes and surface charges were quantitatively examined in terms of the
      pharmacokinetic and biodistribution differences in detail. In adding cancer cell
      targeting folate molecules to the surface of the heparin nanocarriers, the amount
      of drug delivered to the tumor is doubled, and tumor growth inhibition is
      significantly enhanced. The folate-targeted heparin particles offered similar
      therapeutic potentials compared to their synthetic long-circulating analogues,
      thus presenting a viable alternative for drug-delivery vehicle construction using
      biological polymers, which are easier for the body to eliminate.

PMID- 28448117
TI  - Eliminating the Animal Species Constraints in Antibody Selection for Multicolor
      Immunoassays.
AB  - Molecular profiling on the single-cell level helps unveil the mystery of gene
      expression patterns in individual cells at subcellular resolution, enabling
      discovery of small but meaningful variations that are often overlooked at the
      population level. Similar to other immunoassays, the most common and economical
      protocols are developed by combining primary antibodies (1'Abs) and fluorophore
      labeled secondary antibodies (2'Abs). The selection of 1' and 2' Abs, however,
      has been limited by the availability of animal species, consequently resulting in
      low multiplexing capability. Here we report the development of preassembled Ab
      pairs using 1'Abs all from the same animal species. We show that multiple
      molecular targets can be simultaneously labeled without cross reactivity. This
      simple and general self-assembly technology eliminates the animal species
      constraints in multicolor immunoassays, offering exciting new opportunities for a
      wide range of biomedical and clinical applications.

PMID- 28448118
TI  - Diamide Inhibitors of the Bacillus subtilis N-Acetylglucosaminidase LytG That
      Exhibit Antibacterial Activity.
AB  - N-Acetylglucosaminidases (GlcNAcases) play an important role in the remodeling
      and recycling of bacterial peptidoglycan by degrading the polysaccharide
      backbone. Genetic deletions of autolysins can impair cell division and growth,
      suggesting an opportunity for using small molecule autolysin inhibitors both as
      tools for studying the chemical biology of autolysins and also as antibacterial
      agents. We report here the synthesis and evaluation of a panel of diamides that
      inhibit the growth of Bacillus subtilis. Two compounds, fgkc (21) and fgka (5),
      were found to be potent inhibitors (MIC 3.8 +/- 1.0 and 21.3 +/- 0.1 MUM,
      respectively). These compounds inhibit the B. subtilis family 73 glycosyl
      hydrolase LytG, an exo GlcNAcase. Phenotypic analysis of fgkc (21)-treated cells
      demonstrates a propensity for cells to form linked chains, suggesting impaired
      cell growth and division.

PMID- 28448119
TI  - Sulfur Nanodots Stitched in 2D "Bubble-Like" Interconnected Carbon Fabric as
      Reversibility-Enhanced Cathodes for Lithium-Sulfur Batteries.
AB  - The behavior of two-dimensional (2D) materials for energy storage systems relates
      to their morphology and physicochemical properties. Although various 2D materials
      can be found in different fields, the open access of these materials has greatly
      hampered their practical applications, such as in lithium-sulfur (Li-S)
      batteries, where the soluble intermediates should be controlled. Here, we have
      developed a facile approach to prepare 2D ultrathin interconnected carbon fabrics
      (ICFs) with "bubble-like" morphology and abundant mesopores using a "blowing
      bubble" method. Serving as independent meso-sized rooms, nanosulfur dots can be
      stitched in 2D "bubble-like" ICF, which afford a short electron-/ion-transfer
      path and thus is beneficial to high reversible capacity. Encapsulated with
      reduced graphene oxide, a binder-free/free-standing cathode was constructed for
      advanced Li-S batteries. In addition, the specific energy of a pouch Li-S battery
      with this interconnected cathode can be achieved to 1.55 Ah@315.98 Wh/kg at 0.1
      C. These results suggest that the design of "bubble-like" interconnected porous
      carbon fabrics and their integration with reduced graphene oxide provide a facile
      strategy to enhance the electrochemical activity of S and have the potential to
      be applied to other semiconductors or insulating materials for a wide range of
      applications.

PMID- 28448120
TI  - Structural Properties of Double-Walled Carbon Nanotubes Driven by Mechanical
      Interlayer Coupling.
AB  - Structural identification of double-walled carbon nanotubes (DWNTs) is presented
      through a robust procedure based on the latest generation of transmission
      electron microscope, making possible a statistical analysis based on numerous
      nano-objects. This approach reveals that inner and outer tubes of DWNTs are not
      randomly oriented, suggesting the existence of a mechanical coupling between the
      two concentric walls. With the support of atomic-scale modeling, we attribute it
      to the presence of incommensurate domains whose structures depend on the
      diameters and helicities of both tubes and where inner tubes try to achieve a
      local stacking orientation to reduce strain effects.

PMID- 28448122
TI  - Iodine-Pseudohalogen Ionic Liquid-Based Electrolytes for Quasi-Solid-State Dye
      Sensitized Solar Cells.
AB  - In the current work, novel symmetrically alkyl-substituted imidazolium-based
      ionic liquids have been synthesized featuring either iodide (I-) or selenocyanate
      (SeCN-) as counteranions. Physicochemical assays based on spectroscopy and
      electrochemistry techniques have been performed to identify the best ionic liquid
      for application as electrolytes in quasi-solid-state dye-sensitized solar cells
      (qssDSSC). The latter were mixed with additives such as 4-tert-butylpyridine
      (4tbpy) and guanidinium thiocyanate (GuSCN) to optimize electrode surface
      coverage, ionic diffusion, and dye regeneration. In addition, we demonstrate that
      electrolytes containing a mixture of I2 and (SeCN)2 enhance the open-circuit
      voltage of the final quasi-solid-state device by up to 70 mV. As such, iodine
      pseudohalogen electrolytes reveal in qssDSSCs a good balance between dye
      regeneration and hole transport and, in turn, enhance the overall solar energy
      conversion efficiency by 70% with respect to reference qssDSSCs with iodine-based
      electrolytes. Finally, devices with the iodine-pseudohalogen electrolyte show a
      1000 h stable efficiency of 7-8% under outdoor temperature operation conditions
      and 1 sun illumination.

PMID- 28448123
TI  - Enhancing the Domain Wall Conductivity in Lithium Niobate Single Crystals.
AB  - Domain walls (DWs) in ferroelectric/ferroic materials have been a central
      research focus for the last 50 years; DWs bear a multitude of extraordinary
      physical parameters within a unit-cell-sized lateral confinement. Especially, one
      outstanding feature has recently attracted a lot of attention for room
      temperature applications, which is the potential to use DWs as two-dimensional
      (2D) conducting channels that completely penetrate bulk compounds. Domain wall
      currents in lithium niobate (LNO) so far lie in the lower pA regime. In this
      work, we report on an easy-to-use and reliable protocol that allows enhancing
      domain wall conductivity (DWC) in single-crystalline LNO (sc-LNO) by 3 to 4
      orders of magnitude. sc-LNO thus has become one of the most prospective
      candidates to engineer DWC applications, notably for domain wall transport both
      with and without photoexcitation. DWs were investigated here for several days to
      weeks, both before and after DWC enhancement. 2D local-scale inspections were
      carried out using adequate local-probe techniques, i.e., piezoresponse force
      microscopy and conductive atomic force microscopy, while Cerenkov second-harmonic
      generation was applied for mapping the DW constitution in three-dimensional space
      across the full LNO single crystal. The comparison between these nano- and
      microscale inspections allows us to unambiguously correlate the DW inclination
      angle alpha close to the sample surface to the measured domain wall current
      distribution. Moreover, ohmic or diode-like electronic transport characteristics
      along such DWs can be readily interpreted when analyzing the DW inclination
      profile.

PMID- 28448121
TI  - HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication
      Competent and Multi-Drug-Resistant HIV in Human Cells.
AB  - The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical
      importance in the virus' life cycle, has been posited as a novel target for anti
      HIV drug development. We report the synthesis and evaluation of triazole
      containing compounds able to bind the FSS with high affinity and selectivity.
      Readily accessible synthetically, these compounds are less toxic than previously
      reported olefin congeners. We show for the first time that FSS-targeting
      compounds have antiviral activity against replication-competent HIV in human
      cells, including a highly cytopathic, multidrug-resistant strain. These results
      support the viability of the HIV-1 FSS RNA as a therapeutic target and more
      generally highlight opportunities for synthetic molecule-mediated interference
      with protein recoding in a wide range of organisms.

PMID- 28448124
TI  - Bioinspired Engineering of Poly(ethylene glycol) Hydrogels and Natural Protein
      Fibers for Layered Heart Valve Constructs.
AB  - Layered constructs from poly(ethylene glycol) (PEG) hydrogels and chicken
      eggshell membranes (ESMs) are fabricated, which can be further cross-linked by
      glutaraldehyde (GA) to form GA-PEG-ESM composites. Our results indicate that ESMs
      composed of protein fibrous networks show elastic moduli ~3.3-5.0 MPa and
      elongation percentages ~47-56%, close to human heart valve leaflets. Finite
      element simulations reveal obvious stress concentration on a partial number of
      fibers in the GA-cross-linked ESM (GA-ESM) samples, which can be alleviated by
      efficient stress distribution among multiple layers of ESMs embedded in PEG
      hydrogels. Moreover, the polymeric networks of PEG hydrogels can prevent mineral
      deposition and enzyme degradation of protein fibers from incorporated ESMs. The
      fibrous structures of ESMs retain in the GA-PEG-ESM samples after subcutaneous
      implantation for 4 weeks, while those from ESM and GA-ESM samples show early
      degradation to certain extent, suggesting the prevention of enzymatic degradation
      of protein fibers by the polymeric network of PEG hydrogels in vivo. Thus, these
      GA-PEG-ESM layered constructs show heterogenic structures and mechanical
      properties comparable to heart valve leaflets, as well as improved functions to
      prevent progressive calcification and enzymatic degeneration, which are likely
      used for artificial heart valves.

PMID- 28448125
TI  - Efficient Computation of Exchange Energy Density with Gaussian Basis Functions.
AB  - Density functional theory (DFT) is widely applied in chemistry and physics. Still
      it fails to correctly predict quantitatively or even qualitatively for systems
      with significant nondynamic correlation. Several DFT functionals were proposed in
      recent years to treat the nondynamic correlation, most of which added the exact
      exchange energy density as a new variable. This quantity, calculated as Hartree
      Fock (HF) exchange energy density, is the computational bottleneck for
      calculations with these new functionals. We present an implementation of an
      efficient seminumerical algorithm in this paper as a solution for this
      computational bottleneck. The method scales quadratically with respect to the
      molecular size and the basis set size. The scheme, exact for the purpose of
      computing the HF exchange energy density, is favored for medium-sized basis sets
      and can be competitive even for large basis sets with efficient grids when
      compared with our previous approximate resolution-of-identity scheme. It can also
      be used as a seminumerical integration scheme to compute the HF exchange energy
      and matrix on a standard atom-centered grid. Calculations on a series of alanine
      peptides show that for large basis sets the seminumerical scheme becomes
      competitive to the conventional analytical method and can be about six times
      faster for aug-cc-pvtz basis. The practicality of the algorithm is demonstrated
      through a local hybrid self-consistent calculation of the acenes-20 molecule.

PMID- 28448126
TI  - From Surprising Solvothermal Reaction to Uncommon Zinc(II)-Catalyzed Aromatic C-H
      Activation Reaction for Direct Nitroquinoline Synthesis.
AB  - In this work, we first found a surprising solvothermal reaction for direct
      dinitration of quinoline derivative. To explore the application in direct
      nitroquinoline synthesis, this reaction was subsequently modified as an
      equivalent reaction in a Schlenk tube. More significantly, after a constant
      attempt, nitrated derivative was obtained in optimized condition with a zinc(II)
      sulfate catalyst, where some substrates with strong electron-withdrawing group
      were first nitrated by a directly catalyzed condition. This new zinc(II)
      catalyzed aromatic C-H activation reaction is the first example of direct
      dinitration by a single catalyst, which will be a new facile and environmentally
      friendly strategy to access synthetically useful nitroquinoline derivative.

PMID- 28448127
TI  - Organo-Copper(II) Complexes as Products of Radical Atom Transfer.
AB  - Copper complexes bearing polyamine chelate ligands are among the most widely used
      and highly active catalysts for atom transfer radical polymerization (ATRP).
      Copper(I) complexes of these ligands (CuIL) react with an alkyl halide initiator
      (RX) in the atom transfer step to generate the higher oxidation state halido
      complex CuIILX and the radical R*. However, CuIL present in the reaction also has
      the potential to react with the liberated radicals to generate the organometallic
      species CuIILR (where R is formally a carbanion). The reversible association of
      radical and CuIL would facilitate the operation of an alternate, competitive
      controlled radical polymerization pathway known as organometallic-mediated
      radical polymerization (OMRP). Recently this possibility has been proposed to
      occur for a number of different copper catalysts under ATRP conditions, but
      unequivocal evidence of this organometallic adduct is lacking. Herein we provide
      direct observation of this species, including an optical spectrum for two of the
      most commonly used copper catalysts. Furthermore, using cyclic voltammetry
      coupled to simulations, we are able to determine each of the key thermodynamic
      and kinetic steps involved in both the atom transfer and radical transfer
      pathways to assess the impact of ligand, solvent, and initiator on these.

PMID- 28448129
TI  - Alkaline-Earth Derivatives of the Reactive [HB(C6F5)3]- Anion.
AB  - The beta-diketiminato magnesium amidoboranes [HC{(Me)CNDipp}2Mg(NMe2BH2NMe2.BH3)]
      and [HC{(t-Bu)CNDipp}2Mg(NMe2.BH3)] are readily converted to the corresponding
      derivatives of the [HB(C6F5)3]- anion by treatment with B(C6F5)3. The
      bis(borohydride) derivatives of the heaviest alkaline-earth elements, strontium
      and barium, may be similarly synthesized by reaction of strontium or barium
      dimethylamidoboranes and B(C6F5)3 and by metathesis reactions of either SrI2 or
      BaI2 and 2 molar equiv of K(HB(C6F5)3). The strontium and barium compounds have
      been fully characterized in solution and in the solid state as the respective
      tris(diethyl ether) and tetrakis(tetrahydrofuran) adducts. The magnesium compound
      [HC{(Me)CNDipp}2Mg(HB(C6F5)3)] has been applied to the catalytic hydroboration of
      i-PrN?C?N-i-Pr with HBpin. In contrast to carbodiimide hydroboration catalyzed by
      the corresponding beta-diketiminato magnesium hydride, which results in the
      exclusive production of the monoborylated amidine, use of the [HB(C6F5)3]-
      derivative provides the product of bis-borylation, the aminal H2C(N{Bpin}i-Pr)2,
      under mild conditions. A series of stoichiometric reactions highlight that, while
      this reactivity is likely to be primarily magnesium mediated, B(C6F5)3 plays a
      vital role both in the delivery of reactive hydride and through the Lewis acid
      activation of the heteroallene substrate and various reactive intermediates.

PMID- 28448128
TI  - Total Chemical Synthesis and Folding of All-l and All-d Variants of Oncogenic
      KRas(G12V).
AB  - The Ras proteins are essential GTPases involved in the regulation of cell
      proliferation and survival. Mutated oncogenic forms of Ras alter effector binding
      and innate GTPase activity, leading to deregulation of downstream signal
      transduction. Mutated forms of Ras are involved in approximately 30% of human
      cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long
      been considered "undruggable" due to its high affinity for GTP and its lack of
      hydrophobic binding pockets. Herein, we report a total chemical synthesis of all
      l- and all-d-amino acid biotinylated variants of oncogenic mutant KRas(G12V). The
      protein is synthesized using Fmoc-based solid-phase peptide synthesis and
      assembled using combined native chemical ligation and isonitrile-mediated
      activation strategies. We demonstrate that both KRas(G12V) enantiomers can
      successfully fold and bind nucleotide substrates and binding partners with
      observable enantiodiscrimination. By demonstrating the functional competency of a
      mirror-image form of KRas bound to its corresponding enantiomeric nucleotide
      triphosphate, this study sets the stage for further biochemical studies with this
      material. In particular, this protein will enable mirror-image yeast surface
      display experiments to identify all-d peptide ligands for oncogenic KRas,
      providing a useful tool in the search for new therapeutics against this
      challenging disease target.

PMID- 28448130
TI  - The Peculiar Role of the Au3 Unit in Aum Clusters: sigma-Aromaticity of the
      Au5Zn+ Ion.
AB  - The stability of small Aum (m = 4-7) clusters is investigated by analyzing their
      energetic, geometric, vibrational, magnetic, and electron density properties.
      Gold clusters can be constructed from stable cyclic 3-center-2-electron (3c-2e)
      Au3+ units (3-rings) with sigma-aromaticity. The stabilization requires a flow of
      negative charge from internal 3-rings with electron-deficient bonding to
      peripheral 3-ring units with stronger Au-Au bonds. The valence-isoelectronic
      clusters Au6 and Au5Zn+ have similar electronic properties: Au5Zn+ is a strongly
      sigma-aromatic molecule. An understanding of the structure of Aum clusters is
      obtained by deriving a Clar's Rule equivalent for polycyclic gold clusters: The
      structure with the larger number of rings with dominant 3c-2e character and a
      smaller degree of 3c-3e character occupies the global minimum of the Aum
      potential energy surface.

PMID- 28448131
TI  - Silk Resin with Hydrated Dual Chemical-Physical Cross-Links Achieves High
      Strength and Toughness.
AB  - Native silk fibers are known to demonstrate excellent mechanical properties such
      as high strength and ductility. However, regenerated silk material has not yet
      been used as a tough structural material in our everyday life. To recreate the
      mechanical properties with regenerated silk material, the network structure and
      hydration state of silk materials are studied and optimized in this study. This
      is the first to demonstrate the effect of chemical and physical cross-links in
      hydrated and dehydrated silk materials, namely, silk hydrogels and resins. Mild
      hydration conditions (relative humidity 20-60%) realizes tough and strong silk
      materials with chemical and physical cross-links. In the case of relatively high
      concentrations of silk molecules, contributions to the high strength and
      toughness of silk-based materials are considered to come not only from beta-sheet
      cross-links and chemical dityrosine links but also from entanglements and
      assembly via the hydrophobic interactions of silk molecules. In addition,
      dehydration treatment does not disturb the biodegradability of the silk resins in
      natural environments. Based on the overall results, the silk resins with
      controlled network structures and hydration state have successfully achieved the
      highest toughness possible for a bulk silk material while maintaining favorable
      biodegradability.

PMID- 28448132
TI  - Eu(III) Chiral Coordination Polymer with a Structural Transformation System.
AB  - A luminescent Eu(III) chiral coordination polymer with a structural
      transformation system, [Eu(hfa)3((R)-bidp)]n (hfa: haxafluoroacetylacetonato, (R)
      bidp: (R)-1,1'-binaphthyl-2,2'-bis(diphenylphosphinate), is reported. Single
      crystal X-ray analysis revealed a characteristic helical polymer structure of
      [Eu(hfa)3((R)-bidp)]n with hydrogen-fluorine/pi interactions. [Eu(hfa)3((R)
      bidp)]n shows high thermostability (decomposition temperature = 320  degrees C)
      and strong luminescence properties (the 4f-4f emission quantum yield = 76%) in
      the solid state due to its tight packing and asymmetric structure. [Eu(hfa)3((R)
      bidp)]n is also transformed from a polymer to monomer structure in liquid media.
      The chiroptical properties of the monomer form in liquid media were characterized
      by using circular dichroism and circularly polarized luminescence spectra. In
      this study, structural and photophysical properties of a luminescent Eu(III)
      chiral coordination polymer with a structural transformation system were
      demonstrated.

PMID- 28448133
TI  - Design of Novel Exendin-Based Dual Glucagon-like Peptide 1 (GLP-1)/Glucagon
      Receptor Agonists.
AB  - Dual activation of the glucagon-like peptide 1 (GLP-1) and glucagon receptor has
      the potential to lead to a novel therapy principle for the treatment of
      diabesity. Here, we report a series of novel peptides with dual activity on these
      receptors that were discovered by rational design. On the basis of sequence
      analysis and structure-based design, structural elements of glucagon were
      engineered into the selective GLP-1 receptor agonist exendin-4, resulting in
      hybrid peptides with potent dual GLP-1/glucagon receptor activity. Detailed
      structure-activity relationship data are shown. Further modifications with
      unnatural and modified amino acids resulted in novel metabolically stable
      peptides that demonstrated a significant dose-dependent decrease in blood glucose
      in chronic studies in diabetic db/db mice and reduced body weight in diet-induced
      obese (DIO) mice. Structural analysis by NMR spectroscopy confirmed that the
      peptides maintain an exendin-4-like structure with its characteristic tryptophan
      cage fold motif that is responsible for favorable chemical and physical
      stability.

PMID- 28448134
TI  - Total Mercury Released to the Environment by Human Activities.
AB  - We estimate that a cumulative total of 1540 (1060-2800) Gg (gigagrams, 109 grams
      or thousand tonnes) of mercury (Hg) have been released by human activities up to
      2010, 73% of which was released after 1850. Of this liberated Hg, 470 Gg were
      emitted directly into the atmosphere, and 74% of the air emissions were elemental
      Hg. Cumulatively, about 1070 Gg were released to land and water bodies. Though
      annual releases of Hg have been relatively stable since 1880 at 8 +/- 2 Gg,
      except for wartime, the distributions of those releases among source types, world
      regions, and environmental media have changed dramatically. Production of Hg
      accounts for 27% of cumulative Hg releases to the environment, followed by silver
      production (24%) and chemicals manufacturing (12%). North America (30%), Europe
      (27%), and Asia (16%) have experienced the largest releases. Biogeochemical
      modeling shows a 3.2-fold increase in the atmospheric burden relative to 1850 and
      a contemporary atmospheric reservoir of 4.57 Gg, both of which agree well with
      observational constraints. We find that approximately 40% (390 Gg) of the Hg
      discarded to land and water must be sequestered at contaminated sites to maintain
      consistency with recent declines in atmospheric Hg concentrations.

PMID- 28448135
TI  - Total Synthesis of (+/-)-Lycojaponicumin D and Lycodoline-Type Lycopodium
      Alkaloids.
AB  - Lycopodium alkaloids with structural diversity and biological significance have
      been stimulating an increasing interest in the synthetic and medicinal
      communities, in which inspiration and exploration of their related biogenetic
      relationship generally constitute one of the major concerns. Driven by the
      plausible biogenetic entry to lycojaponicumin D as the first member of Lycopodium
      alkaloids having a structurally unusual C3-C13-linked scaffold, a new connection
      with lycodoline has been proposed and discovered on the basis of the design of an
      unprecedented bioinspired tandem fragmentation/Mannich reaction. Initiated by
      expeditious assembly of bridgehead heterofunctionalization in the [3.3.1]
      bicyclic system of lycodoline, a novel tandem palladium-mediated oxidative
      dehydrogenation/hetero-Michael reaction has been developed for the strain-driven
      formation of the C-heteroatom bond, leading to a new approach to conformationally
      rigid bridgehead heteroquaternary carbons. The present unified strategy provides
      a scenario for the divergent total syntheses of nine natural Lycopodium alkaloids
      and four unnatural C12 epimers, wherein (+/-)-lycojaponicumin D and six
      lycodoline-type alkaloids have been synthetically achieved for the first time.

PMID- 28448137
TI  - Profiling the Phenolic Compounds of the Four Major Seed Coat Types and Their
      Relation to Color Genes in Lentil.
AB  - Phenolic compounds can provide antioxidant health benefits for humans, and foods
      such as lentils can be valuable dietary sources of different subclasses of these
      secondary metabolites. This study used LC-MS analyses to compare the phenolic
      profiles of lentil genotypes with four seed coat background colors (green, gray,
      tan, and brown) and two cotyledon colors (red and yellow) grown at two locations.
      The mean area ratio per mg sample (MARS) values of various phenolic compounds in
      lentil seeds varied with the different seed coat colors conferred by specific
      genotypes. Seed coats of lentil genotypes with the homozygous recessive tgc
      allele (green and gray seed coats) had higher MARS values of flavan-3-ols,
      proanthocyanidins, and some flavonols. This suggests lentils featuring green and
      gray seed coats might be more promising as health-promoting foods.

PMID- 28448136
TI  - Cucurbitane Glucosides from the Crude Extract of Siraitia grosvenorii with
      Moderate Effects on PGC-1alpha Promoter Activity.
AB  - Seven new cucurbitane glucosides, 11-oxomogrosides III E and IV (1 and 2), 11
      oxoisomogroside V (3), 7-oxomogrosides III E and IV (4 and 5), and mogrosides VI
      A and VI B (6 and 7), were separated from the crude extract of Siraitia
      grosvenorii. The new structures were defined by analysis of their 1H and 13C NMR,
      2D NMR, and HRESIMS data. Especially, the band-selective constant time HSQC and
      band-selective constant time HMBC techniques were recuited to elucidate the
      structures of the complex glucoside moieties. Using the PGC-1alpha promoter
      driven luciferase reporter assay, the isolated compounds were examined for PGC
      1alpha promoter activity.

PMID- 28448138
TI  - The IDP-Specific Force Field ff14IDPSFF Improves the Conformer Sampling of
      Intrinsically Disordered Proteins.
AB  - Intrinsically disordered proteins (IDPs) or intrinsically disordered regions do
      not have a fixed tertiary structure but play key roles in signal regulation,
      molecule recognition, and drug targeting. However, it is difficult to study the
      structure and function of IDPs by traditional experimental methods because of
      their diverse conformations. Limitations of current generic protein force fields
      and solvent models were reported in the previous simulations of IDPs. We have
      also explored overcoming these limitations by developing the ff99IDPs and
      ff14IDPs force fields to correct the dihedral distribution for eight disorder
      promoting residues often observed in IDPs and found encouraging improvements.
      Here we extend our correction of backbone dihedral terms to all 20 naturally
      occurring amino acids in the IDP-specific force field ff14IDPSFF to further
      improve the quality of the modeling of IDPs. Extensive tests of seven IDPs and 14
      unstructured short peptides show that the simulated Calpha chemical shifts
      obtained with the ff14IDPSFF force field are in quantitative agreement with those
      from NMR experiments and are more accurate than those obtained with the base
      generic force field and also our previous ff14IDPs that only corrects the eight
      disorder-promoting amino acids. The influence of the solvent model was also
      investigated and found to be less important. Finally, our explicit-solvent MD
      simulations further show that ff14IDPSFF can still be used to model structural
      and dynamical properties of two tested folded proteins, with a slightly better
      agreement in the loop regions for both structural and dynamical properties. These
      findings confirm that the newly developed IDP-specific force field ff14IDPSFF can
      improve the conformer sampling of intrinsically disordered proteins.

PMID- 28448139
TI  - Intermittent Aeration Suppresses Nitrite-Oxidizing Bacteria in Membrane-Aerated
      Biofilms: A Model-Based Explanation.
AB  - Autotrophic ammonium oxidation in membrane-aerated biofilm reactors (MABRs) can
      make treatment of ammonium-rich wastewaters more energy-efficient, especially
      within the context of short-cut ammonium removal. The challenge is to exclusively
      enrich ammonium-oxidizing bacteria (AOB). To achieve nitritation, strategies to
      suppress nitrite-oxidizing bacteria (NOB) are needed, which are ideally grounded
      on an understanding of underlying mechanisms. In this study, a nitrifying MABR
      was operated under intermittent aeration. During eight months of operation, AOB
      dominated, while NOB were suppressed. On the basis of dissolved oxygen (DO),
      ammonium, nitrite, and nitrate profiles within the biofilm and in the bulk, a 1
      dimensional nitrifying biofilm model was developed and calibrated. The model was
      utilized to explore the potential mechanisms of NOB suppression associated with
      intermittent aeration, considering DO limitation, direct pH effects on enzymatic
      activities, and indirect pH effects on activity via substrate speciation. The
      model predicted strong periodic shifts in the spatial gradients of DO, pH, free
      ammonia, and free nitrous acid, associated with aerated and nonaerated phases.
      NOB suppression during intermittent aeration was mostly explained by periodic
      inhibition caused by free ammonia due to periodic transient pH upshifts.
      Dissolved oxygen limitation did not govern NOB suppression. Different
      intermittent aeration strategies were then evaluated for nitritation success in
      intermittently aerated MABRs: both aeration intermittency and duration were
      effective control parameters.

PMID- 28448140
TI  - Essentially Trap-Free CsPbBr3 Colloidal Nanocrystals by Postsynthetic Thiocyanate
      Surface Treatment.
AB  - We demonstrate postsynthetic modification of CsPbBr3 nanocrystals by a
      thiocyanate salt treatment. This treatment improves the quantum yield of both
      freshly synthesized (PLQY ~ 90%) and aged nanocrystals (PLQY ~ 70%) to within
      measurement error (2-3%) of unity, while simultaneously maintaining the shape,
      size, and colloidal stability. Additionally, the luminescence decay kinetics
      transform from multiexponential decays typical of nanocrystalline semiconductors
      with a distribution of trap sites, to a monoexponential decay, typical of single
      energy level emitters. Thiocyanate only needs to access a limited number of
      CsPbBr3 nanocrystal surface sites, likely representing under-coordinated lead
      atoms on the surface, in order to have this effect.

PMID- 28448141
TI  - Correction to Design of Potent and Druglike Nonphenolic Inhibitors for Catechol O
      Methyltransferase Derived from a Fragment Screening Approach Targeting the S
      Adenosyl-l-methionine Pocket.

PMID- 28448142
TI  - Bottleneck Effect of N,N-Dimethylformamide in InOF-1: Increasing CO2 Capture in
      Porous Coordination Polymers.
AB  - The bottleneck effect of confined N,N-dimethylformamide (DMF) molecules was
      observed in InOF-1 for the first time: CO2 capture was remarkably enhanced in
      samples of as-synthesized InOF-1, thermally activated in such a way that a small
      residual amount of DMF molecules remained confined within the pores (DMF@InOF-1).
      Dynamic CO2 adsorption experiments on DMF@InOF-1 exhibited a CO2 capture of 8.06
      wt % [1.5-fold higher than that of a fully activated InOF-1 (5.24%)]. DMF@InOF-1
      can reversibly adsorb/desorb 8.09% CO2 with no loss of CO2 capacity after 10
      cycles, and the desorption is accomplished by only turning the CO2 flow off.
      Static CO2 adsorption experiments (at 196 K) demonstrated a 1.4-fold CO2 capture
      increase (from 5.5 mmol.g-1, fully activated InOF-1, to 7.5 mmol.g-1, DMF@InOF
      1). Therefore, these CO2 capture properties are the result of the presence of
      residual-confined DMF molecules within the InOF-1 framework and their
      interactions via a very strong hydrogen bond with the In2(MU-OH) groups, which
      prevent DMF leaching. The stability of this hydrogen bond is given by a perfect
      fit of the DMF molecule in the "dent" around the OH group that allows a nearly
      ideal orientation of the DMF molecule towards the OH group.

PMID- 28448143
TI  - Effect-Directed Analysis of Toxicants in Sediment with Combined Passive Dosing
      and in Vivo Toxicity Testing.
AB  - Identifying key toxicants in sediment is a great challenge, particularly if
      nontarget toxicants are involved. To identify the contaminants responsible for
      sediment toxicity to Chironomus dilutus in Guangzhou reach of the Pearl River in
      South China, passive dosing and in vivo toxicity testing were incorporated into
      effect-directed analysis (EDA) to account for bioavailability. Fractionation of
      sediment extracts was performed with gel permeation chromatography and reverse
      phase liquid chromatography sequentially. Polydimethylsiloxane served as passive
      dosing matrix for midge bioassays. The fractions showing abnormal enzymatic
      response were subject to a nontarget analysis, which screened out 15 candidate
      toxicants. The concentrations of the screened contaminants (log-based organic
      carbon normalized) in sediments of 10 sites were compared to sediment toxicity
      (10 and 20 day mortality and 10 day enzymatic response) to C. dilutus using
      correlation analyses. The results suggested that oxidative stress induced by
      cypermethrin, dimethomorph, pebulate and thenylchlor may have in part caused the
      observed toxicity to C. dilutus. The present study shows that EDA procedures
      coupled with passive dosing and in vivo toxicity testing can be effective in
      identifying sediment-bound toxicants, which may pose high risk to benthic
      organisms but are not routinely monitored and/or regulated. The findings of the
      present study highlight the importance of incorporating environmentally relevant
      approaches in assessing sediment heavily impacted by a multitude of contaminants,
      which is often the case in many developing countries.

PMID- 28448145
TI  - Coarse-Grained Molecular Dynamics Model of Double-Stranded DNA for DNA
      Nanostructure Design.
AB  - A new coarse-grained molecular dynamics double-stranded DNA model (nCG-dsDNA
      model) using an improved beads-spring model was proposed. In this model,
      nucleotide comprising phosphate, sugar, and base group were replaced by a single
      bead. The double stranded model with 202 base pairs was created to tune the
      parameters of the bond, the nonbond, stack, angle bending, and electrostatic
      interaction. The average twisted angle and the persistence length of the model
      without electrostatic interaction were calculated at 35.3 degrees  and 120.3 bp,
      confirming that the proposed model successfully realized the experimentally
      observed double-stranded DNA structure. Moreover, the model with electrostatic
      interaction was discussed. From calculation results, we confirmed that the
      dependency of the salt concentration on the persistence length of the nCG-dsDNA
      model at the 30% charge is in good agreement with the Poisson-Boltzmann
      theoretical model.

PMID- 28448144
TI  - A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid
      Tripeptide from the Marine Cyanobacterium Moorea producens.
AB  - Genome sequencing of microorganisms has revealed a greatly increased capacity for
      natural products biosynthesis than was previously recognized from compound
      isolation efforts alone. Hence, new methods are needed for the discovery and
      description of this hidden secondary metabolite potential. Here we show that
      provision of heavy nitrogen 15N-nitrate to marine cyanobacterial cultures
      followed by single-filament MALDI analysis over a period of days was highly
      effective in identifying a new natural product with an exceptionally high
      nitrogen content. The compound, named cryptomaldamide, was subsequently isolated
      using MS to guide the purification process, and its structure determined by 2D
      NMR and other spectroscopic and chromatographic methods. Bioinformatic analysis
      of the draft genome sequence identified a 28.7 kB gene cluster that putatively
      encodes for cryptomaldamide biosynthesis. Notably, an amidinotransferase is
      proposed to initiate the biosynthetic process by transferring an amidino group
      from arginine to serine to produce the first residue to be incorporated by the
      hybrid NRPS-PKS pathway. The maldiisotopic approach presented here is thus
      demonstrated to provide an orthogonal method by which to discover novel chemical
      diversity from Nature.

PMID- 28448146
TI  - Radical Nitration-Debromination of alpha-Bromo-alpha-fluoroalkenes as a
      Stereoselective Route to Aromatic alpha-Fluoronitroalkenes-Functionalized
      Fluorinated Building Blocks for Organic Synthesis.
AB  - A new highly efficient method for the synthesis of 2-fluoro-2-nitrostyrenes was
      described. Radical nitration of readily available 2-bromo-2-fluorostyrenes with
      Fe(NO3)3.9H2O resulted in the formation of the corresponding alpha-fluoro
      nitroalkenes in isolated yields up to 92%. The reaction proceeded as a nitration
      debromination sequence to highly stereoselectively give alpha-fluoro-nitroalkenes
      as Z-isomers only. The broad scope of this method was demonstrated. Prepared
      monofluorinated alkenes were shown to be versatile building blocks for the
      synthesis of various fluorinated products.

PMID- 28448147
TI  - Binding of Small Gas Molecules by Metal-Bipyridyl Monocationic Complexes (Metal =
      Cu, Ag, Au) and Possible Bond Activations Therein.
AB  - The viability of a series of small gas molecules (H2, N2, CO, CO2, H2O, H2S,
      C2H2, CH4, CH3Cl, C2H4, and C2H6) bound [M-(bipy)]+ (bipy = bipyridyl; M = Cu,
      Ag, Au) complexes is investigated at the PBE0/cc-pVTZ/cc-pVTZ-PP level with a
      special emphasis on the possible bond activation within the bound ligands. While
      the bond dissociation energy, enthalpy change, and free energy change are
      computed to show the stability of the complexes with respect to the dissociation
      into [M-(bipy)]+ and free gas molecule (L), natural bond orbital, electron
      density, and energy decomposition analyses in conjunction with natural orbitals
      for chemical valence are carried out to characterize the nature of L-M bonds. For
      a given L, the L binding ability is the highest for Au followed by Cu and Ag
      complexes, except for quite loosely bound CO2. For all ligand cases, the
      dissociation processes from the respective bound complexes are endergonic in
      nature at room temperature, except for the H2-, CH4-, and C2H6-bound Ag complexes
      and CO2-bound Ag and Au complexes. The interaction between L and M centers is
      supported by orbital and ionic interactions with latter being more dominant over
      the former. The delocalization index and local energy density values support the
      covalent character in L-M bonds in most of the cases. These M centers can act as
      a mild bond activation agent for L, Au being the best candidate in this series
      for this purpose. Particularly, the H-H bond in H2, C?C bond in C2H4, C=C bond in
      C2H2, and C-H bonds in CH4 and C2H6 (the last two are for Au) are elongated along
      with a significant red-shift in the corresponding stretching frequency, compared
      to those in free molecules. These can be explained by the significant pi-back
      donation populating the lowest unoccupied antibonding molecular orbital of L in
      these complexes.

PMID- 28448148
TI  - Tryptophan to Arginine Substitution in Puroindoline-b Alters Binding to Model
      Eukaryotic Membrane.
AB  - We have studied how puroindoline-b (PINB) mutants bind to model eukaryotic
      membranes dependent on binary composition of anionic:zwitterionic phospholipids
      and the presence of cholesterol and sphingomyelin in the model membrane. We have
      found that the trends in lipid binding behavior are different for wild-type PINB
      compared to its naturally occurring PINB(Trp44Arg) mutant form and have seen
      evidence of protein-induced domain formation within the lipid layer structure.
      Results show that selective binding of antimicrobial peptides to different
      membrane types is as a result of differences in lipid composition and the
      arrangement of lipids within the membrane surface. However, membrane-binding
      behavior is not easily predicted; it is determined by net charge, hydrophobicity,
      and the amphiphilicity of the protein/peptide lipid-binding domain.

PMID- 28448149
TI  - Hofmeister Effect on PNIPAM in Bulk and at an Interface: Surface Partitioning of
      Weakly Hydrated Anions.
AB  - The effect of sodium fluoride, sodium trichloroacetate, and sodium thiocyanate on
      the stability and conformation of poly(N-isopropylacrylamide), in bulk solution
      and at the gold-aqueous interface, is investigated by differential scanning
      calorimetry, dynamic light scattering, quartz crystal microbalance, and atomic
      force microscopy. The results indicate a surface partitioning of the weakly
      hydrated anions, i.e., thiocyanate and trichloroacetate, and the findings are
      discussed in terms of anion-induced electrostatic stabilization. Although
      attractive polymer-ion interactions are suggested for thiocyanate and
      trichloroacetate, a salting-out effect is found for sodium trichloroacetate. This
      apparent contradiction is explained by a combination of previously suggested
      mechanisms for the salting-out effect by weakly hydrated anions.

PMID- 28448150
TI  - Electrostatic Screening of Charged Defects in Monolayer MoS2.
AB  - Defects in monolayer transition-metal dichalcogenides (TMDCs) may lead to
      unintentional doping, charge-carrier trapping, and nonradiative recombination.
      These effects impair electronic and optoelectronic technologies. Here we show
      that charged defects in MoS2 monolayers can be effectively screened when they are
      in contact with an ionic liquid (IL), leading to an increase in photoluminescence
      (PL) yield by up to two orders of magnitude. The extent of this PL enhancement by
      the IL correlates with the brightness of each pretreated sample. We propose the
      existence of two classes of nonradiative recombination centers in monolayer MoS2:
      (i) charged defects that relate to unintentional doping and may be
      electrostatically screened by ILs and (ii) neutral defects that remain unaffected
      by the presence of ILs.

PMID- 28448151
TI  - Methoxysulfinyl Radical CH3OSO: Gas-Phase Generation, Photochemistry, and
      Oxidation.
AB  - Methylsulfoxide radicals CH3SOx (x = 1-4) are key reactive sulfur species (RSS)
      in the atmospheric oxidation of volatile organic sulfur compounds (VOSCs).
      Through flash vacuum pyrolysis (FVP) of trifluoromethanesulfinic acid methyl
      ester CF3S(O)OCH3 at 1000 K, the methoxysulfinyl radical CH3OSO has been
      generated in the gas phase and subsequently characterized in cryogenic N2, Ar,
      and Ne matrices by IR spectroscopy. Upon 266 nm laser irradiation, CH3OSO
      efficiently isomerizes to the less stable methylsulfonyl radical CH3SO2 in
      matrices without noticeable decomposition. In the gas phase, CH3OSO reacts with
      O2 and yields sulfinyl peroxyl radical CH3OS(O)OO, a new member in the CH3SOx (x
      = 1-4) family. This radical dissociates into SO3 and CH3O with the intermediacy
      of the sulfonyoxyl radical CH3OSO3 under the 266 nm laser irradiation.
      Additionally, the photoisomerization of CF3S(O)OCH3 to sulfenic ester CF3OSOCH3
      was also observed.

PMID- 28448152
TI  - Enantioselective and Diastereoselective Construction of Chiral Amino Alcohols by
      Iridium-f-Amphox-Catalyzed Asymmetric Hydrogenation via Dynamic Kinetic
      Resolution.
AB  - The iridium-f-amphox-catalyzed asymmetric hydrogenation of racemic alpha-amino
      beta-unfunctionalized ketones proceeds via a DKR (dynamic kinetic resolution)
      process for the construction of various chiral N,N-disubstituted alpha-amino beta
      unfunctionalized alcohols in quantitative yields with excellent
      enantioselectivities and diastereoselectivities (all products >99% ee and >99:1
      dr, TON up to 100 000). Importantly, this catalytic asymmetric hydrogenation with
      a DKR process provided a highly efficient and powerful synthetic strategy for the
      preparation of key chiral intermediates of the preclinical antitumor agent (S,S)
      R116010.

PMID- 28448153
TI  - Thermal Stability of Metal Nanocrystals: An Investigation of the Surface and Bulk
      Reconstructions of Pd Concave Icosahedra.
AB  - Despite the remarkable success in controlling the synthesis of metal
      nanocrystals, it still remains a grand challenge to stabilize and preserve the
      shapes or internal structures of metastable kinetic products. In this work, we
      address this issue by systematically investigating the surface and bulk
      reconstructions experienced by a Pd concave icosahedron when subjected to heating
      up to 600  degrees C in vacuum. We used in situ high-resolution transmission
      electron microscopy to identify the equilibration pathways of this far-from
      equilibrium structure. We were able to capture key structural transformations
      occurring during the thermal annealing process, which were mechanistically
      rationalized by implementing self-consistent plane-wave density functional theory
      (DFT) calculations. Specifically, the concave icosahedron was found to evolve
      into a regular icosahedron via surface reconstruction in the range of 200-400 
      degrees C, and then transform into a pseudospherical crystalline structure
      through bulk reconstruction when further heated to 600  degrees C. The
      mechanistic understanding may lead to the development of strategies for enhancing
      the thermal stability of metal nanocrystals.

PMID- 28448154
TI  - Improving Lithium-Sulfur Battery Performance under Lean Electrolyte through
      Nanoscale Confinement in Soft Swellable Gels.
AB  - Li-S batteries have been extensively studied using rigid carbon as the host for
      sulfur encapsulation, but improving the properties with a reduced electrolyte
      amount remains a significant challenge. This is critical for achieving high
      energy density. Here, we developed a soft PEO10LiTFSI polymer swellable gel as a
      nanoscale reservoir to trap the polysulfides under lean electrolyte conditions.
      The PEO10LiTFSI gel immobilizes the electrolyte and confines polysulfides within
      the ion conducting phase. The Li-S cell with a much lower electrolyte to sulfur
      ratio (E/S) of 4 gE/gS (3.3 mLE/gS) could deliver a capacity of 1200 mA h/g, 4.6
      mA h/cm2, and good cycle life. The accumulation of polysulfide reduction
      products, such as Li2S, on the cathode, is identified as the potential mechanism
      for capacity fading under lean electrolyte conditions.

PMID- 28448155
TI  - Cp*Co(III)-Catalyzed Annulation of Carboxylic Acids with Alkynes.
AB  - A new procedure for oxidative coupling of aromatic and acrylic acids with alkynes
      has been developed using abundant, nontoxic, and air stable Cp*Co(III) catalyst.
      The coupling involves initial cyclometalation via weak chelation-assisted C-H
      bond activation followed by alkyne coordination, insertion, and reductive
      elimination leading to diverse isocoumarins (alpha-pyranones) in good yields
      under mild conditions.

PMID- 28448156
TI  - Traceless Directing-Group Strategy in the Ru-Catalyzed, Formal [3 + 3] Annulation
      of Anilines with Allyl Alcohols: A One-Pot, Domino Approach for the Synthesis of
      Quinolines.
AB  - A unique, ruthenium-catalyzed, [3 + 3] annulation of anilines with allyl alcohols
      in the synthesis of substituted quinolines is reported. The method employs a
      traceless directing group strategy in the proximal C-H bond activation and
      represents a one-pot Domino synthesis of quinolines from anilines.

PMID- 28448157
TI  - Protein changes in Lepidium sativum L. exposed to Hg during soil
      phytoremediation.
AB  - Some investigations have been carried out in this study to find the best
      technique of soil reclamation in mercurypolluted soil. In this study, we examined
      Lepidium sativum L. as a plant useful for Hg phytoextraction. The simultaneous
      application of compost and thiosulfate was explored as a possible method of
      enhancing the process of phytoextraction. The results of the investigations of
      plant protein changes during assisted Hg phytoextraction were also provided. The
      results of the study show that combined use of compost and thiosulfate
      significantly increased both the total Hg accumulation and its translocation to
      aerial plant tissues. Plant protein analysis showed that L. sativum L. has the
      ability to respond to environmental stress condition by the activation of
      additional proteins. The additional proteins, like homocysteine
      methyltransferase, ribulose bisphosphate carboxylases (long and short chains), 14
      3-3-like protein, and biosynthesis-related 40S ribosomal protein S15, were
      activated in plant shoots only in experiments carried out in Hg-polluted soil.
      There were no protein changes observed in plants exposed to compost and
      thiosulfate. It suggests that the combined use of compost and thiosulfate
      decreased Hg toxicity.

PMID- 28448158
TI  - Corrigendum.

PMID- 28448159
TI  - The Centrality of the Response Process in Construct Validity: An Illustration via
      the Rorschach Space Response.
AB  - Recently, psychologists have emphasized the response process-that is, the
      psychological operations and behaviors that lead to test scores-when designing
      psychological tests, interpreting their results, and refining their validity. To
      illustrate the centrality of the response process in construct validity and test
      interpretation, we provide a historical, conceptual, and empirical review of the
      main uses of the background white space of the Rorschach cards, called space
      reversal (SR) and space integration (SI) in the Rorschach Performance Assessment
      System. We show how SR and SI's unique response processes result in different
      interpretations, and that reviewing their literatures with these distinct
      interpretations in mind produces the expected patterns of convergent and
      discriminant validity. That is, SR was uniquely related to measures of
      oppositionality; SI was uniquely related to measures of cognitive complexity; and
      both SR and SI were related to measures of creativity. Our review further
      suggests that the Comprehensive System use of a single space code for all uses of
      white space likely led to its lack of meta-analytic support as a measure of
      oppositionality (Mihura, Meyer, Dumitrascu, & Bombel, 2013 ). We close by
      discussing the use of the response process to improve test interpretation,
      develop better measures, and advance the design of research.

PMID- 28448161
TI  - Peaches for Lunch: Creating and Using Visual Variables.
AB  - In this article, I describe the process of systematically including nonverbal
      data in medical anthropology research. I demonstrate the process of visualizing
      and coding videotaped moments of life and show how we can analyze what is being
      done along with what is being said. I ground my discussion in toddler language
      socialization and then expand my observations to the realm of language
      pathologies. Aphasia from strokes, speech difficulties in neurologically based
      illnesses like Lou Gehrig's disease, and the variety of communication challenges
      that face those on the autism spectrum can all be studied in interesting ways by
      including precise descriptions of nonverbal actions. I discuss the process of
      recording and coding the data with the software Observer XT 11.5 by Noldus. This
      method of collecting and analyzing video data can be used for many
      anthropological questions, in addition to those concerned with communication.

PMID- 28448160
TI  - Validation of ANAM for cognitive screening in a mixed clinical sample.
AB  - The Automated Neuropsychological Assessment Metrics (ANAM) is a library of
      computer based tests designed to measure cognitive function at a single time
      point or longitudinally for detection of cognitive change. This study sought to
      validate ANAM as a cognitive screening tool for presence of confirmed
      neuropsychological diagnosis in an outpatient setting. Retrospective data
      analysis was conducted for 139 patients referred for outpatient
      neuropsychological assessment. Clinical diagnosis was made independent of ANAM
      test results and resulted in a diagnostic mix of both neurologic and psychologic
      etiologies. ANAM scores predictive of presence of confirmed diagnosis were
      identified using multiple logistic regression and the predictive ability of the
      resulting model was quantified using receiver operator characteristic analysis.
      Sensitivity and specificity for the ANAM when combined with anger and depressive
      symptom scores were 71% and 91%, respectively, with a positive predictive value
      of 97.5 and negative predictive value of 40.4. This combined approach provided
      the greatest accuracy for individual tests as well as the composite score of the
      ANAM in identifying those who received a subsequent clinical diagnosis. Although
      data should be replicated in larger samples, these results suggest that ANAM may
      have predictive value and may be a useful screening tool for identifying those
      who would likely benefit from neuropsychological services.

PMID- 28448163
TI  - The interplay between feelings and beliefs about condoms as predictors of their
      use.
AB  - OBJECTIVE: Negative feelings about condoms are a key barrier to their use. Using
      the behavioural affective associations model, we examined the joint effects of
      affective associations and cognitive beliefs about condoms on condom use. DESIGN:
      In Study 1 (N = 97), students completed measures of their affective associations
      and cognitive beliefs about sex and condoms, sexual activity and condom use. In
      Study 2 (N = 171), a measure of behavioural intentions and condom selection task
      were added. MAIN OUTCOME MEASURES: Condom use measured in Study 1 as (1) current
      condom use, and (2) willingness to use condoms; in Study 2 as: (1) behavioural
      intentions, (2) number of condoms selected. RESULTS: Affective associations with
      sex and condoms were behaviour-specific, were directly associated with the
      respective behaviour, and mediated the relations of cognitive beliefs to
      behaviour, ps < .05. In Study 2, affective associations were associated with
      behavioural intentions and the number of condoms selected, ps < .05; cognitive
      beliefs were indirectly associated with these outcomes through affective
      associations, indirect effects: ps < .05. CONCLUSIONS: Affective associations are
      a behaviour-specific and proximal predictor of condom use, mediating the effect
      of cognitive beliefs, suggesting they may be a particularly viable intervention
      target.

PMID- 28448164
TI  - Increasing use of cannabis among arrested drivers in Norway.
AB  - OBJECTIVE: The availability of cannabis in Norway seems to have increased
      according to seizures by customs and police. On the other hand, national
      population surveys have not found any increase in self-reported use of cannabis.
      This investigation aimed at studying trends in cannabis use among suspected drug
      impaired drivers apprehended by the police in Norway. METHODS: A time series
      observational study of cannabis use among all drivers tested for drugs during
      2000-2015 was performed. Descriptive analyses of trends in frequencies and
      combined use of cannabis with other drugs or alcohol for different age groups and
      gender were conducted. RESULTS: Tetrahydrocannabinol (THC) is the main
      psychoactive substance in cannabis and was detected in blood samples from 18,767
      suspected drug-impaired drivers. The annual number of THC findings increased
      during the years 2000-2015 for all age groups. For cannabis-only users, young
      drivers aged 20-29 years dominated during the whole period, whereas for multidrug
      cannabis users the median age increased steadily during 2000-2015. After 2009,
      the annual increase in THC findings escalated; THC-only findings increased the
      most. CONCLUSIONS: Increasing numbers of THC-positive drivers were found among
      all age groups and genders; the strongest trend was observed between 2009-2015
      for young drivers testing positive only for THC.

PMID- 28448165
TI  - Phytoremediation of organochlorine and pyrethroid pesticides by aquatic
      macrophytes and algae in freshwater systems.
AB  - Extensive use of Pesticides in agriculture and its surface runoff in river water
      is a major environmental concern. The present study evaluated the
      phytoremediation potential of Eichornia crassipes, Pistia strateotes and algae
      (Chaetomorpha sutoria, Sirogonium sticticum and Zygnema sp.) for organochlorine
      and pyrethroid pesticides. Water and plant samples were extracted by liquid phase
      and solid phase extraction respectively and analyzed by high-performance liquid
      chromatography. Eleven treatments (T1-T11) with and without plants were used for
      phytoremediation of organochlorine and pyrethroid pesticides. During the
      experiment, P. strateotes, E. crassipes and algae (C. sutoria, S. sticticum and
      Zygnema sp.) showed the highest removal efficiency with 62 (71% root, 29% shoot),
      60 (67% root, 33% shoot), and 58% respectively for organochlorine and 76 (76%
      root, 24% shoot), 68 (69% root, 31% shoot), and 70% respectively for pyrethroids
      for the respective aquatic plants. Dissipation rate constant of treatments with
      plants (T2, T3, T5, T6, T8, and T9) was significantly higher (p < 0.05) as
      compared to that of treatments without plants (T10 and T11, control) for both
      organochlorine and pyrethroid. The bioconcentration factor of pyrethroid
      treatments (T3, T6, and T9) was significantly higher (p < 0.05) as compared to
      that of organochlorine treatments (T2, T5 and T8). The removal efficiency of E.
      crassipes, P. strateotes and algae (C. sutoria, S. sticticum and Zygnema sp.) for
      pyrethroids was significantly higher (p < 0.01) as compared to that of
      organochlorine.

PMID- 28448166
TI  - Changes in motorcycle-related injuries and deaths after mandatory motorcycle
      helmet law in a district of Vietnam.
AB  - OBJECTIVE: Our study measured the change in head injuries and deaths among
      motorcycle users in Cu Chi district, a suburban district of Ho Chi Minh City.
      METHODS: Hospital records for road traffic injuries (RTIs) were collected from
      the Cu Chi Trauma Centre and motorcycle-related death records were obtained from
      mortality registries in commune health offices. Head injury severity was
      categorized using the Abbreviated Injury Score (AIS). Rate ratios (RRs) were used
      to compare rates pre- and post-law (2005/2006-2009/2010). Cu Chi's population,
      stratified by year, age, and sex, was used as the denominator. RESULTS: Of
      records identifying the transportation mode at the time of injury, motorcyclists
      accounted for most injuries (3,035, 87%) and deaths (238, 90%). Head injuries
      accounted for 70% of motorcycle-related hospitalizations. Helmet use was not
      recorded in any death records and not in 97% of medical records. Males accounted
      for most injuries (73%) and deaths (88%). The median age was 28 years and 32
      years for injuries and deaths, respectively. Compared to the pre-law period,
      rates of motorcycle injuries (RR = 0.53; 95% confidence interval [CI], 0.49
      0.58), head injuries (RR = 0.35; 95% CI, 0.31-0.39), severe head injuries (RR =
      0.47; 95% CI, 0.34-0.63), and deaths (RR = 0.69; 95% CI, 0.53-0.89) significantly
      decreased in the post-law period. CONCLUSIONS: Rates of head injuries and deaths
      among motorcycle riders decreased significantly after implementation of the
      mandatory helmet law in Vietnam. To further examine the impact of the motorcycle
      helmet law, including compliance and helmet quality, further emphasis should be
      placed on gathering helmet use data from injured motorcyclists.

PMID- 28448167
TI  - Standardized error severity score (ESS) ratings to quantify risk associated with
      child restraint system (CRS) and booster seat misuse.
AB  - OBJECTIVE: Although numerous research studies have reported high levels of error
      and misuse of child restraint systems (CRS) and booster seats in experimental and
      real-world scenarios, conclusions are limited because they provide little
      information regarding which installation issues pose the highest risk and thus
      should be targeted for change. Beneficial to legislating bodies and researchers
      alike would be a standardized, globally relevant assessment of the potential
      injury risk associated with more common forms of CRS and booster seat misuse,
      which could be applied with observed error frequency-for example, in car seat
      clinics or during prototype user testing-to better identify and characterize the
      installation issues of greatest risk to safety. METHODS: A group of 8 leading
      world experts in CRS and injury biomechanics, who were members of an
      international child safety project, estimated the potential injury severity
      associated with common forms of CRS and booster seat misuse. These injury risk
      error severity score (ESS) ratings were compiled and compared to scores from
      previous research that had used a similar procedure but with fewer respondents.
      To illustrate their application, and as part of a larger study examining CRS and
      booster seat labeling requirements, the new standardized ESS ratings were applied
      to objective installation performance data from 26 adult participants who
      installed a convertible (rear- vs. forward-facing) CRS and booster seat in a
      vehicle, and a child test dummy in the CRS and booster seat, using labels that
      only just met minimal regulatory requirements. The outcome measure, the risk
      priority number (RPN), represented the composite scores of injury risk and
      observed installation error frequency. RESULTS: Variability within the sample of
      ESS ratings in the present study was smaller than that generated in previous
      studies, indicating better agreement among experts on what constituted injury
      risk. Application of the new standardized ESS ratings to installation performance
      data revealed several areas of misuse of the CRS/booster seat associated with
      high potential injury risk. CONCLUSIONS: Collectively, findings indicate that
      standardized ESS ratings are useful for estimating injury risk potential
      associated with real-world CRS and booster seat installation errors.

PMID- 28448162
TI  - Joblessness and Lost Earnings after Acute Respiratory Distress Syndrome in a 1
      Year National Multicenter Study.
AB  - RATIONALE: Following acute respiratory distress syndrome (ARDS), joblessness is
      common but poorly understood. OBJECTIVES: To evaluate the timing of return to
      work after ARDS, and associated risk factors, lost earnings, and changes in
      healthcare coverage Methods: Over 12-month longitudinal follow-up, ARDS survivors
      from 43 U.S. ARDSNet hospitals provided employment and healthcare coverage data
      via structured telephone interviews. Factors associated with the timing of return
      to work were assessed using Fine and Gray regression analysis. Lost earnings were
      estimated using Bureau of Labor Statistics data. MEASUREMENTS AND MAIN RESULTS:
      Of 922 consenting survivors, 386 (42%) were employed before ARDS (56% male; mean
      +/- SD age, 45 +/- 13 yr), with seven dying by 12-month follow-up. Of 379
      previously employed 12-month survivors, 166 (44%) were jobless at 12-month follow
      up. Accounting for competing risks of death and retirement, half of enrolled and
      previously employed survivors returned to work by 13 weeks after hospital
      discharge, with 68% ever returning by 12 months. Delays in return to work were
      associated with longer hospitalization and older age among nonwhite survivors.
      Over 12-month follow-up, 274 (71%) survivors accrued lost earnings, averaging
      $26,949 +/- $22,447 (60% of pre-ARDS annual earnings). Jobless survivors
      experienced a 14% (95% confidence interval, 5-22%; P = 0.002) absolute decrease
      in private health insurance (from 44% pre-ARDS) and a 16% (95% confidence
      interval, 7-24%; P < 0.001) absolute increase in Medicare and Medicaid (from
      33%). CONCLUSIONS: At 12 months after ARDS, nearly one-half of previously
      employed survivors were jobless. Post-ARDS joblessness is associated with readily
      identifiable patient and hospital variables and accompanied by substantial lost
      earnings and a shift toward government-funded healthcare coverage.

PMID- 28448168
TI  - Management of textile wastewater for improving growth and yield of field mustard
      (Brassica campestris L.).
AB  - Disposal of industrial wastewater is a current issue of urbanization. However,
      this problem can be sorted out by using wastewater as an alternate source of
      irrigation after the addition of some amendment. In this way, the problem of
      disposal of wastewater not only will be resolved but also scarcity of irrigation
      water can be kept off in the future. The current research study was performed to
      evaluate the influence of different concentrations of wastewater along with canal
      water for enhancing growth and yield of field mustard. Plants were irrigated with
      different mixtures of canal water and wastewater (75:25, 50:50, 25:75, and
      00:100) in addition to canal water as control. The results revealed that
      application of 50:50% waste and canal water improved plant height, the number of
      pods plant-1, pod length, root length, root dry weight, shoot dry weight, 100
      grain weight, grain and biomass yield plant-1, and nitrogen, phosphorus, and
      potassium concentration in grain and straw up to 16%, 15%, 17%, 29%, 15%, 56%,
      25%, 41%, 35%, 20%, 52%, 45%, 20%, 44%, and 42%, respectively, over positive
      control treatment. While, nutrient uptakes and agronomic efficiency of
      fertilizers also improved by the application of 50:50% canal and wastewater
      compared to positive control treatment. Furthermore, the concentration of heavy
      metals, predominantly Cr, Cu, Cd, and Pb, was reduced in grains by application of
      50% canal water and 50% wastewater. The outcomes suggest that wastewater
      utilization along with canal water mixing might be an effective approach for
      enhancing growth and yield of field mustard.

PMID- 28448169
TI  - Decolorization and mineralization of Amaranth dye using multiple zoned aerobic
      and anaerobic baffled constructed wetland.
AB  - The objective of this study is to determine the reduction efficiency of Chemical
      Oxygen Demand (COD) as well as the removal of color and Amaranth dye metabolites
      by the Aerobic-anaerobic Baffled Constructed Wetland Reactor (ABCW). The ABCW
      reactor was planted with common reed (Phragmite australis) where the hydraulic
      retention time (HRT) was set to 1 day and was fed with synthetic wastewater with
      the addition of Amaranth dye. Supplementary aeration was supplied in designated
      compartments of the ABCW reactor to control the aerobic and anaerobic zones.
      After Amaranth dye addition the COD reduction efficiency dropped from 98 to 91%
      while the color removal efficiency was 100%. Degradation of azo bond in Amaranth
      dye is shown by the UV-Vis spectrum analysis which demonstrates partial
      degradation of Amaranth dye metabolites. The performance of the baffled unit is
      due to the longer pathway as there is the up-flow and down-flow condition
      sequentially, thus allowing more contact of the wastewater with the rhizomes and
      micro-aerobic zones.

PMID- 28448170
TI  - Mechanical circulatory support devices: methods to optimize hemodynamics during
      use.
AB  - INTRODUCTION: Mechanical circulatory support (MCS) is an increasingly utilized
      mode of therapy in the management of advanced heart failure, both as bridge to
      heart transplantation and destination therapy. As MCS becomes more prevalent, it
      is ever more important to understand the complex hemodynamics of these devices,
      as well as the strategies for hemodynamic optimization. Areas covered: This
      review provides an overview of hemodynamics in the normal human heart and the
      failing heart. We discuss the various short-term mechanical circulatory support
      devices and their hemodynamic consequences. We will then discuss the differences
      between left ventricular assist devices, and the impact of these differences on
      hemodynamics. We will describe the strategies for hemodynamic optimization using
      echocardiographic and invasive ramp studies. Finally, we will discuss the impact
      of speed changes with exercise and discuss future directions for advancements in
      MCS therapies. Expert commentary: We advocate for a deeper understanding of the
      hemodynamics underpinning MCS devices. We also recommend the more widespread use
      of ramp studies for speed optimization, which have been well validated across a
      number of different left ventricular assist device types.

PMID- 28448171
TI  - Novel investigational drugs active as single agents in multiple myeloma.
AB  - INTRODUCTION: Multiple myeloma (MM) is a hematologic malignancy characterized by
      proliferation of malignant plasma cells. patient outcome has improved markedly
      over the last decades due to the introduction of novel therapeutic agents such as
      bortezomib, thalidomide and lenalidomide. However, MM still remains largely
      incurable and patients eventually become refractory to available treatments. To
      address this unmet medical need, a variety of new molecules are currently being
      developed in preclinical models and/or are being investigated in clinical
      studies. Areas covered: We summarized available data on new investigational drugs
      showing anti-myeloma single-agent activity and that might have a role in the
      future therapeutic armamentarium against MM. Besides their single-agent activity,
      the synergic potential of these new agents with the currently approved drugs will
      be pivotal in their integration into consolidated MM backbone therapies. The
      drugs discussed include alkylators, new proteasome inhibitors, novel anti-CD38
      monoclonal antibodies, Bcl-2 inhibitors, Cyclin-Dependent-Kinase inhibitor,
      Kinesin-spindle protein inhibitors, MEK1/2 inhibitors, AKT inhibitors and PIM
      Kinase inhibitors. Expert opinion: Isatuximab, oprozomib, melflufen, venetoclax
      and filanesib seem to be the most promising agents with single agent activity.
      Nevertheless, lack of clinical activity as single agent does not imply clinical
      inefficacy in combination treatments.

PMID- 28448172
TI  - The macrophage stimulating anti-cancer agent, RRx-001, protects against ischemia
      reperfusion injury.
AB  - BACKGROUND: RRx-001, a clinical macrophage-stimulating anti-cancer agent that
      also produces nitric oxide (NO) was studied in a model of ischemia-reperfusion
      injury. METHODS: The production of NO is dependent on the oxygen tension because
      nitric oxide synthases convert l-arginine to NO and l-citrulline in the presence
      of O2. Since the P450 enzymes, which metabolize nitrate esters such as
      nitroglycerin are dependent on oxygen, the generation of 'exogenous' NO is also
      sensitive to alterations in tissue PO2. I/R injury was studied in a hamster
      chamber window, with compression of the periphery of the window for 1 h to induce
      ischemia. Animals received RRx-001 (5 mg/kg) 24 h before ischemia and sodium
      nitrite (10 nmols/kg) was supplemented 10 min after the start of reperfusion.
      Vessel diameter, blood flow, adherent leukocytes, and functional capillary
      density were assessed by intravital microscopy at 0.5, 2, and 24 h following the
      release of the ischemia. RESULTS: The results demonstrated that, compared to
      control, RRx-001 preconditioning increased blood flow and functional capillary
      density, and preserved tissue viability in the absence of side effects over a
      sustained time period. CONCLUSION: Thus, RRx-001 may serve as a long-lived
      protective agent during postsurgical restoration of flow and other ischemia
      reperfusion associated conditions, increasing blood flow and functional capillary
      density as well as preserving tissue viability in the absence of side effects.

PMID- 28448173
TI  - High beam headlamp use rates: Effects of rurality, proximity of other traffic,
      and roadway curvature.
AB  - OBJECTIVE: The few observational studies of the prevalence of high beam use
      indicate the rate of high beam use is about 25% when vehicles are isolated from
      other vehicles on unlit roads. Recent studies were limited to 2-lane rural roads
      and used measurement methods that likely overestimated use. The current study
      examined factors associated with the rate of high beam use of isolated vehicles
      on a variety of roadways in the Ann Arbor, Michigan area. METHODS: Twenty
      observation sites were categorized as urban, rural, or on a rural/urban boundary
      and selected to estimate the effects of street lighting, road curvature, and
      direction of travel relative to the city on high beam use. Sites were selected in
      pairs so that a majority of traffic passing one site also passed through the
      other. Measurement of high beams relied on video data recorded for 2 nights at
      each site, and the video data also were used to derive a precise measure of the
      proximity of other traffic. Nearly 3,200 isolated vehicles (10 s or longer from
      other vehicles) were observed, representing 1,500-plus vehicle pairs. RESULTS:
      Across the sample, 18% of the vehicles used high beams. Seventy-three percent of
      the 1,500-plus vehicle pairs used low beams at each paired site, whereas 9% used
      high beams at both sites. Vehicles at rural sites and sites at the boundaries of
      Ann Arbor were more likely to use high beams than vehicles at urban sites, but
      use in rural areas compared with rural/urban boundary areas did not vary
      significantly. Rates at all sites were much lower than expected, ranging from 0.9
      to 52.9%. High beam use generally increased with greater time between subject
      vehicles and leading vehicles and vehicles in the opposing lane. There were mixed
      findings associated with street lighting, road curvature, and direction of travel
      relative to the city. CONCLUSION: Maximizing visibility available to drivers from
      headlights includes addressing the substantial underuse of high beam headlamps.
      Advanced technologies such as high beam assist, which switches automatically
      between high and low beam headlamps depending on the presence of other traffic,
      can help to address this problem.

PMID- 28448174
TI  - A School-Based, Peer-Led, Social Marketing Intervention To Engage Spanish
      Adolescents in a Healthy Lifestyle ("We Are Cool"-Som la Pera Study): A Parallel
      Cluster Randomized Controlled Study.
AB  - BACKGROUND: Encouraging adolescents to adopt healthy lifestyles can be
      challenging. The aim of the "Som la Pera" study was to engage adolescents by
      applying new strategies to increase both their fruit and vegetable consumption
      and their physical activity (PA) while reducing their sedentary behavior.
      METHODS: In disadvantaged neighborhoods of Reus (Spain), two high schools were
      randomly assigned to the intervention (n = 170 adolescents 13- to 16-year-olds)
      and two were assigned to the control group (n = 223 adolescents 13- to 16-year
      olds). The intervention, which lasted 12 months and spanned 2 academic years
      (2013-2015), used social marketing (SM) to improve healthy choices. The peer-led
      strategy involved 5 adolescents who designed and implemented 10 activities as
      challenges for their 165 school-aged peers. The control group received no
      intervention. To assess self-reported lifestyles in both groups, the Health
      Behavior in School-Aged Children Survey was used at baseline and end of study.
      RESULTS: After 12 months, intervention adolescents showed an increase of 28.9% in
      >=1 fruit/day (p < 0.01) and of 18.5% in >=6 hours/week of PA (p < 0.01) compared
      with controls. Additionally, intervention group males had an increase of 28.8% in
      >=1 vegetable/day (p < 0.01) and of 15.6% in <=2 hours/day of sedentary activity
      (p = 0.01) compared with controls. CONCLUSIONS: A school-based, peer-led, SM
      intervention developed by adolescents attending high schools in low-income
      neighborhoods effectively improved the healthy choices of their school-aged
      peers, leading to increased fruit consumption and PA in adolescents of both
      genders. Furthermore, adolescent males were more sensitive to improvements in
      healthy choices, showing increased vegetable consumption and decreased sedentary
      behavior.

PMID- 28448175
TI  - Gaming Your Way to Health: A Systematic Review of Exergaming Programs to Increase
      Health and Exercise Behaviors in Adults.
AB  - OBJECTIVE: Adults who are not engaged by traditional exercise methods require a
      strategy to achieve and maintain sufficient physical activity for health
      benefits. Exergames, or active videogames, may motivate some adults to engage in
      physical activity. This review explored the use of exergaming to promote physical
      activity behaviors and health in adults. MATERIALS AND METHODS: A systematic
      literature review of the use of exergaming was conducted. The review included
      experimental studies with a nonclinical adult population, which measured changes
      in physical activity behaviors and changes in anthropometric healthy weight
      indicators. RESULTS: From an initial search that yielded 1644 results, nine
      articles were found to satisfy the predetermined inclusion criteria and were
      included in this review. Exergaming provided a novel method for increasing or
      substituting physical activity in the short term. Although low participation was
      not associated with anthropometric changes, significant healthy anthropometric
      changes were associated with moderate to high exergaming participation.
      CONCLUSIONS: Exergaming may be employed as an effective exercise behavior change
      strategy in the short term and may have positive health benefits if
      recommendations are made regarding intensity and duration of play for optimal
      health outcomes. However, additional research is required to evaluate the
      effectiveness of exergaming as a long-term health promotion strategy.

PMID- 28448176
TI  - Child and Adolescent Adherence With Cognitive Behavioral Therapy for Anxiety:
      Predictors and Associations With Outcomes.
AB  - Cognitive behavioral therapy (CBT) for anxiety disorders is effective, but
      nonadherence with treatment may reduce the benefits of CBT. This study examined
      (a) four baseline domains (i.e., demographic, youth clinical characteristics,
      therapy related, family/parent factors) as predictors of youth adherence with
      treatment and (b) the associations between youth adherence and treatment
      outcomes. Data were from 279 youth (7-17 years of age, 51.6% female; 79.6% White,
      9% African American), with Diagnostic and Statistical Manual of Mental Disorders
      (4th ed., text rev.) diagnoses of separation anxiety disorder, generalized
      anxiety disorder, and/or social phobia, who participated in CBT in the
      Child/Adolescent Anxiety Multimodal Study. Adherence was defined in three ways
      (session attendance, therapist-rated compliance, and homework completion).
      Multiple regressions revealed several significant predictors of youth adherence
      with CBT, but predictors varied according to the definition of adherence. The
      most robust predictors of greater adherence were living with both parents and
      fewer youth comorbid externalizing disorders. With respect to outcomes, therapist
      ratings of higher youth compliance with CBT predicted several indices of
      favorable outcome: lower anxiety severity, higher global functioning, and
      treatment responder status after 12 weeks of CBT. Number of sessions attended and
      homework completion did not predict treatment outcomes. Findings provide
      information about risks for youth nonadherence, which can inform treatment and
      highlight the importance of youth compliance with participating in therapy
      activities, rather than just attending sessions or completing homework
      assignments.

PMID- 28448177
TI  - Once-weekly dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To assess the efficacy and safety of omarigliptin and trelagliptin,
      novel dipeptidyl peptidase-4 inhibitors administered once-weekly (DPP-4i QW).
      METHODS: We systematically searched for placebo- and active-controlled randomized
      trials in adults with type 2 diabetes mellitus. RESULTS: Fifteen primary studies
      with 5709 participants were included. DPP-4i QW were more effective than placebo
      in reducing hemoglobin A1c (HbA1c) (Weighted Mean Difference (WMD) -0.63%; 95% CI
      -0.80, -0.46; I2 = 84%) and had a similar glucose-lowering effect with daily DPP
      4i (WMD 0.01%; -0.08, 0.11%; I2 = 34%). Omarigliptin was less effective compared
      with oral antidiabetic agents, other than daily DPP-4i, (WMD 0.24%; 0.10, 0.38;
      I2 = 12%). Omarigliptin did not affect body weight (WMD versus placebo 0.60 kg;
      0.25, 0.96; I2 = 0%). Risk for any hypoglycemia was similar between DPP-4i QW and
      placebo (Odds Ratio 1.32; 0.78, 2.22; I2 = 0%). Incidence of other adverse events
      did not differ between DPP-4i QW and control. CONCLUSIONS: DPP-4i QW were
      superior to placebo and similar to daily DPP-4i in terms of glycemic control, and
      were not associated with any specific adverse events. There is limited
      comparative effectiveness evidence against other agents, while their effect on
      hard clinical safety outcomes is unknown.

PMID- 28448178
TI  - What Is Being Measured? A Comparison of Two Depressive Symptom Severity
      Instruments with a Depression Diagnosis in Low-Income High-Risk Mothers.
AB  - BACKGROUND: Adequate assessment of depressive symptomatology is a necessary step
      toward decreasing income-related mental health treatment inequity. No studies
      have focused on comparing instruments used to detect depression in women from low
      income backgrounds who are mothers of young children-a period of increased risk
      for depressive symptoms. METHODS: To address this gap, two commonly used
      instruments (Center for Epidemiologic Studies Depression Scale [CES-D] and
      Hamilton Rating Scale for Depression [Hamilton]) were compared with a depression
      diagnosis (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
      [DSM-V]) in a sample (n = 251) of mothers from low-income backgrounds with
      children ranging from 1 to 54 months old. Diagnostic utility was examined in
      light of contextual factors associated with maternal depressive symptoms.
      RESULTS: In this sample, CES-D had better screening sensitivity and specificity
      than Hamilton. Our results suggest that Hamilton may underdiagnose cases of major
      depressive episodes (MDE) as defined by DSM-V among black and low-income mothers
      compared with CES-D. In addition, we identify items in CES-D, which do not
      contribute to alignment with DSM-V and are appropriate targets for future
      improvements. Our analysis identifies interpersonal relationships and mother's
      age as the primary risk factors, which differentiate between CES-D and Hamilton
      determinations versus MDE diagnosis. In addition, we find regional differences in
      CES-D and Hamilton. CONCLUSIONS: It is important to tailor the measure to the
      context, and a calibration sample should be considered for studies of sufficient
      size.

PMID- 28448179
TI  - Comparison of arterial stiffness in preeclamptic and normotensive pregnant women
      from a semi-rural region of South Africa.
AB  - BACKGROUND: Preeclampsia is associated with arterial stiffness and endothelial
      dysfunction. The pathophysiology of arterial tone in preeclampsia has not been
      well described in rural African population, where the incidence is higher.
      OBJECTIVE: The aim of the study was to compare arterial tone of preeclamptic with
      pregnant normotensive women assessed with noninvasive techniques, using
      applanation tonometry with SphygmoCor. METHOD: This was a cross-sectional study.
      Participants were recruited from Mthatha General Hospital complex Antenatal
      clinics during their third trimester. A hundred and twelve (112) normotensive and
      85 preeclamptic women (PE) were recruited into the study. Arterial stiffness was
      assessed using applanation tonometry with SphygmoCor device; central aortic
      pressures, peripheral and central augmentation index (Alx), and carotid-femoral
      pulse wave velocity (PWV) were then calculated. Data were analyzed using
      STATISTICA version 10 software. RESULTS: Pulse wave velocity was significantly
      higher in preeclamptic than normotensive women (6.6 IQR 1.8 versus 5.0 IQR 1.2; p
      = 0.000).Central augmentation index corrected to heart rate of 75 was significant
      higher in preeclamptic than normotensives women (23.4 +/- 12.4 versus 12.8 +/-
      12) with p < 0.002. Early-onset preeclampsia had significantly higher brachial
      diastolic blood pressure (87 IQR 79-101.5 versus 82 IQR 65-88; p = 0.0198) than
      late-onset preeclampsia. CONCLUSION: This study has demonstrated that women of
      rural Eastern Cape with preeclampsia have increased pulse wave velocity and
      peripheral augmentation index. This shows that preeclamptic women from rural
      Eastern Cape of South Africa have increased arterial stiffness.

PMID- 28448180
TI  - Renal denervation decreases blood pressure and renal tyrosine hydroxylase but
      does not augment the effect of hypotensive drugs.
AB  - The effect of renal denervation on the efficacy of antihypertensive drugs has not
      yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated
      with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal
      denervation or a sham procedure. Acute hemodynamic measurements were performed
      ten days later. Series showing a significant interaction between renal
      denervation and the drugs were repeated with chronic telemetry measurements. In
      the saline series, denervated rats showed a significantly lower mean arterial
      blood pressure (blood pressure) than the sham-operated rats. In contrast, in the
      metoprolol series denervated rats showed a significantly higher blood pressure
      than sham rats. There were no differences in blood pressure between denervated
      and sham rats in the losartan and indapamide series. In chronic studies, a 4-week
      treatment with metoprolol caused a decrease in blood pressure. Renal denervation
      and sham denervation performed 10 days after the onset of metoprolol treatment
      did not affect blood pressure. Denervated rats showed markedly reduced renal
      nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases
      blood pressure in hypertensive rats. The hypotensive action of metoprolol,
      indapamide, and losartan is not augmented by renal denervation, suggesting the
      absence of synergy between renal denervation and the drugs investigated in this
      study.

PMID- 28448181
TI  - Blood pressure control with cilnidipine treatment in Japanese post-stroke
      hypertensive patients: The CA-ATTEND study.
AB  - Blood pressure control is important in post-stroke hypertensive patients and
      antihypertensive treatment is recommended for such patients. Ca-channel blockers
      are recommended as the medications of choice for the treatment of post-stroke
      patients. Here, we report the results of a large-scale prospective post-marketing
      surveillance study of post-stroke hypertensive patients (n = 2667, male 60.4%,
      69.0 +/- 10.9 years) treated with cilnidipine, with regard to blood pressure
      control and adverse reactions. Cilnidipine treatment caused a decrease in both
      clinic and home blood pressures 2 months after the beginning of treatment, and
      the decreased blood pressure was maintained until the end of 12 months'
      observation. The proportion of patients in whom clinic blood pressure was well
      controlled (<140/90 mmHg) increased from 21.5% to 65.3% in cilnidipine treatment,
      with no differences in effectiveness among the various clinical subtypes of
      stroke. In total, 346 adverse events occurred, with an overall incidence of 8.9%
      (238 of 2667 patients). In the elderly group, specifically, a fall and a hip
      fracture each occurred in 1 (0.1%) patient. These results indicate that
      cilnidipine was effective in treating uncontrolled blood pressure and was well
      tolerated in Japanese post-stroke hypertensive patients in a real-world clinical
      setting.

PMID- 28448182
TI  - Estrogen receptor alpha XbaI GG genotype was associated with severe preeclampsia.
AB  - PURPOSE: Estrogen receptor-alpha (ERalpha) plays an essential role in the
      adaptation of increased uterine blood flow during gestation. Therefore, ERalpha
      gene could be a possible candidate for preeclampsia (PE) susceptibility. In
      current study we aimed to investigate the association of the ERalpha gene
      polymorphisms and PE in an Iranian population. METHODS: A total of 192 pregnant
      women with PE and 186 normotensive women were genotyped for ERalpha gene (PvuII
      and XbaI) polymorphisms by polymerase chain reaction-restriction fragment length
      polymorphism method. RESULTS: The frequencies of alleles and genotypes of ERalpha
      PvuII and XbaI polymorphisms were not different between PE and normotensive
      control women. However, higher frequency of GG genotype was observed in women
      with severe PE compared to mild PE (OR, 1.8 [95% CI, 1.1 to 3]; p = 0.02) and in
      severe PE compared to normotensive women [OR = 1.8 (1.1-3), p = 0.02] after
      adjusting for age, ethnicity, and primiparity. CONCLUSIONS: The GG genotype of
      ERalpha XbaI polymorphism could be a genetic risk factor for PE predisposition.

PMID- 28448183
TI  - Age-related change in contribution of stroke volume to central pulse pressure.
AB  - We investigated age-related change in the contribution of stroke volume (SV) to
      central PP (cPP). Eighty seven adult subjects who were free of vasoactive agents
      were included. Subjects were divided into three age groups: young (20-39 years, n
      = 26), middle (40-49 years, n = 29), and old (>=50 years, n = 32). SV was
      calculated by Doppler echocardiography. Hemodynamic indices were measured using a
      brachial cuff-based oscillometric method. The brachial and cPP showed a small
      decline from the young group to the middle group and a greater rise after 50
      years old. SV significantly and positively correlated with brachial (r = 0.53, p
      < 0.01) and cPP (r = 0.57, p < 0.01) in the young group. In the middle group, the
      association of SV with brachial pulse pressure was significant (r = 0.38, p =
      0.04) and that with cPP was bordering significant (r = 0.34, p = 0.07). No
      significant association was found between SV and PP in the old group. In
      conclusion, the contribution of SV to cPP decreases with age. Age-related changes
      in the determinants of cPP should be considered when investigating the clinical
      value of cPP.

PMID- 28448184
TI  - Erythropoietin mediates brain-vascular-kidney crosstalk and may be a treatment
      target for pulmonary and resistant essential hypertension.
AB  - Organ crosstalk pathways represent the next frontier for target-mining in
      molecular medicine for existing syndromes. Pulmonary hypertension and resistant
      essential hypertension are syndromes that have been proven elusive in etiology,
      and frequently refractory to first-line management. Underlying crosstalk
      mechanisms, not yet considered in these treatments, may hinder outcomes or unlock
      novel treatments. This review focuses systematically on erythropoietin, a
      synthesizable molecule, as a mediator of brain-kidney crosstalk. Insights gained
      from this review will be applied to cardiovascular diseases in a clinician
      directed fashion.

PMID- 28448185
TI  - Addition of spironolactone in patients with resistant hypertension: A meta
      analysis of randomized controlled trials.
AB  - This study was designed to assess the effect of additional spironolactone on
      blood pressure in patients with resistant hypertension. MEDLINE, EMBASE, and
      Cochrane Library were searched to identify randomized controlled trials (RCTs)
      that determined the effect of add-on spironolactone on blood pressure in patients
      with resistant hypertension compared with a control group. A total of five RCTs
      met the inclusion criteria. Spironolactone reduced office systolic blood pressure
      (SBP) by 15.73 mmHg (95% CI -20.45 to -11.0; P < 0.00001) and office diastolic
      blood pressure (DBP) by 6.21 mmHg (95% CI -8.33 to -4.1, P < 0.00001) as compared
      to placebo group. The pooled changes of 24 h ambulatory or home SBP and DBP were 
      8.7 mmHg (95% CI -8.79 to -8.62, P < 0.00001) and -4.12 mmHg (95% CI -4.48 to 
      3.75, P < 0.00001), in favor of the spironolactone group. In comparison with
      alternative drugs including beta-blocker, candesartan, or alpha methyldopa,
      spironolactone reduced home SBP by 4.5 mmHg (95% CI -4.63 to -4.37, P < 0.00001).
      Addition of spironolactone provides benefit effect on blood pressure in patients
      with resistant hypertension.

PMID- 28448186
TI  - Association between CYP3A5 genotypes with hypertension in Chinese Han population:
      A case-control study.
AB  - BACKGROUND: The association of CYP3A5 gene polymorphisms with hypertension in the
      Chinese population is unknown. We explored the association between the CYP3A5
      (rs776746) gene and hypertension in the Chinese Han population. METHODS: Using a
      case-control design, 340 cases and 254 controls were enrolled from the Third
      Affiliated Hospital of South Medical University between July and December of
      2015. We used a standardized questionnaire to collect data regarding age, sex,
      smoking, drinking, family history of hypertension, and physical exercise. Height
      and weight were measured, and the body mass index (BMI) was calculated by
      weight/height2. Blood pressure was measured three times after 5 min of rest with
      at least 15 s between measurements, and the mean was considered the final BP. A
      Clinical examination was conducted. RESULTS: A total of 594 participants,
      including 340 cases and 254 controls, were entered into the analyses. The
      genotype frequencies of the CYP3A5 G>A polymorphism did not deviate from the
      Hardy-Weinberg equilibrium. The genotype frequencies among the cases were 38.8%
      (GA, 132 individuals), 42.9% (GG, 146 individuals), and 18.2% (AA, 62
      individuals). The differences in genotype between the cases and the controls were
      statistically significant. The AA genotype was associated with an elevated risk
      of hypertension after adjusting for potential confounders in Model 2. There was
      no interaction between smoking and the CYP3A5 genotype, while the interaction
      between drinking and the CYP3A5 genotype was significant. CONCLUSION: The CYP3A5
      gene may be associated with the risk of hypertension in the Chinese Han
      population, and this effect may be exacerbated by drinking.

PMID- 28448187
TI  - Self-reported adherence to therapeutic regimens among patients with hypertension.
AB  - OBJECTIVES: To assess Jordanian hypertensive patients' adherence rate to
      hypertension therapeutic regimen (HTR) and to identify the strongest predictors
      of adherence rate among such patients. DESIGN AND SAMPLE: A descriptive
      comparison design and convenience sampling were used. The sample comprised 192
      participants who came to their regular appointments in a public healthcare
      center. MEASUREMENT: The Hill-Bone Compliance to High Blood Pressure Therapy
      Scale and the Hypertension Knowledge-Level Scale were used to assess adherence to
      HTR and knowledge of hypertension, respectively. RESULTS: The mean total score
      for adherence to HTR was 87.3, and 82.8% of participants reported good adherence
      overall. Adherence scores were significantly higher among women, less educated,
      unemployed participants, those with comorbidities, those with a negative family
      history of hypertension, and those who visited their physicians regularly. To
      identify the most significant predictors of adherence to HTR, multiple linear
      regression analysis was performed. Results indicated that good adherence to HTR
      was predicted by greater knowledge about hypertension and regularly visiting a
      physician. CONCLUSIONS: Adherence to taking antihypertensive medications was good
      overall among the study participants; these participants, however, were less
      interested in adherence to reduced sodium intake and keeping up with medical
      appointments. Hypertensive patients appear to follow instructions related to
      pharmacological management and are less likely to comply with other elements of
      HTR.

PMID- 28448188
TI  - Effects of indomethacin on prostanoid synthesis and vasomotor responsiveness in
      endothelium-denuded abdominal and thoracic aortas of Wistar rats.
AB  - In endothelium-denuded abdominal (but not thoracic) aortas of rats, the
      nonselective cyclooxygenase (COX) inhibitor, indomethacin, suppressed
      contractions evoked by alpha-adrenergic agonists hypothetically mediated by
      prostanoids. We aimed to identify these non-endothelial-derived contractile
      prostanoids released by alpha-adrenergic receptors activation. Endothelium
      denuded abdominal and thoracic aortas of Wistar rats were used for biochemical
      and functional analyses. Western blot analysis showed that COX-1 and COX-2
      protein levels were respectively equivalent in endothelium-denuded abdominal and
      thoracic aortas. Enzyme immunoassay data supported direct evidence of
      phenylephrine-stimulated release of prostanoids (PGI2, PGE2, and PGF2alpha) by
      thoracic and abdominal aortas without endothelium, and their almost complete
      inhibition by 1 MUM indomethacin. Isometric force measurements established that
      10 MUM indomethacin-but no lower concentrations-inhibited the contractions evoked
      by phenylephrine in endothelium-denuded abdominal aorta. In this preparation, 10
      MUM indomethacin also depressed the contractions provoked by angiotensin II and
      high K+ (80 mM). In fact, indomethacin (up to 1 mM) caused concentration
      dependent reductions in all abovementioned contractile responses. In endothelium
      denuded thoracic aortas, however, only 1 mM indomethacin significantly depressed
      the contractile activity stimulated by either phenylephrine, angiotensin II, or
      high K+. Hence, there was a clear quantitative difference in response to
      indomethacin between abdominal and thoracic aortas without endothelium.
      Altogether, the results indicate that prostanoids induced by phenylephrine in
      abdominal and thoracic aortas were derived from non-endothelial COX-mediated
      metabolism; notably, the decrease in prostanoid synthesis could not account for
      the inhibition of vasoconstrictor responses by indomethacin: Through COX
      independent actions, indomethacin inhibited aortic smooth muscle contractility.

PMID- 28448189
TI  - Effect of antihypertensive treatment on the long-term outcome of patients
      discharged after acute ischemic stroke.
AB  - We aimed to evaluate the effects of the five main classes of antihypertensive
      agents on the long-term outcome of 313 consecutive patients discharged after
      acute ischemic stroke (36.4% males, age 78.5 +/- 6.3 years). One year after
      discharge, the functional status [evaluated with the modified Rankin scale
      (mRS)], the occurrence of cardiovascular events, and vital status were recorded.
      Patients prescribed angiotensin receptor blockers (ARBs) had lower mRS than
      patients not prescribed ARBs (1.7 +/- 2.0 vs. 2.9 +/- 2.5, respectively; p =
      0.006). The rates of adverse outcome (mRS 2-6) and cardiovascular events did not
      differ between patients prescribed each one of the major classes of
      antihypertensive agents and those not prescribed the respective class. Patients
      who were prescribed ARBs had lower risk of death during follow-up than patients
      who did not receive ARBs (9.4 and 26.9%, respectively; p < 0.05). In binary
      logistic regression analysis, the only independent predictor of all-cause
      mortality during follow-up was the mRS at discharge (relative risk 1.69, 95%
      confidence interval 1.25-2.28; p < 0.001). In conclusion, in patients discharged
      after acute ischemic stroke, administration of ARBs appears to have a more
      beneficial effect on long-term functional outcome and all-cause mortality than
      treatment with other classes of antihypertensive agents.

PMID- 28448190
TI  - Leptin is associated with heart rate recovery in Chinese hypertensive patients.
AB  - Elevated serum leptin concentrations are closely related to sympathetic nervous
      system activation in essential hypertension (EH); however, it is not clear
      whether or not they are associated with parasympathetic nervous system impairment
      in EH. Heart rate recovery (HRR) is a reproducible method used to assess
      parasympathetic activity. This study aimed to investigate the relationship
      between serum leptin and HRR in Chinese untreated EH patients. This was a cross
      sectional study enrolling 471 Chinese EH patients (205 men, 266 women; mean age
      63.1 years). HRR was calculated during an incremental cardiopulmonary exercise
      test. Simple and multiple regression analyses were used to assess the correlation
      between serum leptin level and HRR value. Serum leptin levels elevated with
      increasing BP values. Moreover, univariate analysis revealed that the HRR value
      was negatively correlated with serum leptin (r = -0.037, P < 0.01). In multiple
      regression analysis, the age-adjusted serum leptin level was negatively
      correlated with HRR (beta = -0.268, P < 0.01). Serum leptin remained negatively
      associated with HRR (beta = -0.017, P < 0.01) after further adjustments for
      factors including age, systolic blood pressure, total cholesterol, and several
      factors that correlated with HRR. Our findings demonstrated that a raised serum
      leptin concentration is related to HRR blunt, which suggests that the role of
      leptin in the development of EH might be associated with impairment of the
      parasympathetic nervous system as well.

PMID- 28448191
TI  - Total arterial compliance, estimated by a novel method, is better related to left
      ventricular mass compared to aortic pulse wave velocity: The SAFAR study.
AB  - AIM: The investigation of the association between total arterial compliance (CT)
      estimated by a novel technique-with left ventricular mass (LVM) and hypertrophy
      (LVH). Our hypothesis was that CT may be better related to LVM compared to the
      gold-standard regional aortic stiffness. Within the frame of the ongoing cross
      sectional study "SAFAR," 226 subjects with established hypertension or with
      suspected hypertension underwent blood pressure (BP) assessment, carotid-to
      femoral pulse wave velocity (cf-PWV), and echocardiographic measurement of LVM.
      LVM index (LVMI) was calculated by the ratio of LVM to body surface area. CT was
      estimated by a previously proposed and validated formula: CT = 36.7 /cf-PWV2
      [ml/mmHg]. LVMI was related to age (r = 0.207, p = 0.002), systolic BP (r =
      0.248, p < 0.001), diastolic BP (r = 0.139, p = 0.04), mean BP (r = 0.212, p =
      0.002), pulse pressure (r = 0.212, p = 0.002), heart rate (r = -0.172, p =
      0.011), cf-PWV (r = 0.268, p < 0.001), and CT (r = -0.317, p < 0.001). The
      highest correlation was observed for CT that was significantly stronger than the
      respective correlation of cf-PWV (p < 0.001). In multivariate analysis, CT was a
      stronger determinant, compared to cf-PWV, of LVMI and LVH. It remains to be
      further explored whether CT has also a superior prognostic value beyond and above
      local or regional (segmental) estimates of pulse wave velocity.

PMID- 28448192
TI  - Epidemiology of newly diagnosed hypertensives in a tertiary care hospital in a
      developing country.
AB  - BACKGROUND: Cardiovascular diseases are the main cause of death in most countries
      and the past two decades have shown a global increase. Hypertension (HTN) was
      found to be the leading risk factor in 2010 as qualified by Disability Adjusted
      Life Years. Epidemiological studies in this regard in Sri Lanka are scarce. Thus,
      describing epidemiological patterns of HTN in the Sri Lankan population will help
      policy makers in planning preventive healthcare programs and aid in preparing
      strategies to cope with the increasing demand for healthcare facilities. METHODS:
      This is a cross-sectional descriptive study conducted at the Teaching Hospital
      Peradeniya, Sri Lanka, among newly diagnosed hypertensives according to the JNC 7
      report, attending the hypertensive clinic through referral. Data were collected
      by an interviewer administered structured questionnaire, and epidemiological
      patterns were analyzed. RESULTS: Among 244 newly diagnosed hypertensives, the
      mean age was 58.3 years (SD = 12.3) and the majority were females. 66.8% had
      stage 2 HTN (>160 mmHg) at the time of first presentation to a tertiary care
      center. There was no statistically significant difference of the stage of HTN
      based on sex, education level, occupation, marital status, consumption of
      alcohol, and smoking. CONCLUSION: Majority of the population had very high blood
      pressure at first diagnosis, indicating delay in the detection of HTN at an early
      stage. Therefore, measures to increase the probability of early detection of HTN
      will be useful in reducing morbidity and mortality associated with HTN.

PMID- 28448193
TI  - Safety and effectiveness of etanercept for treatment of juvenile idiopathic
      arthritis: Results from a postmarketing surveillance.
AB  - OBJECTIVES: The objectives of this surveillance were to determine safety and
      effectiveness of etanercept in patients with juvenile idiopathic arthritis (JIA).
      METHODS: In this postmarketing surveillance, patients aged 5-16 years with active
      polyarthritis JIA were treated with etanercept at the doses approved in the
      Japanese package insert. The occurrence and seriousness of adverse events (AEs)
      were assessed using the Japanese Medical Dictionary for Regulatory Activities
      version 15.1. Effectiveness was determined as the improvement from baseline in
      disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR),
      remission, and physician's assessment of overall improvement. The number of
      responders was expressed as a percentage. The last observation carried forward
      method was used to impute missing data. RESULTS: Safety analysis included 102
      patients; 22 patients experienced 36 treatment-related AEs, three of which were
      unexpected. None of the AEs were deemed to need special safety warnings.
      Effectiveness analysis included 87 patients. At 24 weeks, 29/46 (63.0%) patients
      demonstrated either good or moderate response in DAS28-4/ESR and treatment was
      assessed to be markedly effective or effective by physicians in 79/83 (95.2%)
      patients. CONCLUSIONS: These data are consistent with earlier reports showing
      that etanercept was effective and demonstrated no safety signals in patients with
      JIA.

PMID- 28448194
TI  - Co-Administration of an Excipient Oligonucleotide Helps Delineate Pathways of
      Productive and Nonproductive Uptake of Phosphorothioate Antisense
      Oligonucleotides in the Liver.
AB  - Phosphorothioate (PS) modified antisense oligonucleotides (ASOs) have progressed
      rapidly in the clinic for treating a variety of disease indications. We
      previously demonstrated that the activity of PS ASOs in the liver can be enhanced
      by co-infusion of an excipient oligonucleotide (EON). It was posited that the EON
      saturates a nonproductive uptake pathway(s) thereby permitting accumulation of
      the PS ASO in a productive tissue compartment. In this report, we measured PS ASO
      activity following administration by bolus, infusion or co-fusion with EON within
      hepatocytes and nonparenchymal cells (NPCs), of the liver. This revealed that
      while ASOs accumulate preferentially in NPCs, they are intrinsically more active
      in hepatocytes. Furthermore, we show that the EON enhances ASO potency when
      infused up to 72 h before or after administration of the active ASO suggesting
      that the EON can saturate and displace the ASO from nonproductive to productive
      compartments. Physical presence of the EON in tissues was required for optimal
      potentiation suggesting that there is a dynamic distribution of the ASO and EON
      between the compartments. Lastly, using a candidate approach, we confirmed
      Stabilin-2 as a molecular pathway for ASO uptake in sinusoidal endothelial cells
      and the ASGR as a pathway for ASO uptake into hepatocytes in the liver.

PMID- 28448195
TI  - Design characteristics of the Corrona Japan rheumatoid arthritis registry.
AB  - OBJECTIVES: The primary objective is to prospectively study the comparative
      safety and effectiveness of older and newer classes of nonbiologic DMARDs
      (Disease-modifying antirheumatic drugs), biologic DMARDs and targeted synthetic
      therapies approved for rheumatoid arthritis (RA) in a real-world patient
      population in Japan. METHODS: Prospective, multicenter, noninterventional,
      observational study across geographic distribution of both private and public
      institutions for patients with RA who are newly prescribed one of the following
      medications: (1) methotrexate; (2) anti-TNF biologic DMARDs; (3) non-TNF biologic
      DMARDs; and (4) approved JAK inhibitors at the time of enrollment into the
      registry. Target enrollment is currently 2000 subjects. Baseline and follow-up
      data on patient demographics, medical history, disease activity, laboratory
      results, comorbidities, hospitalizations, and targeted safety events are obtained
      via Physician and Patient Questionnaires. RESULTS: Fifty sites are anticipated to
      participate with 40 sites ethics committee (EC) approved at the time of
      submission consisting of 23% clinics, 21% private academic hospitals, 29% private
      mid-sized to large hospitals, 15% national academic hospitals, and 12% national
      hospitals. CONCLUSION: The Corrona Japan RA Registry will provide real-world
      evidence from both private and public institutions on the comparative
      effectiveness and safety of recently approved RA therapies in Japan.

PMID- 28448196
TI  - Subcellular compartmentation of 4-aminobutyrate (GABA) metabolism in arabidopsis:
      An update.
AB  - This addendum discusses the compartmentation of gamma-aminobutyrate (GABA)
      metabolism, highlighting recent progress with Arabidopsis thaliana and raising
      new questions about the roles of mitochondria, plastids and peroxisomes in
      abiotic stress tolerance.

PMID- 28448197
TI  - Surgical Site Infections and Associated Operative Characteristics.
AB  - Surgical site infection (SSI) contributes significantly to surgical morbidity.
      Patient factors and operative factors contribute to the risk of development of
      SSI. This review focuses on understanding operative characteristics that are
      associated with an increased risk of SSI. Much attention has been given to
      protocol care to reduce SSI, such as hair removal, skin preparation, and pre
      operative antibiotic agents. Even with this, the appropriate antibiotic and re
      dosing regimens often remain a challenge. Other operative factors such as blood
      loss/transfusion, emergency/urgent cases, duration of the operation, type of
      anesthesia, and resident involvement are also potentially modifiable to reduce
      the risk of SSI. Data are reviewed to highlight the increased risk associated
      with such factors. Strategies to reduce risk, such as operative care bundles,
      have significant promise to reduce the incidence of SSI for any given procedure.

PMID- 28448198
TI  - Boronic acids as tools to study (plant) developmental processes?
AB  - Boron (B) is an essential micronutrient for organisms. In plants, B is known to
      stabilize the cell wall by crosslinking Rhamnogalacturonan II through ester bonds
      formed with cis-diols of sugar moieties. However, B is believed to be required
      for additional functions such as stability and function of (plasma membrane)
      proteins involved in signal transduction pathways. We have recently shown that
      boronic acids, competitors of B, efficiently induce perfect phenocopies of
      monopteros mutants. This effect is enigmatic because like B, boronic acids should
      find numerous cellular targets and thus disturb many biologic processes ending in
      a spectrum of unspecific embryo phenotypes. Based on chemical characteristics of
      boronic acids and their derivatives we discuss reasons that could explain this
      unusual specificity. The peculiarities of this class of compounds could provide
      new tools for studying developmental processes.

PMID- 28448199
TI  - Deferiprone for the treatment of transfusional iron overload in thalassemia.
AB  - INTRODUCTION: Transfusional iron overload can lead to hepatic fibrosis,
      arrhythmias and congestive heart failure and a number of endocrinopathies.
      Deferiprone is an oral iron chelator approved for use in the United States as a
      second line agent for the treatment of transfusional iron overload in patients
      with thalassemia. Areas covered: This article will review the data regarding the
      efficacy of deferiprone for iron chelation and prevention and reversal of iron
      related complications, the drug's adverse effect profile, and the use of this
      drug in combination regimens. Expert commentary: Extensive data support that
      deferiprone is particularly efficacious at cardiac iron removal and therefore, a
      chelator regimen that contains deferiprone is generally recommended when there is
      significant cardiac iron loading and/or in the setting of iron-related cardiac
      disease. The most concerning side effects of deferiprone are agranulocytosis and
      milder forms of neutropenia, which require appropriate monitoring and
      patient/provider education.

PMID- 28448200
TI  - Better Together: The Making and Maturation of the Palliative Care Research
      Cooperative Group.
AB  - OBJECTIVE: To describe the growth and outcomes of the Palliative Care Research
      Cooperative Group (PCRC). BACKGROUND: Despite advances, significant gaps remain
      in the evidence base to inform care for people with serious illness. To generate
      this needed evidence and bolster research capacity, the Palliative Care Research
      Cooperative (PCRC) group was formed. METHODS: The PCRC supports investigators in
      the conduct of multisite clinical studies. After developing a governance
      structure and completing a proof of concept demonstration study, the PCRC
      expanded its infrastructure to include additional resource cores (Clinical
      Studies; Measurement; Data Informatics and Statistics; and Caregiver Studies).
      The PCRC also supports an Investigator Development Center as many palliative care
      investigators valued opportunities to advance their skills. Additional key
      aspects of PCRC resources include a Scientific Review Committee, a Publications
      Committee, and initiatives to purposefully engage investigators in a community of
      palliative care science. RESULTS: The PCRC has grown to over 300 members
      representing more than 130 distinct sites. To date, the PCRC has supported the
      submission of 51 research applications and has engaged in 27 studies. The PCRC
      supports investigator research development needs through webinars and clinical
      trials "intensives." To foster a sense of community, the PCRC has convened
      biannual meetings, developed special interest groups, and regularly communicates
      via a newsletter and its website. CONCLUSION: With a particular focus on
      facilitating conduct of rigorous multisite clinical studies, the PCRC fosters an
      engaged multidisciplinary research community, filling an important void in
      generating and disseminating evidence that informs the provision of high-quality
      care to people with serious illness.

PMID- 28448201
TI  - Cellular polyamines modulate mRNA stability.
AB  - Polyamines (PAs) are polycationic compounds found in all living organisms and
      play crucial roles in growth and survival. PAs interact with and modulate the
      functions of anionic macromolecules such as DNA, RNA and proteins. LHR1/PUT3 is a
      polyamine influx transporter localized in the plasma membrane in Arabidopsis. In
      our recent paper in The Plant Journal, 1 we demonstrated that LHR1/PUT3 has a
      pivotal role in stabilizing the mRNAs of several important heat stress responsive
      genes under high temperature. In this short communication, we discuss about a
      putative pathway for modulating the PUT3 transport activity and the significance
      of evolutionary variations in PUT3 in Arabidopsis.

PMID- 28448202
TI  - Current progress in orchid flowering/flower development research.
AB  - Genetic pathways relevant to flowering of Arabidopsis are under the control of
      environmental cues such as day length and temperatures, and endogenous signals
      including phytohormones and developmental aging. However, genes and even
      regulatory pathways for flowering identified in crops show divergence from those
      of Arabidopsis and often do not have functional equivalents to Arabidopsis and/or
      existing species- or genus-specific regulators and show modified or novel
      pathways. Orchids are the largest, most highly evolved flowering plants, and form
      an extremely peculiar group of plants. Here, we briefly summarize the flowering
      pathways of Arabidopsis, rice and wheat and present them alongside recent
      discoveries/progress in orchid flowering and flower developmental processes
      including our transgenic Phalaenopsis orchids for LEAFY overexpression. Potential
      biotechnological applications in flowering/flower development of orchids with
      potential target genes are also discussed from an interactional and/or
      comparative viewpoint.

PMID- 28448203
TI  - Systematic Review and Meta-Analysis of Randomized Controlled Trials Evaluating
      Prophylactic Intra-Operative Wound Irrigation for the Prevention of Surgical Site
      Infections.
AB  - BACKGROUND: Surgical site infections (SSIs) are one of the most common hospital
      acquired infections. To reduce SSIs, prophylactic intra-operative wound
      irrigation (pIOWI) has been advocated, although the results to date are
      equivocal. To develop recommendations for the new World Health Organization (WHO)
      SSI prevention guidelines, a systematic literature review and a meta-analysis
      were conducted on the effectiveness of pIOWI using different agents as a means of
      reducing SSI. METHODS: The PUBMED, Embase, CENTRAL, CINAHL, and WHO databases
      were searched. Randomized controlled trials (RCTs) comparing either pIOWI with no
      pIOWI or with pIOWI using different solutions and techniques were retrieved with
      SSI as the primary outcome. Meta-analyses were performed, and odds ratios (OR)
      and the mean difference with 95% confidence intervals (CI) were extracted and
      pooled with a random effects model. RESULTS: Twenty-one studies were suitable for
      analysis, and a distinction was made between intra-peritoneal, mediastinal, and
      incisional wound irrigation. A low quality of evidence demonstrated a
      statistically significant benefit for incisional wound irrigation with an aqueous
      povidone-iodine (PVP-I) solution in clean and clean contaminated wounds (OR 0.31;
      95% CI 0.13-0.73; p = 0.007); 50 fewer SSIs per 1,000 procedures (from 19 fewer
      to 64 fewer)). Antibiotic irrigation had no significant effect in reducing SSIs
      (OR 1.16; 95% CI 0.64-2.12; p = 0.63). CONCLUSION: Low-quality evidence suggests
      considering the use of prophylactic incisional wound irrigation to prevent SSI
      with an aqueous povidone-iodine solution. Antibiotic irrigation does not show a
      benefit and therefore is discouraged.

PMID- 28448204
TI  - Future Research Opportunities in Peri-Prosthetic Joint Infection Prevention.
AB  - Peri-prosthetic joint infection (PJI) is a serious complication of prosthetic
      joint arthroplasty. A better understanding and reversal of modifiable risk
      factors may lead to a reduction in the incidence of incisional (superficial and
      deep) and organ/space (e.g., PJI) surgical site infections (SSI). Recently, the
      Centers for Disease Control and Prevention (CDC) and the Healthcare Infection
      Control Practices Advisory Committee (HICPAC) published the Guideline for
      Prevention of Surgical Site Infection. This targeted update applies evidence
      based methodology in drafting recommendations for potential strategies to reduce
      the risk of SSI both across surgical procedures and specifically in prosthetic
      joint arthroplasty. A panel of PJI content experts identified nine PJI prevention
      research opportunities based on both evidence gaps identified through the
      guideline development process (transfusion, immunosuppressive therapy,
      anticoagulation, orthopedic space suit, and biofilm) and expert opinion
      (anesthesia, operative room environment, glycemic control, and Staphylococcus
      aureus nasal screening and decolonization. This article offers a road map for PJI
      prevention research.

PMID- 28448205
TI  - Practicing maternal virtues prematurely: The phenomenology of maternal identity
      in medically high-risk pregnancy.
AB  - In this study, we examine the phenomenology of maternal identity development
      among U.S. women hospitalized with medically high-risk pregnancies (MHRP). We
      conducted 16 in-depth interviews with women and found that they drew on
      culturally normative notions of maternal nurture, worry, and sacrifice to
      construct maternal identity in the context of MHRP. Based on our findings, we
      suggest that MHRP shape women's sense of connection to and distinctive cognitive
      representations of their fetus. We conclude that hospitalization simultaneously
      promotes and challenges women's early maternal identifications.

PMID- 28448206
TI  - Mycoplasma pulmonis of Rodents as a Possible Human Pathogen.
AB  - Mycoplasma pulmonis is a naturally occurring respiratory pathogen in rodents. To
      date, this pathogen was not isolated from humans. This study aimed to evaluate
      the prevalence and seropositivity to M. pulmonis in humans who have had direct
      contact with rats. Moreover, the prevalence of M. pulmonis in pet and laboratory
      rats was assessed. Overall, 131 and 235 oropharyngeal swab samples were collected
      from human individuals and rats, respectively. In humans, M. pulmonis was
      detected by PCR in 21 of 86 pet rat keepers (24.42%), 10 of 13 technicians
      (76.32%), and 8 of 32 (25.0%) veterinarians. In rats, M. pulmonis was identified
      by PCR in 86 of 122 pet rats (70.49%) and 56 of 113 (49.56%) laboratory rats.
      Seroprevalence in humans was examined by screening sera from 44 individuals for
      M. pulmonis-specific IgG using ELISA. In total, 26 out of 44 (59.09%) humans were
      seropositive to M. pulmonis (4 out of 9 technicians, 8 of 12 veterinarians, and
      15 of 23 pet rat keepers).The high antibody titer was found in 4 individuals (2
      pet rat keepers and 2 veterinarians), whereas the moderate and low antibody
      titers were found in 8 and 14 individuals, respectively. The high antibody titer
      found in humans might indicate an active infection. However, it is unknown
      whether the presence of M. pulmonis in humans might be associated with disease
      and whether the foreign Mycoplasma can survive for long in its new environment.

PMID- 28448208
TI  - Explanations for Not Receiving the Seasonal Influenza Vaccine: An Ontario Canada
      Based Survey.
AB  - Despite evidence of the importance of the seasonal influenza vaccine for both
      individual and population health, only a third of the Ontario population received
      the vaccine in 2013/2014. The objective of this study was to identify why
      Ontarians are not getting the seasonal influenza vaccine. Written responses to
      the question "Why didn't you get the seasonal flu vaccine in the last flu
      season?" were deductively analyzed using the Conceptual Model of Vaccine
      Hesitancy. Inductive coding was also conducted to identify explanations that fall
      outside of the present model and may be unique to the seasonal influenza vaccine.
      Data were collected between August and early September, 2014 through a survey in
      the Region of Waterloo, Ontario. Overall, 91.4% of responses could be explained
      using the conceptual model and specifically relate to perceived importance of
      vaccination (46.8%), moral convictions (19.4%), and past experiences with
      vaccinations services (14.5%). Notably, explanations related to healthcare
      professional attitudes, risk perceptions and trust, and subjective norms were
      identified to a much lesser extent than those discussed above. The remaining 8.6%
      of responses cannot be explained by the model because they do not relate to
      hesitancy. Our data contribute to the minimal body of Canadian research
      investigating low uptake of the seasonal flu vaccine, adding to an evidence-base
      upon which to inform promotional campaigns. Our data also highlight the utility
      of the Conceptual Model of Vaccine Hesitancy for the design and analysis of
      research investigating seasonal flu vaccine refusal or delay.

PMID- 28448207
TI  - Gender differences in endovascular treatment of infrainguinal peripheral artery
      disease.
AB  - BACKGROUND: Despite ongoing research concerning comorbidities and clinical
      presentation of peripheral arterial disease (PAD), the issue of gender associated
      differences in treatment is far from being settled. PATIENTS AND METHODS: This
      was a prospective, non-randomized multicentre study design. All patients
      suffering from intermittent claudication (IC) or critical limb ischaemia (CLI)
      were included. RESULTS: A total of 2,798 procedures for symptomatic PAD in the
      infrainguinal region were recorded, with 1,696 (61.4 %) males. Distribution of
      comorbidities for patients with IC were gender-specifically different. Smoking
      was more common in men (41.9 vs. 31.9 %, p < .001), men had more often previous
      coronary heart disease (35.2 vs. 27.7 %, p = .007), and suffered more often from
      diabetes (33.9 vs. 28.2 %, p = .037). Women were generally older (71 vs. 77
      years). Men were more prone to present with IC (46.9 vs. 43.6 %, p < .001) and
      ulcer/gangrene (43.6 vs. 41.2 %, p < .001). Women were more likely to present
      with rest pain (9.5 vs. 15.1 %, p < .001). Men were more often treated for a
      lesion below the knee (BTK) (21.1 vs. 14.9 %, p < .001), and females above the
      knee (ATK) (58.1 vs. 61.5 %, p < .001). Logistic regression analysis revealed a
      significant association of male gender and treatment for lesions BTK (OR 1.565,
      95 % CI 1.281-1.913, p < .001). Dissections and bleeding complications were more
      often observed in females with IC (3.3 vs. 7.2 %, p = 0.003; 0.4 vs. 1.5 %, p =
      0.044). Women were rather discharged to rehabilitation and had a longer hospital
      stay compared to men (3.4 vs. 8.9 %, p < .001; three vs. four days, p = .023).
      CONCLUSIONS: The present study provides an overview on gender-specific
      differences in endovascular treatment of PAD. To date, available evidence on this
      topic is limited, emphasising the importance of further vascular research
      targeting this topic.

PMID- 28448209
TI  - Solution-focused brief therapy for Chilean primary care patients: Exploring a
      linguistic adaptation.
AB  - Solution-focused brief therapy (SFBT) is a resource-based, future-oriented
      therapeutic approach that focuses on finding exceptions to problems and
      identifying coping strategies to build solutions. SFBT has been efficacious with
      individuals with alcohol use disorders. Chile experiences high levels of alcohol
      consumption and alcohol-related health consequences. Despite the international
      dissemination of SFBT, this is the first study to attempt a linguistic adaptation
      of SFBT in a Latin American country. We conducted 9 cognitive interviews to
      examine 13 translated main SFBT tools and 3 focus groups to gather information on
      cultural aspects of alcohol use in primary care. Results suggest that Chileans
      understood most SFBT tools, albeit with some linguistic modifications of original
      translations, and that family, gender, and meaningful issues should be considered
      when working with individuals with alcohol use disorders.

PMID- 28448210
TI  - Body composition and inflammatory markers in pubertal girls: Comparison between
      athletes and non-athletic controls.
AB  - Various inflammation parameters are increased with childhood obesity, but few
      comparable data are found in lean growing athletes. This study aims to
      characterize differences in 12 simultaneously measured inflammatory parameters
      between pubertal rhythmic gymnasts (RG) and untrained controls (UC), and to
      examine the relationship between body composition and inflammatory markers. Sixty
      10-12-year-old girls were divided into RG (n = 30) and UC (n = 30). Fat mass (FM)
      and fat free mass (FFM) were measured by dual-energy X-ray absorptiometry. Leptin
      and 12 inflammatory parameters (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10,
      vascular endothelial growth factor, interferon-gamma [IFN-gamma], tumor necrosis
      factor-alpha, IL-1alpha, IL-1beta, monocyte chemotactic protein-1 and epidermal
      growth factor) were measured from fasting blood samples. No differences were seen
      in 12 inflammatory markers between studied groups. As expected, leptin (RG: 2.4
      +/- 1.1; UC: 7.6 +/- 4.2 ng ml-1) and FM (RG: 7.3 +/- 2.3; UC: 11.8 +/- 5.1 kg)
      were lower (p < .05) in RG compared to UC. In the whole group of lean pubertal
      girls, 69.0% of the variability in body FM was determined by leptin, and 11.2% of
      the variability in body FFM was explained by IFN-gamma. In conclusion, measured
      12 inflammatory biomarkers were not different between RG and UC, despite lower
      leptin and FM in RG. In lean pubertal girls, IFN-gamma was independently
      associated with FFM, and leptin with FM.

PMID- 28448212
TI  - The Problem of Fertility 1936-1986.

PMID- 28448213
TI  - Birth Control Practice in Great Britain: A Review of the Evidence from Cross
      Sectional Surveys.

PMID- 28448211
TI  - Prevalence and Geographic Distribution of Vector-Borne Pathogens in Apparently
      Healthy Dogs in Croatia.
AB  - Vector-borne pathogens (VBPs) are a group of globally extended and quickly
      spreading pathogens that are transmitted by various arthropod vectors. The aim of
      the present study was to investigate the seroprevalence against Babesia canis,
      Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, Leishmania infantum,
      Dirofilaria immitis, and Ehrlichia canis in dogs in Croatia. We investigated 435
      randomly selected apparently healthy dogs in 13 different locations of Croatia
      for antibodies to B. canis by indirect immunofluorescence using a commercial IFA
      IgG Antibody Kit. All samples were also tested for qualitative detection of D.
      immitis antigen and for antibodies to A. phagocytophilum, B. burgdorferi sensu
      lato, L. infantum, and E. canis with two point-of-care assays. Overall, 112 dogs
      (25.74%, 95% confidence interval [CI] 21.70-30.12) were serologically positive
      for one or more of the pathogens. B. canis was the most prevalent pathogen
      (20.00%, 95% CI 16.34-24.07), followed by A. phagocytophilum (6.21%, 95% CI 4.12
      8.90), L. infantum, (1.38%, 95% CI 0.51-2.97), and B. burgdorferi sensu lato
      (0.69%, 95% CI 0.01-2.00). The lowest seroprevalence was for D. immitis and E.
      canis (0.46%, 95% CI 0.01-1.65). Coinfection was determined in 12 dogs (2.76%,
      95% CI 1.43-4.77), of which 10 were positive to two pathogens (7 with B. canis
      and A. phagocytophilum and 1 B. canis with B. burgdorferi sensu lato or L.
      infantum or E. canis). One dog was positive to three pathogens and another dog to
      four pathogens. Seroprevalence for babesia was age, breed, and lifestyle/use
      dependent. Purebred dogs had almost half the chance of developing disease than
      crossbred (OR = 0.58, p < 0.026, 95% CI 0.37-0.94). Seropositivity to B. canis
      was 3.41 times higher for dogs that lived outdoors/shelter (p < 0.006) or 4.57
      times higher in mixed/hunting (p < 0.001) compared to indoor/companion dogs. This
      is the first comprehensive survey of VBP seropositivity conducted in Croatia.
      Some of these VBPs are zoonotic and represent a potential risk to public health.

PMID- 28448214
TI  - Demographic Research in Britain 1936-1986.

PMID- 28448215
TI  - Emerging Issues in Demographic Research in the United States.

PMID- 28448216
TI  - Emerging Issues in Demographic Research for Contemporary Europe.

PMID- 28448217
TI  - Ageing: Age-Related Change in Later Life.

PMID- 28448218
TI  - Modelling Households: A Synthesis.

PMID- 28448219
TI  - Transitions in Young Adulthood in Great Britain.

PMID- 28448220
TI  - Unemployment: Family Circumstances and Childhood Correlates Among Young People in
      Britain.

PMID- 28448221
TI  - Fifty years on - Inequalities in Health.

PMID- 28448222
TI  - Patient experience and process measures of quality of care at home health
      agencies: Factors associated with high performance.
AB  - We examined the effects of provider characteristics on home health agency
      performance on patient experience of care (Home Health CAHPS) and process (OASIS)
      measures. Descriptive, multivariate, and factor analyses were used. While
      agencies score high on both domains, factor analyses showed that the underlying
      items represent separate constructs. Freestanding and Visiting Nurse Association
      agencies, higher number of home health aides per 100 episodes, and urban location
      were statistically significant predictors of lower performance. Lack of variation
      in composite measures potentially led to counterintuitive results for effects of
      organizational characteristics. This exploratory study showed the value of having
      separate quality domains.

PMID- 28448223
TI  - The ALERRT(r) instrument: a quantitative measure of the effort required to
      compromise prescription opioid abuse-deterrent tablets.
AB  - BACKGROUND: US FDA guidance recommends measuring the degree of effort needed to
      manipulate abuse-deterrent (AD) opioids. The ALERRT(r) instrument
      (PinneyAssociates; Bethesda, MD) uses visual analog scales to assess the labor,
      effort, and resources necessary to physically compromise AD product candidates in
      standardized settings. OBJECTIVE: Use the ALERRT(r) instrument for testing
      morphine abuse-deterrent, extended-release, injection-molded tablets (ADER-IMT)
      60 and 100 mg and the comparators immediate-release (IR) morphine sulfate 30 mg
      and extended-release (ER) morphine sulfate 60 mg. METHODS: Four technicians
      tested the products using 10 household tools. The ALERRT instrument quantified
      effort (all tools) and time (3 preselected tools) required for manipulation.
      RESULTS: Morphine-ADER-IMT 60 and 100 mg were difficult to manipulate, as
      demonstrated by high scores (mean range, 71.0-99.0 and 77.0-99.5, respectively).
      IR and ER morphine sulfate were easy to manipulate (low scores; mean range, 2.0
      14.8 and 2.3-17.5, respectively). Statistically significant mean differences
      between morphine-ADER-IMT and comparators' ALERRT scores were observed.
      Manipulations of morphine-ADER-IMT 60 and 100 mg for 300 seconds failed to
      produce substantial powdering. Manipulations of IR morphine sulfate (mean range,
      65.5-175.8 seconds) and ER morphine sulfate (49.3-163.0 seconds) produced
      substantial to complete powdering in 92% of tablets. CONCLUSIONS: Morphine-ADER
      IMT was extremely difficult to manipulate versus non-AD formulations of morphine.
      The ALERRT system differentiated the degree of effort for manipulation of
      morphine-ADER-IMT and non-AD morphine formulations, indicating sensitivity of
      this instrument as part of Category 1 testing. By measuring the degree of effort
      required for manipulation, the ALERRT instrument provides an empirical assessment
      into the relative difficulty of manipulating opioid analgesics for abuse.

PMID- 28448224
TI  - Patient Characteristics Associated with Inpatient Psychiatric Re-admissions and
      the Utility of the READMIT Clinical Risk Index.
AB  - In response to the problem of frequent 30-day readmissions to inpatient
      psychiatric facilities, Vigod and colleagues (2015) developed the READMIT
      clinical risk index to identify risk factors for psychiatric inpatient
      readmissions. The purpose of this descriptive retrospective study was to examine
      the effectiveness of the READMIT clinical risk index to identify patients that
      are at high risk for a 30-day inpatient psychiatric readmission at a state
      psychiatric hospital in the southeastern US. Data were extracted from the
      discharge summaries of patients discharged between September 2013 and December
      2014. Data collected included patient demographic variables (age, gender,
      race/ethnicity, primary diagnosis, housing status at discharge, employment, long
      acting injectable at discharge, substance abuse, education, and insurance status)
      and study variables from the READMIT clinical risk index (repeat admission,
      emergent admission, age, diagnosis and discharge, medical comorbidity, intensity,
      and time in hospital). The inclusion criterion was age 18 and above. There were
      no exclusion criteria. Findings indicated that age, insurance status, previous
      lifetime admissions, 'diagnoses and discharge' scores, and higher READMIT
      clinical risk index scores were associated with 30-day readmissions. Future
      research should include a prospective study of the READMIT clinical risk index to
      assess its predictability of 30-day readmissions and explore possible use of the
      minimum clinical risk index score to trigger evaluation of patient need for
      enhanced transitional care services posthospital discharge.

PMID- 28448225
TI  - Online Positive Thinking Training Intervention for Caregivers of Individuals with
      ASD: Necessity, Acceptability and Feasibility.
AB  - BACKGROUND: More than 3.5 million people in the United States are diagnosed with
      autism spectrum disorder (ASD). Caring for children with ASD can be stressful and
      can be detrimental to the well-being of the caregivers (CGs). However, the
      adverse effects of caregiving on the well-being of CGs may be avoided with
      appropriate interventions. CGs of persons with ASD might benefit from a positive
      thinking training (PTT) intervention to help them cope with the stress of
      caregiving. However, the necessity, acceptability and feasibility for PTT in ASD
      CGs have not been studied. OBJECTIVE: To examine the necessity, acceptability and
      feasibility of a six-week online PTT intervention designed to improve the well
      being of the CGs. DESIGN: Random assignment of ASD CGs to one of two conditions:
      (1) PTT online intervention or (2) Control group. RESULTS: The mean score on the
      depressive cognition scale (DCS) was 20, indicating a high need of PTT to all
      enrolled CGs. High depressive cognitions in ASD CGs were associated with lower
      positive thinking (r = -.39; p <.001). Regarding acceptability, CGs indicated
      that the different strategies and references to real life were the most
      interesting parts of the intervention. Regarding feasibility, CGs mentioned that
      listening to the voice-over PowerPoint and visualization was the easiest part of
      the PTT. CONCLUSIONS: Examination of the fidelity and effectiveness of the PTT
      are the next steps in the refinement of this intervention.

PMID- 28448227
TI  - Inspiration from ISPN.

PMID- 28448226
TI  - The Role of Social Support for Patients with Mental Disorders in Primary Care in
      Brazil.
AB  - The aim of this article was to identify the health care providers and other
      agencies in a given region where psychiatric patients included in the study
      reside. In addition, we evaluated how these patients perceive social support for
      specific needs related to mental health. This study was carried out using
      fieldwork and face-to-face semistructured interviews with 25 patients who were
      receiving psychiatric treatment through primary health care. We performed
      structural analysis of the data focusing on relationship structure. We identified
      that a significant number of health care providers were involved with the
      patients; however, some of them were ignored by patients interviewed.
      Participants cited mostly general practitioners, psychiatrists, and nurses, as
      professional references.

PMID- 28448228
TI  - Preliminary Psychometric Properties of the Verbal and Nonverbal Interaction
      Scale: An Observational Measure for Communication in Persons with Dementia.
AB  - Little attention has been given to sociable/unsociable communication in persons
      with dementia despite the importance of these behaviors in maintaining engagement
      in marital relationships. An observational measure of verbal and nonverbal
      communication in persons with dementia (Verbal and Nonverbal Interaction Scale
      CR) who were engaged in conversations with spouses was tested for reliability and
      validity. Married persons with dementia were video-recorded at home conversing
      with spouses over 10 weeks (N = 118 recordings). Reliability [inter-coder (.92),
      test-retest (r =.61-.77), internal consistency (alpha =.65 -.79)] were adequate.
      Following an intervention, the Verbal and Nonverbal Interaction Scale-CR
      predicted improved communication over 10 weeks. The ratio of sociable to
      unsociable communication improved by 4.46 points per session [beta = 4.46, t(10)
      = 1.96, p =.039]. VNVIS-CR is recommended to describe sociable and unsociable
      communication in persons with dementia as they engage in conversations with
      spouses.

PMID- 28448229
TI  - Breaking through the Glass Ceiling: Consumers in Mental Health Organisations'
      Hierarchies.
AB  - Contemporary mental health policies call for consumers to be engaged in all
      levels of mental health service planning, implementation, and delivery. Critical
      approaches to traditional healthcare hierarchies can effectively challenge
      barriers to better engagement with consumers in mental health organisations. This
      qualitative exploratory study analyses how particular strategies for consumer
      leadership facilitate or hinder relationships between consumers and mental health
      services, and how these strategies influence hierarchical structures. Fourteen
      participants from a range of mental health organisations were interviewed. These
      interviews were analysed using thematic analytic and discursive psychological
      techniques. The findings highlight several benefits of having consumers within
      mental health organisational hierarchies, and elaborate on ways that employees
      within mental health services can support integration of consumers into existing
      hierarchies. Specific barriers to consumers in hierarchies are discussed,
      including a lack of clarity of structures and roles within hierarchies, and
      resistance to consumers reaching the highest levels of leadership within
      organisations. Alternative hierarchical models which privilege consumers' control
      over resources and power are also discussed. Mental health organisations are
      encouraged to integrate consumer leaders into their hierarchical structures to
      improve their organisational offerings, their reputation, and their service
      innovation.

PMID- 28448230
TI  - Recovery-oriented Care and Leadership in Mental Health Nursing.

PMID- 28448231
TI  - Can Completing a Mental Health Nursing Course Change Students' Attitudes?
AB  - Nursing program graduates rarely choose mental health nursing as a career. A
      quasi-experimental study was conducted to examine attitudes of 310 nursing
      students towards persons with mental illness. Students completed surveys on the
      first and last days of their program's psychiatric mental health nursing course.
      The pre- and post-test survey analysis indicated that students improved their
      attitude, knowledge and preparedness to care for persons with mental illness.
      However, students maintained little interest in working as a mental health nurse.
      Modifications in mental health nursing courses could be made to improve students'
      interest in choosing a career in mental health nursing.

PMID- 28448232
TI  - Dynamic Contrast-enhanced MR Imaging Parameters in Bone Metastases from Non-Small
      Cell Lung Cancer: Comparison between Lesions with and Lesions without Epidermal
      Growth Factor Receptor Mutation in Primary Lung Cancer.
AB  - Purpose To compare dynamic contrast material-enhanced (DCE) magnetic resonance
      (MR) imaging parameters between metastatic bone lesions with and without the
      epidermal growth factor receptor (EGFR) mutation in consecutive patients with
      primary non-small cell lung cancer (NSCLC). Materials and Methods This study was
      approved by the institutional review board. Forty-seven patients with NSCLC and a
      confirmed EGFR mutation status (27 patients were positive and 26 were negative
      for EGFR mutation), who underwent DCE MR imaging for bone metastases between
      November 2012 and March 2016, were included in this study. Two radiologists
      independently analyzed the volume transfer constant (Ktrans), reflux rate (kep),
      and volume fraction of the extravascular extracellular matrix (ve) using image
      processing software. Intergroup comparisons of the mean measured parameters were
      performed with the Mann-Whitney U test. Interobserver agreement was calculated
      with the intraclass correlation coefficient. Results There was a high level of
      agreement between the two reviewers for all three parameters (intraclass
      correlation coefficient = 0.95 for Ktrans, 0.97 for kep, and 0.91 for ve). Ktrans
      was significantly higher in the EGFR mutation-positive group (P = .039 for
      reviewer 1, P = .032 for reviewer 2). kep was also higher in the EGFR mutation
      positive group but showed statistical significance only in the evaluation
      performed by one reviewer (P = .048 for reviewer 2, P = .058 for reviewer 1). No
      significant difference was observed in ve (P = .873 for reviewer 1, P = .889 for
      reviewer 2). Conclusion The differences in the DCE MR imaging parameters between
      metastatic bone lesions with and without EGFR mutations in primary NSCLC may be
      attributed to differences in the vascular structure related to angiogenesis
      stimulated by the activation of the EGFR signaling pathway. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 28448233
TI  - T1 and T2 Mapping in Recognition of Early Cardiac Involvement in Systemic
      Sarcoidosis.
AB  - Purpose To determine whether quantitative tissue characterization with T1 and T2
      mapping supports recognition of myocardial involvement in patients with systemic
      sarcoidosis. Materials and Methods Fifty-three consecutive patients with a biopsy
      proven extracardiac diagnosis of systemic sarcoidosis (21 men; median age, 45
      years; interquartile range, 22 years) and 36 normotensive previously healthy
      control subjects (14 men; median age, 43 years; interquartile range, 18 years)
      underwent cardiovascular magnetic resonance imaging, which was performed to
      assess cardiac function and late gadolinium enhancement, and T1 and T2 mapping. A
      follow-up substudy was performed in 40 patients (mean follow-up interval, 144
      days +/- 35 [standard deviation]); of these 40 patients, 18 underwent anti
      inflammatory treatment for systemic symptoms. Binary logistic regression and
      receiver operating characteristic curve analyses were used to assess
      discrimination between health and disease; Wilcoxon signed rank test was used to
      assess the effect of treatment. Results When compared with control subjects,
      patients had higher ventricular volume, higher myocardial native T1 and T2, and
      lower longitudinal strain and ejection fraction (P < .05 for all). Myocardial
      native T1 and T2 had higher discriminatory accuracy (area under the receiver
      operating characteristic curve [AUC]: 0.96 and 0.89, respectively) for separation
      between control subjects and patients when compared with the standard diagnostic
      criteria (AUC < 0.67). Native T1 was the independent discriminator between health
      and disease (specificity, 90%; sensitivity, 96%; accuracy, 94%). There was a
      significant reduction of native T1 and T2 in the patients who underwent treatment
      (z score: -3.72 and -2.88; P < .01) but not in the patients who did not (z score,
      -1.42 and -1.38; P > .15). Conclusion Quantitative myocardial tissue
      characterization with T1 and T2 mapping may enable noninvasive recognition of
      cardiac involvement and activity of myocardial inflammation in patients with
      systemic sarcoidosis. Future studies will be performed to confirm their role in
      risk stratification and guidance of clinical management. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 28448234
TI  - Leveraging Clinical Imaging Archives for Radiomics: Reliability of Automated
      Methods for Brain Volume Measurement.
AB  - Purpose To validate the use of thick-section clinically acquired magnetic
      resonance (MR) imaging data for estimating total brain volume (TBV), gray matter
      (GM) volume (GMV), and white matter (WM) volume (WMV) by using three widely used
      automated toolboxes: SPM ( www.fil.ion.ucl.ac.uk/spm/ ), FreeSurfer (
      surfer.nmr.mgh.harvard.edu ), and FSL (FMRIB software library; Oxford Centre for
      Functional MR Imaging of the Brain, Oxford, England,
      https://fsl.fmrib.ox.ac.uk/fsl ). Materials and Methods MR images from a clinical
      archive were used and data were deidentified. The three methods were applied to
      estimate brain volumes from thin-section research-quality brain MR images and
      routine thick-section clinical MR images acquired from the same 38 patients (age
      range, 1-71 years; mean age, 22 years; 11 women). By using these automated
      methods, TBV, GMV, and WMV were estimated. Thin- versus thick-section volume
      comparisons were made for each method by using intraclass correlation
      coefficients (ICCs). Results SPM exhibited excellent ICCs (0.97, 0.85, and 0.83
      for TBV, GMV, and WMV, respectively). FSL exhibited ICCs of 0.69, 0.51, and 0.60
      for TBV, GMV, and WMV, respectively, but they were lower than with SPM.
      FreeSurfer exhibited excellent ICC of 0.63 only for TBV. Application of SPM's
      voxel-based morphometry on the modulated images of thin-section images and
      interpolated thick-section images showed fair to excellent ICCs (0.37-0.98) for
      the majority of brain regions (88.47% [306924 of 346916 voxels] of WM and 80.35%
      [377 282 of 469 502 voxels] of GM). Conclusion Thick-section clinical-quality MR
      images can be reliably used for computing quantitative brain metrics such as TBV,
      GMV, and WMV by using SPM. (c) RSNA, 2017 Online supplemental material is
      available for this article.

PMID- 28448235
TI  - Intracranial Artery Steno-Occlusion: Diagnosis by Using Two-dimensional Spatially
      Selective Radiofrequency Excitation Pulse MR Imaging.
AB  - Purpose To determine whether magnetic resonance (MR) imaging by using two
      dimensional spatially selective radiofrequency (RF) excitation pulses (zoomed MR
      imaging) is a reliable method for the diagnosis of intracranial artery steno
      occlusion compared with full-field-of-view (FOV) MR imaging. Materials and
      Methods The institutional review board approved this retrospective study and
      informed consent was waived. From December 2014 to August 2015, 88 patients who
      underwent both full-FOV MR imaging and zoomed MR imaging for further evaluation
      of intracranial artery steno-occlusion at prior luminal evaluation were included.
      Two neuroradiologists independently diagnosed the diseases (atherosclerosis,
      dissection, moyamoya disease, vasculitis, undetermined diagnosis, and no vascular
      pathologic condition) based on both clinical information and MR imaging features
      and assessed diagnosis-related parameters (diameter, length, eccentricity index,
      eccentricity, signal intensity ratio, vessel wall hemorrhage, and the total
      number of lesions), as well as image quality parameters (signal-to-noise ratio
      and image quality scale) with full-FOV MR imaging and zoomed MR imaging.
      Parametric measurements were compared between full-FOV MR imaging and zoomed MR
      imaging by using paired t test and McNemar test. The criterion for intermethod
      reliability was that the upper limit of the 95% confidence interval (CI) in the
      difference of agreement was less than 10% based on a noninferiority test. Results
      The pooled agreement for diagnosing the disease between full-FOV MR imaging and
      zoomed MR imaging was 93% (164 of 176 lesions). The difference of agreement was
      2.84% (one-sided 95% CI: -0.49%, 6.17%). The diagnosis-related parameters were
      not significantly different between both methods (all P > .05), with good to
      excellent agreement (both intraclass correlation coefficient and kappa value
      >=0.61). However, full-FOV MR imaging had better image quality parameters than
      zoomed MR imaging, including precontrast signal-to-noise ratio and image quality
      scale (both P < .05). Conclusion Zoomed MR imaging is a reliable method for the
      diagnosis of intracranial artery steno-occlusion compared with full-FOV MR
      imaging. (c) RSNA, 2017 Online supplemental material is available for this
      article. An earlier incorrect version of this article appeared online. This
      article was corrected on May 2, 2017.

PMID- 28448236
TI  - Development of a French Version of the Edmonton Symptom Assessment System
      Revised: A Pilot Study of Palliative Care Patients' Perspectives.
AB  - BACKGROUND: The Edmonton Symptom Assessment System-revised (ESAS-r) is a nine
      item self-report symptom intensity tool developed for palliative care patients,
      with the option of adding a 10th patient-specific symptom. Due to growing
      international uptake, the ESAS-r has been translated into different languages.
      There has not been agreement, however, regarding a standard process for
      translation into multiple languages, which also includes patients' perspectives.
      OBJECTIVE: The purpose of this study was to develop a French version of the ESAS
      r, using a standardized translation protocol, and to obtain palliative care
      patients' perspectives regarding this translated tool. DESIGN: We developed a
      French version of the ESAS-r, using a standard translation method, involving both
      professional translators (n = 2) and bilingual palliative care experts (n = 3).
      Fifteen Francophone participants recruited from palliative care sites in two
      urban centers in Canada completed the ESAS-r and provided feedback on the
      translation, in the presence of a trained interviewer. Descriptive statistics and
      thematic analysis were used to analyze the quantitative and qualitative data,
      respectively. SETTING/SUBJECTS: Fifteen Francophone participants were recruited
      from palliative care sites in two urban centers in Canada. MEASUREMENTS:
      Participants completed the ESAS-r and provided feedback on the translation in the
      presence of a trained interviewer. Descriptive statistics and thematic analysis
      were used to analyze the quantitative and qualitative data, respectively.
      RESULTS: Based on participants' concerns, translations for four of the nine
      symptoms were revised: drowsiness, nausea, lack of appetite, and shortness of
      breath. Concerns expressed for three additional symptoms (depression, anxiety,
      and well-being) were related to overall difficulty rating these symptoms, not
      specific to the translation. CONCLUSION: The French version of the ESAS-r is a
      credible tool for symptom assessment in Francophone patients. The study findings
      provide a vital step in the development of a standardized translation protocol,
      including patients' perspectives, which can be applied to other languages.

PMID- 28448237
TI  - Regulatory T Cell Therapy for Uveitis: A New Promising Challenge.
AB  - Uveitis is a sight-threatening primary intraocular inflammation of various
      origins in mainly young and active patients. Due to the absence of biomarkers in
      most of the cases, the current treatment of noninfectious entities remains
      nonspecific, using corticosteroids, conventional immunosuppressors, and more
      recently biological agents. Identification of regulatory T cells in different
      models of autoimmune uveitis together with the evaluation of this important
      subpopulation in different entities paved the way for new therapeutic strategies,
      in addition to exclusive pharmaceutical approaches. Upregulation of regulatory T
      cells induced by biological agents has been recently highlighted. Development of
      cell therapy in autoimmune diseases is at its stammering needing more
      experimental data and robust clinical trials to demonstrate safety and efficacy
      before larger developments. Specific or polyclonal Tregs may be used, but it is
      of utmost importance to determine the method of selection, the level of
      activation, and the route of administration. Mastering immune cell therapy
      remains a challenging goal in patients with autoimmune diseases, but it may
      significantly enlarge our therapeutic possibilities in severe and refractory
      situations.

PMID- 28448238
TI  - Single Dexamethasone Intravitreal Implant in the Treatment of Noninfectious
      Uveitis.
AB  - PURPOSE: To investigate the effect of a single intravitreal dexamethasone implant
      (IVT-DI; Ozurdex; Allergan, Inc.) on visual acuity, macular thickness, and
      intraocular pressure (IOP) in active noninfectious uveitis. METHODS: Medical
      records of patients with noninfectious active uveitis treated by IVT-DIs were
      retrospectively reviewed. Uveitis etiologies, treatment indications, best
      corrected visual acuity (BCVA), central retinal thickness measured by ocular
      coherence tomography, IOP, and systemic, local, and topical treatments were
      collected. Parameters were analyzed before the injection of the implant, after
      1.5 +/- 0.8 months and 4.4 +/- 0.9 months for the BCVA, after 2 +/- 1.3 months
      and 4.6 +/- 1.3 months for the ocular coherence tomography, and after 1.3 +/- 0.7
      months and 4.4 +/- 1 months for the IOP. RESULTS: We included 14 patients (20
      eyes, 20 implant injections) with cystoid macular edema (78%), vasculitis (7%),
      choroiditis (7%), and vasculitis associated with choroiditis (7%). Before the
      injection, mean visual acuity was 0.4 +/- 0.5 logMAR (logarithm of the minimum
      angle of resolution) that improved to 0.3 +/- 0.5 logMAR (P = 0.0002) after 1.5
      +/- 0.8 months and to 0.3 +/- 0.5 logMAR (P = 0.005) after 4.4 +/- 0.9 months. A
      statistically significant decrease of macular thickness was observed both at 2 +/
      1.3 months and at 4.6 +/- 1.3 months after IVT-DI. Mean IOP was 16 +/- 5 mmHg
      before injections, 18 +/- 6 mmHg (P = 0.13) at 1.3 +/- 0.7 months, and 15 +/- 4
      mmHg (P = 0.65) at 4.4 +/- 1 months. By Kaplan-Meier analysis, we found that
      after 3.3 months, 17% of the eyes still present a BCVA amelioration >=0.3 logMAR.
      CONCLUSIONS: In our patients with active noninfectious uveitis, injection of a
      first single dexamethasone implant was found to improve visual acuity and
      decrease macular thickness without significant increase of IOP, although the
      effect seems limited in time.

PMID- 28448239
TI  - Extranodal Marginal Zone Lymphoma: No Longer Just a Sidekick.
AB  - The Oncology Grand Rounds series is designed to place original reports published
      in the Journal into clinical context. A case presentation is followed by a
      description of diagnostic and management challenges, a review of the relevant
      literature, and a summary of the authors' suggested management approaches. The
      goal of this series is to help readers better understand how to apply the results
      of key studies, including those published in Journal of Clinical Oncology, to
      patients seen in their own clinical practice. A 51-year-old healthy female with
      good performance status presented for gynecologic surgery for a benign condition.
      A preprocedure chest x-ray showed a right lower lobe infiltrate. A subsequent
      computed tomography (CT) scan of the chest with contrast revealed a large
      consolidative right lower lobe mass with surrounding inflammation ( Fig 1A ).
      Bronchoscopy with biopsy revealed a low-grade lymphoma with the following
      immunophenotype: CD45+, CD20+, BCL2+, CD10 negative, CD5 negative, cyclin D1
      negative, and Ki-67 index of less than 5%. Morphology and immunohistochemistry
      were most consistent with pulmonary extranodal marginal zone lymphoma (ENMZL; Fig
      2 ). The patient was asymptomatic and denied fevers, sweats, weight loss,
      shortness of breath or dyspnea on exertion, or cough. Her history was notable for
      exposure to parrots over several months before presentation. Complete staging
      with a CT of the chest, abdomen, and pelvis with contrast redemonstrated disease
      that was localized to the chest with mild compression of the pulmonary
      vasculature but no other evidence of lymphoma. She was referred to discuss
      management of stage IAE pulmonary ENMZL lymphoma.

PMID- 28448240
TI  - Searching for Happiness.

PMID- 28448242
TI  - The Tom Rowland Series: A Forum Exploring New Challenges facing Pediatric
      Exercise Science.

PMID- 28448243
TI  - The patient experience of illness, treatment, and change, during intensive
      community treatment for severe anorexia nervosa.
AB  - This study explores experiences of intensive community treatment, illness, and
      change among patients with severe anorexia nervosa (sAN), particularly seeking to
      understand the processes involved in change and inability to change. A
      qualitative design with purposive semi-stratified sampling, using semi-structured
      interviews and interpretive phenomenological analysis, investigated in detail the
      experiences of five participants. Participants all had sAN at the start of
      treatment and represented a spectrum of outcomes from deterioration to full
      recovery. Six super-ordinate themes emerged from the analysis: treatment
      experience, function of anorexia, self-criticism versus self-acceptance,
      isolation versus connection, hopelessness versus hope, and stuckness versus
      change. Results describe the valued function of the illness, barriers to change,
      the lengthy struggle for change, and how this can be supported by intensive
      community-based treatment. Necessary ingredients in the process of change,
      arising from the analysis, are proposed. We conclude that the experiences of
      these patients reflect the particular functions of AN for each individual, and
      that both clinical deterioration and full recovery can occur with prolonged
      intensive community treatment.

PMID- 28448244
TI  - Perceptions of disordered eating and associated help seeking in young women.
AB  - Disordered eating is common among young women, but rates of help-seeking are
      remarkably low. Studies attempting to understand how disordered eating is
      perceived by young women have exposed participants to fictional vignettes that
      describe characters exhibiting eating pathologies, and assessed beliefs about the
      women's issues. These studies have informed our understanding of how young women
      perceive disordered eating in other women, but do not address the question of how
      disordered eating is perceived in oneself. In the present study, we randomly
      assigned 204 young women (ages 18-25 years) to one of two conditions (self or
      other). In each condition, participants read a hypothetical vignette in which the
      main character (the participant herself [self] or another female student [other])
      exhibited disordered eating, and answered questions about her behavior and her
      need for help. Data were analyzed using Pearson correlations, chi square tests,
      multiple regression analyses, multinomial logistic regressions, and independent
      samples t-tests. Overall, results supported the existence of a broad discrepancy
      in how young women perceive disordered eating in themselves versus in other
      women. Specifically, relative to women who read the vignette about another
      individual, women who read the vignette about themselves were more likely to
      attribute their behavior to a general mental health issue (as opposed to an
      eating disorder); to believe that they were able to cope with their problem
      alone; and to believe that they did not need to seek help for their eating
      behaviors (despite perceiving fewer barriers to doing so). These findings
      highlight the need for empirical research to consider this self-other discrepancy
      when using findings to inform the development of disordered eating prevention and
      intervention programs; if not considered, we risk developing programs based on
      information that may not accurately represent the young women in need of
      services.

PMID- 28448245
TI  - Temperament-Character Profile and Psychopathologies in Patients with Alopecia
      Areata.
AB  - The aim of this study is to investigate psychopathologies and the temperament
      character profile of Alopecia Areata patients and to compare them with healthy
      controls. Patients and controls who presented at a dermatology clinic were
      selected by convenience sampling to respond to Temperament and Character
      Inventory (TCI), SCL-90-R, and a checklist about the demographic data and their
      dermatologic and psychiatric history. Patients reported higher harm avoidance and
      reward dependence than controls (Cohen's d = .93 and = .94). A significant
      correlation between Harm Avoidance (r = -0.33, p = .02) and Reward Dependence (r
      = -0.28, p = 0.05) with sex was found (females scored higher). Lifetime history
      of AA relapse was significantly associated with higher psychiatric symptoms; the
      effect sizes were large for Obsessive-Compulsive (d = .81) and Paranoia Ideation
      (d = .89). The higher psychological symptoms in AA patients with the history of
      relapses in this study have a practical message for clinicians.

PMID- 28448246
TI  - Pornography Use and Loneliness: A Bidirectional Recursive Model and Pilot
      Investigation.
AB  - Sexuality is presumptively and observably a powerful core element of the human
      pair-bond relationship. Technological advances of the last half-century have made
      media a dominant cultural and developmental presence, including scripting sexual
      relationship attitudes and behavior. Theoretically and empirically, we examine
      loneliness as it relates to pornography use in terms of pornography's relational
      scripting and its addictive potential. Empirically, we examine the associative
      nature between pornography use and loneliness using a measurement model and two
      structural equation models where pornography use and loneliness are regressed on
      each other, respectively. Survey data were collected from a sample of 1,247
      participants, who completed an online questionnaire containing questions on
      pornography use, the University of California-Los Angeles Loneliness Scale
      (UCLALS), and other demographic variables. Results from our analyses revealed
      significant and positive associations between pornography use and loneliness for
      all three models. Findings provide grounds for possible future bidirectional,
      recursive modeling of the relation between pornography use and loneliness.

PMID- 28448247
TI  - Oleuropein isolated from Fraxinus rhynchophylla inhibits glutamate-induced
      neuronal cell death by attenuating mitochondrial dysfunction.
AB  - Glutamate-induced neurotoxicity is related to excessive oxidative stress
      accumulation and results in the increase of neuronal cell death. In addition,
      glutamate has been reported to lead to neurodegenerative diseases, including
      Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla
      contains a significant level of oleuropein (Ole), which exerts various
      pharmacological effects. However, the mechanism of neuroprotective effects of Ole
      is still poorly defined. In this study, we aimed to investigate whether Ole
      prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells. The
      exposure of the glutamate treatment caused neuronal cell death through an
      alteration of Bax/Bcl-2 expression and translocation of mitochondrial apoptosis
      inducing factor (AIF) to the cytoplasm of HT-22 cells. In addition, glutamate
      induced an increase in dephosphorylation of dynamin-related protein 1 (Drp1),
      mitochondrial fragmentation, and mitochondrial dysfunction. The pretreatment of
      Ole decreased Bax expression, increased Bcl-2 expression, and inhibited the
      translocation of mitochondrial AIF to the cytoplasm. Furthermore, Ole amended a
      glutamate-induced mitochondrial dynamic imbalance and reduced the number of cells
      with fragmented mitochondria, regulating the phosphorylation of Drp1 at amino
      acid residue serine 637. In conclusion, our results show that Ole has a
      preventive effect against glutamate-induced toxicity in HT-22 hippocampal
      neuronal cells. Therefore, these data imply that Ole may be an efficient approach
      for the treatment of neurodegenerative diseases.

PMID- 28448248
TI  - The relationship between stressors and mental health among Japanese middle-aged
      women in urban areas.
AB  - In middle age, some people may become mentally or emotionally unstable.
      Additionally, in Japan, mood disorders, such as depressive symptoms, occur mostly
      among middle-aged women (i.e., aged 40-49 years). However, few studies have
      examined stressors related to mental health. In the present study, we developed a
      stressor scale for middle-aged women and examined stressors correlated with
      middle-aged women's mental health. In January 2015, an anonymous, self
      administered survey was mailed to 1,000 randomly selected women aged 45 through
      64 years living in Tokyo, Japan. Completed questionnaires were obtained from 329
      women (32.9 percent). Factor analysis identified the following stressor
      categories: "relationship with my husband," "uneasiness about old age," "health
      concerns," "work-life balance," and "relationship with my friends." "Uneasiness
      about old age" and "health concerns" were correlated negatively with
      participants' mental health. Improving middle-aged women's health requires
      interventions that relieve stressors resulting from age-related problems and
      promote a positive image of old age.

PMID- 28448249
TI  - Relationships among exercise beliefs, physical exercise, and subjective well
      being: Evidence from Korean middle-aged adults.
AB  - Physically active leisure plays a key role in successful aging. Exercise beliefs
      are one of the key predictors of exercise behavior. We used structural equation
      modeling to assess the plausibility of a conceptual model specifying hypothesized
      linkages among middle-aged adults' perceptions of (a) exercise beliefs, (b)
      physical exercise behavior, and (c) subjective well-being. Four hundred two
      adults in South Korea responded to survey questions designed to capture the above
      constructs. We found that physically active leisure participation leads to
      subjective well-being for both middle-aged men and women. However, men and women
      exercised for different reasons. Women exercised for the sake of their physical
      appearance and mental and emotional functioning, whereas men exercised for the
      sake of their social desirability and vulnerability to disease and aging. Based
      on our results, we suggest that men tend to show higher social face sensitivity,
      while women show more appearance management behavior. Based on these findings, we
      discussed the implications and future research directions.

PMID- 28448251
TI  - Erratum, Vol. 13, March 17 Release.
AB  - [This corrects the article DOI: 10.5888/pcd13.150395.].

PMID- 28448250
TI  - Recruiting Community Partners for Veggie Van: Strategies and Lessons Learned From
      a Mobile Market Intervention in North Carolina, 2012-2015.
AB  - BACKGROUND: Food access interventions are promising strategies for improving
      dietary intake, which is associated with better health. However, studies
      examining the relationship between food access and intake are limited to
      observational designs, indicating a need for more rigorous approaches. The Veggie
      Van (VV) program was a cluster-randomized intervention designed to address the
      gap between food access and intake. In this article, we aim to describe the
      approaches involved in recruiting community partners to participate in VV.
      COMMUNITY CONTEXT: The VV mobile market aimed to improve access to fresh fruits
      and vegetables by providing subsidized, high-quality, local produce in low
      resource communities in North Carolina. This study describes the strategies and
      considerations involved in recruiting community partners and individual
      participants for participation in the VV program and evaluation. METHODS: To
      recruit partners, we used various strategies, including a site screener to
      identify potential partners, interest forms to gauge future VV use and prioritize
      enrollment of a high-need population, marketing materials to promote VV, site
      liaisons to coordinate community outreach, and a memorandum of understanding
      between all invested parties. OUTCOME: A total of 53 community organizations and
      725 participants were approached for recruitment. Ultimately, 12 sites and 201
      participants were enrolled. Enrollment took 38 months, but our approaches helped
      successfully recruit a low-income, low-access population. The process took longer
      than anticipated, and funding constraints prevented certain strategies from being
      implemented. INTERPRETATION: Recruiting community partners and members for
      participation in a multi-level, community-based intervention was challenging.
      Strategies and lessons learned can inform future studies.

PMID- 28448252
TI  - Hypothyroidism in Carcinoma of the Tongue with Adjuvant Treatment.
AB  - OBJECTIVE: The objective of this study was to evaluate the incidence of
      hypothyroidism with adjuvant treatment in oral tongue carcinoma patients treated
      primarily with surgery. MATERIALS AND METHODS: A retrospective review was carried
      out to analyze hypothyroidism incidence and its relation to adjuvant treatment
      (radiation/radio-chemotherapy) in oral tongue carcinoma after the primary
      surgical ablation and neck dissection. Hypothyroidism was analyzed in relation
      with dose of radiation, gender, and adjuvant treatment modality. RESULTS: The
      study analyzed the patients who were treated between January 2012 and June 2015.
      Among 705 patients with carcinoma of the tongue treated primarily with wide local
      excision and neck dissection, 383 received adjuvant treatment. A total of 215
      patients received radiation, and 168 received concurrent radio-chemotherapy. Of
      378 patients, 78 developed hypothyroidism during follow-up: 27 patients received
      concurrent radio-chemotherapy, and the remaining 51 received only radiation.
      Lower neck received 40-48 Gy in 2 patients, 50 Gy in 74 patients, and 60-70 Gy
      and concurrent radio-chemotherapy in 27 patients. Median follow-up was 32 months.
      Hypothyroidism occurred in 21.5% of patients with squamous cell carcinoma of the
      oral tongue. The minimum period to develop hypothyroidism was 3 months in this
      study. Gender and adjuvant treatment were not found to be significant for the
      incidence of hypothyroidism. CONCLUSIONS: A significant number of patients with
      carcinoma of the tongue who receive adjuvant treatment will develop
      hypothyroidism, hence frequent monitoring of thyroid function is advised during
      follow-up.

PMID- 28448254
TI  - TAFRO syndrome or Castleman-Kojima syndrome: a variant of multicentric Castleman
      disease.

PMID- 28448253
TI  - A map of abstract relational knowledge in the human hippocampal-entorhinal
      cortex.
AB  - The hippocampal-entorhinal system encodes a map of space that guides spatial
      navigation. Goal-directed behaviour outside of spatial navigation similarly
      requires a representation of abstract forms of relational knowledge. This
      information relies on the same neural system, but it is not known whether the
      organisational principles governing continuous maps may extend to the implicit
      encoding of discrete, non-spatial graphs. Here, we show that the human
      hippocampal-entorhinal system can represent relationships between objects using a
      metric that depends on associative strength. We reconstruct a map-like knowledge
      structure directly from a hippocampal-entorhinal functional magnetic resonance
      imaging adaptation signal in a situation where relationships are non-spatial
      rather than spatial, discrete rather than continuous, and unavailable to
      conscious awareness. Notably, the measure that best predicted a behavioural
      signature of implicit knowledge and blood oxygen level-dependent adaptation was a
      weighted sum of future states, akin to the successor representation that has been
      proposed to account for place and grid-cell firing patterns.

PMID- 28448255
TI  - Children, Adolescents, and the Media.
AB  - Media, from television to the "new media" (including cell phones, iPads, and
      social media), are a dominant force in children's lives. Although television is
      still the predominant medium for children and adolescents, new technologies are
      increasingly popular. The American Academy of Pediatrics continues to be
      concerned by evidence about the potential harmful effects of media messages and
      images; however, important positive and prosocial effects of media use should
      also be recognized. Pediatricians are encouraged to take a media history and ask
      2 media questions at every well-child visit: How much recreational screen time
      does your child or teenager consume daily? Is there a television set or Internet
      connected device in the child's bedroom? Parents are encouraged to establish a
      family home use plan for all media. Media influences on children and teenagers
      should be recognized by schools, policymakers, product advertisers, and
      entertainment producers.

PMID- 28448256
TI  - Pediatric Palliative Care and Hospice Care Commitments, Guidelines, and
      Recommendations.
AB  - Pediatric palliative care and pediatric hospice care (PPC-PHC) are often
      essential aspects of medical care for patients who have life-threatening
      conditions or need end-of-life care. PPC-PHC aims to relieve suffering, improve
      quality of life, facilitate informed decision-making, and assist in care
      coordination between clinicians and across sites of care. Core commitments of PPC
      PHC include being patient centered and family engaged; respecting and partnering
      with patients and families; pursuing care that is high quality, readily
      accessible, and equitable; providing care across the age spectrum and life span,
      integrated into the continuum of care; ensuring that all clinicians can provide
      basic palliative care and consult PPC-PHC specialists in a timely manner; and
      improving care through research and quality improvement efforts. PPC-PHC
      guidelines and recommendations include ensuring that all large health care
      organizations serving children with life-threatening conditions have dedicated
      interdisciplinary PPC-PHC teams, which should develop collaborative relationships
      between hospital- and community-based teams; that PPC-PHC be provided as
      integrated multimodal care and practiced as a cornerstone of patient safety and
      quality for patients with life-threatening conditions; that PPC-PHC teams should
      facilitate clear, compassionate, and forthright discussions about medical issues
      and the goals of care and support families, siblings, and health care staff; that
      PPC-PHC be part of all pediatric education and training curricula, be an active
      area of research and quality improvement, and exemplify the highest ethical
      standards; and that PPC-PHC services be supported by financial and regulatory
      arrangements to ensure access to high-quality PPC-PHC by all patients with life
      threatening and life-shortening diseases.

PMID- 28448257
TI  - Condom Use by Adolescents.
AB  - Rates of sexual activity, pregnancies, and births among adolescents have
      continued to decline during the past decade to historic lows. Despite these
      positive trends, many adolescents remain at risk for unintended pregnancy and
      sexually transmitted infections (STIs). This policy statement has been developed
      to assist the pediatrician in understanding and supporting the use of condoms by
      their patients to prevent unintended pregnancies and STIs and address barriers to
      their use. When used consistently and correctly, male latex condoms reduce the
      risk of pregnancy and many STIs, including HIV. Since the last policy statement
      published 12 years ago, there is an increased evidence base supporting the
      protection provided by condoms against STIs. Rates of acquisition of STIs/HIV
      among adolescents remain unacceptably high. Interventions that increase
      availability or accessibility to condoms are most efficacious when combined with
      additional individual, small-group, or community-level activities that include
      messages about safer sex. Continued research is needed to inform public health
      interventions for adolescents that increase the consistent and correct use of
      condoms and promote dual protection of condoms for STI prevention with other
      effective methods of contraception.

PMID- 28448259
TI  - Prevention and Control of Meningococcal Disease: Recommendations of the Advisory
      Committee on Immunization Practices (ACIP).

PMID- 28448258
TI  - Guiding Principles for Managed Care Arrangements for the Health Care of Newborns,
      Infants, Children, Adolescents, and Young Adults.
AB  - By including the precepts of primary care and the medical home in the delivery of
      services, managed care can be effective in increasing access to a full range of
      health care services and clinicians. A carefully designed and administered
      managed care plan can minimize patient under- and overutilization of services, as
      well as enhance quality of care. Therefore, the American Academy of Pediatrics
      urges the use of the key principles outlined in this statement in designing and
      implementing managed care programs for newborns, infants, children, adolescents,
      and young adults to maximize the positive potential of managed care for
      pediatrics. These principles include the following.

PMID- 28448260
TI  - The Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV
      Infected Children.

PMID- 28448261
TI  - Best Practices for Sports Medicine Management for Secondary Schools and Colleges.

PMID- 28448241
TI  - Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation
      Carriers Using Polygenic Risk Scores.
AB  - Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men.
      Common genetic variants modify cancer risks for female carriers of BRCA1/2
      mutations. We investigated-for the first time to our knowledge-associations of
      common genetic variants with breast and prostate cancer risks for male carriers
      of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and
      Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium
      of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray.
      We investigated the combined effects of established breast and prostate cancer
      susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by
      constructing weighted polygenic risk scores (PRSs) using published effect
      estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was
      based on 88 female breast cancer susceptibility variants was associated with
      breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19
      to 1.56; P = 8.6 * 10-6). Similarly, PRS that was based on 103 prostate cancer
      susceptibility variants was associated with prostate cancer risk (odds ratio per
      SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 * 10-9). Large differences in
      absolute cancer risks were observed at the extremes of the PRS distribution. For
      example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of
      the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61%
      for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide
      informative cancer risk stratification for male carriers of BRCA1/2 mutations
      that might enable these men and their physicians to make informed decisions on
      the type and timing of breast and prostate cancer risk management.

PMID- 28448262
TI  - An Unusually Large Carbuncle of the Temporofacial Region Demonstrating Remarkable
      Post-debridement Wound Healing Process: A Case Report.
AB  - Skin carbuncles are debilitating skin infections commonly seen in elderly
      patients with diabetes. These infections develop when a cluster of adjacent
      furuncles coalesce to form one inflammatory mass. While they commonly occur on
      the nape of the neck and back, rarer sites involving the face and head have been
      noted. Management of these rare sites is urgent because of the potential
      intracranial complications and the surgical outcome is often unsatisfactory due
      to associated facial scarring. Intraoral drainage is advocated to avoid this;
      however, when the carbuncle involves a larger area, debridement from the exterior
      is necessary. The resultant soft-tissue defect requires a skin graft or a flap
      for coverage, but this may still lead to an unsatisfactory cosmetic outcome. The
      authors report a case of a carbuncle involving an extensive area over the right
      temporofacial region, including its management and the remarkable post
      debridement cosmetic outcome despite avoidance of plastic surgery techniques due
      to the patient's high risk associated with anesthesia.

PMID- 28448263
TI  - Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.
AB  - Our understanding of the role of zinc in normal human physiology is constantly
      expanding, yet there are major gaps in our knowledge with regard to the function
      of zinc in wound healing. This review aims to provide the clinician with
      sufficient understanding of zinc biology and an up-to-date perspective on the
      role of zinc in wound healing. Zinc is an essential ion that is crucial for
      maintenance of normal physiology, and zinc deficiency has many manifestations
      ranging from delayed wound healing to immune dysfunction and impairment of
      multiple sensory systems. While consensus has been reached regarding the
      detrimental effects of zinc deficiency on wound healing, there is considerable
      discord in the literature on the optimal methods and true benefits of zinc
      supplementation.

PMID- 28448264
TI  - Use of Ovine-based Collagen Extracellular Matrix and Gentian Violet/Methylene
      Blue Antibacterial Foam Dressings to Help Improve Clinical Outcomes in Lower
      Extremity Wounds: A Retrospective Cohort Study.
AB  - : Dressings that provide broad spectrum metalloprotease reduction along with
      inherent aspects of an extracellular matrix may contribute to improved wound
      healing outcomes and shorter treatment times. OBJECTIVE: The author performed a
      retrospective case series analysis to determine the clinical outcomes of regular
      debridement with the use of ovine-based collagen extracellular matrix dressings
      and gentian violet/methylene blue polyurethane antibacterial foam dressings in
      treating 53 patients with 53 chronic lower extremity wounds (diabetic foot ulcers
      [DFUs], venous leg ulcers, and heel pressure ulcers). MATERIALS AND METHODS:
      Patients were treated twice weekly in an outpatient clinic for the first 4 weeks
      and weekly thereafter until closure. RESULTS: Average body mass index (BMI) for
      the study population was 28.3, and the average patient age was 75.9 years. Mean
      percent wound surface area reduction at 4, 8, and 12 weeks was 38.5%, 73.3%, and
      91.3%, respectively. Average time to closure for all wounds was 10.6 weeks
      (range, 5-24 weeks). All wounds were 100% reepithelialized by week 20 except 1
      DFU that reepithelialized at week 24. The average cost of care for a single wound
      episode (from presentation to closure) was $2749.49. CONCLUSION: Results of this
      analysis showed that the healing of chronic wounds in this series could be
      achieved at a reasonable cost with regular debridement and a collagen matrix
      dressing regimen, even in patients of advanced age and above average BMI as well
      as in wounds that did not achieve > 40% wound surface area reduction at 4 weeks.

PMID- 28448266
TI  - A Prospective, Randomized, Blinded, Controlled Trial Comparing Transdermal
      Continuous Oxygen Delivery to Moist Wound Therapy for the Treatment of Diabetic
      Foot Ulcers.
AB  - Worldwide, diabetic foot ulcers (DFUs) continue to exact a major burden on
      patients and health care providers. Although hyperbaric oxygen therapy is well
      known as an adjunct option, less is known about the efficacy of transdermal
      continuous oxygen therapy (TCOT). A prospective, randomized, blinded,
      multicenter, parallel study was conducted from October 2009 to November 2012 to
      evaluate healing time and the proportion of DFUs healed after 12 weeks of moist
      wound therapy (MWT) with or without TCOT. Study participants (persons with type 1
      or type 2 diabetes and a nonhealing [>1-month but <1-year duration], 1 cm2 to 10
      cm2 in area, infection-free DFU) were randomized to TCOT or a sham device
      (control) in addition to receiving MWT. TCOT treatment consisted of continuous
      administration of 98+% oxygen to the wound site using a 15-day device with
      dressings changed every 3 to 7 days per care plan or more often when clinically
      required. Potential participants completed demographic and clinical screening and
      wound and laboratory evaluations at baseline, and wound evaluations, evaluation
      of adverse events, debridement, and treatment once weekly until the wound healed
      or up to 12 weeks. The primary endpoint was defined as complete wound closure by
      week 12. Wound measurements were made utilizing acetate tracings. Original
      tracings were collected at approximately 6-week intervals and analyzed upon study
      closure. Data were collected via paper Case Report Forms and entered into an
      electronic database after the patient's final visit. Statistical analysis was
      performed on datasets exported from the electronic database. Wound measurement
      data were analyzed using chi-squared. Time to complete closure was analyzed using
      Kaplan-Meier analysis in conjunction with the log-rank test. Of the 130 potential
      participants, 8 with protocol violations were excluded from analysis. In the
      intent-to-treat (ITT) population (N = 122, average age 59 years [range 28-85
      years]), the majority were male (74%), Caucasian (81%), and had a plantar ulcer
      (76%). Mean baseline wound area was 2.3 +/- 1.7 cm2 (range 0.4-8.9 cm2) and 2.0
      +/- 1.7 cm2 (range 0.6-8.7 cm2) in the control and TCOT groups, respectively.
      HbA1c (%) was 7.9 +/- 1.7 in the control and 8.0 +/- 1.7 in the treatment group.
      In the TCOT group, 35 of 65 (54%) wounds healed compared to 31 of 63 (49%) in the
      control arm (P = .4167). In the per-protocol population (PP) (ie, patients
      without protocol violations), 34 of 61 wounds (56%) in the TCOT group and 31 of
      61 (49%) in the control group healed. In the >=65 years PP subgroup, 14 of 17
      (82%) in the TCOT and 8 of 16 (50%) in the control arm healed (P = .049). Median
      time to complete closure in the PP group was 63 days for the TCOT and 77 days for
      the control group (P >.05). No device-related serious adverse events occurred in
      either group. Wound outcomes of patients in both groups were good, but the TCOT
      device did not appear to offer added benefit over moist wound healing treatment
      and offloading to facilitate the healing of small, nonsevere diabetic foot ulcers
      of relatively healthy patients. The data suggest the device may offer a greater
      benefit to older patients. Studies including a more diverse and larger sample
      patient population are warranted.

PMID- 28448267
TI  - Endogenous Thymosin beta4 Expression in Sacrococcygeal Pilonidal Sinus Disease: A
      Retrospective, Immunohistochemical Analysis of Excisional Skin Biopsy Samples.
AB  - Thymosin beta 4 (Tbeta4) is a peptide that has been shown in dermal, corneal, and
      cardiac preclinical injury models to potentially affect tissue protection,
      regeneration, and repair. Sacrococcygeal pilonidal sinus disease (SPSD) is a
      chronic inflammatory disorder associated with a high incidence of recurrence,
      chronic fistulation, and a challenging postoperative surgical wound healing
      process. Retrospectively, an immunohistochemical analysis was conducted to
      evaluate endogenous Tbeta4 expression in excisional skin biopsies from patients
      with SPSD. Patient demographics (age, gender) and surgical procedure data were
      obtained from their electronic medical records. Two (2) samples were cut from
      each specimen and prepared for histopathological assessment: 1 from the inflamed
      sinus tracts containing hair and granulation tissue (chronic wound group) and 1
      from the normal tissue at least 1 cm away from the sinus tract (control group).
      Tbeta4 expression was evaluated in the epidermal, dermal/subcutaneous collagen,
      and vascular structures of the samples from the sinus tract and healthy tissue.
      Inflamed sinus tract tissue and noninflamed normal tissue adjacent to the sinus
      tract were sampled from each specimen to confirm the diagnosis of SPSD and to
      determine distribution and intensity of Tbeta4 expression. Presence of
      cytoplasmic staining for Tbeta4 was considered in favor of positive Tbeta4
      expression; intensity of Tbeta4 expression was scored as 0 = no staining, 1 =
      mild, 2 = moderate, and 3 = strong level of expression. A total of 31 excisional
      skin biopsy specimens were available from 31 patients with SPSD (mean age 26.0 +/
      7.6 years, 25 [80.6%] men, 6 [19.4%] women) who underwent primary surgical
      closure. Demographic variables were analyzed using descriptive statistics. Data
      compliance with normal distribution was evaluated using the Kolmogorov-Smirnov
      and Shapiro-Wilk tests, and the Mann-Whitney U test was used for comparison of
      numerical data. P <.05 was considered statistically significant. Inflamed sinus
      tract tissue had significantly higher Tbeta4 expression scores than noninflamed
      tissue samples in the epidermis (2.4 +/- 0.8 [1.0-3.0] versus 0.8 +/- 0.5 [0.0
      2.0], P = .000), dermal/subcutaneous collagen (2.6 +/- 0.5 [2.0-3.0] versus 1.6
      +/- 0.5 [1.0-2.0], P = .000), and vascular structure (2.6 +/- 0.5 [2.0-3.0]
      versus 1.1 +/- 0.3 [1.0-2.0], P = .000). Study findings indicate Tbeta4 is
      endogenously expressed in normal skin tissue and is overexpressed in inflamed
      sinus tract tissue in patients with SPSD. Preclinical studies with a larger
      sample size are needed to enhance understanding of the potential role of Tbeta4
      in the inflammatory and tissue remodeling processes of SPSD by elucidating its
      mechanism of action at the molecular level, physiological role, and the
      therapeutic potential in dermal healing.

PMID- 28448268
TI  - The Effect of Pycnogenol on Wound Healing in Diabetic Rats.
AB  - Pycnogenol (PYC), an extract of pine bark, is known to have photoprotective,
      antimicrobial, antioxidant, and anti-inflammatory properties. An in vivo study
      was conducted to evaluate the effects of PYC treatment on wound healing in 48
      adult male Sprague-Dawley rats, of which 24 were injected with a single dose of
      alloxan to induce diabetes. Three (3) excisional skin wounds (1.3 cm x 1.3 cm x 2
      mm) were created in each healthy and diabetic animal. One (1) wound in each
      animal was left untreated, 1 was treated daily with a cleanser (ethacridine
      lactate) and covered with silver sulfadiazine (SSD), and 1 was treated with PYC
      powder (30 mg). After measuring wound size, 6 animals from both groups were
      sacrificed on days 3, 7, 14, and 21 and tissue samples were taken for
      histopathological evaluation of acute and chronic inflammation, granulation
      tissue, fibroblast maturation, collagen deposition, epithelialization, and
      neovascularization using a scoring system of 0 = none, 1 = mild, 2 = moderate,
      and 3 = abundant. Because the wounds created were not uniform in size within and
      among the animals, healing was expressed as a percentage of the initial wound
      size for each animal. Data were compared using 2-way analysis of variance;
      histopathological lesion scores were reported in median values in univariate
      analysis, with P <.05 denoting statistical significance. The mean initial wound
      surface area was 1.69 +/- 0.44 cm2. On day 21, the average reduction in wound
      size was lower in diabetic than in healthy rats (47.42% versus 50.91%, P <.0001)
      and, in both groups combined, the average reduction was 45.73% in untreated,
      48.73% in cleanser/SSD-treated, and 58.03% in PYC-treated wounds (P <.0001).
      Wound size reduction was also significantly different between PYC and the
      cleanser/SSD treatment depending on the rats' health status (P <.0001): 49.68%
      and 47.84% using cleanser/SSD and 56.17% and 49.84% using PYC in healthy and
      diabetic rats, respectively. After 3 weeks, wound size for the healthy rats had
      decreased more than in the diabetic rats (mean 50.91% versus 47.42%). Although
      reepithelialization was complete in both groups by day 21, complete
      neovascularization was evident in the healthy rats but not in the diabetic rats.
      Overall, compared to the untreated control wounds, treatments with cleanser/SSD
      and PYC were equally effective in lowering acute and chronic inflammation scores
      on days 7 and 21. In diabetic rat wounds, collagen deposition and
      neovascularization scores were higher in wounds treated with PYC than
      cleanser/SSD-treated wounds (1.5 versus 1.0 and 2.0 versus 1.5, respectively).
      PYC appears to be a viable option to accelerate wound healing. Further in vivo
      and human research is warranted.

PMID- 28448269
TI  - Circulating cell-free microRNAs as clinical cancer biomarkers.
AB  - MicroRNAs (miRNAs) are non-coding small RNAs that are master regulators of genic
      expression and consequently of many cellular processes. But their expression is
      often deregulated in human tumors leading to cancer development. Recently miRNAs
      were discovered in body fluids (serum, plasma and others) and their levels have
      often been reported to be altered in patients. Circulating miRNAs became one of
      the most promising biomarkers in oncology for early diagnosis, prognosis and
      therapeutic response prediction. Here we describe the origins and roles of
      miRNAs, and summarize the most recent studies focusing on their usefulness as
      cancer biomarkers in lung, breast, colon, prostate, ovary cancers and melanoma.
      Lastly, we describe the main methodologies related to miRNA detection, which
      should be standardized for their use in clinical practice.

PMID- 28448270
TI  - A new in vitro spine test rig to track multiple vertebral motions under
      physiological conditions.
AB  - In vitro pure moment spine tests are commonly used to analyse surgical implants
      in cadaveric models. Most of the tests are performed at room temperature.
      However, some new dynamic instrumentation devices and soft tissues show
      temperature-dependent material properties. Therefore, the aim of this study is to
      develop a new test rig, which allows applying pure moments on lumbar spine
      specimens in a vapour-filled chamber at body temperature. As no direct sight is
      given in the vapour-filled closed chamber, a magnetic tracking (MT) system with
      implantable receivers was used. Four human cadaveric lumbar spines (L2-L5) were
      tested in a vapour atmosphere at body temperature with a native and rigid
      instrumented group. In conclusion, the experimental set-up allows vertebral
      motion tracking of multiple functional spinal units (FSUs) in a moisture
      environment at body temperature.

PMID- 28448271
TI  - Separate patient serum sodium medians from males and females provide independent
      information on analytical bias.
AB  - BACKGROUND: During monitoring of monthly medians of results from patients
      undertaken to assess analytical stability in routine laboratory performance, the
      medians for serum sodium for male and female patients were found to be
      significantly related. METHODS: Daily, weekly and monthly patient medians of
      serum sodium for both male and female patients were calculated from results
      obtained on samples from the population >18 years on three analysers in the
      hospital laboratory. The half-range of medians was applied as an estimate of the
      maximum bias. Further, the ratios between the two medians were calculated.
      RESULTS: The medians of both genders demonstrated dispersions over time, but they
      were closely connected in like patterns, which were confirmed by the half-range
      of the ratios of medians for males and females that varied from 0.36% for daily,
      0.14% for weekly and 0.036% for monthly ratios over all instruments. CONCLUSIONS:
      The tight relationship between the gender medians for serum sodium is only
      possible when raw laboratory data are used for calculation. The two patient
      medians can be used to confirm both and are useful as independent estimates of
      analytical bias during constant calibration periods. In contrast to the gender
      combined median, the estimate of analytical bias can be confirmed further by
      calculation of the ratios of medians for males and females.

PMID- 28448272
TI  - Automated network analysis to measure brain effective connectivity estimated from
      EEG data of patients with alcoholism.
AB  - OBJECTIVE: Detection and diagnosis based on extracting features and
      classification using electroencephalography (EEG) signals are being studied
      vigorously. A network analysis of time series EEG signal data is one of many
      techniques that could help study brain functions. In this study, we analyze EEG
      to diagnose alcoholism. APPROACH: We propose a novel methodology to estimate the
      differences in the status of the brain based on EEG data of normal subjects and
      data from alcoholics by computing many parameters stemming from effective network
      using Granger causality. MAIN RESULTS: Among many parameters, only ten parameters
      were chosen as final candidates. By the combination of ten graph-based
      parameters, our results demonstrate predictable differences between alcoholics
      and normal subjects. A support vector machine classifier with best performance
      had 90% accuracy with sensitivity of 95.3%, and specificity of 82.4% for
      differentiating between the two groups.

PMID- 28448273
TI  - Magnetic induction spectroscopy (MIS)-probe design for cervical tissue
      measurements.
AB  - OBJECTIVE: Gradiometers have the advantage of increasing measuring sensitivity,
      which is particularly useful in magnetic induction spectroscopy (MIS) for bio
      impedance measurements. Traditional gradiometers use a pair of field sensing
      coils equally distant and on opposite sides of a drive coil, which provides high
      immunity to interference. In this paper, a ferrite-cored coaxial gradiometer
      probe of 29 mm diameter has been developed for measuring the impedance spectra of
      cervical tissues in vivo. APPROACH: It consists of a ferrite rod with outer
      ferrite confinement screening in order to eliminate the signals from surrounding
      tissue. The magnetic screening efficiency was compared with an air-cored
      gradiometer probe. For both gradiometer probes, a drive coil and two sensing
      coils were wound on a borosilicate glass former aligned coaxially with two
      sensing coils equidistant from the drive coil. The signal sensitivity of those
      two MIS gradiometers has been measured using saline samples with a conductivity
      range between 0.1 and 1.1 S m-1. Finite element methods using COMSOL Multiphysics
      have been used to simulate the distribution of sensitivity to conductivity over
      the face of each probe and with depth. MAIN RESULTS: The ferrite-cored probe has
      a sensitivity confined to the volume defined by the gap between the ferrite core
      and outer tube of ferrite while the air-cored probe without any magnetic
      shielding had a wide sensitivity over the face and the side of the probe. Four
      saline samples and one of distilled water with conductivities from 0.1 to 1.1 S m
      1 have been used to make conductivity measurements at frequencies of 50 kHz, 100
      kHz, and 300 kHz. The measurement accuracy of the air-cored MIS probe was 0.09 S
      m-1 at 50 kHz, improving to 0.05 S m-1 at 300 kHz. For the ferrite-cored MIS
      probe, the measurement accuracy was 0.28 S m-1 at 50 kHz, improving to 0.04 S m-1
      at 300 kHz. SIGNIFICANCE: In vivo measurements on human hand have been performed
      using both types of gradiometers and the conductivity is consistent with reported
      data.

PMID- 28448274
TI  - Top-down fabricated tapered GaAs nanowires with sacrificial etching of the mask.
AB  - A novel fabrication method using controlled sacrificial etching of the mask is
      utilized to fabricate tapered vertical GaAs nanowire arrays. Experimental
      measurements of the absorption characteristics show that the tapered nanowires
      absorb over a broadband range as compared to cylindrical ones. The broadband
      characterization is verified by using optical modeling and results from improved
      coupling of the nanowires due to distinct radial HE modes being excited
      separately in the taper and the cylindrical part. The absorption is found to be
      more broadband as compared to conical nanowires studied so far.

PMID- 28448275
TI  - Multi-band decomposition analysis: application to cardiac alternans as a function
      of temperature.
AB  - OBJECTIVE: It has long been known that variations in temperature can facilitate
      the development of cardiac arrhythmias. Here, we aim to quantify the effects of
      temperature on cardiac alternans properties. APPROACH: in this work, we use
      optical mapping recordings of canine ventricular epicardial preparations to
      demonstrate that hypothermia can promote the formation of alternans, which is an
      important precursor to potentially lethal arrhythmias like fibrillation. We then
      present a novel quantification of alternans properties for a broad range of cycle
      lengths under different thermal states. Specifically, we apply the recently
      developed multi-band-decomposition analysis (MBDA) in the context of cardiac
      action potential dynamics. MAIN RESULTS: We show that the MBDA offers several
      advantages compared with traditional analysis of action potential durations.
      First, MBDA allows a depiction and quantification of the magnitude of alternans
      at all threshold values simultaneously and thus offers more information about how
      alternans relates to the action potential morphology while also removing the
      necessity of choosing a single threshold value. Second, the MBDA technique offers
      simple ways for assessing action potential amplitude alternans. Finally, MBDA
      provides a quantification of signal quality without any additional processing.
      SIGNIFICANCE: We find that the MBDA technique shows promise in leading to a
      deeper understanding of cardiac alternans properties.

PMID- 28448276
TI  - White light emission of monolithic InGaN/GaN grown on morphology-controlled,
      nanostructured GaN templates.
AB  - We demonstrated an InGaN/GaN-based, monolithic, white light-emitting diode (LED)
      without phosphors by using morphology-controlled active layers formed on multi
      facet GaN templates containing polar and semipolar surfaces. The nanostructured
      surface morphology was controlled by changing the growth time, and distinct
      multiple photoluminescence peaks were observed at 360, 460, and 560 nm; these
      features were caused by InGaN/GaN-based multiple quantum wells (MQWs) on the
      nanostructured facets. The origin of each multi-peak was related to the different
      indium (In) compositions in the different planes of the quantum wells grown on
      the nanostructured GaN. The emitting units of MQWs in the LED structures were
      continuously connected, which is different from other GaN-based nanorod or
      nanowire LEDs. Therefore, the suggested structure had a larger active area. From
      the electroluminescence spectrum of the fabricated LED, monolithic white light
      emission with CIE color coordinates of x = 0.306 and y = 0.333 was achieved via
      multi-facet control combined with morphology control of the metal organic
      chemical vapor deposition-selective area growth of InGaN/GaN MQWs.

PMID- 28448279
TI  - Together into the future... Pharmacogenomics and documentation.

PMID- 28448280
TI  - Letters.

PMID- 28448278
TI  - Reliability and Fall Risk Detection for the BESTest and Mini-BESTest in Older
      Adults.
AB  - BACKGROUND & PURPOSE: Test stability and test-retest reliability have not
      previously been reported for either the Balance Evaluation Systems Test (BESTest)
      or mini-BESTest (mBEST) in a population of older adults with nonspecific balance
      limitations. Furthermore, no criterion for identifying change greater than chance
      has been reported in older adults with nonspecific balance problems using either
      BESTest or mBEST scores. The purposes of this study were to determine test
      stability over time, test-retest reliability, to identify minimum detectable
      change for the BESTest and mBEST in a population of older adults with nonspecific
      balance problems. In addition, the ability of the BESTest and mBEST to identify
      past fallers was characterized. METHODS: This was an observational study with 58
      adults 65 years or older with a history of falls or self-reported balance
      problem. The BESTest and mBEST were administered to all participants at the
      beginning and end of 4 weeks. Test-retest reliability was calculated with
      intraclass correlations, and minimum detectable change was calculated at the 95%
      confidence level (MDC95). Receiver operating characteristics were used to
      characterize the sensitivity and specificity of the BESTest and mBEST to identify
      older adults who had previously fallen. RESULTS: Balance scores did not
      significantly change over a 4-week period. Test-retest reliability for the
      BESTest (0.86) and mBEST (0.84) was good to excellent. MDC95 scores were
      identified for the BESTest (8.9) and mBEST (4). CONCLUSIONS: The BESTest and
      mBEST scores were stable and reliable over a period of 4 weeks for a population
      of older adults with self-reported balance problems or a history of falling.
      MDC95 scores allow interpretation of change in BESTest and mBEST scores following
      rehabilitation.

PMID- 28448282
TI  - Wellness Survey 2017.

PMID- 28448277
TI  - Long-term consequences of obesity on female fertility and the health of the
      offspring.
AB  - PURPOSE OF REVIEW: Obesity has reached near epidemic levels among reproductive
      age women with a myriad of consequences. Obesity adversely affects the maternal
      milieu by creating conditions that decrease fertility and increase the risk of
      gestational diabetes, hypertensive disease in pregnancy, fetal growth
      abnormalities and congenital anomalies. The effects of obesity are not limited to
      pregnancy. Indeed, beyond the immediate postpartum period, obese women maintain a
      higher prevalence of insulin resistance and cardiovascular disease. In this
      article, we will review the pathophysiology underlying the effects of obesity on
      fertility, pregnancy outcome and health status of offspring. The purpose of this
      review is to outline proposed models responsible for the short-term and long-term
      consequences of obesity on fertility and offspring development, and identify
      knowledge gaps where additional research is needed. RECENT FINDINGS: Maternal
      over or under nutrition adversely affect maternal reproductive capacity and
      pregnancy success. Separate from effects on maternal reproductive function,
      maternal over or under nutrition may also 'program' fetal pathophysiology through
      inheritance mechanisms that suggest epigenetic modification of DNA, differential
      RNA translation and protein expression, or modification of the fetal hypothalamic
      pituitary axis function through programmed adverse effects on the developing
      hypothalamic circuitry. The concept of maternal health modifying the risk of
      developing noncommunicable diseases in the offspring is based on Developmental
      Origins of Health and Disease hypothesis. SUMMARY: Of importance, the long-term
      effects of obesity are not limited to maternal health, but also programs
      pathophysiology in their offspring. Children of obese gravida are at increased
      risk for the development of cardiometabolic disease in childhood and throughout
      adulthood. Future studies directly interrogating mechanisms underlying the risks
      associated with obesity will allow us to develop interventions and therapies to
      decrease short-term and long-term morbidities associated with maternal obesity.

PMID- 28448283
TI  - How do you manage the highly skilled, toxic nurse?

PMID- 28448284
TI  - Code Compassion: A caring fatigue reduction intervention.

PMID- 28448285
TI  - Selecting risk scales for clinical practice.

PMID- 28448286
TI  - Profile: Iora Health Transactional vs. relationship-based care.
AB  - Last November, Nursing Management Congress2016 attendees experienced a one-of-a
      kind keynote address when Zubin Damania, MD, took the stage. Through self
      produced song and video, he explored the ethics of delivering compassionate care
      in our challenging healthcare system. Here, read about the Iora Health model that
      Dr. Damania celebrates as "having it right."

PMID- 28448287
TI  - Together into the future...Pharmacogenomics and documentation.
AB  - New partnerships target optimal care quality and outcomes.

PMID- 28448288
TI  - Leadership practices for healthy work environments.

PMID- 28448289
TI  - Team charters: Mapping clearer communication.

PMID- 28448290
TI  - Confronting a coworker's difficult behavior.

PMID- 28448291
TI  - The polypill in cardiovascular prevention: evidence, limitations and perspective 
      position paper of the European Society of Hypertension.
AB  - : Antihypertensive, lipid lowering, antidiabetic and antiplatelet treatments all
      substantially reduce the risk of cardiovascular morbid and fatal events. In real
      life, however, effective implementation of these treatments is rare, and thus
      their contribution to cardiovascular prevention is much less than it could be,
      based on research data. This article reviews the pros and cons of cardiovascular
      prevention by the polypill approach. It is argued that the high prevalence of
      individuals with a multifactorial risk profile provides a strong rationale for a
      therapeutic strategy based on the combination in a single tablet of drugs against
      different risk factors. It is further argued that other important favourable
      arguments exist. First, in real-life adherence to all above treatments is very
      low, leading to a major increase in the incidence and risk of cardiovascular
      outcomes. Second, although a large number of factors are involved, adherence is
      adversely affected by the complexity of the prescribed treatment regimen and can
      be considerably improved by treatment simplification. Third, recent studies in
      patients with a history of manifest cardiovascular disease have documented that
      different cardiovascular drugs can be combined in a single tablet with no loss of
      their individual efficacy or unexpected inconveniences and this does favour
      adherence to treatment and multiple risk factor control, supporting use of the
      polypill in secondary cardiovascular prevention. It is finally also mentioned,
      however, that the polypill may have some drawbacks and that at present no
      evidence is available that this approach reduces cardiovascular outcome to a
      greater degree than standard treatment strategies. Trials are under way to
      provide an answer to this question and thus allow the therapeutic value of this
      approach to be known.

PMID- 28448292
TI  - Show Back: Developing and Testing of a Simulation-Based Assessment Method for
      Identifying Problems in Self-Management of Medications in Older Adults.

PMID- 28448293
TI  - Trabeculectomy or Transscleral Cyclophotocoagulation as Initial Treatment of
      Secondary Childhood Glaucoma in Northern Tanzania.
AB  - PURPOSE: The purpose is to describe the outcome of trabeculectomy with
      transscleral cyclophotocoagulation (TSCPC) as an initial intervention for
      secondary childhood glaucoma in Northern Tanzania. METHODS: A retrospective,
      consecutive case series was analyzed of all children with secondary childhood
      glaucoma who underwent initial trabeculectomy or TSCPC between 2000 and 2013 at a
      referral eye unit in Northern Tanzania. Retrospective data were collected on
      causes of glaucoma, intraocular pressure (IOP), visual acuity, complications, and
      subsequent interventions. Outcomes were evaluated using Kaplan-Meier survival
      analysis and compared with Cox regression analysis. The main outcome measure was
      failure (IOP>21 mm Hg). RESULTS: Thirty-six eyes of 27 children (male, 21; median
      age, 9 y; range, 0.3 to 15 y) with secondary childhood glaucoma underwent
      trabeculectomy (19 eyes, 53%) or TSCPC (17 eyes, 47%). Causes included ocular
      trauma (13, 36%), previous cataract surgery (12, 33%), congenital aniridia (5,
      14%), Sturge-Weber syndrome (2, 6%), steroid-induced glaucoma (2, 6%), uveitis
      (1, 3%), and unspecified leucoma (1, 3%). After 12 months, success was achieved
      in 48% after trabeculectomy and 18% after TSCPC, with visual acuity remaining
      unchanged in 11 of 14 (79%) and 4 of 5 eyes (80%), respectively. One third of the
      children did not return for follow-up after 1 year. Distance to the hospital
      (>100 km) was a significant risk factor for trabeculectomy failure (P=0.031).
      CONCLUSIONS: A high proportion of secondary childhood glaucoma in Northern
      Tanzania was caused by trauma and previous cataract surgery. Trabeculectomy was
      associated with better IOP control but also a higher complication rate. The
      ability to maintain visual function was comparable after both interventions.
      Failure was associated with a journey to the eye hospital (>100 km) possibly
      leading to late presentation with advanced disease and erratic follow-up.

PMID- 28448294
TI  - Macular Ganglion Cell and Retinal Nerve Fiber Layer Thickness in Children With
      Refractive Errors-An Optical Coherence Tomography Study.
AB  - PURPOSE: To study the distribution of macular ganglion cell-inner plexiform layer
      (GC-IPL) thickness and peripapillary retinal nerve fiber layer (RNFL) thickness
      in children with refractive errors. MATERIALS AND METHODS: Two hundred forty
      three healthy eyes from 139 children with refractive error ranging from -10.00 to
      +5.00 D were recruited from the National University Hospital Eye Surgery
      outpatient clinic. After a comprehensive ocular examination, refraction, and
      axial length (AL) measurement (IOLMaster), macular GC-IPL and RNFL thickness
      values were obtained with a spectral domain Cirrus high definition optical
      coherence tomography system (Carl Zeiss Meditec Inc.). Only scans with signal
      strength of >6/10 were included. Correlation between variables was calculated
      using the Pearson correlation coefficient. A multivariate analysis using mixed
      models was done to adjust for confounders. RESULTS: The mean spherical equivalent
      refraction was -3.20+/-3.51 D and mean AL was 24.39+/-1.72 mm. Average, minimum,
      superior, and inferior GC-IPL were 82.59+/-6.29, 77.17+/-9.65, 83.68+/-6.96, and
      81.64+/-6.70 MUm, respectively. Average, superior, and inferior peripapillary
      RNFL were 99.00+/-11.45, 123.20+/-25.81, and 124.24+/-22.23 MUm, respectively.
      Average, superior, and inferior GC-IPL were correlated with AL (beta=-2.056, P
      value 0.000; beta=-2.383, P-value 0.000; beta=-1.721, P-value 0.000), but minimum
      GC-IPL was not (beta=-1.056, P-value 0.115). None of the RNFL parameters were
      correlated with AL. CONCLUSIONS: This study establishes normative macular GC-IPL
      and RNFL thickness in children with refractive errors. Our results suggest that
      high definition optical coherence tomography RNFL parameters and minimum GC-IPL
      are not affected by AL or myopia in children, and therefore warrants further
      evaluation in pediatric glaucoma patients.

PMID- 28448296
TI  - The Use of the MolecuLight i:X in Managing Burns: A Pilot Study.
AB  - The MolecuLight i:X Imaging Device is a portable, noninvasive, real-time camera
      used to visualize the bacterial load in a wound. It uses violet light
      illumination and a dual bandpass optical filter to capture the fluorescence of
      endogenous structures in the tissue matrix and harmful bacteria. The MolecuLight
      i:X captures images of wounds and highlights potentially detrimental levels of
      bacteria. This is an initial evaluation of using the MolecuLight i:X camera in
      the management of burns to demonstrate the following: the ability of the device
      to guide clinicians in their management of the burn (ie, detect, identify, and
      specify swabbing locations). Burn wounds were photographed under standard light
      and violet light illumination to compare presentations of obvious infection signs
      and symptoms. Microbiology swab samples were obtained to correlate any bacterial
      presence to the images. The fluorescence images were used to guide swabs to where
      the bacteria were congregating. Twenty patients were imaged. Four patients did
      not have bacterial contamination based on their images and swab results. Sixteen
      patients showed growth of Staphylococcus aureus, Pseudomonas aeruginosa, or other
      bacteria. Nine of the patients, by definition, had infections. These findings
      were correlated with the typical signs and symptoms of infection, the
      fluorescence images, and the microbiology results. The efficacy of the
      MolecuLight i:X is evident due to the microbiology results correlating to the
      images. Further research is being done to test the device in terms of being an
      early intervention tool. With these early results and guidance of swab samples,
      the MolecuLight i:X may be able to detect bacterial load before an infection and
      subsequent graft failure, thereby shortening lengths of hospital stay and
      improving overall healing.

PMID- 28448295
TI  - The Role of Mitochondrial Stress in Muscle Wasting Following Severe Burn Trauma.
AB  - Increased resting metabolic rate and skeletal muscle wasting are hallmarks of the
      pathophysiological stress response to severe burn trauma. However, whether these
      two responses occur independently in burn patients or are in fact related remains
      unclear. In light of recent evidence demonstrating that increased proteolysis in
      skeletal muscle of burned patients is accompanied by mitochondrial
      hypermetabolism, oxidative stress, and protein damage; in this article, we
      discuss the evidence for a role for the mitochondrion in skeletal muscle wasting
      following severe burn trauma. In particular, we focus on the role of
      mitochondrial superoxide production in oxidative stress and subsequent
      proteolysis, and discuss the role of the mitochondrion as a signaling organelle
      resulting in protein catabolism in other cellular compartments following severe
      burn trauma.

PMID- 28448297
TI  - The Fate of Chronic Burn Wounds Suspected as Marjolin's Ulcers.
AB  - Marjolin's ulcer is the malignant transformation of chronic nonhealing ulcers
      that have developed in burn scars or in any other chronic wound. Development of
      this malignancy tends to be slow and insidious, but it becomes more aggressive
      when the Marjolin's ulcer breaks free of the scar. We reviewed 24 cases of
      patients who complained of chronic burn wounds suspected to be Marjolin's ulcers.
      Histologically, chronic ulcer and pseudoepitheliomatous hyperplasia were 21%,
      respectively, and malignancy, including squamous cell carcinoma and
      leiomyosarcoma, were 58%. The mean latency period was 31.6 +/- 13.0 years, and
      the majority of lesions occurred in the extremities. Pseudoepitheliomatous
      hyperplasia in chronic burn wounds, which is difficult to distinguish from
      squamous cell carcinoma and considered as a transitional state to becoming a
      malignant tumor, should be treated as a malignancy. An aggressive excision and
      reconstruction with free tissue transfer or regional flap transposition should be
      adopted for adequate ablation and definitive coverage, rather than skin graft and
      regular surveillance.

PMID- 28448298
TI  - Anesthetic consideration for neuromuscular diseases.
AB  - PURPOSE OF REVIEW: The aim of this review is to examine data relating to
      perioperative management of the patient with neuromuscular disorders RECENT
      FINDINGS: Patients with pre-existing neuromuscular disorders are at risk for a
      number of postoperative complications that are related to anesthetic drugs that
      are administered intraoperatively. Careful preoperative assessment is necessary
      to reduce morbidity and mortality. In particular, the risk of postoperative
      respiratory failure and need for long-term ventilation should be reviewed with
      patients. The use of succinylcholine should be avoided in muscular dystrophies,
      motor neuron diseases, and intrinsic muscle disease due to a risk of malignant
      hyperthermia, hyperkalemia, rhabdomyolysis, and cardiac arrest. The use of
      quantitative neuromuscular monitoring should be strongly considered whenever
      nondepolarizing neuromuscular blocking agents are administered. A number of case
      series and reports have been recently published demonstrating that sugammadex can
      be safely used in patients with neuromuscular disease; the risk of residual
      neuromuscular is nearly eliminated when this agent is administered
      intraoperatively. SUMMARY: Careful assessment and management of patients with
      underlying neuromuscular diseases is required to reduce postoperative
      complications. This article reviews the anesthetic implications of patients
      undergoing surgery with neuromuscular disorder.

PMID- 28448299
TI  - Impact of Interruptions, Distractions, and Cognitive Load on Procedure Failures
      and Medication Administration Errors.
AB  - Medication administration errors are difficult to intercept since they occur at
      the end of the process. The study describes interruptions, distractions, and
      cognitive load experienced by registered nurses during medication administration
      and explores their impact on procedure failures and medication administration
      errors. The focus of this study was unique as it investigated how known
      individual and environmental factors interacted and culminated in errors.

PMID- 28448300
TI  - Assessment of the Quality of Nursing Care From Perspectives of Nurses Who
      Experienced Hospitalization as Patients.
AB  - Nurses as patients or caregivers evaluated their care differently than nonnurses.
      A qualitative design with content analysis was used to provide an assessment of
      the quality of nursing care by examining nurses' perceptions as recipients of
      care. The 231 participants were registered nurses recruited from 8 hospitals in
      Amman, Jordan. Participants evaluated the quality of nursing care as either high
      (29.5%) or low (70.5%). Four improvement themes emerged: improving competency,
      serve with caring, professionalism, and administrative factors.

PMID- 28448301
TI  - Patients' Experience After a Fall and Their Perceptions of Fall Prevention: A
      Qualitative Study.
AB  - An exploratory descriptive study was conducted to explore the perspectives of
      patients who had fallen in the hospital; 100 patients were interviewed. An
      inductive content analysis approach was adopted. Six themes emerged: Apathetic
      toward falls, self-blame behavior, reluctance to impose on busy nurses, negative
      feelings toward nurses, overestimating own ability, and poor retention of
      information. Patients often downplayed the risks of falls and were reluctant to
      call for help.

PMID- 28448302
TI  - QSEN Institute RN-BSN Task Force: White Paper on Recommendation for Systems-Based
      Practice Competency.
AB  - The Quality and Safety Education for Nurses (QSEN) Institute RN-BSN Task Force
      presents a white paper on Recommendation for a Systems-based Practice Competency.
      The task force proposes a seventh QSEN competency, systems-based practice, to
      improve patient quality and safety. Recommendations to integrate systems-based
      practice into both education and practice settings, consistent with job
      descriptions and promotion criteria, involve a comprehensive continuing education
      program for nurses upon interview, orientation, residency programming,
      performance evaluation, and license renewal.

PMID- 28448303
TI  - Predictability of Interruptions During Medication Administration With Related
      Behavioral Management Strategies.
AB  - The aim of this qualitative study was to examine the nature of interruptions
      during medication administration. Focus groups were conducted with
      medical/surgical nurses (n = 15), critical care nurses (n = 13), and nurse
      managers/educators/specialists (n = 6). Most interruptions (78%) were
      predictable. Nurse-adopted strategies included blocking, engaging, mediating,
      multitasking, and preventing. Educational content was developed that relates
      behavioral strategies to respond to predictable and unpredictable interruptions.

PMID- 28448304
TI  - Systematic Review and Network Meta-Analysis of Bevacizumab Plus First-Line
      Topotecan-Paclitaxel or Cisplatin-Paclitaxel Versus Non-Bevacizumab-Containing
      Therapies in Persistent, Recurrent, or Metastatic Cervical Cancer.
AB  - OBJECTIVE: Despite advances in cervical cancer prevention and diagnosis, outcomes
      for patients given a diagnosis of advanced and recurrent disease are poor. In the
      GOG240 trial, the addition of bevacizumab to paclitaxel-topotecan or paclitaxel
      cisplatin has been shown to prolong survival compared with paclitaxel-topotecan
      or paclitaxel-cisplatin in patients with persistent, recurrent, or metastatic
      disease. However, standards of care vary between regions and countries. The
      purpose of this systematic review and network meta-analysis was to enable a
      comparison between bevacizumab + chemotherapy with multiple monotherapy or
      combination chemotherapy regimens in the treatment for women with advanced,
      recurrent, or persistent cervical cancer. METHODS/MATERIALS: A systematic
      literature review was conducted to identify randomized or nonrandomized
      controlled trials of patients with recurrent, persistent, or metastatic cervical
      cancer published in English from 1999 to 2015. A feasibility study was performed
      to assess the heterogeneity of the trials, and a network meta-analysis was
      conducted. Fixed- and random-effects models were fitted to calculate the hazard
      ratio for overall survival (OS) for all pairwise comparisons and ranking of all
      interventions. RESULTS: Twenty-three studies (19 trials) met inclusion criteria
      and were included in the review. Sample sizes ranged from 69 to 452, and median
      patient age ranged from 45 to 53 years. There was a trend toward prolonged OS
      with cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab
      compared with all non-bevacizumab-containing therapies. Cisplatin-paclitaxel
      bevacizumab had the highest probability of being the most efficacious compared
      with all regimens (68.1%), and cisplatin monotherapy had the lowest (0%).
      CONCLUSIONS: The results of this network meta-analysis show that bevacizumab in
      combination with paclitaxel-topotecan or paclitaxel-cisplatin is likely to
      prolong OS over other non-bevacizumab-containing chemotherapies (eg, paclitaxel
      carboplatin), which were not included in the GOG240 trial. In patients with
      advanced, persistent, and recurrent cervical cancer, cisplatin-paclitaxel
      bevacizumab and topotecan-paclitaxel-bevacizumab showed the highest efficacy in
      all regimens investigated in this analysis.

PMID- 28448305
TI  - Possible Risk Factors of Pulmonary Metastases in Patients With International
      Federation of Gynecology and Obstetrics Stage I Endometrioid-Type Endometrial
      Cancer.
AB  - OBJECTIVE: Limited data have been obtained in regard to pulmonary metastasis (PM)
      in patients with stage I endometrial cancer. The aims of the study were (1) to
      present the clinical and pathological characteristics of patients with PM in the
      setting of stage I endometrioid-type endometrial cancer (EEC) and (2) to define
      possible factors that may be used to predict PM. METHODS: Six hundred thirty
      patients with stage I EEC, including 12 with PM, 19 with extra-PM (EPM), and 599
      with no recurrence, were observed. Paired samples of primary and metastatic
      tumors from a patient were used for exome sequencing to identify potential gene
      mutations associated with PM. RESULTS: There was no significant difference in the
      age, Ki-67, lymphatic vascular space invasion, and grade 3 among the 3 groups (P
      > 0.05). More squamous epithelial differentiation was observed in PM (7/12), as
      compared with patients with EPM (1/19) (P < 0.05) and no recurrence (20/599) (P <
      0.05). The tumor size of the patients with PM was bigger than that of
      nonrecurrent patients (29.8 +/- 16.6 vs 18.5 +/- 16.3 mm, P < 0.05). More
      percentage of patients with deep myometrial invasion (IB) were found in PM (6/12)
      (P < 0.05) as compared with patients with EPM (3/19) (P < 0.05) and no recurrence
      (76/599). CDH10, ARID1A, and EMT-associated gene mutations were identified in
      metastatic tumor tissue but not in primary tumors from a patient with EEC and
      lung metastases. CONCLUSIONS: Squamous epithelial differentiation, large tumor
      size, and deep myometrial invasion might be risk factors for PM in patients with
      stage I EEC. CDH10, ARID1A, and EMT-associated gene mutation may promote the
      initiation of lung recurrence. However, further studies are needed to determine
      the precise mechanisms associated with lung metastasis in these patients.

PMID- 28448306
TI  - Open Glenohumeral Joint Reduction and Latissimus Dorsi and Teres Major Tendon
      Transfers for Infants and Children Following Brachial Plexus Birth Palsy.
AB  - Glenohumeral dysplasia can occur in brachial plexus birth palsy due to an
      imbalance of muscle forces. Most commonly this occurs in C5-C6 injuries where the
      shoulder external rotators are weak compared with the shoulder internal rotators.
      Treatment of the dysplasia with open reduction of the glenohumeral joint in
      combination with rebalancing the muscles can improve the development of the
      joint. Furthermore, the tendon transfer can improve shoulder function by
      decreasing the internal rotation forces about the shoulder while increasing the
      external rotation forces. This paper describes the indications,
      contraindications, and technique of performing an open glenohumeral joint
      reduction and latissimus dorsi and teres major tendon transfers for brachial
      plexus birth palsy.

PMID- 28448307
TI  - Explaining performance in health care: How and when top management competencies
      make the difference.
AB  - BACKGROUND: One of the most distinctive management competencies is related to the
      ability to structure the strategic vision, develop long-term plans, and
      communicate them efficiently to the employees in order to empower them to enact.
      These managerial competencies in complex organizations are strongly related to
      the capacity to engage professionals as a predictor of high-performing
      organizations. PURPOSE: The aim of this study was to investigate the relationship
      between top management competencies, information sharing, and organizational
      performance in public health care system and to look at the management role in
      assuring information sharing on organizational strategies to achieve
      professionals' engagement. METHODOLOGY/APPROACH: This relationship is empirically
      tested using the longitudinal data of public health care organizations from the
      Tuscany Region (Italy). The top management competencies and information sharing
      are evaluated by the heads of the departments. While information sharing refers
      to the organizational level (e.g., to convey the objectives), managerial
      competencies refer to the individual level (e.g., to manage conflict). A random
      effect regression model is estimated using average responses by the health
      organization. Data come from the multidimensional performance evaluation system
      (2008 to 2014 years). RESULTS: Findings show that managerial competencies are
      positively associated to organizational performance. Moreover, managerial
      competencies are strongly linked to the information sharing process developed
      into the organizations. In particular, managerial competencies play a significant
      role on whole performance, and results are mediated by the use of mature
      information sharing instruments such as benchmarking of performance results.
      CONCLUSION: Systematic information sharing process regarding performance results,
      goals, and organizational structure provided by top management seems an effective
      strategy to engage professionals. Control variables suggest that top management
      tenure and turnover do not have an effect, whereas bigger health care
      organizations seem to negatively influence this relation. PRACTICE IMPLICATIONS:
      Information sharing is the basis for clinicians' engagement and adds value to
      organizational performance.This is an open-access article distributed under the
      terms of the Creative Commons Attribution-Non Commercial-No Derivatives License
      4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided
      it is properly cited. The work cannot be changed in any way or used commercially
      without permission from the journal.

PMID- 28448308
TI  - The Effects of Prenatal Maternal Stress on Early Temperament: The 2011 Queensland
      Flood Study.
AB  - OBJECTIVE: This study examined the effects of disaster-related prenatal maternal
      stress on infant temperament and whether the sex of the infant or the timing of
      the stressor in pregnancy would moderate the effects. METHODS: Mothers' objective
      experiences of a sudden-onset flood in Queensland, Australia, their subjective
      emotional reactions, and cognitive appraisal of the event were assessed. At 6
      months postpartum, 121 mothers reported their infant's temperament on the 5
      dimensions of the Short Temperament Scale for Infants. RESULTS: When controlling
      for postnatal maternal factors, subjective prenatal maternal stress and cognitive
      appraisal of the disaster were associated with easier aspects of infant
      temperament. However, several interesting interactions emerged showing negative
      effects of the flood. With higher levels of objective hardship in pregnancy, boys
      (but not girls) received more irritable temperament ratings. When the flood
      occurred early in pregnancy, higher levels of objective hardship predicted more
      arrhythmic infant temperament. Finally, mothers whose emotional response to the
      flood exceeded the hardship they endured reported significantly more active
      reactive infants. CONCLUSION: Prenatal maternal stress from a natural disaster
      predicted more difficult temperament ratings that were moderated by infant sex,
      timing of the flood in gestation, and mother's emotional response to the
      disaster.

PMID- 28448309
TI  - Clinical Feasibility of 3-Dimensional Magnetic Resonance Cholangiopancreatography
      Using Compressed Sensing: Comparison of Image Quality and Diagnostic Performance.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical feasibility of fast
      3-dimensional (3D) magnetic resonance cholangiopancreatography (MRCP) using
      compressed sensing (CS) in comparison with conventional navigator-triggered 3D
      MRCP. MATERIALS AND METHODS: This retrospective study was approved by our
      institutional review board, and the requirement of informed consent was waived. A
      total of 84 patients (male-to-female ratio, 41:43; mean age, 47.3 +/- 18.8 years)
      who underwent conventional 3D navigator-triggered T2-weighted MRCP using sampling
      perfection with application optimized contrasts (SPACE) and fast 3D MRCP using
      SPACE with high undersampling combined with CS reconstruction (CS SPACE; CS-MRCP)
      on a 3 T scanner were included. Among them, 28 patients additionally underwent 3D
      breath-hold CS-MRCP (BH-CS-MRCP) with 5.7% k-space sampling. Three board
      certified radiologists then independently reviewed the examinations for bile duct
      and pancreatic duct visualization and overall image quality on a 5-point scale,
      and image sharpness and background suppression on a 4-point scale, with the
      higher score indicating better image quality. In addition, diagnostic performance
      for the detection of anatomic variation and diseases of the bile duct, and
      pancreatic disease were assessed on a per-patient basis in the subgroup of 28
      patients who underwent conventional MRCP, CS-MRCP, and BH-CS-MRCP in the same
      manner. RESULTS: Mean acquisition times of conventional MRCP, CS-MRCP, and BH-CS
      MRCP were 7 minutes (419.7 seconds), 3 minutes 47 seconds (227.0 seconds), and 16
      seconds, respectively (P < 0.0001, in all comparisons). In all patients, CS-MRCP
      showed better image sharpness (3.54 +/- 0.60 vs 3.37 +/- 0.75, P = 0.04) and
      visualization of the common bile duct (4.55 +/- 0.60 vs 4.39 +/- 0.78, P = 0.034)
      and pancreatic duct (3.47 +/- 1.22 vs 3.26 +/- 1.32, P = 0.025), but lower
      background suppression (3.00 +/- 0.54 vs 3.37 +/- 0.58, P < 0.001) than
      conventional MRCP. Overall image quality was not significantly different between
      the 2 examinations (3.51 +/- 0.95 vs 3.47 +/- 1.09, P = 0.75). The number of
      indeterminate MRCP examinations for the anatomic variation and disease of the
      bile duct significantly decreased on CS-MRCP, from 16.7%-22.6% to 9.5%-11.9% and
      8.4%-15.6% to 3.6%-8.4% in all readers (P = 0.003-0.03). In the 28 patients who
      underwent BH-CS-MRCP, better image quality was demonstrated than with
      conventional MRCP and CS-MRCP (4.10 +/- 0.84 vs 3.44 +/- 1.21 vs 3.50 +/- 1.11,
      respectively, P = 0.002, 0.001). Sensitivities for detecting bile duct disease
      was 88.9% to 100% on both BH-CS-MRCP and conventional MRCP (P > 0.05), and for
      detecting pancreatic disease was 66.7% to 83.3% on BH-CS-MRCP and 50.0% to 72.2%
      on conventional MRCP (P = 0.002 in reader 1, 0.06-0.47 in readers 2-3).
      CONCLUSIONS: Compressed sensing MRCP using incoherent undersampling combined with
      CS reconstruction provided comparable image quality to conventional MRCP while
      reducing the acquisition time to within a single breath-hold (16 seconds).

PMID- 28448310
TI  - Comparison of Power Versus Manual Injection in Bolus Shape and Image Quality on
      Contrast-Enhanced Magnetic Resonance Angiography: An Experimental Study in a
      Swine Model.
AB  - OBJECTIVE: The aim of this study was to compare power versus manual injection in
      bolus shape and image quality on contrast-enhanced magnetic resonance angiography
      (CE-MRA). MATERIALS AND METHODS: Three types of CE-MRA (head-neck 3-dimensional
      [3D] MRA with a test-bolus technique, thoracic-abdominal 3D MRA with a bolus
      tracking technique, and thoracic-abdominal time-resolved 4-dimensional [4D] MRA)
      were performed after power and manual injection of gadobutrol (0.1 mmol/kg) at 2
      mL/s in 12 pigs (6 sets of power and manual injections for each type of CE-MRA).
      For the quantitative analysis, the signal-to-noise ratio was measured on
      ascending aorta, descending aorta, brachiocephalic trunk, common carotid artery,
      and external carotid artery on the 6 sets of head-neck 3D MRA, and on ascending
      aorta, descending aorta, brachiocephalic trunk, abdominal aorta, celiac trunk,
      and renal artery on the 6 sets of thoracic-abdominal 3D MRA. Bolus shapes were
      evaluated on the 6 sets each of test-bolus scans and 4D MRA. For the qualitative
      analysis, arterial enhancement, superimposition of nontargeted enhancement, and
      overall image quality were evaluated on 3D MRA. Visibility of bolus transition
      was assessed on 4D MRA. Intraindividual comparison between power and manual
      injection was made by paired t test, Wilcoxon rank sum test, and analysis of
      variance by ranks. RESULTS: Signal-to-noise ratio on 3D MRA was statistically
      higher with power injection than with manual injection (P < 0.001). Bolus shapes
      (test-bolus, 4D MRA) were represented by a characteristic standard bolus curve
      (sharp first-pass peak followed by a gentle recirculation peak) in all the 12
      scans with power injection, but only in 1 of the 12 scans with manual injection.
      Standard deviations of time-to-peak enhancement were smaller in power injection
      than in manual injection. Qualitatively, although both injection methods achieved
      diagnostic quality on 3D MRA, power injection exhibited significantly higher
      image quality than manual injection (P = 0.001) due to significantly higher
      arterial enhancement (P = 0.031) and less superimposition of nontargeted
      enhancement (P = 0.001). Visibility of bolus transition on 4D MRA was
      significantly better with power injection than with manual injection (P = 0.031).
      CONCLUSIONS: Compared with manual injection, power injection provides more
      standardized bolus shapes and higher image quality due to higher arterial
      enhancement and less superimposition of nontargeted vessels.

PMID- 28448312
TI  - Simple Mohs Reconstruction in a Blistering Disorder Patient.

PMID- 28448313
TI  - Commentary on A 30-Minute, Monthly, Live, Webinar-Based Journal Club Activity
      Alters the Self-Reported Behaviors of Dermatologic Surgeons.

PMID- 28448314
TI  - A 30-Minute, Monthly, Live, Webinar-Based Journal Club Activity Alters the Self
      Reported Behaviors of Dermatologic Surgeons.
AB  - BACKGROUND: Journal clubs provide a way to communicate advances in recent
      literature. In outpatient surgical subspecialties, such as dermatologic surgery,
      physicians may face challenges in finding or attending meetings pertinent to
      their practice. OBJECTIVE: To assess the utility of a live web-based journal club
      in dermatologic surgery. MATERIALS AND METHODS: Monthly 30-minute journal club
      sessions covering 5 to 6 scholarly articles. Anonymous surveys were used to
      evaluate the utility and self-reported learning associated with each meeting.
      RESULTS: From December 2012 to February 2015, 117 articles were reviewed. Survey
      data were acquired monthly, apart from 5 months of missing data. On average, the
      survey response rate was 37% (range: 7%-82%), with an average of 17 participants
      per monthly session (range: 9-25). The mean monthly usefulness score was 83.7
      (101-point scale), with participants scoring their likelihood of returning in the
      future as 96.2 (0 = not likely, 100 = extremely likely). At each session, a mean
      of 68% of participants felt that at least one article would change their practice
      of medicine. CONCLUSION: A monthly online and telephonic journal club may be a
      practical and effective way to inform dermatologic surgeons of new developments
      in high impact literature and may influence improvements in individual practice.

PMID- 28448317
TI  - Early Experience in 100 Consecutive Patients With Injection Adipocytolysis for
      Neck Contouring With ATX-101 (Deoxycholic Acid).
AB  - BACKGROUND: Deoxycholic acid (DCA) is approved for improvement in the appearance
      of moderate to severe convexity or fullness associated with submental fat.
      OBJECTIVE: To assess early treatment experience with DCA injection in a clinical
      practice setting. MATERIALS AND METHODS: In this single-center, prospective,
      single-arm, observational study, 100 consecutive patients seeking to decrease
      submental fullness received subcutaneous DCA (2 mg/cm) injections in the
      submental area (maximum of 6 sessions at >=1 month intervals). Treatment response
      was assessed 1 and 5 to 7 weeks posttreatment using the clinician-reported
      submental fat rating scale (CR-SMFRS) and retrospective independent photograph
      review by 2 physicians. RESULTS: Overall, 100 patients had 152 treatment sessions
      (58, 33, 8, and 1 patients had 1, 2, 3, and 4 sessions, respectively). CR-SMFRS
      score improved by >=1 point from baseline in 88 (88%) patients; of these, 46, 33,
      8, and 1 patients had 1, 2, 3, and 4 sessions, respectively. Local edema,
      numbness, and tenderness were reported for a mean (SD) of 7.7 (5.3), 28.5 (11.4),
      and 3.5 (3.5) days, respectively. Two patients experienced marginal mandibular
      nerve paresis. CONCLUSION: Deoxycholic acid injection, a minimally invasive
      procedure for neck contouring, was effective and generally well tolerated in the
      private practice setting.

PMID- 28448319
TI  - Tranexamic acid reduces blood loss and transfusion requirements in primary
      simultaneous bilateral total knee arthroplasty: a meta-analysis of randomized
      controlled trials.
AB  - : The aim of this meta-analysis is to assess the effectiveness and safety of
      intravenous application tranexamic acid (TXA) in primary simultaneous bilateral
      total knee arthroplasty (TKA). We searched electronic databases including PubMed,
      Embase, the Web of Science, the Cochrane Library and the Google Scholar, for
      published studies involving the intravenous application TXA in primary
      simultaneous bilateral TKA. All randomized controlled trials were included. The
      focus of the meta-analysis was on the outcomes of total blood loss, drainage
      volume, transfusion requirements and deep venous thrombosis (DVT) and/or
      pulmonary embolism. The relevant data were analyzed using RevMan 5.2. Six high
      randomized controlled trials were included, with a total sample size of 394
      patients. The intravenous application of TXA significantly reduced total blood
      loss [95% confidence interval (CI), -519.52 to -126.40; P = 0.001], drainage
      volume (95% CI, -551.76 to -138.57; P = 0.001) and transfusion requirements (risk
      ratio, 0.38; 95% CI, 0.21-0.68; P = 0.001) compared with the control group. In
      addition, there were no significant differences in the rate of DVT (P = 1.00)
      and/or pulmonary embolism between the two groups. Based on the current evidence,
      this meta-analysis showed that intravenous application of TXA is effective and a
      well tolerated treatment to reduce total blood loss, drainage volume and
      transfusion requirements without increasing the risk of DVT and/or pulmonary
      embolism in primary simultaneous bilateral TKA.

PMID- 28448318
TI  - Two-State Collaborative Study of a Multifaceted Intervention to Decrease
      Ventilator-Associated Events.
AB  - OBJECTIVES: Ventilator-associated events are associated with increased mortality,
      prolonged mechanical ventilation, and longer ICU stay. Given strong national
      interest in improving ventilated patient care, the National Institute of Health
      and Agency for Healthcare Research and Quality funded a two-state collaborative
      to reduce ventilator-associated events. We describe the collaborative's impact on
      ventilator-associated event rates in 56 ICUs. DESIGN: Longitudinal quasi
      experimental study. SETTING: Fifty-six ICUs at 38 hospitals in Maryland and
      Pennsylvania from October 2012 to March 2015. INTERVENTIONS: We organized a
      multifaceted intervention to improve adherence with evidence-based practices,
      unit teamwork, and safety culture. Evidence-based interventions promoted by the
      collaborative included head-of-bed elevation, use of subglottic secretion
      drainage endotracheal tubes, oral care, chlorhexidine mouth care, and daily
      spontaneous awakening and breathing trials. Each unit established a
      multidisciplinary quality improvement team. We coached teams to establish
      comprehensive unit-based safety programs through monthly teleconferences. Data
      were collected on rounds using a common tool and entered into a Web-based portal.
      MEASUREMENTS AND RESULTS: ICUs reported 69,417 ventilated patient-days of
      intervention compliance observations and 1,022 unit-months of ventilator
      associated event data. Compliance with all evidence-based interventions improved
      over the course of the collaborative. The quarterly mean ventilator-associated
      event rate significantly decreased from 7.34 to 4.58 cases per 1,000 ventilator
      days after 24 months of implementation (p = 0.007). During the same time period,
      infection-related ventilator-associated complication and possible and probable
      ventilator-associated pneumonia rates decreased from 3.15 to 1.56 and 1.41 to
      0.31 cases per 1,000 ventilator-days (p = 0.018, p = 0.012), respectively.
      CONCLUSIONS: A multifaceted intervention was associated with improved compliance
      with evidence-based interventions and decreases in ventilator-associated event,
      infection-related ventilator-associated complication, and probable ventilator
      associated pneumonia. Our study is the largest to date affirming that best
      practices can prevent ventilator-associated events.

PMID- 28448320
TI  - Difficult Airway Management Caused by Local Anesthetic Allergy During Emergent
      Cesarean Delivery: A Case Report.
AB  - Difficult airway management in the gravid patient is a well-described phenomenon.
      We present a case of emergent cesarean delivery complicated by a "cannot
      intubate, cannot ventilate" scenario that was later determined to be secondary to
      an allergic, IgE-mediated reaction to epidurally administered local anesthetic.

PMID- 28448321
TI  - Chest Pain During Cesarean Delivery in Relation to Anomalous Right Coronary
      Artery: A Case Report.
AB  - Chest pain during labor can have many etiologies, one of which is myocardial
      ischemia. We report a 38-year-old woman with American Society of Anesthesiology
      physical status I scheduled for elective cesarean delivery who experienced chest
      pain and electrocardiographic signs of myocardial ischemia immediately after
      carbetocin administration. Subsequent investigations revealed an aberrant right
      coronary artery originating from the left coronary sinus coursing between the
      aorta and the pulmonary artery. This was considered the likely cause of the
      patient's chest pain. The patient gave written permission for the authors to
      publish this report.

PMID- 28448322
TI  - Dexmedetomidine as a Rescue Therapy for Emergence Delirium in Adults: A Case
      Series.
AB  - Emergence delirium (ED) in adult patients encountered in the postanesthesia care
      unit (PACU) is not well studied; nor are ED treatment strategies. Similar to
      delirium in the intensive care unit, ED in the PACU can result in serious
      complications. We describe 3 cases of ED in the PACU in patients with a history
      of posttraumatic stress disorder who were successfully treated with
      dexmedetomidine. Although likely utilized more frequently in recent years, the
      use of dexmedetomidine in the PACU for treatment of ED is not established in the
      literature. Further research regarding treatment of ED in adults is necessary,
      allowing for optimization of patient care and improvement in patient outcomes.

PMID- 28448323
TI  - Hyperkalemia After Laparoscopic Nephrectomy in Patients With Renal Insufficiency:
      A Case Report.
AB  - Laparoscopic surgery is an evolving surgical modality in children, which has been
      applied to increasingly more complex surgeries and patients, including patients
      with renal insufficiency. These patients are particularly susceptible to the
      challenges that laparoscopy imposes on their altered physiology, leading to
      marked electrolyte disturbances, including metabolic acidosis and hyperkalemia.
      Hyperkalemia has the potential for marked impairment of cardiac conduction. We
      report 2 cases where significant, potentially lethal hyperkalemia developed
      during laparoscopic nephrectomy in adolescents with renal insufficiency.
      Awareness of this issue, as well as adequate preparation and intraoperative
      monitoring are essential to preventing this life-threatening complication.

PMID- 28448324
TI  - Intraoperative Use of the Ventrain for Single Lung Ventilation After Iatrogenic
      Trauma to the Left Main Bronchus During Thoracoscopy: A Case Report.
AB  - In a patient undergoing thoracoscopic esophagectomy and concomitant wedge
      resection, an iatrogenic lesion in the left main bronchus was observed following
      deflation of the right lung. Because the bronchial cuff of the double-lumen tube
      was visible through the lesion, repair was only possible after deflation of the
      bulging cuff. Positive pressure ventilation would result in air leakage
      jeopardizing ventilation and oxygenation. This challenging situation was resolved
      using the Ventrain device to oxygenate the patient through a small-bore catheter
      placed through the lumen beyond the bronchial defect. With the use of this
      technique, oxygenation was maintained at an acceptable level during repair.

PMID- 28448325
TI  - Combined Spinal-Epidural Anesthesia With Dexmedetomidine-Based Sedation for
      Multiple Corrective Osteotomies in a Child With Osteogenesis Imperfecta Type III:
      A Case Report.
AB  - Osteogenesis imperfecta (OI) is a rare disabling genetic connective tissue
      disorder. General anesthesia in these patients is associated with increased
      risks. Regional anesthesia is favored wherever feasible, but there are limited
      reports of use of a sole regional technique in OI in pediatric patients.
      Moreover, combined spinal-epidural anesthesia has never been described
      previously. We are reporting the use of combined spinal-epidural anesthesia for a
      prolonged surgery (multiple osteotomies) of lower limbs in a 10-year-old
      wheelchair-bound child with OI type III. Preoperative counseling, ultrasonography
      guidance, titrated local anesthetic dosage, and dexmedetomidine sedation helped
      establish optimum surgical conditions.

PMID- 28448326
TI  - Design of an online medication safety module for clinicians.
AB  - BACKGROUND: In Australia, there are very few online courses addressing medication
      safety issues. Educating clinicians about medication safety is paramount given
      the increased responsibility of clinicians in advanced practice roles including
      nurses at several key points throughout the medication process that encompass
      prescribing, dispensing, administering and monitoring medications. METHOD: The
      model used for the course design is based on adult teaching principles. The
      modules incorporate several knowledge-based presentations along with interactive
      activities. An integrative pedagogical approach is used in designing the modules
      in the online course. RESULTS: The online education modules target clinicians who
      work in the community setting. Although the modules are intended to reinforce the
      principles of medication safety principles identified in the literature, there is
      a focus on professional responsibility and understanding the laws governing
      medication disposals and handling. The course used an integrative approach
      suitable for pharmacy programs. CONCLUSION: The design and development of a
      medication safety online course was described by using the Australian Commission
      on Safety and Quality in Health Care and the 2011 Curriculum developed by the
      Royal Australian College of General Practitioners frameworks. The course has
      gained accreditation by the Australian Royal College of General Practice as part
      of its continuing education development programs.

PMID- 28448327
TI  - Community osteoporosis screening services for the prevention of osteoporotic
      fractures in population health: a literature review.
AB  - AIM: To determine the implications of the reviewed literature in population
      health improvement. METHOD: A review of the literature was conducted with the
      search of four databases: PubMed, PsycINFO, ERIC, and Google Scholar. Search
      terms entered into these databases were 'osteoporosis community'. After a
      thorough review of all search results, 11 studies were found to be community
      osteoporosis screening services, and descriptions of each study's participants
      and location, details and descriptions of each study's community osteoporosis
      screening service, and effectiveness on outcome measure(s) for each study's
      objective were reviewed and examined to determine their implications on
      population health. RESULTS: Nine of the 11 studies on community osteoporosis
      screening services were conducted at community pharmacy settings, and all studies
      included participants that were all or mostly older women, with only three
      studies that included men as participants. In addition to osteoporosis screening,
      all studies included osteoporosis education and/or counseling with the exception
      of one study. Various outcome measures were assessed in these studies, and with
      the exception of osteoporosis treatment adherence, weight-bearing exercise and
      osteoporosis-specified quality of life, community osteoporosis screening services
      showed positive outcomes in increasing osteoporosis awareness, osteoporosis
      knowledge, osteoporosis risk identification, calcium intake, service
      satisfaction, primary care physician perspective, and financial sustainability.
      In particular, community osteoporosis screening services are helpful in
      identifying those with osteoporosis or are at moderate risk to high risk, and
      they are effective in increasing outcomes that help prevent osteoporotic
      fractures, such as osteoporosis medication prescription and calcium intake.
      Furthermore, participants feel satisfied in partaking in community osteoporosis
      screening services, primary care physicians do believe that they are useful, and
      they are financially stable as they earn profit net gains. CONCLUSION: Community
      osteoporosis screening services provide a cost-effective approach towards
      preventing osteoporotic fractures for population health, particularly in
      identifying osteoporosis or high risk of the disease in populations. This review
      determined preventive measures for osteoporotic fractures, such as increased
      calcium intake and osteoporosis medication prescriptions, resulting in decreased
      osteoporotic fractures and increased population health improvement.

PMID- 28448328
TI  - Hospice or community network? Choices in end-of-life care in Jamaica.
AB  - AIM: Now considered a subspecialty of medicine and nursing, palliative care is a
      critical aspect of healthcare at the end of life. National and international
      healthcare agencies typically attribute its slow or haphazard growth in
      developing countries to various resource constraints. However, this study
      provides evidence of the substantial and widening gap between policy advocacy and
      patient choices in end-of-life care. It does so by establishing the incentives
      and risks that underlie decision-making by patients and providers against the
      relative scarcity of palliative care and hospices in these countries. METHODS:
      Jamaica offers an illustrative case. It shares the socioeconomic conditions and
      isolated provision of hospice and palliative care that remain prevalent in many
      developing countries. Empirical information was collected from all Jamaican
      hospices, along with agency and media reports, for comparative institutional
      analysis. RESULTS: Financial and infrastructural challenges hamper hospice
      expansion and integration into formal healthcare systems in developing countries.
      Yet, other equally vital considerations are too often neglected. These include
      the high transaction costs of decision-making, which account for limited hospice
      accessibility, affordability, and efficiency, particularly to underserved
      populations. Risk and payoff calculations by patients and their families as well
      as hospices and their providers lead to two strategic options in maximizing
      hospice value and/or minimizing transaction costs in end-of-life care.
      CONCLUSION: Policy formulation and advocacy for hospice and palliative care
      should match aggregate demand. The socio-cultural milieu of care is critical and
      should be equally considered. Otherwise, providing and expanding free or
      subsidized palliative care at the end-of-life stage can become cost-inefficient
      relative to robust family and grassroots community networks.

PMID- 28448329
TI  - Effect of educational program on self-care behaviors and health outcome among
      patients with heart failure: an experimental study.
AB  - OBJECTIVES: To implement an educational program for patients with heart failure
      and to assess its effectiveness on self-care behaviors and health outcomes
      (frequency of hospitalizations, emergency department visits, and deaths).
      METHODS: A comparative-experimental design was used. A total of 144 participants
      were randomized into the intervention group (who received individualized
      education session, self-care manual, and weekly phone calls) and the control
      group (who received usual care). RESULTS: After 3 months of follow-up, there was
      a significant difference in the self-care maintenance (P < 0.001), self-care
      management (P < 0.001), and the frequency of emergency department visits between
      the two groups (P = 0.028). CONCLUSION: The promising effect of the educational
      program on patients' health outcomes suggests that incorporating such a program
      into the standard healthcare is important. PRACTICE IMPLICATIONS: The findings of
      this study demonstrate that individualized heart failure education, which is
      supported by follow-up phone calls and self-care manual, is an effective approach
      to improve patients' adherence to self-care behaviors.

PMID- 28448330
TI  - Broadening our Perspectives: Health of Women and Children Globally.

PMID- 28448331
TI  - A Nurse-Directed Model for Nitrous Oxide Use During Labor.
AB  - BACKGROUND: Nitrous oxide has a long history of use and has been well documented
      in the literature as a safe, effective, and inexpensive option for pain
      management in labor in other countries, but it is underused in the United States.
      LOCAL PROBLEM: Pain relief options for laboring women in rural community
      hospitals with a small perinatal service are limited due to lack of availability
      of in-house anesthesia coverage. METHOD: This quality improvement project
      involved development and implementation of a nurse-driven, self-administered,
      demand-flow nitrous oxide program as an option for pain relief for laboring women
      in a rural community hospital. INTERVENTION: Women's Services registered nurses
      developed the project using an interdisciplinary team approach based on an
      extensive literature review and consultation with experts across the country. The
      hospital is part of a large healthcare system; approval was sought and obtained
      by the system as part of the project. Cost analysis and patient satisfaction data
      were evaluated. Outcomes were monitored. RESULTS: Approximately one half of the
      patients who have given birth at the hospital since initiation of the project
      have used nitrous oxide during labor. The majority of women who participated in a
      survey after birth found it helpful during mild-to-moderate labor pain. No
      adverse effects have noted in either the mother or the baby following nitrous
      oxide use. CLINICAL IMPLICATIONS: Initiation and management of nitrous oxide by
      registered nurses is a safe and cost-effective option for labor pain. It may be
      especially beneficial in hospitals that do not have 24/7 in-house anesthesia
      coverage.

PMID- 28448332
TI  - Sleep Quality and Quantity in Low-Income Postpartum Women.
AB  - PURPOSE: To describe and explore patterns of postpartum sleep, fatigue, and
      depressive symptoms in low-income urban women. STUDY DESIGN AND METHODS: In this
      descriptive, exploratory, nonexperimental study, participants were recruited from
      an inpatient postpartum unit. Subjective measures were completed by 132
      participants across five time points. Objective sleep/wake patterns were measured
      by 72-hour wrist actigraphy at 4 and 8 weeks. Mean sample age was 25 years, high
      school educated with 3.1 children. Over half the sample reported an annual income
      less than 50% of the federal poverty level. RESULTS: Objectively, total nighttime
      sleep was 5.5 hours (week 4) and 5.4 hours (week 8). Subjectively, 85% met
      criteria for "poor sleep quality" at week 4, and nearly half were persistently
      and severely fatigued through 8 weeks postpartum. CLINICAL IMPLICATIONS: The
      majority (65%) of women in this study met the definition of "short sleep
      duration," defined as sleeping <= 6 hours per night. Adverse effects of this
      short sleep on physical and mental health as well as safety and functioning,
      especially within the context of poverty, may be profound. There is an urgent
      need for further research on sleep in low-income underrepresented women to
      identify interventions that can improve sleep and fatigue as well as discern the
      implications of sleep deprivation on the safety and physical and mental health of
      this population.

PMID- 28448333
TI  - Challenges to Breastfeeding Initiation and Duration for Teen Mothers.
AB  - PURPOSE: The purpose of this study was to evaluate breastfeeding practices of
      teen mothers in a pre- and postnatal education and support program. STUDY DESIGN
      AND METHODS: We studied breastfeeding practices of primarily Hispanic and non
      Hispanic White teen mothers who participated in the Teen Outreach Pregnancy
      Services (TOPS) program, which promoted breastfeeding through prenatal
      programming and postpartum support. Analyses identified the most common reasons
      participants had not breastfed and, for those who initiated breastfeeding, the
      most common reasons they stopped. RESULTS: Participants (g = 314) reported on
      whether and for how long they breastfed. Nearly all participants reported
      initiating breastfeeding but few breastfed to 6 months. For the most part,
      reasons they reported stopping breastfeeding paralleled those previously reported
      for adult mothers across the first several months of motherhood. CLINICAL
      IMPLICATIONS: We found that teen mothers can initiate breastfeeding at high
      rates. Results highlight areas in which teen mothers' knowledge and skills can be
      supported to promote breastfeeding duration, including pain management and better
      recognizing infant cues. Our findings expand limited previous research
      investigating reasons that teen mothers who initiate breastfeeding stop before 6
      months.

PMID- 28448334
TI  - Screening for Tobacco and Nicotine Use in Pregnancy.

PMID- 28448335
TI  - Cry It Out: What Is It and Is It Appropriate?

PMID- 28448336
TI  - When Healthy Eating is Carried to the Extreme.

PMID- 28448337
TI  - Sustainable Development and the Literacy of Women and Girls.

PMID- 28448340
TI  - Global Health of Babies and Children.

PMID- 28448339
TI  - Disruptive Behavior in the Clinical Setting: Implications for Patient Safety.

PMID- 28448341
TI  - A Nurse-Directed Model for Nitrous Oxide Use During Labor.

PMID- 28448342
TI  - The Essence of Nursing Care.
AB  - Frontline nurses are central to ensuring the patient experience is positive and
      dignified.

PMID- 28448343
TI  - Health Care and the New Administration.

PMID- 28448344
TI  - Health Care and the New Administration.

PMID- 28448345
TI  - Adolescent Access to Reproductive Health Care.

PMID- 28448346
TI  - In Defense of Routine Inpatient Pain Assessment.
AB  - Getting rid of the fifth vital sign won't solve the opioid abuse crisis.

PMID- 28448347
TI  - Should Adults Experiencing In-Hospital Cardiac Arrest Be Intubated?
AB  - A new study challenges conventional wisdom.

PMID- 28448348
TI  - Analysis of Cancer Deaths at the County Level Pinpoints Hot Spots for Action.
AB  - Such localized information can help improve resource allocation.

PMID- 28448349
TI  - Do Health Food Store Staff Steer Teen Boys to Muscle-Enhancing Supplements?
AB  - No law prevents their sale to minors.

PMID- 28448352
TI  - Laundry Detergent Pods Linked to Increased Eye Injuries in Children.
AB  - Pods are responsible for over a quarter of toddlers' chemical ocular burns.

PMID- 28448354
TI  - New Clinical Guideline for Low Back Pain Says Try Nondrug Therapies First.
AB  - Most such pain resolves on its own.

PMID- 28448358
TI  - Can Health Care Professionals Do Anything About Gun Violence?
AB  - Experts say yes, but providers must speak up-and take action.

PMID- 28448359
TI  - Rare Allergic Reaction to Topical Chlorhexidine Gluconate.

PMID- 28448360
TI  - FDA Warnings Nurses can Include in Patient Education.

PMID- 28448364
TI  - Deep Tissue Pressure Injury: A Clinical Review.
AB  - : A deep tissue pressure injury (DTPI) is a serious type of pressure injury that
      begins in the muscle closest to the bone and may not be visible in its early
      stages. Its hallmark is rapid deterioration despite the use of appropriate
      preventive interventions. In 2007, the National Pressure Ulcer Advisory Panel
      added suspected deep tissue injuries to the traditional classification system,
      and by 2010 DTPIs had accounted for about 9% of all pressure injuries and were
      for the first time more prevalent than stage 3 or 4 pressure injuries. On
      average, patients who develop these injuries are older and have a lower body mass
      index than patients who develop other pressure injuries. Most commonly, DTPIs
      appear on the skin over the coccyx or sacrum, the buttocks, and the heels. This
      article discusses the pathophysiology; risk factors; and assessment, prevention,
      and treatment of DTPIs, using a composite case to illustrate the progression of
      this serious type of pressure injury.

PMID- 28448365
TI  - Discharge Planning and Teaching.
AB  - This article is the fifth in a series, Supporting Family Caregivers: No Longer
      Home Alone, published in collaboration with the AARP Public Policy Institute.
      Results of focus groups, conducted as part of the AARP Public Policy Institute's
      No Longer Home Alone video project, supported evidence that family caregivers
      aren't being given the information they need to manage the complex care regimens
      of their family members. This series of articles and accompanying videos aims to
      help nurses provide caregivers with the tools they need to manage their family
      member's medications. Each article explains the principles nurses should consider
      and reinforce with caregivers and is accompanied by a video for the caregiver to
      watch. The fifth video can be accessed at http://links.lww.com/AJN/A79.

PMID- 28448366
TI  - Project TENDR.
AB  - : Chemicals are ubiquitous in the food we eat, the water we drink, the air we
      breathe, and the products we use at work and in our personal lives. Toxic
      chemicals increase the risk of cognitive, behavioral, and neurodevelopmental
      disorders throughout the life span. The Toxic Substances Control Act of 1976 was
      intended to allow for the collection of data on and regulation of these chemicals
      but has been criticized for its significant limitations in protecting the
      public's health. In recognition of the scientific evidence demonstrating the
      connection between toxic environmental chemicals and neurodevelopmental
      disorders, Project TENDR (Targeting Environmental Neuro-Developmental Risks)-a
      collaborative initiative of scientists, health professionals, and children's
      health advocates-produced a call to action last July with the aim of reducing
      exposure to chemicals and pollutants that contribute to the development of these
      disorders.

PMID- 28448367
TI  - What a Nurse Really Wants.
AB  - Updated several times a week with posts by a wide variety of authors, AJN's blog
      Off the Charts allows us to provide more timely-and often more personal
      perspectives on professional, policy, and clinical issues. Best of the Blog will
      be a regular column to draw the attention of AJN readers to posts we think
      deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com.

PMID- 28448368
TI  - Managing Chemotherapy-Induced Anemia with Erythropoiesis-Stimulating Agents Plus
      Iron.
AB  - Editor's note: This is a summary of a nursing care-related systematic review from
      the Cochrane Library.

PMID- 28448369
TI  - What Types of Articles to Write.
AB  - : This is the third in a series of articles to help nurses share their knowledge,
      skills, and insight through writing for publication. Nurses have something
      important to contribute no matter what their nursing role. This series will help
      nurses develop good writing habits and sharpen their writing skills. It will take
      nurses step by step through the publication process, highlighting what gets
      published and why, how to submit articles and work with editors, and common
      pitfalls to avoid. For the previous articles in this series, see
      http://bit.ly/2lhnYKJ.

PMID- 28448370
TI  - The Nurse Who Saw Me.
AB  - A mother's long night at her sick newborn's side. What can possibly ease the
      strain?

PMID- 28448371
TI  - Research Societies and the Advancement of Nursing Science.

PMID- 28448372
TI  - Validity of the Montreal Cognitive Assessment Screener in Adolescents and Young
      Adults With and Without Congenital Heart Disease.
AB  - BACKGROUND: Cognitive deficits are common, long-term sequelae in children and
      adolescents with congenital heart disease (CHD) who have undergone surgical
      palliation. However, there is a lack of a validated brief cognitive screening
      tool appropriate for the outpatient setting for adolescents with CHD. One
      candidate instrument is the Montreal Cognitive Assessment (MoCA) questionnaire.
      OBJECTIVE: The purpose of the research was to validate scores from the MoCA
      against the General Memory Index (GMI) of the Wide Range Assessment of Memory and
      Learning, 2nd Edition (WRAML2), a widely accepted measure of cognition/memory, in
      adolescents and young adults with CHD. METHODS: We administered the MoCA and the
      WRAML2 to 156 adolescents and young adults ages 14-21 (80 youth with CHD and 76
      healthy controls who were gender and age matched). Spearman's rank order
      correlations were used to assess concurrent validity. To assess construct
      validity, the Mann-Whitney U test was used to compare differences in scores in
      youth with CHD and the healthy control group. Receiver operating characteristic
      curves were created and area under the curve, sensitivity, specificity, positive
      predictive value, and negative predictive value were also calculated. RESULTS:
      The MoCA median scores in the CHD versus healthy controls were (23, range 15-29
      vs. 28, range 22-30; p < .001), respectively. With the screening cutoff scores at
      <26 points for the MoCA and 85 for GMI (<1 SD, M = 100, SD = 15), the CHD versus
      healthy control groups showed sensitivity of .96 and specificity of .67 versus
      sensitivity of .75 and specificity of .90, respectively, in the detection of
      cognitive deficits. A cutoff score of 26 on the MoCA was optimal in the CHD
      group; a cutoff of 25 had similar properties except for a lower negative
      predictive value. The area under the receiver operating characteristic curve (95%
      CI) for the MoCA was 0.84 (95% CI [0.75, 0.93], p < .001) and 0.84 (95% CI [0.62,
      1.00], p = .02) for the CHD and controls, respectively. DISCUSSION: Scores on the
      MoCA were valid for screening to detect cognitive deficits in adolescents and
      young adults aged 14-21 with CHD when a cutoff score of 26 is used to
      differentiate youth with and without significant cognitive impairment. Future
      studies are needed in other adolescent disease groups with known cognitive
      deficits and healthy populations to explore the generalizability of validity of
      MoCA scores in adolescents and young adults.

PMID- 28448373
TI  - Effects of Parental Stress, Optimism, and Health-Promoting Behaviors on the
      Quality of Life of Primiparous and Multiparous Mothers.
AB  - BACKGROUND: Parental stress, optimism, and health-promoting behaviors (HPBs) are
      important predictors of the quality of life (QoL) of mothers. However, it is
      unclear how strongly these predictors affect the QoL of mothers. It is also
      unclear if the impact of these predictors on QoL differs between primiparous and
      multiparous mothers. In this study, we defined primiparous as "bearing young for
      the first time" and multiparous as "having experienced one or more previous
      childbirths." OBJECTIVES: The first objective of this study was to examine the
      relative effect of parental stress, optimism, and HPBs on the QoL of mothers. The
      second objective was to investigate if the effect of these predictors differed
      between primiparous and multiparous mothers. METHODS: One hundred ninety-four
      Australian mothers (n = 87, 44.8% primiparous mothers) participated in an online
      survey that included the Parental Stress Scale, the Health-Promoting Lifestyle
      Profile II, the Revised Life Orientation Test, and the Quality of Life Enjoyment
      and Satisfaction Questionnaire. RESULTS: All predictors (parental stress,
      optimism, and HPBs) significantly affected the QoL of mothers; higher levels of
      optimism, greater use of HPBs, and lower parental stress were associated with
      higher levels of QoL for all mothers. Parity did not affect the relationships.
      DISCUSSION: This study sheds light on the nature and unique effect of parental
      stress, optimism, and HPBs on the QoL of mothers.

PMID- 28448374
TI  - Characteristics and Correlates of Caregivers' Perceptions of Their Family
      Members' Memory Loss.
AB  - BACKGROUND: Understanding caregiver's perceptions of their family member's memory
      loss is a necessary step in planning nursing interventions to detect and address
      caregiver burden. OBJECTIVE: The purpose of this study was to characterize
      caregivers' perceptions of their family members' memory loss and identify
      potential correlates within Leventhal's common sense model (CSM). METHODS: This
      secondary analysis used baseline data from a larger randomized controlled trial.
      Patients with memory loss and their caregivers (N = 83 dyads) from the community
      were included. The adapted Brief Illness Perception Questionnaire (BIPQ) assessed
      caregivers' illness perceptions. Eight additional instruments measured correlates
      within the CSM. Responses were described; multiple linear regression was used to
      predict BIPQ dimension scores, and logistic regression was used to predict
      dichotomized BIPQ scores. RESULTS: Most caregivers were female, White, and
      spouses of the patients; they reported a range of perceptions on the nine BIPQ
      dimensions. Patients' cognitive function consistently emerged as a significant
      correlate of caregivers' illness perceptions, explaining the most variance in
      caregivers' perceived consequences, identity, and treatment control (p < .01).
      Caregivers' reactions to patients' behavioral symptoms and caregivers' trait
      anxiety were associated with perceived illness coherence (p < .01). Caregivers
      with higher severity of daily hassles and White caregivers perceived that their
      family members' memory loss would last longer (p < .001). DISCUSSION: Caregivers'
      perceptions of family members' memory loss varied; distinct dimensions of
      caregivers' illness perception were associated with a range of clinical and
      psychosocial factors. This exploratory study demonstrates the complexity of
      applying the CSM to caregivers of persons with memory loss.

PMID- 28448377
TI  - Editorial.

PMID- 28448375
TI  - PROMIS Sleep Disturbance and Sleep-Related Impairment in Adolescents: Examining
      Psychometrics Using Self-Report and Actigraphy.
AB  - BACKGROUND: The National Institutes of Health Patient-Reported Outcomes
      Measurement Information System (PROMIS) has self-reported health measures
      available for both pediatric and adult populations, but no pediatric measures are
      available currently in the sleep domains. OBJECTIVE: The purpose of this
      observational study was to perform preliminary validation studies on age
      appropriate, self-reported sleep measures in healthy adolescents. METHODS: This
      study examined 25 healthy adolescents' self-reported daytime sleepiness, sleep
      disturbance, sleep-related impairment, and sleep patterns. Healthy adolescents
      completed a physical exam at the National Institutes of Health Clinical Center
      (Bethesda, MD), had no chronic medical conditions, and were not taking any
      chronic medications. The Cleveland Adolescent Sleepiness Questionnaire (CASQ),
      PROMIS Sleep Disturbance (v. 1.0; 8a), and PROMIS Sleep-Related Impairment (v.
      1.0; 8b) questionnaires were completed, and sleep patterns were assessed using
      actigraphy. RESULTS: Total scores on the three sleep questionnaires were
      correlated (all Spearman's r > .70, p < .001). Total sleep time determined by
      actigraphy was negatively correlated with the CASQ (p = .01), PROMIS Sleep
      Disturbance (p = .02), and PROMIS Sleep-Related Impairment (p = .02). DISCUSSION:
      The field of pediatric sleep is rapidly expanding, and researchers and clinicians
      will benefit from well-designed, psychometrically sound sleep questionnaires.
      Findings suggest the potential research and clinical utility of adult versions of
      PROMIS sleep measures in adolescents. Future studies should include larger, more
      diverse samples and explore additional psychometric properties of PROMIS sleep
      measures to provide age-appropriate, validated, and reliable measures of sleep in
      adolescents.

PMID- 28448378
TI  - A Mixed Method Review of Tobacco Cessation for the Cardiopulmonary Rehabilitation
      Clinician.
AB  - PURPOSE: To systematically survey the literature, describe the current tobacco
      science, and perform a mixed method review of randomized control trials of
      tobacco research in the cardiopulmonary population. METHODS: Mixed method review
      was conducted on major resource databases. Inclusion criteria were English
      language with a minimum follow-up of 6 months, published between January 1, 2007,
      and June 30, 2016; adult smokers >=18 years of age with cardiovascular and/or
      pulmonary disease; initiation of subject recruitment from hospital or community;
      tobacco cessation (TC) as the main aim of the study; biometric validation of
      smoking status; first-line TC medications; and nonpharmacological treatments.
      RESULTS: The pooling of the 10 studies through forest plot analysis revealed the
      effect of tobacco continuous abstinence rates significant at 3, 6, and 12 months
      (total OR = 3.73; 95% CI, 2.58-5.38). Also, tobacco point prevalence rates of TC
      treatments demonstrated overall effects that were significant at the different
      end points (total OR = 2.63; 95% CI, 1.90-3.64). In both cases, the higher ORs
      were found in the 3 months end point. Most successful interventions consisted of
      a combination of pharmacological and nonpharmacological therapy (predominantly
      counseling). CONCLUSIONS: The evidence continues to support the recommended first
      line TC pharmacotherapy and nonpharmacological practices published in the 2008
      national guidelines. Implications for cardiopulmonary rehabilitation clinicians
      are discussed.

PMID- 28448379
TI  - Effect of an Outpatient Pulmonary Rehabilitation Program on Exercise Tolerance
      and Asthma Control in Obese Asthma Patients.
AB  - PURPOSE: To compare the effects of an outpatient pulmonary rehabilitation (PR)
      program on exercise tolerance and asthma control in obese and nonobese patients
      with asthma. METHODS: Nonobese (body mass index [BMI] <30 kg/m) and obese (BMI >=
      30 kg/m) patients with asthma who participated in a local multidisciplinary 12
      week PR program were analyzed retrospectively. Effects of PR were assessed by
      changes in 6-minute walking distance (6MWD) and Asthma Control Questionnaire
      (ACQ). RESULTS: A total of 138 asthma patients were included: 53 (38.4%) obese
      and 85 (61.6%) nonobese. At baseline, obese patients with asthma had a lower
      level of exercise tolerance reflected by a lower 6MWD (525 m vs 621 m; P < .001).
      After PR, the 6MWD improved significantly in both groups (>=50 m in nonobese vs
      >=45 m in obese; P < .001 in both groups). The improvement in 6MWD was clinically
      relevant in 71% of the nonobese and 60% of the obese patients. These patients had
      lower 6MWD (P = .024), higher usage of long-acting beta-agonist (P = .034) and
      oral corticosteroids (P = .033). Asthma control also improved in both groups
      (DeltaACQ -0.3 in nonobese vs DeltaACQ -0.4 in obese; P = .021 and P = .019,
      respectively). Clinically relevant improvement was achieved by 46.5% of nonobese
      and 51.9% of obese patients with asthma. The improvements between the groups were
      not statistically different. CONCLUSIONS: A standardized PR program is feasible
      in obese patients with asthma and they benefit as much as nonobese patients with
      asthma. However, there are still a large number of patients who show no
      clinically significant improvement. Patients with more severe asthma seem to
      benefit the most from PR.

PMID- 28448381
TI  - Higher Surgical Morbidity for Ulcerative Colitis Patients in the Era of
      Biologics.
AB  - OBJECTIVE: To investigate differences in surgical approach and postoperative
      outcomes for patients with ulcerative colitis (UC) before and after the
      introduction of biologic therapy. BACKGROUND: Biologic use has dramatically
      increased since Food and Drug Administration approval of infliximab. Studies
      conflict as to the effect of these agents on surgical outcomes with some
      demonstrating worse surgical outcomes whereas others have found no difference.
      METHODS: We used an administrative, all-payer, all-age group database located in
      New York State. Patients were included if they had a diagnosis of UC and
      underwent surgery for their disease from 1995 to 2013. Outcomes were compared for
      the index admission, at 90-day, and 1-year follow up. RESULTS: A total of 7070
      patients were included for analysis; 54% patients underwent surgery between 1995
      and 2005 and the remaining 46% patients underwent surgery between 2005 and 2013.
      There was a significant increase in the proportion of patients who underwent at
      least 3 procedures after 2005(14% vs 9%, P < 0.01). On adjusted analysis,
      patients undergoing surgery after 2005 had higher likelihood of major events (odd
      s ratio, OR = 1.42; 95% confidence interval, CI = 1.13-1.78), procedural
      complications (OR = 1.42; 95% CI = 1.20-1.68), and nonroutine discharge (OR =
      3.17; 95% CI = 2.79-3.60) during the index admission. Similar trends for worse
      adjusted outcomes in patients initially undergoing surgery after 2005 were seen
      at 90-day and 1-year follow up. CONCLUSIONS: Since the introduction of biologic
      agents in 2005, surgery for patients with UC is more likely to require multiple
      procedures. Despite robust adjustments, patients having surgery recently have
      worse postoperative morbidity during the index hospitalization, at 90-day and 1
      year follow up. More work is necessary to improve outcomes in these higher risk
      patients that undergo surgery.

PMID- 28448382
TI  - Visual Abstracts to Disseminate Research on Social Media: A Prospective, Case
      control Crossover Study.

PMID- 28448383
TI  - The GroinPain Trial: A Randomized Controlled Trial of Injection Therapy Versus
      Neurectomy for Postherniorraphy Inguinal Neuralgia.
AB  - OBJECTIVE: This study compares tender point infiltration (TPI) and a tailored
      neurectomy as the preferred treatment for chronic inguinodynia after inguinal
      herniorraphy. BACKGROUND: Some 11% of patients develop chronic discomfort after
      open inguinal herniorraphy. Both TPI and neurectomy have been suggested as
      treatment options, but evidence is conflicting. METHODS: Patients with chronic
      neuropathic pain after primary Lichtenstein repair and >50% pain reduction after
      a diagnostic TPI were randomized for repeated TPI (combined
      Lidocaine/corticosteroids /hyaluronic acid injection) or for a neurectomy.
      Primary outcome was success (>50% pain reduction using Visual Analog Scale, VAS)
      after 6 months. Cross-over to neurectomy was offered if TPI was unsuccessful.
      RESULTS: A total of 54 patients were randomized in a single center between
      January 2006 and October 2013. Baseline VAS was similar (TPI: 55, range 10-98 vs
      neurectomy: 53, range 18-82, P = 0.86). TPI was successful in 22% (n = 6), but a
      neurectomy was successful in 71% (n = 17, P = 0.001). After unsuccessful TPI, 19
      patients crossed over to neurectomy and their median VAS score dropped from 60 to
      14 (P = 0.001). No major complications after surgery were reported. Two-thirds of
      patients on worker's compensation returned to work. CONCLUSION: A tailored
      neurectomy is 3 times more effective than tender point infiltration in chronic
      inguinodynia after anterior inguinal hernia mesh repair. A step up treatment
      stratagem starting with tender point infiltration followed by a tailored
      neurectomy is advised.

PMID- 28448384
TI  - Cytoreductive Surgery for Metastatic Gastrointestinal Stromal Tumors Treated With
      Tyrosine Kinase Inhibitors: A 2-institutional Analysis.
AB  - OBJECTIVE: To refine treatment recommendations for patients with metastatic
      gastrointestinal stromal tumors (GISTs) treated with tyrosine kinase inhibitors
      (TKIs) and surgery. BACKGROUND: Early reports suggested that patients with
      metastatic GIST responding to TKIs treated with surgery may have favorable
      outcomes. However, identification of prognostic factors was limited by small
      cohorts. METHODS: Progression-free survival (PFS) and overall survival (OS) from
      time of surgery and from start of initial TKI was determined. Multivariate
      analysis was conducted on all patients undergoing GIST metastasectomy between
      2001 and 2014 at 2 institutions. RESULTS: We performed 400 operations on 323
      patients with metastatic GIST on TKIs. Radiographic response at time of surgery
      was classified as responsive disease (RD, n = 64, 16%), stable disease (SD, n =
      100, 25%), unifocal progressive disease (UPD, n = 132, 33%), and multifocal
      progressive disease (MPD, n = 104, 26%). For patients on imatinib before surgery,
      radiographic response was predictive of PFS from time of surgery (RD 36 months,
      SD 30 months, UPD 11 months, MPD 6 months; P < 0.001) and from imatinib
      initiation (RD 71 months, SD 51 months, UPD 47 months, MPD 33 months; P < 0.001).
      Radiographic response was predictive of OS from time of surgery (RD not reached,
      SD 110 months, UPD 59 months, MPD 24 months; P < 0.001), and from imatinib
      initiation (RD not reached, SD 144 months, UPD 105 months, MPD 66 months; P =
      0.005). Radiographic response was not predictive of PFS/OS for patients on
      sunitinib. Metastatic mitotic index >=5/50 HPF, MPD, and R2 resection were
      prognostic of worse PFS/OS; primary mutation was not. CONCLUSIONS: Surgery in
      metastatic GIST patients in the absence of MPD on imatinib is associated with
      outcomes at least comparable with second-line sunitinib and may be considered in
      select patients.

PMID- 28448386
TI  - Barriers to Goal-concordant Care for Older Patients With Acute Surgical Illness:
      Communication Patterns Extrinsic to Decision Aids.
AB  - OBJECTIVE: We sought to characterize patterns of communication extrinsic to a
      decision aid that may impede goal-concordant care. BACKGROUND: Decision aids are
      designed to facilitate difficult clinical decisions by providing better treatment
      information. However, these interventions may not be sufficient to effectively
      reveal patient values and promote preference-aligned decisions for seriously ill,
      older adults. METHODS: We conducted a secondary analysis of 31 decision-making
      conversations between surgeons and frail, older inpatients with acute surgical
      problems at a single tertiary care hospital. Conversations occurred before and
      after surgeons were trained to use a decision aid. We used directed qualitative
      content analysis to characterize patterns within 3 communication elements:
      disclosure of prognosis, elicitation of patient preferences, and integration of
      preferences into a treatment recommendation. RESULTS: First, surgeons missed an
      opportunity to break bad news. By focusing on the acute surgical problem and need
      to make a treatment decision, surgeons failed to expose the life-limiting nature
      of the patient's illness. Second, surgeons asked patients to express preference
      for a specific treatment without gaining knowledge about the patient's priorities
      or exploring how patients might value specific health states or disabilities.
      Third, many surgeons struggled to integrate patients' goals and values to make a
      treatment recommendation. Instead, they presented options and noted, "It's your
      decision." CONCLUSIONS: A decision aid alone may be insufficient to facilitate a
      decision that is truly shared. Attention to elements beyond provision of
      treatment information has the potential to improve communication and promote goal
      concordant care for seriously ill older patients.

PMID- 28448385
TI  - Extended Right Thoracic Approach Compared With Limited Left Thoracic Approach for
      Patients With Middle and Lower Esophageal Squamous Cell Carcinoma: Three-year
      Survival of a Prospective, Randomized, Open-label Trial.
AB  - OBJECTIVE: To investigate whether survival is improved by using the right
      thoracic approach (extended lymphadenectomy) compared with the left thoracic
      approach (limited lymphadenectomy) for esophageal cancer. BACKGROUND: The optimal
      surgical technique for esophageal cancer remains unclear. METHODS: Between May
      2010 and July 2012, 300 patients with middle and lower thoracic esophageal
      carcinoma were randomized to receive esophagectomy through either the right or
      left thoracic approach. Of these, 286 patients with squamous cell carcinoma
      determined by postoperative pathology were included in this analysis. Disease
      free survival (DFS) and overall survival (OS) were compared between the right (n
      = 146) and left thoracic groups (n = 140). RESULTS: The median follow-up was 55.9
      months [95% confidence interval (CI): 53.1-58.6]. The 3-year DFS rates were 62%
      and 52% in the right and left thoracic arms, respectively [hazard ratio (HR)
      0.709; 95% CI, 0.506-0.995; P = 0.047, log-rank test]. The 3-year OS rates were
      74% and 60%, respectively (HR, 0.663; 95% CI, 0.457-0.961; P = 0.029). Subgroup
      analyses revealed longer DFS in the right thoracic arm (vs left thoracic arm) in
      patients with lymph node involvement (HR, 0.632; 95% CI, 0.412-0.969, P = 0.034),
      but not in patients without lymph node involvement (HR, 0.757; 95% CI, 0.434
      1.320, P = 0.325), and in patients with R1-2 resection margins (HR, 0.495; 95%
      CI, 0.290-0.848, P = 0.009), but not R0 margins (HR, 0.944; 95% CI, 0.603-1.477,
      P = 0.801). CONCLUSIONS: Compared with the left thoracic approach, the right
      thoracic approach associated with increased DFS and OS in esophageal squamous
      cell carcinoma patients, particularly in those with lymph node involvement and/or
      R1-2 resection margins.

PMID- 28448387
TI  - Volume Increases and Shared Decision-making in Joint Replacement Bundles.

PMID- 28448388
TI  - Consideration of KRAS Mutational Status May Enhance the Prognostic Impact of
      Indeterminate Extrahepatic Disease in the Lungs, as Identified by 18FDG-PET Scan,
      in Patients With Colorectal Liver Metastases.

PMID- 28448389
TI  - Long-term Results After Oncoplastic Surgery for Breast Cancer: A 10-year Follow
      up.
AB  - OBJECTIVE: The aim of this study was to evaluate the long-term oncologic outcome
      after oncoplastic surgery (OPS). BACKGROUND: OPS combines wide tumor excision
      with reduction mammoplasty techniques thus extending breast conserving surgery to
      large tumors that might else be proposed a mastectomy. Little data are available
      about the oncologic results for breast conserving surgery of these larger tumors.
      METHODS: From January 2004 until March 2016, a total of 350 oncoplastic breast
      reductions were prospectively entered into a database. Patients were included if
      their breast reshaping included a reduction mammoplasty with skin excision (Level
      2 oncoplastic techniques). RESULTS: Histologic subtypes were: invasive ductal
      carcinoma in 219 cases (62.6%), ductal carcinoma in situ (DCIS) in 88 cases
      (25.1%), and invasive lobular carcinoma in 43 (12.3%) cases. Seventy-three of the
      invasive cancers (27.9%) received neoadjuvant chemotherapy. The mean resection
      weight was 177 grams. The mean pathological tumor size was 26 mm (range 0-180 mm)
      and varied from 23 mm (4-180 mm) for invasive cancers to 32 mm (0-100 mm) for
      DCIS. Specimen margins were involved in 12.6% of the cases; 10.5% of invasive
      ductal, 14.7% of DCIS, and 20.9% of invasive lobular. The overall breast
      conservation rate was 92% and varied from 87.4% for DCIS to 93.5% for the
      invasive cancers. Thirty-one patients (8.9%) developed one or more postoperative
      complications, inducing a delay in postoperative treatments in 4.6% of patients.
      The median follow up was 55 months. The cumulative 5-year incidences for local,
      regional, and distant recurrences were 2.2%, 1.1%, and 12.4%, respectively.
      CONCLUSIONS: Oncoplastic breast reductions allow wide resections with free
      margins and can be used for large cancers as an alternative to mastectomy.

PMID- 28448390
TI  - Comparison of Postoperative Respiratory Monitoring by Acoustic and Transthoracic
      Impedance Technologies in Pediatric Patients at Risk of Respiratory Depression.
AB  - BACKGROUND: In children, postoperative respiratory rate (RR) monitoring by
      transthoracic impedance (TI), capnography, and manual counting has limitations.
      The rainbow acoustic monitor (RAM) measures continuous RR noninvasively by a
      different methodology. Our primary aim was to compare the degree of agreement and
      accuracy of RR measurements as determined by RAM and TI to that of manual
      counting. Secondary aims include tolerance and analysis of alarm events. METHODS:
      Sixty-two children (2-16 years old) were admitted after tonsillectomy or
      receiving postoperative patient/parental-controlled analgesia. RR was measured at
      regular intervals by RAM, TI, and manual count. Each TI or RAM alarm resulted in
      a clinical evaluation to categorize as a true or false alarm. To assess accuracy
      and degree of agreement of RR measured by RAM or TI compared with manual
      counting, a Bland-Altman analysis was utilized showing the average difference and
      the limits of agreement. Sensitivity and specificity of RR alarms by TI and RAM
      are presented. RESULTS: Fifty-eight posttonsillectomy children and 4
      patient/parental-controlled analgesia users aged 6.5 +/- 3.4 years and weighting
      35.3 +/- 22.7 kg (body mass index percentile 76.6 +/- 30.8) were included. The
      average monitoring time per patient was 15.9 +/- 4.8 hours. RAM was tolerated 87%
      of the total monitoring time. The manual RR count was significantly different
      from TI (P = .007) with an average difference +/- SD of 1.39 +/- 10.6 but were
      not significantly different from RAM (P = .81) with an average difference +/- SD
      of 0.17 +/- 6.8. The proportion of time when RR measurements differed by >=4
      breaths was 22% by TI and was 11% by RAM. Overall, 276 alarms were detected (mean
      alarms/patient = 4.5). The mean number of alarms per patient were 1.58 +/- 2.49
      and 2.87 +/- 4.32 for RAM and TI, respectively. The mean number of false alarms
      was 0.18 +/- 0.71 for RAM and 1.00 +/- 2.78 for TI. The RAM was found to have
      46.6% sensitivity (95% confidence interval [CI], 0.29-0.64), 95.9% specificity
      (95% CI, 0.90-1.00), 88.9% positive predictive value (95% CI, 0.73-1.00), and
      72.1% negative predictive value (95% CI, 0.61-0.84), whereas the TI monitor had
      68.5% sensitivity (95% CI, 0.53-0.84), 72.0% specificity (95% CI, 0.60-0.84),
      59.0% positive (95% CI, 0.44-0.74), and 79.5% negative predictive value (95% CI,
      0.69-0.90). CONCLUSIONS: In children at risk of postoperative respiratory
      depression, RR assessment by RAM was not different to manual counting. RAM was
      well tolerated, had a lower incidence of false alarms, and had better specificity
      and positive predictive value than TI. Rigorous evaluation of the negative
      predictive value is essential to determine the role of postoperative respiratory
      monitoring with RAM.

PMID- 28448392
TI  - A Retrospective Study to Evaluate the Effect of Concentration of Hypertonic
      Saline on Efficacy and Safety of Epidural Adhesiolysis.
AB  - BACKGROUND: Percutaneous epidural adhesiolysis (PEA) is a minimally invasive
      procedure that is performed to relieve low back and/or lower limb pain secondary
      to adhesions or scarring in the epidural space that is refractory to conservative
      treatment. The optimal concentration of hypertonic saline might be an important
      factor in the safety and efficacy of PEA. We evaluated differences in the
      efficacy and safety of 2 concentrations of hypertonic saline (5% and 10%) used in
      lumbar PEA at our institutions in a retrospective study. METHODS: Patients who
      received lumbar PEA between January 2009 and June 2014 at either of 2 large
      civilian teaching institutions in South Korea were assigned to the 5% or 10%
      groups according to the osmolality of saline. The primary outcome of this study
      was the difference in change in the 11-point numerical rating scale (NRS) scores
      of low back and leg pain from baseline to 6 months after PEA between patients in
      the 2 groups. The number of additional epidural injections, patients'
      satisfaction with PEA, and any complications that occurred within 6 months after
      PEA were reviewed. RESULTS: This study included 543 patients (5% group, 333; 10%
      group, 210). Post-PEA NRS pain scores were significantly lower compared with
      those at baseline in both groups; however, there were no significant differences
      between the 2 groups at 6 months or any time point after PEA with regard to any
      of the clinical characteristics, except infusion-related pain, which exhibited
      borderline significance for greater scores in the 10% group compared with those
      in the 5% group (P = .041). Multivariable linear regression analysis with
      adjustments for covariates, including the number of additional epidural
      injections, revealed no significant association between patient group and the
      decrease in NRS pain scores at 6 months of follow-up. Transient adverse events
      related to PEA were recorded in 3 patients (10% group, 2; 5% group, 1).
      CONCLUSIONS: In PEA, 5% hypertonic saline exhibited similar positive outcomes
      after 6 months of follow-up as 10% hypertonic saline, with less infusion-related
      pain. This result suggests that infusion of 5% hypertonic saline may be
      considered as an alternative to 10% hypertonic saline in lumbar PEA. Further
      prospective randomized studies are required to better appreciate the outcome with
      regard to the use of different concentrations of hypertonic saline for PEA.

PMID- 28448393
TI  - Deep Neuromuscular Block and Surgical Conditions During Bariatric Surgery.

PMID- 28448394
TI  - In Response.

PMID- 28448397
TI  - Prophylactic Pentazocine Reduces the Incidence of Pruritus After Cesarean
      Delivery Under Spinal Anesthesia With Opioids: A Prospective Randomized Clinical
      Trial.
AB  - BACKGROUND: The incidence of pruritus after cesarean delivery under spinal
      anesthesia with opioids is high, ranging from 50% to 100%. Pruritus is difficult
      to prevent; however, pentazocine has been shown to be an effective treatment.
      Despite this, the prophylactic effect of pentazocine on pruritus has not been
      defined. This randomized double-blind trial aimed to evaluate the effect of
      intraoperative IV pentazocine on the incidence of opioid-induced pruritus within
      the first 24 hours after administration of neuraxial opioids. METHODS: We
      obtained institutional review board approval and written informed consent from
      the 122 patients (American Society of Anesthesiologists [ASA] physical status II;
      aged 20-40 years) scheduled for elective cesarean delivery who were included in
      this study. Spinal anesthesia was performed with 10 mg of 0.5% hyperbaric
      bupivacaine, 10 MUg of fentanyl, and 100 MUg of morphine. After delivery of the
      baby and placenta, the parturient women were randomized to intravenously receive
      15 mg (1 mL) of pentazocine or 1 mL of saline. All women received postoperative
      analgesia with the epidural infusion of 0.15% levobupivacaine. The presence of
      pruritus within the first 24 hours after intrathecal administration of opioids
      was recorded, and severity of itch, numerical rating scale (NRS) for pain, and
      adverse effects were also recorded at the time of the arrival on the ward, as
      well as 3, 6, 12, and 24 hours after the intrathecal administration of opioids.
      RESULTS: A total of 119 women completed the study. IV pentazocine reduced the
      overall incidence of pruritus within the first 24 hours compared to IV saline,
      with an estimated relative risk of 69% (95% confidence interval [CI], 52%, 90%; P
      = .007). IV pentazocine also reduced the severity of pruritus. The incidence of
      nausea and vomiting was not significantly different. There were no significant
      differences in postoperative NRS scores. CONCLUSIONS: A single 15-mg dose of IV
      pentazocine after delivery can reduce both the incidence and severity of pruritus
      in women who have received subarachnoid opioids during cesarean delivery.

PMID- 28448398
TI  - Intrathecal Morphine Versus Extended-Release Epidural Morphine for Postoperative
      Pain Control in Pediatric Patients Undergoing Posterior Spinal Fusion.
AB  - BACKGROUND: Posterior spinal fusion for scoliosis is one of the most painful
      elective pediatric surgeries. Good postoperative pain control allows early
      ambulation and return of ability to tolerate oral intake. Options for analgesia
      in this patient population are suboptimal. We hypothesized that extended-release
      epidural morphine (EREM) would provide better pain control and less adverse
      effects compared to intrathecal (IT) morphine. METHODS: The primary outcome was
      total IV morphine consumption during 0-48 hours postoperatively. Secondary
      outcomes included time until first patient-controlled analgesia (PCA) demand,
      pain scores, and adverse opioid effects. After institutional review board
      approval, 71 subjects undergoing posterior spinal fusion for idiopathic scoliosis
      completed the study. The subjects were randomly allocated to 7.5 MUg/kg IT
      morphine or 150 MUg/kg EREM. The final IT morphine and EREM groups contained 37
      and 34 subjects, respectively. Postoperative pain was treated with morphine PCA,
      ketorolac, oral oxycodone, and acetaminophen. Morphine consumption, pain scores,
      nausea and vomiting, pruritus, and respiratory depression were measured every 4
      hours. Parents completed a caregiver questionnaire about their child's pain
      control regimen after the first postoperative day. RESULTS: There was no
      difference in total morphine consumption over the first 48 hours between subjects
      in the EREM and IT morphine groups: median (range) 42.2 (5.5-123.0) and 34.0 (4.5
      128.8) mg, respectively (P = .27). EREM and IT morphine groups had no difference
      in time until first PCA demand. Pain scores were no different between the groups
      from 8 to 24 hours after surgery. Compared to IT morphine, EREM subjects had
      lower pain scores from 28 to 36 hours after surgery. The reported incidence of
      pruritus was lower in the EREM subjects. CONCLUSIONS: There was no difference in
      total morphine consumption or time until first PCA demand between the EREM and IT
      morphine groups. EREM provides a longer duration of analgesia after posterior
      spinal fusion for scoliosis and may be associated with less opioid-induced
      pruritus.

PMID- 28448399
TI  - Quality Assessment of Meta-analyses Published in Leading Anesthesiology Journals
      From 2005 to 2014.
AB  - Meta-analysis, when preceded by a systematic review, is considered the "gold
      standard" in data aggregation; however, the quality of meta-analyses is often
      questionable, leading to uncertainty about the accuracy of results. In this
      study, we evaluate the quality of meta-analyses published in 5 leading
      anesthesiology journals from 2005 to 2014. A total of 220 meta-analyses published
      in Anesthesiology, Pain, British Journal of Anaesthesia, Anaesthesia, or
      Anesthesia & Analgesia were identified for inclusion. The quality of each meta
      analysis was determined using the Revised Assessment of Multiple Systematic
      Reviews (R-AMSTAR). R-AMSTAR rated 11 questions related to systematic reviews and
      meta-analyses on a scale of 1-4, with 4 representing the highest quality. Overall
      meta-analyses quality was evaluated using a Spearmen regression analysis and
      found to positively correlate with time (rs = 0.24, P < .001). Similarly, a
      temporal association was found for conflict of interest (rs = 0.51, P < .001) and
      comprised a list of included and excluded studies (rs = 0.32, P < .001). In
      conclusion, the quality of meta-analyses published in leading anesthesiology
      journals has increased over the last decade. Furthermore, assessing the
      scientific quality of included studies in meta-analyses (P = .60) and using this
      assessment to formulate conclusions and/or recommendations (P = .67) remains
      relatively low (median R-AMSTAR: 2, interquartile range [IQR]: 2-3]; median R
      AMSTAR: 2, IQR: 1-2, respectively).

PMID- 28448400
TI  - Comparison of the Performance Between Sepsis-1 and Sepsis-3 in ICUs in China: A
      Retrospective Multicenter Study.
AB  - The definition of sepsis was updated to sepsis-3 in February 2016. However, the
      performance of the previous and new definition of sepsis remains unclear in
      China. This was a retrospective multicenter study in six intensive care unit
      (ICUs) from five university-affiliated hospitals to compare the performance
      between sepsis-1 and sepsis-3 in China. From May 1, 2016 to June 1, 2016, 496
      patients were enrolled consecutively. Data were extracted from the electronic
      clinical records. We evaluated the performance of sepsis-1 and sepsis-3 by
      measuring the area under the receiver operating characteristic curves (AUROC) to
      predict 28-day mortality rates. Of 496 enrolled patients, 186 (37.5%) were
      diagnosed with sepsis according to sepsis-1, while 175 (35.3%) fulfilled the
      criteria of sepsis-3. The AUROC of systemic inflammatory response syndrome (SIRS)
      is significantly smaller than that of sequential organ failure assessment (SOFA)
      (0.55 [95% confidence interval, 0.46-0.64] vs. 0.69 (95% confidence interval,
      0.61-0.77], P = 0.008) to predict 28-day mortality rates of infected patients.
      Moreover, 5.9% infected patients (11 patients) were diagnosed as sepsis according
      to sepsis-1 but not to sepsis-3. The APACHE II, SOFA scores, and mortality rate
      of the 11 patients were significantly lower than of patients whose sepsis was
      defined by both the previous and new criteria (8.6+/-3.5 vs. 16.3+/-6.2, P =  <
      0.001; 1 (0-1) vs. 6 (4-8), P = <0.001; 0.0 vs. 33.1%, P = 0.019). In addition,
      the APACHE II, length of stay in ICU, and 28-day mortality rate of septic
      patients rose gradually corresponding with the raise in SOFA score (but not the
      SIRS score). Sepsis-3 performed better than sepsis-1 in the study samples in ICUs
      in China.

PMID- 28448401
TI  - Clinical Significance of Incidentally Detected Torus Tubarius Calcification.
AB  - OBJECTIVES: Calcification of the torus tubarius has been rarely reported in the
      literature. Histopathologic studies have previously described cases of Eustachian
      tube calcification and cite an association with increasing patient age. The
      purpose of this study was to examine the prevalence of torus tubarius
      calcification and potential clinical significance on an unrestricted patient
      population using thin-section computed tomography (CT), which has not been
      previously reported. METHODS: After the institutional review board approval, 1571
      consecutive patients who underwent noncontrast head CT between January 2011 and
      July 2011 were retrospectively reviewed for torus tubarius calcification. Images
      were acquired at 1.25-mm slice thickness using a 64-detector row CT. Medical
      records were reviewed for chronic medical conditions including chronic kidney
      disease, alcoholism, autoimmune conditions, endocrine disorders, elevated
      alkaline phosphatase levels, history of otitis media, purified protein derivative
      positivity, history of head and neck surgery and radiation, and human
      immunodeficiency virus infection. Motion-limited studies and patients with
      limited clinical data were excluded. Statistical analyses were performed using
      the independent sample t test and Fisher exact test. RESULTS: Ten (0.6%) of 1571
      patients had torus tubarius calcification, of which 7 (70%) were unilateral, and
      3 (30%) were bilateral calcification. There was no significant association
      between torus tubarius calcification and common medical disorders including
      endocrine disorders, human immunodeficiency virus, chronic kidney disease,
      alcoholism, purified protein derivative positivity, history of head and neck
      surgery or radiation, and autoimmune diseases. CONCLUSIONS: Based on the largest
      series to date on an unrestricted population using thin-section CT imaging,
      calcification of the torus tubarius is a rare entity with an overall prevalence
      of 0.6%. Although the clinical significance remains uncertain, there is no
      significant association between torus tubarius calcification and common medical
      conditions.

PMID- 28448402
TI  - Left Atrium Measurements via Computed Tomography Pulmonary Angiogram as a
      Predictor of Diastolic Dysfunction.
AB  - PURPOSE: Left atrium (LA) enlargement on echocardiography may be an indicator of
      diastolic dysfunction (DD). It is not well known if computed tomography pulmonary
      angiography (CTPA) can detect DD. METHODS: A total of 127 patients who underwent
      both CTPA and echo within 48 hours were analyzed retrospectively. Left atrium
      diameters from CTPA were correlated with echo and evaluated against degrees of
      DD. Computed tomography pulmonary angiography pulmonary artery (PA)/aorta ratio
      was analyzed as a tool to detect pulmonary hypertension. RESULTS: There were 42%
      of patients who had DD. There was a strong correlation between LA size on CTPA
      and echo (r = 0.78). An LA greater than 4.0 cm gave a sensitivity of 68.1% and
      specificity of 73.9% for DD detection. A PA/aorta cutoff greater than 0.84
      yielded a sensitivity of 84% and specificity of 33% for pulmonary hypertension.
      CONCLUSIONS: Computed tomography pulmonary angiography measurements of LA and
      PA/aorta ratio correlate strongly with equivalent findings on echo. We suggest
      that LA and PA/aorta measurements be included on chest CTPA reports.

PMID- 28448403
TI  - Usefulness of a Low Tube Voltage: Knowledge-Based Iterative Model Reconstruction
      Algorithm for Computed Tomography Venography.
AB  - OBJECTIVES: The objective of this study was to evaluate the use of 80-kVp scans
      with knowledge-based iterative model reconstruction (IMR) for computed tomography
      venography (CTV). METHODS: This prospective study received institutional review
      board approval; a previous informed consent was obtained from all participants.
      We enrolled 30 patients with suspected deep venous thrombosis or pulmonary
      embolism who were to undergo 80-kVp CTV studies. The images were reconstructed
      with filtered back projection (FBP), hybrid iterative reconstruction (HIR), and
      IMR. The venous attenuation, image noise, and contrast-to-noise ratio at the
      iliac, femoral, and popliteal veins were compared on FBP, HIR, and IMR images. We
      performed qualitative image analysis (image noise, image contrast, image
      sharpness, streak artifacts, and overall image quality) of the 3 reconstruction
      methods and measured their reconstruction times. RESULTS: There was no
      significant difference in venous attenuation among the 3 reconstruction methods
      (P > 0.05). On IMR images, the image noise was lowest at all 3 venous locations,
      and the contrast-to-noise ratio was highest. Qualitative evaluation scores were
      also highest for IMR images. The reconstruction time for FBP, HIR, and IMR
      imaging was 25.4 +/- 1.9 seconds, 43.3 +/- 3.3 seconds, and 78.7 +/- 6.0 seconds,
      respectively. CONCLUSIONS: At clinically acceptable reconstruction times, 80-kVp
      CTV using the IMR technique yielded better qualitative and quantitative image
      quality than HIR and FBP.

PMID- 28448404
TI  - Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Ocular Melanoma as a Tool
      to Predict Metastatic Potential.
AB  - PURPOSE: This study explores the capability of dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) to differentiate tumor characteristics of metastatic
      and nonmetastatic choroidal melanoma as a potential tool for patient management.
      MATERIALS AND METHODS: A total of 13 patients (69 +/- 9 years) with choroidal
      melanoma were imaged using DCE-MRI on a 3-T MRI system with a 16-channel head
      coil. The Tofts 2-compartment model was chosen for quantification, and parameters
      K (the transfer constant from the blood plasma to the extracellular space) and
      Kep (the transfer constant from the extracellular space to the blood plasma) were
      calculated and compared. Metastasis was excluded by subsequent clinical work-up
      or confirmed by histology after targeted biopsy. RESULTS: Six patients were
      diagnosed with metastatic melanoma and 7 without. All orbital tumors were at
      least larger than 2 mm. A significant difference was identified in K between
      patients with (0.73 +/- 0.18/min) and without (1.00 +/- 0.21/min) metastatic
      melanoma (P = 0.03), whereas the difference was not significantly shown in Kep
      (2.58 +/- 1.54/min of metastatic patients vs 2.98 +/- 1.83/min of nonmetastatic
      patients, P = 0.67). CONCLUSIONS: Dynamic contrast-enhanced magnetic resonance
      imaging has the potential to differentiate orbital melanomas with metastatic and
      nonmetastatic spread. Thus, DCE-MRI has the potential to be an in vivo imaging
      technique to predict early which patients are prone to metastatic disease.

PMID- 28448405
TI  - Gastric Heterotopic Pancreas: Computed Tomography With Clinicopathologic
      Correlation.
AB  - Asymptomatic heterotopic pancreas (HP) is benign and can be monitored long term
      without further intervention. Heterotopic pancreas is sometimes surgically
      resected because it can be difficult to distinguish HP from neoplastic submucosal
      masses such as gastrointestinal stromal tumors. Although it is not very common,
      HP should be considered in the differential diagnosis when diagnosing
      extramucosal gastric masses to avoid unnecessary intervention. We review gastric
      HP with pathologic correlation to help with diagnosing HP on computed tomography.

PMID- 28448406
TI  - Two-Dimensional Spoiled Gradient-Recalled Echo Magnetic Resonance Imaging of the
      Liver Using Respiratory Navigator-Gating Techniques.
AB  - OBJECTIVE: We assessed the feasibility of T1-weighted 2-dimensional spoiled
      gradient-recalled (2D SPGR) acquisition in steady-state imaging of the liver with
      various respiratory navigator gating techniques. METHODS: A total of 12 healthy
      volunteers underwent in-phase and out-of-phase 2D SPGR imaging of the liver
      during breath-holding and free-breathing. Four techniques for respiratory
      navigation, 2 conventional navigator techniques and 2 self-navigator techniques,
      were used for free-breathing imaging. RESULTS: Good navigator waveforms were
      obtained in conventional navigation, whereas fluctuations were evident in self
      navigation. All of the 4 navigator-based methods provided better images in terms
      of background signals and visual image quality compared with images obtained with
      no respiratory control. However, differences remained in comparison with breath
      holding. Superiority of self-navigation to conventional navigation was not shown.
      CONCLUSIONS: Navigator-gating techniques improved 2D SPGR images of the liver
      acquired during free-breathing, suggesting feasibility and beneficial effects,
      although navigator-based images were still inferior to breath-hold images.

PMID- 28448407
TI  - Automated Attenuation Based Tube Potential Selection of the Lower Extremity
      Runoff: A Comparison to Fixed Kilovolt with Automated Tube Current Modulation.
AB  - PURPOSE: The aim of this study was to evaluate the impact of automated
      attenuation-based tube potential selection (ATPS) on image quality and radiation
      dose exposure parameters at a computed tomography angiography (CTA) lower
      extremity runoff. MATERIALS AND METHODS: Two hundred forty patients (156 men, 84
      women) underwent CTA examinations of the lower-extremity runoff on a second
      generation dual-source computed tomography system: 120 patients at a fixed tube
      potential of 120 kV and a tube current of 180 reference mAs, another 120 patients
      using automated ATPS. Volume computed tomography dose index (CTDIvol), dose
      length-product (DLP), body diameters, noise, signal-to-noise ratio, and
      subjective image quality were compared. RESULTS: In the ATPS group, 80 kV was
      automatically selected in 102 patients, 100 kV in 15 patients, and 120 kV in 3
      patients; 140 kV was not chosen in any of the cases. The median CTDIvol of 4.81
      mGy (2.2-10.6 mGy) and DLP of 568 mGy?cm (203-1324 mGy?cm) in the ATPS group were
      significantly lower compared with the CTDIvol of 8.1 mGy (4.4-14.4 mGy) and DLP
      of 1027.5 mGy?cm (509-1806 mGy?cm) in the fixed 120-kV group (P < 0.01). Image
      quality was comparable (P > 0.05). CONCLUSION: Automated ATPS allows for
      significant dose savings in lower-extremity runoff CTA, whereas image quality
      remains constant at a high level.

PMID- 28448408
TI  - Contained Rupture of an Abdominal Aortic Aneurysm With Extensive Vertebral Body
      and Retroperitoneal Space Destruction.
AB  - Chronic contained rupture of an abdominal aortic aneurysm with vertebral body
      erosion most commonly presents with symptoms of low back pain. Although not well
      known, vertebral body erosion or destruction may be seen in up to 25% of patients
      with sealed or contained rupture of an abdominal aortic aneurysm. This appearance
      on cross-sectional imaging may mimic a malignant or infectious process. Although
      these cases can present a diagnostic challenge, published cases of chronic
      contained rupture of an abdominal aortic aneurysm with vertebral body erosion
      demonstrate clinical and imaging similarities that, when recognized, can assist
      in diagnosis.

PMID- 28448409
TI  - Assessing Synovitis and Bone Erosion With Apparent Diffusion Coefficient in Early
      Stage of Rheumatoid Arthritis.
AB  - PURPOSE: The aim of this study was to assess the value of apparent diffusion
      coefficient (ADC) in distinguishing synovitis from joint fluid and bone erosion
      from cysts. METHODS: Twenty-eight patients with suspected rheumatoid arthritis
      underwent diffusion-weighted imaging and pre- and post-contrast-enhanced magnetic
      resonance imaging. The mean ADC values were compared between synovitis and joint
      effusion and between bone erosion and cyst. RESULTS: Mean ADC value of synovitis
      was significantly lower than that of the joint effusion (2.6 +/- 0.37 * 10 vs
      1.63 +/- 0.37 * 10 mm/s, P < 0.001; cutoff value 2.10 * 10 mm/s). Mean ADC value
      of bone erosion was significantly lower than that of the cysts (1.61 +/- 0.39 *
      10 vs 2.39 +/- 0.34 * 10 mm/s, P < 0.001; cutoff value 2.04 * 10 mm/s).
      CONCLUSION: Apparent diffusion coefficient can be used in differentiating between
      synovitis and joint effusion and between bone erosion and cysts.

PMID- 28448410
TI  - Lung Cancer in Patients With Tuberculous Fibrothorax and Empyema: Computed
      Tomography and 18F-Fluorodeoxyglucose Positron Emission Tomography Findings.
AB  - OBJECTIVE: The aim of this study was to describe the characteristics of lung
      cancers in patients with tuberculous fibrothorax or empyema. METHODS: We
      retrospectively evaluated 138 consecutive patients with a diagnosis of lung
      cancer combined with fibrothorax (n = 127) or empyema (n = 11) from January 2005
      to May 2015. All patients underwent computed tomography, and 105 underwent F
      fluorodeoxyglucose positron emission tomography. Clinical, pathologic, and
      computed tomography characteristics and maximum standardized uptake values on
      positron emission tomography of 76 cancers ipsilateral to the fibrothorax or
      empyema (group 1) were compared with those of 62 contralateral cancers (group 2).
      RESULTS: The median age at diagnosis of patients was 70 years, with a male-to
      female ratio of 8.9:1. The most common type was squamous cell carcinoma (41.3%)
      followed by adenocarcinoma (39.1%). Most were in the peripheral lung (70.3%), and
      half abutted the pleura. The median maximum standardized uptake value was 8.9.
      Tumors in group 1 were larger (median, 48.5 vs 42.8 mm, P = 0.036) and more
      advanced (T3 or T4) (P = 0.014) than those in group 2. CONCLUSIONS: Lung cancers
      ipsilateral to tuberculous fibrothorax or empyema presented larger and advanced T
      stages, and the diagnosis could be delayed. The most common type cancer was
      squamous cell carcinoma.

PMID- 28448411
TI  - Image Quality and Radiation Exposure Comparison of a Double High-Pitch
      Acquisition for Coronary Computed Tomography Angiography Versus Standard
      Retrospective Spiral Acquisition in Patients With Atrial Fibrillation.
AB  - OBJECTIVE: The aim of this study was to compare image quality and radiation dose
      of coronary computed tomography (CT) angiography performed with dual-source CT
      scanner using 2 different protocols in patients with atrial fibrillation.
      METHODS: Forty-seven patients with AF underwent 2 different acquisition
      protocols: double high-pitch (DHP) spiral acquisition and retrospective spiral
      acquisition. The image quality was ranked according to a qualitative score by 2
      experts: 1, no evident motion; 2, minimal motion not influencing coronary artery
      luminal evaluation; and 3, motion with impaired luminal evaluation. A third
      expert solved any disagreement. RESULTS: A total of 732 segments were evaluated.
      The DHP group (24 patients, 374 segments) showed more segments classified as
      score 1 than the retrospective spiral acquisition group (71.3% vs 37.4%). Image
      quality evaluation agreement was high between observers (kappa = 0.8). There was
      significantly lower radiation exposure for the DHP group (3.65 [1.29] vs 23.57
      [10.32] mSv). CONCLUSIONS: In this original direct comparison, a DHP spiral
      protocol for coronary CT angiography acquisition in patients with atrial
      fibrillation resulted in lower radiation exposure and superior image quality
      compared with conventional spiral retrospective acquisition.

PMID- 28448412
TI  - Optimizing Contrast Media Injection Protocols in Computed Tomography Angiography
      at Different Tube Voltages: Evaluation in a Circulation Phantom.
AB  - OBJECTIVES: The aim of this study was to investigate the minimum iodine delivery
      rate (IDR) and contrast media (CM) volume required for diagnostic contrast
      enhancement of 350 HU (Hounsfield units) in the ascending aorta at different kV
      settings. METHODS: Dynamic computed tomography acquisitions from 70 to 150 kV
      were performed in a circulation phantom. First, injections with IDR ranging from
      0.1 to 2.0 g I/s were tested for each kV. In the second part, the IDR was held
      constant, whereas the CM volume was reduced from 50 to 10 mL. Diagnostic aortic
      peak enhancement for each kV was compared using the Kruskal-Wallis test. P < 0.05
      was considered statistically significant. RESULTS: The mean aortic peak
      enhancement for all diagnostic IDRs was 368.7 +/- 11.1 HU. Diagnostic IDRs
      returned similar aortic peak enhancement values for all protocols (all P >=
      0.18). For the second part of the study, a diagnostic enhancement was yielded by
      using a minimum of 30 mL of CM for 110 kV, 25 mL for 100 and 90 kV, and 15 mL for
      80 and 70 kV. CONCLUSION: Our study suggests that a differentiated approach
      reducing the CM volume for tube voltages of less than 120 kV and increasing the
      IDR for higher kV settings seems to be the most effective approach.

PMID- 28448413
TI  - The Application of Iodine Quantitative Information Obtained by Dual-Source Dual
      Energy Computed Tomography on Chemoradiotherapy Effect Monitoring for Cervical
      Cancer: A Preliminary Study.
AB  - OBJECTIVE: The aim of the study is to investigate the potential contribution of
      the iodine quantitative parameters of dual-phase dual-energy computed tomography
      (DECT) scanning for chemoradiotherapy (CRT) response monitoring for cervical
      cancer. METHODS: Patients who were pathologically certified having cervical
      cancer and intended for concurrent radiotherapy and chemotherapy were
      prospectively included in our study. Contrast-enhanced DECT scanning was
      performed before CRT, which was repeated after 1 month of therapy, using a dual
      source CT scanner onset. Changes in tumor size were assessed according to RECIST
      1.0. Quantification of volume-normalized iodine uptake (mg/mL) was measured in
      dual phases and was standardized using the iodine uptake in the iliac artery. The
      decreased ratio of the standard iodine uptake was calculated and compared with
      the tumor size for the evaluation of the CRT effect. Data were analyzed using the
      statistics software SPSS version 19.0. Twenty women who performed normal pelvic
      contrast-enhanced CT scanning were randomly chosen as the control group for the
      radiation dose comparison with the dual-energy group. RESULTS: A total of 21
      patients who completed therapeutic courses and performed the contrast-enhanced CT
      scanning were subsequently evaluated. According to RECIST 1.0, 15 cases were
      classified into the regression (R, including 5 completed regression cases and 10
      partial regression cases) group. The remaining 6 cases were classified into the
      nonregression (NR, including 6 stable disease cases) group. The iodine value
      decreased ratio in the arterial phase (standardized iodine in arterial phase
      [SAI]) of the partial regression group was significantly higher than that of the
      stable disease group (P < 0.01), and there was no significant difference in the
      venous phase (P > 0.05). In a general quantitative comparison between the R group
      and the NR group before CRT, we controlled for the maximum diameter, age, iodine
      uptake in the arterial phase before CRT (pre-SAI), iodine uptake in the venous
      phase before CRT, and cell differentiated level, and we ultimately found no
      significant statistical differences except for the pre-SAI. In other words, the
      iodine value in the arterial phase of the R group before CRT was significantly
      higher than that of the NR group (P < 0.01). When the pre-SAI was 0.345, the area
      under the curve was 0.875 for therapeutic effect prediction. The mean effective
      dose was 5.63 +/- 1.68 mSv for the DECT group and 5.37 +/- 1.82 mSv for the
      control group (t = -1.137, P = 0.262), which showed no statistical difference in
      the radiation dose between the 2 scanning methods. CONCLUSIONS: The iodine
      mapping can be used to help evaluate the radiochemotherapy response effectively
      on the basis of tumor size change and can also be helpful in predicting the
      radiochemotherapy outcome for cervical cancer. The dual-phase DECT scanning did
      not increase the radiation dose and provided more valuable information, and thus,
      it was suitable for promotion in clinical application.

PMID- 28448414
TI  - Computed Tomography Features of Benign and Malignant Calcified Thyroid Nodules: A
      Single-Center Study.
AB  - OBJECTIVE: No previous studies have investigated thyroid calcification on
      computed tomography (CT) quantitatively by using Hounsfield unit (HU) values.
      This study aimed to analyze quantitative HU values of thyroid calcification on
      preoperative neck CT and to assess the characteristics of benign and malignant
      calcified thyroid nodules (CTNs). MATERIALS AND METHODS: Two hundred twenty
      patients who underwent neck CT before thyroid surgery from January 2015 to June
      2016 were included. On soft-tissue window CT images, CTNs with calcified
      components of 3 mm or larger in minimum diameter were included in this study. The
      HU values and types of CTNs were determined and analyzed. RESULTS: Of 61 CTNs in
      49 patients, there were 42 malignant nodules and 19 benign nodules. The mean
      largest diameter of the calcified component was 5.3 (2.5) mm (range, 3.1-17.1
      mm). A statistically significant difference was observed in the HU values of
      calcified portions between benign and malignant CTNs, whereas there was no
      significant difference in patient age or sex or in the size, location, or type of
      each CTN. Of the 8 CTNs with pure calcification, 3 exhibited a honeycomb pattern
      on bone window CT images, and these 3 CTNs were all diagnosed as papillary
      thyroid carcinoma on histopathological examination. CONCLUSIONS: Hounsfield unit
      values of CTNs may be helpful for differentiating malignancy from benignity.

PMID- 28448415
TI  - Investigation on Computed Tomography Features of Primary Thymic Atypical
      Carcinoid Tumors.
AB  - OBJECTIVES: The thymic atypical carcinoid tumors (aTCs) are rare. The computed
      tomography (CT) features of aTC were poorly studied, and researches under this
      topic with large samples are in a small quantity in the literature. Our aim was
      to investigate the CT features of aTC. METHODS: Eleven cases of aTC (7 men and 4
      women; mean age, 56 +/- 16 years) proved by pathology were retrospectively
      analyzed. All the patients underwent contrast-enhanced CT scans with dual phase
      (25-30 and 60-70 seconds) after contrast agent injection. Two experienced
      radiologists analyzed the imaging findings. The observing indexes of CT features
      were based on standard CT reporting terms of mediastinal masses suspicious for
      thymic malignancy, particularly on the findings of marginal cystic/necrotic
      component (MCC) sign and hypervascular sign in tumors. RESULTS: All the tumors
      were located in the anterior and/or middle mediastinum and heterogeneous
      parenchyma, with moderate to marked enhancement, and had multiple cystic/necrotic
      components. The maximum diameter of lesions ranged from 5 to 24 cm. Among the 11
      patients involved in this study, 6 patients had distant metastases, all of which
      were identified as skeletal metastases; 9 cases showed MCC sign only at the
      margin (3 cases) or at both marginal and central margins (6 cases), and 5 cases
      showed hypervascular sign. CONCLUSIONS: Our results suggested that the MCC and
      hypervascular signs should be included as characterization in addition to the
      standard features for the diagnosis of aTC.

PMID- 28448416
TI  - Analysis of a Steerable Needle for Fine Needle Aspiration and Biopsy: Efficiency
      and Radiation Dose Compared With a Conventional Straight Needle.
AB  - PURPOSE: Percutaneous computed tomography (CT)-guided needle biopsy has proven to
      be an efficacious method for sampling of many soft tissue lesions, especially
      deep-seated masses in the abdomen and pelvis. This study sought to test the
      potential for a novel steerable needle to improve localization and to reduce
      procedure duration and radiation dose compared with a conventional straight
      needle. MATERIAL AND METHODS: A fresh, raw meat sample (lean bovine flank) was
      imbedded with cylindrical radiopaque and radiolucent obstacles designed to
      simulate vessels (radiolucent objects) and bones (radiopaque objects) on CT. A
      pit-containing olive (partially radiopaque) was imbedded beyond the obstacles to
      represent the target. Two sites on the surface of the meat were selected and
      marked to determine initial needle placement. Two radiologists with different
      levels of experience proceeded to position a straight needle and the steerable
      needle from each skin site to the target using CT guidance as efficiently as
      possible, avoiding the obstacles. The total positioning time, the number of CT
      scans required for positioning, and the number of repositioning events (partial
      withdrawal followed by advancement) were tracked for the straight and steerable
      needles. RESULTS: For the straight needle, total time to reach the target was 499
      to 667 seconds (mean, 592 seconds); for the steerable needle, total time to reach
      the target was 281 to 343 seconds (mean, 309 seconds), on average, 48% lower. The
      number of CT scans needed for needle positioning averaged 6.25 for the straight
      needle and 3.5 for the steerable needle, which is 44% lower. Repositioning events
      (withdrawing and readvancing the needle) ranged from 3 to 10 for the straight
      needle (mean, 6.5) and 0 for the steerable needle. CONCLUSIONS: Using an in vitro
      model embedded with obstacles, the steerable needle performed better than a
      straight needle with regard to procedure time, needle repositioning events, and
      CT scans required for placement.

PMID- 28448417
TI  - Electrocardiography-Gated Computed Tomography of the Bronchial Arteries With
      Iterative Image Reconstruction: Clinical Evaluation and Image Quality.
AB  - BACKGROUND: The aim of this study was to apply electrocardiography (ECG)-gated
      prospective-triggered multidetector row computed tomography angiography with
      iterative model reconstruction (IMR) to optimize imaging of the bronchial
      arteries in patients with the chief complaint of hemoptysis. METHODS: This was a
      prospective observational study. Between August 2015 and June 2016, we enrolled
      31 consecutive patients with the chief complaint of hemoptysis who were scheduled
      to undergo computed tomography of the bronchial artery. Patients were randomly
      divided into 3 groups: group A, with filtered back-projection reconstruction;
      group B, with iDose reconstruction; and group C, with ECG-gated prospective
      triggered multidetector row computed tomography angiography with IMR. Image
      quality, visibility, and traceability were compared. RESULTS: Image quality,
      including signal-to-noise and contrast-to-noise ratios, visibility, and
      traceability, was best in group C. CONCLUSIONS: With the help of IMR and ECG
      synchronized prospective-triggered technology, the bronchial artery anatomy can
      be accurately depicted in patients with massive hemoptysis.

PMID- 28448418
TI  - Effects of B Value on Quantification of Rapid Diffusion Kurtosis Imaging in
      Normal and Acute Ischemic Brain Tissues.
AB  - PURPOSE: Diffusion kurtosis imaging (DKI) has been widely used to characterize
      brain tissue alterations. Diffusion-weighting factor or b value plays an
      important role in the measurement of rapid DKI and may have influential effects
      on them. The purpose of this study was to investigate the effects of b value on
      rapid DKI indices in normal and acute ischemic brain tissues. MATERIALS AND
      METHODS: This study enrolled 10 healthy subjects and 4 acute ischemic stroke
      patients. Three repeated DKI data with 6 high b values (500, 750, 1000, 1500,
      2000, 3000 s/mm) were acquired from healthy subjects, whereas nonrepeated DKI
      data with 3 high b values (1000, 2000, 3000 s/mm) were acquired from ischemic
      stroke patients. The DKI datasets were decomposed into several rapid DKI datasets
      consisting of 1 b0 and 2 high b values for comparisons. RESULTS: The results
      showed that b value significantly impacted the reproducibility and accuracy of
      DKI indices. The comparisons demonstrated that DKI with b = (0, 1000, 3000) s/mm
      exhibited more reproducible and accurate DKI indices than other DKI datasets in
      normal brain tissues, and similar results were noticed in acute ischemic brain
      tissue. CONCLUSIONS: We concluded that b value significantly impacted the
      quantification of DKI indices in both normal and acute ischemic brain tissues.

PMID- 28448419
TI  - Venous Sinus Thrombosis in Blunt Trauma: Incidence and Risk Factors.
AB  - PURPOSE: The aim of our study was to determine the incidence and risk factors of
      dural venous sinus thrombosis and epidural hemorrhage in the setting of a blunt
      trauma causing a calvarial fracture crossing a dural venous sinus. METHODS: A
      retrospective review of 472 blunt trauma patients with calvarial fracture
      crossing a dural venous sinus was performed. Two hundred ten patients who
      underwent computed tomography venography were identified and evaluated for the
      presence of dural venous sinus thrombosis and/or epidural hemorrhage. Site and
      displacement of fractures, as well as age, sex, Glasgow Coma Scale (GCS) score,
      and mechanism of injury, were considered for potential predictive value of
      thrombosis and/or epidural hemorrhage. RESULTS: We found a 23% incidence of dural
      venous sinus thrombosis in patients with a fracture traversing a dural venous
      sinus. Significant predictors of thrombosis included temporal fracture (38%
      incidence) and skull base fracture (31% incidence). Occipital fracture not
      involving the skull base was associated with a significantly decreased risk of
      thrombosis, with an incidence of 9%. Decreased GCS score and fall from height
      greater than 10 feet additionally predicted dural venous sinus thrombosis.
      Significant predictors of epidural hemorrhage included parietal fractures and
      displaced fractures, although a large percentage of nondisplaced fractures in
      other bones demonstrated epidural hemorrhage as well. CONCLUSIONS: Dural venous
      sinus thrombosis in the setting of blunt trauma with a calvarial fracture
      crossing a dural venous sinus has an incidence of 23%. Increased suspicion for
      thrombosis is warranted in patients with temporal or skull base fractures, low
      GCS score, and recent fall from great height.

PMID- 28448420
TI  - Inflow Angle of Small Paraophthalmic Aneurysms Is a Determinant of Adjacent
      Sphenoid Bone Remodeling.
AB  - OBJECTIVE: Large internal carotid artery aneurysms can cause remodeling of the
      sphenoid bone with subsequent hemorrhage into the sinus. No reports have
      demonstrated small unruptured lesions causing similar bone remodeling. The
      purpose of this study was to demonstrate our experience with small unruptured
      paraophthalmic aneurysms causing sphenoid bone remodeling, specifically when the
      optimal aneurysm inflow angle is present. METHODS: We searched our database for
      computed tomography angiography studies of small paraophthalmic aneurysms and
      assessed adjacent sphenoid bone remodeling and inflow angle. RESULTS: We found
      that aneurysms causing sphenoid remodeling represent 19.51% of all small
      paraophthalmic aneurysms at our institution and that the average inflow angle for
      these aneurysms was 94.38 degrees, significantly greater than for those not
      causing remodeling. CONCLUSIONS: Our findings add support to using computed
      tomography angiography in the follow-up of aneurysms to assess surrounding bone
      changes and to the development of a more evidence-based approach in the
      management of small paraophthalmic aneurysms, which currently may be managed
      conservatively.

PMID- 28448421
TI  - Multislice Computed Tomography Assessment of Tracheobronchial Patterns in Partial
      Anomalous Left Pulmonary Artery.
AB  - OBJECTIVE: The aim of this study was to present relationship between partial
      anomalous left pulmonary artery (PALPA) and the tracheobronchial tree and
      patterns of the tracheobronchial tree assessed by multislice computed tomography
      (MSCT). METHODS: Nine patients were assessed by MSCT. The relationships between
      the tracheobronchial tree and PALPA and different tracheobronchial patterns,
      location of tracheobronchial stenosis, severity of stenosis, and associated
      cardiac defects were evaluated. The results of MSCT for these patients were
      compared with the operative findings. RESULTS: The anatomy of PALPA was clearly
      identified by MSCT in all 9 patients. Three relationships between PALPA and the
      tracheobronchial tree were noted. In addition, 3 patterns of tracheobronchial
      tree anatomy were also demonstrated. The PALPA arose from the right pulmonary
      artery, forming a pulmonary sling (n = 2). The PALPA, which arose from the
      proximal right pulmonary artery, went below the tracheal bifurcation and passed
      anterior (n = 1) or inferior-anterior (n = 6) to the proximal left main bronchus.
      Three patterns of the tracheobronchial tree were presented with normal (n = 5),
      normal pattern with right tracheal bronchus (n = 3), and bridging bronchus (n =
      1). The rate of tracheobronchial stenosis was 56% (5/9).Five patients underwent
      operation, and at that time, the relationship between PALPA and the
      tracheobronchial tree defined on MSCT was confirmed. CONCLUSIONS: The PALPA can
      be associated with tracheobronchial anomalies and airway compression depending on
      its orientation to the airway. Noninvasive imaging modalities such as MSCT will
      be helpful for making further management decisions.

PMID- 28448422
TI  - Iterative Reconstruction Designed for Brain CT: A Correlative Study With Filtered
      Back Projection for the Diagnosis of Acute Ischemic Stroke.
AB  - OBJECTIVES: The objective of this study is to evaluate the usefulness of
      iterative model reconstruction designed for brain computed tomography (CT) (IMR
      Neuro) for the diagnosis of acute ischemic stroke. METHODS: This retrospective
      study included 20 patients with acute middle cerebral artery infarction who have
      undergone brain CT and 20 nonstroke patients (control). We reconstructed axial
      images with filtered back projection (FBP) and IMR-Neuro (slice thickness, 1 and
      5 mm). We compared the CT number of the infarcted area, the image noise,
      contrast, and the contrast to noise ratio of the infarcted and the noninfarcted
      areas between the different reconstruction methods. We compared the performance
      of 10 radiologists in the detection of parenchymal hypoattenuation between 2
      techniques using the receiver operating characteristic (ROC) techniques with the
      jackknife method. RESULTS: The image noise was significantly lower with IMR-Neuro
      [5 mm: 2.5 Hounsfield units (HU) +/- 0.5, 1 mm: 3.9 HU +/- 0.5] than with FBP (5
      mm: 4.9 HU +/- 0.5, 1 mm: 10.1 HU +/- 1.4) (P < 0.01). The contrast to noise
      ratio was significantly greater with IMR-Neuro (5 mm: 2.6 +/- 2.1, 1 mm: 1.6 +/-
      1.3) than with FBP (5 mm: 1.2 +/- 1.0; 1 mm: 0.6 +/- 0.5) (P < 0.01). The value
      of the average area under the receiver operating curve was significantly higher
      with IMR-Neuro than FBP (5 mm: 0.79 vs 0.74, P = 0.04; 1 mm: 0.76 vs 0.69, P =
      0.04). CONCLUSIONS: Compared with FBP, IMR-Neuro improves the image quality and
      the performance for the detection of parenchymal hypoattenuation with acute
      ischemic stroke.

PMID- 28448423
TI  - Dual-Energy CT: Balance Between Iodine Attenuation and Artifact Reduction for the
      Evaluation of Head and Neck Cancer.
AB  - OBJECTIVE: Dual-energy computed tomography high energy virtual monochromatic
      images (VMIs) can reduce artifact but suppress iodine attenuation in enhancing
      tumor. We investigated this trade-off to identify VMI(s) that strike the best
      balance between iodine detection and artifact reduction. METHODS: The study was
      performed using an Alderson radiation therapy phantom. Different iodine solutions
      (based on estimated tumor iodine content in situ using dual-energy computed
      tomography material decomposition) and different dental fillings were
      investigated. Spectral attenuation curves and quality index (QI: 1/SD) were
      evaluated. RESULTS: The relationship between iodine attenuation and QI depends on
      artifact severity and iodine concentration. For low to average concentration
      solutions degraded by mild to moderate artifact, the iodine attenuation and QI
      curves crossed at 95 keV. CONCLUSIONS: High energy VMIs less than 100 keV can
      achieve modest artifact reduction while preserving sufficient iodine attenuation
      and could represent a useful additional reconstruction for evaluation of head and
      neck cancer.

PMID- 28448424
TI  - Rapid Intraocular Tube Trimming for Glaucoma Drainage Implant Devices.
AB  - PURPOSE: To describe a new approach for shortening silicone tubes of glaucoma
      drainage devices (GDDs). MATERIALS AND METHODS: A retrospective intervention case
      series describing 3 patients undergoing the same treatment at a single
      institutional center RESULTS:: Three patients underwent successful ab interno
      trimming of GDD silicone tubes without complication CONCLUSIONS:: This technique
      allows for rapid and successful shortening of GDD tubes via an ab interno
      approach avoiding risks of traditional glaucoma tube trimming approaches.

PMID- 28448425
TI  - Vulnerability to Psychopathology and Dimensions of Personality in Patients With
      Fibromyalgia.
AB  - OBJECTIVE: Fibromyalgia (FM) patients may present psychopathology and some
      characteristic personality traits that may affect their adaptation to the
      disease. The aim of this paper was to study the relationship between personality
      dimensions according to the psychobiological model of Cloninger and the presence
      of psychopathology. MATERIALS AND METHODS: The study sample consisted of 42
      patients with FM and 38 pain-free controls. The assessment instruments
      administered were the Temperament and Character Inventory-Revised and the Millon
      Clinical Multiaxial Inventory. RESULTS: A higher proportion of clinical
      psychopathologic syndromes (CPS) was observed in the FM group than in the control
      group, the most prevalent being anxiety disorder and dysthymia. Patients with FM
      (with CPS or without CPS) presented higher Harm Avoidance than the control group,
      and the presence of a CPS also increased Harm Avoidance scores. FM patients with
      CPS had low Self-directedness (SD) compared with both the control group and with
      their FM peers without CPS. Purposefulness and Anticipatory worry-Pessimism
      explained 38% of the variance of dysthymia, and anticipatory worry-Pessimism
      explained 18% of the variance of anxiety disorders. CONCLUSIONS: Patients with FM
      have a high probability of anxious-depressive-type psychopathologic alterations.
      Their vulnerability to these conditions may be determined by personality traits.
      The SD character dimension may have implications for therapy, as low SD is
      associated with the presence of psychopathology and with a low capacity to cope
      with the disease.

PMID- 28448426
TI  - Orexin Receptor Antagonism in Painful Diabetic Neuropathy: A Phase 2 Trial With
      Filorexant.
AB  - OBJECTIVES: To evaluate whether orexin receptor antagonism with filorexant
      provides pain relief in patients with painful diabetic neuropathy (PDN). METHODS:
      In this double-blind, placebo-controlled, enriched-enrollment, randomized
      withdrawal proof-of-concept study, patients with PDN (aged 18 to 75 y) entered a
      2-week, single-blind active run-in period with filorexant 10 mg nightly, before
      randomization 1:1 to placebo or filorexant in a 2-week, double-blind treatment
      period. The primary efficacy endpoint was time to efficacy failure among "primary
      responders" (>=30% decrease in evening pain intensity during the run-in).
      Secondary endpoints were time to efficacy failure among "all responders" (>=20%
      decrease in evening pain intensity during the run-in) and mean change from
      baseline in evening pain intensity throughout last 3 days of the double-blind
      period. RESULTS: Of the 182 patients treated during the run-in, 170 were
      randomized in the double-blind period, including 65 primary responders and 88
      responders. There was no significant difference in proportion of patients with
      efficacy failure during the double-blind period with filorexant versus placebo
      among primary (24.3% vs. 32.1% [P=0.411]) or all (34.0% vs. 43.9% [nominal
      P=0.302]) responders or in mean change from baseline in evening pain intensity
      scores (estimated treatment difference: -0.587 [P=0.269], primary; -0.687
      [P=0.108], all). Adverse events were reported by 24.7% of patients during the run
      in. A higher proportion of patients treated with filorexant versus placebo
      reported adverse events during the double-blind period (23.9% vs. 13.4%).
      DISCUSSION: These data do not provide evidence for the efficacy of nightly
      filorexant for the treatment of PDN.

PMID- 28448427
TI  - Primary Care Sports Medicine Fellowship: AMSSM Proposed Standards of Excellence.
AB  - The American Medical Society for Sports Medicine (AMSSM) recognizes a need to
      provide direction and continually enhance the quality of sports medicine
      fellowship training programs. This document was developed to be an educational
      resource for sports medicine physicians who teach in a 1-year primary care sports
      medicine fellowship training program. It is meant to provide high standards and
      targets for fellowship training programs that choose to reassess their curriculum
      and seek to make improvements.

PMID- 28448428
TI  - Therapeutic Ultrasound in Navicular Stress Injuries in Elite Track and Field
      Athletes.
AB  - OBJECTIVE: To ascertain whether therapeutic ultrasound (TUS) can be used to
      assess the progression of conservative management in navicular stress injuries.
      DESIGN: This is a prospective, clinical case series. Level of evidence IV.
      SETTING: All participants were examined and followed up in a private Sports
      Injury Clinic. PARTICIPANTS: Ten elite track and field athletes with severe
      dorsal midfoot pain over the navicular bone participated in this study.
      INTERVENTIONS: All patients underwent both TUS and magnetic resonance imaging
      (MRI) evaluation. The painful threshold of TUS on initial evaluation was a mean
      of 0.707 +/- 149 W/cm, and MRI detected a navicular stress injury in all
      patients. The athletes received conservative treatment and underwent sequential
      TUS evaluations at 4, 8, 12 and 16 weeks. MAIN OUTCOME MEASURES: Therapeutic
      ultrasound pain threshold values were recorded, and the patients were
      additionally asked to grade local tenderness on a Visual Analogue Scale. Time to
      return to play was also recorded. RESULTS: The level of pain produced by the
      application of TUS on a navicular stress fracture seemed to correlate well with
      Visual Analogue Scale scores and the grade of fracture demonstrated on MRI. The
      initial low TUS painful mean value increased to a normal mean value of 1.97 +/-
      0.067 W/cm by 16 weeks. When clinical and TUS findings had returned to normal,
      the patients were allowed to return to sports activities, with no recurrences
      experienced during the study period. CONCLUSIONS: The production of pain
      associated with the application of TUS on a navicular stress fracture is a safe
      and reproducible method of monitoring the resolution of these fractures. We have
      used it successfully in making return-to-play decisions for elite level track and
      field athletes.

PMID- 28448429
TI  - Reply.

PMID- 28448430
TI  - Family Dog-Assisted Adapted Physical Activity: A Case Study.
AB  - Purpose: The aim of this case study was to examine the individual effects of an
      adapted physical activity, animal-assisted intervention (APA-AAI) with the family
      dog on motor skills, physical activity, and quality of life of a child with
      cerebral palsy (CP). Method: This study used an A-B-A single-subject design. The
      assessment phase (phase A) occurred pre- and post-intervention. This consisted of
      standardized assessments of motor skills, quality of life questionnaires,
      physical activity (measured using the GT3X+ accelerometer) and the human-animal
      bond. The intervention (phase B) lasted 8 weeks and consisted of adapted physical
      activities performed with the family dog once a week for 60 min in a lab setting.
      In addition, the participant had at-home daily activities to complete with the
      family dog. Results: Visual analysis was used to analyze the data. Motor skill
      performance, physical activity, quality of life and human animal interaction
      gains were observed in each case. Conclusions: These preliminary results provided
      initial evidence that the family-dog can play a role in healthy lifestyles
      through APA-AAI in children with CP.

PMID- 28448431
TI  - A Type-2 Block-Component-Decomposition Based 2D AOA Estimation Algorithm for an
      Electromagnetic Vector Sensor Array.
AB  - This paper investigates a two-dimensional angle of arrival (2D AOA) estimation
      algorithm for the electromagnetic vector sensor (EMVS) array based on Type-2
      block component decomposition (BCD) tensor modeling. Such a tensor decomposition
      method can take full advantage of the multidimensional structural information of
      electromagnetic signals to accomplish blind estimation for array parameters with
      higher resolution. However, existing tensor decomposition methods encounter many
      restrictions in applications of the EMVS array, such as the strict requirement
      for uniqueness conditions of decomposition, the inability to handle partially
      polarized signals, etc. To solve these problems, this paper investigates tensor
      modeling for partially-polarized signals of an L-shaped EMVS array. The 2D AOA
      estimation algorithm based on rank- ( L 1 , L 2 , . ) BCD is developed, and the
      uniqueness condition of decomposition is analyzed. By means of the estimated
      steering matrix, the proposed algorithm can automatically achieve angle pair
      matching. Numerical experiments demonstrate that the present algorithm has the
      advantages of both accuracy and robustness of parameter estimation. Even under
      the conditions of lower SNR, small angular separation and limited snapshots, the
      proposed algorithm still possesses better performance than subspace methods and
      the canonical polyadic decomposition (CPD) method.

PMID- 28448432
TI  - Base-Promoted Synthesis of beta-Substituted-Tryptophans via a Simple and
      Convenient Three-Component Condensation of Nickel(II) Glycinate.
AB  - A three-component reaction of nickel(II) glycinate was conducted for the
      convenient synthesis of beta-substituted-tryptophans. The reaction worked
      smoothly under mild conditions and the procedure was simple and easy to handle.

PMID- 28448433
TI  - Prevalence and Correlates of Suspected Nonalcoholic Fatty Liver Disease in
      Chinese Children.
AB  - Nonalcoholic fatty liver disease (NAFLD) has become a serious public health
      problem worldwide; however, the availability of information on the prevalence of
      NAFLD in the general pediatric population is still limited. The primary aim of
      this study was to reveal the prevalence and correlates of suspected NAFLD in
      Chinese children at the national level. Data from the China Health and Nutrition
      Surveys (CHNS) was used. Weight, height, waist circumference (WC), blood pressure
      (BP) were measured for children aged 7-18 years. Blood samples were collected and
      analyzed. Children were classified as having suspected NAFLD if common causes of
      liver disease were excluded, and serum alanine aminotransferase (ALT) values were
      above the established thresholds (>22.1 IU/L for girls and >25.8 IU/L for boys).
      A percentage of 9.03% (75 out of 831) of Chinese children was found to have
      suspected NAFLD. Overweight and obesity according to BMI percentiles, abdominal
      obesity, hyperuricemia (uric acid (UA) > 327 MUmol/L), and elevated total
      cholesterol (TC) were all detected as the correlates of childhood suspected NAFLD
      when adjusting for other factors. Our study revealed the prevalence of suspected
      NAFLD in general Chinese children at the national level for the first time. Our
      findings indicate that suspected NAFLD in children is associated with increasing
      childhood morbidities, further studies are needed to better understand the
      prevalence of childhood NAFLD and its correlates, and large-scale programs should
      be launched to screen NAFLD in the pediatric population in China.

PMID- 28448434
TI  - Static Memory Deduplication for Performance Optimization in Cloud Computing.
AB  - In a cloud computing environment, the number of virtual machines (VMs) on a
      single physical server and the number of applications running on each VM are
      continuously growing. This has led to an enormous increase in the demand of
      memory capacity and subsequent increase in the energy consumption in the cloud.
      Lack of enough memory has become a major bottleneck for scalability and
      performance of virtualization interfaces in cloud computing. To address this
      problem, memory deduplication techniques which reduce memory demand through page
      sharing are being adopted. However, such techniques suffer from overheads in
      terms of number of online comparisons required for the memory deduplication. In
      this paper, we propose a static memory deduplication (SMD) technique which can
      reduce memory capacity requirement and provide performance optimization in cloud
      computing. The main innovation of SMD is that the process of page detection is
      performed offline, thus potentially reducing the performance cost, especially in
      terms of response time. In SMD, page comparisons are restricted to the code
      segment, which has the highest shared content. Our experimental results show that
      SMD efficiently reduces memory capacity requirement and improves performance. We
      demonstrate that, compared to other approaches, the cost in terms of the response
      time is negligible.

PMID- 28448435
TI  - A Resident's Perspective of Ovarian Cancer.
AB  - Identifying, understanding, and curing disease is a lifelong endeavor for any
      medical practitioner. Equally as important is to be cognizant of the impact a
      disease has on the individual suffering from it, as well as on their family.
      Ovarian cancer is the leading cause of death from gynecologic malignancies.
      Symptoms are vague, and the disease is generally at an advanced stage at
      diagnosis. Efforts have been made to develop methods to identify ovarian cancer
      at earlier stages, thus improving overall mortality. Transvaginal ultrasound
      (TVUS), with and without laboratory tests, can be used to screen for ovarian
      cancer. For over thirty years, the University of Kentucky Markey Cancer Center
      Ovarian Cancer Screening Program has been studying the efficacy of TVUS for
      detecting early stage ovarian cancer. After 285,000+ TVUS examinations provided
      to over 45,000 women, the program has demonstrated that regular TVUS examinations
      can detect ovarian cancer at early stages, and that survival is increased in
      those women whose ovarian cancer was detected with screening and who undergo
      standard treatment. These results demonstrate the utility of TVUS as an
      efficacious method of ovarian cancer screening.

PMID- 28448436
TI  - Role of Archaeal HerA Protein in the Biology of the Bacterium Thermus
      thermophilus.
AB  - Intense gene flux between prokaryotes result in high percentage of archaeal genes
      in the genome of the thermophilic bacteria Thermus spp. Among these archaeal
      genes a homolog to the Sulfolobus spp. HerA protein appears in all of the Thermus
      spp. strains so far sequenced (HepA). The role of HepA in Thermus thermophilus
      HB27 has been analyzed using deletion mutants, and its structure resolved at low
      resolution by electron microscopy. Recombinant HepA shows DNA-dependent ATPase
      activity and its structure revealed a double ring, conically-shaped hexamer with
      an upper diameter of 150 A and a bottom module of 95 A. A central pore was
      detected in the structure that ranges from 13 A at one extreme, to 30 A at the
      other. Mutants lacking HepA show defective natural competence and DNA donation
      capability in a conjugation-like process termed "transjugation", and also high
      sensitivity to UV and dramatic sensitivity to high temperatures. These data
      support that acquisition of an ancestral archaeal HerA has been fundamental for
      the adaptation of Thermus spp. to high temperatures.

PMID- 28448437
TI  - Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/beta-Catenin
      Signaling Pathway.
AB  - The abnormal elevation of sulfiredoxin (Srx/SRXN1)-an antioxidant enzyme whose
      main function is to protect against oxidative stress-has been shown to be closely
      correlated with the progression of several types of cancer, including human
      cervical cancer. However, the molecular mechanism by which Srx promotes tumor
      progression, especially cancer metastasis in cervical cancer, has not been
      elucidated. Here, we show that Srx expression gradually increases during the
      progression of human cervical cancer and its expression level is closely
      correlated with lymph node metastasis. Our study also reveals a significant
      positive correlation between the expression of Srx and beta-catenin in cervical
      cancer tissues. Loss-of-function studies demonstrate that Srx knockdown using a
      lentiviral vector-mediated specific shRNA decreases the migration and invasion
      capacity in HeLa (human papilloma virus 18 type cervical cancer cell line) and
      SiHa SiHa (cervical squamous cancer cell line). Notably, the exact opposite
      effects were observed in gain-of-function experiments in C-33A cells.
      Mechanistically, downregulation or upregulation of Srx leads to an altered
      expression of proteins associated with the Wnt/beta-catenin signaling pathway.
      Furthermore, blockage of the Wnt/beta-catenin signaling pathway contributed to
      attenuated Srx expression and resulted in significant inhibition of cell
      migration and invasion in cervical cancer cell lines. Combined, Srx might be an
      oncoprotein in cervical cancer, playing critical roles in activating the Wnt/beta
      catenin signaling pathway; it may therefore be a therapeutic target for cervical
      cancer.

PMID- 28448438
TI  - Antiplatelet Activity of a Newly Synthesized Novel Ruthenium (II): A Potential
      Role for Akt/JNK Signaling.
AB  - In oncotherapy, ruthenium complexes are considered as potential alternatives for
      platinum compounds, and have been proved as promising anticancer drugs with high
      efficacy and lesser side effects. Platelet activation plays a major role in
      cancer metastasis and progression. Hence, this study explored the effect of a
      newly synthesized ruthenium complex, [Ru(eta6-cymene)(L)Cl]BF4(TQ5), where L = 4
      phenyl-2-pyridin-2-yl-quinazoline), on human platelet activation. TQ5 (3-5 uM)
      inhibited concentration-dependent collagen-induced platelet aggregation in washed
      human platelets. However, this compound only inhibited platelet aggregation at a
      maximum concentration of 500 and 100 uM against thrombin and 9,11-dideoxy
      11alpha, 9alpha-epoxymethanoprostaglandin (U46619)-induced stimulation,
      respectively. TQ5 inhibited collagen-induced ATP release and calcium mobilization
      ([Ca2+]i), without inducing cell cytotoxicity. In addition, neither SQ22536, an
      adenylate cyclase inhibitor, nor 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one
      (ODQ), a guanylate cyclase inhibitor, significantly reversed the TQ5-mediated
      inhibition of platelet aggregation. TQ5 inhibited the collagen-induced
      phosphorylation of protein kinase B (Akt) and c-Jun N-terminal kinase (JNK), but
      did not effectively inhibit extracellular signal-regulated kinase 1/2 (ERK1/2)
      and p38-mitogen-activated protein kinase (p38-MAPK) in human platelets.
      Additionally, TQ5 significantly prolonged the closure time in whole blood and
      increased the occlusion time of thrombotic platelet plug formation in mice. This
      study demonstrates, for the first time, that a newly synthesized ruthenium
      complex, TQ5, exhibits potent antiplatelet activity by hindering ATP release and
      [Ca2+]i, and by decreasing the activation of Akt/JNK signals. Together, these
      results suggest that TQ5 could be developed as a therapeutic agent that helps
      prevent or treat thromboembolic disorders, since it is found to be potently more
      effective than a well-established antithrombotic aspirin.

PMID- 28448439
TI  - YKL-40-Induced Inhibition of miR-590-3p Promotes Interleukin-18 Expression and
      Angiogenesis of Endothelial Progenitor Cells.
AB  - YKL-40, also known as human cartilage glycoprotein-39 or chitinase-3-like-1, is a
      pro-inflammatory protein that is highly expressed in rheumatoid arthritis (RA)
      patients. Angiogenesis is a critical step in the pathogenesis of RA, promoting
      the infiltration of inflammatory cells into joints and providing oxygen and
      nutrients to RA pannus. In this study, we examined the effects of YKL-40 in the
      production of the pro-inflammatory cytokine interleukin-18 (IL-18), and the
      stimulation of angiogenesis and accumulation of osteoblasts. We observed that YKL
      40 induces IL-18 production in osteoblasts and thereby stimulates angiogenesis of
      endothelial progenitor cells (EPCs). We found that this process occurs through
      the suppression of miR-590-3p via the focal adhesion kinase (FAK)/PI3K/Akt
      signaling pathway. YKL-40 inhibition reduced angiogenesis in in vivo models of
      angiogenesis: the chick embryo chorioallantoic membrane (CAM) and Matrigel plug
      models. We report that YKL-40 stimulates IL-18 expression in osteoblasts and
      facilitates EPC angiogenesis.

PMID- 28448440
TI  - Is Polysialylated NCAM Not Only a Regulator during Brain Development But also
      during the Formation of Other Organs?
AB  - In mammals several cell adhesion molecules are involved during the pre- and
      postnatal development of all organ systems. A very prominent member of this
      family is the neural cell adhesion molecule (NCAM). Interestingly, NCAM can be a
      target for a special form of posttranslational modification: polysialylation.
      Whereas nearly all extracellular proteins bear mono-sialic acid residues, only a
      very small group can be polysialylated. Polysialic acid is a highly negatively
      charged sugar polymer and can comprise more than 90 sialic acid residues in
      postnatal mouse brains increasing dramatically the hydrodynamic radius of their
      carriers. Thus, adhesion and communication processes on cell surfaces are
      strongly influenced allowing, e.g., the migration of neuronal progenitor cells.
      In the developing brain the essential role of polysialylated NCAM has been
      demonstrated in many studies. In comparison to the neuronal system, however,
      during the formation of other organs the impact of the polysialylated form of
      NCAM is not well characterized and the number of studies is limited so far. This
      review summarizes these observations and discusses possible roles of
      polysialylated NCAM during the development of organs other than the brain.

PMID- 28448441
TI  - Characterization of Compounds with Tumor-Cell Proliferation Inhibition Activity
      from Mushroom (Phellinus baumii) Mycelia Produced by Solid-State Fermentation.
AB  - The inhibition of tumor-cell proliferationbyan organicsolvent extract from the
      solid-state fermentation of Phellinus baumii mycelia inoculated in rice medium
      was investigated in vitro. The active compounds inhibiting tumor-cell
      proliferation were characterized. Results revealed that all (petroleum ether,
      chloroform, ethyl acetate, and butanol) fractions inhibited tumor-cell
      proliferation in a dose-dependent fashion. The ethyl acetate extract had the
      highest inhibitory effecton tumor-cell proliferation, and the butanol fraction
      had the lowest. Six compounds were isolated and purified from the ethyl acetate
      extract of P. baumii mycelia by the tandem application of silica-gel column
      chromatography (SGCC), high-speed countercurrent chromatography (HSCCC), and
      preparative HPLC. These compounds were identified by NMR and electrospray
      ionization-mass spectrometry (ESI-MS) spectroscopic methods as ergosterol (RF1),
      ergosta-7,22-dien-3beta-yl pentadecanoate (RF3), 3,4-dihydroxy benzaldehyde(RF6),
      inoscavinA (RF7), baicalein(RF10), and 24-ethylcholesta-5,22-dien-3beta-ol
      (RF13). To further clarify the activity of these compounds, the cell
      proliferation-inhibition tests of these compounds on various tumor cells were
      carried out and evaluatedin vitro. Results suggested that compounds RF6, RF7, and
      RF10 had potent inhibition effects on the proliferation of a series of tumor cell
      lines, including K562, L1210, SW620, HepG2, LNCaP, and MCF-7cells. These findings
      indicated that P. baumii mycelia produced by solid-state fermentation in rice
      canbe used to obtain active compounds with the ability to inhibittumor-cell
      proliferation.

PMID- 28448442
TI  - Rai1 Haploinsufficiency Is Associated with Social Abnormalities in Mice.
AB  - Background: Autism is characterized by difficulties in social interaction,
      communication, and repetitive behaviors; with different degrees of severity in
      each of the core areas. Haploinsufficiency and point mutations of RAI1 are
      associated with Smith-Magenis syndrome (SMS), a genetic condition that scores
      within the autism spectrum range for social responsiveness and communication, and
      is characterized by neurobehavioral abnormalities, intellectual disability,
      developmental delay, sleep disturbance, and self-injurious behaviors. Methods: To
      investigate the relationship between Rai1 and social impairment, we evaluated the
      Rai1+/- mice with a battery of tests to address social behavior in mice. Results:
      We found that the mutant mice showed diminished interest in social odors,
      abnormal submissive tendencies, and increased repetitive behaviors when compared
      to wild type littermates. Conclusions: These findings suggest that Rai1
      contributes to social behavior in mice, and prompt it as a candidate gene for the
      social behaviors observed in Smith-Magenis Syndrome patients.

PMID- 28448443
TI  - The Effect of Thermal Fluctuation on the Receptor-Mediated Adhesion of a Cell
      Membrane to an Elastic Substrate.
AB  - Mechanics of the bilayer membrane play an important role in many biological and
      bioengineering problems such as cell-substrate and cell-nanomaterial
      interactions. In this work, we study the effect of thermal fluctuation and the
      substrate elasticity on the cell membrane-substrate adhesion. We model the
      adhesion of a fluctuating membrane on an elastic substrate as a two-step reaction
      comprised of the out-of-plane membrane fluctuation and the receptor-ligand
      binding. The equilibrium closed bond ratio as a function of substrate rigidity
      was computed by developing a coupled Fourier space Brownian dynamics and Monte
      Carlo method. The simulation results show that there exists a crossover value of
      the substrate rigidity at which the closed bond ratio is maximal.

PMID- 28448445
TI  - Horizontal Directional Drilling-Length Detection Technology While Drilling Based
      on Bi-Electro-Magnetic Sensing.
AB  - The drilling length is an important parameter in the process of horizontal
      directional drilling (HDD) exploration and recovery, but there has been a lack of
      accurate, automatically obtained statistics regarding this parameter. Herein, a
      technique for real-time HDD length detection and a management system based on the
      electromagnetic detection method with a microprocessor and two magnetoresistive
      sensors employing the software LabVIEW are proposed. The basic principle is to
      detect the change in the magnetic-field strength near a current coil while the
      drill stem and drill-stem joint successively pass through the current coil
      forward or backward. The detection system consists of a hardware subsystem and a
      software subsystem. The hardware subsystem employs a single-chip microprocessor
      as the main controller. A current coil is installed in front of the clamping
      unit, and two magneto resistive sensors are installed on the sides of the coil
      symmetrically and perpendicular to the direction of movement of the drill pipe.
      Their responses are used to judge whether the drill-stem joint is passing through
      the clamping unit; then, the order of their responses is used to judge the
      movement direction. The software subsystem is composed of a visual software
      running on the host computer and a software running in the slave microprocessor.
      The host-computer software processes, displays, and saves the drilling-length
      data, whereas the slave microprocessor software operates the hardware system. A
      combined test demonstrated the feasibility of the entire drilling-length
      detection system.

PMID- 28448444
TI  - Role of the Vanins-Myeloperoxidase Axis in Colorectal Carcinogenesis.
AB  - The presence of chronic inflammation in the colonic mucosa leads to an increased
      risk of cancer. Among proteins involved in the regulation of mucosal inflammation
      and that may contribute both to structural damage of the intestinal mucosa and to
      intestinal carcinogenesis, there are myeloperoxidase (MPO) and vanins. The
      infiltration of colonic mucosa by neutrophils may promote carcinogenesis through
      MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local
      inflammation and the generation of reactive oxygen species (ROS) and mutagenic
      species. The human vanin gene family consists of three genes: vanin-1, vanin-2
      and vanin-3. All vanin molecules are pantetheinases, that hydrolyze pantetheine
      into pantothenic acid (vitamin B5), and cysteamine, a sulfhydryl compound. Vanin
      1 loss confers an increased resistance to stress and acute intestinal
      inflammation, while vanin-2 regulates adhesion and transmigration of activated
      neutrophils. The metabolic product of these enzymes has a prominent role in the
      inflammation processes by affecting glutathione levels, inducing ulcers through a
      reduction in mucosal blood flow and oxygenation, decreasing local defense
      mechanisms, and in carcinogenesis by damaging DNA and regulating pathways
      involved in cell apoptosis, metabolism and growth, as Nrf2 and HIF-1alpha.

PMID- 28448446
TI  - Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK
      Signaling Pathways.
AB  - Renal interstitial fibrosis is a common pathway for the progression of chronic
      kidney disease (CKD) to end-stage renal disease. Renalase, acting as a signaling
      molecule, has been reported to have cardiovascular and renal protective effects.
      However, its role in renal fibrosis remains unknown. In this study, we evaluated
      the therapeutic efficacy of renalase in rats with complete unilateral ureteral
      obstruction (UUO) and examined the inhibitory effects of renalase on transforming
      growth factor-beta1 (TGF-beta1)-induced epithelial-mesenchymal transition (EMT)
      in human proximal renal tubular epithelial (HK-2) cells. We found that in the UUO
      model, the expression of renalase was markedly downregulated and adenoviral
      mediated expression of renalase significantly attenuated renal interstitial
      fibrosis, as evidenced by the maintenance of E-cadherin expression and suppressed
      expression of alpha-smooth muscle actin (alpha-SMA), fibronectin and collagen-I.
      In vitro, renalase inhibited TGF-beta1-mediated upregulation of alpha-SMA and
      downregulation of E-cadherin. Increased levels of Phospho-extracellular regulated
      protein kinases (p-ERK1/2) in TGF-beta1-stimulated cells were reversed by
      renalase cotreatment. When ERK1 was overexpressed, the inhibition of TGF-beta1
      induced EMT and fibrosis mediated by renalase was attenuated. Our study provides
      the first evidence that renalase can ameliorate renal interstitial fibrosis by
      suppression of tubular EMT through inhibition of the ERK pathway. These results
      suggest that renalase has potential renoprotective effects in renal interstitial
      fibrosis and may be an effective agent for slowing CKD progression.

PMID- 28448447
TI  - Factors Associated with Decreased Lean Tissue Index in Patients with Chronic
      Kidney Disease.
AB  - Muscle wasting is common and is associated with increased morbidity and mortality
      in patients with chronic kidney disease (CKD). However, factors associated with
      decreased muscle mass in CKD patients are seldom reported. We performed a cross
      sectional study of 326 patients (age 65.8 +/- 13.3 years) with stage 3-5 CKD who
      were not yet on dialysis. Muscle mass was determined using the Body Composition
      Monitor (BCM), a multifrequency bioimpedance spectroscopy device, and was
      expressed as the lean tissue index (LTI, lean tissue mass/height2). An LTI of
      less than 10% of the normal value (low LTI) indicates muscle wasting. Patients
      with low LTI (n = 40) tended to be diabetic, had significantly higher fat tissue
      index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis
      factor-alpha levels, but had significantly lower serum albumin and hemoglobin
      levels compared with those with normal LTI. In multivariate linear regression
      analysis, age, sex, cardiovascular disease, and interleukin-6 were independently
      associated with LTI. Additionally, diabetes mellitus remained an independent
      predictor of muscle wasting according to low LTI by multivariate logistic
      regression analysis. We conclude that LTI has important clinical correlations.
      Determination of LTI may aid in clinical assessment by helping to identify muscle
      wasting among patients with stage 3-5 CKD.

PMID- 28448449
TI  - An Artificial Measurements-Based Adaptive Filter for Energy-Efficient Target
      Tracking via Underwater Wireless Sensor Networks.
AB  - We study the problem of energy-efficient target tracking in underwater wireless
      sensor networks (UWSNs). Since sensors of UWSNs are battery-powered, it is
      impracticable to replace the batteries when exhausted. This means that the
      battery life affects the lifetime of the whole network. In order to extend the
      network lifetime, it is worth reducing the energy consumption on the premise of
      sufficient tracking accuracy. This paper proposes an energy-efficient filter that
      implements the tradeoff between communication cost and tracking accuracy. Under
      the distributed fusion framework, local sensors should not send their weak
      information to the fusion center if their measurement residuals are smaller than
      the pre-given threshold. In order to guarantee the target tracking accuracy,
      artificial measurements are generated to compensate for those unsent real
      measurements. Then, an adaptive scheme is derived to take full advantages of the
      artificial measurements-based filter in terms of energy-efficiency. Furthermore,
      a computationally efficient optimal sensor selection scheme is proposed to
      improve tracking accuracy on the premise of employing the same number of sensors.
      Simulation demonstrates that our scheme has superior advantages in the tradeoff
      between communication cost and tracking accuracy. It saves much energy while
      loosing little tracking accuracy or improves tracking performance with less
      additional energy cost.

PMID- 28448448
TI  - In Vitro, Ex Vivo and In Vivo Techniques to Study Neuronal Migration in the
      Developing Cerebral Cortex.
AB  - Neuronal migration is a fundamental biological process that underlies proper
      brain development and neuronal circuit formation. In the developing cerebral
      cortex, distinct neuronal populations, producing excitatory, inhibitory and
      modulatory neurotransmitters, are generated in different germinative areas and
      migrate along various routes to reach their final positions within the cortex.
      Different technical approaches and experimental models have been adopted to study
      the mechanisms regulating neuronal migration in the cortex. In this review, we
      will discuss the most common in vitro, ex vivo and in vivo techniques to
      visualize and study cortical neuronal migration.

PMID- 28448450
TI  - An Increased Understanding of Enolate Additions under Mechanochemical Conditions.
AB  - Very little is known about enolate addition chemistry under solver-free
      mechanochemical conditions. In this report, we investigated the ability to
      selectively form products arising from the primary, secondary, and tertiary
      enolates under solvent-free conditions. Using potassium tert-butoxide as the base
      and primary, secondary, and tertiary electrophiles, we were able to generate
      various enolate addition products including, 1,3,3,3-tetraphenyl-2,2-dimethyl-1
      propanone; a molecule we did not observe under traditional solution-based
      conditions.

PMID- 28448451
TI  - Time-Aware Service Ranking Prediction in the Internet of Things Environment.
AB  - With the rapid development of the Internet of things (IoT), building IoT systems
      with high quality of service (QoS) has become an urgent requirement in both
      academia and industry. During the procedures of building IoT systems, QoS-aware
      service selection is an important concern, which requires the ranking of a set of
      functionally similar services according to their QoS values. In reality, however,
      it is quite expensive and even impractical to evaluate all geographically
      dispersed IoT services at a single client to obtain such a ranking. Nevertheless,
      distributed measurement and ranking aggregation have to deal with the high
      dynamics of QoS values and the inconsistency of partial rankings. To address
      these challenges, we propose a time-aware service ranking prediction approach
      named TSRPred for obtaining the global ranking from the collection of partial
      rankings. Specifically, a pairwise comparison model is constructed to describe
      the relationships between different services, where the partial rankings are
      obtained by time series forecasting on QoS values. The comparisons of IoT
      services are formulated by random walks, and thus, the global ranking can be
      obtained by sorting the steady-state probabilities of the underlying Markov
      chain. Finally, the efficacy of TSRPred is validated by simulation experiments
      based on large-scale real-world datasets.

PMID- 28448452
TI  - A Wireless Sensor Network for Growth Environment Measurement and Multi-Band
      Optical Sensing to Diagnose Tree Vigor.
AB  - We have tried to develop the guidance system for farmers to cultivate using
      various phenological indices. As the sensing part of this system, we deployed a
      new Wireless Sensor Network (WSN). This system uses the 920 MHz radio wave based
      on the Wireless Smart Utility Network that enables long-range wireless
      communication. In addition, the data acquired by the WSN were standardized for
      the advanced web service interoperability. By using these standardized data, we
      can create a web service that offers various kinds of phenological indices as
      secondary information to the farmers in the field. We have also established the
      field management system using thermal image, fluorescent and X-ray fluorescent
      methods, which enable the nondestructive, chemical-free, simple, and rapid
      measurement of fruits or trees. We can get the information about the
      transpiration of plants through a thermal image. The fluorescence sensor gives us
      information, such as nitrate balance index (NBI), that shows the nitrate balance
      inside the leaf, chlorophyll content, flavonol content and anthocyanin content.
      These methods allow one to quickly check the health of trees and find ways to
      improve the tree vigor of weak ones. Furthermore, the fluorescent x-ray sensor
      has the possibility to quantify the loss of minerals necessary for fruit growth.

PMID- 28448454
TI  - Orthogonal Chirp-Based Ultrasonic Positioning.
AB  - This paper presents a chirp based ultrasonic positioning system (UPS) using
      orthogonal chirp waveforms. In the proposed method, multiple transmitters can
      simultaneously transmit chirp signals, as a result, it can efficiently utilize
      the entire available frequency spectrum. The fundamental idea behind the proposed
      multiple access scheme is to utilize the oversampling methodology of orthogonal
      frequency-division multiplexing (OFDM) modulation and orthogonality of the
      discrete frequency components of a chirp waveform. In addition, the proposed
      orthogonal chirp waveforms also have all the advantages of a classical chirp
      waveform. Firstly, the performance of the waveforms is investigated through
      correlation analysis and then, in an indoor environment, evaluated through
      simulations and experiments for ultrasonic (US) positioning. For an operational
      range of approximately 1000 mm, the positioning root-mean-square-errors (RMSEs)
      &90% error were 4.54 mm and 6.68 mm respectively.

PMID- 28448453
TI  - Working Memory in the Prefrontal Cortex.
AB  - The prefrontal cortex participates in a variety of higher cognitive functions.
      The concept of working memory is now widely used to understand prefrontal
      functions. Neurophysiological studies have revealed that stimulus-selective delay
      period activity is a neural correlate of the mechanism for temporarily
      maintaining information in working memory processes. The central executive, which
      is the master component of Baddeley's working memory model and is thought to be a
      function of the prefrontal cortex, controls the performance of other components
      by allocating a limited capacity of memory resource to each component based on
      its demand. Recent neurophysiological studies have attempted to reveal how
      prefrontal neurons achieve the functions of the central executive. For example,
      the neural mechanisms of memory control have been examined using the interference
      effect in a dual-task paradigm. It has been shown that this interference effect
      is caused by the competitive and overloaded recruitment of overlapping neural
      populations in the prefrontal cortex by two concurrent tasks and that the
      information-processing capacity of a single neuron is limited to a fixed level,
      can be flexibly allocated or reallocated between two concurrent tasks based on
      their needs, and enhances behavioral performance when its allocation to one task
      is increased. Further, a metamemory task requiring spatial information has been
      used to understand the neural mechanism for monitoring its own operations, and it
      has been shown that monitoring the quality of spatial information represented by
      prefrontal activity is an important factor in the subject's choice and that the
      strength of spatially selective delay-period activity reflects confidence in
      decision-making. Although further studies are needed to elucidate how the
      prefrontal cortex controls memory resource and supervises other systems, some
      important mechanisms related to the central executive have been identified.

PMID- 28448455
TI  - Snacking Quality Is Associated with Secondary School Academic Achievement and the
      Intention to Enroll in Higher Education: A Cross-Sectional Study in Adolescents
      from Santiago, Chile.
AB  - Although numerous studies have approached the effects of exposure to a Western
      diet (WD) on academic outcomes, very few have focused on foods consumed during
      snack times. We explored whether there is a link between nutritious snacking
      habits and academic achievement in high school (HS) students from Santiago,
      Chile. We conducted a cross-sectional study with 678 adolescents. The nutritional
      quality of snacks consumed by 16-year-old was assessed using a validated food
      frequency questionnaire. The academic outcomes measured were HS grade point
      average (GPA), the likelihood of HS completion, and the likelihood of taking
      college entrance exams. A multivariate analysis was performed to determine the
      independent associations of nutritious snacking with having completed HS and
      having taken college entrance exams. An analysis of covariance (ANCOVA) estimated
      the differences in GPA by the quality of snacks. Compared to students with
      healthy in-home snacking behaviors, adolescents having unhealthy in-home snacks
      had significantly lower GPAs (M difference: -40.1 points, 95% confidence interval
      (CI): -59.2, -16.9, d = 0.41), significantly lower odds of HS completion
      (adjusted odds ratio (aOR): 0.47; 95% CI: 0.25-0.88), and significantly lower
      odds of taking college entrance exams (aOR: 0.53; 95% CI: 0.31-0.88). Unhealthy
      at-school snacking showed similar associations with the outcome variables. Poor
      nutritional quality snacking at school and at home was associated with poor
      secondary school academic achievement and the intention to enroll in higher
      education.

PMID- 28448456
TI  - Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells
      Is Associated with Downregulation of NFKBIB and Increased Viral Survival.
AB  - Influenza A virus (IAV) infection remains a significant cause of morbidity and
      mortality worldwide. One key transcription factor that is activated upon IAV
      infection is nuclear factor Kappa B (NF-kappaB). NF-kappaB regulation involves
      the inhibitor proteins NF-kappaB inhibitor beta (NFKBIB), (also known as IkappaB
      beta), which form complexes with NF-kappaB to sequester it in the cytoplasm. In
      this study, microarray data showed differential expression of several microRNAs
      (miRNAs) on exposure to IAV. Target scan analysis revealed that miR-4776, miR
      4514 and miR-4742 potentially target NFKBIB messenger RNA (mRNA). Time-course
      analysis of primary bronchial epithelial cells (HBEpCs) showed that miR-4776
      expression is increased within 1 h of infection, followed by its downregulation 4
      h post-exposure to IAV. NFKBIB upregulation of miR-4776 correlated with a
      decrease in NFKBIB expression within 1 h of infection and a subsequent increase
      in NFKBIB expression 4 h post-infection. In addition, miRNA ago
      immunoprecipitation studies and the three prime untranslated region (3' UTR)
      luciferase assay confirmed that miR-4776 targets NFKBIB mRNA. Furthermore,
      uninfected HBEpCs transfected with miR-4776 mimic showed decreased expression of
      NFKBIB mRNA. Overexpression of NFKBIB protein in IAV infected cells led to lower
      levels of IAV. Taken together, our data suggest that miRNA-4776 modulates IAV
      production in infected cells through NFKBIB expression, possibly through the
      modulation of NF-kappaB.

PMID- 28448457
TI  - Effects of Vitamin D Supplementation on Bone Turnover Markers: A Randomized
      Controlled Trial.
AB  - Bone turnover markers (BTMs) are used to evaluate bone health together with bone
      mineral density and fracture assessment. Vitamin D supplementation is widely used
      to prevent and treat musculoskeletal diseases but existing data on vitamin D
      effects on markers of bone resorption and formation are inconsistent. We
      therefore examined the effects of vitamin D supplementation on bone-specific
      alkaline phosphatase (bALP), osteocalcin (OC), C-terminal telopeptide (CTX), and
      procollagen type 1 N-terminal propeptide (P1NP). This is a post-hoc analysis of
      the Styrian Vitamin D Hypertension Trial, a single-center, double-blind,
      randomized, placebo-controlled trial (RCT) performed at the Medical University of
      Graz, Austria (2011-2014). Two hundred individuals with arterial hypertension and
      25-hydroxyvitamin D (25[OH]D) levels <75 nmol/L were randomized to 2800 IU of
      vitamin D daily or placebo for eight weeks. One hundred ninety-seven participants
      (60.2 +/- 11.1 years; 47% women) were included in this analysis. Vitamin D had no
      significant effect on bALP (mean treatment effect (MTE) 0.013, 95% CI -0.029 to
      0.056 ug/L; p = 0.533), CTX (MTE 0.024, 95% CI -0.163 to 0.210 ng/mL, p = 0.802),
      OC (MTE 0.020, 95% CI -0.062 to 0.103 ng/mL, p = 0.626), or P1NP (MTE -0.021, 95%
      CI -0.099 to 0.057 ng/mL, p = 0.597). Analyzing patients with 25(OH)D levels <50
      nmol/L separately (n = 74) left results largely unchanged. In hypertensive
      patients with low 25(OH)D levels, we observed no significant effect of vitamin D
      supplementation for eight weeks on BTMs.

PMID- 28448458
TI  - Does an Empty Nest Affect Elders' Health? Empirical Evidence from China.
AB  - The "empty-nest" elderly family has become increasingly prevalent among old
      people in China. This study aimed to explore the causality between empty nests
      and elders' health using effective instrumental variables, including "whether old
      parents talk with their families when they are upset" and "ownership of housing".
      The results showed that empty nests had a significantly adverse influence on
      elders' physical health, cognitive ability and psychological health. Furthermore,
      urban elders' cognitive ability was more influenced by empty nests than that of
      rural elders. Additionally, the effects of an empty nest on elders" health were
      more significant among female, single elders and senior rural elders. "Living
      resources", "availability of medical treatment" and "social activity engagement"
      were found to be significant mediators between empty nests and elders' health,
      accounting for 35% of the total effect.

PMID- 28448459
TI  - Viability of Legionella pneumophila in Water Samples: A Comparison of Propidium
      Monoazide (PMA) Treatment on Membrane Filters and in Liquid.
AB  - Legionella pneumophila is a ubiquitous microorganism widely distributed in
      aquatic environments and can cause Legionellosis in humans. A promising approach
      to detect viable cells in water samples involves the use of quantitative
      polymerase chain reaction (qPCR) in combination with photoactivatable DNA
      intercalator propidium monoazide (PMA). However, the PMA efficiency could be
      different depending on the experimental conditions used. The aim of this study
      was to compare two PMA exposure protocols: (A) directly on the membrane filter or
      (B) in liquid after filter washing. The overall PMA-induced qPCR means reductions
      in heat-killed L. pneumophila cells were 2.42 and 1.91 log units for exposure
      protocols A and B, respectively. A comparison between the results obtained
      reveals that filter exposure allows a higher PMA-qPCR signal reduction to be
      reached, mainly at low concentrations (p < 0.05). This confirms the potential use
      of this method to quantify L. pneumophila in water with low contamination.

PMID- 28448460
TI  - Assessing Greenhouse Gas Emissions and Health Co-Benefits: A Structured Review of
      Lifestyle-Related Climate Change Mitigation Strategies.
AB  - This is the first structured review to identify and summarize research on
      lifestyle choices that improve health and have the greatest potential to mitigate
      climate change. Two literature searches were conducted on: (1) active transport
      health co-benefits, and (2) dietary health co-benefits. Articles needed to
      quantify both greenhouse gas emissions and health or nutrition outcomes resulting
      from active transport or diet changes. A data extraction tool (PRISMA) was
      created for article selection and evaluation. A rubric was devised to assess the
      biases, limitations and uncertainties of included articles. For active transport
      790 articles were retrieved, nine meeting the inclusion criteria. For diet 2524
      articles were retrieved, 23 meeting the inclusion criteria. A total of 31
      articles were reviewed and assessed using the rubric, as one article met the
      inclusion criteria for both active transport and diet co-benefits. Methods used
      to estimate the effect of diet or active transport modification vary greatly
      precluding meta-analysis. The scale of impact on health and greenhouse gas
      emissions (GHGE) outcomes depends predominately on the aggressiveness of the diet
      or active transport scenario modelled, versus the modelling technique. Effective
      mitigation policies, infrastructure that supports active transport and low GHGE
      food delivery, plus community engagement are integral in achieving optimal health
      and GHGE outcomes. Variation in culture, nutritional and health status, plus
      geographic density will determine which mitigation scenario(s) best suit
      individual communities.

PMID- 28448461
TI  - Prospective Study on the Impact of Fear of Falling on Functional Decline among
      Community Dwelling Elderly Women.
AB  - Fear of falling (FOF) is expected to have effects on functional decline in the
      elderly. In this study, we examined over 2 years the effect of change in FOF on
      functional decline in community dwelling elderly. We conducted a secondary
      analysis using data from elderly women, 70 years of age and older, who
      participated in the Korean Longitudinal Study of Aging (KLoSA). Participants were
      divided into four categories according to change in FOF between the 2010 and 2012
      surveys. Multiple logistic regression analysis was conducted regarding the
      effects of changes in FOF on functional decline after controlling for variables
      as known risk factors for functional decline. Rates of functional decline were
      highest in the "consistently having FOF" group, whereas they were lowest in the
      "consistently no FOF" group in both 2010 and 2012. Characteristics independently
      associated with functional decline were change in FOF, depressive symptoms, low
      frequency of meeting friends, and fear-induced activity avoidance. Longer
      exposure to FOF was associated with an increased risk of functional decline. FOF
      is an important health problem that deserves attention in its own right. Public
      health approaches for elderly persons should address early detection, prevention,
      and intervention programs for FOF.

PMID- 28448462
TI  - Targeting the ATR-CHK1 Axis in Cancer Therapy.
AB  - Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer
      that shows great promise for tumour selectivity. Key components of the DDR are
      the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1
      (CHK1) kinases. This review article describes the role of ATR and its major
      downstream target, CHK1, in the DDR and why cancer cells are particularly reliant
      on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and
      validation of this hypothesis by genetic manipulation. The recent development of
      specific inhibitors and preclinical data using these inhibitors not only as
      chemosensitisers and radiosensitisers but also as single agents to exploit
      specific pathologies of tumour cells is described. These potent and specific
      inhibitors have now entered clinical trial and early results are presented.

PMID- 28448464
TI  - Bayesian Device-Free Localization and Tracking in a Binary RF Sensor Network.
AB  - Received-signal-strength-based (RSS-based) device-free localization (DFL) is a
      promising technique since it is able to localize the person without attaching any
      electronic device. This technology requires measuring the RSS of all links in the
      network constituted by several radio frequency (RF) sensors. It is an energy
      intensive task, especially when the RF sensors work in traditional work mode, in
      which the sensors directly send raw RSS measurements of all links to a base
      station (BS). The traditional work mode is unfavorable for the power constrained
      RF sensors because the amount of data delivery increases dramatically as the
      number of sensors grows. In this paper, we propose a binary work mode in which RF
      sensors send the link states instead of raw RSS measurements to the BS, which
      remarkably reduces the amount of data delivery. Moreover, we develop two
      localization methods for the binary work mode which corresponds to stationary and
      moving target, respectively. The first localization method is formulated based on
      grid-based maximum likelihood (GML), which is able to achieve global optimum with
      low online computational complexity. The second localization method, however,
      uses particle filter (PF) to track the target when constant snapshots of link
      stats are available. Real experiments in two different kinds of environments were
      conducted to evaluate the proposed methods. Experimental results show that the
      localization and tracking performance under the binary work mode is comparable to
      the those in traditional work mode while the energy efficiency improves
      considerably.

PMID- 28448463
TI  - Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting
      Antioxidant, Inflammatory and Aromatase Expression.
AB  - Antioxidants have valuable effects on the process of spermatogenesis,
      particularly with diabetes mellitus (DM). Therefore, the present study
      investigated the impact and the intracellular mechanisms by which thymoquinone
      (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar
      male rats (n = 60) were randomly allocated into four groups; Control, Diabetic
      (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal
      injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50
      mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12
      weeks. Results revealed that TQ significantly improved the sperm parameters with
      a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular
      tissue. Also, it increased testicular reduced glutathione (GSH) levels and
      superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of
      testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF
      kappaB) and significantly upregulated the aromatase protein expression levels in
      testicles in comparison with the diabetic rats. In conclusion, TQ treatment
      exerted a protective effect against reproductive dysfunction induced by diabetes
      not only through its powerful antioxidant and hypoglycemic effects but also
      through its downregulation of testicular iNOS and NF-kappaB along with
      upregulation of aromatase expression levels in diabetic rats.

PMID- 28448465
TI  - Shadow-Based Vehicle Detection in Urban Traffic.
AB  - Vehicle detection is a fundamental task in Forward Collision Avoiding Systems
      (FACS). Generally, vision-based vehicle detection methods consist of two stages:
      hypotheses generation and hypotheses verification. In this paper, we focus on the
      former, presenting a feature-based method for on-road vehicle detection in urban
      traffic. Hypotheses for vehicle candidates are generated according to the shadow
      under the vehicles by comparing pixel properties across the vertical intensity
      gradients caused by shadows on the road, and followed by intensity thresholding
      and morphological discrimination. Unlike methods that identify the shadow under a
      vehicle as a road region with intensity smaller than a coarse lower bound of the
      intensity for road, the thresholding strategy we propose determines a coarse
      upper bound of the intensity for shadow which reduces false positives rates. The
      experimental results are promising in terms of detection performance and
      robustness in day time under different weather conditions and cluttered scenarios
      to enable validation for the first stage of a complete FACS.

PMID- 28448466
TI  - Multiplexed Electrochemical Immunosensors for Clinical Biomarkers.
AB  - Management and prognosis of disease requires the accurate determination of
      specific biomarkers indicative of normal or disease-related biological processes
      or responses to therapy. Moreover since multiple determinations of biomarkers
      have demonstrated to provide more accurate information than individual
      determinations to assist the clinician in prognosis and diagnosis, the detection
      of several clinical biomarkers by using the same analytical device hold enormous
      potential for early detection and personalized therapy and will simplify the
      diagnosis providing more information in less time. In this field, electrochemical
      immunosensors have demonstrated to offer interesting alternatives against
      conventional strategies due to their simplicity, fast response, low cost, high
      sensitivity and compatibility with multiplexed determination, microfabrication
      technology and decentralized determinations, features which made them very
      attractive for integration in point-of-care (POC) devices. Therefore, in this
      review, the relevance and current challenges of multiplexed determination of
      clinical biomarkers are briefly introduced, and an overview of the
      electrochemical immunosensing platforms developed so far for this purpose is
      given in order to demonstrate the great potential of these methodologies. After
      highlighting the main features of the selected examples, the unsolved challenges
      and future directions in this field are also briefly discussed.

PMID- 28448467
TI  - Chemical Composition and Biological Activities of Mono- and Heterofloral Bee
      Pollen of Different Geographical Origins.
AB  - Recent research shows variations in pollen chemical constituents and,
      consequently, in their therapeutic properties. Mono and multifloral bee pollen
      extracts were investigated for antioxidant and enzyme inhibitory activity
      properties, phenolic compounds and fatty acid composition. Generally, Eucalyptus
      spp. and multifloral extracts exhibited potent inhibitory activity against alpha
      amylase, acetylcholinesterase, tyrosinase, lipoxygenase, lipase and
      hyaluronidase. On the other hand, Miconia spp. demonstrated higher antihemolytic
      activity. Cocos nucifera and Miconia spp. extracts exhibited important
      antioxidant properties in the different assays (ABTS, DPPH, beta
      carotene/linoleic acid and reducing power). Moreover, these extracts had greater
      amounts of total phenols and flavonoids in comparison to others. The increase in
      antioxidant activity (decrease in EC50 values) was accompanied by an increase in
      the amount of total phenols in the extracts. The pollen extracts contained
      linoleic acid and alpha-linolenic acid as major fatty acids, followed by palmitic
      acid, and oleic acid. In this study, differences were observed in both chemical
      constituents and biological activities of the samples related to the geographical
      and botanical origin of bee pollen.

PMID- 28448469
TI  - Distributed Data Service for Data Management in Internet of Things Middleware.
AB  - The development of the Internet of Things (IoT) is closely related to a
      considerable increase in the number and variety of devices connected to the
      Internet. Sensors have become a regular component of our environment, as well as
      smart phones and other devices that continuously collect data about our lives
      even without our intervention. With such connected devices, a broad range of
      applications has been developed and deployed, including those dealing with
      massive volumes of data. In this paper, we introduce a Distributed Data Service
      (DDS) to collect and process data for IoT environments. One central goal of this
      DDS is to enable multiple and distinct IoT middleware systems to share common
      data services from a loosely-coupled provider. In this context, we propose a new
      specification of functionalities for a DDS and the conception of the
      corresponding techniques for collecting, filtering and storing data conveniently
      and efficiently in this environment. Another contribution is a data aggregation
      component that is proposed to support efficient real-time data querying. To
      validate its data collecting and querying functionalities and performance, the
      proposed DDS is evaluated in two case studies regarding a simulated smart home
      system, the first case devoted to evaluating data collection and aggregation when
      the DDS is interacting with the UIoT middleware, and the second aimed at
      comparing the DDS data collection with this same functionality implemented within
      the Kaa middleware.

PMID- 28448468
TI  - Transcriptome Analysis of Core Dinoflagellates Reveals a Universal Bias towards
      "GC" Rich Codons.
AB  - Although dinoflagellates are a potential source of pharmaceuticals and natural
      products, the mechanisms for regulating and producing these compounds are largely
      unknown because of extensive post-transcriptional control of gene expression. One
      well-documented mechanism for controlling gene expression during translation is
      codon bias, whereby specific codons slow or even terminate protein synthesis.
      Approximately 10,000 annotatable genes from fifteen "core" dinoflagellate
      transcriptomes along a range of overall guanine and cytosine (GC) content were
      used for codonW analysis to determine the relative synonymous codon usage (RSCU)
      and the GC content at each codon position. GC bias in the analyzed dataset and at
      the third codon position varied from 51% and 54% to 66% and 88%, respectively.
      Codons poor in GC were observed to be universally absent, but bias was most
      pronounced for codons ending in uracil followed by adenine (UA). GC bias at the
      third codon position was able to explain low abundance codons as well as the low
      effective number of codons. Thus, we propose that a bias towards codons rich in
      GC bases is a universal feature of core dinoflagellates, possibly relating to
      their unique chromosome structure, and not likely a major mechanism for
      controlling gene expression.

PMID- 28448470
TI  - Auxiliary Truncated Unscented Kalman Filtering for Bearings-Only Maneuvering
      Target Tracking.
AB  - Novel auxiliary truncated unscented Kalman filtering (ATUKF) is proposed for
      bearings-only maneuvering target tracking in this paper. In the proposed
      algorithm, to deal with arbitrary changes in motion models, a modified prior
      probability density function (PDF) is derived based on some auxiliary target
      characteristics and current measurements. Then, the modified prior PDF is
      approximated as a Gaussian density by using the statistical linear regression
      (SLR) to estimate the mean and covariance. In order to track bearings-only
      maneuvering target, the posterior PDF is jointly estimated based on the prior
      probability density function and the modified prior probability density function,
      and a practical algorithm is developed. Finally, compared with other nonlinear
      filtering approaches, the experimental results of the proposed algorithm show a
      significant improvement for both the univariate nonstationary growth model (UNGM)
      case and bearings-only target tracking case.

PMID- 28448472
TI  - Vibro-Shock Dynamics Analysis of a Tandem Low Frequency Resonator-High Frequency
      Piezoelectric Energy Harvester.
AB  - Frequency up-conversion is a promising technique for energy harvesting in low
      frequency environments. In this approach, abundantly available environmental
      motion energy is absorbed by a Low Frequency Resonator (LFR) which transfers it
      to a high frequency Piezoelectric Vibration Energy Harvester (PVEH) via impact or
      magnetic coupling. As a result, a decaying alternating output signal is produced,
      that can later be collected using a battery or be transferred directly to the
      electric load. The paper reports an impact-coupled frequency up-converting tandem
      setup with different LFR to PVEH natural frequency ratios and varying contact
      point location along the length of the harvester. RMS power output of different
      frequency up-converting tandems with optimal resistive values was found from the
      transient analysis revealing a strong relation between power output and LFR-PVEH
      natural frequency ratio as well as impact point location. Simulations revealed
      that higher power output is obtained from a higher natural frequency ratio
      between LFR and PVEH, an increase of power output by one order of magnitude for a
      doubled natural frequency ratio and up to 150% difference in power output from
      different impact point locations. The theoretical results were experimentally
      verified.

PMID- 28448471
TI  - Regulation of G Protein-Coupled Receptors by Ubiquitination.
AB  - G protein-coupled receptors (GPCRs) comprise the largest family of membrane
      receptors that control many cellular processes and consequently often serve as
      drug targets. These receptors undergo a strict regulation by mechanisms such as
      internalization and desensitization, which are strongly influenced by
      posttranslational modifications. Ubiquitination is a posttranslational
      modification with a broad range of functions that is currently gaining increased
      appreciation as a regulator of GPCR activity. The role of ubiquitination in
      directing GPCRs for lysosomal degradation has already been well-established.
      Furthermore, this modification can also play a role in targeting membrane and
      endoplasmic reticulum-associated receptors to the proteasome. Most recently,
      ubiquitination was also shown to be involved in GPCR signaling. In this review,
      we present current knowledge on the molecular basis of GPCR regulation by
      ubiquitination, and highlight the importance of E3 ubiquitin ligases,
      deubiquitinating enzymes and beta-arrestins. Finally, we discuss classical and
      newly-discovered functions of ubiquitination in controlling GPCR activity.

PMID- 28448473
TI  - Transcriptomic Analysis of Calcium Remodeling in Colorectal Cancer.
AB  - Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca2+
      homeostasis, which contributes to cancer hallmarks such as enhanced
      proliferation, invasion and survival. Ca2+ remodeling includes critical changes
      in store-operated Ca2+ entry (SOCE) and Ca2+ store content. Some changes have
      been investigated at the molecular level. However, since nearly 100 genes are
      involved in intracellular Ca2+ transport, a comprehensive view of Ca2+ remodeling
      in CRC is lacking. We have used Next Generation Sequencing (NGS) to investigate
      differences in expression of 77 selected gene transcripts involved in
      intracellular Ca2+ transport in CRC. To this end, mRNA from normal human colonic
      NCM460 cells and human colon cancer HT29 cells was isolated and used as a
      template for transcriptomic sequencing and expression analysis using Ion Torrent
      technology. After data transformation and filtering, exploratory analysis
      revealed that both cell types were well segregated. In addition, differential
      gene expression using R and bioconductor packages show significant differences in
      expression of selected voltage-operated Ca2+ channels and store-operated Ca2+
      entry players, transient receptor potential (TRP) channels, Ca2+ release
      channels, Ca2+ pumps, Na+/Ca2+ exchanger isoforms and genes involved in
      mitochondrial Ca2+ transport. These data provide the first comprehensive
      transcriptomic analysis of Ca2+ remodeling in CRC.

PMID- 28448474
TI  - Innovative "Green" and Novel Strategies for the Extraction of Bioactive Added
      Value Compounds from Citrus Wastes-A Review.
AB  - Citrus is a major processed crop that results in large quantities of wastes and
      by-products rich in various bioactive compounds such as pectins, water soluble
      and insoluble antioxidants and essential oils. While some of those wastes are
      currently valorised by various technologies (yet most are discarded or used for
      feed), effective, non-toxic and profitable extraction strategies could further
      significantly promote the valorisation and provide both increased profits and
      high quality bioactives. The present review will describe and summarize the
      latest works concerning novel and greener methods for valorisation of citrus by
      products. The outcomes and effectiveness of those technologies such as
      microwaves, ultrasound, pulsed electric fields and high pressure is compared both
      to conventional valorisation technologies and between the novel technologies
      themselves in order to highlight the advantages and potential scalability of
      these so-called "enabling technologies". In many cases the reported novel
      technologies can enable a valorisation extraction process that is "greener"
      compared to the conventional technique due to a lower energy consumption and
      reduced utilization of toxic solvents.

PMID- 28448475
TI  - Formulation, Characterization and Properties of Hemp Seed Oil and Its Emulsions.
AB  - The formulation, characterization, and anticipated antibacterial properties of
      hemp seed oil and its emulsions were investigated. The oil obtained from the
      seeds of Cannabis sativa L. in refined and unrefined form was characterized using
      iodine, saponification, acid values, and gas chromatography, and was employed for
      the preparation of stable oil-in-water emulsions. The emulsions were prepared
      using pairs of non-ionic surfactants (Tween, Span). The effects of the
      emulsification method (spontaneous emulsification vs. high-intensity stirring),
      hydrophilic lipophilic balance (HLB), type and concentration of surfactant, and
      oil type on the size and distribution of the emulsion particles were
      investigated. It was found that the ability to form stable emulsions with small,
      initial particle sizes is primarily dependent on the given method of preparation
      and the HLB value. The most efficient method of emulsification that afforded the
      best emulsions with the smallest particles (151 +/- 1 nm) comprised the high
      energy method, and emulsions stable over the long-term were observed at HBL 9
      with 10 wt % concentration of surfactants. Under high-intensity emulsification,
      refined and unrefined oils performed similarly. The oils as well as their
      emulsions were tested against the growth of selected bacteria using the disk
      diffusion and broth microdilution methods. The antibacterial effect of hemp seed
      oil was documented against Micrococcus luteus and Staphylococcus aureus subsp.
      aureus. The formulated emulsions did not exhibit the antibacterial activity that
      had been anticipated.

PMID- 28448476
TI  - Special Issue "Structure-Activity Relationship of Natural Products".

PMID- 28448478
TI  - QuickStats: Percentage* of Adult Workers Aged >=18 Years Who Reported Being
      Threatened, Bullied, or Harassed While on the Job,? by Sex - National Health
      Interview Survey, United States, 2010 and 2015S.

PMID- 28448477
TI  - Evaluation of Gelatin Tannate Against Symptoms of Acute Diarrhea in Pediatric
      Patients.
AB  - BACKGROUND Acute diarrhea is the second most common cause of morbidity and
      mortality worldwide, especially in children aged <=3 years. Some drugs (e.g., the
      mucoprotector gelatin tannate) plus a reduced osmolality oral rehydration
      solution (ORS) may effectively reduce symptom duration and severity. The current
      trial was therefore designed to assess the efficacy and safety of gelatin tannate
      in pediatric patients with acute diarrhea. MATERIAL AND METHODS This was a
      randomized, controlled, double-blind, parallel-group, single-center study
      comparing gelatin tannate plus ORS (103 patients) with ORS plus placebo (100
      patients) in children aged 3 months to 12 years with infectious or noninfectious
      acute diarrhea. Details about stool consistency and total time to resolution of
      diarrhea comprised the primary study endpoints. Secondary study endpoints
      included symptoms of diarrhea at 12, 24, 36, 48, and 72 hours after the first
      dose of study medication. RESULTS From 12 hours onwards, the incidence of watery
      stools was significantly lower in the gelatin tannate group than in the ORS group
      (at 12 hours: 59.2% vs. 77.0%; p=0.01). The same was true for stool frequency (at
      12 hours: mean 2 vs. 3 stool productions in the previous 12 hours; p<0.01). At
      all timepoints during the study, the proportion of patients with Stool Decrease
      Index improvement was significantly greater (p<0.01) in the gelatin tannate group
      than in the placebo group (at 12 hours: 66.6% vs. 33.3%; p<0.01). CONCLUSIONS
      Gelatin tannate plus ORS is an effective and safe option for the treatment of
      acute diarrhea in children. Significant symptom relief is evident 12 hours after
      starting treatment.

PMID- 28448479
TI  - Announcement: Community Preventive Services Task Force Recommends Interventions
      to Increase Healthier Foods and Beverages in Schools.

PMID- 28448480
TI  - Announcement: National Campaign to Prevent Falls in Construction - United States,
      2017.

PMID- 28448481
TI  - Occupational Fatalities Resulting from Falls in the Oil and Gas Extraction
      Industry, United States, 2005-2014.
AB  - During 2003-2013, fatality rates for oil and gas extraction workers decreased for
      all causes of death except those associated with fall events, which increased 2%
      annually during 2003-2013 (1). To better understand risk factors for these
      events, CDC examined fatal fall events in the oil and gas extraction industry
      during 2005-2014 using data from case investigations conducted by the
      Occupational Safety and Health Administration (OSHA). Sixty-three fatal falls
      were identified, accounting for 15% of all fatal events. Among fatal falls, 33
      (52%) workers fell from a height of >30 feet (9 meters), and 22 (35%) fell from
      the derrick board, the elevated work platform located in the derrick (structure
      used to support machinery on a drilling rig). Fall fatalities occurred most
      frequently when drilling rigs were being assembled or disassembled at the well
      site (rigging up or rigging down) (14; 22%) or when workers were removing or
      inserting drill pipe into the wellbore (14; 22%). Measures that target derrickmen
      and workers engaged in assembling and disassembling drilling rigs (rigging up and
      down) could reduce falls in this industry. Companies should annually update their
      fall protection plans and ensure effective fall prevention programs are in place
      for workers at highest risk for falls, including providing trainings on proper
      use, fit, and inspection of personal protective equipment.

PMID- 28448482
TI  - Diabetes Self-Management Education Programs in Nonmetropolitan Counties - United
      States, 2016.
AB  - PROBLEM/CONDITION: Diabetes self-management education (DSME) is a clinical
      practice intended to improve preventive practices and behaviors with a focus on
      decision-making, problem-solving, and self-care. The distribution and correlates
      of established DSME programs in nonmetropolitan counties across the United States
      have not been previously described, nor have the characteristics of the
      nonmetropolitan counties with DSME programs. REPORTING PERIOD: July 2016.
      DESCRIPTION OF SYSTEMS: DSME programs recognized by the American Diabetes
      Association or accredited by the American Association of Diabetes Educators
      (i.e., active programs) as of July 2016 were shared with CDC by both
      organizations. The U.S. Census Bureau's census geocoder was used to identify the
      county of each DSME program site using documented addresses. County
      characteristic data originated from the U.S. Census Bureau, compiled by the U.S.
      Department of Agriculture's Economic Research Service into the 2013 Atlas of
      Rural and Small-Town America data set. County levels of diagnosed diabetes
      prevalence and incidence, as well as the number of persons with diagnosed
      diabetes, were previously estimated by CDC. This report defined nonmetropolitan
      counties using the rural-urban continuum code from the 2013 Atlas of Rural and
      Small-Town America data set. This code included six nonmetropolitan categories of
      1,976 urban and rural counties (62% of counties) adjacent to and nonadjacent to
      metropolitan counties. RESULTS: In 2016, a total of 1,065 DSME programs were
      located in 38% of the 1,976 nonmetropolitan counties; 62% of nonmetropolitan
      counties did not have a DSME program. The total number of DSME programs for
      nonmetropolitan counties with at least one DSME program ranged from 1 to 8, with
      an average of 1.4 programs. After adjusting for county-level characteristics, the
      odds of a nonmetropolitan county having at least one DSME program increased as
      the percentage insured increased (adjusted odds ratio [AOR] = 1.10, 95%
      confidence interval [CI] = 1.08-1.13), the percentage with a high school
      education or less decreased (AOR = 1.06, 95% CI = 1.04-1.07), the unemployment
      rate decreased (AOR = 1.19, 95% CI = 1.11-1.23), and the natural logarithm of the
      number of persons with diabetes increased (AOR = 3.63, 95% CI = 3.15-4.19).
      INTERPRETATION: In 2016, there were few DMSE programs in nonmetropolitan,
      socially disadvantaged counties in the United States. The number of persons with
      diabetes, percentage insured, percentage with a high school education or less,
      and the percentage unemployed were significantly associated with whether a DSME
      program was located in a nonmetropolitan county. PUBLIC HEALTH ACTION: Monitoring
      the distribution of DSME programs at the county level provides insight needed to
      strategically address rural disparities in diabetes care and outcomes. These
      findings provide information needed to assess lack of availability of DSME
      programs and to explore evidence-based strategies and innovative technologies to
      deliver DSME programs in underserved rural communities.

PMID- 28448483
TI  - Trends in Repeat Births and Use of Postpartum Contraception Among Teens - United
      States, 2004-2015.
AB  - Teen* childbearing (one or more live births before age 20 years) can have
      negative health, social, and economic consequences for mothers and their children
      (1). Repeat teen births (two or more live births before age 20 years) can
      constrain the mother's ability to take advantage of educational and workforce
      opportunities (2), and are more likely to be preterm or of low birthweight than
      first teen births (3). Despite the historic decline in the U.S. teen birth rate
      during 1991-2015, from 61.8 to 22.3 births per 1,000 females aged 15-19 years
      (4), many teens continue to have repeat births (3). The American College of
      Obstetricians and Gynecologists and the American Academy of Pediatrics both
      recommend that clinicians counsel women (including teens) during prenatal care
      about birth spacing and postpartum contraceptive use (5), including the safety
      and effectiveness of long-acting reversible methods that can be initiated
      immediately postpartum. To expand upon prior research assessing patterns and
      trends in repeat childbearing and postpartum contraceptive use among teens with a
      recent live birth (i.e., 2-6 months after delivery) (3), CDC analyzed data from
      the National Vital Statistics System natality files (2004 and 2015) and the
      Pregnancy Risk Assessment Monitoring System (PRAMS; 2004-2013). The number and
      proportion of teen births that were repeat births decreased from 2004 (82,997;
      20.1%) to 2015 (38,324; 16.7%); in 2015, the percentage of teen births that were
      repeat births varied by state from 10.6% to 21.4%. Among sexually active teens
      with a recent live birth, postpartum use of the most effective contraceptive
      methods (intrauterine devices and contraceptive implants) increased from 5.3% in
      2004 to 25.3% in 2013; however, in 2013, approximately one in three reported
      using either a least effective method (15.7%) or no method (17.2%). Strategies
      that comprehensively address the social and health care needs of teen parents can
      facilitate access to and use of effective methods of contraception and help
      prevent repeat teen births.

PMID- 28448484
TI  - Tissue-engineered 3D human lymphatic microvascular network for in vitro studies
      of lymphangiogenesis.
AB  - This protocol describes a unique in vitro method for the generation of a 3D human
      lymphatic network within native connective tissue devoid of any exogenous
      material such as scaffolds or growth factors. In this five-stage protocol, human
      lymphatic endothelial cells (LECs) cocultured with dermal fibroblasts
      spontaneously organize into a stable 3D lymphatic capillary network. Stage 1
      involves the isolation of primary fibroblasts and LECs from human skin.
      Fibroblasts are then cultured to produce connective tissue rich in extracellular
      matrix (stage 2), onto which LECs are seeded to form a network (stage 3). After
      stacking of tissue layers and tissue maturation at the air-liquid interface
      (stage 4), the 3D construct containing the lymphatic microvascular network can be
      analyzed by microscopy (stage 5). Lymphatic vasculature generated by this
      approach exhibits the major cellular and ultrastructural features of native in
      vivo human dermal lymphatic microvasculature and is stable over many weeks. The
      protocol for generating a 3D construct takes 6 weeks to complete, and it requires
      experience in cell culture techniques. The system described here offers a unique
      opportunity to study the mechanisms underlying lymphatic vessel formation,
      remodeling and function in a human cell context.

PMID- 28448485
TI  - Assessment of engineered cells using CellNet and RNA-seq.
AB  - CellNet is a computational platform designed to assess cell populations
      engineered by either directed differentiation of pluripotent stem cells (PSCs) or
      direct conversion, and to suggest specific hypotheses to improve cell fate
      engineering protocols. CellNet takes as input gene expression data and compares
      them with large data sets of normal expression profiles compiled from public
      sources, in regard to the extent to which cell- and tissue-specific gene
      regulatory networks are established. CellNet was originally designed to work with
      human or mouse microarray expression data for 21 cell or tissue (C/T) types. Here
      we describe how to apply CellNet to RNA-seq data and how to build a completely
      new CellNet platform applicable to, for example, other species or additional cell
      and tissue types. Once the raw data have been preprocessed, running CellNet takes
      only several minutes, whereas the time required to create a completely new
      CellNet is several hours.

PMID- 28448486
TI  - [First Mexican Consensus of Vaccination in Adults].
AB  - For years our efforts have been focused on vaccination during childhood. Today we
      know that this is not enough to ensure health in the rest of the life. Childhood
      is as important as any other stage and, therefore, vaccination must be permanent
      and differentiated, according to our age, throughout life. Introducing a life
      course perspective in vaccination programs, with emphasis on adult vaccination,
      particularly in older adults, offers us the opportunity to review the performance
      of health programs, actions, and services in the field of immunization, as well
      as strengthening health promotion actions. In this context, the first Mexican
      Consensus on Adult Vaccination was carried out in a joint effort of the National
      Institute of Geriatrics, bringing together a group of specialists who worked on
      three central objectives: establishing vaccination guidelines throughout the life
      course, with emphasis on new vaccines; defining priority groups according to
      their risk factors; and contributing to the effort to promote healthy aging.

PMID- 28448487
TI  - The first "London Declaration": The Commonwealth and its neglected tropical
      diseases.

PMID- 28448488
TI  - The potential economic burden of Zika in the continental United States.
AB  - BACKGROUND: As the Zika virus epidemic continues to spread internationally,
      countries such as the United States must determine how much to invest in
      prevention, control, and response. Fundamental to these decisions is quantifying
      the potential economic burden of Zika under different scenarios.
      METHODOLOGY/PRINCIPLE FINDINGS: To inform such decision making, our team
      developed a computational model to forecast the potential economic burden of Zika
      across six states in the US (Alabama, Florida, Georgia, Louisiana, Mississippi,
      and Texas) which are at greatest risk of Zika emergence, under a wide range of
      attack rates, scenarios and circumstances. In order to accommodate a wide range
      of possibilities, different scenarios explored the effects of varying the attack
      rate from 0.01% to 10%. Across the six states, an attack rate of 0.01% is
      estimated to cost $183.4 million to society ($117.1 million in direct medical
      costs and $66.3 million in productivity losses), 0.025% would result in $198.6
      million ($119.4 million and $79.2 million), 0.10% would result in $274.6 million
      ($130.8 million and $143.8 million) and 1% would result in $1.2 billion ($268.0
      million and $919.2 million). CONCLUSIONS: Our model and study show how direct
      medical costs, Medicaid costs, productivity losses, and total costs to society
      may vary with different attack rates across the six states and the circumstances
      at which they may exceed certain thresholds (e.g., Zika prevention and control
      funding allocations that are being debated by the US government). A Zika attack
      rate of 0.3% across the six states at greatest risk of Zika infection, would
      result in total costs that exceed $0.5 billion, an attack rate of 1% would exceed
      $1 billion, and an attack rate of 2% would exceed $2 billion.

PMID- 28448489
TI  - Determinants of severe dehydration from diarrheal disease at hospital
      presentation: Evidence from 22 years of admissions in Bangladesh.
AB  - BACKGROUND: To take advantage of emerging opportunities to reduce morbidity and
      mortality from diarrheal disease, we need to better understand the determinants
      of life-threatening severe dehydration (SD) in resource-poor settings.
      METHODOLOGY/FINDINGS: We analyzed records of patients admitted with acute
      diarrheal disease over twenty-two years at the International Centre for
      Diarrhoeal Disease Research, Bangladesh (1993-2014). Patients presenting with and
      without SD were compared by multivariable logistic regression models, which
      included socio-demographic factors and pathogens isolated. Generalized additive
      models evaluated non-linearities between age or household income and SD. Among
      55,956 admitted patients, 13,457 (24%) presented with SD. Vibrio cholerae was the
      most common pathogen isolated (12,405 patients; 22%), and had the strongest
      association with SD (AOR 4.77; 95% CI: 4.41-5.51); detection of multiple
      pathogens did not exacerbate SD risk. The highest proportion of severely
      dehydrated patients presented in a narrow window only 4-12 hours after symptom
      onset. Risk of presenting with SD increased sharply from zero to ten years of age
      and remained high throughout adolescence and adulthood. Adult women had a 38%
      increased odds (AOR 1.38; 95% CI: 1.30-1.46) of SD compared to adult men. The
      probability of SD increased sharply at low incomes. These findings were
      consistent across pathogens. CONCLUSIONS/SIGNIFICANCE: There remain
      underappreciated populations vulnerable to life-threatening diarrheal disease
      that include adult women and the very poor. In addition to efforts that address
      diarrheal disease in young children, there is a need to develop interventions for
      these other high-risk populations that are accessible within 4 hours of symptom
      onset.

PMID- 28448490
TI  - The value of daily platelet counts for predicting dengue shock syndrome: Results
      from a prospective observational study of 2301 Vietnamese children with dengue.
AB  - BACKGROUND: Dengue is the most important mosquito-borne viral infection to affect
      humans. Although it usually manifests as a self-limited febrile illness,
      complications may occur as the fever subsides. A systemic vascular leak syndrome
      that sometimes progresses to life-threatening hypovolaemic shock is the most
      serious complication seen in children, typically accompanied by
      haemoconcentration and thrombocytopenia. Robust evidence on risk factors,
      especially features present early in the illness course, for progression to
      dengue shock syndrome (DSS) is lacking. Moreover, the potential value of
      incorporating serial haematocrit and platelet measurements in prediction models
      has never been assessed. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from a
      prospective observational study of Vietnamese children aged 5-15 years admitted
      with clinically suspected dengue to the Hospital for Tropical Diseases in Ho Chi
      Minh City between 2001 and 2009. The analysis population comprised all children
      with laboratory-confirmed dengue enrolled between days 1-4 of illness. Logistic
      regression was the main statistical model for all univariate and multivariable
      analyses. The prognostic value of daily haematocrit levels and platelet counts
      were assessed using graphs and separate regression models fitted on each day of
      illness. Among the 2301 children included in the analysis, 143 (6%) progressed to
      DSS. Significant baseline risk factors for DSS included a history of vomiting,
      higher temperature, a palpable liver, and a lower platelet count. Prediction
      models that included serial daily platelet counts demonstrated better ability to
      discriminate patients who developed DSS from others, than models based on
      enrolment information only. However inclusion of daily haematocrit values did not
      improve prediction of DSS. CONCLUSIONS/SIGNIFICANCE: Daily monitoring of platelet
      counts is important to help identify patients at high risk of DSS. Development of
      dynamic prediction models that incorporate signs, symptoms, and daily laboratory
      measurements, could improve DSS prediction and thereby reduce the burden on
      health services in endemic areas.

PMID- 28448491
TI  - Relevant units of analysis for applied and basic research dealing with neglected
      transmissible diseases: The predominant clonal evolution model of pathogenic
      microorganisms.
AB  - The predominant clonal evolution (PCE) model seeks to formulate a common
      population genetics framework for all micropathogens (namely, parasitic protozoa,
      fungi and yeasts, bacteria, and viruses). It relies on a definition of clonality
      that is only based on population structure features (namely, strongly restrained
      genetic recombination). Its clear-cut properties make it of strong interest for
      applied and basic research, since it permits the definition of stable, clearly
      delimited units of analysis below the species level: clonal genotypes and
      discrete genetic subdivisions ("near-clades"). These units of analysis can be
      used for clinical and epidemiological studies, vaccine and drug design, species
      description, and evolutionary studies on natural and experimental populations. In
      this review, the evolutionary and population genetics background of the model
      will be only briefly mentioned, while considerable emphasis will be given to its
      practical significance for the study and control of neglected tropical diseases.
      The goal of the paper is to make this practical usefulness accessible to a broad
      audience of readers, including scientists who are not evolution specialists, such
      as epidemiologists, field scientists, and clinicians. For extensive developments
      about the evolutionary background of the model, see our previous papers [1-9].
      Citations of these former articles lead to the many references quoted in them,
      which cannot be listed again here.

PMID- 28448492
TI  - Stylized facts of intraday precious metals.
AB  - This paper examines the stylized facts, correlation and interaction between
      volatility and returns at the 5-minute frequency for gold, silver, platinum and
      palladium from May 2000 to April 2015. We study the full sample period, as well
      as three subsamples to determine how high-frequency data of precious metals have
      developed over time. We find that over the full sample, the number of trades has
      increased substantially over time for each precious metal, while the bid-ask
      spread has narrowed over time, indicating an increase in liquidity and price
      efficiency. We also find strong evidence of periodicity in returns, volatility,
      volume and bid-ask spread. Returns and volume both experience strong intraday
      periodicity linked to the opening and closing of major markets around the world
      while the bid-ask spread is at its lowest when European markets are open. We also
      show a bilateral Granger causality between returns and volatility of each
      precious metal, which holds for the vast majority subsamples.

PMID- 28448493
TI  - Variable habitat conditions drive species covariation in the human microbiota.
AB  - Two species with similar resource requirements respond in a characteristic way to
      variations in their habitat-their abundances rise and fall in concert. We use
      this idea to learn how bacterial populations in the microbiota respond to habitat
      conditions that vary from person-to-person across the human population. Our
      mathematical framework shows that habitat fluctuations are sufficient for
      explaining intra-bodysite correlations in relative species abundances from the
      Human Microbiome Project. We explicitly show that the relative abundances of
      closely related species are positively correlated and can be predicted from
      taxonomic relationships. We identify a small set of functional pathways related
      to metabolism and maintenance of the cell wall that form the basis of a common
      resource sharing niche space of the human microbiota.

PMID- 28448494
TI  - Integrin beta1 activation induces an anti-melanoma host response.
AB  - TGF-beta is a cytokine thought to function as a tumor promoter in advanced
      malignancies. In this setting, TGF-beta increases cancer cell proliferation,
      survival, and migration, and orchestrates complex, pro-tumorigenic changes in the
      tumor microenvironment. Here, we find that in melanoma, integrin beta1-mediated
      TGF-beta activation may also produce tumor suppression via an altered host
      response. In the A375 human melanoma cell nu/nu xenograft model, we demonstrate
      that cell surface integrin beta1-activation increases TGF-beta activity,
      resulting in stromal activation, neo-angiogenesis and, unexpectedly for this nude
      mouse model, increase in the number of intra-tumoral CD8+ T lymphocytes within
      the tumor microenvironment. This is associated with attenuation of tumor growth
      and long-term survival benefit. Correspondingly, in human melanomas, TGF-beta1
      correlates with integrin beta1/TGF-beta1 activation and the expression of markers
      for vasculature and stromal activation. Surprisingly, this integrin beta1/TGF
      beta1 transcriptional footprint also correlates with the expression of markers
      for tumor-infiltrating lymphocytes, multiple immune checkpoints and regulatory
      pathways, and, importantly, better long-term survival of patients. These
      correlations are unique to melanoma, in that we do not observe similar
      associations between beta1 integrin/TGF-beta1 activation and better long-term
      survival in other human tumor types. These results suggest that activation of TGF
      beta1 in melanoma may be associated with the generation of an anti-tumor host
      response that warrants further study.

PMID- 28448496
TI  - Correction: Spatial separation of two different pathways accounting for the
      generation of calcium signals in astrocytes.
AB  - [This corrects the article DOI: 10.1371/journal.pcbi.1005377.].

PMID- 28448495
TI  - Dysregulation of INF2-mediated mitochondrial fission in SPOP-mutated prostate
      cancer.
AB  - Next-generation sequencing of the exome and genome of prostate cancers has
      identified numerous genetic alternations. SPOP (Speckle-type POZ Protein) was one
      of the most frequently mutated genes in primary prostate cancer, suggesting SPOP
      is a potential driver of prostate cancer development and progression. However,
      how SPOP mutations contribute to prostate cancer pathogenesis remains poorly
      understood. SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase
      complex that generally recruits substrates for ubiquitination and subsequent
      degradation. ER-localized isoform of the formin protein inverted formin 2 (INF2)
      mediates actin polymerization at ER-mitochondria intersections and facilitates
      DRP1 recruitment to mitochondria, which is a critical step in mitochondrial
      fission. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the
      C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These
      ubiquitination modifications do not lead to INF2 instability, but rather reduces
      INF2 localization in ER and mitochondrially associated DRP1 puncta formation,
      therefore abrogates its ability to facilitate mitochondrial fission. INF2 mutant
      escaping from SPOP-mediated ubiquitination is more potent in prompting
      mitochondrial fission. Moreover, prostate cancer-associated SPOP mutants increase
      INF2 localization in ER and promote mitochondrial fission, probably through a
      dominant-negative effect to inhibit endogenous SPOP. Moreover, INF2 is important
      for SPOP inactivation-induced prostate cancer cell migration and invasion. These
      findings reveal novel molecular events underlying the regulation of INF2 function
      and localization, and provided insights in understanding the relationship between
      SPOP mutations and dysregulation of mitochondrial dynamics in prostate cancer.

PMID- 28448497
TI  - Examination of an eHealth literacy scale and a health literacy scale in a
      population with moderate to high cardiovascular risk: Rasch analyses.
AB  - INTRODUCTION: Electronic health (eHealth) strategies are evolving making it
      important to have valid scales to assess eHealth and health literacy. Item
      response theory methods, such as the Rasch measurement model, are increasingly
      used for the psychometric evaluation of scales. This paper aims to examine the
      internal construct validity of an eHealth and health literacy scale using Rasch
      analysis in a population with moderate to high cardiovascular disease risk.
      METHODS: The first 397 participants of the CONNECT study completed the electronic
      health Literacy Scale (eHEALS) and the Health Literacy Questionnaire (HLQ).
      Overall Rasch model fit as well as five key psychometric properties were
      analysed: unidimensionality, response thresholds, targeting, differential item
      functioning and internal consistency. RESULTS: The eHEALS had good overall model
      fit (chi2 = 54.8, p = 0.06), ordered response thresholds, reasonable targeting
      and good internal consistency (person separation index (PSI) 0.90). It did,
      however, appear to measure two constructs of eHealth literacy. The HLQ subscales
      (except subscale 5) did not fit the Rasch model (chi2: 18.18-60.60, p: 0.00-0.58)
      and had suboptimal targeting for most subscales. Subscales 6 to 9 displayed
      disordered thresholds indicating participants had difficulty distinguishing
      between response options. All subscales did, nonetheless, demonstrate moderate to
      good internal consistency (PSI: 0.62-0.82). CONCLUSION: Rasch analyses
      demonstrated that the eHEALS has good measures of internal construct validity
      although it appears to capture different aspects of eHealth literacy (e.g. using
      eHealth and understanding eHealth). Whilst further studies are required to
      confirm this finding, it may be necessary for these constructs of the eHEALS to
      be scored separately. The nine HLQ subscales were shown to measure a single
      construct of health literacy. However, participants' scores may not represent
      their actual level of ability, as distinction between response categories was
      unclear for the last four subscales. Reducing the response categories of these
      subscales may improve the ability of the HLQ to distinguish between different
      levels of health literacy.

PMID- 28448498
TI  - Personalized glucose forecasting for type 2 diabetes using data assimilation.
AB  - Type 2 diabetes leads to premature death and reduced quality of life for 8% of
      Americans. Nutrition management is critical to maintaining glycemic control, yet
      it is difficult to achieve due to the high individual differences in glycemic
      response to nutrition. Anticipating glycemic impact of different meals can be
      challenging not only for individuals with diabetes, but also for expert diabetes
      educators. Personalized computational models that can accurately forecast an
      impact of a given meal on an individual's blood glucose levels can serve as the
      engine for a new generation of decision support tools for individuals with
      diabetes. However, to be useful in practice, these computational engines need to
      generate accurate forecasts based on limited datasets consistent with typical
      self-monitoring practices of individuals with type 2 diabetes. This paper uses
      three forecasting machines: (i) data assimilation, a technique borrowed from
      atmospheric physics and engineering that uses Bayesian modeling to infuse data
      with human knowledge represented in a mechanistic model, to generate real-time,
      personalized, adaptable glucose forecasts; (ii) model averaging of data
      assimilation output; and (iii) dynamical Gaussian process model regression. The
      proposed data assimilation machine, the primary focus of the paper, uses a
      modified dual unscented Kalman filter to estimate states and parameters,
      personalizing the mechanistic models. Model selection is used to make a
      personalized model selection for the individual and their measurement
      characteristics. The data assimilation forecasts are empirically evaluated
      against actual postprandial glucose measurements captured by individuals with
      type 2 diabetes, and against predictions generated by experienced diabetes
      educators after reviewing a set of historical nutritional records and glucose
      measurements for the same individual. The evaluation suggests that the data
      assimilation forecasts compare well with specific glucose measurements and match
      or exceed in accuracy expert forecasts. We conclude by examining ways to present
      predictions as forecast-derived range quantities and evaluate the comparative
      advantages of these ranges.

PMID- 28448499
TI  - When do correlations increase with firing rates in recurrent networks?
AB  - A central question in neuroscience is to understand how noisy firing patterns are
      used to transmit information. Because neural spiking is noisy, spiking patterns
      are often quantified via pairwise correlations, or the probability that two cells
      will spike coincidentally, above and beyond their baseline firing rate. One
      observation frequently made in experiments, is that correlations can increase
      systematically with firing rate. Theoretical studies have determined that
      stimulus-dependent correlations that increase with firing rate can have
      beneficial effects on information coding; however, we still have an incomplete
      understanding of what circuit mechanisms do, or do not, produce this correlation
      firing rate relationship. Here, we studied the relationship between pairwise
      correlations and firing rates in recurrently coupled excitatory-inhibitory
      spiking networks with conductance-based synapses. We found that with stronger
      excitatory coupling, a positive relationship emerged between pairwise
      correlations and firing rates. To explain these findings, we used linear response
      theory to predict the full correlation matrix and to decompose correlations in
      terms of graph motifs. We then used this decomposition to explain why covariation
      of correlations with firing rate-a relationship previously explained in
      feedforward networks driven by correlated input-emerges in some recurrent
      networks but not in others. Furthermore, when correlations covary with firing
      rate, this relationship is reflected in low-rank structure in the correlation
      matrix.

PMID- 28448501
TI  - Employment 12 months after kidney transplantation: An in-depth bio-psycho-social
      analysis of the Swiss Transplant Cohort.
AB  - BACKGROUND: Return to work with or after a chronic disease is a dynamic process
      influenced by a variety of interactions between personal, work, societal and
      medical resources or constraints. The aim of this study was to identify
      predictors for employment 12 months after transplantation in kidney patients,
      applying a bio-psycho-social model. METHODS: All kidney patients followed in the
      Swiss Transplant Cohort between May 2008 and December 2012, aged 18 to 65 were
      assessed before, 6 and 12 months after transplantation. RESULTS: Of the 689
      included patients, 56.2% worked 12 months post- transplantation compared to 58.9%
      pre-transplantation. Age, education, self-perceived health (6 months post-
      transplantation), pre- transplantation employment and receiving an organ from a
      living donor are significant predictors of employment post- transplantation.
      Moreover, while self-perceived health increased post- transplantation, depression
      score decreased only among those employed 12 months post- transplantation. Pre-
      transplantation employment status was the main predictor for post-
      transplantation employment (OR = 18.6) and was associated with sex, age,
      education, depression and duration of dialysis. An organ from a living donor
      (42.1%) was more frequent in younger patients, with higher education, no diabetes
      and shorter waiting time to surgery. CONCLUSION: Transplantation did not increase
      employment in end-stage kidney disease patients but helped maintaining
      employment. Pre-transplantation employment has been confirmed to be the most
      important predictor of post-transplantation employment. Furthermore, socio
      demographic and individual factors predicted directly and indirectly the post
      transplantation employment status. With living donor, an additional predictor
      linked to social factors and the medical procedure has been identified.

PMID- 28448502
TI  - Contraceptive uptake after training community health workers in couples
      counseling: A cluster randomized trial.
AB  - BACKGROUND: Young women in Malawi face many challenges in accessing family
      planning (FP), including distance to the health facility and partner disapproval.
      Our primary objective was to assess if training HSAs in couples counseling would
      increase modern FP uptake among young women. METHODS: In this cluster randomized
      controlled trial, 30 HSAs from Lilongwe, Malawi received training in FP. The HSAs
      were then randomized 1:1 to receive or not receive additional training in couples
      counseling. All HSAs were asked to provide FP counseling to women in their
      communities and record their contraceptive uptake over 6 months. Sexually-active
      women <30 years of age who had never used a modern FP method were included in
      this analysis. Generalized estimating equations with an exchangeable correlation
      matrix to account for clustering by HSA were used to estimate risk differences
      (RDs) and 95% confidence intervals (CIs). RESULTS: 430 (53%) young women were
      counseled by the 15 HSAs who received couples counseling training, and 378 (47%)
      were counseled by the 15 HSAs who did not. 115 (26%) from the couples counseling
      group had male partners present during their first visit, compared to only 6 (2%)
      from the other group (RD: 0.21, 95% CI: 0.09 to 0.33, p<0.01). Nearly all (99.5%)
      initiated a modern FP method, with no difference between groups (p = 0.09). Women
      in the couples counseling group were 8% more likely to receive male condoms (RD:
      0.08, 95% CI: -7% to 23%, p = 0.28) and 8% more likely to receive dual methods
      (RD: 0.08, 95% CI: -0.065, 0.232, p = 0.274). CONCLUSION: Training HSAs in FP led
      to high modern FP uptake among young women who had never used FP. Couples
      counseling training increased male involvement with a trend towards higher male
      condom uptake.

PMID- 28448503
TI  - Etiologic effects and optimal intakes of foods and nutrients for risk of
      cardiovascular diseases and diabetes: Systematic reviews and meta-analyses from
      the Nutrition and Chronic Diseases Expert Group (NutriCoDE).
AB  - BACKGROUND: Dietary habits are major contributors to coronary heart disease,
      stroke, and diabetes. However, comprehensive evaluation of etiologic effects of
      dietary factors on cardiometabolic outcomes, their quantitative effects, and
      corresponding optimal intakes are not well-established. OBJECTIVE: To
      systematically review the evidence for effects of dietary factors on
      cardiometabolic diseases, including comprehensively assess evidence for
      causality; estimate magnitudes of etiologic effects; evaluate heterogeneity and
      potential for bias in these etiologic effects; and determine optimal population
      intake levels. METHODS: We utilized Bradford-Hill criteria to assess probable or
      convincing evidence for causal effects of multiple diet-cardiometabolic disease
      relationships. Etiologic effects were quantified from published or de novo meta
      analyses of prospective studies or randomized clinical trials, incorporating
      standardized units, dose-response estimates, and heterogeneity by age and other
      characteristics. Potential for bias was assessed in validity analyses. Optimal
      intakes were determined by levels associated with lowest disease risk. RESULTS:
      We identified 10 foods and 7 nutrients with evidence for causal cardiometabolic
      effects, including protective effects of fruits, vegetables, beans/legumes,
      nuts/seeds, whole grains, fish, yogurt, fiber, seafood omega-3s, polyunsaturated
      fats, and potassium; and harms of unprocessed red meats, processed meats, sugar
      sweetened beverages, glycemic load, trans-fats, and sodium. Proportional
      etiologic effects declined with age, but did not generally vary by sex.
      Established optimal population intakes were generally consistent with observed
      national intakes and major dietary guidelines. In validity analyses, the
      identified effects of individual dietary components were similar to quantified
      effects of dietary patterns on cardiovascular risk factors and hard endpoints.
      CONCLUSIONS: These novel findings provide a comprehensive summary of causal
      evidence, quantitative etiologic effects, heterogeneity, and optimal intakes of
      major dietary factors for cardiometabolic diseases, informing disease impact
      estimation and policy planning and priorities.

PMID- 28448504
TI  - Impaired sense of agency in functional movement disorders: An fMRI study.
AB  - The sense of agency (SA) is an established framework that refers to our ability
      to exert and perceive control over our own actions. Having an intact SA provides
      the basis for the human perception of voluntariness, while impairments in SA are
      hypothesized to lead to the perception of movements being involuntary that may be
      seen many neurological or psychiatric disorders. Individuals with functional
      movement disorders (FMD) experience a lack of control over their movements, yet
      these movements appear voluntary by physiology. We used fMRI to explore whether
      alterations in SA in an FMD population could explain why these patients feel
      their movements are involuntary. We compared the FMD group to a control group
      that was previously collected using an ecologically valid, virtual-reality
      movement paradigm that could modulate SA. We found selective dysfunction of the
      SA neural network, whereby the dorsolateral prefrontal cortex and pre
      supplementary motor area on the right did not respond differentially to the loss
      of movement control. These findings provide some of the strongest evidence to
      date for a physiological basis underlying these disabling disorders.

PMID- 28448505
TI  - Polyphenolic extract of InsP 5-ptase expressing tomato plants reduce the
      proliferation of MCF-7 breast cancer cells.
AB  - In recent years, by extensive achievements in understanding the mechanisms and
      the pathways affected by cancer, the focus of cancer research is shifting from
      developing new chemotherapy methods to using natural compounds with therapeutic
      properties to reduce the adverse effects of synthetic drugs on human health. We
      used fruit extracts from previously generated human type I InsP 5-ptase gene
      expressing transgenic tomato plants for assessment of the anti-cancer activity of
      established genetically modified tomato lines. Cellular assays (MTT, Fluorescent
      microscopy, Flow Cytometry analysis) were used to confirm that InsP 5-ptase fruit
      extract was more effective for reducing the proliferation of breast cancer cells
      compared to wild-type tomato fruit extract. Metabolome analysis of InsP 5-ptase
      expressing tomato fruits performed by LC-MS identified tomato metabolites that
      may play a key role in the increased anti-cancer activity observed for the
      transgenic fruits. Total transcriptome analysis of cancer cells (MCF-7 line)
      exposed to an extract of transgenic fruits revealed a number of differently
      regulated genes in the cells treated with transgenic extract compared to
      untreated cells or cells treated with wild-type tomato extract. Together, this
      data demonstrate the potential role of the plant derived metabolites in
      suppressing cell viability of cancer cells and further prove the potential
      application of plant genetic engineering in the cancer research and drug
      discovery.

PMID- 28448506
TI  - The dynamics of behavior in modified dictator games.
AB  - We investigate the dynamics of individual pro-social behavior over time. The
      dynamics are tested by running the same experiment with the same subjects at
      several points in time. To exclude learning and reputation building, we employ
      non-strategic decision tasks and a sequential prisoners-dilemma as a control
      treatment. In the first wave, pro-social concerns explain a high share of
      individual decisions. Pro-social decisions decrease over time, however. In the
      final wave, most decisions can be accounted for by assuming pure selfishness.
      Stable behavior in the sense that subjects stick to their decisions over time is
      observed predominantly for purely selfish subjects. We offer two explanation for
      our results: diminishing experimenter demand effects and moral self-licensing.

PMID- 28448507
TI  - Detecting the impact of temperature on transmission of Zika, dengue, and
      chikungunya using mechanistic models.
AB  - Recent epidemics of Zika, dengue, and chikungunya have heightened the need to
      understand the seasonal and geographic range of transmission by Aedes aegypti and
      Ae. albopictus mosquitoes. We use mechanistic transmission models to derive
      predictions for how the probability and magnitude of transmission for Zika,
      chikungunya, and dengue change with mean temperature, and we show that these
      predictions are well matched by human case data. Across all three viruses, models
      and human case data both show that transmission occurs between 18-34 degrees C
      with maximal transmission occurring in a range from 26-29 degrees C. Controlling
      for population size and two socioeconomic factors, temperature-dependent
      transmission based on our mechanistic model is an important predictor of human
      transmission occurrence and incidence. Risk maps indicate that tropical and
      subtropical regions are suitable for extended seasonal or year-round
      transmission, but transmission in temperate areas is limited to at most three
      months per year even if vectors are present. Such brief transmission windows
      limit the likelihood of major epidemics following disease introduction in
      temperate zones.

PMID- 28448508
TI  - A longitudinal cline characterizes the genetic structure of human populations in
      the Tibetan plateau.
AB  - Indigenous populations of the Tibetan plateau have attracted much attention for
      their good performance at extreme high altitude. Most genetic studies of Tibetan
      adaptations have used genetic variation data at the genome scale, while genetic
      inferences about their demography and population structure are largely based on
      uniparental markers. To provide genome-wide information on population structure,
      we analyzed new and published data of 338 individuals from indigenous populations
      across the plateau in conjunction with worldwide genetic variation data. We found
      a clear signal of genetic stratification across the east-west axis within Tibetan
      samples. Samples from more eastern locations tend to have higher genetic affinity
      with lowland East Asians, which can be explained by more gene flow from lowland
      East Asia onto the plateau. Our findings corroborate a previous report of
      admixture signals in Tibetans, which were based on a subset of the samples
      analyzed here, but add evidence for isolation by distance in a broader geospatial
      context.

PMID- 28448509
TI  - Better than counting seconds: Identifying fallers among healthy elderly using
      fusion of accelerometer features and dual-task Timed Up and Go.
AB  - Devices and sensors for identification of fallers can be used to implement
      actions to prevent falls and to allow the elderly to live an independent life
      while reducing the long-term care costs. In this study we aimed to investigate
      the accuracy of Timed Up and Go test, for fallers' identification, using fusion
      of features extracted from accelerometer data. Single and dual tasks TUG (manual
      and cognitive) were performed by a final sample (94% power) of 36 community
      dwelling healthy older persons (18 fallers paired with 18 non-fallers) while they
      wear a single triaxial accelerometer at waist with sampling rate of 200Hz. The
      segmentation of the TUG different trials and its comparative analysis allows to
      better discriminate fallers from non-fallers, while conventional functional tests
      fail to do so. In addition, we show that the fusion of features improve the
      discrimination power, achieving AUC of 0.84 (Sensitivity = Specificity = 0.83,
      95% CI 0.62-0.91), and demonstrating the clinical relevance of the study. We
      concluded that features extracted from segmented TUG trials acquired with dual
      tasks has potential to improve performance when identifying fallers via
      accelerometer sensors, which can improve TUG accuracy for clinical and
      epidemiological applications.

PMID- 28448510
TI  - Manure and tillage use in remediation of eroded land and impacts on soil chemical
      properties.
AB  - Soil loss through wind and water erosion is an ongoing problem in semiarid
      regions. A thin layer of top soil loss over a hectare of cropland could be
      corresponding to tons of productive soil loss per hectare. The objectives of this
      study were to evaluate the influence of beef feedlot manure, tillage and legume
      grass mixtures on changes in soil quality and nutrient components. The study was
      initiated in 2006 on an eroded site near Akron, Colorado, on a Norka-Colby very
      fine sandy loam (fine-silty, mixed, mesic, Aridic, Argiustolls). Tillage
      treatments were no-tillage, shallow tillage (sweeps operations with V-blade) and
      deep tillage (DT; moldboard plow operations). In one set of plots, DT was
      implemented biannually (DT-2); and in another set the DT was done once at the
      initiation of the experiment in 2006. Amendments consisted of beef manure and
      urea (46-0-0), N fertilizer. Both amendments were added at low and high rates. A
      control treatment, with no fertilizer or manure added, was included with no
      tillage and shallow tillage only. Six years of manure addition and tillage
      significantly altered soil chemical properties compared with fertilizer and grass
      legume mixtures. Across all the tillage treatments, at the 0-30 cm depth, soil pH
      from 2006 to 2012, was reduced 1.8 fold with high-manure compared with high
      fertilizer treatment. Soil EC, Na, and SAR increased by 2.7 fold while soil P
      increase by 3.5 fold with high-manure treatment compared with low-manure from
      2006 to 2012 across all the tillage treatments at the surface 0-30 cm. Soil
      organic carbon associated with high-manure was 71% higher than low-manure and
      230% higher than high-fertilizer treatments in the 0-60 cm depth. Similar
      patterns were observed with soil total N. Overall, manure amendments greatly
      improved the soil nutrient status on this eroded site. However, the legume grass
      mixtures showed little effect on improving soils chemical properties. The
      micronutrients supplied by manure improved the soil nutrient status compared with
      inorganic fertilizer, the grass, and the grass-legume treatments. We concluded
      that more than six years are needed to measure significant improvements in soil
      quality from specific treatments, specifically fertilizer, grasses, and grass
      legume mixtures in such eroded crop land.

PMID- 28448511
TI  - Tracking disease progression by searching paths in a temporal network of
      biological processes.
AB  - Metabolic disorders such as obesity and diabetes are diseases which develop
      gradually over time through the perturbations of biological processes. These
      perturbed biological processes usually work in an interdependent way. Systematic
      experiments tracking disease progression at gene level are usually conducted
      through a temporal microarray data. There is a need for developing methods to
      analyze such highly complex data to capture disease progression at the molecular
      level. In the present study, we have considered temporal microarray data from an
      experiment conducted to study development of obesity and diabetes in mice. We
      first constructed a network between biological processes through common genes. We
      analyzed the data to obtain perturbed biological processes at each time point.
      Finally, we used the biological process network to find links between these
      perturbed biological processes. This enabled us to identify paths linking initial
      perturbed processes with final perturbed processes which capture disease
      progression. Using different datasets and statistical tests, we established that
      these paths are highly precise to the dataset from which these are obtained. We
      also established that the connecting genes present in these paths might contain
      some biological information and thus can be used for further mechanistic studies.
      The methods developed in our study are also applicable to a broad array of
      temporal data.

PMID- 28448512
TI  - Suppression of the Escherichia coli dnaA46 mutation by changes in the activities
      of the pyruvate-acetate node links DNA replication regulation to central carbon
      metabolism.
AB  - To ensure faithful transmission of genetic material to progeny cells, DNA
      replication is tightly regulated, mainly at the initiation step. Escherichia coli
      cells regulate the frequency of initiation according to growth conditions.
      Results of the classical, as well as the latest studies, suggest that the DNA
      replication in E. coli starts at a predefined, constant cell volume per
      chromosome but the mechanisms coordinating DNA replication with cell growth are
      still not fully understood. Results of recent investigations have revealed a role
      of metabolic pathway proteins in the control of cell division and a direct link
      between metabolism and DNA replication has also been suggested both in Bacillus
      subtilis and E. coli cells. In this work we show that defects in the acetate
      overflow pathway suppress the temperature-sensitivity of a defective replication
      initiator-DnaA under acetogenic growth conditions. Transcriptomic and metabolic
      analyses imply that this suppression is correlated with pyruvate accumulation,
      resulting from alterations in the pyruvate dehydrogenase (PDH) activity.
      Consequently, deletion of genes encoding the pyruvate dehydrogenase subunits
      likewise resulted in suppression of the thermal-sensitive growth of the dnaA46
      strain. We propose that the suppressor effect may be directly related to the PDH
      complex activity, providing a link between an enzyme of the central carbon
      metabolism and DNA replication.

PMID- 28448500
TI  - Genome-wide physical activity interactions in adiposity - A meta-analysis of
      200,452 adults.
AB  - Physical activity (PA) may modify the genetic effects that give rise to increased
      risk of obesity. To identify adiposity loci whose effects are modified by PA, we
      performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist
      circumference and waist-hip ratio from up to 200,452 adults of European (n =
      180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it
      into a dichotomous variable where, on average, 23% of participants were
      categorized as inactive and 77% as physically active. While we replicate the
      interaction with PA for the strongest known obesity-risk locus in the FTO gene,
      of which the effect is attenuated by ~30% in physically active individuals
      compared to inactive individuals, we do not identify additional loci that are
      sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and
      interaction with PA, we identify 11 novel adiposity loci, suggesting that
      accounting for PA or other environmental factors that contribute to variation in
      adiposity may facilitate gene discovery.

PMID- 28448513
TI  - Outdoor activity and myopia progression in 4-year follow-up of Chinese primary
      school children: The Beijing Children Eye Study.
AB  - PURPOSE: To investigate factors associated with ocular axial elongation and
      myopia progression during a 4-year follow-up in primary school children in
      Beijing. METHODS: This school-based study included 382 grade-1 children at
      baseline in 2011 (age:6.3+/-0.4 years) with 305 (79.8%) returning for the follow
      up examination in 2015. At baseline and in yearly follow-up examinations, the
      children underwent a comprehensive eye examination including auto-refractometry,
      ocular biometry with measurement of axial length, and fundus photography. The
      parents underwent a standardized interview. RESULTS: During the study period, the
      mean axial length elongated by 1.15+/-0.56mm in boys and 1.10+/-0.63mm in girls.
      At baseline and at the end of follow-up, axial length was significantly (P<0.001)
      longer in boys, with no difference (P = 0.50) between genders in axial
      elongation. In multivariate analysis, greater axial elongation was associated
      (regression coefficient r2:0.15) with less time spent outdoors (P = 0.004;
      standardized coefficient beta: -0.22), more time spent indoors with studying (P =
      0.02; beta: 0.18) and paternal myopia (P = 0.03; beta: 0.16). Larger increases in
      the axial length/anterior corneal curvature (AL/CC) ratio were associated
      (r2:0.09) with less time spent outdoors (PP = 0.003; beta: -0.22) and maternal
      myopia (PP = 0.02; beta: 0.18). CONCLUSIONS: Myopic axial elongation during a 4
      year follow-up was associated with shorter time spent outdoors and longer time
      spent indoors studying and with parental myopia. Other factors such as level of
      paternal education, family income, gender and region of habitation were
      significantly associated with axial elongation and with myopia progression only
      in univariate analysis.

PMID- 28448514
TI  - A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic
      astrocytoma.
AB  - Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent
      feature of PA is deregulation of the mitogen activated protein kinase (MAPK)
      pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1
      gene fusions and point mutations (e.g. BRAFV600E). These features may serve as
      diagnostic and prognostic markers, and also facilitate development of targeted
      therapy. The aims of this study were to characterize the genetic alterations
      underlying the development of PA in six tumor cases, and evaluate methods for
      fusion oncogene detection. Using a combined analysis of RNA sequencing and copy
      number variation data we identified a new BRAF fusion involving the 5' gene
      fusion partner GTF2I (7q11.23), not previously described in PA. The new GTF2I
      BRAF 19-10 fusion was found in one case, while the other five cases harbored the
      frequent KIAA1549-BRAF 16-9 fusion gene. Similar to other BRAF fusions, the GTF2I
      BRAF fusion retains an intact BRAF kinase domain while the inhibitory N-terminal
      domain is lost. Functional studies on GTF2I-BRAF showed elevated MAPK pathway
      activation compared to BRAFWT. Comparing fusion detection methods, we found
      Fluorescence in situ hybridization with BRAF break apart probe as the most
      sensitive method for detection of different BRAF rearrangements (GTF2I-BRAF and
      KIAA1549-BRAF). Our finding of a new BRAF fusion in PA further emphasis the
      important role of B-Raf in tumorigenesis of these tumor types. Moreover, the
      consistency and growing list of BRAF/RAF gene fusions suggests these
      rearrangements to be informative tumor markers in molecular diagnostics, which
      could guide future treatment strategies.

PMID- 28448515
TI  - Chronic cocaine induces HIF-VEGF pathway activation along with angiogenesis in
      the brain.
AB  - Cocaine induces vasoconstriction in cerebral vessels, which with repeated use can
      result in transient ischemic attacks and cerebral strokes. However, the
      neuroadaptations that follow cocaine's vasoconstricting effects are not well
      understood. Here, we investigated the effects of chronic cocaine exposure (2 and
      4 weeks) on markers of vascular function and morphology in the rat brain. For
      this purpose we measured nitric oxide (NO) concentration in plasma, brain
      neuronal nitric oxide synthase (nNOS or NOS1), HIF-1alpha, and VEGF expression in
      different brain regions, i.e., middle prefrontal cortex, somatosensory cortex,
      nucleus accumbens, and dorsal striatum, using ELISA or Western blot.
      Additionally, microvascular density in these brain regions was measured using
      immunofluorescence microscopy. We showed that chronic cocaine significantly
      affected NOS1, HIF-1alpha and VEGF expression, in a region- and cocaine treatment
      time- dependent manner. Cerebral microvascular density increased significantly in
      parallel to these neurochemical changes. Furthermore, significant correlations
      were detected between VEGF expression and microvascular density in cortical
      regions (middle prefrontal cortex and somatosensory cortex), but not in striatal
      regions (nucleus accumbens and dorsal striatum). These results suggest that
      following chronic cocaine use, as cerebral ischemia developed, NOS1, the
      regulatory protein to counteract blood vessel constriction, was upregulated;
      meanwhile, the HIF-VEGF pathway was activated to increase microvascular density
      (i.e., angiogenesis) and thus restore local blood flow and oxygen supply. These
      physiological responses were triggered presumably as an adaptation to minimize
      ischemic injury caused by cocaine. Therefore, effectively promoting such
      physiological responses may provide novel and effective therapeutic solutions to
      treat cocaine-induced cerebral ischemia and stroke.

PMID- 28448516
TI  - Natural variation of piRNA expression affects immunity to transposable elements.
AB  - In the Drosophila germline, transposable elements (TEs) are silenced by PIWI
      interacting RNA (piRNA) that originate from distinct genomic regions termed piRNA
      clusters and are processed by PIWI-subfamily Argonaute proteins. Here, we explore
      the variation in the ability to restrain an alien TE in different Drosophila
      strains. The I-element is a retrotransposon involved in the phenomenon of I-R
      hybrid dysgenesis in Drosophila melanogaster. Genomes of R strains do not contain
      active I-elements, but harbour remnants of ancestral I-related elements. The
      permissivity to I-element activity of R females, called reactivity, varies
      considerably in natural R populations, indicating the existence of a strong
      natural polymorphism in defense systems targeting transposons. To reveal the
      nature of such polymorphisms, we compared ovarian small RNAs between R strains
      with low and high reactivity and show that reactivity negatively correlates with
      the ancestral I-element-specific piRNA content. Analysis of piRNA clusters
      containing remnants of I-elements shows increased expression of the piRNA
      precursors and enrichment by the Heterochromatin Protein 1 homolog, Rhino, in
      weak R strains, which is in accordance with stronger piRNA expression by these
      regions. To explore the nature of the differences in piRNA production, we focused
      on two R strains, weak and strong, and showed that the efficiency of maternal
      inheritance of piRNAs as well as the I-element copy number are very similar in
      both strains. At the same time, germline and somatic uni-strand piRNA clusters
      generate more piRNAs in strains with low reactivity, suggesting the relationship
      between the efficiency of primary piRNA production and variable response to TE
      invasions. The strength of adaptive genome defense is likely driven by naturally
      occurring polymorphisms in the rapidly evolving piRNA pathway proteins. We
      hypothesize that hyper-efficient piRNA production is contributing to elimination
      of a telomeric retrotransposon HeT-A, which we have observed in one particular
      transposon-resistant R strain.

PMID- 28448517
TI  - Cryptic chytridiomycosis linked to climate and genetic variation in amphibian
      populations of the southeastern United States.
AB  - North American amphibians have recently been impacted by two major emerging
      pathogens, the fungus Batrachochytrium dendrobatidis (Bd) and iridoviruses in the
      genus Ranavirus (Rv). Environmental factors and host genetics may play important
      roles in disease dynamics, but few studies incorporate both of these components
      into their analyses. Here, we investigated the role of environmental and genetic
      factors in driving Bd and Rv infection prevalence and severity in a biodiversity
      hot spot, the southeastern United States. We used quantitative PCR to
      characterize Bd and Rv dynamics in natural populations of three amphibian
      species: Notophthalmus perstriatus, Hyla squirella and Pseudacris ornata. We
      combined pathogen data, genetic diversity metrics generated from neutral markers,
      and environmental variables into general linear models to evaluate how these
      factors impact infectious disease dynamics. Occurrence, prevalence and intensity
      of Bd and Rv varied across species and populations, but only one species,
      Pseudacris ornata, harbored high Bd intensities in the majority of sampled
      populations. Genetic diversity and climate variables both predicted Bd
      prevalence, whereas climatic variables alone predicted infection intensity. We
      conclude that Bd is more abundant in the southeastern United States than
      previously thought and that genetic and environmental factors are both important
      for predicting amphibian pathogen dynamics. Incorporating both genetic and
      environmental information into conservation plans for amphibians is necessary for
      the development of more effective management strategies to mitigate the impact of
      emerging infectious diseases.

PMID- 28448518
TI  - Clinical efficacy and safety of mesenchymal stem cell transplantation for
      osteoarthritis treatment: A meta-analysis.
AB  - PURPOSE: The aim of this study was to evaluate the therapeutic efficacy and
      safety of mesenchymal stem cells (MSCs) for the treatment of patients with knee
      osteoarthritis (OA). MATERIALS: We performed a meta-analysis of relevant
      published clinical studies. An electronic search was conducted for randomized
      controlled trials (RCTs) of MSC-based therapy in knee OA. The visual analogue
      scale (VAS), International Knee Documentation Committee (IKDC) form, Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne
      algofunctional indices (Lequesne), Lysholm knee scale (Lysholm), Tegner activity
      scale (Tegner) and adverse events (AEs) were evaluated. RESULTS: Eleven eligible
      trials with 582 knee OA patients were included in the present meta-analysis. We
      demonstrated that MSC treatment could significantly decrease VAS and increase
      IKDC scoresafter a 24-month follow-up compared with controls (P<0.05). MSC
      therapy also showed significant decreases in WOMAC and Lequesne scores after the
      12-month follow-up (P<0.01). Analysis of Lysholm (24-month) and Tegner (12- and
      24-month) scores also demonstrated favorable results for MSC treatment (P<0.05).
      CONCLUSION: Overall, MSC transplantation treatment was shown to be safe and has
      great potential as an efficacious clinical therapy for patients with knee OA.

PMID- 28448519
TI  - Zika infection of neural progenitor cells perturbs transcription in
      neurodevelopmental pathways.
AB  - BACKGROUND: A recent study of the gene expression patterns of Zika virus (ZIKV)
      infected human neural progenitor cells (hNPCs) revealed transcriptional
      dysregulation and identified cell cycle-related pathways that are affected by
      infection. However deeper exploration of the information present in the RNA-Seq
      data can be used to further elucidate the manner in which Zika infection of hNPCs
      affects the transcriptome, refining pathway predictions and revealing isoform
      specific dynamics. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data published by
      Tang et al. using state-of-the-art tools for transcriptome analysis. By
      accounting for the experimental design and estimation of technical and
      inferential variance we were able to pinpoint Zika infection affected pathways
      that highlight Zika's neural tropism. The examination of differential genes
      reveals cases of isoform divergence. CONCLUSIONS: Transcriptome analysis of Zika
      infected hNPCs has the potential to identify the molecular signatures of Zika
      infected neural cells. These signatures may be useful for diagnostics and for the
      resolution of infection pathways that can be used to harvest specific targets for
      further study.

PMID- 28448520
TI  - Association between vitamin D deficiency and health-related quality of life in
      patients with chronic kidney disease from the KNOW-CKD study.
AB  - Vitamin D deficiency is a growing health problem in both the general population
      and in patients with chronic kidney disease (CKD). However, the relationship
      between serum 25-hydroxyvitamin D levels and health-related quality of life in
      CKD is not well established. This study examined the association between vitamin
      D deficiency and quality of life in pre-dialysis CKD patients. Serum 25
      hydroxyvitamin D levels and the Korean version of the Kidney Disease Quality of
      Life short form were obtained for 1844 pre-dialysis CKD patients in the
      prospective KoreaN cohort Study for Outcomes in patients With Chronic Kidney
      Disease (KNOW-CKD). The baseline estimated glomerular filtration rate was 50.26
      +/- 0.71 mL/min/1.73 m2. We identified 1294 (70.2%) patients with vitamin D
      deficiency, defined as a 25-hydroxyvitamin D level < 20 ng/ml. The scores of the
      kidney disease component summary, physical component summary, and mental
      component summary in the vitamin D deficiency group were significantly lower
      compared to the scores of those without vitamin D deficiency. The serum 25
      hydroxyvitamin D level was independently associated with the kidney disease
      component summary and mental component summary scores (beta = 0.147, p = 0.003
      and beta = 0.151, p = 0.047). In conclusion, there was a significant association
      between serum 25-hydroxyvitamin D levels and kidney disease component summary and
      mental component summary scores in pre-dialysis CKD patients.

PMID- 28448521
TI  - Immunization with Toxoplasma gondii peroxiredoxin 1 induces protective immunity
      against toxoplasmosis in mice.
AB  - To develop a vaccine against Toxoplasma gondii, a vaccine antigen with immune
      stimulating activity is required. In the present study, we investigated the
      immunogenicity and prophylactic potential of T. gondii peroxiredoxin 1 (TgPrx1).
      The TgPrx1 was detected in the ascitic fluid of mice 6 days postinfection, while
      specific antibody levels were low in the sera of chronically infected mice.
      Treatment of murine peritoneal macrophages with recombinant TgPrx1 triggered IL
      12p40 and IL-6 production, but not IL-10 production. In response to TgPrx1,
      activation of NF-kB and IL-6 production were confirmed in mouse macrophage cell
      line (RAW 264.7). These results suggest the immune-stimulating potentials of
      TgPrx1. Immunization of mice with recombinant TgPrx1 stimulated specific antibody
      production (IgG1 and IgG2c). Moreover, spleen cell proliferation and interferon
      gamma production significantly increased in the TgPrx1- sensitized cells from
      mice immunized with the same antigen. Immunization with TgPrx1 also increased
      mouse survival and decreased cerebral parasite burden against lethal T. gondii
      infection. Thus, our results suggest that TgPrx1 efficiently induces humoral and
      cellular immune responses and is useful as a new vaccine antigen against
      toxoplasmosis.

PMID- 28448522
TI  - Nestin expression is upregulated in the fibrotic rat heart and is localized in
      collagen-expressing mesenchymal cells and interstitial CD31(+)- cells.
AB  - Renal and lung fibrosis was characterized by the accumulation of collagen
      immunoreactive mesenchymal cells expressing the intermediate filament protein
      nestin. The present study tested the hypothesis that nestin expression was
      increased in the hypertrophied/fibrotic left ventricle of suprarenal abdominal
      aorta constricted adult male Sprague-Dawley rats and induced in ventricular
      fibroblasts by pro-fibrotic peptide growth factors. Nestin protein levels were
      upregulated in the pressure-overloaded left ventricle and expression positively
      correlated with the rise of mean arterial pressure. In sham and pressure
      overloaded hearts, nestin immunoreactivity was detected in collagen type I(+)-and
      CD31(+)-cells identified in the interstitium and perivascular region whereas
      staining was absent in smooth muscle alpha-actin(+)-cells. A significantly
      greater number of collagen type I(+)-cells co-expressing nestin was identified in
      the left ventricle of pressure-overloaded rats. Moreover, an accumulation of
      nestin(+)-cells lacking collagen, CD31 and smooth muscle alpha-actin staining was
      selectively observed at the adventitial region of predominantly large calibre
      blood vessels in the hypertrophied/fibrotic left ventricle. Angiotensin II and
      TGF-beta1 stimulation of ventricular fibroblasts increased nestin protein levels
      via phosphatidylinositol 3-kinase- and protein kinase C/SMAD3-dependent pathways,
      respectively. CD31/eNOS(+)-rat cardiac microvascular endothelial cells
      synthesized/secreted collagen type I, expressed prolyl 4-hydroxylase and TGF
      beta1 induced nestin expression. The selective accumulation of adventitial
      nestin(+)-cells highlighted a novel feature of large vessel remodelling in the
      pressure-overloaded heart and increased appearance of collagen type I/nestin(+)
      cells may reflect an activated phenotype of ventricular fibroblasts.
      CD31/collagen/nestin(+)-interstitial cells could represent displaced endothelial
      cells displaying an unmasked mesenchymal phenotype, albeit contribution to the
      reactive fibrotic response of the pressure-overloaded heart remains unknown.

PMID- 28448524
TI  - Modelling the vertical distribution of canopy fuel load using national forest
      inventory and low-density airbone laser scanning data.
AB  - The fuel complex variables canopy bulk density and canopy base height are often
      used to predict crown fire initiation and spread. Direct measurement of these
      variables is impractical, and they are usually estimated indirectly by modelling.
      Recent advances in predicting crown fire behaviour require accurate estimates of
      the complete vertical distribution of canopy fuels. The objectives of the present
      study were to model the vertical profile of available canopy fuel in pine stands
      by using data from the Spanish national forest inventory plus low-density
      airborne laser scanning (ALS) metrics. In a first step, the vertical distribution
      of the canopy fuel load was modelled using the Weibull probability density
      function. In a second step, two different systems of models were fitted to
      estimate the canopy variables defining the vertical distributions; the first
      system related these variables to stand variables obtained in a field inventory,
      and the second system related the canopy variables to airborne laser scanning
      metrics. The models of each system were fitted simultaneously to compensate the
      effects of the inherent cross-model correlation between the canopy variables.
      Heteroscedasticity was also analyzed, but no correction in the fitting process
      was necessary. The estimated canopy fuel load profiles from field variables
      explained 84% and 86% of the variation in canopy fuel load for maritime pine and
      radiata pine respectively; whereas the estimated canopy fuel load profiles from
      ALS metrics explained 52% and 49% of the variation for the same species. The
      proposed models can be used to assess the effectiveness of different forest
      management alternatives for reducing crown fire hazard.

PMID- 28448523
TI  - Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis
      targeting into select antennal lobe regions.
AB  - Elucidating how appropriate neurite patterns are generated in neurons of the
      olfactory system is crucial for comprehending the construction of the olfactory
      map. In the Drosophila olfactory system, projection neurons (PNs), primarily
      derived from four neural stem cells (called neuroblasts), populate their cell
      bodies surrounding to and distribute their dendrites in distinct but overlapping
      patterns within the primary olfactory center of the brain, the antennal lobe
      (AL). However, it remains unclear whether the same molecular mechanisms are
      employed to generate the appropriate dendritic patterns in discrete AL glomeruli
      among PNs produced from different neuroblasts. Here, by examining a previously
      explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to
      globally control initial PN dendritic targeting along the dorsolateral-to
      ventromedial axis of the AL, we discover a new role for Sema-1a in preventing
      dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion
      into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis
      targeting phenotype seems to associate with the origins of PNs from which they
      are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis
      projection from a select AL region into adjacent glomeruli, strengthening the
      idea that Sema-1a plays an essential role in preventing abnormal dendritic
      accumulation in select AL regions. Taken together, these results demonstrate that
      Sema-1a repulsion keeps dendrites of different types of PNs away from each other,
      enabling the same types of PN dendrites to be sorted into destined AL glomeruli
      and permitting for functional assembly of olfactory circuitry.

PMID- 28448525
TI  - Brorin is required for neurogenesis, gliogenesis, and commissural axon guidance
      in the zebrafish forebrain.
AB  - Bmps regulate numerous neural functions with their regulators. We previously
      identified Brorin, a neural-specific secreted antagonist of Bmp signaling, in
      humans, mice, and zebrafish. Mouse Brorin has two cysteine-rich domains
      containing 10 cysteine residues in its core region, and these are located in
      similar positions to those in the cysteine-rich domains of Chordin family
      members, which are secreted Bmp antagonists. Zebrafish Brorin had two cysteine
      rich domains with high similarity to those of mouse Brorin. We herein examined
      zebrafish brorin in order to elucidate its in vivo actions. Zebrafish brorin was
      predominantly expressed in developing neural tissues. The overexpression of
      brorin led to the inactivation of Bmp signaling. On the other hand, the knockdown
      of brorin resulted in the activation of Bmp signaling and brorin morphants
      exhibited defective development of the ventral domain in the forebrain.
      Furthermore, the knockdown of brorin inhibited the generation of gamma
      aminobutyric acid (GABA)ergic interneurons and oligodendrocytes and promoted the
      generation of astrocytes in the forebrain. In addition, brorin was required for
      axon guidance in the forebrain. The present results suggest that Brorin is a
      secreted Bmp antagonist predominantly expressed in developing neural tissues and
      that it plays multiple roles in the development of the zebrafish forebrain.

PMID- 28448526
TI  - Human alkaline phosphatase dephosphorylates microbial products and is elevated in
      preterm neonates with a history of late-onset sepsis.
AB  - BACKGROUND: A host defense function for Alkaline phosphatases (ALPs) is suggested
      by the contribution of intestinal ALP to detoxifying bacterial lipopolysaccharide
      (endotoxin) in animal models in vivo and the elevation of ALP activity following
      treatment of human cells with inflammatory stimuli in vitro. However the activity
      of ALP in human plasma (primarily tissue-nonspecific ALP; TNAP) on
      lipopolysaccharide and other microbial products has not been assessed, nor has
      its expression been studied in preterm newborns, a vulnerable population at high
      risk of sepsis. In this context, the aim of our study was to characterize the
      activity of TNAP on Toll-like receptor (TLR) agonists and assess the
      concentrations of plasma ALP during late-onset sepsis in preterm newborns.
      METHODS: Recombinant human TNAP was incubated with microbial products and
      phosphate release was measured by malachite green assay. Plasma ALP activity was
      measured serially in a cohort of preterm (N = 129) infants at high risk of late
      onset sepsis (LOS). RESULTS: TNAP dephosphorylates poly-inosine:cytosine (Toll
      like receptor (TLR) 3 agonist) and LPS from Klebsiella pneumoniae and Salmonella
      minnesota (TLR4 agonists). Plasma ALP significantly increased postnatally over
      the first 4 weeks of life in preterm and term newborns. Bacteremic LOS in preterm
      infants (gestational age <= 30 weeks) was associated with significantly elevated
      plasma ALP at 4 weeks postnatal age. CONCLUSIONS: TNAP, the main circulating
      isozyme of ALP, de-phosphorylates TLR agonists, demonstrates a post-natal age
      dependent increase in preterm and term plasma across the first 4 weeks of life,
      and is elevated in association with preterm LOS.

PMID- 28448527
TI  - Meat consumption is a major risk factor for hepatitis E virus infection.
AB  - BACKGROUND: The incidence of autochthonous hepatitis E virus genotype 3 (HEV gt3)
      infections in Western Europe is high. Although pigs are a major reservoir of the
      virus, the exact sources and transmission route(s) of HEV gt3 to humans remain
      unclear. METHODS: To determine the role of meat consumption at a population
      level, the seroprevalence of anti-HEV IgG antibodies was compared between Dutch
      blood donors with a vegetarian lifestyle and donors who consume meat on a daily
      basis. RESULTS: The age-weighted anti-HEV IgG seroprevalence among donors not
      eating meat was significantly lower than among meat-eating donors (12.4% vs
      20.5%, p = 0.002). For both groups the prevalence strongly increased with age and
      the difference in prevalence was apparent for all age groups. CONCLUSIONS:
      Compared with meat-eating donors, the incidence of HEV infection is significantly
      lower among donors not eating meat, indicating that meat consumption is a major
      risk factor for HEV infection.

PMID- 28448528
TI  - Minimally invasive estimation of ventricular dead space volume through use of
      Frank-Starling curves.
AB  - This paper develops a means of more easily and less invasively estimating
      ventricular dead space volume (Vd), an important, but difficult to measure
      physiological parameter. Vd represents a subject and condition dependent portion
      of measured ventricular volume that is not actively participating in ventricular
      function. It is employed in models based on the time varying elastance concept,
      which see widespread use in haemodynamic studies, and may have direct diagnostic
      use. The proposed method involves linear extrapolation of a Frank-Starling curve
      (stroke volume vs end-diastolic volume) and its end-systolic equivalent (stroke
      volume vs end-systolic volume), developed across normal clinical procedures such
      as recruitment manoeuvres, to their point of intersection with the y-axis (where
      stroke volume is 0) to determine Vd. To demonstrate the broad applicability of
      the method, it was validated across a cohort of six sedated and anaesthetised
      male Pietrain pigs, encompassing a variety of cardiac states from healthy
      baseline behaviour to circulatory failure due to septic shock induced by
      endotoxin infusion. Linear extrapolation of the curves was supported by strong
      linear correlation coefficients of R = 0.78 and R = 0.80 average for pre- and
      post- endotoxin infusion respectively, as well as good agreement between the two
      linearly extrapolated y-intercepts (Vd) for each subject (no more than 7.8%
      variation). Method validity was further supported by the physiologically
      reasonable Vd values produced, equivalent to 44.3-53.1% and 49.3-82.6% of
      baseline end-systolic volume before and after endotoxin infusion respectively.
      This method has the potential to allow Vd to be estimated without a particularly
      demanding, specialised protocol in an experimental environment. Further, due to
      the common use of both mechanical ventilation and recruitment manoeuvres in
      intensive care, this method, subject to the availability of multi-beat
      echocardiography, has the potential to allow for estimation of Vd in a clinical
      environment.

PMID- 28448529
TI  - A genome-wide analysis of the RNA-guided silencing pathway in coffee reveals
      insights into its regulatory mechanisms.
AB  - microRNAs (miRNAs) are derived from self-complementary hairpin structures, while
      small-interfering RNAs (siRNAs) are derived from double-stranded RNA (dsRNA) or
      hairpin precursors. The core mechanism of sRNA production involves DICER-like
      (DCL) in processing the smallRNAs (sRNAs) and ARGONAUTE (AGO) as effectors of
      silencing, and siRNA biogenesis also involves action of RNA-Dependent RNA
      Polymerase (RDR), Pol IV and Pol V in biogenesis. Several other proteins interact
      with the core proteins to guide sRNA biogenesis, action, and turnover. We aimed
      to unravel the components and functions of the RNA-guided silencing pathway in a
      non-model plant species of worldwide economic relevance. The sRNA-guided
      silencing complex members have been identified in the Coffea canephora genome,
      and they have been characterized at the structural, functional, and evolutionary
      levels by computational analyses. Eleven AGO proteins, nine DCL proteins (which
      include a DCL1-like protein that was not previously annotated), and eight RDR
      proteins were identified. Another 48 proteins implicated in smallRNA (sRNA)
      pathways were also identified. Furthermore, we identified 235 miRNA precursors
      and 317 mature miRNAs from 113 MIR families, and we characterized ccp-MIR156, ccp
      MIR172, and ccp-MIR390. Target prediction and gene ontology analyses of 2239
      putative targets showed that significant pathways in coffee are targeted by
      miRNAs. We provide evidence of the expansion of the loci related to sRNA
      pathways, insights into the activities of these proteins by domain and catalytic
      site analyses, and gene expression analysis. The number of MIR loci and their
      targeted pathways highlight the importance of miRNAs in coffee. We identified
      several roles of sRNAs in C. canephora, which offers substantial insight into
      better understanding the transcriptional and post-transcriptional regulation of
      this major crop.

PMID- 28448530
TI  - Response of Npt2a knockout mice to dietary calcium and phosphorus.
AB  - Mutations in the renal sodium-dependent phosphate co-transporters NPT2a and NPT2c
      have been reported in patients with renal stone disease and nephrocalcinosis, but
      the relative contribution of genotype, dietary calcium and phosphate to the
      formation of renal mineral deposits is unclear. We previously reported that renal
      calcium phosphate deposits persist and/or reappear in older Npt2a-/- mice
      supplemented with phosphate despite resolution of hypercalciuria while no
      deposits are seen in wild-type (WT) mice on the same diet. Addition of calcium to
      their diets further increased calcium phosphate deposits in Npt2a-/-, but not WT
      mice. The response of PTH to dietary phosphate of Npt2a-/- was blunted when
      compared to WT mice and the response of the urinary calcium x phosphorus product
      to the addition of calcium and phosphate to the diet of Npt2a-/- was increased.
      These finding suggests that Npt2a-/- mice respond differently to dietary
      phosphate when compared to WT mice. Further evaluation in the Npt2a-/- cohort on
      different diets suggests that urinary calcium excretion, plasma phosphate and
      FGF23 levels appear to be positively correlated to renal mineral deposit
      formation while urine phosphate levels and the urine anion gap, an indirect
      measure of ammonia excretion, appear to be inversely correlated. Our observations
      in Npt2a-/- mice, if confirmed in humans, may be relevant for the optimization of
      existing and the development of novel therapies to prevent nephrolithiasis and
      nephrocalcinosis in human carriers of NPT2a and NPT2c mutations.

PMID- 28448531
TI  - Application of the transtheoretical model to sedentary behaviors and its
      association with physical activity status.
AB  - BACKGROUND: The Transtheoretical Model (TTM) is a successful framework for
      guiding behavior change programs for several health behaviors, yet its
      application to reduce of sedentary behavior has been neglected. In addition, no
      data exist regarding the association between determinants of sedentary behaviors
      based on the TTM and physical activity behavior. The purpose of this study was to
      investigate college students' stages of motivational readiness to avoid sedentary
      behaviors and relevant psychological determinants using newly developed TTM
      questionnaires and to identify the association between current physical activity
      and sedentary behaviors based on TTM constructs. METHODS: Data were obtained from
      225 college students enrolled in health education and physical education courses.
      Participants completed a package of questionnaires including validated TTM,
      physical activity and sitting time questionnaires. Participants also wore an
      accelerometer for seven consecutive days. MANOVAs were conducted to determine
      mean differences in psychological constructs across the TTM stages, and Chi
      square tests and Spearman correlation were used to evaluate the associations
      between current physical activity and sedentary behavior. RESULTS: A majority of
      the participants were in the sedentary stages, and men and women differed in
      proportion of individuals in the stages (78.0% vs. 68.1%, respectively). The
      gender difference was also found in use of the processes of change. In general,
      the mean scores of the TTM constructs increased as the stages progressed. No
      significant associations were found between the TTM constructs for sedentary
      behavior and current physical activity levels (p>0.05). CONCLUSIONS: A high
      proportion of college students were in sedentary stages regardless of physical
      activity levels, but different distributions in men and women. Participants in
      earlier stages were less likely to utilize the TTM constructs to reduce sedentary
      behaviors than those in later stages. A lack of association between physical
      activity and the psychological determinants of sedentary behavior was found.

PMID- 28448533
TI  - Determining the optimal number and location of cutoff points with application to
      data of cervical cancer.
AB  - It is often helpful to classify biomarker values into groups of different risk
      levels to facilitate evaluation of a biological, physiological, or pathological
      state. Stratification of patients into two risk groups is commonly seen, but
      there is always need for more than two groups for fine assessment. So far, there
      are no standard methods or tools to help decide how many cutoff points are
      optimal. In this study, we developed a comprehensive package that included
      methods to determine both the optimal number and locations of cutoff points for
      both survival data and dichotomized outcome. We illustrated workflow of this
      package with data from 797 patients with cervical cancer. By analyzing several
      risk factors of cervical cancer such as tumor size, body mass index (BMI), number
      of lymph nodes involved and depth of stromal invasion, in relation to survival
      and clinical outcome such as lymph nodal metastasis and lymphovascular invasion,
      we demonstrated that the best choice for BMI and stromal invasion was two cutoff
      points and one for the others. This study provided a useful tool to facilitate
      medical decisions and the analyses on cervical cancer may also be of interest to
      gynecologists. The package can be freely downloaded.

PMID- 28448532
TI  - A selected reaction monitoring mass spectrometric assessment of biomarker
      candidates diagnosing large-cell neuroendocrine lung carcinoma by the scaling
      method using endogenous references.
AB  - Selected reaction monitoring mass spectrometry (SRM-MS) -based semi-quantitation
      was performed to assess the validity of 46 selected candidate proteins for
      specifically diagnosing large-cell neuroendocrine lung carcinoma (LCNEC) and
      differentiating it from other lung cancer subtypes. The scaling method was
      applied in this study using specific SRM peak areas (AUCs) derived from the
      endogenous reference protein that normalizes all SRM AUCs obtained for the
      candidate proteins. In a screening verification study, we found that seven out of
      the 46 candidate proteins were statistically significant for the LCNEC phenotype,
      including 4F2hc cell surface antigen heavy chain (4F2hc/CD98) (p-ANOVA <=
      0.0012), retinal dehydrogenase 1 (p-ANOVA <= 0.0029), apolipoprotein A-I (p-ANOVA
      <= 0.0004), beta-enolase (p-ANOVA <= 0.0043), creatine kinase B-type (p-ANOVA <=
      0.0070), and galectin-3-binding protein (p-ANOVA = 0.0080), and
      phosphatidylethanolamine-binding protein 1 (p-ANOVA <= 0.0012). In addition, we
      also identified candidate proteins specific to the small-cell lung carcinoma
      (SCLC) subtype. These candidates include brain acid soluble protein 1 (p-ANOVA <
      0.0001) and gamma-enolase (p-ANOVA <= 0.0013). This new relative quantitation
      based approach utilizing the scaling method can be applied to assess hundreds of
      protein candidates obtained from discovery proteomic studies as a first step of
      the verification phase in biomarker development processes.

PMID- 28448534
TI  - Intense light-elicited upregulation of miR-21 facilitates glycolysis and
      cardioprotection through Per2-dependent mechanisms.
AB  - A wide search for ischemic preconditioning (IPC) mechanisms of cardioprotection
      identified the light elicited circadian rhythm protein Period 2 (Per2) to be
      cardioprotective. Studies on cardiac metabolism found a key role for light
      elicited Per2 in mediating metabolic dependence on carbohydrate metabolism. To
      profile Per2 mediated pathways following IPC of the mouse heart, we performed a
      genome array and identified 352 abundantly expressed and well-characterized Per2
      dependent micro RNAs. One prominent result of our in silico analysis for cardiac
      Per2 dependent micro RNAs revealed a selective role for miR-21 in the regulation
      of hypoxia and metabolic pathways. Based on this Per2 dependency, we subsequently
      found a diurnal expression pattern for miR-21 with higher miR-21 expression
      levels at Zeitgeber time (ZT) 15 compared to ZT3. Gain or loss of function
      studies for miR-21 using miRNA mimics or miRNA inhibitors and a Seahorse
      Bioanalyzer uncovered a critical role of miR-21 for cellular glycolysis,
      glycolytic capacity, and glycolytic reserve. Exposing mice to intense light, a
      strategy to induce Per2, led to a robust induction of cardiac miR-21 tissue
      levels and decreased infarct sizes, which was abolished in miR-21-/- mice.
      Similarly, first translational studies in humans using intense blue light
      exposure for 5 days in healthy volunteers resulted in increased plasma miR-21
      levels which was associated with increased phosphofructokinase activity, the rate
      limiting enzyme in glycolysis. Together, we identified miR-21 as cardioprotective
      downstream target of Per2 and suggest intense light therapy as a potential
      strategy to enhance miR-21 activity and subsequent carbohydrate metabolism in
      humans.

PMID- 28448536
TI  - Lateral flow immunoassay for on-site detection of Xanthomonas arboricola pv.
      pruni in symptomatic field samples.
AB  - Xanthomonas arboricola pv. pruni is a quarantine pathogen and the causal agent of
      the bacterial spot disease of stone fruits and almond, a major threat to Prunus
      species. Rapid and specific detection methods are essential to improve disease
      management, and therefore a prototype of a lateral flow immunoassay (LFIA) was
      designed for the detection of X. arboricola pv. pruni in symptomatic field
      samples. It was developed by producing polyclonal antibodies which were then
      combined with carbon nanoparticles and assembled on nitrocellulose strips. The
      specificity of the LFIA was tested against 87 X. arboricola pv. pruni strains
      from different countries worldwide, 47 strains of other Xanthomonas species and
      14 strains representing other bacterial genera. All X. arboricola pv. pruni
      strains were detected and cross-reactions were observed only with four strains of
      X. arboricola pv. corylina, a hazelnut pathogen that does not share habitat with
      X. arboricola pv. pruni. The sensitivity of the LFIA was assessed with
      suspensions from pure cultures of three X. arboricola pv. pruni strains and with
      spiked leaf extracts prepared from four hosts inoculated with this pathogen
      (almond, apricot, Japanese plum and peach). The limit of detection observed with
      both pure cultures and spiked samples was 104 CFU ml-1. To demonstrate the
      accuracy of the test, 205 samples naturally infected with X. arboricola pv. pruni
      and 113 samples collected from healthy plants of several different Prunus species
      were analyzed with the LFIA. Results were compared with those obtained by plate
      isolation and real time PCR and a high correlation was found among techniques.
      Therefore, we propose this LFIA as a screening tool that allows a rapid and
      reliable diagnosis of X. arboricola pv. pruni in symptomatic plants.

PMID- 28448535
TI  - Alpha-1 antitrypsin supplementation improves alveolar macrophages efferocytosis
      and phagocytosis following cigarette smoke exposure.
AB  - Cigarette smoking (CS), the main risk factor for COPD (chronic obstructive
      pulmonary disease) in developed countries, decreases alveolar macrophages (AM)
      clearance of both apoptotic cells and bacterial pathogens. This global deficit of
      AM engulfment may explain why active smokers have worse outcomes of COPD
      exacerbations, episodes characterized by airway infection and inflammation that
      carry high morbidity and healthcare cost. When administered as intravenous
      supplementation, the acute phase-reactant alpha-1 antitrypsin (A1AT) reduces the
      severity of COPD exacerbations in A1AT deficient (AATD) individuals and of
      bacterial pneumonia in murine models, but the effect of A1AT on AM scavenging
      functions has not been reported. Apoptotic cell clearance (efferocytosis) was
      measured in human AM isolated from patients with COPD, in primary rat AM or
      differentiated monocytes exposed to CS ex vivo, and in AM recovered from mice
      exposed to CS. A1AT (100 MUg/mL, 16 h) significantly ameliorated efferocytosis
      (by ~50%) in AM of active smokers or AM exposed ex vivo to CS. A1AT significantly
      improved AM global engulfment, including phagocytosis, even when cells were
      simultaneously challenged with apoptotic and Fc-coated (bacteria-like) targets.
      The improved efferocytosis in A1AT-treated macrophages was associated with
      inhibition of tumor necrosis factor-alpha converting enzyme (TACE) activity,
      decreased mannose receptor shedding, and markedly increased abundance of
      efferocytosis receptors (mannose- and phosphatidyl serine receptors and the
      scavenger receptor B2) on AM plasma membrane. Directed airway A1AT treatment (via
      inhalation of a nebulized solution) restored in situ airway AM efferocytosis
      after CS exposure in mice. The amelioration of CS-exposed AM global engulfment
      may render A1AT as a potential therapy for COPD exacerbations.

PMID- 28448537
TI  - Mapping of quantitative trait loci associated with resistance to net form net
      blotch (Pyrenophora teres f. teres) in a doubled haploid Norwegian barley
      population.
AB  - Barley net blotch caused by the necrotrophic fungus Pyrenophora teres is a major
      barley disease in Norway. It can cause grain shriveling and yield losses, and
      resistance in currently grown cultivars is insufficient. In this study, a set of
      589 polymorphic SNP markers was used to map resistance loci in a population of
      109 doubled haploid lines from a cross between the closely related Norwegian
      cultivars Arve (moderately susceptible) and Lavrans (moderately resistant).
      Resistance to three net form net blotch (P. teres f. teres) single spore isolates
      was evaluated at the seedling stage in the greenhouse and at the adult plant
      stage under field conditions during three years. Days to heading and plant height
      were scored to assess their influence on disease severity. At the seedling stage,
      three to four quantitative trait loci (QTL) associated with resistance were found
      per isolate used. A major, putatively novel QTL was identified on chromosome 5H,
      accounting for 23-48% of the genetic variation. Additional QTL explaining between
      12 and 16.5% were found on chromosomes 4H, 5H, 6H and 7H, with the one on 6H
      being race-specific. The major QTL on 5H was also found in adult plants under
      field conditions in three years (explaining up to 55%) and the 7H QTL was found
      in field trials in one year. Additional adult plant resistance QTL on 3H, 6H and
      7H were significant in single years. The resistance on chromosomes 3H, 5H, 6H and
      7H originates from the more resistant parent Lavrans, while the resistance on 4H
      is conferred by Arve. The genetic markers associated with the QTL found in this
      study will benefit marker-assisted selection for resistance against net blotch.

PMID- 28448538
TI  - Combined lipidomic and proteomic analysis of isolated human islets exposed to
      palmitate reveals time-dependent changes in insulin secretion and lipid
      metabolism.
AB  - Studies on the pathophysiology of type 2 diabetes mellitus (T2DM) have linked the
      accumulation of lipid metabolites to the development of beta-cell dysfunction and
      impaired insulin secretion. In most in vitro models of T2DM, rodent islets or
      beta-cell lines are used and typically focus is on specific cellular pathways or
      organs. Our aim was to, firstly, develop a combined lipidomics and proteomics
      approach for lipotoxicity in isolated human islets and, secondly, investigate if
      the approach could delineate novel and/ or confirm reported mechanisms of
      lipotoxicity. To this end isolated human pancreatic islets, exposed to
      chronically elevated palmitate concentrations for 0, 2 and 7 days, were
      functionally characterized and their levels of multiple targeted lipid and
      untargeted protein species determined. Glucose-stimulated insulin secretion from
      the islets increased on day 2 and decreased on day 7. At day 7 islet insulin
      content decreased and the proinsulin to insulin content ratio doubled. Amounts of
      cholesterol, stearic acid, C16 dihydroceramide and C24:1 sphingomyelin, obtained
      from the lipidomic screen, increased time-dependently in the palmitate-exposed
      islets. The proteomic screen identified matching changes in proteins involved in
      lipid biosynthesis indicating up-regulated cholesterol and lipid biosynthesis in
      the islets. Furthermore, proteins associated with immature secretory granules
      were decreased when palmitate exposure time was increased despite their high
      affinity for cholesterol. Proteins associated with mature secretory granules
      remained unchanged. Pathway analysis based on the protein and lipid expression
      profiles implicated autocrine effects of insulin in lipotoxicity. Taken together
      the study demonstrates that combining different omics approaches has potential in
      mapping of multiple simultaneous cellular events. However, it also shows that
      challenges exist for effectively combining lipidomics and proteomics in primary
      cells. Our findings provide insight into how saturated fatty acids contribute to
      islet cell dysfunction by affecting the granule maturation process and
      confirmation in human islets of some previous findings from rodent islet and cell
      line studies.

PMID- 28448539
TI  - Causal relationship between obesity and serum testosterone status in men: A bi
      directional mendelian randomization analysis.
AB  - CONTEXT: Obesity in men is associated with low serum testosterone and both are
      associated with several diseases and increased mortality. OBJECTIVES: Examine the
      direction and causality of the relationship between body mass index (BMI) and
      serum testosterone. DESIGN: Bi-directional Mendelian randomization (MR) analysis
      on prospective cohorts. SETTING: Five cohorts from Denmark, Germany and Sweden
      (Inter99, SHIP, SHIP Trend, GOOD and MrOS Sweden). PARTICIPANTS: 7446 Caucasian
      men, genotyped for 97 BMI-associated SNPs and three testosterone-associated SNPs.
      MAIN OUTCOME MEASURES: BMI and serum testosterone adjusted for age, smoking, time
      of blood sampling and site. RESULTS: 1 SD genetically instrumented increase in
      BMI was associated with a 0.25 SD decrease in serum testosterone (IV ratio: 
      0.25, 95% CI: -0.42--0.09, p = 2.8*10-3). For a body weight reduction altering
      the BMI from 30 to 25 kg/m2, the effect would equal a 13% increase in serum
      testosterone. No association was seen for genetically instrumented testosterone
      with BMI, a finding that was confirmed using large-scale data from the GIANT
      consortium (n = 104349). CONCLUSIONS: Our results suggest that there is a causal
      effect of BMI on serum testosterone in men. Population level interventions to
      reduce BMI are expected to increase serum testosterone in men.

PMID- 28448540
TI  - Bruchid egg induced transcript dynamics in developing seeds of black gram (Vigna
      mungo).
AB  - Black gram (Vigna mungo) seeds are a rich source of digestible proteins, however,
      during storage these seeds are severely damaged by bruchids (Callosobruchus
      spp.), reducing seed quality and yield losses. Most of the cultivated genotypes
      of black gram are susceptible to bruchids, however, few tolerant genotypes have
      also been identified but the mechanism of tolerance is poorly understood. We
      employed Suppression Subtractive Hybridization (SSH) to identify specifically,
      but rarely expressed bruchid egg induced genes in black gram. In this study,
      Suppression Subtractive Hybridization (SSH) library was constructed to study the
      genes involved in defense response in black gram against bruchid infestation. An
      EST library of 277 clones was obtained for further analyses. Based on CAP3
      assembly, 134 unigenes were computationally annotated using Blast2GOPRO software.
      In all, 20 defense related genes were subject to quantitative PCR analysis (qPCR)
      out of which 12 genes showed up-regulation in developing seeds of the pods
      oviposited by bruchids. Few major defense genes like defensin, pathogenesis
      related protein (PR), lipoxygenase (LOX) showed high expression levels in the
      oviposited population when compared with the non-oviposited plants. This is the
      first report on defense related gene transcript dynamics during the bruchid-black
      gram interaction using SSH library. This library would be useful to clone defense
      related gene(s) such as defensin as represented in our library for crop
      improvement.

PMID- 28448541
TI  - Complementary and alternative medicine (CAM) use and delays in presentation and
      diagnosis of breast cancer patients in public hospitals in Malaysia.
AB  - Complementary and alternative medicine (CAM) is widely used among the breast
      cancer patients in Malaysia. Delays in presentation, diagnosis and treatment have
      been shown to impact the disease prognosis. There is considerable use of CAM
      amongst breast cancer patients. CAM use has been cited as a cause of delay in
      diagnosis and treatments in qualitative studies, however there had not been any
      confirmatory study that confirms its impact on delays. The purpose of this study
      was to evaluate whether the use of CAM among newly diagnosed breast cancer
      patients was associated with delays in presentation, diagnosis or treatment of
      breast cancer. This multi-centre cross-sectional study evaluating the time points
      of the individual breast cancer patients' journey from first visit, resolution of
      diagnosis and treatments was conducted in six public hospitals in Malaysia. All
      newly diagnosed breast cancer patients from 1st January to 31st December 2012
      were recruited. Data were collected through medical records review and patient
      interview by using a structured questionnaire. Complementary and alternative
      medicine (CAM) was defined as the use of any methods and products not included in
      conventional allopathic medicine before commencement of treatments. Presentation
      delay was defined as time taken from symptom discovery to first presentation of
      more than 3 months. The time points were categorised to diagnosis delay was
      defined as time taken from first presentation to diagnosis of more than 1 month
      and treatment delay was defined as time taken from diagnosis to initial treatment
      of more than 1 month. Multiple logistic regression was used for analysis. A total
      number of 340 patients participated in this study. The prevalence of CAM use was
      46.5% (n = 158). Malay ethnicity (OR 3.32; 95% CI: 1.85, 5.97) and not
      interpreting symptom as cancerous (OR 1.79; 95% CI: 1.10, 2.92) were
      significantly associated with CAM use. The use of CAM was associated with delays
      in presentation (OR 1.65; 95% CI: 1.05, 2.59), diagnosis (OR 2.42; 95% CI: 1.56,
      3.77) and treatment of breast cancer (OR 1.74; 95% CI: 1.11, 2.72) on univariate
      analyses. However, after adjusting with other covariates, CAM use was associated
      with delays in presentation (OR 1.71; 95% CI: 1.05, 2.78) and diagnosis (OR 2.58;
      95% CI: 1.59, 4.17) but not for treatment of breast cancer (OR 1.58; 95% CI:
      0.98, 2.55). The prevalence of CAM use among the breast cancer patients was high.
      Women of Malay ethnicity and not interpreting symptom as cancerous were
      significantly associated with CAM use. The use of CAM is significantly associated
      with delay in presentation and resolution of diagnosis. This study suggests
      further evaluation of access to breast cancer care is needed as poor access may
      cause the use of CAM. However, since public hospitals in Malaysia are heavily
      subsidized and readily available to the population, CAM use may impact delays in
      presentation and diagnosis.

PMID- 28448542
TI  - Diminished plasma levels of common gamma-chain cytokines in pulmonary
      tuberculosis and reversal following treatment.
AB  - BACKGROUND: The immune response to tuberculosis (TB) is T cell dependent. T cells
      are the major facilitators of protection and effector functions with CD4+ T cells
      being the most important players, followed by CD8+ T cells. The common gamma
      chain cytokines IL-2, IL-7, IL-15, and IL-21 play a vital role in peripheral T
      cell growth and survival. However, the role of common gamma-chain cytokines in
      pulmonary TB (PTB) is poorly understood. AIM AND METHODS: To examine the
      association of circulating common gamma-chain cytokines with TB disease or
      infection, we examined the systemic levels of IL-2, IL-7, IL-15, and IL-21 in
      individuals with PTB, latent TB (LTB) or no TB infection (NTB). We also examined
      the levels of these cytokines in PTB individuals before and after anti
      tuberculosis treatment. RESULTS: Circulating levels of IL-2, IL-7 and IL-21 were
      significantly diminished in PTB compared to LTB or NTB individuals. Moreover, TB
      antigen stimulated whole blood also exhibited diminished levels of common gamma
      chain cytokines in PTB compared to LTB or NTB individuals. The plasma levels of
      common gamma-chain cytokines exhibited no significant association with the
      severity or extent of TB disease or with bacterial burdens. However, upon
      standard anti-TB treatment, both the systemic as well as the TB antigen
      stimulated levels of IL-2, IL-7 and IL-21 were significantly increased in PTB
      individuals. CONCLUSION: Therefore our data demonstrate that diminished levels of
      common gamma-chain cytokines are a common characteristic of PTB and potentially
      highlight the importance of boosting these responses to improve treatment
      outcomes.

PMID- 28448543
TI  - Heterologous expression of a thermophilic diacylglycerol acyltransferase triggers
      triglyceride accumulation in Escherichia coli.
AB  - Triglycerides (TAGs), the major storage molecules of metabolic energy and source
      of fatty acids, are produced as single cell oil by some oleogenic microorganisms.
      However, these microorganisms require strict culture conditions, show low carbon
      source flexibilities, lack efficient genetic modification tools and in some cases
      pose safety concerns. TAGs have essential applications such as behaving as a
      source for added-value fatty acids or giving rise to the production of biodiesel.
      Hence, new alternative methods are urgently required for obtaining these oils. In
      this work we describe TAG accumulation in the industrially appropriate
      microorganism Escherichia coli expressing the heterologous enzyme tDGAT, a wax
      ester synthase/triacylglycerol:acylCoA acyltranferase (WS/DGAT). With this
      purpose, we introduce a codon-optimized gene from the thermophilic actinomycete
      Thermomonospora curvata coding for a WS/DGAT into different E. coli strains,
      describe the metabolic effects associated to the expression of this protein and
      evaluate neutral lipid accumulation. We observe a direct relation between the
      expression of this WS/DGAT and TAG production within a wide range of culture
      conditions. More than 30% TAGs were detected within the bacterial neutral lipids
      in 90 minutes after induction. TAGs were observed to be associated with the
      hydrophobic enzyme while forming round intracytoplasmic bodies, which could
      represent a bottleneck for lipid accumulation in E. coli. We detected an increase
      of almost 3-fold in the monounsaturated fatty acids (MUFA) occurring in the
      recombinant strains. These MUFA were predominant in the accumulated TAGs
      achieving 46% of the TAG fatty acids. These results set the basis for further
      research on the achievement of a suitable method towards the sustainable
      production of these neutral lipids.

PMID- 28448544
TI  - Comparing herbaceous plant communities in active and passive riparian
      restoration.
AB  - Understanding the efficacy of passive (reduction or cessation of environmental
      stress) and active (typically involving planting or seeding) restoration
      strategies is important for the design of successful revegetation of degraded
      riparian habitat, but studies explicitly comparing restoration outcomes are
      uncommon. We sampled the understory herbaceous plant community of 103 riparian
      sites varying in age since restoration (0 to 39 years) and revegetation technique
      (active, passive, or none) to compare the utility of different approaches on
      restoration success across sites. We found that landform type, percent shade, and
      summer flow helped explain differences in the understory functional community
      across all sites. In passively restored sites, grass and forb cover and richness
      were inversely related to site age, but in actively restored sites forb cover and
      richness were inversely related to site age. Native cover and richness were lower
      with passive restoration compared to active restoration. Invasive species cover
      and richness were not significantly different across sites. Although some of our
      results suggest that active restoration would best enhance native species in
      degraded riparian areas, this work also highlights some of the context-dependency
      that has been found to mediate restoration outcomes. For example, since the
      effects of passive restoration can be quite rapid, this approach might be more
      useful than active restoration in situations where rapid dominance of pioneer
      species is required to arrest major soil loss through erosion. As a result, we
      caution against labeling one restoration technique as better than another.
      Managers should identify ideal restoration outcomes in the context of historic
      and current site characteristics (as well as a range of acceptable alternative
      states) and choose restoration approaches that best facilitate the achievement of
      revegetation goals.

PMID- 28448545
TI  - Vitamin D3-induced hypercalcemia increases carbon tetrachloride-induced
      hepatotoxicity through elevated oxidative stress in mice.
AB  - The aim of this study was to determine whether calcium potentiates acute carbon
      tetrachloride (CCl4) -induced toxicity. Elevated calcium levels were induced in
      mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that
      has previously been shown to induce hypercalcemia in human and animal models. As
      seen previously, mice injected with CCl4 exhibited increased plasma levels of
      alanine aminotransferase, aspartate aminotransferase, and creatinine; transient
      body weight loss; and increased lipid peroxidation along with decreased total
      antioxidant power, glutathione, ATP, and NADPH. Pre-treatment of these animals
      with V.D3 caused further elevation of the values of these liver functional
      markers without altering kidney functional markers; continued weight loss; a
      lower lethal threshold dose of CCl4; and enhanced effects on lipid peroxidation
      and total antioxidant power. In contrast, exposure to V.D3 alone had no effect on
      plasma markers of liver or kidney damage or on total antioxidant power or lipid
      peroxidation. The potentiating effect of V.D3 was positively correlated with
      elevation of hepatic calcium levels. Furthermore, direct injection of CaCl2 also
      enhanced CCl4-induced hepatic injury. Since CaCl2 induced hypercalcemia
      transiently (within 3 h of injection), our results suggest that calcium enhances
      the CCl4-induced hepatotoxicity at an early stage via potentiation of oxidative
      stress.

PMID- 28448546
TI  - Opium use during pregnancy and risk of preterm delivery: A population-based
      cohort study.
AB  - BACKGROUND: Use of narcotic or "recreational" drugs has been associated with
      adverse pregnancy outcomes such as preterm delivery. However, the associations
      might be confounded by other factors related to high-risk behaviours. This is the
      first study to investigate the association between traditional opium use during
      pregnancy and risk of preterm delivery. METHOD AND FINDINGS: We performed a
      population-based cohort study in the rural areas of the Golestan province, Iran
      between 2008 and 2010. We randomly selected 920 women who used (usually smoked)
      opium during pregnancy and 920 women who did not. Logistic regression models were
      used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the
      associations between the opium use during pregnancy and preterm delivery and
      adjustment was made for potential confounding factors. This study shows compared
      with non-use of opium and tobacco, use of only opium during pregnancy was
      associated with an increased risk of preterm delivery (OR = 1.56; 95% CI 1.05
      2.32), and the risk was more than two-fold increased among dual users of opium
      and tobacco (OR = 2.31; 95% CI 1.37-3.90). We observed that opium use only was
      associated with a doubled risk for preterm caesarean delivery (OR = 2.05; 95% CI
      1.10-3.82) but not for preterm vaginal delivery (OR = 1.25; 95% CI 0.75-2.07).
      Dual use of opium and tobacco was associated with a substantially increased risk
      of vaginal preterm delivery (OR = 2.58; 95% CI 1.41-4.71). CONCLUSIONS: Opium use
      during pregnancy among non-tobacco smokers is associated with an increased risk
      of preterm caesarean delivery, indicating an increased risk of a compromised
      foetus before or during labour. Women who use both opium and smoked during
      pregnancy have an increased risk of preterm vaginal delivery, indicating an
      increased risk of spontaneous preterm delivery.

PMID- 28448547
TI  - Circulating leptin and adiponectin are associated with insulin resistance in
      healthy postmenopausal women with hot flashes.
AB  - INTRODUCTION: Hot flashes have been postulated to be linked to the development of
      metabolic disorders. This study aimed to evaluate the relationship between hot
      flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese
      postmenopausal women. PARTICIPANTS AND DESIGN: In this cross-sectional study, a
      total of 151 women aged 45-60 years were stratified into one of three groups
      according to hot-flash status over the past three months: never experienced hot
      flashes (Group N), mild-to-moderate hot flashes (Group M), and severe hot flashes
      (Group S). Variables measured in this study included clinical parameters, hot
      flash experience, fasting levels of circulating glucose, lipid profiles, plasma
      insulin, and adipocyte-derived hormones. Multiple linear regression analysis was
      used to evaluate the associations of hot flashes with adipocyte-derived hormones,
      and with insulin resistance. SETTINGS: The study was performed in a hospital
      medical center. RESULTS: The mean (standard deviation) of body-mass index was
      22.8(2.7) for Group N, 22.6(2.6) for Group M, and 23.5(2.4) for Group S,
      respectively. Women in Group S displayed statistically significantly higher
      levels of leptin, fasting glucose, and insulin, and lower levels of adiponectin
      than those in Groups M and N. Multivariate linear regression analysis revealed
      that hot-flash severity was significantly associated with higher leptin levels,
      lower adiponectin levels, and higher leptin-to-adiponectin ratio. Univariate
      linear regression analysis revealed that hot-flash severity was strongly
      associated with a higher HOMA-IR index (% difference, 58.03%; 95% confidence
      interval, 31.00-90.64; p < 0.001). The association between hot flashes and HOMA
      IR index was attenuated after adjusting for leptin or adiponectin and was no
      longer significant after simultaneously adjusting for leptin and adiponectin.
      CONCLUSION: The present study provides evidence that hot flashes are associated
      with insulin resistance in postmenopausal women. It further suggests that hot
      flash association with insulin resistance is dependent on the combination of
      leptin and adiponectin variables.

PMID- 28448548
TI  - Altered striatal endocannabinoid signaling in a transgenic mouse model of
      spinocerebellar ataxia type-3.
AB  - Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant
      inherited ataxia. We recently found that the endocannabinoid system is altered in
      the post-mortem cerebellum of SCA-3 patients, and similar results were also found
      in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given
      that the neuropathology of SCA-3 is not restricted to these two brain regions but
      rather, it is also evident in other structures (e.g., the basal ganglia), we
      studied the possible changes to endocannabinoid signaling in the striatum of
      these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination,
      balance and they have an abnormal gait, reflecting a cerebellar/brainstem
      neuropathology. However, they also show dystonia-like behavior (limb clasping)
      that may be related to the malfunction/deterioration of specific neurons in the
      striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant
      mice, accompanied by a reduction in glial glutamate transporters that could
      potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling,
      no changes in CB2 receptors were evident, yet an important reduction in CB1
      receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors
      was presumed to occur in striatal afferent and efferent neurons, also potentially
      aggravating excitotoxicity. We also measured the endocannabinoid lipids in the
      striatum and despite a marked increase in the FAAH enzyme in this area, no
      overall changes in these lipids were found. Collectively, these studies confirm
      that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding
      to the equivalent changes found in other strongly affected CNS structures in this
      type of ataxia (i.e.: the cerebellum and brainstem). These data open the way to
      search for drugs that might correct these changes.

PMID- 28448549
TI  - There was not, they did not: May negation cause the negated ideas to be
      remembered as existing?
AB  - In this article we demonstrate that negation of ideas can have paradoxical
      effects, possibly leading the listener to believe that the negated ideas actually
      existed. In Experiment 1, participants listened to a description of a house, in
      which some objects were mentioned, some were negated, and some were not mentioned
      at all. When questioned about the existence of these objects a week later, the
      participants gave more false positives for items that were negated in the
      original material than for items that were not mentioned at all, an effect we
      call negation related false memories (NRFM). The NRFM effect was replicated again
      in Experiment 2 with a sample of five and six year-old children. Experiment 3
      confirmed NRFM in the case of negated actions. The results are discussed in terms
      of retention hypothesis, as well as the theory that negation can activate a
      representation of an entity and behaviour. It is also indicated that future
      research is needed to ensure that it is indeed negation which caused false
      alarms, not merely mentioning an object.

PMID- 28448550
TI  - Priority target conditions for algorithms for monitoring children's growth:
      Interdisciplinary consensus.
AB  - BACKGROUND: Growth monitoring of apparently healthy children aims at early
      detection of serious conditions through the use of both clinical expertise and
      algorithms that define abnormal growth. Optimization of growth monitoring
      requires standardization of the definition of abnormal growth, and the selection
      of the priority target conditions is a prerequisite of such standardization.
      OBJECTIVE: To obtain a consensus about the priority target conditions for
      algorithms monitoring children's growth. METHODS: We applied a formal consensus
      method with a modified version of the RAND/UCLA method, based on three phases
      (preparatory, literature review, and rating), with the participation of expert
      advisory groups from the relevant professional medical societies (ranging from
      primary care providers to hospital subspecialists) as well as parent
      associations. We asked experts in the pilot (n = 11), reading (n = 8) and rating
      (n = 60) groups to complete the list of diagnostic classification of the European
      Society for Paediatric Endocrinology and then to select the conditions meeting
      the four predefined criteria of an ideal type of priority target condition.
      RESULTS: Strong agreement was obtained for the 8 conditions selected by the
      experts among the 133 possible: celiac disease, Crohn disease, craniopharyngioma,
      juvenile nephronophthisis, Turner syndrome, growth hormone deficiency with
      pituitary stalk interruption syndrome, infantile cystinosis, and hypothalamic
      optochiasmatic astrocytoma (in decreasing order of agreement). CONCLUSION: This
      national consensus can be used to evaluate the algorithms currently suggested for
      growth monitoring. The method used for this national consensus could be re-used
      to obtain an international consensus.

PMID- 28448551
TI  - Characterization of physiological defects in adult SIRT6-/- mice.
AB  - The NAD+-dependent SIRT6 deacetylase was shown to be a major regulator of
      lifespan and healthspan. Mice deficient for SIRT6 develop a premature aging
      phenotype and metabolic defects, and die before four weeks of age. Thus, the
      effect of SIRT6 deficiency in adult mice is unknown. Here we show that SIRT6-/-
      mice in mixed 129/SvJ/BALB/c background reach adulthood, allowing examination of
      SIRT6-related metabolic and developmental phenotypes in adult mice. In this mixed
      background, at 200 days of age, more than 80% of the female knock-out mice were
      alive whereas only 10% of male knock-out mice survived. In comparison to their
      wild-type littermates, SIRT6 deficient mice have reduced body weight, increased
      glucose uptake and exhibit an age-dependent progressive impairment of retinal
      function accompanied by thinning of retinal layers. Together, these results
      demonstrate a role for SIRT6 in metabolism and age-related ocular changes in
      adult mice and suggest a gender specific regulation of lifespan by SIRT6.

PMID- 28448552
TI  - Transcriptomic analysis of the hepatic response to stress in the red cusk-eel
      (Genypterus chilensis): Insights into lipid metabolism, oxidative stress and
      liver steatosis.
AB  - Teleosts exhibit a broad divergence in their adaptive response to stress,
      depending on the magnitude, duration, and frequency of stressors and the species
      receiving the stimulus. We have previously reported that the red cusk-eel
      (Genypterus chilensis), an important marine farmed fish, shows a physiological
      response to stress that results in increased skeletal muscle atrophy mediated by
      over-expression of components of the ubiquitin proteasome and autophagy-lysosomal
      systems. To better understand the systemic effects of stress on the red cusk-eel
      metabolism, the present study assessed the transcriptomic hepatic response to
      repetitive handling-stress. Using high-throughput RNA-seq, 259 up-regulated
      transcripts were found, mostly associated with angiogenesis, gluconeogenesis, and
      triacylglyceride catabolism. Conversely, 293 transcripts were down-regulated,
      associated to cholesterol biosynthesis, PPARalpha signaling, fatty acid
      biosynthesis, and glycolysis. This gene signature was concordant with hepatic
      metabolite levels and hepatic oxidative damage. Moreover, the increased plasmatic
      levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase) and AP
      (alkaline phosphatase), as well as liver histology suggest stress-induced liver
      steatosis. This study offers an integrative molecular and biochemical analysis of
      the hepatic response to handling-stress, and reveals unknown aspects of lipid
      metabolism in a non-model teleost.

PMID- 28448553
TI  - A computational toxicogenomics approach identifies a list of highly hepatotoxic
      compounds from a large microarray database.
AB  - The liver and the kidney are the most common targets of chemical toxicity, due to
      their major metabolic and excretory functions. However, since the liver is
      directly involved in biotransformation, compounds in many currently and normally
      used drugs could affect it adversely. Most chemical compounds are already labeled
      according to FDA-approved labels using DILI-concern scale. Drug Induced Liver
      Injury (DILI) scale refers to an adverse drug reaction. Many compounds do not
      exhibit hepatotoxicity at early stages of development, so it is important to
      detect anomalies at gene expression level that could predict adverse reactions in
      later stages. In this study, a large collection of microarray data is used to
      investigate gene expression changes associated with hepatotoxicity. Using TG
      GATEs a large-scale toxicogenomics database, we present a computational strategy
      to classify compounds by toxicity levels in human and animal models through
      patterns of gene expression. We combined machine learning algorithms with time
      series analysis to identify genes capable of classifying compounds by FDA
      approved labeling as DILI-concern toxic. The goal is to define gene expression
      profiles capable of distinguishing the different subtypes of hepatotoxicity. The
      study illustrates that expression profiling can be used to classify compounds
      according to different hepatotoxic levels; to label those that are currently
      labeled as undertemined; and to determine if at the molecular level, animal
      models are a good proxy to predict hepatotoxicity in humans.

PMID- 28448554
TI  - Evaluation of efficiency of controlled pollination based parentage analysis in a
      Larix gmelinii var. principis-rupprechtii Mayr. seed orchard.
AB  - Controlled pollination (CP) is an important tool for breeding programs to improve
      seed quality, as it rapidly generates desirable genotypes and maximizes genetic
      gains. However, few studies have evaluated the success rate of CP, especially in
      Larix gmelinii var. principis-rupprechtii Mayr. seed orchards. In this study, we
      estimated the rate of correct parentage in 257 CP progeny in an L. gmelinii var.
      principis-rupprechtii seed orchard from ten candidate parents using 13
      microsatellites. The parentage exclusion probabilities of all combined loci in
      the single parent and parent pair tests were > 0.99, which was sufficient to
      distinguish the relatedness of the sampled individuals. Comparing the maximum
      likelihood-based parentage analysis results with breeding records revealed that
      the percentages of correctly identified maternal and paternal parents were 22.6%
      and 35.0% at 95% CL, respectively, suggestive of parent mislabeling and pollen
      contamination in the CP population. We conducted a pedigree reconstruction by
      identifying the expected parents and assigned maternity, paternity, and parent
      pairs to 176 (68.5%), 199 (77.4%), and 132 (51.4%) progeny, respectively. This
      study provides a reference for future selection of elite genotypes for commercial
      production. To increase the efficiency of CP, molecular markers should be used to
      correctly identify individuals in seed orchards before conducting CP.

PMID- 28448555
TI  - Socio-demographic disparities in the utilisation of general practice services for
      Australian children - Results from a nationally representative longitudinal
      study.
AB  - OBJECTIVE: This study aimed to investigate the pattern of general practice
      services utilization for Australian children and to examine socio-demographic
      disparities in general practitioner (GP) visits. METHODS: We used the linked data
      from the nationally representative Longitudinal Study of Australian Children
      (LSAC) and the Medicare Australia claims data record. We used survey negative
      binomial and logistic regression to examine the socio-demographic factors
      associated with the utilisation of general practice services. RESULTS: The
      average number of annual GP visits gradually declined from 7.0 at 0-1 year old to
      2.4 at 5-8 years (p< .001 for trend) in the infant cohort and from 3.5 at 2-4
      years to 2.0 at 9-12 years (p < .001 for trend) in the child cohort. Girls were
      more likely to visit GPs than boys at 0-1 year old in the infant cohort (RR =
      1.06, 95%CI: 1.02-1.11) and at 2-4 years in the child cohort (RR = 1.09, 95%CI:
      1.04-1.14), but there were no differences at 2-4 to 5-8 year age periods in the
      infant cohort and at 5-8 to 9-12 year age period in the child cohort. Children
      from non-English speaking background were more likely to have a greater number of
      GP visits compared with their counterparts from English-speaking and Indigenous
      background up to eight year old in both cohorts (all p < .001). Children from
      families with the higher socio-economic position, children without private health
      insurance and children living in non-metropolitan were less likely to have GP
      consultations in both cohorts. Fair or poor parent-rated health status was
      associated with greater number of GP visits. CONCLUSION: Socio-demographic
      disparities existed in the utilisation of general practice services and varied at
      different age periods. Family socio-economic position, private health insurance
      coverage and region of residence strongly associates with the utilisation
      disparities over all age period. Further policy interventions are called to
      minimise the disparities in GP utilisation for children in Australian context.

PMID- 28448556
TI  - A highly specific and sensitive massive parallel sequencer-based test for somatic
      mutations in non-small cell lung cancer.
AB  - Molecular targeting therapy for non-small cell lung cancer (NSCLC) has clarified
      the importance of mutation testing when selecting treatment regimens. As a
      result, multiple-gene mutation tests are urgently needed. We developed a next
      generation sequencer (NGS)-based, multi-gene test named the MINtS for
      investigating driver mutations in both cytological specimens and snap-frozen
      tissue samples. The MINtS was used to investigate the EGFR, KRAS, BRAF genes from
      DNA, and the ERBB2, and the ALK, ROS1, and RET fusion genes from RNA. We focused
      on high specificity and sensitivity (>=0.99) and even included samples with a
      cancer cell content of 1%. The MINtS enables testing of more than 100 samples in
      a single run, making it possible to process a large number of samples submitted
      to a central laboratory, and reducing the cost for a single sample. We
      investigated 96 cytological samples and 190 surgically resected tissues, both of
      which are isolated in daily clinical practice. With the cytological samples, we
      compared the results for the EGFR mutation between the MINtS and the PNA-LNA PCR
      clamp test, and their results were 99% consistent. In the snap-frozen tissue
      samples, 188/190 (99%) samples were successfully analyzed for all genes
      investigated using both DNA and RNA. Then, we used 200 cytological samples that
      were serially isolated in clinical practice to assess RNA quality. Using our
      procedure, 196 samples (98%) provided high-quality RNA suitable for analysis with
      the MINtS. We concluded that the MINtS test system is feasible for analyzing
      "druggable" genes using cytological samples and snap-frozen tissue samples. The
      MINtS will fill a needs for patients for whom only cytological specimens are
      available for genetic testing.

PMID- 28448557
TI  - Are sex differences in fundamental motor skills uniform throughout the entire
      preschool period?
AB  - The aim of this study was to assess differences in fundamental motor skills (FMS)
      proficiency between boys and girls of each age group, independently, across the
      entire preschool period. Using the Movement Assessment Battery for Children
      second edition, FMS proficiency was tested in 325 preschoolers (4.9 +/- 1.1 y,
      range 3-6) using a cross-sectional design. Compared to boys of the same age, 3-
      and 4-year-old girls had greater total (p < .01), fine motor skill (p < .01), and
      balance scores (p < .05). There were no sex differences for total test or balance
      scores in 5- and 6-year-olds, but 6-year-old boys outperformed girls in aiming
      and catching (p < .001). These data not only agree with previous research in that
      sex differences in FMS proficiency exist in preschool children, but the data also
      show that differences may not be uniform throughout the whole preschool period
      when analyzing by age. To avoid under- or overestimating FMS proficiency and
      subsequently prescribing inaccurate motor intervention programs, FMS proficiency
      normative values should be age- and sex-specific throughout the entire preschool
      period.

PMID- 28448558
TI  - The herpevac trial for women: Sequence analysis of glycoproteins from viruses
      obtained from infected subjects.
AB  - The Herpevac Trial for Women revealed that three dose HSV-2 gD vaccine was 58%
      protective against culture-positive HSV-1 genital disease, but it was not
      protective against HSV-2 infection or disease. To determine whether vaccine
      induced immune responses had selected for a particular gD sequence in strains
      infecting vaccine recipients compared with viruses infecting control subjects,
      genetic sequencing studies were carried out on viruses isolated from subjects
      infected with HSV-1 or HSV-2. We identified naturally occurring variants among
      the gD sequences obtained from 83 infected subjects. Unique or low frequency
      amino acid substitutions in the ectodomain of gD were found in 6 of 39 HSV-1
      infected subjects and in 7 of 44 HSV-2-infected subjects. However, no consistent
      amino acid change was identified in isolates from gD-2 vaccine recipients
      compared with infected placebo recipients. gC and gE surround and partially
      shield gD from neutralizing antibody, and gB also participates closely in the
      viral entry process. Therefore, these genes were sequenced from a number of
      isolates to assess whether sequence variation may alter protein conformation and
      influence the virus strain's capacity to be neutralized by vaccine-induced
      antibody. gC and gE genes sequenced from HSV-1-infected subjects showed more
      variability than their HSV-2 counterparts. The gB sequences of HSV-1 oral
      isolates resembled each other more than they did gB sequences rom genital
      isolates. Overall, however, comparison of glycoprotein sequences of viral
      isolates obtained from infected subjects did not reveal any singular selective
      pressure on the viral cell attachment protein or surrounding glycoproteins due to
      administration of gD-2 vaccine.

PMID- 28448559
TI  - HexA is a versatile regulator involved in the control of phenotypic heterogeneity
      of Photorhabdus luminescens.
AB  - Phenotypic heterogeneity in microbial communities enables genetically identical
      organisms to behave differently even under the same environmental conditions.
      Photorhabdus luminescens, a bioluminescent Gram-negative bacterium, contains a
      complex life cycle, which involves a symbiotic interaction with nematodes as well
      as a pathogenic association with insect larvae. P. luminescens exists in two
      distinct phenotypic cell types, designated as the primary (1 degrees ) and
      secondary (2 degrees ) cells. The 1 degrees  cells are bioluminescent, pigmented
      and can support nematode growth and development. Individual 1 degrees  cells
      undergo phenotypic switching after prolonged cultivation and convert to 2 degrees
      cells, which lack the 1 degrees  specific phenotypes. The LysR-type regulator
      HexA has been described as major regulator of this switching process. Here we
      show that HexA controls phenotypic heterogeneity in a versatile way, directly and
      indirectly. Expression of hexA is enhanced in 2 degrees  cells, and the
      corresponding regulator inhibits 1 degrees  specific traits in 2 degrees  cells.
      HexA does not directly affect bioluminescence, a predominant 1 degrees  specific
      phenotype. Since the respective luxCDABE operon is repressed at the post
      transcriptional level and transcriptional levels of the RNA chaperone gene hfq
      are also enhanced in 2 degrees  cells, small regulatory RNAs are presumably
      involved that are under control of HexA. Another phenotypic trait that is
      specific for 1 degrees  cells is quorum sensing mediated cell clumping. The
      corresponding pcfABCDEF operon could be identified as the first direct target of
      HexA, since the regulator binds to the pcfA promoter region and thereby blocks
      expression of the target operon. In summary, our data show that HexA fulfills the
      task as repressor of 1 degrees  specific features in 2 degrees  cells in a
      versatile way and gives first insights into the complexity of regulating
      phenotypic heterogeneity in Photorhabdus bacteria.

PMID- 28448560
TI  - Activity of xyloglucan endotransglucosylases/hydrolases suggests a role during
      host invasion by the parasitic plant Cuscuta reflexa.
AB  - The parasitic vines of the genus Cuscuta form haustoria that grow into other
      plants and connect with their vascular system, thus allowing the parasite to feed
      on its host. A major obstacle that meets the infection organ as it penetrates the
      host tissue is the rigid plant cell wall. In the present study, we examined the
      activity of xyloglucan endotransglucosylases/hydrolases (XTHs) during the host
      invasive growth of the haustorium. The level of xyloglucan endotransglucosylation
      (XET) activity was found to peak at the penetrating stage of Cuscuta reflexa on
      its host Pelargonium zonale. In vivo colocalization of XET activity and donor
      substrate demonstrated XET activity at the border between host and parasite. A
      test for secretion of XET-active enzymes from haustoria of C. reflexa
      corroborated this and further indicated that the xyloglucan-modifying enzymes
      originated from the parasite. A known inhibitor of XET, Coomassie Brilliant Blue
      R250, was shown to reduce the level of XET in penetrating haustoria of C.
      reflexa. Moreover, the coating of P. zonale petioles with the inhibitor compound
      lowered the number of successful haustorial invasions of this otherwise
      compatible host plant. The presented data indicate that the activity of Cuscuta
      XTHs at the host-parasite interface is essential to penetration of host plant
      tissue.

PMID- 28448561
TI  - Persistence and innovation effects in genetic and environmental factors in
      negative emotionality during infancy: A twin study.
AB  - BACKGROUND: Difficult temperament in infancy is a risk factor for forms of later
      internalizing and externalizing psychopathology, including depression and
      anxiety. A better understanding of the roots of difficult temperament requires
      assessment of its early development with a genetically informative design. The
      goal of this study was to estimate genetic and environmental contributions to
      individual differences in infant negative emotionality, their persistence over
      time and their influences on stability between 5 and 18 months of age. METHOD:
      Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male)
      recruited from birth. Mothers rated their twins for negative emotionality at 5
      and 18 months. Longitudinal analysis of stability and innovation between the two
      time points was performed in Mplus. RESULTS: There were substantial and similar
      heritability (approximately 31%) and shared environmental (57.3%) contributions
      to negative emotionality at both 5 and 18 months. The trait's interindividual
      stability across time was both genetically- and environmentally- mediated.
      Evidence of innovative effects (i.e., variance at 18 months independent from
      variance at 5 months) indicated that negative emotionality is developmentally
      dynamic and affected by persistent and new genetic and environmental factors at
      18 months. CONCLUSIONS: In the first two years of life, ongoing genetic and
      environmental influences support temperamental negative emotionality but new
      genetic and environmental factors also indicate dynamic change of those factors
      across time. A better understanding of the source and timing of factors on
      temperament in early development, and role of sex, could improve efforts to
      prevent related psychopathology.

PMID- 28448562
TI  - The impact of anti-drug antibodies on drug concentrations and clinical outcomes
      in rheumatoid arthritis patients treated with adalimumab, etanercept, or
      infliximab: Results from a multinational, real-world clinical practice, non
      interventional study.
AB  - OBJECTIVE: To assess the incidence of anti-drug antibodies (ADA) in patients with
      rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN),
      adalimumab (ADL), or infliximab (IFX), and determine the potential relationship
      with trough drug concentration, efficacy, and patient-reported outcomes. METHODS:
      This multi-national, non-interventional, cross-sectional study (NCT01981473)
      enrolled adult patients with RA treated continuously for 6-24 months with ETN,
      ADL, or IFX. ADA and trough drug concentrations were measured by independent
      assays <=2 days before the next scheduled dose. Efficacy measurements included
      Disease Activity Score 28-joint count (DAS28), low disease activity (LDA),
      remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories
      of injection site/infusion reactions, serum sickness, and thromboembolic events
      were collected. RESULTS: Baseline demographics of the 595 patients (ETN: n = 200;
      ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of
      treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively.
      All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4%
      patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX
      treated patients, those with ADA had significantly lower trough drug
      concentrations. There were negative correlations between trough drug levels and
      both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission
      rates were higher in patients without ADA. The rate of targeted medical events
      reported was low. CONCLUSION: ADA were detected in ADL- and IFX-treated but not
      ETN-treated patients. Patients without ADA generally showed numerically better
      clinical outcomes than those with ADA. TRIAL REGISTRATION: This study was
      registered on www.ClinicalTrials.gov (NCT01981473).

PMID- 28448563
TI  - Corticosteroids effects on LPS-induced rat inflammatory keratocyte cell model.
AB  - PURPOSE: Corticosteroids are efficient anti-inflammation treatments. However,
      there are still arguments on whether it should be used in keratitis. This study
      was to observe the effect of corticosteroids on keratocytes both in normal
      condition and inflammation status in vitro. METHODS: Rat keratocytes were
      cultured and used for examination. 10 MUg/ml lipopolysaccharide (LPS) was used to
      establish the inflammatory keratocyte cell model, and prednisolone acetate (PA),
      dexamethasone (Dex) and fluorometholone (Flu) were used as corticosteroids
      treatments. 5 d-growth curve and cell viabilities were assayed by CCK8, and cell
      morphologies and migration rate were studied. TNF-alpha, IL-6 and IL-1beta levels
      were examined by ELISA. Western blotting was used to quantified type VI collagen
      (Col VI) and matrix metalloproteinase 9 (MMP9) expressions, and
      immunofluorescence staining assays of Col I and Col VI were carried out. RESULTS:
      In normal condition, proliferation and migration of keratocytes were slightly
      influenced in PA, Dex and Flu groups. The secretion of Col I and Col VI was
      suppressed and MMP9 expression increased in corticosteroids groups. But no
      significant difference was seen in TNF-alpha, IL-6 and IL-1beta expression
      levels. In inflammatory status, TNF-alpha, IL-6 and MMP9 levels increased in LPS
      group, while they significantly decreased in corticosteroids groups. Although
      keratocytes viabilities and migration were slightly affected in 24 h, no
      significant differences were seen between LPS group and corticosteroids groups in
      5-d proliferation. Col I and Col VI secretion in LPS-keratocytes was maintained
      with corticosteroids treatments. CONCLUSIONS: Corticosteroids showed lightly
      effects on keratocytes proliferation and migration, but it successfully decreased
      TNF-alpha, IL-6 level and maintained the secretion of and Col I and Col VI, while
      suppressed the expression of MMP9 in LPS-induced keratocytes. PA was suggested to
      use in early stage of keratitis clinical treatment.

PMID- 28448564
TI  - Insights into the biochemical defence and methylation of the solitary bee Osmia
      rufa L: A foundation for examining eusociality development.
AB  - We examined age-related biochemical and histological changes in the fat bodies
      and hemolymph of Osmia rufa males and females. We analysed solitary bees during
      diapause, in October and in April; as well as the flying insects following
      diapause, in May and June. The trophocyte sizes, as well as the numbers of lipid
      droplets were the greatest at the beginning of diapause. Subsequently, they
      decreased along with age. Triglyceride and glucose concentrations systematically
      decreased in fat body cells but increased in the hemolymph from October to June.
      Concentrations/activities of (enzymatic and non-enzymatic) antioxidant and
      proteolytic systems, as well as phenoloxidase, aspartate aminotransferase,
      alanine aminotransferase and alkaline phosphatase levels were constant during the
      diapause, usually lower in the males than the females. Prior to the
      diapause/overwintering, the concentrations/activities of all the compounds were
      higher in the fat bodies than in the hemolymph. Later in the spring and in the
      summer, they increased in the hemolymph and on the body surfaces, while
      decreasing in the fat bodies. The global DNA methylation levels increased with
      age. Higher levels were always observed in the males than in the females. The
      study will promote better understanding of bee evolution and will be useful for
      the protection and management of solitary bees, with benefits to the environment
      and agriculture.

PMID- 28448565
TI  - Characteristics of human - sloth bear (Melursus ursinus) encounters and the
      resulting human casualties in the Kanha-Pench corridor, Madhya Pradesh, India.
AB  - Sloth bears (Melursus ursinus) caused the highest number of human deaths between
      2001 and 2015 and ranked second compared to other wild animals in causing human
      casualties in the Kanha-Pench corridor area. We studied the patterns of sloth
      bear attacks in the region to understand the reasons for conflict. We interviewed
      166 victims of sloth bear attacks which occurred between 2004 and 2016 and found
      that most attacks occurred in forests (81%), with the greatest number of those
      (42%) occurring during the collection of Non-Timber Forest Produce (NTFP), 15%
      during the collection of fuelwood and 13% during grazing of livestock. The
      remainder took place at forest edges or in agricultural fields (19%), most
      occurring when person(s) were working in fields (7%), defecating (5%), or engaged
      in construction work (3%). Most victims were between the ages of 31 to 50 (57%)
      and most (54%) were members of the Gond tribe. The majority of attacks occurred
      in summer (40%) followed by monsoon (35%) and winter (25%). Forty-four percent of
      victims were rescued by people, while 43% of the time bears retreated by
      themselves. In 60% of attacks, a single bear was involved, whereas 25% involved
      adult females with dependent cubs and the remainder (15%) of the cases involved a
      pair of bears. We discuss the compensation program for attack victims as well as
      other governmental programs which can help reduce conflict. Finally, we recommend
      short-term mitigation measures for forest-dependent communities.

PMID- 28448567
TI  - Memory underpinnings of future intentions: Would you like to see the sequel?
AB  - In two studies, we investigated the memory underpinnings of future intentions
      related to past hedonic experiences. Preceding research did not make clear
      whether the specific memory processes supporting the expression of intentions
      about the future involve global judgments of the past experience (general
      affective evaluations formed on-line) or judgments derived from the episodic
      recollection of the past. Adapting a correlational paradigm previously employed
      to study future intentions, and applying it to the experience of watching a
      movie, we comparatively tested the influence of global retrospective evaluations
      vs. episodic-derived evaluations on future intentions. In Study 1, in which the
      intentions involved a future experience that was very similar to an overall past
      one (e.g., seeing the movie sequel), the findings showed that participants relied
      only on global judgments to form future intentions. In Study 2, in which the
      global judgment on the past was less diagnostic because the future intentions
      referred to specific parts of the past experience (e.g., watching a movie
      centered on a minor character in the previously seen movie), the results
      indicated that relevant episodic memories provided an essential contribution to
      the prediction of future intentions. These findings are in agreement with the
      predictions of the accessibility-diagnosticity framework and they show that
      global judgments and episodic memories of a past experience contribute
      differentially to diverse kinds of future intentions.

PMID- 28448566
TI  - IL-33/ST2 pathway drives regulatory T cell dependent suppression of liver damage
      upon cytomegalovirus infection.
AB  - Regulatory T (Treg) cells dampen an exaggerated immune response to viral
      infections in order to avoid immunopathology. Cytomegaloviruses (CMVs) are
      herpesviruses usually causing asymptomatic infection in immunocompetent hosts and
      induce strong cellular immunity which provides protection against CMV disease. It
      remains unclear how these persistent viruses manage to avoid induction of
      immunopathology not only during the acute infection but also during life-long
      persistence and virus reactivation. This may be due to numerous viral
      immunoevasion strategies used to specifically modulate immune responses but also
      induction of Treg cells by CMV infection. Here we demonstrate that liver Treg
      cells are strongly induced in mice infected with murine CMV (MCMV). The depletion
      of Treg cells results in severe hepatitis and liver damage without alterations in
      the virus load. Moreover, liver Treg cells show a high expression of ST2, a
      cellular receptor for tissue alarmin IL-33, which is strongly upregulated in the
      liver of infected mice. We demonstrated that IL-33 signaling is crucial for Treg
      cell accumulation after MCMV infection and ST2-deficient mice show a more
      pronounced liver pathology and higher mortality compared to infected control
      mice. These results illustrate the importance of IL-33 in the suppressive
      function of liver Treg cells during CMV infection.

PMID- 28448568
TI  - Inhibitory effects of fenretinide metabolites N-[4-methoxyphenyl]retinamide (MPR)
      and 4-oxo-N-(4-hydroxyphenyl)retinamide (3-keto-HPR) on fenretinide molecular
      targets beta-carotene oxygenase 1, stearoyl-CoA desaturase 1 and dihydroceramide
      Delta4-desaturase 1.
AB  - The therapeutic capacity of fenretinide (N-[4-hydroxyphenyl] retinamide; 4-HPR)
      has been demonstrated for several conditions, including cancer, obesity,
      diabetes, and ocular disease. Yet, the mechanisms of action for its pleiotropic
      effects are still undefined. We hypothesized that investigation of two of the
      major physiological metabolites of fenretinide, N-[4-methoxyphenyl]retinamide
      (MPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (3-keto-HPR), might begin to
      resolve the multifaceted effects of this synthetic retinoid. We analyzed the
      effects of fenretinide, MPR, 3-keto-HPR, and the non-retinoid RBP4 ligand A1120,
      on the activity of known targets of fenretinide, stearoyl-CoA desaturase 1 (SCD1)
      and dihydroceramide Delta4-desaturase 1 (DES1) in ARPE-19 cells, and purified
      recombinant mouse beta-carotene oxygenase 1 (BCO1) in vitro. Lipids and retinoids
      were extracted and quantified by liquid chromatography-mass spectrometry and
      reversed phase HPLC, respectively. The data demonstrate that while fenretinide is
      an inhibitor of the activities of these three enzymes, that 3-keto-HPR is a more
      potent inhibitor of all three enzymes, potentially mediating most of the in vivo
      beneficial effects of fenretinide. However, while MPR does not affect SCD1 and
      DES1 activity, it is a potent specific inhibitor of BCO1. We conclude that a
      deeper understanding of the mechanisms of action of fenretinide and its
      metabolites provides new avenues for therapeutic specificity. For example,
      administration of 3-keto-HPR instead of fenretinide may be preferential if
      inhibition of SCD1 or DES1 activity is the goal (cancer), while MPR may be better
      for BCO1 modulation (carotenoid metabolism). Continued investigation of
      fenretinide metabolites in the context of fenretinide's various therapeutic uses
      will begin to resolve the pleotropic nature of this compound.

PMID- 28448569
TI  - Dynamics and complexity of body temperature in preterm infants nursed in
      incubators.
AB  - BACKGROUND: Poor control of body temperature is associated with mortality and
      major morbidity in preterm infants. We aimed to quantify its dynamics and
      complexity to evaluate whether indices from fluctuation analyses of temperature
      time series obtained within the first five days of life are associated with
      gestational age (GA) and body size at birth, and presence and severity of typical
      comorbidities of preterm birth. METHODS: We recorded 3h-time series of body
      temperature using a skin electrode in incubator-nursed preterm infants. We
      calculated mean and coefficient of variation of body temperature, scaling
      exponent alpha (Talpha) derived from detrended fluctuation analysis, and sample
      entropy (TSampEn) of temperature fluctuations. Data were analysed by multilevel
      multivariable linear regression. RESULTS: Data of satisfactory technical quality
      were obtained from 285/357 measurements (80%) in 73/90 infants (81%) with a mean
      (range) GA of 30.1 (24.0-34.0) weeks. We found a positive association of Talpha
      with increasing levels of respiratory support after adjusting for GA and birth
      weight z-score (p<0.001; R2 = 0.38). CONCLUSION: Dynamics and complexity of body
      temperature in incubator-nursed preterm infants show considerable associations
      with GA and respiratory morbidity. Talpha may be a useful marker of autonomic
      maturity and severity of disease in preterm infants.

PMID- 28448570
TI  - Disease burden for patients with primary immunodeficiency diseases identified at
      reference hospitals in Guanajuato, Mexico.
AB  - BACKGROUND: In addition to the deleterious effect on health, there is
      considerable economic and psychosocial morbidity associated with primary
      immunodeficiency diseases (PID). Also, the cost of a late diagnosis frequently
      results in a heavy disease burden on the patient. The objective of this study was
      to collect and analyze data on patients with PID in the state of Guanajuato in
      Mexico, to indirectly estimate the burden of the disease. METHODS: An
      observational, longitudinal, and comparative study was conducted. A total of 44
      patients were included and grouped according to the updated classification of
      PID. RESULTS: The median time elapsed from the onset of symptoms to the reference
      and diagnosis by a tertiary hospital was of 2.17 (IQR = 6.44) years. Before
      diagnosis, the number of hospitalizations/year per patient was 0.86 (IQR = 2.28),
      the number of visit to emergency room/year per patient was 0.92 (IQR = 1.77), the
      number of doctor's visits/year per patient was 15 (IQR = 11.25), whereas the
      school/work absence days per patient were reported in 52.72 (IQR = 56.35) days
      per year. After diagnosis, 20 patients (45.45%) received IVIG replacement
      therapy, and all of them presented a significant improvement (p <0.05) in all the
      mentioned variables. Characteristically, even when patients with PID received
      IVIG, there was still an important disease burden when comparing them against
      healthy controls. Complications secondary to PID were detected in 19 patients
      (43.18%). The reported overall mortality rate was 6.82% (n = 3). CONCLUSIONS: We
      were able to indirectly estimate an important disease burden in patients with
      PID; which is considered to be preventable, at least in part, with effective
      interventions like health planning, research, collaboration with primary care
      providers, and generation of policies and practices, in order to improve the
      quality of life and care of families with PID.

PMID- 28448573
TI  - Correction: Kidney dysfunction and cerebral microbleeds in neurologically healthy
      adults.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0172210.].

PMID- 28448572
TI  - Clonality, virulence determinants, and profiles of resistance of clinical
      Acinetobacter baumannii isolates obtained from a Spanish hospital.
AB  - INTRODUCTION: Acinetobacter baumannii is a nosocomial pathogen that is showing
      increasing rates of carbapenem resistance. Multi-Drug Resistant (MDR)
      International Clones (ICs), associated with certain oxacillinases, are being
      reported globally. This organism also harbors numerous virulence determinants. In
      this study, we aim at characterizing A. baumannii isolated from a Spanish
      hospital in terms of antimicrobial susceptibility, clonality, carbapenemase genes
      harbored, and virulence determinants expressed. MATERIALS AND METHODS: Fifty nine
      clinical bloodstream isolates were obtained from 2009 until 2013. Antimicrobial
      Susceptibility Testing was performed according to the CLSI guidelines. PFGE and
      tri-locus PCR typing were then performed in order to determine local and
      international clonality. PCRs for the detection of common carbapenemases were
      also performed. Production of hemolysis, biofilms, siderophores, surface
      motility, and proteolysis were determined phenotypically. Doubling times for
      selected strains were also calculated. Finally, statistical analysis for
      detecting associations between these factors was conducted. RESULTS AND
      DISCUSSION: Carbapenem non-susceptibility was 84.75%, suggesting the immediate
      need for intervention. PFGE showed the distribution of the majority of the
      isolates among 7 clusters. Although all three ICs were detected, IC II was
      predominant at 71.19%. blaOXA-24-like was the most prevalent carbapenemase
      (62.71%), followed by blaOXA-58-like (13.56%), and blaOXA-23-like (11.86%).
      Strains pertaining to IC II, and those harboring blaOXA-24-like, were positively
      associated with alpha-hemolysis, production of strong biofilms, and siderophore
      production. Harboring blaOXA-23-like and blaOXA-58-like was associated with
      attenuated virulence. These associations suggest that an interplay exists between
      these factors that could be locally exploited. CONCLUSIONS: An alarmingly high
      rate of carbapenem non-susceptibility has been detected in this study. There was
      a predominance of IC II and blaOXA-24-like, and those factors were associated
      with heightened expression of virulence determinants. This association could be
      exploited for modifying treatment regimens and for improving on infection control
      protocols in this hospital.

PMID- 28448571
TI  - Localization of adenovirus morphogenesis players, together with visualization of
      assembly intermediates and failed products, favor a model where assembly and
      packaging occur concurrently at the periphery of the replication center.
AB  - Adenovirus (AdV) morphogenesis is a complex process, many aspects of which remain
      unclear. In particular, it is not settled where in the nucleus assembly and
      packaging occur, and whether these processes occur in a sequential or a concerted
      manner. Here we use immunofluorescence and immunoelectron microscopy (immunoEM)
      to trace packaging factors and structural proteins at late times post infection
      by either wildtype virus or a delayed packaging mutant. We show that
      representatives of all assembly factors are present in the previously recognized
      peripheral replicative zone, which therefore is the AdV assembly factory.
      Assembly intermediates and abortive products observed in this region favor a
      concurrent assembly and packaging model comprising two pathways, one for capsid
      proteins and another one for core components. Only when both pathways are coupled
      by correct interaction between packaging proteins and the genome is the viral
      particle produced. Decoupling generates accumulation of empty capsids and
      unpackaged cores.

PMID- 28448574
TI  - Fusion expression of Occludin extracellular loops and an alpha-helical bundle: A
      new research model for tight junction.
AB  - Tight junctions (TJs) are the outermost structures of intercellular junctions and
      are highly specialized membrane domains involved in many important cellular
      processes. However, most TJ proteins are four-time transmembrane proteins and are
      difficult to express in their correct soluble form, which limits their functional
      study and therapeutic application. Human occludin (OCLN) is a major component of
      TJs and an essential co-receptor for hepatitis C virus (HCV) cell entry. To
      explore expression strategy for recombinant TJ proteins possessing integrated and
      functional extracellular loops, OCLN was here used as a model molecule, and
      several prokaryotic fusion constructs were designed by docking OCLN extracellular
      loops (ECLs) to HIV-1 gp41 NHR and CHR six-helical bundle (6HV1); then their
      biophysical features and anti-HCV activity were evaluated. The proteins were
      successfully expressed and purified in E. coli, and the double-loop constructs
      (D1ECL1S+D2ECL2 as a representative) were found to have more potent HCV
      neutralizing activity than single-loop constructs at non-cytotoxic
      concentrations. Circular dichroism studies indicate that D1ECL1S+D2ECL2 adopt
      stable alpha-helical folds consistent with design. Thermal denaturation assay
      indicated that D1ECL1S+D2ECL2 is highly stable at 80 degrees C (melting
      temperature, Tm, of 89.08 +/- 2.0 degrees C) and comparable in stability to the
      6HV1 scaffold. Moreover, the time-of-addition experiment revealed that
      D1ECL1S+D2ECL2 predominantly functioned during the early stages of HCV entry.
      Taken together, these findings provide a novel strategy for recombinant TJ
      protein expression in vitro, which may shed light on functional and structural
      studies for TJs and may provide a new avenue to drug development.

PMID- 28448575
TI  - Speeding up profiling program's runtime characteristics for workload
      consolidation.
AB  - Workload consolidation is a common method to increase resource utilization of the
      clusters or data centers while still trying to ensure the performance of the
      workloads. In order to get the maximum benefit from workload consolidation, the
      task scheduler has to understand the runtime characteristics of the individual
      program and schedule the programs with less resource conflict onto the same
      server. We propose a set of metrics to comprehensively depict the runtime
      characteristics of programs. The metrics set consists of two types of metrics:
      resource usage and resource sensitivity. The resource sensitivity refers to the
      performance degradation caused by insufficient resources. The resource usage of a
      program is easy to get by common performance analysis tools, but the resource
      sensitivity can not be obtained directly. The simplest and the most intuitive way
      to obtain the resource sensitivity of a program is to run the program in an
      environment with controllable resources and record the performance achieved under
      all possible resource conditions. However, such a process is very much time
      consuming when multiple resources are involved and each resource is controlled in
      fine granularity. In order to obtain the resource sensitivity of a program
      quickly, we propose a method to speed up the resource sensitivity profiling
      process. Our method is realized based on two level profiling acceleration
      strategies. First, taking advantage of the resource usage information, we set up
      the maximum resource usage of the program as the upper bound of the controlled
      resource. In this way, the range of controlling resource levels can be narrowed,
      and the number of experiments can be significantly reduced. Secondly, using a
      prediction model achieved by interpolation, we can reduce the time spent on
      profiling even further because the resource sensitivity in most of the resource
      conditions is obtained by interpolation instead of real program execution. These
      two profiling acceleration strategies have been implemented and applied in
      profiling program runtime characteristics. Our experiment results show that the
      proposed two-level profiling acceleration strategy not only shortens the process
      of profiling, but also guarantees the accuracy of the resource sensitivity. With
      the fast profiling method, the average absolute error of the resource sensitivity
      can be controlled within 0.05.

PMID- 28448577
TI  - Correction: Selective Chemokine Receptor Usage by Central Nervous System Myeloid
      Cells in CCR2-Red Fluorescent Protein Knock-In Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0013693.].

PMID- 28448576
TI  - Management of chronic Hepatitis C at a primary health clinic in the high-burden
      context of Karachi, Pakistan.
AB  - BACKGROUND: The burden of hepatitis C (HCV) infection in Pakistan is among the
      highest in the world, with a reported national HCV prevalence of 6.7% in 2014. In
      specific populations, such as in urban communities in Karachi, the prevalence is
      suspected to be higher. Interferon-free treatment for chronic HCV infection (CHC)
      could allow scale up, simplification and decentralization of treatment to such
      communities. We present an interim analysis over the course of February-December
      2015 of an interferon-free, decentralised CHC programme in the community clinic
      in Machar Colony, Karachi, Pakistan. DESIGN: A retrospective analysis of a
      treatment cohort. RESULTS: There were 1,089 patients included in this analysis.
      Aspartate to platelet ratio index score was used to prioritize patients in terms
      of treatment initiation, with 242 patients placed in high priority for treatment
      and 202 starting treatment as scheduled. 169 patients started HCV treatment with
      Sofosbuvir-Ribavirin regimen according to HCV genotype over the course of 2015:
      of these, 35% had Hemoglobin reductions below 11.0 g/dl during the treatment
      course. Among the 153 patients (85%) with genotype 3 HCV infection, 84% of
      patients achieved sustained virologic response at 12 weeks following treatment
      completion (SVR 12). CONCLUSION: Outcomes of HCV treatment with all oral
      combination in an integrated, decentralized model of care for CHC in a primary
      care setting, using simplified diagnostic and treatment algorithms, are
      comparable to the outcomes achieved in clinical trial settings for Sofosbuvir
      based regimens. Our results suggest the feasibility and the pertinence if
      including interferon-free treatment regimens in the national programme, at both
      provincial and national levels.

PMID- 28448578
TI  - Evolutionary history of Tibetans inferred from whole-genome sequencing.
AB  - The indigenous people of the Tibetan Plateau have been the subject of much recent
      interest because of their unique genetic adaptations to high altitude. Recent
      studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high
      altitude-adaptation and originated in an archaic Denisovan-related population. We
      sequenced the whole-genomes of 27 Tibetans and conducted analyses to infer a
      detailed history of demography and natural selection of this population. We
      detected evidence of population structure between the ancestral Han and Tibetan
      subpopulations as early as 44 to 58 thousand years ago, but with high rates of
      gene flow until approximately 9 thousand years ago. The CMS test ranked EPAS1 and
      EGLN1 as the top two positive selection candidates, and in addition identified
      PTGIS, VDR, and KCTD12 as new candidate genes. The advantageous Tibetan EPAS1
      haplotype shared many variants with the Denisovan genome, with an ancient gene
      tree divergence between the Tibetan and Denisovan haplotypes of about 1 million
      years ago. With the exception of EPAS1, we observed no evidence of positive
      selection on Denisovan-like haplotypes.

PMID- 28448579
TI  - IL-33 receptor ST2 regulates the cognitive impairments associated with
      experimental cerebral malaria.
AB  - Cerebral malaria (CM) is associated with a high mortality rate and long-term
      neurocognitive impairment in survivors. The murine model of experimental cerebral
      malaria (ECM) induced by Plasmodium berghei ANKA (PbA)-infection reproduces
      several of these features. We reported recently increased levels of IL-33 protein
      in brain undergoing ECM and the involvement of IL-33/ST2 pathway in ECM
      development. Here we show that PbA-infection induced early short term and spatial
      memory defects, prior to blood brain barrier (BBB) disruption, in wild-type mice,
      while ST2-deficient mice did not develop cognitive defects. PbA-induced
      neuroinflammation was reduced in ST2-deficient mice with low Ifng, Tnfa, Il1b,
      Il6, CXCL9, CXCL10 and Cd8a expression, associated with an absence of
      neurogenesis defects in hippocampus. PbA-infection triggered a dramatic increase
      of IL-33 expression by oligodendrocytes, through ST2 pathway. In vitro, IL-33/ST2
      pathway induced microglia expression of IL-1beta which in turn stimulated IL-33
      expression by oligodendrocytes. These results highlight the IL-33/ST2 pathway
      ability to orchestrate microglia and oligodendrocytes responses at an early stage
      of PbA-infection, with an amplification loop between IL-1beta and IL-33,
      responsible for an exacerbated neuroinflammation context and associated
      neurological and cognitive defects.

PMID- 28448580
TI  - Sildenafil normalizes bowel transit in preclinical models of constipation.
AB  - Guanylyl cyclase-C (GC-C) agonists increase cGMP levels in the intestinal
      epithelium to promote secretion. This process underlies the utility of exogenous
      GC-C agonists such as linaclotide for the treatment of chronic idiopathic
      constipation (CIC) and irritable bowel syndrome with constipation (IBS-C).
      Because GC-C agonists have limited use in pediatric patients, there is a need for
      alternative cGMP-elevating agents that are effective in the intestine. The
      present study aimed to determine whether the PDE-5 inhibitor sildenafil has
      similar effects as linaclotide on preclinical models of constipation. Oral
      administration of sildenafil caused increased cGMP levels in mouse intestinal
      epithelium demonstrating that blocking cGMP-breakdown is an alternative approach
      to increase cGMP in the gut. Both linaclotide and sildenafil reduced
      proliferation and increased differentiation in colon mucosa, indicating common
      target pathways. The homeostatic effects of cGMP required gut turnover since
      maximal effects were observed after 3 days of treatment. Neither linaclotide nor
      sildenafil treatment affected intestinal transit or water content of fecal
      pellets in healthy mice. To test the effectiveness of cGMP elevation in a
      functional motility disorder model, mice were treated with dextran sulfate sodium
      (DSS) to induce colitis and were allowed to recover for several weeks. The
      recovered animals exhibited slower transit, but increased fecal water content. An
      acute dose of sildenafil was able to normalize transit and fecal water content in
      the DSS-recovery animal model, and also in loperamide-induced constipation. The
      higher fecal water content in the recovered animals was due to a compromised
      epithelial barrier, which was normalized by sildenafil treatment. Taken together
      our results show that sildenafil can have similar effects as linaclotide on the
      intestine, and may have therapeutic benefit to patients with CIC, IBS-C, and post
      infectious IBS.

PMID- 28448581
TI  - The performance of BD FACSPrestoTM for CD4 T-cell count, CD4% and hemoglobin
      concentration test in Ethiopia.
AB  - INTRODUCTION: In Ethiopia, CD4+ T-cell counting is still required for all
      patients at baseline before antiretroviral therapy (ART) and to determine
      eligibility and follow-up of opportunistic infection prophylaxis. However, access
      to CD4+ T cell count in rural health facilities remains a major challenge in
      Ethiopia like other resource-limited settings. METHODOLOGY: Both capillary and
      venous blood was drawn from each of 325 study participant recruited in Addis
      Ababa and surroundings. The CD4+ T-cell count, CD4%, and hemoglobin (Hgb) were
      tested at one of the four study health facilities using capillary blood and BD
      FACSPrestoTM device. These tests were also done at the national HIV reference
      laboratory, using venous blood with BD FACSCaliburTM, Sysmex XT-1800iTM, and BD
      FACSPrestoTM. RESULTS: BD FACSPrestoTM had an absolute mean bias of -13.3
      cells/ul (-2.99%) and 28.3 cells/MUl (6.4%) using venous and capillary blood,
      respectively, compared with BD FACSCaliburTM. The absolute CD4 assay on the BD
      FACSPrestoTM had a regression coefficient (R2) of 0.87 and 0.92 using capillary
      blood and venous blood samples, respectively, compared with BD FACSCaliburTM. The
      percentage similarity of the BD FACSPrestoTM using capillary and venous blood was
      105.2% and 99.3%, respectively. The sensitivity of the FACSPrestoTM using
      threshold of 500 cells/MUl for ART eligibility using capillary and venous blood
      was 87.9 and 94.3%, while the specificity was 91.4 and 83.8%, respectively.
      Furthermore, the BD FACSPrestoTM had an absolute mean bias of -0.2 dl/MUl (0.0%)
      (95% LOA: -1.7, 1.3) and -0.59 dl/MUl (0.1%) (95% LOA: -1.49, 0.31) for Hgb using
      capillary and venous blood compared with the Sysmex XT-1800iTM, respectively.
      CONCLUSION: Our results showed acceptable agreement between the BD FACSPrestoTM
      and BD FACSCaliburTM for CD4+ T-cell counting and CD4%; and between the BD
      FACSPrestoTM and Sysmex XT-1800iTMfor measuring Hgb concentration.

PMID- 28448582
TI  - Comparison of multiple obesity indices for cardiovascular disease risk
      classification in South Asian adults: The CARRS Study.
AB  - BACKGROUND: We comparatively assessed the performance of six simple obesity
      indices to identify adults with cardiovascular disease (CVD) risk factors in a
      diverse and contemporary South Asian population. METHODS: 8,892 participants aged
      20-60 years in 2010-2011 were analyzed. Six obesity indices were examined: body
      mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), waist-hip
      ratio (WHR), log of the sum of triceps and subscapular skin fold thickness (LTS),
      and percent body fat derived from bioelectric impedance analysis (BIA). We
      estimated models with obesity indices specified as deciles and as continuous
      linear variables to predict prevalent hypertension, diabetes, and high
      cholesterol and report associations (prevalence ratios, PRs), discrimination
      (area-under-the-curve, AUCs), and calibration (index chi2). We also examined a
      composite unhealthy cardiovascular profile score summarizing glucose, lipids, and
      blood pressure. RESULTS: No single obesity index consistently performed
      statistically significantly better than the others across the outcome models.
      Based on point estimates, WHtR trended towards best performance in classifying
      diabetes (PR = 1.58 [1.45-1.72], AUC = 0.77, men; PR = 1.59 [1.47-1.71], AUC =
      0.80, women) and hypertension (PR = 1.34 [1.26,1.42], AUC = 0.70, men; PR = 1.41
      [1.33,1.50], AUC = 0.78, women). WC (mean difference = 0.24 SD [0.21-0.27]) and
      WHtR (mean difference = 0.24 SD [0.21,0.28]) had the strongest associations with
      the composite unhealthy cardiovascular profile score in women but not in men.
      CONCLUSIONS: WC and WHtR were the most useful indices for identifying South Asian
      adults with prevalent diabetes and hypertension. Collection of waist
      circumference data in South Asian health surveys will be informative for
      population-based CVD surveillance efforts.

PMID- 28448583
TI  - Characterization of the fecal microbiome during neonatal and early pediatric
      development in puppies.
AB  - Limited information is available describing the development of the neonatal fecal
      microbiome in dogs. Feces from puppies were collected at 2, 21, 42, and 56 days
      after birth. Feces were also collected from the puppies' mothers at a single time
      point within 24 hours after parturition. DNA was extracted from fecal samples and
      454-pyrosequencing was used to profile 16S rRNA genes. Species richness continued
      to increase significantly from 2 days of age until 42 days of age in puppies.
      Furthermore, microbial communities clustered separately from each other at 2, 21,
      and 42 days of age. The microbial communities belonging to dams clustered
      separately from that of puppies at any given time point. Major phylogenetic
      changes were noted at all taxonomic levels with the most profound changes being a
      shift from primarily Firmicutes in puppies at 2 days of age to a co-dominance of
      Bacteroidetes, Fusobacteria, and Firmicutes by 21 days of age. Further studies
      are needed to elucidate the relationship between puppy microbiota development,
      physiological growth, neonatal survival, and morbidity.

PMID- 28448584
TI  - Sarcopenia in patients with chronic kidney disease not yet on dialysis: Analysis
      of the prevalence and associated factors.
AB  - INTRODUCTION: Sarcopenia is a chronic condition that is associated with aging and
      characterized by a reduction of muscle mass, strength, and function. Sarcopenia
      is prevalent in patients with chronic kidney disease (CKD) and associated with
      increased morbidity and mortality, as well as cardiovascular complications.
      OBJECTIVES: To investigate the prevalence of sarcopenia in patients with CKD not
      yet on dialysis and its correlation with clinical and laboratory variables and
      inflammatory markers. METHODS: A total of 100 patients of both sexes aged over 18
      were evaluated. Sarcopenia was defined using the criteria of the European Working
      Group on Sarcopenia in Older People (EWGSOP) and of the Foundation for the
      National Institutes of Health (FNIH) Sarcopenia Project. Sociodemographic and
      clinical data, activities of daily living, functional capacity, and physical
      activity were also evaluated. Inflammation was assessed by the serum levels of
      high-sensitivity C-reactive protein (hsCRP) and interleukin (IL) 4 and 6.
      RESULTS: The prevalence of sarcopenia was 11.9% and 28.7% using the EWGSOP and
      FNIH criteria, respectively. Sarcopenia was more prevalent in the more advanced
      stages of CKD (34.5% in stages 2 and 3A; and 65.5% in stages 3B, 4, and 5) and
      associated with worse performance in activities of daily living (p = 0.049),
      lower walking speeds (p < 0.001), and higher body mass indexes (BMIs) (p = 0.001)
      in the non-adjusted model. In addition, patients with sarcopenia had lower
      functional capacity (p = 0.012) and higher prevalence of physical inactivity (p =
      0.041) compared with patients without sarcopenia. After adjustment for
      confounding variables, sarcopenia was still significantly correlated with walking
      speed (p = 0.004) and BMI (p = 0.002). HsCRP levels were inversely correlated
      with appendicular lean mass adjusted for BMI (p = 0.007) and were also positively
      associated with BMI (p = 0.001). IL4 levels were positively correlated with
      walking speed (p = 0.007) and lean mass in the lower limbs (p = 0.022).
      CONCLUSIONS: Sarcopenia is common in patients with CKD, particularly in the most
      advanced stages of the disease. We observed an association between the levels of
      inflammatory markers and peripheral lean body mass, physical performance, and
      BMI. This association between sarcopenia and modifiable factors highlights the
      importance of early diagnosis and the implementation of therapeutic measures to
      minimize adverse outcomes in patients with CKD not yet on dialysis.

PMID- 28448585
TI  - Impact of temperature and soil type on Mycobacterium bovis survival in the
      environment.
AB  - Mycobacterium bovis, the causative agent of the bovine tuberculosis (bTB), mainly
      affects cattle, its natural reservoir, but also a wide range of domestic and wild
      mammals. Besides direct transmission via contaminated aerosols, indirect
      transmission of the M. bovis between wildlife and livestock might occur by
      inhalation or ingestion of environmental substrates contaminated through infected
      animal shedding. We monitored the survival of M. bovis in two soil samples chosen
      for their contrasted physical and-chemical properties (i.e. pH, clay content).
      The population of M. bovis spiked in sterile soils was enumerated by a culture
      based method after 14, 30, 60, 90, 120 and 150 days of incubation at 4 degrees C
      and 22 degrees C. A qPCR based assay targeting the IS1561' locus was also
      performed to monitor M. bovis in both sterile and biotic spiked soils. The
      analysis of survival profiles using culture-based method showed that M. bovis
      survived longer at lower temperature (4 degrees C versus 22 degrees C) whereas
      the impact of soil characteristics on M. bovis persistence was not obvious.
      Furthermore, qPCR-based assay detected M. bovis for a longer period of time than
      the culture based method with higher gene copy numbers observed in sterile soils
      than in biotic ones. Impact of soil type on M. bovis persistence need to be
      deepened in order to fill the gap of knowledge concerning indirect transmission
      of the disease.

PMID- 28448586
TI  - Teaching systems thinking to 4th and 5th graders using Environmental Dashboard
      display technology.
AB  - Tackling complex environmental challenges requires the capacity to understand how
      relationships and interactions between parts result in dynamic behavior of whole
      systems. There has been convincing research that these "systems thinking" skills
      can be learned. However, there is little research on methods for teaching these
      skills to children or assessing their impact. The Environmental Dashboard is a
      technology that uses "sociotechnical" feedback-information feedback designed to
      affect thought and behavior. Environmental Dashboard (ED) combines real-time
      information on community resource use with images and words that reflect pro
      environmental actions of community members. Prior research indicates that ED
      supports the development of systems thinking in adults. To assess its impact on
      children, the technology was installed in a primary school and children were
      passively exposed to ED displays. This resulted in no measurable impact on
      systems thinking skills. The next stage of this research examined the impact of
      actively integrating ED into lessons on electricity in 4th and 5th grade. This
      active integration enhanced both content-related systems thinking skills and
      content retention.

PMID- 28448587
TI  - Collection of cell-free DNA for genomic analysis of solid tumors in a clinical
      laboratory setting.
AB  - The breadth of diagnostic procedures that utilize cell free DNA (cfDNA) from
      human plasma has increased dramatically in recent years. Here, we confirm that
      tumor-derived cfDNA fragments are similar in size distribution to cfDNA derived
      from normal tissues. Therefore, collection procedures optimized with healthy
      donor specimens are likely to be applicable to the diagnosis and monitoring of
      many different cancer types. We verify that the distribution and DNA sequences of
      fragmentation sites in cfDNA from both normal-germline and tumor-derived cfDNA
      are non-random. A broad survey of cfDNA from healthy donors suggests that average
      individuals possess ~6 ng of cfDNA per mL of plasma. Importantly, the cfDNA
      present in plasma samples that were initially collected as whole blood in K2-EDTA
      tubes and subsequently processed by centrifugation is stable for several days at
      ambient temperatures. This observation has the potential to significantly reduce
      the cost and logistical complexity of shipping clinical samples from the site of
      collection to centers proficient in diagnostic analysis. Finally, plasma samples
      collected with high-volume plasma collection devices possess abundant quantities
      of cfDNA. Since the quantity of analyzed cfDNA is directly proportional to
      sensitivity of diagnostic assays, this method of plasma collection, where
      available, could enable highly sensitive post-treatment disease monitoring and
      early detection of cancer in at-risk individuals.

PMID- 28448588
TI  - Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling
      post-myocardial infarction.
AB  - Cell therapy repair strategies using adult mesenchymal stromal cells have shown
      promising evidence to prevent cardiac deterioration in rodents even in the
      absence of robust differentiation of the cells into cardiomyocytes. We tested
      whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells
      (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI)
      receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta
      blockers similarly to patients. Female pigs were subjected to MI induction by
      sponge permanent occlusion of left circumflex coronary artery (LCx) generating
      approximately 10% of injured LV area with minimum hemodynamic impact. We assessed
      tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using
      commercial microbubbles before and following pASCs treatment. Four weeks after
      the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1,
      2 and 4x106 cells/Kg BW) into the myocardium. The highest dose of pASCs increased
      myocardial vessel number and blood flow in the border (56% and 3.7-fold,
      respectively) and in the remote area (54% and 3.9-fold, respectively) while the
      non-perfused scar area decreased (up to 38%). We also found an increase of
      immature collagen fibers, although the increase in total tissue collagen and
      types I and III was similar in all groups. Our results provide evidence that
      pASCs-induced stimulation of tissue perfusion and accumulation of immature
      collagen fibers attenuates adverse remodeling post-MI beyond the normal
      beneficial effects associated with ACE inhibition and beta-blockade.

PMID- 28448589
TI  - Morpho-physiological analysis of tolerance to aluminum toxicity in rice varieties
      of North East India.
AB  - Aluminum (Al) is the third most abundant metal in earth crust, whose chemical
      form is mainly dependent on soil pH. The most toxic form of Al with respect to
      plants is Al3+, which exists in soil pH <5. Acidic soil significantly limits crop
      production mainly due to Al3+ toxicity worldwide, impacting approximately 50% of
      the world's arable land (in North-Eastern India 80% soil are acidic). Al3+
      toxicity in plants ensues root growth inhibition leading to less nutrient and
      water uptake impacting crop productivity as a whole. Rice is one of the chief
      grains which constitutes the staple food of two-third of the world population
      including India and is not untouched by Al3+ toxicity. Al contamination is a
      critical constraint to plant production in agricultural soils of North East
      India. 24 indigenous Indica rice varieties (including Badshahbhog as tolerant
      check and Mashuri as sensitive check) were screened for Al stress tolerance in
      hydroponic plant growth system. Results show marked difference in growth
      parameters (relative growth rate, Root tolerance index, fresh and dry weight of
      root) of rice seedlings due to Al (100 MUM) toxicity. Al3+ uptake and lipid
      peroxidation level also increased concomitantly under Al treatment. Histochemical
      assay were also performed to elucidate uptake of aluminum, loss of membrane
      integrity and lipid peroxidation, which were found to be more in sensitive
      genotypes at higher Al concentration. This study revealed that aluminum toxicity
      is a serious harmful problem for rice crop productivity in acid soil. Based on
      various parameters studied it's concluded that Disang is a comparatively tolerant
      variety whereas Joymati a sensitive variety. Western blot hybridization further
      strengthened the claim, as it demonstrated more accumulation of Glutathione
      reductase (GR) protein in Disang rice variety than Joymati under stressed
      condition. This study also observed that the emergence of lethal toxic symptoms
      occurs only after 48h irrespective of the dose used in the study.

PMID- 28448590
TI  - Significant changes in circulating microRNA by dietary supplementation of
      selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a
      prospective randomized double-blind placebo-controlled trial among elderly
      Swedish citizens.
AB  - BACKGROUND: Selenium and coenzyme Q10 is essential for important cellular
      functions. A low selenium intake is reported from many European countries, and
      the endogenous coenzyme Q10 production is decreasing in the body with increasing
      age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced
      cardiovascular mortality and reduced levels of markers of inflammation. However,
      microRNA analyses could give important information on the mechanisms behind the
      clinical effects of supplementation. METHODS: Out of the 443 healthy elderly
      participants that were given supplementation with 200 MUg Se/day as organic
      selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4
      years, 25 participants from each group were randomized and evaluated regarding
      levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR
      analysis were performed. Volcano- and principal component analyses (PCA)-plots
      were used to illustrate the differences in microRNA expression between the
      intervention, and the placebo groups. Serum selenium concentrations were measured
      before intervention. FINDINGS: On average 145 different microRNAs out of 172 were
      detected per sample. In the PCA plots two clusters could be identified indicating
      significant difference in microRNA expression between the two groups. The pre
      treatment expression of the microRNAs did not differ between active treatment and
      the placebo groups. When comparing the post-treatment microRNAs in the active and
      the placebo groups, 70 microRNAs exhibited significant differences in expression,
      also after adjustment for multiple measurements. For the 20 microRNAs with the
      greatest difference in expression the difference was up to more than 4 fold and
      with a P-value that were less than 4.4e-8. CONCLUSIONS: Significant differences
      were found in expression of more than 100 different microRNAs with up to 4 fold
      differences as a result of the intervention of selenium and coenzyme Q10
      combined. The changes in microRNA could be a part of mechanisms underlying the
      clinical effects earlier reported that reduced cardiovascular mortality, gave
      better cardiac function, and showed less signs of inflammation and oxdative
      stress following the intervention. However, more research is needed to understand
      biological mechanisms of the protective effects of selenium and Q10
      supplementation.

PMID- 28448591
TI  - Strain-based diffusion solver for realistic representation of diffusion front in
      physical reactions.
AB  - When simulating fluids, such as water or fire, interacting with solids, it is a
      challenging problem to represent details of diffusion front in physical reaction.
      Previous approaches commonly use isotropic or anisotropic diffusion to model the
      transport of a quantity through a medium or long interface. We have identified
      unrealistic monotonous patterns with previous approaches and therefore, propose
      to extend these approaches by integrating the deformation of the material with
      the diffusion process. Specifically, stretching deformation represented by strain
      is incorporated in a divergence-constrained diffusion model. A novel diffusion
      model is introduced to increase the global rate at which the solid acquires
      relevant quantities, such as heat or saturation. This ensures that the equations
      describing fluid flow are linked to the change of solid geometry, and also
      satisfy the divergence-free condition. Experiments show that our method produces
      convincing results.

PMID- 28448592
TI  - Blood type, ABO genetic variants, and ovarian cancer survival.
AB  - OBJECTIVE: Blood type A and the A1 allele have been associated with increased
      ovarian cancer risk. With only two small studies published to date, evidence for
      an association between ABO blood type and ovarian cancer survival is limited.
      METHODS: We conducted a retrospective cohort study of Tumor Registry confirmed
      ovarian cancer cases from the Vanderbilt University Medical Center with blood
      type from linked laboratory reports and ABO variants from linked Illumina Exome
      BeadChip data. Associations with overall survival (OS) were quantified by hazard
      ratios (HR) and confidence intervals (CI) from proportional hazards regression
      models; covariates included age, race, stage, grade, histologic subtype, and year
      of diagnosis. RESULTS: ABO phenotype (N = 694) and/or genotype (N = 154) data
      were available for 713 predominantly Caucasian (89.3%) cases. In multivariable
      models, blood type A had significantly better OS compared to either O (HR: 0.75,
      95% CI: 0.60-0.93) or all non-A (HR: 0.77, 95% CI: 0.63-0.94) cases. Similarly,
      missense rs1053878 minor allele carriers (A2) had better OS (HR: 0.50, 95% CI:
      0.25-0.99). Among Caucasians, this phenotype association was strengthened, but
      the genotype association was attenuated; instead, four variants sharing moderate
      linkage disequilibrium with the O variant were associated with better OS (HR:
      0.62, 95% CI: 0.39-0.99) in unadjusted models. CONCLUSIONS: Blood type A was
      significantly associated with longer ovarian cancer survival in the largest such
      study to date. This finding was supported by genetic analysis, which implicated
      the A2 allele, although O related variants also had suggestive associations.
      Further research on ABO and ovarian cancer survival is warranted.

PMID- 28448593
TI  - Benzodiazepines, Z-drugs and the risk of hip fracture: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Hip fractures in the older person lead to an increased risk of
      mortality, poorer quality of life and increased morbidity. Benzodiazepine (BNZ)
      use is associated with increased hip fracture rate, consequently Z-drugs are fast
      becoming the physician's hypnotic prescription of choice yet data on their use is
      limited. We compared the risk of hip fracture associated with Z-drugs and BNZ
      medications, respectively, and examined if this risk varied with longer-term use.
      METHODS AND FINDINGS: We carried out a systematic review of the literature and
      meta-analysis. MEDLINE and SCOPUS were searched to identify studies involving BNZ
      or Z-drugs and the risk of hip fracture up to May 2015. Each included study was
      quality-assessed. A pooled relative risk of hip fracture was calculated using the
      generic inverse variance method, with a random effects model, with the length of
      hypnotic usage as a subgroup. Both BNZ, and Z-drug use respectively, were
      significantly associated with an increased risk of hip fracture (RR = 1.52, 95%
      CI 1.37-1.68; and RR = 1.90, 95% CI 1.68-2.13). Short-term use of BNZ and Z-drugs
      respectively, was also associated with the greatest risk of hip fracture (RR =
      2.40, 95% CI 1.88-3.05 and RR = 2.39, 95% CI 1.74-3.29). CONCLUSIONS: There is
      strong evidence that both BNZ and Z-drugs are associated with an increased risk
      of hip fracture in the older person, and there is little difference between their
      respective risks. Patients newly prescribed these medicines are at the greatest
      risk of hip fracture. Clinicians and policy makers need to consider the increased
      risk of fallings and hip fracture particularly amongst new users of these
      medications.

PMID- 28448594
TI  - Novel, in-natural-infection subdominant HIV-1 CD8+ T-cell epitopes revealed in
      human recipients of conserved-region T-cell vaccines.
AB  - BACKGROUND: Fine definition of targeted CD8+ T-cell epitopes and their human
      leucocyte antigen (HLA) class I restriction informs iterative improvements of HIV
      1 T-cell vaccine designs and may predict early vaccine success or failure. Here,
      lymphocytes from volunteers, who had received candidate HIVconsv vaccines
      expressing conserved sub-protein regions of HIV-1, were used to define the
      optimum-length target epitopes and their HLA restriction. In HIV-1-positive
      patients, CD8+ T-cell responses predominantly recognize immunodominant, but
      hypervariable and therefore less protective epitopes. The less variable, more
      protective epitopes in conserved regions are typically subdominant. Therefore,
      induction of strong responses to conserved regions by vaccination provides an
      opportunity to discover novel important epitopes. METHODS: Cryopreserved
      lymphocytes from vaccine recipients were expanded by stimulation with 15-mer
      responder peptides for 10 days to establish short term-cell-line (STCL) effector
      cells. These were subjected to intracellular cytokine staining using serially
      truncated peptides and peptide-pulsed 721.221 cells expressing individual HLA
      class I alleles to define minimal epitope length and HLA restriction by
      stimulation of IFN-gamma and TNF-alpha production and surface expression of
      CD107a. RESULTS: Using lymphocyte samples of 12 vaccine recipients, we defined 14
      previously unreported optimal CD8+ T-cell HIV-1 epitopes and their four-digit HLA
      allele restriction (6 HLA-A, 7 HLA-B and 1 HLA-C alleles). Further 13 novel
      targets with incomplete information were revealed. CONCLUSIONS: The high rate of
      discovery of novel CD8+ T-cell effector epitopes warrants further epitope mining
      in recipients of the conserved-region vaccines in other populations and informs
      development of HIV-1/AIDS vaccines. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01151319.

PMID- 28448595
TI  - Hantavirus surveillance and genetic diversity targeting small mammals at Camp
      Humphreys, a US military installation and new expansion site, Republic of Korea.
AB  - Small mammal surveillance was conducted (2008-2010, 2012) at Camp (Cp) Humphreys,
      a US Army installation and new expansion site, Republic of Korea (ROK), to
      identify hemorrhagic fever with renal syndrome health threats to US
      military/civilian populations during its ongoing expansion phase. Small mammals
      were collected using Sherman live capture traps and transported to Korea
      University where they were euthanized, tissues removed, and assayed to determine
      hantavirus IgG antibody-positive and hantavirus-positive rates by RT-PCR. A total
      of 2,364 small mammals were captured over 11,300 trap nights (capture rate =
      20.92%). Apodemus agrarius was the most commonly collected (76.65%), with capture
      rates of 9.62% and 21.70% for Cp Humphreys and the expansion site, respectively.
      Overall, Hantaan virus (HTNV) IgG antibody-positive (Ab+) rate for A. agrarius
      was 2.15% (39/1,812). A total of 5.43% (10/184) Crocidura lasiura, 0.79% (2/254)
      Microtus fortis and 2.44% (1/41) Micromys minutus were serologically IgG Ab+ for
      hantaviruses. HTNV-specific RT-PCR demonstrated that 28.2% (11/39) HTNV Ab+ A.
      agrarius harbored the 328-nt sequence of the GC glycoprotein-encoding M segment
      of HTNV. Among them, the whole genome sequences of 3 HTNV strains were obtained
      by conventional RT-PCR and Rapid Amplification cDNA Ends PCR. Phylogenetic
      analyses of the HTNV strains from Cp Humphreys and the expansion site,
      Pyeongtaek, show a greater diversity of rodent-borne hantaviruses compared to
      HTNV previously identified in Gyeonggi province of the ROK. Thus, this study
      provides significant insights for raising HFRS threat awareness, analysis, and
      risk reduction strategies in southern Gyeonggi province.

PMID- 28448596
TI  - Prevalence and complications of hypouricemia in a general population: A large
      scale cross-sectional study in Japan.
AB  - BACKGROUNDS: Hypouricemia was reported as a risk factor for exercise-induced
      acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney
      diseases among hypouricemic subjects has not been evaluated. This study was
      conducted to clarify the prevalence of hypouricemia and the association of
      hypouricemia with kidney diseases by using a large-scale Japanese population
      data. METHODS: This study is a retrospective cross-sectional study at the Center
      for Preventive Medicine, St. Luke's International Hospital, Tokyo, Japan, and
      Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143
      Japanese subjects at the center in St. Luke's International Hospital, Tokyo, and
      4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular
      health check-up between January 2004 and June 2010. We defined hypouricemia as
      serum uric acid level of <=2.0 mg/dL. We checked the medical history of all the
      study subjects and compared the rates of complications including urinary stones
      and kidney diseases among those with or without hypouricemia. RESULTS: The
      prevalence of hypouricemia was 0.19% in St. Luke's International Hospital, Tokyo,
      and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of hypouricemia in
      women was larger than that in men both in Tokyo (0.31% vs 0.068%, p<0.001) and in
      Yonago (1.237% vs 0.318%, p<0.001). Among 172 hypouricemic subjects (30 men), the
      rates of previous urinary stones and kidney diseases (including
      nephritis/nephrosis) were 1.2% (3.3% men, 0.7% women) and 2.3% (10% men, 0.7%
      women), respectively. Hypouricemic men had a 9-fold higher rate of previously
      having kidney diseases compared to non-hypouricemic men (p<0.001). However, the
      rates of other diseases including urinary stones were not significantly different
      between the two groups. CONCLUSIONS: Hypouricemia was associated with a history
      of kidney disease especially in men.

PMID- 28448597
TI  - Reconstructing grassland fire history using sedimentary charcoal: Considering
      count, size and shape.
AB  - Fire is a key Earth system process, with 80% of annual fire activity taking place
      in grassland areas. However, past fire regimes in grassland systems have been
      difficult to quantify due to challenges in interpreting the charcoal signal in
      depositional environments. To improve reconstructions of grassland fire regimes,
      it is essential to assess two key traits: (1) charcoal count, and (2) charcoal
      shape. In this study, we quantified the number of charcoal pieces in 51 sediment
      samples of ponds in the Great Plains and tested its relevance as a proxy for the
      fire regime by examining 13 potential factors influencing charcoal count,
      including various fire regime components (e.g. the fire frequency, the area
      burned, and the fire season), vegetation cover and pollen assemblages, and
      climate variables. We also quantified the width to length (W:L) ratio of charcoal
      particles, to assess its utility as a proxy of fuel types in grassland
      environments by direct comparison with vegetation cover and pollen assemblages.
      Our first conclusion is that charcoal particles produced by grassland fires are
      smaller than those produced by forest fires. Thus, a mesh size of 120MUm as used
      in forested environments is too large for grassland ecosystems. We recommend
      counting all charcoal particles over 60MUm in grasslands and mixed grass-forest
      environments to increase the number of samples with useful data. Second, a W:L
      ratio of 0.5 or smaller appears to be an indicator for fuel types, when
      vegetation surrounding the site is before composed of at least 40% grassland
      vegetation. Third, the area burned within 1060m of the depositional environments
      explained both the count and the area of charcoal particles. Therefore, changes
      in charcoal count or charcoal area through time indicate a change in area burned.
      The fire regimes of grassland systems, including both human and climatic
      influences on fire behavior, can be characterized by long-term charcoal records.

PMID- 28448598
TI  - A low-volume polyethylene glycol solution was associated with an increased
      suboptimal bowel preparation rate but had similar recommendations for an early
      repeat colonoscopy, procedure times, and adenoma detection rates.
AB  - BACKGROUND/AIMS: Low-volume polyethylene glycol (PEG) bowel preparations are
      better tolerated by patients than high-volume preparations and may achieve
      similar preparation quality. However, there is little data comparing their
      effects on a recommendation for an early repeat colonoscopy (because of a
      suboptimal preparation), procedure times, adenoma detection rate (ADR), and
      advanced adenoma detection rate (AADR). METHODS: This is a retrospective cohort
      study of outpatient colonoscopies performed during a one-year period at a single
      academic medical center in which low-volume MoviPrep(r) (n = 1841) or high-volume
      Colyte(r) (n = 1337) was used. All preparations were split-dosed. Appropriate
      covariates were included in regression models assessing suboptimal preparation
      quality (fair, poor, or inadequate), procedure times, recommendation for an early
      repeat colonoscopy, ADR, and AADR. RESULTS: MoviPrep(r) was associated with an
      increase in having a suboptimal bowel preparation (OR 1.36; 95% CI: 1.06-1.76),
      but it was not associated with differences in insertion (p = 0.43), withdrawal (p
      = 0.22), or total procedure times (p = 0.10). The adjusted percentage with a
      suboptimal preparation was 11.7% for patients using MoviPrep(r) and 8.8% for
      patients using Colyte(r). MoviPrep(r) was not associated with a significant
      difference in overall ADR (OR 0.93; 95% CI: 0.78-1.11), AADR (OR 1.18; 95% CI:
      0.87-1.62), or recommendation for early repeat colonoscopy (OR 1.16; 95% CI: 0.72
      1.88). CONCLUSIONS: MoviPrep(r) was associated with a small absolute increase in
      having a suboptimal preparation, but did not affect recommendations for an early
      repeat colonoscopy, procedure times, or adenoma detection rates. Mechanisms to
      reduce financial barriers limiting low-volume preparations should be considered
      because of their favorable tolerability profile.

PMID- 28448599
TI  - Simulation of the dynamics of primary immunodeficiencies in CD4+ T-cells.
AB  - Primary immunodeficiencies (PIDs) form a large and heterogeneous group of mainly
      rare disorders that affect the immune system. T-cell deficiencies account for
      about one-tenth of PIDs, most of them being monogenic. Apart from genetic and
      clinical information, lots of other data are available for PID proteins and
      genes, including functions and interactions. Thus, it is possible to perform
      systems biology studies on the effects of PIDs on T-cell physiology and response.
      To achieve this, we reconstructed a T-cell network model based on literature
      mining and TPPIN, a previously published core T-cell network, and performed semi
      quantitative dynamic network simulations on both normal and T-cell PID failure
      modes. The results for several loss-of-function PID simulations correspond to
      results of previously reported molecular studies. The simulations for TCR PTPRC,
      LCK, ZAP70 and ITK indicate profound changes to numerous proteins in the network.
      Significant effects were observed also in the BCL10, CARD11, MALT1, NEMO, IKKB
      and MAP3K14 simulations. No major effects were observed for PIDs that are caused
      by constitutively active proteins. The T-cell model facilitates the understanding
      of the underlying dynamics of PID disease processes. The approach confirms
      previous knowledge about T-cell signaling network and indicates several new
      important proteins that may be of interest when developing novel diagnosis and
      therapies to treat immunological defects.

PMID- 28448600
TI  - MSCs feeder layers induce SMG self-organization and branching morphogenesis.
AB  - Dysfunction of salivary glands leads to several oral health problems, including
      dental caries, mastication and swallowing dysfunctions and multiple oral
      infections. Conventional treatments for such condition fell short of providing
      satisfying therapeutic results. Recent advances in organ regeneration therapy
      which utilize tissue stem cells to fabricate bioengineered 3D organ buds, have
      introduced a promising therapeutic tool for full functional organ regeneration.
      However, finding a sustainable and easily accessible cell source for such
      approaches is still challenging, especially in case of severely atrophied tissues
      such as irradiated salivary glands. In response to this, we hypothesized that
      bone marrow derived mesenchymal stem cells (MSCs) could be used as feeder cells
      to induce salivary epithelial tissues/cells branching. Indeed, in 2D cultures,
      MSCs supported branching of embryonic submandibular salivary gland (SMG)
      epithelium. Interestingly, this enhancing effect was dependent on the initial
      number of MSC feeder cells. In addition, MSCs supported the self-assembly of SMG
      epithelial progenitor cells into well-patterned and branched 3D salivary
      organoids. Therefore, these findings propose MSCs as a valuable candidate cell
      source for induced SMG epithelial branching, which can potentially be applied in
      future methods for SMG regeneration approaches.

PMID- 28448601
TI  - Determinants of coronary flow reserve in non-diabetic patients with chest pain
      without myocardial perfusion defects.
AB  - BACKGROUND: Microvascular dysfunction could be responsible for chest pain in
      patients without myocardial perfusion defects. We evaluated microvascular
      function using ultrasound-assessed coronary flow reserve (CFR) in patients with
      chest pain and normal myocardial perfusion scintigram. Secondly, we investigated
      association between cardiovascular parameters and decreased CFR in a sex specific
      manner. METHODS: A total of 202 (128 women) non-diabetic patients with chest pain
      and suspected myocardial ischemia, but without myocardial perfusion defects on
      myocardial perfusion scintigram, were enrolled and underwent CFR examination and
      blood sampling. All patients were followed-up for cardiovascular events. We used
      a supervised principal component analysis including 66 variables such as clinical
      parameters, ongoing medication, coronary artery disease history, lipids,
      metabolic parameters, inflammatory and other cardiovascular parameters. RESULTS:
      During a median follow-up time of 5.4 years, 25 cardiovascular events occurred;
      (men;18, women;7). Average CFR of the study cohort was 2.7+/-1.2 and 14% showed
      impaired CFR<2.0. In an adjusted Cox regression analysis, CFR<2.0 independently
      predicted event-free survival (HR:2.5, p = 0.033). In the supervised principal
      component analysis high insulin resistance assessed by Homeostatic model
      assessment for insulin resistance was the strongest biochemical marker associated
      with decreased CFR. Interestingly, upon sex specific multivariable linear
      regression analysis, the association was only significant in men (beta = -0.132,
      p = 0.041) while systolic blood pressure remained an independent predictor in
      women (beta = -0.009, p = 0.011). CONCLUSIONS: In non-diabetic patients with
      chest pain without myocardial perfusion defects, low CFR has prognostic value for
      future cardiovascular events. Insulin resistance appears to be a marker for
      decreased CFR in men. Indeed, in the context of contribution of traditional risk
      factors in this patient population, the value of systolic blood pressure seems to
      be important in the women.

PMID- 28448602
TI  - Clinical presentation and management of stable coronary artery disease in
      Austria.
AB  - BACKGROUND: Cardiovascular disease is the main cause of death in Austria.
      However, no systematic information exists regarding characteristics and
      treatments of contemporary patients with stable coronary artery disease (CAD) in
      Austria. We assembled two retrospective physicians' databases to describe
      demographics, clinical profiles, and therapeutic strategies in patients with
      stable CAD. In addition, we compared patient profiles of secondary care
      internists and hospital-based cardiologists with those of general practitioners
      in a primary care setting outside of hospital. METHODS: The study population was
      identified from retrospective chart review of 1020 patients from 106 primary care
      physicians in Austria (ProCor II registry), and was merged with a previous
      similar database of 1280 patients under secondary care (ProCor I registry) to
      yield a total patient number of 2300. RESULTS: Female patients with stable CAD
      were older, had more angina and/or heart failure symptoms, and more depression
      than males. Female gender, type 2 diabetes mellitus, higher CCS class and
      asthma/COPD were predictors of elevated heart rate, while previous coronary
      events/revascularization predicted a lower heart rate in multivariate analysis.
      There were no significant differences with regard to characteristics and
      management of patients of general practitioners in the primary care setting
      versus internists in secondary care. CONCLUSIONS: Characteristics and treatments
      of unselected patients with stable ischemic heart disease in Austria resemble the
      pattern of large international registries of stable ischemic heart disease, with
      the exception that diabetes and systemic hypertension were more prevalent.

PMID- 28448603
TI  - Evaluation of immunogenicity and protective efficacy of recombinant outer
      membrane proteins of Haemophilus parasuis serovar 5 in a murine model.
AB  - Glasser's disease is an economically important infectious disease of pigs caused
      by Haemophilus parasuis. Few vaccines are currently available that could provide
      effective cross-protection against various serovars of H. parasuis. In this
      study, five OMPs (OppA, TolC, HxuC, LppC, and HAPS_0926) identified by
      bioinformatic approaches, were cloned and expressed as recombinant proteins.
      Antigenicity of the purified proteins was verified through Western blotting, and
      primary screening for protective potential was evaluated in vivo. Recombinant
      TolC (rTolC), rLppC, and rHAPS_0926 proteins showing marked protection of mice
      against H. parasuis infection, and were further evaluated individually or in
      combination. Mice treated with these three OMPs produced humoral and host cell
      mediated responses, with a significant rise in antigen-specific IgG titer and
      lymphoproliferative response in contrast with the mock-immunized group.
      Significant increases were noted in CD4+, CD8+ T cells, and three cytokines (IL
      2, IL-4, and IFN-gamma) in vaccinated animals. The antisera against candidate
      antigens could efficiently impede bacterial survival in whole blood bactericidal
      assay against H. parasuis infection. The multi-protein vaccine induced more
      pronounced immune responses and offered better protection than individual
      vaccines. Our findings indicate that these three OMPs are promising antigens for
      the development of multi-component subunit vaccines against Glasser's disease.

PMID- 28448604
TI  - Non invasive imaging assessment of the biodistribution of GSK2849330, an ADCC and
      CDC optimized anti HER3 mAb, and its role in tumor macrophage recruitment in
      human tumor-bearing mice.
AB  - The purpose of this work was to use various molecular imaging techniques to non
      invasively assess GSK2849330 (anti HER3 ADCC and CDC enhanced 'AccretaMab'
      monoclonal antibody) pharmacokinetics and pharmacodynamics in human xenograft
      tumor-bearing mice. Immuno-PET biodistribution imaging of radiolabeled 89Zr
      GSK2849330 was assessed in mice with HER3 negative (MIA-PaCa-2) and positive (CHL
      1) human xenograft tumors. Dose dependency of GSK2849330 disposition was assessed
      using varying doses of unlabeled GSK2849330 co-injected with 89Zr-GSK2849330. In
      vivo NIRF optical imaging and ex-vivo confocal microscopy were used to assess the
      biodistribution of GSK2849330 and the HER3 receptor occupancy in HER3 positive
      xenograft tumors (BxPC3, and CHL-1). Ferumoxytol (USPIO) contrast-enhanced MRI
      was used to investigate the effects of GSK2849330 on tumor macrophage content in
      CHL-1 xenograft bearing mice. Immuno-PET imaging was used to monitor the whole
      body drug biodistribution and CHL-1 xenograft tumor uptake up to 144 hours post
      injection of 89Zr-GSK2849330. Both hepatic and tumor uptake were dose dependent
      and saturable. The optical imaging data in the BxPC3 xenograft tumor confirmed
      the tumor dose response finding in the Immuno-PET study. Confocal microscopy
      showed a distinguished cytoplasmic punctate staining pattern within individual
      CHL-1 cells. GSK2849330 inhibited tumor growth and this was associated with a
      significant decrease in MRI signal to noise ratio after USPIO injection and with
      a significant increase in tumor macrophages as confirmed by a quantitative
      immunohistochemistry analysis. By providing both dose response and time course
      data from both 89Zr and fluorescently labeled GSK2849330, complementary imaging
      studies were used to characterize GSK2849330 biodistribution and tumor uptake in
      vivo. Ferumoxytol-enhanced MRI was used to monitor aspects of the immune system
      response to GSK2849330. Together these approaches potentially provide clinically
      translatable, non-invasive techniques to support dose optimization, and assess
      immune activation and anti-tumor responses.

PMID- 28448606
TI  - A feeding protocol for delivery of agents to assess development in Varroa mites.
AB  - A novel feeding protocol for delivery of bio-active agents to Varroa mites was
      developed by providing mites with honey bee larva hemolymph supplemented with
      cultured insect cells and selected materials delivered on a fibrous cotton
      substrate. Mites were starved, fed on treated hemolymph to deliver selected
      agents and then returned to bee larvae. Transcript levels of two reference genes,
      actin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as well as for nine
      selected genes involved in reproductive processes showed that the starvation and
      feeding protocol periods did not pose a high level of stress to the mites as
      transcript levels remained comparable between phoretic mites and those completing
      the protocol. The feeding protocol was used to deliver molecules such as hormone
      analogs or plasmids. Mites fed with Tebufenozide, an ecdysone analog, had higher
      transcript levels of shade than untreated or solvent treated mites. In order to
      extend this feeding protocol, cultured insect cells were incorporated to a final
      ratio of 1 part cells and 2 parts hemolymph. Although supplementation with Bombyx
      mori Bm5 cells increased the amount of hemolymph consumed per mite, there was a
      significant decrease in the percentage of mites that fed and survived. On the
      other hand, Drosophila melanogaster S2 cells reduced significantly the percentage
      of mites that fed and survived as well as the amount of hemolymph consumed. The
      feeding protocol provides a dynamic platform with which to challenge the Varroa
      mite to establish efficacy of control agents for this devastating honey bee pest.

PMID- 28448607
TI  - Complementing the topsoil information of the Land Use/Land Cover Area Frame
      Survey (LUCAS) with modelled N2O emissions.
AB  - Two objectives of the Common Agricultural Policy post-2013 (CAP, 2014-2020) in
      the European Union (EU) are the sustainable management of natural resources and
      climate smart agriculture. To understand the CAP impact on these priorities, the
      Land Use/Cover statistical Area frame Survey (LUCAS) employs direct field
      observations and soil sub-sampling across the EU. While a huge amount of
      information can be retrieved from LUCAS points for monitoring the environmental
      status of agroecosystems and assessing soil carbon sequestration, a fundamental
      aspect relating to climate change action is missing, namely nitrous oxide (N2O)
      soil emissions. To fill this gap, we ran the DayCent biogeochemistry model for
      more than 11'000 LUCAS sampling points under agricultural use, assessing also the
      model uncertainty. The results showed that current annual N2O emissions followed
      a skewed distribution with a mean and median values of 2.27 and 1.71 kg N ha-1 yr
      1, respectively. Using a Random Forest regression for upscaling the modelled
      results to the EU level, we estimated direct soil emissions of N2O in the range
      of 171-195 Tg yr-1 of CO2eq. Moreover, the direct regional upscaling using
      modelled N2O emissions in LUCAS points was on average 0.95 Mg yr-1 of CO2eq. per
      hectare, which was within the range of the meta-model upscaling (0.92-1.05 Mg ha
      1 yr-1 of CO2eq). We concluded that, if information on management practices would
      be made available and model bias further reduced by N2O flux measurement at
      representative LUCAS points, the combination of the land use/soil survey with a
      well calibrated biogeochemistry model may become a reference tool to support
      agricultural, environmental and climate policies.

PMID- 28448605
TI  - Vasopressor use following traumatic injury - A single center retrospective study.
AB  - OBJECTIVES: Vasopressors are not recommended by current trauma guidelines, but
      recent reports indicate that they are commonly used. We aimed to describe the
      early hemodynamic management of trauma patients outside densely populated urban
      centers. METHODS: We conducted a single-center retrospective cohort study in a
      Canadian regional trauma center. All adult patients treated for traumatic injury
      in 2013 who died within 24 hours of admission or were transferred to the
      intensive care unit were included. A systolic blood pressure <90 mmHg, a mean
      arterial pressure <60 mmHg, the use of vasopressors or >=2 L of intravenous
      fluids defined hemodynamic instability. Main outcome measures were use of
      intravenous fluids and vasopressors prior to surgical or endovascular management.
      RESULTS: Of 111 eligible patients, 63 met our criteria for hemodynamic
      instability. Of these, 60 (95%) had sustained blunt injury and 22 (35%) had
      concomitant severe traumatic brain injury. The subgroup of patients referred from
      a primary or secondary hospital (20 of 63, 32%) had significantly longer
      transport times (243 vs. 61 min, p<0.01). Vasopressors, used in 26 patients
      (41%), were independently associated with severe traumatic brain injury (odds
      ratio 10.2, 95% CI 2.7-38.5). CONCLUSIONS: In this cohort, most trauma patients
      had suffered multiple blunt injuries. Patients were likely to receive
      vasopressors during the early phase of trauma care, particularly if they
      exhibited signs of neurologic injury. While these results may be context
      specific, determining the risk-benefit trade-offs of fluid resuscitation,
      vasopressors and permissive hypotension in specific patients subgroups
      constitutes a priority for trauma research going forwards.

PMID- 28448608
TI  - More intelligent extraverts are more likely to deceive.
AB  - The tendency to lie is a part of personality. But are personality traits the only
      factors that make some people lie more often than others? We propose that
      cognitive abilities have equal importance. People with higher cognitive abilities
      are better, and thus more effective liars. This might reinforce using lies to
      solve problems. Yet, there is no empirical research that shows this relationship
      in healthy adults. Here we present three studies in which the participants had
      free choice about their honesty. We related differences in cognitive abilities
      and personality to the odds of lying. Results show that personality and
      intelligence are both important. People low on agreeableness and intelligent
      extraverts are most likely to lie. This suggests that intelligence might mediate
      the relationship between personality traits and lying frequency. While
      personality traits set general behavioral tendencies, intelligence and
      environment set boundaries.

PMID- 28448609
TI  - Six autoantibodies associated with autoimmune encephalitis are not detectable in
      the cerebrospinal fluid of suicide attempters.
AB  - Previous findings suggest a link between neuroinflammatory processes and
      suicidality. Despite several lines of evidence supporting this link, including
      increased pro-inflammatory markers in blood-, cerebrospinal fluid (CSF)- and in
      post-mortem brain samples from suicidal individuals, the underlying mechanisms
      remain poorly understood. In this pilot study, we explored the possibility that
      autoimmune encephalopathies might be found among suicide attempters. We analysed
      the presence of six different autoantibodies (N-methyl-D-aspartate receptor, the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazol-propionic acid receptor, the gamma
      amino-butyric acid B-receptor, the leucine-rich, glioma-inactivated 1, the
      contactin-associated protein-like 2, and the dipeptidyl-peptidase-like protein
      6), all previously associated with psychopathology, in CSF samples from 29
      unmedicated suicide attempters. Five of these subjects had high CSF/serum albumin
      ratio, indicative of increased blood-brain-barrier permeability. We were not able
      to detect any of these autoantibodies in the CSF samples. These pilot data do not
      support a role for autoimmune encephalopathies in suicidal behaviour, although
      the presence of lower levels of these autoantibodies cannot be ruled out in these
      patients.

PMID- 28448610
TI  - Characterization and expression analysis of Galnts in developing
      Strongylocentrotus purpuratus embryos.
AB  - Mucin-type O-glycosylation is a ubiquitous posttranslational modification in
      which N-Acetylgalactosamine (GalNAc) is added to the hydroxyl group of select
      serine or threonine residues of a protein by the family of UDP-GalNAc:Polypeptide
      N-Acetylgalactosaminyltransferases (GalNAc-Ts; EC 2.4.1.41). Previous studies
      demonstrate that O-glycosylation plays essential roles in protein function, cell
      cell interactions, cell polarity and differentiation in developing mouse and
      Drosophila embryos. Although this type of protein modification is highly
      conserved among higher eukaryotes, little is known about this family of enzymes
      in echinoderms, basal deuterostome relatives of the chordates. To investigate the
      potential role of GalNAc-Ts in echinoderms, we have begun the characterization of
      this enzyme family in the purple sea urchin, S. purpuratus. We have fully or
      partially cloned a total of 13 genes (SpGalnts) encoding putative sea urchin
      SpGalNAc-Ts, and have confirmed enzymatic activity of five recombinant proteins.
      Amino acid alignments revealed high sequence similarity among sea urchin and
      mammalian glycosyltransferases, suggesting the presence of putative orthologues.
      Structural models underscored these similarities and helped reconcile some of the
      substrate preferences observed. Temporal and spatial expression of SpGalnt
      transcripts, was studied by whole-mount in situ hybridization. We found that many
      of these genes are transcribed early in developing embryos, often with restricted
      expression to the endomesodermal region. Multicolor fluorescent in situ
      hybridization (FISH) demonstrated that transcripts encoding SpGalnt7-2 co
      localized with both Endo16 (a gene expressed in the endoderm), and Gcm (a gene
      expressed in secondary mesenchyme cells) at the early blastula stage, 20 hours
      post fertilization (hpf). At late blastula stage (28 hpf), SpGalnt7-2 message co
      expresses with Gcm, suggesting that it may play a role in secondary mesenchyme
      development. We also discovered that morpholino-mediated knockdown of SpGalnt13
      transcripts, results in a deficiency of embryonic skeleton and neurons,
      suggesting that mucin-type O-glycans play essential roles during embryonic
      development in S. purpuratus.

PMID- 28448611
TI  - Insights into intercontinental spread of Zika virus.
AB  - The epidemic of Zika virus (ZIKV) infection in South America has led to World
      Health Organization's declaration of a Public Health Emergency of International
      Concern. To further inform effective public health policy, an understanding of
      ZIKV's transmission mechanisms is crucial. To characterize the intercontinental
      transmission of ZIKV, we compiled and analyzed more than 250 gene sequences
      together with their sequence-related geographic and temporal information, sampled
      across 27 countries spanning from 1947 to 2016. After filtering and selecting
      appropriate sequences, extensive phylogenetic analyses were performed. Although
      phylogeographic reconstruction supported the transmission route of the virus in
      Africa, South-eastern Asia, Oceania and Latin America, we discovered that the
      Eastern Africa origin of ZIKV was disputable. On a molecular level, purifying
      selection was found to be largely responsible for the evolution of non-structural
      protein 5 and envelope protein E. Our dataset and ancestral sequences
      reconstruction analysis captured previously unidentified amino acid changes
      during evolution. Finally, based on the estimation of the time to the most recent
      common ancestors for the non-structural protein 5 gene, we hypothesized potential
      specific historic events that occurred in the 1940s and might have facilitated
      the spread of Zika virus from Africa to South-eastern Asia. Our findings provide
      new insights into the transmission characteristics of ZIKV, while further genetic
      and serologic studies are warranted to support the design of tailored prevention
      strategies.

PMID- 28448612
TI  - Hydrodynamic characteristics of submerged vegetation flow with non-constant
      vertical porosity.
AB  - In order to investigate the influence of the vertical variation of porosity on
      open-channel flow with submerged vegetation, vertical non-homogeneous stumps and
      stems in submerged vegetation flow are simulated with truncated cones in a
      laboratory flume. First, porosity is defined as a function of water depth. A new
      governing equation for vegetation flow is established on the basis of the
      poroelastic media flow theory, and its analytical solution is obtained with the
      finite analytic method. Then, the fitting expression of permeability is
      established with experimental data, which shows the variation in permeability
      with vertical porosity and vegetation density. Finally, the calculated velocity
      distribution is compared with the measured velocity distribution. The theoretical
      results are in good agreement with the experimental data, which indicates that
      the theoretical formula accurately and practically predicts vertical velocity
      distribution in complex open-channel flow with submerged vegetation.

PMID- 28448613
TI  - Water temperature-dependent degradation of environmental DNA and its relation to
      bacterial abundance.
AB  - Environmental DNA (eDNA) is DNA shed by organisms into surrounding environments
      such as soil and water. The new methods using eDNA as a marker for species
      detection are being rapidly developed. Here we explore basic knowledge regarding
      the dependence of the eDNA degradation rate on time and water temperature, and
      the relationship between eDNA degradation and bacterial abundance. This subject
      has not been well clarified, even though it is essential for improving the
      reliability of eDNA analysis. To determine the time- and water temperature
      dependent degradation of eDNA, river water was sampled and eDNA concentrations
      were determined for ayu sweetfish (Plecoglossus altivelis altivelis) and common
      carp (Cyprinus carpio) at seven time points, over a 48-h period, and at three
      different water temperatures. The degradation of eDNA was modeled for each
      species using an existing exponential decay model with an extension to include
      water temperature effects. The degradation models were constructed for ayu
      sweetfish as Nt = 229,901.2 * exp [- (0.01062 * k - 0.07081) * t] and for common
      carp as Nt = 2,558.0 * exp [- (0.01075 * k - 0.07372) * t]. Nt is the DNA
      concentration at time t (elapsed time in hours) and k is the water temperature (
      degrees C). We also measured the concentration of eDNA derived from purified
      genomic DNA of the common carp, which was spiked into aquarium water without the
      target species, and we measured the bacterial abundance in the sample water after
      12 and 24 h of incubation. Environmental DNA degradation was accelerated at
      higher water temperatures (generalized linear model, GLM; p < 0.001), but
      bacterial abundance did not have a significant effect on eDNA degradation (GLM, p
      = 0.097). These results suggest that the proper treatment of this temperature
      effect in data interpretations and adjustments would increase the reliability of
      eDNA analysis in future studies.

PMID- 28448614
TI  - Obtaining retrotransposon sequences, analysis of their genomic distribution and
      use of retrotransposon-derived genetic markers in lentil (Lens culinaris Medik.).
AB  - Retrotransposons with long terminal repeats (LTR-RTs) are widespread mobile
      elements in eukaryotic genomes. We obtained a total of 81 partial LTR-RT
      sequences from lentil corresponding to internal retrotransposon components and
      LTRs. Sequences were obtained by PCR from genomic DNA. Approximately 37% of the
      LTR-RT internal sequences presented premature stop codons, pointing out that
      these elements must be non-autonomous. LTR sequences were obtained using the iPBS
      technique which amplifies sequences between LTR-RTs. A total of 193
      retrotransposon-derived genetic markers, mainly iPBS, were used to obtain a
      genetic linkage map from 94 F7 inbred recombinant lines derived from the cross
      between the cultivar Lupa and the wild ancestor L. culinaris subsp. orientalis.
      The genetic map included 136 markers located in eight linkage groups. Clusters of
      tightly linked retrotransposon-derived markers were detected in linkage groups
      LG1, LG2, and LG6, hence denoting a non-random genomic distribution. Phylogenetic
      analyses identified the LTR-RT families in which internal and LTR sequences are
      included. Ty3-gypsy elements were more frequent than Ty1-copia, mainly due to the
      high Ogre element frequency in lentil, as also occurs in other species of the
      tribe Vicieae. LTR and internal sequences were used to analyze in silico their
      distribution among the contigs of the lentil draft genome. Up to 8.8% of the
      lentil contigs evidenced the presence of at least one LTR-RT similar sequence. A
      statistical analysis suggested a non-random distribution of these elements within
      of the lentil genome. In most cases (between 97% and 72%, depending on the LTR-RT
      type) none of the internal sequences flanked by the LTR sequence pair was
      detected, suggesting that defective and non-autonomous LTR-RTs are very frequent
      in lentil. Results support that LTR-RTs are abundant and widespread throughout of
      the lentil genome and that they are a suitable source of genetic markers useful
      to carry out further genetic analyses.

PMID- 28448615
TI  - Emphysema is associated with thoracic vertebral bone attenuation on chest CT scan
      in HIV-infected individuals.
AB  - BACKGROUND: Age-related chronic diseases are prevalent in HIV-infected persons in
      the antiretroviral therapy (ART) era. Bone mineral density (BMD) loss and
      emphysema have separately been shown to occur at a younger age and with lesser
      risk exposure in HIV-infected compared to HIV-uninfected individuals. In non-HIV
      infected smokers, emphysema has been shown to independently predict low BMD. We
      hypothesized that emphysema would independently associate with thoracic vertebral
      bone attenuation, a surrogate for bone mineral density, in HIV-infected
      individuals. METHODS: Clinical, pulmonary function, and radiographic data were
      analyzed for 164 individuals from the University of Pittsburgh's HIV Lung
      Research Center cohort. Chest CT scans were used to quantify emphysema and
      compute Hounsfield Unit (HU) attenuation of the 4th, 7th, and 10th thoracic
      vertebrae. The association between mean HU attenuation values across the three
      vertebrae and radiographic emphysema, age, sex, body mass index (BMI), steroid
      use, viral load, CD4 count, and forced expiratory volume in the first second
      (FEV1) was assessed by univariate and multivariate analyses. RESULTS: In
      univariate analysis, mean HU attenuation decreased with increasing age (p<0.001),
      pack years (p = 0.047), and percent emphysema (p<0.001). In a multivariable
      model, including pack years, age, sex, ART and steroid use, greater emphysema was
      independently associated with this surrogate marker of BMD in HIV-infected
      individuals (p = 0.034). CONCLUSIONS: The association of emphysema with thoracic
      bone attenuation in HIV-infected individuals is consistent with previous reports
      in non-HIV infected smokers. These findings suggest that emphysema should be
      considered a potential marker of osteoporosis risk in HIV-infected individuals.

PMID- 28448616
TI  - Abundance profiling of specific gene groups using precomputed gut metagenomes
      yields novel biological hypotheses.
AB  - The gut microbiota is essentially a multifunctional bioreactor within a human
      being. The exploration of its enormous metabolic potential provides insights into
      the mechanisms underlying microbial ecology and interactions with the host. The
      data obtained using "shotgun" metagenomics capture information about the whole
      spectrum of microbial functions. However, each new study presenting new
      sequencing data tends to extract only a little of the information concerning the
      metabolic potential and often omits specific functions. A meta-analysis of the
      available data with an emphasis on biomedically relevant gene groups can unveil
      new global trends in the gut microbiota. As a step toward the reuse of
      metagenomic data, we developed a method for the quantitative profiling of user
      defined groups of genes in human gut metagenomes. This method is based on the
      quick analysis of a gene coverage matrix obtained by pre-mapping the metagenomic
      reads to a global gut microbial catalogue. The method was applied to profile the
      abundance of several gene groups related to antibiotic resistance, phages,
      biosynthesis clusters and carbohydrate degradation in 784 metagenomes from
      healthy populations worldwide and patients with inflammatory bowel diseases and
      obesity. We discovered country-wise functional specifics in gut resistome and
      virome compositions. The most distinct features of the disease microbiota were
      found for Crohn's disease, followed by ulcerative colitis and obesity. Profiling
      of the genes belonging to crAssphage showed that its abundance varied across the
      world populations and was not associated with clinical status. We demonstrated
      temporal resilience of crAssphage and the influence of the sample preparation
      protocol on its detected abundance. Our approach offers a convenient method to
      add value to accumulated "shotgun" metagenomic data by helping researchers state
      and assess novel biological hypotheses.

PMID- 28448617
TI  - Seagrass blue carbon spatial patterns at the meadow-scale.
AB  - Most information on seagrass carbon burial derives from point measurements, which
      are sometimes scaled by meadow area to estimate carbon stocks; however, sediment
      organic carbon (Corg) concentrations may vary with distance from the meadow edge,
      resulting in spatial gradients that affect the accuracy of stock estimates. We
      mapped sediment Corg concentrations throughout a large (6 km2) restored seagrass
      meadow to determine whether Corg distribution patterns exist at different spatial
      scales. The meadow originated from <=1-acre plots seeded between 2001 and 2004,
      so we expected Corg to vary spatially according to the known meadow age at sample
      sites and with proximity to the meadow edge. Applying spatial autoregressive
      models allowed us to control for spatial autocorrelation and quantify the
      relative effects of edge proximity and age on Corg concentrations. We found that
      edge proximity, not age, significantly predicted the meadow-scale Corg
      distribution. We also evaluated relationships between Corg and a variety of
      specific explanatory variables, including site relative exposure, shoot density,
      sediment grain size, and bathymetry. Factors known to affect carbon burial at the
      plot-scale, such as meadow age and shoot density, were not significant controls
      on the meadow-scale Corg distribution. Strong correlations between Corg, grain
      size, and edge proximity suggest that current attenuation increases fine-sediment
      deposition and, therefore, carbon burial with distance into the meadow. By
      mapping the sediment Corg pool, we provide the first accurate quantification of
      an enhanced carbon stock attributable to seagrass restoration. The top 12 cm of
      the bed contain 3660 t Corg, approximately 1200 t more Corg than an equal area of
      bare sediment. Most of that net increase is concentrated in a meadow area with
      low tidal current velocities. Managers should account for the effects of meadow
      configuration and current velocity when estimating seagrass blue carbon stocks.
      Our results suggest that a large, contiguous meadow should store more blue carbon
      than an equal area of small meadow patches.

PMID- 28448618
TI  - rs10499194 polymorphism in the tumor necrosis factor-alpha inducible protein 3
      (TNFAIP3) gene is associated with type-1 autoimmune hepatitis risk in Chinese Han
      population.
AB  - Previous studies have found that the polymorphisms of tumor necrosis factor-alpha
      induced protein 3 (TNFAIP3) were associated with several autoimmune diseases.
      However, the role of TNFAIP3 polymorphisms in type-1 autoimmune hepatitis (AIH-1)
      remained unclear. The present study aimed to clarify the association of TNFAIP3
      polymorphisms with AIH-1 risk in a Chinese Han population. The TaqMan SNP
      genotyping assay was used to determine the distribution of TNFAIP3 polymorphisms
      in 432 AIH-1 patients and 500 healthy controls. The association of TNFAIP3
      polymorphisms and clinical characteristic was further evaluated. Five TNFAIP3
      polymorphisms (rs2230926, rs5029939, rs10499194, rs6920220, rs582757) were
      analyzed in the present study. No significant association could be observed
      between rs2230926, rs5029939, rs6920220, rs582757 and the susceptibility to AIH-1
      in Chinese Han population. Compared with wild-type genotype CC at rs10499194,
      individuals carrying CT genotype had a significantly increased risk for
      developing AIH-1 (OR = 2.32, 95%CI 1.44-3.74). Under a dominant model, CT/TT
      carriers have a 140% increased risk of AIH-1 than CC carriers (OR = 2.40, 95%CI
      1.50-3.87). The rs10499194 T allele was also found to be significantly associated
      with AIH-1 risk (OR = 2.41, 95%CI 1.51-3.82). In addition, higher serum ALT, AST
      levels and more common cirrhosis were observed in AIH-1 patients with T allele
      (CT/TT) than those with CC genotype. In conclusion, TNFAIP3 rs10499194 T allele
      and CT genotype were associated with an increased risk for AIH-1, suggesting
      rs10499194 polymorphism as a candidate of susceptibility locus to AIH-1.

PMID- 28448620
TI  - Correction: Systematics of the Dendropsophus leucophyllatus species complex
      (Anura: Hylidae): Cryptic diversity and the description of two new species.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0171785.].

PMID- 28448619
TI  - Pyridoxal phosphate synthases PdxS/PdxT are required for Actinobacillus
      pleuropneumoniae viability, stress tolerance and virulence.
AB  - Pyridoxal 5'-phosphate (PLP) is an essential cofactor for numerous enzymes
      involved in a diversity of cellular processes in living organisms. Previous
      analysis of the Actinobacillus pleuropneumoniae S-8 genome sequence revealed the
      presence of pdxS and pdxT genes, which are implicated in deoxyxylulose 5
      phosphate (DXP)-independent pathway of PLP biosynthesis; however, little is known
      about their roles in A. pleuropneumoniae pathogenicity. Our data demonstrated
      that A. pleuropneumoniae could synthesize PLP by PdxS and PdxT enzymes.
      Disruption of the pdxS and pdxT genes rendered the pathogen auxotrophic for PLP,
      and the defective growth as a result of these mutants was chemically compensated
      by the addition of PLP, suggesting the importance of PLP production for A.
      pleuropneumoniae growth and viability. Additionally, the pdxS and pdxT deletion
      mutants displayed morphological defects as indicated by irregular and aberrant
      shapes in the absence of PLP. The reduced growth of the pdxS and pdxT deletion
      mutants under osmotic and oxidative stress conditions suggests that the PLP
      synthases PdxS/PdxT are associated with the stress tolerance of A.
      pleuropneumoniae. Furthermore, disruption of the PLP biosynthesis pathway led to
      reduced colonization and attenuated virulence of A. pleuropneumoniae in the
      BALB/c mouse model. The data presented in this study reveal the critical role of
      PLP synthases PdxS/PdxT in viability, stress tolerance, and virulence of A.
      pleuropneumoniae.

PMID- 28448621
TI  - Biochar from "Kon Tiki" flame curtain and other kilns: Effects of nutrient
      enrichment and kiln type on crop yield and soil chemistry.
AB  - Biochar application to soils has been investigated as a means of improving soil
      fertility and mitigating climate change through soil carbon sequestration. In the
      present work, the invasive shrub "Eupatorium adenophorum" was utilized as a
      sustainable feedstock for making biochar under different pyrolysis conditions in
      Nepal. Biochar was produced using several different types of kilns; four sub
      types of flame curtain kilns (deep-cone metal kiln, steel shielded soil pit,
      conical soil pit and steel small cone), brick-made traditional kiln, traditional
      earth-mound kiln and top lift up draft (TLUD). The resultant biochars showed
      consistent pH (9.1 +/- 0.3), cation exchange capacities (133 +/- 37 cmolc kg-1),
      organic carbon contents (73.9 +/- 6.4%) and surface areas (35 to 215 m2/g) for
      all kiln types. A pot trial with maize was carried out to investigate the effect
      on maize biomass production of the biochars made with various kilns, applied at
      1% and 4% dosages. Biochars were either pretreated with hot or cold mineral
      nutrient enrichment (mixing with a nutrient solution before or after cooling
      down, respectively), or added separately from the same nutrient dosages to the
      soil. Significantly higher CEC (P< 0.05), lower Al/Ca ratios (P< 0.05), and high
      OC% (P<0.001) were observed for both dosages of biochar as compared to non
      amended control soils. Importantly, the study showed that biochar made by flame
      curtain kilns resulted in the same agronomic effect as biochar made by the other
      kilns (P > 0.05). At a dosage of 1% biochar, the hot nutrient-enriched biochar
      led to significant increases of 153% in above ground biomass production compared
      to cold nutrient-enriched biochar and 209% compared to biochar added separately
      from the nutrients. Liquid nutrient enhancement of biochar thus improved
      fertilizer effectiveness compared to separate application of biochar and
      fertilizer.

PMID- 28448622
TI  - Goniodysgenesis variability and activity of CYP1B1 genotypes in primary
      congenital glaucoma.
AB  - Mutations in the CYP1B1 gene are currently the main known genetic cause of
      primary congenital glaucoma (PCG), a leading cause of blindness in children.
      Here, we analyze for the first time the CYP1B1 genotype activity and the
      microscopic and clinical phenotypes in human PCG. Surgical pieces from
      trabeculectomy from patients with PCG (n = 5) and sclerocorneal rims (n = 3) from
      cadaver donors were processed for transmission electron microscopy. Patients were
      classified into three groups depending on goniodysgenesis severity, which was
      influenced by CYP1B1 enzymatic activity. The main histological changes observed
      in the outflow pathway of patients with PCG and mutations in CYP1B1 were: i)
      underdeveloped collector channels and the Schlemm's canal; ii) abnormal insertion
      of the ciliary muscle; iii) death of the trabecular endothelial cells. Our
      findings could be useful in improving treatment strategy of PCG associated with
      CYP1B1 mutations.

PMID- 28448623
TI  - Development of the cutaneous microbiome in the preterm infant: A prospective
      longitudinal study.
AB  - BACKGROUND: Neonatal sepsis in preterm infants is often due to organisms that
      colonize the skin including Staphylococcus spp. and Candida spp. Development and
      maturation of the skin microbiome in the neonatal period, especially in preterm
      infants, may be critical in preventing colonization with pathogens and subsequent
      progression to neonatal sepsis. Development of the skin microbiome in preterm
      infants or its determinants in the first 4 weeks of life has not been evaluated.
      METHODS: We evaluated the skin microbiome from three body sites, antecubital
      fossa, forehead and gluteal region, in a prospective cohort of 15 preterm (birth
      weight < 1500 g and < 32 weeks of gestation) and 15 term neonates. The microbiome
      community membership and relative abundance were evaluated by amplification and
      sequencing the bacterial V3-V5 region of the16S rRNA gene on the 454 GS FLX
      platform. We used linear mixed effects models to analyze longitudinal data.
      RESULTS: The structure and composition of the skin microbiome did not differ
      between the three sampling sites for term and preterm infants in the neonatal
      period. However, skin bacterial richness was positively associated with
      gestational age in the first four weeks of life. Intravenous antibiotics
      negatively impacted the bacterial diversity of the skin but we did not see
      differences with respect to feeding or mode of delivery. CONCLUSIONS: Gestational
      age, which influences the maturity of skin structure and function, is associated
      with the development of the preterm cutaneous microbiome. Understanding the
      maturation of a healthy skin microbiome, prevention of pathogen colonization and
      its role in the development of immunity will be pivotal in the development of
      novel interventions to prevent infections in critically ill preterm infants.

PMID- 28448624
TI  - Overexpression of the protein phosphatase 2A regulatory subunit a gene ZmPP2AA1
      improves low phosphate tolerance by remodeling the root system architecture of
      maize.
AB  - Phosphate (Pi) limitation is a constraint for plant growth and development in
      many natural and agricultural ecosystems. In this study, a gene encoding Zea mays
      L. protein phosphatase 2A regulatory subunit A, designated ZmPP2AA1, was induced
      in roots by low Pi availability. The function of the ZmPP2AA1 gene in maize was
      analyzed using overexpression and RNA interference. ZmPP2AA1 modulated root
      gravitropism, negatively regulated primary root (PR) growth, and stimulated the
      development of lateral roots (LRs). A detailed characterization of the root
      system architecture (RSA) in response to different Pi concentrations with or
      without indole-3-acetic acid and 1-N-naphthylphthalamic acid revealed that auxin
      was involved in the RSA response to low Pi availability. Overexpression of
      ZmPP2AA1 enhanced tolerance to Pi starvation in transgenic maize in hydroponic
      and soil pot experiments. An increased dry weight (DW), root-to-shoot ratio, and
      total P content and concentration, along with a delayed and reduced accumulation
      of anthocyanin in overexpressing transgenic maize plants coincided with their
      highly branched root system and increased Pi uptake capability under low Pi
      conditions. Inflorescence development of the ZmPP2AA1 overexpressing line was
      less affected by low Pi stress, resulting in higher grain yield per plant under
      Pi deprivation. These data reveal the biological function of ZmPP2AA1, provide
      insights into a linkage between auxin and low Pi responses, and drive new
      strategies for the efficient utilization of Pi by maize.

PMID- 28448625
TI  - Structural and functional studies of ferredoxin and oxygenase components of 3
      nitrotoluene dioxygenase from Diaphorobacter sp. strain DS2.
AB  - 3-nitrotoluene dioxygenase (3NTDO) from Diaphorobacter sp. strain DS2 catalyses
      the conversion of 3-nitrotoluene (3NT) into a mixture of 3- and 4-methylcatechols
      with release of nitrite. We report here, X-ray crystal structures of oxygenase
      and ferredoxin components of 3NTDO at 2.9 A and 2.4 A, respectively. The residues
      responsible for nitrite release in 3NTDO were further probed by four single and
      two double mutations in the catalytic site of alpha-subunit of the dioxygenase.
      Modification of Val 350 to Phe, Ile 204 to Ala, and Asn258 to Val by site
      directed mutagenesis resulted in inactive enzymes revealing the importance of
      these residues in catalysis. Docking studies of meta nitrotoluene to the active
      site of 3NTDO suggested possible orientations of binding that favor the formation
      of 3-methylcatechol (3MC) over 4-methylcatechol energetically. The electron
      transfer pathway from ferredoxin subunit to the active site of the oxygenase
      subunit is also proposed.

PMID- 28448626
TI  - Genetic background-dependent effects of murine micro RNAs on circadian clock
      function.
AB  - MicroRNAs (miRs) are important regulators of a wide range of biological
      processes. Antagomir studies suggest an implication of miR-132 in the
      functionality of the mammalian circadian clock. miR-212 and miR-132 are tandemly
      processed from the same transcript and share the same seed region. We found the
      clock modulator miR-132 and miR-212 to be expressed rhythmically in the central
      circadian clock. Consequently, mRNAs implicated in circadian functions may likely
      be targeted by both miRs. To further characterize the circadian role we generated
      mice with stable deletion of the miR-132/212 locus and compared the circadian
      behavior of mutant and wild-type control animals on two genetic backgrounds
      frequently used in chronobiological research, C57BL/6N and 129/Sv. Surprisingly,
      the wheel-running activity phenotype of miR mutant mice was highly background
      specific. A prolonged circadian free-running period in constant darkness was
      found in 129/Sv, but not in C57BL/6N miR-132/212 knockout mice. In contrast, in
      C57BL/6N, but not in 129/Sv miRNA-132/212 knockout mice a lengthened free-running
      period was observed in constant light conditions. Furthermore, miR-132/212
      knockout mice on 129/Sv background exhibited enhanced photic phase shifts of
      locomotor activity accompanied by reduced light induction of Period gene
      transcription in the SCN. This phenotype was absent in miRNA-132/212 knockout
      mice on a C57BL/6N background. Together, our results reveal a strain and light
      regimen-specific function of miR-132/212 in the circadian clock machinery
      suggesting that miR-132 and miR-212 act as background-dependent circadian rhythm
      modulators.

PMID- 28448627
TI  - Engineering chimeric human and mouse major histocompatibility complex (MHC) class
      I tetramers for the production of T-cell receptor (TCR) mimic antibodies.
AB  - Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are
      among the most effective classes of novel immunotherapies. However, the majority
      of human proteins and established cancer biomarkers are intracellular. Peptides
      derived from these intracellular proteins are presented on the cell surface by
      major histocompatibility complex class I (MHC-I) and can be targeted by a novel
      class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes
      to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate
      TCRm antibodies and many antibodies recognise the alpha3 domain of MHC-I and
      beta2 microglobulin (beta2m) that are not directly involved in presenting the
      target peptide. Here we describe the production of functional chimeric human
      murine HLA-A2-H2Dd tetramers and modifications that increase their bacterial
      expression and refolding efficiency. These chimeric tetramers were successfully
      used to generate TCRm antibodies against two epitopes derived from wild type
      tumour suppressor p53 (RMPEAAPPV and GLAPPQHLIRV) that have been used in
      vaccination studies. Immunisation with chimeric tetramers yielded no antibodies
      recognising the human alpha3 domain and beta2m and generated TCRm antibodies
      capable of specifically recognising the target peptide/MHC-I complex in fully
      human tetramers and on the cell surface of peptide pulsed T2 cells. Chimeric
      tetramers represent novel immunogens for TCRm antibody production and may also
      improve the yield of tetramers for groups using these reagents to monitor CD8 T
      cell immune responses in HLA-A2 transgenic mouse models of immunotherapy.

PMID- 28448628
TI  - Determinants of formal care use and expenses among in-home elderly in Jing'an
      district, Shanghai, China.
AB  - The need for formal care among the elderly population has been increasing due to
      their greater longevity and the evolution of family structure. We examined the
      determinants of the use and expenses of formal care among in-home elderly adults
      in Shanghai. A two-part model based on the data from the Shanghai Long-Term Care
      Needs Assessment Questionnaire was applied. A total of 8428 participants
      responded in 2014 and 7100 were followed up in 2015. The determinants of the
      probability of using formal care were analyzed in the first part of the model and
      the determinants of formal care expenses were analyzed in the second part.
      Demographic indicators, living arrangements, physical health status, and care
      type in 2014 were selected as independent variables. We found that individuals of
      older age; women; those with higher Activities of Daily Living (ADL) scores;
      those without spouse; those with higher income; those suffering from stroke,
      dementia, lower limb fracture, or advanced tumor; and those with previous
      experience of formal and informal care were more likely to receive formal care in
      2015. Furthermore, age, income and formal care fee in 2014 were significant
      predictors of formal care expenses in 2015. Taken together, the results showed
      that formal care provision in Shanghai was not determined by ADL scores, but was
      instead more related to income. This implied an inappropriate distribution of
      formal care among elderly population in Shanghai. Additionally, it appeared
      difficult for the elderly to quit the formal care once they begun to use it.
      These results highlighted the importance of assessing the need for formal care,
      and suggested that the government offer guidance on formal care use for the
      elderly.

PMID- 28448630
TI  - Correction: Influenza A H5N1 and H7N9 in China: A spatial risk analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0174980.].

PMID- 28448629
TI  - Structure and function of a novel GH8 endoglucanase from the bacterial cellulose
      synthase complex of Raoultella ornithinolytica.
AB  - Cellulose synthesis in bacteria is a complex process involving the concerted
      action of several enzymes whose genes are often organized in operons. This
      process influences many fundamental physiological aspects such as bacteria and
      host interaction, biofilm formation, among others. Although it might sound
      contradictory, the participation of cellulose-degrading enzymes is critical to
      this process. The presence of endoglucanases from family 8 of glycosyl hydrolases
      (GH8) in bacterial cellulose synthase (Bcs) complex has been described in
      different bacteria, including the model organism Komagataeibacter xylinus;
      however, their role in this process is not completely understood. In this study,
      we describe the biochemical characterization and three-dimensional structure of a
      novel GH8 member from Raoultella ornithinolytica, named AfmE1, which was
      previously identified by our group from the metagenomic analysis of the giant
      snail Achatina fulica. Our results demonstrated that AfmE1 is an endo-beta-1,4
      glucanase, with maximum activity in acidic to neutral pH over a wide temperature
      range. This enzyme cleaves cello-oligosaccharides with a degree of polymerization
      >= 5 and presents six glucosyl-binding subsites. The structural comparison of
      AfmE1 with other GH8 endoglucanases showed significant structural dissimilarities
      in the catalytic cleft, particularly in the subsite +3, which correlate with
      different functional mechanisms, such as the recognition of substrate molecules
      having different arrangements and crystallinities. Together, these findings
      provide new insights into molecular and structural features of evolutionarily
      conserved endoglucanases from the bacterial cellulose biosynthetic machinery.

PMID- 28448631
TI  - Biofortification (Se): Does it increase the content of phenolic compounds in
      virgin olive oil (VOO)?
AB  - Extra-Virgin Olive Oil (EVOO) is a fundamental component of the Mediterranean
      diet and it may contain several anti-oxidant substances, such as phenols.
      Previous research has shown that this food may be enriched in phenols by spraying
      a sodium-selenate solution (100 mg L-1 Se) onto the crop canopy before flowering.
      The aim of this research was to evaluate the effect of this Se-fertilization
      before flowering (cv. Leccino) on the phenolic profile of EVOOs, and test to what
      extent such effects depend on the weather pattern, as observed in two contrasting
      experimental seasons (2013 and 2014). Results showed that Se-fertilisation
      enriched EVOOs both in selenium (up to 120 MUg kg-1) and in phenols (up to 401 mg
      kg-1). This latter enrichment was related to an increase in PAL (L-Phenylalanine
      Ammonia-Lyase) activities and it was largely independent on the climatic pattern.
      Considering the phenolic profile, oleacein, ligustroside, aglycone and
      oleocanthal were the most affected compounds and were increased by 57, 50 and
      32%, respectively. All these compounds, especially oleacein, have been shown to
      exert a relevant anti-oxidant activity, contributing both to the shelf-life of
      EVOOs and to positive effects on human health. It is suggested that Se
      fertilisation of olive trees before flowering may be an interesting practice,
      particularly with poor cultivars and cold and rainy weather patterns, which would
      normally lead to the production of EVOOs with unfavourable phenolic profile.

PMID- 28448632
TI  - Correction: Right atrial volume by cardiovascular magnetic resonance predicts
      mortality in patients with heart failure with reduced ejection fraction.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0173245.].

PMID- 28448634
TI  - The not-so-infinite malleability of RNA viruses: Viral and cellular determinants
      of RNA virus mutation rates.

PMID- 28448633
TI  - A commensal streptococcus hijacks a Pseudomonas aeruginosa exopolysaccharide to
      promote biofilm formation.
AB  - Pseudomonas aeruginosa causes devastating chronic pulmonary infections in cystic
      fibrosis (CF) patients. Although the CF airway is inhabited by diverse species of
      microorganisms interlaced within a biofilm, many studies focus on the sole
      contribution of P. aeruginosa pathogenesis in CF morbidity. More recently, oral
      commensal streptococci have been identified as cohabitants of the CF lung, but
      few studies have explored the role these bacteria play within the CF biofilm. We
      examined the interaction between P. aeruginosa and oral commensal streptococci
      within a dual species biofilm. Here we report that the CF P. aeruginosa isolate,
      FRD1, enhances biofilm formation and colonization of Drosophila melanogaster by
      the oral commensal Streptococcus parasanguinis. Moreover, production of the P.
      aeruginosa exopolysaccharide, alginate, is required for the promotion of S.
      parasanguinis biofilm formation and colonization. However, P. aeruginosa is not
      promoted in the dual species biofilm. Furthermore, we show that the streptococcal
      adhesin, BapA1, mediates alginate-dependent enhancement of the S. parasanguinis
      biofilm in vitro, and BapA1 along with another adhesin, Fap1, are required for
      the in vivo colonization of S. parasanguinis in the presence of FRD1. Taken
      together, our study highlights a new association between streptococcal adhesins
      and P. aeruginosa alginate, and reveals a mechanism by which S. parasanguinis
      potentially colonizes the CF lung and interferes with the pathogenesis of P.
      aeruginosa.

PMID- 28448635
TI  - Excited state dynamics of bis-dehydroxycurcumin tert-butyl ester, a diketo
      shifted derivative of the photosensitizer curcumin.
AB  - Bis-dehydroxycurcumin tert-butyl ester (K2T23) is a derivative of the natural
      spice curcumin. Curcumin is widely studied for its multiple therapeutic
      properties, including photosensitized cytotoxicity. However, the full
      exploitation of curcumin phototoxic potential is hindered by the extreme
      instability of its excited state, caused by very efficient non radiative decay by
      means of transfer of the enolic proton to the nearby keto oxygen. K2T23 is
      designed to exhibit a tautomeric equilibrium shifted toward the diketo conformers
      with respect to natural curcumin. This property should endow K2T23 with superior
      excited-state stability when excited in the UVB band, i.e., in correspondence of
      the diketo conformers absorption peaks, making this compound an interesting
      candidate for topical photodynamic therapy of, e.g., skin tumors or oral
      infections. In this work, the tautomeric equilibrium of K2T23 between the keto
      enolic and diketo conformers is assessed in the ground state in several organic
      solvents by UV-visible absorption and by nuclear magnetic resonance. The same
      tautomeric equilibrium is also probed in the excited-state in the same
      environments by means of steady-state fluorescence and time-correlated single
      photon counting measurements. These techniques are also exploited to elucidate
      the excited state dynamics and excited-state deactivation pathways of K2T23,
      which are compared to those determined for several other curcuminoids
      characterized in previous works of ours. The ability of K2T23 in photosensitizing
      the production of singlet oxygen is compared with that of curcumin.

PMID- 28448636
TI  - Successful vitrification of pronuclear-stage pig embryos with a novel
      cryoprotective agent, carboxylated epsilon-poly-L-lysine.
AB  - Vitrification is a powerful tool for the efficient production of offspring
      derived from cryopreserved oocytes or embryos in mammalian species including
      domestic animals. Genome editing technologies such as transcription activator
      like effector nucleases (TALENs) and clustered regularly interspaced short
      palindromic repeats (CRISPR)/ CRISPR-associated (Cas)9 are now available even for
      domestic species, suggesting that the vitrification of embryos at the pronuclear
      stage (PN) will be more important because they could provide genomic host cells
      to be targeted by TALENs or CRISPR/Cas9. Although we reported the successful
      production of piglets derived from vitrified PN embryos by a solid-surface
      vitrification method with glutathione supplementation, further improvements are
      required. The cryoprotective agent (CPA) carboxylated epsilon-poly-L-lysine (COOH
      PLL) was introduced in 2009. COOH-PLL reduces the physical and physiological
      damage caused by cryopreservation in mammalian stem cells and the vitrification
      of mouse oocytes and embryos. Those results suggested that vitrification of COOH
      PLL may help improve the developmental ability of pig embryos vitrified at the PN
      stage. However, it remains unclear whether COOH-PLL is available as a CPA for the
      vitrification of embryos in domestic species. In this study, we evaluated COOH
      PLL as a CPA with ethylene glycol (EG) and Cryotop as a device for the
      vitrification of PN pig embryos. Exposure to vitrification solution supplemented
      with COOH-PLL up to 30% did not decrease developmental ability to the 2-cell
      stage and the blastocyst stage. After warming, most of the vitrified embryos
      survived regardless of the concentration of COOH-PLL (76.0 +/- 11.8% to 91.8 +/-
      4.6%). However, the vitrified embryos without COOH-PLL showed a lower development
      rate up to the blastocyst stage (1.3 +/- 1.0%) compared to the fresh embryos
      (28.4 +/- 5.0%) (p<0.05). In contrast, supplementation of 20% (w/v) COOH-PLL in
      the vitrification solution dramatically improved the developmental ability to
      blastocysts of the vitrified embryos (19.4 +/- 4.6%) compared to those without
      COOH-PLL (p<0.05). After the transfer of embryos vitrified with 30% (v/v) EG and
      20% (w/v) COOH-PLL, we successfully obtained 15 piglets from 8 recipients. Taken
      together, our present findings demonstrate for the first time that COOH-PLL is an
      effective CPA for embryo vitrification in the pig. COOH-PLL is a promising CPA
      for further improvements in the vitrification of oocytes and embryos in mammalian
      species.

PMID- 28448637
TI  - 45S rDNA external transcribed spacer organization reveals new phylogenetic
      relationships in Avena genus.
AB  - The genus Avena comprises four distinct genomes organized in diploid (AA or CC),
      tetraploid (AABB or AACC) and hexaploid species (AACCDD), constituting an
      interesting model for phylogenetic analysis. The aim of this work was to
      characterize 45S rDNA intergenic spacer (IGS) variability in distinct species
      representative of Avena genome diversity-A. strigosa (AA), A. ventricosa (CvCv),
      A. eriantha (CpCp), A. barbata (AABB), A. murphyi (AACC), A. sativa (AACCDD) and
      A. sterilis (AACCDD) through the assessment of the 5' external transcribed spacer
      (5'-ETS), a promising IGS region for phylogenetic studies poorly studied in Avena
      genus. In this work, IGS length polymorphisms were detected mainly due to
      distinct 5'-ETS sequence types resulting from major differences in the number and
      organization of repeated motifs. Although species with A genome revealed a 5'-ETS
      organization (A-organization) similar to the one previously described in A.
      sativa, a distinct organization was unraveled in C genome diploid species (C
      organization). Interestingly, such new organization presents a higher similarity
      with other Poaceae species than A-genome sequences, supporting the hypothesis of
      C-genome being the ancestral Avena genome. Additionally, polyploid species with
      both genomes mainly retain the A-genome 5'-ETS organization, confirming the
      preferential elimination of C-genome sequences in Avena polyploid species.
      Moreover, 5'-ETS sequences phylogenetic analysis consistently clustered the
      species studied according to ploidy and genomic constitution supporting the use
      of ribosomal genes to highlight Avena species evolutive pathways.

PMID- 28448638
TI  - A minimal model of burst-noise induced bistability.
AB  - We investigate the influence of intrinsic noise on stable states of a one
      dimensional dynamical system that shows in its deterministic version a saddle
      node bifurcation between monostable and bistable behaviour. The system is a
      modified version of the Schlogl model, which is a chemical reaction system with
      only one type of molecule. The strength of the intrinsic noise is varied without
      changing the deterministic description by introducing bursts in the autocatalytic
      production step. We study the transitions between monostable and bistable
      behavior in this system by evaluating the number of maxima of the stationary
      probability distribution. We find that changing the size of bursts can destroy
      and even induce saddle-node bifurcations. This means that a bursty production of
      molecules can qualitatively change the dynamics of a chemical reaction system
      even when the deterministic description remains unchanged.

PMID- 28448640
TI  - Mapping of the Lassa virus LAMP1 binding site reveals unique determinants not
      shared by other old world arenaviruses.
AB  - Cell entry of many enveloped viruses occurs by engagement with cellular
      receptors, followed by internalization into endocytic compartments and pH-induced
      membrane fusion. A previously unnoticed step of receptor switching was found to
      be critical during cell entry of two devastating human pathogens: Ebola and Lassa
      viruses. Our recent studies revealed the functional role of receptor switching to
      LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of
      conserved histidines in this switching, suggesting that other viruses from this
      family may also switch to LAMP1. However, when we investigated viruses that are
      genetically close to Lassa virus, we discovered that they cannot bind LAMP1. A
      crystal structure of the receptor-binding module from Morogoro virus revealed
      structural differences that allowed mapping of the LAMP1 binding site to a unique
      set of Lassa residues not shared by other viruses in its family, illustrating a
      key difference in the cell-entry mechanism of Lassa virus that may contribute to
      its pathogenicity.

PMID- 28448639
TI  - Cryptic diversity of the subfamily Calaphidinae (Hemiptera: Aphididae) revealed
      by comprehensive DNA barcoding.
AB  - Aphids are a species rich group comprising many important pests. However, species
      identification can be very difficult for aphids due to their morphological
      ambiguity. DNA barcoding has been widely adopted for rapid and reliable species
      identification as well as cryptic species detection. In this study, we
      investigated cryptic diversity in the subfamily Calaphidinae (Hemiptera:
      Aphididae) based on 899 sequences of cytochrome c oxidase I (COI) for 115
      morphospecies (78 species collected in this study and sequences of 73 species
      downloaded from Genbank). Among these 115 morphospecies, DNA barcoding results of
      90 (78.3%) species were identical to results of morphological identification.
      However, 25 (21.7%) morphospecies showed discrepancies between DNA barcoding and
      traditional taxonomy. Among these 25 discordances, a total of 15 cryptic species
      were identified from 12 morphospecies. We also found three morphologically
      distinct species pairs that sharing DNA barcoding. Based on molecular operational
      taxonomic unit (MOTU) estimation, we discussed on species delimitation threshold
      value for these taxa. Our findings confirm that Calaphidinae has high cryptic
      diversity even though aphids are relatively well-studied.

PMID- 28448642
TI  - Inferior Survival Rates After Chemoradiation for Rectal Cancer Without Surgery.

PMID- 28448643
TI  - The 10 Commandments of Management for Acute Upper Airway Obstruction in Infants
      and Children.

PMID- 28448641
TI  - Detecting Glaucoma With a Portable Brain-Computer Interface for Objective
      Assessment of Visual Function Loss.
AB  - Importance: The current assessment of visual field loss in diseases such as
      glaucoma is affected by the subjectivity of patient responses and the lack of
      portability of standard perimeters. Objective: To describe the development and
      initial validation of a portable brain-computer interface (BCI) for objectively
      assessing visual function loss. Design, Setting, and Participants: This case
      control study involved 62 eyes of 33 patients with glaucoma and 30 eyes of 17
      healthy participants. Glaucoma was diagnosed based on a masked grading of optic
      disc stereophotographs. All participants underwent testing with a BCI device and
      standard automated perimetry (SAP) within 3 months. The BCI device integrates
      wearable, wireless, dry electroencephalogram and electrooculogram systems and a
      cellphone-based head-mounted display to enable the detection of multifocal steady
      state visual-evoked potentials associated with visual field stimulation. The
      performances of global and sectoral multifocal steady state visual-evoked
      potentials metrics to discriminate glaucomatous from healthy eyes were compared
      with global and sectoral SAP parameters. The repeatability of the BCI device
      measurements was assessed by collecting results of repeated testing in 20 eyes of
      10 participants with glaucoma for 3 sessions of measurements separated by weekly
      intervals. Main Outcomes and Measures: Receiver operating characteristic curves
      summarizing diagnostic accuracy. Intraclass correlation coefficients and
      coefficients of variation for assessing repeatability. Results: Among the 33
      participants with glaucoma, 19 (58%) were white, 12 (36%) were black, and 2 (6%)
      were Asian, while among the 17 participants with healthy eyes, 9 (53%) were
      white, 8 (47%) were black, and none were Asian. The receiver operating
      characteristic curve area for the global BCI multifocal steady state visual
      evoked potentials parameter was 0.92 (95% CI, 0.86-0.96), which was larger than
      for SAP mean deviation (area under the curve, 0.81; 95% CI, 0.72-0.90), SAP mean
      sensitivity (area under the curve, 0.80; 95% CI, 0.69-0.88; P = .03), and SAP
      pattern standard deviation (area under the curve, 0.77; 95% CI, 0.66-0.87; P =
      .01). No statistically significant differences were seen for the sectoral
      measurements between the BCI and SAP. Intraclass coefficients for global and
      sectoral parameters ranged from 0.74 to 0.92, and mean coefficients of variation
      ranged from 3.03% to 7.45%. Conclusions and Relevance: The BCI device may be
      useful for assessing the electrical brain responses associated with visual field
      stimulation. The device discriminated eyes with glaucomatous neuropathy from
      healthy eyes in a clinically based setting. Further studies should investigate
      the feasibility of the BCI device for home-based testing as well as for detecting
      visual function loss over time.

PMID- 28448644
TI  - With Experience Comes Wisdom.

PMID- 28448645
TI  - Estimating Survival After Salvage Surgery for Recurrent Oral Cavity Cancer.
AB  - Importance: Locoregional recurrence of oral cavity squamous cell carcinoma
      (OCSCC) continues to be a life-threatening and difficult clinical situation.
      Salvage surgery can result in significant morbidities, and survival following
      recurrence is poor. Objective: To outline prognostic factors influencing overall
      survival (OS) following salvage surgery for OCSCC to guide management of
      treatment for patients with locoregionally recurrent disease. Design, Setting,
      and Participants: The medical records of 293 patients presenting to the London
      Health Sciences Center with locoregionally recurrent OCSCC between October 5,
      1999, and May 2, 2011, were retrospectively reviewed. The primary outcome was OS
      from salvage treatment to last follow-up or death. Univariate analyses were
      carried out using the Cox proportional hazards regression model. A recursive
      partitioning analysis was used to create risk groups based on prognosis. Analysis
      was conducted from December 8, 2015, to February 26, 2016. Results: Of the 293
      patients evaluated, 59 (20%) had recurrence identified after their initial OCSCC
      treatment; 39 (66%) were men, and the mean (SD) age at diagnosis was 62.2 (11.8)
      years. Thirty-nine (66%) of these patients underwent salvage surgery for
      locoregional recurrence with curative intent. Five-year OS from the time of
      salvage surgery was 43%. Recursive partitioning analysis identified 3 risk
      groups: (1) high risk (patients who received adjuvant chemoradiotherapy or
      radiotherapy after initial surgery) with 5-year OS rate of 10% (hazard ratio
      [HR], 9.41; 95% CI, 2.68-33.04), (2) intermediate risk (previous surgery alone,
      age >=62 years) with a 5-year OS rate of 39% (HR, 2.95; 95% CI, 0.86-10.09), and
      (3) low risk (previous surgery alone, age <62 years) with 5-year OS rate of 74%.
      Conclusions and Relevance: This recursive partitioning analysis identified 3
      prognostic groups in patients undergoing salvage surgery for recurrent OCSCC. The
      marked differences in survival between these groups should be taken into
      consideration when counselling and managing treatment for patients with
      locoregionally recurrent disease.

PMID- 28448646
TI  - Diabetic Retinopathy and Antivascular Endothelial Growth Factor Agents.

PMID- 28448647
TI  - Exclusion of Eligible Indeterminate Thyroid Nodules in Estimates of Negative
      Predictive Value for the Gene Expression Classifier-Reply.

PMID- 28448648
TI  - A Day in the Life: NICU Medical Director Tends to Infants With Neonatal
      Abstinence Syndrome.

PMID- 28448649
TI  - Erroneous Sentence in Cancer Care Chronicles Article.

PMID- 28448650
TI  - Inferior Survival Rates After Chemoradiation for Rectal Cancer Without Surgery
      Reply.

PMID- 28448651
TI  - Sickness.

PMID- 28448652
TI  - Breaking the Rules for Better Care.

PMID- 28448653
TI  - Exclusion of Eligible Indeterminate Thyroid Nodules in Estimates of Negative
      Predictive Value for the Gene Expression Classifier.

PMID- 28448654
TI  - Frontal Sinus Lesion.

PMID- 28448656
TI  - Erroneous Sentence Removed From Article.

PMID- 28448655
TI  - Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a
      Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab.
AB  - Importance: Anti-vascular endothelial growth factor (anti-VEGF) therapy for
      diabetic macular edema (DME) favorably affects diabetic retinopathy (DR)
      improvement and worsening. It is unknown whether these effects differ across anti
      VEGF agents. Objective: To compare changes in DR severity during aflibercept,
      bevacizumab, or ranibizumab treatment for DME. Design, Setting, and Participants:
      Preplanned secondary analysis of data from a comparative effectiveness trial for
      center-involved DME was conducted in 650 participants receiving aflibercept,
      bevacizumab, or ranibizumab. Retinopathy improvement and worsening were
      determined during 2 years of treatment. Participants were randomized in 2012
      through 2013, and the trial concluded on September 23, 2015. Interventions:
      Random assignment to aflibercept, 2.0 mg; bevacizumab, 1.25 mg; ranibizumab, 0.3
      mg, up to every 4 weeks through 2 years following a retreatment protocol. Main
      Outcomes and Measures: Percentages with retinopathy improvement at 1 and 2 years
      and cumulative probabilities for retinopathy worsening through 2-year without
      adjustment for multiple outcomes. Results: A total of 650 participants (495
      [76.2%] nonproliferative DR [NPDR], 155 proliferative DR [PDR]) were analyzed;
      302 (46.5%) were women and mean (SD) age was 61 (10) years; 425 (65.4%) were
      white. At 1 year, among 423 NPDR eyes, 44 of 141 (31.2%) treated with
      aflibercept, 29 of 131 (22.1%) with bevacizumab, and 57 of 151 (37.7%) with
      ranibizumab had improvement of DR severity (adjusted difference: 11.7%; 95% CI,
      2.9% to 20.6%; P = .004 for aflibercept vs bevacizumab; 8.9%; 95% CI, 1.7% to
      16.1%; P = .01 for ranibizumab vs bevacizumab; and 2.9%; 95% CI, -5.7% to 11.4%;
      P = .51 for aflibercept vs ranibizumab). At 2 years, 33 eyes (24.8%) in the
      aflibercept group, 25 eyes (22.1%) in the bevacizumab group, and 40 eyes (31.0%)
      in the ranibizumab group had DR improvement; no treatment group differences were
      identified. For 93 eyes with PDR at baseline, 1-year improvement rates were 75.9%
      for aflibercept, 31.4% for bevacizumab, and 55.2% for ranibizumab (adjusted
      difference: 50.4%; 95% CI, 26.8% to 74.0%; P < .001 for aflibercept vs
      bevacizumab; 20.4%; 95% CI, -3.1% to 44.0%; P = .09 for ranibizumab vs
      bevacizumab; and 30.0%; 95% CI, 4.4% to 55.6%; P = .02 for aflibercept vs
      ranibizumab). These rates and treatment group differences appeared to be
      maintained at 2 years. Despite the reduced numbers of injections in the second
      year, 66 (59.5%) of NPDR and 28 (70.0%) of PDR eyes that manifested improvement
      at 1 year maintained improvement at 2 years. Two-year cumulative rates for
      retinopathy worsening ranged from 7.1% to 10.2% and 17.2% to 26.4% among anti
      VEGF groups for NPDR and PDR eyes, respectively. No statistically significant
      treatment differences were noted. Conclusions and Relevance: At 1 and 2 years,
      eyes with NPDR receiving anti-VEGF treatment for DME may experience improvement
      in DR severity. Less improvement was demonstrated with bevacizumab at 1 year than
      with aflibercept or ranibizumab. Aflibercept was associated with more improvement
      at 1 and 2 years in the smaller subgroup of participants with PDR at baseline.
      All 3 anti-VEGF treatments were associated with low rates of DR worsening. These
      data provide additional outcomes that might be considered when choosing an anti
      VEGF agent to treat DME.

PMID- 28448658
TI  - Understanding Neuroendocrine Tumors-A NET Gain.

PMID- 28448657
TI  - Association Between SLC16A5 Genetic Variation and Cisplatin-Induced Ototoxic
      Effects in Adult Patients With Testicular Cancer.
AB  - Importance: Cisplatin-induced ototoxic effects are an important complication that
      affects testicular cancer survivors as a consequence of treatment. The
      identification of genetic variants associated with this adverse drug reaction
      will further our mechanistic understanding of its development and potentially
      lead to strategies to prevent ototoxic effects. Objective: To identify the
      genetic variants associated with cisplatin-induced ototoxic effects in adult
      testicular cancer patients. Design, Setting, and Participants: This retrospective
      study was performed by the Canadian Pharmacogenomics Network for Drug Safety
      using patients recruited from 5 adult oncology treatment centers across Canada.
      Male patients who were 17 years or older, diagnosed with germ cell testicular
      cancer, and previously treated with cisplatin-based chemotherapy were recruited
      from July 2009 to April 2013 using active surveillance methodology. Cisplatin
      induced ototoxic effects were independently diagnosed by 2 audiologists. Patients
      were genotyped for 7907 variants using a custom pharmacogenomic array. Logistic
      regression was used to identify genetic variants that were significantly
      associated with ototoxic effects. The validity of these findings was confirmed
      through independent replication and cell-based functional assays. Exposures:
      Cisplatin-based chemotherapy. Main Outcomes and Measures: Cisplatin-induced
      ototoxic effects. Results: After exclusions, 188 patients (median [interquartile
      range] age, 31 [24-39] years) were enrolled in this study to form the discovery
      and replication cohorts. Association and fine-mapping analyses identified a
      protein-coding variant, rs4788863 in SLC16A5, that was associated with protection
      against cisplatin-induced ototoxic effects in 2 independent cohorts (combined
      cohort: odds ratio, 0.06; 95% CI, 0.02-0.22; P = 2.17 * 10-7). Functional
      validation of this transporter gene revealed that in vitro SLC16A5-silencing
      altered cellular responses to cisplatin treatment, supporting a role for SLC16A5
      in the development of cisplatin-induced ototoxic effects. These results were
      further supported by the literature, which provided confirmatory evidence for the
      role that SLC16A5 plays in hearing. Conclusions and Relevance: This study has
      identified a novel association between protein-coding variation in SLC16A5 and
      cisplatin-induced ototoxic effects. These findings have provided insight into the
      molecular mechanisms of this adverse drug reaction in adult patients with germ
      cell testicular cancer. Given that previous studies have shown that cimetidine,
      an SLC16A5-inhibitor, prevents murine cisplatin-induced ototoxic effects, the
      findings from this study have important implications for otoprotectant strategies
      in humans.

PMID- 28448660
TI  - Combining local and global limitations of visual search.
AB  - There are different opinions about the roles of local interactions and central
      processing capacity in visual search. This study attempts to clarify the problem
      using a new version of relevant set cueing. A central precue indicates two
      symmetrical segments (that may contain a target object) within a circular array
      of objects presented briefly around the fixation point. The number of objects in
      the relevant segments, and density of objects in the array were varied
      independently. Three types of search experiments were run: (a) search for a
      simple visual feature (color, size, and orientation); (b) conjunctions of simple
      features; and (c) spatial configuration of simple features (rotated Ts). For
      spatial configuration stimuli, the results were consistent with a fixed global
      processing capacity and standard crowding zones. For simple features and their
      conjunctions, the results were different, dependent on the features involved.
      While color search exhibits virtually no capacity limits or crowding, search for
      an orientation target was limited by both. Results for conjunctions of features
      can be partly explained by the results from the respective features. This study
      shows that visual search is limited by both local interference and global
      capacity, and the limitations are different for different visual features.

PMID- 28448661
TI  - Pigmented Iridociliary Lesion and Increased Intraocular Pressure.

PMID- 28448659
TI  - Evaluation of Ecological Momentary Assessment for Tinnitus Severity.
AB  - Importance: Existing patient-reported outcome measures of tinnitus assess the
      severity and disability retrospectively, which may result in adequate
      reliability, but cannot capture the fluctuating and individualized nature of
      tinnitus. Experience sampling may provide an alternative. Objective: To use an
      ecological momentary assessment (EMA) to measure tinnitus disability and
      associated constructs. Design, Setting, and Participants: Forty adults with
      tinnitus provided self-report of their tinnitus bother using 5 questions measured
      by EMA, as well as standard retrospective outcome measures. In this 6-week
      longitudinal observational study conducted from July 15 to December 22, 2014,
      participants provided EMA data for 2 weeks (part 1); then after a 2-week break,
      they provided EMA data for an additional 2 weeks (part 2). A text message with a
      link to the EMA survey was sent for a total of 56 assessments during each 2-week
      assessment period. Ecological momentary assessment responses were evaluated using
      multilevel confirmatory factor analysis to assess the fluctuating nature of
      bothersome tinnitus across the group and within the pool of individuals over
      time. Main Outcomes and Measures: Ecological momentary assessment questions
      measured tinnitus disability and associated constructs. Compliance in each study
      part was assessed based on response rates. The Tinnitus Functional Index and the
      Overall Global Rating of Bother Scale were assessed at the beginning and end of
      each 2-week assessment period to explore the effect of the frequent EMAs on the
      perceived level of bother from tinnitus. Results: Of the 40 participants in the
      study (10 women and 30 men; mean [SD] age, 60.0 [10.5] years), the median survey
      response rate was high (49 responses to 56 surveys sent [88%] for part 1 and 47
      responses of 56 surveys sent [84%] for part 2). The latent factor identified by
      the 2-level confirmatory factor analysis models demonstrates that within
      individual tinnitus bother, loudness, and stress vary together over time. In
      addition, tinnitus bother, feeling, and stress symptoms all vary together across
      individuals, which means that bother and stress covary strongly both across time
      and across individuals. Conclusions and Relevance: Ecological momentary
      assessment evaluates the moment-to-moment perception of tinnitus and the effect
      of emotional and environmental factors, which suggests that it is a superior tool
      to measure tinnitus outcomes compared with standard retrospective self-reports.
      Taken together, information from emotional and environmental factors can be
      summarized in an underlying (latent) factor that represents a vulnerability to
      bothersome tinnitus and that can be used to comprehensively describe the tinnitus
      experience. Momentary variability in tinnitus bother is strongly associated with
      levels of perceived stress.

PMID- 28448663
TI  - PRAME as a Potential Target for Immunotherapy in Metastatic Uveal Melanoma.
AB  - Importance: Uveal melanoma (UM) is an intraocular primary malignant neoplasm that
      often gives rise to metastatic disease for which there are no effective
      therapies. A substantial proportion of UMs express the cancer-testis antigen
      PRAME (preferentially expressed antigen in melanoma), which can potentially be
      targeted by adoptive T-cell therapy. Objective: To determine whether there may be
      a rationale for PRAME-directed T-cell therapy for metastatic UM. Design, Setting,
      and Participants: An experimental study using a retrospective cohort of 64
      patients with UM (median follow-up, 62 months) was conducted from January 8,
      2015, to November 20, 2016, at the Leiden University Medical Center. Clinical,
      histopathologic, and genetic parameters were compared between 64 PRAME-positive
      and PRAME-negative UMs. HLA class I restricted, PRAME-specific T cells were
      stimulated with UM cell lines to measure their antigen-specific reactivity
      against these cell lines, which were analyzed for PRAME expression by real-time
      quantitative polymerase chain reaction. Uveal melanoma metastases from 16
      unrelated patients were assessed for PRAME expression by messenger RNA
      fluorescence in situ hybridization and for HLA class I expression by
      immunofluorescence staining. Main Outcomes and Measures: Interferon gamma
      production for antigen-specific reactivity and detection of PRAME and HLA class I
      expression in primary and metastatic UM. Results: Of the 64 patients in the study
      (31 women and 33 men; mean [SD] age at the time of enucleation, 60.6 [15.6]
      years), PRAME expression was negative in 35 primary UMs and positive in 29
      primary UMs. Positive PRAME expression was associated with a high largest basal
      diameter (15.0 vs 12.0 mm; P = .005), ciliary body involvement (59% vs 26%; P =
      .008), and amplification of chromosome 8q (66% vs 23%; P = .002). PRAME-specific
      T cells reacted against 4 of 7 UM cell lines, demonstrating that T-cell
      reactivity correlated with PRAME expression. Metastatic UM samples were positive
      for PRAME messenger RNA in 11 of 16 patients and for HLA class I in 10 of 16
      patients, with 8 of 16 patients demonstrating coexpression of both PRAME and HLA
      class I. Conclusions and Relevance: PRAME is expressed in many primary and
      metastatic UMs, and about half of the metastatic UMs coexpress PRAME and HLA
      class I. The finding that PRAME-specific T cells in this study reacted against
      PRAME-positive UM cell lines suggests a potential role for PRAME-directed
      immunotherapy for selected patients with metastatic UM.

PMID- 28448662
TI  - Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in
      Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The
      AIO-FLOT3 Trial.
AB  - Importance: Surgical resection has a potential benefit for patients with
      metastatic adenocarcinoma of the stomach and gastroesophageal junction.
      Objective: To evaluate outcome in patients with limited metastatic disease who
      receive chemotherapy first and proceed to surgical resection. Design, Setting,
      and Participants: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie
      fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective,
      phase 2 trial of 252 patients with resectable or metastatic gastric or
      gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer
      care centers in Germany between February 1, 2009, and January 31, 2010, and
      stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or
      extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was
      performed in March 2013. Interventions: Patients in arm A received 4 preoperative
      cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by
      surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles
      of neoadjuvant FLOT and proceeded to surgical resection if restaging (using
      computed tomography and magnetic resonance imaging) showed a chance of margin
      free (R0) resection of the primary tumor and at least a macroscopic complete
      resection of the metastatic lesions. Patients in arm C were offered FLOT
      chemotherapy and surgery only if required for palliation. Patients received a
      median (range) of 8 (1-15) cycles of FLOT. Main Outcomes and Measures: The
      primary end point was overall survival. Results: In total, 238 of 252 patients
      (94.4%) were eligible to participate. The median (range) age of participants was
      66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65
      (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only
      retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11
      [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4
      [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9
      months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7
      months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P <
      .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which
      is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded
      to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level
      not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1
      22.9) for the other patients. Conclusions and Relevance: Patients with limited
      metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery
      showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further
      randomized clinical trials. Trial Registration: clinicaltrials.gov identifier:
      NCT00849615.

PMID- 28448664
TI  - Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of
      Prematurity: A Phase 1 Dosing Study.
AB  - Importance: Intravitreous bevacizumab (0.25 to 0.625 mg) is increasingly used to
      treat type 1 retinopathy of prematurity (ROP), but there remain concerns about
      systemic toxicity. A much lower dose may be effective while reducing systemic
      risk. Objective: To find a dose of intravitreous bevacizumab that was lower than
      previously used for severe ROP, was effective in this study, and could be tested
      in future larger studies. Design, Setting, and Participants: Between May 2015 and
      September 2016, 61 premature infants with type 1 ROP in 1 or both eyes were
      enrolled in a masked, multicenter, phase 1 dose de-escalation study. One eye of
      10 to 14 infants received 0.25 mg of intravitreous bevacizumab. If successful,
      the dose was reduced for the next group of infants (to 0.125 mg, then 0.063 mg,
      and finally 0.031 mg). Diluted bevacizumab was delivered using 300 uL syringes
      with 5/16-inch, 30-gauge fixed needles. Interventions: Bevacizumab injections at
      0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg. Main Outcomes and Measures: Success
      was defined as improvement in preinjection plus disease or zone I stage 3 ROP by
      5 days after injection or sooner, and no recurrence of type 1 ROP or severe
      neovascularization requiring additional treatment within 4 weeks. Results: Fifty
      eight of 61 enrolled infants had 4-week outcomes completed; mean birth weight was
      709 g and mean gestational age was 24.9 weeks. Success was achieved in 11 of 11
      eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9
      eyes at 0.031 mg. Conclusions and Relevance: A dose of bevacizumab as low as
      0.031 mg was effective in 9 of 9 eyes in this phase 1 study and warrants further
      investigation. Identifying a lower effective dose of bevacizumab may reduce the
      risk for neurodevelopmental disability or detrimental effects on other organs.

PMID- 28448665
TI  - Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With
      Neuroendocrine Tumors in the United States.
AB  - Importance: The incidence and prevalence of neuroendocrine tumors (NETs) are
      thought to be rising, but updated epidemiologic data are lacking. Objective: To
      explore the evolving epidemiology and investigate the effect of therapeutic
      advances on survival of patients with NETs. Design, Setting, and Participants: A
      retrospective, population-based study using nationally representative data from
      the Surveillance, Epidemiology, and End Results (SEER) program was conducted to
      evaluate 64 971 patients with NETs from 1973 to 2012. Associated population data
      were used to determine annual age-adjusted incidence, limited-duration
      prevalence, and 5-year overall survival (OS) rates. Trends in survival from 2000
      to 2012 were evaluated for the entire cohort as well as specific subgroups,
      including distant-stage gastrointestinal NETs and pancreatic NETs. Analyses were
      conducted between December 2015, and February 2017. Main Outcomes and Measures:
      Neuroendocrine tumor incidence, prevalence, and OS rates. Results: Of the 64 971
      cases of NETs, 34 233 (52.7%) were women. The age-adjusted incidence rate
      increased 6.4-fold from 1973 (1.09 per 100 000) to 2012 (6.98 per 100 000). This
      increase occurred across all sites, stages, and grades. In the SEER 18 registry
      grouping (2000-2012), the highest incidence rates were 1.49 per 100 000 in the
      lung, 3.56 per 100 000 in gastroenteropancreatic sites, and 0.84 per 100 000 in
      NETs with an unknown primary site. The estimated 20-year limited-duration
      prevalence of NETs in the United States on January 1, 2014, was 171 321. On
      multivariable analyses, the median 5-year OS rate varied significantly by stage,
      grade, age at diagnosis, primary site, and time period of diagnosis. The OS rate
      for all NETs improved from the 2000-2004 period to the 2009-2012 period (hazard
      ratio [HR], 0.79; 95% CI, 0.73-0.85). Even larger increases in OS between these
      periods were noted in distant-stage gastrointestinal NETs (HR, 0.71; 95% CI, 0.62
      0.81) and distant-stage pancreatic NETs (HR, 0.56; 95% CI, 0.44-0.70).
      Conclusions and Relevance: The incidence and prevalence of NETs are steadily
      rising, possibly owing to detection of early-stage disease and stage migration.
      Survival for all NETs has improved over time, especially for distant-stage
      gastrointestinal NETs and pancreatic NETs in particular, reflecting improvement
      in therapies. These data will help to prioritize future research directions.

PMID- 28448666
TI  - Emerging Goals in Aesthetic Medicine.

PMID- 28448668
TI  - Prognostic Indication of Sarcopenia for Wound Complication After Total
      Laryngectomy.

PMID- 28448667
TI  - Association Between Facial Rejuvenation and Observer Ratings of Youth,
      Attractiveness, Success, and Health.
AB  - Importance: Surgical procedures for the aging face-including face-lift,
      blepharoplasty, and brow-lift-consistently rank among the most popular cosmetic
      services sought by patients. Although these surgical procedures are broadly
      classified as procedures that restore a youthful appearance, they may improve
      societal perceptions of attractiveness, success, and health, conferring an even
      larger social benefit than just restoring a youthful appearance to the face.
      Objectives: To determine if face-lift and upper facial rejuvenation surgery
      improve observer ratings of age, attractiveness, success, and health and to
      quantify the effect of facial rejuvenation surgery on each individual domain.
      Design, Setting, and Participants: A randomized clinical experiment was performed
      from August 30 to September 18, 2016, using web-based surveys featuring
      photographs of patients before and after facial rejuvenation surgery. Observers
      were randomly shown independent images of the 12 patients; within a given survey,
      observers saw either the preoperative or postoperative photograph of each patient
      to reduce the possibility of priming. Observers evaluated patient age using a
      slider bar ranging from 30 to 80 years that could be moved up or down in 1-year
      increments, and they ranked perceived attractiveness, success, and health using a
      100-point visual analog scale. The bar on the 100-point scale began at 50; moving
      the bar to the right corresponded to a more positive rating in these measures and
      moving the bar to the left, a more negative rating. Main Outcomes and Measures: A
      multivariate mixed-effects regression model was used to understand the effect of
      face-lift and upper facial rejuvenation surgery on observer perceptions while
      accounting for individual biases of the participants. Ordinal rank change was
      calculated to understand the clinical effect size of changes across the various
      domains after surgery. Results: A total of 504 participants (333 women, 165 men,
      and 6 unspecified; mean age, 29 [range, 18-70] years) successfully completed the
      survey. A multivariate mixed-effects regression model revealed a statistically
      significant change in age (-4.61 years; 95% CI, -4.97 to -4.25) and
      attractiveness (6.72; 95% CI, 5.96-7.47) following facial rejuvenation surgery.
      Observer-perceived success (3.85; 95% CI, 3.12-4.57) and health (7.65; 95% CI;
      6.87-8.42) also increased significantly as a result of facial rejuvenation
      surgery. Conclusions and Relevance: The data presented in this study demonstrate
      that patients are perceived as younger and more attractive by the casual observer
      after undergoing face-lift and upper facial rejuvenation surgery. These
      procedures also improved ratings of perceived success and health in our patient
      population. These findings suggest that facial rejuvenation surgery conveys an
      even larger societal benefit than merely restoring a youthful appearance to the
      face. Level of Evidence: NA.

PMID- 28448669
TI  - Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care.
AB  - Importance: Age-related macular degeneration (AMD) is the leading cause of
      irreversible vision impairment in older adults in the United States, yet little
      is known about whether AMD is appropriately diagnosed in primary eye care.
      Objectives: To examine the prevalence of eyes with AMD in patients seen in
      primary eye care clinics who purportedly have normal macular health per their
      medical record and the association of AMD with patient and physician
      characteristics. Design, Setting, and Participants: In this cross-sectional study
      of primary eye care practices in Birmingham, Alabama, 644 persons 60 years or
      older with normal macular health per medical record based on their most recent
      dilated comprehensive eye examination by a primary eye care ophthalmologist or
      optometrist were enrolled from May 1, 2009, through December 31, 2011. Data
      analysis was performed from May 1, 2016, through December 20, 2016. Main Outcomes
      and Measures: Presence of AMD as defined by the Clinical Age-Related Maculopathy
      Staging system based on color fundus photography and a masked grader. Types of
      AMD-associated lesions were noted. Patient health and physician characteristics
      were collected. Results: The sample consisted of 1288 eyes from 644 participants
      (231 [35.9%] male and 413 [64.1%] female; mean [SD] age, 69.4 [6.1] years; 611
      white [94.9%]) seen by 31 primary eye care ophthalmologists or optometrists. A
      total of 968 eyes (75.2%) had no AMD, in agreement with their medical record; 320
      (24.8%) had AMD despite no diagnosis of AMD in the medical record. Among eyes
      with undiagnosed AMD, 32 (10.0%) had hyperpigmentation, 43 (13.4%) had
      hypopigmentation, 249 (77.8%) had small drusen, 250 (78.1%) had intermediate
      drusen, and 96 (30.0%) had large drusen. Undiagnosed AMD was associated with
      older patient age (odds ratio [OR], 1.06; 95% CI, 1.04-1.09; P < .001), male sex
      (age-adjusted OR, 1.39; 95% CI, 1.02-1.91; P = .04), and less than a high school
      education (age-adjusted OR, 2.40; 95% CI, 1.03-5.62; P = .04). Prevalence of
      undiagnosed AMD was not different for ophthalmologists and optometrists (age
      adjusted OR, 0.99; 95% CI, 0.71-1.36; P = .94). Conclusions and Relevance:
      Approximately 25.0% of eyes deemed to be normal based on dilated eye examination
      by primary eye care physicians had macular characteristics that indicated AMD
      revealed by fundus photography and trained raters. A total of 30.0% of eyes with
      undiagnosed AMD had AMD with large drusen that would have been treatable with
      nutritional supplements had it been diagnosed. Improved AMD detection strategies
      may be needed in primary eye care as more effective treatment strategies for
      early AMD become available in the coming years.

PMID- 28448670
TI  - Molecular Mechanisms Underlying the Filtration Bleb-Maintaining Effects of
      Suberoylanilide Hydroxamic Acid (SAHA).
AB  - Purpose: Suberoylanilide hydroxamic acid (SAHA) has been shown to support the
      maintenance of experimental filtration blebs in animal models. This study was
      performed to investigate the molecular mechanisms underlying the bleb-maintaining
      effects of SAHA in modulating wound healing activities of conjunctival
      fibroblasts. Methods: Human conjunctival fibroblasts (HConFs) were pretreated
      with SAHA before treatment with TGF-beta2. Microarray-based screening was used to
      investigate the gene expression profiles. Gene ontology (GO) analysis was
      conducted to categorize the gene functions. The expression of TGF-beta-induced
      signaling molecules, alpha-smooth muscle actin, and extracellular matrix (ECM)
      proteins were evaluated by Western blot analyses. Multiplex immunoassay was
      performed to evaluate supernatant cytokine concentrations. Tube formation assay
      was used to evaluate angiogenesis using human umbilical vein endothelial cells.
      Results: GO analysis showed that SAHA, in the presence of TGF-beta2, induced
      changes in expression of genes involved in the TGF-beta receptor signaling
      pathway, cell proliferation, extracellular matrix organization, inflammatory
      responses, and angiogenesis. Subsequent in vitro experiments showed that SAHA
      partly inhibited the phosphorylation of Smad2, Smad3, and Akt. SAHA pretreatment
      potently suppressed TGF-beta2-driven cell proliferation, myofibroblast
      differentiation, contraction, ECM production, and angiogenic cytokine expression.
      The supernatant of HConFs treated with SAHA inhibited tube formation.
      Conclusions: SAHA has been shown to suppress angiogenesis and activation of
      conjunctival fibroblasts partly via inhibition of Smad and non-Smad TGF-beta
      signaling. This in vitro study provides new evidence for the molecular basis of
      the potential bleb-maintaining effects of SAHA, a novel candidate drug in
      modulating scar formation after glaucoma filtration surgery.

PMID- 28448671
TI  - Disrupted Eye Movements in Preperimetric Primary Open-Angle Glaucoma.
AB  - Purpose: Primary open-angle glaucoma (POAG) can be associated with abnormal
      ocular motor behavior, possibly as a compensatory strategy following visual field
      loss. The aim of this study was to explore the characteristics of saccadic eye
      movements in patients with early-stage POAG without any detectable glaucomatous
      visual field loss (i.e., preperimetric POAG). Methods: Binocular eye movements
      were explored in 16 patients with bilateral preperimetric POAG and 16 age-matched
      healthy controls in a cross-sectional, observational study. Visually guided
      horizontal prosaccades (5 degrees , 10 degrees , 15 degrees , and 20 degrees 
      amplitude) and antisaccades (12 degrees  amplitude) were measured using infrared
      oculography. The latency, average and peak velocities, amplitude and gain of
      prosaccades as well as the percentage of errors in the antisaccades task were
      compared between groups. Results: POAG patients exhibited a reduced average
      velocity of saccades compared to controls across all amplitudes of peripheral
      visual target presentation (P = 0.03). Saccades performed by POAG patients were
      hypometric, and with reduced amplitude (P = 0.007) and gain (P = 0.01) compared
      to controls. On average, POAG patients displayed more antisaccade errors (40.6%),
      as compared to controls (23.4%; P = 0.04). Conclusions: Here, we show that
      patients with POAG without detectable glaucomatous visual field loss exhibit
      altered saccadic eye movements. These abnormalities may indicate disordered
      cortical and subcortical saccadic regulation, either on the basis of subthreshold
      visual impairment, or as a result of wider disease-associated neurodegeneration.
      Additional studies, controlling for glaucoma medications, are required to
      delineate the neural basis of eye movement abnormalities associated with POAG.

PMID- 28448672
TI  - Correlation Between the Inflammatory Marker HLA-DR and Signs and Symptoms in
      Moderate to Severe Dry Eye Disease.
AB  - Purpose: To investigate correlations of the inflammatory HLA-DR marker with
      clinical signs and symptoms commonly used to assess dry eye disease (DED)
      severity. Methods: Baseline data were collected from three clinical studies
      conducted on moderate to severe DED patients. Characteristics of DED were
      analyzed and correlations were performed in 311 patients. Data were analyzed
      after treatment with 1 mg/mL cyclosporine (CsA) and vehicle. We quantified HLA-DR
      by flow cytometry in impression cytology specimens. Results: We found HLA-DR
      significantly increased with diagnosis of Sjogren syndrome (P < 0.0001) and
      meibomian gland disease (P = 0.0223). The strongest significant correlation was
      seen with the corneal fluorescein staining (CFS, r = 0.30, P < 0.0001).
      Significant negative relationships were also found with Schirmer's test (r = 
      0.20, P = 0.0003) and tear break-up time (TBUT, r = -0.13, P = 0.0226).
      Correlations were statistically significant with total Ocular Surface Disease
      Index and visual analog scale scores (r = 0.12, P = 0.0426, and r = 0.14, P=
      0.0176, respectively). We found HLA-DR arbitrary units of fluorescence were
      statistically reduced after CsA treatment compared to vehicle (P = 0.022 and P =
      0.021 in two studies). Conclusions: In clinical research on DED, discrepancy is
      often observed between symptoms and signs. We found HLA-DR correlated
      significantly with CFS clinical signs and to a lower extent Schirmer's test and
      weakly with TBUT and symptom reporting questionnaires. HLA-DR was reported to be
      useful for monitoring anti-inflammatory efficacy treatments in DED, which was
      confirmed with the reduction of HLA-DR while on CsA treatment. Its expression by
      conjunctival cells has the potential to serve as a biomarker, bridging signs and
      symptoms in clinical research in DED, but there is still a need for additional
      validation studies.

PMID- 28448673
TI  - Network for Investigation of Delirium Across the U.S. (NIDUS): Advancing the
      Field of Delirium with a New Interdisciplinary Research Network.

PMID- 28448676
TI  - "I'm Still Here": Personhood and the Early-Onset Dementia Experience.
AB  - Early-onset dementia (EOD) occurs before age 65. The current study examined the
      lived experience from the point of view of four adults younger than 65 with
      dementia, particularly how they perceive their personhood. Using interpretative
      phenomenological analysis as the research approach, findings revealed that the
      EOD experience can be incorporated into six themes: (a) A Personal Journey, (b)
      Navigating the System, (c) The Stigma of Dementia, (d) Connecting to the World,
      (e) A Story Worth Telling, and (f) I'm Still Here. Participants' stories, as
      presented via these six thematic threads, reveal that individuals with EOD can
      have a strong sense of personhood. Findings are discussed and situated within the
      current EOD body of knowledge, and new knowledge is presented. Implications for
      practice and recommendations for future research are discussed. [Journal of
      Gerontological Nursing, 43 (5), 12-17.].

PMID- 28448678
TI  - Slow Medicine: The Barrier on the Bridge.

PMID- 28448679
TI  - Who We Are, What We Believe: Getting to Geriatrics With a Capital "G" at #AGS17.

PMID- 28448680
TI  - 22q11.2 deletion syndrome lowers seizure threshold in adult patients without
      epilepsy.
AB  - OBJECTIVE: Previous studies examining seizures in patients with 22q11.2 deletion
      syndrome (22q11.2DS) have focused primarily on children and adolescents. In this
      study we investigated the prevalence and characteristics of seizures and epilepsy
      in an adult 22q11.2DS population. METHODS: The medical records of 202 adult
      patients with 22q11.2DS were retrospectively reviewed for documentation of
      seizures, electroencephalography (EEG) reports, and magnetic resonance imaging
      (MRI) findings. Epilepsy status was assigned in accordance with 2010
      International League Against Epilepsy Classification. RESULTS: Of 202 patients,
      32 (15.8%) had a documented history of seizure. Of these 32, 23 (71.8%) had acute
      symptomatic seizures, usually associated with hypocalcemia and/or antipsychotic
      or antidepressant use. Nine patients (9/32, 28%; 9/202, 4%) met diagnostic
      criteria for epilepsy. Two patients had genetic generalized epilepsy; two
      patients had focal seizures of unknown etiology; two had epilepsy due to
      malformations of cortical development; in two the epilepsy was due to acquired
      structural changes; and in one patient the epilepsy could not be further
      classified. SIGNIFICANCE: Similarly to children, the prevalence of epilepsy and
      acute symptomatic seizures in adults with 22q11.2DS is higher than in the general
      population. Hypocalcemia continues to be a risk factor for adults, but
      differently from kids, the main cause of seizures in adults with 22q11.2DS is
      exposure to antipsychotics and antidepressants. Further prospective studies are
      warranted to investigate how 22q11.2 microdeletion leads to an overall decreased
      seizure threshold.

PMID- 28448681
TI  - Autism: Too eager to learn? Event related potential findings of increased
      dependency on intentional learning in a serial reaction time task.
AB  - It has been suggested that people with autism spectrum disorder (ASD) have an
      increased tendency to use explicit (or intentional) learning strategies. This
      altered learning may play a role in the development of the social communication
      difficulties characterizing ASD. In the current study, we investigated incidental
      and intentional sequence learning using a Serial Reaction Time (SRT) task in an
      adult ASD population. Response times and event related potentials (ERP)
      components (N2b and P3) were assessed as indicators of learning and knowledge.
      Findings showed that behaviorally, sequence learning and ensuing explicit
      knowledge were similar in ASD and typically developing (TD) controls. However,
      ERP findings showed that learning in the TD group was characterized by an
      enhanced N2b, while learning in the ASD group was characterized by an enhanced
      P3. These findings suggest that learning in the TD group might be more incidental
      in nature, whereas learning in the ASD group is more intentional or effortful.
      Increased intentional learning might serve as a strategy for individuals with ASD
      to control an overwhelming environment. Although this led to similar behavioral
      performances on the SRT task, it is very plausible that this intentional learning
      has adverse effects in more complex social situations, and hence contributes to
      the social impairments found in ASD. Autism Res 2017, 10: 1533-1543. (c) 2017
      International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 28448682
TI  - Validation of the Behavioural Observation Scale 3 for the evaluation of pain in
      adults.
AB  - BACKGROUND: Many behavioural scales are available to assess pain but none are
      suitable for a quick evaluation of non-sedated and non-geriatric adults. The
      Behavioural Observation Scale 3 (BOS-3) is short, composed of five items. This
      study examined its feasibility and diagnostic performances. METHODS: Adult
      patients were included from medical and surgical departments of the University
      Hospital of Bordeaux. In a cross-sectional study, BOS-3 was compared to Numerical
      Rate Scale (NRS) with communicating patients (CP) and Behavioural Scale for the
      Elderly Person (ECPA2) with non-communicating patients (NCP). Each time, BOS-3
      and reference scale were performed by an internal caregiver and an external
      expert. RESULTS: We included 447 patients: 395 communicating and 52 non
      communicating. All patients were assessed by the BOS-3 and the reference test.
      All BOS-3 were carried out in less than one minute with only four missing data.
      Its reproducibility (ICC = 0.77 [95% CI 0.73-0.81] with CP and 0.93 [95% CI 0.89
      0.97] with NCP) and its internal consistency (Cronbach alpha = 0.67 with CP and
      0.70 with NCP) were good. In non-communicating patients, ROC analysis set a
      threshold at 3 on 10. Sensitivity was 0.87 [95% CI 0.77-0.96], specificity 0.97
      [95% CI 0.93-1.00], positive predictive value 0.93 [95% CI 0.86-0.99] and
      negative predictive value 0.95 [95% CI 0.89-1.00]. In communicating patients,
      sensitivity decreased to 0.34 [95% CI 0.28-0.38] but specificity reached 0.96
      [95% CI 0.94-0.98] and positive predictive value 0.75 [95% CI 0.70-0.79].
      CONCLUSIONS: BOS-3 had good metrological properties in non-communicating adults.
      With communicating patients, a positive BOS-3 could be an additional tool to
      confirm pain, when underestimated on the NRS. SIGNIFICANCE: This study describes
      the diagnostic performances of a behavioral pain assessment scale designed for
      non-geriatric and non-sedated adults. The results show its validity in non
      communicating patients and suggest its usefulness as an ancillary tool in
      communicating patients in whom simple numerical scales are often insufficient.

PMID- 28448683
TI  - Magnetic resonance imaging connectivity for the prediction of seizure outcome in
      temporal lobe epilepsy.
AB  - OBJECTIVE: Currently, approximately 60-70% of patients with unilateral temporal
      lobe epilepsy (TLE) remain seizure-free 3 years after surgery. The goal of this
      work was to develop a presurgical connectivity-based biomarker to identify those
      patients who will have an unfavorable seizure outcome 1-year postsurgery.
      METHODS: Resting-state functional and diffusion-weighted 3T magnetic resonance
      imaging (MRI) was acquired from 22 unilateral (15 right, 7 left) patients with
      TLE and 35 healthy controls. A seizure propagation network was identified
      including ipsilateral (to seizure focus) and contralateral hippocampus, thalamus,
      and insula, with bilateral midcingulate and precuneus. Between each pair of
      regions, functional connectivity based on correlations of low frequency
      functional MRI signals, and structural connectivity based on streamline density
      of diffusion MRI data were computed and transformed to metrics related to healthy
      controls of the same age. RESULTS: A consistent connectivity pattern representing
      the network expected in patients with seizure-free outcome was identified using
      eight patients who were seizure-free at 1-year postsurgery. The hypothesis that
      increased similarity to the model would be associated with better seizure outcome
      was tested in 14 other patients (Engel class IA, seizure-free: n = 5; Engel class
      IB-II, favorable: n = 4; Engel class III-IV, unfavorable: n = 5) using two
      similarity metrics: Pearson correlation and Euclidean distance. The seizure-free
      connectivity model successfully separated all the patients with unfavorable
      outcome from the seizure-free and favorable outcome patients (p = 0.0005, two
      tailed Fisher's exact test) through the combination of the two similarity metrics
      with 100% accuracy. No other clinical and demographic predictors were successful
      in this regard. SIGNIFICANCE: This work introduces a methodologic framework to
      assess individual patients, and demonstrates the ability to use network
      connectivity as a potential clinical tool for epilepsy surgery outcome prediction
      after more comprehensive validation.

PMID- 28448684
TI  - Statistical modeling for Bayesian extrapolation of adult clinical trial
      information in pediatric drug evaluation.
AB  - Children represent a large underserved population of "therapeutic orphans," as an
      estimated 80% of children are treated off-label. However, pediatric drug
      development often faces substantial challenges, including economic, logistical,
      technical, and ethical barriers, among others. Among many efforts trying to
      remove these barriers, increased recent attention has been paid to extrapolation;
      that is, the leveraging of available data from adults or older age groups to draw
      conclusions for the pediatric population. The Bayesian statistical paradigm is
      natural in this setting, as it permits the combining (or "borrowing") of
      information across disparate sources, such as the adult and pediatric data. In
      this paper, authored by the pediatric subteam of the Drug Information Association
      Bayesian Scientific Working Group and Adaptive Design Working Group, we develop,
      illustrate, and provide suggestions on Bayesian statistical methods that could be
      used to design improved pediatric development programs that use all available
      information in the most efficient manner. A variety of relevant Bayesian
      approaches are described, several of which are illustrated through 2 case
      studies: extrapolating adult efficacy data to expand the labeling for Remicade to
      include pediatric ulcerative colitis and extrapolating adult exposure-response
      information for antiepileptic drugs to pediatrics.

PMID- 28448685
TI  - Adult neurobehavioral alterations in male and female mice following developmental
      exposure to paracetamol (acetaminophen): characterization of a critical period.
AB  - Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic
      and antipyretic properties. Among pregnant women and young children, paracetamol
      is one of the most frequently used drugs and is considered the first-choice
      treatment for pain and/or fever. Recent findings in both human and animal studies
      have shown associations between paracetamol intake during brain development and
      adverse behavioral outcomes later in life. The present study was undertaken to
      investigate if the induction of these effects depend on when the exposure occurs
      during a critical period of brain development and if male and female mice are
      equally affected. Mice of both sexes were exposed to two doses of paracetamol (30
      + 30 mg kg-1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous
      behavior, when introduced to a new home environment, was observed at the age of 2
      months. We show that adverse effects on adult behavior and cognitive function
      occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but
      not when exposed on PND 19. These neurodevelopmental time points in mice
      correspond to the beginning of the third trimester of pregnancy and the time
      around birth in humans, supporting existing human data. Considering that
      paracetamol is the first choice treatment for pain and/or fever during pregnancy
      and early life, these results may be of great importance for future research and,
      ultimately, for clinical practice. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28448687
TI  - Postexercise blood flow restriction does not enhance muscle hypertrophy induced
      by multiple-set high-load resistance exercise.
AB  - To test the applicability of postexercise blood flow restriction (PEBFR) in
      practical training programmes, we investigated whether PEBFR enhances muscle
      hypertrophy induced by multiple-set high-load resistance exercise (RE). Seven men
      completed an eight-week RE programme for knee extensor muscles. Employing a
      within-subject design, one leg was subjected to RE + PEBFR, whereas contralateral
      leg to RE only. On each exercise session, participants performed three sets of
      unilateral knee extension exercise at approximately 70% of their one-repetition
      maximum for RE leg first, and then performed three sets for RE + PEBFR leg.
      Immediately after completion of the third set, the proximal portion of the RE +
      PEBFR leg was compressed with an air-pressure cuff for 5 min at a pressure
      ranging from 100 to 150 mmHg. If participants could perform 10 repetitions for
      three sets in two consecutive exercise sessions, the work load was increased by
      5% at the next exercise session. Muscle thickness and strength of knee extensor
      muscles were measured before and after the eight-week training period and after
      the subsequent eight-week detraining period. There was a main effect of time but
      no condition * time interaction or main effect of condition for muscle thickness
      and strength. Both muscle thickness and strength increased after the training
      period independent of the condition. This result suggests that PEBFR would not be
      an effective training method at least in an early phase of adaptation to high
      load resistance exercise.

PMID- 28448686
TI  - Plasma cytokines associated with febrile status epilepticus in children: A
      potential biomarker for acute hippocampal injury.
AB  - OBJECTIVE: Our aim was to explore the association between plasma cytokines and
      febrile status epilepticus (FSE) in children, as well as their potential as
      biomarkers of acute hippocampal injury. METHODS: Analysis was performed on
      residual samples of children with FSE (n = 33) as part of the Consequences of
      Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children
      with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of
      FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus
      proinflammatory cytokines in children with and without hippocampal T2
      hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE.
      RESULTS: Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were
      significantly elevated after FSE in comparison to controls. IL-1beta levels
      trended higher and IL-1RA trended lower following FSE, but did not reach
      statistical significance. Children with FSE were found to have significantly
      lower ratios of IL-1RA/IL-1beta and IL-1RA/IL-8. Specific levels of any one
      individual cytokine were not associated with FSE. However, lower ratios of IL
      1RA/IL-1beta, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6
      and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL
      8 were significantly lower in children with T2 hippocampal hyperintensity on MRI
      after FSE in comparison to those without hippocampal signal abnormalities.
      Neither individual cytokine levels nor ratios of IL-1RA/IL-1beta or IL-1RA/IL-8
      were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was
      strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393)
      of hippocampal T2 hyperintensity after FSE. SIGNIFICANCE: Our data support
      involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The
      identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute
      hippocampal injury following FSE is the most significant finding. If replicated
      in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker
      that offers rapid identification of patients at risk for ultimately developing
      mesial temporal lobe epilepsy (MTLE).

PMID- 28448689
TI  - Trends and factors associated with insomnia and sleep apnea in all United States
      military service members from 2005 to 2014.
AB  - Sleep disorders are a critical issue for the military, as they impact operational
      readiness, personnel health, wellbeing and health-care costs. The incidence of
      insomnia and obstructive sleep apnea (OSA) are increasing in the United States
      civilian population, and rates in military personnel exceed those of civilians.
      Using a comprehensive database, rates of medical encounters for insomnia and OSA
      were investigated and their associations with various demographic factors
      examined in the total US military population [1,381,406 +/- 25,123, mean +/-
      standard deviation (SD) personnel per year] from 2005 to 2014. Encounters for
      insomnia increased from 16 of 1000 in 2005 to 75 of 1000 in 2014 (372%).
      Encounters for OSA increased from 44 of 1000 in 2005 to 273 of 1000 in 2014
      (517%). Those experiencing the greatest increases in insomnia included women,
      individuals >=40 years of age, blacks, senior enlisted personnel and Army
      personnel compared to other military services. Those experiencing the greatest
      rates of OSA included men, individuals >=40 years of age, blacks, senior officers
      and Army personnel. Rates of insomnia and OSA increased linearly over time (R2  =
      0.95-0.99; P < 0.01) for every subpopulation except those aged <20 years. In
      response to this epidemic-like increase in sleep disorders, their prevention,
      identification and aggressive treatment should become a health-care priority of
      the US military.

PMID- 28448688
TI  - Efficacy and safety of evogliptin monotherapy in patients with type 2 diabetes
      and moderately elevated glycated haemoglobin levels after diet and exercise.
AB  - AIMS: To evaluate the efficacy and safety of evogliptin, a newly developed
      dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes (T2D)
      inadequately controlled by diet and exercise. MATERIALS AND METHODS: In this
      randomized, double-blind, placebo-controlled, parallel-group, multicentre, phase
      III study, 160 patients with T2D were assigned to either evogliptin 5 mg or
      placebo for 24 weeks. The primary endpoint was the mean change in glycated
      haemoglobin (HbA1c) from baseline to week 24. RESULTS: The mean baseline HbA1c
      levels were similar in the evogliptin and the placebo groups (7.20% +/- 0.56% vs
      7.20% +/- 0.63%, respectively). At week 24, evogliptin significantly reduced
      HbA1c levels from baseline compared with placebo (-0.23% vs 0.05%, respectively,
      P < .0001). Additionally, the proportion of patients achieving HbA1c <6.5% was
      significantly higher in the evogliptin group than in the placebo group (33.3% vs
      15.2%; P = .008). The overall incidence of adverse events, including
      hypoglycaemia, was similar in the 2 groups. CONCLUSIONS: In this 24-week study,
      once-daily evogliptin monotherapy significantly improved glycaemic control and
      was well tolerated in patients with T2D.

PMID- 28448690
TI  - Evaluation of column length and particle size effect on the untargeted profiling
      of a phytochemical mixture by using UHPLC coupled to high-resolution mass
      spectrometry.
AB  - Liquid chromatography coupled to high-resolution mass spectrometry is the
      technique of choice for the untargeted profiling of food matrices. Despite the
      high potential of high-resolution mass spectrometry, when dealing with complex
      mixtures, an efficient separation technique is also needed. The novel core-shell
      chromatographic columns packed with sub-2 MUm sized particles are claimed to show
      very good resolution. However, the analytes retention can be significantly
      altered when working under ultra-high performance chromatographic conditions. In
      this work, an evaluation of four chromatographic systems, with either a single or
      two in-series KinetexTM C18 columns, either packed with 2.6 or 1.7 MUm particles,
      is presented for the targeted analysis of a standard mixture and the untargeted
      analysis of a strawberry extract. An ultra-high performance chromatographic
      system coupled via an electrospray source to a hybrid quadrupole-Orbitrap mass
      spectrometer was used. From the extensive comparison, a surprising result was
      obtained, namely, that the system identifying the largest number of features was
      the one with two in-series connected columns with the larger particle size. The
      inconsistency among the theoretical assumptions and the applicative findings
      points out the importance of an extensive chromatographic evaluation for the
      comprehensive untargeted profiling of complex real samples.

PMID- 28448691
TI  - Clinical characterization and genetic analysis of Korean patients with X-linked
      Charcot-Marie-Tooth disease type 1.
AB  - Mutations in the gap junction protein beta 1 gene (GJB1) cause X-linked Charcot
      Marie-Tooth disease type 1 (CMTX1). CMTX1 is representative of the intermediate
      type of CMT, having both demyelinating and axonal neuropathic features. We
      analyzed the clinical and genetic characterization of 128 patients with CMTX1
      from 63 unrelated families. Genetic analysis revealed a total of 43 mutations
      including 6 novel mutations. Ten mutations were found from two or more unrelated
      families. p.V95M was most frequently observed. The frequency of CMTX1 was 9.6% of
      total Korean CMT family and was 14.8% when calculated within genetically
      identified cases. Among 67 male and 61 female patients, 22 females were
      asymptomatic. A high-arched foot, ataxia, and tremor were observed in 87%, 41%,
      and 35% of the patients, respectively. In the male patients, functional
      disability scale, CMT neuropathy score, and compound muscle action potential of
      the median/ulnar nerves were more severely affected than in the female patients.
      This study provides a comprehensive summary of the clinical features and spectrum
      of GJB1 gene mutations in Korean CMTX1 patients.

PMID- 28448692
TI  - A complex homozygous mutation in ABHD12 responsible for PHARC syndrome discovered
      with NGS and review of the literature.
AB  - PHARC syndrome (MIM612674) is an autosomal recessive neurodegenerative pathology
      that leads to demyelinating Polyneuropathy, Hearing loss, cerebellar Ataxia,
      Retinitis pigmentosa, and early-onset Cataracts (PHARC). These various symptoms
      can appear at different ages. PHARC syndrome is caused by mutations in ABHD12
      (alpha-beta hydrolase domain 12), of which several have been described. We report
      here a new complex homozygous mutation
      c.379_385delAACTACTinsGATTCCTTATATACCATTGTAGTCTTACTGCTTTTGGTGAACACA
      (p.Asn127Aspfs*23). This mutation was detected in a 36-year-old man, who
      presented neuropathic symptoms from the age of 15, using a next-generation
      sequencing panel. This result suggests that the involvement of ABHD12 in
      polyneuropathies is possibly underestimated. We then performed a comparative
      study of other patients presenting ABHD12 mutations and searched for genotype
      phenotype correlations and functional explanations in this heterogeneous
      population.

PMID- 28448693
TI  - Embedded ring injury - a rare presentation with an atypical aetiology.
AB  - A 45-year-old female patient presented to clinic with an almost completely
      embedded ring in the volar aspect of her right ring finger, with complete
      reepithelialisation over the superficial aspect of the ring. We present this
      unusual case of an embedded ring after an insect bite on the patient's ring
      finger. The patient had worn the ring for the previous 5 years without removing
      it and did not report any discomfort or traumatic injury. We discuss this case in
      the context of previously reported cases of an embedded ring, a rare presentation
      in itself, highlighting the key differences in both this patient's aetiology and
      the risk factors associated with the presentation.

PMID- 28448694
TI  - The joint effect of air pollution exposure and copy number variation on risk for
      autism.
AB  - Autism spectrum disorder is a complex trait with a high degree of heritability as
      well as documented susceptibility from environmental factors. In this study the
      contributions of copy number variation, exposure to air pollutants, and the
      interaction between the two on autism risk, were evaluated in the population
      based case-control Childhood Autism Risks from Genetics and Environment (CHARGE)
      Study. For the current investigation, we included only those CHARGE children (a)
      who met criteria for autism or typical development and (b) for whom our team had
      conducted both genetic evaluation of copy number burden and determination of
      environmental air pollution exposures based on mapping addresses from the
      pregnancy and early childhood. This sample consisted of 158 cases of children
      with autism and 147 controls with typical development. Multiple logistic
      regression models were fit with and without environmental variable-copy number
      burden interactions. We found no correlation between average air pollution
      exposure from conception to age 2 years and the child's CNV burden. We found a
      significant interaction in which a 1SD increase in duplication burden combined
      with a 1SD increase in ozone exposure was associated with an elevated autism risk
      (OR 3.4, P < 0.005) much greater than the increased risks associated with either
      genomic duplication (OR 1.85, 95% CI 1.25-2.73) or ozone (OR 1.20, 95% CI 0.93
      1.54) alone. Similar results were obtained when CNV and ozone were dichotomized
      to compare those in the top quartile relative to those having a smaller CNV
      burden and lower exposure to ozone, and when exposures were assessed separately
      for pregnancy, the first year of life, and the second year of life. No
      interactions were observed for other air pollutants, even those that demonstrated
      main effects; ozone tends to be negatively correlated with the other pollutants
      examined. While earlier work has demonstrated interactions between the presence
      of a pathogenic CNV and an environmental exposure [Webb et al., 2016], these
      findings appear to be the first indication that global copy number variation may
      increase susceptibility to certain environmental factors, and underscore the need
      to consider both genomics and environmental exposures as well as the mechanisms
      by which each may amplify the risks for autism associated with the other. Autism
      Res 2017, 10: 1470-1480. (c) 2017 International Society for Autism Research,
      Wiley Periodicals, Inc.

PMID- 28448695
TI  - Long-term memory in older children/adolescents and adults with autism spectrum
      disorder.
AB  - This study extends prior memory reports in autism spectrum disorders (ASD) by
      investigating memory for narratives after longer recall periods and by examining
      developmental aspects of narrative memory using a cross-sectional design. Forty
      seven older children/adolescents with ASD and 31 youth with typical development
      (TD) and 39 adults with ASD and 45 TD adults were compared on memory for stories
      from standardized measures appropriate for each age group at three intervals
      (immediate, 30 min, and 2 day). Both the youth with and without ASD had
      difficulty with memory for story details with increasing time intervals. More of
      the youths with ASD performed in the range of impairment when recalling the
      stories 2 days later as compared to the TD group. The adults with ASD had more
      difficulty on memory for story details with increasing delay and were poorer at
      recall of thematic information (needed to create a gist) across the three delay
      conditions as compared to the TD group. Analyses of the individual results
      suggested that memory for details of most of the adults with ASD was not impaired
      when applying a clinical standard; however, a significant percentage of the
      adults with ASD did not make use of thematic information to organize the
      narrative information, which would have helped them to remember the stories. The
      youth with and without ASD performed similarly when both were at a stage of
      development when memory for details is the primary strategy. The adults with ASD
      had difficulty with use organizational strategies to support episodic memory.
      Autism Res 2017, 10: 1523-1532. (c) 2017 International Society for Autism
      Research, Wiley Periodicals, Inc.

PMID- 28448696
TI  - New Zealand Rheumatology Association and Australian Rheumatology Association with
      the Rheumatology Health Professionals Association Joint Annual Scientific
      Meeting, 20-23 May 2017, Auckland Convention Centre, Auckland, New Zealand.

PMID- 28448697
TI  - National Trends in Antidepressant, Benzodiazepine, and Other Sedative-Hypnotic
      Treatment of Older Adults in Psychiatric and Primary Care.
AB  - OBJECTIVE: To describe how use of antidepressants, benzodiazepines, and other
      anxiolytic/sedative-hypnotics among older adults (age >= 65 years) has changed
      over time among visits to primary care providers and psychiatrists. METHODS: Data
      were from the National Ambulatory Medical Care Survey (years 2003-2005 and 2010
      2012), a nationally representative cross-section of outpatient physician visits.
      Analysis focused on visits to primary care providers (n = 14,282) and
      psychiatrists (n = 1,095) at which an antidepressant, benzodiazepine, or other
      anxiolytic/sedative-hypnotic was prescribed, which were stratified by demographic
      and clinical characteristic (including ICD-9-CM diagnosis) and compared across
      study intervals. Odds of medication use were calculated for each stratum,
      adjusting for demographic and clinical characteristics. RESULTS: The visit rate
      by older adults to primary care providers where any of the medications were
      prescribed rose from 16.4% to 21.8% (adjusted odds ratio [AOR] = 1.43, P < .001)
      while remaining steady among psychiatrists (75.4% vs 68.5%; AOR = 0.69, P = .11).
      Primary care visits rose for antidepressants (9.9% to 12.3%; AOR = 1.28, P = .01)
      and other anxiolytic/sedative-hypnotics (3.4% to 4.7%; AOR = 1.39, P = .01), but
      the largest growth was among benzodiazepines (5.6% to 8.7%; AOR = 1.62, P <
      .001). Among patients in primary care, increases primarily occurred among men,
      non-Hispanic white patients, and those with pain diagnoses as well as those with
      no mental health or pain diagnoses. CONCLUSIONS: From 2003 to 2012, use of the
      most common psychotropic medications among older adults seen in primary care
      increased, with concentration among patients with no mental health or pain
      diagnosis. As the population of older adults grows and receives mental health
      treatment in primary care, it is critical to examine the appropriateness of
      psychotropic use.

PMID- 28448698
TI  - Characteristics and Risk Factors for Suicide and Deaths Among College Students: A
      23-Year Serial Prevalence Study of Data From 8.2 Million Japanese College
      Students.
AB  - OBJECTIVE: Suicide is a leading cause of death for college students. The aim of
      this study was to identify risk factors of suicide among college students that
      could improve university services to help prevent college suicide. METHODS: We
      conducted a 23-year serial prevalence study of the prevalence and characteristics
      of death and suicide among 8,262,314 Japanese college students. We analyzed rates
      of suicide from the 1989 to 1990 academic year through the 2011-2012 academic
      year and characterized suicide among this population, focusing on students' sex
      and psychiatric and academic backgrounds to identify risk factors for suicide.
      RESULTS: Suicide rates increased throughout the 23 years, and suicide was the
      leading cause of death every year from 1996 onward. Suicide accounted for 42.4%
      of all deaths that happened in the 23 years. Male students, medicine majors,
      students in the final year of their program, and students who completed extra
      years of schooling or took academic leaves of absence were at higher risk for
      suicide. Only 16.4% had received an official psychiatric diagnosis and 16.0% had
      received services through the university health center prior to the suicides.
      CONCLUSIONS: Results suggest the need for a stronger support system for college
      students. Areas for improvement could include better advertising of mental health
      services, student and staff education about suicide risk factors, and mentorship
      and outreach programs for students in their final year of classes, those majoring
      in medicine, and those who have taken leaves of absence or failed classes.
      Accommodations at the administrative level would also be helpful for students who
      need to retake classes or transfer credit.

PMID- 28448699
TI  - Challenges in Testing Intranasal Ketamine in Obsessive-Compulsive Disorder.

PMID- 28448700
TI  - Duration and Relevance of Untreated Psychiatric Disorders, 2: Nonpsychotic
      Psychiatric Disorders and Substance Use Disorders.

PMID- 28448701
TI  - Valproate Intoxication in a Patient With Blood Valproate Levels Within
      Therapeutic Range.

PMID- 28448702
TI  - Ketamine for Depression, 1: Clinical Summary of Issues Related to Efficacy,
      Adverse Effects, and Mechanism of Action.
AB  - Ketamine is an anesthetic drug that is also used for off-label indications such
      as the mediation of analgesia and sedation in various settings. It is
      additionally recognized as an agent with antidepressant potential. For
      depression, it is most commonly administered as a slow intravenous infusion in
      subanesthetic doses (usually 0.5 mg/kg). As an antidepressant, is strikingly
      different from conventional antidepressant drugs in that it brings about rapid
      and marked attenuation of depressive symptoms even in patients with refractory
      depression. The benefits are observed within hours of administration, peak after
      about a day, and are lost 3-12 days later. Patients who do not benefit after the
      initial dose may benefit with serial dosing or at higher doses. Benefits can be
      maintained for weeks to months by the continuation of ketamine sessions at 2- to
      4-day intervals. Adverse effects include dissociative and psychotomimetic changes
      that are almost always mild and transient, if present; transient elevation of
      heart rate and blood pressure often occur. These changes are usually well
      tolerated and are very seldom responsible for treatment discontinuation. Whereas
      ketamine is an N-methyl-d-aspartate receptor antagonist, and whereas much is
      known about its different biological effects, its actions that mediate the
      antidepressant response are presently not known for certain. Although big data on
      ketamine are presently unavailable, the drug holds promise in the treatment of
      depression, especially refractory depression.

PMID- 28448703
TI  - [Teachers Training Diplomate in Health Area].
AB  - No Abstract available.

PMID- 28448704
TI  - [Retrograde intramedullary nail fixation for Charcot neuroarthropathy].
AB  - : Charcot arthropathy is defined as an articular degenerative, chronic,
      progressive disease that affects one or more peripheral joints, develops as a
      result of a failure in the normal sensory perception (pain and proprioception) in
      the innervation of joints located in the foot and ankle, is characterized by
      destructive bone lesions without the presence of infection. Neuropathy is
      directly associated with diabetes mellitus type 1 and 2. Surgery is indicated
      when there is severe involvement of soft tissue, foot joints are unstable, at the
      presence of chronic or recurrent ulcers or when the foot and ankle can not fit to
      a normal shoe, and had limitation to perform activities of daily living. MATERIAL
      AND METHODS: Charcot arthropathy is defined as an articular degenerative,
      chronic, progressive disease that affects one or more peripheral joints, develops
      as a result of a failure in the normal sensory perception (pain and
      proprioception) in the innervation of joints located in the foot and ankle, is
      characterized by destructive bone lesions without the presence of infection.
      Neuropathy is directly associated with diabetes mellitus type 1 and 2. Surgery is
      indicated when there is severe involvement of soft tissue, foot joints are
      unstable, at the presence of chronic or recurrent ulcers or when the foot and
      ankle can not fit to a normal shoe, and had limitation to perform activities of
      daily living. DESIGN: observational, prospective, transversal, descriptive.
      SAMPLE: patients diagnosed with Charcot neuropathy type 3a of Brodsky. Surgically
      treated by ankle arthrodesis with an intramedullary blocked nail, from January
      2010 to August 2015. RESULTS: 16 patients were analyzed. Preoperative AOFAS score
      was 35.0 +/- 5.2 points. Postoperative follow-up period of 4 years to 7 months.
      Postoperative AOFAS scale showed an improvement of 40 points (p = 0.0001).
      CONCLUSIONS: The proposed treatment allows bone stabilization, resulting in a
      full foot plantar support and decreases the occurrence of chronic ulcers that are
      difficult to treat, and is an alternative method that avoids lead to amputation.

PMID- 28448705
TI  - [Results of the Salters osteotomy as a definitive treatment for the developmental
      dysplasia of the hip].
AB  - OBJECTIVE: Evaluate the results of open reduction associated to a Salter
      osteotomy at nine months of age for treatment of the developmental Dysplasia of
      the Hip. MATERIAL AND METHODS: Case- series of unilateral Developmental Dysplasia
      of the hip treated between July 2004- December 2008 with follow-up at 3, 6 and 9
      months postop. RESULTS: 16 patients, 13 females (81%) 3 males (19%). we did an
      open reduction and Salters osteotomy at 9 months on average (8- 10 months); the
      most effected side were the left hip on 75%. at 9 months of follow up 15 patients
      had a McKay score excellent and 1 good. Only one patient was followed up at one
      year with no pain, full range of motion and stable. CONCLUSION: open reduction
      and salter osteotomy without preoperative traction is an effective treatment in
      the short-term; the range of motion could be affected. It is important that the
      spica cast were applied in a staged manner and in secured position.

PMID- 28448706
TI  - [Prognostic factors for post surgical complications in bone infection and
      pseudarthrosis].
AB  - Bone infection and nonunion are the main orthopedic and traumatic complications
      whose treatment remains a challenge because multiple factors are involved in the
      rate of failures when you try to correct them. Knowing these factors were the
      problem that caused the research through a prospective longitudinal study of 83
      patients of 43.3 +/- 16.1 years old. They were treated for aseptic and septic
      nonunion, osteomyelitis, osteitis, malunion or infected joint replacement. The
      cases were classified with or without postoperative complications and outcome
      related to systemic and local factors taken prognostic model Cierny-Mader as
      factors affecting immune surveillance, metabolism and local vascularization. For
      bivariate analysis of data Chi2 it was applied or where appropriate Fishers exact
      test; for multivariate analysis model not conditional binary logistic regression
      method was applied Wald backward to select the significant prognostic factors.
      The alpha error was set 0.05. General complications occurred in 51.8% of cases.
      Local factors (lymphedema, arteritis, venous insufficiency, loss of skin) with an
      OR of 5.0 (95% CI 1.0-24.9, p = 0.03), septic nonunion with OR of 5.0 (95% CI 1.9
      13.0, p = 0.001) and segmental fractures with an OR of 3.2 (95% CI 0.8-13.0, p =
      0.07) were the prognostic factors identified in the bivariate analysis; however,
      the logistic regression only selected as the septic pseudoarthrosis as a
      significant factor. It is necessary to detect and if necessary control or
      eliminate those factors that can directly affect poor postoperative results.

PMID- 28448707
TI  - [Joint replacement and giant-cell tumor. Report of 8 cases].
AB  - INTRODUCTION: The giant-cell tumor is an aggressive neoplasia, represents
      approximately from the 5 the 8.6% of primary bone tumors; more of 50% affects the
      pelvic extremity, being able to affect the totality of the bones. OBJECTIVE: To
      present the case series of tumors around the knee and hip that we offered a
      tumoral joint replacement as an alternative to amputation. MATERIAL AND METHODS:
      We present eight cases of extensive giant cells tumors, we did en bloc resection
      and tumoral joint replacement. RESULTS: The clinical and radiological evolution
      was satisfactory, without postoperative complications and the most important,
      avoided an amputation with a better quality of life. DISCUSSION: Alternative
      reconstructive treatment option with a recovery to its normal life in a 80% and a
      low index of complications.

PMID- 28448708
TI  - [Wrist X ray for analysis of the articular surface of distal radius].
AB  - : In the distal radius fracture requires radiographic views that allow you to see
      the articular surface without interposition. The objective was to determine
      whether lateral radiographic projections 7 and 22 degrees  improve the analysis
      of this surface. METHOD: Case series study with radiographs of healthy and
      operated patients, in order to identify the lunate and scaphoid facets in lateral
      and anteroposterior projections. Qualitative analysis was made on the radiographs
      of the distal radius with wedges of 7 and 22 degrees  in the lateral views and 11
      degrees  in the anteroposterior view. RESULTS: There were evaluated 14
      radiographs of the distal radius of healthy volunteers and 10 patients with
      distal radius fractures who recieved surgery with internal fixation, and also two
      anatomical models. In 14 healthy and 10 patients, it was found that the views at
      7 and 22 degrees  can be better appreciated radio lunate and radio scaphoid
      surface respectively, observing images with less overlapping in the radiograph of
      22 degrees  in both groups. DISCUSSION: Radiographic views are important to
      determine the immediate results of fixation on a distal radius fracture. We
      observe that the lateral view at 7 degrees  is better to show the screws on the
      lunate facet of the radius. The lateral view at 22 degrees  is better to show the
      facet of the radius with the scaphoid. Finally, the anteroposterior projection at
      11 degrees  allows us to see the radio carpal joint with lower image overlay.

PMID- 28448709
TI  - [Ankle arthroscopy in treatment of Bosworth fracture].
AB  - The Bosworth fracture is a pattern of fracture-dislocation of the ankle joint
      with fixed dislocation of the proximal part of the fibula behind the posterior
      malleolus. It is a rare injury, which requires high index of suspicion for
      diagnosis. Fixed dislocation of the fibula does not allow for closed reduction,
      so open reduction and fixation of fibula or tibia is required. We present a case
      report of a patient who suffered a Bosworth fracture, with associated medial
      malleolus fracture. She underwent surgical treatment with open reduction and
      internal fixation of the fibula and tibia. We also performed anterior arthroscopy
      of the ankle, to evaluate the tibiofibular syndesmosis, remove loose
      osteochondral fragments, and perform debridement and microfracture of unstable
      chondral lesions of the talus. One year after injury, she remains with occasional
      pain and a normal range of motion comparing to the contralateral ankle joint.
      Bosworth fracture is a serious and rare injury, which requires early diagnosis
      and urgent surgical treatment. Performing ankle arthroscopy in the acute
      treatment of the Bosworth fracture allows for diagnosis and treatment of
      associated intra-articular injuries, as well as assisting with adequate fracture
      reduction and evaluation of the tibiofibular syndesmosis stability.

PMID- 28448710
TI  - [Toddler's fracture, case report and review of literature].
AB  - INTRODUCTION: The suspected diagnosis of a Toddler's fracture can often be
      complicated by an unclear history, the lack of specific clinical findings and the
      absence of obvious changes in the initial radiographs. We present the case of an
      infant of 3 years and 7 months old with a history of falling from her own height
      with a rotation mechanism of the left pelvic limb. The purpose of this paper is
      to describe the etiopathology, diagnosis and therapeutic management of these
      fractures. DISCUSSION: The clinical history, physical examination and the use of
      imaging studies help identify Toddler's fractures, pathology that must be known
      to medical specialists for an ideal treatment.

PMID- 28448711
TI  - [Cemented polyethylene insert in a well fixed Total knee replacement. Case
      report].
AB  - We present the case of a 94 years- old patient, which was operated 14 years ago
      of a right total knee replacement for osteoarthritis, actually she suffers of
      pain and instability; her X ray shown polyethylene wear without loosening of the
      metal components. The polyethylene insert is not manufactured anymore so we
      decided cement a new polyethylene insert on the native tibial baseplate. The two
      years follow up show us a patient asymptomatic, good function and no
      radiolucencies on the tibial component. We only found a similar case report in
      Madrid and we believed that this decision, taken from total hip revisions, will
      succeed.

PMID- 28448712
TI  - [Quadratus femoris muscle tear].
AB  - BACKGROUND: Quadratus femoris tear is an uncommon injury that usually cause hip
      pain, it incidence is unknown. The patient can suffer of posterior gluteal pain
      or groin pain or both, which makes accurate diagnosis difficult, because the
      differential diagnosis of hip pain is broad. CLINICAL CASE: A 65 years old male,
      with gluteal and groin pain presented during tennis; evaluated by neurologist
      with lumbosacral magnetic resonance imaging (MRI) (normal) and referred to
      physical therapy, a pelvic MRI was required, finding an unsuspected quadratus
      femoris tear. CONCLUSION: MRI with its superior soft-tissue resolution and
      multiplanar capability is an excellent adjunct to physical examination because it
      shows the anatomic location of the abnormality, aiding the clinician to make
      unsuspected diagnoses.

PMID- 28448713
TI  - [Ligamentun teres of the hip. Bibliographic revision].
AB  - The role and function of the ligamentum teres has drawn our attention in the last
      years due to the increasing and performance in hip arthroscopy, few is written in
      the literature, this is why we proposed to perform and assessed a review on the
      current literature of the anatomy, function, diagnose and rupture of the
      ligamentum teres of the hip.

PMID- 28448714
TI  - Octopus-Inspired Assembly of Nanosucker Arrays for Dry/Wet Adhesion.
AB  - The octopus is capable of adhering to slippery, rough, and irregular surfaces in
      the marine intertidal zone because of its periodic infundibulum-shaped suckers on
      the arms. Here, we present a scalable self-assembly technology for fabricating
      adhesion materials that mimic octopus sucker functionality. By utilizing spin
      coated two-dimensional colloidal crystals as templates, non-close-packed
      nanosucker arrays are patterned on silicone substrates. The resulting nanosuckers
      can be deformed to exhibit great adhesive capacities on both microrough and flat
      surfaces in dry and wet environments. This indicates a probable biomimetic
      solution to the challenge of wound care.

PMID- 28448715
TI  - Acyl Carrier Protein Cyanylation Delivers a Ketoacyl Synthase-Carrier Protein
      Cross-Link.
AB  - Acyl carrier proteins (ACPs) are central hubs in polyketide and fatty acid
      biosynthetic pathways, but the fast motions of the ACP's phosphopantetheine
      (Ppant) arm make its conformational dynamics difficult to capture using
      traditional spectroscopic approaches. Here we report that converting the terminal
      thiol of Escherichia coli ACP's Ppant arm into a thiocyanate activates this site
      to form a selective cross-link with the active site cysteine of its partner
      ketoacyl synthase (FabF). The reaction releases a cyanide anion, which can be
      detected by infrared spectroscopy. This represents a practical and generalizable
      method for obtaining and visualizing ACP-protein complexes relevant to
      biocatalysis and will be valuable in future structural and engineering studies.

PMID- 28448716
TI  - Phosphorylation Weakens but Does Not Inhibit Membrane Binding and Clustering of K
      Ras4B.
AB  - K-Ras4B is one of the most frequently mutated Ras isoforms in cancer. The
      signaling activity of K-Ras4B depends on its localization to the plasma membrane
      (PM), which is mainly mediated by its polybasic farnesylated C-terminus. On top
      of the constitutive cycles that maintain the PM enrichment of K-Ras4B,
      conditional phosphorylation at Ser181 located within this motif has been found to
      be involved in regulating K-Ras4B's cell distribution and signaling activity.
      However, discordant observations have undermined our understanding of the role
      this phosphorylation plays. Here, we report an efficient strategy for producing K
      Ras4B simultaneously bearing phosphate, farnesyl, and methyl modifications on a
      preparative scale, a very useful in vitro system when used in concert with model
      biomembranes. By using this system, we determined that phosphorylation at Ser181
      does not fully inhibit membrane binding and clustering of K-Ras4B but reduces its
      membrane binding affinity, depending on membrane fluidity. In addition,
      phosphorylated K-Ras4B maintains tight association with its cytosolic shuttle
      protein PDEdelta. After delivering K-Ras4B containing nonhydrolyzable
      phosphoserine mimetic into cells, the protein displayed a decreasing PM
      distribution compared with nonphosphorylable K-Ras4B, implying that
      phosphorylation might facilitate the dissociation of K-Ras4B from the PM. In
      addition, phosphorylation does not alter the localization of K-Ras4B in the
      liquid-disordered lipid subdomains of the membrane but slightly alters the
      thermotropic properties of K-Ras4B-incorporated membranes probably due to minor
      differences in membrane partitioning and dynamics. These results provide novel
      mechanistic insights into the role that phosphorylation at Ser181 plays in
      regulating K-Ras4B's distribution and activity.

PMID- 28448717
TI  - Insight on Structure of Water and Ice Next to Graphene Using Surface-Sensitive
      Spectroscopy.
AB  - The water/graphene interface has received considerable attention in the past
      decade due to its relevance in various potential applications including energy
      storage, sensing, desalination, and catalysis. Most of our knowledge about the
      interfacial water structure next to graphene stems from simulations, which use
      experimentally measured water contact angles (WCAs) on graphene (or graphite) to
      estimate the water-graphene interaction strength. However, the existence of a
      wide spectrum of reported WCAs on supported graphene and graphitic surfaces makes
      it difficult to interpret the water-graphene interactions. Here, we have used
      surface-sensitive infrared-visible sum frequency generation (SFG) spectroscopy to
      probe the interfacial water structure next to graphene supported on a sapphire
      substrate. In addition, the ice nucleation properties of graphene have been
      explored by performing in situ freezing experiments as graphitic surfaces are
      considered good ice nucleators. For graphene supported on sapphire, we observed a
      strong SFG peak associated with highly coordinated, ordered water next to
      graphene. Similar ordering was not detected next to bare sapphire, implying that
      the observed ordering of water molecules in the former case is a consequence of
      the presence of graphene. Our analysis indicates that graphene behaves like a
      hydrophobic (or negatively charged) surface, leading to enhanced ordering of
      water molecules. Although liquid water orders next to graphene, the ice formed is
      proton disordered. This research sheds light on water-graphene interactions
      relevant in optimizing the performance of graphene in various applications.

PMID- 28448718
TI  - Cannabis use by women during pregnancy does not influence infant DNA methylation
      of the dopamine receptor DRD4.
AB  - BACKGROUND: Maternal cannabis use in pregnancy is linked with long-term adverse
      behavioral outcomes in offspring. Epigenetic processes established in utero that
      affect dopaminergic (reward) signaling may mediate risks. Associations between
      cannabis use and offspring DNA methylation have not been investigated; however,
      maternal tobacco smoking in pregnancy is associated with distinct patterns of DNA
      methylation at birth and beyond. OBJECTIVES: To determine whether maternal
      cannabis use is associated with methylation of the dopamine receptor gene DRD4
      promoter in infants. METHODS: Mothers in the Triple B study provided detailed
      information on drug use in each trimester of pregnancy. Buccal swabs were
      collected from neonates at 8 weeks (n = 804, 51.7% male, and 48.3% female). DRD4
      promoter DNA methylation was measured using SEQUENOM MassARRAY. RESULTS: Fifty
      seven of the women in the study reported drug use during pregnancy, of whom 44
      used cannabis. Of 19 cytosine-phosphate-guanine dinucleotides (CpG) units tested
      in DRD4, gestational cannabis use was associated with offspring methylation at 1
      CpG unit in multivariate models (beta + 1.48, CI: 0.02 to 2.93, and p = 0.047).
      At another site there was weak evidence that both cannabis and other drug use
      were independently associated with increased methylation, while the association
      with tobacco was in the reverse direction (cannabis use beta + 0.67, CI: -0.12 to
      1.46, and p = 0.09; other drug use beta + 1.11, CI: 0.17 to 2.05, and p = 0.02;
      tobacco use beta -0.41, CI: -0.85 to 0.03, and p = 0.07). None of the
      associations would remain significant after correction for multiple testing.
      CONCLUSION: There is no strong evidence that maternal cannabis use in pregnancy
      is associated with offspring DRD4 methylation.

PMID- 28448719
TI  - Use of native aquatic macrophytes in the reduction of organic matter from dairy
      effluents.
AB  - Considering the diversity and the unexplored potential of regional aquatic flora,
      this study aimed to identify and analyze the potential of native aquatic
      macrophytes to reduce the organic matter of dairy wastewater (DW) using
      experimental constructed wetlands. The dairy wastewater (DW) had an average
      chemical oxygen demand (COD) of 7414.63 mg/L and then was diluted to 3133.16 mg/L
      (D1) and to 2506.53 mg/L (D2). Total solids, COD, temperature, and pH analyses
      were performed, and the biochemical oxygen demand (BOD) was estimated from the
      COD values. The best performance in the reduction of the organic matter was
      observed for Polygonum sp. (87.5% COD and 79.6% BOD) and Eichhornia paniculata
      (90% COD and 83.7% BOD) at dilution D1, on the 8th day of the experiment.
      However, the highest total solids removal was observed for Polygonum sp. (32.2%),
      on the 4th day, at dilution D2. The total solid (TS) concentration has also
      increased starting from the 8th day of the experiment was observed which may have
      been due to the development of mosquito larvae and their mechanical removal by
      sieving, thus changing the steady state of the experimental systems. The
      macrophytes Polygonum sp. and E. paniculata were considered suitable for the
      reduction of organic matter of DW using constructed wetlands.

PMID- 28448720
TI  - Mosaic Neurofibromatosis Type 1 in Children: A Single-Institution Experience.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder caused by
      loss-of-function mutation in the NF1 gene. Segmental or mosaic NF1 (MNF) is an
      uncommon presentation of the NF1 result of postzygotic mutations that present
      with subtle localised clinical findings. OBJECTIVES: Our study's objectives were
      to describe the clinical characteristics of children with MNF. METHODS: We
      conducted a cross-sectional study of children diagnosed with MNF at the Hospital
      for Sick Children in Toronto, Canada, from January 1992 to September 2012. Data
      were abstracted from health records and analysed using a standardised data
      collection form approved by our hospital Research Ethics Board. RESULTS: We
      identified 60 patients with MNF; 32 of 60 (53.3%) were female. Mean +/- SD age at
      first assessment was 10.6 +/- 4.6 years. The most common initial physical
      manifestation in 39 of 60 (65.0%) patients was localised pigmentary changes only,
      followed by plexiform neurofibromas only in 10 of 60 (16.7%) and neurofibromas
      only in 9 of 60 (15.0%). Unilateral findings were seen in 46 of 60 (76.7%)
      patients. Most common associations identified included learning disabilities
      (7/60; 12%) and bony abnormalities (6/60; 10.0%). CONCLUSIONS: MNF is an
      underrecognised condition with potential implications for patients. Children
      mostly present with pigmentary anomalies only. Most patients do not develop
      associated findings or complications before adulthood, but long-term follow-up
      will help determine outcomes and possible associations. Recognition and
      confirmation of the diagnosis is important to provide follow-up and genetic
      counselling to patients.

PMID- 28448721
TI  - Triplicate Sputum Cultures for Efficacy Evaluation of Novel Antituberculosis
      Regimens.

PMID- 28448722
TI  - Immunostaining of Immunoglobulin G4 in the Lacrimal Sac.
AB  - PURPOSE: To immunohistochemically examine the lacrimal sac walls harvested during
      dacryocystorhinostomy using an immunostain for immunoglobulin G4 (IgG4). METHODS:
      Forty-four lacrimal sac walls were evaluated. We determined "intensively
      positive," "sparsely positive," or "negative" staining when the specimens showed
      IgG4-positive lymphoplasmacytic staining with or without >50 IgG4-positive
      cells/high-power field, or the absence of stained IgG4-positive cells. RESULTS:
      Intensively positive, sparsely positive, or negative staining was observed in 8
      (18.2%), 14 (31.8%), and 22 specimens (50.0%), respectively. Stained cells
      infiltrated the subepithelial layer in all specimens with positive staining. Four
      of the 8 specimens demonstrated partial epithelial denudation with loss of goblet
      cells. CONCLUSIONS: IgG4-positive lymphoplasmacytic infiltration was observed in
      the subepithelial layer in specimens with intensively positive staining, of which
      some showed a partially denuded epithelium with loss of goblet cells. These may
      lead to narrowing of the lacrimal sac lumen and adhesions of the sac walls.

PMID- 28448723
TI  - Pediatric Uveitis in a Well-Defined Population: Improved Outcomes with
      Immunosuppressive Therapy.
AB  - PURPOSE: The aim of this study is to assess the incidence, etiology, visual
      outcomes, and complication rates of pediatric uveitis patients at a dedicated
      multidisciplinary uveitis clinic in Northern Ireland. METHODS: Data were
      collected from charts of all patients attending the clinic at the Belfast Health
      and Social Care Trust between 2011 and 2015. Demographics, disease
      characteristics, treatments, visual acuity, and complications were recorded.
      RESULTS: There were 94 patients with uveitis onset before the age of 16 years.
      Etiology was mixed with JIAU the leading cause accounting for 48% of patients.
      Thirty-seven percent of patients had known complications at presentation and 65%
      by final visit. Systemic treatments were used in 65% of cases. Ninety-two percent
      of eyes had a final visual acuity >= 6/12 at a mean follow-up of 5 years.
      CONCLUSIONS: The etiology of uveitis in this pediatric population is mixed. With
      close monitoring, most patients maintain good vision.

PMID- 28448724
TI  - In response to: "Ranjan, P, Joshi P, and Gupta M. Staphylococcus aureus induced
      endogenous endophthalmitis with pink hypopyon."

PMID- 28448725
TI  - Endogenous Cryptococcal Endophthalmitis in Immunocompetent Host: Case Report and
      Review of Multimodal Imaging Findings and Treatment.
AB  - PURPOSE: To describe a case of bilateral endogenous cryptococcal endophthalmitis
      in an immunocompetent host and to review adjunctive ophthalmic imaging patterns
      and treatment. METHODS: A retrospective case report. RESULTS: A 45-year-old
      female patient with two distinct presentations of endogenous cryptococcal
      endophthalmitis in each eye presented initially with progressive blurred vision
      in the left eye, beginning more than 10 years after a craniotomy with
      ventriculoperitoneal shunt. Complete ophthalmic imaging was conducted and
      compared with data from previous literature. Administration of amphotericin-B had
      poorly responded; however, consolidation of fluconazole resulted in disease
      stabilization. CONCLUSIONS: Bilateral intraocular cryptococcal infection can
      present with two distinct patterns of posterior segment findings. A review of
      ophthalmic imaging patterns found consistency in some characteristics of A-scan
      ultrasonogram and fundus fluorescein angiogram. Besides conventional treatment,
      voriconazole is likely to play an important role in the management of
      cryptococcal endophthalmitis.

PMID- 28448726
TI  - Intravitreal Injection of Sulfamethoxazole and Trimethoprim Associated with
      Dexamethasone as an Alternative Therapy for Ocular Toxoplasmosis.
AB  - PURPOSE: To evaluate intravitreal injections of sulfamethoxazole/trimethoprim in
      association with dexamethasone for treating toxoplasmic retinochoroiditis.
      METHODS: Thirteen patients with active, recurrent ocular focal toxoplasmic
      retinochoroiditis and visual acuity worse than 20/63 in the affected eye were
      included. Ocular toxoplasmosis was diagnosed according to the classic clinical
      findings. The primary end point was the change in the final best-corrected visual
      acuity (BCVA). RESULTS: The intraocular inflammation decreased within 2 weeks
      after injection in all eyes and resolved in 8 (62%) eyes with only one injection
      after 30 days; the remaining eyes received two injections. In all eyes, the
      retinitis was inactive and no patient had decreased early treatment diabetic
      retinopathy study lines of BCVA at the final examination. CONCLUSION: The
      combination of intravitreal trimethoprim/sulfamethoxazole and dexamethasone might
      be an alternative treatment strategy in patients with toxoplasmic
      retinochoroiditis.

PMID- 28448727
TI  - Long-Term Outcomes of a Large Cohort of Patients with Eales' Disease.
AB  - PURPOSE: To analyze the long-term visual outcomes of Eales' patients. METHODS: A
      retrospective review of Eales' patients diagnosed between 1985 and 1995 with >10
      years follow-up done. RESULTS: We included 500 patients (898 eyes) with mean
      follow-up duration of 15.8 years (10-25 years), and 81% patients had bilateral
      disease. Patients using oral steroid during acute stage disease had significantly
      better visual outcome at the final visit [0.42 logMar(6/18) +/- 0.723
      logMar(6/30)] compared to patients who did not receive oral steroids [(0.5907
      logMar(6/24) +/- 0.945 logMar(6/48)] (p = 0.004). Patients who received laser
      therapy had significantly better visual outcome at the final visit [(0.415
      logMar(6/18) +/- 0.66 logMar(6/30)] compared to those who did not undergo laser
      treatment [(0.9237 logMar(6/48) +/- 1.31 logMar(6/120)] (p < 0.001). Poor
      presenting visual acuity and late stage of presentation were associated with poor
      visual outcome. Fifty-two percent of eyes had <5 recurrences over 10 years.
      CONCLUSION: Eales' disease is a bilateral recurrent retinal vasculitis disorder
      and timely treatment with steroid and/or laser photocoagulation result in better
      visual outcomes.

PMID- 28448728
TI  - Does an Injection of Adipose-Derived Mesenchymal Stem Cells Loaded in Fibrin Glue
      Influence Rotator Cuff Repair Outcomes? A Clinical and Magnetic Resonance Imaging
      Study.
AB  - BACKGROUND: The mesenchymal stem cell (MSC)-based tissue engineering approach has
      been developed to improve the treatment of rotator cuff tears.
      Hypothesis/Purpose: The purpose was to determine the effect of an injection of
      adipose-derived MSCs loaded in fibrin glue during arthroscopic rotator cuff
      repair on clinical outcomes and to evaluate its effect on structural integrity
      using magnetic resonance imaging (MRI). The hypothesis was that the application
      of adipose-derived MSCs would improve outcomes after the surgical repair of a
      rotator cuff tear. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS:
      Among 182 patients treated with arthroscopic surgery for a rotator cuff tear, 35
      patients treated with arthroscopic rotator cuff repair alone (conventional group)
      were matched with 35 patients who underwent arthroscopic rotator cuff repair with
      an injection of adipose-derived MSCs loaded in fibrin glue (injection group)
      based on sex, age, and lesion size. Outcomes were assessed with respect to the
      visual analog scale (VAS) for pain, range of motion (ROM) (including forward
      flexion, external rotation at the side, and internal rotation at the back), and
      functional measures of the Constant score and University of California, Los
      Angeles (UCLA) shoulder rating scale. Repaired tendon structural integrity was
      assessed by using MRI at a minimum of 12 months after surgery, and the mean
      clinical follow-up was 28.8 +/- 4.2 months in the conventional group and 28.3 +/-
      3.8 months in the injection group. RESULTS: The mean VAS score at rest and during
      motion improved significantly in both groups after surgery. However, there were
      no significant differences between the groups at the final follow-up ( P = .256
      and .776, respectively). Compared with preoperative measurements, forward flexion
      and external rotation at the side significantly improved at the final follow-up
      in both groups (all P < .05). However, no significant improvements in internal
      rotation at the back were observed in either group ( P = .625 and .834 for the
      conventional and injection groups, respectively). There were also no significant
      differences between the groups at the final follow-up for any of the 3 ROM
      positions (all P > .05). The mean Constant score and UCLA score improved
      significantly in both groups after surgery, but there were no significant
      differences between the groups at the final follow-up ( P = .634 and .302,
      respectively). MRI indicated a retear rate of 28.5% in the conventional group and
      14.3% in the injection group ( P < .001). CONCLUSION: This study revealed that an
      injection of adipose-derived MSCs loaded in fibrin glue during rotator cuff
      repair could significantly improve structural outcomes in terms of the retear
      rate. There were, however, no clinical differences in the 28-month period of
      follow-up. Although still in the early stages of application, MSC augmentation of
      surgical rotator cuff repair appears useful for providing an adequate biological
      environment around the repair site.

PMID- 28448729
TI  - Proteomics of blood plasma/serum samples stored in biobanks: insights for
      clinical application.

PMID- 28448730
TI  - Retinal Manifestations of Juvenile Dermatomyositis: Case Report of Bilateral
      Diffuse Chorioretinopathy with Paracentral Acute Middle Maculopathy and Review of
      the Literature.
AB  - PURPOSE: To review a case of bilateral diffuse chorioretinopathy as a presenting
      sign of juvenile dermatomyositis (JDM) and review the literature regarding
      retinal manifestations associated with this disease. METHODS: Review of case
      record and literature regarding retinal manifestations related to juvenile
      dermatomyositis. RESULTS: A 13-year-old girl presented with bilateral diffuse
      chorioretinopathy as the presenting sign of juvenile dermatomyositis. A review of
      the literature suggests that retinopathy associated with JDM is a rare finding
      that is symptomatic to patients and often responds to systemic treatment of
      juvenile dermatomyositis. This is also the first documented case of paracentral
      acute middle maculopathy in the setting of juvenile dermatomyositis. CONCLUSION:
      Chorioretinopathy is a rare finding in juvenile dermatomyositis. While all
      patients with JDM likely do not warrant screening ophthalmologic examinations,
      any patient who has visual symptoms should have a careful dilated examination to
      evaluate for retinopathy or steroid-induced cataracts.

PMID- 28448731
TI  - Differential effects of circadian typology on sleep-related symptoms, physical
      fatigue and psychological well-being in relation to resilience.
AB  - Various physiological and psychological functions are influenced by circadian
      typology (CT), which was reported to be related to resilience. However, few
      studies have assessed the effects of CT in relation to resilience. The aim of the
      present study was to assess the influence of CT on sleep-related symptoms,
      physical fatigue and psychological well-being in relation to resilience. The
      present study included a total of 1794 healthy hospital employees, and they
      completed the Morningness-Eveningness Questionnaire, Connor-Davidson Resilience
      Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Fatigue Severity
      Scale, Hospital Anxiety and Depression Scale and World Health Organization
      Quality of Life Scale Abbreviated Version. Subjects with evening type showed
      lower sleep quality, more daytime sleepiness and physical fatigue than neither
      types and morning types. Additionally, evening types were more depressed and
      anxious and reported a poorer quality of life. CT was found to be a significant
      predictor of sleep quality, but CT was minimally associated with physical fatigue
      and psychological well-being in the regression analysis. Instead, resilience was
      substantially related to all of the variables measured. In conclusion, CT
      independently predicts sleep quality, but the effects of CT on physical fatigue
      and psychological well-being are negligible compared to those of resilience.

PMID- 28448732
TI  - Cytomegalovirus Anterior Uveitis Following Topical Cyclosporine A.
AB  - Cytomegalovirus (CMV) anterior uveitis and endotheliitis occurs among
      immunocompetent individuals and may manifest as Posner-Schlossman syndrome or
      Fuchs uveitis syndrome. The condition may first present following ophthalmic
      surgery, the use of a fluocinolone-sustained steroid drug delivery implant, or
      the use of topical prostaglandin analogues for the treatment of glaucoma. We
      report the first case of a non-human immunodeficiency virus-infected individual
      who presented with CMV anterior uveitis after the use of topical cyclosporine A
      0.05% ophthalmic emulsion for the treatment of symptomatic dry eyes.

PMID- 28448734
TI  - In Response to: "Agrawal R, Oo HH, Balne PK, et al. Zika Virus and the Eye".

PMID- 28448733
TI  - Endogenous Meningococcal Endophthalmitis with Isolated Joint Involvement in
      Immunocompetent Adults.
AB  - PURPOSE: We report two cases of endogenous meningococcal endophthalmitis in
      immunocompetent adults presenting with unilateral ocular disease and joint
      involvement. METHODS: A retrospective review of two patients with endogenous
      endophthalmitis due to Neisseria meningitidis with associated arthropathy was
      conducted. The clinical presentation, investigations, treatment, and outcomes are
      presented. RESULTS: Vitreous sampling confirmed Neisseria meningitidis via
      polymerase chain reaction (PCR) in both cases. PCR was positive from the knee
      aspirate of our second case. Both patients received topical steroids and topical,
      intravitreal and intravenous antibiotics. Despite this, visual outcomes were
      poor. CONCLUSIONS: This atypical combination of endogenous meningococcal
      endophthalmitis associated with meningococcal joint involvement could represent a
      novel pattern for the presentation of metastatic meningococcal endophthalmitis
      not previously described. We suggest joint aspirate PCR could be a useful
      adjunctive test to identify potential causative organisms in such cases where
      there is concurrent joint involvement in the absence of systemic features.

PMID- 28448735
TI  - In response to: Parodi MB, Iacono P, Zucchiatti I, et al. Choroidal
      Neovascularization Associated with Multiple Evanescent White Dot Syndrome Treated
      with Intravitreal Ranibizumab.
AB  - In response to the article by Parodi et al. about choroidal neovascularization
      (CNV) associated with Multiple Evanescent White Dot Syndrome (MEWDS) treated with
      intravitreal Ranibizumab. This article highlights the efficacy of intravitreal
      Ranibizumab in the treatment of CNV associated with MEWDS. In our experience, CNV
      is mostly associated with MEWDS in cases of a wider inflammatory spectrum such as
      overlapping syndrome with multifocal choroiditis (MFC) or punctuate inner
      choroidopathy (PIC). The whole pattern of the case presented in the article is
      compatible with the diagnosis of PIC, meaning that this case described an
      overlapping between MEWDS and PIC diagnoses. Although the authors wrote that CNV
      is secondary to MEWDS, another possible hypothesis is that CNV is secondary to
      PIC. Thus, MEWDS could be secondary to PIC and/or CNV.

PMID- 28448737
TI  - Involvement of ARHGEF10, GEF for RhoA, in Rab6/Rab8-mediating membrane traffic.
AB  - Small GTPases play crucial roles in the maintenance of a homeostatic environment
      and appropriate movements of the cell. In these processes, the direct or indirect
      interaction between distinct small GTPases could be required for regulating
      mutual signaling pathways. In our recent study, ARHGEF10, known as a guanine
      nucleotide exchange factor (GEF) for RhoA, was indicated to interact with Rab6A
      and Rab8A, which are known to function in the exocytotic pathway, and colocalized
      with these Rabs at exocytotic vesicles. Moreover, it was suggested that ARHGEF10
      is involved in the regulation of Rab6A and Rab8A localization and invasion of
      breast carcinoma cells, in which Rab8 also acts via regulation of membrane
      trafficking. These results may reveal the existence of a novel small GTPase
      cascade which connects the signaling of these Rabs with RhoA during membrane
      trafficking. In this mini-review, we consider the possible functions of ARHGEF10
      and RhoA in the Rab6- and Rab8-mediated membrane trafficking pathway.

PMID- 28448736
TI  - Orphan CpG islands define a novel class of highly active enhancers.
AB  - CpG islands (CGI) are critical genomic regulatory elements that support
      transcriptional initiation and are associated with the promoters of most human
      genes. CGI are distinguished from the bulk genome by their high CpG density, lack
      of DNA methylation, and euchromatic features. While CGI are canonically known as
      strong promoters, thousands of 'orphan' CGI lie far from any known transcript,
      leaving their function an open question. We undertook a comprehensive analysis of
      the epigenetic state of orphan CGI across over 100 cell types. Here we show that
      most orphan CGI display the chromatin features of active enhancers (H3K4me1,
      H3K27Ac) in at least one cell type. Relative to classical enhancers, these
      enhancer CGI (ECGI) are stronger, as gauged by chromatin state and in functional
      assays, are more broadly expressed, and are more highly conserved. Likewise, ECGI
      engage in more genomic contacts and are enriched for transcription factor binding
      relative to classical enhancers. In human cancers, these epigenetic differences
      between ECGI vs. classical enhancers manifest in distinct alterations in DNA
      methylation. Thus, ECGI define a class of highly active enhancers, strengthened
      by the broad transcriptional activity, CpG density, hypomethylation, and
      chromatin features they share with promoter CGI. In addition to indicating a role
      for thousands of orphan CGI, these findings suggests that enhancer activity may
      be an intrinsic function of CGI in general and provides new insights into the
      evolution of enhancers and their epigenetic regulation during development and
      tumorigenesis.

PMID- 28448738
TI  - Site-specific recruitment of epigenetic factors with a modular CRISPR/Cas system.
AB  - Dissecting the complex network of epigenetic modifications requires tools that
      combine precise recognition of DNA sequences with the capability to modify
      epigenetic marks. The CRISPR/Cas system has been proven to be a valuable addition
      to existing methodologies that fulfill these tasks. So far, sequence-specific
      editing of epigenetic modifications such as DNA methylation and histone
      posttranslational modifications relied on direct fusions of enzymatically
      inactivated Cas9 (dCas9) with epigenetic effectors. Here, we report a novel,
      modular system that facilitates the recruitment of any GFP-tagged protein to
      desired genomic loci. By fusing dCas9 to a GFP-binding nanobody (GBP) we
      demonstrate that prevalent epigenetic modifications at mouse major satellite
      repeats can be erased or set de novo by recruiting GFP-coupled catalytic domains
      of TET1 and DNMT3A, respectively. Furthermore, we construct an inducible
      expression system that enables a temporally controlled expression of both GBP
      dCas9 and the effector protein. Thus, our approach further expands the CRISPR/Cas
      toolbox for site-specific manipulation of epigenetic modifications with a modular
      and easy-to-use system.

PMID- 28448739
TI  - Health economic evaluation of immunization strategies of hepatitis E vaccine for
      elderly population.
AB  - Objective This study was conducted to assess the cost-effectiveness of hepatitis
      E vaccination of elderly population in the sporadic regions in China. Methods We
      used a decision tree-Markov model to evaluate the cost-effectiveness of 3 kinds
      of hepatitis E virus vaccination strategies from societal perspectives. Parameter
      estimates were obtained from published researches and experts' opinion. The time
      horizon was 16 years, and the discounted rate was 3% annually. Costs are
      expressed in 2016 US dollars. Results The universal vaccination strategy had an
      incremental cost-effectiveness ratio (ICER) of US$ 8475.90 per QALY gained versus
      no vaccination. The implementation of screening and vaccination strategy would
      have an ICER of US$ 4044.28, compared with no vaccination. The vaccination was
      cost-effective (ICER< 3 times China's per capital gross domestic product/quality
      adjusted life years). The QALY of asymptomatic infection, vaccine coverage and
      vaccine protection are the important parameters impacting the ICER in one-way
      sensitivity analysis and screening and vaccination being the dominant strategy in
      probabilistic sensitivity analysis. Conclusion This analysis indicates that
      screening and vaccination is the most cost-effective hepatitis E intervention
      strategy of elderly population in sporadic region in China.

PMID- 28448740
TI  - Sequencing on the SOLiD 5500xl System - in-depth characterization of the GC bias.
AB  - Different types of sequencing biases have been described and subsequently
      improved for a variety of sequencing systems, mostly focusing on the widely used
      Illumina systems. Similar studies are missing for the SOLiD 5500xl system, a
      sequencer which produced many data sets available to researchers today.
      Describing and understanding the bias is important to accurately interpret and
      integrate these published data in various ongoing research projects. We report a
      particularly strong GC bias for this sequencing system when analyzing a defined
      gDNA mix of 5 microbes with a wide range of different GC contents (20-72%) when
      comparing to the expected distribution and Illumina MiSeq data from the same DNA
      pool. Since we observed this bias already under PCR-free conditions, changing the
      PCR conditions during library preparation - a common strategy to handle bias in
      the Illumina system - was not relevant. Source of the bias appeared to be an
      uneven heat distribution during the SOLiD emulsion PCR (ePCR) - for enrichment of
      libraries prior loading - since ePCR in either small pouches or in 96-well plates
      improved the GC bias. Sequencing of chromatin immunoprecipitated DNA (ChIP-seq)
      is a common approach in epigenetics. ChIP-seq of the mixed source histone mark
      H3K9ac (acetyl Histone H3 lysine 9), typically found on promoter regions and on
      gene bodies, including CpG islands, performed on a SOLiD 5500xl machine, resulted
      in major loss of reads at GC rich loci (GC content >= 62%), not explained by low
      sequencing depth. This was improved with adaptations of the ePCR.

PMID- 28448741
TI  - Chromophore attachment to fusion protein of streptavidin and recombinant
      allophycocyanin alpha subunit.
AB  - The fusion protein (SLA) of streptavidin and allophycocyanin alpha subunit (holo
      ApcA) was biosynthesized in Escherichia coli by a dual plasmid system. The
      recombinant SLA, purified by affinity chromatography, showed spectral properties
      similar to natural allophycocyanin alpha subunit (ApcA). Spectral and Zinc
      staining analysis indicated that the recombinant SLA covalently bound
      phycocyanobilin (PCB). To improve chromophorylation rate of recombinant SLA, an
      in vitro chromophore attachment reaction system was established, which contained
      partially chromophylated SLA, PCB and lyase CpcS. Spectral analysis showed that
      PCB bound to the recombinant SLA rapidly during the reaction. The
      chromophorylation rate of SLA was improved from 21.1% to 86.5%.
      Immunofluorescence assay showed that SLA with high chromophorylation rate had
      higher detection signal. Thus, in vitro chromophore attachment is an effective
      way to improve the chromophorylation rate of recombinant phycobiliprotein.

PMID- 28448742
TI  - Choreography of parental histones in damaged chromatin.
AB  - In the cell nucleus, DNA repair machineries operate on a chromatin substrate,
      whose integrity is key for preserving cell functions and identity. Yet, it is
      still unclear how the epigenetic information conveyed by chromatin is maintained
      during the DNA repair process. We recently characterized the dynamics of parental
      histones coupled to UV-C damage repair in human cells, providing insights into
      how the pre-damage chromatin state may be restored. Here, we summarize our main
      findings and discuss them in the context of epigenome maintenance following DNA
      damage. We further address the mechanistic aspects of repair-coupled histone
      dynamics and develop working hypotheses regarding their functional relevance in
      the cellular response to genotoxic stress.

PMID- 28448743
TI  - Circular RNAs with hammerhead ribozymes encoded in eukaryotic genomes: The enemy
      at home.
AB  - A new family of non-autonomous retrotransposons with self-cleaving hammerhead
      ribozymes, the so called retrozymes, has recently been found encoded in diverse
      plant genomes. These retroelements can be actively transcribed, and their RNAs
      accumulate in the cells as abundant non-coding circular RNAs (circRNAs) of small
      size (600-1000 nt). Related circRNAs with self-cleaving ribozymes had already
      been described in plants, and belong to a group of infectious RNA agents with an
      uncertain origin: the viroids and viroid-like satellites of plant RNA viruses.
      These pathogenic circRNAs show many structural similarities with retrozyme
      circRNAs, and both have been found to occur in flowering plants as heterogeneous
      RNA molecules of positive and negative polarities. Taking all these data
      together, we hypothesize that circRNAs encoded by genomic retrozymes could have
      given origin to infectious circRNAs with self-cleaving ribozymes. Moreover, we
      propose that retrozymes in time could have evolved from the ancient family of
      Penelope-like retroelements, which also harbour hammerhead ribozymes. Putative
      retrozyme sequences with hammerhead ribozymes have been detected as well in
      metazoan genomes, opening the door to a common occurrence of circRNAs with self
      cleaving motifs among eukaryotes.

PMID- 28448745
TI  - Medium optimization for pyrroloquinoline quinone (PQQ) production by
      Methylobacillus sp. zju323 using response surface methodology and artificial
      neural network-genetic algorithm.
AB  - Methylobacillus sp. zju323 was adopted to improve the biosynthesis of
      pyrroloquinoline quinone (PQQ) by systematic optimization of the fermentation
      medium. The Plackett-Burman design was implemented to screen for the key medium
      components for the PQQ production. CoCl2 . 6H2O, rho-amino benzoic acid, and
      MgSO4 . 7H2O were found capable of enhancing the PQQ production most
      significantly. A five-level three-factor central composite design was used to
      investigate the direct and interactive effects of these variables. Both response
      surface methodology (RSM) and artificial neural network-genetic algorithm (ANN
      GA) were used to predict the PQQ production and to optimize the medium
      composition. The results showed that the medium optimized by ANN-GA was better
      than that by RSM in maximizing PQQ production and the experimental PQQ
      concentration in the ANN-GA-optimized medium was improved by 44.3% compared with
      that in the unoptimized medium. Further study showed that this ANN-GA-optimized
      medium was also effective in improving PQQ production by fed-batch mode, reaching
      the highest PQQ accumulation of 232.0 mg/L, which was about 47.6% increase
      relative to that in the original medium. The present work provided an optimized
      medium and developed a fed-batch strategy which might be potentially applicable
      in industrial PQQ production.

PMID- 28448744
TI  - Plant signals during beetle (Scolytus multistriatus) feeding in American elm
      (Ulmus americana Planch).
AB  - American Elms were devastated by an outbreak of Dutch Elm Disease is caused by
      the fungus Ophiostoma novo-ulmi Brasier that originated in Asia and arrived in
      the early 1900s. In spite of decades of study, the specific mechanisms and
      disease resistance in some trees is not well understood. the fungus is spread by
      several species of bark beetles in the genus Scolytus, during their dispersal and
      feeding. Our objective was to understand elm responses to beetle feeding in the
      absence of the fungus to identify potential resistance mechanisms. A colony of
      Scolytus multistriatus was established from wild-caught beetles and beetles were
      co-incubated with susceptible or resistant American elm varieties in a controlled
      environment chamber. Beetles burrowed into the auxillary meristems of the young
      elm shoots. The trees responded to the beetle damage by a series of spikes in the
      concentration of plant growth regulating compounds, melatonin, serotonin, and
      jasmonic acid. Spikes in melatonin and serotonin represented a 7,000-fold
      increase over resting levels. Spikes in jasmonic acid were about 10-fold higher
      than resting levels with one very large spike observed. Differences were noted
      between susceptible and resistant elms that provide new understanding of plant
      defenses.

PMID- 28448746
TI  - Pharmaceutical chemicals, steroids and xenoestrogens in water, sediments and fish
      from the tidal freshwater Potomac River (Virginia, USA).
AB  - Selected pharmaceutical chemicals, steroids and xenoestrogens (PCSXs) consisting
      of 29 endocrine modulators, therapeutic drugs, pesticides, detergents, plastics,
      and active ingredients in household products were measured in water, riverbed
      sediments and fish collected in a tributary embayment of the Potomac River
      (Hunting Creek, Alexandria, VA, USA) in the vicinity of wastewater discharge. A
      total of 17 PCSXs were found in the Hunting Creek samples, with steroid hormones
      (e.g., progesterone and 17alpha-ethinylestradiol), triclosan, dextromethorphan
      and bisphenol A being the most prominent micropollutants detected.The geospatial
      distribution of the PCSXs in Hunting Creek indicated that the steroids correlated
      with wastewater treatment plant discharge in all matrices, but such an
      association is tentative in Hunting Creek given the complex nature of urban
      sources of PCSXs and hydrodynamics in an urban tidal river. The sediment PCSX
      concentrations correlated with sediment total organic carbon content at all
      sampling sites. For the most part, the PCSXs showed an enrichment in fish tissue
      relative to sediments when concentrations were normalized to lipids and sediment
      organic carbon contents, but the influence of endogenous steroids is also an
      important consideration for these chemicals.

PMID- 28448747
TI  - A hierarchical Bayesian design for randomized Phase II clinical trials with
      multiple groups.
AB  - Enhanced knowledge of the biological and genetic basis of cancer is re-defining
      the target population for new treatments. In oncology, potential targets for a
      new therapeutic agent often include various solid and hematologic malignancies
      that share common signaling pathways. New agents are often tested in multiple
      tumor types across which information can be borrowed. We propose a hierarchical
      Bayesian design (HBD) to simultaneously test a novel agent in multiple groups for
      randomized Phase II clinical trials with binary endpoints. Compared to parallel
      design for individual tumor groups, the HBD has greatly reduced sample size.
      Therefore, this improves efficiency and decreases the financial cost of
      conducting randomized Phase II clinical trials. An R package hbdct has been
      developed to implement the HBD and streamline the sample size calibration.

PMID- 28448748
TI  - Evaluation of humic substances removal from leachates originating from solid
      waste landfills in Rio de Janeiro State, Brazil.
AB  - This study aimed to evaluate the use of coagulation/flocculation and Fenton
      processes for the removal of the recalcitrant component, in particular humic
      substances, from two different leachates generated in the Gericino and Gramacho
      landfills in Rio de Janeiro State (Brazil). A coagulation/flocculation process,
      using FeCl3.6H2O as the coagulant, was applied to the two leachate samples. In
      the case of the leachate from Gericino landfill, the treatment removed 93% of
      color, 71% of TOC, 69% of COD, 76% of HS, 73% of humic acids (HA) and 82% of
      fulvic acids (FA). In addition, there was a 75% reduction in the absorbance at
      254 nm, using 3,000 mg L-1 of coagulant. In the case of the leachate from
      Gramacho landfill, the treatment removed 91% of color, 69% of TOC, 68% of COD,
      77% of HS, 75% of HA and 80% of FA. In addition, there was a 70% reduction in the
      absorbance at 254 nm using the same concentration of coagulant (3,000 mg L-1).
      The Fenton processes, using FeSO4.7H2O and H2O2 in a ratio of 1:5, were also
      applied to the two leachate samples. In the case of the Gericino leachate, the
      Fenton treatment removed 95% of color, 75% of TOC, 68% of COD, 82% of HS, 77% of
      HA and 93% of FA. In addition, there was a 93% reduction in the absorbance at 254
      nm. In the case of the Gramacho leachate, the Fenton treatment removed 93% of
      color, 73% of TOC, 71% of COD, 81% of HS, 76% of HA, 90% of FA, and there was an
      84% reduction in the absorbance at 254 nm. The results of humic substances,
      color, organic matter and aromatic organic matter (absorbance at 254 nm)
      demonstrate that the coagulation/flocculation and Fenton processes were efficient
      in the removal of recalcitrant organic matter from landfill leachates.

PMID- 28448749
TI  - Testing and application of simple semi-analytical models for soil temperature
      estimation and prediction in environmental assessments.
AB  - The ability of various semi-analytical models to predict soil temperature
      profiles in an experimental plot during a 16-year monitoring study for soil
      depths up to 120 cm is evaluated. The models are developed from an analytical
      model by replacing the steady-state soil temperature with easily obtained hourly
      and daily average temperature values. Such values include the hourly air
      temperature, the daily average air temperature, the hourly soil temperature of
      selected soil depths from three daily observations, the daily average of the soil
      temperature profile and the hourly soil temperature for the bottom depth. The
      performance evaluation results show that, in principle, all models exhibit high
      correlation (R2 values in the range 0.85-0.97), indicating a very good agreement
      between measured and predicted values. In addition, error statistics reveal that
      the best performance in terms of Mean Absolute Error (MAE) and Root Mean Square
      Error (RMSE) is the model based on the daily average of the soil temperature
      profile with MAE values in the range of 0-0.4 degrees C and RMSE values in the
      range of 0.1-1.5 degrees C.

PMID- 28448750
TI  - Simultaneous atrazine degradation and E. coli inactivation by simulated solar
      photo-Fenton-like process using persulfate.
AB  - This work evaluated the feasibility of a photo-Fenton-like process using
      persulfate (PS) and ferrous iron (Fe2+) under simulated solar radiation for
      degrading the herbicide atrazine (ATZ, 6-Chloro-N-ethyl-N'-isopropyl-1,3,5
      triazine-2,4-diamine) and inactivating E. coli. Milli Q water, lake water, and
      diluted wastewater effluents were spiked both simultaneously and separately with
      ATZ (4 mg/L) and E. coli (105 CFU/mL), and exposed to treatment. A method for
      determining the average irradiance throughout the water media in the UV(A+B)
      range of the Xe lamp emission was developed for bench-scale experiments. These
      values were used to calculate the UV(A+B) fluences and the solar UV(A+B) energy
      doses per unit of volume (QUV(A+B), kJ/L). The obtained kinetic data were
      presented versus energy dose. Treatment of lake water at near-neutral pH was
      ineffective via the photo-Fenton-like process, attaining only 20% ATZ removal and
      1-log reduction of E. coli. In Milli Q water and wastewater, the complete
      degradation of ATZ in the absence of bacteria was observed at an average energy
      dose of 1.5 kJ/L (60 min), while in the presence of cells the degradation
      efficiency was ~60%. When ATZ was present, E. coli inactivation was also affected
      in Milli Q water, with 1.4-log reduction (93%) at a dose of 1.6 kJ/L (60 min),
      whereas in wastewater complete inactivation was achieved at a lower dose of 1.3
      kJ/L (45 min). The energy requirements on a QUV(A+B) basis for simultaneous 90%
      ATZ removal and 99.99% E. coli inactivation in Milli Q water and wastewater were
      shown to be less than 10 kJ/L. This suggests the solar/PS/Fe2+ system is
      promising for simultaneous treatment and disinfection of wastewater effluents.

PMID- 28448752
TI  - Temperature measurements in a capacitive system of deep loco-regional
      hyperthermia.
AB  - Hyperthermia has been shown to be a medically useful procedure applicable for
      different indications. For the connection between clinical effects and heat, it
      is important to understand the actual temperatures achieved in the tissue. There
      are limited temperature data available when using capacitive hyperthermia devices
      even though this is worldwide the most widespread method for loco-regional
      heating. Hence, this study examines temperature measurements using capacitive
      heating. Bioequivalent phantoms were used for the measurements, which, however,
      do not consider perfusion in live tissue. In general, the required temperature
      impact for an effective cancer therapy should need an increase of 0.2 degrees
      C/min, which has been achieved. In the described tests on the non-perfused dummy,
      on average, the temperature increases by approximately 2 degrees C in the first
      12 min. The temperature difference relative to the starting temperature was 10-12
      degrees C within a therapy time of 60 min (rising from the initial room
      temperature between 20-24 degrees C and 32-34 degrees C). The average deviation
      with three individual measurements each on different days in a specified
      localization was 2 degrees C. The minimum temperature difference was 4.2 degrees
      C, and the maximum value was reached in the liver with 10.5 degrees C. These
      values were achieved with a moderate energy input of 60-150 watts, with much
      higher performance outputs still available. These results show that the tested
      capacitive device is capable of achieving quick temperature increase with a
      sufficient impact into the depth of a body.

PMID- 28448751
TI  - Role of PU.1 Expression as an Inflammatory Marker in Experimental Autoimmune
      Uveoretinitis.
AB  - PURPOSE: PU.1 is an Ets family transcription factor, which is essential for the
      development of immune system through generation of myeloid and lymphoid lineages.
      In this study, we investigated PU.1 expression in the retina of mice with
      experimental autoimmune uveoretinitis (EAU) and the association between PU.1
      expression level and inflammation in EAU. METHODS: IRBP 1-20 peptide-immunized
      mice were used. Quantitative PCR, ELISA analysis, cytometric bead array (CBA),
      assay and immunostaining were conducted using ocular tissues and lymph nodes.
      RESULTS: Quantitative PCR showed significant increases in mRNA levels of PU.1 in
      the retina at the peak of inflammation. Immunostaining of retina flat mounts
      revealed that most PU.1-positive cells were co-stained with anti-CD11c and anti
      F4/80 antibodies. PU.1 knockdown in lymph node cells significantly suppressed
      IRBP-stimulated IFN-gamma production measured by ELISA and IL-2 production
      measured by CBA. CONCLUSION: PU.1 may play crucial roles in the development and
      progression of inflammation in EAU.

PMID- 28448753
TI  - Road traffic injury in sub-Saharan African countries: A systematic review and
      summary of observational studies.
AB  - OBJECTIVE: The aim of this study is to evaluate, through a systematic review of
      hospital-based studies, the proportion of road traffic injuries and fatalities in
      sub-Saharan Africa (SSA). METHODS: In accordance with Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of
      Observational Studies in Epidemiology guidelines, we searched the following
      electronic databases: PubMed, Embase, Africa-Wide Information, Global Health, and
      Web of Science. Articles were eligible if they measured proportion of road
      traffic injuries (RTIs) in SSA by using hospital-based studies. In addition, a
      reference and citation analysis was conducted as well as a data quality
      assessment. RESULTS: Up to 2015, there were a total of 83 hospital-based
      epidemiologic studies, including 310,660 trauma patients and 99,751 RTI cases, in
      13 SSA countries. The median proportion of RTIs among trauma patients was 32% (4
      to 91%), of which the median proportion of death for the included articles was 5%
      (0.3 to 41%). CONCLUSION: The number of studies evaluating RTI proportions and
      fatalities in SSA countries is increasing but without the exponential rise
      expected from World Health Organization calls for research during the Decade of
      Action for Road Traffic Injuries. Further research infrastructure including
      standardization of taxonomy, definitions, and data reporting measures, as well as
      funding, would allow for improved cross-country comparisons.

PMID- 28448754
TI  - CLINICAL EVALUATION OF COST EFFICACY OF DRUGS FOR TREATMENT OF OSTEOPOROSIS: A
      META-ANALYSIS.
AB  - OBJECTIVE: To assess the cost efficacy of available regimens for therapy of
      osteoporosis as defined as the cost time's number need to treat to prevent one
      fracture. METHODS: Existing meta-analyses were supplemented through electronic
      databases SCOPUS and PubMed between 2013 (a date overlapping the latest meta
      analyses) and March 2016. Primary references included all randomized controlled
      trials of anti-osteoporotic drugs versus comparators using search terms
      "osteoporosis," "random," and "trial." RESULTS: There were 43 evaluable
      randomized, double-blind, placebo-controlled trials in 71,809 postmenopausal
      women comparing fracture frequency. Trials were similar in recruitment age (mean
      +/- SD, 67.3 +/- 8.1 years) and follow-up duration (25.5 +/- 12.6 months). Cost
      comparisons were evaluated for a treatment strategy assuming generic alendronate
      as first-line therapy. Denosumab and teriparatide showed benefits in vertebral
      fracture reduction over alendronate at incremental costs respectively of $46,000
      and $455,000 per fracture prevented. Zoledronate, recently released as a generic,
      would be either less expensive or comparable in cost. None of the alternate
      medicines were statistically better in preventing hip fractures. Teriparatide was
      more effective in preventing nonvertebral fractures at an incremental cost of
      $1,555,000. CONCLUSION: The most cost-effective initial therapy of postmenopausal
      osteoporosis is generic oral alendronate or generic parenteral zoledronate. There
      is no statistically significant difference in efficacy of available drugs to
      prevent hip fractures. There are limited data to suggest switching drugs after
      sustaining an osteoporotic fracture while on oral alendronate therapy, although
      generic zoledronate may be considered on the basis of side effects or questions
      of medication adherence. ABBREVIATIONS: ALN = alendronate; DEN = denosumab; IBN =
      ibandronate; NNT = number needed to treat; OR = odds ratio; RCT = randomized
      controlled trial; RIS = risedronate; RLN = raloxifene; TER = teriparatide; ZOL =
      zoledronate.

PMID- 28448755
TI  - VISUAL VIGNETTE.

PMID- 28448756
TI  - BARIATRIC ENDOCRINOLOGY AND VERY-LOW-CALORIE MEAL PLANS.
AB  - ABBREVIATIONS: PSMF = protein-sparing modified fast; VLCMP = very-low-calorie
      meal plans.

PMID- 28448757
TI  - PREVALENCE AND TYPES OF GENDER-AFFIRMING SURGERY AMONG A SAMPLE OF TRANSGENDER
      ENDOCRINOLOGY PATIENTS PRIOR TO STATE EXPANSION OF INSURANCE COVERAGE.
AB  - OBJECTIVE: Transgender individuals now have many options for medical
      intervention, including gender-affirmation surgeries. However, it is unknown how
      common it is for transgender individuals to undergo these surgeries. The purpose
      of this cross-sectional study was to assess the prevalence of gender-affirming
      surgeries among transgender patients in 2015, which was immediately prior to
      insurance changes that made gender-affirming surgery more affordable for
      Massachusetts residents. METHODS: A retrospective chart review of 99 transgender
      patients was performed at the Endocrinology Clinic at Boston Medical Center, an
      urban safety net hospital. The records for 99 transgender subjects who received
      treatment between 2004-2015, including 28 transmen and 71 transwomen, were
      examined. The outcome measures were the types of medical interventions chosen by
      transgender patients, which included hormone therapy, chest surgery, gonadectomy,
      genital surgery, and facial surgery. RESULTS: Thirty-five percent of subjects had
      undergone at least one gender-affirming surgery. Transmen were more likely to
      have had surgery than transwomen (54% vs. 28%). Twenty-five percent of patients
      had chest surgery, 13% had genital surgery or gonadectomy, and 8% had facial
      surgery. CONCLUSION: In 2015, a majority of transgender endocrinology clinic
      patients had not undergone any type of gender-affirmation surgery. Among those
      who did elect to have a surgery, genital surgery or gonadectomy were uncommon.
      The low rate of surgery among this sample of transgender patients may be
      attributable to the financial cost, lack of interest in surgery, or that genital
      surgery is not a high priority for transgender individuals relative to surgery to
      change visible features such as face and chest. Abbreviation: HT = hormone
      therapy.

PMID- 28448758
TI  - VISUAL VIGNETTE.

PMID- 28448759
TI  - FT3 IS HIGHER IN MALES THAN IN FEMALES AND DECREASES OVER THE LIFESPAN.
AB  - OBJECTIVE: Normal changes in free triiodothyronine (FT3), free thyroxine (FT4),
      and thyroid-stimulating hormone (TSH) levels over the lifespan and differences
      between sexes are not well documented, mainly because even the largest-scale
      studies available include relatively small cohorts. The aim of this study was to
      define age-related trends including sex differences based on reliable data.
      METHODS: A large database including serum thyroid tests drawn in community
      clinics was studied. FT3, FT4, and TSH levels from 527,564 sera samples taken
      from patients age 1 year or greater were included. After highly extensive
      exclusion criteria applied to remove all samples that may have been taken from
      unhealthy people, 27,940 samples remained. These were stratified by decades of
      age and by sex. RESULTS: FT3 decreases throughout life, significantly more so
      among females, with equalization between sexes with greater age. FT4 declines to
      a lesser extent, also more among females than among males. Among the very old,
      females have higher levels of FT4. In contrast, TSH declines until age 50 and
      then increases slightly in both sexes. CONCLUSION: This study provides reliable
      data regarding trends in hormonal levels by age and sex, with the major finding
      being higher FT3 in males throughout life except in the very young and very old.
      These results have important implications for diagnosing and treating thyroid
      conditions. ABBREVIATIONS: ANOVA = analysis of variance; BMI = body mass index;
      FT3 = free triiodothyronine; FT4 = free thyroxine.

PMID- 28448760
TI  - ANABOLIC BONE WINDOW WITH WEEKLY TERIPARATIDE THERAPY IN POSTMENOPAUSAL
      OSTEOPOROSIS.

PMID- 28448761
TI  - SLEEPING CUPID BY CARAVAGGIO: WHAT DIAGNOSIS?
AB  - OBJECTIVE: The Sleeping Cupid, by Italian painter Caravaggio is a masterpiece
      painted in 1608. Signs of an endocrine disease are hidden among the shadows of
      the painting. We decided to conduct a survey among endocrinologists practicing in
      Italy and asked them if they could identify a specific disease condition in
      Caravaggio's Sleeping Cupid. METHODS: A total of 86 members from 2 Italian
      endocrine societies completed the survey: 67 from the Society of Endocrinology
      and 19 from the Society of Paediatric Endocrinology and Diabetology. RESULTS:
      Altogether 21 (24.4%) endocrinologists agreed the Sleeping Cupid was affected by
      hypopituitarism, 30 (34.9%) diagnosed rickets, 15 (17.4%) identified a SHOX gene
      defect, 16 (18.6%) did not agree on any of the suggested hypotheses, and 4 (4.6%)
      endocrinologists could not identify any disease. The perception looking at a
      painting can never be entirely similar to that of another person, even though a
      commonality of features may instead indicate the opposite. That must be the
      reason why, within a group of Italian endocrinologists who analyzed Caravaggio's
      Sleeping Cupid, pediatric endocrinologists (who see in their clinical practice
      exclusively children and teenagers) considered rickets as their first choice of
      diagnosis, whereas the majority of adult endocrinologists suggested
      hypopituitarism. CONCLUSION: In conclusion, as Walter Benjamin said "to arrive at
      the purity of the gaze is not difficult, it is impossible."

PMID- 28448762
TI  - BONE TURNOVER IN OSTEOPOROTIC WOMEN DURING LONG-TERM ORAL BISPHOSPHONATES
      TREATMENT: IMPLICATIONS FOR TREATMENT FAILURE AND "DRUG HOLIDAY" IN THE REAL
      WORLD.
AB  - OBJECTIVE: Little data exist to support concerns over bone turnover suppression
      during prolonged oral bisphosphonate treatment and on consequences of the
      recommended "drug holiday." This study was performed to assess bone resorption
      rates in postmenopausal osteoporotic women on prolonged oral bisphosphonate
      treatment and in response to switching to "drug holiday" intravenous
      bisphosphonate, or continuation of oral bisphosphonates. METHODS: The frequency
      distribution of the bone resorption marker urinary deoxypyridinoline crosslinks
      (uDPD), was obtained retrospectively from 211 osteoporotic women attended at an
      academic hospital endocrine clinic, treated for >2 years with oral
      bisphosphonates. In some patients, uDPD was re-assessed following modification or
      continuation of treatment. RESULTS: The mean duration of oral bisphosphonates
      treatment was 7.2 +/- 3.1 years. uDPD was within reference range for
      premenopausal women in 61.6% of the patients, below in 7.6% of the patients, and
      above upper limit in 30.8%. uDPD decreased significantly following intravenous
      zoledronic acid, increased significantly during "drug holiday," and slightly
      decreased in those continued on oral bisphosphonate treatment. CONCLUSION: In
      this real-world study, the majority of women on prolonged oral bisphosphonates
      maintained bone resorption rates within the normal reference range for
      premenopausal women. The likelihood for inadequate suppression was considerably
      greater than that of over-suppression. Implementing a "drug holiday" resulted in
      a marked increase in bone resorption rates. Additional studies should explore the
      potential role of bone turnover markers in the evaluation of patients on
      prolonged oral bisphosphonates and during "drug holiday" in different settings
      and using additional markers. ABBREVIATIONS: BMD = bone mineral density; IQR =
      interquartile range; uDPD = urinary deoxypyridinoline crosslinks.

PMID- 28448763
TI  - ANALYSIS OF POSTOPERATIVE ULTRASONOGRAPHY SURVEILLANCE AFTER HEMITHYROIDECTOMY IN
      PATIENTS WITH PAPILLARY THYROID MICROCARCINOMA: A MULTICENTER STUDY.
AB  - OBJECTIVE: The optimal follow-up interval for postoperative ultrasonography (US)
      surveillance after hemithyroidectomy in patients with papillary thyroid
      microcarcinoma (PTMC) is unclear. The purpose of this study was to evaluate the
      prevalence of tumor recurrence/persistence and to investigate the appropriateness
      of postoperative US surveillance in PTMC patients who underwent
      hemithyroidectomy. METHODS: Our institutional review board approved this
      retrospective study. From 2000 to 2011, 800 patients underwent hemithyroidectomy
      as treatment for PTMC, as well as at least one session of postoperative follow-up
      US, at four different institutions. The images and data of postoperative US
      surveillance were retrospectively investigated by experienced radiologists at
      each institution. Based on the follow-up US and histopathologic results,
      locoregional tumor recurrence/persistence was determined. RESULTS: Of the 800
      patients, 82.2% had T1a, 17.8% had T3, and none had T1b, T2, T4a, or T4b disease;
      6.9% had unknown N stage, 80.1% had N0, 13% had N1a, and none had N1b, based on
      histopathology. There were also no cases of distant metastasis after
      hemithyroidectomy. Among the patients, 784 (98%) showed no tumor
      recurrence/persistence, and 16 (2%) showed locoregional tumor
      recurrence/persistence during the follow-up period. The patients differed in the
      number of sessions and the intervals of postoperative follow-up US. In the 16
      patients with tumor recurrence/persistence, the mean interval of postoperative
      follow-up US since the first US detection of tumor recurrence/persistence was
      42.9 +/- 25.9 months. All recurrence/persistence cases were subcentimeter.
      CONCLUSION: Postoperative US surveillance at 1-or 2-year intervals may be
      unnecessary because of the very low recurrence rate in PTMC. ABBREVIATIONS: EMR =
      electronic medical record; PTMC = papillary thyroid microcarcinoma; TNM = tumor,
      node, metastasis; US = ultrasonography; US-FNA = ultrasonography-guided fine
      needle aspiration.

PMID- 28448764
TI  - MECHANISTIC INSIGHTS INTO OSTEOPOROSIS IN PATIENTS WITH LIPODYSTROPHY AND REVIEW
      OF THE LITERATURE.
AB  - OBJECTIVE: To demonstrate the underlying pathogenesis of osteoporosis occurring
      in patients with lipodystrophy. METHODS: MEDLINE was searched using the following
      key terms: lipodystrophy, osteoporosis, and reduced bone mineral density. Manual
      searching identified additional studies from the bibliographies of reports and
      reviews obtained in the MEDLINE search. RESULTS: Lipodystrophy is a very rare
      disease characterized by pathologic alterations in the distribution of adipose
      tissues in association with a diverse range of metabolic derangements such as
      hypertriglyceridemia, insulin resistance, diabetes, and abnormal bone formation.
      Reduced bone mineral density has been assessed extensively in human
      immunodeficiency virus-infected patients with lipodystrophy, but far less is
      known in other lipodystrophy types. This is the first review to discuss the
      mechanisms of osteoporosis occurrence in various types of lipodystrophy. We
      herein focus on the cross-regulation of fat and bone and propose that marrow fat
      accumulation and reduced serum leptin and adiponectin levels may play important
      roles in the pathophysiologic process of osteoporosis in patients with
      lipodystrophy. CONCLUSION: Osteoporosis is an emerging threat to patients with
      lipodystrophy. When evaluating the clinical course of a patient with
      lipodystrophy, osteoporosis should also be considered. ABBREVIATIONS: BMD = bone
      mineral density; CGL = congenital generalized lipodystrophy; HIV = human
      immunodeficiency virus; MAT = marrow adipose tissue; OB-R = leptin receptor.

PMID- 28448765
TI  - Digital Assays Part I: Partitioning Statistics and Digital PCR.
AB  - A digital assay is one in which the sample is partitioned into many small
      containers such that each partition contains a discrete number of biological
      entities (0, 1, 2, 3, ...). A powerful technique in the biologist's toolkit,
      digital assays bring a new level of precision in quantifying nucleic acids,
      measuring proteins and their enzymatic activity, and probing single-cell
      genotypes and phenotypes. Part I of this review begins with the benefits and
      Poisson statistics of partitioning, including sources of error. The remainder
      focuses on digital PCR (dPCR) for quantification of nucleic acids. We discuss
      five commercial instruments that partition samples into physically isolated
      chambers (cdPCR) or droplet emulsions (ddPCR). We compare the strengths of dPCR
      (absolute quantitation, precision, and ability to detect rare or mutant targets)
      with those of its predecessor, quantitative real-time PCR (dynamic range, larger
      sample volumes, and throughput). Lastly, we describe several promising
      applications of dPCR, including copy number variation, quantitation of
      circulating tumor DNA and viral load, RNA/miRNA quantitation with reverse
      transcription dPCR, and library preparation for next-generation sequencing. This
      review is intended to give a broad perspective to scientists interested in
      adopting digital assays into their workflows. Part II focuses on digital protein
      and cell assays.

PMID- 28448766
TI  - Cross-linguistic adaptations of The Comprehensive Aphasia Test: Challenges and
      solutions.
AB  - Comparative research on aphasia and aphasia rehabilitation is challenged by the
      lack of comparable assessment tools across different languages. In English, a
      large array of tools is available, while in most other languages, the selection
      is more limited. Importantly, assessment tools are often simple translations and
      do not take into consideration specific linguistic and psycholinguistic
      parameters of the target languages. As a first step in meeting the needs for
      comparable assessment tools, the Comprehensive Aphasia Test is currently being
      adapted into a number of languages spoken in Europe. In this article, some key
      challenges encountered in the adaptation process and the solutions to ensure that
      the resulting assessment tools are linguistically and culturally equivalent, are
      proposed. Specifically, we focus on challenges and solutions related to the use
      of imageability, frequency, word length, spelling-to-sound regularity and
      sentence length and complexity as underlying properties in the selection of the
      testing material.

PMID- 28448767
TI  - Transcriptional control of yeast ribosome biogenesis: A multifaceted role for
      general regulatory factors.
AB  - In Saccharomyces cerevisiae, a group of more than 200 co-regulated genes (Ribi
      genes) is involved in ribosome biogenesis. This regulon has recently been shown
      to rely on a small set of transcriptional regulators (mainly Abf1, but also Reb1,
      Tbf1 and Rap1) previously referred to as general regulatory factors (GRFs)
      because of their widespread binding and action at many promoters and other
      specialized genomic regions. Intriguingly, Abf1 binding to Ribi genes is
      differentially modulated in response to distinct nutrition signaling pathways.
      Such a dynamic promoter association has the potential to orchestrate both
      activation and repression of Ribi genes in synergy with neighboring regulatory
      sites and through the functional interplay of histone acetyltransferases and
      deacetylases.

PMID- 28448768
TI  - Toxicity identification and evaluation (TIE) of a petroleum refinery wastewater.
AB  - Petroleum refineries generate large amounts of wastewaters, which can have
      acute/chronic toxicity toward aquatic organisms. Previous studies have shown that
      many contaminants can be responsible for this toxicity, among them ammonia,
      sulfide, cyanide, phenols and hydrocarbons. In the study reported herein, the
      cause of the chronic toxicity of a biotreated petroleum refinery wastewater was
      investigated by applying the TIE methodology using the microcrustacean
      Ceriodaphnia dubia. Five samples were analyzed, and the results suggest that
      copper is the primary toxicant, showing a strong correlation with wastewater
      toxicity in Phase III. Other metal contaminants, such as zinc and nickel, are
      present in the samples at toxic concentrations and these may also contribute (to
      a lesser degree) toward the toxicity. In the case of one sample, the toxicity was
      attributed to polycyclic aromatic hydrocarbons (PAHs), possibly benzo(a)pyrene,
      which was present at a concentration toxic to C. dubia. Although the values for
      the physicochemical parameters of the samples were below Brazilian environmental
      regulation limits (CONAMA 430), this was not sufficient to prevent chronic
      toxicity toward aquatic life, indicating that these limits are relatively high.

PMID- 28448769
TI  - Dental Therapists: A Solution to a Shortage of Dentists in Underserved
      Communities?

PMID- 28448771
TI  - Geosmithia associated with bark beetles and woodborers in the western USA:
      taxonomic diversity and vector specificity.
AB  - Fungi in the genus Geosmithia (Ascomycota: Hypocreales) are frequent associates
      of bark beetles and woodborers that colonize hardwood and coniferous trees. One
      species, Geosmithia morbida, is an economically damaging invasive species. The
      authors surveyed the Geosmithia species of California and Colorado, USA, to (i)
      provide baseline data on taxonomy of Geosmithia and beetle vector specificity
      across the western USA; (ii) investigate the subcortical beetle fauna for
      alternative vectors of the invasive G. morbida; and (iii) interpret the community
      composition of this region within the emerging global biogeography of Geosmithia.
      Geosmithia was detected in 87% of 126 beetle samples obtained from 39 plant
      species. Twenty-nine species of Geosmithia were distinguished, of which 13 may be
      new species. Bark beetles from hardwoods, Cupressus, and Sequoia appear to be
      regular vectors, with Geosmithia present in all beetle gallery systems examined.
      Other subcortical insects appear to vector Geosmithia at lower frequencies.
      Overall, most Geosmithia have a distinct level of vector specificity (mostly
      high, sometimes low) enabling their separation to generalists and specialists.
      Plant pathogenic Geosmithia morbida was not found in association with any other
      beetle besides Pityophthorus juglandis. However, four additional Geosmithia
      species were found in P. juglandis galleries. When integrated with recent data
      from other continents, a global pattern of Geosmithia distribution across
      continents, latitudes, and vectors is emerging: of the 29 Geosmithia species
      found in the western USA, 12 have not been reported outside of the USA. The most
      frequently encountered species with the widest global distribution also had the
      broadest range of beetle vectors. Several Geosmithia spp. with very narrow vector
      ranges in Europe exhibited the similar degree of specialization in the USA. Such
      strong canalization in association could reflect an ancient origin of each
      individual association, or a recent origin and a subsequent diversification in
      North America.

PMID- 28448773
TI  - Letter--Prudent Formulary Management or Underutilization of the Novel P2Y12
      Receptor Inhibitors in Patients with Acute Coronary Syndrome Who Received
      Percutaneous Coronary Intervention?
AB  - DISCLOSURES: The author is a former employee of AstraZeneca and owns stock in
      AstraZeneca. The author reports no conflicts of interest related to the subject
      of this letter.

PMID- 28448772
TI  - The Effect of a Federal Controlled Substance Act Schedule Change on Hydrocodone
      Combination Products Claims in a Medicaid Population.
AB  - BACKGROUND: In 2012, hydrocodone combination products (HCPs) were the most
      prescribed medications in the United States. Under the Controlled Substance Act
      of 1970, hydrocodone alone was classified as a Schedule II drug, while HCPs were
      classified as Schedule III, indicating a lower risk for abuse and misuse.
      However, according to a Drug Enforcement Agency analysis, the addition of
      nonopioids has not been shown to diminish abuse potential of hydrocodone. In
      response to concerns for drug abuse and overdose, the Drug Enforcement Agency
      rescheduled HCPs to Schedule II in October 2014, with the intent of limiting
      overprescribing and increasing awareness of their abuse potential. However, it is
      unknown whether this has affected the overall claims for HCPs in a Medicaid
      population. OBJECTIVES: To (a) compare the trend in HCP prescription claims with
      select non-HCP (opioid and nonopioid) analgesic claims before and after the HCP
      schedule change in the Massachusetts Medicaid fee-for-service/Primary Care
      Clinician plan population and (b) identify if there was a change in HCP new start
      member and claim characteristics before and after the HCP schedule change.
      METHODS: This quasi-experimental, retrospective study used enrollment and
      pharmacy claims data to evaluate all members in the study population 1 year
      before and after the HCP schedule change. The number of claims for HCPs and
      select non-HCP analgesics was reported as the monthly rate per total population,
      and an interrupted time series analysis compared the change in the monthly rate
      of claims across groups. Members with 1 or more pharmacy claims for a new HCP
      prescription during a 5-month period before or after the HCP schedule change were
      analyzed to determine member demographics (age, gender, and number of claims) and
      claim characteristics (average daily dose, average quantity per claim, and days
      supply). RESULTS: The rate of HCP claims increased before and decreased after the
      HCP schedule change. Controlling for the trend during the period before the HCP
      schedule change, the rate of HCP claims per 1,000 members per month decreased at
      a greater rate than non-HCP analgesics in the period after the HCP schedule
      change (P < 0.001). The percentage of HCP claims for new start members decreased
      after the HCP schedule change (44.9% vs. 34.1% of all HCP claims pre- to post
      schedule change; P < 0.001). In the group of new starts, there was not a
      significant difference in the average daily dose (26.3 mg vs. 26.4 mg; P = 0.69),
      while there was a decrease in average number of tablets dispensed per claim (from
      37.1 to 20.3 tablets; P < 0.001) and an increase in the percentage of claims for
      a shorter days supply (from 57.7% to 81.6%; P < 0.001). CONCLUSIONS: The findings
      of this study suggest that the HCP schedule change may have contributed to the
      decrease in claims for HCPs in a Medicaid population. After the HCP schedule
      change, there was a trend towards decreased HCP use among new starts.
      DISCLOSURES: No outside funding supported this study. The authors have nothing to
      disclose. Study concept and design were contributed by all authors except for
      Arnold and Clements. Tran, Arnold, and Clements took the lead in data collection,
      along with Peristere, and data interpretation was performed by all the authors,
      except Arnold. The manuscript was written primarily by Tran, along with Lavitas,
      Stevens, and Greenwood, and revised by all the authors except Arnold and
      Peristere. A poster of this research project was presented at the Academy of
      Managed Care Pharmacy's 2016 Annual Meeting in San Francisco, California, April
      2016.

PMID- 28448774
TI  - Letter--The Authors Respond.
AB  - DISCLOSURES: None of the authors of this study are involved in financial or
      personal relationships with agencies, institutions, or organizations that
      inappropriately influenced the statistical analysis plan or interpretation of the
      study results. DiDomenico received an honorarium from Amgen for the preparation
      of a heart failure drug monograph for Pharmacy Practice News and was a
      coinvestigator on funded research for the Patient-Centered Outcomes Research
      Institute. DiDomenico also serves as an advisory board member for a heart failure
      program at Otsuka America Pharmaceuticals and as an advisory board member at
      Novartis Pharmaceuticals. Touchette has received unrestricted grant funding from
      Cardinal Health and Sunovion Pharmaceuticals and has also served as a consultant
      to, and director of, the American College of Clinical Pharmacy Practice-Based
      Research Network on a study funded by Pfizer.

PMID- 28448776
TI  - Corrections.

PMID- 28448775
TI  - Exploring Electronic Medical Record and Self-Administered Medication Risk
      Screening Tools in a Primary Care Clinic.
AB  - BACKGROUND: Electronic medical record (EMR) screening for indicators of
      medication risk could improve efficiency in identifying primary care clinic
      patients in need of clinical pharmacist care compared with patient self
      reporting. OBJECTIVES: To (a) compare the performance of an EMR medication risk
      assessment questionnaire (MRAQ) with a self-administered (SA) MRAQ and (b)
      explore each tool's ability to predict indicators of health behavior, health
      status, and health care utilization. METHODS: A prospective cohort study was
      conducted with 143 adults who attended an academic family medicine center and
      were taking >= 2 medications. All participants completed the 10-item SA-MRAQ,
      Morisky Medication Adherence Scale, Chew's health literacy screener, Stanford
      Health Distress Scale, and SF-36 overall rating of health. A blinded investigator
      completed the EMR-MRAQ and a chart review to ascertain 6 months of health care
      utilization. Outcome measures included the following: (a) scores from the 5- and
      10-item SA-MRAQs and 5-item EMR-MRAQ; (b) sensitivity and specificity to
      determine the accuracy of the 5-item EMR versus the 5-item SA risk scores; (c)
      correlations between risk assessments and health behavior/status scales; and (d)
      area under the receiver operator curve to determine how well a high-risk score
      predicted health care utilization. RESULTS: The 5-item SA-MRAQ, the 5-item EMR
      MRAQ, and the 10-item SA-MRAQ categorized 52.9% (55/104), 69.2% (99/143), and
      17.6% (18/102) of participants as high risk, respectively. For the 104
      participants who completed both 5-item MRAQ tools, the EMR-MRAQ had a sensitivity
      of 81.8% and specificity of 49.0% in detecting a high-risk SA-MRAQ score. Both 5
      item risk assessments showed weak correlations with health distress and overall
      health, while the 10-item SA-MRAQ additionally showed weak correlations with
      medication adherence. The EMR-MRAQ was most effective in predicting all-cause
      emergency room visits/hospitalization (c-statistic = 0.69; 95% CI=0.57-0.81) and
      high clinic utilization (>= 4 visits per 6 months; c-statistic = 0.77; 95% CI =
      0.69-0.85). The EMR-MRAQ had high sensitivities but low specificities for these
      health care utilization outcomes, respectively (82.6% and 33.3%; 88.9% and
      42.7%). CONCLUSIONS: This pilot study suggests that EMR-MRAQ screening has high
      sensitivity but low specificity in comparison with self-reporting and was able to
      discriminate between those who would and would not experience health care
      utilization outcomes. These results justify further development and validation of
      an automated EMR-based tool to predict patient-important consequences of
      medication-related problems. DISCLOSURES: This work was funded by the Canadian
      Society of Hospital Pharmacists Research and Education Foundation, which had no
      role in the analysis or interpretation of data or the decision to submit the
      manuscript for publication. The authors have no conflict of interests, potential
      or otherwise, to report. Makowsky had full access to all of the data in the study
      and takes responsibility for the integrity of the data and the accuracy of the
      data analysis. Study concept and design were contributed by Makowsky and Cor.
      Makowsky and Wong collected the data, and data interpretation was performed by
      Makowsky, Cor, and Wong. The manuscript was written by Makowsky and was
      critically reviewed for intellectual content by Makowsky, Cor, and Wong.

PMID- 28448777
TI  - Effect of an Advanced Pharmacy Practice Experience on Medication Therapy
      Management Services in a Centralized Retail Pharmacy Program.
AB  - BACKGROUND: Medication therapy management (MTM) delivery is increasingly
      important in managed care. Successful delivery positively affects patient health
      and improves Centers for Medicare & Medicaid Services star ratings, a measure of
      health plan quality. As MTM services continue to grow, there is an increased need
      for efficient and effective care models. The primary objectives of this project
      were to describe the delivery of MTM services by fourth-year Advanced Pharmacy
      Practice Experience (APPE) students in a centralized retail pharmacy system and
      to evaluate and quantify the clinical and financial contributions of the
      students. The secondary objective was to describe the engagement needed to
      complete comprehensive medication reviews (CMRs) and targeted interventions.
      PROGRAM DESCRIPTION: From May 2015 to December 2015, thirty-five APPE students
      from the University of Colorado Skaggs School of Pharmacy provided MTM services
      at Albertsons Companies using the OutcomesMTM and Mirixa platforms. Students
      delivered patient care services by phone at the central office and provided face
      to-face visits at pharmacies in the region. With implementation of the MTM APPE
      in 2015, the team consisted of 2 MTM pharmacists and pharmacy students, as
      compared with 1 MTM pharmacist in 2014. The number of CMRs and targeted
      interventions completed and the estimated additional revenue generated during the
      2015 time period were compared with those completed from May through December
      2014. The patient and provider engagement needed to complete the CMRs and
      targeted interventions was summarized. OBSERVATIONS: 125 CMRs and 1,918 targeted
      interventions were billed in 2015, compared with 13 CMRs and 767 targeted
      interventions in 2014. An estimated $16,575-$49,272 of additional revenue was
      generated in 2015. To complete the interventions in 2015, the team engaged in
      1,714 CMR opportunities and 4,686 targeted intervention opportunities.
      IMPLICATIONS/RECOMMENDATIONS: In this MTM rotation, students provided real-life
      care to patients, resulting in financial and clinical contributions. This model
      of education and care delivery can be replicated in the community pharmacy or
      managed care setting. APPE students are an important component of this model of
      care delivery, particularly when considering the level of patient engagement
      needed to complete MTM interventions. DISCLOSURES: No outside funding supported
      this research. The authors have no conflicts of interest to disclose related to
      this work. All authors contributed to study concept and design. Rodgers collected
      the data, and data interpretation was performed by Vande Griend, along with
      Rodgers and Nuffer. The manuscript was written and revised primarily by Vande
      Griend, along with Nuffer and Rodgers. This project was presented at the Pharmacy
      Quality Alliance Annual Meeting in Arlington, Virginia, in May 2016.

PMID- 28448778
TI  - Economic Impact of Above-Label Dosing with Etanercept, Adalimumab, or Ustekinumab
      in Patients with Psoriasis.
AB  - BACKGROUND: Patients with moderate-to-severe psoriasis may be treated with above
      label doses of biologics in an attempt to optimize outcomes. Dose escalation will
      have an effect on the cost of treatment. OBJECTIVE: To examine costs related to
      above-label use of etanercept, adalimumab, and ustekinumab among patients with
      moderate-to-severe psoriasis. METHODS: A retrospective study was performed using
      a large U.S. claims database. Patients were included in the study if they were
      aged >= 18 years with a diagnosis of psoriasis (excluding psoriatic arthritis)
      and had at least 1 medication fill for etanercept, adalimumab, or ustekinumab
      between January 1, 2011, and June 30, 2012. In addition, patients were required
      to have continuous enrollment for 12 months before, and 18 months after, the
      first biologic use (index biologic) during the maintenance period (defined as the
      period following the induction period in which each agent was titrated to its
      recommended maintenance dose per label) and at least 1 prescription filled for
      the index biologic during the 18 months after the maintenance period. Extensive
      above-label use was defined as taking an above-label dose (at least 10% higher
      than indicated in the label) for >= 180 days over a 12-month period following the
      maintenance period. Percentages of patients with extensive above-label use, mean
      number of days of above-label use, and additional costs associated with extensive
      above-label use (abovelabel cost minus on-label cost) were examined. RESULTS: The
      study included 3,310 patients who started treatment with etanercept (n = 1,443),
      adalimumab (n = 1,447), or ustekinumab (n = 420). Extensive above-label use
      occurred in 20.0% of etanercept patients, 2.6% of adalimumab patients, and 14.8%
      of ustekinumab patients. The mean duration of extensive above-label use was
      roughly similar for the 3 biologics (mean days [+/-SD]: 282 [+/-55] for
      etanercept, 279 [+/-57] for adalimumab, and 305 [+/-43] for ustekinumab).
      Additional annual costs per patient because of extensive above-label use were
      $19,458 for etanercept, $18,972 for adalimumab, and $21,045 for ustekinumab.
      Total additional annual costs were $5,623,362 for etanercept, $701,964 for
      adalimumab, and $1,304,790 for ustekinumab. CONCLUSIONS: Psoriasis patients
      treated with etanercept, adalimumab, or ustekinumab had extensive above-label use
      over the 12-month follow-up period, which subsequently led to higher costs.
      DISCLOSURES: Novartis Pharmaceuticals Corporation sponsored this study and the
      resultant publication. BioScience Communications provided medical writing and
      editorial support, which was also funded by Novartis Pharmaceuticals Corporation.
      Feldman was engaged by Novartis Pharmaceuticals as a paid clinical expert and
      scientific advisor for this study. He has received research support and speaking
      and/or consulting fees from AbbVie, Advance Medical, Amgen, Anacor, Astellas,
      Baxter, Boehringer Ingelheim, Caremark, Celgene, Eli Lilly, Galderma,
      GSK/Stiefel, Informa, Janssen, LEO Pharma, Merck, Merz, Mylan, National
      Biological, National Psoriasis Foundation, Pfizer, Qurient, Suncare Research,
      UpToDate, and Valeant; is the founder and majority owner of www.DrScore.com ; and
      is founder and part owner of Causa Research. Zhao, Herrera, Tian, and Li are
      employees of Novartis Pharmaceuticals. Zhou is a paid consultant for Novartis
      Pharmaceuticals and is an employee of KMK Consulting. Study concept and design
      were contributed by Feldman, Zhao, Herrera, and Li. Zhou and Li were responsible
      for data collection. Data were interpreted by Feldman and Zhao, with assistance
      from Zhou, Herrera, Tian, and Li. The manuscript was written primarily by Feldman
      and Zhao, with assistance from Zhou and Li. The manuscript was revised by Feldman
      and Zhao, assisted by Zhou, Herrera, Tian, and Li. Portions of this work were
      presented at the 34th Anniversary Fall Clinical Dermatology Conference in Las
      Vegas, Nevada, October 1-4, 2015.

PMID- 28448779
TI  - Effect of a Pharmacist-Led Program on Improving Outcomes in Patients with Type 2
      Diabetes Mellitus from Northern Cyprus: A Randomized Controlled Trial.
AB  - BACKGROUND: The management of type 2 diabetes mellitus is complex, requiring
      continuous medical care by health care professionals and considerable self-care
      efforts by patients. Pharmacist-led care programs have been shown to help
      patients with diabetes succeed in achieving treatment goals and improving
      outcomes. Pharmacist-led care is a new health care concept in Northern Cyprus.
      OBJECTIVE: To evaluate the effect of a pharmacist-led care program on glycemic
      control, determined by hemoglobin A1c (A1c), and secondarily on blood pressure,
      lipid profile, body mass index (BMI), waist circumference, medication adherence,
      and self-care activities, for patients with type 2 diabetes over a 12-month
      period. METHODS: This was a prospective, randomized controlled study conducted in
      a public hospital's outpatient diabetes clinic, with 152 patients who had been
      diagnosed with type 2 diabetes. Of these, 75 patients were in the intervention
      group, and 77 patients were in the usual care group. The intervention group
      participated in a pharmacist-led care program with a clinical pharmacist who
      provided 5 face-to-face educational sessions over a period of 12 months. The main
      outcome measure was change in A1c, and secondary outcome measures were changes in
      fasting blood glucose, systolic and diastolic blood pressure, lipid values (total
      cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density
      lipoprotein cholesterol [HDL-C], and serum levels of triglycerides [TGs]), BMI,
      waist circumference, self-reported medication adherence (Morisky-Green test), and
      self-care activities. Changes in outcome measures from baseline to the end of the
      study were assessed using the Mann-Whitney U-test and Wilcoxon test. RESULTS: At
      the end of the 12-month study period, the intervention patients showed a greater
      reduction in A1c values than the usual care patients (-0.74% vs. -0.04%; P <
      0.001). Both groups showed significant reductions in fasting blood glucose levels
      between baseline and the end of 12 months; the difference between the groups was
      statistically nonsignificant (P = 0.410). When comparing the intervention and
      usual care groups, there was a significant decrease in systolic (P = 0.01) and
      diastolic blood pressure (P = 0.04) at the end of the trial. No significant
      differences were found between the groups in LDL-C, HDL-C, or TG values; however,
      total cholesterol levels did decrease significantly (P = 0.063, 0.331, 0.896, and
      0.04, respectively). Significant reductions occurred in BMI (P < 0.001) and waist
      circumference (P < 0.001), and improvements were observed in self-reported
      medication adherence and self-care activities in the intervention group.
      CONCLUSIONS: A clinical pharmacist-led care program in a public hospital's
      outpatient diabetes clinic was associated with significant improvements in
      reducing A1c and other secondary outcomes in a 12-month randomized controlled
      study. DISCLOSURES: This study was conducted as a PhD thesis by Korcegez under
      the supervision of Sancar for the clinical pharmacy program at Near East
      University, Health Sciences Institute, Northern Cyprus, and received no external
      funding. The authors have no potential conflicts of interest to report. Study
      concept and design were contributed by Korcegez, with assistance from Sancar and
      Demirkan. Korcegez took the lead in data collection, and data interpretation was
      performed by Korcegez, along with Sancar and Korcegez. The manuscript was written
      and revised by Korcegez, along with Sancar, and with assistance from Demirkan.

PMID- 28448780
TI  - Integration Strategies of Pharmacists in Primary Care-Based Accountable Care
      Organizations: A Report from the Accountable Care Organization Research Network,
      Services, and Education.
AB  - BACKGROUND: The accountable care organization (ACO) is an innovative health care
      delivery model centered on value-based care. ACOs consisting of primary care
      providers are increasingly becoming commonplace in practice; however, medication
      management remains suboptimal. PROGRAM DESCRIPTION: As experts in medication
      management, pharmacists perform direct patient care and assist in the transition
      from one provider to another, which places them in an ideal position to manage
      multiple aspects of patient care. Pharmacist-provided care has been shown to
      reduce drug expenditures, hospital readmissions, length of stay, and emergency
      department visits. Although pharmacists have become key team members of
      interdisciplinary teams within traditional care settings, their role has often
      been overlooked in the primary care-based ACO. In 2015, Nova Southeastern
      University College of Pharmacy founded the Accountable Care Organization Research
      Network, Services, and Education (ACORN SEED), a team of pharmacy practice
      faculty dedicated to using innovative approaches to patient care, while providing
      unique learning experiences for pharmacy students by partnering with ACOs in the
      South Florida region. Five opportunities are presented for pharmacists to improve
      medication use specifically in primary care-based ACOs: medication therapy
      management, annual wellness visits, chronic disease state management, chronic
      care management, and transitions of care. OBSERVATIONS: Several challenges and
      barriers that prevent the full integration of pharmacists into primary care-based
      ACOs include lack of awareness of pharmacist roles in primary care; complex laws
      and regulations surrounding clinical protocols, such as collaborative practice
      agreements; provider status that allows compensation for pharmacist services; and
      limited access to medical records. By understanding and maximizing the role of
      pharmacists, several opportunities exist to better manage the medication-use
      process in value-based care settings. IMPLICATIONS/RECOMMENDATIONS: As more
      organizations realize benefits and overcome barriers to the integration of
      pharmacists into patient care, programs involve pharmacists will become an
      increasingly common approach to improve outcomes and reduce the total cost of
      care and will improve the financial viability of primary care-based ACOs.
      DISCLOSURES: No outside funding supported this research. The authors report no
      conflicts of interest related to this manuscript. Study concept and design were
      contributed by Joseph, Hale, and Eltaki, with assistance from the other authors.
      Prados and Jones took the lead in data collection and data interpretation and
      analysis, with assistance from the other authors. The manuscript was written
      primarily by Joseph and Hale, along with the other authors, and revised primarily
      by Seamon and Gernant, along with the other authors.

PMID- 28448781
TI  - Assessment of Clinical Pharmacy Interventions to Reduce Outpatient Use of High
      Risk Medications in the Elderly.
AB  - BACKGROUND: Use of high-risk medications in the elderly (HRME) and drug-disease
      (Rx-DIS) interactions in the elderly, as defined by the Healthcare Effectiveness
      Data and Information Set (HEDIS) Measures, are significantly associated with
      mortality, hospital admission, and need for emergency care. No published studies
      to date evaluate interventions to reduce the use of HEDIS-defined HRME, although
      many studies have postulated a beneficial effect of such interventions.
      OBJECTIVE: To evaluate the effect of pharmacist interventions on use of HRME and
      Rx-DIS interactions in the outpatient elderly population. METHODS: This
      retrospective cohort study was conducted in a resident-based family medicine
      clinic. Patients aged >= 65 years were prospectively screened for the use of HRME
      and Rx-DIS interactions before their visits with their primary care providers. If
      HRME or Rx-DIS interactions were noted, the clinical pharmacist sent messages to
      the physicians through the electronic medical record, alerting them of the
      findings with suggestions of safer alternative agents, if applicable. The
      recommendation acceptance rate was assessed and then compared with a historical
      control from a similar time frame. The primary outcome was assessed with a chi
      square analysis. Secondary outcomes were assessed with descriptive statistics,
      chi square test, and Fisher's exact test. RESULTS: HRME and/or Rx-DIS
      interactions were changed 25.9% of the time in the pharmacist intervention group
      compared with only 2.0% of the time in the historical control group (P = 0.001).
      The most frequently changed medication classes included skeletal muscle
      relaxants, benzodiazepines, and nonsteroidal anti-inflammatory drugs. Over 85% of
      the medication changes were preserved at the end of the study period. There was
      no difference between groups in the number of patients with HRME or Rx-DIS
      interactions. CONCLUSIONS: Clinical pharmacy interventions result in significant
      reductions in use of HRME and Rx-DIS interactions in the outpatient elderly
      population. Using electronic communication allows pharmacists to provide
      meaningful interventions for numerous patients receiving care in a high-volume
      family medicine clinic setting. DISCLOSURES: There was no funding or sponsorship
      for this study. Rowe reports personal fees from The Medicines Company, outside
      the submitted work. The other authors have nothing to disclose. Study concept and
      design were contributed by Jeter, Chamberlin, and Weddle, with assistance from
      Rowe and Franks. Weddle and Renwick collected the data, and data interpretation
      was performed by Weddle and Rowe, with assistance from Franks. The manuscript was
      written by Weddle and Rowe and revised by Weddle and Franks, assisted by
      Chamberlin. The abstract for the completed study was presented at the American
      College of Clinical Pharmacy Global Conference, San Francisco, California,
      October 2015, and the Southeastern Residency Conference, Athens, Georgia, April
      2015 (platform presentation). The research-in-progress abstract was presented at
      the Tennessee Society of Health System Pharmacists, Nashville, Tennessee,
      February 2015; the American Society of Health System Pharmacists Midyear Clinical
      Meeting, Anaheim, California, December 2014; and the University HealthSystem
      Consortium Pharmacy Council, Anaheim, California, December 2014.

PMID- 28448782
TI  - AMCP Partnership Forum: Driving Value and Outcomes in Oncology.
AB  - : Innovation in cancer treatment has provided a wealth of recently available
      therapeutic agents and a healthy drug pipeline that promises to change the way we
      approach this disease and the lives of those affected in the years to come.
      However, the majority of these new agents, many of which are targeted to specific
      genomic features of various tumors, may challenge the health care system's
      ability to afford cancer care. This innovation drives the need to focus on the
      value of the treatments provided to patients with cancer and on methods to
      optimize the efficiency of the dollars we spend, in addition to the clinical
      value itself. The Academy of Managed Care Pharmacy (AMCP) convened a Partnership
      Forum to address how to improve value and outcomes in cancer care. In this
      multistakeholder forum, several areas were addressed: current methods for
      assessing the value of oncology products, the need for balancing population
      management with precision medicine, and the outlook for value-based contracting
      for oncology medications in managed care settings. Participants recommended ways
      in which stakeholders can work toward solutions in these areas. The forum brought
      together stakeholders from health plans, integrated delivery systems, pharmacy
      benefit managers, clinical practice, biopharmaceutical industry, and laboratory
      companies. Also participating were representatives from trade and professional
      associations. During this 1.5-day forum, participants identified current
      challenges, readiness, and ways to address value and improve outcomes in cancer
      therapy. Some of the challenges identified include choosing a viable (and
      practical) outcome target for value-based contracting in oncology, the
      development and use of value frameworks and clinical pathways, managing cancer
      diagnostics, utilization of alternative payment systems, moving from a large
      evidence base to a small clinical trial base in considering targeted treatments,
      and lack of best practices in value-based payment arrangements. Addressing these
      challenges could lead to improving cancer treatment. DISCLOSURES: The AMCP
      Partnership Forum titled "Driving Value and Outcomes in Oncology" and the
      development of this report were supported by AbbVie, Amgen, Bristol-Myers Squibb,
      Celgene, Foundation Medicine, IntrinsiQ Specialty Solutions, Janssen Oncology and
      Johnson and Johnson Health Systems, Eli Lilly and Company, National
      Pharmaceutical Council, Novartis Pharmaceuticals Corporation, Pharmaceutical
      Research and Manufacturers of America, Sanofi, Takeda Oncology, and Xcenda.

PMID- 28448783
TI  - Effectiveness of a Clinical Pharmacist Medication Therapy Management Program in
      Discontinuation of Drugs to Avoid in the Elderly.
AB  - BACKGROUND: Despite evidence of fall risk associated with some drugs to avoid in
      the elderly (DAEs), many aged patients continue to receive them. OBJECTIVE: To
      assess the effectiveness of a clinical pharmacist medication therapy management
      program (MTM) on discontinuation of prescribed DAEs. METHODS: This was a
      retrospective cohort study conducted at an integrated health care delivery
      system. Kaiser Permanente Colorado beneficiaries aged >=65 years who were MTM
      eligible and targeted for a DAE dispensing between 01/01/2015 and 09/30/2015 were
      included in the observation group. Medicare beneficiaries who were not eligible
      for MTM but had a targeted DAE dispensing during the same time period were
      included in the control group. The percentage of patients with another DAE
      dispensing of the same specified medication (no matter the strength) during the
      100 days following index DAE dispensing was assessed. Univariate and
      multivariable logistic regression analyses were conducted. RESULTS: A total of
      9,059 Medicare beneficiaries were included, with 226 beneficiaries in the MTM
      group and 8,833 beneficiaries in the non-MTM group. Beneficiaries were primarily
      female and white and had a high burden of chronic disease. The percentages of
      patients with another dispensing of the specified DAE were 7.1% (95% CI = 3.7%
      10.4%) for the MTM beneficiaries and 35.3% (95% CI 34.2%-36.2%) for the non-MTM
      beneficiaries (P < 0.001). The OR for the MTM group to have received another
      dispensing of the specified DAE was 0.12 (95% CI = 0.08-0.22) with adjustment for
      potential confounders. CONCLUSIONS: A clinical pharmacist-provided MTM
      intervention was associated with decreased DAE dispensing in Medicare
      beneficiaries. Future studies should evaluate means to further decrease DAE use
      in the aged. DISCLOSURES: This study was funded by the Kaiser Permanente Colorado
      Pharmacy Department. The funder had no role in the study design, collection,
      analysis and interpretation of data, writing of the report, or the decision to
      submit the manuscript for publication. Delate has received grant funding from
      Janssen Pharmaceutical Companies of Johnson & Johnson outside of this study. The
      authors report no other disclosures. Delate supervised the study and had complete
      access to the data and takes responsibility for the data integrity. Study concept
      and design were contributed by Caffiero, Delate, Ehizuelen, and Vogel. Delate
      collected the data, assisted by the other authors, and analysis and
      interpretation of the data were provided by Ehizuelen and Vogel, along with
      Caffiero and Delate. The manuscript was written by Caffiero and Delate, with
      assistance from Ehizuelen and Vogel, and revised by all the authors. Preliminary
      findings from this study were presented at the Mountain States Conference for
      Pharmacy Residents, Fellows, and Preceptors on May 13, 2016, in Salt Lake City,
      Utah.

PMID- 28448784
TI  - A Motivational Interviewing Intervention by Pharmacy Students to Improve
      Medication Adherence.
AB  - BACKGROUND: Diabetes mellitus (DM) patients with comorbid hypertension (HTN) are
      at a higher risk of developing microvascular and macrovascular DM complications.
      Through guideline-driven recommendations, angiotensin-converting enzyme
      inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are highly
      recommended for these patients. Unfortunately, medication adherence to these
      products, though crucial to achieving therapeutic benefit, is frequently
      suboptimal. Motivational interviewing (MI) is a patient-centered collaborative
      communication style that is used to strengthen internal motivation for change
      that may prove effective in enhancing adherence. OBJECTIVE: To examine the effect
      of an MI telephone intervention conducted by pharmacy students in improving
      adherence to ACEIs/ARBs among Medicare Advantage Plan (MAP) patients with both DM
      and HTN. METHODS: A prospective study was conducted among patients enrolled in a
      Texas MAP. Medical claims data were used to identify patients with DM and HTN,
      and pharmacy claims were observed to recognize those who filled either an ACEI or
      an ARB during June 2014. Patients with a 6-month proportion of days covered (PDC)
      < 0.80 in the previous 6 months were determined nonadherent, and 75% of those
      were randomly selected to serve as potential subjects for the intervention, while
      25% were randomly selected to serve as potential subjects for the control group.
      The intervention was a telephone call by a pharmacy student on rotation at the
      health plan, and 5 monthly follow-up calls. Before implementing calls,
      participating students attended a 3-day MI training course, where their
      proficiency for MI skills was evaluated. Refill data during the 6-month
      postintervention were evaluated to examine the intervention effect measured on 3
      outcomes: PDC; PDC >= 0.80 versus < 0.80; and discontinuation versus
      continuation. Multivariate linear and logistic regression models were constructed
      to adjust for any imbalances in baseline characteristics, including age, gender,
      number of other medications, regimen complexity, health low-income subsidy
      status, prescriber specialty, comorbidities, 6-month previous hospitalization,
      baseline 6-month PDC, and Centers for Medicare & Medicaid Services risk score.
      RESULTS: A total of 11 students participated in the intervention implementation.
      Patients receiving calls were randomly selected from those potential subjects for
      the intervention arm until a target of 250 was reached; 500 controls were
      randomly selected from the potential subjects for the control arm. The final
      cohort included in multivariate models consisted of 743 patients. Patients
      completing the initial call and at least 2 follow-ups were less likely to
      discontinue (OR = 0.29; 95% CI = 0.15-0.54; P < 0.001) and more likely to be
      adherent in the linear regression model (beta = 0.0604, P < 0.001) and the
      logistic regression model (OR = 1.53; 95% CI = 1.02-2.28; P = 0.009). Other
      factors significantly associated with better adherence included higher baseline
      PDC and number of medications. Depression status was significantly associated
      with lower adherence. CONCLUSIONS: Patients receiving 2 or more calls had
      significantly better adherence and less discontinuation during the 6 months
      following initial calls compared with those who did not receive calls. This
      finding indicates that an MI-based telephone intervention by pharmacy students
      may be a promising intervention to improve adherence. Future research should
      examine the sustainability of the intervention effect for longer time periods and
      its influence on associated clinical outcomes. DISCLOSURES: This project was
      supported by the Pharmaceutical Research and Manufacturers of America Foundation
      (PhRMA). The content is solely the responsibility of the authors and does not
      necessarily represent the official views of PhRMA. The funding agency was not
      involved in research design, analysis, or reporting results. Funding was obtained
      by Abughosh. Holstad provided a consultation regarding the MI guide and provided
      the MI training. Study concept and design were contributed by Abughosh and
      Fleming, along with Serna, Esse, and Holstad. Serna, Esse, Mann, Holstad, and
      Masilamani collected the data, and data interpretation was performed by Abughosh,
      Wong, and Esse. The manuscript was written by Abughosh, Wong, and Esse and
      revised by Masilamani and Holstad, along with the other authors.

PMID- 28448786
TI  - Microbiological features and clinical impact of the type VI secretion system
      (T6SS) in Acinetobacter baumannii isolates causing bacteremia.
AB  - We investigated the genetic background and microbiological features of T6SS
      positive Acinetobacter baumannii isolates and clinical impact of the T6SS in
      patients with A. baumannii bacteremia. One hundred and 62 A. baumannii isolates
      from patients with bacteremia in 2 tertiary-care hospitals in Korea were included
      in this study. Approximately one-third (51/162, 31.5%) of the A. baumannii
      clinical isolates possessed the hcp gene, and the hcp-positive isolates were
      found in several genotypes in multilocus sequence typing. The expression and
      secretion of Hcp protein varied among the clinical isolates. A. baumannii
      isolates with detectable Hcp secretion (T6SS+) could better outcompete
      Escherichia coli compared with T6SS- isolates, including hcp-negative and
      inactivated hcp-positive isolates. In addition, T6SS+ isolates showed higher
      biofilm-forming activity and better survival in the presence of normal human
      serum than the T6SS- isolates. T6SS+ isolates were more frequently detected in
      patients with catheter-related bloodstream infection, haematopoietic stem cell
      transplant recipients, and patients receiving immunosuppressive agents. However,
      T6SS was not a prognostic factor for mortality. Our results suggest that the T6SS
      of A. baumannii is associated with virulence and contributes to infections in
      immunocompromised patients and those with implanted medical devices.

PMID- 28448785
TI  - A class-II myosin is required for growth, conidiation, cell wall integrity and
      pathogenicity of Magnaporthe oryzae.
AB  - In eukaryotic organisms, myosin proteins are the major ring components that are
      involved in cytokinesis. To date, little is known about the biologic functions of
      myosin proteins in Magnaporthe oryzae. In this study, insertional mutagenesis
      conducted in M. oryzae led to identification of Momyo2, a pathogenicity gene
      predicted to encode a class-II myosin protein homologous to Saccharomyces
      cerevisiae Myo1. According to qRT-PCR, Momyo2 is highly expressed during early
      infectious stage. When this gene was disrupted, the resultant mutant isolates
      were attenuated in virulence on rice and barley. These were likely caused by
      defective mycelial growth and frequent emergence of branch hyphae and septum. The
      Momyo2 mutants were also defective in conidial and appressorial development,
      characterized by abnormal conidia and appressoria. These consequently resulted in
      plant tissue penetration defects that the wild type strain lacked, and mutants
      being less pathogenic. Cytorrhysis assay, CFW staining of appressorium and
      monitoring of protoplast release suggested that appressorial wall was altered,
      presumably affecting the level of turgor pressure within appressorium.
      Furthermore, impairments in conidial germination, glycogen metabolites, tolerance
      to exogenous stresses and scavenging of host-derived reactive oxygen species were
      associated with defects on appressorium mediated penetration, and therefore
      attenuated the virulence of Momyo2 mutants. Taken together, these results suggest
      that Momyo2 plays pleiotropic roles in fungal development, and is required for
      the full pathogenicity of M. oryzae.

PMID- 28448787
TI  - Relationship between HER2 and JAK/STAT-SOCS3 signaling pathway and
      clinicopathological features and prognosis of ovarian cancer.
AB  - OBJECTIVE: The study aims to explore the relationship between expressions of HER2
      and JAK/STAT3-SOCS3 signaling pathway and clinicopathological features and
      prognosis of ovarian cancer (OC). METHODS: A total of 136 OC patients were
      collected. Immunohistochemistry was applied to measure the expressions of STAT3,
      p-STAT3, SOCS3, HER2 and p-HER2 in the tumor tissues and adjacent normal tissues.
      Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the
      mRNA expressions of HER2, SOCS3 and STAT3 and western blotting was applied for
      protein expressions of HER2, p-HER2, SOCS3, STAT3 and p-STAT3 in the tumor
      tissues and adjacent normal tissues. Flow cytometry was used for the cell
      apoptosis in the blank, afatinib (A), ruxolitinib (R) and afatinib + ruxolitinib
      (A + R) groups. Follow-up was performed to explore relationship of HER2, SOCS3,
      and STAT3 expressions with survival time of OC patients. RESULTS: HER2, p-HER2,
      STAT3, and p-STAT3 expressions were higher while SOCS3 expression was lower in
      the tumor tissues. The positive expressions of STAT3, HER2, p-HER2 and p-STAT3
      were lower while the positive expression of SOCS3 was higher in the adjacent
      normal tissues. The expressions of HER2, SOCS3, and p-STAT3 were associated with
      clinical stage and lymph node metastasis (LNM), and STAT3 expression has
      correlation with histological grade and LNM. The mRNA and protein expressions of
      HER2, STAT3 and p-STAT3 in the tumor tissues were higher than those in the
      adjacent normal tissues, but SOCS3 expression was significantly decreased. The
      positive expressions of HER2, p-HER2 and STAT3, the negative expression of SOCS3
      and pathological stages were important risk factors for the prognosis of patients
      with OC. CONCLUSION: Our study showed that the expressions of HER2, STAT3, and
      SOCS3 are associated with the progression of OC, and higher expressions of HER2
      and STAT3 and lower expression of SOCS3 predict poor prognosis of OC.

PMID- 28448788
TI  - Production of biogas from co-digestion of livestock and agricultural residues: A
      case study.
AB  - This study was undertaken to determine the possible changes in the digester yield
      and performance for the anaerobic co-digestion under mesophilic conditions of
      strawberry residues (SRs) together with pig manure (PM). The first part of this
      paper deals with the digestion of SR as a single substrate. For organic loading
      rates (OLRs) of 4.4 (g L-1 d-1) or less, the experimental specific biogas and
      methane productions are 0.588 and 0.231 L g-1, respectively. When higher OLRs
      (5.5 g L-1 d-1) are used the digester fails due to acidification. In the second
      part, the co-digestion of both residues is explored using a wide variety of SR:PM
      ratios and OLRs of 5.5 g L-1 d-1 with good stability. Therefore, it is
      demonstrated that co-digestion allows the improvement of the treatment capacity
      as compared with SR as a single residue. The methane and biogas productions
      increase as the SR:PM ratio increases. It may be concluded that, when a digester
      works with a certain OLR, the performance for co-digestion is always better than
      for single substrates because the presence of PM provides a better stability and
      the presence of SR improves the biogas and methane production.

PMID- 28448789
TI  - Development of pre-implantation porcine blastocysts cultured within alginate
      hydrogel systems either supplemented with secreted phosphoprotein 1 or conjugated
      with Arg-Gly-Asp Peptide.
AB  - Although deficiencies in porcine blastocyst elongation play a significant role in
      early embryonic mortality and establishment of within-litter developmental
      variation, the exact mechanisms of elongation are poorly understood. Secreted
      phosphoprotein 1 (SPP1) is increased within the uterine milieu during early
      porcine pregnancy and contains an Arg-Gly-Asp (RGD) peptide sequence that binds
      to cell surface integrins on the uterine endometrium and trophectoderm, promoting
      cell adhesion and migration. The aim of the present study was to evaluate the
      development of preimplantation porcine blastocysts encapsulated and cultured
      within alginate hydrogels either supplemented with SPP1 or conjugated with RGD.
      Blastocysts encapsulated within alginate hydrogels supplemented with SPP1 or
      conjugated with RGD had increased survival compared with non-encapsulated control
      blastocysts. In addition, the percentage of blastocysts encapsulated within RGD
      hydrogels that underwent morphological changes was greater than that of
      blastocysts encapsulated within standard alginate hydrogels or SPP1-supplemented
      hydrogels. Finally, only blastocysts encapsulated within RGD hydrogels had both
      increased expression of steroidogenic and immune responsiveness transcripts and
      increased 17beta-oestradiol production, consistent with blastocysts undergoing
      elongation in vivo. These results illustrate the importance of the integrin
      binding RGD peptide sequence for stimulating the initiation of blastocyst
      elongation.

PMID- 28448790
TI  - Drinking and driving behavior at stop signs and red lights.
AB  - Alcohol is one of the principal risk factors for motor vehicle crashes. One
      factor that contributes to vehicle crashes is noncompliance with stop signs and
      red lights. The present experiment investigated the effects of alcohol and
      drinking patterns on driving behavior at stop signs and red lights. 28
      participants participated in drinking and simulated driving sessions during which
      they received a moderate dose of alcohol (0.08% BAC) or a placebo. Simulated
      driving tasks measured participants' driving performance at stop signs and red
      lights in response to each dose. Results suggested that alcohol impaired the
      driver control of speed and direction and prolonged their simple and complex
      reaction time, which were exhibited by impaired speed and lateral control, longer
      reaction time when the lights turned yellow, and lower deceleration towards stop
      signs and red lights. Visual degradation may also occur under alcohol intake. It
      was also suggested that alcohol impaired non-binge drinkers more severely. To be
      specific, higher acceleration was observed in impaired non-binge drinkers.

PMID- 28448791
TI  - Self-grounding visual, auditory and olfactory autobiographical memories.
AB  - Given that autobiographical memory provides a cognitive foundation for the self,
      we investigated the relative importance of visual, auditory and olfactory
      autobiographical memories for the self. Thirty subjects, with a mean age of
      35.4years, participated in a study involving a three*three within-subject design
      containing nine different types of autobiographical memory cues: pictures, sounds
      and odors presented with neutral, positive and negative valences. It was shown
      that visual compared to auditory and olfactory autobiographical memories involved
      higher cognitive and emotional constituents for the self. Furthermore, there was
      a trend showing positive autobiographical memories to increase their proportion
      to both cognitive and emotional components of the self, from olfactory to
      auditory to visually cued autobiographical memories; but, yielding a reverse
      trend for negative autobiographical memories. Finally, and independently of
      modality, positive affective states were shown to be more involved in
      autobiographical memory than negative ones.

PMID- 28448792
TI  - Imagining possible selves across time: Characteristics of self-images and
      episodic thoughts.
AB  - Thinking about our possible selves can entail thinking about self-related
      imagined future events. When remembering and imagining, individuals can use both
      1st person (field) and 3rd person (observer) perspectives. There is currently a
      paucity of research examining the visual perspectives of episodic future thoughts
      that represent possible selves. We hypothesised that temporally distant self
      images would elicit more observer perspectives in episodic thoughts than
      temporally near self-images and current self-images. Utilising a repeated
      measures design, sixty-eight undergraduate students completed IAM, I Will Be near
      and I Will Be far conditions (Rathbone, Conway, & Moulin, 2011) to generate self
      images and their related episodic thoughts. It was found that episodic qualities
      were reliably affected by different self-images. Specifically, observer
      perspective predilections increased with future temporal distance. Findings are
      discussed in relation to self-continuity with recommended practical applications
      of visual perspective utilisation for wellbeing.

PMID- 28448793
TI  - To Circuitry and Beyond.

PMID- 28448794
TI  - Principles of Systems Biology, No. 16.
AB  - This month: how T cells signal in binary (Vale), advances in interaction mapping
      (Greenleaf/Sabatini/Ahroni/Bodenmiller), single-cell RNA-seq
      (Suva/Ramanathan/Marioni), and more (Hilvert/Wong/Chisholm).

PMID- 28448795
TI  - What Is the Role of Circuit Design in the Advancement of Synthetic Biology? Part
      1.
AB  - Enabling real-world applications and therapeutics.

PMID- 28448796
TI  - Reconciling Epigenetic Memory and Transcriptional Responsiveness.
AB  - The molecular basis of cellular memory is important but poorly understood. Using
      estimates of histone dynamics, Martin Howard and colleagues construct a
      mathematical model that helps to explain both the stability and flexibility of
      Polycomb-mediated gene regulation in cellular memory.

PMID- 28448797
TI  - The Single-Cell Yin and Yang of Live Imaging and Transcriptomics.
AB  - A new approach to monitoring both signaling over time and a global gene
      expression profile from the same cell establishes a functional role for NF-kappaB
      dynamics in transcription.

PMID- 28448798
TI  - Chemodiversity of two closely related tetraploid Centaurium species and their
      hexaploid hybrid: Metabolomic search for high-resolution taxonomic classifiers.
AB  - Species within the genus Centaurium readily hybridize and polyploid complexes are
      often seen in natural populations. We describe phytochemical profiles of newly
      discovered allohexaploid hybrid, here named Centaurium pannonicum, and its
      parental tetraploid species C. erythraea and rare C. littorale ssp. compressum.
      Our aim was to examine chemodiversity of these taxa in the area of Vojvodina
      (North Serbia) and to perform metabolomics search for chemical classifiers which
      would provide high resolution discrimination of parental and hybrid individuals.
      In sum, UHPLC-MS/MS Orbitrap metabolomics fingerprinting revealed seventy
      compounds in methanol extracts. Despite the lack of qualitative chemical novelty
      in hybrid plants, UHPLC-qqqMS targeted metabolomics approach, aimed at three
      secoiridoid compounds and seventeen phenolics, pointed to considerable
      differences in quantitative composition of these dominant compounds among the
      plant taxa studied. In addition to the difference in the ploidy levels, the
      hybrid taxon was well distinguished from both parental species based on
      metabolite profiles, and, for most individuals, positioned intermediately to the
      parental taxa in both PCA and hierarchical clustering. After optimizing and
      comparing several statistical learning methods, it was possible to narrow the
      number of taxonomic classifiers to five (three xanthones, one secoiridoid
      glycoside, and one phenolic acid), while increasing the differentiation
      resolution. The presented metabolomics approach will certainly, along with
      morphometrics and molecular genetics studies, have high impact on further
      elucidation of complex relationships among taxa within the genus Centaurium.

PMID- 28448799
TI  - Isolation of antioxidant phenolics from Schinopsis brasiliensis based on a
      preliminary LC-MS profiling.
AB  - The phenolic content of the ethanol extract of the stem bark of the Brazilian
      plant Schinopsis brasiliensis Engl. (Anacardiaceae) has been evaluated together
      with the antioxidant activity. The good antioxidant activity exhibited in the
      Trolox Equivalent Antioxidant Capacity (TEAC) assay (TEAC value = 3.04 mg/mL)
      encouraged us to investigate its constituents. An analytical approach based on LC
      ESIMSn was applied to rapidly obtain a metabolite profile of the ethanol extract
      of the stem bark of S. brasiliensis. Sixteen phenolic compounds, among which five
      galloyl derivatives, never reported before, have been isolated and their
      structures have been unambiguously elucidated by extensive spectroscopic methods,
      including 1D (1H, 13C, TOCSY) and 2D (DQF-COSY, HMBC, and HSQC) NMR experiments.
      Moreover, the antioxidant activity of all the isolated compounds was evaluated,
      along with the cytotoxicity against the cancer cell lines A549 (human alveolar
      basal carcinoma) and Hela (human epitheloid cervix carcinoma). The previously
      undescribed compounds exhibited a high free-radical-scavenging activity, in the
      range of 1.10-1.86 mM. None of the tested compounds, in a range of concentrations
      between 12.5 and 100 MUM, caused a significant reduction of the cell number.

PMID- 28448800
TI  - Assessment of bilingual children: What if testing both languages is not possible?
AB  - : Language delays of bilingual children can arise from language impairment (LI)
      but also from insufficient exposure to the target language. A reliable diagnosis
      of LI in bilingual children is therefore ideally based on the evaluation of both
      languages, as LI affects each language that is learned. However, due to the
      multitude of language combinations that are encountered in clinical practice,
      this is often not feasible. Bilingual norm-referencing may offer a solution, but
      the heterogeneity within the bilingual population makes it difficult to determine
      appropriate standards for every child. The present study examined an alternative
      approach to assessing both languages or using bilingual norm-referencing, aiming
      to assemble instruments that reduce bias against bilingual children. We used a
      four-group design, including monolingual and bilingual children with and without
      LI (N=132), to first investigate the effects of LI and bilingualism on risks
      associated with a child's early language development and the prevalence of
      language problems in the family, as reported by parents. Second, we evaluated the
      diagnostic validity of these two indices, and, in addition, combined these with
      two unbiased language measures which we previously examined in isolation: a quasi
      universal nonword repetition task and a narrative task. Results showed that the
      index of Early Language Development was a strong predictor of LI. In combination
      with the two direct language measures, it excellently identified the presence or
      absence of LI in and across monolingual and bilingual learning contexts. LEARNING
      OUTCOMES: As a result of this study, the reader will learn about an alternative
      approach to testing a bilingual child in both languages. The reader will
      recognize the importance of using unbiased measures for the identification of LI
      in a bilingual context, and, in addition, will appreciate the value of combining
      parental report with direct language measures.

PMID- 28448801
TI  - The placental factor in spontaneous preterm birth in twin vs. singleton
      pregnancies.
AB  - OBJECTIVE: The association between infection and inflammatory response in
      singleton preterm birth (PTB) is well established, yet, less is known about PTB
      in twins. We aimed to compare the placental component and pregnancy outcome in
      pregnancies complicated with PTB of singletons vs. twin deliveries. We
      hypothesized that due to different underlying mechanisms, placental inflammatory
      lesions will be more prevalent in placentas derived from singleton pregnancies
      than twins. STUDY DESIGN: Labor characteristics, neonatal outcome and placental
      histopathology reports of spontaneous PTB at 24-336/7 weeks, from 1/2008-12/2015,
      were reviewed. RESULTS: were compared between dichorionic-diamniotic twin
      deliveries (twins group) and singleton deliveries (singleton group) matched for
      gestational age. Excluded from the study medically indicated deliveries, due to
      preeclampsia or fetal growth restriction, and monochorionic twins. Placental
      lesions were classified to maternal vascular supply lesions, fetal vascular
      supply lesions, and maternal (MIR) and fetal (FIR) inflammatory responses.
      Composite neonatal outcome was defined as one or more of early complications:
      respiratory distress, necrotizing enterocolitis, sepsis, blood transfusion,
      ventilation, seizures, intra-ventricular hemorrhage, hypoglycemia, phototherapy,
      or death. RESULTS: The twins group (n=72) was characterized by higher maternal
      BMI (p=0.009), and higher rates of assisted reproductive techniques (56.2% vs.
      17.8%, p<0.001) and cesarean deliveries (75.3% vs. 32.8%, p<0.001) as compared to
      the singleton group (n=72). Placentas from the singleton group were characterized
      by higher rate of MIR, 58.9% vs. 19.2%, (p<0.001), FIR, 31.5% vs. 3.4%,
      (p<0.001), retro-placental hemorrhage, 26% vs. 8.9% (p<0.001), and vascular
      lesions related to maternal malperfusion, 28.8% vs. 9.6%, (p<0.001), as compared
      to placentas from the twins group. Higher rate of neonatal sepsis was observed in
      the singleton group as compared to the twins group, 24.7% vs. 4.1%, p<0.001,
      respectively. By logistic regression analyses retro-placental hemorrhage,
      placental maternal vascular malperfusion lesions, MIR, FIR and neonatal sepsis
      were found to be independently associated with singleton PTB: aOR 3.4, 95% CI 2.1
      6.9, p<0.001, aOR=3.1, 95% CI 1.8-7.2, p<0.001, aOR=2.9, 95% CI 1.4-7.8, p<0.001,
      aOR=4.9, 95% CI 2.3-6.9, p<0.001, and aOR=4.8, 95% CI 2.3-6.7, p<0.001
      respectively. CONCLUSION: Placentas from singleton PTBs are characterized by
      higher rate of inflammatory and malperfusion lesions. The lack of these findings
      in twins PTBs suggests different factors that participate in the development of
      preterm birth in twins, such as over-distension of the uterus and up regulation
      of oxytocin receptors.

PMID- 28448803
TI  - Emotion regulation as a moderator between anxiety symptoms and insomnia symptom
      severity.
AB  - Insomnia is a common concern with many associated negative consequences. Previous
      research has established bivariate relationships between anxiety symptoms,
      emotion regulation, and insomnia symptom severity; however, limited research has
      examined how the interaction between emotion regulation and anxiety symptoms may
      be associated with insomnia symptom severity. A sample of 468 undergraduate
      participants and a subsample of 136 participants meeting a self-reported cutoff
      score for insomnia, completed questionnaires assessing anxiety, insomnia symptom
      severity, and emotion regulation difficulties. Among the general sample of all
      participants, the interaction between anxiety symptoms and both overall emotion
      regulation difficulties and limited access to emotion regulation strategies were
      associated with insomnia symptom severity. However, among the insomnia subsample,
      emotion regulation moderated this relationship, such that insomnia symptom
      severity increased as anxiety symptoms increased among those with high emotion
      regulation difficulties, but were unaffected by changes in anxiety symptoms among
      those with low emotion regulation difficulties. These findings suggest that
      maladaptive emotion regulation may be necessary for anxiety symptoms to have a
      negative influence on sleep difficulties, meaning that during treatment, it may
      be important to address both an individual's anxiety symptoms and emotion
      regulation difficulties, particularly among those with clinical levels of
      insomnia.

PMID- 28448802
TI  - DDK Promotes Tumor Chemoresistance and Survival via Multiple Pathways.
AB  - DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA
      replication at individual origins and is composed of CDC7 kinase and its
      regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor
      cell lines and primary tumors, and this is correlated with poor prognosis.
      Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a
      largely unknown mechanism. Firstly, to understand why DDK is often overexpressed
      in tumors, we identified gene expression signatures that correlate with DDK high-
      and DDK low-expressing lung adenocarcinomas. We found that increased DDK
      expression is highly correlated with inactivation of RB1-E2F and p53 tumor
      suppressor pathways. Both CDC7 and DBF4 promoters bind E2F, suggesting that
      increased E2F activity in RB1 mutant cancers promotes increased DDK expression.
      Surprisingly, increased DDK expression levels are also correlated with both
      increased chemoresistance and genome-wide mutation frequencies. Our data further
      suggest that high DDK levels directly promote elevated mutation frequencies.
      Secondly, we performed an RNAi screen to investigate how DDK inhibition causes
      apoptosis of tumor cells. We identified 23 kinases and phosphatases required for
      apoptosis when DDK is inhibited. These hits include checkpoint genes, G2/M cell
      cycle regulators, and known tumor suppressors leading to the hypothesis that
      inhibiting mitotic progression can protect against DDKi-induced apoptosis.
      Characterization of one novel hit, the LATS2 tumor suppressor, suggests that it
      promotes apoptosis independently of the upstream MST1/2 kinases in the Hippo
      signaling pathway.

PMID- 28448804
TI  - The associations between childhood trauma, neuroticism and comorbid obsessive
      compulsive symptoms in patients with psychotic disorders.
AB  - Various studies reported remarkably high prevalence rates of obsessive-compulsive
      symptoms (OCS) in patients with a psychotic disorder. Little is known about the
      pathogenesis of this co-occurrence. The current study aimed to investigate the
      contribution of shared underlying risk factors, such as childhood trauma and
      neuroticism, to the onset and course of OCS in patients with psychosis. Data were
      retrieved from 161 patients with psychosis included in the 'Genetic Risk and
      Outcome in Psychosis' project. Patients completed measures of OCS and psychotic
      symptoms at study entrance and three years later. Additionally, childhood
      maltreatment and neuroticism were assessed. Between-group comparisons revealed
      increased neuroticism and positive symptoms in patients who reported comorbid OCS
      compared to OCS-free patients. Subsequent mediation analyses suggested a small
      effect of childhood abuse on comorbid OCS severity at baseline, which was
      mediated by positive symptom severity. Additionally, results showed a mediating
      effect of neuroticism as well as a moderating effect of positive symptoms on the
      course of OCS severity over time. OCS severity in patients with psychosis might
      thus be associated with common vulnerability factors, such as childhood abuse and
      neuroticism. Furthermore, the severity of positive symptoms might be associated
      with more severe or persistent comorbid OCS.

PMID- 28448805
TI  - The associations between quality of life and clinical symptoms in individuals
      with an at-risk mental state and first-episode psychosis.
AB  - Quality of life (QOL) is strongly associated with severity of clinical symptoms
      and is often compromised in patients with chronic or first-episode psychosis
      (FEP). However, it remains unclear whether baseline QOL in individuals with an at
      risk mental state (ARMS) for psychosis is higher or lower than that in patients
      with FEP, or what specific clinical symptoms relate to a decreased QOL in
      individuals with ARMS and FEP. The World Health Organization's WHOQOL-BREF, an
      instrument assessing QOL, was administered to 104 individuals with ARMS and 53
      with FEP. Clinical symptoms were assessed by the Positive and Negative Syndrome
      Scale and the Beck Depression Inventory-II. We compared the four domain scores of
      the WHOQOL-BREF between the two groups, and calculated Pearson correlations
      between each WHOQOL-BREF domain score and the clinical symptoms and compared
      these correlations between the groups. We observed significant correlations
      between poor QOL and severity of depressive symptoms in both the FEP and ARMS
      group. No between-group differences were found in any correlation coefficients
      between WHOQOL-BREF domains and clinical symptoms. Thus, depressive symptoms
      should be investigated as a key factor relating to poor QOL in both individuals
      with ARMS and those with FEP.

PMID- 28448806
TI  - Exostosin 1 is expressed in human odontoblasts.
AB  - OBJECTIVE: Dental pulp is soft connective tissue maintaining the vitality of the
      tooth, while odontoblasts form the dentin. Our earlier DNA microarray analysis
      revealed expression of putative tumour suppressor exostosin 1 (EXT-1) in
      odontoblasts. EXT-1 is essential for heparan sulphate synthesis, which may play a
      role in the dentin mineralization. Since the absence of the functional EXT-1
      causes bone tumours, expression in odontoblasts is interesting. Our aim was to
      analyse further the EXT-1 expression in human tooth. DESIGNS: DNA microarray and
      PCR techniques were used to study the EXT-1 expression in mature native human
      odontoblasts and pulp tissue as well as in newly-differentiated cultured
      odontoblast-like cells. Immunohistochemistry was performed to study EXT-1 protein
      in mature human teeth, teeth with incomplete root and developing teeth. RESULTS:
      Markedly higher EXT-1 was observed in mature odontoblasts than in pulp at mRNA
      level with DNA microarray and PCR techniques. Immunohistochemistry of mature
      tooth revealed EXT-1 both in odontoblasts and the predentin but not in the
      dentin. EXT-1 was also observed in the odontoblasts of incomplete root, but the
      localization of the staining was different. In developing foetal tooth, staining
      was detected in ameloblasts and the basal lamina. CONCLUSIONS: The detection of
      EXT-1 in both mature and newly-differentiated cells indicates a role in the
      odontoblast function, and EXT-1 staining in the predentin indicates a function in
      the dentin formation. Detection of EXT-1 in developing teeth indicates a role in
      tooth development.

PMID- 28448807
TI  - Alternative sweeteners influence the biomass of oral biofilm.
AB  - OBJECTIVE: Compact-structured oral biofilm accumulates acids that upon prolonged
      exposure to tooth surface, causes demineralisation of enamel. This study aimed to
      assess the effect of alternative sweeteners Equal Stevia(r), Tropicana Slim(r),
      Pal Sweet(r) and xylitol on the matrix-forming activity of plaque biofilm at both
      the early and established stages of formation. METHODS: Saliva-coated glass beads
      (sGB) were used as substratum for the adhesion of a mixed-bacterial suspension of
      Streptococcus mutans, Streptococcus sanguinis and Streptococcus mitis. Biofilms
      formed on sGB at 3h and 24h represented the early and established-plaque models.
      The biofilms were exposed to three doses of the sweeteners (10%), introduced at
      three intervals to simulate the exposure of dental plaque to sugar during three
      consecutive food intakes. The treated sGB were (i) examined under the SEM and
      (ii) collected for turbidity reading. The absorbance indicated the amount of
      plaque mass produced. Analysis was performed comparative to sucrose as control.
      RESULTS: Higher rate of bacterial adherence was determined during the early
      compared to established phases of formation. Comparative to the sweeteners,
      sucrose showed a 40% increase in bacterial adherence and produced 70% more plaque
      mass. Bacterial counts and SEM micrographs exhibited absence of matrix in all the
      sweetener-treated biofilms at the early phase of formation. At the established
      phase, presence of matrix was detected but at significantly lower degree compared
      to sucrose (p<0.05). CONCLUSION: Alternatives sweeteners promoted the formation
      of oral biofilm with lighter mass and lower bacterial adherence. Hence,
      suggesting alternative sweeteners as potential antiplaque agents.

PMID- 28448808
TI  - Identifying conflict potential in a coastal and marine environment using
      participatory mapping.
AB  - Planning for coastal and marine environments is often characterized by conflict
      over current and proposed uses. Marine spatial planning has been proposed as a
      way forward, however, social data are often missing impeding decision-making.
      Participatory mapping, a technique useful for providing social data and predict
      conflict potential, is being used in an increasing number of terrestrial
      applications to inform planning, but has been little used in the marine realm.
      This study collected social data for an extensive coastline in northwestern
      Australia via 167 in-depth face-to-face interviews including participant mapping
      of place values. From the transcribed interviews and digitized maps, we
      inductively identified 17 values, with biodiversity, the physical landscape, and
      Aboriginal culture being most valued. To spatially identify conflict potential,
      values were classified in matrices as consumptive or non-consumptive with the
      former assumed to be less compatible with other values. Pairwise comparisons of
      value compatibilities informed a spatial GIS determination of conflict potential.
      The results were overlaid with the boundaries of nine marine protected areas in
      the region to illustrate the application of this method for marine spatial
      planning. The three near shore marine protected areas had at least one third of
      their area exhibiting conflict potential. Participatory mapping accompanied by
      conflict potential mapping provides important insights for spatial planning in
      these often-highly contested marine environments.

PMID- 28448809
TI  - Recent land-use and land-cover changes and its driving factors in a fire-prone
      area of southwestern Turkey.
AB  - During the last decades, contrasted trends in forest fires among countries around
      the Mediterranean basin have been observed. In the northern/western countries,
      Land Use-Land Cover (LULC) changes led to more hazardous landscapes, with
      consequent increases in fires. This contrasted with fire trends in
      southern/eastern countries. The recent incidence of large fires in some of the
      latter prompted the question of whether they are now following the path of their
      neighbors decades earlier. In this study, we investigated recent LULC changes in
      southwestern Turkey, focusing on those that could affect fire, and the factors
      driving them. To this end, LULC maps at different time steps (1975, 1990, 2000
      and 2010) were obtained from Landsat images, together with relevant socioeconomic
      data. Generalized linear mixed models (GLMMs) were applied to assess the effects
      of socioeconomic and geophysical factors on the dominant LULC changes over time.
      Over the whole period studied, the most important LULC changes were deforestation
      followed by afforestation. Deforestation was positively related to high livestock
      density and proximity to villages and increased forest interfaces with other LULC
      types. We found no evidence that LULC changes were making the landscape more
      hazardous as there was a net decrease in fuels biomass and the landscape became
      more fragmented over time. However, despite the area being heavily used and
      relatively fragmented, large fires can occur driven by severe weather.

PMID- 28448810
TI  - Associations between blood BTEXS concentrations and hematologic parameters among
      adult residents of the U.S. Gulf States.
AB  - BACKGROUND: Studies of workers exposed to benzene at average air concentrations
      below one part per million suggest that benzene, a known hematotoxin, causes
      hematopoietic damage even at low exposure levels. However, evidence of such
      effects outside of occupational settings and for other volatile organic compounds
      (VOCs) is limited. OBJECTIVE: To investigate associations between ambient
      exposures to five VOCs, including benzene, and hematologic parameters among adult
      residents of the U.S. Gulf Coast. MATERIALS AND METHODS: Blood concentrations of
      selected VOCs were measured in a sample of adult participants in the Gulf Long
      term Follow-up Study (GuLF STUDY) during 2012 and 2013. Complete blood counts
      with differentials were also performed on a subset of participants (n=406). We
      used these data together with detailed questionnaire data to estimate adjusted
      associations between blood BTEXS (benzene, toluene, ethylbenzene, o-xylene, m/p
      xylene, and styrene) concentrations and hematologic parameters using generalized
      linear models. RESULTS: We observed inverse associations between blood benzene
      concentrations and hemoglobin concentration and mean corpuscular hemoglobin
      concentration, and a positive association with red cell distribution width among
      tobacco smoke-unexposed participants (n=146). Among tobacco smoke-exposed
      participants (n=247), we observed positive associations between blood VOC
      concentrations and several hematologic parameters, including increased white
      blood cell and platelet counts, suggestive of hematopoietic stimulation typically
      associated with tobacco smoke exposure. Most associations were stronger for
      benzene than for the other VOCs. CONCLUSIONS: Our results suggest that ambient
      exposure to BTEXS, particularly benzene, may be associated with hematologic
      effects, including decreased hemoglobin concentration, mean corpuscular
      hemoglobin concentration, and increased red cell distribution width.

PMID- 28448811
TI  - Effect of addition of sewage sludge and coal sludge on bioavailability of
      selected metals in the waste from the zinc and lead industry.
AB  - This study evaluated the content of bioavailable forms of selected heavy metals
      present in the waste from Zn and Pb processing that can potentially have an
      effect on the observed difficulties in reclamation of landfills with this waste.
      The particular focus of the study was on iron because its potential excess or
      deficiency may be one of the causes of the failure in biological reclamation. The
      study confirmed that despite high content of total iron in waste (mean value of
      200.975gkg-1), this metal is present in the forms not available to plants (mean:
      0.00009gkg-1). The study attempted to increase its potential bioavailability
      through preparation of the mixtures of this waste with additions in the form of
      sewage sludge and coal sludge in different proportions. Combination of waste with
      10% of coal sludge and sewage sludge using the contents of 10%, 20% and 30%
      increased the amounts of bioavailable iron forms to the level defined as
      sufficient for adequate plant growth. The Lepidum sativum test was used to
      evaluate phytotoxicity of waste and the mixtures prepared based on this waste.
      The results did not show unambiguously that the presence of heavy metals in the
      waste had a negative effect on the growth of test plant roots.

PMID- 28448812
TI  - Effect of exposure to p,p'-DDE during the first half of pregnancy in the maternal
      thyroid profile of female residents in a Mexican floriculture area.
AB  - BACKGROUND: Dichlorodiphenyldichloroethene (p,p'-DDE), the main metabolite of
      dichlorodiphenyltrichloroethane (DDT), has been associated with changes in human
      thyroid hormone levels. Maternal thyroid hormones are essential for adequate
      fetal neurodevelopment during the first half of pregnancy. OBJECTIVE: To evaluate
      the association between maternal p,p'-DDE concentration and the maternal thyroid
      profile during the first half of pregnancy. MATERIALS AND METHODS: We analyzed
      the information of 430 pregnant women from a Mexican floriculture area, with a
      gestational age <=16 weeks. By questionnaire, we obtained sociodemographic,
      reproductive, and life-style, information. Serum concentrations of thyroid
      stimulating hormone (TSH), and total and free T3 and T4 were determined by means
      of Enzyme-Linked ImmunoSorbent Assay (ELISA). p,p'-DDE was analyzed by Gas
      Chromatography. The association between p,p'-DDE and thyroid profile was assessed
      through linear and logistic regression models. RESULTS: Thirty eight percent of
      women had p,p'-DDE levels below the Limit of Detection and 12.3% below the Limit
      of Quantification. Within the quantifiable range, median was 53.03ng/g. TSH >2.5
      mIU/L was present in 9.3% of women; 47.7% had isolated hypothyroxinemia; 3.5% had
      subclinical hypothyroidism, and 5.8% had overt hypothyroidism. We observed a
      significant positive association between quantifiable p,p'-DDE and total T3 serum
      levels in comparison with those with concentrations below the Limit of Detection
      (beta=0.19; 95% CI=0.06, 0.34). There were no significant associations with other
      hormones of the thyroid profile or with clinical diagnosis. CONCLUSIONS: Our
      findings suggest that p,p'-DDE exposure, even at low concentrations, could
      disrupt thyroid homeostasis during pregnancy.

PMID- 28448813
TI  - Adverse childhood experiences, mental health, and excessive alcohol use:
      Examination of race/ethnicity and sex differences.
AB  - Responses from N=60,598 interviews from the 2010 Behavioral Risk Factor
      Surveillance System (the 10 states and the District of Columbia that included the
      optional Adverse Childhood Experience (ACE) module) were used to test whether
      associations between childhood adversity and adult mental health and alcohol
      behaviors vary by race/ethnicity and sex. ACE items were categorized into two
      types - household challenges and child abuse. Outcomes were current depression,
      diagnosed depression, heavy drinking and binge drinking. Logistic regression
      models found ACEs significantly associated with depression and excessive alcohol
      use, but sex did not moderate any relationships. Race/ethnicity moderated the
      relationship between ACEs and heavy drinking. In stratified analyses, compared to
      those not exposed to ACEs, non-Hispanic blacks who experienced either type of ACE
      were about 3 times as likely to drink heavily; Non-Hispanic whites who
      experienced child abuse or both ACE types were 1.5-2 times as likely to drink
      heavily; and Hispanics who experienced household challenges or both ACE types
      were 1.2 and 11 times as likely to report heavy drinking. ACEs impact depression
      and excessive alcohol use similarly across men and women. With the exception of
      heavy drinking, ACEs appear to have the same association with excessive alcohol
      use across race/ethnicity. It may be prudent to further investigate why the
      relationship between ACEs and heavy drinking may differ by race/ethnicity such
      that prevention strategies can be developed or refined to effectively address the
      needs of all sub-groups.

PMID- 28448814
TI  - Which maltreated children are at greatest risk of aggressive and criminal
      behavior? An examination of maltreatment dimensions and cumulative risk.
AB  - This paper explores the well-documented relationship between child maltreatment
      and aggressive and criminal behavior, specifically examining several dimensions
      of maltreatment and cumulative child and family risk. Using data from the
      provincially representative Ontario Incidence Study of Reported Child Abuse and
      Neglect (OIS-2013), this paper utilizes a developmental lens to examine whether
      maltreatment dimensions and cumulative risk can differentiate maltreated young
      people who exhibit aggressive and criminal behaviors and those who do not. A
      total unweighted sample of 1837 substantiated maltreatment investigations was
      examined in this analysis using chi-square, t-test, and logistic regression. The
      findings indicate that 13% of maltreated children and youth served by the Ontario
      child welfare system exhibited aggression and 6% of maltreated adolescents were
      involved in the youth justice system. Aggressive children and youth were more
      likely to experience severe and co-occurring forms of maltreatment and to
      experience higher levels of cumulative child risk. In adolescence, youth
      exhibiting aggressive and/or criminal behavior commonly were investigated because
      of neglect, specifically because their caregivers were no longer willing or able
      to remain in a caregiving role. Implications for child welfare policy and
      practice are discussed.

PMID- 28448815
TI  - Spanking and subsequent behavioral problems in toddlers: A propensity score
      matched, prospective study in Japan.
AB  - Harsh or frequent spanking in early childhood is an established risk factor for
      later childhood behavioral problems as well as mental disorder in adulthood in
      Western societies. However, few studies have been conducted in Asian populations,
      where corporal punishment is relatively accepted. Moreover, the impacts of
      occasional spanking on subsequent behavioral problems remain uncertain. This
      study sought to investigate prospectively the association between the frequency
      of spanking of toddlers and later behavioral problems in Japanese children using
      national birth cohort data. We used data from the Longitudinal Survey of Newborns
      in the 21st Century, a population-based birth cohort data set collected by the
      Japanese Ministry of Health, Labour, and Welfare (N=29,182). Frequency of
      spanking ("never", "sometimes" and "always") and child behavioral problems were
      assessed via a caregiver questionnaire when the child was 3.5 years old and again
      at 5.5 years. Propensity score matching was used to examine the association
      between frequency of spanking and child behavioral problems, adjusting for
      parental socioeconomic status, child temperament and parenting behaviors.
      Compared to children who were never spanked, occasional spanking ("sometimes")
      showed a higher number of behavioral problems (on a 6-point scale) (coefficient:
      0.11, 95% CI: 0.07-0.15), and frequent spanking ("always") showed an even larger
      number of behavioral problems compared with "sometimes" (coefficient: 0.08, 95%
      CI:0.01-0.16). Spanking of any self-reported frequency was associated with an
      increased risk for later behavioral problems in children.

PMID- 28448816
TI  - Protective effect of artemisinin on chronic alcohol induced-liver damage in mice.
AB  - The liver disease related to chronic alcohol consumption is one of the leading
      causes of death for alcoholics. The efficient drug to ameliorate the alcoholic
      liver injury was needed urgently. The present study was performed to investigate
      whether artemisinin possessed the protective effect against chronic alcohol
      consumption. 50 male Kunming mice were divided into 5 groups: control group (C):
      10ml/kg saline+10ml/kg saline, alcohol group (A): 10ml/kg 56%(v/v)
      alcohol+10ml/kg saline, low dose group of artemisinin (L): 10ml/kg 56%(v/v)
      alcohol+30mg/kg/day artemisinin, medium dose group of artemisinin (M): 10ml/kg
      56%(v/v) alcohol+60mg/kg/day artemisinin, high dose group of artemisinin (H):
      10ml/kg 56%(v/v) alcohol+120mg/kg/day artemisinin. Drugs were given orally every
      day. The general state of mice was observed and the levels of serum activities of
      AST and ALT were detected after treatment with drugs for 30days. Besides, the
      liver weight index was calculated and histopathological analysis was performed.
      We successfully demonstrated that treatment with high dose of artemisinin
      significantly decreased the elevated levels of AST (p<0.05) and ALT (p<0.01) in
      plasma, as well as the liver weight index (p<0.01). The loss of body weight,
      tissue injury, oedema and inflammatory cell infiltration in the hepatocytes were
      found in the A group. These symptoms were remarkably alleviated in animals
      treated with artemisinin. Artemisinin can inhibit the activation of NF-kB and the
      expression of inflammatory cytokines inducible nitric oxide synthase. Besides, it
      can also enhance the stability of liver cell membrane, and reduce the damage of
      liver cell membrane and liver cell. Artemisinin showed a protective effect
      against chronic alcohol poisoning and it has a great potential for the clinical
      application to treat the liver injury induced by alcohol.

PMID- 28448817
TI  - Automated detection of pathologic white matter alterations in Alzheimer's disease
      using combined diffusivity and kurtosis method.
AB  - Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) are important
      diffusion MRI techniques for detecting microstructure abnormities in diseases
      such as Alzheimer's. The advantages of DKI over DTI have been reported generally;
      however, the indistinct relationship between diffusivity and kurtosis has not
      been clearly revealed in clinical settings. In this study, we hypothesize that
      the combination of diffusivity and kurtosis in DKI improves the capacity of DKI
      to detect Alzheimer's disease compared with diffusivity or kurtosis alone.
      Specifically, a support vector machine-based approach was applied to combine
      diffusivity and kurtosis and to compare different indices datasets. Strict
      assessments were conducted to ensure the reliability of all classifiers. Then,
      data from the optimized classifiers were used to detect abnormalities. With the
      combination, high accuracy performances of 96.23% were obtained in 53 subjects,
      including 27 Alzheimer's patients. More highly scored abnormal regions were
      selected by the combination than alone. The results revealed that more precise
      diffusivity and complementary kurtosis mainly contributed to the high performance
      of the combination in DKI. This study provides further understanding of DKI and
      the relationship between diffusivity and kurtosis in pathologic white matter
      alterations in Alzheimer's disease.

PMID- 28448818
TI  - PEGylated bilirubin nanoparticle as an anti-oxidative and anti-inflammatory
      demulcent in pancreatic islet xenotransplantation.
AB  - Transplanted islets suffer hypoxic stress, which leads to nonspecific
      inflammation. This is the major cause of islet graft failure during the early
      stage of intrahepatic islet transplantation. Although bilirubin has shown potent
      anti-oxidative and anti-inflammatory functions, its clinical applications have
      been limited due to its insolubility and short half-life. To overcome this
      problem, novel amphiphilic bilirubin nanoparticles are designed. Hydrophilic
      poly(ethylene glycol) (PEG) is conjugated to the hydrophobic bilirubin molecule.
      Then, the PEG-bilirubin conjugates form nanoparticles via self-assembly, i.e., so
      called to BRNPs. BRNPs can protect islet cells not only from chemically induced
      oxidative stress by scavenging reactive oxygen species molecules, but also from
      activated macrophages by suppressing cytokine release. Importantly, in vivo
      experiments demonstrate that BRNP treatment can dramatically and significantly
      prolong islet graft survival compared to bilirubin treatment. In addition,
      immunohistochemical analysis shows BRNPs have potent anti-oxidative and anti
      inflammatory capabilities. Collectively, novel BRNPs can be a new potent remedy
      for successful islet transplantation.

PMID- 28448819
TI  - Construction of three-dimensional vascularized functional human liver tissue
      using a layer-by-layer cell coating technique.
AB  - The creation of artificial liver tissue is an active area of research due to the
      shortage of donors for liver transplantation. Here we investigated whether a
      simple and efficient cell coating technique developed in our laboratory could be
      used to generate functional vascularized liver tissue. This technique creates
      three-dimensional tissue by loading cells sterically onto other cells that have
      been coated with layer-by-layer (LbL) nanofilms of fibronectin and gelatin, two
      extracellular matrix proteins. We used this technique to construct homogenous,
      dense, well-vascularized liver tissue from cryopreserved human primary
      hepatocytes, human umbilical vein endothelial cells, and normal human dermal
      fibroblasts. Using LbL cell coating technique resulted in higher cellular
      function in terms of human albumin production (P < 0.01) and cytochrome P450
      activity (P < 0.01) in vitro. Furthermore, after being transplanted
      subcutaneously into NOD/SCID mice, the vascularized liver tissue showed greater
      albumin production in the early stage than non-vascularized tissue or a
      hepatocyte suspension (P < 0.01). Histological examination demonstrated that
      compare to non-vascularized tissue, there were many less-morphologically changed
      and intact hepatocytes in the vascularized tissue. This cell coating technique
      would be applicable to the generation of vascularized functional liver tissue for
      regenerative medicine in the future.

PMID- 28448820
TI  - Is there a link between biological parents' insight into their offspring's
      schizophrenia and their cognitive functioning, expressed emotion and knowledge
      about disorder?
AB  - BACKGROUND: Recent studies suggest that parents' awareness of their offspring's
      schizophrenia could influence their offspring's insight. Low patient insight is
      linked to impairment of specific cognitive abilities, and biological parents of
      schizophrenia patients have impaired capacities in these same domains. However,
      little is known about what specific socio-demographic, affective or cognitive
      factors may influence biological parents' awareness of their offspring's disease.
      METHOD: Data were drawn from 41 patient-parent dyads. Insight was assessed with a
      modified version of Amador's Scale to assess Unawareness of Mental Disorders,
      exploring dimensions of parents' awareness and attribution of their offspring's
      illness and symptoms. RESULTS: Higher educational levels, better working memory
      and executive functioning of parents were associated with better attribution of
      their offspring's symptoms to schizophrenia. CONCLUSIONS: Parents' insight into
      their offspring's schizophrenia is associated with cognitive abilities. This must
      be taken into account when developing family interventions.

PMID- 28448821
TI  - The implications of war captivity and long-term psychopathology trajectories for
      telomere length.
AB  - BACKGROUND: Previous findings have demonstrated the link between trauma, its
      psychopathological aftermath and cellular aging, as reflected in telomere length.
      However, as long-term examinations of psychopathology following trauma are
      scarce, very little is known regarding the repercussions of depression and PTSD
      trajectories of psychopathology for telomeres. The current study examined the
      implications of war captivity and depression/PTSD trajectories on telomere
      length. METHODS: Ninety-nine former prisoners of war (ex-POWs) from the 1973 Yom
      Kippur War were evaluated for depression and PTSD at 18, 30, 35 and 42 years
      after the war. Data on leukocyte telomere length of ex-POWs and 79 controls was
      collected 42 years after the war. RESULTS: Ex-POWs had shorter telomeres compared
      to controls (Cohen's d=.5 indicating intermediate effect). Ex-POWs with chronic
      depression had shorter telomeres compared to those with delayed onset of
      depression (Cohen's d=4.89), and resilient ex-POWs (Cohen's d= 3.87), indicating
      high effect sizes. PTSD trajectories were not implicated in telomere length
      (Partial eta2=.16 and p=.11). CONCLUSION: The findings suggest that the
      detrimental ramifications of war captivity are extensive, involving premature
      cellular senesces. These findings further point to the wear-and-tear effect of
      long-term depression, but not PTSD, on telomere length. Explanations for the
      findings are discussed.

PMID- 28448822
TI  - hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein
      phosphatases.
AB  - The maintenance of genomic stability is essential for cellular viability and the
      prevention of diseases such as cancer. Human single-stranded DNA-binding protein
      1 (hSSB1) is a protein with roles in the stabilisation and restart of stalled DNA
      replication forks, as well as in the repair of oxidative DNA lesions and double
      strand DNA breaks. In the latter process, phosphorylation of threonine 117 by the
      ATM kinase is required for hSSB1 stability and efficient DNA repair. The
      regulation of hSSB1 in other DNA repair pathways has however remained unclear.
      Here we report that hSSB1 is also directly phosphorylated by DNA-PK at serine
      residue 134. While this modification is largely suppressed in undamaged cells by
      PPP-family protein phosphatases, S134 phosphorylation is enhanced following the
      disruption of replication forks and promotes cellular survival. Together, these
      data thereby represent a novel mechanism for hSSB1 regulation following the
      inhibition of replication.

PMID- 28448823
TI  - Accumulative effects of indoor air pollution exposure on leukocyte telomere
      length among non-smokers.
AB  - Indoor air pollution is an important environmental factor that contributes to the
      burden of various diseases. Long-term exposure to ambient air pollution is
      associated with telomere shortening. However, the association between chronic
      indoor air pollution from household fuel combustion and leukocyte telomere length
      has not been studied. In our study, 137 cancer-free non-smokers were recruited.
      Their exposure levels to indoor air pollution from 1985 to 2014 were assessed
      using a face-to-face interview questionnaire, and leukocyte telomere length (LTL)
      was measured using a monochrome multiplex quantitative PCR method. Accumulative
      exposure to solid fuel usage for cooking was negatively correlated with LTL. The
      LTL of residents who were exposed to solid fuel combustion for three decades (LTL
      = 0.70 +/- 0.17) was significantly shorter than that of other populations. In
      addition, education and occupation were related to both exposure to solid fuel
      and LTL. Sociodemographic factors may play a mediating role in the correlation
      between leukocyte telomere length and environmental exposure to indoor air
      pollution. In conclusion, long-term exposure to indoor air pollution may cause
      LTL dysfunction.

PMID- 28448824
TI  - A new quantitative method to assess disproportionately enlarged subarachnoid
      space (DESH) in patients with possible idiopathic normal pressure hydrocephalus:
      The SILVER index.
AB  - OBJECTIVES: Preoperative diagnosis of idiopathic normal-pressure hydrocephalus
      (iNPH) remains challenging. Recently, the presence of disproportionally enlarged
      subarachnoid spaces and hydrocephalus (DESH) on diagnostic images has been linked
      to clinical improvement after ventriculoperitoneal (VP) shunt placement. In this
      study we describe a new quantitative method to assess DESH on CT scans and to
      evaluate its prognostic value. PATIENTS AND METHODS: A multiplanar reconstruction
      software was used to retrospectively evaluate prospectively collected
      radiological data (CT scans) of 26 controls and 29 consecutive patients that
      underwent VP shunt placement for possible iNPH. The ratio between the areas of
      the sylvian fissure and the subarachnoid space at the vertex was calculated
      (SILVER index). The diagnostic accuracy of the SILVER index and the estimate of
      the best cut-point were assessed using ROC analysis. RESULTS: The mean value of
      the SILVER index was 11.52+/-14.27 in the study group and 1.68+/-0.98 in the
      control group (p-value<0.0001). The area under the ROC curve for the SILVER index
      was 0.903 (95% CI 0.813-0.994). A cut-off value for the SILVER index of 3.75 was
      extrapolated with a sensitivity and specificity of 0.828 and 0.962 respectively.
      CONCLUSIONS: The SILVER index is a reliable tool to easily quantify DESH on CT
      scans of patients with suspected iNPH. Its high sensitivity and specificity
      should encourage further investigations in order to confirm its clinical utility.

PMID- 28448825
TI  - Health policy in the concertacion era (1990-2010): Reforms the chilean way.
AB  - The Chilean health system has experienced important transformations in the last
      decades with a neoliberal turn to privatization of the health insurance and
      healthcare market since the Pinochet reforms of the 1980s. During 20 years of
      center-left political coalition governments several reforms were attempted to
      regulate and reform such markets. This paper analyzes regulatory policies for the
      private health insurance and health care delivery market, adopted during the 1990
      2010 period. A framework of variation in market types developed by Gingrich is
      adopted as analytical perspective. The set of policies advanced in this period
      could be expected to shift the responsibility of access to care from individuals
      to the collective and give control to the State or the consumers vis a vis
      producers. Nevertheless, the effect of the implemented reforms has been mixed.
      Regulations on private health insurers were ineffective in terms of shifting
      power to the consumer or the state. In contrast, the healthcare delivery market
      showed a trend of increasing payers' and consumers' control and the set of
      implemented reforms partially steered the market toward collective responsibility
      of access by creating a submarket of guaranteed services (AUGE) with lower
      copayments and fully funded services. Emerging unintended consequences of the
      adopted policies and potential explanations are discussed. In sum, attempts to
      use regulation to improve the collective dimension of the Chilean health system
      has enabled some progress, but several challenges had persisted.

PMID- 28448826
TI  - Generalized Anxiety Disorder, worry and attention to threat: A systematic review.
AB  - Among anxious populations, attention has been demonstrated to be preferentially
      biased to threatening material compared to neutral or other valenced material.
      Individuals who have high levels of trait worry, such as those with Generalized
      Anxiety Disorder (GAD), may be biased to threat but research has produced
      equivocal findings. This review aimed to systematically review the extant
      experimental literature to establish the current evidence of attentional bias to
      threat among trait worriers compared to healthy controls and other clinical
      populations. Twenty-nine published articles were included in the final review.
      There was strong evidence of a bias to threat among GAD patients compared to
      other groups and this was found across most experimental paradigms. Few studies
      had investigated this bias in non-clinical trait worriers. Among GAD patients
      this bias to threat was most strongly evidenced when visual threat material was
      in a verbal-linguistic format (i.e., words) rather than when in pictorial form
      (i.e., images or faces). The bias was also found across several domains of
      negative material, supporting the general nature of worry. Further research
      should look to examine the specific components of the threat bias in GAD, as well
      as investigating the bias to threat in trait worriers.

PMID- 28448827
TI  - Dopamine, cognitive biases and assessment of certainty: A neurocognitive model of
      delusions.
AB  - This paper examines the evidence that delusions can be explained within the
      framework of a neurocognitive model of how the brain assesses certainty. Here,
      'certainty' refers to both low-level interpretations of one's environment and
      high-level (conscious) appraisals of one's beliefs and experiences. A model is
      proposed explaining how the brain systems responsible for assigning certainty
      might dysfunction, contributing to the cause and maintenance of delusional
      beliefs. It is suggested that delusions arise through a combination of perturbed
      striatal dopamine and aberrant salience as well as cognitive biases such as the
      tendency to jump to conclusions (JTC) and hypersalience of evidence-hypothesis
      matches. The role of emotion, stress, trauma and sociocultural factors in forming
      and modifying delusions is also considered. Understanding the mechanisms involved
      in forming and maintaining delusions has important clinical implications, as
      interventions that improve cognitive flexibility (e.g. cognitive remediation
      therapy and mindfulness training) could potentially attenuate neurocognitive
      processes.

PMID- 28448828
TI  - Note on in situ (scanning) transmission electron microscopy study of liquid
      samples.
AB  - Liquid cell (scanning) transmission electron microscopy has been developed
      rapidly, using amorphous SiNx membranes as electron transparent windows. The
      current interpretations of electron beam effects are mainly based on radiolytic
      processes. In this note, additional effects of the electric field due to electron
      beam irradiation are discussed. The electric field can be produced by the charge
      accumulation due to the emission of secondary and Auger electrons. Besides
      various beam-induced phenomena, such as nanoparticle precipitation and gas bubble
      formation and motion, two other effects need to be considered; one is the change
      of Gibbs free energy of nucleation and the other is the violation of Brownian
      motion due to ion drifting driven by the electric field.

PMID- 28448829
TI  - Consequences of the CMR effect on EELS in TEM.
AB  - Double perovskite oxides have gained in importance and exhibit negative
      magnetoresistance, which is known as colossal magnetoresistance (CMR) effect.
      Using a La2CoMnO6 (LCM) thin film layer, we proved that the physical consequences
      of the CMR effect do also influence the electron energy loss spectrometry (EELS)
      signal. We observed a change of the band gap at low energy losses and were able
      to study the magnetisation with chemical sensitivity by employing energy loss
      magnetic chiral dichroism (EMCD) below the Curie temperature TC, where the CMR
      effect becomes significant.

PMID- 28448830
TI  - Biogenesis of secondary mycogenic minerals related to wall paintings
      deterioration process.
AB  - Present study addresses potential of fungal strains, isolated from deteriorated
      mural paintings and surrounding air environment of the Church of the Holy
      Ascension in Veliki Krcimir (Serbia), to precipitate mycogenic minerals, when
      cultivated on agarized B4 medium. Utilizing culture-based isolation methods, 38
      filamentous fungi were obtained in total, 23 from mural paintings and 15 from
      air, respectively, mainly ascomycetes, while Bjerkandera adusta and Thanatephorus
      cucumeris were only basidiomycetes. A total of 31 of 38 fungal isolates, more
      than 80%, were able to form minerals of different morphologies and variable size,
      determined via SEM-EDS and XRPD, to be either calcite or calcite and weddellite
      association. Among screened fungi, all Penicillium, Chaetomium and Cladosporium
      isolates, as well as most of the Aspergillus isolates (8/11) precipitated
      minerals, whereas cultures of Bionectria, Bjerkandera, and Seimatosporium
      isolates lacked any observable crystal forms. With the exception of two
      Alternaria alternata strains, no apparent disparity in potential to precipitate
      minerals in general, or form particular crystal phase was documented among the
      air and mural paintings isolates. Possible mechanisms of fungal mineralization of
      calcite and weddellite are further proposed. In addition to providing
      experimental evidence for fungal induced precipitation of oxalate and carbonate
      minerals, presented data suggest that fungal activity could be an important
      factor in a weathering process affecting cultural heritage exhibited and stored
      in inadequate conditions. Implementation of B4 plate assay for screening of
      mineralization potential of the isolated fungi could be used to assess
      biodegradative risk mycobiota pose to the mural paintings, so appropriate
      conservation measures may be utilized.

PMID- 28448832
TI  - Fabrication of a novel Z-scheme g-C3N4/Bi4O7 heterojunction photocatalyst with
      enhanced visible light-driven activity toward organic pollutants.
AB  - In this work, highly efficient g-C3N4/Bi4O7 heterojunction photocatalysts have
      been successfully fabricated by a facile method. Compared with the bare
      photocatalysts, the obtained g-C3N4/Bi4O7 hybrid photocatalysts exhibited
      efficient degradation activity toward methylene blue (MB), phenol, rhodamine B
      (RhB), and bisphenol A (BPA) under visible light irradiation. The influences of
      different g-C3N4 contents on the photocatalytic efficiency of the hybrid
      photocatalysts have been investigated. The results revealed that the g-C3N4/Bi4O7
      with g-C3N4 mass ratio of 30% exhibited the best photocatalytic activity. The
      activity enhancement should be ascribed to the improved visible light adsorption
      as well as the effective Z-scheme charge transfer according to the energy band
      theory. The UV-vis diffuse reflectance spectra (DRS) shows that the absorption
      edge of g-C3N4 move towards longer wavelength with the increment of Bi4O7
      component. The strong connection between g-C3N4 and Bi4O7 was investigated using
      X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS).
      Subsequently, the effective Z-scheme charge transfer has also been verified by
      using transient photocurrent measurements and electrochemical impedance
      spectroscopy. Controlled experiments proved that active species of O2- and h+
      were produced in the degradation system, which played the major role in the
      degradation of MB. A possible Z-scheme degradation mechanism over g-C3N4/Bi4O7
      hybrid photocatalysts was proposed.

PMID- 28448831
TI  - Computer simulations analysis for determining the polarity of charge generated by
      high energy electron irradiation of a thin film.
AB  - Detailed simulations are necessary to correctly interpret the charge polarity of
      electron beam irradiated thin film patch. Relying on systematic simulations we
      provide guidelines and movies to interpret experimentally the polarity of the
      charged area, to be understood as the sign of the electrostatic potential
      developed under the beam with reference to a ground electrode. We discuss the two
      methods most frequently used to assess charge polarity: Fresnel imaging of the
      irradiated area and Thon rings analysis. We also briefly discuss parameter
      optimization for hole free phase plate (HFPP) imaging. Our results are
      particularly relevant to understanding contrast of hole-free phase plate imaging
      and Berriman effect.

PMID- 28448833
TI  - Facile green synthesis of a Co3V2O8 nanoparticle electrode for high energy
      lithium-ion battery applications.
AB  - In the present study, a metal-organic framework (MOF) derived from a facile water
      assisted green precipitation technique is employed to synthesize phase-pure
      cobalt vanadate (Co3V2O8, CVO) anode for lithium-ion battery (LIB) application.
      The material obtained by this eco-friendly method is systematically characterized
      using various techniques such as powder X-ray diffraction (PXRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), X-ray
      photoelectron spectroscopy (XPS) and N2 adsorption-desorption measurements. By
      using as an anode, an initial discharge capacity of 1640mAhg-1 and a reversible
      capacity of 1194mAhg-1 are obtained at the applied current densities after the
      240th cycle (2Ag-1 for 200 cycles followed by 0.2Ag-1 for 40 cycles). Moreover, a
      reversible capacity as high as 962mAhg-1 is retained at high current densities
      even after 240 cycles (4Ag-1 for 200 cycles followed by 2Ag-1 for 40 cycles),
      revealing the long life stability of the electrode. Significantly, CVO anode
      composed of fine nanoparticles (NPs) registered a substantial rate performance
      and reversible specific capacities of 275, 390, 543 and 699mAhg-1 at high
      reversibly altered current densities of 10, 5, 2, and 1Ag-1, respectively.

PMID- 28448834
TI  - CMC prediction for ionic surfactants in pure water and aqueous salt solutions
      based solely on tabulated molecular parameters.
AB  - The critical micelle concentration (CMC) of various surfactants is difficult to
      predict accurately, yet often necessary to do in both industry and science.
      Hence, quantum-chemical software packages for precise calculation of CMC were
      developed, but they are expensive and time consuming. We show here an easy method
      for calculating CMC with a reasonable accuracy. Firstly, CMC0 (intrinsic CMC,
      absent added salt) was coupled with quantitative structure - property
      relationship (QSPR) with defined by us parameter "CMC predictor" f1. It can be
      easily calculated from a number of tabulated molecular parameters - the
      adsorption energy of surfactant's head, the adsorption energy of its methylene
      groups, its number of carbon atoms, the specific adsorption energy of its counter
      ions, their valency and bare radius. We applied this method to determine CMC0 to
      a test set of 11 ionic surfactants, yielding 7.5% accuracy. Furthermore, we
      calculated CMC in the presence of added salts using the advanced version of
      Corrin-Harkins equation, which accounts for both the intrinsic and the added
      counter-ions. Our salt-saturation multiplier, accounts for both the type and
      concentration of the added counter-ions. We applied our theory to a test set
      containing 11 anionic/cationic surfactant+salt systems, achieving 8% accuracy.

PMID- 28448835
TI  - Continuous production of polymer nanoparticles using a membrane-based flow cell.
AB  - We demonstrate the surfactant-free production of polymer nanoparticles using a
      continuous membrane-based tangential flow cell. Co-current streams of water and
      polymethylmethacrylate (PMMA)/acetone/water solution were separated by a porous
      regenerated cellulose (RC) membrane. The water concentration in the PMMA solution
      was adjusted so that as additional water diffused through the RC membrane, the
      PMMA solution composition crossed the two phase boundary to precipitate PMMA
      nanoparticles. The size of these nanoparticles varied with the concentration of
      the PMMA feed and the amount of water diffusing across the membrane. The size
      distribution of PMMA particles produced in a continuous flow membrane cell was
      much narrower than those produced by drop-wise water addition or batch dialysis
      precipitation of PMMA particles. A continuous production of polymer nanoparticles
      of high purity and narrow polydispersity are important requirements for
      biomedical applications such as delivering therapeutics.

PMID- 28448836
TI  - Breast cancer detection in automated 3D breast ultrasound using iso-contours and
      cascaded RUSBoosts.
AB  - Automated 3D breast ultrasound (ABUS) is a new popular modality as an adjunct to
      mammography for detecting cancers in women with dense breasts. In this paper, a
      multi-stage computer aided detection system is proposed to detect cancers in ABUS
      images. In the first step, an efficient despeckling method called OBNLM is
      applied on the images to reduce speckle noise. Afterwards, a new algorithm based
      on isocontours is applied to detect initial candidates as the boundary of masses
      is hypo echoic. To reduce false generated isocontours, features such as
      hypoechoicity, roundness, area and contour strength are used. Consequently, the
      resulted candidates are further processed by a cascade classifier whose base
      classifiers are Random Under-Sampling Boosting (RUSBoost) that are introduced to
      deal with imbalanced datasets. Each base classifier is trained on a group of
      features like Gabor, LBP, GLCM and other features. Performance of the proposed
      system was evaluated using 104 volumes from 74 patients, including 112 malignant
      lesions. According to Free Response Operating Characteristic (FROC) analysis, the
      proposed system achieved the region-based sensitivity and case-based sensitivity
      of 68% and 76% at one false positive per image.

PMID- 28448837
TI  - Genetic analysis of meat quality traits in maternal lines of rabbit and their
      diallel cross.
AB  - Young rabbits, the dams of which came from a full diallel cross among four
      maternal lines (A, V, H and LP) and the sires from a single paternal line (R),
      that produce sixteen genetic groups, was carried out to evaluate the genetic
      groups and to estimate the crossbreeding genetic parameters of meat quality. The
      meat quality traits were recorded by NIRS from a sample of 285 longissimus
      lumborum muscles. Crossbreeding parameters were estimated according to Dickerson
      model. No differences in protein were found. The line A had significant
      differences with V line for intramuscular fat, and fatty acids groups.
      Significant differences for these traits appeared between the crossbred AH and VV
      (in favor of AH). As conclusion, the significant contrasts between genetic types
      for chemical composition of the meat are mainly consequence of direct-maternal
      genetic effects, having grandmaternal and maternal heterosis effects a less
      relevant role.

PMID- 28448838
TI  - Effects of feeding steers extruded flaxseed on its own before hay or mixed with
      hay on animal performance, carcass quality, and meat and hamburger fatty acid
      composition.
AB  - The objective of the present experiment was to determine if carcass quality and
      fatty acid profiles of longissimus thoracis (LT) and hamburger would be affected
      by feeding steers extruded flaxseed on its own followed by hay (non-TMR) compared
      to when hay and extruded flaxseed were fed together (TMR). Forty-eight steers in
      six pens were assigned to TMR or non-TMR for an average of 242days. Dry matter
      intake was lower for non-TMR versus TMR steers (10.56 vs. 11.42kg/d; P=0.02), but
      final live weight (610+/-0.50kg) and average daily gain (1.18+/-0.02kg/d) did not
      differ. Compared to TMR, feeding non-TMR enriched LT and hamburger with alpha
      linolenic acid (ALA; 18:3n-3) by 14%, vaccenic acid (VA; t11-18:1) by 44%,
      rumenic acid (RA; c9,t11-18:2) by 40%, and conjugated linolenic acid (CLnA) by
      58%. Overall, feeding extruded flaxseed separately from hay in a non-TMR was more
      effective at enhancing deposition of ALA, VA, RA and CLnA in beef.

PMID- 28448839
TI  - Stimulus-response links and the backward crosstalk effect - A comparison of
      forced- and free-choice tasks.
AB  - In dual-tasks, characteristics of Task 2 responses can already affect performance
      in the preceding Task 1. This is called the backward crosstalk effect (BCE). To
      account for the BCE, it has been suggested that the appearance of the Task 2
      stimulus automatically projects activation onto the corresponding response
      through (transient or direct) stimulus-response (S-R) links. One way to
      investigate this claim is to compare the size of the BCE for tasks where S-R
      links are differently strong. To this end, we here compared BCEs for forced- vs.
      free-choice tasks, with the S-R links assumed to be stronger in the former than
      in the latter task. In Experiments 1 and 2, Task 1 was either forced-choice or
      free-choice and Task 2 always forced-choice, and in Experiment 3 this order was
      reversed. A BCE was observed in all experiments with the forced-choice tasks, but
      in response times it was smaller in Experiments 1 and 2 and absent in Experiment
      3 with the free-choice task. However, in free-choice Task 1 responses, a bias
      towards selecting the response required in Task 2 was observed. These results
      suggest that the strength of S-R links plays a role in determining the size of
      the BCE. Relations to other studies and alternative explanations are discussed.

PMID- 28448840
TI  - A cocktail of volatile compounds emitted from Alcaligenes faecalis JBCS1294
      induces salt tolerance in Arabidopsis thaliana by modulating hormonal pathways
      and ion transporters.
AB  - In our previous study we showed that volatile organic compounds (VOCs) from
      Alcaligenes faecalis JBCS1294 (JBCS1294) induced tolerance to salt stress in
      Arabidopsis thaliana by influencing the auxin and gibberellin pathways and
      upregulating the expression of key ion transporters. The aim of this study was to
      evaluate the contribution of each VOC and blends of the VOCs on the induction of
      salt tolerance and signaling pathways. The key VOCs emitted from JBCS1294 were
      dissolved in lanolin and applied to one side of bipartite I-plates that contained
      Arabidopsis seeds on Murashige and Skoog (MS) media supplemented with NaCl on the
      other side. Changes in plant growth were investigated using Arabidopsis mutant
      lines and hormone inhibitors, and gene expression was assessed by real-time PCR
      (qPCR). Among the VOCs, butyric acid conferred salt tolerance over a
      concentration range of 5.6MUM (10ng)-56mM (100MUg), whereas propionic and benzoic
      acid were effective at micromolar doses. Intriguingly, the optimized cocktail of
      the three VOCs increased fresh weight of Arabidopsis under salt stress compared
      to that achieved with each single compound. However, Arabidopsis growth was not
      promoted by the VOCs without salt stress. Exogenous indole-3-acetic acid (IAA)
      application arrested salt tolerance or growth promotion of Arabidopsis induced by
      volatiles from propionic acid, but not from butyric acid and an optimized
      volatile mixture of butyric acid, propionic acid, and benzoic acid (1PBB). High
      and intense auxin-responsive DR5:GUS activity was observed in the roots of
      Arabidopsis grown on media without salt via 1PBB, butyric acid, and benzoic acid.
      Growth promotion by the cocktail was inhibited in the eir1 mutant and in Col-0
      plants treated with inhibitors of auxin and gibberellin. The present study
      clearly demonstrated the effects of individual VOCs and blends of VOCs from a
      rhizobacterial strain on the induction of salt stress. The results with the blend
      of VOCs, which mimics bacterial emissions in nature, may lead to a deeper
      understanding of the interaction between rhizobacteria and plants.

PMID- 28448841
TI  - Why computer models help to understand developmental processes.
AB  - It is argued that simulating psychological processes by means of computer models
      is a valuable technique to increase our understanding of adolescent developmental
      processes. Modelling offers possibilities to test hypotheses that cannot be
      reached by designing empirical studies only and it allows us to investigate
      adolescent development as the complex and non-linear process that it is.

PMID- 28448842
TI  - Risk of incident myocardial infarction by gender: Interactions with serum lipids,
      blood pressure and smoking. The Tromso Study 1979-2012.
AB  - BACKGROUND AND AIMS: Overall, men have roughly twice the risk of myocardial
      infarction (MI) compared to women, but what causes this contrast is unclear.
      Identification of subgroups where the gender contrast in risk is particularly low
      or high, may provide new insight. In the search for such subgroups, we focus on
      gender-specific effects of established coronary heart disease (CHD) risk factors.
      Heterogeneity across age groups is also explored. METHODS: Population-based
      prospective study from Tromso, Norway, comprising 33,859 individuals (51% women);
      2746 individuals (854 women) received a diagnosis of MI during follow-up at ages
      35-94 years. Incidence rate ratios (IRR) were calculated as estimates of relative
      risk in Poisson regression analyses. RESULTS: The association between total
      cholesterol and risk of MI was stronger for men than women, and IRR for men vs.
      women accordingly increased with increasing cholesterol, but the risk was higher
      for men in all subgroups (IRR in range 1.63-3.27), except among older people with
      low cholesterol levels. The adverse effect of increasing blood pressure (BP) was
      stronger for women, and IRR for gender diminished with increasing systolic (from
      3.90 to 1.38) and diastolic BP (from 2.87 to 1.54). The gender contrast in risk
      was also substantially reduced in smokers >=75 years. Associations with high
      density lipoprotein cholesterol (HDL-C) did not differ between genders.
      CONCLUSIONS: Gender heterogeneity in associations with total cholesterol but not
      HDL-C indicates gender differences in associations with non-HDL-C. The stronger
      association with BP in women may relate to more severe hypertension-induced left
      ventricular hypertrophy.

PMID- 28448843
TI  - Prediction of PM2.5 along urban highway corridor under mixed traffic conditions
      using CALINE4 model.
AB  - The present study deals with spatial-temporal distribution of PM2.5 along a
      highly trafficked national highway corridor (NH-2) in Delhi, India. Population
      residing in areas near roads and highways of high vehicular activities are
      exposed to high levels of PM2.5 resulting in various health issues. The spatial
      extent of PM2.5 has been assessed with the help of CALINE4 model. Various input
      parameters of the model were estimated and used to predict PM2.5 concentration
      along the selected highway corridor. The results indicated that there are many
      factors involved which affects the prediction of PM2.5 concentration by CALINE4
      model. In fact, these factors either not considered by model or have little
      influence on model's prediction capabilities. Therefore, in the present study
      CALINE4 model performance was observed to be unsatisfactory for prediction of
      PM2.5 concentration.

PMID- 28448844
TI  - Consequences of bioenergy wood extraction for landscape-level availability of
      habitat for dead wood-dependent organisms.
AB  - Stumps and slash resulting from forest clearcutting is used as a source of low
      net-carbon energy, but there are concerns about the consequences of biofuel
      extraction on biodiversity. Logging residues constitute potentially important
      habitats, since a large part of forest biodiversity is dependent on dead wood.
      Here we used snapshot field data from a managed forest landscape (25 000 ha) to
      predict landscape scale population changes of dead wood dependent organisms after
      extraction of stumps and slash after clearcutting. We did this by estimating
      habitat availability for all observed dead wood-dependent beetles, macrofungi,
      and lichens (380 species) in the whole landscape. We found that 53% of species
      occurred in slash or stumps. For most species, population declines after moderate
      extraction (<=30%) were small (<10% decline) because they mainly occur on other
      dead wood types. However, some species were only recorded in slash and stumps.
      Red listed species were affected by slash and stump extraction (12 species), but
      less often than other species. Beetles and fungi were more affected by stump
      extraction, while lichens were more affected by slash extraction. For beetles and
      lichens, extraction of a combination of spruce, pine and birch resulted in larger
      negative effects than if only extracting spruce, while for fungi tree species had
      little effect. We conclude that extensive extraction decreases the amount of
      habitat to such extent that it may have negative consequences on species
      persistence at the landscape level. The negative consequences can be limited by
      extracting only slash, or only logging residues from spruce stands.

PMID- 28448845
TI  - Use of aqueous two-phase PEG-salt systems for the removal of anionic surfactant
      from effluents.
AB  - Linear alkylbenzene sulfonates (LAS) are synthetic anionic surfactants that are
      extensively used in many industries. As a result, large volumes of effluents
      containing high levels of these compounds are discharged into water bodies,
      causing risks to aquatic flora and fauna. Then, there is a need for
      environmentally safe and economically viable technologies for the removal of LAS
      from aqueous matrices. The present work evaluates the use of aqueous two-phase
      systems (ATPS) composed of PEG and sulfate salts for this purpose, considering
      the effects of tie line length (TLL), molar mass of polymer, and type of cation
      forming salt on the partitioning behavior of LAS. All the LAS partition
      coefficient (KLAS) values were greater than unity, and the LAS extraction
      efficiencies (%ELAS) were higher than 97%. The system consisting of PEG 1500 +
      (NH4)2SO4 + H2O provided the highest KLAS (1083.34) and %ELAS (99.9%), indicating
      that the method provided good extraction of LAS to the top phase. This system was
      applied using a real effluent sample in laboratory-scale experiments as well as
      in bench-scale batch trials. The results obtained at the laboratory scale showed
      %ELAS values greater than 98%, while the best KLAS value obtained in the batch
      experiments was 8.50 (+/-1.75) (%ELAS = 78.17%). These values demonstrated the
      potential of ATPS for the removal of LAS from industrial effluents.

PMID- 28448846
TI  - Upcrowding energy co-operatives - Evaluating the potential of crowdfunding for
      business model innovation of energy co-operatives.
AB  - Practice and theory have proven the relevance of energy co-operatives for civic
      participation in the energy turnaround. However, due to a still low awareness and
      changing regulation, there seems an unexploited potential of utilizing the legal
      form 'co-operative' in this context. The aim of this study is therefore to
      investigate the crowdfunding implementation in the business model of energy co
      operatives in order to cope with the mentioned challenges. Based on a theoretical
      framework, we derive a Business Model Innovation (BMI) through crowdfunding
      including synergies and differences. A qualitative study design, particularly a
      multiple-case study of energy co-operatives, was chosen to prove the BMI and to
      reveal barriers. The results show that although most co-operatives are not
      familiar with crowdfunding, there is strong potential in opening up predominantly
      local structures to a broader group of members. Building on this, equity-based
      crowdfunding is revealed to be suitable for energy co-operatives as BMI and to
      accompany other challenges in the same way.

PMID- 28448847
TI  - Lactic acid fermentation of human urine to improve its fertilizing value and
      reduce odour emissions.
AB  - During storage of urine, urea is biologically decomposed to ammonia, which can be
      lost through volatilization and in turn causes significant unpleasant smell. In
      response, lactic acid fermentation of urine is a cost-effective technique to
      decrease nitrogen volatilization and reduce odour emissions. Fresh urine (pH =
      5.2-5.3 and NH4+-N = 1.2-1.3 g L-1) was lacto-fermented for 36 days in closed
      glass jars with a lactic acid bacterial inoculum from sauerkraut juice and
      compared to untreated, stored urine. In the lacto-fermented urine, the pH was
      reduced to 3.8-4.7 and the ammonium content by 22-30%, while the pH of the
      untreated urine rose to 6.1 and its ammonium content increased by 32% due to urea
      hydrolysis. The concentration of lactic acid bacteria in lacto-fermented urine
      was 7.3 CFU ml-1, suggesting that urine is a suitable growth medium for lactic
      acid bacteria. The odour of the stored urine was subjectively perceived by four
      people to be twice as strong as that of lacto-fermented samples. Lacto-fermented
      urine induced increased radish germination compared to stored urine (74-86%
      versus 2-31%). Adding a lactic acid bacterial inoculum to one week old urine in
      the storage tanks in a urine-diverting dry toilet reduced the pH from 8.9 to 7.7
      after one month, while the ammonium content increased by 35%, probably due to the
      high initial pH of the urine. Given that the hydrolyzed stale urine has a high
      buffering capacity, the lactic acid bacterial inoculum should be added to the
      urine storage tank of a UDDT before urine starts to accumulate there to increase
      the efficiency of the lactic acid fermentation.

PMID- 28448848
TI  - Transmissible gastroenteritis virus infection induces NF-kappaB activation
      through RLR-mediated signaling.
AB  - Transmissible gastroenteritis virus (TGEV) is a porcine enteric coronavirus which
      causes lethal severe watery diarrhea in piglets. The pathogenesis of TGEV is
      strongly associated with inflammation. In this study, we found that TGEV
      infection activates transcription factors NF-kappaB, IRF3 and AP-1 in a time- and
      dose-dependent manner in porcine kidney cells. Treatment with the NF-kappaB
      specific inhibitor BAY11-7082 significantly decreased TGEV-induced
      proinflammatory cytokine production, but did not affect virus replication.
      Phosphorylation of NF-kappaB subunit p65 and proinflammatory cytokine production
      were greatly decreased after knockdown of retinoic acid-inducible gene I (RIG-I)
      like receptors (RLRs) or its adaptors MAVS and STING, while only slight reduction
      was observed in cells following silencing of Toll-like receptor adaptors, MyD88
      and TRIF. Furthermore, TGEV infection significantly upregulated mRNA expression
      of RIG-I and MDA5. Taken together, our results indicate that the RLR signaling
      pathway is involved in TGEV-induced inflammatory responses.

PMID- 28448849
TI  - Regulation of the human papillomavirus type 16 late promoter by transcriptional
      elongation.
AB  - Transcripts from the late promoter of human papillomavirus type 16 (HPV16) are
      upregulated upon host cell differentiation. Differentiation-dependent transcript
      regulation is thought to sequester viral antigens in the uppermost epithelial
      layers, facilitating immune evasion. The mechanisms regulating late promoter
      upregulation during differentiation are poorly characterized. We show that the
      late promoter is upregulated at the transcriptional level and that the viral
      enhancer stimulates promoter activity. Using kinase inhibition and chromatin
      immunoprecipitation analysis, we show evidence for differentiation-dependent
      enhancement of transcript elongation. Three factors that promote transcript
      elongation, cyclin dependent kinase 9 (CDK9), CDK8 (a subunit of the Mediator
      complex), and bromodomain containing protein 4 (Brd4) are recruited to viral
      genomes upon differentiation, and each plays a role in promoter activity. These
      results shed light on the transcriptional processes utilized by HPV16 for proper
      regulation of gene expression during the viral life cycle.

PMID- 28448850
TI  - Perturbation of DROSHA and DICER expression by human papillomavirus 16
      oncoproteins.
AB  - Many tumors, including cervical carcinoma, show dysregulated expression of the
      microRNA processing machinery, specifically DROSHA and DICER. Some cervical
      cancers exhibit chromosome 5p amplifications and DROSHA is the most significantly
      upregulated transcript and is observed in all tumors with 5p gain. DROSHA and
      DICER mRNA levels, however, are higher in HPV positive cancer lines than in an
      HPV negative cervical carcinoma line. We show that high-risk HPV E6/E7 expression
      in HPV negative C33A cervical carcinoma cells and primary human epithelial cell
      causes increased expression of DROSHA and DICER mRNA and protein. Most
      importantly, many DROSHA regulated microRNAs are dysregulated in HPV16 E6/E7
      expressing cells. These results suggest that increased DROSHA levels contribute
      to HPV16 E6/E7 dysregulation of cellular microRNA expression.

PMID- 28448851
TI  - Accurate 3D reconstruction of bony surfaces using ultrasonic synthetic aperture
      techniques for robotic knee arthroplasty.
AB  - Robotically guided knee arthroplasty systems generally require an individualized,
      preoperative 3D model of the knee joint. This is typically measured using
      Computed Tomography (CT) which provides the required accuracy for preoperative
      surgical intervention planning. Ultrasound imaging presents an attractive
      alternative to CT, allowing for reductions in cost and the elimination of doses
      of ionizing radiation, whilst maintaining the accuracy of the 3D model
      reconstruction of the joint. Traditional phased array ultrasound imaging methods,
      however, are susceptible to poor resolution and signal to noise ratios (SNR).
      Alleviating these weaknesses by offering superior focusing power, synthetic
      aperture methods have been investigated extensively within ultrasonic non
      destructive testing. Despite this, they have yet to be fully exploited in medical
      imaging. In this paper, the ability of a robotic deployed ultrasound imaging
      system based on synthetic aperture methods to accurately reconstruct bony
      surfaces is investigated. Employing the Total Focussing Method (TFM) and the
      Synthetic Aperture Focussing Technique (SAFT), two samples were imaged which were
      representative of the bones of the knee joint: a human-shaped, composite distal
      femur and a bovine distal femur. Data were captured using a 5MHz, 128 element 1D
      phased array, which was manipulated around the samples using a robotic
      positioning system. Three dimensional surface reconstructions were then produced
      and compared with reference models measured using a precision laser scanner. Mean
      errors of 0.82mm and 0.88mm were obtained for the composite and bovine samples,
      respectively, thus demonstrating the feasibility of the approach to deliver the
      sub-millimetre accuracy required for the application.

PMID- 28448852
TI  - Reproducibility of scapular muscle activity in isokinetic shoulder flexion and
      extension.
AB  - Repetitive overhead movements have been identified as a main risk factor to
      develop shoulder complaints with scapular muscle activity being altered. Reliable
      assessment of muscle activity is essential to differentiate between symptomatic
      and asymptomatic individuals. Therefore, the present study aimed to investigate
      the intra- and inter-session reliability of scapular muscle activity during
      maximal isokinetic shoulder flexion and extension. Eleven asymptomatic adults
      performed maximum effort isokinetic shoulder flexion and extension (concentric
      and eccentric at 60 degrees /s) in a test-retest design. Muscle activity of the
      upper and lower trapezius and serratus anterior was assessed by sEMG. Root Mean
      Square was calculated for whole ROM and single movement phases of absolute and
      normalized muscle activity. Absolute (Bland-Altman analysis (Bias, LoA), Minimal
      detectable change (MDC)) and relative reliability parameters (Intraclass
      correlation coefficient (ICC), coefficient of variation (CV)/test-retest
      variability (TRV)) were utilized for the evaluation of reproducibility. Intra
      session reliability revealed ICCs between 0.56 and 0.98, averaged CVs of 18% and
      average MDCs of 81mV. Inter-session reliability resulted in ICCs between 0.13 and
      0.93, averaged TRVs of 21%, average MDCs of 15% and systematic and random error
      between -8+/-60% and 12+/-36%. Scapular muscle activity assessed in overhead
      movements can be measured reliably under maximum load conditions, though
      variability is dependent on the movement phase. Measurement variability does not
      exceed magnitudes of altered scapular muscle activities as reported in previous
      studies. Therefore, maximum load application is a promising approach for the
      evaluation of changes in scapular control related to pathologies.

PMID- 28448853
TI  - A cluster of aspartic residues in the extracellular loop II of PAR 4 is important
      for thrombin interaction and activation of platelets.
AB  - Thrombin activates platelets via proteolytic cleavage of protease-activated
      receptors (PARs) 1 and 4. The two PARs have distinct but complementary roles. The
      mechanisms responsible for PAR1 activation by thrombin have been extensively
      studied. However, much less is known regarding thrombin activation of PAR4,
      especially the potential involvement of regions of PAR4 other than the N
      terminal, which is bound to the catalytic site of thrombin. We have studied PAR4
      in S. cerevisiae strain MMY12, an expression system in which the GPCR receptors
      are connected to a Lac Z reporter gene resulting in increased beta-galactosidase
      activity. This approach was used to assess PAR4 mutants to evaluate the
      contribution of different aspartic residues in facilitating PAR4 activation.
      Furthermore, peptides mimicking parts of the PAR4 N-terminal and the second
      extracellular loop (ECLII) were tested for their ability to inhibit platelet
      activation by thrombin. Binding of these peptides to gamma-thrombin was studied
      by monitoring the decrease in tryptophan fluorescence intensity of thrombin. We
      conclude that not only the N-terminal but also the electronegative aspartic
      residues D224, D230 and D235 (located in ECLII) are be important for PAR4 binding
      to thrombin. We further suggest that they play a role for the tethered ligand
      binding to the receptor, as mutations also affected activation in response to a
      PAR4-activating peptide mimicking the new N-terminal formed after cleavage. This
      agrees with previous results on PAR1 and thrombin binding. We suggest that the
      ECLII of PAR4 could be a potential target for antithrombotic drug development.

PMID- 28448854
TI  - The combined use of analytical tools for exploring tetanus toxin and tetanus
      toxoid structures.
AB  - Aldehyde detoxification is a process used to convert toxin into toxoid for
      vaccine applications. In the case of tetanus toxin (TT), formaldehyde is used to
      obtain the tetanus toxoid (TTd), which is used either for the tetanus vaccine or
      as carrier protein in conjugate vaccines. Several studies have already been
      conducted to better understand the exact mechanism of this detoxification. Those
      studies led to the identification of a number of formaldehyde-induced
      modifications on lab scale TTd samples. To obtain greater insights of the changes
      induced by formaldehyde, we used three industrial TTd batches to identify
      repeatable modifications in the detoxification process. Our strategy was to
      combine seven analytical tools to map these changes. Mass spectrometry (MS),
      colorimetric test and amino acid analysis (AAA) were used to study modifications
      on amino acids. SDS-PAGE, asymmetric flow field flow fractionation (AF4),
      fluorescence spectroscopy and circular dichroism (CD) were used to study
      formaldehyde modifications on the whole protein structure. We identified 41
      formaldehyde-induced modifications across the 1315 amino acid primary sequence of
      TT. Of these, five modifications on lysine residues were repeatable across TTd
      batches. Changes in protein conformation were also observed using SDS-PAGE, AF4
      and CD techniques. Each analytical tool brought a piece of information regarding
      formaldehyde induced-modifications, and all together, these methods provided a
      comprehensive overview of the structural changes that occurred with
      detoxification. These results could be the first step leading to site-directed TT
      mutagenesis studies that may enable the production of a non-toxic equivalent
      protein without using formaldehyde.

PMID- 28448855
TI  - Glassy carbon electrode modified with 7,7,8,8-tetracyanoquinodimethane and
      graphene oxide triggered a synergistic effect: Low-potential amperometric
      detection of reduced glutathione.
AB  - A sensitive electrochemical sensor based on the synergistic effect of 7,7,8,8
      tetracyanoquinodimethane (TCNQ) and graphene oxide (GO) for low-potential
      amperometric detection of reduced glutathione (GSH) in pH 7.2 phosphate buffer
      solution (PBS) has been reported. This is the first time that the combination of
      GO and TCNQ have been successfully employed to construct an electrochemical
      sensor for the detection of glutathione. The surface of the glassy carbon
      electrode (GCE) was modified by a drop casting using TCNQ and GO. Cyclic
      voltammetric measurements showed that TCNQ and GO triggered a synergistic effect
      and exhibited an unexpected electrocatalytic activity towards GSH oxidation,
      compared to GCE modified with only GO, TCNQ or TCNQ/electrochemically reduced GO.
      Three oxidation waves for GSH were found at -0.05, 0.1 and 0.5V, respectively.
      Amperometric techniques were employed to detect GSH sensitively using a GCE
      modified with TCNQ/GO at -0.05V. The electrochemical sensor showed a wide linear
      range from 0.25 to 124.3MUM and 124.3MUM to 1.67mM with a limit of detection of
      0.15MUM. The electroanalytical sensor was successfully applied towards the
      detection of GSH in an eye drop solution.

PMID- 28448856
TI  - Impact of a risk-based follow-up in patients affected by gastrointestinal stromal
      tumour.
AB  - BACKGROUND: Follow-up aims to precociously identify recurrences, metastases or
      treatment-related adverse events so as to undertake the appropriate therapy.
      Guidelines admit lack of knowledge on optimal surveillance schedule, but suggest
      follow-up based on experts' opinion and risk stratification. To identify the
      impact, if any, of regular follow-up, we interrogated our prospectively collected
      database whether early detection of recurrences affected both clinical management
      and, likely, the outcome. PATIENTS AND METHODS: We required information to be
      available on primary surgery and >=3 degrees years of follow-up for non-recurring
      patients. We analysed recurrence characteristics (asymptomatic versus
      symptomatic, low- versus high tumour burden) and computed tomography (CT) scan
      counts to detect one recurrence. Kaplan-Meier method estimated recurrence-free
      survival (RFS), post-recurrence progression-free survival (PR-PFS), and disease
      specific overall survival (OS). Comparisons used Hazard ratios (HR) with 95%
      confidence intervals (CIs). Multivariate analyses employed the Cox proportional
      hazards model. All tests were two-sided. RESULTS: Between 01/2001 and 12/2012 we
      found 233 study-eligible patients. Estimated 5- and 10-year RFS were 61.8% and
      50.4%, respectively. After a 68-month median follow-up, we observed 94 (40.3%)
      recurrences [73/94 (77.7%) asymptomatic versus 21/94 (22.3%) symptomatic and
      45/94 (47.9%) low- versus 49/94 (52.1%) high tumour burden]. Multivariate
      analysis revealed that symptomatic and high tumour burden recurrences were highly
      predictive of both worse PR-PFS (HR:3.19, P < 0.001; HR:2.80, P = 0.003,
      respectively) and OS (HR:3.65, P < 0.001; HR:2.38, P = 0.026, respectively).
      Finally, 29 second (primary) cancers were detected during follow-up. CONCLUSIONS:
      Regular follow-up detects recurrences at an earlier stage and may be associated
      with a better PR-PFS and OS for these patients. In the absence of randomised
      trials, these evidences support follow-up effort and cost.

PMID- 28448857
TI  - Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup:
      Recommendations on incorporating patient-reported outcomes in clinical trials in
      epithelial ovarian cancer.
AB  - Despite the support for including patient-reported outcomes (PROs) and health
      related quality of life in clinical trials, there have been deficiencies in how
      these have been assessed and reported in epithelial ovarian cancer (EOC) clinical
      trials. To redress this, the 5th Ovarian Cancer Consensus Conference, included a
      plenary session entitled 'How to include PROs in clinical trials'. The
      perspective is a summary of the recommendations made by the Gynecologic Cancer
      InterGroup unanimously agreed on the importance of PROs and PRO end-points in EOC
      clinical trials. They recognised that effort must be made to ensure the integrity
      of collection of PRO data and to avoid missing data. PRO end-points should be
      based on the PRO hypotheses, be context specific and reflect the patient
      population and the objectives of treatment (e.g. first line, maintenance therapy,
      early or late relapse). The PRO end-points inform the choice of PRO measures used
      in the trial and how the results are analysed and reported. There was agreement
      that progression-free survival should be supported by PROs among patients with
      late relapse (platinum sensitive) and that progression-free survival alone was
      not sufficient as the primary end-point of clinical trials in patients with
      platinum resistant/refractory EOC and PROs should be included as either the
      primary/co-primary end-point in this subset of patients. Novel approaches to
      measure the benefit of palliative chemotherapy such as time until definitive
      deterioration of Health-Related Quality of Life were recommended. There was
      consensus to endorse the ISOQOL and CONSORT-PRO guidelines on the inclusion and
      reporting of PRO endpoints in protocols and that all future EOC Gynecologic
      Cancer InterGroup trials should adhere to these.

PMID- 28448858
TI  - The Development and piloting of an eHealth breastfeeding resource targeting
      fathers and partners as co-parents.
AB  - OBJECTIVE: Traditionally breastfeeding education programs target mothers solely.
      The objective of this study was to design and pilot test an interactive eHealth
      breastfeeding co-parenting resource developed to target both mothers and fathers.
      eHealth resources provide an accessible and engaging format on which to educate
      parents and assist them in meeting their breastfeeding goals. Best practices to
      design such resources are not currently known. DESIGN: A three phase pilot study
      was conducted. The three phases included conducting a needs assessment, creating
      the resource and pilot testing the resource with mother, father and health care
      professionals to determine their perspectives regarding the usability and design
      of the prototype resource. The interactive prototype resource was designed to
      provide information to parents on breastfeeding and co-parenting, which included
      suggestions on how fathers can be involved and support breastfeeding and how the
      couples can work as a team to meet their breastfeeding goals. Setting:
      Recruitment took place in a health region in Southern Ontario, Canada between
      June 2014 and March 2015. Online questionnaires were completed by participants in
      all phases of the study. PARTICIPANTS: Participants (n=149) were pregnant or new
      mothers and their partners in the health region who read and speak English and
      had access to the internet and health care professionals who work with
      breastfeeding families in Ontario, Canada. INTERVENTION: A prototype eHealth
      breastfeeding co-parenting resource was developed based on maternal and paternal
      feedback from Phase I and utilized an interactive interface which included games
      and multimodal information delivery. The prototype eHealth resource was provided
      to the parents in Phase II and health care professionals in Phase III. The final
      resource was created based on feedback from these participants. MEASUREMENTS AND
      FINDINGS: The resource was pilot tested with new and expectant parents using pre-
      and post-test questionnaires which included measures for breastfeeding self
      efficacy (Breastfeeding Self-Efficacy Short Form), infant feeding attitude (Iowa
      Infant Feeding Attitude Scale), breastfeeding knowledge (Breastfeeding Knowledge
      Questionnaire) and co-parenting relationship (Co-parenting Relationship Scale).
      Maternal and paternal breastfeeding self-efficacy and knowledge and infant
      feeding attitude scores all increased from pre-test to post-test. However, there
      was no difference in the co-parenting relationship scores from pretest to post
      test. KEY CONCLUSIONS: This study has used feedback from parents and health
      professionals to develop a prototype resource which appears to be effective in
      increasing parents' breastfeeding knowledge, attitude and self-efficacy. The
      prototype resource was rated positively by parents and health care providers.
      IMPLICATIONS FOR PRACTICE: An eHealth breastfeeding co-parenting resource
      designed with input from the target population is an effective way of providing
      information to mothers and fathers. Further research with a randomized controlled
      design and more diverse populations is needed to determine effectiveness of the
      resource on breastfeeding duration and exclusivity.

PMID- 28448859
TI  - Evolution of the methodological quality of controlled clinical trials for
      myofascial trigger point treatments for the period 1978-2015: A systematic
      review.
AB  - BACKGROUND: The methodological quality of controlled clinical trials (CCTs) of
      physiotherapeutic treatment modalities for myofascial trigger points (MTrP) has
      not been investigated yet. OBJECTIVES: To detect the methodological quality of
      CCTs for physiotherapy treatments of MTrPs and demonstrating the possible
      increase over time. DESIGN: Systematic review. METHODS: A systematic search was
      conducted in two databases, Physiotherapy Evidence Database (PEDro) and Medicine
      Medical Literature Analysis and Retrieval System online (MEDLINE), using the same
      keywords and selection procedure corresponding to pre-defined inclusion criteria.
      The methodological quality, assessed by the 11-item PEDro scale, served as
      outcome measure. The CCTs had to compare at least two interventions, where one
      intervention had to lay within the scope of physiotherapy. Participants had to be
      diagnosed with myofascial pain syndrome or trigger points (active or latent).
      RESULTS: A total of n = 230 studies was analysed. The cervico-thoracic region was
      the most frequently treated body part (n = 143). Electrophysical agent
      applications was the most frequent intervention. The average methodological
      quality reached 5.5 on the PEDro scale. A total of n = 6 studies scored the value
      of 9. The average PEDro score increased by 0.7 points per decade between 1978 and
      2015. CONCLUSIONS: The average PEDro score of CCTs for MTrP treatments does not
      reach the cut-off of 6 proposed for moderate to high methodological quality.
      Nevertheless, a promising trend towards an increase of the average methodological
      quality of CCTs for MTrPs was recorded. More high-quality CCT studies with
      thorough research procedures are recommended to enhance methodological quality.

PMID- 28448860
TI  - A unique presentation of renal cell transformation into renal cell carcinoma in
      subcutaneous fatty tissue post twenty year old healing gun-shot wound: A case
      report.
AB  - INTRODUCTION: Renal cell carcinoma (RCC) is the most common malignancy in the
      genitourinary tract, and is among the 10 most common cancers in both males and
      females. PRESENTATION OF CASE: We report a case of a 61-year-old male who
      presented with a cutaneous lesion on his left back side at a site where he had
      undergone several surgeries - including Left nephrectomy - twenty years ago for a
      gun-shot wound he sustained which penetrated his abdomen. DISCUSSION: At that
      time pathology reports turned out to be normal, specially left kidney pathology
      report which was negative for any malignancy. Twenty years later, patient
      presented with a clear fluctuating painless cutaneous mass of 1-2cm on his left
      back side, which grew gradually over time. Histopathologically, the incisional
      biopsy showed trabecular & papillary clear cells with prominent vascularity and
      hemosiderin deposition in the stroma, consistent with a malignant Renal cell
      Carcinoma (RCC). Immunohistochemically, it stained positive for Vimentin, CD10,
      PAX-8. Labs revealed positive renal cell carcinoma antibody. CT scans, urine
      tests, and bone scans failed to reveal the site of the primary lesion.
      Furthermore, the patient reports minimal constitutional symptoms and is grossly
      well. CONCLUSION: The authors have reported an interesting case of an RCC
      presenting in a healed gun-shot wound in a previously nephrectomized patient. To
      the best of authors' knowledge, such a case hasn't been reported in the
      literature before, with it being unique in its time course, preceding events, and
      absence of primary lesions.

PMID- 28448861
TI  - Congenital unilateral diaphragmatic eventration in an adult: A rare case
      presentation.
AB  - We present a rare case of 32year old female with congenital diaphragmatic
      eventeration female presenting in an adult. She had symptoms of intermittent
      dyspnea and occasional epigastric discomfort. Patient had no previous history of
      trauma. Physical examination showed bowel sound involving the left hemithorax.
      Imaging modalities confirmed the diagnosis of a congenital left diaphragmatic
      eventeration. Patient underwent plication of the diaphragm using the abdominal
      approach. Intra-operatively, the left diaphragm was attenuated. Plication was
      done with 1st layer of imbricating silk heavy sutures buttressed by a second
      layer of interrupted absorbable sutures. She post-operatively had atelectasis on
      the left lung. Incentive spirometry and deep breathing exercises were started
      with resolution of the atelectasis after 1 week post-operatively. Patient had an
      unremarkable post-operative stay with resolution of symptoms. There are reports
      that diaphragmatic eventration diagnosed even as late 70 years old, highlighting
      the dogma that this is an asymptomatic disorder does not need all the time
      surgical therapy. But we still recommend surgical therapy as soon as diagnosis is
      confirmed. In this patient, there was no recurrence of symptoms after a follow-up
      of 2 years. Whether surgery indeed improved lung functions in these vastly
      asymptomatic patients, these questions could be an active area of research in the
      long term outcomes of these patients.

PMID- 28448862
TI  - The first case report of failed single-anastomosis-duodeno-ileal bypass converted
      to One anastomosis gastric bypass/Mini-gastric bypass.
AB  - INTRODUCTION: The established single-anastomosis-duodeno-ileal bypass with sleeve
      gastrectomy (SADI-S) is based on a sleeve gastrectomy (SG) as the restrictive
      part of the procedure. Due to preserved pylorus, SG has the disadvantage of a
      high-pressure system with de novo or worsening of existing gastroesophageal
      reflux disease (GERD). CASE PRESENTATION: A female patient presented herself due
      to protracted GERD and weight regain after multiple bariatric surgeries. At an
      initial weight of 158kg (BMI 62.5kg/m2) the patient underwent adjustable gastric
      banding in 2009. After band removal in slippage, the patient underwent SG at a
      weight of 135kg in 2012. Nine months after SG, SADI-S was performed as a
      malabsorptive second step procedure. After 32 months the patient suffered from
      severe GERD under proton pump inhibitor therapy. Actual weight was 107.9kg (BMI
      42.7kg/m2). Upper endoscopy showed a hiatal hernia and esophagitis B and dorsal
      hiatoplasty was performed. After 6 months in still existing severe GERD and
      weight regain indication for laparoscopic conversion to One anastomosis gastric
      bypass/Mini-gastric bypass (OAGB/MGB) was given, aiming to reduce the high
      pressure system of SG in a low-pressure system of OAGB/MGB. One year after
      revisional surgery reflux was reported to be only occasionally. Further weight
      loss was seen (91kg, BMI 36kg/m2, EWL 67.7%). CONCLUSION: SG as the restrictive
      part of SADI-S may lead to GERD and consequently to pathologic eating of "soft"
      calories, that defeats the operation and results in weight regain. OAGB/MGB might
      be a simple method to rescue such failed SADI-S patients.

PMID- 28448863
TI  - Multi-sited hydatid cystic disease with muscular involvement in a young female: A
      case report from Syria.
AB  - INTRODUCTION: Hydatidosis is a unique disease caused by a tapeworm called
      Echinococcus granulosus. Musculoskeletal involvement with hydatid cystic disease
      accounts for less than 5% of all cases. The main purpose of this study is to
      present a case of multi-sited hydatid cystic disease and how to manage it.
      PRESENTATION OF CASE: Here we present a case of 14-year-old girl complained of a
      gradually enlarging mass on her left shoulder with a final diagnosis of triple
      sited hydatid cystic disease including the right lung, the left trapezius muscle
      and the liver. DISCUSSION: The diagnosis was made by non invasive radiological
      procedures (CT scan and MRI). The management consisted of aspiration and
      reinjection of hypertonic solution to the lung cyst followed by complete surgical
      resection, enucleation of the muscular lesion and conservative management of the
      liver lesion. After Three months of follow up there was no recurrence at the
      sites of operation and the liver cyst reduced in size. CONCLUSION: Multi-sited
      hydatid cysts could be treated through one stage surgery followed by chemotherapy
      with benzimidazoles.

PMID- 28448864
TI  - New agents for endocrine resistance in breast cancer.
AB  - Estrogen receptor positive (ER+) and HER2-negative (HER2-) breast cancer (BC) is
      the most common BC subtype, defined by expression of the ER and absence of HER2
      amplification. Endocrine treatment (ET), aiming at therapeutic blockade of ER
      signaling, represents the therapeutic mainstay for patients with both early and
      advanced disease. Despite its wide therapeutic efficacy, ET fails for a
      proportion of ER+, HER2- BC patients with early disease who develop endocrine
      resistance, resulting in disease recurrence. Endocrine resistance occurs almost
      invariably in patients with metastatic disease. Recently, increasing
      understanding of the molecular mediators of endocrine resistance has been
      achieved. This review focuses on the molecular mechanisms mediating endocrine
      resistance, on molecularly targeted agents to overcome or delay it, and potential
      predictive biomarkers for accurate patient stratification.

PMID- 28448865
TI  - Glycolipids from spinach suppress LPS-induced vascular inflammation through eNOS
      and NK-kappaB signaling.
AB  - Glycolipids are the major constituent of the thylakoid membrane of higher plants
      and have a variety of biological and pharmacological activities. However, anti
      inflammatory effects of glycolipids on vascular endothelial cells have not been
      elucidated. Here, we investigated the effect of glycolipids extracted from
      spinach on lipopolysaccharides (LPS)-induced endothelial inflammation and
      evaluated the underlying molecular mechanisms. Treatment with glycolipids from
      spinach had no cytotoxic effects on cultured human umbilical vein endothelial
      cells (HUVECs) and significantly blocked the expression of LPS-induced
      interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), vascular cell
      adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) in
      them. Glycolipids treatment also effectively suppressed monocyte adhesion to
      HUVECs. Treatment with glycolipids inhibited LPS-induced NF-kappaB
      phosphorylation and nuclear translocation. In addition, glycolipids treatment
      significantly promoted endothelial nitric oxide synthase (eNOS) activation and
      nitric oxide (NO) production in HUVECs. Furthermore, glycolipids treatment
      blocked LPS-induced inducible NOS (iNOS) expression in HUVECs. Pretreatment with
      a NOS inhibitor attenuated glycolipids-induced suppression of NF-kappaB
      activation and adhesion molecule expression, and abolished the glycolipids
      mediated suppression of monocyte adhesion to HUVECs. These results indicate that
      glycolipids suppress LPS-induced vascular inflammation through attenuation of the
      NF-kappaB pathway by increasing NO production in endothelial cells. These
      findings suggest that glycolipids from spinach may have a potential therapeutic
      use for inflammatory vascular diseases.

PMID- 28448866
TI  - Function of microRNA-143 in different signal pathways in cancer: New insights
      into cancer therapy.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post
      transcriptional regulation of gene expression. They play important roles in
      cellular events such as growth and differentiation. Deregulation of miRNAs is
      frequently evident in human cancers where their aberrant expression is associated
      with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage
      response. The miRNAs are important in cancer as ~50% of miRNA genes are located
      in cancer-associated regions such as fragile sites of genome. MiRNA-143 is
      defined as an important tumor suppressor in a variety of neoplasms including
      solid tumors and B-cell malignancies. MiRNA-143 is involved in the pathogenesis
      of cancers by directly targeting several mRNAs such as Bcl-2, KRAS, HK2, DNMT3A,
      TP53 and MMP-13. In this study, an overview of the miRNA-143 function in
      different signaling pathways in cancer will be provided.

PMID- 28448867
TI  - Immuno-modulatory and cellular antioxidant activities of kappa-selenocarrageenan
      in combination with Epirubicin in H22 hepatoma-bearing mice.
AB  - BACKGROUND: Human hepatocellular carcinoma (HCC) has a high rate of tumor
      recurrence and metastasis, resulting in shortened survival time. The aim of this
      study is to evaluate the synergistic anti-tumor effects and underlying mechanism
      of kappa-selenocarrageenan (KSC) in combination with the chemotherapy drug
      epirubicin (EPI) in H22 tumor-bearing mice. METHODS: Hepatocellular carcinoma H22
      cells were implanted into mice. After the transplants were successfully
      established, the animals were divided into four groups: namely the control group,
      the KSC group, the EPI group and the KSC+EPI group. The effects of KSC and EPI on
      tumor growth, survival time, thymus index, spleen index, white blood cells (WBC),
      splenocyte proliferation, natural killer (NK) cell activity, serum TNF-alpha and
      IL-2 levels, and antioxidant enzymes in the liver cells were determined. RESULTS:
      KSC and/or EPI significantly reduced tumor weight and prolonged the survival
      time. Furthermore, KSC could attenuate EPI-induced atrophy in the thymus and
      spleen, as well as other toxicities, which may indicate an additive effect of
      this combination against organ dysfunction and cellular injury. KSC significantly
      promoted Con A- and LPS-stimulated splenocyte proliferation, enhanced NK cell
      activity, and reversed the inhibition of NK activity induced by EPI (P<0.01). In
      addition, KSC could elevate serum TNF-alpha and IL-2 levels, increase the GSH-Px,
      SOD, CAT and GSH activity levels in liver tissue, and reduce MDA content.
      CONCLUSIONS: These results suggest that KSC can regulate immune function in mice
      and suppress the growth of tumor in H22 tumor-bearing mice, and its synergistic
      antitumor activity with epirubicin may be related to its antioxidant and immuno
      modulatory effects.

PMID- 28448868
TI  - Protective effects of Teucrium polium aqueous extract and ascorbic acid on
      hematological and some biochemical parameters against carbon tetrachloride (CCl4)
      induced toxicity in rats.
AB  - Herbal drugs play a crucial function to protect organisms from the toxic effect
      of some compounds. The present study was designed to evaluate the protective
      effects of Teucrium Polium (TP) aqueous extract and vitamin C (Vit C) against
      carbon tetrachloride (CCl4) which induced toxicity in rats. Male albino Wistar
      rats were divided into six groups: group I was used as controls, group II
      received CCl4 in olive oil (0.5ml/kg) by gavage, and group III received CCl4 in
      olive oil (0.5ml/kg) by gavage after three days of receiving TP (5g/l), orally,
      for seven days; Group IV received TP (5g/l) alone, orally, for seven days, Group
      V received CCl4 in olive oil (0.5ml/kg) by gavage after three days of receiving
      Vit C (250mg/kg) by intramuscular injection and Group VI received Vit C
      (250mg/kg) alone by intramuscular injection, for day seven. Some biochemical and
      hematological parameters were investigated. Our results showed that the
      administration of CCl4 caused hepatotoxicity as monitored by the significant
      increase in the levels of hepatic markers enzymes (lactate dehydrogenase (LDH),
      Alkaline phosphatase (PAL), total bilirubin (TB) and Gamma glutamyl transferase
      (gammaGT) levels) and a decrease in hematological parameters such as white blood
      cell (WBC), red blood cell count (RBC), mean corpuscular hemoglobin concentration
      (MCHC) and blood platelet count (PLT). Treatment with TP or Vit C appeared to be
      effective against hematotoxic and the liver changes induced by CCl4, as evidenced
      by the improvement of the parameters cited above. The CCl4-treated group
      demonstrated a significant increase of malondialdehyde (MDA) levels in
      erythrocytes thus causing a reduction in antioxidant defense system. Pretreatment
      with TP or Vit C improved the biochemical analyses, hematological parameters, and
      antioxidant defense system.

PMID- 28448869
TI  - Immunomodulatory activities of phlorizin metabolites in lipopolysaccharide
      stimulated RAW264.7 cells.
AB  - The immunomodulatory effects of two new phlorizin metabolites, phloretin 4-O-beta
      d-glucuronide (1), 6-methoxyl-phloretin-2-O-beta-d-glucuronide (2), together with
      phloretin-2-O-beta-d-glucuronide (3) on lipopolysaccharide (LPS)-stimulated RAW
      264.7 macrophage cells were determined. 1-3 (1-5MUg/ml) significantly inhibited
      the production of NO (p<0.01). At the concentration of 5MUg/ml, 2 and 3 further
      inhibited iNOS mRNA expression (p<0.01 or 0.05), and 1-3 inhibited iNOS protein
      expression (p<0.01). Conversely, they all promoted the proinflammatory cytokine
      TNF-alpha mRNA expression (p<0.01). For IL-10 mRNA, 1 and 3, which are main
      metabolism forms in rat plasma, obviously promoted its expression (p<0.01), while
      metabolite 2, which was only detected in rat urine, showed inhibitory activity,
      but 1-3 alone without LPS stimulation had no effect on the expression of both TNF
      alpha and IL-10 mRNA expression. 1 further inhibited VEGF, CCL2 and CXCL1 mRNA
      expression at the concentration of 5-25MUg/ml (p<0.01). These results indicated
      phloretin's metabolites with different structural forms showed different
      immunomodulatory activities.

PMID- 28448870
TI  - Knockdown of MSP58 inhibits the proliferation and metastasis in human renal cell
      carcinoma cells.
AB  - The 58-kDa microspherule protein (MSP58) has been reported to play an important
      role in the tumorigenesis and progression of cancers. However, little is known
      about the role of MSP58 in human renal cell carcinoma (RCC). In this study, we
      investigated the expression and biological roles of MSP58 in RCC. The results
      indicated that the expressions of MSP58 at both mRNA and protein levels were
      greatly up-regulated in human RCC tissues and cell lines. Down-regulation of
      MSP58 significantly suppressed the proliferation, migration/invasion of RCC
      cells, as well as attenuated tumor growth in a 786-O xenograft model in vivo.
      Mechanistically, knockdown of MSP58 expression sharply down-regulated the protein
      expression levels of beta-catenin, c-myc and cyclin D1 in 786-O cells. Taken
      together, these findings showed that MSP58 downregulation suppressed the
      proliferation and invasion of RCC cells, at least in part, through regulating the
      Wnt/beta-catenin signaling pathway. Thus, MSP58 may act as a novel therapeutic
      target for the treatment of RCC.

PMID- 28448871
TI  - Immunomodulatory effects of stem cells: Therapeutic option for neurodegenerative
      disorders.
AB  - Stem cells have the capability of self-renewal and can differentiate into
      different cell types that might be used in regenerative medicine.
      Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease
      (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently
      lack effective treatments. Although stem cell therapy is still on the way from
      bench to bedside, we consider that it might provide new hope for patients
      suffering with neurodegenerative diseases. In this article, we will give an
      overview of recent studies on the potential therapeutic use of mesenchymal stem
      cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced
      pluripotent stem cells (iPSCs), and perinatal stem cells to neurodegenerative
      disorders and we will describe their immunomodulatory mechanisms of action in
      specific therapeutic modalities.

PMID- 28448872
TI  - Curcumin attenuates lipopolysaccharide/d-galactosamine-induced acute liver injury
      by activating Nrf2 nuclear translocation and inhibiting NF-kB activation.
AB  - Curcumin, a polyphenol in curry spice isolated from the rhizome of turmeric, has
      been reported to possess versatile biological properties including anti
      inflammatory, anti-oxidant, antifibrotic, and anticancer activities. In this
      study, the hepatoprotective effect of curcumin was investigated in
      lipopolysaccharide (LPS)/d-galactosamine (d-GalN)-induced acute liver injury
      (ALI) in rats. Experimental ALI was induced with an intraperitoneal (ip)
      injection of sterile 0.9% sodium chloride (NaCl) solution containing 8MUg LPS and
      800mg/kg d-GalN. Curcumin was administered once daily starting three days prior
      to LPS/d-GalN treatment. Results indicated that curcumin could attenuate hepatic
      pathological damage, decrease serum ALT and AST levels, and reduce
      malondialdehyde (MDA) content in experimental ALI rats. Moreover, higher dosages
      of curcumin pretreatment inhibited NF-kappaB activation and reduced serum TNF
      alpha and liver TNF-alpha levels induced by LPS/d-GalN ip injection. Furthermore,
      we found that curcumin up-regulated the expression of nuclear Nrf2 and Nrf2
      dependent antioxidant defense genes including heme oxygenase-1 (HO-1), glutamate
      cysteine ligase (GCLC), NAD(P)H dehydrogenase, and quinone (NQO-1) in a dose
      dependent manner. Our results showed that curcumin protected experimental animals
      against LPS/d-GalN-induced ALI through activation of Nrf2 nuclear translocation
      and inhibition of NF-kappaB activation.

PMID- 28448873
TI  - Osthole attenuates lipid accumulation, regulates the expression of inflammatory
      mediators, and increases antioxidants in FL83B cells.
AB  - Osthole is found in Cnidium monnieri (L.) and has anti-inflammatory and anti
      oxidative properties. It also inhibits the proliferation of hepatocellular
      carcinoma cells. This study aimed to evaluate the osthole suppressive
      nonalcoholic fatty liver disease effects in oleic acid (OA)-induced hepatic
      steatosis and if it can modulate inflammatory responses and oxidative stress.
      FL83B cells were pretreated with OA (250MUMU) for 24h, and then added different
      concentrations of osthole (3-100MUM) for 24h. Subsequently, lipolysis and
      transcription factors of adipogenesis and phosphorylation of AMP-activated
      protein kinase proteins were measured. In addition, cells with OA-induced
      steatosis were H2O2-stimulated, and then incubated with osthole to evaluated if
      it could suppress its progression to steatohepatitis. Osthole significantly
      enhanced glycerol release and lipolysis protein expression. Osthole also promoted
      phosphorylation of AMP-activated protein kinases and increased the activity of
      triglyceride lipase and hormone- sensitive lipase. Osthole suppressed the nuclear
      transcription factor kappa-B and the p38 mitogen-activated protein kinase
      pathway, and decreased the malondialdehyde concentration in FL83B cells with OA
      induced steatosis that were treated with H2O2. These results suggest that osthole
      might suppress nonalcoholic fatty liver disease by decreasing lipid accumulation,
      and through its anti-oxidative and anti-inflammatory effects via blocked NF
      kappaB and MAPK signaling pathways.

PMID- 28448874
TI  - Regulation and roles of CD26/DPPIV in hematopoiesis and diseases.
AB  - Dipeptidyl peptidase IV (DPPIV),1 on the surface of certain cells, where it is
      also referred to as CD26, is involved in a vast majority of biological and
      pathological processes. CD26/DPPIV function contributes to cancer and tumor
      metastasis as well as inhibition of its expression which alters the expression of
      immune response-related genes. CD26/DPPIV is a widely distributed multifunctional
      integral membrane and secreted protein that is defined as early predictive
      biomarker in HIV, cancer and autoimmunity diseases like diabetes and multiple
      sclerosis. CD26/DPPIV-chemokine interaction may have a functional role in T-cells
      and overall immune function. It is expressed at low density on resting T cells,
      but is upregulated with T cell activation. In this review, we summarize valuable
      information about detailed biological aspects and pharmacokinetic characteristics
      of CD26/DPPIV and its clinical efficacy, focusing particularly on the role of
      CD26/DPPIV in immunological and non-immunological diseases. We also describe our
      recent work about umbilical cord blood (UCB)2 hematopoietic stem cell
      transplantation strategies in which identified CD26+ cells can be differentiated
      to immune cells under certain culture condition.

PMID- 28448875
TI  - Bioengineered mannan sulphate capped silver nanoparticles for accelerated and
      targeted wound healing: Physicochemical and biological investigations.
AB  - In the present study, surface functionalized mannan sulphate silver nanoparticles
      (MS-AgNPs) were prepared and assessed for their wound healing potential. 20nm
      sized, spherical MS-AgNPs were prepared by one pot synthesis approach wherein the
      sulphated polysaccharide mannan sulphate (MS) played dual role of reducing as
      well as capping agent. The crystalline MS-AgNPs exhibited surface plasmon
      resonance centered at 400nm along with -32.40mV zeta potential. These stable MS
      AgNPs showed enhanced cytocompatibility, targeting potential and cellular uptake
      in murine macrophages, human skin fibroblasts and human keratinocytes as compared
      to citrate reduced silver nanoparticles (C-AgNPs). In the in vivo excision and
      incision wound models, MS-AgNPs as hydrogel formulations indicated better
      efficacy than the conventional and marketed silver formulations. Thus, the
      synthesized MS-AgNPs depicted a promising potential for site-specific topical
      delivery in accelerated wound therapy.

PMID- 28448876
TI  - Study on electronic properties, thermodynamic and kinetic parameters of the
      selected platinum(II) derivatives interacting with guanine.
AB  - Interaction of hydrated forms of several potential anticancer agents
      (PtCl2(diaminocyclohexane), trans-[PtCl2(NH3)(thiazole)], cis
      [PtCl2(NH3)(piperidine)], and cis-PtCl2(NH3)(cyclohexylamine) complexes) with
      guanine are explored and compared with an analogous interaction of cisplatin.
      Basic electronic properties, binding and stabilization energies are determined
      and energy profiles for the aquation reaction are estimated at the B3LYP/6
      311++G(2df,2pd) level of theory. It is found that the substitution reaction is an
      exothermic and exergonic process with DeltaG slightly less negative than 
      20kcal/mol. The largest energy release occurs for PtCl(H2O)(diaminocyclohexane)
      complex. The rate constants for the Pt(II) complexes in the chloro- and hydroxo
      form are compared and an impact of the ligand in the trans position to water is
      discussed.

PMID- 28448877
TI  - Synthesis, structure and cytotoxicity of a series of Dioxidomolybdenum(VI)
      complexes featuring Salan ligands.
AB  - Seven hexacoordinated cis-dioxidomolybdenum(VI) complexes [MoO2L1-7] (1-7)
      derived from various tetradentate diamino bis(phenolato) "salan" ligands, N,N'
      dimethyl-N,N'-bis-(2-hydroxy-3-X-5-Y-6-Z-benzyl)-1,2-diaminoethane {(X=Br, Y=Me,
      Z=H (H2L1); X=Me, YCl, Z=H (H2L2); X=iPr, Y=Cl, Z=Me (H2L3)} and N,N'-bis-(2
      hydroxy-3-X-5-Y-6-Z-benzyl)-1,2-diaminopropane {(X=Y=tBu, Z=H (H2L4); X=Y=Me, Z=H
      (H2L5); X=iPr, YCl, Z=Me (H2L6); X=Y=Br, Z=H (H2L7)} containing O-N donor atoms,
      have been isolated and structurally characterized. The formation of cis
      dioxidomolybdenum(VI) complexes was confirmed by elemental analysis, IR, UV-vis
      and NMR spectroscopy, ESI-MS and cyclic voltammetry. X-ray crystallography showed
      the O2N2 donor set to define an octahedral geometry in each case. The complexes
      (1-7) were tested for their in vitro antiproliferative activity against HT-29 and
      HeLa cancer cell line. IC50 values of the complexes in HT-29 follow the order
      6<7<<1<2<5<<3<4 while the order was 6<7<5<1<<3<4<2 in HeLa cells. Some of the
      complexes proved to be as active as the clinical referred drugs, and the greater
      potency of 6 and 7 (IC50 values of 6 are 2.62 and 10.74MUM and that of 7 is 11.79
      and 30.48MUM in HT-29 and HeLa cells, respectively) may be dependent on the
      substituents in the salan ligand environment coordinated to the metal.

PMID- 28448878
TI  - Rapid extraction of uranium from sea water using Fe3O4 and humic acid coated
      Fe3O4 nanoparticles.
AB  - Uranium is one of the most toxic elements present in the environment and a number
      of methods have been developed for its extraction. Herein we have demonstrated a
      new method using magnetic nanoparticles (NPs) that can be used for uranium
      extraction from water and sea water matrix. Fe3O4 and humic acid (HA) coated
      Fe3O4 NPs with different amount of HA coating were synthesized and uranium
      sorption from water and sea water matrix was demonstrated. It was observed that
      sorption increases with increase in amount of HA coating. NPs settlement in
      presence of magnetic field was monitored where only bare Fe3O4 and Fe3O4/HA 1 NPs
      settles while no settlement was observed for Fe3O4/HA 2 and Fe3O4/HA 3 NPs.
      Considering both sorption and particle separation from the matrix Fe3O4/HA 1 NPs
      are the best among synthesized ones with maximum sorption capacity of 10.5mg of
      U/g of NPs. The results presented here reveal the exceptional potential of
      magnetic NPs and functionalized magnetic NPs for environmental remediation of
      uranium and to extract uranium from sea water on which to the best of our
      knowledge no report is available till now.

PMID- 28448879
TI  - Adsorption of organic arsenic acids from water over functionalized metal-organic
      frameworks.
AB  - Organic arsenic acids (OAAs) are regarded as water pollutants because of their
      toxicity and considerable solubility in water. Adsorption of OAAs such as
      phenylarsonic acid (PAA) and p-arsanilic acid (ASA) from water was investigated
      over functionalized (with OH groups) metal-organic framework (MOF, MIL-101), as
      well as over pristine MIL-101 and commercial activated carbon. The highly porous
      MIL-101 bearing three hydroxyl groups (MIL-101(OH)3) exhibited remarkable PAA and
      ASA adsorption capacities. Based on the effects of pH on PAA and ASA adsorption,
      hydrogen bonding was suggested as a plausible mechanism of OAA adsorption.
      Importantly, OAAs and MIL-101(OH)3 can be viewed as hydrogen-bond acceptors and
      donors, respectively. Moreover, MIL-101(OH)3 could be regenerated by acidic
      ethanol treatment, being a promising adsorbent for the removal of PAA and ASA
      from water.

PMID- 28448880
TI  - Rapid green synthesis of gold nanocatalyst for high-efficiency degradation of
      quinclorac.
AB  - Porous chemical pretreated Saccharomyces cerevisiae was used as support,
      stabilizer, and reducing agent for the rapid green synthesis of gold
      nanocatalyst. Au nanoparticles (Au NPs) were generated through in-situ reduction
      of the absorbed Au(III) by the reductive functional groups of mannoproteins in
      yeast cell wall. The obtained spherical mono-dispersed Au NPs have an average
      particle diameter of 9.99+/-1.63nm as evidenced by TEM image, and exhibits
      excellent catalytic activity for the dechlorination of quinclorac to 8-quinoline
      carboxylic acid by sodium borohydride. The reductive dechlorination of quinclorac
      is chemical reaction controlled and follows pseudo-first-order kinetic model. The
      rate constant increases with the increase of the temperature and decrease of the
      initial quinclorac concentration. The present synthesis protocol of Au
      nanocatalyst has the advantages of rapid, convenient and mild operation, high
      catalytic dechlorination efficiency and organic solvent-free nature.

PMID- 28448881
TI  - Social capital and cigarette smoking: New empirics featuring the Norwegian HUNT
      data.
AB  - Using a rich Norwegian longitudinal data set, this study explores the effects of
      different social capital variables on the probability of cigarette smoking. There
      are four social capital variables available in two waves of our data set. Our
      results based on probit (and OLS) analyses (with municipality fixed-effects) show
      that the likelihood of smoking participation is negatively and significantly
      associated with social capital attributes, namely, community trust (-0.017),
      participation in organizational activities (-0.032), and cohabitation (-0.045).
      Significant negative associations were also observed in panel data, pooled OLS,
      and random effects models for community trust (-0.024; -0.010) and cohabitation (
      0.040; -0.032). Fixed-effects models also showed significant negative effects for
      cohabitation (-0.018). Estimates of alternative instrumental variables (IV) based
      on recursive bivariate probit and IV-GMM models also confirmed negative and
      significant effects for three of its characteristics: cohabitation (-0.030; 
      0.046), community trust (-0.065; -0.075), and participation in organizational
      activities (-0.035; -0.046). The limitations of our conclusions are discussed,
      and the significance of our study for the field of social capital and health is
      described, along with suggested avenues for future research.

PMID- 28448883
TI  - Exploring the attitudes, knowledge and beliefs of nurses and midwives of the
      healthcare needs of the LGBTQ population: An integrative review.
AB  - OBJECTIVES: To explore current literature surrounding the knowledge, beliefs and
      attitudes of nurses and midwives of the healthcare needs of Lesbian, Gay,
      Bisexual, Transgender and Queer (LGBTQ) patients and their influence on equal and
      non-discriminatory care for LGBTQ individuals. DESIGN: Systematic integrative
      review. DATA SOURCES: CINAHL, MEDLINE, PubMed, InterNurse. REVIEW METHODS: This
      integrative review used Wakefield's (2014) framework to establish the knowledge,
      beliefs and attitudes of nurses and midwives of the healthcare needs of LGBTQ
      patients. Qualitative, quantitative and mixed methods primary studies carried out
      between 2006 and 2015 from 7 countries were included. Four databases were
      searched and 98 studies were screened for eligibility by two researchers. Level
      of evidence was assessed by the Scottish Intercollegiate Guidelines Network
      (SIGN, 2010) criteria and quality was assessed by a screening tool adapted from
      Noyes and Popay (2007) for qualitative papers and Quality Assessment Tool for
      Quantitative Studies adapted from the Effective Public Health Practice Project
      (EPHPP, 2010). Following PRISMA guidelines, this integrative review analysed and
      synthesised evidence using thematic analysis to generate themes. RESULTS: 24
      papers were included in the final synthesis which revealed four primary themes:
      Heteronormativity across Healthcare; Queerphobia; Rainbow of Attitudes; Learning
      Diversity. CONCLUSIONS: Nurses and midwives possess a wide spectrum of attitudes,
      knowledge and beliefs which impact the care received by LGBTQ patients. Many
      issues of inadequate care appear to be due to a culture of heteronormativity and
      a lack of education on LGBTQ health. Further research is needed on interventions
      which could facilitate disclosure of sexual orientation and interrupt
      heteronormative assumptions by staff. It is recommended that LGBTQ issues be
      included within undergraduate nursing and midwifery education or as part of
      continued professional development.

PMID- 28448882
TI  - Baccalaureate Student Nurses' Study Habits Prior to Admission to Nursing Program:
      A Descriptive Qualitative Study.
AB  - BACKGROUND: Faculty continue to observe students struggling as they adapt their
      study strategies to learn nursing core content. OBJECTIVES: This study described
      the study habits of Bachelor of Science in Nursing (BSN) students prior to
      admission to the program. DESIGN: This study used a descriptive qualitative
      research design. SETTINGS AND PARTICIPANTS: A purposive sample of 19 BSN students
      (juniors [n=10] and seniors [n=9]) from a 4-year public Midwestern university
      were included in this study. METHODS: Two focus group sessions, using a semi
      structured interview guide, were conducted in the spring semester of 2013.
      RESULTS: The four themes which emerged from the analysis of data were: "I just
      got it," "I had a lot of time then," "I studied alone" mostly, and "...a little
      struggle with the sciences." CONCLUSIONS: The findings suggest the BSN students
      did not study much or employed poor study strategies during their years
      completing general education courses. Academic support is needed by students
      prior to admission to the nursing program so they can learn effective study
      skills and modify their study habits for easier adaptation to the rigors of
      nursing education.

PMID- 28448884
TI  - Antiproliferative hydroxy-fatty acids from the fodder legume Stylosanthes
      guianensis.
AB  - Stylosanthes guianensis is a fodder legume native from South America and widely
      grown worldwide. Dried plant material was purchased on the web and taxonomically
      identified by light and SEM microscopy, and morphological analysis of plants
      germinated from seeds. The plant was extracted with dichloromethane:2-propanol
      (9:1). Bioguided fractionation using calcein-AM cytotoxicity assay on HeLa and
      A431 tumor cells allowed to isolate a lipophilic fraction, endowed with strong
      cytotoxicity. By means of 1- and 2-D NMR, HPLC-MS, and HR-ESIMS it could be seen
      that the fraction was an inseparable mixture of complex lipids, mainly consisting
      of esterified 3-hydroxy fatty acids. Acidic methanolysis of the mixture yielded 3
      OH C10 and C12 carboxylic acids, together with palmitic, stearic, and arachidonic
      acids. Mass values indicate the presence of dimeric and trimeric combinations of
      3-hydroxy, C10/C12 acids, and C16/C18/C20 acids, linked via ester bond. Monomeric
      hydroxyl-fatty acids were also observed, in particular derivatives of mono
      hydroxy and di-hydroxy linolenic, linoleic, and oleic acids. 3-O-acylated,
      esterified fatty acids are unusual in higher plants, and recall motifs of Gram
      negative endotoxin lipid A. These oxylipins are likely to be responsible for the
      antiproliferative activity of S. guianensis, suggesting possible use of the plant
      in the development of antitumor drugs.

PMID- 28448885
TI  - Development and validation of a liquid chromatographic method for the analysis of
      squaric acid dibutyl ester and its impurities.
AB  - A simple, fast and selective stability indicating liquid chromatographic method
      has been described for the simultaneous determination of squaric acid dibutyl
      ester and its impurities. The chromatographic separation was achieved on a C2
      column (250mm*4.6mm i.d., 5MUm) using a mobile phase consisting of 0.15%
      phosphoric acid - acetonitrile - methanol (30:60:10, v/v/v). Isocratic elution
      was performed at a flow rate of 1.0mLmin-1. The analytes were detected by UV at
      252nm. The method was validated according to the ICH guidelines and satisfactory
      results were obtained. The specificity of the developed method was tested using
      forced degradation solutions of the drug substance. Characterization of squaric
      acid dibutyl ester and its forced degradation products was achieved by coupling
      mass spectrometry (MS) to the liquid chromatographic (LC) system. The method was
      successfully applied for quality control purposes including assay and
      determination of related compounds as required by regulatory guidelines to ensure
      its safety and efficacy since no monograph is available in official compendia.

PMID- 28448886
TI  - New analytical method for determination of epimer metabolites in rat plasma after
      oral administration of Paeoniflorin by UPLC-TOF-MS following picolinoyl
      derivatization.
AB  - A highly sensitive analytical method was developed to study the in vivo
      metabolism of paeoniflorin, one of the most principal components in traditional
      Chinese medicine. After hydrolyzation with sulfatase, the epimer metabolites 7S
      paeonimetabolin I and 7R-paeonimetabolin I of paeoniflorin in rat plasma were
      successfully detected and well separated by LC-MS following picolinoyl
      derivatization for the first time. Borneol was used as the internal standard to
      quantify 7S-paeonimetabolin I and 7R-paeonimetabolin I in rat plasma. 7S
      paeonimetabolin I and 7R-paeonimetabolin I show similar but different
      pharmacokinetic behavior. 7S-paeonimetabolin I reached the maximum mean plasma
      concentration of 45.7+/-4.6ng/mL at about 1.5h after oral administration of
      paeoniflorin at a dose of 5mg/kg, while 7R-paeonimetabolin I reached the maximum
      mean plasma concentration of 39.2+/-3.5ng/mL at about 1.5h. The full metabolic
      pathway of paeoniflorin in rats was proposed. The monoterpene compound
      paeoniflorin was found to be metabolized to the sulfate of 7S-paeonimetabolin I
      and 7R-paeonimetabolin I in vivo which maybe responsible for the pharmacological
      effect of paeoniflorin.

PMID- 28448887
TI  - Macro-Raman spectroscopy for bulk composition and homogeneity analysis of multi
      component pharmaceutical powders.
AB  - A new macro-Raman system equipped with a motorized translational sample stage and
      low-frequency shift capabilities was developed for bulk composition and
      homogeneity analysis of multi-component pharmaceutical powders. Different
      sampling methods including single spot and scanning measurement were compared. It
      was found that increasing sample volumes significantly improved the precision of
      quantitative composition analysis, especially for poorly mixed powders. The multi
      pass cavity of the macro-Raman system increased effective sample volumes by 20
      times from the sample volume defined by the collection optics, i.e., from 0.02MUL
      to about 0.4MUL. A stochastic model simulating the random sampling process of
      polydisperse microparticles was used to predict the sampling errors for a
      specific sample volume. Comparison of fluticasone propionate mass fractions of
      the commercial products Flixotide(r) 250 and Seretide(r) 500 simulated for
      different sampling volumes with experimentally measured compositions verified
      that the effective sample volume of a single point macro-Raman measurement in the
      multi-pass cavity of this instrument was between 0.3MUL and 0.5MUL. The macro
      Raman system was also successfully used for blend uniformity analysis. It was
      concluded that demixing occurred in the binary mixture of l-leucine and d
      mannitol from the observation that the sampling errors indicated by the standard
      deviations of measured leucine mass fractions increased during mixing, and the
      standard deviation values were all larger than the theoretical lower limit
      determined by the simulation. Since sample volume was shown to have a significant
      impact on measured homogeneity characteristics, it was concluded that powder
      homogeneity analysis results, i.e., the mean of individual test results and
      absolute and relative standard deviations, must be presented together with the
      effective sample volumes of the applied testing techniques for any measurement of
      powder homogeneity to be fully meaningful.

PMID- 28448888
TI  - Isolation, identification and characterization of potential impurities of
      anidulafungin.
AB  - Eight impurities ranging from 0.03 to 0.97% in anidulafungin bulk drug were
      detected by HPLC. Four impurities (Imp-I, Imp-II, Imp-III and Imp-VIII) among
      impurities were isolated from the self-prepared or marketed samples of
      anidulafungin bulk drug by means of preparative HPLC. A thorough study was
      undertaken to characterize these impurities and based on 1D (1H, 13C, H-D, DEPT
      90 and 135) and 2D (COSY, TOCSY, HSQC, HMBC) NMR and ESI-MS spectral data. Based
      on the characterization data, Imp-I was found to be known open-chain hydrolysis
      product formed during the synthesis and degradation. Imp-II and Imp-III was
      lacked a methyl group at the C-4 and C-8 in anidulafungin, respectively, whereas
      Imp-VIII contained a methoxy group at the C-23. The latter three new impurities
      were identified as process-related substances.

PMID- 28448890
TI  - Metabolic profiles of neotuberostemonine and tuberostemonine in rats by high
      performance liquid chromatography/quadrupole time-of-flight mass spectrometry.
AB  - Neotuberostemonine (NS) and tuberostemonine (TS), a pair of stereoisomers, are
      the active components contained in Stemona tuberosa, an antitussive herbal
      medicine in China. Two isomers have different pharmacological efficacies, which
      will be related with their in vivo disposition. However, the metabolic fates of
      NS and TS remain unknown. A method of high performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry coupled with mass
      detect filter technique was established to investigate the metabolites in rat
      plasma, bile, urine, and feces after oral administration of the equal doses of NS
      and TS. The results showed that NS produced 48 phase I metabolites, including NS,
      3 hydrolyzed, 14 hydroxylated, 20 monohydrolyzed+hydroxylated and 10
      dihydrolyzed+hydroxylated metabolites. The number of detected NS metabolites was
      11, 39, 22 and 30 in plasma, bile, urine and feces. TS yielded 23 phase I
      metabolites, including TS, 3 hydrolyzed, 7 hydroxylated, 9
      monohydrolyzed+hydroxylated and 3 dihydrolyzed+hydroxylated metabolites. Besides,
      TS yielded 9 phase II metabolites, including 1 glucuronic acid and 2 glutathione
      conjugates, and the later further degraded and modified into cysteine-glycine,
      cysteine and N-acetylcysteine conjugates. The number of detected TS metabolites
      was 9, 24, 24 and 15 in plasma, bile, urine and feces. Different metabolic
      patterns may be one of the main reasons leading to different pharmacological
      effects of NS and TS.

PMID- 28448889
TI  - Studies on the metabolites difference of psoralen/isopsoralen in human and six
      mammalian liver microsomes in vitro by UHPLC-MS/MS.
AB  - Psoralen and isopsoralen are found in many fruits, vegetables and traditional
      Chinese medicines (TCM), such as Ficus carica L., Celery, Fructus Psoraleae etc.
      Modern pharmacological studies found that psoralen and isopsoralen can show
      estrogen-like activity, antitumor, and antibacterial activities etc. However,
      some research results also show some liver damage associated with the use of
      psoralen/isopsoralen or related medicines in human. Many studies focus on the
      pharmacological activities of psoralen/isopsoralen, while it is important to
      choose the suitable pharmacological models which are relevant to human in drug
      metabolism and pharmacokinetic process. The aim of this study is to identify the
      metabolites of psoralen/isopsoralen by human and six mammalian liver microsomes,
      and compare the metabolites difference of different species. Psoralen/isopsoralen
      are metabolized by liver microsomes of different animals to form five and seven
      metabolites, respectively. The metabolism of psoralen/isopsoralen undergoes
      hydroxylation, hydrogenation and hydrolysis, and oxidation of the furan ring to
      generate a furanoepoxide or gamma-ketoenal intermediate. Furanoepoxide then forms
      a dihydrodiol, while gamma-ketoenal forms 6-(7-hydroxycoumaryl)-acetic acid (in
      psoralen)/8-(7-hydroxycoumaryl)-acetic acid (in isopsoralen). By comparing the
      types of metabolites in the seven liver microsomes, it shows that the metabolic
      behaviors of psoralen by Beagle dog is most relevant to human, while the
      metabolic behaviors of isopsoralen by Sprague-Dawley rat is most similar to
      human. By comparing the relative amounts of the main metabolites, it shows that
      the metabolic capabilities of Sprague-Dawley rat and Rhesus monkey for psoralen
      are most similar to human, while the metabolic capabilities of Mouse, Dunkin
      Hartley guinea pig, Sprague-Dawley rat, and human for isopsoralen are similar.
      Furthermore, the results show that the metabolic capability of human for psoralen
      and isopsoralen are weaker than other mammal species. The results of this work
      are useful for studying the metabolism mechanism of psoralen/isopsolaren, and
      choosing the most relevant animal species for investigation of
      psoralen/isopsolaren from experimental animals to human.

PMID- 28448891
TI  - Plasma ferritin, C-reactive protein, and risk of incident type 2 diabetes in
      Singapore Chinese men and women.
AB  - AIMS: Ferritin is postulated to be involved in diabetogenesis as a marker of iron
      stores. We prospectively examined the association between ferritin levels and
      type 2 diabetes (T2D) risk in a Chinese population. METHODS: Plasma ferritin
      concentrations were assayed among 485 diabetes cases and 485 controls nested
      within the Singapore Chinese Health Study. Cases and controls were matched on
      age, gender, date of blood collection, and dialect group. Participants were free
      of diagnosed diabetes, cardiovascular disease, and cancer at blood collection
      (1999-2004). Incident self-reported T2D cases were identified at follow-up II
      interview (2006-2010). Multivariable conditional logistic regression models were
      used to compute the odds ratio (OR) and the corresponding 95% confidence
      intervals (CIs). RESULTS: After adjusting for T2D risk factors, including high
      sensitivity C-reactive protein (hs-CRP), adiponectin, triglycerides, HDL
      cholesterol and alanine aminotransferase, the OR comparing the highest versus
      lowest quartile of ferritin levels was 1.87 (95% CI 1.10-3.19) (P-trend=0.004).
      When the analysis was limited to participants with hs-CRP<1.5mg/L (below median;
      n=482), the OR comparing extreme quartiles of ferritin levels was 1.16 (95% CI
      0.62-2.16; P-trend=0.63); while the corresponding OR was 2.51 (95% CI 1.31-4.79;
      P-trend<0.001) when confined to those with hs-CRP>=1.5mg/L (n=488; P
      interaction=0.022). Compared to participants with both ferritin and hs-CRP levels
      below median, those with both levels above median had markedly increased T2D risk
      (P-interaction for multiplicative scale=0.037). CONCLUSIONS: The elevation of
      blood ferritin levels, in the presence of raised hs-CRP, was significantly
      associated with increased risk of T2D.

PMID- 28448892
TI  - Role of procalcitonin in infected diabetic foot ulcer.
AB  - AIMS: Procalcitonin (PCT) has been recently accepted as a marker for diagnosing
      infection. The aim of the present study was to determine whether PCT levels are
      associated with infection severity of diabetic foot ulcers and whether PCT levels
      would be helpful to differentiate infected diabetic foot ulcer (IDFU) from IDFU
      associated with other infectious diseases (IDFU+O). METHODS: We prospectively
      included 123 diabetic patients hospitalized for IDFU. Infection severity of
      diabetic foot ulcers was graded according to the Infectious Diseases Society of
      America-International Working Group on the Diabetic Foot clinical classification
      of diabetic foot infection. Chest radiograph, urinalysis, urine microscopy, urine
      culture, and blood cultures (if fever was present) were performed for all
      patients to diagnose other infectious diseases. Laboratory parameters were
      measured from blood venous samples. RESULTS: PCT (Spearman's rho=0.338, P<0.001)
      and C-reactive protein (Spearman's rho=0.477, P<0.001) levels were significantly
      associated with infection severity of diabetic foot ulcers. However, only PCT
      levels could differentiate patients with associated infectious diseases from
      patients with no concomitant infection (area under the receiver-operator
      characteristic curve 0.869, P<0.0001; cut-off value 0.59; sensitivity 94.7;
      specificity 88.5). CONCLUSION: PCT and CRP levels positively correlated with
      infection severity of diabetic foot ulcers and PCT levels>0.59ng/mL in patients
      with IDFU may be associated with other systemic bacterial infection.

PMID- 28448894
TI  - IL-33 improves the suppressive potential of regulatory T cells in patients with
      type 1 diabetes.
AB  - AIMS: The presented study was aimed to analyze the influence of IL-33 on
      regulatory T cells (Tregs) suppressive potential in patients with type 1
      diabetes. METHODS: We analyzed the ability of IL-33 treated Tregs to inhibit the
      production of IFN-gamma by effector T lymphocytes in an in vitro co-culture. The
      study group consisted of 22 patients with type 1 diabetes and 12 age and sex
      matched healthy individuals. RESULTS: Our findings revealed that in vitro IL-33
      treatment of Tregs derived from patients with type 1 diabetes resulted in
      quantitative as well as qualitative changes in this cell population, confirming
      immunoregulatory features of IL-33. CONCLUSION: IL-33 could be considered as a
      potential therapeutic tool in adoptive therapies of type 1 diabetes.

PMID- 28448895
TI  - Incidence of diabetic ketoacidosis among patients with type 2 diabetes mellitus
      treated with SGLT2 inhibitors and other antihyperglycemic agents.
AB  - AIMS: To estimate and compare incidence of diabetes ketoacidosis (DKA) among
      patients with type 2 diabetes who are newly treated with SGLT2 inhibitors
      (SGLT2i) versus non-SGLT2i antihyperglycemic agents (AHAs) in actual clinical
      practice. METHODS: A new-user cohort study design using a large insurance claims
      database in the US. DKA incidence was compared between new users of SGLT2i and
      new users of non-SGLT2i AHAs pair-matched on exposure propensity scores (EPS)
      using Cox regression models. RESULTS: Overall, crude incidence rates (95% CI) per
      1000 patient-years for DKA were 1.69 (1.22-2.30) and 1.83 (1.58-2.10) among new
      users of SGLT2i (n=34,442) and non-SGLT2i AHAs (n=126,703). These rates more than
      doubled among patients with prior insulin prescriptions but decreased by more
      than half in analyses that excluded potential autoimmune diabetes (PAD). The
      hazard ratio (95% CI) for DKA comparing new users of SGLT2i to new users of non
      SGLT2i AHAs was 1.91 (0.94-4.11) (p=0.09) among the 30,196 EPS-matched pairs
      overall, and 1.13 (0.43-3.00) (p=0.81) among the 27,515 EPS-matched pairs that
      excluded PAD. CONCLUSIONS: This was the first observational study that compared
      DKA risk between new users of SGLT2i and non-SGLT2i AHAs among patients with type
      2 diabetes, and overall no statistically significant difference was detected.

PMID- 28448893
TI  - Diabetes status modifies the association between carotid intima-media thickness
      and incident heart failure: The Atherosclerosis Risk in Communities study.
AB  - AIMS: Increasing carotid intima-media thickness (CIMT) is associated with
      incident heart failure (HF). We investigated whether this association differs by
      diabetes status. METHODS: We characterized 13,590 Atherosclerosis Risk in
      Communities Study participants free of baseline HF into normal fasting glucose
      (NFG, glucose <100mg/dl), impaired fasting glucose (IFG, glucose 100-125mg/dl),
      and type 2 diabetes (T2D, glucose >=126mg/dl, self-report, or use of diabetes
      drugs). CIMT was assessed by B-mode ultrasound. Incident HF was defined using ICD
      9 or 10 codes from hospitalizations and death certificates. Cox regression was
      used to estimate hazard ratios (HR) for incident HF, adjusting for age, sex,
      race, education, hypertension medication, blood pressure, BMI, waist
      circumference, HDL, LDL, triglycerides, lipid-lowering medication, smoking,
      alcohol, serum creatinine, and interim CHD. RESULTS: T2D participants had higher
      mean CIMT (0.79+/-0.20mm), compared to IFG (0.75+/-0.19mm) and NFG (0.70+/
      0.17mm) (p<0.0001). Over 20.6years of median follow-up, 15% developed HF. Rates
      of HF (per 1000 person-years) were substantially higher for those with T2D
      (24.7), compared to IFG (7.7) and NFG (5.8). In adjusted analyses, the CIMT-HF
      association was significantly modified by diabetes status (Pinteraction=0.015):
      for NFG (HR per SD increase in CIMT: 1.27; 95%CI: 1.20-1.34), IFG (HR 1.18;
      95%CI: 1.11-1.25) and T2D (HR 1.12; 95%CI: 1.05-1.21). CONCLUSIONS: CIMT is
      associated with increased risk of HF, particularly among persons without
      diabetes. Due to a high absolute risk of HF among adults with T2D, CIMT may be a
      less reliable predictor.

PMID- 28448897
TI  - A performance evaluation of Nextera XT and KAPA HyperPlus for rapid Illumina
      library preparation of long-range mitogenome amplicons.
AB  - Next-generation sequencing (NGS) facilitates the rapid and high-throughput
      generation of human mitochondrial genome (mitogenome) data to build population
      and reference databases for forensic comparisons. To this end, long-range
      amplification provides an effective method of target enrichment that is amenable
      to library preparation assays employing DNA fragmentation. This study compared
      the Nextera XT DNA Library Preparation Kit (Illumina, San Diego, CA) and the KAPA
      HyperPlus Library Preparation Kit (Kapa Biosystems, Wilmington, MA) for enzymatic
      fragmentation and indexing of ~8500bp mitogenome amplicons for Illumina
      sequencing. The Nextera XT libraries produced low-coverage regions that were
      consistent across all samples, while the HyperPlus libraries resulted in
      uniformly high coverage across the mitogenome, even with reduced-volume reaction
      conditions. The balanced coverage observed from KAPA HyperPlus libraries enables
      not only low-level variant calling across the mitogenome but also increased
      sample multiplexing for greater processing efficiency.

PMID- 28448896
TI  - Differentially methylated embryonal Fyn-associated substrate (EFS) gene as a
      blood-specific epigenetic marker and its potential application in forensic
      casework.
AB  - DNA methylation patterns have the ability to reveal the activities of genes
      within a certain tissue at a particular time point. Tissue-specific DNA
      methylation patterns have been previously investigated for their applicability in
      the identification of forensically relevant body fluids, however there is still a
      lack in robust markers. While following a genome-wide scale investigation has a
      great potential to reveal useful tissue-specific changes, a gene-targeted
      approach can also lead to significant outcomes, especially in genomic locations
      not included in the genome-wide experiments. In this study, the potential of the
      candidate embryonal Fyn-associated substrate (EFS) gene for the positive
      identification of whole blood was investigated. For this purpose, the methylation
      profile of a selected genomic region containing a total of 10 CpG sites was
      analysed in 124 individuals via bisulfite pyrosequencing. Volunteers donated
      various forensically relevant tissues, including whole blood, saliva, seminal
      fluid, vaginal fluid and menstrual secretion. Whole blood showed the highest
      levels of DNA methylation (mean=0.67), while semen samples were found to be very
      low methylated (mean=0.06). The remaining tissues demonstrated partial mean
      methylation levels; more specifically, saliva - 0.43, vaginal fluid - 0.22 and
      menstrual blood - 0.22. One out of the 10 analysed CpG sites, CpG4, showed to be
      more robust, resulting in not only the highest methylation difference between
      blood and the rest of the tissues, but also the lowest inter-individual
      methylation difference. The proposed pyrosequencing assay was found to be
      accurate, linear and reproducible. Lastly, the method's applicability to forensic
      casework was assessed via the analysis of very old bloodstains stored up to 18
      years, blood DNA samples stored long-term up to 9 years, mixed stains as well as
      other 'forensic-like' samples. In the majority of cases the expected methylation
      ratios were obtained indicating a stable DNA methylation pattern, however caution
      is necessary when analysing low quantity and/or quality samples due to potential
      stochastic effects. Future validation experiments can shed more light into the
      usefulness of EFS locus as a promising blood-specific epigenetic marker.

PMID- 28448898
TI  - Kinematic gait pattern in children with cerebral palsy and leg length
      discrepancy: Effects of an extra sole.
AB  - : The gait pattern in children with cerebral palsy (CP) often differs from
      normal, with slow velocity, problem with foot clearance and increased stress on
      joints. Several factors, such as muscle tone, impaired motor control, muscle
      contractures, skeletal deformities and leg length discrepancy affect gait. Leg
      length discrepancy can be treated surgically or with elevation of the shoe on the
      short leg. The purpose of this study was to examine whether compensating for leg
      length discrepancy, with elevation of the sole, leads to a change in movement
      pattern during walking in children with spastic CP. RESULTS: Ten children with
      spastic CP, able to walk without aids, and 10 typically developing (TD) children
      aged between seven and 14 years were assessed with 3D gait analysis: 1) barefoot,
      2) with shoes and 3) with an extra sole beneath the shoe for the shorter leg. All
      children with CP had a leg length discrepancy of more than or equal to 1.0cm. In
      the barefoot condition, the velocity was slower and the stride length was
      shorter, in children with CP compared with TD. The stride length and gait
      velocity increased in children with CP with shoes and shoe+sole and the stance
      time became more symmetrical. Among children with CP, there was more flexion in
      the longer leg relative to the short leg during barefoot walking. Differences in
      the kinematic pattern between the long and the short leg decreased with the extra
      sole.

PMID- 28448899
TI  - Undesirable properties of the dimensionless normalisation for spatio-temporal
      variables.
AB  - We used theory and empirical data to demonstrate three undesirable properties of
      the dimensionless normalisation technique for gait spatio-temporal parameters.
      Firstly, it may not fully remove the correlation between leg length and spatio
      temporal parameters. Secondly, it induces spurious correlation among spatio
      temporal parameters, which might obscure their true correlation structure.
      Thirdly, it induces spurious correlation with external covariates, which
      complicates further statistical modelling. Therefore, depending on the
      objectives, we propose alternatives. If the objective is to compare datasets but
      remove the confounding effect of leg length, residualisation may be an
      alternative, although the generalisability of the residualisation is less well
      established than dimensionless normalisation. If the objective is to build a
      regression model, the raw spatio-temporal parameters could be used with leg
      length, or a function of leg length, as an explicit regressor to avoid spurious
      correlation. If correlation is the objective, partial correlation can be used
      instead.

PMID- 28448900
TI  - Dual responsive magnetic composite nanogels for thermo-chemotherapy.
AB  - With the onset of hyperthermia and their advantage in increasing vascular
      perfusion and permeability in the cancer milieu, thermo-responsive polymers have
      become an attractive candidate for designing therapeutic nano-vehicles for
      targeted on-demand delivery of bioactive agents. For this purpose, we developed a
      dual (thermo- and pH-) responsive nanotherapeutic composite system rendering a
      combinational therapy of hyperthermia mediated drug delivery. This composite
      system comprises of magnetic chitosan-g-PNVCL (MCP) polymeric nanogels loaded
      with anticancer drug, Doxorubicin (DOX). The size distribution and the stability
      of the MCP nanogels have been characterized using DLS and Zeta-potential studies.
      XRD and TG-DTA confirms the presence of magnetic nanoparticles loaded onto MCP
      nanogel. ICP-AES analysis was done to determine the amount of iron content in the
      MCP nanogels. The magnetic property of the MCP nanogels was estimated to be ~37
      emu/g using Vibrating Sample Magnetometer (VSM). The heating ability of MCP
      nanogels was calculated to be ~204W/g for the concentration of 2mg/mL using time
      dependent Specific Absorption Rate (SAR) method. Magnetic field induced thermo
      responsive and pH responsive drug release studies were carried out and it was
      found that MCP nanogels have a good on-demand drug release properties. The DOX
      MCP nanogels were evaluated for its in vitro killing efficacy of breast cancer
      cells MCF 7 and MDAMB 231 cells with synergistic effects of both hyperthermia and
      chemotherapy in presence of magnetic field at the concentration of 2mg/mL. Thus,
      MCP nanogels can be a potential dual modal on-demand hyperthermia mediated drug
      delivery platform for the breast cancer treatment.

PMID- 28448902
TI  - Surface-modified TiO2 nanoparticles with ascorbic acid: Antioxidant properties
      and efficiency against DNA damage in vitro.
AB  - The antigenotoxic and antioxidative properties of surface-modified TiO2
      nanoparticles (NPs) with ascorbic acid (AA) were compared with those of
      constituents (free AA and bare TiO2 NPs). Colloids consisting of the TiO2 NPs
      with anatase crystal structure were prepared by acidic hydrolysis of TiCl4. The
      synthesized TiO2 NPs were characterized using transmission electron microscopy
      and X-ray diffraction analysis. The charge transfer (CT) complex formation
      between surface Ti atoms and AA is indicated by immediate appearance of red
      color. Composition and stability constants of CT complex were determined using
      Job's method and Banesi-Hildebrand analysis, respectively. The surface structure
      of CT complex was determined from infra-red spectra of free and bound AA to the
      surface Ti atoms. The experimental data were supported with quantum chemical
      calculations based on density functional theory (DFT). The antigenotoxic
      potential of CT complex was evaluated in leukocytes of whole blood cells in vitro
      by comet assay method. For evaluation of antioxidant properties, total
      antioxidant status (TAS) and total oxidant status (TOS) were determined in human
      serum pool in vitro. The presented results indicate that bare TiO2 NPs have more
      pronounced antigenotoxic effects in comparison with either surface-modified TiO2
      NPs with AA or free AA. No significant differences between the antigenotoxic and
      antioxidative properties of free and bound AA on the TiO2 NPs were noticed in the
      investigated concentration range. It seems that surface-modified TiO2 NPs with AA
      and/or similar compounds can be used to maintain its beneficial activities.

PMID- 28448901
TI  - Tailoring of TiO2 films by H2SO4 treatment and UV irradiation to improve
      anticoagulant ability and endothelial cell compatibility.
AB  - Surfaces with dual functions that simultaneously exhibit good anticoagulant
      ability and endothelial cell (EC) compatibility are desirable for blood contact
      materials. However, these dual functions have rarely been achieved by inorganic
      materials. In this study, titanium dioxide (TiO2) films were treated by sulphuric
      acid (H2SO4) and ultraviolet (UV) irradiation successively (TiO2H2SO4-UV),
      resulting in good anticoagulant ability and EC compatibility simultaneously. We
      found that UV irradiation improved the anticoagulant ability of TiO2 films
      significantly while enhancing EC compatibility, though not significantly. The
      enhanced anticoagulant ability could be related to the oxidation of surface
      adsorbed hydrocarbons and increased hydrophilicity. The H2SO4 treatment improved
      the anticoagulant ability of TiO2 films slightly, while UV irradiation improved
      the anticoagulant ability strongly. The enhanced EC compatibility could be
      related to the increased surface roughness and positive charges on the surface of
      the TiO2 films. Furthermore, the time-dependent degradation of the enhanced EC
      compatibility and anticoagulant ability of TiO2H2SO4-UV was observed. In summary,
      TiO2H2SO4-UV expressed both excellent anticoagulant ability and good EC
      compatibility at the same time, which could be desirable for blood contact
      materials. However, the compatibility of TiO2H2SO4-UV with smooth muscle cells
      (SMCs) and macrophages was also improved. More effort is still needed to
      selectively improve EC compatibility on TiO2 films for better re
      endothelialization.

PMID- 28448903
TI  - Violence, trauma and living with HIV: Longitudinal predictors of initiating
      crystal methamphetamine injection among sex workers.
AB  - BACKGROUND: Despite rapid increases in crystal methamphetamine (CM) use worldwide
      and established gendered patterns of use, empirical research on CM injection
      initiation among sex workers is limited. Given the wide range of harms associated
      with CM, alongside stimulant effects including sexual dis-inhibition and
      prolonged awake-ness, this study aimed to longitudinally investigate socio
      structural predictors of initiating CM injection among sex workers in Vancouver,
      Canada. METHODS: Data (2010-2014) were drawn from a community-based cohort of
      women sex workers: AESHA (An Evaluation of Sex Workers Health Access).
      Participants completed bi-annual interviewer-administered questionnaires and
      HIV/STI testing. Kaplan Meier methods and Cox proportional hazards regression
      were used to model predictors of CM injection initiation among CM injection-naive
      participants. RESULTS: Of 455 participants eligible at baseline, 14.3% (n=65)
      injected CM for the first time over follow-up, with an incidence density of 6.79
      per 100 person-years (95% Confidence Interval [CI] 5.30-8.69). In multivariable
      analysis, injection heroin use (Adjusted Hazard Ratio [AHR] 6.11; 95%CI 3.24
      11.52), having an intimate partner who injects drugs (AHR 2.93; 95%CI 1.57-5.46),
      workplace violence (AHR 2.85; 95%CI 1.74-4.67), HIV seropositivity (AHR 2.69;
      95%CI 1.45-5.00), and childhood abuse (AHR 1.86; 95%CI 0.99-3.49) were
      independently associated with initiating CM injection. CONCLUSIONS: Findings
      underscore the gendered and social risk environment of CM injection initiation
      among sex workers. The strong influences of historical/workplace violence,
      coupled with heroin injection (known to be self-medicating for post-traumatic
      stress) as a primary risk pathway, emphasize the urgency of increasing access to
      integrated, trauma-informed addiction treatment and HIV care for marginalized
      women.

PMID- 28448904
TI  - Support for marijuana legalization in the US state of Washington has continued to
      increase through 2016.
AB  - BACKGROUND: Support for the legalization of recreational marijuana continues to
      increase across the United States and globally. In 2016, recreational marijuana
      was legalized in the most populous US state of California, as well as three other
      states. The primary aim of this study was to examine trends in support for
      recreational marijuana legalization in Washington, a state which has had legal
      recreational marijuana for almost four years, using data collected over the four
      years post-legalization. A secondary aim was to examine trends in support for the
      cultivation of marijuana for personal use. METHODS: Data come from geographically
      representative general population samples of adult (aged 18 and over) Washington
      residents collected over five timepoints (every six months) between January 2014
      and April 2016 (N=4101). Random Digit Dial was used for recruitment. Statistical
      analyses involved bivariate comparisons of proportions across timepoints and
      subgroups (defined by age, gender, and marijuana user status), and multivariable
      logistic regression controlling for timepoint (time) to formally test for trend
      while controlling for demographic and substance use covariates. All analyses
      adjusted for probability of selection. RESULTS: Support for legalization in
      Washington has significantly increased: support was 64.0% (95% CI: 61.2%-67.8%)
      at timepoint 1 and 77.9% (95% CI: 73.2%-81.9%) at timepoint 5. With each six
      months' passing, support increased 19% on average. We found no statistically
      significant change in support for home-growing. CONCLUSIONS: Support for
      marijuana legalization has continued to significantly increase in a state that
      has experienced the policy change for almost four years.

PMID- 28448906
TI  - Variation in the toxicity of sediment-associated substituted phenylamine
      antioxidants to an epibenthic (Hyalella azteca) and endobenthic (Tubifex tubifex)
      invertebrate.
AB  - Substituted phenylamine antioxidants (SPAs) are produced in relatively high
      volumes and used in a range of applications (e.g., rubber, polyurethane);
      however, little is known about their toxicity to aquatic biota. Therefore,
      current study examined the effects of chronic exposure (28 d) to four sediment
      associated SPAs on epibenthic (Hyalella azteca) and endobenthic (Tubifex tubifex)
      organisms. In addition, acute (96-h), water-only exposures were conducted with H.
      azteca. Mortality, growth and biomass production were assessed in juvenile H.
      azteca exposed to diphenylamine (DPA), N-phenyl-1-napthylamine (PNA), N-(1,3
      dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (DPPDA), or 4,4'-methylene-bis[N
      sec-butylaniline] (MBA). Mortality of adult T. tubifex and reproduction were
      assessed following exposure to the four SPAs. The 96-h LC50s for juvenile H.
      azteca were 1443, 109, 250, and >22 MUg/L and 28-d LC50s were 22, 99, 135, and
      >403 MUg/g dry weight (dw) for DPA, PNA, DPPDA, and MBA, respectively.
      Reproductive endpoints for T. tubifex (EC50s for production of juveniles > 500
      MUm: 15, 9, 4, 3.6 MUg/g dw, for DPA, PNA, DPPDA, and MBA, respectively) were an
      order of magnitude more sensitive than endpoints for juvenile H. azteca and
      mortality of adult worms. The variation in toxicity across the four SPAs was
      likely related to the bioavailability of the sediment-associated chemicals, which
      was determined by the chemical properties of the SPAs (e.g., solubility in water,
      Koc). The variation in the sensitivity between the two species was likely due to
      differences in the magnitude of exposure, which is a function of the life
      histories of the epibenthic amphipod and the endobenthic worm. The data generated
      from this study will support effect characterization for ecological risk
      assessment.

PMID- 28448907
TI  - Characterization of typical metal particles during haze episodes in Shanghai,
      China.
AB  - Aerosol particles were collected during three heavy haze episodes at Shanghai in
      the winter of 2013. Transmission electron microscopy (TEM) coupled with energy
      dispersive X-ray spectroscopy was used to study the morphology and speciation of
      typical metal particles at a single-particle level. In addition, time-of-flight
      aerosol mass spectrometry (ATOFMS) was applied to identify the speciation of the
      Fe-containing particles. TEM analysis indicated that various metal-containing
      particles were hosted by sulfates, nitrates, and oxides. Fe-bearing particles
      mainly originated from vehicle emissions and/or steel production. Pb-, Zn-, and
      Sb-bearing particles were mainly contributed by anthropogenic sources. Fe-bearing
      particles were clustered into six groups by ATOFMS: Fe-Carbon, Fe-Inorganic, Fe
      Trace metal, Fe-CN, Fe-PO3, and Fe-NO3. ATOFMS data suggested that Fe-containing
      particles corresponded to different origins, including industrial activities,
      resuspension of dusts, and vehicle emissions. Fe-Carbon and Fe-CN particles
      displayed significant diurnal variation, and high levels were observed during the
      morning rush hours. Fe-Inorganic and Fe-Trace metal particle levels peaked at
      night. Furthermore, Fe-Carbon and Fe-PO3 were mainly concentrated in the fine
      particles. Fe-CN, Fe-Inorganic, and Fe-Trace metal exhibited bimodal
      distribution. The mixing state of the particles revealed that all Fe-bearing
      particles tended to be mixed with sulfate and nitrate. The data presented herein
      is essential for elucidating the origin, evolution processes, and health effects
      of metal-bearing particles.

PMID- 28448905
TI  - Drug use generations and patterns of injection drug use: Birth cohort differences
      among people who inject drugs in Los Angeles and San Francisco, California.
AB  - OBJECTIVES: A robust literature documents generational trends in drug use. We
      examined the implications of changing national drug use patterns on drug
      injection histories of diverse people who inject drugs (PWID). METHODS: Drug use
      histories were collected from 776 active PWID in 2011-13. Using descriptive
      statistics, we examine drug use initiation by year and birth cohort (BC)
      differences in drug first injected. A multivariate linear regression model of
      time to injection initiation ([TTII] (year of first injection minus year of first
      illicit drug use) was developed to explore BC differences. RESULTS: The first
      drug injected by BC changed in tandem with national drug use trends with heroin
      declining from 77% for the pre-1960's BC to 58% for the 1960's BC before
      increasing to 71% for the 1990's BC. Multivariate linear regression modeling
      found that shorter TTII was associated with the 1980's/1990's BC (-3.50 years;
      95% Confidence Interval [CI]=-0.79, -6.21) as compared to the 1970's BC. Longer
      TTII was associated with being female (1.65 years; 95% CI=0.40, 2.90), African
      American (1.69 years; 95% CI=0.43, 2.95), any substance use treatment prior to
      injection (4.22 years; 95% CI=2.65, 5.79), and prior non-injection use of drug
      that was first injected (3.29 years; 95% CI=2.19, 4.40). CONCLUSION: National
      drug trends appear to influence injection drug use patterns. The prescription
      opiate drug era is associated with shorter TTII. Culturally competent,
      demographically and generationally-targeted prevention strategies to combat
      transitions to drug injection are needed to prevent or shorten upstream increases
      in risky drug use practices on a national level.

PMID- 28448908
TI  - Biological impacts of glyphosate on morphology, embryo biomechanics and larval
      behavior in zebrafish (Danio rerio).
AB  - All of these days, residues of herbicides such as glyphosate are widely
      distributed in the environment. The ubiquitous use of glyphosate has drawn
      extensive attention to its toxicity as an organic pollutant. In this study, we
      employed larval zebrafish as an animal model to evaluate the effect of different
      concentrations of glyphosate on early development via morphological,
      biomechanics, behavioral and physiological analyses. Morphological results showed
      that an obvious delay occurred in the epiboly process and body length, eye and
      head area were reduced at concentrations higher than 10 mg/L. The expression of
      ntl (no tail) shortened and krox20 (also known as Egr2b, early growth response
      2b) changed as the glyphosate concentration increased, but there was no change in
      the expression of shh (sonic hedgehog). In addition, biomechanical analysis of
      the elasticity of chorion indicated that treated embryos' surface tension was
      declined. Furthermore, a 48-h locomotion test revealed that embryonic exposure to
      glyphosate significantly elevated locomotor activities, which is probably
      attributed to motoneuronal damage. The decreased surface tension of chorion and
      the increased locomotive activities may contribute to the hatching rates after
      glyphosate treatment. Our study enriches the researches of evaluating glyphosate
      toxicity and probablely plays a warning role in herbicides used in farming.

PMID- 28448909
TI  - Changes in heavy metal mobility and availability from contaminated wetland soil
      remediated with combined biochar-compost.
AB  - The combination of biochar and compost has been proven to be effective in heavy
      metals contaminated wetland soil restoration. However, the influence of different
      proportions between biochar and compost on immobilization of heavy metals in soil
      has been less studied up to date. Therefore, we investigated the effect of
      different ratios of biochar-compost mixtures on availability and speciation
      distribution of heavy metals (Cd, Zn and Cu) in wetland soil. The results showed
      that applying all amendment combinations into wetland soil increased gradually
      the total organic carbon (TOC) and water-extract organic carbon (WEOC) as the
      compost percentage rose in biochar-composts. The higher pH was obtained in a
      certain biochar addition (20% and 40%) in combinations due to efficient
      interaction of biochar with compost. All amendments could significantly decrease
      availability of Cd and Zn mainly from pH change, but increase available Cu
      concentration as the result of increased water-extract organic carbon and high
      total Cu content in compost. Moreover, amendments can decrease easily
      exchangeable fraction and increase reducible of Cd and Zn greatly with increase
      of compost content in combinations, while amendments containing compost promote
      transformation of Cu from Fe/Mn oxide and residual fractions to organic bindings.
      These results demonstrate that different ratios of biochar and compost have a
      significant effect on availability and speciation of heavy metals in multi-metal
      contaminated wetland soil.

PMID- 28448910
TI  - Exposure to 2,2',4,4'-tetrabromodiphenyl ether at late gestation modulates
      placental signaling molecules in the mouse model.
AB  - Polybrominated diphenyl ethers (PBDEs) are flame retardants generally employed in
      manufacturing household items. Surface water may remove and carry these chemicals
      to the drainage upon disposal of the items, and ultimately the chemicals enter
      our food chain. 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a PBDE congener
      commonly found in contaminated seafood. The placenta is the site of nutrient
      exchange and is responsible for reproductive hormone secretion during pregnancy.
      In the present study, pregnant ICR mice were given p.o. daily doses of BDE-47 at
      0, 0.36, 3.6, 36 mg/kg for 4 days (from E13.5 to E16.5). Compared to the control
      group, increased rates of stillborn and low birth weight were observed in mice
      treated with 36 mg BDE-47/kg. Plasma testosterone and progesterone levels were
      reduced in mice treated with 36 mg BDE-47/kg. In addition, the group treated with
      3.6 mg/kg of BDE-47 displayed decreased growth hormone (Gh) peptide expression in
      the placental tissue extracted at E17.5. As this peptide stimulates growth, the
      expression pattern might suggest compromised fetal development. Further analysis
      indicated that mitogen-activated protein kinases (MAPK) were activated in the
      placental tissue of the BDE-47-treatment groups. The activation of these
      signaling molecules might affect the hormonal and other physiological functions
      in the tissue.

PMID- 28448911
TI  - Adsorption of polar organic molecules on sediments: Case-study on Callovian
      Oxfordian claystone.
AB  - The release and transport of anthropogenic organic matter through the geosphere
      is often an environmental criterion of safety. Sedimentary rocks are widely
      studied in this context as geological barriers for waste management. It is the
      case of Callovian-Oxfordian claystone (COx), for which several studies report
      adsorption of anthropogenic organic molecules. In this study, we evaluated and
      reviewed adsorption data of polar organic molecules on COx claystone. Experiments
      were performed on raw claystone, decarbonated and clay fractions. Adsorption
      isotherms were measured with adsorbates of various polarities: adipate, benzoate,
      ortho-phthalate, succinate, gluconate, oxalate, EDTA, citrate. A significant
      adsorption was observed for multidentate polycarboxylic acids as evidenced with
      phthalate, succinate, oxalate, gluconate, EDTA and citrate (Rd = 1.53, 3.52, 8.4,
      8.8, 12.4, 54.7 L kg-1 respectively). Multiple linear regression were performed
      as a statistical analysis to determine the predictors from these adsorption data.
      A linear correlation between adsorption data (Rd) and dipole moment (MU) of
      adsorbates was evidenced (R2 = 0.91). Molecules with a high dipole moment, MU(D)
      > 2.5, displayed a significant adsorption, Rd?1 L kg-1. A qualitative correlation
      can be easily estimated using the water/octanol partition coefficient, Pow, of
      adsorbates (R2 = 0.77). In this case, two opposite trends were distinguished for
      polar and apolar molecules. The use of organic carbon content in sediments is
      relevant for predicting adsorption of apolar compounds, log (Pow)>+1. The
      oxides/clays contents may be relevant regarding polar molecules, log
      (apparentPow)<-1. The proposed scheme offers a general methodology for
      investigation of geo-barriers towards heterogeneous organic plumes.

PMID- 28448912
TI  - Effects of low levels of ultraviolet radiation on antioxidant mechanisms of
      Japanese Medaka (Oryzias latipes).
AB  - Extreme weather events like drought are expected to increase with climate change,
      which will increase exposure of freshwater fish to ultraviolet (UV) radiation.
      Compared to fully grown adult fish, fish in early life stages are more
      susceptible to UV radiation due to the lack of well-developed pigmentation. Even
      though several studies have described affectation of fish health after exposure
      to UV radiation, most of the studies have used intensities that are only found on
      the surface of the earth crust or at shallow depths in water bodies, and little
      is known about impacts of weaker UV radiation, which can be found in deep water.
      This study showed effects on the antioxidant system of Japanese Medaka after 7
      days of exposure to very low intensities of UV radiation, levels that can be
      found at deep locations in lakes and rivers. Exposure to UV radiation (UVA: 360.1
      +/- 18.4 MUW cm-2 for a dose of 21.6 +/- 1.2 mJ cm-2 min-1, and UVB: 6.3 +/- 0.5
      MUW cm-2 for a dose of 0.38 +/- 0.03 mJ cm-2 min-1) caused a reduction in the
      catalase activity (over 50%) and enhanced oxidative damage to lipids. Results of
      this study showed that environmentally relevant, low levels of UV radiation
      affect mechanisms by which fish deal with enhanced production of reactive oxygen
      species and oxidative damage. The results raise concerns about early life stages
      of fish under scenarios of increased exposure to solar light, such as in tropic
      regions or during summer in temperate regions.

PMID- 28448913
TI  - Temporal characterization of flowback and produced water quality from a
      hydraulically fractured oil and gas well.
AB  - This study examined water quality, naturally-occurring radioactive materials
      (NORM), major ions, trace metals, and well flow data for water used and produced
      from start-up to operation of an oil and gas producing hydraulically-fractured
      well (horizontal) in the Denver-Julesburg (DJ) Basin in northeastern Colorado.
      Analysis was conducted on the groundwater used to make the fracturing fluid, the
      fracturing fluid itself, and nine flowback/produced water samples over 220days of
      operation. The chemical oxygen demand of the wastewater produced during operation
      decreased from 8200 to 2500mg/L, while the total dissolved solids (TDS) increased
      in this same period from 14,200 to roughly 19,000mg/L. NORM, trace metals, and
      major ion levels were generally correlated with TDS, and were lower than other
      shale basins (e.g. Marcellus and Bakken). Although at lower levels, the salinity
      and its origin appear to be the result of a similar mechanism to that of other
      shale basins when comparing Cl/Br, Na/Br, and Mg/Br ratios. Volumes of returned
      wastewater were low, with only 3% of the volume injected (11millionliters)
      returning as flowback by day 15 and 30% returning by day 220. Low levels of TDS
      indicate a potentially treatment-amenable wastewater, but low volumes of flowback
      could limit onsite reuse in the DJ Basin. These results offer insight into the
      temporal water quality changes in the days and months following flowback, along
      with considerations and implications for water reuse in future hydraulic
      fracturing or for environmental discharge.

PMID- 28448914
TI  - Reconciling agriculture and stream restoration in Europe: A review relating to
      the EU Water Framework Directive.
AB  - Agriculture is widespread across the EU and has caused considerable impacts on
      freshwater ecosystems. To revert the degradation caused to streams and rivers,
      research and restoration efforts have been developed to recover ecosystem
      functions and services, with the European Water Framework Directive (WFD) playing
      a significant role in strengthening the progress. Analysing recent peer-reviewed
      European literature (2009-2016), this review explores 1) the conflicts and
      difficulties faced when restoring agriculturally impacted streams, 2) the aspects
      relevant to effectively reconcile agricultural land uses and healthy riverine
      ecosystems and 3) the effects and potential shortcomings of the first WFD
      management cycle. Our analysis reveals significant progress in restoration
      efforts, but it also demonstrates an urgent need for a higher number and detail
      of restoration projects reported in the peer-reviewed literature. The first WFD
      cycle ended in 2015 without reaching the goal of good ecological status in many
      European water-bodies. Addressing limitations reported in recent papers,
      including difficulties in stakeholder integration and importance of small
      headwater streams, is crucial. Analysing recent developments on stakeholder
      engagement through structured participatory processes will likely reduce
      perception discrepancies and increase stakeholder interest during the next WFD
      planning cycle. Despite an overall dominance of nutrient-related research,
      studies are spreading across many important topics (e.g. stakeholder management,
      land use conflicts, climate change effects), which may play an important role in
      guiding future policy. Our recommendations are important for the second WFD cycle
      because they 1) help secure the development and dissemination of science-based
      restoration strategies and 2) provide guidance for future research needs.

PMID- 28448915
TI  - Ozone exposure affects tree defoliation in a continental climate.
AB  - Ground-level ozone (O3) affects trees through visible leaf injury, accelerating
      leaf senescence, declining foliar chlorophyll content, photosynthetic activity,
      growth, carbon sequestration, predisposing to pests attack and a variety of other
      physiological effects. Tree crown defoliation is one of the most important
      parameters that is representative of forest health and vitality. Effects of air
      pollution on forests have been investigated through manipulative experiments that
      are not representative of the real environmental conditions observed in the
      field. In this work we investigated the role of O3 concentration and other
      metrics (AOT40 and POD0) in affecting crown defoliation in temperate Romanian
      forests. The impacts of O3 were estimated in combination with nitrogen
      pollutants, climatic factors and orographic conditions, by applying a non-linear
      modelling approach (Random Forest and Generalised Regression Models). Ozone
      concentration and AOT40 under Romanian conditions were more important than
      meteorological parameters in affecting crown defoliation. In these particular
      conditions, POD0 never exceeded the critical level suggested by previous
      literature for forest protection, and thus was not important in affecting crown
      defoliation.

PMID- 28448916
TI  - On the necessity of improving the environmental impacts of furniture and
      appliances in net-zero energy buildings.
AB  - There is now clear evidence regarding the extensive use of furniture and
      appliances in daily human life, but there is less evidence of their impact on the
      environment. Responding to this gap in knowledge, this study focuses on an
      assessment of the environmental impacts of furniture and appliances as used in
      highly energy efficient buildings. Their primary energy, non-renewable energy and
      global warming potential indicators have been assessed by extending the
      boundaries of the Life Cycle Assessment (LCA) study beyond the building itself.
      In conclusion, we found that furniture and appliances were responsible for around
      30% of greenhouse gas emissions and non-renewable energy consumption and 15% of
      primary energy consumption comparing to the overall impacts of the building.
      Since embodied impacts represent the largest values, the process for labelling
      the appliances' energy efficiency should encompass a life-cycle point of view,
      not just a usage point of view as the case currently. Among office appliances,
      computer equipment was ranked as the highest impacting element, especially
      laptops and monitors. As for domestic appliances, refrigerators and electric
      ovens had the biggest impacts. Concerning furniture, the greatest impacts were
      from office and kitchen cabinets.

PMID- 28448917
TI  - Assessing future changes in the occurrence of rainfall-induced landslides at a
      regional scale.
AB  - According to the fifth report of the Intergovernmental Panel on Climate Change,
      an increase in the frequency and the intensity of extreme rainfall is expected in
      the Mediterranean area. Among different impacts, this increase might result in a
      variation in the frequency and the spatial distribution of rainfall-induced
      landslides, and in an increase in the size of the population exposed to landslide
      risk. We propose a method for the regional-scale evaluation of future variations
      in the occurrence of rainfall-induced landslides, in response to changes in
      rainfall regimes. We exploit information on the occurrence of 603 rainfall
      induced landslides in Calabria, southern Italy, in the period 1981-2010, and
      daily rainfall data recorded in the same period in the region. Furthermore, we
      use high-resolution climate projections based on RCP4.5 and RCP8.5 scenarios. In
      particular, we consider the mean variations between a 30-year future period (2036
      2065) and the reference period 1981-2010 in three variables assumed as proxy for
      landslide activity: annual rainfall, seasonal cumulated rainfall, and annual
      maxima of daily rainfall. Based on reliable correlations between landslide
      occurrence and weather variables estimated in the reference period, we assess
      future variations in rainfall-induced landslide occurrence for all the
      municipalities of Calabria. A +45.7% and +21.2% average regional variation in
      rainfall-induced landslide occurrence is expected in the region for the period
      2036-2065, under the RCP4.5 and RCP8.5 scenario, respectively. We also
      investigate the future variations in the impact of rainfall-induced landslides on
      the population of Calabria. We find a +80.2% and +54.5% increase in the impact on
      the population for the period 2036-2065, under the RCP4.5 and RCP8.5 scenario,
      respectively. The proposed method is quantitative and reproducible, thus it can
      be applied in similar regions, where adequate landslide and rainfall information
      is available.

PMID- 28448918
TI  - Erosion of the Alberta badlands produces highly variable and elevated heavy metal
      concentrations in the Red Deer River, Alberta.
AB  - Erosion is important in the transport of heavy metals from terrestrial to fluvial
      environments. In this study, we investigated riverine heavy metal (Cd, Cu, Hg and
      Pb) dynamics in the Red Deer River (RDR) watershed at sites upstream (n=2) and
      downstream (n=7) of the Alberta badlands, an area of naturally high erosion. At
      sites draining the badlands, total water column Cd, Cu, Hg and Pb concentrations
      frequently exceeded guidelines for the protection of freshwater biota.
      Furthermore, peak concentrations of total Cd (9.8MUgL-1), Cu (212MUgL-1), Hg
      (649ngL-1) and Pb (361MUgL-1) were higher than, or comparable to, values reported
      for rivers and streams heavily impacted by anthropogenic activities. Total
      suspended solids (TSS) explained a large proportion (r2=0.34-0.83) of the
      variation in total metal concentrations in the RDR and tributaries and metal
      fluxes were dominated by the particulate fraction (60-98%). Suspended sediment
      concentrations (Csed) and metal to aluminum ratios were generally not indicative
      of substantial sediment enrichment. Rather, the highly variable and elevated
      metal concentrations in the RDR watershed were a function of the high and
      variable suspended sediment fluxes which characterize the river system. While the
      impact of this on aquatic biota requires further investigation, we suggest
      erosion in the Alberta badlands may be contributing to Hg-based fish consumption
      advisories in the RDR. Importantly, this highlights a broader need for
      information on contaminant dynamics in watersheds subject to elevated rates of
      erosion.

PMID- 28448919
TI  - Mechanochemical mechanism of integrin clustering modulated by nanoscale ligand
      spacing and rigidity of extracellular substrates.
AB  - Experimental findings indicate that cell function and behavior such as cell
      growth, division, migration and differentiation, are subtly regulated via
      integrin-dependent cell adhesion. Cell adhesion is influenced by nanoscale ligand
      spacing and rigidity of extracellular substrates, as cell adhesion drops greatly
      when the ligand spacing is larger than ~60nm, and cell adhesion is stronger on
      stiff than soft substrates. However, how nanoscale ligand spacing and substrate
      stiffness jointly affect integrin clustering and hence nascent cell adhesion
      remains to be elucidated. To quantitatively investigate the phenomena and the
      underlying mechanochemical mechanism of integrin clustering modulated by ligand
      spacing and substrate stiffness, we introduced Monte Carlo simulations varying
      the values of ligand spacing and substrate stiffness. Moreover, the effects of
      integrin number, integrin binding free energy, integrin association free energy,
      and local ligand spacing were investigated. The simulation results showed that
      integrin clustering decreased sharply, when ligand spacing was relatively large
      such as dL>60nm in the current simulations, regardless of substrate rigidities,
      though with close spacing, the clustering increased with the substrate stiffness.
      The investigation contributes to the goals of understanding and predicting
      experimental phenomena, directing and optimizing biomaterial design, and
      manipulating integrin-dependent cell-substrate adhesion in tissue engineering.

PMID- 28448920
TI  - The effect of equiaxial stretching on the osteogenic differentiation and
      mechanical properties of human adipose stem cells.
AB  - Although mechanical cues are known to affect stem cell fate and mechanobiology,
      the significance of such stimuli on the osteogenic differentiation of human
      adipose stem cells (hASCs) remains unclear. In this study, we investigated the
      effect of long-term mechanical stimulation on the attachment, osteogenic
      differentiation and mechanical properties of hASCs. Tailor-made, pneumatic cell
      stretching devices were used to expose hASCs to cyclic equiaxial stretching in
      osteogenic medium. Cell attachment and focal adhesions were visualised using
      immunocytochemical vinculin staining on days 3 and 6, and the proliferation and
      alkaline phosphatase activity, as a sign of early osteogenic differentiation,
      were analysed on days 0, 6 and 10. Furthermore, the mechanical properties of
      hASCs, in terms of apparent Young's modulus and normalised contractility, were
      obtained using a combination of atomic force microscopy based indentation and
      computational approaches. Our results indicated that cyclic equiaxial stretching
      delayed proliferation and promoted osteogenic differentiation of hASCs.
      Stretching also reduced cell size and intensified focal adhesions and actin
      cytoskeleton. Moreover, cell stiffening was observed during osteogenic
      differentiation and especially under mechanical stimulation. These results
      suggest that cyclic equiaxial stretching modifies cell morphology, focal adhesion
      formation and mechanical properties of hASCs. This could be exploited to enhance
      osteogenic differentiation.

PMID- 28448921
TI  - Novel bone surrogates for cranial surgery training.
AB  - Parietal graft lifts are trained on human or animal specimens or are directly
      performed on patients without extensive training. In order to prevent harm to the
      patient resulting from fast rotating machinery tools, the surgeon needs to apply
      appropriate forces. Realistic haptics are essential to identify the varying
      parietal bone layers and to avoid a penetration of the brain. This however,
      requires experience and training. Therefore, in this study, bone surrogate
      materials were evaluated with the aim to provide an anatomically correct
      artificial skull cap with realistic haptic feedback for graft lift training
      procedures. Polyurethane composites made of calcium carbonate and calcium
      phosphate were developed and were used to create customized bone surrogates,
      imitating both cancellous and cortical bone. Mechanical properties of these
      surrogates were validated for drilling, milling and sawing by comparison with
      human parietal bones. For that, surgical tool tips were automatically inserted
      into artificial and human bones in a customized test bench and the maximum axial
      insertion forces were analyzed. Axial tool insertion measurements in human
      parietal bones resulted in mean maximum forces of 1.8+/-0.5N for drilling, 1.7+/
      0.3N for milling and 0.9+/-0.1N for sawing. Calcium carbonate-based materials
      achieved higher forces than the human bone for drilling and milling, and lower
      forces for sawing. The calcium phosphate-based bone surrogates showed comparable
      axial insertions forces for all investigated tools and were identified as a
      suitable surrogate for drilling (p=0.87 and 0.41), milling (p=0.92 and 0.63) and
      sawing (p=0.11 and 0.76) of the cortical layer and the cancellous bone,
      respectively. In conclusion, our findings suggest, that a suitable material
      composition for artificial parietal bones has been identified, mimicking the
      properties of human bone during surgical machinery procedures. Thus, these
      materials are suitable for surgical training and education in simulator training.

PMID- 28448922
TI  - Affine and non-affine deformations quantified in cytoskeletal networks through
      three-dimensional form-finding model.
AB  - Actin filaments and cross-linkers are main components of cytoskeletal networks in
      eukaryotic cells, and they support bending moments and axial forces respectively.
      A three-dimensional form-finding model is proposed in this work to investigate
      affine and non-affine deformations in cytoskeletal networks. In recent studies,
      modeling of cytoskeletal networks turns out to be a key piece in the cell
      mechanics puzzle. We used form-finding analysis to compute and analyze
      cytoskeletal models. A three-dimensional model is much more flexible and contains
      more elements than a two-dimensional model, and non-linear finite element
      analysis is difficult to converge. Thus, vector form intrinsic finite element
      analysis is employed here for valid results. The three-dimensional model reveals
      new behaviors beyond earlier two-dimensional models and better aligns with
      available data. Relative density of actin filaments and height of the form
      finding model both play important roles in determining cytoskeletal stiffness,
      positively and negatively, respectively. Real cytoskeletal networks are quite
      mixed in terms of affine and non-affine deformations, which are quantified by
      internal strain energy in actin filaments and cross-linkers. Results are also
      influenced by actin filament relative density and height of the model. The three
      dimensional form-finding model does provide much more room for intensive studies
      on cytoskeletal networks. In our future study, microtubules, fluidics,
      viscoelastic-plastic cross-linkers and even the whole cell model may be taken
      into account gradually to improve the cytoskeletal form-finding model.

PMID- 28448923
TI  - Impacts of Himalayas on black carbon over the Tibetan Plateau during summer
      monsoon.
AB  - The Tibetan Plateau (TP) plays important roles in global climate and environment.
      This study combines in-situ BC measurements in the Himalayas and the Indo
      Gangetic Plain (IGP) with a regional dynamical and chemical model (WRF-Chem
      model) to investigate the effect of the trans-Himalayas on black carbon (BC) from
      the IGP to the TP during Indian summer monsoon. To determine topographic effects
      of the trans-Himalayas on BC concentrations over the TP, sensitive experiments
      were conducted by applying the WRF-Chem model. The results showed that the
      reduction of the altitude of the Himalayas had an important effect on the trans
      Himalayas transport of BC. There was an obvious increase in BC concentration over
      the trans-Himalayas region, but no significant increase over the TP because the
      TP (a.m.s.l ~4km) always acted as a wall to prevent BC transport from the IGP to
      the TP. The trans-Himalayas transport of BC was strongly dependent upon
      meteorological conditions over the IGP. During summer monsoon, there were three
      types of cyclones at different locations and one kind of convergent circulation
      in the IGP. Under the condition of convergent airflows, a strong northeastward
      wind produced the trans-Himalayas transport of BC. As a result, BC concentrations
      in the southeastern TP significantly increased to 0.6-0.8MUgm-3. When the cyclone
      located in the eastern IGP, high BC concentrations over the IGP were transported
      along the foothill of the Himalayas, resulting in a significant reduction of the
      trans-Himalayas transport. When the cyclone moved to the west, the dynamical
      perturbations for the trans-Himalayas transport were weaker than the eastern
      cyclone, and the trans-Himalayas transport were enhanced in the middle and
      eastern Himalayas. This study will be helpful to assess the impacts of BC
      particles emitted from South Asia on regional climate change and ecological
      environment over the TP in the future.

PMID- 28448924
TI  - Sediment transfer at different spatial and temporal scales in the Sichuan Hilly
      Basin, China: Synthesizing data from multiple approaches and preliminary
      interpretation in the context of climatic and anthropogenic drivers.
AB  - Quantifying sediment production and transfer at different spatial and temporal
      scales in a changing environment is critical in understanding the potential
      effects of climatic and anthropogenic drivers. Accordingly, estimates of soil
      erosion and sediment production at hillslope field, first-order small catchment
      (<0.25km2) and river basin scales in the Sichuan Hilly Basin of Southwestern
      China, generated using a variety of techniques, including fallout radionuclide
      tracing, runoff plot observations, core chronology dating and conventional
      sediment flux monitoring, were synthesized and interpreted in the context of
      potential climatic and human controls. Mean annual soil erosion rates ranged from
      800Mg.km-2.yr-1 to 4500Mg.km-2.yr-1 on the basis of fallout radionuclide tracing
      and from 600Mg.km-2.yr-1 to 3300Mg.km-2.yr-1 using runoff plot monitoring on
      selected cultivated hillslopes. A high slope-channel sediment delivery ratio was
      observed, meaning that a substantial proportion of eroded sediment was delivered
      into downstream drainage channels. An obvious temporal trend of decreasing
      sediment transfer to the river channels in the first-order catchments was
      identified, which may be driven by change in regional precipitation regime and
      the implementation of multiple soil conservation and reforestation practices over
      recent decades.

PMID- 28448925
TI  - Geostatistics as a tool to improve the natural background level definition: An
      application in groundwater.
AB  - The Natural Background Level (NBL), suggested by UE BRIDGE project, is suited for
      spatially distributed datasets providing a regional value that could be higher
      than the Threshold Value (TV) set by every country. In hydro-geochemically dis
      homogeneous areas, the use of a unique regional NBL, higher than TV, could arise
      problems to distinguish between natural occurrences and anthropogenic contaminant
      sources. Hence, the goal of this study is to improve the NBL definition employing
      a geostatistical approach, which reconstructs the contaminant spatial structure
      accounting geochemical and hydrogeological relationships. This integrated mapping
      is fundamental to evaluate the contaminant's distribution impact on the NBL,
      giving indications to improve it. We decided to test this method on the Drainage
      Basin of Venice Lagoon (DBVL, NE Italy), where the existing NBL is seven times
      higher than the TV. This area is notoriously affected by naturally occurring
      arsenic contamination. An available geochemical dataset collected by 50
      piezometers was used to reconstruct the spatial distribution of arsenic in the
      densely populated area of the DBVL. A cokriging approach was applied exploiting
      the geochemical relationships among As, Fe and NH4+. The obtained spatial
      predictions of arsenic concentrations were divided into three different zones: i)
      areas with an As concentration lower than the TV, ii) areas with an As
      concentration between the TV and the median of the values higher than the TV, and
      iii) areas with an As concentration higher than the median. Following the BRIDGE
      suggestions, where enough samples were available, the 90th percentile for each
      zone was calculated to obtain a local NBL (LNBL). Differently from the original
      NBL, this local value gives more detailed water quality information accounting
      the hydrogeological and geochemical setting, and contaminant spatial variation.
      Hence, the LNBL could give more indications about the distinction between natural
      occurrence and anthropogenic contamination.

PMID- 28448926
TI  - Mass spectra features of biomass burning boiler and coal burning boiler emitted
      particles by single particle aerosol mass spectrometer.
AB  - In this study, single particle mass spectra signatures of both coal burning
      boiler and biomass burning boiler emitted particles were studied. Particle
      samples were suspended in clean Resuspension Chamber, and analyzed by ELPI and
      SPAMS simultaneously. The size distribution of BBB (biomass burning boiler
      sample) and CBB (coal burning boiler sample) are different, as BBB peaks at
      smaller size, and CBB peaks at larger size. Mass spectra signatures of two
      samples were studied by analyzing the average mass spectrum of each particle
      cluster extracted by ART-2a in different size ranges. In conclusion, BBB sample
      mostly consists of OC and EC containing particles, and a small fraction of K-rich
      particles in the size range of 0.2-0.5MUm. In 0.5-1.0MUm, BBB sample consists of
      EC, OC, K-rich and Al_Silicate containing particles; CBB sample consists of EC,
      ECOC containing particles, while Al_Silicate (including Al_Ca_Ti_Silicate,
      Al_Ti_Silicate, Al_Silicate) containing particles got higher fractions as size
      increase. The similarity of single particle mass spectrum signatures between two
      samples were studied by analyzing the dot product, results indicated that part of
      the single particle mass spectra of two samples in the same size range are
      similar, which bring challenge to the future source apportionment activity by
      using single particle aerosol mass spectrometer. Results of this study will
      provide physicochemical information of important sources which contribute to
      particle pollution, and will support source apportionment activities.

PMID- 28448927
TI  - Time-varying sensitivity analysis of hydrologic and sediment parameters at
      multiple timescales: Implications for conservation practices.
AB  - Environmental models can be used to better understand the hydrologic and sediment
      behavior in a watershed system. However, different processes may dominate at
      different time periods and timescales, which highly complicate the model
      interpretation. The related parameter uncertainty may be significant and needs to
      be addressed to avoid bias in the watershed management. In this study, we used
      the time-varying and multi-timescale (TVMT) method to characterize the temporal
      dynamics of parameter sensitivity at different timescales in hydrologic and
      sediment modeling. As a case study, the first order sensitivity indices were
      estimated with the Fourier amplitude sensitivity test (FAST) method for the
      Hydrological Simulation Program - Fortran (HSPF) model in the Zhangjiachong
      catchment in the Three Gorge Reservoir Region (TGRR) in China. The results were
      compared to those of the traditional aggregate method to demonstrate the merits
      of the TVMT method. The time-varying nature of the hydrologic and sediment
      parameters was revealed and explained mainly by the variation of hydro-climatic
      conditions. The baseflow recession parameter, evapotranspiration (ET) parameter
      for the soil storage, and sediment washoff parameter showed high sensitivities
      almost across the whole period. However, parameters related to canopy
      interception and channel sediment scour varied notably over time due to changes
      in the climate forcing. The timescale-dependent characteristics was observed and
      was most evident for the baseflow recession parameter and ET parameter. At last,
      the parameters affecting the sediment export and transport were discussed
      together with the inferred conservation practices. Reasonable controls for
      sediment must be storm-dependent. Compared to management practices on the land
      surface, practices affecting channel process would be more effective during storm
      events. Our results present one of the first investigations for sediment modeling
      in terms of the importance of parameter sensitivity in both time periods and
      evaluation timescales for the model calibration, diagnostic evaluation, and
      prioritizing efforts for conservation practices.

PMID- 28448928
TI  - Potential environmental impact of bioethanol production chain from fiber sorghum
      to be used in passenger cars.
AB  - A life cycle assessment (LCA) was applied to assess the environmental load of a
      prospective local bioethanol (EtOH) production system in Southern Italy by using
      lignocellulosic Fiber sorghum (FS) feedstock. A two steps analysis was carried
      out considering: (i) a "cradle-to-farm gate" LCA to investigate thoroughly the FS
      cultivation on hilly marginal land and (ii) a "cradle-to-wheels" system boundary
      encompassing the environmental pressure of the whole EtOH supply-use chain.
      Primary data related to lignocellulosic biomass production were combined with
      experimental feedstock conversion processes through advanced second generation
      technology. The purpose was the evaluation of the environmental performance of
      different EtOH-gasoline mixtures in midsize passenger cars: E10 (10% of EtOH and
      90% of gasoline) and E85 (85% of EtOH and 15% of gasoline). N fertilization
      appeared as the prevailing contributor of the crop phase. The "cradle-to-wheels"
      results concerning E10 passenger car disclosed that the main hotspots were
      represented by the input of low sulphur petrol (66%) and the linked tailpipe
      emissions (15%), for almost all the impact categories. Otherwise, for E85 flex
      fuel vehicle, the major drivers were represented by the feedstock production
      (46%) and the imported electricity used in the conversion facility (18%). The FS
      EtOH blends entailed potential environmental benefits compared with the fossil
      counterpart (gasoline) for climate change, ozone and fossil depletions.
      Otherwise, they evidenced a worse profile in terms of acidification,
      eutrophication and particulate matter formation. Within the context of a the
      prospective territorial bio-refinery network, the comparison of the annual FS
      bioethanol based systems with similar EtOH scenarios from giant reed perennial
      crops highlighted: (i) the importance to optimize the N-management for FS
      feedstock cultivation and (ii) the need to increase the use of the renewable
      energy carriers along the industrial conversion pathway.

PMID- 28448930
TI  - Determining equilibrium partition coefficients between lipid/protein and
      polydimethylsiloxane for highly hydrophobic organic contaminants using preloaded
      disks.
AB  - Bioaccumulation of hydrophobic organic contaminants is of great concern and
      understanding their partitioning to biological phases is crucial for estimating
      their bioaccumulation potential. The estimation, however, was of large
      uncertainty for highly hydrophobic organic contaminants (HHOCs) with log KOW>9
      due to the challenge of quantifying their water concentrations. In the present
      study, partition coefficients between polydimethylsiloxane (PDMS) and storage
      lipid (KSL,PDMS), membrane lipid (KML,PDMS) and protein (Kpro,PDMS) were measured
      for 21 polychlorinated biphenyls (PCBs), 14 polybrominated diphenyl ethers
      (PBDEs), dechlorane plus (DP) and decabromodiphenyl ethane (DBDPE), covering log
      KOW from 5.07 to 11.6, using a preloaded PDMS depletion method. The values of
      KSL,PDMS, KML,PDMS and Kpro,PDMS were in the ranges of 5.36-52.5, 0.286-11.8 and
      0.067-2.62g/g, respectively, being relatively constant although their KOW values
      extend more than six orders of magnitude. The relative sorption capacity of the
      biological phases showed storage lipid was the dominant sorption phase in biota,
      followed by membrane lipid and protein was the lowest. The KPDMS,pro values of
      the compounds with log KOW<9 were similar (0.382-14.9g/g) regardless of the
      thickness of preloaded PDMS disks (58-209MUm). For HHOCs, however, KPDMS,pro
      values dropped when thinner PDMS disks were used, as a result of slow diffusion
      of HHOCs in PDMS. The KPDMS,pro values of HHOCs measured by 58-MUm PDMS disks
      ranged from 1.78 to 6.85g/g, which was consistent with compounds with log KOW<9.
      This validated that partition coefficients between PDMS and biological phases
      were independent of chemical hydrophobicity, showing the advantage of using PDMS
      based methods to directly estimate bioaccumulation potential of HHOCs.

PMID- 28448929
TI  - Microbial use of low molecular weight DOM in filtered and unfiltered freshwater:
      Role of ultra-small microorganisms and implications for water quality monitoring.
AB  - Dissolved organic matter (DOM) plays a central role in regulating productivity
      and nutrient cycling in freshwaters. It is therefore vital that we can
      representatively sample and preserve DOM in freshwaters for subsequent analysis.
      Here we investigated the effect of filtration, temperature (5 and 25 degrees C)
      and acidification (HCl) on the persistence of low molecular weight (MW) dissolved
      organic carbon (DOC), nitrogen (DON) and orthophosphate in oligotrophic and
      eutrophic freshwater environments. Our results showed the rapid loss of
      isotopically-labelled glucose and amino acids from both filtered (0.22 and
      0.45MUm) and unfiltered waters. We ascribe this substrate depletion in filtered
      samples to the activity of ultra-small (<0.45MUm) microorganisms (bacteria and
      archaea) present in the water. As expected, the rate of C, N and P loss was much
      greater at higher temperatures and was repressed by the addition of HCl. Based on
      our results and an evaluation of the protocols used in recently published
      studies, we conclude that current techniques used to sample water for low MW DOM
      characterisation are frequently inadequate and lack proper validation. In
      contrast to the high degree of analytical precision and rigorous statistical
      analysis of most studies, we argue that insufficient consideration is still given
      to the presence of ultra-small microorganisms and potential changes that can
      occur in the low MW fraction of DOM prior to analysis.

PMID- 28448931
TI  - Tree growth-climate relationships in a forest-plot network on Mediterranean
      mountains.
AB  - In this study we analysed a novel tree-growth dataset, inferred from annual ring
      width measurements, of 7 forest tree species from 12 mountain regions in Greece,
      in order to identify tree growth - climate relationships. The tree species of
      interest were: Abies cephalonica, Abies borisii-regis, Picea abies, Pinus nigra,
      Pinus sylvestris, Fagus sylvatica and Quercus frainetto growing across a gradient
      of climate conditions with mean annual temperature ranging from 5.7 to 12.6
      degrees C and total annual precipitation from 500 to 950mm. In total, 344 tree
      cores (one per tree) were analysed across a network of 20 study sites. We found
      that water availability during the summer period (May-August) was a strong
      predictor of interannual variation in tree growth for all study species. Across
      species and sites, annual tree growth was positively related to summer season
      precipitation (PSP). The responsiveness of annual growth to PSP was tightly
      related to species and site specific measurements of instantaneous photosynthetic
      water use efficiency (WUE), suggesting that the growth of species with efficient
      water use is more responsive to variations in precipitation during the dry months
      of the year. Our findings support the importance of water availability for the
      growth of mountainous Mediterranean tree species and highlight that future
      reductions in precipitation are likely to lead to reduced tree-growth under
      climate change conditions.

PMID- 28448932
TI  - Seasonal changes of fructans in dimorphic roots of Ichthyothere terminalis
      (Spreng.) Blake (Asteraceae) growing in Cerrado.
AB  - Cerrado is a floristically rich savanna in Brazil, whose vegetation consists of a
      physiognomic mosaic, influenced by rainfall seasonality. In the dry season
      rainfall is substantially lower and reduces soil water supply, mainly for herbs
      and subshrubs. Climatic seasonal variations may well define phenological shifts
      and induce fluctuations of plant reserve pools. Some Cerrado native species have
      thickened underground organs that bear buds and store reserves, as adaptive
      features to enable plant survival following environmental stresses. Asteraceae
      species accumulate fructans in storage organs, which are not only reserve, but
      also protecting compounds against the effects of cold and drought. Ichthyothere
      terminalis is one Asteraceae species abundant in cerrado rupestre, with
      underground organs consisting of thickened orthogravitropic and diagravitropic
      roots. The objectives of this study were to analyze how abiotic environmental
      factors and plant phenology influence fructan dynamics in field grown plants, and
      verify if fructan metabolism differs in both root types for one year. I.
      terminalis accumulates inulin-type fructans in 10-40% of the dry mass in both
      root types. Fructan dynamics have similar patterns described for other Asteraceae
      species, exhibiting a proportional increase of polysaccharides with the
      senescence of the aerial organs. Multivariate analyzes showed that, as rainfall
      decreased, environmental factors had a stronger influence on metabolite levels
      than phenological shifts in both root types. Only slight differences were found
      in fructan dynamics between orthogravitropic and diagravitropic roots, suggesting
      they may have similar fructan metabolism regulation. However, these small
      differences may reflect distinct microclimatic conditions in both root types and
      also represent the influence of sink strength.

PMID- 28448933
TI  - In vitro bioaccessibility of copper azole following simulated dermal transfer
      from pressure-treated wood.
AB  - Micronized copper azole (MCA) and micronized copper quaternary (MCQ) are the
      latest wood preservatives to replace the liquid alkaline copper and chromated
      copper arsenate preservatives due to concerns over the toxicity or lack of
      effectiveness of the earlier formulations. Today, the use of MCA has become
      abundant in the wood preservative industry with approximately 38millionlbs of
      copper carbonate being used to treat lumber each year. Despite this widespread
      usage, little information is available on the bioaccessibility of this
      preservative upon gastrointestinal exposure. Using a simulated hand-to
      mouth/gastric system exposure study we investigated several types of commercially
      available copper-treated lumber products as-purchased and after exposure to
      outdoor weathering conditions. Soluble and particulate fractions of copper were
      measured after transfer to and release from surface wipes passed along copper
      treated lumber and exposed to synthetic stomach fluid (SSF, pH1.5) or deionized
      (DI) water. Wipes passed along new boards contained greater amounts of copper
      than wipes from weathered boards. The total copper recovered from the wipes after
      microwave extraction varied among the different wood types. For all wood types
      the copper released into SSF was more soluble than what was soluble in DI water.
      The data suggest that copper from treated wood is highly bioaccessible in SSF
      regardless of wood type and weathering condition.

PMID- 28448934
TI  - Release of dissolved phosphorus from riparian wetlands: Evidence for complex
      interactions among hydroclimate variability, topography and soil properties.
AB  - In agricultural landscapes, establishment of vegetated buffer zones in riparian
      wetlands (RWs) is promoted to decrease phosphorus (P) emissions because RWs can
      trap particulate P from upslope fields. However, long-term accumulation of P
      risks the release of dissolved P, since the unstable hydrological conditions in
      these zones may mobilize accumulated particulate P by transforming it into a
      mobile dissolved P species. This study evaluates how hydroclimate variability,
      topography and soil properties interact and influence this mobilization, using a
      three-year dataset of molybdate-reactive dissolved P (MRDP) and total dissolved P
      (TDP) concentrations in soil water from two RWs located in an agricultural
      catchment in western France (Kervidy-Naizin), along with stream P concentrations.
      Two main drivers of seasonal dissolved P release were identified: i) soil
      rewetting during water-table rise after dry periods and ii) reductive dissolution
      of soil Fe (hydr)oxides during prolonged water saturation periods. These
      mechanisms were shown to vary greatly in space (according to topography) and time
      (according to intra- and interannual hydroclimate variability). The concentration
      and speciation of the released dissolved P also varied spatially depending on
      soil chemistry and local topography. Comparison of sites revealed a similar
      correlation between soil P speciation (percentage of organic P ranging from 35
      70%) and the concentration and speciation of the released P (MRDP from <0.10 to
      0.40mgl-1; percentage of MRDP in TDP from 25-70%). These differences propagated
      to stream water, suggesting that the two RWs investigated were the main sources
      of dissolved P to streams. RWs can be critical areas due to their ability to
      biogeochemically transform the accumulated P in these zones into highly mobile
      and highly bioavailable dissolved P forms. Hydroclimate variability, local
      topography and soil chemistry must be considered to decrease the risk of
      remobilizing legacy soil P when establishing riparian buffer zones in
      agricultural landscapes.

PMID- 28448935
TI  - Analysis of the synoptic winter mortality climatology in five regions of England:
      Searching for evidence of weather signals.
AB  - Although heat-related mortality has received considerable research attention, the
      impact of cold weather on public health is less well-developed, probably due to
      the fact that physiological responses to cold weather can vary substantially
      among individuals, age groups, diseases etc., depending on a number of behavioral
      and physiological factors. In the current work we use the classification
      techniques provided by the COST-733 software to link synoptic circulation
      patterns with excess cold-related mortality in 5 regions of England. We conclude
      that, regardless of the classification scheme used, the most hazardous conditions
      for public health in England are associated with the prevalence of the Easterly
      type of weather, favoring advection of cold air from continental Europe. It is
      noteworthy that there has been observed little-to-no regional variation with
      regards to the classification results among the 5 regions, suggestive of a
      spatially homogenous response of mortality to the atmospheric patterns
      identified. In general, the 10 different groupings of days used reveal that
      excess winter mortality is linked with the lowest daily minimum/maximum
      temperatures in the area. However it is not uncommon to observe high mortality
      rates during days with higher, in relative terms, temperatures, when rapidly
      changing weather results in an increase of mortality. Such a finding confirms the
      complexity of cold-related mortality and highlights the importance of synoptic
      climatology in understanding of the phenomenon.

PMID- 28448937
TI  - Assessment of N2O emissions from a fertilised vegetable cropping soil under
      different plant residue management strategies using 15N tracing techniques.
AB  - Combined application of plant residues and N fertilisers strongly affect soil
      mineral N dynamics and N2O emissions depending on the quality of the plant
      residues, their application methods and other management strategies. We
      investigated the effect of combined application of two vegetable plant residues
      (cauliflower and sweet corn) and 15N fertiliser on N dynamics and N2O emission in
      a glasshouse pot study. The experiment was conducted under two residue management
      practices (soil incorporation vs surface mulching) over 98days with growing basil
      (Ocimum basilicum) plants. We also assessed the efficacy of applying the
      nitrification inhibitor, 3,4-dimethylpyrazole phosphate (DMPP) to the plant
      residues, for reducing N loss and mitigating N2O emissions. Application of plant
      residues, both on the soil surface or into soil, resulted in net N mineralisation
      and increased cumulative N2O emission compared with the application of N
      fertiliser alone. Soil surface mulching of sweet corn decreased total and residue
      induced cumulative N2O emission compared with the incorporation method, while it
      showed opposite effect on N2O emissions from cauliflower residue. The application
      of DMPP with sweet corn residue reduced total, residue- and fertiliser-induced
      N2O emissions; however its application with cauliflower residue did not show any
      mitigating effect on the N2O emissions. The residue application methods and the
      use of DMPP did not significantly affect 15N recovery by the basil plants. In
      contrast, soil incorporation of these residues doubled the microbial
      immobilisation of applied 15N into soil organic matter. Linear regression
      analysis of N2O emission during the experimental period indicated that in the
      treatments without DMPP application, soil NO3--N concentration was the most
      important factor in controlling the magnitude of N2O emissions, while the
      application of DMPP changed the dominant regulating factor from NO3--N to NH4+-N
      concentration.

PMID- 28448936
TI  - Composite of PAH-degrading endophytic bacteria reduces contamination and health
      risks caused by PAHs in vegetables.
AB  - Vegetables accumulate polycyclic aromatic hydrocarbons (PAHs) at high
      concentrations when grown in contaminated sites. Inoculation with PAH-degrading
      endophytic bacteria (EBPAH) has been recognized as one of the most promising ways
      to remove PAHs from plant bodies; however, the performance of single endophytic
      bacteria is generally limited. This investigation used a composite of eight EBPAH
      to reduce the contamination and health risk posed by 16 EPA priority PAHs in
      vegetables including Chinese cabbage (Brassica chinensis L.) and pakchoi
      (Brassica campestris L.). Composite EBPAH have strong PAH degradation abilities,
      and more than 65% of ?PAH were degraded after 10-day insuspension with composite
      EBPAH. Vegetable were contacted with composite EBPAH by seed soaking (SS) and
      leaf painting (LP) with an EBPAH cell incubation at OD600nm=0.2-1.5. Compared
      with those in non-inoculated controls, the ?PAH concentrations in edible parts of
      Chinese cabbage and pakchoi colonized by composite EBPAH via SS and LP with
      bacterial suspension at OD600nm=0.2-1.5 were 42.07-70.77% and 15.79-53.20% lower,
      and the incremental lifetime cancer risk (ILCR) values for males and females were
      31.78-84.08% and 26.60-83.40% smaller, respectively. SS was the optimal
      inoculation method for reducing PAH concentrations and ILCR values. Our results
      indicate that inoculating plants with composite EBPAH can lower the health risk
      posed by vegetables contaminated with PAHs, and may be used to mitigate plant PAH
      contamination.

PMID- 28448938
TI  - Choice modeling of system-wide or large scale environmental change in a
      developing country context: Lessons from the Paraiba do Sul River.
AB  - The Rio Paraiba do Sul is a highly polluted river in south central Brazil, that
      is contaminated by industrial, agricultural and municipal wastes, as well as
      being impacted by dams, water withdrawals and deforestation in the watershed.
      Since only very intensive and farreaching environmental policies could result in
      water quality improvements, valuing the restoration of the river presents many
      unique challenges. We develop a choice-modeling approach to valuation of the
      restoration of this river, with general tightening of environmental policy as the
      policy, and an increase in prices as the payment vehicle. The estimation is
      performed in willingness to pay space, adjusting for heterogeneity of tastes. We
      find that respondents, who are primarily low income, exhibit higher willingness
      to pay for complete restoration than moderate restoration, higher for moderate
      restoration in comparison to minimal restoration, and that they prefer
      restoration sooner, rather than later.

PMID- 28448939
TI  - Environmental impacts of producing bioethanol and biobased lactic acid from
      standalone and integrated biorefineries using a consequential and an
      attributional life cycle assessment approach.
AB  - This study evaluates the environmental impacts of biorefinery products using
      consequential (CLCA) and attributional (ALCA) life cycle assessment (LCA)
      approaches. Within ALCA, economic allocation method was used to distribute
      impacts among the main products and the coproducts, whereas within the CLCA
      system expansion was adopted to avoid allocation. The study seeks to answer the
      questions (i) what is the environmental impacts of process integration?, and (ii)
      do CLCA and ALCA lead to different conclusions when applied to biorefinery?.
      Three biorefinery systems were evaluated and compared: a standalone system
      producing bioethanol from winter wheat-straw (system A), a standalone system
      producing biobased lactic acid from alfalfa (system B), and an integrated
      biorefinery system (system C) combining the two standalone systems and producing
      both bioethanol and lactic acid. The synergy of the integration was the exchange
      of useful energy necessary for biomass processing in the two standalone systems.
      The systems were compared against a common reference flow: "1MJEtOH+1kgLA", which
      was set on the basis of products delivered by the system C. Function of the
      reference flow was to provide service of both fuel (bioethanol) at 99.9%
      concentration (wt. basis) and biochemical (biobased lactic acid) in food
      industries at 90% purity; both products delivered at biorefinery gate. The
      environmental impacts of interest were global warming potential (GWP100),
      eutrophication potential (EP), non-renewable energy (NRE) use and the
      agricultural land occupation (ALO). Regardless of the LCA approach adopted,
      system C performed better in most of the impact categories than both standalone
      systems. The process wise contribution to the obtained environmental impacts also
      showed similar impact pattern in both approaches. The study also highlighted that
      the recirculation of intermediate materials, e.g. C5 sugar to boost bioethanol
      yield and that the use of residual streams in the energy conversion were
      beneficial for optimizing the system performance.

PMID- 28448940
TI  - Modulation of CuO nanoparticles toxicity to green pea (Pisum sativum Fabaceae) by
      the phytohormone indole-3-acetic acid.
AB  - The response of plants to copper oxide nanoparticles (nano-CuO) in presence of
      exogenous phytohormones is unknown. In this study, green pea (Pisum sativum)
      plants were cultivated to full maturity in soil amended with nano-CuO (10-100nm,
      74.3% Cu), bulk-CuO (bCuO, 100-10,000nm, 79.7% Cu), and CuCl2 at 50 and 100mg/kg
      and indole-3-acetic acid (IAA) at 10 and 100MUM. Results showed that IAA at 10
      and 100MUM, averaged over all Cu treatments, reduced the number of plants by ~23%
      and ~34%, respectively. IAA at 10MUM, nano-CuO at 50mg/kg, b-CuO at 50mg/kg, and
      CuCl2 at 100mg/kg reduced pod biomass by about 50%. Although some combinations of
      IAA, mainly at 100MUM, with the Cu compounds altered nutrient accumulation in
      tissues, none of them affected pod elements. Conversely, without IAA, nano-CuO at
      50mg/kg, increased pod Fe and Ni by 258% and 325%, respectively, while bCuO at
      100mg/kg increased pod Ni by 275%, compared with control. With IAA at 10MUM, nano
      CuO (100mg/kg) and bCuO (50mg/kg) increased stem Cu by ~84% and ~78%. When IAA
      increased to 100MUM, nano-CuO and bCuO reduced stem Ca by 32% and 37%, and Mg by
      ~35%. Results suggest that both the nano-CuO and bCuO could improve the
      nutritional quality of pea pods, while exogenous IAA combined with Cu-based
      compounds could impact green pea production since these treatments reduced the
      number of plants and pod biomass.

PMID- 28448941
TI  - Geochemistry and microbial diversity of cave waters in the gypsum karst aquifers
      of Emilia Romagna region, Italy.
AB  - Fifty-seven control points of waters (sinking streams, rivers in caves, and
      resurgences) hosted in gypsum karst areas in Emilia Romagna region (N-Italy) were
      sampled in the framework of a Project LIFE+08NAT/IT/000369 "Gypsum" in the period
      2010-2014. The microbiology and chemistry of these waters have been analyzed to
      evaluate the impact of human activities or natural factors, in the gypsum karst
      systems. Waters have been analyzed for major chemistry (Ca, Mg, Na, K, SO4, HCO3,
      Cl, NO3) and some minor constituents (F, Br, NH4 and PO4), measuring pH, electric
      conductivity (EC), total dissolved solids (TDS) and temperature (T) in situ. The
      same samples have been analyzed with traditional microbiology techniques focused
      on total microbial count and on fecal microbiota, as index of human and/or animal
      contamination, and molecular biology techniques (sequencing of 16S rRNA segment
      and PCR-DGGE), focused on the characterization of microbial populations in the
      different sampling sites and determination of their variations and/or changes
      during the five years of the project. As expected, waters tend to be increasingly
      mineralized from sinking streams to resurgences, with only local and temporarily
      high contents in nitrates and ammonium, often related to the presence of bat
      colonies. PCR-DGGE revealed ecological changes, in terms of microbial populations
      present in the bulk water samples, in different sampling sites within the same
      cave. Although the impact of fecal microorganisms only rarely exceeded 2 log
      UFC/ml, the results evidenced fluctuations of these microorganisms mainly
      correlated to the season and to the biological activity of bats.

PMID- 28448942
TI  - Assessing knowledge of symptoms and first-aid care of epilepsy in Grenada, West
      Indies.
AB  - Epilepsy is a chronic neurological disorder that is increasingly prevalent in
      developing countries. It is critical to provide appropriate support to patients
      during seizures in order to prevent injuries. False beliefs regarding the
      etiology or pathogenesis of the epilepsy and inadequate health information may
      put patients with epilepsy or other seizure disorders at increased risk of
      injury. Our objective was to assess the level of epilepsy awareness amongst the
      general population in Grenada and educate the participants regarding proper first
      aid measures. A pilot questionnaire containing a total of 25 items surveying the
      knowledge, attitudes, and first-aid care of epilepsy was presented to 200 adult
      residents of Grenada as face-to-face interviews. Study participants were
      recruited over a nine-month period on a voluntary basis at health fairs, in local
      communities, and on the campus of St. George's University. Our results indicate
      that 35 out of 198 (17.7%) respondents erroneously believed that medicine should
      be placed in a person's mouth during a seizure, and 83 out of 200 (41.5%)
      answered that a person who is convulsing should be held down. Furthermore, 128
      out of 195 (65.6%) respondents erroneously believed that seizures occur when
      there is low brain activity and an additional 35 out of 199 (17.6%) regarded
      epilepsy as a contagious disorder. Our data suggest that persons with seizures
      and/or epilepsy may be at increased risk of injury in Grenada due to common
      misconceptions and false beliefs. It is critical that epilepsy awareness is
      promoted in developing countries, such as Grenada, where inadequate health
      information may be common.

PMID- 28448943
TI  - Mitochondria in endothelial cells: Sensors and integrators of environmental cues.
AB  - The involvement of angiogenesis in disease and its potential as a therapeutic
      target have been firmly established over recent decades. Endothelial cells (ECs)
      are central elements in vessel homeostasis and regulate the passage of material
      and cells into and out of the bloodstream. EC proliferation and migration are
      modified by alterations to mitochondrial biogenesis and dynamics resulting from
      several signals and environmental cues, such as oxygen, hemodynamics, and
      nutrients. As intermediary signals, mitochondrial ROS are released as important
      downstream modulators of the expression of angiogenesis-related genes. In this
      review, we discuss the physiological actions of these signals and aberrant
      responses during vascular disorders.

PMID- 28448944
TI  - Platelet cytochrome oxidase and citrate synthase activities in APOE epsilon4
      carrier and non-carrier Alzheimer's disease patients.
AB  - A degradation product of APOE epsilon4-encoded apolipoprotein E protein targets
      mitochondria and inhibits cytochrome oxidase (COX), and autopsy brains from young
      adult APOE epsilon4 carriers show reduced COX activity. To further explore
      relationships between APOE alleles and COX, we measured platelet mitochondria COX
      activity in AD subjects with (n=8) and without (n=7) an APOE epsilon4 allele and
      found the mean COX activity, when normalized to sample total protein, was lower
      in the APOE epsilon4 carriers (p<0.05). Normalizing COX activity to citrate
      synthase (CS) activity eliminated this difference, but notably the mean CS
      activity was itself lower in the APOE epsilon4 carriers (p<0.05). COX and CS
      protein levels did not appear to cause the lower APOE epsilon4 carrier COX and CS
      Vmax activities. If confirmed in larger studies, these data could suggest
      mitochondria at least partly mediate the well-recognized association between APOE
      alleles and AD risk.

PMID- 28448945
TI  - Teaching the basics of cancer metabolism: Developing antitumor strategies by
      exploiting the differences between normal and cancer cell metabolism.
AB  - This review of the basics of cancer metabolism focuses on exploiting the
      metabolic differences between normal and cancer cells. The first part of the
      review covers the different metabolic pathways utilized in normal cells to
      generate cellular energy, or ATP, and the glycolytic intermediates required to
      build the cellular machinery. The second part of the review discusses aerobic
      glycolysis, or the Warburg effect, and the metabolic reprogramming involving
      glycolysis, tricarboxylic acid cycle, and glutaminolysis in the context of
      developing targeted inhibitors in cancer cells. Finally, the selective targeting
      of cancer mitochondrial metabolism using positively charged lipophilic compounds
      as potential therapeutics and their ability to mitigate the toxic side effects of
      conventional chemotherapeutics in normal cells are discussed. I hope this
      graphical review will be useful in helping undergraduate, graduate, and medical
      students understand how investigating the basics of cancer cell metabolism could
      provide new insight in developing potentially new anticancer treatment
      strategies.

PMID- 28448946
TI  - Oral administration of methysticin improves cognitive deficits in a mouse model
      of Alzheimer's disease.
AB  - INTRODUCTION: There is increasing evidence for the involvement of chronic
      inflammation and oxidative stress in the pathogenesis of Alzheimer's disease
      (AD). Nuclear factor erythroid 2-related factor 2 (Nrf2) is an anti-inflammatory
      transcription factor that regulates the oxidative stress defense. Our previous
      experiments demonstrated that kavalactones protect neuronal cells against Amyloid
      beta (Abeta)-induced oxidative stress in vitro by Nrf2 pathway activation. Here,
      we tested an in vivo kavalactone treatment in a mouse model of AD. METHODS: The
      kavalactone methysticin was administered once a week for a period of 6 months to
      6 month old transgenic APP/Psen1 mice by oral gavage. Nrf2 pathway activation was
      measured by methysticin treatment of ARE-luciferase mice, by qPCR of Nrf2-target
      genes and immunohistochemical detection of Nrf2. Abeta burden was analyzed by
      CongoRed staining, immunofluorescent detection and ELISA. Neuroinflammation was
      assessed by immunohistochemical stainings for microglia and astrocytes. Pro
      inflammatory cytokines in the hippocampus was determined by Luminex multi-plex
      assays. The hippocampal oxidative damage was detected by oxyblot technique and
      immunohistochemical staining against DT3 and 4-HNE. The cognitive ability of mice
      was evaluated using Morris water maze. RESULTS: Methysticin treatment activated
      the Nrf2 pathway in the hippocampus and cortex of mice. The Abeta deposition in
      brains of methysticin-treated APP/Psen1 mice was not altered compared to
      untreated mice. However, methysticin treatment significantly reduced
      microgliosis, astrogliosis and secretion of the pro-inflammatory cytokines TNF
      alpha and IL-17A. In addition, the oxidative damage of hippocampi from APP/Psen1
      mice was reduced by methysticin treatment. Most importantly, methysticin
      treatment significantly attenuated the long-term memory decline of APP/Psen1
      mice. CONCLUSION: In summary, these findings show that methysticin administration
      activates the Nrf2 pathway and reduces neuroinflammation, hippocampal oxidative
      damage and memory loss in a mouse model of AD. Therefore, kavalactones might be
      suitable candidates to serve as lead compounds for the development of a new class
      of neuroprotective drugs.

PMID- 28448948
TI  - Interactions between the vascular endothelial growth factor gene polymorphism and
      life events in susceptibility to major depressive disorder in a Chinese
      population.
AB  - BACKGROUND: Recent studies suggest that vascular endothelial growth factor (VEGF)
      is involved in the development of major depressive disorder. The aim of this
      study is to investigate the interaction between vascular endothelial growth
      factor (VEGF) polymorphism (+405G/C, rs2010963) and negative life events in the
      pathogenesis of major depressive disorder (MDD). METHODS: DNA genotyping was
      performed on peripheral blood leukocytes in 274 patients with MDD and 273 age-and
      sex-matched controls. The frequency and severity of negative life events were
      assessed by the Life Events Scale (LES). A logistics method was employed to
      assess the gene-environment interaction (G*E). RESULTS: Differences in rs2010963
      genotype distributions were observed between MDD patients and controls.
      Significant G*E interactions between allelic variation of rs2010963 and negative
      life events were observed. Individuals carrying the C alleles were susceptible to
      MDD only when exposed to high-negative life events. CONCLUSIONS: These results
      indicate that interactions between the VEGF rs2010963 polymorphism and
      environment increases the risk of developing MDD.

PMID- 28448949
TI  - Utility of the Fitbit Flex to evaluate sleep in major depressive disorder: A
      comparison against polysomnography and wrist-worn actigraphy.
AB  - BACKGROUND: Sleep disturbance is a common and important component of affective
      illness. Fitness activity trackers are emerging as alternative means to estimate
      sleep in psychiatric patients; however, their ability to quantify sleep in mood
      disorders has not been empirically evaluated. Thus, this study sought to evaluate
      the utility of the Fitbit Flex (FBF) to estimate sleep in patients with major
      depressive disorder (MDD) relative to gold standard polysomnography (PSG) and a
      widely-used actigraph (Actiwatch-2; AW-2). METHODS: Twenty-one patients with
      unipolar MDD wore the FBF and AW-2 during in-laboratory PSG. Bland-Altman
      analysis compared sleep variables among devices. Epoch-by-epoch analysis further
      evaluated sensitivity, specificity, and accuracy for the FBF and AW-2 relative to
      PSG. RESULTS: The FBF demonstrated significant limitations in quantifying sleep
      and wake, relative to PSG. In the normal setting, the FBF significantly
      overestimated sleep time and efficiency, and displayed poor ability to correctly
      identify wake epochs (i.e. low specificity). In the sensitive setting, the FBF
      significantly underestimated sleep time and efficiency relative to PSG.
      Performance characteristics of the FBF were more similar to the AW-2 in the
      normal compared to sensitive setting. LIMITATIONS: Participants were young to
      middle aged and predominantly female, which may limit generalizability of
      findings. Study design also precluded ability to assess longitudinal performance
      of FBF. CONCLUSIONS: The FBF is not an adequate substitute for PSG when
      quantifying sleep in MDD, and the settings of the device sizably impact its
      performance relative to PSG and other standard actigraphs. The limitations and
      capabilities of the FBF should be carefully considered prior to clinical and
      research implementation.

PMID- 28448950
TI  - Promoting innovation in small markets: Evidence from the market for rare and
      intractable diseases.
AB  - In many medical care markets with limited profit potential, firms often have
      little incentive to innovate. These include the market for rare diseases,
      "neglected" tropical diseases, and personalized medicine. Governments and not-for
      profit organizations promote innovation in such markets but empirical evidence on
      the policy effect is limited. We study this issue by analyzing the impact of a
      demand-side policy in Japan, which reduces the cost sharing of patients with some
      rare and intractable diseases and attempts to establish and promote the treatment
      of those diseases. Using clinical trials data taken from public registries, we
      identify the effect of the policy using a difference-in-difference approach. We
      find that the demand-side policy increased firms' incentive to innovate: firm
      sponsored clinical trials increased 181% (0.16 per disease per year) when covered
      by the policy. This result indicates that the demand-side policy can be an
      important part of innovation policies in markets with limited profit potential.

PMID- 28448947
TI  - Traveling from the hypothalamus to the adipose tissue: The thermogenic pathway.
AB  - Brown adipose tissue (BAT) is a specialized tissue critical for non-shivering
      thermogenesis producing heat through mitochondrial uncoupling; whereas white
      adipose tissue (WAT) is responsible of energy storage in the form of
      triglycerides. Another type of fat has been described, the beige adipose tissue;
      this tissue emerges in existing WAT depots but with thermogenic ability, a
      phenomenon known as browning. Several peripheral signals relaying information
      about energy status act in the brain, particularly the hypothalamus, to regulate
      thermogenesis in BAT and browning of WAT. Different hypothalamic areas have the
      capacity to regulate the thermogenic process in brown and beige adipocytes
      through the sympathetic nervous system (SNS). This review discusses important
      concepts and discoveries about the central control of thermogenesis as a trip
      that starts in the hypothalamus, and taking the sympathetic roads to reach brown
      and beige fat to modulate thermogenic functions.

PMID- 28448951
TI  - Neuromuscular blockade requirement is associated with good neurologic outcome in
      cardiac arrest survivors treated with targeted temperature management.
AB  - PURPOSE: We examined the association between neuromuscular blockade (NMB)
      requirements and outcomes and lactate clearance in cardiac arrest survivors
      treated with targeted temperature management (TTM). METHODS: We included
      consecutive adult cardiac arrest survivors treated with TTM between 2012 and
      2015. NMB use was categorized into 3 groups: no NMB, bolus NMB (intermittent
      bolus use), and continuous NMB (continuous infusion). Serum lactate levels were
      measured on admission and at 12h, 24h, and 48h after admission. The primary
      outcome was neurologic outcome at discharge. The secondary outcomes were in
      hospital mortality and lactate clearance. RESULTS: In total, 309 patients were
      included. Of these, 206 (66.7%) and 73 (23.6%) were discharged with poor
      neurologic outcome and death, respectively. Multivariate analysis revealed that
      continuous NMB, as opposed to no NMB use, was associated with decreased poor
      neurologic outcomes (odds ratio [OR], 0.317; 95% confidence interval [CI], 0.124
      0.815) and decreased in-hospital mortality (OR, 0.414; 95% CI, 0.183-0.941).
      There were no differences in lactate clearance between the NMB groups.
      CONCLUSION: Continuous NMB requirement was associated with improved neurologic
      outcome and decreased in-hospital mortality in cardiac arrest survivors treated
      with TTM. The NMB requirement was not associated with lactate clearance.

PMID- 28448952
TI  - Sepsis and septic shock: Pathogenesis and treatment perspectives.
AB  - The majority of bacteremias do not develop to sepsis: bacteria are cleared from
      the bloodstream. Oxygen released from erythrocytes and humoral immunity kill
      bacteria in the bloodstream. Sepsis develops if bacteria are resistant to
      oxidation and proliferate in erythrocytes. Bacteria provoke oxygen release from
      erythrocytes to arterial blood. Abundant release of oxygen to the plasma triggers
      a cascade of events that cause: 1. oxygen delivery failure to cells; 2. oxidation
      of plasma components that impairs humoral regulation and inactivates immune
      complexes; 3. disseminated intravascular coagulation and multiple organs'
      failure. Bacterial reservoir inside erythrocytes provides the long-term survival
      of bacteria and is the cause of ineffectiveness of antibiotics and host immune
      reactions. Treatment perspectives that include different aspects of sepsis
      development are discussed.

PMID- 28448953
TI  - Electrostatic frequency maps for amide-I mode of beta-peptide: Comparison of
      molecular mechanics force field and DFT calculations.
AB  - The spectroscopy of amide-I vibrations has been widely utilized for the
      understanding of dynamical structure of polypeptides. For the modeling of amide-I
      spectra, two frequency maps were built for beta-peptide analogue (N
      ethylpropionamide, NEPA) in a number of solvents within different schemes
      (molecular mechanics force field based, GM map; DFT calculation based, GD map),
      respectively. The electrostatic potentials on the amide unit that originated from
      solvents and peptide backbone were correlated to the amide-I frequency shift from
      gas phase to solution phase during map parameterization. GM map is easier to
      construct with negligible computational cost since the frequency calculations for
      the samples are purely based on force field, while GD map utilizes sophisticated
      DFT calculations on the representative solute-solvent clusters and brings insight
      into the electronic structures of solvated NEPA and its chemical environments.
      The results show that the maps' predicted amide-I frequencies present solvation
      environmental sensitivities and exhibit their specific characters with respect to
      the map protocols, and the obtained vibrational parameters are in satisfactory
      agreement with experimental amide-I spectra of NEPA in solution phase. Although
      different theoretical schemes based maps have their advantages and disadvantages,
      the present maps show their potentials in interpreting the amide-I spectra for
      beta-peptides, respectively.

PMID- 28448954
TI  - Copper complexes containing thiosemicarbazones derived from 6-nitropiperonal:
      Antimicrobial and biophysical properties.
AB  - A series of four thiosemicarbazones from 6-nitropiperonal along with the
      corresponding copper complexes were synthesized. The biophysical characteristics
      of the complexes were investigated by the binding to DNA and human serum albumin.
      The binding to DNA is moderate; the binding constants run from (0.49-7.50)*104M
      1. In relation to HSA, the complexes interact strongly with binding constants on
      the order of 105M-1. The complexes also display antioxidant behavior as
      determined by the ability to scavenge diphenylpicrylhydrazyl (dpph) and nitric
      oxide radicals. The antimicrobial profiles of the compounds, tested against a
      panel of microbes including five of the ESKAPE pathogens (Staphylococcus aureus,
      MRSA, Escherichia coli, Klebsiella pneumoniae, MDR, Acinetobacter baumannii,
      Pseudomonas aeruginosa) and two yeasts (Candida albicans and Cryptococcus
      neoformans var. grubii), are also described. The compounds contain a core moiety
      that is similar to oxolinic acid, a quinolone antibiotic that targets DNA gyrase
      and topoisomerase (IV). The binding interaction between the complexes and these
      important antibacterial targets were studied by computational methods, chiefly
      docking studies. The calculated dissociation constants for the interaction with
      DNA gyrase B (from Staphylococcus aureus) range from 4.32 to 24.65MUM; the
      binding was much stronger to topoisomerase IV, with dissociation constants
      ranging from 0.37 to 1.27MUM.

PMID- 28448955
TI  - Ionization spectroscopies and theoretical calculations of cis and trans 3-fluoro
      N-methylaniline-Arn(n=1,2) van der Waals clusters: Structures and binding
      energies.
AB  - The ab initio and dispersion-corrected density functional theory (DFT)
      calculations of the van der Waals (vdW) clusters of cis and trans 3-fluoro-N
      methylaniline-Arn (3FNMA-Arn) (n=1,2) predict that, for cis and trans 3FNMA-Ar1
      clusters, the pi-bound geometry with the Ar atom sitting over the ring is the
      global minimum in both neutral and cationic states, while for cis and trans 3FNMA
      Ar2 clusters, the [pi|pi]-bound sandwich structure with two Ar ligands occupying
      nearly equivalent pi-bound positions above and below the ring plane is the global
      minimum. The vibronic spectra of cis and trans 3FNMA-Ar1 clusters in the S1 state
      were recorded by using one-color and two-color resonant two-photon ionization
      (R2PI) techniques, the comparison of which yields an estimate of the binding
      energy of cluster in the S1 state. It is found that the linear correlation
      between the redshift of the S1<-S0 electronic transition energy (E1) of cluster
      and the E1 of the monomer also holds for the Ar clusters of hetero-di-substituted
      aromatics. By recording the photoionization efficiency (PIE) curves and mass
      analyzed threshold ionization (MATI) dissociation spectra of cis and trans 3FNMA
      Ar1 clusters, the ionization energies (IE) and binding energies of clusters in
      the D0 state are obtained. The MATI spectra of the cis and trans 3FNMA-Ar1
      cations exhibit significant progressions of the vdW bending mode (bx), indicating
      the structural changes of the clusters in the bending coordinate upon ionization.
      The combination of the three kinds of spectroscopic methods provides the binding
      energies of cis and trans 3FNMA-Ar1 clusters in the S0, S1 and D0 states with
      good accuracy, and the values estimated by dispersion-corrected DFT calculations
      compare well with the experimental results. From our studies, the omegaB97X-D and
      TD-omegaB97X-D methods using high quality basis set are recommended for studying
      the intermolecular interaction of such vdW clusters in the ground and excited
      states.

PMID- 28448956
TI  - Concentration dependent switch in the kinetic pathway of lysozyme fibrillation:
      Spectroscopic and microscopic analysis.
AB  - Formation of amyloid fibrils is found to be a general tendency of many proteins.
      Investigating the kinetic mechanisms and structural features of the intermediates
      and the final fibrillar state is essential to understand their role in amyloid
      diseases. Lysozyme, a notable model protein for amyloidogenic studies, readily
      formed fibrils in vitro at neutral pH in the presence of urea. It, however,
      showed two different kinetic pathways under varying urea concentrations when
      probed with thioflavin T (ThT) fluorescence. In 2M urea, lysozyme followed a
      nucleation-dependent fibril formation pathway which was not altered by varying
      the protein concentration from 2mg/ml to 8mg/ml. In 4M urea, the protein
      exhibited concentration dependent change in the mechanism. At lower protein
      concentrations, lysozyme formed fibrils without any detectable nuclei (nucleation
      independent polymerization pathway). When the concentration of the protein was
      increased above 3mg/ml, the protein followed nucleation-dependent polymerization
      pathway as observed in the case of 2M urea condition. This was further verified
      using microscopic images of the fibrils. The kinetic parameters such as lag time,
      elongation rate, and fibrillation half-time, which were derived from ThT
      fluorescence changes, showed linear dependency against the initial protein
      concentration suggested that under the nucleation-dependent pathway conditions,
      the protein followed primary-nucleation mechanism without any significant
      secondary nucleation events. The results also suggested that the differences in
      the initial protein conformation might alter the mechanism of fibrillation;
      however, at the higher protein concentrations lysozyme shifted to nucleation
      dependent pathway.

PMID- 28448957
TI  - Static vs dynamic DFT prediction of IR spectra of flexible molecules in the
      condensed phase: The (ClCF2CF(CF3)OCF2CH3) liquid as a test case.
AB  - First-principles molecular dynamics (FPMD) simulations in the framework of
      Density Functional Theory (DFT) are carried out for the prediction of the
      infrared spectrum of the fluorinated molecule ClCF2CF(CF3)OCF2CH3 in liquid and
      gas phase. This molecule is characterized by a flexible structure, allowing the
      co-existence of several stable conformers, that differ by values of the torsional
      angles. FPMD computed spectra are compared to the experimental ones, and to
      Boltzmann weighted IR spectra based on gas phase calculations.

PMID- 28448958
TI  - Evaluation of F8-TNF-alpha in Models of Early and Progressive Metastatic
      Osteosarcoma.
AB  - The targeted delivery of tumor necrosis factor-alpha (TNF-alpha) with antibodies
      specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra
      domain A (EDA) domain of fibronectin] has already shown efficacy against
      experimental sarcomas but has not yet been investigated in orthotopic sarcomas.
      Here, we investigated F8-TNF in a syngeneic K7 M2-derived orthotopic model of
      osteosarcoma as a treatment against pulmonary metastases, the most frequent cause
      of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue
      confirmed the presence of EDA in primary tumors (PTs) as well as metastases. In
      mice, the efficacy of F8-TNF against PTs and early pulmonary metastases was
      evaluated. Intratibial PT growth was not affected by F8-TNF, yet early
      micrometastases were reduced possibly due to an F8-TNF-dependent attraction of
      pulmonary CD4+, CD8+, and natural killer cells. Furthermore, immunofluorescence
      revealed stronger expression of EDA in early pulmonary metastases compared with
      PT tissue. To study progressing pulmonary metastases, a hind limb amputation
      model was established, and the efficacy of F8-TNF, alone or combined with
      doxorubicin, was investigated. Despite the presence of EDA in metastases, no
      inhibition of progressive metastatic growth was detected. No significant
      differences in numbers of CD4+ or CD8+ cells or F4/80+ and Ly6G+ myeloid-derived
      cells were observed, although a strong association between metastatic growth and
      presence of pulmonary Ly6G+ myeloid-derived cells was detected. In summary, these
      findings demonstrate the potential of F8-TNF in activating the immune system and
      reducing early metastatic growth yet suggest a lack of efficacy of F8-TNF alone
      or combined with doxorubicin against progressing osteosarcoma metastases.

PMID- 28448959
TI  - Detection of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric
      Cancer.
AB  - PURPOSE: Gastric cancer studies indicated a potential correlation between
      circulating tumor cells (CTCs) in peripheral blood and tumor relapse/metastasis.
      The prevalence and significance of circulating tumor microemboli (CTM) in gastric
      cancer remain unknown. We investigated the prevalence and prognostic value of
      CTCs and CTM for progression-free survival (PFS) and overall survival (OS) in
      gastric cancer patients. METHODS: Eighty-one gastric cancer patients consented to
      provide 5ml of peripheral blood before systematic therapy. CTCs and CTM were
      isolated using isolation by size of epithelial tumor cells and characterized by
      cytopathologists. For 41 stage IV gastric cancer patients, CTM was investigated
      as a potential biomarker to predict prognosis. RESULTS: CTCs were detected in 51
      patients; the average count was 1.81. In clinical stage I, II, III, and IV
      patients, the average CTC counts were 1.40, 0.67, 1.24, and 2.71, respectively.
      CTM were detected in 3 of 33 clinical stage I to IIIb patients, at an average of
      0.12 (0-2). CTM were detected in 13 of 53 clinical stage IIIc to IV patients, at
      an average of 1.26 (0-22). In stage IV patients, CTM positivity correlated with
      the CA125 level. PFS and OS in CTM-positive patients were significantly lower
      than in CTM-negative patients (P<.001). CTM positivity was an independent factor
      for determining the PFS (P=.016) and OS (P=.003) of stage IV patients in
      multivariate analysis. Using markers of the epithelial-mesenchymal transition,
      single CTCs were divided into three phenotypes including epithelial CTCs,
      biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs. For CTM, CK
      /Vimentin+/CD45- and CK+/Vimentin+/CD45- phenotypes were observed, but the
      CK+/Vimentin-/CD45- CTM phenotype was not. CA125 was detected in gastric cancer
      cell lines BGC823 and MGC803. CONCLUSIONS: In stage IV patients, CTM positivity
      was correlated with serum CA125 level. CTM were an independent predictor of
      shorter PFS and OS in stage IV patients. Thus, CTM detection may be a useful tool
      to predict prognosis in stage IV patients.

PMID- 28448960
TI  - Utility of Genomic Analysis in Differentiating Synchronous and Metachronous Lung
      Adenocarcinomas from Primary Adenocarcinomas with Intrapulmonary Metastasis.
AB  - Distinguishing synchronous and metachronous primary lung adenocarcinomas from
      adenocarcinomas with intrapulmonary metastasis is essential for optimal patient
      management. In this study, multiple lung adenocarcinomas occurring in the same
      patient were evaluated using comprehensive histopathologic evaluation
      supplemented with molecular analysis. The cohort included 18 patients with a
      total of 52 lung adenocarcinomas. Eleven patients had a new diagnosis of multiple
      adenocarcinomas in the same lobe (n=5) or different lobe (n=6). Seven patients
      had a history of lung cancer and developed multiple new tumors. The final
      diagnosis was made in resection specimens (n=49), fine needle aspiration (n=2),
      and biopsy (n=1). Adenocarcinomas were non-mucinous, and histopathologic
      comparison of tumors was performed. All tumors save for one were subjected to ALK
      gene rearrangement testing and targeted Next Generation Sequencing (NGS). Using
      clinical, radiologic, and morphologic features, a confident conclusion favoring
      synchronous/metachronous or metastatic disease was made in 65% of patients. Cases
      that proved challenging included ones with more than three tumors showing
      overlapping growth patterns and lacking a predominant lepidic component. Genomic
      signatures unique to each tumor were helpful in determining the relationship of
      multiple carcinomas in 72% of patients. Collectively, morphologic and genomic
      data proved to be of greater value and achieved a conclusive diagnosis in 94% of
      patients. Assessment of the genomic profiles of multiple lung adenocarcinomas
      complements the histological findings, enabling a more comprehensive assessment
      of synchronous, metachronous, and metastatic lesions in most patients, thereby
      improving staging accuracy. Targeted NGS can identify genetic alterations with
      therapeutic implications.

PMID- 28448961
TI  - Supported binary liposome vesicle-gold nanoparticle for enhanced label free DNA
      and protein sensing.
AB  - Supported binary liposome mixture of cationic liposome N-[1-(2,3
      Dioleoyloxy)propyl]-N,N,N-trimethylammonium propane (DOTAP) and the zwitterionic
      liposome 1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine (DOPE) were tethered on
      thiol monolayers in the absence and presence of gold nanoparticle to enhance
      sensor stability and sensitivity for label free DNA and protein sensing for the
      first time. Cysteamine hydrochloride (Cyst), 3-Mercaptopropionic acid (MPA), 11
      Mercaptoundecanoic acid (MUDA) and 11-amino-1-undecane thiol (AUT) monolayers
      were used as tethers on gold surfaces. Electrochemical studies in the presence of
      [Fe(CN)6]3-/4- indicate that the presence of both DOPE and AuNP decreases the
      electrostatic interaction between DOTAP and MPA layer during the formation of
      DOPE-DOTAP-AuNP (DDA) whereas they enhance the repulsive force on the Cyst and
      AUT monolayers. In the thiol monolayer supported DDA, the gelation of neutral
      lipid DOPE by the AuNP is disfavored which inturn promotes stability of vesicle
      structure. The membrane protein melittin's interaction with the DDA indicates the
      presence of intact vesicle by showing decreased charge transfer for the MUDA and
      AUT in the presence of [Fe(CN)6]3-/4-. On the contrary, the presence of the
      bilayer and semi circled DDA on the MPA and cysteamine layers were confirmed by
      the increased redox reaction. Atomic Force Microscopic (AFM) and Transmission
      Electron Microscopic (TEM) images support the presence of an array like semi
      circled DDA on the MPA and well separated DDA vesicles on the MUDA with variable
      sizes. Dynamic Light Scattering (DLS) and Fourier Transform Infrared spectroscopy
      (FTIR) suggest effective coordination between DOPE, DOTAP and AuNP. Label free
      DNA hybridization sensing in presence of the negatively charged [Fe(CN)6]3-/4-
      indicates the lowest DNA detection limit of 1*10-14M with linearity range 1*10-13
      to 1*10-9M. Similarly, streptavidin sensing shows the lowest detection of 1ngml-1
      with a linear range 100ng to 1ug due to the increased reactive sites and
      distance.

PMID- 28448962
TI  - Progressive changes in non-coding RNA profile in leucocytes with age.
AB  - It has been observed that immune cell deterioration occurs in the elderly, as
      well as a chronic low-grade inflammation called inflammaging. These cellular
      changes must be driven by numerous changes in gene expression and in fact, both
      protein-coding and non-coding RNA expression alterations have been observed in
      peripheral blood mononuclear cells from elder people. In the present work we have
      studied the expression of small non-coding RNA (microRNA and small nucleolar RNA 
      snoRNA-) from healthy individuals from 24 to 79 years old. We have observed that
      the expression of 69 non-coding RNAs (56 microRNAs and 13 snoRNAs) changes
      progressively with chronological age. According to our results, the age range
      from 47 to 54 is critical given that it is the period when the expression trend
      (increasing or decreasing) of age-related small non-coding RNAs is more
      pronounced. Furthermore, age-related miRNAs regulate genes that are involved in
      immune, cell cycle and cancer-related processes, which had already been
      associated to human aging. Therefore, human aging could be studied as a result of
      progressive molecular changes, and different age ranges should be analysed to
      cover the whole aging process.

PMID- 28448963
TI  - Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young
      age.
AB  - Combination antiretroviral therapies (cART)can lead to normal life expectancy in
      HIV-infected persons, and people aged >50 yrs represent the fastest growing HIV
      group. Although HIV and aging are independently associated with impaired humoral
      immunity, immune status in people aging with HIV is relatively unexplored. In
      this study influenza vaccination was used to probe age associated perturbations
      in the B cell compartment of HIV-negative "healthy controls" (HC) and
      virologically controlled HIV-infected participants on cART (HIV) (n=124), grouped
      by age as young (<40 yrs), middle-aged (40-59yrs) or old (>60 yrs). H1N1 antibody
      response at d21 post-vaccination correlated inversely with age in both HC and
      HIV. Immunophenotyping of cryopreserved PBMC demonstrated increased frequencies
      of double negative B cells and decreased plasmablasts in old compared to young
      HC. Remarkably, young HIV were different from young HC but similar to old HC in B
      cell phenotype, influenza specific spontaneous (d7) or memory (d21) antibody
      secreting cells. We conclude that B cell immune senescence is a prominent
      phenomenon in young HIV in comparison to young HC, but distinctions between old
      HIV and old HC are less evident though both groups manifest age-associated B cell
      dysfunction.

PMID- 28448964
TI  - Antioxidant and Hepatoprotective Effect of Swertiamarin on Carbon Tetrachloride
      Induced Hepatotoxicity via the Nrf2/HO-1 Pathway.
AB  - BACKGROUND/AIMS: Swertiamarin (STM), the main bioactive component in Swertia
      mussotii Franch (Gentianaceae), has been shown to exert hepatoprotective effects
      on experimental liver injury. However, the effects and exact mechanisms of STM on
      carbon tetrachloride (CCl4) causing hepatotoxicity are still unknown. This study
      investigated the potential protective effects and mechanisms of STM on CCl4
      induced liver injury in rats. METHODS: Adult male Sprague-Dawley (SD) rats were
      exposed to CCl4 with or without STM co-administration for consecutive eight
      weeks. RESULTS: STM significantly ameliorated CCl4-induced increase in serum
      alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline
      phosphatase (ALP) levels and histopathological changes in the liver. Hepatic
      oxidative stress was repressed by STM, as evidenced by the decrease in
      malondialdehyde (MDA), with concomitant increase in antioxidase activity (e.g.
      superoxide dismutase (SOD); glutathione peroxidase (GPx)), glutathione (GSH)
      level. STM also obviously attenuated inflammatory response in CCl4-lesioned
      livers as evidenced by the decrease in inflammatory cytokines/ chemokines (e.g.
      inducible nitric oxide synthase (iNOS), interleukin-1beta (IL-1beta)).
      Additionally, STM significantly induced the expression of CYPs, efflux
      transporters and PDZK1 as compared with the CCl4 group. Moreover, co
      administration of STM with CCl4 remarkably up-regulated the expression of Nrf2,
      HO-1 and NQO1 compared with the CCl4 group. CONCLUSIONS: The present study
      demonstrates that STM exerts a protective effect against CCl4-induced liver
      injury and inflammation with its antioxidant effects and induction of hepatic
      detoxification enzymes and efflux transporters expression, at least in part, via
      the Nrf2/HO-1 pathway in rats.

PMID- 28448965
TI  - Neuroprotective Treatments after Perinatal Hypoxic-Ischemic Brain Injury
      Evaluated with Magnetic Resonance Spectroscopy.
AB  - Perinatal hypoxic-ischemic brain injury is a major health problem. Adjuvant
      treatments that improve the neuroprotective effect of the current treatment,
      therapeutic hypothermia, are urgently needed. The growing knowledge about the
      complex pathophysiology of hypoxia-ischemia (HI) has led to the discovery of
      several important targets for neuroprotection. Early interventions should focus
      on the preservation of energy metabolism, the reduction of glutamate
      excitotoxicity and oxidative stress, the maintenance of calcium homeostasis, and
      the prevention of apoptosis. Delayed interventions should promote injury repair.
      The multiple metabolic changes following HI as well as the metabolic effects of
      potential treatments can be observed noninvasively by magnetic resonance
      spectroscopy (MRS). This mini-review provides an overview of the neuroprotective
      pharmacological agents that have been evaluated with 1H/31P/13C MRS. A better
      understanding of how these agents influence cerebral metabolism and the use of
      relevant translational MRS biomarkers can guide future clinical trials.

PMID- 28448966
TI  - Peritoneal Dialysis as the Dialysis Initial Modality of Choice for Renal
      Replacement Therapy Initiation: Moving from "Why" to "Why Not".

PMID- 28448967
TI  - PharmaNews.

PMID- 28448968
TI  - Changing Epidemiological Patterns in Traumatic Brain Injury: A Longitudinal
      Hospital-Based Study in Belgium.
AB  - BACKGROUND: Various reports have suggested that epidemiological patterns of
      Traumatic Brain Injury (TBI) are changing in high-income countries, but the
      evidence to support this is often indirect and only a few longitudinal studies
      exist. We aimed to explore epidemiological patterns of TBI in Belgium over a 10
      year period. METHODS: A retrospective analysis of Minimum Hospital Data provided
      by Statistics Belgium was performed for the period 2003-2012. ICD-9
      classification was used to identify TBI and to differentiate subtypes. The annual
      incidence of hospital admissions and in-hospital mortality rates were calculated
      and further differentiated for age, gender and cause of injury. RESULTS: The age
      adjusted incidence of hospital admissions decreased by 3.6% per year. An increase
      in the number of elderly patients with TBI and a decrease in the younger age
      groups were found. Falls now represent the main cause of TBI. A mortality rate of
      6.5 per 100,000 population per year was found and did not change significantly
      over time. CONCLUSIONS: This longitudinal study confirms that epidemiological
      patterns in TBI are changing: overall incidence is steadily decreasing, but in
      elderly patients, the incidence is increasing. Falls are the leading cause,
      occurring most frequently in elderly patients. These changes are relevant for
      prevention.

PMID- 28448970
TI  - Editorial Board / Contents / Imprint.

PMID- 28448969
TI  - Synthetic, Switchable Enzymes.
AB  - The construction of switchable, radiation-controlled, aptameric enzymes -
      "swenzymes" - is, in principle, feasible. We propose a strategy to make such
      catalysts from 2 (or more) aptamers each selected to bind specifically to one of
      the substrates in, for example, a 2-substrate reaction. Construction of a
      combinatorial library of candidate swenzymes entails selecting a set of a million
      aptamers that bind one substrate and a second set of a million aptamers that bind
      the second substrate; the aptamers in these sets are then linked pairwise by a
      linker, thus bringing together the substrates. In the presence of the substrates,
      some linked aptamer pairs catalyze the reaction when exposed to external energy
      in the form of a specific frequency of low-intensity, nonionizing electromagnetic
      or acoustic radiation. Such swenzymes are detected via a separate product
      capturing aptamer that changes conformation on capturing the product; this
      altered conformation allows it (1) to bind to every potential swenzyme in its
      vicinity (thereby giving a higher probability of capture to the swenzymes that
      generate the product) and (2) to bind to a sequence on a magnetic bead (thereby
      permitting purification of the swenzyme plus product-capturing aptamer by
      precipitation). Attempts to implement the swenzyme strategy may help elucidate
      fundamental problems in enzyme catalysis.

PMID- 28448971
TI  - Pre-ESRD Dementia and Post-ESRD Mortality in a Large Cohort of Incident Dialysis
      Patients.
AB  - BACKGROUND: Conservative management may be a desirable option for elderly,
      fragile, or demented patients who reach end-stage renal disease (ESRD), yet some
      patients with dementia are placed on renal replacement therapy nonetheless.
      METHODS: From a nationwide cohort of 45,076 US veterans who transitioned to ESRD
      over 4 contemporary years (October 1, 2007 to September 30, 2011), we identified
      1,336 (3.0%) patients with International Classification of Diseases, Ninth
      Revision, Clinical Modification code-based dementia diagnosis during the prelude
      (predialysis) period. We examined the association of prelude dementia with all
      cause mortality within the first 6 months following transition to dialysis, using
      a propensity-matched cohort and Cox proportional hazards models. RESULTS: In the
      entire cohort, the overall mean +/- standard deviation age at baseline was 72 +/-
      11 years, 95% were male, 23% were African-American, and 66% were diabetic. There
      were 8,080 (18.5%) deaths (mortality rate, 412; 95% confidence interval [CI], 403
      421/1,000 patient-years) in the dementia-negative group, and 396 (29.6%) deaths
      (mortality rate, 708; 95% CI, 642-782/1,000 patient-years) in the dementia
      positive group in the entire cohort in the first 6 months after dialysis
      initiation. Presence of dementia was associated with higher risk of all-cause
      mortality (adjusted hazard ratio, 1.25; 95% CI, 1.12-1.38) compared to dementia
      free patients in the first 6 months after dialysis initiation. CONCLUSION: Pre
      ESRD dementia is associated with increased risk of early post-ESRD mortality in
      veterans transitioning to dialysis.

PMID- 28448972
TI  - Science, Innovation and the Future of Humanity.

PMID- 28448973
TI  - Downregulations of CD36 and Calpain-1, Inflammation, and Atherosclerosis by
      Simvastatin in Apolipoprotein E Knockout Mice.
AB  - BACKGROUND: In the previous in vitro study, we found that simvastatin decreased
      the protein expression of CD36, the scavenger receptor, and calpain-1, the Ca2+
      sensitive cysteine protease, in oxidized low-density lipoprotein (oxLDL)-treated
      macrophages. In this in vivo study, we investigated whether simvastatin
      downregulates the expression of CD36 and calpain-1 and inhibits the inflammation
      and atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. METHODS: Twenty
      male 6-week-old ApoE KO mice were divided into 2 groups: the ApoE KO group and
      the ApoE KO + simvastatin (ApoE KO + Sim) group. Atherosclerotic lesions were
      evaluated and the expressions of CD68, CD36, and calpain-1 in aorta were
      examined. RESULTS: Simvastatin inhibited the atherosclerotic lesion in ApoE KO
      mice. In addition, simvastatin reduced the contents of oxLDL, thiobarbituric acid
      reactive substances, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha) in serum, decreased the mRNA and protein expressions of CD36 and reduced
      the mRNA expression of TNF-alpha and IL-6 in the aortas. Furthermore, simvastatin
      reduced the calpain activity and the protein expression of calpain-1 in the
      aorta. CONCLUSION: The results suggested that the attenuation of atherosclerotic
      lesions in ApoE KO mice by simvastatin might be associated with the
      downregulations of CD36 and calpain-1 and with inflammation.

PMID- 28448975
TI  - Validation of a Case-Finding Algorithm for Hidradenitis Suppurativa Using
      Administrative Coding from a Clinical Database.
AB  - BACKGROUND: Requisite to the application of clinical databases for observational
      research in hidradenitis suppurativa (HS) is the identification of an accurate
      case cohort. OBJECTIVE: To assess the validity of utilizing administrative codes
      to establish the HS cohort from a large clinical database. METHODS: In this
      retrospective study using chart review as the reference standard, we calculated
      several estimates of the diagnostic accuracy of at least 1 ICD-9 code for HS.
      RESULTS: Estimates of the diagnostic accuracy of at least 1 ICD-9 code for HS
      include sensitivity 100% (95% CI 98-100), specificity 83% (95% CI 77-88),
      positive predictive value 79% (95% CI 72-85), negative predictive value 100% (95%
      CI 98-100), accuracy 90% (95% CI 86-93), and kappa statistic 79% (95% CI 73-86).
      CONCLUSION: The case-finding algorithm employing at least 1 ICD-9 code for HS
      provides balance in achieving accuracy and adequate power, both necessary in the
      evaluation of a less common disease and its potential association with uncommon
      or even rare events.

PMID- 28448974
TI  - The Feasibility and Safety of Interventional Occlusion Treatment of Intracristal
      Ventricular Septal Defects: Clinical Report of 56 Cases.
AB  - BACKGROUND: To investigate the feasibility and safety of the O eccentric shape
      occluder in the interventional occlusion treatment of intracristal ventricular
      septal defect (IVSD). METHODS: A retrospective analysis of the clinical data of
      56 IVSD patients treated by interventional occlusion at our center, as well as
      recording of their intraoperative and postoperative status, was performed.
      RESULTS: Of the 56 patients, a total of 48 patients underwent successful
      occlusion during the first surgical attempt. Four patients were transferred to
      the Surgery Department after occlusion when the largest occluder failed because
      of large defects. Two patients exhibited aortic valve regurgitation; 1 patient
      had mild regurgitation, which was not worsened after 6 months of follow-up. One
      patient had severe aortic regurgitation, and 2 days after the operation, the
      patient underwent a second operation. One patient exhibited a residual shunt,
      which was above the occluder; after 1 year of follow-up, re-occlusion was
      successful and eliminated the shunt. One patient developed complete right bundle
      branch block. CONCLUSION: Most IVSD interventional occlusion treatments are
      feasible and safe.

PMID- 28448977
TI  - Is Human Oxoguanine Glycosylase 1 Genetic Variant Successful Even on Oral
      Squamous Cell Carcinoma?
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most widespread
      cancer types that arise from different sites of oral cavity and has a 5-year
      survival rate. This study is aimed at investigating the human oxoguanine
      glycosylase 1 (hOGG1)-Ser326Cys and APE-Asp148Glu polymorphisms of DNA repair
      genes in OSCC. MATERIALS AND METHODS: We investigated the hOGG1-Ser326Cys and APE
      Asp148Glu polymorphisms of DNA repair genes in the oral cavity. Genotyping was
      conducted using polymerase chain reaction-restriction fragment length
      polymorphism analysis based on 132 patients who were diagnosed as having OSCC and
      160 healthy subjects. RESULTS: Individuals with the genotype hOGG1-Ser326Cys, Cys
      allele carriers, were found significantly more frequently in the patient group
      compared to the control group as increase in risk (p < 0.001). Furthermore, it
      was observed that there were significantly more individuals with the Ser allele
      in the control group (p < 0.001). Individuals with genotype APE-Asp148Glu were
      not statistically significant; however, they were still more in the control group
      and provided protection against the disease. CONCLUSION: Our findings showed that
      hOGG1-Ser326Cys Cys allele is statistically important and relevant with respect
      to the development of oral squamous cancer. In view of our results, further
      studies including expression levels are required in which hOGG1-Ser326Cys should
      be investigated as molecular biomarkers for the early prediction of squamous cell
      carcinoma.

PMID- 28448978
TI  - Quantitative Evaluation of Brain Stem Atrophy Using Magnetic Resonance Imaging in
      Adult Patients with Alexander Disease.
AB  - Brain MRI in adult patients with Alexander disease (AxD) mainly shows atrophy in
      the medulla oblongata. However, currently there is no quantitative standard for
      assessing this atrophy. In this study, we quantitatively evaluated the brain stem
      of AxD patients with glial fibrillary acidic protein (GFAP) mutation using
      conventional MRI to evaluate its usefulness as an aid to diagnosing AxD in daily
      clinical practice. Nineteen AxD patients with GFAP mutation were compared with 14
      patients negative for GFAP mutation in whom AxD was suspected due to "atrophy of
      the medulla oblongata." In the GFAP mutation-positive group, the sagittal
      diameter of the medulla oblongata, the ratio of the diameter of the medulla
      oblongata to that of the midbrain (MO/MB), and the ratio of the sagittal diameter
      of the medulla oblongata to that of the pons (MO/Po) were significantly smaller
      compared to those of the GFAP mutation-negative group (p < 0.01). The sensitivity
      and specificity of each parameter were 87.5 and 92.3%, 91.7 and 81.3%, and 88.2
      and 100% with a sagittal diameter of the medulla oblongata <9.0 mm, MO/MB <0.60,
      and sagittal MO/Po <0.46, respectively. These parameters can provide very useful
      information to differentially diagnose AxD from other disorders associated with
      brain stem atrophy in adult patients.

PMID- 28448980
TI  - [The Concept of 'Integrative and Personalized Health Care'].

PMID- 28448979
TI  - Combination of Correctors Rescues CFTR Transmembrane-Domain Mutants by Mitigating
      their Interactions with Proteostasis.
AB  - BACKGROUND/AIMS: Premature degradation of mutated cystic fibrosis transmembrane
      conductance regulator (CFTR) protein causes cystic fibrosis (CF), the commonest
      Mendelian disease in Caucasians. Despite recent advances in precision medicines
      for CF patients, many CFTR mutants have not been characterized and the effects of
      these new therapeutic approaches are still unclear for those mutants. METHODS:
      Cells transfected or stably expressing four CFTR transmembrane-domain mutants
      (G85E, E92K, L1077P, and M1101K) were used to: 1) characterize the mutants
      according to their protein expression, thermal sensitivity, and degradation
      pathways; 2) evaluate the effects of correctors in rescuing them; and 3) explore
      the effects of correctors on CFTR interactions with proteostasis components.
      RESULTS: All four mutants exhibited lower protein expression than did wild type
      CFTR, and they were degraded by proteasomes and aggresomes. At low temperature,
      only cells expressing the mutants L1077P and M1101K exhibited increased CFTR
      maturation. Co-administration of C4 and C18 showed the greatest effect, restoring
      functional expression and partial stability of CFTR bearing E92K, L1077P, or
      M1101K at the cell surface. However, this treatment was inefficient in rectifying
      the defect of CFTR bearing G85E. Correctors rescued CFTR mutants by reducing
      their interactions with proteostasis components associated with protein retention
      in the endoplasmic reticulum and ubiquitination. CONCLUSION: Co-administration of
      C4 and C18 rescued CFTR transmembrane-domain mutants by remodeling the CFTR
      interactome.

PMID- 28448981
TI  - Safety and Efficacy of a Fully Covered Self-Expandable Metallic Stent in Benign
      Airway Stenosis.
AB  - BACKGROUND: The use of self-expandable metallic stents (SEMS) in benign airway
      disease was the object of a boxed warning from the United States Food and Drug
      Administration in 2005 due to the risk of stent-related complications and
      difficulties associated with their removal. Third-generation fully covered SEMS
      have been commercialized since this warning and theoretically should not present
      the same difficulties associated with removal as they cannot become embedded in
      the airway mucosa. OBJECTIVES: We aimed to examine the safety and efficacy of a
      specific third-generation SEMS, the Silmet stent. METHODS: We reviewed the
      records of all patients treated for benign airway stenosis with third-generation
      Silmet SEMS from January 2011 to December 2015 at the North Hospital of
      Marseilles, France. RESULTS: Forty SEMS were inserted in 30 patients over this
      period. Twenty (50.0%) stents were removed because of stent-related complications
      after a median of 77.0 +/- 96.6 days (migration 32.5%, granulation tissue
      formation 7.5%, subjective intolerance 5.0%, mucus plugging 2.5%, laryngeal edema
      2.5%). There were no cases of stent-related mortality. All complications were
      managed successfully endoscopically. Thirty-six stents (90.0%) were removed
      successfully after a median of 122.0 +/- 113.2 days without any complications.
      The clinical success rate of stent treatment was 40.7%. CONCLUSION: Third
      generation SEMS are a safe treatment option for complex benign airway stenosis,
      but complications requiring stent removal are frequent. Further studies are
      needed to compare the performance of third-generation SEMS and silicone stents in
      benign airway stenosis.

PMID- 28448982
TI  - PharmaNews.

PMID- 28448984
TI  - Meetings and Conferences.

PMID- 28448983
TI  - Intrauterine Growth Restriction Alters the Postnatal Development of the Rat
      Cerebellum.
AB  - Intrauterine growth restriction (IUGR) is a major cause of antenatal brain
      injury. We aimed to characterize cerebellar deficits following IUGR and to
      investigate the potential underlying cellular and molecular mechanisms. At
      embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23)
      or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n =
      20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights
      were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with
      controls. At P7, the width of the external granule layer (EGL) was 30% greater in
      IUGR than control rats (p < 0.05); there was no difference in the width of the
      proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann
      glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10%
      decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At
      P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were
      decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were
      increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no
      difference in ASTN1 protein. The expressions of other factors known to regulate
      cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2
      receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were
      not different between IUGR and control rats at P7 or P35. These data suggest that
      damage to the migratory scaffold (Bergmann glial fibers) and alterations in the
      genes that influence migration (Trop2 and Astn1) may underlie the deficits in
      postnatal cerebellar development following IUGR.

PMID- 28448985
TI  - Total Skin Electron Beam Therapy as Part of Multimodal Treatment Strategies for
      Primary Cutaneous T-Cell Lymphoma.
AB  - Total-skin electron beam therapy (TSEBT) is one of most effective treatments that
      has been used for cutaneous T-cell lymphoma. Low-dose TSEBT regimens (10-12 Gy)
      appear to be an effective alternative to conventional-dose TSEBT (30-36 Gy),
      yielding short-term remission of cutaneous manifestations with minimal toxicity.
      TSEBT can be administered to patients any time after a diagnosis of mycosis
      fungoides (MF). Patients requiring rapid relief from cutaneous lesions or
      symptoms may particularly benefit from TSEBT as an initial therapy. Radiotherapy
      (RT) dose, boost radiation delivery, maintenance treatment, and radiation
      tolerability may enhance remission rates and improve relapse-free survival
      following TSEBT. In addition, salvage local RT or TSEBT may be safely applied
      with high effectiveness. In this review, we focus on the use of TSEBT in patients
      with several forms of primary cutaneous T-cell lymphoma, and highlight the
      potential of low-dose TSEBT as part of a promising therapeutic approach.

PMID- 28448986
TI  - PharmaForum.

PMID- 28448987
TI  - A Role for Oxytocin-Like Receptor in Social Habituation in a Teleost.
AB  - Oxytocin (OT) mediates social habituation in rodent model systems, but its role
      in mediating this effect in other vertebrates is unknown. We used males of the
      African cichlid fish, Astatotilapia burtoni, to investigate two aspects of
      isotocin (IT; an OT homolog) signaling in social habituation. First, we examined
      the expression of IT receptor 2 (ITR2) as well as two immediate early genes in
      brain regions implicated in social recognition. Next, we examined IT neuron
      activity using immunohistochemistry. Patterns of gene expression in homologs of
      the amygdala and hippocampus implicate IT signaling in these regions in social
      habituation to a territorial neighbor. In the preoptic area, the expression of
      the ITR2 subtype and IT neuron activity respond to the presence of a male,
      independent of familiarity. Our results implicate IT in mediating social
      habituation in a teleost.

PMID- 28448989
TI  - PharmaNews.

PMID- 28448990
TI  - PharmaNews.

PMID- 28448988
TI  - Anaemia following Artemisinin-Based Combination Treatments of Uncomplicated
      Plasmodium falciparum Malaria in Children: Temporal Patterns of Haematocrit and
      the Use of Uncomplicated Hyperparasitaemia as a Model for Evaluating Late
      Appearing Anaemia.
AB  - BACKGROUND: In severe malaria, intravenous artesunate may cause delayed
      haemolytic anaemia but there has been little evaluation of the propensity of oral
      artemisinin-based combination treatments (ACTs) to cause late-appearing anaemia.
      METHODS: The frequency of anaemia (haematocrit <30%), and temporal changes in
      haematocrit were evaluated in 1,191 malarious children following ACTs.
      "Haematocrit conservation" was evaluated by using the fall in haematocrit/1,000
      asexual parasites cleared from the peripheral blood (FIH/1,000 asexual parasites
      cpb), and the ratio of the average haematocrit (on the first 3 days of starting
      treatment):total parasitaemia cleared. RESULTS: The frequency of anaemia
      decreased significantly following treatment. FIH/1,000 asexual parasites cpb,
      average haematocrit:total parasitaemia cleared, and mean haematocrit 5 weeks
      after treatment began were significantly lower in hyperparasitaemic children than
      in children without hyperparasitaemia, suggesting haematocrit conservation during
      treatment followed later by a loss of haematocrit. Asymptomatic late-appearing
      anaemia occurred in 6% of the children. CONCLUSION: Artesunate-amodiaquine and
      artemether-lumefantrine contribute to haematocrit conservation at high
      parasitaemias but may cause late-appearing anaemia.

PMID- 28448991
TI  - Participation of Antidiuretic Hormone (ADH) in Asthma Exacerbations Induced by
      Psychological Stress via PKA/PKC Signal Pathway in Airway-Related Vagal
      Preganglionic Neurons (AVPNs).
AB  - AIMS: Present study was performed to examine whether ADH was implicated in
      psychological stress asthma and to explore the underlying molecular mechanism.
      METHODS: We not only examined ADH levels in the cerebrospinal fluid (CSF) via
      radioimmunoassay, but also measured ADH receptor (ADHR) expression in airway
      related vagal preganglionic neurons (AVPNs) through real-time PCR in all
      experimental mice. Western blotting was performed to evaluate the relationship
      between ADH and PKA/PKC in psychological stress asthma. Finally, the role of
      PKA/PKC in psychological stress asthma was analyzed. RESULTS: Marked asthma
      exacerbations were noted owing to significantly elevated levels of ADH and ADHR
      after psychological stress induction as compared to OVA alone (asthma group).
      ADHR antagonists (SR-49095 or SR-121463A) dramatically lowered higher protein
      levels of PKAalpha and PKCalpha induced by psychological stress as compared to
      OVA alone, suggesting the correlation between ADH and PKA/PKC in psychological
      stress asthma. KT-5720 (PKA inhibitor) and Go-7874 (PKC inhibitor) further
      directly revealed the involvement of PKA/PKC in psychological stress asthma. Some
      notable changes were also noted after employing PKA and PKC inhibitors in
      psychological stress asthma, including reduced asthmatic inflammation (lower
      eosinophil peroxidase (EPO) activity, myeloperoxidase (MPO) activity,
      immunoglobulin E (IgE) level, and histamine release), substantial decrements in
      inflammatory cell counts (eosinophils and lymphocytes), and decreased cytokine
      secretion (IL-6, IL-10, and IFN-gamma), indicating the involvement of PKA/PKC in
      asthma exacerbations induced by psychological stress. CONCLUSION: Our results
      strongly suggested that ADH participated in psychological stress-induced asthma
      exacerbations via PKA/PKC signal pathway in AVPNs.

PMID- 28448992
TI  - Bethesda Made It Clearer: A Review of 542 Patients in a Single Institution.
AB  - BACKGROUND: It is essential to interpret fine needle aspiration biopsy (FNAB)
      material correctly to create a common language among pathologists and surgeons,
      leading to a uniform approach to thyroid nodule management. We aimed to compare
      FNAB reports of patients at our institution who were treated with total
      thyroidectomy, before and after the Bethesda classification system. PATIENTS AND
      METHODS: Patients who underwent total thyroidectomy for thyroid nodules are
      reviewed. 226 patients who underwent total thyroidectomy before the Bethesda era
      (2006-2009) were classified as Group-I, and 316 patients in whom total
      thyroidectomy was performed after the Bethesda classification system was
      introduced (2010-2014) were classified as Group-II. RESULTS: Before Bethesda,
      'nondiagnostic' or 'benign' lesions were reported in 16.4 and 45% of patients,
      respectively, which then significantly decreased to 4.7 and 32.9% as the Bethesda
      classification criteria came into use. In Group-II, the actual malignancy rates
      were 13.3, 2.8, 7.3, 15.5, 85.4, and 96.5% for Bethesda I, II, III, IV, V, and
      VI, respectively. CONCLUSION: Our experience confirms that the Bethesda
      classification system leads to a significant reduction in lesions that used to be
      reported as 'benign' without compromising the actual rates of malignancy. It
      ensures better classification of so-called suspicious lesions, and allows for
      more accurate predictions of suspicious or malignant lesions.

PMID- 28448993
TI  - The Long Non-Coding RNA XIST Controls Non-Small Cell Lung Cancer Proliferation
      and Invasion by Modulating miR-186-5p.
AB  - BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) are key players in the
      development and progression of human cancers. The lncRNA XIST (X-inactive
      specific transcript) has been shown to be upregulated in human non-small cell
      lung cancer (NSCLC); however, its role and molecular mechanisms in NSCLC cell
      progression remain unclear. METHODS: qRT-PCR was conducted to assess the
      expression of XIST and miR-186. Cell proliferation was detected using MTT assay.
      Cell invasion and migration were evaluated using transwell assay. Cell cycle
      distribution and apoptosis rates were analyzed by flow cytometry. Luciferase
      reporter assay was used to identify the direct regulation of XIST and miR-186. A
      RNA immunoprecipitation was used to analyze whether XIST was associated with the
      RNA-induced silencing complex (RISC). RESULTS: We confirmed that XIST was
      upregulated in NSCLC cell lines and tissues. Functionally, XIST knockdown
      inhibited cancer cell proliferation and invasion, and induced apoptosis in vitro,
      and suppressed subcutaneous tumor growth in vivo. Mechanistic investigations
      revealed a reciprocal repressive interaction between XIST and miR-186-5p.
      Furthermore, we showed that miR-186-5p has a binding site for XIST. Our data also
      indicated that XIST and miR-186-5p are likely in the same RNA induced silencing
      complex. CONCLUSION: Together, our data revealed that XIST knockdown confers
      suppressive function in NSCLC and XIST may be a novel therapeutic marker in this
      disease.

PMID- 28448996
TI  - PharmaNews.

PMID- 28448995
TI  - Cytoprotective Effect of Heat Shock Protein 27 Against Lipopolysaccharide-Induced
      Apoptosis of Renal Epithelial HK-2 Cells.
AB  - BACKGROUND: In response to various stimuli, heat shock protein 27 (Hsp27)
      functions as an anti-apoptotic or/and anti-inflammatory factor which confers a
      survival advantage to cells. This study was aimed to explore whether Hsp27 also
      has a cytoprotective role in human renal tubular epithelial cells, and to
      evaluate its potential in treating septic acute kidney injury (septic AKI).
      METHODS: HK-2 cells were subjected to different concentrations (0-10 ug/mL) of
      lipopolysaccharide (LPS) for various times (0-24 h) to establish a septic AKI
      model in vitro. Before LPS administration, HK-2 cells were transfected either
      with vectors or siRNA against Hsp27, and the changes in cell viability and
      apoptotic cells rate were assessed using CCK-8 and flow cytometry. The expression
      changes in apoptosis-related proteins, proinflammatory cytokines and chemokine,
      as well as main factors in NF-kappaB and JNK pathways were mainly determined by
      Western blotting. Besides, the relationship between Hsp27 and Bcl-2 was detected
      by co-immunoprecipitation. RESULTS: LPS remarkably damaged HK-2 cells by
      reduction of cell viability, induction of apoptosis, and stimulation of
      proinflammatory cytokines and chemokine release. Hsp27 overexpression
      significantly impaired LPS-induced damage in HK-2 cells. Hsp27 overexpression
      couldn't alter the mRNA level of Bcl-2, but could interact with Bcl-2 at an
      endogenous level. Both NF-kappaB and JNK pathways were activated by LPS, while
      were blocked in Hsp27-overexpressing cells. CONCLUSION: Hsp27 overexpression
      conferred a survival advantage to LPS-injured HK-2 cells by controlling cell
      viability, apoptosis and inflammation, possibly via interaction with Bcl-2 and
      modulation of NF-kappaB and JNK pathways.

PMID- 28448997
TI  - Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic
      Cholangiocarcinoma.
AB  - OBJECTIVE: MOB1, a core component of the Hippo signaling pathway, suppresses cell
      proliferation, and MOB1 liver conditional knockout mice develop intrahepatic
      cholangiocarcinoma (ICC). However, its clinical significance in human ICC has not
      been established. The aim of this study was to characterize protein levels and
      the role of Hippo and TGF pathways in ICCs. METHODS: The protein levels of yes
      associated protein 1 (YAP1), MOB1, Smad2, and TGFbeta2 in 88 ICC cases were
      analyzed. Protein level was graded by a scoring system; then, the
      clinicopathological factors, including prognosis, were analyzed based on protein
      level. RESULTS: Nuclear overexpression of YAP1 was seen in 28 cases (31.8%), and
      it was significantly associated with a poor overall survival rate (p = 0.01).
      MOB1 expression decreased in 42 cases (47.7%) and was associated with a poor
      overall survival rate (p = 0.02). SMAD2 nuclear localization was significantly
      correlated with a high YAP1 level independent of TGFbeta2. Multivariate analysis
      revealed that a high YAP1 level, a low MOB1 level, and lymphatic permeation were
      independent risk factors for overall survival. CONCLUSIONS: These results showed
      that key components of the Hippo signaling pathway are aberrantly expressed and
      associated with the malignant potential of human ICC.

PMID- 28448999
TI  - Outcome of All-Oral Direct-Acting Antiviral Regimens on the Rate of Development
      of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Genotype 1-Related
      Chronic Liver Disease.
AB  - OBJECTIVES: There is little information on the risk factors for hepatocellular
      carcinoma (HCC) and outcome of treatment with an all-oral combination of direct
      acting antiviral regimens following eradication of hepatitis C virus (HCV) RNA.
      METHODS: The study subjects were 1,170 patients with HCV genotype 1-related
      chronic liver disease treated with either NS5A inhibitor plus NS3/4A protease
      inhibitor (n = 707), NS5A inhibitor plus NS5B polymerase inhibitor (n = 345), or
      NS5A inhibitor, NS3/4A protease inhibitor plus ritonavir (n = 118), for 12-24
      weeks. All patients were free of HCC before and during therapy. RESULTS: In this
      retrospective study, 22 patients developed HCC during the follow-up (time from
      the end of antiviral therapy until the last visit: 1.3 years). At 1 and 2 years
      after completion of the treatment, the cumulative HCC rates for the whole group
      were 1.8 and 2.3%, respectively, and 1.4 and 1.8%, respectively, for 1,065
      patients who showed sustained virological response (SVR). The risk factors for
      HCC identified by multivariate analysis were hypoalbuminemia, thrombocytopenia, a
      high alpha-fetoprotein level, and non-SVR for all patients, and hypoalbuminemia
      and a high alpha-fetoprotein level for patients with SVR. CONCLUSION: Eradication
      of HCV RNA by direct-acting antiviral regimens might reduce the risk of HCC.
      Albumin and alpha-fetoprotein levels are significant risk factors for HCC.

PMID- 28448998
TI  - Efficacy, Safety, and Tolerability of Armodafinil Therapy for Hypersomnia
      Associated with Dementia with Lewy Bodies: A Pilot Study.
AB  - BACKGROUND/AIMS: Hypersomnia is common in dementia with Lewy bodies (DLB). We
      assessed the efficacy, safety, and tolerability of armodafinil for hypersomnia
      associated with DLB. METHODS: We performed a 12-week pilot trial of armodafinil
      therapy (125-250 mg orally daily) in DLB outpatients with hypersomnia. The
      patients underwent neurologic examinations, a neuropsychological battery,
      laboratory testing, electrocardiography, and polysomnography. Efficacy was
      assessed at 2, 4, 8, and 12 weeks. Safety assessment included laboratory
      examinations, QTc interval, and heart rate. Tolerability was assessed by analysis
      of adverse events. Data were analyzed using the last-observation-carried-forward
      method. RESULTS: Of 20 participants, 17 completed the protocol. The median age
      was 72 years, most of the participants were men (80%), and most had spouses as
      caregivers. The Epworth Sleepiness Scale (p < 0.001), Maintenance of Wakefulness
      Test (p = 0.003), and Clinical Global Impression of Change (p < 0.001) scores
      improved at week 12. The Neuropsychiatric Inventory total score (p = 0.003),
      visual hallucinations (p = 0.003), and agitation (p = 0.02) improved at week 4.
      Caregiver overall quality of life improved at week 12 (p = 0.004). No adverse
      events occurred. CONCLUSION: These pilot data suggest improvements in hypersomnia
      and wakefulness and reasonable safety and tolerability of armodafinil therapy in
      hypersomnolent patients with DLB. Our findings inform the use of pharmacologic
      strategies for managing hypersomnolence in these patients.

PMID- 28449000
TI  - Three-Year Follow-Up of Trabeculectomy with 5-Fluorouracil.
AB  - PURPOSE: To evaluate the long-term outcome of trabeculectomy with intra- and
      postoperative 5-fluorouracil (5-FU) application in glaucoma. METHODS: Eighty-six
      patients with glaucoma planned for primary trabeculectomy with 5-FU and a minimum
      follow-up of 3 years were retrospectively analyzed. Success rates, postsurgical 5
      FU injections, needling procedures, and complications were analyzed. RESULTS:
      Mean intraocular pressure (IOP) decreased from 27.2 +/- 6.7 to 13.2 +/- 4.2 mm Hg
      at 1 year and 13.8 +/- 3.7 mm Hg at the 3-year follow-up. The complete success
      rates (no IOP-lowering medication) were 83, 79, 73, and 45% at 1 year for IOP
      <=21, <=18, <=16, and <=12 mm Hg, respectively, and 64, 59, 56, and 20% for these
      criteria at 3 years. The average number of medications decreased from
      preoperatively 2.9 +/- 1.4 to 0.2 +/- 0.5 at 1 year and 0.7 +/- 1.1 at 3 years.
      During the first 6 months, subconjunctival 5-FU injections were performed in 49
      cases. Eleven patients underwent bleb needling during the first 6 months and 13
      patients underwent the procedure between the 6th month and the 3rd year.
      Malignant glaucoma and bleb-related endophthalmitis occurred in 1 patient each.
      CONCLUSIONS: Trabeculectomy with 5-FU is an efficient surgical procedure for
      glaucoma treatment when combined with intensified postsurgical care.

PMID- 28449002
TI  - Purification and Biochemical and Kinetic Properties of an Endo-Polygalacturonase
      from the Industrial Fungus Aspergillus sojae.
AB  - An endo-polygalacturonase secreted by Aspergillus sojae was characterized after
      being purified to homogeneity from submerged cultures with orange peel as the
      sole carbon source by gel filtration and ion-exchange chromatographies. According
      to SDS-PAGE and analytical isoelectric focusing analyses, the enzyme presents a
      molecular weight of 47 kDa and pI value of 4.2. This enzyme exhibits considerable
      stability under highly acidic to neutral conditions (pH 1.5-6.5) and presents a
      half-life of 2 h at 50 degrees C. Besides its activity towards pectin and
      polygalacturonic acid, the enzyme displays pectin-releasing activity, acting best
      in a pH range of 3.3-5.0. Thin-layer chromatographic analysis revealed that tri
      galacturonate is the main enzymatic end product of polygalacturonic acid
      hydrolysis, indicating that it is an endo-polygalacturonase. The enzyme exhibits
      Michaelis-Menten kinetics, with KM and VMAX values of 0.134 mg/mL and 9.6
      umol/mg/min, respectively, and remained stable and active in the presence of SO2,
      ethanol, and various cations assayed except Hg2+.

PMID- 28449003
TI  - Pneumonia Severity Assessment Tools for Predicting Mortality in Patients with
      Healthcare-Associated Pneumonia: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: In contrast to community-acquired pneumonia (CAP), no specific
      severity assessment tools have been developed for healthcare-associated pneumonia
      (HCAP) in clinical practice. OBJECTIVES: In this review, we assessed the clinical
      significance of severity assessment tools for HCAP. METHODS: We identified
      related articles from the PubMed database. The eligibility criteria were original
      research articles evaluating severity scoring tools and reporting the outcomes of
      mortality in patients with HCAP. RESULTS: Eight articles were included in the
      meta-analysis. The PORT score and CURB-65 were evaluated in 7 and 8 studies,
      respectively. Using cutoff values of >=IV and V for the PORT score, the
      diagnostic odds ratios (DORs) were 5.28 (2.49-11.17) and 3.76 (2.88-4.92),
      respectively, and the areas under the curve (AUCs) were 0.68 (0.64-0.72) and 0.71
      (0.67-0.75), respectively. Conversely, the AUCs for >=IV and V were 0.71 (0.67
      0.76) and 0.74 (0.70-0.78), respectively, when applied only to
      nonimmunocompromised patients. In contrast, when using cutoff values of >=2 and
      >=3 for CURB-65, the DORs were 3.35 (2.26-4.97) and 2.65 (2.05-3.43),
      respectively, and the AUCs were 0.65 (0.61-0.69) and 0.66 (0.62-0.70),
      respectively. Conversely, the AUCs for >=2 and >=3 were 0.65 (0.61-0.69) and 0.68
      (0.64-0.72), respectively, when applied only to nonimmunocompromised patients.
      CONCLUSIONS: The PORT score and CURB-65 do not have substantial power compared
      with the tools for CAP patients, although the PORT score is more useful than CURB
      65 for predicting mortality in HCAP patients. According to our results, however,
      these tools, especially the PORT score, can be more useful when limited to
      nonimmunocompromised patients.

PMID- 28449004
TI  - Minimal Detectable Change for Balance Measurements in Patients With COPD.
AB  - PURPOSE: The purpose of this study was to determine the reliability and minimal
      detectable change (MDC) of various outcome measures that are potentially suitable
      for evaluating postural control in individuals with chronic obstructive pulmonary
      disease (COPD). METHODS: This was a test-retest reliability study. Participants
      with COPD were asked to complete 5 balance assessments, separated by 1 week. The
      assessments included Timed Up and Go (TUG) Test, Unipodal Stance Test (UST),
      Tinetti Test, Berg Balance Scale (BBS), and the Activities Balance Confidence
      (ABC) scale. Test-retest reliability using intraclass correlation coefficients
      and MDC values were calculated for each assessment. RESULTS: All 5 outcome
      measures were found to have excellent test-retest reliability (r > 0.90). The
      MDC95 values were 3.01 seconds and 4.03 seconds for the TUG Test and the UST,
      respectively; 3.23 points and 3.46 points for the Tinetti Test and the BBS,
      respectively; and 8.25% for the ABC scale. CONCLUSION: The TUG, UST, BBS, the
      Tinetti Test, and the ABC scale are reliable outcome measures for use with people
      with COPD, recognizing that individual variability of performance is high.
      Minimal detectable change scores at the 95% CI can be used to assess change in
      performance over time and the impact of interventions in this population.

PMID- 28449005
TI  - Concussion in Ice Hockey-A Cohort Study Across 29 Seasons.
AB  - OBJECTIVE: The aim of this study was to analyze the concussion incidence rate
      ratios across 29 seasons in a Swedish Hockey League team. DESIGN: Cohort study
      over 29 seasons within one Swedish elite series ice hockey team. PARTICIPANTS:
      All players who were part of one Swedish elite ice hockey team during the
      research period gave consent for participation in the study. INDEPENDENT
      VARIABLES: Exposure to top-level Swedish ice hockey. MAIN OUTCOME MEASURES:
      Incidence rate ratio for concussion and rehabilitation periods due to concussion
      were calculated and analyzed. RESULTS: During the research period, 267 players in
      total were part of the team. A total of 1638 traumatic injuries were registered,
      of which 162 were concussions. Incidence rates (IRs) ranged from 0/1000 games
      during the first season to 118/1000 games for the final recorded season. The
      incidence rate ratio was 1.06 (confidence interval, 1.03-1.10) for the entire
      research period. A shift toward longer rehabilitation periods was discovered.
      CONCLUSIONS: This study showed a significant increase of concussion IR and a
      trend toward longer rehabilitation periods due to concussion. Possible risk
      factors were discussed. Risk behavior and rehabilitation protocols should be
      prioritized areas in the research of concussion in ice hockey.

PMID- 28449006
TI  - A meta-analysis comparing the risk of metastases in patients with rectal cancer
      and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases.
AB  - BACKGROUND: Pathological extramural vascular invasion (EMVI) is an independent
      prognostic factor in rectal cancer, but can also be identified on MRI-detected
      extramural vascular invasion (mrEMVI). We perform a meta-analysis to determine
      the risk of metastatic disease at presentation and after surgery in mrEMVI
      positive patients compared with negative tumours. METHODS: Electronic databases
      were searched from January 1980 to March 2016. Conventional meta-analytical
      techniques were used to provide a summative outcome. Quality assessment of the
      studies was performed. RESULTS: Six articles reported on mrEMVI in 1262 patients.
      There were 403 patients in the mrEMVI-positive group and 859 patients in the
      mrEMVI-negative group. The combined prevalence of mrEMVI-positive tumours was
      0.346(range=0.198-0.574). Patients with mrEMVI-positive tumours presented more
      frequently with metastases compared to mrEMVI-negative tumours (fixed effects
      model: odds ratio (OR)=5.68, 95% confidence interval (CI) (3.75, 8.61), z=8.21,
      df=2, P<0.001). Patients who were mrEMVI-positive developed metastases more
      frequently during follow-up (random effects model: OR=3.91, 95% CI (2.61, 5.86),
      z=6.63, df=5, P<0.001). CONCLUSIONS: MRI-detected extramural vascular invasion is
      prevalent in one-third of patients with rectal cancer. MRI-detected extramural
      vascular invasion is a poor prognostic factor as evidenced by the five-fold
      increased rate of synchronous metastases, and almost four-fold ongoing risk of
      developing metastases in follow-up after surgery.

PMID- 28449007
TI  - Efficacy of stereotactic body radiotherapy in oligorecurrent and in
      oligoprogressive prostate cancer: new evidence from a multicentric study.
AB  - BACKGROUND: The aim of the present study is to evaluate the impact of metastases
      directed stereotactic body radiotherapy in two groups of oligometastatic prostate
      cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant
      PC (oligo-CRPC). METHODS: Inclusion criteria of the present multicentre
      retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1
      3 lesions (bone or nodes) detected with choline positron emission tomography or
      CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as
      metastases (bone or nodes) detected after a prostatic-specific antigen rise
      during androgen deprivation therapy (ADT). Primary end points were: distant
      progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC
      patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC
      patients. RESULTS: About 100 patients with oligorecurrent PC (139 lesions) and 41
      with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were
      analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1-
      and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a
      median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were
      43.2 and 21.6%. Limitations include the retrospective design. CONCLUSIONS:
      Stereotactic body radiotherapy seems to be a useful treatment both for
      oligorecurrent and oligo-CRPC.

PMID- 28449008
TI  - Extended RAS analysis and correlation with overall survival in advanced
      pancreatic cancer.
AB  - BACKGROUND: Mutations in the KRAS gene can be detected in about 70-90% of
      pancreatic cancer (PC) cases. Whether these mutations have a prognostic or
      predictive value remains elusive. Furthermore, the clinical relevance of the
      extended RAS (KRAS+NRAS) mutational status is unclear in PC. METHODS: We
      prospectively defined a PC patient population who received erlotinib-free
      chemotherapy regimens. A statistically significant difference between KRAS wild
      type and KRAS mutated tumours in at least 160 patients in this population would
      support the assumption of a rather prognostic role of KRAS. RESULTS: One hundred
      and seventy-eight tumour samples were collected from prospective clinical studies
      and successfully analysed for the extended RAS status: 37 tumours were KRAS wild
      type (21%), whereas 141 (79%) carried a KRAS mutation; 132 of these mutations
      were found in KRAS exon 2 (74%), whereas only 9 mutations (5%) were detected in
      KRAS exon 3. Within KRAS exon 4 and NRAS exons 2-4, no mutations were apparent.
      There was no significant difference in overall survival for KRAS wild-type vs
      mutant patients (9.9 vs 8.3 months, P=0.70). CONCLUSIONS: Together with the
      results of the AIO-PK-0104-trial, the present analysis supports the notion that
      KRAS mutation status is rather predictive than prognostic in advanced PC.

PMID- 28449009
TI  - The prognostic value of dynamic contrast-enhanced MRI contrast agent transfer
      constant Ktrans in cervical cancer is explained by plasma flow rather than vessel
      permeability.
AB  - BACKGROUND: The microvascular contrast agent transfer constant Ktrans has shown
      prognostic value in cervical cancer patients treated with chemoradiotherapy. This
      study aims to determine whether this is explained by the contribution to Ktrans
      of plasma flow (Fp), vessel permeability surface-area product (PS), or a
      combination of both. METHODS: Pre-treatment dynamic contrast-enhanced MRI (DCE
      MRI) data from 36 patients were analysed using the two-compartment exchange
      model. Estimates of Fp, PS, Ktrans, and fractional plasma and interstitial
      volumes (vp and ve) were made and used in univariate and multivariate survival
      analyses adjusting for clinicopathologic variables tumour stage, nodal status,
      histological subtype, patient age, tumour volume, and treatment type
      (chemoradiotherapy vs radiotherapy alone). RESULTS: In univariate analyses, Fp
      (HR=0.25, P=0.0095) and Ktrans (HR=0.20, P=0.032) were significantly associated
      with disease-free survival while PS, vp and ve were not. In multivariate analyses
      adjusting for clinicopathologic variables, Fp and Ktrans significantly increased
      the accuracy of survival predictions (P=0.0089). CONCLUSIONS: The prognostic
      value of Ktrans in cervical cancer patients treated with chemoradiotherapy is
      explained by microvascular plasma flow (Fp) rather than vessel permeability
      surface-area product (PS).

PMID- 28449011
TI  - Vitamins in humans: then, now and future global food and health.

PMID- 28449010
TI  - Excess of a Rassf1-targeting microRNA, miR-193a-3p, perturbs cell division
      fidelity.
AB  - BACKGROUND: Several microRNA (miRNA) molecules have emerged as important post
      transcriptional regulators of tumour suppressor and oncogene expression. Ras
      association domain family member 1 (RASSF1) is a critical tumour suppressor that
      controls multiple aspects of cell proliferation such as cell cycle, cell division
      and apoptosis. The expression of RASSF1 is lost in a variety of cancers due to
      the promoter hypermethylation. METHODS: miR-193a-3p was identified as a RASSF1
      targeting miRNA by a dual screening approach. In cultured human cancer cells,
      immunoblotting, qRT-PCR, luciferase reporter assays, time-lapse microscopy and
      immunofluorescence methods were used to study the effects of excess miR-193a-3p
      on RASSF1 expression and cell division. RESULTS: Here, we report a new miRNA
      mediated mechanism that regulates RASSF1 expression: miR-193a-3p binds directly
      to RASSF1-3'UTR and represses the mRNA and protein expression. In human cancer
      cells, excess of miR-193a-3p causes polyploidy through impairment of the Rassf1
      Syntaxin 16 signalling pathway that is needed for completion of cytokinesis. In
      the next cell cycle the miR-193a-3p-overexpressing cells exhibit multipolar
      mitotic spindles, mitotic delay and elevated frequency of cell death.
      CONCLUSIONS: Our results suggest that besides epigenetic regulation, altered
      expression of specific miRNAs may contribute to the loss of Rassf1 in cancer
      cells and cause cell division errors.

PMID- 28449012
TI  - Ethnic inequality in diagnosis with depression and anxiety disorders.
AB  - AIMS: This study explored ethnic disparities in self-reported diagnosis of
      depression or an anxiety disorder by a doctor, relative to scores on the
      screening measure for these same forms of mental illness in a probability sample
      of New Zealand adults. METHODS: 15,822 participants responded to the 2014/15 New
      Zealand Attitudes and Values Study (NZAVS) longitudinal panel. Participants
      completed the Kessler-6 scale (a screening measure of non-specific psychological
      distress over the last month) and reported whether a doctor had diagnosed them
      with depression or an anxiety disorder any time in the last five years. RESULTS:
      Maori, Pacific and Asian New Zealanders were more likely to score in the 'at
      risk' range of the Kessler-6 scale, indicating an increased likelihood of
      depression or anxiety, relative to European New Zealanders. However, European New
      Zealanders reported the highest rate of actual diagnosis with depression or
      anxiety in the previous five-year period. CONCLUSION: There is an ethnic
      inequality in diagnosis received in the last five years relative to population
      level screening risk for depression and anxiety disorders over the last month.
      Maori, Pacific and Asian New Zealanders are more likely to be under-diagnosed
      with depression and anxiety disorders relative to European New Zealanders. This
      inequality may reflect ethnic group differences in access to, expectations from
      and style of communication with, medical professionals.

PMID- 28449013
TI  - Suicide mortality among Pacific peoples in New Zealand, 1996-2013.
AB  - AIM: The aim of this study was to describe trends in suicide mortality for
      Pacific peoples in New Zealand by reviewing official data over the period 1996
      2013. METHOD: Death registrations where the underlying causes of death were
      intentional self-harm was examined and area of interest was identified and
      presented. RESULTS: Over a 17-year period (1996-2013), there were 380 total
      Pacific suicides (4.1%) out of 9,307 suicides nationally for New Zealand's total
      population. CONCLUSION: Priority areas for effective suicide prevention include:
      Pacific young males, Pacific ethnic foci, clear ethnic disparities and
      inequalities for Pacific suicide mortality when compared to New Zealand's total
      population; safe, ethical and culturally appropriate messaging around suicide
      methods; the importance of the role of mental health and addictions in suicide
      prevention. On average, there are at least 22 Pacific suicides annually in New
      Zealand. Irrespective of small numbers, further Pacific ethnic breakdown is
      needed other than Samoan, Cook Islands and Tongan, as this is problematic for
      suicide prevention efforts for the exclusion of other Pacific groups.

PMID- 28449015
TI  - 'Everyone's talking Jadelle': the experiences and attitudes of service providers
      regarding the use of the contraceptive implant, Jadelle in young people in New
      Zealand.
AB  - AIMS: The contraceptive implant Jadelle, along with other types of long-acting
      reversible contraception, is thought to be an ideal choice for young people
      wanting to avoid pregnancy, however, uptake is low. This study aimed to explore
      the attitudes and experiences of health professionals regarding the use of
      Jadelle in teenagers. METHODS: Semi-structured interviews were carried out with
      professionals providing contraceptive services to young people. Sampling was by
      identifying key informants and subsequent snowball sampling. Interviews were
      transcribed and main themes identified. RESULTS: Ten interviews were done with
      service providers, including midwives, doctors and nurses. Five main themes were
      identified: characteristics of young people, contraceptive services, positive
      features of Jadelle, barriers to contraception and individual choice. Jadelle was
      seen as a good option due to its effectiveness, discreetness and user
      independence. Barriers for young people obtaining Jadelle included cost, access,
      fear of procedure and lack of appropriate services. CONCLUSION: Health
      professionals had a range of experiences using the contraceptive implant Jadelle.
      Most felt that Jadelle was a good choice for young people. Improvements to access
      were identified, including reduced cost and more youth-friendly services, which
      may lead to increased Jadelle uptake and a subsequent reduction in unintended
      teenage pregnancies.

PMID- 28449014
TI  - Ethnic disparities in the use of seclusion for adult psychiatric inpatients in
      New Zealand.
AB  - AIM: This study aims to investigate disparities in seclusion between Maori and
      non-Maori non-Pacific (nMnP) adults in mental health inpatient units in New
      Zealand. METHOD: This study uses data on 7,239 inpatient psychiatric admissions
      and 782 seclusion events for nine district health boards (servicing 39% of the
      New Zealand population) for the period 1 July 2008 to 30 June 2010, from a New
      Zealand Ministry of Health dataset (PRIMHD). We calculate the age-standardised
      rates of seclusion per monthly inpatient admissions. Regression modelling of
      seclusion event rate ratios for Maori compared to nMnP adjusted for age, gender,
      socioeconomic deprivation (NZDep2006), legal status, referral pathway and
      diagnosis. RESULTS: Maori psychiatric inpatients are 39% more likely to
      experience a seclusion episode than nMnP adults in New Zealand. Important
      contributors to the disparity in seclusion rates between Maori and nMnP were age
      and legal status on admission. Adjustment for a range of demographic and
      admission variables accounted for part of the measured disparity between Maori
      and nMnP (RR 1.33, fully adjusted). CONCLUSIONS: To reduce seclusion use for
      Maori, community mental health services responsive to Maori needs are required to
      prevent the need for inpatient admission, and reduce the acuity of illness where
      admission is required.

PMID- 28449016
TI  - A critical exploration of a collaborative Kaupapa Maori consistent research
      project on physician-assisted dying.
AB  - AIM: This paper critically explores the research approach undertaken by Maori and
      tauiwi researchers working alongside kaumatua within the context of physician
      assisted dying. We critically explore the collaborative process we undertook in
      framing the research context and discuss the rewards and challenges that emerged.
      METHOD: The research this critical discussion draws on undertook a qualitative
      Kaupapa Maori consistent research approach and drew on the principles of an
      Interface Research approach. The paper focuses on the collaborative approach
      taken between the 10 researchers involved in the study. RESULTS: Challenges
      identified within the collaborative Kaupapa Maori consistent research process
      included: determining appropriate authority and representation of researchers and
      participants; maintaining clear communication; time and logistical management.
      The key strengths that emerged from this research design were: establishing a
      culturally safe and robust research process; an ability to build and maintain
      relationships between researchers and participants; and the opportunity to
      develop academic research skills between researchers and participants.
      CONCLUSION: Collaborative Kaupapa Maori consistent research approaches to
      research can enable accountability, control and representation throughout the
      entire research process. Given the rich research results achieved and personal
      rewards gained from this study design, we would advocate for the application of
      such approaches within health research contexts.

PMID- 28449017
TI  - A multifaceted intervention to improve primary care radiology referral quality
      and value in Canterbury.
AB  - AIMS: This article describes a seven-year multifaceted intervention leading to
      sustained improvement in primary care radiology referral quality and value in
      Canterbury, New Zealand, and discusses the transferability to other health
      systems. METHODS: Access criteria were developed with input from general
      practitioners and hospital-based specialists, and embedded in locally developed
      clinical pathways. A referral management service was created to streamline
      referral processes. Systems were developed to enable electronic referral and
      triage, and to provide visibility of prior imaging. A team of general
      practitioners was formed to continually review referrals relative to agreed
      criteria and to provide advice to referrers. Referring general practitioners were
      provided data and education about their referral patterns relative to their
      peers. A clinical audit programme was introduced to ensure quality and safety of
      care. RESULTS: The service achieved sustained improvements in referral quality
      (referral acceptance rates increased from 78% to 88%, urgent referrals reduced
      from 59% to 22%) and value (plain film volumes reduced by 40%). CONCLUSIONS:
      Sustained improvement to primary care radiology referral quality and value is
      achievable at scale using a multifaceted intervention. The transferability of
      this outcome is likely to be connected to supporting factors present in the
      Canterbury health system.

PMID- 28449018
TI  - Accuracy of ethnicity data recorded in hospital-based patient clinical records
      and the Australia and New Zealand Dialysis and Transplant Registry.
AB  - AIM: Sustained health inequities are experienced by indigenous and minority
      populations. Accurate ethnicity data are fundamental to healthcare planning and
      provision and monitoring of health outcomes to address such inequities. This
      study investigated the accuracy of ethnicity data in a large clinical registry of
      end-stage kidney disease patients (the Australia and New Zealand Dialysis and
      Transplant Registry; ANZDATA) and hospital-based patient clinical records
      compared with self-reported ethnicity data collected in the 'Dialysis Outcomes in
      those aged >=65 years' (DOS65+) study. METHODS: Self-reported ethnicity data were
      collected, as per national guidelines, from DOS65+ participants and compared with
      ethnicity data recorded for these participants in ANZDATA and hospital-based
      patient clinical records. Ethnicities were first prioritised and then grouped
      into one of the following: European, Maori, Pacific, Asian and Other. Cohen's
      Kappa statistics were calculated to determine overall non-random agreement.
      Concordances for ethnic group categories were calculated. RESULTS: There was high
      concordance between self-reported ethnicity and ethnicity recorded in both the
      ANZDATA (kappa=0.95) and hospital-based patient clinical records (kappa=0.93).
      Concordances for ethnic group categories between datasets ranged from 86% to
      100%. CONCLUSION: Our findings show a high level of agreement for ethnicity
      recorded for end-stage kidney disease patients between the three datasets,
      suggesting robust data to support health planning and research. Despite this,
      alignment of ethnicity data collection methods, as per national guidelines,
      should occur for all databases used for research and clinical practice in New
      Zealand.

PMID- 28449019
TI  - The clear and present danger of carbapenemase-producing Enterobacteriaceae (CPE)
      in New Zealand: time for a national response plan.
AB  - Antimicrobial resistance (AMR) in general poses a threat to the sustainability of
      modern healthcare, but a particularly urgent and serious threat is posed by a
      specific group of antibiotic-resistant bacteria known as carbapenemase-producing
      Enterobacteriaceae (CPE). CPE are resistant to nearly all antibiotics and include
      common pathogens such as Escherichia coli and Klebsiella pneumoniae. In New
      Zealand, the incidence of CPE has increased from three isolates in 2012 to 45 in
      2016. The current epidemiology of CPE in New Zealand has similarities with the
      extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) epidemic
      in the early 2000s (just before ESBL-PE underwent a non-linear increase in
      incidence). Although to date in New Zealand, nearly all CPE have been imported
      from overseas, this situation appears to be changing, with evidence of secondary
      spread in both households and healthcare facilities over the last year. In this
      article, we argue that CPE should be regarded as the foremost AMR threat
      currently facing New Zealand, and highlight the need for a comprehensive national
      response plan, analogous to plans for other emerging transmissible infections,
      such as pandemic influenza and Ebola. We also make recommendations about the
      components of such a plan and advocate that CPE should be recognised as a key
      priority in New Zealand's national AMR strategy, due to be published in May 2017.

PMID- 28449020
TI  - S pneumoniae purulent pericarditis in the setting of community-acquired
      pneumonia.

PMID- 28449022
TI  - "The iron is hot" for alcohol-related policy changes in New Zealand.

PMID- 28449021
TI  - Scurvy in New Zealand-a forgotten disease.

PMID- 28449023
TI  - Racial Disparities in Blood Pressure Trajectories of Preterm Children: The Role
      of Family and Neighborhood Socioeconomic Status.
AB  - Racial disparities in cardiovascular disease mortality in the United States
      remain substantial. However, the childhood roots of these disparities are not
      well understood. In the current study, we examined racial differences in blood
      pressure trajectories across early childhood in a sample of African-American and
      European-American low-birth-weight preterm infants. Family and neighborhood
      socioeconomic status (SES), measured at baseline, were also examined as
      explanations for subsequent group disparities. Analyses focused on 407 African
      American and 264 European-American children who participated in the Infant Health
      and Development Program, a US longitudinal study of preterm children born in
      1985. Blood pressure was assessed on 6 occasions between the ages of 24 and 78
      months, in 1987-1992. Across this age range, the average rate of change in both
      systolic and diastolic blood pressure was greater among African-American children
      than among European-American children. Neighborhood SES explained 29% and 24% of
      the racial difference in the average rate of change in systolic and diastolic
      blood pressure, respectively, whereas family SES did not account for group
      differences. The findings show that racial differences in blood pressure among
      preterm children emerge in early childhood and that neighborhood SES accounts for
      a portion of racial disparities.

PMID- 28449024
TI  - Secretagogin is Expressed by Developing Neocortical GABAergic Neurons in Humans
      but not Mice and Increases Neurite Arbor Size and Complexity.
AB  - The neocortex of primates, including humans, contains more abundant and diverse
      inhibitory neurons compared with rodents, but the molecular foundations of these
      observations are unknown. Through integrative gene coexpression analysis, we
      determined a consensus transcriptional profile of GABAergic neurons in mid
      gestation human neocortex. By comparing this profile to genes expressed in
      GABAergic neurons purified from neonatal mouse neocortex, we identified conserved
      and distinct aspects of gene expression in these cells between the species. We
      show here that the calcium-binding protein secretagogin (SCGN) is robustly
      expressed by neocortical GABAergic neurons derived from caudal ganglionic
      eminences (CGE) and lateral ganglionic eminences during human but not mouse brain
      development. Through electrophysiological and morphometric analyses, we examined
      the effects of SCGN expression on GABAergic neuron function and form. Forced
      expression of SCGN in CGE-derived mouse GABAergic neurons significantly increased
      total neurite length and arbor complexity following transplantation into mouse
      neocortex, revealing a molecular pathway that contributes to morphological
      differences in these cells between rodents and primates.

PMID- 28449025
TI  - RelTime Rates Collapse to a Strict Clock When Estimating the Timeline of Animal
      Diversification.
AB  - Establishing an accurate timescale for the history of life is crucial to
      understand evolutionary processes. For this purpose, relaxed molecular clock
      models implemented in a Bayesian MCMC framework are generally used. However,
      these methods are time consuming. RelTime, a non-Bayesian method implementing a
      fast, ad hoc, algorithm for relative dating, was developed to overcome the
      computational inefficiencies of Bayesian software. RelTime was recently used to
      investigate the timing of origin of animals, yielding results consistent with
      early strict clock studies from the 1980s and 1990s, estimating metazoans to have
      a Mesoproterozoic origin-over a billion years ago. RelTime results are unexpected
      and disagree with the largest majority of modern, relaxed, Bayesian molecular
      clock analyses, which suggest animals originated in the Tonian-Cryogenian (less
      that 850 million years ago). Here, we demonstrate that RelTime-inferred
      divergence times for the origin of animals are spurious, a consequence of the
      inability of RelTime to relax the clock along the internal branches of the animal
      phylogeny. RelTime-inferred divergence times are comparable to strict-clock
      estimates because they are essentially inferred under a strict clock. Our results
      warn us of the danger of using ad hoc algorithms making implicit assumptions
      about rate changes along a tree. Our study roundly rejects a Mesoproterozoic
      origin of animals; metazoans emerged in the Tonian-Cryogenian, and diversified in
      the Ediacaran, in the immediate prelude to the routine fossilization of animals
      in the Cambrian associated with the emergence of readily preserved skeletons.

PMID- 28449026
TI  - Guanine quadruplex structures localize to heterochromatin.

PMID- 28449027
TI  - Lipoprotein(a) and the risk of cardiovascular disease in the European population:
      results from the BiomarCaRE consortium.
AB  - Aims: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the
      need for a precise characterization and comparability of the Lp(a)-associated
      cardiovascular risk is increasing. Therefore, we aimed to evaluate the
      distribution of Lp(a) concentrations across the European population, to
      characterize the association with cardiovascular outcomes and to provide high
      comparability of the Lp(a)-associated cardiovascular risk by use of centrally
      determined Lp(a) concentrations. Methods and results: Based on the Biomarkers for
      Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data
      of 56 804 participants from 7 prospective population-based cohorts across Europe
      with a maximum follow-up of 24 years. All Lp(a) measurements were performed in
      the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott
      Diagnostics). The three endpoints considered were incident major coronary events
      (MCE), incident cardiovascular disease (CVD) events, and total mortality. We
      found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared
      to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL)
      (Jonckheere-Terpstra test P < 0.001). Kaplan-Meier curves showed the highest
      event rate of MCE and CVD events for Lp(a) levels >=90th percentile (log-rank
      test: P < 0.001 for MCE and CVD). Cox regression models adjusted for age, sex,
      and cardiovascular risk factors revealed a significant association of Lp(a)
      levels with MCE and CVD with a hazard ratio (HR) of 1.30 for MCE [95% confidence
      interval (CI) 1.15-1.46] and of 1.25 for CVD (95% CI 1.12-1.39) for Lp(a) levels
      in the 67-89th percentile and a HR of 1.49 for MCE (95% CI 1.29-1.73) and of 1.44
      for CVD (95% CI 1.25-1.65) for Lp(a) levels >= 90th percentile vs. Lp(a) levels
      in the lowest third (P < 0.001 for all). There was no significant association
      between Lp(a) levels and total mortality. Subgroup analysis for a continuous
      version of cube root transformed Lp(a) identified the highest Lp(a)-associated
      risk in individuals with diabetes [HR for MCE 1.31 (95% CI 1.15-1.50)] and for
      CVD 1.22 (95% CI 1.08-1.38) compared to those without diabetes [HR for MCE 1.15
      (95% CI 1.08-1.21; HR for CVD 1.13 (1.07-1.19)] while no difference of the Lp(a)-
      associated risk were seen for other cardiovascular high risk states. The addition
      of Lp(a) levels to a prognostic model for MCE and CVD revealed only a marginal
      but significant C-index discrimination measure increase (0.001 for MCE and CVD; P
      < 0.05) and net reclassification improvement (0.010 for MCE and 0.011 for CVD).
      Conclusion: In this large dataset on harmonized Lp(a) determination, we observed
      regional differences within the European population. Elevated Lp(a) was robustly
      associated with an increased risk for MCE and CVD in particular among individuals
      with diabetes. These results may lead to better identification of target
      populations who might benefit from future Lp(a)-lowering therapies.

PMID- 28449028
TI  - Surgical therapy of thymic tumours with pleural involvement: an ESTS Thymic
      Working Group Project.
AB  - OBJECTIVES: Surgery for thymic epithelial tumours (TETs) with pleural involvement
      is infrequently performed. Thus, the value of surgical therapy for primary or
      recurrent TETs with pleural involvement is not sufficiently defined yet. METHODS:
      Twelve institutions contributed retrospective data on 152 patients undergoing
      surgery (1977-2014) on behalf of the ESTS Thymic Working group. Outcome measures
      included overall (OS), cause-specific (CSS) and disease-free (DFS) survival as
      well as freedom from recurrence (FFR). RESULTS: In 70.4% of cases, pleural
      involvement was present at the time of primary intervention, whereas 29.6% had
      surgery for recurrent disease involving the pleura. Pleural involvement resulted
      from thymomas (88.8%) and thymic carcinomas (11.2%). Forty extrapleural
      pneumonectomies (EPPs), 23 total pleurectomies (TPs), and 88 local pleurectomies
      (LPs) were performed (completeness of resection in 76.8%). OS for the entire
      patient population at 1, 3, 5 and 10 years was 96.4%, 91.0%, 87.2% and 62.7%,
      respectively. There was no statistically significant difference regarding FFR and
      OS for patients with local or advanced disease undergoing EPP, TP or LP. Thymic
      carcinomas in comparison with thymomas had a negative impact on OS [hazard ratio
      6.506, P  = 0.002], CSS and FFR. Incomplete resections predicted worse OS [hazard
      ratio 6.696, P  = 0.003]. CONCLUSIONS: Complete resection remains the mainstay of
      treatment for TETs with pleural involvement. Study populations treated with EPP,
      TP and LP had similar survival that may be factual as observed, but in the
      presence of selection bias, we can further conclude from the results that EPP, TP
      and LP are equally effective procedures. Procedural choice depends upon the
      extent of tumour distribution. EPPs, TPs and LPs performed within a multimodality
      setting seem to be efficient procedures for local control of disease, as they
      yield excellent results regarding OS, DFS, CSS and FFR.

PMID- 28449029
TI  - A genome-wide association study identifies nucleotide variants at SIGLEC5 and
      DEFA1A3 as risk loci for periodontitis.
AB  - Periodontitis is one of the most common inflammatory diseases, with a prevalence
      of 11% worldwide for the severe forms and an estimated heritability of 50%. The
      disease is characterized by destruction of the alveolar bone due to an aberrant
      host inflammatory response to a dysbiotic oral microbiome. Previous genome-wide
      association studies (GWAS) have reported several suggestive susceptibility loci.
      Here, we conducted a GWAS using a German and Dutch case-control sample of
      aggressive periodontitis (AgP, 896 cases, 7,104 controls), a rare but highly
      severe and early-onset form of periodontitis, validated the associations in a
      German sample of severe forms of the more moderate phenotype chronic
      periodontitis (CP) (993 cases, 1,419 controls). Positive findings were replicated
      in a Turkish sample of AgP (223 cases, 564 controls). A locus at SIGLEC5 (sialic
      acid binding Ig-like lectin 5) and a chromosomal region downstream of the DEFA1A3
      locus (defensin alpha 1-3) showed association with both disease phenotypes and
      were associated with periodontitis at a genome-wide significance level in the
      pooled samples, with P = 1.09E-08 (rs4284742,-G; OR = 1.34, 95% CI = 1.21-1.48)
      and P = 5.48E-10 (rs2738058,-T; OR = 1.28, 95% CI = 1.18-1.38), respectively.
      SIGLEC5 is expressed in various myeloid immune cells and classified as an
      inhibitory receptor with the potential to mediate tyrosine phosphatases SHP-1/-2
      dependent signaling. Alpha defensins are antimicrobial peptides with expression
      in neutrophils and mucosal surfaces and a role in phagocyte-mediated host
      defense. This study identifies the first shared genetic risk loci of AgP and CP
      with genome-wide significance and highlights the role of innate and adaptive
      immunity in the etiology of periodontitis.

PMID- 28449030
TI  - Spillover effects on health outcomes in low- and middle-income countries: a
      systematic review.
AB  - Background: Many interventions delivered to improve health may benefit not only
      direct recipients but also people in close physical or social proximity. Our
      objective was to review all published literature about the spillover effects of
      interventions on health outcomes in low-middle income countries and to identify
      methods used in estimating these effects. Methods: We searched 19 electronic
      databases for articles published before 2014 and hand-searched titles from 2010
      to 2013 in five relevant journals. We adapted the Cochrane Collaboration's
      quality grading tool for spillover estimation and rated the quality of evidence.
      Results: A total of 54 studies met inclusion criteria. We found a wide range of
      terminology used to describe spillovers, a lack of standardization among
      spillover methods and poor reporting of spillovers in many studies. We identified
      three primary mechanisms of spillovers: reduced disease transmission, social
      proximity and substitution of resources within households. We found the strongest
      evidence for spillovers through reduced disease transmission, particularly
      vaccines and mass drug administration. In general, the proportion of a population
      receiving an intervention was associated with improved health. Most studies were
      of moderate or low quality. We found evidence of publication bias for certain
      spillover estimates but not for total or direct effects. To facilitate improved
      reporting and standardization in future studies, we developed a reporting
      checklist adapted from the CONSORT framework specific to reporting spillover
      effects. Conclusions: We found the strongest evidence for spillovers from
      vaccines and mass drug administration to control infectious disease. There was
      little high quality evidence of spillovers for other interventions.

PMID- 28449031
TI  - RNAblueprint: flexible multiple target nucleic acid sequence design.
AB  - Motivation: Realizing the value of synthetic biology in biotechnology and
      medicine requires the design of molecules with specialized functions. Due to its
      close structure to function relationship, and the availability of good structure
      prediction methods and energy models, RNA is perfectly suited to be synthetically
      engineered with predefined properties. However, currently available RNA design
      tools cannot be easily adapted to accommodate new design specifications.
      Furthermore, complicated sampling and optimization methods are often developed to
      suit a specific RNA design goal, adding to their inflexibility. Results: We
      developed a C ++  library implementing a graph coloring approach to
      stochastically sample sequences compatible with structural and sequence
      constraints from the typically very large solution space. The approach allows to
      specify and explore the solution space in a well defined way. Our library also
      guarantees uniform sampling, which makes optimization runs performant by not only
      avoiding re-evaluation of already found solutions, but also by raising the
      probability of finding better solutions for long optimization runs. We show that
      our software can be combined with any other software package to allow diverse RNA
      design applications. Scripting interfaces allow the easy adaption of existing
      code to accommodate new scenarios, making the whole design process very flexible.
      We implemented example design approaches written in Python to demonstrate these
      advantages. Availability and implementation: RNAblueprint , Python
      implementations and benchmark datasets are available at github:
      https://github.com/ViennaRNA . Contact: s.hammer@univie.ac.at,
      ivo@tbi.univie.ac.at or sven@tbi.univie.ac.at. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 28449032
TI  - Comparing Outcomes and Cost of 3 Surgical Treatments for Sagittal Synostosis: A
      Retrospective Study Including Procedure-Related Cost Analysis.
AB  - BACKGROUND: Neurosurgical techniques for repair of sagittal synostosis include
      total cranial vault (TCV) reconstruction, open sagittal strip (OSS) craniectomy,
      and endoscopic strip (ES) craniectomy. OBJECTIVE: To evaluate outcomes and cost
      associated with these 3 techniques. METHODS: Via retrospective chart review with
      waiver of informed consent, the last consecutive 100 patients with sagittal
      synostosis who underwent each of the 3 surgical correction techniques before June
      30, 2013, were identified. Clinical, operative, and process of care variables and
      their associated specific charges were analyzed along with overall charge.
      RESULTS: The study included 300 total patients. ES patients had fewer transfusion
      requirements (13% vs 83%, P < .001) than TCV patients, fewer days in intensive
      care (0.3 vs 1.3, P < .001), and a shorter overall hospital stay (1.8 vs 4.2 d, P
      < .001), and they required fewer revisions (1% vs 6%, P = .05). The mean charge
      for the endoscopic procedure was $21 203, whereas the mean charge for the TCV
      reconstruction was $45 078 (P < .001). ES patients had more preoperative computed
      tomography scans (66% vs 44%, P = .003) than OSS patients, shorter operative
      times (68 vs 111 min, P < .001), and required fewer revision procedures (1% vs
      8%, P < .001). The mean charge for the endoscopic procedure was $21 203 vs $20
      535 for the OSS procedure (P = .62). CONCLUSION: The ES craniectomy for sagittal
      synostosis appeared to have less morbidity and a potential cost savings compared
      with the TCV reconstruction. The charges were similar to those incurred with OSS
      craniectomy, but patients had a shorter length of stay and fewer revisions.

PMID- 28449034
TI  - Parental break-ups and stress: roles of age & family structure in 44 509 pre
      adolescent children.
AB  - Background: Parental break-up is wide spread, and the effects of parental break
      up on children's well-being are known. The evidence regarding child age at break
      up and subsequent family arrangements is inconclusive. Aim: to estimate the
      effects of parental break-up on stress in pre-adolescent children with a specific
      focus on age at break-up and post-breakup family arrangements. Methods: We used
      data from the Danish National Birth Cohort. Participants included 44 509 children
      followed from birth to age 11. Stress was self-reported by children at age 11,
      when the children also reported on parental break-up and post break-up family
      arrangements. Results: Twenty-one percent of the children had experienced a
      parental break-up at age 11, and those who had experienced parental break-up
      showed a higher risk of stress (OR:1.72, 95%CI:1.55;1.91) regardless of the
      child's age at break-up. Children living in a new family with stepparents (OR =
      1.63, 95%CI:1.38;1.92), or shared between the parents (OR = 1.48,
      95%CI:1.26;1.75) reported higher stress than children of intact families. Single
      parent families reported markedly higher stress levels than children in intact
      families (OR = 2.18, 95%CI:1.90;2.50) and all other family types. Children who
      were satisfied with their living arrangements post-break-up reported the same
      stress level as children living in intact families (OR = 1.01, 95%CI:0.86;1.18).
      Conclusion: Children who experience parental break-up have higher stress levels,
      also many years after the break-up, and those living in a single parent household
      post break-up seem to be most vulnerable. Living arrangements post-breakup should
      be further investigated as a potential protective factor.

PMID- 28449033
TI  - Response assessment in medulloblastoma and leptomeningeal seeding tumors:
      recommendations from the Response Assessment in Pediatric Neuro-Oncology
      committee.
AB  - Lack of standard response criteria in clinical trials for medulloblastoma and
      other seeding tumors complicates assessment of therapeutic efficacy and
      comparisons across studies. An international working group was established to
      develop consensus recommendations for response assessment. The aim is that these
      recommendations be prospectively evaluated in clinical trials, with the goal of
      achieving more reliable risk stratification and uniformity across clinical
      trials. Current practices and literature review were performed to identify major
      confounding issues and justify subsequently developed recommendations; in areas
      lacking scientific investigations, recommendations were based on experience of
      committee members and consensus was reached after discussion. Recommendations
      apply to both adult and pediatric patients with medulloblastoma and other seeding
      tumors. Response should be assessed using MR imaging (brain and spine), CSF
      cytology, and neurologic examination. Clinical imaging standards with minimum
      mandatory sequence acquisition that optimizes detection of leptomeningeal
      metastases are defined. We recommend central review prior to inclusion in
      treatment cohorts to ensure appropriate risk stratification and cohort inclusion.
      Consensus recommendations and response definitions for patients with
      medulloblastomas and other seeding tumors have been established; as with other
      Response Assessment in Neuro-Oncology recommendations, these need to now be
      prospectively validated in clinical trials.

PMID- 28449035
TI  - Identification and Expression Profiling of Odorant-Binding Proteins and
      Chemosensory Proteins of Daktulosphaira vitifoliae (Hemiptera: Phylloxeridae).
AB  - In insects, odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are
      primary peripheral olfactory proteins playing critical roles in odorant
      detection. In this study, we present the first identification of OBPs and CSPs
      from the transcriptome of grape phylloxera Daktulosphaira vitifoliae Fitch, an
      important pest that damages both roots and leaves of grapes. The OBPs contained
      six conserved cysteine residues and the CSPs contained four conserved cysteine
      residues in this insect. Phylogenetic analysis showed that most of the olfactory
      proteins were closely related to OBPs and CSPs from other aphids. However,
      DviOBP7 and DviCSP9 were different because they were classified into different
      independent branches, respectively. Real-time polymerase chain reaction (RT-PCR)
      was used to examine the tissue expression of these transcripts. DviOBP1, DviOBP6,
      and DviOBP7 were uniquely or primarily expressed in antennae and not in the body.
      DviOBP2 was more abundantly expressed in the body than in the antennae. The
      expression levels of OBPs and CSPs of phylloxera varied depending upon where they
      were expressed in different body tissues.

PMID- 28449037
TI  - Commentary on: Cosmetic Liposuction: Preoperative Risk Factors, Major
      Complication Rates, and Safety of Combined Procedures.

PMID- 28449036
TI  - Resting connectivity between salience nodes predicts recognition memory.
AB  - The resting connectivity of the brain's salience network, particularly the
      ventral subsystem of the salience network, has been previously associated with
      various measures of affective reactivity. Numerous studies have demonstrated that
      increased affective arousal leads to enhanced consolidation of memory. This
      suggests that individuals with greater ventral salience network connectivity will
      exhibit greater responses to affective experience, leading to a greater
      enhancement of memory by affect. To test this hypothesis, resting ventral
      salience connectivity was measured in 41 young adults, who were then exposed to
      neutral and negative affect inductions during a paired associate memory test.
      Memory performance for material learned under both negative and neutral induction
      was tested for correlation with resting connectivity between major ventral
      salience nodes. The results showed a significant interaction between mood
      induction (negative vs neutral) and connectivity between ventral anterior insula
      and pregenual anterior cingulate cortex, indicating that salience node
      connectivity predicted memory for material encoded under negative, but not
      neutral induction. These findings suggest that the network state of the
      perceiver, measured prior to affective experience, meaningfully influences the
      extent to which affect modulates memory. Implications of these findings for
      individuals with affective disorder, who show alterations in both connectivity
      and memory, are considered.

PMID- 28449038
TI  - Real-time imaging of single neuronal cell apoptosis in patients with glaucoma.
AB  - See Herms and Schon (doi10.1093/brain/awx100) for a scientific commentary on this
      article.: 

PMID- 28449039
TI  - Polyphyllin I induces G2/M phase arrest and apoptosis in U251 human glioma cells
      via mitochondrial dysfunction and the JNK signaling pathway.
AB  - Glioblastoma is the most aggressive brain tumor, and its prognosis remains poor.
      Therefore, novel therapeutic strategies are needed for glioma therapy.
      Polyphyllin I (PPI), a bioactive constituent extracted from Paris polyphylla, was
      reported to have anti-tumor activity. However, the detailed mechanism for this
      activity remains unclear. Here, we investigated the inhibitory effects of PPI on
      glioma cells and its mechanisms in vitro. U251 cells were treated with various
      concentrations of PPI (2-9 MUM) for 24 to 72 h. The inhibition of U251 cell
      proliferation by PPI was assessed by MTT assay. The effects on cell cycle and
      apoptosis were examined by flow cytometry with PI and annexin V-FITC/PI dual
      staining, and the cell mitochondrial membrane potential level was evaluated by
      fluorescence microscopy with JC-1 staining. The expression levels of apoptosis
      related proteins and JNK signal pathway proteins were evaluated by western blot
      analysis. Results showed that PPI significantly inhibited the proliferation of
      U251 cells in a concentration-dependent manner. PPI induced G2/M phase arrest and
      apoptosis, and it upregulated the expressions of Bax, cytochrome c, and p-JNK,
      but downregulated the expression of the anti-apoptotic protein Bcl-2 in U251
      cells. Moreover, PPI provoked the depolarization of the mitochondrial membrane
      potential. In addition, apoptosis induced by the PPI was remarkably suppressed by
      the JNK inhibitor SP600125. Our data provide evidence that PPI inhibits
      proliferation and induces apoptotic cell death in U251 cells. This effect may be
      associated with the JNK pathway. These results suggest that PPI is an activator
      of the JNK signaling pathway with a potential anti-glioma effect.

PMID- 28449040
TI  - Toxin-antitoxin systems and their role in disseminating and maintaining
      antimicrobial resistance.
AB  - Toxin-antitoxin systems (TAs) are ubiquitous among bacteria and play a crucial
      role in the dissemination and evolution of antibiotic resistance, such as
      maintaining multi-resistant plasmids and inducing persistence formation.
      Generally, activities of the toxins are neutralised by their conjugate
      antitoxins. In contrast, antitoxins are more liable to degrade under specific
      conditions such as stress, and free active toxins interfere with essential
      cellular processes including replication, translation and cell-wall synthesis.
      TAs have also been shown to be responsible for plasmid maintenance, stress
      management, bacterial persistence and biofilm formation. We discuss here the
      recent findings of these multifaceted TAs (type I-VI) and in particular examine
      the role of TAs in augmenting the dissemination and maintenance of multi-drug
      resistance in bacteria.

PMID- 28449042
TI  - Long noncoding RNA: a crosslink in biological regulatory network.
AB  - Long noncoding RNAs (lncRNAs) had been defined as a novel class of functional
      RNAs longer than 200 nucleotides around a decade ago. It is widely acknowledged
      that lncRNAs play a significant role in regulation of gene expression, but the
      biological and molecular mechanisms are diverse and complex, and remain to be
      determined. Especially, the regulatory network of lncRNAs associated with other
      biological molecules is still a controversial matter, thus becoming a new
      frontier of the studies on transcriptome. Recent advance in high-throughput
      sequencing technologies and bioinformatics approaches may be an accelerator to
      lift the mysterious veil. In this review, we will outline well-known associations
      between lncRNAs and other biological molecules, demonstrate the diverse
      bioinformatics approaches applied in prediction and analysis of lncRNA
      interaction and perform a case study for lncRNA linc00460 to concretely decipher
      the lncRNA regulatory network.

PMID- 28449041
TI  - Periodontal Disease, Tooth Loss, and Cancer Risk.
AB  - Periodontal disease, which includes gingivitis and periodontitis, is highly
      prevalent in adults and disease severity increases with age. The relationship
      between periodontal disease and oral cancer has been examined for several
      decades, but there is increasing interest in the link between periodontal disease
      and overall cancer risk, with systemic inflammation serving as the main focus for
      biological plausibility. Numerous case-control studies have addressed the role of
      oral health in head and neck cancer, and several cohort studies have examined
      associations with other types of cancers over the past decade. For this review,
      we included studies that were identified from either 11 published reviews on this
      topic or an updated literature search on PubMed (between 2011 and July 2016). A
      total of 50 studies from 46 publications were included in this review. Meta
      analyses were conducted on cohort and case-control studies separately when at
      least 4 studies could be included to determine summary estimates of the risk of
      cancer in relation to 1) periodontal disease or 2) tooth number (a surrogate
      marker of periodontal disease) with adjustment for smoking. Existing data provide
      support for a positive association between periodontal disease and risk of oral,
      lung, and pancreatic cancers; however, additional prospective studies are needed
      to better inform on the strength of these associations and to determine whether
      other cancers are associated with periodontal disease. Future studies should
      include sufficiently large sample sizes, improved measurements for periodontal
      disease, and thorough adjustment for smoking and other risk factors.

PMID- 28449044
TI  - Vernakalant does not alter early repolarization or contractility in normal and
      electrically remodelled atria.
AB  - Aims: Besides the inhibition of the sodium inward current, vernakalant also
      inhibits the ultra rapid rectifier (IKur) and transient outward current (Ito).
      Inhibition of these currents increases contractility in canine atrial myocytes
      and goat atria. We investigated the effect of vernakalant on early repolarization
      and contractility in normal and electrically remodelled atria. Methods and
      results: Goats were implanted a pressure catheter, piezoelectric crystals, and
      electrodes to obtain atrial contractility and effective refractory period (ERP).
      The active component in pressure distance loops was used to compute the atrial
      work index (AWI). Experiments were performed in normal and electrically
      remodelled atria at clinically relevant plasma levels of vernakalant. As a
      positive control, the Ito/IKur blocker AVE0118 was investigated. Monophasic
      action potentials were recorded in anaesthetized goats and in explanted hearts to
      determine changes in action potential morphology. Vernakalant did not affect
      atrial work loops during sinus rhythm. Likewise vernakalant did not increase
      atrial fractional shortening or AWI during pacing with fixed heart rate and AV
      delay. In contrast, AVE0118 did increase AWI, with a positive force frequency
      relation. Both in normal and remodelled atria, vernakalant strongly increased ERP
      but did not prolong early repolarization. Conclusion: In goat atria, vernakalant
      does not have an atrial positive inotropic effect and does not affect early
      repolarization. At high rates vernakalant may even have a negative inotropic
      effect.

PMID- 28449045
TI  - The relationship between self-reported health status and signs of psychological
      distress within European urban contexts.
AB  - Background: Self-reported health status (SRHS) reflects an individual's
      perception of their social, biological and psychological health, and has been
      linked to increased mortality risk and increased use of health services. Having a
      psychological co-morbidity can reduce health outcomes and increase healthcare
      costs. This paper investigates the relationship between SRHS and signs of
      psychological distress (PD) in European urban settings. The study sample
      comprised 20 439 adult respondents to surveys conducted across 37 urban areas.
      Data on SRHS, signs of PD and potential confounders were analysed in a
      multivariable logistic regression. After adjusting for potential confounders
      (gender, age, time lived in country and regularity of contact with family and
      friends), a significant association was found between PD and self-reported poor
      health for all urban areas, particularly in Western European countries (adjusted
      OR = 3.615, 95% CI: 3.333-3.920 P < 0.001). Time lived in country of residence,
      financial stability and regularity of contact with family and friends were
      negatively associated with signs of PD in the adjusted model. There is a
      statistically significant association between self-reported poor health and signs
      of PD. Although the relationship was present in all geographical locations, the
      confounders were protective factors for Western European countries. Since the two
      factors are linked, interventions that target one might reduce the impact on
      both. Further study into causality would be of use in predicting future
      healthcare costs, which could be reduced by integrating their management.

PMID- 28449043
TI  - Potent DNA strand annealing activity associated with mouse Mcm2~7 heterohexameric
      complex.
AB  - Mini-chromosome maintenance (Mcm) is a central component for DNA unwinding
      reaction during eukaryotic DNA replication. Mcm2~7, each containing a conserved
      ATPase motif, form a six subunit-heterohexamer. Although the reconstituted Mcm2~7
      Cdc45-GINS (CMG) complex displays DNA unwinding activity, the Mcm2~7 complex does
      not generally exhibit helicase activity under a normal assay condition. We
      detected a strong DNA strand annealing activity in the purified mouse Mcm2~7
      heterohexamer, which promotes rapid reassociation of displaced complementary
      single-stranded DNAs, suggesting a potential cause for its inability to exhibit
      DNA helicase activity. Indeed, DNA unwinding activity of Mcm2~7 could be detected
      in the presence of a single-stranded DNA that is complementary to the displaced
      strand, which would prevent its reannealing to the template. ATPase-deficient
      mutations in Mcm2, 4, 5 and 6 subunits inactivated the annealing activity, while
      those in Mcm2 and 5 subunits alone did not. The annealing activity of Mcm2~7 does
      not require Mg2+ and ATP, and is adversely inhibited by the presence of high
      concentration of Mg2+ and ATP while activated by similar concentrations of ADP.
      Our findings show that the DNA helicase activity of Mcm2~7 may be masked by its
      unexpectedly strong annealing activity, and suggest potential physiological roles
      of strand annealing activity of Mcm during replication stress responses.

PMID- 28449046
TI  - Prone positioning as a bridge to recovery from refractory hypoxaemia following
      lung transplantation.
AB  - OBJECTIVES: Refractory hypoxaemia is the leading cause of mortality in the
      postoperative period after lung transplantation. The role of prone positioning as
      a rescue therapy in this setting has not been assessed. We evaluated its effects
      in lung transplant recipients presenting refractory hypoxaemia following the
      surgery. METHODS: Prospectively collected data from 131 consecutive adult
      patients undergoing lung transplantation between January 2013 and December 2014
      were evaluated. Twenty-two patients received prone position therapy. Indications,
      associated complications, time to initiation and duration of the manoeuvre were
      analysed and the effects of prone position on gas exchange were evaluated.
      Finally, outcomes in this cohort were compared against the rest of lung
      transplant recipients. RESULTS: Prone positioning was more frequently implemented
      within the first 72 h (68.2%) and its main indication was primary graft
      dysfunction. The manoeuvre was maintained during a median of 21 h. After prone
      position, the pressure of arterial oxygen/fraction of inspired oxygen ratio
      significantly increased from 81.0 mmHg [interquartile range (IQR) 71.5-104.0] to
      220.0 (IQR 160.0-288.0) (P < 0.001). No complications related with the technique
      were reported. Patients who underwent the manoeuvre had longer hospital stay
      [50.0 days (IQR 36.0-67.0) vs 30.0 (IQR 23.0-56.0), P = 0.006] than the rest of
      the population. No differences were found comparing either 1-year mortality (9.1%
      vs 15.6%; P = 0.740) or 1-year graft function [forced expiratory volume in 1
      second of 70.0 (IQR 53.0-83.0) vs 68.0 (IQR 53.5-80.5), P = 0.469]. CONCLUSIONS:
      Prone positioning is safe and significantly improves gas exchange in patients
      with refractory hypoxaemia after lung transplantation. It should be considered as
      a possible treatment in these patients.

PMID- 28449047
TI  - What's buzzing on your feed? Health authorities' use of Facebook to combat Zika
      in Singapore.
AB  - In 2016, Singapore grappled with one of the largest Zika outbreaks in Southeast
      Asia. This study examines the use of Facebook for Zika-related outreach by the
      Ministry of Health (MOH) and the National Environmental Agency (NEA) from March
      1, 2015, to September 1, 2016, and public response to this effort. Despite nearly
      equivalent outreach, MOH's Facebook posts received more likes (u = 3.49) and
      shares (u = 30.11), whereas NEA's posts received more comments (u = 4.55), with
      NEA posting mostly on prevention (N = 30) and MOH on situational updates (N =
      24). Thematic analyses identified prevention-related posts as garnering the most
      likes (N = 1277), while update-related posts were most shared (N = 1059) and
      commented upon (N = 220). Outreach ceased briefly for 2 months after Singapore's
      first imported case of Zika, but increased following the outbreak of locally
      transmitted cases in August 2016. Public engagement was significantly higher
      during Zika compared with prior haze and dengue outbreaks. The results indicate
      the value of Facebook as a tool for rapid outreach during infectious disease
      outbreaks, and as a "listening" platform for those managing the situation. We
      discuss implications for public health communication research and policy.

PMID- 28449048
TI  - Spot sign, prognosis and intracerebral haemorrhage.

PMID- 28449049
TI  - Professional burnout in European young oncologists: results of the European
      Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey.
AB  - Background: Burnout in health care professionals could have serious negative
      consequences on quality of patient care, professional satisfaction and personal
      life. Our aim was to investigate the burnout prevalence, work and lifestyle
      factors potentially affecting burnout amongst European oncologists <=40 (YOs).
      Methods: A survey was conducted using the validated Maslach Burnout Inventory
      (MBI) and additional questions exploring work/lifestyle factors. Statistical
      analyses were carried out to identify factors associated with burnout. Results:
      Total of 737 surveys (all ages) were collected from 41 European countries.
      Countries were divided into six regions. Results from 595 (81%) YOs were included
      (81% medical oncologists; 52% trainees, 62% women). Seventy-one percent of YOs
      showed evidence of burnout (burnout subdomains: depersonalization 50%; emotional
      exhaustion 45; low accomplishment 35%). Twenty-two percent requested support for
      burnout during training and 74% reported no hospital access to support services.
      Burnout rates were significantly different across Europe (P < 0.0001). Burnout
      was highest in central European (84%) and lowest in Northern Europe (52%).
      Depersonalization scores were higher in men compared with women (60% versus 45% P
      = 0.0001) and low accomplishment was highest in the 26-30 age group (P < 0.01).
      In multivariable linear regression analyses, European region, work/life balance,
      access to support services, living alone and inadequate vacation time remained
      independent burnout factors (P < 0.05). Conclusions: This is the largest burnout
      survey in European Young Oncologists. Burnout is common amongst YOs and rates
      vary across Europe. Achieving a good work/life balance, access to support
      services and adequate vacation time may reduce burnout levels. Raising awareness,
      support and interventional research are needed.

PMID- 28449050
TI  - CardioScape mapping the cardiovascular funding landscape in Europe.
AB  - Aims: The burden of cardiovascular disease is increasing worldwide, which has to
      be reflected by cardiovascular (CV) research in Europe. CardioScape, a FP7 funded
      project initiated by the European Society of Cardiology (ESC), identified where
      CV research is performed, how it is funded and by whom. It could be transformed
      into an on-line and up-to-date resource of great relevance for researchers,
      funding bodies and policymakers and could be a role model for mapping CV research
      funding in Europe and beyond. Methods and results: Relevant funding bodies in 28
      European Union (EU) countries were identified by a multistep process involving
      experts in each country. Projects above a funding threshold of 100 k? during the
      period 2010-2012 were included using a standard questionnaire. Results were
      classified by experts and an adaptive text analysis software to a CV-research
      taxonomy, integrating existing schemes from ESC journals and congresses. An on
      line query portal was set up to allow different users to interrogate the database
      according to their specific viewpoints. Conclusion: CV-research funding varies
      strongly between different nations with the EU providing 37% of total available
      project funding and clear geographical gradients exist. Data allow in depth
      comparison of funding for different research areas and led to a number of
      recommendations by the consortium. CardioScape can support CV research by aiding
      researchers, funding agencies and policy makers in their strategic decisions thus
      improving research quality if CardioScape strategy and technology becomes the
      basis of a continuously updated and expanded European wide publicly accessible
      database.

PMID- 28449051
TI  - Viral Kinetics in Semen With Different Antiretroviral Families in Treatment-Naive
      Human Immunodeficiency Virus-Infected Patients: A Randomized Trial.
AB  - Background: There are several regimens for starting antiretroviral treatment, but
      it remains unknown whether either of them is more advantageous regarding the time
      course and magnitude of human immunodeficiency virus (HIV) RNA decay in semen.
      Objective: To evaluate the differential effect of different antiretroviral drug
      families on viral kinetics in seminal plasma (SP) of treatment-naive HIV-infected
      patients. Methods: Phase II, randomized, open-label study in which participants
      were randomized 1:1:1 to receive tenofovir-disoproxil fumarate (DF) plus
      emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine
      (RPV), or ritonavir-boosted darunavir (DRVrtv). The primary endpoint was the
      proportion of participants with undetectable HIV-RNA in SP at week 12. HIV type 1
      (HIV-1) RNA was measured in paired SP and blood plasma (BP) at baseline and after
      1, 2, 4, 6, 8, 12, 18, and 24 weeks. Elvitegravir (EVG), RPV, and darunavir (DRV)
      concentrations were quantified by the liquid chromatography-tandem mass
      spectrometry method. Results: In SP, the HIV-RNA decay rate with RPV was as fast
      as with EVGcobi; by week 12, all participants in the RPV and the EVGcobi groups
      reached an undetectable viral load but only 58.3% in the DRVrtv arm (P = .003).
      The highest SP/BP drug concentration ratio was for EVG (0.43), followed-up by RPV
      (0.19), and DRV (0.10). For both EVG and RPV, the SP concentrations exceeded >2
      fold the protein binding-adjusted EC90 for wild-type HIV-1; for DRV, only 33.7%
      of the SP showed concentrations above the protein binding-adjusted EC90.
      Conclusions: In SP, both RPV and EVGcobi, associated to tenofovir-DF and
      emtricitabine, behave similarly and achieve an undetectable viral load much
      faster than DRVrtv. Registration: European Medical Agency (No. EudraCT: 2014
      001348-39).

PMID- 28449052
TI  - Implementation of a Postoperative Outpatient Care Pathway for Delayed
      Hyponatremia Following Transsphenoidal Surgery.
AB  - BACKGROUND: After transsphenoidal surgery, delayed hyponatremia (DH) is the
      leading cause of 30-d unplanned hospital readmissions. OBJECTIVE: To determine
      the impact of a DH care pathway on 30-d readmissions after transsphenoidal
      surgery. METHODS: Data from before and after DH care pathway implementation were
      retrospectively reviewed. Patient demographics and clinical characteristics were
      compared. Readmission causes, clinical pathway failures, sodium trends, and
      symptoms were evaluated. RESULTS: Before the DH care pathway implementation, 229
      (55%) patients were treated (group 1); afterward, 188 (45%) were treated (group
      2). Baseline characteristics were equivalent between groups, except for
      glucocorticoid supplementation, which was higher in group 2. The incidence of
      detected DH was significantly lower in group 1 (16/229, 7%) than group 2 (29/188,
      15%) (P = .006) likely due to the impact of routine screening in group 2. Ten
      group 1 patients (4%) were readmitted for hyponatremia and 6 (3%) were managed as
      outpatients. Eleven group 2 patients (6%) were readmitted and 17 (9%) were
      managed as outpatients. Readmission rates between groups were similar (P = .49).
      Patients readmitted with severe hyponatremia experienced symptoms >=24 h before
      presentation. The protocol failed to prevent readmission because outpatient
      management for mild or moderate DH (n = 4) failed, sodium levels precipitously
      declined after normal screening (n = 3), and severe hyponatremia developed after
      scheduled screenings were missed (n = 3). CONCLUSION: Although more DH patients
      were identified after care pathway implementation, readmission rates were not
      reduced and clinical outcomes were not changed. Because DH onset timing varies,
      some patients have highly acute presentation, and most readmitted patients
      develop symptoms before reaching their sodium nadir, close symptom monitoring may
      be a reasonable alternative to routine screening.

PMID- 28449054
TI  - I Learn, Therefore I am: A Phenomenological Analysis of Meanings of Lifelong
      Learning for Vulnerable Older Adults.
AB  - Background and Objectives: This study explores the lifelong learning experience
      of vulnerable older adults to find out (a) what is involved in their activities,
      (b) what meanings they take from their learning, and (c) how participation in a
      learning program helps to maintain their well-being and independent living
      despite their daily challenges. Research Design and Methods: This study employed
      a hermeneutic phenomenological approach. As part of a larger study, we conducted
      semi-structured interviews with older learners enrolled in general interest
      courses at a public continuing education program. In this study, we particularly
      focused on 10 vulnerable participants (8 women and 2 men, aged from 70 to 90),
      and analyzed their accounts following van Manen's (2014) guided existential
      inquiry method. After the inductive thematic analysis, we clustered the
      overarching themes into five existentials (lived-body, lived-relation, lived
      space, lived-time, and lived-material) to explicate the meanings of their lived
      experience of learning. Results: The meanings of learning found in the five
      existential aspects included: (a) assurance for the dissonant body and mind; (b)
      a circle of camaraderie; (c) a balance between physical and mental spaces; (d)
      integration of past, present, and future; and (e) beyond knowledge and skills.
      Participants' continuous practice of learning works as a therapeutic self-help
      mechanism to counterbalance changes in their lifeworlds. Discussion and
      Implications: The findings contribute to the growing body of evidence of the
      wider benefits of lifelong learning and its crucial role in well-being and health
      among aging populations. Governments at all levels should take full advantage of
      these benefits.

PMID- 28449053
TI  - Fresh fruit consumption and all-cause and cause-specific mortality: findings from
      the China Kadoorie Biobank.
AB  - Background: Higher fruit consumption is associated with lower risk of
      cardiovascular disease (CVD). Substantial uncertainties remain, however, about
      the associations of fruit consumption with all-cause mortality and mortality from
      subtypes of CVD and major non-vascular diseases, especially in China. Methods: In
      2004-08, the nationwide China Kadoorie Biobank Study recruited > 0.5 million
      adults aged 30-79 years from 10 diverse localities in China. Fresh fruit
      consumption was estimated using an interviewer-administered electronic
      questionnaire, and mortality data were collected from death registries. Among the
      462 342 participants who were free of major chronic diseases at baseline, 17 894
      deaths were recorded during ~ 7 years of follow-up. Cox regression yielded
      adjusted rate ratios (RRs) for all-cause and cause-specific mortality associated
      with fruit consumption. Results: At baseline, 28% of participants reported
      consuming fruit >= 4 days/week (regular consumers) and 6% reported never/rarely
      consuming fruit (non-consumers). Compared with non-consumers, regular consumers
      had 27% [RR = 0.73, 95% confidence interval (CI) 0.70-0.76] lower all-cause
      mortality, 34% lower CVD mortality (n = 6166; RR = 0.66, 0.61-0.71), 17% lower
      cancer mortality (n = 6796; RR = 0.83, 0.78-0.89) and 42% lower mortality from
      chronic obstructive pulmonary disease (COPD) (n = 1119; RR = 0.58, 0.47-0.71).
      For each of the above, there was an approximately log-linear dose-response
      relationship with amount consumed. For mortality from site-specific cancers,
      fruit consumption was inversely associated with digestive tract cancer (n = 2265;
      RR = 0.72, 0.64-0.81), particularly oesophageal cancer (n = 801; RR = 0.65, 0.50
      0.83), but not with cancer of lung or liver. Conclusions: Among Chinese adults,
      higher fresh fruit consumption was associated with significantly lower mortality
      from several major vascular and non-vascular diseases. Given the current low
      population level of fruit consumption, substantial health benefits could be
      gained from increased fruit consumption in China.

PMID- 28449055
TI  - Primary tumor sidedness has an impact on prognosis and treatment outcome in
      metastatic colorectal cancer: results from two randomized first-line panitumumab
      studies.
AB  - Background: Previous studies have reported the prognostic impact of primary tumor
      sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab
      efficacy. The present retrospective analysis of two panitumumab trials
      investigated a possible association between tumor sidedness and treatment
      efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors.
      Materials and methods: Data from two randomized first-line panitumumab trials
      were analyzed for treatment outcomes by primary tumor sidedness for RAS WT
      patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus
      FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus
      bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon
      were coded as right-sided, while tumors located from the splenic flexure to
      rectum were considered left-sided. Results: Tumor sidedness ascertainment (RAS WT
      population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and
      22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse
      for all efficacy parameters compared with patients with left-sided disease in the
      RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left
      sided tumors, panitumumab provided better outcomes than the comparator treatment,
      including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted
      hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard
      ratio = 0.77, P = 0.3125). Conclusion: The results of these retrospective
      analyses confirm that in RAS WT patients, right-sided primary tumors are
      associated with worse prognosis than left-sided tumors, regardless of first-line
      treatment received. RAS WT patients with left-sided tumors derive greater benefit
      from panitumumab-containing treatment than chemotherapy alone or combined with
      bevacizumab, including an overall survival advantage (treatment difference: PRIME
      6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment
      could be drawn for RAS WT patients with right-sided mCRC due to the relatively
      low number of paxtients. Further research in this field is warranted. Trial
      registration (Clinicaltrials.gov): PRIME (NCT00364013), PEAK (NCT00819780).

PMID- 28449056
TI  - Plant Hexokinases are Multifaceted Proteins.
AB  - Sugars are the main carbon and energy source in cells, but they can also act as
      signaling molecules that affect the whole plant life cycle. Certain tissues can
      produce sugars and supply them to others, and this plant tissue heterogeneity
      makes sugar signaling a highly complex process that requires elements capable of
      perceiving changes in sugar concentrations among different tissues, cell
      compartments and developmental stages. In plants, the regulatory effects of
      glucose (Glc) have been the most studied to date. The first Glc sensor identified
      in plants was hexokinase (HXK), which is currently recognized as a dual-function
      protein. In addition to its catalytic activity, this enzyme can also repress the
      expression of some photosynthetic genes in response to high internal Glc
      concentrations. Additionally, the catalytic activity of HXKs has a profound
      impact on cell metabolism and other sugar signaling pathways that depend on
      phosphorylated hexoses and intermediate glycolytic products. HXKs are the only
      proteins that are able to phosphorylate Glc in plants, since no evidence has been
      provided to date concerning the existence of a glucokinase. Moreover, the
      intracellular localization of HXKs seems to be crucial to their activity and
      sensor functions. Recently, two new and surprising functions have been described
      for HXKs. In this review, we discuss the versatility of HXKs in regard to their
      catalytic and glucose sensor activities, intracellular location, protein-protein
      and hormone interactions, as well as how these HXK characteristics influence
      plant growth and development, in an effort to understand this enzyme's role in
      improving plant productivity.

PMID- 28449058
TI  - Corrigendum to: Diagnosis and management of acute deep vein thrombosis: a joint
      consensus document from the european society of cardiology working groups of
      aorta and peripheral circulation and pulmonary circulation and right ventricular
      function.

PMID- 28449057
TI  - The Streptomyces master regulator BldD binds c-di-GMP sequentially to create a
      functional BldD2-(c-di-GMP)4 complex.
AB  - Streptomyces are ubiquitous soil bacteria that undergo a complex developmental
      transition coinciding with their production of antibiotics. This transition is
      controlled by binding of a novel tetrameric form of the second messenger, 3?-5?
      cyclic diguanylic acid (c-di-GMP) to the master repressor, BldD. In all domains
      of life, nucleotide-based second messengers allow a rapid integration of external
      and internal signals into regulatory pathways that control cellular responses to
      changing conditions. c-di-GMP can assume alternative oligomeric states to effect
      different functions, binding to effector proteins as monomers, intercalated
      dimers or, uniquely in the case of BldD, as a tetramer. However, at physiological
      concentrations c-di-GMP is a monomer and little is known about how higher
      oligomeric complexes assemble on effector proteins and if intermediates in
      assembly pathways have regulatory significance. Here, we show that c-di-GMP binds
      BldD using an ordered, sequential mechanism and that BldD function necessitates
      the assembly of the BldD2-(c-di-GMP)4 complex.

PMID- 28449059
TI  - Marijuana Use Impacts Midlife Cardiovascular Events in HIV-Infected Men.
AB  - Background: Marijuana use is prevalent among persons infected with human
      immunodeficiency virus (HIV), but its long-term effects on HIV disease
      progression and comorbidities are unknown. Methods: In this prospective study of
      558 HIV-infected men enrolled in the Multicenter AIDS Cohort Study between 1990
      and 2010, there were 182 HIV seroconverters and 376 with viral suppression on
      combination antiretroviral therapy (ART). Associations between heavy marijuana
      use and HIV disease markers or white blood cell (WBC) count were examined using
      mixed-effects and linear regression models. Effects of marijuana use on
      cardiovascular (CV) events and other endpoints were estimated using Kaplan-Meier
      and logistic regression analyses. Results: The median baseline age of
      participants was 41, 66% were white, 79% had education >12 years, and 20%
      reported heavy marijuana use at >=50% of biannual visits during follow-up. Long
      term heavy marijuana use showed no significant associations with viral load, CD4
      counts, AIDS, cancer, or mortality in both cohorts but was independently
      associated with increased CV events between ages 40-60 after adjusting for age,
      tobacco smoking, viral load, and traditional risk factors (odds ratio [OR], 2.5;
      95% confidence interval [CI] 1.3, 5.1). Marijuana and tobacco use were each
      independently associated with higher WBC counts in adjusted models (P < .01); the
      highest quartile of WBC counts (>=6500 cells/uL) was associated with increased CV
      events (OR 4.3; 95% CI, 1.5, 12.9). Conclusions: Heavy marijuana use is a risk
      factor for CV disease in HIV-infected men ages 40-60, independent of tobacco
      smoking and traditional risk factors.

PMID- 28449060
TI  - The influence of miniscrew insertion torque.
AB  - Objective: The aim of this in vitro study was to evaluate the progressive
      development of surface microdamage produced following the insertion of
      orthodontic miniscrews (OMs) into 1.5 mm thick porcine tibia bone using maximum
      insertion torque values of 12 Ncm, 18 Ncm, and 24 Ncm. Methods: Aarhus OMs
      (diameter 1.5 mm; length 6 mm) were inserted into 1.5 mm porcine bone using a
      torque limiting hand screwdriver set at 12 Ncm, 18 Ncm, and 24 Ncm. A custom rig
      equipped with a compression load cell was used to record the compression force
      exerted during manual insertion. A sequential staining technique was used to
      identify microdamage viewed under laser confocal microscopy. Virtual slices were
      created and stitched together to form a compressed two-dimensional composition of
      the microdamage. Histomorphometric parameters, including total damage area,
      diffuse damage area, maximum crack length, maximum damage radius, and maximum
      diffuse damage radius, were measured. Kruskal-Wallis Tests and Wilcoxon Rank-Sum
      Tests were used to analyse the generated data. Results: All OMs inserted using 12
      Ncm failed to insert completely, while partial insertion was observed for two OMs
      inserted at 18 Ncm. Complete insertion was achieved for all OMs inserted at 24
      Ncm. Histomorphometrically, OMs inserted using 24 Ncm produced a significantly
      larger diffuse damage area (P < 0.05; P < 0.05) and maximum diffuse damage radius
      (P < 0.05; P < 0.05), for both the entry and exit surfaces, respectively,
      compared with the 12 Ncm and 18 Ncm groups. Conclusions: Insertion torque can
      influence the degree of OM insertion and, subsequently, the amount of microdamage
      formed following insertion into 1.5 mm thick porcine tibia bone. An increase in
      insertion torque corresponds with greater insertion depth and larger amounts of
      microdamage.

PMID- 28449061
TI  - Cohort Profile: The 1895, 1905, 1910 and 1915 Danish Birth Cohort Studies -
      secular trends in the health and functioning of the very old.

PMID- 28449062
TI  - Calculating the quality of public high-throughput sequencing data to obtain a
      suitable subset for reanalysis from the Sequence Read Archive.
AB  - It is important for public data repositories to promote the reuse of archived
      data. In the growing field of omics science, however, the increasing number of
      submissions of high-throughput sequencing (HTSeq) data to public repositories
      prevents users from choosing a suitable data set from among the large number of
      search results. Repository users need to be able to set a threshold to reduce the
      number of results to obtain a suitable subset of high-quality data for
      reanalysis. We calculated the quality of sequencing data archived in a public
      data repository, the Sequence Read Archive (SRA), by using the quality control
      software FastQC. We obtained quality values for 1 171 313 experiments, which can
      be used to evaluate the suitability of data for reuse. We also visualized the
      data distribution in SRA by integrating the quality information and metadata of
      experiments and samples. We provide quality information of all of the archived
      sequencing data, which enable users to obtain sufficient quality sequencing data
      for reanalyses. The calculated quality data are available to the public in
      various formats. Our data also provide an example of enhancing the reuse of
      public data by adding metadata to published research data by a third party.

PMID- 28449063
TI  - Extraction and Determination of Quercetin from Ginkgo biloba by DESs-Based
      Polymer Monolithic Cartridge.
AB  - Deep eutectic solvents (DES) were formed from choline chloride (ChCl). DES
      modified polymer monolithic (DES-M), template molecular polymer monolithic and
      non-DES-M without a molecular template were synthesized in identical process.
      These polymer materials were characterized by field emission scanning electron
      microscopy and Fourier transform infrared spectroscopy. The significant selective
      adsorption properties of the polymers were assessed by an absorption capacity
      experiment and solid-phase extraction (SPE). The optimized extraction procedure
      was as follows: ultrasonic time (30 min), optimal solvent (ethanol) and liquid to
      material ratio (20 mL g-1). Under this condition, the amount of quercetin
      extracted from Ginkgo biloba was 290.8 mg g-1. The purification of G. biloba was
      achieved by the SPE process. Based on the results, DESs-based monolithic
      cartridges can be used for simple and efficient extraction and as a pre
      concentration technique for the purification of bioactive compounds or drugs in
      aqueous environments with high affinity and selectivity.

PMID- 28449064
TI  - Using the Modified Magee Equation to Identify Patients Unlikely to Benefit From
      the 21-Gene Recurrence Score Assay (Oncotype DX Assay).
AB  - Objectives: This study aimed to compare a modified Magee equation with Oncotype
      DX (Genomic Health, Redwood City, CA) recurrence score (RS) and identify patients
      who are unlikely to benefit from Oncotype DX. Methods: Magee equation RS was
      calculated in 438 cases and correlated with Oncotype DX RS. Results: The Pearson
      correlation coefficient ( r ) for the Magee equation and Oncotype DX RS was
      0.6645 ( P  < .00001), and the overall agreement was 66.4%. All cases (11.6%)
      with a Magee equation RS greater than 30 or 11 or less had been correctly
      predicted to have either high Oncotype DX RS or low Oncotype DX RS, respectively.
      Conclusions: The modified Magee equation is able to identify up to 12% patients
      who are unlikely to benefit from Oncotype DX testing. Using the modified Magee
      equation RS on these patients would be an alternative to Oncotype DX, leading to
      cost savings.

PMID- 28449066
TI  - Childhood Maltreatment and Psychological Well-Being in Later Life: The Mediating
      Effect of Contemporary Relationships with the Abusive Parent.
AB  - Objectives: Parental childhood maltreatment has a negative impact on
      psychological well-being in adulthood. However, little is known about whether and
      how contemporary relationships with an abusive parent might explain the long-term
      harmful effects. Thus, this study aims to examine the mediating effect of later
      life relationships with an abusive parent on the association between parental
      childhood maltreatment and psychological well-being. Methods: Using the 2004-2005
      Wisconsin Longitudinal Study, this study analyzed a total of 1,696 adults aged 65
      years. A series of ordinary least squares regression and mediational analyses
      were performed. Results: Key findings showed that maternal childhood neglect and
      abuse were associated with decreased emotional closeness with mothers, which was,
      in turn, associated with diminished psychological well-being. In addition,
      childhood neglect was associated with less frequent exchanges of social support
      with mothers, which was, in turn, associated with diminished psychological well
      being. Discussion: This study suggests that, despite childhood maltreatment,
      parent-child relationships persist throughout life, and the continuing
      relationship with an abusive parent may undermine adult victims' psychological
      well-being. When intervening with mental health issues of adults who have
      experienced childhood maltreatment, their unresolved issues with the parent
      should be properly addressed.

PMID- 28449065
TI  - A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone,
      causes Perrault syndrome.
AB  - Perrault syndrome (PS) is a rare recessive disorder characterized by ovarian
      dysgenesis and sensorineural deafness. It is clinically and genetically
      heterogeneous, and previously mutations have been described in different genes,
      mostly related to mitochondrial proteostasis. We diagnosed three unrelated
      females with PS and set out to identify the underlying genetic cause using exome
      sequencing. We excluded mutations in the known PS genes, but identified a single
      homozygous mutation in the ERAL1 gene (c.707A > T; p.Asn236Ile). Since ERAL1
      protein binds to the mitochondrial 12S rRNA and is involved in the assembly of
      the small mitochondrial ribosomal subunit, the identified variant represented a
      likely candidate. In silico analysis of a 3D model for ERAL1 suggested that the
      mutated residue hinders protein-substrate interactions, potentially affecting its
      function. On a molecular basis, PS skin fibroblasts had reduced ERAL1 protein
      levels. Complexome profiling of the cells showed an overall decrease in the
      levels of assembled small ribosomal subunit, indicating that the ERAL1 variant
      affects mitochondrial ribosome assembly. Moreover, levels of the 12S rRNA were
      reduced in the patients, and were rescued by lentiviral expression of wild type
      ERAL1. At the physiological level, mitochondrial respiration was markedly
      decreased in PS fibroblasts, confirming disturbed mitochondrial function.
      Finally, knockdown of the C. elegans ERAL1 homologue E02H1.2 almost completely
      blocked egg production in worms, mimicking the compromised fertility in PS
      affected women. Our cross-species data in patient cells and worms support the
      hypothesis that mutations in ERAL1 can cause PS and are associated with changes
      in mitochondrial metabolism.

PMID- 28449067
TI  - Using high-throughput barcode sequencing to efficiently map connectomes.
AB  - The function of a neural circuit is determined by the details of its synaptic
      connections. At present, the only available method for determining a neural
      wiring diagram with single synapse precision-a 'connectome'-is based on imaging
      methods that are slow, labor-intensive and expensive. Here, we present SYNseq, a
      method for converting the connectome into a form that can exploit the speed and
      low cost of modern high-throughput DNA sequencing. In SYNseq, each neuron is
      labeled with a unique random nucleotide sequence-an RNA 'barcode'-which is
      targeted to the synapse using engineered proteins. Barcodes in pre- and
      postsynaptic neurons are then associated through protein-protein crosslinking
      across the synapse, extracted from the tissue, and joined into a form suitable
      for sequencing. Although our failure to develop an efficient barcode joining
      scheme precludes the widespread application of this approach, we expect that with
      further development SYNseq will enable tracing of complex circuits at high speed
      and low cost.

PMID- 28449069
TI  - Erratum.

PMID- 28449068
TI  - Development of a novel human recellularized endometrium that responds to a 28-day
      hormone treatment.
AB  - Three-dimensional (3D) in vitro models have been established to study the
      physiology and pathophysiology of the endometrium. With emerging evidence that
      the native extracellular matrix (ECM) provides appropriate cues and growth
      factors essential for tissue homeostasis, we describe, a novel 3D endometrium in
      vitro model developed from decellularized human endometrial tissue repopulated
      with primary endometrial cells. Analysis of the decellularized endometrium using
      mass spectrometry revealed an enrichment of cell adhesion molecules, cytoskeletal
      proteins, and ECM proteins such as collagen IV and laminin. Primary endometrial
      cells within the recellularized scaffolds proliferated and remained viable for an
      extended period of time in vitro. In order to evaluate the hormonal response of
      cells within the scaffolds, the recellularized scaffolds were treated with a
      modified 28-day hormone regimen to mimic the human menstrual cycle. At the end of
      28 days, the cells within the endometrial scaffold expressed both estrogen and
      progesterone receptors. In addition, decidualization markers, IGFBP-1 and
      prolactin, were secreted upon addition of dibutyryl cyclic AMP indicative of a
      decidualization response. This 3D model of the endometrium provides a new
      experimental tool to study endometrial biology and drug testing.

PMID- 28449070
TI  - In situ screening for postsynaptic cell adhesion molecules during synapse
      formation.
AB  - Neuronal synapse formation is regulated by pre- and postsynaptic cell adhesion
      molecules. Presynaptic neurexins (NRXNs) and receptor protein tyrosine
      phosphatases (RPTPs; PTPdelta, PTPsigma and LAR in mammals) can induce
      postsynaptic differentiation through the interaction with various postsynaptic
      cell adhesion molecules. Here, we developed a novel in situ screening method to
      identify postsynaptic membranous proteins involved in synaptogenesis. Magnetic
      beads coated with the extracellular domains of NRXN1beta(-S4) and PTPdelta-A6
      variants preferentially induced excitatory postsynaptic differentiation on the
      beads' surface when co-cultured with cortical neurons. After inducing
      postsynaptic sites on these beads, protein complexes including NRXN1beta(
      S4)/PTPdelta-A6 and their ligands on the neuronal membrane were chemically cross
      linked and purified using a magnetic separator. Liquid chromatography-tandem mass
      spectrometry analysis of the complexes revealed two types of postsynaptic ligands
      for NRXN1beta(-S4) and PTPdelta-A6, one has an activity to induce presynaptic
      differentiation in a trans manner, whereas the other has no such activity. These
      results suggest that synapse formation is regulated by the interplay between
      presynaptic NRXN/PTPdelta and their postsynaptic ligands with functionally
      different impacts on pre- and postsynaptic differentiation. Thus, our in situ
      screening method for identifying synapse-organizing complexes will help to
      understand the molecular basis for elaborate neuronal networks.

PMID- 28449071
TI  - Letter: Commentary: Deep Brain Stimulation as Clinical Innovation: An Ethical and
      Organizational Framework to Sustain Deliberations about Psychiatric Deep Brain
      Stimulation.

PMID- 28449073
TI  - Genetics of phenotypic plasticity and biomass traits in hybrid willows across
      contrasting environments and years.
AB  - Background and Aims: Phenotypic plasticity can affect the geographical
      distribution of taxa and greatly impact the productivity of crops across
      contrasting and variable environments. The main objectives of this study were to
      identify genotype-phenotype associations in key biomass and phenology traits and
      the strength of phenotypic plasticity of these traits in a short-rotation coppice
      willow population across multiple years and contrasting environments to
      facilitate marker-assisted selection for these traits. Methods: A hybrid Salix
      viminalis  * ( S. viminalis * Salix schwerinii ) population with 463 individuals
      was clonally propagated and planted in three common garden experiments comprising
      one climatic contrast between Sweden and Italy and one water availability
      contrast in Italy. Several key phenotypic traits were measured and phenotypic
      plasticity was estimated as the trait value difference between experiments.
      Quantitative trait locus (QTL) mapping analyses were conducted using a dense
      linkage map and phenotypic effects of S. schwerinii haplotypes derived from
      detected QTL were assessed. Key Results: Across the climatic contrast, clone
      predictor correlations for biomass traits were low and few common biomass QTL
      were detected. This indicates that the genetic regulation of biomass traits was
      sensitive to environmental variation. Biomass QTL were, however, frequently
      shared across years and across the water availability contrast. Phenology QTL
      were generally shared between all experiments. Substantial phenotypic plasticity
      was found among the hybrid offspring, that to a large extent had a genetic
      origin. Individuals carrying influential S. schwerinii haplotypes generally
      performed well in Sweden but less well in Italy in terms of biomass production.
      Conclusions: The results indicate that specific genetic elements of S. schwerinii
      are more suited to Swedish conditions than to those of Italy. Therefore,
      selection should preferably be conducted separately for such environments in
      order to maximize biomass production in admixed S. viminalis * S. schwerinii
      populations.

PMID- 28449072
TI  - Functions of galectins as 'self/non-self'-recognition and effector factors.
AB  - Carbohydrate structures on the cell surface encode complex information that
      through specific recognition by carbohydrate-binding proteins (lectins) modulates
      interactions between cells, cells and the extracellular matrix, or mediates
      recognition of potential microbial pathogens. Galectins are a family of beta
      galactoside-binding lectins, which are evolutionary conserved and have been
      identified in most organisms, from fungi to invertebrates and vertebrates,
      including mammals. Since their discovery in the 1970s, their biological roles,
      initially understood as limited to recognition of endogenous carbohydrate ligands
      in embryogenesis and development, have expanded in recent years by the discovery
      of their roles in tissue repair and regulation of immune homeostasis. More
      recently, evidence has accumulated to support the notion that galectins can also
      bind glycans on the surface of potentially pathogenic microbes, and function as
      recognition and effector factors in innate immunity, thus establishing a new
      paradigm. Furthermore, some parasites 'subvert' the recognition roles of the
      vector/host galectins for successful attachment or invasion. These recent
      findings have revealed a striking functional diversification in this structurally
      conserved lectin family.

PMID- 28449074
TI  - FireProt: web server for automated design of thermostable proteins.
AB  - There is a continuous interest in increasing proteins stability to enhance their
      usability in numerous biomedical and biotechnological applications. A number of
      in silico tools for the prediction of the effect of mutations on protein
      stability have been developed recently. However, only single-point mutations with
      a small effect on protein stability are typically predicted with the existing
      tools and have to be followed by laborious protein expression, purification, and
      characterization. Here, we present FireProt, a web server for the automated
      design of multiple-point thermostable mutant proteins that combines structural
      and evolutionary information in its calculation core. FireProt utilizes sixteen
      tools and three protein engineering strategies for making reliable protein
      designs. The server is complemented with interactive, easy-to-use interface that
      allows users to directly analyze and optionally modify designed thermostable
      mutants. FireProt is freely available at http://loschmidt.chemi.muni.cz/fireprot.

PMID- 28449075
TI  - New viral outbreaks: time for rheumatologists to get involved?: Chronic
      arthralgias and viral infections.

PMID- 28449076
TI  - QTL analysis of the developmental response to L-glutamate in Arabidopsis roots
      and its genotype-by-environment interactions.
AB  - Primary root growth in Arabidopsis and a number of other species has previously
      been shown to be remarkably sensitive to the presence of external glutamate, with
      glutamate signalling eliciting major changes in root architecture. Using two
      recombinant inbred lines from reciprocal crosses between Arabidopsis accessions
      C24 and Col-0, we have identified one large-effect quantitative trait locus
      (QTL), GluS1, and two minor QTLs, GluS2 and GluS3, which together accounted for
      41% of the phenotypic variance in glutamate sensitivity. The presence of the
      GluS1 locus on chromosome 3 was confirmed using a set of C24/Col-0 isogenic
      lines. GluS1 was mapped to an interval between genes At3g44830-At3g46880. When
      QTL mapping was repeated under a range of environmental conditions, including
      temperature, shading and nitrate supply, a strong genotype-by-environment
      interaction in the controls for the glutamate response was identified. Major
      differences in the loci controlling this trait were found under different
      environmental conditions. Here we present evidence for the existence of loci on
      chromosomes 1 and 5 epistatically controlling the response of the GluS1 locus to
      variations in ambient temperature, between 20 degrees C and 26 degrees C. In
      addition, a locus on the long arm of chromosome 1 was found to play a major role
      in controlling the ability of external nitrate signals to antagonize the
      glutamate effect. We conclude that there are multiple loci controlling natural
      variation in glutamate sensitivity in Arabidopsis roots and that epistatic
      interactions play an important role in modulating glutamate sensitivity in
      response to changes in environmental conditions.

PMID- 28449078
TI  - Surface electrocardiography characteristics and radiofrequency catheter ablation
      of idiopathic ventricular arrhythmias originating from the left infero-septal
      papillary muscles: differences from those originating from the left posterior
      fascicle.
AB  - Aims: Distinguishing between ventricular arrhythmias originating from the left
      ventricular infero-septal papillary muscles (PM) and those from the left
      posterior fascicle (LPF) by surface electrocardiography (ECG) is very difficult.
      This study aimed to report the ECG characteristics and radiofrequency catheter
      ablation of PM and LPF ventricular arrhythmias. Methods and results: A total of
      127 patients underwent catheter ablation of idiopathic ventricular arrhythmias
      originating from the LPF (n = 106; 85 males; 10-70 years) or PM (n = 21; 14
      males; 4-68 years) were studied. A three-dimensional electroanatomic system (3D
      EAS) was used to aid ablation. PM ventricular arrhythmias had a longer QRS
      duration (154.4 +/- 18.0 vs. 119.7 +/- 12.6 ms, P < 0.001) than LPF ventricular
      arrhythmias. All 7 ventricular arrhythmias with QRS duration >160 ms originated
      from the PM, whereas all 87 ventricular arrhythmias with QRS duration <130 ms
      arose from the LPF. In 33 ventricular arrhythmias with QRS 130-160 ms, all 13
      with Vi/Vt <= 0.85 originated from the PM, and 19 of 20 with Vi/Vt > 0.85 arose
      from the LPF. Of the 8 PM ventricular arrhythmias patients whose initial ablation
      was undertaken using a non-irrigated 4 mm-tip catheter, 1 failed and 6 recurred.
      However, of the remaining 13 ones using an irrigated catheter and the 3D-EAS, all
      succeeded and 2 recurred. No complications were noted in any patient. Conclusion:
      PM ventricular arrhythmias could be identified from LPF ventricular arrhythmias
      by calculation of QRS duration combined with Vi/Vt using ECG.

PMID- 28449077
TI  - Executive Network Activation is Linked to Walking Speed in Older Adults:
      Functional MRI and TCD Ultrasound Evidence From the MOBILIZE Boston Study.
AB  - Background: Changes in cerebral blood flow velocity (CBF) in response to a
      cognitive task (task-related DeltaCBF) have been shown by Transcranial Doppler
      ultrasonography (TCD) to be reduced in slow walkers. However, it is unknown
      whether reduced task-related DeltaCBF is associated with reduced neural activity
      in specific brain regions, as measured by blood-oxygen-level dependent (BOLD)
      functional magnetic resonance imaging (fMRI). Methods: We assessed the regional
      changes in neural activity associated with reduced middle cerebral artery (MCA)
      task-related DeltaCBF to an executive task and slow walking speed in 67 community
      dwelling older adults from the MOBILIZE Boston Study. Participants underwent
      walking assessments and TCD ultrasonography measures of MCA DeltaCBF during the n
      back task of executive function. A subset of participants (n = 27) completed the
      same task during fMRI. Individual BOLD activation maps for the n-back task were
      correlated with TCD measures and network-level averages were associated with TCD
      and preferred walking speed. Results: Participants with diminished task-related
      DeltaCBF walked more slowly (beta = .39, p = .001). fMRI revealed significant
      associations between task-related DeltaCBF and regional BOLD activation in
      several brain regions/networks supplied by the MCA. Of these regions and
      networks, those within the executive network were most strongly associated with
      walking speed (beta = .36, p = .01). Conclusions: Task-related DeltaCBF during an
      executive function task is related to activation in several neural networks and
      impairment in the ability to recruit the executive network in particular is
      associated with slow walking speed in older adults.

PMID- 28449080
TI  - For Their Financial Benefit: Determination of Financial Capability for Adult
      Beneficiaries of Social Security Disability.

PMID- 28449079
TI  - Small non-coding RNA and cancer.
AB  - The ENCODE project has reported that at least 80% of the human genome is
      biologically active, yet only a small part of human DNA encodes for protein. The
      massive amount of RNA transcribed but not translated into protein can be
      classified as housekeeping RNA (such as rRNA, tRNA) and regulatory RNA (such as
      miRNA, piRNA, lncRNA). Small non-coding RNAs, in particular, have been the focus
      of many studies in the last 20 years and their fundamental role in many human
      diseases is currently well established. Inter alia, their role in cancer
      development and progression, as well as in drug resistance, is being increasingly
      investigated. In this review, focusing our attention on recent research results,
      we provide an overview of the four large classes of small non-coding RNAs,
      namely, miRNAs, piRNAs, snoRNA and the new class of tRNA-derived fragments,
      highlighting their fundamental role in cancer and their potential as diagnostic
      and prognostic biomarkers.

PMID- 28449081
TI  - The Coxiella Burnetii type IVB secretion system (T4BSS) component DotA is
      released/secreted during infection of host cells and during in vitro growth in a
      T4BSS-dependent manner.
AB  - Coxiella burnetii is a Gram-negative intracellular pathogen and is the causative
      agent of the zoonotic disease Q fever. To cause disease, C. burnetii requires a
      functional type IVB secretion system (T4BSS) to transfer effector proteins
      required for the establishment and maintenance of a membrane-bound
      parasitophorous vacuole (PV) and further modulation of host cell process.
      However, it is not clear how the T4BSS interacts with the PV membrane since
      neither a secretion pilus nor an extracellular pore forming apparatus has not
      been described. To address this, we used the acidified citrate cysteine medium
      (ACCM) along with cell culture infection and immunological techniques to identify
      the cellular and extracellular localization of T4BSS components. Interestingly,
      we found that DotA and IcmX were secreted/released in a T4BSS-dependent manner
      into the ACCM. Analysis of C. burnetii-infected cell lines revealed that DotA
      colocalized with the host cell marker CD63 (LAMP3) at the PV membrane. In the
      absence of bacterial protein synthesis, DotA also became depleted from the PV
      membrane. These data are the first to identify the release/secretion of C.
      burnetii T4BSS components during axenic growth and the interaction of a T4BSS
      component with the PV membrane during infection of host cells.

PMID- 28449083
TI  - Proteomic response to linoleic acid hydroperoxide in Saccharomyces cerevisiae.
AB  - Yeast AP-1 transcription factor (Yap1p) and the enigmatic oxidoreductases Oye2p
      and Oye3p are involved in counteracting lipid oxidants and their unsaturated
      breakdown products. In order to uncover the response to linoleic acid
      hydroperoxide (LoaOOH) and the roles of Oye2p, Oye3p and Yap1p, we carried out
      proteomic analysis of the homozygous deletion mutants oye3Delta, oye2Delta and
      yap1Delta alongside the diploid parent strain BY4743. The findings demonstrate
      that deletion of YAP1 narrowed the response to LoaOOH, as the number of proteins
      differentially expressed in yap1Delta was 70% of that observed in BY4743. The
      role of Yap1p in regulating the major yeast peroxiredoxin Tsa1p was demonstrated
      by the decreased expression of Tsa1p in yap1Delta. The levels of Ahp1p and
      Hsp31p, previously shown to be regulated by Yap1p, were increased in LoaOOH
      treated yap1Delta, indicating their expression is also regulated by another
      transcription factor(s). Relative to BY4743, protein expression differed in
      oye3Delta and oye2Delta under LoaOOH, underscored by superoxide dismutase
      (Sod1p), multiple heat shock proteins (Hsp60p, Ssa1p, and Sse1p), the flavodoxin
      like protein Pst2p and the actin stabiliser tropomyosin (Tpm1p). Proteins
      associated with glycolysis were increased in all strains following treatment with
      LoaOOH. Together, the dataset reveals, for the first time, the yeast proteomic
      response to LoaOOH, highlighting the significance of carbohydrate metabolism, as
      well as distinction between the roles of Oye3p, Oye2p and Yap1p.

PMID- 28449082
TI  - Oral health and mortality in the Golestan Cohort Study.
AB  - Background: Previous studies have found associations between oral health and
      mortality, but the majority of previous studies have been conducted in high
      income countries. Methods: We used data from the Golestan Cohort Study, a study
      of 50 045 people aged 40 to 75 years in north eastern Iran, recruited from
      January 2004 to June 2008. Tooth loss and decayed, missing and filled teeth
      (DMFT) were assessed by trained physicians. Frequency of tooth brushing and use
      of dentures were self-reported. Cause-specific mortality was ascertained through
      March 2014. We calculated hazard ratios (HRs) and 95% confidence intervals (95%
      CIs) for the associations between the oral health variables, overall mortality
      and cause-specific mortality. Results: Participants with the greatest tooth loss
      had increased overall mortality (HR 1.43; 95% CI: 1.28, 1.61) compared with those
      with the least tooth loss; similar estimates were observed for DMFT score. For
      cause-specific mortality, an increased risk of death was found for tooth loss and
      mortality from cardiovascular disease (HR 1.33; 95% CI: 1.13, 1.56), cancer (HR
      1.30; 95% CI: 1.03, 1.65) and injuries (HR 1.99; 95% CI: 1.28, 3.09). The
      associations between oral health and injury mortality were strongly attenuated
      after exclusion of participants with comorbid conditions at baseline. No
      statistical interaction was found between denture use and tooth loss or DMFT on
      mortality. Conclusions: Poor oral health appears to predict overall and cause
      specific mortality in populations in economic transition. Investigation of the
      underlying mechanisms might provide an important contribution to reducing
      mortality.

PMID- 28449084
TI  - Perceived Quality of Life following Elder Mistreatment in Rural India.
AB  - Objectives: Using resilience theory, we examined multiple risks (individual,
      familial, and mistreatment characteristics) and promotive factors (mastery and
      social support) associated with perceived quality of life following mistreatment
      and tested two competing models, compensatory and protective models, to explain
      the role of promotive factors in the mistreatment-wellbeing linkage. Method: Face
      to-face interviews were conducted by administering standardized instruments to
      897 randomly selected older adults in rural Tamil Nadu, India. Information from
      187 older adults, who, in the interview had reported mistreatment in the past 1
      year formed the analysis. Quality of life following mistreatment was measured
      using the Satisfaction with Life Scale. Mistreatment was measured by an adapted
      version of the Conflict Tactics Scale. Results: Being single, hailing from a low
      income family, experiencing high levels of relationship strain, and experiencing
      more than one type of mistreatment were associated with decreased quality of
      life. High levels of mastery and social support were associated with high levels
      of quality of life following mistreatment. There was support for both
      compensatory and protective-reactive models of resilience. Some of the resources
      that counteract the negative effects of adversities and mistreatment appear to be
      effective only at lower levels of mistreatment. Discussion: Quality of life
      following mistreatment was influenced by multiple risk and promotive factors,
      results that are consistent with resilience theory. Concerted efforts must be
      undertaken to bolster protective factors and minimize risk factors to enhance
      quality of life following mistreatment.

PMID- 28449085
TI  - Guanine quadruplex monoclonal antibody 1H6 cross-reacts with restrained thymidine
      rich single stranded DNA.
AB  - Previously we reported the production and characterization of monoclonal antibody
      1H6 raised against (T4G4)2 intermolecular guanine quadruplex (G4) DNA structures
      (Henderson A. et al. (2014) Nucleic Acids Res., 42, 860-869; Hoffmann R.F. et al.
      (2016) Nucleic Acids Res., 44, 152-163). It was shown that 1H6 strongly stains
      nuclei and has exquisite specificity for heterochromatin by immuno-electron
      microscopy. Here we extend our studies of 1H6 reactivity using enzyme-linked
      immunosorbent assay (ELISA) and microscale thermophoresis (MST). As previously
      reported, 1H6 was found to strongly bind intermolecular G4 structures with a
      (T4G4)2 sequence motif. However, using both methods we did not detect significant
      binding to G4 structures without thymidines in their sequence motif or to G4
      structures made with (T2G4)2 oligonucleotides. In addition, we observed strong,
      sequence-specific binding of 1H6 by ELISA to immobilized single stranded poly(T)
      DNA but not to immobilized poly(C) or poly(A) homo-polymers. Cross-reactivity of
      1H6 to poly(T) was not measured in solution using MST. 1H6 was furthermore found
      to bind to selected areas on DNA fibers but only after DNA denaturation. Based on
      these observations we propose that 1H6 binds with high affinity to adjacent T's
      that are restricted in their movement in selected G4 structures and denatured
      DNA. Cross-reactivity of 1H6 to immobilized single stranded T-rich DNA next to
      its previously reported specificity for bona fide G4 structures needs to be taken
      into account in the interpretation of 1H6 binding to (sub-) cellular structures.

PMID- 28449086
TI  - A Coordinated Action of Blood-Borne and Brain Insulin-Like Growth Factor I in the
      Response to Traumatic Brain Injury.
AB  - In response to injury, the brain produces different neuroprotective molecules,
      such as insulin-like growth factor I (IGF-I). However, IGF-I is also taken up by
      the brain from the circulation in response to physiological stimuli. Herein, we
      analyzed in mice the relative contribution of circulating and locally produced
      IGF-I to increased brain IGF-I levels after insult. Traumatic brain injury (TBI)
      induced by a controlled impact resulted in increased IGF-I levels in the vicinity
      of the lesion, but mice with low serum IGF-I showed significantly lower
      increases. Indeed, in normal mice, peripheral IGF-I accumulated at the lesion
      site after injury, and at the same time serum IGF-I levels decreased.
      Collectively, these data suggest that serum IGF-I enter into the brain after TBI
      and contributes to increased brain IGF-I levels at the injury site. This
      connection between central and circulating IGF-I provides an amenable route for
      treatment, as subcutaneous administration of IGF-I to TBI mice led to functional
      recovery. These latter results add further support to the use of systemic IGF-I
      or its mimetics for treatment of brain injuries.

PMID- 28449088
TI  - Clinical manifestations of scrub typhus.
AB  - The mite-borne rickettsial zoonosis scrub typhus is widely prevalent in parts of
      Southeast and Far East Asia, and northern Australia. The disease is an acute
      febrile illness, associated with rash and often an eschar, which responds
      dramatically to treatment with antibiotics. In some cases it results in a serious
      illness leading to multiple organ involvement and death. The disease
      manifestations are thought to result from a systemic vasculitis, caused by both
      direct effects of the organisms as well as an exaggerated immune response,
      although little is understood about its pathogenesis. A wide spectrum of clinical
      manifestations, affecting nearly every organ system, have been described with
      scrub typhus. Some of these manifestations are serious and life threatening. In
      this systematic review, we summarise the typical and atypical manifestations of
      scrub typhus reported in the literature. Awareness of these unusual
      manifestations will hopefully guide clinicians towards diagnosing the condition
      early, and initiating early appropriate antibiotics and other supportive
      measures.

PMID- 28449089
TI  - Erratum.

PMID- 28449087
TI  - Methyl-CpG binding domain protein 1 regulates localization and activity of Tet1
      in a CXXC3 domain-dependent manner.
AB  - Cytosine modifications diversify and structure the genome thereby controlling
      proper development and differentiation. Here, we focus on the interplay of the 5
      methylcytosine reader Mbd1 and modifier Tet1 by analyzing their dynamic
      subcellular localization and the formation of the Tet oxidation product 5
      hydroxymethylcytosine in mammalian cells. Our results demonstrate that Mbd1
      enhances Tet1-mediated 5-methylcytosine oxidation. We show that this is due to
      enhancing the localization of Tet1, but not of Tet2 and Tet3 at heterochromatic
      DNA. We find that the recruitment of Tet1 and concomitantly its catalytic
      activity eventually leads to the displacement of Mbd1 from methylated DNA.
      Finally, we demonstrate that increased Tet1 heterochromatin localization and 5
      methylcytosine oxidation are dependent on the CXXC3 domain of Mbd1, which
      recognizes unmethylated CpG dinucleotides. The Mbd1 CXXC3 domain deletion
      isoform, which retains only binding to methylated CpGs, on the other hand, blocks
      Tet1-mediated 5-methylcytosine to 5-hydroxymethylcytosine conversion, indicating
      opposite biological effects of Mbd1 isoforms. Our study provides new insights on
      how cytosine modifications, their modifiers and readers cross-regulate
      themselves.

PMID- 28449090
TI  - Alcohol consumption, sinus tachycardia, and cardiac arrhythmias at the Munich
      Octoberfest: results from the Munich Beer Related Electrocardiogram Workup Study
      (MunichBREW).
AB  - Aims: Alcohol is a risk factor for cardiac arrhythmias. Retrospective analyses
      suggest supraventricular arrhythmias consecutive to acute alcohol consumption,
      but prospective data are limited. We intended to prospectively associate acute
      alcohol consumption with cardiac arrhythmias. Methods and results: At the 2015
      Munich Octoberfest, we enrolled 3028 voluntary participants who received a
      smartphone-based ECG and breath alcohol concentration (BAC) measurements. ECGs
      were analysed for cardiac arrhythmias (sinus tachycardia, sinus arrhythmia,
      premature atrial/ventricular complexes, atrial fibrillation/flutter) and
      respiratory sinus arrhythmia. By multivariable adjusted logistic regression we
      associated BACs with cardiac arrhythmias. Similarly, we analysed 4131
      participants of the community-based KORA S4 Study (Co-operative Health Research
      in the Region of Augsburg) and associated cardiac arrhythmias with chronic
      alcohol consumption. In our acute alcohol cohort (mean age 34.4 +/- 13.3 years,
      29% women), mean BAC was 0.85 +/- 0.54 g/kg. Cardiac arrhythmias occurred in
      30.5% (sinus tachycardia 25.9%; other arrhythmia subtypes 5.4%). Breath alcohol
      concentration was significantly associated with cardiac arrhythmias overall (odds
      ratio (OR) per 1-unit change 1.75, 95% confidence interval (CI) 1.50-2.05; P <
      0.001) and sinus tachycardia in particular (OR 1.96, 95%CI 1.66-2.31; P < 0.001).
      Respiratory sinus arrhythmia measuring autonomic tone was significantly reduced
      under the influence of alcohol. In KORA S4, chronic alcohol consumption was
      associated with sinus tachycardia (OR 1.03, 95%CI 1.01-1.06; P = 0.006).
      Conclusions: Acute alcohol consumption is associated with cardiac arrhythmias and
      sinus tachycardia in particular. This partly reflects autonomic imbalance as
      assessed by significantly reduced respiratory sinus arrhythmia. Such imbalance
      might lead to sympathetically triggered atrial fibrillation resembling the
      holiday heart syndrome. ClinicalTrials.org accession number: NCT02550340.

PMID- 28449091
TI  - GWAB: a web server for the network-based boosting of human genome-wide
      association data.
AB  - During the last decade, genome-wide association studies (GWAS) have represented a
      major approach to dissect complex human genetic diseases. Due in part to limited
      statistical power, most studies identify only small numbers of candidate genes
      that pass the conventional significance thresholds (e.g. P <= 5 * 10-8). This
      limitation can be partly overcome by increasing the sample size, but this comes
      at a higher cost. Alternatively, weak association signals can be boosted by
      incorporating independent data. Previously, we demonstrated the feasibility of
      boosting GWAS disease associations using gene networks. Here, we present a web
      server, GWAB (www.inetbio.org/gwab), for the network-based boosting of human GWAS
      data. Using GWAS summary statistics (P-values) for SNPs along with reference
      genes for a disease of interest, GWAB reprioritizes candidate disease genes by
      integrating the GWAS and network data. We found that GWAB could more effectively
      retrieve disease-associated reference genes than GWAS could alone. As an example,
      we describe GWAB-boosted candidate genes for coronary artery disease and
      supporting data in the literature. These results highlight the inherent value in
      sub-threshold GWAS associations, which are often not publicly released. GWAB
      offers a feasible general approach to boost such associations for human disease
      genetics.

PMID- 28449092
TI  - Genome-wide DNA methylomes from discrete developmental stages reveal the
      predominance of non-CpG methylation in Tribolium castaneum.
AB  - Cytosine DNA methylation is a vital epigenetic regulator of eukaryotic
      development. Whether this epigenetic modification occurs in Tribolium castaneum
      has been controversial, its distribution pattern and functions have not been
      established. Here, using bisulphite sequencing (BS-Seq), we confirmed the
      existence of DNA methylation and described the methylation profiles of the four
      life stages of T. castaneum. In the T. castaneum genome, both symmetrical CpG and
      non-CpG methylcytosines were observed. Symmetrical CpG methylation, which was
      catalysed by DNMT1 and occupied a small part in T. castaneum methylome, was
      primarily enriched in gene bodies and was positively correlated with gene
      expression levels. Asymmetrical non-CpG methylation, which was predominant in the
      methylome, was strongly concentrated in intergenic regions and introns but absent
      from exons. Gene body methylation was negatively correlated with gene expression
      levels. The distribution pattern and functions of this type of methylation were
      similar only to the methylome of Drosophila melanogaster, which further supports
      the existence of a novel methyltransferase in the two species responsible for
      this type of methylation. This first life-cycle methylome of T. castaneum reveals
      a novel and unique methylation pattern, which will contribute to the further
      understanding of the variety and functions of DNA methylation in eukaryotes.

PMID- 28449093
TI  - Opinions of lung cancer clinicians on shared decision making in early-stage non
      small-cell lung cancer.
AB  - OBJECTIVES: To investigate the opinions of lung cancer clinicians concerning
      shared decision making (SDM) in early-stage non-small-cell lung cancer patients.
      METHODS: A survey was conducted among Dutch cardiothoracic surgeons and lung
      surgeons, pulmonologists and radiation oncologists. The opinions of clinicians on
      the involvement of patients in treatment decision making was assessed using a 1-5
      Likert-type scale. Through open questions, we queried barriers to and drivers of
      SDM in clinical practice. Clinicians were asked to review 7 hypothetical cases
      and indicate which treatment strategy they would choose using a 1-7 Likert-type
      scale. RESULTS: Twenty-six percent of surgeons, 20% of pulmonologists and 12% of
      radiation oncologists indicated that they always engage in SDM (16% missing; P
      value = 0.10). Most respondents stated that, ideally, doctors and patients should
      decide together (surgeons 52%, pulmonologists 67% and radiation oncologists 35%;
      P-value = 0.005). Thirty percent of surgeons, 27% of pulmonologists and 44% of
      radiation oncologists indicated that doctors are not properly trained to
      implement SDM in clinical practice (P-value = 0.37). SDM may not always be
      feasible due to low patient education level and minimal knowledge about lung
      cancer. Wide variations in the clinicians' lung cancer treatment preferences were
      observed in the responses to the hypothetical cases. CONCLUSIONS: In current
      clinical decision making in lung cancer treatment, a majority of clinicians agree
      that it is important to involve lung cancer patients in treatment decision making
      but that time constraints and the inability of some patients to make a weighted
      decision are important barriers. The observed variation in lung cancer treatment
      preferences among clinicians suggests that for most patients both surgery and
      radiotherapy are suitable options, and it underlines the sensitive nature of
      treatment choices in early-stage non-small-cell lung cancer.

PMID- 28449095
TI  - Role of chemokine (C-C motif) ligand 24 in spatial arrangement of the inner cell
      mass of the bovine embryo.
AB  - The process of spatial rearrangement of cells of the inner cell mass (ICM) that
      are destined to become hypoblast is not well understood. The observation that the
      chemokine (C-C motif) ligand 24 (CCL24) and several other genes involved in
      chemokine signaling are expressed more in the ICM than in the trophectoderm of
      the bovine embryo resulted in the hypothesis that CCL24 participates in spatial
      organization of the ICM. Temporally, expression of CCL24 in the bovine embryo
      occurs coincidently with blastocyst formation: transcript abundance was low until
      the late morula stage, peaked in the blastocyst at Day 7 of development and
      declined by Day 9. Treatment of embryos with two separate antagonists of C-C
      motif chemokine receptor 3 (the prototypical receptor for CCL24) decreased the
      percent of GATA6+ cells (hypoblast precursors) that were located in the outside
      of the ICM. Similarly, injection of zygotes with a CCL24-specific morpholino
      decreased the percent of GATA6+ cells in the outside of the ICM. In conclusion,
      CCL24 assists in spatial arrangement of the ICM in the bovine embryo. This
      experiment points to new functions of chemokine signaling in the bovine embryo
      and is consistent with the idea that cell migration is involved in the spatial
      organization of hypoblast cells in the blastocyst.

PMID- 28449094
TI  - Hepatic Tm6sf2 overexpression affects cellular ApoB-trafficking, plasma lipid
      levels, hepatic steatosis and atherosclerosis.
AB  - The human transmembrane 6 superfamily member 2 (TM6SF2) gene has been implicated
      in plasma lipoprotein metabolism, alcoholic and non-alcoholic fatty liver disease
      and myocardial infarction in multiple genome-wide association studies. To
      investigate the role of Tm6sf2 in metabolic homeostasis, we generated mice with
      elevated expression using adeno-associated virus (AAV)-mediated gene delivery.
      Hepatic overexpression of mouse Tm6sf2 resulted in phenotypes previously observed
      in Tm6sf2-deficient mice including reduced plasma lipid levels, diminished
      hepatic triglycerides secretion and increased hepatosteatosis. Furthermore,
      increased hepatic Tm6sf2 expression protected against the development of
      atherosclerosis in LDL-receptor/ApoB48-deficient mice. In cultured human
      hepatocytes, Tm6sf2 overexpression reduced apolipoprotein B secretion and
      resulted in its accumulation within the endoplasmic reticulum (ER) suggesting
      impaired ER-to-Golgi trafficking of pre-very low-density lipoprotein (VLDL)
      particles. Analysis of two metabolic trait-associated coding polymorphisms in the
      human TM6SF2 gene (rs58542926 and rs187429064) revealed that both variants impact
      TM6SF2 expression by affecting the rate of protein turnover. These data
      demonstrate that rs58542926 (E167K) and rs187429064 (L156P) are functional
      variants and suggest that they influence metabolic traits through altered TM6SF2
      protein stability. Taken together, our results indicate that cellular Tm6sf2
      level is an important determinant of VLDL metabolism and further implicate TM6SF2
      as a causative gene underlying metabolic disease and trait associations at the
      19p13.11 locus.

PMID- 28449096
TI  - Two ribosome recruitment sites direct multiple translation events within HIV1 Gag
      open reading frame.
AB  - In the late phase of the HIV virus cycle, the unspliced genomic RNA is exported
      to the cytoplasm for the necessary translation of the Gag and Gag-pol
      polyproteins. Three distinct translation initiation mechanisms ensuring Gag
      production have been described with little rationale for their multiplicity. The
      Gag-IRES has the singularity to be located within Gag ORF and to directly
      interact with ribosomal 40S. Aiming at elucidating the specificity and the
      relevance of this interaction, we probed HIV-1 Gag-IRES structure and developed
      an innovative integrative modelling strategy to take into account all the
      gathered information. We propose a novel Gag-IRES secondary structure strongly
      supported by all experimental data. We further demonstrate the presence of two
      regions within Gag-IRES that independently and directly interact with the
      ribosome. Importantly, these binding sites are functionally relevant to Gag
      translation both in vitro and ex vivo. This work provides insight into the Gag
      IRES molecular mechanism and gives compelling evidence for its physiological
      importance. It allows us to propose original hypotheses about the IRES
      physiological role and conservation among primate lentiviruses.

PMID- 28449097
TI  - Creating a Culture of Collaboration: A Brief History of Academic Neurosurgery in
      Washington, DC.
AB  - Clinical neurosurgery has been practiced in the US capital for just over 100
      years. As former residents and fellows of Drs. Harvey Cushing and Walter Dandy
      moved to the region, hospitals at Georgetown and George Washington Universities
      became early adopters of this new surgical discipline. Later academic
      neurosurgery programs were established at the National Institutes of Health,
      Walter Reed Medical Center, and Children's National Medical Center. Neurosurgical
      pioneers at these institutions developed new technologies and diagnostic
      procedures which continue to inform our current practice. In addition, continued
      collaboration between the multiple training sites in Washington, DC has uniquely
      enriched our residents' training experience.

PMID- 28449099
TI  - Connexin37 reduces smooth muscle cell proliferation and intimal hyperplasia in a
      mouse model of carotid artery ligation.
AB  - Aims: Intimal hyperplasia (IH) is an abnormal response to vessel injury
      characterized by the dedifferentiation, migration, and proliferation of quiescent
      vascular smooth muscle cells (VSMC) to form a neointima layer. Vascular connexins
      (Cx) are involved in the pathophysiology of various vascular diseases, and Cx43,
      the main Cx expressed in VSMC, has been shown to promote VSMC proliferation and
      IH. The aim of this study was to investigate the participation of another Cx,
      namely Cx37, in the formation of the neointima layer. Methods and results: Wild
      type (WT) and Cx37-deficient (Cx37-/-) C57BL/6J mice were subjected to carotid
      artery ligation (CAL), a model of vessel injury and IH. The neointima developed
      linearly in WT until 28 days post surgery. In contrast, the neointima layer was
      almost absent 14 days after surgery in Cx37-/- mice, and twice as more developed
      after 28 days compared to WT mice. This large neointima formation correlated with
      a two-fold increase in cell proliferation in the media and neointima regions
      between 14 and 28 days in Cx37-/- mice compared to WT mice. The CAL triggered
      Cx43 overexpression in the media and neointima layers of ligated carotids in WT
      mice, and selectively up-regulated Cx37 expression in the media layer, but not in
      the neointima layer. The de novo expression of Cx37 in human primary VSMC reduced
      cell proliferation and P-Akt levels, in association with lower Cx43 levels,
      whereas Cx43 overexpression increased P-Akt levels. Conclusion: The presence of
      Cx37 in the media layer of injured arteries restrains VSMC proliferation and
      limits the development of IH, presumably by interfering with the pro
      proliferative effect of Cx43 and the Akt pathway.

PMID- 28449101
TI  - Synthetic biology approaches for the production of plant metabolites in
      unicellular organisms.
AB  - Synthetic biology is the repurposing of biological systems for novel objectives
      and applications. Through the co-ordinated and balanced expression of genes, both
      native and those introduced from other organisms, resources within an industrial
      chassis can be siphoned for the commercial production of high-value commodities.
      This developing interdisciplinary field has the potential to revolutionize
      natural product discovery from higher plants, by providing a diverse array of
      tools, technologies, and strategies for exploring the large chemically complex
      space of plant natural products using unicellular organisms. In this review, we
      emphasize the key features that influence the generation of biorefineries and
      highlight technologies and strategic solutions that can be used to overcome
      engineering pitfalls with rational design. Also presented is a succinct guide to
      assist the selection of unicellular chassis most suited for the engineering and
      subsequent production of the desired natural product, in order to meet the global
      demand for plant natural products in a safe and sustainable manner.

PMID- 28449098
TI  - Insights on persistent airway infection by non-typeable Haemophilus influenzae in
      chronic obstructive pulmonary disease.
AB  - Non-typeable Haemophilus influenzae (NTHi) is the most common bacterial cause of
      infection of the lower airways in adults with chronic obstructive pulmonary
      disease (COPD). Infection of the COPD airways causes acute exacerbations,
      resulting in substantial morbidity and mortality. NTHi has evolved multiple
      mechanisms to establish infection in the hostile environment of the COPD airways,
      allowing the pathogen to persist in the airways for months to years. Persistent
      infection of the COPD airways contributes to chronic airway inflammation that
      increases symptoms and accelerates the progressive loss of pulmonary function,
      which is a hallmark of the disease. Persistence mechanisms of NTHi include the
      expression of multiple redundant adhesins that mediate binding to host cellular
      and extracellular matrix components. NTHi evades host immune recognition and
      clearance by invading host epithelial cells, forming biofilms, altering gene
      expression and displaying surface antigenic variation. NTHi also binds host serum
      factors that confer serum resistance. Here we discuss the burden of COPD and the
      role of NTHi infections in the course of the disease. We provide an overview of
      NTHi mechanisms of persistence that allow the pathogen to establish a niche in
      the hostile COPD airways.

PMID- 28449100
TI  - Integrated analysis of individual codon contribution to protein biosynthesis
      reveals a new approach to improving the basis of rational gene design.
AB  - Gene codon optimization may be impaired by the misinterpretation of frequency and
      optimality of codons. Although recent studies have revealed the effects of codon
      usage bias (CUB) on protein biosynthesis, an integrated perspective of the
      biological role of individual codons remains unknown. Unlike other previous
      studies, we show, through an integrated framework that attributes of codons such
      as frequency, optimality and positional dependency should be combined to unveil
      individual codon contribution for protein biosynthesis. We designed a codon
      quantification method for assessing CUB as a function of position within genes
      with a novel constraint: the relativity of position-dependent codon usage shaped
      by coding sequence length. Thus, we propose a new way of identifying the
      enrichment, depletion and non-uniform positional distribution of codons in
      different regions of yeast genes. We clustered codons that shared attributes of
      frequency and optimality. The cluster of non-optimal codons with rare occurrence
      displayed two remarkable characteristics: higher codon decoding time than
      frequent-non-optimal cluster and enrichment at the 5'-end region, where optimal
      codons with the highest frequency are depleted. Interestingly, frequent codons
      with non-optimal adaptation to tRNAs are uniformly distributed in the
      Saccharomyces cerevisiae genes, suggesting their determinant role as a speed
      regulator in protein elongation.

PMID- 28449102
TI  - Enhancing expression of SSU1 genes in Saccharomyces uvarum leads to an increase
      in sulfite tolerance and a transcriptome profile change.
AB  - Saccharomyces uvarum is a good wine yeast species that may have great potential
      for the future. However, sulfur tolerance of most S. uvarum strains is very poor.
      In addition there is still little information about the SSU1 gene of S. uvarum,
      which encodes a putative transporter conferring sulfite tolerance. In order to
      analyze the function of the SSU1 gene, two expression vectors that contained
      different SSU1 genes were constructed and transferred into a sulfite-tolerant S.
      uvarum strain, A9. Then sulfite tolerance, SO2 production, and PCR, sequencing,
      RT-qPCR and transcriptome analyses were used to access the function of the S.
      uvarum SSU1 gene. Our results illustrated that enhancing expression of the SSU1
      gene can promote sulfite resistance in S. uvarum, and an insertion fragment ahead
      of the additional SSU1 gene, as seen in some alleles, could affect the expression
      of other genes and the sulfite tolerance level of S. uvarum. This is the first
      report on enhancing the expression of the SSU1 gene of S. uvarum.

PMID- 28449104
TI  - Liquid Chromatographic-Chemometric Techniques for the Simultaneous HPLC
      Determination of Lansoprazole, Amoxicillin and Clarithromycin in Commercial
      Preparation.
AB  - Two multivariate calibration-prediction techniques, principal component
      regression (PCR) and partial least-squares regression (PLSR) were applied to the
      chromatographic multicomponent analysis of the drug containing lansoprazole
      (LAN), clarithromycin (CLA) and amoxicillin (AMO). Optimum chromatographic
      separation of LAN, CLA and AMO with atorvastatin as the internal standard (IS)
      was obtained by using Xterra(r) RP18 column 5 MUm 4.6 * 250 mm2, and 25 mM
      ammonium chloride buffer prepared ammonium chloride, acetonitrile and bidistilled
      water (45:45:10 v/v) as the mobile phase at flow rate 1.0 mL/min. The high
      pressure liquid chromatography data sets consisting of the ratios of analyte peak
      areas to the IS peak area were obtained by using diode array detector detection
      at five wavelengths (205, 210, 215, 220 and 225 nm). LC-chemometric calibration
      for LAN, CLA and AMO were separately constructed by using the relationship
      between the peak-area ratio and training sets for each analyte. A series of
      synthetic solutions containing different concentrations of LAN, CLA and AMO were
      used to check the prediction ability of the PCR and PLS. Both of the two
      chemometric methods in this study can be satisfactorily used for the quantitative
      analysis and for dissolutions tests of multicomponent commercial drug.

PMID- 28449105
TI  - Family Communication Styles and Resilience among Adolescents.
AB  - Some adolescents manage to be resilient, whereas others develop posttraumatic
      stress disorder (PTSD) symptoms after experiencing trauma, but the mechanisms
      underlying these differences are unclear. Public secondary school students (N =
      98) referred for counseling completed questionnaires assessing exposure to
      stressful events, family communication, and PTSD. Seventy percent of the sample
      reported PTSD symptoms in the clinical range. Open family communication was
      negatively associated with female gender, problem family communication (PFC), and
      PTSD symptom severity. PFC was positively associated with female gender, number
      of stressful events, and PTSD symptom severity. Family storytelling style had a
      negative association with age, PFC, and avoidance symptoms. In the full
      regression model only the number of life events and PFC appeared to have an
      independent effect on PTSD symptom severity. Results indicate that exposure to
      stressful life events and poor family communication are associated with increased
      risk for PTSD symptoms. Findings may be useful in family-focused approaches to
      treating adolescents with trauma histories and highlighting the importance of
      PTSD screening in school-based counseling.

PMID- 28449103
TI  - Novel degenerative and developmental defects in a zebrafish model of
      mucolipidosis type IV.
AB  - Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by
      neurologic and ophthalmologic abnormalities. There is currently no effective
      treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from
      the transient receptor potential (TRP) family. In this study, we used genome
      editing to knockout the two mcoln1 genes present in Danio rerio (zebrafish). Our
      model successfully reproduced the retinal and neuromuscular defects observed in
      MLIV patients, indicating that this model is suitable for studying the disease
      pathogenesis. Importantly, our model revealed novel insights into the origins and
      progression of the MLIV pathology, including the contribution of autophagosome
      accumulation to muscle dystrophy and the role of mcoln1 in embryonic development,
      hair cell viability and cellular maintenance. The generation of a MLIV model in
      zebrafish is particularly relevant given the suitability of this organism for
      large-scale in vivo drug screening, thus providing unprecedented opportunities
      for therapeutic discovery.

PMID- 28449106
TI  - MicrobiomeAnalyst: a web-based tool for comprehensive statistical, visual and
      meta-analysis of microbiome data.
AB  - The widespread application of next-generation sequencing technologies has
      revolutionized microbiome research by enabling high-throughput profiling of the
      genetic contents of microbial communities. How to analyze the resulting large
      complex datasets remains a key challenge in current microbiome studies. Over the
      past decade, powerful computational pipelines and robust protocols have been
      established to enable efficient raw data processing and annotation. The focus has
      shifted toward downstream statistical analysis and functional interpretation.
      Here, we introduce MicrobiomeAnalyst, a user-friendly tool that integrates recent
      progress in statistics and visualization techniques, coupled with novel knowledge
      bases, to enable comprehensive analysis of common data outputs produced from
      microbiome studies. MicrobiomeAnalyst contains four modules - the Marker Data
      Profiling module offers various options for community profiling, comparative
      analysis and functional prediction based on 16S rRNA marker gene data; the
      Shotgun Data Profiling module supports exploratory data analysis, functional
      profiling and metabolic network visualization of shotgun metagenomics or
      metatranscriptomics data; the Taxon Set Enrichment Analysis module helps
      interpret taxonomic signatures via enrichment analysis against >300 taxon sets
      manually curated from literature and public databases; finally, the Projection
      with Public Data module allows users to visually explore their data with a public
      reference data for pattern discovery and biological insights. MicrobiomeAnalyst
      is freely available at http://www.microbiomeanalyst.ca.

PMID- 28449107
TI  - The Role of Dyadic Confidence on Engagement in Heart Failure Care Behaviors.
AB  - Background and Objectives: Increasingly, older adults and their families are
      expected to manage complex conditions with little support. In the case of heart
      failure (HF), symptom monitoring and management are critical in preventing acute
      exacerbations and poor clinical outcomes. The current study examined the role of
      dyadic confidence on engagement in HF care behaviors by patients and their
      spouses. Research Design and Methods: A cross-sectional design was used to
      examine 60 couples living with HF. Three dyadic confidence variables were created
      to represent average level of confidence, gap in confidence, and direction of gap
      within each couple. A series of multilevel models were used to examine dyadic
      engagement in HF maintenance, management, and consulting behaviors and the role
      of dyadic confidence. Results: Patients were significantly more engaged in HF
      maintenance behaviors than spouses; couples were more collaborative in their
      engagement in HF management and consulting behaviors. Average level of confidence
      in the dyad was significantly associated with patient engagement in all three HF
      behaviors. Spouse engagement was associated with more congruence in confidence
      and having higher levels of confidence than their partners with HF. Women were
      significantly more engaged in HF behaviors than men, regardless of role.
      Discussion and Implications: The study employed a dyadic approach to HF care and
      a novel approach to confidence. Findings confirm the social nature of confidence
      and its important role in HF. Clinicians have opportunities to optimize patient
      outcomes by fostering greater collaboration within couples.

PMID- 28449109
TI  - Detection of G-quadruplex DNA in mammalian cells.

PMID- 28449108
TI  - Poly(A)-ClickSeq: click-chemistry for next-generation 3?-end sequencing without
      RNA enrichment or fragmentation.
AB  - The recent emergence of alternative polyadenylation (APA) as an engine driving
      transcriptomic diversity has stimulated the development of sequencing
      methodologies designed to assess genome-wide polyadenylation events. The goal of
      these approaches is to enrich, partition, capture and ultimately sequence poly(A)
      site junctions. However, these methods often require poly(A) enrichment, 3?
      linker ligation steps, and RNA fragmentation, which can necessitate higher levels
      of starting RNA, increase experimental error and potentially introduce bias. We
      recently reported a click-chemistry based method for generating RNAseq libraries
      called 'ClickSeq'. Here, we adapt this method to direct the cDNA synthesis
      specifically toward the 3?UTR/poly(A) tail junction of cellular RNA. With this
      novel approach, we demonstrate sensitive and specific enrichment for poly(A) site
      junctions without the need for complex sample preparation, fragmentation or
      purification. Poly(A)-ClickSeq (PAC-seq) is therefore a simple procedure that
      generates high-quality RNA-seq poly(A) libraries. As a proof-of-principle, we
      utilized PAC-seq to explore the poly(A) landscape of both human and Drosophila
      cells in culture and observed outstanding overlap with existing poly(A) databases
      and also identified previously unannotated poly(A) sites. Moreover, we utilize
      PAC-seq to quantify and analyze APA events regulated by CFIm25 illustrating how
      this technology can be harnessed to identify alternatively polyadenylated RNA.

PMID- 28449111
TI  - Migrant women living with HIV in Europe: are they facing inequalities in the
      prevention of mother-to-child-transmission of HIV?: The European Pregnancy and
      Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.
AB  - Background: In pregnancy early interventions are recommended for prevention of
      mother-to-child-transmission (PMTCT) of HIV. We examined whether pregnant women
      who live with HIV in Europe and are migrants encounter barriers in accessing HIV
      testing and care. Methods: Four cohorts within the European Pregnancy and
      Paediatric HIV Cohort Collaboration provided data for pooled analysis of 11 795
      pregnant women who delivered in 2002-12 across ten European countries. We defined
      a migrant as a woman delivering in a country different from her country of birth
      and grouped the countries into seven world regions. We compared three suboptimal
      PMTCT interventions (HIV diagnosis in late pregnancy in women undiagnosed at
      conception, late anti-retroviral therapy (ART) start in women diagnosed but
      untreated at conception and detectable viral load (VL) at delivery in women on
      antenatal ART) in native and migrant women using multivariable logistic
      regression models. Results: Data included 9421 (79.9%) migrant women, mainly from
      sub-Saharan Africa (SSA); 4134 migrant women were diagnosed in the current
      pregnancy, often (48.6%) presenting with CD4 count <350 cells/ul. Being a migrant
      was associated with HIV diagnosis in late pregnancy [OR for SSA vs. native women,
      2.12 (95% CI 1.67, 2.69)] but not with late ART start if diagnosed but not on ART
      at conception, or with detectable VL at delivery once on ART. Conclusions:
      Migrant women were more likely to be diagnosed in late pregnancy but once on ART
      virological response was good. Good access to antenatal care enables the
      implementation of PMTCT protocols and optimises both maternal and children health
      outcomes generally.

PMID- 28449110
TI  - veqtl-mapper: variance association mapping for molecular phenotypes.
AB  - Motivation: Genetic loci associated with the variance of phenotypic traits have
      been of recent interest as they can be signatures of genetic interactions, gene
      by environment interactions, parent of origin effects and canalization. We
      present a fast efficient tool to map loci affecting variance of gene expression
      and other molecular phenotypes in cis. Results: Applied to the publicly available
      Geuvadis gene expression dataset, we identify 816 loci associated with variance
      of gene expression using an additive model, and 32 showing differences in
      variance between homozygous and heterozygous alleles, signatures of parent of
      origin effects. Availability and implementation: Documentation and links to
      source code and binaries for linux can be found at
      https://funpopgen.github.io/veqm/ . Contact: andrew.brown@unige.ch. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28449112
TI  - Phenotypic Variability of the Amazonian Species Rhodnius brethesi (Hemiptera:
      Reduviidae).
AB  - The wild species Rhodnius brethesi (Matta, 1919) (Hemiptera: Reduviidae) is found
      in areas of piassabais in microregion of Rio Negro, Amazonas, Brazil. Its
      geographical distribution overlaps the areas of Leopoldinia piassaba palm. In
      areas where palm trees are found, transmission cycle of Trypanosoma cruzi is
      related to the extractive activity of the palm fiber, exposing workers to wild
      vector transmission of this parasite. The close association with the palm tree L.
      piassaba suggests that this wild triatomine has special features in its sensory
      system allowing specificity of ecotope. The objective of the study is to identify
      the antennal sensilla phenotype and morphologically characterize the size and
      shape of the wings of wild R. brethesi, and to compare with the phenotype present
      in individuals reared in the laboratory. From the samples taken in the field, the
      presence of the species R. brethesi was found on both banks of the Rio Negro. The
      techniques used to verify the morphological patterns are important resources for
      observations of the triatomine populations, be they in an artificial or natural
      habitat.

PMID- 28449113
TI  - Development of a New Clinical Severity Staging System for Patients With
      Nonmetastatic Papillary Thyroid Carcinoma.

PMID- 28449114
TI  - Neuro-symbolic representation learning on biological knowledge graphs.
AB  - Motivation: Biological data and knowledge bases increasingly rely on Semantic Web
      technologies and the use of knowledge graphs for data integration, retrieval and
      federated queries. In the past years, feature learning methods that are
      applicable to graph-structured data are becoming available, but have not yet
      widely been applied and evaluated on structured biological knowledge. Results: We
      develop a novel method for feature learning on biological knowledge graphs. Our
      method combines symbolic methods, in particular knowledge representation using
      symbolic logic and automated reasoning, with neural networks to generate
      embeddings of nodes that encode for related information within knowledge graphs.
      Through the use of symbolic logic, these embeddings contain both explicit and
      implicit information. We apply these embeddings to the prediction of edges in the
      knowledge graph representing problems of function prediction, finding candidate
      genes of diseases, protein-protein interactions, or drug target relations, and
      demonstrate performance that matches and sometimes outperforms traditional
      approaches based on manually crafted features. Our method can be applied to any
      biological knowledge graph, and will thereby open up the increasing amount of
      Semantic Web based knowledge bases in biology to use in machine learning and data
      analytics. Availability and implementation: https://github.com/bio-ontology
      research-group/walking-rdf-and-owl. Contact: robert.hoehndorf@kaust.edu.sa.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28449115
TI  - Estimation of State-Level Prevalence of Hepatitis C Virus Infection, US States
      and District of Columbia, 2010.
AB  - Background.: Hepatitis C virus (HCV) infection is the most common chronic blood
      borne infection in the United States and a leading cause of morbidity and
      mortality. Previous analyses of the US National Health and Nutrition Examination
      Survey (NHANES) indicated approximately 3.6 million noninstitutionalized persons
      with antibody to HCV (anti-HCV). However, state-level prevalence remains less
      understood and cannot be estimated reliably from NHANES alone. Methods.: We used
      3 publicly available government data sources to estimate anti-HCV prevalence in
      each US state among noninstitutionalized persons aged >=18 years. A small-area
      estimation model combined indirect standardization of NHANES-based prevalence
      with logistic regression modeling of mortality data, listing acute or chronic HCV
      infection as a cause of death, from the National Vital Statistics System during
      1999-2012. Model results were combined with US Census population sizes to
      estimate total number and prevalence of persons with antibody to HCV in 2010.
      Results.: National anti-HCV prevalence was 1.67% (95% confidence interval [CI],
      1.53-1.90), or 3 911 800 (95% CI, 3 589 400- 4 447 500) adults in 2010. State
      specific prevalence ranged from 0.71% (Illinois) to 3.34% (Oklahoma). The West
      census region had the highest region-specific prevalence (2.14% [95% CI, 1.96
      2.48]); 10 of 13 states had rates above the national average. The South had the
      highest number of persons with anti-HCV (n = 1561600 [95% CI, 1 427 700-1 768
      900]). The Midwest had the lowest region-specific prevalence (1.14% [95% CI,
      1.04%-1.30%]). Conclusions.: States in the US West and South have been most
      impacted by hepatitis C. Estimates of HCV infection burden are essential to guide
      policy and programs to optimally prevent, detect, and cure infection.

PMID- 28449117
TI  - The LXR Ligand T0901317 Acutely Inhibits Insulin Secretion by Affecting
      Mitochondrial Metabolism.
AB  - The role of liver X receptor (LXR) in pancreatic beta-cell physiology and
      pathophysiology is still unclear. It has been postulated that chronic LXR
      activation in beta-cells induces lipotoxicity, a key step in the development of
      beta-cell dysfunction, which accompanies type 2 diabetes mellitus. In most of
      these studies, the LXR ligand T0901317 has been administered chronically in the
      micromolar range to study the significance of LXR activation. In the current
      study, we have evaluated acute effects of T0901317 on stimulus-secretion coupling
      of beta-cells. We found that 10 uM T0901317 completely suppressed oscillations of
      the cytosolic Ca2+ concentration induced by 15 mM glucose. Obviously, this effect
      was due to inhibition of mitochondrial metabolism. T0901317 markedly depolarized
      the mitochondrial membrane potential, thus inhibiting adenosine triphosphate
      (ATP) production and reducing the cytosolic ATP concentration. This led in turn
      to a huge increase in KATP current and hyperpolarization of the cell membrane
      potential. Eventually, T0901317 inhibited glucose-induced insulin secretion.
      These effects were rapid in on-set and not compatible with the activation of a
      nuclear receptor. In vivo, T0901317 acutely increased the blood glucose
      concentration after intraperitoneal application. In summary, these data clearly
      demonstrate that T0901317 exerts acute effects on stimulus-secretion coupling.
      This observation questions the chronic use of T0901317 and limits the
      interpretation of results obtained under these experimental conditions.

PMID- 28449116
TI  - The iconography of mourning and its neural correlates: a functional neuroimaging
      study.
AB  - The present functional neuroimaging study focuses on the iconography of mourning.
      A culture-specific pattern of body postures of mourning individuals, mostly
      suggesting withdrawal, emerged from a survey of visual material. When used in
      different combinations in stylized drawings in our neuroimaging study, this
      material activated cortical areas commonly seen in studies of social cognition
      (temporo-parietal junction, superior temporal gyrus, and inferior temporal lobe),
      empathy for pain (somatosensory cortex), and loss (precuneus, middle/posterior
      cingular gyrus). This pattern of activation developed over time. While in the
      early phases of exposure lower association areas, such as the extrastriate body
      area, were active, in the late phases activation in parietal and temporal
      association areas and the prefrontal cortex was more prominent. These findings
      are consistent with the conventional and contextual character of iconographic
      material, and further differentiate it from emotionally negatively valenced and
      high-arousing stimuli. In future studies, this neuroimaging assay may be useful
      in characterizing interpretive appraisal of material of negative emotional
      valence.

PMID- 28449118
TI  - Polyphosphate-accumulating bacterial community colonizing the calcium bodies of
      terrestrial isopod crustaceans Titanethes albus and Hyloniscus riparius.
AB  - Terrestrial isopods from the group Trichoniscidae accumulate calcium in
      specialized organs, known as the calcium bodies. These consist of two pairs of
      epithelial sacs located alongside the digestive system. These organs contain
      various forms of calcium and constantly present bacteria. To elucidate their
      origin and role, we analyzed the bacteria of the calcium bodies in the cave
      dwelling isopod Titanethes albus and the epigean species Hyloniscus riparius, by
      microscopy, histochemistry, energy dispersive X-ray spectrometry, 16S rRNA
      analysis and in situ hybridization. The calcium bodies of both species comprise
      numerous and diverse bacterial communities consisting of known soil bacteria.
      Despite their diversity, these bacteria share the polyphosphate-accumulation
      ability. We present the model of phosphorous dynamics in the calcium bodies
      during the molting cycle and potentially beneficial utilization of the symbiotic
      phosphate by the host in cyclic regeneration of the cuticle. Although not fully
      understood, this unique symbiosis represents the first evidence of polyphosphate
      accumulating bacterial symbionts in the tissue of a terrestrial animal.

PMID- 28449119
TI  - Mutations in THAP11 cause an inborn error of cobalamin metabolism and
      developmental abnormalities.
AB  - CblX (MIM309541) is an X-linked recessive disorder characterized by defects in
      cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in
      HCFC1, a transcriptional co-regulator which interacts with multiple transcription
      factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via
      the regulation of MMACHC expression through its interaction with THAP11, a THAP
      domain-containing transcription factor. The HCFC1/THAP11 complex potentially
      regulates genes involved in diverse cellular functions including cell cycle,
      proliferation, and transcription. Thus, it is likely that mutation of THAP11 also
      results in biochemical and other phenotypes similar to those observed in patients
      with cblX. We report a patient who presented with clinical and biochemical
      phenotypic features that overlap cblX, but who does not have any mutations in
      either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a
      potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional
      analysis in the developing zebrafish embryo demonstrated that both THAP11 and
      HCFC1 regulate the proliferation and differentiation of neural precursors,
      suggesting important roles in normal brain development. The loss of THAP11 in
      zebrafish embryos results in craniofacial abnormalities including the complete
      loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial
      cartilages. These data are consistent with our previous work that demonstrated a
      role for HCFC1 in vertebrate craniofacial development. High throughput RNA
      sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11.
      Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin
      metabolism as well as other pathways involved in early vertebrate development.

PMID- 28449120
TI  - SigSeeker: a peak-calling ensemble approach for constructing epigenetic
      signatures.
AB  - Motivation: Epigenetic data are invaluable when determining the regulatory
      programs governing a cell. Based on use of next-generation sequencing data for
      characterizing epigenetic marks and transcription factor binding, numerous peak
      calling approaches have been developed to determine sites of genomic significance
      in these data. Such analyses can produce a large number of false positive
      predictions, suggesting that sites supported by multiple algorithms provide a
      stronger foundation for inferring and characterizing regulatory programs
      associated with the epigenetic data. Few methodologies integrate epigenetic based
      predictions of multiple approaches when combining profiles generated by different
      tools. Results: The SigSeeker peak-calling ensemble uses multiple tools to
      identify peaks, and with user-defined thresholds for peak overlap and signal
      strength it retains only those peaks that are concordant across multiple tools.
      Peaks predicted to be co-localized by only a very small number of tools,
      discovered to be only marginally overlapping, or found to represent significant
      outliers to the approximation model are removed from the results, providing
      concise and high quality epigenetic datasets. SigSeeker has been validated using
      established benchmarks for transcription factor binding and histone modification
      ChIP-Seq data. These comparisons indicate that the quality of our ensemble
      technique exceeds that of single tool approaches, enhances existing peak-calling
      ensembles, and results in epigenetic profiles of higher confidence. Availability
      and implementation: http://sigseeker.org. Contact: lichtenbergj@mail.nih.gov.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28449121
TI  - Tri-directional anaphases as a novel chromosome segregation defect in human
      oocytes.
AB  - STUDY QUESTION: What are the chromosome segregation errors in human oocyte
      meiosis-I that may underlie oocyte aneuploidy? SUMMARY ANSWER: Multiple modes of
      chromosome segregation error were observed, including tri-directional anaphases,
      which we attribute to loss of bipolar spindle structure at anaphase-I. WHAT IS
      KNOWN ALREADY: Oocyte aneuploidy is common and associated with infertility, but
      mechanistic information on the chromosome segregation errors underlying these
      defects is scarce. Lagging chromosomes were recently reported as a possible
      mechanism by which segregation errors occur. STUDY DESIGN, SIZE, DURATION: Long
      term confocal imaging of chromosome dynamics in 50 human oocytes collected
      between January 2015 and May 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Germinal vesicle (GV) stage oocytes were collected from women undergoing
      intracytoplasmic sperm injection cycles and also CD1 mice. Oocytes were
      microinjected with complementary RNAs to label chromosomes, and in a subset of
      oocytes, the meiotic spindle. Oocytes were imaged live through meiosis-I using
      confocal microscopy. 3D image reconstruction was used to classify chromosome
      segregation phenotypes at anaphase-I. Segregation phenotypes were related to
      spindle dynamics and cell cycle timings. MAIN RESULTS AND THE ROLE OF CHANCE:
      Most (87%) mouse oocytes segregated chromosomes with no obvious defects. We found
      that 20% of human oocytes segregated chromosomes bi-directionally with no lagging
      chromosomes. The rest were categorised as bi-directional anaphase with lagging
      chromosomes (20%), bi-directional anaphase with chromatin mass separation (34%)
      or tri-directional anaphase (26%). Segregation errors correlated with chromosome
      misalignment prior to anaphase. Spindles were tripolar when tri-directional
      anaphases occurred. Anaphase phenotypes did not correlate with meiosis-I duration
      (P = 0.73). LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION:
      Oocytes were recovered at GV stage after gonadotrophin-stimulation, and the usual
      oocyte quality caveats apply. Whilst the possibility that imaging may affect
      oocyte physiology cannot be formally excluded, detailed controls and
      justifications are presented. WIDER IMPLICATIONS OF THE FINDINGS: This is one of
      the first reports of live imaging of chromosome dynamics in human oocytes,
      introducing tri-directional anaphases as a novel potential mechanism for oocyte
      aneuploidy. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by grants
      from Fondation Jean-Louis Levesque (Canada), CIHR (MOP142334) and CFI (32711) to
      GF. JH is supported by Postdoctoral Fellowships from The Lalor Foundation and
      CIHR (146703). The authors have no conflict of interest.

PMID- 28449122
TI  - Up-regulation of NCED3 and ABA biosynthesis occur within minutes of a decrease in
      leaf turgor but AHK1 is not required.
AB  - A major environmental signal influencing day-time stomatal aperture is the vapour
      pressure deficit between the leaf and atmosphere (VPD). In angiosperms, increased
      VPD triggers biosynthesis of abscisic acid (ABA), prompting rapid stomatal
      closure. Altered cell turgor has been proposed as the trigger for ABA
      biosynthesis, but the timing and nature of the genetic signals linking these
      processes have remained uncertain. We investigated this in Arabidopsis by
      examining changes induced by a decrease in leaf turgor, simulating a natural
      increase in VPD. We found that the rate-limiting gene within the de novo ABA
      biosynthesis pathway, 9-cis-epoxycarotenoid dioxygenase 3 (NCED3), was induced
      and ABA levels increased within just 5 min of decreased leaf turgor. This rapid
      induction matches the time-frame for initiation of stomatal closure in response
      to a doubling in VPD. We further examined Arabidopsis histidine kinase1 (AHK1) as
      the most likely candidate for the turgor-sensing receptor involved, but found no
      significant difference between wild-type and an ahk1 null mutant in the induction
      of ABA-biosynthetic genes, ABA production, or stomatal behaviour. We show that
      decreased leaf turgor triggers de novo ABA biosynthesis within the time-frame of
      the stomatal response to VPD, but that AHK1 does not fulfil a critical role as a
      turgor-sensing receptor within this pathway.

PMID- 28449123
TI  - Capturing a mammalian DNA polymerase extending from an oxidized nucleotide.
AB  - The oxidized nucleotide, 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-oxoG), is one of
      the most abundant DNA lesions. 8-oxoG plays a major role in tumorigenesis and
      human disease. Biological consequences of 8-oxoG are mediated in part by its
      insertion into the genome, making it essential to understand how DNA polymerases
      handle 8-oxoG. Insertion of 8-oxoG is mutagenic when opposite adenine but not
      when opposite cytosine. However, either result leads to DNA damage at the primer
      terminus (3?-end) during the succeeding insertion event. Extension from DNA
      damage at primer termini remains poorly understood. Using kinetics and time-lapse
      crystallography, we evaluated how a model DNA polymerase, human polymerase beta,
      accommodates 8-oxoG at the primer terminus opposite cytosine and adenine.
      Notably, extension from the mutagenic base pair is favored over the non-mutagenic
      base pair. When 8-oxoG is at the primer terminus opposite cytosine, DNA centric
      changes lead to a clash between O8 of 8-oxoG and the phosphate backbone. Changes
      in the extension reaction resulting from the altered active site provide evidence
      for a stabilizing interaction between Arg254 and Asp256 that serves an important
      role during DNA synthesis reactions. These results provide novel insights into
      the impact of damage at the primer terminus on genomic stability and DNA
      synthesis.

PMID- 28449124
TI  - Labia Majora Augmentation: A Systematic Review of the Literature.
AB  - Background: Currently, there is no standardized approach for labia majora
      augmentation and controversies still exist regarding this subject. Objectives:
      This systematic review aimed to assess the evidence in the literature regarding
      labia majora augmentation. Methods: On November 20, 2016, we conducted an online
      search of published articles in the Medline, Embase, and Cochrane databases. All
      articles describing labia majora augmentation were included in this review.
      Results: Nine studies were selected for inclusion in the systematic review. Only
      2 studies were prospective trials. The most commonly used technique was fat
      grafting with a total of 4 articles and 183 patients. The mean total injected fat
      volume ranged from 18 mL to 120 mL per session. Two articles described hyaluronic
      acid injection techniques. The total injected volume of hyaluronic acid ranged
      from 2 to 6 mL per session. Three articles used surgical techniques for labia
      majora augmentation. All included articles did not report any major or life
      threatening complications. All techniques demonstrated high satisfaction rates.
      Conclusions: Labia majora augmentation appears to be a safe, efficient technique
      with a high satisfaction rate and no reported major complications. However,
      further randomized controlled trials are warranted. Level of Evidence: 4.

PMID- 28449125
TI  - Saccharomyces cerevisiae accumulates GAPDH-derived peptides on its cell surface
      that induce death of non-Saccharomyces yeasts by cell-to-cell contact.
AB  - During wine fermentations, Saccharomyces cerevisiae starts to excrete
      antimicrobial peptides (AMPs) into the growth medium that induce death of non
      Saccharomyces yeasts at the end of exponential growth phase (24-48 h). Those AMPs
      were found to derive from the glycolytic enzyme glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH). On the other hand, the early death of non-Saccharomyces
      yeasts during wine fermentations was also found to be mediated by a cell-to-cell
      contact mechanism. Since GAPDH is a cell-wall-associated protein in S.
      cerevisiae, we put forward the hypothesis that the GAPDH-derived AMPs could
      accumulate on the cell surface of S. cerevisiae, thus inducing death of non
      Saccharomyces yeasts by cell-to-cell contact. Here we show that 48-h grown
      (stationary phase) cells of S. cerevisiae induce death of Hanseniaspora
      guilliermondii and Lachancea thermotolerans by direct cell-to-cell contact, while
      12-h grown cells (mid-exponential phase) do not. Immunological tests performed
      with a specific polyclonal antibody against the GAPDH-derived AMPs revealed their
      presence in the cell wall of S. cerevisiae cells grown for 48 h, but not for 12
      h. Taken together, our data show that accumulation of GAPDH-derived AMPs on the
      cell surface of S. cerevisiae is one of the factors underlying death of non
      Saccharomyces yeasts by cell-to-cell contact.

PMID- 28449126
TI  - Results of the ANSWER Trial Using the PulseRider for the Treatment of Broad
      Necked, Bifurcation Aneurysms.
AB  - BACKGROUND: The safety and probable benefit of the PulseRider (Pulsar Vascular,
      Los Gatos, California) for the treatment of broad-necked, bifurcation aneurysms
      was studied in the context of the prospective, nonrandomized, single arm clinical
      trial-the Adjunctive Neurovascular Support of Wide-neck aneurysm Embolization and
      Reconstruction (ANSWER) Trial. OBJECTIVE: To present the results of the United
      States cases employing the PulseRider device as part of the ANSWER clinical
      trial. METHODS: Aneurysms treated with the PulseRider device among sites
      enrolling in the ANSWER trial were prospectively studied and the results are
      summarized. Aneurysms arising at either the carotid terminus or basilar apex that
      were relatively broad necked were considered candidates for inclusion into the
      ANSWER study. RESULTS: Thirty-four patients were enrolled (29 female and 5 male)
      with a mean age of 60.9 years (27 basilar apex and 7 carotid terminus). Mean
      aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range
      2.3-11.6 mm). In all patients, the device was delivered and deployed. Immediate
      Raymond I or II occlusion was achieved in 82.4% and progressed to 87.9% at 6
      month follow-up. A modified Rankin Score of 2 or less was seen in 94% of patients
      at 6 months. CONCLUSION: The results from the ANSWER trial demonstrate that the
      PulseRider device is safe and offers probable benefit as for the treatment of
      bifurcation aneurysms arising at the basilar apex or carotid terminus. As such,
      it represents a useful addition to the armamentarium of the neuroendovascular
      specialist.

PMID- 28449127
TI  - Effects of emotional valence and arousal on the voice perception network.
AB  - Several theories conceptualise emotions along two main dimensions: valence (a
      continuum from negative to positive) and arousal (a continuum that varies from
      low to high). These dimensions are typically treated as independent in many
      neuroimaging experiments, yet recent behavioural findings suggest that they are
      actually interdependent. This result has impact on neuroimaging design, analysis
      and theoretical development. We were interested in determining the extent of this
      interdependence both behaviourally and neuroanatomically, as well as teasing
      apart any activation that is specific to each dimension. While we found extensive
      overlap in activation for each dimension in traditional emotion areas (bilateral
      insulae, orbitofrontal cortex, amygdalae), we also found activation specific to
      each dimension with characteristic relationships between modulations of these
      dimensions and BOLD signal change. Increases in arousal ratings were related to
      increased activations predominantly in voice-sensitive cortices after variance
      explained by valence had been removed. In contrast, emotions of extreme valence
      were related to increased activations in bilateral voice-sensitive cortices,
      hippocampi, anterior and midcingulum and medial orbito- and superior frontal
      regions after variance explained by arousal had been accounted for. Our results
      therefore do not support a complete segregation of brain structures underpinning
      the processing of affective dimensions.

PMID- 28449128
TI  - Comprehensive Ryan White Assistance and Human Immunodeficiency Virus Clinical
      Outcomes: Retention in Care and Viral Suppression in a Medicaid Nonexpansion
      State.
AB  - Background: Knowledge gaps remain about how the Ryan White human immunodeficiency
      virus (HIV)/AIDS Program (RW) contributes to health outcomes. We examined the
      association between different RW service classes and retention in care (RiC) or
      viral suppression (VS). Methods: We identified Virginians engaged in any HIV care
      between 1 January and 31 December 2014. RW beneficiaries were classified by
      receipt of >=1 service from 3 classes: Core medical, Support, and insurance
      and/or direct medication assistance through the AIDS Drug Assistance Program
      (ADAP). Receipt of all RW classes was defined as comprehensive assistance. We
      used multivariable logistic regression to compare the odds of RiC and of VS by
      comprehensive assistance and by RW classes alone and in combination. Results:
      Among 13104 individuals, 58% received any RW service and 17% comprehensive
      assistance. Comprehensive assistance is significantly associated with RiC
      (adjusted odds ratio [aOR], 8.8 [95% confidence interval {CI}, 7.2-10.8]) and
      viral suppression (aOR, 3.3 [95% CI, 2.9-3.8]). Receiving any 2 RW classes or
      Core alone is significantly associated with RiC and VS, with the strength of
      association decreasing as the number of classes decreases. Recipients of Support
      alone are significantly less likely to have VS (aOR, 0.75 [95% CI, .59-.96]). For
      ADAP recipients also receiving Core and/or Support, insurance assistance is
      significantly associated with VS compared to receiving direct medication only
      (aOR, 1.6 [95% CI, 1.3-1.9]); this relationship is not significant for those who
      receive ADAP alone. Conclusions: Receiving more classes of RW-funded services is
      associated with improved HIV outcomes. For some populations with insurance, RW
      funded services may still be required for optimal health outcomes.

PMID- 28449130
TI  - Reappraisal and new observations on atrial tachycardia ablated from the non
      coronary aortic sinus of Valsalva: authors' reply.

PMID- 28449129
TI  - Phenotypic differences determine drought stress responses in ecotypes of Arundo
      donax adapted to different environments.
AB  - Arundo donax has been identified as an important biomass and biofuel crop. Yet,
      there has been little research on photosynthetic and metabolic traits, which
      sustain the high productivity of A. donax under drought conditions. This study
      determined phenotypic differences between two A. donax ecotypes coming from
      stands with contrasting adaptation to dry climate. We hypothesized that the
      Bulgarian (BG) ecotype, adapted to drier conditions, exhibits greater drought
      tolerance than the Italian (IT) ecotype, adapted to a more mesic environment.
      Under well-watered conditions the BG ecotype was characterized by higher
      photosynthesis, mesophyll conductance, intrinsic water use efficiency, PSII
      efficiency, isoprene emission rate and carotenoids, whereas the IT ecotype showed
      higher levels of hydroxycinnamates. Photosynthesis of water-stressed plants was
      mainly limited by diffusional resistance to CO2 in BG, and by biochemistry in IT.
      Recovery of photosynthesis was more rapid and complete in BG than in IT, which
      may indicate better stability of the photosynthetic apparatus associated to
      enhanced induction of volatile and non-volatile isoprenoids and phenylpropanoid
      biosynthesis. This study shows that a large phenotypic plasticity among A. donax
      ecotypes exists, and may be exploited to compensate for the low genetic
      variability of this species when selecting plant productivity in constrained
      environments.

PMID- 28449131
TI  - Erratum.

PMID- 28449132
TI  - Sex and Diffusion Tensor Imaging of White Matter in Schizophrenia: A Systematic
      Review Plus Meta-analysis of the Corpus Callosum.
AB  - Sex is considered an understudied variable in health research. Schizophrenia is a
      brain disorder with known sex differences in epidemiology and clinical
      presentation. We systematically reviewed the literature for sex-based differences
      of diffusion properties of white matter tracts in schizophrenia. We then
      conducted a meta-analysis examining sex-based differences in the genu and
      splenium of the corpus callosum in schizophrenia. Medline and Embase were
      searched to identify relevant papers. Studies fulfilling the following criteria
      were included: (1) included individuals with a diagnosis of schizophrenia, (2)
      included a control group of healthy individuals, (3) included both sexes in the
      patient and the control groups, (4) used diffusion tensor imaging, and (5)
      involved analyzing metrics of white matter microstructural integrity. Fractional
      anisotropy (FA) was used as the measure of interest in the meta-analysis. Of 730
      studies reviewed, 75 met the inclusion criteria. Most showed no effect of sex,
      however, those that did found either that females have lower FA than males, or
      that the effect of disease in females is larger than that in males. The findings
      of the meta-analysis in the corpus callosum supported this result. There is a
      recognized need for studies on schizophrenia with a sufficient sample of female
      patients. Lack of power undermines the ability to detect sex-based differences.
      Understanding the sex-specific impact of illness on neural circuits may help
      inform development of new treatments, and improvement of existing interventions.

PMID- 28449135
TI  - Friendship and Depression Among Couples in Later Life: The Moderating Effects of
      Marital Quality.
AB  - Objectives: The aims of the study were to examine within-person associations
      between social interactions with friends (one's own and partner's) and depressive
      symptoms over time among couples in later life and to investigate whether marital
      quality moderated the associations. Methods: We used longitudinal data from the
      Health and Retirement Study (2004-2012) to examine a sample of coupled
      individuals (dyad N = 6,833). Dyadic growth curve models were employed to test
      the study hypotheses. Results: Results indicated that more frequent social
      interactions with friends were associated with fewer depressive symptoms of
      individuals and there were cross-spousal effects for this association. Further,
      marital quality moderated the within-person association between social
      interaction with friends and depressive symptoms such that the association was
      stronger for individuals experiencing poor marital quality compared to those with
      better marital quality. Discussion: Friendship is an important contributor to
      individuals' mental health in later life, with its benefits having far-reaching
      consequences for one's significant other. The implications of friendship
      interactions for other health domains also require investigation within the
      marital context.

PMID- 28449133
TI  - Maternal alcohol use during pregnancy and offspring attention-deficit
      hyperactivity disorder (ADHD): a prospective sibling control study.
AB  - Background: Maternal alcohol use during pregnancy has repeatedly been associated
      with development of attention-deficit hyperactivity disorder (ADHD) in the
      offspring. It is, however not known whether this reflects a direct casual intra
      uterine effect or a non-causal relationship due to confounding. We used three
      different approaches to control for measured and unmeasured confounding:
      statistical adjustment for covariates, negative control comparison against
      maternal pre-pregnancy alcohol use, and comparison among differentially exposed
      siblings. Methods: The sample comprised 114 247 children (34 283 siblings) from
      94 907 mothers, recruited to the Norwegian Mother and Child Birth Cohort Study
      between 1999 and 2008. Self-reported measurements of alcohol use were obtained in
      week 30 during the pregnancy. Mothers rated offspring ADHD symptoms at 5 years on
      two measures. Clinical ADHD diagnoses were obtained from the Norwegian Patient
      Registry. Results: We found an overall positive association between maternal
      alcohol use during pregnancy and offspring ADHD symptoms, which was only
      marginally attenuated after inclusion of measured covariates. Both the negative
      control and the sibling comparison analysis further attenuated the estimated
      association, but it remained greater than zero [beta = 0.017, 95% confidence
      interval (CI) = 0.005-0.030). No association was found between maternal alcohol
      use during pregnancy and offspring ADHD diagnosis. Conclusions: For offspring
      ADHD symptoms we found a weak, but possibly causal association with maternal
      alcohol use during pregnancy, but no such effect was observed for clinical ADHD
      diagnosis.

PMID- 28449134
TI  - Characterizing exogenous mRNA delivery, trafficking, cytoplasmic release and RNA
      protein correlations at the level of single cells.
AB  - The use of synthetic messenger ribonucleic acid (mRNA) to express specific
      proteins is a highly promising therapeutic and vaccine approach that avoids many
      safety issues associated with viral or DNA-based systems. However, in order to
      optimize mRNA designs and delivery, technology advancements are required to study
      fundamental mechanisms of mRNA uptake and localization at the single-cell and
      tissue level. Here, we present a single RNA sensitive fluorescent labeling method
      which allows us to label and visualize synthetic mRNA without significantly
      affecting function. This approach enabled single cell characterization of mRNA
      uptake and release kinetics from endocytic compartments, the measurement of
      mRNA/protein correlations, and motivated the investigation of mRNA induced
      cellular stress, all important mechanisms influencing protein production. In
      addition, we demonstrated this approach can facilitate near-infrared imaging of
      mRNA localization in vivo and in ex-vivo tissue sections, which will facilitate
      mRNA trafficking studies in pre-clinical models. Overall, we demonstrate the
      ability to study fundamental mechanisms necessary to optimize delivery and
      therapeutic strategies, in order to design the next generation of novel mRNA
      therapeutics and vaccines.

PMID- 28449137
TI  - Video Comment on Jin Min Cho et al.

PMID- 28449136
TI  - [Alpha-2 Macroglobulin Serum Level in Patients with Alpha-1 Antitrypsin
      Deficiency].
AB  - Background and objectives Alpha-2 Macroglobulin (A2M) is a plasma protein with
      proteolytic effects on many proteases. In patients with an inborn alpha-1
      antitrypsin deficiency (AATD) the homeostasis between proteases and antiproteases
      is disturbed. The aim of this study was to compare the levels of AAT and A2 M in
      patients and controls. We hypothesized that in patients with AATD A2 M levels are
      elevated. Methods Patients with AATD (polymorphism Pi*ZZ, Pi*SZ, Pi*MZ and rare
      gene variants) as well as healthy volunteers (Pi*MM) were tested for A2 M and AAT
      levels. The concentration of the proteins was measured by nephelometry. The
      polymorphisms Pi*Z and Pi*S were detected by polymerase chain reaction (PCR), the
      rare genetic variants were identified by sequencing. Results In our study, a
      total of 291 individuals were included. It could be shown that a significant
      increase in A2 M levels in the serum could be observed in the presence of a gene
      polymorphism (Pi*ZZ) and an alpha-1 antitrypsin serum level < 50 mg/dl compared
      to the healthy volunteers. Conclusions In this study, an inverse correlation
      between the serum levels of AAT and A2 M was found in the presence of a gene
      polymorphism (Pi*ZZ). Further studies are necessary to elucidate the clinical
      significance of increased A2 M serum levels in patients with severe AAT
      deficiency Pi*ZZ and rare gene variants whose AAT serum level is < 50 mg/dl.

PMID- 28449138
TI  - Video Comment on Sergio Cadoni et al.

PMID- 28449139
TI  - Video Comment on Ioannis S. Papanikolaou et al.

PMID- 28449140
TI  - Video Comment on Philipp-Alexander Neumann et al.

PMID- 28449141
TI  - Endoscopic sphincterotomy in pediatric patients: do we know enough?

PMID- 28449142
TI  - Adenoma detection rate - is it all about adding water?

PMID- 28449143
TI  - Selection bias complicates comparisons of endoscopic submucosal dissection vs.
      endoscopic mucosal resection in the treatment of colorectal neoplasms.

PMID- 28449144
TI  - Reply to Kanesaka et al.

PMID- 28449147
TI  - French comment on article Evaluation of narrow-band imaging signs in eosinophilic
      and lymphocytic esophagitis.

PMID- 28449148
TI  - French comment on article Early adverse events and long-term outcomes of
      endoscopic sphincterotomy in a pediatric population: a single-center experience.

PMID- 28449149
TI  - French comment on article Extracorporeal shock wave lithotripsy is safe and
      effective for pediatric patients with chronic pancreatitis.

PMID- 28449150
TI  - French comment on article Water exchange for screening colonoscopy increases
      adenoma detection rate: a multicenter, double-blinded, randomized controlled
      trial.

PMID- 28449151
TI  - French comment on article Laparoscopic and luminal endoscopic cooperative surgery
      can be a standard treatment for submucosal tumors of the stomach: a retrospective
      multicenter study.

PMID- 28449152
TI  - French comment on article Lower adenoma miss rate with FUSE vs. conventional
      colonoscopy with proximal retroflexion: a randomized back-to-back trial.

PMID- 28449153
TI  - French comment on article Long-term outcome of endoscopic ultrasound-guided
      pelvic abscess drainage: a two-center series.

PMID- 28449154
TI  - Dual RAAS Blockade with Aliskiren in Patients with Severely Impaired Chronic
      Kidney Disease.
AB  - Dual renin-angiotensin-aldosterone blockade (dRAASb) is purposed in the
      prevention of the cardiorenal syndrome (CRS). However, all attempts with dRAASb
      even in patients with moderate impaired chronic kidney disease (CKD) were
      terminated due to the typical severe adverse events (SAE), e. g., hyperkalemia
      and rise of serum creatinine. The aim of our study with the direct renin
      inhibitor aliskiren was to evaluate the effect of dRAASb with a washout phase in
      patients with severely advanced CKD. We have studied 45 patients (G3b to 4, A2
      and >A3; median glomerular filtration rate (GFR) CKD-EPI 31 (23-40) ml/min per
      1.73 m2 BSA (body surface area), albumin-creatinine-ratio in urine (UACR) (0.413
      (0.164 to 1.39) g/g) and proteinuria (0.5 (0.2 to 0.9) g/l) before, with and
      without aliskiren (150 respectively 300 mg per day) added to an angiotensin
      converting enzyme inhibitor (ACEi) or an AT1-receptor blocker (ARB) over 4 1/2
      years. The dRAASb with aliskiren showed a significant decrease of proteinuria
      (0.5 to 0.38 g/l), especially in patients with an UACR>=350 mg/g and in the
      subgroup analysis e. g., in patients with diabetes, but proteinuria increased in
      the washout phase again. The blood pressure (130/80 mm Hg), serum potassium (4.9
      to 5.0 mmol/l) and GFR remained nearly constant (31 to 29.5 ml/min per 1.73 m2
      BSA). A more than 30% increase in serum creatinine was associated with an
      UACR>300 mg/g. The dRAASb has beneficial effects on proteinuria and is safe in
      patients with severely advanced CKD. However, in patients with high UACR (>300
      mg/g) raise of creatinine and potassium have to be controlled.

PMID- 28449155
TI  - Mitochondrial Dysfunction in Diabetic Cardiomyopathy: Effect of Mesenchymal Stem
      Cell with PPAR-gamma Agonist or Exendin-4.
AB  - Therapy targeting mitochondria may provide novel ways to treat diabetes and its
      complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome
      proliferator-activated receptor gamma (PPAR-gamma) agonists and exendin-4; an
      analog of glucagon-like peptide-1 have shown cardioprotective properties in many
      cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy
      (DCM) in relation to mitochondrial dysfunction. This work included seven groups
      of adult male albino rats: the control group, the non-treated diabetic group, and
      the treated diabetic groups: one group was treated with MSCs only, the second
      with pioglitazone only, the third with MSCs and pioglitazone, the forth with
      exendin-4 only and the fifth with MSCs and exendin-4. All treatments were started
      after 6 weeks from induction of diabetes and continued for the next 4 weeks.
      Blood samples were collected for assessment of glucose, insulin, and cardiac
      enzymes. Hearts were removed and used for isolated heart studies, and gene
      expression of: myocyte enhancer factor-2 (Mef2), peroxisome proliferator
      activated receptor gamma coactivator1-alpha (PGC1alpha), nuclear factor kappa B
      (NFKB) and autophagic markers: light chain 3 (LC3) and beclin by real-time
      reverse transcription-polymerase chain reaction. The cardiac mitochondrial
      protein levels of cardiolipin and uncoupler protein 2 (UCP2) were assessed by
      ELISA and western blot technique, respectively. Treated groups showed significant
      improvement in left ventricular function associated with improvement in the
      cardiac injury and myopathic markers compared to the non treated diabetic group.
      NFKB was down-regulated while cardiolipin, PGC1alpha, LC.3 and beclin were up
      regulated in all treated groups. These data suggest that the cardioprotective
      effects of MSCs, exendin-4 or pioglitazone based on their ability to improve
      mitochondrial functions through targeting inflammatory and autophagy signaling.
      The co- administration of pioglitazone or exendin-4 with MSCs showed significant
      superior improvement compared with MSCs alone, indicating the ability to use them
      in supporting cardioprotective effects of MSCs.

PMID- 28449156
TI  - Development of Multiple-Unit Floating Drug Delivery System of Clarithromycin:
      Formulation, in vitro Dissolution by Modified Dissolution Apparatus, in vivo
      Radiographic Studies in Human Volunteers.
AB  - Clarithromycin (CM), a broad spectrum macrolide antibiotic used to eradicate H.
      pylori in peptic ulcer. Clarithromycin (CM) is well absorbed from the
      gastrointestinal tract, but has a bioavailability of 50% due to rapid
      biodegradation. The aim of this investigation was to increase the gastric
      residence time, and to control the drug release of clarithromycin by formulating
      into multiple unit floating mini-tablets. Floating tablets were prepared by using
      direct compression method with HPMC K4M and Polyox WSR 1105 as release retarded
      polymers and sodium bicarbonate as gas generating agent. The prepared mini
      tablets were evaluated for thickness, weight variation, friability, hardness,
      drug content, in vitro buoyancy, swelling studies, in vitro dissolution studies
      by using modified Rossett-Rice test and in vivo radiographic studies in healthy
      human volunteers in fasting conditions. DSC analysis revealed that no interaction
      between drug and excipients. All the physical parameters of the tablets were
      within the acceptable limits. The optimized formulation (F6) had showed
      controlled drug release of 99.16+/-3.22% in 12 h, by zero-order release kinetics,
      along with floating lag time of 9.5+/-1.28 s and total floating time of 12+/-0.14
      h. X-ray imaging studies revealed that in vivo gastric residence time of
      clarithromycin floating mini-tablet in the stomach was about 3.5 h. The results
      demonstrated that the developed floating mini-tablets of clarithromycin caused
      significant enhancement in gastric retention time along with sustained effect and
      increased oral bioavailability.

PMID- 28449157
TI  - [Causes and Relevance of Intramural and Intravascular Air].

PMID- 28449168
TI  - MRI Sequences in Head & Neck Radiology - State of the Art.
AB  - Background Magnetic resonance imaging (MRI) has become an essential imaging
      modality for the evaluation of head & neck pathologies. However, the diagnostic
      power of MRI is strongly related to the appropriate selection and interpretation
      of imaging protocols and sequences. The aim of this article is to review state-of
      the-art sequences for the clinical routine in head & neck MRI and to describe the
      evidence for which medical question these sequences and techniques are useful.
      Method Literature review of state-of-the-art sequences in head & neck MRI.
      Results and Conclusion Basic sequences (T1w, T2w, T1wC+) and fat suppression
      techniques (TIRM/STIR, Dixon, Spectral Fat sat) are important tools in the
      diagnostic workup of inflammation, congenital lesions and tumors including
      staging. Additional sequences (SSFP (CISS, FIESTA), SPACE, VISTA, 3D-FLAIR) are
      used for pathologies of the cranial nerves, labyrinth and evaluation of
      endolymphatic hydrops in Meniere's disease. Vessel and perfusion sequences (3D
      TOF, TWIST/TRICKS angiography, DCE) are used in vascular contact syndromes,
      vascular malformations and analysis of microvascular parameters of tissue
      perfusion. Diffusion-weighted imaging (EPI-DWI, non-EPI-DWI, RESOLVE) is helpful
      in cholesteatoma imaging, estimation of malignancy, and evaluation of treatment
      response and posttreatment recurrence in head & neck cancer. Understanding of MRI
      sequences and close collaboration with referring physicians improves the
      diagnostic confidence of MRI in the daily routine and drives further research in
      this fascinating image modality. Key Points:  . Understanding of MRI sequences is
      essential for the correct and reliable interpretation of MRI findings.. . MRI
      protocols have to be carefully selected based on relevant clinical information..
      . Close collaboration with referring physicians improves the output obtained from
      the diagnostic possibilities of MRI.. Citation Format . Widmann G, Henninger B,
      Kremser C et al. MRI Sequences in Head & Neck Radiology - State of the Art.
      Fortschr Rontgenstr 2017; 189: 413 - 422.

PMID- 28449169
TI  - Analysis of Liver Tumors Using Preoperative and Intraoperative Contrast-Enhanced
      Ultrasound (CEUS/IOCEUS) by Radiologists in Comparison to Magnetic Resonance
      Imaging and Histopathology.
AB  - Purpose To evaluate the diagnostic significance of preoperatively and
      intraoperatively performed contrast-enhanced ultrasound (CEUS/IOCEUS) in the
      diagnosis of liver tumors in comparison to magnetic resonance imaging (MRI) and
      histopathology. Materials and Methods Retrospective analysis of 70/317 patients
      who underwent surgery for liver tumors between January 2012 and October 2015.
      Findings of CEUS and IOCEUS were compared to MRI. CEUS and IOCEUS were performed
      using multifrequency linear probes (1 - 5, 6 - 15 MHz) after bolus injection of 1
      - 5 ml sulfur hexafluoride microbubbles. The histopathology after surgical
      resection, MRI morphology (T1, T2, VIBE, diffusion sequences) and wash-in/wash
      out kinetics of CEUS were evaluated. Results In 70 analyzed patient cases, 64
      malignant liver lesions could be detected. 6 patients had benign liver lesions.
      Among the 64 malignant lesions, there were 28 metastases, 24 hepatocellular
      carcinomas (HCC), 9 cholangiocellular carcinomas (CCC) and 3 gallbladder
      carcinomas. 2 of the 6 benign liver lesions were hemangiomas, 2 were adenomas, 1
      was an FNH and 1 was a complicated cyst. There was no significant difference when
      determining the lesion's malignancy/ benignity (p = 1.000). Furthermore, there
      was no statistical significance between preoperative CEUS and MRI regarding the
      general differential diagnosis of a tumor (p = 0.210) and the differential
      diagnosis classification between HCCs (p = 0.453) and metastases (p = 0.250).
      There was no statistical significance in tumor size (10 mm - 151 mm; mean 49 mm
      SD +/- 31 mm) and location (tumor size p = 0.579; allocation to liver lobes p =
      0.132; segment diagnosis p = 0.121) between preoperatively performed CEUS and
      MRI. The combination of preoperative MRI and CEUS for lesion detection showed
      significant differences compared to CEUS or MRI only (p < 0.001 for CEUS; p =
      0.004 for MRI). IOCEUS offered the substantial advantage of locating additional
      liver lesions (p = 0.004 compared to preoperative MRI, p = 0.002 compared to
      preoperative CEUS). In 10/37 cases (27 %) IOCEUS could locate further liver
      lesions which had not been identified during CEUS and/or MRI preoperatively, so
      that operative therapy was adapted accordingly and resection was extended if
      necessary. Conclusion CEUS proves to be a dynamic imaging method for preoperative
      diagnosis of liver tumors showing high diagnostic significance in the
      characterization of a tumor's microvascularization, its entity and its size.
      During liver operations CEUS plays an important role in surgical therapy
      decisions. Citation Format . Huf S, Platz Batista da Silva N, Wiesinger I et al.
      Analyse von Lebertumorentitaten mittels praoperativer und intraoperativer
      Kontrastmittelsonografie (CEUS/IOCEUS) durch Radiologen im Vergleich zur
      Magnetresonanztomografie und zur Histopathologie. Fortschr Rontgenstr 2017; 189:
      431 - 440.

PMID- 28449170
TI  - ?

PMID- 28449181
TI  - Metabolite Profile and Antiproliferative Effects in HaCaT Cells of a Salix
      reticulata Extract.
AB  - Phenolic constituents of Salix reticulata (Salicaceae) and antiproliferative
      activity of an extract and individual compounds were investigated in immortalized
      human non-tumorigenic keratinocytes (HaCaT). A MeOH extract from aerial parts
      afforded several flavonoids, including luteolin and apigenin glycosides (2-5 and
      9) and catechin (1), two procyanidin fractions, and the phenolic glucosides
      picein (6), triandrin (7), and salicortin (8). In an adenosine triphosphate
      assay, the MeOH extract reduced cell viability by approximately 60 % at a
      concentration of 100 ug/mL. Cell proliferation was assessed with a BrdU
      incorporation ELISA assay. The extract inhibited proliferation of HaCaT cells in
      a concentration-dependent manner, with approximately 50 % inhibition at 100
      ug/mL. In time-lapse assays, the extract showed distinct inhibitory effects on
      cell migration at concentrations of 12.5, 25, and 50 ug/mL. The activity of
      selected constituents was also determined. Luteolin-7-O-beta-glucuronide (3)
      significantly inhibited cell proliferation at concentrations of 10 and 50 uM. In
      contrast, luteolin-7-O-beta-glucopyranoside (2) and a procyanidin fraction (P1)
      had only weak effects, while picein (6) and salicortin (8) did not affect cell
      proliferation. Luteolin-7-O-beta-glucuronide (10 uM) and, to a lesser extent, the
      procyanidin fraction (10 ug/mL) also inhibited cell migration.

PMID- 28449183
TI  - Noninferiority trial investigating the efficacy of a nonantibiotic intramammary
      therapy in the treatment of mild-to-moderate clinical mastitis in dairy cows with
      longer lasting udder diseases.
AB  - A nonblinded, positively controlled, noninferiority trial was conducted to
      evaluate the efficacy of an alternative, nonantibiotic therapy with Masti
      Veyxym(r) to reduce ineffective antibiotic usage in the treatment of nonsevere
      clinical mastitis (CM) in cows with longer lasting udder diseases. The solely
      intramammary treatment with Masti Veyxym(r) (three applications, 12 hr apart) and
      the combined treatment with Masti Veyxym(r) and antibiotics as usual on the farm
      according to label of the respective product were compared with the reference
      treatment of solely antibiotic therapy. The matched field study was conducted on
      eight free-stall dairy farms located in Eastern Germany. Cases of mild-to
      moderate CM in cows with longer lasting high somatic cell counts in preceding
      dairy herd improvement test days and with previous CM cases in current lactation
      were randomly allocated to one of the three treatment groups. A foremilk sample
      of the affected quarter was taken before treatment and again approximately 14
      days and 21 days after the end of therapy for cyto-bacteriological examination.
      Primary outcomes were clinical cure (CC) and no CM recurrence within 60 days
      after the end of treatment (no R60). Bacteriological cure (BC) and quarter
      somatic cell count (QSCC) cure were chosen as secondary outcomes although low
      probabilities of BC and QSCC cure for selected cows were expected. The study
      resulted in the following findings: the pathogens mostly cultured from
      pretreatment samples were Streptococcus uberis, followed by Staphylococcus aureus
      and coagulase-negative staphylococci. There were no significant differences
      between the two test treatments in comparison with the reference treatment
      regarding all outcome variables. The sole therapy with Masti Veyxym(r) resulted
      in a numerically lower likelihood of BC without significant differences to the
      reference treatment. The combined therapy group showed a numerically higher
      nonrecurrence rate than the two other treatment groups and noninferiority
      compared to the reference treatment was proven. Having regard to the selection
      criteria of cows in this study, the findings indicated that sole treatment with
      Masti Veyxym(r) in nonsevere CM cases may constitute an alternative therapy to
      reduce antibiotics. However, noninferiority evaluations were mostly inconclusive.
      Further investigations with a larger sample size are required to confirm the
      results and to make a clear statement on noninferiority.

PMID- 28449182
TI  - Validation of a nomogram for selecting patients for chemotherapy after D2
      gastrectomy for cancer.
AB  - BACKGROUND: According to some guidelines for the management of gastric cancer,
      adjuvant chemotherapy is recommended for patients with pT3-4 or node-positive
      disease. The aim of this study was to define low- and high-risk groups in terms
      of survival, and to predict the benefit of adjuvant fluoropyrimidine plus
      oxaliplatin (F-OX) chemotherapy. METHODS: Patients with pT3-4 or node-positive
      gastric cancer after gastrectomy with D2 lymphadenectomy between 2000 and 2013
      were included. The performance of a previously published nomogram was assessed by
      discrimination and calibration. Patients were stratified into risk groups on the
      basis of the nomogram-predicted overall survival probability. The efficacy of F
      OX within each risk subgroup was assessed using the log rank test and Cox
      regression analysis weighted by inverse propensity score. RESULTS: Some 1464
      patients were included. The nomogram showed better discrimination than the
      seventh AJCC staging classification (concordance index 0.72 versus 0.68
      respectively; P = 0.008) and accurate calibration. F-OX was not associated with
      improved survival in patients in the low-risk group, whereas it reduced the risk
      of death by over 20 per cent in the intermediate- and high-risk groups (P = 0.036
      and P < 0.001 respectively) (P for interaction = 0.014). CONCLUSION: A nomogram
      can aid in individualized decision-making regarding the administration of F-OX
      after gastrectomy for cancer.

PMID- 28449184
TI  - Dermoscopy use by Canadian dermatologists and dermatology residents: a cross
      sectional nationwide study.

PMID- 28449185
TI  - Effect of oil and shortening in rice bread quality: Relationship between dough
      rheology and quality characteristics.
AB  - : One of the main problems with gluten-free breads is their texture and their
      rapid staling. Fats are widely used for the improvement of texture and other
      quality parameters in gluten-free breads. The effect of oil and shortening in
      rice-breads quality and its correlation with dough rheology has been analyzed.
      The inclusion of oil increased the specific volume of the breads and reduced
      their hardness, particularly with lower levels of hydration, whereas shortening
      did not modify specific volume or reduced it when hydration levels were higher.
      Oil, at levels of up to 30%, reduced the cohesiveness, springiness and resilience
      of breads, as well as the brightness of the crust, and increased the a* and b*
      values. Breads with oil also exhibited a greater number of pores per cm2 ,
      especially in doughs with higher levels of hydration. An inverse correlation
      between G' and G'' and bread specific volume has been observed, being the
      reciprocal-Y model a better predictor than the linear model to relate the bread
      specific volume. PRACTICAL APPLICATIONS: This study showed that the type and
      quantity of fat added in rice based breads affect the bread quality in a
      different way. In general, it can be said that the incorporation of up to 20% oil
      improved rice based breads. Oil increased the specific volume, the a* and b*
      parameters of the crust and the cell density. It also decreases hardness,
      cohesiveness, springiness, resilience, and the L* parameter. Converse to breads
      made with oil, the addition of shortening can negatively affect the quality of
      the breads. Moreover, the correlation analysis has demonstrated that the study of
      dough rheology could be a good predictor of gluten-free bread quality.

PMID- 28449186
TI  - The risk of lower gastrointestinal bleeding in low-dose aspirin users.
AB  - BACKGROUND: Aspirin increases the risk of gastrointestinal bleeding. AIM: To
      investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
      METHODS: Low-dose (75-325 mg daily) aspirin users and controls matched by age,
      gender and enrollment time in a 1:5 ratio were selected from 1 million randomly
      sampled subjects in the National Health Insurance Research Database of Taiwan.
      Cox proportional hazard regression models were developed to evaluate the
      predictors of LGIB with adjustments for age, gender, comorbidities including
      coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney
      disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia,
      uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and
      concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti
      inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump
      inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates,
      alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel
      blockers. RESULTS: A total of 53 805 aspirin users and 269 025 controls were
      included. Aspirin group had a higher incidence of LGIB within 1 year than control
      group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio [HR]: 2.75, 95% confidence
      interval [CI]: 2.06-3.65), NSAIDs (HR: 8.61, 95% CI: 3.28-22.58), steroids (HR:
      10.50, 95% CI: 1.98-55.57), SSRIs (HR: 11.71, 95% CI: 1.40-97.94), PPIs (HR:
      8.47, 95% CI: 2.26-31.71), and H2RAs (HR: 10.83, 95% CI: 2.98-39.33) were
      significantly associated with LGIB. CONCLUSIONS: The risk of LGIB was higher in
      low-dose aspirin users than in aspirin nonusers in this nationwide cohort. Low
      dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk
      factors for LGIB.

PMID- 28449187
TI  - Distinctive clinical characteristics and favorable outcomes in patients with
      large granular lymphocytosis after allo-HCT: 12-year follow-up data.
AB  - An increase in large granular lymphocytes (LGL) is frequently seen in patients
      following allogeneic hematopoietic cell transplantation (allo-HCT) and it has
      been associated with better outcomes in some reports. We assessed 826 consecutive
      patients at our institution with over 12 years of follow-up for the occurrence of
      LGL lymphocytosis after allo-HCT. The 3-year cumulative incidence of LGL
      lymphocytosis was 14.5% with a median duration of over 3.5 years. The development
      of LGL lymphocytosis was strongly correlated with CMV viremia and GVHD. The
      clinical course of patients with LGL lymphocytosis after allo-HCT was indolent,
      with the majority of these patients not displaying any clinical signs or symptoms
      related to the LGL proliferation. LGL lymphocytosis was associated with better
      outcomes, including higher overall survival (OS 86.6% vs 44.7% at 3 years), lower
      non-relapse mortality (NRM 5.5% vs 30.4% at 3 years), and lower risk of relapse
      (8.9% vs 22.9% at 3 years). A time-dependent multivariable analysis confirmed the
      favorable impact of LGL lymphocytosis on OS and NRM, but not on the risk of
      relapse. In multivariable analysis, a longer duration of LGL lymphocytosis was
      associated with better OS and NRM. Improved immunomodulatory properties of these
      cells, regulating GVHD and infections, may explain the observed favorable
      outcomes of patients who developed LGL lymphocytosis following allo-HCT.

PMID- 28449189
TI  - Reply: adalimumab is a safe option for psoriasis patients with concomitant
      hepatitis B or C infection: a multicentre cohort study of 37 patients and review
      of the literature.

PMID- 28449188
TI  - Development, validation and testing of a skin sampling method for assessment of
      metal exposure.
AB  - BACKGROUND: Nickel, cobalt and chromium are frequent skin sensitizers. Skin
      exposure results in eczema in sensitized individuals, the risk being related to
      the skin dose. OBJECTIVES: To develop a self-sampling method for quantification
      of skin exposure to metals, to validate the method, and to assess its
      feasibility. METHODS: Defined metal doses (0.01-5 ug) were applied to the fingers
      of 5 participants. Skin areas (2 cm2 ) were sampled with 1% HNO3 , either as 0.1
      ml on a swab, or as 0.5 ml on a wipe. Furthermore, 17 participants performed self
      sampling by swab after 2 h of leisure activity. Samples were extracted in 1% HNO3
      and analysed by inductively coupled plasma mass spectrometry. RESULTS: The
      sampling efficiency by swab was 46%, as compared with 93% for acid wipe sampling,
      for all tested doses. Most metal from the skin dose was detected in the first
      swab (33-43%). Despite lower sampling efficiency by swab, skin doses of metals
      following 2 h of leisure activity without hand washing were quantified in all
      participants, and ranged from 0.0016 to 0.15 ug/cm2 , from 0.00014 to -0.0020
      ug/cm2 and from 0.00048 to -0.027 ug/cm2 for nickel, cobalt, and chromium,
      respectively. CONCLUSIONS: The results indicate a future potential of skin
      sampling by swab to detect and monitor metals on skin by self-sampling. This will
      contribute to better knowledge of metal skin exposure among dermatitis patients,
      workers, and the general population.

PMID- 28449190
TI  - Consensus statement on prevention and management of adverse effects following
      rejuvenation procedures with hyaluronic acid-based fillers.
AB  - Facial fillers play an important role in the correction of facial changes
      associated with ageing. They offer quick treatments in the outpatient setting
      with minimal subsequent downtime that provide predictable, natural-looking, long
      lasting results. Adverse reactions after hyaluronic acid injections tend to be
      mild or moderate and rather temporary. However, as with all injected or implanted
      biomaterials, severe adverse events can occur and patients must be fully informed
      of potential risks prior to undergoing treatment. A panel of experts from Germany
      (D), Austria (A) and Switzerland (CH) developed recommendations, and this study
      provides the 'DACH Consensus Recommendations' from this group specifically on the
      use of hyaluronic acid fillers. The aim is to help clinicians recognize potential
      risks and to provide guidance on how best to treat adverse events if they arise.
      Contraindications to hyaluronic acid fillers are also detailed, and ways to
      prevent adverse events occurring are discussed. Hyaluronic acid-based products
      are claimed to be very close to an ideal tissue augmentation agent; nevertheless,
      profound medical, anatomical and product knowledge are of paramount importance to
      minimize the occurrence of adverse reactions.

PMID- 28449192
TI  - Anti-Inflammatory Effects of PEGylated Human Adrenomedullin in a Mouse DSS
      Induced Colitis Model.
AB  - Preclinical Research Human adrenomedullin (hAM), a hypotensive peptide, also has
      anti-inflammatory effects. hAM can reduce the severity of the dextran sulphate
      sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in
      animal models. Furthermore, in a clinical study, hAM treatment reduced the
      Disease Activity Index in ulcerative colitis. However, these therapeutic effects
      required continuous administration of hAM as the half-life of native hAM is quite
      short in blood. To resolve this problem, hAM N-terminal was conjugated with two
      kinds of polyethylene glycol (PEG); 5 kDa PEG or 60 kDa PEG (5 kDa PEG-hAM and 60
      kDa PEG-hAM respectively). In a previous study, 5 kDa PEG-hAM stimulated cAMP
      production and prolonged the plasma half-life compared with native hAM. Herein we
      examine the effect of PEG-hAM in the DSS colitis model. Treatment with both PEG
      hAM preparations reduced the total inflammation score. In addition, the plasma
      half-life of 60 kDa PEG-hAM was much longer than 5 kDa PEG-hAM. In summary, a
      single subcutaneous administration of 60 kDa PEG-hAM reduced the total
      inflammation score in mice with DSS-induced colitis. Therefore, these results
      suggest that 60 kDa PEG-hAM is a possible therapeutic agent for the treatment of
      inflammatory bowel disease. Drug Dev Res 78 : 129-134, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28449191
TI  - Perceived harms and benefits of tobacco, marijuana, and electronic vaporizers
      among young adults in Colorado: implications for health education and research.
AB  - AIMS: To evaluate how young adults perceive and compare harms and benefits of
      marijuana and tobacco products in the context of a legal marijuana market in
      Colorado. DESIGN: Semi-structured qualitative interviews. SETTING: Denver, CO,
      USA. PARTICIPANTS: Thirty-two young adults (aged 18-26 years) who used
      tobacco/marijuana/vaporizers. MEASUREMENTS: Semi-structured interviews addressed
      perceived harms and benefits of various tobacco and marijuana products and
      personal experiences with these products. FINDINGS: Young adults evaluated harms
      and benefits using five dimensions: (1) combustion-smoking was considered more
      harmful than non-combustible products (e.g. e-cigarettes, vaporizers and
      edibles); (2) potency-edibles and marijuana concentrates were perceived as more
      harmful than smoking marijuana flower because of potential to receive too large a
      dose of tetrahydrocannabinol (THC); (3) chemicals-products containing chemical
      additives were seen as more harmful than 'pure' or 'natural' plant products; (4)
      addiction-participants recognized physiological addiction to nicotine, but talked
      primarily about psychological or life-style dependence on marijuana; and (5)
      source of knowledge-personal experiences, warning labels, campaigns, the media
      and opinions of product retailers and medical practitioners affected perceptions
      of harms and benefits. CONCLUSIONS: Among young adults in Colorado, USA,
      perceived harms and benefits of tobacco and marijuana include multiple
      dimensions. Health educational campaigns could benefit from addressing these
      dimensions, such as the potency of nicotine and cannabis concentrates and harmful
      chemicals present in the organic material of tobacco and marijuana. Descriptors
      such as 'natural' and 'pure' in the promotion or packaging of tobacco and
      marijuana products might be misleading.

PMID- 28449193
TI  - Impact of metformin on patients with advanced head and neck cancer undergoing
      concurrent chemoradiotherapy.
AB  - BACKGROUND: The purpose of this study was to evaluate the impact of metformin on
      toxicities and survival in patients with head and neck cancer undergoing
      concurrent chemoradiotherapy (CRT). METHODS: We retrospectively analyzed and
      compared the clinical characteristics, treatment tolerance, toxicities, and
      survival of 252 patients with stages III, IVA, and IVB head and neck cancer
      undergoing concurrent CRT with and without metformin treatment between 2007 and
      2010. RESULTS: Among all patients, 39 patients received metformin whereas 219
      patients did not. Both groups had similar clinical characteristics and nearly
      identical disease-free survival and overall survival. However, the metformin
      group was less likely to tolerate cisplatin, experienced more weight loss, had a
      tendency to receive lower doses of radiotherapy, required more feeding tube
      support, and had grade >=3 nausea/vomiting and hematological toxicities.
      CONCLUSION: Patients with head and neck cancer undergoing concurrent CRT along
      with metformin treatment require more careful multidisciplinary assessment and
      supportive care to ensure successful completion of treatment and avoid treatment
      related toxicities.

PMID- 28449194
TI  - Center of pressure profiles in unilateral compared to bilateral end-stage ankle
      osteoarthritis patients.
AB  - Ankle osteoarthritis (OA) compromises ankle joint stability in regards to static
      balance. Unilateral and bilateral osteoarthritis patients often exhibit different
      limb-loading patterns during static balance tasks. Symmetrical loading has been
      posited to improve balance performance. Therefore, the purpose of this study was
      to quantify balance performance in both ankle osteoarthritis patient groups.
      Twenty-two unilateral and twenty-one bilateral ankle osteoarthritis patients
      performed three 10-s quiet standing trials with their feet together. Ground
      reaction force data were collected from force platforms with one under each foot.
      Center of pressure excursion in the anteroposterior and mediolateral directions
      as well as the resultant center of pressure were calculated using custom Matlab
      software. A 2 * 2 repeated measures ANOVA with Cohen's d were used to analyze the
      differences between groups (unilateral vs. bilateral) and between limbs (affected
      vs. unaffected) (alpha = 0.05). No significant differences were found between
      limbs or groups in either the anteroposterior or mediolateral direction for any
      measured variable. Though not statistically different, moderate to large effect
      sizes were observed for mean resultant distance between unilateral and bilateral
      (d = 0.096, d: 1.0) as well as anteroposterior excursion (p = 0.077, d: 1.731)
      and mean velocity (p = 0.084, d: 1.50) between affected and unaffected limbs.
      These large effect sizes suggested clinically relevant differences may exist,
      particularly in the anteroposterior direction. These findings may suggest that
      center of pressure is a better measure of postural strategy while center of mass
      measures may be more representative of postural steadiness. (c) 2017 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2749-2754,
      2017.

PMID- 28449195
TI  - Reliable estimation of inhibitory efficiency: to anticipate, choose or simply
      react?
AB  - Response inhibition is an important executive process studied by clinical and
      experimental psychologists, neurophysiologists and cognitive neuroscientists
      alike. Stop-signal paradigms are popular because they are grounded in a theory
      that provides methods to estimate the latency of an unobservable process: the
      stop-signal reaction time (SSRT). Critically, SSRT estimates can be biased by
      skew of the response time distribution and gradual slowing over the course of the
      experiment. Here, we present a series of experiments that directly compare three
      common stop-signal paradigms that differ in the distribution of response times.
      The results show that the widely used choice response (CR) and simple response
      (SR) time versions of the stop-signal paradigm are particularly susceptible to
      skew of the response time distribution and response slowing, and that using the
      anticipated response (AR) paradigm based on the Slater-Hammel task offers a
      viable alternative to obtain more reliable SSRT estimates.

PMID- 28449196
TI  - Double trouble: Complement-mediated thrombotic microangiopathy in patients with
      hemoglobinopathies after stem cell transplantation.

PMID- 28449197
TI  - Safety profile of medication used during pregnancy: results of a multinational
      European study.
AB  - PURPOSE: The present study describes the safety profile of medications used
      during pregnancy across European countries and examines maternal factors
      associated with the use of risky medications during pregnancy. METHODS: This
      study is based on a multinational, web-based study conducted in 15 European
      countries from October 2011 to February 2012. Information about maternal
      demographics, illnesses, and medication use during pregnancy was collected via an
      electronic questionnaire. Pregnant women and new mothers with a child less than 1
      year-old could participate. The Swedish, Australian, and U.S. risk classification
      systems were used to evaluate medication safety. Descriptive statistics and
      generalized estimating equation models were used. RESULTS: A total of 587
      medications were reported by the study sample (n = 6657). Sixty-nine percent of
      the women used medications classified as safe, 28% used medications classified as
      risky, and 3% used medications with no classification available. Both socio
      demographic and medical factors were associated with the use of risky medications
      during pregnancy. Having a chronic disorder was the factor with the strongest
      association with the use of risky medications during pregnancy (adjusted odds
      ratio = 3.99, 95% confidence interval 3.54-4.49). CONCLUSIONS: The majority of
      women used medications classified as safe to use during pregnancy. However, a
      considerable proportion of women still used medications classified as risky.
      Having a chronic disorder was an important driver for using risky medications.
      Such use may still be appropriate when considering the woman's underlying
      condition. Pre-pregnancy counselling is important to ensure safe medication use
      for both mother and child. (c) 2017 The Authors. Pharmacoepidemiology & Drug
      Safety Published by John Wiley & Sons Ltd.

PMID- 28449198
TI  - Systematic review of sex work interventions in sub-Saharan Africa: examining
      combination prevention approaches.
AB  - OBJECTIVE: The incidence of HIV and sexually transmitted infections is
      disproportionately high among sex workers (SW). We aimed to update the evidence
      on the effectiveness of SW interventions in sub-Saharan Africa and to provide
      more insights into combination prevention. METHODS: The Systematic review
      followed PRISMA guidelines in a search of PUBMED and POPLINE for peer-reviewed
      literature published between 1 January 2000 and 22 July 2016 (registration number
      on PROSPERO: CRD42016042529). We considered cohort interventions, randomised
      controlled trials and cross-sectional surveys of SW programmes. A framework was
      used in the description and mapping of intervention to desired outcomes. RESULTS:
      Twenty-six papers(reporting on 25 studies) were included. A strategy that
      empowered peer educator leaders to steer community activities showed a twofold
      increase in coverage of behaviour change communication and utilisation of health
      facility among SW. Brief alcohol harm reduction effort demonstrated a significant
      effect on sexual violence and engagement in sex trading. A risk reduction
      counselling intervention among drug-injecting SW showed an effect on alcohol,
      substance use and engagement in sex work. No study on a promising intervention
      like PrEP among SWs was found. We observed that interventions that combined some
      structural components, biomedical and behavioural strategies tend to accumulate
      more desired outcomes. CONCLUSION: The evidence base that can be considered in
      intervention designs to prevent HIV in SW in SSA is vast. The health sector
      should consider interventions to reduce binge alcohol intake and intravenous drug
      use among sex workers. Programmes should staunchly consider multicomponent
      approaches that explore community-based structural approaches.

PMID- 28449200
TI  - Species' traits as predictors of range shifts under contemporary climate change:
      A review and meta-analysis.
AB  - A growing body of literature seeks to explain variation in range shifts using
      species' ecological and life-history traits, with expectations that shifts should
      be greater in species with greater dispersal ability, reproductive potential, and
      ecological generalization. Despite strong theoretical support for species' traits
      as predictors of range shifts, empirical evidence from contemporary range shift
      studies remains limited in extent and consensus. We conducted the first
      comprehensive review of species' traits as predictors of range shifts, collecting
      results from 51 studies across multiple taxa encompassing over 11,000 species'
      responses for 54 assemblages of taxonomically related species occurring together
      in space. We used studies of assemblages that directly compared geographic
      distributions sampled in the 20th century prior to climate change with resurveys
      of distributions after contemporary climate change and then tested whether
      species traits accounted for heterogeneity in range shifts. We performed a formal
      meta-analysis on study-level effects of body size, fecundity, diet breadth,
      habitat breadth, and historic range limit as predictors of range shifts for a
      subset of 21 studies of 26 assemblages with sufficient data. Range shifts were
      consistent with predictions based on habitat breadth and historic range limit.
      However, body size, fecundity, and diet breadth showed no significant effect on
      range shifts across studies, and multiple studies reported significant
      relationships that contradicted predictions. Current understanding of species'
      traits as predictors of range shifts is limited, and standardized study is needed
      for traits to be valid indicators of vulnerability in assessments of climate
      change impacts.

PMID- 28449199
TI  - Age at onset and the outcomes of schizophrenia: A systematic review and meta
      analysis.
AB  - The aim of this study was to analyse the effect of age at onset on the long-term
      clinical, social and global outcomes of schizophrenia through a systematic review
      and a meta-analysis. Original studies were searched from Web of Science,
      PsycINFO, Pubmed and Scopus, as well as manually. Naturalistic studies with at
      least a 2-year follow-up were included. Of the 3509 search results, 81 articles
      fulfilled the inclusion criteria. The meta-analysis was performed in Stata as a
      random-effect analysis with correlation coefficients between age at onset and the
      outcomes (categorized into remission, relapse, hospitalization, positive
      symptoms, negative symptoms, total symptoms, general clinical outcome,
      employment, social/occupational functioning and global outcome). There was a
      statistically significant (P < .05) correlation between younger age at onset and
      more hospitalizations (number of studies, n = 9; correlation, r = 0.17; 95%
      confidence interval, CI 0.09-0.25), more negative symptoms (n = 7; r = 0.14; 95%
      CI 0.01-0.27), more relapses (n = 3; r = 0.11; 95% CI 0.02-0.20), poorer
      social/occupational functioning (n = 12; r = 0.15; 95% CI 0.05-0.25) and poorer
      global outcome (n = 13; r = 0.14; 95% CI 0.07-0.22). Other relationships were not
      significant. This was the first systematic review of the effects of age at onset
      on the long-term outcomes of schizophrenia. The results show that age at onset
      has a small, but significant impact on some of the outcomes of schizophrenia.

PMID- 28449201
TI  - Silencing of Agrobacterium tumefaciens oncogenes ipt and iaaM induces resistance
      to crown gall disease in plum but not in apricot.
AB  - BACKGROUND: In this study, two vectors with short-length chimeric transgenes were
      used to produce Prunus rootstocks resistant to crown gall disease through RNA
      interference-mediated gene silencing of the Agrobacterium tumefaciens oncogenes
      ipt and iaaM. RESULTS: Transgenic plum and apricot lines were produced with
      efficiencies of up to 7.7 and 1.1% respectively. An in vitro evaluation method
      allowed identification of susceptible lines and reduction in the number of lines
      to be evaluated in the greenhouse. Five transgenic plum lines, expressing
      transgene-derived small interfering RNA (siRNA) and low levels of transgene
      hairpin RNA (hpRNA), showed a significant reduction in the development of the
      disease after infection with Agrobacterium strains C58 and A281 under greenhouse
      conditions. However, unexpectedly, all transgenic apricot lines were gall
      susceptible. The infection of apricot plants with a binary vector containing only
      the 6b oncogene demonstrated that the expression of this gene is involved in the
      induction of tumours in the apricot species. CONCLUSION: RNAi-mediated gene
      silencing can be used for inducing crown gall resistance in plum rootstocks.
      These could be used to graft non-genetically modified commercial fruit cultivars
      reducing, or eliminating, the disease symptoms. (c) 2017 Society of Chemical
      Industry.

PMID- 28449202
TI  - Barn owls maximize head rotations by a combination of yawing and rolling in
      functionally diverse regions of the neck.
AB  - Owls are known for their outstanding neck mobility: these birds can rotate their
      heads more than 270 degrees . The anatomical basis of this extraordinary neck
      rotation ability is not well understood. We used X-ray fluoroscopy of living owls
      as well as forced neck rotations in dead specimens and computer tomographic (CT)
      reconstructions to study how the individual cervical joints contribute to head
      rotation in barn owls (Tyto furcata pratincola). The X-ray data showed the
      natural posture of the neck, and the reconstructions of the CT-scans provided the
      shapes of the individual vertebrae. Joint mobility was analyzed in a spherical
      coordinate system. The rotational capability was described as rotation about the
      yaw and roll axes. The analyses suggest a functional division of the cervical
      spine into several regions. Most importantly, an upper region shows high rolling
      and yawing capabilities. The mobility of the lower, more horizontally oriented
      joints of the cervical spine is restricted mainly to the roll axis. These rolling
      movements lead to lateral bending, effectively resulting in a side shift of the
      head compared with the trunk during large rotations. The joints in the middle of
      the cervical spine proved to contribute less to head rotation. The analysis of
      joint mobility demonstrated how owls might maximize horizontal head rotation by a
      specific and variable combination of yawing and rolling in functionally diverse
      regions of the neck.

PMID- 28449204
TI  - Monocytes and macrophages in flow cytometry.

PMID- 28449203
TI  - Two cases of adenocarcinoma in situ arising in lobular endocervical glandular
      hyperplasia indicating localization of mucin on the cluster surface as an early
      cytological finding of malignant transformation.
AB  - Lobular endocervical glandular hyperplasia (LEGH) is an endocervical glandular
      hyperplastic lesion containing pyloric gland-like mucin, and has recently been
      recognized as a precursor lesion of malignant glandular lesions of the
      endocervix. The pyloric gland-like mucin contained in LEGH and gastric-type
      adenocarcinoma is observed as golden-yellowish by Papanicolaou staining. However,
      to our knowledge, the chronological course of the endocervical cytology of LEGH,
      eventually resulting in malignancy, has never been demonstrated to date. Here, we
      report two cases of gastric-type adenocarcinoma in situ (AIS) arising in LEGH,
      together with an analysis of their cytological course. In both cases,
      localization of mucin on the surface of glandular cell clusters was observed
      prior to nuclear atypia in endocervical cytology. In addition, the diagnosis of
      gastric-type AIS arising in LEGH was confirmed by pathological diagnosis of
      hysterectomy specimens in both cases. Histologically, all glandular cells of the
      LEGH without nuclear atypia contained a large amount of PAS-positive mucin. On
      the other hand, in atypical glandular cells, localization of the mucin on the
      luminal surface was observed, although mucin was abundant throughout the
      cytoplasm in some areas. Our cases show the course of acquirement of cytological
      atypia of LEGH, and indicate the significance of localization of mucin on the
      surface of glandular cell clusters as an early finding of the malignant
      transformation of LEGH in endocervical cytology. Our results indicate that the
      distribution of mucin in glandular cells should be analyzed together with nuclear
      atypia in the endocervical cytology of suspected cases of LEGH.

PMID- 28449206
TI  - President's Letter May 2017 Journal.

PMID- 28449205
TI  - Impact of pharmacist-involved collaborative care on the clinical, humanistic and
      cost outcomes of high-risk patients with type 2 diabetes (IMPACT): a randomized
      controlled trial.
AB  - WHAT IS KNOWN AND OBJECTIVE: With the increasing prevalence of diabetes, the
      physician-centred model is challenged to deliver holistic care in Asia. Diabetes
      may be managed effectively within a multidisciplinary collaborative care model;
      however, evidence on its effectiveness in Asian patients is lacking. Therefore,
      the primary objective was to evaluate the clinical outcomes of multidisciplinary
      collaborative care vs physician-centred care in diabetes. The secondary
      objectives were to evaluate humanistic and economic outcomes among the two types
      of care. METHODS: This 6-month prospective, open-label, parallel-arm, randomized,
      controlled study was conducted at four outpatient healthcare institutions. High
      risk patients aged >=21 years with uncontrolled type 2 diabetes, polypharmacy and
      comorbidities were included. Patients with type 1 diabetes or those who were
      unable to communicate independently were excluded. The control arm received usual
      care with referrals to nurses and dietitians as needed. The intervention arm
      (multidisciplinary collaborative care) was followed up with pharmacists
      regularly, in addition to receiving the usual care. The primary outcomes included
      HbA1c, systolic blood pressure, low-density lipoprotein and triglycerides. The
      secondary outcomes included scores from the Problem Areas in Diabetes (PAID) and
      the Diabetes Treatment Satisfaction Questionnaires (DTSQ), and diabetes-related
      health service utilization rates and costs. RESULTS AND DISCUSSION: Of 411
      eligible patients, 214 and 197 patients were randomized into the intervention and
      control arms, respectively. At 6 months, 141 patients in the intervention arm
      (65.9%) and 189 patients in the control arm (95.9%) completed the study. Mean
      HbA1c reduced from 8.6%+/-1.5% at baseline to 8.1%+/-1.3% at 6 months in the
      intervention arm (P=.04), with up to mean HbA1c improvement of 0.8% in patients
      with greater levels of uncontrolled glycemia. Whereas the mean HbA1c in the
      control arm remained unchanged (8.5%+/-1.4%) throughout the 6-month period.
      Improvements in PAID and DTSQ scores, reduction in physician workload and an
      average cost savings of US$91.01 per patient were observed in the intervention
      arm over 6 months. WHAT IS NEW AND CONCLUSIONS: The positive clinical, humanistic
      and economic outcomes highlighted the value of multidisciplinary collaborative
      care for Asian diabetic patients, thereby supporting the effectiveness of this
      approach in managing chronic diseases.

PMID- 28449207
TI  - Targeting anti-apoptotic BCL2 family proteins in haematological malignancies -
      from pathogenesis to treatment.
AB  - The B-cell lymphoma 2 (BCL2) family of proteins comprise key regulators of
      apoptosis and are implicated in the pathogenesis of many malignancies, including
      lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to
      tumour cells or render them more sensitive to chemotherapy. Inhibition of the
      anti-apoptotic functions of BCL2 proteins using structure-based design to produce
      specific inhibitors of protein-protein interactions has been achieved for BCL2,
      MCL1 and BCL-XL (also termed BCL2L1), providing an armamentarium of new targeted
      therapies called BH3-mimetics. The first BCL2-specific inhibitor, venetoclax, has
      shown extraordinary single agent activity in chronic lymphocytic leukaemia (CLL),
      with surprisingly little toxicity given the expression of BCL2 in normal tissues.
      Despite success in CLL, where sensitivity to BCL2 inhibition is seen in nearly
      all cases, key questions have not yet been addressed. For example, responses to
      venetoclax in other B-cell and myeloid malignancies are heterogeneous,
      highlighting the need to identify biomarkers that correlate with response and,
      secondly, to identify/develop other specific compounds that synergise with BCL2
      inhibition. In this review, we summarise the biology of BCL2 proteins, the
      mechanism of action of BH3-mimetics and the status of their clinical development
      in haematological malignancies.

PMID- 28449208
TI  - Complex modulation by stress of the effect of seizures on long term potentiation
      in mouse hippocampal slices.
AB  - Stress has a profound effect on ability to express neuronal plasticity, learning,
      and memory. Likewise, epileptic seizures lead to massive changes in brain
      connectivity, and in ability to undergo long term changes in reactivity to
      afferent stimulation. In this study, we analyzed possible long lasting
      interactions between a stressful experience and reactivity to pilocarpine, on the
      ability to produce long term potentiation (LTP) in a mouse hippocampus.
      Pilocarpine lowers paired pulse potentiation as well as LTP in CA1 region of the
      mouse hippocampal slice. When stress experience precedes exposure to pilocarpine,
      it protects the brain from the lasting effect of pilocarpine. When stress follows
      pilocarpine, it exacerbates the effect of the drug, to produce a long lasting
      reduction in LTP. These changes are accompanied by a parallel change in blood
      corticosterone level. A single exposure to selective mineralo- or gluco
      corticosterone (MR and GR, respectively) agonists and antagonists can mimic the
      stress effects, indicating that GR's underlie the lasting detrimental effects of
      stress whereas MRs are instrumental in counteracting the effects of stress. These
      studies open a new avenue of understanding of the interactive effects of stress
      and epileptic seizures on brain plasticity.

PMID- 28449209
TI  - The frequency of QTc prolongation among pediatric and young adult patients
      receiving methadone for cancer pain.
AB  - INTRODUCTION: A prolonged corrected QT (QTc) interval in pediatric patients is
      defined as >=470 msec. Methadone can cause a prolonged QTc interval that can lead
      to ventricular arrhythmias. The risk of methadone-induced prolongation of the QTc
      interval in children and young adults is unknown. The purpose of the study was to
      determine the frequency of QTc prolongation among pediatric and young adult
      patients with cancer pain on methadone treatment. METHODS: We retrospectively
      reviewed data for all patients on methadone during the study period. Qualifying
      patient data were reviewed to determine whether these patients had an
      electrocardiogram (ECG) while on methadone. The QTc values for analysis were
      manually calculated using the standard formula described by Bazett. RESULTS:
      Twenty-five patients were identified that met eligibility criteria. The median
      QTc decreased from baseline after initiation of methadone. QTc prolongation
      occurred in four of 25 (16%) patients and only one patient had a QTc greater than
      500 msec. This patient had 17 normal QTc intervals on methadone prior to the
      prolongation. After resolution of electrolyte abnormalities, six subsequent ECGs
      on methadone had a normal QTc interval. CONCLUSIONS: Prolongation of the QTc
      interval is infrequent. The only observed case was transient during multiple
      comorbid conditions. A prospective study is justified to better understand what
      role methadone plays as one of many risk factors for prolongation of the QTc
      interval in children and young adults.

PMID- 28449210
TI  - Middle meatal packing in endoscopic sinus surgery-to pack or not to pack?-a
      decision-analysis model.
AB  - BACKGROUND: Packing of the middle meatus and ethmoid cavities is a common
      practice in endoscopic sinus surgery (ESS), but its necessity recently has been
      challenged. The aim of this study was to formulate a decision-analysis model to
      determine the need for packing in ESS and identify variables affecting the
      decision. METHODS: A systematic review of the literature was conducted for all
      randomized control trials comparing packing to no packing in ESS, and a decision
      analysis model was generated. Probabilities and utilities were derived from the
      literature. Sensitivity analysis was used to determine which variables most
      affected the model. RESULTS: No packing was associated with better expected
      utilities than packing. On sensitivity analysis, packing was preferred when the
      disutility of no packing outweighed the disutility of packing, and when the
      probability for synechiae was greater than 35% without packing or lower than 2%
      with packing. When the component of packing removal was subtracted from the
      overall disutility simulating absorbable packing, the results favored packing.
      CONCLUSION: Our decision-analysis model indicates that middle meatal packing is
      not advantageous for patients undergoing ESS. Absorbable packing materials have a
      less adverse effect on quality of life than nonabsorbable materials. LEVEL OF
      EVIDENCE: 1a. Laryngoscope, 127:1506-1512, 2017.

PMID- 28449212
TI  - Predictors of success of external cephalic version and cephalic presentation at
      birth among 1253 women with non-cephalic presentation using logistic regression
      and classification tree analyses.
AB  - INTRODUCTION: Among women with a fetus with a non-cephalic presentation, external
      cephalic version (ECV) has been shown to reduce the rate of breech presentation
      at birth and cesarean birth. Compared with ECV at term, beginning ECV prior to 37
      weeks' gestation decreases the number of infants in a non-cephalic presentation
      at birth. The purpose of this secondary analysis was to investigate factors
      associated with a successful ECV procedure and to present this in a clinically
      useful format. MATERIAL AND METHODS: Data were collected as part of the Early ECV
      Pilot and Early ECV2 Trials, which randomized 1776 women with a fetus in breech
      presentation to either early ECV (34-36 weeks' gestation) or delayed ECV (at or
      after 37 weeks). The outcome of interest was successful ECV, defined as the fetus
      being in a cephalic presentation immediately following the procedure, as well as
      at the time of birth. The importance of several factors in predicting successful
      ECV was investigated using two statistical methods: logistic regression and
      classification and regression tree (CART) analyses. RESULTS: Among nulliparas,
      non-engagement of the presenting part and an easily palpable fetal head were
      independently associated with success. Among multiparas, non-engagement of the
      presenting part, gestation less than 37 weeks and an easily palpable fetal head
      were found to be independent predictors of success. These findings were
      consistent with results of the CART analyses. CONCLUSIONS: Regardless of parity,
      descent of the presenting part was the most discriminating factor in predicting
      successful ECV and cephalic presentation at birth.

PMID- 28449213
TI  - Femoral head fracture in a haemophilic arthropathy patient: a case report from
      China.

PMID- 28449211
TI  - Operational tolerance in kidney transplantation and associated biomarkers.
AB  - In the 1960s, our predecessors won a historical battle against acute rejection
      and ensured that transplantation became a common life-saving treatment. In
      parallel with this success, or perhaps because of it, we lost the battle for long
      lived transplants, being overwhelmed with chronic immune insults and the
      toxicities of immunosuppression. It is likely that current powerful treatments
      block acute rejection, but at the same time condemn the few circulating donor
      cells that would have been able to elicit immunoregulatory host responses towards
      the allograft. Under these conditions, spontaneously tolerant kidney recipients -
      i.e. patients who maintain allograft function in the absence of immunosuppression
      - are merely accidents; they are scarce, mysterious and precious. Several teams
      pursue the goal of finding a biomarker that would guide us towards the 'just
      right' level of immunosuppression that avoids rejection while leaving some space
      for donor immune cells. Some cellular assays are attractive because they are
      antigen-specific, and provide a comprehensive view of immune responses toward the
      graft. These seem to closely follow patient regulatory capacities. However, these
      tests are cumbersome, and require abundant cellular material from both donor and
      recipient. The latest newcomers, non-antigen-specific recipient blood
      transcriptomic biomarkers, offer the promise that a practicable and simple
      signature may be found that overcomes the complexity of a system in which an
      infinite number of individual cell combinations can lead possibly to graft
      acceptance. Biomarker studies are as much an objective - identifying tolerant
      patients, enabling tolerance trials - as a means to deciphering the underlying
      mechanisms of one of the most important current issues in transplantation.

PMID- 28449214
TI  - A rising incidence and poorer male outcomes characterise early onset paediatric
      inflammatory bowel disease.
AB  - BACKGROUND: The incidence of paediatric inflammatory bowel disease diagnosed
      before age 10 years is reportedly increasing, but national data are limited. AIM:
      To characterise the epidemiology, phenotype and clinical outcomes of children
      diagnosed with inflammatory bowel disease before age 10 years, and compare with
      data from children diagnosed aged 10-16 years. METHODS: A review of all Irish
      cases of early onset inflammatory bowel disease (diagnosis <10 years, EO-IBD)
      presenting between January 2000 and December 2014 was undertaken and compared to
      a cohort of later onset paediatric inflammatory bowel disease patients (diagnosis
      between 10 and 16 years, LO-IBD). Diagnostic investigations, phenotype,
      treatments, and long-term clinical and surgical outcomes were analysed. RESULTS:
      One hundred and ninety children (99 male) with EO-IBD were identified; 92 (48%)
      CD, 77 (41%) UC and 21 (11%) IBDU. The incidence of EO-IBD increased by 0.6 per
      100 000 per year (0.8-3.2 per 100 000 per year), with a significant increase in
      UC by 0.06 per 100 000 per year (P=.02). Males with CD had more upper GI disease
      (L4a; 48% vs 21%; P=.007), more extensive disease distribution (L3+/-L4; 31% vs
      11%; P=.05) and more severe disease activity at presentation (52% vs 31%; P=.05)
      than females. Fewer patients with early onset than later onset Crohn's disease
      had ileocolonic disease (L3; 10% vs 20%; P<.001). More relapses were observed in
      the first year post-diagnosis in early onset than later onset IBD (1.02 vs 0.5
      mean relapses; P<.001). CONCLUSIONS: EO-IBD is increasing in incidence. Males
      have more extensive and severe disease phenotypes, and younger patients have
      higher relapse rates than older children. Further research to explain these
      findings is warranted.

PMID- 28449215
TI  - Rapid degradation of longer DNA fragments enables the improved estimation of
      distribution and biomass using environmental DNA.
AB  - The advent of environmental DNA (eDNA) analysis methods has enabled rapid and
      wide-range ecological monitoring in aquatic ecosystems, but there is a dearth of
      information on eDNA degradation. The results of previous studies suggest that the
      decay rate of eDNA varies depending on the length of DNA fragments. To examine
      this hypothesis, we compared temporal change in copy number of long eDNA
      fragments (719 bp) with that of short eDNA fragments (127 bp). First, we isolated
      rearing water from a target fish species, Japanese Jack Mackerel (Trachurus
      japonicus), and then quantified the copy number of the long and short eDNA
      fragments in 1 L water samples after isolating the water from the fish. Long DNA
      fragments showed a higher decay rate than short fragments. Next, we measured the
      eDNA copy numbers of long and short DNA fragments using field samples, and
      compared them with fish biomass as measured by echo intensity. Although a
      previous study suggested that short eDNA fragments could be overestimated because
      of nontarget eDNA from a nearby fish market and carcasses, the eDNA
      concentrations of long fragments were correlated with echo intensity. This
      suggests that the concentration of longer eDNA fragments reflects fish biomass
      more accurately than the previous study by removing the effects of the fish
      market and carcasses. The length-related differences in eDNA have a substantial
      potential to improve estimation of species biomass.

PMID- 28449216
TI  - Molecular detection of Francisella noatunensis subsp. orientalis in cultured Nile
      tilapia (Oreochromis niloticus L.) in three Brazilian states.

PMID- 28449217
TI  - Job satisfaction and intention to stay within community and residential aged care
      employees.
AB  - OBJECTIVE: This study investigated the different facets of job satisfaction that
      influence community care and residential care employees' intention to stay in the
      aged care workforce. METHODS: A survey of four organisations in Australia was
      undertaken. t-Tests were conducted to analyse differences between groups.
      Regression analyses were performed to examine the factors influencing intentions
      to stay in the workforce. RESULTS: Community care workers were more satisfied
      with various facets of job satisfaction including work on their present job,
      supervision, people in their present job and the job in general. There was a
      difference between how the various facets of job satisfaction influenced
      intentions to stay for residential care compared to community care workers.
      CONCLUSIONS: Both workers were satisfied with their work conditions and work to
      different extents. There is an opportunity for residential care to look to the
      practices within the community care sector to improve employees' intentions to
      stay.

PMID- 28449218
TI  - Development and pharmacologic characterization of the rat 6 Hz model of partial
      seizures.
AB  - OBJECTIVE: The mouse 6 Hz model of psychomotor seizures is a well-established and
      commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its
      widespread use both in the identification and differentiation of novel ASDs in
      mice, a corresponding assay in rats has not been developed. We established a
      method for 6 Hz seizure induction in rats, with seizure behaviors similar to
      those observed in mice including head nod, jaw clonus, and forelimb clonus.
      METHODS: A convulsive current that elicits these seizure behaviors in 97% of rats
      (CC97 ) was determined using a Probit analysis. Numerous prototype ASDs were
      evaluated in this model using stimulus intensities of 1.5* and 2* the CC97 ,
      which is comparable to the approach used in the mouse 6 Hz seizure model (e.g.,
      32 and 44 mA stimulus intensities). The ASDs evaluated include carbamazepine,
      clobazam, clonazepam, eslicarbazepine, ethosuximide, ezogabine, gabapentin,
      lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, rufinamide,
      tiagabine, topiramate, and sodium valproate. Median effective dose (ED50 ) and
      median toxic (motor impairment) dose (TD50 ) values were obtained for each
      compound. RESULTS: Compounds that were effective at the 1.5 * CC97 stimulus
      intensity at protective index (PI) values >1 included clobazam, ethosuximide,
      ezogabine, levetiracetam, phenobarbital, and sodium valproate. Compounds that
      were effective at the 2 * CC97 stimulus intensity at PI values >1 included
      ezogabine, phenobarbital, and sodium valproate. SIGNIFICANCE: In a manner similar
      to the use of the mouse 6 Hz model, development of a rat 6 Hz test will aid in
      the differentiation of ASDs, as well as in study design and dose selection for
      chronic rat models of pharmacoresistant epilepsy. The limited number of
      established ASDs with demonstrable efficacy at the higher stimulus intensity
      suggests that, like the mouse 6 Hz 44 mA model, the rat 6 Hz seizure model may be
      a useful screening tool for pharmacoresistant seizures.

PMID- 28449219
TI  - The risk of gastric cancer in patients with gastric intestinal metaplasia in 5
      year follow-up.
AB  - BACKGROUND: Gastric intestinal metaplasia (GIM) is the premalignant stage of
      gastric cancer; however, consensus on its management has not been established.
      AIM: To determine the risk factors for gastric cancer in a population of patients
      with GIM to guide the appropriate clinical recommendations in a low prevalence
      area for gastric cancer. METHODS: This was a retrospective cohort study. Ninety
      one patients with GIM diagnosed between 2004 and 2014 were recruited for
      surveillance EGD every 6-12 months until a diagnosis of gastric cancer or
      completion of the planned 5-year follow-up duration. Possible risk factors for
      gastric cancer were assessed. RESULTS: At initial presentation, 81 of the 91
      patients (89%) had complete GIM, whereas the remaining 11% had a study entry
      diagnosis of incomplete GIM. No cancer developed amongst patients with complete
      GIM. In contrast, five of the 10 patients exhibiting incomplete GIM (50%)
      progressed to high-grade dysplasia (n=2) or cancer (n=3). Male gender (P=.027),
      and incomplete GIM (P=.001) were associated with high-risk histology (dysplasia
      or cancer) by study end. A trend suggested a possible association with smoking
      (P=.08). CONCLUSION: Male patients and those with incomplete GIM are at greatest
      risk of developing dysplasia or early gastric cancer. Further studies in
      determining optimal surveillance intervals and impact on cancer incidence and
      mortality are still required.

PMID- 28449220
TI  - Survival, Functional Status, and Eating Ability After Percutaneous Endoscopic
      Gastrostomy Tube Placement for Acute Stroke.
AB  - OBJECTIVES: To determine the long-term survival and independence of individuals
      with stroke and percutaneous endoscopic gastrostomy (PEG) tube placement. DESIGN:
      Retrospective cohort study. SETTING: A longitudinal nationally representative
      community-based sample of older adults. PARTICIPANTS: Individuals with stroke who
      had a PEG tube placed (N = 174, mean age 79, 51% female, 29% African American).
      MEASUREMENTS: Functional status before incident stroke was determined based on
      data from the Health and Retirement Study (HRS), a national longitudinal survey
      of community-dwelling older adults, from 1993 to 2012. Hospitalizations for
      stroke and PEG placement were determined according to Medicare claims. HRS
      participants were interviewed, and outcomes of survivors interviewed in the 2
      years after hospitalization are described. Survival and functional and eating
      ability of the cohort were examined. Groups were compared according to age and
      prestroke functional disability in activities of daily living (ADLs) because it
      was hypothesized that ADL disability would predict worse outcomes. RESULTS: In
      the 2 years after hospitalization, overall mortality was 66%. Fifteen
      participants survived and regained independent ADL function (9%). Of those who
      survived to a follow-up interview, 33 (56%) could not eat independently, and 31
      (53%) required assistance to walk across the room. Age of 85 and older was
      associated with worse outcomes (10% vs 29% at 2 years, P < .001), but baseline
      ADL disability was not. CONCLUSION: In this community-based sample, individuals
      who had had a stroke and a PEG tube placed had high mortality, and survivors were
      unlikely to be functional or mobile or to recover eating ability after
      hospitalization. A palliative care discussion including goals of care should
      occur before PEG tube placement is considered.

PMID- 28449221
TI  - Assessment of sun-protective attitudes and behaviours of australian medical
      students.

PMID- 28449223
TI  - The impact of a sibling's life-limiting genetic condition on adult brothers and
      sisters.
AB  - It is estimated that rare diseases affect the lives of over three million people
      in the United Kingdom. Of these, a significant proportion are children and young
      people with genetic life-limiting or life-shortening conditions. This study used
      a qualitative approach with in-depth semi-structured interviews to explore the
      experiences of 10 adult siblings of a baby diagnosed with Trisomy 13 (Patau
      syndrome) or Trisomy 18 (Edward syndrome). Findings illustrate that parental
      grief from the time of their child's diagnosis onward is also experienced by
      siblings. Although young adults may have conflicting feelings as a bereaved
      sibling, there is evidence that the experience impacts on their world views and
      their attitudes about prospective and expectant parenthood. The study highlights
      the importance of providing siblings with short-term and long-term support from
      the time of their brother's or their sister's diagnosis onward and provides new
      understanding about benefit of professional and peer support in helping young
      adults develop resilience and coping strategies.

PMID- 28449222
TI  - Tspan33 is Expressed in Transitional and Memory B Cells, but is not Responsible
      for High ADAM10 Expression.
AB  - Tetraspanins are a family of transmembrane proteins that form membrane
      microdomains. They play important roles in migration, adhesion and other cellular
      processes. TspanC8, a subfamily of tetraspanins, was found to associate and
      promote ADAM10 trafficking and cell surface localization. One of its members,
      Tspan33, is expressed in activated B cells. Using RT-PCR and flow cytometry, we
      analysed the pattern of expression of Tspan33 in B cells from healthy donors. We
      found Tspan33 expression in early and late stages of B cell development. However,
      Tspan33 expression did not correlate with ADAM10 surface expression. We also
      found expression of Tspan33 early in the activation process. Given its
      predominant expression in activated B cells and in several lymphomas, but not in
      naive B cells, we hypothesize that Tspan33 could be a potential target for
      therapeutic purposes.

PMID- 28449224
TI  - Validation of Ozone Monitoring Instrument UV Satellite Data Using Spectral and
      Broadband Surface Based Measurements at a Queensland Site.
AB  - This research reconstructed and validated the broadband UVA irradiances derived
      from discrete spectral irradiance data retrieved from the Ozone Monitoring
      Instrument (OMI) satellite from 1 January to 31 December 2009. OMI data at solar
      noon were compared to ground-based spectral irradiances at Toowoomba (27 degrees
      36' S 151 degrees 55' E), Australia, at 310, 324 and 380 nm for both cloud-free
      and all sky conditions. There was a strong relationship between the ground-based
      UV spectroradiometer data and satellite-based measurements with an R2 of 0.89 or
      better in each waveband for cloud-free days. The data show an overestimate of the
      satellite-derived spectral irradiances compared to the ground-based data. The
      models developed for the subtropical site data account for this overestimation
      and are essential for any data correlation between satellite- and ground-based
      measurements. Additionally, this research has compared solar noon broadband UVA
      irradiances evaluated with a model and the discrete satellite spectral
      irradiances for the solar noon values of cloud-free days to those measured with a
      ground-based UVA radiometer. An R2 of 0.86 was obtained confirming that for cloud
      free days the broadband UVA can be evaluated from the OMI satellite spectral
      irradiances.

PMID- 28449225
TI  - Transfusion research priorities for blood services in sub-Saharan Africa.
AB  - Evidence to support many blood transfusion policies and practices in sub-Saharan
      Africa (SSA) is weak or lacking. SSA cannot extrapolate from wealthy countries'
      research findings because its environment, users and structures are very
      different and SSA has critical blood shortages. SSA needs to generate its own
      evidence but research funds are very scarce and need to be carefully targeted to
      match need. This study aimed to define this need by determining research
      priorities for blood services in SSA. Thirty-five stakeholders representing
      diverse blood services' interests and expertise participated in a workshop. An
      adapted 'consensus development method' was used to identify, agree and justify
      research priorities under five themes through small group and plenary discussion,
      and cumulative voting. Research priorities covered traditional research areas,
      such as clinical use of blood and infection screening, but also highlighted many
      new, under-researched topics, mostly concerning blood service 'systems', such as
      economics, blood components and regulation. Lack of electronic information
      management systems was an important hindrance to the blood services' ability to
      generate robust research data. This study has identified and prioritised novel
      research that will help blood services in SSA to address their own needs
      including their most urgent problem: the lack of access to adequate blood
      supplies. To catalyse this research blood services in SSA need to enhance their
      capacity to conduct, commission and manage research and to strengthen their
      collaborations within and beyond Africa.

PMID- 28449226
TI  - An integrated network analysis identifies how ArcAB enables metabolic
      oscillations in the nitric oxide detoxification network of Escherichia coli.
AB  - The virulences of many pathogens depend on their abilities to detoxify the immune
      antimicrobial nitric oxide (NO*). The functions of bacterial NO* detoxification
      machinery depend on oxygen (O2 ), with O2 inhibiting some enzymes, whereas others
      use it as a substrate. Previously, Escherichia coli NO* detoxification was found
      to be highly attenuated under microaerobic conditions and metabolic oscillations
      were observed. The oscillations in [NO*] and [O2 ] were found to result from the
      inhibitory action of NO* on aerobic respiration, the catalytic inactivation of
      NO* by Hmp (an NO* dioxygenase), and an imbalanced competition for O2 between Hmp
      and cytochrome terminal oxidase activity. Here the authors investigated the role
      of the ArcAB two component system (TCS) in microaerobic NO* detoxification. The
      authors observed that wild-type, DeltaarcA, and DeltaarcB had comparable initial
      NO* clearance times; however, the mutant cultures failed to exhibit [NO*] and [O2
      ] oscillations. Using an approach that employed experimentation and computational
      modeling, the authors found that the loss of oscillations in DeltaarcA was due to
      insufficient induction of cytochrome bd-I expression. Collectively, these results
      establish ArcAB as a TCS that influences NO* detoxification in E. coli within the
      physiologically-relevant microaerobic regime.

PMID- 28449227
TI  - Apremilast for a psoriasis patient with HIV and hepatitis C.

PMID- 28449228
TI  - Azathioprine dose reduction in inflammatory bowel disease patients on combination
      therapy: an open-label, prospective and randomised clinical trial.
AB  - BACKGROUND: Infliximab (IFX) combined with azathioprine (AZA) is more effective
      than IFX monotherapy in inflammatory bowel disease (IBD). AIM: To identify the
      AZA optimal dose that is required for efficacy when receiving combination
      therapy. METHODS: Patients with IBD in durable remission on combination therapy
      were enrolled in a 1-year, open-label, prospective trial after randomisation into
      three groups: AZA steady (2-2.5 mg/kg/day, n=28) vs AZA down (dose was halved 1
      1.25 mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined
      as occurrence of a clinical relapse and/or any change in IBD therapy. RESULTS:
      Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%)
      patients experienced failure at 1 year in groups AZA steady, AZA down and AZA
      stopped, respectively (P=.1 across the groups). The median trough levels of IFX
      at inclusion were close to those measured at the end of follow-up in group AZA
      steady (3.65 vs 3.45 MUg/mL, P=.9) and in group AZA down (3.95 vs 3.60 MUg/mL,
      P=.5), whereas these levels dropped from 4.25 to 2.15 MUg/mL (P=.02) in group AZA
      stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an
      unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and
      AZA stopped, respectively. A threshold of 6-TGN <105 pmoles/8.108 RBC was
      associated with an unfavourable evolution of IFX pharmacokinetics. CONCLUSIONS:
      Under combination therapy, AZA dose reduction, but not withdrawal, appears to be
      as effective as continuation of AZA at full dose.

PMID- 28449229
TI  - Exposure to texture of foods for 8-month-old infants: Does the size of the pieces
      matter?
AB  - This study examined the effect of meals varying in amount, size, and hardness of
      food pieces on the development of the chewing capabilities of 8-month-old
      infants. The study also examined changes in shivering, gagging, coughing,
      choking, and their ability to eat from a spoon. In an in-home setting two groups
      were given commercially available infant meals and fruits, purees with either
      less, smaller and softer or more, larger and harder pieces. Both groups were
      given these foods for 4 weeks and were monitored several times during this
      period. After the 4-week exposure period infants in both groups were given the
      same five test foods. Structured questionnaires with questions on eating behavior
      and the child's development were conducted 6 times in the 4 to 12-month period
      and video analyses of feedings were conducted 4 times between 8 and 9 months.
      After the 4-week exposure period, the group that had been exposed to the foods
      with more, larger and harder pieces showed a significantly higher rating for
      chewing a piece of carrot and potato for the first time, but not for a piece of
      banana nor for mashed foods. Shivering, gagging, coughing, choking, and ability
      to eat from a spoon were not different between the two groups. These results
      contribute to the insight that exposure to texture is important for young
      children to learn how to handle texture. PRACTICAL APPLICATIONS: (a) The study
      shows the feasibility of testing the effects of texture interventions on chewing
      capability and oral responses such as gagging, coughing, and choking in infants.
      (b) The study contributes to the insight that exposure to food texture to learn
      how to handle texture is important for infants and showed that exposing children
      to a higher amount of larger pieces improves their chewing capability for a piece
      of carrot and potato, at least immediately after the intervention.

PMID- 28449230
TI  - Metal-Free Arene and Heteroarene Borylation Catalyzed by Strongly Electrophilic
      Bis-boranes.
AB  - The geminal chelate bis-borylalkanes 4 and 5 featuring strongly electrophilic
      B(C6 F5 )2 and B(C6 F5 ) groups, respectively, serve as efficient catalysts for
      the borylation of arenes and heteroarenes. The borylation reactions proceed under
      mild conditions with liberation of dihydrogen.

PMID- 28449231
TI  - Resource partitioning in tolerant and intolerant macaques.
AB  - The clumped distribution of food resources promotes food defensibility and can
      lead to the monopolizing of resources by high-ranking individuals. However, the
      balance of power is set at different levels according to societies, meaning that
      resource partitioning should vary between them. This study investigates whether
      dominance asymmetry and resource partitioning are related in non-human primates
      by comparing two species with contrasting social styles, namely rhesus macaques
      (Macaca mulatta) which display strong social intolerance and a steep gradient of
      dominance, and Tonkean macaques (Macaca tonkeana), which exhibit higher levels of
      tolerance and more balanced dominance relationships. Study groups were kept in
      semi-free ranging conditions. Animals were provided with fruit in three different
      clumped conditions during 30-min trials. We found that higher-ranking rhesus
      macaques had priority for the access to fruit: these individuals spent longer in
      the feeding area in the first 10-min period of trials, while lower-ranking
      individuals had diminished access to fruit under the most clumped condition; this
      was associated with sustained agonistic interactions. Dominance effects were
      weaker in Tonkean macaques. They exhibited co-feeding between high- and low
      ranking individuals in the first period; there was no significant effect of
      dominance even in the most clumped condition; and frequencies of agonistic
      interactions remained moderate relative to the number of individuals present in
      the feeding area. These results show that food resources were more equitably
      distributed among group members in tolerant macaques than in their intolerant
      counterparts. Dominance gradient and social tolerance may be considered as two
      aspects of the same phenomenon.

PMID- 28449232
TI  - Safety, pharmacokinetics and pharmacological effects of the selective androgen
      receptor modulator, GSK2881078, in healthy men and postmenopausal women.
AB  - AIM: Selective androgen receptor modulators (SARMs) induce anabolic effects on
      muscle without the adverse effects of androgenic steroids. In this first-in-human
      study, we report the safety, tolerability, pharmacokinetics (PK) and
      pharmacodynamics of the SARM GSK2881078. METHODS: In Part A, healthy young men (n
      = 10) received a single dose of study drug (0 mg, 0.05 mg, 0.1 mg, 0.2 mg
      GSK2881078 or matching-placebo). In Part B, repeat-dose cohorts in men (n = 65)
      were 0.05 mg, 0.2 mg then 0.08 mg, 0.24 mg, 0.48 mg, 0.75 mg, or placebo; in
      women (n = 24) they were 0.24 mg, 0.35 mg, or placebo (7 days for 0.5 mg, 14 days
      for other doses). RESULTS: PK analysis showed dose-proportional increases in
      exposure and a long >100-h half-life. No significant effects on vital signs,
      electrocardiograms, cardiac telemetry or standard clinical laboratory studies
      were observed. A dose-response effect was observed on lowering both high-density
      lipoprotein and sex hormone-binding globulin. In females at 0.35 mg, differences
      from placebo were -0.518 (95% confidence interval: -0.703, -0.334) mmol l-1 and 
      39.1 (-48.5, -29.7) nmol l-1 , respectively. Women showed greater sensitivity to
      these parameters at lower doses than men. Drug-related adverse events (AEs) were
      mild. One woman developed a drug rash and was withdrawn. Two men had elevated
      creatine phosphokinase after physical exertion during follow-up. A serious AE
      occurred in a subject on placebo. CONCLUSIONS: These data demonstrate
      pharmacodynamic effects with acceptable tolerability and support further clinical
      evaluation of this SARM.

PMID- 28449233
TI  - An evaluation of the International Society for Animal Genetics recommended
      parentage and identification panel for the domestic pigeon (Columba livia
      domestica).
AB  - In this study, the International Society for Animal Genetics (ISAG) recommended
      panel for the identification of the domestic pigeon (Columba livia domestica) is
      characterized based on commonly used statistical parameters. The marker panel is
      based on 16 short tandem repeat (STR) loci (PIGN15, PIGN10, PIGN57, PIGN26,
      CliMUD16, CliMUD19, PIGN12, CliMUD17, CliMUT17, PIGN04, CliMUD01, CliMUD11,
      CliMUD35, CliMUT02, CliMUT13, CliMUT43). The alleles of the 16 loci consist of a
      mixture of tri-, tetra-, penta- and hexameric repeat patterns. A sex
      determination marker was included in the multiplex for quality control. The
      repeat sequence of the PIGN markers was previously unpublished and therefore
      sequenced to reveal the sequence pattern. In total, 1421 pigeons were genotyped
      on 16 STR loci to generate allele frequency data for each locus. For all 16
      markers combined, a PE1 (combined non-exclusion probability, first parent) of
      0.9986 and PE2 (combined non-exclusion probability, second parent) of >0.9999 was
      observed. Comparing the alleged father and mother, a PE value of >0.9999 was
      observed. Two of the markers, CliMUD19 and PIGN12, were found to have relatively
      high Hardy-Weinberg equilibrium and F(null) values. Therefore these markers may
      be considered to be replaced by other STRs. Another point of discussion may be to
      add a gender identification marker to the recommended ISAG panel. Not only can
      this serve as an extra identification marker, but this can also confirm the sex
      of a sample, because it is challenging to determine the sex based on phenotypical
      characteristics, especially for chicks. In conclusion, the set of 16 STR markers
      can be used in routine parentage verification and the identification of
      individuals.

PMID- 28449234
TI  - Magnetic resonance imaging and computed tomographic characteristics of a glioma
      causing calvarial erosion in a dog.
AB  - An 8-year-old female Boxer was examined for acute onset of seizures. On magnetic
      resonance imaging (MRI), an intra-axial mass with imaging features consistent
      with glioma was observed in the right cerebral hemisphere. A defect in the
      temporal bone adjacent to the mass was observed. Postmortem computed tomography
      (CT) confirmed temporal bone osteolysis and necropsy demonstrated a glioblastoma
      with associated calvarial erosion. Although occasionally described in human
      medicine, to our knowledge, this is the first description of a brain glioma
      causing calvarial erosion in a dog. Glioma should be included as a differential
      diagnosis for intracranial lesions that could cause bony changes in the skull.

PMID- 28449236
TI  - Discovery of LHRH and development of LHRH analogs for prostate cancer treatment.
AB  - The discovery, isolation, elucidation of structure, synthesis, and initial
      testing of the neuropeptide hypothalamic luteinizing hormone-releasing hormone
      (LHRH), which regulates reproduction, is briefly described. The design,
      synthesis, and experimental and clinical testing of agonistic analogs of LHRH is
      extensively reviewed focusing on the development of new methods for the treatment
      of prostate cancer. Subsequent development of antagonistic analogs of LHRH is
      then faithfully recounted with special emphasis on therapy of prostate cancer and
      BPH. The concepts of targeted therapy to peptide receptors on tumors are re
      examined and the development of the cytotoxic analogs of LHRH and their status is
      reviewed. The endeavor to develop better therapies for prostate cancer, based on
      LHRH analogs, guided much of our work.

PMID- 28449237
TI  - The environmental and host-associated bacterial microbiota of Arctic seawater
      farmed Atlantic salmon with ulcerative disorders.
AB  - The Norwegian aquaculture of Atlantic salmon (Salmo salar L.) is hampered by
      ulcerative disorders associated with bacterial infections. Chronic ulceration may
      provide microenvironments that disturb the normal microbial biodiversity of
      external surfaces. Studying the composition of microbial communities in skin
      ulcers will enhance our understanding of ulcer aetiology. To achieve this, we
      tested marine farmed Atlantic salmon and sampled the base and edge of ulcers at
      the end of winter (April) and end of summer (September), in addition to skin
      mucus of healthy individuals. In order to assess microbiota associated with the
      host and obtain insight into the environmental ecology, we also sampled sea
      water, the sediment layer underneath the farm facility and the distal intestine
      of Atlantic salmon. The skin microbiota of Atlantic salmon was different from
      that of the surrounding water. Residential Tenacibaculum and Arcobacter species
      persistently dominated the cutaneous skin and ulcer mucus surfaces of Atlantic
      salmon during both winter and summer periods. The intestinal microbiota was
      dominated by Mycoplasma with an increase in Aliivibrio and Alcaligenes abundance
      in the intestine of fish with ulcerative disorder at the end of winter. These
      findings suggest the presence of resilient microbes in the mucus surfaces of
      Atlantic salmon.

PMID- 28449235
TI  - Psychometric properties of the Mental Health and Social Inadaptation Assessment
      for Adolescents (MIA) in a population-based sample.
AB  - We report on the psychometric properties of the Mental Health and Social
      Inadaptation Assessment for Adolescents (MIA), a self-report instrument for
      quantifying the frequency of mental health and psychosocial adaptation problems
      using a dimensional approach and based on the DSM-5. The instrument includes 113
      questions, takes 20-25 minutes to answer, and covers the past 12 months. A
      population-based cohort of adolescents (n = 1443, age = 15 years; 48% males)
      rated the frequency at which they experienced symptoms of Attention Deficit
      Hyperactivity Disorder (ADHD), Conduct Disorder, Oppositional Defiant Disorder,
      Depression, Generalized Anxiety, Social Phobia, Eating Disorders (i.e. DSM
      disorders), Self-harm, Delinquency, Psychopathy as well as social adaptation
      problems (e.g. aggression). They also rated interference with functioning in four
      contexts (family, friends, school, daily life). Reliability analyses indicated
      good to excellent internal consistency for most scales (alpha = 0.70-0.97) except
      Psychopathy (alpha = 0.46). The hypothesized structure of the instrument showed
      acceptable fit according to confirmatory factor analysis (CFA) [Chi-square (4155)
      = 9776.2, p = 0.000; Chi-square/DF = 2.35; root mean square error of
      approximation (RMSEA) = 0.031; Comparative Fit Index (CFI) = 0.864], and good
      convergent and discriminant validity according to multitrait-multimethods
      analysis. This initial study showed adequate internal validity and reliability of
      the MIA. Our findings open the way for further studies investigating other
      validity aspects, which are necessary before recommending the wide use of the MIA
      in research and clinical settings.

PMID- 28449238
TI  - Exposure-response relationship of neighbourhood sanitation and children's
      diarrhoea.
AB  - OBJECTIVES: To assess the association of neighbourhood sanitation coverage with
      under-five children's diarrhoeal morbidity and to evaluate its exposure-response
      relationship. METHODS: We used the Demographic and Health Surveys (DHS) of 29
      developing countries in sub-Saharan Africa and South Asia, conducted between 2010
      and 2014. The primary outcome was two-week incidence of diarrhoea in children
      under 5 years of age (N = 269014). We conducted three-level logistic regression
      analyses and applied cubic splines to assess the trend between neighbourhood
      level coverage of improved household sanitation and diarrhoeal morbidity.
      RESULTS: A significant association between neighbourhood-level coverage of
      improved household sanitation and diarrhoeal morbidity (OR [95% CI] = 0.68 [0.62
      0.76]) was found. Exposure-relationship analyses results showed improved
      sanitation coverage threshold at 0.6. We found marginal degree of association (OR
      [95% CI] = 0.82 [0.77-0.87]) below the threshold, which, beyond the threshold,
      sharply increased to OR of 0.44 (95% CI: 0.29-0.67) at sanitation coverage of 1
      (i.e. neighbourhood-wide use of improved household sanitation). Similar exposure
      response trends were identified for urban and rural subgroups. CONCLUSIONS: Our
      findings suggest that neighbourhood sanitation plays a key role in reducing
      diarrhoeal diseases and that increase in sanitation coverage may only have
      minimal impact on diarrhoeal illness, unless sufficiently high coverage is
      achieved.

PMID- 28449239
TI  - The Role of the Nuclear Envelope Protein MAN1 in Mesenchymal Stem Cell
      Differentiation.
AB  - Mutations in MAN1, a protein of the nuclear envelope, cause bone phenotypes
      characterized by hyperostosis. The mechanism of this pro-osteogenic phenotype
      remains unknown. We increased and decreased MAN1 expression in mesenchymal stem
      cells (MSC) upon which standard osteogenic and adipogenic differentiation were
      performed. MAN1 knockdown increased osteogenesis and mineralization. In contrast,
      osteogenesis remained stable upon MAN1 overexpression. Regarding a mechanism, we
      found that low levels of MAN1 facilitated the nuclear accumulation of regulatory
      smads and smads-related complexes, with a concurrently high expression of nuclear
      beta-Catenin. In addition, we found adipogenesis to be decreased in both
      conditions, although predominantly affected by MAN1 overexpression. Finally,
      lamin A, a protein of the nuclear envelope that regulates MSC differentiation,
      was unaffected by changes in MAN1. In conclusion, our studies demonstrated that
      lower levels of MAN1 in differentiating MSC are associated with higher
      osteogenesis and lower adipogenesis. High levels of MAN1 only affected
      adipogenesis. These effects could have an important role in the understanding of
      the role of the proteins of the nuclear envelope in bone formation. J. Cell.
      Biochem. 118: 4425-4435, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28449240
TI  - Bone morphogenetic protein signalling in pulmonary hypertension: advances and
      therapeutic implications.
AB  - NEW FINDINGS: What is the topic of this review? This review covers recent
      evidence highlighting the crucial pathophysiological roles and molecular
      mechanisms of the bone morphogenetic protein (BMP) signalling pathway during the
      progression of pulmonary hypertension (PH) and discusses targeting of BMP
      signalling as a new treatment option against PH. What advances does it highlight?
      A series of breakthrough findings have greatly enriched our understanding about
      the mechanism of action of BMP signalling in PH and proved the feasibility of BMP
      targeting strategies in experimental PH models. This review collects these ideas
      and discusses the frontiers of BMP signalling-targeted PH therapy at different
      steps of the signal transduction. The bone morphogenetic protein (BMP)-mediated
      signalling pathway plays crucial roles in the development and progression of
      pulmonary hypertension (PH). Typical BMP signalling involves BMP ligands,
      specific transmembrane serine/threonine kinase receptors, cellular responsive
      kinases and secreted antagonists. As more and more studies have been conducted,
      the specific protective or pathogenic roles of these molecules within all these
      subgroups of BMP signalling have been continuously uncovered. Based on this
      evidence, specific strategies have been designed by targeting these factors as a
      new treatment approach to PH. In this review, we have collected recent advances
      in the exciting findings that link BMP signalling with the pathogenesis of PH and
      we discuss the potential future frontiers in therapeutic design.

PMID- 28449241
TI  - Autophagy compensates impaired energy metabolism in CLPXP-deficient Podospora
      anserina strains and extends healthspan.
AB  - The degradation of nonfunctional mitochondrial proteins is of fundamental
      relevance for maintenance of cellular homeostasis. The heteromeric CLPXP protein
      complex in the mitochondrial matrix is part of this process. In the fungal aging
      model Podospora anserina, ablation of CLPXP leads to an increase in healthy
      lifespan. Here, we report that this counterintuitive increase depends on a
      functional autophagy machinery. In PaClpXP mutants, autophagy is involved in
      energy conservation and the compensation of impairments in respiration.
      Strikingly, despite the impact on mitochondrial function, it is not mitophagy but
      general autophagy that is constitutively induced and required for longevity. In
      contrast, in another long-lived mutant ablated for the mitochondrial PaIAP
      protease, autophagy is neither induced nor required for lifespan extension. Our
      data provide novel mechanistic insights into the capacity of different forms of
      autophagy to compensate impairments of specific components of the complex
      mitochondrial quality control network and about the biological role of
      mitochondrial CLPXP in the control of cellular energy metabolism.

PMID- 28449243
TI  - Pathologic features of mycobacteriosis in naturally infected Syngnathidae and
      novel transcriptome assembly in association with disease.
AB  - Syngnathidae (seahorses, seadragons and pipefish) suffer significant losses from
      non-tuberculous mycobacteria. However, they produce markedly different lesions in
      response to the disease compared to other teleost species, notably infrequent
      granuloma formation. This study evaluated 270 syngnathid fish, from which 92 were
      diagnosed with mycobacteriosis by histopathology, culture or both. Microscopic
      lesions variably consisted of random foci of coagulative necrosis in multiple
      organs, containing high numbers of free bacteria and large aggregates or sheets
      of macrophages with cytoplasm laden with acid-fast bacilli. Mycobacterial
      associated granulomas were identified in only six seahorses. Five fish had
      positive cultures with no observed microscopic changes. RNA-seq of the head
      kidney was performed to investigate the transcriptome of two infected and six non
      infected lined seahorses Hippocampus erectus. Assembled and annotated putative
      transcripts serve to enrich the database for this species, as well as provide
      baseline data for understanding the pathogenesis of mycobacteriosis in seahorses.
      Putative components of the innate immune system (IL-1beta, IL-6, TNF, NOS, Toll
      like receptor 1, MHC Class I, NF-kappabeta, transforming growth factor beta,
      MyD88) were identified in the RNA-seq data set. However, a homolog for a key
      component in the TH1 adaptive immune response, interferon-gamma, was not
      identified and may underlie the unique pathologic presentation.

PMID- 28449242
TI  - Resting sympathetic arousal moderates the association between parasympathetic
      reactivity and working memory performance in adults reporting high levels of life
      stress.
AB  - The neurovisceral integration model stipulates that autonomic function plays a
      critical role in the regulation of higher-order cognitive processes, yet most
      work to date has examined parasympathetic function in isolation from sympathetic
      function. Furthermore, the majority of work has been conducted on normative
      samples, which typically demonstrate parasympathetic withdrawal to increase
      arousal needed to complete cognitive tasks. Little is known about how autonomic
      regulation supports cognitive function in populations exposed to high levels of
      stress, which is critical given that chronic stress exposure alters autonomic
      function. To address this, we sought to characterize how parasympathetic (high
      frequency heart rate variability, HF-HRV) and sympathetic (preejection period,
      PEP) measures of cardiac function contribute to individual differences in working
      memory (WM) capacity in a sample of high-risk women. HF-HRV and PEP were measured
      at rest and during a visual change detection measure of WM. Multilevel modeling
      was used to examine within-person fluctuations in WM performance throughout the
      task concurrently with HF-HRV and PEP, as well as between-person differences as a
      function of resting HF-HRV and PEP levels. Results indicate that resting PEP
      moderated the association between HF-HRV reactivity and WM capacity. Increases in
      WM capacity across the task were associated with increases in parasympathetic
      activity, but only among individuals with longer resting PEP (lower sympathetic
      arousal). Follow-up analyses showed that shorter resting PEP was associated with
      greater cumulative risk exposure. These results support the autonomic space
      framework, in that the relationship between behavior and parasympathetic function
      appears dependent on resting sympathetic activation.

PMID- 28449244
TI  - Indications and extent of central neck dissection for papillary thyroid cancer:
      An American Head and Neck Society Consensus Statement.
AB  - BACKGROUND: The primary purposes of this interdisciplinary consensus statement
      were to review the relevant indications for central neck dissection (CND) in
      patients with papillary thyroid cancer (PTC) and to outline the appropriate
      extent and relevant techniques required to accomplish a safe and effective CND.
      METHODS: A writing group convened by the American Head and Neck Society (AHNS)
      Endocrine Committee was tasked with identifying the important clinical elements
      to consider when managing the central neck compartment in patients with PTC based
      on available evidence in the literature, and the group's collective experience.
      The position statement paper was then submitted to the full Endocrine Committee,
      Education Committee, and AHNS Council. RESULTS: This consensus statement was
      developed to inform the clinical decision-making process when managing the
      central neck compartment in patients with PTC from the AHNS. This document is
      intended to provide clarity through definitions as well as a basic guideline from
      which to manage the central neck. It is our hope that this improves the quality
      and reduces variation in management of the central neck, facilitates
      communication, and furthers research for patients with thyroid cancer.
      CONCLUSION: This represents, in our opinion, contemporary optimal surgical care
      for this patient population and is endorsed by the American Head and Neck
      Society. (c) 2017 Wiley Periodicals, Inc. Head Neck 39: 1269-1279, 2017.

PMID- 28449245
TI  - Characterization of a Poly-4-Vinylpyridine-Supported CuPd Bimetallic Catalyst for
      Sonogashira Coupling Reactions.
AB  - CuPd bimetallic solvated metal atoms (SMA) synthesized by metal vapor synthesis
      (MVS) technique and supported on poly-4-vinylpyridine (PVPy) resin, showed
      significantly higher catalytic activity in Sonogashira-type carbon-carbon
      coupling reactions than the corresponding monometallic Cu and Pd systems as well
      as their physical mixture. The analysis of the bimetallic catalyst combining
      transmission electron microscopy techniques and X-ray absorption fine structure
      (XAFS) spectroscopy revealed the presence of small Pd nanoparticles (dm =2.5 nm)
      while the analysis of the X-ray absorption data, at the Cu K-edge suggests the
      formation of thin and incomplete Cu oxide layers around the Pd-rich cores.

PMID- 28449246
TI  - Review article: hepatitis E-a concise review of virology, epidemiology, clinical
      presentation and therapy.
AB  - BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis
      and acute liver failure in the developing world. During the last decade, there
      has been increasing recognition of autochthonous (locally acquired) HEV infection
      in developed countries. Chronic HEV infection is now recognised, and in
      transplant recipients this may lead to cirrhosis and organ failure. AIM: To
      detail current understanding of the molecular biology of HEV, diagnostic and
      therapeutic strategies and propose future directions for basic science and
      clinical research. METHODS: PubMed was searched for English language articles
      using the key words "hepatitis E", "viral hepatitis", "autochthonous infection",
      "antiviral therapy", "liver transplantation", "acute", "chronic", "HEV",
      "genotype", "transmission" "food-borne", "transfusion". Additional relevant
      publications were identified from article reference lists. RESULTS: There has
      been increasing recognition of autochthonous HEV infection in Western countries,
      mainly associated with genotype 3. Chronic HEV infection has been recognised
      since 2008, and in transplant recipients this may lead to cirrhosis and organ
      failure. Modes of transmission include food-borne transmission, transfusion of
      blood products and solid organ transplantation. Ribavirin therapy is used to
      treat patients with chronic HEV infection, but new therapies are required as
      there have been reports of treatment failure with ribavirin. CONCLUSIONS:
      Autochthonous HEV infection is a clinical issue with increasing burden. Future
      work should focus on increasing awareness of HEV infection in the developed
      world, emphasising the need for clinicians to have a low threshold for HEV
      testing, particularly in immunosuppressed patients. Patients at potential risk of
      chronic HEV infection must also be educated and given advice regarding prevention
      of infection.

PMID- 28449247
TI  - Informant discrepancy defines discrete, clinically useful autism spectrum
      disorder subgroups.
AB  - BACKGROUND: Discrepancy between informants (parents and teachers) in severity
      ratings of core symptoms commonly arise when assessing autism spectrum disorder
      (ASD). Whether such discrepancy yields unique information about the ASD phenotype
      and its clinical correlates has not been examined. We examined whether degree of
      discrepancy between parent and teacher ASD symptom ratings defines discrete,
      clinically meaningful subgroups of youth with ASD using an efficient, cost
      effective procedure. METHODS: Children with ASD (N = 283; 82% boys; Mage  = 10.5
      years) were drawn from a specialty ASD clinic. Parents and teachers provided
      ratings of the three core DSM-IV-TR domains of ASD symptoms (communication,
      social, and perseverative behavior) with the Child and Adolescent Symptom
      Inventory-4R (CASI-4R). External validators included child psychotropic
      medication status, frequency of ASD-relevant school-based services, and the
      Autism Diagnostic Observation Schedule (ADOS-2). RESULTS: Four distinct subgroups
      emerged that ranged from large between-informant discrepancy (informant-specific)
      to relative lack of discrepancy (i.e. informant agreement; cross-situational):
      Moderate Parent/Low Teacher or Low Parent/Moderate Teacher Severity
      (Discrepancy), and Moderate or High Symptom Severity (Agreement). Subgroups were
      highly distinct (mean probability of group assignment = 94%). Relative to
      Discrepancy subgroups, Agreement subgroups were more likely to receive
      psychotropic medication, school-based special education services, and an ADOS-2
      diagnosis. These differential associations would not have been identified based
      solely on CASI-4R scores from one informant. CONCLUSIONS: The degree of parent
      teacher discrepancy about ASD symptom severity appears to provide more clinically
      useful information than reliance on a specific symptom domain or informant, and
      thus yields an innovative, cost-effective approach to assessing functional
      impairment. This conclusion stands in contrast to existing symptom clustering
      approaches in ASD, which treat within-informant patterns of symptom severity as
      generalizable across settings. Within-child variability in symptom expression
      across settings may yield uniquely useful information for characterizing the ASD
      phenotype.

PMID- 28449248
TI  - Betanodavirus: Dissection of the viral life cycle.
AB  - Progressive research has been recently made in dissecting the molecular biology
      of Betanodavirus life cycle, the causative pathogen of viral encephalopathy and
      retinopathy in economic important marine fish species. Establishment of
      betanodavirus infectious clone allows the manipulation of virus genome for
      functional genomic study, which elucidates the biological event of the viral life
      cycle at molecular level. The betanodavirus strategizes its replication by
      expressing anti-apoptosis/antinecrotic proteins to maintain the cell viability
      during early infection. Subsequently utilizes and controls the biological
      machinery of the infected cells for viral genome replication. Towards the late
      phase of infection, mass production of capsid protein for virion assembly induces
      the activation of host apoptosis pathway. It eventually leads to the cell lysis
      and death, which the lysis of cell contributes to the accomplishment of viral
      shedding that completes a viral life cycle. The recent efforts to dissect the
      entire betanodavirus life cycle are currently reviewed.

PMID- 28449249
TI  - T2 -Mapping evaluation of early cartilage alteration of talus for chronic lateral
      ankle instability with isolated anterior talofibular ligament tear or combined
      with calcaneofibular ligament tear.
AB  - PURPOSE: To quantitatively evaluate the cartilage alteration of talus for chronic
      lateral ankle instability (LAI) with isolated anterior talofibular ligament
      (ATFL) tear and combined ATFL and calcaneofibular ligament (CFL) tear using T2 
      mapping at 3.0T. MATERIALS AND METHODS: In all, 27 patients including 17 with
      isolated ATFL tear and 10 with ATFL+CFL tear, and 21 healthy subjects were
      recruited. All participants underwent T2 -mapping scan at 3T and patients
      completed American Orthopaedic Foot and Ankle Society (AOFAS) scoring. The total
      talar cartilage (TTC) was segmented into six compartments: medial anterior (MA),
      medial center (MC), medial posterior (MP), lateral anterior (LA), lateral center
      (LC), and lateral posterior (LP). The T2 value of each compartment was measured
      from T2 -mapping images. Data were analyzed with one-way analysis of variance
      (ANOVA), Student's t-test, and Pearson's correlation coefficient. RESULTS: The T2
      values of MA, MC, MP, TTC in the ATFL group and MA, MC, MP, LC, LP, TTC in the
      ATFL+CFL group were higher than those in the control group (P < 0.05). Moreover,
      the T2 values of MC, MP, LC, and TTC in the ATFL+CFL group were higher than those
      in the ATFL group (P < 0.05). The T2 values of MA in both patient groups were
      negatively correlated with AOFAS scores (r = -0.596, r = -0.690, P < 0.05).
      CONCLUSION: Chronic LAI with ATFL tear had a trend of increasing cartilage T2
      values in talar trochlea, mainly involving medial cartilage compartments. Chronic
      LAI with ATFL+CFL tear might result in higher T2 values in a much larger
      cartilage region than with ATFL tear. MA could be the main cartilage compartment
      that may affect the patient's clinical symptoms. LEVEL OF EVIDENCE: 1 Technical
      Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:69-77.

PMID- 28449250
TI  - Self-assembly of peptide boroxoles on cis-dihydroxylated oligoamide templates in
      water.
AB  - We develop templates that can be used to stabilize consistent oligomers of a
      bioactive peptide. In the present study, we synthesize oligomers of an antibody
      epitope from the amyloidogenic prion protein. Dynamic covalent chemistry is the
      basis for the spontaneous condensation of 2, 3, 4 or 6 peptides with qualified
      polyol templates presenting the required number of bioorthogonal ligation sites.
      To study this process in aqueous solution, the N-terminal amino acid of a 13-mer
      peptide is first acylated with 4-carboxy-benzoboroxole (1-hydroxy-1,3
      dihydrobenzo[c][1,2] oxaborole-5-carboxylic acid) and then mixed with the
      template to obtain self-assembled miniamyloids of specified degree of
      oligomerization. The template is assembled from bicyclic dipeptides of
      alternating d- and l-stereochemistry. The cis-diol group of this dipeptide
      hot=Tap (hot: d-hydroxythreonine, Tap: l-thiaproline) has sufficiently high
      affinity for boroxoles in water. A single N3 -hot=Tap-OMe dipeptide template
      forms a 1 : 1 complex with 4-carboxy-benzoboroxole with excellent
      diastereoselectivity. The oligomeric template N3 -(hot=Tap)n -OMe (n = 2, 3, 4 or
      6) presents a regular pattern of 2, 3, 4 or 6 cis-diol groups for the spontaneous
      esterification with the same number of boronic acids. Nuclear magnetic resonance
      identifies the homogenous regioselectivity and stereoselectivity of this ligation
      process. The combination of electron-poor benzoboroxoles with this optimized cis
      diol template allows for the complete ligation under high-dilution conditions in
      water with only 1.3 equivalents of peptide-boroxole per diol functionality.
      Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.

PMID- 28449251
TI  - Vascular twin nevi.
AB  - Vascular twin nevi (VTN) are characterized by the simultaneous dermatological
      manifestatiton of a telangiectatic naevus close to a nevus anemicus. Nevus
      anemicus (NA) is a vascular anomaly characterized by localized pale patches with
      normal melanine and melanocyte level. According to twin spotting phenomenon
      crossing-over in heterozygous somatic-cells during mitosis results in two
      different offspring homozygous cells. Consequent to this mechanism, two different
      vascular anomalies may occur at the same region. We present a patient with VTN
      and NA combination which we think serves as an example for a rare twin spotting
      phenomenon in the literature.

PMID- 28449252
TI  - Serum phosphorus levels and fracture following renal transplantation.
AB  - PURPOSE: Increased fracture rates are observed in renal transplant recipients
      (RTRs) compared with the general population. Risk factors include age, diabetes,
      dialysis vintage, immunosuppression and mineral and bone disorders.1 Low serum
      phosphorus levels occur post-transplantation; however, its relationship with
      fracture risk has not been evaluated. The purpose of this study was to evaluate
      risk factors for fracture in RTRs at a single tertiary referral centre. METHODS:
      A retrospective cross-sectional analysis of 146 patients (75 M, 71 F) who had
      been referred for dual energy X-ray densitometry (DXA) post-renal transplantation
      was performed. Aetiology of end stage kidney disease (ESKD), duration of
      dialysis, parathyroidectomy history, immunosuppression regimen, bone mineral
      density (BMD), biochemistry and fractures were documented. Statistical analyses
      included univariable and multivariable regression. RESULTS: The mean age of
      patients was 54 years and mean time post-transplantation 6.7 years. A total of 79
      fractures occurred in 52 patients (35%), with 40 fractures occurring post
      transplantation. Ankle/foot fractures were most common (48%). Lower serum
      phosphorus levels and declining femoral neck (FN) T-score and were associated
      with fractures in both univariable and multivariable regression analyses after
      adjusting for age, gender, weight, estimated glomerular filtration rate and pre
      transplant history of fracture (P=.011 and P=.042 respectively). The relationship
      between serum phosphorus and fracture remained significant independent of FN T
      score, parathyroid hormone levels, parathyroidectomy status and prednisolone use.
      CONCLUSION: Fracture was common post-renal transplantation. Lower serum
      phosphorus levels and declining FN T-scores were associated with fractures. The
      mechanism of this previously unreported observation requires further evaluation
      in prospective studies.

PMID- 28449253
TI  - Amide-Directed C-H Sodiation by a Sodium Hydride/Iodide Composite.
AB  - A new protocol for amide-directed ortho and lateral C-H sodiation is enabled by
      sodium hydride (NaH) in the presence of either sodium iodide (NaI) or lithium
      iodide (LiI). The transient organosodium intermediates could be transformed into
      functionalized aromatic compounds.

PMID- 28449254
TI  - Bioresorbable Fe-Mn and Fe-Mn-HA Materials for Orthopedic Implantation: Enhancing
      Degradation through Porosity Control.
AB  - Resorbable, porous iron-manganese-hydroxyapatite biocomposites with suitable
      degradation rates for orthopedic applications are prepared using salt-leaching
      for the first time. These transient biomaterials have the potential to replace
      inert, permanent implants that can suffer from long-term complications, or have
      to be surgically removed, leaving an unfavorable void. Fe30Mn-10HA materials are
      newly developed to address inadequate resorption rates of degradable materials
      proposed for orthopedic environments in the past. In this study, controllable
      porosities with 300 um diameter pores are introduced into Fe30Mn alloys and
      Fe30Mn-10HA composites, which enhance tissue ingrowth. For the composites, a Ca2
      Mn7 O14 phase generated within the Fe30Mn matrix during the sintering process
      greatly increases degradability. The combination of this second phase and added
      porosity is found to contribute to increased bone-like apatite layer formation,
      mouse bone marrow mesenchymal stem cell attachment, and reduction of detrimental
      oxide layer flaking. Remarkably, after thirty days in vitro, there is a
      significant increase in degradation up to 0.82 +/- 0.04 mm per year for 30 wt%
      porous Fe30Mn-10HA biocomposites, compared to 0.02 +/- 0.00 mm per year for
      traditional nonporous Fe30Mn, thereby increasing the viability of these materials
      for future clinical studies.

PMID- 28449256
TI  - Commentary on: Behera C, Rautjl R, Kumar R, Pooniya S, Sharma P, Gupta SK. Double
      hanging with single ligature: an unusual method in suicide pact. J Forensic Sci
      2017;62(1):265-6.

PMID- 28449257
TI  - The Development and Application of Random Match Probabilities to Firearm and
      Toolmark Identification.
AB  - The field of firearms and toolmark analysis has encountered deep scrutiny of
      late, stemming from a handful of voices, primarily in the law and statistical
      communities. While strong scrutiny is a healthy and necessary part of any
      scientific endeavor, much of the current criticism leveled at firearm and
      toolmark analysis is, at best, misinformed and, at worst, punditry. One of the
      most persistent criticisms stems from the view that as the field lacks quantified
      random match probability data (or at least a firm statistical model) with which
      to calculate the probability of a false match, all expert testimony concerning
      firearm and toolmark identification or source attribution is unreliable and
      should be ruled inadmissible. However, this critique does not stem from the hard
      work of actually obtaining data and performing the scientific research required
      to support or reject current findings in the literature. Although there are sound
      reasons (described herein) why there is currently no unifying probabilistic model
      for the comparison of striated and impressed toolmarks as there is in the field
      of forensic DNA profiling, much statistical research has been, and continues to
      be, done to aid the criminal justice system. This research has thus far shown
      that error rate estimates for the field are very low, especially when compared to
      other forms of judicial error. The first purpose of this paper is to point out
      the logical fallacies in the arguments of a small group of pundits, who advocate
      a particular viewpoint but cloak it as fact and research. The second purpose is
      to give a balanced review of the literature regarding random match probability
      models and statistical applications that have been carried out in forensic
      firearm and toolmark analysis.

PMID- 28449258
TI  - Improve Toolmarks' Impressions in Soft Wax.
AB  - When the forensic toolmarks laboratory receives for examination and comparison a
      tool that is suspected of having been involved in a crime, the expert performs
      tests designed to determine whether or not the specific tool generates the same
      toolmarks as those found at the crime scene. This is performed by testing tool
      striation on a piece of soft metal, such as lead, and examining the marks left by
      the tool. Studies have shown that wax may be an optimal material for this
      purpose. This study examines the use of wax at different temperatures and shows
      that quality of results is better when the wax is cooled (recommended temperature
      is -18 degrees C). At this temperature, the wax is flexible enough but does not
      smear and is not sticky. This makes the obtained marks clearer and of better
      quality.

PMID- 28449260
TI  - Commentary on: Shapiro S, Rotter M. Graphic depictions: portrayals of mental
      illness in video games. J Forensic Sci 2016;61(6):1592-5.

PMID- 28449259
TI  - Commentary on: Zhou C, Yool AJ, Byard RW. Armanni-Ebstein lesions in terminal
      hyperglycemia. J Forensic Sci doi: 10.1111/1556-4029.13360. Epub 2016 Dec 16.

PMID- 28449261
TI  - Exploring uncertainty of Amazon dieback in a perturbed parameter Earth system
      ensemble.
AB  - The future of the Amazon rainforest is unknown due to uncertainties in projected
      climate change and the response of the forest to this change (forest resiliency).
      Here, we explore the effect of some uncertainties in climate and land surface
      processes on the future of the forest, using a perturbed physics ensemble of
      HadCM3C. This is the first time Amazon forest changes are presented using an
      ensemble exploring both land vegetation processes and physical climate feedbacks
      in a fully coupled modelling framework. Under three different emissions
      scenarios, we measure the change in the forest coverage by the end of the 21st
      century (the transient response) and make a novel adaptation to a previously used
      method known as "dry-season resilience" to predict the long-term committed
      response of the forest, should the state of the climate remain constant past
      2100. Our analysis of this ensemble suggests that there will be a high chance of
      greater forest loss on longer timescales than is realized by 2100, especially for
      mid-range and low emissions scenarios. In both the transient and predicted
      committed responses, there is an increasing uncertainty in the outcome of the
      forest as the strength of the emissions scenarios increases. It is important to
      note however, that very few of the simulations produce future forest loss of the
      magnitude previously shown under the standard model configuration. We find that
      low optimum temperatures for photosynthesis and a high minimum leaf area index
      needed for the forest to compete for space appear to be precursors for dieback.
      We then decompose the uncertainty into that associated with future climate change
      and that associated with forest resiliency, finding that it is important to
      reduce the uncertainty in both of these if we are to better determine the
      Amazon's outcome.

PMID- 28449262
TI  - Predictive mechanisms linking brain opioids to chronic pain vulnerability and
      resilience.
AB  - : Chronic pain is a major global healthcare problem that is currently
      inadequately treated. In addition, the current use of opioids for treatment has
      reached far beyond the paucity of evidence for long-term benefits relative to
      risks. Benefit-risk models for opioid and non-opioid treatments would benefit
      from a rational, mechanism-based understanding of neuroplastic and neurochemical
      contributions to chronic pain. Here, we evaluate the findings and limitations of
      representative research investigating brain neuroplasticity and neurochemistry in
      chronic pain. In sum, the mechanisms of pain-related neuroplasticity in the brain
      remain poorly understood because neuroimaging studies have been largely
      descriptive. We argue that definition is needed of optimal (pain-resilient) and
      suboptimal (pain-vulnerable) functioning of the endogenous opioid system in order
      to identify neurochemical contributions to aberrant neuroplasticity in chronic
      pain. We outline the potential benefits of computational approaches that utilize
      evolutionary and statistical optimality principles, illustrating this approach
      with mechanistic hypotheses on opioid function. In particular, we discuss the
      role of predictive mechanisms in perceptual and associative plasticity and
      evidence for their modulation by endogenous opioids. Future research should
      attempt to utilize formal computational models to provide evidence for the
      clinical validity of this approach, thereby providing a rational basis for future
      treatment and, ideally, prevention. LINKED ARTICLES: This article is part of a
      themed section on Emerging Areas of Opioid Pharmacology. To view the other
      articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.

PMID- 28449264
TI  - Macroscopically Oriented Porous Materials with Periodic Ordered Structures: From
      Zeolites and Metal-Organic Frameworks to Liquid-Crystal-Templated Mesoporous
      Materials.
AB  - Porous materials with molecular-sized periodic structures, as exemplified by
      zeolites, metal-organic frameworks, or mesoporous silica, have attracted
      increasing attention due to their range of applications in storage, sensing,
      separation, and transformation of small molecules. Although the components of
      such porous materials have a tendency to pack in unidirectionally oriented
      periodic structures, such ideal types of packing cannot continue indefinitely,
      generally ceasing when they reach a micrometer scale. Consequently, most porous
      materials are composed of multiple randomly oriented domains, and overall behave
      as isotropic materials from a macroscopic viewpoint. However, if their channels
      could be unidirectionally oriented over a macroscopic scale, the resultant porous
      materials might serve as powerful tools for manipulating molecules. Guest
      molecules captured in macroscopically oriented channels would have their
      positions and directions well-defined, so that molecular events in the channels
      would proceed in a highly controlled manner. To realize such an ideal situation,
      numerous efforts have been made to develop various porous materials with
      macroscopically oriented channels. An overview of recent studies on the
      synthesis, properties, and applications of macroscopically oriented porous
      materials is presented.

PMID- 28449263
TI  - multi-dice: r package for comparative population genomic inference under
      hierarchical co-demographic models of independent single-population size changes.
AB  - Population genetic data from multiple taxa can address comparative
      phylogeographic questions about community-scale response to environmental shifts,
      and a useful strategy to this end is to employ hierarchical co-demographic models
      that directly test multi-taxa hypotheses within a single, unified analysis. This
      approach has been applied to classical phylogeographic data sets such as
      mitochondrial barcodes as well as reduced-genome polymorphism data sets that can
      yield 10,000s of SNPs, produced by emergent technologies such as RAD-seq and GBS.
      A strategy for the latter had been accomplished by adapting the site frequency
      spectrum to a novel summarization of population genomic data across multiple taxa
      called the aggregate site frequency spectrum (aSFS), which potentially can be
      deployed under various inferential frameworks including approximate Bayesian
      computation, random forest and composite likelihood optimization. Here, we
      introduce the r package multi-dice, a wrapper program that exploits existing
      simulation software for flexible execution of hierarchical model-based inference
      using the aSFS, which is derived from reduced genome data, as well as
      mitochondrial data. We validate several novel software features such as applying
      alternative inferential frameworks, enforcing a minimal threshold of time
      surrounding co-demographic pulses and specifying flexible hyperprior
      distributions. In sum, multi-dice provides comparative analysis within the
      familiar R environment while allowing a high degree of user customization, and
      will thus serve as a tool for comparative phylogeography and population genomics.

PMID- 28449266
TI  - Frailty as a Predictor of Future Fracture in Older Adults: A Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: Studies have identified frailty as an effective predictor of
      fracture; however, the correlation between frailty and fracture differs between
      various stages of frailty. OBJECTIVES: The main aim is to determine the
      correlation between various stages of frailty and fracture risk; a secondary
      purpose is to determine the correlation between subgroups (e.g., females, females
      with a hip fracture, or aged 65 years or older) within the stages of frailty and
      fracture risk. Finally, effect of frailty criteria on the association between
      stages of frailty and fracture risk was tested. METHODS: We conducted a
      systematic review and meta-analysis. The inclusion criteria were as follows: (a)
      a prospective study design; (b) subjects aged 55 years or older; (c) a division
      into robust, prefrail, and frail groups; and (d) reported confidence intervals of
      hazard ratio. Two investigators independently assessed quality and discussed
      their findings to reach consensus. The quality of the literature was assessed and
      the level of evidence was also determined. RESULTS: In total, five studies
      included 103,783 older people and recorded 2,960 fractures. The results
      identified that the risk of fracture in the frail people was higher than that in
      both the robust people (summary HR: 1.67; 95% CI [1.46-1.91]) and prefrail people
      (summary HR: 1.28; 95% CI [1.16-1.40], and that the risk of fracture in the
      prefrail people was higher than that in the robust people (summary HR: 1.30; 95%
      CI [1.20-1.41]). A subgroup analysis revealed that among female adults, older
      females with hip fracture, or those aged 65 years or more, those who were
      categorized as frail showed the highest fracture risk, followed by those who were
      categorized as prefrail. LINKING EVIDENCE TO ACTION: Professional nurses caring
      for frail or prefrail people should actively develop fracture prevention measures
      to reduce the risk of death caused by fractures.

PMID- 28449265
TI  - A pilot study of nocturnal temporalis muscle activity in TMD diagnostic groups of
      women.
AB  - Temporomandibular disorder (TMD) incidences are believed to be related to
      parafunctional behaviours like teeth clenching. This pilot study aimed to (i)
      develop an automated clench-detection algorithm, and (ii) apply the algorithm to
      test for differences in nocturnal clenching in women with and without TMD.
      Subjects gave informed consent to participate. Adult women were categorised using
      Diagnostic Criteria for TMD according to presence/absence (+/-) of both TM joint
      disc placement (DD) and chronic pain (P) into two groups (+DD+P, -DD-P) with 12
      subjects each. Surface temporalis electromyography was recorded during oral tasks
      performed by subjects at two laboratory sessions. The data were used to
      characterise muscle activity per N of bite force (MUV/N) for each subject,
      develop the clench-detection algorithm and test its accuracy. Ambulatory surface
      temporalis electromyography was self-recorded by each subject over three nights
      and analysed using the algorithm and bite force (N) versus muscle activity MUV/N
      calibrations. Bonferroni-adjusted homoscedastic t-tests assessed for significant
      between-group differences in clenching (P < 0.05). Sensitivity, specificity and
      accuracy of algorithm-detected laboratory clenches were all >=96%. During self
      recordings 95% of clenches had durations of <4 s and peak forces of <10 N in both
      groups. Mean clench durations were significantly longer (P = 0.042) in +DD+P (1.9
      +/- 0.8 s) than -DD-P subjects (1.4 +/- 0.4 s). Mean temporalis duty factors
      (%clench time/total recording time) were significantly larger (P = 0.041) in
      +DD+P (0.47 +/- 0.34%) than -DD-P (0.26 +/-0.22%) subjects. Nocturnal temporalis
      muscle activities detected by a validated algorithm were longer per clench and
      recording time in +DD+P compared to -DD-P women.

PMID- 28449268
TI  - Ventral, but not dorsal, hippocampus inactivation impairs reward memory
      expression and retrieval in contexts defined by proximal cues.
AB  - The hippocampus (HPC) has been widely implicated in the contextual control of
      appetitive and aversive conditioning. However, whole hippocampal lesions do not
      invariably impair all forms of contextual processing, as in the case of complex
      biconditional context discrimination, leading to contention over the exact nature
      of the contribution of the HPC in contextual processing. Moreover, the
      increasingly well-established functional dissociation between the dorsal (dHPC)
      and ventral (vHPC) subregions of the HPC has been largely overlooked in the
      existing literature on hippocampal-based contextual memory processing in
      appetitively motivated tasks. Thus, the present study sought to investigate the
      individual roles of the dHPC and the vHPC in contextual biconditional
      discrimination (CBD) performance and memory retrieval. To this end, we examined
      the effects of transient post-acquisition pharmacological inactivation (using a
      combination of GABAA and GABAB receptor agonists muscimol and baclofen) of
      functionally distinct subregions of the HPC (CA1/CA3 subfields of the dHPC and
      vHPC) on CBD memory retrieval. Additional behavioral assays including novelty
      preference, light-dark box and locomotor activity test were also performed to
      confirm that the respective sites of inactivation were functionally silent. We
      observed robust deficits in CBD performance and memory retrieval following
      inactivation of the vHPC, but not the dHPC. Our data provides novel insight into
      the differential roles of the ventral and dorsal HPC in reward contextual
      processing, under conditions in which the context is defined by proximal cues.

PMID- 28449267
TI  - Evaluation of the utility of 99m Tc-MDP bone scintigraphy versus MIBG
      scintigraphy and cross-sectional imaging for staging patients with neuroblastoma.
AB  - PURPOSE: Accurate staging of neuroblastoma requires multiple imaging
      examinations. The purpose of this study was to determine the relative
      contribution of 99m Tc-methylene diphosphonate (MDP) bone scintigraphy (bone
      scan) versus metaiodobenzylguanidine scintigraphy (MIBG scan) for accurate
      staging of neuroblastoma. METHODS: A medical record search by the identified
      patients with neuroblastoma from 1993 to 2012 who underwent both MIBG and bone
      scan for disease staging. Cross-sectional imaging was used to corroborate the
      scintigraphy results. Clinical records were used to correlate imaging findings
      with clinical staging and patient management. RESULTS: One hundred thirty-two
      patients underwent both MIBG and bone scan for diagnosis. All stage 1 (n = 12), 2
      (n = 8), and 4S (n = 4) patients had a normal bone scan with no skeletal MIBG
      uptake. Six of 30 stage 3 patients had false (+) bone scans. In the 78 stage 4
      patients, 58/78 (74%) were both skeletal MIBG(+)/bone scan (+). In 56 of the 58
      cases, skeletal involvement detected with MIBG was equal to or greater than that
      detected by bone scan. Only 3/78 had (-) skeletal MIBG uptake and (+) bone scans;
      all 3 had other sites of metastatic disease. Five of 78 had (+) skeletal MIBG
      with a (-) bone scan, while 12/78 had no skeletal involvement by either MIBG or
      bone scan. In no case did a positive bone scan alone determine a stage 4
      designation. CONCLUSION: In the staging of neuroblastoma, 99m Tc-MDP bone
      scintigraphy does not identify unique sites of disease that affect disease stage
      or clinical management, and in the majority of cases bone scans can be omitted
      from the routine neuroblastoma staging algorithm.

PMID- 28449269
TI  - Real-world impact of a quality improvement project to implement rapid rule out of
      acute coronary syndrome processes in eligible emergency department patients.

PMID- 28449270
TI  - Strong association between cardiorespiratory fitness and serum lipoprotein
      subclass pattern in prepubertal healthy children.
AB  - This study reveals the lipoprotein subclass pattern associated with
      cardiorespiratory fitness (CRF) in healthy children. Serum concentrations of
      lipoprotein subclasses and concentrations and average particle size of their main
      classes were quantified in 94 ethnic Norwegian children using high-performance
      liquid chromatography (HPLC). Twenty-four lipoprotein features were used as input
      to multivariate regression analysis with CRF measured either by peak oxygen
      consumption (VO2peak) using a continuous treadmill protocol or indirectly by the
      10-minute Andersen intermittent running field test. By including BMI and gender
      as descriptors, a predictive cross-validated multivariate regression model was
      obtained for both CRF measures. CRF correlated positively with average particle
      size for high-density lipoprotein (HDL) and its subclasses of large HDL particles
      and negatively with very small HDL particles, chylomicrons, triglycerides, and
      average size and concentration of very low-density lipoprotein (VLDL) particles
      and VLDL subclasses of large particles (P<.05). BMI correlated negatively with
      both measures of CRF, but exhibited a stronger association with VO2peak than with
      the Andersen test. Our data showed a strong association between CRF measured
      either by VO2peak or by the Andersen test and a subclass lipoprotein pattern that
      is associated with cardiovascular (CV) health. Thus, our results show why high
      levels of CRF are beneficial for children's CV health. The Andersen test, being a
      practical field test that involves minimal equipment and, being less influenced
      by BMI than VO2peak, represents a good measure of CRF, and, accordingly, a proxy
      measure of cardiovascular health status in children.

PMID- 28449272
TI  - Adalimumab is a safe option for psoriasis patients with concomitant hepatitis B
      or C infection: a multicentre cohort study of 37 patients and review of the
      literature. Reply to Dr. Ricceri letter.

PMID- 28449271
TI  - Delusional and psychotic disorders in juvenile myotonic dystrophy type-1.
AB  - We investigated the clinically derived hypothesis of a relatively high incidence
      of delusional and psychotic disorders in adolescents with juvenile Myotonic
      Dystrophy type-1 (DM1). Twenty-seven subjects of age 16-25 with juvenile DM1 and
      their parents were invited to have a clinical psychiatric interview, and to
      complete an ASEBA behavior checklist (YSR, ASR, CBCL, and ABCL). We diagnosed a
      Delusional Disorder in 19% of our patients and a Psychotic Disorder not otherwise
      specified in another 19%. These two groups of patients had a significantly worse
      level of clinically defined general functioning. It is clinically relevant to
      investigate in patients with juvenile DM the symptom of delusions and the
      presence of a delusional and psychotic disorder, and to consider the presence of
      juvenile DM in youngsters presenting with such a thought disorder. These
      disorders compromise the general functioning of the subjects and are often to
      some extent treatable. (c) 2017 Wiley Periodicals, Inc.

PMID- 28449273
TI  - Systematic review: the safety of vedolizumab for the treatment of inflammatory
      bowel disease.
AB  - BACKGROUND: Vedolizumab specifically recognises the alpha4beta7 integrin and
      selectively blocks gut lymphocyte trafficking: potentially, it offers gut
      specific immunosuppression. AIM: To review the safety of vedolizumab and
      summarise post-marketing data to assess if any safety concerns that differ from
      registration trials have emerged. METHOD: A systematic bibliographic search
      identified six registration trials and nine cohort studies. RESULTS: Integrated
      data from registration trials included 2830 vedolizumab-exposed patients (4811
      person-years exposure [PYs]) and 513 placebo patients. This reported lower
      exposure-adjusted incidence rates of infection (63.5/100 PYs; 95% CI: 59.6-67.3)
      and serious adverse events (20.0/100 PYs; 95% CI: 18.5-21.5) compared to placebo
      (82.9/100 PYs; 95% CI: 68.3-97.5) and (28.3/100 PYs 95% CI: 20.6-35.9)
      respectively. Higher, but statistically insignificant rates of enteric infections
      occurred in vedolizumab-exposed patients (7.4/100 PYs; 95% CI: 6.6-8.3) compared
      to placebo (6.7 PYs; 95% CI: 3.2-10.1). Six post-marketing cohort studies (1049
      patients, 403 PYs) demonstrated rates of infection of 8% (82/1049); enteric
      infection of 2% (21/1049) and adverse events of 16% (166/1049). Multivariate
      analysis in one cohort study suggested increased risk of surgical site infection
      with perioperative VDZ. Human experience in pregnancy is limited. CONCLUSIONS:
      Post-marketing data confirm the excellent safety of vedolizumab observed in
      registration trials. The signal of post-operative complications should be
      interpreted with caution, but warrants further study. Although comparative
      studies are needed, Vedolizumab may be a safe alternative in patients who best
      avoid systematic immunosuppression, including those pre-disposed to infection,
      malignancy or the elderly.

PMID- 28449274
TI  - A DNA barcode library for Germany's mayflies, stoneflies and caddisflies
      (Ephemeroptera, Plecoptera and Trichoptera).
AB  - Mayflies, stoneflies and caddisflies (Ephemeroptera, Plecoptera and Trichoptera)
      are prominent representatives of aquatic macroinvertebrates, commonly used as
      indicator organisms for water quality and ecosystem assessments. However,
      unambiguous morphological identification of EPT species, especially their
      immature life stages, is a challenging, yet fundamental task. A comprehensive DNA
      barcode library based upon taxonomically well-curated specimens is needed to
      overcome the problematic identification. Once available, this library will
      support the implementation of fast, cost-efficient and reliable DNA-based
      identifications and assessments of ecological status. This study represents a
      major step towards a DNA barcode reference library as it covers for two-thirds of
      Germany's EPT species including 2,613 individuals belonging to 363 identified
      species. As such, it provides coverage for 38 of 44 families (86%) and
      practically all major bioindicator species. DNA barcode compliant sequences
      (>=500 bp) were recovered from 98.74% of the analysed specimens. Whereas most
      species (325, i.e., 89.53%) were unambiguously assigned to a single Barcode Index
      Number (BIN) by its COI sequence, 38 species (18 Ephemeroptera, nine Plecoptera
      and 11 Trichoptera) were assigned to a total of 89 BINs. Most of these additional
      BINs formed nearest neighbour clusters, reflecting the discrimination of
      geographical subclades of a currently recognized species. BIN sharing was
      uncommon, involving only two species pairs of Ephemeroptera. Interestingly, both
      maximum pairwise and nearest neighbour distances were substantially higher for
      Ephemeroptera compared to Plecoptera and Trichoptera, possibly indicating older
      speciation events, stronger positive selection or faster rate of molecular
      evolution.

PMID- 28449275
TI  - Public perception of dermatology and dermatologists in Italy: results from a
      population-based national survey.
AB  - INTRODUCTION: The public perception of dermatology and dermatologists may be very
      relevant in guiding strategies for improving dermatologic care but it has been
      poorly investigated in Europe. OBJECTIVE: To investigate the public's perception
      of dermatology and dermatologists in Italy. METHODS: A representative sampling of
      Italian adults (n = 1500, aged 18-70 years), residing throughout the national
      territory was interviewed through a population-based telephone survey using a
      structured questionnaire. RESULTS: The majority of interviewed aged between 35
      and 54 years (45%) and had an intermediate educational level (57%), were employed
      (56%), and had at least one child in the family (68%). 70% of the interviewed
      knew at least one skin disease, particularly psoriasis, dermatitis, urticaria,
      skin tumours and nevi. The general practitioner resulted to be the first
      healthcare provider to consult in the case of skin problems for 73% of surveyed,
      with only 27% referring directly the private dermatologist. The dermatologist was
      the main referral specialist for psoriasis, pruritus and skin tumours by 66%, 54%
      and 53% of the sample, respectively. The most common reason for dermatological
      consultation was the control of nevi. In the case of childhood dermatitis, 52%
      indicated the paediatrician and 38% the dermatologist as the reference
      specialist. Almost half of the surveyed turned out to have a trusted
      dermatologist to consult in the case of skin problems. Finally, among those
      visited at least one time by a dermatologist, 46% were promoters, that is, they
      would recommend their dermatologist to a friend (net promoter score, 27).
      CONCLUSIONS: The general population has a wide-ranging understanding of skin
      diseases and the central role of dermatologists in skin care. Patients are
      looking for technical competence and loyalty, because this lead to more trusted
      and satisfactory physician-patient relationship. Public campaigns may be relevant
      in increasing awareness on curability of common skin diseases.

PMID- 28449276
TI  - The efficacy of thrombolysis in lacunar stroke - evidence from the Austrian
      Stroke Unit Registry.
AB  - BACKGROUND AND PURPOSE: Intravenous thrombolysis (ivT) with recombinant tissue
      plasminogen activator is established in acute ischaemic stroke. Little is known,
      however, about its efficacy in different stroke subtypes. METHODS: A
      retrospective analysis of 128 733 patients from the Austrian Stroke Unit Registry
      was performed. Patients were classified as lacunar (LacS) or non-lacunar
      ischaemic stroke (nonLacS) by use of the clinical syndrome and technical
      findings. Outcome parameters were the short term improvement in the stroke unit
      [the difference of the National Institutes of Health Stroke Scale (NIHSS) score
      at admission and at discharge] and the modified Rankin Scale (mRS) score at 3
      months. Patients were assigned to four groups according to thrombolysis and
      stroke subtype. To control for confounding, patients were matched for variables
      identified with impact outcome and for variables of general interest (NIHSS at
      admission, mRS before stroke and general risk factors). RESULTS: There were four
      matched groups of 401 cases each. In LacS median short term improvement was 3
      [interquartile range (IQR) 2-5] NIHSS points in the thrombolysed patients and 2
      (IQR 1-4) in the non-thrombolysed patients (P < 0.001). In the nonLacS groups
      median short term improvement was 3 (IQR 1-5) in the thrombolysed and 2 (IQR 0-4)
      in the non-thrombolysed patients (P < 0.001). At 3-month follow-up, ivT was
      significantly associated with a better functional outcome in LacS (P < 0.001) and
      nonLacS patients (P < 0.001). Taking magnetic resonance imaging as a requirement
      for stroke subtyping led to similar results. CONCLUSIONS: Patients with both
      lacunar and non-lacunar stroke benefitted from ivT. The degree of improvement was
      similar in both groups.

PMID- 28449277
TI  - Expertise shapes domain-specific functional cerebral asymmetry during mental
      imagery: the case of culinary arts and music.
AB  - Mental imagery in experts has been documented in visual arts, music and dance.
      Here, we examined this issue in an understudied art domain, namely, culinary
      arts. Previous research investigating mental imagery in experts has reported
      either a stronger involvement of the right hemisphere or bilateral brain
      activation. The first aim of our study was to examine whether culinary arts also
      recruit such a hemispheric pattern specifically during odor mental imagery. In a
      second aim, we investigated whether expertise effects observed in a given sensory
      domain transfer to another modality. We combined psychophysics and
      neurophysiology to study mental imagery in cooks, musicians and controls. We
      collected response times and event-related potentials (ERP) while participants
      mentally compared the odor of fruits, the timbre of musical instruments and the
      size of fruits, musical instruments and manufactured objects. Cooks were faster
      in imagining fruit odors, and musicians were faster in imagining the timbre of
      musical instruments. These differences were not observed in control participants.
      This expertise effect was reflected in the ERP late positive complex (LPC): only
      experts showed symmetric bilateral activation, specifically when cooks imagined
      odors and when musicians imagined timbres. In contrast, the LPC was significantly
      greater in the left hemisphere than in the right hemisphere for non-expert
      participants in all conditions. These findings suggest that sensory expertise
      does not involve transfer of mental imagery ability across modalities and
      highlight for the first time that olfactory expertise in cooks induces a balance
      of activations between hemispheres as does musical expertise in musicians.

PMID- 28449278
TI  - Seroepidemiology and molecular characterization of hepatitis E virus infection in
      swine and occupationally exposed workers in Punjab, India.
AB  - Hepatitis E virus (HEV) has two discrete epidemiological patterns: waterborne
      epidemics in developing countries only, caused by HEV genotype I, and sporadic
      zoonotic outbreaks in developing and developed countries caused by genotypes III
      and IV. This study was designed to investigate seroprevalence, molecular
      detection and the characterization of HEV by nested RT-PCR in swine as well as
      the occupational risk to exposed human population in Punjab state of north
      western India. The occupational risk-exposed group comprised of swine farmers
      (organized - mixed feed feeders and unorganized - swill feeders), slaughterhouse
      workers, sewage workers and veterinary internes. During the study period, blood
      and faecal samples were collected from 320 swine and 360 humans with both high
      and low occupational exposure risks. The overall seroprevalence of swine HEV was
      65.00%, with a significantly higher seropositivity in growing pigs (2-8 months of
      age). The prevalence of HEV RNA in swine faecal samples by nRT-PCR was 8.75% with
      a significantly higher detection in swill-fed pigs. With humans in the high
      occupational exposure risk population, significantly higher anti-HEV IgG
      seropositivity was observed (60.48%) as compared to control population (10.71%).
      Strong evidence of association between human anti-HEV IgG seropositivity and
      certain occupational exposure risk groups was observed (p < 0.05). This indicates
      that unorganized swine farmers, slaughterhouse workers and sewage workers have
      higher odds of HEV infection in this study region. Percentage of nucleotide
      similarity between swine and human HEV isolates was less than that found in
      countries with zoonotic HEV outbreaks. Molecular characterization revealed the
      circulation of G IV and G I genotypes among swine and human population in Punjab
      state, respectively.

PMID- 28449279
TI  - Review of the strengths and difficulties questionnaire translated into languages
      spoken by children and adolescents of refugee background.
AB  - The Strengths and Difficulties Questionnaire (SDQ), routinely used to screen for
      children's and adolescents' emotional and behavioural problems, has been
      translated into at least 80 languages. As children of refugee background are
      particularly vulnerable to mental health problems resulting from their refugee
      experiences, this review examines whether SDQs translated into languages spoken
      by major refugee groups are validated and culturally equivalent to the original
      SDQ and sensitive to change following interventions. No reviewed studies of
      translated SDQs reported on challenges in achieving conceptual and linguistic
      equivalence in translation. Factor analysis predominantly showed structural
      inequivalence with the original 5-factor model, suggesting translated SDQ
      subscales may measure different constructs. Predictive equivalence findings
      tended to show somewhat higher sensitivity for detecting disorder than the
      original SDQ's low sensitivity, and somewhat lower specificity. Outcome studies
      yielded equivocal results with refugee and immigrant groups. SDQ items do not
      detect the psychological sequelae of trauma; hence it is recommended that the SDQ
      be used with caution to screen refugee children, with a follow-up clinical
      interview for verification. Cross-cultural qualitative research is needed into
      parents' and adolescents' interpretation of translated SDQ items.

PMID- 28449280
TI  - A randomised controlled trial of placebo, droperidol or ondansetron to prevent
      nausea and vomiting after tonsillectomy in children receiving dexamethasone.
AB  - We tested whether prophylactic droperidol and ondansetron, in combination with a
      moderate dose of dexamethasone, were equally effective in reducing nausea and
      vomiting after tonsillectomy in children and that both were superior to saline
      with dexamethasone. We randomly allocated 300 children to intravenous saline,
      droperidol 10 MUg.kg-1 or ondansetron 150 MUg.kg-1 , after induction of
      anaesthesia and the administration of intravenous dexamethasone 250 MUg.kg-1 .
      The rates (95%CI) of nausea or vomiting within 24 postoperative hours were: 42/91
      after saline, 46% (36%-57%); 43/87 after droperidol, 49% (39%-60%); reduced to
      18/84 by ondansetron, 21% (13%-32%), p < 0.001. There were no differences in the
      rates of side-effects between groups. We conclude that ondansetron is more
      effective than saline in preventing nausea or vomiting after paediatric
      tonsillectomy when given with a moderate dose of dexamethasone, whereas
      droperidol was not.

PMID- 28449281
TI  - Effect of 0.5 mg versus 1 mg varenicline for smoking cessation: a randomized
      controlled trial.
AB  - AIMS: Varenicline is used in smoking cessation. The aims of the trial were to
      test for differences between standard 1- and 0.5-mg doses (both twice daily
      during 8 weeks) in (1) abstinence, (2) adherence and (3) side effects. DESIGN:
      Open-label randomized parallel-group controlled trial with 1-year follow-up. All
      those randomized were included in the final sample using an intention-to-treat
      (ITT) approach. SETTING: Stop-Smoking Clinic of the Virgen Macarena University
      Hospital in Seville, Spain. PARTICIPANTS: The study comprised smokers (n = 484),
      59.5% of whom were men with a mean age of 50.67 years and a smoking history of
      37.5 pack-years. INTERVENTION AND COMPARATOR: Participants were randomized to 1
      mg (n = 245) versus 0.5 mg (n = 239) and received behavioural support, which
      consisted of a baseline visit and six follow-ups during 1 year. MEASUREMENTS: The
      primary outcome was continuous self-reported abstinence during 1 year, with
      biochemical verification. The secondary outcomes were adherence and side effects.
      Also measured were baseline demographics, medical history and smoking
      characteristics. FINDINGS: Abstinence rates at 1 year were 46.5% with 1 mg versus
      46.4% with 0.5 mg [odds ratio (OR) = 0.997; 95% confidence interval (CI) = 0.7
      1.43; P = 1.0]; Bayes factor in favour of H0 = 238.507, Bayes factor against H0 =
      0.004. Treatment adherence was similar in both regimens (OR = 1.16; 95% CI = 0.8
      1.7; P = 0.44). Side effects were reported in 19.3% of cases with 1 mg versus
      12.1% with 0.5 mg, although with no significant differences between regimens (OR
      = 1.73; 95% CI = 0.94-3.18; P = 0.093). CONCLUSIONS: There appears to be no
      difference in smoking cessation effectiveness between 1 mg and 0.5 mg
      varenicline, both administered twice daily for 8 weeks, with similar rates of
      abstinence (46.5% versus 46.4%), adherence and side effects.

PMID- 28449282
TI  - Organotitania-Based Nanostructures as a Suitable Platform for the Implementation
      of Binary, Ternary, and Fuzzy Logic Systems.
AB  - Titanium dioxide nanocomposites were synthesized in hierarchical architectures
      through the use of a 1,4-dihydroxyanthraquinone photosensitizer. In the first
      step, the dye was either incorporated into the TiO2 core or adsorbed on its
      surface. In the subsequent phase, both structures were covered with an outer
      layer of titanium dioxide. The structure, morphology, aggregation, spectroscopic,
      and electrochemical properties of the synthesized TiO2 -based materials are
      presented with emphasis on the photosensitization and the photocurrent switching
      phenomena, which are also discussed within the context of the optical logic gates
      implementation and fuzzy logic systems operation. We present three different
      interpretations of the photocurrent action spectra yielding binary, ternary, or
      fuzzy logic circuits.

PMID- 28449283
TI  - Physiological responses of reared sea bream (Sparus aurata Linnaeus, 1758) to an
      Amyloodinium ocellatum outbreak.
AB  - Amyloodiniosis represents a major bottleneck for semi-intensive aquaculture
      production in Southern Europe, causing extremely high mortalities. Amyloodinium
      ocellatum is a parasitic dinoflagellate that can infest almost all fish,
      crustacean and bivalves that live within its ecological range. Fish mortalities
      are usually attributed to anoxia, associated with serious gill hyperplasia,
      inflammation, haemorrhage and necrosis in heavy infestations; or with
      osmoregulatory impairment and secondary microbial infections due to severe
      epithelial damage in mild infestation. However, physiological information about
      the host responses to A. ocellatum infestation is scarce. In this work, we
      analysed the proteome of gilthead sea bream (Sparus aurata) plasma and relate it
      with haematological and immunological indicators, in order to enlighten the
      different physiological responses when exposed to an A. ocellatum outbreak. Using
      2D-DIGE, immunological and haematological analysis and in response to the A.
      ocellatum contamination we have identified several proteins associated with acute
      phase response, inflammation, lipid transport, homoeostasis, and osmoregulation,
      wound healing, neoplasia and iron transport. Overall, this preliminary study
      revealed that amyloodiniosis affects some fish functional pathways as revealed by
      the changes in the plasma proteome of S. aurata, and that the innate
      immunological system is not activated in the presence of the parasite.

PMID- 28449284
TI  - Paediatric melanoma.
AB  - Paediatric melanoma, although rare, is the most common skin cancer in children.
      Our current knowledge on paediatric melanoma incidence trends is expanding, as
      several studies have addressed this issue with conflicting results. Known risk
      factors for paediatric melanoma include family history of melanoma, a previous
      history of malignancy, large congenital nevi, numerous melanocytic nevi,
      sunburns, increased UV exposure and a sun-sensitive phenotype. In younger
      children, melanoma more often presents with atypical features, such as a
      changing, amelanotic or uniformly coloured, often bleeding lesion, not fulfilling
      in most cases the conventional ABCDE criteria. The major differential diagnoses
      are melanocytic nevi, proliferative nodules in congenital nevi and atypical Spitz
      tumours. Moreover, in the younger age group non-Caucasian children are over
      represented, tumours tend to be thicker and lymph nodes are often involved.
      Despite the frequent diagnosis at an advanced stage, the overall survival is fair
      in paediatric melanoma. Specific guidelines for management of melanoma in
      children do not exist, and most often the disease is treated similarly to
      melanoma in adults.

PMID- 28449285
TI  - Research Review: Childhood chronic physical illness and adult emotional health -
      a systematic review and meta-analysis.
AB  - BACKGROUND: Childhood chronic physical illness is associated with a greater
      vulnerability for emotional problems (i.e. depression and anxiety) in childhood.
      However, little is known about life-long effects of childhood chronic physical
      illness on mental health. The present study aims to systematically review
      evidence for associations between eight chronic physical illnesses with childhood
      onset (arthritis, asthma, cancer, chronic renal failure, congenital heart
      disease, cystic fibrosis, type 1 diabetes, and epilepsy) and adult emotional
      problems. METHODS: A database search of MEDLINE, PsycARTICLES, PsycINFO, and
      ScienceDirect was undertaken, and random effects meta-analyses were used to
      synthesise evidence from eligible studies. RESULTS: In total, 37 studies were
      eligible for the systematic review (n = 45,733) and of these, 34 studies were
      included in the meta-analyses (n = 45,358). There were overall associations
      between childhood chronic physical illness and adult depression (OR = 1.31; 95%
      CI [1.12, 1.54]) and anxiety (OR = 1.47; 95% CI [1.13, 1.92]). Separate meta
      analyses for childhood asthma, type 1 diabetes and cancer were also conducted,
      with cancer being significantly associated with adult depression (OR = 1.19; 95%
      CI [1.00, 1.42]). CONCLUSIONS: The effects of childhood chronic physical illness
      on the risk of emotional problems persist beyond childhood and adolescence.
      Mental health prevention and intervention strategies targeting children with
      chronic physical illnesses can have long-term benefits.

PMID- 28449286
TI  - Full dilation cesarean section: a risk factor for recurrent second-trimester loss
      and preterm birth.
AB  - INTRODUCTION: A previous cesarean section at full dilation (FDCS) is a risk
      factor for preterm birth. To provide insight into the risk to subsequent
      pregnancies, this cohort study compares the outcomes of pregnant women with a
      previous preterm birth associated with either a prior FDCS or a prior term
      vaginal delivery. MATERIAL AND METHODS: We identified women attending two inner
      city preterm surveillance clinics (Guy's and St Thomas Hospital and University
      College London Hospital, London, UK) who had a spontaneous late miscarriage (14+0
      -23+6 weeks) or spontaneous preterm birth (sPTB; <37 weeks' gestation) following
      a term pregnancy, and then a further pregnancy for analysis. Cases were those
      with a prior term FDCS, whereas controls had a prior term vaginal birth; both
      before the late miscarriage/sPTB. Main outcomes were gestational age at delivery
      and delivery at <30 weeks in the next (third) pregnancy. RESULTS: Over the study
      period, 66 women were identified who had a term delivery followed by a late
      miscarriage or sPTB, and a subsequent pregnancy. Recurrent sPTB <30 weeks was
      more common in cases than in controls (12/29, vs. 5/37, p = 0.02, Fisher's exact
      test, RR 3.06, 95% CI 1.22-7.71). Median gestation at delivery was significantly
      lower [249 days (IQR 154, 267) vs. 280 days (IQR 259, 280) p < 0.001]. Eleven
      women in the FDCS group received vaginal cerclage, five of whom delivered <37
      weeks. CONCLUSION: In this cohort study we observed that women with a term FDCS
      and subsequent late miscarriage/sPTB have a higher risk of recurrent sPTB
      compared with women whose first term delivery was vaginal.

PMID- 28449287
TI  - A case of milium-like syringoma limited to the neck.

PMID- 28449288
TI  - Brain and lung metastasis secondary to metastatic atypical fibroxanthoma: A rare
      Australian case.

PMID- 28449289
TI  - Corrigendum.

PMID- 28449290
TI  - Oral mucocoeles in chronic graft-versus-host-disease: report of a case following
      lung transplantation.

PMID- 28449291
TI  - Consumer and carer perspectives in the development of a mental health research,
      treatment and teaching facility: A thematic analysis.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: Around the world, recovery has become a focus in
      mental health policy. The participation of people accessing mental health
      services (consumers) and carers of such individuals in decision-making related to
      services forms part of this recovery orientation and studies suggest positive
      outcomes following such participation. However, little is known about consumer
      and carer desires at the earliest stages of development of new services. WHAT
      THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Consumers and carers desire changes to
      how mental health services are provided. Many factors affect consumer and carer
      experiences, including language use, physical design of spaces, accessibility,
      consideration of individual needs, practical help and how well care is continued
      from hospital to community settings. Carers may feel sidelined in treatment and
      be distressed as a result. They wish to be respected and involved in recovery.
      Consumers and carers wish for focus on broader health, with care taken to address
      physical health, psychological needs, social needs and treatment of the whole
      person rather than just an illness. WHAT ARE THE IMPLICATIONS FOR PRACTICE?:
      Consumers and carers desire partnership with professionals in recovery.
      Tokenistic participation should be avoided. Flexibility in how services are
      provided and less formality may help engage consumers and carers. Specifically,
      professionals may help by linking consumers and carers to services that address
      practical needs. Professionals should communicate with carers to draw on their
      expertise about the individual accessing the mental health service and help
      carers understand how they can assist the individual's recovery. ABSTRACT:
      Introduction Recovery-oriented mental health policies recognize consumer and
      carer participation in service decision-making as essential, but little is known
      about the views of these individuals in the earliest stages of service
      development. Aim This study sought consumer and carer perspectives addressing the
      establishment of a mental health research, treatment and teaching facility in
      their region. Methods Two 2-hr focus groups were conducted, with separate groups
      held for mental health consumers (n = 9) and carers (n = 9), respectively.
      Discussions pertained to mental health literacy, gaps in current services,
      desires for an ideal facility (in terms of physical design and services offered)
      and what would help in recovery. Results Inductive thematic analysis was used to
      generate three themes: care outside of consultations, carer involvement in
      recovery and holistic approaches to mental health care. Consumers desired a
      facility that could cater to individual needs. Carers felt excluded in recovery
      and unable to provide effective support. Both groups preferred holistic
      approaches to mental health, expressing ambivalence towards medication and
      hospitalization. Discussion Consumers and carers have many needs that
      conventional practices may not meet. Implications for practice They have clear
      desires for equal partnership in recovery and for transformation of conventional
      treatment methods.

PMID- 28449292
TI  - Oral health beliefs, knowledge, and behaviors in Northern California American
      Indian and Alaska Native mothers regarding early childhood caries.
AB  - OBJECTIVES: To assess the oral health beliefs, knowledge, and behaviors related
      to early childhood caries (ECC) risk in a convenience sample of American Indian
      and Alaska Native (AIAN) mothers residing in rural Northern California
      communities. METHODS: Fifty-three mothers of young children were recruited from
      three tribal communities in Northern California with the assistance of the
      California Rural Indian Health Board, Inc. and its California Tribal Epidemiology
      Center and Dental Support Center. Trained study staff administered questionnaires
      to obtain basic socio-demographic information, to survey participants on their
      oral health beliefs, knowledge, and behaviors as related to ECC risk, and to
      identify possible barriers to their accessing professional oral health care.
      Analyses of covariance were used to explore associations between socio
      demographic indicators and oral health behaviors, after controlling for
      knowledge, beliefs and barriers to care. RESULTS: Overall, 53 percent of
      participants reported their oral health as "fair" or "poor." Mothers' education
      (high) and being employed were positively associated with better oral health
      behavior scores. Additionally, 72 percent of mothers reported having one or more
      barriers to oral health care including access. There was a significant relation
      (P = 0.03) between high number of reported barriers to oral health care and low
      oral health behavior scores. CONCLUSIONS: Despite generally high-level oral
      health knowledge, perceptions of self and child oral health remains low in this
      sample of AIAN mothers. Factors identified as being associated with oral health
      behaviors in this sample were similar to those found in other health disparities
      populations.

PMID- 28449293
TI  - A Novel Approach to Study Medical Decision Making in the Clinical Setting: The
      "Own-point-of-view" Perspective.
AB  - BACKGROUND: Making diagnostic and therapeutic decisions is a critical activity
      among physicians. It relies on the ability of physicians to use cognitive
      processes and specific knowledge in the context of a clinical reasoning. This
      ability is a core competency in physicians, especially in the field of emergency
      medicine where the rate of diagnostic errors is high. Studies that explore
      medical decision making in an authentic setting are increasing significantly.
      They are based on the use of qualitative methods that are applied at two separate
      times: 1) a video recording of the subject's actual activity in an authentic
      setting and 2) an interview with the subject, supported by the video recording.
      Traditionally, activity is recorded from an "external perspective"; i.e., a
      camera is positioned in the room in which the consultation takes place. This
      approach has many limits, both technical and with respect to the validity of the
      data collected. OBJECTIVES: The article aims at 1) describing how decision making
      is currently being studied, especially from a qualitative standpoint, and the
      reasons why new methods are needed, and 2) reporting how we used an original,
      innovative approach to study decision making in the field of emergency medicine
      and findings from these studies to guide further the use of this method. The
      method consists in recording the subject's activity from his own point of view,
      by fixing a microcamera on his temple or the branch of his glasses. An interview
      is then held on the basis of this recording, so that the subject being
      interviewed can relive the situation, to facilitate the explanation of his
      reasoning with respect to his decisions and actions. RESULTS: We describe how
      this method has been used successfully in investigating medical decision making
      in emergency medicine. We provide details on how to use it optimally, taking into
      account the constraints associated with the practice of emergency medicine and
      the benefits in the study of clinical reasoning. CONCLUSION: The "own-point-of
      view" video technique is a promising method to study clinical decision making in
      emergency medicine. It is a powerful tool to stimulate recall and help physicians
      make their reasoning explicit, thanks to a greater psychological immersion.

PMID- 28449294
TI  - Analysis of the prognostic value of BMI and the difference in its impact
      according to age and sex in DLBCL patients.
AB  - Studies that have evaluated the prognostic value of body mass index (BMI) in
      patients with diffuse large B-cell lymphoma have recently been reported. However,
      the impact of BMI on survival outcomes remains controversial. We retrospectively
      analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R
      CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized
      into 1 of 4 groups according to BMI were underweight (<18.5 kg/m2 ), 58 (14.3%);
      normal weight (>=18.5 to <25 kg/m2 ), 262 (64.5%); overweight (>=25 to <30 kg/m2
      ), 75 (18.5%); and obese (>=30.0 kg/m2 ), 11 (2.7%). While the prognosis of
      overweight patients was good, being similar to that of normal weight,
      underweight, and obese patients had a worse prognosis (5-y overall survival [OS]
      was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight,
      and obese patients, respectively; P = .004). In multivariate analysis,
      underweight and obesity were independent prognostic factors for OS compared with
      normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female
      patients (>=70 y), patients with a low BMI (<25 kg/m2 ) had significantly
      inferior OS than those with a high BMI (>=25 kg/m2 ) (5-y OS, 61.5% vs 85.7%; P =
      .039). In contrast, in young female patients (<70 years), patients with a low BMI
      had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P
      < .001). In male patients, there were no differences in the effect of BMI on OS
      between young and elderly patients. In this study, we demonstrated that being
      underweight and obese were independent prognostic factors compared with being
      normal weight. In female patients, BMI had a different impact on the prognosis of
      young and elderly patients, whereas in male patients, there was no difference in
      the effect of BMI on prognosis according to age.

PMID- 28449295
TI  - KBG syndrome: An Australian experience.
AB  - In 2011, heterozygous mutations in the ANKRD11 gene were identified in patients
      with KBG syndrome. Since then, 100 cases have been described with the expansion
      of the clinical phenotype. Here we present 18 KBG affected individuals from 13
      unrelated families, 16 with pathogenic mutations in the ANKRD11 gene. Consistent
      features included intellectual disability, macrodontia, and the characteristic
      broad forehead with hypertelorism, and a prominent nasal bridge. Common features
      included hand anomalies, cryptorchidism, and a large number of palate
      abnormalities. Distinctive findings in this series included malrotation of the
      abdominal viscera, bilateral inguinal herniae in two patients, basal ganglia
      calcification and the finding of osteopenia in three patients. Nine novel
      heterozygous variants were found and the genotype-phenotype correlation was
      explored. This report highlights the need for thorough examination and
      investigation of the dental and skeletal systems. The results confirm the
      specificity of ANKRD11 mutations in KBG and further evidence for this
      transcription repressor in neural, cardiac, and skeletal development. The
      description of further cases of KBG syndrome is needed to further delineate this
      condition, in particular the specific neurological and behavioral phenotype.

PMID- 28449296
TI  - Frailty index: Intensive care unit complications in head and neck oncologic
      regional and free flap reconstruction.
AB  - BACKGROUND: Head and neck extirpations requiring reconstruction are challenging
      surgeries with high postoperative complication risk. METHODS: Regional and free
      flap reconstructions of head and neck defects were collected from the 2006-2013
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP) database. The modified frailty index was made of 15 variables, with
      increasing index scores indicative of frailer patients. Intensive care unit (ICU)
      level complications were defined by Clavien-Dindo classification IV and analyzed
      with multivariable logistic regression. RESULTS: There were 266 flap
      reconstructions (126 regional and 140 free) with 86 (7.2%) Clavien-Dindo
      classification IV complications. As modified frailty index increased, a moderate
      correlation was demonstrated for Clavien-Dindo classification IV complications
      (R2 = 0.30). Increasing modified frailty index score was correlated on linear
      regression with free versus regional flaps: Clavien-Dindo classification IV (R2 =
      0.09; 0.60), morbidity (R2 = 0.04; 0.59), and mortality (R2 = 0.07; 0.46),
      respectively. On multivariable analysis, the modified frailty index was
      associated with Clavien-Dindo classification IV complications for all flaps (odds
      ratio [OR] 4.38; 95% confidence interval [CI] 1.33-14.48) and free flaps (OR
      6.60; 95%CI 1.02-42.52), but not regional flaps (OR 9.05; 95%CI 0.60-137.10).
      CONCLUSION: The modified frailty index score is predictive of critical care
      support in head and neck resections necessitating reconstruction, specifically
      for free flaps.

PMID- 28449297
TI  - Physics, History, and the German Atomic Bomb.
AB  - Physics, History, and the German Atomic Bomb. This paper examines the German
      concept of a nuclear weapon during National Socialism and the Second World War.
      Zusammenfassung: Physik, Geschichte und die deutsche Atombombe. Dieser Aufsatz
      untersucht die deutsche Vorstellung einer nuklearen Waffe wahrend des
      Nationalsozialismus und des Zweiten Weltkrieges.

PMID- 28449298
TI  - All-Silicon Switchable Magnetoelectric Effect through Interlayer Exchange
      Coupling.
AB  - The magnetoelectric (ME) effect originating from the effective coupling between
      electric field and magnetism is an exciting frontier in nanoscale science such as
      magnetic tunneling junction (MTJ), ferroelectric/piezoelectric heterojunctions
      etc. The realization of switchable ME effect under external electric field in d0
      semiconducting materials of single composition is needed especially for all
      silicon spintronics applications because of its natural compatibility with
      current industry. We employ density functional theory (DFT) to reveal that the
      pristine Si(111)-3*3 R30 degrees  (Si3 hereafter) reconstructed surfaces of thin
      films with a thickness smaller than eleven bilayers support a sizeable linear ME
      effect with switchable direction of magnetic moment under external electric
      field. This is achieved through the interlayer exchange coupling effect in the
      antiferromagnetic regime, where the spin-up and spin-down magnetized density is
      located on opposite surfaces of Si3 thin films. The obtained coefficient for the
      linear ME effect can be four times larger than that of ferromagnetic Fe films,
      which fail to have the reversal switching capabilities. The larger ME effect
      originates from the spin-dependent screening of the spin-polarized Dirac fermion.
      The prediction will promote the realization of well-controlled and switchable
      data storage in all-silicon electronics.

PMID- 28449299
TI  - Arnold Bernard Scheibel, M.D. (1923-2017).

PMID- 28449300
TI  - The effect of canaloplasty with suprachoroidal drainage combined with cataract
      surgery - 1-year results.
AB  - PURPOSE: The purpose of this study was to investigate the safety and efficacy of
      phacocanaloplasty with suprachoroidal drainage (PCscD) and to compare its
      intraocular pressure (IOP)-lowering and drug-sparing effect to canaloplasty with
      suprachoroidal drainage (CscD). METHODS: The study retrospective interventional
      study included patients with open-angle glaucoma or secondary forms of glaucoma
      who underwent either CscD or PCscD between the year 2011 and 2014 in Knappschaft
      Eye Clinic Sulzbach. Primary end-points were IOP reduction and the number of IOP
      lowering medication after 12 months. Secondary end-points were intraoperative and
      postoperative complications. RESULTS: A total of 328 eyes were included, 193 were
      treated with CscD and 135 underwent PCscD. Canaloplasty with scD achieved an IOP
      reduction of 37.0% (from 20.9 +/- 3.6 mmHg to 13.2 +/- 2.6 mmHg) after 1 year,
      whereas PCscD showed a significant higher reduction of 47.4% (from 23.2 +/- 5.1
      mmHg to 12.2 +/- 1.7 mmHg). Reduction in IOP-lowering medication was higher after
      PCscD (from 3.6 +/- 0.6 to 0.2 +/- 0.5) than after CscD (from 3.5 +/- 0.8 to 0.7
      +/- 1.0). Twelve months after surgery 55.5% in the CscD group and 80.2% in the
      PCscD group were free of IOP-lowering medication. In both groups, no severe or
      sight-threatening complications occurred. CONCLUSION: Combining cataract surgery
      and CscD achieves a higher IOP reduction, and patients postoperatively need less
      IOP-lowering medication than after CscD alone.

PMID- 28449301
TI  - The Profile and Dynamics of RNA Modifications in Animals.
AB  - More than a hundred distinct modified nucleosides have been identified in RNA,
      but little is known about their distribution across different organisms, their
      dynamic nature and their response to cellular and environmental stress. Mass
      spectrometry-based methods have been at the forefront of identifying and
      quantifying modified nucleosides. However, they often require synthetic reference
      standards, which do not exist in the case of many modified nucleosides, and this
      therefore impedes their analysis. Here we use a metabolic labelling approach to
      achieve rapid generation of bio-isotopologues of the complete Caenorhabditis
      elegans transcriptome and its modifications and use them as reference standards
      to characterise the RNA modification profile in this multicellular organism
      through an untargeted liquid-chromatography tandem high-resolution mass
      spectrometry (LC-HRMS) approach. We furthermore show that several of these RNA
      modifications have a dynamic response to environmental stress and that, in
      particular, changes in the tRNA wobble base modification 5-methoxycarbonylmethyl
      2-thiouridine (mcm5 s2 U) lead to codon-biased gene-expression changes in starved
      animals.

PMID- 28449302
TI  - Prescribing Safety Assessment 2016: Delivery of a national prescribing assessment
      to 7343 UK final-year medical students.
AB  - AIMS: Newly graduated doctors write a large proportion of prescriptions in UK
      hospitals but recent studies have shown that they frequently make prescribing
      errors. The prescribing safety assessment (PSA) has been developed as an
      assessment of competence in relation to prescribing and supervising the use of
      medicines. This report describes the delivery of the PSA to all UK final-year
      medical students in 2016 (PSA2016). METHODS: The PSA is a 2-hour online
      assessment comprising eight sections which cover various aspects of prescribing
      defined within the outcomes of undergraduate education identified by the UK
      General Medical Council. Students sat one of four PSA 'papers', which had been
      standard-set using a modified Angoff process. RESULTS: A total of 7343 final-year
      medical students in all 31 UK medical schools sat the PSA. The overall pass rate
      was 95% with the pass rates for the individual papers ranging from 93 to 97%. The
      PSA was re-sat by 261 students who had failed and 80% of those candidates passed.
      The internal consistency (Cronbach's alpha) of the four papers ranged from 0.74
      to 0.77 (standard error of measurement 4.13-4.24%). There was a statistically
      significant variation in performance between medical school cohorts (F = 32.6, P
      < 0.001) and a strongly positive correlation in performance for individual
      schools between PSA2015 and PSA2016 (r = 0.79, 95% CI 0.61-0.90; P < 0.01).
      CONCLUSIONS: PSA2016 demonstrated the feasibility of delivering a standardized
      national prescribing assessment online. The vast majority of UK final-year
      medical students were able to meet a prespecified standard of prescribing
      competence.

PMID- 28449303
TI  - Brief intervention, physical exercise and cognitive behavioural group therapy for
      patients with chronic low back pain (The CINS trial).
AB  - BACKGROUND AND OBJECTIVE: Cognitive-behavioural treatments (CBT) and physical
      group exercise (PE) have both shown promising effects in reducing disability and
      increasing work participation among chronic low back pain (CLBP) patients. A
      brief cognitive intervention (BI) has previously been demonstrated to reduce work
      disability in CLBP. The aim of this study was to test if the effect of BI could
      be further increased by adding either group CBT or group PE. METHODS: A total of
      214 patients, all sick listed 2-10 months due to CLBP, were randomized to BI (n =
      99), BI + group CBT (n = 55) or BI + group PE (n = 60). Primary outcome was
      increased work participation at 12 months, whereas secondary outcomes included
      pain-related disability, subjective health complaints, anxiety, depression,
      coping and fear avoidance. RESULTS: There were no significant differences between
      the groups in work participation at 12 months follow-up (chi2  = 1.15, p = 0.56).
      No significant differences were found on the secondary outcomes either, except
      for a statistically significant reduction (time by group) in pseudoneurology one
      domain of subjective health complaints (sleep problems, tiredness, dizziness,
      anxiety, depression, palpitation, heat flushes) (F2,136  = 3.109, p = 0.048) and
      anxiety (F2,143  = 4.899, p = 0.009) for the groups BI + group CBT and BI + group
      PE, compared to BI alone. However, these differences were not significant in post
      hoc analyses (Scheffe adjusted). CONCLUSION: There was no support for an effect
      of the added group CBT or group PE treatments to a brief cognitive intervention
      in this study of patients on sick leave due to low back pain. SIGNIFICANCE: Our
      study demonstrates that treatments that previously were found to be effective and
      are included in most treatment guidelines, such as group cognitive-behavior
      therapy and exercise, were not effective in this given context compared to a
      brief, cognitive intervention. This implies that an optimized brief intervention
      is difficult to outperform in patients on sick leave due to low back pain.

PMID- 28449304
TI  - A case of familial transmission of the newly described DNMT3A-Overgrowth
      Syndrome.
AB  - DNMT3A-Overgrowth Syndrome (also known as Tatton-Brown-Rahman Syndrome) (MIM
      615879) has recently been described in 13 individuals with de novo heterozygous
      mutations in DNMT3A gene. This autosomal dominant condition is characterized by
      overgrowth, dysmorphic facial features and moderate intellectual disability.
      Missense and truncating point mutations, a small in-frame deletion, as well as
      microdeletion 2p23 have been reported. Moreover, DNMT3A is commonly somatically
      mutated in acute myeloid leukemia. We herein report a family with two siblings
      and their father affected by the syndrome. The proband is a 12 year-old boy with
      tall stature, macrocephaly, facial dysmorphism, and intellectual disability. His
      10-year-old sister also has learning difficulties, overgrowth and mild facial
      dysmorphism. Their father is a 49 year-old man with tall stature, macrocephaly,
      learning difficulties, and minor facial dysmorphism. He had a right occipital
      osteoma removed at 20 years of age. A heterozygous splice site mutation
      NM_022552.4 (DNMT3A): c.2323-2A > T was found in the proband by whole exome
      sequencing analysis and by targeted Sanger Sequencing for the proband's sister
      and father. This mutation has not been previously reported and is believed to be
      pathogenic. Indeed, this substitution involves a highly conserved canonical
      splice site and is predicted to cause exon skipping. This is the first report of
      a familial transmission of DNMT3A-Overgrowth Syndrome, supporting the autosomal
      dominant inheritance. The proband's phenotype is more severe than that of his two
      other affected family members, which illustrates variable expressivity in the
      syndrome.

PMID- 28449305
TI  - C-reactive protein variability is associated with vascular access outcome in
      hemodialysis patients.
AB  - BACKGROUND: Hemodialysis (HD) vascular access failure is one of the most
      important causes of morbidity and contributes to the cost of dialysis care. There
      is paucity of data evaluating long-term monitoring of C-reactive protein (CRP) on
      outcome of HD vascular access. METHODS: We conducted a retrospective study to
      investigate whether variability of serum CRP level was associated with vascular
      access failure rate over a 7-year period. A total of 318 HD patients were
      included. Their demographic data, co-morbidities and biochemical data were
      reviewed and collected. Serum high-sensitivity CRP (hs-CRP) level was measured
      every 6 months. Patients were divided into three groups according to their serial
      hs-CRP levels. Patients with their hs-CRP below 2 mg/L were defined as low group
      (n=65, 20.4%) and those with higher than 4 mg/L were defined as high (n=39,
      12.3%). The rest were classified as fluctuated hs-CRP group (n=214, 67.3%).
      Treatment of vascular access failure includes angioplasty and access re-creation.
      RESULTS: Their body mass index, indicators of dialysis adequacy and serum albumin
      and hs-CRP levels differed significantly among three groups. The annual vascular
      access failure rate was significantly higher in fluctuated hs-CRP group than in
      high hs-CRP group (0.41 vs 0.36, P=.037). Serum albumin was a significant
      associate of vascular access failure. Kaplan-Meier survival analysis indicated
      patients with high or fluctuated hs-CRP had shorter free interval of vascular
      access failure than low hs-CRP group. CONCLUSIONS: HD patients with fluctuated hs
      CRP levels were associated with increased vascular access failure.

PMID- 28449306
TI  - Malignant ovarian germ cell tumors in pediatric patients: The AIEOP (Associazione
      Italiana Ematologia Oncologia Pediatrica) study.
AB  - OBJECTIVE: Malignant ovarian germ cell tumors (MOGCT) carry an excellent
      prognosis, and the treatment aims to achieve results with the least possible
      treatment-related morbidity. The aim of this study was to assess the outcomes of
      pediatric patients with MOGCT. METHODS: Patients were treated according to their
      stage: surgery and surveillance for stage I; a modified bleomycin-etoposide
      cisplatin (BEP) regimen for stages II (three cycles), III, and IV (three cycles)
      with surgery on residual disease. RESULTS: Seventy-seven patients were enrolled
      (median age 11.8 years), 26 with dysgerminoma (Dysg), 13 with immature teratoma
      and elevated serum alpha-fetoprotein levels (IT + AFP), and 38 with
      nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage
      III, 5 stage IV. Among evaluable patients in stage I (5-year event-free survival
      [EFS] 72.1% [95% CI: 56.4-92.1%]; 5-year overall survival [OS] 100%), seven
      relapsed (three patients with Dysg and four patients with Non-Dysg) and were
      rescued with chemotherapy (plus surgery in three patients). Among the evaluable
      patients with stages II-IV, 48 (98%) achieved complete remission after
      chemotherapy +/- surgery, one (IT + AFP, stage IV) had progressive disease. In
      the whole series (median follow-up 80 months), the 5-year OS and EFS were 98.5%
      (95% CI: 95.6-100%) and 84.5% (95% CI: 76.5-93.5%). CONCLUSIONS: We confirm the
      excellent outcome for MOGCT. Robust data are lacking on surgical staging,
      surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most
      appropriate BEP regimen. As pediatric oncologists, we support the role of
      surveillance after proper surgical staging providing cases are managed by experts
      at specialized pediatric centers.

PMID- 28449307
TI  - The efficacy of non-narcotic analgesics on post-operative endodontic pain: A
      systematic review and meta-analysis: The efficacy of non-steroidal anti
      inflammatory drugs and/or paracetamol on post-operative endodontic pain.
AB  - The objective of this review was to evaluate the efficacy of non-narcotic
      analgesics including non-steroidal anti-inflammatory drugs (NSAIDs) and/or
      paracetamol in the treatment of post-operative endodontic pain. Additionally, we
      aimed to examine the possible association of study covariates on the pain scores
      using meta-regression analysis. An electronic search was performed in 2016. After
      data extraction and quality assessment of the included studies (n = 27,
      representing 2188 patients), meta-analysis was performed using a random-effect
      inverse variance method. Meta-regression analysis was conducted to examine the
      associations between effect sizes and study-level covariates (P < 0.05). The
      results showed that administration of non-narcotic analgesic was more effective
      than placebo in the management of post-operative pain, resulting in a lower pain
      scores with a standardised mean difference of -0.50 (95% CI= -0.70, -0.30), -0.76
      (95%CI= -0.95, -0.56), -1.15 (95% CI= -1.52, -0.78), -0.65 (95% CI= -1.05, -0.26)
      for immediately after the procedure, 6-, 12- and 24 h post-operative follow-ups
      (test for statistical heterogeneity: P = 0.000, P = 0.000, P = 0.000 and P =
      0.001), respectively. Our meta-regression analysis provided the evidence for
      association between some study covariates with treatment effect, each at
      different follow-ups. We concluded that the clinicians can manage post-operative
      endodontic pain by administration of NSAIDs and/or paracetamol. However,
      analgesic regimens should be considered as important determinants when
      prescribing a pharmacological adjuvant.

PMID- 28449308
TI  - A qualitative study of the knowledge, behaviour and attitudes of patients with
      skin cancer regarding sunlight exposure and vitamin D.
AB  - BACKGROUND: Solar UVR is a major cause of skin cancer but also an important
      source of vitamin D (VitD), essential for musculoskeletal health. Conflicting
      public health messages may confuse patients with skin cancer prone to further
      skin cancer. OBJECTIVE: To explore the knowledge, behaviour and attitudes of
      patients with skin cancer to sunlight exposure and VitD sources. METHODS:
      Patients (n = 10) previously treated for multiple basal cell cancer in a hospital
      setting participated in focus group sessions with semi-structured discussions to
      explore: knowledge of VitD, sun-avoidance behaviour and attitude towards sunlight
      exposure messages. Thematic data analysis was performed using software programme
      MAXQDA11. RESULTS: Pre-existing knowledge of VitD was low. Most patients
      practised sun avoidance and were not inclined to increase exposure. Patients did
      not perceive VitD deficiency as a substantial risk to their own health, or a need
      to take VitD supplements. They aimed to increase VitD status through dietary
      intake, but knowledge of food VitD content was lacking. CONCLUSIONS: The patients
      with skin cancer, appropriate to their heightened skin cancer risk, appeared
      unlikely to increase their sun exposure to gain VitD. However, education is
      required regarding the generally low levels of VitD in foodstuffs, and the
      requirement for supplements/fortified foods if strict sun avoidance is employed.

PMID- 28449309
TI  - Tumor Targeting with an isoDGR-Drug Conjugate.
AB  - Herein we report the first example of an isoDGR-drug conjugate (2), designed to
      release paclitaxel selectively within cancer cells expressing integrin alphaV
      beta3 . Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5
      with paclitaxel via the lysosomally cleavable Val-Ala dipeptide linker. Conjugate
      2 displayed a low nanomolar affinity for the purified integrin alphaV beta3
      receptor (IC50 =11.0 nm). The tumor targeting ability of conjugate 2 was assessed
      in vitro in anti-proliferative assays on two isogenic cancer cell lines
      characterized by different integrin alphaV beta3 expression: human glioblastoma
      U87 (alphaV beta3 +) and U87 beta3 -KO (alphaV beta3 -). The isoDGR-PTX conjugate
      2 displayed a remarkable targeting index (TI=9.9), especially when compared to
      the strictly related RGD-PTX conjugate 4 (TI=2.4).

PMID- 28449310
TI  - Rational Design of Nanobody80 Loop Peptidomimetics: Towards Biased beta2
      Adrenergic Receptor Ligands.
AB  - G protein-coupled receptors (GPCRs) play an important role in many cellular
      responses; as such, their mechanism of action is of utmost interest. To gain
      insight into the active conformation of GPCRs, the X-ray crystal structures of
      nanobody (Nb)-stabilized beta2 -adrenergic receptor (beta2 AR) have been
      reported. Nb80, in particular, is able to bind the intracellular G protein
      binding site of beta2 AR and stabilize the receptor in an active conformation.
      Within Nb80, the complementarity-determining region 3 (CDR3) is responsible for
      most of the binding interactions. Hence, we hypothesized that peptidomimetics of
      the CDR3 loop might be sufficient for binding to the receptor, inhibiting the
      interaction of beta2 AR with intracellular GPCR interacting proteins (e.g., G
      proteins). Based on previous crystallographic data, a set of peptidomimetics were
      synthesized that, similar to the Nb80 CDR3 loop, adopt a beta-hairpin
      conformation. Syntheses, conformational analysis, binding and functional in vitro
      assays, as well as internalization experiments, were performed. We demonstrate
      that peptidomimetics can structurally mimic the CDR3 loop of a nanobody and its
      function by inhibiting G protein coupling as measured by partial inhibition of
      cAMP production.

PMID- 28449311
TI  - Reproducibility of the International Endometrial Analysis Group Color Score for
      Assigning the Amount of Flow Within the Endometrium Using Stored 3-Dimensional
      Volumes.
AB  - OBJECTIVES: To estimate intraobserver and interobserver reproducibility for
      assigning an International Endometrial Tumor Analysis (IETA) group color score
      for endometrial vascularization on color Doppler imaging. METHODS: Sixty-eight
      endometrial 3-dimensional volumes from endometrial color Doppler assessments of
      women with different endometrial disorders were evaluated by 8 different
      examiners (4 skilled examiners and 4 obstetric and gynecologic trainees). One
      skilled examiner who did not participate in the assessments selected the 68
      volumes from a database to select a balanced number of each IETA score. Each
      examiner evaluated the 68 endometrial volumes to assign the IETA color score (1,
      absence of vascularization; 2, low vascularization; 3, moderate vascularization;
      or 4, abundant vascularization) using tomographic ultrasound imaging. The
      analysis was repeated 4 weeks later, and interobserver and intraobserver
      reproducibility was analyzed by calculating the weighted kappa index. The second
      of the measurements made by each observer was used to estimate interobserver
      reproducibility. RESULTS: The intraobserver reproducibility was very good for all
      examiners, with a weighted kappa index ranging from 0.84 to 0.91. The
      interobserver reproducibility was good or very good for all estimated
      comparisons, with a weighted kappa index ranging from 0.77 to 0.96, regardless of
      experience level. CONCLUSIONS: The reproducibility of assigning the IETA color
      score for assessing endometrial vascularization using 3-dimensional volumes is
      good or very good regardless of the experience of the examiner.

PMID- 28449312
TI  - The effect of sclerotherapy and prolotherapy on chronic painful Achilles
      tendinopathy-a systematic review including meta-analysis.
AB  - Chronic painful Achilles tendinopathy (AT) is a common disorder among athletes.
      Sclerotherapy (ST) and prolotherapy (PT) are two promising options among the
      numerous other conservative therapies. As their efficacy and potential adverse
      effects (AE) are still unclear, we systematically searched, analyzed, and
      synthesized the available literature on ST and PT for treating AT. Electronic
      databases, Google Scholar and articles' reference lists were searched according
      to PRISMA guidelines. Eligibility criteria were set up according to the PICOS
      scheme including human and animal studies. Three authors independently reviewed
      the results and evaluated methodological quality (Coleman Methodology Score and
      Cochrane Risk of Bias Assessment). The initial search yielded 1104 entries. After
      screening, 18 articles were available for qualitative synthesis, six of which
      were subjected to meta-analysis. The mean Coleman Score of the 13 human studies
      was 50. Four RCTs were ranked as having a low risk of selection bias. Three of
      those reported a statistically significant drop in the visual analog scale (VAS)
      score, one a significant increase in the VISA-A Score. 12 of 13 human studies
      reported positive results in achieving pain relief and patient satisfaction,
      whereas only one study's finding differed. Meta-analysis revealed an unambiguous
      result in favor of the intervention (weighted mean difference D=-4.67 cm, 95% CI 
      5.56 to -3.76 cm [P<.001]). Only one serious AE and two minor AEs were reported
      in the entire literature. This systematic review suggests that ST and PT may be
      effective treatment options for AT and that they can be considered safe. Long
      term studies and RCTs are still needed to support their recommendation.

PMID- 28449313
TI  - Neurovascular unit alteration in somatosensory cortex and enhancement of thermal
      nociception induced by amphetamine involves central AT1 receptor activation.
AB  - The use of psychostimulants, such as amphetamine (Amph), is associated with
      inflammatory processes, involving glia and vasculature alterations. Brain
      Angiotensin II (Ang II), through AT1 -receptors (AT1 -R), modulates
      neurotransmission and plays a crucial role in inflammatory responses in brain
      vasculature and glia. Our aim for the present work was to evaluate the role of
      AT1 -R in long-term alterations induced by repeated exposure to Amph. Astrocyte
      reactivity, neuronal survival and brain microvascular network were analysed at
      the somatosensory cortex. Thermal nociception was evaluated as a physiological
      outcome of this brain area. Male Wistar rats (250-320 g) were administered with
      AT1 -R antagonist Candesartan/vehicle (3 mg/kg p.o., days 1-5) and Amph/saline
      (2.5 mg/kg i.p., days 6-10). The four experimental groups were: Veh-Sal, CV-Sal,
      Veh-Amph, CV-Amph. On day 17, the animals were sacrificed and their brains were
      processed for Nissl staining and immunohistochemistry against glial fibrillary
      acidic protein (GFAP) and von Willebrand factor. In another group of animals,
      thermal nociception was evaluated using hot plate test, in the four experimental
      groups, on day 17. Data were analysed with two-way anova followed by Bonferroni
      test. Our results indicate that Amph exposure induces an increase in: neuronal
      apoptosis, astrocyte reactivity and microvascular network, evaluated as an
      augmented occupied area by vessels, branching points and their tortuosity.
      Moreover, Amph exposure decreased the thermal nociception threshold. Pretreatment
      with the AT1 -R blocker prevented the described alterations induced by this
      psychostimulant. The decreased thermal nociception and the structural changes in
      somatosensory cortex could be considered as extended neuroadaptative responses to
      Amph, involving AT1 -R activation.

PMID- 28449314
TI  - Characterization of the anti-CD22 targeted therapy, moxetumomab pasudotox, for B
      cell precursor acute lymphoblastic leukemia.
AB  - Moxetumomab pasudotox is a second-generation recombinant immunotoxin against CD22
      on B-cell lineages. Antileukemic activity has been demonstrated in children with
      chemotherapy-refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL),
      with variable responses. Here, we report in vitro and in vivo evaluation of
      moxetumomab pasudotox treatment of human cell lines and patient-derived cells as
      a preliminary study to understand characteristics of sensitivity to treatment.
      Binding, internalization, and apoptosis were evaluated using fluorescently tagged
      moxetumomab pasudotox. Studies in NOD-scid IL2Rgnull mice showed a modest
      survival benefit in mice engrafted with 697 cells but not in NALM6 or the two
      patient-derived xenograft models.

PMID- 28449315
TI  - panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical
      diagnostics.
AB  - Targeted next-generation-sequencing (NGS) panels have largely replaced Sanger
      sequencing in clinical diagnostics. They allow for the detection of copy-number
      variations (CNVs) in addition to single-nucleotide variants and small
      insertions/deletions. However, existing computational CNV detection methods have
      shortcomings regarding accuracy, quality control (QC), incidental findings, and
      user-friendliness. We developed panelcn.MOPS, a novel pipeline for detecting CNVs
      in targeted NGS panel data. Using data from 180 samples, we compared panelcn.MOPS
      with five state-of-the-art methods. With panelcn.MOPS leading the field, most
      methods achieved comparably high accuracy. panelcn.MOPS reliably detected CNVs
      ranging in size from part of a region of interest (ROI), to whole genes, which
      may comprise all ROIs investigated in a given sample. The latter is enabled by
      analyzing reads from all ROIs of the panel, but presenting results exclusively
      for user-selected genes, thus avoiding incidental findings. Additionally,
      panelcn.MOPS offers QC criteria not only for samples, but also for individual
      ROIs within a sample, which increases the confidence in called CNVs. panelcn.MOPS
      is freely available both as R package and standalone software with graphical user
      interface that is easy to use for clinical geneticists without any programming
      experience. panelcn.MOPS combines high sensitivity and specificity with user
      friendliness rendering it highly suitable for routine clinical diagnostics.

PMID- 28449316
TI  - Does my high blood pressure improve your survival? Overall and subgroup learning
      curves in health.
AB  - Learning curves in health are of interest for a wide range of medical
      disciplines, healthcare providers, and policy makers. In this paper, we
      distinguish between three types of learning when identifying overall learning
      curves: economies of scale, learning from cumulative experience, and human
      capital depreciation. In addition, we approach the question of how treating more
      patients with specific characteristics predicts provider performance. To soften
      collinearity problems, we explore the use of least absolute shrinkage and
      selection operator regression as a variable selection method and Theil-Goldberger
      mixed estimation to augment the available information. We use data from the
      Belgian Transcatheter Aorta Valve Implantation (TAVI) registry, containing
      information on the first 860 TAVI procedures in Belgium. We find that treating an
      additional TAVI patient is associated with an increase in the probability of 2
      year survival by about 0.16%-points. For adverse events like renal failure and
      stroke, we find that an extra day between procedures is associated with an
      increase in the probability for these events by 0.12%-points and 0.07%-points,
      respectively. Furthermore, we find evidence for positive learning effects from
      physicians' experience with defibrillation, treating patients with hypertension,
      and the use of certain types of replacement valves during the TAVI procedure.

PMID- 28449317
TI  - A comparison of individual-based genetic distance metrics for landscape genetics.
AB  - A major aim of landscape genetics is to understand how landscapes resist gene
      flow and thereby influence population genetic structure. An empirical
      understanding of this process provides a wealth of information that can be used
      to guide conservation and management of species in fragmented landscapes and also
      to predict how landscape change may affect population viability. Statistical
      approaches to infer the true model among competing alternatives are based on the
      strength of the relationship between pairwise genetic distances and landscape
      distances among sampled individuals in a population. A variety of methods have
      been devised to quantify individual genetic distances, but no study has yet
      compared their relative performance when used for model selection in landscape
      genetics. In this study, we used population genetic simulations to assess the
      accuracy of 16 individual-based genetic distance metrics under varying sample
      sizes and degree of population genetic structure. We found most metrics performed
      well when sample size and genetic structure was high. However, it was much more
      challenging to infer the true model when sample size and genetic structure was
      low. Under these conditions, we found genetic distance metrics based on principal
      components analysis were the most accurate (although several other metrics
      performed similarly), but only when they were derived from multiple principal
      components axes (the optimal number varied depending on the degree of population
      genetic structure). Our results provide guidance for which genetic distance
      metrics maximize model selection accuracy and thereby better inform conservation
      and management decisions based upon landscape genetic analysis.

PMID- 28449318
TI  - Screening, diagnosis and management of human cysticercosis and Taenia solium
      taeniasis: technical recommendations by the COHEMI project study group.
AB  - Neurocysticercosis, the central nervous system's localised form of cysticercosis,
      is considered to be the leading cause of epilepsy in the developing world. In
      Europe, the disease is mainly imported and affects both immigrants and
      travellers. However, autochthonous cases of cysticercosis in low-endemic
      countries could also originate from Taenia solium carriers (migrants or
      travellers) who acquired taeniasis overseas. Management of cysticercosis is a
      challenge for European healthcare providers as they are often hardly aware of
      this infection and have little familiarity in managing this disease. This study
      provides a summary of recommendations concerning screening, diagnosis and
      management of cysticercosis and T. solium taeniasis in Europe drawn up by nine
      experts in migrant health and imported diseases with experience in cysticercosis
      and T. solium taeniasis.

PMID- 28449319
TI  - Comparison of administrative and survey data for estimating vitamin A
      supplementation and deworming coverage of children under five years of age in Sub
      Saharan Africa.
AB  - OBJECTIVE: To compare administrative coverage data with results from household
      coverage surveys for vitamin A supplementation (VAS) and deworming campaigns
      conducted during 2010-2015 in 12 African countries. METHODS: Paired t-tests
      examined differences between administrative and survey coverage for 52 VAS and 34
      deworming dyads. Independent t-tests measured VAS and deworming coverage
      differences between data sources for door-to-door and fixed-site delivery
      strategies and VAS coverage differences between 6- to 11-month and 12- to 59
      month age group. RESULTS: For VAS, administrative coverage was higher than survey
      estimates in 47 of 52 (90%) campaign rounds, with a mean difference of 16.1% (95%
      CI: 9.5-22.7; P < 0.001). For deworming, administrative coverage exceeded survey
      estimates in 31 of 34 (91%) comparisons, with a mean difference of 29.8% (95% CI:
      16.9-42.6; P < 0.001). Mean +/- SD differences in coverage between administrative
      and survey data were 12.2% +/- 22.5% for the door-to-door delivery strategy and
      25.9% +/- 24.7% for the fixed-site model (P = 0.06). For deworming, mean +/- SD
      differences in coverage between data sources were 28.1% +/- 43.5% and 33.1% +/-
      17.9% for door-to-door and fixed-site distribution, respectively (P = 0.64). VAS
      administrative coverage was higher than survey estimates in 37 of 49 (76%)
      comparisons for the 6- to 11-month age group and 45 of 48 (94%) comparisons for
      the 12- to 59-month age group. CONCLUSION: Reliance on health facility data alone
      for calculating VAS and deworming coverage may mask low coverage and prevent
      measures to improve programmes. Countries should periodically validate
      administrative coverage estimates with population-based methods.

PMID- 28449321
TI  - A review of associated controversies surrounding glucocorticoid use in veterinary
      emergency and critical care.
AB  - OBJECTIVE: To review the literature in human and veterinary medicine regarding
      the indications for, efficacy of, and controversies surrounding glucocorticoid
      (GC) administration in the emergency and critical care (ECC) setting, and to
      provide an overview of the most commonly used synthetic GC formulations.
      MEDICATIONS: Synthetic GCs vary in GC and mineralocorticoid potency, hypothalamic
      pituitary axis suppression, duration of action, route of administration, and
      clinical indication for use. Some of the GC compounds commonly used in human and
      veterinary ECC include hydrocortisone, prednisone, methylprednisolone, and
      dexamethasone. INDICATIONS FOR USE: GCs are used in human and veterinary ECC for
      a variety of disorders including anaphylaxis, acute lung injury/acute respiratory
      distress syndrome, septic shock, and spinal cord injury. Evidence for morbidity
      or mortality benefit with administration of GC within these populations exists;
      however, data are sparse and often conflicting. ADVERSE EFFECTS AND
      CONTRAINDICATIONS: Routine use of GC in some conditions such as trauma,
      hemorrhagic shock, and traumatic brain injury is likely contraindicated. GC use
      has been associated with hyperglycemia, pneumonia, urinary tract infection,
      gastrointestinal ulceration, or increased mortality in some populations.

PMID- 28449320
TI  - A randomised, double-blind, trial of the safety and efficacy of omarigliptin (a
      once-weekly DPP-4 inhibitor) in subjects with type 2 diabetes and renal
      impairment.
AB  - AIMS: To assess the safety and efficacy of omarigliptin in subjects with type 2
      diabetes mellitus (T2DM) and chronic renal impairment (RI). METHODS: Patients
      with T2DM with moderate RI (estimated glomerular filtration rate [eGFR] >=30 to
      <60 mL/min/1.73 m2 ) (N=114), severe RI (eGFR <30 mL/min/1.73 m2 ) (N=55) or end
      stage renal disease on dialysis (N=44), who were either not on an
      antihyperglycaemic agent therapy for at least 12 weeks at screening, washed-off
      of oral antihyperglycaemic agent monotherapy or low-dose dual combination
      therapy, or on insulin monotherapy, with baseline glycated haemoglobin (HbA1c) of
      6.5%-10.0% were randomised to omarigliptin or to placebo for 24 weeks (primary
      end-point) followed by a 30-week period with subjects on placebo switched to
      blinded glipizide (if not on insulin). RESULTS: After 24 weeks, from a mean
      baseline HbA1c of 8.4% in the omarigliptin group and 8.3% in the placebo group,
      the least squares mean (95% CI) change from baseline in HbA1c in the overall
      population (all renal strata combined) was -0.77% (-1.00 to -0.54) in the
      omarigliptin group and -0.44% (-0.67 to -0.21) in the placebo group; between
      group difference of -0.33% (-0.63 to -0.02); P=0.035. After 24 weeks, the
      incidences of subjects with symptomatic hypoglycaemia, one or more adverse event
      (AE), drug-related AE, serious AE and discontinuation due to an AE were similar
      in the omarigliptin and placebo groups. CONCLUSIONS: In this study in subjects
      with T2DM and RI, relative to placebo, omarigliptin provided clinically
      meaningful reductions in HbA1c, had a similar incidence of symptomatic
      hypoglycaemia and was generally well tolerated.

PMID- 28449322
TI  - A bacterium with close genetic identity to Pseudomonas mandelii associated with
      spring fish kills in wild bluegill Lepomis macrochirus Rafinesque and pumpkinseed
      sunfish Lepomis gibbosus (Linnaeus).
AB  - Pseudomonas fluorescens are known bacterial pathogens in fish. The P. fluorescens
      group contains at least nine different bacterial species, although species from
      fish have rarely been differentiated. Two isolated fish kills affecting wild
      bluegills, Lepomis macrochirus Rafinesque, and pumpkinseed sunfish, Lepomis
      gibbosus (Linnaeus), occurred in the spring of 2015 during cool water
      temperatures (12.5 degrees C-15.5 degrees C). Disease signs included severe
      bacteraemia with rare gross external signs. Pure bacterial cultures isolated from
      kidneys of all affected fish were identified as P. fluorescens using the API 20NE
      system, while no bacteria were isolated from asymptomatic fish. To further
      identify the species of bacterium within the P. fluorescens complex, genetic
      analysis of the 16S rRNA, rpoD and gyrB genes was conducted. DNA sequences of
      bacterial isolates from both mortality events were identical and had close
      identity (>=99.7%) to Pseudomonas mandelii. Although likely widespread in the
      aquatic environment, this is the first report of a bacterium closely resembling
      P. mandelii infecting and causing disease in fish. The bacterium grew at
      temperatures between 5 degrees C and 30 degrees C, but not at 37 degrees C. It is
      possible that infections in fish were a result of immunosuppression associated
      with spring conditions combined with the psychrotrophic nature of the bacterium.

PMID- 28449323
TI  - In vitro comparison of renal stone laser treatment using fragmentation and
      popcorn technique.
AB  - OBJECTIVE: To study the effectiveness of two laser techniques clinically used to
      fragment renal stones: fragmenting technique (FT) and popcorn technique (PT).
      METHODS: Phantom stones were placed in a test tube filled with water, mimicking a
      renal calyx model. A Holmium:YAG laser was used for fragmentation using both
      techniques. Four series of experiments were performed with two parameters: the
      technique (FT or PT) and the number of stones in the test tube (one or four). The
      mass decrease of the phantom stones was measured before, during, and after the
      experiment to quantify the effect of both techniques. RESULTS: Visualization of
      PT showed that the main effect of PT takes place, when the stone moves in front
      of the laser fiber and is subject to direct radiant exposure. Both FT and PT
      resulted in a decrease in stone weight; the mass decrease of the stones subjected
      to FT exceeded that of the stones subjected to PT, even with less laser energy
      applied. This difference in mass decrease was evident in both the experiments
      with one and four stones. CONCLUSIONS: PT was less effective in decreasing stone
      weight compared with FT. The FT is more effective regarding the applied energy
      than PT, even in a shorter time period and regardless of the number of stones.
      This study suggests that FT is to be preferred over PT, when stones are
      accessible by the laser fiber. Lasers Surg. Med. 49:698-704, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28449325
TI  - Electrosynthesis of Bifunctional WS3-x /Reduced Graphene Oxide Hybrid for
      Hydrogen Evolution Reaction and Oxygen Reduction Reaction Electrocatalysis.
AB  - A multitude of research into the application of transition-metal dichalcogenides
      as earth-abundant hydrogen evolution reaction (HER) electrocatalysts has been
      conducted. However, current synthetic methods generally deploy environmentally
      harmful chemicals and energy-consuming reaction conditions, despite the primary
      intent to attain renewable energy production. Here, the desirable properties of
      tungsten sulfide and reduced graphene oxide (rGO) have been combined and hybrid
      materials have been fabricated through simultaneous electrochemical reduction and
      synthesis, as a versatile and environmentally benign alternative to conventional
      fabrication techniques. Through concurrent studies of three rGO materials, the
      precursor of which was graphene oxide (GO), produced by Hummers, Staudenmaier, or
      Hofmann oxidation methods, the importance of the choice of oxidation method
      employed prior to the fabrication of the hybrid was shown. In this cardinal
      study, a mixed WS2 /WS3 film-like material (WS3-x ) was synthesized directly onto
      GO-modified glassy carbon electrodes by cyclic voltammetry and the resultant
      hybrid materials (WS3-x /rGO) were thoroughly characterized by SEM, energy
      dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and Raman
      spectroscopy. The excellent bifunctional electrocatalytic performances of WS3-x
      /rGO towards both HER and oxygen reduction reaction stemmed from the coupled
      impacts of amplified electrical conductivity and surface area of rGO; the
      presence of metallic species within rGO, resulting from the oxidation process;
      and the amount of WS3-x successfully electrodeposited in the hybrid. The
      efficacious fabrication of the WS3-x /rGO composite through electrosynthesis
      reveals an innovative and eco-friendly methodology for the development of cost
      effective and highly active bifunctional electrocatalysts for renewable energy
      generation.

PMID- 28449324
TI  - Efficacy and safety of lixisenatide in patients with type 2 diabetes and renal
      impairment.
AB  - AIMS: This post hoc assessment evaluated the efficacy and safety of once-daily,
      prandial glucagon-like peptide-1 receptor agonist lixisenatide in patients with
      type 2 diabetes (T2D) and normal renal function (estimated glomerular filtration
      rate >=90 mL/min), or mild (60-89 mL/min) or moderate (30-59 mL/min) renal
      impairment. METHODS: Patients from 9 lixisenatide trials in the GetGoal clinical
      trial programme were categorized by baseline creatinine clearance: normal renal
      function (lixisenatide n = 2094, placebo n = 1150); renal impairment (mild:
      lixisenatide n = 637, placebo n = 414; moderate: lixisenatide n = 122, placebo n
      = 68). Meta-analyses of placebo-adjusted mean differences between baseline renal
      categories were performed for efficacy and safety outcomes. RESULTS: HbA1c, 2
      hour postprandial plasma glucose and fasting plasma glucose were comparably
      reduced in lixisenatide-treated patients with normal renal function, and mild and
      moderate renal impairment. The most common adverse events (AEs) in all renal
      function categories were gastrointestinal (GI), predominantly nausea and
      vomiting. A 14% higher incidence of GI AEs and a 10% higher incidence of nausea
      and vomiting were seen with mild impairment vs normal function (P = .003 for
      both), but no significant differences were observed between the mild and moderate
      impairment categories (P = .99 and P = .57, respectively), or between the
      moderate impairment and normal categories (P = .16 and P = .65, respectively).
      Additionally, the incidence of hypoglycaemia was similar in all categories.
      CONCLUSIONS: This study demonstrates that baseline renal status does not affect
      efficacy outcomes in lixisenatide- vs placebo-treated patients, and that no
      lixisenatide dose adjustment is required for patients with T2D with mild or
      moderate renal impairment.

PMID- 28449326
TI  - Area-wide mass trapping by pheromone-based attractants for the control of sugar
      beet weevil (Bothynoderes punctiventris Germar, Coleoptera: Curculionidae).
AB  - BACKGROUND: Owing to the changing climate, narrow crop rotation, and changes in
      insecticide application practice, sugar beet weevil (SBW) (Bothynoderes
      punctiventris Germar) has become the most important economic pest in sugar beet.
      To develop alternative control methods, an area-wide (AW) control program using
      aggregation pheromones was implemented over 4 years on an area of 6 and 14.8 km2
      in east Croatia. RESULTS: The mass trapping of SBW on the 'old' sugar beet fields
      reduced the population from 0.73% to 11.59%. Owing to the strong attack, mass
      trapping was not effective enough to avoid an insecticide application. However,
      it significantly reduced the number of insecticide applications, the amount of
      insecticide used, and the damage compared to the fields outside the mass trapping
      area. CONCLUSION: This is the first study to implement an AW program for SBW. It
      may not be possible to state from this study that trapping alone can reduce the
      SBW population below the economic threshold level. However, the data do suggest
      that trapping can play an important role in the reduction of insecticide
      applications and in creating an integrated pest management plan for dealing with
      SBW under similar circumstances. (c) 2017 Society of Chemical Industry.

PMID- 28449327
TI  - Skeletal muscle IL-15/IL-15Ralpha and myofibrillar protein synthesis after
      resistance exercise.
AB  - In vitro and in vivo studies described the myokine IL-15 and its receptor IL
      15Ralpha as anabolic/anti-atrophy agents, however, the protein expression of IL
      15Ralpha has not been measured in human skeletal muscle and data regarding IL-15
      expression remain inconclusive. The purpose of the study was to determine serum
      and skeletal muscle IL-15 and IL-15Ralpha responses to resistance exercise
      session and to analyze their association with myofibrillar protein synthesis
      (MPS). Fourteen participants performed a bilateral leg resistance exercise
      composed of four sets of leg press and four sets of knee extension at 75% 1RM to
      task failure. Muscle biopsies were obtained at rest, 0, 4 and 24 hours post
      exercise and blood samples at rest, mid-exercise, 0, 0.3, 1, 2, 4 and 24 hours
      post-exercise. Serum IL-15 was increased by ~5.3-fold immediately post-exercise,
      while serum IL-15Ralpha decreased ~75% over 1 hour post-exercise (P<.001).
      Skeletal muscle IL-15Ralpha mRNA and protein expression were increased at 4 hours
      post-exercise by ~2-fold (P<.001) and ~1.3-fold above rest (P=.020),
      respectively. At 24 hours post-exercise, IL-15 (P=.003) and IL-15Ralpha mRNAs
      increased by ~2-fold (P=.002). Myofibrillar fractional synthetic rate between 0-4
      hours was associated with IL-15Ralpha mRNA at rest (r=.662, P=.019), 4 hours
      (r=.612, P=.029), and 24 hours post-exercise (r=.627, P=.029). Finally, the
      muscle IL-15Ralpha protein up-regulation was related to Leg press 1RM (r=.688,
      P=.003) and total weight lifted (r=.628, P=.009). In conclusion, IL-15/IL
      15Ralpha signaling pathway is activated in skeletal muscle in response to a
      session of resistance exercise.

PMID- 28449328
TI  - Lepromatous Leprosy in a Renal Transplant Recipient.

PMID- 28449329
TI  - Valuing productivity costs using the friction-cost approach: Estimating friction
      period estimates by occupational classifications for the UK.
AB  - The friction cost approach has been proposed as an alternative to the human
      capital approach in estimating productivity costs. However, it is difficult, in
      practice, to apply this approach due to limited availability of context-specific
      data. Using national and firm-level data on vacancy durations sourced from 4
      organisations, we estimated vacancy durations, and consequently, length of
      friction period for the United Kingdom disaggregated by occupational
      classification. We found comparable estimates to previously reported friction
      periods elsewhere. The disaggregated friction period analysis confirmed
      occupational class has an effect on the estimated length of the friction period.
      The research presents estimates on vacancy durations and friction periods
      necessary to use the friction cost approach in a practical way in economic
      evaluations.

PMID- 28449330
TI  - Exploring the experience of nurse practitioners who have committed medical
      errors: A phenomenological approach.
AB  - BACKGROUND AND PURPOSE: To explore the experience of committing medical error
      from the perspective of nurse practitioners (NPs). Overall, the purpose of the
      study is to discern NPs' behaviors, perceptions, and coping mechanisms in
      response to having made a medical error. METHODS: Qualitative research based on
      two face-to-face audio-recorded semistructured interviews with 10 NPs who had
      made medical errors in practice. The analysis was guided by concepts in
      phenomenology. CONCLUSIONS: During iterative analyses, four overarching themes
      were identified: (a) The paradox of error victimization, (b) primacy of
      responsibility and mindfulness, (c) yearning for forgiveness and a supportive
      other, and (d) coping with a new reality is context dependent. The narratives
      strongly suggest that NPs who err experience "second victim" phenomena.
      IMPLICATIONS FOR PRACTICE: Reminiscing about the experience of living through an
      error, NPs shared meaningful insights into their need for a safe environment in
      which they could candidly share feelings, reflect on the experience, and
      ascertain the etiology of the mistake. Debriefing in a formal manner might
      prevent the development of permanent psychological injuries. Hence, inherent to
      the care of "second victims" is the notion of co-workers' fairness, compassion,
      and recognition of appropriate caring responses that contribute to effective
      coping and healing.

PMID- 28449331
TI  - miR-130A as a diagnostic marker to differentiate malignant mesothelioma from lung
      adenocarcinoma in pleural effusion cytology.
AB  - BACKGROUND: Malignant pleural mesothelioma is a rare tumor with a dismal
      prognosis, usually presenting with recurrent effusions. However, the majority of
      malignant pleural effusions are due to lung adenocarcinoma (AdC). The distinction
      between these tumors has considerable therapeutic and medicolegal implications
      and can be very challenging both histologically and cytologically. Appropriate
      immunohistochemistry (IHC) is required to support the diagnosis. MicroRNA (miRNA)
      expression analysis could be a viable diagnostic tool for distinguishing between
      these tumors. The purpose of the current study was to assess the reliability of
      miRNAs as diagnostic markers to differentiate epithelioid malignant mesothelioma
      (MM) from lung AdC. METHODS: Bioinformatic analysis of publicly searchable data
      sets regarding miRNA expression profiling was performed to select the most
      significant differentially expressed miRNAs. These were analyzed by quantitative
      polymerase chain reaction on histologic (41 MM cases and 40 lung AdC cases) and
      cytological (26 MM cases and 27 lung AdC cases) specimens and the diagnostic
      performances were assessed. RESULTS: miR-130a, miR-193a, miR-675, miR-141, miR
      205, and miR-375 were found to be the best distinguishing markers. Of these, only
      miR-130a was significantly overexpressed in MM compared with lung AdC (P =.029 in
      histologic and P =.014 in cytological samples). miR-130a demonstrated a
      sensitivity of 77%, a specificity of 67%, a positive predictive value of 69%, a
      negative predictive value of 75%, and an accuracy of 72% in identifying MM.
      CONCLUSIONS: The diagnostic performances of miR-130a expression analysis and IHC
      appear to be similar. miR-130a quantification could be used reliably as second
      level diagnostic tool to differentiate MM from lung AdC in pleural effusion
      cytology, mainly in those cases with ambiguous or negative IHC. Further
      validation is needed. Cancer Cytopathol 2017;125:635-43. (c) 2017 American Cancer
      Society.

PMID- 28449333
TI  - Inheritance and the sunshine vitamin.

PMID- 28449332
TI  - Behavioural disinhibition in the general population during the antiretroviral
      therapy roll-out in Sub-Saharan Africa: systematic review and meta-analysis.
AB  - OBJECTIVES: Improved life expectancy and reduced transmission probabilities due
      to ART may result in behavioural disinhibition - that is an increase in sexual
      risk behaviour in response to a perceived lower risk of HIV. We examined trends
      in sexual risk behaviour in the general population of sub-Saharan African
      countries 1999-2015. METHODS: We systematically reviewed scientific literature of
      sexual behaviour and reviewed trends in Demographic and Health Surveys. A meta
      analysis on four indicators of sexual risk behaviour was performed: unprotected
      sex, multiple sexual partners, commercial sex and prevalence of sexually
      transmitted infections. RESULTS: Only two peer-reviewed studies met our inclusion
      criteria, while our review of DHS data spanned 18 countries and 16 years (1999
      2015). We found conflicting trends in sexual risk behaviour. Reported unprotected
      sex decreased consistently across the 18 countries, for both sexes. In contrast,
      reporting multiple partners was decreasing over the period 1999 to the mid-2000s,
      yet has been consistently increasing thereafter. Similar trends were found for
      reported sexually transmitted infections and commercial sex (men only).
      CONCLUSIONS: In conclusion, we found no clear evidence of behavioural
      disinhibition due to expanded access to ART in sub-Saharan Africa. Substantial
      increases in condom use coincided with increases in reported multiple partners,
      commercial sex and sexually transmitted infections, especially during the period
      of ART scale-up. Further research is needed into how these changes might affect
      HIV transmission.

PMID- 28449335
TI  - Factors affecting blood glucose screening in the elderly with special reference
      to physical activity.

PMID- 28449337
TI  - Gastrointestinal: Enema nozzle injury to the rectum, a vague presentation with
      significant morbidity.

PMID- 28449336
TI  - Gastrointestinal: Severe congestive heart failure and acute gastric mucosal
      necrosis.

PMID- 28449338
TI  - Metformin use and the risk of colorectal adenoma: A systematic review and meta
      analysis.
AB  - BACKGROUND AND AIM: Although it is known that metformin can reduce risk of
      colorectal cancer, it is unclear whether it protects against colorectal adenoma.
      METHODS: This study conducted a systematic literature search on MEDLINE, EMBASE,
      and the Cochrane Library using the primary keywords "colorectal," "colon,"
      "rectal," "rectum," "adenoma," "polyp," "neoplasia," "neoplasm," "metformin," and
      "diabetes." Studies were included if they evaluated the association between
      metformin use and colorectal adenoma and reported odds ratios (ORs) or provided
      data from which these could be estimated. RESULTS: Ten studies and a total of
      8726 patients were evaluated. Across all studies, a median of 32.1% (range: 15.2
      53.0%) of patients taking metformin also had adenoma; a median of 43.5% (range:
      20.5-59.6%) of those not taking metformin had adenoma. In our meta-analysis,
      metformin use reduced the risk of adenoma (pooled OR = 0.76, 95% confidence
      interval [CI] = 0.63-0.92, I2  = 60%). Upon subgroup analyses, metformin use
      tended to reduce risk of adenoma in a high-risk population consisting of patients
      with a history of colorectal neoplasia (CRN) (pooled OR = 0.61, 95% CI = 0.34
      1.10, I2  = 79%). In addition, metformin reduced the risk of adenoma in a high
      risk population consisting of patients with diabetes mellitus (pooled OR = 0.75,
      95% CI = 0.62-0.91, I2  = 57%). CONCLUSION: Metformin use seemed to be associated
      with a reduced risk of colorectal adenoma, especially in high-risk populations
      consisting of patients with diabetes mellitus or a history of CRN, although
      statistical power was not achieved in patients with a history of CRN.

PMID- 28449339
TI  - Hepatobiliary and Pancreatic: Unusual cause of acute pancreatitis.

PMID- 28449340
TI  - Identifying the optimal strategy for screening of advanced colorectal neoplasia.
AB  - BACKGROUND AND AIM: To guide selection of optimal screening strategies for
      advanced colorectal neoplasia (ACRN), we evaluated the screening performances of
      sigmoidoscopy, fecal immunochemical test (FIT), and the Asia-Pacific Colorectal
      Screening (APCS) system, as well as combinations of these techniques. METHODS: We
      reviewed the records of participants who had undergone a colonoscopy and FIT as
      part of a comprehensive health-screening program. Results of sigmoidoscopy were
      estimated from lesions under colonoscopic examination. The screening strategies
      were classified as sigmoidoscopy-based, FIT-based, and APCS-based. The
      sensitivity and reduction of number needed to colonoscope (NNScope) of each
      screening strategy were assessed. RESULTS: Of 23 023 participants, 398 (1.7%) had
      ACRN. To predict the presence of ACRN, sigmoidoscopy was the most effective
      method (odds ratio [OR]: 22.96, 95% confidence interval [CI]: 18.26-29.07),
      followed by FIT (OR: 7.18, 95% CI: 5.28-9.68) and APCS (high risk [>=4] OR: 2.59,
      95% CI: 1.87-3.58; moderate risk [2-3] OR: 1.66, 95% CI: 1.28-2.17). Regarding
      sigmoidoscopy-based strategies, "sigmoidoscopy positive alone" and "sigmoidoscopy
      positive or APCS >=4" were optimal strategies (reduction of NNScope: 79-86%;
      sensitivity: 73-78%). In the case of FIT-based strategies, "FIT positive or APCS
      >=4" was the optimal strategy (reduction of NNScope: 72%; sensitivity: 37%). With
      regard to the APCS system only, "APCS >=2" and "APCS >=4" were recommended as
      sensitivity-preferred and reduction in NNScope-preferred strategies,
      respectively. CONCLUSIONS: The performance in ACRN prediction differs among
      screening methods (sigmoidoscopy, FIT, and APCS). Among the various single or
      combined screening strategies, several specific strategies can be chosen
      depending on medical resources, financial budgets, and screenee preference.

PMID- 28449341
TI  - Gastrointestinal: Idiopathic granulomatous gastritis observed by magnifying
      narrow-band imaging endoscopy.

PMID- 28449342
TI  - Gastrointestinal: Gastric perforation during esophageal endoscopic submucosal
      dissection: A serious adverse event in a patient with esophageal stricture.

PMID- 28449343
TI  - Cost-effectiveness of the highly effective direct-acting antivirals in the
      treatment of chronic hepatitis C in Hong Kong.
AB  - BACKGROUND AND AIM: In Asia-Pacific where cost is a major concern, peginterferon
      plus ribavirin (PR) often remain as the standard of care in chronic hepatitis C
      (CHC) treatment, while the direct-acting antivirals (DAAs) are commonly
      recommended as retreatment. Newer DAAs can achieve a sustained virological
      response (SVR) of nearly 100% with pan-genotypic coverage, that is "Highly
      Effective DAAs." We aimed to investigate the most desirable cost range for the
      Highly Effective DAAs using Hong Kong as an example. METHODS: Markov modeling was
      performed using PR as the reference strategy. The cost-effectiveness of the
      Highly Effective DAAs was compared with sofosbuvir-PR (first-line and rescue) and
      boceprevir-PR therapies. A 50-year-old genotype 1b hepatitis C virus (HCV)
      infected treatment-naive patient with METAVIR F3 was used as the base case
      scenario to reflect the commonest HCV genotype in Hong Kong. RESULTS: The use of
      PR would incur a lifetime cost of US$35,854 and effectiveness of 14.85 quality
      adjusted life-year (QALY). Sofosbuvir-PR as first-line treatment was dominated by
      other regimes. If Sofosbuvir-PR rescue therapy was used, the drug cost of Highly
      Effective DAAs should be set below US$43,553, with a cost-effectiveness ratio
      (CER) of US$3035/QALY compared with PR. In regions where Boceprevir-PR was still
      used as first-line therapy, the desirable drug cost of Highly Effective DAAs
      would be below US$56,985 to achieve a CER of US$5427/QALY. CONCLUSIONS: The most
      desirable costs of the Highly Effective DAAs would be below US$43,553 if
      Sofosbuvir-PR rescue therapy is used and below US$56,985 if Boceprevir-PR therapy
      is used.

PMID- 28449344
TI  - Endoscopic features and genetic background of inflammatory bowel disease
      complicated with Takayasu arteritis.
AB  - BACKGROUND AND AIM: Takayasu arteritis (TA) is occasionally complicated with
      inflammatory bowel disease (IBD). This study assessed the endoscopic and genetic
      features of IBD complicated with TA (IBD-TA). METHODS: This study retrospectively
      reviewed the clinical charts of 142 TA patients (14 men and 128 women; median age
      48.5 years [range, 18-97 years]). Human lymphocyte antigen (HLA) types and a
      single-nucleotide polymorphism rs6871626 in the IL12B gene were assessed in 101
      and 81 patients with TA, respectively. RESULTS: Inflammatory bowel disease was
      diagnosed in 13 (9.2%) of the 142 patients. The endoscopic features of IBD-TA at
      initial diagnosis (n = 8) showed discontinuous and focal mucosal inflammations (n
      = 7, 87.5%), and only one case was diagnosed as ulcerative colitis (UC) at the
      first colonoscopy. In the genetic comparison of HLA class I between TA patients
      with IBD and those without IBD, HLA-B*52:01 and C*12:02 were more frequent in the
      IBD-TA group (P = 0.001 and P = 0.009, respectively). Meanwhile, HLA-DRB-1*15:02,
      DQA-1*01:03, DQB-1*06:01, and DPB-1*09:01 as HLA class II were positively
      associated with IBD-TA (P = 0.004, P = 0.019, P = 0.019, and P = 0.002,
      respectively). IL12B rs6871626 did not show an association with IBD-TA compared
      with that with TA without IBD. CONCLUSIONS: The endoscopic findings of IBD-TA at
      initial diagnosis were atypical for UC or Crohn's disease. IBD-TA possessed the
      HLA haplotype, which had a susceptible effect on UC.

PMID- 28449345
TI  - Proton pump inhibitors do not increase the risk for recurrent spontaneous
      bacterial peritonitis in patients with cirrhosis.
AB  - BACKGROUND AND AIM: The present study aimed to assess the real impact of proton
      pump inhibitor (PPI) use on incidence of recurrent spontaneous bacterial
      peritonitis (SBP) in a homogenous population composed of cirrhotic patients with
      a previous SBP where differences related with SBP incidence between PPI users and
      non-users are less likely to exist. METHODS: This retrospective cohort study
      enrolled 307 cirrhotic patients taking diuretics for ascites control and had a
      previous SBP. Patients who took any PPI for at least 1 week prior to a second SBP
      were included in the PPI group. The incidence of a second SBP was a primary
      outcome and was compared between PPI group and non-PPI group before and after
      propensity score matching. Risk factors for a second SBP were investigated by
      multivariate analysis. RESULTS: Second SBP occurred in 17 patients (29.3%) during
      mean 52.1 +/- 5.2 months of PPI group and in 60 patients (24.1%) during mean 61.9
      +/- 4.8 months of non-PPI group, which did not differ (P = .185). In the matched
      cohort, second SBP similarly occurred in both groups [29.3% of PPI group vs 26.8%
      of non-PPI group (P = .271)]. According to the multivariate analysis, Child-Pugh
      score was the only significant risk factor for a second SBP (hazard ratio 1.68,
      95% confidence interval, 1.13-2.50, P = .001). Isolated bacteria and clinical
      outcomes such as of mortality, presence of sepsis, and hospital stay did not
      differ between the two groups in the matched cohort. CONCLUSION: Proton pump
      inhibitor use is not a risk factor for recurrent SBP in cirrhotic patients.

PMID- 28449346
TI  - Airborne allergic contact dermatitis caused by isothiazolinones in water-based
      paints: a retrospective study of 44 cases.
AB  - BACKGROUND: Airborne allergic contact dermatitis caused by paints containing
      isothiazolinones has been recognized as a health hazard. OBJECTIVES: To collect
      epidemiological, clinical and patch test data on airborne allergic contact
      dermatitis caused by isothiazolinone-containing paints in France and Belgium.
      METHODS: A descriptive, retrospective study was initiated by the Dermatology and
      Allergy Group of the French Society of Dermatology, including
      methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI)- and/or MI
      sensitized patients who developed airborne allergic contact dermatitis following
      exposure to isothiazolinone-containing paint. RESULTS: Forty-four cases were
      identified, with mostly non-occupational exposure (79.5%). Of the patients, 22.5%
      of also had mucosal symptoms. In several cases, the dermatitis required systemic
      corticosteroids (27.3%), hospitalization (9.1%), and/or sick leave (20.5%). A
      median delay of 5.5 weeks was necessary to enable patients to enter a freshly
      painted room without a flare-up of their dermatitis. Approximately one-fifth of
      the patients knew that they were allergic to MI and/or MCI/MI before the exposure
      to paints occurred. CONCLUSION: Our series confirms that airborne allergic
      contact dermatitis caused by paints containing isothiazolinones is not rare, and
      may be severe and long-lasting. Better regulation of isothiazolinone
      concentrations in paints, and their adequate labelling, is urgently needed.

PMID- 28449347
TI  - Caregiving for Older Adults with Obesity in the United States.
AB  - OBJECTIVES: To determine the difference in receipt of activity of daily living
      (ADL) assistance between obese and normal-weight older adults. DESIGN:
      Retrospective cohort study. SETTING: National Health and Aging Trends Study, 2011
      2015. PARTICIPANTS: U.S. adults aged 65 and older with ADL disability and a body
      mass index (BMI) of 18.5 kg/m2 or greater (N = 5,612) MEASUREMENTS: BMI was
      classified as normal weight (18.5-24.9 kg/m2 ), overweight (25.0-29.9 kg/m2 ), or
      obese (>=30.0 kg/m2 ). Primary outcome was self-reported receipt of help with
      specific ADLs. Models were adjusted for demographic characteristics (age, sex,
      race), degree of need (self-reported general health, severity of disability),
      household resources (income, marriage, people in household, number of children),
      and cognitive status (dementia, proxy respondent). RESULTS: Obese with
      disabilities had lower rates of receiving assistance with walking inside (odds
      ratio (OR) = 0.63, 95% confidence interval (CI) = 0.50-0.81), walking outside (OR
      = 0.76, 95% CI = 0.59-0.97), toileting (OR = 0.68, 95% CI = 0.52-0.89), and
      getting in and out of bed (OR = 0.67, 95% CI = 0.50-0.87) than normal-weight
      older adults after adjustment for respondent demographic characteristics. Level
      of need and cognitive status partially explained the associations. In fully
      adjusted models, older adults with obesity still had significantly lower odds of
      receiving assistance in getting in and out of bed than normal weight adults (OR =
      0.69, 95% CI = 0.49-0.98). CONCLUSION: Older adults with obesity are less likely
      to receive assistance for ADL disabilities than their normal-weight counterparts
      an important concern because of ongoing demographic changes in the United States.

PMID- 28449348
TI  - Thienylquinonoidal Porphyrins and Hexaphyrins with Singlet Diradical Ground
      States.
AB  - To explore stable organic diradicaloids, meso-thienylquinonoid-substituted
      porphyrins Pn and hexaphyrins Hn, where "n" denotes the number of thienyl units
      in the meso-substituents, were synthesized. P0 was identified as a closed-shell
      quinonoid, whereas P1 was shown to possess significant diradical character with
      diradical character index (y) of 0.99 and quite small singlet-triplet energy gap
      (DeltaES-T ) of -0.13 kcal mol-1 . P1 was certainly stable, allowing its
      isolation, but decomposed gradually in solution. In the hexaphyrin series, it was
      shown that H0 and H1 were closed-shell quinonoids, but H2 was a highly stable
      diradicaloid with y=0.85 and DeltaES-T of -3.72 kcal mol-1 . The high stability
      of H2 was ascribed to effective spin delocalization over the entire conjugated
      network. Characteristically, H2 displays an intense absorption band in NIR region
      at lambdamax =1175 nm with molar absorption coefficient (epsilon) of 8.81*104 
      mol-1  L cm-1 , a narrow HOMO-LUMO gap of 0.69 eV, and nine reversible redox
      potential waves.

PMID- 28449349
TI  - Effector mechanisms of IgA antibodies against CD20 include recruitment of myeloid
      cells for antibody-dependent cell-mediated cytotoxicity and complement-dependent
      cytotoxicity.

PMID- 28449350
TI  - Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting
      highly immunized patients.
AB  - BACKGROUND: Highly immunized patients are a challenge for organ transplantation
      programs. One way of increasing the likelihood of transplantation in this group
      of patients is to expand the possible donations by defining acceptable HLA
      mismatches. In the Scandiatransplant Acceptable Mismatch Program (STAMP), a de
      centralized approach has been implemented in 2009. AIMS: The program has been
      improved during the years from utilizing HLA-A, -B, -DR matching only to include
      typing of all deceased donors for HLA-A, -B, -C, -DRB1 and -DQB1. The calculation
      of a transplantability score (TS) has been introduced in order to take both HLA
      and AB0 into consideration resulting in a more realistic picture of the
      transplantability chance. MATERIALS AND METHODS: Patients were selected for
      eligibility and results of immunisation status were prepared in each of the 9
      tissue typing laboratories, while access to the program is finally governed by a
      common steering group of immunologists and clinicians. RESULTS: In the period
      from March 2009 until February 2015, 96 patients were transplanted within this
      program. The mean recipient age was 49 years and 57% were females, 30% of the
      patients were first transplants and of these 93% were females. The majority of
      the patients had 2-5 HLA-A, -B. -DR mismatches. The allograft survival at 60
      months was 79.1%. Applying the TS to the cohort confirmed that patients with a
      low TS score had longer waiting times. CONCLUSION: The program has matured during
      the years and now proves to be a valid approach for transplanting highly
      immunized patients.

PMID- 28449352
TI  - Effectiveness and Safety of Intrathecal Ziconotide: Interim Analysis of the
      Patient Registry of Intrathecal Ziconotide Management (PRIZM).
AB  - BACKGROUND: The Patient Registry of Intrathecal Ziconotide Management (PRIZM)
      evaluated long-term effectiveness, safety, and tolerability of intrathecal
      ziconotide treatment in clinical practice. METHODS: Patient Registry of
      Intrathecal Ziconotide Management was an open-label, long-term, multicenter,
      observational study of adult patients with severe chronic pain. This interim
      analysis (data through July 10, 2015) of ziconotide as the first vs. not first
      intrathecal agent in pump included change from baseline in the Numeric Pain
      Rating Scale (NPRS; primary efficacy measure) and Patient Global Impression of
      Change (PGIC) scores. RESULTS: Enrollment closed at 93 patients; data collection
      was ongoing at the time of this interim analysis. Fifty-one patients (54.8%)
      received ziconotide as the first agent in pump (FIP+), whereas 42 (45.2%) did not
      (FIP-). Mean (SD) baseline NPRS scores were 7.4 (1.9) and 7.9 (1.6) in FIP+ and
      FIP- patients, respectively. Mean (SEM) percentage changes in NPRS scores were 
      29.4% (5.5%) in FIP+ patients (n = 26) and +6.4% (7.7%) in FIP- patients (n = 17)
      at month 6 and -34.4% (9.1%) in FIP+ patients (n = 14) and -3.4% (10.2%) in FIP-
      patients (n = 9) at month 12. Improvement from baseline, measured by PGIC score,
      was reported in 69.2% of FIP+ (n = 26) and 35.7% of FIP- (n = 14) patients at
      month 6 and 85.7% of FIP+ (n = 7) and 71.4% of FIP- (n = 7) patients at month 12.
      The most common adverse events (>= 10% of patients overall as of the data cut)
      were nausea (19.6% vs. 7.1% of FIP+ vs. FIP- patients, respectively), confusional
      state (9.8% vs. 11.9%), and dizziness (13.7% vs. 7.1%). CONCLUSIONS: Greater
      improvements in efficacy outcomes were observed when ziconotide was initiated as
      first-line intrathecal therapy vs. not first intrathecal agent in pump. The
      adverse event profile was consistent with the ziconotide prescribing information.

PMID- 28449351
TI  - Long-term plasticity of corticostriatal synapses is modulated by pathway-specific
      co-release of opioids through kappa-opioid receptors.
AB  - KEY POINTS: Both endogenous opioids and opiate drugs of abuse modulate learning
      of habitual and goal-directed actions, and can also modify long-term plasticity
      of corticostriatal synapses. Striatal projection neurons of the direct pathway co
      release the opioid neuropeptide dynorphin which can inhibit dopamine release via
      kappa-opioid receptors. Theta-burst stimulation of corticostriatal fibres
      produces long-term potentiation (LTP) in striatal projection neurons when
      measured using whole-cell patch recording. Optogenetic activation of direct
      pathway striatal projection neurons inhibits LTP while reducing dopamine release.
      Because the endogenous release of opioids is activity dependent, this modulation
      of synaptic plasticity represents a negative feedback mechanism that may limit
      runaway enhancement of striatal neuron activity in response to drugs of abuse.
      ABSTRACT: Synaptic plasticity in the striatum adjusts behaviour adaptively during
      skill learning, or maladaptively in the case of addiction. Just as dopamine plays
      a critical role in synaptic plasticity underlying normal skill learning and
      addiction, endogenous and exogenous opiates also modulate learning and addiction
      related striatal plasticity. Though the role of opioid receptors in long-term
      depression in striatum has been characterized, their effect on long-term
      potentiation (LTP) remains unknown. In particular, direct pathway (dopamine D1
      receptor-containing; D1R-) spiny projection neurons (SPNs) co-release the opioid
      neuropeptide dynorphin, which acts at presynaptic kappa-opioid receptors (KORs)
      on dopaminergic afferents and can negatively regulate dopamine release.
      Therefore, we evaluated the interaction of co-released dynorphin and KOR on
      striatal LTP. We optogenetically facilitate the release of endogenous dynorphin
      from D1R-SPNs in brain slice while using whole-cell patch recording to measure
      changes in the synaptic response of SPNs following theta-burst stimulation (TBS)
      of cortical afferents. Our results demonstrate that TBS evokes corticostriatal
      LTP, and that optogenetic activation of D1R-SPNs during induction impairs LTP.
      Additional experiments demonstrate that optogenetic activation of D1R-SPNs
      reduces stimulation-evoked dopamine release and that bath application of a KOR
      antagonist provides full rescue of both LTP induction and dopamine release during
      optogenetic activation of D1R-SPNs. These results suggest that an increase in the
      opioid neuropeptide dynorphin is responsible for reduced TBS LTP and illustrate a
      physiological phenomenon whereby heightened D1R-SPN activity can regulate
      corticostriatal plasticity. Our findings have important implications for learning
      in addictive states marked by elevated direct pathway activation.

PMID- 28449353
TI  - How excluding some benefits from value assessment of new drugs impacts
      innovation.
AB  - Payers often assess the benefits of new drugs relative to costs for reimbursement
      purposes, but they frequently exclude some drugs' option-related benefits,
      reducing their reimbursement chances, and making them less attractive R&D
      investments. We develop and test a real options model of R&D investment that
      shows that excluding option-related benefits heightens drug developers'
      incentives to avoid high-risk (volatile) R&D investments and instead encourages
      them to focus on "safer" (positively skewed) investments. Our model and empirical
      results could partly explain the decline in the number of risky new molecular
      entities.

PMID- 28449354
TI  - Prevalence of, and work-related risk factors for, hand eczema in a Norwegian
      general population (The HUNT Study).
AB  - BACKGROUND: Chemical exposures at work and at home may cause hand eczema.
      However, this has been scarcely described for Norway. OBJECTIVES: To investigate
      the prevalence of, and occupational risk factors for, hand eczema in Norway.
      METHODS: Among 50 805 respondents (aged >=20 years) to the third Nord-Trondelag
      Health Study (HUNT3), 5757 persons reported ever having hand eczema, and 4206
      answered a hand eczema questionnaire. RESULTS: The lifetime prevalences of hand
      eczema were 8.4% in men and 13.8% in women (p < 0.001), with onset at age <=10
      years in 24% (men) and 20% (women), and onset at age >=30 years in 37% (men) and
      25% (women) (p < 0.001). Work-related hand eczema affected 4.8% of the
      population, and was most frequently associated with health/social work (29%) and
      occupational cleaning (20%) in women, and with farming (26%) and industrial
      occupations (27%) in men. Cleaning detergents (75%) and other chemicals (36%)
      were the most common exacerbating factors. CONCLUSIONS: The prevalence of hand
      eczema was 11.3%, and that of work-related hand eczema was 4.8%. Hand eczema was
      more common in women than in men, but with a later onset in men. Cleaning
      detergents were the most common aggravating factors. A large proportion of the
      Nord-Trondelag population is employed in farming, providing the possibility to
      identify farming as an important risk factor for hand eczema.

PMID- 28449355
TI  - FATHER-CHILD INTERACTIONS AT 3 MONTHS AND 24 MONTHS: CONTRIBUTIONS TO CHILDREN'S
      COGNITIVE DEVELOPMENT AT 24 MONTHS.
AB  - The quality of father-child interactions has become a focus of increasing
      research in the field of child development. We examined the potential
      contribution of father-child interactions at both 3 months and 24 months to
      children's cognitive development at 24 months. Observational measures of father
      child interactions at 3 and 24 months were used to assess the quality of fathers'
      parenting (n = 192). At 24 months, the Mental Developmental Index (MDI) of the
      Bayley Scales of Infant Development, Second Edition (N. Bayley, ) measured
      cognitive functioning. The association between interactions and cognitive
      development was examined using multiple linear regression analyses, adjusting for
      paternal age, education and depression, infant age, and maternal sensitivity.
      Children whose fathers displayed more withdrawn and depressive behaviors in
      father-infant interactions at 3 months scored lower on the MDI at 24 months. At
      24 months, children whose fathers were more engaged and sensitive as well as
      those whose fathers were less controlling in their interactions scored higher on
      the MDI. These findings were independent of the effects of maternal sensitivity.
      Results indicate that father-child interactions, even from a very young age
      (i.e., 3 months) may influence children's cognitive development. They highlight
      the potential significance of interventions to promote positive parenting by
      fathers and policies that encourage fathers to spend more time with their young
      children.

PMID- 28449356
TI  - Fetal head circumference and subpubic angle are independent risk factors for
      unplanned cesarean and operative delivery.
AB  - INTRODUCTION: The aim of this study was to ascertain whether combined ultrasound
      assessment of fetal head circumference (HC) and maternal subpubic angle (SPA)
      prior to the onset of labor may predict the likelihood of an unplanned operative
      delivery (UOD) in nulliparous women at term. MATERIAL AND METHODS: Prospective
      cohort study of singleton pregnancies in cephalic presentation. Pregnancies
      experiencing UOD secondary to fetal distress were excluded. HC was assessed
      transabdominally and SPA values were obtained from a reconstructed coronal plane
      on three-dimensional (3D) ultrasound performed translabially at 36-38 weeks of
      gestation. Maternal characteristics, HC expressed as multiple of median, and SPA
      were compared according to the mode of delivery. Logistic regression and receiver
      operating characteristics curve analyses were used to analyze the data. RESULTS:
      597 pregnancies were included in the study. Spontaneous vaginal delivery occurred
      in 70.2% of the cases and UOD was required in 29.8%. There was no difference in
      pregnancy characteristics and birthweight between women who had a spontaneous
      vaginal birth compared with UOD. The HC multiple of median was larger (1.00 +/-
      0.02 vs. 1.03 +/- 0.02, p <= 0.0001), whereas SPA was narrower in the UOD group
      (124.02 +/- 13.64 vs. 102.61 +/- 16.13, p <= 0.0001). At logistic regression, SPA
      (OR 0.91, 95% CI 0.89-0.93), HC multiple of median (OR 1.13, 95% CI 1.09-1.17)
      and maternal height (OR 0.95, 95% CI 0.92-0.99) were independently associated
      with UOD. When combined, the diagnostic accuracy of a predictive model
      integrating HC, SPA and maternal height was highly predictive of UOD with an area
      under the curve of 0.904 (95% CI 0.88-0.93). CONCLUSIONS: Ultrasound assessment
      of fetal HC and maternal SPA after 36 weeks of gestation can identify a subset of
      women at higher risk of UOD during labor, for whom early planned delivery might
      be beneficial.

PMID- 28449357
TI  - Premastication and length for age among children under 24 months in Laos.
AB  - Premastication of infant food by caregivers is common in Laos. Premastication is
      hypothesized to have both positive and negative implications for children, but
      the net effect of premastication on child health and nutrition is largely unknown
      because of a lack of research. This study quantitatively describes premastication
      in 5 provinces of Laos and examines the associations between premastication and
      the length of young children. We analyzed cross-sectional data from the Laos 2015
      Food and Nutrition Security Survey to characterize premastication among children
      under 2 years of age (n = 1,661) and to test associations between premastication
      and child length-for-age z-score. We explored associations using multilevel mixed
      effects linear regression. Among children 0-23 months, 27.2% of mothers reported
      giving premasticated food in the past week. Receipt of premasticated food was
      inversely associated with length-for-age z-score after controlling for potential
      confounders (child's age, ethno-linguistic group, wealth, and parity) among
      children 6-13 months (beta -0.36, CI [-0.68, -0.04]) and among children 14-23
      months (beta -0.43, CI [-0.81, -0.05]). For breastfed children 0-5 months who
      received complementary food, the coefficient was similar, but the association was
      not statistically significant (beta -0.42, CI [-1.2, 0.37]). Premastication is a
      common feeding practice for children 0-23 months of age, and many infants consume
      premasticated food on a daily basis. There was a negative relationship between
      premastication and child length. However, given the cross-sectional nature of
      this study and potential unmeasured confounding factors, reverse causality or
      confounding cannot be ruled out. Longitudinal studies are needed to develop
      recommendations on premastication.

PMID- 28449358
TI  - Incident rate and risk factors for tuberculosis among patients with type 2
      diabetes: retrospective cohort study in Shanghai, China.
AB  - OBJECTIVE: To examine the incident rate of tuberculosis (TB) and its associates
      among adults with type 2 diabetes in Shanghai, China. METHODS: We conducted a
      retrospective cohort study among 170 399 patients with type 2 diabetes aged >=18
      years who were registered in Shanghai community-based diabetes management system
      between 2004 and 2009. Their TB status was tracked until 31 December 2014. Cox
      regression was performed to identify the risk factors for TB. RESULTS: We
      documented 785 new TB cases during 654 977 person-years of follow-up. The
      incident rate of TB was 224.20 (206.69, 243.16) per 100 000 person-years among
      men and 51.34 (44.75, 58.92) per 100 000 person-years among women. A 1-unit
      increase of BMI was associated with a risk reduction in 16% (P < 0.01) for men
      and a 14% (P < 0.01) reduction for women. TB cases were more likely to be insulin
      dependent [men: hazard ratio = 2.13 (1.29, 3.53); women: 3.28 (1.28, 8.39)] and
      had a poor glucose level initially [men: 1.21 (1.15, 1.27); women: 1.27 (1.18,
      1.37)]. The risk factor for TB specific to men was a young age at diagnosis of
      diabetes, and the protective factor specific to women was actively engaging in
      physical activity. CONCLUSIONS: TB incident rate among patients with type 2
      diabetes was substantially higher among men than among women. The risk of TB was
      reversely associated with initial BMI. The severity of poor glucose control among
      patients with diabetes was also linearly associated with the risk of TB.

PMID- 28449359
TI  - Transcriptomic responses of Solanum dulcamara to natural and simulated herbivory.
AB  - Plants are attacked by diverse herbivores and respond with manifold defence
      responses. To study transcriptional and other early regulation events of these
      plant responses, herbivory is often simulated to standardize the temporal and
      spatial dynamics that vary tremendously for natural herbivory. Yet, to what
      extent such simulations of herbivory are able to elicit the same plant response
      as real herbivory remains largely undetermined. We examined the transcriptional
      response of a wild model plant to herbivory by lepidopteran larvae and to a
      commonly used herbivory simulation by applying the larvae's oral secretions to
      standardized wounds. We designed a microarray for Solanum dulcamara and showed
      that the transcriptional responses to real and to simulated herbivory by
      Spodoptera exigua overlapped moderately by about 40%. Interestingly, certain
      responses were mimicked better than others; 60% of the genes upregulated but not
      even a quarter of the genes downregulated by herbivory were similarly affected by
      application of oral secretions to wounds. While the regulation of genes involved
      in signalling, defence and water stress was mimicked well by the simulated
      herbivory, most of the genes related to photosynthesis, carbohydrate- and lipid
      metabolism were exclusively regulated by real herbivory. Thus, wounding and
      application of oral secretions decently mimics herbivory-induced defence
      responses but likely not the reallocation of primary metabolites induced by real
      herbivory.

PMID- 28449360
TI  - Biologic variability of cardiac troponin I in healthy dogs and dogs with
      different stages of myxomatous mitral valve disease using standard and high
      sensitivity immunoassays.
AB  - BACKGROUND: Biologic variability (BV) is one aspect of interpreting changes in
      biomarker concentrations known to be clinically important in people with cardiac
      disease, but it has not been adequately addressed in dogs so far. OBJECTIVES: The
      purpose of the study was to determine BV of cardiac troponin I (cTnI) in healthy
      dogs and dogs with 3 stages of myxomatous mitral valve disease (MMVD). METHODS:
      Healthy dogs and dogs with 3 stages of MMVD were prospectively assigned to groups
      based on comprehensive clinical evaluation using current guidelines.
      Concentrations of cTnI were measured hourly, daily, and weekly using standard and
      high-sensitivity immunoassays. Within- (CVI ) and between-subject (CVG )
      coefficients of variability, percent reference change value (RCV), and index of
      individuality (IoI) were calculated. RESULTS: All 10 healthy dogs and 76/112
      (68%) of samples from 28 MMVD dogs had cTnI concentrations below the limit of
      detection (LOD) using a standard sensitivity immunoassay. Only 49/160 (31%) of
      healthy dog samples and no MMVD samples had cTnI below the high-sensitivity
      immunoassay LOD. Data analysis for the high-sensitivity immunoassay revealed CVI
      of 48.1%, CVG of 60.1%, RCV of 134.0%, and IoI of 0.804 in healthy dogs. In MMVD
      dogs, CVI was 39.6%, CVG was 80.7%, RCV was 110%, and IoI was 0.494. Of all MMVD
      dogs, those with Stage B2 had the lowest RCV of 91%. CONCLUSIONS: Biologic
      variability affects cTnI concentrations in healthy dogs and dogs with MMVD.
      Consideration of BV may be clinically relevant when monitoring individual changes
      in cTnI values, using high-sensitivity immunoassays.

PMID- 28449361
TI  - Systematic review with meta-analysis: proximal disease extension in limited
      ulcerative colitis.
AB  - BACKGROUND: Disease extent in ulcerative colitis is one of the major factors
      determining prognosis over the long-term. Disease extent is dynamic and a
      proportion of patients presenting with limited disease progress to more extensive
      forms of disease over time. AIM: To perform a systematic review and meta-analysis
      of epidemiological studies reporting on extension of ulcerative colitis to
      determine frequency of disease extension in patients with limited ulcerative
      colitis at diagnosis. METHODS: We performed a systematic literature search to
      identify studies on disease extension of ulcerative colitis (UC) and predictors
      of disease progression. RESULTS: Overall, 41 studies were eligible for systematic
      review but only 30 for meta-analysis. The overall pooled frequency of UC
      extension was 22.8% with colonic extension being 17.8% at 5 years and 31% at 10
      years. Extension was 17.8% (95% CI 11.2-27.3) from E1 to E3, 27.5% (95% CI 7.6
      45.6) from E2 to E3 and 20.8% (95% CI 11.4-26.8) from E1 to E2. Rate of extension
      was significantly higher in patients younger than 18 years (29.2% (CI 6.4-71.3)
      compared to older patients (20.2% (CI 13.0-30.1) (P<.0001). Risk of extension was
      significantly higher in patients from North America (37.8%) than from Europe
      (19.6%) (P<.0001). CONCLUSIONS: In this meta-analysis, approximately one quarter
      of patients with limited UC extend over time with most extension occurring during
      the first 10 years. Rate of extension depends on age at diagnosis and geographic
      origin. Predicting those at high risk of disease extension from diagnosis could
      lead to personalised therapeutic strategies.

PMID- 28449362
TI  - Duration and exclusiveness of breastfeeding and risk of childhood atopic
      diseases.
AB  - BACKGROUND: Breastfeeding may have immune modulatory effects that influence the
      development of childhood allergic sensitization and atopic diseases. We aimed to
      examine the associations of breastfeeding with childhood allergic sensitization,
      inhalant or food allergy and eczema, and whether any association was affected by
      disease-related modification of the exposure or modified by maternal history of
      allergy, eczema, or asthma. METHODS: This study among 5828 children was performed
      in a population-based prospective cohort from fetal life onwards. We collected
      information on duration (<2 months, 2-4 months, 4-6 months, and >=6 months) and
      exclusiveness (nonexclusive vs exclusive for 4 months) of breastfeeding in
      infancy by postal questionnaires. At age 10 years, inhalant allergic
      sensitization and food-allergic sensitization were measured by skin prick tests,
      and physician-diagnosed inhalant and food allergy by a postal questionnaire. Data
      on parental-reported eczema were available from birth until age 10 years.
      RESULTS: We observed no association of breastfeeding with any allergic
      sensitization, physician-diagnosed allergy, or combination of these outcomes.
      Shorter breastfeeding duration was associated with an overall increased risk of
      eczema (P-value for trend <.05). Nonexclusively breastfed children had an overall
      increased risk of eczema (adjusted odds ratio [95% confidence interval]: 1.11
      [1.01, 1.23]), compared with children exclusively breastfed for 4 months. Risk
      period-specific sensitivity analyses, additional adjustment for ointment use for
      eczema at age 2 months, and cross-lagged modeling showed no consistent results
      for disease-related modification of the exposure. Results were not modified by
      maternal history of allergy, eczema, or asthma (lowest P-value for
      interaction=.13). CONCLUSION: Shorter duration or nonexclusiveness of
      breastfeeding is associated with a weak overall increased risk of eczema but not
      allergic sensitization or physician-diagnosed allergy at age 10 years.

PMID- 28449363
TI  - Health literacy interventions for immigrant populations: a systematic review.
AB  - BACKGROUND: Health literacy is considered a social health determinant that
      influences improvement in health, patient empowerment and reduction in
      inequalities. There is a lack of health literacy interventions for vulnerable
      social groups (i.e. immigrants), and nurses have shown little familiarity with
      the concept. AIM: This study aimed to identify and analyse whether interventions
      directed at immigrant populations improve the functional (basic reading, writing
      and arithmetic skills), interactive (social and cognitive skills) and critical
      (advanced cognitive and social skills in critically analyzing information and
      making informed decisions) dimensions of health literacy, taking into account the
      role played by nursing in these interventions. METHODS: A systematic review of
      four databases including PubMed, PsycINFO, the Cochrane Library and ERIC was
      conducted to identify relevant articles published between 2000 and 2015. Thirty
      four articles met the inclusion criteria, and nine articles used a validated
      instrument. RESULTS: Few specific health literacy interventions for immigrant
      populations were found. The main findings of the studies showed positive changes
      in functional health literacy. However, the interventions were less effective in
      improving interactive and critical health literacy. LIMITATIONS: Several of the
      findings of this review were based on studies that had their own limitations. The
      assessment of the articles was not blinded, and the review was restricted to
      articles written in Spanish and English. CONCLUSIONS: The interventions studied
      were reported as being effective in improving health literacy in immigrants,
      particularly the functional aspects. Regarding the role played by nursing, this
      review observed little involvement. IMPLICATIONS FOR NURSING AND HEALTH POLICY:
      It is important for educational strategies to include health literacy dimensions.
      The concept of health literacy should be included as a Nursing Outcomes
      Classification and in its subsequent validation taxonomy. To promote community
      health, health literacy must be a prioritized objective of health management and
      policies.

PMID- 28449364
TI  - The Association Between Peritraumatic Dissociation and PTSD Symptoms: The
      Mediating Role of Negative Beliefs About the Self.
AB  - Peritraumatic dissociation, a term used to describe a complex array of reactions
      to trauma, including depersonalization, derealization, and emotional numbness,
      has been associated with posttraumatic stress disorder (PTSD) symptoms across a
      number of studies. Cognitive theory suggests that interpretations of traumatic
      events and reactions underlie the persistence of PTSD. The present study examined
      the associations among peritraumatic dissociation, posttraumatic cognitions, and
      PTSD symptoms in a group of trauma-exposed adults (N = 169). Results indicated
      that, after accounting for overall symptom severity and current dissociative
      tendencies, peritraumatic dissociation was significantly predictive of negative
      beliefs about the self (R2 = .06, p < .001). Other categories of maladaptive
      posttraumatic cognitions did not show a similar relationship (R2 = .01 to .02,
      nonsignificant). Negative thoughts about the self partially mediated the
      association between peritraumatic dissociation and PTSD severity (completely
      standardized indirect effect = .25). These findings lend support to cognitive
      theories of PTSD and point to an important area for clinical intervention.

PMID- 28449365
TI  - Duty-Related Trauma Exposure and Posttraumatic Stress Symptoms in Professional
      Firefighters.
AB  - Firefighters commonly encounter traumatic events during duty hours. The purpose
      of this study was to investigate the characteristics of duty-related trauma as
      risk factors for posttraumatic stress disorder in professional firefighters. A
      sample of 212 firefighters participated in the study and completed self-reported
      questionnaires. Potentially traumatic events (PTE) were assessed using a list of
      17 traumatic event types. The posttraumatic stress symptoms (PTSS) were measured
      by the Impact of Event Scale-Revised (Lim et al., 2009; Weiss, 2007). A higher
      score for the composite index, which reflects both multiple PTE and peritraumatic
      suffering, increased the odds for significant PTSS after adjusting for age, sex,
      marital status, education, numbers of years worked, childhood trauma, and
      depressive symptoms (adjusted odds ratio [AOR] = 2.26, p = .001, Cohen's d =
      0.20). Furthermore, indirect (AOR = 1.93, p = .009, Cohen's d = .16) and
      colleague-related PTE (AOR = 1.97, p = .037, Cohen's d = .16) showed significant
      associations with PTSS. It is noteworthy that the combination of multiple PTE and
      peritraumatic suffering was more predictive of PTSS than either factor alone. Our
      findings also suggest that daily work exposure to indirect PTE may contribute to
      the occurrence of PTSS among professional firefighters.

PMID- 28449366
TI  - Moving forward with the neuromuscular junction.
AB  - The neuromuscular junction (NMJ) is indispensable for survival. This synapse
      between motoneurons and skeletal muscle fibers allows posture, movement and
      respiration. Therefore, its dysfunction creates pathologies than can be lethal.
      The molecular mechanisms of NMJ development and maintenance are the subject of
      intensive studies. This mini-review focuses on some of the most recent
      discoveries. An unexpected role for a protein, rapsyn, which has been known for
      40 years to aggregate acetylcholine receptors has emerged. A new cell partner at
      NMJ has been unmasked and is challenging our understanding of the functioning of
      this synapse. Toxins are now used as new tools to study
      degeneration/regeneration. The possibility of creating human NMJ in vitro is
      within reach with major consequences for drug screening. Wnts are secreted
      neurogenic factors that have been involved in vitro in acetylcholine receptor
      clustering, but their precise role in vivo remains to be clarified. All these
      data are raising new and exciting perspectives in the field and are discussed in
      this Review. This is an article for the special issue XVth International
      Symposium on Cholinergic Mechanisms.

PMID- 28449367
TI  - Metoprolol-pridopidine drug-drug interaction and food effect assessments of
      pridopidine, a new drug for treatment of Huntington's disease.
AB  - AIMS: Pridopidine is an oral drug in clinical development for treatment of
      patients with Huntington's disease. This study examined the interactions of
      pridopidine with in vitro cytochrome P450 activity and characterized the effects
      of pridopidine on CYP2D6 activity in healthy volunteers using metoprolol as a
      probe substrate. The effect of food on pridopidine exposure was assessed.
      METHODS: The ability of pridopidine to inhibit and/or induce in vitro activity of
      drug metabolizing enzymes was examined in human liver microsomes and fresh
      hepatocytes. CYP2D6 inhibition potency and reversibility was assessed using
      dextromethorphan. For the clinical assessment, 22 healthy subjects were given
      metoprolol 100 mg alone and concomitantly with steady-state pridopidine 45 mg
      twice daily. Food effect on a single 90 mg dose of pridopidine was evaluated in a
      crossover manner. Safety assessments and pharmacokinetic sampling occurred
      throughout the study. RESULTS: Pridopidine was found to be a metabolism dependent
      inhibitor of CYP2D6, the main enzyme catalysing its own metabolism. Flavin
      containing monooxygenase heat inactivation of liver microsomes did not affect
      pridopidine metabolism-dependent inhibition of CYP2D6 and its inhibition of
      CYP2D6 was not reversible with addition of FeCN3 . Exposure to metoprolol was
      markedly increased when coadministered with pridopidine; the ratio of the
      geometric means (90% confidence interval) for maximum observed plasma
      concentration, and area under the plasma concentration-time curve from time 0 to
      the time of the last quantifiable concentration and extrapolated to infinity were
      3.5 (2.9, 4.22), 6.64 (5.27, 8.38) and 6.55 (5.18, 8.28), respectively. Systemic
      exposure to pridopidine was unaffected by food conditions. CONCLUSIONS: As
      pridopidine is a metabolism-dependent inhibitor of CYP2D6, systemic levels of
      drugs metabolized by CYP2D6 may increase with chronic coadministration of
      pridopidine. Pridopidine can be administered without regard to food.

PMID- 28449368
TI  - A randomized, placebo- and sitagliptin-controlled trial of the safety and
      efficacy of omarigliptin, a once-weekly dipeptidyl peptidase-4 inhibitor, in
      Japanese patients with type 2 diabetes.
AB  - AIMS: To assess the safety and efficacy of omarigliptin in Japanese patients with
      type 2 diabetes (T2D). METHODS: In a 24-week double-blind trial, 414 patients
      with T2D were randomized to omarigliptin 25 mg once weekly, sitagliptin 50 mg
      once daily or placebo. The double-blind period was followed by a 28-week open
      label extension during which all patients received omarigliptin 25 mg once
      weekly. Efficacy endpoints were glycated haemoglobin (HbA1c), 2-hour postprandial
      glucose (PPG) and fasting plasma glucose (FPG) levels. RESULTS: After 24 weeks,
      the least squares (LS) mean change from baseline in HbA1c was -0.66% for
      omarigliptin, -0.65% for sitagliptin and 0.13% for placebo. The difference in LS
      mean for omarigliptin vs placebo was -0.80% ( P  < .001). The difference in LS
      mean for omarigliptin vs sitagliptin was -0.02% (95% confidence interval -0.15,
      0.12), which met the criterion for non-inferiority to sitagliptin. Both active
      treatments provided significant reductions in FPG and 2-hour PPG compared with
      placebo (P < .001). Over the 24-week double-blind period, there were no
      clinically meaningful differences in the incidence rates of adverse events among
      the treatment groups. There was 1 episode of symptomatic hypoglycaemia in the
      sitagliptin group and none in the omarigliptin or placebo groups. In the 28-week
      open-label period, omarigliptin provided persistent improvements in glycaemic
      control without notable change in safety profile compared with the double-blind
      period. Omarigliptin had no meaningful effect on body weight. CONCLUSIONS: In
      Japanese patients with T2D, omarigliptin 25 mg once weekly provided significant
      glucose-lowering compared with placebo and was non-inferior to sitagliptin 50 mg
      once daily. Omarigliptin was generally well tolerated for up to 52 weeks.

PMID- 28449370
TI  - The burden of autoimmunity in myelodysplastic syndromes.
AB  - The clinical history of patients with myelodysplastic syndromes (MDS) is
      characterised by bone marrow insufficiency as well as by the possible evolution
      into acute leukaemia. However a number of reports highlight the frequent
      occurrence of autoimmune manifestations involving different sites and organs. The
      present review will first describe the clinical pictures most often observed in
      MDS patients. The actual burden of autoimmunity will be then addressed by
      focusing on the few available registry studies. Finally, the potential collateral
      impact of specific treatments for MDS on the evolution of autoimmune disorders
      will be considered.

PMID- 28449371
TI  - Relationship between cytotoxic T-lymphocyte antigen 4 -318C/T (rs5742909) gene
      polymorphism and the risk of acute rejection in renal transplantation.
AB  - Results on the relationship between CTLA4 -318C/T (rs5742909) gene polymorphism
      and risk of acute rejection in renal transplantation are still conflicting. This
      meta-analysis was performed to update the association between CTLA4 -318C/T and
      risk of acute rejection in renal transplantation. The association investigations
      were identified from PubMed and Cochrane Library, and eligible studies were
      included and synthesized using meta-analysis method. Twelve reports were included
      in this meta-analysis for the association of CTLA4 -318C/T gene polymorphism with
      acute rejection risk in renal transplantation, consisting of 728 acute rejection
      patients and 1628 non-acute rejection controls. The association between CTLA4 
      318C/T gene polymorphism and acute rejection risk in renal transplantation for
      overall populations was not found in this meta-analysis (T allele: OR=0.96, 95%
      CI: 0.60-1.54, P=.88; TT genotype: OR=0.90, 95% CI: 0.47-1.71, P=.74; CC
      genotype: OR=1.00, 95% CI: 0.62-1.59, P=.98). Interestingly, T allele was
      associated with the risk of acute rejection in renal transplantation in African
      population. In conclusion, CTLA4 -318C/T gene polymorphism is not associated with
      the risk of acute rejection in renal transplantation in overall populations.

PMID- 28449369
TI  - Exposure to the insecticide endosulfan induces liver morphology alterations and
      oxidative stress in fruit-eating bats (Artibeus lituratus).
AB  - Exposure to pesticides may increase the generation of reactive oxygen species
      (ROS), leading to oxidation of cell membrane lipids and proteins. Although fruit
      bats are potentially exposed to pesticides during their entire lifespan, the
      impacts of this exposure are still poorly investigated. We examined the effects
      of low, commercially recommended concentrations (0, 1.05 and 2.1 g/l) of an
      organochlorine insecticide endosulfan (EDS) formulation on oxidative responses in
      the liver and kidneys of Neotropical fruit bats (Artibeus lituratus), as well as
      possible liver morphological alterations following a 35-day oral exposure.
      Superoxide dismutase activity was significantly decreased upon exposure to 1.05
      g/l of EDS in the liver and kidneys, catalase was decreased in the liver of 2.1
      g/l EDS-exposed bats, while glutathione S-transferase was increased in the liver
      of 2.1 g/l EDS-exposed bats. Protein carbonyls increased following the exposure
      to the highest EDS dose tested. Endosulfan-induced morphological alterations in
      the liver included cell degeneration and cell death, with apparent cytoplasm
      lipid accumulation (steatosis) and pyknotic nuclei, karyolysis and deposit of
      collagen fibres. Our findings suggest that exposure to low concentrations of EDS
      induced a certain extent of oxidative damage in fruit bats, which may have led to
      liver morphological alterations.

PMID- 28449372
TI  - The impact of mood on empathy for pain: Evidence from an EEG study.
AB  - The current work investigated whether the neural correlates of empathy for pain
      are altered by mood valence of observers. Following mood induction, participants
      watched pictures representing painful or nonpainful situations. We used EEG to
      record neural activity and assessed event-related desynchronization at central
      sites during pain observation. Greater mu desynchronization was observed during
      painful relative to nonpainful situations in positive and neutral mood but not in
      negative mood. We also found that the pain empathy effect, indexed by mu
      suppression differences between painful and nonpainful conditions, was smaller in
      negative than in neutral and positive mood, while this effect was similar between
      neutral and positive mood. The current study demonstrates that observers' mood
      states influence the motoric component of empathy for pain, and specifically the
      negative mood suppresses the motoric empathic resonance for others' pain.

PMID- 28449373
TI  - Biophysical analysis of the dynamics of calmodulin interactions with neurogranin
      and Ca2+ /calmodulin-dependent kinase II.
AB  - Calmodulin (CaM) functions depend on interactions with CaM-binding proteins,
      regulated by Ca2+. Induced structural changes influence the affinity, kinetics,
      and specificities of the interactions. The dynamics of CaM interactions with
      neurogranin (Ng) and the CaM-binding region of Ca2+/calmodulin-dependent kinase
      II (CaMKII290-309 ) have been studied using biophysical methods. These proteins
      have opposite Ca2+ dependencies for CaM binding. Surface plasmon resonance
      biosensor analysis confirmed that Ca2+ and CaM interact very rapidly, and with
      moderate affinity ( KDSPR=3MUM). Calmodulin-CaMKII290-309 interactions were only
      detected in the presence of Ca2+, exhibiting fast kinetics and nanomolar affinity
      ( KDSPR=7.1nM). The CaM-Ng interaction had higher affinity under Ca2+-depleted (
      KDSPR=480nM,k1=3.4*105M-1s-1 and k-1 = 1.6 * 10-1 s-1 ) than Ca2+-saturated
      conditions ( KDSPR=19MUM). The IQ motif of Ng (Ng27-50 ) had similar affinity for
      CaM as Ng under Ca2+-saturated conditions ( KDSPR=14MUM), but no interaction was
      seen under Ca2+-depleted conditions. Microscale thermophoresis using
      fluorescently labeled CaM confirmed the surface plasmon resonance results
      qualitatively, but estimated lower affinities for the Ng ( KDMST=890nM) and
      CaMKII290-309 ( KDMST=190nM) interactions. Although CaMKII290-309 showed expected
      interaction characteristics, they may be different for full-length CaMKII. The
      data for full-length Ng, but not Ng27-50 , agree with the current model on Ng
      regulation of Ca2+/CaM signaling.

PMID- 28449374
TI  - Genetic Variability in Adenosine Deaminase-Like Contributes to Variation in
      Alcohol Preference in Mice.
AB  - BACKGROUND: A substantial part of the risk for alcohol use disorder is determined
      by genetic factors. We previously used chromosome substitution (CSS) mice, to
      identify a quantitative trait loci (QTL) for alcohol preference on mouse
      chromosome 2. The aim of this study was to identify candidate genes within this
      QTL that confer the risk for alcohol preference. METHODS: In order to delineate
      the neurobiological underpinnings of alcohol consumption, we expanded on the QTL
      approach to identify candidate genes for high alcohol preference in mice. We
      narrowed down a QTL for alcohol preference on mouse chromosome 2, that we
      previously identified using CSS mice, to 4 candidate genes in silico. Expression
      levels of these candidate genes in prefrontal cortex, amygdala, and nucleus
      accumbens-brain regions implicated in reward and addiction-were subsequently
      compared for the CSS-2 and the C57BL/6J host strain. RESULTS: We observed
      increased expression of adenosine deaminase-like (Adal) in all 3 regions in CSS-2
      mice. Moreover, we found that the adenosine deaminase inhibitor EHNA reduced the
      difference in alcohol preference between CSS-2 and C57BL/6J mice. CONCLUSIONS:
      This study identifies Adal as a genetically protective factor against alcohol
      consumption in mice, in which elevated Adal levels contribute to low alcohol
      preference.

PMID- 28449375
TI  - The genetic dimension of pest pressure in the tropical rainforest.
AB  - Wet tropical forests are among the most diverse ecosystems on Earth and can host
      several hundreds of tree species per hectare. To maintain such diversity, the
      community must contain large numbers of relatively rare species rather than be
      dominated by a few very common trees, as is often the case in temperate forests.
      Explaining the mechanisms preventing dominance by common species has been a major
      task of tropical forest ecology. One of the most promising mechanisms is negative
      density dependence (NDD) of tree abundance driven by pests, including fungal
      diseases ('pest pressure'). NDD entails that the chance of survival of a sapling
      increases with the distance from a mature tree of the same species, thus
      preventing species from becoming locally dominant. Curiously, the strength of NDD
      is negatively correlated with abundance, meaning that tree species that are more
      common generally show weaker NDD (Comita et al. ). Interactions between plants
      and soil pathogens have been shown to play an important role in NDD (Klironomos
      ), and rare species are apparently more strongly affected (Mangan et al. ).
      However, the genetic mechanisms underlying this phenomenon have remained obscure.
      In this issue of Molecular Ecology, Marden et al. () suggest that reduced
      diversity of the genes involved in pathogen recognition (Resistance genes or R
      genes) could explain why NDD is stronger in locally rare species.

PMID- 28449376
TI  - Psychological Distress and Widespread Pain Contribute to the Variance of the
      Central Sensitization Inventory: A Cross-Sectional Study in Patients with Chronic
      Pain.
AB  - OBJECTIVES: Central sensitization (CS) implies increased sensitivity of the
      nervous system, resulting in increased pain sensitivity as well as widespread
      pain. Recently, the Central Sensitization Inventory (CSI) was developed to assess
      symptoms of CS and central sensitivity syndromes. The aim of this study was to
      examine the convergent validity of the CSI by comparing the outcome to
      psychosocial factors and clinical features of CS. METHODS: In a cross-sectional
      explorative study, patients with chronic pain completed multiple questionnaires,
      including the CSI, Pain Catastrophizing Scale, and Symptom Checklist 90, for
      psychological distress, duration of pain, intensity of pain, widespread pain, and
      lateralization of pain. Based on bivariate correlations, relevant predictors of
      CS were selected and used to fit an exploratory structural equation model (SEM)
      of CS. RESULTS: In total, 114 patients with chronic pain were included, 56.1%
      being women. The average pain duration was 88 months. The mean total score on the
      CSI was 36.09 (15.26). The CSI was strongly related to known contributing and
      related factors of CS. SEM analysis showed that both psychological distress and
      widespread pain contributed significantly to the variance in symptoms of CS in
      patients with chronic pain. CONCLUSION: In this study, the convergent validity of
      the CSI was measured with demonstration of a strong relationship between
      contributing factors and clinical features of CS. These findings of convergent
      validity, considering former studies of the CSI, underline the use of the
      questionnaire in the clinical practice.

PMID- 28449377
TI  - Topical antiviral and antifungal medications in pregnancy: a review of safety
      profiles.
AB  - Medications should be employed with caution in women of childbearing age who are
      pregnant or considering pregnancy. Compared to oral or parenteral agents, topical
      medications have limited systemic absorption and are deemed safer. However, their
      safety profile must be assessed cautiously due to the limited available data. In
      this article, we aggregate human and animal studies to provide recommendations on
      utilizing topical antiviral and antifungal medications in pregnancy. For
      antiviral medications, acyclovir and trichloroacetic acid are safe to use in
      pregnancy. Docosanol, imiquimod and penciclovir are likely safe, but should be
      utilized as second-line agents. Podofilox and podophyllin resin should be
      avoided. For antifungal medications, clotrimazole, miconazole and nystatin are
      considered first-line agents. Butenafine, ciclopirox, naftifine, oxiconazole and
      terbinafine may be utilized after the above agents. Econazole should be avoided
      during the first trimester and used sparingly during 2nd and 3rd trimester.
      Ketoconazole and selenium sulphide are likely safe, but should be employed in
      limited areas for brief periods.

PMID- 28449378
TI  - Analysis of toldimfos in porcine muscle and bovine milk using liquid
      chromatography-triple quadrupole mass spectrometry.
AB  - An analytical method was developed for the detection of toldimfos sodium residues
      in porcine muscle and bovine milk using liquid chromatography-triple quadrupole
      tandem mass spectrometry (LC-MS/MS) analysis. The drug was extracted from muscle
      and milk using 10 mm ammonium formate in acetonitrile and then purified using n
      hexane. The drug was well separated on a Luna C18 column using a mixture of 10 mm
      ammonium formate in ultrapure water (A) and acetonitrile (B) as the mobile phase.
      Good linearity was achieved over the tested concentration range (0.005-0.03
      mg/kg) in matrix-matched standard calibration. The determination coefficients (R2
      ) were 0.9942 and 0.9898 for muscle and milk, respectively. Fortified porcine
      muscle and bovine milk contained concentrations equivalent to and twice the limit
      of quantification (0.005 mg/kg) yielded recoveries in the range of 75.58-89.74%
      and relative standard deviations of <=8.87%. Samples collected from large markets
      located in Seoul, Republic of Korea, tested negative for toldimfos sodium
      residue. In conclusion, ammonium formate in acetonitrile can effectively extract
      toldimfos sodium from porcine muscle and bovine milk without solid-phase
      extraction, which is usually required for cleanup before analysis. This method
      can be applied for the routine analysis of toldimfos in foods of animal origins.

PMID- 28449379
TI  - Naloxone rescheduling in Australia: Processes, implementation and challenges with
      supply of naloxone as a 'pharmacist only' over-the-counter medicine.
AB  - ISSUES: Numerous studies and systematic reviews have concluded that naloxone for
      take-home use is an effective intervention to reduce overdose morbidity and
      mortality, with few side effects and no abuse potential. One barrier to supply is
      that naloxone has traditionally been a prescription medication. In May 2015, the
      Therapeutic Goods Administration of Australia announced the intention to down
      schedule naloxone when used for the treatment of opioid overdose, enabling sale
      in pharmacies without a prescription. The aim of this article is to describe
      process of rescheduling of naloxone and some of the challenges observed.
      APPROACH: We describe the process of rescheduling from initial proposal
      development to gaining support and submissions from a range of individuals and
      professional bodies to support this change. The implications of the change,
      particularly for pharmacy supply of naloxone, are discussed, including next steps
      to facilitate implementation of this change in the Australian context. KEY
      FINDINGS: A submission to reschedule naloxone was successfully instigated by a
      member of the public. The change may help remove access barriers to naloxone by
      allowing pharmacist supply. Cost, pharmacist training, existing naloxone
      formulation, presentation and packaging remain challenges to address.
      IMPLICATIONS AND CONCLUSION: Naloxone down-scheduling has opened up an additional
      way to supply naloxone through community pharmacy. Further expansion of naloxone
      availability may be achieved through addressing cost as a barrier, and making
      naloxone more widely accessible through needle syringe programs, and other
      services that do not have medical staff.

PMID- 28449381
TI  - Predicting the Solubility of Sulfur: A COSMO-RS-Based Approach to Investigate
      Electrolytes for Li-S Batteries.
AB  - Lithium-sulfur (Li-S) batteries are, in theory, considering their basic
      reactions, very promising from a specific energy density point of view, but have
      poor power rate capabilities. The dissolution of sulfur from the C/S cathode in
      the electrolyte is a rate-determining and crucial step for the functionality. To
      date, time-consuming experimental methods, such as HPLC/UV, have been used to
      quantify the corresponding solubilities. Here, we use a computational fluid-phase
      thermodynamics approach, the conductor-like screening model for real solvents
      (COSMO-RS), to compute the solubilities of sulfur in different binary and ternary
      electrolytes. By using both explicit and implicit solvation approaches for
      lithium bistrifluoromethanesulfonimidate (LiTFSI)-containing electrolytes, a
      deviation of <0.4 log units was achieved with respect to experimental data,
      within the range of experimental error, thus proving COSMO-RS to be a useful tool
      for exploring novel Li-S battery electrolytes.

PMID- 28449380
TI  - The PAS domains of the major sporulation kinase in Bacillus subtilis play a role
      in tetramer formation that is essential for the autokinase activity.
AB  - Sporulation in Bacillus subtilis is induced upon starvation. In a widely accepted
      model, an N-terminal "sensor" domain of the major sporulation kinase KinA
      recognizes a hypothetical starvation signal(s) and autophosphorylates a histidine
      residue to activate the master regulator Spo0A via a multicomponent phosphorelay.
      However, to date no confirmed signal has been found. Here, we demonstrated that
      PAS-A, the most N-terminal of the three PAS domains (PAS-ABC), is dispensable for
      the activity, contrary to a previous report. Our data indicated that the
      autokinase activity is dependent on the formation of a functional tetramer, which
      is mediated by, at least, PAS-B and PAS-C. Additionally, we ruled out the
      previously proposed notion that NAD+ /NADH ratio controls KinA activity through
      the PAS-A domain by demonstrating that the cofactors show no effects on the
      kinase activity in vitro. In support of these data, we found that the cofactors
      exist in approximately 1000-fold excess of KinA in the cell and the cofactors'
      ratio does not change significantly during growth and sporulation, suggesting
      that changes in the cofactor ratio might not play a role in controlling KinA
      activity. These data may refute the widely-held belief that the activity of KinA
      is regulated in response to an unknown starvation signal(s).

PMID- 28449382
TI  - Current use of chromosomal microarray by Australian paediatricians and
      implications for the implementation of next generation sequencing.
AB  - AIM: Chromosomal microarray (CMA) is an important diagnostic test for children
      with multiple congenital anomalies or certain developmental behavioural problems
      suggestive of an underlying genetic diagnosis. However, there are medical and
      ethical complexities to its use and few Australian policies to guide practice. We
      aimed to describe the current practice of Australian paediatricians in relation
      to CMA testing. We hypothesised that there are knowledge gaps in their use of
      CMA. METHODS: Online survey completed between September 2015 and January 2016 by
      paediatricians in secondary care settings. Participants were members of the
      Australian Paediatric Research Network. One hundred and sixty five (43%) of 383
      active members responded. Our main outcome measures comprised: (i) the
      indications for which paediatricians request CMA; (ii) their approach to consent;
      (iii) their interpretation of results; and (iv) their understanding of the impact
      on patient management. RESULTS: A significant proportion of paediatricians (21
      52%) did not regularly use CMA for conditions with established evidence of
      diagnostic yield. Paediatricians under-estimated the potential for CMA findings
      to alter patient management. There was wide variability in paediatricians'
      approach to consent, and low use of consent forms and fact sheets. Paediatricians
      reported difficulties interpreting CMA results, with high rates of referral to
      clinical genetics services. CONCLUSIONS: The reported practice of Australian
      paediatricians is not consistent with international standards on CMA. Australian
      practice could be improved by a standardised approach to ordering CMA, consenting
      patients and interpreting results. We provide resources for CMA ordering and make
      recommendations about preparation for next generation sequencing.

PMID- 28449384
TI  - Iron status, body size, and growth in the first 2 years of life.
AB  - Rapid growth in infancy has been shown to adversely affect iron status up to 1
      year; however the effect of growth on iron status in the second year of life has
      been largely unexplored. We aimed to investigate the impact of growth and body
      size in the first 2 years on iron status at 2 years. In the prospective, maternal
      infant Cork BASELINE Birth Cohort Study, infant weight and length were measured
      at birth, 2, 6, 12, and 24 months and absolute weight (kg) and length (cm) gain
      from 0 to 2, 0 to 6, 0 to 12, 6 to 12, 12 to 24, and 0 to 24 months were
      calculated. At 2 years (n = 704), haemoglobin, mean corpuscular volume, and serum
      ferritin (umbilical cord concentrations also) were measured. At 2 years, 5% had
      iron deficiency (ferritin < 12 MUg/L) and 1% had iron deficiency anaemia
      (haemoglobin < 110 g/L + ferritin < 12 MUg/L). Weight gain from 6 to 12, 0 to 24,
      and 12 to 24 months were all inversely associated with ferritin concentrations at
      2 years but only the association with weight gain from 12 to 24 months was robust
      after adjustment for potential confounders including cord ferritin (adj. estimate
      95% CI: -4.40 [-8.43, -0.37] MUg/L, p = .033). Length gain from 0 to 24 months
      was positively associated with haemoglobin at 2 years (0.42 [0.07, 0.76] g/L, p =
      .019), only prior to further adjustment for cord ferritin. To conclude, weight
      gain in the second year was inversely associated with iron stores at 2 years,
      even after accounting for iron status at birth. Further examinations of iron
      requirements, dietary intakes, and growth patterns in children in the second year
      of life in high-resource settings are warranted.

PMID- 28449385
TI  - Linkage to HIV care after home-based HIV counselling and testing in sub-Saharan
      Africa: a systematic review.
AB  - BACKGROUND: Home-based HIV counselling and testing (HBHCT) has the potential to
      increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to
      HIV care after HBHCT are scarce. We conducted a systematic review of linkage to
      care after HBHCT in SSA. METHODS: Five databases were searched for studies
      published between 1st January 2000 and 19th August 2016 that reported on linkage
      to care among adults newly identified with HIV infection through HBHCT. Eligible
      studies were reviewed, assessed for risk of bias and findings summarised using
      the PRISMA guidelines. RESULTS: A total of 14 studies from six countries met the
      eligibility criteria; nine used specific strategies (point-of-care CD4 count
      testing, follow-up counselling, provision of transport funds to clinic and
      counsellor facilitation of HIV clinic visit) in addition to routine referral to
      facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1
      week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval
      (CI), 6.8-9.8%] to 99.1% (95% CI, 96.9-99.9%). Linkage was generally lower (<33%)
      if HBHCT was followed by referral only, and higher (>80%) if additional
      strategies were used. Only one study assessed linkage by means of a randomised
      trial. Five studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART
      eligibility and initiation. CTX uptake among those eligible ranged from 0% to
      100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1
      21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged
      from 14.3% (95% CI, 0.36-57.9%) to 94.9% (95% CI, 91.3-97.4%). Additional linkage
      strategies, whilst seeming to increase linkage, were not associated with higher
      uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome
      ascertainment bias. A pooled analysis was not performed because of heterogeneity
      across studies with regard to design, setting and the key variable definitions.
      CONCLUSION: Only few studies from SSA investigated linkage to care among adults
      newly diagnosed with HIV through HBHCT. Linkage was often low after routine
      referral but higher if additional interventions were used to facilitate it. The
      effectiveness of linkage strategies should be confirmed through randomised
      controlled trials.

PMID- 28449386
TI  - Influence of a 2- to 6-year physical education intervention on scholastic
      performance: The CHAMPS study-DK.
AB  - The aim of this study was to investigate the influence of a school-based
      intervention with a tripling of physical education (PE) lessons from two (90
      minutes) to six lessons per week (270 minutes) on scholastic performance. This
      study is part of the CHAMPS study-DK, a quasi-experimental study that began in
      2008. The intervention group consisted of six schools, and the control group
      consisted of four matched schools (mean age at baseline=8.4 years, kindergarten
      class fourth grade). Academic performance was extracted from the national test
      system from 2010 to 2014 (Math and Danish were measured at third and sixth, and
      second, fourth and sixth grades, respectively). Participants included 1888
      students participating in at least one scholastic performance test. Linear mixed
      models were applied to test for differences between groups and adjusted for known
      confounders. No significant differences were observed between groups in the
      academic performance tests (control group reference); Danish second grade beta=
      1.34 (95% CI -9.90, 7.22), fourth grade beta=0.22 (95% CI -6.12, 6.56), sixth
      grade beta=1.03 (95% CI -5.02, 7.08), and all grades combined beta=0.28 (95% CI 
      5.74, 6.31) and Math third grade beta=-2.87 (95% CI -9.65, 3.90), sixth grade
      beta=0.99 (95% CI -7.36, 9.34) and combined beta=-1.20 (95% CI -8.10, 5.71). In
      conclusion, no significant differences were observed between intervention and
      control schools for scholastic performance. Importantly, there were no negative
      effects of additional PE on scholastic outcomes, despite more PE and longer
      school days for intervention children.

PMID- 28449387
TI  - Sustaining Nurse-Led Task-Shifting Strategies for Hypertension Control: A Concept
      Mapping Study to Inform Evidence-Based Practice.
AB  - BACKGROUND: The use of task-shifting is an increasingly widespread delivery
      approach for health interventions targeting prevention, treatment, and control of
      hypertension in adults living in sub-Saharan Africa (SSA). Addressing a gap in
      the literature, this research examined the sustainability of an ongoing task
      shifting strategy for hypertension (TASSH) from the perspectives of community
      health nurses (CHNs) implementing the program. METHODS: We used concept-mapping,
      a mixed-methods participatory approach to understand CHNs' perceptions of
      barriers and enablers to sustaining a task-shifting program. Participants
      responded to focal prompts, eliciting statements regarding perceived barriers and
      enablers to sustaining TASSH, and then rated these ideas based on importance to
      the research questions and feasibility to address. Twenty-eight community health
      nurses (21 women, 7 men) from the Ashanti region of Ghana completed the concept
      mapping process. RESULTS: Factors influencing sustainability were grouped into
      five categories: Limited Drug Supply, Financial Support, Provision of Primary
      Health Care, Personnel Training, and Patient-Provider Communication. The limited
      supply of antihypertensive medication was considered by CHNs as the most
      important item to address, while providing training for intervention personnel
      was considered most feasible to address. LINKING EVIDENCE TO ACTION: This study's
      findings highlight the importance of examining nurses' perceptions of factors
      likely to influence the sustainability of evidence-based, task-shifting
      interventions. Nurses' perceptions can guide the widespread uptake and
      dissemination of these interventions in resource-limited settings.

PMID- 28449388
TI  - Unobserved health care expenditures: How important is censoring in register data?
AB  - Accurate information on individuals' health service use is important for
      evaluating health policies and analyzing health care demand. Although register
      data are considered to be more reliable than survey data, little is known about
      the extent and effect of censoring of the expenditure distribution in register
      data. We exploit a recent change in the health provider remuneration system in
      several Swiss cantons to empirically investigate whether censoring occurs when
      individuals do not have to disclose their health service use below their
      deductible level. Applying a difference-in-differences approach, we find that
      between CHF 6.70 (1.7%) to CHF 9.64 (2.4%) of all health service use paid out-of
      pocket are not observed (per capita per year). This effect seems to be driven by
      high-deductible plans where observed out-of-pocket expenditures declined by CHF
      30.34 (7.6%) after the change. Although statistically significant, these effects
      are almost negligible in economic terms. We therefore concluded that, if
      anything, censoring is a very limited issue in Swiss health insurance claims
      data.

PMID- 28449389
TI  - Mindfulness training for parents of children with special needs: Guidance for
      nurses in mental health practice.
AB  - PROBLEM: Parents of children with special needs encounter specific challenges in
      carrying out their caregiving roles. They experience difficulty accepting their
      children due to unrealistically high expectations. Mindfulness training (MT) may
      increase parental psychological well-being and acceptance. OBJECTIVE: The purpose
      of this article is to examine the evidence-base for the effectiveness of MT in
      enhancing psychological well-being for parents of children with special needs as
      a foundation for guidance for nurses in mental health practice. METHODS: A
      literature review of relevant research studies was undertaken using specific
      inclusion criteria. The literature was derived from three databases that
      identified 56 articles narrowed to 5, which met inclusion criteria. FINDINGS: The
      studies indicated that cultivating a more mindful way of parenting is associated
      with reduced stress, anxiety, and depression. Parents experienced increased
      mindful awareness and improved psychological well-being, and they were more
      accepting of their children. Their children also had fewer behavior problems and
      enhanced positive interaction with their parents. Because mindfulness
      interventions fall within the scope of independent nursing practice, nurses can
      play a significant role in applying mindfulness to promote psychological well
      being in parents who have children with special needs.

PMID- 28449390
TI  - Partial tibial nerve transfer to tibialis anterior for traumatic peroneal nerve
      palsy.
AB  - BACKGROUND: Partial tibial nerve transfer to the motor branches of tibialis
      anterior is an emerging reconstructive technique for the treatment of traumatic
      common peroneal nerve (CPN) injury; however, few papers in the literature
      describe clinical outcomes. METHODS: A prospective single-surgeon series of nine
      consecutive patients who underwent partial tibial nerve transfers to the motor
      branches of tibialis anterior for traumatic CPN injuries between 2008 and 2014.
      Eight patients were male and the average age at operation was 28.2 years old
      (range 21-39). All nine patients experienced high-energy CPN injuries. The
      average time to operation was 5.8 months (range 1-10) and all patients scored M0
      for ankle dorsiflexion preoperatively according to the Medical Research Council
      (MRC) grading system. Outcome parameters included time since operation,
      postoperative MRC grade for ankle dorsiflexion, and the use of an orthosis for
      walking. RESULTS: Seven of nine patients achieved an MRC grade of >=M4, allowing
      for active dorsiflexion against gravity and some resistance, by a mean of 16.7
      months postoperatively (range 8-26) and no longer required an orthosis for
      walking. No complications were recorded during the procedures, nor were any
      compromises to the tibial nerve donor site during follow-up. No patients were
      lost to follow-up with an average follow-up period of 30.8 months (range 15-61).
      CONCLUSIONS: This series provides good evidence that this evolving reconstructive
      technique may achieve excellent results and should be considered in traumatic
      common peroneal nerve injuries that would traditionally rely on conventional
      nerve grafting alone.

PMID- 28449391
TI  - Flexible, Semitransparent, and Inorganic Resistive Memory based on BaTi0.95
      Co0.05 O3 Film.
AB  - Perovskite ceramics and single crystals are commonly hard and brittle due to
      their small maximum elastic strain. Here, large-scale BaTi0.95 Co0.05 O3 (BTCO)
      film with a SrRuO3 (SRO) buffered layer on a 10 um thick mica substrate is
      flexible with a small bending radius of 1.4 mm and semitransparent for visible
      light at wavelengths of 500-800 nm. Mica/SRO/BTCO/Au cells show bipolar resistive
      switching and the high/low resistance ratio is up to 50. The resistive-switching
      properties show no obvious changes after the 2.2 mm radius memory being
      written/erased for 360 000 cycles nor after the memory being bent to 3 mm radius
      for 10 000 times. Most importantly, the memory works properly at 25-180  degrees
      C or after being annealed at 500  degrees C. The flexible and transparent oxide
      resistive memory has good prospects for application in smart wearable devices and
      flexible display screens.

PMID- 28449392
TI  - Osmotic stress decreases complexity underlying the electrophysiological dynamic
      in soybean.
AB  - Studies on plant electrophysiology are mostly focused on specific traits of
      single cells. Inspired by the complexity of the signalling network in plants, and
      by analogy with neurons in human brains, we sought evidence of high complexity in
      the electrical dynamics of plant signalling and a likely relationship with
      environmental cues. An EEG-like standard protocol was adopted for high-resolution
      measurements of the electrical signal in Glycine max seedlings. The signals were
      continuously recorded in the same plants before and after osmotic stimuli with a 
      2 MPa mannitol solution. Non-linear time series analyses methods were used as
      follows: auto-correlation and cross-correlation function, power spectra density
      function, and complexity of the time series estimated as Approximate Entropy
      (ApEn). Using Approximate Entropy analysis we found that the level of temporal
      complexity of the electrical signals was affected by the environmental
      conditions, decreasing when the plant was subjected to a low osmotic potential.
      Electrical spikes observed only after stimuli followed a power law distribution,
      which is indicative of scale invariance. Our results suggest that changes in
      complexity of the electrical signals could be associated with water stress
      conditions in plants. We hypothesised that the power law distribution of the
      spikes could be explained by a self-organised critical state (SOC) after osmotic
      stress.

PMID- 28449394
TI  - Iowa Satisfaction with Anesthesia Scale for emergency medicine procedures.

PMID- 28449393
TI  - A phase 1 study of the c-Met inhibitor, tivantinib (ARQ197) in children with
      relapsed or refractory solid tumors: A Children's Oncology Group study phase 1
      and pilot consortium trial (ADVL1111).
AB  - BACKGROUND: The c-Met receptor tyrosine kinase is dysregulated in many pediatric
      cancers. Tivantinib is an oral small molecule that inhibits the c-Met receptor
      tyrosine kinase. A phase 1 and pharmacokinetic (PK) trial evaluating tivantinib
      was conducted in children with relapsed/refractory solid tumors. METHODS: Oral
      tivantinib capsules were administered twice daily with food, continuously in 28
      day cycles. Dose levels 170, 200, and 240 mg/m2 /dose were evaluated using a
      rolling-six design (Part A). In Part B, subjects received tivantinib powder
      sprinkled on food at the recommended phase 2 dose (RP2D) from Part A. PK, CYP2C19
      genotyping, and baseline tumor tissue c-Met expression were analyzed. RESULTS:
      Thirty-six patients were enrolled: 20 in Part A, 6 in a PK expansion cohort, and
      10 in Part B. Fifteen patients had primary central nervous system tumors and 21
      had solid tumors. In Part A, there were no dose-limiting toxicities. One grade 4
      intracranial hemorrhage occurred in a patient with a progressive brain tumor in
      the expanded PK cohort (240 mg/m2 ). PK analysis showed marked interpatient
      variability (20-fold) in the Cmax and AUC0-8h across all dose levels. Sprinkling
      tivantinib powder over food did not alter exposure. Membranous and total c-Met
      expression was moderate (2), low (4), or not detected (26). Two patients had
      stable disease as the best response. CONCLUSIONS: The RP2D of tivantinib given
      with food in children with refractory solid tumors is 240 mg/m2 /dose. PK of
      tivantinib in children demonstrated high variability. Objective responses were
      not observed in this phase 1 trial.

PMID- 28449395
TI  - Breast milk IgA to foods has different epitope specificity than serum IgA
      Evidence for entero-mammary link for food-specific IgA?
AB  - BACKGROUND: We have previously shown that maternal cow's milk (CM) elimination
      results in downregulation of CM-specific IgA antibody levels in BM, but not in
      serum, suggesting that an entero-mammary link may exist for food-specific
      antibody-secreting cells. OBJECTIVE: We sought to investigate whether food
      specific IgA epitope profiles differ intra-individually between mother's serum
      and BM. We also examined how infants' food epitope-specific IgA develops in early
      infancy and the relationship of IgA epitope recognition with development of cow's
      milk allergy (CMA). METHODS: We measured specific IgA to a series of overlapping
      peptides in major CM allergens (alphas1 -, alphas2 -, beta- and kappa-caseins and
      beta-lactoglobulin) in paired maternal and infant serum as well as BM samples in
      31 mother-infant dyads within the first 15 post-partum months utilizing peptide
      microarray. RESULTS: There was significant discordance in epitope specificity
      between BM and maternal sera ranging from only 13% of sample pairs sharing at
      least one epitope in alphas1 -casein to 73% in kappa-casein. Epitope-specific IgA
      was detectable in infants' sera starting at less than 3 months of age. Sera of
      mothers with a CMA infant had increased binding of epitope-specific IgA to CM
      proteins compared to those with a non-CMA infant. CONCLUSION & CLINICAL
      RELEVANCE: These findings support the concept that mother's milk has a distinct
      antifood antibody repertoire when compared to the antibody repertoire of the
      peripheral blood. Increased binding of serum epitope-specific IgA to CM in
      mothers of infants with CMA may reflect inherited systemic immunogenicity of CM
      proteins in these families, although specific IgA in breast milk was not
      proportionally up-regulated.

PMID- 28449396
TI  - Exploring guideline adaptation strategy for Turkey: Is "ADAPTE" feasible or does
      it need adaptation as well?
AB  - RATIONALE, AIMS, OBJECTIVES: Clinical Practice Guidelines are mostly developed by
      3 methods; namely, de novo, adoption, and adaptation. Nonpublished studies and
      authors experience shows that most guidelines in Turkey are either by adoption or
      by adaptation. There is no available local tool for adaptation, so the process is
      not standardized and most of the time not explicitly defined. The objective of
      this study is to search for international guideline adaptation tools and test
      their feasibility in Turkish context, to serve a final goal of developing a
      unique local strategic tool for guideline adaptation. METHODS: The methodological
      design of this study includes selection of an international tool for Clinical
      Practice Guideline adaptation, piloting this tool with selected Turkish
      guidelines, identifying the feasibility of this tool and exploring the needs for
      adaptation of the tool, drawing recommendations for adaptation of the strategies,
      and validation of the process by local experts. RESULTS: The study from planning
      phase to finalizing the guidance, including pilot studies and panel but excluding
      translation of ADAPTE, lasted 18 months. Nine researchers were involved in the
      adaptation process and 15 more experts were involved in the validation panel.
      Following the suggestions of the research team on modifications and validation
      through the expert panel; 2 steps of the ADAPTE toolkit were rejected, 2 steps
      were accepted by modification, 7 steps were accepted by additional
      recommendations. In addition, 2 tools were suggested to be added to the toolkit.
      CONCLUSION: This is the first study on adaptation of guidelines in Turkey. Pilot
      adaptation of 2 guidelines with ADAPTE revealed that ADAPTE is a useful and
      feasible tool in Turkish setting, but might require certain changes in
      recommendations and revision of tools.

PMID- 28449397
TI  - Differential proteome profiling in the hippocampus of amnesic mice.
AB  - Amnesia or memory loss is associated with brain aging and several
      neurodegenerative pathologies including Alzheimer's disease (AD). This can be
      induced by a cholinergic antagonist scopolamine but the underlying molecular
      mechanism is poorly understood. This study of proteome profiling in the
      hippocampus could provide conceptual insights into the molecular mechanisms
      involved in amnesia. To reveal this, mice were administered scopolamine to induce
      amnesia and memory impairment was validated by novel object recognition test.
      Using two-dimensional gel electrophoresis coupled with MALDI-MS/MS, we have
      analyzed the hippocampal proteome and identified 18 proteins which were
      differentially expressed. Out of these proteins, 11 were downregulated and 7 were
      upregulated in scopolamine-treated mice as compared to control. In silico
      analysis showed that the majority of identified proteins are involved in
      metabolism, catalytic activity, and cytoskeleton architectural functions. STRING
      interaction network analysis revealed that majority of identified proteins
      exhibit common association with Actg1 cytoskeleton and Vdac1 energy transporter
      protein. Furthermore, interaction map analysis showed that Fascin1 and Coronin 1b
      individually interact with Actg1 and regulate the actin filament dynamics. Vdac1
      was significantly downregulated in amnesic mice and showed interaction with other
      proteins in interaction network. Therefore, we silenced Vdac1 in the hippocampus
      of normal young mice and found similar impairment in recognition memory of Vdac1
      silenced and scopolamine-treated mice. Thus, these findings suggest that Vdac1
      mediated disruption of energy metabolism and cytoskeleton architecture might be
      involved in scopolamine-induced amnesia.

PMID- 28449398
TI  - Feeding-induced phenol production in Capsicum annuum L. influences Spodoptera
      litura F. larval growth and physiology.
AB  - We studied the role of induced plant phenols as a defense response to insect
      herbivory. Phenolic compounds were induced in Capsicum annuum L., the source of
      many culinary peppers, after feeding by different stages of the insect pest,
      Spodoptera litura F. The phenols were identified and quantified using high
      performance liquid chromatography (HPLC) and effects produced by these phenols on
      larval development were studied. Vanillic acid was identified in plants
      challenged by second, fourth, and fifth instar larvae, but not in plants
      challenged by third instar nor unchallenged plants. Syringic acid production was
      induced in chili plants infested with second (0.429 +/- 0.003 MUg/g fresh weight,
      fourth (0.396 +/- 0.01 MUg/g fresh weight), and fifth instar (5.5 +/- 0.06 MUg/g
      fresh weight) larvae, compared to untreated plants (0.303 +/- 0.01 MUg/g fresh
      weight) plants. Leaves surface treated with the rutin deterred oviposition.
      Dietary exposure to chlorogenic acid, vanillic acid, syringic acid, sinapic acid,
      and rutin led to enhanced activities of detoxifying enzymes, beta-glucosidase,
      carboxyl esterase, glutathione S-transferase, and glutathione reductase in the
      midgut tissues of all the larval instars, indicating the toxic nature of these
      compounds. Protein carbonyl content and acetylcholinesterase activity was
      analyzed to appreciate the role of induced plant phenols in insect protein
      oxidation and terminating nerve impulses.

PMID- 28449399
TI  - Comparative transcriptomic analysis of Bombyx mori fat body tissue following
      dietary restriction.
AB  - Dietary restriction (DR) refers to a reduction in food intake to induce
      undernutrition but not malnutrition, which extends the lifespan of multiple
      species. Although there are invertebrate aging models, such as the Caenorhabditis
      elegans and Drosophila melanogaster, aging studies in Lepidoptera are few in
      number and the underlying life-extending molecular mechanisms are not clear.
      Research on a broader range of animals is necessary to support generalizations on
      mechanisms of aging and rates of aging. The aim of this study was to further
      investigate genes and pathways associated with DR in Bombyx mori. Here, we used
      mRNA deep sequencing (RNA-seq) to further investigate genes and pathways
      associated with DR. The transcriptome profiles showed that most of the
      differentially expressed genes were upregulated following DR, and genes involved
      in amino acid and protein metabolism, RNA metabolism and translation, energy
      metabolism, nitrogen metabolism, and juvenile hormone pathway-related proteins
      were particularly affected. DR also affects the metabolism of uric acid and urea,
      which accumulated in silkworm following DR. We speculate that this may not be due
      to activation of uric acid biosynthesis, but rather by downregulating the
      degradation of uric acid and urea. These results may help us to understand the
      mechanisms by which DR prolong lifespan in insects and other animals.

PMID- 28449400
TI  - A Novel Implementation Strategy in Residential Care Settings to Promote EBP:
      Direct Care Provider Perceptions and Development of a Conceptual Framework.
AB  - BACKGROUND: Innovative approaches are required to facilitate the adoption and
      sustainability of evidence-based care practices. We propose a novel
      implementation strategy, a peer reminder role, which involves offering a brief
      formal reminder to peers during structured unit meetings. AIMS: This study aims
      to (a) identify healthcare aide (HCA) perceptions of a peer reminder role for
      HCAs, and (b) develop a conceptual framework for the role based on these
      perceptions. METHODS: In 2013, a qualitative focus group study was conducted in
      five purposively sampled residential care facilities in western Canada. A
      convenience sample of 24 HCAs agreed to participate in five focus groups.
      Concurrent with data collection, two researchers coded the transcripts and
      identified themes by consensus. They jointly determined when saturation was
      achieved and took steps to optimize the trustworthiness of the findings. Five
      HCAs from the original focus groups commented on the resulting conceptual
      framework. RESULTS: HCAs were cautious about accepting a role that might alienate
      them from their co-workers. They emphasized feeling comfortable with the peer
      reminder role and identified circumstances that would optimize their comfort
      including: effective implementation strategies, perceptions of the role, role
      credibility and a supportive context. These intersecting themes formed a peer
      reminder conceptual framework. LINKING EVIDENCE TO ACTION: We identified HCAs'
      perspectives of a new peer reminder role designed specifically for them. Based on
      their perceptions, a conceptual framework was developed to guide the
      implementation of a peer reminder role for HCAs. This role may be a strategic
      implementation strategy to optimize the sustainability of new practices in
      residential care settings, and the related framework could offer guidance on how
      to implement this role.

PMID- 28449401
TI  - Chinese consensus on the diagnosis and management of autoimmune hepatitis (2015).

PMID- 28449402
TI  - Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin
      glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week,
      randomised, open-label trial.
AB  - AIM: To determine whether lixisenatide, a prandial short-acting glucagon-like
      peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular
      hyperfiltration in patients with type 2 diabetes mellitus (T2DM) compared with
      insulin-glulisine (iGlu). METHODS: Postprandial renal haemodynamic effects of 8
      week treatment with lixisenatide 20 ug vs once-daily titrated iGlu were measured
      in 35 overweight patients with T2DM inadequately controlled on insulin-glargine,
      with or without metformin [mean +/- SD age 62 +/- 7 years, HbA1c 8.0% +/- 0.9%,
      estimated glomerular filtration rate (GFR) 85 +/- 12 mL/min/1.73 m2 , median
      (IQR) urinary albumin/creatinine ratio 1.5 (0.9-3.0) mg/mmol]. After a
      standardised breakfast, GFR (primary endpoint) and effective renal plasma flow
      (ERPF) were determined by inulin and para-aminohippuric acid renal clearance,
      respectively, based on timed urine sampling. Intrarenal haemodynamic functions
      were estimated using Gomez equations. RESULTS: Compared with iGlu, lixisenatide
      did not affect GFR [+0.1 mL/min/1.73 m2 (95% CI -9 to 9)], ERPF [-17 mL/min/1.73
      m2 (-61 to 26)], other (intra-)renal haemodynamics or renal damage markers, but
      increased fractional sodium excretion [+0.25% (0.09-0.41)] and urinary pH [+0.7
      (0.3-1.2)]. Plasma renin, angiotensin-II and aldosterone were unchanged.
      Lixisenatide and iGlu reduced HbA1c similarly, by 0.8% +/- 0.1% and 0.6% +/-
      0.1%, respectively, while postprandial glucose was lower with lixisenatide (P =
      .002). Compared with iGlu, lixisenatide reduced bodyweight [-1.4 kg (-2.5 to 
      0.2)] and increased postprandial mean arterial pressure [+9 mm Hg (4-14)].
      CONCLUSION: Eight-week lixisenatide treatment does not affect postprandial (intra
      )renal haemodynamics compared with iGlu when added to insulin-glargine in
      patients with T2DM without overt nephropathy. Prolonged lixisenatide treatment
      has a sustained natriuretic effect, which is in contrast to previous reports on
      long-acting GLP-1RA, reduces body weight and increases postprandial blood
      pressure compared with iGlu. TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT02276196.

PMID- 28449403
TI  - Effects of malnutrition on treatment-related morbidity and survival of children
      with cancer in Nicaragua.
AB  - BACKGROUND: Most children with cancer live in resource-limited countries where
      malnutrition is often prevalent. We identified the relationship between
      malnutrition and treatment-related morbidity (TRM), abandonment of therapy, and
      survival of children with cancer in Nicaragua to better inform targeted
      nutritional interventions. PROCEDURE: We conducted a retrospective review of
      patients aged 6 months to 18 years with newly diagnosed acute lymphoblastic
      leukemia, acute myeloid leukemia (AML), Wilms tumor, Hodgkin lymphoma, or Burkitt
      lymphoma (BL) who were treated between January 1, 2004, and December 31, 2007 at
      Children's Hospital Manuel de Jesus Rivera in Managua, Nicaragua. Statistical
      analysis examined the relations among nutritional status and cancer type, risk
      category, TRM, and event-free survival (EFS). RESULTS: Sixty-seven percent of
      patients (189/282) were malnourished at diagnosis. Malnutrition was highest among
      patients with Wilms tumor (85.7%), BL (75%), and AML (74.3%). A total of 92.2% of
      patients (225/244) experienced morbidity during the first 90 days. Malnutrition
      was associated with severe infection (P = 0.033). Severely malnourished patients
      had >=grade 3 TRM on more days (P = 0.023) and were more likely to experience
      severe TRM on >50% of days (P = 0.032; OR, 3.27 [95% CI, 1.05-10.16]).
      Malnourished patients had inferior median EFS (2.25 vs. 5.58 years; P = 0.049),
      and abandoned therapy more frequently (P = 0.015). CONCLUSIONS: In Nicaragua,
      pediatric oncology patients with malnutrition at diagnosis experienced increased
      TRM, abandoned therapy more frequently, and had inferior EFS. Standardized
      nutritional evaluation of patients with newly diagnosed cancer and targeted
      provision of nutritional support are essential to decrease TRM and improve
      outcomes.

PMID- 28449404
TI  - Changes in prescribing and healthcare resource utilization after FDA Drug Safety
      Communications involving zolpidem-containing medications.
AB  - PURPOSE: Products containing the sedative/hypnotic zolpidem were subject to Drug
      Safety Communications (DSCs) in January and May 2013 describing the risk of next
      morning impairment and recommending lower starting doses particularly for women.
      This study aimed to assess whether zolpidem DSCs were associated with prescribing
      pattern changes between January 2011 and December 2013. METHODS: We assessed
      overall dispensings of zolpidem-containing products between January 2011 and
      December 2013 by conducting a time-series analysis. Analyses were stratified by
      gender because the DSC contained gender-specific information. Participants were
      patients drawn from the Optum Clinformatics data source of commercially insured
      people in the USA. We evaluated changes in mean prescribed dose of the two drugs
      and health care utilization metrics. RESULTS: Each month of the study, more than
      80 000 patients received a zolpidem-containing product and approximately one
      tenth as many received eszopiclone. The two DSCs did not affect the downward
      trajectory of new zolpidem prescriptions. However, there was an increase in use
      of lower-dose forms of zolpidem (30% increase, p < 0.001), coupled with a
      reduction in higher-dose forms (13% decrease, p = 0.03), so that the average dose
      decreased after the DSCs (from 9.7 mg to 9.4 mg, p < 0.001), a change that was
      not seen with eszopiclone (from 2.74 mg to 2.74 mg, p = 0.45). CONCLUSION: The
      DSCs related to zolpidem-containing products shifted prescribing toward the lower
      dose formulations, consistent with the recommendations in the DSCs. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 28449405
TI  - The impact of lesion location on dysphagia incidence, pattern and complications
      in acute stroke. Part 2: Oropharyngeal residue, swallow and cough response, and
      pneumonia.
AB  - BACKGROUND AND PURPOSE: Dysphagia is a well-known complication of acute stroke.
      Given the complexity of cerebral swallowing control it is still difficult to
      predict which patients are likely to develop swallowing dysfunction based on
      their neuroimaging. In Part 2 of a comprehensive voxel-based imaging study,
      whether the location of a stroke lesion can be correlated with further
      dysfunctional swallowing patterns, pulmonary protective reflexes and pneumonia
      was evaluated. METHODS: In all, 200 acute stroke cases were investigated applying
      flexible endoscopic evaluation of swallowing within 96 h from admission. Lesions
      were mapped using patients' computed tomography/magnetic resonance images and
      these were registered to a standard space. The percentage of lesioned volume of
      137 anatomically defined brain regions was determined on a voxel basis (FSL5.0).
      Region-specific odds ratios (ORs) were calculated with respect to the presence of
      oropharyngeal residue, delayed swallow response, insufficient cough reflex and
      occurrence of pneumonia during hospital stay. Colour-coded lesion location maps
      of brain regions with significant ORs were created (P < 0.05). RESULTS: Lesion
      maps for residue and impaired swallow response depicted parietal-temporal areas
      of the right hemisphere. Limbic structures in the right hemisphere and sensory
      regions on the left were associated with cough reflex disturbance. There was no
      overlap of lesion maps for impaired swallow response and insufficient cough
      reflex or pneumonia, but substantial overlap between the last two conditions.
      CONCLUSIONS: This study gives new insights on the cortical representation of
      single components of swallowing and airway protection behaviours. The lesion
      model may help to risk-stratify patients for dysphagia and pneumonia based on
      their brain scan.

PMID- 28449406
TI  - A Water-Stable Dual-Channel Luminescence Sensor for UO22+ Ions Based on an
      Anionic Terbium(III) Metal-Organic Framework.
AB  - A stable 3D TbIII -based metal-organic framework [Tb(BPDC)2 ]?(CH3 )2 NH2 (DUT
      101) was synthesized, and it is the first efficient dual-channel luminescence
      sensor for aqueous UO22+ ions. DUT-101 contains an anionic three-dimensional
      framework and protonated dimethylamine molecules embedded within the channels.
      The intense green emission of DUT-101 could be highly selectively and sensitively
      quenched by UO22+ ions even in the presence of other competing metal ions. A
      possible sensing mechanism was proposed based on both suppression of luminescence
      resonance energy transfer and enhancement of intermolecular electron transfer.
      Furthermore, visual green fluorescent test papers based on DUT-101 were
      fabricated and could be used to discriminate UO22+ ions among various metal ions.

PMID- 28449407
TI  - Simple and effective paediatric retrieval treatment.

PMID- 28449408
TI  - Prediabetes is associated with genetic variations in the gene encoding the Kir6.2
      subunit of the pancreatic ATP-sensitive potassium channel (KCNJ11): A case
      control study in a Han Chinese youth population.
AB  - BACKGROUND: The E23K variant of the potassium voltage-gated channel subfamily J
      member 11 (KCNJ11) gene has been reported to be associated with type 2 diabetes
      (T2D) in many populations. However, little is known about the role of E23K in the
      development of prediabetes in Chinese youth. METHODS: To investigate the role of
      E23K in the development of prediabetes, 279 subjects with prediabetes and 240
      normal controls (mean [+/- SD] age 18.1 +/- 3.2 and 17.8 +/- 4.3 years,
      respectively) were recruited to the study. Height, weight, and hip and waist
      circumferences were measured by trained physicians. Genotyping of KCNJ11
      polymorphisms and clinical laboratory tests to determine cholesterol,
      triglyceride (TG), blood glucose, and insulin levels were performed. RESULTS: The
      carrier rate of K23 allele-containing genotypes was higher for prediabetic than
      control subjects (P = 0.005). Logistic regression analyses revealed that higher
      body mass index percentiles (P = 0.013), lower insulin levels at 30 min during an
      oral glucose tolerance test (P = 0.001), a higher ratio of total cholesterol:
      high-density lipoprotein cholesterol (P = 0.001), and a K allele-containing
      genotype (P = 0.019) are independent risk factors for prediabetes in Chinese Han
      youth. Furthermore, K23 allele-containing genotypes were associated with impaired
      indices of insulin secretion and beta-cell function in female youth with
      prediabetes. These effects were not seen in male youth with prediabetes.
      CONCLUSIONS: The results confirm that the common E23K polymorphism of KCNJ11
      carries a higher susceptibility to the development of prediabetes in the Chinese
      Han population. The results suggest that E23K may have a greater effect on the
      development of T2D in female Chinese youth.

PMID- 28449409
TI  - Real Time Central Assessment of Kidney Transplant Indication Biopsies by
      Microarrays: The INTERCOMEX Study.
AB  - The authors conducted a prospective trial to assess the feasibility of real time
      central molecular assessment of kidney transplant biopsy samples from 10 North
      American or European centers. Biopsy samples taken 1 day to 34 years
      posttransplantation were stabilized in RNAlater, sent via courier overnight at
      ambient temperature to the central laboratory, and processed (29 h workflow)
      using microarrays to assess T cell- and antibody-mediated rejection (TCMR and
      ABMR, respectively). Of 538 biopsy samples submitted, 519 (96%) were sufficient
      for microarray analysis (average length, 3 mm). Automated reports were generated
      without knowledge of histology and HLA antibody, with diagnoses assigned based on
      Molecular Microscope Diagnostic System (MMDx) classifier algorithms and signed
      out by one observer. Agreement between MMDx and histology (balanced accuracy) was
      77% for TCMR, 77% for ABMR, and 76% for no rejection. A classification tree
      derived to provide automated sign-outs predicted the observer sign-outs with >90%
      accuracy. In 451 biopsy samples where feedback was obtained, clinicians indicated
      that MMDx more frequently agreed with clinical judgment (87%) than did histology
      (80%) (p = 0.0042). In 81% of feedback forms, clinicians reported that MMDx
      increased confidence in management compared with conventional assessment alone.
      The authors conclude that real time central molecular assessment is feasible and
      offers a useful new dimension in biopsy interpretation. ClinicalTrials.gov
      NCT#01299168.

PMID- 28449410
TI  - The impact of the Affordable Care Act on self-employment.
AB  - This paper estimates the impact of the implementation of the Affordable Care Act
      (ACA) in 2014 on the decision to be self-employed. Using data from the Current
      Population Survey, we employ two identification strategies. Utilizing prereform
      variation in state nongroup health insurance market regulations, we find that the
      ACA did not increase self-employment overall in states that lacked similar
      provisions in their nongroup markets prior to 2014. In specifications that
      utilize variation across individuals in characteristics that could make it harder
      for them to purchase insurance if they left their current employer, we also do
      not find that the ACA differentially increased self-employment. However, in
      states that lacked the ACA nongroup market provisions, we do find a statistically
      significant increase in the second year of implementation (when individuals had
      more time to adjust behavior and the exchanges functioned properly) among
      individuals eligible for insurance subsidies, suggesting that a combination of
      time to adjust, low uncertainty and low insurance costs may be necessary for
      nongroup health insurance reforms to impact self-employment.

PMID- 28449411
TI  - Spectroscopic Characterization of the Reaction Products between the Criegee
      Intermediate CH2 OO and HCl.
AB  - Pulsed Fourier-transform microwave experiments have been performed to probe the
      products resulting from the reaction between HCl and the simplest Criegee
      intermediate, CH2 OO, where the reaction is considered to be important in
      atmospheric chemistry. The experimentally determined rotational parameters
      interpreted with the help of quantum chemical calculations support the
      identification of chloro-methyl hydroperoxide molecule as the primary product of
      this reaction.

PMID- 28449413
TI  - Sporadic versus syndromic keratocysts-Can we predict treatment outcome? A review
      of 102 cysts.
AB  - OBJECTIVES: Keratocystic odontogenic tumor (KCOT) demonstrates variable growth
      mechanisms and biologic behavior, partly due to origin and histology. We looked
      for the most contributing factors in predicting outcome of treatment. SUBJECTS
      AND METHODS: We retrospectively reviewed 118 medical files of patients diagnosed
      with KCOT (by tissue biopsy before surgical treatment) with/without nevoid basal
      cell carcinoma syndrome (NBCCS) from 1995 to 2015. Data were recorded and
      analyzed statistically to determine the treatment-outcome correlation. KCOTs in
      NBCCS patients were termed "syndromic" and random KCOTs termed "sporadic."
      RESULTS: Of 102 cysts, 32 were diagnosed with NBCCS. Sporadic KCOTs were
      significantly larger upon diagnosis (p < .017). Factors most indicative of
      postsurgical complications are older age (p < .011), upper jaw location, and size
      of lesion >=9.5 cm2. Sporadic KCOTs significantly increased the chances of
      complications approximately threefold (p < .043). Higher recurrence rate was
      significant in syndromic cysts (47%) compared to sporadic cysts (20%) (p < .009).
      Recurrence time was 3 years on average. CONCLUSIONS: Postsurgical complications
      may be expected in: older patients, upper jaw location, extensive lesions, and
      sporadic KCOT. Most KCOT recurrence is diagnosed 3 years from treatment.

PMID- 28449412
TI  - Effects of age, gender, and body mass index on efficacy and hypoglycaemia
      outcomes across treat-to-target trials with insulin glargine 100 U/mL added to
      oral antidiabetes agents in type 2 diabetes.
AB  - AIMS: To analyse the effects of patient characteristics and different oral
      antidiabetes drug (OAD) use on standardised clinical outcomes in type 2 diabetes
      patients initiating insulin glargine 100 U/mL (Gla-100). MATERIALS AND METHODS:
      Patient-level data from 16 randomized, treat-to-target clinical trials that added
      Gla-100 to existing metformin (MET), sulfonylurea (SU) or metformin plus
      sulfonylurea (MET+SU) treatment in insulin-naive patients inadequately controlled
      by oral therapy were analysed and patients were followed for >=24 weeks. Change
      in glycated haemoglobin A1c (HbA1c) from baseline to week 24, other glycaemic
      endpoints and incidence of hypoglycaemia (overall, nocturnal, and severe) were
      analysed by age (<65 vs >=65 years), gender (male vs female), body mass index
      (BMI; <25 vs >=25 to <30 vs >30 kg/m2 ) and concomitant OAD (MET vs SU vs
      MET+SU). RESULTS: At baseline, the overall population (N = 3188) had a mean age
      of 57.7 years, BMI of 30.5 kg/m2 , HbA1c of 8.7%, fasting plasma glucose of 192
      mg/dL, and 52.7% were male. Younger and older patients had similar HbA1c
      reductions with Gla-100 and a similar risk of hypoglycaemia. Females and patients
      with BMI <25 kg/m2 were less likely to achieve HbA1c targets and more likely to
      experience hypoglycaemia, regardless of concomitant OAD. Adding Gla-100 to SU
      therapy (alone or in combination with MET) increased hypoglycaemia risk across
      all analyses. CONCLUSIONS: Our data suggest that female patients with type 2
      diabetes and normal-weight patients treated with Gla-100 and MET +/- SU are less
      likely to achieve glycaemic targets and, therefore, may require more clinical
      attention. Addition of Gla-100 to SU regimens may increase hypoglycaemia risk
      irrespective of age, gender, or BMI.

PMID- 28449414
TI  - Trisomy 18 and holoprosencephaly.

PMID- 28449416
TI  - Strengths and limitations of healthcare databases in the evaluation of
      hypoglycaemia.

PMID- 28449415
TI  - Socioeconomic determinants of growth in a longitudinal study in Nepal.
AB  - Socioeconomic status (SES) is associated with childhood anthropometry, but little
      is known about how it is associated with tissue growth and body composition. To
      investigate this, we looked at components of SES at birth with growth in early
      and mid-childhood, and body composition in a longitudinal study in Nepal. The
      exposure variables (material assets, land ownership, and maternal education) were
      quantified from questionnaire data before birth. Anthropometry data at birth, 2.5
      and 8.5 years, were normalized using WHO reference ranges and conditional growth
      calculated. Associations with child growth and body composition were explored
      using multiple regression analysis. Complete anthropometry data were available
      for 793 children. There was a positive association between SES and height-for-age
      and weight-for-age, and a reduction in odds of stunting and underweight for each
      increase in rank of SES variable. Associations tended to be significant when
      moving from the lower to the upper asset score, from none to secondary education,
      and no land to >30 dhur (~500 m2 ). The strongest associations were for maternal
      secondary education, showing an increase of 0.6-0.7 z scores in height-for-age
      and weight-for-age at 2.5 and 8.5 years and 0.3 kg/m2 in fat and lean mass
      compared to no education. There was a positive association with conditional
      growth in the highest asset score group and secondary maternal education, and
      generally no association with land ownership. Our results show that SES at birth
      is important for the growth of children, with a greater association with fat
      mass. The greatest influence was maternal secondary education.

PMID- 28449417
TI  - Iron and anemia in chronic kidney disease: New treatments changing old paradigms.

PMID- 28449419
TI  - Efficacy and safety of eptifibatide versus tirofiban in acute coronary syndrome
      patients: A systematic review and meta-analysis.
AB  - BACKGROUND: Glycoprotein IIb/IIIa inhibitors were the strongest available
      antiplatelet therapy and have been shown to reduce cardiac ischemic complications
      in patients undergoing percutaneous coronary intervention. However, evidences are
      still lacking on the superiority of eptifibatide over tirofiban or vice versa in
      patients with acute coronary syndrome. OBJECTIVE: To compare the efficacy and
      safety of eptifibatide and tirofiban used among patients with acute coronary
      syndrome by performing a systematic review and meta-analysis of randomized
      controlled trials. METHODS: A systematic search was conducted in Pubmed,
      Ovid/Medline, Ovid/Embase, Clinicaltrials.gov, CBM and CNKI to identify
      randomized controlled trials comparing eptifibatide with tirofiban for acute
      coronary syndrome until November 2015. The methodological quality was assessed
      with the Cochrane bias risk assessment tool. RESULTS: 1256 patients from 9
      randomized controlled trials were finally included. Compared with tirofiban,
      eptifibatide could reduce more risk of thrombolysis in myocardial infarction
      minor bleeding (RR 0.61, 95%CI 0.38, 0.98). However, no significant differences
      were observed for major adverse cardiac events (RR 0.41, 95%CI 0.15 to 1.12),
      major bleeding, thrombocytopenia in the two treatment groups. The relative
      treatment benefits were similar in subgroups of patients according to types of
      acute coronary syndrome, or undergoing percutaneous coronary intervention.
      CONCLUSION: Available evidence suggests that the safety of eptifibatide is
      slightly superior to tirofiban in patients with acute coronary syndrome, but no
      significant difference was observed on efficacy. Future studies should focus on
      the randomized controlled trials with larger sample, multi-center, long-term
      follow-up, high quality to compare the two drugs.

PMID- 28449420
TI  - Cytological features of warthin-like papillary thyroid carcinoma: A case report
      with review of previous cytology cases.
AB  - Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant
      of papillary thyroid carcinoma which mimics various benign and malignant lesions
      on thyroid aspiration cytology. As correct cytological diagnosis is the
      cornerstone for appropriate patient management, awareness of the salient
      cytomorphological characteristics of this tumor is essential. Here, we present
      cytological features of a case of WLPTC along with discussion of the common
      differential diagnoses and a brief review of the literature to ascertain the most
      consistent cytological findings of WLPTC. The present case also harboured
      BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC.

PMID- 28449418
TI  - HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron
      metabolism.
AB  - A classic response to systemic hypoxia is the increase in red blood cell
      production. This response is controlled by the prolyl hydroxylase domain/hypoxia
      inducible factor (HIF) pathway, which regulates a broad spectrum of cellular
      functions. The discovery of this pathway as a key regulator of erythropoiesis has
      led to the development of small molecules that stimulate the production of
      endogenous erythropoietin and enhance iron metabolism. This review provides a
      concise overview of the cellular and molecular mechanisms that govern HIF-induced
      erythropoietic responses and provides an update on clinical experience with
      compounds that target HIF-prolyl hydroxylases for anemia therapy.

PMID- 28449421
TI  - [The Role of MicroRNAs in Colorectal Cancer].
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer related deaths in
      the world. Many oncogenes and tumor suppressor genes are involved in the
      development of CRC. MicroRNAs (miRNAs) are a class of small, non-coding,
      endogenous RNAs in animals and plants. Recent studies have shown that miRNAs are
      associated with the mediation process of tumorigenesis, including inflammation,
      cell cycle, stress response, differentiation, apoptosis, migration, and invasion
      in cancer. These miRNAs have been linked to the development of CRC and recently
      studied as new potential biomarkers in the diagnosis and treatment for CRC.
      Specific miRNAs expression patterns help distinguish CRC from other colon-related
      diseases, and miRNAs can target the oncogenes and regulatory molecular pathways.
      Recent studies have demonstrated the restoration of tumor suppressive miRNAs and
      inhibition of oncogenic miRNAs for CRC treatment. Herein, we describe the
      diagnostic and therapeutic roles of miRNAs in CRC.

PMID- 28449422
TI  - The Effect of Anti-reflux Therapy on Patients Diagnosed with Minor Disorders of
      Peristalsis in High-resolution Manometry.
AB  - Background/Aims: Minor disorders of peristalsis are esophageal motility disorders
      categorized by the Chicago Classification (CC), version 3.0, which was announced
      in 2014. This study evaluated the efficacy of anti-reflux therapy in patients
      with minor peristaltic disorders. Methods: Patients with minor peristaltic
      disorders in accordance with CC v3.0 were included. We reviewed the medical
      records of patients with esophageal high-resolution manometry findings, and
      investigated the demographic and clinical information as well as the medical
      therapy. Thereafter, the response to treatment was assessed after at least 4
      weeks of treatment. Results: A total of 24 patients were identified as having
      minor disorders of peristalsis from January 2010 to December 2015. The mean
      follow-up period was 497 days, and there were 17 patients (70.8%) patients with
      ineffective esophageal motility. In terms of anti-reflux therapy, proton pump
      inhibitors (PPIs) with prokinetic agents and PPIs alone were prescribed in 19
      patients (79.2%) and 5 patients (20.8%), respectively. When the rate of response
      to the treatment was assessed, the responders rate (complete+satisfactory [>=50%]
      responses) was 54.2% and the non-responders rate (partial [<50%]+refractory
      responses) was 45.8%. Patients in the responder group were younger than those in
      the non-responder group (p=0.020). Among them, 13 patients underwent 24-hour
      multichannel intraluminal impedance-pH, and 10 patients (76.9%) were pathologic
      gastroesophageal reflux. Conclusions: The majority of esophageal minor
      peristaltic disorders were accompanied by gastroesophageal reflux, and therefore,
      they might respond to acid inhibitor. Further well-designed, prospective studies
      are necessary to confirm the effect of anti-reflux therapy in these patients.

PMID- 28449423
TI  - The Detection of Messenger RNA for Carcinoembryonic Antigen and Cytokeratin 20 in
      Peritoneal Washing Fluid in Patients with Advanced Gastric Cancer.
AB  - Background/Aims: Peritoneal micrometastasis is known to play an important role in
      the recurrence of gastric cancer. However, its effects remain equivocal. Herein,
      we examine the messenger RNA (mRNA) as tumor markers, carcinoembryonic antigen
      (CEA), and cytokeratin 20 (CK20), in peritoneal washing fluid. Moreover, we
      evaluate whether these results could predict the recurrence of gastric cancer
      following curative resection. Methods: We prospectively enrolled 132 patients
      with gastric cancers, who had received an operation, between January 2010 and
      January 2013. The peritoneal lavage fluid was collected at the operation field
      and semi-quantitative PCR was performed using the primers for CEA and CK20. We
      excluded patients with stage IA (n=28) early gastric cancer, positive cytologic
      examination of peritoneal washings (n=7), and those who were lost during follow
      up (n=18). Results: A total of 79 patients with gastric cancers were enrolled,
      and the mean follow-up period was 39.95+/-19.25 months (range, 5-72 months).
      According to the multivariate analysis, T4 stage at the initial diagnosis was
      significantly associated with recurrence. All cases of recurrence were CEA
      positive and 6 cases were CK20 positive. The positive and negative predictive
      values of CEA were 32.0% and 100%, respectively, whereas those of CK20 were 37.5%
      and 71.4%, respectively. Disease free survival of CK20-negative cases was 36.17+/
      20.28 months and that of CK20-positive cases was 32.06+/-22.95 months (p=0.39).
      Conclusions: It is unlikely that the real time polymerase chain reaction results
      of mRNA for CEA and CK20 in peritoneal washing fluid can predict recurrence.
      However, negative results can convince surgeons to perform curative R0 resection.

PMID- 28449424
TI  - Fecal Microbiota Transplantation for Refractory and Recurrent Clostridium
      difficile Infection: A Case Series of Nine Patients.
AB  - Background/Aims: Fecal microbiota transplantation (FMT) is a highly effective
      therapy for refractory and recurrent Clostridium difficile infection (CDI).
      Despite its excellent efficacy and recent widespread use, FMT has not been widely
      used in South Korea thus far. We describe our experience with FMT to treat
      refractory/recurrent CDI. Methods: We conducted a chart review of patients who
      underwent FMT for refractory/recurrent CDI at Inha University Hospital, between
      March 2014 and June 2016. The demographic information, treatment data, and
      adverse events were reviewed. FMT was administered via colonoscopy and/or
      duodenoscopy. All stool donors were rigorously screened to prevent infectious
      disease transmission. Results: FMT was performed in nine patients with
      refractory/recurrent CDI. All patients were dramatically cured. Bowel movement
      was normalized within one week after FMT. There were no procedure-related adverse
      events, except aspiration pneumonia in one patient. During the follow-up period
      (mean 11.4 months), recurrence of CDI was observed in one patient at one month
      after FMT due to antibiotics. Conclusions: FMT is a safe, well-tolerated and
      highly effective treatment for refractory/recurrent CDI. Although there are many
      barriers to using FMT, we expect that FMT will be widely used to treat
      refractory/recurrent CDI in South Korea.

PMID- 28449425
TI  - [The Clinical Significance of Serum Alpha-fetoprotein in Diagnosing
      Hepatocellular Carcinoma in a Health Screening Population].
AB  - Background/Aims: Serum alpha-fetoprotein (AFP) measurement is commonly included
      in a health check-up program in Korea. However, its benefits remain uncertain. We
      analyzed whether AFP measurement should be included in a general health check-up
      program to screen for hepatocellular carcinoma (HCC). Methods: A total of 36,552
      adults aged 18 years or older-who participated in a routine health examination
      including AFP determination between January 2009 and December 2009 at the Health
      Promotion Center, Samsung Medical Center, South Korea-were analyzed. High risk of
      HCC was defined as positivity for hepatitis B surface antigen, anti-hepatitis C
      virus antibody or having liver cirrhosis. Results: AFP level >10 ng/mL was
      observed in 27 participants (0.1%) and primary liver cancer was diagnosed in 9
      patients (6 HCC and 3 cholangiocarcinoma). Among 1,619 participants with high
      risk factors of HCC, AFP level >10 ng/mL was observed in 16 participants, of
      which, 4 diagnoses were made. Sensitivity, specificity, positive predictive
      value, and negative predictive value of AFP for HCC was 0.66, 0.99, 0.25 and
      0.99, respectively, for high risk participants. Among 34,933 participants without
      risk factors for HCC, 11 patients (<0.1%) showed elevated AFP levels above 10
      ng/mL, and no case was diagnosed with primary liver cancer during a median follow
      up period of 36 months (range: 0-48 months). Conclusions: AFP elevation was rare
      in participants without risk factors for HCC, and was unable to screen for HCC in
      this population. We discourage routine AFP measurements for asymptomatic adults
      without risk factors of HCC.

PMID- 28449426
TI  - [A Case of Intramural Hematoma of the Esophagus Mimicking Acute Coronary
      Syndrome].
AB  - Intramural hematoma of the esophagus is a rare condition that can be spontaneous
      or secondary to trauma, toxic ingestion, or intervention. If it is the
      spontaneous type, it usually presents initially with epigastric pain, hematemesis
      or dysphagia. We present a case of intramural hematoma of the esophagus mimicking
      acute coronary syndrome. A 63-year-old man presented with severe acute chest
      pain. He has four coronary stents that were inserted five years ago, from a
      different hospital, and is on dual antiplatelet agents. Coronary angiography was
      performed immediately under the suspicion of acute coronary syndrome, and we
      found that there was no obvious clogging of the coronary arteries. Next, chest
      computed tomography was performed due to suspected aortic dissection, and the
      result was also negative. Four days later, endoscopy was performed and intramural
      hematoma covered with large ulcers was diagnosed.

PMID- 28449427
TI  - Trichuris trichiura Infection in North Korean Defector Resulted in Chronic
      Abdominal Pain and Growth Retardation.
AB  - Trichuris trichiura infection is a common helminth infection, which is
      transmitted via soil, with worldwide distribution, especially in rural areas of
      developing countries. Occasionally, sporadic cases occur in non-endemic,
      developed areas due to the widespread of immigration. We experienced a case of
      Trichuris dysentery syndrome in a young North Korean defector, who had been
      suffering from chronic abdominal pain for 10 years. He is relatively short and
      thin compared with his older brother. Unexpectedly, the diagnosis, made by a
      colonoscopy, revealed numerous, small, white, and gently moving worms at the
      cecum and ascending colon. After 3 days of albendazole (400 mg once daily)
      administration, clinical symptoms subsided dramatically. On the follow-up
      colonoscopy, which was performed two months after the completion of his
      treatment, complete eradication was identified. Soil-transmitted helminths,
      including Trichuris trichiura, are disappearing becoming less prevalent in South
      Korea as a result of both national driving force and environmental improvement.
      However, these diseases should be considered when we meet foreign patients from
      developing countries, like North Korea, presenting chronic abdominal pain.
      Moreover, proper treatment of North Korean defectors and performing cohort
      studies of them would help to prepare for the possible unification era in the
      field of gastroenterology.

PMID- 28449428
TI  - A Rare Case of Pancreas Divisum Accompanied by Acute Pancreatitis Following
      Endoscopic Hemostasis for Duodenal Ulcer Bleeding.
AB  - Peptic ulcer bleeding is treated using endoscopic hemostasis using clips or
      bands. Pancreas divisum (PD), a congenital anomaly of the pancreas, usually has
      no clinical symptoms; however, pancreatitis may occur if there are disturbances
      in the drainage of pancreatic secretions. We report an unusual case of PD
      accompanied by acute pancreatitis, following endoscopic band ligation for
      duodenal ulcer bleeding. A 48-year-old woman was admitted to our hospital due to
      melena. An upper endoscopy revealed a small ulcer with oozing adjacent minor
      papilla. An endoscopic band ligation was performed on this lesion. Acute
      pancreatitis developed suddenly 6 hours after the band ligation and improved
      dramatically after removal of the band. Magnetic resonance
      cholangiopancreatography was performed, revealing complete PD. Endoscopic band
      ligation is known as the effective method for peptic ulcer bleeding; however, it
      should be used carefully in duodenal ulcer bleeding near the minor duodenal
      papilla due to the possibility of PD.

PMID- 28449429
TI  - Pancreatic Lymphoepithelial Cysts Diagnosed with Endosonography-guided Fine
      Needle Aspiration.
AB  - Although lymphoepithelial cysts (LECs) of the pancreas are benign lesions, most
      of them have been treated with surgical resection due to diagnostic difficulty.
      We report a 66-year-old woman diagnosed with pancreatic LECs. Abdominal
      ultrasound revealed two masses in the pancreas, which were not visible on the
      abdominal computed tomography. In an abdominal magnetic resonance imaging,
      pancreas lesions showed solid tumors, which revealed a low signal intensity on T1
      , moderate high signal intensity on T2 weighted images, and homogeneous delayed
      enhancement in the portal venous phase. Endosonography (EUS) revealed two
      hypoechoic round masses measuring 1.5 cm and 4.5 cm in the body and tail of the
      pancreas, respectively. EUS-guided fine needle aspiration (FNA) revealed squamous
      cells, amorphous keratinous debris, and lymphocytes. The patient was diagnosed
      with LECs of the pancreas. For the duration of the follow-up period of two years,
      imaging studies were unchanged. EUS-FNA is useful in making a definite diagnosis
      and avoiding unnecessary surgery. This is the first case of pancreatic LECs
      diagnosed with EUS-FNA in Korea.

PMID- 28449430
TI  - Poloxamer surface modified trimethyl chitosan nanoparticles for the effective
      delivery of methotrexate in osteosarcoma.
AB  - The present work is an effort to explore the poloxamer-modified trimethyl
      chitosan (TMC) encapsulated MTX for osteosarcoma treatment in order to improve
      the therapeutic efficacy and minimize severe toxicity associated with the
      clinical usage of MTX. The methotrexate-loaded pluronic-chitosan nanoparticles
      (MTCN) was nanosized and exhibited a controlled release of drug from the carrier
      system. The MTCN showed higher accumulation in cell cytoplasm region evident by
      the high red fluorescence indicating its uptake through energy-dependent
      endocytosis process. MTCN exhibited the increased cytotoxicity in MG63 cells
      compared free MTX due to its enhanced cellular uptake. Especially, MTCN exhibited
      a superior apoptosis effect with bright chromatin condensation and nuclear
      fragmentation was observed and showed remarkably higher apoptosis (~48%) compared
      to that of free drug. The results of this investigation clearly demonstrate that
      the poloxamer-modified trimethyl chitosan (TMC) seems to have a great potential
      as a drug carrier in cancer chemotherapy. The present research work offers
      immense scope for further exploitation of poloxamer-modified trimethyl chitosan
      (TMC) in future for the development of nanoparticulate drug delivery system for
      cancer chemotherapy.

PMID- 28449431
TI  - Three-dimensional printing of external airway splints for tracheomalacia.

PMID- 28449432
TI  - Should we reconsider dual antiplatelet therapy duration following bioresorbable
      scaffold angioplasty?

PMID- 28449433
TI  - FIRE or ICE for paroxysmal atrial fibrillation?-perspectives from the largest
      randomized evaluation of cryoballoon and radiofrequency ablation to date.

PMID- 28449434
TI  - Clinically suspected myocarditis with pseudo-infarct presentation: the role of
      endomyocardial biopsy.

PMID- 28449435
TI  - Non-surgical approach to the thoracic duct: a technique whose time has come.

PMID- 28449436
TI  - Bundle of care decreased ventilator-associated events-implications for ventilator
      associated pneumonia prevention.

PMID- 28449437
TI  - Early cerebrovascular events after transcatheter aortic valve replacement:
      patient- and procedure-specific predictors.

PMID- 28449438
TI  - Life ain't no SOFA-considerations after yet another failed clinical sepsis trial.

PMID- 28449439
TI  - Age before duty: the effect of storage duration on mortality after red blood cell
      transfusion.

PMID- 28449440
TI  - Composition and oxidative potential of PM2.5 pollution and health.

PMID- 28449441
TI  - Cancer prevention from the perspective of global cancer burden patterns.

PMID- 28449442
TI  - Systemic inflammatory response syndrome, sequential organ failure assessment, and
      quick sequential organ failure assessment: more pieces needed in the sepsis
      puzzle.

PMID- 28449443
TI  - Induced pluripotent stem cells, form in vitro tissue engineering to in vivo
      allogeneic transplantation.

PMID- 28449444
TI  - Pleurectomy/decortication for malignant pleural mesothelioma.

PMID- 28449445
TI  - The era of uniportal video-assisted thoracoscopic surgery.

PMID- 28449446
TI  - We must identify patients at risk for pre-hospital sudden cardiac arrest at the
      early phase of myocardial infarction.

PMID- 28449447
TI  - Osimertinib for advanced non-small cell lung cancer harboring EGFR mutation exon
      20 T790M, acquired resistant mutation for first- or second-generation EGFR-TKI.

PMID- 28449448
TI  - Analyzing competing risks in the treatment of lung cancer: a good start.

PMID- 28449449
TI  - Echocardiography to guide fluid therapy in critically ill patients: check the
      heart and take a quick look at the lungs.

PMID- 28449450
TI  - Stereotactic ablative body radiation therapy or surgery for operable early non
      small cell lung cancer patients: bound hand and foot to evidence.

PMID- 28449451
TI  - Malignant pleural mesothelioma: key determinants in tailoring the right treatment
      for the right patient.

PMID- 28449452
TI  - Robotic-assisted minimally invasive esophagectomy: is it advantageous over
      thoracoscopic esophagectomy?

PMID- 28449453
TI  - Cardiac regeneration using HLA-matched induced pluripotent stem cells-no monkey
      business, but still a long and winding road ahead.

PMID- 28449454
TI  - Analyses of trends in prevalence of congenital heart defects and folic acid
      supplementation.

PMID- 28449455
TI  - The many facets of diagnostic bronchoscopy for pulmonary ground glass nodules.

PMID- 28449456
TI  - Prognostic contribution of non-predominant solid and micropapillary components in
      lung adenocarcinomas.

PMID- 28449457
TI  - Nomogram prediction for the survival of the patients with small cell lung cancer.
AB  - BACKGROUND: Small cell lung cancer (SCLC) is a subtype of lung cancer with poor
      prognosis. In this study, we aimed to build a nomogram to predict the survival of
      individual with SCLC by incorporating significant clinical parameters. METHODS:
      The patients with SCLC were enrolled from the First Affiliated Hospital of
      Guangzhou Medical University (GMUFAH) between 2009 and 2013. We identified and
      incorporated the independent prognostic factors to build a nomogram to predict
      the survival of SCLC patients. The predictive accuracy and discriminative ability
      of the nomogram were evaluated by concordance index (C-index) and calibration
      curve. We also compared the accuracy of the built model with the 7th AJCC TNM and
      VALSG staging system. The nomogram was further validated in an independent cohort
      of 80 patients with SCLC from Cancer Center of Guangzhou Medical University
      (GMUCC) between 2009 and 2013. RESULTS: A total of 275 patients with SCLC were
      included in the primary cohort, and seven independent prognostic factors were
      identified including age, N stage, metastasis status, histology, platelets to
      lymphocyte ratio (PLR), neuron specific enolase (NSE) and CYFRA21-1 as
      independent prognostic factors after using Cox regression model. A nomogram
      incorporating these prognostic factors was subsequently built. The calibration
      curves for possibilities of 1-, 2-year overall survival (OS) revealed optimal
      agreement between nomogram prediction and actual observation. The C-index of this
      nomogram was higher than that of TNM and VALSG staging system in both primary and
      validation cohort (nomogram vs. TNM, primary cohort 0.68 vs. 0.65, P<0.01,
      validation cohort 0.66 vs. 0.62, P<0.05; nomogram vs. VALSG, primary cohort 0.68
      vs. 0.66, P<0.01, validation cohort 0.66 vs. 0.64, P<0.05). CONCLUSIONS: In this
      study, we established and validated a novel nomogram for the prediction of OS for
      the patients with SCLC. This model could provide more accurate individual
      prediction of survival probability of SCLC than the existing staging systems.

PMID- 28449458
TI  - Lower expression of platelet derived growth factor is associated with better
      overall survival rate of patients with idiopathic nonspecific interstitial
      pneumonia.
AB  - BACKGROUND: Idiopathic nonspecific interstitial pneumonia (INSIP) presents with
      varying degrees of interstitial inflammation and fibrosis exhibiting a uniform
      appearance. Lack of knowledge on the underlying mechanisms of INSIP has
      contributed to few effective treatment strategies. Our study is designed to
      explore aberrantly expressed cytokines involvement in INSIP development. METHODS:
      Oligo GEArray was employed to detect the expression of cytokines in INSIP
      patients, and idiopathic pulmonary fibrosis (IPF) was setup as isotype control.
      Real-time PCR and immunohistochemistry analysis were used to further confirm the
      expression of abnormally expressed cytokines. The correlationship between
      cytokines expression and overall survival rate of patients with IPF and INSIP
      were analyzed. RESULTS: From microarray detection, transforming growth factor
      beta-1 (TGF-beta1), fibroblast growth factor 10 (FGF10), and platelet derived
      growth factor (PDGF) were predominantly up-regulated in patients with INSIP. Real
      time PCR and immunohistochemistry also showed these cytokines was abnormally
      expressed in INSIP. In addition to, the clinical relevance analysis demonstrated
      relatively lower expression of PDGF patients had longer overall survival rate
      than those with higher expression of PDGF. CONCLUSIONS: Our study suggests that
      TGF-beta1, FGF10, and PDGF are required for the pathogenesis of INSIP, and may
      therefore be ideal targets in INSIP treatment. Moreover, INSIP patients with
      lower expression of PDGF had better survival rate.

PMID- 28449459
TI  - Endovascular repair of residual intimal tear or distal new entry after frozen
      elephant trunk for type A aortic dissection.
AB  - BACKGROUND: In patients with type A dissection, residual dissection and new
      distal entry tears following the frozen elephant trunk (FET) procedure adversely
      affect long-term prognosis. Management include open and endovascular repair,
      while clinical experience is limited. We evaluate the efficacy of thoracic
      endovascular aortic repair (TEVAR) in management of residual intimal tear or
      distal new entry tear following FET in patients with type A aortic dissection
      (TAAD). METHODS: Between May 2003 and April 2013, we performed FET and total arch
      replacement for 1,003 patients with TAAD. Among these, 23 patients (2.3%)
      required TEVAR for distal new entry (n=2) or residual intimal tear (n=21) at a
      mean of 2.0+/-1.6 years after FET. Mean age was 50.1+/-11.5 years. Marfan
      syndrome was seen in 2 patients (8.7%). RESULTS: Procedural success was 100%. The
      distal landing zone was above the 11th thoracic vertebra (T11) in 86.9% (20/23).
      Neither death nor any paraplegia or stroke occurred early after TEVAR. Follow-up
      was complete in 100% averaging 2.8+/-1.7 years (0.3-6.4). One non-Marfan patient
      died of distal aortic rupture at 4 months after TEVAR. No late stroke or
      paraplegia occurred. Survival was 95.7% (95% CI, 72.9-99.4%) at 3 and 5 years,
      respectively. CTA detected false lumen obliteration by thrombus around the
      endograft in the descending aorta in 91.3% (21/23) of patients. CONCLUSIONS:
      These early and midterm outcomes show the efficacy of TEVAR in obliterating the
      residual intimal tear or distal new entry after FET in patients with TAAD. TEVAR
      may be an alternative approach to distal new entry or residual intimal tear
      following FET for patients with TAAD.

PMID- 28449460
TI  - Role of bronchoprovocation tests in identifying exercise-induced
      bronchoconstriction in a non-athletic population: a pilot study.
AB  - BACKGROUND: Studies on diagnostic tests for exercise-induced bronchoconstriction
      (EIB) have centered around the asthmatic and elite athletic population.
      Traditionally, the exercise challenge test (ET) was recommended to assess EIB. We
      aimed to compare the performance of surrogate testing, mainly the hypertonic
      saline (HS) test, and methacholine challenge test (MCT) versus ET in identifying
      EIB among non-athletic subjects. METHODS: We prospectively recruited subjects who
      did not have confirmed active asthma, but who reported exercise-induced dyspnoea.
      The participants underwent HS and ET on separate days within two weeks. MCT
      performed within one year were obtained retrospectively from medical records. The
      sensitivity, specificity, and accuracy of each diagnostic test were calculated
      using ET as the gold standard. RESULTS: We recruited 27 participants (mean age
      20.6+/-2.5 years; 92.6% male). Five (18.5%) had a history of self-reported asthma
      prior to recruitment. Eleven participants (40.7%) had a positive ET test. The
      sensitivity, specificity and accuracy of HS in diagnosing EIB was 90.9%, 62.5%
      and 74.1%; while that of MCT was 88.9%, 83.3% and 85.7% respectively. Six
      subjects were positive to HS but had negative ET test. CONCLUSIONS: Both HS and
      MCT were found to be suitable alternatives to ET in screening for EIB in the non
      athletic population in this pilot study. Further large scale studies are required
      to confirm this finding. These tests have the potential to replace ET for the
      diagnosis of EIB in centres without ET equipment or facilities.

PMID- 28449461
TI  - Correlation of pleural effusions' grayscale sonographic parameters with fluid's
      analysis results.
AB  - BACKGROUND: Quantitative sonographic methods are used to assess pleural fluid's
      volume but no validated method exists for the measurement of the fluids' density
      and other qualitative values. We suggest a quantitative method, based on the
      pixel density of the pleural effusion's image, in order to evaluate the
      echogenicity of pleural effusion. METHODS: Pleural ultrasound (US) was performed
      in 62 patients with pleural effusion. Five consequent images of the pleural
      effusion were retrieved through axial view between the 9th and the 10th rib and
      one from the 10th rib through coronal view and converted into the high-resolution
      tagged image file format. The mean echo levels of all pixels of the pleural
      effusion and of the 10th rib were counted, and the hypoechogenicity index (HI)
      was calculated according to the following formula: HI = mean echo level of all
      pixels of the rib/mean echo levels of all pixels of pleural effusion. HI greater
      than 1 indicates pleural effusion's hypoechogenicity. Diagnostic thoracocentesis
      was performed and biochemical markers were measured. RESULTS: LDH, Cell Count, pH
      and Effusion Pixels (Mean) were both significantly correlated and associated with
      pixel ratio. Conversely, pixel ratio was not correlated with any other
      ultrasonography-derived parameter or biomarker. CONCLUSIONS: This study
      introduced HI as new index, which could demonstrate the inflammation density of
      pleural effusions. Moreover, when used in combination with classical biomarkers,
      HI might be a useful adjunct for the discrimination of pleural transudate.

PMID- 28449462
TI  - Pulmonary function tests findings and their diagnostic value in patients with
      IgG4-related disease.
AB  - BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated
      fibroinflammatory disorder that can affect most organs. To date, there have been
      no detailed assessments of pulmonary function in patients with IgG4-RD. In this
      study, we investigated pulmonary function in IgG4-RD patients and evaluated the
      value of pulmonary function tests (PFTs) in diagnosing IgG4-related respiratory
      disease (IgG4-RRD). METHODS: This was a retrospective study of 17 patients with
      IgG4-RD. The patients were divided into two groups: IgG4-RRD group and IgG4
      related disease extrapulmonary involvement (IgG4-RDEI) group. The PFT results
      were compared between the two groups. RESULTS: All patients in the IgG4-RRD group
      had pulmonary dysfunction. Five of 8 (62.5%) patients in the IgG4-RDEI group had
      pulmonary dysfunction, despite having normal thoracic computed tomography scans
      and no respiratory symptoms. Patients in both groups showed restrictive
      ventilatory dysfunction and abnormal diffusing capacity, and two patients in the
      IgG4-RRD group had obstructive ventilatory dysfunction. The incidence of
      diffusing capacity of the lung for carbon monoxide per liter of alveolar volume
      (DLCO/VA) decrease were significantly higher in the IgG4-RRD group than in the
      IgG4-RDEI group (P=0.029). DLCO/VA were significantly higher in the IgG4-RDEI
      than in the IgG4-RRD group (P=0.044), but otherwise, there were no significant
      differences. We report the first finding of a negative correlation between
      pulmonary diffusing capacity and total serum concentrations of IgG and IgG
      subclasses (IgG4, IgG3 and IgG2). CONCLUSIONS: DLCO/VA plays an important role
      for detecting lung involvement in IgG4-RD patients. The patient with high serum
      IgG may be more prone to respiratory involvement.

PMID- 28449463
TI  - Efficacy of nebulized colistin-based therapy without concurrent intravenous
      colistin for ventilator-associated pneumonia caused by carbapenem-resistant
      Acinetobacter baumannii.
AB  - BACKGROUND: Although there have been studies regarding the role of nebulized
      colistin as adjunctive therapy of ventilator-associated pneumonia (VAP) caused by
      carbapenem-resistant Acinetobacter baumannii (CRAB), a paucity of information on
      the efficacy of nebulized colistin as monotherapy is available. METHODS: We
      retrospectively reviewed 219 patients with VAP caused by CRAB treated with either
      intravenous (n=93) or nebulized colistin (n=126), from March 2010 to November
      2015. Factors related to clinical failure was assessed using propensity-score
      matched analysis. RESULTS: Of 219 patients, 39 patients from each group (n=78)
      were matched after covariate adjustment using propensity score. There were no
      significant differences in baseline characteristics as well as the rates of
      clinical failure between the propensity-score-matched groups [Odds ratio (OR),
      0.48; 95% confidence interval (CI), 0.19-1.19; P=0.11], while a significantly
      lower rate of acute kidney injury (AKI) during colistin therapy (18% vs. 49%,
      P=0.004) was observed in nebulized colistin group. In addition, multivariable
      analysis revealed that nebulized colistin did not significantly alter the rate of
      clinical failure [adjusted odds ratio (aOR), 0.36; 95% CI, 0.12-1.09; P=0.070].
      Instead, medical intensive care unit (ICU) admission (aOR, 7.14; 95% CI, 1.60
      32.00; P=0.010), and septic shock (aOR, 3.93; 95% CI, 1.27-12.17; P=0.018) were
      independent risk factors for clinical failure. CONCLUSIONS: Our findings suggest
      that nebulized colistin-based therapy, even without concurrent administration of
      intravenous colistin, may be an effective and safe treatment option for VAP
      caused by CRAB.

PMID- 28449464
TI  - The role of BioGlue in thoracic surgery: a systematic review.
AB  - BACKGROUND: BioGlue is a commonly used sealant in thoracic surgery. Prolonged air
      leak and presence of bronchopleural fistulae (BPF) are often encountered in
      clinical practice. We therefore, investigated the role and the efficacy of
      BioGlue in these scenarios. METHODS: A systematic review was conducted by
      searching Medline [1966-2016] and Cochrane Central Register of Controlled Trials
      (CENTRAL) [1999-2016] along with reference lists of the included studies.
      Included studies reported on thoracic surgery operations and use of BioGlue in
      thoracic surgical procedures, whereas excluded studies met at least one of the
      following criteria: non-English language studies, non-human population, studies
      on surgical specialties other than Thoracic surgery, reviews and meta-analyses
      and sealants other than BioGlue. RESULTS: Twelve studies with a total number of
      194 patients were included. Amongst them, 178 were treated for alveolar air leaks
      (AAL), 14 for BPF and 2 for lymphatic leaks. BioGlue was utilized at the time of
      initial operation in 172 (96.7%) patients for AAL, while at secondary
      intervention in 13 (92.9%) for BPF and 1 (50%) for lymphatic leak. In terms of
      AAL, only 2 out of 4 studies showed statistically significant reduction in
      duration of air leak, duration of intercostal drainage and length of stay (LOS)
      when BioGlue was applied. No complications were encountered after using BioGlue
      in sealing BPF, apart from the re-application of BioGlue in 3 cases. CONCLUSIONS:
      Although BioGlue has been shown to be efficient in treating AAL, it should be
      used with caution against BPF, despite encouraging preliminary results. Potential
      adverse effects must always be taken into consideration. Future randomized
      controlled trials are warranted in an attempt to establish its benefit in current
      clinical practice.

PMID- 28449465
TI  - Application of bronchoscope for the placement of nasoenteric feeding tube in
      patients with esophagectomy: a novel technique.
AB  - BACKGROUND: Currently the available techniques for the placement of nasoenteric
      feeding tube (NET), utilizing transnasal gastroscope are fast and tolerable,
      which is known as the most popular method. However, lots of hospitals don't have
      this endoscopic system. Bronchoscope, which is the basic respiratory endoscope,
      not only has the advantages of transnasal endoscopy, but also is popular in
      common hospitals. We used oxygen instillation as air supply plant of the
      bronchoscope, which broke its application limitation in digestive tract. The aim
      of this study is to evaluate the feasibility and availability of the method of
      placing NET with the bronchoscope in patients with esophagectomy. METHODS: From
      January 2013 to January 2016, a total of 48 patients with esophagectomy who
      underwent NET placement with the bronchoscope were included in our study.
      Information concerning age, gender, as well as background disease of the patients
      was collected. The success rate, procedure duration, and complications were
      recorded for each patient. RESULTS: The technique success rate reached 100%,
      procedure time ranged from 150 to 750 s, with an average time of 257 s. All
      patients tolerated well under local anesthesia, no complication of epistaxis or
      perforation occurred. CONCLUSIONS: The new technique of placing NET with the
      bronchoscope is fast, safe, effective, and well tolerated for patients with
      esophagectomy.

PMID- 28449466
TI  - Higher coronary artery calcification score is associated with adverse prognosis
      in patients with stable angina pectoris.
AB  - BACKGROUND: Coronary artery calcification (CAC) indicates the presence of
      atherosclerotic lesions and serves as a marker of prognosis in patients with
      coronary artery disease (CAD). This study evaluated the value of the CAC score
      for determining the prognosis of patients with stable angina pectoris (SAP).
      METHODS: A total of 106 consecutive patients with SAP were enrolled in this study
      from January 2011 to June 2014; from these patients, 640 multi-slice computer
      tomography (MSCT) samples were used to obtain CAC scores. The CAC scores were
      calculated according to the standard Agatston calcium scoring algorithm. All
      subjects were divided into a lower CAC score group (CAC score, <=300) and a
      higher CAC score group (CAC score, >300). Major adverse cardiac events (MACE)
      were followed-up, and the non-event survival time was recorded. The relationships
      between the CAC score and both clinical characteristics and MACE were then
      analysed. RESULTS: The CAC positively correlated with age and the creatinine (Cr)
      level. Compared with patients who received lower CAC scores, the rates of
      percutaneous coronary intervention (PCI), MACE and multi-vessel disease were
      significantly higher in patients who received higher CAC scores. The Cox
      regression analysis results showed that the CAC score [pre-standard deviation
      (SD)] was a risk factor for the no-event survival time [hazard ratio (HR), 3.06;
      95% confidence interval (CI), 1.47-6.38; P<0.05 for all]. However, the Kaplan
      Meier analysis suggested that the rates of MACE did not differ between patients
      who were treated with PCI plus medical therapy and those who were treated with
      optimal medical therapy alone in both the higher and lower CAC score groups.
      CONCLUSIONS: The CAC scores (per-SD) and MACE strongly and positively correlated
      in patients with SAP, and PCI was not related to the clinical prognosis of
      patients with SAP in either group.

PMID- 28449468
TI  - Pulmonary inflammatory myofibroblastic tumor versus IgG4-related inflammatory
      pseudotumor: differential diagnosis based on a case series.
AB  - BACKGROUND: Pulmonary inflammatory myofibroblastic tumor (IMT) has been
      considered as a synonym for inflammatory pseudotumor (IPT) for a long time.
      Recent studies have indicated that IMT and IgG4-related IPT are distinct
      diseases. However, no consensus criteria have been recommended. Here we propose a
      set of criteria for the differential diagnosis. METHODS: Twenty-six archived IMT
      and IgG4-related IPT samples were examined for histological characteristics and
      the expression of IgG, IgG4, SMA and ALK-1. Based on our proposed criteria, we
      reclassified the cases into either IMT or IgG4-related IPT group and compared the
      clinicopathological features, laboratory findings, overall survivals (OS) and
      disease-free survivals between groups to validate the effectiveness and
      dependability of the diagnostic criteria. RESULTS: The average age of IgG4
      related IPT group was higher than IMTs (48.82 vs. 39.22 years, P=0.031). In IMT
      group, tumors were characterized by bigger tumor sizes (3.47 vs. 2.22 cm,
      P=0.007), diffuse and total destroyed alveoli (88.89% vs. 17.65%, P=0.002), fewer
      lymphoid follicles (1.6/HPF vs. 3.0/HPF, P=0.045) and lower expression of IgG
      (74.7/HPF vs. 149.1/HPF; P<0.001). As an exclusion criterion of IgG4-related IPT,
      ALK-positivity was correlated with the higher cytological atypia (mean 3.7/HPF,
      P<0.001) and lesser lymphoid follicles (mean 1.2/HPF, P=0.021). And it's the
      first study to show the liner positive correlation between the lymphocytes +
      plasma cells count and IgG4-positive plasma cells count in these lesions
      (r=0.914, P<0.001). The negative correlation between the IgG4-positive plasma
      cells count and the expression of ALK-1 are reported for the first time as well
      (rs=-0.632, P=0.001). However, despite two patients with recurrence or metastasis
      were divided into IMT group, only borderline values were detected in the survival
      analysis (OS 88.89% vs. 100%, P=0.197, DFS 77.78% vs. 100.00%; P=0.056).
      CONCLUSIONS: The significant differences of clinicopathological characteristics
      between the IMTs and IgG4-related IPTs indicated that a combination of
      lymphocytes + plasma cells count, cytological atypia, IgG4 and ALK-1 staining
      will be helpful in differential diagnosis.

PMID- 28449467
TI  - Clinical analysis on 113 patients with lung cancer treated by percutaneous CT
      guided microwave ablation.
AB  - BACKGROUND: Lung Cancer is a primary tumor with poor prognosis. For early stage
      lung cancer, treatment options include surgical resection and microwave
      techniques. Percutaneous ablative techniques emerged as best therapeutic options
      for nonsurgical patients. METHODS: The aim of this study was to retrospectively
      analyze the clinical effect of CT-guided microwave ablation (MWA) treatment for
      patients with lung cancer who were not eligible for surgical resection. MWA was
      used to treat the tumor lesion of 113 patients with lung cancer who were in our
      hospital from Jan, 2013 to Jun, 2015. The median diameter of tumors was 3.1 cm
      (0.7-6 cm). Follow-up were paid to all the patients who received MWA therapy. The
      average follow-up was 22.1+/-8.6 months, and the median follow-up was 18 (7-40)
      months. RESULTS: All of 113 cases of patients with lung cancer experienced MWA
      therapy, and their tumors were found to have vacuolization, lower density and
      much smaller distinct shrinkage of tumor size with varying degrees. The local
      progression rate or relapse rate of the whole group was 15.9%. The counterpart of
      patients in the early-stage group was 5.7% (2/35), and the diameter of tumors in
      the two patients was more than 3 cm. The local progression rate or relapse rate
      of patients in advanced-stage group was 20.5%, wherein, 81.3% of local
      progression or relapse occurred to the patients with a tumorous diameter of more
      than 3 cm. The results indicated that the patients in advanced-stage group were
      vulnerable to local progression or relapse, the tumorous with greater diameter
      had higher incidence of local relapse. No mortality occurred within 30 days after
      surgery, the survival rate of patients in early-stage group at first, second,
      third year was respectively 97.1%, 94.1% and 84.7%. The counterpart of patients
      in advanced-stage group was respectively 93.6%, 87.7% and 71.7%. The difference
      of survival rate between both groups was not statistically significant (P=0.576).
      No perioperative deaths occurred, and the main complications i.e., fever,
      pneumothorax, pleural effusion, hemoptysis, pneumonia, and pain were slight and
      tolerable. CONCLUSIONS: MWA is an effective, safe and minimally invasive
      treatment for the patients with lung cancer who cannot be tolerated by surgical
      resection.

PMID- 28449469
TI  - CD90 positive cells exhibit aggressive radioresistance in esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: Cancer stem cells (CSCs) are widely abundant and considered to be an
      important factor in therapy resistance. They are also promising potential targets
      for conquering tumors. We explored the effects of radiation on stem cell-like
      tumor cells via the candidate marker CD90 to provide new ideas for the
      comprehensive treatment of esophageal squamous cell carcinoma (ESCC). METHODS: We
      constructed CD90 overexpression ESCC cells by lentiviral transfection and
      observed differences of toxicity, proliferation, clone number, apoptosis,
      migration, invasion, and in vivo tumor formation after irradiation. RESULTS: We
      found that the population of CD90 positive cells showed CSC-like characteristics,
      including increased tumorigenicity and migration in ESCC cells. We discovered
      that these capacities were strengthened to varying degrees in remaining cells
      after irradiation. Further exploration revealed that the genes of ETS-1 and its
      downstream target MMPs changed significantly, which are correlated with the
      epithelial mesenchymal transition (EMT). These effects lead to enhanced tumor
      growth and resistance to radiation. CONCLUSIONS: We show that CD90 overexpressing
      ESCC cells exhibit CSC-like characteristics and radiation resistance. From a
      clinical perspective, ESCC patients with tumors that have high CD90 expression,
      which inhibits apoptosis, could exhibit more local invasion as well as distant
      metastasis, indicating a poorer prognosis. Research on the mechanism of CD90 may
      provide a new perspective to therapeutic strategies for patients with ESCC.

PMID- 28449470
TI  - Impact of cyclooxygenase-2 and prostaglandin-E2 expression on clinical outcome
      after pulmonary metastasectomy.
AB  - BACKGROUND: Pulmonary metastasectomy (PM) is a standard procedure in the
      treatment of stage IV colorectal cancer (CRC). In most centers the indication for
      PM is solely based on clinical factors without taking the tumor biology into
      account. This results in diverse outcomes ranging from long-term remission to
      early recurrence. Inflammation is considered a hallmark of cancer development and
      progression. On the other hand the accessibility of CRC cells to the immune
      system reflects the grade of tumor aggressiveness. We sought to investigate the
      impact of cyclooxygenase-2 (COX-2) and prostaglandin-E2 (PGE2) expression in
      pulmonary metastases on different outcome parameters following PM. METHODS: From
      04/2009 to 11/2013 53 patients with complete PM for CRC were included in this
      single-center study. Tissue samples of resected pulmonary metastases and
      available corresponding primaries were collected and assessed by
      immunohistochemistry for COX-2 and PGE2 expression of the tumor tissue and the
      peritumoral stroma. Results were correlated with clinical outcome parameters.
      RESULTS: COX-2 and PGE2 were detected in nearly every pulmonary CRC metastasis.
      Staining intensities of pulmonary metastases correlated only weakly with
      intensities found in primary tumors. When dividing metastases in high expressing
      and low expressing tumors, a trend towards longer recurrence free survival and
      improved survival was found in tumors with strong COX-2 and PGE2 staining.
      CONCLUSIONS: In conclusion, this pilot study shows that COX-2 and PGE2 are
      uniformly overexpressed in pulmonary metastases from CRC. High expression of COX
      2 and PGE2 seems to reflect a beneficial tumor biology with late tumor recurrence
      and prolonged overall survival after PM.

PMID- 28449471
TI  - One-year and long-term mortality in patients hospitalized for chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of
      morbidity and mortality worldwide. Identifying potentially-modifiable predictors
      of mortality could help optimize COPD patient management. The aim of this study
      is to determine long-term mortality following hospitalization due to acute
      exacerbations of COPD (AECOPD), as well as AECOPD mortality predictors. METHODS:
      We conducted a retrospective study by reviewing the medical records of all
      patients admitted with AECOPD in the University Hospital Complex of Santiago de
      Compostela in 2007 and 2008. In order to identify variables independently
      associated with mortality, we conducted a multivariate Cox proportional hazard
      regression analysis including those variables which proved to be significant in
      the univariate analysis. RESULTS: Seven hundred and fifty seven patients were
      assessed. Patient mean age was 74.8 years and males accounted for 77% of all
      patients. Mean stay was 12.2 days. Three point six percent of all patients
      required intensive care. As for mortality rates, 1-year mortality was 26.2%, and
      5-year mortality was 64.3%. In both scenarios, the most frequent causes of death
      were respiratory and cardiovascular disorders. Factors independently associated
      with mortality were older age, hospitalization by internal medicine (IMU), length
      of stay, the need for mechanical ventilation (MV) or noninvasive mechanical
      ventilation (NIV), early readmission, and history of atrial fibrillation (AF) and
      dementia. CONCLUSIONS: In patients with COPD, age, exacerbation severity and
      comorbidity have long-term prognostic significance.

PMID- 28449472
TI  - Definitive concurrent chemoradiotherapy with S-1 and cisplatin in elderly
      esophageal squamous cell carcinoma patients.
AB  - BACKGROUND: To evaluate the feasibility and efficiency of definitive concurrent
      chemoradiotherapy (dCRT) with S-1 and cisplatin for elderly esophageal squamous
      cell carcinoma (ESCC) patients. METHODS: Fifty-six elderly patients were included
      from January 2012 to December 2014. Patients received S-1
      (tegafur/gimeracil/oteracil) and cisplatin at doses of 70 mg/m2/day for two weeks
      and 75 mg/m2 on day 1, respectively, every 3 weeks. Radiotherapy was delivered at
      a dose of 180-200 cGy per day to a total dose of 54 Gy. After dCRT, additional
      chemotherapy was administered for two cycles. RESULTS: The median age was 74
      years (range: 70-87 years) and 38 (67.9%) patients were staged with III-IVa.
      Totally, 38 patients completed dCRT as planned. An objective response rate (ORR)
      was seen in 47 (84.0%) patients. The median OS and PFS time were 18.2 and 13.9
      months and the 3-year OS and PFS rates were 30.1% and 14.2%, respectively. The
      most frequent hematological toxicities were leucocytopenia and neutropenia with
      the incidence of 55.4% and 53.6%, respectively. A significantly higher incidence
      of severe leucocytopenia was observed between patients aged >=75 and 70<= age <75
      years. The most common non-hematologic toxicity was esophagitis. CONCLUSIONS:
      dCRT with S-1 and cisplatin yielded satisfactory survival outcomes but treatment
      related toxicities were relatively high, especially for patients aged over 75
      years.

PMID- 28449473
TI  - Anti-PD-1/PD-L1 antibody versus conventional chemotherapy for previously-treated,
      advanced non-small-cell lung cancer: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The anti-PD-1/PD-L1 monoclonal antibody has showed promising results
      in various cancers via enhancing T cell functions. However, many questions remain
      in the role and safety in previously-treated, advanced non-small-cell lung cancer
      (NSCLC). Thus, we conducted a meta-analysis incorporating all available evidences
      to evaluate the efficacy and safety of anti-PD-1/PD-L1 antibody compared with
      chemotherapy. METHODS: PubMed, Web of Science and the Cochrane Library database
      were searched for the studies about the efficacy and safety of anti-PD-1/PD-L1
      antibody in previously-treated, progressive NSCLC patients. Only randomized
      controlled trials (RCTs) comparing anti-PD-1/PD-L1 antibody with conventional
      chemotherapy in NSCLC were included. Overall survival (OS) in the intention-to
      treat population was the primary outcome. The secondary outcomes were:
      progression-free survival (PFS) in the intention-to-treat population, objective
      response rate (ORR), the incidence of adverse events, OS and PFS in different PD
      L1 expression subgroups. RESULTS: Four trials with a total of 2,174 patients were
      included. Anti-PD-1/PD-L1 antibody showed a significant benefit to OS in the
      intention-to-treat population [combined hazard ratio (HR) 0.67; 95% CI: 0.61
      0.75, P<0.00001], a 33% reduction in the relative risk of death. PFS also favored
      anti-PD-1/PD-L1 antibody (HR 0.81, 95% CI: 0.70-0.95, P=0.009). The ORR was
      significantly higher with anti-PD-1/PD-L1 antibody than those with chemotherapy
      (RR of nonresponse, 0.92; 95% CI: 0.89-0.95, P<0.00001). Anti-PD-1/PD-L1 antibody
      was associated with greater efficacy than chemotherapy across the end points of
      OS and PFS when tumor PD-L1 expression scored >=1%, >=5%, and >=50%, except for
      tumor PD-L1 expression scored <1%. The group receiving anti-PD-1/PD-L1 antibody
      had lower rates of treatment-related adverse events of any grade (RR 0.77; 95%
      CI: 0.73-0.81, P<0.00001) and treatment-related adverse events of grade 3-5 (RR
      0.24; 95% CI: 0.14-0.41, P<0.00001). CONCLUSIONS: Anti-PD-1/PD-L1 antibody
      significantly improved survival compared with chemotherapy in previously-treated,
      progressive NSCLC patients. Besides, it also had a better safety profile.

PMID- 28449474
TI  - Impact of lymph node management on resectable non-small cell lung cancer
      patients.
AB  - BACKGROUND: A surgical lung resection with systematic mediastinal lymph node (LN)
      dissection is recommended by the National Comprehensive Cancer Network guideline.
      However, the effective number of dissected LNs, stations and positivity is still
      controversial. The aim of this study is to identify the impact of total numbers,
      LN stations and positivity of dissected LNs on tumor recurrence and overall death
      in resectable non-small cell lung cancer (NSCLC). METHODS: This prognostic study
      used a retrospective data collection design. Adult patients with clinical
      resectable NSCLC who underwent pulmonary resection and mediastinal
      lymphadenectomy at Chiang Mai University between June 2000 and June 2012 were
      enrolled in this study. A multilevel mixed-effects parametric survival model was
      used to identify the effect of numbers, LN stations and positivity of dissected
      LNs to tumor recurrence and mortality. RESULTS: The average number of dissected
      LNs was 22.7+/-12.8. Tumor recurrence was found in 51.3% and overall mortality
      was 43.3%. The number of dissected LNs was a prognostic factor for tumor
      recurrence [HR 0.98, 95% confidence interval (CI): 0.96-0.99]. There was a
      significant difference at the cut-pointed value of 11 dissected LNs for tumor
      recurrence (HR 2.22, 95% CI: 1.26-3.92). Dissection less than 11 nodes and less
      than 5 stations indicated a poor prognostic factor for tumor recurrence: for 3-4
      stations (HR 3.01, 95% CI: 1.22-7.42) and for 1-2 stations (HR 1.96, 95% CI: 1.04
      3.72). The positivity of dissected LNs was also a prognostic factor for tumor
      recurrence and overall mortality (HR 1.01, 95% CI: 1.01-1.02 and HR 1.01, 95% CI:
      1.01-1.03, respectively). CONCLUSIONS: Eleven or more LN dissection with at least
      5 stations influenced recurrent-free survival. Systematic LN dissection (SLND)
      should be performed not only to identify the positivity of dissected LNs but also
      to determine an accurate tumor nodal stage. A larger cohort should be further
      conducted to support these findings.

PMID- 28449475
TI  - A non-randomized retrospective observational study on the subcutaneous esophageal
      reconstruction after esophagectomy: is it feasible in high-risk patients?
AB  - BACKGROUND: Esophageal reconstruction after esophagectomy is a complex procedure
      with high morbidity and mortality. Anastomotic leakage is more severe and
      frequent in patients with preoperative comorbidities and may present with septic
      conditions. Considering the possibility of an easier management of such cases, we
      evaluated the safety and feasibility of subcutaneous esophageal reconstruction in
      patients with high operative risks. METHODS: We performed a non-randomized
      retrospective observational study on the 75 (subcutaneous: 21, intrathoracic: 54)
      esophageal cancer patients who underwent esophageal reconstruction either through
      subcutaneous or intrathoracic route between January 2003 and February 2015.
      Preoperative data including the estimated reasons for the selection of the
      subcutaneous route were obtained from medical charts. Clinical outcomes were
      evaluated and compared between the two groups. RESULTS: The mean postoperative
      hospital stay was longer in the subcutaneous group than the overall group.
      Anastomotic leakage occurred more frequently in the subcutaneous group [10
      (47.6%) vs. 7 (13%), P=0.004]. Three major leakages resulted in chronic cutaneous
      fistula, but were successfully treated by lower neck reconstruction using radial
      forearm fasciocutaneous free flap (RFFF). There was no in-hospital mortality in
      the subcutaneous group. CONCLUSIONS: Subcutaneous esophageal reconstruction in
      high-risk patients showed a higher rate of anastomotic leakage. However, easier
      correction without fatal septic conditions could be obtained by primary repair or
      flap reconstruction resulting in lower perioperative mortality. Therefore,
      esophageal reconstruction through the subcutaneous route is not recommended as a
      routine primary option. However, in highly selected patients with unfavorable
      preoperative comorbidities or intraoperative findings, especially those with poor
      blood supply to the graft, graft hematoma or edema, or gross tumor invasion to
      surrounding tissues, esophageal reconstruction through the subcutaneous route may
      carefully be considered as an alternative to the conventional surgical
      techniques.

PMID- 28449476
TI  - Prognostic impact of M descriptors of the 8th edition of TNM classification of
      lung cancer.
AB  - BACKGROUND: The 8th edition of the tumor, node and metastasis (TNM)
      classification of lung cancer will be enacted in January 2017. The aim of this
      study was to analyze the survival differences among the three new categories of
      metastatic disease: intrathoracic metastasis (M1a), single extrathoracic
      metastasis (M1b) and multiple extrathoracic metastases (M1c) in our cohort of
      patients with non-small cell lung cancer (NSCLC). METHODS: This is a
      retrospective single-center study including NSCLC patients with metastatic
      disease at diagnosis. Patients were divided into three groups (M1a, M1b, M1c).
      Overall survival (OS) within and between these subgroups was calculated using the
      Kaplan-Meier method. RESULTS: A total of 288 patients were included (112 M1a, 28
      M1b and 148 M1c). Median OS of M1c was significantly worse than M1a or M1b tumors
      (P<0.001). No significant differences were found among the M1a descriptors
      (pleural/pericardial nodules/effusion, bilateral tumor nodules or both
      descriptors) (P=0.722) and between M1a and M1b tumors (P=0.517). OS of patients
      with one metastasis in a single organ was not significantly different from OS of
      patients with two metastases in a single organ (P=0.180). Among M1c tumors, OS
      was significantly better in patients with multiple metastases in a single organ
      than in patients with multiple metastases in multiple organs (P=0.001).
      CONCLUSIONS: Our results support the proposal to keep the M1a category unchanged
      in the 8th edition as well as the proposed restructuring of the M1b in the new
      M1b and M1c categories. However, our results raise questions about the definition
      of oligometastatic disease and, consequently, the criteria of M1b and M1c
      category.

PMID- 28449477
TI  - Continuous administration of recombinant human B-type natriuretic peptide can
      improve heart and renal function in patients after cardiopulmonary bypass
      surgery.
AB  - BACKGROUND: Any cardiac surgery under cardiopulmonary bypass (CPB) will induce
      ischemia-reperfusion injury and systematic inflammatory response, which may lead
      to exacerbation. Conventional therapy strategy is to use inotropes, diuretics and
      vasodilator drugs, yet, the therapeutic effects of which need to be improved.
      Recombinant human B-type natriuretic peptide (rhBNP) has been shown to be
      efficacious in the treatment of acute decompensated heart failure and acute
      myocardial infarction. However, the effects of rhBNP on patients carried out CPB
      surgery is unknown. METHODS: We retrospect 357 patients carried out CPB surgery
      between Jan 1st 2014 and Dec 31st 2015 of our department. And according the use
      of rhBNP, these patients were divided into two groups: rhBNP group and control
      group. Patients in rhBNP group were received continuous intravenous rhBNP (0.0075
      0.01 ug/kg/min) in 6 hours after CPB surgery, for a period of 72 h. Hemodynamic
      parameters were measured immediately after CPB surgery, and then at 2, 4, 8, 12
      and 24 h after surgery. Blood samples were obtained immediately after surgery and
      thereafter once a day at 6:00 AM within the first 3 days after surgery. The daily
      urine volume as well as the time of tracheal intubation, ICU stay and chest
      drainage were also recorded. RESULTS: The baseline characteristics and heart
      functions were well balanced between two groups, and no patient died in the
      surgery. It showed significant differences in time-dependent changes in both
      groups of MAP (P<0.0001, within groups), MPAP (P<0.0001, within groups), PAWP
      (P<0.0001, within groups), CI (P<0.0001, within groups), SVRI (P<0.0001, within
      groups), serum BNP (P<0.0001, within groups), CK-MB (P<0.0001, within groups),
      troponin (P<0.0001, within groups) and creatinine (P<0.0001, within groups). It
      also showed significant differences in time-dependent changes between the two
      groups of MAP (P=0.04, between groups), PAWP (P=0.04, between groups), serum
      troponin (P<0.0001, between groups), serum creatinine (P<0.0001, between groups)
      and urine volume (P<0.0001, between groups). Interestingly, our results showed
      that patients in rhBNP group tended to wean off the respirator half a day later
      than those in control group (P=0.05), while no significant difference showed in
      both the length of chest drainage time and intensive care unit stay between the
      two groups. CONCLUSIONS: The administration of rhBNP can improve heart and renal
      function in patients underwent CPB surgery as well as accelerating the recovery
      from myocardial injury. But the prognosis of the patients who were administrated
      rhBNP did not improve in our study.

PMID- 28449478
TI  - Protective effect of propofol preconditioning on ischemia-reperfusion injury in
      human hepatocyte.
AB  - BACKGROUND: Blood reperfusion after ischemia is the main measure to restore cell
      function. This study was aimed to explore the effect of propofol on rat and cell
      models of liver ischemia-reperfusion (I/R) injury, and to investigate its
      possible mechanism. METHODS: Wistar rats were divided into four groups: control
      group, sham group, I/R group, and propofol group. Human hepatocyte HL7702 was
      divided into six groups: control group, I/R group and propofol (5, 10, 20 and 40
      umol/L) groups. After the animal and cell models were established, the alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA)
      and adenosine triphosphate (ATP) levels in liver tissues and hepatocytes were
      measured. Cell viability and apoptosis of hepatocytes were respectively
      determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      and flow cytometry. Furthermore, the expressions of apoptosis-related proteins in
      hepatocytes were determined by Western blot analysis. RESULTS: ALT, AST and MDA
      levels were all decreased significantly, and the ATP level was increased
      significantly in propofol group compared with that in I/R group in both liver
      tissues and hepatocytes. Additionally, cell viability of hepatocytes in propofol
      group was higher than that in I/R group, while the percentage of apoptotic cells
      in propofol group was less than that in I/R group. Moreover, the expression of
      caspase-3 decreased and the expression of Bcl-2 increased significantly after
      propofol preconditioning. CONCLUSIONS: Our findings suggested that propofol
      preconditioning might be an effective strategy for protecting the liver from I/R
      injury, which might provide a scientific basis for clinical application.

PMID- 28449479
TI  - Early results of the Sorin(r) Perceval S sutureless valve: systematic review and
      meta-analysis.
AB  - BACKGROUND: Minimally invasive aortic valve replacement (MAVR) has demonstrated a
      benefit with respect to increased patient satisfaction due to minimised pain and
      earlier recovery. Sutureless valves may benefit MAVR and conventional aortic
      valve replacement (AVR) by reducing operative times and blood transfusion
      requirements. The Perceval valve (Sorin, Salluggia, Italy) is a self-expanding
      prosthesis made from bovine pericardium mounted in a nitinol stent, designed to
      simplify the implantation of an aortic valve. This meta-analysis evaluates the
      clinical, haemodynamic, and survival outcomes of the Perceval sutureless valve.
      METHODS: An electronic search of 4 databases was performed from January 2000 to
      December 2016. Primary outcomes included mortality and stroke. Secondary outcomes
      included minimally invasive access, paravalvular leak, overall long-term
      survival, postoperative echocardiographic findings, and functional class
      improvement. RESULTS: After the application of inclusion and exclusion criteria,
      14 of 66 relevant articles were selected for assessment. Of these 14 studies, a
      total number of 2,505 patients were included. The current evidence on the
      Perceval valve for aortic valve disease is limited to observational studies only.
      Minimally invasive surgery was performed in 976 patients, of which 336 were via
      the right anterior thoracotomy approach. The Perceval M and L sutureless valves
      were the most frequently used, 782 and 770 respectively. The incidence of major
      adverse events included 30-day mortality (0 to 4.9%), cerebrovascular accident (0
      to 3%), permanent pacemaker insertion (0 to 17%), moderate to severe paravalvular
      leak (0 to 8.6%), and re-operation (0 to 4.8%). Post-operative mean aortic valve
      gradient ranged from 9 to 15.9 mmHg and post-operative New York Heart Association
      (NYHA) Class I or II ranged from 82% to 96%. The 1-year survival ranged from 86%
      to 100%; and 5-year survival was 71.3% to 85.5% in two studies. CONCLUSIONS: The
      Perceval valve is associated with excellent post-operative results in MAVR and in
      conventional AVR. Larger randomised controlled studies are required to evaluate
      the long-term efficacy of the prosthesis.

PMID- 28449480
TI  - Reconstruction of mediastinal vessels for invasive thymoma: a retrospective
      analysis of 25 cases.
AB  - BACKGROUND: Discuss an appropriate strategy for treatment of invasive thymoma
      invading adjacent great vessels. METHODS: A retrospective study on 25 patients
      with invasive thymoma invading neighboring great vessels was performed. The
      corresponding data including clinical presentation, operation procedure, adjuvant
      radio-chemotherapy and follow-up were reviewed. RESULTS: Twenty of 25 (80%)
      patients with invasive thymoma underwent complete resection of the tumor along
      with vessel reconstruction. Intraoperatively, different types of operation were
      conducted, namely, brachiocephalic vein (BCV)-right atrial appendage (RAA)
      reconstruction in 11 cases, complex vessel reconstruction (more than one graft)
      in 1 case and superior vena cava (SVC)-SVC reconstruction in the remaining cases.
      Ringed polytetrafluoroethylene (PTFE) grafts were used for vessel reconstruction.
      Postoperatively, three cases suffered from pulmonary infection, and three cases
      had haemothorax, chylothorax and atelectasis, respectively. Two patients died due
      to acute respiratory distress syndrome within 90 days after the surgery. Within
      the remaining patients, 11 cases (44%) experienced a relapse and finally 8 (32%)
      patients died. Compared to R1 resection group, R0 resection group had a better
      prognosis (Log-rank P=0.0196). The 3- and 5-year survival rates were 79.6% and
      59.1%, with median survival time of 84 months. CONCLUSIONS: Reconstruction of
      mediastinal vessels for invasive thymoma is a feasible technology method. Radical
      resection of the tumor with involved neighboring structures is the key to prolong
      overall survival for patients suffered from invasive thymoma.

PMID- 28449481
TI  - Procalcitonin as preoperative marker for surgery in advanced parapneumonic
      empyema.
AB  - BACKGROUND: The optimal time point for surgical management of advanced
      parapneumonic empyema in need of open pleurectomy and decortication remains
      unclear. We hypothesized that surgical outcomes will be better when procalcitonin
      (PCT) levels have dropped to normal ranges as evidence for resolution of the
      underlying pneumonia. METHODS: We retrospectively analyzed outcomes of 38
      patients with advanced parapneumonic empyema who underwent open decortication and
      pleurectomy with available preoperative PCT (pPCT) values. Patients were divided
      into two groups based on the pPCT cut-off of 0.25 ug/L. Total length of stay was
      the primary endpoint. Secondary endpoints included postoperative length of stay,
      surgery-related complications and death. RESULTS: Patients with a pPCT >=0.25
      ug/L had a significantly longer total length of stay compared to patients with a
      pPCT level <0.25 ug/L [mean 22.4 vs. 15.0 days, difference -7.4 days (95% CI: 
      12.8 to -2.0), P=0.009]. This was also confirmed in linear regression analysis
      adjusting for age, gender and comorbidities [adjusted regression coefficient for
      log-transformed length of stay -0.27, 95% CI: -0.02 to -0.52, P=0.037]. Results
      for postoperative length of stay were similar. Eight patients in the pPCT >=0.25
      ug/L group had postoperative complications with two deaths while no complications
      occurred in the PCT <0.25 ug/L group (38% vs. 0%, P=0.004). CONCLUSIONS: These
      data suggest better surgical outcomes in advanced parapneumonic empyema when
      pneumonia has resolved with a pPCT drop of <0.25 ug/L. A larger, prospective
      study is needed to confirm these results.

PMID- 28449482
TI  - Retrospective analysis of stereotactic ablative radiotherapy (SABR) for
      metastatic lung lesions (MLLs) in comparison with a contemporaneous cohort of
      primary lung lesions (PLLs).
AB  - BACKGROUND: The net benefit from local ablative therapy for pulmonary
      oligometastases remains unknown. The outcomes of stereotactic ablative
      radiotherapy (SABR) for metastatic lung lesions (MLLs) were analyzed
      retrospectively and compared with those of SABR for primary lung lesions (PLLs).
      METHODS: Medical records of patients treated with lung SABR between 2011 and 2014
      were retrospectively reviewed. Basic patient, lesion and treatment
      characteristics were compared using the Pearson chi-square test for categorical
      and Mann-Whitney U test for continuous variables. To estimate the rates of local
      control (LC), progression-free survival (PFS), survival after the first
      progression post-SABR (SAPF) and overall survival (OS), the Kaplan-Meier method
      was used, and the differences between groups were assessed by means of the log
      rank test. The uni- and multivariate Cox proportional hazards regression model
      was used to identify predictive factors for these endpoints. RESULTS: Twenty-nine
      MLLs in 18 consecutive patients and 51 PLLs in 42 patients were treated
      stereotactically and included in the study. Median follow-up was 14 months
      (range, 4-40 months). Although patients with MLLs had a significantly better
      cardiopulmonary function (P=0.0001), more conservative dose-fractionation
      schedules were prescribed (P=0.0001), but this did not result in a significant
      difference in LC (P=0.98), PFS (P=0.06) and OS (P=0.14). Multivariate analysis
      revealed that the dose per fraction (>= or <12 Gy) was an independent predictor
      for LC (P=0.02) and PFS (P=0.01) for the whole population, and for PFS (P=0.02)
      in the PLLs group. Late toxicities >= G2 occurred in six patients with PLLs,
      compared with none in the metastatic group. CONCLUSIONS: SABR for MLLs was as
      successful as for PLLs with respect to LC and OS with lower long-term toxicity in
      patients with MLLs. Dose per fraction >=12 Gy turned out to be an independent,
      favorable prognostic factor.

PMID- 28449483
TI  - Epicardial left atrial appendage closure-comparison of surgical techniques in an
      ex vivo model.
AB  - BACKGROUND: Formation of clots in the left atrial appendage (LAA) may lead to
      embolism and consecutive cerebral stroke. This risk is reduced by closure and
      resection. To address the efficacy of surgical LAA closure, resilience to
      pneumatic pressure was studied. Different surgical techniques were compared in an
      experimental model. METHODS: From freshly slaughtered pigs cardiopulmonary
      preparations were taken. The left atrium was clamped airtight and the LAA was
      cannulated. Via a manually operated pump pressure was applied and a digital
      pressure gauge was connected. Four groups (each n=12) with different epicardial
      closures were studied: (I) purse string; (II) single layered continuous suture;
      (III) double layered suture; (IV) surgical stapler. A nonparametric test was used
      for group comparisons of mean burst pressures (mmHg). Statistical significance
      was defined at P<0.05. RESULTS: Mean burst pressures in group 1 amounted to
      97.1+/-13.0 mmHg, in group 2 to 105.5+/-13.3 mmHg, in group 3 to 124.6+/-14.2
      mmHg and in group 4 to 136.6+/-12.5 mmHg. Excepting differences between groups 1
      and 2 comparisons between groups were significantly different. CONCLUSIONS: In an
      ex vivo model surgical staplers and double layered hand crafted sutures proved
      well suitable for closure of the LAA. They were significantly superior to single
      layered sutures in terms of resilience to pneumatic pressure. This may be
      relevant to durability and should be discussed with regard to clinical choice.

PMID- 28449484
TI  - Clinical presentation and characteristics of 25 adult cases of pulmonary
      sequestration.
AB  - BACKGROUND: Pulmonary sequestration (PS) is a rare congenital abnormality of lung
      tissue. Only few series of adult cases are reported. The aim was to describe
      clinical characteristics in adult cases of PS and to compare outcomes in
      different clinical situations. METHODS: Using MSD engine we searched for cases of
      PS that have been diagnosed between Jan 1st, 2005 and Dec 31st, 2015. Clinical
      data was retrospectively gathered. Statistica v.12 (StatSoft, Inc.) was used for
      statistical analyses. RESULTS: We found 25 cases (18 females, 7 males), which
      underwent surgery and were histologically proven. There were 22 cases of
      intralobar PS. 7 cases were asymptomatic, 12 had infectious history (including 3
      cases of lung abscess and pleural empyema), 4 presented with hemoptysis, 2 with
      chest pain. The average age to undergo surgery was 38.24, in the asymptomatic
      group 34, in symptomatic 39.89. In the latter the symptoms preceded the surgery
      for 2.45-year. Great majority of sequestrations was located in lower lobes (96%),
      52% on the left. Symptomatic cases were at higher than expected risk of surgical
      complications, comparing to asymptomatic (chi2, P=0.04). In most cases there were
      surgical and histological signs of infection, only in 9 cases etiological factor
      was determined: in 5 cases it was A. fumigatus. A 0.53-day longer post-surgical
      hospital stay was observed in the symptomatic group, no statistical significance
      was found (U-test, P=0.45). CONCLUSIONS: Surgical treatment of symptomatic cases
      of PS is characterized by slightly longer post-surgical hospital stay and higher
      risk of surgical complications. Fungal infections are the most likely to occur in
      PS.

PMID- 28449485
TI  - Prognostic effects of preoperative obstructive pneumonitis or atelectasis and
      comparison with tumor size in non-small cell lung cancer.
AB  - BACKGROUND: In the eighth TNM staging system proposal, lung cancer with part or
      complete obstructive pneumonitis/atelectasis was classified to T2 category, and
      dividing lines of T category were changed. We conducted this study to search
      prognostic effect of preoperative obstructive pneumonitis/atelectasis and its
      comparison with tumor size. METHODS: We collected clinical characteristics,
      preoperative hematological indicators, follow-up information of 1,313 lung cancer
      patients. Chi-square test was used to search relationship between obstruction
      pneumonitis/atelectasis and other factors. Kaplan-Meier (K-M) curves and cox
      regression methods were used for survival analysis. RESULTS: Preoperative
      obstructive pneumonitis/atelectasis indicated shorter OS (HR: 1.308; 95% CI:
      1.058-1.619) and RFS (HR: 1.276; 95% CI: 1.032-1.579) as an independent factor.
      In comparison with tumor size, we found patients with obstructive
      pneumonitis/atelectasis and T1 size tumor had similar prognosis to those with T2
      size but without obstructive pneumonitis/atelectasis, and OS, RFS of patients
      with obstructive pneumonitis/atelectasis and T2 size were significantly shorter
      than those with T2 tumor size but without obstructive pneumonitis/atelectasis,
      while similar to patients with T3 tumor size but without obstructive
      pneumonitis/atelectasis according to division by the eighth edition. We also
      found obstructive pneumonitis/atelectasis was significantly related to higher
      neutrophil (P<0.001), platelet (P<0.001), monocyte (P<0.001), NLR (P<0.001), PLR
      (P=0.002), ESR (P<0.001) and lower LMR (P<0.001). CONCLUSIONS: Preoperative
      obstructive pneumonitis/atelectasis predicted poor survival independently in non
      small cell lung cancer (NSCLC). And we suggested which T staging group the
      patients with obstructive pneumonitis/atelectasis would be divided to should
      depend on tumor size in the eighth TNM staging system.

PMID- 28449486
TI  - The prevalence of pulmonary hypertension in patients with obesity hypoventilation
      syndrome: a prospective observational study.
AB  - BACKGROUND: One important cardiovascular morbidity that is associated with
      obesity hypoventilation syndrome (OHS) is the development of pulmonary
      hypertension (PH). However, few studies have assessed PH in OHS patients.
      Therefore, we prospectively assessed the prevalence of PH in a large sample of
      OHS patients. METHODS: In this prospective observational study, all consecutive
      OHS patients referred to the sleep disorders clinic during the study period were
      included. All patients underwent overnight polysomnography (PSG), spirometry,
      arterial blood samples and thyroid tests. Transthoracic echocardiography was
      performed for patients who agreed to participate in the study. PH was defined as
      systolic pulmonary artery pressure (SPAP) >40 mmHg. RESULTS: Echocardiographic
      data were available for 77 patients with a mean age of 60.5+/-11.7 years, a BMI
      of 43.2+/-10.4 kg/m2, and an Epworth Sleepiness Scale (ESS) score of 11.4+/-5.5.
      SPAP was >40 mmHg in 53 patients (68.8%), with a mean SPAP of 64.1+/-17.1 mmHg.
      There were no differences between the OHS patients with PH and those with normal
      PAP in terms of age, BMI, presenting symptoms, comorbidities, arterial blood
      gasses (ABG), and spirometric and PSG parameters. Approximately 71.4% of women
      and 61.9% of men with OHS also had PH. SPAP was >40-55 mmHg in 19 (24.7%)
      patients (18 women), >55-70 mmHg in 15 (19.5%) patients (6 women) and >70 mmHg in
      19 (24.7%) patients (16 women). Severe PH (SPAP >70 mmHg) was diagnosed in 28.6%
      of the women and 14.3% of the men. CONCLUSIONS: PH is very common among patients
      with OHS who have been referred to sleep disorders clinics. PH should be
      considered in the regular clinical assessment of all patients with OHS.

PMID- 28449487
TI  - Performance in the shuttle walk test is associated with cardiopulmonary
      complications after lung resections.
AB  - BACKGROUND: The current functional guidelines recommend the shuttle walk test
      (SWT) as an initial screening tool to identify candidates for lung resection
      without requiring cardiopulmonary exercise testing. This study aims to: (I)
      assess the use of the SWT in predicting postoperative cardiopulmonary
      complications; and (II) determine whether the recommended 400 m cut-off is an
      appropriate distance. METHODS: We retrospectively analysed 101 patients that had
      performed a SWT prior to surgery. Univariate and multivariate regression analyses
      were used to test associations between patient variables [demographics, pre
      existing conditions, pulmonary function, oxygen desaturation during the SWT,
      shuttle walk distance (SWD)] and post-operative cardiopulmonary complications.
      RESULTS: Patients without cardiopulmonary complications walked longer distance
      compared to those with complication (417.3 vs. 348.6 m, P=0.01. Fifty two
      patients walked less than 400 m and 16 less than 250 m. Only 10% of patients who
      walked at least 400 m had cardiopulmonary complications compared to 33% of those
      who did not reach this distance (P=0.008). Half of the patients who walked less
      than 400 m and desaturated during the exercise developed cardiopulmonary
      complications. A SWD shorter than 400 m remained the only factor significantly
      associated with cardiopulmonary complications (P=0.009, OR: 4.3) after logistic
      regression analysis. CONCLUSIONS: Our results support the use of the SWT as an
      initial screening tool in all patients prior to lung resection. Patients walking
      longer than 400 m experienced very low incidence of complications and would not
      need further testing prior to proceed to lung resection.

PMID- 28449488
TI  - Clinicopathological features of Chinese lung cancer patients with epidermal
      growth factor receptor mutation.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) gene was the major causative
      gene of lung cancer and also the specific treatment target. It is necessary to
      analyze the genotype and phenotype characters of patients. METHODS: We
      investigated 1,034 lung cancer patients in this study. The collected
      clinicopathological parameters included gender, age at diagnosis, smoking status,
      pathological TNM stage, tumor morphology and location, visceral pleural invasion
      as well as histological type. RESULTS: Almost 50% participants had EGFR
      mutations. L858R in exon 21 was the most common type. Concomitant mutation, 19
      del and L858R, were detected in 20 patients. Compared to patients with exon 19
      del or L858R mutations solely, they were inclined to have small size
      adenocarcinomas which occurred in bilateral and invaded the visceral pleura. The
      tyrosine kinases inhibitors (TKIs)-resistant mutation, insertions in exon 20, was
      detected in 11 patients. CONCLUSIONS: The summarized clinicopathological features
      will help clinicians to implement the feasible treatment plan.

PMID- 28449489
TI  - Electromagnetic navigational bronchoscopy with dye marking for identification of
      small peripheral lung nodules during minimally invasive surgical resection.
AB  - BACKGROUND: Identification of small peripheral lung nodules during minimally
      invasive resection can be challenging. Electromagnetic navigational bronchoscopy
      (ENB) with injection of dye to identify nodules can be performed by the surgeon
      immediately prior to resection. We evaluated the effectiveness of ENB with dye
      marking to aid minimally invasive resection. METHODS: Patients with peripheral
      pulmonary nodules underwent ENB before planned thoracoscopic or robotic-assisted
      thoracoscopic resection. Methylene blue was injected directly into the lesion for
      pleural-based lesions or peripherally for lesions deep to the pleural surface.
      Surgical resection was then immediately performed. Technical success was defined
      as identification of the dye marking within/close to the lesion with pathological
      confirmation after minimally invasive surgical resection. RESULTS: Seventeen
      patients (19 nodules) underwent ENB with dye marking followed by minimally
      invasive resection. Median lesion size was 9 mm (4-32 mm) and the median distance
      from the pleura was 9.5 mm (1-40 mm). Overall success rate was 79% (15/19). In
      two cases the dye was not visualized and in the remaining two there was
      extravasation of dye into the pleural space. There were trends favoring technical
      success for nodules that were larger or closer to the pleural surface. Five
      patients required adhesiolysis to visualize the target lesion and all were
      successful. There were no significant adverse events and a definitive diagnosis
      was ultimately accomplished in all patients. CONCLUSIONS: ENB with dye marking is
      useful for guiding minimally invasive resection of small peripheral lung nodules.
      ENB can be undertaken immediately before performing resection in the operating
      room. This improves workflow and avoids the need for a separate localization
      procedure.

PMID- 28449490
TI  - Transcutaneous electrical acupoint stimulation (TEAS) ameliorates chemotherapy
      induced bone marrow suppression in lung cancer patients.
AB  - BACKGROUND: To investigate the effect of percutaneous electrical stimulation on
      chemotherapy-induced bone marrow suppression in patients with lung cancer.
      METHODS: From December 2014 to August 2015, one hundred ninety-one non-small cell
      lung cancer patients with chemotherapy naive were randomly divided into control
      group, medication group, and transcutaneous electrical acupoint stimulation
      (TEAS) group. Patients with the control group received routine nursing care, the
      medication group was treated by oral administration of prophylactic agents, and
      TEAS group received electrical stimulation of acupoints including Dazhui (DU14),
      Geshu (BL17), Zusanli (ST36), Sanyinjiao (SP6), and Hegu (LI4). The primary end
      point was the blood routine indexes and secondary end point was the degree of
      comfort. RESULTS: The white blood cell in the TEAS group was significantly higher
      than the control group on day 8 and day 14 (P<0.05). The platelet count in the
      TEAS group was significantly higher than control group on day 5, day 8 and day 11
      (P<0.05). The comfort score in the TEAS group was significantly higher than
      control group on day 8 (P<0.05). CONCLUSIONS: Percutaneous electrical stimulation
      of acupoints could prevent chemotherapy-induced bone marrow suppression in lung
      cancer patients and ensure a smooth continuation of chemotherapy.

PMID- 28449491
TI  - Characteristics and provision of care of patients with the acute respiratory
      distress syndrome: descriptive findings from the DACAPO cohort baseline and
      comparison with international findings.
AB  - BACKGROUND: Little is known about the characteristics and real world life
      circumstances of ARDS (acute respiratory distress syndrome) patient populations.
      This knowledge is essential for transferring evidence-based therapy into routine
      healthcare. The aim of this study was to report socio-demographic and clinical
      characteristics in an unselected population of ARDS patients and to compare these
      results to findings from other large ARDS cohorts. METHODS: A German based cross
      sectional observational study was carried out. A total of 700 ARDS patients were
      recruited in 59 study sites between September 2014 and January 2016. Socio
      demographic, disease and care related variables were recorded. Additionally,
      characteristics of other large ARDS cohorts identified by a systematic literature
      search were extracted into evidence tables. RESULTS: Median age of ARDS patients
      was 58 years, 69% were male. Sixty percent had no employment, predominantly due
      to retirement. Seventy-one percent lived with a partner. The main cause of ARDS
      was a pulmonary 'direct' origin (79%). The distribution of severity was as
      follows: mild (14%), moderate (48%), severe (38%). Overall ICU mortality was
      calculated to be 34%. The observed prevalence of critical events (hypoxemia,
      hypoglycemia, re-intubation) was 47%. Supportive measures during ICU-treatment
      were applied to 60% of the patients. Other ARDS cohorts revealed a high
      heterogeneity in reported concomitant diseases, but sepsis and pneumonia were
      most frequently reported. Mean age ranged from 54 to 71 years and most patients
      were male. Other socio-demographic factors have been almost neglected.
      CONCLUSIONS: The proportion of patients suffering of mild ARDS was lower compared
      to the only study identified, which also applied the Berlin definition. The
      frequency of critical events during ICU treatment was high and the implementation
      of evidence-based therapy (prone positioning, neuro-muscular blockers) was
      limited. More evidence on socio-demographic characteristics and further studies
      applying the current diagnostic criteria are desirable.

PMID- 28449492
TI  - Somatic cough syndrome or psychogenic cough-what is the difference?
AB  - The term psychogenic cough has been used to describe cough without obvious
      medical etiology, which is refractory to medical management and considered to
      have a psychiatric or psychological basis. However there are limitations in the
      research into psychogenic cough with limited empirical data on how to define the
      condition or differentially diagnose it from other forms of chronic cough. The
      term somatic cough syndrome was introduced by the American College of Chest
      physicians in 2015 during their revision of the 2006 guideline on psychogenic
      cough. Psychomorbidity can be present in chronic cough arising from a variety of
      etiologies and can impact on symptom perception and clinical management of the
      condition. Psychological symptoms can also improve after effective treatment of
      the chronic cough. The recently published American College of Chest Physicians
      cough guidelines recommended replacing the term psychogenic cough with the term
      somatic cough syndrome in order to be consistent with the Diagnostic Statistical
      Manual of Mental Disorders, 5th edition (DSM-5) where the term psychogenic is no
      longer used. This paper outlines the current evidence regarding psychogenic
      cough, proposes a model for conceptualising psychological issues in chronic cough
      and discusses strategies for clinical management of psychological issues in
      patients with chronic cough.

PMID- 28449493
TI  - TRPV1 polymorphisms influence capsaicin cough sensitivity in men.

PMID- 28449494
TI  - Clinical outcomes for multi- and extensively drug resistant tuberculosis patients
      with adjunctive resectional lung surgery in Beijing, China.
AB  - The objective of this study was to assess the performance of adjective
      resectional lung surgery for multidrug resistant (MDR-) and extensively drug
      resistant tuberculosis (XDR-TB) patients in Beijing, China. Between October 1992
      and October 2012, 21 MDR/XDR patients undergoing pulmonary resection at Beijing
      Chest Hospital were enrolled in this study. The clinical outcomes of MDR- and XDR
      TB patients were analyzed with a 3-year surgical follow-up. Out of 21 patients
      enrolled in this study, 20 patients (95.2%) had unilateral cavitary disease, and
      1 patient (4.8%) exhibited bilateral cavitary disease. The most frequent
      cavitation was located in the left upper lung (38.1%, 8/21). In addition, 19
      (90.5%) underwent lobectomy, and the other two (9.5%) underwent pneumonectomy due
      to obvious cavitation in both upper and lower fields of unilateral lung. After 3
      year follow-up, eight patients (38.1%) were cured and 13 patients (61.9%)
      suffered from unfavorable outcomes. Of 13 patients with unfavorable outcomes, 5
      patients (38.5%) died of further progression of TB disease, and 8 patients
      (61.5%) relapsed. Only 1 (14.3%) out of 7 XDR-TB patients was cured, compared
      with 7 (50.0%) out of 14 multidrug-resistant tuberculosis (MDR-TB) patients. In
      conclusion, our data demonstrate that if available, surgical treatment should be
      considered in MDR/XDR-TB patients in China. The subsequent treatment with second
      line drugs may play the most important role in determining the final clinical
      outcome for MDR/XDR-TB patients.

PMID- 28449495
TI  - Laser resection of pulmonary nodule via uniportal thoracoscopic surgery.
AB  - Uniportal video-assisted thoracic surgery (VATS) lung wedge resection usually
      requires three devices, thoracoscope, lung retracting instrument and an endo
      stapler cutter to perform the procedure. With advances in miniaturization of the
      thoracoscope and lung retracting instruments, a major limitation to operating
      through a smaller uniportal incision has become the endo-stapler. We describe the
      surgical technique for uniportal VATS laser lung resection which uses a much
      narrower laser catheter device to replace the endo-stapler for resection. The new
      approach to limited lung resection can potentially reduce instrument fencing and
      the uniportal incision wound size, while achieving satisfactory hemostasis and
      pneumostasis.

PMID- 28449496
TI  - The mechanisms of radioresistance in esophageal squamous cell carcinoma and
      current strategies in radiosensitivity.
AB  - Esophageal cancer is the eighth most common cancer and the sixth leading cause of
      cancer-related death worldwide. Surgery is the primary form of treatment, but the
      survival is poor, especially for patients with locally advanced esophageal
      cancer. Radiotherapy has been a critical treatment option that may be combined
      with chemotherapy in patients with unresectable esophageal cancer. However,
      resistance to chemoradiotherapy might result in treatment failures and cancer
      relapse. This review will mainly focus on the possible cellular mechanisms and
      tumor-associated microenvironmental (TAM) factors that result in radioresistance
      in patients with esophageal cancer. In addition, current strategies to increase
      radiosensitivity, including targeted therapy and the use of radiosensitive
      biomarkers in clinical treatment, are discussed in this review.

PMID- 28449498
TI  - Trans-tracheostomy repair of tracheo-esophageal fistula under endoscopic view in
      a 75-year-old woman.
AB  - Tracheo-esophageal fistula is a life-threatening condition for fatal pulmonary
      complications. Surgery is the treatment of choice. Unfortunately, the most of
      patients are unfit for surgery and in these cases there is no a standardized
      management. Herein, we reported a clinical case of a 75-year-old-woman with a
      tracheoesophageal fistula related to tracheostomy. The fistula was localized 3.5
      cm below the vocal folds and extended 3 cm distally. The patient's poor clinical
      condition contraindicated surgery while the characteristics of fistula prevented
      any successfully endoscopic repair with standard methods as application of fibrin
      glue, clipping, or stenting. Thus, we performed a minimally invasive procedure as
      trans-tracheotomy closure of the fistula under endoscopic view. Under general
      anesthesia, the patient was intubated with a rigid bronchoscopy. The cannula was
      removed and a standard needle-holder was inserted through the tracheotomy. The
      tear was closed from the distal to the proximal ends with interrupted stitch.
      Following, a Montgomery T tube was inserted to protect the suture and maintain
      the air-way patency. At the last follow-up (7 months after the procedure), the
      patient was alive and tolerated a full diet.

PMID- 28449497
TI  - Retrosternal goitre: the role of the thoracic surgeon.
AB  - Purpose of this Mini-Review is to evaluate the role of a thoracic surgeon in the
      surgical management of retrosternal goitre. A cervical approach is sufficient in
      the majority of the cases. On the other hand, there are cases where a cervical
      approach is combined with sternotomy or thoracotomy, depending on the position of
      the goitre, in the anterior or posterior mediastinum. On top of that, different
      minimally invasive approaches including video-assisted thoracoscopic surgery
      (VATS) and robotic-assisted surgery (RATS) have been introduced, providing faster
      recovery, superior manoeuvrability and better aesthetic results.

PMID- 28449499
TI  - Regional dietary characteristics and bronchial foreign body: a repeated
      misdiagnosis caused by a red pepper.
AB  - Bronchial foreign body is a common health problem worldwide, types of bronchial
      foreign bodies are variegated, depending on patient age and cultural background
      including religious beliefs as well as alimentary habits. However, misdiagnoses
      caused by regional dietary correlation factors were rarely concerned. In this
      case, a 52-year-old woman with aggravated cough and hemosputum took thoracic CT
      scan twice and flexible fiberoptic bronchoscopy 5 times, which all revealed the
      chronic pulmonary inflammation. Furthermore, the biopsies showed bronchial
      granulation nodule formation. With the highly suspicion of tumor, lung lobe
      resection was conducted. However, from the resected specimen, we belatedly found
      a red pepper inserted in the bronchus, without tumor cell in postoperative
      pathological analysis. We reviewed the case, analyzed the potential factors that
      may led to repeated misdiagnoses, and concluded that regional dietary
      characteristics and higher clinical suspicion should be seriously under
      consideration in the process of diagnosis.

PMID- 28449500
TI  - Resectable primary pleural myxoid liposarcoma with a pedicle: report of a rare
      case and literature review.
AB  - Primary pleural myxoid liposarcoma is a rare tumor. Here, we report a primary
      myxoid liposarcoma occupying the majority of the left thoracic cavity with
      features suggesting invasion. Computed tomography (CT) at medical check-up
      incidentally revealed a bulky inhomogeneous fatty mass. The tumor's large size
      made a prediction of its resectability by preoperative CT difficult. The patient
      underwent an operation, which revealed that the tumor was attached to the pleura
      with a thin pedicle; the tumor was resected completely. Few therapies for pleural
      liposarcoma other than resection are available; hence, surgery should be
      considered even if the tumor's size implies invasion on radiological imaging. In
      this case report, we discuss the imaging findings of this case with a review of
      the related literature.

PMID- 28449502
TI  - Bronchopulmonary carcinoid with a single lymph node metastasis causing ectopic
      Cushing's syndrome.
AB  - Bronchial carcinoid tumors (BCTs) represent a subgroup of bronchopulmonary
      neuroendocrine tumors which have the ability to produce neuropeptides. Merely 2%
      of BCTs secrete ACTH and less than 1% of patients with Cushing's syndrome (CS)
      have a BCT. Typical BCTs rarely metastasize. We here present a patient with
      ectopic CS caused by a typical BCT, which metastasized into a lymph node. This
      case suggests that the diagnostic work up of CS should be wide and include
      ectopic ACTH-secreting BCT, and that ACTH secretion can be correlated to a more
      aggressive type of typical BCTs.

PMID- 28449501
TI  - Transarterial embolization of intralobar pulmonary sequestration in a young adult
      with hemoptysis.
AB  - Intralobar pulmonary sequestration is a rare congenital malformation
      characterized by the presence of dysplastic lung that does not communicate with
      the tracheobronchial tree, and has aberrant systemic arterial supply. While most
      are asymptomatic, they rarely can present with hemoptysis, which has been
      traditionally managed with surgical resection of the sequestration. We report a
      case of an 18-year-old male who presented with acute large-volume hemoptysis on a
      background of recurrent minor episodes of hemoptysis, due to intralobar
      sequestration. He was successfully treated with transarterial embolization with a
      combination of polyvinyl alcohol (PVA) particles, gelfoam and coils.
      Transarterial embolization can be effective in managing emergent hemoptysis from
      pulmonary sequestration.

PMID- 28449503
TI  - Re-crossing the distal cell in bifurcation verified by using an enhanced stent
      visualization system and optical coherence tomography: a report of two cases.
AB  - The coronary guidewire re-crossing position before the final kissing balloon post
      dilation is important to reduce the incidence of incomplete stent apposition in
      bifurcation lesions. Angiography and intravascular ultrasonography are unreliable
      at detecting the site of wire re-crossing. The high resolution of optical
      coherence tomography (OCT) offers the advantage of precise assessment of
      construction in bifurcation. However, the OCT technique still has some
      limitations, including the requirement for additional contrast and expense. We
      present two cases where the ClearStent Live system technique was used to estimate
      the wire location, which was verified by using OCT. In conclusion, ClearStent can
      be used with or to replace the intracoronary imaging technique in selected cases.

PMID- 28449504
TI  - Malignant pheochromocytoma in the anterior mediastinum with sternal invasion: a
      case report.
AB  - Pheochromocytomas are catecholamine-producing neuroendocrine tumors that usually
      occur in the adrenal medulla or sympathetic paraganglia. Anterior mediastinum
      involvement with pheochromocytoma is rare and may not present with typical
      symptoms. Its clinical manifestation may be unclear and a high index of suspicion
      is required for accurate diagnosis. We report a rare case of pheochromocytoma of
      the anterior mediastinum in a 51-year-old female. A painful hard mass on the
      sternum was the only clinical manifestation. Imageological examination indicated
      that there might be a malignant mass on the anterior mediastinum and thoracic
      wall. The patient accepted surgical curettage and thoracic wall reconstruction.
      Based on pathological results and WHO definition, the final diagnosis was
      malignant pheochromocytoma. After six months follow-up, the patient had no
      recurrence or any symptom. Malignant pheochromocytoma in the anterior mediastinum
      invading the sternum is rare. A local painful mass may be the only clinical
      manifestation without special laboratory results. Surgery remains as the first
      choice for these patients. For this rare case, 3D reconstruction by special
      software may be a good method to realize individualized treatment. The final
      decision of the diagnosis should be based on pathological results, past medical
      history and WHO definition. Long-term follow-up is necessary, while other
      suspicious lesions should also be given sufficient attention.

PMID- 28449505
TI  - Pulmonary vein stump thrombosis after left pneumonectomy, diagnosed based on a
      high plasma D-dimer level: a case report.
AB  - A 69-year-old man with locally advanced squamous cell lung cancer in the left
      hilum underwent left upper sleeve lobectomy following neoadjuvant
      chemoradiotherapy with an S-1/cisplatin regimen. On postoperative day (POD) 5,
      the chest X-ray findings deteriorated, and computed tomography (CT) images showed
      pulmonary congestion of the left residual lung. We then performed emergent left
      completion pneumonectomy. Although the Postoperative course after re-operation
      was uneventful, and the patient was scheduled to be discharged on POD 12 when the
      serum creatinine level and plasma D-dimer level increased to 1.34 mg/dL and 17.4
      ug/mL respectively. CT images revealed a giant thrombus in the left superior
      pulmonary vein (LSPV) stump, and we immediately started anticoagulant therapy of
      apixaban at 10 mg/day. We confirmed that the thrombus was reduced in size on POD
      30, and the patient was discharged without any further complications. The
      elevated plasma D-dimer level was a key finding in this case for diagnosing
      pulmonary vein stump thrombosis (PVT) after left lung surgery. The 23 reported
      cases of PVT were found incidentally through follow-up CT scan or after serious
      complications occurred. This is the first case reporting the utility of the
      plasma D-dimer test for diagnosing PVT after surgical resection of the left lung.
      Early detection of PVT by a plasma D-dimer test may therefore positively
      contribute to better outcomes in the postoperative course of surgical resection
      of the left lung.

PMID- 28449506
TI  - Surgical resection of right ventricular rhabdomyoma under the guidance of
      transesophageal echocardiography on a beating heart.
AB  - Cardiac rhabdomyoma, a type of benign myocardial tumor, is regarded as the most
      common fetal cardiac tumor. Rhabdomyomas are usually found before birth or during
      the first year of life. It is widely accepted that rhabdomyomas are strongly
      associated with tuberous sclerosis, and tend to regress spontaneously without
      surgical excision. However, if the tumor has caused significant obstruction or
      refractory arrhythmias, the surgery should be advocated. Most of the surgeries
      for pediatric cardiac tumors are performed under cardiopulmonary bypass (CPB)
      with cardioplegia. Here, we present a case of successful resection of a right
      ventricular rhabdomyoma obstructing the right ventricular outflow tract (RVOT)
      and involving pulmonary valve annulus in an infant, performed under the guidance
      of transesophageal echocardiography (TEE) on a beating heart.

PMID- 28449507
TI  - Primary mediastinal myelolipoma: a case report and literature review.
AB  - Myelolipoma is a kind of rare benign tumour composed of mature adipocytes and
      hemopoietic elements, and is most often found in the adrenal glands. Primary
      mediastinal myelolipoma (PMM) more rarely happens and has no definite symptoms,
      and mediastinal masses are usually found in chest examination. The patients
      normally receive a surgical resection and have a favorable prognosis after
      postoperative pathological diagnosis. Here, we present the case of PMM, which was
      resected via video-assisted thoracic surgery (VATS), and investigate recent
      correlative literatures to summarize its etiology, histopathology, differential
      diagnosis and therapeutic method. In this way, we aim to improve clinical
      doctors' understanding of this disease.

PMID- 28449508
TI  - Avoiding completion pneumonectomy by omentopexy for bronchial dehiscence.
AB  - A 56-year-old man underwent right upper sleeve lobectomy with mediastinal lymph
      node dissection after induction chemoradiotherapy (CRT) for advanced non-small
      cell lung cancer (NSCLC). The patient developed anastomotic dehiscence 11 days
      postoperatively. A fistula measuring 10 mm in diameter was found around the
      transition region between cartilage and membranous portions of the bronchus. To
      avoid completion right pneumonectomy, omentopexy was performed to cover the
      bronchial dehiscence and facilitate healing. The patient's condition improved
      after a redo operation with surveillance bronchoscopy to check the anastomotic
      status. Omentopexy may be a feasible treatment option for bronchial dehiscence
      and could help to avoid completion pneumonectomy (CP).

PMID- 28449509
TI  - Rapid response in a critical lung adenocarcinoma presenting as large airway
      stenoses after receiving stent implantation and sequential rebiopsy guided ALK
      inhibitor therapy: a case report.
AB  - Airway stent implantation can improve the symptoms of airway stenosis caused by a
      malignant tumor immediately. However, stent implantation is only a palliative
      therapy and disease will quickly progress without subsequent treatment. Targeted
      therapy can provide accurate etiological treatment for patients with critical
      lung cancer who cannot receive chemotherapies. In our clinic, we encountered a 50
      year-old male presenting with stage IV lung adenocarcinoma. He failed both the
      first-line and second-line chemotherapies and suffered severe complex left and
      right main bronchial stenoses caused by tumor invasion. An emergency stent was
      implanted to relieve dyspnea symptoms. At nearly the same time, he was detected
      to have an ALK gene fusion mutation upon rebiopsy and subsequently began
      crizotinib therapy. A short time later his obstructed airway returned to normal
      and lesions in the lung were miraculously reduced. This case indicates that the
      combination of stent implantation and real-time rebiopsy guided targeted therapy
      brings a new hope for patients with critical lung cancer.

PMID- 28449510
TI  - Chondromatous hamartoma of cervical esophagus: a case report and literature
      review.
AB  - Esophageal chondromatous hamartomas are very rare tumors, characterized by
      proliferating hyaline cartilage cells. We described the case of a 64-year-old
      woman, with a progressive foreign body sensation in the laryngopharynx caused by
      an intraluminal pedicled mass. Transcervical esophagectomy was performed and
      intraoperative biopsy revealed the mass was a cervical esophageal chondromatous
      hamartoma. The patient's postoperative course was uneventful and she recovered
      well. A review of the literature was conducted, and the symptoms, locations,
      histopathology findings, treatment methods and follow up results of esophageal
      hamartoma cases were summarized. We found that pre-operative endoscopic
      ultrasonography-guided fine-needle aspiration (EUS-FNA) can aid in diagnosis and
      that aggressive surgical treatment should be recommended for cervical esophageal
      hamartomas.

PMID- 28449511
TI  - Delayed-onset tension hemothorax following blunt trauma and the rupture of a
      previously undiagnosed aberrant right subclavian artery.
AB  - An arteria lusoria is a well-known anatomic variant of the right subclavian
      artery. We describe a patient in whom an arteria lusoria injury was revealed by
      delayed-onset tension hemothorax following blunt trauma to the thorax.

PMID- 28449512
TI  - Primary tracheal schwannoma treated by surgical resection: a case report.
AB  - The rarity and non-specific symptoms of benign primary tracheal tumors always
      leaded to misdiagnosis and delayed treatment, and also undefined the optimal
      treatment. In this case, a 45-year-old woman had a history of progressive
      shortness of breath and dry cough for several years, CT scan revealed an intra
      luminal tracheal mass invaded the left side of tracheal wall. After being located
      by bronchoscope preoperatively, the tumor was removed by surgical resection. The
      tumor was 1.5 cm in diameter with intact capsule. The pathological result
      confirmed the diagnosis of schwannoma.

PMID- 28449513
TI  - Thoracoscopic management of incarcerated lung herniation after blunt chest
      trauma: a case report and literature review.
AB  - Traumatic lung herniation is a rare condition that is usually treated with
      thoracotomy and pericostal fixation of adjacent ribs with sutures. We described a
      traumatic lung herniation case successfully managed with hernia reduction and
      double-layered repair of the intrathoracic defect, completed via a total
      thoracoscopic approach.

PMID- 28449514
TI  - Left ventricular outflow tract obstruction due to a left ventricular myxoma that
      was misidentified as an accessory mitral valve tissue.
AB  - We report obstruction of the left ventricle outflow tract (LVOT) caused by
      cardiac myxoma that was misidentified as an accessory mitral valve tissue
      preoperatively. A 65-year-old woman presented with chest discomfort that
      persisted for 7 days. Transthoracic echocardiography (TTE) revealed a mobile, low
      echogenic, balloon-shaped mass attached to the anterior mitral valve leaflet and
      papillary muscle, which was suspected to be an accessory mitral valve tissue.
      Because the mass caused LVOT obstruction and it could result in hemodynamic
      instability, emergency operation was performed. Intraoperative transesophageal
      echocardiography (TEE) was performed, and the mass had irregular margins and was
      pedunculated, with a stalk originating from the left ventricle (LV) wall and
      extending to the lateral chordae of the mitral valve. The surgeon excised the
      mass filled with the myxomatous mass, which was yellowish and gelatinous and had
      a stiff stalk, and histopathologic diagnosis confirmed a myxoma. Although mitral
      valve or LV myxomas are rare, TEE is a useful tool for distinguishing a myxoma
      from other intracardiac masses, such as vegetation or an accessory mitral valve
      tissue.

PMID- 28449515
TI  - Incomplete coronary revascularization: a cautionary tale.

PMID- 28449516
TI  - Long term oxygen therapy-it is still relevant?

PMID- 28449517
TI  - The EMPIRICUS trial-the final nail in the coffin of empirical antifungal therapy
      in the intensive care unit?

PMID- 28449518
TI  - A greater quality of clinical evidence is needed.

PMID- 28449519
TI  - Postoperative radiotherapy and lung cancer in stage III: helpful or harmful.

PMID- 28449520
TI  - Surgeon proficiency and outcomes in esophagectomy: a perspective and comment on
      an analysis of the Swedish Cancer Registry.

PMID- 28449521
TI  - Cancer of the esophagus and esophagogastric junction: an 8th edition staging
      primer.

PMID- 28449522
TI  - Pathological upstaging and treatment strategy of clinical stage I small cell lung
      cancer following surgery.

PMID- 28449523
TI  - What could be the key elements to determine the optimal number of lymph nodes
      sampled?

PMID- 28449524
TI  - A mighty oak in the rapidly expanding field of checkpoint inhibition for NSCLC.

PMID- 28449525
TI  - Recalcitrant small cell lung cancer: the argument for optimism.

PMID- 28449526
TI  - Recurrent aortic dissection: a challenging but rare dilemma.

PMID- 28449527
TI  - Invited Editorial on "the timing of surgery after neoadjuvant chemoradiation in
      locally advanced non-small cell lung cancer".

PMID- 28449528
TI  - The link between tuberculosis and body mass index.
AB  - The evidence behind the strong correlation between reactivation of tuberculosis
      (TB) and low body mass index (BMI) was reviewed. This strong association between
      TB and BMI occurred only with pulmonary TB and not extra-pulmonary TB, indicating
      that a low-BMI body build may in some way predispose to TB reactivation in the
      lungs. A possible explanation may be the congenital apical lung bullae that occur
      in 15% of the population and are likely to enlarge in young low-BMI males since
      biomechanical modeling of pleural stress has shown a massive 40x increase in
      apical pleural stress in low antero-posterior (AP) diameter chests associated
      with a low-BMI build. This suggests that pre-existing lung cavities may
      predispose to TB reactivation instead of current thinking that cavitation occurs
      after reactivation. Supporting this hypothesis is the relatively common incidence
      of both TB and primary spontaneous pneumothorax (PSP) occurring simultaneously.
      Furthermore, this hypothesis also gives a potential explanation for the apical
      location of secondary TB in the lower lobe as the conventional explanations of
      high apical oxygen levels and gravity appear to be invalid for the lower lobe.
      This opens up the possibility of a clinical trial that low-dose computerized
      tomography (CT) may be used to screen for the presence of subclinical apical
      bullae in low-BMI, high TB risk cohorts.

PMID- 28449529
TI  - Do hospitals need oncological critical care units?
AB  - Since the inception of critical care as a formal discipline in the late 1950s, we
      have seen rapid specialization to many types of intensive care units (ICUs) to
      accommodate evolving life support technologies and novel therapies in various
      disciplines of medicine. Indeed, the field has expanded such that specialized
      ICUs currently exist to address critical care problems in medicine, cardiology,
      neurology and neurosurgery, trauma, burns, organ transplant and cardiothoracic
      surgeries. Specialization does not only need new infrastructure, but also
      training and staffing of health care providers, ancillary staff, and development
      and implementation of processes of care. Oncology is another branch of medicine
      with growing ICU needs. Given the rise in cancer incidence worldwide and better
      survival rates alongside advances in chemotherapeutic and surgical options, more
      cancer patients are nowadays requiring advanced life support for cancer-related
      complications, treatment-related toxicities and severe infections. Here we
      provide a brief summary of the current evidence supporting the specialization of
      critical care and explore three different models of care for critically ill
      cancer patients, including the development of a specialized oncological ICU.
      Finally, we also discuss recently published and future research related to the
      care of critically ill cancer patients.

PMID- 28449530
TI  - Quality improvement in the ICU: treat first what kills first.
AB  - Professionals in the ICU, like nurses and doctors, are constantly working on
      quality improvement by developing protocols and monitoring the implementation
      with indicators. Protocols and quality indicators are usually based on evidence.
      Studies on quality improvement often measure the effect of protocols after
      implementation but frequently cannot replicate the results of the previously
      performed RCTs in clinical practice. Amongst other reasons, this is due to the
      selection of patients that are included in RCTs. Several quality improvement
      initiatives can be studied together in daily practice as a bundle with a
      multifaceted approach. A recent study is discussed that shows that this approach
      can only give significant results when the interventions are focussed on the main
      processes that are related to the chosen outcome measures. Several different
      reasons are apparently the cause that quality improvement studies often reveal
      negative results. Quality improvement studies need to have a rigorous design and
      well-chosen endpoints.

PMID- 28449531
TI  - Ablation of atrial fibrillation: single-shot techniques poised to dominate rhythm
      control strategies/the future is here.
AB  - Over the recent years, the advent of single-shot techniques, such as circular
      catheter and cryoballoon ablation, has ushered in a new era in the catheter
      ablation approach and rhythm control strategies of patients with atrial
      fibrillation (AF). These techniques make it easier to navigate the heart and have
      the potential to decrease the threshold for, expand the access to, and increase
      patient and physician acceptance of rhythm-control therapies, that may lead to
      reduction of the AF disease burden and its socioeconomic impact. Due to technical
      issues the circular catheter technique is lagging behind, however the cryoballoon
      approach is progressing at a faster pace both in the field of technical
      advancements and clinical studies, all contributing to its rapid penetration in
      the electrophysiological community and rhythm management approaches toward the
      commonest cardiac arrhythmia. Comparative studies of the conventional point-by
      point radiofrequency (RF) ablation technique and the cryoablation approach to
      pulmonary vein isolation (PVI), which constitutes the cornerstone of all ablation
      methods, seem to favor the cryoablation technique in certain aspects. The results
      of current studies converge in their conclusion that cryoablation employing
      current generation cryoballoons is a simplified and faster method compared to the
      conventional technique in achieving effective and durable PVI. Furthermore,
      investigators have recently proposed particular tips and parameters to serve as
      reliable predictors of successful and durable PVI that may enhance the clinical
      success of this single-shot ablation technique. These issues will be discussed in
      this overview and placed into perspective.

PMID- 28449532
TI  - The future of hybrid ablation: an emerging need for an anticoagulation protocol
      for thoracoscopic ablation.
AB  - The midterm efficacy of hybrid ablation of atrial fibrillation (AF) reported in
      recent papers is about 70% in terms of sinus rhythm maintenance without
      antiarrhythmic drugs. Bearing in mind that the majority of patients enrolled are
      patients with persistent and long-standing persistent AF, the reported efficacies
      seem to be very good. Despite the high efficacies, safety remains a critical
      issue in hybrid, and especially thoracoscopic ablations. The frequency of
      complications during thoracoscopic ablations is more than 10% in the majority of
      reports. Most are short-term with no sequelae (such as pneumothorax or
      pneumonia); however, life-threatening complications have also been described,
      e.g., a sternotomy in response to a laceration of the left atrium (LA). One of
      the most serious ablation complications is stroke. The rate of strokes, which has
      been reported during or shortly after thoracoscopic ablation, seems to be higher
      than the rate reported after catheter ablation. This is especially true in papers
      describing thoracoscopic ablations that were not immediately followed by a
      catheter ablation. A possible explanation is differences in anticoagulation
      management during the two procedures. During catheter endocardial procedures, a
      standard anticoagulation protocol exists and is routinely applied; however, there
      is no such set of recommendations for anticoagulation during the thoracoscopic
      phase of an ablation. It seems probable that, in many cases, no anticoagulation
      is used during thoracoscopic ablations. Moreover, whatever anticoagulation
      protocol is used during thoracoscopic ablations often goes unreported. A
      discussion about the best anticoagulation strategy during thoracoscopic ablation
      is urgently needed. In the future, standards of anticoagulation during
      thoracoscopic ablation should be clearly reported, just as they are now for
      catheter ablations.

PMID- 28449533
TI  - Can mathematics replace anatomy to establish recommendations in lung cancer
      surgery?
AB  - The greater the number of lymph node (LN) sampled (NLNsS) during lung cancer
      surgery, the lower the risk of underestimating the pN-status and the better the
      outcome of the pN0-patients due to stage-migration. Thus, regarding LN sampling
      "to be or not to be", number is the question. Recent studies advocate removing 10
      LNs. The most suitable NLNsS is unfortunately impossible to establish by
      mathematics. A too high NLNsS variability exists, based on anatomy, surgery and
      pathology. The methodology may vary according to Inter-institutional differences
      in the surgical approach regarding LN inspection and number sampling. The NLNsS
      increases with the type of resection: sublobar, lobectomy or pneumonectomy.
      Concerning pathology, one LN may be divided into several pieces, leading to
      number overestimation. The pathological examination is limited by the number of
      slices analyzed by LN. The examined LNs can arbitrarily depend on the probability
      of detecting nodal metastasis. In fact, the only way to ensure the best NLNsS and
      the best pN-staging is to remove all LNs from the ipsilateral mediastinal and
      hilar LN-stations as they are discovered by thoroughly dissecting their
      anatomical locations. In doing so, a deliberate lack of harvest of LNs is
      unlikely, number turns out not to be the question anymore and a low NLNsS no
      longer means incomplete surgery. This prevents from judging as incomplete a
      complete LN dissection in a patient with a small NLNsS and from considering as
      complete a true incomplete one in a patient with a great NLNsS. Precise
      information describing the course of the operation and furnished in the surgeon's
      reports is also advisable to further improve the quality of LN-dissection, which
      ultimately might be beneficial in the long-term to patients. However, that
      procedure is of limited interest in pN-staging if LNs are not thoroughly examined
      and also described by the pathologist.

PMID- 28449534
TI  - Safety profile of EGFR-targeted hybrid vector system composed of PAMAM dendrimer
      and oncolytic adenovirus.

PMID- 28449536
TI  - Cell nucleus and English letters.

PMID- 28449535
TI  - The use of electron microscopy for diagnosis of malignant pleural mesothelioma.

PMID- 28449537
TI  - Erratum to "The total artificial heart".
AB  - [This corrects the article on p. 2172 in vol. 7, PMID: 26793338.].

PMID- 28449538
TI  - Shape and Size-Dependent Magnetic Properties of Fe3O4 Nanoparticles Synthesized
      Using Piperidine.
AB  - In this article, we proposed a facile one-step synthesis of Fe3O4 nanoparticles
      of different shapes and sizes by co-precipitation of FeCl2 with piperidine. A
      careful investigation of TEM micrographs shows that the shape and size of
      nanoparticles can be tuned by varying the molarity of piperidine. XRD patterns
      match the standard phase of the spinal structure of Fe3O4 which confirms the
      formation of Fe3O4 nanoparticles. Transmission electron microscopy reveals that
      molar concentration of FeCl2 solution plays a significant role in determining the
      shape and size of Fe3O4 nanoparticles. Changes in the shape and sizes of Fe3O4
      nanoparticles which are influenced by the molar concentration of FeCl2 can easily
      be explained with the help of surface free energy minimization principle.
      Further, to study the magnetic behavior of synthesized Fe3O4 nanoparticles,
      magnetization vs. magnetic field (M-H) and magnetization vs. temperature (M-T)
      measurements were carried out by using Physical Property Measurement System
      (PPMS). These results show systematic changes in various magnetic parameters like
      remanent magnetization (Mr), saturation magnetization (Ms), coercivity (Hc), and
      blocking temperature (T B) with shapes and sizes of Fe3O4. These variations of
      magnetic properties of different shaped Fe3O4 nanoparticles can be explained with
      surface effect and finite size effect.

PMID- 28449539
TI  - Effect of Mechanical Stresses in Rapidly Heated Fe73Cu1Nb3Si16B7 Ribbon Arising
      During the Ring Core Formation on Their Magnetic Properties.
AB  - The influence of winding-induced mechanical stresses on the magnetic anisotropy
      and core loss in toroidal cores made of Fe73Cu1Nb3Si16B7 ribbon is studied. The
      ribbon for the cores was rapidly pre-heated under tensile stress up to 120 MPa.
      It was found that magnetic characteristics of the material (magnetic anisotropy
      energy and the core loss) can be controlled by varying the tensile stress during
      the preliminary rapid heating of the ribbon. It was shown that with reducing core
      diameter, the magnetic anisotropy energy and core loss significantly increase.
      However, relatively high winding-induced core loss in small cores can be
      significantly reduced by increasing tensile stresses applied to the ribbon during
      pre-heating.

PMID- 28449540
TI  - Anisotropy of Single-Crystal Silicon in Nanometric Cutting.
AB  - The anisotropy exhibited by single-crystal silicon in nanometric cutting is very
      significant. In order to profoundly understand the effect of crystal anisotropy
      on cutting behaviors, a large-scale molecular dynamics model was conducted to
      simulate the nanometric cutting of single-crystal silicon in the (100)[0-10],
      (100)[0-1-1], (110)[-110], (110)[00-1], (111)[-101], and (111)[-12-1] crystal
      directions in this study. The simulation results show the variations of different
      degrees in chip, subsurface damage, cutting force, and friction coefficient with
      changes in crystal plane and crystal direction. Shear deformation is the
      formation mechanism of subsurface damage, and the direction and complexity it
      forms are the primary causes that result in the anisotropy of subsurface damage.
      Structurally, chips could be classified into completely amorphous ones and
      incompletely amorphous ones containing a few crystallites. The formation
      mechanism of the former is high-pressure phase transformation, while the latter
      is obtained under the combined action of high-pressure phase transformation and
      cleavage. Based on an analysis of the material removal mode, it can be found that
      compared with the other crystal direction on the same crystal plane, the (100)[0
      10], (110)[-110], and (111)[-101] directions are more suitable for ductile
      cutting.

PMID- 28449541
TI  - Nanoscale Observation of Dehydration Process in PHEMA Hydrogel Structure.
AB  - One of the most important field of interest in respect to hydrogel materials is
      their capability to water storage. The problem mentioned above plays an important
      role regarding to diffusion of fluid media containing nanoparticles, what is very
      useful in biomedical applications, such as artificial polymeric implants, drug
      delivery systems or tissue engineering.In presented work, dehydration process in
      hydrogels used in ophthalmology as intraocular lenses was observed. Before
      measurements studied materials were immersed in deionized water and saline
      solution to obtain equilibrium swelling state. Studies of the dehydration process
      were carried out by use of gravimetric analysis, Fourier-Transform Infrared and
      Positron Annihilation Lifetime Spectroscopy. Obtained results revealed changes in
      hydrogen bonding structure and free volume holes induced by saline solution
      ingredients.

PMID- 28449542
TI  - Estimation of the Number of Quantum Dots Immobilized on an Ultra-flat Au Surface.
AB  - Quantum dots (QDs) were immobilized on an ultra-flat Au surface by using amide
      binding between the carboxyl groups on the QDs and the amino groups of the self
      assembled monolayer on the surface. The number density of the QDs estimated by
      atomic force microscopy (AFM) agreed with the quantity of QDs estimated by X-ray
      photoelectron spectroscopy and fluorescence microscopy. QDs were also immobilized
      on dot patterns fabricated by e-beam lithography. AFM was able to identify
      clusters of just a few QDs on the dot patterns, whose minimum designed size was
      50 nm * 50 nm per dot.

PMID- 28449543
TI  - Nanoporous Cyanate Ester Resins: Structure-Gas Transport Property Relationships.
AB  - This contribution addresses the relationships between the structure and gas
      transport properties of nanoporous thermostable cyanate ester resins (CERs)
      derived from polycyclotrimerization of 1,1'-bis(4-cyanatophenyl)ethane in the
      presence of 30 or 50 wt% of inert high-boiling temperature porogens (i.e.,
      dimethyl- or dibutyl phthalates), followed by their quantitative removal. The
      nanopores in the films obtained were generated via a chemically induced phase
      separation route with further porogen extraction from the densely crosslinked
      CERs. To ensure a total desorption of the porogen moieties from the networks, an
      additional short-term thermal annealing at 250  degrees C was performed. The
      structure and morphology of such nanoporous CER-based films were investigated by
      FTIR and SEM techniques, respectively. Further, the gas transport properties of
      CER films were analyzed after the different processing steps, and relationships
      between the material structure and the main gas transport parameters were
      established.

PMID- 28449544
TI  - Measurements of Defect Structures by Positron Annihilation Lifetime Spectroscopy
      of the Tellurite Glass 70TeO2-5XO-10P2O5-10ZnO-5PbF2 (X = Mg, Bi2, Ti) Doped with
      Ions of the Rare Earth Element Er3.
AB  - The objective of the study was the structural analysis of the 70TeO2-5XO-10P2O5
      10ZnO-5PbF2 (X = Mg, Bi2, Ti) tellurite glasses doped with ions of the rare-earth
      elements Er3+, based on the PALS (positron annihilation lifetime spectroscopy)
      method of measuring positron lifetimes. Values of positron lifetimes and the
      corresponding intensities may be connected with the sizes and number of
      structural defects, the sizes of which range from a few angstroms to a few dozen
      nanometers. Experimental positron lifetime spectrum revealed existence of two
      positron lifetime components tau 1 andtau 2. Their interpretation was based on
      two-state positron trapping model where the physical parameters are the positron
      annihilation rate and positron trapping rate.

PMID- 28449545
TI  - Structural Variety and Adsorptive Properties of Mesoporous Silicas with
      Immobilized Oligosaccharide Groups.
AB  - In this research, we report on the synthesis of mesoporous silicas with various
      quantities of immobilized oligosaccharide groups and different pore ordering
      degree. The hydrothermal co-condensation of tetraethyl orthosilicate and beta
      cyclodextrin-containing organosilane in the presence of cetyltrimethylammonium
      bromide template was employed. The purpose of this investigation was to show the
      opportunity of increasing beta-cyclodextrin content in silica matrix by changing
      the molar ratio of initial reagents during organosilane synthesis and to
      determine whether the enhancing of immobilized groups on the surface influences
      on model aromatic compound adsorption from water. It was prepared several beta
      cyclodextrin-organosilanes by modification of (3-aminopropyl)triethoxysilane with
      oligosaccharide (the molar composition of reaction mixtures were 1:1, 3:1, and
      5:1) with using N,N'-carbonyldiimidazole as linking agent. Three types of MCM-41
      materials were obtained with 0.018, 0.072, and 0.095 mmol g-1 beta-cyclodextrin
      group loading according to chemical analysis of silicas. The IR spectroscopy and
      potentiometric titration were also performed to confirm the presence of
      functional groups in the silica matrix. Nitrogen sorptometry experiments
      exhibited the decrease of high surface area (from 812 to 457 m2 g-1) and the
      average pore diameter (from 1.06 to 0.60 cm3 g-1) of synthesized silicas with
      increasing of immobilized oligosaccharide groups. The influence of beta
      cyclodextrin-organosilane presence on the forming of hexagonally arranged porous
      structure of silicas was evaluated by X-ray diffraction and TEM analyses. As the
      loading of oligosaccharide groups increases in obtained silicas, the (100) reflex
      in diffraction patterns is even less intense and broader, denoting the decrease
      of long-range pore ordering. Adsorption experiments were carried out to study the
      effect of beta-cyclodextrin groups' attendance in silica matrix on benzene
      uptakes from aqueous solutions. Experimental kinetic curves of benzene adsorption
      on synthesized silicas were compared with theoretical models of Lagergren and Ho
      McKay for pseudo-first and pseudo-second-order processes. Langmuir and Freundlich
      isotherm models were used to evaluate adsorption processes and parameters.
      Obtained beta-cyclodextrin-containing MCM-41 silicas demonstrate adsorption level
      performance of known samples and could be very promising for benzene uptakes from
      aqueous solutions in water treatment processes.

PMID- 28449546
TI  - pMOSFETs Featuring ALD W Filling Metal Using SiH4 and B2H6 Precursors in 22 nm
      Node CMOS Technology.
AB  - In this paper, pMOSFETs featuring atomic layer deposition (ALD) tungsten (W)
      using SiH4 and B2H6 precursors in 22 nm node CMOS technology were investigated.
      It is found that, in terms of threshold voltage, driving capability, carrier
      mobility, and the control of short-channel effects, the performance of devices
      featuring ALD W using SiH4 is superior to that of devices featuring ALD W using
      B2H6. This disparity in device performance results from different metal gate
      induced strain from ALD W using SiH4 and B2H6 precursors, i.e. tensile stresses
      for SiH4 (~2.4 GPa) and for B2H6 (~0.9 GPa).

PMID- 28449547
TI  - Cobalt Oxide Porous Nanofibers Directly Grown on Conductive Substrate as a
      Binder/Additive-Free Lithium-Ion Battery Anode with High Capacity.
AB  - In order to reduce the amount of inactive materials, such as binders and carbon
      additives in battery electrode, porous cobalt monoxide nanofibers were directly
      grown on conductive substrate as a binder/additive-free lithium-ion battery
      anode. This electrode exhibited very high specific discharging/charging
      capacities at various rates and good cycling stability. It was promising as high
      capacity anode materials for lithium-ion battery.

PMID- 28449548
TI  - Vibration-Induced Property Change in the Melting and Solidifying Process of
      Metallic Nanoparticles.
AB  - Tuning material properties in the 3-D printing process of metallic parts is a
      challenging task of current interests. Much research has been conducted to
      understand the effects of controlling parameters such as the particle geometry
      (size and shape), heating, and cooling ways on the outcome of the printing
      process. However, nothing has been done to explore the system vibration effect.
      This letter reports our findings on the vibration-induced property change in the
      melting and solidifying process of silver nanoparticles with the use of molecular
      dynamics simulation. We find that the increase of system vibration magnitude
      would increase the number fraction of disordered atoms, which in turn changes the
      nanostructure of solidified products. For a given system vibration magnitude, the
      number fraction of disordered atoms reaches the maximum around the system natural
      frequency so that the stiffness of solidified products becomes the minimum. Since
      this trend is not affected by the system size, the above findings reveal a
      feasible path toward the real-time tuning of material properties for advancing
      additive manufacturing.

PMID- 28449549
TI  - Fabrication of TiO2 Nanosheet Aarrays/Graphene/Cu2O Composite Structure for
      Enhanced Photocatalytic Activities.
AB  - TiO2 NSAs/graphene/Cu2O was fabricated on the carbon fiber to use as
      photocastalysts by coating Cu2O on the graphene (G) decorated TiO2 nanosheet
      arrays (NSAs). The research focus on constructing the composite structure and
      investigating the reason to enhance the photocatalytic ability. The
      morphological, structural, and photocatalytic properties of the as-synthesized
      products were characterized. The experimental results indicate that the better
      photocatalytic performance is ascribed to the following reasons. First, the TiO2
      NSAs/graphene/Cu2O composite structure fabricated on the carbon cloth can form a
      3D structure which can provide a higher specific surface area and enhance the
      light absorption. Second, the graphene as an electron sink can accept the
      photoelectrons from the photoexcited Cu2O which will reduce the recombination.
      Third, the TiO2 nanosheet can provide more favorable carrier transportation
      channel which can reduce the recombination of carriers. Finally, the Cu2O can
      extend the light absorption range.

PMID- 28449550
TI  - Modeling the Effects of Nanopatterned Surfaces on Wetting States of Droplets.
AB  - An analytic thermodynamic model has been established to quantitatively
      investigate the wetting states of droplets on nanopatterned surfaces. Based on
      the calculations for the free energies of droplets with the Wenzel state and the
      Cassie-Baxter state, it is found that the size and shape of nanostructured
      surfaces play crucial roles in wetting states. In detail, for nanohole-patterned
      surfaces, the deep and thin nanoholes lead to the Cassie-Baxter state, and
      contrarily, the shallow and thick nanoholes result in the Wenzel state. However,
      the droplets have the Wenzel state on the patterned surfaces with small height
      and radii nanopillars and have the Cassie-Baxter state when the height and radii
      of nanopillars are large. Furthermore, the intuitive phase diagrams of the
      wetting states of the droplet in the space of surface geometrical parameters are
      obtained. The theoretical results are in good agreement with the experimental
      observations and reveal physical mechanisms involved in the effects of
      nanopatterned surfaces on wetting states, which implies that these studies may
      provide useful guidance to the conscious design of patterned surfaces to control
      the wetting states of droplets.

PMID- 28449551
TI  - A Survey of Korean Physicians' Prescription Patterns for Allergic Rhinitis.
AB  - OBJECTIVES: The aim of this study was to compare the prescription patterns
      according to characteristics of physicians using a survey distributed amongst
      physicians in Korea. METHODS: We surveyed the prescription patterns for allergic
      rhinitis (AR) of the members of the Korean Academy of Asthma, Allergy and
      Clinical Immunology (KAAACI) and the Korean Association of Otorhinolaryngologists
      (KAO). Questionnaire contained 4 categories with 28 queries. 448 physicians
      including 98 internal medicine (IM), 113 pediatrics (PED), and 237
      otorhinolaryngology (ENT) were responded. RESULTS: Although the Allergic Rhinitis
      and its Impact on Asthma (ARIA) guidelines are most frequently used in all
      specialties, seasonal or perennial AR is the most frequent classification system.
      For the definitive diagnosis of AR, ENT physicians reported using multiple
      allergen simultaneous test (MAST)/radio allergy sorbent test (RAST) more than
      others (IM, 10.9%; PED, 20.6%; ENT, 44.2%; P<0.001). In treatment, most
      physicians reported that antihistamine medication is the initial treatment for
      AR. PED physicians prescribed fewer intranasal steroid to combinations with an
      antihistamine than other specialists (IM, 65.3%; PED, 42.5%; ENT, 63.3%), but
      preferred leukotriene antagonists (IM, 4.1%; PED, 23.0%; ENT, 3.9%; P=0.041).
      Overall, 53% (235/448) of the physicians performed allergen immunotherapy (AIT),
      and IM administers the most AIT (IM, 71.6%; PED, 42.0%; ENT, 39.5%; P=0.019).
      Furthermore, university and general hospital physicians prescribed more AIT than
      doctors at other hospital types (university hospital, 76.4%; general hospital,
      64.3%; local hospital, 21.4%; private clinic, 20.2%; P<0.001). CONCLUSION: The
      prescription patterns for AR were different according to the physicians'
      characteristics and general rate of prescribing AIT is just about 53% in Korea.
      Thus, the development of complementary Korean-specific guidelines is needed and
      proper clinical instruction of AIT would be necessary.

PMID- 28449552
TI  - Effect of Proparacaine in a Mouse Model of Allergic Rhinitis.
AB  - OBJECTIVES: Lidocaine, a local anaesthetic is a treatment option in uncontrolled
      asthma due to its immunomodulatory effects. In the present study, proparacaine
      (PPC), a derivative of lidocaine was examined for its therapeutic application in
      a mouse model of allergic rhinitis. METHODS: The mice were grouped into 4 groups:
      control group, allergic rhinitis (AR) group, ciclesonide (CIC) group, and PPC
      group. Nasal symptom scores, eosinophil counts, goblet cell counts, and mast
      cells counts in the nasal mucosa were measured. Serum ovalbumin (OVA)-specific
      immunoglobulin (Ig) E, OVA-specific IgG1, OVA-specific IgG2a, interleukin (IL)-4,
      IL-5, and cortisol levels were measured. RESULTS: Intranasal administration of
      PPC significantly decreased nasal symptoms, number of eosinophils, goblet cells,
      and mast cells in the lamina propria of the nasal mucosa. Serum OVA-specific IgE,
      OVA-specific IgG1, OVA-specific IgG2a was significantly higher in the AR compared
      with the control group. Serum level of IL-4 was significantly lower in the CIC
      group and PPC group in comparison with AR group. Serum IL-5 showed no significant
      difference among all groups. No significant difference in serum cortisol levels
      was observed among the 4 groups. CONCLUSION: PPC appears to have a therapeutic
      potential in treatment of allergic rhinitis in a mouse model by reducing
      eosinophil, goblet cell, and mast cell infiltration in the nasal mucosa.

PMID- 28449553
TI  - Changes in the Reflux Symptom Index After Multilevel Surgery for Obstructive
      Sleep Apnea.
AB  - OBJECTIVES: This study evaluated whether the symptoms of laryngopharyngeal reflux
      (LPR) change after multilevel surgery for obstructive sleep apnea (OSA). METHODS:
      Patients who underwent multilevel surgery for OSA between April 2009 and
      September 2014 were enrolled in this study. All patients underwent preoperative
      polysomnography prior to surgery and were asked to complete the reflux symptom
      index (RSI) questionnaire before and after surgery. RESULTS: Of 73 enrolled
      patients, 24 (33%) reported an RSI score >13 and were thus classified as having
      reflux. The mean RSI score before surgery was 11.48+/-7.95; this number decreased
      to 4.95+/-6.19 after surgery (P<0.001). The rate of positive RSI responses was
      33% before surgery and 9% after surgery. Each variable that comprised the RSI
      improved significantly after surgery, except for difficulty with swallowing.
      Regarding the degree of RSI improvement after surgery, there were no significant
      differences between subgroups according to sex, age, body mass index, OSA
      severity, or surgical outcome. CONCLUSION: LPR symptoms are prevalent in OSA
      patients. Treatment for OSA using multilevel surgery potentially reduces the
      symptoms of LPR.

PMID- 28449554
TI  - A Study of Single Nucleotide Polymorphisms of Tumour Necrosis Factor alpha-1031
      And Tumour Necrosis Factor beta+ 252 in Chronic Rhinosinusitis.
AB  - OBJECTIVES: This case-controlled study aimed to identify the association of tumor
      necrosis factor (TNF)alpha-1031 and TNFbeta+ 252 gene polymorphisms between
      chronic rhinosinusitis (CRS) and healthy controls. Another purpose of this study
      was to investigate the associations of these gene polymorphisms with factors
      related to CRS. METHODS: All deoxyribonucleic acid (DNA) samples were genotyped
      for TNFalpha-1031 and TNFbeta+252 genes by mean of polymerase chain reaction
      (PCR) and restriction fragment length polymorphisms (RFLP). The statistical
      analysis were carried out using chi-square test or Fisher exact test to determine
      the associations of these gene polymorphisms in CRS. Multiple logistic regression
      was performed to evaluate the associations of these gene polymorphisms in CRS and
      its related risk factors. RESULTS: The genotype and allele frequencies of
      TNFalpha-1031 and TNFbeta+252 gene did not show any significant associations
      between CRS and healthy controls. However, a significantly statistical difference
      of TNFalpha-1031 was observed in CRS participants with atopy (P-value, 0.045;
      odds ratio, 3.66) but not in CRS with asthma or aspirin intolerance. CONCLUSION:
      Although the presence of TNFalpha-1031 and TNFbeta+252 gene polymorphisms did not
      render any significant associations between CRS and healthy control, this study
      suggests that TNFalpha-1031 gene polymorphisms in CRS patients with atopy may be
      associated with increase susceptibility towards CRS.

PMID- 28449555
TI  - Capsanthin Inhibits both Adipogenesis in 3T3-L1 Preadipocytes and Weight Gain in
      High-Fat Diet-Induced Obese Mice.
AB  - Adipogenesis in murine preadipocyte 3T3L-1 has been used as a model system to
      study anti-obese bioactive molecules. During adipogenesis in 3T3-L1
      preadipocytes, we found that capsanthin inhibited adipogenesis (IC50; 2.5 MUM)
      and also showed lipolytic activity in differentiated adipocytes from the
      preadipocytes (ED50; 872 nM). We identified that the pharmacological activity of
      capsanthin on adipogenesis in 3T3-L1 was mainly due to its adrenoceptor-beta2
      agonistic activity. In high-fat diet animal model study, capsanthin significantly
      enhanced spontaneous locomotive activities together with progressive weight-loss.
      The capsanthin-induced activation of kinetic behavior in mice was associated with
      the excessive production of ATP initiated by both the enhanced lipolytic activity
      together with accelerated oxidation of fatty acids due to the adrenoceptor beta2
      agonistic activity of capsanthin. Capsanthin also dose-dependently increased
      adiponectin and p-AMPK activity in high fat diet animals, suggesting that
      capsanthin has both anti-obesity and insulin sensitizing activities.

PMID- 28449556
TI  - Role of Sleep Disturbance in the Trajectory of Alzheimer's Disease.
AB  - Sleep disturbances such as insomnia, hypersomnia, and circadian rhythm
      disturbance are common in normal elderly and Alzheimer's disease (AD) patients.
      To date, special attention has been paid to sleep disturbance in the clinical
      course of AD insofar as the interaction of sleep disturbance with the
      pathogenesis of AD may impact the clinical course and cognitive function of AD
      patients. This review covers the bidirectional relationship between sleep
      disturbance and AD pathogenesis; the associations between sleep disturbance and
      AD-specific neurotransmitters, brain structure, and aspects of sleep disturbance
      in each phase of AD; and the effects of sleep disturbance on the cognitive
      functions of patients in each phase of AD. We consider several factors required
      to exactly interpret the results and suggest a direction for future studies on
      the role of sleep disturbance in AD.

PMID- 28449557
TI  - Wnt and GSK3 Signaling Pathways in Bipolar Disorder: Clinical and Therapeutic
      Implications.
AB  - The neurobiology of bipolar disorder, a chronic and systemic ailment is not
      completely understood. The bipolar phenotype manifests in myriad ways, and
      psychopharmacological agents like lithium have long term beneficial effects. The
      enzyme glycogen synthase kinase 3 (GSK3) has come into focus, as lithium and
      several other mood stabilizing medications inhibit its activity. This kinase and
      its key upstream modulator, Wnt are dysregulated in mood disorders and there is a
      growing impetus to delineate the chief substrates involved in the development of
      these illnesses. In May 2016, a comprehensive literature search was undertaken
      which revealed that there is over activity of GSK3 in bipolar disorder with
      deleterious downstream effects like proinflammatory status, increased oxidative
      stress, and circadian dysregulation leading to declining neurotrophic support and
      enhanced apoptosis of neural elements. By developing specific GSK3 inhibitors the
      progressive worsening in bipolar disorder can be forestalled with improved
      prospects for the sufferers.

PMID- 28449558
TI  - In SilicoModel-driven Assessment of the Effects of Brain-derived Neurotrophic
      Factor Deficiency on Glutamate and Gamma-Aminobutyric Acid: Implications for
      Understanding Schizophrenia Pathophysiology.
AB  - Objective: Deficient brain-derived neurotrophic factor (BDNF) is one of the
      important mechanisms underlying the neuroplasticity abnormalities in
      schizophrenia. Aberration in BDNF signaling pathways directly or circuitously
      influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA).
      For the first time, this study attempts to construct and simulate the BDNF
      neurotransmitter network in order to assess the effects of BDNF deficiency on
      glutamate and GABA. Methods: Using CellDesigner, we modeled BDNF interactions
      with calcium influx via N-methyl-D-aspartate receptor (NMDAR)- Calmodulin
      activation; synthesis of GABA via cell cycle regulators protein kinase B,
      glycogen synthase kinase and beta-catenin; transportation of glutamate and GABA.
      Steady state stability, perturbation time-course simulation and sensitivity
      analysis were performed in COPASI after assigning the kinetic functions,
      optimizing the unknown parameters using random search and genetic algorithm.
      Results: Study observations suggest that increased glutamate in hippocampus,
      similar to that seen in schizophrenia, could potentially be contributed by
      indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate
      decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to
      impaired transport via vesicular glutamate transporter, thereby further
      increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF
      also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity
      analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and
      CREB regulated transcription coactivator-1 played significant role in this
      network. Conclusion: The study presents in silicoquantitative model of
      biochemical network constituting the key signaling molecules implicated in
      schizophrenia pathogenesis. It provides mechanistic insights into putative
      contribution of deficient BNDF towards alterations in neurotransmitters and
      neuroplasticity that are consistent with current understanding of the disorder.

PMID- 28449559
TI  - Effects of Escitalopram on Anxiety in Patients with Acute Coronary Syndrome: A
      Randomized Controlled Trial.
AB  - Objective: There are no evidence-based practices for treating anxiety in patients
      with acute coronary syndrome (ACS). Thus, we investigated the effects of
      escitalopram on anxiety in this population. Methods: We enrolled 217 patients
      with ACS who met Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition (DSM-IV) criteria for depressive disorders into a randomized double-blind
      placebo-controlled study. Patients received either escitalopram or placebo over a
      24-week period. Anxiety symptoms were evaluated using the Hospital Anxiety and
      Depression Scale-anxiety subscale (HADS-A). A HADS-A score >7 was classified as
      an anxiety disorder. Baseline evaluations included sociodemographic and clinical
      characteristics, such as depressive symptoms, cardiovascular risk factors, and
      current cardiac status. Results: Independent of improvements in depression and
      without any differences in safety profiles, escitalopram treatment was
      significantly more efficacious in treating and reducing anxiety than placebo over
      a 24-week period. Conclusion: Escitalopram can be recommended as an effective and
      safe treatment option for anxiety in patients with ACS.

PMID- 28449560
TI  - Assessment of the Latent Adverse Events of Antipsychotic Treatment Using a
      Subjective Questionnaire in Japanese Patients with Schizophrenia.
AB  - Objective: The adverse effects of antipsychotic agents can have a marked
      influence on medication adherence. In this study, we. : investigated the adverse
      events of antipsychotics that are less likely to be reported by patients and the
      reasons why such symptoms remain latent. Methods: Data were collected by
      interviewing patients using a subjective questionnaire, and the associations
      between unreported symptoms and background factors were investigated. Results: A
      total of 306 patients with schizophrenia or schizoaffective disorder were
      examined. Their major symptoms were daytime sleepiness (50.0%), weight gain
      (42.2%), and sexual dysfunction (38.9%). Sexual dysfunction was nominal
      significantly more common among the patients that had been treated with
      antipsychotic agent polypharmacy (odds ratio [OR], 2.14; 95% confidence interval
      [CI], 1.07 to 4.30), and was nominal significantly more common among outpatients
      (OR, 1.78; 95% CI, 1.02 to 3.13). Only approximately 30% of the patients had
      reported their symptoms to their physicians. Conclusion: Patients receiving
      antipsychotic treatment tolerate some symptoms and do not feel able to report
      them to their physicians. The most common reason for this is an insufficient
      patient-physician relationship. Sexual dysfunction is especially hard to identify
      because it is a delicate problem, and our findings demonstrate that subjective
      questionnaires are helpful for detecting such symptoms.

PMID- 28449561
TI  - Differences in Resting-state Quantitative Electroencephalography Patterns in
      Attention Deficit/Hyperactivity Disorder with or without Comorbid Symptoms.
AB  - Objective: The aim of the present study was to evaluate the role of comorbid
      psychiatric symptoms on quantitative electroencephalogram (QEEG) activities in
      boys with the attention deficit/hyperactivity disorder (ADHD). Methods: All
      participants were male students in the second, third or fourth grade in
      elementary school. Therefore, there were no significant differences in age or
      sex. Participants with ADHD were assigned to one of three groups: pure ADHD
      (n=22), ADHD with depressive symptoms (n=11), or ADHD with problematic internet
      use (n=19). The Korean version of the Children's Depression Inventory and the
      Korean Internet Addiction Self-scale were used to assess depressive symptoms and
      problematic internet use, respectively. Resting-state EEG during eyes closed was
      recorded, and the absolute power of five frequency bands was analyzed: delta (1-4
      Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), and gamma (30-50 Hz).
      Results: The ADHD with problematic internet use group showed decreased absolute
      theta power at the central and posterior region compared with the pure ADHD
      group. However, The ADHD with depressive symptoms group showed no significant
      differences compared with the other groups. Conclusion: These findings will
      contribute to a better understanding of brain-based electrophysiological changes
      in children with ADHD in accordance with comorbid psychiatric symptoms.

PMID- 28449562
TI  - Longer Telomere Length of T lymphocytes in Patients with Early and Chronic
      Psychosis.
AB  - Objective: To investigate pathological conditions that act as sources of pro
      inflammatory cytokines and cytotoxic substances to examine telomere length (TL)
      in patients with either early (duration of illness [DI] <=5 years) or chronic (DI
      >5 years) psychosis using T lymphocytes. Methods: Based on these factors and the
      important role that T lymphocytes play in inflammation, the present study
      measured the TL of T lymphocytes in patients with either early or chronic
      psychosis. Additionally, smoking, metabolic syndrome, depression, and cognitive
      functioning were assessed to control for confounding effects. Results: TL was
      significantly longer in patients with early and chronic psychosis than in healthy
      control subjects and, moreover, the significance of these findings remained after
      controlling for age, smoking, metabolic syndrome, DI, chlorpromazine-equivalent
      dose, and cognitive functioning (F=9.57, degree of freedom=2, p<0.001).
      Additionally, the DI, chlorpromazine-equivalent doses, and the five-factor scores
      of the Positive and Negative Syndrome Scale were not significantly correlated
      with the TL of T lymphocytes in either all patients or each psychosis group.
      Conclusion: Possible mechanisms underlying the effects of antipsychotic
      medications on telomerase are discussed in the present study, but further studies
      measuring both telomerase activity and TL using a prospective design will be
      required.

PMID- 28449563
TI  - Relationship between Serum Bilirubin Levels and Metabolic Syndrome in Patients
      with Schizophrenia Spectrum Disorders.
AB  - Objective: We investigated the relationship between serum bilirubin levels and
      metabolic syndrome (MetS), and the longitudinal effects of baseline serum
      bilirubin concentrations on MetS in patients with schizophrenia spectrum
      disorders undergoing atypical antipsychotics. Methods: The sample of this study
      consisted of 131 patients with schizophrenia spectrum disorders. Waist
      circumference, blood pressure, and levels of triglycerides, high-density
      lipoprotein cholesterol, fasting glucose, and insulin were evaluated at baseline
      and at month six. Serum bilirubin levels were measured at baseline. Serum
      bilirubin levels of the patients with and without MetS criteria were compared. We
      also compared patients with high and low bilirubin levels (upper and lower 50th
      percentiles of serum bilirubin levels) in terms of MetS criteria, MetS frequency,
      and course of MetS. Results: Serum direct bilirubin levels were more consistently
      related to MetS and MetS-related variables. The waist circumference and
      triglyceride criteria for MetS were significantly related to low serum direct
      bilirubin at baseline; waist circumference and fasting glucose criteria, and
      insulin resistance were associated with low serum direct bilirubin at follow-up.
      MetS diagnosis and the presence of the waist circumference criterion were more
      frequent at the baseline and the follow-up in low bilirubin group. At the end of
      the follow-up period, the rate of reverse MetS was significantly higher in the
      high bilirubin group. Conclusion: Our results have suggested that serum direct
      bilirubin levels showed a more reliable and stable relationship with abdominal
      obesity for MetS components.in patients with schizophrenia spectrum disorders
      using antipsychotics. Further studies are required.

PMID- 28449564
TI  - Dehydroepiandrosterone Sulfate Level Varies Nonlinearly with Symptom Severity in
      Major Depressive Disorder.
AB  - Objective: The pathophysiology of major depressive disorder (MDD) is still not
      well understood. Conflicting results for surrogate. : biomarkers in MDD have been
      reported, which might be a consequence of the heterogeneity of MDD patients.
      Therefore, we aim to investigate how the severity of depression and various
      symptom domains are related to the levels of dehydroepiandrosterone sulfate (DHEA
      s) in MDD patients. Methods: We recruited 117 subjects from a general practice.
      Depressive symptoms were assessed using the Beck Depression Inventory (BDI).
      Depressive symptoms were divided into three subdomains according to BDI items;
      somatic symptoms, guilt and failure, and mood and inhibition. Results: In
      subjects with very-mild-to-moderate depression, the DHEA-s level increased as BDI
      score did. However, the DHEA-s levels in the subjects with severe depression were
      significantly lower than in subjects with moderate depression (p=0.003). DHEA-s
      level was correlated with the BDI subscore for guilt and failure in very-mild-to
      moderate depression (r=0.365, p=0.006). Conclusion: The DHEA-s level appears to
      be indicative of MDD severity with respect to depressive symptoms, especially
      regarding guilt and failure. Our findings suggest that the upregulation of DHEA-s
      may be a part of a compensatory process in very-mild-to-moderate depression, and
      the failure of this compensation mechanism may underlie the development of severe
      depression.

PMID- 28449565
TI  - Effect of Oxcarbazepine on Serum Brain Derived Neurotrophic Factor in Bipolar
      Mania: An Exploratory Study.
AB  - Objective: In bipolar disorder, serum brain-derived neurotrophic factor (BDNF)
      level decreases leading to dysfunctions of critical neurotrophic, cellular
      plasticity and neuroprotective processes. The present study was conducted to
      evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar
      mania. Methods: The present study is a prospective, interventional, open label
      clinical study conducted on 25 patients of bipolar mania and 25 healthy controls.
      Detailed history, clinical evaluation including Young Mania Rating Scale (YMRS)
      scoring and serum BDNF were assessed at baseline for all 50 subjects. The bipolar
      patients were prescribed tablet oxcarbazepine and followed up after 4 weeks for
      clinical evaluation and re-estimation of serum BDNF and YMRS scoring. Results:
      The serum BDNF level in bipolar manic patients were compared with healthy
      controls at baseline and results revealed that there is a significant reduction
      (p=0.002) in serum BDNF level in bipolar patients. At follow-up after 4 weeks,
      the mean change in serum BDNF in bipolar group who were on oxcarbazepine
      monotherapy was found statistically significant (p=0.02) in comparison to healthy
      controls. In bipolar group, the YMRS score and serum BDNF at baseline have an
      inverse relation(r=-0.59) whereas change of the YMRS score had a positive
      correlation (r=0.67) with the change of serum BDNF over 4 weeks. Conclusion: In
      bipolar mania serum BDNF level is low and it is found to be increased with short
      term monotherapy with oxcarbazepine.

PMID- 28449566
TI  - Dose Trends of Aripiprazole from 2004 to 2014 in Psychiatric Inpatients in Korea.
AB  - Objective: Although aripiprazole has been widely used to treat various
      psychiatric disorders, little is known about the adequate dosage for Asian
      patients in clinical practice. Hence, we evaluated the initial and maximum doses
      of aripiprazole from 2004 to 2014 to estimate the appropriate dosage for Korean
      psychiatric inpatients in clinical practice. Methods: In this retrospective
      study, we reviewed the medical records of patients who were hospitalized in five
      university hospitals in Korea from March 2004 to December 2014. The psychiatric
      diagnosis according to the text revision of the Diagnostic and Statistical Manual
      of Mental Disorders, 4th edition during index hospitalization and the initial and
      maximum doses of aripiprazole were evaluated. Results: There were 74 patients in
      Wave 1 (2004-2006), 201 patients in Wave 2 (2007-2010), and 353 patients in Wave
      3 (2011-2014). The initial doses of aripiprazole in all diagnostic groups were
      significantly lower in Wave 3 than in Wave 2. The maximum doses of aripiprazole
      in each diagnostic group were not significantly different among Waves 1, 2, and
      3. Conclusion: The relatively low initial doses of aripiprazole documented in our
      study may reflect a strategy by clinicians to minimize the side effects
      associated with aripiprazole use, such as akathisia.

PMID- 28449567
TI  - Dose Dependent Course of Hyperprolactinemic and Normoprolactinemic Galactorrhea
      Induced by Venlafaxine.
AB  - Venlafaxine is a serotonergic and noradrenergic reuptake inhibitor which is used
      for the treatment of depression. We report a case of galactorrhea in a patient
      with major depressive disorder after starting treatment with venlafaxine. In
      particular, we discuss the course of hyper and normoprolactinemic galactorrhea.
      We managed this side effect initially by dose reduction and further by switching
      to essitalopram. Physicians should be aware of endocrinologic side effects such
      as galactorrhea during the serotonin and noradrenaline reuptake inhibitor
      treatment.

PMID- 28449568
TI  - Bilateral Pretibial Edema Associated with Paliperidone Palmitate Long-acting
      Injectable: A Case Report.
AB  - Peripheral edema is observed as an adverse effect of the usage of antipsychotics
      in the literature. This case report describes a 36-year-old female patient with
      the diagnosis of paranoid schizophrenia who presented with pretibial edema
      following initiation of long-acting injectable paliperidone palmitate. Pretibial
      edema developed within the second week of treatment and completely disappeared
      after its discontinuation.

PMID- 28449569
TI  - Baclofen Abuse due to Its Hypomanic Effect in Patients with Alcohol Dependence
      and Comorbid Major Depressive Disorder.
AB  - Baclofen is a gamma-aminobutyric acid type B receptor agonist used as an anti
      craving agent for treatment of alcohol dependence. It has gained popularity in
      the recent times because it is well tolerated even in patients with hepatic
      impairments. Herein we are summarizing the latest literature about baclofen
      induced hypomania and are reporting a case of baclofen abuse because of its mood
      elevating property in a patient of alcohol dependence with comorbid major
      depressive disorder. Literature review and case study of a 36-year-old male with
      alcohol dependence with comorbid major depressive disorder was prescribed with
      tablet baclofen as an anti-craving agent along with antidepressant medicines. The
      patients who did not improve with conventional antidepressant therapy started
      feeling better in terms of his mood symptoms on taking tablet baclofen. Owing to
      the mood elevating property he started abusing baclofen. Despite its safety
      profile in hepatic impairment, one must be very cautious in prescribing baclofen
      because of its mood altering property which may account for its abuse
      potentiality.

PMID- 28449570
TI  - Low-dose Clozapine-induced Seizure: A Case Report.
AB  - Seizures are believed to be a dose-dependent side effect of clozapine. In this
      case report, we describe a patient who had tonic-clonic seizures after using a
      low dose clozapine who did not have any seizure risk. The 29-year-old male
      patient had been followed-up with a diagnosis of schizophrenia for about 5 years.
      When using clozapine 200 mg/day he had a tonic-clonic seizure with bilateral
      diffuse epileptic activity in electroencephalography (EEG). In the literature,
      there are a few case reports about low-dose clozapine-induced seizure. Seizures
      were observed in our case with a low dose of clozapine (200 mg/day) making this
      case remarkable. EEG monitoring at regular intervals and examination of plasma
      levels of clozapine could be useful in preventing the development of seizures.

PMID- 28449572
TI  - Early Augmentation Response with Low-frequency Repetitive Transcranial Magnetic
      Stimulation in Treatment Resistant Depression.

PMID- 28449571
TI  - Tardive Dyskinesia Associated with Bupropion.
AB  - Present report describes a 46 year old male patient with a diagnosis of major
      depression who developed tardive dyskinesia during bupropion therapy. Our patient
      had no history of neuroleptic use and his laboratory and neurologic examinations
      were normal. He had no family history of neurologic diseases. Although bupropion
      induced dyskinesia has been previously reported in the literature, it is rare and
      our case is the first case regarding tardive dyskinesia.

PMID- 28449573
TI  - A case of ruptured hepatic angiomyolipoma in a young male.
AB  - A 31-year-old male visited a local hospital due to sudden-onset severe abdominal
      pain. Abdominal computed tomography revealed a solid cystic mass with a size of
      approximately 12 cm and exhibiting both hemorrhage and fluid collection in the
      pelvic cavity. Emergency angiography and embolization were performed, and a large
      hepatic tumor was subsequently surgically resected. The tumor cells stained
      positive for human melanoma black-45 and smooth-muscle actin, and the pathologic
      diagnosis was hepatic angiomyolipoma. This case report also discusses the
      spontaneous rupture of a hepatic angiomyolipoma.

PMID- 28449574
TI  - The Clinical Utilization of Radiation Therapy in Korea between 2011 and 2015.
AB  - PURPOSE: The purpose of this study was to estimate the clinical utilization of
      radiation therapy (RT) in Korea between 2011 and 2015. MATERIALS AND METHODS: We
      analyzed the claims data from the Health Insurance Review and Assessment Service
      to estimate the clinical utilization of RT. The source population consisted of
      all patients who had any of the International Classification of Diseases 10th
      revision cancer diagnoses (C00-C97) and those with diagnostic codes D00-D48, who
      were also associated with at least one of the procedure codes related to RT.
      RESULTS: The total number of patients who received RT in 2011, 2012, 2013, 2014,
      and 2015 were 54,810, 59,435, 61,839, 64,062, and 66,183, respectively. Among
      them, the total numbers of male and female patients were 24,946/29,864 in 2011,
      27,211/32,224 in 2012, 28,111/33,728 in 2013, 29,312/34,750 in 2014, and
      30,266/35,917 in 2015. The utilization rate of RT in cancer patients has also
      increased steadily over the same period from 25% to 30%. The five cancers that
      were most frequently treated with RT between 2011 and 2012 were breast, lung,
      colorectal, liver, and uterine cervical cancers. However, the fifth most common
      cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate
      cancer. More than half of cancer patients (64%) were treated with RT in the
      capital area (Seoul, Gyeonggi, and Incheon). CONCLUSION: The total number of
      patients who underwent RT increased steadily from 2011 to 2015 in Korea. The
      utilization rate of RT in cancer patients is also increasing.

PMID- 28449575
TI  - Visualization of Endogenous ERK1/2 in Cells with a Bioorthogonal Covalent Probe.
AB  - The RAS-RAF-MEK-ERK pathway has been intensively studied in oncology, with RAS
      known to be mutated in ~30% of all human cancers. The recent emergence of ERK1/2
      inhibitors and their ongoing clinical investigation demands a better
      understanding of ERK1/2 behavior following small-molecule inhibition. Although
      fluorescent fusion proteins and fluorescent antibodies are well-established
      methods of visualizing proteins, we show that ERK1/2 can be visualized via a less
      invasive approach based on a two-step process using inverse electron demand Diels
      Alder cycloaddition. Our previously reported trans-cyclooctene-tagged covalent
      ERK1/2 inhibitor was used in a series of imaging experiments following a click
      reaction with a tetrazine-tagged fluorescent dye. Although limitations were
      encountered with this approach, endogenous ERK1/2 was successfully imaged in
      cells, and "on-target" staining was confirmed by over-expressing DUSP5, a nuclear
      ERK1/2 phosphatase that anchors ERK1/2 in the nucleus.

PMID- 28449576
TI  - Dissociative Recombination of Acetone Fragments, Adducts, and Dimer Ions.
AB  - The room temperature dissociative recombination of ions formed in an
      acetone/argon plasma has been studied using the flowing afterglow Langmuir probe
      mass spectrometer method. By changing the concentration of acetone density, it is
      possible to have a plasma dominated by different types of ions (fragments,
      adducts, and dimer ions). The application of these measurements to astrophysical
      plasmas is discussed.

PMID- 28449577
TI  - Cobalt-Catalyzed Asymmetric Hydroboration/Cyclization of 1,6-Enynes with
      Pinacolborane.
AB  - We report a cobalt-catalyzed asymmetric hydroboration/cyclization of 1,6-enynes
      with catalysts generated from Co(acac)2 and chiral bisphosphine ligands and
      activated in situ by reaction with pinacolborane (HBpin). A variety of oxygen-,
      nitrogen-, and carbon-tethered 1,6-enynes underwent this asymmetric
      transformation, yielding both alkyl- and vinyl-substituted boronate esters
      containing chiral tetrahydrofuran, cyclopentane, and pyrrolidine moieties with
      high to excellent enantioselectivities (86%-99% ee).

PMID- 28449578
TI  - Molybdenum Sulfide for Hydrogen Evolution Reaction: The Importance of Solution
      Dynamic Wetting Behavior in The Drying Process.
AB  - MoSx serving as a hydrogen evolution reaction electrocatalyst is known for its
      morphology sensitive characteristic. The low temperature thermo-decomposition
      method provides an easy and energy saving pathway to produce highly active MoSx
      on carbon paper substrates. However, during the precursor solution drying
      process, the dynamics of liquid wetting behavior dominates the morphology of the
      precursor salt and eventually the morphology of MoSx. As a result, here, for the
      first time, by carefully pairing the substrate hydrophobicity and solvent
      polarity, the cohesive force between solvent molecules and adhesive force between
      solvent and carbon substrate can be tuned, and thus the MoSx morphology can be
      controlled. Pairing hydrophilic carbon paper with DMF + H2O mixing solvent
      results in a relatively strong adhesive force, as a result, we are able to lower
      the overpotential required at the benchmark current density, 10 mA/cm2, to as low
      as 0.160 V and boost the current density to 40 mA/cm2 at -0.2 V vs RHE. This
      mainly results from the low charge transfer resistance and the well wrapped MoSx
      on carbon paper fiber structure. Furthermore, this well wrapped MoSx on
      hydrophilic carbon paper was proved to be comparably stable for constant voltage
      electrolysis operation.

PMID- 28449579
TI  - Enhanced Kinetics of Electrochemical Hydrogen Uptake and Release by Palladium
      Powders Modified by Electrochemical Atomic Layer Deposition.
AB  - Electrochemical atomic layer deposition (E-ALD) is a method for the formation of
      nanofilms of materials, one atomic layer at a time. It uses the galvanic exchange
      of a less noble metal, deposited using underpotential deposition (UPD), to
      produce an atomic layer of a more noble element by reduction of its ions. This
      process is referred to as surface limited redox replacement and can be repeated
      in a cycle to grow thicker deposits. It was previously performed on nanoparticles
      and planar substrates. In the present report, E-ALD is applied for coating a
      submicron-sized powder substrate, making use of a new flow cell design. E-ALD is
      used to coat a Pd powder substrate with different thicknesses of Rh by exchanging
      it for Cu UPD. Cyclic voltammetry and X-ray photoelectron spectroscopy indicate
      an increasing Rh coverage with increasing numbers of deposition cycles performed,
      in a manner consistent with the atomic layer deposition (ALD) mechanism. Cyclic
      voltammetry also indicated increased kinetics of H sorption and desorption in and
      out of the Pd powder with Rh present, relative to unmodified Pd.

PMID- 28449580
TI  - Catalytic Anti-Markovnikov Hydroallylation of Terminal and Functionalized
      Internal Alkynes: Synthesis of Skipped Dienes and Trisubstituted Alkenes.
AB  - We have developed catalytic anti-Markovnikov hydroallylation of terminal and
      functionalized internal alkynes. In this article, we describe the development of
      the reaction, exploration of the substrate scope, and a study of the reaction
      mechanism. Synthesis of skipped dienes through the hydroallylation of terminal
      alkyl and aryl alkynes with simple allyl phosphates and 2-substituted allyl
      phosphates is described. The hydroallylation of functionalized internal alkynes
      leads to the formation of skipped dienes containing trisubstituted alkenes. We
      demonstrate that the hydroallylation of internal alkynes can be used in the regio
      and diastereoselective synthesis of complex trisubstituted alkenes. A mechanism
      of the hydroallylation reaction is proposed, and experimental evidence is
      provided for the key steps of the catalytic cycle. Stoichiometric experiments
      demonstrate an unexpected role of lithium alkoxide in the carbon-carbon bond
      forming step of the reaction. A study of the hydrocupration of internal alkynes
      provides new insight into the structure, stability, and reactivity of alkenyl
      copper intermediates, as well as insight into the source of the regioselectivity
      in reactions of internal alkynes.

PMID- 28449584
TI  - Retention of poly(N-isopropylacrylamide) on 3-aminopropyltriethoxysilane.
AB  - Silane coupling agents are commonly employed to link an organic polymer to an
      inorganic substrate. One of the widely utilized coupling agents is 3
      aminopropyltriethoxy silane (APTES). In this study, the authors investigated the
      ability of APTES to retain thermo-responsive poly(N-isopropylacrylamide)
      (pNIPAAm) on hydroxylated surfaces such as glass. For comparison purposes, the
      authors also evaluated the retention behaviors of (1) polystyrene, which likely
      has weaker van der Waals interactions and acid-base interactions (contributed by
      hydrogen-bonding) with APTES, on APTES as well as (2) pNIPAAm on two other silane
      coupling agents, which have similar structures to APTES, but exhibit less
      interaction with pNIPAAm. Under our processing conditions, the stronger
      interactions, particularly hydrogen bonding, between pNIPAAm and APTES were found
      to contribute substantially to the retention of pNIPAAm on the APTES modified
      surface, especially on the cured APTES layer when the interpenetration was
      minimal or nonexistent. On the noncured APTES layer, the formation of an APTES
      pNIPAAm interpenetrating network resulted in the retention of thicker pNIPAAm
      films. As demonstrated by water contact angles [i.e., 7 degrees -15 degrees 
      higher at 40  degrees C, the temperature above the lower critical solution
      temperature (LCST) of 32  degrees C for pNIPAAm, as compared to those at 25 
      degrees C] and cell attachment and detachment behaviors (i.e., attached/spread at
      37  degrees C, above LCST; detached at 20  degrees C, below LCST), the retained
      pNIPAAm layer (6-15 nm), on both noncured and cured APTES, exhibited thermo
      responsive behavior. The results in this study illustrate the simplicity of using
      the coupling/adhesion promoting ability of APTES to retain pNIPAAm films on
      hydroxylated substrates, which exhibit faster cell sheet detachment (<=30 min) as
      compared to pNIPAAm brushes (in hours) prepared using tedious and costly grafting
      approaches. The use of adhesion promoters to retain pNIPAAm provides an
      affordable alternative to current thermo-responsive supports for cell sheet
      engineering and stem cell therapy applications.

PMID- 28449586
TI  - Liriopesides B inhibited cell growth and decreased CA125 level in human ovarian
      cancer A2780 cells.
AB  - To study the effect of liriopesides B on cell growth curve, cell doubling time,
      the activity of tumour marker CA125 and alkaline phosphatase (AKP) in human
      ovarian cancer A2780 cells. Both cell growth curve and doubling time were studied
      by MTT assay, CA125 level and AKP activity were determined by respective kits.
      Results showed that liriopesides B could shift down the A2780 cells growth curve
      in a dose-time-dependent manner and inhibit the proliferation in A2780 cells with
      the maximum inhibitory rate 94.462% at 120 h, the doubling time was prolonged
      too. CA125 level was decreased in a dose-dependent way as well as AKP activity.
      Liriopesides B exhibited potential anticancer activity against human ovarian
      cancer A2780 cells.

PMID- 28449585
TI  - Elevated Plasma Abeta42 in Cognitively Impaired Individuals Taking ACE Inhibitor
      Antihypertensives.
AB  - BACKGROUND/RATIONALE: Accumulating evidence suggests that the use of angiotensin
      converting enzyme inhibitor (ACE-I) medication protects against cognitive decline
      in the elderly patients. We investigated whether ACE-I use was associated with
      higher plasma levels of amyloid-beta (Abeta), possibly indicating improved Abeta
      clearance from brain to blood. METHODS: We measured and compared plasma
      concentrations of Abeta42, Abeta40, and creatinine in cognitively impaired
      individuals with amnestic mild cognitive impairment, probable Alzheimer's disease
      (AD) dementia, and mixed probable AD/vascular dementia. RESULTS: Plasma Abeta42
      levels and Abeta42/Abeta40 ratios of participants taking ACE-Is (n = 11)
      significantly exceeded ( t = 3.1, df = 19, P = .006; U = 24, P = .029,
      respectively) those not taking ACE-Is (n = 10). CONCLUSIONS: This study is the
      first to show an association between ACE-I use and increased plasma Abeta42 level
      and Abeta42/Abeta40 ratio in cognitively impaired individuals. Future
      investigations should assess whether a possible ACE-I-induced increase in plasma
      Abeta42 indicates improved Abeta42 clearance from brain that contributes to
      protection from cognitive decline.

PMID- 28449587
TI  - 'The dots just don't join up': Understanding the support needs of families of
      children on the autism spectrum.
AB  - Much research has documented the elevated levels of stress experienced by
      families of autistic children. Yet remarkably little research has examined the
      types of support that these families perceive to be beneficial to their lives.
      This study, co-produced by researchers and school-based professionals, sought to
      establish these families' support needs from their own perspectives. In total,
      139 parents of autistic children with additional intellectual disabilities and
      limited spoken communication, all attending an inner-city London school,
      participated in an initial survey examining parental wellbeing, self-efficacy and
      the extent to which they felt supported. Semi-structured interviews were
      conducted with a subgroup of parents ( n = 17), some of whom reported in the
      survey that they felt unsupported, in order to gain their in-depth perspectives.
      The results from both the survey and the interviews suggested that existing
      support (particularly from formal support services) was not meeting parents'
      needs, which ultimately made them feel isolated and alienated. Parents who were
      interviewed called for service provision that adopted a relational, family
      centred approach - one that understands the specific needs of the whole family,
      builds a close working relationship with them and ensures that they are supported
      at times when the parents and families feel they need it most.

PMID- 28449588
TI  - Disparities in HIV knowledge and attitudes toward biomedical interventions among
      the non-medical HIV workforce in the United States.
AB  - Non-medical, community-based workers play a critical role in supporting people
      living with (or at risk of acquiring) HIV along the care continuum. The
      biomedical nature of promising advances in HIV prevention, such as pre-exposure
      prophylaxis and treatment-as-prevention, requires frontline workers to be
      knowledgeable about HIV science and treatment. This study was developed to:
      measure knowledge of HIV science and treatment within the HIV non-medical
      workforce, evaluate workers' familiarity with and attitudes toward recent
      biomedical interventions, and identify factors that may affect HIV knowledge and
      attitudes. A 62-question, web-based survey was completed in English or Spanish
      between 2012 and 2014 by 3663 US-based employees, contractors, and volunteers
      working in AIDS service organizations, state/local health departments, and other
      community-based organizations in a non-medical capacity. Survey items captured
      the following: respondent demographics, HIV science and treatment knowledge, and
      familiarity with and attitudes toward biomedical interventions. An average of 61%
      of HIV knowledge questions were answered correctly. Higher knowledge scores were
      associated with higher education levels, work at organizations that serve people
      living with HIV/AIDS or who are at a high risk of acquiring HIV, and longer
      tenure in the field. Lower knowledge scores were associated with non-Hispanic
      Black or Black race/ethnicity and taking the survey in Spanish. Similarly,
      subgroup analyses showed that respondents who were non-Hispanic Black or Hispanic
      (versus non-Hispanic white), as well as those located in the South (versus other
      regions) scored significantly lower. These subpopulations were also less familiar
      with and had less positive attitudes toward newer biomedical prevention
      interventions. Respondents who took the survey in Spanish (versus English) had
      lower knowledge scores and higher familiarity with, but generally less positive
      attitudes toward, biomedical interventions. In summary, low knowledge scores
      suggest the need for additional capacity-building efforts and training for non
      medical HIV workers, particularly those who provide services in the communities
      most affected by HIV.

PMID- 28449589
TI  - Colocated Mental Health/Developmental Care.
AB  - The inadequacy of mental health and developmental services for children is a
      widely recognized and growing problem. Although a variety of solutions have been
      proposed, none has been generally successful or feasible. This research describes
      models of colocation that have evolved in primary care settings in Massachusetts
      and reports on pediatricians' and their colocated colleagues' impressions of
      their benefits and challenges. Pediatricians in 18 practices that included a
      colocated mental health/developmental specialist (MH/DS) were identified through
      a survey administered through the state American Academy of Pediatrics Chapter,
      and interviewed. Practices varied widely in the professional expertise/training
      and roles of the MH/DSs, communication among providers, and financial
      arrangements. The majority of pediatricians and MH/DSs reported being pleased
      with their colocated arrangements, despite the costs rarely being supported by
      billing revenues. This study suggests that further development of such systems
      hold promise to meet the growing need for accessible pediatric mental and
      developmental health care.

PMID- 28449591
TI  - A Psychoevolutionary Approach to Identifying Preferred Nature Scenes With
      Potential to Provide Restoration From Stress.
AB  - BACKGROUND: Research supports therapeutic use of nature scenes in healthcare
      settings, particularly to reduce stress. However, limited literature is available
      to provide a cohesive guide for selecting scenes that may provide optimal
      therapeutic effect. OBJECTIVE: This study produced and tested a replicable
      process for selecting nature scenes with therapeutic potential.
      Psychoevolutionary theory informed the construction of the Importance for
      Survival Scale (IFSS), and its usefulness for identifying scenes that people
      generally prefer to view and that hold potential to reduce stress was tested.
      METHODS: Relationships between Importance for Survival (IFS), preference, and
      restoration were tested. General community participants ( N = 20 males, 20
      females; M age = 48 years) Q-sorted sets of landscape photographs (preranked by
      the researcher in terms of IFS using the IFSS) from most to least preferred, and
      then completed the Short-Version Revised Restoration Scale in response to viewing
      a selection of the scenes. RESULTS: Results showed significant positive
      relationships between IFS and each of scene preference (large effect), and
      restoration potential (medium effect), as well as between scene preference and
      restoration potential across the levels of IFS (medium effect), and for
      individual participants and scenes (large effect). CONCLUSIONS: IFS was supported
      as a framework for identifying nature scenes that people will generally prefer to
      view and that hold potential for restoration from emotional distress; however,
      greater therapeutic potential may be expected when people can choose which of the
      scenes they would prefer to view. Evidence for the effectiveness of the IFSS was
      produced.

PMID- 28449590
TI  - Continuous Glucose Monitoring in Older Adults With Type 1 and Type 2 Diabetes
      Using Multiple Daily Injections of Insulin: Results From the DIAMOND Trial.
AB  - OBJECTIVE: The objective was to determine the effectiveness of real-time
      continuous glucose monitoring (CGM) in adults >= 60 years of age with type 1
      (T1D) or type 2 (T2D) diabetes using multiple daily insulin injections (MDI).
      METHODS: A multicenter, randomized trial was conducted in the United States and
      Canada in which 116 individuals >=60 years (mean 67 +/- 5 years) with T1D (n =
      34) or T2D (n = 82) using MDI therapy were randomly assigned to either CGM
      (DexcomTM G4 Platinum CGM System(r) with software 505; n = 63) or continued
      management with self-monitoring blood glucose (SMBG; n = 53). Median diabetes
      duration was 21 (14, 30) years and mean baseline HbA1c was 8.5 +/- 0.6%. The
      primary outcome, HbA1c at 24 weeks, was obtained for 114 (98%) participants.
      RESULTS: HbA1c reduction from baseline to 24 weeks was greater in the CGM group
      than Control group (-0.9 +/- 0.7% versus -0.5 +/- 0.7%, adjusted difference in
      mean change was -0.4 +/- 0.1%, P < .001). CGM-measured time >250 mg/dL ( P =
      .006) and glycemic variability ( P = .02) were lower in the CGM group. Among the
      61 in the CGM group completing the trial, 97% used CGM >= 6 days/week in month 6.
      There were no severe hypoglycemic or diabetic ketoacidosis events in either
      group. CONCLUSION: In adults >= 60 years of age with T1D and T2D using MDI, CGM
      use was high and associated with improved HbA1c and reduced glycemic variability.
      Therefore, CGM should be considered for older adults with diabetes using MDI.

PMID- 28449592
TI  - "I had to change so much in my life to live with my new limitations": Multimorbid
      patients' descriptions of their most bothersome chronic conditions.
AB  - Objective To characterize diseases that are described as most bothersome by
      individuals with multiple chronic conditions and to identify themes that
      characterize their experiences with their most bothersome condition. Methods In a
      survey of patients at an academic center and a Veterans Affairs hospital, we
      asked individuals with multiple chronic conditions to identify their most
      bothersome chronic condition and describe why it is challenging. Standard content
      analysis methods were used to code responses and identify themes reflecting
      characteristics of most bothersome conditions. Results The most commonly cited
      bothersome conditions were chronic pain (52%), diabetes (43%), post-traumatic
      stress disorder (25%), heart failure (24%), and lung problems (20%). Conditions
      were described as most bothersome due to: (a) impact on function and quality of
      life (e.g. active symptoms, activity limitations), (b) health consequences or
      sequelae (e.g. risk of complications), and (c) challenges associated with
      treatment or self-management. Patterns of theme dominance varied for conditions
      with different characteristics. Discussion The conditions that patients with
      multiple chronic conditions identify as most bothersome vary depending on
      individuals' diseases and their health-related preferences and priorities.
      Ascertaining patients' most bothersome conditions and associated challenges,
      stress, and frustrations may help ensure that management decisions are aligned
      with patient preferences and priorities.

PMID- 28449593
TI  - Montessori-based activities among persons with late-stage dementia: Evaluation of
      mental and behavioral health outcomes.
AB  - Objectives Literature regarding Montessori-based activities with older adults
      with dementia is fairly common with early stages of dementia. Conversely,
      research on said activities with individuals experiencing late-stage dementia is
      limited because of logistical difficulties in sampling and data collection. Given
      the need to understand risks and benefits of treatments for individuals with late
      stage dementia, specifically regarding their mental and behavioral health, this
      study sought to evaluate the effects of a Montessori-based activity program
      implemented in a long-term care facility. Method Utilizing an interrupted time
      series design, trained staff completed observation-based measures for 43
      residents with late-stage dementia at three intervals over six months. Empirical
      measures assessed mental health (anxiety, psychological well-being, quality of
      life) and behavioral health (problem behaviors, social engagement, capacity for
      activities of daily living). Results Group differences were observed via repeated
      measures ANOVA and paired-samples t-tests. The aggregate, longitudinal results
      from baseline to final data interval-for the psychological and behavioral health
      measures were as follows: problem behaviors diminished though not significantly;
      social engagement decreased significantly; capacities for activities of daily
      living decreased significantly; quality of life increased slightly but not
      significantly; anxiety decreased slightly but not significantly; and
      psychological well-being significantly decreased. Conclusion Improvements
      observed for quality of life and problem behaviors may yield promise for
      Montessori-based activities and related health care practices. The rapid
      physiological and cognitive deterioration from late-stage dementia should be
      considered when interpreting these results.

PMID- 28449594
TI  - Admiral Nurses delivering workplace clinics for family carers: Innovative
      practice.
AB  - Dementia UK and The Charity for Civil Servants teamed up to test the
      acceptability and feasibility of delivering a work-based Admiral Nurse clinic to
      support family carers during their employed working hours. This paper presents
      some of the learning from this innovative approach.

PMID- 28449595
TI  - Pharmaceutical Perspectives of Spices and Condiments as Alternative Antimicrobial
      Remedy.
AB  - Medicinal values of spices and condiments are being revived by biologists through
      in vitro and in vivo trials providing evidence for its antimicrobial activities.
      The essential oils and extracts of spices like black pepper, cloves, cinnamon,
      and nutmeg contain active compounds like piperine, eugenol, cinnamaldehyde, and
      lignans. Similarly, condiments like coriander, black cumin, turmeric, garlic, and
      ginger are recognized for constituents like linalool, thymoquinones, curcumin,
      allicin, and geranial respectively. These act as natural preventive components of
      several diseases and represent as antioxidants in body cells. Scientists have to
      investigate the biochemical nature, mode of action, and minimum concentration of
      administrating active ingredients effectively. This review reports findings of
      recent research carried out across South Asia and Middle East countries where
      spices and condiments form chief flavoring components of traditional foods. It
      narrates the history, myths, and facts people believe in these regions. There may
      not be scientific explanation but has evidence of cure for centuries.

PMID- 28449596
TI  - Changes in Platelet Count and Size Indices in Adolescent Patients With Anorexia
      Nervosa.
AB  - The significance of platelet size indices has not been widely analyzed in
      anorexia nervosa (AN). It seems important to get more knowledge on the easily
      available indices of platelet function obtained by routine complete blood count
      analysis in patients with AN. We analyzed platelet count (PLT), platelet
      distribution width (PDW), and mean platelet volume using an automated blood cell
      counter in 25 females with AN and healthy age- and gender-matched nonatopic
      controls. Mean PLT was significantly lower in patients with AN than in the
      control group. Platelet distribution width values in patients with AN were
      significantly higher than those in the controls. Platelet distribution width
      values significantly correlated with the disease duration and rate of body weight
      loss in the anorectic patients. Anorexia nervosa in adolescents is associated
      with a decrease in PLT along with an increased PDW, which may be an indicator of
      dysregulated thrombopoiesis.

PMID- 28449597
TI  - Assessment of hearing aid algorithms using a master hearing aid: the influence of
      hearing aid experience on the relationship between speech recognition and
      cognitive capacity.
AB  - OBJECTIVES: Model-based hearing aid development considers the assessment of
      speech recognition using a master hearing aid (MHA). It is known that aided
      speech recognition in noise is related to cognitive factors such as working
      memory capacity (WMC). This relationship might be mediated by hearing aid
      experience (HAE). The aim of this study was to examine the relationship of WMC
      and speech recognition with a MHA for listeners with different HAE. DESIGN: Using
      the MHA, unaided and aided 80% speech recognition thresholds in noise were
      determined. Individual WMC capacity was assed using the Verbal Learning and
      Memory Test (VLMT) and the Reading Span Test (RST). STUDY SAMPLE: Forty-nine
      hearing aid users with mild to moderate sensorineural hearing loss divided into
      three groups differing in HAE. RESULTS: Whereas unaided speech recognition did
      not show a significant relationship with WMC, a significant correlation could be
      observed between WMC and aided speech recognition. However, this only applied to
      listeners with HAE of up to approximately three years, and a consistent weakening
      of the correlation could be observed with more experience. CONCLUSIONS: Speech
      recognition scores obtained in acute experiments with an MHA are less influenced
      by individual cognitive capacity when experienced HA users are taken into
      account.

PMID- 28449598
TI  - Using GRADE as a framework to guide research on the sexual and reproductive
      health and rights (SRHR) of women living with HIV - methodological opportunities
      and challenges.
AB  - In March 2016, WHO reviewed evidence to develop global recommendations on the
      sexual and reproductive health and rights (SRHR) of women living with HIV.
      Systematic reviews and a global survey of women living with HIV informed the
      guideline development decision-making process. New recommendations covered
      abortion, Caesarean section, safe disclosure, and empowerment and self-efficacy
      interventions. Identification of key research gaps is part of the WHO guidelines
      development process, but consistent methods to do so are lacking. Our method
      aimed to ensure consistency and comprised the systematic application of a
      framework based on GRADE (Grading of Recommendations, Assessment, Development and
      Evaluation) to the process. The framework incorporates the strength and quality
      rating of recommendations and the priorities reported by women in the survey to
      inform research prioritisation. For each gap, we also articulated: (1) the most
      appropriate and robust study design to answer the question; (2) alternative
      pragmatic designs if the ideal design is not feasible; and (3) the methodological
      challenges facing researchers through identifying potential biases. We found 12
      research gaps and identified five appropriate study designs to address the
      related questions: (1) Cross-sectional surveys; (2) Qualitative interview-driven
      studies; (3) Registries; (4) Randomised controlled trials; and (5) Medical record
      audit. Methodological challenges included selection, recruitment,
      misclassification, measurement and contextual biases, and confounding. In
      conclusion, a framework based on GRADE can provide a systematic approach to
      identifying research gaps from a WHO guideline. Incorporation of the priorities
      of women living with HIV into the framework systematically ensures that women
      living with HIV can shape future policy decisions affecting their lives.
      Implementation science and participatory research are appropriate over-arching
      approaches to enhance uptake of interventions and to ensure inclusion of women
      living with HIV at all stages of the research process.

PMID- 28449599
TI  - An explanatory factor analysis of a brief self-report scale to detect
      neurocognitive impairment among HIV-positive men who have sex with men and
      transgender women in Peru.
AB  - Neurocognitive impairment (NCI) has been associated with poor clinical outcomes
      in various patient populations. This study used exploratory factor analysis (EFA)
      to examine the factor structure of the existing 95-item Neuropsychological
      Impairment Scale (NIS) to create a suitable NCI screening instrument for people
      living with HIV (PLH). In Lima, Peru, 313 HIV-positive men who have sex with men
      (MSM) and transgender women (TGW) prescribed antiretroviral therapy (ART)
      completed the NIS using computer-assisted self-interviews (CASI). The EFA used
      principal axis factoring and orthogonal varimax rotation, which resulted in 42
      items with an 8-factor solution that explained 51.8% of the overall variance. The
      revised, 8-factor, Brief Inventory of Neurocognitive Impairment for Peru (BINI-P)
      showed a diverse set of factors with excellent to good reliability (i.e., F1
      alpha = 0.92 to F8 alpha = 0.78). This EFA supports the use of the BINI-P to
      screen for NCI among Spanish-speaking, HIV-positive MSM and TGW. Future research
      should examine the effectiveness of the BINI-P in detecting NCI in clinical care
      settings and the impact of NCI on HIV health-related outcomes, including linkage
      and retention in care, ART adherence and HIV risk behaviors.

PMID- 28449600
TI  - Comparison of phenolic acids and flavonoids contents in various cultivars and
      parts of common lavender (Lavandula angustifolia) derived from Poland.
AB  - The aim of study was to compare the content of phenolic acids and flavonoids in
      two cultivars of Lavandula angustifolia: 'Blue River' and 'Ellagance Purple',
      including flowers and leafy stalks. Total phenolics and total flavonoids contents
      were determined by UV-Vis spectroscopy. The contents of total phenolics in leafy
      stalks (3.71-4.06 mg g-1 d.m.) were higher than in flowers (1.13-1.14 mg g-1
      d.m.). Similarly, higher total contents of flavonoids were determined in leafy
      stalks (3.41-3.51 mg g-1 d.m.), as compared with flowers (0.86-0.91 mg g-1 d.m.).
      Phenolic acids and flavonoids were identified and quantified using HPLC and UPLC
      methods. Three phenolic acids were determined: rosmarinic, ferulic and caffeic
      acid. Lavender extracts contained also flavonoids from group of apigenin,
      luteolin and quercetin. Higher amounts of luteolin diglucuronide and luteolin
      glucuronide were found in leafy stalks in comparison to flowers. Obtained results
      indicate that leafy stalks of lavender can be also valuable source of antioxidant
      compounds.

PMID- 28449601
TI  - Random Versus Blocked Practice to Enhance Mental Representation in Golf Putting.
AB  - The purpose of this study was to investigate changes in mental representation
      from either random or blocked practice when engaged in golf putting. Thirty
      participants were randomly assigned to random practice, blocked practice, and no
      practice groups. First, we measured novice golfers' initial mental representation
      levels and required them to perform 18 putting trials as a pre-test. We then
      asked random and blocked groups to practice in accordance with their group
      assignment for six consecutive days (10 blocks each day, 18 trials each). A week
      after the last practice session, we re-measured all participants' final mental
      representation levels and required them to perform 18 putting trials to evaluate
      learning retention through practice. While those engaged in the random practice
      method putted more poorly during acquisition (i.e., practice) than those in
      blocked practice, the random practice group experienced more accurate retention
      during the final putting trials, and they showed a more structured mental
      representation than those in blocked practice, one that was more similar to that
      of skilled golfers. These results support the acquisition of a rich mental
      representation through random versus blocked practice.

PMID- 28449602
TI  - Reference values for B-cell surface markers and co-receptors associated with
      primary immune deficiencies in healthy Turkish children.
AB  - In order to evaluate B-lymphocyte subsets of patients with primary
      immunodeficiencies, the normal values for national healthy children have to be
      used as a reference. Recently, B-cell co-receptor markers (CD19, CD21, and CD81)
      and CD20, CD22, and CD27 deficiencies have been reported in relation with
      different primary immunodeficiency diseases. The objective of this study was to
      establish national reference values for B-lymphocyte co-receptors and some
      surface markers, CD20, CD22, CD27, as well as classic lymphocyte subsets in the
      peripheral blood of healthy children. A total of 90 healthy children were
      included in this study. Complete blood counts were performed and cells with CD3,
      CD4, CD8, CD19, CD16/56, CD20, CD21, CD22, CD27, and CD81 surface markers were
      simultaneously detected by flow cytometry. The children were evaluated in three
      age subgroups, 0-1, 1-6, and >6 years, and minimum, maximum, mean, mean minus
      standard deviation, and 2.5-97.5 percentile values were all determined. By
      establishing reliable reference ranges for these surface markers, we hoped to
      help identifying and classifying some primary immunodeficiency patients,
      especially those defined as unclassified hypogammaglobulinemia and those without
      definite diagnosis.

PMID- 28449603
TI  - Differential regulation of surface receptor expression, proliferation, and
      apoptosis in HaCaT cells stimulated with interferon-gamma, interleukin-4, tumor
      necrosis factor-alpha, or muramyl dipeptide.
AB  - Keratinocytes are routinely subjected to both internal and external stimulation.
      This study investigates the effects of interferon gamma, interleukin-4, tumor
      necrosis factor alpha, and the synthetic immunomodulator muramyl dipeptide on the
      human keratinocyte cell line, HaCaT. Following HaCaT stimulation with cytokines
      or muramyl dipeptide for different time periods, changes in the expression of
      different cell surface receptors, cell proliferation, and cell apoptosis were
      evaluated by flow cytometry, tritiated thymidine uptake, and annexin-V staining,
      respectively. A significant decrease in the expression of CD49d was found upon
      treatment with interleukin-4. Interferon gamma and tumor necrosis factor alpha
      increased the expression of intercellular adhesion molecule 1 and major
      histocompatibility complex class I, whereas major histocompatibility complex
      class II and CD1b were only upregulated by interferon gamma. Interferon gamma and
      tumor necrosis factor alpha had opposite effects regarding CD119 expression, with
      the former downregulating, while the latter upregulating its expression. Of the
      stimuli tested, only interferon gamma and tumor necrosis factor alpha
      significantly inhibited proliferation of HaCaT cells, yet only interferon gamma
      played a significant role in inducing HaCaT cell apoptosis. Our data demonstrate
      differential effects of the three tested cytokines on keratinocytes and reveal
      that the absence of HaCaT cell responses to muramyl dipeptide is associated with
      undetectable levels of its cytoplasmic receptor, nucleotide-binding
      oligomerization domain-containing protein 2.

PMID- 28449604
TI  - Retriever first embolectomy (ReFirE): An alternative approach for challenging
      cervical access.
AB  - After endovascular treatment became the standard of care procedure for acute
      ischaemic stroke with large artery occlusion in 2015 the number of performed
      interventions has increased dramatically. Especially because age is no exclusion
      criterion for endovascular treatment, a relevant number of patients with
      difficult to access carotid arteries has to be treated. In these patients a
      direct puncture of the carotid is a valuable tool but is associated with severe
      complications and an initial learning curve. We therefore developed the so called
      retriever first embolectomy (ReFirE) technique in which a stentretriever is
      deployed over a 5F diagnostic catheter and a microcatheter to establish a stable
      anchor prior to accessing the internal carotid artery/intracranial vasculature
      with an 8F guide catheter and a 5F/6F intermediate catheter. We hereby report the
      first case in which we performed a thrombectomy applying our novel technique.

PMID- 28449605
TI  - Precarious Employment and Quality of Employment in Relation to Health and Well
      being in Europe.
AB  - This article presents an overview of the recent work on precarious employment and
      employment quality in relation to workers' health and well-being. More
      specifically, the article mainly reviews the work performed in the E.U. 7th
      Framework project, SOPHIE. First, we present our overarching conceptual
      framework. Then, we provide a compiled overview of the evidence on the
      sociodemographic and European cross-country distribution of employment quality
      and employment precariousness. Subsequently, we provide the current evidence
      regarding the relations with health and broader worker well-being indicators. A
      final section summarizes current insights on the pathways relating precarious
      employment and health and well-being. The article concludes with a plea for
      further data collection and research into the longitudinal effects of employment
      precariousness among emerging groups of workers. Based on the evidence compiled
      in this article, policymakers should be convinced of the harmful health and well
      being effects of employment precariousness and (further) labor market
      flexibilization.

PMID- 28449606
TI  - Pseudomyxoma Peritonei as a First Manifestation of KRAS-Mutated Urachal Mucinous
      Cystadenocarcinoma of the Bladder: A Case Report.
AB  - Only 28 cases of pseudomyxoma peritonei (PMP) arising from urachal neoplasms have
      been reported. We report one example of this extremely rare disease with KRAS
      mutational status in its spectrum of pathology. A 45-year-old woman presented
      with urachal frankly invasive mucinous cystadenocarcinoma confined to the dome of
      the bladder, which clinically manifested as PMP and was not detected at the first
      surgery. The primary tumour was revealed 6 months later because of its recurrence
      as PMP. Microscopic investigation revealed tubular adenoma and cystadenocarcinoma
      communicating with the bladder lumen and transitioning from the urachal
      urothelium to the mucinous epithelium. A urachal remnant was identified near the
      neoplasm. On immunohistochemistry, the tumour proved positive for CK7, CK20, CEA,
      and CDX2. Staining for beta-catenin revealed expression in both the cytoplasm and
      cell membrane. Mismatch repair protein expression was normal. Somatic KRAS
      mutation (G12V) was revealed in tubular adenoma, cystadenocarcinoma, and mucinous
      carcinoma peritonei and may play an oncogenic role in the malignant
      transformation of urachal mucosa and the development of PMP.

PMID- 28449607
TI  - Adenocarcinoma Ex-Goblet Cell Carcinoid of the Appendix With Metastatic
      Peritoneal Spread to Meckel's Diverticulum and Endometriosis.
AB  - Adenocarcinoma ex-goblet cell carcinoid is a very rare and histologically unique
      appendiceal malignancy with dual glandular and neuroendocrine differentiation.
      There is a high incidence of this tumor among middle-aged women with metastasis
      to the gynecologic tract with the mode of metastasis following peritoneal spread
      rather than hematogenous distribution. Adenocarcinoma ex-goblet cell carcinoid
      can spread to any peritoneal site including ovaries or omentum. We report a 37
      year-old healthy woman who initially presented with right lower quadrant
      abdominal pain and pseudomyxoma peritonei. Histopathology of the appendectomy
      specimen revealed an adenocarcinoma ex-goblet cell carcinoid, signet ring cell
      type. Follow-up right hemicolectomy, omentectomy, bilateral salpingo
      oophorectomy, and regional peritoneal resections revealed metastatic involvement
      by adenocarcinoma ex-goblet cell carcinoid, signet ring cell type. In this
      report, we describe a case of appendiceal adenocarcinoma ex goblet cell carcinoid
      with metastases to Meckel's diverticulum and areas of pelvic endometriosis, which
      have not been previously reported.

PMID- 28449608
TI  - Primary Pulmonary Myxoid Sarcoma: A Newly Described Entity-Report of a Case and
      Review of the Literature.
AB  - Primary pulmonary myxoid sarcoma (PPMS) is a recently described, exceedingly rare
      low-grade lung sarcoma that tends to present in young females as an endobronchial
      mass and shows evidence of an EWSR1- CREB1 fusion. Herein, we present a case of
      PPMS with fluorescence in situ hybridization (FISH) analysis for EWSR1 and CREB1
      rearrangements. An 80-year-old woman presented with an endobronchial,
      multinodular tumor exhibiting spindle, ovoid and epithelioid cells arranged in
      reticular/lattice-like and alveolar-like patterns in a myxoid background. The
      tumor showed focal epithelial membrane antigen immunoreactivity as well as an
      Alcian blue-positive stroma that was sensitive to digestion with hyaluronidase.
      EWSR1 and CREB1 rearrangements were detected by break-apart FISH probes. The
      patient showed persistence of disease 36 months after diagnosis and was
      discharged to hospice care. We contribute with a report of an additional case of
      this very unusual entity and perform a brief review of the literature published
      so far on the subject.

PMID- 28449609
TI  - Using children as standardized patients in OSCE in pediatric occupational
      therapy.
AB  - BACKGROUND: Objective structured clinical examinations (OSCEs) have been
      administered in physical and psychiatric occupational therapy (OT) education, but
      not in pediatric OT education. The objectives were to examine the satisfaction
      and the influences of OSCE in pediatric OT on all participants. METHODS: The OSCE
      contained evaluation, intervention, and parent education stations. Sixty
      examinees, 44 child standardized patients (SPs), 44 chaperones, three playroom
      managers, 14 OSCE assistants, and 15 examiners participated in the OSCE. An OSCE
      video and three playrooms were prepared for child SPs. RESULTS: Ninety percent of
      the child SPs liked taking part in the OSCE and 75-85% expressed interest in
      participating in an OSCE the following year. Their parents appreciated the
      chaperones accompanying their children and giving them a memorable day. 88.3% of
      the examinees thought that the OSCE was helpful for their upcoming clinical
      training. 73.3% preferred the OSCE over the written exam. 60-93.4% considered the
      implementation appropriate. Most of the examiners thought that the content (80
      100%) and the implementation (93.3-100%) were appropriate. Many chaperones
      reported having valuable experiences. CONCLUSIONS: It is practical using child
      SPs in OSCE in pediatric OT. The OSCE was beneficial to all participants. It is
      recommended that OSCEs be included in pediatric OT education.

PMID- 28449610
TI  - Using Twitter to increase content dissemination and control educational content
      with Presenter Initiated and Generated Live Educational Tweets (PIGLETs).
AB  - Live-tweeting during educational presentations is typically learner-generated and
      can lead to misquoted information. Presenter curated tweets have not been well
      described. We created Presenter Initiated and Generated Live Educational Tweets
      (PIGLETs) with the goal to broaden the reach of educational conferences. We
      hypothesized that using PIGLETs would increase the reach and exposure of our
      material. We developed a prospective single-arm intervention study performed
      during the "Not Another Boring Lecture" workshops presented at two national
      conferences in 2015. Presenters tweeted PIGLETs linked to unique hashtags
      #NotAnotherBoringLecture and #InnovateMedEd. Analytic software was used to
      measure the following outcomes: (1) number of tweets published by presenters
      versus learners, (2) reach (users exposed to content containing the hashtag), and
      (3) exposure (total number of times content was delivered). One hundred and
      twenty-six participants attended the workshops. A total of 636 tweets (including
      retweets) were sent by presenters containing the study hashtags, compared with
      162 sent by learners. #NotAnotherBoringLecture reached 47,200 users and generated
      136,400 impressions; #InnovateMedEd reached 36,400 users and generated 79,100
      impressions. PIGLETs allowed presenters to reach a significant number of
      learners, as well as control the content delivered through Twitter. PIGLETs can
      be used to augment educational sessions beyond the physical confines of the
      classroom.

PMID- 28449611
TI  - Return to play and performance after anterior cruciate ligament reconstruction in
      the National Basketball Association: surgeon case series and literature review.
AB  - OBJECTIVES: To investigate return to play (RTP) and functional performance after
      anterior cruciate ligament reconstruction (ACLR) in National Basketball
      Association (NBA) players and to perform a systematic review of the literature to
      understand RTP after ACLR in professional basketball. METHODS: NBA players
      undergoing ACLR between 2008 and 2014 by two surgeons were identified. RTP and
      performance were assessed based on a review of publically available statistics. A
      systematic review of the literature was performed using the MEDLINE database.
      Inclusion criteria were: English language, ACL surgery outcome, professional
      basketball and RTP outcome. We reviewed studies for RTP rates and RTP
      performance. RESULTS: Our study included 12 professional basketball players with
      NBA level experience. Eleven of the 12 players returned to their prior level of
      play. Eight of the 9 (88.9%) players actively playing in the NBA returned to play
      in the NBA at a mean 9.8 months. Among players returning to NBA play, during RTP
      season 1, mean per game statistics decreased for the following: minutes, points,
      rebounds, assists, steals, blocks, turnovers and personal fouls - none of these
      changes reached statistical significance. Player efficiency ratings significantly
      declined from pre-injury (12.5) to the first RTP season (7.6) (p = 0.05). By RTP
      season 2, player performance metrics approximated pre-injury levels and were not
      significantly different. Six studies met inclusion criteria; reported RTP rates
      ranged from 78-86%. Identified studies similarly found a decline in functional
      performance after RTP. CONCLUSION: There is a high rate (89%) of return to NBA
      play for NBA players undergoing ACLR. After RTP, however, there is a quantitative
      decline in initial season 1 RTP statistics with a significant decrease in player
      efficiency rating. By RTP season 2, performance metrics demonstrated an
      improvement compared to RTP season 1 but did not reach pre-injury functional
      performance, though performance metrics are not significantly different between
      pre-injury and RTP season 2.

PMID- 28449612
TI  - Residents' responsibilities: Adopting a wider view.
AB  - Current ACGME regulations have limited residents' weekly hours and continuous
      working hours, a marked change, despite its uncertain effects on physician well
      being and quality of care. Although residency programs in internal medicine and
      family medicine have adapted schedules to conform to these regulations,
      increasing evidence is accumulating to suggest that these training experiences
      are not adequately preparing the next generation of practicing primary care and
      hospital-based physicians. Data from an array of sources continue to demonstrate
      significant deficiencies in six areas of residents' responsibilities towards
      their patients: diminished patient "face time" and direct patient care; focus on
      patients' "reason for hospitalization" or "reason for visit" at the expense of
      possible neglect of patients' "secondary" medical problems; limited attention to
      patients' emotional or contextual problems and limited empathy; deficient
      implementation of the essential constituents of patient-centered care; neglect of
      habitual "reflective practice"; and excessive distinction between inpatient and
      outpatient responsibilities, leading to missed opportunities for inpatient
      residents to be aware of and attend to patients' post-discharge course although
      new information and readmissions related to the index hospitalization are
      prevalent. Thus, redesigning residency programs to widen residents' outlook and
      cover these inseparable components of high-quality care, may infuse the often
      fatigued and burnt-out residents with purpose and fulfillment, finally
      incorporating the missing elements of patient-centered care as integral parts of
      patients' admissions and therefore, of physicians' future careers.

PMID- 28449613
TI  - Emotion recognition and theory of mind in schizophrenia: A meta-analysis of
      neuroimaging studies.
AB  - OBJECTIVES: Patients with schizophrenia have difficulties processing the
      emotional and cognitive states of others. Neuroimaging studies show inconsistent
      findings. METHODS: We used a Seed-based d Mapping meta-analytic method to explore
      brain activation during facial emotion recognition and theory of mind tasks in
      schizophrenia patients. RESULTS: The patients showed lesser recruitment of the
      facial emotion processing network; behavioural performance was associated with
      the activation of the precentral gyrus. We found abnormal activation of the
      mentalising network in schizophrenia patients during reasoning about other
      people's mental states; patients with worse performances showed lesser activation
      in the right insula and superior temporal gyrus. Multimodal meta-analysis showed
      overlaps of brain-related abnormalities for both modalities in schizophrenia,
      with reduced recruitment of the right insula, anterior cingulate and medial
      prefrontal cortex and increased activation in the bilateral parietal cortex. Meta
      regression results indicate that illness duration, medication and symptomatology
      might influence social-cognitive network disruptions in schizophrenia.
      CONCLUSIONS: These findings suggest the complex impairment of social cognition,
      as demonstrated by neural-related circuit disruptions during facial emotion
      processing and theory of mind tasks in schizophrenia.

PMID- 28449614
TI  - Poly(lactic-co-glycolic acid) nanoparticles for sustained release of allyl
      isothiocyanate: characterization, in vitro release and biological activity.
AB  - The objective of this study is to establish the ability of entrap allyl
      isothiocyanate (AITC) into polymeric nanoparticles to extend its shelf life and
      enhance its antiproliferative properties. Natural compounds, such as AITC, have
      showed multi-targeting activity resulting in a wide-range spectrum of therapeutic
      properties in chronic and degenerative diseases, conversely with most current
      pharmaceutical drugs showing single targeting activity and often result in drug
      resistance after extended administration periods. Apparently, AITC-loaded
      poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) reduced AITC degradation
      and volatility and were able to extend AITC shelf life compared with free AITC
      (65% vs. 20% in 24 h, respectively). Cell viability and uptake of AITC-loaded
      nanoparticles were studied in vitro, showing that the protection and sustained
      release of AITC from polymeric NPs involved a larger toxicity of tumoral cells.
      These nanoparticles could be used as protective systems for enhancing a
      biological activity.

PMID- 28449616
TI  - Obesogenic environments: current evidence of the built and food environments.
AB  - AIMS: Obesity is one of the most significant global health and social problems,
      with rates rising dramatically over the past few decades. While the basic drivers
      of obesity are obvious (more energy consumed than expended), the causes are
      multifactorial and complex. A decade ago, it was suggested that exploring the
      ways in which the built environment influenced physical activity and dietary
      behaviours might provide fertile ground for investigation. This article overviews
      current evidence and, in particular, emergent themes that are of significance for
      the United Kingdom. METHODS: This article is based on literature extracted from
      keyword searching of electronic databases. A timeframe of 2006-2016 was used.
      RESULTS: In the past decade, the research base has grown significantly; while
      frustratingly some results are still inconclusive or contradictory, it might be
      argued enough evidence exists to act upon. Themes such as the importance of the
      journey to school for young people and the multiple environments in which people
      spend their time are examples of where real progress has been made in the
      evidence base. CONCLUSION: Progress towards real change in policy and practice
      may seem slow; however, the opportunities afforded for health and planning
      professionals to work together provide a step towards the whole systems
      approaches to tackle obesity that are desperately needed.

PMID- 28449618
TI  - Telerehabilitation after arthroscopic subacromial decompression is effective and
      not inferior to standard practice: Preliminary results.
AB  - Background Telerehabilitation promises to improve quality, increase patient
      access and reduce costs in health care. Physiotherapy with exercises is generally
      recommended to restore function after surgery in patients with chronic
      subacromial syndrome. Relatively few studies have investigated the feasibility of
      telerehabilitation interventions in musculoskeletal and orthopaedic disorders.
      The aim of this study was to evaluate the feasibility and effectiveness of a
      customizable telerehabilitation intervention and compare with traditional care.
      Methods This research includes 18 consecutive patients with subacromial
      impingement who underwent arthroscopic subacromial decompression in a controlled
      clinical prospective study. Patients were randomized to either a 12-week
      telerehabilitation programme or the usual face-to-face physical therapy for
      immediate postoperative rehabilitation. We have developed a telerehabilitation
      system to provide services to patients who have undergone shoulder arthroscopy.
      An independent blinded observer performed postoperative follow-up after 4, 8, and
      12 weeks. Results The preliminary efficacy of this telerehabilitation programme
      in terms of both physical and functional objective outcome measures was assessed
      on eight patients. Using the Constant-Murley score to evaluate functional
      outcome, patients in the telerehabilitation group were shown to have improved
      from a mean 43.50 +/- 3.21 points to a mean 68.50 +/- 0.86 points after 12 weeks.
      The physical and functional improvements in the telerehabilitation group were
      similar to those in the control group ( p = 0.213). There was a non-significant
      trend for greater improvements in the telerehabilitation group for most outcome
      measurements. Conclusion The results of this study provide evidence for the
      efficacy of telerehabilitation after shoulder arthroscopy in shoulder impingement
      syndrome. A telerehabilitation programme with range of motion, strengthening of
      the rotator cuff and scapula stabilizers exercises seems to be similar and not
      inferior to traditional face-to-face physiotherapy after subacromial arthroscopic
      decompression. Through this study, we are developing our preliminary dataset to
      evaluate the efficacy of telerehabilitation programmes following surgical
      procedures in musculoskeletal injuries and for comparison with more traditional
      interventions.

PMID- 28449619
TI  - The effectiveness of telehealth on self-management for older adults with a
      chronic condition: A comprehensive narrative review of the literature.
AB  - Introduction Given the rapid global growth of older adults with chronic
      condition(s), the present study explored the effects of telehealth technologies
      on self-management among older adults with chronic condition(s). Methods Clinical
      trial studies on telehealth self-management for older adults with chronic
      condition(s) published in peer reviewed journals were reviewed systematically. In
      addition, the potential biases were assessed for included studies. Results This
      review identified 31 articles regarding the effectiveness of telehealth
      technologies on self-management among older adults. Discussion According to the
      findings of the present study, telehealth technologies have shown effectiveness
      on improving self-care skills, improving self-monitoring behaviours and improving
      clinical outcomes among older adults with chronic condition(s) in different
      settings. Using telehealth technologies is an advisable intervention for
      promoting older patients' self-management. However, it is critical to consider
      racial diversity and culture-related health behaviour differences when using
      telehealth technologies.

PMID- 28449620
TI  - Patients are willing to use telehealth for the multidisciplinary management of
      chronic musculoskeletal conditions: A cross-sectional survey.
AB  - Introduction Access to specialised multidisciplinary healthcare services is
      difficult for many patients with chronic musculoskeletal conditions. A possible
      solution could be delivery of care via telehealth. This study aims to identify
      current barriers in accessing healthcare services, and to determine if telehealth
      is an acceptable mode of healthcare delivery, from the perspective of patients
      with chronic musculoskeletal conditions. Methods Surveys were distributed to
      current patients receiving care within the Neurosurgical and Orthopaedic
      Physiotherapy Screening Clinic and Multidisciplinary Service (N/OPSC & MDS) at
      six facilities throughout Queensland, Australia. The 48-item survey evaluated
      five key areas including demographics; current barriers to attendance;
      satisfaction with current management provided by the N/OPSC & MDS; technology
      access and literacy; and attitudes and preference towards telehealth. Results In
      total, 85 patients (71%) completed the survey. The majority of patients were
      satisfied overall with the N/OPSC & MDS, but almost one-quarter of the patients
      reported ceasing treatment due to difficulty accessing services. Over half of the
      respondents were willing to use telehealth if it reduced the costs (53%) and time
      (57%) associated with attending appointments. Patients in paid employment were
      more likely (65%) to use telehealth if it reduced work absenteeism. Overall, 78%
      of patients were identified as having appropriate technology access to enable
      home telehealth. Specifically, 43% of patients would prefer home telehealth over
      having to travel to attend their appointments. Discussion The majority of N/OPSC
      & MDS patients are willing to engage in telehealth for the management of their
      chronic musculoskeletal condition. These findings justify consideration of
      telehealth as an additional method of service delivery within the existing N/OPSC
      & MD service.

PMID- 28449621
TI  - Emerging role of Radium-223 in the growing therapeutic armamentarium of
      metastatic castration-resistant prostate cancer.
AB  - INTRODUCTION: During the last few years, the therapeutic armamentarium of
      castration resistant prostate cancer (mCRPC) has been enriched with the
      introduction of new effective therapies with proved survival benefit and quality
      of life gain, including cabazitaxel, abiraterone, enzalutamide, and Radium-223.
      Areas covered: Bone metastases represent a substantial cause of morbidity in
      mCRPC with a high rate of related skeletal events (SREs). In case of multifocal
      pain due to diffuse osteoblastic metastases, treatment with bone-targeting
      radiopharmaceutical agents can provide palliation from pain. Radium-223, a
      calcium-mimetic, is the first alpha-particle emitting radiopharmaceutical that
      prolonged overall survival, delayed symptomatic skeletal events and improved
      quality of life in mCRPC. Expert opinion: In this therapeutic scenario, no clear
      evidences support the best way to sequence these available agents and there is an
      urgent need for prospective studies to define it. 223Ra is a firmly established
      therapeutic option in CRPC with symptomatic bone metastases and no visceral/bulky
      nodal involvement, with an undeniable advantage over new hormonal agents, given
      its peculiar mechanism of action. Current ongoing randomized clinical trials will
      clarify the optimal use of this effective therapy in the therapeutic
      armamentarium of CRPC either alone or combined with other new approved agents and
      whether there is a role in patients with asymptomatic disease.

PMID- 28449622
TI  - Diabetes type 2 management: what are the differences between DPP-4 inhibitors and
      how do you choose?

PMID- 28449623
TI  - Why search for a sperm donor online? The experiences of women searching for and
      contacting sperm donors on the internet.
AB  - Whilst studies have examined the experiences of women who use clinic donors, to
      date there has been limited research investigating women's motivations and
      experiences of searching for a sperm donor online. A total of 429 women looking
      for a sperm donor on Pride Angel (a website that facilitates contact between
      donors and recipients) completed an online survey. Fifty-eight percent (249) saw
      advantages of obtaining donated sperm online with the most common advantage
      reported as being able to connect with and meet the donor (n = 50 (24%)). A third
      (n = 157 (37%)) of the participants gave disadvantages, the most common reported
      was encountering 'dishonest donors' (n = 63 (40%)). Most recipients (n = 181
      (61%)) wanted the donor to be 'just a donor' (i.e. to provide sperm and have no
      further contact). Whilst it was important for recipients to know the identity of
      the donor, some did not see this as important for the child and thus the level of
      information that parents have about the donor, and that which the child has, can
      differ. Finding a donor online blurs the distinction between categories of
      'anonymous', 'known' and 'identity release' donations. Whilst the survey had a
      large sample size, the representativeness of the sample is not known.

PMID- 28449624
TI  - An economic analysis of tolvaptan compared with fluid restriction among
      hospitalized patients with hyponatremia.
AB  - OBJECTIVE: The vasopressin-receptor antagonist tolvaptan is used for the
      treatment of hyponatremia (HN) in hospitalized patients with congestive heart
      failure (CHF) or syndrome of inappropriate antidiuretic hormone secretion
      (SIADH). The objective of this economic modeling study was to assess the
      potential cost and health outcomes associated with tolvaptan in comparison with
      fluid restriction (FR). METHODS: A decision-analytic model was developed to
      estimate potential cost and health outcomes associated with tolvaptan compared
      with FR among hospitalized CHF and SIADH patients with severe HN (serum sodium
      [SS] levels < 125 mEq/L). The model, which was populated with data from the
      published literature, assumes that response to treatment influences hospital
      length of stay, probability of an intensive care unit (ICU) admission, and
      probability of a 30-day all-cause hospital readmission. One-way and probabilistic
      sensitivity analyses (PSAs) assessed the influence of parameter uncertainty on
      model results. RESULTS: Model results suggest that, among hospitalized CHF
      patients with severe HN, the use of tolvaptan compared with FR may lead to
      reductions of 7.2% and 4.6% in ICU admissions and 30-day readmissions,
      respectively. Compared with FR, tolvaptan may result in total cost-savings of
      $156 per hospitalized CHF patient. Among hospitalized SIADH patients with severe
      HN, the model suggested reductions of 14.6% and 5.1% in ICU admissions and 30-day
      readmissions, respectively. Compared with FR, tolvaptan may result in total cost
      savings of $135 per hospitalized SIADH patient. PSAs found that the probabilities
      of net cost-savings from the use of tolvaptan compared with FR were 64% and 59%
      among patients with severe HN with CHF and SIADH, respectively. CONCLUSIONS:
      Decision-analytic modeling based on published data for hospitalized CHF and SIADH
      patients with severe HN, indicates that tolvaptan compared with FR has the
      potential to improve health outcomes and produce cost-savings that more than
      offset the cost of tolvaptan.

PMID- 28449625
TI  - Clinical Study of Orthogonal-View Phase-Matched Digital Tomosynthesis for Lung
      Tumor Localization.
AB  - BACKGROUND AND PURPOSE: Compared to cone-beam computed tomography, digital
      tomosynthesis imaging has the benefits of shorter scanning time, less imaging
      dose, and better mechanical clearance for tumor localization in radiation
      therapy. However, for lung tumors, the localization accuracy of the conventional
      digital tomosynthesis technique is affected by the lack of depth information and
      the existence of lung tumor motion. This study investigates the clinical
      feasibility of using an orthogonal-view phase-matched digital tomosynthesis
      technique to improve the accuracy of lung tumor localization. MATERIALS AND
      METHODS: The proposed orthogonal-view phase-matched digital tomosynthesis
      technique benefits from 2 major features: (1) it acquires orthogonal-view
      projections to improve the depth information in reconstructed digital
      tomosynthesis images and (2) it applies respiratory phase-matching to incorporate
      patient motion information into the synthesized reference digital tomosynthesis
      sets, which helps to improve the localization accuracy of moving lung tumors. A
      retrospective study enrolling 14 patients was performed to evaluate the accuracy
      of the orthogonal-view phase-matched digital tomosynthesis technique. Phantom
      studies were also performed using an anthropomorphic phantom to investigate the
      feasibility of using intratreatment aggregated kV and beams' eye view cine MV
      projections for orthogonal-view phase-matched digital tomosynthesis imaging. The
      localization accuracy of the orthogonal-view phase-matched digital tomosynthesis
      technique was compared to that of the single-view digital tomosynthesis
      techniques and the digital tomosynthesis techniques without phase-matching.
      RESULTS: The orthogonal-view phase-matched digital tomosynthesis technique
      outperforms the other digital tomosynthesis techniques in tumor localization
      accuracy for both the patient study and the phantom study. For the patient study,
      the orthogonal-view phase-matched digital tomosynthesis technique localizes the
      tumor to an average (+/- standard deviation) error of 1.8 (0.7) mm for a 30
      degrees  total scan angle. For the phantom study using aggregated kV-MV
      projections, the orthogonal-view phase-matched digital tomosynthesis localizes
      the tumor to an average error within 1 mm for varying magnitudes of scan angles.
      CONCLUSION: The pilot clinical study shows that the orthogonal-view phase-matched
      digital tomosynthesis technique enables fast and accurate localization of moving
      lung tumors.

PMID- 28449626
TI  - A Pilot Study Evaluating the Use of Dynamic Contrast-Enhanced Perfusion MRI to
      Predict Local Recurrence After Radiosurgery on Spinal Metastases.
AB  - PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging offers noninvasive
      characterization of the vascular microenvironment and hemodynamics. Stereotactic
      radiosurgery, or stereotactic body radiation therapy, engages a vascular
      component of the tumor response which may be detectable using dynamic contrast
      enhanced magnetic resonance imaging. The purpose of this study is to examine
      whether dynamic contrast-enhanced magnetic resonance imaging can be used to
      predict local tumor recurrence in patients with spinal bone metastases who
      undergo high-dose radiotherapy with stereotactic radiosurgery. MATERIALS AND
      METHODS: We conducted a study of 30 patients with spinal metastases who underwent
      dynamic contrast-enhanced magnetic resonance imaging before and after
      radiotherapy. Twenty patients received single-fraction stereotactic radiosurgery
      (24 Gy), while 10 received hypofractionated stereotactic radiosurgery (3-5
      fractions, 27-30 Gy total). Kaplan-Meier analysis was used to estimate the
      actuarial local recurrence rates. Two perfusion parameters (Ktrans: permeability
      and Vp: plasma volume) were measured for each metastasis. Percentage change in
      parameter values from pre- to posttreatment was calculated and compared. RESULTS:
      At 20-month median follow-up, 5 of the 30 patients had pathological evidence of
      local recurrence. One- and 3-year actuarial local recurrence rates were 24% and
      44% for the hypofractionated stereotactic radiosurgery cohort versus 5% and 16%
      for the single-fraction stereotactic radiosurgery cohort ( P = .20). The average
      change in Vp and Ktrans for patients without local recurrence versus those with
      local recurrence was -76% and -66% versus +28% and -14% ( P < .01 for both). With
      a cutoff point of -20%, Vp had a sensitivity, specificity, positive predictive
      value, and negative predictive value of 100%, 98%, 91%, and 100%, respectively,
      for the detection of local recurrence following high-dose radiotherapy. Using
      this definition, dynamic contrast-enhanced magnetic resonance imaging identified
      local recurrence up to 18 months (mean [standard deviation], 6.6 [6.8] months)
      earlier than standard magnetic resonance imaging. CONCLUSIONS: We demonstrated
      that changes in perfusion parameters, particularly Vp, after high-dose
      radiotherapy to spinal bone metastases were predictive of local tumor recurrence.
      These changes predicted local recurrence on average >6 months earlier than
      standard imaging did.

PMID- 28449627
TI  - Lornoxicam use to reduce the pain associated with propofol injection.
AB  - AIM: To investigate the efficacy of lornoxicam in the prevention of the pain
      associated with propofol injection. MATERIAL AND METHOD: Approval for this study
      was granted by the ethics committee of our hospital. Using a computer
      randomisation software, 120 patients undergoing elective surgery were assigned to
      four equal groups. In Group I (control group), immediately before anaesthesia
      induction, 10 ml of isotonic 0.9% NaCl solution (placebo) was administered
      intravenously (IV). In Groups II, III and IV, the same injection contained 2 mg,
      4 mg and 8 mg of lornoxicam respectively. A tourniquet was then applied to the
      forearm for two minutes. Pain evaluation was made using a verbal pain score.
      RESULTS: Differences in pain severity scores were statistically significant
      between Groups I and II, Groups I and III, Groups I and IV and between Groups II
      and III (p < 0.05). However, no significant difference was determined between
      Groups III and IV (p = 0.401). CONCLUSION: In all groups administered with
      lornoxicam, there was a significant reduction in the severity of pain associated
      with propofol injection, in comparison with the control group. Maximum effect is
      obtained with a dose of 4 mg.

PMID- 28449628
TI  - '. . . if you bring the kit home, you [can] get time and test together with your
      partner': Pregnant women and male partners' perceptions regarding female partner
      delivered HIV self-testing in Uganda - A qualitative study.
AB  - In 2015, the World Health Organization reported that more than 60 million people
      were tested for HIV in 122 low- and middle-income countries between 2010 and
      2014. Despite this level of progress, over 40% of people living with HIV remain
      unaware of their HIV status. This calls for innovative approaches to improve
      uptake of HIV testing services, including use of HIV self-test (HIVST) kits. We
      conducted a cross-sectional, qualitative study to assess pregnant women and their
      male partners' perceptions regarding female partner-delivered HIVST kits. This
      study was conducted at two health facilities in Central Uganda between November
      and December 2015. Data were collected on pregnant women's willingness to take
      HIVST kits to their male partners and other household members using eight focus
      group discussions and 30 in-depth interviews. Data were analyzed following a
      thematic framework approach. Overall, pregnant women were willing to take HIVST
      kits to their partners and other household members, with the exception of their
      cowives. Male partners were willing to use HIVST kits brought by their female
      partners. Our findings suggest that secondary distribution of HIVST kits through
      female partners is acceptable and has the potential to improve male partner and
      household-member HIV testing.

PMID- 28449629
TI  - The changing epidemiology of HIV in the criminal justice system.
AB  - Although the rate of HIV infection among US prison inmates is considerably higher
      than that of the general population, little is known about age-related changes in
      HIV-infected inmates over the last decade. This study of the nation's largest
      state prison system examined (1) whether the mean age of the HIV-infected inmate
      increased over the last decade, and (2) whether the prevalence of HIV and
      associated comorbidities varied according to age. The study population included
      all 230,103 inmates incarcerated in the Texas prison system for any duration
      during 2014. A separate analysis was conducted on all HIV-infected inmates
      incarcerated between 2004 and 2014. Information on medical conditions and
      demographic factors was obtained from an institution-wide electronic medical
      record system. From 2004 to 2014, the mean age of HIV-infected inmates in the
      prison system increased from 39.3 to 42.5 years, compared to an increase of 36.1
      37.9 for all Texas prison inmates. Multivariable logistic regression was used to
      assess the independent contributions of multiple demographic and clinical
      covariates in predicting the binary outcome, HIV infection. The model showed
      that, in 2014, HIV infection was elevated in inmates who were aged 40-49 years
      (OR = 3.1; 95% CI 2.7-3.3), aged 50-59 years (OR = 2.4; 95% CI 2.1-2.7), African
      American (OR = 3.0; 95% CI 2.8-3.3), and in those with several chronic diseases,
      including chronic obstructive pulmonary disease (OR = 1.7; 95% CI 1.5-1.9),
      hepatitis C (OR = 2.7; 95% CI 2.5-3.1), major depressive disorder (OR = 1.7; 95%
      CI 1.5-2.1), bipolar disorder (OR = 2.3; 95% CI 1.8-2.8), and schizophrenia (OR =
      1.5; 95% CI 1.3-1.8). Among HIV-infected inmates (n = 2960), the percentage with
      comorbid disease increased in a linear fashion according to age (p < .01).
      Correctional health systems must adapt to address the evolving epidemiology of
      HIV among inmate populations.

PMID- 28449630
TI  - Sevoflurane at 1.0 MAC together with remifentanil and propofol produces
      clinically acceptable intubation conditions at the vocal cords: A prospective
      randomized study.
AB  - : Objective The overall intubation conditions after tracheal intubation with
      remifentanil, propofol, and sevoflurane at 1.0 minimum alveolar concentration
      (MAC) are worse than with rocuronium at 0.45 mg/kg. Therefore, we compared the
      intubation conditions and laryngeal morbidity (vocal cord injuries, hoarseness,
      and sore throat) with sevoflurane at 1.2 and 1.4 MAC versus 1.0 MAC. Methods In
      this prospective clinical trial, 90 patients were randomized to 3 groups: the
      sevoflurane 1.0, 1.2, and 1.4 MAC groups. At 3 min, tracheal intubation was
      performed and the patients' intubation conditions were assessed. The vocal cords
      were examined for injury by videolaryngoscopy. Additionally, the incidence and
      severity of laryngeal morbidity were compared between women and men. Results
      Acceptable intubation conditions were seen in 72% of the patients without
      significant differences between the groups. Overall, vocal cord injuries (oedema)
      occurred in three (4%) patients. Women reported sore throat more often than men
      (51% vs. 21%, respectively). Conclusions Intubation conditions were not improved
      with higher sevoflurane concentrations. The incidence and severity of sore throat
      were greater in women than men. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT
      01896245.

PMID- 28449631
TI  - Effect and placental transfer of dexmedetomidine during caesarean section under
      epidural anaesthesia.
AB  - Objective To investigate the neonatal effect and placental transfer of
      dexmedetomidine during caesarean section under epidural anaesthesia. Methods
      Forty parturients with a single newborn who were scheduled for caesarean section
      were enrolled. Patients received 0.5 ug/kg dexmedetomidine 10 min after epidural
      anaesthesia, followed by 0.5 ug/kg/h until abdominal closure (Dex group) or
      infusion of normal saline (NS group). Systolic blood pressure (SBP), diastolic
      blood pressure (DBP), and heart rate (HR) were monitored before infusion (T0), 10
      min after infusion (T1), at delivery (T2), and at the end of the operation (T3).
      Umbilical vein and artery blood was collected. Apgar scores were evaluated at 1
      and 5 min after delivery. Results SBP, DBP, and HR in the Dex group were
      decreased at T3 compared with T0 (116 +/- 10.4 vs 111 +/- 9.2 mmHg, 74 +/- 6.7 vs
      66 +/- 7.9 mmHg, 91 +/- 12.1 vs 71 +/- 8.4 beats/min, respectively, P < 0.05). HR
      was lower at T1, T2, and T3 in the Dex group compared with the NS group ( P <
      0.05). There were no significant differences in blood gases and Apgar scores
      between the groups ( P > 0.05). Conclusion Dexmedetomidine during caesarean
      section under epidural anaesthesia is beneficial to parturients. The placental
      transfer rate is 0.68.

PMID- 28449632
TI  - Predicting the outcome of different protocols of in vitro fertilization with anti
      Muullerian hormone levels in patients with polycystic ovary syndrome.
AB  - Objective This study evaluated associations of basal serum and follicular fluid
      (FF) anti-Muullerian hormone (AMH) levels with in vitro fertilization (IVF)
      outcomes in polycystic ovary syndrome (PCOS) patients. Methods This prospective
      study included 179 consecutive women undergoing IVF, including 59 with PCOS and
      non-PCOS controls. Thirty PCOS cases had long gona-dotrophin-releasing hormone
      agonist (GnRH-a) and 29 had antagonist (GnRH-ant) protocols. Controls underwent
      conventional GnRH-a. Associations of basal serum and FF AMH levels with IVF
      outcomes were assessed. Results Median serum and FF AMH levels, antral follicle
      count (AFC), oestradiol human chorionic gonadotropin injection day (peak E2), and
      retrieved oocyte numbers were higher in PCOS patients than in controls (all P <
      0.01). Oocyte maturation and high-quality embryo rates were lower in PCOS
      patients than in controls (P < 0.01), but both groups had similar fertilization,
      implantation, clinical pregnancy, and newborn rates. Peak E2 was higher in GnRH
      ant than in GnRH-a protocols (16.5 nmol/L vs. 12.1 nmol/L, P < 0.05). AMH levels
      were correlated with AFC in PCOS patients ( P < 0.01). Peak E2 and FF AMH levels
      were independent predictors of oocyte number. Peak E2 predicted the fertilization
      rate. Conclusion Serum basal AMH levels are predictive of oocyte quantity, but
      not oocyte quality or IVF outcomes. Serum AMH, FF AMH, and outcomes are similar
      among protocols.

PMID- 28449633
TI  - Framing diabetes public health information during Ramadan - a newspaper content
      analysis.
AB  - Objective To evaluate health-related messages in printed media pertaining to
      diabetes care in Qatar during Ramadan. Methods Qatar national newspapers (Arabic
      and/or English) published 6 weeks prior to and 4 weeks during Ramadan 2012 were
      reviewed. Health-related content was identified and characterized according to
      four different categories including presence of messages pertaining to both
      diabetes and Ramadan. Articles describing diabetes and Ramadan combined were
      further evaluated according to specific features of prominence (surrogates for
      perceived reader importance). Newspapers were grouped by language, and volume and
      content of coverage were compared between groups. Results A total of 1 467
      newspaper issues published during the 2012 review period (781 in Arabic and 686
      in English) were analysed. Health-related articles appeared consistently
      throughout the study period, but few were specifically diabetes-related (66/1095
      [6%] Arabic articles versus 34/1250 [2.7%] English articles; P = 0.008). Only
      34/1095 (3.1%) Arabic and 23/1 250 (1.8%) English ( P = 0.05) articles pertaining
      specifically to diabetes management during Ramadan were published. Twenty/34
      (59%, Arabic) and 6/23 (26%, English) were published in high prominence
      positions. Conclusions Opportunity exists to augment the relatively low coverage
      of diabetes health-related messages in print media during Ramadan.

PMID- 28449634
TI  - Neuropsychiatric Associations With Gender, Illness Duration, Work Disability, and
      Motor Subtype in a U.S. Functional Neurological Disorders Clinic Population.
AB  - The assessment of functional neurological disorders (FND) requires an
      interdisciplinary approach. The authors retrospectively reviewed charts for 100
      outpatients with FND and used univariate and regression analyses to investigate
      neuropsychiatric associations with gender, illness duration, and work disability;
      secondary analyses evaluated for differences across motor FND subtypes. Men
      reported higher rates of cognitive complaints and functional weakness, whereas
      women endorsed increased past physical/sexual trauma. Number of self-reported
      medication allergies/sensitivities positively correlated with illness duration.
      Individuals with functional weakness compared with other motor FND subtypes
      exhibited lower rates of past psychiatric hospitalization and head trauma. This
      study supports the feasibility of integrating FND research.

PMID- 28449635
TI  - Seizure Control and Memory Impairment Are Related to Disrupted Brain Functional
      Integration in Temporal Lobe Epilepsy.
AB  - Brain functional integration can be disrupted in patients with temporal lobe
      epilepsy (TLE), but the clinical relevance of this disruption is not completely
      understood. The authors hypothesized that disrupted functional integration over
      brain regions remote from, as well as adjacent to, the seizure focus could be
      related to clinical severity in terms of seizure control and memory impairment.
      Using resting-state functional MRI data acquired from 48 TLE patients and 45
      healthy controls, the authors mapped functional brain networks and assessed
      changes in a network parameter of brain functional integration, efficiency, to
      examine the distribution of disrupted functional integration within and between
      brain regions. The authors assessed whether the extent of altered efficiency was
      influenced by seizure control status and whether the degree of altered efficiency
      was associated with the severity of memory impairment. Alterations in the
      efficiency were observed primarily near the subcortical region ipsilateral to the
      seizure focus in TLE patients. The extent of regional involvement was greater in
      patients with poor seizure control: it reached the frontal, temporal, occipital,
      and insular cortices in TLE patients with poor seizure control, whereas it was
      limited to the limbic and parietal cortices in TLE patients with good seizure
      control. Furthermore, TLE patients with poor seizure control experienced more
      severe memory impairment, and this was associated with lower efficiency in the
      brain regions with altered efficiency. These findings indicate that the
      distribution of disrupted brain functional integration is clinically relevant, as
      it is associated with seizure control status and comorbid memory impairment.

PMID- 28449636
TI  - Intrathecal Thyroid Autoantibody Synthesis in a Subgroup of Patients With
      Schizophreniform Syndromes.
AB  - Schizophreniform syndromes in combination with autoimmune thyroiditis and
      increased serum thyroid antibodies lead healthcare practitioners to consider a
      diagnosis of Hashimoto's encephalopathy. To detect specific biomarkers, the
      authors analyzed whether intrathecal antithyroid antibody synthesis occurred in a
      subgroup of schizophreniform patients. In doing so, the authors analyzed thyroid
      antibodies in paired cerebrospinal fluid and serum samples from 100
      schizophreniform patients. Increased antibody indices (AIs) for antithyroid
      peroxidase or antithyroglobulin autoantibodies in 13 schizophreniform patients
      were found. AIs were increased in 68% of the seropositive patients. These
      findings support the hypothesis that autoimmune processes may contribute to the
      pathophysiology in these patients.

PMID- 28449637
TI  - The effect of a dynamic chair on seated energy expenditure.
AB  - Dynamic sitting approaches have been advocated to increase seated energy
      expenditure with the view of lessening the sedentary nature of the task. This
      study compared energy expenditure (EE) and overall body discomfort on a novel
      dynamic chair with a standard office chair. Fifteen pain-free participants
      completed a DVD viewing task on both chairs in a randomised order. Energy
      expenditure and discomfort were collected simultaneously. Linear mixed models
      were used to analyse steady-state EE recorded on each of the chairs. Differences
      in discomfort were analysed using Wilkoxon Signed Rank Tests. Sitting on the
      novel dynamic chair significantly (p = 0.005) increased energy expenditure
      compared to a standard office chair. The discomfort experienced was mild overall,
      but was significantly greater on the dynamic chair (p = 0.004). Whilst the EE was
      seen to be significantly higher on the dynamic chair, the MET values are still
      below 1.5 METS. Thus, the use of a dynamic chair does not seem to be the most
      effective measure to prevent sedentary behaviour. Practitioner Summary: Sitting
      on a dynamic chair increased energy expenditure compared to sitting on a standard
      office chair among pain-free participants. Whilst the EE was seen to be
      significantly higher on the dynamic chair, the MET values are still below 1.5
      METS (low level EE).

PMID- 28449638
TI  - Recent advances in proteomics of cereals.
AB  - Cereals contribute a major part of human nutrition and are considered as an
      integral source of energy for human diets. With genomic databases already
      available in cereals such as rice, wheat, barley, and maize, the focus has now
      moved to proteome analysis. Proteomics studies involve the development of
      appropriate databases based on developing suitable separation and purification
      protocols, identification of protein functions, and can confirm their functional
      networks based on already available data from other sources. Tremendous progress
      has been made in the past decade in generating huge data-sets for covering
      interactions among proteins, protein composition of various organs and
      organelles, quantitative and qualitative analysis of proteins, and to
      characterize their modulation during plant development, biotic, and abiotic
      stresses. Proteomics platforms have been used to identify and improve our
      understanding of various metabolic pathways. This article gives a brief review of
      efforts made by different research groups on comparative descriptive and
      functional analysis of proteomics applications achieved in the cereal science so
      far.

PMID- 28449639
TI  - CloVR-Comparative: automated, cloud-enabled comparative microbial genome sequence
      analysis pipeline.
AB  - BACKGROUND: The benefit of increasing genomic sequence data to the scientific
      community depends on easy-to-use, scalable bioinformatics support. CloVR
      Comparative combines commonly used bioinformatics tools into an intuitive,
      automated, and cloud-enabled analysis pipeline for comparative microbial
      genomics. RESULTS: CloVR-Comparative runs on annotated complete or draft genome
      sequences that are uploaded by the user or selected via a taxonomic tree-based
      user interface and downloaded from NCBI. CloVR-Comparative runs reference-free
      multiple whole-genome alignments to determine unique, shared and core coding
      sequences (CDSs) and single nucleotide polymorphisms (SNPs). Output includes
      short summary reports and detailed text-based results files, graphical
      visualizations (phylogenetic trees, circular figures), and a database file linked
      to the Sybil comparative genome browser. Data up- and download, pipeline
      configuration and monitoring, and access to Sybil are managed through CloVR
      Comparative web interface. CloVR-Comparative and Sybil are distributed as part of
      the CloVR virtual appliance, which runs on local computers or the Amazon EC2
      cloud. Representative datasets (e.g. 40 draft and complete Escherichia coli
      genomes) are processed in <36 h on a local desktop or at a cost of <$20 on EC2.
      CONCLUSIONS: CloVR-Comparative allows anybody with Internet access to run
      comparative genomics projects, while eliminating the need for on-site
      computational resources and expertise.

PMID- 28449640
TI  - CD34 + tumours of the orbit including solitary fibrous tumours: a six-case
      series.
AB  - BACKGROUND: To report six cases of CD34+ fibroblastic mesenchymal tumours, which
      are uncommon neoplasms in the orbit. CASE PRESENTATION: Six patients presenting
      with proptosis and palpable mass who were later diagnosed with fibrous solitary
      tumours, fibrous histocytoma or haemangiopericytoma in the orbit were included.
      All patients received radiologic examinations and surgical excision for
      histopathology and immunohistochemistry examinations. Five patients had no
      recurrence after a minimum follow-up of 12 months. One patient (case 6)
      experienced recurrence twice, and had debulking surgeries each time. At present,
      the patient still has remnant tumour in the orbit, but no growth has been
      detected during the past two years. The tumour size will be closely monitored.
      CONCLUSIONS: Even though fibroblastic tumours are rarely found in the orbit, they
      can present as a palpable mass with proptosis. Complete surgical excision is
      important for long-term prognosis, and immunohistochemical study is helpful for
      confirming pathologic diagnosis.

PMID- 28449642
TI  - The effectiveness of double incision technique in uterus preserving surgery for
      placenta percreta.
AB  - BACKGROUND: Placenta percreta is a life-threatening condition that places
      patients at risk of massive bleeding. It necessitates very complicated surgery
      and can result in mortality. Caesarean hysterectomy is the accepted procedure
      worldwide; however, recent studies discussing conservative treatment with
      segmental resections have been published. Foetal extraction and segmental
      resection can be performed through the same incision (single uterine incision) or
      through two different incisions (double uterine incision). In this study, we
      aimed to evaluate the effectiveness and results of the double incision technique.
      METHODS: Twenty-two patients with a diagnosis of placenta percreta who underwent
      conservative surgery were included. Segmental resection was performed via single
      incision in ten patients and double incision in twelve patients. RESULTS: There
      was no difference between the patients who underwent segmental resection via
      single and double incision in terms of age, gravida, number of previous caesarean
      deliveries, gestational age at delivery, or rate of elective surgeries. The
      operation time, transfusion requirement, intensive care unit admission, total
      hospitalization and success of conservative surgery were comparable between the
      groups. CONCLUSIONS: Based on the outcomes of our study, double uterine incision
      allows for the safe extraction of the foetus during uterus-preserving surgery in
      patients with placenta percreta without worsening the results compared to single
      uterine incision. TRIAL REGISTRATION: NCT02702024 , Date of registration:
      February 26, 2016, retrospectively registered.

PMID- 28449643
TI  - QLiS-SF: Development of a short form of the quality of life in schizophrenia
      questionnaire.
AB  - BACKGROUND: There is a need for useful standardized Quality of Life (QoL)
      measures for people diagnosed with schizophrenia. Therefore, a short form of the
      self-administered Quality of Life in Schizophrenia (QLiS) scale was developed and
      validated. METHODS: Four steps were taken to develop the abridged version using
      samples from the Clinical Analysis of the Treatment of Schizophrenia (CATS)
      study. Firstly, a model with second order scales was developed using exploratory
      factor analysis (EFA). Secondly, it was tested in an independent sample using
      confirmatory factor analysis (CFA). Thirdly, this model served as the basis for
      selecting items for the short form. Distributional properties, content reviews,
      and factor loadings were taken into account in this step. Fourthly, the resulting
      short form was validated through confirmatory factor analysis (CFA). Composite
      reliability scores were calculated for the new subscales. RESULTS: Three second
      order scales were constructed: illness-related quality of life (QoL), social life
      and finances, and global subjective well-being. CFA of the new theoretical model
      resulted in a CFI of 0.67 and absolute fit indices of CMIN/df = 2.55, RMSEA =
      0.08, SRMR = 0.09. The selected 13 items showed good statistical properties and
      good fit of content to subscale. Fit of the underlying theoretical model with the
      reduced number of items was tested in an independent sample. Absolute and fit
      indices of the short form model were satisfactory (CFI = 0.95, CMIN/df = 2.23,
      RMSEA = 0.06, SRMR = 0.04). Composite reliability scores for three subscales were
      above 0.70. CONCLUSIONS: The short form of the QLIS (QLiS-SF) showed good model
      fit and reliability. It should only be considered for use if the application of
      the long version is not suitable.

PMID- 28449641
TI  - Cell-free hemoglobin mediated oxidative stress is associated with acute kidney
      injury and renal replacement therapy in severe falciparum malaria: an
      observational study.
AB  - BACKGROUND: Intravascular hemolysis is an intrinsic feature of severe malaria
      pathophysiology but the pathogenic role of cell-free hemoglobin-mediated
      oxidative stress in severe malaria associated acute kidney injury (AKI) is
      unknown. METHODS: As part of a prospective observational study, enrolment plasma
      cell-free hemoglobin (CFH), lipid peroxidation markers (F2-isoprostanes (F2
      IsoPs) and isofurans (IsoFs)), red cell deformability, and serum creatinine were
      quantified in Bangladeshi patients with severe falciparum malaria (n = 107),
      uncomplicated malaria (n = 80) and sepsis (n = 28). The relationships between
      these indices and kidney function and clinical outcomes were examined. RESULTS:
      AKI was diagnosed at enrolment in 58% (62/107) of consecutive patients with
      severe malaria, defined by an increase in creatinine >=1.5 times expected
      baseline. Severe malaria patients with AKI had significantly higher plasma cell
      free hemoglobin (geometric mean CFH: 8.8 MUM; 95% CI, 6.2-12.3 MUM), F2
      isoprostane (56.7 pg/ml; 95% CI, 45.3-71.0 pg/ml) and isofuran (109.2 pg/ml; 95%
      CI, 85.1-140.1 pg/ml) concentrations on enrolment compared to those without AKI
      (CFH: 5.1 MUM; 95% CI, 4.0-6.6 MUM; P = 0.018; F2-IsoPs: 27.8 pg/ml; 95% CI, 23.7
      32.7 pg/ml; P < 0.001; IsoFs: 41.7 pg/ml; 95% CI, 30.2-57.6 pg/ml; P < 0.001).
      Cell-free hemoglobin correlated with markers of hemolysis, parasite burden (P.
      falciparum histidine rich protein 2 (PfHRP2)), and F2-IsoPs. Plasma F2-IsoPs and
      IsoFs inversely correlated with pH, positively correlated with creatinine, PfHRP2
      and fractional excretion of sodium, and were higher in patients later requiring
      hemodialysis. Plasma F2-IsoP concentrations also inversely correlated with red
      cell deformability and were higher in fatal cases. Mixed effects modeling
      including an interaction term for CFH and time showed that F2-IsoPs, IsoFs,
      PfHRP2, CFH, and red cell rigidity were independently associated with increasing
      creatinine over 72 h. Multivariable logistic regression showed that admission F2
      IsoPs, IsoFs and red cell deformability were associated with the need for
      subsequent hemodialysis. CONCLUSIONS: Cell-free hemoglobin and lipid peroxidation
      are associated with acute kidney injury and disease severity in falciparum
      malaria, suggesting a pathophysiological role in renal tubular injury. Evaluation
      of adjunctive therapies targeting cell-free hemoglobin-mediated oxidative stress
      is warranted.

PMID- 28449644
TI  - Erratum to: The altered gut microbiota in adults with cystic fibrosis.

PMID- 28449645
TI  - 24-month clinical outcomes of a treat-and-extend regimen with ranibizumab for wet
      age-related macular degeneration in a real life setting.
AB  - BACKGROUND: To evaluate the clinical effectiveness and analyze the outcomes of a
      treat-and-extend (T&E) treatment regimen with ranibizumab for wet age-related
      macular degeneration (ARMD) in real life clinical settings over the first 2 years
      (24 months) of treatment. METHODS: Retrospective analysis of visual acuity,
      spectral domain optical coherence tomography (SD-OCT) parameters and treatment
      burden data of 56 eyes of 54 unselected treatment naive patients diagnosed with
      exudative ARMD. Monthly injections were offered until no signs of disease
      activity such as intra-retinal (IRF) or sub-retinal fluid (SRF) were evident on
      SD-OCT, followed by a gradual extension of the treatment interval by 2 weeks
      until a maximum of 12 weeks. RESULTS: The study met its main objective,
      demonstrating a mean best-corrected visual acuity gain of 8.3 letters (mean 68.8
      +/- 11) at month 12 and 5.2 letters (mean 65.7 +/- 12.3) at 24 months compared to
      baseline (mean 60.5 +/- 8.9). Anatomical improvement was also documented with a
      mean reduction of central retinal thickness by 139.7 MUm at 24 months (244.9 +/-
      48.3) compared to baseline (384.6 +/- 154.9). Forty-seven eyes (83.9% N = 56)
      gained vision or preserved baseline vision with 23 eyes (41.1%) gaining 10
      letters or more at month 12. Out of the 46 eyes that completed 24 months of
      treatment and monitoring, 27 (58.7% N = 46) kept a BCVA above baseline with 18 of
      those (39% N = 46) maintaining a 10-letter gain throughout the 24 months. Six
      eyes (13% N = 46) lost more than 10 letters by month 24. The mean number of
      injections was 12.1 +/- 2.8 over the 24-month period. Twenty-seven eyes (55.1% N
      = 56) achieved a treatment interval of 10 weeks or more at month 12, while the
      respective number at month 24 was 20 eyes (43.4% N = 46) in addition though to
      four more patients (8.7% N = 46) who were not receiving injections at month 24
      since they were placed on a Monitor & Extend regime. CONCLUSIONS: This is the
      first UK real-life study of a T&E treatment protocol with ranibizumab for
      exudative ARMD in a 24-month period and suggests that such a regimen is
      clinically effective and can achieve favourable outcomes with a significant
      reduction of the treatment burden compared to monthly PRN.

PMID- 28449646
TI  - When is the use of pacifiers justifiable in the baby-friendly hospital initiative
      context? A clinician's guide.
AB  - BACKGROUND: The use of pacifiers is an ancient practice, but often becomes a
      point of debate when parents and professionals aim to protect and promote
      breastfeeding as most appropriately for nurturing infants. We discuss the current
      literature available on pacifier use to enable critical decision-making regarding
      justifiable use of pacifiers, especially in the Baby-Friendly Hospital Initiative
      context, and we provide practical guidelines for clinicians. DISCUSSION: Suck
      swallow-breathe coordination is an important skill that every newborn must
      acquire for feeding success. In most cases the development and maintenance of the
      sucking reflex is not a problem, but sometimes the skill may be compromised due
      to factors such as mother-infant separation or medical conditions. In such
      situations the use of pacifiers can be considered therapeutic and even provide
      medical benefits to infants, including reducing the risk of sudden infant death
      syndrome. The argument opposing pacifier use, however, is based on potential
      risks such as nipple confusion and early cessation of breastfeeding. The Ten
      Steps to Successful Breastfeeding as embedded in the Baby-Friendly Hospital
      Initiative initially prohibited the use of pacifiers in a breastfeeding friendly
      environment to prevent potential associated risks. This article provides a
      summary of the evidence on the benefits of non-nutritive sucking, risks
      associated with pacifier use, an identification of the implications regarded as
      'justifiable' in the clinical use of pacifiers and a comprehensive discussion to
      support the recommendations for safe pacifier use in healthy, full-term, and ill
      and preterm infants. The use of pacifiers is justifiable in certain situations
      and will support breastfeeding rather than interfere with it. Justifiable
      conditions have been identified as: low-birth weight and premature infants;
      infants at risk for hypoglyceamia; infants in need of oral stimulation to
      develop, maintain and mature the sucking reflex in preterm infants; and the
      achievement of neurobehavioural organisation. Medical benefits associated with
      the use of pacifiers include providing comfort, contributing towards
      neurobehavioural organisation, and reducing the risk of sudden infant death
      syndrome. Guidelines are presented for assessing and guiding safe pacifier use,
      for specific design to ensure safety, and for cessation of use to ensure normal
      childhood development.

PMID- 28449647
TI  - PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish
      population.
AB  - BACKGROUND: Platelet Endothelial Aggregation Receptor 1 (PEAR1), a membrane
      protein highly expressed in platelets and endothelial cells, plays a role in
      platelet contact-induced activation, sustained platelet aggregation and
      endothelial function. Previous reports implicate PEAR1 rs12041331 as a variant
      influencing risk in patients with coronary heart disease. We investigated whether
      genetic variation in PEAR1 predicts cardiovascular outcome in a white population.
      METHODS: In 1938 participants enrolled in the Flemish Study on Environment, Genes
      and Health Outcomes (51.3% women; mean age 43.6 years), we genotyped 9 tagging
      SNPs in PEAR1, measured baseline cardiovascular risk factors, and recorded
      Cardiovascular disease incidence. For SNPs, we contrasted cardiovascular disease
      incidence of minor-allele heterozygotes and homozygotes (variant) vs. major
      allele homozygotes (reference) and for haplotypes carriers vs. non-carriers. In
      adjusted analyses, we accounted for family clusters and baseline covariables,
      including sex, age, body mass index, mean arterial pressure, the total-to-HDL
      cholesterol ratio, smoking and drinking, antihypertensive drug treatment, and
      history of cardiovascular disease and diabetes mellitus. RESULTS: Over a median
      follow-up of 15.3 years, 238 died and 181 experienced a major cardiovascular
      endpoint. The multivariable-adjusted hazard ratios of eight PEAR1 SNPs, including
      rs12566888, ranged from 0.87 to 1.07 (P >=0.35) and from 0.78 to 1.30 (P >=0.15),
      respectively. The hazard ratios of three haplotypes with frequency >=10% ranged
      from 0.93 to 1.11 (P >=0.49) for mortality and from 0.84 to 1.03 (P >=0.29) for a
      cardiovascular complications. These results were not influenced by intake of
      antiplatelet drugs, nonsteroidal anti-inflammatory drugs, or both (P-values for
      interaction >= 0.056). CONCLUSIONS: In a White population, we could not replicate
      previous reports from experimental studies or obtained in patients suggesting
      that PEAR1 might be a susceptibility gene for cardiovascular complications.

PMID- 28449648
TI  - Development and evaluation of training resources to prepare health professionals
      for counselling pregnant women about non-invasive prenatal testing for Down
      syndrome: a mixed methods study.
AB  - BACKGROUND: The availability of non-invasive prenatal testing (NIPT) for
      aneuploidies is expanding rapidly throughout the world. Training health
      professionals to offer NIPT in a way that supports informed choice is essential
      for implementation. The aim of this study was to develop and evaluate a training
      package for health professionals to support the introduction of NIPT into
      clinical practice. METHODS: Training on NIPT was offered to health professionals,
      primarily midwives, involved in Down syndrome screening and testing in eight
      hospitals located in England and Scotland as part of a research study evaluating
      the implementation of NIPT in the UK National Health Service. Training was
      evaluated using a mixed methods approach that included quantitative
      questionnaires at three time points and post-training qualitative interviews. The
      questionnaires measured confidence, self-perceived knowledge and actual knowledge
      about NIPT for Down syndrome. Interviews explored opinions about the training and
      experiences of offering NIPT. RESULTS: The training provided to the health
      professionals was found to positively impact on their confidence in discussing
      NIPT with women in their clinic, and both their perceived and actual knowledge
      and understanding of NIPT was improved. Knowledge remained weak in four areas;
      cell-free fetal DNA levels increase with gestation; turnaround time for NIPT
      results; cell-free fetal DNA is placental in origin; and NIPT false positive
      rate. CONCLUSIONS: Training materials, including a lesson plan, PowerPoint
      presentation and written factsheet on NIPT, have been developed and evaluated for
      use in educating midwives and supporting the introduction of NIPT. Implementation
      of training should include a greater focus on the areas where knowledge remained
      low. Some groups of midwives will need additional training or support to optimise
      their confidence in discussing NIPT with women.

PMID- 28449649
TI  - A case of recurrent depressive disorder presenting with Alice in Wonderland
      syndrome: psychopathology and pre- and post-treatment FDG-PET findings.
AB  - BACKGROUND: Alice in Wonderland syndrome (AIWS) is a rare neuropsychiatric
      syndrome that typically manifests in distortion of extrapersonal visual image,
      altered perception of one's body image, and a disturbed sense of the passage of
      distance and time. Several conditions have been reported to contribute to AIWS,
      although its biological basis is still unknown. Here, we present the first case
      demonstrating a clear concurrence of recurrent depressive disorder and AIWS. The
      clinical manifestations and pre- and post-treatment fluorodeoxyglucose positron
      emission tomographic (FDG-PET) images provide insights into the
      psychopathological and biological basis of AIWS. CASE PRESENTATION: We describe a
      63-year-old Japanese male who developed two distinct episodes of major depression
      concurrent with AIWS. In addition to typical AIWS perceptual symptoms, he
      complained of losing the ability to intuitively grasp the seriousness of news and
      the value of money, which implies disturbance of high-order cognition related to
      estimating magnitude and worth. Both depression and AIWS remitted after treatment
      in each episode. Pre-treatment FDG-PET images showed significant hypometabolism
      in the frontal cortex and hypermetabolism in the occipital and parietal cortex.
      Post-treatment images showed improvement of these abnormalities. CONCLUSIONS: The
      clinical co-occurrence of depressive episodes and presentation of AIWS can be
      interpreted to mean that they have certain functional disturbances in common. In
      view of incapacity, indifference, devitalization, altered perception of one's
      body image, and disturbed sense of time and space, the features of AIWS analogous
      to those of psychotic depression imply a common psychopathological basis. These
      high-order brain dysfunctions are possibly associated with the metabolic
      abnormalities in visual and parietotemporal association cortices that we observed
      on the pre- and post-treatment FDG-PET images in this case, while the
      hypometabolism in the frontal cortex is probably associated with depressive
      symptoms.

PMID- 28449651
TI  - Impacts of counseling on knowledge, attitude and practice of medication use
      during pregnancy.
AB  - BACKGROUND: Counseling has a significant role in improving knowledge, attitude
      and practice outcomes of pregnant women towards medication use. Proper counseling
      thus could be beneficial to prevent any medication related misadventure during
      pregnancy. The present study was aimed to assess the knowledge, attitude and
      practice (KAP) of pregnant women towards their medications, to provide counseling
      regarding their understanding of medication use during pregnancy and evaluate the
      impacts of such counseling. METHODS: Pre- post interventional (counseling) study
      was conducted at Manipal Teaching Hospital, Nepal among pregnant women who
      presented with complication and were prescribed at least one medication. A total
      of 275 pregnant women were included in the study. A structured questionnaire was
      used to assess the knowledge, attitude and practice of pregnant women before and
      after counseling. The impacts of counseling were then evaluated using suitable
      statistical methods. RESULTS: Of the total participants 229 completed the post
      counseling survey. Majority of the participants were in the age group 20-24
      (43.2%), primigravida (59.4%) and in third trimester (58.6%). Housewives
      comprised 61.1% of participants and majority had received a University degree
      (33.2%). The mean and median scores assessed before counseling showed that there
      was no significant difference in the KAP scores with respect to age, trimester
      and gravidity whereas KAP scores with respect to occupation and level of
      education were statistically significant. There was an increase in mean and
      median KAP scores after counseling and the impacts of counseling was found to be
      statistically significant (p = <0.001). CONCLUSION: Counseling had a positive
      impact on knowledge, attitude and practice of pregnant women towards medication
      and thus it could be considered a suitable method to encourage safe medication
      during pregnancy.

PMID- 28449650
TI  - Structure, Genetics and Worldwide Spread of New Delhi Metallo-beta-lactamase
      (NDM): a threat to public health.
AB  - BACKGROUND: The emergence of carbapenemase producing bacteria, especially New
      Delhi metallo-beta-lactamase (NDM-1) and its variants, worldwide, has raised
      amajor public health concern. NDM-1 hydrolyzes a wide range of beta-lactam
      antibiotics, including carbapenems, which are the last resort of antibiotics for
      the treatment of infections caused by resistant strain of bacteria. MAIN BODY: In
      this review, we have discussed bla NDM-1variants, its genetic analysis including
      type of specific mutation, origin of country and spread among several type of
      bacterial species. Wide members of enterobacteriaceae, most commonly Escherichia
      coli, Klebsiella pneumoniae, Enterobacter cloacae, and gram-negative non
      fermenters Pseudomonas spp. and Acinetobacter baumannii were found to carry these
      markers. Moreover, at least seventeen variants of bla NDM-type gene differing
      into one or two residues of amino acids at distinct positions have been reported
      so far among different species of bacteria from different countries. The genetic
      and structural studies of these variants are important to understand the
      mechanism of antibiotic hydrolysis as well as to design new molecules with
      inhibitory activity against antibiotics. CONCLUSION: This review provides a
      comprehensive view of structural differences among NDM-1 variants, which are a
      driving force behind their spread across the globe.

PMID- 28449652
TI  - Potential of extravasated platelet aggregation as a surrogate marker for overall
      survival in patients with advanced gastric cancer treated with preoperative
      docetaxel, cisplatin and S-1: a retrospective observational study.
AB  - BACKGROUND: The theory of extravasated platelet aggregation in cancer lesions was
      recently introduced. We investigated the association of platelet aggregation in
      gastric cancer stroma with clinicopathological features, chemotherapeutic
      response, pathological response, and survival. METHODS: The study comprised 78
      patients with advanced gastric cancer who had undergone gastrectomy with or
      without combination of docetaxel, cisplatin and S-1 (DCS) as preoperative
      chemotherapy between 2005 and 2014. The patients were divided into two groups:
      patients who had received preoperative DCS therapy forming the p-DCS group and
      patients who had not received preoperative DCS therapy forming the control group.
      The 39 patients in the control group had received gastrectomy and postoperative
      chemotherapy of S-1 alone. Platelet aggregation in biopsy specimens before
      preoperative DCS therapy in the p-DCS group and at the time of diagnosis in the
      control group were evaluated using CD42b immunohistochemical staining. RESULTS:
      Twenty-four patients in the p-DCS group and 19 in the control group were found to
      have platelet aggregation in their cancer stroma. Patients with histologically
      confirmed platelet aggregation had significantly higher rates of chemoresistance
      (58.3%) than those without platelet aggregation (20.0%) (P = 0.019). According to
      multivariate analysis, CD42b expression (odds ratio: 5.102, 95% confidence
      interval: 1.039-25.00, P = 0.045) was correlated with chemoresistance. CD42b
      expression and histological non-responder status were both significantly
      correlated with poor overall survival (OS) (P = 0.012, P = 0.016); however,
      RECIST was not correlated with OS. In the control group, CD42b expression was
      also significantly correlated with poor overall survival (OS) (P = 0.033). In the
      p-DCS group, according to multivariate analysis, male sex (hazard ratio: 0.281,
      95% confidence interval: 0.093-0.846, P = 0.024) was correlated with good
      prognosis and CD42b expression (hazard ratio: 4.406, 95% confidence interval:
      1.325-14.65, P = 0.016) with poor prognosis. CONCLUSIONS: This study suggests
      that platelets in gastric cancer stroma may create a favorable microenvironment
      for chemoresistance. CD42b immunohistochemical staining of biopsy specimens is a
      promising candidate for being a prognostic marker in patients with gastric
      cancer.

PMID- 28449653
TI  - A case report of parapneumonic pleural effusion caused by Streptococcus
      pneumoniae serotype 19A in a child immunized with 13-valent conjugate
      pneumococcal vaccine.
AB  - BACKGROUND: Simple parapneumonic effusion is a pleural effusion associated with
      lung infection (i.e., pneumonia). Streptococcus pneumoniae remains the most
      common pathogen causing parapneumonic effusions. In Morocco, the pneumococcal
      conjugate vaccine 13-valent (PCV13) was introduced in the national immunization
      program in October 2010 in 2 + 1 schedule for prevention of pneumococcal disease,
      and replaced by the PCV10 in July 2012 in the same schedule. We report a case of
      parapneumonic pleural effusions caused by S. pneumoniae serotype 19A in a child
      immunized with 3 doses of PCV13. CASE PRESENTATION: This is a 2.5 years old
      previously healthy Moroccan female, fully vaccinated by PCV13 and
      immunocompetent, admitted to a private medical clinic with a six months history
      of persistent asthma. On arrival (7 February 2015), she was febrile to 40.3 
      degrees C with a brutal flu syndrome, chills, dry cough and serous rhinitis, for
      which she received symptomatic treatment. A biological assessment was done that
      confirmed the clinical diagnosis of flu. Seven days after, she presented a
      progressive deterioration of its general condition and the onset of severe
      abdominal pain. She was hospitalized and a second biological assessment, computed
      tomography scans and chest radiography were done that confirmed a diagnosis of a
      pneumococcal parapneumonia with abscess of the left lower lobe with encysted
      empyema. Microbiological analysis of the pleural fluid showed a S. pneumoniae
      serotype 19A with susceptibility intermediate to penicillin. The patient was
      treated by antibiotics including amoxicillin, cefixime ceftriaxone and
      vancomycin. CONCLUSIONS: We reported a case of parapneumonic pleural effusions
      caused by a vaccine serotype pneumococcal 19A occurring in an immunocompetent
      child immunized with 3 doses of PCV13.

PMID- 28449654
TI  - Inter- and intra-species variation in genome-wide gene expression of Drosophila
      in response to parasitoid wasp attack.
AB  - BACKGROUND: Parasitoid resistance in Drosophila varies considerably, among and
      within species. An immune response, lamellocyte-mediated encapsulation, evolved
      in a subclade of Drosophila and was subsequently lost in at least one species
      within this subclade. While the mechanisms of resistance are fairly well
      documented in D. melanogaster, much less is known for closely related species.
      Here, we studied the inter- and intra-species variation in gene expression after
      parasitoid attack in Drosophila. We used RNA-seq after parasitization of four
      closely related Drosophila species of the melanogaster subgroup and replicated
      lines of D. melanogaster experimentally selected for increased resistance to gain
      insights into short- and long-term evolutionary changes. RESULTS: We found a core
      set of genes that are consistently up-regulated after parasitoid attack in the
      species and lines tested, regardless of their level of resistance. Another set of
      genes showed no up-regulation or expression in D. sechellia, the species unable
      to raise an immune response against parasitoids. This set consists largely of
      genes that are lineage-restricted to the melanogaster subgroup. Artificially
      selected lines did not show significant differences in gene expression with
      respect to non-selected lines in their responses to parasitoid attack, but
      several genes showed differential exon usage. CONCLUSIONS: We showed substantial
      similarities, but also notable differences, in the transcriptional responses to
      parasitoid attack among four closely related Drosophila species. In contrast,
      within D. melanogaster, the responses were remarkably similar. We confirmed that
      in the short-term, selection does not act on a pre-activation of the immune
      response. Instead it may target alternative mechanisms such as differential exon
      usage. In the long-term, we found support for the hypothesis that the ability to
      immunologically resist parasitoid attack is contingent on new genes that are
      restricted to the melanogaster subgroup.

PMID- 28449655
TI  - Early surgery with antibiotics treatment had better clinical outcomes than
      antibiotics treatment alone in patients with pyogenic spondylodiscitis: a
      retrospective cohort study.
AB  - BACKGROUND: Pyogenic spondylodiscitis is a form of spinal infection that can
      result in severe back pain and even death. However, information is lacking on the
      relative effectiveness of various therapies. A retrospective chart review was
      conducted to investigate whether early surgical treatment of pyogenic
      spondylodiscitis coupled with intravenous antibiotics results in better patient
      prognoses than intravenous antibiotics therapy alone. METHODS: All patients
      treated for pyogenic spondylodiscitis at a single medical center from July 2006
      to July 2011 were retrospectively reviewed. The inclusion criteria consisted of
      diagnosis of an early stage infection without neurological deficit, and patients
      without severe sepsis who were suitable candidates for early surgery as
      determined by a Pittsburgh bacteremia score < 4, and patients with delayed
      diagnosis and lost to outpatient follow-up were excluded. Clinical outcomes
      included patient demographic data, kyphosis angle, length of treatment, Oswestry
      Disability Index and visual analogue pain scale were analyzed. RESULTS: Of 90
      enrolled patients, Group 1 (n = 47) received only antibiotic therapy and Group 2
      (n = 43) received early surgery with post-surgery antibiotics for 2 to 4 weeks.
      Group 2 exhibited significantly better results than Group 1 for mean antibiotic
      administration period, mean hospitalization period, kyphotic angle correction. Of
      61 patients who participated in telephone follow-up after discharge, Group 2 (n =
      26) had significant lower mean ODI score, and mean back pain score than Group 1
      (n = 35). CONCLUSIONS: While infection control was similar for both groups,
      patients treated with early surgery and antibiotics were hospitalized for fewer
      days and required less antibiotics than those treated with antibiotics alone,
      also having better functional outcomes. In short, early surgical treatment of
      pyogenic spondylodiscitis typically achieves a better prognosis, shorter
      hospitalization period, and subsequent significant improvement in kyphotic
      deformity and quality of life.

PMID- 28449656
TI  - Improved tissue culture conditions for the emerging C4 model Panicum hallii.
AB  - BACKGROUND: Panicum hallii Vasey (Hall's panicgrass) is a compact, perennial C4
      grass in the family Poaceae, which has potential to enable bioenergy research for
      switchgrass (Panicum virgatum L.). Unlike P. hallii, switchgrass has a large
      genome, allopolyploidy, self-incompatibility, a long life cycle, and large
      stature-all suboptimal traits for rapid genetics research. Herein we improved
      tissue culture methodologies for two inbred P. hallii populations: FIL2 and HAL2,
      to enable further development of P. hallii as a model C4 plant. RESULTS: The
      optimal seed-derived callus induction medium was determined to be Murashige and
      Skoog (MS) medium supplemented with 40 mg L-1 L-cysteine, 300 mg L-1 L-proline,
      3% sucrose, 1 g L-1 casein hydrolysate, 3 mg L-1 2,4-dichlorophenoxyacetic acid
      (2,4-D), and 45 MUg L-1 6-benzylaminopurine (BAP), which resulted in callus
      induction of 51 +/- 29% for FIL2 and 81 +/- 19% for HAL2. The optimal
      inflorescence-derived callus induction was observed on MP medium (MS medium
      supplemented with 2 g L-1 L-proline, 3% maltose, 5 mg L-1 2,4-D, and 500 MUg L-1
      BAP), resulting in callus induction of 100 +/- 0.0% for FIL2 and 84 +/- 2.4% for
      HAL2. Shoot regeneration rates of 11.5 +/- 0.8 shoots/gram for FIL2 and 11.3 +/-
      0.6 shoots/gram for HAL2 were achieved using seed-induced callus, whereas shoot
      regeneration rates of 26.2 +/- 2.6 shoots/gram for FIL2 and 29.3 +/- 3.6
      shoots/gram for HAL2 were achieved from inflorescence-induced callus. Further,
      cell suspension cultures of P. hallii were established from seed-derived callus,
      providing faster generation of callus tissue compared with culture using
      solidified media (1.41-fold increase for FIL2 and 3.00-fold increase for HAL2).
      CONCLUSIONS: Aside from abbreviated tissue culture times from callus induction to
      plant regeneration for HAL2, we noted no apparent differences between FIL2 and
      HAL2 populations in tissue culture performance. For both populations, the cell
      suspension cultures outperformed tissue cultures on solidified media. Using the
      methods developed in this work, P. hallii callus was induced from seeds
      immediately after harvest in a shorter time and with higher frequencies than
      switchgrass. For clonal propagation, P. hallii callus was established from R1
      inflorescences, similar to switchgrass, which further strengthens the potential
      of this plant as a C4 model for genetic studies. The rapid cycling (seed-to-seed
      time) and ease of culture, further demonstrate the potential utility of P. hallii
      as a C4 model plant.

PMID- 28449657
TI  - Influence of subject discontinuation on long-term nonvertebral fracture rate in
      the denosumab FREEDOM Extension study.
AB  - BACKGROUND: Denosumab treatment for up to 8 years in the FREEDOM study and
      Extension was associated with low fracture incidence. It was not clear whether
      subjects who discontinued during the study conduct had a higher risk of fracture
      than those who remained enrolled, thereby underestimating the true fracture risk
      for the entire trial cohort. Thus, we explored the influence of early withdrawals
      on nonvertebral fracture incidence during the Extension study. METHODS: To
      understand the potential effect of depletion of susceptible subjects on fracture
      incidence, we first evaluated subject characteristics in patients who were
      enrolled in the Extension vs those who were not. We subsequently employed a
      Kaplan-Meier multiple imputation (KMMI) approach to consider subjects who
      discontinued as if they remained enrolled with a 0%, 20%, 50%, and 100% increase
      in fracture risk compared with participants remaining on study. RESULTS:
      Extension enrollees were generally similar to nonparticipants in median age (71.9
      and 73.1 years, respectively), mean total hip bone mineral density T-score (-1.9
      and -2.0, respectively), and probability of fracture risk by Fracture Risk
      Assessment Tool (FRAX(r)) at FREEDOM baseline (16.9% and 17.7% for major
      osteoporotic fracture and 6.7% and 7.4% for hip fracture, respectively). When we
      assumed a doubled fracture risk (100% increase) after discontinuation in KMMI
      analyses, nonvertebral fracture rate estimates were only marginally higher than
      the observed rates for both the crossover group (10.32% vs 9.16%, respectively)
      and the long-term group (7.63% vs 6.63%, respectively). CONCLUSION: The
      observation of continued denosumab efficacy over 8 years of treatment was robust
      and does not seem to be explained by depletion of susceptible subjects. TRIAL
      REGISTRATION: ClincalTrials.gov registration number NCT00523341 ; registered
      August 30, 2007.

PMID- 28449658
TI  - The effect of an online video intervention 'Movie Models' on specific parenting
      practices and parental self-efficacy related to children's physical activity,
      screen-time and healthy diet: a quasi experimental study.
AB  - BACKGROUND: In children, being sufficiently physically active, having low levels
      of screen-time and having a healthy diet are largely influenced by parenting
      practices. Children of parents applying positive parenting practices are at lower
      risk for overweight and obesity. Therefore, we investigated the effect of a
      health promoting online video intervention for parents ('Movie Models') on
      children's physical activity (PA), screen-time and healthy diet, and on specific
      parenting practices and parental self-efficacy related to these parenting
      practices. The online videos are delivered to parents of primary schoolchildren,
      and were based on real-life scenarios. METHODS: A two-armed, quasi experimental
      design was used. Parents of primary schoolchildren were recruited between
      November and December 2013 by spreading an appeal in social media, and by
      contacting primary schools. Participating parents were predominantly of high
      socio-economic status (SES) (83.1%), and only 6.8% of children were
      overweight/obese. Intervention group participants were invited to watch online
      videos for 4 weeks. Specific parenting practices, parental self-efficacy, PA,
      screen-time and healthy diet of the child were assessed at baseline (T0), at one
      (T1) and at four (T2) months post baseline. Repeated Measures (Multivariate)
      ANOVAs were used to examine intervention effects. The potential moderating effect
      of age and gender of the child and parental SES was also examined. RESULTS:
      Between T0 and T2, no significant intervention effects were found on children's
      PA, screen-time or healthy diet. Most significant intervention effects were found
      for more complex parenting practices (e.g., an increase in motivating the child
      to eat fruit). Subgroup analyses showed that the intervention had more effect on
      the actual parenting practices related to PA, screen-time and healthy diet in
      parents of older children (10-12 years old), whereas intervention effects on
      parental self-efficacy related to those behaviors were stronger in parents of
      younger children (6-9 years old). CONCLUSIONS: 'Movie Models' was effective in
      increasing some important parenting practices and parental self-efficacy related
      to PA, screen-time and healthy diet in children. Therefore, the current study is
      an important first step in promoting effective parenting-related factors, and
      possibly increasing children's healthy diet and PA, and decreasing screen-time.
      TRIAL REGISTRATION: NCT02278809 in ClinicalTrials.gov on October 28, 2014
      (retrospectively registered).

PMID- 28449659
TI  - Vitamin D and activated vitamin D in tuberculosis in equatorial Malaysia: a
      prospective clinical study.
AB  - BACKGROUND: Vitamin D deficiency (low plasma 25-hydroxyvitamin D [25D]
      concentration) is often reported in tuberculosis. Adjunctive vitamin D has been
      tested for its potential to improve treatment outcomes, but has proven largely
      ineffective. To better understand vitamin D in tuberculosis, we investigated
      determinants of 25D and its immunologically active form, 1,25-dihydroxyvitamin D
      (1,25D), their inter-relationship in tuberculosis, longitudinal changes and
      association with outcome. METHODS: In a prospective observational study of adults
      with smear-positive pulmonary tuberculosis in Sabah, Malaysia, we measured serial
      25D, 1,25D, vitamin D-binding protein (VDBP), albumin, calcium, parathyroid
      hormone, chest x-ray, week 8 sputum smear/culture and end-of-treatment outcome.
      Healthy control subjects were enrolled for comparison. RESULTS: 1,25D was
      elevated in 172 adults with tuberculosis (mean 229.0 pmol/L, 95% confidence
      interval: 215.4 - 242.6) compared with 95 controls (153.9, 138.4-169.4, p <
      0.001), directly proportional to radiological severity (p < 0.001), and fell
      rapidly within one week of treatment commencement. Tuberculosis patients with
      higher baseline 1,25D achieved significantly higher percentage weight gain over
      time, including when controlling for baseline weight, however persistently
      elevated 1,25D was associated with worse residual x-ray changes and lower end-of
      treatment BMI. 1,25D was inversely associated with PTH (p < 0.001), consistent
      with the extra-renal origin of the 1,25D. 25D did not differ between tuberculosis
      patients (mean 63.9 nmol/L, 95% CI: 60.6 - 67.3) and controls (61.3, 57.2- 65.3,
      p = 0.24), and was unassociated with outcomes. Among tuberculosis patients in
      multivariable analyses, sex, age and VDBP were associated with 25D, and age and
      albumin with 1,25D. 1,25-dihydroxyvitamin was not significantly asscociated with
      25D. Vitamin D deficiency <25 nmol/L was uncommon, occurring in only five TB
      patients; 1,25D was elevated in three of them. CONCLUSIONS: In an equatorial
      setting, high extra-renal production of 1,25D was seen in tuberculosis, including
      in individuals with 25D in the deficient range; however, severe 25D deficiency
      was uncommon. Baseline elevation of 1,25D, a marker of macrophage activation, was
      associated with better weight gain but persistent elevation of 1,25D was
      associated with worse radiological and BMI outcomes. 1,25D warrants testing in
      larger datasets including TB patients less responsive to treatment, such as multi
      drug resistant TB, to test its utility as a marker of tuberculosis severity and
      treatment response.

PMID- 28449660
TI  - Selective measurement of alpha smooth muscle actin: why beta-actin can not be
      used as a housekeeping gene when tissue fibrosis occurs.
AB  - BACKGROUND: Prevalence of fibroproliferative diseases, including chronic kidney
      disease is rapidly increasing and has become a major public health problem
      worldwide. Fibroproliferative diseases are characterized by increased expression
      of alpha smooth muscle actin (alpha-SMA) that belongs to the family of the six
      conserved actin isoforms showing high degree homology. The aim of the present
      study was to develop real-time PCRs that clearly discriminate alpha-SMA and beta
      actin from other actin isoforms. RESULTS: Real-time PCRs using self-designed
      mouse, human and rat specific alpha-SMA or beta-actin primer pairs resulted in
      the specific amplification of the artificial DNA templates corresponding to
      mouse, human or rat alpha-SMA or beta-actin, however beta-actin showed cross
      reaction with the housekeeping gamma-cyto-actin. We have shown that the use of
      improperly designed literary primer pairs significantly affects the results of
      PCRs measuring mRNA expression of alpha-SMA or beta-actin in the kidney of mice
      underwent UUO. CONCLUSION: We developed a set of carefully designed primer pairs
      and PCR conditions to selectively determine the expression of mouse, human or rat
      alpha-SMA and beta-actin isoforms. We demonstrated the importance of primer
      specificity in experiments where the results are normalized to the expression of
      beta-actin especially when fibrosis and thus increased expression of alpha-SMA is
      occur.

PMID- 28449661
TI  - Prognosis and treatment of non-metastatic primary and secondary breast
      angiosarcoma: a comparative study.
AB  - BACKGROUND: Breast angiosarcoma is a rare malignancy with limited publications
      confined to small retrospective case reviews and case reports. Knowledge of this
      disease is limited because information from previous studies is insufficient and
      inconsistent. METHODS: We obtained data from the Surveillance, Epidemiology, and
      End Results Program for non-metastatic primary and secondary breast angiosarcoma,
      and performed analysis to determine clinicopathological characteristics and
      estimate their associations with overall survival (OS). RESULTS: Median age was
      50-54 years in primary breast angiosarcoma and 70-74 years in secondary breast
      angiosarcoma, while median OS was 93 and 32 months, respectively. Age, tumor
      grade and tumor spread were associated with poor survival outcomes. Compared with
      primary breast angiosarcoma, patients with secondary breast angiosarcoma had a
      "nominal" increased death risk (HR = 1.89, 95% CI, 1.43-2.50, p < 0.001), which
      was driven by older age and more aggressive tumor phenotype at presentation.
      Mastectomy was associated with worse OS compared with breast conservative surgery
      (BCS) (adjHR = 2.47, 95% CI, 1.29-4.74) in primary angiosarcoma patients.
      Adjuvant radiation was associated with worse OS in secondary angiosarcoma
      patients (adjHR =1.77, 95% CI, 1.01-3.12). CONCLUSIONS: There is a "nominal"
      increased death risk in secondary breast angiosarcoma due to advanced
      clinicopathological features. Both BCS and mastectomy are feasible in primary and
      secondary angiosarcoma if R0 can be achieved. Routine radiation in unselected
      breast angiosarcoma should be cautious because there is no survival benefit in
      primary AS and appeared to be associated with a worse OS in secondary AS.

PMID- 28449662
TI  - An integrated RNAseq-1H NMR metabolomics approach to understand soybean primary
      metabolism regulation in response to Rhizoctonia foliar blight disease.
AB  - BACKGROUND: Rhizoctonia solani AG1-IA is a devastating phytopathogen causing
      Rhizoctonia foliar blight (RFB) of soybean worldwide with yield losses reaching
      60%. Plant defense mechanisms are complex and information from different
      metabolic pathways is required to thoroughly understand plant defense regulation
      and function. Combining information from different "omics" levels such as
      transcriptomics, metabolomics, and proteomics is required to gain insights into
      plant metabolism and its regulation. As such, we studied fluctuations in soybean
      metabolism in response to R. solani infection at early and late disease stages
      using an integrated transcriptomics-metabolomics approach, focusing on the
      regulation of soybean primary metabolism and oxidative stress tolerance. RESULTS:
      Transcriptomics (RNAseq) and metabolomics (1H NMR) data were analyzed
      individually and by integration using bidirectional orthogonal projections to
      latent structures (O2PLS) to reveal possible links between the metabolome and
      transcriptome during early and late infection stages. O2PLS analysis detected 516
      significant transcripts, double that reported in the univariate analysis, and
      more significant metabolites than detected in partial least squares discriminant
      analysis. Strong separation of treatments based on integration of the metabolomes
      and transcriptomes of the analyzed soybean leaves was revealed, similar trends as
      those seen in analyses done on individual datasets, validating the integration
      method being applied. Strong fluctuations of soybean primary metabolism occurred
      in glycolysis, the TCA cycle, photosynthesis and photosynthates in response to R.
      solani infection. Data were validated using quantitative real-time PCR on a set
      of specific markers as well as randomly selected genes. Significant increases in
      transcript and metabolite levels involved in redox reactions and ROS signaling,
      such as peroxidases, thiamine, tocopherol, proline, L-alanine and GABA were also
      recorded. Levels of ethanol increased 24 h post-infection in soybean leaves, and
      alcohol dehydrogenase (ADH) loss-of-function mutants of Arabidopsis thaliana had
      higher necrosis than wild type plants. CONCLUSIONS: As a proof-of-concept, this
      study offers novel insights into the biological correlations and identification
      of candidate genes and metabolites that can be used in soybean breeding for
      resistance to R. solani AG1-IA infection. Additionally, these findings imply that
      alcohol and its associated gene product ADH may have important roles in plant
      resistance to R. solani AG1-IA causing foliar blight.

PMID- 28449663
TI  - MiR-23b controls ALDH1A1 expression in cervical cancer stem cells.
AB  - BACKGROUND: Cancer stem cells has been widely investigated due to its essential
      role in cancer progression and drug resistance. Here, we try to find a new
      therapeutic target for cervical cancer stem cells. METHODS: We detected ALDH1A1
      associated miRNAs expression in our isolated tumorspheres and their corresponding
      parental cells. Sphere formation assay was also used to determine stemness after
      cells were manipulated with miR-23b plasmid or miR-23b inhibitor. RESULTS: We
      found that miR-23b was under-expressed in cervical cancer stem cells to maintain
      high levels of ALDH1A1. Introduction of miR-23b into cervical cancer cells could
      alter stemness and cisplatin sensitivity. CONCLUSIONS: miR-23b plays key role in
      maintaining stemness of cervical cancer stem cells and can be developed as
      therapeutic target to better fight against cervical cancer.

PMID- 28449664
TI  - Distinct immunophenotypes and prognostic factors in renal cell carcinoma with
      sarcomatoid differentiation: a systematic study of 19 immunohistochemical markers
      in 42 cases.
AB  - BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid differentiation is a
      relatively rare tumor containing both carcinoma and sarcomatoid components.
      However, there has not been a systemic study on immunophenotypes of renal cell
      carcinoma with sarcomatoid differentiation, especially using some renal specific
      immunohistochemical markers. In this study, we aimed to comprehensively
      investigate the distinct immunophenotypes of RCC with sarcomatoid differentiation
      to analyze the pathogenesis of sarcomatoid differentiation and identify new
      prognostic factors in RCC with sarcomatoid differentiation. METHODS: A total of
      42 cases of RCCs with sarcomatoid differentiation were enrolled into the study.
      Immunohistochemistry study was performed on tissue microarrays to evaluate the
      expressions of 19 immunohistochemical markers including a series of epithelial,
      mesenchymal markers and RCC specific markers. Kaplan-Meier method was applied to
      assess the prognostic values of CD10, CAIX, p53 and Bcl-2. RESULTS:
      Histologically, 42 cases of RCCs with sarcomatoid differentiation presented with
      different proportions of carcinoma and sarcomatoid components. The cohort
      contained 35 cases of clear cell renal cell carcinoma (CCRCC) and 7 cases of
      chromophobe renal cell carcinoma (ChRCC) based on the carcinoma components.
      Immunohistochemically, all cases were positive for vimentin, and 80% of cases
      showed immunostaining for at least one epithelial marker, such as CK, EMA, CK7
      and CK18. Notably, the expression rates of CAIX, CD10 and PAX8 in sarcomatoid
      cells were 76%, 76% and 64%, respectively. The carcinoma component of the tumors
      showed differentient labeling for CAIX, CD10, vimentin, CK7 and CD117 in CCRCC vs
      ChRCC, but the sarcomatoid component lost the specificity for these markers ( p <
      0.05). Patients with positive expressions of CAIX, p53 and Bcl-2 had a poor
      prognosis. CONCLUSIONS: The sarcomatoid cells in RCC with sarcomatoid
      differentiation express both epithelial and mesenchymal markers, supporting their
      epithelial origin. PAX8, CAIX and CD10 could be used as the reliable and useful
      markers to determine the renal origin of sarcomatoid cells such as in fine needle
      aspiration cases and metastatic RCC with sarcomatoid differentiation. CAIX, p53
      and Bcl-2 might play important roles in the transformation from renal cell
      carcinoma to high malignant sarcomatoid differentiation, and these three
      immunohistochemical markers are adverse prognostic factors for the survival of
      patients with RCC with sarcomatoid differentiation.

PMID- 28449665
TI  - Lymphoepithelioma-like, a variant of urothelial carcinoma of the urinary bladder:
      a case report and systematic review for optimal treatment modality for disease
      free survival.
AB  - BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare high-grade
      carcinoma that resembles nasopharyngeal lymphoepithelioma and can occur
      throughout the body. First reported in 1991, bladder LELC has an incidence of
      about 1% of all bladder carcinomas. Due to its rare occurrence, prognoses and
      ideal treatment guidelines have not been clearly defined. METHODS: A PubMed
      search was performed using two terms, "lymphoepithelioma-like carcinoma" and
      "bladder." Review articles, articles in foreign languages, expression studies,
      and studies not performed in the bladder were excluded. We report a case of LELC
      of the bladder including treatment and outcome and performed a systematic review
      of all 36 available English literatures from 1991 to 2016 including the present
      case to identify factors affecting disease-free survival. RESULTS: One hundred
      forty cases of bladder LELC were analyzed. The mean age of the patients was 70.1
      years ranging from 43 to 90 years with 72% males and 28% females. Pure LELC
      occurs most often at 46% followed by mixed LELC 28% and predominant LELC 26%. EBV
      testing was negative in all cases tested. Mean follow-up length for all cases was
      33.8 months with no evidence of disease in 62.2%, while 11.1% died of disease,
      10.4% alive with metastasis, and 8.2% died without disease. 5.0% of cases had
      recurrence at an average of 31.3 months. Prognosis is significantly favorable for
      patients presenting with pure or predominant forms of LELC compared to mixed type
      (p < 0.0001). The treatment significantly associated with the highest disease
      mortality and lowest disease-free survival was TURBT alone when compared to any
      multi-modality treatment (p < 0.01). CONCLUSION: We conclude that the best
      treatment modality associated with the highest disease-free survival is multi
      modal treatment including radical cystectomy.

PMID- 28449666
TI  - Nicotine, aerosol particles, carbonyls and volatile organic compounds in tobacco-
      and menthol-flavored e-cigarettes.
AB  - BACKGROUND: We aimed to assess the content of electronic cigarette (EC) emissions
      for five groups of potentially toxic compounds that are known to be present in
      tobacco smoke: nicotine, particles, carbonyls, volatile organic compounds (VOCs),
      and trace elements by flavor and puffing time. METHODS: We used ECs containing a
      common nicotine strength (1.8%) and the most popular flavors, tobacco and
      menthol. An automatic multiple smoking machine was used to generate EC aerosols
      under controlled conditions. Using a dilution chamber, we targeted nicotine
      concentrations similar to that of exposure in a general indoor environment. The
      selected toxic compounds were extracted from EC aerosols into a solid or liquid
      phase and analyzed with chromatographic and spectroscopic methods. RESULTS: We
      found that EC aerosols contained toxic compounds including nicotine, fine and
      nanoparticles, carbonyls, and some toxic VOCs such as benzene and toluene. Higher
      mass and number concentrations of aerosol particles were generated from tobacco
      flavored ECs than from menthol-flavored ECs. CONCLUSION: We found that diluted
      machine-generated EC aerosols contain some pollutants. These findings are limited
      by the small number of ECs tested and the conditions of testing. More
      comprehensive research on EC exposure extending to more brands and flavor
      compounds is warranted.

PMID- 28449668
TI  - Erratum to: In Memorian Thomas W. Hesterberg, PhD MBA (1950-2016).

PMID- 28449667
TI  - Depression, psychological distress and Internet use among community-based
      Australian adolescents: a cross-sectional study.
AB  - BACKGROUND: There has been rapid increase in time spent using Internet as a
      platform for entertainment, socialising and information sourcing. This study
      aimed to evaluate the relationship between duration of time spent using Internet
      for leisure, depressive symptoms, and psychological distress among Australian
      adolescents. METHODS: Depressive symptoms were indicated by the youth self-report
      module from the Diagnostic and Statistical Manual of Mental Disorders Version IV
      criteria, and psychological distress was measured by Kessler Psychological
      Distress scale. Internet use was self-reported based on use on an average
      weekday, and an average weekend day. Multivariate logistic regression models were
      used to examine the relationship between Internet use and mental health outcomes.
      Models were adjusted for potential confounders: age; relative level of socio
      economic disadvantage, and body mass index. RESULTS: Adolescents were aged 11-17
      years (M = 14.5 years, SD = 2.04 years). Greatest time spent using internet (>=7
      h a day) was significantly associated with experiencing depressive symptoms among
      females (OR = 2.09, 95% CI = 1.16, 3.76, p < 0.05), and high/very high levels of
      psychological distress for male (OR = 2.23, 95% CI = 1.36, 3.65, p < 0.01) and
      female (OR = 2.38, 95% CI = 1.55, 3.67, p < 0.01) adolescents. CONCLUSIONS: With
      current initiatives to improve health behaviours among adolescents to improve
      physical health outcomes such as overweight or obesity, it is imperative that the
      reciprocal relationship with mental health is known and included in such public
      health developments. Internet use may interact with mental health and therefore
      could be a modifiable risk factor to reach and improve mental health outcomes for
      this age group. Caution is advised in interpretation of findings, with some
      inconsistencies emerging from this evidence.

PMID- 28449669
TI  - A single trophectoderm biopsy at blastocyst stage is mathematically unable to
      determine embryo ploidy accurately enough for clinical use.
AB  - BACKGROUND: It has become increasingly apparent that the trophectoderm (TE) at
      blastocyst stage is much more mosaic than has been appreciated. Whether
      preimplantation genetic screening (PGS), utilizing a single TE biopsy (TEB), can
      reliably determine embryo ploidy has, therefore, increasingly been questioned in
      parallel. METHODS: We for that reason here established 2 mathematical models to
      assess probabilities of false-negative and false-positive results of an on
      average 6-cell biopsy from an approximately 300-cell TE. This study was a
      collaborative effort between investigators at The Center for Human Reproduction
      in New York City and the Center for Studies in Physics and Biology and the
      Brivanlou Laboratory of Stem Cell Biology and Molecular Embryology, the latter
      two both at Rockefeller University in New York City. RESULTS: Both models
      revealed that even under best case scenario, assuming even distribution of
      mosaicism in TE (since mosaicism is usually clonal, a highly unlikely scenario),
      a biopsy of at least 27 TE cells would be required to reach minimal diagnostic
      predictability from a single TEB. CONCLUSIONS: As currently performed, a single
      TEB is, therefore, mathematically incapable of reliably determining whether an
      embryo can be transferred or should be discarded. Since a single TEB, as
      currently performed, apparently is not representative of the complete TE, this
      study, thus, raises additional concern about the clinical utilization of PGS.

PMID- 28449670
TI  - Ethics of health research with prisoners in Canada.
AB  - BACKGROUND: Despite the growing recognition for the need to improve the health of
      prisoners in Canada and the need for health research, there has been little
      discussion of the ethical issues with regards to health research with prisoners
      in Canada. The purpose of this paper is to encourage a national conversation
      about what it means to conduct ethically sound health research with prisoners
      given the current realities of the Canadian system. Lessons from the Canadian
      system could presumably apply in other jurisdictions. MAIN TEXT: Any discussion
      regarding research ethics with Canadian prisoners must begin by first taking into
      account the disproportionate number of Indigenous prisoners (e.g., 22-25% of
      prisoners are Indigenous, while representing approximately 3% of the general
      Canadian population) and the high proportion of prisoners suffering from mental
      illnesses (e.g., 45% of males and 69% of female inmates required mental health
      interventions while in custody). The main ethical challenges that researchers
      must navigate are (a) the power imbalances between them, the correctional
      services staff, and the prisoners, and the effects this has on obtaining
      voluntary consent to research; and (b), the various challenges associated to
      protecting the privacy and confidentiality of study participants who are
      prisoners. In order to solve these challenges, a first step would be to develop
      clear and transparent processes for ethical health research, which ought to be
      informed by multiple stakeholders, including prisoners, the correctional services
      staff, and researchers themselves. CONCLUSION: Stakeholder and community
      engagement ought to occur in Canada with regards to ethical health research with
      prisoners that should also include consultation with various parties, including
      prisoners, correctional services staff, and researchers. It is important that
      national and provincial research ethics organizations examine the sufficiency of
      existing research ethics guidance and, where there are gaps, to develop
      guidelines and help craft policy.

PMID- 28449671
TI  - Effects of an educational intervention on oral hygiene and self-care among people
      with mental illness in Japan: a longitudinal study.
AB  - BACKGROUND: The oral hygiene of patients with a mental illness is an important
      concern in psychiatric care, and it is necessary to increase the level of self
      care among these patients. In this study, we administered an oral care
      questionnaire to people with mental illness in Japan and compared their answers
      before (baseline) and at 1 week and 1, 3 and 6 months after they participated in
      an educational program. METHODS: The questionnaire was distributed to 390
      patients. It included questions about age, education, income, between-meal
      snacks, number of teeth, frequency of tooth brushing, and other items. The
      educational program was developed for the purposes of improving self-care.
      RESULTS: Before the program, the proportion of male patients who had had a mental
      illness for >= 10 years was significantly higher among those patients who did not
      brush their teeth before bed. In addition, such patients did not have primary
      care dentists, and a significantly higher proportion of male patients, compared
      with female patients, did not undergo routine dental checkups more than once per
      year. The educational program resulted in an improvement in the use of fluoride
      toothpaste from baseline to 6 months after the intervention (p = 0.001). The
      daily use of interdental brushes or floss was significantly different 6 months
      after the intervention. CONCLUSIONS: Male and long-term inpatients need oral
      hygiene instructions. Our educational program showed the effects of using oral
      hygiene tools. Future studies should include a control group to measure the
      impact of the educational program.

PMID- 28449672
TI  - Compressed sensing MRI via fast linearized preconditioned alternating direction
      method of multipliers.
AB  - BACKGROUND: The challenge of reconstructing a sparse medical magnetic resonance
      image based on compressed sensing from undersampled k-space data has been
      investigated within recent years. As total variation (TV) performs well in
      preserving edge, one type of approach considers TV-regularization as a sparse
      structure to solve a convex optimization problem. Nevertheless, this convex
      optimization problem is both nonlinear and nonsmooth, and thus difficult to
      handle, especially for a large-scale problem. Therefore, it is essential to
      develop efficient algorithms to solve a very broad class of TV-regularized
      problems. METHODS: In this paper, we propose an efficient algorithm referred to
      as the fast linearized preconditioned alternating direction method of multipliers
      (FLPADMM), to solve an augmented TV-regularized model that adds a quadratic term
      to enforce image smoothness. Because of the separable structure of this model,
      FLPADMM decomposes the convex problem into two subproblems. Each subproblem can
      be alternatively minimized by augmented Lagrangian function. Furthermore, a
      linearized strategy and multistep weighted scheme can be easily combined for more
      effective image recovery. RESULTS: The method of the present study showed
      improved accuracy and efficiency, in comparison to other methods. Furthermore,
      the experiments conducted on in vivo data showed that our algorithm achieved a
      higher signal-to-noise ratio (SNR), lower relative error (Rel.Err), and better
      structural similarity (SSIM) index in comparison to other state-of-the-art
      algorithms. CONCLUSIONS: Extensive experiments demonstrate that the proposed
      algorithm exhibits superior performance in accuracy and efficiency than
      conventional compressed sensing MRI algorithms.

PMID- 28449673
TI  - The association between social support and physical activity in older adults: a
      systematic review.
AB  - BACKGROUND: The promotion of active and healthy ageing is becoming increasingly
      important as the population ages. Physical activity (PA) significantly reduces
      all-cause mortality and contributes to the prevention of many chronic illnesses.
      However, the proportion of people globally who are active enough to gain these
      health benefits is low and decreases with age. Social support (SS) is a social
      determinant of health that may improve PA in older adults, but the association
      has not been systematically reviewed. This review had three aims: 1)
      Systematically review and summarise studies examining the association between SS,
      or loneliness, and PA in older adults; 2) clarify if specific types of SS are
      positively associated with PA; and 3) investigate whether the association between
      SS and PA differs between PA domains. METHODS: Quantitative studies examining a
      relationship between SS, or loneliness, and PA levels in healthy, older adults
      over 60 were identified using MEDLINE, PSYCInfo, SportDiscus, CINAHL and PubMed,
      and through reference lists of included studies. Quality of these studies was
      rated. RESULTS: This review included 27 papers, of which 22 were cross sectional
      studies, three were prospective/longitudinal and two were intervention studies.
      Overall, the study quality was moderate. Four articles examined the relation of
      PA with general SS, 17 with SS specific to PA (SSPA), and six with loneliness.
      The results suggest that there is a positive association between SSPA and PA
      levels in older adults, especially when it comes from family members. No clear
      associations were identified between general SS, SSPA from friends, or loneliness
      and PA levels. When measured separately, leisure time PA (LTPA) was associated
      with SS in a greater percentage of studies than when a number of PA domains were
      measured together. CONCLUSIONS: The evidence surrounding the relationship between
      SS, or loneliness, and PA in older adults suggests that people with greater SS
      for PA are more likely to do LTPA, especially when the SS comes from family
      members. However, high variability in measurement methods used to assess both SS
      and PA in included studies made it difficult to compare studies.

PMID- 28449674
TI  - Nutritional status and quality of life of cancer patients needing exclusive
      chemotherapy: a longitudinal study.
AB  - BACKGROUND: The aims of this study were to report nutritional status in a large
      panel of patients with cancer requiring exclusive chemotherapy and to study the
      influence of nutritional status on their quality of life (QoL). METHODS: This
      work was a longitudinal cohort study performed at a French university teaching
      hospital. Eligible patients were individuals with a cancer needing treatment
      based on exclusive chemotherapy. Three work-ups were performed: i) before the
      administration of the first course of chemotherapy: T1, ii) before the
      administration of the second (for patients with 3 planned courses) or third
      (patients with 6 planned courses) course: T2, and iii) before the administration
      of the last planned course: T3. The following data were collected: general health
      (performance status) and nutritional status (weight, anorexia grading,
      albuminemia, pre-albuminemia, and C-reactive protein) and QoL. RESULTS: The
      nutritional status of patients with cancer was preserved. Functional impairment,
      the presence of anorexia, the palliative nature of the chemotherapy, and an
      elevated C-reactive protein dosage were independent predictive factors of a lower
      QoL among patients assessed at the end of chemotherapy. CONCLUSIONS: Although
      larger studies should corroborate these findings, clinicians may include this
      information in the management of patients with cancer requiring exclusive
      chemotherapy to identify the most vulnerable patients. TRIAL REGISTRATION:
      Current controlled trials NCT01687335 (registration date: October 6, 2011).

PMID- 28449675
TI  - A systematic approach for studying the signs and symptoms of fever in adult
      patients: the fever assessment tool (FAST).
AB  - BACKGROUND: Although body temperature is one of four key vital signs routinely
      monitored and treated in clinical practice, relatively little is known about the
      symptoms associated with febrile states. The purpose of this study was to assess
      the validity, reliability and feasibility of the Fever Assessment Tool (FAST) in
      an acute care research setting. METHODS: Qualitative: To assess content validity
      and finalize the FAST instrument, 12 adults from an inpatient medical-surgical
      unit at the National Institutes of Health (NIH) Clinical Center participated in
      cognitive interviews within approximately 12 h of a febrile state (tympanic
      temperature >= 38 degrees  Celsius). Quantitative: To test reliability, validity
      and feasibility, 56 new adult inpatients completed the 21-item FAST. RESULTS: The
      cognitive interviews clarified and validated the content of the final 21-item
      FAST. Fifty-six patients completed the FAST from two to 133 times during routine
      vital sign assessment, yielding 1,699 temperature time points. Thirty-four
      percent of the patients (N = 19) experienced fever at one or more time points,
      with a total of 125 febrile time points. Kuder-Richardson 20 (KR-20) reliability
      of the FAST was 0.70. Four nonspecific symptom categories, Tired or Run-Down
      (12), Sleepy (13), Weak or Lacking Energy (11), and Thirsty (9) were among the
      most frequently reported symptoms in all participants. Using Generalized
      Estimating Equations (GEE), the odds of reporting eight symptoms, Warm (4),
      Sweating (5), Thirsty (9), General Body Aches (10), Weak or Lacking Energy (11),
      Tired or Run Down (12) and Difficulty Breathing (17), were increased when
      patients had a fever (Fever Now), compared to the two other subgroups-patients
      who had a fever, but not at that particular time point, (Fever Not Now) and
      patients who never had a fever (Fever Never). Many, but not all, of the
      comparisons were significant in both groups. CONCLUSION: Results suggest the FAST
      is reliable, valid and easy to administer. In addition to symptoms usually
      associated with fever (e.g. feeling warm), symptoms such as Difficulty Breathing
      (17) were identified with fever. Further study in a larger, more diverse patient
      population is warranted. TRIAL REGISTRATION: Clinical Trials Number: NCT01287143
      (January 2011).

PMID- 28449676
TI  - Anti-inflammatory effect of combined tetramethylpyrazine, resveratrol and
      curcumin in vivo.
AB  - BACKGROUND: Resveratrol and curcumin, as natural flavones products, have good
      therapeutic effect in acute and chronic inflammation; on the other hand,
      tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well
      as anti-inflammatory function. In this paper, the anti-inflammatory effect of the
      tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and
      chronic inflammation was reported in vivo. METHODS: The dose of the combined
      three natural products was optimized based on the acute paw swelling mouse model
      with a Uniform Design methodology. The therapeutic effect of TRC combination on
      chronic inflammation was investigated by using the collagen-induced arthritis
      (CIA) rat model based upon the following indexes: the volume of paw swelling,
      arthritis score, serum mediators and histological examination as well as
      immunohistochemical staining. The levels of alanine aminotransferase (ALT) and
      aspartate transaminase (AST) in serum were measured and the pathological sections
      of liver and kidney were analysed. LD50 was measured based on the acute oral
      toxicity (AOT) standard method. RESULTS: The best formulation was the three
      components combined at the same mass proportion revealed by the Uniform Design
      methodology. This combination could significantly reduce the paw swelling in
      acute paw swelling mouse model, could reduce paw swelling and alleviate the
      damage in joint structural of ankle, cartilages and fibrous tissue in CIA rat
      model. The dose relationship was clear in both cases. Immunohistochemical
      staining of ankle tissue revealed that TRC combination was able to inhibit the
      expression of NF-kappaB p65 and TNF-alpha which were closely related to the
      inflammatory process. Analysis of serum mediators revealed TRC combination could
      inhibit the production of TNF-alpha, IL-1beta, and IL-6 in the serum. Toxic study
      revealed this formulation was low toxic, LD50 was larger than 5 g/kg, both the
      level of ALT and AST and histopathology in the liver and kidney exhibited no
      distinctions between the TRC combination and the blank group, no mortality
      occurred at the administered doses of 5 g/kg. CONCLUSIONS: The results showed
      this formulation could provide a novel potent treatment for acute and chronic
      inflammation (RA) without side effect like gastric injury occurring in NSAIDs.

PMID- 28449677
TI  - Cystic fibrosis: current therapeutic targets and future approaches.
AB  - OBJECTIVES: Study of currently approved drugs and exploration of future clinical
      development pipeline therapeutics for cystic fibrosis, and possible limitations
      in their use. METHODS: Extensive literature search using individual and a
      combination of key words related to cystic fibrosis therapeutics. KEY FINDINGS:
      Cystic fibrosis is an autosomal recessive disorder due to mutations in CFTR gene
      leading to abnormality of chloride channels in mucus and sweat producing cells.
      Respiratory system and GIT are primarily involved but eventually multiple organs
      are affected leading to life threatening complications. Management requires drug
      therapy, extensive physiotherapy and nutritional support. Previously, the focus
      was on symptomatic improvement and complication prevention but recently the
      protein rectifiers are being studied which are claimed to correct underlying
      structural and functional abnormalities. Some improvement is observed by the
      corrector drugs. Other promising approaches are gene therapy, targeting of
      cellular interactomes, and newer drugs for symptomatic improvement. CONCLUSIONS:
      The treatment has a long way to go as most of the existing therapeutics is for
      older children. Other limiting factors include mutation class, genetic profile,
      drug interactions, adverse effects, and cost. Novel approaches like gene
      transfer/gene editing, disease modeling and search for alternative targets are
      warranted.

PMID- 28449678
TI  - [18F]FDG PET/CT predicts progression-free survival in patients with idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating disease
      characterized by an unpredictable course. Prognostic markers and disease activity
      markers are needed. The purpose of this single-center retrospective study was to
      evaluate the prognostic value of lung fluorodeoxyglucose ([18F]-FDG) uptake
      assessed by standardized uptake value (SUV), metabolic lung volume (MLV) and
      total lesion glycolysis (TLG) in patients with IPF. METHODS: We included 27 IPF
      patients (IPF group) and 15 patients with a gastrointestinal neuroendocrine tumor
      without thoracic involvement (control group). We quantified lung SUV mean and SUV
      max, MLV and TLG and assessed clinical data, high-resolution CT (HRCT) fibrosis
      and ground-glass score; lung function; gender, age, physiology (GAP) stage at
      inclusion and during follow-up; and survival. RESULTS: Lung SUV mean and SUV max
      were higher in IPF patients than controls (p <0.00001). For patients with IPF,
      SUV mean, SUV max, MLV and TLG were correlated with severity of lung involvement
      as measured by a decline in forced vital capacity (FVC) and diffusing capacity of
      the lungs for carbon monoxide (DLCO) and increased GAP score. In a univariate and
      in a multivariate Cox proportional-hazards model, risk of death was increased
      although not significantly with high SUV mean. On univariate analysis, risk of
      death was significantly associated with high TLG and MLV, which disappeared after
      adjustment functional variables or GAP index. Increased MLV and TLG were
      independent predictors of death or disease progression during the 12 months after
      PET scan completion (for every 100-point increase in TLG, hazard ratio [HR]: 1.11
      (95% CI 1.06; 1.36), p = 0.003; for every 100-point increase in MLV, HR: 1.20
      (1.04; 1.19), p = 0.002). On multivariable analysis including TLG or MLV with
      age, FVC, and DLCO or GAP index, TLG and MLV remained associated with progression
      free survival (HR: 1.1 [1.03; 1.22], p = 0.01; and 1.13 [1.0; 1.2], p = 0.005).
      CONCLUSION: FDG lung uptake may be a marker of IPF severity and predict
      progression-free survival for patients with IPF.

PMID- 28449679
TI  - Change in children's physical activity and sedentary time between Year 1 and Year
      4 of primary school in the B-PROACT1V cohort.
AB  - BACKGROUND: The aim of this study was to examine how children's and parents'
      physical activity changes from Year 1 (5-6) to Year 4 (8-9 years of age).
      METHODS: Data are from the Bristol (UK) B-PROACT1V cohort. Fifty-seven primary
      schools were recruited when the children were in Year 1, with 1299 children and
      their parents providing data. Forty-seven schools were re-recruited in Year 4,
      with 1223 children and parents providing data (685 of whom participated in Year
      1). Children and at least one parent wore an accelerometer for 5 days including a
      weekend and mean minutes of sedentary time, moderate-to-vigorous intensity
      physical activity (MVPA) and accelerometer counts per minute (CPM) were derived.
      Multiple imputation was used to impute missing data for all 1837 families who
      took part, including those who participated at just one time. Paired t-tests
      examined if there was statistical evidence of change in accelerometer measures.
      RESULTS: Multiple imputation and observed data were comparable and results using
      complete observed data were mostly the same as those using imputed data. Imputed
      data showed that mean boys' CPM decreased from 747 to 673 (difference in mean 74
      [95% CI 45 to 103]) and girls' from 686 to 587 (99 [79 to 119]). Boys' time spent
      in MVPA reduced from 72 to 69 (3 [0 to 6]) and girls' from 62 to 56 (7 [4 to 9])
      minutes per day. There were increases in sedentary time for both boys (354 to 428
      min, 74 [61 to 88]) and girls (365 to 448, 83 [71 to 96]). There was no evidence
      of change in parent CPM or MVPA. Mothers' sedentary time increased by 26 min per
      day [16 to 35]. CONCLUSIONS: There were similar increases in sedentary time in
      girls and boys between age 5-6 and 8-9, and decreases in MVPA that were more
      marked in girls. The similarity of multiple-imputed and complete observed data
      suggest that these findings may not be markedly affected by selection bias.
      Result support early interventions to prevent the age-related decline in
      children's physical activity.

PMID- 28449680
TI  - The Health Literacy Questionnaire (HLQ) at the patient-clinician interface: a
      qualitative study of what patients and clinicians mean by their HLQ scores.
AB  - BACKGROUND: The Health Literacy Questionnaire (HLQ) has nine scales that each
      measure an aspect of the multidimensional construct of health literacy. All
      scales have good psychometric properties. However, it is the interpretations of
      data within contexts that must be proven valid, not just the psychometric
      properties of a measurement instrument. The purpose of this study was to
      establish the extent of concordance and discordance between individual patient
      and clinician interpretations of HLQ data in the context of complex case
      management. METHODS: Sixteen patients with complex needs completed the HLQ and
      were interviewed to discuss the reasons for their answers. Also, the clinicians
      of each of these patients completed the HLQ about their patient, and were
      interviewed to discuss the reasons for their answers. Thematic analysis of HLQ
      scores and interview data determined the extent of concordance between patient
      and clinician HLQ responses, and the reasons for discordance. RESULTS: Highest
      concordance (80%) between patient and clinician item-response pairs was seen in
      Scale 1 and highest discordance (56%) was seen in Scale 6. Four themes were
      identified to explain discordance: 1) Technical or literal meaning of specific
      words; 2) Patients' changing or evolving circumstances; 3) Different expectations
      and criteria for assigning HLQ scores; and 4) Different perspectives about a
      patient's reliance on healthcare providers. CONCLUSION: This study shows that the
      HLQ can act as an adjunct to clinical practice to help clinicians understand a
      patient's health literacy challenges and strengths early in a clinical encounter.
      Importantly, clinicians can use the HLQ to detect differences between their own
      perspectives about a patient's health literacy and the patient's perspective, and
      to initiate discussion to explore this. Provision of training to better detect
      these differences may assist clinicians to provide improved care. The outcomes of
      this study contribute to the growing body of international validation evidence
      about the use of the HLQ in different contexts. More specifically, this study has
      shown that the HLQ has measurement veracity at the patient and clinician level
      and may support clinicians to understand patients' health literacy and enable a
      deeper engagement with healthcare services.

PMID- 28449682
TI  - The determinants of dietary diversity and nutrition: ethnonutrition knowledge of
      local people in the East Usambara Mountains, Tanzania.
AB  - BACKGROUND: Diet and nutrition-related behaviours are embedded in cultural and
      environmental contexts: adoption of new knowledge depends on how easily it can be
      integrated into existing knowledge systems. As dietary diversity promotion
      becomes an increasingly common component of nutrition education, understanding
      local nutrition knowledge systems and local concepts about dietary diversity is
      essential to formulate efficient messages. METHODS: This paper draws on in-depth
      qualitative ethnographic research conducted in small-scale agricultural
      communities in Tanzania. Data were collected using interviews, focus group
      discussions and participant observation in the East Usambara Mountains, an area
      that is home primarily to the Shambaa and Bondei ethnic groups, but has a long
      history of ethnic diversity and ethnic intermixing. RESULTS: The data showed a
      high degree of consensus among participants who reported that dietary diversity
      is important because it maintains and enhances appetite across days, months and
      seasons. Local people reported that sufficient cash resources, agrobiodiversity,
      heterogeneity within the landscape, and livelihood diversity all supported their
      ability to consume a varied diet and achieve good nutritional status. Other
      variables affecting diet and dietary diversity included seasonality, household
      size, and gender. CONCLUSIONS: The results suggest that dietary diversity was
      perceived as something all people, both rich and poor, could achieve. There was
      significant overlap between local and scientific understandings of dietary
      diversity, suggesting that novel information on the importance of dietary
      diversity promoted through education will likely be easily integrated into the
      existing knowledge systems.

PMID- 28449681
TI  - Fin modules: an evolutionary perspective on appendage disparity in basal
      vertebrates.
AB  - BACKGROUND: Fishes are extremely speciose and also highly disparate in their fin
      configurations, more specifically in the number of fins present as well as their
      structure, shape, and size. How they achieved this remarkable disparity is
      difficult to explain in the absence of any comprehensive overview of the
      evolutionary history of fish appendages. Fin modularity could provide an
      explanation for both the observed disparity in fin configurations and the
      sequential appearance of new fins. Modularity is considered as an important
      prerequisite for the evolvability of living systems, enabling individual modules
      to be optimized without interfering with others. Similarities in developmental
      patterns between some of the fins already suggest that they form developmental
      modules during ontogeny. At a macroevolutionary scale, these developmental
      modules could act as evolutionary units of change and contribute to the disparity
      in fin configurations. This study addresses fin disparity in a phylogenetic
      perspective, while focusing on the presence/absence and number of each of the
      median and paired fins. RESULTS: Patterns of fin morphological disparity were
      assessed by mapping fin characters on a new phylogenetic supertree of fish
      orders. Among agnathans, disparity in fin configurations results from the
      sequential appearance of novel fins forming various combinations. Both median and
      paired fins would have appeared first as elongated ribbon-like structures, which
      were the precursors for more constricted appendages. Among chondrichthyans,
      disparity in fin configurations relates mostly to median fin losses. Among
      actinopterygians, fin disparity involves fin losses, the addition of novel fins
      (e.g., the adipose fin), and coordinated duplications of the dorsal and anal
      fins. Furthermore, some pairs of fins, notably the dorsal/anal and
      pectoral/pelvic fins, show non-independence in their character distribution,
      supporting expectations based on developmental and morphological evidence that
      these fin pairs form evolutionary modules. CONCLUSIONS: Our results suggest that
      the pectoral/pelvic fins and the dorsal/anal fins form two distinct evolutionary
      modules, and that the latter is nested within a more inclusive median fins
      module. Because the modularity hypotheses that we are testing are also supported
      by developmental and variational data, this constitutes a striking example
      linking developmental, variational, and evolutionary modules.

PMID- 28449683
TI  - Inhibition of NAMPT aggravates high fat diet-induced hepatic steatosis in mice
      through regulating Sirt1/AMPKalpha/SREBP1 signaling pathway.
AB  - BACKGROUND: Nonalcoholic fatty liver disease is one of the most common liver
      diseases in the world and is a typical hepatic manifestation of metabolic
      syndrome which is characterized with lipid accumulation in liver. Nicotinamide
      phosphoribosyltransferase (NAMPT) has been recently identified as an enzyme
      involved in nicotinamide adenine dinucleotide (NAD+) biosynthesis and plays an
      important role in cellular metabolism in variety of organs in mammals. The aim of
      this study was to investigate the effects of NAMPT on high fat diet-induced
      hepatic steatosis. METHODS: Hepatic steatosis model was induced by high fat diet
      (HFD) in C57BL/6 mice in vivo. HepG2 and Hep1-6 hepatocytes were transfected with
      NAMPT vector plasmid or treated with NAMPT inhibitor FK866 and then incubated
      with oleic acid. Lipids accumulation was examined by HE staining or oil red
      staining. Quantitative RT-PCR and Western blot were used to measure expressions
      of the genes involved in lipogenic synthesis. RESULTS: FK866 significantly
      promoted liver steatosis in the mice fed with HFD and hepatic lipid accumulation
      in vitro, accompanied by the increases of the expressions of lipogenic genes such
      as sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase
      (FASN). Nicotinamide mononucleotide (NMN) and NAD+ significantly rescued the
      actions of FK866 in vitro. In contrast, overexpression of NAMPT in HepG2 and Hep1
      6 hepatocytes ameliorated hepatic lipid accumulation. In addition, FK866
      decreased the protein levels of Sirt1 and phospho-AMPKalpha in liver of the HFD
      fed mice. Furthermore, Resveratrol, a Sirt1 activator, significantly reduced
      lipogenic gene expressions, while EX-527, a Sirt1 specific inhibitor, had the
      opposite effects. CONCLUSION: Our results demonstrated that inhibition of NAMPT
      aggravated the HFD- or oleic acid-induced hepatic steatosis through suppressing
      Sirt1-mediated signaling pathway. On the one hand, the inhibition of NAMPT
      reduced the production of NAD+ through inhibiting the NAD+ salvage pathway,
      resulting in the decrease of Sirt1 activity, and then attenuated the
      deacetylation of SREBP1 in which the inhibition of SREBP1 activity promoted the
      expressions of FASN and ACC. On the other hand, the reduced Sirt1 activity
      alleviated the activation of AMPKalpha to further enhance SREBP1 activities.

PMID- 28449684
TI  - Reducing the metabolic cost of walking with an ankle exoskeleton: interaction
      between actuation timing and power.
AB  - BACKGROUND: Powered ankle-foot exoskeletons can reduce the metabolic cost of
      human walking to below normal levels, but optimal assistance properties remain
      unclear. The purpose of this study was to test the effects of different
      assistance timing and power characteristics in an experiment with a tethered
      ankle-foot exoskeleton. METHODS: Ten healthy female subjects walked on a
      treadmill with bilateral ankle-foot exoskeletons in 10 different assistance
      conditions. Artificial pneumatic muscles assisted plantarflexion during ankle
      push-off using one of four actuation onset timings (36, 42, 48 and 54% of the
      stride) and three power levels (average positive exoskeleton power over a stride,
      summed for both legs, of 0.2, 0.4 and 0.5 W?kg-1). We compared metabolic rate,
      kinematics and electromyography (EMG) between conditions. RESULTS: Optimal
      assistance was achieved with an onset of 42% stride and average power of 0.4 W?kg
      1, leading to 21% reduction in metabolic cost compared to walking with the
      exoskeleton deactivated and 12% reduction compared to normal walking without the
      exoskeleton. With suboptimal timing or power, the exoskeleton still reduced
      metabolic cost, but substantially less so. The relationship between timing, power
      and metabolic rate was well-characterized by a two-dimensional quadratic
      function. The assistive mechanisms leading to these improvements included
      reducing muscular activity in the ankle plantarflexors and assisting leg swing
      initiation. CONCLUSIONS: These results emphasize the importance of optimizing
      exoskeleton actuation properties when assisting or augmenting human locomotion.
      Our optimal assistance onset timing and average power levels could be used for
      other exoskeletons to improve assistance and resulting benefits.

PMID- 28449685
TI  - Development and psychometric testing of an instrument to compare career choice
      influences and perceptions of nursing among healthcare students.
AB  - BACKGROUND: With the availability of more healthcare courses and an increased
      intake of nursing students, education institutions are facing challenges to
      attract school leavers to enter nursing courses. The comparison of career choice
      influences and perception of nursing among healthcare students can provide
      information for recruitment strategies. An instrument to compare the influences
      of healthcare career choice is lacking. The purpose of this study is to develop
      and evaluate the psychometric properties of an instrument to compare the
      influences of healthcare career choice with perceptions of nursing as a career
      choice. METHODS: The study was conducted in two phases. In phase one, two sets of
      scales with parallel items that measure the influences of healthcare career
      choice and perceptions of nursing as a career choice were developed through an
      earlier qualitative study, literature review, and expert validation. Phase two
      involved testing the construct validity, concurrent validity and reliability with
      a convenience sample of 283 first year healthcare students who were recruited at
      two education institutions in Singapore. RESULTS: An exploratory factor analysis
      revealed 35-parallel items in a six-factor solution (personal interest, prior
      healthcare exposure, self-efficacy, perceived nature of work, job prospects, and
      social influences) that explained 59 and 64% of the variance for healthcare
      career choice and nursing as a career choice respectively. A high correlation (r
      = 0.76, p < 0.001) was obtained with an existing tool, confirming the concurrent
      validity. The internal consistency was sufficient with Cronbach's alpha of 0.93
      for healthcare career choice and 0.94 for nursing as a career choice. The test
      retest reliability was acceptable with an Intraclass Correlation Coefficient of
      0.63 for healthcare career choice and 0.60 for nursing as a career choice.
      CONCLUSIONS: The instrument provides opportunities for understanding the
      differences between influences of healthcare career choice and perceptions of
      nursing as a career choice. This comparative understanding of career choice
      influences can guide educator and policy-makers on nursing recruitment.

PMID- 28449686
TI  - The frequency of asthma exacerbations and healthcare utilization in patients with
      asthma from the UK and USA.
AB  - BACKGROUND: Asthma exacerbations are frequent in patients with severe disease.
      This report describes results from two retrospective cohort studies describing
      exacerbation frequency and risk, emergency department (ED)/hospital re
      admissions, and asthma-related costs by asthma severity in the US and UK.
      METHODS: Patients with asthma in the US-based ClinformaticsTM DataMart Multiplan
      IMPACT (2010-2011; WEUSKOP7048) and the UK-based Clinical Practice Research
      Datalink (2009-2011; WEUSKOP7092) databases were categorized by disease severity
      (Global Initiative for Asthma [GINA]; Step and exacerbation history) during the
      12 months pre-asthma medical code (index date). Outcomes included: frequency of
      exacerbations (asthma-related ED visit, hospitalization, or oral corticosteroid
      use with an asthma medical code recorded within +/-2 weeks) 12 months post-index,
      asthma-related ED visits/hospitalization, and asthma-related costs 30 days post
      index. Risk of a subsequent exacerbation was determined by proportional hazard
      model. RESULTS: Of the 222,817 and 211,807 patients with asthma included from the
      US and UK databases, respectively, 12.5 and 8.4% experienced >=1 exacerbation
      during the follow-up period. Exacerbation frequency increased with disease
      severity. Among the 5,167 and 2,904 patients with an asthma-related ED
      visit/hospitalization in the US and UK databases, respectively, 9.2 and 4.7% had
      asthma-related re-admissions within 30 days. Asthma-related re-admission rates
      and costs increased with disease severity, approximately doubling between GINA
      Step 1 and 5 and in patients with >=2 versus <2 exacerbations in the previous
      year. Risk of a subsequent exacerbation increased 32-35% for an exacerbation
      requiring ED visit/hospitalization versus oral corticosteroids. CONCLUSION:
      Increased disease severity was associated with higher exacerbation frequency,
      ED/hospitalization re-admission, costs and risk of subsequent exacerbation,
      indicating that these patients require high-intensity post-exacerbation
      management.

PMID- 28449687
TI  - Expression and clinicopathologic significance of TUFM and p53 for the normal
      adenoma-carcinoma sequence in colorectal epithelia.
AB  - BACKGROUND: Evidence indicates that most cases of colorectal carcinoma (CRC)
      develop from adenoma. A previous study demonstrated that mitochondrial Tu
      translation elongation factor (TUFM) might serve as an independent prognostic
      factor for colorectal cancer. However, the expression and function of TUFM in the
      normal-adenoma-cancer sequence have not been reported. In this study, we
      investigated the clinicopathologic significance of TUFM and p53 expression for
      the normal-adenoma-carcinoma sequence in colorectal epithelia and evaluated the
      roles of TUFM during the progression of colorectal tumors. METHODS: Paraffin
      embedded specimens from 261 colorectal normal mucosa samples, 157 adenomas, and
      104 early carcinomas were analyzed for TUFM and p53 expression by
      immunohistochemistry. RESULTS: Expression of TUFM and p53 was significantly
      increased during the colorectal normal-adenoma-carcinoma sequence (all P < 0.05).
      The expression of TUFM and p53 was associated with histologic type of adenomas (P
      = 0.028; P = 0.001) and grade of dysplasia (all P = 0.001). Expression of TUFM
      was positively correlated with that of p53 (r = 0.319, P = 0.001). CONCLUSIONS:
      Upregulated TUFM expression may play an important role in the transformation from
      colorectal normal mucosa to carcinoma through adenoma. Combined
      immunohistochemical detection of TUFM and p53 may be useful for evaluating the
      biological behavior of colorectal adenoma.

PMID- 28449689
TI  - On classifying the field of medical ethics.
AB  - In 2014, the editorial board of BMC Medical Ethics came together to devise
      sections for the journal that would (a) give structure to the journal (b) help
      ensure that authors' research is matched to the most appropriate editors and (c)
      help readers to find the research most relevant to them. The editorial board
      decided to take a practical approach to devising sections that dealt with the
      challenges of content management. After that, we started thinking more
      theoretically about how one could go about classifying the field of medical
      ethics. This editorial elaborates and reflects on the practical approach that we
      took at the journal, then considers an alternative theoretically derived
      approach, and reflects on the possibilities, challenges and value of classifying
      the field more broadly.

PMID- 28449688
TI  - YY-1224, a terpene trilactone-strengthened Ginkgo biloba, attenuates
      neurodegenerative changes induced by beta-amyloid (1-42) or double transgenic
      overexpression of APP and PS1 via inhibition of cyclooxygenase-2.
AB  - BACKGROUND: Ginkgo biloba has been reported to possess free radical-scavenging
      antioxidant activity and anti-inflammatory properties. In our pilot study, YY
      1224, a terpene trilactone-strengthened extract of G. biloba, showed anti
      inflammatory, neurotrophic, and antioxidant effects. RESULTS: We investigated the
      pharmacological potential of YY-1224 in beta-amyloid (Abeta) (1-42)-induced
      memory impairment using cyclooxygenase-2 (COX-2) knockout (-/-) and APPswe/PS1dE9
      transgenic (APP/PS1 Tg) mice. Repeated treatment with YY-1224 significantly
      attenuated Abeta (1-42)-induced memory impairment in COX-2 (+/+) mice, but not in
      COX-2 (-/-) mice. YY-1224 significantly attenuated Abeta (1-42)-induced
      upregulation of platelet-activating factor (PAF) receptor gene expression,
      reactive oxygen species, and pro-inflammatory factors. In addition, YY-1224
      significantly inhibited Abeta (1-42)-induced downregulation of PAF
      acetylhydrolase-1 (PAF-AH-1) and peroxisome proliferator-activated receptor gamma
      (PPARgamma) gene expression. These changes were more pronounced in COX-2 (+/+)
      mice than in COX-2 (-/-) mice. YY-1224 significantly attenuated learning
      impairment, Abeta deposition, and pro-inflammatory microglial activation in
      APP/PS1 Tg mice, whereas it significantly enhanced PAF-AH and PPARgamma
      expression. A preferential COX-2 inhibitor, meloxicam, did not affect the
      pharmacological activity by YY-1224, suggesting that the COX-2 gene is a critical
      mediator of the neuroprotective effects of YY-1224. The protective activity of YY
      1224 appeared to be more efficacious than a standard G. biloba extract (Gb)
      against Abeta insult. CONCLUSIONS: Our results suggest that the protective
      effects of YY-1224 against Abeta toxicity may be associated with its PAF
      antagonistic- and PPARgamma agonistic-potential as well as inhibition of the
      Abeta-mediated pro-inflammatory switch of microglia phenotypes through
      suppression of COX-2 expression.

PMID- 28449690
TI  - Daily home fortification with iron as ferrous fumarate versus NaFeEDTA: a
      randomised, placebo-controlled, non-inferiority trial in Kenyan children.
AB  - BACKGROUND: We aimed to show the non-inferiority of home fortification with a
      daily dose of 3 mg iron in the form of iron as ferric sodium
      ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated
      ferrous fumarate in Kenyan children aged 12-36 months. In addition, we updated a
      recent meta-analysis to assess the efficacy of home fortification with iron
      containing powders, with a view to examining diversity in trial results. METHODS:
      We gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and
      praziquantel to 338 afebrile children with haemoglobin concentration >=70 g/L. We
      randomly allocated them to daily home fortification for 30 days with either
      placebo, 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate.
      We assessed haemoglobin concentration (primary outcome), plasma iron markers,
      plasma inflammation markers and Plasmodium infection in samples collected at
      baseline and after 30 days of intervention. We conducted a meta-analysis of
      randomised controlled trials in pre-school children to assess the effect of home
      fortification with iron-containing powders on anaemia and haemoglobin
      concentration at end of intervention. RESULTS: A total of 315 children completed
      the 30-day intervention period. At baseline, 66.9% of children had inflammation
      (plasma C-reactive protein concentration >5 mg/L or plasma alpha 1-acid
      glycoprotein concentration >1.0 g/L); in those without inflammation, 42.5% were
      iron deficient. There was no evidence, either in per protocol analysis or
      intention-to-treat analysis, that home fortification with either of the iron
      interventions improved haemoglobin concentration, plasma ferritin concentration,
      plasma transferrin receptor concentration or erythrocyte zinc protoporphyrin-haem
      ratio. We also found no evidence of effect modification by iron status, anaemia
      status and inflammation status at baseline. In the meta-analysis, the effect on
      haemoglobin concentration was highly heterogeneous between trials (I 2: 84.1%; p
      value for test of heterogeneity: <0.0001). CONCLUSIONS: In this population, home
      fortification with either 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated
      ferrous fumarate was insufficiently efficacious to assess non-inferiority of 3 mg
      iron as NaFeEDTA compared to 12.5 mg iron as encapsulated ferrous fumarate. Our
      finding of heterogeneity between trial results should stimulate subgroup analysis
      or meta-regression to identify population-specific factors that determine
      efficacy. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (
      NCT02073149 ) on 25 February 2014.

PMID- 28449692
TI  - Clinical and demographic factors associated with change and maintenance of
      disease severity in a large registry of patients with rheumatoid arthritis.
AB  - BACKGROUND: We examined models to predict disease activity transitions from
      moderate to low or severe and associated factors in patients with rheumatoid
      arthritis (RA). METHODS: Data from RA patients enrolled in the Corrona registry
      (October 2001 to August 2014) were analyzed. Clinical Disease Activity Index
      (CDAI) definitions were used for low (<=10), moderate (>10 and <=22), and severe
      (>22) disease activity states. A Markov model for repeated measures allowing for
      covariate dependence was used to model transitions between three (low, moderate,
      severe) states and estimate population transition probabilities. Mean sojourn
      times were calculated to compare length of time in particular states. Logistic
      regression models were used to examine impacts of covariates (time between
      visits, chronological year, disease duration, age) on disease states. RESULTS:
      Data from 29,853 patients (251,375 visits) and a sub-cohort of 9812 patients
      (46,534 visits) with regular visits (every 3-9 months) were analyzed. The
      probability of moving from moderate to low or severe disease by next visit was
      47% and 18%, respectively. Patients stayed in moderate disease for mean 4.25
      months (95% confidence interval: 4.18-4.32). Transition probabilities showed 20%
      of patients with low disease activity moved to moderate or severe disease within
      6 months; >35% of patients with moderate disease remained in moderate disease
      after 6 months. Results were similar for the regular-visit sub-cohort.
      Significant interactions with prior disease state were seen with chronological
      year and disease duration. CONCLUSION: A substantial proportion of patients
      remain in moderate disease, emphasizing the need for treat-to-target strategies
      for RA patients.

PMID- 28449691
TI  - The impact of rare and low-frequency genetic variants in common disease.
AB  - Despite thousands of genetic loci identified to date, a large proportion of
      genetic variation predisposing to complex disease and traits remains unaccounted
      for. Advances in sequencing technology enable focused explorations on the
      contribution of low-frequency and rare variants to human traits. Here we review
      experimental approaches and current knowledge on the contribution of these
      genetic variants in complex disease and discuss challenges and opportunities for
      personalised medicine.

PMID- 28449693
TI  - No measurable adverse effects of Lassa, Morogoro and Gairo arenaviruses on their
      rodent reservoir host in natural conditions.
AB  - BACKGROUND: In order to optimize net transmission success, parasites are
      hypothesized to evolve towards causing minimal damage to their reservoir host
      while obtaining high shedding rates. For many parasite species however this
      paradigm has not been tested, and conflicting results have been found regarding
      the effect of arenaviruses on their rodent host species. The rodent Mastomys
      natalensis is the natural reservoir host of several arenaviruses, including Lassa
      virus that is known to cause Lassa haemorrhagic fever in humans. Here, we
      examined the effect of three arenaviruses (Gairo, Morogoro and Lassa virus) on
      four parameters of wild-caught Mastomys natalensis: body mass, head-body length,
      sexual maturity and fertility. After correcting for the effect of age, we
      compared these parameters between arenavirus-positive (arenavirus RNA or
      antibody) and negative animals using data from different field studies in Guinea
      (Lassa virus) and Tanzania (Morogoro and Gairo viruses). RESULTS: Although the
      sample sizes of our studies (1297, 749 and 259 animals respectively) were large
      enough to statistically detect small differences in body conditions, we did not
      observe any adverse effects of these viruses on Mastomys natalensis. We did find
      that sexual maturity was significantly positively related with Lassa virus
      antibody presence until a certain age, and with Gairo virus antibody presence in
      general. Gairo virus antibody-positive animals were also significantly heavier
      and larger than antibody-free animals. CONCLUSION: Together, these results
      suggest that the pathogenicity of arenaviruses is not severe in M. natalensis,
      which is likely to be an adaptation of these viruses to optimize transmission
      success. They also suggest that sexual behaviour might increase the probability
      of M. natalensis to become infected with arenaviruses.

PMID- 28449694
TI  - The MHC locus and genetic susceptibility to autoimmune and infectious diseases.
AB  - In the past 50 years, variants in the major histocompatibility complex (MHC)
      locus, also known as the human leukocyte antigen (HLA), have been reported as
      major risk factors for complex diseases. Recent advances, including large genetic
      screens, imputation, and analyses of non-additive and epistatic effects, have
      contributed to a better understanding of the shared and specific roles of MHC
      variants in different diseases. We review these advances and discuss the
      relationships between MHC variants involved in autoimmune and infectious
      diseases. Further work in this area will help to distinguish between alternative
      hypotheses for the role of pathogens in autoimmune disease development.

PMID- 28449696
TI  - Perioperative adjuvant corticosteroids for post-operative analgesia in elective
      knee surgery - A systematic review.
AB  - BACKGROUND: Elective knee surgery is performed to reduce chronic pain and improve
      function in degenerate knees. Treatment of acute post-operative pain is
      suboptimal in 75% of patients despite multimodal analgesic approaches resulting
      in higher post-operative opiate consumption. The effect of corticosteroids as an
      adjunct for post-operative pain control remains undefined. METHODS: The databases
      MEDLINE, EMBASE and CENTRAL (Cochrane library) will be searched from their
      inception to present using broad search criteria for eligible randomised/quasi
      randomised controlled trials investigating perioperative corticosteroid
      adjunctive use in elective knee surgery. Meta-analyses will be conducted
      according to the recommendations from the Cochrane Handbook for Systematic
      Reviews of Interventions. DISCUSSION: This systematic review of the perioperative
      adjunctive use of corticosteroids will assess the analgesic effects, post
      operative nausea and vomiting, opiate consumption, infection rates and time till
      discharge and assess whether adjunctive corticosteroids should be encouraged in
      elective knee surgery. SYSTEMATIC REVIEW REGISTRATION: PROPSERO CRD42016049336.

PMID- 28449695
TI  - Intermediate uveitis: pattern of etiology, complications, treatment and outcome
      in a tertiary academic center.
AB  - BACKGROUND: Patients with intermediate uveitis (IU) represent a heterogenous
      group characterized by a wide spectrum of etiologies and regional differences.
      Aim of the study was to analyze the characteristics of patients with IU examined
      in an academic center in Germany. METHODS: We conducted a retrospective analysis
      of the clinical records of all patients with intermediate uveitis referred to the
      Eye Center, University of Freiburg from 2007 to 2014. Diagnosis followed the
      Standardization in Uveitis Nomenclature (SUN) criteria. Data analysis included:
      etiology of IU, demographics, complications, treatment and visual acuity.
      RESULTS: We identified 159 patients with intermediate uveitis during that period.
      Mean age at diagnosis was 35 years. Most are female (64%), and the mean duration
      of IU was 6.1 years (range 1 month - 35 years). Etiology of IU was idiopathic in
      59%. Multiple sclerosis (MS) (20%) and sarcoidosis (10%) were frequent systemic
      causes of IU. Other etiologies including infectious diseases (tuberculosis,
      borreliosis) or immune-mediated conditions (eg, after vaccination) were present
      in 11%. The pattern of complications included macular edema (CME) (36%), cataract
      (24%), secondary glaucoma (7%), and epiretinal membrane formation (19%).
      Periphlebitis and optic neuritis were more frequent in conjunction with MS.
      Treatment comprised local and systemic steroids, immunosuppressive agents,
      biologics, and surgery. Best corrected visual acuity was better than 20/25 in 60%
      of the eyes after more than 10 years of follow-up. CONCLUSIONS: In our German
      academic center, most IU cases were idiopathic or associated with MS or
      sarcoidosis. In contrast to other countries, infectious cases were rare.
      Patients' overall visual prognosis is favorable even when the duration of IU has
      been long and and despite numerous complications.

PMID- 28449697
TI  - Teaching implementation science in a new Master of Science Program in Germany: a
      survey of stakeholder expectations.
AB  - BACKGROUND: Implementation science in healthcare is an evolving discipline in
      German-speaking countries. In 2015, the Medical Faculty of the University of
      Heidelberg, Germany, implemented a two-year full-time Master of Science program
      Health Services Research and Implementation Science. The curriculum introduces
      implementation science in the context of a broader program that also covers
      health services research, healthcare systems, research methods, and generic
      academic skills. Our aim was to assess the expectations of different stakeholder
      groups regarding the master's program. METHODS: An online survey listing desired
      competencies of prospective graduates was developed and administered to four
      groups: national experts in the field (including potential employers of
      graduates), teaching staff, enrolled students, and prospective students (N =
      169). Competencies were extracted from the curriculum's module handbook. A five
      point Likert scale was used for the assessment of 42 specific items. Data were
      analyzed descriptively. RESULTS: A total of 83 people participated in the survey
      (response rate 49%). The online survey showed a strong agreement across the
      groups concerning the desired competencies of graduates. About two-thirds of the
      listed competencies (27 items) were felt to be crucial or very important by 80%
      or more of participants, with little difference between stakeholder groups. Of
      the eight items specifically related to implementation in practice, six were in
      this category. Knowledge of implementation strategies (90% very important),
      knowledge of barriers and enablers of implementation (89%), and knowledge of
      evidence-based practice (89%) were the top priorities. CONCLUSIONS: The master's
      program is largely orientated towards the desired competencies of graduates
      according to students, teaching staff, and national experts.

PMID- 28449698
TI  - Setup errors in patients with head-neck cancer (HNC), treated using the Intensity
      Modulated Radiation Therapy (IMRT) technique: how it influences the customised
      immobilisation systems, patient's pain and anxiety.
AB  - BACKGROUND: In patients with head-neck cancer treated with IMRT, immobility of
      the upper part of the body during radiation is maintained by means of customised
      immobilisation devices. The main purpose of this study was to determine how the
      procedures for preparation of customised immobilisation systems and the patients
      characteristics influence the extent of setup errors. METHODS: A longitudinal,
      prospective study involving 29 patients treated with IMRT. Data were collected
      before CT simulation and during all the treatment sessions (528 setup errors
      analysed overall); the correlation with possible risk factors for setup errors
      was explored using a linear mixed model. RESULTS: Setup errors were not
      influenced by the patient's anxiety and pain. Temporary removal of the
      thermoplastic mask before carrying out the CT simulation shows statistically
      borderline, clinically relevant, increase of setup errors (+24.7%, 95% CI: -0.5% 
      55.8%). Moreover, a unit increase of radiation therapists who model the
      customised thermoplastic mask is associated to a -18% (-29.2% - -4.9%) reduction
      of the errors. The setup error is influenced by the patient's physical features;
      in particular, it increases both in patients in whom the treatment position is
      obtained with 'Shoulder down' (+27.9%, 2.2% - 59.7%) and in patients with
      'Scoliosis/kyphosis' problems (+65.4%, 2.3% - 164.2%). Using a 'Small size
      standard plus customized neck support device' is associated to a -52.3% (-73.7% -
      -11.2%) reduction. The increase in number of radiation therapists encountered
      during the entire treatment cycle does not show associations. Increase in the
      body mass index is associated with a slight reduction in setup error by (-2.8%, 
      5% - -0.7%). CONCLUSION: The position of the patient obtained by forcing the
      shoulders downwards, clinically significant scoliosis or kyphosis and the
      reduction of the number of radiation therapists who model the thermoplastic mask
      are found to be statistically significant risk factors that can cause an increase
      in setup errors, while the use of 'Small size' neck support device and patient
      BMI can diminish them.

PMID- 28449699
TI  - Shoe-stiffening inserts for first metatarsophalangeal joint osteoarthritis (the
      SIMPLE trial): study protocol for a randomised controlled trial.
AB  - BACKGROUND: This article describes the design of a parallel-group, participant-
      and assessor-blinded randomised controlled trial comparing the effectiveness of
      shoe-stiffening inserts versus sham shoe insert(s) for reducing pain associated
      with first metatarsophalangeal joint (MTPJ) osteoarthritis (OA). METHODS: Ninety
      participants with first MTPJ OA will be randomised to receive full-length shoe
      stiffening insert(s) (Carbon Fibre Spring Plate, Paris Orthotics, Vancouver, BC,
      Canada) plus rehabilitation therapy or sham shoe insert(s) plus rehabilitation
      therapy. Outcome measures will be obtained at baseline, 4, 12, 24 and 52 weeks;
      the primary endpoint for assessing effectiveness being 12 weeks. The primary
      outcome measure will be the foot pain domain of the Foot Health Status
      Questionnaire (FHSQ). Secondary outcome measures will include the function domain
      of the FHSQ, severity of first MTPJ pain (using a 100-mm Visual Analogue Scale),
      global change in symptoms (using a 15-point Likert scale), health status (using
      the Short-Form-12(r) Version 2.0 and EuroQol (EQ-5D-5LTM) questionnaires), use of
      rescue medication and co-interventions, self-reported adverse events and physical
      activity levels (using the Incidental and Planned Activity Questionnaire). Data
      will be analysed using the intention-to-treat principle. Economic analysis (cost
      effectiveness and cost-utility) will also be performed. In addition, the
      kinematic effects of the interventions will be examined at 1 week using a three
      dimensional motion analysis system and multisegment foot model. DISCUSSION: This
      study will determine whether shoe-stiffening inserts are a cost-effective
      intervention for relieving pain associated with first MTPJ OA. The biomechanical
      analysis will provide useful insights into the mechanism of action of the shoe
      stiffening inserts. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry, identifier: ACTRN12616000552482 . Registered on 28 April 2016.

PMID- 28449700
TI  - Determinants of impaired quality of life in patients with fibrous dysplasia.
AB  - BACKGROUND: Fibrous dysplasia is a rare bone disorder, commonly associated with
      pain, deformity and fractures, which may significantly impact on quality of life.
      In this study we evaluate quality of life in patients with fibrous dysplasia
      using the Short Form-36 and the Brief Pain Inventory questionnaires. Data were
      compared with those of the general Dutch population. RESULTS: Out of 138 patients
      from a cohort of 255 patients with fibrous dysplasia that were sent
      questionnaires assessing quality of life and pain, the response rate was 70.3%,
      with 97 patients, predominantly female (65%), completing the questionnaires.
      Monostotic fibrous dysplasia was predominant (n = 62, 64%). Fibrous dysplasia
      patients had significantly lower quality of life outcome scores than the general
      Dutch population for all tested domains of the Short Form-36 except for the
      "Mental health" and the "Role emotional" domains. More severe forms of fibrous
      dysplasia, had the more severe Short-Form-36 quality of life outcomes, but there
      was no significant difference in Brief Pain Inventory domains between different
      subtypes of fibrous dysplasia. Quality of life was lower in patients with higher
      disease burden, as reflected by high skeletal burden scores (p = 0.003) and high
      levels of P1NP (p = 0.002). CONCLUSION: We demonstrate impairments in all domains
      of quality of life, except for 'Mental health' and 'Role emotional' domains,
      across the wide spectrum of fibrous dysplasia including its milder forms. We
      identified high skeletal burden scores, reflecting disease severity, as the most
      consistent predictor of impaired quality of life. Our findings hold significant
      clinical implications as they draw attention to the clinically unmet need to
      address quality of life issues in the management of patients with all subtypes of
      fibrous dysplasia, including its milder forms.

PMID- 28449701
TI  - Arthroscopic treatment of focal osteochondral lesions of the first
      metatarsophalangeal joint.
AB  - BACKGROUND: Although arthroscopic surgical treatment of the first
      metatarsophalangeal (MTP) joint involves painful sesamoid excision, synovectomy,
      debridement, and partial cheilectomy, no gold standard treatment technique has
      been defined in the literature for hallux rigidus and focal osteochondral
      lesions. This study aimed to assess the arthroscopic treatment for early grade
      focal osteochondral lesions of the first MTP joint and to determine the impact of
      arthroscopic microhole drill surgery on foot function and activities of daily
      living in a group of patients who failed conservative treatment. METHODS: This
      prospective study included 14 patients with hallux rigidus and focal
      osteochondral lesions of the first MTP joint who underwent surgery in 2014 and
      were followed on a regular basis thereafter. RESULTS: The patients had mean
      preoperative VPS (visual pain score) and AOFAS (American Orthopedic Foot and
      ankle Society)-Hallux scores of 8.14 +/- 0.86 SD and 48.64 +/- 4.27,
      respectively; the corresponding postoperative values of both scores were 1.86 +/-
      0.66 SD and 87.00 +/- 3.70. Both VPS and AOFAS-Hallux scores changed
      significantly. DISCUSSION: In this prospective study, we explored the impact of
      arthroscopic microhole drill surgery on foot function and activities of daily
      living in patients with focal osteochondral lesions of the first MTP joint. Our
      results showed significant improvements in VPS and AOFAS scores with this
      treatment. CONCLUSIONS: An arthroscopic microhole drill technique can be used
      with impressive functional scores and without any complications in patients who
      failed conservative therapy for hallux rigidus with focal chondral injury.

PMID- 28449702
TI  - Quantification of renal function following stereotactic body radiotherapy for
      pancreatic cancer: secondary dosimetric analysis of a prospective clinical trial.
AB  - BACKGROUND: This is the first known study examining renal function following
      stereotactic body radiotherapy (SBRT) for pancreatic head adenocarcinoma.
      METHODS: Thirty-eight borderline-resectable/unresectable patients, part of an
      ongoing prospective trial, underwent 3 cycles of gemcitabine/5-fluorouracil
      followed by SBRT (5 daily fractions of 5/6/7/8 Gy) and concurrent nelfinavir.
      Thereafter, in resectable cases, surgery was performed within 4-8 weeks. The last
      available pre-SBRT creatinine was recorded, along with the highest post-SBRT
      value. Glomerular filtration rate (GFR) was calculated by the commonly-utilized
      Modification of Diet in Renal Disease formula. GFR decline was defined as the
      post-SBRT nadir GFR minus the pre-SBRT GFR. Correlations with the V5-V30, and
      mean/maximum kidney doses was performed. Statistics included Pearson correlation,
      Mann-Whitney, and Fisher's exact tests. RESULTS: The median total kidney volume
      was 355 cm3. Median dosimetric values were as follows: V5 (209 cm3), V10 (103
      cm3), V15 (9 cm3), V20 (0 cm3), V25 (0 cm3); and mean (6.7 Gy) & maximum kidney
      dose (18.3 Gy). Median GFR change was -23 (range, -105 to 25) mL/min/1.73 cm2. Of
      all dosimetric parameters, only V5 was significantly associated with changes in
      GFR (Pearson r = -0.40, p = 0.012). In patients with V5 < 210 cm3, median GFR
      change was -11.8 mL/min/1.73 cm2, as compared with -37.1 mL/min/1.73 cm2 change
      in those with V5 >= 210 cm3 (p = 0.02). A GFR change < -23 mL/min/1.73 cm2 was
      observed in 6/20 (30%) patients with V5 < 210 cm3, versus 15/18 (83%) of those
      with V5 >= 210 cm3. Patients with V5 >= 210 cm3 were over ten times as likely to
      have GFR change < -23 mL/min/1.73 cm2 (p = 0.003). Using linear regression, GFR
      change ~ -0.1748 * V5(cm3) + 8.63. CONCLUSIONS: In the first known analysis of
      renal function after pancreatic SBRT, evaluating patients on a prospective study,
      V5 >= 210 cm3 was associated with a post-SBRT GFR decline of >23 mL/min/1.73 cm2.
      If V5 is kept <210 cm3, median GFR decline was only 11.8 mL/min/1.73 cm2. Further
      validation is needed to ascertain definite dose-volume parameters and examine
      late renal decline.

PMID- 28449703
TI  - A short time interval between radiotherapy and hyperthermia reduces in-field
      recurrence and mortality in women with advanced cervical cancer.
AB  - BACKGROUND: Combined radiotherapy and hyperthermia is a well-established
      alternative to chemoradiotherapy for advanced stage cervical cancer patients with
      a contraindication for chemotherapy. Pre-clinical evidence suggests that the
      radiosensitizing effect of hyperthermia decreases substantially for time
      intervals between radiotherapy and hyperthermia as short as 1-2 h, but clinical
      evidence is limited. The purpose of this study is to determine the effect of the
      time interval between external beam radiotherapy (EBRT) and same-day hyperthermia
      on in-field recurrence rate, overall survival and late toxicity in women with
      advanced stage cervical cancer. METHODS: Patients with advanced stage cervical
      cancer who underwent a full-course of curative daily EBRT and (4-5) weekly
      hyperthermia sessions between 1999 and 2014 were included for retrospective
      analysis. The mean time interval between EBRT fractions and same-day hyperthermia
      was calculated for each patient; the median thereof was used to divide the cohort
      in a 'short' and 'long' time-interval group. Kaplan-Meier analysis and stepwise
      Cox regression were used to compare the in-field recurrence and overall survival.
      Finally, high-grade (>=3) late toxicity was compared across time-interval groups.
      DNA repair suppression is an important hyperthermia mechanism, DNA damage repair
      kinetics were therefore studied in patient biopsies to support clinical findings.
      RESULTS: Included were 58 patients. The 3-year in field recurrence rate was 18%
      and 53% in the short (<=79.2 min) and long (>79.2 min) time-interval group,
      respectively (p = 0.021); the 5-year overall survival was 52% and 17%
      respectively (p = 0.015). Differences between time-interval groups remained
      significant for both in-field recurrence (HR = 7.7, p = 0.007) and overall
      survival (HR = 2.3, p = 0.012) in multivariable Cox regression. No difference in
      toxicity was observed (p = 1.00), with only 6 and 5 events in the short and long
      group, respectively. The majority of DNA damage was repaired within 2 h,
      potentially explaining a reduced effectiveness of hyperthermia for long time
      intervals. CONCLUSIONS: A short time interval between EBRT and hyperthermia is
      associated with a lower risk of in-field recurrence and a better overall
      survival. There was no evidence for difference in late toxicity.

PMID- 28449704
TI  - RapidPlan head and neck model: the objectives and possible clinical benefit.
AB  - BACKGROUND: To evaluate a knowledge based planning model for RapidPlan (RP)
      generated for advanced head and neck cancer (HNC) patient treatments, as well its
      ability to possibly improve the clinical plan quality. The stability of the model
      was assessed also for a different beam geometry, different dose fractionation and
      different management of bilateral structures (parotids). METHODS: Dosimetric and
      geometric data from plans of 83 patients presenting HNC were selected for the
      model training. All the plans used volumetric modulated arc therapy (VMAT,
      RapidArc) to treat two targets at dose levels of 69.96 and 54.45 Gy in 33
      fractions with simultaneous integrated boost. Two models were generated, the
      first separating the ipsi- and contra-lateral parotids, while the second
      associating the two parotids to a single structure for training. The optimization
      objectives were adjusted to the final model to better translate the institutional
      planning and dosimetric strategies and trade-offs. The models were validated on
      20 HNC patients, comparing the RP generated plans and the clinical plans. RP
      generated plans were also compared between the clinical beam arrangement and a
      simpler geometry, as well as for a different fractionation scheme. RESULTS: RP
      improved significantly the clinical plan quality, with a reduction of 2 Gy, 5 Gy,
      and 10 Gy of the mean parotid, oral cavity and laryngeal doses, respectively. A
      simpler beam geometry was deteriorating the plan quality, but in a small amount,
      keeping a significant improvement relative to the clinical plan. The two models,
      with one or two parotid structures, showed very similar results. NTCP evaluations
      indicated the possibility of improving (NTCP decreasing of about 7%) the toxicity
      profile when using the RP solution. CONCLUSIONS: The HNC RP model showed improved
      plan quality and planning stability for beam geometry and fractionation. An
      adequate choice of the objectives in the model is necessary for the trade-offs
      strategies.

PMID- 28449705
TI  - Large-scale detection of drug off-targets: hypotheses for drug repurposing and
      understanding side-effects.
AB  - BACKGROUND: Promiscuity in molecular interactions between small-molecules,
      including drugs, and proteins is widespread. Such unintended interactions can be
      exploited to suggest drug repurposing possibilities as well as to identify
      potential molecular mechanisms responsible for observed side-effects. METHODS: We
      perform a large-scale analysis to detect binding-site molecular interaction field
      similarities between the binding-sites of the primary target of 400 drugs against
      a dataset of 14082 cavities within 7895 different proteins representing a non
      redundant dataset of all proteins with known structure. Statistically-significant
      cases with high levels of similarities represent potential cases where the drugs
      that bind the original target may in principle bind the suggested off-target.
      Such cases are further analysed with docking simulations to verify if indeed the
      drug could, in principle, bind the off-target. Diverse sources of data are
      integrated to associated potential cross-reactivity targets with side-effects.
      RESULTS: We observe that promiscuous binding-sites tend to display higher levels
      of hydrophobic and aromatic similarities. Focusing on the most statistically
      significant similarities (Z-score >= 3.0) and corroborating docking results (RMSD
      < 2.0 A), we find 2923 cases involving 140 unique drugs and 1216 unique potential
      cross-reactivity protein targets. We highlight a few cases with a potential for
      drug repurposing (acetazolamide as a chorismate pyruvate lyase inhibitor,
      raloxifene as a bacterial quorum sensing inhibitor) as well as to explain the
      side-effects of zanamivir and captopril. A web-interface permits to explore the
      detected similarities for each of the 400 binding-sites of the primary drug
      targets and visualise them for the most statistically significant cases.
      CONCLUSIONS: The detection of molecular interaction field similarities provide
      the opportunity to suggest drug repurposing opportunities as well as to identify
      potential molecular mechanisms responsible for side-effects. All methods utilized
      are freely available and can be readily applied to new query binding-sites. All
      data is freely available and represents an invaluable source to identify further
      candidates for repurposing and suggest potential mechanisms responsible for side
      effects.

PMID- 28449706
TI  - Chemical and pathogen-induced inflammation disrupt the murine intestinal
      microbiome.
AB  - BACKGROUND: Salmonella is one of the most significant food-borne pathogens to
      affect humans and agriculture. While it is well documented that Salmonella
      infection triggers host inflammation, the impacts on the gut environment are
      largely unknown. A CBA/J mouse model was used to evaluate intestinal responses to
      Salmonella-induced inflammation. In parallel, we evaluated chemically induced
      inflammation by dextran sodium sulfate (DSS) and a non-inflammation control. We
      profiled gut microbial diversity by sequencing 16S ribosomal ribonucleic acid
      (rRNA) genes from fecal and cecal samples. These data were correlated to the
      inflammation marker lipocalin-2 and short-chain fatty acid concentrations.
      RESULTS: We demonstrated that inflammation, chemically or biologically induced,
      restructures the chemical and microbial environment of the gut over a 16-day
      period. We observed that the ten mice within the Salmonella treatment group had a
      variable Salmonella relative abundance, with three high responding mice dominated
      by >46% Salmonella at later time points and the remaining seven mice denoted as
      low responders. These low- and high-responding Salmonella groups, along with the
      chemical DSS treatment, established an inflammation gradient with chemical and
      low levels of Salmonella having at least 3 log-fold lower lipocalin-2
      concentration than the high-responding Salmonella mice. Total short-chain fatty
      acid and individual butyrate concentrations each negatively correlated with
      inflammation levels. Microbial communities were also structured along this
      inflammation gradient. Low levels of inflammation, regardless of chemical or
      biological induction, enriched for Akkermansia spp. in the Verrucomicrobiaceae
      and members of the Bacteroidetes family S24-7. Relative to the control or low
      inflammation groups, high levels of Salmonella drastically decreased the overall
      microbial diversity, specifically driven by the reduction of Alistipes and
      Lachnospiraceae in the Bacteroidetes and Firmicutes phyla, respectively.
      Conversely, members of the Enterobacteriaceae and Lactobacillus were positively
      correlated to high levels of Salmonella-induced inflammation. CONCLUSIONS: Our
      results show that enteropathogenic infection and intestinal inflammation are
      interrelated factors modulating gut homeostasis. These findings may prove
      informative with regard to prophylactic or therapeutic strategies to prevent
      disruption of microbial communities, or promote their restoration.

PMID- 28449708
TI  - The dose-response relationship for cardiovascular disease is not necessarily
      linear.
AB  - The probability for a complication after radiotherapy is usually a function of
      dose and volume in the organ or tissue of interest. In most epidemiological
      studies the risk for a complication is stratified in terms of dose, but not
      irradiated volume. We show that the obtained risk cannot generally be applied to
      radiotherapy patients.The epidemiological data of Darby et al. (N Engl J Med
      368:2527, 2013) who found a linear relationship between the excess relative risk
      of major coronary events as function of mean heart dose in patients treated with
      tangential breast irradiation are analyzed. We have used the relative seriality
      model for a partly irradiated heart ("a lot to a little") which models radiation
      therapy using two tangential fields. The relative seriality model was then used
      to predict NTCP of cardiovascular disease for a homogenously irradiated heart ("a
      little to a lot"). The relative seriality model was fitted to the data of Darby
      et al. (N Engl J Med 368:2527, 2013) for tangential breast irradiation. For the
      situation "a little to a lot" it was found that the dose-response relationship is
      sigmoidal and contradicts the findings of Darby et al. (N Engl J Med 368:2527,
      2013). It was shown in this work that epidemiological studies which predict a
      linear dose-response relationship for cardiovascular disease can be reproduced by
      bio-physical models for normal tissue complication. For irradiation situations
      which were not included in the epidemiological studies, e.g. a homogenous
      irradiation of the heart ("a little to a lot") the dose-response curve can be
      different. This could have consequences whether or not IMRT should be used for
      treating breast cancer. We believe that the results of epidemiological studies
      should not be generally used to predict normal tissue complications. It is better
      to use such data to optimize bio-physical models which can then be applied (with
      caution) to general treatment situations.

PMID- 28449709
TI  - Case Method in COPD education for primary care physicians: study protocol for a
      cluster randomised controlled trial.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common cause of
      morbidity and mortality worldwide. It is often undiagnosed and insufficiently
      managed. Effective forms of continuing medical education (CME) for primary care
      physicians (PCPs) are necessary to ensure the implementation of guidelines in
      clinical practice and, thus, improve patients' health. METHODS: In this study, we
      will measure the effects of CME by Case Method and compare them against those of
      traditional lectures and no CME at all through an unblinded, cluster randomised
      controlled trial (CRCT). Thirty-three primary health care centres (PHCCs) in
      Stockholm, Sweden, with a total of 180 PCPs will be involved. Twenty-two primary
      PHCCs, will be cluster-randomised into: an intervention group who will receive
      CME by Case Method (n = 11) and a control group who will receive traditional
      lectures (n = 11). The remaining PHCCs (n = 11) will be a reference group and
      will receive no CME. From the intervention and control groups, 460 randomly
      selected patients with COPD in GOLD stages 2 and 3 will participate, while no
      patients will be recruited from the reference group. For the patients, smoking
      status, actual treatment and urgent visits to a health provider due to airway
      problems will be registered. For the PCPs, professional competence (i.e.
      knowledge and management skills) in COPD, will be measured using a questionnaire
      based on current guidelines and guideline implementation problems in clinical
      practice which has previously been described by the authors. Data will be
      collected at baseline and at follow-up, which will be after 1.5 years for the
      patients, and 1 year for the PCPs. Statistical methods for individual-level and
      cluster-level analyses will be used. DISCUSSION: COPD is considered a
      particularly complex clinical challenge involving managing multimorbidity,
      symptom adaptation, and lifestyle problematisation. Case Method in CME for PCPs
      may contribute to a better understanding of the impact of COPD on patients' lives
      and, thus, improve their management of it. The present study is expected to
      contribute scientific knowledge about indicators for an effective CME in COPD
      that is tailor-made to primary care physicians. TRIAL REGISTRATION:
      ClinicalTrials.gov, identifier: NCT02213809 . Registered on 10 August 2014.
      Protocol version: Issue date: May 2014.

PMID- 28449707
TI  - Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic
      Creutzfeldt-Jakob disease.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human
      prion disease and it is characterized by the presence of neuronal loss,
      spongiform degeneration, chronic inflammation and the accumulation of misfolded
      and pathogenic prion protein (PrPSc). The molecular mechanisms underlying these
      alterations are largely unknown, but the presence of intracellular neuronal
      calcium (Ca2+) overload, a general feature in models of prion diseases, is
      suggested to play a key role in prion pathogenesis.Here we describe the presence
      of massive regulation of Ca2+ responsive genes in sCJD brain tissue, accompanied
      by two Ca2+-dependent processes: endoplasmic reticulum stress and the activation
      of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in
      sCJD is linked to the cleavage of their cellular substrates, impaired autophagy
      and lysosomal damage, which is partially reversed by Calpain inhibition in a
      cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity
      of PrPSc in a prion conversion assay. Neuronal lysosomal impairment caused by
      Calpain over activation leads to the release of the lysosomal protease Cathepsin
      S that in sCJD mainly localises in axons, although massive Cathepsin S
      overexpression is detected in microglial cells. Alterations in Ca2+ homeostasis
      and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of
      the disease as detected in a humanized sCJD mouse model.Altogether our work
      indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor
      to the pathogenesis of sCJD at multiple molecular levels and a potential target
      for therapeutic intervention.

PMID- 28449710
TI  - Effects of colloid pre-loading on thromboelastography during elective
      intracranial tumor surgery in pediatric patients: hydroxyethyl starch 130/0.4
      versus 5% human albumin.
AB  - BACKGROUND: Volume replacement therapy with colloid is still worth studying in
      major pediatric surgery with potential risk of bleeding. This study assessed the
      effects of 6% hydroxyethyl starch (HES) 130/0.4 and 5% Human Albumin (HA) on
      coagulation tested by thromboelastography (TEG) during elective intracranial
      tumor surgery in pediatric patients. METHODS: In this randomized controlled
      trial, 60 patients undergoing intracranial tumor resection under general
      anesthesia were assigned to HES and HA groups (n = 30), and administered preloads
      of 20 mL . kg-1 HES 130/0.4 and 5% HA, respectively, prior to dura opening.
      Primary outcomes were perioperative thromboelastography findings, and hemodynamic
      and hematological parameters. Blood transfusion, perioperative fluid balance,
      intracranial pressure, mortality, intensive care unit stay, and hospital stay
      were also assessed. RESULTS: TEG parameters did not differ after preloading
      compared to baseline values in either group, except for a decrease in maximum
      amplitude immediately after infusion (HES group, 57.6 +/- 6.0 mm vs. 50.9 +/- 9.2
      mm; HA group, 60.1 +/- 7.9 mm vs. 56.6 +/- 7.1 mm; p < 0.01), which was restored
      to preoperative levels 1 h after fluid infusion. Total perioperative fluid
      balance, blood loss or transfusion, intracranial pressure, and hematological and
      hemodynamic variables were similar between both groups (p > 0.05). Mortality,
      length of hospital stay, and clinical complications were similar between both
      groups. CONCLUSION: These findings suggest that HES and HA might have no
      significant differences regarding coagulation as assessed by TEG during pediatric
      intracranial tumor surgery with 20 ml/kg volume pre-loading, which can maintain
      stable hemodynamics and may represent a new avenue for volume therapy during
      brain tumor resection in pediatrics. TRIAL REGISTRATION: ChiCTR-IPR- 16009333 ,
      retrospectively registered October 8, 2016.

PMID- 28449711
TI  - Human mesenchymal stem cells maintain their phenotype, multipotentiality, and
      genetic stability when cultured using a defined xeno-free human plasma fraction.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) show promising characteristics for
      their use in advanced therapy medicinal products. However, there are some
      unresolved concerns, such as the use of animal components for their expansion. In
      this study we assessed the suitability of a xeno-free supplement for cell culture
      (SCC) derived from human plasma, to culture and expand human MSCs (hMSCs) from
      different origins. Characteristics of viable cultured hMSCs such as genetic
      stability, phenotype and multipotentiality were qualitatively evaluated. METHODS:
      hMSCs from adipose tissue (AT), bone marrow (BM) and umbilical cord (UC) and
      supplier sources (commercial/non-commercial) were used. After hMSCs expansion in
      a xeno-free medium, classical hMSCs markers were studied by immunocytochemistry,
      and genetic stability was tested by classic karyotyping. The capacity of hMSCs to
      differentiate into adipogenic, osteogenic, and chondrogenic cells in
      differentiation media was assessed using different staining. Different lots of
      SCC were used to assure consistency between batches. RESULTS: All hMSCs tested
      maintained their morphology and adherence to plastic during their expansion, and
      preserved their genetic stability, phenotype and differentiation potential. No
      differences were observed when using different lots of SCC. Moreover, the
      proliferation rate, evaluated as population doubling time (PDT) of commercial BM
      and AT hMSCs, was higher in the xeno-free medium than in the control media
      provided by the suppliers of the cells (PDT of 4.6 for BM-hMSC and 6.4 for AT
      hMSC in xeno-free medium, and 7.0 and 14.7 respectively in the commercial media).
      UC-hMSCs PDT was similar in all the media tested. When using non-commercial BM
      hMSCs, PDT was lower in the xeno-free medium, but reverted to the control level
      with the addition of growth factors. CONCLUSIONS: SCC-containing medium can be a
      feasible xeno-free alternative to expand hMSCs for advanced therapies.

PMID- 28449712
TI  - Barriers and facilitators to enrollment and re-enrollment into the community
      health funds/Tiba Kwa Kadi (CHF/TIKA) in Tanzania: a cross-sectional inquiry on
      the effects of socio-demographic factors and social marketing strategies.
AB  - BACKGROUND: Introduction of a health insurance scheme is one of the ways to
      enhance access to health care services and to protect individuals from
      catastrophic health expenditures. Little is known on the influence of socio
      demographic and social marketing strategies on enrollment and re-enrollment in
      the Community Health Fund/Tiba Kwa Kadi (CHF/TIKA) in Tanzania. METHODS: This
      cross-sectional study employed quantitative methods for data collection between
      November 2014 and March 2015 in Singida and Shinyanga regions. Relationship
      between variables was obtained through Chi-square test and multivariate logistic
      regression. RESULTS: We recruited 496 participants in the study. Majority (92.7%)
      of participants consented to participate, with 229 (49.8%) and 231 (50.2%)
      members and non members of CHF/TIKA respectively. Majority (90.9%) were aware of
      CHF/TIKA. Majority of CHF/TIKA members and non-members (90% and 68.3%
      respectively) reported health facility-based sensitization as the most common
      social marketing approach employed to market the CHF/TIKA. The most popular
      marketing strategies in the country including traditional dances, football games,
      radio, television, news papers, and mosques/church were reported by few CHF and
      non CHF members. Multivariate Logistic regression models revealed no significant
      association between social marketing strategies and enrollment, but only socio
      demographics; including marital status (AOR = 2.0, 95% CI 1.1-3.8) and family
      size (household with >= 6 members) (AOR = 1.5, 95% CI 1.0-2.5), were significant
      factors associated with enrollment/re-enrollment rate. CONCLUSIONS: This study
      indicated that low level of utilization of available social marketing strategies
      and socio-demographic factors are the barriers for attracting members to join the
      schemes. There is a need for applying various social marketing strategies and
      considering different facilitating and impending socio-demographic factors for
      the growth and sustainability of the scheme as we move towards universal health
      coverage.

PMID- 28449713
TI  - Dosimetric comparison of helical tomotherapy, VMAT, fixed-field IMRT and 3D
      conformal radiotherapy for stage I-II nasal natural killer T-cell lymphoma.
AB  - BACKGROUND: The aim of this study was to compare radiotherapy plans for Stage I
      II nasal natural killer/T-cell lymphoma (NNKTL) using helical tomotherapy (HT),
      volumetric-modulated arc therapy (VMAT), Fixed-Field intensity-modulated
      radiotherapy (IMRT), and three-dimensional conformal radiotherapy (3D-CRT).
      METHODS: Eight patents with Stage I-II NNKTL treated with IMRT were re-planned
      for HT, VMAT (two full arcs), and 3D-CRT. The quality of target coverage, the
      exposure of normal tissue and the efficiency of radiation delivery were analyzed.
      RESULTS: HT showed significant improvement over IMRT in terms of D98%, cold spot
      volume and homogeneity index (HI) of planning target volume (PTV). VMAT provided
      best dose uniformity (p = 0.000) to PTV, while HT had best dose homogeneity among
      the four radiotherapy techniques (p = 0.000) to PTV. VMAT obviously reduced
      treatment time (p = 0.010; 0.000) compared to HT and IMRT. Mean dose of left and
      right optic nerve was significantly reduced by IMRT compared to HT (19.86%, p =
      0.000; 21.40%, p = 0.002) and VMAT (8.97%, p = 0.002; 9.35%, p = 0.001), and
      maximum dose of left lens of VMAT increased over the HT (36.25%, p = 0.043) and
      IMRT (40.65%, p = 0.001). CONCLUSION: The unexpected results show that both HT
      and VMAT can achieve higher conformal treatment plans while getting worse organs
      at risk (OARs) sparing than IMRT for patients with Stage I-II NNKTL. VMAT
      requires the shortest delivery time, and IMRT delivers the lowest dose to most
      OARs. The results could provide guidance for selecting proper radiation
      technologies for different cases.

PMID- 28449714
TI  - Detecting central fixation by means of artificial neural networks in a pediatric
      vision screener using retinal birefringence scanning.
AB  - BACKGROUND: Reliable detection of central fixation and eye alignment is essential
      in the diagnosis of amblyopia ("lazy eye"), which can lead to blindness. Our lab
      has developed and reported earlier a pediatric vision screener that performs
      scanning of the retina around the fovea and analyzes changes in the polarization
      state of light as the scan progresses. Depending on the direction of gaze and the
      instrument design, the screener produces several signal frequencies that can be
      utilized in the detection of central fixation. The objective of this study was to
      compare artificial neural networks with classical statistical methods, with
      respect to their ability to detect central fixation reliably. METHODS: A
      classical feedforward, pattern recognition, two-layer neural network architecture
      was used, consisting of one hidden layer and one output layer. The network has
      four inputs, representing normalized spectral powers at four signal frequencies
      generated during retinal birefringence scanning. The hidden layer contains four
      neurons. The output suggests presence or absence of central fixation.
      Backpropagation was used to train the network, using the gradient descent
      algorithm and the cross-entropy error as the performance function. The network
      was trained, validated and tested on a set of controlled calibration data
      obtained from 600 measurements from ten eyes in a previous study, and was
      additionally tested on a clinical set of 78 eyes, independently diagnosed by an
      ophthalmologist. RESULTS: In the first part of this study, a neural network was
      designed around the calibration set. With a proper architecture and training, the
      network provided performance that was comparable to classical statistical
      methods, allowing perfect separation between the central and paracentral fixation
      data, with both the sensitivity and the specificity of the instrument being 100%.
      In the second part of the study, the neural network was applied to the clinical
      data. It allowed reliable separation between normal subjects and affected
      subjects, its accuracy again matching that of the statistical methods.
      CONCLUSION: With a proper choice of a neural network architecture and a good,
      uncontaminated training data set, the artificial neural network can be an
      efficient classification tool for detecting central fixation based on retinal
      birefringence scanning.

PMID- 28449715
TI  - Functional implications of microbial and viral gut metagenome changes in early
      stage L-DOPA-naive Parkinson's disease patients.
AB  - BACKGROUND: Parkinson's disease (PD) presently is conceptualized as a protein
      aggregation disease in which pathology involves both the enteric and the central
      nervous system, possibly spreading from one to another via the vagus nerves. As
      gastrointestinal dysfunction often precedes or parallels motor symptoms, the
      enteric system with its vast diversity of microorganisms may be involved in PD
      pathogenesis. Alterations in the enteric microbial taxonomic level of L-DOPA
      naive PD patients might also serve as a biomarker. METHODS: We performed
      metagenomic shotgun analyses and compared the fecal microbiomes of 31 early
      stage, L-DOPA-naive PD patients to 28 age-matched controls. RESULTS: We found
      increased Verrucomicrobiaceae (Akkermansia muciniphila) and unclassified
      Firmicutes, whereas Prevotellaceae (Prevotella copri) and Erysipelotrichaceae
      (Eubacterium biforme) were markedly lowered in PD samples. The observed
      differences could reliably separate PD from control with a ROC-AUC of 0.84.
      Functional analyses of the metagenomes revealed differences in microbiota
      metabolism in PD involving the ?-glucuronate and tryptophan metabolism. While the
      abundances of prophages and plasmids did not differ between PD and controls,
      total virus abundance was decreased in PD participants. Based on our analyses,
      the intake of either a MAO inhibitor, amantadine, or a dopamine agonist (which in
      summary relates to 90% of PD patients) had no overall influence on taxa abundance
      or microbial functions. CONCLUSIONS: Our data revealed differences of colonic
      microbiota and of microbiota metabolism between PD patients and controls at an
      unprecedented detail not achievable through 16S sequencing. The findings point to
      a yet unappreciated aspect of PD, possibly involving the intestinal barrier
      function and immune function in PD patients. The influence of the parkinsonian
      medication should be further investigated in the future in larger cohorts.

PMID- 28449716
TI  - The role of informal dimensions of safety in high-volume organisational routines:
      an ethnographic study of test results handling in UK general practice.
AB  - BACKGROUND: The handling of laboratory, imaging and other test results in UK
      general practice is a high-volume organisational routine that is both complex and
      high risk. Previous research in this area has focused on errors and harm, but a
      complementary approach is to better understand how safety is achieved in everyday
      practice. This paper ethnographically examines the role of informal dimensions of
      test results handling routines in the achievement of safety in UK general
      practice and how these findings can best be developed for wider application by
      policymakers and practitioners. METHODS: Non-participant observation was
      conducted of high-volume organisational routines across eight UK general
      practices with diverse organisational characteristics. Sixty-two semi-structured
      interviews were also conducted with the key practice staff alongside the analysis
      of relevant documents. RESULTS: While formal results handling routines were
      described similarly across the eight study practices, the everyday structure of
      how the routine should be enacted in practice was informally understood. Results
      handling safety took a range of local forms depending on how different aspects of
      safety were prioritised, with practices varying in terms of how they balanced
      thoroughness (i.e. ensuring the high-quality management of results by the most
      appropriate clinician) and efficiency (i.e. timely management of results)
      depending on a range of factors (e.g. practice history, team composition). Each
      approach adopted created its own potential risks, with demands for thoroughness
      reducing productivity and demands for efficiency reducing handling quality.
      Irrespective of the practice-level approach adopted, staff also regularly varied
      what they did for individual patients depending on the specific context (e.g.
      type of result, patient circumstances). CONCLUSIONS: General practices variably
      prioritised a legitimate range of results handling safety processes and outcomes,
      each with differing strengths and trade-offs. Future safety improvement
      interventions should focus on how to maximise practice-level knowledge and
      understanding of the range of context-specific approaches available and the
      safeties and risks inherent in each within the context of wider complex system
      conditions and interactions. This in turn has the potential to inform new kinds
      of proactive, contextually appropriate approaches to intervention development and
      implementation focusing on the enhanced deliberation of the safety of existing
      high-volume routines.

PMID- 28449717
TI  - A review of patient-reported outcome measures to assess female infertility
      related quality of life.
AB  - BACKGROUND: Infertility has a negative impact on quality of life (QoL) and well
      being of affected individuals and couples. A variety of patient-reported outcome
      (PRO) measures to assess infertility-related QoL are available; however, there is
      a concern regarding potential issues with their development methodology,
      validation and use. This review aimed to i) identify PRO measures used in
      infertility interventional studies ii) assess validation evidence to identify a
      reliable, valid PRO measure to assess changes in QoL or treatment satisfaction in
      clinical studies with female patients following treatment with novel therapies
      iii) identify potential gaps in evidence for validity. METHODS: A structured
      literature search of Medline, Embase, and the Cochrane Library (accessed in
      September 2015) was conducted using pre-defined search terms. The identified
      publications were reviewed applying eligibility criteria to select interventional
      female infertility studies using PROs. Infertility-specific PRO measures
      assessing QoL, treatment satisfaction or psychiatric health, and included in
      studies by >=2 research groups were selected and critically reviewed in light of
      scientific and regulatory guidance (e.g. FDA PRO Guidance for Industry) for
      evidence of content validity, psychometric strength, and patient acceptability.
      RESULTS: The literature search and hand-searching yielded 122 publications; 78
      unique PRO measures assessing QoL, treatment satisfaction or psychiatric health
      were identified. Five PRO measures met the selection criteria for detailed
      review: Fertility Quality of Life (FertiQoL); Fertility Problem Inventory (FPI);
      Fertility Problem Stress (FPS); Infertility Questionnaire (IFQ); Illness
      Cognitions Questionnaire adapted for Infertility (ICQ-I). None of the PRO
      measures met all validation criteria. The FertiQoL was the most widely used
      infertility-specific PRO measure to assess QoL in interventional studies, with
      reasonable evidence for adequate content validity, psychometric strength, and
      linguistic validation. However, gaps in evidence remain including test-retest
      reliability and thresholds for interpreting clinically important changes. While
      the FPI demonstrated reasonable evidence for content and psychometric validity,
      its utility as an outcome measure is limited by a lack of recall period.
      CONCLUSION: The FertiQoL and the FPI are potentially useful measures of
      infertility-related QoL in interventional studies. Further research is
      recommended to address gaps in evidence and confirm both PRO measures as reliable
      assessments of patient outcomes.

PMID- 28449718
TI  - HIF-1alpha promoted vasculogenic mimicry formation in hepatocellular carcinoma
      through LOXL2 up-regulation in hypoxic tumor microenvironment.
AB  - BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma (HCC)
      have steadily increased in recent years. A hypoxic microenvironment is one of the
      most important characteristics of solid tumors which has been shown to promote
      tumor metastasis, epithelial-mesenchymal transition and angiogenesis. Epithelial
      mesenchymal transition and vasculogenic mimicry have been regarded as crucial
      contributing factors to cancer progression. HIF-1alpha functions as a master
      transcriptional regulator in the adaptive response to hypoxia. Lysyl oxidases
      like 2 (LOXL2) is a member of the lysyl oxidase family, which main function is to
      catalyze the covalent cross-linkages of collagen and elastin in the extracellular
      matrix. Recent work has demonstrated that HIF-1alpha promotes the expression of
      LOXL2, which is believed to amplify tumor aggressiveness. LOXL2 has shown to
      promote metastasis and is correlated with poor prognosis in hepatocellular
      carcinoma. The purpose of our study is to explore the role of HIF-1alpha in
      progression and metastasis of hepatocellular carcinoma by promoting the
      expression of LOXL2 as well as the potential regulatory mechanism. METHODS: HIF
      1alpha, LOXL2 expression and CD31/periodic acid-Schiff double staining in HCC
      patient samples were examined by immunohistochemical staining. shRNA plasmids
      against HIF-1alpha was used to determine whether LOXL2 been increased by HIF
      1alpha. We monitored a series of rescue assays to demonstrate our hypothesis that
      LOXL2 is required and sufficient for HIF-1alpha induced EMT and VM formation,
      which mediates cellular transformation and takes effect in cellular invasion.
      Then we performed GeneChip(r) Human Transcriptome Array (HTA) 2.0 in HepG2 cells,
      HepG2 cells overexpressed LOXL2 and HepG2 cells treated with CoCl2. RESULTS: In
      clinical HCC tissues, it confirmed a positive relationship between HIF-1alpha and
      LOXL2 protein. Importantly, HIF-1alpha and LOXL2 high expression and the presence
      of vasculogenic mimicry were correlated to poor prognosis. HIF-1alpha was found
      to induce EMT, HCC cell migration, invasion and VM formation by regulating LOXL2.
      The results of microarray assays were analyzed. CONCLUSION: HIF-1alpha plays an
      important role in the development of HCC by promoting HCC metastasis, EMT and VM
      through up-regulating LOXL2. This study highlights the potential therapeutic
      value of targeting LOXL2 for suppression of HCC metastasis and progression.

PMID- 28449719
TI  - Interference of retroviral envelope with vaccine-induced CD8+ T cell responses is
      relieved by co-administration of cytokine-encoding vectors.
AB  - BACKGROUND: Retroviral envelope (Env) proteins are known to exhibit
      immunosuppressive properties, which become apparent not only in retroviral
      infections, but also in gene-based immunizations using retroviral immunogens,
      where envelope interferes with the induction of CD8+ T cell responses towards
      another, simultaneously or subsequently delivered, immunogen. RESULTS: In the
      Friend retrovirus mouse model, immunization with a plasmid encoding the Friend
      murine leukemia virus (F-MuLV) Leader-Gag protein resulted in induction of a
      strong GagL85-93-specific CD8+ T cell response, while the response was completely
      abrogated by co-immunization with an F-MuLV Env-encoding plasmid. In order to
      overcome this interference of retroviral envelope, we employed plasmids encoding
      the cytokines interleukin (IL) 1beta, IL2, IL12, IL15, IL21, IL28A or granulocyte
      macrophage colony-stimulating factor (GM-CSF) as genetic adjuvants. Co
      application of plasmids encoding IL2, IL12, IL21, IL28A and especially GM-CSF
      rescued the induction of GagL85-93-specific CD8+ T cells in mice vaccinated with
      FV Leader-Gag and Env. Mice that were immunized with plasmids encoding Leader-Gag
      and Env and the cytokines IL1beta, IL12, IL15, IL28A or GM-CSF, but not Leader
      Gag and Env without any cytokine, showed significantly reduced viral loads upon a
      high-dose Friend virus challenge infection. CONCLUSIONS: Our data demonstrate the
      potency of cytokine-encoding vectors as adjuvants and immune modulators in
      composite vaccines for anti-retroviral immunization.

PMID- 28449720
TI  - Evolution of blood pressure in children with congenital and acquired solitary
      functioning kidney.
AB  - BACKGROUND: It is not yet clear if blood pressure and renal function changes
      evolve differently in children with a congenital or acquired solitary functioning
      kidney. This study aims to assess if there are any differences between these two
      types of solitary kidney patients. METHODS: Current research is a retrospective
      study assessing the evolution of glomerular filtration rate, proteinuria, and
      blood pressure in clinical records of 55 children with a solitary functioning
      kidney (37 congenital and 18 acquired). We used the medical records of children
      who had been assisted, in our unit of pediatric nephrology, for a period of 14
      years (168 months), from the time of diagnosis, between January/1997 and
      December/2015. RESULTS: During the study period, glomerular filtration rate (T0
      128.89 +/- 32.24 vs T14 118.51 +/- 34.45 ml/min/1.73 m2, p NS) and proteinuria
      (T0 85.14 +/- 83.13 vs T14 159.03 +/- 234.66 mg/m2/die, p NS) demonstrated no
      significant change. However, after 14 years of follow-up 76.4% of patients had
      increased levels of arterial hypertension with values over the 90th percentile
      for gender, age, and height. Specifically, children with an acquired solitary
      functioning kidney mainly developed hypertension [T0 2/17 (12%) vs T14 9/17
      (52.9%) p < 0.025], whereas children with a congenital solitary functioning
      kidney mainly developed pre-hypertension [T0 3/38 (7.9%) vs T14 17/38 (44.7%) p <
      0.0005]. CONCLUSIONS: The renal function of children with solitary functioning
      kidneys remains stable during a follow-up of 14 years. However, these children
      should be carefully monitored for their tendency to develop arterial blood
      pressure greater than the 90th percentile for gender, age, and height.

PMID- 28449723
TI  - Determinants of modern contraceptive use among sexually active men in Kenya.
AB  - BACKGROUND: Research in Kenya has focussed on family planning from women's
      perspectives, with the aim of helping reduce the burden of unintended
      pregnancies. As such, the determinants of modern contraceptive use among sexually
      active women are well documented. However, the perspectives of men should be
      considered not only as women's partners, but also as individuals with distinct
      reproductive histories and desires of their own. This study seeks to understand
      the determinants of modern contraceptive use among sexually active men, by
      exploring factors that are correlated with modern contraceptive use. METHODS: The
      data source is the nationally representative 2014 Kenya Demographic and Health
      Survey (DHS) of men aged 15-54 years. The analysis is restricted to 9,514 men who
      reported being sexually active in the past 12 months prior to the survey, as they
      were likely to report either doing something or not to avoid or delay pregnancy.
      We use bivariate and multinomial logistic regression to assess factors that
      influence modern contraceptive use among sexually active men. RESULTS: Findings
      from the bivariate and multinomial logistic regression indicate that region of
      residence, marital status, religion, wealth, interaction with a health care
      provider, fertility preference, number of sexual partners and access to media
      were all significantly associated with modern contraceptive use among sexually
      active men. CONCLUSION: Provider-client interaction as well as dissemination of
      information through mass media has the potential to increase knowledge and uptake
      of modern contraceptives. Similar efforts targeting segments of the population
      where contraceptive uptake is low are recommended.

PMID- 28449721
TI  - Effectiveness of an intervention for improving drug prescription in primary care
      patients with multimorbidity and polypharmacy: study protocol of a cluster
      randomized clinical trial (Multi-PAP project).
AB  - BACKGROUND: Multimorbidity is associated with negative effects both on people's
      health and on healthcare systems. A key problem linked to multimorbidity is
      polypharmacy, which in turn is associated with increased risk of partly
      preventable adverse effects, including mortality. The Ariadne principles describe
      a model of care based on a thorough assessment of diseases, treatments (and
      potential interactions), clinical status, context and preferences of patients
      with multimorbidity, with the aim of prioritizing and sharing realistic treatment
      goals that guide an individualized management. The aim of this study is to
      evaluate the effectiveness of a complex intervention that implements the Ariadne
      principles in a population of young-old patients with multimorbidity and
      polypharmacy. The intervention seeks to improve the appropriateness of
      prescribing in primary care (PC), as measured by the medication appropriateness
      index (MAI) score at 6 and 12 months, as compared with usual care.
      METHODS/DESIGN: Design: pragmatic cluster randomized clinical trial. Unit of
      randomization: family physician (FP). Unit of analysis: patient. SCOPE: PC health
      centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain).
      POPULATION: patients aged 65-74 years with multimorbidity (>=3 chronic diseases)
      and polypharmacy (>=5 drugs prescribed in >=3 months). SAMPLE SIZE: n = 400 (200
      per study arm). INTERVENTION: complex intervention based on the implementation of
      the Ariadne principles with two components: (1) FP training and (2) FP-patient
      interview. OUTCOMES: MAI score, health services use, quality of life (Euroqol 5D
      5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett),
      and clinical and socio-demographic variables. STATISTICAL ANALYSIS: primary
      outcome is the difference in MAI score between T0 and T1 and corresponding 95%
      confidence interval. Adjustment for confounding factors will be performed by
      multilevel analysis. All analyses will be carried out in accordance with the
      intention-to-treat principle. DISCUSSION: It is essential to provide evidence
      concerning interventions on PC patients with polypharmacy and multimorbidity,
      conducted in the context of routine clinical practice, and involving young-old
      patients with significant potential for preventing negative health outcomes.
      TRIAL REGISTRATION: Clinicaltrials.gov, NCT02866799.

PMID- 28449724
TI  - Does medical school research productivity predict a resident's research
      productivity during residency?
AB  - BACKGROUND: Research productivity is an important component of the CanMEDS
      Scholar role and is an accreditation requirement of Canadian Otolaryngology
      training programs. Our objective was to determine if an association exists
      between publication rates before and during Otolaryngology residency. METHODS: We
      obtained the names for all certified Canadian Otolaryngologists who graduated
      between 1998 and 2013 inclusive, and conducted a Medline search for all of their
      publications. Otolaryngologists were subgrouped based on year of residency
      graduation and the number of articles published pre-residency and during
      residency (0 or >=1). Chi-squared analyses were used to evaluate whether
      publications pre-residency and year of graduation were associated with
      publications during residency. RESULTS: We obtained data for 312 Canadian
      Otolaryngologists. Of those 312 graduates, 46 (14.7%) had no identifiable
      publications on PubMed and were excluded from the final data analysis.
      Otolaryngology residents had a mean 0.65 (95% CI 0.50-0.80) publications before
      residency and 3.35 (95% CI 2.90-3.80) publications during residency. Between 1998
      and 2013, mean publication rates before and during residency both increased
      significantly (R 2 = 0.594 and R 2 = 0.759, respectively), whereas publication
      rates after residency graduation has stagnated (R 2 = 0.023). The odds of
      publishing during residency was 5.85 times higher (95% CI 2.69-12.71) if a
      resident published prior to residency (p < 0.0001). The Spearman correlation
      coefficient between publications before and during residency is 0.472 (p <
      0.0001). CONCLUSION: Residents who publish at least one paper before residency
      are nearly six times as likely to publish during residency than those who did not
      publish before residency. These findings may help guide Otolaryngology program
      selection committees in ranking the best CaRMS candidates.

PMID- 28449722
TI  - Prevalence of tick-borne haemoparasites in small ruminants in Turkey and
      diagnostic sensitivity of single-PCR and RLB.
AB  - BACKGROUND: Tick-borne haemoparasitic diseases (TBHDs), caused by Theileria,
      Babesia, Anaplasma and Ehrlichia, are common in regions of the world where the
      distributions of host, pathogen and vector overlap. Many of these diseases
      threaten livestock production and some also represent a concern to human public
      health. The primary aim of this study was to determine the prevalence of the
      above-mentioned pathogens in a large number of blood samples (n = 1979) collected
      from sheep (n = 1727) and goats (n = 252) in Turkey. A secondary aim was to
      assess the diagnostic sensitivity of a number of species-specific polymerase
      chain reaction (PCR) tests and the reverse line blotting (RLB) assay. DNA samples
      were screened using species-specific PCR for the presence of Theileria ovis,
      Theileria sp. MK, T. lestoquardi, T. uilenbergi, T. luwenshuni, Babesia ovis,
      Anaplasma ovis and A. phagocytophilum while RLB was undertaken to test for the
      presence of all known Theileria, Babesia, Anaplasma and Ehrlichia species. The
      diagnostic sensitivity of these two approaches was then compared in terms of
      their ability to detect single species and mixed infections. RESULTS: Overall, 84
      and 74.43% of the small ruminants sampled were identified as hosting one or more
      pathogen(s) by species-specific PCR and RLB respectively. The presence of
      Theileria sp. OT1, T. luwenshuni and T. uilenbergi in Turkey was revealed for the
      first time while the presence of Babesia motasi, B. crassa and T. separata in
      Turkish small ruminants was confirmed using molecular methods. A high prevalence
      of mixed infection was evident, with PCR and RLB approaches indicating that 52.24
      and 35.42% of animals were co-infected with multiple species, respectively. More
      than 80% of the mixed infections contained T. ovis and/or A. ovis. The RLB
      approach was found to be capable of detecting mixed infections with species such
      as Theileria sp. OT1, Theileria sp. OT3, T. separata, B. crassa and Babesia spp.
      CONCLUSION: The results indicated that pathogens causing TBHDs are highly
      prevalent in sheep and goats in Turkey. The diagnostic sensitivity of species
      specific single PCR was generally higher than that of RLB. However, the latter
      approach was still capable of identifying a high proportion of individuals
      containing mixed-species infections. The use of species-specific single PCR is
      recommended to accurately estimate pathogen prevalence and to identify co
      infected hosts.

PMID- 28449725
TI  - Maxillofacial prosthodontics practice profile: a survey of non-United States
      prosthodontists.
AB  - BACKGROUND: This study surveyed non-United States maxillofacial prosthodontists
      (MFP) to determine their practice profile and rationale for pursuing an MFP
      career. METHODS: Email addresses for the MFP were obtained from the International
      Society for Maxillofacial Rehabilitation, American Academy of Maxillofacial
      Prosthetics, and International Academy for Oral Facial Rehabilitation. Emails
      with a link to the electronic survey program were sent to each participant. Chi
      square and Mann-Whitney-U tests were used to investigate the influence of formal
      MFP training on professional activities and type of treatments provided. RESULTS:
      One hundred twelve respondents (response rate 39%) from 33 nationalities returned
      the survey. The top three reasons for pursuing an MFP career were personal
      satisfaction, prosthodontics residency exposure, and mentorship. The predominant
      employment setting was affiliation with a university (77%). There were
      significant differences between respondents with and without formal MFP training
      regarding provision of surgical treatments (P = 0.021) and dental oncology (P =
      0.017). Most treatments were done together with otolaryngology, oral surgery
      (68%) and head and neck surgery (61%). Practitioners not affiliated with a
      university spent significantly more time in clinical practice (P = 0.002),
      whereas respondents affiliated with universities spent significantly more time in
      teaching/training (P = 0.008) and funded research (P = 0.015). CONCLUSIONS:
      Personal satisfaction is the most important factor in a decision to choose an MFP
      career. Most of the MFPs work at a university and within a multidisciplinary
      setting. There were differences regarding type of treatments provided by
      respondents with and without formal MFP training.

PMID- 28449726
TI  - Low parental awareness about energy (calorie) recommendations for children's
      restaurant meals: findings from a national survey in the USA.
AB  - OBJECTIVE: To assess parental awareness of per-meal energy (calorie)
      recommendations for children's restaurant meals and to explore whether calorie
      awareness was associated with parental sociodemographic characteristics and
      frequency of eating restaurant food. DESIGN: Cross-sectional online survey
      administered in July 2014. Parents estimated calories (i.e. kilocalories; 1
      kcal=4.184 kJ) recommended for a child's lunch/dinner restaurant meal (range: 0
      2000 kcal). Responses were categorized as 'underestimate' (600 kcal). Confidence
      in response was measured on a 4-point scale from 'very unsure' to 'very sure'.
      Logistic regressions estimated the odds of an 'accurate' response and confident
      response ('somewhat' or 'very sure') by parental sociodemographic characteristics
      and frequency of eating from restaurants. Sampling weights based on demographics
      were incorporated in all analyses. SETTING: USA. SUBJECTS: Parents (n 1207) of 5
      12-year-old children. RESULTS: On average, parents estimated 631 (se 19.4) kcal
      as the appropriate amount for a 5-12-year-old child's meal. Thirty-five per cent
      answered in the accurate range, while 33.3 and 31.8 % underestimated and
      overestimated, respectively. Frequent dining at restaurants, lower income and
      urban geography were associated with lower odds of answering accurately. Parents'
      confidence in their estimates was low across the sample (26.0 % confident) and
      only 10.1 % were both accurate and confident. CONCLUSIONS: Parent education about
      calorie recommendations for children could improve understanding and use of menu
      labelling information in restaurants. Targeted strategies are recommended to
      ensure that such efforts address, rather than exacerbate, health disparities.

PMID- 28449728
TI  - Stayin' on Track: the feasibility of developing Internet and mobile phone-based
      resources to support young Aboriginal fathers.
AB  - Young Aboriginal fathers face social and emotional challenges in the transition
      to fatherhood, yet culturally appropriate support mechanisms are lacking. Peer
      mentoring to develop online- and mobile phone-based resources and support may be
      a viable approach to successfully engage these young men. This feasibility study
      engaged two trusted Aboriginal mentors and researchers to partner with one
      regional and two rural Aboriginal communities in New South Wales, Australia.
      Early in the research process, 20 young Aboriginal fathers were recruited as co
      investigators. These fathers were integral in the development of web-based
      resources and testing of mobile phone-based text messaging and mood-tracking
      programs tailored to provide fathering and mental health support. Overwhelmingly
      positive feedback from evaluations reinforced community pride in and ownership of
      the outcomes. The young men's involvement was instrumental in not only developing
      culturally appropriate support, but also in building their capacity as role
      models for other fathers in the community. The positive results from this
      feasibility study support the adoption of participatory approaches in the
      development of resources for Aboriginal communities.

PMID- 28449729
TI  - Emergence of new recombinant noroviruses GII.p16-GII.4 and GII.p16-GII.2, France,
      winter 2016 to 2017.
AB  - An early increase in outbreaks of norovirus gastroenteritis characterised at the
      French National Reference Centre occurred this winter season. They were
      concurrent with an unusual pattern of circulating strains, with three predominant
      genotypes: the re-emergent variant GII.P4 2009-GII.4 2012 found in 28% of
      norovirus outbreaks and two new emergent recombinant strains GII.P16-GII.4 2012
      and GII.P16-GII.2 never before observed in France, found in 24% and 14% of
      norovirus outbreaks, respectively.

PMID- 28449730
TI  - Hepatitis E and blood donation safety in selected European countries: a shift to
      screening?
AB  - The public health implications of hepatitis E virus (HEV) in Europe have changed
      due to increasing numbers of hepatitis E cases and recent reports of chronic,
      persistent HEV infections associated with progression to cirrhosis in
      immunosuppressed patients. The main infectious risk for such immunosuppressed
      patients is exposure to undercooked infected pork products and blood transfusion.
      We summarised the epidemiology of HEV infections among blood donors and also
      outlined any strategies to prevent transfusion-transmitted HEV, in 11 European
      countries. In response to the threat posed by HEV and related public and
      political concerns, most of the observed countries determined seroprevalence of
      HEV in donors and presence of HEV RNA in blood donations. France, Germany, Spain
      and the United Kingdom (UK) reported cases of transfusion-transmitted HEV.
      Ireland and the UK have already implemented HEV RNA screening of blood donations;
      the Netherlands will start in 2017. Germany and France perform screening for HEV
      RNA in several blood establishments or plasma donations intended for use in high
      risk patients respectively and, with Switzerland, are considering implementing
      selective or universal screening nationwide. In Greece, Portugal, Italy and
      Spain, the blood authorities are evaluating the situation. Denmark decided not to
      implement the HEV screening of blood donations.

PMID- 28449731
TI  - Estimating the annual burden of tick-borne encephalitis to inform vaccination
      policy, Slovenia, 2009 to 2013.
AB  - With an annual incidence between 8 and 15 per 100,000 population in the period
      from 2009 to 2013, Slovenia has one of the highest notified incidences of tick
      borne encephalitis (TBE) in Europe. TBE vaccination coverage remains at about
      7.3%. To inform vaccination policy, we used surveillance data from 2009 to 2013
      to calculate the overall and age- and sex-specific mean annual TBE incidence. We
      estimated disability-adjusted life years (DALYs) with 95% uncertainty intervals
      (UI), using the Burden of Communicable Diseases in Europe approach from the
      European Centre for Disease Prevention and Control. The mean annual incidence was
      11.6 per 100,000 population, peaking in older age groups (50-74 years:
      18.5/100,000) while relatively lower among children (5-14 years: 10.2/100,000).
      We estimated an overall 10.95 DALYs per 100,000 population per year (95% UI:
      10.25-11.65). In contrast to the TBE incidence, the disease burden in children
      aged 5-14 years was higher than in adults aged 50-74 years: 17.31 (95% UI: 14.58
      20.08) and 11.58 (95% UI: 10.25-12.91) DALYs per 100,000 stratum-specific
      population, respectively. In a limited resource setting where prioritisation of
      TBE vaccination strategies is required, vaccination programmes targeting children
      may have a higher impact on disease burden.

PMID- 28449732
TI  - Three cases of mcr-1-positive colistin-resistant Escherichia coli bloodstream
      infections in Italy, August 2016 to January 2017.
AB  - We describe three cases of bloodstream infection caused by colistin-resistant
      Escherichia coli in patients in a tertiary hospital in Italy, between August 2016
      and January 2017. Whole genome sequencing detected the mcr-1 gene in three
      isolated strains belonging to different sequence types (STs). This occurrence of
      three cases with mcr-1-positive E. coli belonging to different STs in six months
      suggests a widespread problem in settings where high multidrug resistance is
      endemic such as in Italy.

PMID- 28449733
TI  - Erratum for Euro Surveill. 2017;22(14).

PMID- 28449734
TI  - Concern regarding the alleged spread of hypervirulent lymphogranuloma venereum
      Chlamydia trachomatis strain in Europe.

PMID- 28449736
TI  - Predictors of hepatitis B vaccination status in healthcare workers in Belgrade,
      Serbia, December 2015.
AB  - Despite the availability of a safe and effective vaccine since 1982, overall
      coverage of hepatitis B vaccination among healthcare workers (HCWs) has not
      reached a satisfactory level in many countries worldwide. The aim of this study
      was to estimate the prevalence of hepatitis B vaccination, and to assess the
      predictors of hepatitis B vaccination status among HCWs in Serbia. Of 380
      randomly selected HCWs, 352 (92.6%) were included in the study. The prevalence of
      hepatitis B vaccination acceptance was 66.2%. The exploratory factor analyses
      using the vaccination-refusal scale showed that items clustered under 'threat of
      disease' explained the highest proportion (30.4%) of variance among those
      declining vaccination. The factor analyses model of the potential reasons for
      receiving the hepatitis B vaccine showed that 'social influence' had the highest
      contribution (47.5%) in explaining variance among those vaccinated. In the
      multivariate adjusted model the following variables were independent predictors
      of hepatitis B vaccination status: occupation, duration of work experience,
      exposure to blood in the previous year, and total hepatitis B-related knowledge
      score. Our results highlight the need for well-planned national policies,
      possibly including mandatory hepatitis B immunisation, in the Serbian healthcare
      environment.

PMID- 28449735
TI  - Maternal pertussis immunisation: clinical gains and epidemiological legacy.
AB  - The increase in whooping cough (pertussis) incidence in many countries with high
      routine vaccination coverage is alarming, with incidence in the US reaching
      almost 50,000 reported cases per year, reflecting incidence levels not seen since
      the 1950s. While the potential explanations for this resurgence remain debated,
      we face an urgent need to protect newborns, especially during the time window
      between birth and the first routine vaccination dose. Maternal immunisation has
      been proposed as an effective strategy for protecting neonates, who are at higher
      risk of severe pertussis disease and mortality. However, if maternally derived
      antibodies adversely affect the immunogenicity of the routine schedule, through
      blunting effects, we may observe a gradual degradation of herd immunity. 'Wasted'
      vaccines would result in an accumulation of susceptible children in the
      population, specifically leading to an overall increase in incidence in older age
      groups. In this Perspective, we discuss potential long-term epidemiological
      effects of maternal immunisation, as determined by possible immune interference
      outcomes.

PMID- 28449737
TI  - Authors'reply: Concern regarding the alleged spread of hypervirulent
      lymphogranuloma venereum Chlamydia trachomatis strain in Europe.

PMID- 28449738
TI  - Indistinguishable NDM-producing Escherichia coli isolated from recreational
      waters, sewage, and a clinical specimen in Ireland, 2016 to 2017.
AB  - In this study, New Delhi metallo-beta-lactamase (NDM)-producing
      Enterobacteriaceae were identified in Irish recreational waters and sewage.
      Indistinguishable NDM-producing Escherichia coli by pulsed-field gel
      electrophoresis were isolated from sewage, a fresh water stream and a human
      source. NDM-producing Klebsiella pneumoniae isolated from sewage and seawater in
      the same area were closely related to each other and to a human isolate. This
      raises concerns regarding the potential for sewage discharges to contribute to
      the spread of carbapenemase-producing Enterobacteriaceae.

PMID- 28449740
TI  - A national imperative: Oral health services in Medicare.

PMID- 28449741
TI  - Reconstructing jaw defects.

PMID- 28449742
TI  - Authors' response.

PMID- 28449743
TI  - Correction.

PMID- 28449744
TI  - Correction.

PMID- 28449745
TI  - Lithium disilicate single crowns demonstrate favorable clinical outcomes in 1
      through 5 years compared with lithium disilicate fixed prostheses.

PMID- 28449746
TI  - How to manage short-term staff member absences.

PMID- 28449747
TI  - What are the ethical concerns of inadequate clinical calibration of dental
      practitioners within the same group practice?

PMID- 28449748
TI  - Breast-feeding up to 11 months associated with lower decayed, missing, and filled
      surfaces index and lower caries prevalence up to 4 years of age.

PMID- 28449749
TI  - No evidence of an association between caries at age 6 years and oral health
      related quality of life at age 10 years.

PMID- 28449750
TI  - Low incidence and slow progression of caries in children consuming polyol
      containing candies, but no differences important to patients consuming polyols.

PMID- 28449751
TI  - Preoperative oral ibuprofen and oxicam analgesics increase the rate of successful
      anesthesia of mandibular molars with irreversible pulpitis.

PMID- 28449752
TI  - Implant-supported and tooth-supported single crowns fabricated with lithium
      disilicate seem to have a high 10-year survival rate.

PMID- 28449753
TI  - Regular oral health education is effective in reducing caries incidence whereas
      fluoride varnish seems to have no added benefit.

PMID- 28449754
TI  - Insufficient evidence for preferring 2% articaine over 4% articaine in patients
      undergoing mandibular premolar or molar extractions.

PMID- 28449755
TI  - Reciprocating single-file and multifile rotary instrumentation techniques likely
      to result in less pain after endodontic treatment of asymptomatic necrotic
      mandibular molars with periapical lesions.

PMID- 28449756
TI  - Severe tooth wear has a negative psychological impact, but it is not related to
      overall oral health-related quality of life.

PMID- 28449757
TI  - No evidence of an association between an allergy to dental materials and dental
      hygiene products and symptomatic oral lesions.

PMID- 28449758
TI  - Anxiety related to dental treatment is probably associated with perceived pain,
      but the magnitude of this association remains unclear.

PMID- 28449759
TI  - Titanium-zirconium narrow-diameter implants may have good outcomes, but there is
      insufficient evidence to support their overall performance success.

PMID- 28449760
TI  - Obesity is not associated with low arch tooth alignment time in adolescents
      undergoing treatment with fixed appliances.

PMID- 28449762
TI  - No evidence of benefits from using enamel matrix derivative as an adjuvant
      treatment in patients with peri-implant mucositis.

PMID- 28449761
TI  - High survival and clinical success rates, but also high discoloration rates, in
      immature necrotic teeth treated with regenerative endodontic procedures.

PMID- 28449763
TI  - Early orthodontic treatment produces short-term dental and skeletal changes in
      patients with Class III malocclusions.

PMID- 28449764
TI  - Probing depth and implant location are risk factors for bleeding on probing
      around dental implants.

PMID- 28449765
TI  - Cell phone use may increase the risk of developing parotid gland tumors.

PMID- 28449766
TI  - Active caries, consequences of untreated caries, and tooth pain relate to only a
      small decrease in older adults' quality of life.

PMID- 28449767
TI  - Mini implants seem to have good prognosis when used to support complete
      overdentures.

PMID- 28449768
TI  - Submucosal dexamethasone reduces pain, swelling, and trismus after impacted third
      molar extraction.

PMID- 28449769
TI  - Antimicrobial photodynamic therapy was not effective as an adjuvant treatment for
      deep periodontal pockets.

PMID- 28449770
TI  - Early Mortality After Catheter Ablation of Ventricular Tachycardia in Patients
      With Structural Heart Disease.
AB  - BACKGROUND: In patients referred for radiofrequency catheter ablation (RFCA) of
      ventricular tachycardia (VT) in the setting of structural heart disease, early
      post-procedural mortality (EM) has not been previously investigated. OBJECTIVES:
      The purpose of this study was to evaluate EM after catheter ablation of scar
      related VT. METHODS: Associations between clinical and procedural variables and
      EM (within 31 days of the procedure) were tested in patients with structural
      heart disease undergoing RFCA of VT at 12 international centers. RESULTS: Of
      2,061 patients (mean age 62 +/- 13 years; left ventricular ejection fraction
      [LVEF] 34 +/- 13%; 53% ischemic etiology), EM occurred in 100 (5%; 95% confidence
      interval [CI]: 4% to 6%). A total of 54 (3%) patients died before hospital
      discharge (median 9 days after the procedure; 25% for refractory VT), including
      12 (0.6%) after a major procedure-related complication. In multivariable
      analysis, the following factors were found to be significantly associated with
      EM: LVEF (odds ratio [OR] per percent decrease: 1.12; 95% CI: 1.05 to 1.20; p <
      0.001), chronic kidney disease (OR: 2.73; 95% CI: 1.10 to 6.80; p = 0.030),
      presentation with VT storm (OR: 3.61; 95% CI: 1.37 to 9.48; p = 0.009), and
      presence of unmappable VTs (OR: 5.69; 95% CI: 1.37 to 23.69; p = 0.017).
      Recurrent VT was also associated with an increased risk of subsequent death
      (hazard ratio: 7.19; 95% CI: 5.57 to 9.28; p < 0.001) and EM (hazard ratio:
      11.45; 95% CI: 7.47 to 17.59; p < 0.001). CONCLUSIONS: In a contemporary cohort
      of patients with scar-related VT undergoing RFCA, EM occurred in 5% of cases.
      Clinical and procedural variables indicating poorer clinical status (low LVEF,
      chronic kidney disease, VT storm, and unmappable VTs) and post-procedural VT
      recurrence may predict EM. Identification of such features may prompt early
      consideration for hemodynamic support or other care to help mitigate later
      potential complications.

PMID- 28449771
TI  - Risk Factors for Early Mortality After VT Ablation: How Sick Is too Sick?

PMID- 28449772
TI  - Cardiac Resynchronization Therapy With Wireless Left Ventricular Endocardial
      Pacing: The SELECT-LV Study.
AB  - BACKGROUND: A total of 30% to 40% of patients with congestive heart failure
      eligible for cardiac resynchronization therapy (CRT) either do not respond to
      conventional CRT or remain untreated due to an inability or impediment to
      coronary sinus (CS) lead implantation. The WiSE-CRT system (EBR Systems,
      Sunnyvale, California) was developed to address this at-risk patient population
      by performing biventricular pacing via a wireless left ventricular (LV)
      endocardial pacing electrode. OBJECTIVES: The SELECT-LV (Safety and Performance
      of Electrodes implanted in the Left Ventricle) study is a prospective multicenter
      non-randomized trial assessing the safety and performance of the WiSE-CRT system.
      METHODS: A total of 35 patients indicated for CRT who had "failed" conventional
      CRT underwent implantation of an LV endocardial pacing electrode and a
      subcutaneous pulse generator. System performance, clinical efficacy, and safety
      events were assessed out to 6 months post-implant. RESULTS: The procedure was
      successful in 97.1% (n = 34) of attempted implants. The most common indications
      for endocardial LV pacing were difficult CS anatomy (n =12), failure to respond
      to conventional CRT (n = 10), and a high CS pacing threshold or phrenic nerve
      capture (n = 5). The primary performance endpoint, biventricular pacing on the 12
      lead electrocardiogram at 1 month, was achieved in 33 of 34 patients. A total of
      28 patients (84.8%) had improvement in the clinical composite score at 6 months,
      and 21 (66%) demonstrated a positive echocardiographic CRT response (>=5%
      absolute increase in LV ejection fraction). There were no pericardial effusions,
      but serious procedure/device-related events occurred in 3 patients (8.6%) within
      24 h, and 8 patients (22.9%) between 24 h and 1 month. CONCLUSIONS: The SELECT-LV
      study demonstrates the clinical feasibility for the WiSE-CRT system, and provided
      clinical benefits to a majority of patients within an otherwise "failed" CRT
      population. (Safety and Performance of Electrodes Implanted in the Left Ventricle
      [SELECT-LV]; NCT01905670).

PMID- 28449773
TI  - Leadless Left Ventricular Pacing: Another Step Toward Improved CRT Response.

PMID- 28449775
TI  - Holistic Approach to Determine Cause of Autopsy-Negative Sudden Natural Death.

PMID- 28449774
TI  - Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death
      Syndrome.
AB  - BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with
      negative autopsy and toxicological analysis. Cardiac genetic disease is a likely
      etiology. OBJECTIVES: This study investigated the clinical utility and combined
      yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and
      comprehensive clinical evaluation of surviving relatives. METHODS: We evaluated
      302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65%
      males) who underwent next-generation sequencing using an extended panel of 77
      primary electrical disorder and cardiomyopathy genes. Pathogenic and likely
      pathogenic variants were classified using American College of Medical Genetics
      (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical
      evaluation in 82 surviving families was evaluated. A gene-level rare variant
      association analysis was conducted in SADS cases versus controls. RESULTS: A
      clinically actionable pathogenic or likely pathogenic variant was identified in
      40 of 302 cases (13%). The main etiologies established were catecholaminergic
      polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%],
      respectively). Gene-based rare variants association analysis showed enrichment of
      rare predicted deleterious variants in RYR2 (p = 5 * 10-5). Combining molecular
      autopsy with clinical evaluation in surviving families increased diagnostic yield
      from 26% to 39%. CONCLUSIONS: Molecular autopsy for electrical disorder and
      cardiomyopathy genes, using ACMG guidelines for variant classification,
      identified a modest but realistic yield in SADS. Our data highlighted the
      predominant role of catecholaminergic polymorphic ventricular tachycardia and
      long QT syndrome, especially the RYR2 gene, as well as the minimal yield from
      other genes. Furthermore, we showed the enhanced utility of combined clinical and
      genetic evaluation.

PMID- 28449776
TI  - Incident Myocardial Infarction and Very Late Stent Thrombosis in Outpatients With
      Stable Coronary Artery Disease.
AB  - BACKGROUND: Current data are lacking for incidence, correlates, and prognosis
      associated with incident myocardial infarction (MI) in patients with stable
      coronary artery disease (CAD). Furthermore, the contribution of very late stent
      thrombosis (VLST) to these events remains poorly understood. OBJECTIVES: This
      study aimed to analyze the residual risk of MI, together with relevant associated
      factors, and related mortality in stable CAD outpatients. METHODS: The
      multicenter CORONOR (Suivi d'une cohorte de patients COROnariens stables en
      region NORd-Pas-de-Calais) study enrolled 4,184 unselected outpatients with
      stable CAD (i.e., MI or coronary revascularization >1 year previously). Five-year
      follow-up was achieved for 4,094 patients (98%). RESULTS: We identified a linear
      risk of incident MI (0.8% annually), with ST-segment elevation MI constituting
      one-third of all cases. Current smoking, low-density lipoprotein cholesterol,
      multivessel CAD, diabetes with glycosylated hemoglobin >7%, and persistent angina
      were all associated with increased risk, and prior bypass surgery was associated
      with decreased risk. When used as a time-dependent variable, incident MI was
      associated with an increased risk of death (hazard ratio: 2.05; p < 0.0001).
      Among patients with prior stent implantation, VLST was causal in 20% of MI cases
      and presented more often as ST-segment elevation MI versus MI not related to a
      stented site (59% vs. 26%, p = 0.001). Adjusted mortality was 4 times higher in
      patients with VLST than in MI not related to a stented site. CONCLUSIONS: In
      stable CAD outpatients, incident MI occurs at a stable rate of 0.8% annually, is
      related to VLST in one-fifth of cases, and is associated with an increased
      mortality risk, especially for VLST. Multivessel CAD and residual uncontrolled
      risk factors are strongly associated with MI.

PMID- 28449777
TI  - On the Stability of Stable Coronary Artery Disease.

PMID- 28449779
TI  - Defining Tachycardia-Induced Cardiomyopathy: Life in the Fast Lane.

PMID- 28449778
TI  - Histopathological and Immunological Characteristics of Tachycardia-Induced
      Cardiomyopathy.
AB  - BACKGROUND: Tachycardiomyopathy or tachycardia-induced cardiomyopathy (TCM) has
      been known for decades as a reversible form of nonischemic cardiomyopathy.
      However, its mechanism and properties remain poorly understood. OBJECTIVES: The
      current study investigated endomyocardial biopsy samples from patients with TCM
      and compared them with samples from patients with dilated cardiomyopathy (DCM)
      and inflammatory cardiomyopathy (ICM). METHODS: The study included 189 patients
      with new-onset heart failure and severely reduced ejection fraction not caused by
      valvular or ischemic heart disease. Nineteen patients retrospectively fulfilled
      common criteria of TCM, 79 patients had a diagnosis of DCM, and 91 had a
      diagnosis of ICM. RESULTS: Patients with TCM, on the basis of clinical criteria,
      had stronger myocardial expression of major histocompatibility complex class II
      molecule and enhanced infiltration of CD68+ macrophages compared with patients
      with DCM. Furthermore, when compared with patients with ICM, the presence of T
      cells and macrophages was significantly reduced in TCM. Myocardial fibrosis was
      detected to a significantly lower degree in patients with TCM compared with
      patients with DCM and ICM. Electron microscopic examination revealed severe
      structural changes in patients with TCM. A disturbed distribution pattern of
      mitochondria was predominantly present in TCM. Quantitative assessment of myocyte
      morphology revealed significantly enhanced myocyte size compared with patients
      with ICM. Ribonucleic acid expression analysis identified changes in metabolic
      pathways among the patient groups. CONCLUSIONS: TCM is characterized by changes
      in cardiomyocyte and mitochondrial morphology accompanied by a macrophage
      dominated cardiac inflammation. Thus, further prospective studies are warranted
      to characterize patients with TCM by endomyocardial biopsy more clearly.

PMID- 28449780
TI  - Transcatheter Mitral Valve Replacement: Insights From Early Clinical Experience
      and Future Challenges.
AB  - Transcatheter mitral valve repair, particularly edge-to-edge leaflet repair, is a
      well-established alternative for patients with severe primary mitral
      regurgitation (MR) considered at high or prohibitive surgical risk. More
      recently, transcatheter mitral valve replacement (TMVR) has emerged as a
      potential therapeutic option for the treatment of severe MR. TMVR may offer some
      advantages over transcatheter repair by providing a more complete and
      reproducible MR reduction. Several devices are under preclinical and clinical
      evaluation, and the early experience with more than 100 patients has demonstrated
      the feasibility of TMVR. In this review, we describe the TMVR systems currently
      in development and the results obtained from early clinical experiences. We also
      discuss the main challenges in and future perspectives on this emerging field.
      Future studies with a much larger number of patients are needed to provide
      consistent safety and efficacy data on each of the TMVR systems.

PMID- 28449782
TI  - Health Services Research: Cardiology in the Changing Health Care Landscape.

PMID- 28449783
TI  - Effect of Ticagrelor Versus Clopidogrel on Vascular Reactivity.

PMID- 28449781
TI  - Bioprosthetic Valve Thrombosis.
AB  - Bioprosthetic valve (BPV) thrombosis is considered a relatively rare clinical
      entity. Yet a more recent analysis involving a more systematic echocardiographic
      follow-up, the advent of transcatheter heart valve (THV) technologies coupled
      with the highly sensitive nature of 4-dimensional computed tomographic imaging
      for detecting subclinical thrombi upon both surgically implanted and THVs, has
      generated enormous interest in this field, casting new light on both its true
      incidence and clinical relevance. Debate continues among clinicians as to both
      the clinical relevance of subclinical BPV thrombosis and the value of empirical
      oral anticoagulation following BPV implantation. Furthermore, currently no
      systematic, prospective data exist regarding the optimal treatment approach in
      THV recipients. The authors provide an overview of the clinical and subclinical
      spectrum of BPV thrombosis of surgical and THVs, outline its diagnostic
      challenges, summarize its pathophysiological basis, and discuss various
      therapeutic options that are emerging, particularly within the rapidly expanding
      field of THV implantation.

PMID- 28449785
TI  - To Add or Not to Add Mitral Valve Surgery to Septal Myectomy in HOCM Patients.

PMID- 28449784
TI  - Apolipoprotein A-IV-Associated Cardiac Amyloidosis.

PMID- 28449786
TI  - Reply: To Add or Not to Add Mitral Valve Surgery to Septal Myectomy in HOCM
      Patients.

PMID- 28449788
TI  - Reply: Cardiopulmonary Exercise Testing Versus 6-Min Walk Test as Clinically
      Meaningful Endpoints in HF Trials.

PMID- 28449787
TI  - Cardiopulmonary Exercise Testing Versus 6-Min Walk Test as Clinically Meaningful
      Endpoints in HF Trials.

PMID- 28449789
TI  - A Year Later: Lessons Learned.

PMID- 28449790
TI  - Author's Response.

PMID- 28449791
TI  - Psyllium Husk Should Be Taken at Higher Dose with Sufficient Water to Maximize
      Its Efficacy.

PMID- 28449792
TI  - Academy Approves NIAID Addendum Guidelines for the Prevention of Peanut Allergy.

PMID- 28449794
TI  - Methylmercury and Seafood: What Are the Latest Guidelines?

PMID- 28449793
TI  - Addendum Guidelines for the Prevention of Peanut Allergy in the United States:
      Summary of the National Institute of Allergy and Infectious Diseases-Sponsored
      Expert Panel.

PMID- 28449796
TI  - Theory and Fact: Revisiting Association and Causation.

PMID- 28449795
TI  - Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity
      and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of
      the ENABLE Trials.
AB  - OBJECTIVES: The objective of this clinical trial was to evaluate the long-term
      effect of endothelin receptor antagonism with bosentan on the morbidity and
      mortality of patients with severe chronic heart failure. BACKGROUND: Endothelin
      may play a role in heart failure, but short-term clinical trials with endothelin
      receptor antagonists have reported disappointing results. Long-term trials are
      lacking. METHODS: In 2 identical double-blind trials, we randomly assigned 1,613
      patients with New York Heart Association functional class IIIb to IV heart
      failure and an ejection fraction <35% to receive placebo or bosentan (target dose
      125 mg twice daily) for a median of 1.5 years. The primary outcome for each trial
      was clinical status at 9 months (assessed by the hierarchical clinical
      composite); the primary outcome across the 2 trials was death from any cause or
      hospitalization for heart failure. RESULTS: Bosentan did not influence clinical
      status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321
      patients in the placebo group and 312 patients in the bosentan group died or were
      hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval
      [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention
      within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight
      gain, decreases in hemoglobin, and an increased risk of hospitalization for heart
      failure, despite intensification of background diuretics. During follow-up, 173
      patients died in the placebo group and 160 patients died in the bosentan group
      (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed
      meaningful increases in hepatic transaminases, but none had acute or chronic
      liver failure. CONCLUSIONS: Bosentan did not improve the clinical course or
      natural history of patients with severe chronic heart failure and but caused
      early and important fluid retention.

PMID- 28449798
TI  - Physical Activity Prevents Obesity and Heart Failure: Now What Are We Going to Do
      About It?

PMID- 28449797
TI  - Physical Activity, Obesity, and Subclinical Myocardial Damage.
AB  - OBJECTIVES: This study sought to evaluate the association of physical activity
      with chronic myocardial damage, assessed by elevated high-sensitivity cardiac
      troponin T (hs-cTnT), in individuals with and without obesity. BACKGROUND:
      Physical activity is associated with reduced risk of heart failure (HF),
      particularly among obese people. The role of chronic myocardial damage in this
      association is uncertain. METHODS: We studied 9,427 participants in the
      Atherosclerosis Risk in Communities Study without cardiovascular disease, with
      body mass index >18.5 kg/m2. Physical activity was categorized per American Heart
      Association guidelines as recommended, intermediate, or poor. We evaluated cross
      sectional associations of physical activity and obesity with elevated hs-cTnT
      (>=14 ng/l). In prospective analyses, we quantified the association of elevated
      hs-cTnT with HF risk within cross-categories of baseline physical activity and
      obesity. RESULTS: People with poor physical activity were more likely to have
      elevated hs-cTnT than those with recommended levels (odds ratio [OR]: 1.39; 95%
      confidence interval [CI]: 1.15 to 1.68). In cross-categories of physical activity
      and obesity, using the non-obese/recommended activity group as the reference,
      individuals with obesity and poor activity were most likely to have elevated hs
      cTnT (OR: 2.46; 95% CI: 1.91 to 3.19), whereas the obese/recommended activity
      group had a weaker association (OR: 1.68; 95% CI: 1.28 to 2.21; p < 0.001 for
      interaction between physical activity and obesity). In prospective analyses,
      elevated hs-cTnT was strongly associated (p < 0.001) with incident HF in all
      obesity/physical activity cross-categories (p > 0.20 for interaction).
      CONCLUSIONS: Physical activity is inversely associated with chronic subclinical
      myocardial damage. Physical activity might lessen the association between obesity
      and subclinical myocardial damage, which could represent a mechanism by which
      physical activity reduces HF risk.

PMID- 28449800
TI  - High Heart Failure Readmission Rates: Is It the Health System's Fault?

PMID- 28449799
TI  - Impact of Current Versus Previous Cardiac Resynchronization Therapy Guidelines on
      the Proportion of Patients With Heart Failure Eligible for Therapy.
AB  - OBJECTIVES: This study sought to ascertain the impact of heart failure (HF)
      guideline change on the number of patients eligible to undergo cardiac
      resynchronization therapy (CRT). BACKGROUND: The 2013 HF guideline of the
      American College of Cardiology Foundation and American Heart Association
      (ACCF/AHA) narrowed the recommendations for CRT. The impact of this guideline
      change on the number of eligible patients for CRT has not been described.
      METHODS: Using data from Get With The Guidelines-Heart Failure between 2012 and
      2015, this study evaluated the proportion of hospitalized patients with HF who
      were eligible for CRT on the basis of historical and current guideline
      recommendations. The authors identified 25,102 hospitalizations for HF that
      included patients with a left ventricular ejection fraction (LVEF) <=35% from 283
      hospitals. Patients with a medical, system-related, or patient-related reason for
      not undergoing CRT were excluded. RESULTS: Overall, 49.1% (n = 12,336) of
      patients with HF, an LVEF <=35%, and no documented contraindication were eligible
      for CRT on the basis of historical guidelines, and 33.1% (n = 8,299) of patients
      were eligible for CRT on the basis of current guidelines, a 16.1% absolute
      reduction in eligibility (p < 0.0001). Patients eligible for CRT on the basis of
      current guidelines were more likely to have CRT with an implantable cardioverter
      defibrillator or CRT with pacing only placed or prescribed at discharge (57.8%
      vs. 54.9%; p < 0.0001) compared with patients eligible for CRT on the basis of
      historical guidelines. CONCLUSIONS: In this population of patients with HF, an
      LVEF <=35%, and no documented contraindication for CRT, the current ACCF/AHA HF
      guidelines reduce the proportion of patients eligible for CRT by approximately
      15%.

PMID- 28449801
TI  - Risk Stratification in Dilated Cardiomyopathy: Is the Arrhythmogenic Substrate
      Stable Over Time?

PMID- 28449802
TI  - Reply: Risk Stratification in Dilated Cardiomyopathy: Is the Arrhythmogenic
      Substrate Stable Over Time?

PMID- 28449803
TI  - Observational Versus Randomized: Sliding Toward Nonevidence-Based Medicine.

PMID- 28449804
TI  - Reply: Observational Versus Randomized: Sliding Toward Nonevidence-Based
      Medicine.

PMID- 28449805
TI  - Spectrum of mismatch repair gene mutations and clinical presentation of Hispanic
      individuals with Lynch syndrome.
AB  - Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is
      caused by mismatch repair (MMR) gene mutations. However, data about MMR mutations
      in Hispanics are limited. This study aims to describe the spectrum of MMR
      mutations in Hispanics with LS and explore ancestral origins. This case series
      involved an IRB-approved retrospective chart review of self-identified Hispanic
      patients (n = 397) seen for genetic cancer risk assessment at four collaborating
      academic institutions in California, Texas, and Puerto Rico who were evaluated by
      MMR genotyping and/or tumor analysis. A literature review was conducted for all
      mutations identified. Of those who underwent clinical genetic testing (n = 176),
      71 had MMR gene mutations. Nine mutations were observed more than once. One third
      (3/9) of recurrent mutations and two additional mutations (seen only once) were
      previously reported in Spain, confirming the influence of Spanish ancestry on MMR
      mutations in Hispanic populations. The recurrent mutations identified (n = 9)
      included both previously reported mutations as well as unique mutations not in
      the literature. This is the largest report of Hispanic MMR mutations in North
      America; however, a larger sample and haplotype analyses are needed to better
      understand recurrent MMR mutations in Hispanic populations.

PMID- 28449806
TI  - Gene fusions PAFAH1B1-USP6 and RUNX2-USP6 in aneurysmal bone cysts identified by
      next generation sequencing.
AB  - Aneurysmal bone cyst (ABC) is a locally aggressive, expansile, typically
      multilocular cystic bone tumor. ABC was previously thought to be a non-neoplastic
      lesion; however, it is now considered to be neoplasm that features recurrent
      chromosomal translocations resulting in gene fusions between ubiquitin specific
      peptidase 6 (USP6) and multiple partners, including COL1A1, CDH11, TRAP150, ZNF90
      and OMD. Using next generation sequencing (NGS), we uncovered two fusion partners
      of USP6 in two ABCs: platelet activating factor acetylhydrolase 1b regulatory
      subunit 1 (PAFAH1B1), which is known to contribute to tumorigenesis in lung
      cancer, and runt-related transcription factor 2 (RUNX2), which is known to
      regulate osteoblastic differentiation, osteosarcoma tumorigenesis and its
      metastasis. In our study, the PAFAH1B1-USP6 fusion consisted of the promoter of
      PAFAH1B1 fused to the 5'-untranslated region (5'-UTR) of USP6 and was discovered
      in a typical ABC. The RUNX2-USP6 fusion had the promoter and a short coding
      region of RUNX2 fused to the translation start codon of USP6 and was detected in
      an unusually aggressive ABC with an osteosarcoma-like soft tissue extension. Our
      findings not only expanded the repertoire of the partner genes of USP6 in ABC but
      also can serve as a reference for future studies to better understand the
      correlation between various gene fusions and the progression of ABC.

PMID- 28449807
TI  - Cancer in Machado-Joseph disease patients-low frequency as a cause of death.
AB  - Since polyglutamine diseases have been related to a reduced risk of cancer, we
      aimed to study the 15 years cumulative incidence of cancer (CIC) (arm 1) and the
      proportion of cancer as a cause of death (arm 2) in symptomatic carriers of
      spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). SCA3/MJD and
      control individuals from our state were invited to participate. A structured
      interview was performed. CIC as published by the Brazilian National Institute of
      Cancer, was used as populational control. Causes of death were obtained from the
      Public Information System on Mortality. We interviewed 154 SCA3/MJD patients and
      80 unrelated controls: CIC was 7/154 (4.5%) and 5/80 (6.3%), respectively. The
      interim analysis for futility showed that the number of individuals required to
      detect a significant difference between groups (1938) would be three times larger
      than the existing local SCA3/MJD population (625), for an absolute risk reduction
      of 1.8%. Then this study arm was discontinued due to lack of power. In the same
      period, cancer was a cause of death in 9/101 (8.9%) SCA3/MJD and in 52/202
      (26.2%) controls, with an absolute reduction risk of 17.3% (OR 0.27, 95%CI 0.13
      to 0.58, p = 0.01). A significant reduction of cancer as cause of death was
      observed in SCA3/MJD, suggesting a common effect to all polyglutamine diseases.

PMID- 28449808
TI  - Validation of quantitative PCR-based assays for detection of gene copy number
      aberrations in formalin-fixed, paraffin embedded solid tumor samples.
AB  - Gene copy number changes are important somatic alterations in cancers. A number
      of high throughput methods, such as next generation sequencing, are capable of
      detecting copy number aberrations, but their use can be challenging and cost
      prohibitive for screening a small number of markers. Furthermore, detection of
      CNAs by high throughput platforms needs confirmation by an orthogonal technique,
      especially in cases with low level CNAs. Here, we have validated TaqMan based
      quantitative PCR (qPCR) assays to detect CNAs in genes of high clinical
      importance in formalin-fixed, paraffin-embedded (FFPE) samples. A cohort of 22
      tumors of various types that harbor 67 CNAs in 13 genes was assessed. The
      abnormalities in these tumors were detected by using a NGS-based 50 gene hotspot
      panel on Ion Torrent PGM and molecular inversion probe (MIP) array. The CNAs
      included ERBB2 (n = 6), PDGFRA (n = 6), KIT (n = 7), NRAS (n = 3), PIK3CA (n =
      6), MYC (n = 7), MET (n = 4), FLT3 (n = 6), FGFR3 (n = 3), FGFR2 (n = 3), EGFR (n
      = 7), KRAS (n = 6) and FGFR1 (n = 5). Different amounts of input DNA were tested
      and 5 ng FFPE DNA was found to be adequate without limiting detection
      sensitivity. All 22 (100%) positive tumor samples revealed by MIP array were
      confirmed by real time qPCR and 17 of 22 (77.2%) samples tested by NGS were
      confirmed. The limit of detection of the qPCR assay was determined by serial
      dilution of SKBR3 cell line DNA (with amplified ERBB2) and showed an ability to
      detect 3 copies consistently up to 0.75% dilution. The ability to use low input
      of FFPE DNA, high sensitivity, and short turnaround time makes qPCR a valuable
      and economically viable platform for detecting single gene CNAs as well as for
      confirmation of CNAs detected by high throughput screening assays.

PMID- 28449809
TI  - Genomic diagnostics leading to the identification of a TFG-ROS1 fusion in a child
      with possible atypical meningioma.
AB  - Meningiomas are rare in children. They are highly complex, harboring unique
      clinical and pathological characteristics, and many occur in patients with
      neurofibromatosis type 2. Hereby, we present a case of a two-year-old boy
      presented with a diagnostically challenging intraventricular tumor. It was
      incompletely resected 6 times over 14 months but kept progressing and was
      ultimately deemed unresectable. Histologically, the tumor was initially
      classified as schwannoma, but extensive international review concluded it was
      most likely an atypical meningioma, WHO grade II. Comprehensive genomic profiling
      revealed a TFG-ROS1 fusion, suggesting that ROS1-signaling pathway alterations
      were driving the tumor growth. In light of this new information, the possibility
      of a diagnosis of inflammatory myofibroblastic tumor was considered; however the
      histopathological results were not conclusive. This specific molecular finding
      allowed the potential use of precision medicine and the patient was enrolled in
      the AcSe phase 2 trial with crizotinib (NCT02034981), leading to a prolonged
      partial tumor response which is persisting since 14 months. This case highlights
      the value of precision cancer medicine in children.

PMID- 28449810
TI  - Novel t(5;11)(q32;q13.4) with NUMA1-PDGFRB fusion in a myeloid neoplasm with
      eosinophilia with response to imatinib mesylate.
AB  - We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with
      eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A
      t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified
      by metaphase chromosome analysis, and rearrangement of the platelet-derived
      growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using
      a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH
      mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13.4 to a
      150 kb genomic region containing three genes, including NUMA1. Mate pair
      sequencing analysis demonstrated NUMA1-PDGFRB fusion. The fusion protein includes
      coiled-coil domains of nuclear mitotic apparatus protein 1 (NuMA1, involved in
      protein homodimerization and heteroassociation) and tyrosine kinase domains of
      PDGFRB. Diverse rearrangements involving the PDGFRB gene have been identified in
      myeloid and lymphoid neoplasms with eosinophilia, but rearrangement of the
      nuclear mitotic apparatus protein 1 (NUMA1) gene has previously been reported in
      a human malignancy in only one instance, a NUMA1-RARA fusion caused by a t(11;17)
      translocation in a patient with acute promyelocytic leukemia. The NUMA1-PDGFRB
      fusion is the second instance of rearrangement of NUMA1, encoding an element of
      the mitotic apparatus, in human cancer.

PMID- 28449812
TI  - From the Editor.

PMID- 28449811
TI  - Effects of polymorphisms identified in genome-wide association studies of never
      smoking females on the prognosis of non-small cell lung cancer.
AB  - A number of genome-wide association studies have reported several variants that
      influence the risk of lung cancer in never-smoking females. We evaluated the
      impact of these variants on survival outcome in never-smoking females with non
      small cell lung cancer (NSCLC). In total, 510 never-smoking females with NSCLC
      who underwent curative surgery were enrolled. Eleven variants associated with
      lung cancer susceptibility in never-smoking females were genotyped and their
      associations with survival outcome were analyzed. Among these 11 variants, TP63
      rs7631358 and CSF1R rs10079250 affected survival outcomes. TP63 rs7631358 G > A
      was associated with a relatively worse overall survival (under a dominant model;
      hazard ratio = 2.31, 95% confidence interval = 1.18-4.52, P = 0.01). CSF1R
      rs10079250 A > G was associated with a relatively better disease-free survival
      (under a codominant model; hazard ratio = 0.70, 95% confidence interval = 0.53
      0.93, P = 0.01). These results suggest that TP63 rs7631358 G > A and CSF1R
      rs10079250 A > G may affect the prognosis of NSCLC in never-smoking females, as
      well as the risk of lung cancer.

PMID- 28449814
TI  - Osteoporosis, an Update.

PMID- 28449813
TI  - Beyond remission and mucosal healing in Crohn's disease. Exploring the deep with
      cross sectional imaging.

PMID- 28449817
TI  - Correction in Article by Merchan et al. "Ventricular Support With Extracorporeal
      Membrane Oxygenation: Beyond Cardiogenic Shock Treatment". Rev Esp Cardiol.
      2015;68:897-909.

PMID- 28449818
TI  - Canine Mixed Mammary Tumour as a Model for Human Breast Cancer with Osseous
      Metaplasia.
AB  - Canine mixed mammary tumours (CMMTs) and human metaplastic breast carcinomas
      (HMBCs) share several histopathological features and risk factors. In both
      species, these tumours display epithelial and stromal components. HMBCs are rare
      malignant tumours, but CMMTs are one of the most common mammary tumours in dogs
      and are more often benign than malignant. In this study, benign (n = 88) and
      malignant (n = 13) CMMTs were characterized using specific antibodies against
      oestrogen receptor, progesterone receptor, human epidermal growth factor receptor
      2, cytokeratin 5/6, cytokeratin AE1/AE3, vimentin, Ki67, E-cadherin and p63.
      Cartilage and bone matrices associated with benign and malignant CMMTs were
      characterized using specific antibodies against BMP4, Runx2, Sox9 and
      osteopontin. The current study suggested that CMMTs are of epithelial origin, but
      display a myoepithelial-like differentiation. The findings suggest key roles for
      Sox9, Runx2 and BMP4 in chondrogenesis and bone formation in CMMTs. The high
      expression of osteopontin in CMMTs appears to be unrelated to tumour malignancy.

PMID- 28449819
TI  - The plastic in microplastics: A review.
AB  - Microplastics [MPs], now a ubiquitous pollutant in the oceans, pose a serious
      potential threat to marine ecology and has justifiably encouraged focused
      biological and ecological research attention. But, their generation, fate,
      fragmentation and their propensity to sorb/release persistent organic pollutants
      (POPs) are determined by the characteristics of the polymers that constitutes
      them. Yet, physico-chemical characteristics of the polymers making up the MPs
      have not received detailed attention in published work. This review assesses the
      relevance of selected characteristics of plastics that composes the
      microplastics, to their role as a pollutant with potentially serious ecological
      impacts. Fragmentation leading to secondary microplastics is also discussed
      underlining the likelihood of a surface-ablation mechanism that can lead to
      preferential formation of smaller sized MPs.

PMID- 28449821
TI  - Systematic review of nonoperative versus operative treatment of uncomplicated
      appendicitis.
AB  - BACKGROUND: To compare the risk of complications between initial nonoperative
      treatment and appendectomy of uncomplicated (simple) appendicitis in children.
      METHODS: Systematic literature search. Eligible for inclusion were both and
      randomized controlled trials and cohort studies including children in which the
      outcome of nonoperative treatment of uncomplicated appendicitis was reported with
      a minimum follow-up period of one year. Two authors extracted data independently
      and assessed quality. Primary outcome parameter was the percentage of children
      experiencing complications. Secondary outcomes were early failures, recurrent
      appendicitis and appendectomies, for all indications and on request. RESULTS:
      Five of the 2051 articles screened were eligible for inclusion, including 147
      children (nonoperative treatment) and 173 children (appendectomy) with one year
      follow-up. Percentage of children experiencing complications ranged from 0 to 13%
      versus 0-17% for nonoperative and appendectomy, respectively. Nonoperative
      treatment avoided an appendectomy in 62-81% of the children after one year follow
      up. CONCLUSION: The evidence base for initial nonoperative treatment of acute
      uncomplicated appendicitis in children is by far insufficient. It suggests that
      the percentage of patients experiencing complications in the initial nonoperative
      treatment group is comparable to the appendectomy group, and it may avoid an
      appendectomy in the large majority of children after one year follow-up. TYPE OF
      STUDY: Systematic review. LEVEL OF EVIDENCE: 1.

PMID- 28449822
TI  - Sliding mode disturbance observer-based control of a twin rotor MIMO system.
AB  - This work proposes a robust tracking controller for a helicopter laboratory setup
      known as the twin rotor MIMO system (TRMS) using an integral sliding mode
      controller. To eliminate the discontinuity in the control signal, the controller
      is augmented by a sliding mode disturbance observer. The actuator dynamics is
      handled using a backstepping approach which is applicable due to the continuous
      chattering-free nature of the command signals generated using the disturbance
      observer based controller. To avoid the complexity of analytically
      differentiating the command signals, a first order sliding mode differentiator is
      used. Stability analysis of the closed loop system and the ultimate boundedness
      of the tracking error is proved using Lyapunov stability arguments. The proposed
      controller is validated by several simulation studies and is compared to other
      schemes in the literature. Experimental results using a hardware-in-the-loop
      system validate the robustness and effectiveness of the proposed controller.

PMID- 28449820
TI  - Range and Heterogeneity of Outcomes in Randomized Trials of Pediatric Chronic
      Kidney Disease.
AB  - OBJECTIVE: To determine the range and heterogeneity of outcomes reported in
      randomized controlled trials of interventions for children with chronic kidney
      disease (CKD). STUDY DESIGN: The Cochrane Kidney and Transplant Specialized
      Register was searched to March 2016. Randomized trials involving children across
      all stages of CKD were selected. All outcome domains and measurements were
      extracted from included trials. The frequency and characteristics of the outcome
      domains and measures were evaluated. RESULTS: From 205 trials included, 6158
      different measurements of 100 different outcome domains were reported, with a
      median of 22 domains per trial (IQR 13-41). Overall, 52 domains (52%) were
      surrogate, 38 (38%) were clinical, and 10 (10%) were patient-reported. The 5 most
      commonly reported domains were blood pressure (76 [37%] trials),
      relapse/remission (70 [34%]), kidney function (66 [32%]), infection (61 [30%]),
      and height/pubertal development (51 [25%]). Mortality (14%), cardiovascular
      disease (4%), and quality of life (1%) were reported infrequently. The 2 most
      frequently reported outcomes, blood pressure and relapse/remission, had 56 and 81
      different outcome measures, respectively. CONCLUSIONS: The outcomes reported in
      clinical trials involving children with CKD are extremely heterogeneous and are
      most often surrogate outcomes, rather than clinical and patient-centered outcomes
      such as cardiovascular disease and quality of life. Efforts to ensure consistent
      reporting of outcomes that are important to patients and clinicians will improve
      the value of trials to guide clinical decision-making. In our study, non-English
      articles were excluded.

PMID- 28449823
TI  - The effect of handedness and laterality in a microlaryngeal surgery simulator.
AB  - PURPOSE: There are no controlled prospective studies evaluating the effect of
      dominant handedness in left- and right-sided surgery in otolaryngology.
      Endoscopic microlaryngeal phonosurgery is an ideal procedure to assess technical
      aspects of handedness and laterality, due to anatomic symmetry. In this study, we
      analyzed (1) choice of surgical approach and (2) outcomes based on handedness and
      laterality in a microlaryngeal simulator. METHODS: Using a validated high
      fidelity phonosurgery model, a prospective cohort of 19 expert laryngologists
      undertook endoscopic resection of a simulated vocal fold lesion. These resections
      were video-recorded and scored by 2 blinded expert laryngologists using a
      validated global rating scale, procedure-specific rating scale, and a hand
      preference analysis. RESULTS: There were 18 right-handed participants and 1 left
      handed. 12 left and 7 right excisions were evaluated. Cronbach's alpha for inter
      rater reliability was good (0.871, global scale; and 0.814, procedure-specific
      scale). Surgeons used their dominant hand 78.9% of the time for both incision and
      dissection. In cases where the non-dominant hand would have been preferred,
      surgeons used the non-dominant hand only 36.4% of the time for incision and
      dissection. Use of the non-dominant hand did not influence global or procedural
      rating (p=0.132 and p=0.459, respectively). CONCLUSIONS: In this simulation of
      microlaryngeal surgery, there were measurable differences in surgical approaches
      based on hand dominance, with surgeons preferring to cut and perform resection
      with the dominant hand despite limitations in the instrumentation and exposure.
      Regardless of hand preference, overall outcomes based on global rating and
      technique specific rating scales were not significantly different.

PMID- 28449825
TI  - Corrigendum to "Immunologic heterogeneity of tumor-infiltrating lymphocyte
      composition in primary melanoma" (Hum Pathol 2016;57:116-25).

PMID- 28449824
TI  - Primary mucosal melanoma of the palatine tonsil: Report of a case and review of
      the literature.
AB  - BACKGROUND: Mucosal melanoma of the palatine tonsil is extremely rare. Due to its
      poor prognosis, primary tonsillar melanoma requires prompt recognition and
      treatment. METHODS: A 62-year-old female presented with a deeply pigmented and
      exophytic lesion in the left tonsillar fossa. The patient underwent a partial
      pharyngectomy through a midline labio-mandibulotomy approach along with a left
      level I-V neck dissection. Reconstruction with a left radial forearm free flap
      and a pharyngeal constrictor advancement pharyngoplasty was performed. RESULTS:
      The patient remains free of disease at eight months after adjuvant proton therapy
      and eleven months after surgery. To our knowledge, less than thirty cases have
      been either reported or referenced in the literature since the early 1900's. This
      report is the first in English literature to compile all reported cases of
      primary tonsillar melanoma. CONCLUSION: Currently, evidence suggests that mucosal
      melanoma in the palatine tonsil should be treated in the same fashion as other
      head and neck mucosal melanomas, mindful of the high rates at which locoregional
      and distant metastases occur.

PMID- 28449826
TI  - Corrigendum to "Incidence, prevalence, mortality and causes of death in Takayasu
      Arteritis in Korea - A nationwide, population-based study" [Int. J. Cardiol.,
      235(2017), 100-104].

PMID- 28449827
TI  - Meeting Its Mission: Does Psychosomatics Align With the Mission of Its Parent
      Organization, the Academy of Psychosomatic Medicine?
AB  - BACKGROUND: The vision and mission statements of the Academy of Psychosomatic
      Medicine (APM) indicate that the APM should promote excellence in clinical care
      for patients with comorbid psychiatric and general medical conditions by seeking
      to influence research, public policy, and interdisciplinary education. OBJECTIVE:
      As the APM owns the journal, Psychosomatics, we sought to assess whether the
      APM's journal was fulfilling the vision and mission of its parent organization by
      reviewing the content of articles published in the journal to determine whether
      it sufficiently addresses the various clinical care knowledge areas it seeks to
      influence. METHODS: We categorized content in all review articles, case reports,
      and original research articles published in Psychosomatics in 2015 and 2016. Each
      article was assigned to as many categories that it covered. RESULTS: In the 163
      articles reviewed, the most frequently covered fund of knowledge area was
      psychiatric morbidity in medical populations (44.2%); among psychiatric
      disorders, mood disorders (22.1%), psychiatric disorders due to a general medical
      condition or toxic substance (21.5%), anxiety disorders (14.7%), and delirium
      (13.5) were the most frequently covered. Of the medical and surgical topics,
      neurology (19.6%), coping with chronic illness/psychological response to illness
      (17.8%), toxicology (11.7%), outpatient medicine (10.4%), and cardiology (9.8%)
      appeared most often. CONCLUSIONS: Psychosomatics appears to be successfully
      providing content relevant to the APM's vision and mission statements and to
      practitioners of psychosomatic medicine.

PMID- 28449829
TI  - Hypertension Canada's 2017 Guidelines for the Diagnosis, Assessment, Prevention,
      and Treatment of Pediatric Hypertension.
AB  - After the 2016 guidelines for blood pressure measurement, diagnosis, and
      investigation of pediatric hypertension, we now present evidence-based guidelines
      for the prevention and treatment of hypertension in children. These guidelines
      were developed by Hypertension Canada's Guideline Committee pediatric subgroup
      after thorough evaluation of the available literature. Included are 10 guidelines
      specifically addressing health behaviour management, indications for drug therapy
      in children with hypertension, choice of therapy for children with primary
      hypertension, and goals of therapy for children with hypertension. Although the
      pediatric literature is inherently limited by small numbers of participants,
      fewer trials, and a prolonged latency to the development of vascular outcomes,
      this report reflects the current and highest level of evidence and provides
      guidance for primary care practitioners on the management of pediatric
      hypertension. Studies of therapeutic lifestyle modifications in children are
      available to guide current management and more antihypertensive drugs have been
      studied in children since the Food and Drug Administration Modernization Act.
      Consistent with Hypertension Canada's guideline policy, diagnostic and
      therapeutic algorithm tools will be developed and the guidelines will be reviewed
      annually and updated according to new evidence.

PMID- 28449830
TI  - Barriers to Patient-Centered Care in Hypertension.

PMID- 28449828
TI  - Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention,
      and Treatment of Hypertension in Adults.
AB  - Hypertension Canada provides annually updated, evidence-based guidelines for the
      diagnosis, assessment, prevention, and treatment of hypertension. This year, we
      introduce 10 new guidelines. Three previous guidelines have been revised and 5
      have been removed. Previous age and frailty distinctions have been removed as
      considerations for when to initiate antihypertensive therapy. In the presence of
      macrovascular target organ damage, or in those with independent cardiovascular
      risk factors, antihypertensive therapy should be considered for all individuals
      with elevated average systolic nonautomated office blood pressure (non-AOBP)
      readings >= 140 mm Hg. For individuals with diastolic hypertension (with or
      without systolic hypertension), fixed-dose single-pill combinations are now
      recommended as an initial treatment option. Preference is given to pills
      containing an angiotensin-converting enzyme inhibitor or angiotensin receptor
      blocker in combination with either a calcium channel blocker or diuretic.
      Whenever a diuretic is selected as monotherapy, longer-acting agents are
      preferred. In patients with established ischemic heart disease, caution should be
      exercised in lowering diastolic non-AOBP to <= 60 mm Hg, especially in the
      presence of left ventricular hypertrophy. After a hemorrhagic stroke, in the
      first 24 hours, systolic non-AOBP lowering to < 140 mm Hg is not recommended.
      Finally, guidance is now provided for screening, initial diagnosis, assessment,
      and treatment of renovascular hypertension arising from fibromuscular dysplasia.
      The specific evidence and rationale underlying each of these guidelines are
      discussed.

PMID- 28449831
TI  - Aortic Vascular Calcification: Cholesterol Lowering Does Not Reduce Progression
      in Patients With Familial Hypercholesterolemia-or Does It?

PMID- 28449832
TI  - The Evolution of Targeted Interventions in the Age of Precision Medicine.

PMID- 28449833
TI  - Rational Medical Therapy Is the Key to Effective Cardiovascular Disease
      Prevention.
AB  - In an era in which medicine personalized on the basis of genotyping is being
      proposed, it is timely to recognize that existing therapies could be markedly
      improved if they were on the basis of more effective application of principles on
      the basis of available phenotyping. Blood pressure control, which is poor on a
      worldwide basis, is a major opportunity to reduce cardiovascular risk. There are
      many genetic variants that have a small effect on blood pressure, but specific
      therapies are not available for most of them. Individualized therapy for
      hypertension using plasma renin and aldosterone to identify the physiological
      drivers of hypertension might markedly improve blood pressure control. For
      patients with a high renin/high aldosterone phenotype, angiotensin receptor
      blockers are indicated. For those with a high aldosterone/low renin (primary
      aldosteronism) phenotype, aldosterone antagonists are best; for those with low
      renin/low aldosterone (a Liddle phenotype), amiloride is best. Effective
      antiplatelet therapy and anticoagulation, particularly with the new oral
      anticoagulants, can markedly reduce the risk of stroke. Metabolic B12 deficiency
      is very common, usually missed, and easily treated; B vitamins to lower
      homocysteine levels might be able to reduce the risk of stroke, particularly
      among elderly patients with atrial fibrillation. A particularly useful phenotype
      is carotid plaque burden. In high-risk patients, intensive lipid-lowering therapy
      aimed to prevent progression of carotid plaque can reduce the risk of stroke or
      myocardial infarction by > 80%. Available therapies, used more rationally on the
      basis of clinical pharmacology and phenotyping of our patients, could have a
      bigger effect than genome-based personalized medicine.

PMID- 28449834
TI  - Are Automated Blood Pressure Monitors Comparable to Ambulatory Blood Pressure
      Monitors? A Systematic Review and Meta-analysis.
AB  - Ambulatory blood pressure (BP) monitoring (ABPM) provides an accurate assessment
      of BP and cardiovascular risk. BpTRU (BpTRU Medical Devices Ltd, Coquitlam,
      British Columbia, Canada) and other automated oscillometric BP monitors (AOBPs)
      have been proposed to replace ABPM. A systematic review was carried out to
      determine the accuracy of AOBP measurement, compared with ABPM. A literature
      search was performed using MedLine, EMBASE and CINAHL databases until Oct 28,
      2016. We selected all studies that included intraindividual comparisons between
      AOBP monitoring and ABPM. Study selection, demographic characteristics, and BP
      values including details of BP measurement techniques were abstracted in
      duplicate. Quantitative synthesis was performed to report the weighted mean
      difference between systolic and diastolic BP measured using the 2 methods. From
      the 859 nonduplicate citations from the search, 19 full-text articles were
      selected for the systematic review. The median sample size was 226 (range, 17
      654). In the pooled analysis, the weighted mean difference between the 2 methods
      for systolic BP was -1.52 mm Hg (95% confidence interval [CI], -3.29 to 0.25 mm
      Hg; P = 0.09) and for diastolic BP was 0.33 mm Hg (95% CI, -0.97 to 1.64; P =
      0.62). The study-level difference in means for systolic BP ranged from -9.7 to 9
      mm Hg with significant heterogeneity (Cochran Q = 270; I2 = 93.3; P < 0.001) and
      for diastolic BP ranged from -4 to 6 mm Hg with significant heterogeneity
      (Cochran Q = 382; I2 = 95.3; P < 0.001). Because of the significant heterogeneity
      we believe that use of the AOBP should not replace awake ambulatory BP (ABPM) as
      the reference standard.

PMID- 28449835
TI  - The Gap Between Manual and Automated Office Blood Pressure Measurements Results
      at a Hypertension Clinic.
AB  - BACKGROUND: Blood pressure (BP) readings taken in clinics are often higher than
      BP readings taken in a research setting. Recent guidelines and clinical trials
      have highlighted the necessity of using automated office blood pressure (AOBP)
      devices and standardizing measurement procedures. The goal of the present study
      was to compare AOBP vs manual BP measurement in both research and clinical
      environments in which operators and devices were the same and measurement
      procedures were standardized and optimal. METHODS: Clinical manual BP and AOBP
      measurement estimates were gathered from a retrospective cohort of patients
      followed in a hypertension clinic. Research AOBP and manual BP measurement data
      were obtained from past research studies. Descriptive statistics and agreement
      analyses with Cohen kappa coefficients were developed. The AOBP/manual BP
      measurement gap between clinical and research follow-up was compared using an
      unpaired t test. RESULTS: Two hundred eighty-eight patients were included in the
      clinical cohort, and 195 patients contributed to research-grade BP data. All
      patients had hypertension. AOBP averages were lower than manual measurement
      averages in both clinical (-3.6 +/- 14.9 mm Hg / -3.0 +/- 8.8 mm Hg) and research
      (-2.7 +/- 10.0 / -2.4 +/- 6.3 mm Hg) environments. The gap between measurement
      methods did not differ between research and clinical data. Cohen kappa
      coefficient was lower in the clinical context because of greater variability and
      more time between BP measurements (5.5 +/- 2.9 months). CONCLUSIONS: Manual BP
      readings were slightly higher than AOBP estimates. The difference was not
      influenced by the real-world context of clinical practice. Office nonautomated BP
      measurements may still be valuable if measurement procedures are well
      standardized and performed by trained nurses.

PMID- 28449836
TI  - Aortic Calcification Progression in Heterozygote Familial Hypercholesterolemia.
AB  - BACKGROUND: Patients with homozygous and heterozygous familial
      hypercholesterolemia (HeFH) develop severe aortic calcifications in an age- and
      gene dosage-dependent manner. The purpose of this study was to determine the rate
      of progression of aortic calcification in patients with HeFH. METHODS: We
      performed thoracoabdominal computed tomography scans and quantified aortic
      calcium (AoCa) score in 16 HeFH patients, all with the null low-density
      lipoprotein (LDL) receptor DEL15Kb mutation. Patients (12 men, 4 women) were
      rescanned an average of 8.2 +/- 0.8 years after the first scan. RESULTS: Mean LDL
      cholesterol (LDL-C) during treatment was 2.53 mmol/L; all patients were receiving
      high-dose statin/ezetimibe; 5 of 16 were receiving evolocumab. Baseline LDL-C was
      7.6 +/- 1.3 mmol/L. Aortic calcifications increased in all patients in an
      exponential fashion with respect to age. Age was the strongest correlate of AoCa
      score. Cholesterol, LDL-C, or age * cholesterol did not correlate with AoCa score
      or its progression. Control patients (n = 31; 8 male, 23 female; mean age 61 +/-
      11 years) who underwent virtual colonoscopy were rescanned over the same period
      and showed an abdominal AoCa score of 1472 +/- 2489 compared with 7916 +/- 7060
      Agatston U (P < 0.001) in patients with HeFH during treatment (mean age, 60 +/-
      14 years). The rate of progression was 159 vs 312 Agatston U/y in control
      participants vs those with HeFH. CONCLUSIONS: HeFH patients exhibit accelerated
      aortic calcification that increases exponentially with age. LDL-C at baseline or
      during treatment seems to have little effect on the rate of progression of AoCa
      score. Strategies to prevent aortic calcifications with statins have not met with
      clinical success and novel approaches are required; statins might also contribute
      to the process of arterial calcification.

PMID- 28449837
TI  - Management Strategies for Statin-Associated Muscle Symptoms: How Useful Is Same
      Statin Rechallenge?
AB  - BACKGROUND: Statin-associated muscle symptoms (SAMS) are common. Rechallenge with
      the same statin (same-statin rechallenge) has recently been included as part of a
      proposed scoring index for diagnosing SAMS, but data regarding tolerability and
      efficacy of same-statin rechallenge, compared with other strategies, is minimal.
      In this study we evaluated the tolerability, percent change in low-density
      lipoprotein cholesterol (LDL-C), and proportion of patients achieving their LDL-C
      targets among 3 common management strategies-same-statin rechallenge, switching
      to a different statin (statin switch), and use of nonstatin medications only.
      METHODS: We performed a retrospective analysis of 118 patients referred to our
      tertiary care centre for management of SAMS, defined as development of muscle
      related symptoms with 2 or more statins. Baseline and last follow-up lipid
      parameters were documented. Patients were classified as tolerant of a strategy
      if, at their last follow-up, they remained on that strategy. RESULTS: After a
      median follow-up of 17 months, most (n = 79; 67%) patients were able to tolerate
      a statin. Tolerability was similar among the 3 treatment strategies (71% same
      statin rechallenge vs 53% statin switch vs 57% for nonstatin therapy only; P =
      0.11). Those in the same-statin rechallenge and statin switch groups achieved
      greater LDL-C reductions compared with those who only tolerated nonstatins (-38.8
      +/- 3.4% vs -36.4 +/- 2.9% vs -17.3 +/- 4.5%; P = 0.0007). A greater proportion
      of patients in the same-statin rechallenge group achieved their target LDL-C
      compared with those in the nonstatin therapy only group (50% vs 15%; odds ratio,
      6.8; 95% confidence interval, 1.5-40.7; P = 0.04). CONCLUSIONS: Among individuals
      with a history of SAMS, most will tolerate statin therapy. Same-statin
      rechallenge was highly tolerable and efficacious. Thus, same-statin rechallenge
      might warrant increased utilization.

PMID- 28449838
TI  - Electrocardiographic PR Interval Duration and Cardiovascular Risk: Results From
      the Copenhagen ECG Study.
AB  - BACKGROUND: Because of ambiguous reports in the literature, we aimed to
      investigate the association between PR interval and the risk of all-cause and
      cardiovascular death, heart failure, and pacemaker implantation, allowing for a
      nonlinear relationship. METHODS: We included 293,111 individuals, corresponding
      to one-third of the population in the greater region of Copenhagen. These
      individuals had a digital electrocardiogram recorded in a general practitioner's
      core facility from 2001-2011. Data on drug use, comorbidities, and outcomes were
      collected from Danish registries. We divided the population into 7 groups based
      on the population PR interval distribution. Cox models were used, with reference
      to a PR interval between 152 and 161 ms (40th to < 60th percentile). RESULTS:
      During follow-up, we identified 34,783 deaths from all causes, 9867
      cardiovascular deaths, 9526 cases of incident heart failure, and 1805 pacemaker
      implantations. A short PR interval (< 125 ms; hazard ratio [HR], 1.23; 95%
      confidence interval [CI], 1.08-1.41; P = 0.001) as well as a long PR interval (>
      200 ms; HR, 1.23; 95% CI, 1.14-1.32; P < 0.001) was associated with an increased
      risk of cardiovascular death after multivariable adjustment. A long PR interval
      conferred an increased risk of heart failure (> 200 ms; HR, 1.31; 95% CI, 1.22
      1.42; P < 0.001). An increasing PR interval conferred an increased risk of
      pacemaker implantation, in a dose-response manner, with the highest risk
      associated with a PR interval > 200 ms (HR, 3.49; 95% CI, 2.96-4.11; P < 0.001).
      CONCLUSIONS: PR interval was significantly associated with the risk of the
      adverse outcomes investigated. The nonlinear relationships, in combination with
      relatively weak associations, could contribute to previously reported conflicting
      results on the subject.

PMID- 28449839
TI  - Statin Prescriptions for High-Risk Patients Are Increased by Laboratory-Initiated
      Framingham Risk Scores: A Quality-Improvement Initiative.
AB  - Low rates of cardiovascular preventive therapy with statin medications is a
      significant public health problem in Canada. There is a pressing need for public
      health interventions to increase the use of statin medications, especially among
      high-risk patients. In this article, we present the results of a quality
      assurance pilot program to provide laboratory-reported Framingham Risk Score
      (FRS) to physicians. This work was performed in a mixed urban and rural setting
      in southern Alberta. We provided FRSs and, for high-risk patients, statin
      treatment recommendations in conjunction with laboratory lipid panel requests.
      Adhesive labels were supplied to primary care physicians, and space was provided
      for information necessary for the calculation of the FRS by a laboratory
      information system. In total, 16 physicians from 4 different clinics participated
      in the pilot program. Data were collected from October 25, 2014-November 5, 2015,
      during which time 1266 patients had FRSs from the laboratory. Three hundred
      twenty-four individuals were identified as high risk for coronary heart disease
      (>= 20% 10-year risk) and received a recommendation for treatment with a statin
      medication in the laboratory result report. These individuals had a 26% relative
      and a 6.4% absolute increase in statin prescriptions compared with before the
      pilot program. The laboratory-based provision of FRSs with statin treatment
      recommendations for high-risk individuals has the potential to significantly
      increase the use of statin drugs.

PMID- 28449840
TI  - Collectively Operated Fellow-Initiated Research as a Novel Teaching Model to
      Bolster Interest and Increase Proficiency in Academic Research.
AB  - Research is a core aspect of training in academic medicine, but fellows face many
      challenges thwarting their ability to perform clinically meaningful projects. The
      concept of a multicentre clinical trial collectively operated by fellows, and
      integrated longitudinally into training, has never been described. In this
      article, the authors expose the key principles of Collectively Operated Fellow
      Initiated Research (COFIR) that they put in place. The aim of COFIR is to
      introduce a cohort of fellows to the career of clinician-scientists by conducting
      a longitudinal research project integrated into the curriculum of their clinical
      fellowship at a level they would not have access to as single individuals. First,
      fellows must formulate the research hypothesis to generate a patient-oriented
      research idea that resonates with a large group of trainees. Second, fellows must
      be actively involved in the multifaceted aspects of research under the mentorship
      of clinical scientists. Third, fellows must document and disseminate the newly
      acquired methodological know-how. Finally, fellows must put the safety of
      patients above any other consideration. Examples of how these principles were
      applied in a research project are provided in this article; it represents a call
      to action for fellows to collectively contribute to the production of significant
      medical research.

PMID- 28449841
TI  - Multimodal Images of a Large Spontaneous Aortic Root Pseudoaneurysm With Right
      Atrium and Tricuspid Annulus Compression.

PMID- 28449842
TI  - Critical issues in the historical and contemporary development of forensic
      anthropology in Australia: An international comparison.
AB  - The aim of this brief critical qualitative analysis is to examine the development
      of forensic anthropology in Australia, at a time of significant change in the
      discipline. It will briefly summarise its historical establishment, making
      comparative reference to other regions-particularly the United Kingdom and United
      States, and the influence of the Bali Bombings of 2002, Indian Ocean earthquake
      and tsunami of 2004 and Black Saturday Bushfires of 2009. The analysis goes on to
      consider key factors in research in forensic anthropology in the United States,
      and the development of standards and regulation in the US and UK. The
      significance of research in post-mortem diagenesis in Brazil-a country sharing
      aspects of climate, soil types and demography with Australia-is also considered,
      as well as the significance of patterns of casework encountered in Australia
      compared with those of other jurisdictions. While forensic anthropology as a
      discipline has grown remarkably in recent years, this analysis suggests that
      research and training tailored to the specific pattern of casework encountered in
      Australia is now essential to support the development of national standards in
      science, education, and professional regulation. The significance of the
      establishment of the first taphonomy research facility outside of the US-the
      Australian Facility for Taphonomic Experimental Research-is briefly considered
      with reference to what this facility may offer to the development of forensic
      anthropology in Australia.

PMID- 28449843
TI  - [Short-term follow-up after acute COPD exacerbation].

PMID- 28449844
TI  - Relationship between vancomycin exposure and outcomes among patients with MRSA
      bloodstream infections with vancomycin Etest(r) MIC values of 1.5mg/L: A pilot
      study.
AB  - Data suggest that vancomycin is less effective for methicillin-resistant
      Staphylococcus aureus (MRSA) bloodstream infection (BSI) with vancomycin Etest(r)
      MIC (MICEtest) >=1.5 mg/L. No published studies have evaluated the relationship
      between vancomycin exposure and outcomes among patients with MRSA BSIs vancomycin
      MICEtest >=1.5 mg/L. This study was a retrospective cohort of 71 hospitalized,
      adult, non-dialysis patients with MRSA BSIs treated with vancomycin. All but
      three patients had a vancomycin MICEtest of 1.5 mg/L. Achievement of CART-derived
      AUC24-48h of at least 550 mg*h/L (AUC24-48h/MIC of 366 mg*h/L) was associated
      with a lower incidence of treatment failure. In multivariate analyses, the risk
      ratio was 0.45 for the CART-derived AUC24-48h threshold, indicating that
      achievement of the CART-derived AUC24-48h threshold of 550 was associated with a
      2-fold decrease in treatment failure. These findings suggest a potential
      association between vancomycin exposure and outcomes in patients with MRSA BSIs
      with MICEtest >=1.5 mg/L. As this study was retrospective, these findings provide
      the basis for a future large-scale, multi-center prospective study.

PMID- 28449845
TI  - Comparison of Short-Term Outcomes After Total Hip Arthroplasty Between an
      Orthopedic Specialty Hospital and General Hospital.
AB  - BACKGROUND: The purpose of this study is to compare perioperative outcomes for
      total hip arthroplasty (THA) at an orthopedic specialty hospital (OSH) and a
      general hospital (GH). METHODS: A retrospective study of all primary THAs was
      performed at an OSH and GH in 2014. A cohort of GH patients was manually matched
      to the OSH by clinical and demographic variables blinded to outcome. These
      matched groups were then unblinded and compared by length of stay (LOS), 90-day
      readmissions, mortality, reoperations, and inpatient rehabilitation utilization.
      RESULTS: The 329 THAs at the OSH were matched with 329 THAs at the GH. Average
      LOS for THA at the OSH was 1.10 +/- 0.51 days compared with 1.27 +/- 0.93 (P =
      .004) at the GH. There were 2 OSH readmissions vs 5 GH readmissions (P = .25).
      There were 3 OSH reoperations vs 4 GH reoperations (P = .70). There were no
      mortalities. Three OSH patients used inpatient rehabilitation vs 13 GH patients
      (P = .011). When GH outlier and rehabilitation patients were excluded, the
      difference in LOS was not significant (1.08 +/- 0.47 vs 1.13 +/- 0.55 days; t =
      1.331; P = .184). Two OSH patients required transfer to a GH postoperatively
      (angina and gastrointestinal bleed). CONCLUSION: This study found that
      perioperative outcomes for THA were equally good at the OSH and GH.
      Rehabilitation utilization was higher at the GH. The LOS at both facilities was
      lower than the national average of 2.9 days. When rehabilitation patients and
      outliers were excluded, there was no significant difference in LOS between the
      two.

PMID- 28449847
TI  - Loss of WDFY3 ameliorates severity of serum transfer-induced arthritis
      independently of autophagy.
AB  - WDFY3 is a master regulator of selective autophagy that we recently showed to
      interact with TRAF6 and augment RANKL-induced osteoclastogenesis in vitro and in
      vivo via the NF-kappaB pathway. Since the NF-kappaB pathway plays a major role in
      inflammation herein, we investigate the role of WDFY3 in an arthritis animal
      model. Our data show that WDFY3 conditional knockout mice (Wdfy3loxP/loxP-LysM
      Cre+) were protected in the K/BxN serum transfer-induced arthritis animal model.
      These effects were independent of alterations in starvation-induced autophagy as
      evidenced by Western blot analysis of the autophagy marker LC3, autophagosome
      formation in osteoclast precursors and lysosome formation in osteoclasts derived
      from WDFY3-cKO mice compared to controls. Moreover, we demonstrate by
      immunofluorescence and co-immunoprecipitation that WDFY3 interacts with SQSTM1 in
      macrophages and osteoclasts. Collectively, our data suggest that loss of WDFY3 in
      myeloid cells leads to reduced severity of inflammatory arthritis independently
      of WDFY3 function in starvation-induced autophagy.

PMID- 28449848
TI  - Adverse Local Tissue Responses to Failed Temporomandibular Joint Implants.
AB  - PURPOSE: The purpose of this study was to determine whether failed alloplastic
      temporomandibular joint replacement (TMJR) devices can elicit the aseptic
      lymphocyte-dominated vasculitis-associated lesion (ALVAL) reaction seen in some
      patients with metal-on-metal hip arthroplasties. MATERIALS AND METHODS: This
      study involved analysis of paraffin-embedded sections of peri-implant tissue from
      failed TMJ implant cases obtained from 3 independent sources. Hematoxylin and
      eosin staining, conventional and polarized light microscopy, back-scattered
      electron imaging, and energy-dispersive x-ray analysis were used.
      Immunohistochemical methods were used to identify T and B lymphocytes and
      macrophages. RESULTS: The total TMJR device specimens showed primary macrophage
      and lymphocytic responses similar to responses reported previously for failed
      total hip implants, including ALVAL. No chronic or acute inflammation was
      apparent in the failed hemiarthroplasty TMJR cases. CONCLUSION: In this limited
      preliminary study, the local tissue responses to the failed TMJR implants showed
      similar primary macrophage and lymphocyte responses to previously reported failed
      metal-on-metal and metal-on-polyethylene orthopedic total joint replacement
      devices. No such local inflammatory responses were seen with the failed TMJR
      hemiarthroplasty devices.

PMID- 28449849
TI  - Alzheimer's Disease in Primary Care: The Significance of Early Detection,
      Diagnosis, and Intervention.
AB  - The field of Alzheimer's disease (AD) is undergoing a profound and rapid change:
      clinical trials have been redesigned to focus on individuals in the earliest
      stages of the disease and are including more sensitive measurement tools to
      better capture changes in cognition and other outcomes. (Online access:
      http://courses.elseviercme.com/adwebcast/674http://courses.elseviercme.com/alzhei
      er/593e). Trial participants undergo PET imaging for amyloid load as a hallmark
      for dementia, as well as genetic testing to determine likelihood of disease
      progression and response to therapeutic intervention. Large national and
      international registries have been established to capture those at risk and to
      follow their development of cognitive changes longitudinally. Understanding that
      the disease process starts at least a decade or more before the onset of symptoms
      has prompted the development of therapeutic interventions acting very early in
      the disease cascade. For all these reasons, recognizing and diagnosing AD early
      offers affected individuals and their caregivers the best chance for care
      planning, access to available symptomatic treatment and community resources, as
      well as involvement with clinical trials and access to new therapies when they
      become available. Primary care clinicians play a pivotal role in the early
      recognition of cognitive impairment in their patients.

PMID- 28449851
TI  - Acute compartment syndrome.
AB  - Acute compartment syndrome is a well-known complication of tibial fractures, yet
      it remains difficult to diagnose and the only effective treatment is surgical
      fasciotomy. Delayed fasciotomy is the most important factor contributing to poor
      outcomes, and as a result, treatment is biased towards performing early
      fasciotomy. Current diagnosis of ACS is based on clinical findings and
      intramuscular pressure (IMP) measurement, and is targeted at identifying safe
      thresholds for when fasciotomy can be avoided. Since clinical findings are
      variable and difficult to quantify, measurement of IMP - ideally continuously -
      is the cornerstone of surgical decision - making. Numerous investigators are
      searching for less invasive and more direct measurements of tissue ischemia,
      including measurement of oxygenation, biomarkers, and even neurologic monitoring.
      This article provides a brief but thorough review of the current state of the art
      in compartment syndrome diagnosis and treatment.

PMID- 28449852
TI  - Radiation exposure during intramedullary nailing.
AB  - Surgeons should aim to keep radiation exposure "As Low As Reasonably Achievable
      (ALARA)" during intramedullary nailing and other minimally invasive surgical
      procedures. This requires understanding the principles of ionizing radiation and
      methods for minimizing exposure risk. The main source of radiation exposure to
      surgical personnel during fluoroscopy is from scattered radiation. Since
      radiation scatter is mainly directed towards the fluoroscopy source, the best
      configuration during surgery to reduce radiation dose to the surgeon is to
      position the fluoroscopic source below the operating room table and the image
      collector above the table. During cross table imaging, the surgeon should stand
      on the side with the image collector to minimize their exposure to radiation
      scatter. To reduce scattered radiation the patient must be placed as close to the
      image collector and as far away from the x-ray tube as possible. Standing farther
      away from the patient can exponentially reduce radiation exposure. The hands
      usually have the greatest dose exposure to radiation during surgical procedures,
      but they are far less radiosensitive than the eyes or thyroid. To minimize
      exposure to the hands, a surgeon should use the hands-off technique taking
      fluoroscopic images only when his or her hands are farthest from the radiographic
      field. Lead gowns, lead thyroid shields, and lead glasses, further reduces an
      individual's exposure to radiation.

PMID- 28449850
TI  - Migration pathways of sacral neural crest during development of lower urogenital
      tract innervation.
AB  - The migration and fate of cranial and vagal neural crest-derived progenitor cells
      (NCPCs) have been extensively studied; however, much less is known about sacral
      NCPCs particularly in regard to their distribution in the urogenital system. To
      construct a spatiotemporal map of NCPC migration pathways into the developing
      lower urinary tract, we utilized the Sox10-H2BVenus transgene to visualize NCPCs
      expressing Sox10. Our aim was to define the relationship of Sox10-expressing
      NCPCs relative to bladder innervation, smooth muscle differentiation, and
      vascularization through fetal development into adulthood. Sacral NCPC migration
      is a highly regimented, specifically timed process, with several potential
      regulatory mileposts. Neuronal differentiation occurs concomitantly with sacral
      NCPC migration, and neuronal cell bodies are present even before the pelvic
      ganglia coalesce. Sacral NCPCs reside within the pelvic ganglia anlagen through
      13.5 days post coitum (dpc), after which they begin streaming into the bladder
      body in progressive waves. Smooth muscle differentiation and vascularization of
      the bladder initiate prior to innervation and appear to be independent processes.
      In adult bladder, the majority of Sox10+ cells express the glial marker S100beta,
      consistent with Sox10 being a glial marker in other tissues. However, rare Sox10+
      NCPCs are seen in close proximity to blood vessels and not all are S100beta+,
      suggesting either glial heterogeneity or a potential nonglial role for Sox10+
      cells along vasculature. Taken together, the developmental atlas of Sox10+ NCPC
      migration and distribution profile of these cells in adult bladder provided here
      will serve as a roadmap for future investigation in mouse models of lower urinary
      tract dysfunction.

PMID- 28449853
TI  - Malalignment in intramedullary nailing. How to achieve and to maintain correct
      reduction?
AB  - Intramedullary nailing has become the standard for the treatment of long bones
      diaphyseal fractures. Modern techniques of locking have further enlarged the
      primary indications to more proximal and distal fractures relying upon a former
      correct alignment. Nevertheless, residual deformities are not rare as once the
      nail has left the narrow diaphyseal canal and comes into the wider metaphysis, it
      may follow an unwished trajectory. There is also a chance for malreduction in
      diapyhseal fractures. The more complex the fracture is, the more difficult its
      reduction, not only for the alignment of the proximal or the distal part of bone
      in relation to the diaphysis, but also correct rotation and length. In this
      paper, we analyze recommended techniques to achieve accurate bone fracture
      reduction, to avoid post-operative deformities combined with correct implant
      insertion.

PMID- 28449854
TI  - Complications of intramedullary nailing-Evolution of treatment.
AB  - Intramedullary nailing of diaphyseal long bone fractures is a standard procedure
      in today's trauma and orthopedic surgery due to the numerous advantages (e.g.
      minimal invasive, limited soft tissue damage, load stability). In the last decade
      indications have been extended to the metaphyseal region. This was associated
      with problems and complications due to the reduced bone-implant interface. The
      changed anatomical conditions lead to decreased implant anchorage. Newly
      developed locking solutions overcome most of these problems. First, the number
      and also the orientation of the locking screws were adapted to allow a
      multiplanar locking. This results in increased implant anchorage in the soft
      metaphyseal bone, thus construct stability significantly improved. Additional
      options like angular stable locking have been introduced and furthermore enhanced
      construct stability especially in poor bone stock. As a perspective locking screw
      augmentation shows promising results in first biomechanical testing.

PMID- 28449856
TI  - Intramedullary nailing-Evolution of treatment.

PMID- 28449855
TI  - Intramedullary nail fixation of non-traditional fractures: Clavicle, forearm,
      fibula.
AB  - Locked intramedullary fixation is a well-established technique for managing long
      bone fractures. While intramedullary nail fixation of diaphyseal fractures in the
      femur, tibia, and humerus is well established, the same is not true for other
      fractures. Surgical fixations of clavicle, forearm and ankle are traditionally
      treated with plate and screw fixation. In some cases, fixation with an
      intramedullary device is possible, and may be advantageous. However, there is
      however a concern regarding a lack of rotational stability and fracture
      shortening. While new generation of locked intramedullary devices for fractures
      of clavicle, forearm and fibula are recently available, the outcomes are not as
      reliable as fixation with plates and screws. Further research in this area is
      warranted with high quality comparative studies, to investigate the outcomes and
      indication of these fractures treated with intramedullary nail devices compared
      to intramedullary nail fixation.

PMID- 28449857
TI  - Management of traumatic bone defects: Metaphyseal versus diaphyseal defects.
AB  - Although bone defects after trauma appear in different locations and forms, many
      clinicians have adopted a single strategy to deal with any defect. In this
      overview, a distinction is made between metaphyseal, or cancellous defects, and
      diaphyseal, or cortical defects. The treatment goals and background of these two
      types of defects are discussed in order to describe the difference in strategy
      and hence the difference in treatment method.

PMID- 28449858
TI  - Computer-assisted surgery: The use of stored intraoperative images for accurate
      restoration of femoral length and rotational alignment after fracture.
AB  - Most femoral fractures are now managed with minimally invasive internal fixation.
      In the absence of formal exposure of the fracture lines, these procedures make
      heavy use of C-arm fluoroscopy to allow both fracture reduction and placement of
      implants, at the expense of measurable radiation exposure to both patient and
      surgeon. Although this technology has been commercially available for over a
      decade, it has not yet been widely accepted by the Orthopaedic community.

PMID- 28449859
TI  - The role of the intramedullary implant in limb lengthening.
AB  - Limb lengthening is now an accepted practice in orthopaedic surgery. The
      principles of distraction osteogenesis have become well established with the use
      of external fixators, utilizing both monolateral and ring fixators. Corticotomy
      technique, frame stability, lengthening rate and rhythm all contribute to the
      formation of bone regenerate and tissues. Complications are however common
      including pin-site infection, soft tissue tethering from the pins and wires
      resulting in pain, regenerate deformity from soft tissue forces or fracture
      following frame removal and patient intolerance of the frames during treatment.
      Surgical techniques have changed to try and minimise these complications. The use
      of intramedullary nails have been used in conjunction with an external fixator or
      inserted after lengthening has been achieved, to reduce fixator time and prevent
      regenerate deformity. Implant innovation has led to the production of
      intramedullary lengthening nails. The initial devices used ratchet mechanisms
      with rotation of the bone fragments to achieve lengthening (Bliskunov, Albizzia
      and ISKD). More accurate control of lengthening and a reduction in pain,
      resulting from the manual rotation of the leg required to achieve the ratchet
      progression, was achieved by the use of a transcutaneous electrical conduit
      powered by external high frequency electrical energy (Fitbone). The most recent
      implant uses an external remote controller which contains two neodymium magnets.
      These are placed over the nail on the skin and rotate which in turn rotates a
      third magnet within the intramedullary nail (Precice). This magnet rotation is
      converted by a motor to extend or retract the extendible rod. There are multiple
      nail sizes and lengths available, and early results have shown accurate control
      with few complications. With such promising outcomes the use of this lengthening
      intramedullary nail is now recommended as the implant of choice in femoral
      lengthening. This article is an historical account of the intramedullary device
      and the impact on limb lengthening.

PMID- 28449860
TI  - Timing of definitive fixation of major long bone fractures: Can fat embolism
      syndrome be prevented?
AB  - Fat embolism is common in patients with major fractures, but leads to devastating
      consequences, named fat embolism syndrome (FES) in some. Despite advances in
      treatment strategies regarding the timing of definitive fixation of major
      fractures, FES still occurs in patients. In this overview, current literature is
      reviewed and optimal treatment strategies for patients with multiple traumatic
      injuries, including major fractures, are discussed. Considering the
      multifactorial etiology of FES, including mechanical and biochemical pathways,
      FES cannot be prevented in all patients. However, screening for symptoms of FES
      should be standard in the pre-operative work-up of these patients, prior to
      definitive fixation of major fractures.

PMID- 28449861
TI  - The effects of irradiation dose and storage time following treatment on the
      viscoelastic properties of decellularised porcine super flexor tendon.
AB  - Decellularised porcine super flexor tendon (pSFT) offers a promising solution to
      the replacement of damaged anterior cruciate ligament. It is desirable to package
      and terminally sterilise the acellular grafts to eliminate any possible harmful
      pathogens. However, irradiation techniques can damage the collagen structure and
      consequently reduce the mechanical properties. The aims of this study were to
      investigate the effects of irradiation sterilisation of varying dosages on the
      viscoelastic properties of the decellularised pSFT. Decellularised pSFT tendons
      were subjected to irradiation sterilisation using either 30kGygamma, 55kGygamma,
      34kGy E-beam, 15kGygamma, 15kGy E-beam and (15+15) kGy E-beam (fractionated
      dose). Specimens then underwent stress relaxation testing at 0 and 12months post
      sterilisation to determine whether any effect on the viscoelastic properties was
      progressive. Significant differences were found which demonstrated that all
      irradiation treatments had an effect on the time-independent and time-dependent
      viscoelastic properties of irradiated tendons compared to peracetic acid only
      treated controls. No significant differences were found between the irradiated
      groups and no significant differences were found between groups at 0 and
      12months. These results indicate the decellularised pSFT graft has a stable shelf
      life.

PMID- 28449862
TI  - Innate lymphoid cells in atherosclerosis.
AB  - The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid
      tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have
      been shown to have important roles in protection against microbes, regulation of
      inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-gamma
      upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to
      IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23
      or IL-1. Although few studies have directly investigated the role for ILCs in
      atherosclerosis, several studies have investigated transcription factors and
      cytokines shared by ILCs and T helper cells. In this review we summarize our
      current understanding of the role of ILC in atherosclerosis and discuss future
      directions.

PMID- 28449863
TI  - Attitudes of dentists toward denture adhesives: A questionnaire survey in Greece.
AB  - STATEMENT OF PROBLEM: The attitudes of dental professionals toward denture
      adhesives (DAs) require further investigation. PURPOSE: The purpose of this
      survey was to assess the attitudes of dentists in Greece toward DAs and the
      possible effects of sex, age, training, and awareness level on these attitudes.
      MATERIAL AND METHODS: An 18-item questionnaire in the Greek language concerning
      the use of DAs by dentists in the metropolitan area of Athens, Greece was
      distributed on line. Its URL address was emailed to 793 randomly chosen dentists
      in the area, 438 of whom filled out and submitted a valid questionnaire (55.2%
      response rate). Data for each item were statistically analyzed for their
      associations with sex, age, training, and awareness level by the chi-square test
      for independence (alpha=.05). RESULTS: The results showed that 61.5% of general
      practitioners and 49% of specialist prosthodontists recommend the use of DAs.
      Their continuous use was recommended most frequently (46.9%), mainly in the cream
      form (93.8%). Their use was recommended not only for patients wearing older
      dentures (60.2%) but also for patients with newly fabricated ones (61.9%) to
      assist their adaptation to dentures (42.2%). Associations were found between a
      few only items and sex (Q07, Q11a,b), age (Q13), training (Q11q,b), and awareness
      level (Q11a,b,d,e) (P<.05). CONCLUSIONS: This survey shows that in the
      metropolitan area of Athens, Greece, a significant proportion of dentists (60.3%)
      recommend the use of DAs and do so more often as a continuous regimen for both
      existing and new denture wearers. Sex, age, training, and awareness level proved
      to be factors affecting only a few dentists' attitudes.

PMID- 28449864
TI  - Generation and evaluation of 3D digital casts of maxillary defects based on
      multisource data registration: A pilot clinical study.
AB  - STATEMENT OF PROBLEM: Digital techniques are not clinically applied for 1-piece
      maxillary prostheses containing an obturator and removable partial denture
      retained by the remaining teeth because of the difficulty in obtaining
      sufficiently accurate 3-dimensional (3D) images. PURPOSE: The purpose of this
      pilot clinical study was to generate 3D digital casts of maxillary defects,
      including the defective region and the maxillary dentition, based on multisource
      data registration and to evaluate their effectiveness. MATERIAL AND METHODS:
      Twelve participants with maxillary defects were selected. The maxillofacial
      region was scanned with spiral computer tomography (CT), and the maxillary arch
      and palate were scanned using an intraoral optical scanner. The 3D images from
      the CT and intraoral scanner were registered and merged to form a 3D digital cast
      of the maxillary defect containing the anatomic structures needed for the
      maxillary prosthesis. This included the defect cavity, maxillary dentition, and
      palate. Traditional silicone impressions were also made, and stone casts were
      poured. The accuracy of the digital cast in comparison with that of the stone
      cast was evaluated by measuring the distance between 4 anatomic landmarks.
      Differences and consistencies were assessed using paired Student t tests and the
      intraclass correlation coefficient (ICC). In 3 participants, physical resin casts
      were produced by rapid prototyping from digital casts. Based on the resin casts,
      maxillary prostheses were fabricated by using conventional methods and then
      evaluated in the participants to assess the clinical applicability of the digital
      casts. RESULTS: Digital casts of the maxillary defects were generated and
      contained all the anatomic details needed for the maxillary prosthesis. Comparing
      the digital and stone casts, a paired Student t test indicated that differences
      in the linear distances between landmarks were not statistically significant
      (P>.05). High ICC values (0.977 to 0.998) for the interlandmark distances further
      indicated the high degree of consistency between the digital and stone casts. The
      maxillary prostheses showed good clinical effectiveness, indicating that the
      corresponding digital casts met the requirements for clinical application.
      CONCLUSIONS: Based on multisource data from spiral CT and the intraoral scanner,
      3D digital casts of maxillary defects were generated using the registration
      technique. These casts were consistent with conventional stone casts in terms of
      accuracy and were suitable for clinical use.

PMID- 28449865
TI  - Flexible feeding obturator for early intervention in infants with Pierre Robin
      sequence.
AB  - Pierre Robin sequence presents with distinct features of retrognathia and
      glossoptosis with or without cleft palate, which results in potentially serious,
      life-threatening respiratory obstruction and feeding complications. A
      multidisciplinary approach is required to manage such complex features. This
      article describes a novel technique for managing Pierre Robin sequence using a
      flexible feeding obturator. This custom-made intraoral appliance overcomes
      numerous problems associated with the available feeding obturators and helps
      infants and parents cope with a variety of difficulties.

PMID- 28449866
TI  - Digital scanning to aid guiding plane and rest seat preparations for removable
      partial dentures.
AB  - This article describes the use of a digital intraoral scanner to aid clinicians
      making rest seat and guiding plane preparations, simplifying the procedure and
      reducing the time needed to analyze the abutment modifications. No additional
      equipment is required other than a diagnostic cast and a digital scanner with
      preparation comparison software.

PMID- 28449867
TI  - Cost-effectiveness of Ingenol Mebutate Gel for the Treatment of Actinic Keratosis
      in Greece.
AB  - PURPOSE: The present study aimed to perform a cost-effectiveness analysis of
      ingenol mebutate (IM) versus other topical alternatives for the treatment of
      actinic keratosis (AK). METHODS: The analysis used a decision tree to calculate
      the clinical effects and costs of AK first-line treatments, IM (2-3 days),
      diclofenac 3% (for 8 or 12 weeks), imiquimod 5% (for 4 or 8 weeks), during a 24
      month horizon, using discrete intervals of 6 months. A hypothetical cohort of
      immunocompetent adult patients with clinically confirmed AK on the face and scalp
      or trunk and extremities was considered. Clinical data on the relative efficacy
      were obtained from a network meta-analysis. Inputs concerning resource use
      derived from an expert panel. All costs were calculated from a Greek third-party
      payer perspective. FINDINGS: IM 0.015% and 0.05% were both cost-effective
      compared with diclofenac and below a willingness-to-pay threshold of ?30,000 per
      quality-adjusted life-year (QALY) (?199 and ?167 per QALY, respectively).
      Comparing IM on the face and scalp AK lesions for 3 days versus imiquimod for 4
      weeks resulted in an incremental cost-effectiveness ratio of ?10,868 per QALY. IM
      was dominant during the 8-week imiquimod period. IM use on the trunk and
      extremities compared with diclofenac (8 or 12 weeks) led to incremental cost
      effectiveness ratios estimated at ?1584 and ?1316 per QALY accordingly. Results
      remained robust to deterministic and probabilistic sensitivity analyses.
      IMPLICATIONS: From a social insurance perspective in Greece, IM 0.015% and IM
      0.05% could be the most cost-effective first-line topical field treatment options
      in all cases for AK treatment.

PMID- 28449869
TI  - Caffeic acid phenethyl ester attenuates pathological cardiac hypertrophy by
      regulation of MEK/ERK signaling pathway in vivo and vitro.
AB  - AIM: To explore the effects of caffeic acid phenethyl ester (CAPE) on cardiac
      hypertrophy induced by pressure overload. MAIN METHODS: Male wild-type C57 mice,
      aged 8-10weeks, were used for aortic banding (AB) to induce cardiac hypertrophy.
      CAPE or (resveratrol) RS was administered from the 3rd day after AB surgery for
      6weeks. Echocardiography and hemodynamic analysis were performed to estimate
      cardiac function. Mice hearts were collected for H&E and PSR staining. Western
      blot analysis and quantitative PCR were performed for to investigate molecular
      mechanism. We further confirmed our findings in H9c2 cardiac fibroblasts treated
      with PE or CAPE. KEY FINDINGS: CAPE protected against cardiac hypertrophy induced
      by pressure overload, as evidenced by inhibition of cardiac hypertrophy and
      improvement in mouse cardiac function. The effect of CAPE on cardiac hypertrophy
      was mediated via inhibition of the MEK/ERK and TGFbeta-Smad signaling pathways.
      We also demonstrated that CAPE protected H9c2 cells from PE-induced hypertrophy
      in vitro via a similar molecular mechanism as seen in the mouse heart. Finally,
      CAPE seemed to be as effective as RS for treatment of pressure overload induced
      mouse cardiac hypertrophy. SIGNIFICANCE: Our results suggest that CAPE may play
      an important role in the regulation of cardiac hypertrophy induced by pressure
      overload via negative regulation of the MEK/ERK and TGFbeta/Smad signaling
      pathways. These results indicate that CAPE could potentially be used for
      treatment of cardiac hypertrophy.

PMID- 28449868
TI  - Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years.
AB  - PURPOSE: Vitamin D is a potent immunomodulator capable of dampening inflammatory
      signals in several cell types involved in the asthmatic response. Its deficiency
      has been associated with increased inflammation, exacerbations, and overall poor
      outcomes in patients with asthma. Given the increase in the prevalence of asthma
      over the past few decades, there has been enormous interest in the use of vitamin
      D supplementation as a potential therapeutic option. Here, we critically reviewed
      the most recent findings from in vitro studies, animal models, and clinical
      trials regarding the role of vitamin D in treating bronchial asthma. METHODS:
      Using the key terms [Vitamin D, asthma, clinical trials, in vivo and in vitro
      studies], the [PubMed, Google Scholar] databases were searched for [clinical
      trials, original research articles, meta-analyses, and reviews], English-language
      articles published from [2012] to the present. Articles that were [Articles that
      did not meet these criteria were excluded] excluded from the analysis. FINDINGS:
      Several studies have found that low serum levels of vitamin D (< 20 ng/mL) are
      associated with increased exacerbations, increased airway inflammation, decreased
      lung function, and poor prognosis in asthmatic patients. Results from in vitro
      and in vivo studies in animals and humans have suggested that supplementation
      with vitamin D may ameliorate several hallmark features of asthma. However, the
      findings obtained from clinical trials are controversial and do not unequivocally
      support a beneficial role of vitamin D in asthma. Largely, interventional studies
      in children, pregnant women, and adults have primarily found little to no effect
      of vitamin D supplementation on improved asthma symptoms, onset, or progression
      of the disease. This could be related to the severity of the disease process and
      other confounding factors. IMPLICATIONS: Despite the conflicting data obtained
      from clinical trials, vitamin D deficiency may influence the inflammatory
      response in the airways. Further studies are needed to determine the exact
      mechanisms by which vitamin D supplementation may induce antiinflammatory
      effects.

PMID- 28449870
TI  - The effects of calorie-matched high-fat diet consumption on spontaneous physical
      activity and development of obesity.
AB  - AIMS: To characterize the effects of a calorie matched high-fat diet (HFD) on
      spontaneous physical activity (SPA), body weight, inflammatory status and
      expression of genes related to energy homeostasis in hypothalamus of mice. MAIN
      METHODS: C57Bl/6 mice (n=5 per group) were fed a control diet (16.5% calories
      from fat) - control group (C), or a calorie matched HFD (60% calories from fat).
      We evaluated, periodically, body weight and SPA by infrared beam sensors and, at
      the end of the 12th week, we verified blood glucose levels, fat pads weight,
      plasma insulin, TNF-alpha and IL-6 by ELISA and the hypothalamic expression of 84
      genes related to energy homeostasis, by quantitative real-time PCR array. KEY
      FINDINGS: Isocaloric HFD reduced SPA already in the first 48h and SPA was kept
      lower in the HFD compared to C throughout. These changes resulted in an increase
      in body weight, adiposity, TNF-alpha and IL-6, blood glucose and hyperinsulinemia
      in the HFD group when compared to the C group. Expression of the Agrp, Bdnf,
      Adra2b and Pyy genes were altered in the hypothalamus of HFD-fed mice,
      highlighting the downregulation of Bdnf, key regulator of energy homeostasis.
      SIGNIFICANCE: Dietary macronutrient distribution plays an important part in
      energy homeostasis that goes beyond its energy content. Despite calorie-matched,
      the HFD led to increased body weight and adiposity due to decreased SPA,
      highlighting the key role of SPA on energy balance. The changes in hypothalamic
      gene expression seem to underlie the reduction in SPA caused by HFD.

PMID- 28449871
TI  - SIRT3 and mitochondrial metabolism in neurodegenerative diseases.
AB  - The NAD+-dependent deacetylase protein Sirtuin 3 (SIRT3) is emerging among the
      factors playing a key role in the regulation of mitochondrial function and in the
      prevention of oxidative stress. This deacetylase activates protein substrates
      directly involved in the production and detoxification of ROS, such as superoxide
      dismutase 2 and catalase, but also enzymes in the lipid beta-oxidation pathway.
      In this paper we review existing evidence on the role of SIRT3 in
      neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and
      Huntington disease, including data from new experiments in a model for
      amyotrophic lateral sclerosis linked to mutations in superoxide dismutase 1.
      Specifically, we report that expression of the mitochondrial isoform of SIRT3 is
      altered in muscle from the G93A-SOD1 mice during progression of disease; this
      alteration influences mitochondrial metabolism, which may be relevant for the
      well known energetic alterations taking place in ALS patients. These data
      reinforce the concept that SIRT3 may be a relevant therapeutic target is ALS as
      well as in other neurodegenerative diseases.

PMID- 28449872
TI  - Harnessing macrophage plasticity for tissue regeneration.
AB  - Macrophages are versatile and plastic effector cells of the immune system, and
      contribute to diverse immune functions including pathogen or apoptotic cell
      removal, inflammatory activation and resolution, and tissue healing. Macrophages
      function as signaling regulators and amplifiers, and influencing their activity
      is a powerful approach for controlling inflammation or inducing a wound-healing
      response in regenerative medicine. This review discusses biomaterials-based
      approaches for altering macrophage activity, approaches for targeting drugs to
      macrophages, and approaches for delivering macrophages themselves as a
      therapeutic intervention.

PMID- 28449874
TI  - Selectivity differences of coordination compound stationary phases for
      polyaromatic hydrocarbons and polar analytes in gas and liquid phases.
AB  - A precursor solution to the metal-organic framework (MOF), Cd(1,4,7,10-tetrakis(4
      carboxybenzyl)-1,4,7,10-tetraazacyclododecane), was aged in a surface
      functionalised 250MUm-diameter capillary, to generate a film containing the
      constituents of the bulk phase crystalline material. EDX analysis revealed a
      higher ratio of ligand elements (C, N and O) to Cd in the capillary coated phase
      compared to that achieved from bulk synthesis in a vial. Separation performance
      of the coated capillary for gas chromatography (GC) was compared to the
      performance of the original MOF crystals packed in tips for liquid elution
      chromatography (LEC) towards the separation of polycyclic aromatic hydrocarbons
      (PAHs) and small probe analytes with different properties. This study showed that
      different retention mechanisms were observed for the same set of analytes in gas
      and liquid phases. Independently of the trend of vapour pressure difference, the
      GC result showed less specific size selective retention, but with stronger
      retention towards larger PAHs. A linear solvation energy relationship correlation
      further revealed enhanced retention contributions (positive stationary phase
      descriptor values) by cavity formation/dispersion interactions and H-bonding with
      acid functionality of the probe analytes in both GC and LEC (though stronger in
      LEC), whilst H-bonding with basic functional groups slightly increased retention
      in GC; retention was strengthened by dipole-dipole/dipole-induced dipole
      interactions only in LEC.

PMID- 28449875
TI  - Development and validation of a quantitative confirmatory method for 30 beta
      lactam antibiotics in bovine muscle using liquid chromatography coupled to tandem
      mass spectrometry.
AB  - A method was developed for the confirmatory and quantitative analysis of 30 beta
      lactam antibiotic residues in bovine muscle. The method includes 12 penicillins
      (amoxicillin, ampicillin, cloxacillin, dicloxacillin, mecillinam, methicillin,
      nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, ticarcillin), 12
      cephalosporins (cefacetrile, cefadroxil, cephalexin, cefalonium, cefazolin,
      cefoperazone, cefotaxime, cefquinome, cefuroxime, desacetyl cephapirin,
      desfuroylceftiofur cysteine disulfide, desfuroylceftiofur dimer), five
      carbapenems (biapenem, doripenem, ertapenem, imipenem, meropenem) and faropenem.
      Samples were extracted using a simple solvent extraction with acetonitrile:water
      (80:20, v/v) and C18 dispersive solid-phase extraction (d-SPE) clean-up, followed
      by ultra-high performance liquid chromatography coupled to tandem mass
      spectrometry (UHPLC-MS/MS) detection. Chromatography was performed on a reversed
      phase CSH C18 column, using a binary gradient separation comprising of 0.01%
      formic acid and 0.2mM ammonium acetate in water (mobile phase A) and 0.01% formic
      acid in acetonitrile (mobile phase B). The mass spectrometer was operated in the
      positive electrospray ionisation mode (ESI(+)). Validation was performed
      following the 2002/657/EC guidelines. Trueness ranged between 69% and 143% and
      precision ranged between 2.0% and 29.9% under within-laboratory reproducibility
      conditions. The developed method uses minimal sample preparation and 30 test
      samples can be analysed by a single analyst in a single day. To the best of our
      knowledge, this is the first method for carbapenems in foodstuff that does not
      require derivatisation.

PMID- 28449876
TI  - Comprehensive two-dimensional gas chromatography in combination with pixel-based
      analysis for fouling tendency prediction.
AB  - Fouling tendencies of a series of gas condensates were evaluated using
      comprehensive two-dimensional gas chromatography with flame ionization detection
      and sulfur chemiluminescence detection. A pixel-based approach was applied in
      order to identify parts of the chromatograms which were associated with the
      reactor coil fouling. Particular emphasis is given in this work to evaluate
      several feature selection methodologies along with various data preprocessing
      procedures. It was found that both aspects were crucial for studying the fouling
      tendencies and, as part of the subsequent partial least squares model
      development, predominantly the feature selection. Based on the flame ionization
      detector chromatograms and using the RReliefF algorithm for feature selection, a
      partial least squares regression model with one latent variable resulted in a
      root mean square error of the cross-validation of 0.65gdeposit/6h (17%). Based on
      the sulfur chemiluminescence detector chromatograms, the F-statistics feature
      selection generated a slightly better partial least squares regression model
      compared to using RReliefF, thus generating a model using one latent variable
      with a root mean square error of the cross-validation of 0.81gdeposit/6h (21%).
      Heavy aromatic compounds and heavy sulfur containing compounds were negatively
      associated with the fouling rate. Both were crucial in developing a partial least
      squares model with good prediction power, however, worked independently as
      predictors.

PMID- 28449873
TI  - Progress in tumor-associated macrophage (TAM)-targeted therapeutics.
AB  - As an essential innate immune population for maintaining body homeostasis and
      warding off foreign pathogens, macrophages display high plasticity and perform
      diverse supportive functions specialized to different tissue compartments.
      Consequently, aberrance in macrophage functions contributes substantially to
      progression of several diseases including cancer, fibrosis, and diabetes. In the
      context of cancer, tumor-associated macrophages (TAMs) in tumor microenvironment
      (TME) typically promote cancer cell proliferation, immunosuppression, and
      angiogenesis in support of tumor growth and metastasis. Oftentimes, the abundance
      of TAMs in tumor is correlated with poor disease prognosis. Hence, significant
      attention has been drawn towards development of cancer immunotherapies targeting
      these TAMs; either depleting them from tumor, blocking their pro-tumoral
      functions, or restoring their immunostimulatory/tumoricidal properties. This
      review aims to introduce readers to various aspects in development and evaluation
      of TAM-targeted therapeutics in pre-clinical and clinical stages.

PMID- 28449877
TI  - Two stage algorithm vs commonly used approaches for the suspect screening of
      complex environmental samples analyzed via liquid chromatography high resolution
      time of flight mass spectroscopy: A test study.
AB  - LC-HR-QTOF-MS recently has become a commonly used approach for the analysis of
      complex samples. However, identification of small organic molecules in complex
      samples with the highest level of confidence is a challenging task. Here we
      report on the implementation of a two stage algorithm for LC-HR-QTOF-MS datasets.
      We compared the performances of the two stage algorithm, implemented via
      NIVA_MZ_AnalyzerTM, with two commonly used approaches (i.e. feature detection and
      XIC peak picking, implemented via UNIFI by Waters and TASQ by Bruker,
      respectively) for the suspect analysis of four influent wastewater samples. We
      first evaluated the cross platform compatibility of LC-HR-QTOF-MS datasets
      generated via instruments from two different manufacturers (i.e. Waters and
      Bruker). Our data showed that with an appropriate spectral weighting function the
      spectra recorded by the two tested instruments are comparable for our analytes.
      As a consequence, we were able to perform full spectral comparison between the
      data generated via the two studied instruments. Four extracts of wastewater
      influent were analyzed for 89 analytes, thus 356 detection cases. The analytes
      were divided into 158 detection cases of artificial suspect analytes (i.e.
      verified by target analysis) and 198 true suspects. The two stage algorithm
      resulted in a zero rate of false positive detection, based on the artificial
      suspect analytes while producing a rate of false negative detection of 0.12. For
      the conventional approaches, the rates of false positive detection varied between
      0.06 for UNIFI and 0.15 for TASQ. The rates of false negative detection for these
      methods ranged between 0.07 for TASQ and 0.09 for UNIFI. The effect of background
      signal complexity on the two stage algorithm was evaluated through the generation
      of a synthetic signal. We further discuss the boundaries of applicability of the
      two stage algorithm. The importance of background knowledge and experience in
      evaluating the reliability of results during the suspect screening was evaluated.

PMID- 28449878
TI  - Silica aerogel coated on metallic wire by phase separation of polystyrene for in
      tube solid phase microextraction.
AB  - In this research, an attempt was made toward synthesizing a sol-gel-based silica
      aerogel and its subsequent coating on a copper wire by phase separation of
      polystyrene. Adaption of this new approach enabled us to coat the metallic wire
      with powder materials. The use of this method for coating, led to the formation
      of a porous and thick structure of silica aerogel. The coated wire was placed in
      a needle and used as the sorbent for in-tube solid phase microextraction of
      chlorobenzenes (CBs). The superhydrophobicity of sorbent on extraction efficiency
      was investigated by using different ratios of
      tetraethylorthosilicate/methyltrimethoxysilane. The surface coated with the
      prepared silica aerogel by the phase separation of polystyrene showed high
      contact angle, approving the desired superhydrophobic properties. Effects of
      major parameters influencing the extraction efficiency including the extraction
      temperature, extraction time, ionic strength, desorption time were investigated
      and optimized. The limits of detection and quantification of the method under the
      optimized condition were 0.1-1.2 and 0.4-4.1ngL-1, respectively. The relative
      standard deviations (RSD%) at a concentration level of 10ngL-1 were between 4 and
      10% (n=3). The calibration curves of CBs showed linearity from 1 to100ngL-1.
      Eventually, the method was successfully applied to the extraction of model
      compounds from real water samples and relative recoveries varied from 88 to 115%.

PMID- 28449879
TI  - Separation of small interfering RNA stereoisomers using reversed-phase ion
      pairing chromatography.
AB  - Small interfering RNA (siRNA) therapeutics have received significant interest in
      recent years owing to their ability to elicit sequence-specific gene knockdown
      and subsequent suppression of protein expression. Chemical modifications can
      improve the hydrolytic stability and susceptibility of siRNAs to enzymatic
      degradation. One commonly used modification to improve hydrolytic stability, the
      replacement of the native phosphodiester linkage with a phosphorothioate moiety,
      introduces an additional phosphorous stereocenter into the molecule, resulting in
      the formation of diastereomers. The chromatographic separation of stereoisomeric
      siRNAs containing such phosphothioates is a challenging problem, especially when
      multiple phosphothioates are present within a modified siRNA duplex giving rise
      to multiple stereoisomers. In this study, we report an investigation into the use
      of an ion-pairing reversed phase UHPLC (or IP-RP UHPLC) method for the baseline
      separation of closely related diastereomers of an Apo-B gene targeting siRNA
      duplex under denaturing conditions. The related siRNA species consist of two
      diastereomers from the sense strand and the two pairs of diastereomers from the
      antisense strand. Key chromatographic parameters critical to stereoisomer
      separation are highlighted, including the structure of the ion-pairing agent,
      chemical composition of the stationary phase, and organic modifier. The method
      was applied to the separation of an siRNA stressed with iodine and demonstrated
      satisfactory selectivity for the parent siRNA and the desulfurization product.

PMID- 28449880
TI  - Benign focal amyotrophy.
AB  - Within lower motor neuron diseases, benign focal amyotrophy is a rare syndrome
      characterized by insidious neurogenic asymmetric atrophy restricted to upper or
      lower limbs with a good prognosis over time. Described under several terms, the
      nosology is probably heterogeneous. In juvenile distal upper-limbs forms,
      specific MRI signs with in particular a compression of the spinal cord by forward
      displacement of dura, lead to evoke a mechanical process. In other forms,
      occurring later in the life, affecting proximal part of upper limbs or lower
      limbs, the physiopathology is still unknown and a focal spinal muscular atrophy
      is suspected. In this review, we will discuss the clinical, electrophysiological
      and radiological features of each presentation.

PMID- 28449881
TI  - Genetics of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease characterized
      by upper and lower motor neuron damage in the bulbar and spinal territories.
      Although the pathophysiology of ALS is still unknown, the involvement of genetic
      factors is no longer a subject of debate. Familial ALS (fALS) accounts for 10-20%
      of cases. Since the identification of the SOD1 gene, more than 20 genes have been
      described, of which four can explain >50% of familial cases. This review is an
      update focused on major aspects of the field of ALS genetics concerning both
      causative and susceptibility factors.

PMID- 28449882
TI  - ALS and frontotemporal dementia belong to a common disease spectrum.
AB  - ALS is now understood to be a complex multisystem neurodegenerative disease
      because areas other than the motor cortices of the brain undergo degeneration.
      Frontotemporal dementia (FTD) may be associated with motor neuron disease, and
      the transactive response DNA-binding protein 43 (TDP-43) is a major pathological
      substrate underlying both diseases. The recent discovery of a gene that can cause
      both FTD, ALS and FTD-ALS, C9ORF72, has modified the way for considering these
      two pathologies. These findings would allow the development of potential
      biomarkers and therapeutic targets for these devastating diseases. This review
      summarizes the key points leading up to our current understanding of the genetic,
      clinical and neuropathological overlap between FTD and ALS.

PMID- 28449883
TI  - Hereditary spastic paraplegia: More than an upper motor neuron disease.
AB  - Hereditary spastic paraplegias (HSPs) are a group of rare inherited neurological
      diseases characterized by extreme heterogeneity in both their clinical
      manifestations and genetic backgrounds. Based on symptoms, HSPs can be divided
      into pure forms, presenting with pyramidal signs leading to lower-limb
      spasticity, and complex forms, when additional neurological or extraneurological
      symptoms are detected. The clinical diversity of HSPs partially reflects their
      underlying genetic backgrounds. To date, 76 loci and 58 corresponding genes
      [spastic paraplegia genes (SPGs)] have been linked to HSPs. The genetic diagnosis
      is further complicated by the fact that causative mutations of HSP can be
      inherited through all possible modes of transmission (autosomal-dominant and 
      recessive, X-linked, maternal), with some genes showing multiple inheritance
      patterns. The pathogenic mutations of SPGs primarily lead to progressive
      degeneration of the upper motor neurons (UMNs) comprising corticospinal tracts.
      However, it is possible to observe lower-limb muscle atrophy and fasciculations
      on clinical examination that are clear signs of lower motor neuron (LMN)
      involvement. The purpose of this review is to classify HSPs based on their degree
      of motor neuron involvement, distinguishing forms in which only UMNs are affected
      from those involving both UMN and LMN degeneration, and to describe their
      differential diagnosis from diseases such as amyotrophic lateral sclerosis.

PMID- 28449884
TI  - A rapidly changing global medicines environment: How adaptable are funding
      decision-making systems?
AB  - BACKGROUND: With the launch of very highly priced therapies and sudden price
      increases of generics, pressures on health systems have drastically increased.
      OBJECTIVES: We aimed to elicit opinions of key decision makers responsible for
      national assessment and funding decisions on their experiences to adapt to these
      new realities. METHODS/SETTING: Through interviews with decision makers of
      pharmaceutical assessment and/or funding agencies, we describe the challenges
      systems are currently facing, systems' responses and systems' characteristics
      facilitating or hindering responses to changes and overarching topics for the
      future. RESULTS: Among the most common challenges are increased funding
      pressures, increased uncertainty and lack of transparency in decision-making.
      Systems' responses include utilization management, changing of assessment
      processes, stakeholder engagement and a focus on outcomes and on coordinated
      negotiations. Integrated delivery systems, fixed health care budgets and
      geographic and historical characteristics facilitate or sometimes hinder
      responses to change. Future policy emphasis lays on expanding data structures,
      managing the exit of drugs funded early, and implementing processes for
      communications with patients and the public. CONCLUSIONS: Going forward emphasis
      has to be given to structured communications with all stakeholders with a
      specific emphasis on the broader public and patients about financial limits and
      priority setting in health care.

PMID- 28449885
TI  - Informal and formal care: Substitutes or complements in care for people with
      dementia? Empirical evidence for 8 European countries.
AB  - BACKGROUND: In order to contain public health care spending, European countries
      attempt to promote informal caregiving. However, such a cost reducing strategy
      will only be successful if informal caregiving is a substitute for formal health
      care services. We therefore analyze the effect of informal caregiving for people
      with dementia on the use of several formal health care services. STUDY DESIGN:
      The empirical analysis is based on primary data generated by the EU-project
      'RightTimePlaceCare' which is conducted in 8 European countries. 1223 people with
      dementia receiving informal care at home were included in the study. METHODS:
      Using a regression framework we analyze the relationship between informal care
      and three different formal health care services: the receipt of professional home
      care, the number of nurse visits and the number of outpatient visits. RESULTS:
      The relationship between formal and informal care depends on the specific type of
      formal care analyzed. For example, a higher amount of informal caregiving goes
      along with a lower demand for home care services and nurse visits but a higher
      number of outpatient visits. CONCLUSION: Increased informal caregiving
      effectively reduces public health care spending by reducing the amount of formal
      home care services. However, these effects differ between countries.

PMID- 28449886
TI  - A novel postal-based approach to diagnosing obstructive sleep apnoea in a high
      risk population.
AB  - OBJECTIVE: More than 50% of patients with diabetic macular oedema (DMO) have
      obstructive sleep apnoea (OSA), but the majority remain undiagnosed. We used a
      four-channel device (ApneaLink [AL], ResMed, UK) to establish a remote postal
      based diagnostic service for patients with DMO. Here we describe our experience.
      METHODS: Patients with DMO were invited to participate. Interested patients
      returned a free-post reply slip to the study team, who posted an AL with
      pictorial and written instructions to them. Following a single night study, the
      AL was returned by a freepost service. RESULTS: Responses from 733 patients
      meeting the inclusion criteria were received, comprising 469 males and 264
      females, mean age 64 years (standard deviation 10.4 years). ALs were issued to
      718 patients, of whom 606 completed a diagnostic study. A total of 71 patients
      (12%) required a repeat study due to inadequacy of the first attempt. Completed
      sleep studies showed that 75% of respondents had sleep disordered breathing: 4%
      ODI 0-4/h, 24%; 5-9/h, 19%; 10-19/h, 23%; >=20/h, 34%; and AHI 0-4/h, 25%; 5
      14/h, 38%; 15-29/h, 20%; >=30/h, 17%. Among 1592 postal events through the
      national post service, 20 ALs were lost. CONCLUSIONS: We have demonstrated that a
      remote postal-based diagnostic service for populations with a high risk of OSA
      can be successfully performed. This novel approach, which avoids clinic
      attendance, may be useful in clinical practice.

PMID- 28449887
TI  - Sleep deficiency on school days in Icelandic youth, as assessed by wrist
      accelerometry.
AB  - AIMS: The purpose of this study was to objectively measure, with wrist-worn
      actigraphy, free-living sleeping patterns in Icelandic adolescents, and to
      compare sleep duration, sleep quality and clock times between school days (SchD)
      and non-school days (NSchD) and the association between sleep and body mass index
      (BMI). METHODS: A cross-sectional study on 15.9-year-old (+/-0.3) adolescents
      from six schools in Reykjavik, Iceland, took place in the spring of 2015. Free
      living sleep was measured on 301 subjects (122 boys and 179 girls) over seven
      days using wrist-worn actigraphy accelerometers. Total rest time (TRT), total
      sleep time (TST), sleep quality markers, and clock times for sleep were
      quantified and compared between SchD and NSchD and between the sexes, using
      paired and group t-tests as appropriate. Linear regression was used to assess the
      association between sleep parameters and BMI. RESULTS: On SchD, TST was 6.2 +/-
      0.7 h, with sleep efficiency (SLE) of 87.9 +/- 4.4% for the group. On NSchD, TST
      increased to 7.3 +/- 1.1 h (p < 0.001), although SLE decreased to 87.4 +/- 4.7%
      (p < 0.05). On SchD and NSchD, 67% and 93% had bed times after midnight,
      respectively, and on SchD 10.7% met sleep recommendations (8 h/night). There was
      no association between BMI and average sleep parameters. CONCLUSION: The majority
      of Icelandic adolescents did not get the recommended number of hours of sleep,
      especially on SchD. While TST increased on NSchD, many participants still did not
      achieve the recommendations. These findings provide information on the sleep
      patterns of adolescents and may serve as reference for development of policies
      and interventions to promote better sleep practices.

PMID- 28449888
TI  - Increasing presurgery sleep reduces postsurgery pain and analgesic use following
      joint replacement: a feasibility study.
AB  - STUDY OBJECTIVES: To determine whether presurgery sleep extension in short
      sleeping volunteers scheduled for total knee/hip replacement surgery would reduce
      postsurgery pain and analgesic use. METHODS: Eighteen short sleepers, defined by
      sleep times below the national mean (ie, <=7 h) nightly, were randomized to one
      week of a 2-h nightly extension of their time in bed (EXT) or maintenance of
      their habitual time in bed (HAB) prior to knee or hip replacement surgery.
      Compliance was monitored by wrist actigraphy. Outcomes were the postsurgery daily
      dose of opiates (converted to morphine milligram equivalents) and the daily pain
      ratings (acquired 3-4 times across the day) on a 0-10 rating scale (0 = no pain
      to 10 = worst pain experienced) over the three to four day inpatient recovery.
      RESULTS: On a diary before the presurgery time in bed (TIB) manipulation, there
      were no significant differences in reported nightly sleep times between those
      randomized to the EXT group [6.0 (+/-0.78) h] and the HAB group [6.5 (+/-0.50)
      h]. During the one-week presurgery TIB manipulation, three participants failed to
      extend their TIB. Among those extending TIB (n = 7), compared to the HAB group,
      the EXT group spent significantly more nightly TIB (8.0 vs. 6.9 h, p < 0.05),
      which resulted in 1 h of more sleep (6.8 vs. 5.8 h, p < 0.04). On the three- to
      four-day postsurgery inpatient recovery, the EXT group reported significantly
      less average daily pain (4.4 vs. 5.6, p < 0.04) and less daily morphine milligram
      equivalent intake (20.3 vs. 38.6 mg, p < 0.02) than those by the HAB group.
      CONCLUSIONS: In this feasibility study, we found that a presurgery extended TIB
      and associated increase in sleep time in short-sleeping patients scheduled for
      undergoing joint replacement results in reduced postsurgery pain ratings and
      opiate use.

PMID- 28449889
TI  - Treating sleep apnea in Parkinson's disease with C-PAP: feasibility concerns and
      effects on cognition and alertness.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in Parkinson
      disease (PD) and is known to contribute to cognitive impairment and daytime
      sleepiness. We investigated feasibility of continuous positive airway pressure
      treatment (CPAP) and its effects on subjective daytime sleepiness and cognitive
      profile in PD plus OSA subjects in a longitudinal three months follow up study.
      METHODS: Seventy (age 71.7 +/- 7.6, disease duration 9.9 +/- 12.3, UPDRS-III 33.7
      +/- 12.5, MMSE 25.3 +/- 3.6; years of education 7.7 +/- 3.2) out of 228
      consecutive PD patients undergoing in-lab video-polysomnography were found to
      have obstructive sleep apnea. Thirty-six subjects accepted to titrate therapeutic
      CPAP. Video-polysomnography, neuropsychological battery evaluating different
      cognitive domains and subjective scales for daytime sleepiness were scheduled at
      baseline and after three months. All the patients were given educational
      informations relative to diagnosis of OSA and benefits of OSA treatment, and an
      individualized training with CPAP. RESULTS: Twenty-seven (75%) subjects dropped
      out of the study due to CPAP intolerance. No demographic or disease-related
      variables (in particular, severity of OSA), could be found between subjects who
      completed the study versus those who dropped out. Nine subjects completed the
      three-month follow up, and there were no significant changes in subjective
      sleepiness, neuropsychological scores and sleep structure (except for reduction
      in apnea/hypopnea index and a trend toward increase in stage N3 sleep).
      CONCLUSION: Our data show that feasibility of CPAP treatment can be significantly
      threatened by overall attrition rates. Further studies should consider well
      structured adherence promoting interventions. The actual role of OSA as a
      determinant of the profile of subjective daytime sleepiness and cognition in PD,
      and the effects of CPAP in PD need to be further studied.

PMID- 28449890
TI  - Age- and gender-specific associations of napping duration with type 2 diabetes
      mellitus in a Chinese rural population: the RuralDiab study.
AB  - BACKGROUND: The consistency and strength of the relationship between napping
      duration and type 2 diabetes mellitus (T2DM) remained uncertain, especially in
      the rural population. The purpose of this study was to explore the relationship
      between napping duration and T2DM in a Chinese rural population. METHODS: A total
      of 12663 participants (4365 males and 8298 females) were derived from the
      RuralDiab study in China. Napping duration was obtained through a standardized
      questionnaire, and was divided into five categories: no napping (reference), 1~,
      31~, 61~, and >=91 min. Fasting blood glucose was measured. Logistic regression
      was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A meta
      analysis including seven studies was conducted to validate the result of the
      RuralDiab study. RESULTS: The crude and age-standardized prevalence of T2DM were
      10.31% and 8.14%, respectively. Compared with no napping, the adjusted OR (95%CI)
      for napping duration >=91 min was 1.23 (1.05-1.45). A similar relationship was
      found only in females aged 45-54 years, but not in males and other age group
      females. In addition, napping duration was associated with T2DM in a positive
      dose-dependent manner among females aged 45-54 years (P for trend <0.05). The
      meta-analysis demonstrated this association, and the pooled OR (95%CI) for the
      longest napping duration compared with no napping was 1.28 (1.22-1.35).
      CONCLUSION: Longer napping duration is associated with higher risk of T2DM in the
      Chinese rural population, and this association varies across gender and age.
      Further multi-center prospective researches are needed to confirm the
      relationship and reveal underlying mechanisms.

PMID- 28449891
TI  - The European Medicines Agency review of pitolisant for treatment of narcolepsy:
      summary of the scientific assessment by the Committee for Medicinal Products for
      Human Use.
AB  - On 31 March 2016, the European Commission issued a decision for a marketing
      authorisation valid throughout the European Union (EU) for pitolisant (Wakix) for
      the treatment of narcolepsy with or without cataplexy in adults. Pitolisant is an
      antagonist/inverse agonist of the human histamine H3 receptor. The dose should be
      selected using an up-titration scheme depending on individual patient response
      and tolerance and should not exceed 36 mg/day. The main evidence of efficacy of
      pitolisant was based on two Phase III clinical trials. The improvement on
      excessive daytime sleepiness was shown against placebo in the Harmony I study (
      3.33 points; 95% confidence interval (CI) [-5.83; -0.83]; p = 0.024) and in
      Harmony CTP (-3.41 points; 95% CI [-4.95; -1.87]; p < 0.0001). The daily
      cataplexy rate in Harmony I improved against placebo with a rate ratio (rR) of
      0.38 whilst in the Harmony CTP the ratio of improvement on weekly cataplexy rate
      against placebo was 0.512. The most commonly reported adverse reactions were
      headache, insomnia and nausea. This article summarizes the scientific review
      leading to approval of pitolisant in the EU. The assessment report and product
      information are available on the European Medicines Agency website
      (http://www.ema.europa.eu).

PMID- 28449892
TI  - Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease
      (BOND) study.
AB  - OBJECTIVE/BACKGROUND: The objective of this study was to evaluate medical
      comorbidity patterns in patients with a narcolepsy diagnosis in the United
      States. PATIENTS/METHODS: This was a retrospective medical claims data analysis.
      Truven Health Analytics MarketScan(r) Research Databases were accessed to
      identify individuals >=18 years of age with >=1 diagnosis code for narcolepsy
      (International Classification of Diseases (ICD)-9, 347.0, 347.00, 347.01, 347.1,
      347.10, or 347.11) continuously insured between 2006 and 2010, and controls
      without narcolepsy matched 5:1 on age, gender, region, and payer. Narcolepsy and
      control subjects were compared for frequency of comorbid conditions, identified
      by the appearance of >1 diagnosis code(s) mapped to a Clinical Classification
      System (CCS) level 1 category any time during the study period, and on specific
      subcategories, including recognized narcolepsy comorbidities of obstructive sleep
      apnea (OSA) and depression. RESULTS: The final study group included 9312 subjects
      with narcolepsy and 46,559 controls (each group: average age, 46.1 years; 59%
      female). As compared with controls, patients with narcolepsy showed a
      statistically significant excess prevalence in all the CCS multilevel categories,
      the only exceptions being conditions originating in the perinatal period and
      pregnancy/childbirth complications. The greatest excess prevalence in the
      narcolepsy cohort was seen for mental illness (31.1% excess prevalence; odds
      ratio (OR) 3.8, 95% confidence interval (CI) 3.6, 4.0), followed by diseases of
      the digestive system (21.4% excess prevalence; OR 2.7, 95% CI 2.5, 2.8) and
      nervous system/sense organs (excluding narcolepsy; 20.7% excess prevalence; OR
      3.7, 95% CI 3.4, 3.9). CONCLUSIONS: In this claims analysis, a narcolepsy
      diagnosis was associated with a wide range of comorbid medical illness claims, at
      significantly higher rates than matched controls.

PMID- 28449893
TI  - Higher sleep reactivity and insomnia mutually aggravate depressive symptoms: a
      cross-sectional epidemiological study in Japan.
AB  - OBJECTIVE: Sleep reactivity assessed using the Ford Insomnia Response to Stress
      Test (FIRST) is associated with depression. This study clarified stress
      reactivity and insomnia effects on depressive symptoms. METHODS: A cross
      sectional questionnaire survey was administered to 2645 participating government
      employees (35.4% female, mean age 42.8 years) during health checks conducted at
      Tottori prefecture, Japan, in June 2012. Questionnaire items included:
      demographic information; the FIRST; the Pittsburgh Sleep Quality Index (PSQI);
      and a 12-item version of the Center for Epidemiological Studies Depression scale
      (CES-D). The study defined CES-D scores of >=12 points as positive for
      depression, PSQI scores of >=5.5 points as positive for insomnia symptoms, and
      FIRST scores of >=19 points as indicating higher sleep reactivity. RESULTS:
      Multivariate logistic regression analysis revealed insomnia (adjusted OR = 3.40),
      higher sleep reactivity (adjusted OR = 1.78), presence of disease currently being
      treated (adjusted OR = 1.84), and being female (adjusted OR = 1.53) as
      independently associated with depression. Participants with insomnia and a high
      FIRST score showed higher CES-D scores than those with insomnia alone and those
      with high FIRST without insomnia (all p < 0.01). CONCLUSIONS: Sleep reactivity
      might be associated with depression, independent of insomnia. Elevated sleep
      reactivity and insomnia symptoms are thought to aggravate depressive symptoms.

PMID- 28449895
TI  - The effect of continuous positive airway pressure on post-traumatic stress
      disorder symptoms in veterans with post-traumatic stress disorder and obstructive
      sleep apnea: a prospective study.
AB  - OBJECTIVES: Previous retrospective studies have shown that continuous positive
      airway pressure (CPAP) exerts salutary effect on post-traumatic stress disorder
      (PTSD) symptoms and nightmare distress. The relative magnitude of therapeutic
      benefits from CPAP and the strength of associations between duration of CPAP use
      and PTSD symptomatology are unknown. METHODS: A prospective cohort design
      involving 47 combat veterans with PTSD and documented obstructive sleep apnea
      (OSA) by overnight polysomnography. Epworth Sleepiness Scale (ESS) score, PTSD
      checklist-Military (PCL-M), Nightmare Distress Questionnaire (NDQ), and Nightmare
      Frequency Questionnaire (NFQ) were administered at baseline and 3 months after
      CPAP therapy. Objective adherence was assessed at the 3-month follow-up. RESULTS:
      Twenty-two veterans with mild-to-moderate PTSD (PCL-M score 17-59) and 18 with
      severe-to-very-severe PTSD (PCL-M score 60-85) completed the study. There was a
      dose-dependent response of PCL-M to duration of CPAP usage (r = 0.45; p = 0.003).
      Veterans with severe-to-very-severe PTSD had a larger improvement in PTSD
      symptoms (d = 0.65; p = 0.004) compared with those with mild-to-moderate PTSD (d
      = 0.47; p = 0.04). CPAP usage was the only significant predictor of overall
      subjective improvement in PTSD symptoms (OR 10.5; p = 0.01). Significant changes
      in NDQ and NFQ scores following 3 months of treatment were observed in veterans
      adherent to CPAP, but the correlations with duration of CPAP use were not
      statistically significant (r = 0.24; p = 0.13 and r = 0.13; p = 0.4,
      respectively). CONCLUSIONS: Improvement of PTSD symptoms in veterans with OSA was
      more pronounced with prolonged use of CPAP. Adherence to treatment was linked to
      abatement in nightmare distress and frequency. Future investigation of multimodal
      treatment, including behavioral intervention combined with CPAP, is warranted.

PMID- 28449894
TI  - Young children with Down syndrome show normal development of circadian rhythms,
      but poor sleep efficiency: a cross-sectional study across the first 60 months of
      life.
AB  - OBJECTIVES: To evaluate sleep consolidation and circadian activity rhythms in
      infants and toddlers with Down syndrome (DS) under light and socially entrained
      conditions within a familiar setting. Given previous human and animal data
      suggesting intact circadian regulation of melatonin across the day and night, it
      was hypothesized that behavioral indices of circadian rhythmicity would likewise
      be intact in the sample with DS. METHODS: A cross-sectional study of 66 infants
      and young children with DS, aged 5-67 months, and 43 typically developing age
      matched controls. Sleep and measures of circadian robustness or timing were
      quantified using continuous in-home actigraphy recordings performed over seven
      days. Circadian robustness was quantified via time series analysis of rest
      activity patterns. Phase markers of circadian timing were calculated alongside
      these values. Sleep efficiency was also estimated based on the actigraphy
      recordings. RESULTS: This study provided further evidence that general sleep
      quality is poor in infants and toddlers with DS, a population that has sleep
      apnea prevalence as high as 50% during the preschool years. Despite poor sleep
      quality, circadian rhythm and phase were preserved in children with DS and
      displayed similar developmental trajectories in cross-sectional comparisons with
      a typically developing (TD) cohort. In line with past work, lower sleep
      efficiency scores were quantified in the group with DS relative to TD children.
      Infants born with DS exhibited the worst sleep fragmentation; however, in both
      groups, sleep efficiency and consolidation increased across age. Three circadian
      phase markers showed that 35% of the recruitment sample with DS was phase
      advanced to an earlier morning schedule, suggesting significant within-group
      variability in the timing of their daily activity rhythms. CONCLUSIONS: Circadian
      rhythms of wake and sleep are robust in children born with DS. The present
      results suggest that sleep fragmentation and any resultant cognitive deficits are
      likely not confounded by corresponding deficits in circadian rhythms.

PMID- 28449896
TI  - Relationship between sleep disturbances and multimorbidity among community
      dwelling men and women aged 65-93 years: results from the KORA Age Study.
AB  - BACKGROUND/OBJECTIVE: Although the association of disturbed sleep with specific
      chronic conditions is well known, the relationship between sleep disturbances and
      multiple diseases is less clear. Therefore, the objectives of this study were to
      examine the independent relationships of various sleep disturbances with 1)
      multimorbidity (>=2 chronic conditions) and 2) commonly co-occurring pairs of
      chronic conditions. METHODS: Analyses were based on data from 4127 individuals
      aged >=65 years participating in the population-based cross-sectional Cooperative
      Health Research in the Region of Augsburg (KORA) Age Study conducted from 2008 to
      2009 in Germany. Sex-specific odds ratios (OR) and 95% confidence intervals (CI)
      were calculated from sequential logistic regression models. RESULTS: Neither
      short nor long daily sleep duration was significantly associated with
      multimorbidity among men; a significant positive relationship was identified
      regarding short sleep duration among women (OR 2.16, 95% CI: 1.42-3.30). While
      insomnia and all unique symptoms of insomnia were connected to multimorbidity
      among women in the multivariable models, the relationship concerning trouble
      falling asleep no longer remained significant after adjustment for all
      covariables among men. Regarding commonly co-occurring pairs of conditions, the
      clearest associations were observed between insomnia and daytime tiredness with
      joint diseases/eye diseases in men and joint diseases/heart diseases in women.
      CONCLUSIONS: There seems to be sex-specific particularities in the relationship
      between sleep disturbances and sleep duration with multimorbidity and commonly co
      occurring pairs of chronic conditions in older adults from the general
      population.

PMID- 28449897
TI  - Severe sleep apnea resistant to all treatments.

PMID- 28449898
TI  - Fatal familial insomnia: a video-polysomnographic case report.

PMID- 28449899
TI  - Comorbidity of narcolepsy with cataplexy and transverse myelitis: a common
      autoimmune background? A case report.

PMID- 28449900
TI  - Insufficient sleep rather than the apnea-hypopnea index can be associated with
      sleepiness-related driving problems of Japanese obstructive sleep apnea syndrome
      patients residing in metropolitan areas.
AB  - OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) and insufficient sleep might
      increase the risk of drowsy driving and sleepiness-related vehicular accidents.
      This study retrospectively investigated the factors associated with these driving
      problems, particularly addressing OSAS severity and sleep amounts of affected
      drivers. METHODS: This study examined 161 patients (146 male and 15 female) with
      OSAS (apnea-hypopnea index [AHI] >= 5) who drove on a routine basis and who
      completed study questionnaires. To investigate factors associated with drowsy
      driving during the prior year and sleepiness-related vehicular accidents or near
      miss events during the prior five years, logistic regression analyses were
      performed with age, body mass index, monthly driving distance, habitual sleep
      duration on weekdays, the Japanese version of Epworth Sleepiness Scale score,
      AHI, and periodic limb movement index as independent variables. RESULTS: Of the
      patients, 68 (42.2%) reported drowsy driving experiences, and 86 (53.4%) reported
      sleepiness-related vehicular accidents or near-miss events. Analyses revealed the
      following: older age (46-65 years, >=66 years) was negatively associated with
      drowsy driving (p <0.05, p <0.05), and habitually shorter sleep duration on
      weekdays (<=6 hours) was positively associated with drowsy driving (p <0.01).
      Habitual sleep duration of <=6 hours (p <0.01) and Epworth Sleepiness Scale score
      of >=11 (p <0.01) were positively associated with sleepiness-related vehicular
      accidents and near-miss events. However, AHI was not associated with these
      driving problems. CONCLUSION: Insufficient sleep, rather than severity of OSAS,
      was associated with sleepiness-related driving problems in these Japanese OSAS
      patients.

PMID- 28449901
TI  - Diagnostic REM sleep muscle activity thresholds in patients with idiopathic REM
      sleep behavior disorder with and without obstructive sleep apnea.
AB  - OBJECTIVES: We aimed to determine whether visual and automated rapid eye movement
      (REM) sleep without atonia (RSWA) methods could accurately diagnose patients with
      idiopathic REM sleep behavior disorder (iRBD) and comorbid obstructive sleep
      apnea (OSA). METHODS: In iRBD patients (n = 15) and matched controls (n = 30)
      with and without OSA, we visually analyzed RSWA phasic burst durations, phasic,
      tonic, and "any" muscle activity by 3-s mini-epochs, phasic activity by 30-s
      (AASM rules) epochs, and automated REM atonia index (RAI). Group RSWA metrics
      were analyzed with regression models. Receiver operating characteristic (ROC)
      curves were used to determine the best diagnostic cutoff thresholds for REM sleep
      behavior disorder (RBD). Both split-night and full-night polysomnographic studies
      were analyzed. RESULTS: All mean RSWA phasic burst durations and muscle
      activities were higher in iRBD patients than in controls (p <0.01). Muscle
      activity (phasic, "any") cutoffs for 3-s mini-epoch scorings were as follows:
      submentalis (SM) (15.8%, 19.5%), anterior tibialis (AT) (29.7%, 29.7%), and
      combined SM/AT (39.5%, 39.5%). The tonic muscle activity cutoff was 0.70% and RAI
      (SM) cutoff 0.86. The phasic muscle burst duration cutoffs were 0.66 s for SM and
      0.71 s for AT. Combining phasic burst durations with RSWA muscle activity
      improved the sensitivity and specificity of iRBD diagnosis. CONCLUSIONS: This
      study provides evidence for quantitative RSWA diagnostic thresholds applicable in
      iRBD patients with OSA. Our findings in this study were very similar to those
      seen in patients with Parkinson's disease-REM sleep behavior disorder (PD-RBD),
      consistent with a common mechanism and presumed underlying etiology of
      synucleinopathy in both groups.

PMID- 28449902
TI  - Validation of the Epworth Sleepiness Scale for Children and Adolescents using
      Rasch analysis.
AB  - OBJECTIVE: A validated measure of daytime sleepiness for adolescents is needed to
      better explore emerging relationships between sleepiness and the mental and
      physical health of adolescents. The Epworth Sleepiness Scale (ESS) is a widely
      used scale for daytime sleepiness in adults but contains references to alcohol
      and driving. The Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD)
      has been proposed as the official modified version of the ESS for children and
      adolescents. This study describes the psychometric analysis of the ESS-CHAD as a
      measure of daytime sleepiness for adolescents. METHODS: The ESS-CHAD was
      completed by 297 adolescents, 12-18 years old, from two independent schools in
      Victoria, Australia. Exploratory factor analysis and Rasch analysis was conducted
      to determine the validity of the scale. RESULTS: Exploratory factor analysis and
      Rasch analysis indicated that ESS-CHAD has internal validity and a unidimensional
      structure with good model fit. Rasch analysis of four subgroups based on gender
      and year-level were consistent with the overall results. The results were
      consistent with published ESS results, which strongly indicates that the changes
      to the scale do not affect the scale's capacity to measure daytime sleepiness.
      CONCLUSIONS: It is concluded that the ESS-CHAD is a reliable and internally valid
      measure of daytime sleepiness in adolescents 12-18 years old. Further studies are
      needed to establish the internal validity of the ESS-CHAD for children under 12
      years, and to establish external validity and accurate cut-off points for
      children and adolescents.

PMID- 28449903
TI  - Individuals with pain need more sleep in the early stage of mild traumatic brain
      injury.
AB  - OBJECTIVE: Hypersomnia is frequently reported after mild traumatic brain injury
      (mTBI), but its cause(s) remain elusive. This study examined sleep/wake activity
      after mTBI and its association with pain, a comorbidity often associated with
      insomnia. METHODS: Actigraphy recording was performed for 7 +/- 2 consecutive
      days in 56 individuals at one month post-mTBI (64% male; 38 +/- 12 years), 24
      individuals at one year post-mTBI (58% male; 44 +/- 11years), and in 20 controls
      (50% male; 37 +/- 12 years). Pain intensity and its effect on quality of life was
      assessed with a visual analogue scale and the Short Form Health Survey (SF-36)
      bodily pain subscale. RESULTS: Overall, few differences in sleep/wake patterns
      were found between mTBI patients and controls. However, higher percentages of
      mTBI individuals with moderate-to-severe pain were found to require more than
      eight hours of sleep per day (37% vs11%; p = 0.04) and to be frequent nappers
      (defined as those who took three or more naps per week) (42% vs 22%; p = 0.04)
      compared to those with mild or no pain at one month postinjury. Correcting for
      age and depression, The SF-36 score was found to be a significant predictor of
      sleep duration exceeding eight hours per day at one month (odds ratio = 0.95; 95%
      confidence interval = 0.92-0.99; p = 0.01), but not at one year post-mTBI. Pain
      and increased sleep need (in terms of hours per day or napping frequency) were
      found to co-exist in as much as 29% of mTBI patients at one month postinjury.
      CONCLUSION: Pain could be associated with more pronounced sleep need in about one
      third of mTBI patients during early recovery. Unalleviated pain, found in more
      than 60% of mTBI patients, should therefore be looked for in all mTBI patients
      reporting new onset of sleep disorder, not only in those with insomnia.

PMID- 28449904
TI  - Video-polysomnographic aspects of painful legs and moving toes syndrome.

PMID- 28449905
TI  - Sleep-wake patterns, non-rapid eye movement, and rapid eye movement sleep cycles
      in teenage narcolepsy.
AB  - BACKGROUND: To further characterize sleep disorders associated with narcolepsy,
      we assessed the sleep-wake patterns, rapid eye movement (REM), and non-REM (NREM)
      sleep cycles in Chinese teenagers with narcolepsy. METHODS: A total of 14 Chinese
      type 1 narcoleptic patients (13.4 +/- 2.6 years of age) and 14 healthy age- and
      sex-matched control subjects (13.6 +/- 1.8 years of age) were recruited.
      Ambulatory 24-h polysomnography was recorded for two days, with test subjects
      adapting to the instruments on day one and the study data collection performed on
      day two. RESULTS: Compared with the controls, the narcoleptic patients showed a
      1.5-fold increase in total sleep time over 24 h, characterized by enhanced slow
      wave sleep and REM sleep. Frequent sleep-wake transitions were identified in
      nocturnal sleep with all sleep stages switching to wakefulness, with more
      awakenings and time spent in wakefulness after sleep onset. Despite eight cases
      of narcolepsy with sleep onset REM periods at night, the mean duration of NREM
      REM sleep cycle episode and the ratio of REM/NREM sleep between patients and
      controls were not significantly different. CONCLUSION: Our study identified
      hypersomnia in teenage narcolepsy despite excessive daytime sleepiness. Sleep
      fragmentation extended to all sleep stages, indicating impaired sleep-wake cycles
      and instability of sleep stages. The limited effects on NREM-REM sleep cycles
      suggest the relative conservation of ultradian regulation of sleep.

PMID- 28449906
TI  - Low cerebrospinal fluid hypocretin levels during sudden infant death syndrome
      (SIDS) risk period.
AB  - OBJECTIVES: The temporal association between sudden infant death syndrome (SIDS)
      and sleep suggests that the arousability from sleep provides a protective
      mechanism for survival. Recently, the hypocretin system, which promotes
      wakefulness, has been implicated in SIDS, since it has been reported that SIDS
      victims have fewer hypocretin neurons than infants who have died from other
      causes. To understand the role of hypocretin in SIDS, it is essential to better
      understand how this system matures. The present study compared cerebrospinal
      fluid (CSF) hypocretin in children aged 2-6 months, which is the age of peak
      incidence for SIDS, to both younger and older children. METHOD: Hypocretin levels
      were measured in CSF samples from 101 children who underwent a clinically
      relevant lumbar puncture. Children were separated into five age groups: 0-2
      months, 2-6 months, 1-5 years, 5-10 years, and 10-18 years. RESULTS: Hypocretin
      levels were not significantly different between 1-5 years, 5-10 years, and 10-18
      years. Therefore, these three groups were pooled into a single one (1-18 years)
      for further analysis. Between the 0-2 month, 2-6 month, and 1-18 year groups, a
      significant difference in CSF hypocretin levels existed (p = 0.001). Simple
      comparisons showed that CSF hypocretin levels in the 2-6 month age group were
      significantly lower than hypocretin levels in both the 0-2 month and 1-18 year
      group (p < 0.001 and p = 0.008, respectively), but not significantly between 0-2
      month and 1-18 year children. CONCLUSIONS: The CSF hypocretin levels were lower
      at the age of peak incidence for SIDS. This could underlie an increased
      vulnerability to SIDS at this specific age.

PMID- 28449907
TI  - Reciprocal dynamics between self-rated sleep and symptoms of depression and
      anxiety in young adult women: a 14-day diary study.
AB  - OBJECTIVES: The objective of this study was to characterize the day-to-day
      associations among sleep disturbance, depression, and anxiety in a sample of
      young adult women. METHODS: One hundred and seventy-one women (20.1 +/- 3.3
      years) completed in-laboratory baseline assessment followed by daily online
      surveys across a two-week period. Daily measures included the Mood and Anxiety
      Symptom Questionnaire-Short Form to assess shared and disorder-specific symptoms
      of depression and anxiety (general distress, anhedonic depression, and anxious
      arousal), as well as self-reported total sleep time (TST), sleep-onset latency
      (SOL), and sleep quality (SQ). RESULTS: Findings supported bidirectional day-to
      day relationships between sleep and affective symptoms. When women felt greater
      general distress (shared features of anxiety and depression), they experienced
      longer SOL and worse SQ at night. Specificity among depression, anxiety, and
      sleep disturbance was observed such that higher levels of depression-specific
      anhedonia presaged longer SOL, shorter TST, and poorer SQ. In the other
      direction, when women had poor-quality sleep, they later experienced greater
      anhedonic depression and anxious arousal. The influence of TST on anhedonia was
      complex such that a single night of short sleep led to less anhedonic depression
      the next day, whereas women who obtained shorter sleep across the two-week period
      reported greater anhedonia. CONCLUSIONS: Reciprocal dynamics between nightly
      sleep disturbance and daily experiences of depression and anxiety may serve as a
      process by which insomnia, depression, and anxiety develop into comorbid clinical
      states over time in women. The associations of anhedonic depression with nightly
      sleep disturbance and chronic short sleep were especially toxic, offering insight
      into daily mechanisms driving the most prevalent phenotype of comorbid insomnia.

PMID- 28449908
TI  - Association of sleep-disordered breathing and disturbed cardiac repolarization in
      patients with ST-segment elevation myocardial infarction.
AB  - OBJECTIVE: In patients with ST-segment elevation myocardial infarction (STEMI),
      disturbed cardiac repolarization before percutaneous coronary intervention (PCI)
      is a risk factor for malignant ventricular arrhythmia. We tested the hypothesis
      that sleep-disordered breathing (SDB) in patients with STEMI is associated with
      disturbed cardiac repolarization. METHODS: Thirty-three patients with STEMI who
      underwent PCI were prospectively enrolled. To assess cardiac repolarization, the
      heart-rate corrected interval from the peak of the T wave to the end of the T
      wave (TpTec) and QTc intervals were assessed with 12-lead electrocardiography
      before PCI, within 24 h after PCI, and 12 weeks after PCI. SDB defined as an
      apnea-hypopnea index (AHI) >=15 per hour was diagnosed by polysomnography.
      RESULTS: Before PCI, patients with SDB had a significantly prolonged TpTec
      interval compared to patients without SDB (133 vs 104 ms, p = 0.035). Within 24 h
      after PCI, the TpTec interval was 107 vs 92 ms (p = 0.178). QTc intervals showed
      a similar pattern (pre-PCI: 443 vs 423 ms, p = 0.199; post-PCI: 458 vs 432 ms, p
      = 0.115). In multiple linear regression analyses, AHI was significantly
      associated with prolonged TpTec intervals (pre-PCI: B-coefficient = 1.11, 95%
      confidence interval (CI) 0.48-1.74, p = 0.001; post-PCI: B = 0.97, 95% CI 0.29
      1.65, p = 0.007), prolonged QTc intervals (pre-PCI: B = 1.05, 95% CI 0.20-1.91, p
      = 0.018; post-PCI: B = 1.37, 95% CI 0.51-2.24, p = 0.003), and higher TpTe/QT
      ratios (pre-PCI: B = 0.16, 95% CI 0.05-0.27, p = 0.007; post-PCI: B = 0.13, 95%
      CI < 0.01-0.25, p = 0.036), independent of known risk factors for cardiac
      arrhythmia. CONCLUSION: In patients with STEMI, SDB was significantly associated
      with disturbed cardiac repolarization before and after PCI, independent of known
      risk factors. These findings suggest that SDB may contribute to the risk of
      developing malignant ventricular arrhythmia.

PMID- 28449909
TI  - Head drops: electromyography may give the way.

PMID- 28449910
TI  - Effect of Tai Ji Quan training on self-reported sleep quality in elderly Chinese
      women with knee osteoarthritis: a randomized controlled trail.
AB  - OBJECTIVE: The purpose of this study was to explore the effects of a 24-week Tai
      Ji Quan training program on sleep quality, quality of life, and physical
      performance among elderly Chinese women with knee osteoarthritis (OA). METHODS: A
      24-week randomized, controlled trial of 46 elderly women with knee OA.
      Participants were randomly assigned to either a Tai Ji Quan group (n = 23) or a
      control group (n = 23). Participants in the Tai Ji Quan group completed training
      sessions three times per week, while those in the control group had bi-weekly
      educational classes. The primary outcome was total score of the Pittsburgh Sleep
      Quality of Index (PSQI). Secondary outcomes were: seven subscales of the PSQI;
      sleep latency; total sleep time; sleep efficiency; physical component summary
      (PCS) and mental component summary (MCS) of the 36-item Short Form Health Survey
      (SF-36); Berg Balance Scale (BBS); and Timed Up and Go (TUG). RESULTS: Compared
      with the control group, participants in the Tai Ji Quan group had significantly
      improved primary outcome (global PSQI score, p = 0.006) and secondary outcomes,
      including three PSQI sub-scores (sleep latency, p = 0.031; sleep duration, p =
      0.043; daytime dysfunction, p = 0.007), total sleep time (p = 0.033), and SF-36
      PCS (p = 0.006). The Tai Ji Quan group also had significant improvements compared
      with baseline in three PSQI sub-scores (sleep latency, p = 0.031; habitual sleep
      efficiency, p = 0.049; sleep disturbance, p = 0.016), sleep latency (p = 0.003),
      BBS (p = 0.001), and TUG (p = 0.006). CONCLUSION: Tai Ji Quan training is an
      effective treatment approach to improve sleep quality and quality of life in
      elderly Chinese women with knee OA. TRIAL REGISTRATION: Chinese Clinical Trial
      Registry (June 16, 2013): ChiCTR-TRC-13003264.

PMID- 28449911
TI  - Psychometric properties of the Sleep Condition Indicator and Insomnia Severity
      Index in the evaluation of insomnia disorder.
AB  - OBJECTIVE: The Sleep Condition Indicator (SCI) and Insomnia Severity Index (ISI)
      are commonly used instruments to assess insomnia. We evaluated their psychometric
      properties, particularly their discriminant validity against structured clinical
      interview (according to DSM-5 and ICSD-3), and their concurrent validity with
      measures of sleep and daytime functioning. METHODS: A total of 158 young adults,
      16% of whom were diagnosed with DSM-5 insomnia disorder and 13% with ICSD-3
      Chronic Insomnia by structured interview, completed the ISI and SCI twice in 7-14
      days, in addition to measures of sleep and daytime function. RESULTS: The Chinese
      version of the SCI was validated with good psychometric properties (ICC = 0.882).
      A cutoff of >=8 on the ISI, <=5 on the SCI short form, and <=21 on the SCI
      achieved high discriminant validity (AUC > 0.85) in identifying individuals with
      insomnia based on both DSM-5 and ICSD-3 criteria. The SCI and ISI had comparable
      associations with subjective (0.18 < r < 0.51) and actigraphic sleep (0.31 < r <
      0.43) and daytime functioning (0.34 < r < 0.53). CONCLUSION: The SCI, SCI short
      form, and ISI were found to correctly identify individuals with DSM-5- and ICSD-3
      defined insomnia disorder. Moreover, they showed good concordance with measures
      of daytime dysfunction, as well as subjective and objective sleep. The SCI and
      ISI are recommended for use in clinical and research settings.

PMID- 28449912
TI  - Infant night sleep trajectory from age 3-24 months: evidence from the Singapore
      GUSTO study.
AB  - OBJECTIVE: Longitudinal studies on night sleep trajectories throughout infancy
      are sparse. Moreover, most studies have examined samples in Caucasian
      individuals, although cultural differences in sleep habits have been described.
      To expand on the current literature, we aimed to determine night sleep
      trajectories in an Asian population from age 3-24 months. METHODS: Night sleep
      duration from a subset of 893 infants within the Growing Up in Singapore Towards
      healthy Outcomes (GUSTO) birth cohort study was determined using the caregiver
      reported Brief Infant Sleep Questionnaire. Latent growth curves were used to
      analyze sleep trajectories at 3, 6, 9, 12, 18, and 24 months. RESULTS: The
      overall trajectory was modeled with a piecewise model with two freely estimated
      curves. In the first phase (age 3-12 months), infants displayed an average
      curvilinear increase in night sleep trajectories of 0.12 h per month. In the
      second phase (age 12-24 months), infants continued to display a curvilinear
      increase, but at a slower average rate of 0.02 h per month. CONCLUSIONS: The
      sleep trajectory of Singaporean infants appeared similar to other predominantly
      Caucasian cohorts for 3-12 months but not for 12-24 months, in which infants from
      predominantly Caucasian cohorts mostly displayed a decreasing or a stable
      plateaued trajectory. This is in concordance with existing studies that suggest
      that the underlying influences of night sleep shift from predominantly biological
      influences to increasing environmental influences with age.

PMID- 28449914
TI  - Evaluation of sleep organization in patients with attention deficit hyperactivity
      disorder (ADHD) and ADHD as a comorbidity of epilepsy.
AB  - OBJECTIVE/BACKGROUND: Epilepsy or attention deficit hyperactivity disorder (ADHD)
      can influence sleep organization in different ways. The aim of this study was to
      evaluate sleep organization in children and adolescents with ADHD and epilepsy,
      and to analyze the influence of methylphenidate. METHODS: This was an
      observational, cross-sectional study of children and adolescents with epilepsy,
      who were seizure free for at least three months, and were also diagnosed with
      ADHD. They were selected from the epilepsy and child neurology outpatient clinic
      of a university hospital in Brazil. After sample size calculation, patients were
      consecutively included into four different groups, with 21 patients each:
      epilepsy + ADHD using methylphenidate, epilepsy + ADHD not using methylphenidate,
      only ADHD, and a healthy control group. All participants were evaluated with the
      Sleep Disturbance Scale for Children (SDSC) and monitored with actigraphy for
      five nights/days. RESULTS: Actigraphic analysis showed a higher number of night
      awakenings in the epilepsy + ADHD groups; they were most prominent in the group
      without methylphenidate (p = 0.001). Parental reports demonstrated a higher risk
      for sleep disturbances in the epilepsy + ADHD without methylphenidate and the
      ADHD groups (p < 0.001). CONCLUSION: Primary ADHD as a comorbidity of epilepsy
      impairs sleep organization in children, and the use of short-acting
      methylphenidate seems to improve it. Both objective (actigraphic) and subjective
      (SDSC) measures showed significant sleep alterations between primary ADHD and
      ADHD as a comorbidity of epilepsy; this was most prominent in the group without
      methylphenidate.

PMID- 28449913
TI  - Allostatic load in early pregnancy is associated with poor sleep quality.
AB  - BACKGROUND: Allostatic load (AL) measures the cumulative impact of chronic stress
      and is associated with adverse health outcomes. A novel scoring system has
      previously been developed for AL in early pregnancy that is associated with pre
      eclampsia. It was hypothesized that AL, as identified by the present model, is
      associated with psychosocial stressors and, specifically, poor sleep quality.
      METHODS: Women were selected from a low-risk, community-dwelling study population
      who enrolled at <15 weeks gestation. Nine physiologic components were divided
      among the domains of cardiovascular, metabolic, and inflammatory function.
      Spearman's rank correlations were used to examine the association of AL with age,
      income, the Revised Prenatal Distress Questionnaire (NuPDQ), Inventory of
      Depressive Symptoms (IDS), and Pittsburgh Sleep Quality Index (PSQI). The
      Wilcoxon rank-sum test was used to compare AL by race and educational attainment.
      RESULTS: A total of 103 women were identified, with: a mean age of 29.8 +/- 5.0
      years, 17.5% black, and mean gestational age 12.2 +/- 1.1 weeks. Allostatic load
      was positively correlated with the PSQI (rho = 0.23, p = 0.018). There were no
      associations with age, income, prenatal distress, race, or depression scores.
      College-educated women had lower AL compared with those with less education (0.57
      +/- 0.43 vs 0.81 +/- 0.55, p = 0.045). CONCLUSION: Higher AL, measured by the
      pregnancy-specific model, was associated with poorer sleep quality and lower
      educational attainment, both of which were considered to be chronic stressors.
      These relationships were consistent with previous findings in non-pregnant
      populations, and suggest that AL may be useful for capturing the physiologic
      impact of chronic stress in early pregnancy.

PMID- 28449915
TI  - High prevalence of poststroke sleep-disordered breathing in Mexican Americans.
AB  - OBJECTIVE: The purpose of this study is to compare sleep-disordered breathing
      (SDB) prevalence and severity after stroke between Mexican Americans (MAs) and
      non-Hispanic whites (NHWs). PATIENTS/METHODS: Ischemic stroke (IS) patients
      within ~30 days of onset were identified from the population-based BASIC Project
      (2010-2014) and offered screening with an overnight cardiopulmonary monitoring
      device, ApneaLink PlusTM. The number of apneas and hypopneas per hour, as
      reflected by the apnea/hypopnea index (AHI), was used to measure SDB severity;
      SDB was defined as AHI >=10. Ethnicity, demographics, and risk factors were
      collected from interviews and medical records. Log and negative-binomial
      regression models were used to determine prevalence ratios (PRs) and
      apnea/hypopnea event rate ratios (RRs) comparing MAs with NHWs after adjustment
      for demographics, risk factors, and stroke severity. RESULTS: A total of 549 IS
      cases had AHI data. The median age was 65 years (interquartile range (IQR): 57
      76), 55% were men, and 65% were MA. The MAs had a higher prevalence of SDB
      (68.5%) than NHWs (49.5%) in unadjusted (PR = 1.38; 95% confidence interval (CI):
      1.14-1.67) and adjusted analyses (PR = 1.21; 95% CI: 1.01-1.46). The median AHI
      was 16 (IQR: 7-31) in MAs and nine (IQR: 5-24) in NHWs. The severity of SDB (rate
      of apneas/hypopneas) was higher in MAs than NHWs in unadjusted (RR = 1.31; 95%
      CI: 1.09-1.58) but not adjusted analysis (RR = 1.14; 95% CI: 0.95-1.38). There
      was no ethnic difference in severity among subjects with SDB. CONCLUSION: More
      than two-thirds of MA stroke patients had SDB, which was almost 40% more common
      among MAs than NHWs. Physicians treating MA patients after stroke should have a
      high index of suspicion for SDB, a treatable condition that could otherwise have
      adverse impact.

PMID- 28449916
TI  - Psychosocial determinants of influenza vaccination intention: A cross-sectional
      study on inpatient nurses in Singapore.
AB  - Nurses have the closest interaction with inpatients and could transmit influenza
      to patients. From a self-administered questionnaire survey among inpatient nurses
      at a tertiary hospital, we observed that the strongest factors associated with
      intention for future vaccination were perceived benefits of and motivations for
      vaccination (adjusted odds ratio [aOR], 3.30; 95% confidence interval [CI], 2.55
      4.27), and perceived nonsusceptibility to influenza and preference for
      vaccination alternatives (aOR, 0.26; 95% CI, 0.20-0.34). These factors need to be
      addressed to increase vaccination uptake and prevent nosocomial transmission.

PMID- 28449917
TI  - Seroconversion rates among health care workers exposed to hepatitis C virus
      contaminated body fluids: The University of Pittsburgh 13-year experience.
AB  - BACKGROUND: Hepatitis C virus (HCV) transmission to health care personnel (HCP)
      after exposure to a HCV-positive source has been reported to occur at an average
      rate of 1.8% (range, 0%-10%). We aimed to determine the seroconversion rate after
      exposure to HCV-contaminated body fluid in a major U.S. academic medical center.
      METHODS: A longitudinal analysis of a prospectively maintained database of
      reported occupational injuries occurring between 2002 and 2015 at the University
      of Pittsburgh Medical Center was performed. Data collected include type of injury
      and fluid, injured body part, contamination of sharps, resident physicians'
      involvement, and patients' hepatitis B virus (HBV), HCV, and HIV status. RESULTS:
      A total of 1,361 cases were included in the study. Most exposures were caused by
      percutaneous injuries (65.0%), followed by mucocutaneous injuries (33.7%). Most
      (63.3%) were injuries to the hand, followed by the face and neck (27.6%). Blood
      exposure accounted for 72.7%, and blood-containing saliva accounted for 3.4%. A
      total of 6.9% and 3.7% of source patients were coinfected with HIV and HBV,
      respectively. The HCV seroconversion rate was 0.1% (n = 2) because of blood
      exposure secondary to percutaneous injuries. CONCLUSIONS: This study provides the
      largest and most recent cohort from a major U.S. academic medical center. The
      seroconversion rates among HCP exposed to HCV-contaminated body fluids was found
      to be lower than most of the data found in the literature.

PMID- 28449918
TI  - Better knowledge and regular vaccination practices correlate well with higher
      seasonal influenza vaccine uptake in people at risk: Promising survey results
      from a university outpatient clinic.
AB  - BACKGROUND: The knowledge, beliefs, opinions, and attitudes of patients and their
      relatives regarding seasonal influenza vaccination were evaluated. METHODS: This
      descriptive study was undertaken in the outpatient clinics of Baskent University
      Hospital. There were 566 responders who completed a self-administered
      questionnaire. RESULTS: The mean age of participants was 48.35 years, and 16.8%
      were >=65 years. Of the responders, 21.7% were vaccinated this year, whereas
      57.8% did not desire to get it. Vaccination rates were significantly higher among
      responders >=65 years of age (56.4%), those having at least 1 chronic illness
      (46.5%), and those who were vaccinated regularly every year (22.2%). Half of the
      responders did not know that the vaccine was reimbursed for people at risk. The
      most common reason for refusing the influenza vaccine was not getting the flu
      frequently (51.2%). Fear of side effects, concerns about vaccine's effectiveness,
      and belief that vaccine causes the flu were other common reasons for not being
      vaccinated. Of the responders, 77% believed that getting official information or
      a recommendation from a physician would influence their decision about seasonal
      influenza vaccination. CONCLUSIONS: People who are at risk or vaccinated
      regularly display a higher vaccine uptake and better knowledge of influenza and
      vaccination. The opinions and attitudes of this study population may assist in
      developing strategies for changing attitudes of the public toward influenza
      vaccination.

PMID- 28449919
TI  - Health care providers' perspectives for providing quality infection control
      measures at the neonatal intensive care unit, Cairo University Hospital.
AB  - BACKGROUND: Health care-associated infections are one of the major causes of
      morbidity and mortality in neonatal intensive care units (NICUs). This study
      identified health care providers' perspectives for providing quality infection
      control measures at a NICU. METHODS: A qualitative approach was adopted.
      Participants were selected via a purposive sampling technique. The study group
      was composed of 3 medical staff who held leadership positions and 10 nurses
      working in the NICU at Cairo University Hospital. Data were collected using semi
      structured interviews. RESULTS: Responses were analyzed using a thematic content
      analysis. The priorities identified by thematic analysis were suggestions and
      barriers for providing quality infection control measures, from the perspectives
      of health care providers. All interviewees cited shortage in staffing, especially
      nurses, lack of time to apply infection control standards, limited opportunities
      for infection control training, and work overload as the main barriers. All
      interviewees recommended on-going training and the introduction of audiovisual
      aids and case study approaches. CONCLUSIONS: Lack of time to apply infection
      control standards, limited opportunities for infection control training, and work
      overload are the most commonly perceived barriers. The current infection control
      system in the NICU is likely to remain ineffective unless these underlying
      barriers are adequately addressed.

PMID- 28449920
TI  - Validation of quality assurance criteria for rectal surveillance cultures.
AB  - We aimed to validate quality assurance (QA) criteria for rectal surveillance
      cultures (RSCs) for extended-spectrum beta-lactamase-producing
      Enterobacteriaceae. QA for RSCs were tested by observing the presence or absence
      of fecal soiling and by examining the growth of Enterobacteriaceae on MacConkey
      agar. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were detected
      in 136 out of 434 soiled swabs (31.3%) and in 61 out of 257 nonsoiled swabs
      (23.7%) (P = .036). Observation of fecal soiling on RSCs can serve as a simple QA
      criterion and prevent the reporting of false-negative results.

PMID- 28449921
TI  - Seroconversion rate among health care workers exposed to HIV-contaminated body
      fluids: The University of Pittsburgh 13-year experience.
AB  - BACKGROUND: The studies enumerating the risk of HIV transmission to health care
      workers (HCWs) as 0.3% after percutaneous exposure to HIV-positive blood, and
      0.09% after a mucous membrane exposure, are weakened by dated literature. Our
      study aims to demonstrate the seroconversion rate after exposure to HIV
      contaminated body fluids in a major academic center in the United States.
      METHODS: A prospectively maintained database of reported occupational injuries
      occurring between 2002 and 2015 at an academic medical center was analyzed. Data
      collected included the type of injury, injured body part, type of fluid,
      contamination of sharps, involvement of resident physicians, use of postexposure
      prophylaxis, and patients' HIV, hepatitis B virus, and hepatitis C virus status.
      RESULTS: A total of 266 cases were included in the study. Most exposures were
      caused by percutaneous injuries (52.6%), followed by 43.2% mucocutaneous
      injuries. Of the injuries, 52.6% were to the hand and 33.5% to the face and neck.
      Blood exposure accounted for 64.3% of all cases. Of the patients, 21.1% received
      postexposure prophylaxis. None of the HCWs exposed to HIV-contaminated body
      fluids seroconverted (seroconversion rate, 0%). CONCLUSIONS: HIV does not seem to
      be as easily transmitted by needlestick, laceration, or splash injuries as
      previously surmised. Further large-scale and multicenter studies are needed for a
      more accurate estimation of the risk of transmission of HIV in U.S. health care
      workers.

PMID- 28449922
TI  - Antimicrobial effect and physicochemical properties of an adhesive system
      containing nanocapsules.
AB  - OBJECTIVE: To incorporate indomethacin and triclosan-loaded nanocapsules into
      primer and adhesive, and evaluate its properties. METHODS: Indomethacin and
      triclosan were encapsulated by deposition of preformed polymer and subsequently
      characterized regarding morphology, particle size, drug content and cytotoxicity.
      Nanocapsules (NCs) were incorporated into primer at 2% and into adhesive at 1, 2,
      5, and 10% concentrations. Degree of conversion (DC) and softening in ethanol of
      the adhesive were evaluated. Drug release and drug diffusion through dentin was
      quantified by high performance liquid chromatography. Antimicrobial test was
      performed until 96h. RESULTS: Spherical and biocompatible NCs presented mean size
      of 159nm. Drugs content was 3mg indomethacin/g powder and 2mg triclosan/g powder.
      Incorporating NCs in adhesive showed no influence in DC (p=0.335). The addition
      of 2% of NCs showed no influence in softening in ethanol (p>0.05). After 120h,
      93% of indomethacin and 80% of triclosan were released from primer, 20% of
      indomethacin and 17% of triclosan were released from adhesive with 10% of NCs.
      Indomethacin showed diffusion through dentin. In 24h, adhesive containing 2 and
      5% of NCs using primer with NCs showed antimicrobial effect. In 96h, adhesives
      containing different concentration of NCs promoted antimicrobial effect.
      CONCLUSIONS: Indomethacin and triclosan-loaded nanocapsules were successfully
      incorporated into primer and adhesive, promoting controlled drugs release,
      indomethacin diffusion through dentin and antimicrobial effect without
      compromising its physicochemical properties. SIGNIFICANCE: Indomethacin and
      triclosan-loaded nanocapsules have potential to prevent recurrent caries and to
      be used in deep cavities controlling pulpar inflammatory process.

PMID- 28449924
TI  - Low-Volume vs High-Volume Centers and Management of Fournier's Gangrene in
      Washington State: In Reply to Yadav and colleagues.

PMID- 28449923
TI  - Semi-synthetic hydrogel composition and stiffness regulate neuronal
      morphogenesis.
AB  - This study describes the use of a set of protein-based biomaterials that allow us
      to explore the mechanism of cell-mediated 3-D invasion associated with peripheral
      nerve regeneration. Hydrogels made from poly(ethylene glycol) (PEG) conjugated
      extracellular matrix proteins, including fibrinogen, gelatin and albumin were
      compared in their ability to support the neurite extension and glial cell
      migration from dorsal root ganglion (DRG) as compared to PEG only hydrogel
      controls. The synthetic polymer in the system provides a cross-linked network
      with controlled mechanical properties and degradation, whereas the protein
      components provide the unique extracellular matrix (ECM) for controlling neuronal
      cell morphogenesis. A range of hydrogel compositions were found to support DRG
      cell outgrowth, based on the mechanical properties, density and proteolytic
      degradation of the matrix. The 3-D invasion and morphogenesis of newly grown
      neurites and glial cells in the different materials were characterized and
      correlated to the properties of the scaffolds. The DRG cell outgrowth was highly
      correlated with the density of different hydrogel compositions.

PMID- 28449925
TI  - Safety of Anesthetics in Children.

PMID- 28449926
TI  - On Foot Mat Use.

PMID- 28449927
TI  - May 2017 Featured Articles, Volume 224.

PMID- 28449928
TI  - Correction.

PMID- 28449929
TI  - Retraction notice.

PMID- 28449930
TI  - Invited Commentary: Some Considerations on Matching in Observational Studies.

PMID- 28449931
TI  - Invited Commentary: Education as a Pathway to Sustainable Improvement.

PMID- 28449932
TI  - Nonoperative Management of Appendicitis: The Need for Comparison with
      Laparoscopy, Plus Longer-Term Outcomes: In Reply to Talan and colleagues.

PMID- 28449934
TI  - Era of Individualization of the Surgical Treatment of Breast Cancer: Similar
      Problems Can Sometimes Be Treated Differently.

PMID- 28449933
TI  - Nonoperative Management of Appendicitis: Avoiding Hospitalization and Surgery.

PMID- 28449935
TI  - Should We Trust "Big Data" or "Meta-Data" to Guide Treatment for Patients with
      Resectable Esophageal Cancer?

PMID- 28449936
TI  - Interpreting the Evidence on Neoadjuvant Treatment of Esophageal Adenocarcinoma:
      In Reply to Yim and Colleagues.

PMID- 28449937
TI  - Statins and High-Risk Patients.

PMID- 28449938
TI  - Fournier's Gangrene.

PMID- 28449939
TI  - Subjective recollection independent from multifeatural context retrieval
      following damage to the posterior parietal cortex.
AB  - This study investigated whether damage to the posterior parietal cortex (PPC)
      impairs the capacity to retrieve multiple aspects of the encoding context in
      which items were studied, or whether it impairs the subjective awareness of
      recollection. Patients with lesions to the PPC (PPC patients) and healthy
      controls memorized words along with the position in which the words were
      presented on the screen and the ink color in which they were printed. We studied
      PPC patients' recognition and source memory performance, as well as subjective
      recollection as indexed by Remember/Know judgments. PPC patients had preserved
      recognition memory, and gave a similar number of R responses as did controls.
      Moreover, PPC patients' source memory performance, including memory for multiple
      contextual features, was similar to the controls'. However, whereas healthy
      controls were more likely to select R responses with correct multifeatural source
      judgments compared to K responses, PPC patients were not. These findings indicate
      that the PPC plays a role in the subjective experience and metamnemonic
      evaluation of memory contents.

PMID- 28449940
TI  - Antimicrobial activity of chemomechanical gingival retraction products.
AB  - BACKGROUND: Application of astringent hemostatic agents is the most widely used
      technique for gingival retraction, and a variety of products are offered
      commercially. However, these products may have additional unintended yet
      clinically beneficial properties. The authors assessed the antimicrobial
      activities of marketed retraction products against plaque-associated bacteria in
      both planktonic and biofilm assays, in vitro. METHODS: The authors assessed
      hemostatic solutions, gels, pellets, retraction cords, pastes, and their listed
      active agents against a collection of microorganisms by means of conventional
      agar diffusion and minimum bacteriostatic and bactericidal concentration
      determinations. The authors then tested the most active products against
      monospecies biofilms grown on hydroxyapatite disks. RESULTS: All of the tested
      retraction products exhibited some antimicrobial activity. The results of the
      most active products were comparable with those of a marketed mouthwash. The
      listed retraction-active agents displayed relatively little activity when tested
      in pure form. At 10% dilution, some products evidenced inhibitory activity
      against most tested bacteria within 3 minutes of exposure, whereas others
      displayed variable effects after 10 minutes. The most active agents reduced, but
      did not completely prevent, the metabolic activity of a monospecies biofilm.
      CONCLUSIONS: Commercial gingival retraction products exhibit antimicrobial
      effects to various degrees in vitro. Some products display rapid bactericidal
      activity. The antimicrobial activity is not owing to the retraction-active
      agents. Biofilm bacteria are less sensitive to the antimicrobial effects of the
      agents. PRACTICAL IMPLICATIONS: The rapidity of killing by some hemostatic agents
      suggests an antimicrobial effect that may be efficacious during clinical
      placement. The results of this in vitro study suggest that clinicians should be
      aware of the potential antimicrobial effects of some hemostatic agents, but more
      research is needed to confirm these observations in clinical use.

PMID- 28449941
TI  - Is C-reactive protein ready for prime time in the selection of antidepressant
      medications?

PMID- 28449942
TI  - Prevalence of honey bee (Apis mellifera) viruses in temperate and subtropical
      regions from Argentina.
AB  - In Argentina, bee virus studies are still incipient, and there are no studies
      regarding the climatic effect. The aim of this study was to assess and compare
      the presence of honeybee viruses in different climatic regions from Argentina. A
      total of 385 colonies distributed in five Argentinean eco-regions were examined
      to evaluate the percentage of infestation with Varroa destructor and the presence
      of seven virus species (Deformed wing virus, DWV; Acute bee paralysis virus,
      ABPV; Chronic bee paralysis virus, CBPV; Black queen cell virus, BQCV; Kashmer
      bee virus, KBV; Israeli acute bee paralysis virus, IAPV; and Sacbrood bee virus,
      SBV) after honey yield. Two viruses, KBV and IAPV, were not detected. The other
      five viruses were found in different prevalences: DWV (35%), ABPV (21.5%), BQCV
      (8.0%), CBPV (2.2%), and SBV (1.1%). We found double and triple viral
      associations in approximately 25% of the sampled colonies. The mean V. destructor
      infestation in the colonies prior to the acaricide treatment was 7.12%+/-8.7%.
      The knowledge of the prevalence of these viruses in the region and their relation
      with the mite and other possible influencing factors is important for preventing
      colony losses. Further studies are necessary to identify the risk factors
      associated with virus presence and its relationship with other pathogens such as
      V. destructor.

PMID- 28449943
TI  - Hearing loss education for older adults in primary care clinics: Benefits of a
      concise educational brochure.
AB  - Hearing loss, common in older adults, is associated with negative health outcomes
      but screening rates in primary care clinics are low and individuals screened or
      referred often do not follow-through. To address these problems, we worked with 2
      primary care clinics to design a simple screening and education protocol for
      integration into a standard office visit. To assess the effectiveness on the
      education brochure that was developed, we assessed its impact on individuals age
      60 or older who screened positive for possible hearing loss. Ninety-four of 125
      screened positive. Seventy-one agreed to participate and were given a brochure
      along with a brief review of the materials it contained. Of 67 completing follow
      up, 23 (34%) sought further testing and 47 (70%) had used the information to
      enhance communication. A simple educational brochure accompanied by a brief
      review of its contents may enhance effective use of hearing healthcare services.
      (147).

PMID- 28449944
TI  - Factors affecting nursing staff use of a communication tool to reduce potentially
      preventable acute care transfers in long-term care.
AB  - Although specialized communication tools can effectively reduce acute care
      transfers, few studies have assessed the factors that may influence the use of
      such tools by nursing staff at the individual level. We evaluated the
      associations between years of experience, tool-related training, nursing
      attitudes, and intensity of use of a communication tool developed to reduce
      transfers in a long-term care facility. We employed a mixed methods design using
      data from medical charts, electronic records, and semi-structured interviews.
      Experienced nurses used the tool significantly less than inexperienced nurses,
      and training had a significant positive impact on tool use. Nurses found the
      purpose of the tool to be confusing. No significant differences in attitude were
      observed based on years of experience or intensity of use. Project findings
      indicate that focused efforts to enrich training may increase intervention
      adherence. Experienced nurses in particular should be made aware of the benefits
      of utilizing communication tools.

PMID- 28449945
TI  - Blood Withdrawal from Intravenous Catheters by ED Nurses: Comparison of Two
      Practices.
AB  - CONTRIBUTION TO EMERGENCY NURSING PRACTICE: ABSTRACT PROBLEM: Laboratory tests
      are essential to diagnosis and treatment in the emergency department, but they
      can result in prolonged waiting times for patients, multiple needle pricks, and
      complaints about pain and discomfort. The goal of this project is to assess if a
      change in the blood collection process will lead to any improvement and benefit
      in care delivered with regard to time, patient comfort, and cost. METHODS: A
      feasibility study was conducted to evaluate the change in practice from cost,
      time, and applicability perspectives. Using an observational approach, data were
      collected about the management of a possible change in practice in the emergency
      department at American University of Beirut Medical Center. Trials of 2 proposed
      changes to practice were conducted and compared with the current practice. The
      nurses were trained in the proper use of blood withdrawal using a Vacutainer Luer
      adaptor. RESULTS: It was shown that intravenous line insertion and blood
      collection processes using the Vacutainer Luer adaptor were conducted in 46.2
      seconds, which is less time spent than the current process but requires a small
      investment. IMPLICATIONS FOR PRACTICE: Allowing registered nurses to withdraw
      blood with the start of a peripheral intravenous line will significantly reduce
      length of stay and costs and enhance patient experience in the emergency
      department at American University of Beirut Medical Center.

PMID- 28449946
TI  - Factors that influence the persistence and relapse of discriminated behavior
      chains.
AB  - Behavior chains are composed of sequences of behaviors that minimally include
      procurement and then consumption. This review surveys recent research from this
      laboratory that has examined the properties of discriminated heterogeneous
      behavior chains. In contrast to another review (Thrailkill and Bouton, 2016a), it
      discusses work examining what makes chained behavior persistent, and what makes
      it relapse. Results suggest that responses in a discriminated heterogeneous
      behavior chain may become associated, so that extinction of either one reduces
      the strength of the other. Evidence also suggests that the goal of the first
      (procurement) response may be the next (consumption) response (rather than the
      upcoming discriminative stimulus, a putative conditioned reinforcer, or the
      primary reinforcer at the end of the chain). Further studies suggest that methods
      that promote generalization across acquisition and extinction (partial
      reinforcement and delivery of noncontingent reinforcers during extinction) lead
      to greater persistence of the procurement response. A third set of studies
      analyzed the contextual control and relapse of chained behaviors. The context
      controls both the acquisition and extinction of chained behaviors. In addition, a
      separately-extinguished consumption response is renewed when returned to the
      context of the chain. The research expands our general understanding of the
      learning processes that govern instrumental behavior as well as our understanding
      of chains.

PMID- 28449948
TI  - Sunitinib specifically augments glucose-induced insulin secretion.
AB  - The tyrosine kinase inhibitor sunitinib is used for the treatment of numerous
      cancers in humans. In diabetic patients, sunitinib lowers blood glucose levels
      and improves glycaemic control. This study aims to analyse whether sunitinib has
      specific and direct effects on insulin secreting beta-cells. Regulation of
      insulin secretion, of cellular cAMP levels and activation of signalling pathways
      were examined upon exposure of rat insulinoma INS-1E cells to sunitinib under
      specific stimulatory and inhibitory conditions. Secreted insulin and cellular
      cAMP levels were measured using RIA and ELISA, respectively. Protein
      phosphorylations were examined on western blots. Sunitinib enhanced glucose
      induced insulin secretion (GIIS) concentration-dependently, reaching a maximal
      stimulation at 2MUM. Sunitinib further augmented insulin secretion in the
      presence of elevated cAMP levels and the FFAR1 agonists. Adrenaline and the PKA
      inhibitor H89 counteracted the stimulatory effect of sunitinib on secretion.
      However, sunitinib altered neither the cellular levels of cAMP nor the
      phosphorylation of PKA. Sunitinib did not reduce IGF-1-induced phosphorylation of
      AKT/PKB and ERK1/2. In conclusion, these results suggest that sunitinib
      stimulates GIIS by a direct effect on beta-cells, which may contribute to the
      glucose-lowering action of the tyrosine kinase inhibitor in humans.

PMID- 28449949
TI  - Energetic and environmental assessment of thermochemical and biochemical ways for
      producing energy from agricultural solid residues: Coffee Cut-Stems case.
AB  - Forest residues are an important source of biomass. Among these, Coffee Cut-Stems
      (CCS) are an abundant wood waste in Colombia obtained from coffee crops
      renovation. However, only low quantities of these residues are used directly in
      combustion processes for heating and cooking in coffee farms where their energy
      efficiency is very low. In the present work, an energy and environmental
      assessment of two bioenergy production processes (ethanol fermentation and
      gasification) using CCS as raw material was performed. Biomass gasification seems
      to be the most promising thermochemical method for bioenergy production whereas,
      ethanol fermentation is a widely studied biochemical method to produce biofuels.
      Experimental runs of the CCS gasification were carried out and the synthesis gas
      composition was monitored. Prior to the fermentation process, a treatment of the
      CCS is required from which sugar content was determined and then, in the
      fermentation process, the ethanol yield was calculated. Both processes were
      simulated in order to obtain the mass and energy balance that are used to assess
      the energy efficiency and the potential environmental impact (PEI). Moderate high
      energy efficiency and low environmental impacts were obtained from the CCS
      gasification. In contrast, high environmental impacts in different categories and
      low energy efficiencies were calculated from the ethanolic fermentation. Biomass
      gasification seems to be the most promising technology for the use of Coffee Cut
      Stems with high energy yields and low environmental issues.

PMID- 28449950
TI  - The imperative for emergency medicine to create its own alternative payment
      model.
AB  - Seven years after the Affordable Care Act legislated Alternative Payment Models,
      it is time for Emergency Medicine to find its place within this value-based trend
      by developing its own Alternative Payment Model.

PMID- 28449951
TI  - Inspiratory Muscle Function and Exercise Capacity in Patients With Heart Failure
      With Preserved Ejection Fraction.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a clinical
      syndrome characterized by impaired exercise capacity resulting from dyspnea and
      fatigue. The pathophysiological mechanisms underlying the exercise intolerance in
      HFpEF are not well established. We sought to evaluate the effects of inspiratory
      muscle function on exercise tolerance in symptomatic patients with HFpEF. METHODS
      AND RESULTS: A total of 74 stable symptomatic patients with HFpEF and New York
      Heart Association class II-III underwent a cardiopulmonary exercise test between
      June 2012 and May 2016. Inspiratory muscle weakness was defined as maximum
      inspiratory pressure (MIP)  <70% of normal predicted values. Pearson correlation
      coefficient and multivariate linear regression analysis were used to assess the
      association between percent of predicted MIP (pp-MIP) and maximal exercise
      capacity [measured by peak oxygen uptake (peak VO2) and percent of predicted peak
      VO2 (pp-peak VO2)]. Thirty-one patients (42%) displayed inspiratory muscle
      weakness. Mean (standard deviation) age was 72.5 +/- 9.1 years, 53% were women,
      and 35.1% displayed New York Heart Association class III. Mean peak VO2 and pp
      peak VO2 were 10 +/- 2.8 mL*min*kg and 57.3 +/- 13.8%, respectively. The median
      (interquartile range) of pp-MIP was 72% (58%-90%). pp-MIP was not correlated with
      peak VO2 (r = -0.047, P = .689) nor pp-peak VO2 (r = -0.078, P = .509).
      Furthermore, in multivariable analysis, pp-MIP showed no association with peak
      VO2 (beta coefficient = 0.01, 95% confidence interval -0.01 to 0.03, P = .241)
      and pp-peak VO2 (beta coefficient = -0.00, 95% confidence interval -0.10 to 0.10,
      P = .975). CONCLUSIONS: In symptomatic elderly patients with HFpEF, we found that
      pp-MIP was not associated with either peak VO2 or pp-peak VO2.

PMID- 28449947
TI  - Barcoding of GPCR trafficking and signaling through the various trafficking
      roadmaps by compartmentalized signaling networks.
AB  - Proper signaling by G protein coupled receptors (GPCR) is dependent on the
      specific repertoire of transducing, enzymatic and regulatory kinases and
      phosphatases that shape its signaling output. Activation and signaling of the
      GPCR through its cognate G protein is impacted by G protein-coupled receptor
      kinase (GRK)-imprinted "barcodes" that recruit beta-arrestins to regulate
      subsequent desensitization, biased signaling and endocytosis of the GPCR. The
      outcome of agonist-internalized GPCR in endosomes is also regulated by sequence
      motifs or "barcodes" within the GPCR that mediate its recycling to the plasma
      membrane or retention and eventual degradation as well as its subsequent
      signaling in endosomes. Given the vast number of diverse sequences in GPCR,
      several trafficking mechanisms for endosomal GPCR have been described. The
      majority of recycling GPCR, are sorted out of endosomes in a "sequence-dependent
      pathway" anchored around a type-1 PDZ-binding module found in their C-tails. For
      a subset of these GPCR, a second "barcode" imprinted onto specific GPCR
      serine/threonine residues by compartmentalized kinase networks was required for
      their efficient recycling through the "sequence-dependent pathway". Mutating the
      serine/threonine residues involved, produced dramatic effects on GPCR
      trafficking, indicating that they played a major role in setting the trafficking
      itinerary of these GPCR. While endosomal SNX27, retromer/WASH complexes and actin
      were required for efficient sorting and budding of all these GPCR, additional
      proteins were required for GPCR sorting via the second "barcode". Here we will
      review recent developments in GPCR trafficking in general and the human beta1
      adrenergic receptor in particular across the various trafficking roadmaps. In
      addition, we will discuss the role of GPCR trafficking in regulating endosomal
      GPCR signaling, which promote biochemical and physiological effects that are
      distinct from those generated by the GPCR signal transduction pathway in
      membranes.

PMID- 28449952
TI  - Heart Transplantation in Giant Cell Myocarditis: Analysis of the United Network
      for Organ Sharing Registry.
AB  - BACKGROUND: Giant cell myocarditis (GCM) is a lethal, rapidly progressive
      disease, for which heart transplantation is the treatment of choice. We sought to
      describe the characteristics and outcomes of patients with GCM who undergo heart
      transplantation. METHODS AND RESULTS: We used the United Network for Organ
      Sharing thoracic organ transplantation registry to identify adults with GCM as
      the primary diagnosis and compared their characteristics and outcomes with
      patients who underwent transplantation for other types of myocarditis and for
      idiopathic dilated cardiomyopathy (IDCMP). A total of 32 patients with GCM were
      compared with 219 patients with myocarditis and 14,221 patients with IDCMP.
      Median age at listing for GCM was 52 years (interquartile range 40-55 y), and the
      majority were white (94%), male (63%), and listed as 1A (44%). Biventricular
      assist devices were used more frequently in GCM compared with IDCMP (31% vs 2%; P
      < .001). After transplantation, there were no statistically significant
      differences among GCM, myocarditis, and IDCMP patients regarding pacemaker
      implantation, dialysis initiation, or stroke rate. GCM patients had increased
      risk of acute rejection compared with IDCMP patients (16% vs 5.0%; P = .021) but
      no difference in rehospitalization for rejection among the 3 etiologies (P =
      .88). The cumulative survivals for GCM patients at 1, 5, and 10 years were 94%,
      82%, and 68%, respectively, which was similar to the other etiologies (P = .11).
      CONCLUSIONS: Compared with patients with IDCMP, those with GCM present more
      acutely and have significantly higher utilization of biventricular mechanical
      circulatory support. Despite higher rates of early rejection, post
      transplantation survival of patients with GCM was similar to that of other
      myocarditides and IDCMP.

PMID- 28449953
TI  - Detection of colonization by carbapenem-resistant organisms by real-time
      polymerase chain reaction from rectal swabs in patients with chronic renal
      disease.
AB  - BACKGROUND: Carbapenem-resistant organism (CRO) colonization is a serious problem
      that increases the risk of infection and contributes to dissemination of
      antimicrobial resistance in healthcare-associated environments. The risk of
      acquisition and dissemination of CRO is high in chronic renal failure patients
      and the surveillance culture is recommended as a component of infection control
      programmes. AIM: To assess colonization by CRO, comparing phenotypic and
      molecular-based methods of diagnostics, in rectal swabs in a large population of
      chronic renal failure patients. METHODS: A total of 1092 rectal swabs (ESwabTM)
      were collected at two different times from 546 chronic kidney disease (CKD)
      patients from a specialized tertiary care university centre. They were divided
      into three groups: conservative treatment (N = 129), dialysis (N = 217), and
      transplanted patients (N = 200). A chromogenic (CHROMagarTM) KPC agar and the
      multiplex real-time polymerase chain reaction (qPCR) targeting carbapenemase
      encoding genes were tested as phenotypic and molecular screening for
      carbapenemase production. Matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry and conventional PCR were also performed on the isolates
      grown on chromogenic agar. FINDINGS: Among the 1092 samples, 150 (13.7%) were
      identified as CRO producers according to chromogenic agar. Only 26 (2.4%) were
      confirmed as KPC by conventional PCR. According to qPCR direct from swab, 31
      (2.8%) were positive for KPC, 39 (3.6%) for GES, and three (0.3%) for SPM with
      kappa index of 0.256. CONCLUSION: The qPCR technique provides faster results when
      compared to culture method and enables rapid implementation of control measures
      and interventions to reduce the spread of CRO in healthcare settings, especially
      among CKD patients.

PMID- 28449954
TI  - The immunomodulatory protein RH36 is relating to blood-feeding success and
      oviposition in hard ticks.
AB  - An immunomodulatory protein designated RH36 was identified in the tick
      Rhipicephalus haemaphysaloides. The cDNA sequence of RH36 has 844bp and encodes a
      deduced protein with a predicted molecular weight of 24kDa. Bioinformatics
      analysis indicated that RH36 presented a degree of similarity of 34.36% with the
      immunomodulatory protein p36 from the tick Dermacentor andersoni. The recombinant
      RH36 (rRH36) expressed in Sf9 insect cells suppressed the T-lymphocyte mitogen
      driven in vitro proliferation of splenocytes and the expression of several
      cytokines such as IL-2, IL-12, and TNF-alpha. Furthermore, the proliferation of
      splenocytes isolated from rRH36-inoculated mice was significantly lower than that
      in control mice, suggesting that rRH36 could directly suppress immune responses
      in vivo. In addition, microarray analysis of splenocytes indicated that the
      expression of several immunomodulatory genes was downregulated by rRH36. The
      silencing of the RH36 gene by RNAi led to a 37.5% decrease in the tick attachment
      rate 24h after placement into the rabbit ears, whereas vaccination with RH36
      caused a 53.06% decrease in the tick engorgement rate. Unexpectedly, RNAi induced
      a significant decrease in the oviposition rate, ovary weight at day 12 after
      engorgement, and egg-hatching rate. The effects of RH36 on blood feeding and
      oviposition were further confirmed by vaccination tests using the recombinant
      protein. These results indicate that RH36 is a novel member of immunosuppressant
      proteins and affects tick blood feeding and oviposition.

PMID- 28449955
TI  - Predictors of induction onto extended-release naltrexone among unemployed heroin
      dependent adults.
AB  - BACKGROUND AND AIM: Extended-release naltrexone (XR-NTX) blocks the effects of
      opioids for 4weeks; however, starting treatment can be challenging because it
      requires 7 to 10days of abstinence from all opioids. In the present study we
      identified patient and treatment characteristics that were associated with
      successful induction onto XR-NTX. METHODS: 144 unemployed heroin-dependent adults
      who had recently undergone opioid detoxification completed self-report measures
      and behavioral tasks before starting an outpatient XR-NTX induction procedure.
      Employment-based reinforcement was used to promote opioid abstinence and
      adherence to oral naltrexone during the induction. Participants were invited to
      attend a therapeutic workplace where they earned wages for completing jobs skills
      training. Participants who had used opioids recently were initially invited to
      attend the workplace for a 7-day washout period. Then those participants were
      required to provide opioid-negative urine samples and then take scheduled doses
      of oral naltrexone to work and earn wages. Participants who had not recently used
      opioids could begin oral naltrexone immediately. After stabilization on oral
      naltrexone, participants were eligible to receive XR-NTX and were randomized into
      one of four treatment groups, two of which were offered XR-NTX. Binary and
      multiple logistic regressions were used to identify characteristics at intake
      that were associated with successfully completing the XR-NTX induction. RESULTS:
      58.3% of participants completed the XR-NTX induction. Those who could begin oral
      naltrexone immediately were more likely to complete the induction than those who
      could not (79.5% vs. 25.0%). Of 15 characteristics, 2 were independently
      associated with XR-NTX induction success: legal status and recent opioid
      detoxification type. Participants who were not on parole or probation (vs. on
      parole or probation) were more likely to complete the induction (OR [95% CI]=2.5
      [1.1-5.7], p=0.034), as were those who had come from a longer-term detoxification
      program (>=21days) (vs. a shorter-term [<21days]) (OR [95% CI]=7.0 [3.0-16.6],
      p<0.001). CONCLUSIONS: Our analyses suggest that individuals recently leaving
      longer-term opioid detoxification programs are more likely to complete XR-NTX
      induction. Individuals on parole or probation are less likely to complete XR-NTX
      induction and may need additional supports or modifications to induction
      procedures to be successful.

PMID- 28449956
TI  - Implicit vs. explicit dimensions of guilt and dominance in criminal psychopathy.
AB  - The current study investigated the relationship between psychopathy and two
      concepts that hold a central position in conceptualizations of this disorder,
      being guilt and dominance. Both constructs were measured using explicit measures
      (i.e., self-report), as well as indirect assessment (i.e., the Single Category
      Implicit Association Test; Sc-IAT). Our sample consisted of 43 psychopathic
      offenders, 42 nonpsychopathic offenders, and 26 nonoffender controls. Although no
      overall group differences emerged, the lifestyle/antisocial traits of psychopathy
      (Factor 2) predicted reduced self-reported guilt on a dimensional level. As
      hypothesized, such a relationship was absent for the interpersonal/affective
      dimension of psychopathy (Factor 1). Psychopathy was unrelated to implicit self
      guilt associations. Regarding dominance, psychopathy was not significantly
      associated with indirectly or explicitly assessed dominance. These findings are
      interpreted in the light of empirical knowledge on moral emotions, insight and
      response distortion in highly antisocial offenders.

PMID- 28449957
TI  - Assessment of Breast Asymmetry in Adolescent Idiopathic Scoliosis Using an
      Automated 3D Body Surface Measurement Technique.
AB  - STUDY DESIGN: Cohort study. OBJECTIVES: To assess breast asymmetry (BA) directly
      with 3D surface imaging and to validate it using MRI values from a cohort of 30
      patients with significant adolescent idiopathic scoliosis (AIS). Also, to study
      the influence of posture (prone vs standing) on BA using the automated method on
      both modalities. SUMMARY OF BACKGROUND DATA: BA is a common concern in young
      female patients with AIS. In a previous study using MRI, we found that the
      majority of patients with significant AIS experienced BA of up to 21% in addition
      to their chest wall deformity. MRI is costly and not always readily available. 3D
      surface topography, which offers fast and reliable breast acquisitions without
      radiation or distortion of the body surface, is an alternative method in the
      clinical setting. METHODS: Thirty patients with AIS were enrolled in the study on
      the basis of their thoracic curvature, skeletal and breast maturity, without
      regard to their perception of their BA. Each patient underwent two imaging
      studies of their torso: a 3D trunk surface topography and a breast MRI. An
      automated breast volume measuring method was proposed using a program developed
      with Matlab programming. RESULTS: Strong correlations were obtained when
      comparing the proposed method to the MRI on the left breast volumes (LBV) (r =
      0.747), the right breast volumes (RBV) (r = 0.805) and the BA (r = 0.614). Using
      the same method on both imaging modalities also yielded strong correlation
      coefficients on the LBV (r = 0.896), the RBV (r = 0.939) and the BA (r = 0.709).
      CONCLUSIONS: The proposed 3D body surface automated measurement technique is
      feasible clinically and correlates very well with breast volumes measured using
      MRI. Additionally, breast volumes remain comparable despite being measured in
      different body positions (standing and prone) in a young cohort of AIS patients.
      LEVEL OF EVIDENCE: Level IV.

PMID- 28449958
TI  - Predicting 3D Thoracic Kyphosis Using Traditional 2D Radiographic Measurements in
      Adolescent Idiopathic Scoliosis.
AB  - STUDY DESIGN: Retrospective. OBJECTIVE: To develop and validate a prediction
      formula to estimate three-dimensional (3D) T5-T12 kyphosis in adolescent
      idiopathic scoliosis (AIS) from standard two-dimensional (2D) radiographic
      measurements. SUMMARY OF BACKGROUND DATA: 2D measurements of thoracic kyphosis in
      AIS patients overestimate 3D kyphosis; however, there is a lack of widespread
      availability of 3D imaging technology. METHODS: Retrospective review was
      performed for AIS patients with right thoracic curves evaluated with EOS Imaging
      from January 2010 to June 2014. Standard 2D posteroanterior and lateral
      radiographic measurements, pelvic incidence, Nash-Moe grade, Perdriolle rotation,
      and "3D T5-T12" sagittal measures (reconstructed with sterEOS, analyzed with
      custom MatLab code) were input into a multivariate logistic analysis to create a
      prediction model for 3D T5-T12 sagittal alignment. An initial cohort of 66
      patients (curves 14 degrees -85 degrees ) was used to create a predictive model,
      and a separate cohort of 129 patients (curves 16 degrees -84 degrees ) was used
      to validate the formula. RESULTS: 2D thoracic coronal Cobb and 2D T5-T12 kyphosis
      were the only significant predictors in the model. The prediction formula for
      estimating 3D T5-T12 sagittal measurement from standard 2D measurements, in
      degrees, was 18.1 + (0.81*2D T5-T12 sagittal Cobb) - (0.54*2D coronal Cobb), r2 =
      0.84. The average model error between predicted and measured 3D T5-T12 kyphosis
      was +/-7 degrees . The predicted 3D T5-T12 kyphosis (8.6 degrees  +/- 12.1
      degrees ) and measured 3D T5-T12 kyphosis (8.5 degrees  +/- 13.0 degrees ) were
      not significantly different (p = .8). 3D kyphosis was less than standard measures
      of 2D kyphosis (8.5 degrees  +/- 13.0 degrees  vs. 20.2 degrees  +/- 12.6 degrees
      , p < .001). CONCLUSION: This simple validated formula to predict 3D T5-T12
      sagittal alignment using routine 2D thoracic Cobb and T5-T12 kyphosis for
      thoracic AIS patients has great potential value in assessing historical data
      collected prior to the development of 3D imaging methods as well as
      understanding/planning surgical hypokyphosis correction in patients without
      access to 3D imaging.

PMID- 28449959
TI  - Resource Utilization in Adolescent Idiopathic Scoliosis Surgery: Is There
      Opportunity for Standardization?
AB  - INTRODUCTION: Recent healthcare reforms have raised the importance of cost and
      value in the management of disease. Value is a function of benefit and cost.
      Understanding variability in resources utilized by individual surgeons to achieve
      similar outcomes may provide an opportunity for cutting costs though greater
      standardization. The purpose of this study is to evaluate differences in use of
      implants and hospital resources among surgeons performing adolescent idiopathic
      scoliosis (AIS) surgery. METHODS: A multicenter prospective AIS operative
      database was queried. Patients were matched for Lenke curve type and curve
      magnitude, resulting in 5 surgeons and 35 matched groups (N = 175). Mean patient
      age was 14.9 years and curve magnitude 50 degrees . Parameters of interest were
      compared between surgeons via ANOVA and Bonferroni pairwise comparison. RESULTS:
      There was no significant difference in percentage curve correction or levels
      fused between surgeons. Significant differences between surgeons were found for
      percentage posterior approach, operative time, length of stay (LOS), estimated
      blood loss (EBL), cell saver transfused, rod material, screw density, number of
      screws, use of antifibrinolytics, and cessation of intravenous analgesics.
      Despite differences in EBL and cell saver transfused, there were no differences
      in allogenic blood (blood bank) use. CONCLUSION: Significant variability in
      resource utilization was noted between surgeons performing AIS operations,
      although radiographic results were uniform. Standardization of resource
      utilization and cost containment opportunities include implant usage, rod
      material, LOS, and transition to oral analgesics, as these factors are the
      largest contributors to cost in AIS surgery.

PMID- 28449960
TI  - Evaluating the Change in Axial Vertebral Rotation Following Thoracoscopic
      Anterior Scoliosis Surgery Using Low-Dose Computed Tomography.
AB  - BACKGROUND CONTEXT: In recent years, there has been increasing appreciation of
      the need to treat scoliosis as a three-dimensional deformity. PURPOSE: Assessment
      of surgical strategies and outcomes should consider not only the coronal plane
      correction but also derotation of the transverse plane deformity that can affect
      trunk appearance. STUDY DESIGN: This study included a cohort of 29 female
      adolescent idiopathic scoliosis patients who received thoracoscopic single rod
      anterior fusion (TASF) surgery. This study used pre- and postoperative low-dose
      computed tomographic (CT) scans to accurately measure apical axial vertebral
      rotation (AVR). METHODS: The pre- and postoperative values for clinically
      measured coronal Cobb correction and rib hump correction as well as AVR were
      compared to determine whether these values improved postoperatively. There are no
      conflicts of interest to report for authors of this investigation. RESULTS: As
      expected, statistically significant reductions in coronal Cobb angle (mean
      preoperative Cobb 51 degrees , reducing to 24 degrees  at the two-year follow-up)
      and rib hump (mean preoperative rib hump 15 degrees , reducing to 7 degrees  at
      two-year follow-up) were achieved. The mean reduction in apical AVR measured
      using CT was only 3 degrees  (mean preoperative AVR 16 degrees , reducing to 13
      degrees  at two-year follow-up), which was statistically but not clinically
      significant. Significant correlations were found between Cobb angle and rib hump,
      between Cobb angle and AVR, and between AVR and rib hump, suggesting that
      patients with greater coronal Cobb correction also achieve better derotation with
      this surgical procedure. CONCLUSIONS: The historical low-dose CT data set
      permitted detailed three-dimensional assessment of the deformity correction that
      is achieved using thoracoscopic anterior spinal fusion for progressive adolescent
      idiopathic scoliosis.

PMID- 28449961
TI  - Risk Factors of Proximal Junctional Kyphosis in Adolescent Idiopathic Scoliosis
      The Pelvis and Other Considerations.
AB  - STUDY DESIGN: Prospective multicenter database study. OBJECTIVES: To assess the
      incidence of proximal junctional kyphosis (PJK) in operative adolescent
      idiopathic scoliosis (AIS) using contemporary surgical techniques and to identify
      risk factors for PJK. SUMMARY OF BACKGROUND DATA: The incidence of PJK has been
      reported as high as 46% in AIS. Factors associated with PJK have been
      incompletely explored. METHODS: Prospectively enrolled 851 AIS patients (2000
      2011, 78.5% female, average 14.4 years) were evaluated 2 years postoperatively.
      Radiographic and sagittal spinopelvic parameters and rod contour angle (RCA), a
      new measure that reflects the proximal contouring of the rod, were independently
      evaluated for association with PJK based on Lenke type. Multivariate logistic
      regression with backward elimination was performed to identify risk factors for
      PJK. RESULTS: Overall PJK incidence was 7.05% and varies based on Lenke type
      (Lenke 1, 6.35%; Lenke 2 and 4, 4.39%; Lenke 3 and 6, 11.64%; and Lenke 5, 8.49%;
      p = .06). Among patients with Lenke 1 curves, risk factors for PJK were loss of
      kyphosis after surgery, and stopping caudal to the upper end vertebra (UEV). The
      risk of developing PJK increases by 7.1% with each lost degree of kyphosis
      compared with preoperation that occurs after the instrumentation is placed. For
      Lenke 2 and 4 curves, loss of kyphosis and more lordotic (negative) RCA were risk
      factors for PJK. For Lenke 3 and 6 curves, larger preoperative T5-T12 kyphosis
      was the only significant risk factor for PJK. Upper instrumented vertebra (UIV)
      at or cephalad to the UEV was associated with increased risk of PJK in Lenke 5
      curves, which was contrary to the finding for Lenke 1 curves. No significant
      correlation was found between sagittal pelvic parameters and developing PJK.
      CONCLUSION: The incidence of PJK in patients after surgery for AIS is 7.05% and
      varies based on Lenke type. Loss of kyphosis, larger preoperative kyphosis, UIV
      caudal to the proximal UEV (Lenke 1), UIV at or cephalad to the UEV (Lenke 5),
      and decreased RCA were the major risk factors for PJK in AIS. LEVEL OF EVIDENCE:
      Level II.

PMID- 28449962
TI  - Posterior Versus Three-Column Osteotomy for Late Correction of Residual Coronal
      Deformity in Patients With Previous Fusions for Idiopathic Scoliosis.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To compare the early results
      of posterior column (PCO) and three-column (3CO) osteotomies performed in
      patients with previously fused idiopathic scoliosis and review their abilities to
      achieve coronal correction of residual deformities. SUMMARY OF BACKGROUND DATA:
      Residual deformity of previously fused AIS can accelerate adjacent segment
      degeneration secondary to lowest instrumented vertebra (LIV) tilt and rotation.
      Many of these patients are not satisfied with their cosmetic appearance and would
      choose revising the deformity when future surgery is indicated. METHODS: The data
      from 29 consecutive patients who underwent PCOs or 3COs for late revisions of
      idiopathic scoliosis were reviewed. Measurements included Cobb angle, focal
      osteotomy angle, and coronal balance. Perioperative data, complications, and
      patient-reported outcomes were also reviewed. RESULTS: Fourteen patients were
      treated with PCOs and 15 with 3COs. Global coronal correction was equal between
      the two groups. In the PCO group, where patients underwent a mean of 2.4
      osteotomies, 20.2 degrees  of correction was obtained compared to 19.5 degrees 
      in the 3CO group (p = .33), which all underwent single osteotomies. The average
      coronal correction was 9.2 degrees /osteotomy for the PCO group and 14.1 degrees
      /osteotomy for the 3CO group (p < .01). Estimated blood loss was 1,417.5 mL in
      the PCO group compared to 3,199.3 in the 3CO group (p < .01). Five patients (36%)
      had intraoperative complications in the PCO group compared to 12 (80%) in the 3CO
      group (p < .05). There were no differences in operative times, length of stay, or
      patient-reported outcomes between groups. CONCLUSION: PCOs and 3COs performed in
      patients with previously fused spines for idiopathic scoliosis are effective in
      achieving residual deformity correction. In cases of posterior fusions, where the
      patient has a mobile anterior column, PCOs should be considered over 3COs because
      of their decreased risk of blood loss and complications.

PMID- 28449963
TI  - Sequential Magnetic Resonance Imaging Reveals Individual Level Deformities of
      Vertebrae and Discs in the Growing Scoliotic Spine.
AB  - STUDY DESIGN: The aim of this study was to measure contributions of individual
      vertebra and disc wedging to coronal Cobb angle in the growing scoliotic spine
      using sequential magnetic resonance imaging (MRI). Clinically, the Cobb angle
      measures the overall curve in the coronal plane but does not measure individual
      vertebra and disc wedging. It was hypothesized that patients whose deformity
      progresses will have different patterns of coronal wedging in vertebrae and discs
      to those of patients whose deformities remain stable. METHODS: A group of
      adolescent idiopathic scoliosis (AIS) patients each received two to four MRI
      scans (spaced 3-12 months apart). The coronal plane wedge angles of each vertebra
      and disc in the major curve were measured for each scan, and the proportions and
      patterns of wedging in vertebrae and discs were analyzed for subgroups of
      patients whose spinal deformity did and did not progress during the study period.
      RESULTS: Sixteen patients were included in the study; the mean patient age was
      12.9 years (standard deviation 1.7 years). All patients were classified as right
      sided major thoracic Lenke Type 1 curves (9 type 1A, 4 type 1B, and 3 type 1C).
      Cobb angle progression of >=5 degrees  between scans was seen in 56% of patients.
      Although there were measurable changes in the wedging of individual vertebrae and
      discs in all patients, there was no consistent pattern of deformity progression
      between patients who progressed and those who did not. The patterns of
      progression found in this study did not support the hypothesis of wedging
      commencing in the discs and then transferring to the vertebrae. CONCLUSION:
      Sequential MRI data showed complex patterns of deformity progression. Changes to
      the wedging of individual vertebrae and discs may occur in patients who have no
      increase in Cobb angle; therefore, the Cobb method alone may be insufficient to
      capture the complex mechanisms of deformity progression.

PMID- 28449964
TI  - Recurrence of Deep Surgical Site Infection in Cerebral Palsy After Spinal Fusion
      Is Rare.
AB  - STUDY DESIGN: Retrospective review of prospective registry. OBJECTIVES: To assess
      the following in children with cerebral palsy (CP) who develop deep surgical site
      infection (DSSI) after spinal fusion: (1) rate of infection recurrence after
      treatment; (2) treatments used; (3) radiographic outcomes; and (4) differences in
      Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)
      scores versus those of children with no infection (NI). SUMMARY OF BACKGROUND
      DATA: Studies show high rates of surgical site infection in patients with CP but
      do not address late recurrence or quality-of-life effects. METHODS: One hundred
      fifty-one children with CP underwent spinal fusion surgery from 2008 through 2011
      and had >=2-year follow-up. Patients who developed DSSI were compared with
      patients with NI. Student t tests were used to analyze deformity; analysis of
      variance was used to analyze CPCHILD scores in both groups preoperatively and at
      final follow-up. RESULTS: Eleven patients developed DSSI. Causative organisms
      were polymicrobial infection (5 cases), Escherichia coli (2 cases), and Proteus
      mirabilis, Staphylococcus aureus, Enterococcus faecalis, and Peptostreptococcus
      (1 case each). All patients underwent irrigation and debridement and received at
      least 6 weeks of antibiotics. Six had negative-pressure-dressing-assisted wound
      closure; 5 had primary closure. At mean 4-year follow-up (range, 3-5 years) no
      patient had recurrent infection. From immediate postoperative to final follow-up,
      no patient had significant loss of coronal curve (p = .77) or pelvic obliquity (p
      = .71) correction. However, at final follow-up, comfort and emotions, overall
      quality-of-life, and total CPCHILD scores in the DSSI group were significantly
      lower compared with the NI group (p = .005, .022, and .026, respectively).
      CONCLUSIONS: In children with CP who developed DSSI after spinal fusion, there
      was no recurrence of infection or deformity after infection treatment. CPCHILD
      scores in patients with DSSI were lower compared with the NI group.

PMID- 28449965
TI  - Comparison of a Newer Versus Older Protocol for Circumferential Minimally
      Invasive Surgical (CMIS) Correction of Adult Spinal Deformity (ASD)-Evolution
      Over a 10-Year Experience.
AB  - STUDY DESIGN: Retrospective. OBJECTIVES: Compare circumferential minimally
      invasive surgical (CMIS) correction outcomes of patients treated for adult spinal
      deformity (ASD) with a newer versus older protocol SUMMARY OF BACKGROUND DATA:
      CMIS techniques have become increasingly popular. Increasing experience and
      learning curve may help improve outcomes. METHODS: A prospectively collected
      database was queried for all patients who underwent CMIS correction of ASD (Cobb
      angle >20 degrees  or sagittal vertical axis [SVA] >50 mm or pelvic incidence
      lumbar lordosis mismatch >10) at 3+ levels. Those without a full-length
      radiograph or 2-year follow-up were excluded. Patients were compared based on
      treatment using our original or newer protocol. RESULTS: The original protocol
      had 76 patients with an average age of 66.99 years (range 46-81, standard
      deviation [SD] 9.03), and the new protocol had 53 patients with average age of
      65.85 years (range 48-85, SD 8.08). Preoperative and latest visual analog scale
      (VAS) scores in the original were 6.85 and 3.45 (p = .001) and in the new were
      6.19 and 2.27 (p = .004). Delta-VAS scores were 3.27 and 4.27. The Oswestry
      disability index (ODI) reduced from 45.84 to 32.91 (p = .041) in the original and
      from 44.21 to 25.39 (p = .017) in the new. Average delta-ODIs were 22.25 and
      24.01. Preoperative, latest, and delta-SF physical component scores for the
      original were 35.38, 42.42, and 10.06 and for the new, 30.89, 39.49, and 11.93.
      SF mental component scores were 50.96, 55.19, and 12.84 and 50.12, 52.99, and
      8.85. The original and new protocols had latest Cobb angles of 11.54 degrees  and
      11.12 degrees  (p = .789), delta-Cobb angles of 14.51 degrees  and 20.03 degrees 
      (p < .05), latest SVAs of 42.85 and 30.58 mm (p < .05) and latest PI-LL mismatch
      of 15.49 and 9.00 mm (p < .05). In the original and the new, the average
      preoperative SVAs that reliably achieved a postoperative SVA of 50 mm or less
      were 84 and 119 mm, respectively, and the maximum delta-SVAs were 89 and 120 mm.
      The new protocol had fewer surgical complications (p < .05). CONCLUSION:
      Improvements in radiographic scores, functional outcomes, and limits of SVA
      correction and lower complication rates suggest that the new protocol may help
      improve outcomes. These findings may be a reflection of our 10-year experience
      and advances in the learning curve. LEVEL OF EVIDENCE: Level IV.

PMID- 28449966
TI  - Environmental concentrations of cocaine and its main metabolites modulated
      antioxidant response and caused cyto-genotoxic effects in zebrafish embryo cells.
AB  - Illicit drugs have been recently identified as a serious environmental problem
      because of the growing evidence regarding their occurrence in aquatic environment
      and potential toxicity towards non-target organisms. Among them, cocaine (COC)
      and its main metabolites, namely benzoylecgonine (BE) and ecgonine methyl ester
      (EME), are commonly measured in freshwaters worldwide at levels that might cause
      diverse sub-lethal effects to aquatic organisms. Thus, the present study was
      aimed at investigating the potential adverse effects induced by the exposure to
      environmental concentrations (0.04, 0.4, 4 and 40 nM) of COC, BE, and EME on
      zebrafish (Danio rerio) embryos at 96 h post fertilization. Cytotoxicity was
      assessed by the Trypan Blue exclusion method, while primary and fixed genetic
      damages were evaluated by the Single Cell Gel Electrophoresis (SCGE) assay, and
      the DNA diffusion assay together with the Micronucleus test, respectively. The
      involvement of oxidative stress in the mechanism of action (MoA) of all tested
      drugs was assessed by measuring the activity of defense enzymes (SOD, CAT, GPx,
      and GST) and the expression of their encoding genes. Exposure to COC and both
      metabolites significantly reduced cell viability, increased DNA fragmentation and
      promoted the onset of apoptotic cells and micronuclei in zebrafish embryos.
      Results from oxidative stress-related endpoints and gene expression suggested
      that the observed genotoxicity may be caused by an overproduction of free
      radicals that imbalanced the oxidative status of embryos. The integration of
      biomarker responses into a synthetic index showed that at each tested
      concentration, BE and EME had a similar toxicity and were both more toxic than
      COC. Our data confirmed the potential toxicity of environmental concentrations of
      COC, BE, and EME, suggesting the need of further in-depth studies to shed light
      on their MoA and long-term toxicity towards non-target aquatic species.

PMID- 28449967
TI  - Exposure scenario: Another important factor determining the toxic effects of
      PM2.5 and possible mechanisms involved.
AB  - Worsening air pollution is a serious threat to public health in many urban and
      heavily industrialized areas. Particle size and chemical composition are well
      known determinants of the pathological response to air pollution. In addition,
      pathological responses may depend on the exposure profile (or scenario) of air
      pollution. For instance, we previously demonstrated that repeated exposure to low
      levels of fine airborne particulate matter (PM2.5) induced distinct epigenetic
      changes compared to acute high-doses exposure. In the present study, we evaluated
      the differential pathological responses of BEAS-2B human bronchial epithelial
      cells to two distinct PM2.5 exposure scenarios: 24-h exposure to high-doses PM2.5
      (0, 6, 12, 24, 48, 96 MUg/cm2) and 10 days' repeated exposure to low levels of
      PM2.5 (0, 1.5, 3, 6 MUg/cm2). Acute exposure to high concentrations of PM2.5
      caused ROS burst, marked DNA damage, dysfunction of the endoplasmic reticulum
      (ER) stress response, autophagy and necrotic cell death. In contrast, repeated
      low levels of PM2.5 led to sustained low-grade ROS accumulation, milder DNA
      damage, ER stress/unfolded protein response (UPR), S-phase arrest, apoptosis, and
      autophagy. Notably, most cells surviving repeated low-level exposure showed a
      series of abnormal adaptive responses, such as inhibition of mitochondria
      biogenesis and epigenetic dysregulation. These results indicate that different
      PM2.5 exposure scenarios induce distinct forms cytotoxicity and adaptive
      response. In addition to particle size and chemical composition, exposure
      scenario may be a critical factor determining the toxic health effects of PM2.5.

PMID- 28449968
TI  - Ecotoxicological effects of enrofloxacin and its removal by monoculture of
      microalgal species and their consortium.
AB  - Enrofloxacin (ENR), a fluoroquinolone antibiotic, has gained big scientific
      concern due to its ecotoxicity on aquatic microbiota. The ecotoxicity and removal
      of ENR by five individual microalgae species and their consortium were studied to
      correlate the behavior and interaction of ENR in natural systems. The individual
      microalgal species (Scenedesmus obliquus, Chlamydomonas mexicana, Chlorella
      vulgaris, Ourococcus multisporus, Micractinium resseri) and their consortium
      could withstand high doses of ENR (<=1 mg L-1). Growth inhibition (68-81%) of the
      individual microalgae species and their consortium was observed in ENR (100 mg L
      1) compared to control after 11 days of cultivation. The calculated 96 h EC50 of
      ENR for individual microalgae species and microalgae consortium was 9.6-15.0 mg
      ENR L-1. All the microalgae could recover from the toxicity of high
      concentrations of ENR during cultivation. The biochemical characteristics (total
      chlorophyll, carotenoid, and malondialdehyde) were significantly influenced by
      ENR (1-100 mg L-1) stress. The individual microalgae species and microalgae
      consortium removed 18-26% ENR at day 11. Although the microalgae consortium
      showed a higher sensitivity (with lower EC50) toward ENR than the individual
      microalgae species, the removal efficiency of ENR by the constructed microalgae
      consortium was comparable to that of the most effective microalgal species.

PMID- 28449970
TI  - Vaccinating adults with chronic disease: We can do better.

PMID- 28449969
TI  - Association between functional antibody against Group B Streptococcus and
      maternal and infant colonization in a Gambian cohort.
AB  - BACKGROUND: Vertical transmission of Group B Streptococcus (GBS) is a
      prerequisite for early-onset disease and a consequence of maternal GBS
      colonization. Disease protection is associated with maternally-derived anti-GBS
      antibody. Using a novel antibody-mediated C3b/iC3b deposition flow cytometry
      assay which correlates with opsonic killing we developed a model to assess the
      impact of maternally-derived functional anti-GBS antibody on infant GBS
      colonization from birth to day 60-89 of life. METHODS: Rectovaginal swabs and
      cord blood (birth) and infant nasopharyngeal/rectal swabs (birth, day 6 and day
      60-89) were obtained from 750 mother/infant pairs. Antibody-mediated C3b/iC3b
      deposition with cord and infant sera was measured by flow cytometry. RESULTS: We
      established that as maternally-derived anti-GBS functional antibody increases,
      infant colonization decreases at birth and up to three months of life, the
      critical time window for the development of GBS disease. Further, we observed a
      serotype (ST)-dependent threshold above which no infant was colonized at birth.
      Functional antibody above the upper 95th confidence interval for the geometric
      mean concentration was associated with absence of infant GBS colonization at
      birth for STII (p<0.001), STIII (p=0.01) and STV (p<0.001). Increased functional
      antibody was also associated with clearance of GBS between birth and day 60-89.
      CONCLUSIONS: Higher concentrations of maternally-derived antibody-mediated
      complement deposition are associated with a decreased risk of GBS colonization in
      infants up to day 60-89 of life. Our findings are of relevance to establish
      thresholds for protection following vaccination of pregnant women with future GBS
      vaccines.

PMID- 28449971
TI  - Indirect (herd) protection, following pneumococcal conjugated vaccines
      introduction: A systematic review of the literature.
AB  - BACKGROUND: Pneumococcal diseases are major causes of morbidity among adults,
      especially those over 50years of age. While pneumococcal conjugated vaccines
      (PCV's) impact on pneumococcal disease rates among children is well established,
      the extent of its impact on adult pneumococcal related illness remains unclear.
      The aim of this systematic literature review was to describe the impact of PCV
      introduction to childhood national immunization programs worldwide on PCV-naive
      adult population. METHODS: A systematic literature search was performed using the
      PubMed database. The search was limited to articles written in English and
      published between January 2000 and February 2016. Studies evaluating pneumococcal
      disease rates in individuals over 5years of age were included. Independent
      extraction of articles was performed by the two authors. Search terms included:
      Pneumococcal conjugated vaccine, herd, indirect, adults, and pneumonia. RESULTS:
      Forty-nine articles meeting the selection criteria were identified, 39 regarding
      invasive pneumococcal disease (IPD, one on meningitis only), 8 regarding
      pneumonia, and 2 on both IPD and pneumonia. The majority of reports were from the
      US, UK and Canada. Considerable variability in the data sources, quality and
      completeness was observed. While most studies reported either statistically
      significant reduction or insignificant changes in IPD and pneumonia disease rates
      in adults following PCV nationwide implementation, few studies reported
      statistically significant increase in pneumococcal disease rates, these were
      mainly from countries with low PCV coverage rates and/or inadequate surveillance.
      CONCLUSION: Invasive pneumococcal diseases and pneumonia rates among the adult
      population decreased in most countries following PCV introduction into the NIP.
      This indirect effect on older population seems to be dependent on PCV coverage
      rates and time from PCV nationwide implementation. Adults >65years old seem to
      benefit the most from PCV introduction.

PMID- 28449972
TI  - Effect of prophylactic or therapeutic administration of paracetamol on immune
      response to DTwP-HepB-Hib combination vaccine in Indian infants.
AB  - BACKGROUND: Vaccination is considered as the most cost effective method for
      preventing infectious diseases. Low grade fever is a known adverse effect of
      vaccination. In India, it is a common clinical practice to prescribe paracetamol
      either prophylactically or therapeutically to manage fever. Some studies have
      shown that paracetamol interferes with antibody responses following immunization.
      This manuscript reports the outcome of a post hoc analysis of data from a
      clinical trial of a pentavalent vaccine in Indian infants where paracetamol was
      not used or was used either as prophylaxis or for treatment of fever. METHODS:
      Pre and post vaccine antibody levels against Diphtheria, Tetanus, Pertussis,
      Hepatitis B, Haemophilus influenzae type B were assessed in no paracetamol and
      paracetamol groups. The paracetamol group was further divided into prophylactic
      and treatment groups. RESULTS: Similar rates of seroprotection/seroresponse for
      anti-D, anti-T, anti-wP, anti-PT, anti-HBs and anti-PRP were observed in all the
      groups. There was no clear tendency for difference in percentage
      seroprotection/seroresponse and geometric mean (GM) titers in any of the groups.
      CONCLUSION: The study found no evidence that paracetamol usage either as
      prophylactic or for treatment impact immunological responses to DTwP-HepB-Hib
      combination vaccine. [Clinical trial registry of India (study registration number
      CTRI/2012/08/002872)].

PMID- 28449973
TI  - Near real-time surveillance for Guillain-Barre syndrome after influenza
      vaccination among the Medicare population, 2010/11 to 2013/14.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is a serious acute demyelinating
      disease that causes weakness and paralysis. The Food and Drug Administration
      (FDA) began collaborating with the Centers for Medicare and Medicaid Services
      (CMS) to develop near real-time vaccine safety surveillance capabilities in 2006
      and has been monitoring for the risk of GBS after influenza vaccination for every
      influenza season since 2008. METHODS: We present results from the 2010/11 to
      2013/14 influenza seasons using the Updating Sequential Probability Ratio Test
      (USPRT), with an overall 1-sided alpha of 0.05 apportioned equally using a
      constant alpha-spending plan among 20 consecutive weekly tests, 5 ad hoc tests,
      and a 26th final end of season test. Observed signals were investigated using the
      self-controlled risk interval (SCRI) design. RESULTS: Over 15 million people were
      vaccinated in each influenza season. In the 2010/11 influenza season, we observed
      an elevated GBS risk during the season, with an end of season SCRI analysis
      finding a nonsignificant increased risk (RR=1.25, 95% CI: 0.96-1.63). A
      sensitivity analysis applying the positive predictive value of the ICD-9 code for
      GBS from the 2009/10 season estimated a RR=1.98 (95% CI: 1.42-2.76). Although the
      2010/11 influenza vaccine suggested an increased GBS risk, surveillance of the
      identical vaccine in the 2011/12 influenza season did not find an increased GBS
      risk after vaccination. No signal was observed in the subsequent three influenza
      seasons. CONCLUSIONS: Conducting near real-time surveillance using USPRT has
      proven to be an excellent method for near real-time GBS surveillance after
      influenza vaccination, as demonstrated by our surveillance efforts during the
      2010/11-2013/14 influenza seasons. In the 2010/2011 influenza season, in addition
      to the 2009 H1N1 influenza pandemic, using near real-time surveillance we were
      able to observe a signal early in the influenza season and the method has now
      become routine.

PMID- 28449974
TI  - In-hospital acute myocardial infarction: A case of type II Kounis syndrome.
AB  - Kounis syndrome (KS) is the coincidental occurrence of acute coronary syndrome
      (ACS) and anaphylactic or allergic insult. It results from mast cell
      degranulation with subsequent release of numerous inflammatory mediators, leading
      to coronary vasospasm or atheromatous plaque rupture. Diagnosis is clinical and
      based on the temporal relationship between the two events. Despite the growing
      number of reported cases, especially in southern Europe, the lack of awareness of
      this association may lead to under-reporting in Portugal. Recognition of KS, even
      if retrospective, has clinical implications since individual atopy must be
      investigated and desensitization measures should be employed, if possible, to
      prevent future events. We report the case of a 70-year-old man who was admitted
      to hospital because of generalized exanthema and itching and onset of chest pain
      while under observation. Coronary angiography confirmed coronary artery disease
      and ACS and he was diagnosed as having type II KS.

PMID- 28449975
TI  - Study of conicity index, body mass index and waist circumference as predictors of
      coronary artery disease.
AB  - INTRODUCTION AND OBJECTIVE: Obesity is a major risk factor for cardiovascular
      disease. This study was designed to assess whether the conicity index (CI), body
      mass index (BMI) and waist circumference (WC) can be used as predictors of
      coronary artery disease (CAD) and mortality in a middle-aged population of the
      north-western region of Rio Grande do Sul, Brazil. METHODS: This was a
      retrospective, longitudinal cohort study, based on the medical records of
      patients seen in a cardiology institution in a rural area of Rio Grande do Sul.
      The sample consisted of 2396 individuals. The primary endpoint was diagnosis of
      CAD, with mortality as the secondary endpoint. CI, BMI and WC were assessed using
      logistic regression, Cox regression and receiver operating characteristic curve
      analysis. RESULTS: The study showed that none of the anthropometric measures
      could be considered independent factors for either a diagnosis of CAD or
      mortality. Female gender was associated with a significantly lower risk of CAD
      (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.22-0.44), as was absence
      of diabetes (OR: 0.52; 95% CI: 0.33-0.82), while there was a significantly higher
      risk of mortality associated with the presence of CAD (OR: 3.56; 95% CI: 2.00
      6.32) and alcohol consumption (OR: 3.55; 95% CI: 1.60-7.90). CONCLUSIONS: These
      anthropometric measures were not independent predictive factors for CAD diagnosis
      or mortality in a population in southern Brazil. Our results support the
      conclusion that determination of CI, BMI and WC alone is insufficient to assess
      the risk of CAD and mortality in the general population.

PMID- 28449976
TI  - Erratum to "Diagnosis of paradoxical low-flow/low-gradient aortic stenosis: A
      complex process!" [Arch. Cardiovasc. Dis. (2017) 135-8].

PMID- 28449977
TI  - Editorial Comment.

PMID- 28449978
TI  - Author Reply.

PMID- 28449979
TI  - Morphological, molecular and phylogenetic analyses of Diplotriaena bargusinica
      Skrjabin, 1917 (Nematoda: Diplotriaenidae).
AB  - The nematode Diplotriaena bargusinica is a bird air sac parasite, and its
      taxonomy is based mainly on morphological and morphometric characteristics.
      Increasing knowledge of genetic information variability has spurred the use of
      DNA markers in conjunction with morphological data for inferring phylogenetic
      relationships in different taxa. Considering the potential of molecular biology
      in taxonomy, this study presents the morphological and molecular characterization
      of D. bargusinica, and establishes the phylogenetic position of the nematode in
      Spirurina. Twenty partial sequences of the 18S region of D. bargusinica rDNA were
      generated. Phylogenetic trees were obtained through the Maximum Likelihood and
      Bayesian Inference methods where both had similar topology. The group
      Diplotriaenoidea is monophyletic and the topologies generated corroborate the
      phylogenetic studies based on traditional and previously performed molecular
      taxonomy. This study is the first to generate molecular data associated with the
      morphology of the species.

PMID- 28449980
TI  - The effect of submandibular gland preservation during level 1B neck dissection on
      postoperative xerostomia.
AB  - OBJECTIVE: Compare the presence and degree of postoperative xerostomia following
      preservation or excision of the submandibular gland (SMG) during level IB neck
      dissection (ND) without adjuvant radiation. METHODS: Retrospective review with
      patient questionnaire administered to patients with pT1-2N0 oral squamous cell
      carcinoma (SCC) who underwent resection and ND with SMG preservation or SMG
      excision without postoperative radiation from 2011 to 2015. We analyzed an
      additional control group that was age and gender-matched and had not undergone
      oral resection or SMG excision. We compared the scores reported by the three
      groups from three questionnaires: University of Michigan Xerostomia Quality of
      Life (XeQoL), Short Form-8 (SF-8), and a xerostomia severity scale (XSS). Dry
      mouth severity (DMS) was calculated based on XSS scores among those complaining
      of any xerostomia. RESULTS: Eleven SMG preservation group, 14 SMG excision group
      and 15 control group patients completed the survey. Complication and recurrence
      rates were comparable among experimental groups. No differences were identified
      between the two experimental groups for the XeQoL, SF-8, and XSS questionnaires
      (p=0.96, 0.87, 0.7). Control patients reported less xerostomia on XeQoL (p=0.046)
      and XSS (p=0.01) compared to the experimental groups combined with no statistical
      difference in SF-8 scores (p=0.25). No patients in either group developed
      regional recurrence in level IB. CONCLUSION: SMG preservation, though technically
      and oncologically sound, does not appear in this study to reduce xerostomia. Oral
      resection with ND may result in some degree of xerostomia perception.

PMID- 28449981
TI  - Recessive AFG3L2 Mutation Causes Progressive Microcephaly, Early Onset Seizures,
      Spasticity, and Basal Ganglia Involvement.
AB  - BACKGROUND: Mutations in AFG3L2, a gene encoding a subunit of the mitochondrion m
      AAA protease, cause spinocerebellar ataxia type 28 and recessive spastic ataxia
      type 5. Neuroimaging shows cerebellar atrophy. METHODS: Retrospective review of
      the patient charts including their clinical evaluation and molecular genetic,
      neurodiagnostic, and neuroradiological investigations. RESULTS: We describe five
      members of a large consanguineous family with a severe mitochondrial disease
      phenotype in the form of regression of the developmental milestones in the first
      year of life, refractory epilepsy, progressive microcephaly, increased blood
      lactate, basal ganglia involvement, and premature death. Exome sequencing showed
      homozygous mutation of the AFG3L2 gene in all individuals: c.1714G>A
      (p.Ala572Thr). CONCLUSIONS: Our findings add to the phenotypic,
      neuroradiological, genetic, and biochemical spectrum of AFG3L2 mutations.

PMID- 28449982
TI  - Cerebral Developmental Venous Anomaly-Does it Prevent Stroke in Acute Sinus
      Thrombosis?

PMID- 28449983
TI  - Universal Head Ultrasound Screening in Full-term Neonates: A Retrospective
      Analysis of 6771 Infants.
AB  - BACKGROUND: Full-term neonates may have asymptomatic cranial injuries at birth
      and head ultrasound screening could be useful for early diagnosis. The aim of
      this study was to assess the prevalence and type of intracranial abnormalities
      and the usefulness of head ultrasound screening in these infants. METHODS: Head
      ultrasound screening was performed on all full-term neonates (gestational age
      between 37 and 42 weeks), born at Sant'Anna University Hospital of Ferrara,
      Italy, from June 1, 2008 through May 31, 2013. Ultrasound findings were
      categorized into three groups: normal, minor, and major anomalies. RESULTS: All
      full-term neonates (6771) born at our hospital underwent head ultrasound
      screening. One hundred fourteen of 6771 (1.7%) presented ultrasound
      abnormalities, whereas 6657 were normal or exhibited insignificant findings. In
      101 of 114 (88.6%), abnormalities were minor, and only 13 infants had major
      abnormalities (0.19% of all full-term newborns). All neonates with major
      abnormalities presented with either microcephaly or abnormal neurological
      evaluations. Only one individual with major abnormalities was detected
      exclusively by ultrasound. CONCLUSIONS: The number of significant anomalies
      detected by head ultrasound screening in asymptomatic full-term neonates born
      during the study period was low. Therefore, there is no indication for routine
      general head ultrasound screening in these patients. However, even if low, in
      neonates who have neurological abnormalities, risk factors or suspected brain
      malformations, head ultrasound screening may play an important role in the early
      diagnosis of intracranial anomalies.

PMID- 28449984
TI  - Recovery of anthocyanins from residues of Rubus fruticosus, Vaccinium myrtillus
      and Eugenia brasiliensis by ultrasound assisted extraction, pressurized liquid
      extraction and their combination.
AB  - This work investigated the extraction efficiency of polyphenols (anthocyanins)
      from blackberry, blueberry and grumixama residues using combined ultrasonic
      assisted extraction (UAE) and pressurized liquid extraction (PLE) (UAE+PLE). The
      performance of UAE+PLE was compared to those achieved by the isolated PLE and UAE
      methods and conventional Soxhlet extraction. The effects of the extraction
      methods and solvents (acidified water pH 2.0, ethanol+water 50% v/v and
      ethanol+water 70% ethanol v/v) on total phenolics content, anthocyanin
      composition and antioxidant capacity of extracts were investigated by a full
      factorial design. The extraction efficiency for total phenolics and antioxidant
      capacity in decreasing order was: UAE+PLE>PLE~Soxhlet>UAE, and for anthocyanins
      it was: Soxhlet~UAE>UAE+PLE>PLE, using hydroethanolic mixtures as solvents.
      Extractions with acidified water and ultrasound were not effective to recover
      phenolics. Two, four and fourteen anthocyanins were identified in the extracts
      from grumixama, blackberry and blueberry, respectively.

PMID- 28449985
TI  - Encapsulation of fish oil into hollow solid lipid micro- and nanoparticles using
      carbon dioxide.
AB  - Fish oil was encapsulated in hollow solid lipid micro- and nanoparticles formed
      from fully hydrogenated soybean oil (FHSO) using a novel green method based on
      atomization of supercritical carbon dioxide (SC-CO2)-expanded lipid. The highest
      fish oil loading efficiency (97.5%, w/w) was achieved at 50%, w/w, initial fish
      oil concentration. All particles were spherical and in the dry free-flowing form;
      however, less smooth surface with wrinkles was observed when the initial fish oil
      concentration was increased up to 50%. With increasing initial fish oil
      concentration, melting point of the fish oil-loaded particles shifted to lower
      onset melting temperatures, and major polymorphic form transformed from alpha to
      beta and/or beta'. Oxidative stability of the loaded fish oil was significantly
      increased compared to the free fish oil (p<0.05). This innovative method forms
      free-flowing powder products that are easy-to-use solid fish oil formulation,
      which makes the handling and storage feasible and convenient.

PMID- 28449986
TI  - Optimization of milk odd and branched-chain fatty acids analysis by gas
      chromatography using an extremely polar stationary phase.
AB  - Odd and branched-chain fatty acids (OBCFA) are of interest, since they have
      bioactive properties and could be regarded biomarkers of ruminant fat intake. An
      accurate analysis of the individual OBCFA in milk by gas chromatography (GC) is
      not easy due to milk fat complexity. The availability of ionic liquid stationary
      phases as SLB-IL111 can be a useful tool to discriminate OBCFA from other milk FA
      eluting in the same chromatographic regions. The elution behavior of OBCFA on SLB
      IL111 was evaluated based on different GC oven temperature programs. All programs
      assayed discriminated 11:0, iso 13:0, anteiso 13:0, iso 15:0, anteiso 15:0, 15:0
      and iso 17:0. Using an initial temperature of 150 degrees C for 1h, 13:0 and iso
      16:0 were separated from trans-12:1 and 13-14:1, respectively, whereas iso 18:0
      was discriminated from cis-16:1 isomers. 17:0 and 21:0 were well resolved only
      when an initial GC temperature of 160 degrees C was applied.

PMID- 28449987
TI  - Instant coffee as a source of antioxidant-rich and sugar-free coloured compounds
      for use in bakery: Application in biscuits.
AB  - Ammonia caramels are the most common antioxidant colour agent used in bakery
      formulations, although their high sugars content. An alternative could be coffee
      melanoidins, which are brown coloured compounds with antioxidant properties,
      readily available from instant coffee. However, high caffeine content is limiting
      its direct application. To evaluate the possibility of obtaining coloured
      melanoidin-rich, sugars- and caffeine-poor fractions from instant coffee, in this
      work, simple procedures based on their ethanol insolubility (fraction EtPp) or
      retention by ultrafiltration (fraction HWSn) were exploited. Melanoidins
      incorporation into biscuits formulation (amounts of 1, 5 and 10% w/w related to
      flour content) resulted in acceptable coloured products with higher antioxidant
      activity. The biscuits supplemented with 1% EtPp or HWSn had a low caffeine
      content. The caffeine of one espresso coffee was equivalent to 130 biscuits
      containing EtPp and 31 biscuits containing HWSn. Besides, both fractions did not
      promote extra formation of acrylamide or 5-hydroxymethylfurfural during baking.

PMID- 28449988
TI  - Development of antioxidant Pickering high internal phase emulsions (HIPEs)
      stabilized by protein/polysaccharide hybrid particles as potential alternative
      for PHOs.
AB  - We report for the first time the usage of mono-dispersed gliadin/chitosan hybrid
      particles as a particulate emulsifier for Pickering high internal phase emulsions
      (HIPEs) development. The hybrid particles with partial wettability were
      fabricated at pH 5.0 using a facile anti-solvent route. Stable Pickering HIPEs
      with internal phases of up to 83% can be prepared with low particle
      concentrations (0.5-2%). The hybrid latexes were effectively adsorbed and
      anchored at the oil-water interface to exert steric hindrance against
      coalescence. Concomitantly, the compressed droplets in Pickering HIPEs to form a
      percolating 3D-network framework endowed the emulsions viscoelastic and self
      standing features. The protective effect of Pickering HIPEs on curcumin was
      confirmed, and the content of primary oxidation products in HIPEs was slightly
      lower than that in bulk oil. This work opens an attractive strategy to convert
      liquid oils to viscoelastic soft solids without artificial trans fats, as a
      potential alternative for PHOs.

PMID- 28449989
TI  - Identification of the bioactive compounds and antioxidant, antimutagenic and
      antimicrobial activities of thermally processed agro-industrial waste.
AB  - The purpose of the research was to identify the bioactive compounds and to
      evaluate the antioxidant, antimutagenic and antimicrobial activities of the major
      Romanian agro-industrial wastes (apple peels, carrot pulp, white- and red-grape
      peels and red-beet peels and pulp) for the purpose of increasing the wastes'
      value. Each type of waste material was analyzed without (fresh) and with thermal
      processing (10min, 80 degrees C). Based on the obtained results, the thermal
      process enhanced the total phenolic content. The highest antioxidant activity was
      exhibited by thermally processed red-grape waste followed by thermally processed
      red-beet waste. Linoleic acid was the major fatty acid in all analyzed samples,
      but its content decreased significantly during thermal processing. The carrot
      extracts have no antimicrobial effects, while the thermally processed red-grape
      waste has the highest antimicrobial effect against the studied strains. The
      thermally processed red-grape sample has the highest antimutagenic activity
      toward S. typhimurium TA98 and TA100.

PMID- 28449990
TI  - Rapid evaluation of the quality of chestnuts using near-infrared reflectance
      spectroscopy.
AB  - Near-infrared (NIR) diffuse reflectance spectroscopy was used to evaluate the
      quality of fresh chestnuts, which can be affected by mildew, water, and levels of
      water-soluble sugars. The NIR spectra were determined and then modeling was
      performed including principal component analysis - discriminant analysis (PCA
      DA), soft independent modeling of class analogy (SIMCA), linear discriminant
      analysis (LDA), and partial least squares (PLS) methods. LDA model was better
      than PCA-DA model for the discrimination of normal and mildewed chestnuts, and
      the accuracy rates of calibration and validation were 100% and 96.37%,
      respectively. Normal and mildewed chestnuts were easily distinguished by the
      SIMCA classification and showed only 4.7% overlap. A PLS model was established to
      determine the water and water-soluble sugars in chestnuts. The R2 of calibration
      and validation were all higher than 0.9, while the root mean square errors (RMSE)
      were all lower than 0.05, indicating that the established models were successful.

PMID- 28449991
TI  - Evaluation of abamectin, diazinon and chlorpyrifos pesticide residues in apple
      product of Mahabad region gardens: Iran in 2014.
AB  - The purpose of this study was to investigate abamectin, diazinon and chlorpyrifos
      in apple from the Mahabad of Iran. The influences of several parameters including
      shadow and sun, geographical directions and varieties of apples, whether they are
      golden or red type, was also taken into account on the residuals of the
      pesticides in the samples. The results indicated that sun considerably decreased
      the concentrations of diazinon and chlorpyrifos in samples exposed to it.
      Geographical directions are showed to be non-influential on diazinon while they
      are influential on chlorpyrifos ones. This can be attributed to pesticide
      spraying time and prevailing wind direction in Mahabad. The pesticides in golden
      and red varieties showed no significant relations. The apple samples from Mahabad
      did not contain any abamectin while they contained residuals of diazinon and
      chlorpyrifos. In some samples the diazinon and chlorpyrifos were above allowed
      limit according to World Health Organization (WHO) standard.

PMID- 28449992
TI  - Effect of incorporating finger millet in wheat flour on mixolab behavior,
      chapatti quality and starch digestibility.
AB  - Wheat and finger millet flour (two cultivars) were blended in the ratio (3:1) to
      form a composite flour and its dough properties were studied on the mixolab. The
      chapatti making and digestibility behavior of the composite flour was also
      investigated. The wheat finger millet (WFM) flour blend displayed up to 30.7%
      higher total phenolic content (TPC), 38.2% higher total flavonoid content (TFC)
      and 75.4% higher antioxidant activity (AOA) than the wheat flour. Chapattis
      prepared from the composite blends exhibited lower retrogradation as evident by
      the mixolab retrogradation index, higher values of soluble starch and soluble
      amylose in stored chapatti. The slowly digestible starch (SDS) correlated
      positively (R=0.816, p<0.05) with TPC and water absorption correlated positively
      (R=0.995, p<0.05) with damage starch content. The chapattis made from the
      composite flour had higher SDS and resistant starch (RS) values demonstrating
      potential as a food with functional characteristics.

PMID- 28449993
TI  - In vitro peptic digestion of ovomucin-depleted egg white affected by pH,
      temperature and pulsed electric fields.
AB  - The effect of pH (4, 5, 7, and 9) combined with either heat (60, 80 degrees C for
      10min) or pulsed electric fields (PEF) (1.4-1.8kV/cm, 260-690kJ/kg) treatments on
      the in vitro peptic digestion of ovomucin-depleted egg white was investigated.
      Protein digestibility, unaffected by 60 degrees C heating, was increased by
      heating at 80 degrees C, which caused protein aggregation and solution turbidity.
      Compared to ovalbumin and lysozyme, ovotransferrin was more susceptible to
      pepsinolysis. Susceptibility to pepsinolysis of ovalbumin and lysozyme was
      markedly enhanced by heating at 80 degrees C, compared to either 60 degrees C
      heating or PEF processing. MALDI-MS identified proteolytic fragments from
      ovalbumin and lysozyme, exhibiting varied resistance to pepsinolysis. PEF
      processing at ~690kJ/kg and pH 4 increased protein digestibility to a similar
      level to that obtained after heating at 80 degrees C, with negligible solution
      turbidity, showing potential for the production of digestible protein drinks with
      good consumer visual appeal owing to their clarity.

PMID- 28449994
TI  - Phenolic compounds reduce formation of Nepsilon-(carboxymethyl)lysine and
      pyrazines formed by Maillard reactions in a model bread system.
AB  - This study had the objective of determining the antiglycation activity of
      phenolic compounds (PCs) ((+)-catechin, quercetin, gallic, ferulic, and caffeic
      acids) added to a model bread with regards to the inhibition of Nepsilon
      (carboxymethyl)lysine (CML) formation. PCs were found to significantly reduce CML
      (31.77%-87.56%), even at the lowest concentration, with the exception of ferulic
      acid (FA). The strongest inhibitory effect of FA (~62%) appeared when
      concentration was increased to 1.0g/100g of flour. The available lysine losses
      (0.00%-90.51%) showed a significant correlation (0.853-0.990) with effectiveness
      of CML inhibition, except in the case of samples with FA. (+)-Catechin reduced
      CML levels the most, probably due to its structure-antioxidant activity
      relationship, its thermal stability (~51% loss), and its reactivity with epsilon
      lysine side chains (~40.77% loss). Although the bread supplemented with PCs
      contained low levels of CML, this process may adversely affect bread flavor,
      reducing the formation of pyrazines (1.10%-80.77%).

PMID- 28449995
TI  - Melatonin in grapes and grape-related foodstuffs: A review.
AB  - A decade has passed since melatonin was first reported in grapes in 2006. During
      this time, melatonin has not only been found in the berries of most wine grape
      (Vitis vinifera L.) cultivars, but also in most grape-related foodstuffs, e.g.
      wine, grape juice and grape vinegar. In this review, we discuss the melatonin
      content in grapes and grape-related foodstuffs (especially wine) from previous
      studies, the physiological function of melatonin in grapes, and the factors
      contributing to the production of melatonin in grapes and wines. In addition, we
      identify future research needed to clarify the mechanisms of grape melatonin
      biosynthesis and regulation, and establish more accurate analysis methods for
      melatonin in grapes and wines.

PMID- 28449996
TI  - Encapsulation of epigallocatechin gallate in zein/chitosan nanoparticles for
      controlled applications in food systems.
AB  - The objective of this study was to prepare chitosan nanoparticles (CS NPs) coated
      with zein as a promising encapsulation and delivery system for epigallocatechin
      gallate (EGCG). The factors influencing the nanoparticle fabrication, including
      zein concentration, zein/chitosan weight ratio and EGCG encapsulation percentage,
      were systematically investigated. The physicochemical and structural analysis
      showed that the electrostatic interactions and hydrogen bonds were the major
      forces responsible for nanoparticles formation. The transmission electron
      microscopy study revealed the spherical nature with smooth surface of obtained
      nanoparticles. The release profile of EGCG showed a burst effect, followed by
      slow release. EGCG release was relatively higher from zein/chitosan nanoparticles
      (zein/CS NPs) with higher DPPH scavenging activity, than that of NPs without zein
      coating in 95% ethanol fatty simulant. These results indicated that controlled
      release of EGCG from zein/CS NPs and its corresponding antioxidant activities in
      95% ethanol fatty simulant may provide long-term protection against oxidation for
      fatty foods.

PMID- 28449997
TI  - Electrospinning of cyclodextrin/linalool-inclusion complex nanofibers: Fast
      dissolving nanofibrous web with prolonged release and antibacterial activity.
AB  - The volatility and limited water solubility of linalool is a critical issue to be
      solved. Here, we demonstrated the electrospinning of polymer-free nanofibrous
      webs of cyclodextrin/linalool-inclusion complex (CD/linalool-IC-NFs). Three types
      of modified cyclodextrin (HPbetaCD, MbetaCD, and HPgammaCD) were used to
      electrospin CD/linalool-IC-NFs. Free-standing CD/linalool-IC-NFs facilitate
      maximum loading of linalool up to 12% (w/w). A significant amount of linalool (45
      89%) was preserved in CD/linalool-IC-NFs, due to enhancement in the thermal
      stability of linalool by cyclodextrin inclusion complexation. Remarkably,
      CD/linalool-IC-NFs have shown fast-dissolving characteristics in which these
      nanofibrous webs dissolved in water within two seconds. Furthermore, linalool
      release from CD/linalool-IC-NFs inhibited growth of model Gram-negative (E. coli)
      and Gram-positive (S. aureus) bacteria to a great extent. Briefly,
      characteristics of liquid linalool have been preserved in a solid nanofiber form
      and designed CD/linalool-IC-NFs confer high loading capacity, enhanced shelf life
      and strong antibacterial activity of linalool.

PMID- 28449998
TI  - Milk protein isolate (MPI) as a source of dipeptidyl peptidase IV (DPP-IV)
      inhibitory peptides.
AB  - A multifactorial [temperature (40, 50 and 60 degrees C), hydrolysis time (60, 150
      and 240min) and enzyme to substrate ratio (E:S; 1.0, 1.5 and 2.0%)] design of
      experiments (DOE) was used to optimise the release of dipeptidyl peptidase IV
      (DPP-IV) inhibitory peptides during hydrolysis of bovine milk protein isolate
      (MPI) with Neutrase 0.8LTM, yielding 15 hydrolysates (H1-H15). Variation in
      temperature and time had a significant effect on DPP-IV inhibitory properties
      (p<0.05) in contrast with E:S (p>0.05). The DPP-IV half maximal inhibitory
      concentration (IC50) of H4, a potent sample, was maintained following simulated
      gastrointestinal digestion (SGID, DPP-IV IC50=0.60+/-0.06vs. 0.58+/-0.09mgml-1,
      p>0.05). Several peptides with DPP-IV inhibitory features or known activity were
      identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) within
      the hydrolysates. MPI hydrolysates may have potential for use as dietary
      ingredients with serum glucose lowering activity in humans.

PMID- 28449999
TI  - The effects of copper fining on the wine content in sulfur off-odors and on their
      evolution during accelerated anoxic storage.
AB  - Three different red wines with reductive character have been treated with two
      different doses of copper sulfate (0.06 and 0.5mg/L) and with a commercial copper
      containing product at the recommended dose (0.6mg/L). Wines were in contact with
      copper one week, centrifuged and stored at 50 degrees C in strict anoxia for
      2weeks (up to 7 in one case). Brine-releasable (BR-) and free fractions of
      Volatile Sulfur Compounds were determined throughout the process. Relevant
      increases of BR-H2S suggest that those wines contained other H2S precursors non
      detectable by the brine dilution method. Copper treatments had two major effects:
      1) immediate decrease the levels of free H2S and methanethiol (MeSH); 2) slow the
      rate at which free H2S (not MeSH) increases during anoxic storage. After 7weeks
      of anoxia levels of free H2S and MeSH were high and similar regardless of the
      copper treatment. Higher copper doses could induce the accumulation of BR-H2S.

PMID- 28450000
TI  - Investigation of the antioxidant and aldose reductase inhibitory activities of
      extracts from Peruvian tea plant infusions.
AB  - In the present study, the antioxidant and aldose reductase inhibitory activities
      of 24 Peruvian infusion tea plants were investigated by 2,2'-diphenyl-1
      picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
      (ABTS), and aldose reductase assays. Phoradendron sp. showed the highest
      inhibition of aldose reductase (IC50, 1.09+/-0.06MUg/mL) and considerable
      antioxidant (IC50 of DPPH, 58.36+/-1.65MUg/mL; IC50 of ABTS, 9.91+/-0.43MUg/mL)
      effects. In order to identify the antioxidants and aldose reductase inhibitors of
      Phoradendron sp., DPPH-high performance liquid chromatography (HPLC) and
      ultrafiltration-HPLC assays were performed. Chlorogenic acid, 3,5-di-O
      caffeoylquinic acid, and 1,3,5-tri-O-caffeoylquinic acid were identified as the
      antioxidants and aldose reductase inhibitors; apigenin was identified as the
      antioxidant. Finally, Phoradendron sp. and its aldose reductase inhibitors also
      showed a dose-dependent anti-inflammatory effect without cellular toxicity. These
      results suggested that Phoradendron sp. can be a potent functional food
      ingredient as an antioxidant, aldose reductase inhibitor and anti-inflammatory
      agent.

PMID- 28450001
TI  - Optimisation of Pueraria isoflavonoids by response surface methodology using
      ultrasonic-assisted extraction.
AB  - Puerariae Lobatae Radix (PLR) exerts cyto-protective effect against oxidative
      stress due to its high isoflavonoid content. In this study, the ultrasonic
      assisted extraction condition for the maximum recovery of isoflavonoids with high
      cyto-protective effect was optimised by response surface methodology (RSM). A
      second-order polynomial fitted the experimental data (R2: 0.9736; p-value
      <0.0001). The optimal extraction parameters were determined as: extraction time
      16.02min, ethanol concentration 41.41% and liquid-to-solid ratio 44.35mL/g.
      Practical experiments with extraction time 16.00min, ethanol concentration 41.00%
      and liquid-to-solid ratio 44.00mL/g were carried out in triplicate. This
      subsequently yielded a cell viability of 82.90+/-0.78% against hydrogen peroxide
      induced oxidative stress on EA.hy926, and was comparable to the predicted of
      85.60%. Five chemical constituents in the extract were identified to exert cyto
      protective effect. Taken together, this method successfully integrated RSM and
      the partial least squares regression method to optimise the PLR extract with
      highest cyto-protective activity.

PMID- 28450002
TI  - Energy status regulates disease development and respiratory metabolism of
      Lasiodiplodia theobromae (Pat.) Griff. & Maubl.-infected longan fruit.
AB  - Lasiodiplodia theobromae (Pat.) Griff. & Maubl. is a major pathogen causing decay
      of harvested longan fruit. The roles of energy status regulated by 2,4
      dinitrophenol (DNP) and adenosine triphosphate (ATP) in disease development
      regarding respiratory metabolism of L. theobromae-inoculated "Fuyan" longan fruit
      were studied. Compared with L. theobromae-inoculated longans, DNP treatment could
      promote the index of fruit disease, accelerate the decrease in energy charge,
      increase respiration rate and the activities of respiratory terminal oxidases
      like CCO, AAO and PPO, elevate contents of NAD and NADH, but decrease NAD kinase
      activity, as well as contents of NADP and NADPH; however, exogenous ATP supply
      acted contrarily. Above results suggested the different energy status caused by
      DNP and ATP treatments accelerated or delayed the disease development of L.
      theobromae-inoculated longans via regulating Embden-Meyerhof pathway (EMP) and
      tricarboxylic acid (TCA) cycle, pentose phosphate pathway (PPP) and activities of
      respiratory terminal oxidases.

PMID- 28450003
TI  - Protein interactions during flour mixing using wheat flour with altered starch.
AB  - Wheat grain proteins responses to mixing and thermal treatment were investigated
      using Mixolab-dough analysis systems with flour from two cultivars, Ventura-26
      (normal amylose content) and Ventura-19 (reduced amylose content). Size exclusion
      high performance liquid chromatography (SE-HPLC) and two-dimensional gel
      electrophoresis (2-DGE) analysis revealed that, stress associated and metabolic
      proteins largely interacted with dough matrix of Ventura-26 after 26min (56
      degrees C); gliadins, avenin-like b proteins, LMW-GSs, and partial globulins
      showed stronger interactions within the dough matrix of Ventura-26 at 32min/C3
      (80 degrees C), thereafter, however, stronger protein interactions were observed
      within the dough matrix of Ventura-19 at 38min/C4 (85 degrees C) and 43min (80
      degrees C). Thirty-seven proteins associated with changes in dough matrix due to
      reduced amylose content were identified by mass spectrometry and mainly annotated
      to the chromosome group 1, 4, and 6. The findings provide new entry points for
      modifying final product attributes.

PMID- 28450004
TI  - Ultra-high-pressure processing improves proteolysis and release of bioactive
      peptides with activation activities on alcohol metabolic enzymes in vitro from
      mushroom foot protein.
AB  - This study was to find an effective process to extract bioactive peptides from
      mushroom foot and determine their effects on activation of alcohol metabolic
      enzymes in vitro. The optimum extraction assisted by ultra-high-pressure
      processing of mushroom foot peptides was obtained with a pressure of 400MPa and a
      processing time of 10min. After ultrafiltration, peptides with molecular weight
      of 0-3kDa had the highest activity to activate alcohol dehydrogenase (ADH) and
      aldehyde dehydrogenase (ALDH) by 70.79% and 71.35%, respectively. Following
      dextran gel chromatography, two peaks (p-I and p-II) appeared and the activation
      activities on ADH and ALDH of p-I were 72.00% and 73.43%, both higher than p-II.
      Nine peptides were found in p-I as determined by LC-MS/MS, and two of them (IPLH
      and IPIVLL) were synthesized. IPLH activated ADH and ALDH by 42.7% and 29.2%
      respectively, which were higher than IPIVLL.

PMID- 28450005
TI  - Time-resolved comparative metabolomes for Koji fermentation with brown-, white-,
      and giant embryo-rice.
AB  - A time-resolved non-targeted metabolomic study towards evaluating the effects of
      three rice substrate types viz., white rice (WR), giant embryo rice (GER), and
      brown rice (BR), on Koji fermentation was performed. Notwithstanding the
      relatively higher proportions of metabolites in unfermented BR (BR 0>WR 0, GER
      0), the relative levels of metabolic repertoire in BR Koji were marginally
      enhanced during 36h fermentation except those for phenolic acids, fatty acids,
      and vitamins. The WR Koji showed higher levels of lysophospholipids (LysoPC's)
      and protease-released amino acids (WR 36>GER 36>BR 36). The higher beta
      glucosidase activity in GER Koji effected the increased levels of sugars and
      flavonoid aglycons complementing its higher antioxidant activity (GER Koji>BR
      Koji~WR Koji). The present study holistically underpins the dynamic metabolomes
      and enzymatic states during rice Koji fermentation with varying substrate types.
      The present study finds applications in optimization of commercial Koji
      production.

PMID- 28450006
TI  - Metabolic profiles from two different breakfast meals characterized by 1H NMR
      based metabolomics.
AB  - It is challenging to measure dietary exposure with techniques that are both
      accurate and applicable to free-living individuals. We performed a cross-over
      intervention, with 24 healthy individuals, to capture the acute metabolic
      response of a cereal breakfast (CB) and an egg and ham breakfast (EHB). Fasting
      and postprandial urine samples were analyzed using 1H nuclear magnetic resonance
      (NMR) spectroscopy and multivariate data analysis. Metabolic profiles were
      distinguished in relation to ingestion of either CB or EHB.
      Phosphocreatine/creatine and citrate were identified at higher concentrations
      after consumption of EHB. Beverage consumption (i.e., tea or coffee) could
      clearly be seen in the data. 2-furoylglycine and 5-hydroxymethyl-2-furoic acid -
      potential biomarkers for coffee consumption were identified at higher
      concentrations in coffee drinkers. Thus 1H NMR urine metabolomics is applicable
      in the characterization of acute metabolic fingerprints from meal consumption and
      in the identification of metabolites that may serve as potential biomarkers.

PMID- 28450007
TI  - Human intervention study to investigate the intestinal accessibility and
      bioavailability of anthocyanins from bilberries.
AB  - We investigated the importance of the large intestine on the bioavailability of
      anthocyanins from bilberries in humans with/without a colon. Low bioavailability
      of anthocyanins in plasma and urine was observed in the frame of this study.
      Anthocyanins reached the circulation mainly as glucuronides. Analysis of ileal
      effluents (at end of small intestine) demonstrated that 30% of ingested
      anthocyanins were stable during 8h passage through the upper intestine. Only 20%
      degradants were formed and mostly intact anthocyanins were absorbed from the
      small intestine. Higher amounts of degradants than anthocyanins reached the
      circulation after bilberry extract consumption in both groups of subjects.
      Comparison of the bioavailability of anthocyanins in healthy subjects versus
      ileostomists revealed substantially higher amounts of anthocyanins and degradants
      in the plasma/urine of subjects with an intact gut. The results suggested that
      the colon is a significant site for absorption of bioactive components such as
      anthocyanins and their degradation products.

PMID- 28450008
TI  - Flavanol plasma bioavailability is affected by metabolic syndrome in rats.
AB  - Flavanols, which exert several health benefits, are metabolized after ingestion.
      Factors such as the host physiological condition could affect the metabolism and
      bioavailability of flavanols, influencing their bioactivities. This study aimed
      to qualitatively evaluate whether a pathological state influenced flavanol plasma
      bioavailability. Standard and cafeteria (CAF) diet fed rats, a robust model of
      metabolic syndrome (MeS), were administered 1000mg/kg of flavanol enriched grape
      seed polyphenol extract (GSPE). Flavanols and their metabolites were quantified
      by HPLC-MS/MS in plasma before and at 2, 4, 7, 24, and 48h after GSPE ingestion.
      Results showed that in CAF administered rats the maximum time of plasma flavanol
      concentration was delayed and these animals presented higher levels of plasma
      phase-II metabolites as well as altered microbial metabolites. In conclusion,
      this study demonstrated that MeS pathological state modified flavanol
      bioavailability, supporting the hypothesis that flavanol metabolism, and
      therefore flavanol functionality, depend on the organism's state of health.

PMID- 28450009
TI  - A double-label time-resolved fluorescent strip for rapidly quantitative detection
      of carbofuran residues in agro-products.
AB  - A rapid and quantitative time-resolved fluorescent immunochromatographic assay
      (TRFICA) for detecting carbofuran residues in agro-products was reported in this
      paper. This assay was developed based on double-label immunoprobes, one of which
      was a carbofuran-specific antibody coupled with europium microbeads for the test
      (T) line signal while the other was mouse IgG coupled with europium microbeads
      for the control (C) line signal. Quantitative relationships between carbofuran
      concentrations and T/C ratios were established to determine the analyte
      concentration. To increase assay accuracy, four standard curves were established
      for the agro-products (green bean, cabbage, apple, and pear). The limits of
      detection (LODs) ranged from 0.04 to 0.76mgL-1. The spiked recoveries of
      carbofuran in the agro-products were in the range of 81-103%, which was in good
      agreement with a standard HPLC method. Therefore, we provided a new and reliable
      method for determination of N-methylcarbamate pesticide carbofuran residues in
      agro-products including vegetables and fruits.

PMID- 28450010
TI  - Fatty acid composition and its association with chemical and sensory analysis of
      boar taint.
AB  - A certain level of disagreement between the chemical analysis of androstenone and
      skatole and the human perception of boar taint has been found in many studies.
      Here we analyze whether the fatty acid composition can explain such inconsistency
      between sensory evaluation and chemical analysis of boar taint compounds.
      Therefore, back fat samples (n=143) were selected according to their sensory
      evaluation by a 10-person sensory panel, and the chemical analysis (stable
      isotope dilution analysis with headspace solid-phase microextraction and gas
      chromatography-mass spectrometry) of androstenone and skatole. Subsequently a
      quantification of fatty acids using gas chromatography-flame ionization detection
      was conducted. The correlation analyses revealed that several fatty acids are
      significantly correlated with androstenone, skatole, and the sensory rating.
      However, multivariate analyses (principal component analysis) revealed no
      explanation of the fatty acid composition with respect to the (dis-)agreement
      between sensory and chemical analysis.

PMID- 28450011
TI  - Impact of ingredients on the elemental content of baby foods.
AB  - The levels of the minerals: Ca, K, Mg, Na, P, and the trace elements: Cd, Cu, Fe,
      Mn, Ni, Pb, Se, Zn were determined in foods for 4-6, 7+ and 10+ months old babies
      in a brand available on the UK market. The mineral contents in the vegetarian
      meals for all the age groups were similar, in contrast, when compared to the non
      vegetarian options, the Ca, Na and P levels were higher in the former. Both the
      trace elements and minerals levels in the 4-6months vegetarian meal were the
      lowest of all the products analysed. The Cu, Se and Zn levels in all the meals
      were comparable to those in mature human breast milk. Calculations of the
      following molar ratios: Zn:Cu, Fe:Zn, and Fe:Mn, pairs of elements that have been
      shown to interaction antagonistically, were higher in the vegetarian meals.

PMID- 28450012
TI  - Apocarotenoids determination in Capsicum chinense Jacq. cv. Habanero, by
      supercritical fluid chromatography-triple-quadrupole/mass spectrometry.
AB  - Relatively few studies are available in the literature on the apocarotenoids
      occurrence in food which are based on liquid chromatographic separation
      approaches and no reports are available on the apocarotenoids separation by SFC
      APCI (+/-)/QqQ/MS. The dual purpose of this research was to investigate the
      apocarotenoids presence in red habanero peppers and to develop a novel SFC
      APCI(+/-)/QqQ/MS methodology, using a novel fused-core C30 column, for the
      apocarotenoids detection in a fast and efficient way, for the first time. In this
      study, 25 different apocarotenoids were identified, 14 were free apocarotenoids
      and 11 were apocarotenoids fatty acids esters. The methodology allowed for all
      the separations to occur in less then five minutes. The detected Apo-10'-, Apo
      14'- and Apo-15-capsorubinals and different Apo-8'-capsorubinal and Apo-10'
      zeaxanthinals fatty acid esters had not been previously tentatively identified in
      any Capsicum species and, to the best of our knowledge, in any food matrix.

PMID- 28450013
TI  - Extraction, identification, and antioxidant and anticancer tests of seven
      dihydrochalcones from Malus 'Red Splendor' fruit.
AB  - Five dihydrochalcone compounds, including phlorizin, trilobatin, 3
      hydroxyphlorizin, sieboldin and phloretin 2'-xyloglucoside, were isolated from
      ornamental Malus 'Red Splendor' fruit. The chemical structures of these compounds
      were elucidated by LC-ESI-MS and NMR. Phloretin and 3-hydroxyphloretin were
      produced by hydrolysis. The antioxidant capacities of these seven compounds were
      examined by DPPH and ABTS assays, while their cytotoxicity to five cancer cell
      lines were evaluated by the MTT assay. The results showed that the DPPH assay
      mainly reflected the antioxidant capacity of the B ring, whereas the ABTS assay
      was mostly related to the A ring of the dihydrochalcone molecule. Moreover, 3
      hydroxyphloretin was the best antioxidant among the seven compounds. Both
      glycosylation of the A ring and the ortho phenolic hydroxyl groups of the B ring
      were important for the cytotoxicity of dihydrochalcone molecules. Sieboldin and 3
      hydroxyphlorizin exhibited better cytotoxicity than other dihydrochalcone
      compounds. Dihydrochalcones from Malus may benefit human health.

PMID- 28450014
TI  - Nutritional content and health benefits of sun-dried and salt-aged radish (takuan
      zuke).
AB  - We investigated the nutritional characteristics of salted radish roots (takuan
      zuke) prepared using different methods: takuan-zuke based on sun-drying (hoshi)
      or salt-pressing (shio-oshi) dehydration, different salt-aging temperatures, and
      salting with rice bran. We examined differences in nutritional substances in
      salted radish using chromatographic analysis, bioassay methods, and multivariate
      analysis. We previously reported that the amount of gamma-aminobutyrate in takuan
      zuke was increased by both dehydration treatments. In the present study, we
      observed that sucrose and proline were increased by sun-drying treatment, while
      little change occurred with salt-pressing treatment. Branched-chain amino acids
      were increased by both treatments. Interestingly, free fatty acids increased with
      salt-aging duration, irrespective of the dehydration method. Addition of rice
      bran to long salt-aging treatment increased the levels of niacin, glutamate, and
      acetate. Metabolite concentrations were higher in hoshi takuan-zuke than shio
      oshi takuan-zuke. Our comprehensive analysis reveals effects of specific
      manufacturing conditions on beneficial components of takuan-zuke.

PMID- 28450015
TI  - A comparative study of anthocyanin distribution in purple and blue corn
      coproducts from three conventional fractionation processes.
AB  - The aim was to compare the distribution of ANCs in purple and blue corn
      coproducts from three conventional corn fractionation processes and linking ANC
      partitioning in different coproducts to corn kernel phenotype. Total monomeric
      anthocyanin (TA) from purple corn extract was 4933.1+/-43.4mg cyanidin-3
      glucoside equivalent per kg dry corn, 10 times more than blue corn. In dry milled
      purple corn, maximum ANCs were present in the pericarp (45.9% of total ANCs) and
      in wet-milling they were concentrated in steeping water (79.1% of total ANCs).
      For blue corn, the highest TA was in small grits and gluten slurry in dry-milling
      and wet-milling coproducts, respectively. HPLC showed the highest concentration
      of each ANC in steeping water for purple corn coproducts. Micrographs of kernel
      showed pigments concentrated in pericarp layer of purple but only in aleurone of
      blue corn. ANCs can concentrate in certain coproducts depending upon physical
      distribution of pigments in kernel.

PMID- 28450016
TI  - Peptide selection and antibody generation for the prospective immunorecognition
      of Cry1Ab16 protein of transgenic maize.
AB  - The introduction of genes isolated from different Bacillus thuringiensis strains
      to express Cry-type toxins in transgenic crops is a common strategy to confer
      insect resistance traits. This work intended to extensively in silico analyse
      Cry1A(b)16 protein for the identification of peptide markers for the
      biorecognition of transgenic crops. By combining two different strategies based
      on several bioinformatic tools for linear epitope prediction, a set of seven
      peptides was successfully selected as potential Cry1A(b)16 immunogens. For the
      prediction of conformational epitopes, Cry1A(b)16 models were built on the basis
      of three independent templates of homologue proteins of Cry1A(a) and Cry1A(c)
      using an integrated approach. PcH_736-746 and PcH_876-886 peptides were selected
      as the best candidates, being synthesised and used for the production of
      polyclonal antibodies. To the best of our knowledge, this is the first attempt of
      selecting and defining linear peptides as immunogenic markers of Cry1A(b)-type
      toxins in transgenic maize.

PMID- 28450017
TI  - Microwave-assisted extraction of silkworm pupal oil and evaluation of its fatty
      acid composition, physicochemical properties and antioxidant activities.
AB  - Microwave-assisted extraction (MAE) of oil from silkworm pupae was firstly
      performed in the present research. The response surface methodology was applied
      to optimize the parameters for MAE. The yield of oil by MAE was 30.16% under
      optimal conditions of a mixed solvent consisting of ethanol and n-hexane (1:1,
      v/v), microwave power (360W), liquid to solid ratio (7.5/1mL/g), microwave time
      (29min). Moreover, oil extracted by MAE was quantitatively (yield) and
      qualitatively (fatty acid profile) similar to those obtained using Soxhlet
      extraction (SE), but oil extracted by MAE exhibited favourable physicochemical
      properties and oxidation stability. Additionally, oil extracted by MAE had a
      higher content of total phenolic, and it showed stronger antioxidant activities.
      Scanning electron microscopy revealed that microwave technique efficiently
      promoted the release of oil by breaking down the cell structure of silkworm
      pupae. Therefore, MAE can be an effective method for the silkworm pupal oil
      extraction.

PMID- 28450018
TI  - Interaction between natural antioxidants derived from cinnamon and cocoa in
      binary and complex mixtures.
AB  - Cinnamon and cocoa are known to be valuable sources of bioactive phytochemicals,
      mainly the polyphenols. This paper investigates the potential antioxidant
      activity of cinnamon and cocoa extract and the interaction of their mixtures by
      various in vitro tests. Moreover, the combination effect of their constituents in
      a binary mixture was studied. Two representative active compounds of chocolate
      (epicatechin, catechin) were combined with seven of cinnamon (gallic acid, tannic
      acid, quercetin, sinapic acid, cinnamic acid, eugenol and cinnamaldehyde) in
      multilevel ratios. The results indicate that the addition of the cinnamon extract
      significantly increased the antioxidant activity of the cocoa extract. The
      interaction ranged from synergetic to antagonistic. The interaction was less
      synergetic when cinnamon extract was added in higher proportion. The interaction
      of their constituents substantially influenced the antioxidant activity of the
      mixture and was dependent on the ratio. The kinetics' study could elucidate how
      the polyphenols work in a mixture.

PMID- 28450019
TI  - Simultaneous determination of organophosphorus pesticides in fruits and
      vegetables using atmospheric pressure gas chromatography quadrupole-time-of
      flight mass spectrometry.
AB  - This paper describes the application of atmospheric pressure gas chromatography
      quadrupole-time-of-flight mass spectrometry for the simultaneous determination of
      organophosphorus pesticides in apple, pear, tomato, cucumber and cabbage. Soft
      ionization with atmospheric pressure ionization source was compared with
      traditional electron impact ionization (EI). The sensitivity of GC coupled to
      atmospheric pressure ionization (APGC) for all the analytes was enhanced by 1.0
      8.2 times. The ionization modes with atmospheric pressure ionization source was
      studied by comparing the charge-transfer and proton-transfer conditions. The
      optimized QuEChERs method was used to pretreat the samples. The calibration
      curves were found linear from 10 to 1000MUg/L, obtaining correlation coefficients
      higher than 0.9845. Satisfactory mean recovery values, in the range of 70.0
      115.9%, and satisfactory precision, with all RSDr <19.7% and all RSDR values
      <19.5% at the three fortified concentration levels for all the fifteen OPPs. The
      results demonstrate the potential of APGC-QTOF-MS for routine quantitative
      analysis of organophosphorus pesticide in fruits and vegetables.

PMID- 28450020
TI  - Metabolic profiling approach to determine phenolic compounds of virgin olive oil
      by direct injection and liquid chromatography coupled to mass spectrometry.
AB  - A LC-MS method involving direct injection of extra-virgin olive oil (EVOO) -
      after a simple dilution - for determining its phenolic compounds has been
      developed. Optimization of the most appropriate solvent for sample dilution,
      selection of the optimum oil/solvent ratio, and establishment of column cleaning
      strategy and maximum number of injections were some of the most relevant steps.
      Then, the analytical parameters of the method were evaluated, establishing LOD
      (from 3.3 to 31.6ug/L) and LOQ, precision (RSD values for inter-day repeatability
      were found between 3.49 and 6.12%), and trueness (within the range 89.9-102.3%
      for 1.0mg/L) and checking possible matrix effect (which was no significant).
      Three kinds of calibration were used: external standard, standard addition and
      calibration in a phenols-free matrix, which was subsequently applied to quantify
      the phenolic compounds in 16 EVOOs (from 6 cultivars). A total of 21 compounds
      were determined without the need of using any extraction protocol.

PMID- 28450021
TI  - Volatile composition and sensory characteristics of onion powders prepared by
      convective drying.
AB  - Volatile composition and sensory characteristics of onion powders prepared by
      convective drying at different temperatures (50, 70, and 90 degrees C) were
      investigated. Dipropyl disulfide was the major volatile compound in fresh onion
      (77.70% of total volatile compounds). However it was considerably lost during
      drying, reaching 6.93-32.25ug/g solids. Dipropyl disulfide showed a positive
      correlation with green sensory attribute perceived by descriptive sensory
      analysis. Thiophenes, which were responsible for caramel and sweet attributes,
      were produced by drying especially when the drying temperature was high.
      Aldehydes, another type of volatile compound found in fresh onion, showed a
      positive correlation with humidity. The aldehyde content in dried onion was the
      highest at the lowest drying temperature, possibly because the aldehydes were
      produced by the residual enzymes in fresh onion. Using a low temperature for
      drying was ideal to retain the aroma of fresh onion.

PMID- 28450022
TI  - Physicochemical properties and cellular protection against oxidation of degraded
      Konjac glucomannan prepared by gamma-irradiation.
AB  - Konjac glucomannan (KGM) is an important functional polysaccharide in food
      research. However, unstable dispersibility of KGM inhibits its in-depth study and
      wide application. In this study, a degraded KGM (100kGy-KGM), which showed
      excellent dispersibility and specific physicochemical properties, were obtained
      by gamma-irradiation in a dosage of 100kGy. We investigated the protective effect
      of 100kGy-KGM against H2O2 induced oxidative damage in LO2 cells. Our results
      demonstrated that pretreatment of LO2 cells with 100kGy-KGM not only
      significantly increased cellular survivals and activities of GSH-Px and CAT, but
      also reduced levels of LDH, MDA and intracellular accumulation of ROS. The marked
      protective effect against oxidative damage and excellent dispersibility in 100kGy
      KGM allowed its possible use as an antioxidant. Our study provided fundamental
      knowledge to understand the structure-functions relationships of degraded-KGM,
      which could result in a theoretical guidance for the future application of KGM.

PMID- 28450023
TI  - Aggregation of gluten proteins in model dough after fibre polysaccharide
      addition.
AB  - FT-Raman spectroscopy, thermogravimetry and differential scanning calorimetry
      were used to study changes in structure of gluten proteins and their thermal
      properties influenced by four dietary fibre polysaccharides (microcrystalline
      cellulose, inulin, apple pectin and citrus pectin) during development of a model
      dough. The flour reconstituted from wheat starch and wheat gluten was mixed with
      the polysaccharides in five concentrations: 3%, 6%, 9%, 12% and 18%. The obtained
      results showed that all polysaccharides induced similar changes in secondary
      structure of gluten proteins concerning formation of aggregates (1604cm-1), H
      bonded parallel- and antiparallel-beta-sheets (1690cm-1) and H-bonded beta-turns
      (1664cm-1). These changes concerned mainly glutenins since beta-structures are
      characteristic for them. The observed structural changes confirmed hypothesis
      about partial dehydration of gluten network after polysaccharides addition. The
      gluten aggregation and dehydration processes were also reflected in the DSC
      results, while the TGA ones showed that gluten network remained thermally stable
      after polysaccharides addition.

PMID- 28450024
TI  - Extension of raw watermelon juice shelf-life up to 58days by hyperbaric storage.
AB  - Hyperbaric storage (HS) of raw watermelon juice, at 50, 62.5 and 75MPa, at
      temperatures of 10, 15 and ~25 degrees C (room temperature, RT), was studied to
      evaluate shelf-life comparatively to refrigeration (RF, 4 degrees C). Generally,
      RF caused an increase of microbial loads to values >=6.0logCFU/mL after 7days of
      storage. Contrarily, HS at 62.5/75MPa (15 degrees C) showed a reduction of
      initial loads, by at least 2.5logCFU/mL, up to 58days, while pH and colour values
      did not changed under these HS conditions. Additionally, the combination of a
      lower temperature with HS has beneficial effects to control microbial
      development, particularly for the lower pressure studied (50MPa/10 degrees C). In
      conclusion, HS increased watermelon juice shelf-life for at least 58days,
      indicating a great potential for future RF replacement.

PMID- 28450025
TI  - Effects of surfactants on the formation of gelatin nanofibres for controlled
      release of curcumin.
AB  - This work studied the effects of non-ionic Tween 80, anionic sodium dodecyl
      sulfonate (SDS) and cationic cetyltrimethyl ammonium bromide (CTAB) surfactants
      on the morphology of electrospun gelatin nanofibres, and on the release
      behaviour, antioxidant activity and antimicrobial activity of encapsulated
      curcumin. Scanning electron micrographs showed that addition of SDS significantly
      increased the nanofibre diameter. Fourier transform infrared and differential
      scanning calorimetry analysis indicated that gelatin and SDS intimately
      interacted via electrostatic and hydrophobic interactions. However, these
      interactions inhibited the release of curcumin from the nanofibres with SDS,
      while CTAB and Tween 80 both facilitated the release. SDS and Tween 80 showed
      protective effects on curcumin from the attack of 2,2-diphenyl-1-picryl-hydrazyl
      hydrate (DPPH) radicals, and the increased release of curcumin from nanofibres
      with CTAB or Tween 80 resulted in a higher reducing power. The antimicrobial
      activity results suggested that the curcumin encapsulated gelatin nanofibres with
      CTAB exhibited effective inhibition against Staphylococcus aureus.

PMID- 28450026
TI  - Formation of (E)-nerolidol in tea (Camellia sinensis) leaves exposed to multiple
      stresses during tea manufacturing.
AB  - (E)-Nerolidol is a volatile sesquiterpene that contributes to the floral aroma of
      teas (Camellia sinensis). The unique manufacturing process for oolong tea
      involves multiple stresses, resulting in a high content of (E)-nerolidol, which
      is not known to form in tea leaves. This study aimed to determine the formation
      mechanism of (E)-nerolidol in tea exposed to multiple stresses during tea
      manufacture. C. sinensis (E)-nerolidol synthase (CsNES) recombinant protein,
      found in the cytosol, was found to transform farnesyl diphosphate into (E)
      nerolidol. CsNES was highly expressed during the oolong tea turn over process,
      resulting in (E)-nerolidol accumulation. Continuous mechanical damage, simulating
      the turn over process, significantly enhanced CsNES expression level and (E)
      nerolidol content. The combination of low temperature stress and mechanical
      damage had a synergistic effect on (E)-nerolidol formation. This is the first
      evidence of (E)-nerolidol formation mechanism in tea leaves and a characteristic
      example of plant volatile formation in response to dual stresses.

PMID- 28450027
TI  - Structuring colloidal oat and faba bean protein particles via enzymatic
      modification.
AB  - Oat and faba bean protein isolates were treated with transglutaminase from
      Streptomyces mobaraensis and tyrosinase from Trichoderma reesei to modify the
      colloidal properties of protein particles in order to improve their colloidal
      stability and foaming properties. Transglutaminase crosslinked faba bean protein
      extensively already with 10nkat/g enzyme dosage. Oat protein was crosslinked to
      some extent with transglutaminase with higher dosages (100 and 1000nkat/g).
      Transglutaminase increased the absolute zeta-potential values and reduced the
      particle size of oat protein particles. As a result, the colloidal stability and
      foaming properties were improved. Tyrosinase had limited crosslinking ability on
      both plant protein materials. Tyrosinase greatly reduced the solubility of oat
      protein despite limited crosslinking. Tyrosinase did not have effect on zeta
      potential or colloidal stability of either protein, but it impaired foaming
      properties of both. Thus, the crosslinking enzymes studied caused significantly
      different end product functionality, presumably due to the different mechanism of
      action.

PMID- 28450028
TI  - Effects of high pressure processing on activity and structure of soluble acid
      invertase in mango pulp, crude extract, purified form and model systems.
AB  - The effects of high pressure processing (HPP) on the activity of soluble acid
      invertase (SAI) in mango pulp, crude extract, purified SAI and purified SAI in
      model systems (pectin, bovine serum albumin (BSA), sugars and pH 3-7) were
      investigated. The activity of SAI in mango pulp was increased after HPP, and that
      in crude extract stayed unchanged. The activity of purified SAI was decreased
      after HPP at 45 and 50 degrees C. Pectin exhibited a concentration-dependent
      protection for purified SAI against HPP at 50 degrees C/600MPa for 30min. Pectin
      that had an esterification degree (DE) of 85% exhibited a greater protection than
      pectin that had a DE of 20-34%. BSA, acidic pH (3-6) and sucrose also exhibited
      protection for purified SAI against HPP. HPP at 50 degrees C/600MPa for 30min
      disrupted the secondary structure and tertiary structure of purified SAI, but no
      aggregation of purified SAI was observed after HPP.

PMID- 28450029
TI  - Call for improved military policy to support breastfeeding among U.S. armed
      forces.

PMID- 28450030
TI  - Diversity: A key aspect of 21st century faculty roles as implemented in the
      Robert Wood Johnson Foundation Nurse Faculty Scholars program.
AB  - BACKGROUND: Academic nursing faculty play a vital role in recruiting a diverse
      student body to increase the diversity of the profession and educate students to
      provide culturally sensitive care to expand equitable health care. PURPOSE: The
      purpose of the study is to present the Robert Wood Johnson Foundation Nurse
      Faculty Scholars program diversity initiatives and outcomes. METHODS: Data on the
      diversity of the 90 scholars and their diversity-related leadership positions
      were compiled. DISCUSSION: Although the program was designed with selection
      criteria to encourage racial/ethnic and gender diversity, it was not until a
      diversity strategic plan was designed and implemented that sufficient diversity
      in the applicant pool and consistent diversity among the scholars was achieved.
      The program also included highly evaluated leadership content in diversity and
      inclusion. CONCLUSIONS: Lessons learned from the program are important for the
      assurance of continued diversity among tenure-track nursing faculty, commitment
      to diversity in the nursing workforce among all faculty, and support in nursing
      education on providing culturally sensitive nursing care and nursing research
      that addresses health inequities.

PMID- 28450032
TI  - Broadband Acoustic Measurement of an Agar-Based Tissue-Mimicking-Material: A
      Longitudinal Study.
AB  - Commercially available ultrasound quality assurance test phantoms rely on the
      long-term acoustic stability of the tissue-mimicking-material (TMM). Measurement
      of the acoustic properties of the TMM can be technically challenging, and it is
      important to ensure its stability. The standard technique is to film-wrap samples
      of TMM and to measure the acoustic properties in a water bath. In this study, a
      modified technique was proposed whereby the samples of TMM are measured in a
      preserving fluid that is intended to maintain their characteristics. The acoustic
      properties were evaluated using a broadband pulse-echo substitution technique
      over the frequency range 4.5-50 MHz at 0, 6 and 12 months using both techniques.
      For both techniques, the measured mean values for the speed of sound and
      attenuation were very similar and within the International Electrotechnical
      Commission-recommended value. However, the results obtained using the proposed
      modified technique exhibited greater stability over the 1-y period compared with
      the results acquired using the standard technique.

PMID- 28450031
TI  - Racial and Ethnic Disparities in Early-Stage Lung Cancer Survival.
AB  - BACKGROUND: Black patients with lung cancer diagnosed at early stages-for which
      surgical resection offers a potential cure-experience worse overall survival than
      do their white counterparts. We undertook a population-based study to estimate
      the racial and ethnic disparity in death from competing causes and assessed its
      contribution to the gap in overall survival among patients with early-stage lung
      cancer. METHODS: We collected survival time data for 105,121 Hispanic, non
      Hispanic Asian, non-Hispanic black, and non-Hispanic white patients with early
      stage (IA, IB, IIA, and IIB) lung cancer diagnosed between 2004 and 2013 from the
      Surveillance, Epidemiology, and End-Results registries. We modeled survival time
      using competing risk regression and included as covariates sex, age at diagnosis,
      race/ethnicity, stage at diagnosis, histologic type, type of surgical resection,
      and radiation sequence. RESULTS: Adjusting for demographic, clinical, and
      treatment characteristics, non-Hispanic blacks experienced worse overall survival
      compared with non-Hispanic whites (adjusted hazard ratio [aHR], 1.05; 95% CI,
      1.02-1.08), whereas Hispanics and non-Hispanic Asians experienced better overall
      survival (aHR, 0.93; 95% CI, 0.89-0.98; and aHR, 0.82; 95% CI, 0.79-0.86,
      respectively). Worse survival from competing causes of death, such as
      cardiovascular disease and other cancers-rather than from lung cancer itself-led
      to the disparity in overall survival among non-Hispanic blacks (adjusted relative
      risk, 1.07; 95% CI, 1.02-1.12). CONCLUSIONS: Narrowing racial and ethnic
      disparities in survival among patients with early-stage lung cancer will rely on
      more than just equalizing access to surgical resection and will need to include
      better management and treatment of smoking-related comorbidities and diseases.

PMID- 28450033
TI  - Plaque Topographic Characterization: A New Element to Investigate Carotid
      Atherosclerosis.

PMID- 28450034
TI  - Microbubble Enzyme-Linked Immunosorbent Assay for the Detection of Targeted
      Microbubbles in in Vitro Static Binding Assays.
AB  - Targeted microbubbles (MBs) are ultrasound contrast agents that are
      functionalized with a ligand for ultrasound molecular imaging of endothelial
      markers. Novel targeted MBs are characterized in vitro by incubation in protein
      coated wells, followed by binding quantification by microscopy or ultrasound
      imaging. Both methods provide operator-dependent results: Between 3 and 20 fields
      of view from a heterogeneous sample are typically selected for analysis by
      microscopy, and in ultrasound imaging, different acoustic settings affect signal
      intensities. This study proposes a new method to reproducibly quantify MB binding
      based on enzyme-linked immunosorbent assay (ELISA), in which bound MBs are
      revealed with an enzyme-linked antibody. MB-ELISA was adapted to in vitro static
      binding assays, incubating the MBs in inverted position or by agitation, and
      compared with microscopy. The specificity and sensitivity of MB-ELISA enable the
      reliable quantification of MB binding in a rapid, high-throughput and whole-well
      analysis, facilitating the characterization of new targeted contrast agents.

PMID- 28450035
TI  - Evaluation of Optic Nerve with Strain and Shear Wave Elastography in Patients
      with Behcet's Disease and Healthy Subjects.
AB  - The objective of this study was to investigate the elasticity characteristics of
      the optic nerve using strain and shear wave elastography in patients with
      Behcet's disease and to compare the results with those of healthy volunteers.
      Forty-six optic nerves from patients with Behcet's disease and 54 optic nerves
      from healthy volunteers were investigated prospectively in this study using
      strain and shear wave elastography. There was a statistically significant
      difference in terms of elasticity patterns between patients and healthy
      volunteers (p < 0.001). Elastographic images of healthy volunteers revealed most
      optic nerves to be type 3 (51.8%); however, type 2 (40.7%) and type 1 (7.5%) were
      also observed. Elastographic examination of Behcet's disease patients revealed
      type 2 in 52.2%, type 1 in 43.5% and type 3 in 4.3% of patients. Statistically
      significant differences were observed between patients and healthy volunteers in
      the analysis of shear wave elastography values (p < 0.001). Receiver operating
      characteristic curve analysis was perfect (0.933) (95% CI = 0.885-0.980), and a
      cutoff value of 16.5 kPa shear had very high sensitivity and specificity for the
      patient group. Strain and shear wave elastography findings for the optic nerves
      of patients with Behcet's disease were significantly different from those for
      healthy volunteers.

PMID- 28450036
TI  - Dynamic Enhancement of B-Mode Cardiac Ultrasound Image Sequences.
AB  - Limited contrast, along with speckle and acoustic noise, can reduce the
      diagnostic value of echocardiographic images. This study introduces dynamic
      histogram-based intensity mapping (DHBIM), a novel approach employing temporal
      variations in the cumulative histograms of cardiac ultrasound images to contrast
      enhance the imaged structures. DHBIM is then combined with spatial compounding to
      compensate for noise and speckle. The proposed techniques are quantitatively
      assessed (32 clinical data sets) employing (i) standard image quality measures
      and (ii) the repeatability of routine clinical measurements, such as chamber
      diameter and wall thickness. DHBIM introduces a mean increase of 120.9% in
      tissue/chamber detectability, improving the overall repeatability of clinical
      measurements by 17%. The integrated approach of DHBIM followed by spatial
      compounding provides the best overall enhancement of image quality and diagnostic
      value, consistently outperforming the individual approaches and achieving a
      401.4% average increase in tissue/chamber detectability with an associated 24.3%
      improvement in the overall repeatability of clinical measurements.

PMID- 28450037
TI  - Prognostic Impact of Age and Hemoglobin in Acute ST-Segment Elevation Myocardial
      Infarction Treated With Reperfusion Therapy.
AB  - Advanced age and low hemoglobin levels have been associated with a poor prognosis
      in ST-segment elevation myocardial infarction (STEMI). We studied 1,111 patients
      with STEMI who received reperfusion treatment (1,032 [92.9%] primary angioplasty
      and 79 [7.1%] fibrinolysis without rescue percutaneous coronary intervention).
      Mean age was 64.1 +/- 14.0 years, and 23.2% were women. Patients in the last age
      quartile (>76 years) were more frequently women, presented more risk factors
      (except smoking), received thrombolysis less frequently, had less complete
      revascularization, and presented more complications and higher mortality.
      Hemoglobin level at admission was associated with age and ranged from 14.8 +/-
      1.5 g/dl in the first quartile to 13.2 +/- 1.8 g/dl in the last, p <0.001.
      Multivariate analysis identified age as a predictor of in-hospital and long-term
      mortality (odds ratio 1.04, 95% confidence interval [CI] 1.00 to 1.07, hazard
      ratio 1.06, 95% CI 1.04 to 1.08). Hemoglobin levels were associated with better
      survival (odds ratio 0.8, 95% CI 0.6 to 0.9, hazard ratio 0.85, 95% CI 0.78 to
      0.92). The other predictors of inhospital mortality were Killip class, chronic
      kidney disease, left ventricular ejection fraction, significant pericardial
      effusion, and ventricular arrhythmias. The association of hemoglobin with
      hospital mortality was seen in men and in women >=65 years. In men >=65 years,
      this association was also present in those with hemoglobin levels in the normal
      range. In conclusion, in patients with STEMI, hemoglobin is an independent
      predictor of inhospital and long-term mortality, especially in those aged >=65
      years. This association is also present in men >=65 years with normal hemoglobin
      levels.

PMID- 28450038
TI  - Major Electrocardiographic Abnormalities According to the Minnesota Coding System
      Among Brazilian Adults (from the ELSA-Brasil Cohort Study).
AB  - The electrocardiogram is a simple and useful clinical tool; nevertheless, few
      studies have evaluated the prevalence of electrocardiographic abnormalities in
      the Latin American population. This study aims to evaluate the major
      electrocardiographic abnormalities according to the Minnesota coding system in
      Brazilian adults, stratified by gender, age, race, and cardiovascular risk
      factors. Data from 14,424 adults (45.8% men, age 35 to 74 years) were obtained at
      baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil),
      according to standardized protocol. The electrocardiogram were obtained with the
      Burdick Atria 6100 machine, stored on Pyramis System, automatically coded
      according to the Minnesota coding system by the Glasgow University software and
      then manually revised. Major abnormalities were more prevalent in men than women
      (11.3% and 7.9%, p <0.001). These differences were consistent through the
      different age groups, race, and number of cardiovascular risk factors.
      Electrocardiographic major abnormalities were more prevalent in black
      participants for both men (black: 15.1%, mixed: 10.4%, white: 11.1%, p = 0.001)
      and women (black: 10%, mixed: 7.6%, white: 7.2%, p = 0.004). In conclusion, in
      this large sample of Brazilian adults, the prevalence of major
      electrocardiographic abnormalities was higher among men, the elderly, black, and
      among people with more cardiovascular risk factors.

PMID- 28450039
TI  - Characterization of Chronic Aortic and Mitral Regurgitation Undergoing Valve
      Surgery Using Cardiovascular Magnetic Resonance.
AB  - Grading of chronic aortic regurgitation (AR) and mitral regurgitation (MR) by
      cardiovascular magnetic resonance (CMR) is currently based on thresholds, which
      are neither modality nor quantification method specific. Accordingly, this study
      sought to identify CMR-specific and quantification method-specific thresholds for
      regurgitant volumes (RVols), RVol indexes, and regurgitant fractions (RFs), which
      denote severe chronic AR or MR with an indication for surgery. The study
      comprised patients with moderate and severe chronic AR (n = 38) and MR (n = 40).
      Echocardiography and CMR was performed at baseline and in all operated AR/MR
      patients (n = 23/25) 10 +/- 1 months after surgery. CMR quantification of AR:
      direct (aortic flow) and indirect method (left ventricular stroke volume [LVSV] -
      pulmonary stroke volume [PuSV]); MR: 2 indirect methods (LVSV - aortic forward
      flow [AoFF]; mitral inflow [MiIF] - AoFF). All operated patients had severe
      regurgitation and benefited from surgery, indicated by a significant postsurgical
      reduction in end-diastolic volume index and improvement or relief of symptoms.
      The discriminatory ability between moderate and severe AR was strong for RVol >40
      ml, RVol index >20 ml/m2, and RF >30% (direct method) and RVol >62 ml, RVol index
      >31 ml/m2, and RF >36% (LVSV-PuSV) with a negative likelihood ratio <= 0.2. In
      MR, the discriminatory ability was very strong for RVol >64 ml, RVol index >32
      ml/m2, and RF >41% (LVSV-AoFF) and RVol >40 ml, RVol index >20 ml/m2, and RF >30%
      (MiIF-AoFF) with a negative likelihood ratio < 0.1. In conclusion, CMR grading of
      chronic AR and MR should be based on modality-specific and quantification method
      specific thresholds, as they differ largely from recognized guideline criteria,
      to assure appropriate clinical decision-making and timing of surgery.

PMID- 28450040
TI  - Comparison of Predictors of Heart Failure With Preserved Versus Reduced Ejection
      Fraction in a Multiracial Cohort of Preclinical Left Ventricular Diastolic
      Dysfunction.
AB  - Preclinical diastolic dysfunction (PDD) is a well-known but poorly understood
      risk factor for heart failure. We aimed to investigate risk factors contributing
      to progression of PDD to heart failure with preserved ejection fraction (HFpEF)
      and heart failure with reduced ejection fraction (HFrEF). Patients with
      echocardiogram from 2003 to 2008 with left ventricular ejection fraction >=50%,
      grade I diastolic dysfunction, and free of clinical heart failure were included.
      The end point was incident HFpEF or HFrEF. Cumulative probabilities were
      estimated and multivariable adjusted Cox proportional hazards regressions were
      performed to examine predictors of incident HFpEF and HFrEF. In total, 7,878
      patients with PDD (79.2% nonwhite) were included. At the end of follow-up (median
      5.9 years), 146 patients developed HFrEF, and 635 patients developed HFpEF. The
      10-year cumulative probabilities of HFrEF and HFpEF were 3.1% and 12.6%,
      respectively. Incidence of HFrEF was significantly lower in non-Hispanic blacks
      (2.2%) compared with non-Hispanic whites (4.5%). Age, diabetes, myocardial
      infarction, and renal disease were independent predictors of both HFrEF and
      HFpEF. Male gender, cerebrovascular accident, and low baseline left ventricular
      ejection fraction were associated with HFrEF only; whereas pulmonary disease,
      blood urea nitrogen, and anemia were predictors of HFpEF only. In conclusion, our
      results revealed a distinct set of predictors of HFrEF and HFpEF in patients with
      PDD and underscored a differential approach of risk stratification, prevention,
      and early treatment based on heart failure subtypes.

PMID- 28450041
TI  - Investigating the potential of Oxymatrine as a psoriasis therapy.
AB  - Psoriasis vulgaris is a chronic inflammatory skin disease, stubbornly
      intractable, with substantial consequences for patient physical and mental
      welfare. Approaches currently available to treat psoriasis are not satisfactory
      due to undesirable side-effects or expense. Psoriasis is characterized by
      hyperproliferation and inflammation. Oxymatrine, an active component extracted
      from Sophora flavescens, has been demonstrated to possess anti-proliferation,
      anti-inflammatory, anti-tumorigenic, immune regulation and pro-apoptotic
      properties. This investigation presents a detailed retrospective review examining
      the effect of Oxymatrine on psoriasis and investigates the mechanisms underlying
      patient responses to Oxymatrine. We confirm that Oxymatrine administration
      significantly reduced the Psoriasis Area Severity Index score, with high efficacy
      compared to the control group. In addition, we have found that Oxymatrine
      significantly inhibits the viability, proliferation and differentiation of human
      keratinocyte in vitro. Immunohistochemical analysis indicates Oxymatrine
      significantly suppresses the expression of Pan-Cytokeratin, p63 and keratin 10.
      The results indicate that the suppression of p63 expression may lead to the anti
      proliferation effect of Oxymatrine on human skin keratinocytes. Oxymatrine does
      not affect the formation of basement membrane, which is very important to
      maintain the normal function of human skin keratinocytes. In summary, Oxymatrine
      offers an effective, economical, and safe treatment for patients presenting with
      intractable psoriasis vulgaris.

PMID- 28450042
TI  - Transdiagnostic models of anxiety disorder: Theoretical and empirical
      underpinnings.
AB  - Despite the increasing development, evaluation, and adoption of transdiagnostic
      cognitive behavioral therapies, relatively little has been written to detail the
      conceptual and empirical psychopathology framework underlying transdiagnostic
      models of anxiety and related disorders. In this review, the diagnostic, genetic,
      neurobiological, developmental, behavioral, cognitive, and interventional data
      underlying the model are described, with an emphasis on highlighting elements
      that both support and contradict transdiagnostic conceptualizations. Finally, a
      transdiagnostic model of anxiety disorder is presented and key areas of future
      evaluation and refinement are discussed.

PMID- 28450043
TI  - Anterior Chamber Angle and Anterior Segment Structure of Eyes in Children With
      Early Stages of Retinopathy of Prematurity.
AB  - PURPOSE: To compare structural differences in the anterior chamber angle (ACA)
      and related optic components in children with or without retinopathy of
      prematurity (ROP). DESIGN: Prospective cross-sectional study. METHODS: Setting: A
      referred medical center in Taiwan. STUDY POPULATION: The patients included
      preterm children with a history of ROP who had undergone laser therapy. The
      controls included age-matched healthy full-term children. OBSERVATION PROCEDURE:
      The ACA structures were evaluated using gonioscopy. MAIN OUTCOME MEASURES: The
      angularity of the anterior chamber and associated anatomic changes. RESULTS: We
      examined 54 eyes of 29 preterm children with ROP and 134 eyes of 67 children born
      at term. The eyes of the ROP children exhibited a narrower ACA, steeper iris
      curvature, and more anteriorly inserted iris than those of the full-term children
      (P < .001, P = .002, and P = .08, respectively). The eyes of the ROP children
      also exhibited steeper corneas, shallower anterior chamber depths, thicker
      lenses, and higher degrees of refractive errors (all P < .001) than those of the
      full-term children. The axial lengths did not differ between the 2 groups (P =
      .15). CONCLUSIONS: The eyes of the ROP children presented a narrower ACA and a
      more anteriorly curved and inserted iris than those of the full-term children. A
      steeper cornea, shallower anterior chamber, and greater lens thickness were the
      main structural changes in the anterior segment components of these patients.
      Further research is needed to investigate the association between these
      structural changes and the development of certain ocular diseases, such as
      glaucoma, in these patients.

PMID- 28450044
TI  - Benzyl alcohol induces a reversible fragmentation of the Golgi apparatus and
      inhibits membrane trafficking between endosomes and the trans-Golgi network.
AB  - Benzyl alcohol (BnOH) is widely used as a component of foods, cosmetics,
      household products and medical products. It is generally considered to be safe
      for human use, however, it has been connected to a number of adverse effects,
      including hypersensitivity reactions and neonatal deaths. BnOH is a membrane
      fluidizing agent that can affect membrane protein activity and cellular processes
      such as ligand binding to cell surface receptors, endocytosis and degradation of
      lysosomal cargo. In this study, we examined the effects of BnOH on intracellular
      transport using Shiga toxin (Stx), diphtheria toxin (DT) and ricin. BnOH caused
      reduced toxicity of all three toxins at BnOH concentrations that cause membrane
      fluidization. The reduced toxicity of Stx and ricin was mainly due to inhibition
      of retrograde transport between endosomes and the trans-Golgi network as BnOH had
      small effects on cell association and endocytosis of ricin and Stx. Strikingly,
      BnOH also induced a reversible fragmentation of the Golgi apparatus.

PMID- 28450045
TI  - Arginine-lysine positional swap of the LL-37 peptides reveals evolutional
      advantages of the native sequence and leads to bacterial probes.
AB  - Antimicrobial peptides are essential components of the innate immune system of
      multicellular organisms. Although cationic and hydrophobic amino acids are known
      determinants of these amphipathic molecules for bacterial killing, it is not
      clear how lysine-arginine (K-R) positional swaps influence peptide structure and
      activity. This study addresses this question by investigating two groups of
      peptides (GF-17 and 17BIPHE2) derived from human cathelicidin LL-37. K-R
      positional swap showed little effect on minimal inhibitory concentrations of the
      peptides. However, there are clear differences in bacterial killing kinetics. The
      membrane permeation patterns vary with peptide and bacterial types, but not
      changes in fluorescent dyes, salts or pH. In general, the original peptide is
      more efficient in bacterial killing, but less toxic to human cells, than the K-R
      swapped peptides, revealing the evolutionary significance of the native sequence
      for host defense. The characteristic membrane permeation patterns for different
      bacteria suggest a possible application of these K-R positional-swapped peptides
      as molecular probes for the type of bacteria. Such differences are related to
      bacterial membrane compositions: minimal for Gram-positive Staphylococcus aureus
      with essentially all anionic lipids (cardiolipin and phosphatidylglycerol), but
      evident for Gram-negative Klebsiella pneumoniae, Pseudomonas aeruginosa and
      Escherichia coli with a mixture of phosphatidylethanolamine and
      phosphatidylglycerol. Biophysical characterization found similar structures and
      binding affinities for these peptides in vesicle systems mimicking E. coli and S.
      aureus. It seems that interfacial arginines of GF-17 are preferred over lysines
      in bacterial membrane permeation. Our study sheds new light on the design of
      cationic amphipathic peptides.

PMID- 28450046
TI  - Pulmonary surfactant and nanocarriers: Toxicity versus combined nanomedical
      applications.
AB  - Pulmonary surfactant is a membrane-based lipid-protein system essential for the
      process of breathing, which coats and stabilizes the whole respiratory surface
      and possesses exceptional biophysical properties. It constitutes the first
      barrier against the entry of pathogens and harmful particles in the alveolar
      region, extended through the lungs, but on the other hand, it can offer novel
      possibilities as a shuttle for the delivery of drugs and nanocarriers. The
      advances in nanotechnology are opening the doors to new diagnostic and
      therapeutic avenues, which are not accessible by means of the current approaches.
      In this context, the pulmonary route is called to become a powerful way of entry
      for innovative treatments based on nanotechnology. In this review, the anatomy of
      the respiratory system and its properties for drug entry are first revisited, as
      well as some current strategies that use the respiratory route for both local and
      peripheral action. Then, a brief overview is presented on what pulmonary
      surfactant is, how it works and why it could be used as a drug delivery vehicle.
      Finally, the review is closed with a description of the development of
      nanocarriers in the lung context and their interaction with endogenous and
      clinical pulmonary surfactants. This article is part of a Special Issue entitled:
      Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba.

PMID- 28450049
TI  - Survival, physical and physiological changes of Taenia hydatigena eggs under
      different conditions of water stress.
AB  - Taenia hydatigena eggs were investigated for morphological and physiological
      changes under water stress conditions. Fresh eggs were exposed at 31%, 47% and
      89% of relative humidity (RH), and survival, size and ultrastructural changes
      were accounted up to 365 days of exposition. The article shows how each RH
      environment affects the vitality of the eggs. Results of this study suggest that
      T. hydatigena eggs have mechanisms to withstand water stress, indicating that the
      eggs clustering improves protection against desiccation, and that endogenous
      metabolism using triacylglycerols play an important role in the maintenance of
      embryo vitality under low, medium and high relative humidity conditions. This
      contributes to understanding the water stress resistance mechanism in eggs
      belonging to Taeniidae family. The findings shown herein have provided a basis to
      better comprehend basic biology and epidemiology of the cysticercosis caused by
      T. hydatigena.

PMID- 28450048
TI  - Liraglutide alleviates H2O2-induced retinal ganglion cells injury by inhibiting
      autophagy through mitochondrial pathways.
AB  - Retinal ganglion cells (RGCs), which exist in the inner retina, are the retinal
      neurons which can be damaged in the early stage of diabetic retinopathy (DR).
      Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, exerts biological
      functions by binding the receptor (GLP-1R), the expression of which in RGC-5
      cells was first shown by our team in 2012. It was reported that liraglutide
      prevented retinal neurodegeneration in diabetic subjects. However, the
      involvement of mechanisms such as autophagy and mitochondrial balance in
      liraglutide-induced retinal protection is unknown. Here, we aimed to investigate
      the protective effects of liraglutide and explore the potential mechanisms of
      liraglutide-induced retinal RGC protection. RGC-5 cells were treated with H2O2
      and/or liraglutide. Cell viability was detected with the CCK-8 kit. The axon
      marker GAP43, autophagy and mitophagy indicators LC3A/B, Beclin-1, p62, Parkin,
      BCL2/Adenovirus E1B 19kDa protein-interacting protein 3-like (BNIP3L) and the key
      regulator of mitochondrial biogenesis PGC-1alpha were examined via western blot
      analysis. Autophagy was also evaluated using the ImageXpress Micro XLS system and
      transmission electron microscopy (TEM). Reactive oxygen species (ROS),
      mitochondrial membrane potential and fluorescent staining for mitochondria were
      also measured using the ImageXpress Micro XLS system. Our results showed that
      pretreatment with liraglutide significantly prevented H2O2-induced cell viability
      decline, mitochondrial morphological deterioration and induction of autophagy,
      which appeared as increased expression of LC3 II/I and Beclin-1, along with p62
      degradation. Moreover, liraglutide suppressed the H2O2-induced decline in GAP43
      expression, thus protecting cells. However, rapamycin induced autophagy and
      blocked the protective process. Liraglutide also provided mitochondrial
      protection and appeared to alleviate H2O2-induced ROS overproduction and a
      decline in mitochondrial membrane potential, partially by promoting mitochondrial
      generation and attenuating mitophagy. In conclusion, liraglutide attenuates H2O2
      induced RGC-5 cell injury by inhibiting autophagy through maintaining a balance
      between mitochondrial biogenesis and mitophagy.

PMID- 28450050
TI  - Transgenic human embryonic stem cells overexpressing FGF2 stimulate
      neuroprotection following spinal cord ventral root avulsion.
AB  - Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to
      neuronal loss, as well as to synaptic detachment. To overcome the degenerative
      effects of VRA, treatments with neurotrophic factors and stem cells have been
      proposed. Thus, we investigated neuroprotection elicited by human embryonic stem
      cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2),
      on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and
      hESC/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal
      cords were processed to evaluate neuronal survival, synaptic stability, and glial
      reactivity two weeks post lesion. Then, qRT-PCR was used to assess gene
      expression of beta2-microglobulin (beta2m), TNFalpha, IL1beta, IL6 and IL10 in
      the spinal cord in vivo and FGF2 mRNA levels in hESC in vitro. The results
      indicate that hESC overexpressing FGF2 significantly rescued avulsed motoneurons,
      preserving synaptic covering and reducing astroglial reactivity. The cells were
      also shown to express BDNF and GDNF at the site of injury. Additionally,
      engraftment of hESC led to a significant reduction in mRNA levels of TNFalpha at
      the spinal cord ventral horn, indicating their immunomodulatory properties.
      Overall, the present data suggest that hESC overexpressing FGF2 are
      neuroprotective and can shift gene expression towards an anti-inflammatory
      environment.

PMID- 28450051
TI  - The value of troponin during an episode of acute heart failure in emergency
      department. One more reason to request it.

PMID- 28450047
TI  - Signaling pathways regulating blood-tissue barriers - Lesson from the testis.
AB  - Signaling pathways that regulate blood-tissue barriers are important for studying
      the biology of various blood-tissue barriers. This information, if deciphered and
      better understood, will provide better therapeutic management of diseases
      particularly in organs that are sealed by the corresponding blood-tissue barriers
      from systemic circulation, such as the brain and the testis. These barriers block
      the access of antibiotics and/or chemotherapeutical agents across the
      corresponding barriers. Studies in the last decade using the blood-testis barrier
      (BTB) in rats have demonstrated the presence of several signaling pathways that
      are crucial to modulate BTB function. Herein, we critically evaluate these
      findings and provide hypothetical models regarding the underlying mechanisms by
      which these signaling molecules/pathways modulate BTB dynamics. This information
      should be carefully evaluated to examine their applicability in other tissue
      barriers which shall benefit future functional studies in the field. This article
      is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude
      Herve.

PMID- 28450052
TI  - Chromatic blur perception in the presence of luminance contrast.
AB  - Hel-Or showed that blurring the chromatic but not the luminance layer of an image
      of a natural scene failed to elicit any impression of blur. Subsequent studies
      have suggested that this effect is due either to chromatic blur being masked by
      spatially contiguous luminance edges in the scene (Journal of Vision 13 (2013)
      14), or to a relatively compressed transducer function for chromatic blur
      (Journal of Vision 15 (2015) 6). To test between the two explanations we
      conducted experiments using as stimuli both images of natural scenes as well as
      simple edges. First, we found that in color-and-luminance images of natural
      scenes more chromatic blur was needed to perceptually match a given level of blur
      in an isoluminant, i.e. colour-only scene. However, when the luminance layer in
      the scene was rotated relative to the chromatic layer, thus removing the colour
      luminance edge correlations, the matched blur levels were near equal. Both
      results are consistent with Sharman et al.'s explanation. Second, when observers
      matched the blurs of luminance-only with isoluminant scenes, the matched blurs
      were equal, against Kingdom et al.'s prediction. Third, we measured the perceived
      blur in a square-wave as a function of (i) contrast (ii) number of luminance
      edges and (iii) the relative spatial phase between the colour and luminance
      edges. We found that the perceived chromatic blur was dependent on both relative
      phase and the number of luminance edges, or dependent on the luminance contrast
      if only a single edge is present. We conclude that this Hel-Or effect is largely
      due to masking of chromatic blur by spatially contiguous luminance edges.

PMID- 28450053
TI  - Water and fluid intake in the prevention and treatment of functional constipation
      in children and adolescents: is there evidence?
AB  - OBJECTIVE: To study the evidence on the role of water and fluid intake in the
      prevention and treatment of functional intestinal constipation in children and
      adolescents. SOURCE OF DATA: A search was carried out in the Medline database
      (between 1966 and 2016) for all published articles containing the following
      words: constipation, water, and fluids, published in Portuguese, English, and
      Spanish. All original articles that assessed children and adolescents were
      selected by title and abstract. The references of these articles were also
      evaluated. SYNTHESIS OF DATA: A total of 1040 articles were retrieved. Of these,
      24 were selected for reading. The study included 11 articles that assessed
      children and adolescents. The articles were divided into two categories, those
      that evaluated water and fluid intake as a risk factor for intestinal
      constipation and those that evaluated their role in the treatment of intestinal
      constipation. Five articles were included in the first category. The criteria for
      assessing fluid intake and bowel rhythm were different in each study. Three
      studies demonstrated an association between low fluid intake and intestinal
      constipation. Regarding treatment, five articles with heterogeneous methodologies
      were found. None of them clearly identified the favorable role of fluid intake in
      the treatment of intestinal constipation. CONCLUSION: There are few articles on
      the association between fluid intake and intestinal constipation. Epidemiological
      evidence indicates an association between lower fluid intake and intestinal
      constipation. Further clinical trials and epidemiological studies that consider
      the international recommendations for fluid intake by children and adolescents
      are required.

PMID- 28450054
TI  - Hyperuricemia is associated with low cardiorespiratory fitness levels and excess
      weight in schoolchildren.
AB  - OBJECTIVE: To evaluate the possible association between hyperuricemia and
      cardiorespiratory fitness levels/nutritional profile, grouped into a single
      variable, in schoolchildren. METHOD: Cross-sectional study of 2335 students from
      Elementary schools, aged 7-17 years of both genders, stratified by conglomerates
      of a municipality in Southern Brazil. Body mass index (BMI) was calculated and
      cardiorespiratory fitness (CRF) was assessed by the 6-minute run/walk test. The
      BMI and CRF were grouped into a single variable, considering: (1) low and normal
      weight/fit; (2) low and normal weight/unfit; (3) overweight-obesity/fit; (4)
      overweight-obesity/unfit. The Poisson regression (prevalence ratio, PR) was used
      for the association between hyperuricemia and BMI/CRF ratio with 95% confidence
      intervals and differences were considered significant when p<0.05. RESULTS: There
      is an association, although subtle, between the presence of hyperuricemia with
      low levels of CRF and the presence of excess weight, when grouped into a single
      variable. Boys and girls with this condition have higher prevalence of
      hyperuricemia (PR: 1.07; p=0.007 for boys; PR: 1.10; p<0.001 for girls).
      CONCLUSION: Together, excess weight and low levels of cardiorespiratory fitness
      are associated with the presence of hyperuricemia in schoolchildren.

PMID- 28450055
TI  - John Michael Thresh, Founding Father of Plant Virus Epidemiology: A tribute.

PMID- 28450056
TI  - Mismatch negativity in bipolar disorder: A neurophysiological biomarker of
      intermediate effect?
AB  - The event-related potential, mismatch negativity (MMN), has been touted as a
      robust and specific neurophysiological biomarker of schizophrenia. Earlier
      studies often included bipolar disorder (BD) as a clinical comparator and
      reported that MMN was significantly impaired only in schizophrenia. However, with
      the increasing number of MMN studies of BD (with larger sample sizes), the
      literature is now providing somewhat consistent evidence of this biomarker also
      being perturbed in BD, albeit to a lesser degree than that observed in
      schizophrenia. Indeed, two meta-analyses have now shown that the effect sizes in
      BD samples suggest a moderate impairment in MMN, compared to the large effect
      sizes shown in schizophrenia. Pharmacologically, MMN is an extremely useful non
      invasive probe of glutamatergic (more specifically, N-methyl-d-aspartate [NMDA]
      receptor) disturbances and this system has been implicated in the pathophysiology
      of both schizophrenia and BD. Therefore, it may be best to conceptualize/utilize
      MMN as an index of a psychopathology that is shared across psychotic and related
      disorders, rather than being a diagnosis-specific biomarker. More research is
      needed, particularly longitudinal designs including studies that assess MMN over
      an individual's life course and then examine NMDA receptor expression/binding
      post-mortem. At this point and despite a disproportionate amount of research, the
      current evidence suggests that with respect to BD, MMN is a neurophysiological
      biomarker of intermediate effect. With replication and validation of this effect,
      MMN may prove to be an important indicator of a common psychopathology shared by
      a significant proportion of individuals with schizophrenia and bipolar spectrum
      illnesses.

PMID- 28450057
TI  - Environmental neurotoxicant manganese regulates exosome-mediated extracellular
      miRNAs in cell culture model of Parkinson's disease: Relevance to alpha-synuclein
      misfolding in metal neurotoxicity.
AB  - Many chronic neurodegenerative disorders share a common pathogenic mechanism
      involving the aggregation and deposition of misfolded proteins. Recently, it was
      shown that these aggregated proteins could be transferred from one cell to
      another via extracellular nanovesicles called exosomes. Initially thought to be a
      means of cellular waste removal, exosomes have since been discovered to actively
      participate in cell-to-cell communication. Importantly, various inflammatory and
      signaling molecules, as well as small RNAs are selectively packaged in these
      vesicles. Considering the important role of environmental manganese (Mn) in
      Parkinson's disease (PD)-like neurological disorders, we characterized the effect
      of Mn on exosome content and release using an MN9D dopaminergic cell model of PD,
      which was generated to stably express wild-type human alpha-synuclein (alphaSyn).
      Mn exposure (300MUM MnCl2) for 24h induced the release of exosomes into the
      extracellular media prior to cytotoxicity, as determined by NanoSight particle
      analysis and electron microscopy. Strikingly, Western blot analysis revealed that
      Mn treatment in alphaSyn-expressing cells increases the protein Rab27a, which
      regulates the release of exosomes from cells. Moreover, next-generation
      sequencing showed more small RNAs in exosomes isolated from Mn-exposed cells than
      from control exosomes. Our miRNA profiling analysis led to the discovery of
      increased expression of certain miRNAs previously shown to regulate key
      biological pathways, including protein aggregation, autophagy, inflammation and
      hypoxia. Collectively, our results provide a glimpse of Mn's role in modulating
      extracellular miRNA content through exosomal release from dopaminergic neuronal
      cells and thus potentially contributing to progressive neurodegeneration. Further
      characterization of extracellular miRNAs and their targets will have major
      impacts on biomarker discovery and translational strategies for environmentally
      linked neurodegenerative diseases including PD.

PMID- 28450058
TI  - Inhibition of hepatitis B virus replication by N-hydroxyisoquinolinediones and
      related polyoxygenated heterocycles.
AB  - We previously reported low sensitivity of the hepatitis B virus (HBV)
      ribonuclease H (RNaseH) enzyme to inhibition by N-hydroxyisoquinolinedione (HID)
      compounds. Subsequently, our biochemical RNaseH assay was found to have a high
      false negative rate for predicting HBV replication inhibition, leading to
      underestimation of the number of HIDs that inhibit HBV replication. Here, 39 HID
      compounds and structurally related polyoxygenated heterocycles (POH), N
      hydroxypyridinediones (HPD), and flutimides were screened for inhibition of HBV
      replication in vitro. Inhibiting the HBV RNaseH preferentially blocks synthesis
      of the positive-polarity DNA strand and causes accumulation of RNA:DNA
      heteroduplexes. Eleven HIDs and one HPD preferentially inhibited HBV positive
      polarity DNA strand accumulation. EC50s ranged from 0.69 MUM to 19 MUM with
      therapeutic indices from 2.4 to 71. Neither the HIDs nor the HPD had an effect on
      the ability of the polymerase to elongate DNA strands in capsids. HBV RNaseH
      inhibition by the HIDs was confirmed with an improved RNaseH assay and by
      detecting accumulation RNA:DNA heteroduplexes in HBV capsids from cells treated
      with a representative HID. Therefore, the HID scaffold is more promising for anti
      HBV drug discovery than we originally reported, and the HPD scaffold may hold
      potential for antiviral development. The preliminary structure-activity
      relationship will guide optimization of the HID/HPDs as HBV inhibitors.

PMID- 28450059
TI  - Epidermal iron metabolism for iron salvage.
AB  - BACKGROUND: The epidermis shows a reverse iron gradient from the basal layer to
      the stratum corneum and consequently, little epidermal intracellular iron is lost
      by desquamation. OBJECTIVE: To clarify the underlying mechanism of iron salvage.
      METHODS: We first used immunohistochemistry and mRNA quantification to
      demonstrate the distinctive expression pattern of iron metabolism molecules. The
      obtained results were confirmed using normal human epidermal keratinocytes
      (NHEKs) during in vitro differentiation. We next examined the effects of reducing
      ferroportin expression in vitro by ferroportin-specific siRNAs or hepcidin on the
      intracellular iron content of cultured NHEKs. Finally, we compared epidermal and
      systemic iron metabolism between FpnEpi-KO mice and control mice. RESULTS: The
      results of both mRNA and protein expression analysis showed that most molecules
      participating in iron import and storage were expressed in the lower epidermis,
      while those involved in iron release from heme or iron transport were expressed
      in the upper epidermis. Consistent with their expression, keratinocyte
      differentiation reduced intracellular iron content. We next demonstrated that
      reducing ferroportin expression in vitro by ferroportin-specific siRNAs or
      hepcidin significantly increased the intracellular iron content. Finally, we
      showed that the iron content of the epidermis and squames was significantly
      greater in FpnEpi-KO mice than in control mice, and that FpnEpi-KO exhibited a
      more rapid decrease in blood hemoglobin concentration than control mice on a low
      iron diet. CONCLUSION: These studies demonstrated that the epidermis is equipped
      with a machinery by which intracellular iron in differentiated keratinocytes is
      excreted to the extracellular space before reaching the stratum corneum.

PMID- 28450061
TI  - Morphine dosing strategy plays a key role in the generation and duration of the
      produced antinociceptive tolerance.
AB  - Antinociceptive tolerance after repetitive administration of morphine severely
      limits its clinical use. Despite increased mechanistic understanding of morphine
      tolerance, little is known about the influence of dosing regimens in its
      development. We hypothesized that the starting dose of morphine, dosing frequency
      and dose increments, influence antinociception and the manifestation of
      antinociceptive tolerance in rats. Male rats were randomly divided into four
      groups with different intermittent starting-doses of daily morphine (b.i.d.)
      followed by different increments of single-dose morphine upon development of
      antinociceptive tolerance, for 2-3 weeks: 2.5 (b.i.d.)->5 -> 10->15 mg/kg/day, 5
      (b.i.d.)->10 mg/kg/day, 5 (b.i.d.)->15 mg/kg/day, 10 (b.i.d.)->20 mg/kg/day.
      Antinociception was assessed daily pre-treatment and at several time-points over
      2 h post-administration, using tail-flick and hot-plate assays. Tolerance was
      defined as significant antinociceptive desensitization and was presented as
      significant reduction of the maximum and total antinociceptive efficacy upon
      morphine administration. Rats commenced on 2.5 mg/kg/day (b.i.d.) morphine
      developed tolerance faster than those started on 5 or 10 mg/kg/day (b.i.d.).
      Comparatively, higher starting and maintenance doses of morphine produced
      prolonged antinociception and delayed tolerance. Whereas, lower starting and
      maintenance doses of morphine produced less total antinociception during the
      course of treatment and did not delay the onset of tolerance, but require smaller
      dose-increments to reach antinociception after development of antinociceptive
      tolerance. These results suggest that morphine starting dose, dosing frequency,
      increments and timing determine the manifestation of antinociceptive tolerance
      and extent of antinociception. In addition, our results also highlight the need
      for generally standardized and validated assay protocols and procedures to
      compare different studies, as a prerequisite to translate pre-clinical results
      into the clinic.

PMID- 28450060
TI  - Endocannabinoid modulation of dopamine neurotransmission.
AB  - Dopamine (DA) is a major catecholamine neurotransmitter in the mammalian brain
      that controls neural circuits involved in the cognitive, emotional, and motor
      aspects of goal-directed behavior. Accordingly, perturbations in DA
      neurotransmission play a central role in several neuropsychiatric disorders.
      Somewhat surprisingly given its prominent role in numerous behaviors, DA is
      released by a relatively small number of densely packed neurons originating in
      the midbrain. The dopaminergic midbrain innervates numerous brain regions where
      extracellular DA release and receptor binding promote short- and long-term
      changes in postsynaptic neuron function. Striatal forebrain nuclei receive the
      greatest proportion of DA projections and are a predominant hub at which DA
      influences behavior. A number of excitatory, inhibitory, and modulatory inputs
      orchestrate DA neurotransmission by controlling DA cell body firing patterns,
      terminal release, and effects on postsynaptic sites in the striatum. The
      endocannabinoid (eCB) system serves as an important filter of afferent input that
      acts locally at midbrain and terminal regions to shape how incoming information
      is conveyed onto DA neurons and to output targets. In this review, we aim to
      highlight existing knowledge regarding how eCB signaling controls DA neuron
      function through modifications in synaptic strength at midbrain and striatal
      sites, and to raise outstanding questions on this topic. This article is part of
      the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".

PMID- 28450063
TI  - Diverticulitis Diagnosed in the Emergency Room: Is It Safe to Discharge Home?
AB  - BACKGROUND: Inpatient treatment of patients with colon diverticulitis represents
      a significant financial and clinical burden to the health care system and
      patients. The aim of this study was to compare patients with diverticulitis in
      the emergency department (ED), who were discharged to home vs admitted to the
      hospital. STUDY DESIGN: We reviewed all patients evaluated in the ED of a
      metropolitan health system, with the primary diagnosis of diverticulitis (ICD-9
      562.11), from 2010 through 2012. Only patients diagnosed with CT and those with
      follow-up were included. RESULTS: We identified 240 patients; 132 (55%) were
      women and mean age was 59.1 years (SD 16.1 years). Imaging findings included
      extraluminal air (21%), pericolic or pelvic abscess (12%), free fluid (16%), and
      pneumoperitoneum (6%). One hundred forty-four (60%) were admitted to the hospital
      and 96 (40%) were discharged to home on oral antibiotics. Patients admitted to
      the hospital were more likely to be older than 65 years (p = 0.0007), have a
      Charlson comorbidity score >= 2 (p = 0.0025), to be on steroids or
      immunosuppression (p = 0.0019), and have extraluminal air (p < 0.0001) or
      diverticular abscess (p < 0.0001) on imaging. Median follow-up for all patients
      was 36.5 months (interquartile range 25.2 to 43 months). Among patients
      discharged from the ED, 12.5% returned to the ED or were readmitted within 30
      days, with only 1 patient (1%) requiring emergency surgery, but not until 20
      months later. Patients admitted to the hospital had similar rates of readmission
      (15%; p = 0.65). CONCLUSIONS: Patients diagnosed with uncomplicated
      diverticulitis in the emergency room can be safely discharged home on oral
      antibiotics, as long as CT findings are included in the decision-making process.
      Patients with complicated diverticulitis on CT scan should be admitted to the
      hospital with surgical consultation.

PMID- 28450062
TI  - Laparoscopic vs Robotic Intraperitoneal Mesh Repair for Incisional Hernia: An
      Americas Hernia Society Quality Collaborative Analysis.
AB  - BACKGROUND: Robotic intraperitoneal mesh placement (rIPOM) has emerged recently
      as an alternative to laparoscopic intraperitoneal mesh placement (LapIPOM) for
      minimally invasive incisional hernia repair. We aimed to compare LapIPOM with
      rIPOM in terms of hospital length of stay (LOS) and 30-day postoperative
      complications in patients undergoing incisional hernia repair within the Americas
      Hernia Society Quality Collaborative. STUDY DESIGN: Propensity score analysis was
      used to compare matched groups of patients within the Americas Hernia Society
      Quality Collaborative undergoing LapIPOM vs rIPOM. The primary outcomes measure
      was hospital LOS and secondary outcomes were 30-day wound events. RESULTS: Four
      hundred and fifty-four (71.9%) patients underwent LapIPOM and 177 (28.1%)
      underwent rIPOM. The laparoscopic group had an increased median LOS (1 vs 0 days;
      interquartile range 3.00; p < 0.001). The risk of surgical site occurrence was
      higher in the LapIPOM group vs the rIPOM group (14% vs 5%; p = 0.001); however,
      surgical site occurrence requiring procedural intervention was similar between
      the groups (1% vs 0%; p = 1). Operative time longer than 2 hours was more common
      in the rIPOM group (47% vs 31%; p < 0.05). CONCLUSIONS: Despite longer operative
      times using the rIPOM approach, patients undergoing rIPOM had a significantly
      shorter LOS than LapIPOM, without additional risk of wound morbidity requiring
      intervention. Additional studies are necessary to identify the best candidates
      for the rIPOM approach.

PMID- 28450064
TI  - A paradoxical response of the rat organism to long-term inhalation of silica
      containing submicron (predominantly nanoscale) particles of a collected
      industrial aerosol at realistic exposure levels.
AB  - While engineered SiO2 nanoparticle toxicity is being widely investigated, mostly
      on cell lines or in acute animal experiments, the practical importance of as well
      as the theoretical interest in industrial condensation aerosols with a high SiO2
      particle content seems to be neglected. That is why, to the best of our
      knowledge, long-term inhalation exposure to nano-SiO2 has not been undertaken in
      experimental nanotoxicology studies. To correct this data gap, female white rats
      were exposed for 3 or 6 months 5 times a week, 4h a day to an aerosol containing
      predominantly submicron (nanoscale included) particles of amorphous silica at an
      exposure concentration of 2.6+/-0.6 or 10.6+/-2.1mg/m3. This material had been
      collected from the flue-gas ducts of electric ore smelting furnaces that were
      producing elemental silicon, subsequently sieved through a<2MUm screen and
      redispersed to feed a computerized "nose only" inhalation system. In an auxiliary
      experiment using a single-shot intratracheal instillation of these particles, it
      was shown that they induced a pulmonary cell response comparable with that of a
      highly cytotoxic and fibrogenic quartz powder, namely DQ12. However, in long-term
      inhalation tests, the aerosol studied proved to be of very low systemic toxicity
      and negligible pulmonary fibrogenicity. This paradox may be explained by a low
      SiO2 retention in the lungs and other organs due to the relatively high
      solubility of these nanoparticles. nasal penetration of nanoparticles into the
      brain as well as their genotoxic action were found in the same experiment,
      results that make one give a cautious overall assessment of this aerosol as an
      occupational or environmental hazard.

PMID- 28450065
TI  - Social inequalities and dental caries in six-year-old children from the
      Netherlands.
AB  - OBJECTIVES: The purpose of our study was to investigate the association of
      different socioeconomic and sociodemographic factors with dental caries in six
      year-old children. Furthermore, we applied a district based approach to explore
      the distribution of dental caries among districts of low and high socioeconomic
      position (SEP). METHODS: In our cross-sectional study 5189 six-year-olds were
      included. This study was embedded in a prospective population-based birth cohort
      study in Rotterdam, the Netherlands, the Generation R Study. Parental education
      level, parental employment status, net household income, single parenting, and
      teenage pregnancy were considered as indicators for SEP. Dental caries was scored
      on intraoral photographs by using the decayed, missing, and filled teeth (dmft)
      index. We compared children without caries (dmft=0) to children with mild caries
      (dmft=1-3) or severe caries (dmft >3). Multinomial logistic regression analyses
      and binary logistic regression analyses were performed to study the association
      between SEP and caries, and between district and caries, respectively. RESULTS:
      Only maternal education level remained significantly associated with mild caries
      after adjusting for all other SEP-indicators. Paternal educational level,
      parental employment status, and household income additionally served as
      independent indicators of SEP in children with severe caries. Furthermore, living
      in more disadvantaged districts was significantly associated with higher odds of
      dental caries. CONCLUSION: Dental caries is more prevalent among six-year-old
      children with a low SEP, which is also visible at the district level. Maternal
      educational level is the most important indicator of SEP in the association with
      caries. CLINICAL SIGNIFICANCE: Our results should raise concerns about the
      existing social inequalities in dental caries and should encourage development of
      dental caries prevention strategies. New knowledge about the distribution of oral
      health inequalities between districts should be used to target the right audience
      for these strategies.

PMID- 28450067
TI  - Fibroblast-Derived Clusterin Negatively Regulates Pigmentation.

PMID- 28450066
TI  - Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease
      Activity in Morphea.
AB  - IFN-related pathways have not been studied in morphea, and biomarkers are needed.
      We sought to characterize morphea serum cytokine imbalance and IFN-related gene
      expression in blood and skin to address this gap by performing a case-control
      study of 87 participants with morphea and 26 healthy control subjects. We used
      multiplexed immunoassays to determine serum cytokine concentrations, performed
      transcriptional profiling of whole blood and lesional morphea skin, and used
      double-staining immunohistochemistry to determine the cutaneous cellular source
      of CXCL9. We found that CXCL9 was present at increased concentrations in morphea
      serum (P < 0.0001), as were other T helper type 1 cytokines. CXCL9 serum
      concentration correlated with the modified Localized Scleroderma Skin Severity
      Index (r = 0.44, P = 0.0001), a validated measure of disease activity. CXCL9 gene
      expression was also increased in inflammatory lesional morphea skin (fold change
      = 30.6, P = 0.006), and preliminary transcriptional profiling showed little
      evidence for IFN signature in whole blood. Double-staining immunohistochemistry
      showed CXCL9 co-localized with CD68+ dermal macrophages. In summary, inflammatory
      morphea is characterized by T helper type 1 cytokine imbalance in serum,
      particularly CXCL9, which is associated with disease activity. CXCL9 expression
      in lesional macrophages implicates the skin as the source of circulating
      cytokines. CXCL9 is a promising biomarker of disease activity in morphea.

PMID- 28450068
TI  - A theoretical analysis of anatomical and functional intestinal slow wave re
      entry.
AB  - Intestinal bioelectrical slow waves are a key regulator of intestinal motility.
      Peripheral pacemakers, ectopic initiations and sustained periods of re-entrant
      activities have all been experimentally observed to be important factors in
      setting the frequency of intestinal slow waves, but the tissue-level mechanisms
      underpinning these activities are unclear. This theoretical analysis aimed to
      define the initiation, maintenance, and termination criteria of two classes of
      intestinal re-entrant activities: anatomical re-entry and functional re-entry.
      Anatomical re-entry was modeled in a three-dimensional (3D) cylindrical model,
      and functional rotor was modeled in a 2D rectangle model. A single-pulse stimulus
      was used to invoke an anatomical re-entry and a prolonged refractory block was
      used to invoke the rotor. In both cases, the simulated re-entrant activities
      operated at frequencies above the baseline entrainment frequency. The anatomical
      re-entry simulation results demonstrated that a temporary functional refractory
      block would be required to initiate the re-entrant activity in a single direction
      around the cylindrical model. The rotor could be terminated by a single-pulse
      stimulus delivered around the core of the rotor. In conclusion, the simulation
      results provide the following new insights into the mechanisms of intestinal re
      entry: (i) anatomical re-entry is only maintained within a specific range of
      velocities, outside of which the re-entrant activities become either an ectopic
      activity or simultaneous activations of the intestinal wall; (ii) a maintained
      rotor entrained slow waves faster in the antegrade direction than in the
      retrograde direction. Simulations are shown to be a valuable tool for achieving
      novel insights into the mechanisms of intestinal slow wave dysrhythmia.

PMID- 28450069
TI  - Circulating steroids negatively correlate with tinnitus.
AB  - While not a disease entity in itself; symptoms of tinnitus (from Latin tinnio -
      clink) accompany a number of diseases. Tinnitus prevalence increases with age,
      deteriorates one's quality of life, and may even result in suicidal behavior.
      Tinnitus develops in response to a variety of risk factors, otoxic substances,
      noise exposure, hearing disorders, and psychological alterations. Tinnitus is
      closely related to mood, depression, and psychological state. In the present
      study, we focused on alterations of the steroid metabolome and particularly
      neuroactive, neuroprotective, and immunomodulatory steroids in patients with
      tinnitus. The study group consisted of 28 patients without evidence of an organic
      cause of tinnitus as well as without associated diseases or the effect of
      ototoxic medications. All patients underwent a complete audiological assessment
      and laboratory tests including routine biochemical markers and quantification of
      circulating steroids using gas chromatography/mass spectrometry and immunoassays.
      To rule out a pathology in the cerebellopontine angle area, CT scan or MRI were
      performed. To diagnose stem lesions, evoked potentials were also measured.
      Pearson's correlations and multivariate regression were used to assess any links
      between tinnitus intensity and frequency on the one hand, and steroid levels on
      the other. Results indicated a significant and consistent negative correlation
      between tinnitus indices and intensity of adrenal steroidogenesis. The
      circulating steroid metabolome including hormones and neuroactive,
      neuroprotective, and immunomodulatory steroids negatively correlates with the
      degree of tinnitus due to hypothalamo-pituitary-adrenal axis malfunction. Our
      results may help explain the pathophysiology of tinnitus and improve its
      diagnosis. However, further studies are needed to verify our postulation.

PMID- 28450070
TI  - Synthesis of androstene oxime-nitrogen mustard bioconjugates as potent
      antineoplastic agents.
AB  - In the present study, synthesis and antineoplastic activity of phenylacetic acid
      and benzoic acid nitrogen mustard conjugates of various steroidal oximes are
      reported for the first time. The conjugation was achieved through a more stable
      oxime-ester linkage and the resulting newly synthesized conjugates were evaluated
      in vitro on various human cancer cell lines for cytotoxicity. The extent of their
      alkylating activity was investigated by the in vitro colorimetric 4-(p
      nitrobenzyl)pyridine (NBP) assay. The 17E-steroidal oxime-benzoic acid mustard
      ester 3beta-acetoxy-17E-[p-(N,N-bis(2-chloroethyl)amino)]benzoyloxyimino-androst
      5-ene (8) emerged as the most potent conjugate having significant cytotoxicity on
      most of the NCI 60-cell lines. Outstanding growth inhibition was observed on the
      IGROV1 ovarian cancer cell line with GI50=0.937uM. In general, the D-ring derived
      androstene oxime-nitrogen mustard conjugates were found to possess better
      antineoplastic activity over a variety of cancer cells in comparison to those
      derived from other rings of the steroid skeleton.

PMID- 28450071
TI  - Good cell culture practices &in vitro toxicology.
AB  - Good Cell Culture Practices (GCCP) is of high relevance to in vitro toxicology.
      The European Society of Toxicology In Vitro (ESTIV), the Center for Alternatives
      for Animal Testing (CAAT) and the In Vitro Toxicology Industrial Platform (IVTIP)
      joined forces to address by means of an ESTIV 2016 pre-congress session the
      different aspects and applications of GCCP. The covered aspects comprised the
      current status of the OECD guidance document on Good In Vitro Method Practices,
      the importance of quality assurance for new technological advances in in vitro
      toxicology including stem cells, and the optimized implementation of Good
      Manufacturing Practices and Good Laboratory Practices for regulatory testing
      purposes. General discussions raised the duality related to the difficulties in
      implementing GCCP in an academic innovative research framework on one hand, and
      on the other hand, the need for such GCCP principles in order to ensure
      reproducibility and robustness of in vitro test methods for toxicity testing.
      Indeed, if good cell culture principles are critical to take into consideration
      for all uses of in vitro test methods for toxicity testing, the level of
      application of such principles may depend on the stage of development of the test
      method as well as on the applications of the test methods, i.e., academic
      innovative research vs. regulatory standardized test method.

PMID- 28450072
TI  - Contribution of Clinical Neuroimaging to the Understanding of the Pharmacology of
      Methylphenidate.
AB  - Methylphenidate (MPH) is currently the most widely used molecule in the
      pharmacologic treatment of attention-deficit hyperactivity disorder (ADHD).
      Although experience of its application now extends over several decades, its
      psychotropic nature, prolonged use in children, and chemical relation to
      amphetamines still raise doubts in the minds of prescribers and the families of
      the patients. Brain imaging has shed considerable light on the neuropharmacology
      of MPH. The two main in vivo neuroimaging techniques are positron-emission
      tomography (PET) and magnetic resonance imaging (MRI), and these can be applied
      in both animal models and humans. The present review seeks to show how human
      molecular and functional imaging has contributed to determining not only the
      molecular targets of MPH, and the action kinetics of the various pharmaceutical
      forms available, but also the connectivity and brain networks activated by
      treatment. We also discuss the perspectives opened up by new hybrid PET-MRI
      techniques that enable multimodal tracking of the impact of methylphenidate on
      neurotransmission.

PMID- 28450073
TI  - Cerebral magnetic resonance changes associated with fibromyalgia syndrome.
AB  - Fibromyalgia syndrome is a chronic disease, of unknown origin, whose diagnostic
      criteria were established in 1990 by the American College of Rheumatology. New
      criteria were proposed in 2010 that have not yet been validated. It is
      characterized by a generalized chronic musculoskeletal pain, accompanied by
      hyperalgesia and allodynia, as well as other motor, vegetative, cognitive and
      affective symptoms and signs. We have reviewed a set of studies with cerebral
      magnetic resonance (morphometry, connectivity and spectroscopy) that refer to
      changes in areas involved in pain processing. Modifications in gray and white
      matter volume, as well as in levels of N-acetylaspartate, choline or glutamate,
      among other metabolites, have been observed in the hippocampus, insula,
      prefrontal and cingular cortex. Neuroradiological findings are nonspecific and
      similar to those found in other examples of chronic pain. An increase in the
      sample size and a standardized methodology would facilitate comparison, allowing
      the drawing of general conclusions.

PMID- 28450074
TI  - Structural Basis of MeCP2 Distribution on Non-CpG Methylated and
      Hydroxymethylated DNA.
AB  - The Rett-syndrome-associated methyl-CpG-binding protein 2 (MeCP2) selectively
      binds methylated DNA to regulate transcription during the development of mature
      neurons. Like other members of the methyl-CpG-binding domain (MBD) family, MeCP2
      functions through the recognition of symmetrical 5-methylcytosines in CpG (mCG)
      dinucleotides. Advances in base-level resolution epigenetic mapping techniques
      have revealed, however, that MeCP2 can bind asymmetrically methylated and
      hydroxymethylated CpA dinucleotides and that this alternative binding selectivity
      modifies gene expression in the developing mammalian brain. The structural
      determinants of binding to methylated CpA (mCA) and hydroxymethylated DNA have
      not been previously investigated. Here, we employ isothermal titration
      calorimetry and NMR spectroscopy to characterize MeCP2 binding to methylated and
      hydroxymethylated mCG and mCA DNA, examine the effects of Rett-syndrome
      associated missense mutations, and make comparisons to the related and
      evolutionarily most ancient protein, MBD2. These analyses reveal that MeCP2 binds
      mCA with high affinity in a strand-specific and orientation-dependent manner. In
      contrast, MBD2 does not show high affinity or methyl-specific binding to mCA. The
      Rett-associated missense mutations (T158M, R106W, and P101S) destabilize the
      MeCP2 MBD and disrupt the recognition of mCG and mCA equally. Finally,
      hydroxymethylation of a high-affinity mCA site does not alter the binding
      properties, whereas hemi-hydroxylation of the equivalent cytosine in an mCG site
      decreases affinity and specificity. Based on these findings, we suggest that
      MeCP2 recognition of methylated/hydroxymethylated CpA dinucleotides functions as
      an epigenetic switch redistributing MeCP2 among mCG and mCA loci.

PMID- 28450076
TI  - Local energy on demand: Are 'spontaneous' astrocytic Ca2+-microdomains the
      regulatory unit for astrocyte-neuron metabolic cooperation?
AB  - Astrocytes are a neural cell type critically involved in maintaining brain energy
      homeostasis as well as signaling. Like neurons, astrocytes are a heterogeneous
      cell population. Cortical astrocytes show a complex morphology with a highly
      branched aborization and numerous fine processes ensheathing the synapses of
      neighboring neurons, and typically extend one process connecting to blood
      vessels. Recent studies employing genetically encoded fluorescent calcium (Ca2+)
      indicators have described 'spontaneous' localized Ca2+-transients in the
      astrocyte periphery that occur asynchronously, independently of signals in other
      parts of the cells, and that do not involve somatic Ca2+ transients; however,
      neither it is known whether these Ca2+-microdomains occur at or near neuronal
      synapses nor have their molecular basis nor downstream effector(s) been
      identified. In addition to Ca2+ microdomains, sodium (Na+) transients occur in
      astrocyte subdomains, too, most likely as a consequence of Na+ co-transport with
      the neurotransmitter glutamate, which also regulates mitochondrial movements
      locally - as do cytoplasmic Ca2+ levels. In this review, we cover various aspects
      of these local signaling events and discuss how structural and biophysical
      properties of astrocytes might foster such compartmentation. Astrocytes
      metabolically interact with neurons by providing energy substrates to active
      neurons. As a single astrocyte branch covers hundreds to thousands of synapses,
      it is tempting to speculate that these metabolic interactions could occur
      localized to specific subdomains of astrocytes, perhaps even at the level of
      small groups of synapses. We discuss how astrocytic metabolism might be regulated
      at this scale and which signals might contribute to its regulation. We speculate
      that the astrocytic structures that light up transiently as Ca2+-microdomains
      might be the functional units of astrocytes linking signaling and metabolic
      processes to adapt astrocytic function to local energy demands. The understanding
      of these local regulatory and metabolic interactions will be fundamental to fully
      appreciate the complexity of brain energy homeostasis as well as its failure in
      disease and may shed new light on the controversy about neuron-glia bi
      directional signaling at the tripartite synapse.

PMID- 28450077
TI  - Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective
      analysis and future prospects.
AB  - The plastic-adherent, fibroblast-like, clonogenic cells found in the human body
      now defined as multipotent "Mesenchymal Stromal Cells" (MSCs) hold immense
      potential for cell-based therapies. Recently, research and basic knowledge of
      these cells has fast-tracked, both from fundamental and translational
      perspectives. There have been important discoveries with respect to the available
      variety of tissue sources, the development of protocols for their easy isolation
      and in vitro expansion and for directed differentiation into various cell types.
      In addition, there has been discovery of novel abilities such as immune
      modulation and further development of the use of biomaterials to aid isolation,
      expansion and differentiation together with improved delivery to the selected
      optimal tissue site. However, the molecular fingerprint of MSCs in these contexts
      remains imprecise and inadequate. Consequently, without this crucial knowledge it
      is difficult to achieve progress to determine with precision their practical
      developmental potentials. Detailed investigations on the global gene expression,
      or transcriptome, of MSCs could offer essential clues in this regard. In this
      article, we address the challenges associated with MSC transcriptome studies, the
      paradoxes observed in published experimental results and the need for careful
      transcriptomic analysis. We describe the exemplary applications with various
      transcriptome platforms that are used to address the variation in biomarkers and
      the identification of differentiation processes. The evolution and the potentials
      for adapting next-generation sequencing (NGS) technology in transcriptome
      analysis are discussed. Lastly, based on review of the existing understanding and
      published studies, we propose how NGS may be applied to promote further
      understanding of the biology of MSCs and their use in allied fields such as
      regenerative medicine.

PMID- 28450078
TI  - Frontostriatal development and probabilistic reinforcement learning during
      adolescence.
AB  - Adolescence has traditionally been viewed as a period of vulnerability to
      increased risk-taking and adverse outcomes, which have been linked to
      neurobiological maturation of the frontostriatal reward system. However, growing
      research on the role of developmental changes in the adolescent frontostriatal
      system in facilitating learning will provide a more nuanced view of adolescence.
      In this review, we discuss the implications of existing research on this topic
      for learning during adolescence, and suggest that the very neural changes that
      render adolescents vulnerable to social pressure and risky decision making may
      also stand to play a role in scaffolding the ability to learn from rewards and
      from performance-related feedback.

PMID- 28450075
TI  - Congenital Adrenal Hyperplasia.
AB  - The congenital adrenal hyperplasias comprise a family of autosomal recessive
      disorders that disrupt adrenal steroidogenesis. The most common form is due to 21
      hydroxylase deficiency associated with mutations in the 21-hydroxylase gene,
      which is located at chromosome 6p21. The clinical features associated with each
      disorder of adrenal steroidogenesis represent a clinical spectrum that reflect
      the consequences of the specific mutations. Treatment goals include normal linear
      growth velocity and "on-time" puberty in affected children. For adolescent and
      adult women, treatment goals include regularization of menses, prevention of
      progression of hirsutism, and preservation of fertility. For adolescent and adult
      men, prevention and early treatment of testicular adrenal rest tumors is
      beneficial. In this article key aspects regarding pathophysiology, diagnosis, and
      treatment of congenital adrenal hyperplasia are reviewed.

PMID- 28450079
TI  - Sensory system development influences the ontogeny of hippocampal associative
      coding and trace eyeblink conditioning.
AB  - Until recently, it was believed that hippocampal development was the primary rate
      limiting factor in the developmental emergence of hippocampal forms of learning,
      such as trace eyeblink conditioning (EBC). Indeed, hippocampal neuronal activity
      shows an age-related increase in both complexity and task responsiveness during
      trace EBC. However, recent work from our laboratory suggests that sensory system
      development may also play a role. Training with the earlier-developing
      somatosensory system results in an earlier emergence of trace EBC in rats,
      suggesting that the development of sensory input to the hippocampus may influence
      the development of trace EBC. The goal of the current study was to examine the
      activity of hippocampal CA1 pyramidal cells during acquisition of trace EBC with
      an early-developing somatosensory CS. Rat pups were trained with a vibration CS
      on postnatal days (P) 17-19, P21-23, and P24-26 while CA1 pyramidal cell activity
      was recorded. Results indicated that CA1 neurons show an age-related increase in
      responsiveness to trial events. Although the magnitude of neuronal responding
      showed age-related increases in activity, all three age groups demonstrated
      learning-related increases in firing rate magnitude and peaks in firing rate were
      evident both at CS onset and offset. These findings suggest that the ontogeny of
      trace eyeblink conditioning is related to both hippocampal and sensory system
      development.

PMID- 28450081
TI  - A Qualitative Study of What US Parents Say and Do When Their Young Children See
      Pornography.
AB  - OBJECTIVE: There is no empirical information about how parents react when they
      discover that their young children have seen pornography. To address this gap in
      the literature, the current study sought to improve our understanding of parental
      reactions to discovering that their children ages <12 years old have seen
      pornography using a mixed-methods approach. METHODS: A convenience sample of
      participants (N = 279) was recruited from the online survey service Mechanical
      Turk. Eligible participants completed an online survey comprising close-ended and
      open-ended questions about their reactions when their young children saw
      pornography. Qualitative data were analyzed using a content analysis approach.
      RESULTS: Parents had 5 main reactions when realizing that their children had
      viewed pornography: 1) angry, shaming, or punitive; 2) calm and factual; 3)
      ignoring, minimizing, or denying that it happened; 4) panic or fear; and 5) lying
      to the child about what the child viewed. Most parents reacted calmly, while a
      small percentage reported that they hit, scolded, or shamed their young children
      for seeing the pornography. Many reported not knowing what to say or do.
      CONCLUSIONS: Development and evaluation of parental scripts for developmentally
      appropriate parent-child (or pediatrician-child) communication about pornography
      could benefit the field.

PMID- 28450080
TI  - Weak involvement of octopamine in aversive taste learning in a snail.
AB  - The pond snail Lymnaea stagnalis is capable of learning taste aversion by pairing
      presentations of a sucrose solution and an electric shock and consolidating it
      into long-term memory (LTM), which is referred to as conditioned taste aversion
      (CTA). We asked here if the neurotransmitter octopamine is involved in CTA. We
      first determined the levels of octopamine and its catabolites in the central
      nervous system (CNS) of snails with varying degrees of food deprivation, because
      CTA grades are correlated with degrees of food deprivation. We next manipulated
      the octopamine signaling using both an agonist and an antagonist of octopamine
      receptors and correlated their respective effects with CTA grades. We found that
      snails with the least amount of food-deprivation obtained the best CTA grade and
      had low levels of octopamine; whereas the most severely food-deprived snails did
      not form CTA and had the highest CNS octopamine levels. In modestly food-deprived
      snails, octopamine application increased the basal level of feeding response to a
      sucrose solution, and it did not obstruct CTA formation. Application of
      phentolamine, an octopamine receptor antagonist, to the most severely food
      deprived snails decreased the basal level of feeding elicited by sucrose, but it
      did not enhance CTA formation. We conclude that octopamine involvement in CTA
      formation in Lymnaea is at best weak, and that the changes in CNS octopamine
      content are an epiphenomenon.

PMID- 28450082
TI  - Randomized Trial of a Children's Book Versus Brochures for Safe Sleep Knowledge
      and Adherence in a High-Risk Population.
AB  - OBJECTIVE: Sleep-related infant deaths have plateaued in the past decade,
      disproportionately affecting low socioeconomic status (SES) families. Printed
      materials are widely used for anticipatory guidance, yet none for safe sleep has
      been studied. We tested the efficacy of a specially designed children's book
      compared to brochures for safe sleep knowledge and adherence, which we
      hypothesized would be greater due to superior readability and engagement.
      METHODS: This randomized controlled trial involved low-SES mothers (n = 282)
      enrolled in a home visiting program. Home visitors (n = 56) were randomly
      assigned to perform safe sleep teaching and assessments during 3 visits: third
      trimester, 1 week old, and 2 months old, exclusively utilizing a specially
      designed children's book or brochures, and surveys incorporating the American
      Academy of Pediatrics' safe sleep recommendations. Outcomes were safe sleep
      knowledge, adherence, and usefulness of materials, controlling for maternal
      health literacy. RESULTS: Safe sleep knowledge increased across all time points
      with no overall group difference, though gains for sleep-evocative and general
      health items varied. Odds of bed sharing were higher and exclusive crib use lower
      for the brochure group (P < .05). Mothers and home visitors reported similar
      usefulness, though home visitors reported greater dialogue via the book and
      mothers in the book group reported more book sharing with their baby.
      CONCLUSIONS: While a specially designed children's book and brochures were
      equally effective conveying aggregate safe sleep knowledge in low-SES mothers,
      adherence to exclusive crib use and avoiding bed sharing were greater in the book
      group, attributable to enhanced dialogue, readability and emotional engagement.
      Children's books are a promising mode of anticipatory guidance, warranting
      further investigation.

PMID- 28450083
TI  - Improving the Quality of Home Health Care for Children With Medical Complexity.
AB  - OBJECTIVE: The objectives of this study are to describe the quality of home
      health care services for children with medical complexity, identify barriers to
      delivering optimal home health care, and discuss potential solutions to improve
      home health care delivery. METHODS: In this qualitative study, we conducted 20
      semistructured in-depth interviews with primary caregivers of children with
      medical complexity, and 4 focus groups with 18 home health nurses. During an
      iterative analysis process, we identified themes related to quality of home
      health care. RESULTS: There is substantial variability between home health nurses
      in the delivery of home health care to children. Lack of skills in nurses is
      common and has serious negative health consequences for children with medical
      complexity, including hospitalizations, emergency room visits, and need for
      medical procedures. Inadequate home health care also contributes to caregiver
      burden. A major barrier to delivering optimal home health care is the lack of
      training of home health nurses in pediatric care and technology use. Potential
      solutions for improving care include home health agencies training nurses in the
      care of children with medical complexity, support for nurses in clinical problem
      solving, and reimbursement for training nurses in pediatric home care. Caregiver
      level interventions includes preparation of caregivers about: providing medical
      care for their children at home and addressing problems with home health care
      services. CONCLUSIONS: There are problems in the quality of home health care
      delivered to children with medical complexity. Training nurses in the care of
      children with medical complexity and preparing caregivers about home care could
      improve home health care quality.

PMID- 28450085
TI  - Corrigendum to "Combined metabolic and transcriptional profiling identifies
      pentose phosphate pathway activation by HSP27 phosphorylation during cerebral
      ischemia" [Neuroscience 349 (2017) 1-16].

PMID- 28450084
TI  - Identification of a novel canine norovirus.
AB  - By screening a collection of fecal samples from young dogs from different
      European countries, noroviruses (NoVs) were found in 13/294 (4.4%) animals with
      signs of enteritis whilst they were not detected in healthy dogs (0/42). An
      informative portion of the genome (3.4kb at the 3' end) was generated for four
      NoV strains. In the capsid protein VP1 region, strains 63.15/2015/ITA and
      FD53/2007/ITA were genetically related to the canine GVI.2 strain
      C33/Viseu/2007/PRT (97.4-98.6% nt and 90.3-98.6% aa). Strain FD210/2007/ITA
      displayed the highest identity to the GVI.1 canine strain Bari/91/2007/ITA (88.0%
      nt and 95.0% aa). Strain 5010/2009/ITA displayed only 66.6-67.6% nt and 75.5
      81.6% aa identities to the GVI.1 canine strains FD210/2007/ITA and
      Bari/91/2007/ITA and the GVI feline strain M49-1/2012/JPN. Identity to the other
      canine/feline NoVs strains in the VP1 was lower than 67.6% nt and 62.7% aa. Based
      on the full-length VP1 amino acid sequence and the criteria proposed for
      distinction of NoV genotypes, the canine NoV 5010/2009/ITA could represent the
      prototype of a third GVI genotype, thus providing further evidence for the
      genetic heterogeneity of NoVs in carnivores.

PMID- 28450086
TI  - KRAS mutation testing on all non-malignant diagnosis of pancreatic endoscopic
      ultrasound-guided fine-needle aspiration biopsies improves diagnostic accuracy.
AB  - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the procedure of
      choice for the cytologic diagnosis of pancreatic masses. The specificity of EUS
      FNA approaches 100%, but the sensitivity is still low, and the high rate of
      indeterminate (atypical and suspicious) and false-negative results needs
      improvement. KRAS gene is frequently mutated in pancreatic ductal adenocarcinoma
      (PDAC) (up to 90%), and mutation analysis of KRAS has been proposed as diagnostic
      biomarker of PDAC. In most laboratories, KRAS mutation testing is performed by
      Sanger sequencing or real time-quantitative polymerase chain reaction (RT-qPCR),
      but these methods may give false-negative results in routine samples, mainly due
      to low cellularity. In order to increase the sensitivity of EUS-FNA, we propose a
      sequential approach for detecting KRAS mutations using mutant enriched-PCR (ME
      PCR, sensitivity up to 0.1%) in cytologically indeterminate and negative samples
      tested wild-type by RT-qPCR. EUS-FNA specimens from 107 patients with pancreatic
      masses (51 males, 56 females, mean age 67 years) were cytologically examined.
      According to the Papanicolaou Society of Cytopathology guidelines, 50 cases (47%)
      were classified malignant, 15 (14%) suspicious, 13 (12%) atypical and 10 (9%)
      negative for malignancy; 18 cases (17%) were non-diagnostic. The overall
      specificity and sensitivity of cytological examination were 100% and 61%,
      respectively, when only negative and positive cases were considered; when
      atypical and suspicious were added to positive cases, the sensitivity increased
      to 95.1% and the specificity decreased to 85.7%. In all the cases, DNA was
      extracted from the cell-block and KRAS mutations were investigated by RT-qPCR,
      followed by ME-PCR in non-amplifiable and negative cases. The overall sensitivity
      and specificity of KRAS mutation testing alone were 79.3% and 100%; when KRAS
      mutation testing was performed in indeterminate and negative cytology, the
      sensitivity increased to 90% with specificity to 100%. Our data indicate that
      conventional cytology from EUS-FNA samples is highly specific for the diagnosis
      of pancreatic cancer. Indeterminate and negative cases need to be screened for
      KRAS mutations; this two-step approach may greatly improve the diagnostic
      accuracy of this method.

PMID- 28450087
TI  - Validity and reliability of Ki-67 assessment in oestrogen receptor positive
      breast cancer.
AB  - Ki-67 is a prognostic and predictive biomarker in oestrogen receptor positive
      breast cancer. However, its measurement is not well standardised. This study
      compared the validity, intra- and inter-observer reproducibility and reporting
      time of five methods of Ki-67 assessment on tissue microarrays (TMA) and whole
      slides. Ki-67 labelling index (LI) was assessed on 71 breast carcinomas of no
      special type (NST), using five methods: manual counting (gold standard), unaided
      visual estimation, visual estimation aided by reference photographs, semi-manual
      digital image analysis (DIA) and fully automated DIA (Aperio platform). On TMA,
      semi-manual DIA demonstrated the closest agreement with the gold standard [intra
      class correlation coefficient (ICC)=0.99 (95% confidence interval 0.98-0.99)].
      All other methods also demonstrated close agreement [unaided estimation ICC=0.92
      (0.90-0.93), aided estimation ICC=0.93 (0.92-0.95), fully automated DIA ICC=0.97
      (0.96-0.97)]. On whole slides, both aided estimation and semi-manual DIA
      demonstrated excellent agreement with the gold standard [aided visual estimation
      ICC=0.91 (0.85-0.94), semi-manual DIA ICC=0.94 (0.89-0.96)]. Aided visual
      estimation significantly improved inter-observer reproducibility compared to
      unaided estimation [unaided ICC=0.87 (0.80-0.92); aided ICC=0.96 (0.93-0.97)] and
      corrected the underestimation bias seen in unaided estimation. Importantly,
      validity and reproducibility on whole slides were lower than on TMA for all
      methods of assessment, suggesting that field selection is an important source of
      variability in Ki-67 assessment. Values close to clinically used cut-off values
      therefore should be interpreted with caution.

PMID- 28450088
TI  - Non-BRCA familial breast cancer: review of reported pathology and molecular
      findings.
AB  - The majority of women evaluated for a clinical concern of possible hereditary
      breast cancer syndromes have no identified pathogenic variants in genes
      predisposing them to breast cancer. Non-BRCA1- or BRCA2-related familial breast
      cancer, also called 'BRCAX', thus comprises a sizeable proportion of familial
      breast cancer but it is poorly understood. In this study, we reviewed 14 studies
      on histopathology and molecular studies of BRCAX to determine if there were
      differences between 'sporadic' breast cancers and compared to cancers arising in
      women harbouring variants in known cancer predisposition genes. Across available
      literature, there was inconsistency on inclusion and exclusion criteria, reported
      parameters, and use of controls. Cohorts were small, and while several studies
      reported findings that appeared to distinguish the BRCAX cases from sporadic
      and/or gene-positive controls, no findings were reported in more than one study.
      To determine whether the BRCAX families might still contain important genetic
      subsets awaiting discovery will require prospective ascertainment of a large
      number of women with familial breast cancer who are screened for all currently
      established predisposition genes, whose tumours are assessed for multiple
      parameters in a uniform manner, and in which controls (BRCA1/2+ and non-familial
      'sporadic' cases) are collected from the same population.

PMID- 28450089
TI  - Gram negative resistance in community urine isolates.

PMID- 28450090
TI  - Malignant solitary fibrous tumour of the kidney with lymph node and liver
      metastases.

PMID- 28450091
TI  - PD-L1 and Notch1 expression in KSHV/HHV-8 and EBV associated germinotropic
      lymphoproliferative disorder: case report and review of the literature.

PMID- 28450092
TI  - Primary renal sclerosing epithelioid fibrosarcoma: a case report and review of
      the literature.

PMID- 28450093
TI  - Modified Creatinine Index and the Risk of Bone Fracture in Patients Undergoing
      Hemodialysis: The Q-Cohort Study.
AB  - BACKGROUND: Hemodialysis patients are at increased risk for bone fracture and
      sarcopenia. There is close interplay between skeletal muscle and bone. However,
      it is still unclear whether lower skeletal muscle mass increases the risk for
      bone fracture. STUDY DESIGN: Cross-sectional study and prospective longitudinal
      cohort study. SETTING & PARTICIPANTS: An independent cohort of 78 hemodialysis
      patients in the cross-sectional study and 3,030 prevalent patients undergoing
      maintenance hemodialysis prospectively followed up for 4 years. PREDICTOR:
      Skeletal muscle mass measured by bioelectrical impedance analysis (BIA) and
      modified creatinine index, an estimate of skeletal muscle mass based on age, sex,
      Kt/V for urea, and serum creatinine level. OUTCOMES: Bone fracture at any site.
      RESULTS: In the cross-sectional study, modified creatinine index was
      significantly correlated with skeletal muscle mass measured by BIA. During a
      median follow-up of 3.9 years, 140 patients had bone fracture. When patients were
      divided into sex-specific quartiles based on modified creatinine index, risk for
      bone fracture estimated by a Fine-Gray proportional subdistribution hazards model
      with all-cause death as a competing risk was significantly higher in the lower
      modified creatinine index quartiles (Q1 and Q2) compared to the highest modified
      creatinine index quartile (Q4) as the reference value in both sexes
      (multivariable-adjusted HRs for men were 7.81 [95% CI, 2.63-23.26], 5.48 [95% CI,
      2.08-14.40], 2.24 [95% CI, 0.72-7.00], and 1.00 [P for trend < 0.001], and for
      women were 4.44 [95% CI, 1.50-13.11], 2.33 [95% CI, 0.86-6.31], 1.96 [95% CI,
      0.82-4.65], and 1.00 [P for trend = 0.007] for Q1, Q2, Q3, and Q4, respectively).
      LIMITATIONS: One-time assessment of modified creatinine index; no data for
      residual kidney function and fracture sites and causes. CONCLUSIONS: Modified
      creatinine index was correlated with skeletal muscle mass measured by BIA. Lower
      modified creatinine index was associated with increased risk for bone fracture in
      male and female hemodialysis patients.

PMID- 28450094
TI  - Adverse effects of prenatal and early postnatal exposure to antiepileptic drugs:
      Validation from clinical and basic researches.
AB  - Epilepsy requires the long-term administration of antiepileptic drugs (AEDs), and
      thus, we must consider the effects of prenatal AED exposure on fetus when
      treating female patients of child bearing age. Large prospective clinical
      researches in humans have demonstrated the following: (1) prenatal exposure to
      valproic acid (VPA), carbamazepine, and phenobarbital increases the risk of
      congenital malformations in a dose-dependent manner and (2) prenatal exposure to
      VPA increases the risk of higher brain function impairments including
      intellectual disabilities and autistic spectrum disorders in the offspring.
      Furthermore, basic researches in animals have shown that prenatal exposure to
      specific AEDs causes microscopic structural abnormalities in the fetal brain.
      Specifically, prenatal exposure to VPA has been reported to inhibit the
      differentiation of neural progenitor cells during the early to middle phases of
      neuronogenesis, leading to increased number of projection neurons in the
      superficial layers of postnatal neocortices in mice. It is indispensable to
      prescribe AEDs that are associated with lower risk of congenital malformations
      and impairment of higher brain functions as well as to administer them at
      requisite minimum doses.

PMID- 28450095
TI  - Reply to: Early hypoperfusion on arterial spin labelling may be a diagnostic
      marker for acute encephalopathy with biphasic seizures and late reduced
      diffusion.

PMID- 28450096
TI  - Prediction of Pediatric Percutaneous Nephrolithotomy Outcomes Using Contemporary
      Scoring Systems.
AB  - PURPOSE: We evaluate the applicability of contemporary percutaneous
      nephrolithotomy scoring systems in pediatric patients and compare their
      predictive power regarding postoperative outcomes. MATERIALS AND METHODS: We
      retrospectively analyzed the records of 125 children who were diagnosed with
      renal calculi and underwent percutaneous nephrolithotomy between March 2011 and
      April 2016. Predictive scores, which consisted of Guy's Stone Score, S.T.O.N.E.
      (stone size, tract length, obstruction, number of involved calyces and
      essence/stone density) nephrolithometry and CROES (Clinical Research Office of
      the Endourological Society) nomogram, were calculated for all patients included
      in the study. Patient demographics, stone-free rate and complications were all
      analyzed and are reported. RESULTS: Median Guy's Stone Score was 2 (IQR 2 to 3)
      in patients with residual stones (group 1) and 2 (1 to 2) in those who were stone
      free (group 2). Median respective CROES nomogram scores were 215 (IQR 210 to 235)
      and 257 (240 to 264), and S.T.O.N.E. nephrolithometry scores were 8 (7 to 9) and
      5 (5 to 6, all p <0.0001). S.T.O.N.E. score demonstrated the greatest accuracy in
      predicting stone-free rate. Guy's Stone Score was significantly correlated with
      complications but the CROES and S.T.O.N.E. scores were not significantly
      correlated with complications. CONCLUSIONS: The scoring systems analyzed could be
      used to predict success of percutaneous nephrolithotomy in the pediatric setting.
      However, further studies are needed to formulate modifications for use in
      children. The main variables in the scoring systems, ie stone burden, tract
      length and case volume, were measured using records from adult patients. Besides
      these variables, the relatively small pelvicalyceal system and higher incidence
      of anatomical malformations in children could potentially affect percutaneous
      nephrolithotomy outcomes.

PMID- 28450097
TI  - Near-Infrared Vein Visualization in Index Finger Pollicization.
AB  - Near-infrared vein visualization devices allow for noninvasive identification of
      superficial veins. During index finger pollicization, preservation of the dorsal
      veins is important for protecting blood outflow from the digit. Near-infrared
      vein visualization devices can be used to identify the location of the dorsal
      veins prior to skin incision, allowing increased confidence during dissection. We
      describe the use of this device to identify veins during index finger
      pollicization.

PMID- 28450098
TI  - Crush Injuries of the Hand.
AB  - Crush injuries of the hand are a rare but devastating phenomenon, with
      historically poor outcomes. A compressive force, usually caused by a high-energy
      mechanism such as a motor vehicle or industrial accident, crushes and transiently
      increases the pressures within the hand. This force acts on the incompressible
      blood in the vasculature and leads to a dramatic rise in tissue pressures and
      damage to multiple tissue types, including bones, blood vessels, nerves, and soft
      tissues. A wide zone of injury results from a delayed inflammatory reaction
      involving the zone bordering the crushed cells, which may initially belie the
      severity of the injury. As such, these injuries go on to produce tremendous
      inflammation and swelling, potentially followed by compartment syndrome or other
      vascular damage, infection, neurological injury, and tissue necrosis. Crush
      injuries with minimal skin disruptions can be particularly challenging to
      accurately diagnose and manage. This paper provides a review of the initial
      evaluation of hand crush injuries as well as short- and long-term management
      strategies.

PMID- 28450099
TI  - Topographical Anatomy of the Distal Ulna Attachment of the Radioulnar Ligament.
AB  - PURPOSE: The deep component of the distal radioulnar ligament provides
      translational stability and rotational guidance to the forearm. However,
      controversy exists regarding the importance of this structure as well as the
      nature of its attachment to the distal ulna. We aimed to evaluate the topographic
      anatomy of the distal ulna attachment of both the superficial and the deep
      components of the radioulnar ligament and to assess the relationship between its
      internal and its external morphometry. METHODS: Thirteen human distal ulnae
      attached by ulnar part of the distal radioulnar ligament were scanned using micro
      computed tomography and reconstructed in 3 dimensions. In addition, the distal
      radioulnar ligaments were examined under polarized light microscopy to determine
      the histological characteristics of collagen contained within the ligaments.
      RESULTS: The deep limbs have broad marginal insertions at the fovea, whereas the
      superficial limbs have a circular and condensed insertion to the ulnar styloid.
      The center of the deep limb was separated from the base of the ulnar styloid by a
      mean of 2.0 +/- 0.76 mm, and this distance was positively correlated with the
      width of the ulnar styloid. The mean distance between the center of the ulnar
      head and the center of the fovea was 2.4 +/- 0.58 mm. The proportion of collagen
      type I was lower in the deep limb than in the superficial limb. CONCLUSIONS: This
      new observation of the footprint of the radioulnar ligament in the distal ulna
      indicates that the deep limb may serve as an internal capsular ligament of the
      distal radioulnar joint, whereas the superficial limb as the external ligament.
      CLINICAL RELEVANCE: Knowledge of the topographic anatomy of the radioulnar
      ligament's attachment to the distal ulna may provide a better understanding of
      distal radioulnar ligament-related pathologies.

PMID- 28450100
TI  - Effect of Radial Head Implant Shape on Radiocapitellar Joint Congruency.
AB  - PURPOSE: Radial head arthroplasty is indicated in displaced fractures in which
      comminution precludes successful internal fixation. Many types of radial head
      implants have been developed varying in material, methods of fixation, and
      degrees of modularity and geometry. The purpose of this study was to investigate
      the effect of radial head implant shape on radiocapitellar joint congruency.
      METHODS: Joint congruency was quantified in 7 cadaveric specimens employing a
      registration and inter-surface distance algorithm and 3-dimensional models
      obtained using computed tomography. Forearm rotation was simulated after computer
      guided implantation of an axisymmetric radial head, a population-based quasi
      anatomic radial head implant, and a reverse-engineered anatomic radial head
      implant. Inter-surface distances were measured to investigate the relative
      position of the radial head implant and displayed on 3-dimensional color-contour
      maps. Surface area was measured for inter-surface distances (1.5 mm) and compared
      for each radial head geometry. RESULTS: There were no statistical differences in
      the contact surface area between radial head implants during active or passive
      forearm rotation. The joint was more congruent (larger contact surface area)
      during active forearm rotation compared with passive forearm rotation.
      CONCLUSIONS: This study investigated the effect of implant geometry on the
      radiocapitellar joint contact mechanics by examining a commercially available
      radial head system (axisymmetric), a quasi-anatomic design, and an anatomic
      reverse-engineered radial head implant. We found no statistical differences in
      radiocapitellar joint contact mechanics as measured by 3-dimensional joint
      congruency in cadaveric specimens undergoing continuous simulated forearm
      rotation. CLINICAL RELEVANCE: The importance of choosing an implant that matches
      the general size of the native radial head is recognized, but the degree to which
      it is necessary to create an implant that replicates the native anatomy to
      restore elbow stability and prevent cartilage degenerative changes remains
      unclear. This study concluded that the geometry of the implant did not have a
      statistically significant effect on joint contact mechanics; therefore, future
      work is needed to examine additional factors related to implant design, such as
      material choice and implant positioning to investigate their influence on joint
      contact mechanics.

PMID- 28450101
TI  - Failed Suture Button Suspensionplasty of the Thumb Carpometacarpal Joint Salvaged
      Using Pyrocarbon Arthroplasty.
AB  - Carpometacarpal joint arthritis of the thumb is a common problem. Mini suture
      suspensionplasty has been reported as a successful treatment option. We describe
      a case of a ruptured suture button suspensionplasty that caused pain and thumb
      metacarpal subluxation. To our knowledge, this is the first reported mechanical
      failure of a suture suspensionplasty. Surgeons should be aware of this potential
      complication when using this device to treat thumb carpometacarpal arthritis
      surgically.

PMID- 28450102
TI  - An In Vitro Study of the Role of Implant Positioning on Ulnohumeral Articular
      Contact in Distal Humeral Hemiarthroplasty.
AB  - PURPOSE: To investigate the effect of implant positioning on ulnohumeral contact
      using patient-specific distal humeral (DH) implants. METHODS: Seven reverse
      engineered DH implants were manufactured based on computed tomography scans of
      their osseous geometry. Native ulnae were paired with corresponding native humeri
      and custom DH implants in a loading apparatus. The ulna was set at 90 degrees  of
      flexion and the humeral component (either native bone or reverse-engineered
      implant) was positioned from 5 degrees  varus to 5 degrees  valgus in 2.5 degrees
      increments under a 100-N compressive load. Contact with the ulna was measured
      with both the native distal humerus and the reverse-engineered DH implant at all
      varus-valgus (VV) angles, using a joint casting method. Contact patches were
      digitized and analyzed in 4 ulnar quadrants. Output variables were contact area
      and contact pattern. RESULTS: Mean contact area of the native articulation was
      significantly greater than with the distal humeral hemiarthroplasty (DHH)
      implants across all VV positions. Within the native condition, contact area did
      not significantly change owing to VV angulation. Within the DHH condition,
      contact area also did not significantly change owing to VV angulation.
      Conversely, in the DHH condition, contact pattern did significantly change.
      Medial ulnar contact pattern was significantly affected by VV angulation. Lateral
      ulnar contact was variably affected, but generally decreased as well.
      CONCLUSIONS: Ulnar contact patterns were changed as a result of VV implant
      positioning using reverse-engineered DH implants, most notably on the medial
      aspect of the joint. Implant positioning plays a crucial role in producing
      contact patterns more like those observed in the native joint. CLINICAL
      RELEVANCE: Recent clinical evidence reports nonsymmetrical ulnar wear after DHH.
      This work suggests that implant positioning is likely a contributing factor and
      that more exact implant positioning may lead to better clinical outcomes.

PMID- 28450104
TI  - Characterization of binding and quantification of human autoantibodies to
      PDGFRalpha using a biosensor-based approach.
AB  - Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective
      tissue. The variety and clinical relevance of autoantibodies in SSc patients have
      been extensively studied, eventually identifying agonistic autoantibodies
      targeting the platelet-derived growth factor receptor alpha (PDGFRalpha), and
      representing potential biomarkers for SSc. We used a resonant mirror biosensor to
      characterize the binding between surface-blocked PDGFRalpha and PDGFRalpha
      specific recombinant human monoclonal autoantibodies (mAbs) produced by SSc B
      cells, and detect/quantify serum autoimmune IgG with binding characteristics
      similar to the mAbs. Kinetic data showed a conformation-specific, high-affinity
      interaction between PDGFRalpha and mAbs, with equilibrium dissociation constants
      in the low-to-high nanomolar range. When applied to total serum IgG, the assay
      discriminated between SSc patients and healthy controls, and allowed the rapid
      quantification of autoimmune IgG in the sera of SSc patients, with anti
      PDGFRalpha IgG falling in the range 3.20-4.67 neq/L of SSc autoantibodies. The
      test was validated by comparison to direct and competitive anti-PDGFRalpha
      antibody ELISA. This biosensor assay showed higher sensibility with respect to
      ELISA, and other major advantages such as the specificity, rapidity, and
      reusability of the capturing surface, thus representing a feasible approach for
      the detection and quantification of high affinity, likely agonistic, SSc-specific
      anti-PDGFRalpha autoantibodies.

PMID- 28450105
TI  - Optimization of SNAP-25-derived peptide substrate for improved detection of
      botulinum A in the Endopep-MS assay.
AB  - Botulinum neurotoxins (BoNTs) are the most toxic proteins in nature.
      Endopeptidase-mass-spectrometry (Endopep-MS) is used as a specific and rapid in
      vitro assay to detect BoNTs. In this assay, immunocaptured toxin cleaves a
      serotype-specific-peptide-substrate, and the cleavage products are then detected
      by MS. Here we describe the design of a new peptide substrate for improved
      detection of BoNT type A (BoNT/A). Our strategy was based on reported BoNT/A-SNAP
      25 interactions integrated with analysis method efficiency considerations.
      Integration of the newly designed substrate led to a 10-fold increase in the
      assay sensitivity both in buffer and in clinically relevant samples.

PMID- 28450103
TI  - Regional variation in outcomes for lower extremity vascular disease in the
      Vascular Quality Initiative.
AB  - BACKGROUND: Increased focus has been placed on perioperative and long-term
      outcomes in the treatment of peripheral artery disease (PAD), both for purposes
      of quality improvement and for assessment of performance at a surgeon and
      institutional level. This study evaluates regional variation in outcomes after
      treatment for PAD within the Vascular Quality Initiative (VQI). By describing the
      variation in practice patterns and outcomes across regions, we hope that each
      regionally based quality group can select which areas are most important for them
      to focus on as they will have access to their regional data to compare. METHODS:
      We identified all patients in the VQI who had infrainguinal bypass or
      endovascular intervention from 2009 to 2014. We compared variation in
      perioperative and 1-year outcomes stratified by symptom status and
      revascularization type among the 16 regional groups of the VQI. We analyzed
      variation in perioperative end points using chi2 analysis, and 1-year end points
      were analyzed using Kaplan-Meier and life-table analysis. RESULTS: We identified
      15,338 bypass procedures for symptomatic PAD: 27% for claudication, 59% for
      chronic limb-threatening ischemia (CLI; 61% of these for tissue loss), and 14%
      for acute limb ischemia. We identified 33,925 endovascular procedures for
      symptomatic PAD: 42% for claudication, 48% for CLI (73% of these for tissue
      loss), and 10% for acute limb ischemia. Thirty-day mortality varied significantly
      after endovascular intervention for CLI (0.5%-3%; P < .001) but not for
      claudication (0.0%-0.5%, P = .77) or for bypass for claudication (0.0%-2.6%; P =
      .37) or CLI (0.0%-5.0%; P = .08). After bypass, rates of >2 units transfused red
      blood cells (claudication, 0.0%-13% [P < .001]; CLI, 6.9%-27% [P < .001]) varied
      significantly. In-hospital major amputation was variable after bypass for CLI
      (0.0%-4.3%; P = .004) but not for claudication (0.0%-0.6%; P = .98), as was
      postoperative myocardial infarction (claudication, 0.0%-4% [P = .36]; CLI, 0.8%
      6% [P = .001]). One-year survival varied significantly for endovascular
      interventions for claudication (92%-100%; P < .001), bypass for CLI (85%-94% [P <
      .001]), and endovascular interventions for CLI (77%-96%; P < .001) but not after
      bypass for claudication (95%-100%; P = .57). CONCLUSIONS: In this real-world
      comparison among VQI regions, we found significant variation in perioperative and
      1-year end points for patients with PAD undergoing bypass or endovascular
      intervention. This study highlights opportunities for quality improvement efforts
      to reduce variation and to improve outcomes.

PMID- 28450107
TI  - Autophagy regulates Endothelial-Mesenchymal transition by decreasing the
      phosphorylation level of Smad3.
AB  - Transforming growth factor-beta2 (TGF-beta2) induces Endothelial-Mesenchymal
      transition (EndoMT) and autophagy in a variety of cells. Previous studies have
      indicated that activation of autophagy might decrease TGF-beta2 induced EndoMT.
      However, the precise role remains unclear. In the present study, we found that
      TGF-beta2 could induce EndoMT and autophagy in human retinal microvascular
      endothelial cells (hRMECs). Activation of autophagy by Rapamycin or Trehalose
      could reduce the expression of Snail, demonstrating a role of autophagy in
      regulating Snail production both by transcriptional and post-transcriptional
      mechanism. Co-immunoprecipitation (CoIP) demonstrated that LC3 co
      immunoprecipitated with Smad3 and western blot showed that autophagy inducers,
      Rapamycin and Trehalose, could decrease the phosphorylation level of Smad3.
      Therefore, our results demonstrate that autophagy counteracts the EndoMT process
      triggered by TGF-beta2 by decreasing the phosphorylation level of Smad3.

PMID- 28450106
TI  - Detection of early endothelial damage in patients with Raynaud's phenomenon.
AB  - OBJECTIVES: Raynaud's phenomenon (RP) can be the first manifestation of systemic
      sclerosis (SSc) or other connective tissue diseases (CTDs), often preceding an
      overt disease by years. It is not known if markers of endothelial damage are
      detectable in those RP patients who subsequently develop a CTD. METHODS: We
      studied 82 RP patients at their first evaluation to correlate the levels of
      endothelial markers with the subsequent development of an overt disease 36months
      later. We measured plasma levels of tissue-type plasminogen activator (t-PA) and
      von Willebrand factor (vWF), two markers of endothelial damage, and interleukin-6
      (IL-6), a pro-inflammatory cytokine. Thirty sex- and age-matched healthy subjects
      (HS) served as controls. RESULTS: At baseline, 67 patients showed capillaroscopic
      normal pattern (CNP) and 15 patients, of which 11 were very early SSc, had
      capillaroscopic scleroderma pattern (CSP). Plasma levels of t-PA, vWF and IL-6
      were higher in patients with CNP (p=0.0001) than in HS and even much higher in
      patients with CSP (p=0.0001). In patients with CNP and RP of recent onset
      (<18months), vWF plasma levels were higher when autoantibodies were present
      (p=0.020). After 36months, among 48 RP patients with CNP who remained in follow
      up, 24 were diagnosed as primary and 24 as secondary RP. In secondary RP, basal
      levels of t-PA, IL-6 and particularly vWF were higher than in primary RP
      (p=0.005, p=0.004, p=0.0001 respectively) and HS (p=0.0001 for all). CONCLUSIONS:
      Our findings indicate that markers of endothelial damage are elevated in RP
      patients who subsequently develop SSc or other CTDs, even in the absence of
      capillaroscopic abnormalities.

PMID- 28450108
TI  - Disturbance of cell-size determination by forced overproduction of
      sulfoquinovosyl diacylglycerol in the cyanobacterium Synechococcus elongatus PCC
      7942.
AB  - Sulfoquinovosyl diacylglycerol (SQDG) is present in the membranes of
      cyanobacteria or their descendants, plastids at species-dependent levels. We
      investigated the physiological significance of the intrinsic SQDG content in the
      cyanobacterium Synechococcus elongatus PCC 7942, with the use of its mutant, in
      which the genes for SQDG synthesis, sqdB and sqdX, were overexpressed. The mutant
      showed a 1.3-fold higher content of SQDG (23.6 mol% relative to total cellular
      lipids, cf., 17.1 mol% in the control strain) with much less remarkable effects
      on the other lipid classes. Simultaneously observed were 1.6- to 1.9-fold
      enhanced mRNA levels for the genes responsible for the synthesis of the lipids
      other than SQDG, as if to compensate for the SQDG overproduction. Meanwhile, the
      mutant showed no injury to cell growth, however, cell length was increased (6.1
      +/- 2.3, cf., 3.8 +/- 0.8 MUm in the control strain). Accordingly with this, a
      wide range of genes responsible for cell division were 1.6-2.4-fold more highly
      expressed in the mutant. These results suggested that a regulatory mechanism for
      lipid homeostasis functions in the mutant, and that SQDG has to be kept from
      surpassing the intrinsic content in S. elongatus for repression of the abnormal
      expression of cell division-related genes and, inevitably, for normal cell
      division.

PMID- 28450109
TI  - T-type calcium channels, but not Cav3.2, in the peripheral sensory afferents are
      involved in acute itch in mice.
AB  - T-type calcium channels are prominently expressed in primary nociceptive fibers
      and well characterized in pain processes. Although itch and pain share many
      similarities including primary sensory fibers, the function of T-type calcium
      channels on acute itch has not been explored. We investigated whether T-type
      calcium channels expressed within primary sensory fibers of mouse skin,
      especially Cav3.2 subtype, involve in chloroquine-, endothelin-1- and histamine
      evoked acute itch using pharmacological, neuronal imaging and behavioral
      analyses. We found that pre-locally blocking three subtypes of T-type calcium
      channels in the peripheral afferents of skins, yielded an inhibition in acute
      itch or pain behaviors, while selectively blocking the Cav3.2 channel in the skin
      peripheral afferents only inhibited acute pain but not acute itch. These results
      suggest that T-type Cav3.1 or Cav3.3, but not Cav3.2 channel, have an important
      role in acute itch processing, and their distinctive roles in modulating acute
      itch are worthy of further investigation.

PMID- 28450110
TI  - A hydrocortisone derivative binds to GAPDH and reduces the toxicity of
      extracellular polyglutamine-containing aggregates.
AB  - Huntington's disease (HD) has been recently shown to have a horizontally
      transmitted, prion-like pathology. Thus, the migration of polyglutamine
      containing aggregates to acceptor cells is important for the progression of HD.
      These aggregates contain glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which
      increases their intracellular transport and their toxicity. Here, we show that
      RX624, a derivative of hydrocortisone that binds to GAPDH, prevents the formation
      of aggregates of GAPDH-polyglutamine excreted into the culture medium by PC-12
      rat cells expressing mutant huntingtin. RX624 was previously shown to be unable
      to penetrate cells and, thus, its principal therapeutic action might be the
      inhibition of polyglutamine-GAPDH complex aggregation in the extracellular
      matrix. The administration of RX624 to SH-SY5Y acceptor cells that incubated in
      conditioned medium from PC-12 cells expressing mutant huntingtin caused an
      approximately 20% increase in survival. This suggests that RX624 might be useful
      as a drug against polyglutamine pathologies, and that is could be administered
      exogenously without affecting target cell physiology. This protective effect was
      validated by the similar effect of an anti-GAPDH specific antibody.

PMID- 28450111
TI  - Molecular characterization of an AtPYL1-like protein, BrPYL1, as a putative ABA
      receptor in Brassica rapa.
AB  - Abscisic acid (ABA)-induced physiological changes are conserved in many land
      plants and underlie their responses to environmental stress and pathogens. The
      PYRABACTIN RESISTANCE1/PYR1-LIKE/REGULATORY COMPONENTS OF ABA RECEPTORS (PYLs)
      type receptors perceive the ABA signal and initiate signal transduction. Here, we
      show that the genome of Brassica rapa encodes 24 putative AtPYL-like proteins.
      The AtPYL-like proteins in Brassica rapa (BrPYLs) can also be classified into 3
      subclasses. We found that nearly all BrPYLs displayed high expression in at least
      one tissue. Overexpression of BrPYL1 conferred ABA hypersensitivity to
      Arabidopsis. Further, ABA activated the expression of an ABA-responsive reporter
      in Arabidopsis protoplasts expressing BrPYL1. Overall, these results suggest that
      BrPYL1 is a putative functional ABA receptor in Brassica rapa.

PMID- 28450112
TI  - NEDD8-activating enzyme inhibitor, MLN4924 (Pevonedistat) induces NOXA-dependent
      apoptosis through up-regulation of ATF-4.
AB  - It has been reported that MLN4924 can inhibit cell growth and metastasis in
      various kinds of cancer. We have reported that MLN4924 is able to inhibit
      angiogenesis through the induction of cell apoptosis both in vitro and in vivo
      models. Moreover, Neddylation inhibition using MLN4924 triggered the accumulation
      of pro-apoptotic protein NOXA in Human umbilical vein endothelial cells (HUVECs).
      However, the mechanism of MLN4924-induced NOXA up-regulation has not been
      addressed in HUVECs yet. In this study, we investigated how MLN4924 induced NOXA
      expression and cellular apoptosis in HUVECs treated with MLN4924 at indicated
      concentrations. MLN4924-induced apoptosis was evaluated by Annexin V-FITC/PI
      analysis and expression of genes associated with apoptosis was assessed by
      Quantitative RT-PCR and western blotting. As a result, MLN4924 triggered NOXA
      dependent apoptosis in a dose-dependent manner in HUVECs. Mechanistically,
      inactivation of Neddylation pathway caused up-regulation of activating
      transcription factor 4 (ATF-4), a substrate of Cullin-Ring E3 ubiquitin ligases
      (CRL). NOXA was subsequently transactivated by ATF-4 and further induced
      apoptosis. More importantly, knockdown of ATF-4 by siRNA significantly decreased
      NOXA expression and apoptotic induction in HUVECs. In summary, our study reveals
      a new mechanism underlying MLN4924-induced NOXA accumulation in HUVECs, which may
      help extend further study of MLN4924 for angiogenesis inhibition treatment.

PMID- 28450113
TI  - A CO-releasing molecule prevents annexin A2 down-regulation and associated
      disorders in LPS-administered rat lung.
AB  - To investigate septic lung injuries and the possible relief from injury by carbon
      monoxide (CO), rats were intraperitoneally (i.p.) administered water or the water
      soluble CO-releasing molecule CORM (30 mg/kg body weight), followed by the
      successive administration of PBS or lipopolysaccharide (LPS, 15 mg/kg body
      weight, 6 h). The results in four experimental groups (control, LPS, LPS + CORM,
      CORM, n = 3 or 4 in each groups) were examined. Histological examination revealed
      the intravascular aggregation of erythrocytes in the lungs of the LPS group, and
      serological analysis showed a significant increase in D-dimer in the LPS group.
      Both the aggregation and D-dimer increase were ameliorated in the LPS + CORM
      group, suggesting that LPS-induced DIC in the lung is ameliorated by CORM.
      Proteomic as well as immunoblot analyses revealed that the levels of annexin A2
      (AnxA2) were significantly decreased in the LPS group, but were at control levels
      in the LPS + CORM group. Concordant with the levels of AnxA2, the levels of both
      LC3 and collagen VI (COL VI) were decreased in the LPS group but not in the LPS +
      CORM group. Given the established roles of AnxA2 in fibrinolysis as well as
      intracellular vesicle trafficking, AnxA2 down-regulation should play an important
      role in the pathogenesis of septic lung injuries.

PMID- 28450114
TI  - The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium
      cells and retinal ganglion cells from UV radiation.
AB  - Excessive Ultra violet (UV) radiation induces injuries to retinal pigment
      epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal
      degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability
      transition pore (mPTP) opening mediates UV-induced cell death. In this study, we
      show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs
      from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it
      failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted
      shRNAs. Compound 19 almost blocked UV-induced p53-Cyp-D mitochondrial
      association, mPTP opening and subsequent cytochrome C release. Further studies
      showed that compound 19 inhibited UV-induced reactive oxygen species (ROS)
      production, lipid peroxidation and DNA damage. Together, compound 19 protects
      RPEs and RGCs from UV radiation, possibly via silencing Cyp-D-regulated intrinsic
      mitochondrial death pathway. Compound 19 could a lead compound for treating UV
      associated retinal degeneration diseases.

PMID- 28450115
TI  - Iron regulatory protein 2 in ovarian endometrial cysts.
AB  - Ovarian endometrial cysts cause some kinds of ovarian cancer, and iron is
      considered as one factor of carcinogenesis. In contrast, hypoxia is associated
      with progression, angiogenesis, metastasis, and resistance to therapy in cancer.
      We investigated hypoxia-induced perturbation of iron homeostasis in terms of
      labile iron, iron deposition, and iron regulatory protein (IRP) in ovarian
      endometrial cysts. Iron deposition, expression of IRPs, and a protein marker of
      hypoxia in human ovarian endometrial cysts were analyzed histologically. The
      concentration of free iron and the pO2 level of the cyst fluid of human ovarian
      cysts (n = 9) were measured. The expression of IRP2 under hypoxia was
      investigated in vitro by using Ishikawa cells as a model of endometrial cells.
      Iron deposition and the expression of IRP2 and Carbonic anhydrase 9 (CA9) were
      strong in endometrial stromal cells in the human ovarian endometrial cysts. The
      average concentration of free iron in the cyst fluid was 8.1 +/- 2.9 mg/L, and
      the pO2 was 22.4 +/- 5.2 mmHg. A cell-based study using Ishikawa cells revealed
      that IRP2 expression was decreased by an overload of Fe(II) under normoxia but
      remained unchanged under hypoxia even in the presence of excess Fe(II). An
      increase in the expression of IRP2 caused upregulation of intracellular iron as a
      result of the response to iron deficiency, whereas the protein was degraded under
      iron-rich conditions. We found that iron-rich regions existed in ovarian
      endometrial cysts concomitantly with the high level of IRP2 expression, which
      should generally be decomposed upon an overload of iron. We revealed that an
      insufficient level of oxygen in the cysts is the main factor for the unusual
      stabilization of IRP2 against iron-mediated degradation, which provides aberrant
      uptake of iron in ovarian endometrial stromal cells and can potentially lead to
      carcinogenesis.

PMID- 28450116
TI  - A characteristic chondroitin sulfate trisaccharide unit with a sulfated fucose
      branch exhibits neurite outgrowth-promoting activity: Novel biological roles of
      fucosylated chondroitin sulfates isolated from the sea cucumber Apostichopus
      japonicus.
AB  - Chondroitin sulfate (CS) is a class of sulfated glycosaminoglycan (GAG) chains
      that consist of repeating disaccharide unit composed of glucuronic acid (GlcA)
      and N-acetylgalactosamine (GalNAc). CS chains are found throughout the
      pericellular and extracellular spaces and contribute to the formation of
      functional microenvironments for numerous biological events. However, their
      structure-function relations remain to be fully characterized. Here, a
      fucosylated CS (FCS) was isolated from the body wall of the sea cucumber
      Apostichopus japonicus. Its promotional effects on neurite outgrowth were
      assessed by using isolated polysaccharides and the chemically synthesized FCS
      trisaccharide beta-D-GalNAc(4,6-O-disulfate) (1-4)[alpha-l-fucose (2,4-O
      disulfate) (1-3)]-beta-D-GlcA. FCS polysaccharides contained the E-type
      disaccharide unit GlcA-GalNAc(4,6-O-disulfate) as a CS major backbone structure
      and carried distinct sulfated fucose branches. Despite their relatively lower
      abundance of E unit, FCS polysaccharides exhibited neurite outgrowth-promoting
      activity comparable to squid cartilage-derived CS-E polysaccharides, which are
      characterized by their predominant E units, suggesting potential roles of the
      fucose branch in neurite outgrowth. Indeed, the chemically synthesized FCS
      trisaccharide was as effective as CS-E tetrasaccharide in stimulating neurite
      elongation in vitro. In conclusion, FCS trisaccharide units with 2,4-O-disulfated
      fucose branches may provide new insights into understanding the structure
      function relations of CS chains.

PMID- 28450117
TI  - TCF7L1 recruits CtBP and HDAC1 to repress DICKKOPF4 gene expression in human
      colorectal cancer cells.
AB  - The T-cell factor/Lymphoid enhancer factor (TCF/LEF; hereafter TCF) family of
      transcription factors are critical regulators of colorectal cancer (CRC) cell
      growth. Of the four TCF family members, TCF7L1 functions predominantly as a
      repressor of gene expression. Few studies have addressed the role of TCF7L1 in
      CRC and only a handful of target genes regulated by this repressor are known. By
      silencing TCF7L1 expression in HCT116 cells, we show that it promotes cell
      proliferation and tumorigenesis in vivo by driving cell cycle progression.
      Microarray analysis of transcripts differentially expressed in control and TCF7L1
      silenced CRC cells identified genes that control cell cycle kinetics and cancer
      pathways. Among these, expression of the Wnt antagonist DICKKOPF4 (DKK4) was
      upregulated when TCF7L1 levels were reduced. We found that TCF7L1 recruits the C
      terminal binding protein (CtBP) and histone deacetylase 1 (HDAC1) to the DKK4
      promoter to repress DKK4 gene expression. In the absence of TCF7L1, TCF7L2 and
      beta-catenin occupancy at the DKK4 promoter is stimulated and DKK4 expression is
      increased. These findings uncover a critical role for TCF7L1 in repressing DKK4
      gene expression to promote the oncogenic potential of CRCs.

PMID- 28450118
TI  - Importance of deubiquitinases in zebrafish craniofacial development.
AB  - Deconjugation of ubiquitin and/or ubiqutin-like modified substrates is essential
      to maintain a sufficient free ubiquitin within the cell. Deubiquitinases (DUBs)
      play a key role in the process. Besides, DUBs also play several important
      regulatory roles in cellular processes. However, our knowledge of their
      developmental roles are limited. The report here aims to study their potential
      roles in craniofacial development. Based on the previous genome-wide study in
      2009, we selected 36 DUBs to perform the morpholino (MO) knockdown in this study,
      followed by the Alcian blue cartilage staining at 5 days post-fertilization (dpf)
      larvae to investigate the facial development. Results classified the tested DUBs
      into three groups, in which 28% showed unchanged phenotype (Class 1); 22% showed
      mild changes on the branchial arches (Class 2A); 31% had malformation on
      branchial arches and ethmoid plate (Class 2B); and 19% had severe changes in most
      of the facial structures (Class 3). Lastly, we used uchl3 morphant as an example
      to show that our screening data could be useful for further functional studies.
      To summarize, we identified new craniofacial developmental role of 26 DUBs in the
      zebrafish.

PMID- 28450119
TI  - Role of the calcium sensing receptor in cardiomyocyte apoptosis via mitochondrial
      dynamics in compensatory hypertrophied myocardium of spontaneously hypertensive
      rat.
AB  - Calcium sensing receptor (CaSR) mediates pathological cardiac hypertrophy.
      Mitochondria maintain their function through fission and fusion and disruption of
      mitochondrial dynamic is linked to various cardiac diseases. This study examined
      how inhibition of CaSR by the inhibitor Calhex231 affected the mitochondrial
      dynamics in a hypertensive model in rats. Spontaneously hypertensive rats (SHRs)
      and Wistar Kyoto (WKY) rats were used in this study. Cardiac function and blood
      pressure was evaluated at the end of the study. SHRs showed increases in the
      ratio of heart weight to body weight and the levels of CaSR; all of these
      increases were suppressed by Calhex231. Additionally, Calhex231 treatment of SHRs
      changed the expression of proteins involved in mitochondrial dynamics. Our
      results demonstrated that CaSR activation induced cardiomyocyte apoptosis through
      the mitochondrial dynamics mediated apoptotic pathway in hypertensive hearts.

PMID- 28450120
TI  - HIV acquisition and transmission among men who have sex with men and women: What
      we know and how to prevent it.
AB  - Men who have sex with men and women (MSMW) compose a subset of men who have sex
      with men (MSM) and represent an estimated 35% of MSM. Research on the HIV risk
      behaviors of MSMW has largely focused on their behaviors in comparison to men who
      have sex with men only (MSMO). Results suggest that compared to MSMO, MSMW are
      less likely to have ever had an HIV test, are at greater risk of being unaware of
      their HIV infection and are less likely to have encountered HIV prevention
      activities or materials. Additional research is needed to provide a more
      comprehensive understanding of the unique sexual behaviors and lived experience
      of MSMW as a group in order to better inform HIV prevention efforts. The purpose
      of this paper is to summarize existing data and discuss strategies to reduce HIV
      acquisition and transmission among MSMW.

PMID- 28450121
TI  - Physical activity and telomere length in U.S. men and women: An NHANES
      investigation.
AB  - The principal objective was to determine the extent to which physical activity
      (PA) accounts for differences in leukocyte telomere length (LTL) in a large
      random sample of U.S. adults. Another purpose was to assess the extent to which
      multiple demographic and lifestyle covariates affect the relationship between PA
      and LTL. A total of 5823 adults from the National Health and Nutrition
      Examination Survey (NHANES 1999-2002) were studied cross-sectionally. Employing
      the quantitative polymerase chain reaction method, LTL was compared to standard
      reference DNA. PA was indexed using MET-minutes using self-reported frequency,
      intensity, and duration of participation in 62 physical activities. Covariates
      were controlled statistically. Telomeres were 15.6 base pairs shorter for each
      year of chronological age (F=723.2, P<0.0001). PA was inversely related to LTL
      after adjusting for all the covariates (F=8.3, P=0.0004). Telomere base pair
      differences between adults with High activity and those in the Sedentary, Low,
      and Moderate groups were 140, 137, and 111, respectively. Adults with High
      activity were estimated to have a biologic aging advantage of 9years (140 base
      pairs/15.6) over Sedentary adults. The difference in cell aging between those
      with High and Low activity was also significant, 8.8years, as was the difference
      between those with High and Moderate PA (7.1years). Overall, PA was significantly
      and meaningfully associated with telomere length in U.S. men and women.
      Evidently, adults who participate in high levels of PA tend to have longer
      telomeres, accounting for years of reduced cellular aging compared to their more
      sedentary counterparts.

PMID- 28450122
TI  - The stability of children's weight status over time, and the role of television,
      physical activity, and diet.
AB  - Weight-related behaviors such as sedentary activity, physical activity, and diet
      have been the focus of efforts to prevent and reduce the occurrence of obesity
      and overweight in children, but few longitudinal studies have examined the
      effects of weight-related behaviors on changes in weight status over time in
      children. This study examines the effects of weight-related behaviors on
      subsequent changes in weight during childhood. We used the Early Childhood
      Longitudinal Study Kindergarten Cohort (ECLS-K), a nationally representative
      prospective cohort of children in the United States. Data, including
      anthropometric measures, were collected six times across 1998-2007 (analytic
      sample=4938). We employed an autoregressive cross-lagged model in a structural
      equation model framework to assess the effects of behavioral factors -intake of
      fruit, vegetables, fast food and sugar-sweetened beverages, television viewing,
      and physical activity - on weight stability over time. BMI z-scores were highly
      stable throughout childhood: the standardized parameter estimates of BMI z-scores
      on subsequent-period BMI z-scores ranged from 0.79 to 0.86. BMI z-scores were
      least stable between Kindergarten and 1st grade but became highly stable between
      3rd and 5th grades. After accounting for prior weight, behavioral factors had
      little effect on subsequent weight. The most important behavioral factor was TV
      viewing in the 1st and 3rd grades: an additional hour of daily TV viewing was
      associated with 0.04 higher BMI z-score. It is important to prevent excessive
      weight gain early in childhood, as weight patterns are long-lasting; the most
      important behavioral factor may be limiting children's screen time.

PMID- 28450123
TI  - Behavioral lifestyle interventions for moderate and severe obesity: A systematic
      review.
AB  - Moderate and severe obesity (BMI >=35 kg/m2) affect 15% of US adults, with a
      projected increase over the next two decades. This study reviews evidence of
      behavioral lifestyle interventions for weight loss in this population. We
      searched PubMed, PsychInfo, CINAHL(r), and Scopus through February 2016 for
      experimental and quasi-experimental studies that tested a dietary and/or physical
      activity intervention with a behavioral modification component versus a
      comparator; and had >=six-month follow-up and a weight-related primary outcome.
      Twelve studies representing 1862 participants (mean BMI 37.5-48.3, mean age 30-54
      years) were included. Nine studies compared different behavioral interventions
      and three tested behavioral intervention(s) versus pharmacological or surgical
      treatments. Among the 25 behavioral interventions in the 12 studies, 18 reported
      percent of participants achieving clinically significant weight loss up to
      12months (32-97% achieving 5% or 3-70% achieving 10%). Three studies measured
      other cardiometabolic risk factors, but showed no significant risk reduction.
      Seven interventions with greater effectiveness (i.e., at least 31% achieving
      >=10% or 62% achieving >=5% weight loss up to one year) included multiple
      components (diet, physical activity, and behavioral strategies), long duration
      (e.g., one year), and/or intensive contacts (e.g., inpatient stays for clinic
      based interventions, weekly contacts for community-based ones). Evidence for the
      effectiveness of behavioral interventions versus pharmacological or surgical
      treatment was limited. Comprehensive and intensive behavioral interventions can
      result in clinically significant, albeit modest, weight loss in this obese
      subpopulation but may not result significant improvements in other
      cardiometabolic risk factors. More research on scalable and sustainable
      interventions is needed.

PMID- 28450124
TI  - Experiences of weight teasing in adolescence and weight-related outcomes in
      adulthood: A 15-year longitudinal study.
AB  - Weight-based teasing is common among youth, but little is known about its long
      term impact on health outcomes. We aimed to 1) identify whether weight-based
      teasing in adolescence predicts adverse eating and weight-related outcomes
      15years later; and 2) determine whether teasing source (peers or family) affects
      these outcomes. Data were collected from Project EAT-IV (Eating and Activity in
      Teens and Young Adults) (N=1830), a longitudinal cohort study that followed a
      diverse sample of adolescents from 1999 (baseline) to 2015 (follow-up). Weight
      based teasing at baseline was examined as a predictor of weight status, binge
      eating, dieting, eating as a coping strategy, unhealthy weight control, and body
      image at 15-year follow-up. After adjusting for demographic covariates and
      baseline body mass index (BMI), weight-based teasing in adolescence predicted
      higher BMI and obesity 15years later. For women, these longitudinal associations
      occurred across peer and family-based teasing sources, but for men, only peer
      based teasing predicted higher BMI. The same pattern emerged for adverse eating
      outcomes; weight-based teasing from peers and family during adolescence predicted
      binge eating, unhealthy weight control, eating to cope, poor body image, and
      recent dieting in women 15years later. For men, teasing had fewer longitudinal
      associations. Taken together, this study shows that weight-based teasing in
      adolescence predicts obesity and adverse eating behaviors well into adulthood,
      with differences across gender and teasing source. Findings underscore the
      importance of addressing weight-based teasing in educational and health
      initiatives, and including the family environment as a target of anti-bullying
      intervention, especially for girls.

PMID- 28450125
TI  - The impact of household and community cash transfers on children's food
      consumption in Indonesia.
AB  - The current state of child nutrition is critical. About 5.9 million children
      under the age of five still died worldwide with nearly half are attributable to
      undernutrition. One explanation is inequality in children's food consumption. One
      strategy to address inequality among the poor is conditional cash transfers
      (CCTs). Taking advantage of the two large clustered-randomized trials in
      Indonesia from 2007 to 2009, this paper provides evidence on the impact of
      household cash transfer (PKH) and community cash transfer (Generasi) on child's
      food consumption. The sample sizes are 14,000 households for PKH and 12,000
      households for Generasi. After two years of implementation, difference-in
      differences (DID) analyses show that both cash transfers lead to significant
      increases in food consumption particularly for protein-rich items. The programs
      significantly increase the consumption of milk and fish by up to 19% and 14% for
      PKH and Generasi, respectively. Both programs significantly reduce some measures
      of severe malnutrition. PKH significantly reduces the probability of wasting and
      severe wasting by 33% and 41% and Generasi significantly reduces the probability
      of being severely underweight by 47%. This underscores the potential of household
      and community cash transfers to fight undernutrition among the poor.

PMID- 28450127
TI  - Carcinogenicity of consumption of red meat and processed meat: A review of
      scientific news since the IARC decision.
AB  - In October 2015, the International Agency for Research on Cancer (IARC) issued a
      press release on the results of the evaluation of the carcinogenicity of red and
      processed meat. Based on the accumulated scientific literature, the consumption
      of red meat was classified as "probably carcinogenic to humans" and processed
      meat as "carcinogenic to humans". Given the importance of this topic, this review
      was aimed at revising the current state-of-the-art on the carcinogenicity of red
      and processed meat, some time after the IARC decision. Some new epidemiological
      studies and new reviews clearly supporting the IARC decision have been published
      during these months. However, a number of gaps still exist. It is basic to
      establish the mechanisms leading to the increased risk of colorectal cancer (CRC)
      and other cancers arising from red and processed meat consumption. Another
      important pending issue is to establish the role of known/suspected carcinogens
      contained in uncooked or unprocessed meats, as well as the influence of cooking.
      Finally, it would be highly recommended to conduct new epidemiological studies to
      elucidate whether the consumption of white meat, such as pork and/or poultry, are
      -positively or inversely-associated with an increased risk of CRC and other types
      of cancer.

PMID- 28450126
TI  - Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates
      NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells.
AB  - Silybum marianum (milk thistle) is a medicinal plant used for the treatment of
      various liver disorders. This study examined whether the main flavonolignans from
      S. marianum (i.e. silybin, silychristin, silydianin) and their 2,3-dehydro
      derivatives (i.e. 2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3
      dehydrosilydianin) activate the Nrf2 pathway, which regulates the expression of
      genes encoding many cytoprotective enzymes, including NAD(P)H:quinone
      oxidoreductase 1 (NQO1). After 48h of exposure, 2,3-dehydrosilydianin at
      concentrations of 25MUM and higher significantly elevated the activity of NQO1 in
      murine hepatoma Hepa1c1c7 cells. In contrast, other tested compounds at non
      cytotoxic concentrations had a mild or negligible effect on the NQO1 activity.
      Using a luciferase reporter assay, 2,3-dehydrosilydianin was found to
      significantly activate transcription via the antioxidant response element in
      stably transfected human AREc32 reporter cells. Moreover, 2,3-dehydrosilydianin
      caused the accumulation of Nrf2 and significantly induced the expression of the
      Nqo1 gene at both the mRNA and protein levels in Hepa1c1c7 cells. We found that
      2,3-dehydrosilydianin also increased to some extent the expression of other Nrf2
      target genes, namely of the heme oxygenase-1 gene (Hmox1) and the glutamate
      cysteine ligase modifier subunit gene (Gclm). We conclude that 2,3
      dehydrosilydianin activates Nrf2 and induces Nrf2-mediated gene expression in
      Hepa1c1c7 cells.

PMID- 28450128
TI  - Protective effects of lichen metabolites evernic and usnic acids against redox
      impairment-mediated cytotoxicity in central nervous system-like cells.
AB  - Lichens species produce unique secondary metabolites that attract increasing
      pharmacological interest, including their redox modulatory activities. Current
      work evaluated for the first time the in vitro cytoprotective properties, based
      on the antioxidant activities, of the Parmeliaceae lichens Evernia prunastri and
      Usnea ghattensis and the mechanism of action of their major phenolic
      constituents: the evernic and usnic acids, respectively. In two models of central
      nervous system-like cells (U373-MG and SH-SY5Y cell lines), exogenous H2O2
      induced oxidative stress-mediated cytotoxicity. We first assessed their radical
      scavenging capacities (ORAC and DPPH tests) and the phenolic content of the
      extracts. At the optimal concentrations, pretreatments with evernic acid
      displayed significant protection against H2O2-induced cytotoxic damage in both
      models. It reversed the alterations in oxidative stress markers (including ROS
      generation, glutathione system and lipid peroxidation levels) and cellular
      apoptosis (caspase-3 activity). Such effects were in part mediated by a notable
      enhancement of the expression of intracellular phase-II antioxidant enzymes; a
      plausible involvement of the Nrf2 cytoprotective pathway is suggested. Usnic acid
      exerted similar effects, to some extent more moderate. Results suggest that
      lichen polyketides evernic and usnic acids merit further research as promising
      antioxidant candidates in the therapy of oxidative stress-related diseases,
      including the neurodegenerative disorders.

PMID- 28450129
TI  - Antioxidant capacity of trans-resveratrol dietary supplements alone or combined
      with the mycotoxin beauvericin.
AB  - Trans-resveratrol (trans-RSV) is a polyphenol with multiples biological
      properties, such as anti-inflammatory, antioxidant, anti-aging, anti-diabetic,
      and antiplatelet. It occurs naturally in grapes and derivate, peanuts and
      berries. Beauvericin (BEA) is a mycotoxin present in cereals that produces
      cytotoxicity, intracellular reactive oxygen species and lipid peroxidation. The
      general objective of this research was to evaluate whether trans-RSV could be
      used as a good polyphenol against damages produced by BEA. Because trans-RSV can
      be ingested through dietary supplements, to reach this goal, the following
      specific objectives were proposed: to determine a) the trans-RSV content in
      different polyphenol dietary supplements by capillary electrophoresis, b) the
      antioxidant capacity of the trans-RSV in polyphenol supplements, and c) the
      influence of BEA in the antioxidant capacity of trans-RSV when they are in
      combination by photochemioluminiscence assay. The results obtained in this study
      showed that all polyphenol dietary supplements present higher RSV content that
      the content of the label. The polyphenol supplements present antioxidant
      capacity. And the combination of trans-RSV and BEA did not affect the antioxidant
      capacity of trans-RSV. Thus, RSV could contribute to decrease oxidant effects
      produced by BEA.

PMID- 28450130
TI  - From Gene to Function: Cell-Free Electrophysiological and Optical Analysis of Ion
      Pumps in Nanodiscs.
AB  - Nanodiscs that hold a lipid bilayer surrounded by a boundary of scaffold proteins
      have emerged as a powerful tool for membrane protein solubilization and analysis.
      By combining nanodiscs and cell-free expression technologies, even completely
      detergent-free membrane protein characterization protocols can be designed.
      Nanodiscs are compatible with various techniques, and due to their bilayer
      environment and increased stability, they are often superior to detergent
      micelles or liposomes for membrane protein solubilization. However, transport
      assays in nanodiscs have not been conducted so far, due to limitations of the two
      dimensional nature of nanodisc membranes that offers no compartmentalization.
      Here, we study Krokinobacter eikastus rhodopsin-2 (KR2), a microbial light-driven
      sodium or proton pump, with noncovalent mass-spectrometric, electrophysiological,
      and flash photolysis measurements after its cotranslational insertion into
      nanodiscs. We demonstrate the feasibility of adsorbing nanodiscs containing KR2
      to an artificial bilayer. This allows us to record light-induced capacitive
      currents that reflect KR2's ion transport activity. The solid-supported membrane
      assay with nanodisc samples provides reliable control over the ionic condition
      and information of the relative ion activity of this promiscuous pump. Our
      strategy is complemented with flash photolysis data, where the lifetimes of
      different photointermediates were determined at different ionic conditions. The
      advantage of using identical samples to three complementary approaches allows for
      a comprehensive comparability. The cell-free synthesis in combination with
      nanodiscs provides a defined hydrophobic lipid environment minimizing the
      detergent dependence often seen in assays with membrane proteins. KR2 is a
      promising tool for optogenetics, thus directed engineering to modify ion
      selectivity can be highly beneficial. Our approach, using the fast generation of
      functional ion pumps incorporated into nanodiscs and their subsequent analysis by
      several biophysical techniques, can serve as a versatile screening and
      engineering platform. This may open new avenues for the study of ion pumps and
      similar electrogenic targets.

PMID- 28450131
TI  - Cerebral microbleeds, cognitive impairment, and MRI in patients with diabetes
      mellitus.
AB  - Cerebral microbleeds (CMBs), a typical imaging manifestation marker of sporadic
      cerebral small vessel disease, play a critical role in vascular cognitive
      impairment, which is often accompanied by diabetes mellitus (DM). Hence, CMBs
      may, in part, be responsible for the occurrence and development of cognitive
      impairment in patients with diabetes. Novel magnetic resonance imaging (MRI)
      sequences, such as susceptibility-weighted imaging and T2*-weighted gradient
      echo, have the capability of noninvasively revealing CMBs in the brain. Moreover,
      a correlation between CMBs and cognitive impairment in patients with diabetes has
      been suggested in applications of functional MRI (fMRI). Since pathological
      changes in the brain occur prior to observable decline in cognitive function,
      neuroimaging may help predict the progression of cognitive impairment in diabetic
      patients. In this article, we review the detection of CMBs using MRI in diabetic
      patients exhibiting cognitive impairment. Future studies should emphasize the
      development and establishment of a novel MRI protocol, including fMRI, for
      diabetic patients with cognitive impairment to detect CMBs. A reliable MRI
      protocol would also be helpful in understanding the pathological mechanisms of
      cognitive impairment in this important patient population.

PMID- 28450132
TI  - A novel splicing mutation in GALT gene causing Galactosemia in Ecuadorian family.
AB  - Classic Galactosemia (OMIM 230400) is an autosomal recessive disorder of
      galactose metabolism caused by mutations in the galactose-1-phosphate uridyl
      transferase (GALT) gene. This disease caused by the inability to metabolize
      galactose is potentially life-threatening but its pathophysiology has not been
      clearly defined. GALT gene presents high allelic heterogeneity and around 336
      variations have been identified. Here, we report the case of a patient with
      Classic Galactosemia who was detected during a neonatal screening in Ecuador.
      Molecular study revealed a mutation in GALT gene intron 1, c.82+3A>G in
      homozygous condition, this mutation has not been previously reported. This gene
      variation was not found in any of the 119 healthy Ecuadorian individuals used as
      control. Furthermore, the mutation was the only alteration detected in the
      propositus's GALT after sequencing all exons and introns of this gene. In silico
      modeling predicted that the mutation was pathogenic.

PMID- 28450133
TI  - Corticosteroid modulation and testosterone changes during alcohol intoxication
      affects voluntary alcohol drinking.
AB  - A number of studies have shown that stress and an activated hypothalamic
      pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol
      drinking. Recently, associations have been found between activated HPA and
      hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non
      preferring ANA, F2 (crossbred second generation from original AA and ANA), and
      Wistar rats. The aim of the present study has been to determine the role of
      corticosterone and alcohol-related testosterone-effects in subsequent alcohol
      drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four
      substudies presenting new analyses of existing data, by which correlations
      between basal corticosterone levels, changes in testosterone levels during
      alcohol intoxications and subsequent voluntary alcohol consumption are
      investigated. The results displayed positive correlations between basal
      corticosterone levels and subsequent alcohol-mediated testosterone elevations,
      which was positively associated with voluntary alcohol consumption. The results
      also showed a negative correlation between basal corticosterone levels and
      alcohol-mediated testosterone decreases, which was negatively associated with
      alcohol consumption. In conclusion, the present study displays novel results,
      according to which the HPA axis, one hand, relates to testosterone elevation
      (potentially causing and/or strengthening reinforcement) during alcohol
      intoxication, which in turn may relate to higher voluntary alcohol consumption
      (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated
      testosterone decrease (causing testosterone reduction and disinforcement) and low
      alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results
      showed that alcohol-mediated testosterone changes may also, independently of the
      HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of
      genetic factors. Thus, the role of the HPA-axis may be more related to
      situational stress than to intrinsic factors. In further studies, it should be
      investigated, whether the present results also apply to stress and human alcohol
      drinking.

PMID- 28450134
TI  - Variability in Integrated Cardiothoracic Training Program Curriculum.
AB  - BACKGROUND: Development of curricula that appropriately progress a resident from
      medical school graduate to fully trained cardiothoracic surgeon is a key
      challenge for integrated cardiothoracic training programs. This study examined
      variability and perceived challenges in integrated curricula. METHODS: Responses
      to the 2016 TSDA/TSRA survey that accompanies the annual in-training exam taken
      by current cardiothoracic surgery residents were analyzed. Standard statistical
      methods were utilized to examine trends in participant responses. RESULTS:
      General surgery experience decreased with post-graduate year, whereas cardiac
      operative experience increased. Rotations in a wide variety of adjunct fields
      were common. The majority (87%) of respondents reported had dedicated
      cardiothoracic intensive care unit (ICU) rotations, and surgical ICU and cardiac
      care unit rotations were less common (68% and 42%, respectively). The most common
      surgical subspecialty rotations were vascular (94%) and acute care surgery (88%),
      with a wide range of clinical exposure (ie, 3-44 weeks for vascular).
      Importantly, 52% felt competition with general surgery residents for experience
      and 22.5% of general surgery rotations were at hospitals without general surgery
      residents. Perceived challenges included optimization of rotations (78%), faculty
      allowing residents to perform case components (60%), faculty teaching in the
      operating room (29%), and improving surgical experience on general surgery
      rotations (19%). CONCLUSIONS: Significant variation exists in integrated
      cardiothoracic surgery curricula. Optimization of rotations, access to surgical
      experience, and integration with general surgery appear to be the most
      significant perceived challenges. These data suggest that optimization of early
      clinical and surgical experience within institutions could improve trainee
      preparedness for senior cardiothoracic surgery training.

PMID- 28450135
TI  - Transcatheter Aortic Valve Replacement Outcomes in Nonagenarians Stratified by
      Transfemoral and Transapical Approach.
AB  - BACKGROUND: Survival and other outcomes of nonagenarians undergoing transcatheter
      aortic valve replacement (TAVR) in the Medicare population are unclear. METHODS:
      Patients aged 65 years and older who underwent TAVR from November 2011 through
      2013 were considered for inclusion. RESULTS: The study consisted of 18,283
      patients and 19.3% were aged 90 years or older. Compared with patients younger
      than 90 years, patients 90 years or older were less likely to have a number of
      comorbidities, including previous myocardial infarction (17.5% versus 21.8%),
      previous coronary artery bypass grafting (20.0% versus 35.0%), and chronic
      obstructive pulmonary disease (25.4% versus 39.0%) among others. The 30-day and 1
      year mortality rates were 8.4% versus 5.9% (p = 0.0001) and 25.4% versus 21.5% (p
      = 0.0001) in the older and younger groups, respectively (odds ratio [OR] 1.47,
      95% confidence interval [CI]: 1.28 to 1.70, p = 0.0001). Patients 90 years and
      older were more likely to undergo pacemaker insertion (11.1% versus 8.3%, p =
      0.0001). Among nonagenarians, compared with the transapical group, patients
      undergoing transfemoral TAVR had lower 30-day (7.2% versus 13.6%, p = 0.0001) and
      1-year (23.8% versus 31.6%, p = 0.0001) mortality rates, were more likely to be
      discharged home (54.4% versus 34.1%, p = 0.0001), and had lower 30-day
      readmission rates (23.8% versus 31.8%, p = 0.0001). After adjustment for patient
      characteristics, transapical TAVR was an independent predictor of 30-day
      mortality rate (OR 1.94, 95% CI: 1.48 to 2.56, p = 0.0001) and readmission (OR
      1.46, 95% CI: 1.19 to 1.80, p = 0.0003). CONCLUSIONS: In patients undergoing
      TAVR, although 30-day and 1-year mortality rates were slightly worse for
      nonagenarians than their younger counterparts, long-term survival was still
      encouraging, with 75% of nonagenarians living to 1 year. Transapical TAVR was
      associated with worse outcomes in nonagenarians.

PMID- 28450136
TI  - The Use of Topical Hemostatic Agents in Cardiothoracic Surgery.
AB  - Topical hemostatic agents are used in conjunction with conventional procedures to
      reduce blood loss. They are often used in cardiothoracic surgery, which is
      particularly prone to bleeding risks. Variation in their use exists because
      detailed policy and practice guidelines reflecting the current medical evidence
      have not been developed to promote best surgical practice in this setting. To
      address this need, the Society for the Advancement of Blood Management convened
      an International Hemostatic Expert Panel. This article reviews the available
      literature and sets out evidence-based recommendations for the use of topical
      hemostatic agents in cardiothoracic surgery.

PMID- 28450137
TI  - Impact of Transcatheter Technology on Surgical Aortic Valve Replacement Volume,
      Outcomes, and Cost.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) represents a disruptive
      technology that is rapidly expanding in use. We evaluated the effect on surgical
      aortic valve replacement (SAVR) patient selection, outcomes, volume, and cost.
      METHODS: A total of 11,565 patients who underwent SAVR, with or without coronary
      artery bypass grafting (2002 to 2015), were evaluated from the Virginia Cardiac
      Services Quality Initiative database. Patients were stratified by surgical era:
      pre-TAVR era (2002 to 2008, n = 5,113), early-TAVR era (2009 to 2011, n = 2,709),
      and commercial-TAVR era (2012 to 2015, n = 3,743). Patient characteristics,
      outcomes, and resource utilization were analyzed by univariate analyses. RESULTS:
      Throughout the study period, statewide SAVR volumes increased with median volumes
      of pre-TAVR: 722 cases/year, early-TAVR: 892 cases/year, and commercial-TAVR: 940
      cases/year (p = 0.005). Implementation of TAVR was associated with declining
      Society of Thoracic Surgeons predicted risk of mortality among SAVR patients
      (3.7%, 2.6%, and 2.4%; p < 0.0001), despite increasing rates of comorbid disease.
      The mortality rate was lowest in the current commercial-TAVR era (3.9%, 4.3%, and
      3.2%; p = 0.05), and major morbidity decreased throughout the time period (21.2%,
      20.5%, and 15.2%; p < 0.0001). The lowest observed-to-expected ratios for both
      occurred in the commercial-TAVR era (0.9 and 0.9, respectively). Resource
      utilization increased generally, including total cost increases from $42,835 to
      $51,923 to $54,710 (p < 0.0001). CONCLUSIONS: At present, SAVR volumes have not
      been affected by the introduction of TAVR. The outcomes for SAVR continue to
      improve, potentially due to availability of transcatheter options for high-risk
      patients. Despite rising costs for SAVR, open approaches still provide a
      significant cost advantage over TAVR.

PMID- 28450138
TI  - Test-retest reliability of prefrontal transcranial Direct Current Stimulation
      (tDCS) effects on functional MRI connectivity in healthy subjects.
AB  - Transcranial Direct Current Stimulation (tDCS) of the prefrontal cortex (PFC) can
      be used for probing functional brain connectivity and meets general interest as
      novel therapeutic intervention in psychiatric and neurological disorders. Along
      with a more extensive use, it is important to understand the interplay between
      neural systems and stimulation protocols requiring basic methodological work.
      Here, we examined the test-retest (TRT) characteristics of tDCS-induced
      modulations in resting-state functional-connectivity MRI (RS fcMRI). Twenty
      healthy subjects received 20minutes of either active or sham tDCS of the
      dorsolateral PFC (2mA, anode over F3 and cathode over F4, international 10-20
      system), preceded and ensued by a RS fcMRI (10minutes each). All subject
      underwent three tDCS sessions with one-week intervals in between. Effects of tDCS
      on RS fcMRI were determined at an individual as well as at a group level using
      both ROI-based and independent-component analyses (ICA). To evaluate the TRT
      reliability of individual active-tDCS and sham effects on RS fcMRI, voxel-wise
      intra-class correlation coefficients (ICC) of post-tDCS maps between testing
      sessions were calculated. For both approaches, results revealed low reliability
      of RS fcMRI after active tDCS (ICC(2,1) = -0.09 - 0.16). Reliability of RS fcMRI
      (baselines only) was low to moderate for ROI-derived (ICC(2,1) = 0.13 - 0.50) and
      low for ICA-derived connectivity (ICC(2,1) = 0.19 - 0.34). Thus, for ROI-based
      analyses, the distribution of voxel-wise ICC was shifted to lower TRT reliability
      after active, but not after sham tDCS, for which the distribution was similar to
      baseline. The intra-individual variation observed here resembles variability of
      tDCS effects in motor regions and may be one reason why in this study robust tDCS
      effects at a group level were missing. The data can be used for appropriately
      designing large scale studies investigating methodological issues such as sources
      of variability and localisation of tDCS effects.

PMID- 28450139
TI  - 3D fully convolutional networks for subcortical segmentation in MRI: A large
      scale study.
AB  - This study investigates a 3D and fully convolutional neural network (CNN) for
      subcortical brain structure segmentation in MRI. 3D CNN architectures have been
      generally avoided due to their computational and memory requirements during
      inference. We address the problem via small kernels, allowing deeper
      architectures. We further model both local and global context by embedding
      intermediate-layer outputs in the final prediction, which encourages consistency
      between features extracted at different scales and embeds fine-grained
      information directly in the segmentation process. Our model is efficiently
      trained end-to-end on a graphics processing unit (GPU), in a single stage,
      exploiting the dense inference capabilities of fully CNNs. We performed
      comprehensive experiments over two publicly available datasets. First, we
      demonstrate a state-of-the-art performance on the ISBR dataset. Then, we report a
      large-scale multi-site evaluation over 1112 unregistered subject datasets
      acquired from 17 different sites (ABIDE dataset), with ages ranging from 7 to 64
      years, showing that our method is robust to various acquisition protocols,
      demographics and clinical factors. Our method yielded segmentations that are
      highly consistent with a standard atlas-based approach, while running in a
      fraction of the time needed by atlas-based methods and avoiding
      registration/normalization steps. This makes it convenient for massive multi-site
      neuroanatomical imaging studies. To the best of our knowledge, our work is the
      first to study subcortical structure segmentation on such large-scale and
      heterogeneous data.

PMID- 28450140
TI  - Effect of confounding variables on hemodynamic response function estimation using
      averaging and deconvolution analysis: An event-related NIRS study.
AB  - Slow and rapid event-related designs are used in fMRI and functional near
      infrared spectroscopy (fNIRS) experiments to temporally characterize the brain
      hemodynamic response to discrete events. Conventional averaging (CA) and the
      deconvolution method (DM) are the two techniques commonly used to estimate the
      Hemodynamic Response Function (HRF) profile in event-related designs. In this
      study, we conducted a series of simulations using synthetic and real NIRS data to
      examine the effect of the main confounding factors, including event sequence
      timing parameters, different types of noise, signal-to-noise ratio (SNR),
      temporal autocorrelation and temporal filtering on the performance of these
      techniques in slow and rapid event-related designs. We also compared systematic
      errors in the estimates of the fitted HRF amplitude, latency and duration for
      both techniques. We further compared the performance of deconvolution methods
      based on Finite Impulse Response (FIR) basis functions and gamma basis sets. Our
      results demonstrate that DM was much less sensitive to confounding factors than
      CA. Event timing was the main parameter largely affecting the accuracy of CA. In
      slow event-related designs, deconvolution methods provided similar results to
      those obtained by CA. In rapid event-related designs, our results showed that DM
      outperformed CA for all SNR, especially above -5 dB regardless of the event
      sequence timing and the dynamics of background NIRS activity. Our results also
      show that periodic low-frequency systemic hemodynamic fluctuations as well as
      phase-locked noise can markedly obscure hemodynamic evoked responses. Temporal
      autocorrelation also affected the performance of both techniques by inducing
      distortions in the time profile of the estimated hemodynamic response with
      inflated t-statistics, especially at low SNRs. We also found that high-pass
      temporal filtering could substantially affect the performance of both techniques
      by removing the low-frequency components of HRF profiles. Our results emphasize
      the importance of characterization of event timing, background noise and SNR when
      estimating HRF profiles using CA and DM in event-related designs.

PMID- 28450141
TI  - A shared representation of order between encoding and recognition in visual short
      term memory.
AB  - Many complex tasks require people to bind individual events into a sequence that
      can be held in short term memory (STM). For this purpose information about the
      order of the individual events in the sequence needs to be maintained in an
      active and accessible form in STM over a period of few seconds. Here we
      investigated how the temporal order information is shared between the
      presentation and response phases of an STM task. We trained a classification
      algorithm on the fMRI activity patterns from the presentation phase of the STM
      task to predict the order of the items during the subsequent recognition phase.
      While voxels in a number of brain regions represented positional information
      during either presentation and recognition phases, only voxels in the lateral
      prefrontal cortex (PFC) and the anterior temporal lobe (ATL) represented position
      consistently across task phases. A shared positional code in the ATL might
      reflect verbal recoding of visual sequences to facilitate the maintenance of
      order information over several seconds.

PMID- 28450142
TI  - Pan-genome analysis of Clostridium botulinum reveals unique targets for drug
      development.
AB  - Clostridium botulinum, a formidable pathogen is responsible for the emerging
      cause of food poisoning cases on the global canvas. The endemicity of bacterium
      Clostridium botulinum is reflected by the sudden hospital outbreaks and increased
      resistance towards multiple drugs. Therefore, a combined approach of in-silico
      comparative genomic analysis with statistical analysis was applied to overcome
      the limitation of bench-top technologies. Owing to the paucity of genomic data
      available by the advent of third generation sequencing technologies, several
      'omics' technologies were applied to understand the underlying evolutionary
      pattern and lifestyle of the bacterial pathogen using phylogenomics. The
      calculation of pan-genome, core genome and singletons provides view of genetic
      repertoire of the bacterial pathogen lineage at the successive level, orthology
      shared and specific gene subsets. In addition, assessment of pathogenomic
      potential, resistome, toxin/antitoxin family in successive pathogenic strains of
      Clostridium botulinum aids in revealing more specific targets for drug design and
      development.

PMID- 28450144
TI  - While Mortality Rates Differ After Dysvascular Partial Foot and Transtibial
      Amputation, Should They Influence the Choice of Amputation Level?
AB  - Although there is strong evidence to show that the risk of dying after
      transtibial amputation is higher than partial foot amputation, we are concerned
      by the implication that amputation level influences mortality, and that such
      interpretations of the evidence may be used to inform decisions about the choice
      of amputation level. We argue that the choice of partial foot or transtibial
      amputation does not influence the risk of mortality. The highest mortality rates
      are observed in studies with older people with more advanced systemic disease and
      multiple comorbidities. Studies that control for the confounding influence of
      these factors have shown no differences in mortality rates by amputation level.
      These insights have important implications in terms of how we help inform
      difficult decisions about amputation at either the partial foot or transtibial
      level, given a more thoughtful interpretation of the published mortality rates.

PMID- 28450143
TI  - Crosstalk between nuclear and G protein-coupled estrogen receptors.
AB  - In 2005, two groups independently discovered that the G protein-coupled receptor
      GPR30 binds estradiol in cultured cells and, in response, initiates intracellular
      signaling cascades Revankar et al. (2005), Thomas et al. (2005). GPR30 is now
      referred to as GPER, the G-protein coupled estrogen receptor Prossnitz and
      Arterburn (2015). While studies in animal models are illuminating GPER function,
      there is controversy as to whether GPER acts as an autonomous estrogen receptor
      in vivo, or whether GPER interacts with nuclear estrogen receptor signaling
      pathways in response to estrogens. Here, we review the evidence that GPER acts as
      an autonomous estrogen receptor in vivo and discuss experimental approaches to
      test this hypothesis directly. We propose that the degree to which GPER
      influences nuclear estrogen receptor signaling likely depends on cell type,
      developmental stage and pathology.

PMID- 28450145
TI  - Are anaerobes a major, underappreciated cause of necrotizing infections?
AB  - Necrotizing soft tissue infections (NSTIs) are the most severe and rapidly
      progressing class of skin and soft tissue infections (SSTIs). They are a surgical
      emergency and are associated with high mortality and morbidity. While NSTIs
      remain relatively rare, their incidence is steadily rising. Earlier diagnosis and
      more focused antibiotic treatments can potentially improve patient outcome, but
      both of these solutions require a more accurate understanding of the microbial
      component of these infections. While molecular detection methods, namely 16S
      sequencing, have not been traditionally used to identify the causative
      microorganisms in NSTIs, they are becoming more commonplace for other types of
      SSTIs, especially for chronic wound infections. In chronic wound infections, 16S
      sequencing has revealed a higher than previously detected prevalence of obligate
      anaerobes. Therefore, it is possible that 16S sequencing may also detect a higher
      than expected proportion of obligate anaerobes in NSTIs. In this review, we
      discuss the current state of knowledge concerning the diagnosis and treatment of
      NSTIs and present reasons why the role of anaerobes may be significantly
      underestimated.

PMID- 28450146
TI  - Alternatives to eye bank native tissue for corneal stromal replacement.
AB  - Corneal blindness is a major cause of blindness in the world and corneal
      transplantation is the only widely accepted treatment to restore sight in these
      eyes. However, it is becoming increasingly difficult for eye banks to meet the
      increasing demand for transplantable tissue, which is in part due to population
      aging. Donor tissue shortage is therefore a growing concern globally and there is
      a need for alternatives to human donor corneas. Biosynthetic corneal substitutes
      offer several significant advantages over native corneas: Large-scale production
      offers a powerful potential solution to the severe shortage of human donor
      corneas worldwide; Good manufacturing practices ensure sterility and quality
      control; Acellular corneal substitutes circumvent immune rejection induced by
      allogeneic cells; Optical and biomechanical properties of the implants can be
      adapted to the clinical need; and finally these corneal substitutes could benefit
      from new advances in biomaterials science, such as surface coating,
      functionalization and nanoparticles. This review highlights critical
      contributions from laboratories working on corneal stromal substitutes. It
      focuses on synthetic inert prostheses (keratoprostheses), acellular scaffolds
      with and without enhancement of endogenous regeneration, and cell-based
      replacements. Accent is put on the physical properties and biocompatibility of
      these biomaterials, on the functional and clinical outcome once transplanted in
      vivo in animal or human eyes, as well as on the main challenges of corneal
      stromal replacement. Regulatory and economic aspects are also discussed. All of
      these perspectives combined highlight the founding principles of the clinical
      application of corneal stromal replacement, a concept that has now become
      reality.

PMID- 28450147
TI  - Introduction to Special Issue "Redox regulation of cardiovascular signaling in
      health and disease".

PMID- 28450148
TI  - Sulfonation of the resolving cysteine in human peroxiredoxin 1: A comprehensive
      analysis by mass spectrometry.
AB  - Peroxiredoxin 1 (Prx1) is an essential peroxidase that reduces cellular
      peroxides. It holds 2 indispensable cysteines for its activity: a peroxidatic
      cysteine (CP) for peroxide reduction and a resolving cysteine (CR) for CP
      regeneration. CP can be readily sulfonated to CP-SO3H by protracted oxidative
      stress, which inactivates Prx1 as a peroxidase. By comparison, sulfonation of CR
      to CR-SO3H in mammalian cells has only been reported once. The rare report of CR
      sulfonation prompts the following questions: "can CR-SO3H be detected more
      readily with the current high sensitivity mass spectrometers (MS)?" and "do CP
      and CR have distinct propensities to sulfonation?" Answers to these questions
      could shed light on how differential sulfonation of CP and CR regulates Prx1
      functions in cells. We used a sensitive Orbitrap MS to analyze both basal and
      H2O2-induced sulfonation of CR and CP in either recombinant human Prx1 (rPrx1) or
      HeLa cell Prx1 (cPrx1). In the Orbitrap MS, we optimized both collision-induced
      dissociation and higher-energy collisional dissociation methods to improve the
      analytical sensitivity of cysteine sulfonation. In the basal states without added
      H2O2, both CP and CR were partially sulfonated in either rPrx1 or cPrx1. Still,
      exogenous H2O2 heightened the sulfonation levels of both CP and CR by ~200-700%.
      Titration with H2O2 revealed that CP and CR possessed distinct propensities to
      sulfonation. This surprising discovery of prevalent Prx1 CR sulfonation affords a
      motivation for future investigation of its precise functions in cellular stress
      response.

PMID- 28450149
TI  - Free radical production and antioxidant status in brain cortex non-synaptic
      mitochondria and synaptosomes at alcohol hangover onset.
AB  - Alcohol hangover (AH) is the pathophysiological state after a binge-like
      drinking. We have previously demonstrated that AH induced bioenergetics
      impairments in a total fresh mitochondrial fraction in brain cortex and
      cerebellum. The aim of this work was to determine free radical production and
      antioxidant systems in non-synaptic mitochondria and synaptosomes in control and
      hangover animals. Superoxide production was not modified in non-synaptic
      mitochondria while a 17.5% increase was observed in synaptosomes. A similar
      response was observed for cardiolipin content as no changes were evidenced in non
      synaptic mitochondria while a 55% decrease in cardiolipin content was found in
      synaptosomes. Hydrogen peroxide production was 3-fold increased in non-synaptic
      mitochondria and 4-fold increased in synaptosomes. In the presence of deprenyl,
      synaptosomal H2O2 production was 67% decreased in the AH condition. Hydrogen
      peroxide generation was not affected by deprenyl addition in non-synaptic
      mitochondria from AH mice. MAO activity was 57% increased in non-synaptic
      mitochondria and 3-fold increased in synaptosomes. Catalase activity was 40% and
      50% decreased in non-synaptic mitochondria and synaptosomes, respectively.
      Superoxide dismutase was 60% decreased in non-synaptic mitochondria and 80%
      increased in synaptosomal fractions. On the other hand, GSH (glutathione) content
      was 43% and 17% decreased in synaptosomes and cytosol. GSH-related enzymes were
      mostly affected in synaptosomes fractions by AH condition. Acetylcholinesterase
      activity in synaptosomes was 11% increased due to AH. The present work reveals
      that AH provokes an imbalance in the cellular redox homeostasis mainly affecting
      mitochondria present in synaptic terminals.

PMID- 28450150
TI  - Late mitral restenosis after percutaneous commissurotomy: Predictive value of
      inflammation and extracellular matrix remodeling biomarkers.
AB  - BACKGROUND: The role of chronic inflammation in mitral restenosis after
      percutaneous mitral commissurotomy (PMC) is still controversial. AIMS: We sought
      to assess the predictive value of inflammation and extracellular matrix (ECM)
      remodeling biomarkers in late mitral restenosis after PMC. METHODS: We
      prospectively enrolled 155 patients (mean age 46.2+/-11 years) with at least 5
      year follow up after primary PMC. Serum levels of high sensitive C-Reactive
      Protein (hs-CRP), matrix metalloproteinases MMPs, tissue-specific inhibitors of
      matrix metalloproteinases TIMPs, and tumor necrosis factor alpha (TNFalpha)] were
      measured. RESULTS: Late mitral restenosis occurred in 55 patients (35.5%). The
      independent predictors of late mitral stenosis were: age> 55 years [HR10.51
      (95%CI 1.12-95.9); p=0.037]; no long acting penicillin therapy [HR 18.1 (95% CI
      2.6-122.9); p=0.003]; TNFalpha > 80 ng/ml [HR 5.85 (95% CI 1.1-31.42); p=0.039];
      and TIMP-2 > 289 ng/ml [HR 0.52 (95% CI 0.22-0.95); p=0.045]. CONCLUSION: Chronic
      inflammation and ECM remodeling are involved in late mitral restenosis after PMC.

PMID- 28450151
TI  - Quercetin, a natural product supplement, impairs mitochondrial bioenergetics and
      locomotor behavior in larval zebrafish (Danio rerio).
AB  - Quercetin is a natural product that is sold as a supplement in health food
      stores. While there are reported benefits for this flavonoid as a dietary
      supplement due to antioxidant properties, the full scope of its biological
      interactions has not been fully addressed. To learn more about the mechanisms of
      action related to quercetin, we exposed zebrafish (Danio rerio) embryos to 1 and
      10MUg/L quercetin for 96h starting at 3h post fertilization. Quercetin up to
      10MUg/L did not induce significant mortality in developing fish, but did increase
      prevalence of an upward-curved dorsal plane in hatched larvae. To determine
      whether this developmental defect was potentially related to mitochondrial
      bioenergetics during development, we measured oxygen consumption rate in whole
      embryos following a 24-hour exposure to quercetin. Basal mitochondrial and ATP
      linked respiration were decreased at 1 and 10MUg/L quercetin, and maximal
      respiration was decreased at 10MUg/L quercetin, suggesting that quercetin impairs
      mitochondrial bioenergetics. This is proposed to be related to the deformities
      observed during development. Due to the fact that ATP production was affected by
      quercetin, larval behaviors related to locomotion were investigated, as well as
      transcriptional responses of six myogenesis transcripts. Quercetin at 10MUg/L
      significantly reduced the swimming velocity of zebrafish larvae. The expression
      levels of both myostatin A (mstna) and myogenic differentiation (myoD) were also
      altered by quercetin. Mstna, an inhibitory factor for myogenesis, was
      significantly increased at 1MUg/L quercetin exposure, while myoD, a stimulatory
      factor for myogenesis, was significantly increased at 10MUg/L quercetin exposure.
      There were no changes in transcripts related to apoptosis (bcl2, bax, casp3,
      casp7), but we did observe a decrease in mRNA levels for catalase (cat) in fish
      exposed to each dose, supporting an oxidative stress response. Our data support
      the hypothesis that quercetin may affect locomotion and induce deformities in
      zebrafish larvae by diminishing ATP production and by altering the expression of
      transcripts related to muscle formation and activity.

PMID- 28450152
TI  - Early deprivation increases high-leaning behavior, a novel anxiety-like behavior,
      in the open field test in rats.
AB  - The open field test is one of the most popular ethological tests to assess
      anxiety-like behavior in rodents. In the present study, we examined the effect of
      early deprivation (ED), a model of early life stress, on anxiety-like behavior in
      rats. In ED animals, we failed to find significant changes in the time spent in
      the center or thigmotaxis area of the open field, the common indexes of anxiety
      like behavior. However, we found a significant increase in high-leaning behavior
      in which animals lean against the wall standing on their hindlimbs while touching
      the wall with their forepaws at a high position. The high-leaning behavior was
      decreased by treatment with an anxiolytic, diazepam, and it was increased under
      intense illumination as observed in the center activity. In addition, we compared
      the high-leaning behavior and center activity under various illumination
      intensities and found that the high-leaning behavior is more sensitive to
      illumination intensity than the center activity in the particular illumination
      range. These results suggest that the high-leaning behavior is a novel anxiety
      like behavior in the open field test that can complement the center activity to
      assess the anxiety state of rats.

PMID- 28450153
TI  - Epidural focal brain cooling abolishes neocortical seizures in cats and non-human
      primates.
AB  - Focal brain cooling (FBC) is under investigation in preclinical trials of
      intractable epilepsy (IE), including status epilepticus (SE). This method has
      been studied in rodents as a possible treatment for epileptic disorders, but more
      evidence from large animal studies is required. To provide evidence that FBC is a
      safe and effective therapy for IE, we investigated if FBC using a titanium
      cooling plate can reduce or terminate focal neocortical seizures without having a
      significant impact on brain tissue. Two cats and two macaque monkeys were
      chronically implanted with an epidural FBC device over the somatosensory and
      motor cortex. Penicillin G was delivered via the intracranial cannula for
      induction of local seizures. Repetitive FBC was performed using a cooling device
      implanted for a medium-term period (FBC for 30min at least twice every week; 3
      months total) in three of the four animals. The animals exhibited seizures with
      repetitive epileptiform discharges (EDs) after administration of penicillin G,
      and these discharges decreased at less than 20 degrees C cooling with no adverse
      histological effects. The results of this study suggest that epidural FBC is a
      safe and effective potential treatment for IE and SE.

PMID- 28450154
TI  - Phenyl butyrate inhibits pyruvate dehydrogenase kinase 1 and contributes to its
      anti-cancer effect.
AB  - Phenyl butyrate (PB) has been proved to decrease pyruvate dehydrogenase (PDH)
      phosphorylation level and increase PDH activity by inhibiting pyruvate
      dehydrogenase kinase 1 (PDK1) in fibroblast cells, PDH deficiency zebrafish and
      wild type mice. PB has also shown efficacy in many cancers and so far, all of its
      anti-tumor activity has been attributed to the histone deacetylase (HDAC)
      inhibition. As PDK1/PDH controls the critical switch between oxidative
      phosphorylation and glycolysis in cancer cells, PDK1 is a key target in tumor
      metabolism for anti-cancer treatment. We hypothesize that the therapeutic effects
      of PB in cancers might also depend on suppressing PDK1 and promoting PDH
      activity, in addition to its proposed role as HDAC inhibitor. We showed that PB
      directly inhibited the kinase activity of PDK1 and increased the activity of PDH
      in an enzyme assay. In several different cancer cell lines, PB reduced the
      phosphorylation level of PDH, increased the mitochondrial respiration, decreased
      glycolysis in cytoplasm, reversed mitochondrial hyperpolarization, activated
      several proteins in apoptotic signaling pathway and then induced the apoptosis of
      cells. In summary, this is the first study indicated that PB could exert its anti
      cancer effects through inhibiting PDK1, altering the mitochondrial bioenergetics
      and inducing apoptosis.

PMID- 28450155
TI  - Ionised concentrations in calcium and magnesium buffers: Standards and precise
      measurement are mandatory.
AB  - In Ca2+ and Mg2+ buffer solutions the ionised concentrations ([X2+]) are either
      calculated or measured. Calculated values vary by up to a factor of seven due to
      the following four problems: The calculated [X2+] in buffers are so inconsistent
      that calculation is not an option. Until standards are available, the [X2+] in
      the buffers must be measured. The Ligand Optimisation Method is an accurate and
      independently verified method of doing this (McGuigan & Stumpff, Anal. Biochem.
      436, 29, 2013). Lack of standards means it is not possible to compare the
      published [Ca2+] in the nmolar range, and the apparent constant (K/) values for
      Ca2+ and Mg2+ binding to intracellular ligands amongst different laboratories.
      Standardisation of Ca2+/Mg2+ buffers is now essential. The parameters to achieve
      this are proposed.

PMID- 28450156
TI  - microRNA-7 impairs autophagy-derived pools of glucose to suppress pancreatic
      cancer progression.
AB  - Pancreatic cancer commonly addicts to aerobic glycolysis, and abnormally
      activates autophagy to adapt the stringent metabolic microenvironment. microRNA-7
      (miR-7) was supposed to modulate various gastrointestinal cancer progression. We
      wonder whether miR-7 could destroy the reprogrammed metabolic homeostasis in
      pancreatic cancer via modulating the level of autophagy, and further affect tumor
      proliferation and survival. Herein, we first reported that pancreatic cancer
      could take advantage of autophagy as a survival strategy to provide essential
      glucose required for glycolysis metabolism. Of note, under the stressful tumor
      microenvironment, miR-7 could repress autophagy through up-regulation of LKB1
      AMPK-mTOR signaling, and directly targeting the stages of autophagy induction and
      vesicle elongation to reduce the supply of intracellular glucose to glycolysis
      metabolism. Furthermore, miR-7 inhibited pancreatic cancer cell proliferation and
      metastasis in vitro and in vivo. Consistently, lentivirus-mediated miR-7
      effectively reduced the growth of patient-derived xenograft by interfering
      glycolysis via inhibition of autophagy. Together, these data suggested miR-7
      might function as an important regulator to impair autophagy-derived pools of
      glucose to suppress pancreatic cancer progress. Hence, miR-7 might be a potential
      therapeutic target in pancreatic cancer.

PMID- 28450158
TI  - The ErbB family and androgen receptor signaling are targets of Celecoxib in
      prostate cancer.
AB  - Inflammation plays a central role in prostate cancer (PCa) development through
      significant crosstalk between the COX-2-ErbB family receptor network and androgen
      receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine
      the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling
      pathway in androgen-dependent PCa cells and to provide a rationale for its
      beneficial use in chemopreventive strategies. Functional studies of Celecoxib
      activity were performed on LNCaP prostate cancer cells. Western blotting, gene
      expression analysis, dual-luciferase reporter assay and ELISA were applied to
      assess the Celecoxib mechanisms of action. We found that Celecoxib, through EGF
      and amphiregulin (AREG) induction, caused EGFR and ErbB2 activation and
      consequent degradation associated with the inhibition of androgenic signaling. By
      upregulating the E3 ubiquitin ligase Nrdp1, Celecoxib also efficiently
      downregulated ErbB3, which is strongly implicated in castration-resistant
      prostate cancer. Lastly, Celecoxib directly regulated AR transcription and
      translation independent of ErbB activation by downregulating the RNA binding
      protein heterogeneous nuclear ribonucleoprotein K (hnRNP K). The simultaneous
      suppression of ErbB kinases and androgen signaling by Celecoxib represents a
      novel strategy to interrupt the vicious cycle of AR/ErbB cross-talk with the
      primary purpose of undermining their resilient signaling in prostate cancer
      progression. Our data provide important premises for the chemopreventive use of
      Celecoxib in the clinical management of prostate cancer.

PMID- 28450157
TI  - The dual mTOR kinase inhibitor TAK228 inhibits tumorigenicity and enhances
      radiosensitization in diffuse intrinsic pontine glioma.
AB  - Diffuse intrinsic pontine glioma (DIPG) is an invasive and treatment-refractory
      pediatric brain tumor. Primary DIPG tumors harbor a number of mutations including
      alterations in PTEN, AKT, and PI3K and exhibit activation of mammalian Target of
      Rapamycin Complex 1 and 2 (mTORC1/2). mTORC1/2 regulate protein translation, cell
      growth, survival, invasion, and metabolism. Pharmacological inhibition of mTORC1
      is minimally effective in DIPG. However, the activity of dual TORC kinase
      inhibitors has not been examined in this tumor type. Nanomolar levels of the
      mTORC1/2 inhibitor TAK228 reduced expression of p-AKTS473 and p-S6S240/244 and
      suppressed the growth of DIPG lines JHH-DIPG1, SF7761, and SU-DIPG-XIII. TAK228
      induced apoptosis in DIPG cells and cooperated with radiation to further block
      proliferation and enhance apoptosis. TAK228 monotherapy inhibited the
      tumorigenicity of a murine orthotopic model of DIPG, more than doubling median
      survival (p = 0.0017) versus vehicle. We conclude that dual mTOR inhibition is a
      promising potential candidate for DIPG treatment.

PMID- 28450159
TI  - Spatial and temporal patterns of nasopharyngeal carcinoma mortality in China,
      1973-2005.
AB  - We fitted generalized linear models using data from three national retrospective
      surveys on cause of death in China to explore the spatial and temporal patterns
      of nasopharyngeal carcinoma (NPC) mortality over the period 1973 to 2005. The
      results suggest that there was a significant decrease in NPC mortality in China
      over time (p < 0.0001), the mortality rate ratio (RR) for the two later time
      periods were 0.59 (95% CI: 0.55-0.64) for 1990-1992 and 0.42 (95% CI: 0.39-0.45)
      for 2004-2005 compared to that of 1973-1975. Residents living in the South China
      areas have an elevated risk of mortality from NPC compared to those living in
      North China across all three time periods, with the RR being 4.96 (95% CI: 4.31
      5.70) in 1973-1975, 12.83 (95% CI: 10.73-15.34) in 1990-1992 and 15.20 (95% CI:
      12.34-18.72) in 2004-2005. Although NPC mortality in most areas of China has
      reduced to very low levels, the widening geographical disparities in NPC
      mortality are still noteworthy. It may be necessary to target public health
      policies to address the widening geographical disparities in NPC mortality.

PMID- 28450160
TI  - A novel histone deacetylase inhibitor TMU-35435 enhances etoposide cytotoxicity
      through the proteasomal degradation of DNA-PKcs in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) treatment offers only limited benefits, and
      it is very relevant given the significant number of deaths that it causes. DNA
      repair pathways can enable tumor cells to survive DNA damage that is induced by
      chemotherapeutic or radiation treatments. Histone deacetylase inhibitors (HDACi)
      inhibited DNA repair proteins. However, the detailed mechanisms for this
      inhibition remain unclear. In the present study, we investigated whether a newly
      developed HDACi, TMU-35435, could enhance etoposide cytotoxicity by inhibiting
      DNA repair proteins in triple-negative breast cancer. We found synergistic
      cytotoxicity following treatment of 4T1 cells with etoposide and TMU-35435.
      Furthermore, TMU-35435 enhances etoposide-induced DNA damage by inhibiting the
      DNA repair pathway (non-homologous end joining, NHEJ). TMU-35435 suppresses the
      NHEJ pathway through the ubiquitination of DNA-dependent protein kinase catalytic
      subunit (DNA-PKcs). In addition, TMU-35435 ubiquitinated DNA-PKcs by inducing the
      interaction between RNF144A (an E3 ligase) and DNA-PKcs. The combined treatment
      induced apoptosis and autophagic cell death in 4T1 cells. In an orthotopic breast
      cancer model, combined treatment with TMU-35435 and etoposide showed anti-tumor
      growth through the increase of DNA damage and cell death. Taken together, our
      data suggest that TMU-35435 enhances etoposide cytotoxicity by regulating
      ubiquitin-proteasome system and inhibiting the DNA repair pathway in TNBC.

PMID- 28450161
TI  - A perillyl alcohol-conjugated analog of 3-bromopyruvate without cellular uptake
      dependency on monocarboxylate transporter 1 and with activity in 3-BP-resistant
      tumor cells.
AB  - The anticancer agent 3-bromopyruvate (3-BP) is viewed as a glycolytic inhibitor
      that preferentially kills glycolytic cancer cells through energy depletion.
      However, its cytotoxic activity is dependent on cellular drug import through
      transmembrane monocarboxylate transporter 1 (MCT-1), which restricts its
      anticancer potential to MCT-1-positive tumor cells. We created and characterized
      an MCT-1-independent analog of 3-BP, called NEO218. NEO218 was synthesized by
      covalently conjugating 3-BP to perillyl alcohol (POH), a natural monoterpene. The
      responses of various tumor cell lines to treatment with either compound were
      characterized in the presence or absence of supplemental pyruvate or antioxidants
      N-acetyl-cysteine (NAC) and glutathione (GSH). Drug effects on glyceraldehyde 3
      phosphate dehydrogenase (GAPDH) enzyme activity were investigated by mass
      spectrometric analysis. The development of 3-BP resistance was investigated in
      MCT-1-positive HCT116 colon carcinoma cells in vitro. Our results show that
      NEO218: (i) pyruvylated GAPDH on all 4 of its cysteine residues and shut down
      enzymatic activity; (ii) severely lowered cellular ATP content below life
      sustaining levels, and (iii) triggered rapid necrosis. Intriguingly, supplemental
      antioxidants effectively prevented cytotoxic activity of NEO218 as well as 3-BP,
      but supplemental pyruvate powerfully protected cells only from 3-BP, not from
      NEO218. Unlike 3-BP, NEO218 exerted its potent cytotoxic activity irrespective of
      cellular MCT-1 status. Treatment of HCT116 cells with 3-BP resulted in prompt
      development of resistance, based on the emergence of MCT-1-negative cells. This
      was not the case with NEO218, and highly 3-BP-resistant cells remained
      exquisitely sensitive to NEO218. Thus, our study identifies a mechanism by which
      tumor cells develop rapid resistance to 3-BP, and presents NEO218 as a superior
      agent not subject to this cellular defense. Furthermore, our results offer
      alternative interpretations of previously published models on the role of
      supplemental antioxidants: Rather than quenching reactive oxygen species (ROS),
      supplemental NAC or GSH directly interact with 3-BP, thereby neutralizing the
      drug's cytotoxic potential before it can trigger ROS production. Altogether, our
      study introduces new aspects of the cytotoxic mechanism of 3-BP, and
      characterizes NEO218 as an analog able to overcome a key cellular defense
      mechanism towards this drug.

PMID- 28450162
TI  - Structure and ultrastructure of the ovary in the South American Veturius sinuatus
      (Eschscholtz) (Coleoptera, Passalidae).
AB  - The morphoanatomy of the ovary in Veturius sinuatus (Eschscholtz) was studied by
      light and transmission electron microscopy. Data from the female gonad of this
      species provide more extended and precise knowledge regarding the organization of
      the ovary in Passalidae. Ovaries are composed of a pair of long telotrophic
      meroistic ovarioles, with some differences compared to the bauplan of this ovary
      type in Polyphaga (Coleoptera). The terminal filament has an enlarged proximal
      region with irregularly shaped cells in apparent degeneration process embedded in
      a membranous system. Globular structures with amorphous content associated with
      interstitial cells are distributed throughout the tropharium. Trophocytes develop
      with the reduction of the plasma membrane between sibling nurse cells of each
      cluster. Previtellogenic oocytes have an irregular shape and various cytoplasmic
      prolongations. As oogenesis advances, a single prolongation in the anterior part
      of the oocyte extends to the tropharium. The ovary structure is comparable to
      that found in other American species of passalids, and further, the conformation
      of the terminal filament could be a plesiomorphic character of the family.

PMID- 28450163
TI  - Murine hemogenic endothelial precursors display heterogeneous hematopoietic
      potential ex vivo.
AB  - Hematopoietic stem and progenitor cells (HSPCs) sustain life-long hematopoiesis
      and are first detected in the embryo by transplantation at embryonic day 10.5
      (E10.5). HSPCs are mesodermal in origin and ultimately emerge from a subset of
      arterial endothelium (i.e., hemogenic endothelium [HE]), which is highly
      concentrated in the aorta-gonad-mesonephros region of the midgestation embryo.
      Here, we used clonal ex vivo assays, in which endothelial cells isolated from the
      midgestation aorta and vitelline and umbilical arteries are co-cultured on
      supportive stroma, to show that only about 0.1%, 1.3%, and 0.29% of E9.5, E10.5,
      and E11.5 endothelium are functional HE, respectively. We further show high
      phenotypic and functional variability in the hematopoietic potential of
      individual hemogenic endothelial precursors. Using unique niche stroma capable of
      providing the signals necessary for definitive hematopoietic stem cell (dHSC)
      induction, we demonstrate that this variability in HE includes their potential to
      support phenotypic dHSCs. These data suggest the presence of a continuum of
      maturing HE with distinct hematopoietic potential or HE representative of a
      heterogeneous pool of precursors that give rise to HSPCs with disparate
      hematopoietic potential.

PMID- 28450164
TI  - A novel approach to study the pMDI plume using an infrared camera and to evaluate
      the aerodynamic properties after varying the time between actuations.
AB  - Plume characteristics, such as temperature and velocity, emitted from pMDIs could
      significantly affect the dose delivered to the lung. Currently, high speed
      cameras and thermocouples are used separately to evaluate these parameters. We
      used a low-noise infrared camera to evaluate both the temperature and velocity of
      the emitted plume from pMDIs. Additionally, we investigated whether the fine
      particle fraction (FPF) is affected when time between actuations is varied. We
      tested three different albuterol sulfate pMDIs: ProAir(r) HFA, Proventil(r) HFA,
      and Ventolin(r) HFA. The plume and aerodynamic characteristics from these pMDIs
      were evaluated, after varying the time between actuations (15, 30, 60, and 120s),
      using the infrared camera and a next generation impactor, respectively. The
      aerodynamic characteristics were evaluated with and without a valved holding
      chamber (VHC). ProAir HFA had the softest plume followed by Proventil HFA and
      Ventolin HFA. Further, Ventolin HFA was slightly cooler and had significantly
      lower FPF than ProAir HFA and Proventil HFA. All inhalers had higher FPF when
      used with VHC. Further, we observed that the time between actuations affected the
      FPF across pMDIs. Moreover, generalized guidelines suggesting one-minute interval
      between actuations for pMDIs should be reconsidered, with and without a VHC.

PMID- 28450165
TI  - Effect of guest drug character encapsulated in the cavity and intermolecular
      spaces of gamma-cyclodextrins on the dissolution property of ternary gamma
      cyclodextrin complex.
AB  - Various ternary Guest 2/(Guest 1/gamma-cyclodextrin (CD)) complexes were prepared
      using a cogrinding and subsequent heating method, wherein Guest 1 was
      incorporated in the cavity of gamma-CD and Guest 2 was incorporated into the
      intermolecular spaces between gamma-CD columns. Dissolution fluxes of Guest 1 and
      Guest 2 from all ternary complexes were almost identical. The dissolution flux of
      flurbiprofen (Guest 1) from the ternary complexes depended on the solubility of
      Guest 2 drugs (naproxen<ketoprofen<ethenzamide) in the dissolution medium of pH
      1.2. It is noteworthy that the dissolution flux of flurbiprofen from the ternary
      complexes with ketoprofen and ethenzamide as Guest 2 drugs was further enhanced
      compared with that from the flurbiprofen/gamma-CD inclusion complex. The ternary
      complex of the acidic drug ketoprofen as Guest 1 and the neutral drug
      hydrocortisone as Guest 2 showed an increased dissolution flux, which was
      dependent on the increase in pH of the dissolution medium. The pH-dependent
      dissolution should reflect the solubility of ketoprofen/gamma-CD inclusion
      complex in each dissolution medium. These results indicated that the dissolution
      flux of the ternary gamma-CD complexes could be controlled by selecting the
      appropriate Guest 1 and Guest 2 species.

PMID- 28450167
TI  - Gastrointestinal behavior of itraconazole in humans - Part 2: The effect of
      intraluminal dilution on the performance of a cyclodextrin-based solution.
AB  - Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is known to enable absorption of the
      lipophilic drug itraconazole. Since the interaction between HP-beta-CD and
      itraconazole is characterized by a non-lineair, AP-type phase-solubility diagram,
      the present study aimed to investigate the influence of intraluminal dilution
      (water intake) on the behavior and performance of an orally administered
      cyclodextrin-based solution of itraconazole. Subsequently, the in vivo behavior
      was simulated by combining in vitro dilution with permeation assessment. After
      the administration of a Sporanox(r) solution to healthy volunteers with or
      without a glass of water, gastrointestinal and systemic concentrations of
      itraconazole were simultaneously monitored. Independently of the intake of water,
      no gastric precipitation of itraconazole was observed. After transfer to the
      duodenum, precipitation occurred and was more pronounced in the condition with
      water, resulting in a 7.6-fold reduction in duodenal AUC0-3h compared to the
      condition without water. Nevertheless, plasma concentration-time profiles did not
      demonstrate any significant differences in AUC0-8h, Cmax and tmax. Application of
      freshly aspirated intestinal fluids on Caco-2 cells clearly confirmed that higher
      intestinal itraconazole concentrations after intake of Sporanox(r) without water
      do not generate a substantially increased itraconazole uptake. A two-stage in
      vitro dilution test was combined with a permeation compartment to capture this
      solubility-permeability interplay. In conclusion, this work demonstrates that
      variations in intraluminal dilution may have a drastic impact on the
      gastrointestinal behavior of lipophilic drugs in the presence of cyclodextrins.
      In the case of an AP-type interaction with cyclodextrins, the trade-off between
      solubility and permeability may be affected.

PMID- 28450166
TI  - Development and physicochemical characterization of acetalated dextran aerosol
      particle systems for deep lung delivery.
AB  - Biocompatible, biodegradable polymers are commonly used as excipients to improve
      the drug delivery properties of aerosol formulations, in which acetalated dextran
      (Ac-Dex) exhibits promising potential as a polymer in various therapeutic
      applications. Despite this promise, there is no comprehensive study on the use of
      Ac-Dex as an excipient for dry powder aerosol formulations. In this study, we
      developed and characterized pulmonary drug delivery aerosol microparticle systems
      based on spray-dried Ac-Dex with capabilities of (1) delivering therapeutics to
      the deep lung, (2) targeting the particles to a desired location within the
      lungs, and (3) releasing the therapeutics in a controlled fashion. Two types of
      Ac-Dex, with either rapid or slow degradation rates, were synthesized.
      Nanocomposite microparticle (nCmP) and microparticle (MP) systems were
      successfully formulated using both kinds of Ac-Dex as excipients and curcumin as
      a model drug. The resulting MP were collapsed spheres approximately 1MUm in
      diameter, while the nCmP were similar in size with wrinkled surfaces, and these
      systems dissociated into 200nm nanoparticles upon reconstitution in water. The
      drug release rates of the Ac-Dex particles were tuned by modifying the particle
      size and ratio of fast to slow degrading Ac-Dex. The pH of the environment was
      also a significant factor that influenced the drug release rate. All nCmP and MP
      systems exhibited desirable aerodynamic diameters that are suitable for deep lung
      delivery (e.g. below 5MUm). Overall, the engineered Ac-Dex aerosol particle
      systems have the potential to provide targeted and effective delivery of
      therapeutics into the deep lung.

PMID- 28450168
TI  - Tuning complement activation and pathway through controlled molecular
      architecture of dextran chains in nanoparticle corona.
AB  - The understanding of complement activation by nanomaterials is a key to a
      rational design of safe and efficient nanomedicines. This work proposed a
      systematic study investigating how molecular design of nanoparticle coronas made
      of dextran impacts on mechanisms that trigger complement activation. The
      nanoparticles used for this work consisted of dextran-coated
      poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly
      characterized. Their different capacity to trigger complement activation
      established on the cleavage of the protein C3 was also already described making
      these nanoparticles good models to investigate the relation between the molecular
      feature of their corona and the mechanism by which they triggered complement
      activation. Results of this new study show that complement activation pathways
      can be selected by distinct architectures formed by dextran chains composing the
      nanoparticle corona. Assumptions that explain the relation between complement
      activation mechanisms triggered by the nanoparticles and the nanoparticle corona
      molecular feature were proposed. These results are of interest to better
      understand how the design of dextran-coated nanomaterials will impact
      interactions with the complement system. It can open perspectives with regard to
      the selection of a preferential complement activation pathway or prevent the
      nanoparticles to activate the complement system, based on a rational choice of
      the corona configuration.

PMID- 28450169
TI  - Limiting the level of tertiary amines on polyamines leads to biocompatible
      nucleic acid vectors.
AB  - We have designed an efficient, synthetic nucleic acid vector, which is relatively
      non-toxic. [N-(2-ethylamino)-6-O-glycolchitosan - EAGC] polymers were 10-50 fold
      less toxic than Lipofectamine 2000, able to complex DNA, mRNA and siRNA into
      positively charged (zeta potential=+40 - 50mV), 50-450nm nanoparticles. The level
      of tertiary amine N-2-ethylamino substitution (DStert) was inversely proportional
      to the IC50 of the EAGC polymers in the A431 cell line: IC50=6.18DStert-0.9,
      r2=0.9991. EAGC polyplexes were stable against a heparin challenge, able to
      protect the nucleic acids from nuclease degradation and achieve levels of
      transfection comparable to Lipofectamine 2000 formulations. The relative
      biocompatibility of the vector allowed 10 fold higher doses of DNA (1MUg compared
      to 0.1MUg per well with Lipofectamine 2000) and siRNA (10.7MUg per well vs 1.3MUg
      with Lipofectamine 2000) to be applied to cells, when compared to Lipofectamine
      2000. Finally intranasal application of EAGC - siRNA complexes resulted in siRNA
      transfer to the neurons of the olfactory bulb.

PMID- 28450170
TI  - Use of acidifier and solubilizer in tadalafil solid dispersion to enhance the in
      vitro dissolution and oral bioavailability in rats.
AB  - The purpose of this study is to improve the solubility, in vitro dissolution, and
      oral bioavailability in rats of tadalafil (TDF) by using SD technique with a weak
      acid and a copolymer. TDF-SD was prepared via solvent evaporation, coupled with
      the incorporation of an acidifier and solubilizer. Tartaric acid enhanced the
      solubility of TDF over 5-fold in DW, and Soluplus(r) enhanced the solubility of
      TDF over 8.7-fold and 19.2-fold compared to that of TDF (pure) in DW and pH 1.2
      for 1h, respectively. The optimal formulation of TDF-SD3 was composed of TDF vs
      Tartaric acid vs Soluplus(r) vs Aerosil=1:1:3:3. The in vitro dissolution rate of
      TDF-SD3 in DW, pH 1.2 and pH 6.8 buffer (51.5%, 53.3%, and 33.2%, respectively)
      was significantly higher than that of the commercial product (Cialis(r)) powder
      (16.5%, 15.2%, and 14.8%, respectively). TDF was completely transformed to an
      amorphous form as shown in SEM, DSC and PXRD data. The stability of TDF-SD3
      included drug contents and in vitro dissolution for 1 month were similar to those
      of Cialis(r), and the amorphous form of TDF-SD3 was well maintained for 6 months.
      The TDF-SD3 formulation improved the relative bioavailability (BA) and peak
      plasma concentration (Cmax) compared to that of Cialis(r) powder after oral
      administration in rats as 117.3% and 135.7%, respectively. From the results, we
      found that the acidifier increased the wettability of TDF, and the solubilizer
      improved solubility through hydrogen bonding with TDF, thereby increasing the
      solubility, dissolution and oral bioavailability of TDF in TDF-SD3.

PMID- 28450171
TI  - Optimization of critical quality attributes in continuous twin-screw wet
      granulation via design space validated with pilot scale experimental data.
AB  - In this study, the influence of key process variables (screw speed, throughput
      and liquid to solid (L/S) ratio) of a continuous twin screw wet granulation
      (TSWG) was investigated using a central composite face-centered (CCF)
      experimental design method. Regression models were developed to predict the
      process responses (motor torque, granule residence time), granule properties
      (size distribution, volume average diameter, yield, relative width, flowability)
      and tablet properties (tensile strength). The effects of the three key process
      variables were analyzed via contour and interaction plots. The experimental
      results have demonstrated that all the process responses, granule properties and
      tablet properties are influenced by changing the screw speed, throughput and L/S
      ratio. The TSWG process was optimized to produce granules with specific volume
      average diameter of 150MUm and the yield of 95% based on the developed regression
      models. A design space (DS) was built based on volume average granule diameter
      between 90 and 200MUm and the granule yield larger than 75% with a failure
      probability analysis using Monte Carlo simulations. Validation experiments
      successfully validated the robustness and accuracy of the DS generated using the
      CCF experimental design in optimizing a continuous TSWG process.

PMID- 28450172
TI  - Recent advances in use of silver nanoparticles as antimalarial agents.
AB  - Malaria is one of the most common infectious diseases, which has become a great
      public health problem all over the world. Ineffectiveness of available
      antimalarial treatment is the main reason behind its menace. The failure of
      current treatment strategies is due to emergence of drug resistance in Plasmodium
      falciparum and drug toxicity in human beings. Therefore, the development of novel
      and effective antimalarial drugs is the need of the hour. Considering the huge
      biomedical applications of nanotechnology, it can be potentially used for the
      malarial treatment. Silver nanoparticles (AgNPs) have demonstrated significant
      activity against malarial parasite (P. falciparum) and vector (female Anopheles
      mosquito). It is believed that AgNPs will be a solution for the control of
      malaria. This review emphasizes the pros- and cons of existing antimalarial
      treatments and in depth discussion on application of AgNPs for treatment of
      malaria. The role of nanoparticles for site specific drug delivery and
      toxicological issues have also been discussed.

PMID- 28450173
TI  - A method for the improved detection of aerosolized influenza viruses and the male
      specific (F+) RNA coliphage MS2.
AB  - The detection of aerosolized viruses can serve as an important surveillance and
      control tool in agriculture, human health, and environmental settings. Here, we
      adapted an anion exchange resin-based method, initially developed to concentrate
      negatively charged viruses from water, to liquid impingement-based bioaerosol
      sampling. In this method, aerosolized viruses are collected in a 20ml liquid
      sample contained within widely used impingers, BioSamplers (SKC Inc., Eighty
      Four, PA), and further concentrated via adsorption to an anion exchange resin
      that is suspended within this liquid. Viral nucleic acids are then extracted from
      the resin to facilitate molecular analyses through a reduction in the effective
      sample volume. For this study, various quantities of two negatively charged
      viruses, type A and type B influenza viruses (FluMist Quadrivalent vaccine) and
      the male-specific (F+) RNA coliphage MS2 (MS2), were nebulized into a custom
      built bioaerosolization chamber, and sampled using BioSamplers with and without
      anion exchange resin. Compared to direct testing of the BioSampler liquid,
      detection was improved by 6.77* and 3.33* for type A and type B influenza
      viruses, respectively, by using the anion exchange resin. For MS2, the anion
      exchange resin method allowed for an average improvement in detection of 8.26*.

PMID- 28450174
TI  - Atorvastatin as a promising anticryptococcal agent.
AB  - Cryptococcosis caused by Cryptococcus gattii leads to pneumonia and
      meningoencephalitis, and has a high mortality rate worldwide due to the
      inadequacy of available therapy and increasing drug resistance. There is a need
      to develop effective treatments, and drug repositioning is an interesting
      alternative to achieve new strategies to treat cryptococcosis. Atorvastatin
      (ATO), a statin currently used to treat hypercholesterolaemia, was tested in this
      study as an adjuvant to control infections caused by C. gattii. Several aspects
      of the effect of ATO on the host and the yeast were evaluated, with particular
      focus on the association of ATO with fluconazole (FLC), which (i) reduced
      ergosterol content in the cell membrane and altered properties of the
      polysaccharide capsule of C. gattii; (ii) increased the production of reactive
      oxygen species by macrophages; and (iii) reduced yeast phagocytosis and the
      intracellular proliferation rate. In an animal model, infected mice treated with
      ATO + FLC showed increased survival, improved clinical condition, and reduced
      fungal burden in the lungs and brain. This study is the first to perform in vivo
      tests with ATO + FLC for the treatment of cryptococcosis. The results suggest
      that ATO may be an important adjuvant for the treatment of cryptococcosis.

PMID- 28450175
TI  - Absence of association between polymorphisms in the K13 gene and the presence of
      Plasmodium falciparum parasites at day 3 after treatment with artemisinin
      derivatives in Senegal.
AB  - In 2006, the Senegalese National Malaria Control Programme recommended
      artemisinin-based combination therapy as first-line treatment for uncomplicated
      malaria. In addition, intravenous (i.v.) injection of artesunate and artemether
      has gradually replaced quinine for the treatment of severe malaria. Mutations in
      the propeller domain of the Kelch 13 gene (K13-propeller, PF3D71343700), such as
      Y493H, R539T, I543T and C580Y, were recently associated with in vivo and in vitro
      resistance to artemisinin in Southeast Asia. However, these mutations were not
      identified in Africa. In total, 181 isolates of Plasmodium falciparum from 161
      patients from Dakar, Senegal, were collected between August 2015 and January
      2016. The K13-propeller gene of the isolates was sequenced. A search for non
      synonymous mutations in the propeller region of K13 was performed in the 181
      isolates collected from Dakar from 2015 to 2016. Three synonymous mutations were
      detected (D464D, C469C and R471R). Of 119 patients treated with i.v. artesunate
      or intramuscular artemether followed by artemether/lumefantrine, 9 patients were
      still parasitaemic on Day 3. Parasites from these nine patients were wild-type
      for K13-propeller. None of the polymorphisms known to be involved in artemisinin
      resistance in Asia were detected. These results suggest that K13 is not the best
      predictive marker for artemisinin resistance in Africa. More isolates from
      clinical failure cases or patients with delayed parasite clearance after
      treatment with artemisinin derivatives are necessary to identify new molecular
      markers.

PMID- 28450177
TI  - Ovarian cancer stem cells more questions than answers.
AB  - Epithelial ovarian cancer is a highly lethal disease, which is usually diagnosed
      at a late stage with extensive metastases in the abdominal cavity. Ovarian cancer
      either develops from the ovarian surface epithelium (OSE) or from serous intra
      epithelial carcinoma (STIC). Primary therapy consists of debulking surgery and
      platinum based chemotherapy. The success of debulking surgery depends on surgical
      skills but also on the gene signature of the tumour. Debulking surgery combined
      with first line platinum based chemotherapy, frequently leads to complete
      remission. However, most ovarian cancers relapse. Once the disease has relapsed,
      the interval between subsequent therapies decreases steadily due to rapid
      progression and therapy resistance. Research on therapy resistance of ovarian
      cancer is frequently devoted to genetic alterations in cancer cells, leading to
      drug inactivation, enhanced DNA repair mechanisms and intracellular pathway
      derangements. However the knowledge of ovarian cancer stem cells (OCSC) and the
      role they play in the development of cancer and therapy resistance is sparse. In
      this review current knowledge on the characteristics of OCSCs and the micro
      environmental mechanisms leading to the development or activation of OCSCs
      resulting in ovarian cancer is reviewed. Moreover the role of OCSC in both
      surgical and systemic therapy resistance and the relation with epithelial
      mesenchymal transformation (EMT) is discussed, as are micro-environmental signals
      leading to OCSC or EMT activation.

PMID- 28450178
TI  - Visual impairment in children with congenital Zika syndrome.
AB  - PURPOSE: To describe the visual impairment associated with ocular and
      neurological abnormalities in a cohort of children with congenital Zika syndrome
      (CZS). METHODS: This cross-sectional study included infants with microcephaly
      born in Pernambuco, Brazil, from May to December 2015. Immunoglobulin M antibody
      capture enzyme-linked immunosorbent assay for the Zika virus on the cerebrospinal
      fluid samples was positive for all infants. Clinical evaluation consisted of
      comprehensive ophthalmologic examination including visual acuity, visual function
      assessment, visual developmental milestone, neurologic examination, and
      neuroimaging. RESULTS: A total of 32 infants (18 males [56%]) were included. Mean
      age at examination was 5.7 +/- 0.9 months (range, 4-7 months). Visual function
      and visual developmental milestone could not be tested in 1 child (3%). Visual
      impairment was detected in 32 infants (100%). Retinal and/or optic nerve findings
      were observed in 14 patients (44%). There was no statistical difference between
      the patients with ocular findings and those without (P = 0.180). All patients
      (100%) demonstrated neurological and neuroimaging abnormalities; 3 (9%) presented
      with late-onset of microcephaly. CONCLUSIONS: Children with CZS demonstrated
      visual impairment regardless of retina and/or optic nerve abnormalities. This
      finding suggests that cortical/cerebral visual impairment may be the most common
      cause of blindness identified in children with CZS.

PMID- 28450179
TI  - Amniotic membrane transplants in the pediatric population.
AB  - PURPOSE: To investigate the indications for and results of amniotic membrane
      transplantation (AMT) for the treatment of ocular disease in pediatric patients
      at a single institution. METHODS: The medical records of patients <18 years of
      age who underwent AMT for ocular disease between January 1, 2003, and September
      1, 2015, were reviewed retrospectively. Patients were determined to have reached
      a clinical endpoint if there was resolution of the ocular condition being treated
      after AMT placement, no additional surgery required for treatment of the ocular
      condition, and no active disease at most recent follow-up. RESULTS: A total of 48
      records were reviewed. Of these, 32 patients (67%) received AMT for treatment of
      ocular disease related to Stevens Johnson syndrome (SJS), 29 (94%) of whom
      reached the clinical endpoint. The remaining 16 patients (33%) underwent AMT for
      indications other than SJS, including difficult-to-treat corneal epithelial
      defects and ulcers, conjunctival reconstruction, and scarring after strabismus
      surgery. Of these, 80% reached the clinical endpoint. There were no adverse
      effects related to AMT in either group. CONCLUSIONS: In our series, AMT was used
      successfully and without complications.

PMID- 28450180
TI  - Crop Seed Size: BR Matters.

PMID- 28450176
TI  - Expanding perspectives on the significance of mitophagy in cancer.
AB  - Mitophagy is a selective mode of autophagy in which mitochondria are specifically
      targeted for degradation at the autophagolysosome. Mitophagy is activated by
      stresses such as hypoxia, nutrient deprivation, DNA damage, inflammation and
      mitochondrial membrane depolarization and plays a role in maintaining
      mitochondrial integrity and function. Defects in mitophagy lead to mitochondrial
      dysfunction that can affect metabolic reprogramming in response to stress, alter
      cell fate determination and differentiation, which in turn affects disease
      incidence and etiology, including cancer. Here, we discuss how different
      mitophagy adaptors and modulators, including Parkin, BNIP3, BNIP3L, p62/SQSTM1
      and OPTN, are regulated in response to physiological stresses and deregulated in
      cancers. Additionally, we explore how these different mitophagy control pathways
      coordinate with each other. Finally, we review new developments in understanding
      how mitophagy affects stemness, cell fate determination, inflammation and DNA
      damage responses that are relevant to understanding the role of mitophagy in
      cancer.

PMID- 28450181
TI  - WheatNet: a Genome-Scale Functional Network for Hexaploid Bread Wheat, Triticum
      aestivum.

PMID- 28450182
TI  - Cervical Papanicolaou Smears in Hematopoietic Stem Cell Transplant Recipients:
      High Prevalence of Therapy-Related Atypia during the Acute Phase.
AB  - Hematopoietic stem cell transplant (HSCT) recipients have a higher risk of
      cervical cancer. Papanicolaou (Pap) smear is the standard tool for screening
      cervical cancer, but there is limited research about the cervical cytology in
      HSCT recipients. Here, we retrospectively included adult female patients who
      underwent allogeneic or autologous HSCT at National Taiwan University Hospital
      during 2009 to 2015 and reviewed their Pap smears before and after HSCT. There
      were 248 allogeneic and 131 autologous HSCT recipients in our study. In
      allogeneic HSCT recipients, 38.7% (96 of 248) had pre-HSCT Pap smears and 17.1%
      (44 of 248) had post-HSCT Pap smears. In the autologous HSCT recipients, 35.1%
      (46 of 131) had pre-HSCT Pap smears and 13.7% (18 of 131) had post-HSCT Pap
      smears. Compared with allogeneic HSCT recipients without post-HSCT Pap smears,
      more recipients with post-HSCT Pap smears received bone marrow-derived stem cells
      (18.2% versus 4.9% respectively; P = .0077) and had longer overall survival
      (median overall survival, not reached versus 22.1 months; P < .0001). The
      abnormal rates of post-HSCT Pap smear were 13% (6 of 44) and 11% (2 of 18) in
      allogeneic and autologous recipients respectively, higher than in the general
      Taiwanese population (1.22%). Infections were rare in post-HSCT Pap smears. Of
      note, 11% (5 of 44) of post-HSCT Pap smears from allogeneic recipients showed
      therapy-related atypia, manifesting as enlarged hyperchromatic nuclei, vacuolated
      cytoplasm, and occasional tadpole-like cells. These atypical cytological features
      mimic precancerous lesions, but cervical biopsies and human papilloma virus tests
      were negative. The atypical cytological features resolved spontaneously in the
      subsequent follow-up Pap smears. On average, Pap smears with therapy-related
      atypia were sampled at day +77, significantly earlier than those without therapy
      related atypia (P = .016). Therapy-related atypia was more frequent in post-HSCT
      Pap smears sampled within 100 days after HSCT (before day +100, 4 of 5, 80%,
      versus after day +100, 1 of 39, 2.56%; P = .0002). The strong temporal
      relationship suggests these atypical cytological changes resulted from
      conditioning regimen, most likely busulfan-containing chemotherapy. No therapy
      related atypia were observed after total body irradiation or nonbusulfan
      containing chemotherapy. In conclusion, therapy-related atypia was common in post
      HSCT Pap smears sampled within 100 days after HSCT. Clinical information is
      critical for correct cytological diagnosis.

PMID- 28450184
TI  - New Prostate Cancer Biomarkers: The Search Continues.

PMID- 28450183
TI  - Hematopoietic Stem Cell Transplantation Activity in Pediatric Cancer between 2008
      and 2014 in the United States: A Center for International Blood and Marrow
      Transplant Research Report.
AB  - This Center for International Blood and Marrow Transplant Research report
      describes the use of hematopoietic stem cell transplantation (HSCT) in pediatric
      patients with cancer, 4408 undergoing allogeneic (allo) and3076 undergoing
      autologous (auto) HSCT in the United States between 2008 and 2014. In both
      settings, there was a greater proportion of boys (n = 4327; 57%), children < 10
      years of age (n = 4412; 59%), whites (n = 5787; 77%), and children with a
      performance score >= 90% at HSCT (n = 6187; 83%). Leukemia was the most common
      indication for an allo-transplant (n = 4170; 94%), and among these, acute
      lymphoblastic leukemia in second complete remission (n = 829; 20%) and acute
      myeloid leukemia in first complete remission (n = 800; 19%) werethe most common.
      The most frequently used donor relation, stem cell sources, and HLA match were
      unrelated donor (n = 2933; 67%), bone marrow (n = 2378; 54%), and matched at 8/8
      HLA antigens (n = 1098; 37%) respectively. Most allo-transplants used
      myeloablative conditioning (n = 4070; 92%) and calcineurin inhibitors and
      methotrexate (n = 2245; 51%) for acute graft-versus-host disease prophylaxis.
      Neuroblastoma was the most common primary neoplasm for an auto-transplant (n =
      1338; 44%). Tandem auto-transplants for neuroblastoma declined after 2012 (40% in
      2011, 25% in 2012, and 8% in 2014), whereas tandem auto-transplants increased for
      brain tumors (57% in 2008 and 77% in 2014). Allo-transplants from relatives other
      than HLA-identical siblings doubled between 2008 and 2014 (3% in 2008 and 6% in
      2014). These trends will be monitored in future reports of transplant practices
      in the United States.

PMID- 28450185
TI  - Prophylactic efficacy of primaquine for preventing Plasmodium falciparum and
      Plasmodium vivax parasitaemia in travelers: A meta-analysis and systematic
      review.
AB  - BACKGROUND: With increased international travel over the world the need for safe
      and effective chemoprophylaxis for malaria is as great as ever. The choice of
      regimen is difficult, as effectiveness should be weighted against potential
      adverse effects. Although, some studies have reported high prophylactic efficacy
      of primaquine, there is no comprehensive evidence comparing its prophylactic
      effectiveness as well as toxicity. To fill the gap, this systematic review and
      meta-analysis study was carried out. METHODS: Using MeSH terms, 756 records were
      detected through searching "Pubmed", "Embase","Web of Science"and "Cochrane"
      databases. From these,7 relevant full-text articles with 14 comparisons for final
      quantitative meta-analysis were included in our review. In order to make a
      comparison between the studies, Risk Ratios(RRs) and their 95% confidence
      intervals(CIs) were estimated. RESULTS: Overall,74% reduction in the incidence of
      parasitaemia by primaquine versus other prophylactic regimens was
      estimated(RRoverall = 0.26, CI 95%:0.16-0.41--RRvivax = 0.16, CI 95%:0.07-0.36-
      RRfalciparum = 0.31, CI 95%:0.18-0.55). The incidence rate ratios for adverse
      effects showed no statistically significant difference between primaquine and
      control groups (p > 0.05). CONCLUSIONS: For persons without G6PD deficiency, who
      are not pregnant, primaquine is the most effective presently available
      prophylactic for P. vivax malaria and comparable to such regimens as doxycycline,
      mefloquine and atovaquone-proguanil for the prevention of P. falciparum malaria.

PMID- 28450186
TI  - Rational malaria chemoprophylaxis - The position of primaquine.

PMID- 28450187
TI  - Nitrosoamphetamine binding to myoglobin and hemoglobin: Crystal structure of the
      H64A myoglobin-nitrosoamphetamine adduct.
AB  - N-hydroxyamphetamine (AmphNHOH) is an oxidative metabolite of amphetamine and
      methamphetamine. It is known to form inhibitory complexes upon binding to heme
      proteins. However, its interactions with myoglobin (Mb) and hemoglobin (Hb) have
      not been reported. We demonstrate that the reactions of AmphNHOH with ferric Mb
      and Hb generate the respective heme-nitrosoamphetamine derivatives characterized
      by UV-vis spectroscopy. We have determined the X-ray crystal structure of the
      H64A Mb-nitrosoamphetamine complex to 1.73 A resolution. The structure reveals
      the N-binding of the nitroso-d-amphetamine isomer, with no significant H-bonding
      interactions between the ligand and the distal pocket amino acid residues.

PMID- 28450188
TI  - Hydrogen sulfide attenuates cardiac injury in takotsubo cardiomyopathy by
      alleviating oxidative stress.
AB  - Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricular
      apical ballooning with the absence of coronary occlusion, which is an acute
      cardiac syndrome with substantial morbidity and mortality. It was reported that
      reduced endogenous hydrogen sulfide (H2S) levels may be related to various heart
      diseases. The present study investigated the mechanism by which H2S
      administration modulates and protects cardiac function in TCM rats. In order to
      establish a TCM model, Sprague Dawley (SD) rats were injected with a single dose
      of beta-adrenergic agonist isoprenaline (ISO). We found that ISO induced cardiac
      dysfunction, which was characterized by a significant decrease in left
      ventricular systolic pressure (LVSP), maximum contraction velocity (+dp/dtmax),
      maximum relaxation velocity (-dp/dtmax) and increased left ventricular end
      diastolic pressure (LVEDP). Accordingly, we found that plasma and heart tissue
      H2S levels in TCM rats decreased significantly, and cardiac cystathionine gamma
      lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) expression were
      lower. Moreover, cardiac dysfunction in TCM was associated with oxidative stress
      response and reactive oxygen species (ROS) formation. NADPH Oxidase 4 (NOX4) and
      p67 protein expressions significantly increased in TCM cardiac tissues. In
      addition, Sodium hydrosulfide (NaHS) ameliorated ISO-induced cardiac dysfunction
      and reversed ISO-induced oxidative stress. This study revealed that H2S exerted
      cardioprotective effects by reducing NADPH oxidase, which reduced ROS formation
      and prevented oxidative stress. Our study provided novel evidence that H2S is
      protective in myocardial dysfunction in TCM rats and could be a therapeutic
      target for alleviating beta-adrenergic system overstimulation-induced
      cardiovascular dysfunction.

PMID- 28450189
TI  - Unique therapeutic properties and preparation methodology of multivalent
      rituximab-lipid nanoparticles.
AB  - Therapeutic monoclonal antibodies hold great promise in the treatment of cancer
      and other diseases, but their unclear mechanism of action makes it difficult to
      identify features that will increase their efficacy. One such feature may be
      antibody valence, since enhanced therapeutic efficacies have been observed using
      multivalent, as opposed to bivalent, antibodies. For example, multivalent
      antibody-lipid nanoparticles (Ab-LNPs) containing rituximab (Rtx) or trastuzumab
      show significantly increased therapeutic activity compared to equivalent doses of
      the bivalent antibodies. To more fully understand this phenomenon, we created a
      methodology reliant on biotin-neutravidin interactions for preparing specific
      valences of Ab-LNPs that shows improvements in reproducibility, preparation time
      and overall yield of coupled Ab (up to 80%). We subsequently prepared a series of
      valences of Rtx-LNPs to examine binding characteristics to CD20+ lymphoma cells,
      distribution of Rtx-LNPs on the cell surface, modulation of CD20 expression,
      cytotoxicity of the constructs and ability of the different valences to directly
      induce apoptosis. As the valence of Rtx-LNP was increased, the amount of Rtx
      bound to cells increased up to ~10-fold higher compared to bivalent Rtx. Although
      more Rtx was bound to cells, there were also surprising increases in the levels
      of unbound CD20. This suggested the formation of Rtx-enriched microdomains that
      were confirmed using confocal fluorescence laser-scanning microscopy. Multivalent
      Rtx-LNPs were significantly more cytotoxic than Rtx; for equivalent doses of
      drug, Rtx-LNPs elicited apoptosis in two lymphoma cell lines in a valence
      dependent manner up to levels that were 14-fold higher than bivalent Rtx. It is
      suggested that CD20-enriched microdomains may play a role in the mechanism of
      action of Rtx. This new preparation methodology can be used in future studies
      evaluating the mechanism of action of multivalent Ab-LNPs prepared with Rtx or
      other therapeutic Abs.

PMID- 28450190
TI  - Differentiation chronic post traumatic stress disorder patients from healthy
      subjects using objective and subjective sleep-related parameters.
AB  - Sleep disturbance is common in chronic post-traumatic stress disorder (PTSD).
      However, prior work has demonstrated that there are inconsistencies between
      subjective and objective assessments of sleep disturbance in PTSD. Therefore, we
      investigated whether subjective or objective sleep assessment has greater
      clinical utility to differentiate PTSD patients from healthy subjects. Further,
      we evaluated whether the combination of subjective and objective methods improves
      the accuracy of classification into patient versus healthy groups, which has
      important diagnostic implications. We recruited 32 chronic war-induced PTSD
      patients and 32 age- and gender-matched healthy subjects to participate in this
      study. Subjective (i.e. from three self-reported sleep questionnaires) and
      objective sleep-related data (i.e. from actigraphy scores) were collected from
      each participant. Subjective, objective, and combined (subjective and objective)
      sleep data were then analyzed using support vector machine classification. The
      classification accuracy, sensitivity, and specificity for subjective variables
      were 89.2%, 89.3%, and 89%, respectively. The classification accuracy,
      sensitivity, and specificity for objective variables were 65%, 62.3%, and 67.8%,
      respectively. The classification accuracy, sensitivity, and specificity for the
      aggregate variables (combination of subjective and objective variables) were
      91.6%, 93.0%, and 90.3%, respectively. Our findings indicate that classification
      accuracy using subjective measurements is superior to objective measurements and
      the combination of both assessments appears to improve the classification
      accuracy for differentiating PTSD patients from healthy individuals.

PMID- 28450191
TI  - Targeting neuronal nitric oxide synthase by a cell penetrating peptide Tat
      LK15/siRNA bioconjugate.
AB  - We developed a cell penetrating peptide (CPP) Tat-LK15, as a siRNA carrier to
      target nNOS. The feasibility, stability, efficiency and selectivity of this
      peptide-siRNA complex were evaluated in rat neuronal cells. We also compared the
      new method with conventional siRNA carrier LipofectamineTM. It was found that the
      CPP Tat-LK15 effectively and specifically delivered nNOS-siRNA into Rat retinal
      ganglia (RGC-5) cells and silenced the expression of nNOS. The CPP Tat-LK15 can
      conjugate with siRNA to form stable complex at a ratio of 2:1 (peptide/siRNA,
      w/w), which maintained stable in serum for as long as 4h. The CPP Tat-LK15 was
      low-toxicity to cells, as the apoptosis rate of treat cells was not increased
      significantly when the used peptide lower than 10MUg/mL. Moreover, the cellular
      uptake of nNOS siRNA by Rat Neurons-dorsal spinal cord (RNdsc) cells was also
      significantly more than naked siRNA by RNdsc cells. The CPP Tat-LK15 was an
      efficient and stable, and non-cytotoxic siRNA delivery to neurons and effectively
      silenced the nNOS expression. The CPP Tat-LK15 mediated siRNA delivery was a
      potential tool to treat neuropathic diseases involving NO or nNOS neurotoxic
      cascades.

PMID- 28450192
TI  - Do the accelerating actions of tianeptine and l-arginine on cortical spreading
      depression interact? An electrophysiological analysis in young and adult rats.
AB  - In the rat, we previously demonstrated that serotonin-enhancing drugs impair
      cortical spreading depression (CSD) and that l-arginine (arginine) treatment
      enhances CSD. Here, we investigated the interaction between topical application
      of the serotonin uptake enhancer tianeptine and systemic arginine administration
      on CSD. From postnatal day 7-28, female Wistar rats (n=40) received by gavage
      300mg/Kg/day arginine (n=20) or water (n=20). Half of the arginine- or water
      treated rats underwent CSD recording at 30-40days of age (young), while the other
      half was recorded at 90-120days (adult). Following baseline recording (four
      episodes of CSD), we applied tianeptine solution (10mg/ml) to a rectangular
      portion of the intact dura mater for 10-min and then elicited CSD. This procedure
      was repeated three times. Compared to baseline values, CSD velocities and
      amplitudes following tianeptine application increased, and CSD duration decreased
      significantly (p<0.05) in both young and adult rats, regardless of treatment
      group. CSD acceleration caused by systemic treatment with arginine is in
      agreement with previous findings. Topical cortical application of tianeptine
      replicated the effect of systemic application, suggesting a cortically based
      mechanism for tianeptine's action. However, the absence of interaction between
      arginine and tianeptine treatments suggests that they probably act through
      separate mechanisms.

PMID- 28450193
TI  - Developing standardized corticosteroid treatment for Duchenne muscular dystrophy.
AB  - Despite corticosteroids being the only treatment documented to improve strength
      and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid
      prescription is inconsistent and in some countries, corticosteroids are not
      prescribed. We are conducting a clinical trial that (1) compares the 3 most
      frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD
      complications; and (3) standardizes prevention of corticosteroid side effects.
      Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who
      are randomly assigned to one of three regimens: daily prednisone; daily
      deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed
      for a minimum of 3years to assess the relative effectiveness and adverse event
      profiles of the different regimens. The primary outcome is a 3-dimensional
      variable consisting of log-transformed time to rise from the floor, forced vital
      capacity, and subject/parent satisfaction with treatment, each averaged over all
      post-baseline visits. The study protocol includes evidence- and consensus-based
      treatment of DMD complications and of corticosteroid side effects. This study
      seeks to establish a standard corticosteroid regimen for DMD. Since all new
      interventions for DMD are being developed as add-on therapies to corticosteroids,
      defining the optimum regimen is of importance for all new treatments.

PMID- 28450195
TI  - Evaluation of the eazyplex MRSA assay for the rapid detection of Staphylococcus
      aureus in pleural and synovial fluid.
AB  - OBJECTIVE: Loop-mediated isothermal amplification (LAMP) is a simple and
      sensitive technique for rapid microbiological diagnosis. The aim of this study
      was to evaluate the analytical and diagnostic performance of the LAMP eazyplex
      MRSA test for the direct detection and differentiation of methicillin-susceptible
      (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) in synovial/pleural
      fluid. METHODS: Analytical validation included the determination of the limit of
      detection (LoD) and analytical specificity of the eazyplex MRSA test. A
      diagnostic evaluation of the eazyplex test against bacterial culture was
      performed on routine pleural/synovial samples collected prospectively from
      patients aged less than 18 years with complicated pneumonia with empyema or
      arthritis admitted to the Children's Hospital Sant Joan de Deu in Barcelona,
      Spain, between April 2015 and May 2016. RESULTS: The new system appropriately
      detected a quality control panel of clinical samples with DNA of MSSA, MRSA, and
      other pathogens. The LoD was established at 6.4*103 CFU/ml for S. aureus and
      1.0*104 CFU/ml for MRSA. Diagnostic validation of the eazyplex MRSA assay was
      performed on 51 prospective clinical invasive samples, resulting in sensitivity
      and specificity values of 83.3% and 97.8%, respectively, for S. aureus detection.
      The mean turnaround time was 70min. CONCLUSIONS: The eazyplex MRSA assay was
      found to be a useful test for the rapid detection of S. aureus in invasive
      samples such as pleural/synovial fluid.

PMID- 28450194
TI  - Design and baseline data from a PCORI-funded randomized controlled trial of
      family-centered tailoring of diabetes self-management resources.
AB  - : This article describes the methodology, recruitment, participant
      characteristics, and sustained, intensive stakeholder engagement for Project ACE
      (Achieving control, Connecting resources, Empowering families). Project ACE is a
      randomized controlled trial of children and youth ages 8-16 with type 1 diabetes
      evaluating the impact of tailored self-management resources on hemoglobin A1c
      (A1c) and quality of life (QOL). Despite strong evidence that controlling A1c
      reduces long-term complications, <25% of US youth with type 1 diabetes meet A1c
      targets. Many interventions are efficacious in improving A1c and QOL for these
      youth, whose families often struggle with the substantial demands of the
      treatment regimen. However, most such interventions are ineffective in the real
      world due to lack of uptake by families and limited healthcare system resources.
      Project ACE is a multi-site trial designed to improve diabetes outcomes by
      tailoring existing, evidence-based interventions to meet families' needs and
      preferences. We hypothesize that this family-centered approach will result in
      better A1c and QOL than usual care. Project ACE has recruited and randomized 214
      eligible 8-16year old youth and their parents. The 9-month intervention consisted
      of 4 group sessions tailored to families' self-management barriers as identified
      by a validated instrument. Outcomes including A1c and QOL for parents and youth
      will be assessed for 1year after the intervention. Stakeholder engagement was
      used to enhance this trial's recruitment, retention and integration into routine
      clinical care. Findings will inform implementation and dissemination of family
      centered approaches to address self-management barriers. TRIAL REGISTRATION
      NUMBER: NCT02024750 Trial Registrar: Clinicaltrials.gov,
      https://clinicaltrials.gov/ct2/show/NCT02024750.

PMID- 28450196
TI  - Receipt of thyroid hormone deficiency treatment and risk of herpes zoster.
AB  - OBJECTIVE: Thyroid hormone (TH) has been suggested to control herpes virus gene
      expression and replication in neurons via epigenetics through its nuclear
      receptors. It has previously been shown that patients with hypothyroidism are
      predisposed to herpes zoster (HZ), suggesting that the TH deficiency may be a
      risk factor for varicella zoster virus (VZV) reactivation. The aim of this study
      was to test the hypothesis that TH treatment will ameliorate the complication of
      HZ. METHODS: This study investigated the hypothesis by enquiring into a
      comprehensive medical database at Kaiser Permanente Southern California (KPSC) to
      verify whether patients taking TH medication experience a reduction in HZ
      occurrence. RESULTS: It was shown by Kaplan-Meier analysis that hypothyroidism
      patients taking TH medicines had a lower risk of HZ. The fully adjusted analysis
      indicated that patients receiving medication for the treatment of TH deficiency
      exhibited a reduced risk of HZ (hazard ratio 0.60, 95% confidence interval 0.51
      0.71). This lower risk of HZ was significant in all age groups except the 18-39
      years cohort. In addition, female patients taking TH treatment exhibited a lower
      risk than their male counterparts. CONCLUSIONS: Together these findings support
      the hypothesis that a constant level of TH will provide a degree of protection
      from contracting HZ. More studies are underway to evaluate the laboratory data
      for an analysis of hormonal effects on individuals.

PMID- 28450197
TI  - A new paradigm in pneumococcal conjugate vaccination: moving from individual to
      herd protection.

PMID- 28450198
TI  - Are antibiotic-resistant pathogens more common in subsequent episodes of diabetic
      foot infection?
AB  - BACKGROUND: After antibiotic therapy of an initial diabetic foot infection (DFI),
      pathogens isolated from subsequent episodes might become more resistant to
      commonly prescribed antibiotics. If so, this might require a modification of the
      current recommendations for the selection of empiric antibiotic therapy. This
      study investigated whether the Infectious Diseases Society of America (IDSA) DFI
      guideline recommendations should be modified based on the number of past DFI
      episodes. METHODS: This was a single-centre retrospective cohort survey of DFI
      patients seen during the years 2010 to 2016. RESULTS: A total 1018 episodes of
      DFI in 482 adult patients were identified. These patients were followed-up for a
      median of 3.3 years after the first DFI episode. The total number of episodes was
      2257 and the median interval between recurrent episodes was 7.6 months. Among the
      recurrent DFIs, the causative pathogens were the same as in the previous episode
      in only 43% of cases (158/365). Staphylococcus aureus was the predominant
      pathogen in all episodes (range 1 to 13 episodes) and was not more prevalent with
      the increasing number of episodes. DFIs were treated with systemic antibiotics
      for a median duration of 20 days (interquartile range 11-35 days). Overall, there
      was no significant increase in the incidence of antibiotic resistance to
      methicillin, rifampicin, clindamycin, or ciprofloxacin over the episodes
      (Pearson's Chi-square test p-values of 0.76, 1.00, 0.06, and 0.46, respectively;
      corresponding p-values for trend of 0.21, 0.27, 0.38, and 0.08, respectively).
      CONCLUSIONS: After the successful treatment of a DFI, recurrent episodes are
      frequent. A history of a previous DFI episode did not predict a greater
      likelihood of any antibiotic-resistant isolate in subsequent episodes. Thus,
      broadening the spectrum of empiric antibiotic therapy for recurrent episodes of
      DFI does not appear necessary.

PMID- 28450199
TI  - Severe glandular tularemia in a patient treated with anti-tumour necrosis factor
      for psoriatic arthritis.
AB  - A case of severe glandular tularemia in a patient receiving anti-tumour necrosis
      factor (TNF) therapy is reported here. The patient required prolonged treatment
      with doxycycline-ciprofloxacin due to early relapse after ciprofloxacin was
      stopped. Tularemia may have a more severe course in patients receiving anti-TNF.
      This may thus be an indication for more aggressive treatment.

PMID- 28450200
TI  - Aerosolized tobramycin for Pseudomonas aeruginosa ventilator-associated pneumonia
      in patients with acute respiratory distress syndrome.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) due to Pseudomonas aeruginosa
      has a high mortality and recurrence rate, especially in patients with acute
      respiratory distress syndrome (ARDS). Therefore, new therapeutic strategies
      against severe pneumonia are needed. This study evaluated the efficacy of
      aerosolized tobramycin for P. aeruginosa VAP in ARDS patients. METHODS: A
      retrospective analysis was performed on patients who developed VAP caused by P.
      aeruginosa during the course of ARDS at the intensive care unit (ICU) of Kumamoto
      University Hospital. Aerosolized tobramycin inhalation solution (TIS) 240 mg was
      administered daily for 14 days in addition to systemic antibiotics. RESULTS: A
      total of 44 patients (TIS group, n = 22; control group, n = 22) were included in
      the analysis. No significant differences were found between the two groups in
      terms of clinical characteristics, including acute physiology and chronic health
      evaluation II score upon ICU admission. The TIS group had significantly lower
      recurrence of P. aeruginosa VAP (22.7% vs. 52.4%, P = 0.04) and ICU mortality
      (22.7% vs. 63.6%, P < 0.01) than the control group. Bacterial concentration in
      tracheal aspirate (mean log 10 cfu/mL +/- SD on days 2-5: 1.2 +/- 1.3 vs. 5.0 +/-
      2.3, P < 0.01) decreased more rapidly and markedly in the TIS group compared with
      the control group. CONCLUSION: Aerosolized tobramycin was an effective
      therapeutic strategy for P. aeruginosa VAP patients with ARDS.

PMID- 28450201
TI  - Re: Pak et al.: Utilization Trends and Short-term Outcomes of Robotic Versus Open
      Radical Cystectomy for Bladder Cancer (Urology 2017;103:117-123) and Borza et
      al.: No Differences in Population-based Readmissions After Open and Robotic
      assisted Cystectomy: Implications for Post-discharge Care (Urology 2017;104:77
      83).

PMID- 28450202
TI  - Minimally Invasive Inguinal Lymphadenectomy in the Management of Penile
      Carcinoma.
AB  - OBJECTIVE: To report and analyze the outcomes of endoscopic inguinal lymph node
      dissection (E-ILND), inclusive of video endoscopic ILND (VEIL) and robotic
      assisted ILND (RAIL) approaches, in the largest reported series to date.
      MATERIALS AND METHODS: We retrospectively identified men with penile cancer who
      underwent E-ILND. Nodal resection volume, perioperative parameters, and
      postoperative complications were assessed and analyzed. A subset analysis of
      complications by tumor and operative characteristics was performed to determine
      the impact of these variables on complication rates. RESULTS: A total of 34 E
      ILND, comprising 7 VEIL and 27 RAIL limbs, were performed. Median nodal yield was
      10.0 (interquartile range [IQR] 6.0-12.5) in all E-ILND limbs and 8.0 (IQR 13.0
      23.0) in RAIL limbs. Median length of stay was 1 day (range 1-3) following E-ILND
      and RAIL procedures. The saphenous vein was spared in 57% (4/7) of VEIL and 100%
      (27/27) of RAIL limbs. Postoperative complications occurred in 33% (6/18) of E
      ILND, including 21% (3/14) of RAIL patients. Median follow-up was 5.5 months (IQR
      3.0-10.8), during which time 3 patients developed regional or distant metastases
      at a median duration of 1.7 months (IQR 0.9-3.9). CONCLUSION: E-ILND is feasible
      from a technical standpoint, and our results demonstrate that lymph node counts
      are comparable with an open approach. Importantly, E-ILND has the potential to
      reduce complication rates and time to convalescence when compared with open ILND.

PMID- 28450203
TI  - Processing of gaze direction within the N170/M170 time window: A combined EEG/MEG
      study.
AB  - Gaze direction is an important social signal for human beings. Beside the role of
      gaze in attention orienting, direct gaze (that is, gaze directed toward an
      observer) is a highly relevant biological stimulus that elicits attention capture
      and increases face encoding. Brain imaging studies have emphasized the role of
      the superior temporal sulcus (STS) in the coding of gaze direction and in the
      integration of gaze and head cues of social attention. The dynamics of the
      processing and integration of these cues remains, however, unclear. In order to
      address this question, we used deviated and frontal faces with averted and direct
      gaze in a combined electro- and magneto- encephalography (EEG-MEG) study. We
      showed distinct effects of gaze direction on the N170 and M170 responses. There
      was an interaction between gaze direction and head orientation between 134 and
      162ms in MEG and a main effect of gaze direction between 171 and 186ms in EEG.
      These effects involved the posterior and anterior regions of the STS
      respectively. Both effects also emphasized the sensitivity to direct gaze. These
      data highlight the central role of the STS in gaze processing.

PMID- 28450204
TI  - Early sensitivity of left perisylvian cortex to relationality in nouns and verbs.
AB  - The ability to track the relationality of concepts, i.e., their capacity to
      encode a relationship between entities, is one of the core semantic abilities
      humans possess. In language processing, we systematically leverage this ability
      when computing verbal argument structure, in order to link participants to the
      events they participate in. Previous work has converged on a large region of left
      posterior perisylvian cortex as a locus for such processing, but the wide range
      of experimental stimuli and manipulations has yielded an unclear picture of the
      region's exact role(s). Importantly, there is a tendency for effects of
      relationality in single-word studies to localize to posterior temporo-parietal
      cortex, while argument structure effects in sentences appear in left superior
      temporal cortex. To characterize these sensitivities, we designed two MEG
      experiments that cross the factors relationality and eventivity. The first used
      minimal noun phrases and tested for an effect of semantic composition, while the
      second employed full sentences and a manipulation of grammatical category. The
      former identified a region of the left inferior parietal lobe sensitive to
      relationality, but not eventivity or combination, beginning at 170ms. The latter
      revealed a similarly-timed effect of relationality in left mid-superior temporal
      cortex, independent of eventivity and category. The results suggest that i)
      multiple sub-regions of perisylvian cortex are sensitive to the relationality
      carried by concepts even in the absence of arguments, ii) linguistic context
      modulates the locus of this sensitivity, consistent with prior studies, and iii)
      relationality information is accessed early - before 200ms - regardless of the
      concept's event status or syntactic category.

PMID- 28450205
TI  - Nucleic acid combinations: A new frontier for cancer treatment.
AB  - The emerging molecular understanding of cancer cell behavior is leading to
      increasing possibilities to control unchecked cell growth and metastasis. On the
      other hand, development of multifunctional drug carriers at the 'nano'-scale is
      providing exciting new therapeutic strategies in clinical management of cancer
      beyond the conventional cytotoxic drugs. A new frontier in this regard is the
      combinational use of complementary agents based on nucleic acids to overcome the
      limitations of conventional therapy. The existence of tightly-integrated cross
      talk through multiple signaling and effector pathways have been appreciated for
      some time, and the plasticity of such a network to overcome one-dimensional
      intervention is stimulating development of combinational therapy. The objective
      of this review is to underline the cutting edge technologies and opportunities
      employed in combination cancer therapy using nucleic acids therapeutics for
      successful clinical translation. Here, we provide a detailed analysis of the
      multifunctional carriers designed for different types of payloads, surveying the
      biomaterials used to construct the functional carriers. We then provide effective
      nucleic acid combinations employed to obtain more comprehensive outcomes,
      highlighting the critical factors involved in successful therapy. We conclude
      with an authors' perspective on the future of combinational therapy using nucleic
      acid therapeutics, articulating the main challenges to advance this promising
      approach to the clinical realm.

PMID- 28450206
TI  - Development of a discriminative biphasic in vitro dissolution test and
      correlation with in vivo pharmacokinetic studies for differently formulated
      racecadotril granules.
AB  - The purpose of this study was to discriminate the release behavior from three
      differently formulated racecadotril (BCS II) granules and to establish an in
      vitro-in vivo correlation. Three granule formulations of the lipophilic drug were
      prepared with equivalent composition but prepared with different manufacturing
      processes (dry granulation, wet granulation with or without binder). In vitro
      release of the three granules was investigated using a biphasic dissolution
      system (phosphate buffer pH6.8 and octanol) and compared to the conventional
      single phase USP II dissolution test performed under sink and non-sink
      conditions. In vivo studies with each granule formulation were performed in rats.
      Interestingly, the granule formulations exhibited pronouncedly different behavior
      in the different dissolution systems depending on different wetting and
      dissolution conditions. Single phase USP II dissolution tests lacked
      discrimination. In contrast, remarkable discrimination between the granule
      formulations was observed in the octanol phase of biphasic dissolution system
      with a rank order of release from granules prepared by wet granulation with
      binder>wet granulation without binder>dry granulation. This release order
      correlated well with the wettability of these granules. An excellent correlation
      was also established between in vitro release in the octanol phase of the
      biphasic test and in vivo data (R2=0.999). Compared to conventional dissolution
      methods, the biphasic method provides great potential to discriminate between
      only minor formulation and process changes within the same dosage form for poorly
      soluble drugs.

PMID- 28450207
TI  - Drug release studies from lipid nanoparticles in physiological media by a new DSC
      method.
AB  - Lipid nanoparticles are an interesting parenteral delivery system for poorly
      water-soluble drugs. In order to approach physiological conditions when
      conducting release studies from such systems the release media should
      preferentially contain lipophilic acceptor compartments such as lipoproteins or
      other colloidal lipophilic components. In practice, drug release studies under
      such close to physiological conditions may be complicated by the small size of
      lipid nanoparticles, which is in the same range as that of the potential acceptor
      particles. This study describes a novel differential scanning calorimetry (DSC)
      method for drug release measurements which works without separation of donor and
      acceptor particles. The technique is based on measuring the crystallization
      temperature of trimyristin nanoparticles by DSC. The crystallization temperature
      of the nanoparticles decreases proportionally with the amount of active
      ingredient incorporated and thus increases as a result of drug release. Liquid
      trimyristin nanoparticles loaded with fenofibrate, orlistat, tocopherol acetate
      and ubidecarenone were studied in three different release media with increasing
      complexity and comparability to physiological conditions: a rapeseed oil
      nanoemulsion, porcine serum and porcine blood. Using the new method, a
      correlation between release behavior and drug lipophilicity was observed: the
      higher the logP value of the drug, the slower the release. The extent of drug
      release was influenced by partition equilibrium as indicated by increased drug
      release in the rapeseed oil nanoemulsion compared to porcine serum and blood.

PMID- 28450208
TI  - Modelling dengue fever risk in the State of Yucatan, Mexico using regional-scale
      satellite-derived sea surface temperature.
AB  - Accurately predicting vector-borne diseases, such as dengue fever, is essential
      for communities worldwide. Changes in environmental parameters such as
      precipitation, air temperature, and humidity are known to influence dengue fever
      dynamics. Furthermore, previous studies have shown how oceanographic variables,
      such as El Nino Southern Oscillation (ENSO)-related sea surface temperature from
      the Pacific Ocean, influences dengue fever in the Americas. However, literature
      is lacking on the use of regional-scale satellite-derived sea surface temperature
      (SST) to assess its relationship with dengue fever in coastal areas. Data on
      confirmed dengue cases, demographics, precipitation, and air temperature were
      collected. Incidence of weekly dengue cases was examined. Stepwise multiple
      regression analyses (AIC model selection) were used to assess which environmental
      variables best explained increased dengue incidence rates. SST, minimum air
      temperature, precipitation, and humidity substantially explained 42% of the
      observed variation (r2=0.42). Infectious diseases are characterized by the
      influence of past cases on current cases and results show that previous dengue
      cases alone explained 89% of the variation. Ordinary least-squares analyses
      showed a positive trend of 0.20+/-0.03 degrees C in SST from 2006 to 2015. An
      important element of this study is to help develop strategic recommendations for
      public health officials in Mexico by providing a simple early warning capability
      for dengue incidence.

PMID- 28450209
TI  - A new Myxidium species (Myxozoa: Myxosporea) infecting the gallbladder of the
      turtle Podocnemis unifilis (Testudines: Podocnemididae) from Peruvian Amazon.
AB  - A new myxosporean species, Myxidium peruviensis n. sp., is described parasitizing
      the gall bladder of the yellow-spotted river turtle Podocnemis unifilis kept in
      captivity in an Amazonian Peruvian turtle rescue unit in the city of Iquitos,
      State of Loreto, Peru. The parasite was found in four of ten (40%) P. unifilis
      examined. The new species was characterized based on morphological and molecular
      phylogeny analyses. SSU rDNA sequence of the spores of M. peruviensis n. sp.
      resulted in 1876 nucleotides and this sequence did no match any of the Myxozoa
      available in the GenBank. Phylogenetic analysis identified the new species as a
      sister species of Myxidium turturibus, the unique Myxidium species described in a
      Neotropical turtle. Nevertheless, the SSU rDNA sequences of the new species and
      M. turturibus have only a 91.5% similarity. This is the first description and
      molecular study of a Myxozoa in a reptile from Peru. Considering the status of P.
      unifilis as vulnerable species, the infection by Myxidium parasites is emphasized
      as possible disease impeller, representing menace to the turtle conservation.

PMID- 28450210
TI  - Emerging variant of genotype XIII Newcastle disease virus from Northeast India.
AB  - Northeast India with its rich and diverse avifauna acts as a hotbed for emerging
      virulent Newcastle disease virus (NDV) strains. The present work describes the
      molecular and pathogenic characterization of NDV strain isolated from Pandu,
      Assam, India. Clinicopathological and genetic analysis showed the virulent nature
      of NDV strain Pandu. On molecular phylogenetic and evolutionary distance
      analysis, the NDV strain Pandu formed a distinct clade within the genotype XIII
      of class II NDV, suggesting a new sub-genotype XIIIc. The accumulation of
      mutations in the NDV strain Pandu makes it divergent enough to be considered as a
      new sub-genotype. The proposed NDV sub-genotype XIIIc consists of strains
      recently reported from eastern and northeastern India.

PMID- 28450211
TI  - Sero-prevalence of Taenia spp. infections in cattle and pigs in rural farming
      communities in Free State and Gauteng provinces, South Africa.
AB  - The aim of this study was to determine sero-prevalence of bovine and porcine
      cysticercosis in cattle and pigs in rural farming communities in Free State and
      Gauteng Provinces, Republic of South Africa. Blood samples were collected for a
      period of twelve months from live cattle (n=1315; 1159) and pigs (n=436; 240) and
      the serum extracted and stored before analysis by a monoclonal antibody based
      (HP10) antigen detection ELISA. Results revealed a generally high sero-prevalence
      and wide distribution throughout the two provinces with Free State having a
      higher sero-prevalence in both cattle and pigs (23% and 34%) than Gauteng
      province (15% and 14%). Consumption of infected meat that is either not
      inspected/missed at meat inspection; poor livestock management practices and
      limited sanitation in rural communities might have contributed to the occurrence
      of Taenia spp. infections in the two provinces. It is therefore, recommended that
      cysticercosis status of animals be established before slaughter. This would
      assist in ensuring that infected animals are not slaughtered for human
      consumption or zoonosis preventive measures are taken. Furthermore, public
      awareness programs on life cycles of T. saginata, T. solium and T. hydatigena and
      the use of more sensitive diagnostic tools are recommended as part of effective
      control strategies against taeniid infections.

PMID- 28450212
TI  - Comment on: Diagnosis of intestinal parasites in a rural community of Venezuela:
      Advantages and disadvantages of using microscopy or RT-PCR.

PMID- 28450213
TI  - Isolation, characterization, virulence and immunogenicity testing of field
      isolates of Pasteurella multocida, Staphylococcus aureus, and Streptococcus
      agalactiae in laboratory settings.
AB  - : The present study was designed to investigate isolation, characterization,
      virulence and immunogenicity testing of field isolates of Pasteurella multocida,
      Staphylococcus aureus, and Streptococcus agalactiae in rabbits and mice. Isolates
      of P. multocida, S. aureus and Str. agalactiae recovered from field cases of
      Hemorragic septicemia and mastitis were scrutinized for virulence/pathogenicity
      and immunogenicity. Mouse LD50 of P. multocida showed that P. multocida isolate
      No.1 was more virulent than isolates No. 2 and 3. Virulence of isolate No.1S.
      aureus and Str. agalactiae revealed that 100, 80% rabbits died within 18h of
      inoculation. Seven-digit numerical profiles of these 4 isolates with API(r) Staph
      test strips isolates, No.1 (6736153) showed good identification (S. aureus
      id=90.3%). Indirect ELISA-based serum antibody titers to P. multocida isolate
      No.1, S. aureus No.1, Str. agalactiae, isolate No.1 elicited high antibody titers
      1.9, 1.23, 1.12 respectively. CONCLUSION: All the pathogens of Isolate No. 1 (P.
      multocida, S. aureus Str. agalactiae), were high antibody than others isolates.

PMID- 28450214
TI  - Omics analysis of human bone to identify genes and molecular networks regulating
      skeletal remodeling in health and disease.
AB  - The skeleton is a metabolically active organ throughout life where specific bone
      cell activity and paracrine/endocrine factors regulate its morphogenesis and
      remodeling. In recent years, an increasing number of reports have used multi
      omics technologies to characterize subsets of bone biological molecular networks.
      The skeleton is affected by primary and secondary disease, lifestyle and many
      drugs. Therefore, to obtain relevant and reliable data from well characterized
      patient and control cohorts are vital. Here we provide a brief overview of omics
      studies performed on human bone, of which our own studies performed on trans
      iliacal bone biopsies from postmenopausal women with osteoporosis (OP) and
      healthy controls are among the first and largest. Most other studies have been
      performed on smaller groups of patients, undergoing hip replacement for
      osteoarthritis (OA) or fracture, and without healthy controls. The major findings
      emerging from the combined studies are: 1. Unstressed and stressed bone show
      profoundly different gene expression reflecting differences in bone turnover and
      remodeling and 2. Omics analyses comparing healthy/OP and control/OA cohorts
      reveal characteristic changes in transcriptomics, epigenomics (DNA methylation),
      proteomics and metabolomics. These studies, together with genome-wide association
      studies, in vitro observations and transgenic animal models have identified a
      number of genes and gene products that act via Wnt and other signaling systems
      and are highly associated to bone density and fracture. Future challenge is to
      understand the functional interactions between bone-related molecular networks
      and their significance in OP and OA pathogenesis, and also how the genomic
      architecture is affected in health and disease.

PMID- 28450215
TI  - Effect of parity on bone mineral density: A systematic review and meta-analysis.
AB  - INTRODUCTION: Parity has been suggested as a possible factor affecting bone
      health in women. However, study results on its association with bone mineral
      density are conflicting. METHODS: PubMed, EMBASE, the Cochrane Library, and
      Korean online databases were searched using the terms "parity" and "bone mineral
      density", in May 2016. Two independent reviewers extracted the mean and standard
      deviation of bone mineral density measurements of the femoral neck, spine, and
      total hip in nulliparous and parous healthy women. RESULTS: Among the initial
      10,146 studies, 10 articles comprising 24,771 women met the inclusion criteria.
      The overall effect of parity on bone mineral density was positive (mean
      difference=5.97mg/cm2; 95% CI 2.37 to 9.57; P=0.001). The effect appears site
      specific as parity was not significantly associated with the bone mineral density
      of the femoral neck (P=0.09) and lumbar spine (P=0.17), but parous women had
      significantly higher bone mineral density of the total hip compared to
      nulliparous women (mean difference=5.98mg/cm2; 95% CI 1.72 to 10.24; P=0.006). No
      obvious heterogeneity existed among the included studies (femoral neck I2=0%;
      spine I2=31%; total hip I2=0%). CONCLUSION: Parity has a positive effect on bone
      in healthy, community-dwelling women and its effect appears site-specific.

PMID- 28450216
TI  - Effects of End-of-Life Discussions on the Mental Health of Bereaved Family
      Members and Quality of Patient Death and Care.
AB  - CONTEXT: End-of-life discussions are crucial for providing appropriate care to
      patients with advanced cancer at the end of their lives. OBJECTIVES: The
      objective of this study was to explore associations between end-of-life
      discussions and bereaved families' depression and complicated grief and the
      quality of patient death and end-of-life care. METHODS: A nationwide
      questionnaire survey of bereaved family members was conducted between May and
      July 2014. A total of 13,711 bereaved family members of cancer patients who were
      cared for by specialist palliative care services at 75 institutions throughout
      Japan and died before January 2014 participated. We evaluated the prevalence of
      depression (defined as the Patient Health Questionnaire-9 >= 10) and complicated
      grief (defined as the Brief Grief Questionnaire >= 8) in bereaved family members.
      Moreover, we evaluated the quality of death and end-of-life care with the Good
      Death Inventory and the Care Evaluation Scale, respectively. RESULTS: A total of
      9123 questionnaires were returned (response rate 67%), and 80.6% of the
      respondents reported that they had end-of-life discussions. After propensity
      score-weighted adjustment, the results showed that bereaved family members who
      had end-of-life discussions had a lower frequently of depression (17.3% vs.
      21.6%; P < 0.001) and complicated grief (13.7% vs. 15.9%; P = 0.03). End-of-life
      discussions were associated with better quality of death (the Good Death
      Inventory score, 47.2 +/- 8.5 vs. 46.1 +/- 9.4; P < 0.001) and end-of-life care
      (the Care Evaluation Scale score, 84.1 +/- 11.4 vs. 78.9 +/- 14.3; P < 0.001).
      CONCLUSION: End-of-life discussions may contribute to reducing depression and
      complicated grief in bereaved family members and enable patients to experience
      quality end-of-life care and a good death.

PMID- 28450217
TI  - Hospice Enrollment After Referral to Community-Based, Specialist Palliative Care:
      Impact of Telephonic Outreach.
AB  - CONTEXT: In the U.S., palliative care programs improve access to hospice through
      enhanced communication and efficiencies in hospice eligibility review and
      enrollment. For community-based programs, this task may begin with telephone
      contact. OBJECTIVES: To evaluate the incidence and predictors of hospice
      enrollment following telephonic outreach by a nurse after referral to a community
      based, specialist palliative care program. METHODS: During 2012-2014, 299
      consecutive patients who were referred to a palliative care program and
      subsequently enrolled in hospice provided electronic health record data for a
      retrospective cohort study. Those who elected hospice after telephonic outreach
      and before the first palliative care home visit, were compared with those who
      enrolled in hospice after palliative care visits began, using both bivariate and
      multivariate analyses. RESULTS: Mean (SD) age was 74.1 (18.7) years; 60.2% were
      women, 44.4% were White, 22.5% were Hispanic, 20.9% were Black, and 9.6% were
      Asian. In total, 177 patients (59.2%) elected hospice following telephonic
      outreach and 122 (40.8%) enrolled after home visits began. The former group
      received a mean of 4.5 calls (median = 3.0) before hospice election. In
      multivariate analysis, hospice enrollment following telephonic outreach alone was
      associated with hospital or nursing home referral, not married status, and poor
      performance status (all P < 0.05). CONCLUSION: More than half of patients
      electing hospice after referral to a palliative care program did so following
      telephonic outreach alone. Both sociodemographic and clinical characteristics
      predicted this outcome. Palliative care programs can improve hospice access
      through initial telephonic outreach by trained professionals.

PMID- 28450218
TI  - Financial Incentives to Increase Advance Care Planning Among Medicaid
      Beneficiaries: Lessons Learned From Two Pragmatic Randomized Trials.
AB  - CONTEXT: Medicaid populations have low rates of advance care planning (ACP).
      Potential policy interventions include financial incentives. OBJECTIVE: To test
      the effectiveness of patient plus provider financial incentive compared with
      provider financial incentive alone for increasing ACP discussions among Medicaid
      patients. METHODS: Between April 2014 and July 2015, we conducted two sequential
      assessor-blinded pragmatic randomized trials in a health plan that pays primary
      care providers (PCPs) $100 to discuss ACP: 1) a parallel cluster trial (provider
      delivered patient incentive) and 2) an individual-level trial (mail-delivered
      patient incentive). Control and intervention arms included encouragement to
      complete ACP, instructions for using an online ACP tool, and (in the intervention
      arm) $50 for completing the online ACP tool and a small probability of $1000
      (i.e., lottery) for discussing ACP with their PCP. The primary outcome was
      provider-reported ACP discussion within three months. RESULTS: In the provider
      delivered patient incentive study, 38 PCPs were randomized to the intervention (n
      = 18) or control (n = 20) and given 10 patient packets each to distribute. Using
      an intention-to-treat analysis, there were 27 of 180 ACP discussions (15%) in the
      intervention group and 5 of 200 (2.5%) in the control group (P = .0391). In the
      mail-delivered patient incentive study, there were 5 of 187 ACP discussions
      (2.7%) in the intervention group and 5 of 189 (2.6%) in the control group (P =
      .99). CONCLUSION: ACP rates were low despite an existing provider financial
      incentive. Adding a provider-delivered patient financial incentive, but not a
      mail-delivered patient incentive, modestly increased ACP discussions. PCP
      encouragement combined with a patient incentive may be more powerful than either
      encouragement or incentive alone.

PMID- 28450219
TI  - Terminally Ill Taiwanese Cancer Patients' and Family Caregivers' Agreement on
      Patterns of Life-Sustaining Treatment Preferences Is Poor to Fair and Declines
      Over a Decade: Results From Two Independent Cross-Sectional Studies.
AB  - CONTEXT/OBJECTIVE: Temporal changes have not been examined in patient-caregiver
      agreement on life-sustaining treatment (LST) preferences at end of life (EOL). We
      explored the extent of and changes in patient-caregiver agreement on LST
      preference patterns for two independent cohorts of Taiwanese cancer patient
      family caregiver dyads recruited a decade apart. METHODS: We surveyed preferences
      for cardiopulmonary resuscitation, intensive care unit care, cardiac massage,
      intubation with mechanical ventilation, intravenous nutritional support, tube
      feeding, and dialysis among 1049 and 1901 dyads in 2003-2004 and 2011-2012,
      respectively. LST-preference patterns were examined by multi-group latent class
      analysis. Extent of patient-caregiver agreement on LST-preference patterns was
      determined by percentage agreement and kappa coefficients. RESULTS: For both
      patients and family caregivers, we identified seven distinct LST-preference
      classes. Patient-caregiver agreement on LST-preference patterns was poor to fair
      across both study cohorts, indicated by 24.4%-43.5% agreement and kappa values of
      0.06 (95% CI: 0.04, 0.09) to 0.27 (0.23, 0.30), and declined significantly over
      time. Agreement on LST-preference patterns was most likely when both patients and
      caregivers uniformly rejected LSTs. When patients disagreed with caregivers on
      LST-preference patterns, discrepancies were most likely when patients totally
      rejected LSTs but caregivers uniformly preferred LSTs or preferred nutritional
      support but rejected other treatments. CONCLUSION: Patients and family caregivers
      had poor-to-fair agreement on LST-preference patterns, and agreement declined
      significantly over a decade. Encouraging an open dialogue between patients and
      their family caregivers about desired EOL care would facilitate patient-caregiver
      agreement on LST-preference patterns, thus honoring terminally ill cancer
      patients' wishes when they cannot make EOL-care decisions.

PMID- 28450220
TI  - Feasibility and Pilot Studies in Palliative Care Research: A Systematic Review.
AB  - CONTEXT: Feasibility and pilot study designs are common in palliative care
      research. Finding standard guidelines on the structure and reporting of these
      study types is difficult. OBJECTIVES: In feasibility and pilot studies in
      palliative care research, to determine 1) how commonly a priori feasibility are
      criteria reported and whether results are subsequently reported against these
      criteria? and 2) how commonly are participants' views on acceptability of burden
      of the study protocol assessed? METHODS: Four databases (OVID Medline, EMBASE,
      CINAHL, and PubMed via caresearch.com.au.) were searched. Search terms included
      palliative care, terminal care, advance care planning, hospice, pilot,
      feasibility, with a publication date between January 1, 2012 and December 31,
      2013. Articles were selected and appraised by two independent reviewers. RESULTS:
      Fifty-six feasibility and/or pilot studies were included in this review. Only
      three studies had clear a priori criteria to measure success. Sixteen studies
      reported participant acceptability or burden with measures. Forty-eight studies
      concluded feasibility. CONCLUSION: The terms "feasibility" and "pilot" are used
      synonymously in palliative care research when describing studies that test for
      feasibility. Few studies in palliative care research outline clear criteria for
      success. The assessment of participant acceptability and burden is uncommon. A
      gold standard for feasibility study design in palliative care research that
      includes both clear criteria for success and testing of the study protocol for
      participant acceptability and burden is needed. Such a standard would assist with
      consistency in the design, conduct and reporting of feasibility and pilot
      studies.

PMID- 28450222
TI  - Probiotic treatment protects against the pro-depressant-like effect of high-fat
      diet in Flinders Sensitive Line rats.
AB  - Major depressive disorder (MDD) is highly associated with dysmetabolic
      conditions, such as obesity and diabetes mellitus type 2, and the gut microbiota
      may interact with both disease entities. We have previously shown that a high-fat
      diet (HFD) exacerbated depressive-like behaviour uniquely in Flinders Sensitive
      Line (FSL) rats that inherently present with an increased level of depressive
      like behaviour compared with Flinders Resistant Line (FRL) rats. We therefore
      investigated whether multispecies probiotics possessed anti-depressant-like
      effect in FSL rats or protected against the pro-depressant-like effect of HFD. We
      also examined blood and cerebral T cell subsets as well as plasma cytokines.
      Lastly, we investigated the effect of HFD in outbred Sprague-Dawley (SD) rats to
      substantiate the association between depressive-like behaviour and any
      immunological measures affected by HFD. HFD exacerbated the depressive-like
      behaviour in FSL rats in the forced swim test, whereas SD rats remained
      unaffected. Probiotic treatment completely precluded the pro-depressant-like
      effect of HFD, but it did not affect FSL rats on control diet. Cerebral T
      lymphocyte CD4/8 ratios closely mirrored the behavioural changes, whereas the
      proportions of Treg and Th17 subsets were unaltered. No association between blood
      and brain CD4/8 ratios were evident; nor did plasma cytokine levels change as a
      consequence of HFD of probiotic treatment. Our findings suggest that MDD may hold
      a dysmetabolic component that responds to probiotic treatment. This finding has
      wide implications owing to the high metabolic comorbidity in MDD. Furthermore,
      the close association between depressive-like behaviour and cerebral T cell
      populations demonstrate lymphocyte-brain interactions as a promising future
      research area in the field of psychoneuroimmunology.

PMID- 28450221
TI  - Mothers' childhood hardship forecasts adverse pregnancy outcomes: Role of
      inflammatory, lifestyle, and psychosocial pathways.
AB  - Research suggests the health consequences of economic hardship can be transmitted
      across generations. Some of these disparities are thought to be passed to
      offspring during gestation. But this hypothesis has not been tested in
      contemporary American samples, and the mechanisms of transmission have not been
      characterized. Accordingly, this study had two goals: first, to determine if
      women exposed to economic hardship during childhood showed higher rates of
      adverse birth outcomes; and second, to evaluate the contribution of inflammation,
      psychosocial, lifestyle, and obstetric characteristics to this phenomenon. This
      prospective study enrolled 744 women with singleton pregnancies (59.1% White;
      16.3% Black; 18.7% Latina; 5.9% Other). Childhood economic hardship was measured
      by self-report. Birth outcomes included length of gestation and incidence of
      preterm birth; birth weight percentile and small for gestational age; length of
      hospital stay and admission to Special Care Nursery. Analyses revealed that
      mothers' childhood economic hardship was independently associated with multiple
      adverse birth outcomes, even following adjustment for demographics, maternal
      education, and obstetrical confounders. Women raised in economically
      disadvantaged conditions had shorter gestation length and higher preterm delivery
      rates. Their babies had lower birth weights, were more likely to be small for
      gestational age, stayed in the hospital longer, and had more Special Care Nursery
      admissions. Mediation analyses suggested these associations arose through
      multiple pathways, and highlighted roles for inflammation, education, adiposity,
      and obstetric complications. Collectively, these findings suggest that childhood
      economic hardship predisposes women to adverse birth outcomes, and highlights
      likely behavioral and biological mechanisms.

PMID- 28450223
TI  - GPER activation is effective in protecting against inflammation-induced nigral
      dopaminergic loss and motor function impairment.
AB  - Increasing evidence suggest that excessive inflammatory responses from
      overactivated microglia play a critical role in Parkinson's disease (PD),
      contributing to, or exacerbating, nigral dopaminergic (DA) degeneration. Recent
      results from our group and others demonstrated that selective activation of G
      protein-coupled estrogen receptor (GPER) with the agonist G1 can protect DA
      neurons from 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) neurotoxins. However, it is not known whether
      modulation of microglial responses is one of the mechanisms by which G1 exerts
      its DA neuroprotective effects. We analyzed, in the N9 microglial cell line, the
      effect of G1 on microglial activation induced by lipopolysaccharide (LPS)
      exposure. The results revealed that G1 significantly decrease phagocytic
      activity, expression of inducible nitric oxide synthase (iNOS) and release of
      nitric oxide (NO) induced by LPS. To determine the relevance of this anti
      inflammatory effect to the protection of nigral DA cells, the effect of G1 was
      analyzed in male mice injected unilaterally in the substantia nigra (SN) with
      LPS. Although G1 treatment did not decrease LPS-induced increase of ionized
      calcium binding adaptor molecule 1 (iba-1) positive cells it significantly
      reduced interleukin-1beta (IL-1beta), cluster of differentiation 68 (CD68) and
      iNOS mRNA levels, and totally inhibited nigral DA cell loss and, as a
      consequence, protected the motor function. In summary, our findings demonstrated
      that the G1 agonist is able to modulate microglial responses and to protect DA
      neurons and motor functions against a lesion induced by an inflammatory insult.
      Since G1 lacks the feminizing effects associated with agonists of the classical
      estrogen receptors (ERs), the use of G1 to selectively activate the GPER may be a
      promising strategy for the development of new therapeutics for the treatment of
      PD and other neuroinflammatory diseases.

PMID- 28450224
TI  - Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of
      endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in
      rats.
AB  - Pulmonary hypertension is still not curable and the available current therapies
      can only alleviate symptoms without hindering the progression of disease. The
      present study was directed to investigate the possible modulatory effect of
      pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced
      pulmonary hypertension in rats. Pulmonary hypertension was induced by a single
      subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells
      were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being
      i.v. injected into rats 2weeks after monocrotaline administration. Four weeks
      after monocrotaline administration, blood pressure, electrocardiography and right
      ventricular systolic pressure were recorded. Rats were sacrificed and serum was
      separated for determination of endothelin-1 and asymmetric dimethylarginine
      levels. Right ventricles and lungs were isolated for estimation of tumor necrosis
      factor-alpha and transforming growth factor-beta contents as well as caspase-3
      activity. Moreover, protein expression of matrix metalloproteinase-9 and
      endothelial nitric oxide synthase in addition to myocardial connexin-43 was
      assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte
      cross-sectional area and right ventricular hypertrophy was performed and
      cryosections were done for estimation of cell homing. Preconditioning with
      pinocembrin provided a significant improvement in endothelial progenitor cells'
      effect towards reducing monocrotaline-induced elevation of inflammatory,
      fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a
      significant amelioration of endothelial markers and cell homing and prevented
      monocrotaline-induced changes in right ventricular function and histological
      analysis compared with native cells alone. In conclusion, pinocembrin
      significantly improves the therapeutic efficacy of endothelial progenitor cells
      in monocrotaline-induced pulmonary hypertension in rats.

PMID- 28450225
TI  - Ablation of IL-33 gene exacerbate myocardial remodeling in mice with heart
      failure induced by mechanical stress.
AB  - BACKGROUND AND PURPOSE: ST2 is one of the interleukin (IL)-1 receptor family
      members comprising of membrane-bound (ST2L) and soluble (sST2) isoforms. Clinical
      trials have revealed that serum sST2 levels predict outcome in patient with
      myocardial infarction or chronic heart failure (HF). Meanwhile, we and others
      have reported that ablation of ST2 caused exaggerated cardiac remodeling in both
      ischemic and non-ischemic HF. Here, we tested whether IL-33, the ligand for ST2,
      protects myocardium against HF induced by mechanical overload using ligand
      specific knockout (IL-33-/-) mice. METHODS AND RESULTS: Transverse aortic
      constriction (TAC)/sham surgery were carried out in both IL-33 and WT
      littermates. Echocardiographic measurements were performed at frequent interval
      during the study period. Heart was harvested for RNA and histological
      measurements. Following mechanical overload by TAC, myocardial mRNA expressions
      of Th1 cytokines, such as TNF-alpha were enhanced in IL-33-/- mice than in WT
      mice. After 8-weeks, IL-33-/- mice exhibited exacerbated left ventricular
      hypertrophy, increased chamber dilation, reduced fractional shortening,
      aggravated fibrosis, inflammation, and impaired survival compared with WT
      littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP)
      molecular markers were also significantly enhanced in IL-33-/- mice than those in
      WT mice. CONCLUSIONS: We report for the first time that ablation of IL-33
      directly and significantly leads to exacerbate cardiac remodeling with impaired
      cardiac function and survival upon mechanical stress. These data highlight the
      cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a
      potential therapeutic role for IL-33 in non-ischemic HF.

PMID- 28450226
TI  - Human carbonyl reductase 1 participating in intestinal first-pass drug metabolism
      is inhibited by fatty acids and acyl-CoAs.
AB  - Human carbonyl reductase 1 (CBR1), a member of the short-chain
      dehydrogenase/reductase (SDR) superfamily, reduces a variety of carbonyl
      compounds including endogenous isatin, prostaglandin E2 and 4-oxo-2-nonenal. It
      is also a major non-cytochrome P450 enzyme in the phase I metabolism of carbonyl
      containing drugs, and is highly expressed in the intestine. In this study, we
      found that long-chain fatty acids and their CoA ester derivatives inhibit CBR1.
      Among saturated fatty acids, myristic, palmitic and stearic acids were
      inhibitory, and stearic acid was the most potent (IC50 9uM). Unsaturated fatty
      acids (oleic, elaidic, gamma-linolenic and docosahexaenoic acids) and acyl-CoAs
      (palmitoyl-, stearoyl- and oleoyl-CoAs) were more potent inhibitors (IC50 1.0
      2.5uM), and showed high inhibitory selectivity to CBR1 over its isozyme CBR3 and
      other SDR superfamily enzymes (DCXR and DHRS4) with CBR activity. The inhibition
      by these fatty acids and acyl-CoAs was competitive with respect to the substrate,
      showing the Ki values of 0.49-1.2uM. Site-directed mutagenesis of the substrate
      binding residues of CBR1 suggested that the interactions between the fatty acyl
      chain and the enzyme's Met141 and Trp229 are important for the inhibitory
      selectivity. We also examined CBR1 inhibition by oleic acid in cellular levels:
      The fatty acid effectively inhibited CBR1-mediated 4-oxo-2-nonenal metabolism in
      colon cancer DLD1 cells and increased sensitivity to doxorubicin in the drug
      resistant gastric cancer MKN45 cells that highly express CBR1. The results
      suggest a possible new food-drug interaction through inhibition of CBR1-mediated
      intestinal first-pass drug metabolism by dietary fatty acids.

PMID- 28450227
TI  - Spatial phylogenetics of the vascular flora of Chile.
AB  - Current geographic patterns of biodiversity are a consequence of the evolutionary
      history of the lineages that comprise them. This study was aimed at exploring how
      evolutionary features of the vascular flora of Chile are distributed across the
      landscape. Using a phylogeny at the genus level for 87% of the Chilean vascular
      flora, and a geographic database of sample localities, we calculated phylogenetic
      diversity (PD), phylogenetic endemism (PE), relative PD (RPD), and relative PE
      (RPE). Categorical Analyses of Neo- and Paleo-Endemism (CANAPE) were also
      performed, using a spatial randomization to assess statistical significance. A
      cluster analysis using range-weighted phylogenetic turnover was used to compare
      among grid cells, and with known Chilean bioclimates. PD patterns were concordant
      with known centers of high taxon richness and the Chilean biodiversity hotspot.
      In addition, several other interesting areas of concentration of evolutionary
      history were revealed as potential conservation targets. The south of the country
      shows areas of significantly high RPD and a concentration of paleo-endemism, and
      the north shows areas of significantly low PD and RPD, and a concentration of neo
      endemism. Range-weighted phylogenetic turnover shows high congruence with the
      main macrobioclimates of Chile. Even though the study was done at the genus
      level, the outcome provides an accurate outline of phylogenetic patterns that can
      be filled in as more fine-scaled information becomes available.

PMID- 28450228
TI  - Mitogenomic phylogeny of cone snails endemic to Senegal.
AB  - Cone snails attain in Senegal one of their highest peaks of species diversity
      throughout the continental coast of Western Africa. A total of 15 endemic species
      have been described, all placed in the genus Lautoconus. While there is ample
      data regarding the morphology of the shell and the radular tooth of these
      species, virtually nothing is known regarding the genetic diversity and
      phylogenetic relationships of one of the most endangered groups of cones. In this
      work, we determined the complete or near-complete (only lacking the control
      region) mitochondrial (mt) genomes of 17 specimens representing 11 endemic
      species (Lautoconus belairensis, Lautoconus bruguieresi, Lautoconus cacao,
      Lautoconus cloveri, Lautoconus cf. echinophilus, Lautoconus guinaicus, Lautoconus
      hybridus, Lautoconus senegalensis, Lautoconus mercator, Lautoconus taslei, and
      Lautoconus unifasciatus). We also sequenced the complete mt genome of Lautoconus
      guanche from the Canary Islands, which has been related to the cones endemic to
      Senegal. All mt genomes share the same gene arrangement, which conforms to the
      consensus reported for Conidae, Neogastropoda and Caenogastropoda. Phylogenetic
      analyses using probabilistic methods recovered three major lineages, whose
      divergence coincided in time with sea level and ocean current changes as well as
      temperature fluctuations during the Messinian salinity crisis and the Plio
      Pleistocene transition. Furthermore, the three lineages corresponded to distinct
      types of radular tooth (robust, small, and elongated), suggesting that dietary
      specialization could be an additional evolutionary driver in the diversification
      of the cones endemic to Senegal. The reconstructed phylogeny showed several cases
      of phenotypic convergence (cryptic species) and questions the validity of some
      species (ecotypes or phenotypic plasticity), both results having important
      taxonomic and conservation consequences.

PMID- 28450229
TI  - Endoscopic Endonasal Surgery for Tumors of the Cavernous Sinus: A Series of 234
      Patients.
AB  - BACKGROUND: Cavernous sinus (CS) tumors often are considered inoperable. We
      present our experience with endoscopic endonasal surgery (EES) and compare the
      outcomes for different tumor. METHODS: EES (medial or lateral approach) was used
      in 234 patients with CS tumors. The cohort included 175 (75%) pituitary adenomas
      and 59 (25%) nonadenomatous lesions. RESULTS: Presenting symptoms were
      significantly different between the 2 groups, with cranial neuropathies occurring
      mainly in nonadenomas (P < 0.0001). The overall gross total tumor resection rate
      from the CS was 37.3% (37.1% in adenomas, 38.1% in non-adenomas). In total,
      preexisting cranial nerve (CN) dysfunction improved in 56.4% of the patients.
      After treatment completion (including radiation of residual tumor), 83.3% of
      acromegalic patients, 50% of prolactinomas and 33.3% of Cushing's disease, were
      in remission. Visual loss improved in 86.8% of adenomas and in 70.8% of
      nonadenomas. Intracavernous CN palsies improved in 77.3% of adenomas and 42.4% of
      nonadenomas. New permanent CN palsies occurred in 7 nonadenomas, which is
      significantly greater than in adenomas (P = 0.007). The leak rate of
      cerebrospinal fluid was 6.3% for adenomas and 11.9% for nonadenomas. Four
      patients suffered an internal carotid artery injury with no neurologic sequelae
      in 3 cases and 1 death (0.4%). CONCLUSIONS: EES provides an easily accessible
      midline corridor to the CS with equivalent or superior results to transcranial
      approaches in the management of select tumors. Symptomatology due to CS invasion
      is more likely to improve in pituitary adenomas and the rate of surgical
      complications is greater in nonadenomas. Using a team approach, the overall
      mortality due to vascular injury is low.

PMID- 28450230
TI  - Metastatic Alveolar Soft Part Sarcoma of the Spinal Cord: A Case Report and
      Review of Literature.
AB  - BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare, malignant soft-tissue
      neoplasm typically seen in young adults that possesses an unusual tendency to
      metastasize. Metastases to the intramedullary compartment of the spinal cord,
      however, are exceptionally rare and have not been described in the literature.
      CASE DESCRIPTION: We report the case of a 23-year-old woman with disseminated
      ASPS to the lung and brain who presented with progressive lower-extremity
      weakness and loss of sensation after radiation and chemotherapy. Magnetic
      resonance imaging revealed a 1.3-cm avidly enhancing lesion within the central
      thoracic spinal cord at T3. A T2-T4 laminectomy was undertaken and resulted in a
      gross total resection. Histopathologically, the mass was composed of organoid
      nests containing epithelioid cells with eosinophilic, granular cytoplasm
      separated by sinusoidal spaces. Immunohistochemistry demonstrated convincing
      positive TFE3 staining. Postoperative imaging confirmed the complete resection of
      the mass, and her examination was notable for intact sensation and impaired motor
      function that gradually improved. CONCLUSIONS: A review of the literature found
      that the reported case represents the first instance of primary or metastatic
      ASPS in the spinal cord. Metastatic ASPS should thus be included in the
      differential diagnosis in patients with known disease and neurologic impairment
      or back pain. Imaging of the spine should then be considered.

PMID- 28450231
TI  - Bow Hunter's Syndrome: Surgical Management (Video) and Review of the Literature.
AB  - BACKGROUND: Bow Hunter's syndrome (BHS) is a rare condition characterized by
      vertebrobasilar insufficiency associated with rotational vertebral artery
      occlusion during head movement. Many existing reports describe surgical
      management, although no single technique has proven superior. OBJECTIVE: To
      review all reported cases of BHS with focus on outcomes of individual techniques
      as well as to present a video report of a posterior decompression without fusion
      performed at the authors' institution. METHODS: We searched PubMed for all
      relevant articles of BHS available in the English language. Pertinent studies
      were further characterized into surgical technique performed and associated
      outcomes. RESULTS: We included 27 studies in our review, excluding the case
      presented, for a total of 65 cases of BHS. These cases discuss anterior versus
      posterior decompressions, the need for fusion, coil embolization techniques, the
      efficacy of intraoperative dynamic angiography, and success rate with symptom
      resolution being the primary endpoint. A total of 53 cases underwent
      decompression without fusion, with an overall success rate of 90.6% (n = 48/53).
      Similarly, eleven cases underwent decompression with fusion, with a success rate
      of 91% (n = 10/11). Two additional cases opted for coil embolization, one of
      which reported resolution of symptoms. Furthermore, we present a video case of a
      posterior decompression without fusion with resolution of symptoms. CONCLUSIONS:
      BHS remains a rare clinical condition with no clear superior method of treatment.
      Rates of symptom resolution are similar among cases undergoing decompression with
      or without fusion. Coil embolization has been reported with limited success in 2
      cases.

PMID- 28450232
TI  - Ossification of the Yellow Ligament Combined with Ossification of the Posterior
      Longitudinal Ligament at the Cervicothoracic Junction.
AB  - BACKGROUND: Both ossification of the yellow ligament (OYL) and the ossification
      of the posterior longitudinal ligament are relatively rare clinical entities. We
      report a extremely rare case of the spinal canal stenosis because of OYL, OPLL
      and listhesis at the cervicothoracic junction. CASE DESCRIPTION: A 69-year-old
      man had progressive pain over his bilateral axillar portion and right lower
      extremity for 1 year. Radiology showed cervical canal stenosis with ossification
      of OYL, OPLL, and listhesis at the cervicothoracic junction. Posterior
      decompression therapy was performed, and he recovered entirely from his symptoms.
      CONCLUSIONS: Triple factors of OYL, OPLL and listhesis contributed the cervical
      canal stenosis limited at cervicothoracic junction. Early diagnosis and surgical
      therapy is recommended for the good prognosis of this pathologic condition, as
      well as careful long-term follow-up for the early detection of its recurrence.

PMID- 28450234
TI  - Comparison of Two Three-Dimensional Printed Models of Complex Intracranial
      Aneurysms for Surgical Simulation.
AB  - OBJECTIVE: To compare two 3-dimensional (3D) printed models of intracranial
      aneurysms for simulation and training for complex aneurysm surgery. METHODS: The
      study included 6 complex or large aneurysm cases. We printed two 3D models of
      complex aneurysms based on computed tomography angiography data using a 3D
      printer: a whole model, which was all-in-one printed hollow aneurysm method with
      colorful and multiple materials and included the hollow aneurysm, adjacent
      arteries, skull base, and nerves, and a regional model that included the hollow
      aneurysm and adjacent arteries. The 3D models were used for surgical planning and
      for practice in craniotomy and clipping. Neurosurgeons rated the models via
      questionnaires. RESULTS: Both 3D aneurysm models were accurate: the diameter,
      width, and neck of the aneurysms in the models were not significantly different
      from the computed tomography angiography data (P > 0.05). Furthermore, the models
      were useful for selecting clips before surgery. The whole 3D model improved
      understanding of the surgical view more than the regional model did (P < 0.05);
      however, the clip application felt more realistic in the regional model (P <
      0.05). The process time for making the whole model is shorter (P < 0.05) but more
      expensive (P < 0.05) compared with the regional model. CONCLUSIONS: The whole and
      regional 3D printed aneurysm models were accurate. The whole model was more
      useful for planning the trajectory of approach to the aneurysm when it was
      located in close proximity to bone and nerves, whereas the regional 3D aneurysm
      model was appropriate for aneurysms not involving bone and nerves. This will help
      neurosurgeon choose the proper 3D model for the complex aneurysm surgery
      according to the comparison.

PMID- 28450233
TI  - Revisiting Adjuvant Radiotherapy After Gross Total Resection of World Health
      Organization Grade II Meningioma.
AB  - BACKGROUND: Atypical meningioma is a World Health Organization grade II tumor
      with intermediate prognosis and risk of recurrence. Optimal management after
      gross total resection (GTR) is controversial, with observation versus adjuvant
      radiotherapy (RT) contentiously debated. METHODS: Pathologic review was performed
      of all atypical meningiomas diagnosed at our institution from 1988 to 2011.
      Retrospective chart review documented patient demographics, extent of surgical
      resection, history of radiation therapy, progression-free survival (PFS), and
      overall survival (OS). A supplemental systematic literature review was completed
      in which English-language articles published since 1979 comparing observation and
      RT after GTR of atypical meningioma were surveyed. RESULTS: Sixty-nine patients
      met inclusion criteria. Sixty-one underwent observation, and 8 received RT.
      Overall, 15 observation and 3 patients undergoing RT experienced tumor recurrence
      (5-year PFS 79% vs. 88%; P = 0.67); 19 observation and 2 patients undergoing RT
      died (5-year OS 89% vs. 83%; P = 0.68). Systematic review identified 9 preceding
      studies reporting extractable data comparing observation and RT outcomes after
      GTR. Recurrence was 18% and 19% after observation and RT (P = 0.9); total
      survival was 84% and 93% (P = 0.2). At 5 years, PFS was 81% after observation and
      88% after RT (P = 0.2), whereas survival was 87% after observation and 96% after
      RT (P = 0.4). CONCLUSIONS: Observation alone after GTR of atypical meningioma was
      not associated with increased risk of tumor recurrence or mortality. Although
      some preceding authors advocate for RT based on empiric experience, a systematic
      review also suggests that observation may provide equivalent PFS and OS to RT.
      Taken together, these findings indicate that observation after GTR may be a safe
      alternative to RT.

PMID- 28450235
TI  - Repeat Stereotactic Radiosurgery for Locally Recurrent Brain Metastases.
AB  - PURPOSE/OBJECTIVES: The outcomes of repeat stereotactic radiosurgery (SRS) after
      failure of previous SRS are not well established. We report our overall
      experience using SRS for the retreatment of locally recurrent brain metastases.
      METHODS: Patients with brain metastases diagnosed between 2003 and 2015 who
      underwent repeat SRS for local tumor progression following prior SRS were
      identified. Rates of local control, radiation necrosis, and overall survival were
      analyzed. Factors affecting local failure and radiation necrosis were assessed by
      chi-square test. RESULTS: Twenty-four lesions in 22 patients underwent repeat SRS
      in a single fraction. Median age was 59 years. The median SRS-1 dose was 18 Gy,
      and the median SRS-2 dose was 15.5 Gy. The median SRS-1 target volume was 2.25
      cm3, and the median SRS-2 target volume was 3.30 cm3. The median follow-up from
      SRS-2 was 8.8 months. The actuarial local controls for SRS-2 were 94.1% and 61.1%
      at 6 and 12 months, respectively. The incidences of actuarial radiation necrosis
      were 9.2% and 9.2% at 6 and 12 months, respectively. Volume of tumor >4 cm3
      correlated with increased risk of local failure (P = 0.006) with no local
      failures recorded with volumes <=4 cm3. SRS-2 dose, cumulative SRS dose, receipt
      of whole brain radiotherapy, and use of SRS-2 as boost after surgery did not
      correlate with local failure or radiation necrosis. Median overall survival after
      SRS-2 was 8.78 months. CONCLUSION: Repeat SRS is feasible for select patients,
      particularly for those with tumor volume <=4 cm3. Further evaluation is needed to
      establish the most appropriate treatment doses and volumes for this approach.

PMID- 28450236
TI  - Iatrogenic Peripheral Nerve Injuries-Surgical Treatment and Outcome: 10 Years'
      Experience.
AB  - BACKGROUND: Iatrogenic nerve injuries are nerve injuries caused by medical
      interventions or inflicted accidentally by a treating physician. METHODS: We
      describe and analyze iatrogenic nerve injuries in a total of 122 consecutive
      patients who received surgical treatment at our Institution during a period of 10
      years, from January 1, 2003, to December 31, 2013. The final outcome evaluation
      was performed 2 years after surgical treatment. RESULTS: The most common causes
      of iatrogenic nerve injuries among patients in the study were the operations of
      bone fractures (23.9%), lymph node biopsy (19.7%), and carpal tunnel release
      (18%). The most affected nerves were median nerve (21.3%), accessory nerve (18%),
      radial nerve (15.6%), and peroneal nerve (11.5%). In 74 (60.7%) patients, surgery
      was performed 6 months after the injury, and in 48 (39.3%) surgery was performed
      within 6 months after the injury. In 80 (65.6%) patients, we found lesion in
      discontinuity, and in 42 (34.4%) patients lesion in continuity. The distribution
      of surgical procedures performed was as follows: autotransplantation (51.6%),
      neurolysis (23.8%), nerve transfer (13.9%), direct suture (8.2%), and resection
      of neuroma (2.5%). In total, we achieved satisfactory recovery in 91 (74.6%),
      whereas the result was dissatisfactory in 31 (25.4%) patients. CONCLUSIONS:
      Patients with iatrogenic nerve injuries should be examined as soon as possible by
      experts with experience in traumatic nerve injuries, so that the correct
      diagnosis can be reached and the appropriate therapy planned. The timing of
      reconstructive surgery and the technique used are the crucial factors for
      functional recovery.

PMID- 28450238
TI  - Osmolality of Orally Administered Solutions Influences Luminal Water Volume and
      Drug Absorption in Intestine.
AB  - Intestinal water absorption is reportedly influenced by luminal osmolality. In
      this study, we examined whether differences in the osmolality of the vehicle used
      for oral administration of drugs influence luminal water volume and drug
      absorption in the gastrointestinal (GI) tract, by means of in situ rat intestinal
      closed loop studies using solutions of fluorescein isothiocyanate dextran 4000 (a
      non-absorbable compound), atenolol (a low-permeability drug), and antipyrine (a
      high-permeability drug) in various solvents. Determination of the remaining
      fraction of water revealed the following rank order for water absorption in rat
      jejunum: purified water > saline > phosphate buffer = isosmotic mannitol
      solution. The luminal concentration of fluorescein isothiocyanate-dextran 4000
      after administration in purified water was significantly increased to 2.5 times
      the initial dosing concentration. Thus, osmolality-dependent changes in GI water
      absorption can cause significant changes of drug concentration in the GI fluid,
      potentially resulting in altered drug absorption characteristics. Indeed, the
      fraction absorbed of atenolol in jejunum was significantly greater when the drug
      was administered in purified water than in isosmotic solution. In contrast, no
      significant change in fraction absorbed of antipyrine was observed. Our results
      indicate that osmolality-dependent changes in GI water volume may influence drug
      absorption, especially of low-permeability drugs.

PMID- 28450237
TI  - A CRISPR-Cas9 Generated MDCK Cell Line Expressing Human MDR1 Without Endogenous
      Canine MDR1 (cABCB1): An Improved Tool for Drug Efflux Studies.
AB  - Madin-Darby canine kidney (MDCK) II cells stably transfected with transport
      proteins are commonly used models for drug transport studies. However, endogenous
      expression of especially canine MDR1 (cMDR1) confounds the interpretation of such
      studies. Here we have established an MDCK cell line stably overexpressing the
      human MDR1 transporter (hMDR1; P-glycoprotein), and used CRISPR-Cas9 gene editing
      to knockout the endogenous cMDR1. Genomic screening revealed the generation of a
      clonal cell line homozygous for a 4-nucleotide deletion in the canine ABCB1 gene
      leading to a frameshift and a premature stop codon. Knockout of cMDR1 expression
      was verified by quantitative protein analysis and functional studies showing
      retained activity of the human MDR1 transporter. Application of this cell line
      allowed unbiased reclassification of drugs previously defined as both substrates
      and non-substrates in different studies using commonly used MDCK-MDR1 clones. Our
      new MDCK-hMDR1 cell line, together with a previously developed control cell line,
      both with identical deletions in the canine ABCB1 gene and lack of cMDR1
      expression represent excellent in vitro tools for use in drug discovery.

PMID- 28450239
TI  - An Evolutionary Search Algorithm for Covariate Models in Population
      Pharmacokinetic Analysis.
AB  - Building a covariate model is a crucial task in population pharmacokinetics. This
      study develops a novel method for automated covariate modeling based on gene
      expression programming (GEP), which not only enables covariate selection, but
      also the construction of nonpolynomial relationships between pharmacokinetic
      parameters and covariates. To apply GEP to the extended nonlinear least squares
      analysis, the parameter consolidation and initial parameter value estimation
      algorithms were further developed and implemented. The entire program was coded
      in Java. The performance of the developed covariate model was evaluated for the
      population pharmacokinetic data of tobramycin. In comparison with the established
      covariate model, goodness-of-fit of the measured data was greatly improved by
      using only 2 additional adjustable parameters. Ten test runs yielded the same
      solution. In conclusion, the systematic exploration method is a potentially
      powerful tool for prescreening covariate models in population pharmacokinetic
      analysis.

PMID- 28450240
TI  - Correlation of FCGRT genomic structure with serum immunoglobulin, albumin and
      farletuzumab pharmacokinetics in patients with first relapsed ovarian cancer.
AB  - Farletuzumab (FAR) is a humanized monoclonal antibody (mAb) that binds to folate
      receptor alpha. A Ph3 trial in ovarian cancer patients treated with
      carboplatin/taxane plus FAR or placebo did not meet the primary statistical
      endpoint. Subgroup analysis demonstrated that subjects with high FAR exposure
      levels (Cmin>57.6MUg/mL) showed statistically significant improvements in PFS and
      OS. The neonatal Fc receptor (fcgrt) plays a central role in albumin/IgG stasis
      and mAb pharmacokinetics (PK). Here we evaluated fcgrt sequence and association
      of its promoter variable number tandem repeats (VNTR) and coding single
      nucleotide variants (SNV) with albumin/IgG levels and FAR PK in the Ph3 patients.
      A statistical correlation existed between high FAR Cmin and AUC in patients with
      the highest quartile of albumin and lowest quartile of IgG1. Analysis of fcgrt
      identified 5 different VNTRs in the promoter region and 9 SNVs within the coding
      region, 4 which are novel.

PMID- 28450241
TI  - Regulatory effects of galanin system on development of several age-related
      chronic diseases.
AB  - Age is a major risk factor for developing chronic diseases, including type 2
      diabetes, depression and Alzheimer's disease. The rapidly increase in the
      morbidity of these age-related chronic diseases is becoming a global problem.
      Although our understanding of these age-related diseases has tremendously been
      improved in recent years, certain aspects of their etiology and relative
      regulatory factors still remain elusive to clinicians and researchers. Emerging
      evidences suggest that neuropeptide galanin is involved in the pathogenesis of
      type 2 diabetes, depression and Alzheimer's disease. This article summarized
      relevant results of our and others studies to highlight the relationship between
      the galanin system and these age-related chronic diseases. On the one hand, a
      high galanin expression was found in subjects with type 2 diabetes, depression
      and Alzheimer's disease. On the other hand, current data suggest that galanin and
      its agonists (M617, M1145 and M1153) manifest the characters of anti-insulin
      resistance, anti-Alzheimer's disease and ameliorate or reinforce depression-like
      behavior. Specially, activation of GAL2 can alleviate those disease features in
      human and rodent models. These are helpful for us to understand the roles of
      galanin system in the pathogenesis of these age-related chronic diseases and to
      provide useful hints for the development of novel approaches to treat these
      complex diseases.

PMID- 28450242
TI  - Modulating carbohydrate-based hydrogels as viscoelastic lubricant substitute for
      articular cartilages.
AB  - Viscosupplementation is a therapeutic approach for osteoarthritis treatment,
      where the synovial fluid, the natural lubricant of the joints, is replaced by
      viscoelastic solutions with rheological properties comparable or better than the
      starting material. This study presents the development of an innovative platform
      for viscosupplementation, based on the optimization of polysaccharide-based
      colloidal hydrogel, aiming to reduce on-site enzyme degradation and enhance the
      possibility of hyaluronic acid substitution with alternative biomaterials.
      Catanionic vesicles are proposed as physical crosslinker that can guarantee the
      formation of a 'soft', tunable network, offering a dual-therapeutic approach: on
      the mechanical relief perspective, as well as on the drug/gene delivery strategy.
      This research focuses on the fabrication and optimization of colloidal networks,
      driven by the synergistic interaction among catanionic vesicles and cationic
      modified cellulose polymers. This study tests the hypothesis that cellulose-like
      polymers can be arranged into functional matrix, mimicking the mechanical
      properties of healthy synovial fluids.

PMID- 28450244
TI  - Radiation synthesis and drug delivery properties of interpenetrating networks
      (IPNs) based on poly(vinyl alcohol)/ methylcellulose blend hydrogels.
AB  - Gamma radiation was used to prepare blend hydrogels from poly(vinyl alcohol)
      (PVA) and low ratios of methylcellulose (MC). The structure-property behavior was
      characterized by IR spectroscopy, gel fraction, differential scanning calorimetry
      (DSC) and swelling at room temperature and different pH values. The PVA/MC
      hydrogels were used as a carrier for doxycycline hyclate (DOX-h) drug. The
      results showed that the gel fraction of PVA/MC hydrogels decreased greatly with
      increasing the ratio of MC in the initial feeding solution. The PVA/MC hydrogels
      displayed pH-sensitive swelling character. The drug uptake-release study
      indicated that PVA/MC hydrogels possessed controlled release behavior and that
      the release process depends on pH. In this respect, the release of DOX-h drug was
      significant in alkaline medium.

PMID- 28450243
TI  - Synthesis of MnO2/cellulose fiber nanocomposites for rapid adsorption of
      insecticide compound and optimization by response surface methodology.
AB  - The MnO2/Cellulose fiber Nanocomposites have been prepared via the microwave
      assisted hydrothermal method. The characteristic structure of MnO2/Cellulose
      fiber Nanocomposites was analyzed using X-ray diffraction, photoluminescence and
      UV-vis spectra, Transmission electron Microscopy, N2 adsorption-desorption and
      Scanning electron microscopy instrumental techniques. BET surface area and
      crystallite size values of MnO2/cellulose fiber nanocomposites have been found as
      87.064m2/g and 70.0nm, respectively. Response Surface Methodology (RSM) has been
      used for adsorption of Insecticide compound such as Toxaphene by prepared
      adsorbent. MnO2/Cellulose fiber Nanocomposites shows maximum removal of 96.5% at
      initial Toxaphene concentration of 5.0mg/L, pH 3 and adsorbent dose of 5.0g/L.
      Kinetic and equilibrium data follow pseudo-second order and Langmuir isotherm
      model, respectively. Adsorption capacity of MnO2/Cellulose fiber Nanocomposites
      has been found to be 5.465mg/g.

PMID- 28450245
TI  - Heterologous expression and biochemical studies of a thermostable glucose
      tolerant beta-glucosidase from Methylococcus capsulatus (bath strain).
AB  - Glucose inhibition of beta-glucosidase (BG) is a bottleneck in biomass
      hydrolysis. In this study, a glucose resistant GH1 beta-glucosidase gene- Mbgl
      from Methylococcus capsulatus (bath strain) was cloned and overexpressed in
      E.coli. The Ni-NTA affinity purified Mbgl displayed an optimum temperature of 70
      degrees C and optimum pH was 6.0. The calculated KM of the enzyme was 48.6mM and
      0.12mM for cellobiose and 4-Nitrophenyl beta-d-glucopyranoside (PNPG)
      respectively. PNPG hydrolysis in presence of various glucose concentrations
      showed that the enzyme was stimulated by ~2.2 fold at 50mM glucose and was not
      inhibited up to 450-500mM glucose. Homology modeling and structural comparisons
      of Mbgl with a glucose tolerant beta-glucosidase of Humicola insolens (HiBG)
      revealed that the Mbgl has a much broader active site unlike to a deep and narrow
      active site pocket of HiBG. The difference in active site shape reflects on an
      alternative mechanism of glucose tolerance in Mbgl. Supplementing a commercial
      cellulase enzyme mixture CTec with Mbgl in the hydrolysis of the pretreated rice
      straw enhanced the glucose yield by 10-15%. In addition, Mbgl was also stable in
      organic solvents, detergents and oxidative conditions which would be advantageous
      for biotechnological applications.

PMID- 28450246
TI  - Hypericum perforatum incorporated chitosan films as potential bioactive wound
      dressing material.
AB  - Recent studies in wound dressing applications offer new therapies and promote
      wound healing process. The aim of this study was to develop Hypericum perforatum
      (St John's Wort) oil incorporated chitosan films for wound dressing applications.
      H. perforatum oil as a potential therapeutic agent was encapsulated in chitosan
      film to achieve a better wound dressing material. Oil incorporated chitosan films
      were successfully prepared by solvent casting method in different oil
      concentrations (0.25-1.5%v/v). Water vapor permeability (WVP), mechanical test,
      swelling behavior and surface hydrophobicity were performed in order to
      characterize the prepared films. Antimicrobial test was performed by disc
      diffusion method and the growth inhibition effects of the films including
      different amount of H. perforatum oil were investigated on Escherichia coli and
      Staphylococcus aureus. WVP increased with oil incorporation and the highest value
      was obtained for 0.25% oil concentration.The highest strain value was obtained in
      0.25% oil content films although tensile stress decreased with increasing oil
      content. H. perforatum oil incorporated films had antimicrobial effect on both
      microorganisms. Chitosan based films had no cytotoxic effects on NIH3T3fibroblast
      cells and provided a good surface for cell attachment and proliferation. The
      results showed that the H. perforatum incorporated chitosan films seems to be a
      potential and novel biomaterial for wound healing applications.

PMID- 28450247
TI  - Incorporation of lysozyme-rectorite composites into chitosan films for
      antibacterial properties enhancement.
AB  - The demand for designing antibacterial materials was quite substantial in packing
      and biomedical materials fields. Chitosan had a wide utilization to satisfy this
      demand. In this study, by incorporating lysozyme (LY) - rectorite (REC) into
      chitosan films, the ultimately obtained hybrid films can own the enhanced
      antibacterial properties and still remains good mechanical properties. Scanning
      electron microscopy (SEM) images revealed that LY and REC could be homogeneously
      distributed in the CS films. X-ray photoelectron spectroscopy (XPS) and Energy
      dispersive X-ray analysis (EDX) results verified that the LY-REC incorporation
      process was successful. Small angle X-ray diffraction (SAXRD) and Fourier
      transform infrared (FT-IR) spectra revealed that some intercalation reactions
      occurred between CS chains and REC. The hydrophobic properties of the CS films
      were increased by the addition of LY and REC, determined by water contact angle
      measurement. In comparison with CS films, the mechanical properties of the
      composite films after adding LY-REC were reduced by 27.58%, but still maintained
      high tensile strength. Besides, the antibacterial properties of the films could
      be enhanced by introducing LY-REC. This method exhibited great application value
      in the food packaging fields.

PMID- 28450248
TI  - Fungal lytic polysaccharide monooxygenases from family AA9: Recent developments
      and application in lignocelullose breakdown.
AB  - Fungal lytic polysaccharide monooxygenases (LPMOs) from family AA9 are oxidative
      enzymes that, in the past few years, have changed the paradigm of cellulose
      conversion. They are key factor in the lignocellulose breakdown and are widely
      distributed among fungi. This review focuses on LPMOs from family AA9 and gives
      an overview of recent discoveries relative to their structure, mode of action,
      and synergism with other enzymes. Finally, several aspects regarding their
      potential applications toward deconstruction of biomass and biorefinery processes
      are discussed.

PMID- 28450249
TI  - Effect of xanthan and locust bean gum synergistic interaction on characteristics
      of biodegradable edible film.
AB  - The present study was aimed to use different combinations of xanthan (XG) and
      locust bean gum (LBG) in the biodegradable edible film preparation by benefitting
      from their synergistic interactions for the first time. Concentrations of LBG, XG
      and glycerol of the optimized film sample were found to be 89.6%, 10.4% and 20%,
      respectively. At the optimum point the WVP, TS, E% and EM values of film were
      found 0.22gmmh-1 m2kPa, 86.97MPa, 33.34% and 177.25MPa, respectively. The
      optimized film was characterized for its physical, thermal and structural
      behavior. The scanning electron microscopy (SEM), X-ray diffraction (XRD),
      differential scanning calorimetry (DSC) and fourier transform infrared
      spectroscopy (FTIR) analyses exhibited miscibility and presence of interaction
      between polymers. In conclusion, XG and LBG interaction was used successfully to
      get biodegradable films and coatings with improved characteristics.

PMID- 28450250
TI  - Deciphering the interactions of fish gelatine and hyaluronic acid in aqueous
      solutions.
AB  - The interactions of fish gelatine (FG) with hyaluronic acid (HA) are studied in
      an aqueous environment at 25 degrees C by turbidimetric titration, confocal
      scanning laser microscopy, dynamic light scattering, zeta potentiometry,
      spectrophotometry with methylene blue, and construction of state diagrams. FG
      forms soluble complexes with HA above a boundary pH (pHphi1), where both
      biopolymers are net-negatively charged, but develop insoluble complexes as liquid
      state complex coacervates below pHphi1, where the two biopolymers are oppositely
      charged. The insoluble complexes are continuously aggregated with further acid
      titration, followed by immediate visible phase-separation when another boundary
      pH (pHp) is reached. The complex formation is mainly driven by electrostatic
      attractions rather than hydrogen bonding or hydrophobic interactions. The complex
      formation is promoted by increasing FG-to-HA weight ratio or total biopolymer
      concentration, or at a low ionic strength, but significantly suppressed in the
      presence of high ionic strength.

PMID- 28450251
TI  - The facile synthesis of a chitosan Cu(II) complex by solution plasma process and
      evaluation of their antioxidant activities.
AB  - Synthesis of chitosan-Cu(II) complex by solution plasma process (SPP) irradiation
      was investigated. The effects of the distance between the electrodes, initial
      Cu(II) concentration, and initial pH on the Cu(II) adsorption capacity were
      evaluated. The results showed that narrower distance between the electrodes,
      higher initial Cu(II) concentration and higher initial pH (at pH<6) were
      favourable for the adsorption capacity of Cu(II). Characterization of the
      chitosan-Cu(II) complex by ultraviolet-visible (UV-vis), fourier transform
      infrared (FT-IR) and electron spin resonance (ESR) spectroscopy revealed that the
      main structure of chitosan was not changed after irradiation. Thermogravimetry
      (TG) analysis indicated that Cu(II) ions were well incorporated into the
      chitosan. The antioxidant activity of the chitosan-Cu(II) complex was evaluated
      by DPPH, ABTS, and reducing power assays. The chitosan-Cu(II) complex exhibited
      greater antioxidant activity than the original chitosan. Thus, SPP could be used
      for preparation of chitosan-Cu(II) complexes.

PMID- 28450252
TI  - Three-Dimensional Hysterosalpingo Contrast Sonography with Gel Foam: Methodology
      and Feasibility to Obtain 3-Dimensional Volumes of Tubal Shape.
AB  - OBJECTIVES: To investigate the feasibility of hysterosalpingo foam sonography
      (HyFoSy) with automated 3-dimensional (3D) software in the evaluation of tubal
      patency and visualization of the tubal course by obtaining a 3D volume
      acquisition of tubes. DESIGN: Prospective observational study (Canadian Task
      Force classification III). SETTING: University hospital. PATIENTS: A total of 132
      infertile females evaluated between October 2013 and February 2015.
      INTERVENTIONS: All patients underwent HyFoSy with the new automated 3D coded
      contrast imaging (CCI) followed by 2-dimensional (2D) real-time HyFoSy. To
      evaluate the feasibility of 3D visualization of the tubal course, consecutive
      volume acquisitions were performed during gel foam contrast agent injection.
      Conventional 2D real-time hysterosalpingo contrast sonography (HyCoSy) by
      detection of gel foam moving through the tubes and around the ovaries was finally
      performed and considered to indicate the final results of tubal status.
      MEASUREMENTS AND MAIN RESULTS: All the patients underwent 3D CCI HyFoSy, followed
      by 2D real-time HyFoSy. After both procedures, we observed 108 patients (81.8%)
      with bilateral tubal patency, 22 patients (16.6%) with unilateral tubal patency,
      and 2 patients (1.5%) with bilateral tubal occlusion. The concordance rate for
      tubal status between the first and second 3D volume acquisitions and the final 2D
      real-time evaluation was 84.8% and 97.0%, respectively. CONCLUSIONS: Transvaginal
      ultrasound HyFoSy with 3D volume reconstruction of the uterus and tubes is an
      accurate and safe technique that allows complete visualization of tubal shape and
      patency with high patient compliance.

PMID- 28450253
TI  - Laparoscopic Management of Autoamputated Ovary in Newborns: A Report of 2 Cases.
AB  - Intrauterine autoamputation of the ovary is an extremely rare diagnosis in the
      pediatric population. The current literature is limited to contradictory
      recommendations, while a standard management protocol for autoamputated adnexa
      secondary to intrauterine ovarian torsion is yet to be established. We report 2
      cases of auto-amputation of the ovary, leading to a free-floating intra-abdominal
      cyst in the newborn. Laparoscopic management was successful in both cases.

PMID- 28450254
TI  - Potential value of systematic reviews of qualitative evidence in informing user
      centered health and social care: findings from a descriptive overview.
AB  - OBJECTIVES: Systematic reviews of quantitative evidence are well established in
      health and social care. Systematic reviews of qualitative evidence are
      increasingly available, but volume, topics covered, methods used, and reporting
      quality are largely unknown. We provide a descriptive overview of systematic
      reviews of qualitative evidence assessing health and social care interventions
      included on the Database of Abstracts of Reviews of Effects (DARE). STUDY DESIGN
      AND SETTING: We searched DARE for reviews published between January 1, 2009, and
      December 31, 2014. We extracted data on review content and methods, summarized
      narratively, and explored patterns over time. RESULTS: We identified 145
      systematic reviews conducted worldwide (64 in the UK). Interventions varied but
      largely covered treatment or service delivery in community and hospital settings.
      There were no discernible patterns over time. Critical appraisal of primary
      studies was conducted routinely. Most reviews were poorly reported. CONCLUSION:
      Potential exists to use systematic reviews of qualitative evidence when driving
      forward user-centered health and social care. We identify where more research is
      needed and propose ways to improve review methodology and reporting.

PMID- 28450255
TI  - Hemophagocytic lymphohistiocytosis with high serum levels of IL-18 and
      predominant lymphocyte activation in a neonate born to a mother with adult-onset
      Still's disease.

PMID- 28450256
TI  - Proteomic identification of seminal plasma proteins related to the freezability
      of carp semen.
AB  - : The variation in sperm freezability among individuals within a fish species is
      a major factor justifying the identification of useful predictive indicators of
      cryopreservation success. It is unknown at present whether the protein
      composition of fish seminal plasma affects sperm freezability. Therefore, the
      aims of this study were to compare the proteome of carp seminal plasma from semen
      rated as good (GF) and poor (PF) freezability by two-dimensional difference gel
      electrophoresis followed by MALDI-TOF/TOF mass spectrometry. The semen was
      classified as GF and PF based on sperm motility assessment after freeze/thawing.
      Five spots representing three proteins were more abundant in GF, while ten spots
      representing seven proteins were more abundant in PF seminal plasma. The majority
      of proteins present in higher abundance in PF seminal plasma were associated with
      the innate immune response. On the other hand, higher freezability was associated
      with proteins involved in the maintenance of sperm membrane integrity and
      antioxidative protection. These results indicate that carp semen freezability
      levels may be related to different seminal plasma protein profiles. Lower
      usefulness of spermatozoa in cryopreservation may be related to previous
      infection or stress leading to sublethal changes to sperm structure.
      SIGNIFICANCE: Sperm quality parameters such as motility, viability and sperm
      concentration have been used as predictive tools of sperm cryopreservation
      potential in fish species However, the usefulness of initial motility parameters
      as indicators of freezability varies among fish species and between individuals
      within a species. Recent studies in mammals revealed that male-to-male
      variability in cryoresistance can be attributed to differences in seminal plasma
      protein composition. To the best of our knowledge, no proteomic studies linking
      the protein composition of fish seminal plasma and freezing resilience have been
      performed in fish. Our results indicate for the first time that factors
      regulating how carp semen tolerate cryopreservation may be related to the
      different protein profiles of carp seminal plasma. The obtained results provide
      new insight into understanding the molecular mechanisms underlying cryoresistance
      of carp semen and provide a tool for the improvement of a long-term sperm
      preservation procedure.

PMID- 28450257
TI  - A multifunctional microfluidic platform for generation, trapping and release of
      droplets in a double laminar flow.
AB  - Droplet microfluidics, involving micrometer-sized emulsion of droplets is a
      growing subfield of microfluidics which attracts broad interest due to its
      application on biological assays. Droplet-based systems have been used as
      microreactors as well as to encapsulate many biological entities for biomedical
      and biotechnological applications. Here, a novel microfluidic device is presented
      for the generation, trapping and release of aqueous including hydrogel droplets
      in a double laminar oil flow. This platform enables the storage and release of
      picoliter-sized droplets in two different carrier oils by using hydrodynamic
      forces without the need of electrical forces or optical actuators. Furthermore,
      this design allows droplets to be selectively and simultaneously exposed to two
      different conditions and collected on demand. Successful encapsulation of
      hepatoma H35 cells was performed on-chip. Viability of cell-laden droplets was
      performed off-chip to assess the potential applications in 3D encapsulation cell
      culture and drug discovery assays.

PMID- 28450258
TI  - Effects of wastewater treatment processes on the sludge reduction system with 2,4
      dichlorophenol: Sequencing batch reactor and anaerobic-anoxic-oxic process.
AB  - The effects of two wastewater treatment processes (sequencing batch reactor, SBR;
      and anaerobic-anoxic-oxic, A2O) on sludge reduction with metabolic uncoupler 2,4
      dichlorophenol (DCP) were studied in laboratory. The experimental results showed
      that the reduction of cumulative excess sludge in SBR and A2O was 43.7% and
      44.2%, respectively, during the stable stage of the test. The two processes had
      similar average sludge yield and sludge yield reduction, i.e., 0.306 and 0.305mg
      of SS/mg chemical oxygen demand (COD), and 16.9% and 17.8%, respectively. The
      effect of DCP on the wastewater treatment efficiencies (namely, removal of COD,
      total nitrogen, NH4+-N, and total phosphorus) of the two processes were also
      similar. SBR was more likely to slightly retard the increase of activated sludge
      SVI with lesser increase in extracellular polymeric substances and
      protein/polysaccharide ratio. Although DCP did not dramatically affect the
      microbial communities of sludge, SBR was more favorable for increasing the
      activated sludge SOUR and maintaining the primary microorganisms of sludge than
      A2O.

PMID- 28450259
TI  - Improving cellular robustness and butanol titers of Clostridium acetobutylicum
      ATCC824 by introducing heat shock proteins from an extremophilic bacterium.
AB  - In recent years, increasing concerns over environment, energy and climate have
      renewed interest in biotechnological production of butanol. However, growth
      inhibition by fermentation products and inhibitory components from raw biomass
      has hindered the development of acetone-butanol-ethanol (ABE) fermentation.
      Improving the cellular robustness of Clostridium acetobutylicum is of great
      importance for efficient ABE production. In this study, we attempted to improve
      the robustness and butanol titers of C. acetobutylicum ATCC824 by overexpressing
      GroESL and DnaK from the extremely radioresistant bacterium Deinococcus
      wulumuqiensis R12 and from C. acetobutylicum ATCC824 itself. Three recombinant
      strains were obtained and designated 824(dnaK R12), 824(groESL R12) and
      824(groESL824). These three recombinants were found to have significantly
      improved tolerances to stresses including butanol, furfural, oxidation and acid.
      Meanwhile, the butanol titers increased to 13.0g/L, 11.2g/L and 10.7g/L, which
      were 49.4%, 28.7% and 23.0% higher than that from the wild-type strain (8.7g/L),
      respectively. For 824(dnaK R12), the production of acetic and butyric acids
      decreased by 97.1% (1.4g/L vs. 0.04g/L) and 100% (0.3g/L vs. 0g/L), respectively,
      compared with the wild-type strain. Overexpressing GroESL and DnaK from D.
      wulumuqiensis R12 also resulted in better growth and ABE production than the wild
      type strain on fermentation in the presence of 2.5g/L furfural. Strain 824(groESL
      R12) was superior to 824(groESL 824) in diverse types of stress-tolerance and
      butanol titer, indicating that GroESL from the extremophilic bacterium could
      perform its function more efficiently in the heterologous host than native
      GroESL. Our study provides evidence that extremophilic bacteria can be excellent
      resources for engineering C. acetobutylicum to improve its robustness and butanol
      titer.

PMID- 28450260
TI  - Characterization of the arabinoxylan-degrading machinery of the thermophilic
      bacterium Herbinix hemicellulosilytica-Six new xylanases, three
      arabinofuranosidases and one xylosidase.
AB  - Herbinix hemicellulosilytica is a newly isolated, gram-positive, anaerobic
      bacterium with extensive hemicellulose-degrading capabilities obtained from a
      thermophilic biogas reactor. In order to exploit its potential as a source for
      new industrial arabinoxylan-degrading enzymes, six new thermophilic xylanases,
      four from glycoside hydrolase family 10 (GH10) and two from GH11, three
      arabinofuranosidases (1x GH43, 2x GH51) and one beta-xylosidase (GH43) were
      selected. The recombinantly produced enzymes were purified and characterized. All
      enzymes were active on different xylan-based polysaccharides and most of them
      showed temperature-vs-activity profiles with maxima around 55-65 degrees C. HPAEC
      PAD analysis of the hydrolysates of wheat arabinoxylan and of various purified
      xylooligosaccharides (XOS) and arabinoxylooligosaccharides (AXOS) was used to
      investigate their substrate and product specificities: among the GH10 xylanases,
      XynB showed a different product pattern when hydrolysing AXOS compared to XynA,
      XynC, and XynD. None of the GH11 xylanases was able to degrade any of the tested
      AXOS. All three arabinofuranosidases, ArfA, ArfB and ArfC, were classified as
      type AXH-m,d enzymes. None of the arabinofuranosidases was able to degrade the
      double-arabinosylated xylooligosaccharides XA2+3XX. beta-Xylosidase XylA (GH43)
      was able to degrade unsubstituted XOS, but showed limited activity to degrade
      AXOS.

PMID- 28450261
TI  - Monitoring gene expression of rcpA from Aggregatibacter actinomycetemcomitans
      versus antimicrobial photodynamic therapy by relative quantitative real-time PCR.
AB  - BACKGROUND: Aggregatibacter actinomycetemcomitans is an important pathogen that
      is frequently found in various infections, particularly aggressive periodontitis.
      In this study, we described the outcome of the expression level of A.
      actinomycetemcomitans virulence factor following treatment by antimicrobial
      photodynamic therapy (aPDT) with indocyanine green (ICG) as a photosensitizing
      agent. MATERIALS AND METHODS: To determine the aPDT effect on the cell-surviving
      assay and expression ratio of the rcpA gene in A. actinomycetemcomitans by a
      colony-forming unit and relative quantitative (q) real-time PCR (qRT-PCR) assays,
      respectively, the proper dosing of sub-lethal aPDT was specified. RESULTS: The
      results of the current study showed that ICG-mediated aPDT, using 250-1000MUg/mL,
      showed a significant reduction in A. actinomycetemcomitans growth when compared
      to the control group (P<0.05). Also, a sub-lethal dose of aPDT against A.
      actinomycetemcomitans was 125MUg/mL ICG, with a 30s diode laser irradiation time
      at fluency of 15.6J/cm2 that could reduce the expression of rcpA gene
      approximately 6-fold. DISCUSSION: aPDT with ICG could reduce the cell survival
      and the virulence agent of A. actinomycetemcomitans. Thus, use of the appropriate
      aPDT dosage can be used for the successful treatment of periodontitis in vivo.

PMID- 28450262
TI  - Evaluation of photodynamic therapy in treatment of oral erosive lichen planus in
      comparison with topically applied corticosteroids.
AB  - BACKGROUND: The treatment of erosive oral lichen planus represents a therapeutic
      challenge. Despite numerous existing remedies, some of these treatments display
      disappointing results. Since it is a chronic disease with no current cure, the
      best treatment should target mainly the reduction of the duration and severity of
      symptomatic outbreaks with minimal side effects. To date, corticosteroids remain
      the first choice of treatment for oral lichen planus (OLP) patients. Although,
      topical corticosteroids have been found to be the safest and the most successful
      agents in the treatment of OLP, their prolonged use may cause mucosal problems
      and may lead to systemic complications. Recently, the use of photodynamic therapy
      has been well introduced in the treatment of oral diseases. Our clinical study
      was done to evaluate clinically the effect of photodynamic therapy mediated by
      methylene blue (MB-PDT) on signs and symptoms of erosive oral lichen planus
      (EOLP) lesions in comparison with the conventional topical corticosteroids (TC)
      treatment. The present work tried this recent modality of treatment to overcome
      the disadvantages of TC. MATERIAL AND METHODS: Twenty patients with clinical and
      histological diagnosis of EOLP were selected from Oral Medicine and
      periodontology department in Faculty of Dentistry, Alexandria University in a
      randomized parallel study design. They were divided into two groups; group A
      (control group) involved ten patients who were instructed to use the conventional
      TC (kenakort A-orabase). While, group B (study group) contained ten patients who
      received PDT using diode laser 660nm mediated by methylene blue (MB). RESULTS:
      Both groups presented statistically significant difference from baseline to
      follow up periods. But, the MB-PDT in treatment of EOLP showed more remarkable
      reduction in pain and lesion scores in comparison with corticosteroids treatment.
      CONCLUSION: The results of this study allow the conclusion that the MB-PDT is
      considered to be a better treatment for OELP in comparison with TC because it is
      much more effective in pain reduction and lesion regression.

PMID- 28450263
TI  - Wls expression in the rhombic lip orchestrates the embryonic development of the
      mouse cerebellum.
AB  - Wntless (Wls) is implicated in the Wnt signaling pathway by regulating the
      secretion of Wnt molecules. During brain development, Wls is expressed in the
      isthmic organizer (ISO) and rhombic lip (RL). Wls regulates Wnt1 secretion at the
      ISO which is required to induce midbrain-hindbrain structures. However, Wls
      function in the RL is not known. Here, we employed Nestin-cre to delete Wls
      specifically in the RL during mid-gestation. The loss-of-Wls leads to an abnormal
      RL during development and cerebellar vermis hypoplasia at birth. The Wls
      conditional knockout (cKO) has rudimentary foliation with an absence of Bergmann
      glia fibers in the external germinal layer (EGL). The Wls-cKO cerebellum also
      exhibits ectopia of several cell types and aberrations in granule cell
      organization. Finally, there is a loss of 85% of unipolar brush cells. From these
      findings, Wls-expressing cells in the rhombic lip are implicated in the
      orchestration of cerebellar development.

PMID- 28450264
TI  - Neural dynamics underlying varying attentional control facing invariant cognitive
      task upon invariant stimuli.
AB  - Even when performing invariant behavioral task repeatedly on invariant physical
      stimuli, our behavioral performance always changes as manifested in varying
      response times (RTs), which is associated with fluctuations in attentional
      control and thus the underlying self-organization states of the human brain. In a
      visuospatial task of the present fMRI study, physical stimuli differed across six
      levels of spatial scope, but were kept invariant within each level. The slower
      RTs with larger spatial area attended suggested higher demands on visuospatial
      attention. The slower RTs within each level, however, implicated worse
      attentional control since both the task and the physical stimuli were kept
      invariant within each level. The imaging results showed that slower RTs within
      each of the six levels were associated with higher but later activations in the
      frontoparietal network, and higher but later deactivations in the default-mode
      network (DMN). These findings thus for the first time suggested that the within
      level variance of attentional control corresponded to dynamic changes in the
      frontoparietal network and the DMN, in terms of not only the height but also the
      latency of neural activity. Moreover, although the two networks are anti
      correlated in terms of the height of neural activity, they are tightly coupled in
      terms of the temporal dynamics. Based on the current results, we proposed a
      tentative hypothesis on the optimal working mode of the frontoparietal
      attentional control system in the human brain: even a lower height of neural
      activity in frontoparietal network can significantly improve behavioral
      performance as long as it starts relatively early.

PMID- 28450265
TI  - Construct and face validity of a new model for the three-hit theory of depression
      using PACAP mutant mice on CD1 background.
AB  - Major depression is a common cause of chronic disability. Despite decades of
      efforts, no equivocally accepted animal model is available for studying
      depression. We tested the validity of a new model based on the three-hit concept
      of vulnerability and resilience. Genetic predisposition (hit 1, mutation of
      pituitary adenylate cyclase-activating polypeptide, PACAP gene), early-life
      adversity (hit 2, 180-min maternal deprivation, MD180) and chronic variable mild
      stress (hit 3, CVMS) were combined. Physical, endocrinological, behavioral and
      functional morphological tools were used to validate the model. Body- and adrenal
      weight changes as well as corticosterone titers proved that CVMS was effective.
      Forced swim test indicated increased depression in CVMS PACAP heterozygous (Hz)
      mice with MD180 history, accompanied by elevated anxiety level in marble burying
      test. Corticotropin-releasing factor neurons in the oval division of the bed
      nucleus of the stria terminalis showed increased FosB expression, which was
      refractive to CVMS exposure in wild-type and Hz mice. Urocortin1 neurons became
      over-active in CMVS-exposed PACAP knock out (KO) mice with MD180 history,
      suggesting the contribution of centrally projecting Edinger-Westphal nucleus to
      the reduced depression and anxiety level of stressed KO mice. Serotoninergic
      neurons of the dorsal raphe nucleus lost their adaptation ability to CVMS in
      MD180 mice. In conclusion, the construct and face validity criteria suggest that
      MD180 PACAP HZ mice on CD1 background upon CVMS may be used as a reliable model
      for the three-hit theory.

PMID- 28450266
TI  - Dynamic features of animate motion activate septal and preoptic areas in visually
      naive chicks (Gallus gallus).
AB  - The septum is an evolutionarily well-conserved part of the limbic system. It is
      known to be involved in many aspects of social behavior and is considered a key
      node of the social behavior network, together with the preoptic area. Involvement
      of these two brain regions has been recently observed in newly hatched chicks
      exposed to the natural motion of a living conspecific. However, it is unknown
      whether these areas respond also to simple motion cues that elicit animacy
      perception in humans and social predispositions in chicks. For example, naive
      chicks are attracted by visual objects that appear to spontaneously change their
      speed (an index of self-propulsion, typical of animate creatures). Here we show
      that the right septum and the preoptic area of newly hatched visually naive
      chicks exposed to speed changes have higher neuronal activity (revealed by c-Fos
      expression), compared with that of chicks exposed to constant motion. We thus
      found an involvement of these two areas in the perception of motion cues
      associated with animacy in newly hatched chicks without any previous visual
      experience. This demonstrates their early involvement in processing simple motion
      cues that allow the detection of animate creatures and elicit social
      predispositions in this animal model, as well as preferential attention in human
      infants and the perception of animacy in human adults.

PMID- 28450269
TI  - In vivo prion models and the disconnection between transmissibility and
      neurotoxicity.
AB  - The primary causative event in the development of prion diseases is the
      misfolding of the normal prion protein (PrPC) into an ensemble of altered
      conformers (herein collectively denoted as PrPSc) that accumulate in the brain.
      Prominent amongst currently unresolved key aspects underpinning prion disease
      pathogenesis is whether transmission and toxicity are sub-served by different
      molecular species of PrPSc, which may directly impact on the development of
      effective targeted treatments. The use of murine models of prion disease has been
      of fundamental importance for probing the relationship between hypothesised
      "neurotoxic" and "transmissible" PrPSc and the associated kinetic profiles of
      their production during disease evolution, but unfortunately consensus has not
      been achieved. Recent in vivo studies have led to formulation of the "two-phase"
      hypothesis, which postulates that there is first an exponential increase in
      transmitting PrPSc species followed by an abrupt transition to propagation of
      neurotoxic PrPSc species. Such observations however, appear inconsistent with
      previous in vivo murine studies employing detailed time-course behavioural
      testing, wherein evidence of neurotoxicity could be detected early in disease
      progression. This review analyses the contributions of in vivo murine models
      attempting to provide insights into the relationship between transmitting and
      neurotoxic PrPSc species and explores possible refinements to the "two-phase
      hypothesis", that better accommodate the available historical and recent
      evidence.

PMID- 28450268
TI  - Extensive uptake of alpha-synuclein oligomers in astrocytes results in sustained
      intracellular deposits and mitochondrial damage.
AB  - The presence of Lewy bodies, mainly consisting of aggregated alpha-synuclein, is
      a pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies
      (DLB). The alpha-synuclein inclusions are predominantly found in neurons, but
      also appear frequently in astrocytes. However, the pathological significance of
      alpha-synuclein inclusions in astrocytes and the capacity of glial cells to clear
      toxic alpha-synuclein species remain unknown. In the present study we
      investigated uptake, degradation and toxic effects of oligomeric alpha-synuclein
      in a co-culture system of primary neurons, astrocytes and oligodendrocytes. Alpha
      synuclein oligomers were found to co-localize with the glial cells and the
      astrocytes were found to internalize particularly large amounts of the protein.
      Following ingestion, the astrocytes started to degrade the oligomers via the
      lysosomal pathway but, due to incomplete digestion, large intracellular deposits
      remained. Moreover, the astrocytes displayed mitochondrial abnormalities. Taken
      together, our data indicate that astrocytes play an important role in the
      clearance of toxic alpha-synuclein species from the extracellular space. However,
      when their degrading capacity is overburdened, alpha-synuclein deposits can
      persist and result in detrimental cellular processes.

PMID- 28450267
TI  - Retinal changes in the Tg-SwDI mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD), a debilitating neurodegenerative illness, is
      characterized by neuronal cell loss, mental deficits, and abnormalities in
      several neurotransmitter and protein systems. AD is also associated with visual
      disturbances, but their causes remain unidentified. We hypothesize that the
      visual disturbances stem from retinal changes, particularly changes in the
      retinal cholinergic system, and that the etiology in the retina parallels the
      etiology in the rest of the brain. To test our hypothesis, quantitative
      polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were employed to
      assess changes in acetylcholine receptor (AChR) gene expression, number of
      retinal cells, and astrocytic gliosis in the Transgenic Swedish, Dutch and Iowa
      (Tg-SwDI) mouse model as compared to age-matched wild-type (WT). We observed that
      Tg-SwDI mice showed an initial upregulation of AChR gene expression early on
      (young adults and middle-aged adults), but a downregulation later on (old
      adults). Furthermore, transgenic animals displayed significant cell loss in the
      photoreceptor layer and inner retina of the young adult animals, as well as
      specific cholinergic cell loss, and increased astrocytic gliosis in the middle
      aged adult and old adult groups. Our results suggest that the changes observed in
      AD cerebrum are also present in the retina and may be, at least in part,
      responsible for the visual deficits associated with the disease.

PMID- 28450270
TI  - Pro-resolution therapeutics for cardiovascular diseases.
AB  - Studies over the last couple of decades suggest that failed resolution of a
      chronic inflammatory response is an important driving force in the progression of
      atherosclerosis. Resolution of inflammation is mediated in part by lipid-derived
      specialized pro-resolving mediators (SPMs) such as lipoxins, resolvins,
      protectins and maresins. The major functions of SPMs are to quell inflammation
      and repair tissue damage in a manner that does not compromise host defense. An
      imbalance between SPMs and pro-inflammatory mediators like leukotriene B4 (LTB4)
      are associated with several prevalent human diseases, including atherosclerosis.
      Because atherosclerosis is marked by persistent, unresolved inflammation and
      arterial tissue injury, SPMs have garnered immense interest as a potential
      treatment strategy. This mini review will highlight recent advances in the
      application of SPMs in atherosclerosis as well as the ability of SPMs to control
      several of the risk factors associated with cardiovascular diseases.

PMID- 28450271
TI  - Social Health Inequalities and eHealth: A Literature Review With Qualitative
      Synthesis of Theoretical and Empirical Studies.
AB  - BACKGROUND: eHealth is developing rapidly and brings with it a promise to reduce
      social health inequalities (SHIs). Yet, it appears that it also has the potential
      to increase them. OBJECTIVES: The general objective of this review was to set out
      how to ensure that eHealth contributes to reducing SHIs rather than exacerbating
      them. This review has three objectives: (1) identifying characteristics of people
      at risk of experiencing social inequality in health; (2) determining the
      possibilities of developing eHealth tools that avoid increasing SHI; and (3)
      modeling the process of using an eHealth tool by people vulnerable to SHI.
      METHODS: Following the EPPI approach (Evidence for Policy and Practice of
      Information of the Institute of Education at the University of London), two
      databases were searched for the terms SHIs and eHealth and their derivatives in
      titles and abstracts. Qualitative, quantitative, and mixed articles were included
      and evaluated. The software NVivo (QSR International) was employed to extract the
      data and allow for a metasynthesis of the data. RESULTS: Of the 73 articles
      retained, 10 were theoretical, 7 were from reviews, and 56 were based on
      empirical studies. Of the latter, 40 used a quantitative approach, 8 used a
      qualitative approach, 4 used mixed methods approach, and only 4 were based on
      participatory research-action approach. The digital divide in eHealth is a
      serious barrier and contributes greatly to SHI. Ethnicity and low income are the
      most commonly used characteristics to identify people at risk of SHI. The most
      promising actions for reducing SHI via eHealth are to aim for universal access to
      the tool of eHealth, become aware of users' literacy level, create eHealth tools
      that respect the cultural attributes of future users, and encourage the
      participation of people at risk of SHI. CONCLUSIONS: eHealth has the potential to
      widen the gulf between those at risk of SHI and the rest of the population. The
      widespread expansion of eHealth technologies calls for rigorous consideration of
      interventions, which are not likely to exacerbate SHI.

PMID- 28450272
TI  - Evaluation of a Web-Based Tailored Nursing Intervention (TAVIE en m@rche) Aimed
      at Increasing Walking After an Acute Coronary Syndrome: A Multicenter Randomized
      Controlled Trial Protocol.
AB  - BACKGROUND: Despite the health benefits of increasing physical activity in the
      secondary prevention of acute coronary syndrome (ACS), up to 60% of ACS patients
      are insufficiently active. Evidence supporting the effect of Web-based
      interventions on increasing physical activity outcomes in ACS patients is
      growing. However, randomized controlled trials (RCTs) using Web-based
      technologies that measured objective physical activity outcomes are sparse.
      OBJECTIVE: Our aim is to evaluate in insufficiently active ACS patients, the
      effect of a fully automated, Web-based tailored nursing intervention (TAVIE en
      m@rche) on increasing steps per day. METHODS: A parallel two-group multicenter
      RCT (target N=148) is being conducted in four major teaching hospitals in
      Montreal, Canada. An experimental group receiving the 4-week TAVIE en m@rche
      intervention plus a brief "booster" at 8 weeks, is compared with the control
      group receiving hyperlinks to publicly available websites. TAVIE en m@rche is
      based on the Strengths-Based Nursing Care orientation to nursing practice and the
      Self-Determination Theory of human motivation. The intervention is centered on
      videos of a nurse who delivers the content tailored to baseline levels of self
      reported autonomous motivation, perceived competence, and walking behavior.
      Participants are recruited in hospital and are eligible if they report access to
      a computer and report less than recommended physical activity levels 6 months
      before hospitalization. Most outcome data are collected online at baseline, and 5
      and 12 weeks postrandomization. The primary outcome is change in accelerometer
      measured steps per day between randomization and 12 weeks. The secondary outcomes
      include change in steps per day between randomization and 5 weeks, and change in
      self-reported energy expenditure for walking and moderate to vigorous physical
      activity between randomization, and 5 and 12 weeks. Theoretical outcomes are the
      mediating role of self-reported perceived autonomy support, autonomous and
      controlled motivations, perceived competence, and barrier self-efficacy on steps
      per day. Clinical outcomes are quality of life, smoking, medication adherence,
      secondary prevention program attendance, health care utilization, and angina
      frequency. The potential moderating role of sex will also be explored. Analysis
      of covariance models will be used with covariates such as sex, age, fatigue, and
      depression symptoms. Allocation sequence is concealed, and blinding will be
      implemented during data analysis. RESULTS: Recruitment started March 30, 2016.
      Data analysis is planned for November 2017. CONCLUSIONS: Finding alternative
      interventions aimed at increasing the adoption of health behavior changes such as
      physical activity in the secondary prevention of ACS is clearly needed. Our RCT
      is expected to help support the potential efficacy of a fully automated, Web
      based tailored nursing intervention on the objective outcome of steps per day in
      an ACS population. If this RCT is successful, and after its implementation as
      part of usual care, TAVIE en m@rche could help improve the health of ACS patients
      at large. TRIAL REGISTRATION: ClinicalTrials.gov NCT02617641;
      https://clinicaltrials.gov/ct2/show/NCT02617641 (Archived by WebCite at
      http://www.webcitation.org/6pNNGndRa).

PMID- 28450273
TI  - Importance-Performance Analysis of Personal Health Records in Taiwan: A Web-Based
      Survey.
AB  - BACKGROUND: Empowering personal health records (PHRs) provides basic human right,
      awareness, and intention for health promotion. As health care delivery changes
      toward patient-centered services, PHRs become an indispensable platform for
      consumers and providers. Recently, the government introduced "My health bank," a
      Web-based electronic medical records (EMRs) repository for consumers. However, it
      is not yet a PHR. To date, we do not have a platform that can let patients manage
      their own PHR. OBJECTIVE: This study creates a vision of a value-added platform
      for personal health data analysis and manages their health record based on the
      contents of the "My health bank." This study aimed to examine consumer
      expectation regarding PHR, using the importance-performance analysis. The purpose
      of this study was to explore consumer perception regarding this type of a
      platform: it would try to identify the key success factors and important aspects
      by using the importance-performance analysis, and give some suggestions for
      future development based on it. METHODS: This is a cross-sectional study
      conducted in Taiwan. Web-based invitation to participate in this study was
      distributed through Facebook. Respondents were asked to watch an introductory
      movie regarding PHR before filling in the questionnaire. The questionnaire was
      focused on 2 aspects, including (1) system functions, and (2) system design and
      security and privacy. The questionnaire would employ 12 and 7 questions
      respectively. The questionnaire was designed following 5-points Likert scale
      ranging from 1 ("disagree strongly") to 5 ("Agree strongly"). Afterwards, the
      questionnaire data was sorted using IBM SPSS Statistics 21 for descriptive
      statistics and the importance-performance analysis. RESULTS: This research
      received 350 valid questionnaires. Most respondents were female (219 of 350
      participants, 62.6%), 21-30 years old (238 of 350 participants, 68.0%), with a
      university degree (228 of 350 participants, 65.1%). They were still students (195
      out of 350 participants, 56.6%), with a monthly income of less than NT $30,000
      (230 of 350 participants, 65.7%), and living in the North Taiwan (236 of 350
      participants, 67.4%), with a good self-identified health status (171 of 350
      participants, 48.9%). After performing the importance-performance analysis, we
      found the following: (1) instead of complex functions, people just want to have a
      platform that can let them integrate and manage their medical visit, health
      examination, and life behavior records; (2) they do not care whether their PHR is
      shared with others; and (3) most of the participants think the system security
      design is not important, but they also do not feel satisfied with the current
      security design. CONCLUSIONS: Overall, the issues receiving the most user
      attention were the system functions, circulation, integrity, ease of use, and
      continuity of the PHRs, data security, and privacy protection.

PMID- 28450275
TI  - Evolution of biological agents: how established drugs can become less safe.

PMID- 28450274
TI  - Establishing Linkages Between Distributed Survey Responses and Consumer Wearable
      Device Datasets: A Pilot Protocol.
AB  - BACKGROUND: As technology increasingly becomes an integral part of everyday life,
      many individuals are choosing to use wearable technology such as activity
      trackers to monitor their daily physical activity and other health-related goals.
      Researchers would benefit from learning more about the health of these
      individuals remotely, without meeting face-to-face with participants and avoiding
      the high cost of providing consumer wearables to participants for the study
      duration. OBJECTIVE: The present study seeks to develop the methods to collect
      data remotely and establish a linkage between self-reported survey responses and
      consumer wearable device biometric data, ultimately producing a de-identified and
      linked dataset. Establishing an effective protocol will allow for future studies
      of large-scale deployment and participant management. METHODS: A total of 30
      participants who use a Fitbit will be recruited on Mechanical Turk Prime and
      asked to complete a short online self-administered questionnaire. They will also
      be asked to connect their personal Fitbit activity tracker to an online third
      party software system, called Fitabase, which will allow access to 1 month's
      retrospective data and 1 month's prospective data, both from the date of consent.
      RESULTS: The protocol will be used to create and refine methods to establish
      linkages between remotely sourced and de-identified survey responses on health
      status and consumer wearable device data. CONCLUSIONS: The refinement of the
      protocol will inform collection and linkage of similar datasets at scale,
      enabling the integration of consumer wearable device data collection in cross
      sectional and prospective cohort studies.

PMID- 28450276
TI  - Pregnancy and bile acid disorders.
AB  - During pregnancy, extensive adaptations in maternal metabolic and immunological
      physiology occur. Consequently, preexisting disease may be exacerbated or
      attenuated, and new disease susceptibility may be unmasked. Cholestatic diseases,
      characterized by a supraphysiological raise in bile acid levels, require careful
      monitoring during pregnancy. This review describes the latest advances in the
      knowledge of intrahepatic cholestasis of pregnancy (ICP), the most common bile
      acid disorder specific to pregnancy, with a focus on the disease etiology and
      potential mechanisms of ICP-associated adverse pregnancy outcomes, including
      fetal demise. The course of preexisting cholestatic conditions in pregnancy is
      considered, including primary sclerosing cholangitis, primary biliary
      cholangitis, biliary atresia, and Alagille syndrome. The currently accepted
      treatments for cholestasis in pregnancy and promising new therapeutics for the
      condition are described.

PMID- 28450277
TI  - Absence of the NOD2 protein renders epithelia more susceptible to barrier
      dysfunction due to mitochondrial dysfunction.
AB  - Irregular mitochondria structure and reduced ATP in some patients with IBD
      suggest that metabolic stress contributes to disease. Loss-of-function mutation
      in the nucleotide-binding oligomerization domain (NOD)-2 gene is a major
      susceptibility trait for IBD. Hence, we assessed if loss of NOD2 further impairs
      the epithelial barrier function instigated by disruption of mitochondrial ATP
      synthesis via the hydrogen ionophore dinitrophenol (DNP). NOD2 protein (virtually
      undetectable in epithelia under basal conditions) was increased in T84 (human
      colon cell line) cells treated with noninvasive Escherichia coli + DNP (16 h).
      Increased intracellular bacteria in wild-type (WT) and NOD2 knockdown (KD) cells
      and colonoids from NOD2-/- mice were mediated by reactive oxygen species (ROS)
      and the MAPK ERK1/2 pathways as determined by cotreatment with the antioxidant
      mitoTEMPO and the ERK inhibitor U0126: ROS was upstream of ERK1/2 activation.
      Despite increased E. coli in DNP-treated NOD2 KD compared with WT cells, there
      were no differences in the internalization of fluorescent inert beads or dead E.
      coli particles. This suggests that lack of killing in the NOD2 KD cells was
      responsible for the increased numbers of viable intracellular bacteria; a
      conclusion supported by evidence of reduced autophagy in NOD2 KD T84 epithelia.
      Thus, in a two-hit hypothesis, decreased barrier function due to dysfunctional
      mitochondrial is amplified by lack of NOD2 in transporting enterocytes:
      subsequently, greater numbers of bacteria entering the mucosa would be a
      significant inflammatory threat especially since individuals with NOD2 mutations
      have compromised macrophage and Paneth cell responses to bacteria.NEW &
      NOTEWORTHY Increased internalization of bacteria by epithelia with dysfunctional
      mitochondria (reduced ATP) is potentiated if the cells lack nucleotide-binding
      oligomerization domain 2 (NOD2), mutations in which are inflammatory bowel
      disease-susceptibility traits. Uptake of bacteria was dependent on reactive
      oxygen species and MAP-kinase activity, and the increased viable intracellular
      bacteria in NOD2-/- cells likely reflect a reduced ability to recognize and kill
      bacteria. Thus a significant barrier defect occurs with NOD2 deficiency in
      conjunction with metabolic stress that could contribute to inflammation.

PMID- 28450278
TI  - From sensing to shaping microbiota: insights into the role of NOD2 in intestinal
      homeostasis and progression of Crohn's disease.
AB  - NOD2 was the first susceptibility gene identified for Crohn's disease (CD), one
      of the major forms of inflammatory bowel disease (IBD). The field of NOD2
      research has opened up many questions critical to understanding the complexities
      of microbiota-host interactions. In addition to sensing its specific bacterial
      components as a cytosolic pattern recognition receptor, NOD2 also appears to
      shape the colonization of intestinal microbiota. Activated NOD2 triggers
      downstream signaling cascades exampled by the NF-kappaB pathway to induce
      antimicrobial activities, however, defective or loss of NOD2 functions incur a
      similarly activated inflammatory response. Additional studies have identified the
      involvement of NOD2 in protection against non-microbiota-related intestinal
      damages as well as extraintestinal infections. We survey recent molecular and
      genetic studies of NOD2-mediated bacterial sensing and immunological modulation,
      and integrate evidence to suggest a highly reciprocal but still poorly understood
      cross talk between enteric microbiota and host cells.

PMID- 28450281
TI  - A woman with intermittent heartburn.

PMID- 28450279
TI  - Autophagy upregulates (pro)renin receptor expression via reduction of P62/SQSTM1
      and activation of ERK1/2 signaling pathway in podocytes.
AB  - Autophagy plays a major role in podocytes health and disease. P62, also known as
      sequestosome-1 (SQSTM1), is a marker for autophagic activity and is required for
      the formation and degradation of ubiquitnated protein by autophagy. Knockout of
      p62 enhanced extracellular signal-regulated kinases (ERK1/2) activity. (pro)renin
      receptor (PRR) is expressed in podocytes where it contributes to the homeostasis
      of these cells. The influence of autophagy on PRR expression is unknown. We
      hypothesized that in podocytes, upregulation of autophagic activity increases PRR
      expression via reduction of p62 and stimulation of ERK1/2 signaling pathway.
      Cultured mouse podocytes were treated with the autophagy activators, rapamycin or
      Earle's balanced salt solution (EBSS), for 48 h. Both rapamycin and EBSS
      significantly decreased p62 protein levels, increased ERK1/2 activation by
      phosphorylating pTpY185/187, and increased mRNA and protein expressions of PRR.
      Utilizing confocal microscopy demonstrated that rapamycin and EBSS significantly
      decreased p62/SQSTM1 and increased PRR protein expressions. Similarly, by
      enhancing autophagic activity by transfection with autophagy-related 5 (ATG5)
      cDNA or ATG7 cDNA, results similar to those observed with rapamycin and EBSS
      treatments were produced. Inhibition of autophagic flux with bafilomycin A1
      reversed the effects of rapamycin. ERK1/2 inhibitor U0126 significantly
      attenuated mRNA and protein expressions of PRR in podocytes treated with
      rapamycin. In conclusion, upregulation of autophagy enhanced PRR expression
      through reduction of p62 and stimulation of ERK1/2 activity signaling pathway.

PMID- 28450282
TI  - Author's reply to Middeldorp and Iorio.

PMID- 28450283
TI  - Surfactant replacement therapy reduces acute lung injury and collapse induration
      related lung remodeling in the bleomycin model.
AB  - Bleomycin-induced lung injury leads to surfactant dysfunction and permanent loss
      of alveoli due to a remodeling process called collapse induration. Collapse
      induration also occurs in acute interstitial lung disease and idiopathic
      pulmonary fibrosis in humans. We hypothesized that surfactant dysfunction
      aggravates lung injury and early remodeling resulting in collapse induration
      within 7 days after lung injury. Rats received bleomycin to induce lung injury
      and either repetitive surfactant replacement therapy (SRT: 100 mg Curosurf/kg BW
      = surf group) or saline (0.9% NaCl = saline group). After 3 (D3) or 7 (D7) days,
      invasive pulmonary function tests were performed to determine tissue elastance
      (H) and static compliance (Cst). Bronchoalveolar lavage (BAL) was taken for
      surfactant function, inflammatory markers, and protein measurements. Lungs were
      fixed by vascular perfusion for design-based stereology and electron microscopic
      analyses. SRT significantly improved minimum surface tension of alveolar
      surfactant as well as H and Cst at D3 and D7. At D3 decreased inflammatory
      markers including neutrophilic granulocytes, IL-1beta, and IL-6 correlated with
      reduced BAL-protein levels after SRT. Numbers of open alveoli were significantly
      increased at D3 and D7 in SRT groups whereas at D7 there was also a significant
      reduction in septal wall thickness and parenchymal tissue volume. Septal wall
      thickness and numbers of open alveoli highly correlated with improved lung
      mechanics after SRT. In conclusion, reduction in surface tension was effective to
      stabilize alveoli linked with an attenuation of parameters of acute lung injury
      at D3 and collapse induration at D7. Hence, SRT modifies disease progression to
      collapse induration.

PMID- 28450284
TI  - EETs promote hypoxic pulmonary vasoconstriction via constrictor prostanoids.
AB  - To test the hypothesis that epoxyeicosatrienoic acids (EETs) facilitate pulmonary
      responses to hypoxia, male wild-type (WT) and soluble-epoxide hydrolase knockout
      (sEH-KO) mice, and WT mice chronically fed a sEH inhibitor (t-TUCB; 1 mg.kg-1.day
      1) were used. Right ventricular systolic pressure (RVSP) was recorded under
      control and hypoxic conditions. The control RVSP was comparable among all groups.
      However, hypoxia elicited increases in RVSP in all groups with predominance in
      sEH-KO and t-TUCB-treated mice. 14,15-EEZE (an EET antagonist) attenuated the
      hypoxia-induced greater elevation of RVSP in sEH-deficient mice, suggesting an
      EET-mediated increment. Exogenous 5,6-; 8,9-, or 14,15-EET (0.05 ng/g body wt)
      did not change RVSP in any conditions, but 11,12-EET enhanced RVSP under hypoxia.
      Isometric tension was recorded from pulmonary arteries isolated from WT and sEH
      KO mice, vessels that behaved identically in their responsiveness to vasoactive
      agents and vessel stretch. Hypoxic pulmonary vasoconstriction (HPV, expressed as
      increases in hypoxic force) was significantly greater in vessels of sEH-KO than
      WT vessels; the enhanced component was inhibited by EEZE. Treatment of WT vessels
      with 11,12-EET enhanced HPV to the same level as sEH-KO vessels, confirming EETs
      as primary players. Inhibition of cyclooxygenases (COXs) significantly enhanced
      HPV in WT vessels, but attenuated HPV in sEH-KO vessels. Blocking/inhibiting COX
      1, prostaglandin H2 (PGH2)/thromboxane A2 (TXA2) receptors and TXA synthase
      prevented the enhanced HPV in sEH-KO vessels but had no effects on WT vessels. In
      conclusion, an EET-dependent alteration in PG metabolism that favors the action
      of vasoconstrictor PGH2 and TXA2 potentiates HPV and hypoxia-induced elevation of
      RVSP in sEH-deficient mice.

PMID- 28450285
TI  - Low-dose cadmium exposure induces peribronchiolar fibrosis through site-specific
      phosphorylation of vimentin.
AB  - Exposure to cadmium (Cd) has been associated with development of chronic
      obstructive lung disease (COPD). The mechanisms and signaling pathways whereby Cd
      causes pathological peribronchiolar fibrosis, airway remodeling, and subsequent
      airflow obstruction remain unclear. We aimed to evaluate whether low-dose Cd
      exposure induces vimentin phosphorylation and Yes-associated protein 1 (YAP1)
      activation leading to peribronchiolar fibrosis and subsequent airway remodeling.
      Our data demonstrate that Cd induces myofibroblast differentiation and
      extracellular matrix (ECM) deposition around small (<2 mm in diameter) airways.
      Upon Cd exposure, alpha-smooth muscle actin (alpha-SMA) expression and the
      production of ECM proteins, including fibronectin and collagen-1, are markedly
      induced in primary human lung fibroblasts. Cd induces Smad2/3 activation and the
      translocation of both Smad2/3 and Yes-associated protein 1 (YAP1) into the
      nucleus. In parallel, Cd induces AKT and cdc2 phosphorylation and downstream
      vimentin phosphorylation at Ser39 and Ser55, respectively. AKT and cdc2
      inhibitors block Cd-induced vimentin fragmentation and secretion in association
      with inhibition of alpha-SMA expression, ECM deposition, and collagen secretion.
      Furthermore, vimentin silencing abrogates Cd-induced alpha-SMA expression and
      decreases ECM production. Vimentin-deficient mice are protected from Cd-induced
      peribronchiolar fibrosis and remodeling. These findings identify two specific
      sites on vimentin that are phosphorylated by Cd and highlight the functional
      significance of vimentin phosphorylation in YAP1/Smad3 signaling that mediates Cd
      induced peribronchiolar fibrosis and airway remodeling.

PMID- 28450287
TI  - Acupuncture upregulates G protein coupled activity in SAMP8 mice.
AB  - BACKGROUND: Transmembrane and intracellular signal transduction of G protein is
      closely related to the pathophysiology of Alzheimer's disease (AD). OBJECTIVE: To
      explore the effects of Sanjiao acupuncture on G protein signal transduction
      pathways in the pathogenesis of AD. METHODS: 36 senescence-accelerated (SAM)
      prone 8 mice were divided into three groups that remained untreated (SAMP8, n=12)
      or received Sanjiao acupuncture (SAMP8+SA, n=12) or control acupuncture
      (SAMP8+CA, n=12). An additional control group of SAM resistant 1 mice was
      included (SAMR1 group, n=12). Morris water maze tests were used to investigate
      learning and memory abilities. Immunoprecipitation and Western blotting were used
      to study expression of G protein subunits and their activities in the
      cortex/hippocampus. RESULTS: Behavioural analysis showed that acupuncture
      attenuated the severe cognitive deficits observed in untreated/CA-treated SAMP8
      mice. The findings of the G protein activation assays via immunoprecipitation and
      Western blots were that the physiologically coupled activation rate (PCAR) and
      maximal coupled activation rate (MCAR) of Galphas and Galphai were decreased in
      the cortex of SAMP8 vs SAMR1 mice. Sanjiao acupuncture induced an upregulation in
      the PCAR of Galphas and Galphai. In the hippocampus of untreated SAMP8 mice, the
      PCAR of Galphas and MCAR of both Galphas and Galphai declined, and Sanjiao
      acupuncture was associated with an upregulation in the MCAR of Galphas and
      Galphai. There were no significant differences in Galphas and Galphai expression
      between the groups. CONCLUSIONS: Sanjiao acupuncture attenuates cognitive
      deficits in a mouse model of AD via upregulation of G protein activity and
      stabilisation of the cellular signal.

PMID- 28450286
TI  - Bitter taste receptor agonists alter mitochondrial function and induce autophagy
      in airway smooth muscle cells.
AB  - Airway remodeling, including increased airway smooth muscle (ASM) mass, is a
      hallmark feature of asthma and COPD. We previously identified the expression of
      bitter taste receptors (TAS2Rs) on human ASM cells and demonstrated that known
      TAS2R agonists could promote ASM relaxation and bronchodilation and inhibit
      mitogen-induced ASM growth. In this study, we explored cellular mechanisms
      mediating the antimitogenic effect of TAS2R agonists on human ASM cells.
      Pretreatment of ASM cells with TAS2R agonists chloroquine and quinine resulted in
      inhibition of cell survival, which was largely reversed by bafilomycin A1, an
      autophagy inhibitor. Transmission electron microscope studies demonstrated the
      presence of double-membrane autophagosomes and deformed mitochondria. In ASM
      cells, TAS2R agonists decreased mitochondrial membrane potential and increased
      mitochondrial ROS and mitochondrial fragmentation. Inhibiting dynamin-like
      protein 1 (DLP1) reversed TAS2R agonist-induced mitochondrial membrane potential
      change and attenuated mitochondrial fragmentation and cell death. Furthermore,
      the expression of mitochondrial protein BCL2/adenovirus E1B 19-kDa protein
      interacting protein 3 (Bnip3) and mitochondrial localization of DLP1 were
      significantly upregulated by TAS2R agonists. More importantly, inhibiting Bnip3
      mitochondrial localization by dominant-negative Bnip3 significantly attenuated
      cell death induced by TAS2R agonist. Collectively the TAS2R agonists chloroquine
      and quinine modulate mitochondrial structure and function, resulting in ASM cell
      death. Furthermore, Bnip3 plays a central role in TAS2R agonist-induced ASM
      functional changes via a mitochondrial pathway. These findings further establish
      the cellular mechanisms of antimitogenic effects of TAS2R agonists and identify a
      novel class of receptors and pathways that can be targeted to mitigate airway
      remodeling as well as bronchoconstriction in obstructive airway diseases.

PMID- 28450288
TI  - Mark Arnold Wainberg.

PMID- 28450289
TI  - Sixty seconds on . . . a cure for dementia.

PMID- 28450290
TI  - The wider role of regulatory scientists.

PMID- 28450291
TI  - A likely urinary tract infection in a pregnant woman.

PMID- 28450292
TI  - CD44 Promotes Inflammation and Extracellular Matrix Production During
      Arteriovenous Fistula Maturation.
AB  - OBJECTIVE: Arteriovenous fistulae (AVF) remain the optimal conduit for
      hemodialysis access but continue to demonstrate poor patency and poor rates of
      maturation. We hypothesized that CD44, a widely expressed cellular adhesion
      molecule that serves as a major receptor for extracellular matrix components,
      promotes wall thickening and extracellular matrix deposition during AVF
      maturation. APPROACH AND RESULTS: AVF were created via needle puncture in wild
      type C57BL/6J and CD44 knockout mice. CD44 mRNA and protein expression was
      increased in wild-type AVF. CD44 knockout mice showed no increase in AVF wall
      thickness (8.9 versus 26.8 MUm; P=0.0114), collagen density, and hyaluronic acid
      density, but similar elastin density when compared with control AVF. CD44
      knockout mice also showed no increase in vascular cell adhesion molecule-1
      expression, intercellular adhesion molecule-1 expression, and monocyte
      chemoattractant protein-1 expression in the AVF compared with controls; there
      were also no increased M2 macrophage markers (transglutaminase-2: 81.5-fold,
      P=0.0015; interleukin-10: 7.6-fold, P=0.0450) in CD44 knockout mice. Delivery of
      monocyte chemoattractant protein-1 to CD44 knockout mice rescued the phenotype
      with thicker AVF walls (27.2 versus 14.7 MUm; P=0.0306), increased collagen
      density (2.4-fold; P=0.0432), and increased number of M2 macrophages (2.1-fold;
      P=0.0335). CONCLUSIONS: CD44 promotes accumulation of M2 macrophages,
      extracellular matrix deposition, and wall thickening during AVF maturation. These
      data show the association of M2 macrophages with wall thickening during AVF
      maturation and suggest that enhancing CD44 activity may be a strategy to increase
      AVF maturation.

PMID- 28450293
TI  - Extracellular Cyclophilin A, Especially Acetylated, Causes Pulmonary Hypertension
      by Stimulating Endothelial Apoptosis, Redox Stress, and Inflammation.
AB  - OBJECTIVE: Oxidative stress and inflammation play key roles in the development of
      pulmonary arterial hypertension (PAH). Cyclophilin A (CypA) is secreted in
      response to oxidative stress and promotes inflammation and cardiovascular
      disease. Endothelial cell (EC) dysfunction is an early event in the pathogenesis
      of PAH. We evaluated the role of extracellular CypA in PAH and compared the
      effects of acetylated CypA (AcK-CypA, increased by oxidative stress) and CypA on
      EC dysfunction. APPROACH AND RESULTS: In transgenic mice that express high levels
      of CypA in EC specifically, a PAH phenotype was observed at 3 months including
      increased right ventricular systolic pressure, alpha-smooth muscle actin
      expression in small arterioles, and CD45-positive cells in the lungs. Mechanistic
      analysis using cultured mouse pulmonary microvascular EC and human pulmonary
      microvascular EC showed that extracellular CypA and AcK-CypA stimulated EC
      inflammatory signals: increased VCAM1 (vascular cell adhesion molecule 1) and
      ICAM1 (intercellular adhesion molecule 1), phosphorylation of p65, and
      degradation of IkB. Extracellular CypA and AcK-CypA increased EC apoptosis
      measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)
      staining, Apo-ONE assay, and caspase 3 cleavage. Oxidative stress stimulated CypA
      and AcK-CypA secretion, which further promoted EC oxidative stress. AcK-CypA,
      compared with CypA, stimulated greater increases in apoptosis, inflammation, and
      oxidative stress. MM284, a specific inhibitor of extracellular CypA, attenuated
      EC apoptosis induced by CypA and AcK-CypA. CONCLUSIONS: EC-derived CypA
      (especially AcK-CypA) causes PAH by a presumptive mechanism involving increased
      EC apoptosis, inflammation, and oxidative stress. Our results suggest that
      inhibiting secreted extracellular CypA is a novel therapeutic approach for PAH.

PMID- 28450294
TI  - Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous
      Thrombosis.
AB  - OBJECTIVE: Coagulation and inflammation are inter-related. Gas6 (growth arrest
      specific 6) promotes venous thrombosis and participates to inflammation through
      endothelial-innate immune cell interactions. Innate immune cells can provide the
      initiating stimulus for venous thrombus development. We hypothesize that Gas6
      promotes monocyte recruitment during venous thrombosis. APPROACH AND RESULTS:
      Deep venous thrombosis was induced in wild-type and Gas6-deficient (-/-) mice
      using 5% FeCl3 and flow reduction in the inferior vena cava. Total monocyte
      depletion was achieved by injection of clodronate before deep venous thrombosis.
      Inflammatory monocytes were depleted using an anti-C-C chemokine receptor type 2
      (CCR2) antibody. Similarly, injection of an anti-chemokine ligand 2 (CCL2)
      antibody induced CCL2 depletion. Flow cytometry and immunofluorescence were used
      to characterize the monocytes recruited to the thrombus. In vivo, absence of Gas6
      was associated with a reduction of monocyte recruitment in both deep venous
      thrombosis models. Global monocyte depletion by clodronate leads to smaller
      thrombi in wild-type mice. Compared with wild type, the thrombi from Gas6-/- mice
      contain less inflammatory (CCR2hiCX3CR1lo) monocytes, consistent with a Gas6
      dependent recruitment of this monocyte subset. Correspondingly, selective
      depletion of CCR2hiCX3CR1lo monocytes reduced the formation of venous thrombi in
      wild-type mice demonstrating a predominant role of the inflammatory monocytes in
      thrombosis. In vitro, the expression of both CCR2 and CCL2 were Gas6 dependent in
      monocytes and endothelial cells, respectively, impacting monocyte migration.
      Moreover, Gas6-dependent CCL2 expression and monocyte migration were mediated via
      JNK (c-Jun N-terminal kinase). CONCLUSIONS: This study demonstrates that Gas6
      specifically promotes the recruitment of inflammatory CCR2hiCX3CR1lo monocytes
      through the regulation of both CCR2 and CCL2 during deep venous thrombosis.

PMID- 28450295
TI  - Statin Pretreatment and Microembolic Signals in Large Artery Atherosclerosis.
AB  - OBJECTIVE: Although statin pretreatment (SP) is associated with better outcomes
      in patients with acute cerebral ischemia after an ischemic stroke/transient
      ischemic attack, data on the underlying mechanism of this beneficial effect are
      limited. APPROACH AND RESULTS: We sought to evaluate the potential association
      between SP and microembolic signal (MES) burden in acute cerebral ischemia
      because of large artery atherosclerosis (LAA). We prospectively evaluated
      consecutive patients with first-ever acute cerebral ischemia because of LAA in 3
      tertiary stroke centers over a 2-year period. All patients underwent continuous 1
      hour transcranial Doppler monitoring of the relevant vessel at baseline (<=24
      hours). SP was recorded and dichotomized as high dose or low-to-moderate dose. SP
      was documented in 43 (41%) of 106 LAA patients (mean age, 65.4+/-10.3 years; 72%
      men; low-to-moderate dose, 32%; high dose, 8%). There was a significant (P=0.022)
      dose-dependent effect between SP and MES prevalence: no SP (37%), SP with low-to
      moderate dose (18%), and SP with high dose (0%). Similarly, a significant
      (P=0.045) dose-dependent effect was documented between SP and MES burden: no SP
      (1.1+/-1.8), SP with low-to-moderate dose (0.7+/-1.6), and SP with high dose (0+/
      0). In multivariable logistic regression analysis adjusting for demographics,
      vascular risk factors, location of LAA, stroke severity, and other prevention
      therapies, SP was associated with lower likelihood of MES presence (odds ratio,
      0.29; 95% confidence interval, 0.09-0.92; P=0.036). In addition, SP was found
      also to be independently related to higher odds of functional improvement (common
      odds ratio, 3.33; 95% confidence interval, 1.07-10.0; P=0.037). CONCLUSIONS: We
      found that SP in patients with acute LAA is related with reduced MES presence and
      lower MES burden with an apparently dose-dependent association.

PMID- 28450297
TI  - Association Between Carotid Atherosclerotic Plaque Calcification and Intraplaque
      Hemorrhage: A Magnetic Resonance Imaging Study.
AB  - OBJECTIVE: Carotid intraplaque hemorrhage (IPH) is associated with cardiovascular
      events. Calcification, which frequently accompanies IPH, may play a role in IPH
      occurrence. In this study, we aimed to investigate the associations between
      calcification characteristics and IPH in carotid plaques. APPROACH AND RESULTS:
      One hundred seventeen patients with cerebrovascular symptoms and carotid plaques
      detected by ultrasound were recruited and underwent multicontrast magnetic
      resonance imaging. Advanced carotid plaques with composition measured by magnetic
      resonance imaging were included in the analysis. Carotid calcifications were
      divided into the following categories: surface, mixed, and deep calcification.
      They were also classified into single and multiple calcifications according to
      quantity. Logistic regression models utilizing generalized estimating equations
      were performed to evaluate the relationship between calcification and IPH. Of 117
      subjects, 85 with 142 plaques were included in the final analysis, whereas 32
      were excluded because of lack of plaque compositions. Of the 142 plaques, 40
      (28.2%) had IPH. Plaques with IPH showed greater prevalence of calcification than
      those without (87.5% versus 55.9%; P=0.005). After adjusting for age, low-density
      lipoprotein, maximum wall thickness, and maximum soft plaque thickness, multiple
      calcifications (odd ratio, 10.1; 95% confidence interval, 3.3-30.4), surface
      calcification (odd ratio, 29.4; 95% confidence interval, 4.1-210.8), and mixed
      calcifications (odd ratio, 27.9; 95% confidence interval, 7.3-107.1) were found
      to be strongly associated with the presence of IPH (all P<0.05). CONCLUSIONS:
      Surface calcification and multiple calcifications in carotid atherosclerotic
      plaques are independently associated with the presence of IPH, suggesting that
      both quantity and location of calcification may play important roles in the
      occurrence of IPH. These findings may provide novel insights for understanding
      mechanisms of IPH.

PMID- 28450298
TI  - Molecular Imaging of Atherothrombotic Diseases: Seeing Is Believing.
AB  - Molecular imaging, with major advances in the development of both innovative
      targeted contrast agents/particles and radiotracers, as well as various imaging
      technologies, is a fascinating, rapidly growing field with many preclinical and
      clinical applications, particularly for personalized medicine. Thrombosis in
      either the venous or the arterial system, the latter typically caused by rupture
      of unstable atherosclerotic plaques, is a major determinant of mortality and
      morbidity in patients. However, imaging of the various thrombotic complications
      and the identification of plaques that are prone to rupture are at best indirect,
      mostly unreliable, or not available at all. The development of molecular imaging
      toward diagnosis and prevention of thrombotic disease holds promise for major
      advance in this clinically important field. Here, we review the medical need and
      clinical importance of direct molecular imaging of thrombi and unstable
      atherosclerotic plaques that are prone to rupture, thereby causing thrombotic
      complications such as myocardial infarction and ischemic stroke. We
      systematically compare the advantages/disadvantages of the various molecular
      imaging modalities, including X-ray computed tomography, magnetic resonance
      imaging, positron emission tomography, single-photon emission computed
      tomography, fluorescence imaging, and ultrasound. We further systematically
      discuss molecular targets specific for thrombi and those characterizing unstable,
      potentially thrombogenic atherosclerotic plaques. Finally, we provide examples
      for first theranostic approaches in thrombosis, combining diagnosis, targeted
      therapy, and monitoring of therapeutic success or failure. Overall, molecular
      imaging is a rapidly advancing field that holds promise of major benefits to many
      patients with atherothrombotic diseases.

PMID- 28450296
TI  - Endoglin Mediates Vascular Maturation by Promoting Vascular Smooth Muscle Cell
      Migration and Spreading.
AB  - OBJECTIVE: Endoglin, a transforming growth factor-beta superfamily coreceptor, is
      predominantly expressed in endothelial cells and has essential roles in vascular
      development. However, whether endoglin is also expressed in vascular smooth
      muscle cells (VSMCs), especially in vivo, remains controversial. Furthermore, the
      roles of endoglin in VSMC biology remain largely unknown. Our objective was to
      examine the expression and determine the function of endoglin in VSMCs during
      angiogenesis. APPROACH AND RESULTS: Here, we determine that endoglin is robustly
      expressed in VSMCs. Using CRISPR/CAS9 knockout and short hairpin RNA knockdown in
      the VSMC/endothelial coculture model system, we determine that endoglin in VSMCs,
      but not in endothelial cells, promotes VSMCs recruitment by the endothelial cells
      both in vitro and in vivo. Using an unbiased bioinformatics analysis of RNA
      sequencing data and further study, we determine that, mechanistically, endoglin
      mediates VSMC recruitment by promoting VSMC migration and spreading on
      endothelial cells via increasing integrin/FAK pathway signaling, whereas endoglin
      has minimal effects on VSMC adhesion to endothelial cells. In addition, we
      further determine that loss of endoglin in VSMCs inhibits VSMC recruitment in
      vivo. CONCLUSIONS: These studies demonstrate that endoglin has an important role
      in VSMC recruitment and blood vessel maturation during angiogenesis and also
      provide novel insights into how discordant endoglin function in endothelial and
      VSMCs may regulate vascular maturation and angiogenesis.

PMID- 28450299
TI  - Circadian Control of Inflammatory Processes in Atherosclerosis and Its
      Complications.
AB  - Physiological cardiovascular functions show daily diurnal variations, which are
      synchronized by intrinsic molecular clocks and environment-driven cues. The
      clinical manifestation of cardiovascular disease also exhibits diurnal variation,
      with an increased incidence in the early morning. This coincides with circadian
      oscillations of circulating parameters, such as hormones and leukocyte counts. We
      are just at the beginning of understanding how circadian rhythms of immune
      functions are related to cardiovascular disease progression and outcome after an
      acute ischemic event. Here, we briefly summarize clinical data on oscillations of
      circulating inflammatory parameters, as well as experimental evidences for the
      role of circadian clocks in atherosclerosis, postmyocardial infarction
      inflammatory responses, and cardiac healing.

PMID- 28450300
TI  - Plain cigarette packs may cut number of smokers, evidence review finds.

PMID- 28450304
TI  - Politicians must commit to increased investment in NHS.

PMID- 28450301
TI  - Neuron-specific caveolin-1 overexpression improves motor function and preserves
      memory in mice subjected to brain trauma.
AB  - Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin
      (Cav) organize progrowth receptors, and, when overexpressed specifically in
      neurons, Cav-1 augments neuronal signaling and growth and improves cognitive
      function in adult and aged mice; however, whether neuronal Cav-1 overexpression
      can preserve motor and cognitive function in the brain trauma setting is unknown.
      Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse
      [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical
      impact model of brain trauma and measured biochemical, anatomic, and behavioral
      changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and
      membrane/lipid raft localization of postsynaptic density protein 95, NMDA
      receptor, and tropomyosin receptor kinase B. When subjected to a controlled
      cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent
      fear learning and memory, improved motor function recovery, and decreased brain
      lesion volume compared with wild-type controls. Neuron-targeted overexpression of
      Cav-1 in the adult brain prevents hippocampus-dependent learning and memory
      deficits, restores motor function after brain trauma, and decreases brain lesion
      size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can
      be used as a novel therapeutic strategy to restore brain function and prevent
      trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W.,
      Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J.,
      Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron
      specific caveolin-1 overexpression improves motor function and preserves memory
      in mice subjected to brain trauma.

PMID- 28450303
TI  - Journey of particulate pollution in body is mapped in study.

PMID- 28450305
TI  - MECHANISMS IN ENDOCRINOLOGY: Update on pathogenesis of primary adrenal
      insufficiency: beyond steroid enzyme deficiency and autoimmune adrenal
      destruction.
AB  - Primary adrenal insufficiency (PAI) is potentially life threatening, but rare. In
      children, genetic defects prevail whereas adults suffer more often from acquired
      forms of PAI. The spectrum of genetic defects has increased in recent years with
      the use of next-generation sequencing methods and now has reached far beyond
      genetic defects in all known enzymes of adrenal steroidogenesis. Cofactor
      disorders such as P450 oxidoreductase (POR) deficiency manifesting as a complex
      form of congenital adrenal hyperplasia with a broad clinical phenotype have come
      to the fore. In patients with isolated familial glucocorticoid deficiency (FGD),
      in which no mutations in the genes for the ACTH receptor (MC2R) or its accessory
      protein MRAP have been found, non-classic steroidogenic acute regulatory protein
      (StAR) and CYP11A1 mutations have been described; and more recently novel
      mutations in genes such as nicotinamide nucleotide transhydrogenase (NNT) and
      thioredoxin reductase 2 (TRXR2) involved in the maintenance of the mitochondrial
      redox potential and generation of NADPH important for steroidogenesis and ROS
      detoxication have been discovered. In addition, whole exome sequencing approach
      also solved the genetics of some syndromic forms of PAI including IMAGe syndrome
      (CDKN1C), Irish traveler syndrome (MCM4), MIRAGE syndrome (SAMD9); and most
      recently a syndrome combining FGD with steroid-resistant nephrotic syndrome and
      ichthyosis caused by mutations in the gene for sphingosine-1-phosphate lyase 1
      (SGPL1). This review intends do give an update on novel genetic forms of PAI and
      their suggested mechanism of disease. It also advocates for advanced genetic work
      up of PAI (especially in children) to reach a specific diagnosis for better
      counseling and treatment.

PMID- 28450307
TI  - Severe postpartum headache.

PMID- 28450308
TI  - What role will the NHS play in the 2017 election?

PMID- 28450306
TI  - Osteoblasts support megakaryopoiesis through production of interleukin-9.
AB  - Severe thrombocytopenia is a significant challenge in patients undergoing
      myelosuppressive chemotherapy for malignancies. Understanding the biology of
      platelet-producing megakaryocytes development in the bone marrow microenvironment
      may facilitate the development of novel therapies to stimulate platelet
      production and prevent thrombocytopenia. We report here that osteoblasts
      supported megakaryopoiesis by secreting interleukin-9 (IL-9), which stimulated IL
      9 receptor (IL-9R)/Stat3 signaling in promoting megakaryopoiesis. IL-9 production
      in osteoblasts was negatively regulated by the mechanistic target of rapamycin
      complex 1 (mTORC1) signaling in a NF-kappaB-dependent manner. Constitutive
      activation of mTORC1 inhibited IL-9 production in osteoblasts and suppressed
      megakaryocytic cells expansion, whereas mTORC1 inactivation increased IL-9
      production and enhanced megakaryocyte and platelet numbers in mice. In mouse
      models, we showed that IL-9 administration stimulated megakaryopoiesis, whereas
      neutralizing endogenous IL-9 or IL-9R depletion inhibited the process.
      Importantly, we found that low doses of IL-9 efficiently prevented chemotherapy
      induced thrombocytopenia (CIT) and accelerated platelet recovery after CIT. These
      data indicate that IL-9 is an essential regulator of megakaryopoiesis and a
      promising therapeutic agent for treatment of thrombocytopenia such as CIT.

PMID- 28450310
TI  - Response to: 'The time has come to revisit alternative interpretations of data
      underlying the EULAR management recommendations for rheumatoid arthritis' by
      Pirila et al.

PMID- 28450309
TI  - Decreasing Exposure to Radiation, Surgical Risk, and Costs for Pediatric
      Complicated Pneumonia: A Guideline Evaluation.
AB  - OBJECTIVES: This report describes the creation and successful implementation of a
      complicated pneumonia care algorithm at our institution. Outcomes are measured
      for specific goals of the algorithm: to decrease radiation exposure, surgical
      risk, and patient charges without adversely affecting clinical outcomes. METHODS:
      We describe steps involved in algorithm creation and implementation at our
      institution. To depict outcomes of the algorithm, we completed a retrospective
      cohort study of hospitalized pediatric patients with a diagnosis of complicated
      pneumonia at a single institution between January 2010 and April 2016 who met
      criteria for the algorithm. Charts were manually reviewed and data were analyzed
      via Wilcoxon rank sum, chi2, and Fisher's exact tests. RESULTS: Throughout the
      algorithm creation process, our institution began to see a change in practice. We
      saw a statistically significant decrease in the number of patients who underwent
      a chest computed tomography scan and an increase in patients who underwent a
      chest ultrasound (P < .001). We also saw an increase in the use of chest tube
      placement with fibrinolytics and a decrease in the use of video-assisted
      thoracoscopic surgery as the initial chest procedure (P <= .001) after algorithm
      implementation. These interventions reduced related charges without significantly
      affecting length of stay, readmission rate, or other variables studied.
      CONCLUSIONS: The collaborative creation and introduction of an algorithm for the
      management of complicated pneumonia at our institution, combined with an effort
      among physicians to incorporate evidence-based clinical care into practice, led
      to reduced radiation exposure, surgical risk, and cost to patient.

PMID- 28450311
TI  - Alternative interpretation of data for recommendations on how to manage
      rheumatoid arthritis.

PMID- 28450312
TI  - Long-term outcome is better when a methotrexate-based treatment strategy is
      combined with 10 mg prednisone daily: follow-up after the second Computer
      Assisted Management in Early Rheumatoid Arthritis trial.
AB  - OBJECTIVES: In the second Computer-Assisted Management in Early Rheumatoid
      Arthritis trial, patients had started with methotrexate and 10 mg prednisone
      (MTX+pred) or placebo (MTX+plac). After the trial, prednisone was tapered and
      stopped, if possible. The objective was to compare, during the post-trial follow
      up between the two former strategy groups, initiation of the first biological
      disease-modifying antirheumatic drug (bDMARD), radiographic outcome and onset of
      glucocorticoid (GC)-related comorbidities. METHODS: Data on prednisone and bDMARD
      use and onset of GC-related comorbidities were collected retrospectively.
      Sharp/van der Heijde scoring was performed. Data were analysed using Fisher's
      exact and Mann-Whitney U tests. RESULTS: Of 218 patients post-trial follow-up
      data were available. The maximum follow-up time was 11.8 years. Fewer patients
      initiated a first bDMARD in the former MTX+pred compared with the former MTX+plac
      strategy group: 31% vs 50%, p=0.003. At the 2 year post-trial follow-up, the
      median erosion score was significantly lower in the former MTX+pred versus former
      MTX+plac strategy group: 0 (range 0-0) versus 0 (0-2), p=0.002. No significant
      differences between the former strategy groups in the onset of GC-related
      comorbidities during the post-trial follow-up were found. CONCLUSION: Addition of
      10 mg prednisone daily to an MTX-based treatment strategy in early rheumatoid
      arthritis results in a lower initiation rate of a first bDMARD and significantly
      better radiographic outcomes, yet does not result in more GC-related
      comorbidities.

PMID- 28450314
TI  - Better Care Fund no more than a "ruse" to cover up funding pressures, say MPs.

PMID- 28450313
TI  - Enteric-coated mycophenolate sodium versus azathioprine in patients with active
      systemic lupus erythematosus: a randomised clinical trial.
AB  - OBJECTIVE: To compare the efficacy and safety of enteric-coated mycophenolate
      sodium (EC-MPS) versus azathioprine (AZA) in patients with active systemic lupus
      erythematosus (SLE) disease. METHODS: A multicentre, 24-month, superiority, open
      label, randomised controlled trial (NCT01112215) was conducted with 240 patients
      (120 per arm) receiving either EC-MPS (target dose: 1440 mg/day) or AZA (target
      dose: 2 mg/kg/day) in addition to prednisone and/or antimalarials. The primary
      endpoint was the proportion of patients achieving clinical remission, assessed by
      SLE Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment
      Group (BILAG), at 3 and 24 months. Secondary endpoints included time to clinical
      remission, BILAG A and B flare rates, time to flare, corticosteroid reduction and
      adverse events (AEs). RESULTS: Proportion of patients achieving clinical
      remission (clinical SLEDAI=0) was higher in the EC-MPS group at 3 (32.5% vs
      19.2%; treatment difference, 13.3 (CI 2.3 to 24), p=0.034) and 24 months (71.2%
      vs 48.3%; treatment difference, 22.9 (CI 10.4 to 34.4), p<0.001). EC-MPS was
      superior with respect to time to clinical remission (HR 1.43; 95% CI 1.07 to
      1.91; p=0.017). BILAG A/B and B flares occurred more frequently in the AZA group
      (71.7% vs 50%, p=0.001 and 21.67% vs 8.3%, p=0.004, respectively). EC-MPS was
      superior with respect to time to first BILAG A/B (HR 1.81; 95% CI 1.3 to 2.56;
      p=0.0004) and BILAG A flare (HR 2.84; 95% CI 1.37 to 5.89; p=0.003). AEs were
      similar in both groups except for leucopenia that occurred more frequently with
      AZA. CONCLUSIONS: EC-MPS was superior to AZA in treating SLE and preventing
      further relapses. TRIAL REGISTRATION NUMBER: NCT01112215; Results.

PMID- 28450315
TI  - miRNA-mRNA network involved in folliculogenesis interactome: systems biology
      approach.
AB  - At later phases of folliculogenesis, the mammalian ovarian follicle contains
      layers of granulosa cells surrounding an antral cavity. To better understand the
      molecular basis of follicular growth and granulosa cell maturation, we study
      transcriptome profiling of granulosa cells from small (<5 mm) and large (>10 mm)
      bovine follicles using simultaneous method of Affymetrix microarrays (24,128
      probe sets) and RNA-Seq data sets. This study proposes a computational method to
      discover the functional miRNA-mRNA regulatory modules, that is, groups of miRNAs
      and their target mRNAs that are believed to take part cooperatively in post
      transcriptional gene regulation under specific conditions. The reconstructed
      network was named Integrated miRNA-mRNA Bipartite Network. 277 genes and 6 key
      modules were disclosed through clustering for mRNA master list. The 66 genes are
      among the genes that belong to at least two modules. All these genes, being
      involved in at least one of the phenomena, namely cell survival, proliferation,
      metastasis and apoptosis, have an overexpression pattern (P < 0.01). For miRNA
      master list, a total of 172 sequences were differentially expressed (P < 0.01)
      between dominant (large) and each of subordinate (small) follicles. Within the
      follicle, these miRNAs were predominantly expressed in mural granulosa cells.
      Finally, predicted and validated targets of these miRNAs enriched in dominant
      (large) follicles were identified, which are mapped to signaling pathways
      involved in follicular cell proliferation, steroidogenesis, PI3K/AKT/mTOR and
      Ras/Raf/MEK/ERK. The identification of miRNAs and their target mRNAs and the
      construction of their regulatory networks may give new insights into biological
      procedures.

PMID- 28450316
TI  - The combined use of kartogenin and platelet-rich plasma promotes fibrocartilage
      formation in the wounded rat Achilles tendon entheses.
AB  - OBJECTIVES: After an injury, the biological reattachment of tendon to bone is a
      challenge because healing takes place between a soft (tendon) and a hard (bone)
      tissue. Even after healing, the transition zone in the enthesis is not completely
      regenerated, making it susceptible to re-injury. In this study, we aimed to
      regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of
      kartogenin (KGN) and platelet-rich plasma (PRP). METHODS: Wounds created in rat
      ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN
      PRP); PRP; or saline (control), followed by histological and immunochemical
      analyses, and mechanical testing of the rat ATEs after three months of healing.
      RESULTS: Histological analysis showed well organised arrangement of collagen
      fibres and proteoglycan formation in the wounded ATEs in the KGN-PRP group.
      Furthermore, immunohistochemical analysis revealed fibrocartilage formation in
      the KGN-PRP-treated ATEs, evidenced by the presence of both collagen I and II in
      the healed ATE. Larger positively stained collagen III areas were found in both
      PRP and saline groups than those in the KGN-PRP group. Chondrocyte-related genes,
      SOX9 and collagen II, and tenocyte-related genes, collagen I and scleraxis (SCX),
      were also upregulated by KGN-PRP. Moreover, mechanical testing results showed
      higher ultimate tensile strength in the KGN-PRP group than in the saline control
      group. In contrast, PRP treatment appeared to have healed the injured ATE but
      induced no apparent formation of fibrocartilage. The saline-treated group showed
      poor healing without fibrocartilage tissue formation in the ATEs. CONCLUSIONS:
      Our results show that injection of KGN-PRP induces fibrocartilage formation in
      the wounded rat ATEs. Hence, KGN-PRP may be a clinically relevant, biological
      approach to regenerate injured enthesis effectively.Cite this article: J. Zhang,
      T. Yuan, N. Zheng, Y. Zhou, M. V. Hogan, J. H-C. Wang. The combined use of
      kartogenin and platelet-rich plasma promotes fibrocartilage formation in the
      wounded rat Achilles tendon entheses. Bone Joint Res 2017;6:231-244. DOI:
      10.1302/2046-3758.64.BJR-2017-0268.R1.

PMID- 28450317
TI  - The segment-dependent changes in lumbar intervertebral space height during
      flexion-extension motion.
AB  - OBJECTIVES: Many studies have investigated the kinematics of the lumbar spine and
      the morphological features of the lumbar discs. However, the segment-dependent
      immediate changes of the lumbar intervertebral space height during flexion
      extension motion are still unclear. This study examined the changes of
      intervertebral space height during flexion-extension motion of lumbar specimens.
      METHODS: First, we validated the accuracy and repeatability of a custom-made
      mechanical loading equipment set-up. Eight lumbar specimens underwent CT scanning
      in flexion, neural, and extension positions by using the equipment set-up. The
      changes in the disc height and distance between adjacent two pedicle screw entry
      points (DASEP) of the posterior approach at different lumbar levels (L3/4, L4/5
      and L5/S1) were examined on three-dimensional lumbar models, which were
      reconstructed from the CT images. RESULTS: All the vertebral motion segments
      (L3/4, L4/5 and L5/S1) had greater changes in disc height and DASEP from neutral
      to flexion than from neutral to extension. The change in anterior disc height
      gradually increased from upper to lower levels, from neutral to flexion. The
      changes in anterior and posterior disc heights were similar at the L4/5 level
      from neutral to extension, but the changes in anterior disc height were
      significantly greater than those in posterior disc height at the L3/4 and L5/S1
      levels, from neutral to extension. CONCLUSIONS: The lumbar motion segment showed
      level-specific changes in disc height and DASEP. The data may be helpful in
      understanding the physiologic dynamic characteristics of the lumbar spine and in
      optimising the parameters of lumbar surgical instruments.Cite this article: M.
      Fu, Q. Ye, C. Jiang, L. Qian, D. Xu, Y. Wang, P. Sun, J. Ouyang. The segment
      dependent changes in lumbar intervertebral space height during flexion-extension
      motion. Bone Joint Res 2017;6:245-252. DOI: 10.1302/2046-3758.64.BJR-2016
      0245.R1.

PMID- 28450318
TI  - The protective role of nitric oxide-dependent innate immunosuppression in the
      early stage of cartilage damage in rats: Role of nitric oxide in cartilage
      damage.
AB  - OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis, affecting
      approximately 15% of the human population. Recently, increased concentration of
      nitric oxide in serum and synovial fluid in patients with OA has been observed.
      However, the exact role of nitric oxide in the initiation of OA has not been
      elucidated. The aim of the present study was to investigate the role of nitric
      oxide in innate immune regulation during OA initiation in rats. METHODS: Rat OA
      was induced by performing meniscectomy surgery while cartilage samples were
      collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were
      determined by using enzyme-linked immunosorbent assay, while other proteins were
      assessed by using Western blot RESULTS: In the time course of the study, nitric
      oxide was increased seven and 14 days after OA induction. Pro-inflammatory
      cytokines including tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta,
      and IL-6 were decreased. L-NG-Nitroarginine methyl ester (L-NAME, a non-specific
      nitric oxide synthase inhibitor) significantly decreased cartilage nitric oxide
      and blocked immune suppression. Further, L-NAME decreased Matrix
      metalloproteinase (MMPs) and increased tissue inhibitor of metalloproteinase
      (TIMP) expression in meniscectomised rats. CONCLUSION: Nitric oxide-dependent
      innate immune suppression protects cartilage from damage in the early stages of
      OA initiation in rats.Cite this article: C-C. Hsu, C-L. Lin, I-M. Jou, P-H. Wang,
      J-S. Lee. The protective role of nitric oxide-dependent innate immunosuppression
      in the early stage of cartilage damage in rats: Role of nitric oxide in ca
      rtilage da mage. Bone Joint Res 2017;6:253-258. DOI: 10.1302/2046-3758.64.BJJ
      2016-0161.R1.

PMID- 28450319
TI  - The More It Changes ...

PMID- 28450320
TI  - General practice and the Sustainability and Transformation imperatives.

PMID- 28450321
TI  - Speaking up in the NHS in England: the work of the National Guardian and NHS
      England.

PMID- 28450322
TI  - The state of social care: the reality of a fragmented system.

PMID- 28450323
TI  - Detecting liver disease in primary care: are we ready for change?

PMID- 28450324
TI  - MUS: actually we can and should explain such symptoms.

PMID- 28450325
TI  - Medically unexplained symptoms: continuing challenges for primary care.

PMID- 28450326
TI  - Medically unexplained symptoms.

PMID- 28450327
TI  - Viewpoint: Embracing uncertainty.

PMID- 28450328
TI  - Frailty as illness and the cultural landscape.

PMID- 28450329
TI  - A quantum perspective: an analogy for a GP worldview?

PMID- 28450330
TI  - The fate of the frog: doctors as instruments of the state.

PMID- 28450331
TI  - Yonder: Fibromyalgia, dentists, cancer survivorship, and chocolate.

PMID- 28450333
TI  - Grieving with Buffy 20 years on.

PMID- 28450332
TI  - Bad Medicine: Catastrophe thinking.

PMID- 28450334
TI  - BJGP Library: The Millstone: Grit Smoothed Off After 50 Years.

PMID- 28450335
TI  - Books: The 10-Minute Clincial Assessment: A Systematic and Easy to Follow Guide -
      From Hirsutism to Heart Failure to Self-Harm.

PMID- 28450336
TI  - Books: Insane Clown President: Dispatches from the American Circus: Hand in
      Glove.

PMID- 28450337
TI  - Books: Evaluative research methods. Managing the complexities of judgment in the
      field: Evaluation for Social Justice.

PMID- 28450338
TI  - Population health.

PMID- 28450339
TI  - The Family Doctor Charter: 50 years on.

PMID- 28450340
TI  - Publishing qualitative research in medical journals.

PMID- 28450341
TI  - Word cloud analysis of the BJGP: 5 years on.

PMID- 28450342
TI  - The Confidential Enquiry into Maternal Deaths 2015: lessons for GPs.

PMID- 28450343
TI  - Clinical assessment and management of multimorbidity: NICE guideline.

PMID- 28450344
TI  - Chronic obstructive pulmonary disease and comorbidities: a large cross-sectional
      study in primary care.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common, and a major
      cause of morbidity and mortality worldwide. Recent studies suggest that
      comorbidities of COPD increase the risk of hospitalisation, polypharmacy, and
      mortality, but their estimated prevalence varies widely in the literature. AIM:
      To evaluate the prevalence of 38 physical and mental health comorbidities in
      people with COPD, and compare findings with those for people without COPD in a
      large nationally representative dataset. DESIGN AND SETTING: A cross-sectional
      data analysis on 1 272 685 adults in Scotland from 314 primary care practices.
      METHOD: Data on COPD, along with 31 physical and seven mental health
      comorbidities, were extracted. The prevalence of comorbidities was compared
      between people who did, and did not, have COPD, standardised by age, sex, and
      socioeconomic deprivation. RESULTS: From the total sample, 51 928 patients had
      COPD (4.1%). Of these, 86.0% had at least one comorbidity, compared with 48.9% of
      people without COPD. Of those with COPD, 22.3% had >=5 comorbid conditions
      compared with 4.9% of those who did not have COPD (adjusted odds ratio 2.63, 95%
      confidence interval = 2.56 to 2.70). In total, 29 of the 31 physical conditions
      and six of the seven mental health conditions were statistically significantly
      more prevalent in people who had COPD than those who did not. CONCLUSION:
      Patients with COPD have extensive associated comorbidities. There is a real need
      for guidelines and health care to reflect this complexity, including how to
      detect those common comorbidities that relate to both physical and mental health,
      and how best to manage them. Primary care, which is unique in terms of offering
      expert generalist care, is best placed to provide this integrated approach.

PMID- 28450346
TI  - Rachel Clarke: Jeremy Hunt, I'm after you.

PMID- 28450345
TI  - The Friends and Family Test in general practice in England: a qualitative study
      of the views of staff and patients.
AB  - BACKGROUND: The Friends and Family Test (FFT) was introduced into general
      practices in England in 2015 to provide staff with information on patients' views
      of their experience of care. AIM: To examine the views of practice staff and
      patients of the FFT, how the results are used, and to recommend improvements.
      DESIGN AND SETTING: A qualitative study of a national representative sample of 42
      general practices. METHOD: Semi-structured interviews with 43 clinicians, 48
      practice managers, and 27 patient representatives. Interviews were audiotaped,
      transcribed, and analysed thematically. RESULTS: Although the FFT imposed little
      extra work on practices, it was judged to provide little additional insight over
      existing methods and to have had minimal impact on improving quality. Staff
      lacked confidence in the accuracy of the results given the lack of a
      representative sample and the risk of bias. The FFT question was judged to be
      inappropriate as in many areas there was no alternative practice for patients to
      choose, patients' individual needs would not be the same as those of their
      friends and relatives, and an overall assessment failed to identify any specific
      aspects of good- or poor-quality care. Despite being intended to support local
      quality improvement, there was widespread unease about the FFT, with many
      responders perceiving it as a tool for national bodies to monitor general
      practices. CONCLUSION: If the use of a single-item questionnaire is to continue,
      changes should be made to the wording. It should be focused on stimulating local
      quality improvement, and practice staff should be supported to use the results
      effectively.

PMID- 28450347
TI  - Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in
      Athletes.
AB  - BACKGROUND: Higher levels of physical activity are associated with a lower risk
      of cardiovascular events. Nevertheless, there is debate on the dose-response
      relationship of exercise and cardiovascular disease outcomes and whether high
      volumes of exercise may accelerate coronary atherosclerosis. We aimed to
      determine the relationship between lifelong exercise volumes and coronary
      atherosclerosis. METHODS: Middle-aged men engaged in competitive or recreational
      leisure sports underwent a noncontrast and contrast-enhanced computed tomography
      scan to assess coronary artery calcification (CAC) and plaque characteristics.
      Participants reported lifelong exercise history patterns. Exercise volumes were
      multiplied by metabolic equivalent of task (MET) scores to calculate MET-minutes
      per week. Participants' activity was categorized as <1000, 1000 to 2000, or >2000
      MET-min/wk. RESULTS: A total of 284 men (age, 55+/-7 years) were included. CAC
      was present in 150 of 284 participants (53%) with a median CAC score of 35.8
      (interquartile range, 9.3-145.8). Athletes with a lifelong exercise volume >2000
      MET-min/wk (n=75) had a significantly higher CAC score (9.4 [interquartile range,
      0-60.9] versus 0 [interquartile range, 0-43.5]; P=0.02) and prevalence of CAC
      (68%; adjusted odds ratio [ORadjusted]=3.2; 95% confidence interval [CI], 1.6
      6.6) and plaque (77%; ORadjusted=3.3; 95% CI, 1.6-7.1) compared with <1000 MET
      min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (>=9
      MET) was associated with CAC (ORadjusted=1.47; 95% CI, 1.14-1.91) and plaque
      (ORadjusted=1.56; 95% CI, 1.17-2.08). Among participants with CAC>0, there was no
      difference in CAC score (P=0.20), area (P=0.21), density (P=0.25), and regions of
      interest (P=0.20) across exercise volume groups. Among participants with plaque,
      the most active group (>2000 MET-min/wk) had a lower prevalence of mixed plaques
      (48% versus 69%; ORadjusted=0.35; 95% CI, 0.15-0.85) and more often had only
      calcified plaques (38% versus 16%; ORadjusted=3.57; 95% CI, 1.28-9.97) compared
      with the least active group (<1000 MET-min/wk). CONCLUSIONS: Participants in the
      >2000 MET-min/wk group had a higher prevalence of CAC and atherosclerotic
      plaques. The most active group, however, had a more benign composition of
      plaques, with fewer mixed plaques and more often only calcified plaques. These
      observations may explain the increased longevity typical of endurance athletes
      despite the presence of more coronary atherosclerotic plaque in the most active
      participants.

PMID- 28450348
TI  - Melanocortin 1 Receptor Signaling Regulates Cholesterol Transport in Macrophages.
AB  - BACKGROUND: The melanocortin 1 receptor (MC1-R) is expressed by monocytes and
      macrophages, where it exerts anti-inflammatory actions on stimulation with its
      natural ligand alpha-melanocyte-stimulating hormone. The present study was
      designed to investigate the specific role of MC1-R in the context of
      atherosclerosis and possible regulatory pathways of MC1-R beyond anti
      inflammation. METHODS: Human and mouse atherosclerotic samples and primary mouse
      macrophages were used to study the regulatory functions of MC1-R. The impact of
      pharmacological MC1-R activation on atherosclerosis was assessed in
      apolipoprotein E-deficient mice. RESULTS: Characterization of human and mouse
      atherosclerotic plaques revealed that MC1-R expression localizes in lesional
      macrophages and is significantly associated with the ATP-binding cassette
      transporters ABCA1 and ABCG1, which are responsible for initiating reverse
      cholesterol transport. Using bone marrow-derived macrophages, we observed that
      alpha-melanocyte-stimulating hormone and selective MC1-R agonists similarly
      promoted cholesterol efflux, which is a counterregulatory mechanism against foam
      cell formation. Mechanistically, MC1-R activation upregulated the levels of ABCA1
      and ABCG1. These effects were accompanied by a reduction in cell surface CD36
      expression and in cholesterol uptake, further protecting macrophages from
      excessive lipid accumulation. Conversely, macrophages deficient in functional MC1
      R displayed a phenotype with impaired efflux and enhanced uptake of cholesterol.
      Pharmacological targeting of MC1-R in atherosclerotic apolipoprotein E-deficient
      mice reduced plasma cholesterol levels and aortic CD36 expression and increased
      plaque ABCG1 expression and signs of plaque stability. CONCLUSIONS: Our findings
      identify a novel role for MC1-R in macrophage cholesterol transport. Activation
      of MC1-R confers protection against macrophage foam cell formation through a dual
      mechanism: It prevents cholesterol uptake while concomitantly promoting ABCA1-
      and ABCG1-mediated reverse cholesterol transport.

PMID- 28450349
TI  - Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity: Evidence
      From Mouse and Human Studies.
AB  - BACKGROUND: The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor)
      cell homeostasis and trafficking. So far, an atheroprotective role of
      CXCL12/CXCR4 has only been implied through pharmacological intervention, in
      particular, because the somatic deletion of the CXCR4 gene in mice is
      embryonically lethal. Moreover, cell-specific effects of CXCR4 in the arterial
      wall and underlying mechanisms remain elusive, prompting us to investigate the
      relevance of CXCR4 in vascular cell types for atheroprotection. METHODS: We
      examined the role of vascular CXCR4 in atherosclerosis and plaque composition by
      inducing an endothelial cell (BmxCreERT2-driven)-specific or smooth muscle cell
      (SMC, SmmhcCreERT2- or TaglnCre-driven)-specific deficiency of CXCR4 in an
      apolipoprotein E-deficient mouse model. To identify underlying mechanisms for
      effects of CXCR4, we studied endothelial permeability, intravital leukocyte
      adhesion, involvement of the Akt/WNT/beta-catenin signaling pathway and relevant
      phosphatases in VE-cadherin expression and function, vascular tone in aortic
      rings, cholesterol efflux from macrophages, and expression of SMC phenotypic
      markers. Finally, we analyzed associations of common genetic variants at the
      CXCR4 locus with the risk for coronary heart disease, along with CXCR4 transcript
      expression in human atherosclerotic plaques. RESULTS: The cell-specific deletion
      of CXCR4 in arterial endothelial cells (n=12-15) or SMCs (n=13-24) markedly
      increased atherosclerotic lesion formation in hyperlipidemic mice. Endothelial
      barrier function was promoted by CXCL12/CXCR4, which triggered Akt/WNT/beta
      catenin signaling to drive VE-cadherin expression and stabilized junctional VE
      cadherin complexes through associated phosphatases. Conversely, endothelial CXCR4
      deficiency caused arterial leakage and inflammatory leukocyte recruitment during
      atherogenesis. In arterial SMCs, CXCR4 sustained normal vascular reactivity and
      contractile responses, whereas CXCR4 deficiency favored a synthetic phenotype,
      the occurrence of macrophage-like SMCs in the lesions, and impaired cholesterol
      efflux. Regression analyses in humans (n=259 796) identified the C-allele at
      rs2322864 within the CXCR4 locus to be associated with increased risk for
      coronary heart disease. In line, C/C risk genotype carriers showed reduced CXCR4
      expression in carotid artery plaques (n=188), which was furthermore associated
      with symptomatic disease. CONCLUSIONS: Our data clearly establish that vascular
      CXCR4 limits atherosclerosis by maintaining arterial integrity, preserving
      endothelial barrier function, and a normal contractile SMC phenotype. Enhancing
      these beneficial functions of arterial CXCR4 by selective modulators might open
      novel therapeutic options in atherosclerosis.

PMID- 28450353
TI  - Meet the First Authors.

PMID- 28450350
TI  - Cholesterol Efflux Capacity, High-Density Lipoprotein Particle Number, and
      Incident Cardiovascular Events: An Analysis From the JUPITER Trial (Justification
      for the Use of Statins in Prevention: An Intervention Trial Evaluating
      Rosuvastatin).
AB  - BACKGROUND: Recent failures of drugs that raised high-density lipoprotein (HDL)
      cholesterol levels to reduce cardiovascular events in clinical trials have led to
      increased interest in alternative indices of HDL quality, such as cholesterol
      efflux capacity, and HDL quantity, such as HDL particle number. However, no
      studies have directly compared these metrics in a contemporary population that
      includes potent statin therapy and low low-density lipoprotein cholesterol.
      METHODS: HDL cholesterol levels, apolipoprotein A-I, cholesterol efflux capacity,
      and HDL particle number were assessed at baseline and 12 months in a nested case
      control study of the JUPITER trial (Justification for the Use of Statins in
      Prevention: An Intervention Trial Evaluating Rosuvastatin), a randomized primary
      prevention trial that compared rosuvastatin treatment to placebo in individuals
      with normal low-density lipoprotein cholesterol but increased C-reactive protein
      levels. In total, 314 cases of incident cardiovascular disease (CVD) (myocardial
      infarction, unstable angina, arterial revascularization, stroke, or
      cardiovascular death) were compared to age- and gender-matched controls.
      Conditional logistic regression models adjusting for risk factors evaluated
      associations between HDL-related biomarkers and incident CVD. RESULTS:
      Cholesterol efflux capacity was moderately correlated with HDL cholesterol,
      apolipoprotein A-I, and HDL particle number (Spearman r= 0.39, 0.48, and 0.39
      respectively; P<0.001). Baseline HDL particle number was inversely associated
      with incident CVD (adjusted odds ratio per SD increment [OR/SD], 0.69; 95%
      confidence interval [CI], 0.56-0.86; P<0.001), whereas no significant association
      was found for baseline cholesterol efflux capacity (OR/SD, 0.89; 95% CI, 0.72
      1.10; P=0.28), HDL cholesterol (OR/SD, 0.82; 95% CI, 0.66-1.02; P=0.08), or
      apolipoprotein A-I (OR/SD, 0.83; 95% CI, 0.67-1.03; P=0.08). Twelve months of
      rosuvastatin (20 mg/day) did not change cholesterol efflux capacity (average
      percentage change -1.5%, 95% CI, -13.3 to +10.2; P=0.80), but increased HDL
      cholesterol (+7.7%), apolipoprotein A-I (+4.3%), and HDL particle number (+5.2%).
      On-statin cholesterol efflux capacity was inversely associated with incident CVD
      (OR/SD, 0.62; 95% CI, 0.42-0.92; P=0.02), although HDL particle number again
      emerged as the strongest predictor (OR/SD, 0.51; 95% CI, 0.33-0.77; P<0.001).
      CONCLUSIONS: In JUPITER, cholesterol efflux capacity was associated with incident
      CVD in individuals on potent statin therapy but not at baseline. For both
      baseline and on-statin analyses, HDL particle number was the strongest of 4 HDL
      related biomarkers as an inverse predictor of incident events and biomarker of
      residual risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00239681.

PMID- 28450354
TI  - Deciphering Histone Code Enigmas Sheds New Light on Cardiac Regeneration.

PMID- 28450351
TI  - Prospective Study of Adenosine on Atrioventricular Nodal Conduction in Pediatric
      and Young Adult Patients After Heart Transplantation.
AB  - BACKGROUND: Supraventricular tachycardia is common after heart transplantation.
      Adenosine, the standard therapy for treating supraventricular tachycardia in
      children and adults without transplantation, is relatively contraindicated after
      transplantation because of a presumed risk of prolonged atrioventricular block in
      denervated hearts. This study tested whether adenosine caused prolonged asystole
      after transplantation and if it was effective in blocking atrioventricular nodal
      conduction in these patients. METHODS: This was a single-center prospective
      clinical study including healthy heart transplant recipients 6 months to 25 years
      of age presenting for routine cardiac catheterization during 2015 to 2016. After
      catheterization, a transvenous pacing catheter was placed and adenosine was given
      following a dose-escalation protocol until atrioventricular block was achieved.
      The incidence of clinically significant asystole (>=12 seconds after adenosine)
      was quantified. The effects of patient characteristics on adenosine dose required
      to produce atrioventricular block and duration of effect were also measured.
      RESULTS: Eighty patients completed adenosine testing. No patient (0%; 95%
      confidence interval, 0-3) required rescue ventricular pacing. Atrioventricular
      block was observed in 77 patients (96%; 95% confidence interval, 89-99). The
      median longest atrioventricular block was 1.9 seconds (interquartile range, 1.4
      3.2 seconds), with a mean duration of adenosine effect of 4.3+/-2.0 seconds. No
      patient characteristic significantly predicted the adenosine dose to produce
      atrioventricular block or duration of effect. Results were similar across patient
      weight categories. CONCLUSIONS: Adenosine induces atrioventricular block in
      healthy pediatric and young adult heart transplant recipients with minimal risk
      when low initial doses are used (25 MUg/kg; 1.5 mg if >=60 kg) and therapy is
      gradually escalated. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT02462941.

PMID- 28450355
TI  - ORAI1 Controls the Unique Adjustment of Lymphatics to Fluid Flow.

PMID- 28450356
TI  - How to Cross the Lymphatic Fence: Lessons From Solute Transport.

PMID- 28450357
TI  - Regenerative Angiogenesis: Quality Over Quantity.

PMID- 28450358
TI  - Long Live Partial Reprogramming.

PMID- 28450359
TI  - Danny El-Nachef: Worldly Perspectives for the Heart.

PMID- 28450360
TI  - The Max Planck Institute for Heart and Lung Research Curiosity-Driven Basic
      Research to Fight Cardio-Pulmonary Diseases.

PMID- 28450361
TI  - Treat the Patient, Not Just the Cell!

PMID- 28450362
TI  - Changing Direction: From Therapeutic Telomerase Inhibition to Activation?

PMID- 28450363
TI  - Controversies About Atrial Fibrillation Mechanisms: Aiming for Order in Chaos and
      Whether it Matters.

PMID- 28450364
TI  - The Emerging Role of miR-200 Family in Cardiovascular Diseases.

PMID- 28450365
TI  - Critical Issues for the Translation of Cardioprotection.
AB  - The translation from numerous successful animal experiments on cardioprotection
      beyond that by reperfusion to clinical practice has to date been disappointing.
      Animal experiments often use reductionist approaches and are mostly performed in
      young and healthy animals which lack the risk factors, comorbidities, and
      comedications which are characteristics of patients suffering an acute myocardial
      infarction or undergoing cardiovascular surgery. Conceptually, it is still
      unclear by how much the time window for successful reperfusion is extended by
      preconditioning, and how long the duration of ischemia can be so that adjunct
      cardioprotection by postconditioning at reperfusion still protects. Experimental
      studies addressing long-term effects of adjunct cardioprotection beyond infarct
      size reduction, that is, on repair, remodeling, and mortality, are lacking.
      Technically, reproducibility and robustness of experimental studies are often
      limited. Grave faults in design and conduct of clinical trials have also
      substantially contributed to the failure of translation of cardioprotection to
      clinical practice. Cardiovascular surgery with ischemic cardioplegic arrest is
      only a surrogate of acute myocardial infarction and confounded by the choice of
      anesthesia, hypothermia, cardioplegia, and traumatic myocardial injury. Trials in
      patients with acute myocardial infarction have been performed on
      agents/interventions with no or inconsistent previous animal data and in patients
      who had either some reperfusion already at admission or were reperfused too late
      to expect any myocardial salvage. Of greatest concern is the lack of adequate
      phase II dosing and timing studies when rushing from promising proof-of-concept
      trials with surrogate end points such as infarct size to larger clinical outcome
      trials. Future trials must focus on interventions/agents with robust preclinical
      evidence, have solid phase II dosing and timing data, and recruit patients who
      have truly a chance to benefit from adjunct cardioprotection.

PMID- 28450366
TI  - Engineering Cardiac Muscle Tissue: A Maturating Field of Research.
AB  - Twenty years after the initial description of a tissue engineered construct, 3
      dimensional human cardiac tissues of different kinds are now generated routinely
      in many laboratories. Advances in stem cell biology and engineering allow for the
      generation of constructs that come close to recapitulating the complex structure
      of heart muscle and might, therefore, be amenable to industrial (eg, drug
      screening) and clinical (eg, cardiac repair) applications. Whether the more
      physiological structure of 3-dimensional constructs provides a relevant advantage
      over standard 2-dimensional cell culture has yet to be shown in head-to-head
      comparisons. The present article gives an overview on current strategies of
      cardiac tissue engineering with a focus on different hydrogel methods and
      discusses perspectives and challenges for necessary steps toward the real-life
      application of cardiac tissue engineering for disease modeling, drug development,
      and cardiac repair.

PMID- 28450368
TI  - Plasma Glycated CD59, a Novel Biomarker for Detection of Pregnancy-Induced
      Glucose Intolerance.
AB  - OBJECTIVE: Plasma glycated CD59 (pGCD59) is an emerging biomarker in diabetes. We
      assessed whether pGCD59 could predict the following: the results of the glucose
      challenge test (GCT) for screening of gestational diabetes mellitus (GDM)
      (primary analysis); and the diagnosis of GDM and prevalence of large for
      gestational age (LGA) newborns (secondary analyses). RESEARCH DESIGN AND METHODS:
      Case-control study of 1,000 plasma samples from women receiving standard prenatal
      care, 500 women having a normal GCT (control subjects) and 500 women with a
      failed GCT and a subsequent oral glucose tolerance test (case patients). RESULTS:
      Compared with control subjects, the median (interquartile range) pGCD59 value was
      8.5-fold higher in case patients and 10-fold higher in GDM patients, as follows:
      control subjects 0.33 (0.19); case patients 2.79 (1.4); GDM patients 3.23 (1.43)
      (P < 0.001); area under the receiver operating characteristic curve 0.92. LGA
      prevalence was 4.3% in the lowest quartile and 13.5% in the highest quartile of
      pGCD59. CONCLUSIONS: One pGCD59 measurement during weeks 24-28 identifies
      pregnancy-induced glucose intolerance with high sensitivity and specificity and
      can potentially identify the risk for LGA.

PMID- 28450367
TI  - Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes.
AB  - The past 3 decades have been characterized by an exponential growth in knowledge
      and advances in the clinical treatment of atrial fibrillation (AF). It is now
      known that AF genesis requires a vulnerable atrial substrate and that the
      formation and composition of this substrate may vary depending on comorbid
      conditions, genetics, sex, and other factors. Population-based studies have
      identified numerous factors that modify the atrial substrate and increase AF
      susceptibility. To date, genetic studies have reported 17 independent signals for
      AF at 14 genomic regions. Studies have established that advanced age, male sex,
      and European ancestry are prominent AF risk factors. Other modifiable risk
      factors include sedentary lifestyle, smoking, obesity, diabetes mellitus,
      obstructive sleep apnea, and elevated blood pressure predispose to AF, and each
      factor has been shown to induce structural and electric remodeling of the atria.
      Both heart failure and myocardial infarction increase risk of AF and vice versa
      creating a feed-forward loop that increases mortality. Other cardiovascular
      outcomes attributed to AF, including stroke and thromboembolism, are well
      established, and epidemiology studies have championed therapeutics that mitigate
      these adverse outcomes. However, the role of anticoagulation for preventing
      dementia attributed to AF is less established. Our review is a comprehensive
      examination of the epidemiological data associating unmodifiable and modifiable
      risk factors for AF and of the pathophysiological evidence supporting the
      mechanistic link between each risk factor and AF genesis. Our review also
      critically examines the epidemiological data on clinical outcomes attributed to
      AF and summarizes current evidence linking each outcome with AF.

PMID- 28450369
TI  - A Chromosome-Scale Assembly of the Bactrocera cucurbitae Genome Provides Insight
      to the Genetic Basis of white pupae.
AB  - Genetic sexing strains (GSS) used in sterile insect technique (SIT) programs are
      textbook examples of how classical Mendelian genetics can be directly implemented
      in the management of agricultural insect pests. Although the foundation of
      traditionally developed GSS are single locus, autosomal recessive traits, their
      genetic basis are largely unknown. With the advent of modern genomic techniques,
      the genetic basis of sexing traits in GSS can now be further investigated. This
      study is the first of its kind to integrate traditional genetic techniques with
      emerging genomics to characterize a GSS using the tephritid fruit fly pest
      Bactrocera cucurbitae as a model. These techniques include whole-genome
      sequencing, the development of a mapping population and linkage map, and
      quantitative trait analysis. The experiment designed to map the genetic sexing
      trait in B. cucurbitae, white pupae (wp), also enabled the generation of a
      chromosome-scale genome assembly by integrating the linkage map with the
      assembly. Quantitative trait loci analysis revealed SNP loci near position 42 MB
      on chromosome 3 to be tightly linked to wp Gene annotation and synteny analysis
      show a near perfect relationship between chromosomes in B. cucurbitae and Muller
      elements A-E in Drosophila melanogaster This chromosome-scale genome assembly is
      complete, has high contiguity, was generated using a minimal input DNA, and will
      be used to further characterize the genetic mechanisms underlying wp Knowledge of
      the genetic basis of genetic sexing traits can be used to improve SIT in this
      species and expand it to other economically important Diptera.

PMID- 28450370
TI  - Comparative Genomics of the Ectomycorrhizal Sister Species Rhizopogon vinicolor
      and Rhizopogon vesiculosus (Basidiomycota: Boletales) Reveals a Divergence of the
      Mating Type B Locus.
AB  - Divergence of breeding system plays an important role in fungal speciation.
      Ectomycorrhizal fungi, however, pose a challenge for the study of reproductive
      biology because most cannot be mated under laboratory conditions. To overcome
      this barrier, we sequenced the draft genomes of the ectomycorrhizal sister
      species Rhizopogon vinicolor Smith and Zeller and R. vesiculosus Smith and Zeller
      (Basidiomycota, Boletales)-the first genomes available for Basidiomycota truffles
      and characterized gene content and organization surrounding their mating type
      loci. Both species possess a pair of homeodomain transcription factor homologs at
      the mating type A-locus as well as pheromone receptor and pheromone precursor
      homologs at the mating type B-locus. Comparison of Rhizopogon genomes with
      genomes from Boletales, Agaricales, and Polyporales revealed synteny of the A
      locus region within Boletales, but several genomic rearrangements across orders.
      Our findings suggest correlation between gene content at the B-locus region and
      breeding system in Boletales with tetrapolar species possessing more diverse gene
      content than bipolar species. Rhizopogon vinicolor possesses a greater number of
      B-locus pheromone receptor and precursor genes than R. vesiculosus, as well as a
      pair of isoprenyl cysteine methyltransferase genes flanking the B-locus compared
      to a single copy in R. vesiculosus Examination of dikaryotic single nucleotide
      polymorphisms within genomes revealed greater heterozygosity in R. vinicolor,
      consistent with increased rates of outcrossing. Both species possess the
      components of a heterothallic breeding system with R. vinicolor possessing a B
      locus region structure consistent with tetrapolar Boletales and R. vesiculosus
      possessing a B-locus region structure intermediate between bipolar and tetrapolar
      Boletales.

PMID- 28450371
TI  - Adaptive Roles of SSY1 and SIR3 During Cycles of Growth and Starvation in
      Saccharomyces cerevisiae Populations Enriched for Quiescent or Nonquiescent
      Cells.
AB  - Over its evolutionary history, Saccharomyces cerevisiae has evolved to be well
      adapted to fluctuating nutrient availability. In the presence of sufficient
      nutrients, yeast cells continue to proliferate, but upon starvation haploid yeast
      cells enter stationary phase and differentiate into nonquiescent (NQ) and
      quiescent (Q) cells. Q cells survive stress better than NQ cells and show greater
      viability when nutrient-rich conditions are restored. To investigate the genes
      that may be involved in the differentiation of Q and NQ cells, we serially
      propagated yeast populations that were enriched for either only Q or only NQ cell
      types over many repeated growth-starvation cycles. After 30 cycles (equivalent to
      300 generations), each enriched population produced a higher proportion of the
      enriched cell type compared to the starting population, suggestive of adaptive
      change. We also observed differences in each population's fitness suggesting
      possible tradeoffs: clones from NQ lines were better adapted to logarithmic
      growth, while clones from Q lines were better adapted to starvation. Whole-genome
      sequencing of clones from Q- and NQ-enriched lines revealed mutations in genes
      involved in the stress response and survival in limiting nutrients (ECM21, RSP5,
      MSN1, SIR4, and IRA2) in both Q and NQ lines, but also differences between the
      two lines: NQ line clones had recurrent independent mutations affecting the Ssy1p
      Ptr3p-Ssy5p (SPS) amino acid sensing pathway, while Q line clones had recurrent,
      independent mutations in SIR3 and FAS1 Our results suggest that both sets of
      enriched-cell type lines responded to common, as well as distinct, selective
      pressures.

PMID- 28450372
TI  - Evolutionary Conservation and Emerging Functional Diversity of the Cytosolic
      Hsp70:J Protein Chaperone Network of Arabidopsis thaliana.
AB  - Heat shock proteins of 70 kDa (Hsp70s) partner with structurally diverse Hsp40s
      (J proteins), generating distinct chaperone networks in various cellular
      compartments that perform myriad housekeeping and stress-associated functions in
      all organisms. Plants, being sessile, need to constantly maintain their cellular
      proteostasis in response to external environmental cues. In these situations, the
      Hsp70:J protein machines may play an important role in fine-tuning cellular
      protein quality control. Although ubiquitous, the functional specificity and
      complexity of the plant Hsp70:J protein network has not been studied. Here, we
      analyzed the J protein network in the cytosol of Arabidopsis thaliana and, using
      yeast genetics, show that the functional specificities of most plant J proteins
      in fundamental chaperone functions are conserved across long evolutionary
      timescales. Detailed phylogenetic and functional analysis revealed that increased
      number, regulatory differences, and neofunctionalization in J proteins together
      contribute to the emerging functional diversity and complexity in the Hsp70:J
      protein network in higher plants. Based on the data presented, we propose that
      higher plants have orchestrated their "chaperome," especially their J protein
      complement, according to their specialized cellular and physiological
      stipulations.

PMID- 28450373
TI  - RNAseq Analysis of the Drosophila Response to the Entomopathogenic Nematode
      Steinernema.
AB  - Drosophila melanogaster is an outstanding model to study the molecular and
      functional basis of host-pathogen interactions. Currently, our knowledge of
      microbial infections in D. melanogaster is well understood; however, the response
      of flies to nematode infections is still in its infancy. Here, we have used the
      potent parasitic nematode Steinernema carpocapsae, which lives in mutualism with
      its endosymbiotic bacteria Xenorhabdus nematophila, to examine the transcriptomic
      basis of the interaction between D. melanogaster and entomopathogenic nematodes.
      We have employed next-generation RNA sequencing (RNAseq) to investigate the
      transcriptomic profile of D. melanogaster larvae in response to infection by S.
      carpocapsae symbiotic (carrying X. nematophila) or axenic (lacking X.
      nematophila) nematodes. Bioinformatic analyses have identified the strong
      induction of genes that are associated with the peritrophic membrane and the
      stress response, as well as several genes that participate in developmental
      processes. We have also found that genes with different biological functions are
      enriched in D. melanogaster larvae responding to either symbiotic or axenic
      nematodes. We further show that while symbiotic nematode infection enriched
      certain known immune-related genes, axenic nematode infection enriched several
      genes associated with chitin binding, lipid metabolic functions, and neuroactive
      ligand receptors. In addition, we have identified genes with a potential role in
      nematode recognition and genes with potential antinematode activity. Findings
      from this study will undoubtedly set the stage for the identification of key
      regulators of antinematode immune mechanisms in D. melanogaster, as well as in
      other insects of socioeconomic importance.

PMID- 28450374
TI  - Genetic Architecture of a Rice Nested Association Mapping Population.
AB  - Describing the genetic diversity in the gene pool of crops will provide breeders
      with novel resources for varietal improvement. Nested Association Mapping (NAM)
      populations are uniquely suited for characterizing parental diversity through the
      shuffling and fixation of parental haplotypes. Here, we describe a set of 1879
      rice NAM lines created through the selfing and single-seed descent of F1 hybrids
      derived from elite IR64 indica crossed with 10 diverse tropical japonica lines.
      Genotyping data indicated tropical japonica alleles were captured at every
      queried locus despite the presence of segregation distortion factors. Several
      distortion loci were mapped, both shared and unique, among the 10 populations.
      Using two-point and multi-point genetic map calculations, our datasets achieved
      the ~1500 cM expected map size in rice. Finally, we highlighted the utility of
      the NAM lines for QTL mapping, including joint analysis across the 10
      populations, by confirming known QTL locations for the trait days to heading.

PMID- 28450375
TI  - BiFCROS: A Low-Background Fluorescence Repressor Operator System for Labeling of
      Genomic Loci.
AB  - Fluorescence-based methods are widely used to analyze elementary cell processes
      such as DNA replication or chromosomal folding and segregation. Labeling DNA with
      a fluorescent protein allows the visualization of its temporal and spatial
      organization. One popular approach is FROS (fluorescence repressor operator
      system). This method specifically labels DNA in vivo through binding of a fusion
      of a fluorescent protein and a repressor protein to an operator array, which
      contains numerous copies of the repressor binding site integrated into the
      genomic site of interest. Bound fluorescent proteins are then visible as foci in
      microscopic analyses and can be distinguished from the background fluorescence
      caused by unbound fusion proteins. Even though this method is widely used, no
      attempt has been made so far to decrease the background fluorescence to
      facilitate analysis of the actual signal of interest. Here, we present a new
      method that greatly reduces the background signal of FROS. BiFCROS (Bimolecular
      Fluorescence Complementation and Repressor Operator System) is based on fusions
      of repressor proteins to halves of a split fluorescent protein. Binding to a
      hybrid FROS array results in fluorescence signals due to bimolecular fluorescence
      complementation. Only proteins bound to the hybrid FROS array fluoresce, greatly
      improving the signal to noise ratio compared to conventional FROS. We present the
      development of BiFCROS and discuss its potential to be used as a fast and single
      cell readout for copy numbers of genetic loci.

PMID- 28450376
TI  - Genome-Wide Exome Analysis of Cmv5-Disparate Mouse Strains that Differ in Host
      Resistance to Murine Cytomegalovirus Infection.
AB  - Host resistance to murine cytomegalovirus (MCMV) varies in different strains of
      laboratory mice due to differences in expression of determinants that control and
      clear viral infection. The major histocompatibility complex class I Dk molecule
      is one such determinant that controls MCMV through the action of natural killer
      (NK) cells. However, the extent of NK cell-mediated Dk-dependent resistance to
      infection varies in different mouse strains. The molecular genetic basis of this
      variation remains unclear. Previous work to examine the Dk effect on MCMV
      resistance in MA/My * C57L offspring discovered multiple quantitative trait loci
      (QTL) that may serve to modify NK cells or their capacity to respond during MCMV
      infection. One QTL in particular, Cmv5, was found to regulate the frequency of NK
      cells and secondary lymphoid organ structure in spleen during MCMV infection.
      Cmv5 alleles, however, have not been identified. We therefore sequenced and
      analyzed genome-wide exome (GWE) variants, including those aligned to the
      critical genetic interval, in Cmv5-disparate mouse strains. Their GWE variant
      profiles were compared to assess strain-specific sequence data integrity and to
      analyze mouse strain relatedness across the genome. GWE content was further
      compared against data from the Mouse Genomes Project. This approach was developed
      as a platform for using GWE variants to define genomic regions of divergence and
      similarity in different mouse strains while also validating the overall quality
      of GWE sequence data. Moreover, the analysis provides a framework for the
      selection of novel QTL candidate sequences, including at the Cmv5 critical
      region.

PMID- 28450377
TI  - Fundus findings in a series of patients with extrapulmonary tuberculosis in
      Thailand.
AB  - AIM: The aim of this study was to determine the frequency of fundus abnormalities
      among patients who are undergoing or have recently completed treatment for
      extrapulmonary tuberculosis (eTB). METHODS: This is a prospective cross-sectional
      study conducted in a TB clinic of a tertiary hospital in northern Thailand. All
      patients who had eTB between January 2014 and August 2015 were invited by
      telephone to return to the clinic for fundus photography. Three uveitis
      specialists reviewed all photographs to identify posterior segment lesions that
      were consistent with ocular TB. RESULTS: A total of 265 patients were diagnosed
      with eTB during the specified period, of which 118 (44.5%) were reached by
      telephone and 60 (50.8%) participated in the study. A total of 7 eyes from six
      patients (10.0% of participants, 95% CI 2.2% to 17.8%) had lesions consistent
      with ocular TB. The group with possible ocular TB lesions was on average 16.8
      years older than those without ocular lesions (p=0.01), but the two groups were
      otherwise not significantly different. CONCLUSION: Ocular lesions consistent with
      TB were not rare in a group of patients who were undergoing or had recently
      completed treatment for eTB. Fundus examination may provide diagnostic
      information that could influence a clinician's beliefs when diagnosing eTB. Given
      the low costs and immediate results of eye examination, this diagnostic test
      should be considered in patients suspected for eTB, especially when other tests
      are negative.

PMID- 28450378
TI  - Long-term outcomes of orbital fat decompression in Graves' orbitopathy.
AB  - PURPOSE: To evaluate the long-term clinical efficacy of orbital fat decompression
      in treating proptosis in Graves' ophthalmopathy (GO). METHODS: Retrospective
      review of 1604 eyes of 845 patients with symmetric (1518 eyes) and asymmetric (86
      eyes) proptosis who received orbital fat decompression between 2003 and 2014.
      Changes in Hertel values were evaluated at baseline, 6 months postoperatively and
      yearly thereafter. Recurrence of proptosis, diplopia and other complications that
      required additional surgeries were documented and analysed. The surgical outcome
      was defined as complete success if there was proptosis reduction with no
      recurrence and improved or no diplopia. Partial success was considered if there
      was proptosis reduction without recurrence yet persistent or new-onset diplopia.
      Failure was considered if there was recurrence of proptosis regardless of
      diplopia. The patient's quality of life was also evaluated as a long-term
      outcome. RESULTS: After follow-up for 37.9+/-24.4 months, 1365 eyes (85.1%)
      achieved complete success, 219 eyes (13.7%) achieved partial success and 20 eyes
      (1.2%) had failure. Newly onset diplopia and secondary decompression occurrence
      rate remained low at 3.3% and 0.6%, respectively. The total proptosis reduction
      was 4.1+/-1.3 mm, which was consistent all through the intermediate and long-term
      (5-10 years) follow-up. The amount of orbital fat removal (4.5+/-1.1 mL) played a
      significant role in the long-term Hertel change. Importantly, the overall quality
      of life increased significantly for GO patients after undergoing orbital fat
      decompression. CONCLUSIONS: Orbital fat decompression has a long-term efficacy in
      correcting disfiguring proptosis with a low complication rate and without the
      need of secondary decompression procedures. This was also associated with a
      significant improvement in quality of life.

PMID- 28450379
TI  - Posner-Schlossman syndrome in Wenzhou, China: a retrospective review study.
AB  - AIM: To describe the incidence of Posner-Schlossman syndrome (PSS) in Lucheng
      District, Wenzhou, China, over a 10-year period. METHODS: We reviewed
      retrospectively the medical records of all inpatient and outpatient patients
      diagnosed with PSS during the years 2005-2014 in the Eye Hospital of Wenzhou
      Medical University. The keywords of 'glaucomatocyclitic crisis', 'Posner
      Schlossman syndrome' and 'PSS' were used for the retrieval. Only patients with
      registered residing address in Lucheng District where the hospital located were
      finally selected. The cumulative incidence and annual incidence of PSS were
      calculated based on the sum of household registered population and temporary
      resident population in Lucheng District. RESULTS: A total of 576 patients with
      PSS (339 men and 237 women) met the retrieval criteria. The mean age of these
      subjects at the first clinic visit was 40+/-15 years. Intraocular pressure (IOP)
      of the initial record was 31.91+/-15.37 mm Hg. The 10-year cumulative incidence
      of PSS in Lucheng District was 39.53 per 100 000 population, whereas the mean
      annual incidence of PSS in this area was 3.91 per 100 000 population. The
      majority of these patients were aged 20-59 years (83.9%). Men showed a
      significantly higher cumulative incidence of PSS than women (p=0.010). Higher
      rate of newly onset cases was found in spring (31%) than in other seasons
      (p=0.006). CONCLUSIONS: Our results suggest a relatively high incidence of PSS in
      Wenzhou, a southeastern city in China. Young, male adults are prone to be
      affected in spring. However, the aetiology and other risk factors are still
      waited to be clarified.

PMID- 28450380
TI  - In vivo confocal microscopy and tear cytokine analysis in post-LASIK ectasia.
AB  - AIM: Corneal keratectasia is one of the complications associated with laser in
      situ keratomileusis (LASIK) that results in vision impairment. The pathogenesis
      of post-LASIK ectasia (PLE) remains underexplored. We report the tear cytokine
      profile and in vivo confocal microscopy (IVCM) findings in eyes with PLE.
      METHODS: This retrospective study included age-matched 7 (14 eyes) post-LASIK
      controls (PLCs) and 6 (12 eyes) PLE subjects. Corneal topography was used to
      categorise the subjects into PLC and PLE groups. Ocular Surface Disease Index
      (OSDI) scores obtained were based on standard questionnaire and IVCM images were
      used to determine corneal dendritic cells density (DCD) and sub-basal nerve
      plexus morphology. Inflammatory cytokines/chemokines in the tears were quantified
      using flow cytometry based cytometric bead array. RESULTS: Pentacam-based scores,
      OSDI scores and corneal DCD were significantly (p<0.05) higher in patients with
      PLE compared with PLC. Discomfort-related subscale of OSDI score exhibited a
      positive correlation with total corneal DCD in the PLE cohort. The fold
      difference of chemokine (C-C motif) ligand/monocyte chemotactic protein-1
      (CCL2/MCP1) (3.4+/-0.6) was found to be significantly (p<0.05) higher in the PLE
      cohorts and a positive correlation between CCL2/MCP1 levels and total corneal DCD
      was also observed in the PLE cohort. CONCLUSION: The current study found a
      significant difference in the tear film cytokine profile between normal and PLE
      eyes. Presence of increased corneal dendritic cells and altered tear cytokines
      suggests an ongoing inflammatory response in PLE.

PMID- 28450381
TI  - Investigating the usefulness of a cluster-based trend analysis to detect visual
      field progression in patients with open-angle glaucoma.
AB  - BACKGROUND/AIMS: To investigate the usefulness of the Octopus (Haag-Streit)
      EyeSuite's cluster trend analysis in glaucoma. METHODS: Ten visual fields (VFs)
      with the Humphrey Field Analyzer (Carl Zeiss Meditec), spanning 7.7 years on
      average were obtained from 728 eyes of 475 primary open angle glaucoma patients.
      Mean total deviation (mTD) trend analysis and EyeSuite's cluster trend analysis
      were performed on various series of VFs (from 1st to 10th: VF1-10 to 6th to 10th:
      VF6-10). The results of the cluster-based trend analysis, based on different
      lengths of VF series, were compared against mTD trend analysis. RESULT: Cluster
      based trend analysis and mTD trend analysis results were significantly associated
      in all clusters and with all lengths of VF series. Between 21.2% and 45.9%
      (depending on VF series length and location) of clusters were deemed to progress
      when the mTD trend analysis suggested no progression. On the other hand, 4.8% of
      eyes were observed to progress using the mTD trend analysis when cluster trend
      analysis suggested no progression in any two (or more) clusters. CONCLUSION:
      Whole field trend analysis can miss local VF progression. Cluster trend analysis
      appears as robust as mTD trend analysis and useful to assess both sectorial and
      whole field progression. Cluster-based trend analyses, in particular the
      definition of two or more progressing cluster, may help clinicians to detect
      glaucomatous progression in a timelier manner than using a whole field trend
      analysis, without significantly compromising specificity.

PMID- 28450383
TI  - The complex effects of ocean acidification on the prominent N2-fixing
      cyanobacterium Trichodesmium.
AB  - Acidification of seawater caused by anthropogenic carbon dioxide (CO2) is
      anticipated to influence the growth of dinitrogen (N2)-fixing phytoplankton,
      which contribute a large fraction of primary production in the tropical and
      subtropical ocean. We found that growth and N2-fixation of the ubiquitous
      cyanobacterium Trichodesmium decreased under acidified conditions,
      notwithstanding a beneficial effect of high CO2 Acidification resulted in low
      cytosolic pH and reduced N2-fixation rates despite elevated nitrogenase
      concentrations. Low cytosolic pH required increased proton pumping across the
      thylakoid membrane and elevated adenosine triphosphate production. These
      requirements were not satisfied under field or experimental iron-limiting
      conditions, which greatly amplified the negative effect of acidification.

PMID- 28450382
TI  - An adaptive signaling network in melanoma inflammatory niches confers tolerance
      to MAPK signaling inhibition.
AB  - Mitogen-activated protein kinase (MAPK) pathway antagonists induce profound
      clinical responses in advanced cutaneous melanoma, but complete remissions are
      frustrated by the development of acquired resistance. Before resistance emerges,
      adaptive responses establish a mutation-independent drug tolerance. Antagonizing
      these adaptive responses could improve drug effects, thereby thwarting the
      emergence of acquired resistance. In this study, we reveal that inflammatory
      niches consisting of tumor-associated macrophages and fibroblasts contribute to
      treatment tolerance through a cytokine-signaling network that involves macrophage
      derived IL-1beta and fibroblast-derived CXCR2 ligands. Fibroblasts require IL
      1beta to produce CXCR2 ligands, and loss of host IL-1R signaling in vivo reduces
      melanoma growth. In tumors from patients on treatment, signaling from
      inflammatory niches is amplified in the presence of MAPK inhibitors. Signaling
      from inflammatory niches counteracts combined BRAF/MEK (MAPK/extracellular signal
      regulated kinase kinase) inhibitor treatment, and consequently, inhibiting IL-1R
      or CXCR2 signaling in vivo enhanced the efficacy of MAPK inhibitors. We conclude
      that melanoma inflammatory niches adapt to and confer drug tolerance toward BRAF
      and MEK inhibitors early during treatment.

PMID- 28450384
TI  - Neandertal and Denisovan DNA from Pleistocene sediments.
AB  - Although a rich record of Pleistocene human-associated archaeological assemblages
      exists, the scarcity of hominin fossils often impedes the understanding of which
      hominins occupied a site. Using targeted enrichment of mitochondrial DNA, we show
      that cave sediments represent a rich source of ancient mammalian DNA that often
      includes traces of hominin DNA, even at sites and in layers where no hominin
      remains have been discovered. By automation-assisted screening of numerous
      sediment samples, we detected Neandertal DNA in eight archaeological layers from
      four caves in Eurasia. In Denisova Cave, we retrieved Denisovan DNA in a Middle
      Pleistocene layer near the bottom of the stratigraphy. Our work opens the
      possibility of detecting the presence of hominin groups at sites and in areas
      where no skeletal remains are found.

PMID- 28450385
TI  - Mass Spectrometry but Not Fluorimetry Distinguishes Affected and Pseudodeficiency
      Patients in Newborn Screening for Pompe Disease.
AB  - BACKGROUND: Deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA)
      causes Pompe disease. Newborn screening for Pompe disease is ongoing, and
      improved methods for distinguishing affected patients from those with
      pseudodeficiency, especially in the Asian population, would substantially reduce
      the number of patient referrals for clinical follow-up. METHODS: We measured the
      enzymatic activity of GAA in dried blood spots on newborn screening cards (DBS)
      using a tandem mass spectrometry (MS/MS) assay. The assay displayed a relatively
      large analytical range compared to the fluorimetric assay with 4
      methylumbelliferyl-alpha-glucoside. DBS from newborns confirmed to have infantile
      onset Pompe disease (IOPD, n = 11) or late-onset Pompe disease (LOPD) (n = 12)
      and those from patients bearing pseudodeficiency alleles with or without Pompe
      mutations, or Pompe disease carriers (n = 230) were studied. RESULTS: With use of
      the MS/MS GAA assay in DBS, 96% of the pseudodeficiency newborns and all of the
      Pompe disease carriers were well separated from the IOPD and LOPD newborns. The
      fluorimetric assay separated <10% of the pseudodeficiencies from the IOPD/LOPD
      group. CONCLUSIONS: The relatively large analytical range MS/MS GAA assay but not
      the fluorimetric assay in DBS provides a robust approach to reduce the number of
      referrals and should dramatically facilitate newborn screening of Pompe disease.

PMID- 28450386
TI  - Update on congenital heart disease and sudden infant/perinatal death: from
      history to future trends.
AB  - During the 20th century, expert pathologists contributed an in-depth
      characterisation of the anatomical pathology and associated pathophysiology of
      congenital heart disease (CHD). Starting in the 1970s, the reported CHD birth
      prevalence has been increasing, owing to advances in diagnostic methods. Over the
      years, surgical treatments have been associated with an enormous reduction of CHD
      mortality. Advances also have been made in understanding the developmental
      biology and molecular pathogenesis of CHD. In developed countries, sudden infant
      death syndrome (SIDS) is the most frequent form of death during the first year of
      life, with a death rate of 0.42 every 1000 births. Unexpected stillbirth has a
      six- to eightfold greater incidence than that of SIDS and remains unexplained in
      40-80% of cases even after autopsy. Specific environmental risk factors, such as
      maternal smoking, air and water pollution, food contamination, pesticides, etc,
      can interact with the genetic constitution in complex ways, which may lead to
      polymorphisms and/or mutations of specific genes, such as polymorphisms in the
      serotonin transporter gene 5-HTT, the regulator of the synaptic serotonin
      concentration. Current directions of research in this area are reviewed.

PMID- 28450387
TI  - Composite biomarker panel for prediction of severity and diagnosis of acute GVHD
      with T-cell-depleted allogeneic stem cell transplants-single centre pilot study.
AB  - AIMS: Acute graft-versus-host disease (aGVHD) is a leading cause of morbidity and
      mortality following allogeneic haematopoietic stem cell transplantation (HSCT).
      The aim of this study was to evaluate the clinical utility of a composite
      biomarker panel to help identify individuals at risk of developing aGVHD, and to
      help predict and differentiate between severity of aGVHD following T-cell
      depleted allogeneic HSCT. METHODS: We retrospectively analysed our cohort of
      biopsy confirmed patients with aGVHD, who underwent T-cell-depleted HSCT and
      matched them with negative controls without any evidence of aGVHD. Post
      transplant serum samples on days 0 and 7 and at onset of aGVHD were analysed for
      elafin, regenerating islet-derived 3-alpha, soluble tumour necrosis factor
      receptor-1, soluble interleukin-2 receptor-alpha and hepatocyte growth factor.
      Biomarker data were combined as composite panels A-F (table 2) using logistic
      regression analysis. Receiver operating characteristic analysis was performed to
      study sensitivity and specificity of the composite panels. RESULTS: Our composite
      biomarker panels significantly differentiated between aGVHD and no GVHD patients
      at time of onset (panel E) and reliably predicted severity of GVHD grades at days
      0 and 7 post-transplant (panels B and D). The area under the curve for the
      composite panel at time of onset was 0.65 with specificity, sensitivity, positive
      and negative predictive values of 100%, 55.6%, 100% and 78.9%, respectively
      (p=0.03). CONCLUSIONS: This pilot data support the usefulness of these composite
      biomarker panels in the prediction of severity and diagnosis of aGVHD in patients
      undergoing T-cell-depleted reduced intensity allogeneic HSCT.

PMID- 28450388
TI  - Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant
      assay: post hoc analysis of the TAXIT trial.
AB  - OBJECTIVE: To evaluate the clinical relevance of antidrug antibodies (ADAs)
      measured using a drug-tolerant assay in a post hoc analysis of the Trough
      Concentration (TC) Adapted Infliximab Treatment (TAXIT) randomised controlled
      trial. DESIGN: ADA in serum samples (n=221) of 76 patients enrolled in TAXIT, who
      presented with an infliximab TC <3 ug/mL at screening, were reanalysed after
      optimisation and at the end of the study using a drug-tolerant ADA assay.
      Patients underwent dose escalation to achieve therapeutic TCs between 3 ug/mL and
      7 ug/mL prior to randomisation. Patients were grouped into quartiles (Q1-4)
      according to ADA concentration at screening. RESULTS: Using a drug-tolerant
      assay, the immunogenicity detection rate increased from 21% (drug-sensitive
      assay) to 63% at screening, from 0% to 51% after optimisation and from 3% to 42%
      at the end of TAXIT. Patients in ADA Q4 required a higher cumulative infliximab
      dose (2390 (880-2998) mg) to achieve target TCs, resulting in a higher drug cost
      (?10 712 (4120-13 596)) compared with ADA-negative patients (?2060 (1648-3296))
      and patients in ADA Q1/Q2 (?2060 (1648-4120)/?2060 (1751-3296), p<0.001).
      However, all but one patient belonging to ADA Q4 were also ADA-positive using a
      drug-sensitive assay. CONCLUSIONS: Upon dose intensification, low concentration
      ADAs, not detectable using a drug-sensitive assay, disappear in more than half of
      the patients over time and are clinically non-relevant. In contrast, high
      concentration ADAs which are typically also detected in a drug-sensitive assay,
      persist over time and necessitate a higher cumulative dose and drug cost. In the
      latter group, proactive drug switching may be more cost-efficient. CLINICAL
      TRIALS REGISTER: 2011-002061-38; Post-results.

PMID- 28450389
TI  - MerTK expressing hepatic macrophages promote the resolution of inflammation in
      acute liver failure.
AB  - OBJECTIVE: Acute liver failure (ALF) is characterised by overwhelming hepatocyte
      death and liver inflammation with massive infiltration of myeloid cells in
      necrotic areas. The mechanisms underlying resolution of acute hepatic
      inflammation are largely unknown. Here, we aimed to investigate the impact of Mer
      tyrosine kinase (MerTK) during ALF and also examine how the microenvironmental
      mediator, secretory leucocyte protease inhibitor (SLPI), governs this response.
      DESIGN: Flow cytometry, immunohistochemistry, confocal imaging and gene
      expression analyses determined the phenotype, functional/transcriptomic profile
      and tissue topography of MerTK+ monocytes/macrophages in ALF, healthy and disease
      controls. The temporal evolution of macrophage MerTK expression and its impact on
      resolution was examined in APAP-induced acute liver injury using wild-type (WT)
      and Mer-deficient (Mer-/-) mice. SLPI effects on hepatic myeloid cells were
      determined in vitro and in vivo using APAP-treated WT mice. RESULTS: We
      demonstrate a significant expansion of resolution-like MerTK+HLA-DRhigh cells in
      circulatory and tissue compartments of patients with ALF. Compared with WT mice
      which show an increase of MerTK+MHCIIhigh macrophages during the resolution phase
      in ALF, APAP-treated Mer-/- mice exhibit persistent liver injury and
      inflammation, characterised by a decreased proportion of resident Kupffer cells
      and increased number of neutrophils. Both in vitro and in APAP-treated mice, SLPI
      reprogrammes myeloid cells towards resolution responses through induction of a
      MerTK+HLA-DRhigh phenotype which promotes neutrophil apoptosis and their
      subsequent clearance. CONCLUSIONS: We identify a hepatoprotective, MerTK+,
      macrophage phenotype that evolves during the resolution phase following ALF and
      represents a novel immunotherapeutic target to promote resolution responses
      following acute liver injury.

PMID- 28450391
TI  - Reactive oxygen species production induced by pore opening in cardiac
      mitochondria: The role of complex III.
AB  - Recent evidence has implicated succinate-driven reverse electron transport (RET)
      through complex I as a major source of damaging reactive oxygen species (ROS)
      underlying reperfusion injury after prolonged cardiac ischemia. However, this
      explanation may be incomplete, because RET on reperfusion is self-limiting and
      therefore transient. RET can only generate ROS when mitochondria are well
      polarized, and it ceases when permeability transition pores (PTP) open during
      reperfusion. Because prolonged ischemia/reperfusion also damages electron
      transport complexes, we investigated whether such damage could lead to ROS
      production after PTP opening has occurred. Using isolated cardiac mitochondria,
      we demonstrate a novel mechanism by which antimycin-inhibited complex III
      generates significant amounts of ROS in the presence of Mg2+ and NAD+ and the
      absence of exogenous substrates upon inner membrane pore formation by alamethicin
      or Ca2+-induced PTP opening. We show that H2O2 production under these conditions
      is related to Mg2+-dependent NADH generation by malic enzyme. H2O2 production is
      blocked by stigmatellin, indicating its origin from complex III, and by
      piericidin, demonstrating the importance of NADH-related ubiquinone reduction for
      ROS production under these conditions. For maximal ROS production, the rate of
      NADH generation has to be equal or below that of NADH oxidation, as further
      increases in [NADH] elevate ubiquinol-related complex III reduction beyond the
      optimal range for ROS generation. These results suggest that if complex III is
      damaged during ischemia, PTP opening may result in succinate/malate-fueled ROS
      production from complex III due to activation of malic enzyme by increases in
      matrix [Mg2+], [NAD+], and [ADP].

PMID- 28450390
TI  - British Society of Gastroenterology position statement on serrated polyps in the
      colon and rectum.
AB  - Serrated polyps have been recognised in the last decade as important premalignant
      lesions accounting for between 15% and 30% of colorectal cancers. There is
      therefore a clinical need for guidance on how to manage these lesions; however,
      the evidence base is limited. A working group was commission by the British
      Society of Gastroenterology (BSG) Endoscopy section to review the available
      evidence and develop a position statement to provide clinical guidance until the
      evidence becomes available to support a formal guideline. The scope of the
      position statement was wide-ranging and included: evidence that serrated lesions
      have premalignant potential; detection and resection of serrated lesions;
      surveillance strategies after detection of serrated lesions; special situations
      serrated polyposis syndrome (including surgery) and serrated lesions in colitis;
      education, audit and benchmarks and research questions. Statements on these
      issues were proposed where the evidence was deemed sufficient, and re-evaluated
      modified via a Delphi process until >80% agreement was reached. The Grading of
      Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to
      assess the strength of evidence and strength of recommendation for finalised
      statements. Key recommendation: we suggest that until further evidence on the
      efficacy or otherwise of surveillance are published, patients with sessile
      serrated lesions (SSLs) that appear associated with a higher risk of future
      neoplasia or colorectal cancer (SSLs >=10 mm or serrated lesions harbouring
      dysplasia including traditional serrated adenomas) should be offered a one-off
      colonoscopic surveillance examination at 3 years (weak recommendation, low
      quality evidence, 90% agreement).

PMID- 28450392
TI  - O-Linked N-acetylglucosamine transferase 1 regulates global histone H4
      acetylation via stabilization of the nonspecific lethal protein NSL3.
AB  - The human males absent on the first (MOF)-containing histone acetyltransferase
      nonspecific lethal (NSL) complex comprises nine subunits including the O-linked N
      acetylglucosamine (O-GlcNAc) transferase, isoform 1 (OGT1). However, whether the
      O-GlcNAc transferase activity of OGT1 controls histone acetyltransferase activity
      of the NSL complex and whether OGT1 physically interacts with the other NSL
      complex subunits remain unclear. Here, we demonstrate that OGT1 regulates the
      activity of the NSL complex by mainly acetylating histone H4 Lys-16, Lys-5, and
      Lys-8 via O-GlcNAcylation and stabilization of the NSL complex subunit NSL3.
      Knocking down or overexpressing OGT1 in human cells remarkably affected the
      global acetylation of histone H4 residues Lys-16, Lys-5, and Lys-8. Because OGT1
      is a subunit of the NSL complex, we also investigated the function of OGT1 in
      this complex. Co-transfection/co-immunoprecipitation experiments combined with in
      vitro O-GlcNAc transferase assays confirmed that OGT1 specifically binds to and O
      GlcNAcylates NSL3. In addition, wheat germ agglutinin affinity purification
      verified the occurrence of O-GlcNAc modification on NSL3 in cells. Moreover, O
      GlcNAcylation of NSL3 by wild-type OGT1 (OGT1-WT) stabilized NSL3. This
      stabilization was lost after co-transfection of NSL3 with an OGT1 mutant,
      OGT1C964A, that lacks O-GlcNAc transferase activity. Furthermore, stabilization
      of NSL3 by OGT1-WT significantly increased the global acetylation levels of H4
      Lys-5, Lys-8, and Lys-16 in cells. These results suggest that OGT1 regulates the
      activity of the NSL complex by stabilizing NSL3.

PMID- 28450393
TI  - Immunoglobulin domain interface exchange as a platform technology for the
      generation of Fc heterodimers and bispecific antibodies.
AB  - Bispecific antibodies (bsAbs) are of significant importance to the development of
      novel antibody-based therapies, and heavy chain (Hc) heterodimers represent a
      major class of bispecific drug candidates. Current technologies for the
      generation of Hc heterodimers are suboptimal and often suffer from contamination
      by homodimers posing purification challenges. Here, we introduce a new technology
      based on biomimicry wherein the protein-protein interfaces of two different
      immunoglobulin (Ig) constant domain pairs are exchanged in part or fully to
      design new heterodimeric domains. The method can be applied across Igs to design
      Fc heterodimers and bsAbs. We investigated interfaces from human IgA CH3, IgD
      CH3, IgG1 CH3, IgM CH4, T-cell receptor (TCR) alpha/beta, and TCR gamma/delta
      constant domain pairs, and we found that they successfully drive human IgG1 CH3
      or IgM CH4 heterodimerization to levels similar to or above those of reference
      methods. A comprehensive interface exchange between the TCR alpha/beta constant
      domain pair and the IgG1 CH3 homodimer was evidenced by X-ray crystallography and
      used to engineer examples of bsAbs for cancer therapy. Parental antibody pairs
      were rapidly reformatted into scalable bsAbs that were free of homodimer traces
      by combining interface exchange, asymmetric Protein A binding, and the scFv * Fab
      format. In summary, we successfully built several new CH3- or CH4-based
      heterodimers that may prove useful for designing new bsAb-based therapeutics, and
      we anticipate that our approach could be broadly implemented across the Ig
      constant domain family. To our knowledge, CH4-based heterodimers have not been
      previously reported.

PMID- 28450394
TI  - Reactive oxygen species production induced by pore opening in cardiac
      mitochondria: The role of complex II.
AB  - Succinate-driven reverse electron transport (RET) through complex I is
      hypothesized to be a major source of reactive oxygen species (ROS) that induces
      permeability transition pore (PTP) opening and damages the heart during
      ischemia/reperfusion. Because RET can only generate ROS when mitochondria are
      fully polarized, this mechanism is self-limiting once PTP opens during
      reperfusion. In the accompanying article (Korge, P., Calmettes, G., John, S. A.,
      and Weiss, J. N. (2017) J. Biol. Chem. 292, 9882-9895), we showed that ROS
      production after PTP opening can be sustained when complex III is damaged
      (simulated by antimycin). Here we show that complex II can also contribute to
      sustained ROS production in isolated rabbit cardiac mitochondria following inner
      membrane pore formation induced by either alamethicin or calcium-induced PTP
      opening. Two conditions are required to maximize malonate-sensitive ROS
      production by complex II in isolated mitochondria: (a) complex II inhibition by
      atpenin A5 or complex III inhibition by stigmatellin that results in succinate
      dependent reduction of the dicarboxylate-binding site of complex II (site IIf);
      (b) pore opening in the inner membrane resulting in rapid efflux of
      succinate/fumarate and other dicarboxylates capable of competitively binding to
      site IIf The decrease in matrix [dicarboxylate] allows O2 access to reduced site
      IIf, thereby making electron donation to O2 possible, explaining the rapid
      increase in ROS production provided that site IIf is reduced. Because ischemia is
      known to inhibit complexes II and III and increase matrix succinate/fumarate
      levels, we hypothesize that by allowing dicarboxylate efflux from the matrix, PTP
      opening during reperfusion may activate sustained ROS production by this
      mechanism after RET-driven ROS production has ceased.

PMID- 28450395
TI  - Binding of DEAD-box helicase Dhh1 to the 5'-untranslated region of ASH1 mRNA
      represses localized translation of ASH1 in yeast cells.
AB  - Local translation of specific mRNAs is regulated by dynamic changes in their
      subcellular localization, and these changes are due to complex mechanisms
      controlling cytoplasmic mRNA transport. The budding yeast Saccharomyces
      cerevisiae is well suited to studying these mechanisms because many of its
      transcripts are transported from the mother cell to the budding daughter cell.
      Here, we investigated the translational control of ASH1 mRNA after transport and
      localization. We show that although ASH1 transcripts were translated after they
      reached the bud tip, some mRNAs were bound by the RNA-binding protein Puf6 and
      were non-polysomal. We also found that the DEAD-box helicase Dhh1 complexed with
      the untranslated ASH1 mRNA and Puf6. Loss of Dhh1 affected local translation of
      ASH1 mRNA and resulted in delocalization of ASH1 transcript in the bud. Forcibly
      shifting the non-polysomal ASH1 mRNA into polysomes was associated with Dhh1
      dissociation. We further demonstrated that Dhh1 is not recruited to ASH1 mRNA co
      transcriptionally, suggesting that it could bind to ASH1 mRNA within the
      cytoplasm. Of note, Dhh1 bound to the 5'-UTR of ASH1 mRNA and inhibited its
      translation in vitro These results suggest that after localization to the bud
      tip, a portion of the localized ASH1 mRNA becomes translationally inactive
      because of binding of Dhh1 and Puf6 to the 5'- and 3'-UTRs of ASH1 mRNA.

PMID- 28450396
TI  - Heat-shock protein 90 (Hsp90) promotes opioid-induced anti-nociception by an ERK
      mitogen-activated protein kinase (MAPK) mechanism in mouse brain.
AB  - Recent advances in developing opioid treatments for pain with reduced side
      effects have focused on the signaling cascades of the MU-opioid receptor (MOR).
      However, few such signaling targets have been identified for exploitation. To
      address this need, we explored the role of heat-shock protein 90 (Hsp90) in
      opioid-induced MOR signaling and pain, which has only been studied in four
      previous articles. First, in four cell models of MOR signaling, we found that
      Hsp90 inhibition for 24 h with the inhibitor 17-N-allylamino-17
      demethoxygeldanamycin (17-AAG) had different effects on protein expression and
      opioid signaling in each line, suggesting that cell models may not be reliable
      for predicting pharmacology with this protein. We thus developed an in vivo model
      using CD-1 mice with an intracerebroventricular injection of 17-AAG for 24 h. We
      found that Hsp90 inhibition strongly blocked morphine-induced anti-nociception in
      models of post-surgical and HIV neuropathic pain but only slightly blocked anti
      nociception in a naive tail-flick model, while enhancing morphine-induced
      precipitated withdrawal. Seeking a mechanism for these changes, we found that
      Hsp90 inhibition blocks ERK MAPK activation in the periaqueductal gray and caudal
      brain stem. We tested these signaling changes by inhibiting ERK in the above
      mentioned pain models and found that ERK inhibition could account for all of the
      changes in anti-nociception induced by Hsp90 inhibition. Taken together, these
      findings suggest that Hsp90 promotes opioid-induced anti-nociception by an ERK
      mechanism in mouse brain and that Hsp90 could be a future target for improving
      the therapeutic index of opioid drugs.

PMID- 28450397
TI  - G protein-coupled estrogen receptor 1 (GPER1)/GPR30 increases ERK1/2 activity
      through PDZ motif-dependent and -independent mechanisms.
AB  - G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen
      receptor 1 (GPER1), is thought to play important roles in breast cancer and
      cardiometabolic regulation, but many questions remain about ligand activation,
      effector coupling, and subcellular localization. We showed recently that GPR30
      interacts through the C-terminal type I PDZ motif with SAP97 and protein kinase A
      (PKA)-anchoring protein (AKAP) 5, which anchor the receptor in the plasma
      membrane and mediate an apparently constitutive decrease in cAMP production
      independently of Gi/o Here, we show that GPR30 also constitutively increases
      ERK1/2 activity. Removing the receptor PDZ motif or knocking down specifically
      AKAP5 inhibited the increase, showing that this increase also requires the PDZ
      interaction. However, the increase was inhibited by pertussis toxin as well as by
      wortmannin but not by AG1478, indicating that Gi/o and phosphoinositide 3-kinase
      (PI3K) mediate the increase independently of epidermal growth factor receptor
      transactivation. FK506 and okadaic acid also inhibited the increase, implying
      that a protein phosphatase is involved. The proposed GPR30 agonist G-1 also
      increased ERK1/2 activity, but this increase was only observed at a level of
      receptor expression below that required for the constitutive increase.
      Furthermore, deleting the PDZ motif did not inhibit the G-1-stimulated increase.
      Based on these results, we propose that GPR30 increases ERK1/2 activity via two
      Gi/o-mediated mechanisms, a PDZ-dependent, apparently constitutive mechanism and
      a PDZ-independent G-1-stimulated mechanism.

PMID- 28450400
TI  - The patient's dilemma: attending the emergency department with a minor illness.

PMID- 28450399
TI  - The crystal structure of mammalian inositol 1,3,4,5,6-pentakisphosphate 2-kinase
      reveals a new zinc-binding site and key features for protein function.
AB  - Inositol 1,3,4,5,6-pentakisphosphate 2-kinases (IP5 2-Ks) are part of a family of
      enzymes in charge of synthesizing inositol hexakisphosphate (IP6) in eukaryotic
      cells. This protein and its product IP6 present many roles in cells,
      participating in mRNA export, embryonic development, and apoptosis. We reported
      previously that the full-length IP5 2-K from Arabidopsis thaliana is a zinc
      metallo-enzyme, including two separated lobes (the N- and C-lobes). We have also
      shown conformational changes in IP5 2-K and have identified the residues involved
      in substrate recognition and catalysis. However, the specific features of
      mammalian IP5 2-Ks remain unknown. To this end, we report here the first
      structure for a murine IP5 2-K in complex with ATP/IP5 or IP6 Our structural
      findings indicated that the general folding in N- and C-lobes is conserved with
      A. thaliana IP5 2-K. A helical scaffold in the C-lobe constitutes the inositol
      phosphate-binding site, which, along with the participation of the N-lobe, endows
      high specificity to this protein. However, we also noted large structural
      differences between the orthologues from these two eukaryotic kingdoms. These
      differences include a novel zinc-binding site and regions unique to the mammalian
      IP5 2-K, as an unexpected basic patch on the protein surface. In conclusion, our
      findings have uncovered distinct features of a mammalian IP5 2-K and set the
      stage for investigations into protein-protein or protein-RNA interactions
      important for IP5 2-K function and activity.

PMID- 28450401
TI  - Labour pledges pay rise for NHS staff.

PMID- 28450398
TI  - Skeletal overgrowth-causing mutations mimic an allosterically activated
      conformation of guanylyl cyclase-B that is inhibited by 2,4,6,-trinitrophenyl
      ATP.
AB  - Activating mutations in the receptor for C-type natriuretic peptide (CNP),
      guanylyl cyclase B (GC-B, also known as Npr2 or NPR-B), increase cellular cGMP
      and cause skeletal overgrowth, but how these mutations affect GTP catalysis is
      poorly understood. The A488P and R655C mutations were compared with the known
      mutation V883M. Neither mutation affected GC-B concentrations. The A488P mutation
      decreased the EC50 5-fold, increased Vmax 2.6-fold, and decreased the Km 13-fold,
      whereas the R655C mutation decreased the EC50 5-fold, increased the Vmax 2.1
      fold, and decreased the Km 4.7-fold. Neither mutation affected maximum activity
      at saturating CNP concentrations. Activation by R655C did not require disulfide
      bond formation. Surprisingly, the A488P mutant only activated the receptor when
      it was phosphorylated. In contrast, the R655C mutation converted GC-B-7A from CNP
      unresponsive to CNP-responsive. Interestingly, neither mutant was activated by
      ATP, and the Km and Hill coefficient of each mutant assayed in the absence of ATP
      were similar to those of wild-type GC-B assayed in the presence of ATP. Finally,
      1 mm 2,4,6,-trinitrophenyl ATP inhibited all three mutants by as much as 80% but
      failed to inhibit WT-GC-B. We conclude that 1) the A488P and R655C missense
      mutations result in a GC-B conformation that mimics the allosterically activated
      conformation, 2) GC-B phosphorylation is required for CNP-dependent activation by
      the A488P mutation, 3) the R655C mutation abrogates the need for phosphorylation
      in receptor activation, and 4) an ATP analog selectively inhibits the GC-B
      mutants, indicating that a pharmacologic approach could reduce GC-B dependent
      human skeletal overgrowth.

PMID- 28450402
TI  - Designing Methuselah: an ethical argument against germline genetic modification
      to prolong human longevity.
AB  - Precise editing of the human germline has been considered an unlikely and an
      unethical proposition. Recently, tools to edit the human germline have been
      developed and it is now a realistic prospect. Consequently, the ethical arguments
      around prohibiting human genome editing need to be re-evaluated. It is
      anticipatable that using it to eradicate disease-causing mutations will be
      acceptable if clinical risks can be shown to be sufficiently low. Some go further
      and advocate that genetically 'enhancing' humans will also be permissible. Here I
      argue that there are instances where human germline editing should be prohibited
      because harms can be anticipated from the results of studies of aspects of human
      psychology. The example I have chosen to illustrate this argument is prolongation
      of the human lifespan. Cohort and longitudinal studies demonstrate that a vital
      ingredient of human contentment and health is being integrated into a cohort of
      similarly aged people and experiencing life's trials and tribulations
      contemporaneously. A person genetically engineered to live longer than their
      peers will experience the loss of their cohort and many from the generation
      following them-an established risk factor for discontentment and ill health.
      Since germline genome editing precludes obtaining the consent of the individual
      in question, and that such a predictable harm will be commonly encountered, it is
      questionable that human germline editing to extend lifespan can ever be
      considered an ethical practice.

PMID- 28450403
TI  - Pathways to genetic parenthood for same-sex couples.
AB  - Researchers are pursuing various ways to synthesise human male and female
      gametes, which would be useful for people facing infertility. Some people are
      unable to conceive children with their partner because one of them is infertile
      in the sense of having an anatomical or physiological deficit. Other people-in
      same sex couples-may not be individually infertile but situationally infertile in
      relation to one another. Segers et al have described a pathway towards synthetic
      gametes that would rely on embryonic stem cells, rather than somatic cells. This
      pathway would be advantageous, they say, for same-sex couples even though it
      would not offer those couples 50%-50% shared genetics in their children but only
      50%-25%. It is unclear, however, why this approach should be preferred morally
      speaking since it represents a falling off from the kind of shared genetics in
      children that are functionally a gold standard in parents' expectations
      generally. Despite raising concerns about whether genetic relatedness is
      necessary or sufficient as a condition of parental interest in children, Segers
      et al cede the sociocultural importance of that standard. If so, same-sex couples
      seem entitled to press a case for some measure of research priority that would
      offer the same level of access to that social good as everyone else.

PMID- 28450404
TI  - Oral contraceptive use is a provoking factor for venous thromboembolism.

PMID- 28450406
TI  - Discrete mobility on the surface of glasses.

PMID- 28450407
TI  - Reply to Kinzler and Liberman: Neural correlate provides direct evidence that
      infant's social preferences are about information.

PMID- 28450405
TI  - Unique and Novel Urinary Metabolomic Features in Malignant versus Benign Adrenal
      Neoplasms.
AB  - Purpose: Adrenal incidentalomas must be differentiated from adrenocortical cancer
      (ACC). Currently, size, growth, and imaging characteristics determine the
      potential for malignancy but are imperfect. The aim was to evaluate whether
      urinary small molecules (<800 Da) are associated with ACC.Experimental Design:
      Preoperative fasting urine specimens from patients with ACC (n = 19) and benign
      adrenal tumors (n = 46) were analyzed by unbiased ultraperformance liquid
      chromatography/mass spectrometry. Creatinine-normalized features were analyzed by
      Progenesis, SIMCA, and unpaired t test adjusted by FDR. Features with an AUC >0.8
      were identified through fragmentation patterns and database searches. All lead
      features were assessed in an independent set from patients with ACC (n = 11) and
      benign adrenal tumors (n = 46) and in a subset of tissue samples from patients
      with ACC (n = 15) and benign adrenal tumors (n = 15) in the training set.Results:
      Sixty-nine features were discovered and four known metabolites identified.
      Urinary creatine riboside was elevated 2.1-fold (P = 0.0001) in patients with
      ACC. L-tryptophan, Nepsilon,Nepsilon,Nepsilon-trimethyl-L-lysine, and 3
      methylhistidine were lower 0.33-fold (P < 0.0001), 0.56-fold (P < 0.0001), and
      0.33-fold (P = 0.0003) in patients with ACC, respectively. Combined multivariate
      analysis of the four biomarkers showed an AUC of 0.89 [sensitivity 94.7%
      (confidence interval {CI}, 73.9%-99.1%), specificity 82.6% (CI, 68.6%-92.2%), PPV
      69.2% (CI, 48.2%-85.6%), and NPV 97.4% (CI, 86.5%-99.6%)] for distinguishing ACC
      from benign tumors. Of the four, creatine riboside and four unknown features were
      validated. Creatine riboside, Nepsilon,Nepsilon,Nepsilon-trimethyl-L-lysine, and
      two unknown features were elevated in ACC tumors.Conclusions: There are unique
      urinary metabolic features in patients with ACC with some metabolites present in
      patient tumor samples. Urinary creatine riboside can differentiate benign adrenal
      neoplasms from ACC. Clin Cancer Res; 23(17); 5302-10. (c)2017 AACR.

PMID- 28450408
TI  - Infants' inferences about language are social.

PMID- 28450411
TI  - Bedside manner.

PMID- 28450409
TI  - Honeybees use the skyline in orientation.
AB  - In view-based navigation, animals acquire views of the landscape from various
      locations and then compare the learned views with current views in order to
      orient in certain directions or move toward certain destinations. One landscape
      feature of great potential usefulness in view-based navigation is the skyline,
      the silhouette of terrestrial objects against the sky, as it is distant,
      relatively stable and easy to detect. The skyline has been shown to be important
      in the view-based navigation of ants, but no flying insect has yet been shown
      definitively to use the skyline in this way. Here, we show that honeybees do
      indeed orient using the skyline. A feeder was surrounded with an artificial
      replica of the natural skyline there, and the bees' departures toward the nest
      were recorded from above with a video camera under overcast skies (to eliminate
      celestial cues). When the artificial skyline was rotated, the bees' departures
      were rotated correspondingly, showing that the bees oriented by the artificial
      skyline alone. We discuss these findings in the context of the likely importance
      of the skyline in long-range homing in bees, the likely importance of altitude in
      using the skyline, the likely role of ultraviolet light in detecting the skyline,
      and what we know about the bees' ability to resolve skyline features.

PMID- 28450412
TI  - The art of medicine: arts-based training in observation and mindfulness for
      fostering the empathic response in medical residents.
AB  - Empathy is an essential attribute for medical professionals. Yet, evidence
      indicates that medical learners' empathy levels decline dramatically during
      medical school. Training in evidence-based observation and mindfulness has the
      potential to bolster the acquisition and demonstration of empathic behaviours for
      medical learners. In this prospective cohort study, we explore the impact of a
      course in arts-based visual literacy and mindfulness practice (Art of Seeing) on
      the empathic response of medical residents engaged in obstetrics and gynaecology
      and family medicine training. Following this multifaceted arts-based programme
      that integrates the facilitated viewing of art and dance, art-making, and
      mindfulness-based practices into a practitioner-patient context, 15 resident
      trainees completed the previously validated Interpersonal Reactivity Index,
      Compassion, and Mindfulness Scales. Fourteen participants also participated in
      semistructured interviews that probed their perceived impacts of the programme on
      their empathic clinical practice. The results indicated that programme
      participants improved in the Mindfulness Scale domains related to self-confidence
      and communication relative to a group of control participants following the arts
      based programme. However, the majority of the psychometric measures did not
      reveal differences between groups over the duration of the programme.
      Importantly, thematic qualitative analysis of the interview data revealed that
      the programme had a positive impact on the participants' perceived empathy
      towards colleagues and patients and on the perception of personal and
      professional well-being. The study concludes that a multifaceted arts-based
      curriculum focusing on evidence-based observation and mindfulness is a useful
      tool in bolstering the empathic response, improving communication, and fostering
      professional well-being among medical residents.

PMID- 28450413
TI  - UK spent 9.9% of GDP on healthcare last year, official figures show.

PMID- 28450415
TI  - Avoiding Preventable Complications in Hospitalized Patients with CKD.

PMID- 28450414
TI  - Adverse Outcomes Associated with Preventable Complications in Hospitalized
      Patients with CKD.
AB  - BACKGROUND: and objectives Patients with CKD are at risk of hospital-acquired
      complications (HACs). We sought to determine the association of preventable HACs
      with mortality, length of stay (LOS), and readmission. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: All adults hospitalized from April of 2003 to March
      of 2008 in Alberta were characterized by kidney function and occurrence of
      preventable HACs. CKD was defined by eGFR<60 ml/min per 1.73 m2 and/or albumin-to
      creatinine ratio >3-30 mg/mmol for >3 months in the time frame from 365 to 90
      days before admission. Regression models examined the association of HACs with
      outcomes. RESULTS: Of 536,549 hospitalizations, 8.5% (n=45,733) had CKD and 9.8%
      of patients with CKD had one or more potentially preventable HAC. In patients
      with potentially preventable HACs, proportions of death within index
      hospitalization and from discharge to 90 days were 17.7% and 6.8%, respectively.
      In patients with CKD, comparing with those hospitalizations without potentially
      preventable HACs, the adjusted odds ratio (OR) of mortality during index
      hospitalization and from hospital discharge to 90 days in patients with one or
      more preventable HAC was 4.67 (95% confidence interval [95% CI], 4.17 to 5.22)
      and 1.08 (95% CI, 0.94 to 1.25), respectively. Median incremental LOS in patients
      with one or more preventable HAC was 9.86 days (95% CI, 9.25 to 10.48). The OR
      for readmission with preventable HAC was 1.24 (95% CI, 1.15 to 1.34). In a cohort
      with and without CKD, the adjusted ORs of mortality during index hospitalization
      in patients with CKD and no preventable HACs, patients without CKD and with
      preventable HACs, and patients with CKD and preventable HACs were 2.22 (95% CI,
      1.69 to 2.94), 5.26 (95% CI, 4.98 to 5.55), and 9.56 (95% CI, 7.23 to 12.56),
      respectively (referenced to patients without CKD or preventable HACs).
      CONCLUSIONS: Preventable HACs are associated with higher mortality, incremental
      LOS, and greater risk of readmission, especially in people with CKD. Targeted
      strategies to reduce complications should be a high priority.

PMID- 28450416
TI  - "This is new and dynamic, and we are going to have to learn together".

PMID- 28450417
TI  - GDF11 Attenuates Development of Type 2 Diabetes via Improvement of Islet beta
      Cell Function and Survival.
AB  - Growth differentiation factor 11 (GDF11) has been implicated in the regulation of
      islet development and a variety of aging conditions, but little is known about
      the physiological functions of GDF11 in adult pancreatic islets. Here, we showed
      that systematic replenishment of GDF11 not only preserved insulin secretion but
      also improved the survival and morphology of beta-cells and improved glucose
      metabolism in both nongenetic and genetic mouse models of type 2 diabetes (T2D).
      Conversely, anti-GDF11 monoclonal antibody treatment caused beta-cell failure and
      lethal T2D. In vitro treatment of isolated murine islets and MIN6 cells with
      recombinant GDF11 attenuated glucotoxicity-induced beta-cell dysfunction and
      apoptosis. Mechanistically, the GDF11-mediated protective effects could be
      attributed to the activation of transforming growth factor-beta/Smad2 and
      phosphatidylinositol-4,5-bisphosphate 3-kinase-AKT-FoxO1 signaling. These
      findings suggest that GDF11 repletion may improve beta-cell function and mass and
      thus may lead to a new therapeutic approach for T2D.

PMID- 28450418
TI  - Statement of Retraction. EGFR Tyrosine Kinase Inhibitor (PD153035) Improves
      Glucose Tolerance and Insulin Action in High-Fat Diet-Fed Mice. Diabetes
      2009;58:2910-2919. DOI: 10.2337/db08-0506. PMID: 19696185.

PMID- 28450419
TI  - Phosphoproteome Analysis Reveals Differential Mode of Action of Sorafenib in
      Wildtype and Mutated FLT3 Acute Myeloid Leukemia (AML) Cells.
AB  - Constitutively activating internal tandem duplication (ITD) alterations of the
      receptor tyrosine kinase FLT3 (Fms-like tyrosine kinase 3) are common in acute
      myeloid leukemia (AML) and classifies FLT3 as an attractive therapeutic target.
      So far, applications of FLT3 small molecule inhibitors have been investigated
      primarily in FLT3-ITD+ patients. Only recently, a prolonged event-free survival
      has been observed in AML patients who were treated with the multikinase inhibitor
      sorafenib in addition to standard therapy. Here, we studied the sorafenib effect
      on proliferation in a panel of 13 FLT3-ITD- and FLT3-ITD+ AML cell lines.
      Sorafenib IC50 values ranged from 0.001 to 5.6 MUm, whereas FLT3-ITD+ cells (MOLM
      13, MV4-11) were found to be more sensitive to sorafenib than FLT3-ITD- cells.
      However, we identified two FLT3-ITD- cell lines (MONO-MAC-1 and OCI-AML-2) which
      were also sorafenib sensitive. Phosphoproteome analyses revealed that the
      affected pathways differed in sorafenib sensitive FLT3-ITD- and FLT3-ITD+ cells.
      In MV4-11 cells sorafenib suppressed mTOR signaling by direct inhibition of FLT3.
      In MONO-MAC-1 cells sorafenib inhibited the MEK/ERK pathway. These data suggest
      that the FLT3 status in AML patients might not be the only factor predicting
      response to treatment with sorafenib.

PMID- 28450420
TI  - Validation, Identification, and Biological Consequences of the Site-specific O
      GlcNAcylation Dynamics of Carbohydrate-responsive Element-binding Protein
      (ChREBP).
AB  - O-GlcNAcylation of carbohydrate-responsive element-binding protein (ChREBP) is
      believed as an important modulator of ChREBP activities, however little direct
      evidence of O-GlcNAcylation on ChREBP and no exact O-GlcNAcylation sites have
      been reported so far. Here, we validate O-GlcNAcylation on ChREBP in cell-free
      coupled transcription/translation system and in cells by chemoenzymatic and
      metabolic labeling, respectively. Moreover, for the first time, we identify O
      GlcNAcylation on Ser614 in the C-terminus of ChREBP by mass spectrometry and
      validate two important sites, Thr517 and Ser839 for O-GlcNAcylation and their
      function via molecular and chemical biological method. Under high glucose
      conditions, Ser514 phosphorylation enhances ChREBP O-GlcNAcylation, maintaining
      the transcriptional activity of ChREBP; Ser839 O-GlcNAcylation is essential for
      Mlx-heterodimerization and DNA-binding activity enhancement, consequently
      inducing transcriptional activity. Ser839 O-GlcNAcylation is also crucial for
      ChREBP nuclear export partially by strengthening interactions with CRM1 and 14-3
      3. This work is a detailed study of ChREBP O-GlcNAcylation and highlights the
      biological consequences of the site-specific O-GlcNAcylation dynamics of ChREBP.

PMID- 28450421
TI  - The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO)
      Mouse Model.
AB  - Type 2 diabetes (T2D) is a major chronic healthcare concern worldwide. Emerging
      evidence suggests that a histone-modification-mediated epigenetic mechanism
      underlies T2D. Nevertheless, the dynamics of histone marks in T2D have not yet
      been carefully analyzed. Using a mass spectrometry-based label-free and chemical
      stable isotope labeling quantitative proteomic approach, we systematically
      profiled liver histone post-translational modifications (PTMs) in a prediabetic
      high-fat diet-induced obese (DIO) mouse model. We identified 170 histone marks,
      30 of which were previously unknown. Interestingly, about 30% of the histone
      marks identified in DIO mouse liver belonged to a set of recently reported lysine
      acylation modifications, including propionylation, butyrylation, malonylation,
      and succinylation, suggesting possible roles of these newly identified histone
      acylations in diabetes and obesity. These histone marks were detected without
      prior affinity enrichment with an antibody, demonstrating that the histone
      acylation marks are present at reasonably high stoichiometry. Fifteen histone
      marks differed in abundance in DIO mouse liver compared with liver from chow-fed
      mice in label-free quantification, and six histone marks in stable isotope
      labeling quantification. Analysis of hepatic histone modifications from metformin
      treated DIO mice revealed that metformin, a drug widely used for T2D, could
      reverse DIO-stimulated histone H3K36me2 in prediabetes, suggesting that this mark
      is likely associated with T2D development. Our study thus offers a comprehensive
      landscape of histone marks in a prediabetic mouse model, provides a resource for
      studying epigenetic functions of histone modifications in obesity and T2D, and
      suggest a new epigenetic mechanism for the physiological function of metformin.

PMID- 28450423
TI  - Comparative pharmacology of a new recombinant FSH expressed by a human cell line.
AB  - Recombinant FSH proteins are important therapeutic agents for the treatment of
      infertility, including follitropin alfa expressed in Chinese Hamster Ovary (CHO)
      cells and, more recently, follitropin delta expressed in the human cell line
      PER.C6. These recombinant FSH proteins have distinct glycosylation, and have
      distinct pharmacokinetic and pharmacodynamic profiles in women. Comparative
      experiments demonstrated that follitropin delta and follitropin alfa displayed
      the same in vitro potency at the human FSH receptor, but varied in their
      pharmacokinetics in mouse and rat. While follitropin delta clearance from serum
      depended in part on the hepatic asialoglycoprotein receptor (ASGPR), follitropin
      alfa clearance was unaffected by ASGPR inhibition in rat or genetic ablation in
      mice. The distinct properties of follitropin delta and follitropin alfa are
      likely to contribute to the differing pharmacokinetic and pharmacodynamic
      profiles observed in women and to influence their efficacy in therapeutic
      protocols for the treatment of infertility.

PMID- 28450422
TI  - Characterization of a Dual Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Cancer.
AB  - The Rho GTPases Rac (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell
      division control protein 42 homolog) regulate cell functions governing cancer
      malignancy, including cell polarity, migration, and cell-cycle progression.
      Accordingly, our recently developed Rac inhibitor EHop-016 (IC50, 1,100 nmol/L)
      inhibits cancer cell migration and viability and reduces tumor growth,
      metastasis, and angiogenesis in vivo Herein, we describe MBQ-167, which inhibits
      Rac and Cdc42 with IC50 values of 103 and 78 nmol/L, respectively, in metastatic
      breast cancer cells. Consequently, MBQ-167 significantly decreases Rac and Cdc42
      downstream effector p21-activated kinase (PAK) signaling and the activity of
      STAT3, without affecting Rho, MAPK, or Akt activities. MBQ-167 also inhibits
      breast cancer cell migration, viability, and mammosphere formation. Moreover, MBQ
      167 affects cancer cells that have undergone epithelial-to-mesenchymal transition
      by a loss of cell polarity and inhibition of cell surface actin-based extensions
      to ultimately result in detachment from the substratum. Prolonged incubation (120
      hours) in MBQ-167 decreases metastatic cancer cell viability with a GI50 of
      approximately 130 nmol/L, without affecting noncancer mammary epithelial cells.
      The loss in cancer cell viability is due to MBQ-167-mediated G2-M cell-cycle
      arrest and subsequent apoptosis, especially of the detached cells. In vivo, MBQ
      167 inhibits mammary tumor growth and metastasis in immunocompromised mice by
      approximately 90%. In conclusion, MBQ-167 is 10* more potent than other currently
      available Rac/Cdc42 inhibitors and has the potential to be developed as an
      anticancer drug, as well as a dual inhibitory probe for the study of Rac and
      Cdc42. Mol Cancer Ther; 16(5); 805-18. (c)2017 AACR.

PMID- 28450424
TI  - Tetrahydrofolate Modulates Floral Transition through Epigenetic Silencing.
AB  - Folates, termed from tetrahydrofolate (THF) and its derivatives, function as
      coenzymes in one-carbon transfer reactions and play a central role in synthesis
      of nucleotides and amino acids. Dysfunction of cellular folate metabolism leads
      to serious defects in plant development; however, the molecular mechanisms of
      folate-mediated cellular modifications and physiological responses in plants are
      still largely unclear. Here, we reported that THF controls flowering time by
      adjusting DNA methylation-regulated gene expression in Arabidopsis (Arabidopsis
      thaliana). Wild-type seedlings supplied with THF as well as the high endogenous
      THF content mutant dihydrofolate synthetase folypoly-Glu synthetase homolog B
      exhibited significant up-regulation of the flowering repressor of Flowering
      Wageningen and thereby delaying floral transition in a dose-dependent manner.
      Genome-wide transcripts and DNA methylation profiling revealed that THF reduces
      DNA methylation so as to manipulate gene expression activity. Moreover, in
      accompaniment with elevated cellular ratios between monoglutamylated and
      polyglutamylated folates under increased THF levels, the content of S
      adenosylhomo-Cys, a competitive inhibitor of methyltransferases, was obviously
      higher, indicating that enhanced THF accumulation may disturb cellular
      homeostasis of the concerted reactions between folate polyglutamylation and
      folate-dependent DNA methylation. In addition, we found that the loss-of-function
      mutant of CG DNA methyltransferase MET1 displayed much less responsiveness to THF
      associated flowering time alteration. Taken together, our studies revealed a
      novel regulatory role of THF on epigenetic silencing, which will shed lights on
      the understanding of interrelations in folate homeostasis, epigenetic variation,
      and flowering control in plants.

PMID- 28450427
TI  - CD4+ T-cell Depletion Prevents GVHD.
AB  - Temporary removal of CD4+ T cells after an allogeneic hematopoietic stem-cell
      transplant leads to changes in the nature of CD8+ T cells that, according to a
      mouse study, help prevent graft-versus-host disease without jeopardizing the
      therapy's potential to eliminate leukemia or lymphoma.

PMID- 28450425
TI  - Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP
      Inhibition.
AB  - Biomarkers for more precise patient care are needed in metastatic prostate
      cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor
      olaparib in metastatic prostate cancer, demonstrating antitumor activity
      associating with homologous recombination DNA repair defects. We now report
      targeted and whole-exome sequencing of serial circulating cell-free DNA (cfDNA)
      samples collected during this trial. Decreases in cfDNA concentration
      independently associated with outcome in multivariable analyses (HR for overall
      survival at week 8: 0.19; 95% CI, 0.06-0.56; P = 0.003). All tumor tissue somatic
      DNA repair mutations were detectable in cfDNA; allele frequency of somatic
      mutations decreased selectively in responding patients (chi2P < 0.001). At
      disease progression, following response to olaparib, multiple subclonal
      aberrations reverting germline and somatic DNA repair mutations (BRCA2, PALB2)
      back in frame emerged as mechanisms of resistance. These data support the role of
      liquid biopsies as a predictive, prognostic, response, and resistance biomarker
      in metastatic prostate cancer.Significance: We report prospectively planned,
      serial, cfDNA analyses from patients with metastatic prostate cancer treated on
      an investigator-initiated phase II trial of olaparib. These analyses provide
      predictive, prognostic, response, and resistance data with "second hit" mutations
      first detectable at disease progression, suggesting clonal evolution from
      treatment-selective pressure and platinum resistance. Cancer Discov; 7(9); 1006
      17. (c)2017 AACR.See related commentary by Domchek, p. 937See related article by
      Kondrashova et al., p. 984See related article by Quigley et al., p. 999This
      article is highlighted in the In This Issue feature, p. 920.

PMID- 28450426
TI  - Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of
      BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors.
AB  - Approximately 20% of metastatic prostate cancers harbor mutations in genes
      required for DNA repair by homologous recombination repair (HRR) such as BRCA2
      HRR defects confer synthetic lethality to PARP inhibitors (PARPi) such as
      olaparib and talazoparib. In ovarian or breast cancers, olaparib resistance has
      been associated with HRR restoration, including by BRCA2 mutation reversion.
      Whether similar mechanisms operate in prostate cancer, and could be detected in
      liquid biopsies, is unclear. Here, we identify BRCA2 reversion mutations
      associated with olaparib and talazoparib resistance in patients with prostate
      cancer. Analysis of circulating cell-free DNA (cfDNA) reveals reversion mutation
      heterogeneity not discernable from a single solid-tumor biopsy and potentially
      allows monitoring for the emergence of PARPi resistance.Significance: The
      mechanisms of clinical resistance to PARPi in DNA repair-deficient prostate
      cancer have not been described. Here, we show BRCA2 reversion mutations in
      patients with prostate cancer with metastatic disease who developed resistance to
      talazoparib and olaparib. Furthermore, we show that PARPi resistance is highly
      multiclonal and that cfDNA allows monitoring for PARPi resistance. Cancer Discov;
      7(9); 999-1005. (c)2017 AACR.See related commentary by Domchek, p. 937See related
      article by Kondrashova et al., p. 984See related article by Goodall et al., p.
      1006This article is highlighted in the In This Issue feature, p. 920.

PMID- 28450428
TI  - Impact of the 5As Team study on clinical practice in primary care obesity
      management: a qualitative study.
AB  - BACKGROUND: The 5As [Ask, Assess, Advise, Agree, Assist] of Obesity Management
      Team study was a randomized controlled trial of an intervention that was
      implemented and evaluated to help primary care providers improve clinical
      practice for obesity management. This paper presents health care provider
      perspectives of the impacts of the intervention on individual provider and team
      practices. METHODS: This study reports a thematic network analysis of qualitative
      data collected during the 5As Team study, which involved 24 chronic disease teams
      affiliated with family practices in a Primary Care Network in Alberta.
      Qualitative data from 28 primary care providers (registered nurses/nurse
      practitioners [n = 14], dietitians [n = 7] and mental health workers [n = 7]) in
      the intervention arm were collected through semistructured interviews, field
      notes, practice facilitator diaries and 2 evaluation workshop questionnaires.
      RESULTS: Providers internalized 5As Team intervention concepts, deepening self
      evaluation and changing clinical reasoning around obesity. Providers perceived
      that this internalization changed the provider-patient relationship positively.
      The intervention changed relations between providers, increasing
      interdisciplinary understanding, collaboration and discovery of areas for
      improvement. This personal and interpersonal evolution effected change to the
      entire Primary Care Network. INTERPRETATION: The 5As Team intervention had
      multiple impacts on providers and teams to improve obesity management in primary
      care. Improved provider confidence and capability is a precondition of developing
      effective patient interventions. Trial registration: ClinicalTrials.gov, no.:
      NCT01967797.

PMID- 28450429
TI  - 3D T2-SPACE versus T2-FSE or T2 Gradient Recalled-Echo: Which Is the Best
      Sequence?

PMID- 28450430
TI  - Reply.

PMID- 28450431
TI  - Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple
      Sclerosis.
AB  - BACKGROUND AND PURPOSE: Potential differences between primary progressive and
      relapsing remitting multiple sclerosis are the subject of ongoing controversial
      discussions. The aim of this work was to determine whether and how primary
      progressive and relapsing-remitting multiple sclerosis subtypes differ regarding
      conventional MR imaging parameters, cerebral iron deposits, and their association
      with clinical status. MATERIALS AND METHODS: We analyzed 24 patients with primary
      progressive MS, 80 with relapsing-remitting MS, and 20 healthy controls with 1.5T
      MR imaging for assessment of the conventional quantitative parameters: T2 lesion
      load, T1 lesion load, brain parenchymal fraction, and corpus callosum volume.
      Quantitative susceptibility mapping was performed to estimate iron concentration
      in the deep gray matter. RESULTS: Decreased susceptibility within the thalamus in
      relapsing-remitting MS compared with primary-progressive MS was the only
      significant MR imaging difference between these MS subtypes. In the relapsing
      remitting MS subgroup, the Expanded Disability Status Scale score was positively
      associated with conventional parameters reflecting white matter lesions and brain
      atrophy and with iron in the putamen and caudate nucleus. A positive association
      with putaminal iron and the Expanded Disability Status Scale score was found in
      primary-progressive MS. CONCLUSIONS: Susceptibility in the thalamus might provide
      additional support for the differentiation between primary-progressive and
      relapsing-remitting MS. That the Expanded Disability Status Scale score was
      associated with conventional MR imaging parameters and iron concentrations in
      several deep gray matter regions in relapsing-remitting MS, while only a weak
      association with putaminal iron was observed in primary-progressive MS suggests
      different driving forces of disability in these MS subtypes.

PMID- 28450432
TI  - Safety and Efficacy of Aneurysm Treatment with the WEB: Results of the WEBCAST 2
      Study.
AB  - BACKGROUND AND PURPOSE: Flow disruption with the Woven EndoBridge (WEB) device is
      an innovative technique for the endovascular treatment of wide-neck bifurcation
      aneurysms. The initial version of the device (WEB Double-Layer) was evaluated in
      the WEB Clinical Assessment of IntraSaccular Aneurysm Therapy (WEBCAST) study,
      whereas the French Observatory study evaluated both WEB Double-Layer and Single
      Layer versions of the device. WEBCAST 2 was designed to evaluate the WEB Single
      Layer with Enhanced Visualization. MATERIALS AND METHODS: Patients with wide-neck
      bifurcation aneurysms for which WEB treatment was possible were included.
      Clinical data including adverse events and clinical status at 1 month and 1 year
      were collected and analyzed. A core laboratory evaluated anatomic results at 1
      year following the procedure. RESULTS: Ten European neurointerventional centers
      included 55 patients (38 women; 27-77 years of age; mean, 54.4 +/- 10.0 years)
      with 55 aneurysms. Aneurysm locations were the middle cerebral artery in 25
      aneurysms (45.5%), the anterior communicating artery in 16 (29.1%), the basilar
      artery in 9 (16.4%), and the internal carotid artery terminus in 5 (9.1%).
      Procedural morbidity and mortality at 1 month were, respectively, 1.8% (1/55
      patients) and 0.0% (0/55 patients). Morbidity and mortality at 1 year were,
      respectively, 3.9% (2/51 patients) and 2.0% (1/51 patients). At 1 year, complete
      occlusion was observed in 27/50 aneurysms (54.0%); neck remnant, in 13/50
      (26.0%); and aneurysm remnant, in 10/50 (20.0%) (adequate occlusion in 40/50,
      80.0%). CONCLUSIONS: WEBCAST 2 confirms the high safety and efficacy of WEB
      aneurysm treatment demonstrated in the WEBCAST and French Observatory studies.

PMID- 28450433
TI  - Differentiation of Enhancing Glioma and Primary Central Nervous System Lymphoma
      by Texture-Based Machine Learning.
AB  - BACKGROUND AND PURPOSE: Accurate preoperative differentiation of primary central
      nervous system lymphoma and enhancing glioma is essential to avoid unnecessary
      neurosurgical resection in patients with primary central nervous system lymphoma.
      The purpose of the study was to evaluate the diagnostic performance of a machine
      learning algorithm by using texture analysis of contrast-enhanced T1-weighted
      images for differentiation of primary central nervous system lymphoma and
      enhancing glioma. MATERIALS AND METHODS: Seventy-one adult patients with
      enhancing gliomas and 35 adult patients with primary central nervous system
      lymphomas were included. The tumors were manually contoured on contrast-enhanced
      T1WI, and the resulting volumes of interest were mined for textural features and
      subjected to a support vector machine-based machine-learning protocol. Three
      readers classified the tumors independently on contrast-enhanced T1WI. Areas
      under the receiver operating characteristic curves were estimated for each reader
      and for the support vector machine classifier. A noninferiority test for
      diagnostic accuracy based on paired areas under the receiver operating
      characteristic curve was performed with a noninferiority margin of 0.15. RESULTS:
      The mean areas under the receiver operating characteristic curve were 0.877 (95%
      CI, 0.798-0.955) for the support vector machine classifier; 0.878 (95% CI, 0.807
      0.949) for reader 1; 0.899 (95% CI, 0.833-0.966) for reader 2; and 0.845 (95% CI,
      0.757-0.933) for reader 3. The mean area under the receiver operating
      characteristic curve of the support vector machine classifier was significantly
      noninferior to the mean area under the curve of reader 1 (P = .021), reader 2 (P
      = .035), and reader 3 (P = .007). CONCLUSIONS: Support vector machine
      classification based on textural features of contrast-enhanced T1WI is
      noninferior to expert human evaluation in the differentiation of primary central
      nervous system lymphoma and enhancing glioma.

PMID- 28450434
TI  - Characterization of Extensive Microstructural Variations Associated with Punctate
      White Matter Lesions in Preterm Neonates.
AB  - BACKGROUND AND PURPOSE: Punctate white matter lesions are common in preterm
      neonates. Neurodevelopmental outcomes of the neonates are related to the degree
      of extension. This study aimed to characterize the extent of microstructural
      variations for different punctate white matter lesion grades. MATERIALS AND
      METHODS: Preterm neonates with punctate white matter lesions were divided into 3
      grades (from mild to severe: grades I-III). DTI-derived fractional anisotropy,
      axial diffusivity, and radial diffusivity between patients with punctate white
      matter lesions and controls were compared with Tract-Based Spatial Statistics and
      tract-quantification methods. RESULTS: Thirty-three preterm neonates with
      punctate white matter lesions and 33 matched controls were enrolled. There were
      15, 9, and 9 patients, respectively, in grades I, II, and III. Punctate white
      matter lesions were mainly located in white matter adjacent to the lateral
      ventricles, especially regions lateral to the trigone, posterior horns, and
      centrum semiovale and/or corona radiata. Extensive microstructural changes were
      observed in neonates with grade III punctate white matter lesions, while no
      significant changes in DTI metrics were found for grades I and II. A pattern of
      increased axial diffusivity, increased radial diffusivity, and reduced/unchanged
      fractional anisotropy was found in regions adjacent to punctate white matter
      lesion sites seen on T1WI and T2WI. Unchanged axial diffusivity, increased radial
      diffusivity, and reduced/unchanged fractional anisotropy were observed in regions
      distant from punctate white matter lesion sites. CONCLUSIONS: White matter
      microstructural variations were different across punctate white matter lesion
      grades. Extensive change patterns varied according to the distance to the lesion
      sites in neonates with severe punctate white matter lesions. These findings may
      help in determining the outcomes of punctate white matter lesions and selecting
      treatment strategies.

PMID- 28450435
TI  - Zuckerkandl Tubercle of the Thyroid Gland: Correlations between Findings of
      Anatomic Dissections and CT Imaging.
AB  - BACKGROUND AND PURPOSE: The Zuckerkandl tubercle is located at the posteromedial
      border of the thyroid lobe, and it may be confused with a neoplasm or other mass.
      This study was performed to clarify the position and morphologic characteristics
      of the Zuckerkandl tubercle by dissecting cadavers and to compare the findings
      with the corresponding CT images obtained in the same cadavers. MATERIALS AND
      METHODS: One hundred thyroid lobes from 50 fresh cadavers were dissected for this
      study (20 males and 30 females; mean age at death, 77.3 +/- 11.5 years). CT scans
      were obtained in 10 of the cadavers by using a 128-channel multidetector row CT
      scanner before dissection. RESULTS: The Zuckerkandl tubercle of the thyroid gland
      was observed in 83% of the specimens. It was mostly located at the posteromedial
      border of the thyroid lobe and within the middle two quarters (2nd and 3rd) of
      the thyroid lobe. The Zuckerkandl tubercle was classified into 3 types based on
      its direction of extension: posteromedial in 64% of the specimens, posteromedial
      and superior in 13%, and posteromedial and inferior in 6%. On axial CT, the
      Zuckerkandl tubercle was usually continuous with the posteromedial part of the
      thyroid lobe and extended posteromedially to the esophagus. The parts of the
      Zuckerkandl tubercle that protrude posteromedially and superiorly or
      posteromedially and inferiorly from the thyroid lobe appeared separated from the
      thyroid gland by a thin, low-density string on axial CT. CONCLUSIONS: Zuckerkandl
      tubercles that protrude toward the posteromedial and superior or inferior
      direction could cause confusion due to their separation when performing diagnoses
      with CT images.

PMID- 28450436
TI  - Noninvasive Assessment of IDH Mutational Status in World Health Organization
      Grade II and III Astrocytomas Using DWI and DSC-PWI Combined with Conventional MR
      Imaging.
AB  - BACKGROUND AND PURPOSE: Isocitrate dehydrogenase (IDH) has been shown to have
      both diagnostic and prognostic implications in gliomas. The purpose of this study
      was to examine whether DWI and DSC-PWI combined with conventional MR imaging
      could noninvasively predict IDH mutational status in World Health Organization
      grade II and III astrocytomas. MATERIALS AND METHODS: We retrospectively reviewed
      DWI, DSC-PWI, and conventional MR imaging in 42 patients with World Health
      Organization grade II and III astrocytomas. Minimum ADC, relative ADC, and
      relative maximum CBV values were compared between IDH-mutant and wild-type tumors
      by using the Mann-Whitney U test. Receiver operating characteristic curve and
      logistic regression were used to assess their diagnostic performances. RESULTS:
      Minimum ADC and relative ADC were significantly higher in IDH-mutated grade II
      and III astrocytomas than in IDH wild-type tumors (P < .05). Minimum ADC with the
      cutoff value of >=1.01 * 10-3 mm2/s could differentiate the mutational status
      with a sensitivity, specificity, positive predictive value, and negative
      predictive value of 76.9%, 82.6%, 91.2%, and 60.5%, respectively. The threshold
      value of <2.35 for relative maximum CBV in the prediction of IDH mutation
      provided a sensitivity, specificity, positive predictive value, and negative
      predictive value of 100.0%, 60.9%, 85.6%, and 100.0%, respectively. A combination
      of DWI, DSC-PWI, and conventional MR imaging for the identification of IDH
      mutations resulted in a sensitivity, specificity, positive predictive value, and
      negative predictive value of 92.3%, 91.3%, 96.1%, and 83.6%. CONCLUSIONS: A
      combination of conventional MR imaging, DWI, and DSC-PWI techniques produces a
      high sensitivity, specificity, positive predictive value, and negative predictive
      value for predicting IDH mutations in grade II and III astrocytomas. The strategy
      of using advanced, semiquantitative MR imaging techniques may provide an
      important, noninvasive, surrogate marker that should be studied further in
      larger, prospective trials.

PMID- 28450437
TI  - Solid Lymph Nodes as an Imaging Biomarker for Risk Stratification in Human
      Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma.
AB  - BACKGROUND AND PURPOSE: Human papillomavirus-related oropharyngeal squamous cell
      carcinoma is associated with cystic lymph nodes on CT and has a favorable
      prognosis. A subset of patients with aggressive disease experience treatment
      failure. Our aim was to determine whether the extent of cystic lymph node burden
      on staging CT can serve as an imaging biomarker to predict treatment failure in
      human papillomavirus-related oropharyngeal squamous cell carcinoma. MATERIALS AND
      METHODS: We identified patients with human papilloma virus-related oropharyngeal
      squamous cell carcinoma and staging neck CTs. Demographic and clinical variables
      were recorded. We retrospectively classified the metastatic lymph node burden on
      CT as cystic or solid and assessed radiologic extracapsular spread. Biopsy,
      subsequent imaging, or clinical follow-up was the reference standard for
      treatment failure. The primary end point was disease-free survival. Cox
      proportional hazard regression analyses of clinical, demographic, and anatomic
      variables for treatment failure were performed. RESULTS: One hundred eighty-three
      patients were included with a mean follow-up of 38 months. In univariate
      analysis, the following variables had a statistically significant association
      with treatment failure: solid-versus-cystic lymph nodes, clinical T-stage,
      clinical N-stage, and radiologic evidence of extracapsular spread. The
      multivariate Cox proportional hazard model resulted in a model that included
      solid-versus-cystic lymph nodes, T-stage, and radiologic evidence of
      extracapsular spread as independent predictors of treatment failure. Patients
      with cystic nodal metastasis at staging had significantly better disease-free
      survival than patients with solid lymph nodes. CONCLUSIONS: In human papilloma
      virus-related oropharyngeal squamous cell carcinoma, patients with solid lymph
      node metastases are at higher risk for treatment failure with worse disease-free
      survival. Solid lymph nodes may serve as an imaging biomarker to tailor
      individual treatment regimens.

PMID- 28450438
TI  - Large Basilar Apex Aneurysms Treated with Flow-Diverter Stents.
AB  - BACKGROUND AND PURPOSE: The treatment of wide-neck, large basilar apex aneurysms
      is challenging with either an endovascular or a surgical approach. The aim of the
      present study was to report our experience treating basilar apex aneurysms with
      flow-diverter stents and to evaluate their efficacy and safety profile in this
      specific anatomic condition. MATERIALS AND METHODS: We retrospectively analyzed
      data from all consecutive patients treated with flow-diverter stents at our
      institution between January 2011 and January 2015. Patients with large basilar
      apex aneurysms treated with a flow-diverter stent were included in the study.
      Clinical presentations, technical details, intra- and perioperative
      complications, and clinical and angiographic outcomes were recorded, with a
      midterm follow-up. RESULTS: Of the 175 aneurysms treated with flow-diverter
      stents at our institution, 5 patients (2 women and 3 men; age range, 44-58 years)
      received flow-diverter stent for basilar apex aneurysms. The mean follow-up after
      stent deployment was 21 months (range, 15-24 months). One patient died on day 31
      from an early postprocedural midbrain hemorrhage. One patient had a right
      cerebellar hemispheric ischemic lesion with a transient cerebellar syndrome
      resolved within 24 hours without neurologic sequelae at the latest follow-up. The
      mRS was 0 in 4 patients and 6 in 1 patient at last follow-up. CONCLUSIONS: Flow
      diversion is a feasible technique with an efficacy demonstrated at a midterm
      follow-up, especially in the case of basilar apex aneurysm recurrences after
      previous endovascular treatments. Concern about its safety profile still exists.

PMID- 28450439
TI  - Synthetic MRI for Clinical Neuroimaging: Results of the Magnetic Resonance Image
      Compilation (MAGiC) Prospective, Multicenter, Multireader Trial.
AB  - BACKGROUND AND PURPOSE: Synthetic MR imaging enables reconstruction of various
      image contrasts from 1 scan, reducing scan times and potentially providing novel
      information. This study is the first large, prospective comparison of synthetic
      versus-conventional MR imaging for routine neuroimaging. MATERIALS AND METHODS: A
      prospective multireader, multicase noninferiority trial of 1526 images read by 7
      blinded neuroradiologists was performed with prospectively acquired synthetic and
      conventional brain MR imaging case-control pairs from 109 subjects (mean, 53.0 +/
      18.5 years of age; range, 19-89 years of age) with neuroimaging indications.
      Each case included conventional T1- and T2-weighted, T1 and T2 FLAIR, and STIR
      and/or proton density and synthetic reconstructions from multiple-dynamic
      multiple-echo imaging. Images were randomized and independently assessed for
      diagnostic quality, morphologic legibility, radiologic findings indicative of
      diagnosis, and artifacts. RESULTS: Clinical MR imaging studies revealed 46
      healthy and 63 pathologic cases. Overall diagnostic quality of synthetic MR
      images was noninferior to conventional imaging on a 5-level Likert scale (P <
      .001; mean synthetic-conventional, -0.335 +/- 0.352; Delta = 0.5; lower limit of
      the 95% CI, -0.402). Legibility of synthetic and conventional morphology agreed
      in >95%, except in the posterior limb of the internal capsule for T1, T1 FLAIR,
      and proton-density views (all, >80%). Synthetic T2 FLAIR had more pronounced
      artifacts, including +24.1% of cases with flow artifacts and +17.6% cases with
      white noise artifacts. CONCLUSIONS: Overall synthetic MR imaging quality was
      similar to that of conventional proton-density, STIR, and T1- and T2-weighted
      contrast views across neurologic conditions. While artifacts were more common in
      synthetic T2 FLAIR, these were readily recognizable and did not mimic pathology
      but could necessitate additional conventional T2 FLAIR to confirm the diagnosis.

PMID- 28450440
TI  - 3D-Printed Patient-Specific Models for CT- and MRI-Guided Procedure Planning.

PMID- 28450441
TI  - Losing a partner: the varying financial and practical impacts of bereavement in
      different sociodemographic groups.
AB  - OBJECTIVES: The purpose of this study was to describe the financial and practical
      impacts of the death of a life partner, up to 5 years after bereavement. The
      study compared the impact felt by different sociodemographic groups and evaluated
      the role of financial and caring organisations in improving these impacts.
      METHODS: An evidence review of the subject area was conducted and a qualitative
      assessment of the target population (individuals whose partner had died in the
      past 3 years) was carried out using a semistructured interview (n=6).
      Subsequently, a multiple choice survey was constructed to collect data from a
      wider target population (individuals whose partner had died in the past 5 years)
      and covered topics including finances, interaction with organisations and
      management of daily tasks (n=500). RESULTS: The results of the multiple choice
      survey have been interpreted here using basic descriptive statistical analysis.
      69% of people who lost a partner were unprepared, either financially or
      practically, for bereavement. Women and those under the age of 50 experienced the
      most significant financial impact and practical changes continued beyond 3 years
      postbereavement. To manage this disruption, 61% of participants reported that
      they felt they needed more help from financial and caring organisations
      postbereavement. CONCLUSIONS: The results of this survey demonstrate some of the
      key struggles each demographic group faces immediately after bereavement and into
      the future. It is clear that preparation and bereavement support have a profound
      effect on mitigating the negative impacts seen here.

PMID- 28450443
TI  - Correction for Time-to-Credit Gender Inequities of First-Year PhD Students in the
      Biological Sciences.

PMID- 28450442
TI  - Teaching as Brain Changing: Exploring Connections between Neuroscience and
      Innovative Teaching.

PMID- 28450444
TI  - Conceptual Elements: A Detailed Framework to Support and Assess Student Learning
      of Biology Core Concepts.
AB  - The Vision and Change in Undergraduate Biology Education: Call to Action report
      has inspired and supported a nationwide movement to restructure undergraduate
      biology curricula to address overarching disciplinary concepts and competencies.
      The report outlines the concepts and competencies generally but does not provide
      a detailed framework to guide the development of the learning outcomes,
      instructional materials, and assessment instruments needed to create a reformed
      biology curriculum. In this essay, we present a detailed Vision and Change core
      concept framework that articulates key components that transcend subdisciplines
      and scales for each overarching biological concept, the Conceptual Elements (CE)
      Framework. The CE Framework was developed using a grassroots approach of
      iterative revision and incorporates feedback from more than 60 biologists and
      undergraduate biology educators from across the United States. The final
      validation step resulted in strong national consensus, with greater than 92% of
      responders agreeing that each core concept list was ready for use by the
      biological sciences community, as determined by scientific accuracy and
      completeness. In addition, we describe in detail how educators and departments
      can use the CE Framework to guide and document reformation of individual courses
      as well as entire curricula.

PMID- 28450445
TI  - The Case for Biocalculus: Design, Retention, and Student Performance.
AB  - Calculus is one of the primary avenues for initial quantitative training of
      students in all science, technology, engineering, and mathematics fields, but
      life science students have been found to underperform in the traditional calculus
      setting. As a result, and because of perceived lack of its contribution to the
      understanding of biology, calculus is being actively cut from biology program
      requirements at many institutions. Here, we present an alternative: a model for
      learning mathematics that sees the partner disciplines as crucial to student
      success. We equip faculty with information to engage in dialogue within and
      between disciplinary departments involved in quantitative education. This
      includes presenting a process for interdisciplinary development and
      implementation of biology-oriented Calculus I courses at two institutions with
      different constituents, goals, and curricular constraints. When life science
      students enrolled in these redesigned calculus courses are compared with life
      science students enrolled in traditional calculus courses, students in the
      redesigned calculus courses learn calculus concepts and skills as well as their
      traditional course peers; however, the students in the redesigned courses
      experience more authentic life science applications and are more likely to stay
      and succeed in the course than their peers who are enrolled in traditional
      courses. Therefore, these redesigned calculus courses hold promise in helping
      life science undergraduate students attain Vision and Change recommended
      competencies.

PMID- 28450446
TI  - How Question Types Reveal Student Thinking: An Experimental Comparison of
      Multiple-True-False and Free-Response Formats.
AB  - Assessments represent an important component of undergraduate courses because
      they affect how students interact with course content and gauge student
      achievement of course objectives. To make decisions on assessment design,
      instructors must understand the affordances and limitations of available question
      formats. Here, we use a crossover experimental design to identify differences in
      how multiple-true-false (MTF) and free-response (FR) exam questions reveal
      student thinking regarding specific conceptions. We report that correct response
      rates correlate across the two formats but that a higher percentage of students
      provide correct responses for MTF questions. We find that MTF questions reveal a
      high prevalence of students with mixed (correct and incorrect) conceptions, while
      FR questions reveal a high prevalence of students with partial (correct and
      unclear) conceptions. These results suggest that MTF question prompts can direct
      students to address specific conceptions but obscure nuances in student thinking
      and may overestimate the frequency of particular conceptions. Conversely, FR
      questions provide a more authentic portrait of student thinking but may face
      limitations in their ability to diagnose specific, particularly incorrect,
      conceptions. We further discuss an intrinsic tension between question structure
      and diagnostic capacity and how instructors might use multiple formats or hybrid
      formats to overcome these obstacles.

PMID- 28450447
TI  - Fair Play: A Study of Scientific Workforce Trainers' Experience Playing an
      Educational Video Game about Racial Bias.
AB  - Explicit racial bias has decreased in the United States, but racial stereotypes
      still exist and conspire in multiple ways to perpetuate the underparticipation of
      Blacks in science careers. Capitalizing on the potential effectiveness of role
      playing video games to promote the type of active learning required to increase
      awareness of and reduce subtle racial bias, we developed the video game Fair
      Play, in which players take on the role of Jamal, a Black male graduate student
      in science, who experiences discrimination in his PhD program. We describe a
      mixed-methods evaluation of the experience of scientific workforce trainers who
      played Fair Play at the National Institutes of Health Division of Training
      Workforce Development and Diversity program directors' meeting in 2013 (n = 47;
      76% female, n = 34; 53% nonwhite, n = 26). The evaluation findings suggest that
      Fair Play can promote perspective taking and increase bias literacy, which are
      steps toward reducing racial bias and affording Blacks equal opportunities to
      excel in science.

PMID- 28450448
TI  - Broadening Participation in Biology Education Research: Engaging Community
      College Students and Faculty.
AB  - Nearly half of all undergraduates are enrolled at community colleges (CCs),
      including the majority of U.S. students who represent groups underserved in the
      sciences. Yet only a small minority of studies published in discipline-based
      education research journals address CC biology students, faculty, courses, or
      authors. This marked underrepresentation of CC biology education research (BER)
      limits the availability of evidence that could be used to increase CC student
      success in biology programs. To address this issue, a diverse group of
      stakeholders convened at the Building Capacity for Biology Education Research at
      Community Colleges meeting to discuss how to increase the prevalence of CC BER
      and foster participation of CC faculty as BER collaborators and authors. The
      group identified characteristics of CCs that make them excellent environments for
      studying biology teaching and learning, including student diversity and
      institutional cultures that prioritize teaching, learning, and assessment. The
      group also identified constraints likely to impede BER at CCs: limited time,
      resources, support, and incentives, as well as misalignment between doing
      research and CC faculty identities as teachers. The meeting culminated with
      proposing strategies for faculty, administrators, journal editors, scientific
      societies, and funding agencies to better support CC BER.

PMID- 28450449
TI  - A Call to Develop Course-Based Undergraduate Research Experiences (CUREs) for
      Nonmajors Courses.
AB  - Course-based undergraduate research experiences (CUREs) for non-science majors
      (nonmajors) are potentially distinct from CUREs for developing scientists in
      their goals, learning objectives, and assessment strategies. While national calls
      to improve science, technology, engineering, and mathematics education have led
      to an increase in research revealing the positive effects of CUREs for science
      majors, less work has specifically examined whether nonmajors are impacted in the
      same way. To address this gap in our understanding, a working group focused on
      nonmajors CUREs was convened to discuss the following questions: 1) What are our
      laboratory-learning goals for nonmajors? 2) What are our research priorities to
      determine best practices for nonmajors CUREs? 3) How can we collaborate to define
      and disseminate best practices for nonmajors in CUREs? We defined three broad
      student outcomes of prime importance to the nonmajors CURE: improvement of
      scientific literacy skills, proscience attitudes, and evidence-based decision
      making. We evaluated the state of knowledge of best practices for nonmajors, and
      identified research priorities for the future. The report that follows is a
      summary of the conclusions and future directions from our discussion.

PMID- 28450450
TI  - Cancer diagnostic centres must have high throughput.

PMID- 28450451
TI  - A novel Munc13-4/S100A10/annexin A2 complex promotes Weibel-Palade body
      exocytosis in endothelial cells.
AB  - Endothelial cells respond to blood vessel injury by the acute release of the
      procoagulant von Willebrand factor, which is stored in unique secretory granules
      called Weibel-Palade bodies (WPBs). Stimulated WPB exocytosis critically depends
      on their proper recruitment to the plasma membrane, but factors involved in WPB
      plasma membrane tethering are not known. Here we identify Munc13-4, a protein
      mutated in familial hemophagocytic lymphohistiocytosis 3, as a WPB-tethering
      factor. Munc13-4 promotes histamine-evoked WPB exocytosis and is present on WPBs,
      and secretagogue stimulation triggers an increased recruitment of Munc13-4 to
      WPBs and a clustering of Munc13-4 at sites of WPB-plasma membrane contact. We
      also identify the S100A10 subunit of the annexin A2 (AnxA2)-S100A10 protein
      complex as a novel Munc13-4 interactor and show that AnxA2-S100A10 participates
      in recruiting Munc13-4 to WPB fusion sites. These findings indicate that Munc13-4
      supports acute WPB exocytosis by tethering WPBs to the plasma membrane via AnxA2
      S100A10.

PMID- 28450452
TI  - Nanonet force microscopy for measuring forces in single smooth muscle cells of
      the human aorta.
AB  - A number of innovative methods exist to measure cell-matrix adhesive forces, but
      they have yet to accurately describe and quantify the intricate interplay of a
      cell and its fibrous extracellular matrix (ECM). In cardiovascular pathologies,
      such as aortic aneurysm, new knowledge on the involvement of cell-matrix forces
      could lead to elucidation of disease mechanisms. To better understand this
      dynamics, we measured primary human aortic single smooth muscle cell (SMC) forces
      using nanonet force microscopy in both inside-out (I-O intrinsic contractility)
      and outside-in (O-I external perturbation) modes. For SMC populations, we
      measured the I-O and O-I forces to be 12.9 +/- 1.0 and 57.9 +/- 2.5 nN,
      respectively. Exposure of cells to oxidative stress conditions caused a force
      decrease of 57 and 48% in I-O and O-I modes, respectively, and an increase in
      migration rate by 2.5-fold. Finally, in O-I mode, we cyclically perturbed cells
      at constant strain of varying duration to simulate in vivo conditions of the
      cardiac cycle and found that I-O forces decrease with increasing duration and O-I
      forces decreased by half at shorter cycle times. Thus our findings highlight the
      need to study forces exerted and felt by cells simultaneously to comprehensively
      understand force modulation in cardiovascular disease.

PMID- 28450453
TI  - Microtubule dynamics drive enhanced chromatin motion and mobilize telomeres in
      response to DNA damage.
AB  - Chromatin exhibits increased mobility on DNA damage, but the biophysical basis
      for this behavior remains unknown. To explore the mechanisms that drive DNA
      damage-induced chromosome mobility, we use single-particle tracking of tagged
      chromosomal loci during interphase in live yeast cells together with polymer
      models of chromatin chains. Telomeres become mobilized from sites on the nuclear
      envelope and the pericentromere expands after exposure to DNA-damaging agents.
      The magnitude of chromatin mobility induced by a single double-strand break
      requires active microtubule function. These findings reveal how relaxation of
      external tethers to the nuclear envelope and internal chromatin-chromatin
      tethers, together with microtubule dynamics, can mobilize the genome in response
      to DNA damage.

PMID- 28450454
TI  - Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes.
AB  - Sortilin is a multiligand sorting receptor responsible for the anterograde
      transport of lysosomal enzymes and substrates. Here we demonstrate that sortilin
      is also involved in retrograde protein traffic. In cultured 3T3-L1 adipocytes,
      sortilin together with retromer rescues Glut4 from degradation in lysosomes and
      retrieves it to the TGN, where insulin--responsive vesicles are formed.
      Mechanistically, the luminal Vps10p domain of sortilin interacts with the first
      luminal loop of Glut4, and the cytoplasmic tail of sortilin binds to retromer.
      Ablation of the retromer does not affect insulin signaling but decreases the
      stability of sortilin and Glut4 and blocks their entry into the small vesicular
      carriers. As a result, Glut4 cannot reach the insulin-responsive compartment, and
      insulin-stimulated glucose uptake in adipocytes is suppressed. We suggest that
      sortilin- and retromer-mediated Glut4 retrieval from endosomes may represent a
      step in the Glut4 pathway vulnerable to the development of insulin resistance and
      diabetes.

PMID- 28450455
TI  - MAARS: a novel high-content acquisition software for the analysis of mitotic
      defects in fission yeast.
AB  - Faithful segregation of chromosomes during cell division relies on multiple
      processes such as chromosome attachment and correct spindle positioning. Yet
      mitotic progression is defined by multiple parameters, which need to be
      quantitatively evaluated. To study the spatiotemporal control of mitotic
      progression, we developed a high-content analysis (HCA) approach that combines
      automated fluorescence microscopy with real-time quantitative image analysis and
      allows the unbiased acquisition of multiparametric data at the single-cell level
      for hundreds of cells simultaneously. The Mitotic Analysis and Recording System
      (MAARS) provides automatic and quantitative single-cell analysis of mitotic
      progression on an open-source platform. It can be used to analyze specific
      characteristics such as cell shape, cell size, metaphase/anaphase delays, and
      mitotic abnormalities including spindle mispositioning, spindle elongation
      defects, and chromosome segregation defects. Using this HCA approach, we were
      able to visualize rare and unexpected events of error correction during anaphase
      in wild-type or mutant cells. Our study illustrates that such an expert system of
      mitotic progression is able to highlight the complexity of the mechanisms
      required to prevent chromosome loss during cell division.

PMID- 28450456
TI  - Temporal cascade of inflammatory cytokines and cell-type populations in monocyte
      chemotactic protein-1 (MCP-1)-mediated aneurysm healing.
AB  - BACKGROUND: We have previously shown that monocyte chemotactic protein-1 (MCP-1)
      promotes aneurysm healing. OBJECTIVE: To determine the temporal cascade and
      durability of aneurysm healing. METHODS: Murine carotid aneurysms were treated
      with MCP-1-releasing or poly(lactic-co-glycolic) acid (PLGA)-only coils. Aneurysm
      healing was assessed by quantitative measurements of intraluminal tissue ingrowth
      on 5 MUm sections by blinded observers. RESULTS: Aneurysm healing occurred in
      stages characteristic of normal wound healing. The 1st stage (day 3) was
      characterized by a spike in neutrophils and T cells. The 2nd stage (week 1) was
      characterized by an influx of macrophages and CD45+ cells significantly greater
      with MCP-1 than with PLGA (p<0.05). The third stage (week 2-3) was characterized
      by proliferation of smooth muscle cells and fibroblasts (greater with MCP-1 than
      with PLGA, p<0.05). The fourth stage (3-6 months) was characterized by leveling
      off of smooth muscle cells and fibroblasts. M1 macrophages were greater at week
      1, whereas M2 macrophages were greater at weeks 2 and 3 with MCP-1 than with
      PLGA. Interleukin 6 was present early and increased through week 2 (p<0.05
      compared with PLGA) then decreased and leveled off through 6 months. Tumour
      necrosis factor alpha was present early and remained constant through 6 months.
      MCP-1 and PLGA treatment had similar rates of tissue ingrowth at early time
      points, but MCP-1 had a significantly greater tissue ingrowth at week 3 (p<0.05),
      which persisted for 6 months. CONCLUSIONS: The sequential cascade is consistent
      with an inflammatory model of injury, repair, and remodeling.

PMID- 28450457
TI  - Roles for the Rad27 Flap Endonuclease in Mitochondrial Mutagenesis and Double
      Strand Break Repair in Saccharomyces cerevisiae.
AB  - The structure-specific nuclease, Rad27p/FEN1, plays a crucial role in DNA repair
      and replication mechanisms in the nucleus. Genetic assays using the rad27-?
      mutant have shown altered rates of DNA recombination, microsatellite instability,
      and point mutation in mitochondria. In this study, we examined the role of Rad27p
      in mitochondrial mutagenesis and double-strand break (DSB) repair in
      Saccharomyces cerevisiae Our findings show that Rad27p is essential for efficient
      mitochondrial DSB repair by a pathway that generates deletions at a region
      flanked by direct repeat sequences. Mutant analysis suggests that both
      exonuclease and endonuclease activities of Rad27p are required for its role in
      mitochondrial DSB repair. In addition, we found that the nuclease activities of
      Rad27p are required for the prevention of mitochondrial DNA (mtDNA) point
      mutations, and in the generation of spontaneous mtDNA rearrangements. Overall,
      our findings underscore the importance of Rad27p in the maintenance of mtDNA, and
      demonstrate that it participates in multiple DNA repair pathways in mitochondria,
      unlinked to nuclear phenotypes.

PMID- 28450458
TI  - The Mitotic Exit Network Regulates Spindle Pole Body Selection During Sporulation
      of Saccharomyces cerevisiae.
AB  - Age-based inheritance of centrosomes in eukaryotic cells is associated with
      faithful chromosome distribution in asymmetric cell divisions. During
      Saccharomyces cerevisiae ascospore formation, such an inheritance mechanism
      targets the yeast centrosome equivalents, the spindle pole bodies (SPBs) at
      meiosis II onset. Decreased nutrient availability causes initiation of spore
      formation at only the younger SPBs and their associated genomes. This mechanism
      ensures encapsulation of nonsister genomes, which preserves genetic diversity and
      provides a fitness advantage at the population level. Here, by usage of an
      enhanced system for sporulation-induced protein depletion, we demonstrate that
      the core mitotic exit network (MEN) is involved in age-based SPB selection.
      Moreover, efficient genome inheritance requires Dbf2/20-Mob1 during a late step
      in spore maturation. We provide evidence that the meiotic functions of the MEN
      are more complex than previously thought. In contrast to mitosis, completion of
      the meiotic divisions does not strictly rely on the MEN whereas its activity is
      required at different time points during spore development. This is reminiscent
      of vegetative MEN functions in spindle polarity establishment, mitotic exit, and
      cytokinesis. In summary, our investigation contributes to the understanding of
      age-based SPB inheritance during sporulation of S. cerevisiae and provides
      general insights on network plasticity in the context of a specialized
      developmental program. Moreover, the improved system for a developmental-specific
      tool to induce protein depletion will be useful in other biological contexts.

PMID- 28450459
TI  - Experimental Evolution Reveals Favored Adaptive Routes to Cell Aggregation in
      Yeast.
AB  - Yeast flocculation is a community-building cell aggregation trait that is an
      important mechanism of stress resistance and a useful phenotype for brewers;
      however, it is also a nuisance in many industrial processes, in clinical
      settings, and in the laboratory. Chemostat-based evolution experiments are
      impaired by inadvertent selection for aggregation, which we observe in 35% of
      populations. These populations provide a testing ground for understanding the
      breadth of genetic mechanisms Saccharomyces cerevisiae uses to flocculate, and
      which of those mechanisms provide the biggest adaptive advantages. In this study,
      we employed experimental evolution as a tool to ask whether one or many routes to
      flocculation are favored, and to engineer a strain with reduced flocculation
      potential. Using a combination of whole genome sequencing and bulk segregant
      analysis, we identified causal mutations in 23 independent clones that had
      evolved cell aggregation during hundreds of generations of chemostat growth. In
      12 of those clones, we identified a transposable element insertion in the
      promoter region of known flocculation gene FLO1, and, in an additional five
      clones, we recovered loss-of-function mutations in transcriptional repressor
      TUP1, which regulates FLO1 and other related genes. Other causal mutations were
      found in genes that have not been previously connected to flocculation. Evolving
      a flo1 deletion strain revealed that this single deletion reduces flocculation
      occurrences to 3%, and demonstrated the efficacy of using experimental evolution
      as a tool to identify and eliminate the primary adaptive routes for undesirable
      traits.

PMID- 28450460
TI  - Genotypic Complexity of Fisher's Geometric Model.
AB  - Fisher's geometric model was originally introduced to argue that complex
      adaptations must occur in small steps because of pleiotropic constraints. When
      supplemented with the assumption of additivity of mutational effects on
      phenotypic traits, it provides a simple mechanism for the emergence of genotypic
      epistasis from the nonlinear mapping of phenotypes to fitness. Of particular
      interest is the occurrence of reciprocal sign epistasis, which is a necessary
      condition for multipeaked genotypic fitness landscapes. Here we compute the
      probability that a pair of randomly chosen mutations interacts sign
      epistatically, which is found to decrease with increasing phenotypic dimension n,
      and varies nonmonotonically with the distance from the phenotypic optimum. We
      then derive expressions for the mean number of fitness maxima in genotypic
      landscapes comprised of all combinations of L random mutations. This number
      increases exponentially with L, and the corresponding growth rate is used as a
      measure of the complexity of the landscape. The dependence of the complexity on
      the model parameters is found to be surprisingly rich, and three distinct phases
      characterized by different landscape structures are identified. Our analysis
      shows that the phenotypic dimension, which is often referred to as phenotypic
      complexity, does not generally correlate with the complexity of fitness
      landscapes and that even organisms with a single phenotypic trait can have
      complex landscapes. Our results further inform the interpretation of experiments
      where the parameters of Fisher's model have been inferred from data, and help to
      elucidate which features of empirical fitness landscapes can be described by this
      model.

PMID- 28450462
TI  - Increase paediatric trainee numbers to meet workforce shortfall, says Royal
      College.

PMID- 28450461
TI  - Identification of Ceruloplasmin as a Gene that Affects Susceptibility to
      Glomerulonephritis Through Macrophage Function.
AB  - Crescentic glomerulonephritis (Crgn) is a complex disorder where macrophage
      activity and infiltration are significant effector causes. In previous linkage
      studies using the uniquely susceptible Wistar Kyoto (WKY) rat strain, we have
      identified multiple crescentic glomerulonephritis QTL (Crgn) and positionally
      cloned genes underlying Crgn1 and Crgn2, which accounted for 40% of total
      variance in glomerular inflammation. Here, we have generated a backcross (BC)
      population (n = 166) where Crgn1 and Crgn2 were genetically fixed and found
      significant linkage to glomerular crescents on chromosome 2 (Crgn8, LOD = 3.8).
      Fine mapping analysis by integration with genome-wide expression QTLs (eQTLs)
      from the same BC population identified ceruloplasmin (Cp) as a positional eQTL in
      macrophages but not in serum. Liquid chromatography-tandem mass spectrometry
      confirmed Cp as a protein QTL in rat macrophages. WKY macrophages overexpress Cp
      and its downregulation by RNA interference decreases markers of glomerular
      proinflammatory macrophage activation. Similarly, short incubation with Cp
      results in a strain-dependent macrophage polarization in the rat. These results
      suggest that genetically determined Cp levels can alter susceptibility to Crgn
      through macrophage function and propose a new role for Cp in early macrophage
      activation.

PMID- 28450463
TI  - What does patient feedback reveal about the NHS? A mixed methods study of
      comments posted to the NHS Choices online service.
AB  - OBJECTIVE: To examine the key themes of positive and negative feedback in
      patients' online feedback on NHS (National Health Service) services in England
      and to understand the specific issues within these themes and how they drive
      positive and negative evaluation. DESIGN: Computer-assisted quantitative and
      qualitative studies of 228 113 comments (28 971 142 words) of online feedback
      posted to the NHS Choices website. Comments containing the most frequent positive
      and negative evaluative words are qualitatively examined to determine the key
      drivers of positive and negative feedback. PARTICIPANTS: Contributors posting
      comments about the NHS between March 2013 and September 2015. RESULTS: Overall,
      NHS services were evaluated positively approximately three times more often than
      negatively. The four key areas of focus were: treatment, communication,
      interpersonal skills and system/organisation. Treatment exhibited the highest
      proportion of positive evaluative comments (87%), followed by communication
      (77%), interpersonal skills (44%) and, finally, system/organisation (41%).
      Qualitative analysis revealed that reference to staff interpersonal skills
      featured prominently, even in comments relating to treatment and
      system/organisational issues. Positive feedback was elicited in cases of staff
      being caring, compassionate and knowing patients'' names, while rudeness, apathy
      and not listening were frequent drivers of negative feedback. CONCLUSIONS:
      Although technical competence constitutes an undoubtedly fundamental aspect of
      healthcare provision, staff members were much more likely to be evaluated both
      positively and negatively according to their interpersonal skills. Therefore, the
      findings reported in this study highlight the salience of such 'soft' skills to
      patients and emphasise the need for these to be focused upon and developed in
      staff training programmes, as well as ensuring that decisions around NHS funding
      do not result in demotivated and rushed staff. The findings also reveal a
      significant overlap between the four key themes in the ways that care is
      evaluated by patients.

PMID- 28450465
TI  - Immunisation coverage of children in the child welfare system: a systematic
      review protocol.
AB  - INTRODUCTION: Children may be placed in the care of the child welfare system when
      they require additional supports or intervention to ensure their safety and
      security. Transitions in living arrangements (eg, home to foster care and return
      to home) and other difficult circumstances for these children may result in
      interruptions in routine preventive healthcare, such as childhood immunisations.
      The purpose of this systematic literature review is to determine whether
      immunisation coverage is a problem among children in the child welfare system and
      identify any known supports and/or barriers to vaccine uptake in this population.
      METHODS AND ANALYSIS: This systematic review will encompass published and
      unpublished primary research studies that assess (A) immunisation coverage of
      children in the child welfare system, (B) how this coverage compares to the
      general population and/or children not in the child welfare system, and (C)
      supports and barriers affecting immunisation status of these children. Vaccines
      in the recommended childhood immunisation schedule for each study setting will be
      considered. Medline, Embase, Cochrane Library, CINAHL, SocINDEX and ERIC will be
      comprehensively searched. We will also search ProQuest dissertations and theses,
      the Conference Proceedings Citation Index for Science and Social Science &
      Humanities, and a sample of relevant provincial, national and international
      websites. References of included studies will be manually searched for relevant
      studies. English language primary studies from 2000 to current focused on
      immunisations of children (age 0-17 years) in the child welfare system, in a high
      income country, will be included. A narrative analysis of key findings from
      included studies will be performed and presented. ETHICS AND DISSEMINATION: This
      protocol does not require ethics approval. Planned dissemination includes peer
      reviewed publication, conference presentations and briefs for policy makers.
      TRIAL REGISTRATION NUMBER: This protocol is registered in the PROSPERO
      International Prospective Register of Systematic Reviews, registration number
      CRD42016047319.

PMID- 28450464
TI  - Positive percentages of urine morphine tests among methadone maintenance
      treatment clients with HIV/AIDS: a 12-month follow-up study in Guangdong
      Province, China.
AB  - OBJECTIVE: We aimed to assess the positive percentages of urine morphine tests
      and correlates among methadone maintenance treatment (MMT) clients with HIV/AIDS
      in Guangdong, China. SETTING: Fourteen MMT clinics located in nine cities of
      Guangdong were chosen as study sites. PARTICIPANTS: In this study, we reviewed
      293 clients with opioid dependence, who were HIV seropositive, 18 years or older,
      provided informed consent and had at least 10 records of urine morphine tests
      during the study period. PRIMARY AND SECONDARY OUTCOME MEASURES: The positive
      percentages of urine morphine tests were calculated and underlying predictors
      were estimated. RESULTS: The highest positive percentage (95.9%) was observed in
      the first month. After excluding the highest percentage in the first month, the
      average positive percentage was 40.9% for month 2 to month 12. Positive
      percentages of urine morphine tests that were <20%, 20-60% and >80% were 25.4%,
      36.1% and 38.5% respectively. Lower percentages of continued heroin use were
      associated with being young (OR<=30=0.31, 95% CI 0.12 to 0.78; OR31-=0.44, 95% CI
      0.20 to 1.00), and financial sources depending on family or friends (OR=0.55, 95%
      CI 0.32 to 0.93). Higher percentages of continued heroin use were associated with
      being unemployed (OR=1.99, 95% CI 1.13 to 3.49) and poor MMT attendance
      (OR<20%=3.60, 95% CI 1.55 to 8.33; OR20%-=2.80, 95% CI 1.48 to 5.33).
      CONCLUSIONS: High positive percentages of urine morphine tests remain prevalent
      among MMT clients with HIV/AIDS in Guangdong. The present findings have
      implications for taking effective measures to facilitate attendance in order to
      decrease heroin use and ultimately improve the effectiveness among these sub
      group MMT clients.

PMID- 28450466
TI  - Improving teaching about medically unexplained symptoms for newly qualified
      doctors in the UK: findings from a questionnaire survey and expert workshop.
AB  - OBJECTIVES: Medically unexplained symptoms (MUS) present frequently in
      healthcare, can be complex and frustrating for clinicians and patients and are
      often associated with overinvestigation and significant costs. Doctors need to be
      aware of appropriate management strategies for such patients early in their
      training. A previous qualitative study with foundation year doctors (junior
      doctors in their first 2 years postqualification) indicated significant lack of
      knowledge about this topic and appropriate management strategies. This study
      reviewed whether, and in what format, UK foundation training programmes for newly
      qualified doctors include any teaching about MUS and sought recommendations for
      further development of such training. DESIGN: Mixed-methods design comprising a
      web-based questionnaire survey and an expert consultation workshop. SETTING:
      Nineteen foundation schools in England, Wales and Northern Ireland PARTICIPANTS:
      Questionnaire administered via email to 155 foundation training programme
      directors (FTPDs) attached to the 19 foundation schools, followed by an expert
      consultation workshop attended by 13 medical educationalists, FTPDs and junior
      doctors. RESULTS: The 53/155 (34.2%) FTPDs responding to the questionnaire
      represented 15 of the 19 foundation schools, but only 6/53 (11%) reported any
      current formal teaching about MUS within their programmes. However, most
      recognised the importance of providing such teaching, suggesting 2-3 hours per
      year. All those attending the expert consultation workshop recommended case-based
      discussions, role-play and the use of videos to illustrate positive and negative
      examples of doctor-patient interactions as educational methods of choice.
      Educational sessions should cover the skills needed to provide appropriate
      explanations for patients' symptoms as well as avoid unnecessary investigations,
      and providing information about suitable treatment options. CONCLUSIONS: There is
      an urgent need to improve foundation level training about MUS, as current
      provision is very limited. An interactive approach covering a range of topics is
      recommended, but must be delivered within a realistic time frame for the
      curriculum.

PMID- 28450467
TI  - Quality of reporting in abstracts of RCTs published in emergency medicine
      journals: a protocol for a systematic survey of the literature.
AB  - INTRODUCTION: The quality of reporting of abstracts of randomised controlled
      trials (RCTs) in major general medical journals and in some category-specific
      journals was shown to be poor before the publication of the ConsolidatedStandards
      of ReportingTrials (CONSORT) extension for abstracts in 2008, and an improvement
      in the quality of reporting of abstracts was observed after its publication. The
      effect of the publication of the CONSORT extension for abstracts on the quality
      of reporting of RCTs in emergency medicine journals has not been studied. In this
      paper, we present the protocol of a systematic survey of the literature, aimed at
      assessing the quality of reporting in abstracts of RCTs published in emergency
      medicine journals and at evaluating the effect of the publication of the CONSORT
      extension for abstracts on the quality of reporting. METHODS AND ANALYSIS: The
      Medline database will be searched for RCTs published in the years 2005-2007 and
      2014-2015 in the top 10 emergency medicine journals, according to their impact
      factor. Candidate studies will be screened for inclusion in the review. Exclusion
      criteria will be the following: the abstract is not available, they are published
      only as abstracts, still recruiting, or duplicate publications. The study
      outcomes will be the overall quality of reporting (number of items reported)
      according to the CONSORT extension and the compliance with its individual items.
      Two independent reviewers will screen each article for inclusion and will extract
      data on the CONSORT items and on other variables, which can possibly affect the
      quality of reporting. ETHICS AND DISSEMINATION: This is a library-based study and
      therefore exempt from research ethics board review. The review results will be
      disseminated through abstract submission to conferences and publication in a peer
      reviewed biomedical journal.

PMID- 28450468
TI  - Barriers to evidence-based acute stroke care in Ghana: a qualitative study on the
      perspectives of stroke care professionals.
AB  - OBJECTIVE: Despite major advances in research on acute stroke care interventions,
      relatively few stroke patients benefit from evidence-based care due to multiple
      barriers. Yet current evidence of such barriers is predominantly from high-income
      countries. This study seeks to understand stroke care professionals' views on the
      barriers which hinder the provision of optimal acute stroke care in Ghanaian
      hospital settings. DESIGN: A qualitative approach using semistructured
      interviews. Both thematic and grounded theory approaches were used to analyse and
      interpret the data through a synthesis of preidentified and emergent themes.
      SETTING: A multisite study, conducted in six major referral acute hospital
      settings (three teaching and three non-teaching regional hospitals) in Ghana.
      PARTICIPANTS: A total of 40 participants comprising neurologists, emergency
      physician specialists, non-specialist medical doctors, nurses, physiotherapists,
      clinical psychologists and a dietitian. RESULTS: Four key barriers and 12
      subthemes of barriers were identified. These include barriers at the patient
      (financial constraints, delays, sociocultural or religious practices, discharge
      against medical advice, denial of stroke), health system (inadequate medical
      facilities, lack of stroke care protocol, limited staff numbers, inadequate staff
      development opportunities), health professionals (poor collaboration, limited
      knowledge of stroke care interventions) and broader national health policy (lack
      of political will) levels. Perceived barriers varied across health professional
      disciplines and hospitals. CONCLUSION: Barriers from low/middle-income countries
      differ substantially from those in high-income countries. For evidence-based
      acute stroke care in low/middle-income countries such as Ghana, health policy
      makers and hospital managers need to consider the contrasts and uniqueness in
      these barriers in designing quality improvement interventions to optimise patient
      outcomes.

PMID- 28450470
TI  - New microbleed after blood-brain barrier leakage in intracerebral haemorrhage.
AB  - Cerebral microbleeds are increasingly recognised as biomarkers of small vessel
      disease. Several preclinical and clinical studies have suggested that chronic
      disruption of the blood-brain barrier is one of the mechanisms for the
      development of cerebral microbleeds.A 51-year-old man experienced two left
      parieto-occipital lobar intracerebral haemorrhages (ICHs) in the timespan of 2
      years. Multiple microbleeds surrounding the two haemorrhages were found on MRI,
      but not at location distant from the haemorrhages. Ten months after the last
      haemorrhage, an MRI demonstrated a right occipital focus of contrast enhancement.
      Twenty months after the last ICH, a new cerebral microbleed had developed exactly
      at the location of the earlier contrast enhancement.This case demonstrates that
      blood-brain barrier disruption may be an important factor preceding the
      development of cerebral microbleeds.

PMID- 28450469
TI  - Novel Phosphodiesterase 4 Inhibitor FCPR03 Alleviates Lipopolysaccharide-Induced
      Neuroinflammation by Regulation of the cAMP/PKA/CREB Signaling Pathway and NF
      kappaB Inhibition.
AB  - Overactivation of microglia contributes to the induction of neuroinflammation,
      which is highly involved in the pathology of many neurodegenerative diseases.
      Phosphodiesterase 4 (PDE4) represents a promising therapeutic target for anti
      inflammation; however, the dose-limiting side effects, such as nausea and emesis,
      have impeded their clinic application. FCPR03, a novel selective PDE4 inhibitor
      synthesized in our laboratory, shows little or no emetic potency; however, the
      anti-inflammatory activities of FCPR03 in vitro and in vivo and the molecular
      mechanisms are still not clearly understood. This study was undertaken to
      delineate the anti-inflammatory effects of FCPR03 both in vitro and in vivo and
      explore whether these effects are regulated by PDE4-mediated signaling pathway.
      BV-2 microglial cells stimulated by lipopolysaccharide (LPS) and mice injected
      i.p. with LPS were established as in vitro and in vivo models of inflammation.
      Our results showed that FCPR03 dose dependently suppressed the production of
      tumor necrosis factor alpha, interleukin-1beta, and iinterleukin-6 in BV-2
      microglial cells treated with LPS. The role of FCPR03 in the production of
      proinflammatory factors was reversed by pretreatment with protein kinase A (PKA)
      inhibitor H89. In addition, FCPR03 reduced the levels of proinflammatory factors
      in the hippocampus and cortex of mice injected with LPS. Our results further
      demonstrated that FCPR03 effectively increased the production of cAMP, promoted
      cAMP response element binding protein (CREB) phosphorylation, and inhibited
      nuclear factor kappaB (NF-kappaB) activation both in vitro and in vivo. Our
      findings suggest that FCPR03 inhibits the neuroinflammatory response through the
      activation of cAMP/PKA/CREB signaling pathway and NF-kappaB inhibition.

PMID- 28450471
TI  - Leiomyosarcoma: a rare but fatal tumour of the inferior vena cava.

PMID- 28450475
TI  - Insurance claims analysis sheds more light on the health problems of
      brachycephalic dogs.

PMID- 28450472
TI  - Paneth-cell-disruption-induced necrotizing enterocolitis in mice requires live
      bacteria and occurs independently of TLR4 signaling.
AB  - Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and
      mortality in premature infants. Both human surgical specimens and animal models
      suggest a potential involvement of Paneth cells in NEC pathogenesis. Paneth cells
      play critical roles in epithelial homeostasis, innate immunity and host-microbial
      interactions. Yet, the complex interplay between Paneth cell disruption,
      epithelial barrier dysfunction and microbial-driven inflammation remains unclear
      in the immature intestine. In this study, mucosal intestinal injury consistent
      with human NEC was induced in postnatal day 14-16 (P14-P16) mice by disrupting
      Paneth cells, followed by gavage with Klebsiella pneumonia. Mucosal injury was
      determined by histology, serum cytokine levels and epithelial barrier
      dysfunction. Toll-like receptor 4 (TLR4) activation was examined using protein
      expression, gene expression, and TLR4-/- mice. Finally, the role of bacteria was
      evaluated using heat-killed bacteria, conditioned media, Bacillus cereus and
      cecal slurries. We found that live bacteria were required to induce injury;
      however, TLR4 activation was not required. NEC induced by Paneth cell disruption
      results in altered localization of tight junction proteins and subsequent loss of
      barrier function. Prior research has shown a requirement for TLR4 activation to
      induce NEC-like damage. However, many infants develop NEC in the absence of Gram
      negative rod bacteremia, raising the possibility that alternative pathways to
      intestinal injury exist. In this study, we show a previously unknown mechanism
      for the development of intestinal injury equivalent to that seen in human NEC and
      that is not dependent on TLR4 pathways. These data are congruent with the new
      hypothesis that NEC may be the consequence of several disease processes ending in
      a final common inflammatory pathway.

PMID- 28450478
TI  - 'It's time to do the right thing for our patients. Let's leave the ego at the
      door'.

PMID- 28450479
TI  - Judges humbled by lengths to which people go to improve animals' lives.

PMID- 28450485
TI  - Outbreak of toe tip necrosis syndrome in calves.
AB  - Toe tip necrosis syndrome in calvesAbortions in embryo recipient gimmers
      associated with Paecilomyces variotiiAmyloidosis secondary to dosing gun injury
      in a eweRhinitis and middle ear infection in pigsFungal pneumonia in a duckThese
      are among matters discussed in the disease surveillance report for January 2017
      from SAC Consulting: Veterinary Services (SAC C VS).

PMID- 28450486
TI  - Adding a further twist to the tail of leptospirosis in the UK.

PMID- 28450488
TI  - Standardisation of dry cow therapy terminology.

PMID- 28450490
TI  - Optimising the value of VNs.

PMID- 28450489
TI  - Optimising the value of VNs.

PMID- 28450491
TI  - Mycobacterium microti infection in a cow in France.

PMID- 28450492
TI  - Mucosal disease in a group of persistently infected cattle.

PMID- 28450493
TI  - Pain in pet rabbits.

PMID- 28450494
TI  - Informed clients benefit practices and pets.
AB  - White Cross Vets in Derby recently opened its doors and invited local pet owners
      to come and learn about what to do - and what not to do - in a pet emergency.
      Clinic director, Helen Johnson, says that informing clients can help bond them to
      a practice.

PMID- 28450495
TI  - Ten-minute chat.
AB  - To mark its 50th anniversary, the British Cattle Veterinary Association (BCVA) is
      attempting to raise L50,000 for the charity Send A Cow. The association's
      president Andrew Cobner explains what the charity does and who's involved in the
      fundraising.

PMID- 28450496
TI  - Should doctors engage with counterterrorism?

PMID- 28450497
TI  - Integrating 3-omics data analyze rat lung tissue of COPD states and medical
      intervention by delineation of molecular and pathway alterations.
AB  - Chronic obstructive pulmonary disease (COPD) is a serious health problem.
      However, the molecular pathogenesis of COPD remains unknown. Here, we explored
      the molecular effects of cigarette smoke and bacterial infection in lung tissues
      of COPD rats. We also investigated therapeutic effects of aminophylline (APL) on
      the COPD rats and integrated transcriptome, proteome, and metabolome data for a
      global view of molecular mechanisms of COPD progression. Using molecular function
      and pathway analyses, the genes and proteins regulated in COPD and APL-treated
      rats were mainly attributed to oxidoreductase, antioxidant activity, energy and
      fatty acid metabolism. Furthermore, we identified hub proteins such as Gapdh
      (glyceraldehyde-3-phosphate dehydrogenase), Pkm (pyruvate kinase isozymes M1/M2),
      and Sod1 (superoxide dismutase 1), included in energy metabolism and oxidative
      stress. Then, we identified the significantly regulated metabolic pathways in
      lung tissues of COPD- and APL-treated rats, such as arachidonic acid, linoleic
      acid, and alpha-linolenic acid metabolism, which belong to the lipid metabolism.
      In particular, we picked the arachidonic acid metabolism for a more detailed
      pathway analysis of transcripts, proteins, and metabolites. We could observe an
      increase in metabolites and genes involved in arachidonic acid metabolism in COPD
      rats and the decrease in these in APL-treated rats, suggesting that inflammatory
      responses were up-regulated in COPD rats and down-regulated in APL-treated rats.
      In conclusion, these system-wide results suggested that COPD progression and its
      treatment might be associated with oxidative stress, lipid and energy metabolism
      disturbance. Additionally, we demonstrated the power of integrated omics for the
      elucidation of genes, proteins, and metabolites' changes and disorders that were
      associated with COPD.

PMID- 28450498
TI  - Robert Chapple.

PMID- 28450499
TI  - Draft Genome Sequence of Uncultured Upland Soil Cluster Gammaproteobacteria Gives
      Molecular Insights into High-Affinity Methanotrophy.
AB  - Aerated soils form the second largest sink for atmospheric CH4 A near-complete
      genome of uncultured upland soil cluster Gammaproteobacteria that oxidize CH4 at
      <2.5 ppmv was obtained from incubated Antarctic mineral cryosols. This first
      genome of high-affinity methanotrophs can help resolve the mysteries about their
      phylogenetic affiliation and metabolic potential.

PMID- 28450500
TI  - Draft Genome Sequence of Streptomyces sp. Strain IB2014011-1, Isolated from
      Trichoptera sp. Larvae of Lake Baikal.
AB  - Unique ecosystems with specific environmental conditions have been proven to be a
      promising source for isolation of new actinobacterial strains. Ancient Lake
      Baikal is one of the greatest examples of an ecosystem with high species
      biodiversity and endemicity caused by long-lasting isolated evolution and stable
      environmental conditions. Herein we report the draft genome sequence of
      Streptomyces sp. strain IB2014011-1, which was isolated from insect Trichoptera
      sp. larvae collected at the bottom of Lake Baikal.

PMID- 28450501
TI  - Draft Genome Sequence of NDM-1-Producing Leclercia adecarboxylata.
AB  - Here, we provide the first draft genome sequence of NDM-1-producing Leclercia
      adecarboxylata, a human-opportunistic pathogen. The draft genome sequence
      consists of a total length of 5.13 Mbp, with an average G+C content of 55.2%.

PMID- 28450502
TI  - Draft Genome Sequences of Salmonella enterica subsp. enterica Serovar Typhimurium
      Strains Isolated from Chicken and Swine Carcasses in Two Distinct Geographical
      Regions from Rio de Janeiro State, Brazil.
AB  - Salmonella enterica subsp. enterica serovar Typhimurium is a surveyed worldwide
      serotype with well-characterized genomes for several different strains. In
      Brazil, very few studies have submitted whole-genome sequences to GenBank. This
      genome may be useful to analyze the genetic mechanisms comparable to those of
      other related studies conducted in Brazil and globally.

PMID- 28450503
TI  - Draft Genome Sequence of the Potassium Feldspar-Solubilizing Bacterium Ensifer
      adhaerens L18.
AB  - Ensifer adhaerens L18, isolated from potassium feldspar mining area soil, was
      found to be capable of solubilizing K from an insoluble K-bearing mineral source.
      Here, we report the draft genome sequence and annotation of the feldspar
      solubilizing bacterium Ensifer adhaerens L18. These data provide the basis to
      investigate the relative impact of bacteria in feldspar solubilizing and the
      molecular mechanism of the potassium feldspar's dissolution.

PMID- 28450504
TI  - Complete Genome Sequence of the Gamma-Aminobutyric Acid-Producing Strain
      Streptococcus thermophilus APC151.
AB  - Here is presented the whole-genome sequence of Streptococcus thermophilus APC151,
      isolated from a marine fish. This bacterium produces gamma-aminobutyric acid
      (GABA) in high yields and is biotechnologically suitable to produce naturally
      GABA-enriched biofunctional yogurt. Its complete genome comprises 2,097 genes and
      1,839,134 nucleotides, with an average G+C content of 39.1%.

PMID- 28450505
TI  - Complete Coding Sequences of Two Dengue Virus Type 2 Strains Isolated from an
      Outbreak in Burkina Faso in 2016.
AB  - We report here the complete coding sequences of two strains of dengue virus type
      2, isolated in France from patients returning from Burkina Faso in November 2016.
      Both strains (cosmopolitan genotype) are almost identical (99.91% nucleotide
      identity) and closely related to a strain circulating in Burkina Faso in 1983.

PMID- 28450506
TI  - Draft Genome Sequence of the Nylon Oligomer-Degrading Bacterium Arthrobacter sp.
      Strain KI72.
AB  - We report here the 4.6-Mb genome sequence of a nylon oligomer-degrading
      bacterium, Arthrobacter sp. strain KI72. The draft genome sequence of strain KI72
      consists of 4,568,574 bp, with a G+C content of 63.47%, 4,372 coding sequences
      (CDSs), 54 tRNAs, and six rRNAs.

PMID- 28450507
TI  - Draft Genome Sequence of the Yeast Starmerella bacillaris (syn.,
      Candidazemplinina) FRI751 Isolated from Fermenting Must of Dried Raboso Grapes.
AB  - Starmerella bacillaris is an ascomycetous yeast commonly present in enological
      environments. Here, we report the first draft genome sequence of S. bacillaris
      FRI751, which will facilitate the study of the characteristics of this
      interesting enological yeast.

PMID- 28450508
TI  - Genome Sequence of a Goose Parvovirus Strain Isolated from an Ill Goose in China.
AB  - We report here the complete genome sequence of a goose parvovirus (GPV) strain,
      RC16, which was isolated from an ill goose in 2016 at Rongchang, Chongqing,
      China. The GPV strain RC16 isolated was passaged and identified, whose full
      length genome is 5,046 nucleotides long.

PMID- 28450509
TI  - Draft Genome Sequence of a Biodesulfurizing Bacterium, Gordonia sp. Strain
      IITR100.
AB  - We report here the whole-genome sequence of a biodesulfurizing bacterium,
      Gordonia sp. strain IITR100. The bacterium has the unique ability to desulfurize
      both aliphatic and aromatic organosulfurs. The draft genome sequence will provide
      insights into the various genes and regulators involved in biodesulfurization and
      other catabolic pathways.

PMID- 28450510
TI  - Complete Genome Sequences of Identical Zika virus Isolates in a Nursing Mother
      and Her Infant.
AB  - Complete genome sequences were obtained for Zika viruses isolated from the breast
      milk of a Venezuelan patient and her child, who was exclusively breastfeeding at
      the time. These sequences are the first to be reported from a presumptive
      autochthonous postnatal transmission case from mother to child in Venezuela.

PMID- 28450511
TI  - Complete Genome Sequence of Bordetella pertussis Pelita III, the Production
      Strain for an Indonesian Whole-Cell Pertussis Vaccine.
AB  - PT Bio Farma, the sole World Health Organization-approved Indonesian vaccine
      producer, manufactures a whole-cell whooping cough vaccine (wP) that, as part of
      a pentavalent diphtheria-tetanus-pertussis/hepatitis B/Haemophilus influenzae b
      (DTP/HB/Hib) vaccine, is used in Indonesia and many other countries. We report
      here the whole-genome sequence for Bordetella pertussis Pelita III, PT Bio
      Farma's wP production strain.

PMID- 28450512
TI  - Genome Sequence of "Candidatus Carsonella ruddii" Strain BC, a Nutritional
      Endosymbiont of Bactericera cockerelli.
AB  - Here, we report the genome of "Candidatus Carsonella ruddii" strain BC, a
      nutritional endosymbiont of the tomato psyllid Bactericera cockerelli The 173,802
      bp genome contains 198 protein-coding genes, with a G+C content of 14.8%.

PMID- 28450513
TI  - Complete Genome Sequence of Tessaracoccus sp. Strain T2.5-30 Isolated from 139.5
      Meters Deep on the Subsurface of the Iberian Pyritic Belt.
AB  - Here, we report the complete genome sequence of Tessaracoccus sp. strain T2.5-30,
      which consists of a chromosome with 3.2 Mbp, 70.4% G+C content, and 3,005 coding
      DNA sequences. The strain was isolated from a rock core retrieved at a depth of
      139.5 m in the subsurface of the Iberian Pyritic Belt (Spain).

PMID- 28450514
TI  - Draft Genome Sequence of MPKL 26, the Type Strain of the Novel Species Sinomonas
      mesophila.
AB  - Sinomonas mesophila MPKL 26T can produce silver nanoparticles. Here, we present
      the 4.0-Mb genome of this type strain, which contains 47 scaffolds with an N50
      scaffold length of 261,266 bp. The availability of the genome sequence will
      provide a better understanding of strain MPKL 26T and the genus Sinomonas.

PMID- 28450515
TI  - Draft Genome Sequence of Mycobacterium ulcerans S4018 Isolated from a Patient
      with an Active Buruli Ulcer in Benin, Africa.
AB  - Currently, there are only two publicly available genomes of Mycobacterium
      ulcerans-the causative agent of the neglected, but devastating, tropical disease
      Buruli ulcer. Here, we report the draft genome sequence of isolate S4018,
      recovered from an active cutaneous lesion of a patient with Buruli ulcer in
      Benin, Africa.

PMID- 28450516
TI  - Genome Sequence of a Providencia stuartii Strain Isolated from Luciliasericata
      Salivary Glands.
AB  - We present here the draft genome sequence of a Providencia stuartii strain,
      derived from the salivary glands of larval Lucilia sericata, a common blow fly
      important to forensic, medical, and veterinary science. The genome sequence will
      help dissect coinfections involving P. stuartii and Proteus mirabilis, as well as
      blow fly-bacteria interactions.

PMID- 28450517
TI  - Draft Genome Sequence of Microbacterium sp. TNHR37B Isolated from a Heated
      Aquifer Bore Well of the Great Artesian Basin, Australia.
AB  - Microbacterium sp. strain TNHR37B was isolated from a geothermal bore well sample
      (50 degrees C) collected from a region of coal seam gas extraction activities.
      The 3.5-Mb genome with a G+C content of 69.9% contained unique genes, and a low
      similarity value for average nucleotide identity using BLAST was observed with
      the available 73 Microbacterium sp. genomes.

PMID- 28450519
TI  - Draft Genome Sequence of Exiguobacterium sp. HVEsp1, a Thermophilic Bacterium
      Isolated from a Deep-Sea Hydrothermal Vent in the Okinawa Trough.
AB  - We report here the draft genome sequence of Exiguobacterium sp. HVEsp1, a
      thermophilic bacterium isolated from a deep-sea hydrothermal vent. The estimated
      genome size of this strain is 2,838,499 bp with a G+C content of 48.2%. The
      genome sequence data provide valuable information that will facilitate studies on
      the adaptation mechanisms of bacteria living in deep-sea hydrothermal vents.

PMID- 28450518
TI  - Complete Genome Sequence of a Paenalcaligenes hominis Strain Isolated from a
      Paraplegic Patient with Neurogenic Bladder Using Single-Molecule Real-Time
      Sequencing Technology.
AB  - The genome of Paenalcaligenes hominis, isolated from a paraplegic patient with
      neurogenic bladder, was sequenced with the Pacific Biosciences RSII platform. The
      genome size is 2.68 Mb and includes 3,096 annotated coding sequences, including
      genes associated with quinone cofactors, which play crucial roles in the
      virulence of Gram-negative bacteria.

PMID- 28450520
TI  - Draft Genome Sequence of the 1,2-Dichloroethane-Utilizing Micrococcus sp. Strain
      NDB3Y10, Isolated from an Australian Bore Well Producing Coal Seam Gas.
AB  - Micrococcus luteus strain NDB3Y10, which utilizes 1,2-dichloroethane as a carbon
      source, was isolated from a bore well that produces coal seam gas. The draft
      genome size of the strain was 2.49 Mb with a G+C content of 72.97%. Genes
      involved in the metabolism of halogenated substrates, including halogenated
      hydrocarbons, were identified.

PMID- 28450521
TI  - Complete Genome Sequence of a Bovine Viral Diarrhea Virus Subgenotype 1g Strain
      Isolated in Italy.
AB  - We report here the full-length sequence of the bovine viral diarrhea virus (BVDV)
      strain UM/103/04, isolated from a persistently infected cow in Italy. It belongs
      to the subgenotype 1g, which is described as a sporadic subgenotype in Italy.
      This is the first report of a complete genome sequence of BVDV-1g.

PMID- 28450522
TI  - Draft Genome Sequence of Bacillus respiratorii VT-16-64, Isolated from the
      Bronchiolar Alveolar Lavage Fluid of a Patient with Chronic Obstructive Pulmonary
      Disease.
AB  - We report here the draft genome sequence of Bacillus respiratorii VT-16-64, a
      novel spore-forming bacterium isolated from the bronchiolar alveolar lavage fluid
      of a patient with chronic obstructive pulmonary disease. The genome was comprised
      4,831,386 bp with 4,399 predicted protein-coding genes, including those
      associated with antibiotic resistance and virulence.

PMID- 28450523
TI  - Isolation of Two Virus-Like Circular DNAs from Commercially Available Milk
      Samples.
AB  - Epidemiological data indicate a potential relationship between milk and dairy
      product consumption and the incidence of breast cancer, as well as
      neurodegenerative diseases. We report the isolation of two novel circular DNA
      molecules isolated from commercially available milk.

PMID- 28450524
TI  - Draft Genome Sequence of Streptomyces scabrisporus NF3, an Endophyte Isolated
      from Amphipterygium adstringens.
AB  - We report the draft genome sequence of Streptomyces scabrisporus NF3, an
      endophyte isolated from Amphipterygium adstringens in Chiapas, Mexico. This
      strain produces a new modified linaridin peptide. The genome harbors at least 50
      gene clusters for synthases of polyketide and nonribosomal peptides, suggesting a
      prospective production of various secondary metabolites.

PMID- 28450525
TI  - Draft Genome Sequences of "Candidatus Synechococcus spongiarum," Cyanobacterial
      Symbionts of the Mediterranean Sponge Aplysina aerophoba.
AB  - We report here four draft genome sequences belonging to clade F of the
      cyanobacterium "Candidatus Synechococcus spongiarum" of the marine sponge
      Aplysina aerophoba, which were collected from two nearby locations in the
      northern Adriatic Sea. The sequences provide the basis for within-clade
      comparisons between members of this widespread group of cyanobacterial sponge
      symbionts.

PMID- 28450526
TI  - Draft Genome Sequence of Plantibacterflavus Strain 251 Isolated from a Plant
      Growing in a Chronically Hydrocarbon-Contaminated Site.
AB  - Plantibacter flavus isolate 251 is a bacterial endophyte isolated from an
      Achillea millefolium plant growing in a natural oil seep soil located in Oil
      Springs, Ontario, Canada. We present here a draft genome sequence of an
      infrequently reported genus Plantibacter, highlighting an endophytic lifestyle
      and biotechnological potential.

PMID- 28450527
TI  - Draft Genome Sequence of the Uropathogenic Herbaspirillumfrisingense Strain
      ureolyticus VT-16-41.
AB  - Herbaspirillum frisingense strain ureolyticus VT-16-41 is a clinical cystitis
      isolate. Here, we report the draft genome sequence of the uropathogenic H.
      frisingense strain ureolyticus VT-16-41, which contains various antibiotic
      resistance genes and virulence factors that enable it to colonize and persist in
      the urinary tract.

PMID- 28450528
TI  - Draft Genome Sequence of Rhizobiumpusense Strain NRCPB10T (LMG 25623T) Isolated
      from Rhizosphere Soil of Chickpeas (Cicer arietinum L.) Grown in India.
AB  - Rhizobium pusense strain NRCPB10T was isolated from rhizosphere soil of chickpeas
      (Cicer arietinum L.). Based upon the draft genome sequence, the genome is 5.28 Mb
      and encodes 5,064 proteins.

PMID- 28450530
TI  - Lessons from the lower airway microbiome in early CF.

PMID- 28450529
TI  - Identification and validation of distinct biological phenotypes in patients with
      acute respiratory distress syndrome by cluster analysis.
AB  - RATIONALE: We hypothesised that patients with acute respiratory distress syndrome
      (ARDS) can be clustered based on concentrations of plasma biomarkers and that the
      thereby identified biological phenotypes are associated with mortality. METHODS:
      Consecutive patients with ARDS were included in this prospective observational
      cohort study. Cluster analysis of 20 biomarkers of inflammation, coagulation and
      endothelial activation provided the phenotypes in a training cohort, not taking
      any outcome data into account. Logistic regression with backward selection was
      used to select the most predictive biomarkers, and these predicted phenotypes
      were validated in a separate cohort. Multivariable logistic regression was used
      to quantify the independent association with mortality. RESULTS: Two phenotypes
      were identified in 454 patients, which we named 'uninflamed' (N=218) and
      'reactive' (N=236). A selection of four biomarkers (interleukin-6, interferon
      gamma, angiopoietin 1/2 and plasminogen activator inhibitor-1) could be used to
      accurately predict the phenotype in the training cohort (area under the receiver
      operating characteristics curve: 0.98, 95% CI 0.97 to 0.99). Mortality rates were
      15.6% and 36.4% (p<0.001) in the training cohort and 13.6% and 37.5% (p<0.001) in
      the validation cohort (N=207). The 'reactive phenotype' was independent from
      confounders associated with intensive care unit mortality (training cohort: OR
      1.13, 95% CI 1.04 to 1.23; validation cohort: OR 1.18, 95% CI 1.06 to 1.31).
      CONCLUSIONS: Patients with ARDS can be clustered into two biological phenotypes,
      with different mortality rates. Four biomarkers can be used to predict the
      phenotype with high accuracy. The phenotypes were very similar to those found in
      cohorts derived from randomised controlled trials, and these results may improve
      patient selection for future clinical trials targeting host response in patients
      with ARDS.

PMID- 28450531
TI  - Thousands of RNA-cached copies of whole chromosomes are present in the ciliate
      Oxytricha during development.
AB  - The ciliate Oxytricha trifallax maintains two genomes: a germline genome that is
      active only during sexual conjugation and a transcriptionally active, somatic
      genome that derives from the germline via extensive sequence reduction and
      rearrangement. Previously, we found that long noncoding (lnc) RNA "templates"
      telomere-containing, RNA-cached copies of mature chromosomes-provide the
      information to program the rearrangement process. Here we used a modified RNA-seq
      approach to conduct the first genome-wide search for endogenous, telomere-to
      telomere RNA transcripts. We find that during development, Oxytricha produces
      long noncoding RNA copies for over 10,000 of its 16,000 somatic chromosomes,
      consistent with a model in which Oxytricha transmits an RNA-cached copy of its
      somatic genome to the sexual progeny. Both the primary sequence and expression
      profile of a somatic chromosome influence the temporal distribution and abundance
      of individual template RNAs. This suggests that Oxytricha may undergo multiple
      rounds of DNA rearrangement during development. These observations implicate a
      complex set of thousands of long RNA molecules in the wiring and maintenance of a
      highly elaborate somatic genome architecture.

PMID- 28450532
TI  - P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer.
AB  - miRNAs have emerged as key participants of p53 signaling pathways because they
      regulate or are regulated by p53. Here, we provide the first study demonstrating
      direct regulation of an oncogenic miRNA, miR-191-5p, by p53 and existence of a
      regulatory feedback loop. Using a combination of qRT-PCR, promoter-luciferase,
      and chromatin-immunoprecipitation assays, we show that p53 brings about down
      regulation of miR-191-5p in breast cancer. miR-191-5p overexpression brought
      about inhibition of apoptosis in breast cancer cell lines (MCF7 and ZR-75) as
      demonstrated by reduction in annexin-V stained cells and caspase 3/7 activity,
      whereas miR-191-5p down-regulation showed the opposite. We further unveiled that
      SOX4 was a direct target of miR-191-5p. SOX4 overexpression was shown to increase
      p53 protein levels in MCF7 cells. miR-191-5p overexpression brought about down
      regulation of SOX4 and thus p53 levels, suggesting the existence of a regulatory
      feedback loop. Breast cancer treatment by doxorubicin, an anti-cancer drug,
      involves induction of apoptosis by p53; we thus wanted to check whether miR-191
      5p affects doxorubicin sensitivity. Interestingly, Anti-miR-191 treatment
      significantly decreased the IC50 of the doxorubicin drug and thus sensitized
      breast cancer cells to doxorubicin treatment by promoting apoptosis. Overall,
      this work highlights the importance of the p53-miR-191-SOX4 axis in the
      regulation of apoptosis and drug resistance in breast cancer and offers a
      preclinical proof-of-concept for use of an Anti-miR-191 and doxorubicin
      combination as a rational approach to pursue for better breast cancer treatment.

PMID- 28450533
TI  - MCTBI: a web server for predicting metal ion effects in RNA structures.
AB  - Metal ions play critical roles in RNA structure and function. However, web
      servers and software packages for predicting ion effects in RNA structures are
      notably scarce. Furthermore, the existing web servers and software packages
      mainly neglect ion correlation and fluctuation effects, which are potentially
      important for RNAs. We here report a new web server, the MCTBI server
      (http://rna.physics.missouri.edu/MCTBI), for the prediction of ion effects for
      RNA structures. This server is based on the recently developed MCTBI, a model
      that can account for ion correlation and fluctuation effects for nucleic acid
      structures and can provide improved predictions for the effects of metal ions,
      especially for multivalent ions such as Mg2+ effects, as shown by extensive
      theory-experiment test results. The MCTBI web server predicts metal ion binding
      fractions, the most probable bound ion distribution, the electrostatic free
      energy of the system, and the free energy components. The results provide
      mechanistic insights into the role of metal ions in RNA structure formation and
      folding stability, which is important for understanding RNA functions and the
      rational design of RNA structures.

PMID- 28450534
TI  - Quantifying Postdonation Risk of ESRD in Living Kidney Donors.
AB  - Studies have estimated the average risk of postdonation ESRD for living kidney
      donors in the United States, but personalized estimation on the basis of donor
      characteristics remains unavailable. We studied 133,824 living kidney donors from
      1987 to 2015, as reported to the Organ Procurement and Transplantation Network,
      with ESRD ascertainment via Centers for Medicare and Medicaid Services linkage,
      using Cox regression with late entries. Black race (hazard ratio [HR], 2.96; 95%
      confidence interval [95% CI], 2.25 to 3.89; P<0.001) and male sex (HR, 1.88; 95%
      CI, 1.50 to 2.35; P<0.001) was associated with higher risk of ESRD in donors.
      Among nonblack donors, older age was associated with greater risk (HR per 10
      years, 1.40; 95% CI, 1.23 to 1.59; P<0.001). Among black donors, older age was
      not significantly associated with risk (HR, 0.88; 95% CI, 0.72 to 1.09; P=0.3).
      Greater body mass index was associated with higher risk (HR per 5 kg/m2, 1.61;
      95% CI, 1.29 to 2.00; P<0.001). Donors who had a first-degree biological
      relationship to the recipient had increased risk (HR, 1.70; 95% CI, 1.24 to 2.34;
      P<0.01). C-statistic of the model was 0.71. Predicted 20-year risk of ESRD for
      the median donor was only 34 cases per 10,000 donors, but 1% of donors had
      predicted risk exceeding 256 cases per 10,000 donors. Risk estimation is critical
      for appropriate informed consent and varies substantially across living kidney
      donors. Greater permissiveness may be warranted in older black candidate donors;
      young black candidates should be evaluated carefully.

PMID- 28450535
TI  - Sodium Channel Nav1.8 Underlies TTX-Resistant Axonal Action Potential Conduction
      in Somatosensory C-Fibers of Distal Cutaneous Nerves.
AB  - Voltage-gated sodium (NaV) channels are responsible for the initiation and
      conduction of action potentials within primary afferents. The nine NaV channel
      isoforms recognized in mammals are often functionally divided into tetrodotoxin
      (TTX)-sensitive (TTX-s) channels (NaV1.1-NaV1.4, NaV1.6-NaV1.7) that are blocked
      by nanomolar concentrations and TTX-resistant (TTX-r) channels (NaV1.8 and
      NaV1.9) inhibited by millimolar concentrations, with NaV1.5 having an
      intermediate toxin sensitivity. For small-diameter primary afferent neurons, it
      is unclear to what extent different NaV channel isoforms are distributed along
      the peripheral and central branches of their bifurcated axons. To determine the
      relative contribution of TTX-s and TTX-r channels to action potential conduction
      in different axonal compartments, we investigated the effects of TTX on C-fiber
      mediated compound action potentials (C-CAPs) of proximal and distal peripheral
      nerve segments and dorsal roots from mice and pigtail monkeys (Macaca
      nemestrina). In the dorsal roots and proximal peripheral nerves of mice and
      nonhuman primates, TTX reduced the C-CAP amplitude to 16% of the baseline. In
      contrast, >30% of the C-CAP was resistant to TTX in distal peripheral branches of
      monkeys and WT and NaV1.9-/- mice. In nerves from NaV1.8-/- mice, TTX-r C-CAPs
      could not be detected. These data indicate that NaV1.8 is the primary isoform
      underlying TTX-r conduction in distal axons of somatosensory C-fibers.
      Furthermore, there is a differential spatial distribution of NaV1.8 within C
      fiber axons, being functionally more prominent in the most distal axons and
      terminal regions. The enrichment of NaV1.8 in distal axons may provide a useful
      target in the treatment of pain of peripheral origin.SIGNIFICANCE STATEMENT It is
      unclear whether individual sodium channel isoforms exert differential roles in
      action potential conduction along the axonal membrane of nociceptive,
      unmyelinated peripheral nerve fibers, but clarifying the role of sodium channel
      subtypes in different axonal segments may be useful for the development of novel
      analgesic strategies. Here, we provide evidence from mice and nonhuman primates
      that a substantial portion of the C-fiber compound action potential in distal
      peripheral nerves, but not proximal nerves or dorsal roots, is resistant to
      tetrodotoxin and that, in mice, this effect is mediated solely by voltage-gated
      sodium channel 1.8 (NaV1.8). The functional prominence of NaV1.8 within the
      axonal compartment immediately proximal to its termination may affect strategies
      targeting pain of peripheral origin.

PMID- 28450536
TI  - Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold
      Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.
AB  - Backpropagating action potentials (bAPs) are indispensable in dendritic
      signaling. Conflicting Ca2+-imaging data and an absence of dendritic recording
      data means that the extent of backpropagation in thalamocortical (TC) and
      thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons
      signal electrically through dendrodendritic gap junctions and possibly via
      chemical dendritic GABAergic synapses, as well as classical axonal GABA release,
      this lack of knowledge is problematic. To address this issue, we made two-photon
      targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure
      bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike
      (LTS) "burst" APs in both cell types are always recorded first at the soma before
      backpropagating into the dendrites while undergoing substantial distance
      dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation
      strength varies according to firing mode. During LTS bursts, somatic AP half
      width increases progressively with increasing spike number, allowing late-burst
      spikes to propagate more efficiently into the dendritic tree compared with spikes
      occurring at burst onset. Tonic spikes have similar somatic half-widths to late
      burst spikes and undergo similar dendritic attenuation. In contrast, in TRN
      neurons, AP properties are unchanged between LTS bursts and tonic firing and, as
      a result, distance-dependent dendritic attenuation remains consistent across
      different firing modes. Therefore, unlike LTS-associated global electrical and
      calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is
      more restricted, with potentially important behavioral-state-dependent
      consequences for synaptic integration and plasticity in thalamic
      neurons.SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate
      in the axosomatic region and propagate into the dendritic tree to provide a
      retrograde signal that conveys information about the level of cellular output to
      the locations that receive most input: the dendrites. In thalamocortical and
      thalamic reticular nucleus neurons, the site of AP generation and the true extent
      of backpropagation remain unknown. Using patch-clamp recordings, this study
      measures dendritic propagation of APs directly in these neurons. In either cell
      type, high-frequency low-threshold spike burst or lower-frequency tonic APs
      undergo substantial voltage attenuation as they spread into the dendritic tree.
      Therefore, backpropagating spikes in these cells can only influence signaling in
      the proximal part of the dendritic tree.

PMID- 28450537
TI  - Being First Matters: Topographical Representational Similarity Analysis of ERP
      Signals Reveals Separate Networks for Audiovisual Temporal Binding Depending on
      the Leading Sense.
AB  - In multisensory integration, processing in one sensory modality is enhanced by
      complementary information from other modalities. Intersensory timing is crucial
      in this process because only inputs reaching the brain within a restricted
      temporal window are perceptually bound. Previous research in the audiovisual
      field has investigated various features of the temporal binding window, revealing
      asymmetries in its size and plasticity depending on the leading input: auditory
      visual (AV) or visual-auditory (VA). Here, we tested whether separate neuronal
      mechanisms underlie this AV-VA dichotomy in humans. We recorded high-density EEG
      while participants performed an audiovisual simultaneity judgment task including
      various AV-VA asynchronies and unisensory control conditions (visual-only,
      auditory-only) and tested whether AV and VA processing generate different
      patterns of brain activity. After isolating the multisensory components of AV-VA
      event-related potentials (ERPs) from the sum of their unisensory constituents, we
      ran a time-resolved topographical representational similarity analysis (tRSA)
      comparing the AV and VA ERP maps. Spatial cross-correlation matrices were built
      from real data to index the similarity between the AV and VA maps at each time
      point (500 ms window after stimulus) and then correlated with two alternative
      similarity model matrices: AVmaps = VAmaps versus AVmaps ? VAmaps The tRSA
      results favored the AVmaps ? VAmaps model across all time points, suggesting that
      audiovisual temporal binding (indexed by synchrony perception) engages different
      neural pathways depending on the leading sense. The existence of such dual route
      supports recent theoretical accounts proposing that multiple binding mechanisms
      are implemented in the brain to accommodate different information parsing
      strategies in auditory and visual sensory systems.SIGNIFICANCE STATEMENT
      Intersensory timing is a crucial aspect of multisensory integration, determining
      whether and how inputs in one modality enhance stimulus processing in another
      modality. Our research demonstrates that evaluating synchrony of auditory-leading
      (AV) versus visual-leading (VA) audiovisual stimulus pairs is characterized by
      two distinct patterns of brain activity. This suggests that audiovisual
      integration is not a unitary process and that different binding mechanisms are
      recruited in the brain based on the leading sense. These mechanisms may be
      relevant for supporting different classes of multisensory operations, for
      example, auditory enhancement of visual attention (AV) and visual enhancement of
      auditory speech (VA).

PMID- 28450538
TI  - Modulation of Illusory Reversal in Tactile Temporal Order by the Phase of
      Posterior alpha Rhythm.
AB  - The subjective temporal order of tactile stimuli, delivered sequentially to each
      hand with an interval of 100-300 ms, is often inverted when the arms are crossed.
      Based on data from behavioral and neuroimaging studies, it has been proposed that
      the reversal is due to a conflict between anatomical and spatial representations
      of the tactile signal or to the production of an inverted apparent motion signal.
      Because the alpha rhythms, which consist of a few distinct components, reportedly
      modulate tactile perception and apparent motion and serve as a 10 Hz timer, we
      hypothesized that the illusory reversal would be regulated by some of the alpha
      rhythms. To test this hypothesis, we conducted magnetoencephalographic recordings
      in both male and female participants during the tactile temporal order judgment
      task. We decomposed the alpha rhythms into five independent components and
      discovered that the illusory reversal was modulated by the phase of one
      independent component with strong current sources near the parieto-occipital (PO)
      sulcus (peri-PO component). As expected, the estimated current sources
      distributed over the human MST implicated to represent tactile apparent motion,
      in addition to the intraparietal region implicated in mapping tactile signals in
      space. However, the strongest source was located in the precuneus that occupies a
      central hub region in the cortical networks and receives tactile inputs through a
      tecto-thalamic pathway. These results suggest that the peri-PO component plays an
      essential role in regulating tactile temporal perception by modulating the
      thalamic nuclei that interconnect the superior colliculus with the cortical
      networks.SIGNIFICANCE STATEMENT Despite a long-held hypothesis that the posterior
      alpha rhythm serves as a 10 Hz timer that regulates human temporal perception,
      the contribution of the alpha rhythms in temporal perception is still unclear. We
      examined how the alpha rhythms influence tactile temporal order judgment.
      Judgment reversal depended on the phase of one particular alpha rhythm with its
      source near the parieto-occipital sulcus. The peri-parieto-occipital alpha rhythm
      may play a crucial role in organizing tactile temporal perception.

PMID- 28450539
TI  - Multisensory Integration Uses a Real-Time Unisensory-Multisensory Transform.
AB  - The manner in which the brain integrates different sensory inputs to facilitate
      perception and behavior has been the subject of numerous speculations. By
      examining multisensory neurons in cat superior colliculus, the present study
      demonstrated that two operational principles are sufficient to understand how
      this remarkable result is achieved: (1) unisensory signals are integrated
      continuously and in real time as soon as they arrive at their common target
      neuron and (2) the resultant multisensory computation is modified in shape and
      timing by a delayed, calibrating inhibition. These principles were tested for
      descriptive sufficiency by embedding them in a neurocomputational model and using
      it to predict a neuron's moment-by-moment multisensory response given only
      knowledge of its responses to the individual modality-specific component cues.
      The predictions proved to be highly accurate, reliable, and unbiased and were, in
      most cases, not statistically distinguishable from the neuron's actual
      instantaneous multisensory response at any phase throughout its entire duration.
      The model was also able to explain why different multisensory products are often
      observed in different neurons at different time points, as well as the higher
      order properties of multisensory integration, such as the dependency of
      multisensory products on the temporal alignment of crossmodal cues. These
      observations not only reveal this fundamental integrative operation, but also
      identify quantitatively the multisensory transform used by each neuron. As a
      result, they provide a means of comparing the integrative profiles among neurons
      and evaluating how they are affected by changes in intrinsic or extrinsic
      factors.SIGNIFICANCE STATEMENT Multisensory integration is the process by which
      the brain combines information from multiple sensory sources (e.g., vision and
      audition) to maximize an organism's ability to identify and respond to
      environmental stimuli. The actual transformative process by which the neural
      products of multisensory integration are achieved is poorly understood. By
      focusing on the millisecond-by-millisecond differences between a neuron's
      unisensory component responses and its integrated multisensory response, it was
      found that this multisensory transform can be described by two basic principles:
      unisensory information is integrated in real time and the multisensory response
      is shaped by calibrating inhibition. It is now possible to use these principles
      to predict a neuron's multisensory response accurately armed only with knowledge
      of its unisensory responses.

PMID- 28450540
TI  - APLP1 Is a Synaptic Cell Adhesion Molecule, Supporting Maintenance of Dendritic
      Spines and Basal Synaptic Transmission.
AB  - The amyloid precursor protein (APP), a key player in Alzheimer's disease, belongs
      to the family of synaptic adhesion molecules (SAMs) due to its impact on synapse
      formation and synaptic plasticity. These functions are mediated by both the
      secreted APP ectodomain that acts as a neurotrophic factor and full-length APP
      forming trans-cellular dimers. Two homologs of APP exist in mammals: the APP like
      proteins APLP1 and APLP2, exhibiting functions that partly overlap with those of
      APP. Here we tested whether APLP1 and APLP2 also show features of SAMs. We found
      that all three family members were upregulated during postnatal development
      coinciding with synaptogenesis. We observed presynaptic and postsynaptic
      localization of all APP family members and could show that heterologous
      expression of APLP1 or APLP2 in non-neuronal cells induces presynaptic
      differentiation in contacting axons of cocultured neurons, similar to APP and
      other SAMs. Moreover, APP/APLPs all bind to synaptic-signaling molecules, such as
      MINT/X11. Furthermore, we report that aged APLP1 knock-out mice show impaired
      basal transmission and a reduced mEPSC frequency, likely resulting from reduced
      spine density. This demonstrates an essential nonredundant function of APLP1 at
      the synapse. Compared to APP, APLP1 exhibits increased trans-cellular binding and
      elevated cell-surface levels due to reduced endocytosis. In conclusion, our
      results establish that APLPs show typical features of SAMs and indicate that
      increased surface expression, as observed for APLP1, is essential for proper
      synapse formation in vitro and synapse maintenance in vivoSIGNIFICANCE STATEMENT
      According to the amyloid-cascade hypothesis, Alzheimer's disease is caused by the
      accumulation of Abeta peptides derived from sequential cleavage of the amyloid
      precursor protein (APP) by beta-site APP cleaving enzyme 1 (BACE1) and gamma
      secretase. Here we show that all mammalian APP family members (APP, APLP1, and
      APLP2) exhibit synaptogenic activity, involving trans-synaptic dimerization,
      similar to other synaptic cell adhesion molecules, such as Neuroligin/Neurexin.
      Importantly, our study revealed that the loss of APLP1, which is one of the major
      substrates of BACE1, causes reduced spine density in aged mice. Because some
      therapeutic interventions target APP processing (e.g., BACE inhibitors), those
      strategies may alter APP/APLP physiological function. This should be taken into
      account for the development of pharmaceutical treatments of Alzheimer's disease.

PMID- 28450541
TI  - Spatial Attention, Motor Intention, and Bayesian Cue Predictability in the Human
      Brain.
AB  - Predictions about upcoming events influence how we perceive and respond to our
      environment. There is increasing evidence that predictions may be generated based
      upon previous observations following Bayesian principles, but little is known
      about the underlying cortical mechanisms and their specificity for different
      cognitive subsystems. The present study aimed at identifying common and distinct
      neural signatures of predictive processing in the spatial attentional and motor
      intentional system. Twenty-three female and male healthy human volunteers
      performed two probabilistic cueing tasks with either spatial or motor cues while
      lying in the fMRI scanner. In these tasks, the percentage of cue validity changed
      unpredictably over time. Trialwise estimates of cue predictability were derived
      from a Bayesian observer model of behavioral responses. These estimates were
      included as parametric regressors for analyzing the BOLD time series. Parametric
      effects of cue predictability in valid and invalid trials were considered to
      reflect belief updating by precision-weighted prediction errors. The brain areas
      exhibiting predictability-dependent effects dissociated between the spatial
      attention and motor intention task, with the right temporoparietal cortex being
      involved during spatial attention and the left angular gyrus and anterior
      cingulate cortex during motor intention. Connectivity analyses revealed that all
      three areas showed predictability-dependent coupling with the right hippocampus.
      These results suggest that precision-weighted prediction errors of stimulus
      locations and motor responses are encoded in distinct brain regions, but that
      crosstalk with the hippocampus may be necessary to integrate new trialwise
      outcomes in both cognitive systems.SIGNIFICANCE STATEMENT The brain is able to
      infer the environments' statistical structure and responds strongly to expectancy
      violations. In the spatial attentional domain, it has been shown that parts of
      the attentional networks are sensitive to the predictability of stimuli. It
      remains unknown, however, whether these effects are ubiquitous or if they are
      specific for different cognitive systems. The present study compared the
      influence of model-derived cue predictability on brain activity in the spatial
      attentional and motor intentional system. We identified areas with distinct
      predictability-dependent activation for spatial attention and motor intention,
      but also common connectivity changes of these regions with the hippocampus. These
      findings provide novel insights into the generality and specificity of predictive
      processing signatures in the human brain.

PMID- 28450542
TI  - Neuronal Chloride Regulation via KCC2 Is Modulated through a GABAB Receptor
      Protein Complex.
AB  - GABAB receptors are G-protein-coupled receptors that mediate inhibitory synaptic
      actions through a series of downstream target proteins. It is increasingly
      appreciated that the GABAB receptor forms part of larger signaling complexes,
      which enable the receptor to mediate multiple different effects within neurons.
      Here we report that GABAB receptors can physically associate with the potassium
      chloride cotransporter protein, KCC2, which sets the driving force for the
      chloride-permeable ionotropic GABAA receptor in mature neurons. Using
      biochemical, molecular, and functional studies in rodent hippocampus, we show
      that activation of GABAB receptors results in a decrease in KCC2 function, which
      is associated with a reduction in the protein at the cell surface. These findings
      reveal a novel "crosstalk" between the GABA receptor systems, which can be
      recruited under conditions of high GABA release and which could be important for
      the regulation of inhibitory synaptic transmission.SIGNIFICANCE STATEMENT
      Synaptic inhibition in the brain is mediated by ionotropic GABAA receptors
      (GABAARs) and metabotropic GABAB receptors (GABABRs). To fully appreciate the
      function and regulation of these neurotransmitter receptors, we must understand
      their interactions with other proteins. We describe a novel association between
      the GABABR and the potassium-chloride cotransporter protein, KCC2. This
      association is significant because KCC2 sets the intracellular chloride
      concentration found in mature neurons and thereby establishes the driving force
      for the chloride-permeable GABAAR. We demonstrate that GABABR activation can
      regulate KCC2 at the cell surface in a manner that alters intracellular chloride
      and the reversal potential for the GABAAR. Our data therefore support an
      additional mechanism by which GABABRs are able to modulate fast synaptic
      inhibition.

PMID- 28450543
TI  - The Human Thalamus Is an Integrative Hub for Functional Brain Networks.
AB  - The thalamus is globally connected with distributed cortical regions, yet the
      functional significance of this extensive thalamocortical connectivity remains
      largely unknown. By performing graph-theoretic analyses on thalamocortical
      functional connectivity data collected from human participants, we found that
      most thalamic subdivisions display network properties that are capable of
      integrating multimodal information across diverse cortical functional networks.
      From a meta-analysis of a large dataset of functional brain-imaging experiments,
      we further found that the thalamus is involved in multiple cognitive functions.
      Finally, we found that focal thalamic lesions in humans have widespread distal
      effects, disrupting the modular organization of cortical functional networks.
      This converging evidence suggests that the human thalamus is a critical hub
      region that could integrate diverse information being processed throughout the
      cerebral cortex as well as maintain the modular structure of cortical functional
      networks.SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive
      relay station of information from sensory organs or subcortical structures to the
      cortex. However, the thalamus has extensive connections with the entire cerebral
      cortex, which can also serve to integrate information processing between cortical
      regions. In this study, we demonstrate that multiple thalamic subdivisions
      display network properties that are capable of integrating information across
      multiple functional brain networks. Moreover, the thalamus is engaged by tasks
      requiring multiple cognitive functions. These findings support the idea that the
      thalamus is involved in integrating information across cortical networks.

PMID- 28450544
TI  - Privileged Functional Connectivity between the Visual Word Form Area and the
      Language System.
AB  - The visual word form area (VWFA) is a region in the left occipitotemporal sulcus
      of literate individuals that is purportedly specialized for visual word
      recognition. However, there is considerable controversy about its functional
      specificity and connectivity, with some arguing that it serves as a domain
      general, rather than word-specific, visual processor. The VWFA is a critical
      region for testing hypotheses about the nature of cortical organization, because
      it is known to develop only through experience (i.e., reading acquisition), and
      widespread literacy is too recent to have influenced genetic determinants of
      brain organization. Using a combination of advanced fMRI analysis techniques,
      including individual functional localization, multivoxel pattern analysis, and
      high-resolution resting-state functional connectivity (RSFC) analyses, with data
      from 33 healthy adult human participants, we demonstrate that (1) the VWFA can
      discriminate words from nonword letter strings (pseudowords); (2) the VWFA has
      preferential RSFC with Wernicke's area and other core regions of the language
      system; and (3) the strength of the RSFC between the VWFA and Wernicke's area
      predicts performance on a semantic classification task with words but not other
      categories of visual stimuli. Our results are consistent with the hypothesis that
      the VWFA is specialized for lexical processing of real words because of its
      functional connectivity with Wernicke's area.SIGNIFICANCE STATEMENT The visual
      word form area (VWFA) is critical for determining the nature of category-related
      organization of the ventral visual system. However, its functional specificity
      and connectivity are fiercely debated. Recent work concluded that the VWFA is a
      domain-general, rather than word-specific, visual processor with no preferential
      functional connectivity with the language system. Using more advanced techniques,
      our results stand in stark contrast to these earlier findings. We demonstrate
      that the VWFA is highly specialized for lexical processing of real words, and
      that a fundamental factor driving this specialization is its preferential
      intrinsic functional connectivity with core regions of the language system. Our
      results support the hypothesis that intrinsic functional connectivity contributes
      to category-related specialization within the human ventral visual system.

PMID- 28450546
TI  - Nicotinic alpha4beta2 Cholinergic Receptor Influences on Dorsolateral Prefrontal
      Cortical Neuronal Firing during a Working Memory Task.
AB  - The primate dorsolateral prefrontal cortex (dlPFC) subserves top-down regulation
      of attention and working memory abilities. Depletion studies show that the
      neuromodulator acetylcholine (ACh) is essential to dlPFC working memory
      functions, but the receptor and cellular bases for cholinergic actions are just
      beginning to be understood. The current study found that nicotinic receptors
      comprised of alpha4 and beta2 subunits (alpha4beta2-nAChR) enhance the task
      related firing of delay and fixation cells in the dlPFC of monkeys performing a
      working memory task. Iontophoresis of alpha4beta2-nAChR agonists increased the
      neuronal firing and enhanced the spatial tuning of delay cells, neurons that
      represent visual space in the absence of sensory stimulation. These enhancing
      effects were reversed by coapplication of a alpha4beta2-nAChR antagonist,
      consistent with actions at alpha4beta2-nAChR. Delay cell firing was reduced when
      distractors were presented during the delay epoch, whereas stimulation of
      alpha4beta2-nAChR protected delay cells from these deleterious effects.
      Iontophoresis of alpha4beta2-nAChR agonists also enhanced the firing of fixation
      cells, neurons that increase firing when the monkey initiates a trial, and
      maintain firing until the trial is completed. These neurons are thought to
      contribute to sustained attention and top-down motor control and have never
      before been the subject of pharmacological inquiry. These findings begin to build
      a picture of the cellular actions underlying the beneficial effects of ACh on
      attention and working memory. The data may also help to explain why genetic
      insults to alpha4 subunits are associated with working memory and attentional
      deficits and why alpha4beta2-nAChR agonists may have therapeutic
      potential.SIGNIFICANCE STATEMENT The acetylcholine (ACh) arousal system in the
      brain is needed for robust attention and working memory functions, but the
      receptor and cellular bases for its beneficial effects are poorly understood in
      the newly evolved primate brain. The current study found that ACh stimulation of
      nicotinic receptors comprised of alpha4 and beta2 subunits (alpha4beta2-nAChR)
      enhanced the firing of neurons in the primate prefrontal cortex that subserve top
      down attentional control and working memory. alpha4beta2-nAChR stimulation also
      protected neuronal responding from the detrimental effects of distracters
      presented during the delay epoch, when information is held in working memory.
      These results illuminate how ACh strengthens higher cognition and help to explain
      why genetic insults to the alpha4 subunit weaken cognitive and attentional
      abilities.

PMID- 28450545
TI  - Decreased Motor Neuron Support by SMA Astrocytes due to Diminished MCP1
      Secretion.
AB  - Spinal muscular atrophy (SMA) is an autosomal-recessive disorder characterized by
      severe, often fatal muscle weakness due to loss of motor neurons. SMA patients
      have deletions and other mutations of the survival of motor neuron 1 (SMN1) gene,
      resulting in decreased SMN protein. Astrocytes are the primary support cells of
      the CNS and are responsible for glutamate clearance, metabolic support, response
      to injury, and regulation of signal transmission. Astrocytes have been implicated
      in SMA as in in other neurodegenerative disorders. Astrocyte-specific rescue of
      SMN protein levels has been shown to mitigate disease manifestations in mice.
      However, the mechanism by which SMN deficiency in astrocytes may contribute to
      SMA is unclear and what aspect of astrocyte activity is lacking is unknown.
      Therefore, it is worthwhile to identify defects in SMN-deficient astrocytes that
      compromise normal function. We show here that SMA astrocyte cultures derived from
      mouse spinal cord of both sexes are deficient in supporting both WT and SMN
      deficient motor neurons derived from male, female, and mixed-sex sources and that
      this deficiency may be mitigated with secreted factors. In particular, SMN
      deficient astrocytes have decreased levels of monocyte chemoactive protein 1
      (MCP1) secretion compared with controls and MCP1 restoration stimulates outgrowth
      of neurites from cultured motor neurons. Correction of MCP1 deficiency may thus
      be a new therapeutic approach to SMA.SIGNIFICANCE STATEMENT Spinal muscular
      atrophy (SMA) is caused by the loss of motor neurons, but astrocyte dysfunction
      also contributes to the disease in mouse models. Monocyte chemoactive protein 1
      (MCP1) has been shown to be neuroprotective and is released by astrocytes. Here,
      we report that MCP1 levels are decreased in SMA mice and that replacement of
      deficient MCP1 increases differentiation and neurite length of WT and SMN
      deficient motor-neuron-like cells in cell culture. This study reveals a novel
      aspect of astrocyte dysfunction in SMA and indicates a possible approach for
      improving motor neuron growth and survival in this disease.

PMID- 28450547
TI  - Impaired popliteal artery flow-mediated dilation caused by reduced daily physical
      activity is prevented by increased shear stress.
AB  - We recently showed that 5 days of reduced daily physical activity impair
      popliteal artery, but not brachial artery, flow-mediated dilation (FMD). However,
      the mechanisms by which physical inactivity causes leg vascular dysfunction are
      unclear. We reason that a reduction in leg blood flow-induced shear stress is a
      primary underlying mechanism by which reduced daily physical activity impairs
      popliteal artery FMD. Thus the purpose of this study was to determine whether
      increased leg blood flow and shear stress during inactivity prevent the reduction
      in popliteal artery FMD. Bilateral popliteal artery FMD measures were performed
      at baseline and after 5 days of a transition from high (>10,000 steps/day) to low
      levels (<5,000 steps/day) of physical activity in 13 healthy and physically
      active men [20 +/- 2 (SD) yr]. During the inactive period, one foot was submerged
      in ~42 degrees C water (i.e., heated leg) three times a day for 30 min each
      period, to increase blood flow and thus shear stress, whereas the contralateral
      leg remained dry and served as internal control (i.e., nonheated leg). During
      heating, popliteal artery mean shear rate was increased in the heated leg (change
      of 119.3 +/- 26.4%, P < 0.01) but slightly decreased in the nonheated leg (change
      of -21.8 +/- 7.5%, P = 0.03). Popliteal artery FMD was impaired after 5 days of
      reduced daily physical activity in the control nonheated leg (P < 0.01) but was
      unchanged in the heated leg (P = 0.34). These results support the hypothesis that
      reduced leg blood flow-induced shear stress during physical inactivity is a key
      underlying mechanism mediating leg vascular dysfunction.NEW & NOTEWORTHY We found
      that the impairment in popliteal artery flow-mediated dilation caused by physical
      inactivity can be prevented by increased shear stress. These findings indicate
      that reduced leg blood flow-induced shear stress during physical inactivity may
      be a key underlying mechanism mediating the detrimental leg vascular effects of
      physical inactivity. Heating the foot area may be used as a nonpharmacological
      therapy to combat inactivity-induced leg vascular dysfunction, especially in
      people who are unable or unwilling to be active.

PMID- 28450548
TI  - Evidence for age-dependent air-space enlargement contributing to loss of lung
      tissue elastic recoil pressure and increased shear modulus in older age.
AB  - As a normal part of mature aging, lung tissue undergoes microstructural changes
      such as alveolar air-space enlargement and redistribution of collagen and elastin
      away from the alveolar duct. The older lung also experiences an associated
      decrease in elastic recoil pressure and an increase in specific tissue elastic
      moduli, but how this relates mechanistically to microstructural remodeling is not
      well-understood. In this study, we use a structure-based mechanics analysis to
      elucidate the contributions of age-related air-space enlargement and
      redistribution of elastin and collagen to loss of lung elastic recoil pressure
      and increase in tissue elastic moduli. Our results show that age-related
      geometric changes can result in reduction of elastic recoil pressure and increase
      in shear and bulk moduli, which is consistent with published experimental data.
      All elastic moduli were sensitive to the distribution of stiffness (representing
      elastic fiber density) in the alveolar wall, with homogenous stiffness near the
      duct and through the septae resulting in a more compliant tissue. The
      preferential distribution of elastic proteins around the alveolar duct in the
      healthy young adult lung therefore provides for a more elastic tissue.NEW &
      NOTEWORTHY We use a structure-based mechanics analysis to correlate air-space
      enlargement and redistribution of elastin and collagen to age-related changes in
      the mechanical behavior of lung parenchyma. Our study highlights that both the
      cause (redistribution of elastin and collagen) and the structural effect
      (alveolar air-space enlargement) contribute to decline in lung tissue elastic
      recoil with age; these results are consistent with published data and provide a
      new avenue for understanding the mechanics of the older lung.

PMID- 28450550
TI  - Biomechanical impact of provisional stenting and balloon dilatation on coronary
      bifurcation: clinical implications.
AB  - In-stent restenosis (ISR) and stent thrombosis remain clinically significant
      problems for bifurcations. Although the role of wall shear stress (WSS) has been
      well investigated, the role of circumferential wall stresses (CWS) has not been
      well studied in provisional stenting with and without final kissing balloon
      (FKB). We hypothesized that the perturbation of CWS at the SB in provisional
      stenting and balloon dilatation is an important factor in addition to WSS, and,
      hence, may affect restenosis rates (i.e., higher CWS correlates with higher
      restenosis). To test this hypothesis, we developed computational models of stent,
      FKB at bifurcation, and finite element simulations that considered both fluid and
      solid mechanics of the vessel wall. We computed the stress ratio (CWS/WSS) to
      show potential correlation with restenosis in clinical studies (i.e., higher
      stress ratio correlates with higher restenosis). Our simulation results show that
      stenting in the main branch (MB) increases the maximum CWS in the side branch
      (SB) and, hence, yields a higher stress ratio in the SB, as compared with the MB.
      FKB dilatation decreases the CWS and increases WSS, which collectively lowers the
      stress ratio in the SB. The changes of stress ratio were correlated positively
      with clinical data in provisional stenting and FKB. Both fluid and solid
      mechanics need to be evaluated when considering various stenting techniques at
      bifurcations, as solid stresses also play an important role in clinical outcome.
      An integrative index of bifurcation mechanics is the stress ratio that considers
      both CWS and WSS.NEW & NOTEWORTHY Although the role of wall shear stress (WSS)
      has been well investigated, the role of circumferential wall stresses (CWS) has
      not been well studied in provisional stenting with and without final kissing
      balloon. Both fluid and solid mechanics need to be evaluated when considering
      various stenting techniques at bifurcations. An integrative index of bifurcation
      mechanics is the stress ratio that considers both CWS and WSS.

PMID- 28450549
TI  - Effect of acute physiological free fatty acid elevation in the context of
      hyperinsulinemia on fiber type-specific IMCL accumulation.
AB  - It is well described that increasing free fatty acids (FFAs) to high
      physiological levels reduces insulin sensitivity. In sedentary humans,
      intramyocellular lipid (IMCL) is inversely related to insulin sensitivity. Since
      muscle fiber composition affects muscle metabolism, whether FFAs induce IMCL
      accumulation in a fiber type-specific manner remains unknown. We hypothesized
      that in the setting of acute FFA elevation by lipid infusion within the context
      of a hyperinsulinemic-euglycemic clamp, IMCL will preferentially accumulate in
      type 1 fibers. Normal-weight participants (n = 57, mean +/- SE: age 24 +/- 0.6
      yr, BMI 22.2 +/- 0.3 kg/m2) who were either endurance trained or sedentary by
      self-report were recruited from the University of Minnesota (n = 31, n = 15
      trained) and University of Pittsburgh (n = 26, n = 14 trained). All participants
      underwent a hyperinsulinemic-euglycemic clamp in the context of a 6-h infusion of
      either lipid or glycerol control. A vastus lateralis muscle biopsy was obtained
      at baseline and end-infusion (6 h). The muscle biopsies were processed and
      analyzed at the University of Pittsburgh for fiber type-specific IMCL
      accumulation by Oil-Red-O staining. Regardless of training status, acute
      elevation of FFAs to high physiological levels (~400-600 meq/l) increased IMCL
      preferentially in type 1 fibers (+35 +/- 11% compared with baseline, +29 +/- 11%
      compared with glycerol control: P < 0.05). The increase in IMCL correlated with a
      decline in insulin sensitivity as measured by the hyperinsulinemic-euglycemic
      clamp (r = -0.32, P < 0.01) independent of training status. Regardless of
      training status, increase of FFAs to a physiological range within the context of
      hyperinsulinemia shows preferential IMCL accumulation in type 1 fibers.NEW &
      NOTEWORTHY This novel human study examined the effects of FFA elevation in the
      setting of hyperinsulinemia on accumulation of fat in specific types of muscle
      fibers. Within the context of the hyperinsulinemic-euglycemic clamp, we found
      that an increase of FFAs to a physiological range sufficient to reduce insulin
      sensitivity is associated with preferential IMCL accumulation in type 1 fibers.

PMID- 28450551
TI  - Data collection, handling, and fitting strategies to optimize accuracy and
      precision of oxygen uptake kinetics estimation from breath-by-breath
      measurements.
AB  - Phase 2 pulmonary oxygen uptake kinetics (phi2 tauVo2P) reflect muscle oxygen
      consumption dynamics and are sensitive to changes in state of training or health.
      This study identified an unbiased method for data collection, handling, and
      fitting to optimize Vo2P kinetics estimation. A validated computational model of
      Vo2P kinetics and a Monte Carlo approach simulated 2 * 105 moderate-intensity
      transitions using a distribution of metabolic and circulatory parameters spanning
      normal health. Effects of averaging (interpolation, binning, stacking, or
      separate fitting of up to 10 transitions) and fitting procedures (biexponential
      fitting, or phi2 isolation by time removal, statistical, or derivative methods
      followed by monoexponential fitting) on accuracy and precision of Vo2P kinetics
      estimation were assessed. The optimal strategy to maximize accuracy and precision
      of tauVo2P estimation was 1-s interpolation of 4 bouts, ensemble averaged, with
      the first 20 s of exercise data removed. Contradictory to previous advice, we
      found optimal fitting procedures removed no more than 20 s of phi1 data.
      Averaging method was less critical: interpolation, binning, and stacking gave
      similar results, each with greater accuracy compared with analyzing repeated
      bouts separately. The optimal procedure resulted in phi2 tauVo2P estimates for
      transitions from an unloaded or loaded baseline that averaged 1.97 +/- 2.08 and
      1.04 +/- 2.30 s from true, but were within 2 s of true in only 47-62% of
      simulations. Optimized 95% confidence intervals for tauVo2P ranged from 4.08 to
      4.51 s, suggesting a minimally important difference of ~5 s to determine
      significant changes in tauVo2P during interventional and comparative studies.NEW
      & NOTEWORTHY We identified an unbiased method to maximize accuracy and precision
      of oxygen uptake kinetics (tauVo2P) estimation. The optimum number of bouts to
      average was four; interpolation, bin, and stacking averaging methods gave similar
      results. Contradictory to previous advice, we found that optimal fitting
      procedures removed no more than 20 s of phase 1 data. Our data suggest a
      minimally important difference of ~5 s to determine significant changes in
      tauVo2P during interventional and comparative studies.

PMID- 28450552
TI  - One-year costs of bilateral or single internal mammary grafts in the Arterial
      Revascularisation Trial.
AB  - OBJECTIVE: Coronary artery bypass grafting (CABG) using bilateral internal
      mammary arteries (BIMA) may improve survival over CABG using single internal
      mammary arteries (SIMA), but may be surgically more complex (and therefore
      costly) and associated with impaired sternal wound healing. We report, for the
      first time, a detailed comparison of healthcare resource use and costs over 12
      months, as part of the Arterial Revascularisation (ART) Trial. METHODS: 3102
      patients in 28 hospitals in seven countries were randomised to CABG surgery using
      BIMA (n=1548) or SIMA (n=1554). Detailed resource use data were collected
      covering surgery, the initial hospital episode, and for 12 months post
      randomisation. Using UK unit costs, total costs were calculated and compared
      between trial arms and for subgroups. RESULTS: Patients randomised to BIMA spent
      20 min longer in theatre (95% CI 15 to 25, p<0.001) and also required more
      treatment for sternal wound problems. Mean (SD) total costs per patient at 12
      months were L13 839 (L10 534) for BIMA and L12 717 (L9719) for SIMA (mean cost
      difference L1122, 95% CI L407 to L1838, p=0.002). No tests for interaction
      between subgroups and treatment allocation were significant. CONCLUSIONS: At 12
      months from randomisation, mean costs were approximately 9% higher in BIMA than
      SIMA patients, primarily due to longer time in theatre and in-hospital stay, and
      slightly higher costs related to sternal wound problems during follow-up. Follow
      up to the primary trial endpoint of 10 years will reveal whether longer-term
      differences emerge in graft patency or in overall survival. TRIAL REGISTRATION
      NUMBER: Controlled-trials.com (ISRCTN46552265).

PMID- 28450553
TI  - Epidemiological changes in Eisenmenger syndrome in the Nordic region in 1977
      2012.
AB  - OBJECTIVE: Improved diagnostic tools, timely closure of the shunt and a better
      understanding of the complexity of Eisenmenger syndrome (ES) have led to improved
      care and treatment in tertiary centres. These may have decreased the incidence of
      ES and improved survival of patients with ES, although evidence is still lacking.
      The aim of this study was to investigate temporal changes in incidence,
      prevalence and mortality in patients with ES for 35 years in the Nordic region.
      METHODS: This was a retrospective population-based study including 714 patients
      with ES. Survival analysis was performed based on all-cause mortality and
      accounting for immortal time bias. RESULTS: The incidence of ES decreased from
      2.5/million inhabitants/year in 1977 to 0.2/million inhabitants/year in 2012.
      Correspondingly, prevalence decreased from 24.6 to 11.9/million inhabitants. The
      median survival was 38.4 years, with 20-year, 40-year and 60-year survival of
      72.5%, 48.4%, and 21.3%, respectively. Complex lesions and Down syndrome were
      independently associated with worse survival (HR 2.2, p<0.001 and HR 1.8,
      p<0.001, respectively). Age at death increased from 27.7 years in the period from
      1977 to 1992, to 46.3 years from July 2006 to 2012 (p<0.001). CONCLUSIONS: The
      incidence and prevalence of ES in the Nordic region have decreased markedly
      during the last decades. Furthermore, the median age at death increased
      throughout the study period, indicating prolonged life expectancy in the ES
      population. However, increasing age represents decreased incidence, rather than
      improved survival. Nonetheless, longevity with ES is still shorter than in the
      background population.

PMID- 28450555
TI  - Integrating MRI and Chemokine Receptor CXCR4-Targeted PET for Detection of
      Leukocyte Infiltration in Complicated Urinary Tract Infections After Kidney
      Transplantation.
AB  - Complicated urinary tract infections (UTIs) are frequent in immunosuppressed
      patients after kidney transplantation and may lead to allograft failure or
      urosepsis. Noninvasive detection of allograft involvement as well as localization
      of the primary site of infection are challenging. Therefore, we sought to
      determine whether molecularly targeted PET, combined with diffusion-weighted MRI,
      enables detection of leukocytes in renal allografts. Methods: Thirteen kidney
      transplant recipients with complicated UTIs underwent both PET with a specific
      CXCR4 ligand, 68Ga-pentixafor, and diffusion-weighted MRI. The spatial
      distribution and intensity of CXCR4 upregulation in renal allografts as
      determined by SUVs on PET and diffusion restriction as determined by apparent
      diffusion coefficients (ADCs) on MRI were analyzed and compared with urinalysis,
      clinical chemistry and bacteriology, and biopsy, if available. Results: Combined
      PET/MRI detected acute allograft infection in 9 patients and lower
      UTI/nonurologic infections in the remaining 4 patients. Leukocyte infiltration
      was identified by areas of CXCR4 upregulation compared with unaffected parenchyma
      in PET (SUVmean, 4.6 vs. 3.7; P < 0.01), corresponding to areas with increased
      cell density in MRI (ADCmin, 0.89 vs. 1.59 * 10-3 mm2/s, P < 0.01). Allograft
      CXCR4 signal was paralleled by CXCR4 upregulation in lymphoid organs.
      Histopathologic evaluation supported a correlation between CXCR4 signal and
      presence of leukocytes. Conclusion: Combined CXCR4-targeted PET/MRI with 68Ga
      pentixafor may enable the noninvasive detection of leukocytes in renal
      allografts. This novel methodology may refine the characterization of infectious
      and inflammatory kidney diseases and may serve as a platform for future clinical
      studies targeting allograft infection.

PMID- 28450554
TI  - Biodistribution, Pharmacokinetics, and Dosimetry of 177Lu-, 90Y-, and 111In
      Labeled Somatostatin Receptor Antagonist OPS201 in Comparison to the Agonist
      177Lu-DOTATATE: The Mass Effect.
AB  - Radiolabeled somatostatin receptor (SSTR) antagonists have shown in vivo higher
      uptake in SSTR-expressing tumors than agonists. In this preclinical study, the
      SSTR2 antagonist OPS201 (DOTA-JR11; DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr
      Cys)-DTyr-NH2]) labeled with 177Lu, 90Y, and 111In was compared with the SSTR2
      agonist 177Lu-DOTATATE. Methods: Biodistribution, pharmacokinetics, SPECT/CT, and
      dosimetry studies were performed to assess the bioequivalence of all
      radiotracers. Use of escalated peptide mass and nephroprotective agents were
      systematically investigated. Results: The tumor residence time was 15.6 h (13.4
      17.7) for 177Lu-OPS201 (10 pmol) and 6.4 h (5.4-7.3) for 177Lu-DOTATATE,
      resulting in a 2.5-times-higher tumor dose for the antagonist than for the
      agonist (0.854 vs. 0.333 mGy/MBq for a 4-cm tumor). The overall tumor-to-kidney
      dose ratio was approximately 24% and 32% higher for 177Lu-OPS201 than for 90Y
      OPS201 and 177Lu-DOTATATE, respectively. 111In-OPS201 had a biodistribution
      significantly different from 90Y-OPS201 and is therefore not a surrogate for 90Y
      OPS201 dosimetry studies. Importantly, and in contrast to 177Lu-DOTATATE,
      injection of 10, 200, and 2,000 pmol of 177Lu-OPS201 did not cause any relevant
      tumor saturation, with tumor uptake 4 h after injection: 23.9, 24.9, and 18.8
      percentage of injected activity per gram of tissue (%IA/g), respectively, for the
      antagonist (P > 0.05), as compared with 17.8, 12.0, and 9.9 %IA/g for the agonist
      (P < 0.05). Increasing the peptide mass of 177Lu-OPS201 from 10 to 200 pmol
      drastically decreased the effective dose from 0.0908 to 0.0184 mSv/MBq and
      decreased the uptake in the liver, bone marrow, and all SSTR2-expressing organs;
      thus, the therapeutic index improved considerably. Lysine and succinylated
      gelatine, alone or in combination, significantly reduced the renal dose of 177Lu
      OPS201 compared with the control group, by 45%, 25%, and 40%, respectively (P <
      0.05). The reduction was similar for 10 and 200 pmol, whereas lysine performed
      better than succinylated gelatine. Conclusion:177Lu-OPS201 exhibits higher tumor
      uptake, longer tumor residence time, and improved tumor-to-kidney dose ratio
      compared with 177Lu-DOTATATE and 90Y-OPS201. Importantly, the mass-escalation
      study indicates that an optimized antagonist mass might further improve the
      safety window of peptide receptor radionuclide therapy by reducing the liver and
      bone marrow doses as well as the effective dose. Clinical studies are warranted
      to confirm the efficacy and advantageous toxicity profile of 177Lu-OPS201.

PMID- 28450557
TI  - Regarding "Subjecting Radiologic Imaging to the Linear No-Threshold Hypothesis: A
      Non Sequitur of Non-Trivial Proportion".

PMID- 28450556
TI  - Improved Detection of Transosseous Meningiomas Using 68Ga-DOTATATE PET/CT
      Compared with Contrast-Enhanced MRI.
AB  - 68Ga-DOTATATE PET/CT enables detection of meningioma tissue based on somatostatin
      receptor 2 expression. Transosseous extension of intracranial meningiomas is
      known to be an important risk factor for tumor recurrence and patient mortality.
      We analyzed the diagnostic performance of 68Ga-DOTATATE PET/CT and contrast
      enhanced MRI (CE-MRI) for the detection of osseous infiltration using qualitative
      and quantitative imaging parameters. Methods: In this institutional review board
      approved retrospective study, subjects were selected from 327 consecutive 68Ga
      DOTATATE PET/CT examinations for evaluation of confirmed or suspected meningioma.
      Inclusion criteria were CE-MRI within 30 d and pathology-confirmed meningioma
      diagnosis with inclusion or exclusion of transosseous extension as the standard
      of reference. Imaging was analyzed by two readers. Tracer uptake values and
      meningioma volumes were determined. chi2, Mann-Whitney U, Wilcoxon signed rank,
      and McNemar tests, as well as receiver-operating-characteristic analyses, were
      performed to compare variables and diagnostic performance. Results: Eighty-two
      patients fulfilled the inclusion criteria. Patients with transosseous extension
      of meningioma (n = 67) showed significantly larger lesions (median, 12.8 vs. 3.3
      mL; P < 0.001) and significantly higher tracer uptake values (median SUVmax, 14.2
      vs. 7.6; P = 0.011) than patients with extraosseous meningiomas (n = 15). 68Ga
      DOTATATE PET/CT in comparison to CE-MRI performed at a higher sensitivity (98.5%
      vs. 53.7%) while maintaining high specificity (86.7% vs. 93.3%) in the detection
      of osseous involvement (P < 0.001). In receiver-operating-characteristic
      analysis, PET/CT assessment performed better than CE-MRI (area under the curve,
      0.932 vs. 0.773). PET/CT- and CE-MRI-based volume estimation yielded comparable
      results for extraosseous meningiomas (P = 0.132) and the extraosseous part of
      transosseous meningiomas (P = 0.636), whereas the volume of the intraosseous part
      was assessed as significantly larger by PET/CT (P < 0.001). Conclusion:68Ga
      DOTATATE PET/CT enables improved detection of the transosseous extension of
      intracranial meningiomas compared with CE-MRI.

PMID- 28450559
TI  - Reply: The Need for Prudence When Using 18F-FDG PET as a Reference Standard for
      Lymphoma Detection.

PMID- 28450558
TI  - Metabolic and Molecular Imaging of Atherosclerosis and Venous Thromboembolism.
AB  - Metabolic and molecular imaging continues to advance our understanding of
      vascular disease pathophysiology. At present, 18F-FDG PET imaging is the most
      widely used clinical tool for metabolic and molecular imaging of atherosclerosis.
      However, novel nuclear tracers and intravascular optical near-infrared
      fluorescence imaging catheters are emerging to assess new biologic targets in
      vivo and in coronary arteries. This review highlights current metabolic and
      molecular imaging clinical and near-clinical applications within atherosclerosis
      and venous thromboembolism, and explores the potential for metabolic and
      molecular imaging to affect patient-level risk prediction and disease treatment.

PMID- 28450560
TI  - High-Contrast PET Imaging of Vasopressin V1B Receptors with a Novel Radioligand,
      11C-TASP699.
AB  - Vasopressin 1B receptors (V1BRs) are abundantly expressed in the pituitary, and
      in vivo PET of V1BRs was recently enabled by our development of a specific
      radioligand, 11C-TASP0434299, derivatized from pyridopyrimidin-4-one. Here, we
      identified a novel pyridopyrimidin-4-one analog, N-tert-butyl-2-[2-(6-11C
      methoxypyridine-2-yl)-6-[3-(morpholin-4-yl)propoxy]-4-oxopyrido[2,3-d]pyrimidin
      3(4H)-yl]acetamide (11C-TASP0410699, hereafter referred to as 11C-TASP699), as a
      potent V1BR radioligand producing a higher image contrast for the target than 11C
      TASP0434299. Methods: In vitro properties of TASP699 were assessed by assaying
      its affinity for human V1BR and its selectivity for off-target molecules.
      Radioactive uptake in the pituitary was analyzed using PET in rhesus monkeys
      after intravenous administration of 11C-TASP699. Serial doses of a selective V1BR
      antagonist, 2-[2-(3-chloro-4-fluorophenyl)-6-[3-(morpholin-4-yl)propoxy]-4
      oxopyrido[2,3-d]pyrimidin-3(4H)-yl]-N-isopropylacetamide hydrochloride
      (TASP0390325), were administered before the radioligand injection.
      Autoradiographic labeling of monkey pituitary slices with 11C-TASP699 was
      conducted with or without nonradioactive V1BR antagonists. Results: The half
      maximal inhibitory concentration (IC50) of TASP699 for human V1BRs (0.165 nM) was
      lower than that of TASP0434299 (0.526 nM), whereas its IC50 values for off-target
      molecules exceeded 1 MUM. PET imaging in monkeys demonstrated that the peak
      pituitary uptake of 11C-TASP699 was almost equivalent to that of 11C-TASP0434299
      and that pretreatment with TASP0390325 inhibited the retention of 11C-TASP699 in
      a dose-dependent manner, inducing nearly full occupancy at 0.3 mg/kg. Specific
      radioligand binding was determined as a specific-to-nondisplaceable uptake ratio
      at equilibrium using radioactivity retentions at 60 min in baseline and blocking
      studies. This ratio for 11C-TASP699 was approximately 2.5-fold greater than that
      of 11C-TASP0434299. A reversed-phase high-performance liquid chromatography study
      identified the parent and polar radiometabolites. Affinities of 2 predicted
      metabolite candidates for V1BRs were more than 10 times weaker than that of the
      parent. Intense autoradiographic labeling of the anterior pituitary with 11C
      TASP699 was inhibited with TASP0390325 in a concentration-dependent manner.
      Conclusion:11C-TASP699 yielded PET images of pituitary V1BRs with a higher
      contrast than 11C-TASP0434299, supporting the applicability of 11C-TASP699 in the
      assessment of neuropsychiatric diseases and dose findings for test drugs in
      clinical trials.

PMID- 28450561
TI  - Prognostic Value of Myocardial Perfusion Imaging with a Cadmium-Zinc-Telluride
      SPECT Camera in Patients Suspected of Having Coronary Artery Disease.
AB  - The prognostic value of myocardial perfusion imaging (MPI) with the cadmium-zinc
      telluride (CZT) SPECT camera is not well established. Therefore, the aim of the
      current study was to evaluate the prognostic value of MPI performed with a CZT
      SPECT camera in a large cohort of patients suspected of having coronary artery
      disease. Methods: Consecutive symptomatic stable patients (n = 4,057) without a
      history of coronary artery disease underwent CZT SPECT MPI. During a median
      follow-up of 2.4 y (25th-75th percentile, 1.7-3.4), patients were monitored for
      primary (nonfatal myocardial infarction and cardiac mortality) and secondary
      outcomes (late revascularization [>90 d after scanning] and primary outcome).
      Results: Patients with normal perfusion demonstrated low annual event rates
      (primary outcome, 0.2%; secondary outcome, 0.6%). Annual event rates increased
      with the extent of abnormality of myocardial perfusion. In patients with small
      ischemic perfusion defects, annual event rates were 0.7% and 2.8% for the primary
      and secondary outcome, respectively. In patients with moderate or large ischemic
      perfusion defects, these event rates were 1.2% and 4.3%, respectively. After
      multivariate analysis, the risk for events was significantly associated with the
      extent of ischemia (hazard ratio for small ischemic defects: 2.2, 95% confidence
      interval [CI], 0.9-5.9 and 4.6, 95% CI, 2.8-7.6, for primary and secondary
      outcomes, respectively; hazard ratio for moderate or large ischemic defects: 4.0,
      95% CI, 1.5-10.5 and 12.1, 95% CI, 7.2-20.2, for primary and secondary outcomes,
      respectively). Conclusion: Our findings show that MPI acquired with a CZT SPECT
      camera provides excellent prognostic information, with low event rates in
      patients with normal myocardial perfusion. In patients with abnormal SPECT MPI,
      the extent of abnormality is independently associated with an increased risk of
      events.

PMID- 28450562
TI  - Dual-Target Binding Ligands with Modulated Pharmacokinetics for Endoradiotherapy
      of Prostate Cancer.
AB  - Prostate-specific membrane antigen (PSMA)-targeted radiotherapy of prostate
      cancer (PCa) has emerged recently as a promising approach to the treatment of
      disseminated disease. A small number of ligands have been evaluated in patients,
      and although early tumor response is encouraging, relapse rate is high and these
      compounds localize to the parotid, salivary, and lacrimal glands as well as to
      the kidney, leading to dose-limiting toxicities and adverse events affecting
      quality of life. We envision that dual-target binding ligands displaying high
      affinity for PSMA and appropriate affinity for human serum albumin (HSA) may
      demonstrate a higher therapeutic index and be suitable for treatment of PCa by
      targeted alpha-therapy. Methods: Six novel urea-based ligands with varying
      affinities for PSMA and HSA were synthesized, labeled with 131I, and evaluated by
      in vitro binding and uptake assays in LNCaP cells. Four compounds were advanced
      for further evaluation in a preclinical model of PCa. The compounds were compared
      with MIP-1095, a PSMA ligand currently in clinical evaluation. Results: The
      compounds demonstrated affinity for PSMA on the order of 4-40 nM and affinity for
      HSA in the range of 1-53 MUM. Compounds with relatively high affinity for HSA
      (<=2 MUM) showed high and sustained blood-pool activity and reduced uptake in the
      kidneys. 131I-RPS-027, with a 50% inhibitory concentration (PSMA) of 15 nM and a
      dissociation constant (HSA) of 11.2 MUM, cleared from the blood over the course
      of 48 h and showed good tumor uptake (10 percentage injected dose per gram) and
      retention and a greater than 5-fold decrease in kidney uptake relative to MIP
      1095. The tumor-to-kidney ratio of 131I-RPS-027 was greater than 3:1 at 24 h
      after injection, increasing to 7:1 by 72 h. Conclusion: RPS-027 shows dual
      targeting to PSMA and albumin, resulting in a high tumor uptake, highly favorable
      tissue distribution, and promising therapeutic profile in a preclinical model of
      prostate cancer. In comparison to existing ligands proposed for targeted therapy
      of prostate cancer, RPS-027 has tumor-to-tissue ratios that predict a significant
      reduction in side effects during therapy. Using iodine/radioiodine as a surrogate
      for the radiohalogen 211At, we therefore propose dual-target binding ligands such
      as RPS-027 as next-generation radiopharmaceuticals for targeted alpha-therapy
      using 211At.

PMID- 28450563
TI  - SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled
      Somatostatin Receptor Antagonists?
AB  - Recent studies have shown enhanced tumor targeting by novel somatostatin receptor
      (SSTR) antagonists compared with clinically widely used agonists. However, these
      results have been obtained mostly in neuroendocrine tumors, and only limited data
      are available for cancer types with lower SSTR expression, including breast
      cancer (BC). To date, two studies have reported higher binding of the antagonist
      than the agonist in BC, but in both studies only a limited number of cases were
      evaluated. In this preclinical study, we further investigated whether the
      application of an SSTR antagonist can improve SSTR-mediated BC imaging in a large
      panel of BC specimens. We also generated an in vivo BC mouse model and performed
      SPECT/MRI and biodistribution studies. Methods: Binding of 111In-DOTA-Tyr3
      octreotate (SSTR agonist) and 111In-DOTA-JR11 (SSTR antagonist) to 40 human BC
      specimens was compared using in vitro autoradiography. SSTR2 immunostaining was
      performed to confirm SSTR2 expression of the tumor cells. Furthermore, binding of
      the radiolabeled SSTR agonist and antagonist was analyzed in tissue material from
      6 patient-derived xenografts. One patient-derived xenograft, the estrogen
      receptor-positive model T126, was chosen to generate in vivo mouse models
      containing orthotopic breast tumors for in vivo SPECT/MRI and biodistribution
      studies after injection with 177Lu-DOTA-Tyr3-octreotate or 177Lu-DOTA-JR11.
      Results:111In-DOTA-JR11 binding to human BC tissue was significantly higher than
      111In-DOTA-Tyr3-octreotate binding (P < 0.001). The median ratio of antagonist
      binding versus agonist binding was 3.39 (interquartile range, 2-5). SSTR2
      immunostaining confirmed SSTR2 expression on the tumor cells. SPECT/MRI of the
      mouse model found better tumor visualization with the antagonist. This result was
      in line with the significantly higher tumor uptake of the radiolabeled antagonist
      than of the agonist as measured in biodistribution studies 285 min after
      radiotracer injection (percentage injected dose per gram of tissue: 1.92 +/- 0.43
      vs. 0.90 +/- 0.17; P = 0.002). Conclusion: SSTR antagonists are promising
      candidates for BC imaging.

PMID- 28450565
TI  - Reply: Fixed 3.7-GBq 131I Activity for Metastatic Thyroid Cancer Therapy Ignores
      Science and History.

PMID- 28450564
TI  - Diagnostic PET Imaging of Mammary Microcalcifications Using 64Cu-DOTA-Alendronate
      in a Rat Model of Breast Cancer.
AB  - The development of improved breast cancer screening methods is hindered by a lack
      of cancer-specific imaging agents and effective small-animal models to test them.
      The purpose of this study was to evaluate 64Cu-DOTA-alendronate as a mammary
      microcalcification-targeting PET imaging agent, using an ideal rat model. Our
      long-term goal is to develop 64Cu-DOTA-alendronate for the detection and
      noninvasive differentiation of malignant versus benign breast tumors with PET.
      Methods: DOTA-alendronate was synthesized, radiolabeled with 64Cu, and
      administered to normal or tumor-bearing aged, female, retired breeder Sprague
      Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged
      with light, confocal, and electron microscopy to verify microcalcification
      targeting specificity of DOTA-alendronate and elucidate the histologic and
      ultrastructural characteristics of the microcalcifications in different mammary
      tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed
      to evaluate the efficacy and safety of 64Cu-DOTA-alendronate. Results:64Cu-DOTA
      alendronate was radiolabeled with a 98% yield. PET imaging using aged, female,
      retired breeder rats showed specific binding of 64Cu-DOTA-alendronate in mammary
      glands and mammary tumors. The highest uptake of 64Cu-DOTA-alendronate was in
      malignant tumors and the lowest uptake in benign tumors and normal mammary
      tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the
      microcalcification binding specificity of alendronate derivatives.
      Biodistribution studies revealed tissue alendronate concentrations peaking within
      the first hour, then decreasing over the next 48 h. Our dosimetric analysis
      demonstrated a 64Cu effective dose within the acceptable range for clinical PET
      imaging agents and the potential for translation into human patients.
      Conclusion:64Cu-DOTA-alendronate is a promising PET imaging agent for the
      sensitive and specific detection of mammary tumors as well as the differentiation
      of malignant versus benign tumors based on absolute labeling uptake.

PMID- 28450566
TI  - Studies of a Next-Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT
      System.
AB  - This article presents system performance studies for the Discovery MI PET/CT
      system, a new time-of-flight system based on silicon photomultipliers. System
      performance and clinical imaging were compared between this next-generation
      system and other commercially available PET/CT and PET/MR systems, as well as
      between different reconstruction algorithms. Methods: Spatial resolution,
      sensitivity, noise-equivalent counting rate, scatter fraction, counting rate
      accuracy, and image quality were characterized with the National Electrical
      Manufacturers Association NU-2 2012 standards. Energy resolution and coincidence
      time resolution were measured. Tests were conducted independently on two
      Discovery MI scanners installed at Stanford University and Uppsala University,
      and the results were averaged. Back-to-back patient scans were also performed
      between the Discovery MI, Discovery 690 PET/CT, and SIGNA PET/MR systems.
      Clinical images were reconstructed using both ordered-subset expectation
      maximization and Q.Clear (block-sequential regularized expectation maximization
      with point-spread function modeling) and were examined qualitatively. Results:
      The averaged full widths at half maximum (FWHMs) of the radial/tangential/axial
      spatial resolution reconstructed with filtered backprojection at 1, 10, and 20 cm
      from the system center were, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm,
      and 7.53/4.90/6.10 mm. The averaged sensitivity was 13.7 cps/kBq at the center of
      the field of view. The averaged peak noise-equivalent counting rate was 193.4
      kcps at 21.9 kBq/mL, with a scatter fraction of 40.6%. The averaged contrast
      recovery coefficients for the image-quality phantom were 53.7, 64.0, 73.1, 82.7,
      86.8, and 90.7 for the 10-, 13-, 17-, 22-, 28-, and 37-mm-diameter spheres,
      respectively. The average photopeak energy resolution was 9.40% FWHM, and the
      average coincidence time resolution was 375.4 ps FWHM. Clinical image comparisons
      between the PET/CT systems demonstrated the high quality of the Discovery MI.
      Comparisons between the Discovery MI and SIGNA showed a similar spatial
      resolution and overall imaging performance. Lastly, the results indicated
      significantly enhanced image quality and contrast-to-noise performance for
      Q.Clear, compared with ordered-subset expectation maximization. Conclusion:
      Excellent performance was achieved with the Discovery MI, including 375 ps FWHM
      coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between
      reconstruction algorithms and other multimodal silicon photomultiplier and non
      silicon photomultiplier PET detector system designs indicated that performance
      can be substantially enhanced with this next-generation system.

PMID- 28450567
TI  - Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden in
      Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer: 18F-FDG
      PET/CT Study.
AB  - We aimed to evaluate the relationships between circulating tumor cells (CTCs) or
      plasma cell-free DNA (cfDNA) on one side and a comprehensive range of 18F-FDG
      PET/CT-derived parameters on the other side in chemotherapy-naive patients with
      advanced non-small cell lung cancer (NSCLC). Methods: From a group of 79 patients
      included in a trial evaluating the role of pretreatment circulating tumor markers
      as predictors of prognosis in chemotherapy-naive patients with advanced NSCLC, we
      recruited all those who underwent 18F-FDG PET/CT for clinical reasons at our
      institution before inclusion in the trial (and thus just before chemotherapy).
      For each patient, a peripheral blood sample was collected at baseline for the
      evaluation of CTCs and cfDNA. CTCs were isolated by size using a filtration-based
      device and then morphologically identified and enumerated; cfDNA was isolated
      from plasma and quantified by a quantitative polymerase chain reaction using
      human telomerase reverse transcriptase. The following 18F-FDG PET/CT-derived
      parameters were computed: maximum diameter of the primary lesion (T), of the
      largest lymph node (N), and of the largest metastatic lesion (M); SUVmax;
      SUVmean; size-incorporated SUVmax; metabolic tumor volume; and total lesion
      glycolysis. All parameters were independently measured for T, N, and M. The
      associations among CTCs, cfDNA, and 18F-FDG PET/CT-derived parameters were
      evaluated by multivariate-analysis. Patients were divided into 2 groups according
      to the presence of either limited metastatic involvement (M1a or M1b due to
      extrathoracic lymph nodes only) or disseminated metastatic disease. The presence
      or absence of metabolically active bone lesions was also recorded for each
      patient, and patient subgroups were compared. Results: Thirty-seven patients
      recruited in the trial matched our PET-based criteria (24 men; age, 64.5 +/- 8.1
      y). SUVmax for the largest metastatic lesion was the only variable independently
      associated with baseline cfDNA levels (P = 0.016). Higher levels of cfDNA were
      detected in the subgroup of patients with metabolically active bone lesions (P =
      0.02), but no difference was highlighted when patients with more limited
      metastatic disease were compared with patients with disseminated metastatic
      disease. Conclusion: The correlation of cfDNA levels with tumor metabolism, but
      not with metabolic tumor volume at regional or distant levels, suggests that
      cfDNA may better reflect tumor biologic behavior or aggressiveness rather than
      tumor burden in metastatic NSCLC.

PMID- 28450568
TI  - Wet or Dry? Do Liquid Biopsy Techniques Compete with or Complement PET for
      Disease Monitoring in Oncology?

PMID- 28450569
TI  - 18F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes:
      Detection Rate, Image Quality, Activity Kinetics, and Biodistribution.
AB  - There is increasing interest in PET/CT with prostate-specific membrane antigen
      (PSMA) tracers for imaging of prostate cancer because of the higher detection
      rates of prostate cancer lesions than with PET/CT with choline. For 68Ga-PSMA-11
      tracers, late imaging at 180 min after injection instead of imaging at 45-60 min
      after injection improves the detection of prostate cancer lesions. For 18F
      DCFPyL, improved detection rates have recently been reported in a small pilot
      study. In this study, we report the effects of PET/CT imaging at 120 min after
      injection of 18F-DCFPyL in comparison to images acquired at 60 min after
      injection in a larger clinical cohort of 66 consecutive patients with
      histopathologically proven prostate cancer. Methods: Images were acquired 60 and
      120 min after injection of 18F-DCFPyL. We report the positive lesions specified
      for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant
      lymph nodes, bone, and others) at both time points by visual analysis, the image
      quality at both time points, and a semiquantitative analysis of the tracer
      activity in both prostate cancer lesions as well as normal tissues at both time
      points. Results: Our data showed a significantly increasing uptake of 18F-DCFPyL
      between 60 and 120 min after injection in 203 lesions characteristic for prostate
      cancer (median, 10.78 vs. 12.86, P < 0.001, Wilcoxon signed-rank test). By visual
      analysis, 38.5% of all patients showed more lesions using images at 120 min after
      injection than using images at 60 min after injection, and in 9.2% a change in
      TNM staging was found. All lesions seen on images 60 min after injection were
      also visible on images 120 min after injection. A significantly better mean
      signal-to-noise ratio of 11.93 was found for images acquired 120 min after
      injection (P < 0.001, paired t test; signal-to-noise ratio at 60 min after
      injection, 11.15). Conclusion:18F-DCFPyL PET/CT images at 120 min after injection
      yield a higher detection rate of prostate cancer characteristic lesions than
      images at 60 min after injection. Further studies are needed to elucidate the
      best imaging time point for 18F-DCFPyL.

PMID- 28450570
TI  - Genomics trumps clinical criteria in BMT? Nyet!

PMID- 28450571
TI  - Encore! Oral therapy for type 1 Gaucher disease.

PMID- 28450572
TI  - Understanding CML, 1 cell at a time.

PMID- 28450573
TI  - EZH! The IRE of DLBCL gets an UPR hand.

PMID- 28450574
TI  - A major turning point in NK/T-cell lymphoma?

PMID- 28450575
TI  - Ribosomes in platelets protect the messenger.

PMID- 28450576
TI  - De novo Richter transformation.

PMID- 28450577
TI  - The thin line between CML and CMML.

PMID- 28450578
TI  - Integrated Assessment of Diclofenac Biotransformation, Pharmacokinetics, and
      Omics-Based Toxicity in a Three-Dimensional Human Liver-Immunocompetent Coculture
      System.
AB  - In vitro hepatocyte culture systems have inherent limitations in capturing known
      human drug toxicities that arise from complex immune responses. Therefore, we
      established and characterized a liver immunocompetent coculture model and
      evaluated diclofenac (DCF) metabolic profiles, in vitro-in vivo clearance
      correlations, toxicological responses, and acute phase responses using liquid
      chromatography-tandem mass spectrometry. DCF biotransformation was assessed after
      48 hours of culture, and the major phase I and II metabolites were similar to the
      in vivo DCF metabolism profile in humans. Further characterization of secreted
      bile acids in the medium revealed that a glycine-conjugated bile acid was a
      sensitive marker of dose-dependent toxicity in this three-dimensional liver
      microphysiological system. Protein markers were significantly elevated in the
      culture medium at high micromolar doses of DCF, which were also observed
      previously for acute drug-induced toxicity in humans. In this immunocompetent
      model, lipopolysaccharide treatment evoked an inflammatory response that resulted
      in a marked increase in the overall number of acute phase proteins. Kupffer cell
      mediated cytokine release recapitulated an in vivo proinflammatory response
      exemplified by a cohort of 11 cytokines that were differentially regulated after
      lipopolysaccharide induction, including interleukin (IL)-1beta, IL-1Ra, IL-6, IL
      8, IP-10, tumor necrosis factor-alpha, RANTES (regulated on activation normal T
      cell expressed and secreted), granulocyte colony-stimulating factor, macrophage
      colony-stimulating factor, macrophage inflammatory protein-1beta, and IL-5. In
      summary, our findings indicate that three-dimensional liver microphysiological
      systems may serve as preclinical investigational platforms from the perspective
      of the discovery of a set of clinically relevant biomarkers including potential
      reactive metabolites, endogenous bile acids, excreted proteins, and cytokines to
      predict early drug-induced liver toxicity in humans.

PMID- 28450580
TI  - Longitude Position in a Time Zone and Cancer Risk in the United States.
AB  - Background: Circadian disruption is a probable human carcinogen. From the eastern
      to western border of a time zone, social time is equal, whereas solar time is
      progressively delayed, producing increased discrepancies between individuals'
      social and biological circadian time. Accordingly, western time zone residents
      experience greater circadian disruption and may be at an increased risk of
      cancer.Methods: We examined associations between the position in a time zone and
      age-standardized county-level incidence rates for total cancers combined and 23
      specific cancers by gender using the data of the Surveillance, Epidemiology, and
      End Results Program (2000-2012), including four million cancer diagnoses in white
      residents of 607 counties in 11 U.S. states. Log-linear regression was conducted,
      adjusting for latitude, poverty, cigarette smoking, and state. Bonferroni
      corrected P values were used as the significance criteria.Results: Risk increased
      from east to west within a time zone for total and for many specific cancers,
      including chronic lymphocytic leukemia (both genders) and cancers of the stomach,
      liver, prostate, and non-Hodgkin lymphoma in men and cancers of the esophagus,
      colorectum, lung, breast, and corpus uteri in women.Conclusions: Risk increased
      from the east to the west in a time zone for total and many specific cancers, in
      accord with the circadian disruption hypothesis. Replications in analytic
      epidemiologic studies are warranted.Impact: Our findings suggest that circadian
      disruption may not be a rare phenomenon affecting only shift workers, but is
      widespread in the general population with broader implications for public health
      than generally appreciated. Cancer Epidemiol Biomarkers Prev; 26(8); 1306-11.
      (c)2017 AACR.

PMID- 28450579
TI  - Characterization of the Tissue Distribution of the Mouse Cyp2c Subfamily by
      Quantitative PCR Analysis.
AB  - The CYP2C subfamily of the cytochrome P450 gene superfamily encodes heme-thiolate
      proteins that have a myriad of biologic functions. CYP2C proteins detoxify
      xenobiotics and metabolize endogenous lipids such as arachidonic acid to
      bioactive eicosanoids. We report new methods and results for the quantitative
      polymerase reaction (qPCR) analysis for the 15 members of the mouse Cyp2c
      subfamily (Cyp2c29, Cyp2c37, Cyp2c38, Cyp2c39, Cyp2c40, Cyp2c44, Cyp2c50,
      Cyp2c54, Cyp2c55, Cyp2c65, Cyp2c66, Cyp2c67, Cyp2c68, Cyp2c69, and Cyp2c70).
      Commercially available TaqMan primer/probe assays were compared with developed
      SYBR Green primer sets for specificity toward the mouse Cyp2c cDNAs and analysis
      of their tissue distribution. TaqMan primer/probe assays for 10 of the mouse
      Cyp2c isoforms were shown to be specific for their intended mouse Cyp2c cDNA;
      however, there were no TaqMan primer/probe assays specific for the mouse Cyp2c29,
      Cyp2c40, Cyp2c67, Cyp2c68, or Cyp2c69 transcripts. Each of the SYBR Green primer
      sets was specific for its intended mouse Cyp2c cDNA. The two qPCR methods
      confirmed similar patterns of Cyp2c tissue expression: Cyp2c37, Cyp2c38, Cyp2c39,
      Cyp2c44, Cyp2c50, Cyp2c54, and Cyp2c70 were most highly expressed in liver;
      Cyp2c55 was highly expressed in large intestine; Cyp2c65 was highly expressed in
      stomach, duodenum, and large intestine; and Cyp2c66 was highly expressed in both
      duodenum and jejunum. For isoforms without specific TaqMan primer/probe assays,
      the SYBR Green primer sets detected high level expression of Cyp2c29, Cyp2c40,
      Cyp2c67, Cyp2c68, and Cyp2c69 in the liver. Lower expression levels of the mouse
      Cyp2cs were also detected in other tissues.

PMID- 28450581
TI  - Barriers to timely discharge from the general medicine service at an academic
      teaching hospital.
AB  - BACKGROUND: Reducing delays for patients who are safe to be discharged is
      important for minimising complications, managing costs and improving quality.
      Barriers to discharge include placement, multispecialty coordination of care and
      ineffective communication. There are a few recent studies that describe barriers
      from the perspective of all members of the multidisciplinary team. STUDY
      OBJECTIVE: To identify the barriers to discharge for patients from our medicine
      service who had a discharge delay of over 24 hours. METHODOLOGY: We developed and
      implemented a biweekly survey that was reviewed with attending physicians on each
      of the five medicine services to identify patients with an unnecessary delay.
      Separately, we conducted interviews with staff members involved in the discharge
      process to identify common barriers they observed on the wards. RESULTS: Over the
      study period from 28 October to 22 November 2013, out of 259 total discharges, 87
      patients had a delay of over 24 hours (33.6%) and experienced a total of 181
      barriers. The top barriers from the survey included patient readiness, prolonged
      wait times for procedures or results, consult recommendations and facility
      placement. A total of 20 interviews were conducted, from which the top barriers
      included communication both between staff members and with the patient, timely
      notification of discharge and lack of discharge standardisation. CONCLUSIONS:
      There are a number of frequent barriers to discharge encountered in our hospital
      that may be avoidable with planning, effective communication methods, more timely
      preparation and tools to standardise the discharge process.

PMID- 28450585
TI  - News at a glance.

PMID- 28450584
TI  - Syria, slums, and health security.

PMID- 28450583
TI  - RETINOBLASTOMA RELATED1 mediates germline entry in Arabidopsis.
AB  - To produce seeds, flowering plants need to specify somatic cells to undergo
      meiosis. Here, we reveal a regulatory cascade that controls the entry into
      meiosis starting with a group of redundantly acting cyclin-dependent kinase (CDK)
      inhibitors of the KIP-RELATED PROTEIN (KRP) class. KRPs function by restricting
      CDKA;1-dependent inactivation of the Arabidopsis Retinoblastoma homolog RBR1. In
      rbr1 and krp triple mutants, designated meiocytes undergo several mitotic
      divisions, resulting in the formation of supernumerary meiocytes that give rise
      to multiple reproductive units per future seed. One function of RBR1 is the
      direct repression of the stem cell factor WUSCHEL (WUS), which ectopically
      accumulates in meiocytes of triple krp and rbr1 mutants. Depleting WUS in rbr1
      mutants restored the formation of only a single meiocyte.

PMID- 28450586
TI  - An unprecedented march for science.

PMID- 28450587
TI  - Meet the science marchers.

PMID- 28450588
TI  - Private fusion machines aim to beat massive global effort.

PMID- 28450589
TI  - Claim of very early humans in Americas shocks researchers.

PMID- 28450582
TI  - Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain
      Somatic Mosaicism Network.
AB  - Neuropsychiatric disorders have a complex genetic architecture. Human genetic
      population-based studies have identified numerous heritable sequence and
      structural genomic variants associated with susceptibility to neuropsychiatric
      disease. However, these germline variants do not fully account for disease risk.
      During brain development, progenitor cells undergo billions of cell divisions to
      generate the ~80 billion neurons in the brain. The failure to accurately repair
      DNA damage arising during replication, transcription, and cellular metabolism
      amid this dramatic cellular expansion can lead to somatic mutations. Somatic
      mutations that alter subsets of neuronal transcriptomes and proteomes can, in
      turn, affect cell proliferation and survival and lead to neurodevelopmental
      disorders. The long life span of individual neurons and the direct relationship
      between neural circuits and behavior suggest that somatic mutations in small
      populations of neurons can significantly affect individual neurodevelopment. The
      Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both
      in neurotypical human brains and in the context of complex neuropsychiatric
      disorders.

PMID- 28450590
TI  - In surprise, tooth decay afflicts hunter-gatherers.

PMID- 28450591
TI  - DNA from cave soil reveals ancient human occupants.

PMID- 28450592
TI  - The vaccine wars.

PMID- 28450593
TI  - The science of persuasion.

PMID- 28450594
TI  - Vaccine myths.

PMID- 28450595
TI  - Vaccines on trial.

PMID- 28450596
TI  - The natural capital of city trees.

PMID- 28450597
TI  - A crossroad of neuronal diversity to build circuitry.

PMID- 28450598
TI  - Linking stem cells to germ cells.

PMID- 28450599
TI  - Extracting the contents of living cells.

PMID- 28450600
TI  - H. Boyd Woodruff (1917-2017).

PMID- 28450601
TI  - What lies beneath.

PMID- 28450603
TI  - Scienceblind: Why Our Intuitive Theories About the World Are So Often Wrong.

PMID- 28450602
TI  - A state of denial.

PMID- 28450604
TI  - Mexico's invasive species plan in context.

PMID- 28450606
TI  - Nature's treasure hunt.

PMID- 28450607
TI  - Bridges, not walls?

PMID- 28450605
TI  - Community network for deaf scientists.

PMID- 28450608
TI  - S&T Policy Forum examines evolving opioid epidemic.

PMID- 28450609
TI  - Forum's fight for science.

PMID- 28450611
TI  - Pattern formation in the brain.

PMID- 28450610
TI  - Aspiring to do better than one's parents.

PMID- 28450612
TI  - Getting phosphorus into healthy shape.

PMID- 28450613
TI  - Taking a look at fungal bioluminescence.

PMID- 28450614
TI  - Imaging an atomic soliton train.

PMID- 28450615
TI  - Zinc can compete with lithium.

PMID- 28450617
TI  - Sensitive and specific CRISPR diagnostics.

PMID- 28450616
TI  - Ancient genomics of horse domestication.

PMID- 28450619
TI  - Single-cell diversity in the brain.

PMID- 28450618
TI  - Thinking local about building.

PMID- 28450620
TI  - Germ cells on demand.

PMID- 28450621
TI  - An old cancer drug's degrading new look.

PMID- 28450622
TI  - Solar heat helps harvest humidity.

PMID- 28450623
TI  - Using quasar pairs to measure smoothness.

PMID- 28450624
TI  - When forces depend on orientation.

PMID- 28450625
TI  - Plant the right tree.

PMID- 28450627
TI  - Liver T cells in obesity-associated diabetes.

PMID- 28450626
TI  - Interferon-independent antiviral defense.

PMID- 28450628
TI  - An antimalarial to add to the armamentarium.

PMID- 28450629
TI  - A privileged status for animate objects.

PMID- 28450630
TI  - The making of the human brain.

PMID- 28450631
TI  - Planning for a rise.

PMID- 28450632
TI  - Menstrual cycle on a chip.

PMID- 28450633
TI  - Rise on the rise.

PMID- 28450634
TI  - Delaying demise.

PMID- 28450635
TI  - Virtues of splitting up water-splitting.

PMID- 28450638
TI  - Rechargeable nickel-3D zinc batteries: An energy-dense, safer alternative to
      lithium-ion.
AB  - The next generation of high-performance batteries should include alternative
      chemistries that are inherently safer to operate than nonaqueous lithium-based
      batteries. Aqueous zinc-based batteries can answer that challenge because
      monolithic zinc sponge anodes can be cycled in nickel-zinc alkaline cells
      hundreds to thousands of times without undergoing passivation or macroscale
      dendrite formation. We demonstrate that the three-dimensional (3D) zinc form
      factor elevates the performance of nickel-zinc alkaline cells in three fields of
      use: (i) >90% theoretical depth of discharge (DODZn) in primary (single-use)
      cells, (ii) >100 high-rate cycles at 40% DODZn at lithium-ion-commensurate
      specific energy, and (iii) the tens of thousands of power-demanding duty cycles
      required for start-stop microhybrid vehicles.

PMID- 28450639
TI  - Measurement of the small-scale structure of the intergalactic medium using close
      quasar pairs.
AB  - The distribution of diffuse gas in the intergalactic medium (IGM) imprints a
      series of hydrogen absorption lines on the spectra of distant background quasars
      known as the Lyman-alpha forest. Cosmological hydrodynamical simulations predict
      that IGM density fluctuations are suppressed below a characteristic scale where
      thermal pressure balances gravity. We measured this pressure-smoothing scale by
      quantifying absorption correlations in a sample of close quasar pairs. We
      compared our measurements to hydrodynamical simulations, where pressure smoothing
      is determined by the integrated thermal history of the IGM. Our findings are
      consistent with standard models for photoionization heating by the ultraviolet
      radiation backgrounds that reionized the universe.

PMID- 28450636
TI  - Pcdhalphac2 is required for axonal tiling and assembly of serotonergic
      circuitries in mice.
AB  - Serotonergic neurons project their axons pervasively throughout the brain and
      innervate various target fields in a space-filling manner, leading to tiled
      arrangements of their axon terminals to allow optimal allocation of serotonin
      among target neurons. Here we show that conditional deletion of the mouse
      protocadherin alpha (Pcdhalpha) gene cluster in serotonergic neurons disrupts
      local axonal tiling and global assembly of serotonergic circuitries and results
      in depression-like behaviors. Genetic dissection and expression profiling
      revealed that this role is specifically mediated by Pcdhalphac2, which is the
      only Pcdhalpha isoform expressed in serotonergic neurons. We conclude that, in
      contrast to neurite self-avoidance, which requires single-cell identity mediated
      by Pcdh diversity, a single cell-type identity mediated by the common C-type Pcdh
      isoform is required for axonal tiling and assembly of serotonergic circuitries.

PMID- 28450637
TI  - Multicluster Pcdh diversity is required for mouse olfactory neural circuit
      assembly.
AB  - The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded
      by three closely linked gene clusters (Pcdhalpha, Pcdhbeta, and Pcdhgamma). Here,
      we show that all three gene clusters functionally cooperate to provide individual
      mouse olfactory sensory neurons (OSNs) with the cell surface diversity required
      for their assembly into distinct glomeruli in the olfactory bulb. Although
      deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss
      of all three clusters (tricluster deletion) led to a severe axonal arborization
      defect and loss of self-avoidance. By contrast, when endogenous Pcdh diversity is
      overridden by the expression of a single-tricluster gene repertoire (alpha and
      beta and gamma), OSN axons fail to converge to form glomeruli, likely owing to
      contact-mediated repulsion between axons expressing identical combinations of
      Pcdh isoforms.

PMID- 28450640
TI  - Formation of matter-wave soliton trains by modulational instability.
AB  - Nonlinear systems can exhibit a rich set of dynamics that are inherently
      sensitive to their initial conditions. One such example is modulational
      instability, which is believed to be one of the most prevalent instabilities in
      nature. By exploiting a shallow zero-crossing of a Feshbach resonance, we
      characterize modulational instability and its role in the formation of matter
      wave soliton trains from a Bose-Einstein condensate. We examine the universal
      scaling laws exhibited by the system and, through real-time imaging, address a
      long-standing question of whether the solitons in trains are created with
      effectively repulsive nearest-neighbor interactions or rather evolve into such a
      structure.

PMID- 28450641
TI  - A multifunctional catalyst that stereoselectively assembles prodrugs.
AB  - The catalytic stereoselective synthesis of compounds with chiral phosphorus
      centers remains an unsolved problem. State-of-the-art methods rely on resolution
      or stoichiometric chiral auxiliaries. Phosphoramidate prodrugs are a critical
      component of pronucleotide (ProTide) therapies used in the treatment of viral
      disease and cancer. Here we describe the development of a catalytic
      stereoselective method for the installation of phosphorus-stereogenic
      phosphoramidates to nucleosides through a dynamic stereoselective process.
      Detailed mechanistic studies and computational modeling led to the rational
      design of a multifunctional catalyst that enables stereoselectivity as high as
      99:1.

PMID- 28450642
TI  - Direction-specific van der Waals attraction between rutile TiO2 nanocrystals.
AB  - Mutual lattice orientations dictate the types and magnitudes of forces between
      crystalline particles. When lattice polarizability is anisotropic, the van der
      Waals dispersion attraction can, in principle, contribute to this direction
      dependence. We report measurement of this attraction between rutile nanocrystals,
      as a function of their mutual orientation and surface hydration extent. At tens
      of nanometers of separation, the attraction is weak and shows no dependence on
      azimuthal alignment or surface hydration. At separations of approximately one
      hydration layer, the attraction is strongly dependent on azimuthal alignment and
      systematically decreases as intervening water density increases. Measured forces
      closely agree with predictions from Lifshitz theory and show that dispersion
      forces can generate a torque between particles interacting in solution and
      between grains in materials.

PMID- 28450645
TI  - Standing up to fear.

PMID- 28450643
TI  - Ancient genomic changes associated with domestication of the horse.
AB  - The genomic changes underlying both early and late stages of horse domestication
      remain largely unknown. We examined the genomes of 14 early domestic horses from
      the Bronze and Iron Ages, dating to between ~4.1 and 2.3 thousand years before
      present. We find early domestication selection patterns supporting the neural
      crest hypothesis, which provides a unified developmental origin for common
      domestic traits. Within the past 2.3 thousand years, horses lost genetic
      diversity and archaic DNA tracts introgressed from a now-extinct lineage. They
      accumulated deleterious mutations later than expected under the cost-of
      domestication hypothesis, probably because of breeding from limited numbers of
      stallions. We also reveal that Iron Age Scythian steppe nomads implemented
      breeding strategies involving no detectable inbreeding and selection for coat
      color variation and robust forelimbs.

PMID- 28450647
TI  - Translation and Adaptation of Foreign Questionnaire: The First Step Should be
      Done Before Used.

PMID- 28450646
TI  - Effect of mitotane on mouse ovarian follicle development and fertility.
AB  - Mitotane (MTT) is an adrenolytic drug used in advanced and adjuvant treatment of
      adrenocortical carcinoma, in Cushing's disease and in ectopic syndrome. However,
      knowledge about its effects on the ovary is still scarce. The purpose of this
      study is to investigate the effect of MTT on the ovary using in vivo and in vitro
      models. The study was performed in CD1 mice and in the COV-434 human ovarian
      granulosa cell line. We examined ovarian morphology, follicle development,
      steroidogenesis and procreative function in mice and the effect of MTT on cell
      growth in vitro Our results revealed that treatment of CD1 mice with MTT induces
      a decrease in early antral follicles with a subsequent increase in the secondary
      follicles, measured by the increased levels of anti-Mullerian Hormone (P < 0.05)
      and decreased levels of FSH receptor (P < 0.05). Moreover, we observed a
      significant decrease in Cyp11a1 (P < 0.01) and Cyp17a1 (P < 0.001) mRNA level in
      MTT-treated animals. Ovulation, induced by PMSG/hCG stimulation, was also
      significantly impaired, with a reduction in the number of ovulated oocytes (P <
      0.01) and fewer corpora lutea in treated animals. Likewise, the mating experiment
      demonstrated a delay in the time of conception as well as fewer pups per litter
      in MTT-treated mice (P < 0.05). Experiments performed on the COV-434 cell line
      showed a significant inhibition of growth followed by apoptosis (P < 0.01). In
      conclusion, our study highlights the key points of ovarian folliculogenesis
      affected by MTT and demonstrates impairment of the ovulation process with a
      negative impact on conception, which is nevertheless preserved.

PMID- 28450648
TI  - The Validity and Reliability Test of the Indonesian Version of Gastroesophageal
      Reflux Disease Quality of Life (GERD-QOL) Questionnaire.
AB  - AIM: to obtain a valid and reliable GERD-QOL questionnaire for Indonesian
      application. METHODS: at the initial stage, the GERD-QOL questionnaire was first
      translated into Indonesian language and the translated questionnaire was
      subsequently translated back into the original language (back-to-back
      translation). The results were evaluated by the researcher team and therefore, an
      Indonesian version of GERD-QOL questionnaire was developed. Ninety-one patients
      who had been clinically diagnosed with GERD based on the Montreal criteria were
      interviewed using the Indonesian version of GERD-QOL questionnaire and the SF 36
      questionnaire. The validity was evaluated using a method of construct validity
      and external validity, and reliability can be tested by the method of internal
      consistency and test retest. RESULTS: the Indonesian version of GERD-QOL
      questionnaire had a good internal consistency reliability with a Cronbach Alpha
      of 0.687-0.842 and a good test retest reliability with an intra-class correlation
      coefficient of 0.756-0.936; p<0.05). The questionnaire had also been demonstrated
      to have a good validity with a proven high correlation to each question of SF-36
      (p<0.05). CONCLUSION: the Indonesian version of GERD-QOL questionnaire has been
      proven valid and reliable to evaluate the quality of life of GERD patients.

PMID- 28450649
TI  - Validity and Reliability of the Indonesian Version of SF-36 Quality of Life
      Questionnaire on Patients with Permanent Pacemakers.
AB  - AIM: to construct and validate Indonesian version of SF-36. METHODS: this is a
      cross-sectional study, which consist of 2 stages process: 1) language and
      cultural adaption; and 2) validity and reliability evaluation. We evaluated 32
      pacemaker patients during language and cultural adaptation stage and 20 pacemaker
      patients during validity and reliability evaluation stages from September 2014 to
      August 2015. We followed cross-cultural adaptation guideline to produce
      Indonesian version of the questionnaire. The final translated questionnaire was
      checked by assessing the correlation of SF-36 and 6-minutes walking test (6MWT)
      and NT pro-BNP result. RESULTS: Indonesian version of SF-36 showed positive
      correlation between 6MWT result and physical functioning (PF) (r=0.363; p=0.001)
      and negative correlation between NT pro-BNP score with general health (GH) (r=
      0.269; p=0.020) and mental health (MH) (r=-0.271; p=0.019). The internal
      consistency of Indonesian version of SF-36 questionnaire, which measured by
      Cronbach's alpha, was good with value of >0.70. Repeatability between day 1 and
      day 8 was good, with strong positive correlation (r=0.626; p=0.003). CONCLUSION:
      the Indonesian version of SF-36 could be used as a general questionnaire to
      assess quality of life in patients with permanent pacemaker.

PMID- 28450650
TI  - Y-Chromosomal Microdeletion in Idiopathic Azoospermic and Severe Oligozoospermic
      Indonesian Men.
AB  - AIM: to detect Y-chromosomal microdeletion in Indonesian men with azoospermia or
      severe oligozoospermia using multiplex PCR. METHODS: we performed 2 multiplex PCR
      amplifications of the Azoospermia Factor (AZF) region in 71 men. Criteria for
      including a patient were fulfilled if they presented with azoospermia or severe
      oligozoospermia, with or without additional abnormalities of sperm motility or of
      head morphology, raised or normal levels of FSH, normal levels of LH and
      testosterone, and with no evidence of testicular tumors or other abnormalities.
      Five men participated as control persons. RESULTS: partial deletion of AZFa was
      found in 11 men (15.49%), complete deletion of AZFb in 1 man (1.4%), and complete
      deletion of AZFc in 1 man (1.4%). The unspecific type of deletion was also
      detected, including the DBY gene in 2 men (2.81%), and partial deletion of both
      AZFa and AZFb in 2 men (2.81%). No AZF deletion was observed in the control
      probands. Related to the type of deletion, the AZFa and AZFb deletion showed
      spermatogenesis arrest in most tubules, while deletion of the DBY gene is
      associated with the sertoli cell only (SCO) syndrome. CONCLUSION: the frequency
      of partial deletion of AZFa was found to be relatively high in our center. The
      type of deletion is associated with the testicular histology.

PMID- 28450651
TI  - The Immunogenicity and Safety of CYD-Tetravalent Dengue Vaccine (CYD-TDV) in
      Children and Adolescents: A Systematic Review.
AB  - AIM: to assess the immunogenicity and safety of CYD-tetravalent dengue vaccine
      (CYD-TDV) in children. METHODS: comprehensive literature searches were conducted
      on various databases. Randomized-controlled trials on children with CYD-TDV as
      intervention were selected based on inclusion and exclusion criteria. Data
      extracted from selected trials included safety of vaccine and immunogenicity in
      terms of Geometric Mean Titres (GMT) of antibodies. RESULTS:   six clinical
      trials were selected based on preset criteria. GMT values were obtained using 50%
      Plaque Reduction Neutralization Test (PRNT) and safety was semi-quantitatively
      assessed based on adverse effects. Additional data processing was done to obtain
      a better understanding on the trends among the studies. The results showed that
      the groups vaccinated with CYD-TDV showed higher immunogenicity against dengue
      virus antigens than the control groups. Safety results were satisfactory in all
      trials, and most severe side effects were unrelated to the vaccine. CONCLUSION:
      CYD-TDV is both effective and safe for patients in endemic regions. This gives
      promise for further development and large-scale research on this vaccine to
      assess its efficacy in decreasing dengue prevalence, and its pervasive
      implementation in endemic countries, such as Indonesia.

PMID- 28450652
TI  - Concordance between Reticulocyte Hemoglobin Equivalent and Reticulocyte
      Hemoglobin Content in CKD Patients Undergoing Hemodialysis.
AB  - AIM: to evaluate the correlation and the concordance between reticulocyte
      hemoglobin equivalent (RET-He) and reticulocyte hemoglobin content (CHr) as well
      as to obtain the cut-off value of RET-He as the target of iron supplementation in
      chronic kidney disease (CKD) patients undergoing hemodialysis. METHODS: a cross
      sectional study was performed using K3EDTA-anticoagulated peripheral blood
      samples collected from 106 CKD patients undergoing routine hemodialysis. The
      samples were then analyzed using both Sysmex XN-2000 and Siemens ADVIA 2120i for
      RET-He and CHr analysis. RESULTS: a very strong correlation (r=0.91; p<0.0001)
      and a good concordance were found between RET-He and CHr with mean bias of 0.5
      pg. The diagnostic concordance was 96.23%. The cut-off value of RET-He 29.2 pg
      was obtained from the receiver operating characteristic (ROC) curve with CHr as
      the gold standard. At this cut-off point, the sensitivity and specificity to
      assess the target of iron supplementation in CKD patients undergoing hemodialysis
      were 95.5% and 94%, respectively. CONCLUSION: the study shows a good correlation
      and concordance between RET-He and CHr in CKD patients undergoing hemodialysis.

PMID- 28450653
TI  - Prediction of Wound Healing in Diabetic Foot Ulcers: an Observational Study in
      Tertiary Hospital in Indonesia.
AB  - AIM: to evaluate the role of clinical characteristics, functional markers of
      vasodilation, inflammatory response, and atherosclerosis in predicting wound
      healing in diabetic foot ulcer. METHODS: a cohort study (February - October 2010)
      was conducted from 40 subjects with acute diabetic foot ulcer at clinical ward of
      Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia.
      Each subject underwent at least two variable measurements, i.e. during
      inflammatory phase and proliferation phase. The studied variables were clinical
      characteristics, complete peripheral blood count (CBC) and differential count,
      levels of HbA1c, ureum, creatinine, lipid profile, fasting blood glucose (FBG),
      marker of endothelial dysfunction (asymmetric dimethylarginine/ADMA, endothelin
      1/ET-1, and flow-mediated dilation/FMD of brachial artery), and marker of
      vascular calcification (osteoprotegerin/OPG). RESULTS: median of time achieving
      50% granulation tissue in our study was 21 days. There were nine factors that
      contribute in the development of 50% granulation tissue, i.e. family history of
      diabetes mellitus (DM), previous history of wound, wound area, duration of
      existing wound, captopril and simvastatin medications, levels of ADMA, ET-1, and
      OPG. There were three out of the nine factors that significantly correlated with
      wound healing, i.e. wound area, OPG levels, and simvastatin medications.
      CONCLUSION: in acute diabetic foot ulcers, wound area and OPG levels had positive
      correlation with wound healing, whereas simvastatin medications had negative
      correlation with wound healing.

PMID- 28450654
TI  - Left Circumflexus Coronary Artery Total Occlusion with Clinical Presentation as
      NSTEMI and Acute Pulmonary Oedema.
AB  - Current guidelines for the management of patients with acute coronary syndromes
      (ACSs) focus on the electrocardiogram to divide patients into ST-elevation acute
      myocardial infarction (STEMI) or non-ST-elevation acute myocardial infarction
      (NSTEMI)/unstable angina (UA). Patients with STEMI in the earliest time will
      receive reperfusion therapy to destruct occlusive thrombus. An ST segment
      elevation is the 'sine qua non' for diagnosing acute total coronary occlusion
      causing transmural myocardial infarction. Left circumflex coronary artery (LCx)
      occlusion is often categorized as NSTEMI because of the absence of significant ST
      elevation on the 12 lead standard electrocardiogram. An ST segment elevation is
      presented in fewer than 50% of patients with LCx total occlusion, such that the
      reperfusion therapy is delayed. We reported a 77 years old woman whom being
      diagnosed with NSTEMI because a 12 lead electrocardiogram showed ST segment
      depression in lead V2-V5. On coronary angiography, we found a total occlusion in
      the LCx artery as the culprit lession.

PMID- 28450655
TI  - Riedel's Lobe: Clinical Importance of a Rare Variant in Liver Morphology.
AB  - Riedel's lobe is a normal variant form of right liver lobe rarely found. Here we
      report a case of 38 years old female with an incidental finding not revealed in
      physical examination, but then known to have hepatomegaly by gynecological
      ultrasonography. Diagnosis of Riedel's lobe was strengthened by similar results
      on hepatobiliary ultrasonography, abdominal MRI, and diagnostic laparoscopy. Our
      patient was discharged and had follow up examination three months later.
      Knowledge regarding this anomaly is essential to be understood because the
      finding of accessory liver lobe does not always remain asymptomatic as in our
      patient, but rather can be related to significant clinical complication.

PMID- 28450656
TI  - Regulatory T Cell Immunity in Atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disorder involving innate and adaptive
      immunity process. Effector T cell (Teff) responses promote atherosclerotic
      disease, whereas regulatory T cells (Tregs) have been shown to play a protective
      role against atherosclerosis by down-regulating inflammatory responses which
      include multiple mechanisms. Compelling experimental data suggest that shifting
      the Treg/Teff balance toward Tregs may be a possible therapeutic approach for
      atherosclerotic disease, although the role of Tregs in human atherosclerotic
      disease has not been fully elucidated. In this review, we discuss recent advances
      in our understanding of the roles of Tregs and Teffs in experimental
      atherosclerosis, as well as human coronary artery disease.

PMID- 28450657
TI  - Parathyroid Adenoma in a Young Female Presenting Multiple Fractures and
      Postoperative Hungry Bone Syndrome.
AB  - A young 18-year-old female patient with general bone pain and history of multiple
      fractures brought her to our medical attention. Laboratory work showed
      hypercalcemia and high parathyroid hormone levels in the blood. Radiograph
      imaging revealed severe scoliosis with multiple vertebrae fractures with
      decreased bone mineral density. Sestamibi showed parathyroid adenoma. This case
      emphasizes the importance of maintaining a primary hyperparathyroidism as a
      differential diagnosis when a young patient presents with a multiple pathologic
      fractures history.

PMID- 28450658
TI  - The Role of Docetaxel in Non-Castrate Resistant Metastatic Prostate Cancer: An
      Evidence-based Case Report.
AB  - AIM: to learn the role of docetaxel in non-castrate resistant prostate cancer
      patient. METHODS: literature search was conducted to find relevant study
      comparing the combination of docetaxel and androgen deprivation therapy (ADT) to
      ADT alone in non-castrate resistant prostate cancer using PubMed, Cohrane
      Library, Proquest, EBSCO, and Scopus database. Quality assessment of studies was
      done using Bond University Rapid Critical Appraisal of a Systematic Review.
      RESULTS: we found 494 studies from literature search, but only two studies were
      included in final selection. Based on validity assessment, we chose one study to
      be discussed further. This study showed that combination of docetaxel and ADT is
      better than ADT alone in regards of overall survival (HR 0.64; 95% CI 0.55, 0.75;
      p<0.0001; NNT=3), biochemical progression free survival (HR 0.63; 95% CI 0.57,
      0.69; p<0.0001; NNT=2) and clinical progression free survival (HR 0.73; 95% CI
      0.64, 0.84; p<0.0001; NNT=2). Benefit of docetaxel and ADT combination was
      especially seen in high volume disease (HR 0.67; 95% CI 0.54, 0.83; p=0.0003;
      NNT=3). CONCLUSION: addition of docetaxel into ADT has beneficial effects in
      terms of overall survival and progression free survival in patients with non
      castrate resistant metastatic prostate cancer.

PMID- 28450659
TI  - Recent Management of Patients with Advanced Epidermal Growth Factor Receptor
      Mutation Non-small Cell Lung Cancer: Role of Afatinib and Lesson Learned for
      Developing Countries.
AB  - Lung cancer is a devastating disease with a high incidence, mortality and
      morbidity rate, especially in developing countries. Conventional treatment with
      cytotoxic chemotherapy has some limitations attributed to chemoresistance and
      toxicity. Recent advances have shown that first generation Tyrosine Kinase
      Inhibitor (TKI), Gefitinib and Erlotinib, and the newest available second
      generation Tyrosine Kinase Inhibitor (TKI), Afatinib, have the potential to be an
      option in the management of patients with epidermal growth factor receptor/ EGFR
      mutation positive advanced/ metastatic non-small cell lung cancer. Afatinib works
      by binding to EGFR irreversibly, thus inactivating the tyrosine kinase receptor.
      Some studies demostrated that Afatinib first-line may result in longer
      progression free survival (PFS) and better disease control, and as an alternative
      for patients who intolerance to Gefitinib or Erlotinib. In Indonesia, the era of
      National Health Insurance has been implemented and National Health Insurance has
      covered treatment for cancer, including first generation TKIs, Gefitinib dan
      erlotinib, for patients with EGFR mutation positive advanced/ metastatic non
      small cell lung cancer at Cipto Mangunkusumo National Hospital. Afatinib, as one
      of the newest available second generation TKI, may be given free of charge too as
      an alternative if the National Health Insurance will be covered in the future.
      Further research is needed to know the efficacy and adverse effects that may
      occur in patients from developing countries.

PMID- 28450660
TI  - Understory Dwarf Bamboo Affects Microbial Community Structures and Soil
      Properties in a Betula ermanii Forest in Northern Japan.
AB  - In order to understand the relationships between understory bamboo and soil
      properties, we compared microbial community structures in the soil of a Betula
      ermanii boreal forest with Sasa kurilensis present and removed using high
      throughput DNA sequencing. The presence of understory S. kurilensis strongly
      affected soil properties, including total carbon, total nitrogen, nitrate, and
      the C:N ratio as well as relative soil moisture. Marked differences were also
      noted in fungal and bacterial communities between plots. The relative abundance
      of the fungal phylum Ascomycota was 13.9% in the Sasa-intact plot and only 0.54%
      in the Sasa-removed plot. Among the Ascomycota fungi identified, the most
      prevalent were members of the family Pezizaceae. We found that the abundance of
      Pezizaceae, known to act as mycorrhizal fungi, was related to the amount of total
      carbon in the Sasa-intact plot. The relative abundance of Proteobacteria was
      significantly higher, whereas those of Planctomycetes and Actinobacteria were
      lower in the Sasa-intact plot than in the Sasa-removed plot. Furthermore, the
      results obtained suggest that some species of the phylum Planctomycetes are more
      likely to occur in the presence of S. kurilensis. Collectively, these results
      indicate that the presence of S. kurilensis affects microbial communities and
      soil properties in a B. ermanii boreal forest.

PMID- 28450661
TI  - Prevalence and molecular characterization of extended-spectrum beta-lactamase
      (ESBL) and plasmidic AmpC beta-lactamase (pAmpC) producing Escherichia coli in
      dogs.
AB  - This study aimed to determine the prevalence of fecal carriage of extended
      spectrum beta-lactamase (ESBL) and/or plasmidic AmpC beta-lactamase (pAmpC)
      producing Escherichia coli among dogs (n=428) in Turkey. Polymerase chain
      reaction (PCR) and sequencing were used to characterize genes encoding beta
      lactamase and plasmid mediated quinolone resistance (PMQR). Antimicrobial
      susceptibility testing and PCRs for virulence genes and phylogenetic groups were
      also performed. Cefotaxime resistant E. coli isolates were detected in 95 (22.2%)
      of the swab samples. Sequencing analysis results showed occurrence of various
      beta-lactamase genes: blaCTX-M-15 (62), blaTEM-1b (42), blaCMY-2 (22), blaCTX-M-3
      (16), blaCTX-M-1 (15), blaOXA-1 (9) and blaSHV-12 (3) alone or in combination.
      The most frequently encountered phylogenetic group was group A1 (35.8%), followed
      by group D2 (22.1%), B1 (15.8%), D1 (9.5%), A0 (7.4%), B22 (5.3%) and B23 (4.2%),
      respectively. PMQR genes, aac(6')-Ib-cr, qnrS1 and qnrB10 were detected in 25.3,
      10.5 and 1.1% of the isolates, respectively. While all isolates were susceptible
      to imipenem and amikacin, resistance rates to non-beta-lactam antibiotics ranged
      from 20.0% for tobramycin to 56.8% for tetracycline. The virulence genes were
      only detected in 34 (36.2%) of the isolates and this isolates carried single or
      various combination of virulence genes of iucD, papC, papE, f17a-A and eaeA. Four
      isolates were identified as human virulent pandemic CTX-M-15 producing E. coli
      clone O25b:ST131/B2. To the best of our knowledge, this is the first study to
      show fecal carriage of ESBL/pAmpC type beta-lactamase producing E. coli isolates
      among dogs in Turkey.

PMID- 28450662
TI  - Comparative serological investigation between cat and tiger blood for
      transfusion.
AB  - Evidence suggests that non-domesticated felids inherited the same AB-erythrocyte
      antigens as domestic cats. To study the possible compatibility of tiger blood
      with that of other endangered felidae, blood samples from captive tigers and
      domestic cats were subjected to an in vitro study. The objectives of this study
      were to (1) identify whether the captive tigers had blood type AB and (2)
      determine the compatibility between the blood of captive tigers and that of
      domestic cats with a similar blood type. The anti-coagulated blood with
      ethylenediaminetetraacetic acid of 30 tigers was examined to determine blood
      type, and a crossmatching test was performed between tiger and cat blood. All 30
      tigers had blood type A. Tube agglutination tests using tiger plasma with cat
      erythrocytes resulted in 100% agglutination (n=30) with type B cat erythrocytes
      and 76.7% agglutination (n=23) with type A cat erythrocytes. The 80% of major and
      60% of minor compatibilities between blood from 10 tigers and 10 domestic cats
      with blood type A were found to pass compatibility tests. Interestingly, 3/10 of
      the tigers' red blood cell samples were fully compatible with all cat plasmas,
      and 1/10 of the tiger plasma samples were fully compatible with the type A red
      cells of domestic cats. Although the result of present findings revealed type-A
      blood group in the surveyed tigers, the reaction of tiger plasma with Type-A red
      cell from cats suggested a possibility of other blood type in tigers.

PMID- 28450663
TI  - Epidemiology of Myocardial Infarction Caused by Presumed Paradoxical Embolism via
      a Patent Foramen Ovale.
AB  - BACKGROUND: Despite several negative prospective randomized trials on the
      efficacy of patent foramen ovale (PFO) occlusion, the discussion on indications
      is ongoing. Because the incidence of paradoxical coronary embolism through a PFO
      is unknown, we investigated the risk of paradoxical embolic myocardial infarction
      over a period of 13 years.Methods and Results:We conducted a retrospective and a
      prospective study. In the former, we searched the hospital database of a tertiary
      referral center for cases of acute myocardial infarction (AMI) during the past 10
      years and screened them for possible paradoxical MIs. On this basis we started a
      prospective evaluation over 39 months in another tertiary referral center. All
      patients with AMI and normal coronary arteries were screened for PFO and if no
      other reason for the AMI could be found, the case was judged as presumed
      paradoxical embolism. In the retrospective analysis we found 22 cases (0.45%) of
      presumed paradoxical coronary artery embolism under 4,848 AMI. In the prospective
      study there were 11 presumed paradoxical coronary artery embolisms among 1,654
      patients with AMI, representing an incidence of 0.67%. CONCLUSIONS: Our findings
      demonstrated that well below 1% of AMIs are caused by paradoxical embolism via an
      interatrial communication. Although this percentage appears low, it is not a
      negligible number of patients based on the huge number of MIs occurring in the
      industrialized world.

PMID- 28450664
TI  - Report of the Annual Scientific Sessions of the American College of Cardiology
      (ACC), Washington DC.
AB  - The 66thAnnual Scientific Sessions and Expo of the American College of Cardiology
      (ACC) were held at the Walter E. Washington Convention Center, Washington DC,
      from March 17thto 19th, 2017. This meeting offered 23 Late-Breaking Clinical
      Trial (LBCT) presentations, 17 Featured Clinical Research presentations with and
      without LBCT, and 2,572 abstracts presented in oral and poster sessions by over
      2,000 experts. This report presents the highlights of this meeting, including the
      opening showcase, several important LBCTs and some international joint
      symposiums.

PMID- 28450665
TI  - Early diagnosis of chronic pancreatitis: understanding the factors associated
      with the development of chronic pancreatitis.
AB  - The prognosis of advanced chronic pancreatitis (CP) is poor with the mortality
      rate approximately two-fold higher than the general population according to a
      survey of the prognosis of CP. From this standpoint, the concept of early CP was
      propagated in Japan in 2009 to encourage the medical treatment for the earlier
      stages of CP. That is, picking up the patients suspicious for early CP and then
      providing medical treatment for them are very important not only for patients,
      but also for health care economics. In this review, we described some potential
      factors associated with the development of CP (alcohol, smoking, past history of
      acute pancreatitis, aging, gallstone, and gender) that are extremely important to
      discover patients with early-stage CP.

PMID- 28450666
TI  - Anomalies of the Middle Cerebral Artery.
AB  - There are several anomalies of the middle cerebral artery (MCA) in humans, such
      as accessory MCA, duplicated MCA, fenestration of MCA, and duplicated origin of
      MCA. Recently, unfused or twig-like MCA, which indicates MCA trunk occlusion with
      collateral plexiform arterial network, have been reported. During the embryonic
      stage, MCA is thought to generate from plexiform arterial twigs arising from the
      anterior cerebral artery, and these twigs form the definitive MCA by fusion and
      regression at the end of the development stage. Any interruption during the
      fusion of the arterial twigs may result in MCA anomalies, and the unfused or twig
      like MCA, especially, is hypothesized to be the persistent primitive arterial
      twigs. Clinically, it is challenging to differentiate the unfused or twig-like
      MCA from unilateral moyamoya disease, in which stenotic change begins at the MCA.
      The knowledge of the anomalies of the MCA is important to perform a safe surgical
      or endovascular intervention.

PMID- 28450667
TI  - One-Year Outcome of Fractional Flow Reserve-Based Coronary Intervention in
      Japanese Daily Practice - CVIT-DEFER Registry.
AB  - BACKGROUND: Clinical use of fractional flow reserve (FFR) has been rapidly
      increasing, but outcomes after FFR-based coronary intervention in Japanese daily
      clinical practice have not been well investigated.Methods and Results:The
      prospective multicenter cardiovascular intervention therapeutics registry (CVIT)
      DEFER enrolled consecutive patients for whom FFR measurement was clinically
      indicated. This study comprised 3,857 vessels in 3,272 patients. Lesions were
      categorized into 4 groups according to FFR result and revascularization strategy:
      group 1: FFR >0.8, and deferral of PCI (n=1992); group 2: FFR >0.8, then PCI
      (n=230); group 3: FFR <=0.8, and deferral of PCI (n=506); and group 4: FFR <=0.8,
      then PCI (n=1,129). The event rate for deferred lesions was significantly low
      compared with that for PCI lesions (3.5% vs. 6.6%; P<0.05). Vessel-related events
      occurred in 62 (3.1%), 11 (4.8%), 25 (4.9%), and 79 (7.0%) patients in groups 1,
      2, 3, and 4, respectively. PCI for lesions in which FFR was >0.8 (group 2) showed
      no improvement in the event rate compared with a defer-strategy. On the other
      hand, deferred lesions with lower FFR values had a higher risk of vessel-related
      events. CONCLUSIONS: A FFR-based revascularization strategy in daily clinical
      practice was safe with regard to vessel-related events.

PMID- 28450668
TI  - Impact of Surgery in Ebstein's Anomaly Using Current Surgical Criteria.
AB  - BACKGROUND: In Ebstein's anomaly (EA) current surgical criteria may not translate
      into better long-term survival. The aim of this study was therefore to determine
      if surgical treatment for EA increases survival, and to analyze factors
      associated with mortality.Methods and Results:A retrospective study was carried
      out involving 103 patients with surgical indication using current criteria,
      comparing operated (n=49; 47.5%) and non-operated patients (n=54; 52.4%); the
      severity of disease was similar in all cases. Overall follow-up was 12 years
      (range, 1-49 years). There were no differences in mortality: in the surgical and
      non-surgical groups, survival at 10 years was 92.8% vs. 90.7%; 20 years, 85.7%
      vs. 81.0%; and 30 years, 78.5% vs. 72.2%, respectively. On multivariate analysis
      right ventricular fractional shortening (RVFS) was associated with mortality in
      both groups. Decreasing RVFS was associated with worse survival according to
      severity: when RVFS was <20%, survival at 20, 40 and 60 years was 58%, 39%, and
      12.5%, respectively (P<0.0013). Left ventricular ejection fraction also
      correlated with survival (P<0.0013). CONCLUSIONS: Surgery did not translate into
      benefit in terms of survival, and this was clearly associated with RV function;
      therefore this should be a key factor in the surgical decision making.

PMID- 28450669
TI  - Comparison of Prognostic Values of Daytime and Night-Time Systolic Blood
      Pressures on Renal Outcomes in Patients With Chronic Kidney Disease.
AB  - BACKGROUND: Differences in the predictive value of daytime systolic blood
      pressure (SBP) and night-time SBP by ambulatory blood pressure monitoring on
      renal outcomes have not been fully investigated in chronic kidney disease (CKD)
      patients. This study compared the prognostic value between daytime and night-time
      SBP on renal outcomes in CKD.Methods and Results:This prospective observational
      study included 421 patients. The composite renal endpoint was endstage renal
      disease (ESRD) or death. Cox models were used to determine associations of
      daytime and night-time SBP with renal outcomes. There were 150 renal events
      (ESRD, 130; death, 20). Multivariable Cox analyses demonstrated that hazard
      ratios (HRs) [95% confidence interval (CI)] for composite renal outcomes of every
      10-mmHg increase in daytime and night-time SBP levels were 1.13 (1.02-1.26)
      (P=0.02) and 1.15 (1.05-1.27) (P<0.01), respectively. In addition, compared with
      the 1st daytime or night-time SBP quartile, HRs (95% CI) for outcomes in the 2nd,
      3rd, and 4th quartiles were: daytime SBP, 1.25 (0.70-2.25), 1.09 (0.61-1.94), and
      1.58 (0.88-2.85; P=0.13) (P for trend=0.16); night-time SBP, 1.09 (0.61-1.96),
      1.31 (0.76-2.28), and 1.82 (1.00-3.30; P=0.049) (P for trend=0.03), respectively.
      CONCLUSIONS: Night-time SBP appeared superior to daytime SBP for predicting renal
      outcomes in this population of patients.

PMID- 28450670
TI  - Gamma-Glutamyl Transferase as a Risk Biomarker of Cardiovascular Disease - Does
      It Have Another Face?

PMID- 28450671
TI  - Effect of cavity disinfectants on antibacterial activity and microtensile bond
      strength in class I cavity.
AB  - This study was performed to compare the antibacterial activities of three cavity
      disinfectants [chlorhexidine (CHX), NaOCl, urushiol] and to evaluate their effect
      on the microtensile bond strength of Scotchbond Universal Adhesive (3M-ESPE, St.
      Paul, MN, USA) in class I cavities. In both experiments, class I cavities were
      prepared in dentin. After inoculation with Streptococcus mutans, the cavities of
      control group were rinsed and those of CHX, NaOCl and urushiol groups were
      treated with each disinfectant. Standardized amounts of dentin chips were
      collected and number of S. mutans was determined. Following the same cavity
      treatment, same adhesive was applied in etch-and-rinse mode. Then, microtensile
      bond strength was evaluated. The number of S. mutans was significantly reduced in
      the cavities treated with CHX, NaOCl, and urushiol compared with control group
      (p<0.05). However, there was a significant bond strength reduction in NaOCl
      group, which showed statistical difference compared to the other groups (p<0.05).

PMID- 28450672
TI  - Dose effects of beta-tricalcium phosphate nanoparticles on biocompatibility and
      bone conductive ability of three-dimensional collagen scaffolds.
AB  - Three-dimensional collagen scaffolds coated with beta-tricalcium phosphate (beta
      TCP) nanoparticles reportedly exhibit good bioactivity and biodegradability. Dose
      effects of beta-TCP nanoparticles on biocompatibility and bone forming ability
      were then examined. Collagen scaffold was applied with 1, 5, 10, and 25 wt% beta
      TCP nanoparticle dispersion and designated TCP1, TCP5, TCP10, and TCP25,
      respectively. Compressive strength, calcium ion release and enzyme resistance of
      scaffolds with beta-TCP nanoparticles applied increased with beta-TCP dose. TCP5
      showed excellent cell-ingrowth behavior in rat subcutaneous tissue. When TCP10
      was applied, osteoblastic cell proliferation and rat cranial bone augmentation
      were greater than for any other scaffold. The bone area of TCP10 was 7.7-fold
      greater than that of non-treated scaffold. In contrast, TCP25 consistently
      exhibited adverse biological effects. These results suggest that the application
      dose of beta-TCP nanoparticles affects the scaffold bioproperties; consequently,
      the bone conductive ability of TCP10 was remarkable.

PMID- 28450673
TI  - Effect of long-time immersion of soft denture liners in water on viscoelastic
      properties.
AB  - Aim of this study was to investigate the effect of long-time immersion of soft
      denture liners in 37 degrees C water on viscoelastic properties. Six silicone
      based and two acrylic resin-based soft denture liners were selected. Cylindrical
      specimens were stored in distilled water at 37 degrees C for 6 months.
      Viscoelastic properties, which were instantaneous and delayed elastic
      displacements, viscous flow, and residual displacement, were determined using a
      creep meter, and analyzed with 2-way analysis of variance and Tukey's comparison
      (alpha=0.05). Viscoelastic properties and their time-dependent changes were
      varied among materials examined. The observed viscoelastic properties of three
      from six silicone-based liners did not significantly change after 6-month
      immersion, but those of two acrylic resin-based liners significantly changed with
      the increase of immersion time. However, the sum of initial instantaneous elastic
      displacement and delayed elastic displacement of two acrylic resin-based liners
      during 6-month immersion changed less than 10%, which might indicate clinically
      sufficient elastic performance.

PMID- 28450674
TI  - Effects of powder-to-liquid ratio on properties of beta-tricalcium-phosphate
      cements modified using high-energy ball-milling.
AB  - The authors have developed a beta-tricalcium-phosphate (beta-TCP) powder modified
      mechano-chemically through the application of a ball-milling process (mbeta-TCP).
      The resulting powder can be used in a calcium-phosphate-cement (CPC). In this
      study, the effects of the powder-to-liquid ratio (P/L ratio) on the properties of
      the CPCs were investigated, and an appropriate P/L ratio that would
      simultaneously improve injectability and strength was clarified. The mbeta-TCP
      cement mixed at a P/L ratio of 2.5 and set in air exhibited sufficient
      injectability until 20 min after mixing, and strength similar to or higher than
      that mixed at a P/L ratio of 2.0 and 2.78. Although the mbeta-TCP cements set in
      vivo and in SBF were found to exhibit a lower strength than those set in air, it
      did have an appropriate setting time and strength for clinical applications. In
      conclusion, P/L ratio optimization successfully improved the strength of
      injectable mbeta-TCP cement.

PMID- 28450675
TI  - The effect of heat treatments applied to superstructure porcelain on the
      mechanical properties and microstructure of lithium disilicate glass ceramics.
AB  - The aim of this study was to investigate that heat treatments with different
      numbers applied to superstructure porcelain whether effects microstructure and
      mechanical properties of lithium disilicate ceramic (LDC). Eighty disc-shaped
      specimens were fabricated from IPS e.max Press. Specimens were fired at heating
      values of porcelain in different numbers and divided four groups (n=5). Initial
      Vickers hardness were measured and X-ray diffraction (XRD) analysis was
      performed. Different surface treatment were applied and then Vickers hardness,
      surface roughness and environmental scanning electron microscopy (ESEM) analysis
      were performed. Data were analyzed with Varyans analysis and Tukey HSD test
      (alpha=0.05). Initial hardness among groups was no significant different
      (p>0.05), but hardness and surface roughness after surface treatments were
      significant different (p<0.05). Lithium disilicate (LD) peaks decrease depended
      on firing numbers. ESEM observations showed that firing number and surface
      treatments effect microstructure of LDC. Increasing firing numbers and surface
      treatments effect the microstructure of LDC.

PMID- 28450676
TI  - Predictors of Recurrent In-Stent Restenosis After Paclitaxel-Coated Balloon
      Angioplasty.
AB  - BACKGROUND: Although paclitaxel-coated balloon (PCB) angioplasty is an effective
      procedure for in-stent restenosis (ISR) after coronary stenting, recurrent ISR
      after PCB angioplasty still occurs. The aim of this study was to evaluate the
      predictors of recurrent ISR after PCB angioplasty for ISR.Methods and Results:A
      total of 157 ISR lesions treated with PCB angioplasty from January 2014 to May
      2015 were retrospectively examined. Recurrent ISR was judged on 6-month follow-up
      angiography. Clinical, angiographic and procedural parameters were evaluated as
      possible predictors of recurrent ISR. Recurrent ISR occurred in 13.9% of lesions
      after PCB angioplasty. On multivariate analysis the following independent
      predictors of recurrent ISR were identified: (1) smaller acute gain after initial
      ballooning (OR, 3.06; 95% CI: 1.08-8.71; P=0.04); (2) geographic mismatch between
      PCB position and initial ballooning (OR, 5.59; 95% CI: 1.64-19.1; P=0.006); and
      (3) use of percutaneous transluminal coronary rotational atherectomy (PTCRA) at
      primary percutaneous coronary intervention (PCI; OR, 5.53; 95% CI: 1.89-16.2;
      P=0.002). CONCLUSIONS: Optimal expansion at initial ballooning before PCB
      angioplasty and careful positioning of PCB are important technical tips to
      prevent recurrent ISR after PCB angioplasty. Recurrent ISR occurred more
      frequently in severely calcified lesions that required PTCRA at primary PCI.

PMID- 28450677
TI  - Intra-arterial Contrasted Cone-beam Computed Tomography Assessment of Vessels
      Distal from Occluded Site in Acute Ischemic Stroke with Major Vessel Occlusion.
AB  - Characterization of vessels distal from occluded site is important when
      considering endovascular revascularization therapy (EVT) for acute ischemic
      stroke. The goal of this study was to assess the clinical value of intra-arterial
      contrasted high-resolution cone-beam computed tomography from the ascending aorta
      (Ao-CBCT) for visualization of the vessels distal from occluded site. Acute
      ischemic stroke patients with large vessel occlusion who were to undergo EVT were
      evaluated. In EVT, digital subtraction angiography (DSA) and Ao-CBCT were
      performed with local anesthesia. Ao-CBCT images were acquired in a 20-second
      rotational scan. Contrast medium was injected (1 mL/s for a total of 30 seconds
      using a 4-Fr catheter and an imaging delay of 10 seconds) from the ascending
      aorta. We assessed the image quality of Ao-CBCT and compared the visualization of
      the vessels distal from occluded site among magnetic resonance angiography (MRA),
      DSA and Ao-CBCT. We analyzed 14 patients (mean age, 66 years; three female
      patients). Stroke subtypes were cardiogenic (n = 6), atherothrombotic (n = 5) and
      others/unknown (n = 3). Occluded sites were middle cerebral artery (MCA) M1 (n =
      8), MCA M2 (n = 2), internal carotid artery (ICA) (n = 2), MCA M4 (n = 1) and
      basilar artery (BA) (n = 1). All obtained Ao-CBCT images successfully
      characterized the vessels distal from occluded site, and 11 images (79%) were
      excellent. In all cases, Ao-CBCT images could depict distal vessels with more
      detail when compared with MRA and DSA. Ao-CBCT is an efficient method to obtain
      detailed information regarding vessels distal from occluded site when compared
      with conventional examination methods.

PMID- 28450678
TI  - Association of High-Density Lipoprotein Subclasses with Carotid Intima-Media
      Thickness: Shimane CoHRE Study.
AB  - AIMS: Recent studies suggested that subclasses of high-density lipoprotein (HDL)
      may be a better biomarker to predict the risk of atherosclerotic disorders. We
      aimed to examine the association of HDL2- and HDL3-cholesterol (HDL2-C and HDL3
      C) with carotid intima-media thickness (IMT) using a new method to quantify the
      HDL-C subclasses. METHODS: Participants were 657 Japanese subjects (434 women)
      who received a health examination (mean age: 73 years). Serum samples were
      analyzed by the homogenous assay for HDL-C and HDL3-C. HDL2-C was calculated
      indirectly by subtracting HDL3-C from HDL-C. HDL3-C measured by this assay was
      well correlated with that measured by ultracentrifugation (r=0.898, p<0.001). The
      maximum IMT (max-IMT) and plaque score (PS) were evaluated by ultrasonography
      following the standard protocol. RESULTS: HDL3-C was associated with age both in
      men (r=-0.322, p<0.0001) and women (r=-0.315, p<0.0001). In a simple regression
      analysis, max-IMT showed an inverse association with HDL3-C, whereas no
      significant association was observed with HDL2-C. A multiple linear regression
      analysis indicated, however, that the association between HDL3-C and max-IMT was
      not significant in both aged and younger populations when age was included in the
      analysis. Further, not only HDL2-C but also HDL3-C was not a significant
      predictor of 'atherosclerotic arteries' defined as the max-IMT >=1.5 mm. Similar
      results were observed in the analysis on PS. CONCLUSIONS: Neither HDL3-C nor HDL2
      C was significantly associated with carotid atherosclerosis in the Japanese
      population in this study.

PMID- 28450679
TI  - The Combination Therapy of Fenofibrate and Ezetimibe Improved Lipid Profile and
      Vascular Function Compared with Statins in Patients with Type 2 Diabetes.
AB  - AIM: Elevated level of serum triglyceride (TG) is a characteristic of type 2
      diabetes. We evaluated the clinical significance of intervention for the serum TG
      levels in the fasting and postprandial states in patients with type 2 diabetes.
      METHODS: Fifty patients with type 2 diabetes, treated with statins, were selected
      and divided into two groups. One group was treated with a combination of
      fenofibrate and ezetimibe (F/E group) and the other group with statins (statin
      group) for 12 weeks. The lipoprotein profile of both groups was compared using
      high-performance liquid chromatography, and the vascular function was assessed
      using flow-mediated dilation (FMD) at the forearm. RESULTS: The levels of very
      low-density lipoprotein (VLDL) cholesterol, malondialdehyde low-density
      lipoprotein (MDA-LDL), total TG, chylomicron-TG, VLDL-TG, and HDL-TG decreased in
      the F/E group, whereas those of HDL cholesterol increased. Furthermore, the peak
      particle size of LDL increased, but that of HDL decreased in the F/E group. The
      combination treatment significantly improved the FMD. The change in the
      cholesterol level in a very small fraction of HDL was a significant independent
      predictor for determining the improvement of FMD (p<0.01). CONCLUSIONS: Compared
      with the treatment with statins, the treatment with the combination of
      fenofibrate and ezetimibe effectively controlled the LDL cholesterol and TG
      levels, increased the HDL cholesterol level, especially in its small fraction,
      and improved vascular function of patients with type 2 diabetes.

PMID- 28450680
TI  - Progression of Carotid Atherosclerosis in Two Japanese Populations with Different
      Lifestyles.
AB  - AIM: We have conducted medical surveys on two Japanese populations (Japanese
      Americans living in the US and native Japanese living in Japan) to investigate
      the impact of westernization of lifestyles on diseases in Japanese people. A 1998
      survey revealed that the progression of carotid intima-media wall thickness (IMT)
      was faster by approximately 20 years in Japanese Americans than in native
      Japanese. In this study, we compared the progression of atherosclerosis in native
      Japanese versus that in Japanese Americans using carotid IMT data from medical
      examinations conducted in the 2010s. METHODS: This study included 115 native
      Japanese living in Hiroshima who underwent a medical examination in 2014 and 112
      Japanese Americans living in Hawaii who underwent a medical examination in 2012,
      excluding those receiving medication for diabetes mellitus (DM) or dyslipidemia.
      Carotid IMT was compared between the two Japanese populations. RESULTS: Serum
      total and low-density lipoprotein cholesterol levels were significantly higher in
      native Japanese than in Japanese Americans. The median carotid IMT was
      significantly greater in Japanese Americans than in native Japanese [median (25th
      75th percentile): 1.27 (0.86-2.02) mm vs. 1.00 (0.80-1.30) mm, P =0.001].
      Regression curves showed that the age at which IMT exceeded 1.1 mm was estimated
      at >50 years in Japanese Americans and at approximately 60 years in native
      Japanese. CONCLUSIONS: According to surveys conducted in 2012 and 2014, carotid
      IMT was still greater in Japanese Americans than in native Japanese. However, a
      comparison with data from the 1998 survey showed that current native Japanese had
      higher serum lipid levels and more advanced atherosclerosis.

PMID- 28450681
TI  - HDL3 Cholesterol Levels in an Elderly Population.

PMID- 28450682
TI  - Clinical Serum Therapy: Benefits, Cautions, and Potential Applications.
AB  - Blood serum from immunized humans or animals (e.g., horses) contains relevant
      antibodies and has been used as serum therapy to treat many diseases or
      envenomation events. The effectiveness of blood serum was initially discovered in
      1890 when Kitasato and von Behring observed the effectiveness of this type of
      therapy against diphtheria and tetanus. Serum therapies played an important role
      in the advancement of modern medicine prior to the development of penicillin and
      steroids. At present, several types of serum therapy remain in clinical use.
      However, some physicians have a limited understanding of the nature and the
      benefits of serum therapy and the factors that require particular attention. In
      this review, we set out to clarify the benefits, cautions, and potential
      applications of serum therapy in the context of conditions such as gas gangrene,
      diphtheria, botulism, and tetanus and bites from three snake species (mamushi,
      habu, and yamakagashi) and the redback spider. It is hoped that this review will
      help clinicians to learn about clinical serum therapies and become familiar with
      their applications.

PMID- 28450683
TI  - Coil Intrabronchial Migration in an Arteriovenous Malformation Patient Treated 10
      Years Ago.
AB  - A 56-year-old male who had received transcatheter coil deposition 10 years ago
      for an arteriovenous malformation (AVM) was admitted to our hospital because of
      persistent hemosputum. Chest radiograph and bronchoscopy revealed straightened
      coil bundles in his air way. Recently, less invasive transcatheter intervention
      has been performed more frequently for treatment of AVM than surgical resection.
      In our case, however, chest radiography and bronchoscopy showed that the coils
      might migrate from the deposited site to the airway. Then, right lower lobectomy
      was undertaken. In AVM patient who received coil deposition, a long-term follow
      up is recommended, and surgical resection should be carried out if necessary.

PMID- 28450684
TI  - The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of
      144 cases.
AB  - Diagnostic delay of tumor induced osteomalacia (TIO) is common in clinic
      practice. To investigate the diagnostic condition of TIO in China and raise
      clinicians' awareness of TIO, we retrospectively analyzed clinical
      manifestations, biochemical features, and specially evaluated missed diagnoses
      and misdiagnoses among 144 TIO patients from Peking Union Medical College
      Hospital during December 1982 to December 2014. Clinical presentations of TIO
      mainly included bone pain, difficulty in walking, pathological fractures, muscle
      weakness, and height loss. TIO patients demonstrated hypophosphatemia (0.48+/
      0.13 mmol/L), elevated serum alkaline phosphatase (277.9+/-152.6 U/L), reduced
      tubular maximum for phosphorus/glomerular filtration rate (0.39+/-0.14) and
      markedly elevated serum fibroblast growth factor 23 (FGF23) (median level 302.9
      pg/mL). The average time from onset to a correct diagnosis was 2.9+/-2.3 years
      while the mean duration from onset to tumor resection was 5.4+/-4.2 years. The
      initial misdiagnosis rate was 95.1% (137/144) and 240 case-times of misdiagnoses
      occurred among the 144 cases. The most frequent misdiagnoses were intervertebral
      disc herniation, spondyloarthritis (including ankylosing spondylitis) and
      osteoporosis. A total of 43.1% (62/144) cases with hypophosphatemia presented on
      their laboratory sheets were neglected and missed diagnosed. Our study showed
      that TIO was frequently misdiagnosed and missed diagnosed due to its rarity,
      insidious onset, nonspecific clinical manifestations and clinicians' poor
      recognition. It is necessary to test serum phosphorus in patients with
      musculoskeletal symptoms and difficulty in walking. The measurement of serum
      FGF23 is rather valuable. Once hypophosphatemia is discovered, TIO should be
      suspected and it is highly recommended to search for tumors and perform curative
      surgery.

PMID- 28450685
TI  - Acyclovir resistant acute herpes simplex encephalitis associated with acute
      retinal necrosis: A case report and review of the literature.
AB  - A 55-year-old man was admitted to our hospital for investigation of high fever,
      decreased consciousness and bilateral visual impairment. His cerebrospinal fluid
      analysis revealed pleocytosis of mononuclear cells and an increased protein
      concentration. FLAIR images revealed multiple high-intensity lesions in the
      frontal lobe, part of which was enhanced with gadolinium. Despite initiating
      treatment with acyclovir and corticosteroids, his consciousness and visual acuity
      deteriorated. Immunopathological examination of brain biopsies showed numerous
      herpes simplex virus type 2-positive neurons and macrophages, leading to a
      diagnosis of herpes simplex encephalitis (HSE). Fundoscopic examination revealed
      multiple foci of retinitis with vasculopathies, and inflammation in the anterior
      chamber and vitreous, indicating acute retinal necrosis (ARN). Foscarnet
      treatment was initiated in place of acyclovir and his consciousness improved,
      with a slight improvement in visual acuity. ARN is typically caused by a herpes
      virus infection limited to the eyeball, and rarely in combination with HSE. In
      such cases, there is a latency of approximately 2-4 weeks between ARN and the
      onset of encephalitis. Our case is unique in that HSE and ARN developed
      simultaneously, and it highlights that there may not always be a latency between
      the onsets of the two disorders. Finally, foscarnet should be considered in cases
      of HSE and ARN with acyclovir resistance.

PMID- 28450686
TI  - Serial neurophysiological and neurophysiological examinations for delayed facial
      nerve palsy in a patient with Fisher syndrome.
AB  - The patient was a 47-year-old man who presented with diplopia and gait
      instability with a gradual onset over the course of three days. Neurological
      examinations showed ophthalmoplegia, diminished tendon reflexes, and truncal
      ataxia. Tests for anti-GQ1b antibodies and several other antibodies to
      ganglioside complex were positive. We made a diagnosis of Fisher syndrome. After
      administration of intravenous immunoglobulin, the patient's symptoms gradually
      improved. However, bilateral facial palsy appeared during the recovery phase.
      Brain MRI showed intensive contrast enhancement of bilateral facial nerves.
      During the onset phase of facial palsy, the amplitude of the compound muscle
      action potential (CMAP) in the facial nerves was preserved. During the peak
      phase, the facial CMAP amplitude was within the lower limit of normal values, or
      mildly decreased. During the recovery phase, the CMAP amplitude was normalized,
      and the R1 and R2 responses of the blink reflex were prolonged. The delayed
      facial nerve palsy improved spontaneously, and the enhancement on brain MRI
      disappeared. Serial neurophysiological and neuroradiological examinations
      suggested that the main lesions existed in the proximal part of the facial nerves
      and the mild lesions existed in the facial nerve terminals, probably due to
      reversible conduction failure.

PMID- 28450687
TI  - Thymoma with immunodeficiency/Good syndrome associated with myasthenia gravis.
AB  - Good syndrome is a rare condition in which thymoma is associated with
      hypogammaglobulinemia; it is characterized by repeated respiratory or systemic
      infections caused by bacteria, viruses, and fungi, as well as with various
      autoimmune disorders such as pure red cell aplasia. A 65-year-old woman was
      admitted to our hospital with ptosis and abdominal muscle weakness. Based on the
      presence of anti-acetylcholine receptor (Ach-R) antibodies, she was diagnosed
      with myasthenia gravis (MG). At that time, invasive thymoma of Masaoka stage IVa
      was also detected. Regression of thymoma and clinical remission of MG was
      achieved by chemotherapy followed by high-dose corticosteroid. However, several
      months later, the patient started developing repeated bacterial respiratory tract
      infections, cytomegalovirus infections, and esophageal and systemic candidiasis.
      Laboratory tests revealed a marked decrease of serum gamma-globulin levels (IgG
      586 mg/dl, IgA 32 mg/dl, IgM 29 mg/dl) and severe reduction in the B cells ratio,
      as well as a decrease in the CD4+CD25+T cell to CD4+CD25-T cell ratio indicative
      of deregulation of CD4+T cell activation. These results suggested that the
      patient impaired humoral and cell-mediated immune responses. We continued the
      treatment with antibiotics and regular immunoglobulin supplementation through
      intravenous injections. Although autoimmune disorders are often observed in Good
      syndrome, the association with MG is quite rare. The case report is followed by
      the review of literature.

PMID- 28450688
TI  - A case of 55-year-old man with first-ever generalized seizure diagnosed with
      Sturge-Weber syndrome type III by characteristic MRI findings.
AB  - A 55-year-old man with no mental retardation had presented a history of frequent
      transient clumsiness of his right upper and lower extremities for about 20 years.
      He was admitted to a general hospital with weakness of right side of the body,
      and first-ever generalized seizure attack occurred the next day. Brain CT showed
      calcification in the left cerebral cortices. So he was referred to our hospital.
      On neurological examination, he had mild clumsiness of his right upper limb and
      right pyramidal tract sign. He had neither facial port-wine stain nor glaucoma.
      The blood test and cerebrospinal fluid analysis were unremarkable.
      Electroencephalogram showed slowing and reduction of activity at the left frontal
      and parietal areas with no epileptic activities. Brain CT showed "tram-track
      calcification" and lobar atrophy in the left fronto-parietal cortices.
      Susceptibility weighted imaging (SWI) on MRI revealed enlarged transmedullary
      veins in the left periventricular white matter and low intensity lesions along
      the cortical gyri. Post gadolinium fluid-attenuated inversion recovery imaging
      (FLAIR-Gd) showed leptomeningeal enhancement in the left fronto-parietal lobes
      more extensively than those by post gadolinium T1-weighted image. Brain perfusion
      single photon emission computed tomography with a technetium-99m-ethyl cysteinate
      dimer (99mTc-ECD SPECT) revealed hypoperfusion in the fronto-parietal lobes.
      These clinical and neuroimaging findings were compatible with type III Sturge
      Weber syndrome (SWS). His condition was improved after treatment with oral
      levetiracetam (1,000 mg daily). Although adult-onset type III SWS is very rare,
      it is important to perform SWI and post-contrast FLAIR for assessing
      leptomeningeal angioma in patients with seizure with focal cortical calcification
      even if they have no facial nevus.

PMID- 28450689
TI  - The second paradigm shift occurred on acute stroke therapy.
AB  - Outcome of acute stroke patients with embolic large vessel occlusion can be
      improved dramatically, if the effective and rapid reperfusion of the occluded
      vessel achieved. Since 2015, when the evidence of acute endovascular therapy
      established its efficacy, such scenario became no longer uncommon. Along with
      introduction of direct oral anticoagulant (DOAC), many options of antithrombotic
      therapy for acute ischemic stroke also became available. This review summarize
      the recent advances on acute ischemic stroke therapy.

PMID- 28450690
TI  - A case of chronic sarcoid myopathy with Basedow's disease and Sjogren's syndrome:
      A case series of sarcoid myopathy.
AB  - We report a 62-year-old woman with a history of Basedow's disease and Sjogren's
      syndrome who presented with slowly progressive limb muscle weakness over the
      course of ten years. On physical examination, she had dry eye and mouth, but was
      otherwise normal. Neurological examination revealed symmetrical proximal dominant
      muscle weakness. Polymyositis was suspected at initial diagnosis due to her
      clinical course, physical examination, and autoimmune disease. However, the final
      diagnosis based on a muscle biopsy was the chronic myopathic type of sarcoid
      myopathy. Among 25 definite sarcoid myopathy cases in the National Center of
      Neurology and Psychiatry muscle repository from 2010 to 2015, 6/25 had autoimmune
      diseases. All 6 patients were female and had the chronic myopathic type of
      sarcoid myopathy. The number of patients with Sjogren's syndrome, thyroid
      disease, autoimmune hepatitis, and idiopathic thrombocytopenia were 4, 1, 1, and
      1, respectively. Only the present case had both thyroid disease and Sjogren's
      syndrome. In conclusion, the chronic myopathic type of sarcoid myopathy is one
      possibility to consider in patients who present with progressive myopathy
      together with autoimmune diseases.

PMID- 28450691
TI  - Acute encephalopathy due to angel's trumpet intoxication: A case report and
      literature review.
AB  - We report two cases (a married couple) of intoxication due to angel's trumpet
      ingestion. Case 1: A 71-year-old woman was found lying unconscious on the sofa at
      home and was brought to our hospital by ambulance. She showed mydriatic
      anisocoria, and an intracerebral lesion was suspected. However, the brain
      magnetic resonance imaging showed no abnormal lesion and acute encephalopathy of
      unknown cause was diagnosed. Case 2: A 68-year-old man (husband of the patient of
      Case 1) showed alteration of consciousness with agitation and was admitted to our
      hospital on the next day. He also had slight mydriasis. As his manifestations
      were similar to those of his wife, we studied their medical history again. We
      found that they mistook the roots of angel's trumpet for burdock and cooked and
      ate them. This intoxication causes characteristic encephalopathy with altered
      consciousness and mydriasis. In the case of anisocoria or mild mydriasis, the
      diagnosis is difficult sometimes. The intoxication occurred within a family; this
      was a clue to the correct diagnosis. Severe cases exhibit pyramidal signs and
      symptoms or convulsion, and deaths have been reported. Angel's trumpet
      intoxication is an important neurological emergency.

PMID- 28450692
TI  - The ethyl acetate fraction of a methanolic extract of unripe noni (Morinda
      citrifolia Linn.) fruit exhibits a biphasic effect on the dopaminergic system in
      mice.
AB  - In earlier ex vivo studies, we reported the biphasic effect of a methanolic
      extract of unripe Morinda citrifolia fruit (MMC) on dopamine-induced
      contractility in isolated rat vas deferens preparations. The present in vivo
      study was designed and undertaken to further explore our earlier ex vivo
      findings. This study examined the effect of the ethyl acetate fraction of a
      methanolic extract of unripe Morinda citrifolia Linn. fruit (EA-MMC; 5-100 mg/kg,
      p.o.) on the dopaminergic system using mouse models of apomorphine-induced
      climbing time and climbing behavior, methamphetamine-induced stereotypy
      (sniffing, biting, gnawing, and licking) and haloperidol-induced catalepsy using
      the bar test. Acute treatment with EA-MMC at a low dose (25 mg/kg, p.o.)
      significantly attenuated the apomorphine-induced climbing time and climbing
      behavior in mice. Similarly, EA-MMC (5 and 10 mg/kg, p.o.) significantly
      inhibited methamphetamine-induced stereotyped behavior in mice. These results
      demonstrated that the antidopaminergic effect of EA-MMC was observed at
      relatively lower doses (<25 mg/kg, p.o.). On the other hand, EA-MMC showed
      dopaminergic agonistic activity at a high dose (3,000 mg/kg, p.o.), which was
      evident from alleviation of haloperidol (a dopamine D2 blocker)-induced catalepsy
      in mice. Therefore, it is concluded that EA-MMC might possess a biphasic effect
      on the dopaminergic system, i.e., an antagonistic effect at lower doses (<25
      mg/kg, p.o.) and an agonistic effect at higher doses (>1,000 mg/kg, p.o.).
      However, further receptor-ligand binding assays are necessary to confirm the
      biphasic effects of M. citrifolia fruit on the dopaminergic system.

PMID- 28450693
TI  - Lycorine Induces Apoptosis of A549 Cells via AMPK-Mammalian Target of Rapamycin
      (mTOR)-S6K Signaling Pathway.
AB  - BACKGROUND This study was designed to investigate the effect of lycorine (LY) on
      the AMPK-mTOR-S6K signaling pathway and to clarify its role in autophagy and
      apoptosis. MATERIAL AND METHODS Various concentrations of LY were used to treat
      non-small cell lung carcinoma A549 cells. The MTT assay was used to measure cell
      viability and acridine orange staining was used to detect cell morphology
      changes. Western blot analysis was used to test the effect of LY on the
      expression levels of LC3, caspase 3, and other proteins involved in the AMPK-mTOR
      S6K signaling pathway. RESULTS The half maximal inhibitory concentration (IC50)
      of LY after 24-h treatment was 8.5 MUM, with stronger inhibitory effect of 24-h
      LY treatment over 12-h LY treatment. Morphological observation showed that lower
      doses (4 MUM and 8 MUM) of LY treatment induced A549 cell death mainly caused by
      autophagy, whereas the higher dose (16 MUM) of LY treatment induced A549 cell
      death, mainly caused by apoptosis. Furthermore, 8 MUM LY caused the highest
      conversion of LC3-II from LC3-I. All LY treatments activated caspase-3. LY
      treatment also promoted AMPK phosphorylation (Thr172) and inhibited the
      phosphorylation of mTOR and S6K. CONCLUSIONS LY induced apoptosis of A549 cells
      by regulating the AMPK-mTOR-S6K signaling pathway. Lower levels (4~8 MUM) of LY
      induced autophagy contributed to LY-induced apoptosis.

PMID- 28450694
TI  - Diagnostic Approach in Biliary Strictures After Pediatric Liver Transplantation.
AB  - BACKGROUND The diagnosis of post-liver transplant biliary strictures (BS)
      requires a high degree of clinical suspicion because of the diversity of symptoms
      and usually mild clinical presentation. If quickly treated, successful outcome is
      achieved most cases. The aim of our study was to analyze the value of diagnostic
      methods in BS after pediatric LTx. MATERIAL AND METHODS We retrospectively
      reviewed clinical data of children with BS after liver transplantation, with the
      main focus on diagnostic methods, including imaging studies and histology. All
      patients underwent endoscopic, transhepatic, or surgical treatment of the
      stricture. RESULTS Sixty-seven patients after LTx performed at the median age of
      9.1 years (0.4-18) developed BS, mostly within the first 12 months (40%).
      Laboratory findings at diagnosis were: bilirubin 4.65 (5.8+/-SD), GGTP 434
      (382.9+/-SD), and ALT 126.5 (116.8+/-SD); 16 patients presented with bilirubin
      level <1 mg% and 4 with GGTP below 100 IU. Ultrasound scan (USS) visualized
      dilatation of the bile ducts in 53 (79%) patients. Overall sensitivity of
      hepatobiliary scintigraphy (HBS) was 93%, with dilatation of bile ducts in 69%
      and impaired excretion in 68% of patients. MRCP showed 100% accuracy in detecting
      biliary dilatation and a stricture was visualized in 39%. Liver histology was
      consistent with biliary obstruction in 66%. Treatment of BS was successful in the
      majority of cases, with 89% graft survival. CONCLUSIONS Non-invasive
      investigations are highly sensitive in post-transplant BS and should play the key
      role in diagnostic algorithms.

PMID- 28450695
TI  - Hyperphosphatemia, a Cause of High Anion Gap Metabolic Acidosis: Report of a Case
      and Review of the Literature.
AB  - BACKGROUND Hyperphosphatemia is a common problem in patients with kidney failure.
      It is usually mild and rarely severe enough to cause metabolic acidosis on its
      own. Besides kidney failure, use of phosphate containing enemas, rhabdomyolysis,
      and tumor lysis syndrome are common causes of severe hyperphosphatemia. CASE
      REPORT A 74-year-old man with a history of diabetes mellitus type II, arterial
      hypertension, and end stage renal disease, who was on hemodialysis and who had
      undergone hemicolectomy for ischemic bowel disease, and had not eaten for several
      days, developed severe metabolic acidosis, with an anion gap (AG) of 31 meq/L, 
      uncorrected for serum albumin. At that time he had a high level of beta
      hydroxybutyrate and severe hyperphosphatemia (16.5 mg/dL). Metabolic acidosis and
      hyperphosphatemia were corrected with hemodialysis, confirming the role of
      hyperphosphatemia in the development of high AG metabolic acidosis. CONCLUSIONS
      Although our patient had many reasons to develop high AG metabolic acidosis,
      hyperphosphatemia played a significant role in his acidosis. Severe
      hyperphosphatemia is rarely mentioned as a cause of high AG acidosis. It should
      be added to the long list of causes of this metabolic disorder. Physiological
      basis of acid base changes are discussed.

PMID- 28450697
TI  - Eigenvector Centrality is a Metric of Elastomer Modulus, Heterogeneity, and
      Damage.
AB  - We present an application of eigenvector centrality to encode the connectivity of
      polymer networks resolved at the micro- and meso-scopic length scales. This
      method captures the relative importance of different nodes within the network
      structure and provides a route toward the development of a statistical mechanics
      model that correlates connectivity with mechanical response. This scheme may be
      informed by analytical and semi-analytical models for the network structure, or
      through direct experimental examination. It may be used to predict the reduction
      in mechanical performance for heterogeneous materials subjected to specific modes
      of damage. Here, we develop the method and demonstrate that it leads to the
      prediction of established trends in elastomers. We also apply the model to the
      case of a self-healing polymer network reported in the literature, extracting
      insight about the fraction of bonds broken and re-formed during strain and
      recovery.

PMID- 28450696
TI  - Alginate Particles with Ovalbumin (OVA) Peptide Can Serve as a Carrier and
      Adjuvant for Immune Therapy in B16-OVA Cancer Model.
AB  - BACKGROUND Alginate is a natural polysaccharide obtained from brown algae and has
      been shown to have numerous applications in biomedical science, such as wound
      healing, delivery of bioactive agents, and cell transplantation. Ovalbumin (OVA)
      peptide 323-339 has been reported to be involved in immune response.  MATERIAL
      AND METHODS This work investigated the use of alginate particles as a carrier and
      adjuvant for the immune therapy of cancer. Alginate particles loaded with OVA
      peptide were produced via emulsion. A tumor model was established in C57BL/6J
      mice via subcutaneous injection of 3*105 B16-OVA tumor cells. The effect of
      alginate/OVA peptide on cell viability was analyzed by use of the CCK-8 assay
      kit. Activation of macrophages was examined by checking cell surface makers CD40
      and CD86 by FACs. RESULTS Alginate/OVA peptide inhibited tumor progression more
      effectively than using the peptide alone. The viability and uptake study
      illustrated that this particle is safe and non-toxic. The activation study
      demonstrated that alginate particles can promote the activation of surface
      markers on macrophages. ELISA assay showed that the particles with peptide can
      promote the secretion of inflammatory and effector cytokines from macrophages. 
      CONCLUSIONS This study demonstrated that alginate has dual functions in immune
      therapy of cancer, serving both as a carrier and an adjuvant.

PMID- 28450698
TI  - Deficiency of CCN5/WISP-2-Driven Program in breast cancer Promotes Cancer
      Epithelial cells to mesenchymal stem cells and Breast Cancer growth.
AB  - Breast cancer progression and relapse is conceivably due to tumor initiating
      cells (TICs)/cancer stem cells. EMT (epithelial-mesenchymal-transition)-signaling
      regulates TICs' turnover. However, the mechanisms associated with this episode
      are unclear. We show that, in triple-negative-breast cancer (TNBC) cells enriched
      with TICs, CCN5 significantly blocks cellular growth via apoptosis, reversing EMT
      signaling and impairing mammosphere formation, thereby blocking the tumor-forming
      ability and invasive capacity of these cells. To corroborate these findings, we
      isolated tumor-initiating side populations (SP) and non-side population (NSP or
      main population) from MCF-7 cell line, and evaluated the impact of CCN5 on these
      subpopulations. CCN5 was overexpressed in the NSP but downregulated in the SP.
      Characteristically, NSP cells are ER-alpha positive and epithelial type with
      little tumorigenic potency, while SP cells are very similar to triple-negative
      ones that do not express ER-alpha- and Her-2 and are highly tumorigenic in
      xenograft models. The overexpression of CCN5 in SP results in EMT reversion, ER
      alpha upregulation and delays in tumor growth in xenograft models. We reasoned
      that CCN5 distinguishes SP and NSP and could reprogram SP to NSP transition,
      thereby delaying tumor growth in the xenograft model. Collectively, we reveal how
      CCN5-signaling underlies the driving force to prevent TNBC growth and
      progression.

PMID- 28450699
TI  - A predation cost to bold fish in the wild.
AB  - Studies of predator-mediated selection on behaviour are critical for our
      understanding of the evolution and maintenance of behavioural diversity in
      natural populations. Consistent individual differences in prey behaviour,
      especially in the propensity to take risks ("boldness"), are widespread in the
      animal kingdom. Theory predicts that individual behavioural types differ in a
      cost-benefit trade-off where bolder individuals benefit from greater access to
      resources while paying higher predation-risk costs. However, explicitly linking
      predation events to individual behaviour under natural conditions is challenging
      and there is currently little data from the wild. We assayed individual behaviour
      and electronically tagged hundreds of fish (roach, Rutilus rutilus) before
      releasing them into their lake of origin, thereby exposing them to predation risk
      from avian apex predators (cormorants, Phalacrocorax carbo). Scanning for
      regurgitated tags at the cormorant roosting site provided data on individual
      predation events. We found that fish with higher boldness have a greater
      susceptibility to cormorant predation compared to relatively shy, risk-averse
      individuals. Our findings hereby provide unique and direct evidence of
      behavioural type-dependent predation vulnerability in the wild, i.e. that there
      is a predation cost to boldness, which is critical for our understanding of the
      evolution and maintenance of behavioural diversity in natural populations.

PMID- 28450700
TI  - Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy
      by Galectin-1 intranasal knock-down strategy.
AB  - In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in
      the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to
      brain transport. Gal-1 is overexpressed in GBM and drives chemo- and
      immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA
      targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the
      TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME
      composition, with reduced myeloid suppressor cells and regulatory T cells, and
      increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages'
      polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during
      GBM progression. These changes are accompanied by normalization of the tumor
      vasculature and increased survival for tumor bearing mice. The combination of
      siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination
      and PD-1 blocking) displays synergistic effects, increasing the survival of tumor
      bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM
      patients by matching the Gal-1 expression and their T cell signatures. These
      findings indicate that intranasal siGal-1 nanoparticle delivery could be a
      valuable adjuvant treatment to increase the efficiency of immune-checkpoint
      blockade and chemotherapy.

PMID- 28450701
TI  - Distributed atomic quantum information processing via optical fibers.
AB  - The qudit system may offer great flexibilities for quantum information
      processing. We investigate the possibility of realizing elementary quantum gates
      between two high-dimensional atoms in distant cavities coupled by an optical
      fiber. We show that highly reliable special swap gate is achievable by different
      detuning. The numerical simulation shows that the proposed elementary gate is
      robust against the atomic spontaneous decay, photon leakage of cavities and
      optical fibers by choosing the experimental parameters appropriately.

PMID- 28450702
TI  - Complement factors C4 and C3 are down regulated in response to short term
      overfeeding in healthy young men.
AB  - Insulin resistance is associated with high circulating level of complement factor
      C3. Animal studies suggest that improper complement activation mediates high-fat
      diet-induced insulin resistance. Individuals born with low birth weight (LBW) are
      at increased risk of developing insulin resistance. We hypothesized that high-fat
      overfeeding (HFO) increase circulating C3 and induce complement activation in a
      birth weight differential manner. Twenty LBW and 26 normal birth weight (NBW)
      young men were studied using a randomised crossover design. Insulin resistance
      was measured after a control-diet and after 5-days HFO by a hyperinsulinemic
      euglycemic-clamp. Circulating C4, C3, ficolins, mannose-binding-lectin,
      complement activation products C3bc, terminal complement complex (TCC) and
      complement activation capacity were determined using turbidimetry and ELISA. HFO
      induced peripheral insulin resistance in LBW individuals only, while both groups
      had the same degree of hepatic insulin resistance after HFO. Viewing all
      individuals circulating levels of C4, C3, C3bc, TCC and complement activation
      capacity decreased paradoxically along the development of insulin resistance
      after HFO (P = 0.0015, P < 0.0001, P = 0.01, P < 0.0001, P = 0.0002, P < 0.0001,
      P = 0.0006). Birth weight did not influence these results. This might reflect a
      hitherto unrecognized down-regulatory mechanism of the complement system. More
      human studies are needed to understand the underlying physiology and the
      potential consequences of these findings.

PMID- 28450703
TI  - Changes in the Prevalence of HBsAg and HBeAg: a Study of 8696 Parturients in a
      Well Vaccinated Area.
AB  - To elucidate the impact of a hepatitis B (HB) vaccination program on the
      prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well
      as the success rate of HBeAg clearance among parturients, we collected data on
      parturients who gave birth between 2000 and 2010, and recorded the HB status
      postpartum of those with positive HBeAg before birth. A total of 8696 parturients
      were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The
      prevalence of HBsAg decreased over the study period, particularly in the
      vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign
      parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and
      those with a higher body mass index (>24 kg/m2) had earlier HBeAg clearance
      (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for
      HBeAg before birth became negative 5 years after delivery. In conclusion, the
      downward trend in HB infection with more significance among vaccinated
      parturients reflects effective prevention and the impact of universal HB
      immunization. Nonetheless, aggressive follow-up is necessary for parturients who
      are persistently positive for HBeAg postpartum, as well as developing different
      public health policies for foreign parturients from endemic areas.

PMID- 28450704
TI  - Melanoma: a global perspective.
AB  - Most of our current knowledge of melanoma is derived from the study of patients
      from populations of European descent, for whom public health, sun protection
      initiatives and screening measures have appreciably decreased disease mortality.
      Notably, some melanoma subtypes that most commonly develop in other populations
      are not associated with exposure to ultraviolet (UV) light, suggesting a
      different disease aetiology. Further study of these subtypes is necessary to
      understand their risk factors and genomic architecture, and to tailor therapies
      and public health campaigns to benefit patients of all ethnic groups.

PMID- 28450706
TI  - Intracellular symbiosis of algae with possible involvement of mitochondrial
      dynamics.
AB  - Algal endosymbiosis is widely present among eukaryotes including many protists
      and metazoans. However, the mechanisms involved in their interactions between
      host and symbiont remain unclear. Here, we used electron microscopy and three
      dimensional reconstruction analyses to examine the ultrastructural interactions
      between the symbiotic zoochlorella and the organelles in the host Paramecium
      bursaria, which is a model system of endosymbiosis. Although in chemically fixed
      samples the symbiotic algae show no direct structural interactions with the host
      organelles and the perialgal vacuole membrane (PVM), in cryofixed P. bursaria
      samples the intimate connections were identified between the host mitochondria
      and the symbiotic algae via the PVM. The PVM was closely apposed to the cell wall
      of the symbiotic algae and in some places it showed direct contacts to the host
      mitochondrial membrane and the cell wall of the symbiotic algae. Further, the PVM
      associated mitochondria formed a mitochondrial network and were also connected to
      host ER. Our observations propose a new endosymbiotic systems between the host
      eukaryotes and the symbionts where the benefiting symbiosis is performed through
      intimate interactions and an active structural modification in the host
      organelles.

PMID- 28450707
TI  - Post-Surgery Glioma Growth Modeling from Magnetic Resonance Images for Patients
      with Treatment.
AB  - Reaction diffusion is the most common growth modelling methodology due to its
      simplicity and consistency with the biological tumor growth process. However,
      current extensions of the reaction diffusion model lack one or more of the
      following: efficient inclusion of treatments' effects, taking into account the
      viscoelasticity of brain tissues, and guaranteed stability of the numerical
      solution. We propose a new model to overcome the aforementioned drawbacks. Guided
      by directional information derived from diffusion tensor imaging, our model
      relates tissue heterogeneity with the absorption of the chemotherapy, adopts the
      linear-quadratic term to simulate the radiotherapy effect, employs Maxwell
      Weichert model to incorporate brain viscoelasticity, and ensures the stability of
      the numerical solution. The performance is verified through experiments on
      synthetic and real MR images. Experiments on 9 MR datasets of patients with low
      grade gliomas undergoing surgery with different treatment regimens are carried
      out and validated using Jaccard score and Dice coefficient. The growth simulation
      accuracies of the proposed model are in ranges of [0.673 0.822] and [0.805 0.902]
      for Jaccard scores and Dice coefficients, respectively. The accuracies decrease
      up to 4% and 2.4% when ignoring treatment effects and the tensor information,
      while brain viscoelasticity has no significant impact on the accuracies.

PMID- 28450708
TI  - Elevated free triiodothyronine may lead to female sexual dysfunction in Chinese
      urban women: A hospital-based survey.
AB  - Research on female sexual dysfunction (FSD) is limited, especially in China, due
      to conservative culture and beliefs. There has been a dearth of FSD screening
      research in China since the optimal cutoff value of the Chinese version of the
      Female Sexual Function Index (CVFSFI) was determined in 2014. At the same time,
      the relationship between thyroid hormones and FSD has seldom been explored in
      Chinese women. Therefore, hospital-based research was conducted to elucidate FSD
      frequency and risk factors. Women who underwent a check-up at the Health
      Promotion Center were approached to participate and, if consented, were enrolled
      in the study. Demographic and socioeconomic data was extracted. All participants
      completed the CVFSFI and Beck Depression Inventory (BDI) self-report
      questionnaires and underwent thyroid hormone tests. A total of 1119 participants
      were included in the final analysis, with a mean age of 38.6 +/- 7.6 years and
      average CVFSFI score of 25.7 +/- 3.9. The frequency of FSD among the participants
      in this hospital-based cross-sectional study was 26.5%. In addition to age,
      menopause, parity and depression status as risk factor, and annual income (40,000
      100,000 RMB/year) and educational background (>=university) as protective factor,
      elevated free triiodothyronine (fT3) was identified as an independent risk factor
      of FSD.

PMID- 28450705
TI  - The ETS family of oncogenic transcription factors in solid tumours.
AB  - Findings over the past decade have identified aberrant activation of the ETS
      transcription factor family throughout all stages of tumorigenesis. Specifically
      in solid tumours, gene rearrangement and amplification, feed-forward growth
      factor signalling loops, formation of gain-of-function co-regulatory complexes
      and novel cis-acting mutations in ETS target gene promoters can result in
      increased ETS activity. In turn, pro-oncogenic ETS signalling enhances
      tumorigenesis through a broad mechanistic toolbox that includes lineage
      specification and self-renewal, DNA damage and genome instability, epigenetics
      and metabolism. This Review discusses these different mechanisms of ETS
      activation and subsequent oncogenic implications, as well as the clinical utility
      of ETS factors.

PMID- 28450709
TI  - Multi-functional Ultrasonic Micro-elastography Imaging System.
AB  - In clinical decision making, in addition to anatomical information, biomechanical
      properties of soft tissues may provide additional clues for disease diagnosis.
      Given the fact that most of diseases are originated from micron sized structures,
      an elastography imaging system of fine resolution (~100 um) and deep penetration
      depth capable of providing both qualitative and quantitative measurements of
      biomechanical properties is desired. Here, we report a newly developed multi
      functional ultrasonic micro-elastography imaging system in which acoustic
      radiation force impulse imaging (ARFI) and shear wave elasticity imaging (SWEI)
      are implemented. To accomplish this, the 4.5 MHz/40 MHz transducer were used as
      the excitation/detection source, respectively. The imaging system was tested with
      tissue-mimicking phantoms and an ex vivo chicken liver through 2D/3D imaging. The
      measured lateral/axial elastography resolution and field of view are 223.7 +/-
      20.1/109.8 +/- 6.9 um and 1.5 mm for ARFI, 543.6 +/- 39.3/117.6 +/- 8.7 um and 2
      mm for SWEI, respectively. These results demonstrate that the promising
      capability of this high resolution elastography imaging system for characterizing
      tissue biomechanical properties at microscale level and its translational
      potential into clinical practice.

PMID- 28450711
TI  - Pronounced Plasticity Caused by Phase Separation and beta-relaxation
      Synergistically in Zr-Cu-Al-Mo Bulk Metallic Glasses.
AB  - Bulk metallic glasses (BMGs) are known to have extraordinary merits such as
      ultrahigh strength and dynamic toughness etc. but tied to the detrimental
      brittleness, which has become a critical issue to the engineering application and
      understanding the glass nature. In this article, we report a new class of Zr-Cu
      Al-Mo BMGs with extraordinary plastic strain above 20%. "Work-hardening" effect
      after yielding in a wide range of plastic deformation process has been detected
      for this kind of BMGs. Compositional heterogeneity, which can be classified into
      ZrMo- and Cu-rich zones, was differentiated in this kind of BMG. Pronounced humps
      have been observed on the high frequency kinetic spectrum in Mo containing BMGs,
      which is the indicator of beta-relaxation transition. The underlying mechanism
      for the excellent plastic deforming ability of this class of BMGs is ascribed to
      the synergistic effects of soft ZrMo-rich glass formed through phase separation
      and abundant flow units which related to beta-relaxation.

PMID- 28450710
TI  - Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the
      Mutation Spectrum and Genotype-Phenotype Correlations in 27 Chinese Han Families.
AB  - Congenital cataract is the most frequent inherited ocular disorder and the most
      leading cause of lifelong visual loss. The screening of pathogenic mutations can
      be very challenging in some cases, for congenital cataracts are clinically and
      genetically heterogeneous diseases. The aim of this study is to investigate the
      mutation spectrum and frequency of 54 cartaract-associated genes in 27 Chinese
      families with congenital cataracts. Variants in 54 cataract-associated genes were
      screened by targeted next-generation sequencing (NGS) and then validated by
      Sanger sequencing. We identified pathogenic variants in 62.96% (17/27) of
      families, and over 52.94% (9/17) of these variants were novel. Among them, three
      are splicing site mutations, four are nonsense mutations, seven are missense
      mutations, two are frame shift mutations and one is intronic mutation. This
      included identification of: complex ocular phenotypes due to two novel PAX6
      mutations; progressive cortical cataract and lamellar cataract with lens
      subluxation due to two novel CRYGS mutations. Mutations were also found in rarely
      reported genes including CRYBA4, CRYBA2, BFSP1, VIM, HSF4, and EZR. Our study
      expands the mutation spectrum and frequency of genes responsible for congenital
      cataracts. Targeted next-generation sequencing in inherited congenital cataract
      patients provided significant diagnostic information.

PMID- 28450712
TI  - Monitoring Chemical Changes on the Surface of Kenaf Fiber during Degumming
      Process Using Infrared Microspectroscopy.
AB  - Degumming is the dominant method to obtain lignocellulosic fibers in the textile
      industry. Traditionally, wet chemistry methods are used to monitor the evolution
      of major chemical components during the degumming process. However, these methods
      lack the ability to provide spatial information for these heterogeneous
      materials. In this study, besides wet chemistry and scanning electron microscopy
      (SEM) analysis, a Fourier-transform infrared microspectroscopy (FTIRM) method was
      employed to monitor the changes in spatial distribution of the main chemical
      components on the kenaf surface during a steam explosion followed by chemical
      degum process. The results showed that hemicellulose and lignin were degummed at
      different rates, and the mechanisms of their degumming are different. The
      infrared microspectral images revealed the distribution changes of chemical
      components on the fiber bundle surface during the process, indicating that FTIRM
      is an effective tool to analyze the degumming process and improve degumming
      methods.

PMID- 28450715
TI  - Thomas Lynch.

PMID- 28450713
TI  - Decreased body mass index in the preclinical stage of autosomal dominant
      Alzheimer's disease.
AB  - The relationship between body-mass index (BMI) and Alzheimer's disease (AD) has
      been extensively investigated. However, BMI alterations in preclinical
      individuals with autosomal dominant AD (ADAD) have not yet been investigated. We
      analyzed cross-sectional data from 230 asymptomatic members of families with ADAD
      participating in the Dominantly Inherited Alzheimer Network (DIAN) study
      including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non
      carriers (NCs). Differences in BMI and their relation with cerebral amyloid load
      and episodic memory as a function of estimated years to symptom onset (EYO) were
      analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs,
      starting 11.2 years before expected symptom onset. However, the BMI curves begun
      to diverge already at 17.8 years before expected symptom onset. Lower BMI in
      preclinical MCs was significantly associated with less years before estimated
      symptom onset, higher global Abeta brain burden, and with lower delayed total
      recall scores in the logical memory test. The study provides cross-sectional
      evidence that weight loss starts one to two decades before expected symptom onset
      of ADAD. Our findings point toward a link between the pathophysiology of ADAD and
      disturbance of weight control mechanisms. Longitudinal follow-up studies are
      warranted to investigate BMI changes over time.

PMID- 28450714
TI  - A Zika virus from America is more efficiently transmitted than an Asian virus by
      Aedes aegypti mosquitoes from Asia.
AB  - Zika is a mosquito-borne disease associated with neurological disorders that
      causes an on-going pandemic. The first outbreak was recorded in Micronesia in
      2007, then in French Polynesia in 2014 from which it spread to South America in
      2015 and ignited a widespread epidemic. Interestingly, Zika outbreaks in Asia
      remained of moderate intensity although the virus is circulating. To understand
      these epidemiological variations, we investigated the entomological determinants
      of ZIKV transmission in Asia. We used oral infection of mosquitoes collected in
      Singapore to identify the vector species, to quantify the blood infection
      threshold and to compare transmissibility between an Asian ZIKV strain (H/PF13)
      and an American strain collected in Brazil (BE H 815744). We have confirmed the
      vector status of Aedes aegypti and determined that 103 pfu/ml of blood is
      sufficient to infect mosquitoes. We showed that only the American strain was
      present in the saliva 3 days post-infection, and that this strain had a 30-40%
      higher rate of saliva infection in Ae. aegypti from 3 to 14 days post-infection
      than the Asian strain. Our data suggests that American strains are more
      efficiently transmitted than Asian strains, which raises concerns about the
      introduction of American strains in Asia.

PMID- 28450717
TI  - FDA approves first deuterated drug.

PMID- 28450716
TI  - FDA approves dupilumab for severe eczema.

PMID- 28450718
TI  - Anticancer therapy: Re-educating macrophages.

PMID- 28450720
TI  - FDA approves first drug for primary progressive multiple sclerosis.

PMID- 28450719
TI  - Advances in islet encapsulation technologies.

PMID- 28450721
TI  - CAR T therapies drive into new terrain.

PMID- 28450722
TI  - Nine paths to PCSK9 inhibition.

PMID- 28450723
TI  - Direct Formation of Structural Components Using a Martian Soil Simulant.
AB  - Martian habitats are ideally constructed using only locally available soils;
      extant attempts to process structural materials on Mars, however, generally
      require additives or calcination. In this work we demonstrate that Martian soil
      simulant Mars-1a can be directly compressed at ambient into a strong solid
      without additives, highlighting a possible aspect of complete Martian in-situ
      resource utilization. Flexural strength of the compact is not only determined by
      the compaction pressure but also significantly influenced by the lateral boundary
      condition of processing loading. The compression loading can be applied either
      quasi-statically or through impact. Nanoparticulate iron oxide (npOx), commonly
      detected in Martian regolith, is identified as the bonding agent. Gas
      permeability of compacted samples was measured to be on the order of 10-16 m2,
      close to that of solid rocks. The compaction procedure is adaptive to additive
      manufacturing.

PMID- 28450724
TI  - Effect of Unsaturated Sn Atoms on Gas-Sensing Property in Hydrogenated SnO2
      Nanocrystals and Sensing Mechanism.
AB  - Sensing reaction mechanism is crucial for enhancing the sensing performance of
      semiconductor-based sensing materials. Here we show a new strategy to enhancing
      sensing performance of SnO2 nanocrystals by increasing the density of unsaturated
      Sn atoms with dangling bonds at the SnO2 surface through hydrogenation. A concept
      of the surface unsaturated Sn atoms serving as active sites for the sensing
      reaction is proposed, and the sensing mechanism is described in detail at atomic
      and molecule level for the first time. Sensing properties of other metal oxide
      sensors and catalytic activity of other catalysts may be improved by using the
      hydrogenation strategy. The concept of the surface unsaturated metal atoms
      serving as active sites may be very useful for understanding the sensing and
      catalytic reaction mechanisms and designing advanced sensing sensors, catalysts
      and photoelectronic devices.

PMID- 28450725
TI  - Heat shock protein70 is implicated in modulating NF-kappaB activation in alveolar
      macrophages of patients with active pulmonary tuberculosis.
AB  - Heat shock proteins (HSPs) have been shown to modulate NF-kappaB activation. It
      is unknown whether HSP70 plays a role in modulating NF-kappaB-mediated pro
      inflammatory cytokines released from alveolar macrophage (AM) of patients with
      active pulmonary tuberculosis (TB). Peripheral blood monocytes (PBMs) and AM were
      sampled from nineteen active TB patients and 14 healthy individuals. HSP70
      expression was 3-fold higher in AMs of active TB patients than normal subjects,
      and declined after receiving 3-month anti-TB treatment. Overexpression of HSP70
      by transfection with HSP70 plasmid decreased p-IkappaBalpha and p65 NF-kappaB
      activities. Inhibition of NF-kappaB activation using NF-kappaB or MAPK inhibitors
      increased HSP70 expression in AM of TB patients. Blocking p38- or ERK-MAPK
      decreased NF-kappaB and IkappaB activities, leading to up-regulated HSP70
      expression. Overexpression of HSP70 alone or with p38 or ERK inhibitors decreased
      TNF-alpha (57%, 83% and 74%, respectively) and IL-6 (53%, 70%, and 67%,
      respectively) release from macrophages of TB patients. In conclusion, HSP70
      modulates NF-kappaB activation in AM of TB patients, through inhibiting IkappaB
      alpha phosphorylation or acting as a chaperon molecule to prevent NF-kappaB
      binding to the target genes by facilitating degradation. The upregulated HSP70
      may suppress the release of pro-inflammatory cytokines during active PTB
      infection, and prevent overwhelming tissue damage.

PMID- 28450726
TI  - Effect of DRD4 receptor -616 C/G polymorphism on brain structure and functional
      connectivity density in pediatric primary nocturnal enuresis patients.
AB  - The dopamine D4 receptor (DRD4) promoter (-616; rs747302) has been associated
      with primary nocturnal enuresis (PNE); however, its relationship with
      neuroimaging has not been investigated. Therefore, we assessed the effects of the
      DRD4 -616 C/G single nucleotide polymorphism on the gray matter volume (GMV) and
      functional connectivity density (FCD) during resting-state functional magnetic
      resonance imaging in children with PNE using voxel-based morphometry and FCD
      methods. Genomic and imaging data were obtained from 97 children with PNE and 105
      healthy controls. DRD4 -616 C/G was genotyped. Arousal from sleep (AS) was
      assessed on a scale of 1-8. Both the main effect of genotype and the group
      (PNE/control)-by-genotype interaction on GMV and FCD were calculated. Our results
      showed that C-allele carriers were associated with a higher AS, decreased GMV and
      FCD in the pregenual anterior cingulate cortex; children with PNE carrying the C
      allele exhibit decreased GMV and FCD in the thalamus; however, controls carrying
      the C allele exhibit increased FCD in the posterior cingulate cortex. These
      effects of genetic variation of the DRD4 locus may help us understand the genetic
      susceptibility of the DRD4 -616 C allele to PNE.

PMID- 28450727
TI  - The CsHSP17.2 molecular chaperone is essential for thermotolerance in Camellia
      sinensis.
AB  - Small heat shock proteins (sHSPs) play important roles in responses to heat
      stress. However, the functions of sHSPs in tea plants (Camellia sinensis) remain
      uncharacterized. A novel sHSP gene, designated CsHSP17.2, was isolated from tea
      plants. Subcellular localization analyses indicated that the CsHSP17.2 protein
      was present in the cytosol and the nucleus. CsHSP17.2 expression was
      significantly up-regulated by heat stress but was unaffected by low temperature.
      The CsHSP17.2 transcript levels increased following salt and polyethylene glycol
      6000 treatments but decreased in the presence of abscisic acid. The molecular
      chaperone activity of CsHSP17.2 was demonstrated in vitro. Transgenic Escherichia
      coli and Pichia pastoris expressing CsHSP17.2 exhibited enhanced thermotolerance.
      The transgenic Arabidopsis thaliana exhibited higher maximum photochemical
      efficiencies, greater soluble protein proline contents, higher germination rates
      and higher hypocotyl elongation length than the wild-type controls. The
      expression levels of several HS-responsive genes increased in transgenic A.
      thaliana plants. Additionally, the CsHSP17.2 promoter is highly responsive to
      high-temperature stress in A. thaliana. Our results suggest that CsHSP17.2 may
      act as a molecular chaperone to mediate heat tolerance by maintaining maximum
      photochemical efficiency and protein synthesis, enhancing the scavenging of
      reactive oxygen species and inducing the expression of HS-responsive genes.

PMID- 28450728
TI  - Continuous Isotropic-Nematic Transition in Amyloid Fibril Suspensions Driven by
      Thermophoresis.
AB  - The isotropic and nematic (I + N) coexistence for rod-like colloids is a
      signature of the first-order thermodynamics nature of this phase transition.
      However, in the case of amyloid fibrils, the biphasic region is too small to be
      experimentally detected, due to their extremely high aspect ratio. Herein, we
      study the thermophoretic behaviour of fluorescently labelled beta-lactoglobulin
      amyloid fibrils by inducing a temperature gradient across a microfluidic channel.
      We discover that fibrils accumulate towards the hot side of the channel at the
      temperature range studied, thus presenting a negative Soret coefficient. By
      exploiting this thermophoretic behaviour, we show that it becomes possible to
      induce a continuous I-N transition with the I and N phases at the extremities of
      the channel, starting from an initially single N phase, by generating an
      appropriate concentration gradient along the width of the microchannel.
      Accordingly, we introduce a new methodology to control liquid crystal phase
      transitions in anisotropic colloidal suspensions. Because the induced order-order
      transitions are achieved under stationary conditions, this may have important
      implications in both applied colloidal science, such as in separation and
      fractionation of colloids, as well as in fundamental soft condensed matter, by
      widening the accessibility of target regions in the phase diagrams.

PMID- 28450729
TI  - Collateral sensitivity networks reveal evolutionary instability and novel
      treatment strategies in ALK mutated non-small cell lung cancer.
AB  - Drug resistance remains an elusive problem in cancer therapy, particularly for
      novel targeted therapies. Much work is focused upon the development of an arsenal
      of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to
      overcome the inevitable resistance that develops over time. Currently, after
      failure of first line ALK TKI therapy, another ALK TKI is administered, though
      collateral sensitivity is not considered. To address this, we evolved resistance
      in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK
      TKIs, and performed a collateral sensitivity analysis. All ALK inhibitor
      resistant cell lines displayed significant cross-resistance to all other ALK
      inhibitors. We then evaluated ALK-inhibitor sensitivities after drug holidays of
      varying length (1-21 days), and observed dynamic patterns of resistance. This
      unpredictability led us to an expanded search for treatment options, where we
      tested 6 further anti-cancer agents for collateral sensitivity among resistant
      cells, uncovering possibilities for further treatment, including cross
      sensitivity to standard cytotoxic therapies, as well as Hsp90 inhibitors. Taken
      together, these results imply that resistance to targeted therapy in non-small
      cell lung cancer is highly dynamic, and also one where there are many
      opportunities to re-establish sensitivities where there was once resistance. Drug
      resistance in cancer inevitably emerges during treatment; particularly with novel
      targeted therapies, designed to inhibit specific molecules. A clinically-relevant
      example of this phenomenon occurs in ALK-positive non-small cell lung cancer,
      where targeted therapies are used to inhibit the ALK-EML4 fusion protein. A
      potential solution to this may lie in finding drug sensitivities in the resistant
      population, termed collateral sensitivities, and then using these as second-line
      agents. This study shows how the evolution of resistance in ALK-positive lung
      cancer is a dynamic process through time, one in which patterns of drug
      resistance and collateral sensitivity change substantially, and therefore one
      where temporal regimens, such as drug cycling and drug holidays may have great
      benefit.

PMID- 28450730
TI  - Effectiveness of Immersive Videos in Inducing Awe: An Experimental Study.
AB  - Awe, a complex emotion composed by the appraisal components of vastness and need
      for accommodation, is a profound and often meaningful experience. Despite its
      importance, psychologists have only recently begun empirical study of awe. At the
      experimental level, a main issue concerns how to elicit high intensity awe
      experiences in the lab. To address this issue, Virtual Reality (VR) has been
      proposed as a potential solution. Here, we considered the highest realistic form
      of VR: immersive videos. 42 participants watched at immersive and normal 2D
      videos displaying an awe or a neutral content. After the experience, they rated
      their level of awe and sense of presence. Participants' psychophysiological
      responses (BVP, SC, sEMG) were recorded during the whole video exposure. We
      hypothesized that the immersive video condition would increase the intensity of
      awe experienced compared to 2D screen videos. Results indicated that immersive
      videos significantly enhanced the self-reported intensity of awe as well as the
      sense of presence. Immersive videos displaying an awe content also led to higher
      parasympathetic activation. These findings indicate the advantages of using VR in
      the experimental study of awe, with methodological implications for the study of
      other emotions.

PMID- 28450731
TI  - Improved survival in primary central nervous system lymphoma up to age 70 only: a
      population-based study on incidence, primary treatment and survival in the
      Netherlands, 1989-2015.

PMID- 28450732
TI  - Ultra-weak photon emission as a dynamic tool for monitoring oxidative stress
      metabolism.
AB  - In recent years, excessive oxidative metabolism has been reported as a critical
      determinant of pathogenicity in many diseases. The advent of a simple tool that
      can provide a physiological readout of oxidative stress would be a major step
      towards monitoring this dynamic process in biological systems, while also
      improving our understanding of this process. Ultra-weak photon emission (UPE) has
      been proposed as a potential tool for measuring oxidative processes due to the
      association between UPE and reactive oxygen species. Here, we used HL-60 cells as
      an in vitro model to test the potential of using UPE as readout for dynamically
      monitoring oxidative stress after inducing respiratory burst. In addition, to
      probe for possible changes in oxidative metabolism, we performed targeted
      metabolomics on cell extracts and culture medium. Lastly, we tested the effects
      of treating cells with the NADPH oxidase inhibitor diphenyleneiodonium chloride
      (DPI). Our results show that UPE can be used as readout for measuring oxidative
      stress metabolism and related processes.

PMID- 28450733
TI  - TET family dioxygenases and DNA demethylation in stem cells and cancers.
AB  - The methylation of cytosine and subsequent oxidation constitutes a fundamental
      epigenetic modification in mammalian genomes, and its abnormalities are
      intimately coupled to various pathogenic processes including cancer development.
      Enzymes of the Ten-eleven translocation (TET) family catalyze the stepwise
      oxidation of 5-methylcytosine in DNA to 5-hydroxymethylcytosine and further
      oxidation products. These oxidized 5-methylcytosine derivatives represent
      intermediates in the reversal of cytosine methylation, and also serve as stable
      epigenetic modifications that exert distinctive regulatory roles. It is becoming
      increasingly obvious that TET proteins and their catalytic products are key
      regulators of embryonic development, stem cell functions and lineage
      specification. Over the past several years, the function of TET proteins as a
      barrier between normal and malignant states has been extensively investigated.
      Dysregulation of TET protein expression or function is commonly observed in a
      wide range of cancers. Notably, TET loss-of-function is causally related to the
      onset and progression of hematologic malignancy in vivo. In this review, we focus
      on recent advances in the mechanistic understanding of DNA methylation
      demethylation dynamics, and their potential regulatory functions in cellular
      differentiation and oncogenic transformation.

PMID- 28450735
TI  - Methylation and demethylation of DNA and histones in chromatin: the most
      complicated epigenetic marker.

PMID- 28450734
TI  - Modulation of gene expression dynamics by co-transcriptional histone
      methylations.
AB  - Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly
      conserved methyl marks from yeast to humans, have profound roles in regulation of
      histone acetylation. These modifications function to recruit and/or activate
      distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs).
      Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2
      targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3'
      regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows
      elongation. Despite their important functions in deacetylation, no strong effects
      on global gene expression have been seen under optimized or laboratory growth
      conditions. Instead, H3K4me2-Set3 HDAC and Set2-Rpd3S pathways primarily delay
      the kinetics of messenger RNA (mRNA) and long noncoding RNA (lncRNA) induction
      upon environmental changes. A majority of mRNA genes regulated by these pathways
      have an overlapping lncRNA transcription either from an upstream or an antisense
      promoter. Surprisingly, the distance between mRNA and lncRNA promoters seems to
      specify the repressive effects of the two pathways. Given that co-transcriptional
      methylations and acetylation have been linked to many cancers, studying their
      functions in a dynamic condition or during cancer progression will be much more
      important and help identify novel genes associated with cancers.

PMID- 28450736
TI  - Histone lysine demethylases in mammalian embryonic development.
AB  - Post-translational modifications, such as methylation, acetylation and
      phosphorylation, of histone proteins play important roles in regulating dynamic
      chromatin structure. Histone demethylation has become one of the most active
      research areas of epigenetics in the past decade. To date, with the exception of
      histone H3 lysine 79 methylation, the demethylases for all major lysine
      methylation sites have been discovered. These enzymes have been shown to be
      involved in various biological processes, with embryonic development being an
      exciting emerging area. This review will primarily discuss the involvement of
      these demethylases in the regulation of mammalian embryonic development,
      including their roles in embryonic stem cell pluripotency, primordial germ cell
      (PGC) formation and maternal-to-zygotic transition.

PMID- 28450739
TI  - Comparing mortality risk of patients with acute hip fractures admitted to a major
      trauma centre on a weekday or weekend.
AB  - Proximal femoral fractures are a major public health concern with estimated
      annual direct and social costs amounting to L2 billion and average 30-day
      mortality risk of 7.5%. In response to the recent debate over out-of-hours
      hospital provision we investigated the 'weekend effect' at a major trauma centre,
      caring for acute injuries. A single centre, multi-surgeon review of 2060 patients
      performed. The distribution of patient and treatment variables compared in
      patients admitted on a weekday or the weekend. Fewer patients met performance
      indicators during weekend admission, time to surgery (63 vs. 71%) and time to
      geriatric review (86 vs. 91%). Weekend admission 30-day mortality was marginally
      lower than weekday (9.7% vs. 10.2%, OR 0.94, 95% CI 0.67 to 1.32, p = 0.7383).
      Increasing age, female gender, co-morbidities and confusion increased mortality
      risk. Binary regression analysis including these variables found no significant
      'weekend effect'. Despite the unit observing an increasing workload in the last
      five years, with meticulous workforce planning, senior doctor provisions and
      careful use of resources, it is possible to provide a seven-day fracture neck of
      femur service with no variation in thirty-day mortality by the day of admission.

PMID- 28450738
TI  - DNA methylation: an epigenetic mark of cellular memory.
AB  - DNA methylation is a stable epigenetic mark that can be inherited through
      multiple cell divisions. During development and cell differentiation, DNA
      methylation is dynamic, but some DNA methylation patterns may be retained as a
      form of epigenetic memory. DNA methylation profiles can be useful for the lineage
      classification and quality control of stem cells such as embryonic stem cells,
      induced pluripotent cells and mesenchymal stem cells. During cancer initiation
      and progression, genome-wide and gene-specific DNA methylation changes occur as a
      consequence of mutated or deregulated chromatin regulators. Early aberrant DNA
      methylation states occurring during transformation appear to be retained during
      tumor evolution. Similarly, DNA methylation differences among different regions
      of a tumor reflect the history of cancer cells and their response to the tumor
      microenvironment. Therefore, DNA methylation can be a useful molecular marker for
      cancer diagnosis and drug treatment.

PMID- 28450742
TI  - Aptamers as targeted therapeutics: current potential and challenges.

PMID- 28450741
TI  - Hospital readmissions for COPD: a retrospective longitudinal study.
AB  - : Prevention of chronic obstructive pulmonary disease hospital readmissions is an
      international priority aimed to slow disease progression and limit costs.
      Evidence of the risk of readmission and of interventions that might prevent it is
      lacking. We aimed to determine readmission risk for chronic obstructive pulmonary
      disease, factors influencing that risk, and variation in readmission risk between
      hospitals across 7.5 million people in London. This retrospective longitudinal
      observational study included all chronic obstructive pulmonary disease admissions
      to any hospital in the United Kingdom among patients registered at London general
      practices who had emergency National Health Service chronic obstructive pulmonary
      disease hospital admissions between April 2006 and March 2010. Influence of
      patient characteristics, geographical deprivation score, length of stay, day of
      week of admission or of discharge, and admitting hospital, were assessed using
      multiple logistic regression. 38,894 chronic obstructive pulmonary disease
      admissions of 20,932 patients aged >= 45 years registered with London general
      practices were recorded. 6295 patients (32.2%) had at least one chronic
      obstructive pulmonary disease readmission within 1 year. 1993 patients (10.2%)
      were readmitted within 30 days and 3471 patients (17.8%) were readmitted within
      90 days. Age and patient geographical deprivation score were very weak predictors
      of readmission. Rates of chronic obstructive pulmonary disease readmissions
      within 30 days and within 90 days did not vary among the majority of hospitals.
      The finding of lower chronic obstructive pulmonary disease readmission rates than
      was previously estimated and the limited variation in these rates between
      hospitals suggests that the opportunity to reduce chronic obstructive pulmonary
      disease readmission risk is small. CHRONIC LUNG DISEASE: LOWER RISK OF
      READMISSION FOR LONDON-BASED PATIENTS: A managed reduction of hospital
      readmissions for London-based chronic lung disease patients may not be needed.
      Preventing hospital readmissions for patients with chronic obstructive pulmonary
      disease (COPD) is a key priority to improve patient care and limit costs.
      However, few data are available to determine and ultimately reduce the risk of
      readmission. Timothy Harries at King's College, London, and co-workers conducted
      a longitudinal study incorporating all COPD admissions into UK hospitals for
      20,932 patients registered at London general practitioners between 2006 and 2010.
      They found that 32% of patients were readmitted within a year, 17.8% within 90
      days and 10% within 30 days. Neither age nor geographical deprivation were useful
      predictors of readmission. These represent lower than estimated levels of
      readmission, suggesting there may be fewer opportunities to reduce the risk of
      readmission further.

PMID- 28450740
TI  - The centrosomal OFD1 protein interacts with the translation machinery and
      regulates the synthesis of specific targets.
AB  - Protein synthesis is traditionally associated with specific cytoplasmic
      compartments. We now show that OFD1, a centrosomal/basal body protein, interacts
      with components of the Preinitiation complex of translation (PIC) and of the
      eukaryotic Initiation Factor (eIF)4F complex and modulates the translation of
      specific mRNA targets in the kidney. We demonstrate that OFD1 cooperates with the
      mRNA binding protein Bicc1 to functionally control the protein synthesis
      machinery at the centrosome where also the PIC and eIF4F components were shown to
      localize in mammalian cells. Interestingly, Ofd1 and Bicc1 are both involved in
      renal cystogenesis and selected targets were shown to accumulate in two models of
      inherited renal cystic disease. Our results suggest a possible role for the
      centrosome as a specialized station to modulate translation for specific
      functions of the nearby ciliary structures and may provide functional clues for
      the understanding of renal cystic disease.

PMID- 28450743
TI  - Implications of cancer evolution for drug development.

PMID- 28450744
TI  - Bridging the translational innovation gap through good biomarker practice.

PMID- 28450745
TI  - Contrasting response of rainfall extremes to increase in surface air and dewpoint
      temperatures at urban locations in India.
AB  - Rainfall extremes are projected to increase under the warming climate. The
      Clausius-Clapeyron (C-C) relationship provides a physical basis to understand the
      sensitivity of rainfall extremes in response to warming, however, relationships
      between rainfall extremes and air temperature over tropical regions remain
      uncertain. Here, using station based observations and remotely sensed rainfall,
      we show that at a majority of urban locations, rainfall extremes show a negative
      scaling relationship against surface air temperature (SAT) in India. The negative
      relationship between rainfall extremes and SAT in India can be attributed to
      cooling (SAT) due to the monsoon season rain events in India, suggesting that SAT
      alone is not a good predictor of rainfall extremes in India. In contrast, a
      strong (higher than C-C rate) positive relationship between rainfall extremes and
      dew point (DPT) and tropospheric temperature (T850) is shown for most of the
      stations, which was previously unexplored. Subsequently, DPT and T850 were used
      as covariates for non-stationary daily design storms. Higher magnitude design
      storms were obtained under the assumption of a non-stationary climate. The
      contrasting relationship between rainfall extremes with SAT and DPT has
      implications for understanding the changes in rainfall extremes in India under
      the projected climate.

PMID- 28450746
TI  - Changes in North Atlantic Oscillation drove Population Migrations and the
      Collapse of the Western Roman Empire.
AB  - Shifts in the North Atlantic Oscillation (NAO) from 1-2 to 0-1 in four episodes
      increased droughts on the Roman Empire's periphery and created push factors for
      migrations. These climatic events are associated with the movements of the Cimbri
      and Teutones from 113-101 B.C., the Marcomanni and Quadi from 164 to 180 A.D.,
      the Goths in 376 A.D., and the broad population movements of the Migration Period
      from 500 to 600 A.D. Weakening of the NAO in the instrumental record of the NAO
      have been associated with a shift to drought in the areas of origin for the
      Cimbri, Quadi, Visigoths, Ostrogoths, Huns, and Slavs. While other climate
      indices indicate deteriorating climate after 200 A.D. and cooler conditions after
      500 A.D., the NAO may indicate a specific cause for the punctuated history of
      migrations in Late Antiquity. Periodic weakening of the NAO caused drought in the
      regions of origin for tribes in antiquity, and may have created a powerful push
      factor for human migration. While climate change is frequently considered as a
      threat to sustainability, its role as a conflict amplifier in history may be one
      of its largest impacts on populations.

PMID- 28450737
TI  - Writing, erasing and reading histone lysine methylations.
AB  - Histone modifications are key epigenetic regulatory features that have important
      roles in many cellular events. Lysine methylations mark various sites on the tail
      and globular domains of histones and their levels are precisely balanced by the
      action of methyltransferases ('writers') and demethylases ('erasers'). In
      addition, distinct effector proteins ('readers') recognize specific methyl
      lysines in a manner that depends on the neighboring amino-acid sequence and
      methylation state. Misregulation of histone lysine methylation has been
      implicated in several cancers and developmental defects. Therefore, histone
      lysine methylation has been considered a potential therapeutic target, and
      clinical trials of several inhibitors of this process have shown promising
      results. A more detailed understanding of histone lysine methylation is necessary
      for elucidating complex biological processes and, ultimately, for developing and
      improving disease treatments. This review summarizes enzymes responsible for
      histone lysine methylation and demethylation and how histone lysine methylation
      contributes to various biological processes.

PMID- 28450747
TI  - Accessible areas in ecological niche comparisons of invasive species: Recognized
      but still overlooked.
AB  - Understanding biological invasions is crucial for their control and prevention.
      Specially, establishing whether invasive species operate within the constraint of
      conservative ecological niches, or if niche shifts occur at all commonly as part
      of the invasion process, is indispensable to identifying and anticipating
      potential areas of invasion. Ecological niche modeling (ENM) has been used to
      address such questions, but improvements and debate in study design, model
      evaluation, and methods are still needed to mature this field. We reanalyze data
      for Gray Squirrels (Sciurus carolinensis), native to North America, but invasive
      in Europe. Our main finding was that, when the analysis extent is established
      carefully based on analogous sets of environmental conditions, all evidence of
      niche shifts disappears, suggesting that previous reports of niche shifts for
      this species are artifacts of methods and interpretation, rather than biological
      reality. Niche conservatism should be tested only within appropriate, similar,
      environmental spaces that are accessible to both species or populations being
      compared, thus avoiding model extrapolation related to model transfers. Testing
      for environmental similarity between native and invaded areas is critical to
      identifying niche shifts during species invasion robustly, but also in
      applications of ENM to understanding temporal dimensions of niche dynamics.

PMID- 28450748
TI  - Thyroid cancer: The thyroid cancer epidemic - overdiagnosis or a real increase?

PMID- 28450751
TI  - Adipose tissue: Macrophage retention inhibits beige adipogenesis in obesity.

PMID- 28450752
TI  - Parameters Governing the Formation of Photopolymerized Silica Sol-Gel Monoliths
      in PDMS Microfluidic Chips.
AB  - Although polydimethylsiloxane (PDMS) microfluidic chips provide an alternative to
      more expensive microfabricated glass chips, formation of monolithic stationary
      phases in PDMS is not a trivial task. Photopolymerized silica sol-gel monoliths
      were fabricated in PDMS based microfluidic devices using 3
      trimethoxysilylpropylmethacrylate (MPTMOS) and glycidyloxypropyltrimethoxysilane
      (GPTMOS). The monolith formation was optimized by identifying a suitable porogen,
      controlling monomer concentration, functional additives, salts, porogen, wall
      attachment methods, and rinsing procedures. The resulting monoliths were
      evaluated using scanning electron microscopy, image analysis, differential
      scanning calorimetry, and separation performance. Monoliths functionalized with
      boronic acid ligands were used for the separation of cis-diol containing
      compounds both in batch mode and in the microfluidic chip.

PMID- 28450753
TI  - New Evidence on Self-Affirmation Effects and Theorized Sources of Heterogeneity
      from Large-Scale Replications.
AB  - Brief, targeted self-affirmation writing exercises have recently been offered as
      a way to reduce racial achievement gaps, but evidence about their effects in
      educational settings is mixed, leaving ambiguity about the likely benefits of
      these strategies if implemented broadly. A key limitation in interpreting these
      mixed results is that they come from studies conducted by different research
      teams with different procedures in different settings; it is therefore impossible
      to isolate whether different effects are the result of theorized heterogeneity,
      unidentified moderators, or idiosyncratic features of the different studies. We
      addressed this limitation by conducting a well-powered replication of self
      affirmation in a setting where a previous large-scale field experiment
      demonstrated significant positive impacts, using the same procedures. We found no
      evidence of effects in this replication study and estimates were precise enough
      to reject benefits larger than an effect size of 0.10. These null effects were
      significantly different from persistent benefits in the prior study in the same
      setting, and extensive testing revealed that currently theorized moderators of
      self-affirmation effects could not explain the difference. These results
      highlight the potential fragility of self-affirmation in educational settings
      when implemented widely and the need for new theory, measures, and evidence about
      the necessary conditions for self-affirmation success.

PMID- 28450754
TI  - Fast Ecotoxicity Detection Using Biosensors.
AB  - The article provides information about a new device, AlgaTox developed in the R&D
      project sponsored by the Technology Agency (n.TA02030179) and patented in Czech
      Republic (CZ 305687). Its functionality is based on the use of biosensor, and its
      main advantage is fast response rate. The toxicity detection is achieved through
      precise measurement of green algae oxygen production dynamics after their
      exposure to light of wavelength of 680 nm. Clark sensor with a resolution of
      0.05% of the equilibrium oxygen concentrations and stability at a constant
      pressure and temperature of 0.1% of the equilibrium oxygen concentration at the
      24-h measurement is used for the oxygen detection. Laboratory testing of the
      device has been made using silver nitrate, substance with known inhibitory effect
      on algae. Real samples of aqueous soil extracts and waste sample from old dried
      up industrial tailing pond enriched with insecticide have been also tested. The
      values of oxygen production inhibition or stimulation determined with the new
      device in the evaluation of real samples were up to six times higher in
      comparison with the corresponding values of inhibition (stimulation) of growth
      rates determined by standard procedure.

PMID- 28450750
TI  - Environmental influences on ovarian dysgenesis - developmental windows sensitive
      to chemical exposures.
AB  - A woman's reproductive health and ability to have children directly affect
      numerous aspects of her life, from personal well-being and socioeconomic
      standing, to morbidity and lifespan. In turn, reproductive health depends on the
      development of correctly functioning ovaries, a process that starts early during
      fetal life. Early disruption to ovarian programming can have long-lasting
      consequences, potentially manifesting as disease much later in adulthood. A
      growing body of evidence suggests that exposure to chemicals early in life,
      including endocrine-disrupting chemicals, can cause a range of disorders later in
      life, such as those described in the ovarian dysgenesis syndrome hypothesis. In
      this Review, we discuss four specific time windows during which the ovary is
      particularly sensitive to disruption by exogenous insults: gonadal sex
      determination, meiotic division, follicle assembly and the first wave of follicle
      recruitment. To date, most evidence points towards the germ cell lineage being
      the most vulnerable to chemical exposure, particularly meiotic division and
      follicle assembly. Environmental chemicals and pharmaceuticals, such as
      bisphenols or mild analgesics (including paracetamol), can also affect the
      somatic cell lineages. This Review summarizes our current knowledge pertaining to
      environmental chemicals and pharmaceuticals, and their potential contributions to
      the development of ovarian dysgenesis syndrome. We also highlight knowledge gaps
      that need addressing to safeguard female reproductive health.

PMID- 28450755
TI  - Phase behaviour of a continuous shouldered well model fluid. A grand canonical
      Monte Carlo study.
AB  - The phase behavior of the continuous shouldered well model fluid proposed by
      Franzese [J. Mol. Liq. 136 (2007) 267] was examined using the Monte Carlo
      computer simulations in the grand canonical ensemble. The essential parts of the
      vapour-liquid and liquid-liquid coexistence envelopes were obtained. The Widom
      lines departing from coexistence envelopes were calculated using maxima of the
      fluctuations of the number of particles as a function of chemical potential along
      various isotherms. The region embracing anomalies in the properties of the model
      was located using the approximate criterion that involves the excess pair
      entropy.. The temperature of maximum density line was built by performing
      canonical Monte Carlo simulations. Our results are consistent with previous
      results from molecular dynamics constant pressure-constant temperature
      simulations and provide wider insight into the phase behavior of the model by
      using the chemical potential as the external parameter.

PMID- 28450756
TI  - Optical changes of dentin in the near-IR as a function of mineral content.
AB  - The optical properties of human dentin can change markedly due to aging, friction
      from opposing teeth, and acute trauma, resulting in the formation of transparent
      or sclerotic dentin with increased mineral density. The objective of this study
      was to determine the optical attenuation coefficient of human dentin tissues with
      different mineral densities in the near-infrared (NIR) spectral regions from 1300
      2200 nm using NIR transillumination and optical coherence tomography (OCT). N=50
      dentin samples of varying opacities were obtained by sectioning whole extracted
      teeth into ~ 150 MUm transverse sections at the cemento-enamel junction or the
      apical root. Transillumination images were acquired with a NIR camera and
      attenuation measurements were acquired at various NIR wavelengths using a NIR
      sensitive photodiode. Samples were imaged with transverse microradiography (gold
      standard) in order to determine the mineral density of each sample.

PMID- 28450757
TI  - Selective removal of natural caries lesions from dentin and tooth occlusal
      surfaces using a diode-pumped Er:YAG laser.
AB  - Selective removal of caries lesions with high precision is best accomplished
      using lasers operating at high pulse repetition rates utilizing small spot sizes.
      Conventional flash-lamp pumped Er:YAG lasers are poorly suited for this purpose,
      but new diode-pumped solid-state (DPSS) Er:YAG lasers have become available
      operating at high pulse repetition rates. Microradiography was used to determine
      the mineral content of the demineralized dentin of 200-MUm thick sections with
      natural caries lesions prior to laser ablation. The purpose of this study was to
      explore the use of a DPSS Er:YAG laser for the selective removal of demineralized
      dentin and natural occlusal lesions on extracted teeth.

PMID- 28450758
TI  - Modelling the Ecological Comorbidity of Acute Respiratory Infection, Diarrhoea
      and Stunting among Children Under the Age of 5 Years in Somalia.
AB  - The aim of this study was to assess spatial co-occurrence of acute respiratory
      infections (ARI), diarrhoea and stunting among children of the age between 6 and
      59 months in Somalia. Data were obtained from routine biannual nutrition surveys
      conducted by the Food and Agriculture Organization 2007-2010. A Bayesian
      hierarchical geostatistical shared component model was fitted to the residual
      spatial components of the three health conditions. Risk maps of the common
      spatial effects at 1*1 km resolution were derived. The empirical correlations of
      the enumeration area proportion were 0.37, 0.63 and 0.66 for ARI and stunting,
      diarrhoea and stunting and ARI and diarrhoea, respectively. Spatially, the
      posterior residual effects ranged 0.03-20.98, 0.16-6.37 and 0.08-9.66 for shared
      component between ARI and stunting, diarrhoea and stunting and ARI and diarrhoea,
      respectively. The analysis showed clearly that the spatial shared component
      between ARI, diarrhoea and stunting was higher in the southern part of the
      country. Interventions aimed at controlling and mitigating the adverse effects of
      these three childhood health conditions should focus on their common putative
      risk factors, particularly in the South in Somalia.

PMID- 28450759
TI  - Sex in murky waters: algal-induced turbidity increases sexual selection in
      pipefish.
AB  - ABSTRACT: Algal-induced turbidity has been shown to alter several important
      aspects of reproduction and sexual selection. However, while turbidity has been
      shown to negatively affect reproduction and sexually selected traits in some
      species, it may instead enhance reproductive success in others, implying that the
      impact of eutrophication is far more complex than originally believed. In this
      study, we aimed to provide more insight into these inconsistent findings. We used
      molecular tools to investigate the impact of algal turbidity on reproductive
      success and sexual selection on males in controlled laboratory experiments,
      allowing mate choice, mating competition, and mate encounter rates to affect
      reproduction. As study species, we used the broad-nosed pipefish, Syngnathus
      typhle, a species practicing male pregnancy and where we have previously shown
      that male mate choice is impaired by turbidity. Here, turbidity instead enhanced
      sexual selection on male size and mating success as well as reproductive success.
      Effects from mating competition and mate encounter rates may thus override
      effects from mate choice based on visual cues, producing an overall stronger
      sexual selection in turbid waters. Hence, seemingly inconsistent effects of
      turbidity on sexual selection may depend on which mechanisms of sexual selection
      that have been under study. SIGNIFICANCE STATEMENT: Algal blooms are becoming
      increasingly more common due to eutrophication of freshwater and marine
      environments. The high density of algae lowers water transparency and reduces the
      possibility for fish and other aquatic animals to perform behaviors dependent on
      vision. We have previously shown that pipefish are unable to select the best
      partner in mate choice trials when water transparency was reduced. However, fish
      might use other senses than vision to compensate for the reduction in water
      transparency. In this study, we found that when fish were allowed to freely
      interact, thereby allowing competition between partners and direct contact
      between the fish, the best partner was indeed chosen. Hence, the negative effects
      of reduced water visibility due to algal blooms may be counteracted by the use of
      other senses in fish.

PMID- 28450761
TI  - To Make Room or Not to Make Room: Clients' Narratives About Exclusion and
      Inclusion of Spirituality in Family Therapy Practice.
AB  - This empirical article presents four narratives from an ongoing qualitative PhD
      project about spirituality and family therapeutic practice. Using case studies
      and narrative vignettes, the article presents client perspectives on being able
      to discuss their spirituality in therapy, and the repercussions when therapists
      exclude it. The article refers to current research and provides some reflections
      on how we can understand spirituality in the context of family therapeutic
      practice; therapists for holistic, cultural, and ethical reasons should
      acknowledge the client's spirituality. Therapists need to reflect on their own
      spirituality and how it may influence their relationships with clients.

PMID- 28450760
TI  - Psychological Assessment with the DSM-5 Alternative Model for Personality
      Disorders: Tradition and Innovation.
AB  - The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5)
      Section III Alternative Model for Personality Disorders (AMPD; APA, 2013)
      represents an innovative system for simultaneous psychiatric classification and
      psychological assessment of personality disorders (PD). The AMPD combines major
      paradigms of personality assessment and provides an original, heuristic,
      flexible, and practical framework that enriches clinical thinking and practice.
      Origins, emerging research, and clinical application of the AMPD for diagnosis
      and psychological assessment are reviewed. The AMPD integrates assessment and
      research traditions, facilitates case conceptualization, is easy to learn and
      use, and assists in providing patient feedback. New as well as existing tests and
      psychometric methods may be used to operationalize the AMPD for clinical
      assessments.

PMID- 28450762
TI  - Maternal Childhood Sexual Trauma, Child Directed Aggression, Parenting Behavior,
      and the Moderating Role of Child Sex.
AB  - Using propensity-matched controls, the present study examines the associations
      between maternal report of child-directed aggression and observed parenting
      behavior across early childhood for women with and without childhood sexual
      trauma histories. The moderating role of child sex was also examined. The sample
      (n=204) is from a longitudinal study of rural poverty exploring the ways in which
      child, family, and contextual factors shape development over time. After
      controlling for numerous factors including child and primary caregiver
      covariates, findings reveal that childhood sexual trauma is related to sensitive
      parenting behavior and child-directed aggression. Findings further revealed that
      child sex moderates the relation between sexual trauma history and maternal
      behavior towards children. Implications for interventions for mothers with
      childhood sexual trauma histories and directions for future study are proposed.

PMID- 28450763
TI  - 'What Does Donor Mean to a Four-Year-Old?': Initial Insights into Young
      Children's Perspectives in Solo Mother Families.
AB  - This study reports on the questions, thoughts and feelings of children aged 4-9
      conceived by donor insemination to single mothers. Fifty-one mothers and 47
      children from the same families were each administered a semi-structured
      interview. Mothers generally reported that while children either lack
      understanding, or have not yet been told, about their donor conception, they may
      be thinking and talking about the absence of a father. Most children did not
      mention either donor conception or father absence and reported positive feelings
      about their families and friendships. Possible explanations for the discrepancy
      between mothers' and children's reports are discussed.

PMID- 28450764
TI  - Medicinal Supply Has Remained as a Major Challenge for the Health Care in
      Ethiopia.

PMID- 28450765
TI  - Effect of Body Mass Index on Postoperative Complications in Beating Coronary
      Artery Surgery.
AB  - BACKGROUND: Body Mass Index (BMI) is considered as an important risk factor in
      cardiovascular surgery. We designed a historical cohort study for the evaluation
      of perioperative complications related to BMI in patients who underwent off-pump
      coronary artery bypass grafting (OPCAB). METHODS: We studied 1120 consecutive
      patients who underwent OPCAB between January 2008 and December 2011 in Imam Ali
      Hospital, Kermanshah, Iran. Patients were divided into four groups according to
      BMI: underweight/low BMI (< 18.5 kg/m2), healthy weight (between 18.5 kg/m2 and
      24.9 kg/m2), overweight/high BMI (between 25 kg/m2 and 30 kg/m2), and obese/very
      high BMI (> 30 kg/m2). RESULTS: In multivariable regression analysis, an
      important correlation between the underweight/low BMI group and mortality was
      observed (p=0.037). Postoperative stroke, postoperative atrial fibrillation (AF)
      and intra-aortic balloon pump (IABP) use were not associated with BMI. In linear
      regression analysis, significant correlations between low BMI, reintubation, ICU
      stay time and intubation time were found. Re-exploration for bleeding was
      significantly correlated with having a low or high BMI. CONCLUSION: Having a low
      BMI (which is association with malnutrition and respiratory muscles weakness) was
      significantly associated with reintubation, prolonged intubation time and ICU
      stay time. The obese group was also associated with postoperative atelectasia and
      fever.

PMID- 28450766
TI  - Coinheritance of B-Thalassemia and Sickle Cell Anaemia in Southwestern Nigeria.
AB  - BACKGROUND: Genes for haemoglobin S are found in high frequencies in Nigeria.
      However, there is little information on beta thalassemia in sickle cell anaemia
      in this population. The clinical presentation of HbS- beta thalassemia is
      enormously variable, ranging from an asymptomatic state to a severe disorder
      similar to homozygous sickle cell disease. MATERIALS AND METHODS: Haemoglobin A2
      and HbF were determined in sickle cell anaemia patients attending LAUTECH
      Teaching Hospital, Osogbo, by elution after electrophoresis and alkaline
      denaturation methods respectively. Haematological parameters were estimated using
      Sysmex KX-21N and percentage target cells using Leishman's staining technique.
      RESULTS: Exactly 6% f the SCA patients were found to have elevated HbA2 (>3.3%)
      and HbF (>1.3%). These patients also had normal erythrocyte indices, increased
      platelet count, a significantly higher HCT and an increased % target cell.
      CONCLUSION: These findings confirm that the frequency of beta thalassaemia in
      sickle cell patients in Nigeria is higher than previously thought. It is
      therefore important to consider the possibility of this variant in patients with
      sickle cell anaemia since their course may differ from that of patients with
      homozygous sickle cell anaemia.

PMID- 28450767
TI  - Status of Serum and Salivary Levels of Superoxide Dismutase in Type 2 Diabetes
      Mellitus with Oral Manifestations: A Case Control Study.
AB  - BACKGROUND: Type 2 Diabetes Mellitus is a very well known metabolic disorder that
      has reached epidemic proportions worldwide. Evidence suggests that oxidative
      stress increases in Diabetes Mellitus because of the excessive production of
      reactive oxygen species and an impaired antioxidant defence mechanism. This study
      estimated, compared and correlated the serum and salivary Superoxide dismutase
      levels in healthy subjects and subjects with Type 2 Diabetes Mellitus having oral
      manifestations. MATERIALS AND METHODS: In this study, serum and salivary
      Superoxide dismutase levels were estimated in 45 healthy subjects and 45 patients
      with Type 2 Diabetes Mellitus with oral manifestations. RESULTS: The mean serum
      and salivary Superoxide dismutase levels were significantly decreased in subjects
      with Type 2 Diabetes Mellitus with oral manifestations compared to the healthy
      subjects. Positive correlation in both healthy and diabetics was observed between
      serum and salivary samples. CONCLUSION: This study highlights that the abnormally
      high levels of oxidative stress in diabetics coupled with simultaneous decline in
      antioxidant defence mechanism results in complications in Diabetes mellitus. Thus
      exploring saliva for antioxidant markers that accurately reflect the redox status
      of the body is worthwhile.

PMID- 28450768
TI  - Bacteriological Quality of Street Foods and Antimicrobial Resistance of Isolates
      in Hawassa, Ethiopia.
AB  - BACKGROUND: Microbial contamination of ready-to-eat foods and beverages sold by
      street vendors and hawkers has become an important public health issue. In
      Ethiopia, health risks related to such kinds of foods are thought to be common.
      Thus, this study has tried to determine the bacteriological quality of ready- to-
      eat foods sold on streets. METHODS: A cross-sectional study was conducted on
      street foods in Hawassa City from May to September 2014. A total of 72 samples
      from six food items such as local bread ('ambasha' and 'kita'), raw fish, chilli
      ('awaze'), avocado and cooked potato were collected. Bacterial isolation, colony
      count and antimicrobial susceptibility testing were made following standard
      microbiological techniques. RESULTS: About 31% of the food samples showed total
      colony counts ranging from 1.7*105 to 6.7*106 colony-forming unit per gram
      (CFU/g) which is beyond the acceptable limits set for microbiological quality of
      ready- to -eat foods. The mean coliform and Enterobacteriaceae counts in raw
      fish, 'kita' and 'ambasha' were also higher than the limits. E.coli was the most
      frequent isolate (29.6%) followed by Salmonella species (12.7% and S.aureus
      (9.9%). All isolates were 100% sensitive to ciprofloxacin. About 89% of
      Salmonella sp was resistant to chloramphenicol. Alarmingly, 14.3% of S.aureus was
      resistant to vancomycin. CONCLUSION: This study confirmed considerable rate of
      contamination in street vended foods in Hawassa City. The identified foodborne
      bacteria and antibiotic resistance isolates could pose a public health problem in
      that locality. Therefore, regular inspection, health education and training of
      vendors on food handling and safety practices are recommended.

PMID- 28450769
TI  - Clinico-Pathological Patterns of Patients Who Underwent Orbital Exenteration in a
      Tertiary Eye Hospital of Nepal.
AB  - BACKGROUND: Orbital exenteration is a destructive procedure performed by removing
      all or part of the orbital contents along with entire eyeball. It is a procedure
      reserved for life threatening malignancies and some nonmalignant disorders which
      are not controlled by conservative management. METHODS: This is a retrospective
      study done on patients who underwent orbital exenteration at Tilganga Institute
      of Ophthalmology from1 January 2006- 30 in December 2014. RESULTS: The mean age
      of patients was 30 years (range 1-78), with male preponderance of 15(55.6%.
      Overall presenting duration of eye morbidity was 18 months (2 months-8.5 years).
      The most common presenting complaint was protrusion of eyeball1, 4(50%), primary
      site of tumor being intraocular in 10 patients (35.7%,) and total orbital
      exenteration was the most commonly performed type of surgery in 16(57.1%) out of
      27 patients. The most common etiology responsible for orbital exenteration, in
      pediatric age group of 9/27 patients (64.2%), was retinoblastoma whereas
      conjunctival squamous cell carcinoma (SCC)accounts for 5 patients (38.4%) in
      adults. Overall, the most common cause of orbital exenteration was retinoblastoma
      9(32.1%). CONCLUSION: The most common etiologies requiring orbital exenteration
      were retinoblastoma (in children and overall) and conjunctival squamous cell
      carcinoma (in adults), both diseases that could be addressed with less invasive
      treatment modality if detected earlier in the disease process. Designing strategy
      is important for early detection and treatment of these conditions, which would
      decrease disease morbidity and prognosis, potentially sparing sight and life.

PMID- 28450770
TI  - Prevalence, Pattern and Association of Pruritus with Quality of Life in Chronic
      Kidney Disease Patients Attending Kidney Care Centre, Ondo City, Southwest
      Nigeria.
AB  - BACKGROUND: Pruritus is a common cutaneous manifestation of chronic kidney
      disease (CKD). It is associated with poor sleep quality, anxiety and depression
      which may contribute to reduction in quality of life (QoL). Paying more attention
      to pruritus in CKD patients may improve their QoL, reduce kidney disease burden
      and mortality. This study determined the prevalence, pattern and association of
      pruritus with QoL in CKD patients. MATERIALS AND METHODS: This was a cross
      sectional descriptive study carried out in a Kidney Care Centre, Ondo City,
      Southwest Nigeria. The severity and intensity of pruritus and health-related QoL
      were assessed using validated instruments. P-value of < 0.05 was taken as
      significant. RESULTS: There were 91 CKD subjects with a male:female ratio of
      2.1:1. Sixty-nine (75.8%) of the CKD patients were not on dialysis while the
      remaining twenty-two (24.2%) were on maintenance hemodialysis (MHD). Thirty-nine
      (42.9%) of the CKD subjects had pruritus which was mild in 25(64.1%), moderate in
      8(20.5%) and severe in 6(15.4%). Pruritus was more common in MHD patients
      compared to predialysis CKD patients(50%vs40.6%) p = 0.47. The median pruritus
      intensity score was also higher in MHD patients compared to predialysis CKD
      patients (40vs30) p = 0.51. There was no significant association between gender,
      age, aetiology of CKD, stage of CKD and pruritus. There was a significant
      correlation between QoL score and pruritus intensity. (p = < 0.001, r = 0.56).
      CONCLUSION: Pruritus was common among our CKD subjects and it was not
      significantly associated with age, gender, stage or etiology of CKD. There was a
      significant association between impaired QoL and pruritus intensity.

PMID- 28450772
TI  - A Randomized Controlled Trial Study on the Effect of Adding Dexmedetomidine to
      Bupivacaine in Supraclavicular Block Using Ultrasound Guidance.
AB  - BACKGROUND: The benefits of regional anesthetic techniques are well established.
      Use of additives to local anesthetics can prolong these benefits. The aim of this
      study was to find out the effect of adding dexmedetomidine to bupivacaine for
      supraclavicular block. METHODS: In this randomized, double-blind study, 70 ASA I
      & II patients of either sex undergoing elective surgeries on the upper limb were
      given supraclavicular block under ultrasound guidance. Group C (n=35) received 38
      mL 0.25% bupivacaine + 2mL normal saline and group D received 38 mL 0.25%
      bupivacaine + 1 ug/kg dexmedetomidine (2mL). Patients were observed for, onset of
      motor and sensory block, duration of motor and sensory block, duration of
      analgesia, sedation score, hemodynamic changes and any adverse events. RESULTS:
      In group D, the onset was faster (P< 0.001), durations of sensory and motor block
      duration of and analgesia were prolonged as compared to group C (P <
      0.0001).There was a significant drop in heart rate (HR) from the baseline in
      group D (P < 0.05) at 30, 60, 90 and 120 min. However, none of the patients
      dropped HR below 50/min. Mean Arterial Pressure (MAP) remained unaffected. The
      patients in group D were more effectively sedated than those in group C (P <
      0.05). No adverse event was reported in either group. CONCLUSION: Dexmedetomidine
      as adjuvant to bupivacaine in supraclavicular block resulted in faster action,
      prolonged motor and sensory block, prolonged analgesia with hemodynamic stability
      and adequate sedation.

PMID- 28450771
TI  - In Vitro Antifungal Susceptibility of Environmental Isolates of Cryptococcus spp.
      from the West Region of Cameroon.
AB  - BACKGROUND: Cryptococcus neoformans is responsible of cryptococcosis, a life
      threatening infection that affects healthy and immunocompromised individuals. It
      is the first cause of adult acute meningitis in some sub-Saharan African
      countries with a mortality rate of about 100% in cases of inappropriate therapy.
      This study aimed at examining the occurrence and the antifungal patterns of
      Cryptococcus isolates from pigeon droppings and bat guanos in the west region of
      Cameroon. METHODS: A total of 350 samples were randomly collected from three
      selected localities of west region of Cameroon. The identification was performed
      based on capsule production assessed by Indian ink preparation. Additional tests
      performed were urea broth, glycine and tryptophan assimilation tests. The
      antifungal susceptibility test was performed by the broth microdilution method.
      RESULTS: Mycological analysis led to the identification of 98 isolates, of which
      57 isolates of C. neoformans var. gattii and 41 isolates of C. neoformans var.
      neoformans. All the isolates showed resistance to antifungals tested except
      nystatin which showed MIC mean values ranging between 0.5 ug/mL and 0.65 ug/mL.
      CONCLUSION: The prevalence of C. neoformans in pigeons and bats excreta in the
      west region of Cameroon is 28.57 %. C. neoformans var. gattii and C. neoformans
      var. neoformans are the main serotypes. Isolates found to be resistant to
      fluconazole and ketoconazole. Our results emphasize the need for further study on
      the molecular epidemiology in comparison with clinical isolates.

PMID- 28450773
TI  - McMurray's Test and Joint Line Tenderness for Medial Meniscus Tear: Are They
      Accurate?
AB  - BACKGROUND: Meniscus tears are the most common injury of the knee. The McMurray's
      test and Joint line tenderness for diagnosing meniscus tear have been widely
      tested, but results reported by different authors vary. The wide variations
      reported have an impact on clinical decision concerning whether to go for other
      diagnostic tests before going for diagnostic arthroscopy, which is considered as
      the gold standard.The purpose of this study was to determine the diagnostic value
      of Joint line tenderness and McMurray's test, as clinical signs, to diagnose
      underlying medial meniscus tears. METHODS: This was a prospective observational
      study done in Tribhuwan University Teaching Hospital. Patients undergoing knee
      arthroscopy were included in the study period of one year (from February 2011 to
      January 2012). Each patient was clinically examined with McMurray's test and
      joint line tenderness. The findings were then matched by the arthroscopic
      findings. The sensitivity, specificity, positive predictive value, negative
      predictive value and accuracy were then calculated. RESULTS: The sensitivity,
      specificity, positive predictive value , negative predictive value and accuracy
      for medial joint line tenderness in diagnosing medial meniscus tear were 50%,
      61.7%, 51.8%, 60% and 56.45% respectively. The result was insignificant (p
      value=0.352). The sensitivity, specificity, positive predictive value, negative
      predictive value and accuracy for McMurray's test for diagnosing medial meniscus
      tear were 54%, 79%, 68% , 67.50% and 67.74% respectively. The result was
      significant (p value=0.007). CONCLUSION: Clinical tests like McMurray and joint
      line tenderness have low diagnostic value when applied individually. They may be
      useful when combined together with the background of clinical history. The
      decision to scope the knee should not be solely taken on the results of clinical
      tests.

PMID- 28450774
TI  - Combined Effects of Medicinal Plants on Induced Upper Gastrointestinal Tract
      Injury in Wistar Rats.
AB  - BACKGROUND: Herbal medicines are now recently used as treatment options. This
      study was conducted to determine the effect of the combination therapy of
      medicinal herbs in the treatment of induced gastrointestinal injury among albino
      wistar rats. METHODS: A total of 60 Albino Wistar rats of both sexes weighing
      between 130g-150g were used. The control groups which consisted of negative
      control groups received 1ml of normal saline while the positive control group was
      given 20mg/kg of indomethacin and sacrificed after 6 hours. Those in the test
      group were given 20mg/kg of indomethacin, treated in different doses of single
      and combined extracts of Allium sativum, Brassica oleracea and Aloe barbadensis
      at 100mg/kg, 200mg/kg and 300mg/kg body weights, twice daily for 8 days and
      sacrificed. RESULTS: There was no visible sign of ulceration or perforation
      observed on the stomach and duodenum when compared with the control. The
      combination of all three plant extracts at different concentrations ranging from
      100 - 300mg/kg cleared all visible ulcers and perforations on the stomach of
      wistar rats. Similarly, all ulcers in the duodenum of indomethacin induced wistar
      rats were cleared by the combination of the three extracts. The sections of rat
      stomach and duodenum given 100mg/kg herbal cocktail and indomethacin showed
      normal mucosa. CONCLUSIONS: A mixture of the three herbs at 300mg/kg was better
      in healing gastric and duodenal ulcers. The mixture of the three plants extracts
      exhibit good anti-ulcer activity that warrants further studies.

PMID- 28450775
TI  - Assessment of Diarrheal Disease Prevalence and Associated Risk Factors in
      Children of 6-59 Months Old at Adama District Rural Kebeles, Eastern Ethiopia,
      January/2015.
AB  - BACKGROUND: Diarrheal disease is the commonchildhood illness and a leading killer
      of children aged under 5 years, especially in developing countries like Ethiopia.
      The aim of this study was to assess the prevalence of diarrheal disease and
      associated risk factors among children of 6-59 months old at Adama district rural
      kebeles, Eastern Ethiopia. METHODS: Community based cross sectional study design
      was conducted in January/2015. Descriptive method was used to describe study
      variables quantitatively and explanatory method to identify the effect of
      determinant factors on diarrheal disease occurrence. A single population
      proportion sample size formula was applied. Random sampling procedure was used by
      lottery method to select five kebeles and 442 house-holds. Data was collected by
      using pretested, structured questionnaires through interview and observational
      checklist by trained data collectors. Double entry was made to epi-info 3.5.3 and
      & transferred to SPSS20 for analysis. RESULT: The two weeks' period prevalence of
      diarrheal disease in children aged 6 to59 months was 14.7%; 95%CI [11.5-18.1].
      mother/caregiver who did not practice hand washing during the critical time was
      the only factor identified to be significantly associated with AOR=2.2; 95%CI
      [1.0-4.7] for the child hood diarrheal disease occurrence at Adama distict rural
      kebeles. CONCLUSION: Diarrheal disease prevalence is changed by child's caregiver
      hand washing practice during critical time. Health education for child's
      caregiver on hand washing practice during critical time is an important
      intervention for the prevention of diarrheal disease prevalence among children.

PMID- 28450776
TI  - Brainstem Anesthesia after Retrobulbar Block: A Case Report and Review of
      Literature.
AB  - BACKGROUND: Retro-bulbar anesthesia is one of the most common regional blocks
      used for intraocular surgeries. Complications associated with regional blocks may
      be limited to the eye or may be systemic. CASE REPORT: After a retro-bulbar block
      for glaucoma surgery, a 60-year-old man developed loss of consciousness, apnea
      with hypotension and bradycardia-features of brainstem anesthesia. We present the
      clinical features, treatment and comments on how to prevent the problem as well
      as a review of the literature on reported cases. CONCLUSION: Although it is rare,
      treating physicians should be aware of the potentially lethal consequences of
      retro-bulbar block, understand measures to reduce the risks and early recognition
      and treatment. Facilities where ophthalmic surgeries are performed under local
      anesthesia should be properly equipped and staffed for advanced resuscitation.

PMID- 28450777
TI  - Rare Locations of Epidermoid Cyst: Case Reports and Review.
AB  - BACKGROUND: Epidermoid cysts are benign lesions encountered throughout the body.
      Eighty percent of epidermoid cyst seen in ovaries and testicles, whereas in head
      and neck region they account for only 1.6-7.0%. 1.6% of epidermoid cysts occur in
      oral cavity and they account for 0.01% of all the oral cavity cysts. CASE
      DETAILS: Two case reports of epidermoid cyst has been discussed. One patient
      reported with well defined swelling in the right lower one third of the face,
      another one in the upper lip. Initially the cases were diagnosed as Lipoma and
      salivary adenoma respectively but histologically they turned out to be epidermoid
      cyst. Hence, we aim at highlighting the differential diagnosis pertaining to the
      anatomical location. The PubMed database search made on January 2016 yielded 674
      articles of epidermoid cyst in the head and neck region. In that there is only
      one case reported occuring in the lower one third of face. In the current report,
      we outline the second case of epidermoid cyst localized to the right mandibular
      body region without bone involvement. Another case in our report was localized in
      the upper lip. In the literature totally seven cases were reported till now
      occurring in the lip. CONCLUSION: Although epidermoid cysts are rarely
      encountered in the oral cavity, the possibility that they may occur warrants the
      need for successful management to avoid misdiagnosis.

PMID- 28450778
TI  - An Examination of Kindergarten Oral Language for African American Students: Are
      There Meaningful Differences in Comparison to Peers?
AB  - Understanding differences in oral language abilities is vital, particularly for
      children from low-income homes and minority children who are at an increased risk
      for academic failure because of differences or deficits in language use or
      exposure before they enter school. The purpose of this study was to investigate
      oral language performance, including receptive and expressive vocabulary,
      grammar, and sentence imitation, among a diverse group of kindergarten students
      (n = 503). Using hierarchical linear modeling, we examined the contributions of
      student race, African American or non-African American, student socioeconomic
      status (SES), and schoolwide SES to oral language performance. In separate
      analyses, we found significant absolute effects of both race and individual SES.
      However, when analyzed simultaneously, only race was a significant predictor for
      all measures. We also found that both identification as African American and
      schoolwide SES were significant predictors of oral language performance. We
      discuss implications for practice and future research.

PMID- 28450779
TI  - Clinical differences among the elderly admitted to the emergency department for
      accidental or unexplained falls and syncope.
AB  - It is difficult to distinguish unexplained falls (UFs) from accidental falls
      (AFs) or syncope in older people. This study was designed to compare patients
      referred to the emergency department (ED) for AFs, UFs or syncope. Data from a
      longitudinal study on adverse drug events diagnosed at the ED (ANCESTRAL-ED) in
      older people were analyzed in order to select cases of AF, syncope, or UF. A
      total of 724 patients (median age: 81.0 [65-105] years, 66.3% female) were
      consecutively admitted to the ED (403 AF, 210 syncope, and 111 UF). The number of
      psychotropic drugs was the only significant difference in patients with AF versus
      those with UF (odds ratio [OR] 1.44; 95% confidence interval 1.17-1.77). When
      comparing AF with syncope, female gender, musculoskeletal diseases, dementia, and
      systolic blood pressure >110 mmHg emerged as significantly associated with AF (OR
      0.40 [0.27-0.58], 0.40 [0.24-0.68], 0.35 [0.14-0.82], and 0.31 [0.20-0.49],
      respectively), while valvulopathy and the number of antihypertensive drugs were
      significantly related to syncope (OR 2.51 [1.07-5.90] and 1.24 [1.07-1.44],
      respectively). Upon comparison of UF and syncope, the number of central nervous
      system drugs, female gender, musculoskeletal diseases, and SBP >110 mmHg were
      associated with UF (OR 0.65 [0.50-0.84], 0.52 [0.30-0.89], 0.40 [0.20-0.77], and
      0.26 [0.13-0.55]), respectively. These results indicate specific differences, in
      terms of demographics, medical/pharmacological history, and vital signs, among
      older patients admitted to the ED for AF and syncope. UF was associated with
      higher use of psychotropic drugs than AF. Our findings could be helpful in
      supporting a proper diagnostic process when evaluating older patients after a
      fall.

PMID- 28450780
TI  - New generation of electrochemical immunoassay based on polymeric nanoparticles
      for early detection of breast cancer.
AB  - Screening and early diagnosis are the key factors for the reduction of mortality
      rate and treatment cost of cancer. Therefore, sensitive and selective methods
      that can reveal the low abundance of cancer biomarkers in a biological sample are
      always desired. Here, we report the development of a novel electrochemical
      biosensor for early detection of breast cancer by using bioconjugated self
      assembled pH-responsive polymeric micelles. The micelles were loaded with
      ferrocene molecules as "tracers" to specifically target cell surface-associated
      epithelial mucin (MUC1), a biomarker for breast and other solid carcinoma. The
      synthesis of target-specific, ferrocene-loaded polymeric micelles was confirmed,
      and the resulting sensor was capable of detecting the presence of MUC1 in a
      sample containing about 10 cells/mL. Such a high sensitivity was achieved by
      maximizing the loading capacity of ferrocene inside the polymeric micelles. Every
      single event of binding between the antibody and antigen was represented by the
      signal of hundreds of thousands of ferrocene molecules that were released from
      the polymeric micelles. This resulted in a significant increase in the intensity
      of the ferrocene signal detected by cyclic voltammetry.

PMID- 28450781
TI  - Simple and effective label-free electrochemical immunoassay for carbohydrate
      antigen 19-9 based on polythionine-Au composites as enhanced sensing signals for
      detecting different clinical samples.
AB  - Carbohydrate antigen 19-9 (CA19-9) is an important biomarker for the early
      diagnosis and clinical monitoring of pancreatic cancer. Reliable, simple, and
      accurate methods for the detection of CA19-9 are still urgently needed. In this
      study, polythionine-Au composites (AuNPs@ PThi) were designed and prepared
      through one-pot reaction using HAuCl4 as the co-oxidant and raw material in
      thionine solution containing FeCl3 as the oxidant. AuNPs@PThi-immobilized glassy
      carbon electrode was used as a sensitive redox probe for electrochemical
      interface. AuNPs@PThi not only favored the amplification of electrochemical
      signals but also facilitated excellent environmental friendliness for bioassay.
      Maximizing the electrochemical properties of AuNPs@PThi, an effective label-free
      electrochemical immunoassay for the ultrasensitive and reliable detection of CA19
      9 was developed. Under optimal conditions, the linear range of the proposed
      immunosensor was estimated to range from 6.5 to 520 U/mL, with a detection limit
      of 0.26 U/mL at a signal-to-noise ratio of 3. The prepared immunosensor for CA19
      9 detection showed high sensitivity, stability, and reproducibility. Furthermore,
      the fabricated immunosensor based on AuNPs@PThi can effectively detect and
      distinguish clinical serum samples of pancreatic cancer and normal control with
      accuracy and convenience.

PMID- 28450782
TI  - Gold nanorod-based poly(lactic-co-glycolic acid) with manganese dioxide core
      shell structured multifunctional nanoplatform for cancer theranostic
      applications.
AB  - Recently, photothermal therapy has become a promising strategy in tumor
      treatment. However, the therapeutic effect was seriously hampered by the low
      tissue penetration of laser. Therefore, in this study, radiofrequency (RF) with
      better tissue penetration was used for tumor hyperthermia. First, one type of
      gold nanorods (AuNRs) suitable for RF hyperthermia was selected. Then,
      poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with AuNRs and
      docetaxel (DTX) (PLGA/AuNR/DTX) NPs were constructed. Finally, manganese dioxide
      (MnO2) ultrathin nanofilms were coated on the surfaces of PLGA/AuNR/DTX NPs by
      the reduction of KMnO4 to construct the PLGA/AuNR/DTX@MnO2 drug delivery system.
      This drug delivery system can not only be used for the combined therapy of
      chemotherapy and RF hyperthermia but can also produce Mn2+ to enable magnetic
      resonance imaging. Furthermore, the RF hyperthermia and the degradation of MnO2
      can significantly promote the controlled drug release in a tumor region. The in
      vitro and in vivo results suggested that the PLGA/AuNR/DTX@MnO2 multifunctional
      drug delivery system is a promising nanoplatform for effective cancer theranostic
      applications.

PMID- 28450783
TI  - Vancomycin-modified Fe3O4@SiO2@Ag microflowers as effective antimicrobial agents.
AB  - Nanomaterials combined with antibiotics exhibit synergistic effects and have
      gained increasing interest as promising antimicrobial agents. In this study,
      vancomycin-modified magnetic-based silver microflowers (Van/Fe3O4@SiO2@Ag
      microflowers) were rationally designed and prepared to achieve strong
      bactericidal ability, a wide antimicrobial spectrum, and good recyclability. High
      performance Fe3O4@SiO2@Ag microflowers served as a multifunction-supporting
      matrix and exhibited sufficient magnetic response property due to their 200 nm
      Fe3O4 core. The microflowers also possessed a highly branched flower-like Ag
      shell that provided a large surface area for effective Ag ion release and
      bacterial contact. The modified-vancomycin layer was effectively bound to the
      cell wall of bacteria to increase the permeability of the cell membrane and
      facilitate the entry of the Ag ions into the bacterium, resulting in cell death.
      As such, the fabricated Van/Fe3O4@SiO2@Ag microflowers were predicted to be an
      effective and environment-friendly antibacterial agent. This hypothesis was
      verified through sterilization of Gram-negative Escherichia coli and Gram
      positive methicillin-resistant Staphylococcus aureus, with minimum inhibitory
      concentrations of 10 and 20 MUg mL-1, respectively. The microflowers also showed
      enhanced effect compared with bare Fe3O4@SiO2@Ag microflowers and free-form
      vancomycin, confirming the synergistic effects of the combination of the two
      components. Moreover, the antimicrobial effect was maintained at more than 90%
      after five cycling assays, indicating the high stability of the product. These
      findings reveal that Van/Fe3O4@SiO2@Ag microflowers exhibit promising
      applications in the antibacterial fields.

PMID- 28450784
TI  - Chitosan nanoparticle-based delivery of fused NKG2D-IL-21 gene suppresses colon
      cancer growth in mice.
AB  - Nanoparticles can be loaded with exogenous DNA for the potential expression of
      cytokines with immune-stimulatory function. NKG2D identifies major
      histocompatibility complex class I chain-related protein in human and retinoic
      acid early induced transcript-1 in mouse, which acts as tumor-associated
      antigens. Biologic agents based on interleukin 21 (IL-21) have displayed
      antitumor activities through lymphocyte activation. The NKG2D-IL-21 fusion
      protein theoretically identifies tumor cells through NKG2D moiety and activates T
      cells through IL-21 moiety. In this study, double-gene fragments that encode the
      extracellular domains of NKG2D and IL-21 genes were connected and then inserted
      into the pcDNA3.1(-) plasmid. PcDNA3.1-dsNKG2D-IL-21 plasmid nanoparticles based
      on chitosan were generated. Tumor cells pretransfected with dsNKG2D-IL-21 gene
      nanoparticles can activate natural killer (NK) and CD8+ T cells in vitro. Serum
      IL-21 levels were enhanced in mice intramuscularly injected with the gene
      nanoparticles. DsNKG2D-IL-21 gene nanoparticles accumulated in tumor tissues
      after being intravenously injected for ~4-24 h. Treatment of dsNKG2D-IL-21 gene
      nanoparticles also retarded tumor growth and elongated the life span of tumor
      bearing mice by activating NK and T cells in vivo. Thus, the dsNKG2D-IL-21 gene
      nanoparticles exerted efficient antitumor activities and would be potentially
      used for tumor therapy.

PMID- 28450785
TI  - Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the
      performance of cardiac constructs.
AB  - Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for
      cardiomyocyte growth and function. However, it remains to be elucidated whether
      CNT nanostructures can promote cell-cell integrity and facilitate the formation
      of functional tissues in 3-D hydrogels. Here, single-walled CNTs were
      incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which
      improved mechanical and electrical properties. The incorporation of CNTs (up to 1
      wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and
      elongation. Through the use of immunohistochemical staining, transmission
      electron microscopy, and intracellular calcium-transient measurement, the
      incorporation of CNTs was found to improve cell alignment and assembly
      remarkably, which led to the formation of engineered cardiac tissues with
      stronger contraction potential. Importantly, cardiac tissues based on CNT/Col
      hydrogels were noted to have better functionality. Collectively, the
      incorporation of CNTs into the Col hydrogels improved cell alignment and the
      performance of cardiac constructs. Our study suggests that CNT/Col hydrogels
      offer a promising tissue scaffold for cardiac constructs, and might serve as
      injectable biomaterials to deliver cell or drug molecules for cardiac
      regeneration following myocardial infarction in the near future.

PMID- 28450786
TI  - Hypertriglyceridemia, an important and independent risk factor for acute
      pancreatitis in patients with type 2 diabetes mellitus.
AB  - PURPOSE: Acute pancreatitis (AP) is a frequent inflammatory disease of the
      pancreas with multiple causes, among which high triglyceride (TG) level is the
      most common. The main purpose of this study has been to research the prevalence
      of AP in patients with diabetes mellitus (DM) and to underline the importance of
      hypertriglyceridemia (HTG) as a risk factor in triggering AP. The possible link
      between AP and glycemic control has been studied also, alongside some
      cardiovascular risk factors and long-term diabetes complications. PATIENTS AND
      METHODS: The patient cohort comprised 1,586 patients with DM, admitted to the
      Internal Medicine Clinic of Diabetes, Nutrition and Metabolic Disease within the
      Emergency Hospital in Timisoara between January and August 2016. Following a
      series of clinical and biological investigations, these patients were diagnosed
      with AP. The patients' antidiabetic treatment and chronic diabetes-related
      complications have also been recorded. RESULTS: The prevalence of pancreatitis in
      this group of patients was 3.7%. The presence of pancreatitis was associated with
      a higher HbA1c (8.5% vs 7.7%; P<0.001), fasting glycemia (167.5 vs 95 mg/dL;
      P<0.001), postprandial glycemia (244.5 vs 118 mg/dL; P<0.001), total cholesterol
      (256.5 vs 189.5 mg/dL; P<0.001), low-density lipoprotein cholesterol (LDLc)
      (208.7 vs 112.8 mg/dL; P<0.001), and TGs (495 vs 161 mg/dL; P<0.001). HDL
      cholesterol (HDLc) was found to be a significant protective factor against the
      risk of pancreatitis. On the contrary, high LDLc values were a significant risk
      factor for pancreatitis along with high non-HDLc and high TG values,
      respectively. CONCLUSION: The development of AP events in patients with DM is
      associated with unsatisfactory glycemic control, HTG, hypertension, and the
      presence and severity of DM chronic complications. In this study, the prevalence
      of AP events in patients with DM was 3.7%.

PMID- 28450787
TI  - Participation in physical activity and back pain among an elderly population in
      South Asia.
AB  - INTRODUCTION: Globally, chronic back pain is one of the most commonly encountered
      medical conditions among an elderly population with significant bearings on
      health, functional mobility and general well-being. OBJECTIVE: To estimate the
      burden of chronic back pain and its association with physical activity (PA) among
      population aged 50 years and above in Bangladesh, India, Nepal, Pakistan and Sri
      Lanka. METHODS: Cross-sectional data on 8502 men and women aged 50 years and
      above were collected from the World Health Survey (2002). Three forms of PA were
      considered - vigorous physical activity (VPA), moderate physical activity (MPA)
      and walking. Odds ratios (ORs) of the association between self-reported back pain
      and VPA, MPA and walking were calculated by using generalized estimating
      equations. RESULTS: The prevalence of back pain was, respectively, 64.8%, 19.8%,
      69.5%, 40.6% and 36.2% in Bangladesh, India, Nepal, Pakistan and Sri Lanka. No
      significant association between back pain and VPA was observed among men in any
      of the countries. In India, Pakistan and Sri Lanka, the odds of suffering from
      back pain were, respectively, 29%, 2.5 times and 59% higher among women who
      almost never took MPA. In India, taking MPA for few days a week and almost never
      was associated with, respectively, 38% (OR=1.38; 95% confidence interval
      [CI]=1.017-1.876) and 56% (OR=1.564; 95% CI=1.003-2.438) higher odds of reporting
      back pain. Walking almost never was also associated with, respectively, 83%
      (OR=1.829; 95% CI=1.14-2.934) and 2.9 times (OR=2.854; 95% CI=1.419-5.738) higher
      odds of reporting back pain among men in Nepal and Pakistan, respectively.
      CONCLUSION: Though the relationship was not consistent across sex and countries,
      results indicate that inadequate or nonparticipation can substantially increase
      the likelihood of suffering from back pain among an elderly population in this
      region. Further research is needed to better understand this relationship and the
      potential of exercised-based strategies to prevent and treat back pain among
      elderly persons.

PMID- 28450788
TI  - Effects of CYP2D6 and CYP3A5 polymorphisms on tamoxifen and its metabolites in
      Thai breast cancer patients.
AB  - PURPOSE: This study aimed to determine the effects of CYP2D6 and CYP3A5
      polymorphisms on the levels of tamoxifen (TAM) and its metabolites in the plasma
      of breast cancer patients. The protocol was designed to test the associations
      between CYP2D6, CYP3A5 genotypes and phenotypes (extensive metabolizer [EM],
      intermediate metabolizer [IM] and poor metabolizer [PM]) and TAM, N-desmethyl
      tamoxifen (NDMT), endoxifen (END) and 4-hydroxytamoxifen (4OHT) concentrations.
      PATIENTS AND METHODS: One hundred and thirty-four Thai breast cancer patients
      from the Thai Tamoxifen Project undergoing TAM treatment who met the
      inclusion/exclusion criteria were recruited. Plasma samples were assessed for the
      concentrations of TAM and its metabolites using high-performance liquid
      chromatography. The data are presented as actual values and metabolic ratios
      (MR). The hypotheses were tested using Kruskal-Wallis or Mann-Whitney U test,
      including the simple main effects analysis. RESULTS: The patients had stage 0-IV
      breast cancer. The mean age and body mass index were 51.6+/-11.6 years and 24.0+/
      4.3, respectively. Also, 53.0% of them were premenopausal, 10.4% were
      perimenopausal and 36.6% were postmenopausal, while 23.1% were CYP2D6-EM/CYP3A5
      EM and 20.9% carried only CYP2D6 and CYP3A5 incomplete alleles. The median
      concentrations of TAM, NDMT, END and 4OHT were 374.7 (interquartile range [IQR]
      230.2) ng/mL, 1,064.9 (IQR 599.6) ng/mL, 54.5 (IQR 52.5) ng/mL and 5.0 (IQR 3.1)
      ng/mL, respectively. MR (TAM-NDMT) and MR (NDMT-END) were statistically different
      (p=0.013 and p=0.014, respectively), while MR (4OHT-END) was not statistically
      different within the CYP2D6 phenotype (p=0.594). MR (TAM-4OHT) was not
      statistically different within the CYP2D6 phenotype (p=0.079), but it was
      potentially different from CYP3A5-PM (p=0.056). None of the MR was statistically
      different within the CYP3A5 phenotype. CONCLUSION: CYP2D6 polymorphisms appear to
      affect END concentration through an NDMT subpathway and potentially affect 4OHT
      concentrations through a 4OHT subpathway in CYP3A5-PM group.

PMID- 28450789
TI  - Body after baby: a pilot survey of genital body image and sexual esteem following
      vaginal birth.
AB  - OBJECTIVE: The aim of this study was to determine acceptability of the Vaginal
      Changes Sexual and Body Esteem (VSBE) scale for women post childbirth and explore
      the association between childbirth events and sexual/body esteem. DESIGN: This is
      a cross-sectional study within the Evaluating Maternal Recovery from Labor and
      Delivery study. SETTING: This study was conducted in a community setting.
      POPULATION: The study was conducted in women post first vaginal birth with birth
      events that posed risk factors for levator ani muscle tears. METHODS: Survey,
      magnetic resonance images of levator ani, and physical examination were the data
      collected 8 months postpartum. Birth variables were collected by hospital chart
      review. Descriptive analysis of VSBE response rates and distribution of responses
      was conducted. An exploratory analysis of the potential association of
      demographic, birth, clinical, and magnetic resonance image characteristics with
      VSBE scores was conducted. MAIN OUTCOME MEASURES: The outcome measure used in
      this study is VSBE scale. RESULTS: The majority of participants (97%) completed
      the scale, with responses to most questions skewed toward positive sexual/body
      esteem, with the exception of sexual enjoyment, where 38% indicated some
      interference due to genital changes. The scale showed high internal consistency
      (alpha =0.93). In the exploratory analysis of potential characteristics
      associated with VSBE, women with episiotomies had lower sexual/body esteem
      compared to those who did not (median VSBE scores 35 vs 42.5, P=0.01). Anal
      sphincter tear was not associated with sexual/body esteem (P=0.78). Additional
      study is indicated to further explore observed trends toward the association of
      severe levator ani tear, maternal age at childbirth, and forceps with VSBE
      scores. CONCLUSION: The VSBE is suitable for use to assess sexual/body esteem in
      women post childbirth. Most women in this sample did not indicate negative
      genital body image/sexual esteem. However, some indicated that the changes post
      birth negatively affected their sexual/body esteem, particularly those who had
      episiotomies.

PMID- 28450790
TI  - A revisit of the fetal foot length and fetal measurements in early pregnancy
      sonography.
AB  - OBJECTIVES: To present the fetal measurements in relation to the foot length at
      10-16 weeks gestation on antenatal ultrasound. MATERIALS AND METHODS: We reviewed
      the fetal measurements in 47 scans performed at 10-16 weeks gestation in women
      attending routine antenatal care. The fetal measurements and measurement ratios
      were examined in relation to the foot length. RESULTS: The fetal biparietal
      diameter, head circumference, abdominal circumference, femur length and foot
      length increase linearly with the gestational age at 10-16 weeks gestation. The
      correlation between fetal foot length and fetal biparietal diameter, head
      circumference, abdominal circumference and femur length are better than with the
      crown rump length. The femur length to foot length ratio and the femur length to
      abdominal circumference ratios increase with the gestational age in an inverse
      relationship throughout the same period. CONCLUSION: Fetal foot length is an
      accurate estimate of the gestational age in early pregnancy. Compared with crown
      rump length, the correlation between foot length and other fetal measurements is
      better. The fetal measurements ratios are gestational age dependent between 10-16
      weeks. Gestational age specific ratio should be used in this period.

PMID- 28450791
TI  - A case report of central toxic keratopathy in a patient post TransPRK (followed
      by corneal collagen cross-linking).
AB  - PURPOSE: The purpose of this article is to report a case of central toxic
      keratopathy in a patient post transepithelial photorefractive keratectomy
      (TransPRK), followed immediately by corneal collagen cross-linking. METHODS: This
      article describes the case of a 26-year-old male after bilateral aberration-free,
      TransPRK laser (Schwind Amaris 750S). The procedure was performed for compound
      myopic astigmatism in November 2015, followed immediately by accelerated corneal
      collagen cross-linking for early keratoconus. RESULTS: From day 3 post-op, tear
      film debris underneath both contact lenses with corneal haze and early,
      progressive central anterior stromal opacity formation only in the left eye were
      noted. At 2 weeks post-op, the left eye was noted to have a significant hyperopic
      shift with central corneal thinning in the anterior stroma. A central anterior
      stromal dense opacity had formed in the left eye with the surrounding superficial
      stromal haze. As of month 2, the opacity gradually started to improve in size and
      density. The hyperopic shift peaked at 2 months and continued to improve, largely
      due to epithelial compensation with a gradual recovery of stromal thickness.
      CONCLUSION: The question remains as to what provokes the typical central corneal
      necrosis/thinning in central toxic keratopathy. We hypothesize that the space
      between the contact lens and the corneal surface post TransPRK is prone to a
      "pseudo-interface pathology" that could mimic diffuse lamellar keratitis-like
      pathology. Suboptimal lid hygiene, resulting in tear film combinations of
      bacteria, inflammatory cells, matrix metalloproteinases and other proteolytic
      enzymes, contributes to the degradation of vulnerable, exposed collagen stromal
      tissue post TransPRK or any surface corneal ablation. Refractive surgeons should
      maintain a healthy lid margin and tear film, especially in contact lens wearers,
      to prevent potential complications in refractive surgery procedures.

PMID- 28450792
TI  - Long-term outcomes of the Bankart and Latarjet repairs: a systematic review.
AB  - The most common surgical techniques for the treatment of recurrent anterior
      shoulder instability include the arthroscopic Bankart repair, the open Bankart
      repair and the open Latarjet procedure. The purpose of this study was to evaluate
      and compare the long-term outcomes following these procedures. A systematic
      review of modern procedures with a minimum follow-up of 5 years was completed.
      The objective outcome measures evaluated were post-operative dislocation and
      instability rate, the Rowe score, radiographic arthritis and complications.
      Twenty-eight studies with a total of 1652 repairs were analyzed. The estimated re
      dislocation rate was 15.1% following arthroscopic Bankart repair, 7.7% following
      open Bankart repair and 2.7% following Latarjet repair, with the comparison
      between arthroscopic Bankart and open Latarjet reaching statistical significance
      (p<0.001). The rates of subjective instability and radiographic arthritis were
      consistently high across groups, with no statistical difference between groups.
      Estimated complication rates were statistically higher in the open Latarjet
      repair (9.4%) than in the arthroscopic Bankart (0%; p=0.002). The open Latarjet
      procedure yields the most reliable method of stabilization but the highest
      complication rate. There are uniformly high rates of post-operative subjective
      instability symptoms and radiographic arthritis at 5 years regardless of
      procedure choice.

PMID- 28450793
TI  - Two-year follow-up study of a group-based diabetes medical nutrition therapy and
      motivational interviewing intervention among African American women.
AB  - OBJECTIVES: To assess the 2-year efficacy of a combined medical nutrition therapy
      and motivational interviewing (MI) pilot study intervention and factors that
      influenced long-term dietary self-care. RESEARCH DESIGN AND METHODS: Pilot study
      participants, African American women with type 2 diabetes, completed a 2-year
      follow-up study visit, including clinical assessments and completion of a dietary
      self-care questionnaire and a semi-structured interview. Wilcoxon signed-rank
      tests were used to evaluate differences between baseline and 2-year follow-up
      clinical and dietary self-care outcomes. Hierarchical coding was used to analyze
      semi-structured interviews and categorize facilitator and barrier themes into
      subthemes. Subthemes were quantified based on the number of subtheme-related
      comments. RESULTS: Among the 12 participants (mean age 57.1+/-5.7 years),
      improvements were observed for HbA1c (baseline: 10.25%; interquartile range
      [IQR]: 8.10, 11.72 and follow-up: 8.8%; IQR: 7.48,10.22), systolic blood pressure
      (baseline: 142 mm Hg; IQR: 134.25, 157.25 and follow-up: 127 mm Hg; IQR: 113.5,
      143.25), frequency of eating high-fat foods (baseline: 3.5 days; IQR: 2.75, 4.25
      and follow-up: 3 days; IQR: 2.5, 4.5), and of spacing carbohydrates throughout
      the day (baseline: 3 days; IQR: 3.0, 4.0 and follow-up: 4 days; IQR: 1.5, 4.5).
      There was a statistically significant decrease (p=0.04) in the frequency of fruit
      and vegetable intake (baseline: 4 days; IQR: 3.75, 7.0 and follow-up: 3.5 days;
      IQR: 2.75, 4.0). Dietary self-care barriers and facilitators included internal
      (eg, motivation) and external factors (eg, social support). Motivation (70
      comments) and lack of motivation (67 comments) were the most pervasive
      facilitator and barrier subthemes, respectively. CONCLUSION: Overall, diabetes
      related clinical and dietary self-care outcomes were improved following a
      combined medical nutritional therapy/MI intervention, and motivation played an
      important role in dietary self-care engagement. Future research is needed to
      assess the added benefit of MI in improving clinical and dietary self-care
      outcomes and to identify best strategies to support post-intervention dietary
      self-care engagement.

PMID- 28450794
TI  - Variation in rotavirus vaccine coverage by sub-counties in Kenya.
AB  - Rotavirus gastroenteritis is an important cause of childhood morbidity and
      mortality in Kenya. In July 2014, Kenya introduced the rotavirus vaccine into her
      national immunization program. Although immunization coverage is crucial in
      assessing the real-world impact of this vaccine, variability in the vaccine
      coverage across the country is likely to occur. In view of this, we estimated the
      extent of coverage for the rotavirus vaccine at two socio-economically different
      sub-counties using the administrative data. The findings indicate disparities in
      vaccine coverage and access between the sub-counties and, thus, underscore the
      need to strengthen immunization systems to facilitate timely, accessible, and
      equitable vaccine delivery across the country. Both sub-counties recorded high
      vaccine dropout, suggestive of poor utilization of the vaccine. In this regard,
      increased social mobilization is needed to encourage vaccine compliance and to
      enhance tracking of vaccine defaulters. While efforts to improve the accuracy of
      the administrative coverage estimates are crucial, vaccination coverage surveys
      will be needed to verify the administrative coverage data and help identify
      specific factors relating to rotavirus vaccine coverage in the country.

PMID- 28450795
TI  - Expression of surface and intracellular Toll-like receptors by mature mast cells.
AB  - Nowadays, more and more data indicate that mast cells play an important role in
      host defense against pathogens. That is why it is essential to understand the
      expression of Toll-like receptors (TLRs) by mast cells, because these molecules
      play particularly significant role in initiation host defense against
      microorganisms as they recognize both wide range of microbial pathogen-associated
      molecular patterns (PAMPs) and various endogenous damage-associated molecular
      patterns (DAMPs) released in response to infection. Therefore, we examined the
      constitutive expression of both surface and endosomal TLRs in rat native fully
      mature tissue mast cells. By the use of qRT-PCR we found that these cells express
      mRNAs for TLR2, TLR3, TLR4, TLR5, TLR7, and TLR9. The expression of TLR3, TLR4,
      TLR5, TLR7, and TLR9 transcripts were low and comparable and only the expression
      of TLR2 transcript was significant. By the use of flow cytometry technique, we
      clearly documented that mast cells express TLR2, TLR4, and TLR5 on cell surface,
      while TLR3, TLR7, and TLR9 proteins are located both on the cell membrane and
      intracellularly. The highest expression was observed for TLR5 and the lowest for
      surface TLR7. These observations undoubtedly indicate that mature tissue mast
      cells have a broad set of TLR molecules, thus can recognize and bind bacterial,
      viral, and fungal PAMPs as well as various endogenous molecules generated in
      response to infection.

PMID- 28450797
TI  - EGb761 attenuates depressive-like behaviours induced by long-term light
      deprivation in C57BL/6J mice through inhibition of NF-kappaB-IL-6 signalling
      pathway.
AB  - Our previous investigation found that Ginkgo extract EGb761 could attenuate the
      depressive-like behaviours induced by a single injection of lipopolysaccharide in
      mice. However, it has not been investigated whether EGb761 is effective on
      depressive-like behaviours induced by long-term light deprivation and whether its
      effects are associated with the inhibition of NF-kappaB-IL-6 signalling pathway.
      In this study, three groups (vehicle group, EGb761 low-dose group, and EGb761
      high-dose group) of C57BL/6J male mice were exposed to constant darkness for four
      weeks. The control mice remained on a 12 : 12 light-dark cycle. Depressive-like
      behaviours were evaluated by tail suspension test (TST), forced swim test (FST),
      and sucrose preference test (SPT). Spontaneous locomotor activity was evaluated
      by open field test (OFT). Levels of IL-6, IL-6 mRNA, NF-kappaB p65, phospho-NF
      kappaB p65, IkappaBalpha, and phospho-IkappaBalpha were measured using Elisa,
      western blotting, or PCR assays. NF-kappaB p65 DNA binding activity was evaluated
      using Chemi Transcription Factor Assay Kit. Results showed long-term light
      deprivation prolonged the immobile time in TST and FST, shortened the latency to
      immobility in FST, reduced spontaneous locomotor activity in OFT, decreased
      sucrose preference in SPT, and increased levels of IL-6, IL-6 mRNA, NF-kappaB
      p65, phospho-NF-kappaB p65, and phospho-IkappaBalpha in hippocampal tissue.
      EGb761 dose-dependently reversed the changes of the above parameters induced by
      long-term light deprivation, without affecting spontaneous locomotor activity. We
      conclude that EGb761 could attenuate the depressive-like behaviours and inhibit
      the NF-kappaB-IL-6 signalling pathway in a light-deprivation-induced mouse model
      of depression.

PMID- 28450796
TI  - Ellagic acid alleviates adjuvant induced arthritis by modulation of pro- and anti
      inflammatory cytokines.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology,
      but it is now clear that pro-inflammatory cytokines play a central role in its
      pathogenesis. Ellagic acid (EA) has a variety of biological activities including
      anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of the
      present study was to evaluate the potential effect of ellagic acid on the
      prevention and/or treatment of adjuvant induced arthritis (AIA) model in mice.
      Ellagic acid treatment was started one week before AIA induction and continued
      for three weeks after induction of AIA. Ellagic acid treatment significantly (p <
      0.01) inhibited foot paw oedematous swelling and attenuated AIA-associated
      pathology. Ellagic acid significantly (p < 0.01) reduced serum levels of pro
      inflammatory cytokines: interleukin 1beta (IL-1beta), tumor necrosis factor alpha
      (TNF-alpha), and interleukin 17 (IL-17). However, serum levels of IL-10 and
      interferon gamma (IFN-gamma) significantly increased (p < 0.01 and p < 0.05,
      respectively), while serum level of transforming growth factor beta (TGF-beta)
      did not significantly alter with EA treatment. In conclusion, these results
      suggest that EA attenuated AIA-associated pathology in the mouse model by
      downregulation of pro-inflammatory cytokines and upregulation of anti
      inflammatory cytokines.

PMID- 28450798
TI  - Elevated level of some chemokines in plasma of gastric cancer patients.
AB  - INTRODUCTION: Gastric cancer is one of the most common cancer-related causes of
      death. This is mainly due to the lack of good noninvasive method/biomarkers
      suitable for early-tumour diagnosis and planning of further therapy modalities.
      Chemokines play an important role in cancer progression and metastasis formation.
      In gastric cancer patients, clinical relevance of CXCL12 and CCL5 level has been
      postulated. AIM OF THE STUDY: Efforts were undertaken to examine whether expanded
      chemokine range may be relevant for evaluation of preoperative staging of gastric
      cancer patients. MATERIAL AND METHODS: Plasma from 66 gastric cancer patients and
      11 healthy controls was obtained, and CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL9, and
      CXCL10 levels were determined by flow cytometry FlexSet system. RESULTS: In
      gastric cancer patients' plasma an increased level of CCL2, CCL4, CCL5, CXCL8,
      CXCL9, and CXCL10 was observed. In the case of CCL2, CXCL9, and CXCL10, the
      chemokine levels correlated with advanced (III and IV in TNM classification)
      disease stage. In the case of CCL4, CCL5, and CXCL8, elevated levels were
      observed in all cancer patients in comparison to healthy donors. CONCLUSIONS: The
      accuracy of preoperative diagnosis in gastric cancer may include the monitoring
      of a wide range of chemokines in patients' plasma. Increased levels of chemokines
      may warn that the disease is more advanced than conventional diagnostic
      procedures suggest.

PMID- 28450799
TI  - The effect of hydrolysates of proteins from rice milk on the physiological
      response of enterocytes and on the adhesion of bacteria from healthy and allergic
      people - an in vitro study.
AB  - Designing an optimal diet requires knowledge of the biological activity of food
      products, particularly in relation to people with food allergies. The hypothesis,
      which constitutes the basis of this thesis, states that the peptides and
      glycopeptides released from proteins by enzymatic hydrolysis are able to change
      the quantity and quality of the human gastrointestinal ecosystem. Such substrates
      may interfere with adhesion to the intestinal epithelium microbiota and alter
      enterocytic metabolic activity. The aim of this study was to determine the effect
      of protein hydrolysates from rice milk substitute on gut epithelial cells and the
      intestinal microbiota of healthy people and ones suffering from an allergy to
      milk. The following experimental work applied systems that reflect the conditions
      occurring in the gastrointestinal tract.

PMID- 28450800
TI  - Assessment of interleukin-17A, C5a and RANTES for early diagnosis of neonatal
      sepsis - a preliminary study.
AB  - The aim of the present study was to investigate serum levels of novel markers:
      interleukin 17A (IL-17A), anaphylatoxin C5a and chemokine regulated upon
      activation normal T-cell expressed and secreted (RANTES) in neonates with
      clinically suspected early-onset neonatal sepsis (EONS), and to compare their
      values with those of non-infected neonates. Eighteen neonates with clinical signs
      and symptoms of EONS were enrolled in this study. Fifty healthy, non-infected
      neonates served as the control group. In all neonates serum levels of IL-17A, C5a
      and RANTES were measured by solid-phase sandwich enzyme-linked immunosorbent
      assay (ELISA). At the time of investigation serum levels of anaphylatoxin C5a
      were significantly higher in neonates with clinical symptoms of EONS than in non
      infected neonates (median 65.35 vs. 50.4 ng/ml, p = 0.034), whereas levels of
      RANTES were similar and levels of IL-17A were under detection limit of the
      method. Based on these preliminary results, serum levels of C5a may be a useful
      marker of inflammation in early onset neonatal sepsis. Because traditional
      methods of microbiological diagnostics in EONS are frequently unsuccessful, the
      search for an alternative laboratory biomarkers is of great clinical importance.
      Thus, there is a strong need for further studies evaluating usefulness of this
      anaphylatoxin in EONS diagnosis on a larger group of patients.

PMID- 28450801
TI  - No evidence of West Nile virus infection among Polish patients with encephalitis.
AB  - West Nile virus (WNV) infection usually causes mild febrile illness, but in a
      small proportion of patients it can lead to encephalitis. Epidemiological studies
      of WNV indicate fast spread of infection worldwide and in Europe, but there have
      been no comprehensive studies of WNV infection among encephalitis patients in
      Poland. Here we present the results of WNV RNA and anti-WNV testing in serum and
      cerebrospinal fluid (CSF) samples in 80 patients with the clinical diagnosis of
      viral encephalitis. WNV RNA was not detected in any of the analyzed samples. Anti
      WNV IgG and IgM were not present in CSF in any of the investigated patients, but
      anti-WNV IgM were unexpectedly detected in serum of 14 subjects. The latter
      represented false positive results are probably related to cross reactivity of
      antibodies. Although there was no evidence of WNV infection in any of our
      patients, epidemiological situation in the neighbouring countries warrants
      vigilance and appropriate measures, including introduction of specific diagnostic
      tools into clinical practice, seem necessary.

PMID- 28450802
TI  - Neutrophil to lymphocyte ratio is associated with proximal/middle segment of the
      LAD lesions in patients with ST segment elevation infarction.
AB  - INTRODUCTION: Neutrophil to lymphocyte ratio (NLR) was revaled to have a close
      relation with atherosclerotic cardiovascular disease. The relationship between
      NLR and culprit plaque localization has never been studied. AIM OF THE STUDY: To
      evaluate the association between NLR and unstable plaque localization of left
      anterior descending artery (LAD) in anterior miyocardial infarction patients.
      MATERIAL AND METHODS: Patients admitted to our hospital with acute anterior STEMI
      were included. Fifhy-eight patients who have single-vessel disease at LAD and
      their hematological parameters were analyzed retrospectively. Proximal segment of
      LAD lesions were groupped as Group I and mid segment of the LAD lesion groupped
      as Group II. The groups were compared according to their NLR and other
      parameters. RESULTS: Between group I (n = 41, mean age 52.5 +/-12.7) and group II
      (n = 17, mean ages 52.0 +/-10.8); NLR, were significantly higher in group I
      compared to the group II (6.9 +/-5.6 vs. 3.3 +/-2.0, p = 0.01). In group I, left
      ventricular ejection fraction (LVEF) was significantly lower (p = 0.02). In
      correlation analyzes, NLR was positively correlated with CK MB (r = 0.32, p =
      0.01) and negatively correlated with LVEF (r = -0.28, p = 0.03). CONCLUSIONS: The
      present study demonstrated that anterior myocardial infarction patients with high
      NLR had a greater possibility having proximal culprit lesion on the LAD.
      Therefore NLR can be used as a useful tool to culprit plaque localization in
      patients with acute miyocardial infarction patients.

PMID- 28450803
TI  - Diagnostic value of selected markers and apoptotic pathways for pancreatic
      cancer.
AB  - Pancreatic cancer occupies the fourth place as a cause of death from cancer, and
      the mortality rate is similar to the number of newly detected cases. Due to the
      late diagnosis, only 5-6% of patients with pancreatic cancer survive for five
      years. Given that early diagnosis is critical for improving patients' survival
      rates, there is an urgent need for the discovery and validation of new biomarkers
      with sufficient sensitivity and specificity to help diagnose pancreatic cancer
      early. Detection of serum tumor markers (CA19-9, CEA, CA125 and CA242) is
      conducive to the early diagnosis of pancreatic cancer. The combination of miR-16,
      miR-196a and CA19-9 plasma level was more effective, especially in early tumor
      screening. Furthermore, recent studies reported that mainly miR-21, miR-155 and
      miR-196 were dysregulated in IPMN (intraductal papillary mucinous neoplasms) and
      PanIN (pancreatic intraepithelial neoplasia) lesions, suggesting their usefulness
      as early biomarkers of these diseases. The reduced rate of apoptosis plays a
      crucial role in carcinogenesis, and it is one of the most important
      characteristics acquired by pancreatic cancer cells, which protects them from
      attack by the immune system and reduces the effectiveness of pharmacological
      treatment. This review summarizes the data concerning the clinical utility of
      selected biomarkers in pancreatic cancer patients. The review mainly focuses on
      the genetic aspects of signaling pathway disorders associated with apoptosis in
      the pathogenesis and diagnosis of pancreatic cancer.

PMID- 28450805
TI  - Endogenous antimicrobial factors in the treatment of infectious diseases.
AB  - Nowadays, a number of antibiotic-resistant bacteria strains is increasing. It is
      a serious clinical problem and poses a threat to the effectiveness of
      conventional antibiotic therapy. Thus, scientists are constantly seeking new
      alternatives for treatment of infectious diseases. There are some natural
      endogenous factors, which possess antimicrobial activities against a large number
      of microorganisms, including both Gram-positive and Gram-negative bacteria,
      viruses and fungi. These factors are present in all eukaryotic organisms and
      constitute an essential element of their immune system. A large number of in
      vitro and in vivo models have been used to show the activity of antimicrobial
      factors, and only few studies have been conducted on people. Results indicate
      that administration of these molecules is therapeutically beneficial. This review
      summarizes knowledge of selected endogenous antimicrobial agents, such as
      cathelicidins, defensins, histatins, lysozyme and lactoferrin. We also discuss
      potential uses of these factors in the treatment of infectious diseases.

PMID- 28450804
TI  - Dysregulation of signaling pathways associated with innate antibacterial immunity
      in patients with pancreatic cancer.
AB  - Disorders of innate antibacterial response are of fundamental importance in the
      development of gastrointestinal cancers, including pancreatic cancer. Multi
      regulatory properties of the Toll-like receptors (TLRs) (e.g., regulation of
      proliferation, the activity of NF-kappaB, gene transcription of apoptosis
      proteins, regulation of angiogenesis, HIF-1alpha protein expression) are used in
      experimental studies to better understand the pathogenesis of pancreatic cancer,
      for early diagnosis, and for more effective therapeutic intervention. There are
      known numerous examples of TLR agonists (e.g., TLR2/5 ligands, TLR6, TLR9) of
      antitumor effect. The direction of these studies is promising, but a small number
      of them does not allow for an accurate assessment of the impact of TLR expression
      disorders, proteins of these signaling pathways, or attempts to block or
      stimulate them, on the results of treatment of pancreatic cancer patients. It is
      known, however, that the expression disorders of proteins of innate antibacterial
      response signaling pathways occur not only in tumor tissue but also in peripheral
      blood leukocytes of pancreatic cancer patients (e.g., increased expression of
      TLR4, NOD1, TRAF6), which is one of the most important factors facilitating
      further tumor development. This review mainly focuses on the genetic aspects of
      signaling pathway disorders associated with innate antibacterial response in the
      pathogenesis and diagnosis of pancreatic cancer.

PMID- 28450806
TI  - MicroRNAs as regulators of drug abuse and immunity.
AB  - MicroRNAs (miRNAs) are 20-22 nucleotide non-coding RNAs that participate in gene
      regulation. They bind to 3'-untranslated regions of their mRNA targets,
      inhibiting the transcripts' translation and/or destabilizing them. Chronic drug
      abuse induces changes of miRNAs expression in the brain, which is thought to
      contribute to addictive behaviors. Lots of miRNAs have been identified to play
      critical roles in the development of drug addiction. Moreover, miRNAs have been
      shown to play critical roles in a broad array of biologic processes, including
      regulation of the cell cycle, oncogenic transformation, immune cell regeneration
      and differentiation, and psychiatry disorders. We hypothesized that chronic drug
      abuse leads to aberrant expression of several miRNAs, and then aberrant miRNAs
      influence the innate and adaptive immunity, especially differentiation and
      function of T cells and B cells, through down-regulated miRNAs' target gene
      expression. Characterization of miRNA actions is important and has high potential
      effect for the management of drug addiction and immunity diseases. miRNAs are
      potential biomarkers, and the modulation of their expression can be used for
      therapeutic purposes.

PMID- 28450807
TI  - Coronins and their role in immunological phenomena.
AB  - Coronins are a large family of proteins occurring in many eukaryotes. In mammals,
      seven coronin genes have been identified, evidencing that coronins 1 to 6 present
      classic coronin structure, while coronin 7 is a tandem coronin particle, without
      a spiral domain, although the best characterised coronin, in terms of both
      structure and function, is the mammalian coronin 1. It has been proven that they
      are related to regulation of actin dynamics, e.g. as a result of interaction with
      the complex of proteins Arp2/3. These proteins also modulate the activity of
      immune system cells, including lymphocyte T and B cells, neutrophils and
      macrophages. They are involved in bacterial infections with Mycobacterium
      tuberculosis, M. leprae and Helicobacter pylori and participate in the response
      to viral infections, e.g. infections of lymphocytic choriomeningitis virus (LCMV)
      and vesicular stomatitis Indiana virus (VSV). Also their involvement in
      autoimmune diseases such as lupus erythematosus has been recorded.

PMID- 28450808
TI  - Metformin exhibits the anti-proliferation and anti-invasion effects in
      hepatocellular carcinoma cells after insufficient radiofrequency ablation.
AB  - BACKGROUND: The mechanisms and prevention of progression of hepatocellular
      carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been
      preliminarily investigated, therefore, new strategy needs to be investigated to
      prevent the process. Whether metformin could be used to inhibit the growth of HCC
      after insufficient RFA and further prevent the progression of residual HCC
      remains unclearly. METHODS: MTT assay, colony formation assay and transwell assay
      were used to observe the cell viability, migration and invasion. Western blot and
      immunohistochemistry methods were used to observe the expression of proteins.
      Xenograft model was used to evaluate the growth of HCC cells in vivo. RESULTS:
      Metformin inhibited the enhanced proliferation, migration and invasion of HepG2
      and SMMC7721 cells after insufficient RFA (named as HepG2-H and SMMC7721-H).
      Metformin deregulated the expression of p-Akt in HepG2 and SMMC7721 cells after
      insufficient RFA through AMPK/PTEN pathway. HepG2-H cells also exhibited larger
      tumor size in vivo. Higher expression of Ki-67 and CD31 and lower expression of E
      cadherin were observed in HepG2-H tumors. Metformin blocked the enhanced growth
      of HepG2 cells in vivo after insufficient RFA. Metformin had no apparent toxicity
      on nude mice. CONCLUSIONS: Metfromin inhibited the growth of HCC cells after
      insufficient RFA, and may be used to prevent the progression of HCC after RFA.

PMID- 28450809
TI  - pATM and gammaH2AX are effective radiation biomarkers in assessing the
      radiosensitivity of 12C6+ in human tumor cells.
AB  - BACKGROUND: Tumour radiosensitivity would be particularly useful in optimizing
      the radiation dose during radiotherapy. The aim of the current study was to
      evaluate the potential value of phosphorylated H2AX (gammaH2AX) and ATM (pATM) in
      assessing 12C6+ radiosensitivity of tumour cells. METHODS: Human cervical
      carcinoma HeLa cells, hepatoma HepG2 cells, and mucoepidermoid carcinoma MEC-1
      cells were irradiated with different doses of 12C6+. The survival fraction was
      assayed with clonogenic survival method and the foci of gammaH2AX and pATM was
      visualized using immunocytochemical methods. Flow cytometry was used to assay
      gammaH2AX, pATM and the cell cycle. RESULTS: The survival fraction decreased
      immediately in dose-dependent manner, but in turn, significantly increased during
      24 h after 12C6+ irradiation. Both gammaH2AX and pATM foci accumulated linearly
      with doses and with a maximum induction at 0.5 h for gammaH2AX and 0.5 or 4 h for
      pATM, respectively, and a fraction foci kept for 24 h. The expression of
      gammaH2AX and pATM was in relation to cell cycle. The G0/G1 phase cells had the
      highest expression of gammaH2AX after 0.5 h irradiation and then decreased to a
      lower level at 24 h after irradiation. An obvious increase of pATM in G2/M phase
      was shown after 24 h of 2 and 4 Gy irradiation. The significant G2/M phase arrest
      was shown. There was a close relationship between the clonogenic survival and
      gammaH2AX and pATM expression both in timing and dose in response to 12C6+.
      CONCLUSIONS: The rate of gammaH2AX and pATM formation and loss may be an
      important factor in the response of cells to 12C6+. pATM and gammaH2AX are
      effective radiation biomarkers in assessing the radiosensitivity of 12C6+ in
      human tumor cells.

PMID- 28450811
TI  - Efficiency and productivity assessment of public hospitals in Greece during the
      crisis period 2009-2012.
AB  - BACKGROUND: This study is an initial effort to examine the dynamics of efficiency
      and productivity in Greek public hospitals during the first phase of the crisis
      2009-2012. Data were collected by the Ministry of Health after several quality
      controls ensuring comparability and validity of hospital inputs and outputs.
      Productivity is estimated using the Malmquist Indicator, decomposing the
      estimated values into efficiency and technological change. METHODS: Hospital
      efficiency and productivity growth are calculated by bootstrapping the non
      parametric Malmquist analysis. The advantage of this method is the estimation
      efficiency and productivity through the corresponding confidence intervals.
      Additionally, a Random-effects Tobit model is explored to investigate the impact
      of contextual factors on the magnitude of efficiency. RESULTS: Findings reveal
      substantial variations in hospital productivity over the period from 2009 to
      2012. The economic crisis of 2009 had a negative impact in productivity. The
      average Malmquist Productivity Indicator (MPI) score is 0.72 with unity
      signifying stable production. Approximately 91% of the hospitals score lower than
      unity. Substantial increase is observed between 2010 and 2011, as indicated by
      the average MPI score which fluctuates to 1.52. Moreover, technology change
      scored more than unity in more than 75% of hospitals. The last period (2011-2012)
      has shown stabilization in the expansionary process of productivity. The main
      factors contributing to overall productivity gains are increases in occupancy
      rates, type and size of the hospital. CONCLUSIONS: This paper attempts to offer
      insights in efficiency and productivity growth for public hospitals in Greece.
      The results suggest that the average hospital experienced substantial
      productivity growth between 2009 and 2012 as indicated by variations in MPI.
      Almost all of the productivity increase was due to technology change which could
      be explained by the concurrent managerial and financing healthcare reforms.
      Hospitals operating under decreasing returns to scale could achieve higher
      efficiency rates by reducing their capacity. However, certain social objectives
      should also be considered. Emphasis perhaps should be placed in utilizing and
      advancing managerial and organizational reforms, so that the benefits of
      technological improvements will have a continuing positive impact in the future.

PMID- 28450810
TI  - Reduced cardiac function and risk of venous thromboembolism in Asian countries.
AB  - Patients with reduced cardiac function are thought to have a higher risk of
      venous thromboembolism (VTE). Additionally, they are vulnerable to complications
      of pulmonary embolism (PE) as well as right heart failure (HF), which in return
      is supposed to increase the rate of mortality. Studies focusing on VTE in heart
      failure patients were rare in Asian countries before the 21st century. Nowadays,
      more and more data are becoming available in this field in Asia. It is already
      known that heart failure can increase the risk of VTE, but so far a consensus on
      this issue has not been reached for many years, not only in Asian countries but
      all over the world. This condition may be due to the detailed pathological
      advancement in Virchow's triad and some other theories. In clinical practice,
      VTE, especially PE is difficult to diagnose in patients with heart failure
      because of overlapping symptoms (e.g. cough and chest pain) and the elevation of
      laboratory markers (e.g. probrain natriuretic peptide (NT-proBNP) and D-dimer in
      both heart failure and VTE patients). Management of VTE in heart failure patients
      is also controversial because heart failure patients always have complications,
      such as renal failure and hepatic failure, which increase the risk of bleeding.
      In this study, we analyzed data from China, Japan, Korea, Singapore and India
      mainly to get a better understanding of the research progress in VTE in patients
      with heart failure. The aim of this review is to discuss the risk, incidence,
      advancement of diagnosis, management and prevention of VTE in patients with heart
      failure in Asian countries.

PMID- 28450812
TI  - Changing ethnic inequalities in mortality in New Zealand over 30 years: linked
      cohort studies with 68.9 million person-years of follow-up.
AB  - BACKGROUND: Internationally, ethnic inequalities in mortality within countries
      are increasingly recognized as a public health concern. But few countries have
      data to monitor such inequalities. We aimed to provide a detailed description of
      ethnic inequalities (Maori [indigenous], Pacific, and European/Other) in
      mortality for a country with high quality ethnicity data, using both standard and
      novel visualization methods. METHODS: Cohort studies of the entire New Zealand
      population were conducted, using probabilistically-linked Census and mortality
      data from 1981 to 2011 (68.9 million person years). Absolute (standardized rate
      difference) and relative (standardized rate ratio) inequalities were calculated,
      in 1-74-year-olds, for Maori and Pacific peoples in comparison to European/Other.
      RESULTS: All-cause mortality rates were highest for Maori, followed by Pacific
      peoples then European/Other, and declined in all three ethnic groups over time.
      Pacific peoples experienced the slowest annual percentage fall in mortality
      rates, then Maori, with European/Other having the highest percentage falls -
      resulting in widening relative inequalities. Absolute inequalities, however, for
      both Maori and Pacific males compared to European/Other have been falling since
      1996. But for females, only Maori absolute inequalities (compared with
      European/Other) have been falling. Regarding cause of death, cancer is becoming a
      more important contributor than cardiovascular disease (CVD) to absolute
      inequalities, especially for Maori females. CONCLUSIONS: We found declines in all
      cause mortality rates, over time, for each ethnic group of interest. Ethnic
      mortality inequalities are generally stable or even falling in absolute terms,
      but have increased on a relative scale. The drivers of these inequalities in
      mortality are transitioning over time, away from CVD to cancer and diabetes; such
      transitions are likely in other countries, and warrant further research. To
      address these inequalities, policymakers need to enhance prevention activities
      and health care delivery, but also support wider improvements in educational
      achievement and socioeconomic position for highest need populations.

PMID- 28450813
TI  - Self-reported general health, physical distress, mental distress, and activity
      limitation by US county, 1995-2012.
AB  - BACKGROUND: Metrics based on self-reports of health status have been proposed for
      tracking population health and making comparisons among different populations.
      While these metrics have been used in the US to explore disparities by sex,
      race/ethnicity, and socioeconomic position, less is known about how self-reported
      health varies geographically. This study aimed to describe county-level trends in
      the prevalence of poor self-reported health and to assess the face validity of
      these estimates. METHODS: We applied validated small area estimation methods to
      Behavioral Risk Factor Surveillance System data to estimate annual county-level
      prevalence of four measures of poor self-reported health (low general health,
      frequent physical distress, frequent mental distress, and frequent activity
      limitation) from 1995 and 2012. We compared these measures of poor self-reported
      health to other population health indicators, including risk factor prevalence
      (smoking, physical inactivity, and obesity), chronic condition prevalence
      (hypertension and diabetes), and life expectancy. RESULTS: We found substantial
      geographic disparities in poor self-reported health. Counties in parts of South
      Dakota, eastern Kentucky and western West Virginia, along the Texas-Mexico
      border, along the southern half of the Mississippi river, and in southern Alabama
      generally experienced the highest levels of poor self-reported health. At the
      county level, there was a strong positive correlation among the four measures of
      poor self-reported health and between the prevalence of poor self-reported health
      and the prevalence of risk factors and chronic conditions. There was a strong
      negative correlation between prevalence of poor self-reported health and life
      expectancy. Nonetheless, counties with similar levels of poor self-reported
      health experienced life expectancies that varied by several years. Changes over
      time in life expectancy were only weakly correlated with changes in the
      prevalence of poor self-reported health. CONCLUSIONS: This analysis adds to the
      growing body of literature documenting large geographic disparities in health
      outcomes in the United States. Health metrics based on self-reports of health
      status can and should be used to complement other measures of population health,
      such as life expectancy, to identify high need areas, efficiently allocate
      resources, and monitor geographic disparities.

PMID- 28450814
TI  - Medical Foods.

PMID- 28450816
TI  - Hepatitis C Point-of-Care Screening in Retail Pharmacies in the United States.
AB  - Background and Aims: Approximately half of adults with hepatitis C in the United
      States do not know their infection status, and the majority of persons who know
      they are positive for hepatitis C virus (HCV) antibodies fail to receive care. We
      conducted a screening program in retail pharmacies and calculated the percentages
      of anti-HCV-positive individuals and how many subsequently entered a pathway to
      care. Methods: At 45 Walgreens retail pharmacies in 9 US cities, direct store
      advertising was used to recruit individuals for HCV antibody testing.
      Participants were at least 18 years old with at least 1 HCV risk factor, such as
      being born between 1945 and 1965. One day per week at each site, a phlebotomist
      obtained consent from interested participants and performed the testing. Within 3
      business days, an HCV management specialist contacted anti-HCV-positive
      individuals and provided test results and a pathway for obtaining HCV RNA
      testing. During the following 21 to 28 days, the same HCV management specialist
      telephoned individuals to determine whether they underwent an HCV RNA test.
      Results: Between September 2015 and February 2016, 1298 individuals consented.
      Two patients withdrew consent after testing. In all, 8% (103/1296) were HCV
      antibody-positive; of them, 91 (88%) were contacted by an HCV management
      specialist. During the 21- to 28-day follow-up, 56 individuals (62%; 56/91) were
      reached by an HCV management specialist, and 29 (52%; 29/56) confirmed that an
      HCV RNA test was ordered. Conclusions: These results provide evidence in support
      of point-of-care HCV screening in retail pharmacies for at-risk individuals in
      the United States.

PMID- 28450815
TI  - Evidence-Based Guide on Capsule Endoscopy for Small Bowel Bleeding.
AB  - Capsule endoscopy is the diagnostic test of choice for the evaluation of overt
      and occult small bowel bleeding. Its yield is higher in patients presenting with
      overt bleeding. The yield is also improved if the capsule is performed soon after
      the presentation of bleeding. Capsule endoscopy has a complementary role with
      cross-sectional imaging to triage patients for appropriate management, including
      deep enteroscopy, surgery, or, if negative, conservative management. Although
      capsule endoscopy is useful to detect vascular and inflammatory lesions, it
      appears to have a significant miss rate for solitary small bowel lesions,
      including tumors. The main adverse event is capsule retention in patients with
      underlying small bowel obstruction.

PMID- 28450818
TI  - The Role of Regorafenib in Hepatocellular Carcinoma.

PMID- 28450817
TI  - The Emerging Therapeutic Role of Medical Foods for Gastrointestinal Disorders.
AB  - In addition to drugs approved by the US Food and Drug Administration (FDA) that
      treat, cure, or mitigate disease, medical foods are a tool to help manage chronic
      conditions and diseases. A medical food, according to the FDA, is a food that is
      developed to be eaten or administered enterally under the guidance of a physician
      and that is meant for the specific dietary management of a condition or disease
      for which distinctive nutritional requirements, based upon known scientific
      principles, are established by medical evaluation. A variety of medical foods
      exist to help manage a wide range of medical conditions, from Alzheimer disease
      to HIV-associated enteropathy. EnteraGam contains serum-derived bovine
      immunoglobulin/protein isolate, which has been studied extensively in diarrhea
      predominant irritable bowel syndrome, inflammatory bowel disease (IBD), and HIV
      associated enteropathy. VSL#3 is a probiotic that is used in pouchitis for
      patients with ulcerative colitis as well as irritable bowel syndrome. Modulen IBD
      is a whole-protein, sole-nutrition formulation used to manage the active phase of
      Crohn's disease. Vivonex is an elemental diet that is used in a variety of
      diseases associated with severe gastrointestinal dysfunction. Medical foods are
      safe and must have proven efficacy in helping to manage a variety of
      gastrointestinal conditions and diseases. These therapies represent tools that
      can be used prior or in addition to traditional medical therapies. This article
      discusses the history and development of medical foods under the FDA and
      concentrates specifically on medical foods used to help manage diseases of the
      gastrointestinal tract.

PMID- 28450819
TI  - Reversal of Immunogenicity in Inflammatory Bowel Disease.

PMID- 28450820
TI  - Surgical Options for the Treatment of Gastroesophageal Reflux Disease.

PMID- 28450821
TI  - Key Questions in Gastrointestinal Endoscopy to Guide Future Research.

PMID- 28450822
TI  - Controversies in Liver Transplantation.

PMID- 28450823
TI  - Proteomic profiling of human intraschisis cavity fluid.
AB  - BACKGROUND: X-linked retinoschisis (XLRS) is a vitreoretinal degenerative
      disorder causing vision deterioration, due to structural defects in retina. The
      hallmark of this disease includes radial streaks arising from the fovea and
      splitting of inner retinal layers (schisis). Although these retinal changes are
      attributed to mutations in the retinoschisin gene, schisis is also observed in
      patients who do not carry mutations. In addition, the origin of intraschisis
      fluid, the triggering point of schisis formation and its progression are largely
      unknown still. So far, there is no report on the complete proteomic analysis of
      this fluid. Schisis fluid proteome could reflect biochemical changes in the
      disease condition, helping in better understanding and management of
      retinoschisis. Therefore it was of interest to investigate the intraschisis fluid
      proteome using high-resolution mass spectrometry. METHODS: Two male XLRS patients
      (aged 4 and 40 years) underwent clinical and genetic evaluation followed by
      surgical extraction of intraschisis fluids. The two fluid samples were resolved
      on a SDS-PAGE and the processed peptides were analyzed by Q-Exactive plus hybrid
      quadrupole-Orbitrap mass spectrometry. Functional annotation of the identified
      proteins was performed using Ingenuity pathway analysis software. RESULTS: Mass
      spectrometry analysis detected 770 nonredundant proteins in the intraschisis
      fluid. Retinol dehydrogenase 14 was found to be abundant in the schisis fluid.
      Gene ontology based analysis indicated that 19% of the intraschisis fluid
      proteins were localized to the extracellular matrix and 15% of the proteins were
      involved in signal transduction. Functional annotation identified three primary
      canonical pathways to be associated with the schisis fluid proteome viz., LXR/RXR
      activation, complement system and acute phase response signalling, which are
      involved in immune and inflammatory responses. Collectively, our results show
      that intraschisis fluid comprises specific inflammatory proteins which highly
      reflect the disease environment. CONCLUSION: Based on our study, it is suggested
      that inflammation might play a key role in the pathogenesis of XLRS. To our
      knowledge, this is the first report describing the complete proteome of
      intraschisis fluid, which could serve as a template for future research and
      facilitate the development of therapeutic modalities for XLRS.

PMID- 28450824
TI  - Identification of novel biomarker and therapeutic target candidates for acute
      intracerebral hemorrhage by quantitative plasma proteomics.
AB  - BACKGROUND: The systematic mechanisms of acute intracerebral hemorrhage are still
      unknown and unverified, although many recent researches have indicated the
      secondary insults. This study was aimed to disclose the pathological mechanism
      and identify novel biomarker and therapeutic target candidates by plasma
      proteome. METHODS: Patients with AICH (n = 8) who demographically matched healthy
      controls (n = 4) were prospectively enrolled, and their plasma samples were
      obtained. The TMT-LC-MS/MS-based proteomics approach was used to quantify the
      differential proteome across plasma samples, and the results were analyzed by
      Ingenuity Pathway Analysis to explore canonical pathways and the relationship
      involved in the uploaded data. RESULTS: Compared with healthy controls, there
      were 31 differentially expressed proteins in the ICH group (P < 0.05), of which
      21 proteins increased while 10 proteins decreased in abundance. These proteins
      are involved in 21 canonical pathways. One network with high confidence level was
      selected by the function network analysis, in which 23 proteins, P38MAPK and
      NFkappaB signaling pathways participated. Upstream regulator analysis found two
      regulators, IL6 and TNF, with an activation z-score. Seven biomarker candidates:
      APCS, FGB, LBP, MGMT, IGFBP2, LYZ, and APOA4 were found. Six candidate proteins
      were selected to assess the validity of the results by subsequent Western
      blotting analysis. CONCLUSION: Our analysis provided several intriguing pathways
      involved in ICH, like LXR/RXR activation, acute phase response signaling, and
      production of NO and ROS in macrophages pathways. The three upstream regulators:
      IL-6, TNF, LPS, and seven biomarker candidates: APCS, APOA4, FGB, IGFBP2, LBP,
      LYZ, and MGMT were uncovered. LPS, APOA4, IGFBP2, LBP, LYZ, and MGMT are novel
      potential biomarkers in ICH development. The identified proteins and pathways
      provide new perspectives to the potential pathological mechanism and therapeutic
      targets underlying ICH.

PMID- 28450825
TI  - Regioselective Enzymatic Carboxylation of Bioactive (Poly)phenols.
AB  - In order to extend the applicability of the regioselective enzymatic
      carboxylation of phenols, the substrate scope of o-benzoic acid (de)carboxylases
      has been investigated towards complex molecules with an emphasis on flavouring
      agents and polyphenols possessing antioxidant properties. o-Hydroxycarboxylic
      acid products were obtained with perfect regioselectivity, in moderate to
      excellent yields. The applicability of this method was proven by the
      regioselective bio-carboxylation of resveratrol on a preparative scale with 95%
      yield.

PMID- 28450826
TI  - Scene Configuration and Object Reliability Affect the Use of Allocentric
      Information for Memory-Guided Reaching.
AB  - Previous research has shown that egocentric and allocentric information is used
      for coding target locations for memory-guided reaching movements. Especially,
      task-relevance determines the use of objects as allocentric cues. Here, we
      investigated the influence of scene configuration and object reliability as a
      function of task-relevance on allocentric coding for memory-guided reaching. For
      that purpose, we presented participants images of a naturalistic breakfast scene
      with five objects on a table and six objects in the background. Six of these
      objects served as potential reach-targets (= task-relevant objects). Participants
      explored the scene and after a short delay, a test scene appeared with one of the
      task-relevant objects missing, indicating the location of the reach target. After
      the test scene vanished, participants performed a memory-guided reaching movement
      toward the target location. Besides removing one object from the test scene, we
      also shifted the remaining task-relevant and/or task-irrelevant objects left- or
      rightwards either coherently in the same direction or incoherently in opposite
      directions. By varying object coherence, we manipulated the reliability of task
      relevant and task-irrelevant objects in the scene. In order to examine the
      influence of scene configuration (distributed vs. grouped arrangement of task
      relevant objects) on allocentric coding, we compared the present data with our
      previously published data set (Klinghammer et al., 2015). We found that reaching
      errors systematically deviated in the direction of object shifts, but only when
      the objects were task-relevant and their reliability was high. However, this
      effect was substantially reduced when task-relevant objects were distributed
      across the scene leading to a larger target-cue distance compared to a grouped
      configuration. No deviations of reach endpoints were observed in conditions with
      shifts of only task-irrelevant objects or with low object reliability
      irrespective of task-relevancy. Moreover, when solely task-relevant objects were
      shifted incoherently, the variability of reaching endpoints increased compared to
      coherent shifts of task-relevant objects. Our results suggest that the use of
      allocentric information for coding targets for memory-guided reaching depends on
      the scene configuration, in particular the average distance of the reach target
      to task-relevant objects, and the reliability of task-relevant allocentric
      information.

PMID- 28450827
TI  - Understanding the Influences of EEG Reference: A Large-Scale Brain Network
      Perspective.
AB  - The influence of reference is a critical issue for the electroencephalography
      (EEG) and event-related potentials (ERPs) studies. However, previous
      investigations concentrated less on the location of source at a systematic
      neuroscience level. Our goal was to examine the EEG signal associated with the
      locations from a common network parcellation of the human brain function,
      offering a system perspective of the influence of EEG reference. In our
      simulation, vertices uniformly distributed in eight large-scale brain networks
      were adopted to generate the scalp EEG. The brain networks contain the visual,
      somatomotor, dorsal attention, ventral attention, limbic, frontoparietal, default
      networks, and the deep brain structure. The distributions of the most sensitive
      and neutral electrodes were calculated for each network based on the lead-field
      matrix. While the most sensitive electrode had a network-specific symmetric
      pattern, the electrodes in scalp surface had approximately equal chance to be the
      most neutral electrode. Simulated data were referenced at the FCz, the Oz, the
      mean mastoids (MM), the average (AVE), and the infinity reference obtained by the
      reference electrode standardization technique (REST). Intriguingly, the relative
      error followed the pattern REST<AVE<MM<(FCz, Oz), regardless of the number of
      electrodes and signal-to-noise ratios. Our findings suggested that REST was a
      potentially preferable reference for all large-scale networks and AVE virtually
      performed as REST under several conditions. As EEG and ERPs experiments within
      the same behavioral domain always have activations in some specific brain
      networks, the comparisons revealed here may provide a valuable recommendation for
      reference selection in clinical and basic researches.

PMID- 28450828
TI  - Spine Enlargement of Pyramidal Tract-Type Neurons in the Motor Cortex of a Rat
      Model of Levodopa-Induced Dyskinesia.
AB  - Growing evidence suggests that abnormal synaptic plasticity of cortical neurons
      underlies levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). Spine
      morphology reflects synaptic plasticity resulting from glutamatergic
      transmission. We previously reported that enlargement of the dendritic spines of
      intratelencephalic-type (IT) neurons in the primary motor cortex (M1) is linked
      to the development of LID. However, the relevance of another M1 neuron type,
      pyramidal-tract (PT) neurons, to LID remains unknown. We examined the
      morphological changes of the dendritic spines of M1 PT neurons in a rat model of
      LID. We quantified the density and size of these spines in 6-hydroxydopamine
      lesioned rats (a model of PD), 6-hydroxydopamine-lesioned rats chronically
      treated with levodopa (a model of LID), and control rats chronically treated with
      levodopa. Dopaminergic denervation alone had no effect on spine density and head
      area. However, the LID model showed significant increases in the density and
      spine head area and the development of dyskinetic movements. In contrast,
      levodopa treatment of normal rats increased spine density alone. Although,
      chronic levodopa treatment increases PT neuron spine density, with or without
      dopaminergic denervation, enlargement of PT neuron spines appears to be a
      specific feature of LID. This finding suggests that PT neurons become
      hyperexcited in the LID model, in parallel with the enlargement of spines. Thus,
      spine enlargement, and the resultant hyperexcitability of PT pyramidal neurons,
      in the M1 cortex might contribute to abnormal cortical neuronal plasticity in
      LID.

PMID- 28450829
TI  - Musical Sophistication and the Effect of Complexity on Auditory Discrimination in
      Finnish Speakers.
AB  - Musical experiences and native language are both known to affect auditory
      processing. The present work aims to disentangle the influences of native
      language phonology and musicality on behavioral and subcortical sound feature
      processing in a population of musically diverse Finnish speakers as well as to
      investigate the specificity of enhancement from musical training. Finnish
      speakers are highly sensitive to duration cues since in Finnish, vowel and
      consonant duration determine word meaning. Using a correlational approach with a
      set of behavioral sound feature discrimination tasks, brainstem recordings, and a
      musical sophistication questionnaire, we find no evidence for an association
      between musical sophistication and more precise duration processing in Finnish
      speakers either in the auditory brainstem response or in behavioral tasks, but
      they do show an enhanced pitch discrimination compared to Finnish speakers with
      less musical experience and show greater duration modulation in a complex task.
      These results are consistent with a ceiling effect set for certain sound features
      which corresponds to the phonology of the native language, leaving an opportunity
      for music experience-based enhancement of sound features not explicitly encoded
      in the language (such as pitch, which is not explicitly encoded in Finnish).
      Finally, the pattern of duration modulation in more musically sophisticated
      Finnish speakers suggests integrated feature processing for greater efficiency in
      a real world musical situation. These results have implications for research into
      the specificity of plasticity in the auditory system as well as to the effects of
      interaction of specific language features with musical experiences.

PMID- 28450830
TI  - Spiral Ganglion Neuron Projection Development to the Hindbrain in Mice Lacking
      Peripheral and/or Central Target Differentiation.
AB  - We investigate the importance of the degree of peripheral or central target
      differentiation for mouse auditory afferent navigation to the organ of Corti and
      auditory nuclei in three different mouse models: first, a mouse in which the
      differentiation of hair cells, but not central auditory nuclei neurons is
      compromised (Atoh1-cre; Atoh1f/f ); second, a mouse in which hair cell defects
      are combined with a delayed defect in central auditory nuclei neurons (Pax2-cre;
      Atoh1f/f ), and third, a mouse in which both hair cells and central auditory
      nuclei are absent (Atoh1-/-). Our results show that neither differentiated
      peripheral nor the central target cells of inner ear afferents are needed (hair
      cells, cochlear nucleus neurons) for segregation of vestibular and cochlear
      afferents within the hindbrain and some degree of base to apex segregation of
      cochlear afferents. These data suggest that inner ear spiral ganglion neuron
      processes may predominantly rely on temporally and spatially distinct molecular
      cues in the region of the targets rather than interaction with differentiated
      target cells for a crude topological organization. These developmental data imply
      that auditory neuron navigation properties may have evolved before auditory
      nuclei.

PMID- 28450831
TI  - Cycle-Triggered Cortical Stimulation during Slow Wave Sleep Facilitates Learning
      a BMI Task: A Case Report in a Non-Human Primate.
AB  - Slow wave sleep (SWS) has been identified as the sleep stage involved in
      consolidating newly acquired information. A growing body of evidence has shown
      that delta (1-4 Hz) oscillatory activity, the characteristic
      electroencephalographic signature of SWS, is involved in coordinating interaction
      between the hippocampus and the neocortex and is thought to take a role in
      stabilizing memory traces related to a novel task. This case report describes a
      new protocol that uses neuroprosthetics training of a non-human primate to
      evaluate the effects of surface cortical electrical stimulation triggered from
      SWS cycles. The results suggest that stimulation phase-locked to SWS oscillatory
      activity promoted learning of the neuroprosthetic task. This protocol could be
      used to elucidate mechanisms of synaptic plasticity underlying off-line learning
      during sleep and offers new insights into the role of brain oscillations in
      information processing and memory consolidation.

PMID- 28450833
TI  - Optimal Control Based Stiffness Identification of an Ankle-Foot Orthosis Using a
      Predictive Walking Model.
AB  - Predicting the movements, ground reaction forces and neuromuscular activity
      during gait can be a valuable asset to the clinical rehabilitation community,
      both to understand pathology, as well as to plan effective intervention. In this
      work we use an optimal control method to generate predictive simulations of
      pathological gait in the sagittal plane. We construct a patient-specific model
      corresponding to a 7-year old child with gait abnormalities and identify the
      optimal spring characteristics of an ankle-foot orthosis that minimizes muscle
      effort. Our simulations include the computation of foot-ground reaction forces,
      as well as the neuromuscular dynamics using computationally efficient muscle
      torque generators and excitation-activation equations. The optimal control
      problem (OCP) is solved with a direct multiple shooting method. The solution of
      this problem is physically consistent synthetic neural excitation commands,
      muscle activations and whole body motion. Our simulations produced similar
      changes to the gait characteristics as those recorded on the patient. The
      orthosis-equipped model was able to walk faster with more extended knees.
      Notably, our approach can be easily tuned to simulate weakened muscles, produces
      physiologically realistic ground reaction forces and smooth muscle activations
      and torques, and can be implemented on a standard workstation to produce results
      within a few hours. These results are an important contribution toward bridging
      the gap between research methods in computational neuromechanics and day-to-day
      clinical rehabilitation.

PMID- 28450834
TI  - Communication and Inference of Intended Movement Direction during Human-Human
      Physical Interaction.
AB  - Of particular interest to the neuroscience and robotics communities is the
      understanding of how two humans could physically collaborate to perform motor
      tasks such as holding a tool or moving it across locations. When two humans
      physically interact with each other, sensory consequences and motor outcomes are
      not entirely predictable as they also depend on the other agent's actions. The
      sensory mechanisms involved in physical interactions are not well understood. The
      present study was designed (1) to quantify human-human physical interactions
      where one agent ("follower") has to infer the intended or imagined-but not
      executed-direction of motion of another agent ("leader") and (2) to reveal the
      underlying strategies used by the dyad. This study also aimed at verifying the
      extent to which visual feedback (VF) is necessary for communicating intended
      movement direction. We found that the control of leader on the relationship
      between force and motion was a critical factor in conveying his/her intended
      movement direction to the follower regardless of VF of the grasped handle or the
      arms. Interestingly, the dyad's ability to communicate and infer movement
      direction with significant accuracy improved (>83%) after a relatively short
      amount of practice. These results indicate that the relationship between force
      and motion (interpreting as arm impedance modulation) may represent an important
      means for communicating intended movement direction between biological agents, as
      indicated by the modulation of this relationship to intended direction. Ongoing
      work is investigating the application of the present findings to optimize
      communication of high-level movement goals during physical interactions between
      biological and non-biological agents.

PMID- 28450832
TI  - Transcranial Electric Stimulation for Precision Medicine: A Spatiomechanistic
      Framework.
AB  - During recent years, non-invasive brain stimulation, including transcranial
      electrical stimulation (tES) in general, and transcranial direct current
      stimulation (tDCS) in particular, have created new hopes for treatment of
      neurological and psychiatric diseases. Despite promising primary results in some
      brain disorders, a more widespread application of tES is hindered by the unsolved
      question of determining optimum stimulation protocols to receive meaningful
      therapeutic effects. tES has a large parameter space including various montages
      and stimulation parameters. Moreover, inter- and intra-individual differences in
      responding to stimulation protocols have to be taken into account. These factors
      contribute to the complexity of selecting potentially effective protocols for
      each disorder, different clusters of each disorder, and even each single patient.
      Expanding knowledge in different dimensions of basic and clinical neuroscience
      could help researchers and clinicians to select potentially effective protocols
      based on tES modulatory mechanisms for future clinical studies. In this article,
      we propose a heuristic spatiomechanistic framework which contains nine levels to
      address tES effects on brain functions. Three levels refer to the spatial
      resolution (local, small-scale networks and large-scale networks) and three
      levels of tES modulatory effects based on its mechanisms of action
      (neurochemical, neuroelectrical and oscillatory modulations). At the group level,
      this framework could be helpful to enable an informed and systematic exploration
      of various possible protocols for targeting a brain disorder or its neuroscience
      based clusters. Considering recent advances in exploration of neurodiversity at
      the individual level with different brain mapping technologies, the proposed
      framework might also be used in combination with personal data to design
      individualized protocols for tES in the context of precision medicine in the
      future.

PMID- 28450835
TI  - Bioactives in Chinese Proprietary Medicine Modulates 5alpha-Reductase Activity
      and Gene Expression Associated with Androgenetic Alopecia.
AB  - Androgenetic alopecia (AGA) is characterized by a progressive and patterned
      transformation of thick, pigmented terminal scalp hairs into short, hypo
      pigmented vellus-like hairs. The use of Minoxidil and Finasteride to treat AGA
      are often associated with complications in safety and efficacy. However, herbal
      remedies are deemed to have lesser side effects in many societies. This study
      aims to identify potential hair growth properties of individual compounds from a
      Chinese proprietary medicine known as Yangxue Shengfa capsule (YSC), used in
      China for many years for improving AGA. Six marker compounds, including 2,3,5,4'
      tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), Chlorogenic acid, Emodin,
      Ferulic acid, Isoimperatorin, and Paeoniflorin were used for simultaneous HPLC
      quantification and anti-AGA in-vitro screening. Simultaneous quantification of
      these components was performed on 75% (v/v) methanol extracts of YSC, using a
      Welch Ultimate XB-C18 column and gradient elution. Five compounds significantly
      promoted cell proliferation in cultured immortalized human Dermal Papilla Cells
      (DPC). Multiple genes associated with the progression of AGA, including IGF-1,
      DKK-1, and TGF-beta1, were found to be regulated by some of these compounds.
      Interestingly, Ferulic acid and Emodin demonstrated good pharmacological
      properties against AGA, thereby concluding the potential of these bioactives to
      be used in the treatment against AGA.

PMID- 28450836
TI  - Renal Denervation Promotes Atherosclerosis in Hypertensive Apolipoprotein E
      Deficient Mice Infused with Angiotensin II.
AB  - Objective: To determine the effect of renal denervation (RDN) on the severity of
      atherosclerosis and aortic aneurysm in hypertensive mice. Methods: Hypertension,
      atherosclerosis and aortic aneurysm were induced by subcutaneous infusion of
      angiotensin II (1 MUg/kg/min) for 28 days in apolipoprotein E-deficient mice. RDN
      was conducted using combined surgical and local chemical denervation. The
      norepinephrine concentration in the kidney was measured by high-performance
      liquid chromatography. Blood pressure was measured by the tail-cuff method.
      Atherosclerosis was assessed by Sudan IV staining of the aortic arch. The aortic
      diameter was measured by the morphometric method. The mRNA expression of genes
      associated with atherosclerosis and aortic aneurysm were analyzed by quantitative
      PCR. Results: RDN decreased the median norepinephrine content in the kidney by
      93.4% (n = 5-7, P = 0.003) 5 days after the procedure, indicating that the RDN
      procedure was successful. RDN decreased systolic blood pressure in apolipoprotein
      E-deficient mice. Mice that had RDN had more severe aortic arch atherosclerosis
      (median percentage of Sudan IV positive area: 13.2% in control mice, n = 12, and
      25.4% in mice having RDN, n = 12, P = 0.028). The severity of the atherosclerosis
      was negatively correlated with the renal norepinephrine content (spearman r = 
      0.6557, P = 0.005). RDN did not affect the size of aortic aneurysms formed or the
      incidence of aortic rupture in mice receiving angiotensin II. RDN significantly
      increased the aortic mRNA expression of matrix metalloproteinase-2 (MMP-2).
      Conclusion: RDN promoted atherosclerosis in apolipoprotein E-deficient mice
      infused with angiotensin II associated with upregulation of MMP-2. The higher MMP
      2 expression could be the results of the greater amount of atheroma in the RDN
      mice. The findings suggest further research is needed to assess potentially
      deleterious effects of RDN in patients.

PMID- 28450837
TI  - The Higher-Ed Organizational-Scholar Tension: How Scholarship Compatibility and
      the Alignment of Organizational and Faculty Skills, Values and Support Affects
      Scholar's Performance and Well-Being.
AB  - Scholars and institutions alike are concerned with academic productivity.
      Scholars not only further knowledge in their professional fields, they also bring
      visibility and prestige to themselves and their institutions, which in turn
      attracts research grants and more qualified faculty and graduate students. Many
      studies have been done on scholar productivity, and many of them focus on
      individual factors such as gender, marital status, and individual psychological
      characteristics. Also, a few studies are concerned about scholars' well-being. We
      propose a causal model that considers the compatibility of the scholarship
      dimensions valued by scholars and institutions and their academic alignment with
      actual institutional recognition and support. We test our causal model with data
      from a survey of 803 faculty participants. Our findings shed light on how the
      above academic factors affect not just academic productivity but also a scholar's
      well-being. Importantly, we show that academic alignment plays a crucial
      mediating role when predicting productivity and well-being. These results have
      important implications for university administrators who develop, and faculty who
      work under, policies designed to foster professional development and scholarship.

PMID- 28450838
TI  - The Effect of Feedback and Operational Experience on Children's Rule Learning.
AB  - This study aimed to examine the relative effect of feedback and operational
      experience on children's rule learning in a balance scale task, in which 88
      children under the age of 7 years were asked to judge the state of equilibrium
      under four conditions. In the Control condition, children were required to
      observe the scale and predict which side would tilt down or keep balance, without
      feedback on the correctness of their answer. In the Operation (Op) condition,
      children were required to place the weights on the scale just like the
      experimenter did before they made predictions. In the Feedback (Fe) condition,
      feedback was provided for each prediction, but children were not allowed to
      operate the scale. In the Op-Fe condition, children could operate the scale and
      they were provided feedback for each prediction. The results showed that, (1)
      children in Control condition merely adopted the lowest level of rule, the Weight
      Rule; (2) when they were either given feedback or the opportunity to operate the
      scale, they used a higher level rule, such as the Distance Rule, more frequently;
      and feedback was more effective than the operational experience was in promoting
      rule learning; (3) when they were allowed to operate the scale, and were
      simultaneously provided feedback, rule learning increased markedly, suggesting
      that feedback-based operation is the most efficient method for facilitating
      children's rule learning.

PMID- 28450839
TI  - Investigating the Prospective Sense of Agency: Effects of Processing Fluency,
      Stimulus Ambiguity, and Response Conflict.
AB  - How do we know how much control we have over our environment? The sense of agency
      refers to the feeling that we are in control of our actions, and that, through
      them, we can control our external environment. Thus, agency clearly involves
      matching intentions, actions, and outcomes. The present studies investigated the
      possibility that processes of action selection, i.e., choosing what action to
      make, contribute to the sense of agency. Since selection of action necessarily
      precedes execution of action, such effects must be prospective. In contrast, most
      literature on sense of agency has focussed on the retrospective computation
      whether an outcome fits the action performed or intended. This hypothesis was
      tested in an ecologically rich, dynamic task based on a computer game. Across
      three experiments, we manipulated three different aspects of action selection
      processing: visual processing fluency, categorization ambiguity, and response
      conflict. Additionally, we measured the relative contributions of prospective,
      action selection-based cues, and retrospective, outcome-based cues to the sense
      of agency. Manipulations of action selection were orthogonally combined with
      discrepancy of visual feedback of action. Fluency of action selection had a small
      but reliable effect on the sense of agency. Additionally, as expected, sense of
      agency was strongly reduced when visual feedback was discrepant with the action
      performed. The effects of discrepant feedback were larger than the effects of
      action selection fluency, and sometimes suppressed them. The sense of agency is
      highly sensitive to disruptions of action-outcome relations. However, when motor
      control is successful, and action-outcome relations are as predicted, fluency or
      dysfluency of action selection provides an important prospective cue to the sense
      of agency.

PMID- 28450840
TI  - More Than the Win: The Relation between Appetitive Competition Motivation,
      Socialization, and Gender Role Orientation in Women's Football.
AB  - The ability to produce peak performance plays a decisive role in the success of
      athletes in competitive contest situations. Levels of appetitive competition
      motivation (ACM), i.e., the desire to defeat an opponent independent of secondary
      reinforcing factors, were assessed in professional female football/soccer players
      in the premier and regional leagues, using club level as the measurement of sport
      success. Furthermore, the influence of social environments predominantly
      encouraging masculine and competitive play behavior and the players' perceptions
      of their own gender role orientations were investigated. Ninety female football
      players from the German premier league (44) and regional leagues (46)
      participated (age: M = 24, SD = 5 years). Questionnaires ascertaining ACM and
      self-perceptions of gender via gender-role stereotypes, childhood play behavior
      and style of upbringing were utilized. Premier league athletes showed a
      significantly greater inclination toward direct sporting confrontations. Almost
      50% of the variance in ACM between the premier and regional league athletes was
      determined by modern upbringing style and the development of gender roles not
      corresponding to classic female gender stereotypes. The results emphasize the
      significance of ACM as an important facet in competitive sports and illustrate
      the influence of socialization on athletic performance.

PMID- 28450841
TI  - Gaze Behavior Consistency among Older and Younger Adults When Looking at
      Emotional Faces.
AB  - The identification of non-verbal emotional signals, and especially of facial
      expressions, is essential for successful social communication among humans.
      Previous research has reported an age-related decline in facial emotion
      identification, and argued for socio-emotional or aging-brain model explanations.
      However, more perceptual differences in the gaze strategies that accompany facial
      emotional processing with advancing age have been under-explored yet. In this
      study, 22 young (22.2 years) and 22 older (70.4 years) adults were instructed to
      look at basic facial expressions while their gaze movements were recorded by an
      eye-tracker. Participants were then asked to identify each emotion, and the
      unbiased hit rate was applied as performance measure. Gaze data were first
      analyzed using traditional measures of fixations over two preferential regions of
      the face (upper and lower areas) for each emotion. Then, to better capture core
      gaze changes with advancing age, spatio-temporal gaze behaviors were deeper
      examined using data-driven analysis (dimension reduction, clustering). Results
      first confirmed that older adults performed worse than younger adults at
      identifying facial expressions, except for "joy" and "disgust," and this was
      accompanied by a gaze preference toward the lower-face. Interestingly, this
      phenomenon was maintained during the whole time course of stimulus presentation.
      More importantly, trials corresponding to older adults were more tightly
      clustered, suggesting that the gaze behavior patterns of older adults are more
      consistent than those of younger adults. This study demonstrates that, confronted
      to emotional faces, younger and older adults do not prioritize or ignore the same
      facial areas. Older adults mainly adopted a focused-gaze strategy, consisting in
      focusing only on the lower part of the face throughout the whole stimuli display
      time. This consistency may constitute a robust and distinctive "social signature"
      of emotional identification in aging. Younger adults, however, were more
      dispersed in terms of gaze behavior and used a more exploratory-gaze strategy,
      consisting in repeatedly visiting both facial areas.

PMID- 28450842
TI  - Facilitatory Effects of Multi-Word Units in Lexical Processing and Word Learning:
      A Computational Investigation.
AB  - Previous studies have suggested that children and adults form cognitive
      representations of co-occurring word sequences. We propose (1) that the formation
      of such multi-word unit (MWU) representations precedes and facilitates the
      formation of single-word representations in children and thus benefits word
      learning, and (2) that MWU representations facilitate adult word recognition and
      thus benefit lexical processing. Using a modified version of an existing
      computational model (McCauley and Christiansen, 2014), we extract MWUs from a
      corpus of child-directed speech (CDS) and a corpus of conversations among adults.
      We then correlate the number of MWUs within which each word appears with (1) age
      of first production and (2) adult reaction times on a word recognition task. In
      doing so, we take care to control for the effect of word frequency, as frequent
      words will naturally tend to occur in many MWUs. We also compare results to a
      baseline model which randomly groups words into sequences-and find that MWUs have
      a unique facilitatory effect on both response variables, suggesting that they
      benefit word learning in children and word recognition in adults. The effect is
      strongest on age of first production, implying that MWUs are comparatively more
      important for word learning than for adult lexical processing. We discuss
      possible underlying mechanisms and formulate testable predictions.

PMID- 28450843
TI  - Exploring Tactile Perceptual Dimensions Using Materials Associated with Sensory
      Vocabulary.
AB  - Considering tactile sensation when designing products is important because the
      decision to purchase often depends on how products feel. Numerous psychophysical
      studies have attempted to identify important factors that describe tactile
      perceptions. However, the numbers and types of major tactile dimensions reported
      in previous studies have varied because of differences in materials used across
      experiments. To obtain a more complete picture of perceptual space with regard to
      touch, our study focuses on using vocabulary that expresses tactile sensations as
      a guiding principle for collecting material samples because these types of words
      are expected to cover all the basic categories within tactile perceptual space.
      We collected 120 materials based on a variety of Japanese sound-symbolic words
      for tactile sensations, and used the materials to examine tactile perceptual
      dimensions and their associations with affective evaluations. Analysis revealed
      six major dimensions: "Affective evaluation and Friction," "Compliance,"
      "Surface," "Volume," "Temperature," and "Naturalness." These dimensions include
      four factors that previous studies have regarded as fundamental, as well as two
      new factors: "Volume" and "Naturalness." Additionally, we showed that "Affective
      evaluation" is more closely related to the "Friction" component (slipperiness and
      dryness) than to other tactile perceptual features. Our study demonstrates that
      using vocabulary could be an effective method for selecting material samples to
      explore tactile perceptual space.

PMID- 28450844
TI  - Stimulus Control Over Action for Food in Obese versus Healthy-weight Individuals.
AB  - In the current study we examined an associative learning mechanism by which food
      cues (signaling low- versus high-calorie food) can bias instrumental responses
      directed toward those foods. To investigate the clinical relevance of this
      mechanism, we used a computerized Pavlovian-to-instrumental transfer task and
      compared performance of 19 severely obese individuals to that of 19 healthy
      weight controls matched for age, education and gender. During the response
      priming test we exposed participants to both food pictures and to Pavlovian cues
      predictive of those food pictures, and examined their biasing effect on
      instrumental choice. As expected, obese participants showed higher priming rates
      for palatable, high-calorie foods (potato chips and chocolate) relative to low
      calorie foods (lettuce and courgette) whereas healthy-weight individuals did not
      show a difference between priming rates for these two food types. We also
      included various measures of impulsivity as well as a slips-of-action task
      designed to investigate the balance between goal-directed and habitual behavioral
      control in these two groups. We did not find any evidence of increased
      impulsivity or reliance on a habitual strategy during the slips-of-action task,
      in obese participants. General Scientific Summary: Our environment is full of
      cues signaling the availability of tasty, but often unhealthy, foods. This study
      suggests that severely obese individuals are particularly sensitive to high
      calorie food cues whereas low-calorie food cues have little effect on their
      behavior.

PMID- 28450845
TI  - Using Exponential Random Graph Models to Analyze the Character of Peer
      Relationship Networks and Their Effects on the Subjective Well-being of
      Adolescents.
AB  - The influences of peer relationships on adolescent subjective well-being were
      investigated within the framework of social network analysis, using exponential
      random graph models as a methodological tool. The participants in the study were
      1,279 students (678 boys and 601 girls) from nine junior middle schools in
      Shenzhen, China. The initial stage of the research used a peer nomination
      questionnaire and a subjective well-being scale (used in previous studies) to
      collect data on the peer relationship networks and the subjective well-being of
      the students. Exponential random graph models were then used to explore the
      relationships between students with the aim of clarifying the character of the
      peer relationship networks and the influence of peer relationships on subjective
      well being. The results showed that all the adolescent peer relationship networks
      in our investigation had positive reciprocal effects, positive transitivity
      effects and negative expansiveness effects. However, none of the relationship
      networks had obvious receiver effects or leaders. The adolescents in partial peer
      relationship networks presented similar levels of subjective well-being on three
      dimensions (satisfaction with life, positive affects and negative affects) though
      not all network friends presented these similarities. The study shows that peer
      networks can affect an individual's subjective well-being. However, whether
      similarities among adolescents are the result of social influences or social
      choices needs further exploration, including longitudinal studies that
      investigate the potential processes of subjective well-being similarities among
      adolescents.

PMID- 28450846
TI  - Perceptually Salient Regions of the Modulation Power Spectrum for Musical
      Instrument Identification.
AB  - The ability of a listener to recognize sound sources, and in particular musical
      instruments from the sounds they produce, raises the question of determining the
      acoustical information used to achieve such a task. It is now well known that the
      shapes of the temporal and spectral envelopes are crucial to the recognition of a
      musical instrument. More recently, Modulation Power Spectra (MPS) have been shown
      to be a representation that potentially explains the perception of musical
      instrument sounds. Nevertheless, the question of which specific regions of this
      representation characterize a musical instrument is still open. An identification
      task was applied to two subsets of musical instruments: tuba, trombone, cello,
      saxophone, and clarinet on the one hand, and marimba, vibraphone, guitar, harp,
      and viola pizzicato on the other. The sounds were processed with filtered
      spectrotemporal modulations with 2D Gaussian windows. The most relevant regions
      of this representation for instrument identification were determined for each
      instrument and reveal the regions essential for their identification. The method
      used here is based on a "molecular approach," the so-called bubbles method.
      Globally, the instruments were correctly identified and the lower values of
      spectrotemporal modulations are the most important regions of the MPS for
      recognizing instruments. Interestingly, instruments that were confused with each
      other led to non-overlapping regions and were confused when they were filtered in
      the most salient region of the other instrument. These results suggest that
      musical instrument timbres are characterized by specific spectrotemporal
      modulations, information which could contribute to music information retrieval
      tasks such as automatic source recognition.

PMID- 28450847
TI  - The Role of Cognition, Personality, and Trust in Fraud Victimization in Older
      Adults.
AB  - Older adults are more at risk to become a victim of consumer fraud than any other
      type of crime (Carcach et al., 2001) but the research on the psychological
      profiles of senior fraud victims is lacking. To bridge this significant gap, we
      surveyed 151 (120 female, 111 Caucasian) community-dwelling older adults in
      Southern Ontario between 60 and 90 years of age about their experiences with
      fraud. Participants had not been diagnosed with cognitive impairment or a
      neurological disorder by their doctor and looked after their own finances. We
      assessed their self-reported cognitive abilities using the MASQ, personality on
      the 60-item HEXACO Personality Inventory, and trust tendencies using a scale from
      the World Values Survey. There were no demographic differences between victims
      and non-victims. We found that victims exhibit lower levels of cognitive ability,
      lower honesty-humility, and lower conscientiousness than non-victims. Victims and
      non-victims did not differ in reported levels of interpersonal trust. Subsequent
      regression analyses showed that cognition is an important component in
      victimization over and above other social factors. The present findings suggest
      that fraud prevention programs should focus on improving adults' overall
      cognitive functioning. Further investigation is needed to understand how age
      related cognitive changes affect vulnerability to fraud and which cognitive
      processes are most important for preventing fraud victimization.

PMID- 28450848
TI  - Processing Distracting Non-face Emotional Images: No Evidence of an Age-Related
      Positivity Effect.
AB  - Cognitive aging may be accompanied by increased prioritization of social and
      emotional goals that enhance positive experiences and emotional states. The
      socioemotional selectivity theory suggests this may be achieved by giving
      preference to positive information and avoiding or suppressing negative
      information. Although there is some evidence of a positivity bias in controlled
      attention tasks, it remains unclear whether a positivity bias extends to the
      processing of affective stimuli presented outside focused attention. In two
      experiments, we investigated age-related differences in the effects of to-be
      ignored non-face affective images on target processing. In Experiment 1, 27 older
      (64-90 years) and 25 young adults (19-29 years) made speeded valence judgments
      about centrally presented positive or negative target images taken from the
      International Affective Picture System. To-be-ignored distractor images were
      presented above and below the target image and were either positive, negative, or
      neutral in valence. The distractors were considered task relevant because they
      shared emotional characteristics with the target stimuli. Both older and young
      adults responded slower to targets when distractor valence was incongruent with
      target valence relative to when distractors were neutral. Older adults responded
      faster to positive than to negative targets but did not show increased
      interference effects from positive distractors. In Experiment 2, affective
      distractors were task irrelevant as the target was a three-digit array and did
      not share emotional characteristics with the distractors. Twenty-six older (63-84
      years) and 30 young adults (18-30 years) gave speeded responses on a digit
      disparity task while ignoring the affective distractors positioned in the
      periphery. Task performance in either age group was not influenced by the task
      irrelevant affective images. In keeping with the socioemotional selectivity
      theory, these findings suggest that older adults preferentially process task
      relevant positive non-face images but only when presented within the main focus
      of attention.

PMID- 28450849
TI  - Striatal and Hippocampal Atrophy in Idiopathic Parkinson's Disease Patients
      without Dementia: A Morphometric Analysis.
AB  - BACKGROUND: Analyses of subcortical gray structure volumes in non-demented
      idiopathic Parkinson's disease (PD) often, but not always, show volume loss of
      the putamen, caudate nucleus, nucleus accumbens, and hippocampus. There is
      building evidence that structure morphometry might be more sensitive to disease
      related processes than volume. OBJECTIVE: To assess morphometric differences of
      subcortical structures (putamen, caudate nucleus, thalamus, globus pallidus,
      nucleus accumbens, and amygdala) as well as the hippocampus in non-demented
      individuals with PD relative to age and education matched non-PD peers. METHODS:
      Prospective recruitment of idiopathic no-dementia PD and non-PD peers as part of
      a federally funded investigation. T1-weighted isovoxel metrics acquired via 3-T
      Siemens Verio for all individuals [PD n = 72 (left side onset n = 27, right side
      onset n = 45); non-PD n = 48]. FIRST (FMRIB Software Library) applications
      provided volumetric and vertex analyses on group differences for structure size
      and morphometry. RESULTS: Group volume differences were observed only for putamen
      and hippocampi (PD < non-PD) with hippocampal volume significantly associating
      with disease duration. Group shape differences were observed for bilateral
      putamen, caudate nucleus, and hippocampus with greater striatal atrophy
      contralateral to side of motor symptom onset. Hippocampal shape differences
      disappeared when removing the effects of volume. CONCLUSION: The putamen was the
      primary structure to show both volume and shape differences in PD, indicating
      that the putamen is the predominant site of basal ganglia atrophy in early- to
      mid-stage PD. Side of PD symptom onset associates with contralateral striatal
      atrophy. Left-onset PD might experience more extensive striatal atrophy than
      right-onset PD. Hippocampus morphometric results suggest possible primary atrophy
      of CA3/4 and dentate gyrus.

PMID- 28450850
TI  - Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger.
AB  - Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder
      contraction factor. It was later shown to be member of a peptide family, which
      are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be
      synthetized in small intestinal endocrine I-cells and cerebral neurons. But in
      addition, CCK is expressed in several endocrine glands (pituitary cells, thyroid
      C-cells, pancreatic islets, the adrenals, and the testes); in peripheral nerves;
      in cortical and medullary kidney cells; in cardial myocytes; and in cells of the
      immune system. CCK peptides stimulate pancreatic enzyme secretion and growth,
      gallbladder contraction, and gut motility, satiety and inhibit acid secretion
      from the stomach. Moreover, they are major neurotransmitters in the brain and the
      periphery. CCK peptides also stimulate calcitonin, insulin, and glucagon
      secretion, and they may act as natriuretic peptides in the kidneys. CCK peptides
      are derived from proCCK with a C-terminal bioactive YMGWMDFamide sequence, in
      which the Y-residue is partly O-sulfated. The plasma forms are CCK-58, -33, -22,
      and -8, whereas the small CCK-8 and -5 are potent neurotransmitters. Over the
      last decades, CCK expression has also been encountered in tumors (neuroendocrine
      tumors, cerebral astrocytomas, gliomas, acoustic neuromas, and specific pediatric
      tumors). Recently, a metastastic islet cell tumor was found to cause a specific
      CCKoma syndrome, suggesting that circulating CCK may be a useful tumor marker.

PMID- 28450851
TI  - Regulation of Agouti-Related Protein and Pro-Opiomelanocortin Gene Expression in
      the Avian Arcuate Nucleus.
AB  - The arcuate nucleus is generally conserved across vertebrate taxa in its
      neuroanatomy and neuropeptide expression. Gene expression of agouti-related
      protein (AGRP), neuropeptide Y (NPY), pro-opiomelanocortin (POMC), and cocaine-
      and amphetamine-regulated transcript (CART) has been established in the arcuate
      nucleus of several bird species and co-localization demonstrated for AGRP and
      NPY. The proteins encoded by these genes exert comparable effects on food intake
      in birds after central administration to those seen in other vertebrates, with
      AGRP and NPY being orexigenic and CART and alpha-melanocyte-stimulating hormone
      anorexigenic. We have focused on the measurement of arcuate nucleus AGRP and POMC
      expression in several avian models in relation to the regulation of energy
      balance, incubation, stress, and growth. AGRP mRNA and POMC mRNA are,
      respectively, up- and downregulated after energy deprivation and restriction.
      This suggests that coordinated changes in the activity of AGRP and POMC neurons
      help to drive the homeostatic response to replace depleted energy stores in birds
      as in other vertebrates. While AGRP and POMC expression are generally positively
      and negatively correlated with food intake, respectively, we review here
      situations in some avian models in which AGRP gene expression is dissociated from
      the level of food intake and may have an influence on growth independent of
      changes in appetite. This suggests the possibility that the central melanocortin
      system exerts more pleiotropic functions in birds. While the neuroanatomical
      arrangement of AGRP and POMC neurons and the sensitivity of their activity to
      nutritional state appear generally conserved with other vertebrates, detailed
      knowledge is lacking of the key nutritional feedback signals acting on the avian
      arcuate nucleus and there appear to be significant differences between birds and
      mammals. In particular, recently identified avian leptin genes show differences
      between bird species in their tissue expression patterns and appear less closely
      linked in their expression to nutritional state. It is presently uncertain how
      the regulation of the central melanocortin system in birds is brought about in
      the situation of the apparently reduced importance of leptin and ghrelin compared
      to mammals.

PMID- 28450852
TI  - Pan-Genomic Analysis Permits Differentiation of Virulent and Non-virulent Strains
      of Xanthomonas arboricola That Cohabit Prunus spp. and Elucidate Bacterial
      Virulence Factors.
AB  - Xanthomonas arboricola is a plant-associated bacterial species that causes
      diseases on several plant hosts. One of the most virulent pathovars within this
      species is X. arboricola pv. pruni (Xap), the causal agent of bacterial spot
      disease of stone fruit trees and almond. Recently, a non-virulent Xap-look-a-like
      strain isolated from Prunus was characterized and its genome compared to
      pathogenic strains of Xap, revealing differences in the profile of virulence
      factors, such as the genes related to the type III secretion system (T3SS) and
      type III effectors (T3Es). The existence of this atypical strain arouses several
      questions associated with the abundance, the pathogenicity, and the evolutionary
      context of X. arboricola on Prunus hosts. After an initial characterization of a
      collection of Xanthomonas strains isolated from Prunus bacterial spot outbreaks
      in Spain during the past decade, six Xap-look-a-like strains, that did not
      clustered with the pathogenic strains of Xap according to a multi locus sequence
      analysis, were identified. Pathogenicity of these strains was analyzed and the
      genome sequences of two Xap-look-a-like strains, CITA 14 and CITA 124, non
      virulent to Prunus spp., were obtained and compared to those available genomes of
      X. arboricola associated with this host plant. Differences were found among the
      genomes of the virulent and the Prunus non-virulent strains in several characters
      related to the pathogenesis process. Additionally, a pan-genomic analysis that
      included the available genomes of X. arboricola, revealed that the atypical
      strains associated with Prunus were related to a group of non-virulent or low
      virulent strains isolated from a wide host range. The repertoire of the genes
      related to T3SS and T3Es varied among the strains of this cluster and those
      strains related to the most virulent pathovars of the species, corylina,
      juglandis, and pruni. This variability provides information about the potential
      evolutionary process associated to the acquisition of pathogenicity and host
      specificity in X. arboricola. Finally, based in the genomic differences observed
      between the virulent and the non-virulent strains isolated from Prunus, a
      sensitive and specific real-time PCR protocol was designed to detect and identify
      Xap strains. This method avoids miss-identifications due to atypical strains of
      X. arboricola that can cohabit Prunus.

PMID- 28450853
TI  - Micromanagement of Immune System: Role of miRNAs in Helminthic Infections.
AB  - Helminthic infections fall under neglected tropical diseases, although they
      inflict severe morbidity to human and causes major economic burden on health care
      system in many developing countries. There is increased effort to understand
      their immunopathology in recent days due to their immuno-modulatory capabilities.
      Immune response is primarily controlled at the transcriptional level, however,
      microRNA-mediated RNA interference is emerging as important regulatory machinery
      that works at the translation level. In the past decade, microRNA (miRNA/miR)
      research has advanced with significant momentum. The result is ever increasing
      list of curated sequences from a broad panel of organisms including helminths.
      Several miRNAs had been discovered from trematodes, nematodes and cestodes like
      let-7, miR155, miR-199, miR-134, miR-223, miR-146, and fhe-mir-125a etc., with
      potential role in immune modulation. These miRs had been associated with TGF
      beta, MAPK, Toll-like receptor, PI3K/AKT signaling pathways and insulin growth
      factor regulation. Thus, controlling the immune cells development, survival,
      proliferation and death. Apart from micromanagement of immune system, they also
      express certain unique miRNA also like cis-miR-001, cis-miR-2, cis-miR-6, cis-miR
      10, cis-miR-18, cis-miR-19, trs-mir-0001, fhe-miR-01, fhe-miR-07, fhe-miR-08, egr
      miR-4988, egr-miR-4989 etc. The specific role played by most of these species
      specific unique miRs are yet to be discovered. However, these newly discovered
      miRNAs might serve as novel targets for therapeutic intervention or biomarkers
      for parasitic infections.

PMID- 28450854
TI  - Microbial Disease Spectrum Linked to a Novel IL-12Rbeta1 N-Terminal Signal
      Peptide Stop-Gain Homozygous Mutation with Paradoxical Receptor Cell-Surface
      Expression.
AB  - Patients with Mendelian Susceptibility to Mycobacterial Diseases (MSMD) exhibit
      variable vulnerability to infections by mycobacteria and other intramacrophagic
      bacteria (e.g., Salmonella and Klebsiella) and fungi (e.g., Histoplasma, Candida,
      Paracoccidioides, Coccidioides, and Cryptococcus). The hallmark of MSMD is the
      inherited impaired production of interferon gamma (IFN-gamma) or the lack of
      response to it. Mutations in the interleukin (IL)-12 receptor subunit beta 1
      (IL12RB1) gene accounts for 38% of cases of MSMD. Most IL12RB1 pathogenic allele
      mutations, including ten known stop-gain variants, cause IL-12Rbeta1 complete
      deficiency (immunodeficiency-30, IMD30) by knocking out receptor cell-surface
      expression. IL12RB1 loss-of-function genotypes impair both IL-12 and IL-23
      responses. Here, we assess the health effects of a rare, novel IL12RB1 stop-gain
      homozygous genotype with paradoxical IL-12Rbeta1 cell-surface expression. We
      appraise four MSMD children from three unrelated Brazilian kindreds by clinical
      consultation, medical records, and genetic and immunologic studies. The clinical
      spectrum narrowed down to Bacillus Calmette-Guerin (BCG) vaccine-related
      suppurative adenitis in all patients with one death, and recrudescence in two,
      histoplasmosis, and recurrence in one patient, extraintestinal salmonellosis in
      one child, and cutaneous vasculitis in another. In three patients, we established
      the homozygous Trp7Ter predicted loss-of-function inherited genotype and inferred
      it from the heterozygote parents of the fourth case. The Trp7Ter mutation maps to
      the predicted IL-12Rbeta1 N-terminal signal peptide sequence. BCG- or
      phytohemagglutinin-blasts from the three patients have reduced cell-surface
      expression of IL-12Rbeta1 with impaired production of IFN-gamma and IL-17A.
      Screening of 227 unrelated healthy subjects from the same geographic region
      revealed one heterozygous genotype (allele frequency 0.0022) vs. one in over
      841,883 public genome/exomes. We also show that the carriers bear European
      ancestry-informative alleles and share the extended CACCAGTCCGG IL12RB1 haplotype
      that occurs worldwide with a frequency of 8.4%. We conclude that the novel
      IL12RB1 N-terminal signal peptide stop-gain loss-of-function homozygous genotype
      confers IL-12Rbeta1 deficiency with varying severity and early-onset age through
      diminished cell-surface expression of an impaired IL-12Rbeta1 polypeptide. We
      firmly recommend attending to warning signs of IMD30 in children who are HIV-1
      negative with a history of adverse effects to the BCG vaccine and presenting with
      recurrent Histoplasma spp. and extraintestinal Salmonella spp. infections.

PMID- 28450855
TI  - The Abundance of Endofungal Bacterium Rhizobium radiobacter (syn. Agrobacterium
      tumefaciens) Increases in Its Fungal Host Piriformospora indica during the
      Tripartite Sebacinalean Symbiosis with Higher Plants.
AB  - Rhizobium radiobacter (syn. Agrobacterium tumefaciens, syn. "Agrobacterium
      fabrum") is an endofungal bacterium of the fungal mutualist Piriformospora (syn.
      Serendipita) indica (Basidiomycota), which together form a tripartite
      Sebacinalean symbiosis with a broad range of plants. R. radiobacter strain F4
      (RrF4), isolated from P. indica DSM 11827, induces growth promotion and systemic
      resistance in cereal crops, including barley and wheat, suggesting that R.
      radiobacter contributes to a successful symbiosis. Here, we studied the impact of
      endobacteria on the morphology and the beneficial activity of P. indica during
      interactions with plants. Low numbers of endobacteria were detected in the
      axenically grown P. indica (long term lab-cultured, lcPiri) whereas mycelia
      colonizing the plant root contained increased numbers of bacteria. Higher numbers
      of endobacteria were also found in axenic cultures of P. indica that was freshly
      re-isolated (riPiri) from plant roots, though numbers dropped during repeated
      axenic re-cultivation. Prolonged treatments of P. indica cultures with various
      antibiotics could not completely eliminate the bacterium, though the number of
      detectable endobacteria decreased significantly, resulting in partial-cured P.
      indica (pcPiri). pcPiri showed reduced growth in axenic cultures and poor
      sporulation. Consistent with this, pcPiri also showed reduced plant growth
      promotion and reduced systemic resistance against powdery mildew infection as
      compared with riPiri and lcPiri. These results are consistent with the assumption
      that the endobacterium R. radiobacter improves P. indica's fitness and thus
      contributes to the success of the tripartite Sebacinalean symbiosis.

PMID- 28450856
TI  - Toward a Metagenomic Understanding on the Bacterial Composition and Resistome in
      Hong Kong Banknotes.
AB  - Currency is possibly one of the main media transmitting pathogens and drug
      resistance due to its wide circulation in daily life. In this study, we made a
      comprehensive characterization of the bacterial community present on banknotes
      collected from different geographical regions of Hong Kong (HK) by performing in
      vitro characterization of the bacterial presence and resistome profile, as well
      as metagenomic analysis including microbial diversity, the prevalence of
      potential pathogens, the dissemination potential of antibiotic-resistance genes
      (ARGs), among others. When comparing the bacterial community of HK banknotes with
      other HK environmental samples, including water and marine sediment, we revealed
      that HK banknotes cover nearly 50% of total genera found in all the environmental
      samples, implying that banknotes harbor diverse bacteria originated from a
      variety of environments. Furthermore, the banknotes have higher abundance of
      potential pathogenic species (~5 times more) and ARGs (~5 times more) with higher
      dissemination potential (~48 times more) compared with other environmental
      samples. These findings unveiled the capabilities of this common medium of
      exchange to accommodate various bacteria, and transmit pathogens and antibiotic
      resistance. Furthermore, the observed independence of microbiome profile from the
      city's topological indices led us to formulate a hypothesis that due to their
      high circulation banknotes may harbor a homogenized microbiome.

PMID- 28450857
TI  - The Functional Roles of the Cis-acting Elements in Bamboo mosaic virus RNA
      Genome.
AB  - Bamboo mosaic virus (BaMV), which belongs to the genus Potexvirus in the family
      Alphaflexiviridae, has a single-stranded positive-sense RNA genome that is
      approximately 6400 nucleotides (nts) in length. Positive-sense RNA viruses can
      use genomic RNA as a template for translation and replication after entering a
      suitable host cell. Furthermore, such viral RNA is recognized by capsid protein
      for packaging and by viral movement protein(s) or the movement protein complex
      for cell-to-cell and systemic movement. Hence, viral RNA must contain signals for
      different functions to complete the viral infection cycle. In this review, we
      examine various cis-acting elements in the genome of BaMV. The highly structured
      3' untranslated region (UTR) of the BaMV genomic RNA plays multiple roles in the
      BaMV infection cycle, including targeting chloroplasts for RNA replication,
      providing an initiation site for the synthesis of minus-strand RNA, signaling for
      polyadenylation, and directing viral long-distance movement. The nt at the
      extreme 3' end and the structure of the 3'-terminus of minus-strand RNA are
      involved in the initiation of plus-strand genomic RNA synthesis. Both these
      regions have been mapped and reported to interact with the viral-encoded RNA
      dependent RNA polymerase. Moreover, the sequences upstream of open reading frames
      (ORFs) 2, 3, and 5 are involved in regulating subgenomic RNA synthesis. The cis
      acting elements that were identified in BaMV RNA are discussed and compared with
      those of other potexviruses.

PMID- 28450858
TI  - Fungal Biofilms: Targets for the Development of Novel Strategies in Plant Disease
      Management.
AB  - The global food supply has been facing increasing challenges during the first
      decades of the 21st century. Disease in plants is an important constraint to
      worldwide crop production, accounting for 20-40% of its annual harvest loss.
      Although the use of resistant varieties, good water management and agronomic
      practices are valid management tools in counteracting plant diseases, there are
      still many pathosystems where fungicides are widely used for disease management.
      However, restrictive regulations and increasing concern regarding the risk to
      human health and the environment, along with the incidence of fungicide
      resistance, have discouraged their use and have prompted for a search for new
      efficient, ecologically friendly and sustainable disease management strategies.
      The recent evidence of biofilm formation by fungal phytopathogens provides the
      scientific framework for designing and adapting methods and concepts developed by
      biofilm research that could be integrated in IPM practices. In this perspective
      paper, we provide evidence to support the view that the biofilm lifestyle plays a
      critical role in the pathogenesis of plant diseases. We describe the main factors
      limiting the durability of single-site fungicides, and we assemble the current
      knowledge on pesticide resistance in the specific context of the biofilm
      lifestyle. Finally, we illustrate the potential of antibiofilm compounds at sub
      lethal concentrations for the development of an innovative, eco-sustainable
      strategy to counteract phytopathogenic fungi. Such fungicide-free solutions will
      be instrumental in reducing disease severity, and will permit more prudent use of
      fungicides decreasing thus the selection of resistant forms and safeguarding the
      environment.

PMID- 28450859
TI  - A Comparative Characterization of Different Host-sourced Lactobacillus ruminis
      Strains and Their Adhesive, Inhibitory, and Immunomodulating Functions.
AB  - Lactobacillus ruminis, an autochthonous member of the gastrointestinal microbiota
      of humans and many animals, is a less characterized but interesting species for
      many reasons, including its intestinal prevalence and possible positive roles in
      host-microbe crosstalk. In this study, we isolated a novel L. ruminis strain (GRL
      1172) from porcine feces and analyzed its functional characteristics and niche
      adaptation factors in parallel with those of three other L. ruminis strains (a
      human isolate, ATCC 25644, and two bovine isolates, ATCC 27780 and ATCC 27781).
      All the strains adhered to fibronectin, type I collagen, and human colorectal
      adenocarcinoma cells (HT-29), but poorly to type IV collagen, porcine intestinal
      epithelial cells (IPEC-1), and human colon adenocarcinoma cells (Caco-2). In
      competition assays, all the strains were able to inhibit the adhesion of Yersinia
      enterocolitica and enterotoxigenic Escherichia coli (ETEC, F4+) to fibronectin,
      type I; collagen, IPEC-1, and Caco-2 cells, and the inhibition rates tended to be
      higher than in exclusion assays. The culture supernatants of the tested strains
      inhibited the growth of six selected pathogens to varying extents. The inhibition
      was solely based on the low pH resulting from acid production during growth. All
      four L. ruminis strains supported the barrier function maintenance of Caco-2
      cells, as shown by the modest increase in trans-epithelial electrical resistance
      and the prevention of dextran diffusion during co-incubation. However, the
      strains could not prevent the barrier damage caused by ETEC in the Caco-2 cell
      model. All the tested strains and their culture supernatants were able to provoke
      Toll-like receptor (TLR) 2-mediated NF-kappaB activation and IL-8 production in
      vitro to varying degrees. The induction of TLR5 signaling revealed that flagella
      were expressed by all the tested strains, but to different extents. Flagella and
      pili were observed by electron microscopy on the newly isolated strain GRL 1172.

PMID- 28450860
TI  - Vibrational Spectroscopy for Imaging Single Microbial Cells in Complex Biological
      Samples.
AB  - Vibrational spectroscopy is increasingly used for the rapid and non-destructive
      imaging of environmental and medical samples. Both Raman and Fourier-transform
      infrared (FT-IR) imaging have been applied to obtain detailed information on the
      chemical composition of biological materials, ranging from single microbial cells
      to tissues. Due to its compatibility with methods such as stable isotope labeling
      for the monitoring of cellular activities, vibrational spectroscopy also holds
      considerable power as a tool in microbial ecology. Chemical imaging of
      undisturbed biological systems (such as live cells in their native habitats)
      presents unique challenges due to the physical and chemical complexity of the
      samples, potential for spectral interference, and frequent need for real-time
      measurements. This Mini Review provides a critical synthesis of recent
      applications of Raman and FT-IR spectroscopy for characterizing complex
      biological samples, with a focus on developments in single-cell imaging. We also
      discuss how new spectroscopic methods could be used to overcome current
      limitations of single-cell analyses. Given the inherent complementarity of Raman
      and FT-IR spectroscopic methods, we discuss how combining these approaches could
      enable us to obtain new insights into biological activities either in situ or
      under conditions that simulate selected properties of the natural environment.

PMID- 28450861
TI  - Corrigendum: Assessing the function of STAS domain protein SypA in Vibrio
      fischeri using a comparative analysis.
AB  - [This corrects the article on p. 760 in vol. 6, PMID: 26284045.].

PMID- 28450862
TI  - Differential Response of Mouse Thymic Epithelial Cell Types to Ionizing Radiation
      Induced DNA Damage.
AB  - Thymic epithelial cells (TECs) are the main components of the thymic stroma that
      support and control T-cell development. Preparative regimens using DNA-damaging
      agents, such as total body irradiation and/or chemotherapeutic drugs, that are
      necessary prior to bone marrow transplantation (BMT) have profound deleterious
      effects on the hematopoietic system, including the thymic stroma, which may be
      one of the main causes for the prolonged periods of T-cell deficiency and the
      inefficient T cell reconstitution that are common following BMT. The DNA damage
      response (DDR) is a complex signaling network that allows cells to respond to all
      sorts of genotoxic insults. Hypoxia is known to modulate the DDR and play a role
      affecting the survival capacity of different cell types. In this study, we have
      characterized in detail the DDR of cortical and medullary TEC lines and their
      response to ionizing radiation, as well as the effects of hypoxia on their DDR.
      Although both mTECs and cTECs display relatively high radio-resistance, mTEC
      cells have an increased survival capacity to ionizing radiation (IR)-induced DNA
      damage, and hypoxia specifically decreases the radio-resistance of mTECs by
      upregulating the expression of the pro-apoptotic factor Bim. Analysis of the
      expression of TEC functional factors by primary mouse TECs showed a marked
      decrease of highly important genes for TEC function and confirmed cTECs as the
      most affected cell type by IR. These findings have important implications for
      improving the outcomes of BMT and promoting successful T cell reconstitution.

PMID- 28450863
TI  - The Proteasome Inhibitor Bortezomib Controls Indoleamine 2,3-Dioxygenase 1
      Breakdown and Restores Immune Regulation in Autoimmune Diabetes.
AB  - Bortezomib (BTZ) is a first-in-class proteasome inhibitor approved for the
      therapy of multiple myeloma that also displays unique regulatory activities on
      immune cells. The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan
      metabolizing enzyme exerting potent immunoregulatory effects when expressed in
      dendritic cells (DCs), the most potent antigen-presenting cells capable of
      promoting either immunity or tolerance. We previously demonstrated that, in
      inflammatory conditions, IDO1 is subjected to proteasomal degradation in DCs,
      turning these cells from immunoregulatory to immunostimulatory. In non-obese
      diabetic (NOD) mice, an experimental model of autoimmune diabetes, we also
      identified an IDO1 defect such that the DCs do not develop tolerance toward
      pancreatic islet autoantigens. We found that BTZ rescues IDO1 protein expression
      in vitro in a particular subset of DCs, i.e., plasmacytoid DCs (pDCs) from NOD
      mice. When administered in vivo to prediabetic mice, the drug prevented diabetes
      onset through IDO1- and pDC-dependent mechanisms. Although the drug showed no
      therapeutic activity when administered alone to overtly diabetic mice, its
      combination with otherwise suboptimal dosages of autoimmune-preventive anti-CD3
      antibody resulted in disease reversal in 70% diabetic mice, a therapeutic effect
      similar to that afforded by full-dosage anti-CD3. Thus, our data indicate a
      potential for BTZ in the immunotherapy of autoimmune diabetes and further
      underline the importance of IDO1-mediated immune regulation in such disease.

PMID- 28450864
TI  - Specificity, Privacy, and Degeneracy in the CD4 T Cell Receptor Repertoire
      Following Immunization.
AB  - T cells recognize antigen using a large and diverse set of antigen-specific
      receptors created by a complex process of imprecise somatic cell gene
      rearrangements. In response to antigen-/receptor-binding-specific T cells then
      divide to form memory and effector populations. We apply high-throughput
      sequencing to investigate the global changes in T cell receptor sequences
      following immunization with ovalbumin (OVA) and adjuvant, to understand how
      adaptive immunity achieves specificity. Each immunized mouse contained a
      predominantly private but related set of expanded CDR3beta sequences. We used
      machine learning to identify common patterns which distinguished repertoires from
      mice immunized with adjuvant with and without OVA. The CDR3beta sequences were
      deconstructed into sets of overlapping contiguous amino acid triplets. The
      frequencies of these motifs were used to train the linear programming boosting
      (LPBoost) algorithm LPBoost to classify between TCR repertoires. LPBoost could
      distinguish between the two classes of repertoire with accuracies above 80%,
      using a small subset of triplet sequences present at defined positions along the
      CDR3. The results suggest a model in which such motifs confer degenerate antigen
      specificity in the context of a highly diverse and largely private set of T cell
      receptors.

PMID- 28450865
TI  - Distinct Effects of Dexamethasone on Human Natural Killer Cell Responses
      Dependent on Cytokines.
AB  - Glucocorticoids (GCs) have long been known to be immune suppressive and synthetic
      variants are widely used in the treatment of inflammatory disorders. Here, we
      report that, while suppressing the initial production of interferon-gamma (IFN
      gamma), the synthetic GC dexamethasone (Dex) enhances the proliferation and
      survival of natural killer (NK) cells stimulated with interleukin-2 (IL-2) +
      interleukin-12 (IL-12). Inhibition of mTOR complex 1 by rapamycin revealed the
      immunosuppressive activity of Dex was independent from the effect of enhancing NK
      cell proliferation. In the presence of IL-2 + IL-12, Dex also increased the
      percentage of NK cells that were CD16+ and DNAM1bright, increased the level of
      expression of CD94 or NKG2A, and improved mitochondrial function of NK cells.
      Moreover, NK cells treated with cytokines IL-2 and IL-12 + Dex, followed by a 7
      day rest, displayed an increased IFN-gamma response upon restimulation. Thus,
      there is a dichotomic effect of GCs on NK cell function dependent on the local
      cytokine milieu; the NK cell effector response is initially suppressed, but,
      dependent on the cytokines present, Dex can also augment the proliferation,
      survival, and reactivity of human NK cells in a secondary recall response.

PMID- 28450866
TI  - Impact of Non-Human Leukocyte Antigen-Specific Antibodies in Kidney and Heart
      Transplantation.
AB  - The presence of donor human leukocyte antigen (HLA)-specific antibodies has been
      shown to be associated with graft loss and decreased patient survival, but it is
      not uncommon that donor-specific HLA antibodies are absent in patients with
      biopsy-proven antibody-mediated rejection. In this review, we focus on the latest
      findings on antibodies against non-HLA antigens in kidney and heart
      transplantation. These non-HLA antigens include myosin, vimentin, Kalpha1
      tubulin, collagen, and angiotensin II type 1 receptor. It is suggested that the
      detrimental effects of HLA antibodies and non-HLA antibodies synergize together
      to impact graft outcome. Injury of graft by HLA antibodies can cause the exposure
      of neo-antigens which in turn stimulate the production of antibodies against non
      HLA antigens. On the other hand, the presence of non-HLA antibodies may increase
      the risk for a patient to develop HLA-specific antibodies. These findings
      indicate it is imperative to stratify the patient's immunologic risk by assessing
      both HLA and non-HLA antibodies.

PMID- 28450867
TI  - P2X7 Receptor in Bone Marrow-Derived Cells Aggravates Tuberculosis Caused by
      Hypervirulent Mycobacterium bovis.
AB  - Tuberculosis (TB) remains a serious public health problem despite the great
      scientific advances in the recent decades. We have previously shown that
      aggressive forms of TB caused by hypervirulent strains of Mycobacterium
      tuberculosis and Mycobacterium bovis are attenuated in mice lacking the P2X7
      receptor, an ion channel activated by extracellular ATP. Therefore, P2X7 receptor
      is a potential target for therapeutic intervention. In vitro, hypervirulent
      mycobacteria cause macrophage death by a P2X7-dependent mechanism that
      facilitates bacillus dissemination. However, as P2X7 receptor is expressed in
      both bone marrow (BM)-derived cells and lung structural cells, several cellular
      mechanisms can operate in vivo. To investigate whether the presence of P2X7
      receptor in BM-derived cells contributes to TB severity, we generated chimeric
      mice by adoptive transfer of hematopoietic cells from C57BL/6 or P2X7-/- mice
      into CD45.1 irradiated mice. After infection with hypervirulent mycobacteria
      (MP287/03 strain of M. bovis), P2X7-/->CD45.1 mice recapitulated the TB
      resistance observed in P2X7-/- mice. These chimeric mice showed lower lung
      bacterial load and attenuated pneumonia compared to C57BL/6>CD45.1 mice. Lung
      necrosis and bacterial dissemination to the spleen and liver were also reduced in
      P2X7-/->CD45.1 mice compared to C57BL/6>CD45.1 mice. Furthermore, an immature
      like myeloid cell population showing a Ly6Gint phenotype was observed in the
      lungs of infected C57BL/6 and C57BL/6>CD45.1 mice, whereas P2X7-/- and P2X7-/
      >CD45.1 mice showed a typical neutrophil (Ly6Ghi) population. This study clearly
      demonstrates that P2X7 receptor in BM-derived cells plays a critical role in the
      progression of severe TB.

PMID- 28450869
TI  - HiJAKing Innate Lymphoid Cells?

PMID- 28450868
TI  - Hepatitis B Virus Immunopathology, Model Systems, and Current Therapies.
AB  - Most people develop acute hepatitis B virus (HBV)-related hepatitis that is
      controlled by both humoral and cellular immune responses following acute
      infection. However, a number of individuals in HBV-endemic areas fail to resolve
      the infection and consequently become chronic carriers. While a vaccine is
      available and new antiviral drugs are being developed, elimination of
      persistently infected cells is still a major issue. Standard treatment in HBV
      infection includes IFN-alpha, nucleoside, or nucleotide analogs, which has direct
      antiviral activity and immune modulatory capacities. However, immunological
      control of the virus is often not durable. A robust T-cell response is associated
      with control of HBV infection and liver damage; however, HBV-specific T cells are
      deleted, dysfunctional, or become exhausted in chronic hepatitis patients. As a
      result, efforts to restore virus-specific T-cell immunity in chronic HBV patients
      using antiviral therapy, immunomodulatory cytokines, or therapeutic vaccination
      have had little success. Adoptive cell transfer of T cells with specificity for
      HBV antigen+ cells represents an approach aiming to ultimately eliminate residual
      hepatocytes carrying HBV covalently closed circular DNA (cccDNA). Here, we
      discuss recent findings describing HBV immunopathology, model systems, and
      current therapies.

PMID- 28450870
TI  - Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil
      Cytoplasmic Antibodies.
AB  - Neutrophil extracellular traps (NETs) are chromatin filaments decorated with
      enzymes from neutrophil cytoplasmic granules. Anti-neutrophil cytoplasmic
      antibodies (ANCAs) bind to enzymes from neutrophil cytoplasmic granules and are
      biomarkers for the diagnosis of systemic vasculitides. ANCA diagnostics are based
      on indirect immunofluorescence (IIF) of ethanol-fixed neutrophils. IIF shows a
      cytoplasmic staining pattern (C-ANCA) due to autoantibodies against proteinase 3
      (PR3) or a perinuclear staining pattern (P-ANCA) due to autoantibodies against
      myeloperoxidase (MPO). The distinct ANCA-staining patterns are an artifact of
      ethanol fixation. Here, we tested NETs as a substrate for the detection of ANCAs
      in human sera. We observed that P-ANCAs specifically stained NETs, while C-ANCAs
      targeted the cell bodies of netting neutrophils. The distinct ANCA-staining
      patterns were caused by the presence of MPO, but not PR3, in NETs. Using NETs as
      a substrate for IIF, we characterized ANCAs in sera of patients with ANCA
      associated vasculitis (AAV). Furthermore, we inhibited serine proteases by
      diisopropylfluorophosphate to prevent chromatin unfolding and the release of NETs
      and thus generated neutrophils with MPO-positive nuclei and PR3-positive
      cytoplasm, which resembled the appearance of ethanol-fixed neutrophils. In
      conclusion, our data suggest that NETs are selectively loaded with antigens
      recognized by P-ANCAs, and netting neutrophils provide a physiological substrate
      for ANCA detection in patients with AAV.

PMID- 28450871
TI  - Rubisco and Rubisco Activase Play an Important Role in the Biochemical
      Limitations of Photosynthesis in Rice, Wheat, and Maize under High Temperature
      and Water Deficit.
AB  - To understand the effect of heat and drought on three major cereal crops, the
      physiological and biochemical (i.e., metabolic) factors affecting photosynthesis
      were examined in rice, wheat, and maize plants grown under long-term water
      deficit (WD), high temperature (HT) and the combination of both stresses (HT-WD).
      Diffusional limitations to photosynthesis prevailed under WD for the C3 species,
      rice and wheat. Conversely, biochemical limitations prevailed under WD for the C4
      species, maize, under HT for all three species, and under HT-WD in rice and
      maize. These biochemical limitations to photosynthesis were associated with
      Rubisco activity that was highly impaired at HT and under HT-WD in the three
      species. Decreases in Rubisco activation were unrelated to the amount of Rubisco
      and Rubisco activase (Rca), but were probably caused by inhibition of Rca
      activity, as suggested by the mutual decrease and positive correlation between
      Rubisco activation state and the rate of electron transport. Decreased Rubisco
      activation at HT was associated with biochemical limitation of net CO2
      assimilation rate (AN). Overall, the results highlight the importance of Rubisco
      as a target for improving the photosynthetic performance of these C3 (wheat and
      rice) and C4 (maize) cereal crops under increasingly variable and warmer
      climates.

PMID- 28450872
TI  - Comparative Analysis of Ralstonia solanacearum Methylomes.
AB  - Ralstonia solanacearum is an important soil-borne plant pathogen with broad
      geographical distribution and the ability to cause wilt disease in many
      agriculturally important crops. Genome sequencing of multiple R. solanacearum
      strains has identified both unique and shared genetic traits influencing their
      evolution and ability to colonize plant hosts. Previous research has shown that
      DNA methylation can drive speciation and modulate virulence in bacteria, but the
      impact of epigenetic modifications on the diversification and pathogenesis of R.
      solanacearum is unknown. Sequencing of R. solanacearum strains GMI1000 and UY031
      using Single Molecule Real-Time technology allowed us to perform a comparative
      analysis of R. solanacearum methylomes. Our analysis identified a novel
      methylation motif associated with a DNA methylase that is conserved in all
      complete Ralstonia spp. genomes and across the Burkholderiaceae, as well as a
      methylation motif associated to a phage-borne methylase unique to R. solanacearum
      UY031. Comparative analysis of the conserved methylation motif revealed that it
      is most prevalent in gene promoter regions, where it displays a high degree of
      conservation detectable through phylogenetic footprinting. Analysis of hyper- and
      hypo-methylated loci identified several genes involved in global and virulence
      regulatory functions whose expression may be modulated by DNA methylation.
      Analysis of genome-wide modification patterns identified a significant
      correlation between DNA modification and transposase genes in R. solanacearum
      UY031, driven by the presence of a high copy number of ISrso3 insertion sequences
      in this genome and pointing to a novel mechanism for regulation of transposition.
      These results set a firm foundation for experimental investigations into the role
      of DNA methylation in R. solanacearum evolution and its adaptation to different
      plants.

PMID- 28450873
TI  - A Proteome Translocation Response to Complex Desert Stress Environments in
      Perennial Phragmites Sympatric Ecotypes with Contrasting Water Availability.
AB  - After a long-term adaptation to desert environment, the perennial aquatic plant
      Phragmites communis has evolved a desert-dune ecotype. The desert-dune ecotype
      (DR) of Phragmites communis showed significant differences in water activity and
      protein distribution compared to its sympatric swamp ecotype (SR). Many proteins
      that were located in the soluble fraction of SR translocated to the insoluble
      fraction of DR, suggesting that membrane-associated proteins were greatly
      reinforced in DR. The unknown phenomenon in plant stress physiology was defined
      as a proteome translocation response. Quantitative 2D-DIGE technology highlighted
      these 'bound' proteins in DR. Fifty-eight kinds of proteins were identified as
      candidates of the translocated proteome in Phragmites. The majority were
      chloroplast proteins. Unexpectedly, Rubisco was the most abundant protein
      sequestered by DR. Rubisco activase, various chaperons and 2-cysteine
      peroxiredoxin were major components in the translocation response. Conformational
      change was assumed to be the main reason for the Rubisco translocation due to no
      primary sequence difference between DR and SR. The addition of reductant in
      extraction process partially reversed the translocation response, implying that
      intracellular redox status plays a role in the translocation response of the
      proteome. The finding emphasizes the realistic significance of the membrane
      association of biomolecule for plant long-term adaptation to complex stress
      conditions.

PMID- 28450875
TI  - Reproductive Strategies in Mediterranean Legumes: Trade-Offs between Phenology,
      Seed Size and Vigor within and between Wild and Domesticated Lupinus Species
      Collected along Aridity Gradients.
AB  - To investigate wild and domesticated Mediterranean annual reproductive
      strategies, common garden comparisons of Old World lupins collected along aridity
      gradients were initiated. These are excellent candidates for ecophysiology, being
      widely distributed across contrasting environments, having distinct domestication
      histories, from ancient Lupinus albus to recently domesticated Lupinus
      angustifolius and Lupinus luteus, facilitating the study of both natural and
      human selection. Strong trade-offs between seed size, early vigor and phenology
      were observed: vigor increasing, and flowering becoming earlier with increasing
      seed size. Despite large specific differences in all these traits, natural and
      human selection have operated in very similar ways in all 3 species. In wild
      material, as collection environments became drier and hotter, phenology became
      earlier, while seed size, early vigor and reproductive investment increased. Wild
      and domesticated germplasm separated along similar lines. Within similar
      habitats, domesticated material was consistently earlier, with larger seeds,
      greater early vigor and higher reproductive investment than wild, suggesting
      selection for both early establishment and timely maturity/drought escape in both
      domesticated and wild low rainfall ecotypes. Species differences reflected their
      distribution. Small and soft-seeded, low vigor L. luteus had a late, rainfall
      responsive phenology specifically adapted to long season environments, and a
      narrow coastal distribution. L. angustifolius was much more conservative; more
      hard-seeded, flowering and maturing much earlier, with a wide Mediterranean
      distribution. L. albus flowered earlier but matured much later, with longer
      reproductive phases supporting much larger seed sizes and early vigor than either
      L. luteus or L. angustifolius. This ruderal/competitive combination appears to
      give L. albus a broad adaptive capacity, reflected in its relatively wider
      Mediterranean/North African distribution.

PMID- 28450874
TI  - Super-resolution Microscopy - Applications in Plant Cell Research.
AB  - Most of the present knowledge about cell organization and function is based on
      molecular and genetic methods as well as cytological investigations. While
      electron microscopy allows identifying cell substructures until a resolution of
      ~1 nm, the resolution of fluorescence microscopy is restricted to ~200 nm due to
      the diffraction limit of light. However, the advantage of this technique is the
      possibility to identify and co-localize specifically labeled structures and
      molecules. The recently developed super-resolution microscopy techniques, such as
      Structured Illumination Microscopy, Photoactivated Localization Microscopy,
      Stochastic Optical Reconstruction Microscopy, and Stimulated Emission Depletion
      microscopy allow analyzing structures and molecules beyond the diffraction limit
      of light. Recently, there is an increasing application of these techniques in
      cell biology. This review evaluates and summarizes especially the data achieved
      until now in analyzing the organization and function of plant cells, chromosomes
      and interphase nuclei using super-resolution techniques.

PMID- 28450876
TI  - Bioactivity in Rhododendron: A Systemic Analysis of Antimicrobial and Cytotoxic
      Activities and Their Phylogenetic and Phytochemical Origins.
AB  - The exceptional diversity of the genus Rhododendron has a strong potential for
      identification, characterization, and production of bioactive lead compounds for
      health purposes. A particularly relevant field of application is the search for
      new antibiotics. Here, we present a comparative analysis of nearly 90
      Rhododendron species targeted toward the search for such candidate substances.
      Through a combination of phytochemical profiles with antimicrobial susceptibility
      and cytotoxicity, complemented by phylogenetic analyses, we identify seven
      potentially antimicrobial active but non-cytotoxic compounds in terms of mass-to
      charge ratios and retention times. Exemplary bioactivity-guided fractionation for
      a promising Rhododendron species experimentally supports in fact one of these
      candidate lead compounds. By combining categorical correlation analysis with
      Boolean operations, we have been able to investigate the origin of bioactive
      effects in further detail. Intriguingly, we discovered clear indications of
      systems effects (synergistic interactions and functional redundancies of
      compounds) in the manifestation of antimicrobial activities in this plant genus.

PMID- 28450877
TI  - Responses to Hypoxia and Endoplasmic Reticulum Stress Discriminate the
      Development of Vitreous and Floury Endosperms of Conventional Maize (Zea mays)
      Inbred Lines.
AB  - Major nutritional and agronomical issues relating to maize (Zea mays) grains
      depend on the vitreousness/hardness of its endosperm. To identify the
      corresponding molecular and cellular mechanisms, most studies have been conducted
      on opaque/floury mutants, and recently on Quality Protein Maize, a reversion of
      an opaque2 mutation by modifier genes. These mutant lines are far from
      conventional maize crops. Therefore, a dent and a flint inbred line were chosen
      for analysis of the transcriptome, amino acid, and sugar metabolites of
      developing central and peripheral endosperm that is, the forthcoming floury and
      vitreous regions of mature seeds, respectively. The results suggested that the
      formation of endosperm vitreousness is clearly associated with significant
      differences in the responses of the endosperm to hypoxia and endoplasmic
      reticulum stress. This occurs through a coordinated regulation of energy
      metabolism and storage protein (i.e., zein) biosynthesis during the grain-filling
      period. Indeed, genes involved in the glycolysis and tricarboxylic acid cycle are
      up-regulated in the periphery, while genes involved in alanine, sorbitol, and
      fermentative metabolisms are up-regulated in the endosperm center. This spatial
      metabolic regulation allows the production of ATP needed for the significant zein
      synthesis that occurs at the endosperm periphery; this finding agrees with the
      zein-decreasing gradient previously observed from the sub-aleurone layer to the
      endosperm center. The massive synthesis of proteins transiting through
      endoplasmic reticulum elicits the unfolded protein responses, as indicated by the
      splicing of bZip60 transcription factor. This splicing is relatively higher at
      the center of the endosperm than at its periphery. The biological responses
      associated with this developmental stress, which control the starch/protein
      balance, leading ultimately to the formation of the vitreous and floury regions
      of mature endosperm, are discussed.

PMID- 28450878
TI  - Regulation of Isoflavone Biosynthesis by miRNAs in Two Contrasting Soybean
      Genotypes at Different Seed Developmental Stages.
AB  - Owing to the presence of nutritionally important, health-promoting bioactive
      compounds, especially isoflavones, soybean has acquired the status of a
      functional food. miRNAs are tiny riboregulator of gene expression by either
      decreasing and/or increasing the expression of their corresponding target genes.
      Despite several works on identification and functional characterization of plant
      miRNAs, the role of miRNAs in the regulation of isoflavones metabolism is still a
      virgin field. In the present study, we identified a total of 31 new miRNAs along
      with their 245 putative target genes from soybean seed-specific ESTs using
      computational approach. The Kyoto Encyclopedia of Genes and Genomes pathway
      analyses indicated that miRNA putatively regulates metabolism and genetic
      information processing. Out of that, a total of 5 miRNAs (Gma-miRNA12, Gma
      miRNA24, Gma-miRNA26, Gma-miRNA28, and Gma-miRNA29) were predicted and validated
      for their probable role during isoflavone biosynthesis. We also validated their
      five target genes using RA-PCR, which is as good as 5'RLM-RACE. Temporal
      regulation [35 days after flowering, 45, 55, and 65 DAF] of miRNAs and their
      targets showed differential expression schema. Differential expression of Gma
      miR26 and Gma-miRNA28 along with their corresponding target genes
      (Glyma.10G197900 and Glyma.09G127200) showed a direct relationship with the total
      isoflavone content. Therefore, understanding the miRNA-based genetic regulation
      of isoflavone pathway would assist in selection and manipulation to get high
      performing soybean genotypes with better isoflavone yield.

PMID- 28450879
TI  - SOS1, HKT1;5, and NHX1 Synergistically Modulate Na+ Homeostasis in the Halophytic
      Grass Puccinellia tenuiflora.
AB  - Puccinellia tenuiflora is a typical salt-excluding halophytic grass with
      excellent salt tolerance. Plasma membrane Na+/H+ transporter SOS1, HKT-type
      protein and tonoplast Na+/H+ antiporter NHX1 are key Na+ transporters involved in
      plant salt tolerance. Based on our previous research, we had proposed a function
      model for these transporters in Na+ homeostasis according to the expression of
      PtSOS1 and Na+, K+ levels in P. tenuiflora responding to salt stress. Here, we
      analyzed the expression patterns of PtSOS1, PtHKT1;5, and PtNHX1 in P. tenuiflora
      under 25 and 150 mM NaCl to further validate this model by combining previous
      physiological characteristics. Results showed that the expressions of PtSOS1 and
      PtHKT1;5 in roots were significantly induced and peaked at 6 h under both 25 and
      150 mM NaCl. Compared to the control, the expression of PtSOS1 significantly
      increased by 5.8-folds, while that of PtHKT1;5 increased only by 1.2-folds in
      roots under 25 mM NaCl; on the contrary, the expression of PtSOS1 increased by
      1.4-folds, whereas that of PtHKT1;5 increased by 2.2-folds in roots under 150 mM
      NaCl. In addition, PtNHX1 was induced instantaneously under 25 mM NaCl, while its
      expression was much higher and more persistent in shoots under 150 mM NaCl. These
      results provide stronger evidences for the previous hypothesis and extend the
      model which highlights that SOS1, HKT1;5, and NHX1 synergistically regulate Na+
      homeostasis by controlling Na+ transport systems at the whole-plant level under
      both lower and higher salt conditions. Under mild salinity, PtNHX1 in shoots
      compartmentalized Na+ into vacuole slowly, and vacuole potential capacity for
      sequestering Na+ would enhance Na+ loading into the xylem of roots by PtSOS1
      through feedback regulation; and consequently, Na+ could be transported from
      roots to shoots by transpiration stream for osmotic adjustment. While under
      severe salinity, Na+ was rapidly sequestrated into vacuoles of mesophyll cells by
      PtNHX1 and the vacuole capacity became saturated for sequestering more Na+, which
      in turn regulated long-distance Na+ transport from roots to shoots. As a result,
      the expression of PtHKT1;5 was strongly induced so that the excessive Na+ was
      unloaded from xylem into xylem parenchyma cells by PtHKT1;5.

PMID- 28450880
TI  - Development of Molecular Markers for Iron Metabolism Related Genes in Lentil and
      Their Expression Analysis under Excess Iron Stress.
AB  - Multiple genes and transcription factors are involved in the uptake and
      translocation of iron in plants from soil. The sequence information about iron
      uptake and translocation related genes is largely unknown in lentil (Lens
      culinaris Medik.). This study was designed to develop iron metabolism related
      molecular markers for Ferritin-1, BHLH-1 (Basic helix loop helix), or FER-like
      transcription factor protein and IRT-1 (Iron related transporter) genes using
      genome synteny with barrel medic (Medicago truncatula). The second objective of
      this study was to analyze differential gene expression under excess iron over
      time (2 h, 8 h, 24 h). Specific molecular markers were developed for iron
      metabolism related genes (Ferritin-1, BHLH-1, IRT-1) and validated in lentil.
      Gene specific markers for Ferritin-1 and IRT-1 were used for quantitative PCR
      (qPCR) studies based on their amplification efficiency. Significant differential
      expression of Ferritin-1 and IRT-1 was observed under excess iron conditions
      through qPCR based gene expression analysis. Regulation of iron uptake and
      translocation in lentil needs further characterization. Greater emphasis should
      be given to development of conditions simulating field conditions under external
      iron supply and considering adult plant physiology.

PMID- 28450882
TI  - Oral beta-hydroxybutyrate increases ketonemia, decreases visceral adipocyte
      volume and improves serum lipid profile in Wistar rats.
AB  - BACKGROUND: Ketosis can be induced in humans and in animals by fasting or dietary
      interventions, such as ketogenic diets. However, the increasing interest on the
      ketogenic state has motivated the development of alternative approaches to
      rapidly increase ketonemia using less drastic interventions. Here, it was tested
      whether oral intake of a beta-hydroxybutyrate (betaHB) mineral salt mixture could
      increase ketonemia in Wistar rats without any other dietary changes, thereby
      being a useful model to study ketones effects alone on metabolism. METHODS:
      betaHB salts were orally administered to provoke elevation in the ketonemia.
      Effects of this intervention were tested acutely (by gavage) and chronically (4
      weeks in drinking water). Acutely, a concomitant glucose overload was used to
      suppress endogenous ketogenesis and verify whether betaHB salts were really
      absorbed or not. Long-term administration allowed to weekly evaluate the impact
      on ketonemia, blood glucose and, after 4 weeks, on body weight, visceral fat
      mass, lipid blood profile, serum lipolysis products and adiponectinemia. RESULTS:
      betaHB salts increased ketonemia in acute and long-term administrations, improved
      blood lipid profile by raising HDL-cholesterol concentration and decreasing
      LDL/HDL ratio, while reduced visceral adipocyte volume. Mean ketonemia correlated
      positively with HDLc and negatively with adipocyte volume and serum lipolysis
      products. CONCLUSIONS: Oral betaHB can rapidly increase ketonemia and, therefore,
      be used as an acute and long-term animal model of ketosis. Long-term treatment
      points to important beneficial effects of ketone bodies in serum lipid
      concentrations and visceral fat mass. These results may help to explain the
      metabolic adaptations following ketogenic diets, such as a better body fat
      control and a serum lipid profile improvement.

PMID- 28450883
TI  - Use of ultrasonication to increase germination rates of Arabidopsis seeds.
AB  - BACKGROUND: Arabidopsis thaliana is widely used as model organism in plant
      biology. Although not of agronomic significance, it offers important advantages
      for basic research in genetics and molecular biology including the availability
      of a large number of mutants and genetically modified lines. However, Arabidopsis
      seed longevity is limited and seeds stored for more than 10 years usually show a
      very low capacity for germination. RESULTS: The influence of ultrasonic
      stimulation was investigated on the germination of A. thaliana L. seeds. All
      experiments have been performed using a frequency of 45 kHz at constant
      temperature (24  degrees C). No germination rate differences were observed when
      using freshly collected seeds. However, using artificially deteriorated seeds,
      our results show that short ultrasonic stimulation (<1 min) significantly
      increased germination. Ultrasonic stimulation application of 30 s is the optimal
      treatment. A significant increase in the germination rate was also verified in
      naturally aged seeds after ultrasonic stimulation. Scanning electron microscopy
      observations showed an increase in the presence of pores in the seed coat after
      sonication that may be the cause, at least in part, of the increase in
      germination. The ultrasound treated seeds developed normally to mature fertile
      plants. CONCLUSIONS: Ultrasound technology can be used to enhance the germination
      process of old Arabidopsis seeds without negatively affecting seedling
      development. This effect seems to be, at least in part, due to the opening of
      pores in the seed coat. The use of ultrasonic stimulation in Arabidopsis seeds
      may contribute to the recovering of long time stored lines.

PMID- 28450881
TI  - LINE Insertion Polymorphisms are Abundant but at Low Frequencies across
      Populations of Anolis carolinensis.
AB  - Vertebrate genomes differ considerably in size and structure. Among the features
      that show the most variation is the abundance of Long Interspersed Nuclear
      Elements (LINEs). Mammalian genomes contain 100,000s LINEs that belong to a
      single clade, L1, and in most species a single family is usually active at a
      time. In contrast, non-mammalian vertebrates (fish, amphibians and reptiles)
      contain multiple active families, belonging to several clades, but each of them
      is represented by a small number of recently inserted copies. It is unclear why
      vertebrate genomes harbor such drastic differences in LINE composition. To
      address this issue, we conducted whole genome resequencing to investigate the
      population genomics of LINEs across 13 genomes of the lizard Anolis carolinensis
      sampled from two geographically and genetically distinct populations in the
      Eastern Florida and the Gulf Atlantic regions of the United States. We used the
      Mobile Element Locator Tool to identify and genotype polymorphic insertions from
      five major clades of LINEs (CR1, L1, L2, RTE and R4) and the 41 subfamilies that
      constitute them. Across these groups we found large variation in the frequency of
      polymorphic insertions and the observed length distributions of these insertions,
      suggesting these groups vary in their activity and how frequently they
      successfully generate full-length, potentially active copies. Though we found an
      abundance of polymorphic insertions (over 45,000) most of these were observed at
      low frequencies and typically appeared as singletons. Site frequency spectra for
      most LINEs showed a significant shift toward low frequency alleles compared to
      the spectra observed for total genomic single nucleotide polymorphisms. Using
      Tajima's D, FST and the mean number of pairwise differences in LINE insertion
      polymorphisms, we found evidence that negative selection is acting on LINE
      families in a length-dependent manner, its effects being stronger in the larger
      Eastern Florida population. Our results suggest that a large effective population
      size and negative selection limit the expansion of polymorphic LINE insertions
      across these populations and that the probability of LINE polymorphisms reaching
      fixation is extremely low.

PMID- 28450884
TI  - Identification of anti-HBV activities in Paeonia suffruticosa Andr. using GRP78
      as a drug target on Herbochip(r).
AB  - BACKGROUND: Herbochip(r) technology is a high throughput drug screening platform
      in a reverse screening manner, in which potential chemical leads in herbal
      extracts are immobilized and drug target proteins can be used as probes for
      screening process [BMC Complementary and Alternative Medicine (2015) 15:146].
      While herbal medicines represent an ideal reservoir for drug screenings, here a
      molecular chaperone GRP78 is demonstrated to serve as a potential target for
      antiviral drug discovery. METHODS: We cloned and expressed a truncated but fully
      functional form of human GRP78 (hGRP781-508) and used it as a probe for anti-HBV
      drug screening on herbochips. In vitro cytotoxicity and in vitro anti-HBV
      activity of the herbal extracts were evaluated by MTT and ELISA assays,
      respectively. Finally, anti-HBV activity was confirmed by in vivo assay using
      DHBV DNA levels in DHBV-infected ducklings as a model. RESULTS: Primary
      screenings using GRP78 on 40 herbochips revealed 11 positives. Four of the
      positives, namely Dioscorea bulbifera, Lasiosphaera fenzlii, Paeonia suffruticosa
      and Polygonum cuspidatum were subjected to subsequent assays. None of the above
      extracts was cytotoxic to AML12 cells, but P. cuspidatum extract (PCE) was found
      to be cytotoxic to HepG2 2.2.15 cells. Both PCE and P. suffruticosa extract (PSE)
      suppressed secretion of HBsAg and HBeAg in HepG2 2.2.15 cells. The anti-HBV
      activity of PSE was further confirmed in vivo. CONCLUSION: We have demonstrated
      that GRP78 is a valid probe for anti-HBV drug screening on herbochips. We have
      also shown that PSE, while being non-cytotoxic, possesses in vitro and in vivo
      anti-HBV activities. Taken together, our data suggest that PSE may be a potential
      anti-HBV agent for therapeutic use.

PMID- 28450885
TI  - Measurement invariance of the Hopkins Symptoms Checklist: a novel multigroup
      alignment analytic approach to a large epidemiological sample across eight
      conflict-affected districts from a nation-wide survey in Sri Lanka.
AB  - BACKGROUND: The alignment method, a novel psychometric approach, represents a
      more flexible procedure for establishing measurement invariance in
      geographically, ethnically, or linguistically diverse samples, especially in
      large epidemiological surveys. Although the Hopkins Symptoms Checklist (HSCL-25)
      has been used extensively in the field to assess anxiety and depressive symptoms,
      questions remain about the comparability of findings when the instrument is
      applied across regions in large-scale national surveys. METHODS: The present
      study is the first in the field to apply the alignment method to test the
      structure and measurement invariance of the anxiety and depression dimensions of
      the HSCL-25 amongst Sri Lankan subpopulations (n = 8456) stratified by
      geographical regions, levels of past exposure to conflict, and ethnic
      composition. RESULTS: Multigroup CFA analysis yielded non-converging models
      requiring substantial modifications to the models. As a result, multigroup
      alignment analysis was applied and the results supported the bifactorial
      structure and measurement invariance of the HSCL-25 across eight (severe and
      moderate) conflict-affected districts. The alignment analysis based on a good
      fitting configural model yielded a metric non-invariance of 22.22% and scalar non
      invariance of 5.88% (both under the established 25% threshold). The bifactorial
      model outperformed the tripartite and other models. In comparison to the anxiety
      items, the depressive items showed higher levels of metric non-invariance across
      districts. CONCLUSIONS: Our findings demonstrate the methodological feasibility
      of applying the alignment method to test the structure and invariance of the HSCL
      across ethnically diverse populations living in conflict-affected districts in
      Sri Lanka. Further studies are needed to examine ethnicity and language factors
      more critically.

PMID- 28450886
TI  - Moderate alkali-thermophilic ethanologenesis by locally isolated Bacillus
      licheniformis from Pakistan employing sugarcane bagasse: a comparative aspect of
      aseptic and non-aseptic fermentations.
AB  - BACKGROUND: Biofuels obtained from first-generation (1G) sugars-starch streams
      have been proven unsustainable as their constant consumption is not only
      significantly costly for commercial scale production systems, but it could
      potentially lead to problems associated with extortionate food items for human
      usage. In this regard, biofuels' production in alkali-thermophilic environs from
      second-generation (2G) bio-waste would not only be markedly feasible, but these
      extreme conditions might be able to sustain aseptic fermentations without
      spending much for sterilization. RESULTS: Present investigation deals with the
      valuation of ethanologenic potential of locally isolated moderate alkali
      thermophilic fermentative bacterium, Bacillus licheniformis KU886221 employing
      sugarcane cane bagasse (SCB) as substrate. A standard 2-factor central composite
      response surface design was used to estimate the optimized cellulolytic and
      hemicellulolytic enzymatic hydrolysis of SCB into maximum fermentable sugars.
      After elucidation of optimized levels of fermentation factors affecting ethanol
      fermentation using Taguchi OA L27 (3^13) experimental design, free cell batch
      culture was carried out in bench-scale stirred-tank bioreactor for ethanol
      fermentation. Succeeding fermentation modifications included subsequent substrate
      addition, immobilized cells fibrous-bed bioreactor (FBB) incorporation to the
      basic setup, and performance of in situ gas stripping for attaining improved
      ethanol yield. Highest ethanol yield of 1.1406 mol ethanol/mol of equivalent
      sugars consumed was obtained when gas stripping was performed during fed-batch
      fermentation involving FBB under aseptic conditions. Despite the fact that under
      non-aseptic conditions, 30.5% lesser ethanol was formed, still, reduced yield
      might be considered influential as it saved the cost of sterilization for ethanol
      production. CONCLUSION: Effectual utilization of low-priced abundantly available
      lignocellulosic waste sugarcane bagasse under non-aseptic moderate alkali
      thermophilic fermentation conditions as directed in this study has appeared very
      promising for large-scale cost-effective bioethanol generation processes.

PMID- 28450887
TI  - Process relevant screening of cellulolytic organisms for consolidated
      bioprocessing.
AB  - BACKGROUND: Although the biocatalytic conversion of cellulosic biomass could
      replace fossil oil for the production of various compounds, it is often not
      economically viable due to the high costs of cellulolytic enzymes. One
      possibility to reduce costs is consolidated bioprocessing (CBP), integrating
      cellulase production, hydrolysis of cellulose, and the fermentation of the
      released sugars to the desired product into one process step. To establish such a
      process, the most suitable cellulase-producing organism has to be identified.
      Thereby, it is crucial to evaluate the candidates under target process
      conditions. In this work, the chosen model process was the conversion of
      cellulose to the platform chemical itaconic acid by a mixed culture of a
      cellulolytic fungus with Aspergillus terreus as itaconic acid producer. Various
      cellulase producers were analyzed by the introduced freeze assay that measures
      the initial carbon release rate, quantifying initial cellulase activity under
      target process conditions. Promising candidates were then characterized online by
      monitoring their respiration activity metabolizing cellulose to assess the growth
      and enzyme production dynamics. RESULTS: The screening of five different
      cellulase producers with the freeze assay identified Trichoderma reesei and
      Penicillium verruculosum as most promising. The measurement of the respiration
      activity revealed a retarded induction of cellulase production for P.
      verruculosum but a similar cellulase production rate afterwards, compared to T.
      reesei. The freeze assay measurement depicted that P. verruculosum reaches the
      highest initial carbon release rate among all investigated cellulase producers.
      After a modification of the cultivation procedure, these results were confirmed
      by the respiration activity measurement. To compare both methods, a correlation
      between the measured respiration activity and the initial carbon release rate of
      the freeze assay was introduced. The analysis revealed that the different initial
      enzyme/cellulose ratios as well as a discrepancy in cellulose digestibility are
      the main differences between the two approaches. CONCLUSIONS: With two
      complementary methods to quantify cellulase activity and the dynamics of
      cellulase production for CBP applications, T. reesei and P. verruculosum were
      identified as compatible candidates for the chosen model process. The presented
      methods can easily be adapted to screen for suitable cellulose degrading
      organisms for various other applications.

PMID- 28450888
TI  - Metabolic engineering strategies for optimizing acetate reduction, ethanol yield
      and osmotolerance in Saccharomyces cerevisiae.
AB  - BACKGROUND: Glycerol, whose formation contributes to cellular redox balancing and
      osmoregulation in Saccharomyces cerevisiae, is an important by-product of yeast
      based bioethanol production. Replacing the glycerol pathway by an engineered
      pathway for NAD+-dependent acetate reduction has been shown to improve ethanol
      yields and contribute to detoxification of acetate-containing media. However, the
      osmosensitivity of glycerol non-producing strains limits their applicability in
      high-osmolarity industrial processes. This study explores engineering strategies
      for minimizing glycerol production by acetate-reducing strains, while retaining
      osmotolerance. RESULTS: GPD2 encodes one of two S. cerevisiae isoenzymes of NAD+
      dependent glycerol-3-phosphate dehydrogenase (G3PDH). Its deletion in an acetate
      reducing strain yielded a fourfold lower glycerol production in anaerobic, low
      osmolarity cultures but hardly affected glycerol production at high osmolarity.
      Replacement of both native G3PDHs by an archaeal NADP+-preferring enzyme,
      combined with deletion of ALD6, yielded an acetate-reducing strain the phenotype
      of which resembled that of a glycerol-negative gpd1Delta gpd2Delta strain in low
      osmolarity cultures. This strain grew anaerobically at high osmolarity (1 mol L-1
      glucose), while consuming acetate and producing virtually no extracellular
      glycerol. Its ethanol yield in high-osmolarity cultures was 13% higher than that
      of an acetate-reducing strain expressing the native glycerol pathway.
      CONCLUSIONS: Deletion of GPD2 provides an attractive strategy for improving
      product yields of acetate-reducing S. cerevisiae strains in low, but not in high
      osmolarity media. Replacement of the native yeast G3PDHs by a heterologous NADP+
      preferring enzyme, combined with deletion of ALD6, virtually eliminated glycerol
      production in high-osmolarity cultures while enabling efficient reduction of
      acetate to ethanol. After further optimization of growth kinetics, this strategy
      for uncoupling the roles of glycerol formation in redox homeostasis and
      osmotolerance can be applicable for improving performance of industrial strains
      in high-gravity acetate-containing processes.

PMID- 28450889
TI  - Identification of mosaic and segmental aneuploidies by next-generation sequencing
      in preimplantation genetic screening can improve clinical outcomes compared to
      array-comparative genomic hybridization.
AB  - BACKGROUND: Chromosomal mosaicism is observed as the presence of both euploid and
      aneuploid cells in a particular blastocyst. Recent studies have reported that the
      implantation rate of mosaic embryo transfer is remarkably lower than the euploid
      embryos. The superior capability of next-generation sequencing (NGS) to detect
      chromosomal mosaicism in preimplantation genetic screening (PGS) remains
      controversial, and several data displayed similar implantation and pregnancy
      rates using NGS or array comparative genomic hybridization (aCGH). RESULTS: In
      this study, the main inconsistency of aneuploidy detection and clinical
      performance between the NGS and aCGH were assessed. The phase I consisted of a
      parallel comparison in 182 blastocysts from 45 selected PGS patients for both the
      NGS and aCGH platforms. The phase II retrospectively compared the clinical
      outcomes of 90 patients with NGS-screened euploid embryo transfer to that of 129
      patients with aCGH-screened euploid embryo transfer. The parallel comparison
      showed that the inconsistency of embryo euploidy was 11.8% (p = 0.01).
      Chromosomal mosaicism (10.7% with NGS vs. 3.9% with aCGH) and segmental
      aneuploidy (10.7% with NGS vs. 6.7% with aCGH) contributed to the discrepancy
      mainly. The chromosomally mosaic embryos (20%-50% of aneuploidy) and several
      embryos with segmental aneuploidy (>=10 Mbp) were hard to distinguish using the
      aCGH platform, but could be clearly identified using the NGS platform. After the
      first euploid embryo cryotransfer, the beta-HCG(+) rate and implantation rate
      significantly increased in the PGS/NGS patients (HCG[+] rate: 73.3% in PGS/NGS
      vs. 60.5% in PGS/aCGH, p = 0.048; implantation rate: 53.2% in PGS/NGS vs. 45.0%
      in PGS/aCGH, p = 0.043). The clinical and ongoing pregnancy rates appeared higher
      in the NGS group, but did not reached statistical significance. CONCLUSIONS: The
      results demonstrated that the NGS platform can identify embryos with chromosomal
      mosaicism and segmental aneuploidy more precisely than the aCGH platform, and the
      following clinical performance of NGS was more favorable.

PMID- 28450890
TI  - Multi-class computational evolution: development, benchmark evaluation and
      application to RNA-Seq biomarker discovery.
AB  - BACKGROUND: A computational evolution system (CES) is a knowledge discovery
      engine that can identify subtle, synergistic relationships in large datasets.
      Pareto optimization allows CESs to balance accuracy with model complexity when
      evolving classifiers. Using Pareto optimization, a CES is able to identify a very
      small number of features while maintaining high classification accuracy. A CES
      can be designed for various types of data, and the user can exploit expert
      knowledge about the classification problem in order to improve discrimination
      between classes. These characteristics give CES an advantage over other
      classification and feature selection algorithms, particularly when the goal is to
      identify a small number of highly relevant, non-redundant biomarkers. Previously,
      CESs have been developed only for binary class datasets. In this study, we
      developed a multi-class CES. RESULTS: The multi-class CES was compared to three
      common feature selection and classification algorithms: support vector machine
      (SVM), random k-nearest neighbor (RKNN), and random forest (RF). The algorithms
      were evaluated on three distinct multi-class RNA sequencing datasets. The
      comparison criteria were run-time, classification accuracy, number of selected
      features, and stability of selected feature set (as measured by the Tanimoto
      distance). The performance of each algorithm was data-dependent. CES performed
      best on the dataset with the smallest sample size, indicating that CES has a
      unique advantage since the accuracy of most classification methods suffer when
      sample size is small. CONCLUSION: The multi-class extension of CES increases the
      appeal of its application to complex, multi-class datasets in order to identify
      important biomarkers and features.

PMID- 28450893
TI  - Reliability and validity of the Attributional Style Questionnaire- Survey in
      people with multiple sclerosis.
AB  - BACKGROUND: The current study aimed to examine the psychometric properties of an
      attributional style measure that can be administered remotely, to people who have
      multiple sclerosis (MS). METHODS: A total of 495 participants with MS were
      recruited. Participants completed the Attributional Style Questionnaire-Survey
      (ASQ-S) and two comparison measures of cognitive variables via postal survey on
      three occasions, each 12 months apart. Internal reliability, test-retest
      reliability and congruent validity were considered. RESULTS: The internal
      reliability of the ASQ-S was good (alpha > 0.7). The test-retest correlations
      were significant, but failed to reach the 0.7 set. The congruent validity of the
      ASQ-S was established relative to the comparisons. CONCLUSIONS: The psychometric
      properties of the ASQ-S indicate that it shows promise as a tool for researchers
      investigating depression in people with MS and is likely sound to use clinically
      in this population.

PMID- 28450891
TI  - Adrenocorticotropic hormone versus methylprednisolone added to interferon beta in
      patients with multiple sclerosis experiencing breakthrough disease: a randomized,
      rater-blinded trial.
AB  - BACKGROUND: The objective of this study was to evaluate monthly intramuscular
      adrenocorticotropic hormone (ACTH) gel versus intravenous methylprednisolone
      (IVMP) add-on therapy to interferon beta for breakthrough disease in patients
      with relapsing forms of multiple sclerosis. METHODS: This was a prospective, open
      label, examiner-blinded, 15-month pilot study evaluating patients with Expanded
      Disability Status Scale (EDSS) score 3.0-6.5 and at least one clinical relapse or
      new T2 or gadolinium-enhanced lesion in the previous year. Twenty-three patients
      were randomized to ACTH (n = 12) or IVMP (n = 11) and completed the study. The
      primary outcome measure was the cumulative number of relapses. Secondary outcomes
      included EDSS, Mental Health Inventory (MHI), plasma cytokines, MS Functional
      Composite (MSFC), Quality-of-Life (MS-QOL) score, bone mineral density (BMD), and
      new or worsened psychiatric symptoms per month. Brain magnetic resonance imaging
      was analyzed post hoc. This was a preliminary and small-scale study. RESULTS:
      Relapse rates differed significantly [ACTH 0.08, 95% confidence interval (CI)
      0.01-0.54 versus IVMP 0.80, 95% CI 0.36-1.75; rate ratio, IVMP versus ACTH: 9.56,
      95% CI 1.23-74.6; p = 0.03]. ACTH improved (p = 0.03) MHI (slope 0.95 +/- 0.38
      points/month; p = 0.02 versus slope -0.38 +/- 0.43 points/month; p = 0.39). On
      study decreases (all p < 0.05) in eight cytokine levels occurred only in the ACTH
      group. However, on-study EDSS, MSFC, MS-QOL, BMD, and MRI lesion changes were not
      significant between groups. Psychiatric symptoms per patient were greater with
      IVMP than ACTH (0.55, 95% CI 0.12-2.6 versus 0; p < 0.0001). Other common adverse
      events were insomnia and urinary tract infections (IVMP, seven events each) and
      fatigue or flu symptoms (ACTH, five events each). CONCLUSIONS: This study
      provided class II evidence that ACTH produced better examiner-assessed cumulative
      rates of relapses per patient than IVMP in the adjunctive treatment of
      breakthrough disease in multiple sclerosis.

PMID- 28450892
TI  - Cognition and fatigue in patients with relapsing multiple sclerosis treated by
      subcutaneous interferon beta-1a: an observational study SKORE.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the
      central nervous system, which often causes progressive neurological disability.
      In addition to motor and sensory dysfunction, cognitive decline and fatigue are
      frequent manifestations of the disease. Fatigue is probably the most common
      symptom, with up to 90% of MS individuals reporting fatigue at some point.
      Cognitive impairment affects about 50% of patients and may be present at all MS
      stages. The aim of this observational study was to evaluate changes in cognition,
      fatigue, and disability status in 300 relapsing-remitting MS (RRMS) patients,
      treated with subcutaneous (sc) interferon (IFN) beta-1a over 2 years. METHODS:
      The study was designed as an observational, multicentre, prospective, single-arm,
      phase IV study carried out in 13 MS centres in the Czech Republic. Cognition
      status was assessed using the Paced Auditory Serial Addition Task (PASAT),
      fatigue using the Fatigue Descriptive Scale (FDS), and disability using the
      Expanded Disability Status Scale (EDSS), at baseline, and after 6, 12 and 24
      months. The percentage of patients with changed versus stable cognition, fatigue
      status and disability was calculated at each time point and the changes in these
      scores were evaluated. RESULTS: The proportion of patients with cognitive
      improvement was higher compared with those with a stable or decreased PASAT
      scores at all time points, and the average cognitive performance improved during
      the follow-up period. Also the proportion of patients with stable or improved
      fatigue and EDSS scores was higher compared with those in which FDS or EDSS
      scores declined, this was found at all time points of the analysed sample.
      However, the direct effect of IFN beta-1a on cognition and fatigue cannot be
      concluded from this study. CONCLUSIONS: The results of this observational study
      have demonstrated a stable or improved cognitive performance, fatigue status, and
      disability level in the majority of RRMS patients treated with sc IFN beta-1a
      over a two-year follow-up period, in a real life setting, in the Czech Republic.

PMID- 28450894
TI  - Peginterferon beta-1a reduces disability worsening in relapsing-remitting
      multiple sclerosis: 2-year results from ADVANCE.
AB  - BACKGROUND: In the pivotal phase III 2-year ADVANCE study, subcutaneous
      peginterferon beta-1a 125 mcg every 2 weeks demonstrated significant improvements
      in clinical outcomes, including disability endpoints, in patients with relapsing
      remitting multiple sclerosis (RRMS). Here, we aim to further evaluate disability
      data from ADVANCE, and explore associations between confirmed disability
      progression (CDP), functional status, and health-related quality of life (HRQoL).
      METHODS: In total, 1512 patients were randomized to placebo or peginterferon beta
      1a 125 mcg every 2 or 4 weeks. After 1 year, patients on placebo were re
      randomized to peginterferon beta-1a every 2 or 4 weeks. CDP was defined as ?1.0
      point increase from a baseline Expanded Disability Status Scale (EDSS) score ?
      1.0, or ?1.5-point increase from baseline 0, confirmed 12 or 24 weeks after
      onset. RESULTS: Peginterferon beta-1a every 2 weeks significantly reduced risk of
      12- and 24-week CDP at 1 year compared with placebo (12-week CDP: 6.8% versus
      10.5%, p = 0.038; 24-week CDP: 4% versus 8.4%, p = 0.0069, peginterferon beta-1a
      every 2 weeks versus placebo, respectively). Benefits were maintained over 2
      years (11.2% and 7.7%, peginterferon beta-1a every 2 weeks in 12- and 24-week
      CDP, respectively). Approximately 90% of patients with 24-week CDP had
      simultaneous worsening by ?1 point in at least one functional system score, most
      commonly pyramidal. Displaying a 24-week CDP was associated with worse scores on
      the Multiple Sclerosis Functional Composite (MSFC) scale and several HRQoL
      instruments; the impact of CDP was attenuated by treatment with peginterferon
      beta-1a every 2 weeks. CONCLUSIONS: Peginterferon beta-1a has the potential to
      prevent/delay worsening of disability in patients with relapsing-remitting
      multiple sclerosis. Furthermore, improved benefits in disability status with
      peginterferon beta-1a were also associated with improved functional status and
      HRQoL [ClinicalTrials.gov identifier: NCT00906399].

PMID- 28450896
TI  - Daclizumab high-yield process in the treatment of relapsing-remitting multiple
      sclerosis.
AB  - Daclizumab is a humanized monoclonal antibody that binds to the alpha subunit
      (CD25) of the interleukin-2 receptor and favorably modulates the immune
      environment in multiple sclerosis (MS). Blockage of CD25, among other effects,
      causes expansion and enhanced function of regulatory CD56bright natural killer
      cells, which seems to be the leading mechanism of action in MS. Phase II and III
      clinical trials have demonstrated that monthly subcutaneous injections of
      daclizumab high yield process (DAC HYP) 150 mg in patients with relapsing MS led
      to a significant reduction of annualized relapse rate and decreased number of
      contrast-enhanced lesions on brain magnetic resonance imaging. Treatment with DAC
      HYP had efficacy superior to treatment with weekly injections of interferon
      beta1a. This review summarizes the development of and clinical experience with
      daclizumab in MS.

PMID- 28450895
TI  - Targeting B cells in relapsing-remitting multiple sclerosis: from pathophysiology
      to optimal clinical management.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that is
      caused by an autoimmune response against central nervous system (CNS) structures.
      Traditionally considered a T-cell-mediated disorder, the contribution of B cells
      to the pathogenesis of MS has long been debated. Based on recent promising
      clinical results from CD20-depleting strategies by three therapeutic monoclonal
      antibodies in clinical phase II and III trials (rituximab, ocrelizumab and
      ofatumumab), targeting B cells in MS is currently attracting growing interest
      among basic researchers and clinicians. Many questions about the role of B and
      plasma cells in MS remain still unanswered, ranging from the role of specific B
      cell subsets and functions to the optimal treatment regimen of B-cell depletion
      and monitoring thereafter. Here, we will assess our current knowledge of the
      mechanisms implicating B cells in multiple steps of disease pathology and examine
      current and future therapeutic approaches for the treatment of MS.

PMID- 28450897
TI  - Plasma exchange as a cost-effective option for treating Guillain-Barre syndrome.

PMID- 28450899
TI  - Mechanisms of antidiarrhoeal effects by diosmectite in human intestinal cells.
AB  - BACKGROUND: Rotavirus (RV) induces diarrhoea through a sequence of enterotoxic
      and cytotoxic effects. The former are NSP4-dependent, induce calcium-dependent
      chloride secretion and involve oxidative stress. Diosmectite (DS) is a natural
      clay that has been recommended as an active therapy for diarrhoea, but the
      mechanism of its effect is not clear. Electrical parameters may be used to
      measure the direct enterotoxic and cytotoxic effects in polar epithelial
      intestinal cells. To investigate the effects of DS on RV-induced enterotoxic and
      cytotoxic damage. Caco-2 cells were used as a model of RV infection to evaluate
      chloride secretion, epithelial integrity, oxidative stress and viral infectivity
      in Ussing chambers. RESULTS: Diosmectite reduced the expression of NSP4 and
      oxidative stress, resulting in a strong inhibition of chloride secretion.
      Preincubating RV with DS reduced the cytotoxic effect. Finally, the viral load
      was reduced by DS but not by control clay. This result suggests that DS
      specifically affects the early events of RV infection protecting the enterocyte,
      whereas it does not restore already-established cell damage. CONCLUSION: These
      findings indicate that DS exerts an anti-diarrhoeal effect by inhibiting viral
      replication and the expression of NSP4. Both ion secretion and cell damage
      induced by RV are strongly inhibited consequent to the antiviral effect, which
      explains its clinical efficacy.

PMID- 28450898
TI  - A single-blinded, randomized, parallel group superiority trial investigating the
      effects of footwear and custom foot orthoses versus footwear alone in individuals
      with patellofemoral joint osteoarthritis: a phase II pilot trial protocol.
AB  - BACKGROUND: Patellofemoral joint osteoarthritis is a common condition, yet
      information regarding conservative management is lacking. Foot orthoses are an
      effective intervention for improving pain and function in younger individuals
      with patellofemoral pain and may be effective in those with patellofemoral
      osteoarthritis. This pilot study will seek to establish the feasibility of a
      phase III randomised controlled trial to investigate whether foot orthoses worn
      in prescribed motion controlled footwear are superior to prescribed motion
      control footwear alone in the management of patellofemoral osteoarthritis.
      METHODS/DESIGN: This phase II pilot clinical trial is designed as a randomized,
      single-blind, parallel group, two arm, superiority trial. The trial will recruit
      44 participants from Queensland and Tasmania, Australia. Volunteers aged 40 years
      and over must have clinical symptoms and radiographic evidence of patellofemoral
      osteoarthritis to be eligible for inclusion. Those eligible will be randomized to
      receive either foot orthoses and prescribed motion control shoes, or prescribed
      motion control shoes alone, to be worn for a period of 4 months. The feasibility
      of a phase III clinical trial will be evaluated by assessing factors such as
      recruitment rate, number of eligible participants, participant compliance with
      the study protocol, adverse events, and drop-out rate. A secondary aim of the
      study will be to determine completion rates and calculate effect sizes for
      patient reported outcome measures such as knee-related symptoms, function,
      quality of life, kinesiophobia, self-efficacy, general and mental health, and
      physical activity at 2 and 4 months. Primary outcomes will be reported
      descriptively while effect sizes and 95% confidence intervals will be calculated
      for the secondary outcome measures. Data will be analysed using an intention-to
      treat principle. DISCUSSION: The results of this pilot trial will help determine
      the feasibility of a phase III clinical trial investigating whether foot orthoses
      plus motion control footwear are superior to motion control footwear alone in
      individuals with patellofemoral osteoarthritis. A Phase III clinical trial will
      help guide footwear and foot orthoses recommendations in the clinical management
      of this disorder. TRIAL REGISTRATION: Retrospectively registered with the
      Australian New Zealand Clinical Trials Registry: ACTRN12615000002583. Date
      registered: 07/01/15.

PMID- 28450900
TI  - Dipeptidyl peptidase-4 levels are increased and partially related to body fat
      distribution in patients with familial partial lipodystrophy type 2.
AB  - BACKGROUND: Dipeptidyl peptidase-4 (DDP4) is an enzyme responsible for glucagon
      like peptide-1 inactivation and plays an important role in glucose metabolism.
      OBJECTIVE: The aim of this study was to evaluate DPP4 levels in patients with
      familial partial lipodystrophy type 2 (FPLD2) and correlate it with body fat
      distribution. METHODS: Fourteen patients with FPLD2 were selected to participate
      in this study and matched to a healthy control group (n = 8). All participants
      had anthropometrical data registered. Body adiposity index (BAI) was used to
      evaluate fat distribution in this population. Body fat content and distribution
      were analyzed by dual X-ray absorptiometry (DXA). Biochemical exams, including
      DPP4 levels, were performed in all individuals. RESULTS: Despite the same body
      mass index, lipodystrophic patients had a significant lower hip (median 92.0 vs
      94.5; p = 0.028), HDL cholesterol (42.6 +/- 10.4 vs 66.1 +/- 16.0; p < 0.01) and
      BAI (24.1 +/- 2.8 vs 29.0 +/- 3.7; p = 0.02), suggesting that BAI was able to
      catch differences in fat distribution between groups. On the other hand, patients
      with FPLD2 presented significant higher levels of insulin (median 11.2 vs 5.3; p
      = 0.015), triglycerides (184.9 +/- 75.4 vs 89.1 +/- 51.0; p < 0.01) and DPP4
      (4.89 +/- 0.92 vs 3.93 +/- 1.08; p = 0.04). A trend toward an inverse statistical
      significance was observed between DPP4 levels and BAI (r = -0.38; p = 0.072). In
      the lipodistrophic group, a significant correlation was found between DPP4 levels
      and percentage of total body fat (r = 0.86; p = 0.0025) and android fat (r =
      0.78; p = 0.014). CONCLUSIONS: Patients with FPLD2 exhibit an increase in DDP4
      levels in comparison to a healthy control group. The increase in the levels of
      this enzyme does not seem to be related to the diagnosis of diabetes and might be
      associated with an increase in central fat (estimated using BAI and measured
      using DXA). These results might be used to reinforce the concept that DDP4 is an
      adipokine related to central fat distribution.

PMID- 28450901
TI  - Insertion and deletion polymorphisms of the ancient AluS family in the human
      genome.
AB  - BACKGROUND: Polymorphic Alu elements account for 17% of structural variants in
      the human genome. The majority of these belong to the youngest AluY subfamilies,
      and most structural variant discovery efforts have focused on identifying Alu
      polymorphisms from these currently retrotranspositionally active subfamilies. In
      this report we analyze polymorphisms from the evolutionarily older AluS
      subfamily, whose peak activity was tens of millions of years ago. We annotate the
      AluS polymorphisms, assess their likely mechanism of origin, and evaluate their
      contribution to structural variation in the human genome. RESULTS: Of 52
      previously reported polymorphic AluS elements ascertained for this study, 48 were
      confirmed to belong to the AluS subfamily using high stringency subfamily
      classification criteria. Of these, the majority (77%, 37/48) appear to be
      deletion polymorphisms. Two polymorphic AluS elements (4%) have features of non
      classical Alu insertions and one polymorphic AluS element (2%) likely inserted by
      a mechanism involving internal priming. Seven AluS polymorphisms (15%) appear to
      have arisen by the classical target-primed reverse transcription (TPRT)
      retrotransposition mechanism. These seven TPRT products are 3' intact with 3'
      poly-A tails, and are flanked by target site duplications; L1 ORF2p endonuclease
      cleavage sites were also observed, providing additional evidence that these are
      L1 ORF2p endonuclease-mediated TPRT insertions. Further sequence analysis showed
      strong conservation of both the RNA polymerase III promoter and SRP9/14 binding
      sites, important for mediating transcription and interaction with
      retrotransposition machinery, respectively. This conservation of functional
      features implies that some of these are fairly recent insertions since they have
      not diverged significantly from their respective retrotranspositionally competent
      source elements. CONCLUSIONS: Of the polymorphic AluS elements evaluated in this
      report, 15% (7/48) have features consistent with TPRT-mediated insertion, thus
      suggesting that some AluS elements have been more active recently than previously
      thought, or that fixation of AluS insertion alleles remains incomplete. These
      data expand the potential significance of polymorphic AluS elements in
      contributing to structural variation in the human genome. Future discovery
      efforts focusing on polymorphic AluS elements are likely to identify more such
      polymorphisms, and approaches tailored to identify deletion alleles may be
      warranted.

PMID- 28450903
TI  - PCSK9 as a therapeutic target for cardiovascular disease.
AB  - It is well recognized that the elevated plasma level of low-density lipoprotein
      cholesterol (LDL-C) is a major risk factor for atherosclerosis and cardiovascular
      disease (CVD). Deposition of pro-atherogenic LDL-C, on the intima of arterial
      wall, contributes to plaque formation and atherosclerosis, which further leads to
      lowered blood flow to vital organs and increased risk of CVD. The most commonly
      used statin therapy is effective in reducing dyslipidemia and preventing
      cardiovascular events only in about half of the patient population. However, in
      patients with familial hypercholesterolemia, these drugs were not effective to
      meet the required goals of lower LDL-C, and to reduce the CVD risk. Furthermore,
      many patients even develop intolerability to statins and resistance. The
      identification of pro-protein convertase subtilisin/kexin type 9 (PCSK9) and the
      association of PCSK9 mutations with familial hypercholesterolemia led to the
      identification of PCSK9 as a new therapeutic target for lowering LDL-C and
      dyslipidemia-associated CVD. PCSK9 is found to promote the degradation of LDL
      receptor (LDLR), thus rendering it unavailable for recycling to hepatocyte plasma
      membrane, leading to elevated levels of circulating LDL-C, as it cannot be taken
      up into cells. While gain-of-function mutations aggravate the degradation of LDLR
      as in familial hypercholesterolemia whereas loss of function mutations reduce the
      ability of PCSK9 to promote the degradation of LDLR and thus lower the plasma
      level of LDL-C and dyslipidemia. Monoclonal antibodies against PCSK9 are
      currently being tested in clinical trials and are found to be efficacious in
      countering the activity of PCSK9 and thus control the plasma LDL-C and
      triglycerides even in statin non-responsive patients and protect against
      dyslipidemia-related CVD.

PMID- 28450904
TI  - CaMKII: The molecular villain that aggravates cardiovascular disease.
AB  - Pathological remodeling of the myocardium is an integral part of the events that
      lead to heart failure (HF), which involves altered gene expression, disturbed
      signaling pathways and altered Ca2+ homeostasis and the players involved in this
      process. Of particular interest is the chronic activation of Ca2+/calmodulin
      dependent protein kinase II (CaMKII) isoforms in heart, which further aggravate
      the injury to myocardium. Expression and activity of CaMKII have been found to be
      elevated in various conditions of stressed myocardium and in different heart
      diseases in both animal models as well as heart patients. CaMKII is a signaling
      molecule that regulates many cellular pathways by phosphorylating several
      proteins involved in excitation-contraction coupling and relaxation events in
      heart, cardiomyocyte apoptosis, transcriptional activation of genes related to
      cardiac hypertrophy, inflammation, and arrhythmias. CaMKII is activated by
      reactive oxygen species (ROS), which are elevated under conditions of ischemia
      reperfusion injury and in a cyclical manner, CaMKII in turn elevates ROS
      production. Both ROS and activated CaMKII increase Ca-induced Ca release from
      sarcoplasmic reticulum, which leads to cardiomyocyte membrane depolarization and
      arrhythmias. These CaMKII-mediated changes in heart ultimately culminate in
      dysfunctional myocardium and HF. Genetic studies in animal models clearly
      demonstrated that inactivation of CaMKII is protective against a variety of
      stress induced cardiac dysfunctions. Despite significant leaps in understanding
      the structural details of CaMKII, which is a very complicated and multimeric
      modular protein, currently there is no specific and potent inhibitor of this
      enzyme, that can be developed for therapeutic purposes.

PMID- 28450902
TI  - Role of neural barriers in the pathogenesis and outcome of Streptococcus
      pneumoniae meningitis.
AB  - Bacterial meningitis is an inflammatory disease of the meninges of the central
      nervous system (CNS). Streptococcus pneumoniae (S. pneumoniae), Neisseria
      meningitidis, and Haemophilus influenzae are the major bacterial pathogens
      causing meningitis with S. pneumoniae being responsible for two thirds of
      meningitis cases in the developed world. To reach the CNS following
      nasopharyngeal colonization and bacteraemia, the bacteria traverse from the
      circulation across the blood brain barrier (BBB) and choroid plexus. While the
      BBB has a protective role in healthy individuals by shielding the CNS from
      neurotoxic substances circulating in the blood and maintaining the homeostasis
      within the brain environment, dysfunction of the BBB is associated with the
      pathophysiology of numerous neurologic disorders, including bacterial meningitis.
      Inflammatory processes, including release of a broad range of cytokines and free
      radicals, further increase vascular permeability and contribute to the excessive
      neural damage observed. Injury to the cerebral microvasculature and loss of blood
      flow auto-regulation promote increased intracranial pressure and may lead to
      vascular occlusion. Other common complications commonly associated with
      meningitis include abnormal neuronal hyper-excitability (e.g., seizures) and loss
      of hearing. Despite the existence of antibiotic treatment and adjuvant therapy,
      the relatively high mortality rate and the severe outcomes among survivors of
      pneumococcal meningitis in developing and developed countries increase the
      urgency in the requirement of discovering novel biomarkers for the early
      diagnosis as well as novel treatment approaches. The present review aimed to
      explore the changes in the brain vascular barriers, which allow S. pneumoniae to
      invade the CNS, and describe the resultant brain injuries following bacterial
      meningitis.

PMID- 28450905
TI  - Protective effects of silymarin against bisphenol A-induced hepatotoxicity in
      mouse liver.
AB  - Bisphenol A (BPA) is an endocrine-disrupting chemical released into the
      environment, with severe consequences for human health, including metabolic
      syndrome and associated pathological conditions. Due to limited information on
      BPA-induced hepatotoxicity, the present study focused on investigating the
      association between BPA-induced toxicity and inflammatory markers in the liver,
      and how these injuries may be alleviated using the natural agent silymarin, a
      flavonoid with antioxidant properties obtained from Silybum marianum.
      Administration of BPA to male CD-1 mice for 10 days caused a significant increase
      in the number of cells immunopositive for interleukin 6 and tumor necrosis factor
      alpha, pro-inflammatory cytokines that mediate the hepatic inflammatory response.
      Treatment with 200 mg/kg of silymarin concurrently with BPA for 10 days resulted
      in a diminished level of pro-inflammatory cytokines and in significantly reduced
      ultrastructural injuries. Additionally, silymarin was able to restore the
      significantly decreased glycogen deposits observed following BPA exposure to
      normal levels, thus favoring hepatic glycogenesis. This study represents the
      first report of silymarin ability to reduce hepatic lesions and to counteract
      inflammation caused by BPA in mice. A dose of 200 mg/kg silymarin was sufficient
      to induce a protective effect against structural and ultrastructural injuries
      induced by BPA and to lower the levels of pro-inflammatory cytokines observed in
      murine liver tissue following exposure to BPA.

PMID- 28450906
TI  - Vascular response profiles following a nano polymer-free sirolimus-eluting stent
      implantation assessed by optical coherence tomography in a porcine model.
AB  - Optical coherence tomography (OCT) is a high resolution imaging modality and has
      been considered as the ideal tool for the evaluation of neointimal tissue and
      vascular responses following stent implantation. However, vascular response
      profiles following the implantation of a novel nano polymer-free sirolimus
      eluting stent (SES) assessed by OCT has not been fully investigated. Therefore,
      the aim of the present study was to determine the effects of a nano polymer-free
      SES on neointimal formation using OCT. A total of 16 nano polymer-free SESs were
      implanted in the coronary arteries of 8 pigs. At 3 (n=4) or 6 months (n=4), the
      animals were euthanized following OCT evaluation and the stented arterial
      segments were analyzed by histological analysis. Neointimal area, thickness and
      burden were evaluated by OCT. In addition, strut-associated inflammation, stent
      endothelialization and arterial injury were investigated by histomorphological
      analysis. OCT examination showed that at 6 months, neointimal thickness (193.3+/
      109.5 vs. 167.2+/-119.7 um, P=0.023) and neointimal burden (29.3+/-14.3 vs.
      24.8+/-17.4%, P=0.006) significantly increased compared with at 3 months.
      Histomorphological analysis indicated that the endothelialization score was
      significantly greater at 6 months compared with at 3 months (2.85+/-0.36 vs.
      2.52+/-0.60, P<0.001). However, at 3 months, nano polymer-free SES showed a
      significantly higher inflammatory score [0 (0, 1) vs. 0 (0, 0), P<0.001] compared
      with at 6 months. In conclusion, nano polymer-free SES achieves
      endothelialization at 3 months; however, neointimal proliferation is more
      significant at 6 months and may be attributed to strut-associated inflammation.

PMID- 28450907
TI  - Atorvastatin attenuates plaque vulnerability by downregulation of EMMPRIN
      expression via COX-2/PGE2 pathway.
AB  - Extracellular matrix metalloproteinase inducer (EMMPRIN) reportedly has a key
      regulatory role in matrix metalloproteinase (MMP) activities and the progression
      of atherosclerosis. Statins, which are anti-atherosclerotic pharmacological
      agents, are widely applied in clinical settings. The aim of the present study was
      to investigate the pharmaceutical effect of atorvastatin on EMMPRIN expression in
      atherosclerotic plaques. An atherosclerotic mouse model was established using
      apoliprotein E-deficient (ApoE-/-) mice raised on a high-fat diet. Additionally,
      a low (5 mg/kg/day) or high dosage (10 mg/kg/day) of atorvastatin suspension was
      administered orally for eight weeks, beginning on week 7 or 11 respectively. The
      effects of atorvastatin on atherosclerotic plaque formation and EMMPRIN
      expression were subsequently determined. The THP-1 cell line was used to
      investigate the effect of atorvastatin on EMMPRIN expression in vitro. The
      results demonstrated that the high-fat diet led to vulnerable plaques (VPs) and
      increased EMMPRIN expression in VPs in ApoE-/- mice. Atorvastatin treatment
      decreased EMMPRIN expression in the aortas and plaques of ApoE-/- mice. In vitro,
      oxidized low-density lipoprotein (ox-LDL) induced the expression of
      cyclooxygenase-2 (COX-2) and EMMPRIN in THP-1 macrophages, and atorvastatin
      inhibited ox-LDL-induced expression of PGE2, EMMPRIN and COX-2 in THP-1
      macrophages. Therefore, the present data indicated that atorvastatin treatment
      reduces the vulnerability of atherosclerotic plaques and expression of EMMPRIN,
      and that the inhibitory effect of atorvastatin on EMMPRIN may occur via the COX
      2/PGE2 signaling pathway in macrophages.

PMID- 28450908
TI  - Tailored treatment for the management of scleral necrosis following pterygium
      excision.
AB  - The present study aimed to investigate the efficacy of tailored treatment for the
      management of scleral necrosis following pterygium surgery. A series of nine
      cases of scleral necrosis following pterygium excision between September 2009 and
      September 2012 were included. In cases where ischemia was the cause of scleral
      necrosis, Tenon's membrane covering (TMC) surgery was performed. For cases with
      surgically-induced necrotizing scleritis (SINS), systemic immunosuppressive
      therapy following surgical repair of the scleral defect was administered in the
      form of oral prednisolone (starting dose, 30-60 mg/day). Five patients with
      ischemic scleral necrosis received TMC postoperatively. Four patients with SINS
      received various doses of oral prednisolone according to their systematic immune
      state. All patients had successful postoperative results except one with
      rheumatoid arthritis, who postoperatively developed scleral patch graft melting
      within 2 weeks. Following aggressive immunosuppressive treatment, the scleral
      patch graft was saved. In conclusion, patients achieved positive results using
      tailored treatment according to the pathogenesis of their scleral necrosis.

PMID- 28450909
TI  - Impact of gabapentin on neuronal high voltage-activated Ca2+ channel properties
      of injured-side axotomized and adjacent uninjured dorsal root ganglions in a rat
      model of spinal nerve ligation.
AB  - The density and properties of ion channels in the injured axon and dorsal root
      ganglion (DRG) neuronal soma membrane change following nerve injury, which may
      result in the development of neuropathic pain. Gabapentin (GBP) is a drug for the
      first-line treatment of neuropathic pain. One of its therapeutic targets is the
      voltage-activated calcium channel (VACC). In the present study, the whole-cell
      patch clamp technique was used to examine the changes of high voltage-activated
      Ca2+ (HVA-Ca2+) channels in DRG neurons from sham and neuropathic rats in the
      absence and presence of GBP. The results demonstrated a reduction in peak current
      density and the 'window current' between activation and inactivation in adjacent
      and axotomized neurons from rats that had undergone L5 spinal nerve ligation,
      thus attenuating the total inward Ca2+ current. Following the use of the specific
      channel blockers nifedipine, omega-conotoxin MVIIC and omega-conotoxin MVIIA,
      increased HVA-Ca2+ channels as well as an increased proportion of N-type Ca2+
      currents were observed in axotomized neurons. GBP inhibited HVA calcium channel
      currents in a dose-dependent manner. The activation and steady-state inactivation
      curves for HVA channels were shifted in a hyperpolarizing direction by 100 umol/l
      GBP. Following the application of GBP, a reduction in the 'window current' was
      observed in control and axotomized neurons, whereas the 'window current' was
      unchanged in adjacent neurons. This indicates that the inhibitory effects of GBP
      may be dependent on particular neuropathological or inflammatory conditions. The
      proportion of N-type Ca2+ currents and sensitivity to GBP were increased in
      axotomized neurons, which indicated the involvement of N-type Ca2+ currents in
      the inhibitory effect of GBP.

PMID- 28450910
TI  - Effect of hypoxia-inducible factor-1/vascular endothelial growth factor signaling
      pathway on spinal cord injury in rats.
AB  - The aim of the present study was to evaluate the expression of vascular
      endothelial growth factor (VEGF) and hypoxia inducible factor-1 (HIF-1), and to
      investigate the role of the HIF-1/VEGF signaling pathway following spinal cord
      injury (SCI). A total of 90 12-week-old Sprague Dawley rats were randomly divided
      into the following three groups: Sham group (operation without SCI); control
      group (SCI without ML228 treatment); and treatment group (SCI receiving ML228
      treatment). ML228 was administered as it is an activator of HIF-1alpha. The
      control and treatment groups were subjected to spinal cord hemisection and motor
      activity was evaluated using the Basso, Beattie and Bresnahan (BBB) scoring
      system. Expression of HIF-1alpha and VEGF in each injured spinal cord section was
      assessed using immunohistochemistry. Prior to SCI, there were no significant
      differences in the BBB score among the three groups (P>0.05). However, one day
      after the operation, the BBB score of the sham group was significantly higher
      than that of the other two groups (P<0.05) and the BBB scores of the control and
      treatment groups did not differ significantly (P>0.05). BBB scores 3 and 7 days
      following surgery were significantly higher in the sham group than the other two
      groups (P<0.05) and the BBB scores of the treatment group were significantly
      higher than those of the control group (P<0.05). The expression of HIF-1alpha and
      VEGF proteins in all groups were measured 1, 3 and 7 days after the operation,
      and it was observed that their expression was higher in the treatment group than
      in the control group (P<0.05). Therefore, the results of the current study
      suggest that ML228 may effectively activate the HIF-1alpha/VEGF signaling pathway
      to promote the expression of HIF-1alpha and VEGF proteins within the injured
      segment of the spinal cord, which promotes neural functional recovery following
      SCI in rats. Therefore, treatment with ML228 may be developed as a novel
      therapeutic strategy to treat SCI.

PMID- 28450911
TI  - Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root
      ganglion neurons.
AB  - The renin-angiotensin system (RAS) is involved in nociception and has functions
      in the cardiovascular system. The primary role of the RAS is to mediate the
      effect of angiotensin II (Ang II) through Ang II receptor type 2 (AT2). Due to
      this, AT2 has become a novel therapeutic target for the relief of peripheral
      neuropathic pain in humans. As it is one of the most popular induction agents of
      general anesthesia, propofol also exerts peripheral antinociceptive effects. The
      present study assessed the effect of propofol on the expression of AT2 in
      cultured dorsal root ganglion (DRG) neurons. The results indicate that propofol
      decreases AT2 mRNA expression in a statistically significant dose- and time
      dependent manner (P<0.05). This resulted in a marked decrease in AT2 protein
      expression and the density of Ang II-binding AT2 on the cell membrane of DRG
      neurons. The effect of propofol was reversed by LY294002, a phosphatidylinositol
      3-kinase (PI3K) inhibitor. Although propofol exhibited no significant effect on
      AT2 gene promoter activity, it significantly decreased the stability of AT2 mRNA
      (P<0.05). However, this effect was reversed by LY294002. In addition, propofol
      increased PI3K activity in a concentration-dependent manner in DRG neurons. In
      conclusion, to the best of our knowledge, the current study provides the first
      evidence suggesting that propofol inhibits the expression of AT2 in DRG neurons
      by decreasing the stability of AT2 mRNA through a PI3K-dependent mechanism. The
      present study provides novel insights into the mechanisms of the peripheral
      antinociceptive action of propofol and suggests a potential means of regulating
      Ang II/AT2 signaling in the peripheral nervous system.

PMID- 28450912
TI  - Effects of the modified electric convulsive treatment (MECT) on cell factors of
      schizophrenia.
AB  - The expression of cell factors of schizophrenia and the effect of the modified
      electric convulsive treatment (MECT) were studied. In total, 156 patients with
      schizophrenia were selected, and divided into the drug group (70 cases) and the
      drug combined with MECT group (combined group) (86 cases) according to the
      treatment methods. In addition, 70 cases of healthy volunteers (control group)
      were selected according to the closest matching method based on 1:1 of age and
      gender. The drug treatment, consisted of anti-psychotic drugs, such as
      risperidone 2-8, quetiapine 300-750, ziprasidone 80-160 or aripiprazole 10-30
      mg/day, and for the control group, we used the electric spasm therapeutic
      instrument, Thymatron(r)IV Systems up to 6 times, 3 times a week. The levels of
      interleukin (IL)-10, IL-4, IL-6 and IL-1 were detected before and after treatment
      by ELISA. The positive and negative symptom scale (PANSS) was used to evaluate
      the efficiency. Before the treatment, IL-1 and IL-6 levels of drug and combined
      groups were significantly higher than those of the control group (P<0.05), while
      IL-4 and IL-10 had no difference with the control group. There was no significant
      difference of each factor between the drug and combined groups. After treatment,
      IL-1, IL-6 and IL-10 of the drug group did not change compared to the levels
      before treatment, but IL-4 increased significantly; IL-1 and IL-10 of the
      combined group did not change, while IL-4 and IL-6 increased significantly; IL-1,
      IL-4 and IL-6 of the drug and combined groups were significantly (P<0.05) higher
      than those in the control group, but not IL-10. IL-1, IL-4 and IL-6 levels of the
      combined group were significantly higher (P<0.05) than those of the drug group.
      After treatment, the PANSS scores of the two groups decreased and the combined
      group decreased more significantly (P<0.05). The reduction rate of the combined
      group was significantly higher (P<0.05) than that of the drug group. The total
      efficiency of the combined group was significantly higher than that of the drug
      group, and after comparing these levels, there was statistical significance
      (P<0.05). IL-1, IL-4, IL-6 and IL-10 levels of the drug and combined groups
      before treatment were not associated with PANSS scores and the variation of IL-1,
      IL-4, IL-6 and IL-10 of the drug and combined groups had no correlation with the
      reduction rate of the PANSS. The results showed that, cell factors of
      schizophrenia had an abnormal expression, and medication and MECT can affect the
      expression level. In addition, MECT can improve the effect in the treatment of
      schizophrenia, but had no obvious correlation with the change of cell factors.

PMID- 28450913
TI  - Orally administered simvastatin partially preserves lumbar vertebral bone mass
      but not integrity of intervertebral discs in ovariectomized rats.
AB  - The present study aimed to investigate the effect of orally administered
      simvastatin on lumbar vertebral bone mass and intervertebral disc (IVD)
      degeneration in ovariectomized (OVX) rats. A total of 30 female Sprague-Dawley
      (SD) rats were subjected to either bilateral ovariectomy (n=20) or sham surgery
      (n=10). After 12 weeks, the OVX rats were orally administered either saline
      vehicle (OVX + V group; n=10), or 5 mg/kg/day simvastatin (OVX + SIM group;
      n=10). Following 12 weeks of treatment, necropsy was conducted and bone mineral
      density (BMD) was determined in the L5-6 vertebrae. Furthermore, the
      microstructure and biomechanical properties of the L3 vertebrae were detected by
      micro-computed tomography and compression testing, respectively. The L5-6
      vertebrae were analyzed by measurement of IVD height, observation of histological
      changes by van Gieson staining, and evaluation of collagen-II (col-II), aggrecan
      (AGG) and collagen I (col-I) expression by immunohistochemical analysis. Rats in
      the OVX+V group had lower BMD, bone volume/trabecular volume ratio, maximum load
      and elastic modulus than the sham group. Rats in the OVX + SIM group had higher
      BMD and biomechanical strength values than the rats in the OVX+V group.
      Histological analysis showed that the OVX + V and OVX + SIM groups exhibited
      significantly higher disc degeneration scores and significantly lower IVD height
      than the sham group. Immunohistochemical analysis revealed lower expression
      levels of col-II and AGG, but higher levels of col-I in the annulus fibrosis and
      endplate in OVX+V rats compared with the sham group. The OVX + SIM group
      exhibited levels of col-II, AGG and col-I expression comparable with those of
      OVX+V rats, with the exception of an upregulation of col-II expression in the
      annulus fibrosis. These data demonstrate that simvastatin treatment partially
      prevented bone loss and the deterioration of biomechanical properties of lumbar
      vertebrae, but not the progression of IVD degeneration in OVX rats.

PMID- 28450914
TI  - Syringe needle skull penetration reduces brain injuries and secondary
      inflammation following intracerebral neural stem cell transplantation.
AB  - Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering
      stem cell grafts effectively, however, this approach may subsequently result in
      brain injury and secondary inflammation. To reduce the risk of promoting brain
      injury and secondary inflammation, two methods were compared in the present
      study. Murine skulls were penetrated using a drill on the left side and a syringe
      needle on the right. Mice were randomly divided into three groups (n=84/group):
      Group A, receiving NSCs in the left hemisphere and PBS in the right; group B,
      receiving NSCs in the right hemisphere and PBS in the left; and group C,
      receiving equal NSCs in both hemispheres. Murine brains were stained for
      morphological analysis and subsequent evaluation of infiltrated immune cells.
      ELISA was performed to detect neurotrophic and immunomodulatory factors in the
      brain. The findings indicated that brain injury and secondary inflammation in the
      left hemisphere were more severe than those in the right hemisphere, following
      NSC transplantation. In contrast to the left hemisphere, more neurotrophic
      factors but less pro-inflammatory cytokines were detected in the right
      hemisphere. In addition, increased levels of neurotrophic factors and interleukin
      (IL)-10 were observed in the NSC transplantation side when compared with the PBS
      treated hemispheres, although lower levels of IL-6 and tumor necrosis factor
      alpha were detected. In conclusion, the present study indicated that syringe
      needle skull penetration vs. drill penetration is an improved method that reduces
      the risk of brain injury and secondary inflammation following intracerebral NSC
      transplantation. Furthermore, NSCs have the potential to modulate inflammation
      secondary to brain injuries.

PMID- 28450915
TI  - Emulsified isoflurane combined with therapeutic hypothermia improves survival and
      neurological outcomes in a rat model of cardiac arrest.
AB  - Emulsified isoflurane (EIso), when introduced following cardiopulmonary
      resuscitation (CPR), significantly improves survival and neurological outcomes in
      a rat model of cardiac arrest (CA). The present study aimed to examine whether
      EIso combined with therapeutic hypothermia (TH) confers an additive
      neuroprotective effect. Adult male Sprague-Dawley rats that were subjected to
      return of spontaneous circulation (ROSC) after a 6-min asphyxia-induced CA were
      randomized to five groups: Sham group, control group under normothermic
      conditions, EIso group (4 ml/kg for 30 min under normothermic conditions), TH
      group (33 degrees C for 2 h), and EIso plus TH group. Survival conditions and
      neurological outcomes were evaluated at 1 day and 7 days after ROSC. Animal
      survival rate at 7 days after ROSC was 30.7% in the CPR group, 60% in the EIso
      group, 63.6% in the TH group and 72.7% in the EIso plus TH group. EIso, TH and
      EIso plus TH yielded significant improvements in survival rates, neural deficit
      score and cognitive function, and ameliorated hippocampal CA1 region cell injury
      and apoptosis at 1 day and 7 days after ROSC compared with the CPR group.
      Combined therapy of EIso and TH was superior to EIso or TH alone, suggesting that
      combined EIso and TH treatment results in significant improvements in survival
      and neurological outcomes, and was more effective than independent EIso or TH
      treatment.

PMID- 28450917
TI  - Diagnostic value of high-frequency color Doppler ultrasonography examination in
      combination with anti-cyclic citrullinated peptide antibody testing in rheumatoid
      arthritis patients.
AB  - We studied the diagnostic value of high-frequency color Doppler ultrasonography
      (HCDU) examination in combination with anti-cyclic citrullinated peptide (anti
      CCP) antibody testing in rheumatoid arthritis (RA) patients with finger joint
      damage. From January 2015 to December 2015, 80 patients diagnosed with RA with
      finger joints damage were enrolled in this study. Patients were examined with
      HCDU. Serum anti-CCP antibody level was tested using ELISA, and results were
      compared with the healthy control group. Results obtained by ELISA demonstrated
      that the positive rate of anti-CCP antibodies was 73.8% in the study group, and
      10% in the control group. The negative rate was 26.2% in the study group, and 90%
      in the control group. HCDU examination suggested that the predominantly affected
      joint by bone erosion of RA with finger joint damage was MCP3 (16.7%), followed
      by PIP3 (14.1%), MCP2 (13.5%) and PIP2 (12.8%). The slightest affected joint was
      thumb metacarpophalangeal joint, followed by thumb, little finger
      metacarpophalangeal joint and proximal interphalangeal joint. The sensitivity of
      diagnosis of RA with finger joints damage with both HCDU and CCP antibody
      examination showed a significantly lower level compared with examination with
      each one of the methods alone, while specificity showed a significantly higher
      level. Thus, a combination of HCDU examination and anti-CCP antibody testing can
      be considered useful to improve the early diagnostic rate of RA. HCDU examination
      is a sensitive, secure, atraumatic and easily-operated diagnostic method for
      early RA patients with finger joint damage. When combined with anti-CCP antibody
      testing, it will provide a better chance for RA patients, and give them hope for
      a better treatment and improved prognosis.

PMID- 28450916
TI  - Exercise training on chronotropic response and exercise capacity in patients with
      type 2 diabetes mellitus.
AB  - The study was designed to observe the effects and relationship of exercise on
      chronotropic response (CR) and exercise capacity in patients with type 2 diabetes
      mellitus (T2DM). A total of 30 patients with T2DM underwent symptom-limited
      cardiopulmonary exercise testing (CPET) after excluding contraindication. For
      each subject individualized exercise prescription was formulated, and they
      received 12 weeks of exercise training after CPET retest to complete the
      comparison of CR indicators, including the ratio of maximum exercise heart rate
      to predicted maximum heart rate value (rHR), heart rate reserve rate (HRRes),
      heart rate recovery (HRR) of 1-6 min after exercise termination (HRR1-6),
      exercise capacity (peak VO2/kg) and other indicators. The results showed that
      after 12 weeks of exercise treatment, rHR, HRRes, HRR1-6, and peak VO2/kg were
      significantly higher than before (P<0.05), with peak VO2/kg being positively
      correlated to rHR and HRRes (P<0.01). In conclusion, exercise training can
      improve cardiac dysfunction, abnormal HRR, enhance exercise capacity and
      adaptability of the cardiovascular system to exercise stress in T2DM patients.

PMID- 28450918
TI  - Association between the extent of white matter damage and early cognitive
      impairment following acute ischemic stroke.
AB  - White matter (WM) injury following acute ischemic stroke (AIS) is associated with
      cognitive decline. Establishing relationships between the specific cognitive
      tests used to assess post-AIS cognition and various clinical indices of WM injury
      severity and distribution may aid in prognosis and early treatment decisions. We
      enrolled 62 patients with AIS to Weifang People's Hospital between September 2014
      and August 2015. WM lesion severity and distribution were examined by computed
      tomography (CT) and magnetic resonance imaging (MRI). The Blennow scale was used
      for scoring the distribution and degree of WM lesions (WMLs) on CT images, the
      Fazekas scale for scoring periventricular and deep WMLs on MRI, and the
      Cholinergic Pathways Hyperintensities Scale (CHIPS) for scoring MRI manifestation
      of cholinergic fiber damage. The 8-domain Montreal Cognitive Assessment (MoCA)
      was used to evaluate cognitive function. Mean +/- standard deviation scores on
      the Blennow scale was 1.6+/-0.5; Fazekas scale, 3.4+/-0.8; and CHIPS, 65.7+/
      12.5. The proportion of patients with a MoCA score <26 (indicating cognitive
      dysfunction) was significantly higher in subgroups with Blennow scale score >2,
      Fazekas scale score >4, and CHIPS score >51 (all P<0.001). The MoCA score was
      negatively correlated with Blennow scale score (r=-0.326, P=0.002), Fazekas scale
      score (r=-0.404, P=0.031), and CHIPS score (r=-0.234, P=0.042). Thus, the degree
      and distribution of whole-brain, deep, and cholinergic WMLs were associated with
      cognitive impairment. The Blennow scale, Fazekas scale, and CHIPS all provide
      good predictive efficacy of post-AIS cognitive dysfunction.

PMID- 28450919
TI  - Areas of breast tissue covered in cone beam breast CT imaging.
AB  - The value of cone beam breast computed tomography (CBBCT) imaging on covered
      areas of breast tissue, which is the relation between imaging quality and CT dose
      were studied. Multi-energy spectrum was used to radiate same-size built-in
      calcifications and lump breast motifs under the condition of the same number of
      particles by utilizing the Monte Carlo-based GATE simulation software; breast
      motif images were restructured by using FBP restructuration algorithm to gain the
      distribution of radiation dose in the breast motif; radiation dose was calculated
      and signal-to-noise ratio (SNR) to define how quality factor M and dose
      efficiency eta reflect the relations between radiation dose and imaging quality.
      Based on the comparison of the calcification number, diameter, and the diameter
      of tumor among head side, foot side, inner side, outer side and rear side, the
      difference was meaningless in terms of statistics. Based on the comparison
      between SNR and contrast-to-noise ratio and between dose efficiency eta and
      quality factor M in different areas, the difference was not statistically
      significant. In conclusion, the imaging quality of CBBCT was good in the head,
      foot, inner, outer and rear sides of breast, with acceptable CT dose.

PMID- 28450920
TI  - Detection and analysis of hepatitis C virus in HIV-infected patients in the
      Guangxi province of China.
AB  - The aim of the present study was to investigate the prevalence rate of hepatitis
      C virus (HCV) infection in human immunodeficiency virus (HIV)-positive
      individuals and to study the infection status of HCV RNA in HIV-infected
      individuals who did not have anti-HCV antibodies in the Guangxi province of
      China, in order to provide basis for screening and clinical treatment of
      hepatitis C in future. Data were collected from patients recruited via a
      questionnaire. Between August 2008 and January 2009, 300 HIV-infected individuals
      were randomly selected from various HIV monitoring points in Liuzhou and Qinzhou
      (Guangxi, China). In addition, 41 patients with only hepatitis C were recruited
      from a hospital clinic (First Affiliated Hospital of Guangxi Medical University,
      Nanning, China). HCV antibodies in patient serum samples were detected by ELISA.
      HCV RNA expression was detected using nested polymerase chain reaction (PCR), HCV
      RNA levels in the serum were evaluated using quantitative fluorescence PCR, and
      HCV genotypes were confirmed using restriction fragment length polymorphism. The
      infection rate of HCV in the HIV-infected people was 48.67%. The anti-HCV
      positive rate differed between routes of disease transmission: Anti-HCV positive
      rate was 63.7% among drug users, 34.96% among sex-transmitted persons and 1.37%
      among other persons. In the anti-HCV-negative group, the HCV RNA-positive rate
      was 26.62%. In the anti-HCV-positive group, HCV RNA positive rate was 78.08%. HCV
      RNA level of HIV/HCV coinfected patients was higher than those infected with HCV
      alone, and there was no difference of anti-HCV-positive rate among different
      levels of HCV RNA. HCV genotypes of HIV/HCV coinfected persons showed diversity
      across Guangxi, and the predominant ones were the 1b and mixed subtypes. The
      predominant HCV genotypes were 6a, mixed subtypes and 3b amongst patients that
      contracted HCV via drug use-related routes of transmission. The patients with HCV
      transmission routes other than drug-related routes possessed 1b and 1a+1b
      genotypes. In conclusion, there was a large proportion of HIV infected persons
      with mixed HCV infection in the Guangxi province of China. The present results
      show that 26.62% of HCV-infected persons will be fail to be diagnosed with
      hepatitis C virus coinfection if we simply use ELISA to detect HCV antibody. The
      predominant HCV genotypes were 1b, mixed, 6a and 3b in HIV/HCV coinfected
      persons.

PMID- 28450921
TI  - Research on the effect of ginseng polysaccharide on apoptosis and cell cycle of
      human leukemia cell line K562 and its molecular mechanisms.
AB  - Ginseng polysaccharide (GPS), a polymer of glucose and the primary constituent
      extracted from panax ginseng, has been documented to exert various
      pharmacological properties, including anti-tumor properties. To provide further
      insights into the anti-tumor functions of GPS, the present study was designed to
      investigate the effect of GPS on apoptosis and the cell cycle of human leukemia
      cell line K562 cells, and its underlying mechanisms. The results demonstrated
      that GPS could inhibit K562 cell proliferation and induce apoptosis in vitro in a
      concentration- and time-dependent manner. The transcription of P38 and c-Jun NH2
      terminal kinase (JNK) mRNA were significantly augmented, while the transcription
      of extracellular signal-regulated kinase (ERK) mRNA were significantly reduced
      following treatment with GPS compared with the control group (all P<0.05). In
      addition, GPS treatment markedly suppressed the expression of phosphorylated (p)
      ERK, nuclear factor (NF)-kappaB p65 and cyclin D1, and increased the synthesis of
      p-P38 and p-JNK protein expression, as evidenced by immunofluorescence and
      western blotting analyses. In conclusion, the results indicate that the GPS
      mediated MAPK/NF-kappaB/cyclin D1 signaling pathway serves a crucial role in cell
      cycle arrest and apoptosis of K562 cells.

PMID- 28450922
TI  - MicroRNA-17-5p mediates hypoxia-induced autophagy and inhibits apoptosis by
      targeting signal transducer and activator of transcription 3 in vascular smooth
      muscle cells.
AB  - The aim of the present study was to investigate hypoxia-induced apoptosis and
      autophagy in vascular smooth muscle cells (VSMCs) and the underlying molecular
      mechanisms of microRNA (miR)-17-5p responses in an anaerobic environment. The
      results revealed that miR-17-5p expression was significantly upregulated in VSMCs
      subjected to hypoxic conditions (P<0.05) and lower miR-17-5p levels were observed
      in ethyl 3,4-dihydroxybenzoate-treated and hypoxia inducible factor-1 loss-of
      function cells. Additionally, it was demonstrated that miR-17-5p is associated
      with hypoxia-induced autophagy, which was confirmed by upregulating the light
      chain 3-II/LC3-I ratio and downregulating nucleoporin p62. Cell apoptosis was
      inhibited in response to hypoxia, and levels of pro-apoptotic proteins B-cell
      lymphoma 2-associated X protein and p-caspase were markedly decreased when VSMCs
      were subjected to hypoxic conditions. Furthermore, expression of signal
      transducer and activator of transcription 3 (STAT3) decreased when cells were
      transfected with overexpressing miR-17-5p and subjected to hypoxic conditions,
      and the combination of miR-17-5p loss-of-function and hypoxia induced greater
      upregulation in the protein expression of STAT3 compared with a single treatment
      for hypoxia in VSMCs. In conclusion, miR-17-5p may be a novel hypoxia-responsive
      miR and hypoxia may induce protective autophagy and anti-apoptosis in VSMCs by
      targeting STAT3.

PMID- 28450923
TI  - Expression and roles of TIPE2 in autoimmune hepatitis.
AB  - Tumor necrosis factor, alpha-induced protein 8-like 2 (TIPE2) is associated with
      the development of hepatic inflammatory diseases. However, to date, the possible
      role of TIPE2 in autoimmune hepatitis (AIH) has not been reported. The present
      study aimed to investigate the expression of TIPE2 in peripheral blood
      mononuclear cells (PBMCs) of mice with AIH. Furthermore, the liver function, pro
      inflammatory cytokine production and hepatic histopathology were examined in
      TIPE2-deficient mice in order to evaluate whether TIPE2 is involved in the
      pathogenesis of AIH. A murine model of AIH was induced by treatment with
      concanavalin A (ConA). The expression of TIPE family members in the PBMCs was
      examined using reverse-transcription quantitative polymerase chain reaction
      analysis, while the protein expression of TIPE2 was additionally detected by
      western blot analysis. The activity of alanine amiotransferase (ALT) and
      aspartate aminotransferase (AST) in the serum was measured on an automated
      chemical analyzer to assess liver function. The serum levels of tumor necrosis
      factor-alpha, interleukin (IL)-6 and IL-12 were measured using commercial ELISA
      kits. Hematoxylin and eosin staining was performed to assess hepatic
      histopathology. The results showed that the expression of TIPE2 was significantly
      decreased in the mice with AIH. Following ConA-induced AIH, TIPE2-deficient mice
      had significantly increased serum ALT and AST levels, enhanced production of pro
      inflammatory cytokines, as well as more severe hepatic inflammation compared with
      the wild-type mice. In conclusion, the present study demonstrated, for the first
      time, that TIPE2 is involved in the pathogenesis of AIH. TIPE2 prevents liver
      dysfunction and inhibits deleterious inflammatory immune responses after AIH and
      may therefore serve as a novel agent for the treatment of AIH.

PMID- 28450924
TI  - Significance of combined detection of JAK2V617F, MPL and CALR gene mutations in
      patients with essential thrombocythemia.
AB  - The aim of this study was to analyze the mutation rate of JAK2V617F, MPLW515L/K
      and CALR genes in adult patients with essential thrombocythemia (ET) and the
      accuracy of the combined detection by the receiver operating curve. Three hundred
      and forty-two cases with high-platelets (>=300*109/l) were consecutively
      selected. The patients were analyzed for routine blood examination, bone marrow
      biopsy and genetic testing. One hundred and fifty-four cases (45.03%) were
      diagnosed with ET and 188 cases of secondary thrombocythemia according to the
      hematopoietic and lymphoid tissue tumor classification standards of 2008. It was
      found that the mutant type of three genes showed three bands, whereas only one
      band for wild-type. The JAK2V617F and MPL mutations did not cause a change in the
      open reading frame and the CALR mutation resulted in its change. The mutation
      rate of JAK2V617F and CALR in ET group was significantly higher than that in the
      secondary thrombocythemia group (p<0.05). The positive mutation rate of MPL was
      only 4.55%. JAK2V617F-positive mutation alone was used to diagnose with ET. The
      area under the curve (AUC) was 0.721. The sensitivity was 72.4%, the specificity
      was 79.5% and the cut-off value was 0.25. When CALR-positive mutation alone was
      used to diagnose ET, the AUC, sensitivity, specificity and cut-off value were
      0.664, 68.4, 82.4 and 0.09%, respectively. JAK2V617F combined with CALR mutation
      were used for diagnosis of ET. The AUC was 0.862, the sensitivity was 85.9%, the
      specificity was 87.8%, and the cut-off values were 0.21 and 0.07. In conclusion,
      the positive mutation rate of JAK2V617F and CALR in ET was higher, and the
      sensitivity, specificity and accuracy of the diagnosis of ET were significantly
      improved using the detection of JAK2V617F and CALR.

PMID- 28450926
TI  - Effects of weight training time on bone mineral density of patients with
      secondary osteoporosis after hemiplegia.
AB  - The aim of the study was to investigate the effects of weight training time on
      bone mineral density (BMD) of patients with secondary osteoporosis after
      hemiplegia. A total of 129 hemiplegic patients with stroke, 75 males and 54
      females, aged 50-75 years, were recruited in this study. Male patients were
      randomly divided into 3 groups (25 cases each) receiving 30 min (group M30), 60
      min (group M60), or 90 min (group M90) daily upright bed weight training. Female
      patients were similarly randomly allocated into groups F30, F60 and F90 (18 cases
      each) with daily upright bed weight training for 30, 60 and 90 min, respectively.
      After 3 months of training, BMD at anteroposterior lumbar spine (L1-L4) and
      ipsilateral femoral neck were examined by dual-energy X-ray absorptiometry.
      Compared to pre-treatment, no statistical difference in BMD was found after 3
      months in males who underwent daily 30-min weight training (group M30). By
      contrast, a significant increase in BMD was seen at lumbar and femoral neck in
      groups M60 and M90 after 3 months (all p<0.05). By pair-wise comparison, we found
      that BMD at lumbar and at femoral neck was significantly higher in groups M60 vs.
      M30 and in groups M90 vs. M60 (all p<0.05). For female subjects, daily 90-min
      weight training significantly increased BMD at lumbar and at femoral neck in
      group F90 (both p<0.05), but daily 30- or 60-min weight training did not produce
      similar improvement after 3 months. By pair-wise comparison, we found a
      significantly higher BMD at lumbar and at femoral neck in groups F90 vs. F60
      after 3 months of treatment (both p<0.05). In conclusion, in order to stimulate
      BMD and reverse osteoporosis in patients with secondary osteoporosis after
      hemiplegia, daily weight training for minimum 60 and 90 min was needed for males
      and females, respectively.

PMID- 28450925
TI  - Therapeutic effect of apocynin through antioxidant activity and suppression of
      apoptosis and inflammation after spinal cord injury.
AB  - Spinal cord injury (SCI) is a devastating condition affecting hundreds of
      thousands of people worldwide annually. SCI results in activation of the
      inflammatory response and apoptosis, and generates oxidative stress, which has
      deleterious effects on the recovery of motor function. Apocynin, an inhibitor of
      NADPH oxidase, has been demonstrated to improve neuronal functional recovery in
      rat models of SCI. However, the efficacy of apocynin treatment post-SCI has not
      been investigated. The aim of this study was to observe the effects of apocynin
      on the repair of acute spinal cord damage in rats and to examine the potential
      beneficial effects. A rat model of SCI was established, and apocynin (50 mg/kg)
      was administered intraperitoneally at 30 min after SCI and then every 12 h for 3
      days. In order to examine oxidative tissue injury, the levels of malondialdehyde
      and glutathione and activities of myeloperoxidase and superoxide dismutase in the
      spinal cord tissues were measured. Histological evaluations were also conducted.
      NeuN labeling, TUNEL staining and caspase 3 immunohistochemical staining were
      performed to analyze neuronal damage and apoptosis around the lesion.
      Immunohistochemical analysis was also carried out to observe the expression of
      CD11b and glial fibrillary acidic protein. The expression levels of bax, bcl-2,
      tumor necrosis-alpha, interleukin (IL)-1beta and IL-6 in the spinal cord tissue
      were assayed by western blotting. Finally, locomotor function was evaluated using
      the inclined plane test and Basso, Beattie and Bresnahan scores. The results
      showed that treatment with apocynin decreased oxidative damage, alleviated
      neuronal apoptosis, inhibited the inflammatory response and resulted in the
      promotion of locomotor function. Therefore, this study confirmed the therapeutic
      efficacy of apocynin in the repair of SCI, which was probably mediated via the
      inhibition of apoptosis and the inflammatory response, thus promoting the
      restoration of nerve function.

PMID- 28450927
TI  - Application of 3D-HyCoSy in the diagnosis of oviduct obstruction.
AB  - The aim of the study was to analyze the application value of three-dimensional
      hysterosalpingo-contrast sonography (3D-HyCoSy) in the diagnosis of oviduct
      obstruction. Fifty-two patients with infertility and oviduct obstruction were
      continuously selected and treated with 3D-HyCoSy and CLP (CLP). It was found that
      according to CLP diagnosis, 40 oviducts were obstructed, 30 were partially
      obstructed, 12 were tortuous and 22 were completely obstructed. The 40 cases were
      unilaterally pathological, 24 were bilaterally pathological, 10 were diagnosed as
      congenital dysplasia, 35 were diagnosed as inflammation and 19 were diagnosed as
      tumor and cyst. Based on the diagnostic criteria of CLP, the diagnostic
      sensitivity, specificity, positive predictive values and negative predictive
      values of 3D-HyCoSy was 82.4, 88.3, 77.9 and 90.2%, respectively. The contrast
      agent flow time of oviduct obstruction (tortuosity and complete obstruction) as
      diagnosed by 3D-HyCoSy was significantly prolonged when compared with that of
      partial oviduct obstruction (P<0.05), and flow time of inflammation as diagnosed
      thereby was longer than that of congenital dysplasia, tumor and cyst. Following
      the diagnosis of inflammation, the shape of the contrast agent was tenuous,
      swollen, angled, rigid and distorted and the occurrence rate of inflammation was
      significantly higher (P<0.05). In conclusion, the diagnostic effect of 3D-HyCoSy
      on oviduct obstruction was more accurate and can show different features when
      diagnosing different types of inflammation, thus having a certain value for
      identifying the inflammation.

PMID- 28450928
TI  - Effect of etomidate on the oxidative stress response and levels of inflammatory
      factors from ischemia-reperfusion injury after tibial fracture surgery.
AB  - The effect of etomidate on the oxidative stress response and levels of
      inflammatory factors resulting from ischemia-reperfusion injury of the lower
      extremities during tibial fracture surgery were investigated. From December 2013
      to June 2015, 60 tibial fracture patients with surgical indications for open
      reduction and internal fixation were selected. Patients were randomly divided
      into the observation group and the control group. All patients were stanched by
      tourniquet hemostasis. Patients in the observation group were anesthetized with
      etomidate (3-6 mg/kg.h) + remifentanil (0.1-0.25 ug/kg/min) administered with an
      injection pump to maintain intraoperative sedation and analgesia anesthesia.
      Patients in the control group received propofol (3-6 mg/kg.h) + remifentanil (0.1
      0.25 ug/kg/min). Before surgery (T0), before surgery was completed and anesthesia
      was stopped (T1), 24 h after surgery (T3), 48 h after surgery (T4), and 1 week
      after surgery (T5), serum superoxide dismutase (SOD) activity was determined with
      a kit, and ELISA was used to measure the levels of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1, and IL-6 in peripheral blood from both groups of
      patients. Surgery in both groups was completed smoothly. We found that serum SOD
      levels of patients in the observation group were significantly higher than those
      of the control group, while the levels of TNF-alpha, IL-1, and IL-6 released by
      neutrophils were significantly decreased after ischemia-reperfusion injury
      (P<0.05). Postoperative length of stay in hospital of the observation group was
      significantly shorter and the occurrence rate of anesthesia complications was
      significantly lower than in the control group (P<0.05). In conclusion, during
      surgery for lower limb fracture, the use of etomidate for maintaining sedation
      can effectively maintain serum SOD activity and inhibit the release of
      inflammatory factors after ischemia-reperfusion injury of the fracture, to reduce
      the occurrence rate of anesthesia complications after surgery.

PMID- 28450930
TI  - Epidemiological analysis of 9,596 patients with acute lung injury at Chinese
      Military Hospitals.
AB  - Acute lung injury (ALI) is a common and severe disease that has been associated
      with significant morbidity and mortality. Understanding the epidemiology of ALI
      is vital for its prevention and treatment. The present study aimed to analyze the
      epidemiology of ALI by collecting data from patients that were submitted between
      2000 and 2008 into the 'No. 1 Military Medical Project' information system. A
      total of 9,596 ALI patients were analyzed retrospectively, including 7,284 males
      (75.91%) and 2,312 females (24.09%). The median age of the patients was 44 years
      (interquartile range, 31-63 years), and there was a significant difference
      between the median ages of male and female patients (P<0.01). The number of
      patients with ALI admitted to the hospitals showed an increasing trend over time.
      However, there was no significant difference in the annual gender distribution
      (P>0.05). In addition, ALI was more prevalent in May, July, August, October,
      November and December, as compared with the other months. ALI occurred at any
      age, although 40-years-old was the peak age. There was a significant difference
      in the age group distributions of male and female ALI patients (P<0.01). Among
      the predisposing conditions, pulmonary contusion represented the highest
      proportion (45.71%), followed by pneumonia or respiratory tract infection
      (23.68%) and pulmonary malignant tumor (6.30%). Of the 581 (6.05%) mortalities,
      pneumonia was the most common cause (37.87%), followed by malignancies (16.87%)
      and pulmonary embolism (11.02%). However, the highest mortality rate was
      associated with cardiopulmonary resuscitation (48.28%). In conclusion, the
      results of the present study suggested that ALI should be increasingly monitored
      in the future, and predisposing conditions should be regarded as one of the most
      important features determining the management of ALI.

PMID- 28450929
TI  - Effect of intranasal stem cell administration on the nigrostriatal system in a
      mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease
      worldwide. It affects the locomotor system, leading to a final severe disability
      through degeneration of dopaminergic neurons. Despite several therapeutic
      approaches used, no treatment has been proven to be effective; however, cell
      therapy may be a promising therapeutic method. In addition, the use of the
      intranasal (IN) route has been advocated for delivering various therapies to the
      brain. In the present study, the IN route was used for administration of
      mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN
      delivery as an alternative route for cell based therapy administration in PD. The
      PD model was developed in C57BL/6 mice using intraperitoneal rotenone
      administration for 60 consecutive days. MSCs were isolated from the mononuclear
      cell fraction of pooled bone marrow from C57BL/6 mice and incubated with
      micrometer-sized iron oxide (MPIO) particles. For IN administration, we used a 20
      ul of 5*105 cell suspension. Neurobehavioral assessment of the mice was
      performed, and after sacrifice, brain sections were stained with Prussian blue to
      detect the MPIO-labeled MSCs. In addition, immunohistochemical evaluation was
      conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum
      and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The
      neurobehavioral assessment revealed progressive deterioration in the locomotor
      functions of the rotenone group, which was improved following MSC administration.
      Histopathological evaluation of brain sections in the rotenone+MSC group revealed
      successful delivery of MSCs, evidenced by positive Prussian blue staining.
      Furthermore, rotenone treatment led to significant decrease in dopaminergic
      neuron number in SNpc, as well as similar decrease in the corpus striatum fiber
      density. By contrast, in animals receiving IN administration of MSCs, the
      degeneration caused by rotenone treatment was significantly counteracted. In
      conclusion, the present study validated that IN delivery of MSCs may be a
      potential safe, easy and cheap alternative route for stem cell treatment in
      neurodegenerative disorders.

PMID- 28450931
TI  - Cell penetrating peptide of sodium-iodide symporter effect on the I-131
      radiotherapy on thyroid cancer.
AB  - The aim of the present study was to clarify whether the cell penetrating peptide
      of sodium-iodide symporter (NIS) has an effect on the I-131 radiotherapy of
      thyroid cancer. Firstly, we combined the HIV-1 TAT peptide (a cell penetrating
      peptide, dTAT) and established a nanoparticle vector (dTAT NP) to study the
      delivery efficiency of this cell-penetrating strategy for tumor-targeted gene
      delivery. dTAT NP was transfected into cultured TPC-1 cells as a model to study
      the effects of I-131 radiotherapy on thyroid cancer. Reverse transcription
      quantitative polymerase chain reaction and western blotting results showed that
      the mRNA and protein expression levels of NIS in the transfected TPC-1 cells were
      substantially higher than in the negative control cells. MTT and flow cytometric
      analyses demonstrated that the cell growth and apoptosis rates of the TPC-1 cells
      were significantly inhibited and activated, respectively, by treatment with dTAT
      NP. The results of DAPI staining showed that treatment with dTAT NP visibly
      increased the nuclear apoptosis rate of the TPC-1 cells. The effect of dTAT NP on
      TPC-1 cells was associated with the promotion of caspase-3 and downregulation of
      the PI3K/Akt signaling pathway. In summary, the present data provide a pre
      clinical proof-of-concept for a novel gene delivery system that efficiently
      delivers NIS to the targeted cancer cells and presents a satisfactory efficacy.
      This approach may offer an effective strategy for improving thyroid cancer gene
      therapy.

PMID- 28450932
TI  - Echocardiographic characterization of hypertrophic cardiomyopathy in Chinese
      patients with myosin-binding protein C3 mutations.
AB  - Hypertrophic cardiomyopathy (HCM) is a common autosomal dominant cardiac disease,
      affecting 1 in 500 people. Myosin-binding protein C3 (MyBPC3) gene mutations are
      the most common genetic cause of HCM. However, the prevalence of the MyBPC3 gene
      mutation in Chinese patients with HCM, and their echocardiographic
      characteristics, remain unknown. In the present study, 48 Chinese patients with
      HCM were sequenced to identify the MyBPC3 gene and were characterized by their
      clinical features using 2-dimensional echocardiography and real-time 3
      dimensional echocardiography. Nine MyBPC3 mutations were identified in seven
      unrelated patients out of 48 cases, which accounts for a 15% prevalence of MyBPC3
      mutations in Chinese patients with HCM. Family members of the seven patients were
      further tested and divided into the following two groups based on HCM phenotype
      and MyBPC3 mutations: Positive genotype with left ventricular (LV) hypertrophy
      (LVH) (G+/LVH+, n=18); and positive genotype without LVH (G+/LVH-, n=23). These
      groups were compared with matched normal control subjects (n=30). G+/LVH+
      patients showed significantly lower septal and lateral Tissue Doppler imaging
      (TDI)-derived systolic, early and late diastolic mitral annular velocities
      compared with the controls. In addition, diastolic dyssynchrony index (DDI) was
      markedly higher in the G+/LVH+ subjects. However, only septal Ea was
      significantly lower in G+/LVH- subjects in comparison with controls, with no
      significant difference in lateral Sa, Ea and Aa, and DDI. In conclusion, the
      patients in the present study demonstrated a 15% prevalence of MyBPC3 gene
      mutations in the Chinese HCM population. MyBPC3 gene mutations may cause regional
      LV hypertrophic remodeling first and further proceed to global hypertrophic
      remodeling and myocardial diastolic dysfunction.

PMID- 28450933
TI  - Retrospective analysis of fosfomycin combinational therapy for sepsis caused by
      carbapenem-resistant Klebsiella pneumoniae.
AB  - The aim of the present study was to compare the efficacy and safety of fosfomycin
      combinational therapy with other antibiotics for the treatment of infections
      caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This retrospective
      cohort study examined 104 cases of sepsis caused by CRKP occurring between
      January 2012 and November 2014 in Shanghai Tenth People's Hospital. Three
      categories of patient outcome were assessed: Survival/mortality, duration of
      intensive care unit stays and duration of medical ventilation. Univariate ordinal
      analyses were adopted to evaluate the correlations between outcome and treatment.
      A total of 104 patients with physician-diagnosed CRKP were involved in the study.
      The overall mortality rate was 25.0%. The majority of the infections (84; 80.8%)
      were hospital acquired. Critical infections received more than one active
      antibiotic as therapy. Patients treated with fosfomycin combinational therapy
      were less likely to fail therapy (OR: 4.71, 95% CI: 1.03-21.65, P=0.034) and
      tended to have a shorter duration of mechanical ventilation. Gender (OR: 4.35,
      95% CI: 1.08-3.60, P=0.037), history of chronic obstructive pulmonary disease
      (OR: 9.35, 95% CI: 0.06-0.19, P=0.007) and peripheral catheter use (OR: 3.00, 95%
      CI: 0.07-0.19, P=0.002) are risk factors for clinical outcome. Therefore, the use
      of fosfomycin combinational therapy for treatment of infection due to CRKP
      appears to be associated with improved survival rate.

PMID- 28450934
TI  - Microscopic surgery for pituitary adenomas to preserve the pituitary gland and
      stalk.
AB  - Surgery is the primary treatment of choice for all symptomatic pituitary adenomas
      except prolactinomas. Common postoperative complications include
      endocrinopathies, vision impairment and cerebrospinal fluid leak. The present
      study assessed 153 continuous microscopic surgeries for pituitary adenomas
      performed by an author of the present study between 2010 to 2014. Patients
      underwent either transphenoidal or transcranial surgery depending on their
      individual tumor characteristics. Five typical cases are presented in the present
      study and intraoperative identification and preservation of the gland and stalk
      were discussed. Postoperative complications were analyzed and compared with the
      literature. In the present analysis, 90.2% patients received transphenoidal
      surgery, and the rest underwent transcranial operation. Gross total resection was
      achieved in 81.2% patients in the transphenoidal group and 46.7% patients in the
      transcranial group. No new hypopituitarism or worsening of the pre-existing
      pituitary dysfunctions was detected. The most common postoperative endocrinopathy
      was diabetes insipidus (transphenoidal group, 4.3%; transcranial group, 26.7%).
      All patients were fully recovered prior to discharge. The findings indicated the
      importance of pituitary gland and stalk preservation during the microscopic
      surgery to minimize postoperative morbidity and mortality, without compromising
      the extent of tumor resection. Based on preoperative imaging characteristics and
      intraoperative observations, surgeons should try all possible means to preserve
      the pituitary stalk and gland during surgery in order to minimize postoperative
      endocrinopathies and improve quality of life.

PMID- 28450935
TI  - MicroRNA-138 inhibits hypoxia-induced proliferation of endothelial progenitor
      cells via inhibition of HIF-1alpha-mediated MAPK and AKT signaling.
AB  - Endothelial progenitor cells (EPCs) participate in angiogenesis by
      differentiating into endothelial cells (ECs) and may be developed to treat
      ischemia/reperfusion injury. MicroRNAs (miRs) are a type of non-coding RNA that
      are 18-25 nucleotides in length and serve a role in angiogenesis. It has been
      demonstrated that miR-138 regulates hypoxia-induced EC dysfunction. However, to
      the best of our knowledge, the exact role of miR-138 in the regulation of hypoxia
      induced EPCs has not previously been reported. In the present study, data
      collected from an MTT assay indicated that hypoxia treatment enhanced EPC
      proliferation, which was accompanied by an upregulation of hypoxia-inducible
      factor 1alpha (HIF-1alpha) expression. miR-138 overexpression inhibited hypoxia
      induced EPC proliferation and induced cell cycle arrest at the G1 stage. A
      mechanistic investigation revealed that miR-138 negatively regulated HIF-1alpha
      protein levels but did not affect HIF-1alpha mRNA levels in EPCs. Moreover,
      results from a dual luciferase reporter assay demonstrated that HIF-1alpha was a
      direct target of miR-138 in EPCs. Furthermore, upregulation of miR-138 suppressed
      the hypoxia-induced upregulation of HIF-1alpha. Downstream factors of HIF-1alpha
      were also investigated and it was observed that the upregulation of miR-138
      inhibited the hypoxia-induced upregulation of vascular endothelial growth factor,
      as well as the activity of mitogen-activated protein kinase and AKT signaling in
      EPCs. In summary, the present study suggested that miR-138 inhibits hypoxia
      induced EPC proliferation, possibly by inhibiting HIF-1alpha-mediated signaling.

PMID- 28450936
TI  - The traditional Korean herbal medicine Ga-Gam-Nai-Go-Hyan suppresses testosterone
      induced benign prostatic hyperplasia by regulating inflammatory responses and
      apoptosis.
AB  - Benign prostatic hyperplasia (BPH) is a pathological condition that affects the
      majority of men above the age of 50 years. Pharmacological agents are typically
      used to treat BPH; however, there are currently no pharmacological agents that
      are able to completely cure BPH without causing adverse side effects. As a result
      of these side effects, there is a great interest in developing effective herbal
      medicines that are able to inhibit the progression of BPH and are safe for long
      term use. Ga-Gam-Nai-Go-Hyan (GGN) is a traditional Korean herbal medicine that
      has been widely used to treat BPH; however, no biological studies have been
      performed to elucidate the efficacy of GGN. The aim of the present study was to
      evaluate the efficacy of GGN as a treatment for BPH. GGN administration was
      demonstrated to significantly decrease prostate weight (P<0.001), the relative
      prostate weight ratio (P<0.001) and the ratio of prostate weight to body weight
      (P<0.001). In addition, GGN treatment was revealed to suppress testosterone and
      dihydrotestosterone serum levels (P<0.001) and the growth of prostatic tissue.
      GGN also decreased the levels of the two inflammatory proteins (P<0.05),
      inducible nitric oxide synthase and cyclooxygenase-2, decreased the levels of the
      two apoptotic suppressors (P<0.05) B-cell lymphoma (Bcl)-2 and Bcl-xL and
      increased the levels of the pro-apoptotic factors (P<0.05) Bcl-2-associated X
      protein, caspase-3, caspase-8, Fas, Fas ligand and Fas-associated protein with
      death domain. The results of the present study suggested that GGN may have
      suppressive effects on the development of BPH and therefore have the potential to
      be used for treating BPH.

PMID- 28450937
TI  - Whole extracts of Radix Achyranthis Bidentatae and Radix Cyathulae promote
      angiogenesis in human umbilical vein endothelial cells in vitro and in zebrafish
      in vivo.
AB  - Although Radix Achyranthis Bidentatae (RAB) and Radix Cyathulae (RC) are from two
      different medicinal plants, they are both used as 'Niu-Xi', a widely used
      traditional Chinese medicine that is believed to stimulate menstruation and
      affect bone injury. Angiogenesis is actively involved in treating these
      illnesses. The aim of the present study was to investigate whether the whole
      extracts of RAB and RC possess pro-angiogenic effects. In order to examine this
      idea whole extracts of RAB and RC were extracted with boiling water followed by
      ethanol, respectively. Results from the MTT, wound healing and tube formation
      assays in human umbilical vein endothelial cells (HUVECs) in vitro revealed that
      the whole extracts of RAB and RC did not increase cell proliferation or tube
      formation, but enhanced cell migration. Their angiogenic effects were also
      confirmed in zebrafish in vivo via increasing the sprout numbers in the sub
      intestinal vessel. As determined by quantitative polymerase chain reaction, the
      whole extracts of RAB and RC both regulated the expression of cell migration
      related genes in zebrafish. It is concluded that the whole extracts of RAB and RC
      induced angiogenesis in HUVECs in vitro and in zebrafish in vivo via increasing
      cell migration.

PMID- 28450938
TI  - Isolation, culture and identification of human adipose-derived stem cells.
AB  - The aim of the present study was to improve methods for the isolation and
      identification of adipose-derived stem cells (ASCs). Human subcutaneous adipose
      tissue was collected during liposuction surgery, without ultrasound-assisted
      liposuction and other assisted techniques, and digested with 0.075% collagenase
      I. First (P1) and second (P2) passage ASCs were applied to the subsequent
      experiments. ASCs were observed under a microscope, the growth curves of the
      cells were assessed using a cell counting kit-8 assay and the membrane expression
      of cell surface antigens, including cluster of differentiation (CD)44, CD105 and
      CD45, were detected by flow cytometry. In addition, ASCs were induced to
      differentiate into lipocytes and osteocytes. Oil red staining was applied to
      examine adipogenic induction, whereas alkaline phosphatase (ALP) staining was
      used to assess osteogenic induction. Primary ASCs adhered to the culture vessel
      wall after 72 h, were fusiform in appearance at 5 days and exhibited stable
      growth with active proliferation. In total, 1*105 stem cells were gained per 50
      ml of lipo-aspirate. ASCs were plated in a 25 cm2 culture flask at a density of
      5*104/ml; the cells underwent the first logarithmic growth period after 72 h and
      grew to 90% confluence within 3 days. Flow cytometry demonstrated that the cells
      were highly positive for CD105 and CD44, and weakly positive for CD45; 18.6% of
      P1 cells and 90.7% of P2 cells were CD44+CD45-CD105+. Oil red and ALP staining
      were positive. The results of the present study suggested that ASCs may be
      considered a promising cell type for tissue engineering. Furthermore, the present
      study established an effective method for the isolation and identification of
      ASCs, which reduced damage to the stem cells and simplified the identification
      procedure.

PMID- 28450939
TI  - Genome-scale transcriptional analysis reveals key genes associated with the
      development of type II diabetes in mice.
AB  - Diabetes mellitus is one of the primary diseases that pose a threat to human
      health. The focus of the present study is type II diabetes (T2D), which is caused
      by obesity and is the most prevalent type of diabetes. However, genome-scale
      transcriptional analysis of diabetic liver in the development process of T2D is
      yet to be further elucidated. Microassays were performed on liver tissue samples
      from three-, six- and nine-week-old db/db mice with diabetes and db/m mice to
      investigate differentially expressed mRNA. Based on the results of genome-scale
      transcriptional analysis, five genes were screened in the present study:
      chromobox 8 (CBX8), de-etiolated homolog 1 and damage specific DNA binding
      protein 1 associated 1 (DDA1), Phosphoinositide-3-kinase regulatory subunit 6
      (PIK3R6), WD repeat domain 41 (WDR41) and Glycine Amidinotransferase (GATM). At
      three weeks of age, no significant differences in levels or ratios of expression
      were observed. However, at six and nine weeks, expression of CBX8, DDA1, PIK3R6
      and WDR41 was significantly upregulated (P<0.05) in the db/db model group
      compared with the control group, whereas GATM expression was significantly
      downregulated (P<0.05). These results suggest that T2D-related differential
      expression of genes becomes more marked with age, which was confirmed via reverse
      transcription-quantitative polymerase chain reaction. Genome-scale
      transcriptional analysis in diabetic mice provided a novel insight into the
      molecular. events associated with the role of mRNAs in T2D development, with
      specific emphasis upon CBX8, DDA1, PIK3R6, GATM and WDR41. The results of the
      present study may provide rationale for the investigation of the target genes of
      these mRNAs in future studies.

PMID- 28450941
TI  - Rapidly progressive rhino-orbito-cerebral mucormycosis in a patient with type 2
      diabetes: A case report.
AB  - With the ongoing economic development, lifestyle changes and an aging population,
      diabetes mellitus has be come one of the most prevalent chronic diseases in the
      world. Rhino-orbito-cerebral (ROC) mucormycosis is a rare, acute and
      angioinvasive fungal infection that can be fatal. Mucormycosis occurs exclusively
      in immunocompromised patients with diabetes mellitus and other types of
      immunodeficiency and has three subtypes: Rhino-maxillary, rhino-orbital and ROC
      mucormycosis. The present study reported on a case of ROC mucormycosis in a
      patient with diabetic ketoacidosis. In the present case, the pathogen afflicted
      all of the above organs, including the left eye, nasal cavity, hard palate and
      cerebrum.

PMID- 28450940
TI  - Langerhans' cell histiocytosis of the temporal bone: A case report.
AB  - Langerhansmporal histiocytosis (LCH) refers to a group of diseases that are
      characterized by the primary pathogenesis of an abnormal polyclonal proliferation
      of Langerhans cells that affect different structures of the human body, including
      the temporal bone. Thus far, the etiology of LCH remains unclear. Diagnosis of
      LCH is based on a synthetic analysis of the clinical presentations, as well as on
      features of imaging and histopathology. The clinical features, diagnosis,
      treatment and prognosis of LCH remain obscure, and temporal LCH is often confused
      with ear inflammatory lesions and malignant tumors. There are several therapeutic
      modalities for temporal bone LCH that include surgery, chemotherapy, radiotherapy
      and steroidal injections. The present study reports the case of an infant
      presenting a 1-month history of worsening left facial paralysis and a slowly
      enlarging post auricular mass followed by a 1-month history of postauricular
      swelling in the left ear. Computed tomography demonstrated a large mass of
      organized tissue. Moreover, the diagnosis of LCH was confirmed by
      histopathological and immunohistochemical examinations. The patient also suffered
      from multiple organ failure, including the liver, kidney, lymphatic system, skin,
      hematopoietic system and lungs. Following surgical intervention with
      mastoidotympanectomy, the parents of the patient refused further chemotherapy,
      and the patient succumbed to the disease ~6 months later.

PMID- 28450942
TI  - Immunohistochemical analysis of microsomal glutathione S-transferase 1 and
      clusterin expression in lens epithelial cells of patients with pseudoexfoliation
      syndrome.
AB  - Pseudoexfoliation syndrome (PEX) is an age-associated, sight disorder affecting
      elastic fibers in the eye and visceral organs but its exact etiology remains
      unknown. The purpose of the current study was to determine the morphology and
      ultrastructure of lens epithelial cells (LECs), and to use immunohistochemistry
      to examine localization of microsomal glutathione S-transferase 1 (MGST1) and
      clusterin. Anterior lens capsules were obtained from 24 patients (13 PEX and 11
      controls) who underwent phacoemulsification. Immunohistochemistry was performed,
      using antibodies against MGST1 and clusterin, to determine their expression. The
      morphology and ultrastructure of LECs were evaluated by light and transmission
      electron microscopy, respectively. The PEX LECs were characterized by
      significantly lower MGST1 (P=0.0001) and clusterin expression (P=0.0005) compared
      with the control group patients. PEX LECs were also observed to have
      significantly increased thickness compared with the control group patients
      (P=0.0002). The current findings suggest that low MGST1 and clusterin expression
      levels may be an early clinical indicator of PEX, and that oxidative stress may
      serve an important role, but that the specific etiology of this disease has yet
      to be revealed.

PMID- 28450943
TI  - Clinicopathological significance of ROCK1 and PIK3CA expression in nasopharyngeal
      carcinoma.
AB  - The aim of the present study was to determine the expression of rho-associated
      coiled-coil-containing protein kinase 1 (ROCK1) and phosphatidylinositol-4,5
      bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in nasopharyngeal
      carcinoma (NPC), and to assess the association between the expression of these
      proteins and the clinicopathological features of NPC. ROCK1 and PIK3CA
      expressions were assessed in a tissue microarray of sections prepared from the
      tumors of 81 patients with NPC using immunohistochemistry. Western blot analysis
      was used to detect ROCK1 and PIK3CA expression in NP69 and 5-8F cells. chi2
      analysis revealed that upregulation of ROCK1 was significantly associated with
      advanced N stage (P=0.032) cancer and increased PIK3CA expression was
      significantly associated with advanced N stage (P=0.027) and TNM stage (P=0.019)
      cancer. Furthermore, ROCK1 expression was significantly positively correlated
      with PIK3CA expression (P=0.01). Western blot analysis demonstrated that levels
      of ROCK1 (P<0.001) and PIK3CA (P=0.015) were significantly higher in 5-8F cells
      compared with NP69 cells. The results of the present study indicate that high
      levels of ROCK1 and PIK3CA expression may be associated with advanced stages in
      NPC.

PMID- 28450944
TI  - Evaluation of optimized magnetic resonance perfusion imaging scanning time window
      after contrast agent injection for differentiating benign and malignant breast
      lesions.
AB  - The aim of the study was evaluate the 3.0 T magnetic resonance (MR) perfusion
      imaging scanning time window following contrast injection for differentiating
      benign and malignant breast lesions and to determine the optimum scanning time
      window for increased scanner usage efficiency and reduced diagnostic adverse risk
      factors. A total of 52 women with breast abnormalities were selected for
      conventional MR imaging and T1 dynamic-enhanced imaging. Quantitative parameters
      [volume transfer constant (Ktrans), rate constant (Kep) and extravascular
      extracellular volume fraction (Ve)] were calculated at phases 10, 20, 30, 40 and
      50, which represented time windows at 5, 10, 15, 20 and 25 min, respectively,
      following injection of contrast agent. The association of the parameters at
      different phases with benign and malignant tumor diagnosis was analyzed. MR
      perfusion imaging was verified as an effective modality in the diagnosis of
      breast malignancies and the best scanning time window was identified: i) Values
      of Ktrans and Kep at all phases were statistically significant in differentiating
      benign and malignant tumors (P<0.05), while the value of Ve had statistical
      significance only at stage 10, but not at any other stages (P>0.05); ii) values
      of Ve in benign tumors increased with phase number, but achieved no obvious
      changes at different phases in malignant tumors; iii) the optimum scanning time
      window of breast perfusion imaging with 3.0 T MR was between phases 10 and 30
      (i.e., between 5 and 15 min after contrast agent injection). The variation trend
      of Ve values at different phases may serve as a diagnostic reference for
      differentiating benign and malignant breast abnormalities. The most efficient
      scanning time window was indicated to be 5 min after contrast injection, based on
      the observation that the Ve value only had statistical significance in diagnosis
      at stage 10. However, the optimal scanning time window is from 5 to 15 min
      following the injection of contrast agent, since that the variation trend of Ve
      is able to serve as a diagnostic reference.

PMID- 28450945
TI  - Bupivacaine effectively relieves inflammation-induced pain by suppressing
      activation of the NF-kappaB signalling pathway and inhibiting the activation of
      spinal microglia and astrocytes.
AB  - The pain induced by local acute inflammation results in mild to severe
      discomfort, in addition to the possibility of physiological dysfunction and
      psychiatric disorders, such as sleep disorders and depression. However, the
      pathogenesis of pain is yet to be fully elucidated. In the present study, the
      effects of bupivacaine were explored in rat models inflammatory pain in order to
      investigate the anti-pain mechanism of bupivacaine. Complete Freund's adjuvant
      (CFA) was injected into the right rear foot of the rats to establish a model of
      transient inflammation-induced pain. Rats were randomly divided into four groups
      (n=8): CFA, CFA plus bupivacaine, CFA plus saline and untreated. The mechanical
      withdrawal threshold (MWT) of the rats was detected prior to and following CFA
      injection, and the results demonstrated that the MWT in the right rear foot
      significantly decreased from the 1st day of CFA injection (P<0.01; n=8), as
      compared with the untreated controls. Bupivacaine treatment was demonstrated to
      significantly increase the MWT of rats treated with CFA stimulation, as compared
      with the CFA group (P<0.01). Rotarod testing was performed to assess the motor
      activity of the rats, and the results demonstrated no significant differences
      among the four groups (P>0.05). Furthermore, the respective body weights of the
      rats were determined every two days before and after CFA injection, and no
      significant differences were detected among the four groups (P>0.05). Western
      blot analysis was performed to analyze expression levels of IkappaB and nuclear
      factor (NF)-kappaB, and the results demonstrated that bupivacaine increased the
      expression of IkappaB and decreased the expression levels of NF-kappaB, as
      compared with the rats with CFA-induced inflammatory responses, suggesting that
      bupivacaine inhibited NF-kappaB activation in the dorsal horn of the lumbar
      spinal cord of the model rats. Furthermore, reverse transcription-quantitative
      polymerase chain reaction analysis was performed to analyze the expression levels
      of inflammatory cytokines, which demonstrated that bupivacaine significantly
      inhibited the expression of TNF-alpha, IL-1beta and IL-6, as compared with the
      untreated group (P<0.01). Moreover, bupivacaine treatment significantly decreased
      the expression of spinal microglial marker OX42 and astrocyte marker-glial
      fibrillary acidic protein, as compared with the rats in the CFA group (P<0.01).
      The present findings demonstrated that treatment with bupivacaine significantly
      decreased the activation of microglia and astrocytes in rat models of
      inflammatory pain. Therefore, the present results may provide clarification of
      the pathogenesis and mechanism of inflammation-induced pain and may provide novel
      therapeutic strategies for the clinical treatment of pain.

PMID- 28450946
TI  - Effect of vacuum sealing drainage on the expression of VEGF and miRNA-17-5p in
      seawater-immersed blast-injury wounds.
AB  - The aim of the present study was to compare and observe the expression levels of
      vascular endothelial growth factor (VEGF) and miRNA-17-5p during the treatment of
      seawater-immersed blast-injury wounds (SIBIW) under different conditions of
      vacuum sealing drainage (VSD), and to identify the optimized range of VSD
      treatment and partially explain its mechanisms. The bilateral hips and scapulae
      of experimental pigs (weight, 25-30 kg) were subjected to blast-injury wounds,
      followed by the seawater immersion. The animals then underwent conventional
      dressing treatment under 120, 180 and 240 mmHg VSD. Visual observation, in
      addition to histological, immunohistochemical and molecular biological techniques
      were applied to compare and observe the extent of wound healing and expression
      levels of VEGF and miRNA-17-5p. The wound healing of the VSD treatment group was
      improved compared with the control group, with 120 mmHg negative pressure
      producing the most marked effect. miR-17-5p expression was detected in the SIBIW
      granulation tissues. There was significant difference between each VSD treatment
      group and control group at each time point (P<0.05). Thus, the present results
      show that miR-17-5p can be expressed in SIBIW granulation tissues, and this
      effect is most evident under 120 mmHg negative pressure, which may inform the
      optimized negative range for the treatment of SIBIW.

PMID- 28450948
TI  - Preventative effects of fermented Chimonobambusa quadrangularis shoot on
      activated carbon-induced constipation.
AB  - The present study aimed to determine the preventative effects of fermented
      Chimonobambusa quadrangularis shoot (FCQS) on activated carbon constipation in
      Kun Ming mice. FCQS has a more loose fiber tissue structure than unfermented
      fresh C. quadrangularis shoot (CQS), which is preferable for relieving
      constipation. In mice fed with FCQS for 9 days the time from consumption to their
      first black stool defecation (117 min) was shorter than the control group (192
      min) and the CQS group (148 min); however, it was longer than the normal (85 min)
      and bisacodyl treatment (99 min) groups. The gastrointestinal transit of the FCQS
      group (73.8%) was increased, as compared with the control (37.9%) and CQS (61.7%)
      groups; however, it was decreased as compared with the normal (100%) and
      bisacodyl (88.3%) groups. By observing the hemotoxylin and eosin-stained section
      of mice intestine, it was demonstrated that FCQS reduced injury to the intestinal
      tract resulting from constipation and alleviated the damage caused to the
      intestinal villi over the effects observed in the CQS group. Furthermore, FCQS
      was also able to increase the serum levels of motilin, endothelin-1, vasoactive
      intestinal peptide and acetylcholinesterase compared with the control group. c
      Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF) mRNA
      and protein expression levels in the small intestinal cells of FCQS-fed mice were
      increased, as compared with CQS-fed mice. Transient receptor potential cation
      channel subfamily V member 1 (TRPV1) and nitric oxide synthase (NOS) expression
      levels of small intestinal cells of FCQS-fed mice were reduced, as compared with
      CQS-fed mice. These findings demonstrated that FCQS may induce improved
      preventative effects on constipation, compared with CQS.

PMID- 28450947
TI  - The inflammatory cytokine IL-22 promotes murine gliomas via proliferation.
AB  - Interleukin (IL)-22 is newly identified proinflammatory cytokine involved in the
      T helper (Th)17 and Th22 response. However, the possible role of IL-22 in glioma
      remains uncertain. The results of the present study demonstrated higher
      expression levels of IL-22 and the receptor IL-22BP in the brain of GL261 glioma
      inoculation mice, suggesting the regulatory role of IL-22 in glioma. Injection of
      IL-22 increased the severity of glioma in vivo and higher expression levels of IL
      6, IL-1beta and tumor necrosis factor (TNF)-alpha were detected in the brain
      using ELISA following IL-22 injection. To elucidate the mechanism underlying the
      effects of IL-22, the present study aimed firstly to determine the expression
      levels of IL-22 receptor in a glioma cell line via reverse transcription
      quantitative polymerase chain reaction. IL-22 treatment significantly increased
      the expression levels of signal transducer and activator of transcription (STAT)3
      and the mRNA expression levels of STAT6 compared with the vehicle control. These
      results suggested that IL-22 may activate the Janus kinase (JAK)/STAT signaling
      pathway in glioma. Furthermore, IL-22 positively regulated the proliferation of
      glioma, consistent with its role in vivo. Conversely, IL-22-deficient mice
      exhibited prolonged survival compared with wild-type (WT) mice, and the
      expression levels of inflammatory cytokines were decreased in the brain of IL-22
      knock-out (KO) mice compared with WT mice. Concordant with these results, it was
      observed that IL-22-neutralising antibody was able to increase the survival of
      mice with glioma and attenuate the disease by significantly reducing the cytokine
      levels in the brain. In conclusion, the results of the present study demonstrated
      that expression levels of IL-22 in the brain of mice with glioma may enhance
      symptoms due to the increased cytokine production of IL-6, IL-1beta and TNF
      alpha; this is consistent with IL-6/JAK/STAT signalling activation in vitro.
      Decreasing the expression levels of IL-22, achieved either with IL-22-KO mice or
      IL-22-neutralising antibody demonstrated protective effects on glioma
      development. Therefore, IL-22 may serve as a potential therapeutic target for
      glioma.

PMID- 28450949
TI  - Genetic variation in the 3'-untranslated region of PAK1 influences schizophrenia
      susceptibility.
AB  - The present study aimed to investigate the association of two polymorphisms
      (rs2844337 and rs11237200) in the P21 protein (cell division control protein
      42/Rac)-activated kinase 1 gene with susceptibility to schizophrenia (SCZ) in
      Chinese Zhuang and Chinese Han populations. A total of 700 patients with SCZ and
      700 healthy controls were recruited. Rs2844337 and rs11237200 polymorphisms were
      genotyped using Sequenom technology. A total of 591 patients completed the
      Positive and Negative Syndrome Scale (PANSS) assessment. Data were statistically
      analyzed using PLINK version 1.07 and SPSS version 17.0. In the Chinese Han
      population, the genotypic (P=0.038) and allelic (P=0.033) frequencies of the 3'
      untranslated region (UTR) genetic variation of rs2844337 in patients were
      significantly decreased compared to that in controls; these frequencies were
      significantly associated with SCZ susceptibility in the additive model
      (Padj=0.032) and in the recessive model (Padj=0.031). Moreover, the TG haplotype
      constructed by rs2844337 and rs11237200 polymorphisms remained significantly
      associated with SCZ risk following adjustment for gender and age and applying a
      Bonferroni correction in the Chinese Han population (Padj=0.003, PBC=0.009). The
      adjacent 5'-UTR genetic variation of rs11237200 was significantly associated with
      the total score (Padj=0.006), positive scale score (Padj=0.014) and general
      psychopathology scale scores (Padj=0.009) in the recessive model of the Chinese
      Han population. However, these polymorphisms were not significantly associated
      with SCZ susceptibility or the PANSS scores in the Chinese Zhuang population. In
      conclusion, variations in the PAK1 gene influenced the susceptibility and
      severity of the clinical symptoms of SCZ in the Chinese Han population
      investigated in the present study.

PMID- 28450950
TI  - Efficacy and tolerability of once-daily 160 mg valsartan in Chinese patients with
      mild to moderate hypertension.
AB  - The present multicentre, prospective, open-label, single treatment arm study (Val
      Perfect) examined the efficacy and tolerability of once-daily valsartan
      monotherapy (80 mg for two weeks, followed by 160 mg for eight weeks) in 195
      Chinese patients with mild to moderate hypertension, using office, home, and
      ambulatory blood pressure (BP) monitoring. Significant mean reductions (P<0.0001)
      were observed in office BP from baseline to week 10, with mean sitting systolic
      BP (MSSBP) and mean sitting diastolic BP (MSDBP) values of 15.6+/-12.3 and 11.1+/
      8.6 mmHg, respectively. The office BP control rate at week 10 was 56.9% (target
      MSSBP/MSDBP <130/80 mmHg for patients with type 2 diabetes or chronic kidney
      disease, <140/90 mmHg for others). Valsartan treatment significantly reduced mean
      24-h SBP/DBP (-6.1/-4.4 mmHg; both P<0.0001) and mean home-monitored SBP/DBP (
      13.3/-9.1 mmHg; both P<0.0001) at week 10. The incidence of adverse events (AEs)
      leading to discontinuation (1.5%) or drug-related AEs (3.1%) was low, with no
      instances of mortality or drug-related serious AEs. These results indicate that
      160 mg valsartan is safe and effective at lowering BP in Chinese patients with
      mild to moderate hypertension. The significant reductions in office-based and out
      of-office BP measures support the clinical relevance of moderate-dose valsartan
      monotherapy for effective 24-h BP control.

PMID- 28450951
TI  - Characteristics of carbapenemase-producing Klebsiella pneumoniae as a cause of
      neonatal infection in Shandong, China.
AB  - The goal of the present study was to examine the characteristics of carbapenem
      resistant Klebsiella pneumoniae as a cause of neonatal infection. A total of 37
      carbapenem-resistant Klebsiella pneumoniae-positive newborns hospitalized in
      Shandong Provincial Hospital, China between April 2011 and October 2013 were
      examined. Antibiotic susceptibility testing was performed using the agar dilution
      method and the Etest. Resistance genes were assessed by polymerase chain reaction
      (PCR) and sequencing. Pulsed-field gel electrophoresis (PFGE) and multi-locus
      sequence typing (MLST) were used to determine the genotypes and homology of these
      isolates. Plasmids were analyzed by PFGE and conjugation experiments. The outer
      membrane proteins were examined by PCR and SDS-PAGE. All of the isolates were
      revealed to be resistant to the third and fourth generation cephalosporins and
      piperacillin-tazobactam. Tigecycline, colistin, levofloxacin and amikacin were
      successful against all of the isolates. The antibiotic resistance rates of
      aztreonam, gentamicin, trimethoprim-sulfamethoxazole and fosfomycin were 13.51,
      48.64, 78.38 and 86.49%, respectively. Of the 37 cases, 25 isolates (67.57%) were
      blaNDM-1 positive, 13 isolates (35.14%) were blaIMP-4 positive and 1 isolate
      (2.70%) was blaIMP-8 positive. Two isolates carried both blaNDM-1 and blaIMP-4.
      The isolate carrying 2-4 plasmids and blaNDM-1 and blaIMP-4 was transferable
      between strains. SDS-PAGE data indicated that outer membrane proteins remained
      present. PFGE revealed 7 distinct clusters, and MLST reported the presence of
      ST20, ST17, ST54, ST705 and ST290 sequences, which indicated that there was clone
      and plasmid spread between newborns. The main resistance mechanism of carbapenem
      resistant Klebsiella pneumoniae was that the isolates expressed the carbapenemase
      resistance of blaNDM-1 and blaIMP-4 genes. The current study indicates that early
      detection of these genes may be helpful in infection prevention and control.

PMID- 28450952
TI  - MicroRNA-185 regulates spinal cord injuries induced by thoracolumbar spine
      compression fractures by targeting transforming growth factor-beta1.
AB  - The aims of the present study were to examine the expression of transforming
      growth factor (TGF)-beta1 and microRNA (miR)-185 in the bone tissue, blood and
      cerebrospinal fluid of patients with spinal cord injuries and to evaluate the
      regulation of spinal cord injuries by miR-185. A total of 44 patients with spinal
      cord injuries induced by thoracolumbar spine compression fractures, who were
      hospitalized at Luoyang Orthopedic-Traumatological Hospital between June 2012 and
      February 2015 were enrolled in the present study. Among the patients enrolled, 18
      underwent surgery between 1 and 7 days following fracture, and 26 patients
      underwent surgery between 8 and 14 days following fracture. Bone tissue,
      peripheral blood and cerebrospinal fluid were subsequently harvested from
      patients for analysis. Reverse transcription-quantitative polymerase chain
      reaction was performed to determine the expression of miR-185 and TGF-beta1 mRNA.
      Western blotting was performed to evaluate TGF-beta1 protein expression in bone
      tissue and ELISA was employed to quantify TGF-beta1 protein expression in the
      blood and cerebrospinal fluid. TGF-beta1 mRNA and protein levels in bone tissue,
      blood and cerebrospinal fluid from patients who underwent surgery 8-14 days post
      fracture were significantly higher than those who underwent surgery 1-7 days post
      fracture (P<0.05). By contrast, miR-185 levels were significantly lower in bone
      tissue, blood and cerebrospinal fluid from patients who underwent surgery 8-14
      days post-fracture compared with those who underwent surgery 1-7 days post
      fracture (P<0.05). The results of the present study desmonstrate that the
      upregulation of TGF-beta1 in the bone tissue, blood and cerebrospinal fluid of
      patients with spinal cord injuries induced by thoracolumbar spine compression
      fractures is correlated with the downregulation of miR-185. Furthermore, miR-185
      may target TGF-beta1, affecting its transcription and translation, indicating
      that it serves an important role in spinal cord injuries induced by thoracolumbar
      spine compression fractures.

PMID- 28450953
TI  - Association of nNOS and Rho-kinase with age-associated erectile dysfunction in
      Sprague-Dawley rats.
AB  - The present study aimed to investigate the changes of Rho-associated kinase (Rho
      kinase) and neuronal nitric oxide synthase (nNOS) expression in age-associated
      erectile dysfunction (ED) in Sprague-Dawley (SD) rats. A total of 100 intact male
      SD rats were divided into 20 groups according to their age (5-24 months; rats
      that were the same age in months were in the same group). Erectile response
      measurements were performed and the functional index intracavernosal
      pressure/mean arterial pressure (ICP/MAP) was tested, followed by detection of
      Rho-kinase and nNOS protein by western blot analysis. Finally, correlation
      analyses of the association between ICP/MAP and Rho-kinase, nNOS, or nNOS/Rho
      kinase, as well as between age and nNOS or Rho-kinase, were performed. The
      functional index ICP/MAP decreased with age in SD rats. Moreover, the expression
      of nNOS protein decreased, while Rho-kinase expression increased, indicating that
      the nNOS/Rho-kinase ratio decreased with age. The Pearson's correlation
      coefficients for the association between ICP/MAP and Rho-kinase, nNOS and
      nNOS/Rho-kinase ratio were -0.917, 0.853 and 0.937, respectively (P<0.01).
      Furthermore, nNOS was found to be significantly negatively correlated with age
      (r=-0.855; P<0.01), whereas Rho-kinase was positively correlated with age
      (r=0.943; P<0.01). Age-associated ED was therefore correlated with decreased nNOS
      and increased Rho-kinase, indicating that the nNOS/Rho-kinase ratio may be used
      as a candidate indicator of age-associated ED.

PMID- 28450954
TI  - Downregulation of a novel long non-coding RNA, LOC389332, is associated with poor
      prognosis and tumor progression in clear cell renal cell carcinoma.
AB  - It has been demonstrated that various long non-coding RNAs (lncRNAs) may have key
      roles in various types of cancer. Clear cell renal cell carcinoma (ccRCC) is the
      most common subtype of all RCCs, accounting for 70-80% of all cases. The present
      study identified a novel lncRNA and investigated its clinical significance and
      physiological function in ccRCC. The expression pattern of the novel lncRNA
      LOC389332 in 30 ccRCC tissue samples was examined using reverse-transcription
      quantitative polymerase chain reaction. The results demonstrated that LOC389332
      expression was markedly lower in ccRCC tissues compared with that in matched
      adjacent non-tumor tissues. Of note, downregulation of LOC389332 expression was
      significantly associated with the tumor American Joint Commission on Cancer stage
      (P=0.001), Fuhrman grade (P=0.001) and lymph node metastasis (P<0.001).
      Furthermore, patients with ccRCC with lower levels of LOC389332 expression had a
      shorter overall survival time than those with higher LOC389332 expression. A gain
      of-function study was used to evaluate the biological function of LOC389332 in
      ccRCC and the results suggested that restoration of LOC389332 expression
      inhibited the growth and migration of the 786-O and 769-P cell lines. Therefore,
      the results of the present study demonstrated that LOC389332 is a novel lncRNA
      involved in ccRCC progression and may be a potential diagnostic and prognostic
      biomarker. Ectopic overexpression of LOC389332 may represent a therapeutic
      strategy for ccRCC.

PMID- 28450955
TI  - alpha- and beta-Naphthoflavone synergistically attenuate H2O2-induced neuron SH
      SY5Y cell damage.
AB  - Previous studies have demonstrated an association between neurological diseases
      and oxidative stress (OS). Naphthoflavone is a synthetic derivative of naturally
      occurring flavonoids that serves an important role in the treatment and
      prevention of OS-related diseases. The current study was designed to apply alpha-
      and beta-Naphthoflavone individually and in combination to counteract the
      detrimental effects of OS on neurons in vitro. Neuronal SH-SY5Y cells were
      subjected to 20 uM H2O2, followed by exposure to 20 uM alpha-Naphthoflavone
      and/or 10 uM beta-Naphthoflavone. Results indicated that alpha- and beta
      Naphthoflavone effectively antagonized the apoptosis-promoting effect of H2O2 on
      neuronal SH-SY5Y cells, and that beta-Naphthoflavone significantly (P<0.05)
      reversed H2O2-inhibited cell viability. Notably, co-treatment of alpha- and beta
      Naphthoflavone reversed the H2O2-induced apoptosis rate elevation and cell
      viability reduction. Further analysis demonstrated that H2O2 inhibited the
      activities of antioxidant enzymes including catalase, superoxide dismutase and
      glutathione peroxidase, but this was reversed by the co-treatment with alpha- and
      beta-Naphthoflavone and selectively enhanced by the treatment with alpha- or beta
      Naphthoflavone. H2O2-stimulated p38 mitogen-activated protein kinase activation
      was repressed following treatment with alpha- and/or beta-Naphthoflavone, along
      with a decreased expression of the apoptosis-related factors and inhibited
      caspase-3 activation. In conclusion, co-treatment with alpha- and beta
      Naphthoflavone minimized H2O2-led neuron damage compared with treatment with
      alpha- or beta-Naphthoflavone, suggesting a synergetic effect between alpha- and
      beta-Naphthoflavone. This indicates that utilizing alpha- and beta-Naphthoflavone
      together in the clinical setting may provide a novel therapeutic for neurological
      disease.

PMID- 28450956
TI  - VanWyk-Grumbach syndrome in a male pediatric patient: A rare case report and
      literature review.
AB  - Primary hypothyroidism usually leads to retardation of linear growth and delay or
      even arrest of puberty in juvenile patients. In rare cases, pediatric patients
      with hypothyroidism may present with signs of VanWyk-Grumbach's syndrome (VWGS),
      which includes juvenile hypothyroidism, delayed bone age and pseudoprecocious
      puberty. The present study reported on a rare case of VWGS and other
      complications, including obesity, short stature, hepatomegaly and pituitary
      hyperplasia. In addition, a comprehensive literature review was performed to
      illustrate the treatment and outcome of VWGS in pediatric patients. The present
      study contributed to the current knowledge regarding the diagnosis and treatment
      of VWGS in pediatric patients.

PMID- 28450957
TI  - Iodine-131 therapy alters the immune/inflammatory responses in the thyroids of
      patients with Graves' disease.
AB  - The aim of the present study was to evaluate the serum levels of interleukin-6
      (IL-6), CXC chemokine ligand-10 (CXCL-10) and intercellular adhesion molecule-l
      (ICAM-1) in patients with Graves' disease (GD) following iodine-131 (131I)
      therapy. A total of 30 patients with GD participated in the present study. Serum
      cytokine levels were measured with ELISA, and correlation analyses were
      performed. Serum levels of IL-6, CXCL-10 and ICAM-1 were significantly higher in
      patients with GD prior to treatment than those in the control subjects (P<0.01).
      Following 131I therapy, the serum levels of IL-6 and CXCL-10 in patients with GD
      were markedly increased within the first week, gradually decreased to the
      pretreatment level in the subsequent six months and decreased further at 18
      months post-treatment. However, the serum levels of IL-6 and CXCL-10 in patients
      with GD at 18 months following 131I therapy remained significantly higher than in
      control subjects (P<0.01). Conversely, serum ICAM-1 levels in patients with GD
      were gradually increased in the 12 months following 131I therapy and reached a
      relatively stable level thereafter. Furthermore, the Pearson's correlation
      analysis indicated that the serum levels of IL-6, CXCL-10 and ICAM-1 were not
      associated with free triiodothyronine, the free thyroxine index, and thyroid
      stimulating hormone in these patients. 131I therapy was able to alter the
      immune/inflammatory responses in the thyroids of patients with GD. However, these
      cytokines (IL-6, CXCL-10, and ICAM-1) are not associated with thyroid function;
      therefore, they cannot be used as prognostic markers for the 131I therapy of GD.

PMID- 28450958
TI  - Upregulation of OLR1 and IL17A genes and their association with blood glucose and
      lipid levels in femoropopliteal artery disease.
AB  - Oxidized low-density lipoprotein receptor 1 (OLR1) and interleukin 17A (IL17A)
      have pro-inflammatory roles in the development of cardiovascular disorders. The
      present study evaluated the association of OLR1 and IL17A and their polymorphisms
      with the development of femoropopliteal (FP) artery disease. The mRNA expression
      of OLR1 and IL17A in peripheral blood mononuclear cells as well as the frequency
      of OLR1 rs11053646 and IL17A rs8193037 and rs3819025 polymorphisms were assessed
      by polymerase chain reaction in 70 patients with FP artery disease and 80 age
      matched disease-free controls. Furthermore, the levels of plasma cytokines were
      assessed by multiplex immunoassay. OLR1 and IL17A mRNA expression was
      significantly higher in patients with FP artery disease compared with that in
      controls (P<0.001). No significant difference was observed in the genotypic
      frequencies of OLR1 rs11053646 (P=0.87) or in IL17A rs8193037 and rs3819025
      (P=0.80 and 0.92, respectively) polymorphisms between patients with FP artery
      disease and controls. Plasma IL4, -6, -10, -22, -31 and -33 as well as soluble
      cluster of differentiation 40 ligand and tumor necrosis factor-alpha levels were
      significantly increased among FP artery disease patients compared with controls
      (P<0.05). Furthermore, OLR1 expression was positively correlated with
      triglyceride (r=0.463, P<0.001), low-density lipoprotein cholesterol (r=0.507,
      P<0.001) and total cholesterol levels (r=0.357, P=0.006) in patients with FP
      artery disease. To the best of our knowledge, the present study was the first to
      identify an association between OLR1 and IL17A genes and FP artery disease. OLR1
      and IL17A mRNA transcripts may be associated with blood lipid parameters and with
      the development of FP artery disease.

PMID- 28450959
TI  - Changes in liver stiffness and its associated factors during oral antiviral
      therapy in Chinese patients with chronic hepatitis B.
AB  - The present study aimed to assess improvements in liver stiffness determined by
      transient elastography and associated factors in Chinese patients with chronic
      hepatitis B (CHB) during long-term treatment with oral antiviral drugs. A total
      of 334 consecutive Chinese patients with CHB who underwent oral antiviral therapy
      and received at least two liver stiffness measurements (LSMs) at the First
      Hospital of Jilin University (Changchun, China) from December 2012 to February
      2015 were enrolled in the present study. The cohort included 201 patients without
      liver cirrhosis (group 0) and 133 patients with liver cirrhosis (group 1). Each
      patient was subjected to LSM twice with an interval of 6 months. The mean initial
      liver stiffness values were 14.01+/-9.37 and 21.59+/-10.25 kPa for patients in
      group 0 and group 1, respectively (P<0.001). Multivariate analysis revealed that
      higher aspartate aminotransferase and lower alanine aminotransferase levels at
      baseline as well as higher alpha-fetoprotein levels at follow-up (24 weeks) were
      associated with a greater decline of liver stiffness in group 0. Furthermore, a
      higher liver stiffness at baseline and a longer course of antiviral therapy prior
      to the initial LSM were significantly correlated with a reduction of liver
      stiffness, whereas higher total bilirubin levels at follow-up contributed to
      increased liver stiffness in group 1. In conclusion, LSM at the beginning and the
      end of a 24-week observation period showed that antiviral drug therapy
      significantly improved in group 1, while a marked decreasing trend was also
      observed in group 0. In group 0, the reduction of liver stiffness was correlated
      with liver inflammation, whereas in group 1, it was correlated with the treatment
      duration prior to the initial LSM and serum levels of hepatitis B virus DNA.
      Furthermore, a higher liver stiffness at baseline was associated with a greater
      reduction of liver stiffness in each group.

PMID- 28450960
TI  - Feasibility of improving platelet-rich plasma therapy by using chitosan with high
      platelet activation ability.
AB  - Platelet-rich plasma (PRP) is blood plasma containing a high number of platelets
      that release growth factors for wound healing and tissue regeneration. In the
      present study, the feasibility of improving PRP therapy by using chitosan that
      exhibits high platelet activation ability was investigated. A total of 13
      chitosan samples with different molecular weight (Mw) and degree of deacetylation
      (DDA) were individually added to blood samples of rats and the amount of growth
      factors, albumin and fibrinogen in plasma was measured. To examine the influence
      of plasma activated by chitosan on the proliferation of fibroblasts and adipose
      tissue-derived stromal cells (ASCs), the plasma was added to the culture medium
      of human fibroblasts and adipose tissue-derived stromal cells. Chitosan with a
      DDA of >75% increased the release of platelet factor 4 into the plasma. The
      amount of growth factors released into the plasma and platelet activation varied
      depending on the Mw and DDA, while albumin and fibrinogen were hardly affected.
      The proliferation rate was highest when using plasma activated by chitosan with a
      DDA of 75-85% and an Mw of 50,000-190,000 Da. These results suggested that the
      effectiveness of PRP therapy may be improved by using chitosan with a DDA of 75
      85% and an Mw of 50,000-190,000 Da.

PMID- 28450961
TI  - Evaluation of hip abductor and adductor strength in the elderly: a reliability
      study.
AB  - BACKGROUND: In elderly individuals an increased muscle strength contributes to
      the diminution of the falls risk and associated adverse events. An increasing
      interest in lateral control exists due to the fatal consequences of postero
      lateral falls. Therefore a proper assessment of frontal plane hip muscle strength
      in elderly is important but remains challenging. Therefore we aimed to
      investigate the feasibility and repeatability of a hip abductor and adductor
      maximum voluntary isometric strength (MVIS) and rate of force generation (RFG)
      test in elderly. This represents an initial step in the development process of a
      new and clinically relevant test that could lead to more specific treatment
      protocols for this population. METHODS: In this measurement focused study hip
      abduction (ABD) and adduction (ADD) MVIS and RFG were tested twice within one to
      three hours with a dynamometer fixed to a custom made frame in a geriatric
      population including fallers and non-fallers. Intraclass correlation coefficient
      (ICCagreement), standard error of measurement (SEM), and smallest detectable
      difference (SDD) were determined. RESULTS: All recruited persons (N = 76; mean
      age (SD) 80.46 (7.05) years old) completed the tests. The average time needed to
      complete the strength tests was 10.58 min. (1.56) per muscle group. The
      reliability of the hip ABD and ADD was high with ICC'sagreement ranging from 0.83
      to 0.97. The SDD varied between 18.1 and 81.8% depending on the muscle group and
      type of strength that was evaluated. CONCLUSION: Hip abductor and adductor
      strength measures in older person are feasible and reliable. However, the
      significance of moderate changes in these measurements may be limited by the
      large SDD and SEM. Therefore, physical therapist should be careful when using
      this measure for assessing the progress of an individual person in a daily
      clinical use.

PMID- 28450962
TI  - Occurrences of Sinolagomys (Lagomorpha) from the Valley of Lakes (Mongolia).
AB  - The genus Sinolagomys is an early representative of the family Ochotonidae,
      appearing first in the late early Oligocene of Central Asia. It is known in China
      from Shargaltein Tal, Taben Buluk, Ulan Tatal, and northern Junggaria, and a few
      specimens from Tatal Gol, Mongolia have been published. For most occurrences, the
      genus is not represented by many specimens. Extensive studies in the Valley of
      Lakes, Central Mongolia, have produced a large number of sinolagomyin fossils
      spanning at least 10 million years and belonging to five species: Sinolagomys
      kansuensis, Sinolagomys major, Sinolagomys gracilis, Sinolagomys ulungurensis,
      and Sinolagomys badamae sp. nov. Descriptions of these are given, as well as
      definition of the new species. Sinolagomyins flourished during the late Oligocene
      and early Miocene and came to occupy vast territories from China through Mongolia
      and Kazakhstan. The evolution of this ochotonid group is characterized by
      increasing taxonomic diversity and progressive development of rootless cheek
      teeth.

PMID- 28450963
TI  - The record of Aplodontidae (Rodentia, Mammalia) in the Oligocene and Miocene of
      the Valley of Lakes (Central Mongolia) with some comments on the morphologic
      variability.
AB  - The present publication reports new discoveries of Oligocene and early Miocene
      aplodontid rodents from the Taatsiin Gol area (Valley of Lakes) in Mongolia. The
      fossil aplodontids recovered in this area are mainly composed of dental remains,
      some fragmentary jaws plus one partially preserved skull. Aplodontid rodents have
      been found from the early Oligocene (local biozone A) to the early middle Miocene
      (local biozone D). Altogether, eight taxa belonging to five genera have been
      identified in the investigated deposits: Ninamys arboraptus, Ninamys kazimierzi,
      Promeniscomys cf. sinensis, Prosciurus? mongoliensis and Prosciurus? sp. nov. in
      the early Oligocene; N. arboraptus, Proansomys badamae sp. nov. and Ansomyinae
      indet. in the late Oligocene; and Ansomys sp.1 in the early Miocene. In addition,
      although outside of the topic of the present special issue, one additional taxon,
      Ansomys sp.2, is reported from the ?middle Miocene. The material of aplodontids
      is usually relatively scarce in Asian localities. For the first time, with a
      sample size of 81 specimens, the material from Central Mongolia (mainly from the
      Oligocene) now allows a more accurate description of the morphological and size
      variability and resolves some systematic problems. The study of these aplodontids
      reveals that they are more abundant and diverse in the early Oligocene and that
      the diversity decreases during the late Oligocene and Miocene. One hypothesis, to
      explain the opposite diversity trend observed previously for sciurids in the same
      region, is that both Sciuromorpha families might have competed for the same
      resources from the early Oligocene to the middle Miocene in Central Mongolia.

PMID- 28450964
TI  - Cricetidae (Rodentia, Mammalia) from the Oligocene of the Valley of Lakes
      (Mongolia): the genera Aralocricetodon, Eocricetodon, Bagacricetodon, Witenia and
      Paracricetodon.
AB  - We describe the remains of Aralocricetodon Bendukidze, 1993; Bagacricetodon Gomes
      Rodrigues et al., 2012; Eocricetodon Wang, 2007; Witenia de Bruijn et al., 2003
      and Paracricetodon Schaub, 1925 (Cricetidae, Rodentia, Mammalia) from the
      Taatsiin Gol and Taatsiin Tsagaan Nuur areas (Mongolia). The studied material
      (comprising 128 teeth) stems from 9 localities and 23 fossil layers spanning a
      time interval from ~33 to ~24 Ma (early to late Oligocene) and covering the
      biozones from A to C1. The general dental pattern between the species from the
      early and late Oligocene differed. The occlusal pattern of the molars was more
      complicated and the crowns were lower during the early versus late Oligocene.
      This indicates a change in diet towards more abrasive plants. Several of the
      studied species were common in both Europe and Asia Minor during the early
      Oligocene. The species collected from the late Oligocene have also been recorded
      in Kazakhstan and China. This indicates an interesting biogeographical pattern
      that merits future study.

PMID- 28450965
TI  - Oligocene stratigraphy across the Eocene and Miocene boundaries in the Valley of
      Lakes (Mongolia).
AB  - Cenozoic sediments of the Taatsiin Gol and TaatsiinTsagaan Nuur area are rich in
      fossils that provide unique evidence of mammal evolution in Mongolia. The strata
      are intercalated with basalt flows. 40Ar/39Ar data of the basalts frame the time
      of sediment deposition and mammal evolution and enable a composite age chronology
      for the studied area. We investigated 20 geological sections and 6 fossil
      localities of Oligocene and early Miocene deposits from this region. Seventy
      fossil beds yielded more than 19,000 mammal fossils. This huge collection
      encompasses 175 mammal species: 50% Rodentia, 13% Eulipotyphla and
      Didelphomorphia, and 12% Lagomorpha. The remaining 25% of species are distributed
      among herbivorous and carnivorous large mammals. The representation of lower
      vertebrates and gastropods is comparatively poor. Several hundred SEM images
      illustrate the diversity of Marsupialia, Eulipotyphla, and Rodentia dentition and
      give insight into small mammal evolution in Mongolia during the Oligocene and
      early Miocene. This dataset, the radiometric ages of basalt I (~31.5 Ma) and
      basalt II (~27 Ma), and the magnetostratigraphic data provide ages of mammal
      assemblages and time ranges of the Mongolian biozones: letter zone A ranges from
      ~33 to ~31.5 Ma, letter zone B from ~31.5 to ~28 Ma, letter zone C from ~28 to
      25.6 Ma, letter zone C1 from 25.6 to 24 Ma, letter zone C1-D from 24 to ~23 Ma,
      and letter zone D from ~23 to ~21 Ma.

PMID- 28450966
TI  - Oligocene and early Miocene mammal biostratigraphy of the Valley of Lakes in
      Mongolia.
AB  - The Taatsiin Gol Basin in Mongolia is a key area for understanding the evolution
      and dispersal of Central Asian mammal faunas during the Oligocene and early
      Miocene. After two decades of intense fieldwork, the area is extraordinarily well
      sampled and taxonomically well studied, yielding a large dataset of 19,042
      specimens from 60 samples. The specimens represent 176 species-level and 99 genus
      level taxa comprising 135 small mammal species and 47 large mammals. A detailed
      lithostratigraphy and new magnetostratigraphic and radiometric datings provide an
      excellent frame for these biotic data. Therefore, we test and evaluate the
      informal biozonation scheme that has been traditionally used for biostratigraphic
      correlations within the basin. Based on the analysis of the huge dataset, a
      formalised biostratigraphic scheme is proposed. It comprises the Cricetops
      dormitor Taxon Range Zone (Rupelian), subdivided into the Allosminthus khandae
      Taxon Range Subzone and the Huangomys frequens Abundance Subzone, the Amphechinus
      taatsiingolensis Abundance Zone (early Chattian), the Amphechinus major Taxon
      Range Zone (late Chattian), subdivided into the Yindirtemys deflexus Abundance
      Subzone and the Upper Amphechinus major T. R. Z., and the Tachyoryctoides
      kokonorensis Taxon Range Zone (Aquitanian). In statistical analyses, samples
      attributed to these biozones form distinct clusters, indicating that each biozone
      was also characterised by a distinct faunal type.

PMID- 28450967
TI  - Geochemistry and mineralogy of the Oligo-Miocene sediments of the Valley of
      Lakes, Mongolia.
AB  - The Valley of Lakes is approximately a 500-km elongate depression in Central
      Mongolia, where Eocene to Miocene continental sediments are long known for their
      outstanding fossil richness. The palaeontological record of this region is an
      exceptional witness for the evolution of mammalian communities during the
      Cenozoic global cooling and regional aridification. In order to precisely
      elucidate the climatic evolution of the region, we studied the mostly
      siliciclastic sediments with several levels of paleosols for their sedimentology,
      mineralogy, major and trace element composition and delta13C and delta18O
      composition. The obtained results show that temperate hydrothermal fluids induced
      a strong illitization of the fluvial and lacustrine sediments. This finding
      contradicts the current conceptual view that the fine fraction of the sediments
      is of aeolian origin. Moreover, the diagenetic growth of illite resulted in a
      strong overprinting of the sediments and, subsequently, largely disturbed the
      pristine mineralogical and geochemical composition of the sediments that could
      have carried any palaeo-climatic information. An exception is the delta13C (and
      delta18O) isotope values of authigenic carbonate found in calcrete horizons that
      still record the ambient climatic conditions prevailing during paleosol
      formation. Our novel delta13C and delta18O record suggests an early Oligocene
      aridification in Central Asia at ~31 Ma, whereas the Oligocene glacial maximum
      shows no increase in aridification. A second, regional-scale aridification occurs
      at ~25 Ma and corresponds to a late Oligocene marked mammalian turnover in the
      Valley of Lakes sediments.

PMID- 28450968
TI  - Visible-Light-Controlled Oxidation of Glucose using Titania-Supported Silver
      Photocatalysts.
AB  - The visible-light-mediated photo-catalytic selective valorisation of glucose
      using TiO2-supported Ag nanoparticles is shown for the first time. The
      optimisation of the catalyst composition, substrate-to-catalyst ratio and
      reaction medium proved that a near total suppression of the mineralisation
      pathway could be achieved with a selectivity to partial oxidation products and
      small-chain monosaccharides as high as 98 %. The primary products were determined
      to be gluconic acid, arabinose, erythrose, glyceraldehyde and formic acid. Under
      UVA light, the selectivity to organics decreases because of the production of CO2
      from mineralisation. A reaction mechanism is proposed based on an alpha-scission
      process combined with the Ruff degradation reaction, which explains the presence
      of the oxidation products, the smaller carbohydrates and formic acid. X-ray
      photoelectron spectroscopy, UV/Vis spectroscopy and microscopy studies showed the
      presence of plasmonic 4 nm particles of silver that were oxidised to silver oxide
      over the course of the reaction, and recycling studies revealed that this was not
      detrimental to activity.

PMID- 28450969
TI  - Characterization of Carboxylic Acid Reductases as Enzymes in the Toolbox for
      Synthetic Chemistry.
AB  - Carboxylic acid reductase enzymes (CARs) meet the demand in synthetic chemistry
      for a green and regiospecific route to aldehydes from their respective carboxylic
      acids. However, relatively few of these enzymes have been characterized. A
      sequence alignment with members of the ANL (Acyl-CoA synthetase/ NRPS adenylation
      domain/Luciferase) superfamily of enzymes shed light on CAR functional dynamics.
      Four unstudied enzymes were selected by using a phylogenetic analysis of known
      and hypothetical CARs, and for the first time, a thorough biochemical
      characterization was performed. Kinetic analysis of these enzymes with various
      substrates shows that they have a broad but similar substrate specificity.
      Electron-rich acids are favored, which suggests that the first step in the
      proposed reaction mechanism, attack by the carboxylate on the alpha-phosphate of
      adenosine triphosphate (ATP), is the step that determines the substrate
      specificity and reaction kinetics. The effects of pH and temperature provide a
      clear operational window for the use of these CARs, whereas an investigation of
      product inhibition by NADP+, adenosine monophosphate, and pyrophosphate indicates
      that the binding of substrates at the adenylation domain is ordered with ATP
      binding first. This study consolidates CARs as important and exciting enzymes in
      the toolbox for sustainable chemistry and provides specifications for their use
      as a biocatalyst.

PMID- 28450970
TI  - Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium
      of patients with COPD.
AB  - BACKGROUND: Goblet cell metaplasia, a common feature of chronic obstructive
      pulmonary disease (COPD), is associated with mucus hypersecretion which
      contributes to the morbidity and mortality among patients. Transcription factors
      SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2
      (FOXA2) regulate goblet cell differentiation. This study aimed to (1) investigate
      DNA methylation and expression of SPDEF and FOXA2 during goblet cell
      differentiation and (2) compare this in airway epithelial cells from patients
      with COPD and controls during mucociliary differentiation. METHODS: To assess DNA
      methylation and expression of SPDEF and FOXA2 during goblet cell differentiation,
      primary airway epithelial cells, isolated from trachea (non-COPD controls) and
      bronchial tissue (patients with COPD), were differentiated by culture at the air
      liquid interface (ALI) in the presence of cytokine interleukin (IL)-13 to promote
      goblet cell differentiation. RESULTS: We found that SPDEF expression was induced
      during goblet cell differentiation, while FOXA2 expression was decreased.
      Importantly, CpG number 8 in the SPDEF promoter was hypermethylated upon
      differentiation, whereas DNA methylation of FOXA2 promoter was not changed. In
      the absence of IL-13, COPD-derived ALI-cultured cells displayed higher SPDEF
      expression than control-derived ALI cultures, whereas no difference was found for
      FOXA2 expression. This was accompanied with hypomethylation of CpG number 6 in
      the SPDEF promoter and also hypomethylation of CpG numbers 10 and 11 in the FOXA2
      promoter. CONCLUSIONS: These findings suggest that aberrant DNA methylation of
      SPDEF and FOXA2 is one of the factors underlying mucus hypersecretion in COPD,
      opening new avenues for epigenetic-based inhibition of mucus hypersecretion.

PMID- 28450971
TI  - Epigenetic changes in blood leukocytes following an omega-3 fatty acid
      supplementation.
AB  - BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 FAs) have several beneficial
      effects on cardiovascular (CV) disease risk factors. These effects on CV risk
      profile may be mediated by several factors, including epigenetic modifications.
      Our objective is to investigate, using genome-wide DNA methylation analyses,
      methylation changes following an n-3 FA supplementation in overweight and obese
      subjects and to identify specific biological pathways potentially altered by the
      supplementation. RESULTS: Blood leukocytes genome-wide DNA methylation profiles
      of 36 overweight and obese subjects before and after a 6-week supplementation
      with 3 g of n-3 FAs were compared using GenomeStudio software. After
      supplementation, 308 CpG sites, assigned to 231 genes, were differentially
      methylated (FDR-corrected Diffscore >=?13?~ P <= 0.05). Using Ingenuity Pathway
      Analysis system, a total of 55 pathways were significantly overrepresented
      following supplementation. Among these pathways, 16 were related to inflammatory
      and immune response, lipid metabolism, type 2 diabetes, and cardiovascular
      signaling. Changes in methylation levels of CpG sites within AKT3, ATF1, HDAC4,
      and IGFBP5 were correlated with changes in plasma triglyceride and glucose levels
      as well as with changes in the ratio of total cholesterol/HDL-cholesterol
      following the supplementation. CONCLUSIONS: These data provide key differences in
      blood leukocytes DNA methylation profiles of subjects following an n-3 FA
      supplementation, which brings new, potential insights on metabolic pathways
      underlying the effects of n-3 FAs on CV health.

PMID- 28450972
TI  - Circulating unmethylated insulin DNA as a potential non-invasive biomarker of
      beta cell death in type 1 Diabetes: a review and future prospect.
AB  - BACKGROUND: The early detection of type 1 diabetes (T1D) largely depends on a
      reliable approach to monitor beta cell loss. An effective way to evaluate the
      decline of beta cell mass would allow early preventative intervention to preserve
      insulin secretion. MAIN BODY: Recent progress in the development of novel
      biomarkers, based on tissue-specific methylation patterns, has inspired relevant
      studies in T1D. In this review, we focus on the application of circulating beta
      cell-derived unmethylated insulin (INS) DNA. Circulating beta cell-derived
      unmethylated INS DNA has a potential clinical value for the early detection of
      T1D, surveillance of islet transplantation rejection, and evaluation of response
      to therapy. Utilizing differentiated methylation patterns in different organs and
      employing a wide variety of molecular technologies also provide insights into the
      interrogation of biomarkers in other diseases with massive tissue-specific cell
      loss. CONCLUSION: Circulating unmethylated INS DNA is a promising molecular
      biomarker for the early detection of T1D.

PMID- 28450973
TI  - The Field of View is More Useful in Golfers than Regular Exercisers.
AB  - Superior visual attention skills are vital for excellent sports performance. This
      study used a cognitive skills approach to examine expert and novice differences
      in a visual spatial attention task. Thirty-two males aged 18 to 42 years
      completed this study in return for course credit or monetary incentive.
      Participants were expert golfers (N = 18) or exercise controls (N = 14). Spatial
      attention was assessed using the useful field of view task which required
      participants to locate a target shown 10 degrees , 20 degrees , and 30 degrees 
      of eccentricity from centre in very brief presentations. At each degree of
      eccentricity, golfers were more accurate at locating the target than the exercise
      controls. These results provide support for the broad transfer hypothesis by
      demonstrating a link between golf expertise and better performance on an
      objective measure of spatial attention skills. Therefore, it appears that sports
      expertise can transfer to expertise in non-sport related tasks.

PMID- 28450974
TI  - Response Preparation, Response Conflict, and the Effects of Irrelevant Flanker
      Stimuli.
AB  - The present study explored how response preparation modulates the effects of
      response conflict as induced by irrelevant flanker stimuli. In Experiments 1 and
      2, an unreliable response cue (i.e., valid in 75% of trials but invalid in 25% of
      trials) preceded the stimulus display containing a target stimulus and different
      types (i.e., identical, neutral, compatible, or incompatible) flanker stimuli. In
      Experiment 3, a fully reliable response cue (i.e., valid in 100% of trials) or a
      neutral cue preceded the stimulus display. There were two major findings. First,
      valid response cues always improved performance in terms of speed and accuracy
      when compared to invalid or neutral cues, indicating that the cues were used to
      selectively prepare the indicated response. Second, response preparation with
      unreliable response cues did not modulate flanker-induced response conflict in
      reaction times (RTs; and not consistently in error percentages), whereas response
      preparation with reliable cues eliminated flanker-induced response conflict.
      According to these results, only extreme levels of response preparation modulate
      (flanker-induced) response conflict. The results of computer simulations suggest
      some boundary conditions for our conclusion.

PMID- 28450975
TI  - Is Attentional Resource Allocation Across Sensory Modalities Task-Dependent?
AB  - Human information processing is limited by attentional resources. That is, via
      attentional mechanisms, humans select a limited amount of sensory input to
      process while other sensory input is neglected. In multisensory research, a
      matter of ongoing debate is whether there are distinct pools of attentional
      resources for each sensory modality or whether attentional resources are shared
      across sensory modalities. Recent studies have suggested that attentional
      resource allocation across sensory modalities is in part task-dependent. That is,
      the recruitment of attentional resources across the sensory modalities depends on
      whether processing involves object-based attention (e.g., the discrimination of
      stimulus attributes) or spatial attention (e.g., the localization of stimuli). In
      the present paper, we review findings in multisensory research related to this
      view. For the visual and auditory sensory modalities, findings suggest that
      distinct resources are recruited when humans perform object-based attention
      tasks, whereas for the visual and tactile sensory modalities, partially shared
      resources are recruited. If object-based attention tasks are time-critical,
      shared resources are recruited across the sensory modalities. When humans perform
      an object-based attention task in combination with a spatial attention task,
      partly shared resources are recruited across the sensory modalities as well.
      Conversely, for spatial attention tasks, attentional processing does consistently
      involve shared attentional resources for the sensory modalities. Generally,
      findings suggest that the attentional system flexibly allocates attentional
      resources depending on task demands. We propose that such flexibility reflects a
      large-scale optimization strategy that minimizes the brain's costly resource
      expenditures and simultaneously maximizes capability to process currently
      relevant information.

PMID- 28450976
TI  - Exploring Modality Compatibility in the Response-Effect Compatibility Paradigm.
AB  - According to ideomotor theory, action planning is based on anticipatory
      perceptual representations of action-effects. This aspect of action control has
      been investigated in studies using the response-effect compatibility (REC)
      paradigm, in which responses have been shown to be facilitated if ensuing
      perceptual effects share codes with the response based on dimensional overlap
      (i.e., REC). Additionally, according to the notion of ideomotor compatibility,
      certain response-effect (R-E) mappings will be stronger than others because some
      response features resemble the anticipated sensory response effects more strongly
      than others (e.g., since vocal responses usually produce auditory effects, an
      auditory stimulus should be anticipated in a stronger manner following vocal
      responses rather than following manual responses). Yet, systematic research on
      this matter is lacking. In the present study, two REC experiments aimed to
      explore the influence of R-E modality mappings. In Experiment 1, vocal number
      word responses produced visual effects on the screen (digits vs. number words;
      i.e., visual-symbolic vs. visual-verbal effect codes). The REC effect was only
      marginally larger for visual-verbal than for visual-symbolic effects. Using
      verbal effect codes in Experiment 2, we found that the REC effect was larger with
      auditory-verbal R-E mapping than with visual-verbal R-E mapping. Overall, the
      findings support the hypothesis of a role of R-E modality mappings in REC
      effects, suggesting both further evidence for ideomotor accounts as well as code
      specific and modality-specific contributions to effect anticipation.

PMID- 28450977
TI  - Empathy in Negative and Positive Interpersonal Interactions. What is the
      Relationship Between Central (EEG, fNIRS) and Peripheral (Autonomic)
      Neurophysiological Responses?
AB  - Emotional empathy is crucial to understand how we respond to interpersonal
      positive or negative situations. In the present research, we aim at identifying
      the neural networks and the autonomic responsiveness underlying the human ability
      to perceive and empathize with others' emotions when positive (cooperative) or
      negative (uncooperative) interactions are observed. A multimethodological
      approach was adopted to elucidate the reciprocal interplay of autonomic
      (peripheral) and central (cortical) activities in empathic behavior.
      Electroencephalography (EEG, frequency band analysis) and hemodynamic (functional
      Near-Infrared Spectroscopy, fNIRS) activity were all recorded simultaneously with
      systemic skin conductance response (SCR) and heart rate (HR) measurements as
      potential biological markers of emotional empathy. Subjects were required to
      empathize in interpersonal interactions. As shown by fNIRS/EEG measures, negative
      situations elicited increased brain responses within the right prefrontal cortex
      (PFC), whereas positive situations elicited greater responses within the left
      PFC. Therefore, a relevant lateralization effect was induced by the specific
      valence (mainly for negative conditions) of the emotional interactions. Also, SCR
      was modulated by positive/negative conditions. Finally, EEG activity (mainly low
      frequency theta and delta bands) intrinsically correlated with the cortical
      hemodynamic responsiveness, and they both predicted autonomic activity. The
      integrated central and autonomic measures better elucidated the significance of
      empathic behavior in interpersonal interactions.

PMID- 28450978
TI  - Beyond Low Rank + Sparse: Multi-scale Low Rank Matrix Decomposition.
AB  - We present a natural generalization of the recent low rank + sparse matrix
      decomposition and consider the decomposition of matrices into components of
      multiple scales. Such decomposition is well motivated in practice as data
      matrices often exhibit local correlations in multiple scales. Concretely, we
      propose a multi-scale low rank modeling that represents a data matrix as a sum of
      block-wise low rank matrices with increasing scales of block sizes. We then
      consider the inverse problem of decomposing the data matrix into its multi-scale
      low rank components and approach the problem via a convex formulation.
      Theoretically, we show that under various incoherence conditions, the convex
      program recovers the multi-scale low rank components either exactly or
      approximately. Practically, we provide guidance on selecting the regularization
      parameters and incorporate cycle spinning to reduce blocking artifacts.
      Experimentally, we show that the multi-scale low rank decomposition provides a
      more intuitive decomposition than conventional low rank methods and demonstrate
      its effectiveness in four applications, including illumination normalization for
      face images, motion separation for surveillance videos, multi-scale modeling of
      the dynamic contrast enhanced magnetic resonance imaging and collaborative
      filtering exploiting age information.

PMID- 28450979
TI  - Hydraulic Robotic Surgical Tool Changing Manipulator.
AB  - Natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique
      to perform "scarless" abdominal operations. Robotic technology has been exploited
      to improve NOTES and circumvent its limitations. Lack of a multitasking platform
      is a major limitation. Manual tool exchange can be time consuming and may lead to
      complications such as bleeding. Previous multifunctional manipulator designs use
      electric motors. These designs are bulky, slow, and expensive. This paper
      presents design, prototyping, and testing of a hydraulic robotic tool changing
      manipulator. The manipulator is small, fast, low-cost, and capable of carrying
      four different types of laparoscopic instruments.

PMID- 28450980
TI  - [Case report: a covered perforation in the duodenum by fish bone].

PMID- 28450982
TI  - [Cervical pregnancy at 7 weeks of amenorrhea: challenges of patient management].

PMID- 28450981
TI  - [Fahr syndrome secondary to primary hypoparathyroidism: about a case].
AB  - Fahr syndrome is a rare anatomo-clinic disease whose most common cause is primary
      or postoperative hypoparathyroidism. It is characterized by bilateral and
      symmetrical intracerebral calcifications located in the central gray nuclei, most
      often associated with phosphocalcium metabolism disorders. We here report the
      case of a 54-year old patient who had been treated for primary hypoparathyroidism
      for 20 years, presenting with amnesic disorders revealing Fahr syndrome secondary
      to hypoparathyroidism.

PMID- 28450983
TI  - [Accessory lobe of placental: Vasa previa should be suspected].

PMID- 28450984
TI  - A rare complication of catherer insertion pericardiocentesis.

PMID- 28450985
TI  - [Necrotizing fasciitis:a life-threatening condition!]

PMID- 28450986
TI  - [Major sickle cell syndromes and infections associated with this condition in
      children in Burkina Faso].
AB  - INTRODUCTION: This study aims to investigate infections in children with major
      sickle cell syndrome. METHODS: We conducted a monocentric descriptive
      retrospective hospital study in Ouagadougou, Burkina Faso, over a ten-year
      period. All children with major sickle cell syndrome (homozygous SS and double
      heterozygous SC, SDPunjab, Sbeta thalassemic, SOArab and SE) hospitalized for
      microbiologically confirmed infections were enrolled in the study. RESULTS: One
      hundred and thirty-three patients met our inclusion criteria. The SS phenotype
      accounted for 63.2% of cases and SC 36.8%. The frequency of infections was 21.8%.
      In 45.9% of cases, these affected children aged 0-5 years. The most frequent
      signs were osteoarticular pain (42.1%), cough (25.7%), abdominal pain (23.3%),
      pallor (43.6%). The major diagnoses were bronchopneumonia (31.6%), malaria
      (16.5%), osteomyelitis (12.8%) and septicemia (10.5%). The isolated pathogenic
      organisms were Streptococcus pneumoniae (35.5%) and Salmonella spp (33.3%). Third
      generation cephalosporins were the most commonly prescribed antibiotics. Gros
      mortality rate was 7.5%. CONCLUSION: Bacterial infections and malaria dominate
      the clinical picture of infections in children with major sickle cell syndrome at
      the at the Pediatrics University Hospital Center Charles De-Gaulle. This study
      highlights the importance of establishing a national program for the management
      of sickle-cell anemia, which could help prevent or reduce the occurrence of
      infections in children with sickle cell syndrome.

PMID- 28450987
TI  - [A rare cause of spontaneous hemoperitoneum in adults: ruptured cystic
      hemolymphangioma].
AB  - Hemolymphangioma is a benign tumor resulting from the abnormal development of the
      lymphatic vessels associated with vascular malformations. 50% to 60% of these
      tumours are present at birth. Cervical forms are most frequent. Abdominales
      locations are very rare. We report, through a literature review, two cases of
      patients with cystic hemolymphangioma of the spleen revealed by spontaneous
      haemoperitoneum admitted to the Emergency Department of Visceral Surgery. The
      first case is a 50-year old patient and the second is 20-year old man admitted to
      the emergency department with diffuse abdominal pain associated with dullness to
      percussion on the dependent side and abdominal distension associated with
      haemorrhagic shock, pallor, unobtainable pulse, stabilized after a short
      resuscitation time respectively. All patients underwent complete tumor resection.
      The diagnosis of cystic hemolymphangioma of the spleen was based on
      anatomopathological examination of the surgical specimens. Hemolymphangioma is a
      rare tumor with a favorable prognosis. Some cases of spontaneous regression have
      been reported, but evolution is usually characterized by slow tumor growth.
      Malignant transformation never occurs. Treatment is surgical. Prognosis is
      subjected to complications, quality of the surgical excision and recurrences
      which are frequent especially after incomplete excision.

PMID- 28450988
TI  - Laryngeal lipoma: a rare cause of dysphonia.
AB  - Lipomas are the most common mesenchymal tumors. Laryngeal lipomas represent 1% of
      all lipomas but unlike other locations may cause life-threatening symptoms by
      obstruction of the respiratory tract. In this study, the case of a 32-year old
      woman with laryngeal lipoma is discussed. The lesion was detected on the left
      aryepiglottic fold, presented as a stalked and dynamic mass of 2 centimeters
      diameter. The imaging aspects of laryngeal lipoma cases, clinical evaluation, and
      approaches to treatment will be discussed.

PMID- 28450989
TI  - [Etiological profile of anemia in a department of internal medicine].
AB  - Anemia is a major public health problem worldwide despite remarkable improvement
      in living conditions. The World Health Organization (WHO) classifies it as one of
      the ten most serious problems in the world. This study aims to describe the
      epidemiologic and etiologic profiles of the cases of anemia treated during our
      training. We conducted a retrospective study involving 150 patients carried out
      over 5 years, from January 2011 to December 2015. The average age of our patients
      was 48.8 years and women were more likely to be affected than men, with a sex
      ratio of 1.78. The mean hemoglobin was 8 g/dl, ranging from 3.4 to 11.4 g/dl.
      Iron deficiency anemia was the leading etiologic diagnosis made in 60% of cases,
      followed by megaloblastic anemia in 21% of patients and haemolytic anemia in
      7.33% of cases. The occurrence of anemia in adults may represent a real
      diagnostic challenge for the internist as it is sometimes associated with an
      emergency context. Specialized examinations may be necessary.

PMID- 28450990
TI  - [Anatomopathological profile of breast cancer in cape bon, Tunisia].
AB  - Breast cancer is the most common cancer among tunisian women and worldwide. In
      Cape Bon, Tunisia, the anatomopathological features of this cancer have not been
      established in previously published studies. Knowledge about these features is
      needed for the cultural adaptation of prevention and health care systems in the
      region. The aim of our study was to determine the pathological profile of breast
      cancers in the only public health anatomic pathology regional laboratory. We
      conducted a retrospective descriptive study of 116 patients who were diagnosed
      with breast cancers in our laboratory over a 5-year period, from July 2010 to
      July 2015. Our study included 116 patients. The average age was 51 years. The
      mean histologic tumor size was 31 mm. The initial diagnosis was based on
      lumpectomy in 83% of the cases. Nonspecific invasive cancer was the most frequent
      histological type. SBR grade III was most prevalent. Lymphovascular invasion was
      detected in 33% of cases. Axillary lymph node dissection was performed in 72% of
      cases. Hormone receptors were positive in 73% of cases. Her2-Neu receptors were
      overexpressed in 19% of cases. The ki67 was >= 14% in 38% of cases. Luminal A was
      the most common molecular subtype. In Cap Bon region brest cancer is
      characterized by an early onset, a large tumor size and pejorative
      histoprognostic factors.

PMID- 28450991
TI  - [Poland syndrome: about a case and review of the literature].
AB  - Poland syndrome is a rare congenital malformation associated with various degrees
      of thoracic and homolateral upper limb abnormalities. We report the case of a 7
      year old girl who underwent exploration for depression of the left hemithorax
      associated with homolateral subclavicular mass. CT scan showed that the
      deformation of the thoracic wall was related to the absence of left pectoralis
      major muscle sterno-costal heads insertion associated with agenesis of the
      pectoralis minor muscle and hypoplasia of the anterior arches of the first six
      corresponding ribs. These abnormalities were related to Poland syndrome. General
      assessment was based on abdominal ultrasound, X-rays of both hands and did not
      show any associated malformation. Poland syndrome results from a deficit of blood
      flow to musculoskeletal elements of the chest wall during fetal life. There are
      many variants of Poland syndrome that can be best detected by CT scan and which
      must be performed whenever necessary, without omitting the role of general
      radiology in the detection of associated malformations. This syndrome is
      characterized by the agenesis of the sternocostal bundles of the pectoralis major
      muscle. Its etiology remains unknown and discussed. It can be caused by a
      vascular anomaly, without the primum movens of this vascular anomaly being known.

PMID- 28450992
TI  - [Study of the bacteriological quality of water used in the agro-food industry in
      the North of Morocco].
AB  - INTRODUCTION: Water is used predominantly in food manufacturing process. Northern
      morocco agro-food industries use different sources of water, but public water and
      wells water are the main sources of water used. This water can be the main source
      of possible food contaminations and alterations. This study aims is to assess the
      bacteriological quality of water used in the agro-food industries in the Northern
      region of Morocco, to identify the different types of germs responsible for the
      pollution of these waters and to establish the main causes of this pollution.
      METHODS: Water samples taken from taps or wells were analyzed to detect pollution
      indicator germs (total coliform (TC), fecal coliform (FC), intestinal enterococci
      (E), revivable microorganisms (RM), sulphite-reducing anaerobes) and pathogens
      (Salmonella, Staphylococci, Pseudomonas aeruginosa). The enumeration of the
      bacteria was performed by filtration technique and incorporation obtained through
      supercooled solid state. RESULTS: The results showed that public-supply waters
      were of satisfactory bacteriological quality while 40% of the wells water was non
      compliant with water quality standards due to the presence of TC, FC, E and RM
      pollution indicators. In contrast, pathogens, particularly Salmonellae, were
      absent in all the wells water analyzed. CONCLUSION: Well water pollution was
      generally due to failure to meet hygienic requirements for water pumping.
      Bacteriological quality of these wells water could be improved by adequate
      protection.

PMID- 28450993
TI  - CD4+ cells recovery in HIV positive patients with severe immunosuppression at
      HAART initiation at Centre Medico-Social Cor-Unum, Kigali.
AB  - INTRODUCTION: Up to 30% of HIV infected patients who are receiving HAART do not
      exhibit a marked increase in the CD4+ T cell count. There is still a concern that
      immune recovery may not be complete once CD4+ T cells have decreased below 200
      cells/MUl. The objective is to assess CD4+ cell recovery in HIV+ patients with
      CD4 count below 200 cells/MUl) at HAART initiation. METHODS: This was a
      retrospective cohort study among 110 HIV+ patients with initial CD4 count < 200
      cells/MUl. Baseline Age, sex, CD4 count and viral load were extracted from the
      patient's database. After12 months of HAART; CD4 count was done using flow
      cytometry and viremia by COBAS AmpliPrep/COBAS TaqMan HIV-1 test v 2.0
      technology. RESULTS: The mean age of the respondents was 35 years; males being
      57% and females were 43%. The mean CD4 count before HAART was 110.18 cells/MUl
      whereas at 12 months of HAART; this was 305.01 cells/MUl. Though some patients
      did not achieve a CD4 count of more than 200 cells/MUl or a drop in viral load;
      there was a significant recovery of CD4+ cells (P value=0.000) and viremia
      following HAART (P value=0.001). Participants aged 18-30 years were likely to
      have less than 200 cells/MUl CD4 count (46.4%) [OR=4.33; 95%CI: 1.29-14.59;
      P=0.018] than participants aged above 40 years (16.7%). CONCLUSION: HAART was
      associated with viremia suppression but many patients failed to achieve a CD4
      count >200 cells/MUl. HAART before severe immunosuppression is a key factor for
      immune restoration among HIV+ patients.

PMID- 28450994
TI  - [Student abuse and Graves-basedow's disease: about a case].
AB  - Graves-basedow's disease is an autoimmune thyreopathy which represents the most
      common cause of hyperthyroidism in both adults and children. This disease would
      be related to a genetic predisposition influenced by environmental triggers,
      including stress. This study aims to present a case of Graves' disease in
      children whose unusual trigger would be student abuse, a broad challenge with
      multiple implications.

PMID- 28450995
TI  - [Epidemiological aspects of spinal traumas: about 139 cases].
AB  - Spinal trauma is one of the most common types of injuries among victims of
      traffic accidents, sports accidents, domestic accidents and workplace accidents.
      We conducted a 3-year retrospective study of 139 cases of spinal trauma
      hospitalized and treated in the Neurosurgery department of the CHUJRA,
      Madagascar. This study shows that 25.17% of injured patients were between 21 and
      30 years of age, with a clear male predominance (69.78%; sex ratio 2.3). Falls
      were the dominating traumatic injury mechanism (33.09%) with risk factors
      including alcohol use (8.63%). Spinal injuries occurred in patients with
      polytrauma, of whom 34.63% had cranial trauma. Patients were admitted to the
      department within 1-5 hours after the trauma in 31.65% of cases, using private
      car as their means of transport 36.69% of cases. During the hospitalization 20
      patients signed the discharge form and 6.34% of patients died. Spinal trauma is a
      public health problem requiring high intensity management, especially for
      patients with life-long disabilities. Any spine trauma requires a diligent search
      for cranial lesion.

PMID- 28450996
TI  - A clinical correlation between stature and posterior tooth length.
AB  - INTRODUCTION: Exploration and determination of the relationship between stature
      and length of tooth is essential in Paleontology, Forensic Odontology and
      Endodontology. This study aimed to determine any association between stature and
      posterior tooth length in a group of patients who required root canal treatment.
      METHODS: Age, sex and standing height of adults were considered for posterior
      tooth length measurement. Molars and Premolars of apparently normal males (n=115
      for molars, n= 75 for premolars) and females (n=124 for molars, n=80 for
      premolars), aged 20-50 years with intact cuspal morphology, which required RCT
      were selected for this study. Females and males were divided into 2 groups each
      based on their heights females > 155 cm and <= 155 cm, males > 165.10 and <=
      165.10cm. The tooth length of permanent molars and premolars in both groups were
      measured using RVG and Electronic apex locator. Measurements obtained were
      compared separately for males and females using descriptive statistics and
      Pearson correlation coefficient. RESULTS: In females MB, ML, D roots of molar
      showed significant association (P=0.021), (P=0.027), (P=0.010) and roots of
      premolars showed significant association (P=0.002), (P=0.006) between both the
      groups respectively In males MB, ML, D roots of molar showed significant
      association (P=0.009), (P=0.004), (P=0.015) and roots of premolars showed
      significant association (P=0.006), (P=0.020) between both the groups
      respectively. CONCLUSION: The present clinical study reveals that there is a
      positive association between stature and posterior tooth length in both males and
      females.

PMID- 28450997
TI  - [Iatrogenic common carotid artery injury secondary to an internal jugular venous
      catheterization].
AB  - Carotid injury occurring during venous jugular catheterization is a rare but
      potentially dramatic event. We report a case of compressive cervical hematoma
      associated with haemothorax occurred after common carotid artery injury during
      internal jugular venous catheterization. The diagnosis and management of this
      type of complication are discussed.

PMID- 28450998
TI  - [A rare case report of laryngeal leech infestation in a 70-year-old man].
AB  - Foreign bodies in the upper respiratory tract are one of the most difficult
      otolaryngological emergencies; leeches are a very rare foreign bodies in the
      world. We report the case of a 70-year-old man with no past medical history
      presenting with laryngeal dyspnea associated with low abundant paroxysmal
      hemoptysis. The patient underwent nasofibroscopy showing the presence of a living
      and mobile organism at the subglottic level evoking a leech. Extraction was
      carried out under local anesthesia using laryngoscope and Magill forceps. The
      presence of a leech as a foreign body in the upper respiratory tract should be
      suspected in patients with a recent history of consumption of non-potable water.

PMID- 28450999
TI  - [Ectopic thyroid: the role of thyroid scan].
AB  - Ectopic thyroid is a rare malformative disease. We report an additional case of
      ectopic right thyroid lobe, detected during CT scan evaluation of a left lateral
      cervical mass.

PMID- 28451000
TI  - Prevalence and risk factors of workplace violence against health care workers in
      emergency department in Ismailia, Egypt.
AB  - INTRODUCTION: Emergency department is one of the high-risk areas, where violence
      against health care workers (HCWs) is a prevalent and serious problem. Violence
      has negative effects on HCWs, and therefore on the quality of care provided in
      emergency department. This study aimed to determine the prevalence, types,
      sources and risk factors of violence reported by HCWs in emergency department.
      METHODS: A cross-sectional study was conducted using a standardized questionnaire
      developed by the WHO. One hundred thirty four questionnaires were included in
      this study (94.4% response rate). RESULTS: WPV was reported by 59.7% of HCWs.
      Verbal violence was the most reported (58.2%), compared to physical violence
      (15.7%). The most reported reasons for violence were waiting time and that
      patient and family expectations not being met. Only 29.5% of HCWs who experienced
      verbal violence and 23.8% of who experienced physical violence reported it to
      hospital authority. About 75% of HCW thought that work place violence could be
      prevented, and about 60% said that no action was taken against the attacker by
      hospital authority. CONCLUSION: Violence against HCWs in emergency department is
      a significant issue that cannot be ignored. There are multiple reasons. The key
      point in dealing with the problem is to treat its specific causes.

PMID- 28451001
TI  - [Management of airway and cervical facial cellulitis].

PMID- 28451002
TI  - [Costal metastasis revealing esophageal squamous cell carcinoma].
AB  - Esophageal cancer is associated with poor prognosis. Its severity is linked to
      delayed diagnosis which is most often made once a cancer has metastasized, in
      Africa. Costal metastases are rare. We report a case of a 38-year old Senegalese
      patient with squamous cell carcinoma of the lower esophagus with lytic metastases
      to the ribs. Mrs. TD, aged 38, was admitted with painful swelling in right
      hemithorax associated with weight loss. The patient also reported mechanical
      dysphagia evolving during 4 months which had not motivated consultation. Clinical
      examination showed a poor general condition, a hard, sensitive swelling measuring
      3 cm along its longer axis, located on the anterolateral surface of the right
      hemithorax at the level of the 5thrib. Biological examinations showed normocytic
      normochromic anemia with hemoglobin level of 9.4 g/dl, non-specific biological
      inflammatory syndrome, and hypercalcemia (corrected calcium = 107 mg/l.
      Oesogastroduodenal endoscopy showed a ulcerative, budding, stenotic lesion 32 cm
      from the dental arches. Anatomopathological examination of the biopsies revealed
      moderately differentiated squamous cell carcinoma. In addition to oesophageal
      tumor, thoracoabdominal-pelvic computed tomography showed bone lysis involving
      the anterior arch of the 5th rib, carcinomatous pulmonary nodules and bilateral
      pleural effusion. Pleural fluid aspiration through an exploratory needle showed
      serohematic fluid and the cytological examination of this fluid objectified
      carcinomatous cells. The diagnosis of squamous cell carcinoma of the lower
      esophagus with rib, pleural and pulmonary metastases was retained and palliative
      treatment was initiated. The evolution was marked by the death of the patient 3
      months after gastrostomy, within a context of respiratory distress. The
      originality of this observation is related to the atypical seat of metastases of
      this cancer of the esophagus as well as the risk factors of this tumor. Cancer of
      the esophagus in young adults is a major problem in Africa. The challenge is to
      determine its risk factors in order to prevent its occurrence.

PMID- 28451003
TI  - [A rare tumor of the thigh].

PMID- 28451005
TI  - [Leiomyosarcoma of the urinary bladder treated using laparoscopic cystectomy and
      bladder replacement by enterocystoplasty: about a case].
AB  - Our study aims to report a new case of leiomyosarcoma of the urinary bladder, a
      rare tumor, and to propose a new therapeutic approach, given the non-consensual
      nature of its treatment. A 31-year old patient, with no particular previous
      history, presented with total haematuria with clot formation. The clinical and
      paraclinical assessment showed a voluminous solid tumor mass occupying the apex
      of urinary bladder and extending to the right lateral wall, with infiltrating
      appearance, without lymph node involvement or invasion of local or distal organs.
      Surgical management was based on total laparoscopic cystectomy and bladder
      replacement by enterocystoplasty. The postoperative course was uneventful.
      Radiological examinations at 3, 6, 12 and 24 months showed no recurrence. Thus,
      adaptive surgery should be proposed on a case-by-case basis, to improve the
      quality of life of patients suffering from this condition.

PMID- 28451004
TI  - [Thymic neuroendocrine tumor: about a case and review of the literature].
AB  - Thymic neuroendocrine tumors (TNET) are rare, with little-known prognosis. This
      study aims to report a case of TNET and to highlight the diagnostic and
      therapeutic difficulties in low-resource settings. A 60-year-old man presented
      with chest pain, greasy cough and recent weight loss. Chest CT scan showed
      anterior mediastinal tissue mass. Histologic evaluation of a 4 months-biopsy
      specimen obtained from anterior mediastinotomy showed a well differentiated TNET,
      labeled intensely positive for chromogranin and synaptophysin. The search for
      other neuroendocrine tumors and the extent of extension were negative. The tumor
      was immediately inextricable and radiation therapy was unavailable. The patient
      underwent two lines of first line chemotherapy. At 16 months follow-up, the
      patient was asymptomatic but showed tumor progression. The diagnosis of TNET may
      be delayed when immunohistochemistry is not routinely performed. Chemotherapy is
      associated with symptoms improvement in palliative care situation.

PMID- 28451006
TI  - [Nasosinusal polyposis revealing maxillary sinus mucocele].

PMID- 28451007
TI  - [Vesicular carcinoma in lingual thyroid: a rare case].
AB  - Lingual thyroid is secondary to the absence of migration of the thyroid
      diverticulum. The latter develops locally, that is, at the level of the foramen
      caecum. It may be the only thyroid tissue present, or it may be associated with a
      normal thyroid. The occurrence of a lingual thyroid carcinoma is rare accounting
      for about thirty cases described in the literature. This study reports a case of
      vesicular carcinoma in lingual thyroid.

PMID- 28451008
TI  - ?

PMID- 28451009
TI  - [Pityriasis versicolor in infants: unusual clinical presentation and role of
      corticosteroids used as depigmenting agent for cosmetic purposes in the mother].
AB  - We report two cases of Pityriasis versicolor (PV) in infants aged 12 and 18
      months. The latter were brought to medical attention because of hypochromic and
      achromic, round macules involving the limbs and the face. Physical examination of
      their mothers showed voluntary depigmentation for cosmetic purposes due to the
      use of corticosteroids and hydroquinone, on average, over a 5-year period. The
      scotch tape test performed in one of the infants and his mother showed short
      filaments and clusters of spores. Treatment was based on ketoconazole. After 8
      weeks, all patients reported favorable outcomes despite the persistence of some
      hypochomic macules. The peculiarities of this study are, on the one hand the
      topography of the lower limbs and on the other hand a positive family history of
      PV whose occurrence is favored by the use of depigmenting agents based on
      corticosteroids. Corticosteroids favor the atrophic and achromic feature of the
      lesions. Indeed, achromic lesions on the lower limbs were described in adults
      undergoing artificial depigmentation.

PMID- 28451011
TI  - Cystic lymphangioma in a 44-year-old woman.

PMID- 28451010
TI  - [Acquired amegacaryocytic thrombocytopenic purpura hiding acute myeloid
      leukemia].
AB  - Acquired amegakaryocytic thrombocytopenic purpura is a very rare condition
      characterized by severe thrombocytopenia linked to the reduction or disappearance
      of megakaryocytes in the bone marrow. It may be primary idiopathic or secondary
      to many pathological conditions including hematologic disorders. We report the
      case of a 24-year-old patient admitted for haemorrhagic syndrome caused by
      immunological thrombocytopenic purpura. The diagnosis was acquired
      amegakaryocytosis after the failure of corticotherapy and the performance of
      myelography. The patient was treated with ciclosporin with rapid progression to
      acute myeloblastic leukemia. The progression of acquired amegakaryocytosis to
      acute leukemia is reported but it is generally not so rapid and above all it is
      preceded by myelodysplastic syndrome or medullary aplasia. This study highlights
      the importance of a close follow-up of these pathologies with a benign-like
      appearance.

PMID- 28451012
TI  - [Pyoderma gangrenosum of the scalp: about a case].

PMID- 28451013
TI  - The effect of group exercise frequency on health related quality of life in
      institutionalized elderly.
AB  - INTRODUCTION: The study aimed to determine the effect of group exercise frequency
      on health related quality of life in institutionalized elderly. METHODS: One
      hundred participants were recruited for voluntary participation from five aged
      care facilities, with inclusion being based on the outcome of a medical
      assessment by a sports physician. A quasi-experimental design was used to compare
      the effect of a 12 week group exercise programme on two groups of participants
      using pre-test and post-test procedures. RESULTS: A significant difference was
      noted in social function post training 2X/week (MD = -13.85, 95% CI [-24.66, 
      3.38], p = 0.017, d = 0.674) and 3X/week (MD = -13.30, 95% CI [-21.81, -5.59], p
      = 0.003, d = 0.712) a week. Training 3X/week a week provided an additional
      benefit in vitality (MD = -7.55, 95% CI [-13.16, -1.91], p = 0.018, d =0. 379).
      Improvements in mental component summary scale post training 2X/week (MD = -4.08,
      95% CI [-7.67, -0.42], p = 0.033, d = 0.425) and 3X/week (MD = -6.67, 95% CI [
      10.92, -2.33], p = 0.005, d = 0.567) a week was further noted. CONCLUSION: Mental
      health and social health benefits can be obtained irrespective of exercise
      frequency 2X/week or 3X/week. The exercise intervention at a frequency 3X/ week
      was more effective in improving mental component summary due to a larger effect
      size obtained compared to the exercise frequency of 2X/week. Additional benefits
      in vitality were achieved by exercising 3X/week. This may assist the elderly in
      preserving their independence.

PMID- 28451014
TI  - Role of H-FABP values in determining the etiologic factors of the cardiac
      injuries.
AB  - INTRODUCTION: Cardiac injury resulting from blunt thoracic trauma is a frequent
      clinical occurrence which is difficult to diagnose. Our purpose in this study was
      to research whether H-FABP, which is a new marker for the diagnosis of cardiac
      injury, can be used in this patient group. METHODS: 50 patients with blunt
      thoracic injury who were admitted to our emergency service within a period of 8
      months and 50 cases as controls were included in our study. RESULTS: Of the 50
      patients with blunt thoracic injury in our study, 88% were male while 12% were
      female. The average age of the patients was 43 +/- 15.15. While 27 (54%) of the
      50 patients with blunt thoracic injury had cardiac injury, 23 (46%) did not have
      cardiac injury. The results of the statistical analyses showed a significant
      association between thorax trauma and cTnI, CPK, CPKMB and H-FABP (p<0.05). While
      there was a significant association between cardiac injury resulting from
      thoracic trauma and cTnI, ECG and TTE (p<0.05), there was no significant
      association between CPK, CPKMB and H-FABP (p>0.05). CONCLUSION: In thoracic
      traumas, cardiac injury diagnosis can be made as a result of the assessment with
      Troponin-I, ECG and ECHO. For cardiac injury diagnosis, wide scale prospective
      studies are needed for H-FABP use.

PMID- 28451015
TI  - Multilevel analysis of school anti-smoking education and current cigarette use
      among South African students.
AB  - INTRODUCTION: South Africa (SA) implemented the Global Youth Tobacco Survey
      (GYTS) four times between 1999 and 2011. Data from the four surveys indicated
      that downward trends in cigarette use among students may have stalled.
      Understanding the effect of school anti-smoking education on current smoking
      among students within schools and variability across schools may provide
      important insights into policies aimed at preventing or reducing tobacco use
      among students. The objective was to assess the student- and school-level effects
      of students' exposure to school anti-smoking education on current cigarette use
      among the study population using the most recent wave of GYTS data in SA (2011).
      METHODS: An analytic sample of students 13-15 years of age was selected (n=3,068)
      from the SA GYTS 2011. A taxonomy of two-level logistic regression models was fit
      to assess the relationship of various tobacco use, control, and exposure
      predictor variables on current cigarette smoking among the study population.
      RESULTS: At the student-level in the full model, secondhand smoke (SHS) exposure,
      peer smoking, and ownership of a promotional item were significantly associated
      with higher risk of current smoking. At the school-level in the full model,
      average exposure to peer smoking was associated with significant increases in the
      prevalence of current cigarette use, while average family anti-smoking education
      was significantly associated with decreases in the outcome variable. School anti
      smoking education was not a statistically significant predictor at the student-
      or school-levels. CONCLUSION: in this study, exposure to school anti-smoking
      education had no association with current cigarette smoking among the study
      population. Consistent with previous studies, having peers that smoked was highly
      associated with a student being a current smoker. Interestingly, at the school
      level in the multilevel analysis, schools with higher rates of average family
      anti-smoking education had lower prevalence of current smoking. This finding has
      potential implications for tobacco control in SA, particularly if the school
      level, family-centered protective effect can be operationalized as a prevention
      tool in the country's tobacco control program.

PMID- 28451017
TI  - [Knee monoarthritis revealing tabetic arthropathy].

PMID- 28451016
TI  - Prevalence and genetic diversity of rotavirus infection in children with acute
      gastroenteritis in a hospital setting, Nairobi Kenya in post vaccination era: a
      cross-sectional study.
AB  - INTRODUCTION: Rotavirus is the leading cause of severe diarrhoea among infants
      and young children. Each year more than 611 000 children die from rotavirus
      gastroenteritis, and two million are hospitalized, worldwide. In Kenya, the
      impact of recent rotavirus vaccinations on morbidities has not been estimated.
      The study aimed at determining the prevalence and identity of rotavirus strains
      isolated from rotavirus-associated diarrhoea in vaccinated children presenting
      with acute gastroenteritis. METHODS: Two hundred and ninety eight specimen from
      children presented at Gertrude Childrens' Hospital from January to June 2012 were
      tested by EIA (Enzyme-linked Immunosorbent Assay) for rotavirus antigens.
      Molecular characterization was conducted on rotavirus-positive specimens.
      Extracted viral RNA was separated by polyacrylamide gel electrophoresis (PAGE)
      and the specific rotavirus VP4 (P-types) and VP7 (G-types) determined. RESULTS:
      The prevalence rate of rotavirus was 31.5% (94/298). Of the rotavirus dsRNA, 57
      (60.1%) gave visible RNA profiles, 38 (40.4%) assigned long electropherotypes
      while 19 (20.2%) were short electropherotypes. The strains among the vaccinated
      were G3P [4], G12P [6], G3P [6], G9P [4], G mixed G9/3P [4] and G1/3P [4].
      Specifically, the G genotypes were G9/3 (5.3%), G9 (4.3%), G3 (4.3%), G12 (2.1%)
      and mixed G1/3 (1.1%). The P genotypes detected were P [4] (5.3%) and P [6]
      (5.3%). CONCLUSION: The present study demonstrates diversity in circulating
      genotypes with emergence of genotypes G3, G9, G12 and mixed genotypes G9/3 and
      recommends that vaccines should be formulated with a broad range of strains to
      include G9 and G12.

PMID- 28451018
TI  - Infective endocarditis in Principal Hospital of Dakar: a retrospective study of
      42 cases over 10 years.
AB  - Infective Endocarditis (IE) is an endocardial infection usually caused by
      bacteria that affects not only the native heart valves but also, with increasing
      frequency intravascular implanted devices and congenital heart diseases. Despite
      medical advances, IE remains a life-threatening disease with substantial
      morbidity and mortality. In Africa, its diagnosis and treatment are still a major
      challenge in clinical practice. The objective of this work was to study the
      epidemiological, clinical features, diagnostic techniques currently used in
      medical practice and the range of micro-organisms that are responsible. This was
      a retrospective study done at Principal Hospital of Dakar. We include all
      patients who were admitted with clinical manifestations of definite or possible
      IE according to the extended DUKE criteria between January 1st, 2005 and December
      31st, 2014. We collected and analyzed epidemiological, clinical, paraclinical and
      outcomes data of 42 patients. Hospital prevalence of IE was 0.078% (42/53711).
      The mean age was 27.5+/- 18 years with a sex ratio (M/F) of 0.55. IE were more
      common in patients with damaged or abnormal heart valves (78.6%) and in thoses
      with underlying structural defects (14.3%). The most common presenting symptoms
      were fever (90%) and cardiac murmurs (81%). Extracardiac clinical manifestations
      were very rare. The usual laboratory parameters of inflammation were elevated in
      90% of patients. Blood cultures were negative in 50% of cases and positive in
      21.4%. The main organism found was Staphylococcus aureus. Echocardiography found
      vegetations in 95.2% of cases, chamber enlargement in 73.8% and mitral
      regurgiation in 83.3%. Broad-spectrum penicillins including ampicillin and
      gentamycine were used for all patients. Major complications were heart failure
      (47.6%). Strokes and cerebral abcess (23.8%) and Vascular emboli 14.3%. Hospital
      mortality was 31%. IE remains a life-threatening disease with hight mortality
      despites improved techniques of diagnosis and modern antibiotics.

PMID- 28451019
TI  - Prevalence, aetiology and antibiotic sensitivity profile of asymptomatic
      bacteriuria isolates from pregnant women in selected antenatal clinic from
      Nairobi, Kenya.
AB  - INTRODUCTION: Asymptomatic bacteriuria (ASB) is the presence of bacteria in urine
      without apparent symptoms of urinary tract infections. The importance of
      asymptomatic bacteriuria lies in the insight it provides into symptomatic
      infections. To determine prevalence, bacterial isolates and Antibiotic
      Sensitivity Profile of asymptomatic bacterial urinary tract infection in pregnant
      women in selected clinics in Nairobi. METHODS: This was a cross-sectional study
      involving women attending antenatal clinic at selected clinics of Nairobi County.
      The women who met the inclusion criteria were included in the study. The
      midstream urine samples of these women were subjected to microscopy, culture and
      sensitivity. RESULTS: A total of 1020 of women on their first antenatal clinic
      visit participated in the study; 219 of them had ASB, giving a prevalence of 21.5
      % at 95% confidence level. Escherichia coli were the common organism isolated at
      38.8%. The majority of the organisms were sensitive to imipenem and gentamycin.
      CONCLUSION: There is a high prevalence of ASB among pregnant women included in
      the study from the Nairobi county clinics. Therefore, routine ASB screening of
      pregnant women is recommended among the women attending antennal clinics in
      Nairobi county clinics.

PMID- 28451020
TI  - Foramen magnum meningioma's management: the experience of the department of
      neurosurgery in Marrakesh.
AB  - Our study is a retrospective analysis of the clinical data, surgical outcomes,
      histological finding and prognosis of foramen magnum meningiomas through a serie
      of 8 cases operated at the department of neurosurgery at Mohammed VI medical
      university hospital, Marrakesh. From January 2002 to December 2015. There were 3
      male and 5 female patients (mean age, 46.75 years). Cervico-occipital pain (100%)
      and motor deficit (100%) were the most common presenting symptoms. MRI was the
      most appropriate diagnostic tool in visualizing tumors of this region. All
      operations were performed by the posterior approach and gross total resection was
      achieved in 7 cases. Surgical mortality was 20%. 3 other patients had
      complications like CSF leak (25%), meningitis (12,5%) and transient worsening of
      neurological deficit (12.5%) but made neurological recovery later. Foramen magnum
      meningiomas have long been regarded as difficult lesions both in terms of
      diagnosis and management. However, with the availability of MR imaging, newer
      surgical techniques and skull base exposures, the excision of these lesions is
      becoming easier and safer.

PMID- 28451021
TI  - Depression among HIV/AIDS Sudanese patients: a cross-sectional analytic study.
AB  - INTRODUCTION: Depression and HIV/AIDS are common morbid health problems; the
      relationship is bidirectional exacerbating each other with deleterious
      consequences. There are limited studies on this topic in Sudan. In this study, we
      investigated depression among HIV/AIDS in Sudan. METHODS: A cross-sectional
      analytic study was conducted among 362 HIV/AIDS patients from three centers in
      Khartoum, Sudan. Data were collected by the Hospital Depression and Anxiety
      (HADS) questionnaire. Chi-square was used for testing the significance and a P.
      Value of >= 0.05 was considered as statistically significant. RESULTS: Depression
      was evident in 332 (63.1%) of patients 68 (19.3%) had mild depression, 114
      (32.4%) moderate depression, and 40 (11.4%) severe depression. Depression was
      commoner among women, illiterate, married/widowed, not receiving counseling,
      delaying the result of the test, P-value <0.05, no significant differences were
      found regarding test and treatment type P- Value >0.05. CONCLUSION: Depression
      was prevalent among HIV/AIDS patients, especially females, low level of
      education, and widowed/married patients, and those not receiving counseling and
      post diagnosis sessions.

PMID- 28451023
TI  - [Prevalence of smoking among doctors and paramedical staff in Hospital University
      Center Mohammed VI, Marrakech].
AB  - Smoking is a major public health problem. Doctors and paramedical staff are not
      excluded from this plague. Smoking ban in hospitals originated from government
      effort to reduce passive smoking. The objectives were to evaluate smoking habits
      among doctors and paramedical staff in order to implement tobacco control
      strategy in this study population and to refer them to the smoking-cessation
      counselling. We conducted a descriptive cross-sectional study of the entire staff
      of the Hospital University Center Mohammed VI, Marrakech based on the
      distribution of anonymous questionnaires. A total of 530 questionnaires were
      distributed, and 380 were returned, a response rate of 71.7%. The study
      population consisted of 58.2% women (n=221) and 41.8% men (n=159). Doctors
      (n=220) were the most represented occupational category (57.9%) followed by
      nurses (31.8%). Smokers (n=62) accounted for 16.3% of our study population; the
      ex-smokers (n=31) accounted for 8.1% and the non-smokers (n=287) 75.5%. The
      average age of smokers was 31.1 years, ranging from 22 to 56 years. The
      prevalence of smoking was 16.3% (n=62) of study population, of whom 32.7% (n=52)
      among men compared to 4.5% (n=10) among women. The average age of smoking onset
      was 19 years with a range from 11 to 29 years and with a mean consumption of 9
      cigarettes/day. 13% (n=50) of people even smoked narguile, 9% (n=34) consumed
      alcohol, and 3% (n=21) cannabis. 67.7% of smokers (n=42) were planning to quit,
      of whom 30.9% (n=13) in the next 3 months, 52.4% (n=22) in the next 6 months and
      16, 7% (n=16) were planning to quit in the year. Several activities encouraged
      smoking, including night shift, coffee breaks and meals in 90.3% (n=56), 64.3%
      (n=40) and 61.3% (n=38) of cases respectively. This survey highlights the need to
      carry out awareness-raising actions to strengthen people motivation to quit
      smoking and help them during their withdrawal.

PMID- 28451022
TI  - [Pleuropulmonary metastases originating from extra-thoracic neoplasia].
AB  - The lungs receive the entire venous drainage of the body. This explains the high
      incidence of pleuropulmonary metastases originating from several cancers. The
      goal of this is to study the clinical manifestations of pleuro-pulmonary
      metastases originating from extra-thoracic cancers. We conducted a retrospective
      study of patients with pleuro-pulmonary metastasis whose data were collected in
      our department between January 2006 and december 2014. 76 patient medical records
      were studied. The average age was 50 years (aged 21-89 years) with a male
      predominance in 57.8% of cases. Clinical symptoms were mainly cough (32.8% of
      cases), dyspnea (23.7% of cases) and hemoptysis (11.2%). Primary cancers
      responsible for various pleuro-pulmonary metastases found in our case series were
      dominated by breast cancers in 27.6% of cases, gastro-intestinal cancers in 15.8%
      of cases, genital cancers in 9, 2% of cases, sarcomas in 7.8% of cases, renal
      cancers in 5.2% of cases, bladder cancers in 5.2% of cases, prostate cancers in
      3.9% cases, ENT cancers in 3.9% of cases, thyroid cancers in 3.9% of cases, skin
      cancers in 2.6% of cases and cancers of unknown primary origin in 14.4% of cases
      respectively. Several radiologic features of pleuro-pulmonary metastases have
      been found in our case series; they can be isolated or combined. The most common
      radiologic aspect was multiple pulmonary nodules in 52.6% of cases, followed by
      pleurisies in 34.2% of cases, diffuse micronodules in 23.6% of cases and a
      solitary nodule in 3.94% of cases. Secondary pleuropulmonary cancers are
      frequent. They come in 3rd place after lymph nodes and liver metastases and are
      found in 30% of autopsies of patients with neoplasia.

PMID- 28451024
TI  - [Distal hypoperfusion ischemic syndrome complicating a humeral-cephalic
      arteriovenous fistula].

PMID- 28451025
TI  - [Asteroid hyalopathy (benson's disease): about a case].
AB  - We here report a case of a 58 year-old diabetic male patient with asteroid
      hyalopathy, an affection rarely described in the literature. This study can help
      focus the attention of scientists on the pathologies of the vitreous disorders in
      diabetic patients as well as on other systemic diseases asteroid hyalopathy may
      be associated with.

PMID- 28451026
TI  - National strategy for the integration of pharmacovigilance in the Moroccan TB
      Control Program.
AB  - The objective of this work is to demonstrate the interest of integration of
      pharmacovigilance in Moroccan Tuberculosis Control Program (MTCP). The
      integration of pharmacovigilance in MTCP was conducted in October 2012with the
      Global Fund support. We compared the reports notified before and after this
      integration (period 1: January 2010-October2012; period 2: October 2012-December
      2013). The detection of signals was based on the Information Component available
      inVigiMine. We used the SPSS version 10.0 and Med Calc version 7.3 for data
      analysis. The average number of spontaneous reports increased from 3.6 to 37.4
      cases/month (P< 10-3). The average age was 40.7 +/- 17.5 years; the sex ratio was
      0.8. Hepatic reactions (32.7%) predominated during the first period, while skin
      reactions (24.1%) were in the second period (P = 10-4), and40.9% of cases in the
      first period were serious against 15.8% in second period (P = 0.003). Nine
      signals were generated (hepaticenzyme increase, cholestasis, jaundice,
      arthralgia, acne, lower limb edema, pruritus, skin rashes, and vomiting). The
      integration of pharmacovigilance in Moroccan Tuberculosis Control Program
      improved the management of ADRs and detected new signals of antituberculosis
      drugs.

PMID- 28451027
TI  - Laparoscopic cholecystectomy in the treatment of acute cholecystitis: comparison
      of results between early and late cholecystectomy.
AB  - INTRODUCTION: Laparoscopic cholecystectomy has become the gold standard in the
      treatment of symptomatic gallstones. The common opinion about treatment of acute
      cholecystitis is initially conservative treatment due to preventing complications
      of inflamation and following laparoscopic cholecystectomy after 6- 8 weeks.
      However with the increase of laparoscopic experience in recent years, early
      laparoscopic cholecystectomy has become more common. METHODS: We aimed to compare
      the outcomes of the patients to whom we applied early or late cholecystectomy
      after hospitalization from the emergency department with the diagnosis of AC
      between March 2012-2015. RESULTS: We retrospectively reviewed the files of
      totally 66 patients in whom we performed early cholecystectomy (within the first
      24 hours) (n: 33) and to whom we firstly administered conservative therapy and
      performed late cholecystectomy (after 6 to 8 weeks) (n: 33) after hospitalization
      from the emergency department with the diagnosis of acute cholecystitis. The
      groups were made up of patients who had similar clinical and demographic
      characteristics. While there were no statistically significant differences
      between the durations of operation, the durations of hospitalization were longer
      in those who underwent early cholecystectomy. Moreover, more complications were
      seen in the patients who underwent early cholecystectomy although the difference
      was not statistically significant. CONCLUSION: Early cholecystectomy is known to
      significantly reduce the costs in patients with acute cholecystitis. However,
      switching to open surgery as well as increase of complications in patients who
      admitted with severe inflammation attack and who have high comorbidity, caution
      should be exercised when selecting patients for early operation.

PMID- 28451028
TI  - Profile of C-reactive protein, white cells and neutrophil populations in febrile
      children from rural north-eastern Tanzania.
AB  - INTRODUCTION: C-reactive protein (CRP), white blood cell (WBC) and absolute
      neutrophil counts (ANC) are important inflammatory biomarkers in the early
      diagnosis of infections. However, little is known on their profile and usefulness
      in fever case management in children attending outpatient clinic in rural north
      eastern Tanzania. METHODS: Patients aged between 2 and 59 months presenting with
      fever at Korogwe District Hospital were enrolled. Venous blood was collected for
      evaluation of serum CRP, WBC and ANC. Individual patient diagnosis was based on
      integrated management of childhood illness (IMCI) guidelines and laboratory
      investigations (blood and urine cultures). RESULTS: A total of 867 patients were
      enrolled, out of which 691 (79.7%) had complete clinical and laboratory data
      available for analysis. Acute upper respiratory tract infection 284 (41.1%),
      acute gastroenteritis 127 (18.4%) and pneumonia 100 (14.5%) were the most
      frequent diagnoses. The geometric mean levels of serum CRP, WBC and ANC were 10.4
      (95% CI: 9.2 - 11.8), 11.5 (95% CI: 11.1 - 11.9) and 5.5 (95% CI: 5.2 - 5.8),
      respectively. CRP<=20, WBC<=15 (103cells/uL) and ANC<=10 103cells/uL) were
      observed in the majority of the patients with upper respiratory tract infection,
      pneumonia, acute gastroenteritis and non-specific febrile illness. Only serum CRP
      levels were positively correlated with positive blood cultures at a calculated
      cut-off value of 37.3 mg/L, giving a specificity of 77.8% and sensitivity of
      74.2%. CONCLUSION: CRP assessment together with IMCI guidelines may be useful in
      assisting the diagnosis and management of paediatric febrile infections in
      Tanzania.

PMID- 28451029
TI  - Thyroid, cortisol and growth hormone levels in adult Nigerians with metabolic
      syndrome.
AB  - INTRODUCTION: The similarities in presentation of cortisol excess, growth hormone
      deficiency, hypothyroidism and metabolic syndrome suggest that subtle
      abnormalities of these endocrine hormones may play a causal role in the
      development of metabolic syndrome. The aim of this study is to determine the
      levels of cortisol, thyroid and growth hormones in adult Nigerians with metabolic
      syndrome and determine the relationship between levels of these hormones and
      components of the syndrome. METHODS: This was a case control study conducted at
      the Lagos University Teaching Hospital, Lagos, Nigeria. Participants were fifty
      adult men and women with the metabolic syndrome, and fifty, age and sex matched
      males and females without the metabolic syndrome. Metabolic syndrome was defined
      based on the NCEP-ATPIII criteria. Written Informed consent was obtained from the
      participants. Socio demographic and clinical data were collected using a
      structured questionnaire. Venous blood was collected after an over-night fast.
      The Ethics committee of the Lagos University Teaching Hospital, Lagos, Nigeria,
      approved the study protocol. Comparison of continuous variables was done using
      the Student's t test. Correlation analysis was employed to determine the
      associations between variables. Statistical significance was set at P<0.05.
      RESULTS: Triiodotyronine (T3) was significantly decreased (p<0.001) and thyroxine
      (T4 ) significantly increased ( p<0.001) in metabolic syndrome compared to
      healthy controls. T3 correlated positively and significantly with waist
      circumference (p=0.004), glucose (p= 0.002), total cholesterol ( p=0.001) and LDL
      cholesterol ( p<0.001 ) and negatively with body mass index ( p<0.001 )and
      triglyceride ( p=0.026). T4 had a negative significant correlation with waist
      circumference (p=0.004). Cortisol and growth hormone levels were similar in
      metabolic syndrome and controls. Cortisol however had a positive significant
      correlation with waist/hip ratio (p<0.001) while growth hormone correlated
      positively with HDL ( p=0.023)and negatively with diastolic blood pressure
      (p=0.049). CONCLUSION: Thyroid hormones T3 and T4 were associated with metabolic
      syndrome. The thyroid hormones, cortisol and growth hormones correlated with
      components of the syndrome. A therapeutic role may exit for these hormones in the
      management of metabolic syndrome and related disorders.

PMID- 28451030
TI  - Cannabis arteritis.
AB  - Cannabis is the most consumed psychoactive substance by young people. Chronic use
      of cannabis can lead to cannabis arteritis, which is a very rare peripheral
      vascular disease similar to Buerger's disease. It is affecting young adults,
      especially men, consuming cannabis. A 27-year old woman, with no particular past
      medical history except for long-term use of cannabis and tobacco developed a
      digital necrosis in the left hand. She denied using other illicit drugs. Doppler
      ultrasound examination of the upper limbs was unremarkable. Toxicological
      analysis revealed the presence of cannabis in both biological fluid and hair
      strand. Despite medical treatment, cessation of the cannabis and tobacco
      consumption and hyperbaric oxygen therapy, an amputation of necrotic parts was
      then required. This case shows the prolonged use of cannabis could be a risk
      factor for young adult arteritis. Faced with a rapidly progressive arteritis
      occurring in young adult, the physician should consider the history of use of
      cannabis. Hair analysis can be useful for confirmation of the chronic consumption
      of drugs.

PMID- 28451031
TI  - Barriers to postpartum screening for type 2 diabetes: a qualitative study of
      women with previous gestational diabetes.
AB  - INTRODUCTION: Risk of developing type 2 diabetes is increased in women with
      previous gestational diabetes mellitus (GDM). Postpartum glycemic screening is
      recommended in women with recent GDM. But this screening rate is low and the
      reasons are unclear. The aim of this study was to explore the experiences of
      Iranian women with recent GDM on barriers of postpartum screening for diabetes.
      METHODS: This qualitative study was conducted in Tehran, Iran in 2016. Semi
      structured interview was used for data collection. 22 women with recent GDM were
      interviewed. These women gave birth in Tehran hospitals at a minimum of 6 months
      before interview. The missed screening defined as not attending to laboratory for
      Fasting Blood Sugar and/or Oral Glucose Tolerance Test, 6 week to 6 month after
      their child birthing. The data was analyzed by content analysis method. RESULTS:
      Themes and sub-themes that illustrated the barriers to postpartum diabetes
      screening were: inadequate education (about developing diabetes in the future,
      implementation of the screening, and glucometer validity in diagnosis of
      diabetes), perceiving the screening as difficult (feeling comfortable with the
      glucometer, poor laboratory conditions, issues related to the baby/babies, and
      financial problems), improper attitudes toward the screening (unwilling to get
      diagnosed, not giving priority to oneself, having false beliefs) and
      procrastination (gap to intention and action, self-deception and self-regulation
      failure). CONCLUSION: Women with recent GDM reported several barriers for
      postpartum diabetes screening. This study help to develop the evidence-based
      interventions for improving this screening rate.

PMID- 28451032
TI  - Our experience in two cases of type IV laryngotracheoesophageal cleft (LTEC) with
      a diagnosis of antenatal esophageal atresia.
AB  - Laryngotracheoesophageal clefts (LTECs) are rare congenital defects that are
      often accompanied by additional anomalies. The major issues in the treatment of
      these patients are intraoperative exposure insufficiency, technical difficulty of
      the operation, and anesthesia problems originating from the respiratory tract.
      Problems originating from mechanical ventilation and respiratory tract, eating
      disorders and relapse of fistula are among the problems encountered following
      surgery. Most of the time, concomitant additional anomalies also worsen the
      clinical picture. It was our aim with these case reports to report our experience
      in two cases with Type IV LTEC ranging from the inoperable type IV LTEC due to
      additional anomalies mounted up to severe respiratory distress to the carina that
      we operated on with a single stage anterior cervicothoracic approach on its fifth
      day on life.

PMID- 28451033
TI  - [Epidural analgesia in 20 parturients at the Sylvanus Olympio University Hospital
      Center in Lome (Togo)].
AB  - We conducted a prospective and descriptive study on epidural analgesia (EA) at
      the Sylvanus Olympio University Hospital Center in Lome from February to June
      2014. After taking consent from pregnant women selected by simple random sampling
      and in the absence of contraindication for anesthesia (pre-anesthetic assessment
      performed in their 8th month of pregnancy), women were enrolled. Out of 29
      selected women, 20 (69%) underwent EA. The average age was 30.6 +/- 6.6 years:
      primiparas 35%, multiparas 50%, Obese women (BMI> 30)25%. Average number of
      punctures: 1.2 +/- 0.5; blood reflux into the catheter: 5%; dural puncture: 0.
      Delay for anesthesia induction: 8.5 +/- 2, 2mn. Mean dosage of 0.125% isobaric
      bupivacaine: 28.8 +/- 8ml; digital scale at T10min <3 for all parturient women.
      Motor block: 0. Hypotension: 1 case (5%). Mode of delivery: vaginal births 19
      (95%), cesarean section 1 (5%). Respiratory distress in the newborn: 0. Level of
      satisfaction: 9,8 +/- 0.5 / 10. Sylvanus Olympio University Hospital Center in
      Lome provides obstetric EA. While awaiting its availability to all parturient
      women based on human and material resources, the use of epidural analgesia in the
      presence of medical indications would be a first step.

PMID- 28451034
TI  - Free-living amoebae isolated in the Central African Republic: epidemiological and
      molecular aspects.
AB  - Among the many species of free-living amoebae infecting humans, only Naegleria
      fowleri, a few species of Acanthamoeba, Balamuthia mandrillaris recently Sappinia
      diploidea and Paravahlkampfia Francina are responsible for human diseases
      especially deadly encephalitis outside of Acanthamoeba keratitis related. In the
      Central African Republic (CAR), no studies have previously been conducted about
      free amoebae and no suspicious cases of encephalitis or amoebic keratitis was
      reported even though the ecosystem supported the proliferation of these
      microorganisms. The objective of this study was to identify free-living amoebae
      present in CAR and to define the molecular characteristic. Bathing sites and
      cerebrospinal fluid from patients died of bacterial meningitis untagged were
      explored by culture and PCR and the amplicons were sequenced which allowed to
      characterize the species found. Only species of the genus Tetramitus, namely T.
      Entericus, T. waccamawensis and T.sp similar to those already described in the
      world and not pathogenic for humans were found in bathing sites, the
      cerebrospinal fluid meanwhile remained negative. Although no pathogen species
      such as Naegleria fowleri or species of Acanthamoeba have been isolated, this
      study worth pursuing because this investigation was very limited in space because
      of the insecurity in the country.

PMID- 28451035
TI  - [Brain metastasis from rectal adenocarcinoma: about a case and review of the
      literature].
AB  - The most common primary sites for bone metastases in men are lung, prostate,
      kidney, thyroid or bladder. Colorectal origin is rare. Few studies have described
      this type of metastases; the axial skeleton or the pelvis are the most common
      metastasis locations. Craniofacial location is exceptional. We here report the
      case of a 38 years old man treated for metastatic rectal cancer metastasized to
      temporal bone. He initially had undergone surgical procedure for low anterior
      resection, tumor was classified as pT3N0M0; 24 months after the patient had left
      exophthalmos revealing a temporal tumoral process. Evolution and context favoured
      metastasis. In conclusion, this study reporting an exceptional case of
      craniofacial bone metastasis from multi-metastatic colorectal cancer will enrich
      the scarce data reported in the literature related to bone metastases from
      primary colorectal cancer.

PMID- 28451036
TI  - Influence of shift work on the physical work capacity of Tunisian nurses: a cross
      sectional study in two university hospitals.
AB  - INTRODUCTION: This study has been performed to determine the influence of
      rotating shift work on physical working capacity of Tunisian nurses and to design
      recommendations to managers so that they implement effective preventive measures.
      METHODS: It is a cross-sectional design using a standardized questionnaire and
      many physical capacity tests on a representative sample of 1181 nurses and
      nursing assistants from two university hospital centers of the school of Medicine
      of Monastir located in the Tunisian Sahel. 293 participants have been recruited
      by stratified random sampling according to gender and departments. Maximum Grip
      strength, 30s sit-to-stand test, one leg test, Fingertip-to-Floor test, Saltsa
      test and peak expiratory flow were used to assess physical capacity. Work ability
      was assessed through the workability index. RESULTS: Mental and physical loads
      were heavily perceived in shift healthcare workers (p=0.01; p=0.02). The maximum
      grip force was stronger in rotating shift work nurses (p=0.0001). Regarding to
      the seniority subgroups in each kind of work schedule, the Body Mass Index was
      increasing with seniority in both schedules. All the physical tests, were better
      in less-than-ten-year groups. Peak Flow and grip strength were significantly
      better in less-than-ten-year seniority in shift work group. CONCLUSION: There is
      a need to improve the design of the existing shift systems and to reduce as much
      as possible shift schedule as well as to avoid shift schedule for over-10-year
      seniority nurses.

PMID- 28451038
TI  - [Myxoma involving posterolateral leaflet: about a case].
AB  - Cardiac myxomas are the most common type of primary cardiac tumors. They mainly
      affect the interatrial septum and exceptionally the heart valves. Surgical
      excision remains the only therapeutic alternative. We here report the case of a
      69-year old patient with no significant pathological history suffering from NYHA
      class II-III dyspnea associated with lipothymia. Transthoracic echocardiography
      showed a tight calcified aortic narrowing with aortic valve gradient of 58 mmHg.
      A sessile mass of 15mm diameter inserted into the posterolateral leaflet, without
      stenosis or mitral regurgitation evoking an atypical localization of myxomaor or
      fibroelastoma was detected at the level of the mitral valve. The examination was
      supplemented by ETO which confirmed the diagnosis of a mass involving the
      posterolateral leaflet. The patient underwent surgery via median sternotomy,
      under conventional extracorporeal circulation. Left atriotomy allowed to
      objectify a sessile mass of 15mm of diameter involving the auricular wall of the
      friable and easily cleavable posterolateral leaflet. Cauterization of the implant
      base via electric scalpel was then performed without any additional gesture on
      the posterolateral leaflet. Anatomopathologic analysis of the surgical specimen
      confirmed the diagnosis of myxoma. The patient also underwent aortic valve
      replacement with mechanical prosthesis. The postoperative course was uneventful.
      The patient was discharged on postoperative day 8. Cardiac myxoma involving the
      mitral leaflet is very rare. Surgical procedure attempting to resect the widest
      possible surgical margins remains the only therapeutic option to avoid the risk
      of recurrence.

PMID- 28451037
TI  - Colonisation of antibiotic resistant bacteria in a cohort of HIV infected
      children in Ghana.
AB  - Antibiotic use not only selects for resistance in pathogenic bacteria, but also
      in commensal flora of exposed individuals. Little is known epidemiologically
      about antibiotic resistance in relation to people with HIV infection in sub
      Saharan Africa. This study investigated the carriage of antibiotic resistant
      bacteria among HIV infected children at a tertiary hospital in Ghana. One hundred
      and eighteen HIV positive children were recruited at the Korle-Bu Teaching
      Hospital in Ghana and nasopharyngeal specimens were collected from them. The
      specimens were cultured for bacteria, and the isolates were identified by
      standard microbiological methods. Antibiotic susceptibility tests were carried
      out on selected bacterial organisms by the Kirby Bauer method. Bacteria isolated
      from the study subjects included Moraxella catarrhalis (39.8%), coagulase
      negative staphylococci (33.1%), Streptococcus pneumoniae (30.5%), diptheroids
      (29.7%), viridian streptococci (27.1%), Staphylococcus aureus (22.0%),
      Citrobacter spp. (4.2%) and Neisseria meningitidis (0.9%). Prevalence of
      antibiotic resistance of S. pneumoniae ranged from 5.6% (ceftriaxone) to 58.3%
      (cotrimoxazole), M. catarrhalis ranged from 2.1% (gentamicin) to 80.6%
      (ampicillin), and S. aureus ranged from 7.7% (cefoxitin) to 100% (penicillin).
      The prevalence of multiple drug resistance was 16.7% for S. pneumoniae, 57.4% for
      M. catarrhalis and 84.6% for S. aureus. HIV infected children in the study area
      commonly carry multi-drug resistant isolates of several pathogenic bacteria such
      as S. aureus and S. pneumoniae. Infections arising in these patients that are
      caused by S. aureus and S. pneumoniae could be treated with ceftriaxone and
      cefoxitin respectively.

PMID- 28451039
TI  - Frequency of fetal macrosomia and the associated risk factors in pregnancies
      without gestational diabetes mellitus.
AB  - INTRODUCTION: There has been an increased incidence of macrosomic newborns in the
      world and most of the macrosomic newborns are born from non-GDM pregnant women.
      The objective of this study was to determine the frequency and the associated
      risk factors of fetal macrosomia in non-GDM pregnant women. METHODS: A total 4246
      consequtive pregnant women who had no GDM was included the study population. Data
      was collected from hospital database of Balikesir State Hospital between January
      2014 and January 2015. Statistical analysis was carried out using the independent
      samples t-test and chi-squared test. Logistic regression analysis was used to
      determine the relationships between associated risk factors and the presence of
      fetal macrosomia. In this analysis, fetal macrosomia was taken as the dependent
      variable and associated risk factors were taken as independent variables. Results
      are shown as odds ratios (ORs) (95% CI) in the logistic regression analysis.
      RESULTS: 366 of the 4246 pregnant women were diagnosed with fetal macrosomia
      (8.6%). Compared the control women, a statistically significant correlation
      between fetal macrosomia and pre-pregnancy body mass index (BMI), gestational
      weight gain (GWG), parity, advanced maternal age, and male fetal sex was found.
      Maternal BMI, and GWG were the two risk factors most strongly associated with
      macrosomia. CONCLUSION: The prevalance of fetal macrosomia is rising among
      Turkish women. High pre-pregnancy BMI and GWG represent main modifiable risk
      factors for macrosomia and need more attention from health care providers.

PMID- 28451040
TI  - [Burkitt's lymphoma of the oral cavity: about a case].
AB  - Burkitt's lymphoma (LB) is a type of malignant non-Hodgkin's lymphoma originating
      from malignant B-cell transformation and proliferation. Positive confirmation is
      based on biopsy of the tumor mass or bone marrow aspiration revealing the
      presence of tumor cells. We here report the case of a young man, about twenty
      years old, addressed for post tooth extraction gingival swellings evolving for 1
      month. Anatomopathologic examination after biopsy complemented by
      immunohistochemistry confirmed the diagnosis of Burkitt's lymphoma. Treatment was
      based on chemotherapy. Although Burkitt's lymphoma is rare, it is an aggressive
      tumor that represents a real public health problem, hence the role of the
      dentists in early diagnosis, in order to allow rapid and appropriate management
      of the disease which is vital to the healing process.

PMID- 28451041
TI  - Indications and appropriateness of caesarean sections performed in a tertiary
      referral centre in Uganda: a retrospective descriptive study.
AB  - INTRODUCTION: The WHO has identified an ideal caesarean section rate for a nation
      of 10-15%, but much higher rates are seen in tertiary referral centres in
      resource-poor countries. Interventions by the author to improve care and reduced
      unnecessary caesareans were undertaken including staff education and production
      of clinical guidelines. This study aimed to identify indications for caesareans
      and whether the decision to perform caesareans was appropriate in order to
      improve care, and whether the above interventions had an impact on this process.
      METHODS: Two groups of 100 consecutive cases from October 2014 and 100 from
      February 2015 were retrospectively selected that resulted in caesarean. These
      case notes were analysed for demographic data, caesarean indication and
      appropriateness. RESULTS: In 46% of cases the decision for caesarean was
      considered appropriate. No significant difference (p>0.05) was found between the
      two groups in terms of patient demographics or appropriateness of caesarean (43%
      in Oct-14 compared to 48% in Feb-15). The most common group of indications for
      caesarean was dystocia (43.5%) with 28% appropriate; followed by fetal distress
      (18.5%) with 30% appropriate; previous scar (17%) with 85% appropriate;
      malpresentation (10.5%) with 48% appropriate; and maternal compromise (10%) with
      80% appropriate. CONCLUSION: The high number of unnecessary caesareans appeared
      to be related to lack of knowledge and inexperience of staff. Despite attempts to
      address this through teaching the scope of the problem is so large it needs a
      fundamental change in the healthcare system in terms of resources, education,
      continuing professional development and clinical governance.

PMID- 28451042
TI  - [Paget's disease of the nipple].

PMID- 28451043
TI  - Risk factors associated with local complications of erysipelas: a retrospective
      study of 152 cases.
AB  - Erysipelas is a common skin infection. Hemorrhagic, bullous, abcessing and
      necrotic lesions are the major local complications. However, their occurrence
      factors are not clearly known. The aim of this study is to identify the risk
      factors associated with the occurrence of local complications of Erysipelas.
      Medical records from all patients hospitalized with local complications of
      erysipelas admitted to the Military Hospital of Rabat between 2005 and 2015, were
      retrospectively studied. Using an univariate and multivariate statistical study,
      the main characteristics were compared with those from patients with erysipelas
      without local complications. In total, 152 patients were analysed, of whom 72 had
      local disease complications. Using univariate analysis, the factors significantly
      associated with disease complications were found to be: age <= 50 years, female
      gender, heart disease, smoking, taking antibiotics or non-steroid anti
      inflammatory drug before hospitalization, and accelerated sedimentation rate.
      However, in multivariate analysis, taking antibiotics before hospitalization (OR
      5.15, 95% CI 1.28 to 20.72, P = 0.01) and accelerated sedimentation rate (OR 5,
      15, 95% CI 1.00 to 1.06, P = 0.001) were the only independent factors associated
      with complicated erysipelas. Our study showed that prior antibiotics taking and
      higher sedimentation rate are independent risk factors for local complications of
      erysipelas. Patients with these characteristics should be carefully evaluated and
      monitored.

PMID- 28451044
TI  - Fistulized multidrug-resistant tuberculosis.

PMID- 28451045
TI  - [Prelabour rupture of membranes (PROM) at term: prognostic factors and neonatal
      consequences].
AB  - Prelabour rupture of membranes (PROM) at term occurs in 5 to 10% of pregnancies.
      It accounts for a significant proportion of neonatal morbidity and mortality. The
      aim of this case study was to determine the maternal and obstetric prognostic
      factors as well as full-term newborns outcomes in pregnancies complicated by
      prelabour rupture of membranes in patients hospitalized or managed at the
      outpatient clinic. We conducted a retrospective study of all cases of full-term
      infants born to mothers whose pregnancy was complicated by PROM, recorded in the
      neonatology department at the Children's Hospital of Rabat between 1 January and
      31 July 2014. During the study period we collected 144 cases of PROM isolated
      from a total of 2,400 live births (LB), ie a prevalence of live births (6%),
      distributed as follows: 6 cases of PROM (4%) between 6 and 12 hours, 14 cases
      (9.7%) between 12 and 18 hours, 28 cases (19.4%) between 18 and 24 hours and 96
      cases (66.6%) of more than 24 hours. The majority of parturients were within the
      age-group 25-35 years with a rate of 52%. The diagnosis of associated
      chorioamniotitis was retained in 8.3% of cases. Parturients were treated with
      oral or parenteral antibiotic prophylaxis in 28% of cases with clear amniotic
      fluid in 81% of cases. The diagnosis of probable MFI was retained in 46 cases,
      65.2% in the subgroup > 18 h versus 26% and 8.7% in subgroups 12-18 h and <12 h
      respectively. On admission, there was a male predominance of 58.3%, newborns were
      asymptomatic in 76% of cases, they suffered from respiratory distress in 42.8% of
      cases, jaundice in 31.45% of cases, fever in 14.2% of cases and signs of
      neurological distress in 11.5% of cases. All hospitalized newborns (72% of
      cases), were treated with antibiotics for a period ranging from 5 to 10 days with
      an average hospital stay of 2.44 days. This case study highlights the significant
      risk of MFI associated with PROM even in pregnant woman at term. This risk is
      major when rupture of membranes occurs after 24 hours of time. In the majority of
      cases the amniotic fluid is clear and newborns are asymptomatic on admission,
      leaving antibiotic therapy in these newborns a controversial subject.

PMID- 28451047
TI  - [Detection of an unusual case of acute mega cholecystitis associated with cystic
      dilatation of the common bile duct (CBD)].

PMID- 28451046
TI  - [Uncommon mammary-type myofibroblastoma unlike any other: about a case].
AB  - Mammary-type myofibroblastoma (MTMF) is a rare benign mesenchymal tumor,
      initially detected in the breast. Its diagnosis is based on a spectrum of
      clinical, radiological and possibly histological parameters. We here report the
      rare case of a 50 year old male patient with mammary-type myofibroblastoma
      located in the axillary region. The peculiarity of our case lies in the presence
      of numerous mitoses and this was rarely described in the literature. The aim of
      our case study was to raise the problem of differential diagnosis of this rare
      tumor.

PMID- 28451048
TI  - Sexual and reproductive health knowledge and behavior among adolescents living
      with HIV in Zambia: a case study.
AB  - INTRODUCTION: As HIV infected adolescents mature into adulthood, they are
      confronted with issues related to sexuality and sexual reproductive health (SRH).
      An estimated 68,000 adolescents aged 10-19 years are living with HIV in Zambia.
      The current study explores their sexuality and SRH experience and needs. METHODS:
      This was a mixed method analytical cross-sectional study. Adolescents at a
      tertiary hospital were surveyed on their sexuality and SRH experiences. Bivariate
      analyses on SPSS were used to assess factors associated with selected behaviors.
      Emerging themes from open-ended questions qualitative data were explored using
      content analysis. RESULTS: A total of 148 adolescents (63.5% females) aged 15-19
      years were surveyed. Majority (77.0%) had secondary education; 77.2% currently in
      school; 40.1 % had a boy or girlfriend; 15.1% have ever had sex, of whom only
      61.1 % reported consistent condom use. About 68.9 % expressed intention to have
      children; 2.1% of girls had been pregnant before. Of 52 respondents, 19.2% had a
      sexually transmitted infection (STI) before. Not being in school was a
      significant predictor, for knowing where to access information about sex (OR=
      2.53; 95% CI:1.10-5.82; p=0.02), and also for ever gone there (OR=2.61; 95%
      CI:1.04-6.58; p=0.03). CONCLUSION: The survey of HIV infected adolescents
      attending a tertiary hospital in Zambia found that their sexuality and SRH needs
      remain similar to those of the general adolescent population in terms of
      counseling in sexual matters, family planning and STI services. More efforts are
      needed to provide for adolescent health care needs, especially those living with
      HIV.

PMID- 28451049
TI  - Sero-prevalence for Hepatitis B virus among pregnant women attending antenatal
      clinic in Juba Teaching Hospital, Republic of South Sudan.
AB  - INTRODUCTION: Hepatitis B virus infection is a major public health problem
      worldwide and in Africa. This would be the first ever documented study on
      epidemiology of Hepatitis B infections in the newly formed Republic of South
      Sudan. This study was designed to estimate the sero-prevalence of Hepatitis B
      virus infection amongst pregnant women attending antenatal services in Juba.
      METHODS: A cross-sectional study was conducted among pregnant women attending
      antenatal clinic services in Juba Teaching Hospital, in the period between
      December 2012 and March 2013. Any pregnant woman, attending antenatal care
      services at Juba Teaching Hospital, was included if she was a resident of Juba
      County for at least 1 year before pregnancy. A Hepatitis B case was defined as
      any women participating in the study and was found to be positive for HbsAg and
      confirmed by ELISA. RESULTS: This study documented that the prevalence of
      Hepatitis B surface antigen (HBsAg) among pregnant women attending ANC in Juba
      was 11% (31 out of the 280 samples). Other samples tested were indeterminate
      (36%), naturally immune (27.1%), susceptible (23%) and the remaining 1.8% was
      immune due to vaccination. Significant risk factors for Hepatitis B infection
      were loss of partner (OR 4.4 and CI of 1.4-13.9) and history of Jaundice (OR 1.7
      and CI of 1.2-2.1). CONCLUSION: These study findings show that only 29% of
      infants in Juba county are born to immune mothers (naturally or vaccine induced).
      The remaining 70% of babies would be at risk of infection, if a birth dose of
      Hepatitis B is not provided. We therefore recommended introduction of Hepatitis B
      Vaccine birth dose into routine infants' vaccination series to eliminate this
      risk.

PMID- 28451050
TI  - [Tubulopapillary carcinoma in a 17-year-old female patient: a case report and
      review of the literature].
AB  - Tubulopapillary carcinomas account for 10% of renal cell carcinomas. They are
      more frequent in men than in women (sex ratio:8/1). The average period is the
      sixth decade. There are two anatomopathological types:the 1 corresponding to a
      proliferation of basophilic cells and type 2 corresponding to a proliferation of
      eosinophilic cells. We report the case of a 17-year old female patient with no
      particular past medical history presenting to the emergency department with pain
      in the right lumbar fossa and in the right flank associated with hematuria
      evolving for two days before admission, with loss of body weight and
      deterioration of the general status. Clinical examination on admission showed
      poor general condition. The patient was apyretic with blood pressure of 110
      mmhg/70mmhg and a heart rate at 110 beats per minute. Abdominal examination based
      on patient's inspection showed curvature of the right flank with tenderness, and
      guarding on palpation. Hemoglobin levels in the blood were 6 g/dl requiring
      transfusion. Abdominal scan showed voluminous right renal inferior polar tissue
      formation measuring 10 cm/7.8 cm with peri-renal effusion of 17 mm thickness. Two
      days after admission patient's evolution was marked by deglobulisation associated
      with accentuation of the abdominal pains. The patient underwent hemostatic
      nephrectomy. Total enlarged right nephrectomy was performed via subcostal
      incisions. Histological examination revealed type 2 tubulopapillary carcinoma.
      Chest CT scan did not show secondary tumors.

PMID- 28451051
TI  - [Gastric trichobezoar: about a case].
AB  - Trichobezoar is rare, most often asymptomatic condition which can be easily
      diagnosed using oesogastroduodenal fibroscopy. Treatment is usually based on
      surgery. We here report the case of a 16-year old girl who underwent gastric
      trichobezoar extraction via gastrotomy, without complications. The patient even
      underwent psychiatric treatment.

PMID- 28451052
TI  - [Spontaneous renal hematoma].

PMID- 28451054
TI  - Molecular fingerprinting of complex grass allergoids: size assessments reveal new
      insights in epitope repertoires and functional capacities.
AB  - BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is a well-documented
      treatment for allergic disease which involves injections of native allergen or
      modified (allergoid) extracts. The use of allergoid vaccines is a growing sector
      of the allergy immunotherapy market, associated with shorter-course therapy. The
      aim of this study was the structural and immunological characterisation of group
      1 (Lol p 1) IgG-binding epitopes within a complex mix grass allergoid formulation
      containing rye grass. METHODS: HP-SEC was used to resolve a mix grass allergoid
      preparation of high molecular weight into several distinct fractions with defined
      molecular weight and elution profiles. Allergen verification of the HP-SEC
      allergoid fractions was confirmed by mass spectrometry analysis. IgE and IgG
      immunoreactivity of the allergoid preparations was explored and Lol p 1 specific
      IgG-binding epitopes mapped by SPOT synthesis technology (PepSpotTM) with
      structural analysis based on a Lol p 1 homology model. RESULTS: Grass specific
      IgE reactivity of the mix grass modified extract (allergoid) was diminished in
      comparison with the mix grass native extract. A difference in IgG profiles was
      observed between an intact mix grass allergoid preparation and HP-SEC allergoid
      fractions, which indicated enhancement of accessible reactive IgG epitopes across
      size distribution profiles of the mix grass allergoid formulation. Detailed
      analysis of the epitope specificity showed retention of six Lol p 1 IgG-binding
      epitopes in the mix grass modified extract. CONCLUSION: The structural and
      immunological changes which take place following the grass allergen modification
      process was further unravelled revealing distinct IgG immunological profiles. All
      epitopes were mapped on the solvent exposed area of Lol p 1 homology model
      accessible for IgG binding. One of the epitopes was identified as an
      'immunodominant' Lol p 1 IgG-binding epitope (62-IFKDGRGCGSCFEIK-76) and
      classified as a novel epitope. The results from this study support the concept
      that modification allows shorter-course therapy options as a result of providing
      an IgG epitope repertoire important for efficacy. Additionally, the work paves
      the way to help further develop methods for standardising allergoid platforms.

PMID- 28451055
TI  - Hierarchal order in the formation of chloroplast division machinery in the red
      alga Cyanidioschyzon merolae.
AB  - Chloroplasts have evolved from a cyanobacterial endosymbiont and multiply by
      dividing. Chloroplast division is performed by constriction of the ring-like
      protein complex (the PD machinery), which forms at the division site. The PD
      machinery is composed of cyanobacteria-descended components such as FtsZ and
      eukaryote-derived proteins such as the dynamin-related protein, DRP5B. In the red
      alga Cyanidioschyzon merolae, FtsZ ring formation on the stromal side precedes
      PDR1 and DRP5B ring formation on the cytosolic side. In this study, we impaired
      FtsZ ring formation in C. merolae by overexpressing FtsZ just before FtsZ ring
      formation. As a result, PDR1 and DRP5B failed to localize at the chloroplast
      division site, suggesting that FtsZ ring formation is required for the PDR1 and
      DRP5B rings. We further found, by expressing a dominant negative form of DRP5B,
      that DRP5B ring formation begins on the nuclear side of the chloroplast division
      site. These findings provide insight into how the PD machinery forms in red
      algae.

PMID- 28451056
TI  - Neutrophil extracellular trap release driven by bacterial motility: Relevance to
      cystic fibrosis lung disease.
AB  - Neutrophil extracellular trap (NET) formation represents a unique effector
      function of neutrophils (PMN). The mechanism of NET release in response to
      bacteria is largely unknown. We studied the process by which Pseudomonas
      aeruginosa, an opportunistic pathogen, interacts with primary PMNs, and found
      that flagellar swimming motility of the bacterium is essential for inducing NET
      extrusion. Cystic fibrosis (CF) lung disease is associated with P. aeruginosa
      infection and PMN-dominated inflammation. Although NETs are abundant in CF
      airways, the main factors triggering NET release in CF remain unclear. Our study
      implicates that motile P. aeruginosa is a strong NET-inducer in CF. In early
      stages of CF lung disease flagellated, motile isolates of P. aeruginosa are
      characteristic and their interactions with PMNs could lead to NET formation. In
      chronic CF, P. aeruginosa down-regulates its flagellum expression to avoid
      recognition by the immune system and forms biofilms. Flagellated bacteria,
      however, are released from biofilms and could interact with PMNs to form NETs.
      Although flagellated forms likely represent only a small fraction of the total P.
      aeruginosa load in chronic CF, NET release induced by them could have a
      significant impact on inflammation and lung function since flagellated forms
      trigger the most robust response of the immune system including PMNs. Overall, we
      speculate that NET formation driven by motile P. aeruginosa could be a novel,
      significant contributor to pathogenesis at both, early and late stages of CF lung
      disease.

PMID- 28451057
TI  - A network perspective on the virus world.
AB  - Viral evolution is characterized by high rates of horizontal gene transfer and
      fast sequence divergence. Furthermore, there are no universal genes shared by all
      viruses. As a result, distant relationships among viruses are better represented
      by a network than by a tree. Here we discuss 3 network representations of the
      virus world with decreasing levels of complexity, from a multilayer network that
      integrates sequence conservation and patterns of gene sharing to a classic genome
      similarity network. As new tools for network analysis are developed, we expect
      that novel insights into virus evolution will result from the study of more
      complex representations of the virus world.

PMID- 28451058
TI  - Specific phospholipid scramblases are involved in exposure of phosphatidylserine,
      an "eat-me" signal for phagocytes, on degenerating axons.
AB  - Axonal degeneration is a key pathological feature of several neurological
      disorders. Emerging evidence has suggested a pathological connection between
      axonal degeneration and autophagy, a lysosomal degradation pathway. We recently
      reported that GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy
      to promote axonal degeneration. GSK3B-MCL1 pathway affects ATP production locally
      in degenerating axons and the exposure of phosphatidylserine (PS), an "eat-me"
      signal for phagocytes, on degenerating axons, resulting in the failed engulfment
      of axonal debris in vivo. Here we showed that the PS exposure is accomplished by
      phospholipid scramblase activity. This finding provides a novel mechanism that
      local ATP production through autophagy promotes PS exposure on degenerating
      axons. In addition, it opens new perspectives for the understanding of axonal
      autophagy to regulate Wallerian degeneration.

PMID- 28451053
TI  - International consensus (ICON) on: clinical consequences of mite
      hypersensitivity, a global problem.
AB  - Since mite allergens are the most relevant inducers of allergic diseases
      worldwide, resulting in significant morbidity and increased burden on health
      services, the International Collaboration in Asthma, Allergy and Immunology
      (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology
      (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the
      European Academy of Allergy and Clinical Immunology (EAACI), and the World
      Allergy Organization (WAO), has proposed to issue an International Consensus
      (ICON) on the clinical consequences of mite hypersensitivity. The objectives of
      this document are to highlight aspects of mite biology that are clinically
      relevant, to update the current knowledge on mite allergens, routes of
      sensitization, the genetics of IgE responses to mites, the epidemiologic aspects
      of mite hypersensitivity, the clinical pictures induced by mites, the diagnosis,
      specific immunotherapeutic approaches, and prevention.

PMID- 28451059
TI  - Eye tracking uncovered great apes' ability to anticipate that other individuals
      will act according to false beliefs.
AB  - Using a novel eye-tracking test, we recently showed that great apes anticipate
      that other individuals will act according to false beliefs. This finding suggests
      that, like humans, great apes understand others' false beliefs, at least in an
      implicit way. One key question raised by our study is why apes have passed our
      tests but not previous ones. In this article, we consider this question by
      detailing the development of our task. We considered 3 major differences in our
      task compared with the previous ones. First, we monitored apes' eye movements,
      and specifically their anticipatory looks, to measure their predictions about how
      agents will behave. Second, we adapted our design from an anticipatory-looking
      false belief test originally developed for human infants. Third, we developed
      novel test scenarios that were specifically designed to capture the attention of
      our ape participants. We then discuss how each difference may help explain
      differences in performance on our task and previous ones, and finally propose
      some directions for future studies.

PMID- 28451060
TI  - Case Report: Autoimmune Polyglandular Syndrome Type 2 Complicated by Acute
      Adrenal Crisis and Pericardial Tamponade in the Setting of Normal Thyroid
      Function.
AB  - We describe herein a 48-year-old Caucasian woman with a history of autoimmune
      polyglandular syndrome type 2 who presented with pericarditis, pericardial
      effusion, and pericardial tamponade preceded by acute adrenal crisis in the
      setting of normal thyroid function. The case highlights the importance of a rare
      yet important complication of autoimmune polyglandular syndrome type 2 that
      mandates early recognition and intervention.

PMID- 28451062
TI  - Effect of Clostridium perfringens enterotoxin on gastric cancer cells SGC7901
      which highly expressed claudin-4 protein.
AB  - AIM: To investigate the effects of Clostridium perfringens enterotoxin (CPE) on
      gastric cancer cells which highly expressed claudin-4 (CL4) protein. METHODS: In
      this study, we detected expression of CL4 protein in different gastric cancer
      cell lines. Then, we investigated the effects of CPE on SGC7901 cells which
      highly expressed CL4 protein and the effects of CPE on subcutaneous tumor in nude
      mice models. RESULTS: CL4 are highly expressed in SGC7901 cells. CPE expressed
      significant cytotoxicity in SGC7901 cells. Suppression of CL4 expression
      significantly decreased CPE-mediated cytotoxicity. CPE also inhibited tumor
      growth in subcutaneous tumor xenograft models. CONCLUSION: CPE showed CL4
      mediated cytotoxicity on gastric cancer cells SGC7901 and inhibited tumor growth
      in nude mice models.

PMID- 28451061
TI  - Abnormal DNA methylation as a cell-free circulating DNA biomarker for colorectal
      cancer detection: A review of literature.
AB  - Colorectal cancer (CRC) is one of the most prevalent malignancies in the world.
      CRC-associated morbidity and mortality is continuously increasing, in part due to
      a lack of early detection. The existing screening tools such as colonoscopy, are
      invasive and yet high cost, affecting the willingness of patients to participate
      in screening programs. In recent years, evidence is accumulating that the
      interaction of aberrant genetic and epigenetic modifications is the cornerstone
      for the CRC development and progression by alternating the function of tumor
      suppressor genes, DNA repair genes and oncogenes of colonic cells. Apart from the
      understanding of the underlying mechanism(s) of carcinogenesis, the
      aforementioned interaction has also allowed identification of clinical
      biomarkers, especially epigenetic, for the early detection and prognosis of
      cancer patients. One of the ways to detect these epigenetic biomarkers is the
      cell-free circulating DNA (circDNA), a blood-based cancer diagnostic test, mainly
      focusing in the molecular alterations found in tumor cells, such as DNA mutations
      and DNA methylation. In this brief review, we epitomize the current knowledge on
      the research in circDNA biomarkers - mainly focusing on DNA methylation - as
      potential blood-based tests for early detection of colorectal cancer and the
      challenges for validation and globally implementation of this emergent
      technology.

PMID- 28451063
TI  - Bayesian adjustment of gastric cancer mortality rate in the presence of
      misclassification.
AB  - AIM: To correct for misclassification error in registering causes of death in
      Iran death registry using Bayesian method. METHODS: National death statistic from
      2006 to 2010 for gastric cancer which reported annually by the Ministry of Health
      and Medical Education included in this study. To correct the rate of gastric
      cancer mortality with reassigning the deaths due to gastric cancer that
      registered as cancer without detail, a Bayesian method was implemented with
      Poisson count regression and beta prior for misclassified parameter, assuming 20%
      misclassification in registering causes of death in Iran. RESULTS: Registered
      mortality due to gastric cancer from 2006 to 2010 was considered in this study.
      According to the Bayesian re-estimate, about 3%-7% of deaths due to gastric
      cancer have registered as cancer without mentioning details. It makes an
      undercount of gastric cancer mortality in Iranian population. The number and age
      standardized rate of gastric cancer death is estimated to be 5805 (10.17 per
      100000 populations), 5862 (10.51 per 100000 populations), 5731 (10.23 per 100000
      populations), 5946 (10.44 per 100000 populations), and 6002 (10.35 per 100000
      populations), respectively for years 2006 to 2010. CONCLUSION: There is an
      undercount in gastric cancer mortality in Iranian registered data that
      researchers and authorities should notice that in sequential estimations and
      policy making.

PMID- 28451064
TI  - Macroscopic appearance of Type IV and giant Type III is a high risk for a poor
      prognosis in pathological stage II/III advanced gastric cancer with postoperative
      adjuvant chemotherapy.
AB  - AIM: To evaluate whether a high risk macroscopic appearance (Type IV and giant
      Type III) is associated with a dismal prognosis after curative surgery, because
      its prognostic relevance remains elusive in pathological stage II/III (pStage
      II/III) gastric cancer. METHODS: One hundred and seventy-two advanced gastric
      cancer (defined as pT2 or beyond) patients with pStage II/III who underwent
      curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic
      relevance of a high-risk macroscopic appearance was examined. RESULTS: Advanced
      gastric cancers with a high-risk macroscopic appearance were retrospectively
      identified by preoperative recorded images. A high-risk macroscopic appearance
      showed a significantly worse relapse free survival (RFS) (35.7%) and overall
      survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001,
      respectively). A high-risk macroscopic appearance was significantly associated
      with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not
      with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors
      included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors
      including macroscopic appearance. A multivariate Cox proportional hazards model
      for univariate prognostic factors identified high-risk macroscopic appearance (P
      = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent
      prognostic indicator. CONCLUSION: A high-risk macroscopic appearance was
      associated with a poor prognosis, and it could be a prognostic factor independent
      of 13th JGCA stage in pStage II/III advanced gastric cancer.

PMID- 28451065
TI  - Incidence of venous thromboembolism and the role of D-dimer as predictive marker
      in patients with advanced gastric cancer receiving chemotherapy: A prospective
      study.
AB  - AIM: To investigated the incidence and risk factors of venous thromboembolism
      (VTE) in patients with advanced gastric cancer (AGC) receiving chemotherapy.
      METHODS: All consecutive chemotherapy-naive patients with AGC who would receive
      palliative chemotherapy between November 2009 and April 2012 in our hospital were
      recruited. Their pretreatment clinical and laboratory variables, including D
      dimer, were recorded. The frequency of VTE development and survival rates during
      each chemotherapy cycle and regularly thereafter were assessed. RESULTS: A total
      of 241 patients enrolled between November 2009 and April 2012 were analyzed.
      During a median follow-up duration of 10.8 mo (95%CI: 9.9-11.7), 27 patients
      developed VTE and the incidence of VTE was 17.5% (95%CI: 10.5-24.0, 12.0
      events/100 person-years). The 6-mo and 1-year cumulative incidences were 7.8%
      (95%CI: 4.2%-11.4%) and 12.4% (95%CI: 7.3-17.2), respectively. Thirteen (48.1%)
      patients were symptomatic and the other 14 (51.9%) patients were asymptomatic. In
      multivariate analysis, pretreatment D-dimer level was the only marginally
      significant risk factor associated with VTE development (hazard ratio = 1.32;
      95%CI: 1.00-1.75, P = 0.051). CONCLUSION: The incidence of VTE is relatively high
      in patients with AGC receiving chemotherapy, and pretreatment D-dimer level might
      be a biomarker for risk stratification of VTE.

PMID- 28451066
TI  - Helicobacter pylori recurrence after eradication in Latin America: Implications
      for gastric cancer prevention.
AB  - AIM: To estimate Helicobacter pylori (H. pylori) recurrence rate in Latin
      America, a region with a significant H. pylori prevalence and gastric cancer
      burden. METHODS: PubMed, LILACS, SciELO, Cochrane databases and abstracts from
      relevant meetings were reviewed. Information collected included: Participants'
      characteristics, recruitment strategy, diagnostic modality, treatment arms,
      follow-up and recurrence rates. Recurrence was calculated using 100-patients-year
      rates, and data were pooled using a random effects model. The I2 statistic
      assessed between study heterogeneity. Meta-regression analyses evaluated for
      effect modifying variables. RESULTS: Literature search yielded 163 articles.
      Twelve studies involving 4848 patients from 9 countries met inclusion criteria.
      Four hundred and thirty-two reinfections were recorded in 5487 person-years of
      follow-up. Pooled analysis showed a recurrence rate of 7.9 cases per 100 person
      years (95%CI: 5.3-10.5). Meta-regression revealed that neither the antibiotic
      schema, a second antibiotic course, nor the diagnostic modality had an impact on
      the observed risk of recurrence. The recurrence rate in the first year after
      treatment, predominantly recrudescence, was 11.2 (6.1-16.4) per 100 patient
      years. Recurrence in subsequent years, was only 6.2 (3.8-8.7). CONCLUSION: H.
      pylori recurrence rates in Latin America are significant, and with geographic
      variability, yet are acceptable based upon the current literature for
      consideration of large scale intervention trials. Further research in Latin
      America is warranted to evaluate the efficacy, cost-effectiveness, and potential
      adverse outcomes of proposed eradication programs.

PMID- 28451067
TI  - Prolonged grief, depression, and posttraumatic stress in disaster-bereaved
      individuals: latent class analysis.
AB  - Background: Hundreds of individuals lost one or more significant others in the
      MH17 plane crash in 2014 in Ukraine. The current study is the first to explore
      subgroups of disaster-bereaved individuals based on presence of psychopathology
      clusters. This may inform the development of diagnostic instruments and tailored
      interventions. Objective: Aims of the current study were to examine (1) subgroups
      based on presence of prolonged grief disorder (PGD), major depressive disorder
      (MDD), and posttraumatic stress disorder (PTSD) symptom clusters and (2)
      associations between class membership, disaster-related variables (i.e.
      experiencing multiple losses, conducting multiple burials for the same deceased,
      and time to confirmation of death), and a sense of unrealness. Method: Self-rated
      PGD (10 items of the Traumatic Grief Inventory represented in two symptom
      clusters), MDD (16-item Quick Inventory Of Depressive Symptomatology represented
      in one symptom cluster), and PTSD (20-item PTSD Checklist for DSM-5 represented
      in four symptom clusters) from 167 participants were subjected to latent class
      analysis to identify subgroups (i.e. classes). Correlates of class membership
      were assessed using the three-step approach. Results: A three-class solution
      yielded the best model fit. Class 1 (Resilient class; 20.0%) was predominantly
      characterized by low probability of PGD, MDD, and PTSD symptom clusters, class 2
      (PGD class; 41.8%) by moderate to high probability of presence of PGD, and class
      3 (Combined class; 38.2%) by moderate to high probability of presence of PGD,
      MDD, and PTSD symptom clusters. Compared with the Resilient class, a sense of
      unrealness was more likely to be experienced by individuals in the PGD class and
      the Combined class. Conclusions: Our results indicate that subgroups of disaster
      bereaved individuals can be distinguished based on the presence of PGD, MDD, and
      PTSD symptom clusters. A sense of unrealness was the strongest distinguishing
      feature of the subgroups.

PMID- 28451069
TI  - Posttraumatic growth and depreciation six years after the 2004 tsunami.
AB  - Background: Posttraumatic growth (PTG) has been reported after various types of
      potentially traumatic events, as a part of the personal recovery process among
      survivors. Even negative changes in survivors' life view, known as posttraumatic
      depreciation (PTD), have been identified as an additional aspect in the personal
      recovery processes. Objective: To examine how the type of exposure experienced by
      survivors of a natural disaster, the 2004 Southeast Asia tsunami, influenced self
      reported PTG and PTD six years later (T2). Additionally, the study examined the
      relations between psychological distress and posttraumatic stress symptoms (PTSS)
      14 months after the disaster (T1), to PTG and PTD, respectively at T2. Finally,
      the study examined whether psychological distress and PTSS (T1) could have a
      mediating effect on PTG and PTD at T2. Method: The participants were 848 tsunami
      survivors living in Stockholm, Sweden who responded to a questionnaire at 14
      months (T1) and six years (T2) after the tsunami. The material was analysed using
      linear regression and pathway analysis. PTG and PTD were measured on separate
      scales. Results: The type of exposure was significant related to both PTG and PTD
      six years later (T2). Those experiencing a combination of various types of
      exposure (including threat to life and bereavement) reported higher scores for
      both PTG and PTD. There were significant positive correlations between PTSS at T1
      and PTG /PTD at T2, and somewhat lower correlations between psychological
      distress at T1 and PTG/PTD at T2. Both PTSS and psychological distress at T1 were
      significant mediating variables for both PTG and PTD at T2. Conclusions: Studying
      survivors' various types of exposure and subsequent changed view of life - both
      PTG and PTD - resulted in a broadened understanding of the complexity of
      reactions and the recovery process among survivors.

PMID- 28451068
TI  - Preventing PTSD with oxytocin: effects of oxytocin administration on fear
      neurocircuitry and PTSD symptom development in recently trauma-exposed
      individuals.
AB  - Background: Posttraumatic stress disorder (PTSD) is a debilitating psychiatric
      disorder which develops in approximately 10% of trauma-exposed individuals.
      Currently, there are few early preventive interventions available for PTSD.
      Intranasal oxytocin administration early posttrauma may prevent PTSD symptom
      development, as oxytocin administration was previously found to beneficially
      impact neurobiological (e.g. amygdala reactivity) and socio-emotional PTSD
      vulnerability factors. Objective: The overall aim of this dissertation was to
      investigate the potential of intranasal oxytocin administration as early
      preventive intervention for PTSD. Methods: We performed a functional magnetic
      resonance imaging (fMRI) study to assess the acute effects of a single
      administration of oxytocin on the functional fear neurocircuitry - consisting of
      the amygdala and (pre)frontal brain regions - in recently trauma-exposed
      emergency department patients (range n = 37-41). In addition, we performed a
      multicentre randomized double-blind placebo-controlled clinical trial (RCT) to
      assess the efficacy of repeated intranasal oxytocin administration early after
      trauma for preventing PTSD symptom development up to six months posttrauma (n =
      107). Results: In our fMRI experiments we observed acutely increased amygdala
      reactivity to fearful faces and attenuated amygdala-ventromedial and
      ventrolateral prefrontal cortex functional connectivity after a single oxytocin
      administration in recently trauma-exposed individuals. However, in our RCT we
      found that repeated intranasal oxytocin administration early posttrauma reduced
      subsequent PTSD symptom development in recently trauma-exposed emergency
      department patients with high acute PTSD symptoms. Conclusions: These findings
      indicate that repeated intranasal oxytocin is a promising early preventive
      intervention for PTSD for individuals at increased risk for PTSD due to high
      acute symptom severity. Administration frequency dependent effects of oxytocin or
      the effects of oxytocin administration on salience processing may serve as
      explanatory frameworks for the contrasting oxytocin effects on anxiety-related
      measures in our clinical and neuroimaging studies.

PMID- 28451070
TI  - Like a bridge over troubled water? A longitudinal study of general social
      support, colleague support, and leader support as recovery factors after a
      traumatic event.
AB  - Background: Whereas the association between social support and psychological
      distress has been well-established through both cross-sectional and longitudinal
      studies, less is known about whether social support influences rate of change in
      psychological distress over time. Nor is it clear whether social support predicts
      baseline psychological distress, or, more importantly, whether social support may
      contribute to more rapid recovery following trauma exposure. Objective: This
      study aimed to determine the extent to which social support contributed to the
      recovery process among individuals with psychological distress after being
      exposed to trauma. Methods: Prospective survey data from ministry employees were
      collected 10, 22, and 34 months after the 2011 Oslo bombing that targeted the
      governmental quarters. We explored recovery in a clinical subsample (N = 238) of
      individuals with elevated levels of psychological distress (defined as mean 10
      item Hopkins symptom checklist score > 1.85) one year after the event. A linear
      latent growth curve of psychological distress with general social support from
      friends and family, colleague support, and leader support as predictors was
      examined. Results: High levels of general social support and leader support were
      independently associated with a more rapid decline in psychological distress over
      time. Conclusions: General social support, as well as support from a leader in
      one's working life, may facilitate recovery from psychological distress after
      exposure to a traumatic event. Enhancing social support from family and friends,
      as well as in work settings, may benefit those with psychological distress
      following a traumatic workplace event.

PMID- 28451071
TI  - Understanding the role of childhood abuse and neglect as a cause and consequence
      of substance abuse: the German CANSAS network.
AB  - Background: Substance use disorders (SUD) belong to the most frequent behavioural
      consequences of childhood abuse and neglect (CAN). If parents are concerned, SUD
      are also an important risk factor for CAN. The relationship between CAN and SUD
      remains poorly understood. There is a need of adequate treatments for SUD
      patients suffering from the consequences of CAN, as well as for approaches to
      prevent CAN by parents with SUD. Objective: To describe the aims and the
      structure of a German research network on relationships between CAN and SUD
      (CANSAS network). Method: Descriptive overview of the aims, and the different
      project clusters of the network. Results: The aims of the CANSAS network are: (1)
      to examine relationships between SUD and CAN; (2) to examine the effects of an
      evidence-based treatment for SUD patients with posttraumatic disorders; and (3)
      to provide SUD services with tools to diagnose CAN, and to assess the risk of
      maltreatment among parents with SUD. The aims of the network are addressed by six
      projects in three different project clusters (mediators and risk factors,
      evidence-based treatment, and improvement of services). Conclusions: It is
      expected that the CANSAS network will advance the understanding of relationships
      between early adversity and substance use disorders. It will bring forward the
      discussion about promising treatments for SUD patients with experiences of CAN.
      Finally it will provide services with measures to identify patients with CAN, and
      with tools to break the trans-generational cycle of adversity.

PMID- 28451072
TI  - Screening for birth-related PTSD: psychometric properties of the Turkish version
      of the Posttraumatic Diagnostic Scale in postpartum women in Turkey.
AB  - Background: Evidence suggests that 4% of women develop posttraumatic stress
      disorder (PTSD) after childbirth, with a potentially negative impact on women and
      families. Detection of postpartum PTSD is essential but few measures have been
      validated in this population. Objective: This study aimed to examine psychometric
      properties of the Turkish version of the Posttraumatic Diagnostic Scale (PDS) to
      screen for birth-related PTSD among postpartum women and identify factorial
      structure of PTSD after birth. Method: PDS was administered to 829 postpartum
      women recruited from three maternity hospitals in Turkey. Participants with PTSD
      (N = 68) and a randomly selected group of women without PTSD (N = 66), underwent
      a structured clinical interview (SCID). Results: PDS demonstrated high internal
      consistency (alpha = .89) and test-retest reliability between 4-6 weeks and 6
      months postpartum (rs = .51). PDS showed high concurrent validity with other
      measures of postpartum psychopathology, rs (829) = .60 for depression and rs
      (829) = .61 for anxiety. Satisfactory diagnostic agreement was observed between
      diagnoses obtained by PDS and SCID, with good sensitivity (92%) and specificity
      (76%). Exploratory and confirmatory factor analyses revealed that the latent
      structure of birth-related PTSD was best identified by a three-factor model: re
      experiencing and avoidance (RA), numbing and dysphoric-arousal (NDA) and
      dysphoric-arousal and anxious-arousal symptoms (DAA). Conclusions: The findings
      supported use of PDS as an effective screening measure for birth-related PTSD
      among postpartum women.

PMID- 28451073
TI  - Response to 'The factor structure of complex posttraumatic stress disorder in
      traumatized refugees'.

PMID- 28451074
TI  - Response to the Letter to the Editor regarding 'The factor structure of complex
      posttraumatic stress disorder in traumatized refugees'.

PMID- 28451075
TI  - Ever at the ready for events that never happen.
AB  - Stress, whether daily stress, work stress or traumatic stress, is unhealthy. This
      lecture covers three recent theoretical approaches in explaining the mechanisms
      underlying the influence of psychological stress on somatic health. It is argued
      that stress research should focus less on stressors themselves and put more
      emphasis on prolonged stress responses. Three mechanisms are identified that
      cause this unhealthy prolonged stress response: first, the partly-proven
      mechanism of perseverative cognition; second, the mechanism of unconscious
      stress, which is currently being explored; and third, the notion of the stress
      response being a default response that is inhibited only when safety is
      perceived. All three mechanisms are deeply rooted in millions of years of our
      evolution. Although the dangers of the past have virtually disappeared, many of
      us remain ever at the ready for events that never happen.

PMID- 28451077
TI  - Continuities in the HIV/AIDS Policy Debate in South Africa.
AB  - Wouters et al. (2010) critiqued the prospects of success for South Africa's new
      National Strategic Plan (NSP) for HIV/AIDS; they stressed the need to mobilize
      people living with HIV/AIDS and their communities in order to implement the
      comprehensive HIV/AIDS strategy. Utilizing the South African sample from the
      Fourth Round of the Afrobarometer survey, this paper identifies the factors which
      predicted respondent selection of HIV/AIDS as an important issue for the
      government to address. The identification of HIV/AIDS as an important
      governmental problem became the study's dependent variable. Other possible
      important factors were whether respondents had personal knowledge of HIV/AIDS,
      meaning they knew someone who died of AIDS, poverty, and their assessments of the
      way the government was handling the HIV/AIDS crisis. Respondent background and
      demographic characteristics were also included in a logistic regression analysis.
      The results identified three factors that predicted respondent choice of
      HIV/AIDS: race, especially being a Black South African, the choice of health as a
      governmental priority, and the rural-urban dimension. The conclusion was that
      HIV/AIDS, as opposed to health, should be the focus of campaigns designed to
      mobilize public support of comprehensive HIV/AIDS strategies in South Africa.

PMID- 28451076
TI  - DSM-5 and ICD-11 as competing models of PTSD in preadolescent children exposed to
      a natural disaster: assessing validity and co-occurring symptomatology.
AB  - Background: Major revisions have been made to the DSM and ICD models of post
      traumatic stress disorder (PTSD). However, it is not known whether these models
      fit children's post-trauma responses, even though children are a vulnerable
      population following disasters. Objective: Using data from Hurricane Ike, we
      examined how well trauma-exposed children's symptoms fit the DSM-IV, DSM-5 and
      ICD-11 models, and whether the models varied by gender. We also evaluated whether
      elevated symptoms of depression and anxiety characterized children meeting PTSD
      criteria based on DSM-5 and ICD-11. Method: Eight-months post-disaster, children
      (N = 327, 7-11 years) affected by Hurricane Ike completed measures of PTSD,
      anxiety and depression. Algorithms approximated a PTSD diagnosis based on DSM-5
      and ICD-11 models. Results: Using confirmatory factor analysis, ICD-11 had the
      best-fitting model, followed by DSM-IV and DSM-5. The ICD-11 model also
      demonstrated strong measurement invariance across gender. Analyses revealed poor
      overlap between DSM-5 and ICD-11, although children meeting either set of
      criteria reported severe PTSD symptoms. Further, children who met PTSD criteria
      for DSM-5, but not for ICD-11, reported significantly higher levels of depression
      and general anxiety than children not meeting DSM-5 criteria. Conclusions:
      Findings support the parsimonious ICD-11 model of PTSD for trauma-exposed
      children, although adequate fit also was obtained for DSM-5. Use of only one
      model of PTSD, be it DSM-5 or ICD-11, will likely miss children with significant
      post-traumatic stress. DSM-5 may identify children with high levels of comorbid
      symptomatology, which may require additional clinical intervention.

PMID- 28451078
TI  - Evaluation of OraQuick(r) HIV-1/2 as Oral Rapid Test.
AB  - As Cameroon scales up its national HIV/AIDS control program, evaluating the
      performance of commercially available tests for accurate and cost effective
      diagnostics becomes essential. A cross-sectional study assessed the performance
      of an HIV oral rapid test. A total of 1520 participants consented to participate
      in the study. After counselling, they were tested for HIV using the national
      algorithm followed by OraQuick. Results of the national algorithm were compared
      to those of OraQuick, for sensitivity, specificity, positive predictive and
      negative predictive values. 62% of participants were male, and 1% was reported
      HIV-positive following the national algorithm. The OraQuick test had 93%
      sensitivity, 99% specificity, 99.93% NPV and 90% PPV (95% CI, Kappa 0.965).
      Though more expensive (2-6x) compared to the national algorithm tests, oral
      mucosal transudate-based test demonstrated good performance. Therefore, it could
      be implemented in resource-constrained settings if subsidized and could increase
      participation since less invasive with no blood accident exposure.

PMID- 28451080
TI  - Assertiveness and Attitudes of HIV/AIDS Orphaned Girls Towards Education in
      Kampala (Uganda).
AB  - Whereas HIV/AIDS prevalence has been declining in Uganda from 30% to less than
      10% in the last 2 decades, the number of HIV/AIDS orphaned girls in secondary
      schools is still high and girl children have tended to carry the heaviest burdens
      of family responsibilities thereby adversely affecting their assertiveness and
      attitudes towards education. Assertiveness is a critical life skill that enables
      a person to state an opinion, claim a right, or establish authority and it is
      important to improve attitude towards education. This study examined the
      relationship between assertiveness and attitude towards education of HIV/AIDS
      orphaned and non-orphaned adolescent school girls in Kampala. The California
      Psychological Inventory (CPI) Dominance (Do) Assertiveness Scale and the Attitude
      Scale were administered to 225 students consecutively selected from 6 secondary
      schools in Kampala. HIV/AIDS Orphaned girls had lower levels of assertiveness and
      most had a negative attitude towards education compared to non-orphaned girls.
      Girls orphaned to HIV/AIDS were less assertive compared to those orphaned by
      other causes. There was a positive relationship between assertiveness and
      attitude towards education among orphaned adolescent secondary school girls in
      Kampala. Girls orphaned to HIV/AIDS were less assertive compared to other school
      girls and have a poor attitude towards education.

PMID- 28451079
TI  - Comparing Influenza Positivity Rates by Real-Time RT-PCR, Elisa and Viral Culture
      Methods in Cote D'Ivoire, West Africa, in 2009.
AB  - Detection of circulating influenza strains is a key public health concern
      especially in limited-resource settings where diagnosis capabilities remain a
      challenge. As part of multi-site surveillance in Cote d'Ivoire during the 2009
      influenza A(H1N1) pandemic, we had the opportunity to test respiratory specimens
      collected from patients with acute respiratory illness (ARI). We analyzed and
      compared the percentage of specimens testing positive using three laboratory
      methods (rtRT-PCR, ELISA, viral culture). From January to October 2009, 1,356
      respiratory specimens were collected from patients with acute respiratory illness
      and shipped at the WHO NIC (Institut Pasteur) Cote d'Ivoire, and 453 (33%) tested
      positive for influenza by one or more laboratory methods. The proportion of
      positive influenza tests did not differ by the sex or age of the patient or
      presenting symptoms, but did differ depending on the timing and site of specimen
      collection. Of the 453 positive specimens, 424 (93.6%) were detected by PCR, 199
      (43.9%) by ELISA and 40 (8.8%) by viral culture. While seasonal influenza A(H1N1)
      virus strains were prominent, only four 2009 pandemic influenza A(H1N1) cases
      were detected. Use of molecular biology method (rtRT-PCR) increased sensitivity
      and diagnosis capabilities. Among all three methods used, rRT-PCR was the most
      sensitive and rapid method. More capacity building is still required for viral
      culture. Need to collect denominator data in order to have an accurate estimate
      of the burden of influenza. There was delayed introduction of pandemic influenza
      A(H1N1)2009 in Cote d'Ivoire.

PMID- 28451082
TI  - The effect of dairy consumption on the prevention of cardiovascular diseases: A
      meta-analysis of prospective studies.
AB  - Introduction: There is no global consensus on the relationship of dairy products
      with cardiovascular diseases. This study was conducted to evaluate the effect of
      the consumption of dairy products on cardiovascular diseases, including stroke
      and coronary heart disease (CHD). Methods: Important electronic databases such as
      the Scopus, Science Direct, and PubMed were evaluated up to September 2014. All
      prospective cohort studies that evaluated the relationship between dairy products
      consumption and cardiovascular diseases were included regardless of their
      publication date and language. The study participants were evaluated regardless
      of age, sex, and ethnicity. The STROBE checklist was used to assess quality of
      the study. Two investigators separately selected the studies and extracted the
      data. The designated effects were risk ratio (RR) and hazard ratio (HR). The
      random effect model was used to combine the results. Results: Meta-analysis was
      performed on 27 studies. There were 8648 cases of cardiovascular diseases (CVD),
      11806 cases of CHD, and 29300 cases of stroke. An inverse association was found
      between total dairy intake and CVD (RR=0.90, 95% CI: 0.81-0.99) and stroke
      (RR=0.88, 95% CI: 0.82-0.95) while no association was observed between total
      dairy intake and CHD. The total diary intake was associated with decreased
      mortality of stroke (RR=0.80, 95% CI: 0.76-0.83) although it had no association
      with its incidence (RR=0.96, 95% CI: 0.88-1.04). Conclusion: This is the first
      meta-analysis of the relationship of total dairy intake with CVD. This study
      showed an inverse relationship between total dairy intake and CVD while no
      relationship was found for CHD. Considering the limited number of studies in this
      regard, more studies are required to investigate the effect of different factors
      on the association of dairy intake and CVD.

PMID- 28451083
TI  - Prevalence of cardio-metabolic risk factors in a nationally representative sample
      of Iranian adolescents: The CASPIAN-III Study.
AB  - Introduction: The aim of the present study is to explore the prevalence and mean
      of cardiometabolic risk factors and liver enzymes of Iranian adolescents living
      in regions with different socioeconomic status (SES). To the best of our
      knowledge this is the first study reporting these data at sub-national level in
      Iran. Methods: This multi-centric study was performed in 2009-2010 on a
      stratified multi-stage probability sample of 5940 students aged 10-18 years,
      living in urban and rural areas of 27 provinces of Iran. Trained healthcare
      professionals measured anthropometric indices, systolic and diastolic blood
      pressures (SBP, DBP) according to standard protocols. Fasting venous blood was
      examined for fasting blood sugar (FBS), lipid profile and liver enzymes including
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We
      classified the country into four sub-national regions based on criteria of the
      combination of geography and SES. Mean and frequency of risk factors were
      compared across these regions. Results: The mean of body mass index had linear
      rise with increase in the regions' SES (P for trend <0.001). The mean levels of
      DBP, total cholesterol (TC), high-density lipoproteincholesterol (HDL-C),
      triglycerides (TG), FBS, ALT, and AST had linear association with regions' SES in
      the whole population and in both genders (P for trend < 0.05), whereas the
      corresponding figure was statistically significant for the mean SBP only in girls
      (P for trend: 0.03) and for the mean of LDL-C in the whole population and in boys
      (P for trend <0.001). In total and in both genders, there was an escalating trend
      in the prevalence of elevated FBS, TC and liver enzymes, low HDL-C, and metabolic
      syndrome by increase in the SES of the region(P for trend <0.01). Conclusion:
      This study proposes that in addition to national health policies on preventing
      cardiometabolic risk factors, specific interventions should be considered
      according to the regional SES level.

PMID- 28451084
TI  - Effects of a therapeutic lifestyle change diet and supplementation with Q10 plus
      L-carnitine on quality of life in patients with myocardial infarction: A
      randomized clinical trial.
AB  - Introduction: Myocardial infarction (MI) has a deleterious effect on quality of
      life (QoL), which can affect cardiac prognosis after MI. Thus, new strategies
      have to be identified for improving the QoL. To our knowledge, no studies have
      been conducted on the impact of therapeutic lifestyle change (TLC) diet and L
      carnitine plus Q10 supplementation on QoL after MI. Methods: The study aimed to
      measure 128 MI patients' QoL using MacNew QoL questionnaire (global scales and
      physical, emotional, and social subscales) before and 3 months after the
      intervention. The patients were divided into 4 groups. Group A received TLC diet,
      group B orally received Q10 150 mg/d and L-carnitine 1200 mg/d, and group C
      received a combination of carnitine plus Q10 and TLC diet. Finally, group D, as
      the control group, only underwent the routine care. Results: The results showed a
      significant increase in MacNew questionnaire's physical, emotional, and social
      subscales in the four groups after the intervention. The results of within-group
      analysis showed that the physical and emotional subscales changed significantly
      (P < 0.001 and P < 0.022, respectively). In the emotional subscale, TLC group
      showed a significant improvement compared to groups B and D (P < 0.019 and P <
      0.001, respectively), but not group C (P < 0.681). In the physical subscale, Q10
      plus L-carnitine group showed a significant improvement compared to groups A and
      D (P < 0.001 and P < 0.0001, respectively), but not group C (P < 0.860). In the
      global scale, combination of carnitine plus Q10 and TLC diet group demonstrated a
      considerable improvement compared to groups A, B, and D (P < 0.001, P < 0.001,
      and P < 0.001, respectively). Nevertheless, the results of within-group analysis
      revealed no significant differences among the four groups regarding the social
      subscale (P < 0.229). Conclusion: Both TLC diet and supplementation with Q10 and
      L- carnitine had a positive effect on the physical and emotional subscales of
      MacNew questionnaire and may improve post-MI prognosis. Based on the results,
      combination of Q10 plus L-carnitine and TLC die can be a potential intervention
      for improving QoL and secondary prevention.

PMID- 28451085
TI  - Two-dimensional strain echocardiography for detection of cardiotoxicity in breast
      cancer patients undergoing chemotherapy.
AB  - Introduction: Two-dimensional (2D) strain echocardiography has emerged as a novel
      method for early diagnosis of myocardial dysfunction in patients receiving
      anthracycline chemotherapy. Certain myocardial segments might be more vulnerable
      for development of dysfunction. Methods: Sixty-three patients with breast cancer
      who were deemed amenable for anthracycline chemotherapy were prospectively
      studied from March 2013 to March 2015 in University Hospital settings. Global
      left ventricular (LV) ejection fraction (EF), fractional shortening and the
      strain over 17 segments of the LV were examined using 2-dimensional transthoracic
      echocardiography (TTE) before and after chemotherapy. More than 15% reduction in
      longitudinal peak systolic strain (LPSS) was considered significant. Results: The
      mean age of patients was 47 +/- 10 years. LVEF was 59.7 +/- 6.5% at baseline.
      Significant reduction of global LPSS was detected in 13% of patients. A
      significant LPSS reduction occurred in 32.4% of 1071 segments examined following
      chemotherapy. LPSS significantly decreased in 28% of apical segments, 31% of mid
      segments and 37% of basal segments. LPSS reduction occurred more frequently over
      the basal segments than all other segments (P = 0.031). Conclusion: Segmental
      pattern appears to exist in LPSS reduction following anthracycline therapy. As
      significant segmental decreases can be seen in the setting of unchanged global
      LPSS, segmental evaluation of LPSS might be a more accurate way for assessment of
      myocardial function.

PMID- 28451086
TI  - Does aortic pulse wave velocity have any prognostic significance in advanced
      heart failure patients?
AB  - Introduction: Noninvasive measurement of arterial stiffness by pulse-wave
      velocity (PWV) has prognostic value in different sub groups of cardiovascular
      disorders. We aimed to measure the PWV in advanced heart failure (HF) patients
      with reduced left ventricular ejection fraction (LVEF) and investigate whether it
      has any prognostic significance in this group of patients. Methods: Between 2013
      to 2015 patients with a diagnosis of advanced HF (LVEF <= 30%) scheduled for
      right heart catheterization (RHC) were included in our study. PWV was measured
      before RHC in each patient using vascular explorer device (Enverdis GmbH) in
      catheterization laboratory. The patients were subsequently followed for 6 months
      and their hospitalization or death (composite of all-cause death/hospitalization)
      were recorded. Results: A total of 50 patients (38 men) were enrolled. The mean
      (SD) of age was 45 (16) years. The mean PWV was 6.8 m/s. There was no
      statistically significant correlation between the PWV and the clinical,
      echocardiographic and RHC data. The PWV was not different in patients with or
      without composite of all-cause death/hospitalization (7.3 versus 6.3, P > 0.05).
      In this study cardiac output (CO) (beta = -0.53, P = 0.02, odds ratio = 0.6, 95%
      CI = 0.4-0.9), pulse pressure (PP) (beta = -0056, P = 0.03, odds ratio=0.95, 95%
      CI = 0.89-0.99) and age (beta = -0.045, P = 0.05, odds ratio = 0.96, 95% CI = 0.9
      1.001) were independent predictors of composite of all-cause death/
      hospitalization. Conclusion: In patients with advanced systolic HF, PWV may not
      be a good prognostic factor and does not have any added value over previous well
      known prognostic factors.

PMID- 28451088
TI  - The association of right coronary artery conus branch size and course with ST
      segment elevation of right precordial leads and clinical outcome of acute
      anterior myocardial infarction.
AB  - Introduction: Coronary artery disease is the leading cause of death worldwide and
      electrocardiogram (ECG) is a reliable diagnostic tool to determine a myocardial
      infarction. The present study tried to compare the relationship between the ECG
      findings and angiographic findings in patients with acute anterior myocardial
      infarction. Methods: Seventy-four patients with acute anterior ST elevation
      myocardial infarction (Ant- STEMI) presenting to the emergency room in the first
      12 hours after the onset of symptoms were studied. Upon admission, a full 14-lead
      ECG (including leads V3R and V4R) were performed. Angiographic and ECG findings,
      as well as clinical outcome were compared between two groups. The statistical
      tests including Chi-square and independent t-test were used for data analysis.
      Results: Small conus branch was seen in 52 (70.3%) and large conus in 22 ( 29.7%)
      patients. STE in right-sided leads and heart failure were significantly higher in
      small conus branch group versus large conus branch (88.6% vs 11.4%, P < 0.001 and
      34.6% vs 9.1%, P = 0.02 respectively). There was no significant difference in
      mortality rate between the two groups (5.8% in small conous group vs 0% in large
      conus group, P = 0.55). There was a significant difference in major adverse
      cardiac events (MACE) between the two groups (51.9% in small conous group vs
      18.2% in large conus group, P = 0.01). Conclusion: In patients with anterior MI,
      small conus branch was associated with higher rate of major adverse cardiac
      events mostly because of increased rate of acute heart failure.

PMID- 28451087
TI  - Physical inactivity and associated factors in Iranian children and adolescents:
      the Weight Disorders Survey of the CASPIAN-IV study.
AB  - Introduction: This study aims to assess the associated factors of physical
      inactivity among Iranian children and adolescents at national level. The second
      objective is to assess the relationship of physical inactivity with
      anthropometric measures. Methods: Along with a national surveillance program,
      this survey on weight disorders was conducted among a nationally-representative
      sample of Iranian children and adolescents, aged 6-18 years. Students were
      selected by multi-stage cluster sampling from rural and urban areas of 30
      provinces of Iran. The Physical Activity Questionnaire for Adolescents (PAQ-A)
      was used to assess physical activity (PA). Using PAQ-A instrument, PA of past
      week categorized as; low PA level, that included those who scored between 1 to
      1.9 on the PAQ-A instrument and high PA level that included participants with
      estimated scores between 2-5 PAQ-A. Results: Participants were 23183 school
      students (50.8% boys) with a mean age of 12.55 +/- 3.3 years, without significant
      difference in terms of gender. Totally, 23.48% of participants (13.84% of boys
      and 33.42% of girls) were physically inactive. In multivariate logistic
      regression model, with increased age in children and adolescence, the odds of a
      physically inactivity increased (OR: 1.08; 95% CI: 1.07-1.10). The odds of
      prevalence of both obesity and underweight were high in children and adolescents
      with low PA. There was a decreasing trend in PA in higher school grades.
      Conclusion: We found a considerably high prevalence of physical inactivity in
      Iranian children and adolescents, with higher rates among girls and older ages.
      However, we did not find correlation between PA and socioeconomic status (SES).
      Because of the positive relationship between PA and ST, future studies should
      consider the complex interaction of these two items. Multidisciplinary policies
      should be considered in increasing PA programs among children and adolescents.

PMID- 28451089
TI  - The significance of the left atrial volume index in prediction of atrial
      fibrillation recurrence after electrical cardioversion.
AB  - Introduction: Electrical cardioversion (ECV) is a safe method for the treatment
      of atrial fibrillation. It seems that left atrial volume index (LAVI) could be a
      good marker in predicting the success of ECV. The purpose of this study is to
      assess of the significance of LAVI measurement before ECV in predicting the
      recurrence of the AF. Methods: Fifty-one patients with AF, selected for ECV were
      studied in the cardiology department of Tabriz University of medical sciences.
      The clinical and demographic data of all the patients were obtained.
      Echocardiography was performed before and also three months after ECV. Patients
      were separated into two groups: those who maintained SR and those with relapse of
      AF diagnosed by clinical manifestations and electrocardiography (ECG). Results:
      Sinus rhythm (SR) was maintained in 76.5 percent of the patients following the
      three months after ECV. The age, sex and the body mass index (BMI) were not
      significantly different between SR and AF groups. Two groups showed no
      significant differences considering pre-ECV medical history including medications
      and systemic diseases. The initial LAVI of SR group was 42.21+/-12.4 mL/m2 and AF
      group was 96.08+/-52.21 mL/m2, the initial LAVI was significantly different
      between two groups (P = 0.000). The LAVI of SR group decreased significantly
      (5.69+/-0.74 mL/m2) after three months, LAVI decreased from 42.21 +/- 12.4 ml/m2
      to 37.51 +/- 10.52 mL/m2. (P = 0.000). The cut-off point of LAVI value in
      predicting the maintenance of SR was 55 mL/m2. Conclusion: The present study
      indicates that LAVI is a powerful forecaster of the recurrence of AF after ECV.
      The LAVI measurement could be a useful method in the selection of the patients
      with AF for ECV.

PMID- 28451090
TI  - A rare complication of pulmonary tuberculosis - Pulmonary venous thrombosis with
      atrial extension.
AB  - Pulmonary tuberculosis (TB) is serious public health problem in India and
      worldwide. The mortality rate in pulmonary TB is high in those with advanced
      disease and in presence of complications. It presents with wide variety of
      complications of which haematological complications are rare. Many cases were
      reported pulmonary TB associated with deep venous thrombosis, hepatic and portal
      venous thrombosis, central retinal venous thrombosis and sagittal sinus
      thrombosis in TB meningitis. We report a rare case of pulmonary TB with pulmonary
      venous thrombosis and atrial extension. To our best knowledge, this is the first
      case reported of its kind.

PMID- 28451091
TI  - Serum uric acid was an independent predictor of mortality in STsegment elevation
      myocardial infarction patients with Killip I other than Killip II-IV: Comment on
      "J Cardiovasc Thorac Res 2016;8:56-60".

PMID- 28451092
TI  - A computational triage approach to the synthesis of novel difluorocyclopentenes
      and fluorinated cycloheptadienes using thermal rearrangements.
AB  - Electronic structure calculations have been used for the effective triage of
      substituent effects on difluorinated vinylcyclopropane precursors and their
      ability to undergo vinyl cyclopropane rearrangements (VCPR). Groups which
      effectively stabilised radicals, specifically heteroarenes, were found to result
      in the lowest energy barriers. Ten novel precursors were synthesised to test the
      accuracy of computational predictions; the most reactive species which contained
      heteroarenes underwent thermal rearrangements at room temperature to afford novel
      difluorocyclopentenes and fluorinated benzocycloheptadienes through competing
      VCPR and [3,3]-rearrangement pathways, respectively. More controlled
      rearrangement of ethyl 3-(1'(2'2'-difluoro-3'-benzo[d][1,3]dioxol-5
      yl)cyclopropyl)propenoate (22) allowed these competing pathways to be monitored
      at the same time and activation energies for both reactions were determined;
      Ea(VCPR) = (23.4 +/- 0.2) kcal mol-1 and Ea([3,3]) = (24.9 +/- 0.3) kcal mol-1.
      Comparing our calculated activation energies with these parameters showed that no
      single method stood out as the most accurate for predicting barrier heights;
      (U)M05-2X/6-31+G* methodology remained the best for VCPR but M06-2X/6-31G* was
      better for the [3,3]-rearrangement. The consistency observed with (U)B3LYP/6-31G*
      calculations meant that it came closest to a universal method for dealing with
      these systems. The developed computational design model correctly predicted the
      observed selectivity of rearrangement pathways for both our system and literature
      compounds.

PMID- 28451093
TI  - Fabrication of porous nanoflake BiMO x (M = W, V, and Mo) photoanodes via
      hydrothermal anion exchange.
AB  - Most Bi-based photoelectrodes have suitable band gaps and can effectively promote
      the water oxidation reaction. However, simple preparation methods for Bi-based
      binary metal oxides as photoanodes are scarce. This paper describes a simple
      hydrothermal anion exchange method to synthesize Bi-based binary metal oxides
      with controlled morphologies. This synthesis process uses BiOI as the template
      and Bi source, which is eventually converted to Bi-based porous nanoflake
      photoanodes upon reaction with MO x (M = W, V, and Mo)-containing precursors. The
      photoanodes show well-shaped porous nanoflake morphologies and exhibit impressive
      photoelectrochemical properties compared to Bi-based photoanodes synthesized by
      conventional methods. These three samples possess long-term stability under solar
      irradiation and show considerable photocurrent for sulfite oxidation.

PMID- 28451094
TI  - Aromatic "Redox Tag"-assisted Diels-Alder reactions by electrocatalysis.
AB  - Electrocatalysis was employed to promote Diels-Alder reactions between
      electronically mismatched substrates. A catalytic amount of electricity was
      enough to complete the overall reactions and GC-MS monitoring and CV measurements
      clearly illustrated the electrocatalytic nature of the reactions, which involve
      an EC-backward-E mechanism. The electrocatalytic Diels-Alder reactions were
      rationally designed based on the concept of redox tags. The results were
      supported by DFT calculations.

PMID- 28451095
TI  - The chemistry of ZnWO4 nanoparticle formation.
AB  - The need for a change away from classical nucleation and growth models for the
      description of nanoparticle formation is highlighted. By the use of in situ total
      X-ray scattering experiments the transformation of an aqueous polyoxometalate
      precursor mixture to crystalline ZnWO4 nanoparticles under hydrothermal
      conditions was followed. The precursor solution is shown to consist of specific
      Tourne-type sandwich complexes. The formation of pristine ZnWO4 within seconds is
      understood on the basis of local restructuring and three-dimensional reordering
      preceding the emergence of long range order in ZnWO4 nanoparticles. An observed
      temperature dependent trend in defect concentration can be rationalized based on
      the proposed formation mechanism. Following nucleation the individual
      crystallites were found to grow into prolate morphology with elongation along the
      unit cell c-direction. Extensive electron microscopy characterization provided
      evidence for particle growth by oriented attachment; a notion supported by sudden
      particle size increases observed in the in situ total scattering experiments. A
      simple continuous hydrothermal flow method was devised to synthesize highly
      crystalline monoclinic zinc tungstate (ZnWO4) nanoparticles in large scale in
      less than one minute. The present results highlight the profound influence of
      structural similarities in local structure between reactants and final materials
      in determining the specific nucleation of nanostructures and thus explains the
      potential success of a given synthesis procedure in producing nanocrystals. It
      demonstrates the need for abolishing outdated nucleation models, which ignore
      subtle yet highly important system dependent differences in the chemistry of the
      forming nanocrystals.

PMID- 28451096
TI  - Photoredox-mediated Minisci C-H alkylation of N-heteroarenes using boronic acids
      and hypervalent iodine.
AB  - A photoredox-mediated Minisci C-H alkylation reaction of N-heteroarenes with
      alkyl boronic acids is reported. A broad range of primary and secondary alkyl
      groups can be efficiently incorporated into various N-heteroarenes using
      [Ru(bpy)3]Cl2 as photocatalyst and acetoxybenziodoxole as oxidant under mild
      conditions. The reaction exhibits excellent substrate scope and functional group
      tolerance, and offers a broadly applicable method for late-stage
      functionalization of complex substrates. Mechanistic experiments and
      computational studies suggest that an intramolecularly stabilized ortho
      iodobenzoyloxy radical intermediate might play a key role in this reaction
      system.

PMID- 28451097
TI  - Zn...Zn interactions at nickel and palladium centers.
AB  - The analogy between ZnR fragments and the hydrogen radical represents a fruitful
      concept in organometallic synthesis. The organozinc(ii) and -zinc(i) sources
      ZnMe2 (Me = methyl) and [Zn2Cp*2] (Cp* = pentamethylcyclopentadienyl) provide one
      electron fragments .ZnR (R = Me, Cp*), which can be trapped by transition metal
      complexes [L a M], yielding [L b (ZnR) n ]. The addition of the dizinc compound
      [Zn2Cp*2] to coordinatively unsaturated [L a M] by the homolytic cleavage of the
      Zn-Zn bond can be compared to the classic oxidative addition reaction of H2,
      forming dihydride complexes [L a M(H)2]. It has also been widely shown that
      dihydrogen coordinates under preservation of the H-H bond in the case of certain
      electronic properties of the transition metal fragment. The sigma-aromatic
      triangular clusters [Zn3Cp*3]+ and [Zn2CuCp*3] may be regarded as the first
      indication of this so far unknown, side-on coordination mode of [Zn2Cp*2]. With
      this background in mind the question arises if a series of complexes featuring
      the Zn2M structural motif can be prepared exhibiting a (more or less) intact Zn
      Zn interaction, i.e. di-zinc complexes which are analogous to non-classical
      dihydrogen complexes of the Kubas type. In order to probe this idea, a series of
      interrelated organozinc nickel and palladium complexes and clusters were
      synthesized and characterized as model compounds: [Ni(ZnCp*)(ZnMe)(PMe3)3] (1),
      [Ni(ZnCp*)2(ZnMe)2(PMe3)2] (2), [{Ni(CN t Bu)2(MU2-ZnCp*)(MU2-ZnMe)}2] (3),
      [Pd(ZnCp*)4(CN t Bu)2] (4) and [Pd3Zn6(PCy3)2(Cp*)4] (5). The dependence of
      Zn...Zn interactions as a function of the ligand environments and the metal
      centers was studied. Experimental X-ray crystallographic structural data and DFT
      calculations support the analogy between dihydrogen and dizinc transition metal
      complexes.

PMID- 28451098
TI  - Neutral iodotriazoles as scaffolds for stable halogen-bonded assemblies in
      solution.
AB  - The halogen bond (XB) donor properties of neutral 1,4-diaryl-5-iodo-1,2,3
      triazoles are explored using a combination of computational and experimental
      results and are shown to be competitive in halogen bonding efficiency with the
      classic pentafluoroiodobenzene XB donor. The SNAr reactivity of these donors
      permits the facile assembly of an iodotriazole functionalised with a 3
      oxypyridine XB acceptor, thus generating a molecular scaffold capable of
      undergoing dimerisation through the formation of two halogen bonds. The formation
      of this halogen-bonded dimer is demonstrated by 1H and DOSY NMR experiments and a
      plausible structure generated using DFT calculations.

PMID- 28451099
TI  - Scandium-catalysed intermolecular hydroaminoalkylation of olefins with aliphatic
      tertiary amines.
AB  - A homoleptic scandium trialkyl complex in combination with a borate compound
      served as an excellent catalyst for the C-H addition of aliphatic tertiary amines
      to olefins. This highly regiospecific, 100% atom efficient C-H bond alkylation
      reaction was applicable to a wide variety of tertiary amines and olefins,
      including functionalised styrenes and unactivated alpha-olefins. This work
      represents the first example of rare-earth catalysed olefin hydroaminoalkylation
      and also the first example of catalytic C-H addition of aliphatic tertiary amines
      to olefins with any catalyst.

PMID- 28451100
TI  - Non-covalent S...O interactions control conformation in a scaffold that disrupts
      islet amyloid polypeptide fibrillation.
AB  - Conformationally-constrained molecules that selectively recognise the surfaces of
      proteins have the potential to direct the path of protein folding. Such molecules
      are of therapeutic interest because the misfolding of proteins, especially that
      which results in fibrillation and aggregation, is strongly correlated with
      numerous diseases. Here we report the novel use of S...O interactions as a
      conformational control element in a new class of non-peptidic scaffold that
      mimics key elements of protein surfaces. These molecules disrupt the fibrillation
      of islet amyloid polypeptide (IAPP), a process that is implicated in the
      pathology of type II diabetes.

PMID- 28451101
TI  - Atmospheric-pressure ionization and fragmentation of peptides by solution-cathode
      glow discharge.
AB  - Modern "-omics" (e.g., proteomics, glycomics, metabolomics, etc.) analyses rely
      heavily on electrospray ionization and tandem mass spectrometry to determine the
      structural identity of target species. Unfortunately, these methods are limited
      to specialized mass spectrometry instrumentation. Here, a novel approach is
      described that enables ionization and controlled, tunable fragmentation of
      peptides at atmospheric pressure. In the new source, a direct-current plasma is
      sustained between a tapered metal rod and a flowing sample-containing solution.
      As the liquid stream contacts the electrical discharge, peptides from the
      solution are volatilized, ionized, and fragmented. At high discharge currents
      (e.g., 70 mA), electrospray-like spectra are observed, dominated by singly and
      doubly protonated molecular ions. At lower currents (35 mA), many peptides
      exhibit extensive fragmentation, with a-, b-, c-, x-, and y-type ion series
      present as well as complex fragments, such as d-type ions, not previously
      observed with atmospheric-pressure dissociation. Though the mechanism of
      fragmentation is currently unclear, observations indicate it could result from
      the interaction of peptides with gas-phase radicals or ultraviolet radiation
      generated within the plasma.

PMID- 28451102
TI  - Electrocatalytic amplification of DNA-modified nanoparticle collisions via
      enzymatic digestion.
AB  - We report a new and general approach that will be useful for adapting the method
      of electrocatalytic amplification (ECA) to biosensing applications. In ECA,
      individual collisions of catalytic nanoparticles with a noncatalytic electrode
      surface lead to bursts of current. In the work described here, the current arises
      from catalytic electrooxidation of N2H4 at the surface of platinum nanoparticles
      (PtNPs). The problem with using ECA for biosensing applications heretofore, is
      that it is necessary to immobilize a receptor, such as DNA (as in the case here)
      or an antibody on the PtNP surface. This inactivates the colliding NP, however,
      and leads to very small collision signatures. In the present article, we show
      that single-stranded DNA (ssDNA) present on the PtNP surface can be detected by
      selectively removing a fraction of the ssDNA using the enzyme Exonuclease I (Exo
      I). About half of the current associated with collisions of naked PtNPs can be
      recovered from fully passivated PtNPs after exposure to Exo I. Experiments
      carried out using both Au and Hg ultramicroelectrodes reveal some mechanistic
      aspects of the collision process before and after treatment of the ssDNA-modified
      PtNPs with Exo I.

PMID- 28451103
TI  - Measuring the oxygen content of a single oil droplet.
AB  - Using toluene droplets as a model for artificial oxygen carriers, the real-time
      measurement of attomole oxygen contents at the individual droplet level is
      reported for the first time. Oxygen reduction is observed within single
      individual toluene droplets when they impact with an electrode held at a suitable
      potential. The oxygen content within single toluene droplets is quantified by
      referencing the reductive charge from oxygen reduction to the charge from
      oxidation of a ferrocene filled toluene droplet of known concentration.

PMID- 28451105
TI  - Conducting polymer PPy nanowire-based triboelectric nanogenerator and its
      application for self-powered electrochemical cathodic protection.
AB  - As a new type of energy harvesting device, the triboelectric nanogenerator (TENG)
      can convert almost all kinds of mechanical energy into electricity based on the
      coupling of triboelectrification and electrostatic induction. Here, a novel TENG
      is constructed with a conducting polymer polypyrrole nanowire (PPy NW) electrode,
      which is prepared by an electrochemical polymerization method with anodic
      aluminum oxide (AAO) as the template. The PPy NW-based TENG shows high output
      performance with a maximum short circuit current density of 23.4 mA m-2 and
      output voltage of 351 V, which can light 372 commercial red LEDs. Moreover, a
      self-powered anticorrosion system powered by the PPy NW-based TENG is designed,
      which can provide extra electrons to inject into the surface of the protected
      metals, forming effective impressed current cathodic protection by harvesting
      mechanical energy or wind energy. This smart device has potential applications
      for protecting metals from corrosion in daily life, industrial production and
      ocean exploration by harvesting the energies in the ambient environment.

PMID- 28451104
TI  - Interaction of methanol with the oxygen-evolving complex: atomistic models,
      channel identification, species dependence, and mechanistic implications.
AB  - Methanol has long being used as a substrate analogue to probe access pathways and
      investigate water delivery at the oxygen-evolving complex (OEC) of photosystem
      II. In this contribution we study the interaction of methanol with the OEC by
      assembling available spectroscopic data into a quantum mechanical treatment that
      takes into account the local channel architecture of the active site. The effect
      on the magnetic energy levels of the Mn4Ca cluster in the S2 state of the
      catalytic cycle can be explained equally well by two models that involve either
      methanol binding to the calcium ion of the cluster, or a second-sphere
      interaction in the vicinity of the "dangler" Mn4 ion. However, consideration of
      the latest 13C hyperfine interaction data shows that only one model is fully
      consistent with experiment. In contrast to previous hypotheses, methanol is not a
      direct ligand to the OEC, but is situated at the end-point of a water channel
      associated with the O4 bridge. Its effect on magnetic properties of plant PS-II
      results from disruption of hydrogen bonding between O4 and proximal channel water
      molecules, thus enhancing superexchange (antiferromagnetic coupling) between the
      Mn3 and Mn4 ions. The same interaction mode applies to the dark-stable S1 state
      and possibly to all other states of the complex. Comparison of protein sequences
      from cyanobacteria and plants reveals a channel-altering substitution (D1-Asn87
      versus D1-Ala87) in the proximity of the methanol binding pocket, explaining the
      species-dependence of the methanol effect. The water channel established as the
      methanol access pathway is the same that delivers ammonia to the Mn4 ion,
      supporting the notion that this is the only directly solvent-accessible manganese
      site of the OEC. The results support the pivot mechanism for water binding at a
      component of the S3 state and would be consistent with partial inhibition of
      water delivery by methanol. Mechanistic implications for enzymatic regulation and
      catalytic progression are discussed.

PMID- 28451106
TI  - Molecular basis for functional switching of GFP by two disparate non-native post
      translational modifications of a phenyl azide reaction handle.
AB  - Through the genetic incorporation of a single phenyl azide group into superfolder
      GFP (sfGFP) at residue 148 we provide a molecular description of how this highly
      versatile chemical handle can be used to positively switch protein function in
      vitro and in vivo via either photochemistry or bioconjugation. Replacement of
      H148 with p-azido-l-phenylalanine (azF) blue shifts the major excitation peak ~90
      nm by disrupting the H-bond and proton transfer network that defines the
      chromophore charged state. Bioorthogonal click modification with a simple
      dibenzylcyclooctyne or UV irradiation shifts the neutral-anionic chromophore
      equilibrium, switching fluorescence to the optimal ~490 nm excitation. Click
      modification also improved quantum yield over both the unmodified and original
      protein. Crystal structures of both the click modified and photochemically
      converted forms show that functional switching is due to local conformational
      changes that optimise the interaction networks surrounding the chromophore.
      Crystal structure and mass spectrometry studies of the irradiated protein suggest
      that the phenyl azide converts to a dehydroazepine and/or an azepinone. Thus,
      protein embedded phenyl azides can be used beyond simple photocrosslinkers and
      passive conjugation handles, and mimic many natural post-translational
      modifications: modulation though changes in interaction networks.

PMID- 28451107
TI  - The dual capture of AsV and AsIII by UiO-66 and analogues.
AB  - UiO-66 and analogues were successfully tailored to chemoselectively capture AsV
      oxyanions at the hydroxylated node and neutral AsIII species with the thiolated
      organic linkers. More efficient and faster uptake can be achieved with increasing
      defect densities, increasing pore aperture sizes, and decreasing particle sizes.

PMID- 28451108
TI  - Self-sorted photoconductive xerogels.
AB  - We show that a perylene bisimide (PBI)-based gelator forms self-sorted mixtures
      with a stilbene-based gelator. To form the self-sorted gels, we use a slow pH
      change induced by the hydrolysis of glucono-delta-lactone (GdL) to gluconic acid.
      We prove that self-sorting occurs using NMR spectroscopy, UV-Vis spectroscopy,
      rheology, and viscometry. The corresponding xerogels are photoconductive.
      Importantly, the wavelength dependence of the photoconductive films is different
      to that of the films formed from the perylene bisimide alone. Transient
      absorption spectroscopy of the xerogels reveals changes in the spectrum of the
      PBI on the picosecond timescale in the presence of stilbene with a PBI radical
      anion being formed within 10 ps when the stilbene is present. The ability to form
      the PBI radical anion under visible light leads to the enhanced spectral response
      of the multicomponent gels. These systems therefore have potential as useful
      visible-active optoelectronics.

PMID- 28451109
TI  - A concerted two-prong approach to the in situ allosteric regulation of
      bifunctional catalysis.
AB  - Herein, we report the reversible in situ "on-off" allosteric regulation of
      hydrogen-bond-donating (HBD)-Lewis base co-catalytic activity via a concerted two
      prong methodology entailing cooperative acid-base chemistry and a structurally
      addressable coordination complex. Specifically, a heteroligated Pt(ii) weak-link
      approach (WLA) tweezer complex containing both a hemilabile squaramide-piperidine
      based catalytic ligand and a sodium sulfonate hydrogen-bond-accepting (HBA)
      ligand was synthesized. Due to the hemilabile nature of the catalyst-containing
      ligand, the heteroligated complex can be reversibly toggled in situ between a
      flexible, semi-open state and a rigid, fully closed state upon the addition of
      elemental ion cues. 1H NMR spectroscopy titration studies show that in the semi
      open state interligand hydrogen-bonding prevents substrate recognition by the
      squaramide unit, while in the fully closed state ligand-ligand interactions are
      prevented. This results in a catalytically active closed state, whereas in the
      semi-open state, when the piperidine tertiary amine is deliberately protonated,
      no catalytic activity is observed. Reversible interconversion between the active
      fully closed state and the dormant protonated semi-open state is achieved in the
      presence of substrate upon the concerted addition and abstraction of both a
      proton and a coordinating elemental anion. In this work, allosteric regulation of
      catalytic activity is demonstrated for both the Michael addition of nitroethane
      to beta-nitrostyrene and the ring-opening of l-(-)-lactide. Taken together, this
      work details a potentially generalizable platform for the "on-off" allosteric
      regulation of a family of HBD-Lewis base co-catalysts capable of catalyzing a
      broad scope of reactions, including the living ring-opening polymerization of
      cyclic esters.

PMID- 28451110
TI  - Mass spectrometric snapshots for electrochemical reactions.
AB  - A hybrid ultramicroelectrode containing one micro-carbon electrode and one empty
      micro-channel was employed to be a micro-electrochemical cell and a mass
      spectrometric nanospray emitter. This setup can combine MS with an electrode
      directly and provide in situ information about an electrochemical reaction. The
      mechanisms proposed by Bard et al. for a Ru(bpy)32+ (bpy = 2,2'-bipyridine)
      electrochemiluminescence (ECL) system were confirmed by the MS detection of key
      intermediates. The short-lived diimine intermediate of electrochemical oxidation
      of uric acid was also detected, which affirms that the novel technique is able to
      catch fleeting intermediates. These experimental results demonstrate that this
      new method is simple, easy to implement and can be coupled with many commercial
      mass spectrometric instruments to provide very useful information about
      electrochemical reactions.

PMID- 28451111
TI  - Dynamic propeller conformation for the unprecedentedly high degree of chiral
      amplification of supramolecular helices.
AB  - An unprecedentedly high degree of chiral amplification of supramolecular helices
      in a sergeants and soldiers system was realized using a propeller-shaped
      molecule, triphenylamine (TPA), as the monomer. One sergeant controlled the
      handedness of 500 soldiers in supramolecular helices. We further demonstrated
      that a TPA derivative could switch its role from sergeant to soldier and vice
      versa depending on its partners. These achievements could be realized using the
      dynamic propeller conformation of TPA and provide new insights into
      supramolecular assemblies and the supramolecular chiral amplification of helices.

PMID- 28451112
TI  - Polydopamine coated manganese oxide nanoparticles with ultrahigh relaxivity as
      nanotheranostic agents for magnetic resonance imaging guided synergetic chemo
      /photothermal therapy.
AB  - Mn-based nanoparticles have been regarded as a new class of probes for magnetic
      resonance imaging (MRI), but their low relaxivity is the major obstacle for
      applications in vivo. Herein, we designed and constructed a multifunctional
      nanotheranostic (FA-Mn3O4@PDA@PEG) for MRI guided combinatorial chemo
      /photothermal therapy (PTT) for cancer. The ultrahigh relaxivity of 14.47 mM-1 s
      1 makes the nanotheranostic an excellent contrast agent for MRI in vitro and in
      vivo, and provides comprehensive information for tumor diagnosis. When irradiated
      with an 808 nm NIR laser, FA-Mn3O4@PDA@PEG exhibits a remarkably improved and
      synergistic therapeutic effect compared to PTT or chemotherapy alone, providing
      high therapeutic efficiency and low side effects of drugs. These findings are of
      great interest and will inspire us to develop highly effective MRI guided
      synergetic chemo-/photothermal therapy for cancer treatment.

PMID- 28451113
TI  - Biazulene diimides: a new building block for organic electronic materials.
AB  - Azulene, a 10-pi-electron isomer of naphthalene, is a nonbenzenoid bicyclic
      aromatic hydrocarbon with a beautiful blue color and a large dipole moment. We
      present here the first class of azulene-based aromatic diimides, 2,2'-biazulene
      1,1',3,3'-tetracarboxylic diimides (BAzDIs), which comprise a 2,2'-biazulene
      moiety and two seven-membered imide groups. DFT calculations, thermal, optical
      and electrochemical properties of two BAzDI derivatives as well as single crystal
      analysis and the charge transport behavior were studied. The results demonstrate
      that BAzDIs have unique photophysical properties and are promising for organic
      electronic materials.

PMID- 28451114
TI  - Dual n-type units including pyridine and diphenylphosphine oxide: effective
      design strategy of host materials for high-performance organic light-emitting
      diodes.
AB  - By using pyridine and diphenylphosphine oxide (DPPO) as dual n-type units, two
      novel bipolar hosts, namely (5-(3,5-di(9H-carbazol-9-yl)phenyl)pyridin-3
      yl)diphenylphosphine oxide (m-PyPOmCP), and (6-(3,5-di(9H-carbazol-9
      yl)phenyl)pyridin-3-yl)diphenylphosphine oxide (p-PyPOmCP) are developed for blue
      and green phosphorescent organic light-emitting diodes (PhOLEDs). Direct linking
      of the dual n-type units not only pulls the LUMOs down, but also keeps the HOMO
      levels shallow, and leads to high triplet energies (2.78-2.86 eV) and small
      singlet-triplet energy differences (0.23-0.35 eV). Blue and green PhOLEDs are
      fabricated using FIrpic and Ir(ppy)3 as dopants in the hosts. A low turn-on
      voltage of 2.6 V is achieved for the green PhOLEDs. The m-PyPOmCP hosted blue
      PhOLED achieves a high current efficiency of 55.6 cd A-1 (corresponding to a
      maximum external quantum efficiency of 25.3% and a power efficiency of 43.6 lm W
      1). The p-PyPOmCP hosted green PhOLED exhibits an efficiency of 98.2 cd A-1
      (28.2% and 102.8 lm W-1). These data are among the best values for blue and green
      PhOLEDs reported so far. These "dual n-type units" hosts show much better
      performance than their DPPO-free analogue, clearly proving that the direct
      linking of DPPO and pyridine as dual n-type units is an effective molecular
      design strategy for host materials for use in high-performance PhOLEDs.

PMID- 28451115
TI  - Stretchable supramolecular hydrogels with triple shape memory effect.
AB  - Shape memory polymers based on reversible supramolecular interactions have
      invoked growing research interest, but still suffer from limitations such as poor
      mechanical strength and finite shape memory performance. Here, we present a novel
      mechanical stretchable supramolecular hydrogel with a triple shape memory effect
      at the macro/micro scale. The introduction of a double network concept into
      supramolecular shape memory hydrogels endows them with excellent mechanical
      properties. The design of two non-interfering supramolecular interaction systems
      of both dynamic phenylboronic (PBA)-diol ester bonds and the chelation of
      alginate with Ca2+ endues the hydrogel with outstanding triple shape memory
      functionalities.

PMID- 28451116
TI  - Self-powered fluorescence display devices based on a fast self
      charging/recharging battery (Mg/Prussian blue).
AB  - Stimuli-responsive (such as voltage and/or light) fluorescence display systems
      have attracted particular attention in their promising fields of application.
      However, there are few examples of self-powered fluorescence display devices.
      Here we designed and fabricated a self-powered fluorescence display device based
      on a fast-charging/recharging battery. The specially designed battery was
      composed of a Prussian blue (PB) cathode and a magnesium metal anode with a high
      theoretical redox potential difference (~2.8 V). Moreover, smartly adding a trace
      amount of NaClO in the electrolyte could realize oxidizing PW to PB ~480 times
      faster than when oxidizing without NaClO, leading to the fast self-charging and
      high power density (maximum power density of 13.34 mW cm-2, about two to three
      orders of magnitude larger than previous bio-fuel cells) of the Mg/PB battery.
      Most importantly, PB was used as not only the cathodic catalyst but also as an
      electrochromic material, making it possible to construct a self-powered and
      rechargeable electrochromic fluorescence display with only two electrodes.
      Besides, fluorescent [Ru(bpy)3]2+-doped silica nanoparticles (Ru@SiO2), were
      selected as the fluorescence resonance energy transfer (FRET) donor to match PB
      (FRET acceptor). To the best of our knowledge, we demonstrated a self-powered and
      rechargeable electrochromic fluorescence display with only two electrodes for the
      first time.

PMID- 28451117
TI  - Rhenium(i) trinuclear rings as highly efficient redox photosensitizers for
      photocatalytic CO2 reduction.
AB  - We developed new cyclic Re(i)-based trinuclear redox photosensitizers with both
      high oxidation power in the excited state and strong reduction power in the
      reduced form. These excellent properties were achieved by introducing electron
      donating groups on the diimine ligand of the Re(i) metal centre and by connecting
      each Re(i) unit with polyphenyl-bisphosphine bridging ligands. These Re-rings
      were applied to homogenous visible light-driven photocatalytic CO2 reduction in
      conjunction with various mononuclear catalysts, such as Re(i), Ru(ii) and Mn(i)
      metal complexes, employing a relatively weak sacrificial electron donor,
      triethanolamine. Each system showed good product selectivity (CO or HCOOH) and an
      excellent quantum yield of product formation PhiCO = 0.60 to 0.74 using fac
      [ReI(bpy)(CO)3(CH3CN)]+, PhiHCOOH = 0.58 using trans(Cl)-RuII(dtbb)(CO)2Cl2 and
      PhiHCOOH = 0.48 using a fac-[MnI(dtbb)(CO)3(CH3CN)]+ catalyst. The high
      photocatalytic efficiencies for CO2 reduction are attributed to efficient
      reductive quenching of the Re-ring by triethanolamine and fast electron transfer
      from the generated one-electron-reduced species of the ring to the catalyst.

PMID- 28451118
TI  - Visible light mediated metal-free thiol-yne click reaction.
AB  - The carbon-sulfur bond formation reaction is of paramount importance for
      functionalized materials design, as well as for biochemical applications. The use
      of expensive metal-based catalysts and the consequent contamination with trace
      metal impurities are challenging drawbacks of the existing methodologies. Here,
      we describe the first environmentally friendly metal-free photoredox pathway to
      the thiol-yne click reaction. Using Eosin Y as a cheap and readily available
      catalyst, C-S coupling products were obtained in high yields (up to 91%) and
      excellent selectivity (up to 60 : 1). A 3D-printed photoreactor was developed to
      create arrays of parallel reactions with temperature stabilization to improve the
      performance of the catalytic system.

PMID- 28451119
TI  - Vibrational spectroscopy reveals the initial steps of biological hydrogen
      evolution.
AB  - [FeFe] hydrogenases are biocatalytic model systems for the exploitation and
      investigation of catalytic hydrogen evolution. Here, we used vibrational
      spectroscopic techniques to characterize, in detail, redox transformations of the
      [FeFe] and [4Fe4S] sub-sites of the catalytic centre (H-cluster) in a monomeric
      [FeFe] hydrogenase. Through the application of low-temperature resonance Raman
      spectroscopy, we discovered a novel metastable intermediate that is characterized
      by an oxidized [FeIFeII] centre and a reduced [4Fe4S]1+ cluster. Based on this
      unusual configuration, this species is assigned to the first, deprotonated H
      cluster intermediate of the [FeFe] hydrogenase catalytic cycle. Providing
      insights into the sequence of initial reaction steps, the identification of this
      species represents a key finding towards the mechanistic understanding of
      biological hydrogen evolution.

PMID- 28451120
TI  - Total chemical synthesis of proteins without HPLC purification.
AB  - The total chemical synthesis of proteins is a tedious and time-consuming
      endeavour. The typical steps involve solid phase synthesis of peptide thioesters
      and cysteinyl peptides, native chemical ligation (NCL) in solution,
      desulfurization or removal of ligation auxiliaries in the case of extended NCL as
      well as many intermediary and final HPLC purification steps. With an aim to
      facilitate and improve the throughput of protein synthesis we developed the first
      method for the rapid chemical total on-resin synthesis of proteins that proceeds
      without a single HPLC-purification step. The method relies on the combination of
      three orthogonal protein tags that allow sequential immobilization (via the N
      terminal and C-terminal ends), extended native chemical ligation and release
      reactions. The peptide fragments to be ligated are prepared by conventional solid
      phase synthesis and used as crude materials in the subsequent steps. An N
      terminal His6 unit permits selective immobilization of the full length peptide
      thioester onto Ni-NTA agarose beads. The C-terminal peptide fragment carries a C
      terminal peptide hydrazide and an N-terminal 2-mercapto-2-phenyl-ethyl ligation
      auxiliary, which serves as a reactivity tag for the full length peptide. As a
      result, only full length peptides, not truncation products, react in the
      subsequent on-bead extended NCL. After auxiliary removal the ligation product is
      liberated into solution upon treatment with mild acid, and is concomitantly
      captured by an aldehyde-modified resin. This step allows the removal of the most
      frequently observed by-product in NCL chemistry, i.e. the hydrolysed peptide
      thioester (which does not contain a C-terminal peptide hydrazide). Finally, the
      target protein is released with diluted hydrazine or acid. We applied the method
      in the synthesis of 46 to 126 amino acid long MUC1 proteins comprising 2-6 copies
      of a 20mer tandem repeat sequence. Only three days were required for the parallel
      synthesis of 9 MUC1 proteins which were obtained in 8-33% overall yield with 90
      98% purity despite the omission of HPLC purification.

PMID- 28451121
TI  - Tantalum nitride films integrated with transparent conductive oxide substrates
      via atomic layer deposition for photoelectrochemical water splitting.
AB  - Tantalum nitride, Ta3N5, is one of the most promising materials for solar energy
      driven water oxidation. One significant challenge of this material is the high
      temperature and long duration of ammonolysis previously required to synthesize
      it, which has so far prevented the use of transparent conductive oxide (TCO)
      substrates to be used which would allow sub-bandgap light to be transmitted to a
      photocathode. Here, we overcome this challenge by utilizing atomic layer
      deposition (ALD) to directly deposit tantalum oxynitride thin films, which can be
      fully converted to Ta3N5via ammonolysis at 750  degrees C for 30 minutes. This
      synthesis employs far more moderate conditions than previous reports of efficient
      Ta3N5 photoanodes. Further, we report the first ALD of Ta-doped TiO2 which we
      show is a viable TCO material that is stable under the relatively mild
      ammonolysis conditions employed. As a result, we report the first example of a
      Ta3N5 electrode deposited on a TCO substrate, and the photoelectrochemical
      behavior. These results open the door to achieve efficient overall water
      splitting using a Ta3N5 photoanode.

PMID- 28451122
TI  - Fluorinated antimony(v) derivatives: strong Lewis acidic properties and
      application to the complexation of formaldehyde in aqueous solutions.
AB  - As part of our ongoing studies of water tolerant Lewis acids, we have synthesized
      and investigated the properties of Sb(C6F5)3(O2C6Cl4), a fluorinated stiborane
      whose Lewis acidity approaches that of B(C6F5)3. While chloroform solutions of
      this Lewis acid can be kept open to air or exposed to water for extended periods
      of time, this new Lewis acid reacts with P t Bu3 and paraformaldehyde to form the
      corresponding formaldehyde adduct t Bu3P-CH2-O-Sb(C6F5)3(O2C6Cl4). To test if
      this reactivity can also be observed with systems that combine the phosphine and
      the stiborane within the same molecule, we have also prepared o
      C6H4(PPh2)(SbAr2(O2C6Cl4)) (Ar = Ph, C6F5). These yellow compounds, which possess
      an intramolecular P->Sb interaction, are remarkably inert to water but do,
      nonetheless, react with and accomodate formaldehyde into the P/Sb pocket. In the
      case of the fluorinated derivative o-C6H4(PPh2)(Sb(C6F5)2(O2C6Cl4)), formaldehyde
      complexation, which occurs in water/dichloromethane biphasic mixtures, is
      accompanied by a colourimetric turn-off response thus highlighting the potential
      that this chemistry holds in the domain of molecular sensing.

PMID- 28451123
TI  - Ultrahigh affinity Raman probe for targeted live cell imaging of prostate cancer.
AB  - Precise visualization of tumor margins with characterization of microscopic tumor
      invasion are unmet needs in prostate oncology that demand approaches with high
      sensitivity and specificity. To address those needs we report surface-enhanced
      Raman scattering (SERS) based optical imaging for prostate cancer using a
      combination of live cell Raman microscopy, optimally engineered SERS tags and a
      urea-based small-molecule inhibitor of prostate-specific membrane antigen (PSMA)
      as a targeting moiety. We develop gold nanostar based SERS agents that offer
      ultrahigh binding affinity to PSMA with nearly four orders of magnitude lower
      IC50 values in relation to existing clinical imaging agents. This combination
      enables selective recognition of prostate cancer cells, and facilitates
      quantitative and photostable Raman measurements. Using Raman microscopy to
      analyze phenotypically similar prostate cancer cell lines differing only in PSMA
      expression, we demonstrate facile, site-selective recognition using as low as 20
      pM of the SERS agent for imaging, opening the door for spectroscopic detection of
      prostate and other PSMA-expressing tumors in vivo.

PMID- 28451124
TI  - Perylene bisimide hydrogels and lyotropic liquid crystals with temperature
      responsive color change.
AB  - The self-assembly of perylene bisimide (PBI) dyes bearing oligo ethylene glycol
      (OEG) units in water affords responsive functional nanostructures characterized
      by their lower critical solution temperature (LCST). Tuning of the LCST is
      realized by a supramolecular approach that relies on two structurally closely
      related PBI-OEG molecules. The two PBIs socially co-assemble in water and the
      resulting nanostructures exhibit a single LCST in between the transition
      temperatures of the aggregates formed by single components. This permits to
      precisely tune the transition from a hydrogel to a lyotropic liquid crystal state
      at temperatures between 26 and 51  degrees C by adjusting the molar fraction of
      the two PBIs. Owing to concomitant changes in PBI-PBI interactions this phase
      transition affords a pronounced color change with "fluorescence-on" response that
      can be utilized as a smart temperature sensory system.

PMID- 28451125
TI  - Structure-property study of cross-linked hydrocarbon/poly(ethylene oxide)
      electrolytes with superior conductivity and dendrite resistance.
AB  - Lithium dendrite growth is a fundamental problem that precludes the practical use
      of lithium metal batteries. Solid polymer electrolytes (SPEs) have been widely
      studied to resist the growth of lithium dendrites but the underlying mechanisms
      are still unclear. Most SPEs sacrifice high ionic conductivities for increased
      dendrite suppression performance by using components with high mechanical
      stiffness. We report a class of cross-linked hydrocarbon/poly(ethylene oxide)
      SPEs with both high ionic conductivities (approaching 1 * 10-3 S cm-1 at 25 
      degrees C) and superior dendrite suppression characteristics. A systematic
      structure-property study shows that the crystallinity of the hydrocarbon
      backbones plays a key role in regulating size and morphology of lithium
      dendrites, as well as the ability to suppress their growth.

PMID- 28451126
TI  - Specific inhibition of CK2alpha from an anchor outside the active site.
AB  - The development of selective inhibitors of protein kinases is challenging because
      of the significant conservation of the ATP binding site. Here, we describe a new
      mechanism by which the protein kinase CK2alpha can be selectively inhibited using
      features outside the ATP site. We have identified a new binding site for small
      molecules on CK2alpha adjacent to the ATP site and behind the alphaD loop, termed
      the alphaD pocket. An elaborated fragment anchored in this site has been linked
      with a low affinity fragment binding in the ATP site, creating a novel and
      selective inhibitor (CAM4066) that binds CK2alpha with a Kd of 320 nM and shows
      significantly improved selectivity compared to other CK2alpha inhibitors. CAM4066
      shows target engagement in several cell lines and similar potency to clinical
      trial candidate CX4945. Our data demonstrate that targeting a poorly conserved,
      cryptic pocket allows inhibition of CK2alpha via a novel mechanism, enabling the
      development of a new generation of selective CK2alpha inhibitors.

PMID- 28451127
TI  - Cubic three-dimensional hybrid silica solids for nuclear hyperpolarization.
AB  - Hyperpolarization of metabolites by dissolution dynamic nuclear polarization (D
      DNP) for MRI applications often requires fast and efficient removal of the
      radicals (polarizing agents). Ordered mesoporous SBA-15 silica materials
      containing homogeneously dispersed radicals, referred to as HYperPolarizing
      SOlids (HYPSOs), enable high polarization - P(1H) = 50% at 1.2 K - and
      straightforward separation of the polarizing HYPSO material from the
      hyperpolarized solution by filtration. However, the one-dimensional tubular pores
      of SBA-15 type materials are not ideal for nuclear spin diffusion, which may
      limit efficient polarization. Here, we develop a generation of hyperpolarizing
      solids based on a SBA-16 structure with a network of pores interconnected in
      three dimensions, which allows a significant increase of polarization, i.e. P(1H)
      = 63% at 1.2 K. This result illustrates how one can improve materials by
      combining a control of the incorporation of radicals with a better design of the
      porous network structures.

PMID- 28451128
TI  - Square channels formed by a peptide derived from transthyretin.
AB  - High-resolution structures of peptide supramolecular assemblies are key to
      understanding amyloid diseases and designing peptide-based materials. This paper
      explores the supramolecular assembly of a macrocyclic beta-sheet peptide derived
      from transthyretin (TTR). The peptide mimics the beta-hairpin formed by the beta
      strands G and H of TTR, which form the interface of the TTR tetramer. X-ray
      crystallography reveals that the peptide does not form a tetramer, but rather
      assembles to form square channels. The square channels are formed by extended
      networks of beta-sheets and pack in a "tilted windows" pattern. This unexpected
      structure represents an emergent property of the peptide and broadens the scope
      of known supramolecular assemblies of beta-sheets.

PMID- 28451129
TI  - Exploring template-bound dinuclear copper porphyrin nanorings by EPR
      spectroscopy.
AB  - Electron paramagnetic resonance (EPR) spectroscopy has been used to study the
      molecular geometry as well as metal-ligand interactions in ten-membered porphyrin
      nanorings ( c-P10Cu2 ) containing two copper and eight zinc centers. The presence
      of copper in the structures allows intramolecular interactions, including dipolar
      interactions between electron spins and hyperfine interactions to be quantified.
      Results obtained for c-P10Cu2 samples bound to two molecular templates with four
      or five binding sites, respectively, are compared to those obtained for a sample
      of the porphyrin ring in the absence of any templates. It is shown that the
      observed lower binding affinity of the nitrogen ligand to copper as compared to
      zinc has a strong impact on the geometries of the respective template-bound c
      P10Cu2 structures. The interaction between the central copper atom and nitrogen
      ligands is weak, but pulsed EPR hyperfine techniques such as ENDOR and HYSCORE
      are very sensitive to this interaction. Upon binding of a nitrogen ligand to
      copper, the hyperfine couplings of the in-plane nitrogen atoms of the porphyrin
      core are reduced by about 3 MHz. In addition, the copper hyperfine couplings as
      well as the g-factors are altered, as detected by continuous wave EPR. DFT
      calculations of the hyperfine coupling tensors support the assignment of the
      measured couplings to the nuclei within the structure and reproduce the
      experimentally observed trends. Finally, Double Electron Electron Resonance
      (DEER) is used to measure the distances between the copper centers in a range
      between 2.5 and 5 nm, revealing the preferred geometries of the template-bound
      nanorings.

PMID- 28451130
TI  - Nanorings with copper(ii) and zinc(ii) centers: forcing copper porphyrins to bind
      axial ligands in heterometallated oligomers.
AB  - The affinity of copper(ii) porphyrins for pyridine ligands is extremely weak, but
      oligo-pyridine templates can be used to direct the synthesis of Cu-containing
      cyclic porphyrin oligomers when they also have Zn centers. We report the
      synthesis of two heterometallated nanorings: a six-porphyrin ring prepared from a
      Zn/Cu/Zn linear trimer and a ten-porphyrin ring prepared from a Zn/Zn/Cu/Zn/Zn
      pentamer. Both these macrocycles have copper porphyrins at two specific positions
      across the diameter of the ring and zinc at other sites. The presence of a
      paramagnetic metal results in broadening of the 1H NMR spectra and reduces the
      relaxation time constants (T1 and T2). The changes in T1 provide quantitative
      information on the distance of each proton from the copper atom. The
      Zn/Zn/Cu/Zn/Zn linear porphyrin pentamer binds strongly to a penta-pyridyl
      template, despite the weakness of the Cu-N interaction, because of the chelate
      cooperativity of the neighboring Zn-N coordination. The stabilities of a family
      of four linear porphyrin pentamer complexes were determined by UV-vis-NIR
      titration and analyzed using a chemical double-mutant cycle. The results show
      that the free energy of interaction of a copper center to axial pyridine ligands
      is -6.2 kJ mol-1 when the entropy cost of bringing together the two molecules has
      already been paid by pyridine-zinc interactions. The development of template
      directed approaches to the synthesis of nanorings with combinations of different
      metals at specific positions around the ring opens up many possibilities for
      controlling the photophysical behavior of these supramolecular systems and for
      probing their conformations by EPR.

PMID- 28451131
TI  - Coupling two enzymes into a tandem nanoreactor utilizing a hierarchically
      structured MOF.
AB  - A hierarchical porous metal-organic framework (MOF), PCN-888, containing three
      types of cavities was utilized to couple two enzymes into a tandem nanoreactor.
      The largest cavity (6.2 nm) can only accommodate one molecule of glucose oxidase
      (GOx). The intermediate cavity (5.0 nm) can accommodate one and only one molecule
      of horseradish peroxidase (HRP). The small cavity (2.0 nm) has sufficient size
      for neither GOx nor HRP, and remains open as a substrate diffusion pathway. The
      coupling of the two enzymes can only be achieved through a unique stepwise
      encapsulation with a specific order (GOx first, followed by HRP). The tandem
      nanoreactor shows excellent catalytic performances and negligible enzyme
      leaching. Its catalytic activity is well maintained within several catalytic
      cycles. Moreover, PCN-888 can provide protection to the encapsulated enzymes
      against trypsin digestion, indicating the in vitro and in vivo stability of the
      nanoreactor.

PMID- 28451132
TI  - Electrochemically tuneable multi-colour electrochemiluminescence using a single
      emitter.
AB  - A single starting component electrochemiluminescence system from which red,
      green, blue or white emission can be obtained, depending on the applied potential
      or the mode of the ECL experiment, is described. The convoluted ECL spectral
      responses observed at different potentials are readily explained using a 3D-ECL
      technique, where the ECL spectral profile is continuously monitored as a function
      of potential during voltammetric scanning. The 3D plots obtained using this
      technique implicate cross-annihilation ECL reactions involving the complex itself
      and stable products resulting from its electrolysis. Combining this information
      with knowledge of the energetic requirements of the various reactions involved,
      suggests a mechanism involving traces of two emissive products, related to the
      loss of a methyl group from the triazole moiety. These products, while barely
      detectable electrochemically, are sufficiently emissive to influence and even
      dominate the ECL emission under some conditions.

PMID- 28451133
TI  - N-heterocyclic carbene induced reductive coupling of phosphorus tribromide.
      Isolation of a bromine bridged P-P bond and its subsequent reactivity.
AB  - The room temperature reaction of a 1 : 1 mixture of phosphorus tribromide (PBr3)
      and the N-heterocyclic carbene 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene
      (IPr) quantitatively affords the Lewis acid-base adduct (IPr)PBr3 (1).
      Interestingly, when 1 is heated between 55 and 65  degrees C for a period of
      several days, dark red crystals slowly begin to form in the reaction vessel
      accompanied by the release of bromine. The resulting crystalline sample,
      [P2(IPr)2Br3]Br ([2]Br), results from the reductive coupling of two equivalents
      of 1, and contains a cationic moiety with a P-P bond that is bridged by a bromine
      atom. Anion exchange reactions with Na[BArF4] (BArF4 = B(3,5-{CF3}2C6H3)4) afford
      [2][BArF4]. Abstraction of two equivalents of bromine allows for the isolation of
      the unprecedented dicationic species [P2(IPr)2Br2]2+ (3) which was isolated and
      structurally authenticated as two different [BArF4]- salts. Reaction of 2 with
      mild reductants such as SnBr2 or tetrakis(dimethylamino)ethylene (TDAE) affords
      [P2(IPr)2Br]+ (4) and the known radical cation [P2(IPr)2]+ (5), respectively.
      These studies show that relatively weak P-Br bonds present in compounds 1-4 can
      be cleaved in a straightforward manner to afford low oxidation state compounds in
      high yields.

PMID- 28451134
TI  - Intrinsic high water/ion selectivity of graphene oxide lamellar membranes in
      concentration gradient-driven diffusion.
AB  - Although graphene oxide lamellar membranes (GOLMs) are effective in blocking
      large organic molecules and nanoparticles for nanofiltration and ultrafiltration,
      water desalination with GOLM is challenging, with seriously controversial
      results. Here, a combined experimental and molecular dynamics simulation study
      shows that intrinsic high water/ion selectivity of GOLM was achieved in
      concentration gradient-driven diffusion, showing great promise in water
      desalination. However, in pressure-driven filtration the salt rejection was poor.
      This study unveils a long-overlooked reason behind the controversy in water
      desalination with GOLM and further provides a fundamental understanding on the in
      depth mechanism concerning the strong correlation of water/ion selectivity with
      the applied pressure and GO nanochannel length. Our calculations and experiments
      show that the applied pressure weakened the water-ion interactions in GO
      nanochannels and reduced their permeation selectivity, while the length of
      nanochannels dominated the mass transport processes and the ion selectivity. The
      new insights presented here may open up new opportunities for the optimization of
      GOLMs in this challenging area.

PMID- 28451135
TI  - Resolving the alpha-glycosidic linkage of arginine-rhamnosylated translation
      elongation factor P triggers generation of the first ArgRha specific antibody.
AB  - A previously discovered posttranslational modification strategy - arginine
      rhamnosylation - is essential for elongation factor P (EF-P) dependent rescue of
      polyproline stalled ribosomes in clinically relevant species such as Pseudomonas
      aeruginosa and Neisseria meningitidis. However, almost nothing is known about
      this new type of N-linked glycosylation. In the present study we used NMR
      spectroscopy to show for the first time that the alpha anomer of rhamnose is
      attached to Arg32 of EF-P, demonstrating that the corresponding
      glycosyltransferase EarP inverts the sugar of its cognate substrate dTDP-beta-l
      rhamnose. Based on this finding we describe the synthesis of an alpha
      rhamnosylated arginine containing peptide antigen in order to raise the first
      anti-rhamnosyl arginine specific antibody (anti-ArgRha). Using ELISA and Western
      Blot analyses we demonstrated both its high affinity and specificity without any
      cross-reactivity to other N-glycosylated proteins. Having the anti-ArgRha at hand
      we were able to visualize endogenously produced rhamnosylated EF-P. Thus, we
      expect the antibody to be not only important to monitor EF-P rhamnosylation in
      diverse bacteria but also to identify further rhamnosyl arginine containing
      proteins. As EF-P rhamnosylation is essential for pathogenicity, our antibody
      might also be a powerful tool in drug discovery.

PMID- 28451136
TI  - Converting disulfide bridges in native peptides to stable methylene thioacetals.
AB  - Disulfide bridges play a crucial role in defining and rigidifying the three
      dimensional structure of peptides. However, disulfides are inherently unstable in
      reducing environments. Consequently, the development of strategies aiming to
      circumvent these deficiencies - ideally with little structural disturbance - are
      highly sought after. Herein, we report a simple protocol converting the disulfide
      bond of peptides into highly stable methylene thioacetal. The transformation
      occurs under mild, biocompatible conditions, enabling the conversion of
      unprotected native peptides into analogues with enhanced stability. The developed
      protocol is applicable to a range of peptides and selective in the presence of a
      multitude of potentially reactive functional groups. The thioacetal modification
      annihilates the reductive lability and increases the serum, pH and temperature
      stability of the important peptide hormone oxytocin. Moreover, it is shown that
      the biological activities for oxytocin are retained.

PMID- 28451138
TI  - Competition between drum and quasi-planar structures in RhB18-: motifs for
      metallo-boronanotubes and metallo-borophenes.
AB  - Metal-doped boron clusters provide new opportunities to design nanoclusters with
      interesting structures and bonding. A cobalt-doped boron cluster, CoB18-, has
      been observed recently to be planar and can be viewed as a motif for metallo
      borophenes, whereas the D9d drum isomer as a motif for metallo-boronanotubes is
      found to be much higher in energy. Hence, whether larger doped boron drums are
      possible is still an open question. Here we report that for RhB18- the drum and
      quasi-planar structures become much closer in energy and co-exist experimentally,
      revealing a competition between the metallo-boronanotube and metallo-borophene
      structures. Photoelectron spectroscopy of RhB18- shows a complicated spectral
      pattern, suggesting the presence of two isomers. Quantum chemistry studies
      indicate that the D9d drum isomer and a quasi-planar isomer (Cs) compete for the
      global minimum. The enhanced stability of the drum isomer in RhB18- is due to the
      less contracted Rh 4d orbitals, which can have favorable interactions with the
      B18 drum motif. Chemical bonding analyses show that the quasi-planar isomer of
      RhB18- is aromatic with 10 pi electrons, whereas the observed RhB18- drum cluster
      sets a new record for coordination number of eighteen among metal complexes. The
      current finding shows that the size of the boron drum can be tuned by appropriate
      metal dopants, suggesting that even larger boron drums with 5d, 6d transition
      metal, lanthanide or actinide metal atoms are possible.

PMID- 28451137
TI  - Emissive nanoparticles from pyridinium-substituted tetraphenylethylene salts:
      imaging and selective cytotoxicity towards cancer cells in vitro and in vivo by
      varying counter anions.
AB  - Chemotherapeutics specifically targeting cancer cells without damaging healthy
      cells is the long-awaited goal of cancer treatment. In this paper, a series of
      nanoparticles (NanoTPES 1-4) assembled from pyridinium-substituted
      tetraphenylethylene salts were synthesized and investigated both in vitro and in
      vivo for this purpose. By changing the counter anions, NanoTPES 1-4 exhibit
      tunable emission colors, sizes and surface charges. NanoTPES 2 and 3 with
      tetraphenyl borate and tetra(4-chlorophenyl) borate as the respective anions
      selectively imaged and targeted mitochondria in cancer cells. Accordingly, these
      two nanoparticles specifically kill cancer cells with minimal effect on normal
      cells. Such selective cytotoxicity was attributed to the change of membrane
      potential and inhibition of ATP synthesis in the mitochondria of cancer cells.
      Furthermore, both NanoTPES 2 and 3 exhibited efficient tumor accumulation and
      tumor growth inhibition in vivo, with negligible systemic toxicity.

PMID- 28451139
TI  - The impact of grafted surface defects and their controlled removal on
      supramolecular self-assembly.
AB  - We demonstrate the use of covalently modified graphite as a convenient and
      powerful test-bed for the versatile investigation and control of 2-D
      crystallization at the liquid solid interface. Grafted aryls act as surface
      defects and create barriers to supramolecular self-assembly. An easily tunable
      grafting density allows for varying the effect of such defects on supramolecular
      self-assembly. Finally, the defects can be locally removed, triggering monolayer
      reconstructions and allowing in situ investigations of thermodynamically unstable
      or metastable morphologies.

PMID- 28451140
TI  - A genetically encoded multifunctional unnatural amino acid for versatile protein
      manipulations in living cells.
AB  - The genetic code expansion strategy allowed incorporation of unnatural amino
      acids (UAAs) bearing diverse functional groups into proteins, providing a
      powerful toolkit for protein manipulation in living cells. We report a
      multifunctional UAA, Nepsilon-p-azidobenzyloxycarbonyl lysine (PABK), that
      possesses a panel of unique properties capable of fulfilling various protein
      manipulation purposes. In addition to being used as a bioorthogonal ligation
      handle, an infrared probe and a photo-affinity reagent, PABK was shown to be
      chemically decaged by trans-cyclooctenols via a strain-promoted 1,3-dipolar
      cycloaddition, which provides a new bioorthogonal cleavage strategy for
      intracellular protein activation. The biocompatibility and efficiency of this
      method were demonstrated by decaging of a PABK-caged firefly luciferase under
      living conditions. We further extended this method to chemically rescue a
      bacterial toxin OspF inside mammalian host cells.

PMID- 28451141
TI  - Directly probing spin dynamics in a molecular magnet with femtosecond time
      resolution.
AB  - We show that a vanadium-chromium Prussian blue analogue, which is a room
      temperature molecule-based magnet, displays a fast magnetic response on a
      femtosecond timescale that is attributed to the super-exchange interaction
      between the metal ions. These dynamics are obtained from femtosecond Faraday
      magneto-optical (MO) measurements, performed at 50 and 300 K. Exciting at the
      ligand-to-metal charge-transfer (LMCT) band results in the formation of the 2E
      excited state on the Cr ion via intersystem crossing (ISC) from the 4LMCT state
      in less than 250 fs. Subsequent vibrational relaxation in the 2E state occurs on
      a 0.78 +/- 0.05 ps timescale at 50 K and 1.1 +/- 0.1 ps at 300 K. The MO
      measurements can detect the formation of the 2E state on the Cr ion from the
      change in the super-exchange interaction taking place as a result of the
      corresponding spin flip associated with the formation of the 2E state. These
      results open up a new avenue to study molecular magnets using a powerful method
      that is capable of directly probing spin dynamics on a sub-picosecond timescale
      in thin film environments.

PMID- 28451142
TI  - Ru-protein-Co biohybrids designed for solar hydrogen production: understanding
      electron transfer pathways related to photocatalytic function.
AB  - A series of Ru-protein-Co biohybrids have been prepared using the electron
      transfer proteins ferredoxin (Fd) and flavodoxin (Fld) as scaffolds for
      photocatalytic hydrogen production. The light-generated charge separation within
      these hybrids has been monitored by transient optical and electron paramagnetic
      resonance spectroscopies. Two distinct electron transfer pathways are observed.
      The Ru-Fd-Co biohybrid produces up to 650 turnovers of H2 utilizing an oxidative
      quenching mechanism for Ru(ii)* and a sequential electron transfer pathway via
      the native [2Fe-2S] cluster to generate a Ru(iii)-Fd-Co(i) charge separated state
      that lasts for ~6 ms. In contrast, a direct electron transfer pathway occurs for
      the Ru-ApoFld-Co biohybrid, which lacks an internal electron relay, generating
      Ru(i)-ApoFld-Co(i) charge separated state that persists for ~800 MUs and produces
      85 turnovers of H2 by a reductive quenching mechanism for Ru(ii)*. This work
      demonstrates the utility of protein architectures for linking donor and catalytic
      function via direct or sequential electron transfer pathways to enable stabilized
      charge separation which facilitates photocatalysis for solar fuel production.

PMID- 28451143
TI  - Understanding and predicting the potency of ROS-based enzyme inhibitors,
      exemplified by naphthoquinones and ubiquitin specific protease-2.
AB  - Recent studies have suggested that selective targeting of overexpressed enzymes
      in cancer cells by small molecules that induce the formation of reactive oxygen
      species (ROS) could be a viable approach in cancer therapy. One such example is
      the inactivation of ubiquitin specific protease-2 (USP2)-an emerging drug target
      to combat prostate cancer-by beta-lapachone, which has been identified to involve
      oxidation of the catalytic cysteine's thiol residue to sulfinic acid. A rational
      design of beta-lapachone analogs with improved activity requires a much better
      understanding of the variables that determine ROS production by this class of
      molecules. This crucial aspect was addressed via modulation of its 1,2
      naphthoquinone scaffold and establishment of a structure/activity relationship,
      regarding its ability to reduce molecular oxygen to a ROS. The same series of
      compounds was also examined in terms of their inhibitory effect on the enzymatic
      activity of USP2. One deduction from these investigations was that the ortho
      quinone motif in beta-lapachone is much better suited for the catalytic reduction
      of oxygen than the para-quinone motif and some approved quinone based drugs. A
      broader conclusion, obtained from the series of compounds with ortho-quinone
      motifs, is that only the agents whose redox potential is in the narrow range of 
      0.3 +/- 0.1 V (vs. Ag/AgCl in pH 7.5 aqueous buffer) induce the formation of ROS.
      The excellent correlation between the ROS production ability and the USP2
      inhibition potency emphasizes that the relatively easy, fast, and reliable
      testing of electrocatalytic oxygen reduction by small molecules might be applied
      to screening and evaluating new drug candidates for similar targets.

PMID- 28451144
TI  - Photochemical pump and NMR probe to monitor the formation and kinetics of
      hyperpolarized metal dihydrides.
AB  - On reaction of IrI(CO)(PPh3)21 with para-hydrogen (p-H2), Ir(H)2I(CO)(PPh3)22 is
      formed which exhibits strongly enhanced 1H NMR signals for its hydride
      resonances. Complex 2 also shows similar enhancement of its NMR spectra when it
      is irradiated under p-H2. We report the use of this photochemical reactivity to
      measure the kinetics of H2 addition by laser-synchronized reactions in
      conjunction with NMR. The single laser pulse promotes the reductive elimination
      of H2 from Ir(H)2I(CO)(PPh3)22 in C6D6 solution to form the 16-electron precursor
      1, back reaction with p-H2 then reforms 2 in a well-defined nuclear spin-state.
      The build up of this product can be followed by incrementing a precisely
      controlled delay (tau), in millisecond steps, between the laser and the NMR
      pulse. The resulting signal vs. time profile shows a dependence on p-H2 pressure.
      The plot of kobs against p-H2 pressure is linear and yields the second order rate
      constant, k2, for H2 addition to 1 of (3.26 +/- 0.42) * 102 M-1 s-1. Validation
      was achieved by transient-UV-vis absorption spectroscopy which gives k2 of (3.06
      +/- 0.40) * 102 M-1 s-1. Furthermore, irradiation of a C6D6 solution of 2 with
      multiple laser shots, in conjunction with p-H2 derived hyperpolarization, allows
      the detection and characterisation of two minor reaction products, 2a and 3,
      which are produced in such low yields that they are not detected without
      hyperpolarization. Complex 2a is a configurational isomer of 2, while 3 is formed
      by substitution of CO by PPh3.

PMID- 28451146
TI  - A Giving Pledge of sharing discovery.
AB  - Editor-in-Chief Dan Nocera encourages the chemical science community to share the
      wealth of their most exceptional scientific discoveries, so that this is freely
      available to all.

PMID- 28451145
TI  - Competitive method-based electrochemiluminescent assay with protein-nucleotide
      conversion for ratio detection to efficiently monitor the drug resistance of
      cancer cells.
AB  - A simple and highly-efficient approach to monitor the expression of P
      glycoprotein (P-gp) in cells was urgently needed to demonstrate the drug
      resistance of cancer cells. Herein, a competitive method-based
      electrochemiluminescent (ECL) assay with a single ECL indicator was proposed for
      the first time to efficiently estimate the concentration ratio of two proteins.
      By converting the different proteins to partially coincident nucleotide sequences
      via a sandwich type immunoassay on magnetic beads, the concentration ratio
      related ECL signals could be obtained via competitive nucleotide hybridization on
      an electrode surface. This method could thoroughly overcome the limitations of
      simultaneous ECL assays via multiple ECL indicators with inevitable cross
      reactions. At the same time, rolling circle amplification was employed to improve
      the detection performances, especially the detection limit and sensitivity. With
      P-gp and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a model, the
      proposed ECL assay was successfully employed to monitor the drug resistance of
      cancer cells. Compared with conventional technologies, improved sensitivity and
      accuracy were achieved with a correlation coefficient of 0.9928 and a detection
      limit of 0.52%. Success in the establishment of the competitive method-based ECL
      assay offered an efficient strategy to demonstrate the concentration ratio of two
      proteins and a potential approach for detecting other proteins and nucleotide
      sequences, revealing a new avenue for ultrasensitive biomolecule diagnostics,
      especially in cell function research.

PMID- 28451147
TI  - In situ tether formation from amines and alcohols enabling highly selective Tsuji
      Trost allylation and olefin functionalization.
AB  - The use of tethers allows to overcome reactivity and selectivity issues often
      encountered with intermolecular reactions. Although tethers have been
      successfully applied for decades, their installation and removal usually requires
      additional steps. This minireview highlights the recent development of tethers
      that can be installed in situ on (homo)-allyl amines or alcohols for Tsuji-Trost
      allylation or double bond functionalization. In particular, the use of (hemi
      )acetal tethers for highly regioselective and enantioselective Tsuji-Trost
      allylation was recently reported. Hydroamination of olefins starting from allylic
      amines could be achieved via a retro Cope-elimination using catalytic amount of
      an aldehyde for tether formation. Finally, bifunctionalizations of olefins were
      developed using either carbon dioxide or carbonyls/imines as tether precursors.
      These recent breakthroughs greatly enhanced the efficiency of the tethering
      approach for olefin functionalization, and will make it even more attractive for
      synthetic chemists in the future.

PMID- 28451150
TI  - Pharmaceutical polymorph control in a drug-mimetic supramolecular gel.
AB  - We report the synthesis of a bis(urea) gelator designed to specifically mimic the
      chemical structure of the highly polymorphic drug substance ROY. Crystallization
      of ROY from toluene gels of this gelator results in the formation of the
      metastable red form instead of the thermodynamic yellow polymorph. In contrast,
      all other gels and solution control experiments give the yellow form.
      Conformational and crystal structure prediction methods have been used to propose
      the structure of the gel and show that the templation of the red form by the
      targeted gel results from conformational matching of the gelator to the ROY
      substrate coupled with overgrowth of ROY onto the local periodic structure of the
      gel fibres.

PMID- 28451148
TI  - Site-selective Suzuki-Miyaura coupling of heteroaryl halides - understanding the
      trends for pharmaceutically important classes.
AB  - Suzuki-Miyaura cross-coupling reactions of heteroaryl polyhalides with aryl
      boronates are surveyed. Drawing on data from literature sources as well as
      bespoke searches of Pfizer's global chemistry RKB and CAS Scifinder(r) databases,
      the factors that determine the site-selectivity of these reactions are discussed
      with a view to rationalising the trends found.

PMID- 28451149
TI  - Antibody fragments as nanoparticle targeting ligands: a step in the right
      direction.
AB  - Recent advances in nanomedicine have shown that dramatic improvements in
      nanoparticle therapeutics and diagnostics can be achieved through the use of
      disease specific targeting ligands. Although immunoglobulins have successfully
      been employed for the generation of actively targeted nanoparticles, their use is
      often hampered by the suboptimal characteristics of the resulting complexes.
      Emerging data suggest that a switch in focus from full antibodies to antibody
      derived fragments could help to alleviate these problems and expand the potential
      of antibody-nanoparticle conjugates as biomedical tools. This review aims to
      highlight how antibody derived fragments have been utilised to overcome both
      fundamental and practical issues encountered during the design and application of
      antibody-targeted nanoparticles.

PMID- 28451151
TI  - Pyramidalization/twisting of the amide functional group via remote steric
      congestion triggered by metal coordination.
AB  - For decades, the planarity of the amide functional group has garnered sustained
      interest in organic chemistry, enticing chemists to deform its usually
      characteristic high-fidelity plane. As opposed to the construction of amides that
      are distorted by imposing rigid covalent bond assemblies, we demonstrate herein
      the deformation of the amide plane through increased steric bulk in the periphery
      of the amide moiety, which is induced by coordination to metal cations. A
      crystallographic analysis revealed that the thus obtained amides exhibit
      significant pyramidalization and twisting upon coordination to the metals, while
      the amide functional group remained intact. The observed deformation, which
      should be attributed to through-space interactions, substantially enhanced the
      solvolytic cleavage of the amide, providing compelling evidence that temporary
      crowding in the periphery of the amide functional group may be used to control
      the reactivity of amides.

PMID- 28451152
TI  - Gradient doping of phosphorus in Fe2O3 nanoarray photoanodes for enhanced charge
      separation.
AB  - Hematite (alpha-Fe2O3) is a promising candidate for solar-to-hydrogen energy
      conversion. However, the low carrier mobility and extremely high charge
      recombination rate limit the practical application of hematite in solar water
      splitting. This paper describes the fabrication of a Fe2O3 photoanode with
      gradient incorporation of phosphorus (P) employing a facile dipping and annealing
      method to improve the charge separation for enhanced photoelectrochemical water
      oxidation. This gradient P incorporation increases the width of band bending over
      a large region in Fe2O3, which is crucial for promoting the charge separation
      efficiency in the bulk. Although both gradient and homogeneous P-incorporated
      Fe2O3 samples exhibit similar electrical conductivity, the Fe2O3 electrode with a
      gradient P concentration presents an additional charge separation effect. A
      photocurrent of ~1.48 mA cm-2 is obtained at 1.23 V vs. reversible hydrogen
      electrode (vs. RHE) under air mass 1.5G illumination. Additionally, the H2O
      oxidation kinetics of Fe2O3 with gradient P incorporation was further improved
      upon loading cobalt phosphate as cocatalyst, reaching a photocurrent of ~2.0 mA
      cm-2 at 1.23 V vs. RHE.

PMID- 28451153
TI  - Selective synthesis of unsymmetric dibenzo[a,e]pentalenes by a rhodium-catalysed
      stitching reaction.
AB  - A rhodium-catalysed stitching reaction between 2-(silylethynyl)arylboronates and
      2-(silylethynyl)aryl bromides has been developed for the synthesis of unsymmetric
      dibenzo[a,e]pentalenes. The introduction of appropriately sized silyl groups on
      the starting substrates led to a high crossover selectivity without using an
      excess amount of either substrate. The present stitching reaction could produce a
      variety of unsymmetric dibenzo[a,e]pentalene derivatives, including those with
      electronically different substituents on the fused benzene rings as well as
      heteroarene fused compounds. Desilylative halogenation was also demonstrated to
      synthesise the corresponding halogenated dibenzo[a,e]pentalenes, which can be
      used as building blocks for further chemical transformations.

PMID- 28451154
TI  - Inner-sphere vs. outer-sphere reduction of uranyl supported by a redox-active,
      donor-expanded dipyrrin.
AB  - The uranyl(vi) complex UO2Cl(L) of the redox-active, acyclic diimino-dipyrrin
      anion, L- is reported and its reaction with inner- and outer-sphere reductants
      studied. Voltammetric, EPR-spectroscopic and X-ray crystallographic studies show
      that chemical reduction by the outer-sphere reagent CoCp2 initially reduces the
      ligand to a dipyrrin radical, and imply that a second equivalent of CoCp2 reduces
      the U(vi) centre to form U(v). Cyclic voltammetry indicates that further outer
      sphere reduction to form the putative U(iv) trianion only occurs at strongly
      cathodic potentials. The initial reduction of the dipyrrin ligand is supported by
      emission spectra, X-ray crystallography, and DFT; the latter also shows that
      these outer-sphere reactions are exergonic and proceed through sequential, one
      electron steps. Reduction by the inner-sphere reductant [TiCp2Cl]2 is also likely
      to result in ligand reduction in the first instance but, in contrast to the outer
      sphere case, reduction of the uranium centre becomes much more favoured, allowing
      the formation of a crystallographically characterised, doubly-titanated U(iv)
      complex. In the case of inner-sphere reduction only, ligand-to-metal electron
      transfer is thermodynamically driven by coordination of Lewis-acidic Ti(iv) to
      the uranyl oxo, and is energetically preferable over the disproportionation of
      U(v). Overall, the involvement of the redox-active dipyrrin ligand in the
      reduction chemistry of UO2Cl(L) is inherent to both inner- and outer-sphere
      reduction mechanisms, providing a new route to accessing a variety of U(vi),
      U(v), and U(iv) complexes.

PMID- 28451155
TI  - Serine promoted synthesis of peptide thioester-precursor on solid support for
      native chemical ligation.
AB  - Fmoc solid phase peptide synthesis of thioesters for the chemical synthesis of
      proteins via native chemical ligation is a challenge. We have developed a
      versatile approach for direct synthesis of peptide thioesters from a solid
      support utilizing Fmoc chemistry. Peptide thioester synthesis is performed by the
      formation of a cyclic urethane moiety via a selective reaction of the backbone
      amide chain with the side group of serine. The activated cyclic urethane moiety
      undergoes displacement by a thiol to generate the thioester directly from the
      solid support. Importantly, the method activates the serine residue for the
      synthesis of peptide thioesters; thus it is fully automated and free of the types
      of resins, linkers, handles, and unnatural amino acids typically needed for the
      synthesis of peptide thioesters using Fmoc chemistry. The resulting thioester is
      free of epimerization and is successfully applied for the synthesis of longer
      peptides using NCL.

PMID- 28451156
TI  - How covalence breaks adsorption-energy scaling relations and solvation restores
      them.
AB  - It is known that breaking the scaling relations between the adsorption energies
      of *O, *OH, and *OOH is paramount in catalyzing more efficiently the reduction of
      O2 in fuel cells and its evolution in electrolyzers. Taking metalloporphyrins as
      a case study, we evaluate here the adsorption energies of those adsorbates on the
      metal centers Cr, Mn, Fe, Co, Ni and Cu, using H, F, OH, NH2, CH3, and BH2 as
      ring ligands. We show that covalence systematically breaks scaling relations
      under vacuum by strengthening certain M-OOH bonds. However, covalence modifies
      adsorbate solvation in solution depending on the degree of covalence of the metal
      adsorbate bonds. The two effects have similar magnitudes and opposite signs, such
      that scaling relations are restored in solution. Thus, solvation is a crucial
      ingredient that must be taken into account in studies aimed at breaking scaling
      relations in solution. Our findings suggest that the choice of metal and ligand
      determines the catalytic activity within the limits imposed by scaling relations,
      whereas the choice of an appropriate solvent can drive such activity beyond those
      limits.

PMID- 28451157
TI  - A cooperative-binding split aptamer assay for rapid, specific and ultra-sensitive
      fluorescence detection of cocaine in saliva.
AB  - Sensors employing split aptamers that reassemble in the presence of a target can
      achieve excellent specificity, but the accompanying reduction of target affinity
      mitigates any overall gains in sensitivity. We for the first time have developed
      a split aptamer that achieves enhanced target-binding affinity through
      cooperative binding. We have generated a split cocaine-binding aptamer that
      incorporates two binding domains, such that target binding at one domain greatly
      increases the affinity of the second domain. We experimentally demonstrate that
      the resulting cooperative-binding split aptamer (CBSA) exhibits higher target
      binding affinity and is far more responsive in terms of target-induced aptamer
      assembly compared to the single-domain parent split aptamer (PSA) from which it
      was derived. We further confirm that the target-binding affinity of our CBSA can
      be affected by the cooperativity of its binding domains and the intrinsic
      affinity of its PSA. To the best of our knowledge, CBSA-5335 has the highest
      cocaine affinity of any split aptamer described to date. The CBSA-based assay
      also demonstrates excellent performance in target detection in complex samples.
      Using this CBSA, we achieved specific, ultra-sensitive, one-step fluorescence
      detection of cocaine within fifteen minutes at concentrations as low as 50 nM in
      10% saliva without signal amplification. This limit of detection meets the
      standards recommended by the European Union's Driving under the Influence of
      Drugs, Alcohol and Medicines program. Our assay also demonstrates excellent
      reproducibility of results, confirming that this CBSA-platform represents a
      robust and sensitive means for cocaine detection in actual clinical samples.

PMID- 28451158
TI  - Probe for simultaneous membrane and nucleus labeling in living cells and in vivo
      bioimaging using a two-photon absorption water-soluble Zn(ii) terpyridine complex
      with a reduced pi-conjugation system.
AB  - Small, biocompatible and water-soluble molecules with high two-photon absorption
      (2PA) cross-section values (delta) are in high demand for specific bioimaging
      applications. Here, two novel terpyridine derivative ligands with donor-acceptor
      (D-A) (L1) and donor-pi-acceptor (D-pi-A) (L2) models, and their corresponding
      Zn(ii) complexes are designed and characterized. It was found that the two-photon
      absorption cross section values (delta) in the near-infrared region (NIR, about
      800 nm) are significantly enhanced for complexes 1 and 2 compared to their free D
      A type ligand L1, while those of complexes 3 and 4 were greatly decreased
      relative to their free ligand L2, thus confirming that the smaller ligand (D-A
      type) displays a suitable Turn-ON fluorescence pair for two-photon fluorescence
      microscopy (2PFM). Firstly, the potential of simultaneously labeling a live cell
      plasma membrane and nucleus using complex 1 is demonstrated. In addition, live
      larval and adult zebrafish incubated with an optimal concentration of 1
      demonstrated clear brain uptake. Lastly and importantly, using such a probe to
      visualize the blood-brain-barrier (BBB) capillary endothelial cells and penetrate
      the BBB into the central nervous system (CNS) intravenously in a mouse model is
      also explored.

PMID- 28451159
TI  - Dual-emissive nanoarchitecture of lanthanide-complex-modified silica particles
      for in vivo ratiometric time-gated luminescence imaging of hypochlorous acid.
AB  - We have developed a ratiometric time-gated luminescence sensory system for in
      vivo imaging of hypochlorous acid (HClO) by preparing a dual-emissive
      nanoarchitecture of europium- and terbium-complex-modified silica nanoparticles.
      The design of this nanoarchitecture is based on our new finding that the strong,
      long-lived luminescence of the beta-diketonate-Eu3+ complex can be rapidly and
      selectively quenched by HClO. Therefore, the beta-diketonate-Eu3+ complex was
      decorated on the surface of the silica nanoparticles for responding to HClO,
      while a HClO-insensitive luminescent terbium complex was immobilized in the inner
      solid core of the nanoparticles to serve as an internal standard. This
      nanosensing probe combines the advantages of both ratiometric and time-gated
      detection modes to afford high accuracy and sensitivity. Upon exposure to HClO,
      the nanoprobe displayed a remarkable luminescence color change from red to green,
      and the intensity ratio of the green over the red luminescence (I539/I607) showed
      a rapid, sensitive and selective response to HClO. Additionally, the feasibility
      of using the nanoprobe for intracellular detection of exogenous and endogenous
      HClO and for real-time mapping of HClO in small laboratory animals has been
      demonstrated via ratiometric time-gated luminescence imaging microscopy. The
      results reveal that the constructed nanoarchitecture cloud is a favorable and
      useful sensing probe for the real-time imaging of HClO in vivo with high
      specificity and contrast.

PMID- 28451160
TI  - Greigite Fe3S4 as a new anode material for high-performance sodium-ion batteries.
AB  - Transition metal dichalcogenide materials have been considered as promising anode
      materials for rechargeable sodium-ion batteries because of their high specific
      capacity and low cost. Here, we demonstrate an iron sulfide Fe3S4 as a new anode
      material for a rechargeable sodium-ion battery. The involved conversion mechanism
      has been proved when the as-prepared Fe3S4 was used as the host material for
      sodium storage. Remarkably, a compound FeS x with quantum size generated by
      conversion reaction overcame the kinetic and thermodynamic constraints of
      chemical conversion to achieve superior cycling and rate capability. As a result,
      the as-prepared Fe3S4 electrode delivers a high reversible specific capacity of
      548 mA h g-1 at 0.2 A g-1, together with an excellent cycling stability of 275 mA
      h g-1 after 3500 cycles at 20 A g-1.

PMID- 28451161
TI  - Copper-catalyzed dehydrogenative borylation of terminal alkynes with
      pinacolborane.
AB  - LCuOTf complexes [L = cyclic (alkyl)(amino)carbenes (CAACs) or N-heterocyclic
      carbenes (NHCs)] selectively promote the dehydrogenative borylation of C(sp)-H
      bonds at room temperature. It is shown that sigma,pi-bis(copper) acetylide and
      copper hydride complexes are the key catalytic species.

PMID- 28451162
TI  - Unified synthesis of mono/bis-arylated phenols via RhIII-catalyzed
      dehydrogenative coupling.
AB  - 2,6-Bis-arylated phenols are rarely reported and are synthetically challenging.
      Directed C-H functionalization reactions, using a directing group (DG), might
      provide a convenient solution to their synthesis. However, this strategy usually
      results in partial cleavage of the directing group, preventing further/second C-H
      activation cascades. Herein we report a general strategy that allows for the
      precise control of the oxidation pathways so that directing groups can be either
      preserved or cleaved. We found that N-phenoxyacetamides could undergo ortho
      arylation reactions with or without an external oxidant, yielding products with
      different oxidation states, notably the rare bis-arylated phenols. Notably, a
      unique rhodacycle intermediate was isolated, characterized by X-ray
      crystallography, and confirmed to be an active catalyst. Switching between
      internal and external oxidation could be a general strategy in diverse directed C
      H functionalization reactions to realize bis-functionalized products.

PMID- 28451163
TI  - Evaluation of intracellular telomerase activity through cascade DNA logic gates.
AB  - Telomerase plays a vital role in cancer and aging, and telomerase activity
      detection has drawn great attention recently. However, a feasible in situ imaging
      system for intracellular telomerase is still a challenge. Here, we develop a
      novel approach to image intracellular telomerase activity using DNA-based
      computation. A cascade nucleic acid logic gate that responded to intracellular
      telomerase was constructed. A telomerase substrate (TS) probe, extended by
      intracellular telomerase, worked as an input to initiate computation cascades. In
      this way, intracellular telomerase could be clearly indicated by fluorophore
      labeled nucleic acids as the output. Through one-step incubation, evaluation of
      the intracellular telomerase activity for a HeLa cell line and the ability to
      differentiate cancer cells from normal cells could be realized. Furthermore, the
      response of intracellular telomerase activity to a telomerase-inhibiting model
      drug was observed using the proposed method. Thus, this intracellular telomerase
      computation device will allow improvements in studying the relationship between
      telomerase and cancer, and may help to develop telomerase inhibitors. This
      finding also expands the applications of DNA computational techniques in cells.

PMID- 28451164
TI  - Regioisomer effects of [70]fullerene mono-adduct acceptors in bulk heterojunction
      polymer solar cells.
AB  - Despite numerous organic semiconductors being developed during the past decade,
      C70 derivatives are predominantly used as electron acceptors in efficient polymer
      solar cells (PSCs). However, as-prepared C70 mono-adducts intrinsically comprise
      regioisomers that would mask individual device performances depending on the
      substituent position on C70. Herein, we separate the regioisomers of C70 mono
      adducts for PSC applications for the first time. Systematic investigations of the
      substituent position effect using a novel symmetric C70 mono-adduct ([70]NCMA)
      and a prevalent, high-performance one ([70]PCBM) reveals that we can control the
      structures of the blend films with conjugated polymers and thereby improve the
      PSC performances by regioisomer separation. Our approach demonstrates the
      significance of exploring the best-matching regioisomer of C70 mono-adducts with
      high-performance conjugated polymers, which would achieve a remarkable progress
      in PSC devices.

PMID- 28451165
TI  - Highly planar diarylamine-fused porphyrins and their remarkably stable radical
      cations.
AB  - Oxidative fusion reactions of meso-phenoxazino Ni(ii) porphyrin were found to be
      temperature dependent, giving rise to either a doubly phenylene-fused product at
      room temperature or a singly phenoxazine-fused product at 70  degrees C. The
      latter was further oxidized to a doubly phenoxazine-fused Ni(ii) porphyrin, which
      was subsequently converted to the corresponding free base porphyrin and Zn(ii)
      porphyrin. Compared to previously reported diphenylamine-fused porphyrins that
      displayed a molecular twist, doubly phenoxazine-fused porphyrins exhibited
      distinctly different properties owing to their highly planar structures, such as
      larger fluorescence quantum yields, formation of an offset face-to-face dimer
      both in solution and the solid state, and the generation of a mixed-valence pi
      radical cation dimer upon electrochemical oxidation. One-electron oxidation of
      the phenoxazine-fused Ni(ii) porphyrin with Magic Blue gave the corresponding
      radical cation, which was certainly stable and could be isolated by separation
      over a silica gel column but slowly chlorinated at the reactive beta-positions in
      the solid state. This finding led to us to examine beta,beta'-dichlorinated
      phenoxazine-fused and diphenylamine-fused Ni(ii) porphyrins, which, upon
      treatment with Magic Blue, provided remarkably stable radical cations to an
      unprecedented level. It is actually possible to purify these radical cations by
      silica gel chromatography, and they can be stored for over 6 months without any
      sign of deterioration. Moreover, they exhibited no degradation even after the
      CH2Cl2 solution was washed with water. However, subtle structural differences
      (planar versus partly twisted) led to different crystal packing structures and
      solid-state magnetic properties.

PMID- 28451166
TI  - Selective detection of N6-methyladenine in DNA via metal ion-mediated replication
      and rolling circle amplification.
AB  - N6-methyladenine (6mA) is reported as a potential epigenetic marker in eukaryotic
      genomes. However, accurate identification of the location of 6mA in DNA remains a
      challenging task. Here, we show that Ag+ can selectively stabilize the A-C
      mismatch and efficiently promote primer extension. In contrast, the complex of
      6mA-Ag+-C is instable and therefore cannot be recognized by DNA polymerases,
      resulting in the termination of primer extension. Based on this finding, we
      successfully identified and quantified 6mA at the single-base level through the
      analysis of gel bands of extended primers and fluorescence measurements combined
      with rolling circle amplification. The high selectivity and sensitivity of this
      strategy may provide a new platform for the efficient analysis of 6mA in DNA in
      the future.

PMID- 28451167
TI  - Homochiral oligomers with highly flexible backbones form stable H-bonded
      duplexes.
AB  - Two homochiral building blocks featuring a protected thiol, an alkene and a H
      bond recognition unit (phenol or phosphine oxide) have been prepared. Iterative
      photochemical thiol-ene coupling reactions were used to synthesize oligomers
      containing 1-4 phosphine oxide and 1-4 phenol recognition sites. Length
      complementary H-bond donor and H-bond acceptor oligomers were found to form
      stable duplexes in toluene. NMR titrations and thermal denaturation experiments
      show that the association constant and the enthalpy of duplex formation increase
      significantly for every additional H-bonding unit added to the chain. There is an
      order of magnitude increase in stability for each additional H-bonding
      interaction at room temperature indicating that all of the H-bonding sites are
      fully bound to their complements in the duplexes. The backbone of the thiol-ene
      duplexes is a highly flexible alkane chain, but this conformational flexibility
      does not have a negative impact on binding affinity. The average effective
      molarity for the intramolecular H-bonding interactions that zip up the duplexes
      is 18 mM. This value is somewhat higher than the EM of 14 mM found for a related
      family of duplexes, which have the same recognition units but a more rigid
      backbone prepared using reductive amination chemistry. The flexible thiol-ene
      AAAA.DDDD duplex is an order of magnitude more stable than the rigid reductive
      amination AAAA.DDDD duplex. The backbone of the thiol-ene system retains much of
      its conformational flexibility in the duplex, and these results show that highly
      flexible molecules can make very stable complexes, provided there is no
      significant restriction of degrees of freedom on complexation.

PMID- 28451168
TI  - Mechanistic study of CBT-Cys click reaction and its application for identifying
      bioactive N-terminal cysteine peptides in amniotic fluid.
AB  - CBT-Cys click condensation reaction has a high second-order reaction rate
      constant and has found wide applicability in recent years. However, its reaction
      mechanism has not been experimentally validated and its application for
      identifying bioactive N-terminal Cys peptides in real clinical samples has not
      been reported. Herein, firstly, by employing induced nanoelectrospray ionization
      mass spectrometry (InESI-MS) and a home-built micro-reactor, we successfully
      intercepted and structurally characterized the crucial intermediate in this click
      reaction for the first time. With the intermediate, the proposed mechanism of
      this reaction was corroborated. Moreover, we also applied this MS setup to
      monitor the reaction in real time and obtained the second-order reaction rate
      constants of this reaction at different pH values. After mechanistic study, we
      applied this click reaction for identifying bioactive N-terminal cysteine
      peptides in amniotic fluid (AF). Eight unique N-terminal Cys peptides in AF,
      three of which are located in the functional domain regions of their
      corresponding proteins, were identified with a false positive rate less than 1%.
      One of the three peptides was found able to inhibit the growth of uterine
      endometrial cancer HEC-1-B cells but not the endometrial normal cells via a
      typical apoptotic pathway. With its mechanism satisfactorily elucidated, the
      kinetic parameters obtained, as well as its application for fishing bioactive N
      terminal Cys peptides from vast complex clinical samples, we anticipate that this
      CBT-Cys click reaction could be applied more widely for the facile isolation,
      site-specific identification, and quantification of N-terminal Cys-containing
      peptides in complex biological samples.

PMID- 28451169
TI  - Ultrafast transient IR spectroscopy and DFT calculations of ruthenium(ii)
      polypyridyl complexes.
AB  - Ultrafast time-resolved infrared spectroscopy of [Ru(bpy)3]2+ (bpy = 2,2'
      bipyridine), [Ru(mbpy)3]2+ (mbpy = 6-methyl-2,2'-bipyridine) and [Ru(mphen)3]2+
      (mphen = 2-methyl-1,10'-phenanthroline) in deuterated acetonitrile serves to
      elucidate the evolution of the system following pulsed excitation into the 1MLCT
      band at 400 nm. While for [Ru(bpy)3]2+ no intermediate state can be evidenced for
      the relaxation of the corresponding 3MLCT state back to the ground state, for
      [Ru(mbpy)3]2+ and [Ru(mphen)3]2+ an intermediate state with a lifetime of about
      400 ps is observed. The species associated IR difference spectra of this state
      are in good agreement with the calculated difference spectra of the lowest energy
      3dd state using DFT. The calculated potential energy curves for all the complexes
      in the triplet manifold along the metal-ligand distance show that for
      [Ru(bpy)3]2+ the 3dd state is at a higher energy than the 3MLCT state and that
      there is a substantial barrier between the two minima. For [Ru(mbpy)3]2+ and
      [Ru(mphen)3]2+, the 3dd state is at a lower energy than the 3MLCT state.

PMID- 28451170
TI  - Cycloheptatrienyl trianion: an elusive bridge in the search of exchange coupled
      dinuclear organolanthanide single-molecule magnets.
AB  - The preparation of eta-cyclopentadienyl (eta5-C5R5), eta-arene (eta6-C6R6), and
      eta-cyclooctatetraenyl (eta8-C8R8) bridging motifs are common in organometallic
      chemistry; however, the synthetic preparation of eta-cycloheptatrienyl (eta7
      C7R7) bridging motifs has remained a synthetic challenge in 4f chemistry. To this
      end, we have developed a synthetic route towards a series of rare dinuclear
      organolanthanide inverse sandwich complexes containing the elusive eta7-C7H7
      bridge. Herein, we present the structures and magnetic properties of the
      lanthanide inverse sandwich complexes [KLn2(C7H7)(N(SiMe3)2)4] (Ln = GdIII (1),
      DyIII (2), ErIII (3)) and [K(THF)2Er2(C7H7)(N(SiMe3)2)4] (4). These compounds are
      the first single-molecule magnets (SMMs) to feature this type of bridging motif.
      Furthermore, eta7-C7H7 was found to efficiently promote ferromagnetic exchange
      interactions between metal ions. Variable temperature dc magnetic susceptibility
      measurements and subsequent simulations give significant exchange constants of J
      = +1.384, +1.798, and +3.149 cm-1 and dipolar constants of J = -0.603, -0.601,
      and -0.475 cm-1 for compounds 2-4, respectively. Frequency dependent ac
      susceptibility measurements under an applied static field resulted in the
      observation of dual relaxation processes, and brought forth a greater
      understanding of the intermolecularly driven process at high frequency. In
      particular, this type of analysis of compound 3 under 800 Oe elicited an energy
      barrier of Ueff = 58 K. Ab initio calculations were performed in order to
      understand the nature of magnetic coupling and the origin of slow relaxation of
      magnetisation. Through these studies, the effect of the amido ancillary ligands
      on the magnetic axiality of the lanthanide ions was found to be competitive with
      the crystal field of the eta7-C7H7 pi-electron cloud. Our findings suggest that
      the tunability of the dipolar and exchange components of the magnetic
      interactions lie within the dihedral angle imposed by the amido ligands, thus
      offering potential for the development of new exchange coupled lanthanide
      systems.

PMID- 28451171
TI  - Antiangiogenic platinum through glycan targeting.
AB  - Heparan sulfate is identified as a ligand receptor for polynuclear platinum anti
      cancer agents through sulfate cluster binding. We present a new biological role
      for platinum and coordination compounds and a new target for metal-based drugs
      while presenting a new chemotype for heparanase and growth factor inhibition
      through modulation (metalloshielding) of their interactions. Masking of
      extracellular (ECM)-resident heparan sulfate (HS) through metalloshielding
      results in very effective inhibition of physiologically critical HS functions
      including enzyme (heparanase, HPSE) and protein growth factor recognition. The
      interaction of the highly cationic polynuclear platinum complexes (PPCs) with the
      highly sulfated pentasaccharide Fondaparinux (FPX, in this case as a model HS
      like substrate) results in inhibition of its cleavage by the HS-related enzyme
      heparanase. Binding of the fibroblast growth factor FGF-2 to HS is also inhibited
      with consequences for downstream signalling events as measured by a reduction in
      accumulation of phospho-S6 ribosomal protein in human colon tumor HCT-116 cells.
      The end-point of inhibition of HPSE activity and growth factor growth factor
      signaling is the prevention of cell invasion and angiogenesis. Finally these
      events culminate in inhibition of HCT-116 cell invasion at sub-cytotoxic
      concentrations and the process of angiogenesis. A competition assay shows that
      Fondaparinux can sequester the 8+ TriplatinNC from bound DNA, emphasising the
      strength of PPC-HS interactions. Altering the profile of platinum agents from
      cytotoxic to anti-metastatic has profound implications for future directions in
      the development of platinum-based chemotherapeutics.

PMID- 28451172
TI  - Metalloporphyrin-modified semiconductors for solar fuel production.
AB  - We report a direct one-step method to chemically graft metalloporphyrins to a
      visible-light-absorbing gallium phosphide semiconductor with the aim of
      constructing an integrated photocathode for light activating chemical
      transformations that include capturing, converting, and storing solar energy as
      fuels. Structural characterization of the hybrid assemblies is achieved using
      surface-sensitive spectroscopic methods, and functional performance for
      photoinduced hydrogen production is demonstrated via three-electrode
      electrochemical testing combined with photoproduct analysis using gas
      chromatography. Measurements of the total per geometric area porphyrin surface
      loadings using a cobalt-porphyrin based assembly indicate a turnover frequency
      >=3.9 H2 molecules per site per second, representing the highest reported to date
      for a molecular-catalyst-modified semiconductor photoelectrode operating at the
      H+/H2 equilibrium potential under 1-sun illumination.

PMID- 28451173
TI  - A novel route for preparing 5' cap mimics and capped RNAs: phosphate-modified cap
      analogues obtained via click chemistry.
AB  - The significant biological role of the mRNA 5' cap in translation initiation
      makes it an interesting subject for chemical modifications aimed at producing
      useful tools for the selective modulation of intercellular processes and
      development of novel therapeutic interventions. However, traditional approaches
      to the chemical synthesis of cap analogues are time-consuming and labour
      intensive, which impedes the development of novel compounds and their
      applications. Here, we explore a different approach for synthesizing 5' cap
      mimics, making use of click chemistry (CuAAC) to combine two mononucleotide units
      and yield a novel class of dinucleotide cap analogues containing a triazole ring
      within the oligophosphate chain. As a result, we synthesized a library of 36 mRNA
      cap analogues differing in the location of the triazole ring, the polyphosphate
      chain length, and the type of linkers joining the phosphate and the triazole
      moieties. After biochemical evaluation, we identified two analogues that, when
      incorporated into mRNA, produced transcripts translated with efficiency similar
      to compounds unmodified in the oligophosphate bridge obtained by traditional
      synthesis. Moreover, we demonstrated that the triazole-modified cap structures
      can be generated at the RNA 5' end using two alternative capping strategies:
      either the typical co-transcriptional approach, or a new post-transcriptional
      approach based on CuAAC. Our findings open new possibilities for developing
      chemically modified mRNAs for research and therapeutic applications, including
      RNA-based vaccinations.

PMID- 28451174
TI  - Reactive surface organometallic complexes observed using dynamic nuclear
      polarization surface enhanced NMR spectroscopy.
AB  - Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy (DNP SENS) is an
      emerging technique that allows access to high-sensitivity NMR spectra from
      surfaces. However, DNP SENS usually requires the use of radicals as an exogenous
      source of polarization, which has so far limited applications for organometallic
      surface species to those that do not react with the radicals. Here we show that
      reactive surface species can be studied if they are immobilized inside porous
      materials with suitably small windows, and if bulky nitroxide bi-radicals (here
      TEKPol) are used as the polarization source and which cannot enter the pores. The
      method is demonstrated by obtaining significant DNP enhancements from highly
      reactive complelxes [( 0000000000000000000000000000000000
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      0000000000000000000000000000000000 Si-O-)W(Me)5] supported on MCM-41, and effects
      of pore size (6.0, 3.0 and 2.5 nm) on the performance are discussed.

PMID- 28451175
TI  - Controllable NO release from Cu1.6S nanoparticle decomposition of S
      nitrosoglutathiones following photothermal disintegration of polymersomes to
      elicit cerebral vasodilatory activity.
AB  - Since the discovery of nitric oxide (NO) as a vasodilator, numerous NO therapies
      have been attempted to remedy disorders related to pathological vasoconstriction
      such as coronary artery disease. Despite the advances, clinical applications of
      NO therapies remain limited mainly because of the low stability of molecular NO
      donors (and NO molecules), and concerns about the increased oxidative stress and
      reduced arterial pressure associated with the systemic administration of NO. Here
      we design a photo-responsive polymersome with nitrosothiols and Cu1.6S
      nanoparticles in its core and shell, respectively, and demonstrate the photo
      triggered release of NO and its vasodilatory activity on zebrafish. Unlike
      conventional approaches, our design enhances the stability of NO donors and
      prospectively enables spatiotemporal regulation of NO release, thus minimizing
      the harmful effects associated with conventional NO therapies. We anticipate that
      such a strategy will open up new clinical applications of NO and help reveal the
      complex biological effects of NO in vivo.

PMID- 28451176
TI  - On the molecular mechanisms for the H2/CO2 separation performance of zeolite
      imidazolate framework two-layered membranes.
AB  - Double-layered zeolitic imidazolate framework (ZIF) membranes were fabricated
      inside polyimide P84 hollow fibers by a step-synthesis conducted by microfluidic
      technology and applied to pre-combustion gas separation. Our hypothesis, based on
      the information provided by a combination of molecular simulation and
      experiments, is that a CO2 adsorption reduction on the surface of the ZIF-9 would
      enhance the molecular sieving effect of this ZIF-9 layer and therefore the
      selectivity in the H2/CO2 mixture separation of the entire membrane. This
      reduction would be achieved by means of a less-CO2-adsorptive methylimidazolate
      based ZIF-67 or ZIF-8 layer coating the ZIF-9. ZIF-8/ZIF-9 and ZIF-67/ZIF-9
      double-layered membranes were prepared and characterized by XRD, FTIR, SEM, FIB,
      TEM and EDS. This unprecedented strategy led to a H2/CO2 separation selectivity
      of 9.6 together with a 250 GPU H2 permeance at 150  degrees C, showing a
      significant improvement with respect to the pure ZIF-9 membrane. Double-layered
      membranes also showed higher apparent CO2 activation energies than single-layered
      membranes, attributable to a diminished adsorption.

PMID- 28451177
TI  - Zirconocene catalyzed diastereoselective carbometalation of cyclobutenes.
AB  - The regio- and diastereoselective zirconocene-catalyzed carbomagnesiation of
      cyclobutenes is herein reported to afford configurationally stable
      cyclobutylmagnesium species that could subsequently react with a large variety of
      electrophiles to give polysubstituted cyclobutane species as a single
      diastereoisomer.

PMID- 28451178
TI  - Janus second-order nonlinear optical dendrimers: their controllable molecular
      topology and corresponding largely enhanced performance.
AB  - A new type of Janus dendrimers, consisting of two different side dendrons with
      the dipole orientation of the second-order nonlinear optical (NLO) chromophore
      moieties partially in a non-centrosymmetric direction, was intelligently designed
      and synthesized in order to enhance the macroscopic NLO performance and break
      through the limitation of NLO efficiency in the current molecular topological
      structure of azo chromophore-based polymers. This kind of Janus dendritic
      structure was constructed by the combination of convergent and divergent methods,
      with the utilization of a powerful "click chemistry reaction". The obtained three
      dendrimers, D-13N, D-17N and D-21N, show very high NLO performance, especially
      the dramatically enhanced NLO coefficient of 299 pm V-1 for D-13N, which is the
      highest value ever reported for polymers containing a simple azo chromophore. The
      new dendrimers provide a clear structure-properties relationship between high NLO
      efficiency and the controllable molecular topology with the non-centrosymmetrical
      alignment of dipole orientation, thus opening up a new avenue for the further
      development of NLO dendrimers with high performance and more importantly
      providing some clues for the rational design of functional dendrimers with
      controllable molecular topology.

PMID- 28451179
TI  - Luminescent ion pairs with tunable emission colors for light-emitting devices and
      electrochromic switches.
AB  - Most recently, stimuli-responsive luminescent materials have attracted increasing
      interest because they can exhibit tunable emissive properties which are sensitive
      to external physical stimuli, such as light, temperature, force, and electric
      field. Among these stimuli, electric field is an important external stimulus.
      However, examples of electrochromic luminescent materials that exhibit emission
      color change induced by an electric field are limited. Herein, we have proposed a
      new strategy to develop electrochromic luminescent materials based on luminescent
      ion pairs. Six tunable emissive ion pairs (IP1-IP6) based on iridium(iii)
      complexes have been designed and synthesized. The emission spectra of ion pairs
      (IPs) show concentration dependence and the energy transfer process is very
      efficient between positive and negative ions. Interestingly, IP6 displayed white
      emission at a certain concentration in solution or solid state. Thus, in this
      contribution, UV-chip (365 nm) excited light-emitting diodes showing orange,
      light yellow and white emission colors were successfully fabricated. Furthermore,
      IPs displayed tunable and reversible electrochromic luminescence. For example,
      upon applying a voltage of 3 V onto the electrodes, the emission color of the
      solution of IP1 near the anode or cathode changed from yellow to red or green,
      respectively. Color tunable electrochromic luminescence has also been realized by
      using other IPs. Finally, a solid-film electrochromic switch device with a
      sandwiched structure using IP1 has been fabricated successfully, which exhibited
      fast and reversible emission color change.

PMID- 28451180
TI  - Photochromic Torsional Switch (PTS): a light-driven actuator for the dynamic
      tuning of pi-conjugation extension.
AB  - Here we present a molecular architecture that can reversibly change the geometric
      conformation of its pi-system backbone via irradiation with two different
      wavelengths. The proposed 'molecular actuator' consists of a photoswitchable
      azobenzene orthogonally connected to a pi-conjugated bithiophene by both direct
      and aliphatic linker-assisted bonding. Upon exposure to 350 nm light, the trans
      azobenzene moiety isomerizes to its cis form, causing the bithiophene to assume a
      semiplanar anti conformation (extended pi-conjugation). Exposure to 254 nm light
      promotes the isomerization of the azobenzene unit back to its initial extended
      trans conformation, thus forcing the bithiophene fragment to twist out of
      coplanarity (restricted pi-conjugation). The molecular conformation of the
      bithiophene was characterized using steady-state UV-vis and nuclear magnetic
      resonance spectroscopy, as well as ab initio computations. The proposed molecular
      design could be envisaged as a pi-conjugation modulator, which has potential to
      be incorporated into extended linear pi-systems, i.e. via the terminal alpha
      thiophene positions, and used to tune their optical and electronic properties.

PMID- 28451181
TI  - Decoupling stability and release in disulfide bonds with antibody-small molecule
      conjugates.
AB  - Disulfide bonds provide a bioactivatable connection with applications in imaging
      and therapy. The circulation stability and intracellular release of disulfides
      are problematically coupled in that increasing stability causes a corresponding
      decrease in cleavage and payload release. However, an antibody offers the
      potential for a reversible stabilization. We examined this by attaching a small
      molecule directly to engineered cysteines in an antibody. At certain sites this
      unhindered disulfide was stable in circulation yet cellular internalization and
      antibody catabolism generated a disulfide catabolite that was rapidly reduced. We
      demonstrated that this stable connection and facile release is applicable to a
      variety of payloads. The ability to reversibly stabilize a labile functional
      group with an antibody may offer a way to improve targeted probes and
      therapeutics.

PMID- 28451182
TI  - The GTPase hGBP1 converts GTP to GMP in two steps via proton shuttle mechanisms.
AB  - GTPases play a crucial role in the regulation of many biological processes by
      catalyzing the hydrolysis of GTP into GDP. The focus of this work is on the
      dynamin-related large GTPase human guanine nucleotide binding protein-1 (hGBP1)
      which is able to hydrolyze GTP even to GMP. Here, we studied the largely unknown
      mechanisms of both GTP and GDP hydrolysis steps utilizing accelerated ab initio
      QM/MM metadynamics simulations to compute multi-dimensional free energy
      landscapes. We find an indirect substrate-assisted catalysis (SAC) mechanism for
      GTP hydrolysis involving transfer of a proton from the water nucleophile to a
      nonbridging phosphoryl oxygen via a proton relay pathway where the rate
      determining first step is concerted-dissociative nature. A "composite base"
      consisting of Ser73, Glu99, a bridging water molecule, and GTP was found to
      activate the nucleophilic water, thus disclosing the complex nature of the
      general base in hGBP1. A nearly two-fold reduction in the free energy barrier was
      obtained for GTP hydrolysis in the enzyme in comparison to bulk solvent. The
      subsequent GDP hydrolysis in hGBP1 was also found to follow a water-mediated
      proton shuttle mechanism. It is expected that the proton shuttle mechanisms
      unravelled for hGBP1 apply to many classes of GTPases/ATPases that possess an
      optimally-arranged hydrogen bonding network, which connects the catalytic water
      to a proton acceptor.

PMID- 28451183
TI  - Keto-polymethines: a versatile class of dyes with outstanding spectroscopic
      properties for in cellulo and in vivo two-photon microscopy imaging.
AB  - The synthesis of keto-heptamethine derivatives has been expanded to various new
      symmetrical and asymmetrical structures, including an unprecedented di-anionic
      keto-polymethine. The spectroscopic behavior of these new dyes has been
      systematically and thoroughly investigated, revealing that the formation of
      hydrogen bond interactions with protic solvents is responsible for a dramatic
      enhancement of the fluorescence quantum yield in the far-red spectral region. The
      existence of these strong hydrogen-bond interactions was further confirmed by
      molecular dynamics simulations. These bis-dipolar polymethines exhibit large two
      photon absorption (TPA) cross-sections (sigma2 in GM) in the near-infrared,
      making them ideal candidates for NIR-to-NIR two-photon microscopy imaging
      applications. We demonstrate that the molecular engineering of the
      hydrophilic/hydrophobic balance enables targeting of different cellular
      components, such as cytoplasm or cell membranes. Addition of appropriate
      substituents provides the molecule with high-water-solubility, affording
      efficient two-photon probes for angiography.

PMID- 28451185
TI  - Sizing the role of London dispersion in the dissociation of all-meta tert-butyl
      hexaphenylethane.
AB  - The structure and dynamics of enigmatic hexa(3,5-di-tert-butylphenyl)ethane was
      characterized via NMR spectroscopy for the first time. Our variable temperature
      NMR analysis demonstrates an enthalpy-entropy compensation that results in a
      vanishingly low dissociation energy (DeltaG298d = -1.60(6) kcal mol-1). An in
      silico study of increasingly larger all-meta alkyl substituted hexaphenylethane
      derivatives (Me, iPr, t Bu, Cy, 1-Ad) reveals a non-intuitive correlation between
      increased dimer stability with increasing steric crowding. This stabilization
      originates from London dispersion as expressed through the increasing
      polarizability of the alkyl substituents. Substitution with conformationally
      flexible hydrocarbon moieties, e.g., cyclohexyl, introduces large unfavourable
      entropy contributions. Therefore, using rigid alkyl groups like tert-butyl or
      adamantyl as dispersion energy donors (DED) is essential to help stabilize
      extraordinary bonding situations.

PMID- 28451184
TI  - Combatting AMR: photoactivatable ruthenium(ii)-isoniazid complex exhibits rapid
      selective antimycobacterial activity.
AB  - The novel photoactive ruthenium(ii) complex cis-[Ru(bpy)2(INH)2][PF6]2 (1.2PF6,
      INH = isoniazid) was designed to incorporate the anti-tuberculosis drug,
      isoniazid, that could be released from the Ru(ii) cage by photoactivation with
      visible light. In aqueous solution, 1 rapidly released two equivalents of
      isoniazid and formed the photoproduct cis-[Ru(bpy)2(H2O)2]2+ upon irradiation
      with 465 nm blue light. We screened for activity against bacteria containing the
      three major classes of cell envelope: Gram-positive Bacillus subtilis, Gram
      negative Escherichia coli, and Mycobacterium smegmatis in vitro using blue and
      multi-colored LED multi-well arrays. Complex 1 is inactive in the dark, but when
      photoactivated is 5.5* more potent towards M. smegmatis compared to the clinical
      drug isoniazid alone. Complementary pump-probe spectroscopy measurements along
      with density functional theory calculations reveal that the mono-aqua product is
      formed in <500 ps, likely facilitated by a 3MC state. Importantly, complex 1 is
      highly selective in killing mycobacteria versus normal human cells, towards which
      it is relatively non-toxic. This work suggests that photoactivatable prodrugs
      such as 1 are potentially powerful new agents in combatting the global problem of
      antibiotic resistance.

PMID- 28451186
TI  - Thioester reduction and aldehyde transamination are universal steps in
      actinobacterial polyketide alkaloid biosynthesis.
AB  - Actinobacteria produce a variety of polyketide alkaloids with unusual structures.
      Recently, it was shown that a type I modular polyketide synthase (PKS) is
      involved in the assembly of coelimycin P1, a polyketide alkaloid produced by
      Streptomyces coelicolor M145. However, the mechanisms for converting the product
      of the PKS to coelimycin P1 remain to be elucidated. Here we show that the C
      terminal thioester reductase (TR) domain of the PKS and an omega-transaminase are
      responsible for release of the polyketide chain as an aldehyde and its subsequent
      reductive amination. Bioinformatics analyses identified numerous gene clusters in
      actinobacterial genomes that encode modular PKSs with a C-terminal TR domain and
      a homolog of the omega-transaminase. These are predicted to direct the
      biosynthesis of both known and novel polyketide alkaloids, suggesting that
      reductive chain release and transamination constitutes a conserved mechanism for
      the biosynthesis of such metabolites.

PMID- 28451187
TI  - Dendritic polarizing agents for DNP SENS.
AB  - Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy (DNP SENS) is an
      effective method to significantly improve solid-state NMR investigation of solid
      surfaces. The presence of unpaired electrons (polarizing agents) is crucial for
      DNP, but it has drawbacks such as leading to faster nuclear spin relaxation, or
      even reaction with the substrate under investigation. The latter can be a
      particular problem for heterogeneous catalysts. Here, we present a series of
      carbosilane-based dendritic polarizing agents, in which the bulky dendrimer can
      reduce the interaction between the solid surface and the free radical. We thereby
      preserve long nuclear T'2 of the surface species, and even successfully enhance a
      reactive heterogeneous metathesis catalyst.

PMID- 28451188
TI  - Organic linkers control the thermosensitivity of the emission intensities from
      Tb(iii) and Eu(iii) in a chameleon polymer.
AB  - Thermometers whose emission color gradually changes with temperature are called
      chameleon emitters. In this study, we discuss the mechanism of the
      thermosensitivity of the emission color of polymers that contain two lanthanides
      (Ln3+), e.g., [Tb0.99Eu0.01(hfa)3(linker)] n , where the Ln3+(hfa)3 complexes
      (hfa: hexafluoro acetylacetonato) are connected by a phosphine oxide "linker"
      molecule. First, the difference in the thermosensitivities of the emissions from
      Tb3+ and Eu3+ are discussed. With increasing temperature, the green-emission
      intensity from Tb3+ decreases whereas the red-emission intensity from Eu3+ does
      not change. This was found to originate from the different reaction barriers for
      the quenching of the Ln3+ excited state via the intersystem crossing (ISC)
      between the hfa-centered triplet state and the ground state. Next, the excitation
      energy transfer (EET) from Tb3+ to Eu3+ is discussed. Although the direct EET
      between Ln3+ atoms is negligible because of the long distance between them,
      stepwise EET is found to occur via the linker-centered triplet state with a
      reasonable barrier. Thus, we propose a new idea-thermosensitivity can be
      controlled by the linker as well as by the ligand (hfa). To confirm the role of
      the linker, four phosphine oxides were examined. The thermosensitivity dependence
      on the linker is validated via experimental measurements.

PMID- 28451189
TI  - Depletion sphere: Explaining the number of Ag islands on Au nanoparticles.
AB  - We report multi-site nucleation and growth of Ag islands on colloidal Au
      nanoparticles. By modifying a single factor, a range of products from Janus
      nanoparticles to satellite nanostructures are obtained. The identification of
      these key factors reveals the correlation between the concentration gradient and
      the choice of nucleation sites. In contrast to the inhibited homogeneous
      nucleation in the bulk solution, we argue that the non-steady-state concentration
      gradient plays a critical role in inhibiting nucleation within nanometer distance
      during the initial stage of growth-an essential but not yet recognized factor in
      colloidal synthesis. A depletion sphere model was developed, so that the multi
      site nucleation is well integrated with the classic theory of nucleation and
      growth. Alternative explanations are carefully examined and ruled out. We believe
      that the synthetic know-how and the mechanistic insights can be broadly applied
      and are of importance to the advance of nanosynthesis.

PMID- 28451190
TI  - Achievement of visible-light-driven Z-scheme overall water splitting using barium
      modified Ta3N5 as a H2-evolving photocatalyst.
AB  - Ta3N5 is one of the most promising photocatalyst candidates for solar water
      splitting, but it still remains challenging to achieve overall water splitting
      via Ta3N5-based photocatalysts regardless of whether it uses a one step or two
      step method. Here we will address the relatively poor photocatalytic proton
      reduction of Ta3N5 with an effort for the promotion of charge separation via
      barium modification. One-pot nitridation of barium nitrate-impregnated Ta2O5
      precursor was adopted here for the synthesis of Ta3N5 accompanied with the
      creation of a Ta3N5/BaTaO2N heterostructure and surface passivation. Due to the
      synergetic effect of the improved interfacial charge separation and the decreased
      defect density, the photocatalytic H2 evolution rate of barium-modified Ta3N5 is
      effectively promoted. Encouraged by this, a visible-light-driven Z-scheme overall
      water splitting system was successfully constructed by using the barium-modified
      Ta3N5 as a H2-evolving photocatalyst, together with a PtO x /WO3 and IO3-/I- pair
      as an O2-evolving photocatalyst and a redox mediator, respectively.

PMID- 28451191
TI  - Construction of an octosyl acid backbone catalyzed by a radical S
      adenosylmethionine enzyme and a phosphatase in the biosynthesis of high-carbon
      sugar nucleoside antibiotics.
AB  - Unique bicyclic octosyl uronic acid nucleosides include ezomycin, malayamycin,
      and octosyl acid (OA). They are structurally characterized by OA, an unusual 8
      carbon furanosyl nucleoside core proposed to be the precursor to polyoxin and
      nikkomycin. Despite the well-known bioactivity of these nucleoside antibiotics,
      the biosynthesis of OA has not been elucidated yet. Here we report the two
      pivotal enzymatic steps in the polyoxin biosynthetic pathway leading to the
      identification of OA as a key intermediate. Our data suggest that this
      intermediate is formed via a free radical reaction catalyzed by the radical S
      adenosylmethionine (SAM) enzyme, PolH, and using 3'-enolpyruvyl uridine 5'
      monophosphate (3'-EUMP) as a substrate. Subsequent dephosphorylation catalyzed by
      phosphatase PolJ converts the resulting octosyl acid 5'-phosphate (OAP) to OA.
      These results provide, for the first time, significant in vitro evidence for the
      biosynthetic origins of the C8 backbone of OA.

PMID- 28451192
TI  - Selective transition-metal-free vicinal cis-dihydroxylation of saturated
      hydrocarbons.
AB  - A transition-metal-free cis-dihydroxylation of saturated hydrocarbons under
      ambient reaction conditions has been developed. The described approach allows a
      direct and selective synthesis of vicinal diols. The new reaction thereby
      proceeds via radical iodination and a sequence of oxidation steps. A broad scope
      of one-pot dual C(sp3)-H bond functionalization for the selective synthesis of
      vicinal syn-diols was demonstrated.

PMID- 28451193
TI  - Proton-coupled electron transfer in the electrocatalysis of CO2 reduction:
      prediction of sequential vs. concerted pathways using DFT.
AB  - Herein we investigate computationally in detail the mechanism of the formation of
      the carboxylate adduct during the electroreduction of CO2 in water catalysed by
      cobalt porphyrin complexes. Specifically, we address qualitatively the
      competition between the concerted and sequential pathways for the proton-coupled
      electron transfer. We use a simple methodology for accurate computation of the
      pKa of the neutral and anionic carboxylate intermediates, [CoP-COOH] and [CoP
      COOH]- (where CoP is a cobalt porphine complex), based on the isodesmic proton
      exchange reaction scheme. The predicted values are used as in input for a
      theoretical model that describes the transition between the sequential and
      concerted pathways. The activation of the sequential pathway (ET-PT) that leads
      to the formation of the neutral [CoP-COOH] intermediate at pH ~ 3.5 (pKa[CoP
      COOH] = 3.5 +/- 0.4), as predicted by the calculations, is in good agreement with
      the drastic increase in the faradaic efficiency of the CO2 reduction reaction
      towards CO at pH = 3 compared to pH = 1, as experimentally observed. This
      confirms the existence of the CO2 anionic adduct [CoP-CO2]- as a viable
      intermediate at pH = 3 and its crucial role for the pH dependence of the faradaic
      efficiency for the CO2 reduction. The analysis also shows that when the pH is
      significantly higher than the pKa of the neutral carboxylate adduct, the CO2
      reduction has to go through an alternative pathway with the formation of the
      anionic carboxylate intermediate [CoP-COOH]-. It is formed through a concerted
      proton-electron transfer step from the anionic CO2 adduct [CoP-CO2]- when the pH
      is below ~8.6 (pKa[CoP-COOH]- = 8.6 +/- 0.4). At pH ~ 8.6 and above, another
      decoupled ET-PT is predicted to take place, leading to the formation of a
      dianionic CO2 adduct [CoP-CO2]2-.

PMID- 28451194
TI  - Modulating the phases of iron carbide nanoparticles: from a perspective of
      interfering with the carbon penetration of Fe@Fe3O4 by selectively adsorbed
      halide ions.
AB  - Iron carbide nanoparticles (ICNPs) are considered to have great potential in new
      energy conversion, nanomagnets and biomedical applications due to their
      intrinsically peculiar magnetic and catalytic properties. However, the synthetic
      routes were greatly limited in morphology and phase controlled synthesis. In this
      article, we present a versatile solution chemistry route towards colloidal ICNPs
      (Fe2C-hexagonal and monoclinic syngony, Fe5C2-monoclinic syngony and Fe3C
      orthorhombic syngony) derived from body centered cubic Fe@Fe3O4 by introducing
      heteroatoms to restrain their phase transformation. We found that the phases of
      Fe2C NPs could be controlled by direct phase transformation in the drastic
      thermally driven procedure (defined as thermodynamical manner). Meanwhile, the
      selective adsorption of Cl ions weakened the bonding between Fe and C atoms, thus
      interfering with the penetration of C atoms to form lower carbon content Fe5C2
      and Fe3C NPs. The kinetic mechanisms were evaluated using density functional
      theory (DFT) simulations focusing on the bonding energy between Fe-C and Fe-Cl
      atoms. All the obtained ICNPs exhibited typically soft ferromagnetic properties
      with the highest saturation magnetization value of 101.2 emu g-1 and the highest
      Curie temperature of 497.8 K.

PMID- 28451195
TI  - The stereodivergent formation of 2,6-cis and 2,6-trans-tetrahydropyrans:
      experimental and computational investigation of the mechanism of a thioester oxy
      Michael cyclization.
AB  - The origins of the stereodivergence in the thioester oxy-Michael cyclization for
      the formation of 4-hydroxy-2,6-cis- or 2,6-trans-substituted tetrahydropyran
      rings under different conditions was investigated both computationally and
      experimentally. Synthetic studies showed that the 4-hydroxyl group was essential
      for stereodivergence. When the 4-hydroxyl group was present, TBAF-mediated
      conditions gave the 2,6-trans-tetrahydropyran and trifluoroacetic acid-mediated
      conditions gave the 2,6-cis-tetrahydropyran. This stereodivergence vanished when
      the hydroxyl group was removed or protected. Computational studies revealed that:
      (i) the trifluoroacetic acid catalysed formation of 2,6-cis-tetrahydropyrans was
      mediated by a trifluoroacetate-hydroxonium bridge and proceeded via a chair-like
      transition state; (ii) the TBAF-mediated formation of 2,6-trans-tetrahydropyrans
      proceeded via a boat-like transition state, where the 4-hydroxyl group formed a
      crucial hydrogen bond to the cyclizing alkoxide; (iii) both reactions are under
      kinetic control. The utility of this stereodivergent approach for the formation
      of 4-hydroxy-2,6-substituted tetrahydropyran rings has been demonstrated by the
      total syntheses of the anti-osteoporotic natural products diospongin A and B.

PMID- 28451196
TI  - Ion-pair recognition by a neutral [2]rotaxane based on a bis-calix[4]pyrrole
      cyclic component.
AB  - In this work, we report our investigations on the synthesis of a [2]rotaxane
      based on a bis(calix[4]pyrrole) cyclic component and a 3,5-bis-amidepyridyl-N
      oxide derivative axle. We isolated the [2]rotaxane in a significant 50% yield
      through an optimized "in situ" capping strategy using the copper(i)-catalyzed
      azide-alkyne cycloaddition reaction. The synthetic precursor of the [2]rotaxane,
      featuring [2]pseudorotaxane topology, could be quantitatively assembled in
      solution in the presence of one equivalent of tetrabutylammonium chloride or
      cyanate salts producing a four-particle aggregate. However, we observed that the
      addition of the salt was deleterious not only for the isolation of the
      [2]rotaxane in its pure form but, more important, for the optimal performance of
      the copper catalyst. We probed the interaction of the prepared [2]rotaxane with
      tetraalkylammonium salts of chloride, nitrate and cyanate anions by means of 1H
      NMR titrations and ITC experiments. We show that in chloroform solution the
      [2]rotaxane functions as an efficient heteroditopic receptor for the salts
      forming thermodynamically and kinetically highly stable ion-paired complexes with
      1 : 1 stoichiometry. At millimolar concentration and using 1H NMR spectroscopy we
      observed that the addition of more than 1 equiv. of the salt induced the gradual
      disassembly of the 1 : 1 complex of the [2]rotaxane and the concomitant formation
      of higher stoichiometry aggregates i.e. 2 : 1 complexes.

PMID- 28451197
TI  - Copper carbenes alkylate guanine chemoselectively through a substrate directed
      reaction.
AB  - Cu(i) carbenes derived from alpha-diazocarbonyl compounds lead to selective
      alkylation of the O6 position in guanine (O6-G) in mono- and oligonucleotides.
      Only purine-type lactam oxygens are targeted - other types of amides or lactams
      are poorly reactive under conditions that give smooth alkylation of guanine.
      Mechanistic studies point to N7G as a directing group that controls selectivity.
      Given the importance of O6-G adducts in biology and biotechnology we expect that
      Cu(i)-catalyzed O6-G alkylation will be a broadly used synthetic tool. While the
      propensity for transition metals to increase redox damage is well-appreciated,
      our results suggest that transition metals might also increase the vulnerability
      of nucleic acids to alkylation damage.

PMID- 28451198
TI  - Manipulating charge transfer excited state relaxation and spin crossover in iron
      coordination complexes with ligand substitution.
AB  - Developing light-harvesting and photocatalytic molecules made with iron could
      provide a cost effective, scalable, and environmentally benign path for solar
      energy conversion. To date these developments have been limited by the sub
      picosecond metal-to-ligand charge transfer (MLCT) electronic excited state
      lifetime of iron based complexes due to spin crossover - the extremely fast
      intersystem crossing and internal conversion to high spin metal-centered excited
      states. We revitalize a 30 year old synthetic strategy for extending the MLCT
      excited state lifetimes of iron complexes by making mixed ligand iron complexes
      with four cyanide (CN-) ligands and one 2,2'-bipyridine (bpy) ligand. This
      enables MLCT excited state and metal-centered excited state energies to be
      manipulated with partial independence and provides a path to suppressing spin
      crossover. We have combined X-ray Free-Electron Laser (XFEL) Kbeta hard X-ray
      fluorescence spectroscopy with femtosecond time-resolved UV-visible absorption
      spectroscopy to characterize the electronic excited state dynamics initiated by
      MLCT excitation of [Fe(CN)4(bpy)]2-. The two experimental techniques are highly
      complementary; the time-resolved UV-visible measurement probes allowed electronic
      transitions between valence states making it sensitive to ligand-centered
      electronic states such as MLCT states, whereas the Kbeta fluorescence
      spectroscopy provides a sensitive measure of changes in the Fe spin state
      characteristic of metal-centered excited states. We conclude that the MLCT
      excited state of [Fe(CN)4(bpy)]2- decays with roughly a 20 ps lifetime without
      undergoing spin crossover, exceeding the MLCT excited state lifetime of [Fe(2,2'
      bipyridine)3]2+ by more than two orders of magnitude.

PMID- 28451199
TI  - Enantiodivergent Steglich rearrangement of O-carboxylazlactones catalyzed by a
      chirality switchable helicene containing a 4-aminopyridine unit.
AB  - A pseudo-enantiomeric pair of optically switchable helicenes containing a
      catalytic 4-N-methylaminopyridine (MAP) bottom unit and a C2-symmetric, (10R,11R)
      dimethoxymethyl-dibenzosuberane top template was synthesized. They underwent
      complementary photoswitching at 290 nm (P/M', <1/>99) and 340 nm (P/M', 91/9) and
      unidirectional thermo-rotation at 130  degrees C (P/M', >99/<1). They were
      utilized to catalyze enantiodivergent Steglich rearrangement of O- to C
      carboxylazlactones, with formation of either enantiomer with up to 91% ee (R) and
      94% ee (S), respectively.

PMID- 28451200
TI  - C(sp3)-C(sp2) cross-coupling of alkylsilicates with borylated aryl bromides - an
      iterative platform to alkylated aryl- and heteroaryl boronates.
AB  - The attractive field of iterative cross-coupling has seen numerous advances,
      although almost exclusively in the union of sp2-hybridized partners.
      Conspicuously absent from this useful synthetic manifold is the inclusion of sp3
      hybridized pronucleophiles that can undergo transmetalation under mild
      conditions. Described here is the use of primary and secondary ammonium
      alkylsilicates, which undergo facile C(sp3)-C(sp2) cross-coupling with borylated
      aryl bromide partners under photoredox/nickel dual catalysis conditions. This
      operationally simple procedure allows the production of alkylated small molecules
      possessing boronate ester (BPin, Bneopentyl, BMIDA) functional handles. Because
      of the extremely mild reaction conditions and the innocuous byproduct generated
      upon fragmentative oxidation of silicates, the corresponding borylated compounds
      were isolated in good to excellent yields. Aryl bromides bearing unprotected
      boronic acids are also generally tolerated for the first time and prove useful in
      multistep syntheses. Unlike many previously reported photoredox/Ni dual cross
      couplings, the C(sp3)-C(sp2) bonds were forged using a transition metal-free
      photocatalyst, allowing a substantial increase in sustainability as well as a
      cost reduction. Because the developed Ni-catalyzed cross-coupling does not
      require discrete boron speciation control, as in many popular orthogonal Pd-based
      methods, this protocol represents a significant advance in atom- and step
      economy.

PMID- 28451201
TI  - Sequential catalysis: exploiting a single rhodium(i) catalyst to promote an
      alkyne hydroacylation-aryl boronic acid conjugate addition sequence.
AB  - We demonstrate that a single Rh(i) complex can promote two mechanistically
      distinct C-C bond-forming reactions - alkyne hydroacylation and aryl boronic acid
      conjugate addition - to deliver substituted ketone products from the controlled
      assembly of three readily available fragments. This is a rare example of a
      Rh(i)/Rh(iii) cycle and a redox neutral Rh(i) cycle being promoted by a single
      catalyst. The process is broad in scope, allowing significant variation of all
      three reaction components. Incorporation of an enantiomerically pure bis
      phosphine ligand renders the process enantioselective. Superior levels of
      enantioselectivity (up to >99% ee) can be achieved from using a two catalyst
      system, whereby two Rh(i) complexes, one incorporating an achiral bis-phosphine
      ligand and the second a chiral diene ligand, are introduced at the start of the
      reaction sequence.

PMID- 28451202
TI  - Specific protein labeling with caged fluorophores for dual-color imaging and
      super-resolution microscopy in living cells.
AB  - We present new fluorophore-conjugates for dual-color photoactivation and super
      resolution imaging inside live mammalian cells. These custom-designed, photo
      caged Q-rhodamines and fluoresceins are cell-permeable, bright and localize
      specifically to intracellular targets. We utilized established orthogonal protein
      labeling strategies to precisely attach the photoactivatable fluorophores to
      proteins with subsequent activation of fluorescence by irradiation with UV light.
      That way, diffusive cytosolic proteins, histone proteins as well as filigree
      mitochondrial networks and focal adhesion proteins were visualized inside living
      cells. We applied the new photoactivatable probes in inverse fluorescence
      recovery after photo-bleaching (iFRAP) experiments, gaining real-time access to
      protein dynamics from live biological settings with resolution in space and time.
      Finally, we used the caged Q-rhodamine for photo-activated localization
      microscopy (PALM) on both fixed and live mammalian cells, where the superior
      molecular brightness and photo-stability directly resulted in improved
      localization precisions for different protein targets.

PMID- 28451203
TI  - Iron supported on bioinspired green silica for water remediation.
AB  - Iron has been used previously in water decontamination, either unsupported or
      supported on clays, polymers, carbons or ceramics such as silica. However, the
      reported synthesis procedures are tedious, lengthy (involving various steps), and
      either utilise or produce toxic chemicals. Herein, the use of a simple, rapid,
      bio-inspired green synthesis method is reported to prepare, for the first time, a
      family of iron supported on green nanosilica materials (Fe@GN) to create new
      technological solutions for water remediation. In particular, Fe@GN were employed
      for the removal of arsenate ions as a model for potentially toxic elements in
      aqueous solution. Several characterization techniques were used to study the
      physical, structural and chemical properties of the new Fe@GN. When evaluated as
      an adsorption platform for the removal of arsenate ions, Fe@GN exhibited high
      adsorption capacity (69 mg of As per g of Fe@GN) with superior kinetics (reaching
      ~35 mg As per g sorbent per hr) - threefold higher than the highest removal rates
      reported to date. Moreover, a method was developed to regenerate the Fe@GN
      allowing for a full recovery and reuse of the adsorbent in subsequent
      extractions; strongly highlighting the potential technological benefits of these
      new green materials.

PMID- 28451205
TI  - Effect of pore size and shape on the thermal conductivity of metal-organic
      frameworks.
AB  - We investigate the effect of pore size and shape on the thermal conductivity of a
      series of idealized metal-organic frameworks (MOFs) containing adsorbed gas using
      molecular simulations. With no gas present, the thermal conductivity decreases
      with increasing pore size. In the presence of adsorbed gas, MOFs with smaller
      pores experience reduced thermal conductivity due to phonon scattering introduced
      by gas-crystal interactions. In contrast, for larger pores (>1.7 nm), the
      adsorbed gas does not significantly affect thermal conductivity. This difference
      is due to the decreased probability of gas-crystal collisions in larger pore
      structures. In contrast to MOFs with simple cubic pores, the thermal conductivity
      in structures with triangular and hexagonal pore channels exhibits significant
      anisotropy. For different pore geometries at the same atomic density, hexagonal
      channel MOFs have both the highest and lowest thermal conductivities, along and
      across the channel direction, respectively. In the triangular and hexagonal
      channeled structures, the presence of gas molecules has different effects on
      thermal conductivity along different crystallographic directions.

PMID- 28451204
TI  - Organic solid fluorophores regulated by subtle structure modification: color
      tunable and aggregation-induced emission.
AB  - Organic solid fluorophores with a tunable emission color have been widely applied
      in multiple areas. However, rational design and efficient crafting of these
      fluorophores from a simple core skeleton is still a formidable challenge because
      of the undesirable concentration quenching emission effect. Herein, we present
      the development of two series of organic solid fluorophores based on a backbone
      of p-bis(2,2-dicyanovinyl)benzene. Notably, the introduction of either non
      aromatic or aromatic substituents provides fluorophores with a tunable emission
      color. Moreover, the fluorophores with aromatic substituents exhibit additional
      unique optical phenomena, such as aggregation-induced emission, polymorphism
      dependent emission, and reversible mechanochromic luminescence.

PMID- 28451206
TI  - Layered host-guest long-afterglow ultrathin nanosheets: high-efficiency
      phosphorescence energy transfer at 2D confined interface.
AB  - Tuning and optimizing the efficiency of light energy transfer play an important
      role in meeting modern challenges of minimizing energy loss and developing high
      performance optoelectronic materials. However, attempts to fabricate systems
      giving highly efficient energy transfer between luminescent donor and acceptor
      have achieved limited success to date. Herein, we present a strategy towards
      phosphorescence energy transfer at a 2D orderly crystalline interface. We first
      show that new ultrathin nanosheet materials giving long-afterglow luminescence
      can be obtained by assembling aromatic guests into a layered double hydroxide
      host. Furthermore, we demonstrate that co-assembly of these long-lived energy
      donors with an energy acceptor in the same host generates an ordered arrangement
      of phosphorescent donor-acceptor pairs spatially confined within the 2D
      nanogallery, which affords energy transfer efficiency as high as 99.7%.
      Therefore, this work offers an alternative route to develop new types of long
      afterglow nanohybrids and efficient light transfer systems with potential energy,
      illumination and sensor applications.

PMID- 28451207
TI  - Enantioselective bifunctional iminophosphorane catalyzed sulfa-Michael addition
      of alkyl thiols to unactivated beta-substituted-alpha,beta-unsaturated esters.
AB  - The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated
      beta-substituted-alpha,beta-unsaturated esters catalyzed by a bifunctional
      iminophosphorane (BIMP) organocatalyst is described. The low acidity of the alkyl
      thiol pro-nucleophiles is overcome by the high Bronsted basicity of the catalyst
      and the chiral scaffold/thiourea hydrogen-bond donor moiety provides the required
      enantiofacial discrimination in the addition step. The reaction is broad in scope
      with respect to the alkyl thiol and beta-substituent of the alpha,beta
      unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%)
      and enantioselectivity (up to 97 : 3 er) and can operate down to 1 mol% catalyst
      loading.

PMID- 28451208
TI  - Optical control of AMPA receptors using a photoswitchable quinoxaline-2,3-dione
      antagonist.
AB  - AMPA receptors respond to the neurotransmitter glutamate and play a critical role
      in excitatory neurotransmission. They have been implicated in several psychiatric
      disorders and have rich pharmacology. Antagonists of AMPA receptors have been
      explored as drugs and one has even reached the clinic. We now introduce a freely
      diffusible photoswitchable antagonist that is selective for AMPA receptors and
      endows them with light-sensitivity. Our photoswitch, ShuBQX-3, is active in its
      dark-adapted trans-isoform but is significantly less active as its cis-isoform.
      ShuBQX-3 exhibits a remarkable red-shifting of its photoswitching properties
      through interactions with the AMPA receptor ligand binding site. Since it can be
      used to control action potential firing with light, it could emerge as a powerful
      tool for studying synaptic transmission with high spatial and temporal precision.

PMID- 28451209
TI  - Reagent-controlled enantioselectivity switch for the asymmetric fluorination of
      beta-ketocarbonyls by chiral primary amine catalysis.
AB  - A reagent-controlled enantioselectivity switch was uncovered in the asymmetric
      alpha-fluorination of beta-ketocarbonyls by a chiral primary amine catalyst. By a
      simple swap of fluorination reagents, both enantiomers of the quaternary
      fluorination adducts could be obtained with good yields and high
      enantioselectivity. Mechanistic studies disclosed dual H-bonding and
      electrostatic stereocontrolling modes for the catalysis.

PMID- 28451210
TI  - Enantioselective allylic alkylation of stereodefined polysubstituted copper
      enolates as an entry to acyclic quaternary carbon stereocentres.
AB  - A sequence of regio- and stereoselective carbometalation followed by oxidation of
      ynamides leads to stereodefined fully substituted enolates that subsequently
      react with various functionalized allyl bromide reagents to provide the expected
      products possessing an enantiomerically pure quaternary carbon stereocentre in
      the alpha-position to the carbonyl group in excellent yields and enantiomeric
      ratios after cleavage of the oxazolidinone moiety. Three new bonds are formed in
      a single-pot operation.

PMID- 28451212
TI  - Two exfoliation approaches for organic layered compounds: hydrophilic and
      hydrophobic polydiacetylene nanosheets.
AB  - Nanosheets have attracted much interest because of their characteristic
      properties originating from anisotropic and flexible structures. Inorganic
      nanosheets are synthesized from precursor layered compounds through exfoliation
      in a liquid phase. In contrast, a versatile exfoliation approach has not been
      fully studied for organic layered compounds. Here we report two exfoliation
      approaches for organic layered compounds. Hydrophilic and hydrophobic
      polydiacetylene (PDA) nanosheets, around 5 nm in thickness, are obtained through
      exfoliation of the layered precursor in aqueous and nonpolar organic media,
      respectively. The intercalation of ions and molecules in the interlayer space
      facilitates swelling and exfoliation. The resultant PDA nanosheets showed
      characteristic photochemical properties originating from the flexible structure.
      The exfoliation approach can be applied to a variety of organic layered compounds
      for the generation of designed nanosheets.

PMID- 28451211
TI  - Acyclic quaternary centers from asymmetric conjugate addition of alkylzirconium
      reagents to linear trisubstituted enones.
AB  - Synthetic methods for the selective formation of all carbon quaternary centres in
      non-cyclic systems are rare. Here we report highly enantioselective Cu-catalytic
      asymmetric conjugate addition of alkylzirconium species to twelve different
      acyclic trisubstituted enones. A variety of sp3-hybridized nucleophiles generated
      by in situ hydrozirconation of alkenes with the Schwartz reagent can be
      introduced, giving linear products bearing quaternary centres with up to 98% ee.
      The method is tolerant of several important functional groups and 27 total
      examples are reported. The method uses a new chiral nonracemic phosphoramidite
      ligand in a complex with copper triflate as the catalyst. This work allows the
      straightforward stereocontrolled formation of a valuable structural motif using
      only a catalytic amount of chiral reagent.

PMID- 28451213
TI  - Chromium photocatalysis: accessing structural complements to Diels-Alder adducts
      with electron-deficient dienophiles.
AB  - A chromium-catalyzed, visible light-activated net [4 + 2] cycloaddition between
      dienes and electron-deficient alkenes is described. Gathered evidence, via
      control experiments, isolated intermediates, and measured redox potentials,
      points to several converging reaction pathways that afford the cyclohexene
      adducts, including a photochemical [2 + 2] cycloaddition/vinylcyclobutane
      rearrangement cascade and a substrate excitation/oxidation sequence to a radical
      cation intermediate. Notably, the accompanying mechanistic stipulations result in
      a process that yields regioisomeric compounds from those generated by traditional
      Diels-Alder cycloadditions.

PMID- 28451214
TI  - Synthesis and properties of [8]-, [10]-, [12]-, and [16]cyclo-1,4-naphthylenes.
AB  - The synthesis and properties of various [n]cyclo-1,4-naphthylenes ([n]CNs, n = 8,
      10, 12, and 16) are described. Initially, extended L-shaped units, which could be
      converted into quater- or quinquenaphthylenes were prepared. Nickel- or palladium
      mediated couplings of these extended L-shaped units, followed by reductive
      aromatization of the coupling products afforded [8]-, [10]-, [12]-, and [16]CNs.
      The size-dependent photophysical properties of these CNs were confirmed by
      measuring their UV-vis absorption and fluorescence spectra. The theoretical
      studies supported substantial effects of the number of naphthalene rings on the
      structural and photophysical properties of these CNs. A kinetic study on the
      thermal conversion of the Cs-symmetric conformer of [10]CN into its most stable
      D5d-symmetric conformer indicated that ring strain affects the rotation barrier
      of the naphthalene rings in [10]CN.

PMID- 28451215
TI  - MnO2 nanosheet mediated "DD-A" FRET binary probes for sensitive detection of
      intracellular mRNA.
AB  - The donor donor-acceptor (DD-A) FRET model has proven to have a higher FRET
      efficiency than donor-acceptor acceptor (D-AA), donor-acceptor (D-A), and donor
      donor-acceptor acceptor (DD-AA) FRET models. The in-tube and in-cell experiments
      clearly demonstrate that the "DD-A" FRET binary probes can indeed increase the
      FRET efficiency and provide higher imaging contrast, which is about one order of
      magnitude higher than the ordinary "D-A" model. Furthermore, MnO2 nanosheets were
      employed to deliver these probes into living cells for intracellular TK1 mRNA
      detection because they can adsorb ssDNA probes, penetrate across the cell
      membrane and be reduced to Mn2+ ions by intracellular GSH. The results indicated
      that the MnO2 nanosheet mediated "DD-A" FRET binary probes are capable of
      sensitive and selective sensing gene expression and chemical-stimuli changes in
      gene expression levels in cancer cells. We believe that the MnO2 nanosheet
      mediated "DD-A" FRET binary probes have the potential as a simple but powerful
      tool for basic research and clinical diagnosis.

PMID- 28451216
TI  - A low-crystalline ruthenium nano-layer supported on praseodymium oxide as an
      active catalyst for ammonia synthesis.
AB  - Ammonia is a crucial chemical feedstock for fertilizer production and is a
      potential energy carrier. However, the current method of synthesizing ammonia,
      the Haber-Bosch process, consumes a great deal of energy. To reduce energy
      consumption, a process and a substance that can catalyze ammonia synthesis under
      mild conditions (low temperature and low pressure) are strongly needed. Here we
      show that Ru/Pr2O3 without any dopant catalyzes ammonia synthesis under mild
      conditions at 1.8 times the rates reported with other highly active catalysts.
      Scanning transmission electron micrograph observations and energy dispersive X
      ray analyses revealed the formation of low-crystalline nano-layers of ruthenium
      on the surface of Pr2O3. Furthermore, CO2 temperature-programmed desorption
      revealed that the catalyst was strongly basic. These unique structural and
      electronic characteristics are considered to synergistically accelerate the rate
      determining step of NH3 synthesis, cleavage of the N
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      expect that the use of this catalyst will be a starting point for achieving
      efficient ammonia synthesis.

PMID- 28451217
TI  - Aromatic sulfonation with sulfur trioxide: mechanism and kinetic model.
AB  - Electrophilic aromatic sulfonation of benzene with sulfur trioxide is studied
      with ab initio molecular dynamics simulations in gas phase, and in explicit
      noncomplexing (CCl3F) and complexing (CH3NO2) solvent models. We investigate
      different possible reaction pathways, the number of SO3 molecules participating
      in the reaction, and the influence of the solvent. Our simulations confirm the
      existence of a low-energy concerted pathway with formation of a cyclic transition
      state with two SO3 molecules. Based on the simulation results, we propose a
      sequence of elementary reaction steps and a kinetic model compatible with
      experimental data. Furthermore, a new alternative reaction pathway is proposed in
      complexing solvent, involving two SO3 and one CH3NO2.

PMID- 28451218
TI  - Bimetallic nanosized solids with acid and redox properties for catalytic
      activation of C-C and C-H bonds.
AB  - A new approach is presented to form self-supported bimetallic nanosized solids
      with acid and redox catalytic properties. They are water-, air- and H2-stable,
      and are able to activate demanding C-C and C-H reactions. A detailed mechanistic
      study on the formation of the Ag-Fe bimetallic system shows that a rapid redox
      coupled sequence between Ag+, O2 (air) and Fe2+ occurs, giving monodisperse Ag
      nanoparticles supported by O-bridged diatomic Fe3+ triflimides. The system can be
      expanded to Ag nanoparticles embedded within a matrix of Cu2+, Bi3+ and Yb3+
      triflimide.

PMID- 28451219
TI  - Total synthesis of malagashanine: a chloroquine potentiating indole alkaloid with
      unusual stereochemistry.
AB  - The first total synthesis of malagashanine, a chloroquine potentiating indole
      alkaloid, is presented. A highly stereoselective cascade annulation reaction was
      developed to generate the tetracyclic core of the Malagasy alkaloids. This
      chemistry is likely to be broadly applicable to the synthesis of other members of
      this stereochemically unique family of natural products.

PMID- 28451220
TI  - Four-step iron(ii) spin state cascade driven by antagonistic solid state
      interactions.
AB  - A four-stepped cascade of Fe(ii) high spin (HS) to low spin (LS) states is
      demonstrated in a family of 2-D Hofmann materials,
      [Fe3II(saltrz)6(MII(CN)4)3].8(H2O) (MII = Pd (1Pd ), Pt (1Pt ); saltrz = (E)-2
      (((4H-1,2,4-triazol-4-yl)imino)methyl)phenol). Alongside the fully HS and LS
      Fe(ii) states, fractional spin state stabilization occurs at HS/LS values of 5/6,
      2/3, and 1/6. This unconventional spin state periodicity is driven by the
      presence of multiple spin crossover (SCO) active Fe(ii) sites which are in subtly
      distinct environments driven by a network of antagonistic host-host and host
      guest interactions. Alternating long- and short-range magnetostructural ordering
      is achieved over the five distinct spin state ratios HS1.0LS0.0, HS0.833LS0.167,
      HS0.667LS0.333, HS0.167LS0.833, and HS0.0LS1.0 owing to the flexibility of this 2
      D interdigitated lattice topology interconnected by intermolecular interactions.
      A distinct wave-like spin state patterning is structurally evidenced for each
      intermediate phase.

PMID- 28451221
TI  - Indolo[3,2-b]indole-based crystalline hole-transporting material for highly
      efficient perovskite solar cells.
AB  - We have designed and synthesized fluorinated indolo[3,2-b]indole (IDID)
      derivatives as crystalline hole-transporting materials (HTM) for perovskite solar
      cells. The fluorinated IDID backbone enables a tight molecular arrangement
      stacked by strong pi-pi interactions, leading to a higher hole mobility than that
      of the current HTM standard, p,p-spiro-OMeTAD, with a spherical shape and
      amorphous morphology. Moreover, the photoluminescence quenching in a
      perovskite/HTM film is more effective at the interface of the perovskite with
      IDIDF as compared to that of p,p-spiro-OMeTAD. As a consequence, the device
      fabricated using IDIDF shows superior photovoltaic properties compared to that
      using p,p-spiro-OMeTAD, exhibiting an optimal performance of 19%. Thus, this
      remarkable result demonstrates IDID core-based materials as a new class of HTMs
      for highly efficient perovskite solar cells.

PMID- 28451222
TI  - Porous dendritic copper: an electrocatalyst for highly selective CO2 reduction to
      formate in water/ionic liquid electrolyte.
AB  - Copper is currently extensively studied because it provides promising electrodes
      for carbon dioxide electroreduction. The original combination, reported here, of
      a nanostructured porous dendritic Cu-based material, characterized by electron
      microcopy (SEM, TEM) and X-ray diffraction methods, and a water/ionic liquid
      mixture as the solvent, contributing to CO2 solubilization and activation,
      results in a remarkably efficient (large current densities at low
      overpotentials), stable and selective (large faradic yields) electrocatalytic
      system for the conversion of CO2 into formic acid, a product with a variety of
      uses. These results provide new directions for the further improvement of Cu
      electrodes.

PMID- 28451223
TI  - Imaging specific newly synthesized proteins within cells by fluorescence
      resonance energy transfer.
AB  - Metabolic azide amino acid labelling followed by the use of bioorthogonal
      chemistry is an efficient technique for imaging newly synthesized proteins.
      Recently, AHA-labelling together with the proximity-ligation assay was used to
      identify newly synthesized proteins of interest (POI) (Tom Dieck et al., Nat.
      Meth. 2015, 12, 411). Here we build on this study replacing the proximity
      ligation assay with FRET to improve the spatial resolution. Herein, we develop a
      FRET-based strategy for imaging the newly synthesized endogenous POI within
      cells: a FRET acceptor is installed onto the newly synthesized proteins via click
      chemistry, and a FRET donor onto the POI via immunocytochemistry. We found that a
      photobleaching based FRET efficiency imaging mode and a fluorescence lifetime
      imaging mode showed the distribution of newly synthesized proteins more
      accurately compared to the direct observation of FRET signals. We demonstrated
      the capability of this FRET-based imaging method by visualizing several newly
      synthesized proteins including TDP-43, tubulin and CaMKIIalpha in different cell
      lines. This novel analytical imaging method could be used to visualize other
      specific endogenous proteins of interest in situ.

PMID- 28451224
TI  - Spontaneous mirror symmetry breaking in heterocatalytically coupled
      enantioselective replicators.
AB  - Chiral hypercycle replicators (first-order autocatalysis together with mutual
      cross-catalysis) formed from achiral or racemizing resources may lead to
      spontaneous mirror symmetry breaking (SMSB) without the need for additional
      heterochiral inhibition reactions, such as those of the Frank-like models, which
      are an obstacle for the emergence of evolutionary selection properties. The
      results indicate that the chemical models for the emergence of primordial
      autocatalytic self-reproducing systems, of and by themselves, can also explain
      naturally the emergence of biological homochirality.

PMID- 28451225
TI  - Ru-catalyzed sequence for the synthesis of cyclic amido-ethers.
AB  - Efficient synthesis of versatile building blocks for enabling medicinal chemistry
      research has always challenged synthetic chemists to develop innovative methods.
      Of particular interest are the methods that are amenable to the synthesis of
      chemically distinct and diverse classes of pharmaceutically relevant motifs.
      Herein we report a general method for the one-pot synthesis of cyclic alpha-amido
      ethers containing different amide functionalities including lactams, tetramic
      acids and amino acids. For the incorporation of the nucleotide bases, a chemo and
      regioselective palladium-catalyzed transformation has been developed, providing
      rapid access to nucleoside analogs.

PMID- 28451226
TI  - Engineering catalytic coordination space in a chemically stable Ir-porphyrin MOF
      with a confinement effect inverting conventional Si-H insertion chemoselectivity.
AB  - An iridium-porphyrin ligand, Ir(TCPP)Cl (TCPP = tetrakis(4
      carboxyphenyl)porphyrin), has been utilized to react with HfCl4 to generate a
      stable Ir(iii)-porphyrin metal-organic framework of the formula [(Hf6(MU3
      O)8(OH)2(H2O)10)2(Ir(TCPP)Cl)3].solvents (Ir-PMOF-1(Hf)), which possesses two
      types of open cavities (1.9 * 1.9 * 1.9 and 3.0 * 3.0 * 3.0 nm3) crosslinked
      through orthogonal channels (1.9 * 1.9 nm2) in three directions. The smaller
      cavity is surrounded by four catalytic Ir(TCPP)Cl walls to form a confined
      coordination space as a molecular nanoreactor, while the larger one facilitates
      reactant/product feeding and release. Therefore, the porous Ir-PMOF-1(Hf) can act
      as a multi-channel crystalline molecular flask to promote the carbenoid insertion
      reaction into Si-H bonds, featuring high chemoselectivity towards primary silanes
      among primary, secondary and tertiary silanes under heterogeneous conditions that
      are inaccessible by conventional homogeneous catalysts.

PMID- 28451227
TI  - Covalent triazine framework supported non-noble metal nanoparticles with superior
      activity for catalytic hydrolysis of ammonia borane: from mechanistic study to
      catalyst design.
AB  - Development of non-noble metal catalysts with similar activity and stability to
      noble metals is of significant importance in the conversion and utilization of
      clean energy. The catalytic hydrolysis of ammonia borane (AB) to produce 3 equiv.
      of H2, as an example of where noble metal catalysts significantly outperform
      their non-noble peers, serves as an excellent test site for the design and
      optimization of non-noble metal catalysts. Our kinetic isotopic effect
      measurements reveal, for the first time, that the kinetic key step of the
      hydrolysis is the activation of H2O. Deducibly, a transition metal with an
      optimal electronic structure that bonds H2O and -OH in intermediate strengths
      would favor the hydrolysis of AB. By employing a covalent triazine framework
      (CTF), a newly developed porous material capable of donating electrons through
      the lone pairs on N, the electron densities of nano-sized Co and Ni supported on
      CTF are markedly increased, as well as their catalytic activities. Specifically,
      Co/CTF exhibits a total turnover frequency of 42.3 molH2 molCo-1 min-1 at room
      temperature, which is superior to all peer non-noble metal catalysts ever
      reported and even comparable to some noble metal catalysts.

PMID- 28451229
TI  - Epitaxial growth of unusual 4H hexagonal Ir, Rh, Os, Ru and Cu nanostructures on
      4H Au nanoribbons.
AB  - Metal nanomaterials normally adopt the same crystal structure as their bulk
      counterparts. Herein, for the first time, the unusual 4H hexagonal Ir, Rh, Os, Ru
      and Cu nanostructures have been synthesized on 4H Au nanoribbons (NRBs) via
      solution-phase epitaxial growth under ambient conditions. Interestingly, the 4H
      Au NRBs undergo partial phase transformation from 4H to face-centered cubic (fcc)
      structures after the metal coating. As a result, a series of polytypic 4H/fcc
      bimetallic Au@M (M = Ir, Rh, Os, Ru and Cu) core-shell NRBs has been obtained. We
      believe that the rational crystal structure-controlled synthesis of metal
      nanomaterials will bring new opportunities for exploring their phase-dependent
      physicochemical properties and promising applications.

PMID- 28451228
TI  - Tailored oxido-vanadium(V) cage complexes for selective sulfoxidation in confined
      spaces.
AB  - Five sets of oxido-vanadium(V) complexes, which include both cages and open
      structures, were prepared and tested in the catalytic oxidation of sulfides. It
      was found that the hemicryptophane complexes, which are simultaneously comprised
      of cyclotriveratrylene (CTV), binaphthol and oxido-vanadium(V) moieties, are the
      most efficient supramolecular catalysts. The specific shape of the confined
      hydrophobic space above the metal center leads to a strong improvement in the
      yield, selectivity and rate of the reaction, compared to the other catalysts
      investigated herein. A remarkable turnover number (TON) of 10 000 was obtained,
      which can be attributed to both the high reactivity and stability of the
      catalyst. Similarly to enzymes, the kinetic analysis shows that the mechanism of
      oxidation with the supramolecular catalysts obeys the Michaelis-Menten model, in
      which initial rate saturation occurs upon an increase in substrate concentration.
      This enzyme-like behavior is also supported by the competitive inhibition and
      substrate size-selectivity observed, which underline the crucial role played by
      the cavity.

PMID- 28451230
TI  - Stable alpha/delta phase junction of formamidinium lead iodide perovskites for
      enhanced near-infrared emission.
AB  - Although formamidinium lead iodide (FAPbI3) perovskite has shown great promise in
      the field of perovskite-based optoelectronic devices, it suffers the
      complications of a structural phase transition from a black perovskite phase
      (alpha-FAPbI3) to a yellow non-perovskite phase (delta-FAPbI3). Generally, it is
      pivotal to avoid delta-FAPbI3 since only alpha-FAPbI3 is desirable for
      photoelectric conversion and near-infrared (NIR) emission. However, herein, we
      firstly exploited the undesirable delta-FAPbI3 to enable structurally stable,
      pure FAPbI3 films with a controllable alpha/delta phase junction at low annealing
      temperature (60  degrees C) through stoichiometrically modified precursors
      (FAI/PbI2 = 1.1-1.5). The alpha/delta phase junction contributes to a striking
      stabilization of the perovskite phase of FAPbI3 at low temperature and
      significantly enhanced NIR emission at 780 nm, which is markedly different from
      pure alpha-FAPbI3 (815 nm). In particular, the optimal alpha/delta phase junction
      with FAI/PbI2 = 1.2 exhibited preferable long-term stability against humidity and
      high PLQY of 6.9%, nearly 10-fold higher than that of pure alpha-FAPbI3 (0.7%).
      The present study opens a new approach to realize highly stable and efficient
      emitting perovskite materials by utilizing the phase junctions.

PMID- 28451231
TI  - NMR-filtered virtual screening leads to non-metal chelating metallo-beta
      lactamase inhibitors.
AB  - There are no clinically useful inhibitors of metallo-beta-lactamases (MBLs),
      which are a growing problem because they hydrolyse almost all beta-lactam
      antibacterials. Inhibition by most reported MBL inhibitors involves zinc ion
      chelation. A structure-based virtual screening approach combined with NMR
      filtering led to the identification of inhibitors of the clinically relevant
      Verona Integron-encoded MBL (VIM)-2. Crystallographic analyses reveal a new mode
      of MBL inhibition involving binding adjacent to the active site zinc ions, but
      which does not involve metal chelation. The results will aid efforts to develop
      new types of clinically useful inhibitors targeting MBLs/MBL-fold metallo-enzymes
      involved in antibacterial and anticancer drug resistance.

PMID- 28451232
TI  - Pyrimidine-based twisted donor-acceptor delayed fluorescence molecules: a new
      universal platform for highly efficient blue electroluminescence.
AB  - Deep-blue emitters that can harvest both singlet and triplet excited states to
      give high electron-to-photon conversion efficiencies are highly desired for
      applications in full-color displays and white lighting devices based on organic
      light-emitting diodes (OLEDs). Thermally activated delayed fluorescence (TADF)
      molecules based on highly twisted donor-acceptor (D-A) configurations are
      promising emitting dopants for the construction of efficient deep-blue OLEDs. In
      this study, a simple and versatile D-A system combining acridan-based donors and
      pyrimidine-based acceptors has been developed as a new platform for high
      efficiency deep-blue TADF emitters. The designed pre-twisted acridan-pyrimidine D
      A molecules exhibit small singlet-triplet energy splitting and high
      photoluminescence quantum yields, functioning as efficient deep-blue TADF
      emitters. The OLEDs utilizing these TADF emitters display bright blue
      electroluminescence with external quantum efficiencies of up to 20.4%, maximum
      current efficiencies of 41.7 cd A-1, maximum power efficiencies of 37.2 lm W-1,
      and color coordinates of (0.16, 0.23). The design strategy featuring such acridan
      pyrimidine D-A motifs can offer great prospects for further developing high
      performance deep-blue TADF emitters and TADF-OLEDs.

PMID- 28451233
TI  - Effect of zinc cations on the kinetics of supramolecular assembly and the
      chirality of porphyrin J-aggregates.
AB  - Dilute aqueous solutions of anionic meso-4-sulfonatophenyl-porphyrin (TPPS)
      extract zinc(ii) ions from glass or quartz surfaces at room temperature and
      efficiently form the corresponding metal complex (ZnTPPS). The partial or
      complete formation of ZnTPPS has been probed by UV/Vis spectroscopy and both
      static and time-resolved fluorescence. The source of zinc(ii) ions has been
      clearly identified through inductively coupled plasma optical emission
      spectrometry. The presence of increasing amounts of ZnTPPS slows down the rate of
      TPPS J-aggregate formation in acid solution. This influences the nucleation step
      and has a profound impact on the onset of chirality in these species. This
      evidence indicates the important role of this adventitious metal ion in the
      interpretation of various spectroscopic and kinetic data for the self-assembly of
      the TPPS porphyrin and provides some insights into controversial findings on
      their chirality. The use of this metal derivative as the starting compound for in
      situ formation of monomeric TPPS is suggested.

PMID- 28451234
TI  - A one-dimensional porous carbon-supported Ni/Mo2C dual catalyst for efficient
      water splitting.
AB  - The development of active, stable and low-cost electrocatalysts towards both the
      hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) for overall
      water splitting remains a big challenge. Herein, we report a new porous carbon
      supported Ni/Mo2C (Ni/Mo2C-PC) composite catalyst derived by thermal treatment of
      nickel molybdate nanorods coated with polydopamine, which efficiently and
      robustly catalyses the HER and OER with striking kinetic metrics in alkaline
      electrolyte. The catalyst affords low onset potentials of -60 mV for the HER and
      270 mV for the OER, as well as small overpotentials of 179 mV for the HER and 368
      mV for the OER at a current density of 10 mA cm-2. These results compare
      favorably to Mo2C-PC, Ni-PC, and most other documented Ni- and Mo-based
      catalysts. The high activity of Ni/Mo2C-PC is likely due to electron transfer
      from Ni to Mo2C, leading to a higher Ni valence and a lower Mo valence in the
      Ni/Mo2C-PC catalyst, as these are HER and OER active species and thus account for
      the enhanced activity. Remarkably, our home-made alkaline electrolyser, assembled
      with Ni/Mo2C-PC as a bifunctional catalyst, can enable a water-splitting current
      density of 10 mA cm-2 to be achieved at a low cell voltage of 1.66 V.

PMID- 28451235
TI  - Welcoming natural isotopic abundance in solid-state NMR: probing pi-stacking and
      supramolecular structure of organic nanoassemblies using DNP.
AB  - The self-assembly of small organic molecules is an intriguing phenomenon, which
      provides nanoscale structures for applications in numerous fields from medicine
      to molecular electronics. Detailed knowledge of their structure, in particular on
      the supramolecular level, is a prerequisite for the rational design of improved
      self-assembled systems. In this work, we prove the feasibility of a novel concept
      of NMR-based 3D structure determination of such assemblies in the solid state.
      The key point of this concept is the deliberate use of samples that contain 13C
      at its natural isotopic abundance (NA, 1.1%), while exploiting magic-angle
      spinning dynamic nuclear polarization (MAS-DNP) to compensate for the reduced
      sensitivity. Since dipolar truncation effects are suppressed to a large extent in
      NA samples, unique and highly informative spectra can be recorded which are
      impossible to obtain on an isotopically labeled system. On the self-assembled
      cyclic diphenylalanine peptide, we demonstrate the detection of long-range
      internuclear distances up to ~7 A, allowing us to observe pi-stacking through 13C
      13C correlation spectra, providing a powerful tool for the analysis of one of the
      most important non-covalent interactions. Furthermore, experimental polarization
      transfer curves are in remarkable agreement with numerical simulations based on
      the crystallographic structure, and can be fully rationalized as the
      superposition of intra- and intermolecular contributions. This new approach to
      NMR crystallography provides access to rich and precise structural information,
      opening up a new avenue to de novo crystal structure determination by NMR.

PMID- 28451236
TI  - Cu-Catalyzed aromatic C-H imidation with N-fluorobenzenesulfonimide: mechanistic
      details and predictive models.
AB  - The LCuBr-catalyzed C-H imidation of arenes by N-fluorobenzenesulfonimide (NFSI),
      previously reported by us, utilizes an inexpensive catalyst and is applicable to
      a broad scope of complex arenes. The computational and experimental study
      reported here shows that the mechanism of the reaction is comprised of two parts:
      (1) generation of the active dinuclear CuII-CuII catalyst; and (2) the catalytic
      cycle for the C-H bond imidation of arenes. Computations show that the LCuIBr
      complex used in experiments is not an active catalyst. Instead, upon reacting
      with NFSI it converts to an active dinuclear CuII-CuII catalyst that is detected
      using HRMS techniques. The catalytic cycle starting from the CuII-CuII dinuclear
      complex proceeds via (a) one-electron oxidation of the active catalyst by NFSI to
      generate an imidyl radical and dinuclear CuII-CuIII intermediate, (b) turnover
      limiting single-electron-transfer (SET1) from the arene to the imidyl radical,
      (c) fast C-N bond formation with an imidyl anion and an aryl radical cation, (d)
      reduction of the CuII-CuIII dinuclear intermediate by the aryl radical to
      regenerate the active catalyst and produce an aryl-cation intermediate, and (e)
      deprotonation and rearomatization of the arene ring to form the imidated product.
      The calculated KIE for the turnover-limiting SET1 step reproduces its
      experimentally observed value. A simple predictive tool was developed and
      experimentally validated to determine the regiochemical outcome for a given
      substrate. We demonstrated that the pre-reaction LCuX complexes, where X = Cl, Br
      and I, show a similar reactivity pattern as these complexes convert to the same
      catalytically active dinuclear CuII-CuII species.

PMID- 28451238
TI  - On thermodynamic inconsistencies in several photosynthetic and solar cell models
      and how to fix them.
AB  - We analyze standard theoretical models of solar energy conversion developed to
      study solar cells and photosynthetic systems. We show that assuming the energy
      transfer to the reaction center/electric circuit is through a decay rate or
      "sink", contradicts the second law of thermodynamics. We put forward a
      thermodynamically consistent alternative by explicitly considering parts of the
      reaction center/electric circuit and by employing a Hamiltonian transfer. The
      predicted energy transfer by the new scheme differs from the one found using a
      decay rate, casting doubts on the validity of the conclusions obtained by models
      which include the latter.

PMID- 28451237
TI  - A palladium-catalyzed synthesis of (hetero)aryl-substituted imidazoles from aryl
      halides, imines and carbon monoxide.
AB  - We describe here a tandem catalytic route to prepare imidazoles in a single
      operation from aryl iodides, imines and CO. The reaction involves a catalytic
      carbonylation of aryl halides with imines to form 1,3-dipoles, which undergo
      spontaneous 1,3-dipolar cycloaddition. Overall, this offers an alternative to
      coupling reactions to construct the (hetero)aryl-imidazole motif, where variation
      of the building blocks can allow the synthesis of broad families of imidazoles
      with independent control of all substituents.

PMID- 28451239
TI  - Heptamethylindenyl (Ind*) enables diastereoselective benzamidation of
      cyclopropenes via Rh(iii)-catalyzed C-H activation.
AB  - The diastereoselective coupling of O-substituted arylhydroxamates and
      cyclopropenes mediated by Rh(iii) catalysis was successfully developed. Through
      ligand development, the diastereoselectivity of this reaction was improved using
      a heptamethylindenyl (Ind*) ligand, which has been rationalized using quantum
      chemical calculations. In addition, the nature of the O-substituted ester of
      benzhydroxamic acid proved important for high diastereoselectivity. This
      transformation tolerates a variety of benzamides and cyclopropenes that furnish
      cyclopropa[c]dihydroisoquinolones with high diastereocontrol, which could then be
      easily transformed into synthetically useful building blocks for pharmaceuticals
      and bio-active molecules.

PMID- 28451240
TI  - Ultra-specific discrimination of single-nucleotide mutations using sequestration
      assisted molecular beacons.
AB  - Reliably distinguishing single-nucleotide mutations (SNMs) at low abundance is of
      great significance in clinical diagnosis. However, the specificity of most
      current SNM discrimination methods based on the Watson-Crick hybridization is
      seriously limited by the cross-reactivity of the probe with closely related
      unintended sequences. Herein, we propose a sequestration-assisted molecular
      beacon (MB) strategy for highly specific SNM discrimination. The new SNM
      discrimination system consists of a target-specific MB and a series of hairpin
      sequestering agents (SEQs). The rationally designed hairpin SEQs can effectively
      sequester the corresponding unintended sequences and thus dramatically improve
      the hybridization specificity of the MB in recognizing SNMs. The developed SNM
      discrimination method shows remarkably high specificity (discrimination factors
      ranging from 12 to 1144 with a median of 117) against 20 model SNMs, and can work
      rapidly and robustly over a wide range of conditions. Notably, our SNM
      discrimination method can be easily combined with PCR amplification for the
      detection of KRAS G12D (c.35G>A) and G12V (c.35G>T) mutations at abundance as low
      as 0.5%. This work expands the rule set of designing hybridization-based SNM
      discrimination strategies and shows promising potential application in clinical
      diagnosis.

PMID- 28451241
TI  - Design of multi-functional 2D open-shell organic networks with mechanically
      controllable properties.
AB  - Triarylmethyls (TAMs) are prominent highly attractive open shell organic
      molecular building blocks for materials science, having been used in breakthrough
      syntheses of organic magnetic polymers and metal organic frameworks. With their
      radical pi-conjugated nature and a proven capacity to possess high stability via
      suitable chemical design, TAMs display a variety of desirable characteristics
      which can be exploited for a wide range of applications. Due to their particular
      molecular and electronic structure, the spin localization in TAMs almost entirely
      depends on the dihedral angles of their three aryl rings with respect to the
      central methyl carbon atom plane, which opens up the possibility of controlling
      their fundamental properties by twisting the three aryl rings. Aryl ring twist
      angles can be tuned to a single value by specific chemical functionalisation but
      controlling them by external means in organic materials or devices represents a
      challenging task which has not yet been experimentally achieved. Herein, through
      rational chemical design we propose two 2D covalent organic frameworks (2D-COFs)
      based on specific TAM building blocks. By employing ab initio computational
      modeling we demonstrate that it is possible to externally manipulate the aryl
      ring twist angles in these 2D-linked TAM frameworks by external mechanical means.
      Furthermore, we show this structural manipulation allows for finely tuning the
      most important characteristics of these materials such as spin localization,
      optical electronic transitions and magnetic interactions. Due to the enormous
      technological potential offered by this new class of material and the fact that
      our work is guided by real advances in organic materials synthesis, we believe
      that our predictions will inspire the experimental realization of radical-2D-COFs
      with externally controllable characteristics.

PMID- 28451242
TI  - Steric ploy for alternating donor-acceptor co-assembly and cooperative
      supramolecular polymerization.
AB  - The presence of a bulky peripheral wedge destabilizes the homo-assembly of an
      amide functionalized acceptor (A) monomer and thereby enables the formation of an
      alternating supramolecular copolymer with an amide appended donor (D) monomer via
      the synergistic effect of H-bonding and the charge-transfer (CT) interaction with
      a remarkably high Ka of 31 000 M-1. In sharp contrast, H-bonding driven homo
      polymers of A and D are formed by just replacing the bulky chains of the A
      monomer with linear hydrocarbons. By taking advantage of the clear difference in
      the critical temperature for the onset of the AA or DD homo-assemblies and DA co
      assembly (TDA ? TAA or TDD), the supramolecular polymerization pathway of the NDI
      monomer could be fully diverted from isodesmic to cooperative in the presence of
      a small amount of DAN which helped the in situ production of nucleating sites
      involving the D-A CT-complex at a relatively higher temperature and the
      subsequent chain growth at TAA following the nucleation-elongation model.

PMID- 28451243
TI  - Mild and selective base-free C-H arylation of heteroarenes: experiment and
      computation.
AB  - A mild and selective C-H arylation strategy for indoles, benzofurans and
      benzothiophenes is described. The arylation method engages aryldiazonium salts as
      arylating reagents in equimolar amounts. The protocol is operationally simple,
      base free, moisture tolerant and air tolerant. It utilizes low palladium loadings
      (0.5 to 2.0 mol% Pd), short reaction times, green solvents (EtOAc/2-MeTHF or
      MeOH) and is carried out at room temperature, providing a broad substrate scope
      (47 examples) and excellent selectivity (C-2 arylation for indoles and
      benzofurans, C-3 arylation for benzothiophenes). Mechanistic experiments and DFT
      calculations support a Heck-Matsuda type coupling mechanism.

PMID- 28451244
TI  - Fluorinative ring-opening of cyclopropanes by hypervalent iodine reagents. An
      efficient method for 1,3-oxyfluorination and 1,3-difluorination.
AB  - A new method is presented for 1,3-difluorination and 1,3-oxyfluorination
      reactions. The process is based on iodonium mediated opening of 1,1-disubstituted
      cyclopropanes. The reaction proceeds with high chemo- and regioselectivity under
      mild reaction conditions typically at room temperature in a couple of hours. The
      reaction probably occurs via electrophilic ring-opening of cyclopropanes.

PMID- 28451245
TI  - Protecting microRNAs from RNase degradation with steric DNA nanostructures.
AB  - Tumor suppressive microRNAs are potent molecules that might cure cancer, one day.
      Despite the many advanced strategies for delivery of these microRNAs to the cell,
      there are few therapeutic microRNAs in clinical use. Progress in microRNA
      bioapplications is hindered by a high vulnerability of exogeneous microRNA
      molecules to RNase degradation that occurs in extra- and intracellular
      physiological conditions. In this proof-of-concept study, we use a programmable
      self-assembled DNA nanostructure bearing a "shuriken" shape to not only deliver
      but more importantly protect a tumor suppressive microRNA-145 for a sufficiently
      long time to exert its therapeutic effect in human colorectal cancer cells. Our
      DNA nanostructure harbored complementary sequences that can hybridize with the
      microRNA cargo. This brings the microRNA-DNA duplex very close to the core
      structure such that the microRNA cargo becomes sterically shielded from RNase's
      degradative activity. Our novel DNA nanostructure based protector concept removes
      the degradative bottleneck that may plague other nucleic acid delivery strategies
      and presents a new paradigm towards exploiting these microRNAs for anti-cancer
      therapy.

PMID- 28451246
TI  - Versatile synthesis and enlargement of functionalized distorted heptagon
      containing nanographenes.
AB  - Highly distorted polycyclic aromatic hydrocarbons (PAHs) are predicted to be
      attractive goals in nanoscience owing to the new properties they can exhibit. We
      have shown that a variety of functionalized distorted heptagon-containing
      nanographenes can be easily prepared from simple building blocks by a sequence of
      Co-catalyzed cyclotrimerization and cyclodehydrogenation reactions. The
      versatility of this strategy allows easy subsequent enlargement of these
      nanostructures by Ni-catalyzed cross-coupling and final cyclodehydrogenation
      reactions. Soluble extended distorted nanographenes 1 and 2 containing heptagon
      and an edge-shared pentagon-heptagon combination have been synthesized. High
      distortion of the polycyclic backbone of 2 caused by non-hexagonal rings and a
      helicene moiety was confirmed by X-ray crystallography. Experimental data reveal
      promising optical and electronic properties for distorted PAHs with long
      fluorescence lifetimes (up to 14.5 ns) and low band gaps (down to 2.27 eV). This
      straightforward and versatile synthetic strategy, the observed long fluorescence
      lifetimes and the small optical and electrochemical band gaps for the presented
      compounds may promote the future implementation of distorted graphene molecules
      in electronic devices.

PMID- 28451247
TI  - Cu(0), O2 and mechanical forces: a saving combination for efficient production of
      Cu-NHC complexes.
AB  - Mechanical forces induced by ball-milling agitation enabled the highly efficient
      and widely applicable synthesis of Cu-carbene complexes from N,N-diaryl
      imidazolium salts and metallic copper. The required amount of gaseous dioxygen
      and insoluble copper could be reduced down to stoichiometric quantities, while
      reaction rates clearly outperformed those obtained in solution. Utilisation of
      Cu(0) as the copper source enabled the application of this approach to a wide
      array of N,N-diaryl-imidazolium salts (Cl-, BF4- and PF6-) that transferred their
      counter anion directly to the organometallic complexes. Cu-NHC complexes could be
      produced in excellent yields, including utilisation of highly challenging
      substrates. In addition, five unprecedented organometallic complexes are
      reported.

PMID- 28451248
TI  - Single-atom catalysts for CO2 electroreduction with significant activity and
      selectivity improvements.
AB  - A single-atom catalyst (SAC) has an electronic structure that is very different
      from its bulk counterparts, and has shown an unexpectedly high specific activity
      with a significant reduction in noble metal usage for CO oxidation, fuel cell and
      hydrogen evolution applications, although physical origins of such performance
      enhancements are still poorly understood. Herein, by means of density functional
      theory (DFT) calculations, we for the first time investigate the great potential
      of single atom catalysts for CO2 electroreduction applications. In particular, we
      study a single transition metal atom anchored on defective graphene with single
      or double vacancies, denoted M@sv-Gr or M@dv-Gr, where M = Ag, Au, Co, Cu, Fe,
      Ir, Ni, Os, Pd, Pt, Rh or Ru, as a CO2 reduction catalyst. Many SACs are indeed
      shown to be highly selective for the CO2 reduction reaction over a competitive H2
      evolution reaction due to favorable adsorption of carboxyl (*COOH) or formate
      (*OCHO) over hydrogen (*H) on the catalysts. On the basis of free energy
      profiles, we identified several promising candidate materials for different
      products; Ni@dv-Gr (limiting potential UL = -0.41 V) and Pt@dv-Gr (-0.27 V) for
      CH3OH production, and Os@dv-Gr (-0.52 V) and Ru@dv-Gr (-0.52 V) for CH4
      production. In particular, the Pt@dv-Gr catalyst shows remarkable reduction in
      the limiting potential for CH3OH production compared to any existing catalysts,
      synthesized or predicted. To understand the origin of the activity enhancement of
      SACs, we find that the lack of an atomic ensemble for adsorbate binding and the
      unique electronic structure of the single atom catalysts as well as orbital
      interaction play an important role, contributing to binding energies of SACs that
      deviate considerably from the conventional scaling relation of bulk transition
      metals.

PMID- 28451249
TI  - Geminal bis-borane formation by borane Lewis acid induced cyclopropyl
      rearrangement and its frustrated Lewis pair reaction with carbon dioxide.
AB  - Cyclopropylacetylene reacts with two molar equivalents of Piers' borane
      [HB(C6F5)2] under mild conditions by an addition/rearrangement sequence with
      cyclopropyl ring opening to give a mixture of two alpha-B(C6F5)2 substituted
      tetrahydroboroles. This compound forms an active frustrated Lewis pair with P t
      Bu3 that heterolytically splits dihydrogen and adds carbon dioxide as a geminal
      chelate bis-boryl component. The respective reactions of the two-fold HB(C6F5)2
      addition to Ph-CH2CH2C 0000000000000000000000000000000000
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      0000000000000000000000000000000000 CH were studied as a geminal Lewis acid
      reference. Most of the products were characterized by X-ray diffraction.

PMID- 28451251
TI  - Substrate selectivity of an isolated enoyl reductase catalytic domain from an
      iterative highly reducing fungal polyketide synthase reveals key components of
      programming.
AB  - A cis-acting enoyl reductase (ER) catalytic domain was isolated from a fungal
      highly reducing iterative polyketide synthase (HR-iPKS) for the first time and
      studied in vitro. The ER from the squalestatin tetraketide synthase forms a
      discrete dimeric protein in solution. The ER shows broad substrate selectivity,
      reducing enoyl species including both natural and unnatural substrates.
      Pantetheine-bound substrate thiolesters reacted much faster than the
      corresponding SNAC thiolesters. The unnatural substrates included Z-olefins, 2
      ethyl olefins and pentaketides. Methylation of the substrate modifies the
      activity of the ER such that the 2,4-dimethyl oct-2-enoyl substrate fits into the
      active site but cannot be reduced. A new NMR-based assay was developed for the
      direct observation of the stereochemical preferences at the 4' position of the
      NADPH cofactor and the C-2 and C-3 positions of the substrates. The assay reveals
      that the fungal iPKS ER-catalysed reaction is stereochemically identical to that
      of the vertebrate FAS (vFAS) at the cofactor 4' position and the substrate 3
      position, but the high stereoselectivity displayed by intact SQTKS is lost such
      that reprotonation at the 2-position is unselective by the isolated ER. A 3D
      model of ER was consistent with these observations and showed that the ER may
      sequester its final substrate to prevent further chain extension. The results
      support a developing model for programming by HR-iPKS in which competition for
      substrates between restrictive and permissive catalytic domains chaperones the
      growing polyketide to completion, while allowing for errors and evolution.

PMID- 28451250
TI  - Engineering monolayer poration for rapid exfoliation of microbial membranes.
AB  - The spread of bacterial resistance to traditional antibiotics continues to
      stimulate the search for alternative antimicrobial strategies. All forms of life,
      from bacteria to humans, are postulated to rely on a fundamental host defense
      mechanism, which exploits the formation of open pores in microbial phospholipid
      bilayers. Here we predict that transmembrane poration is not necessary for
      antimicrobial activity and reveal a distinct poration mechanism that targets the
      outer leaflet of phospholipid bilayers. Using a combination of molecular-scale
      and real-time imaging, spectroscopy and spectrometry approaches, we introduce a
      structural motif with a universal insertion mode in reconstituted membranes and
      live bacteria. We demonstrate that this motif rapidly assembles into monolayer
      pits that coalesce during progressive membrane exfoliation, leading to bacterial
      cell death within minutes. The findings offer a new physical basis for designing
      effective antibiotics.

PMID- 28451252
TI  - Label-free target identification using in-gel fluorescence difference via thermal
      stability shift.
AB  - Target engagement is a prerequisite for the therapeutic effects of bioactive
      small molecules, and unbiased identification of their target proteins can
      facilitate drug discovery and chemical biology research. Structural modifications
      of bioactive natural products for target identification exhibit potential
      limitations such as synthetic difficulties, limited supplies from natural
      sources, and loss of original efficacy. Herein, we developed a label-free method
      for proteome-wide target identification using in-gel fluorescence difference
      caused by thermal stability shift, namely TS-FITGE. Quantitative intra-gel image
      analysis of each protein spot revealed target proteins with shifted thermal
      stability upon drug engagement, and plotting of melting curves by inter-gel
      analysis confirmed the positive targets. We demonstrated the robustness and
      applicability of the TS-FITGE method by identifying target proteins, including
      membrane-anchored proteins, of complex bioactive compounds. Furthermore, we
      identified and functionally validated nucleophosmin as a novel target protein of
      hordenine, a natural product upregulator of in vitro translation.

PMID- 28451253
TI  - Reversible ratiometric detection of highly reactive hydropersulfides using a FRET
      based dual emission fluorescent probe.
AB  - Hydropersulfide (R-SSH) is an important class of reactive sulfur species (RSS)
      involved in a variety of physiological processes in mammals. A fluorescent probe
      capable of real-time detection of hydropersulfide levels in living cells would be
      a versatile tool to elucidate its roles in cell signalling and redox homeostasis.
      In this paper, we report a ratiometric fluorescent probe for hydropersulfide
      sensing, based on a fluorescence resonance energy transfer (FRET) mechanism. This
      sensing mechanism involves a nucleophilic reaction of a hydropersulfide with the
      pyronine-unit of the probe, which modulates the intramolecular FRET efficiency to
      induce a dual-emission change. The reversible nature of this reaction allows us
      to detect increases and decreases of hydropersulfide levels in a real-time
      manner. The probe fluorometrically sensed highly reactive hydropersulfides, such
      as H2S2 and Cys-SSH, while the fluorescence response to biologically abundant
      cysteine and glutathione was negligible. Taking advantage of the reversible and
      selective sensing properties, this probe was successfully applied to the
      ratiometric imaging of concentration dynamics of endogenously produced
      hydropersulfides in living cells.

PMID- 28451254
TI  - Fluorogenic protein labeling using a genetically encoded unstrained alkene.
AB  - We developed a new fluorogenic bioorthogonal reaction that is based on the
      inverse electron-demand Diels-Alder reaction between styrene (an unstrained
      alkene) and a simple tetrazine. The reaction forms a new fluorophore with no
      literature precedent. We have identified an aminoacyl-tRNA synthetase/tRNA pair
      for the efficient and site-specific incorporation of a styrene-containing amino
      acid into proteins in response to amber nonsense codon. Fluorogenic labeling of
      purified proteins and intact proteins in live cells were demonstrated. The
      fluorogenicity of the styrene-tetrazine reaction can be potentially applied to
      the study of protein folding and function under physiological conditions with low
      background fluorescence interference.

PMID- 28451255
TI  - Charge delocalization characteristics of regioregular high mobility polymers.
AB  - Controlling the regioregularity among the structural units of narrow bandgap
      conjugated polymer backbones has led to improvements in optoelectronic
      properties, for example in the mobilities observed in field effect transistor
      devices. To investigate how the regioregularity affects quantities relevant to
      hole transport, regioregular and regiorandom oligomers representative of
      polymeric structures were studied using density functional theory. Several
      structural and electronic characteristics of the oligomers were compared,
      including chain planarity, cation spin density, excess charges on molecular units
      and internal reorganizational energy. The main difference between the
      regioregular and regiorandom oligomers is found to be the conjugated backbone
      planarity, while the reorganizational energies calculated are quite similar
      across the molecular family. This work constitutes the first step on
      understanding the complex interplay of atomistic changes and an oligomer backbone
      structure toward modeling the charge transport properties.

PMID- 28451256
TI  - LC-MS/MS suggests that hole hopping in cytochrome c peroxidase protects its heme
      from oxidative modification by excess H2O2.
AB  - We recently reported that cytochrome c peroxidase (Ccp1) functions as a H2O2
      sensor protein when H2O2 levels rise in respiring yeast. The availability of its
      reducing substrate, ferrocytochrome c (CycII), determines whether Ccp1 acts as a
      H2O2 sensor or peroxidase. For H2O2 to serve as a signal it must modify its
      receptor so we employed high-performance LC-MS/MS to investigate in detail the
      oxidation of Ccp1 by 1, 5 and 10 M eq. of H2O2 in the absence of CycII to prevent
      peroxidase activity. We observe strictly heme-mediated oxidation, implicating
      sequential cycles of binding and reduction of H2O2 at Ccp1's heme. This results
      in the incorporation of ~20 oxygen atoms predominantly at methionine and
      tryptophan residues. Extensive intramolecular dityrosine crosslinking involving
      neighboring residues was uncovered by LC-MS/MS sequencing of the crosslinked
      peptides. The proximal heme ligand, H175, is converted to oxo-histidine, which
      labilizes the heme but irreversible heme oxidation is avoided by hole hopping to
      the polypeptide until oxidation of the catalytic distal H52 in Ccp1 treated with
      10 M eq. of H2O2 shuts down heterolytic cleavage of H2O2 at the heme. Mapping of
      the 24 oxidized residues in Ccp1 reveals that hole hopping from the heme is
      directed to three polypeptide zones rich in redox-active residues. This
      unprecedented analysis unveils the remarkable capacity of a polypeptide to direct
      hole hopping away from its active site, consistent with heme labilization being a
      key outcome of Ccp1-mediated H2O2 signaling. LC-MS/MS identification of the
      oxidized residues also exposes the bias of electron paramagnetic resonance (EPR)
      detection toward transient radicals with low O2 reactivity.

PMID- 28451257
TI  - Butane-1,2,3,4-tetraol-based amphiphilic stereoisomers for membrane protein
      study: importance of chirality in the linker region.
AB  - Amphiphile selection is a crucial step in membrane protein structural and
      functional study. As conventional detergents have limited scope and utility,
      novel agents with enhanced efficacy need to be developed. Although a large number
      of novel agents have been reported, so far there has been no systematically
      designed comparative study of the protein stabilization efficacy of stereo
      isomeric amphiphiles. Here we designed and prepared a novel class of stereo
      isomeric amphiphiles, designated butane-1,2,3,4-tetraol-based maltosides (BTMs).
      These stereoisomers showed markedly different behaviour for most of the targeted
      membrane proteins depending on the chirality of the linker region. These findings
      indicate an important role for detergent stereochemistry in membrane protein
      stabilization. In addition, we generally observed enhanced detergent efficacy
      with increasing alkyl chain length, reinforcing the importance of the balance
      between hydrophobicity and hydrophilicity in detergent design. The stereo
      isomeric difference in detergent efficacy observed provides an important design
      principle for the development of novel amphiphiles for membrane protein
      manipulation.

PMID- 28451258
TI  - Exchange-bias quantum tunnelling in a CO2-based Dy4-single molecule magnet.
AB  - Carbamate formation in green-plants through the RuBisCO enzyme continuously plays
      a pivotal role in the conversion of CO2 from the atmosphere into biomass. With
      this in mind, carbamate formation from CO2 by a lanthanide source in the presence
      of a secondary amine is herein explored leading to a lanthanide-carbamate cage
      with the formula [Dy4(O2CNiPr2)12]. Magnetic studies show slow relaxation leading
      to the observation of hysteresis loops; the tetranuclear cage being a single
      molecule magnet. Detailed interpretation of the data reveals: (i) the presence of
      two different exchange interactions, ferromagnetic and antiferromagnetic and (ii)
      the observation of exchange-bias quantum tunnelling with two distinct sets of
      loops, attributable to ferromagnetic interactions between dysprosium ions at
      longer distances and antiferromagnetic exchange between dysprosium ions at
      shorter distances. The results clearly demonstrate that the [Dy4(O2CNiPr2)12]
      cage acts as a quantum magnet which in turn could be at the heart of hybrid
      spintronic devices after having implemented CO2 as a feedstock.

PMID- 28451259
TI  - Hydrogen-adduction to open-shell graphene fragments: spectroscopy,
      thermochemistry and astrochemistry.
AB  - We apply a combination of state-of-the-art experimental and quantum-chemical
      methods to elucidate the electronic and chemical energetics of hydrogen adduction
      to a model open-shell graphene fragment. The lowest-energy adduct, 1H-phenalene,
      is determined to have a bond dissociation energy of 258.1 kJ mol-1, while other
      isomers exhibit reduced or in some cases negative bond dissociation energies, the
      metastable species being bound by the emergence of a conical intersection along
      the high-symmetry dissociation coordinate. The gas-phase excitation spectrum of
      1H-phenalene and its radical cation are recorded using laser spectroscopy coupled
      to mass-spectrometry. Several electronically excited states of both species are
      observed, allowing the determination of the excited-state bond dissociation
      energy. The ionization energy of 1H-phenalene is determined to be 7.449(17) eV,
      consistent with high-level W1X-2 calculations.

PMID- 28451260
TI  - The dual role of thiourea in the thiotrifluoromethylation of alkenes.
AB  - Alkenes substituted with a thiourea undergo C-CF3 followed by intramolecular C-S
      bond formation with the Togni reagent and trifluoroacetic acid (TFA) at room
      temperature; thiols and thioamides are not suitable S-sources for this reaction.
      This anti-addition process involves a CF3 radical, and affords CF3-substituted
      thiazolines and thiazines for medicinal applications. A metal or photoredox
      catalyst is not required as the thiourea acts as a reductant, as well as serving
      as an S-source capable of adding to a C-centered radical. Mechanistic work
      comparing the reactivity of thiourea, urea, thioamide and thiol in the context of
      alkene trifluoromethylation demonstrates that in this series, the thiourea is
      unique for its ability to release CF3 radical from the Togni reagent, and to
      orchestrate trifluoromethylation followed by S-cyclization with both activated
      and unactivated alkenes.

PMID- 28451261
TI  - Low picomolar, instrument-free visual detection of mercury and silver ions using
      low-cost programmable nanoprobes.
AB  - The EPA's recommended maximum allowable level of inorganic mercury in drinking
      water is 2 ppb (10 nM). To our knowledge, the most sensitive colorimetric mercury
      sensor reported to date has a limit of detection (LOD) of 800 pM. Here, we report
      an instrument-free and highly practical colorimetric methodology, which enables
      detection of as low as 2 ppt (10 pM) of mercury and/or silver ions with the naked
      eye using a gold nanoprobe. Synthesis of the nanoprobe costs less than $1.42,
      which is enough to perform 200 tests in a microplate; less than a penny for each
      test. We have demonstrated the detection of inorganic mercury from water, soil
      and urine samples. The assay takes about four hours and the color change is
      observed within minutes after the addition of the last required element of the
      assay. The nanoprobe is highly programmable which allows for the detection of
      mercury and/or silver ions separately or simultaneously by changing only a single
      parameter of the assay. This highly sensitive approach for the visual detection
      relies on the combination of the signal amplification features of the
      hybridization chain reaction with the plasmonic properties of the gold
      nanoparticles. Considering that heavy metal ion contamination of natural
      resources is a major challenge and routine environmental monitoring is needed,
      yet time-consuming, this colorimetric approach may be instrumental for on-site
      heavy metal ion detection. Since the color transition can be measured in a
      variety of formats including using the naked eye, a simple UV-Vis
      spectrophotometer, or recording using mobile phone apps for future directions,
      our cost-efficient assay and method have the potential to be translated into the
      field.

PMID- 28451262
TI  - Molecular titanium nitrides: nucleophiles unleashed.
AB  - In this contribution we present reactivity studies of a rare example of a
      titanium salt, in the form of [MU2-K(OEt2)]2[(PN)2Ti
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      0000000000000000000000000000000000 0000000000000000000000000000000000 N]2 (1) (PN
      = N-(2-(diisopropylphosphino)-4-methylphenyl)-2,4,6-trimethylanilide) to produce
      a series of imide moieties including rare examples such as methylimido,
      borylimido, phosphonylimido, and a parent imido. For the latter, using various
      weak acids allowed us to narrow the pKa range of the NH group in (PN)2TiNH to be
      between 26-36. Complex 1 could be produced by a reductively promoted elimination
      of N2 from the azide precursor (PN)2TiN3, whereas reductive splitting of N2 could
      not be achieved using the complex (PN)2Ti 0000000000000000000000000000000000
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      0000000000000000000000000000000000 NNTi(PN)2 (2) and a strong reductant. Complete
      N-atom transfer reactions could also be observed when 1 was treated with
      ClC(O)tBu and OCCPh2 to form NCtBu and KNCCPh2, respectively, along with the
      terminal oxo complex (PN)2TiO, which was also characterized. A combination of
      solid state 15N NMR (MAS) and theoretical studies allowed us to understand the
      shielding effect of the counter cation in dimer 1, the monomer [K(18-crown
      6)][(PN)2TiN], and the discrete salt [K(2,2,2-Kryptofix)][(PN)2TiN] as well as
      the origin of the highly downfield 15N NMR resonance when shifting from dimer to
      monomer to a terminal nitride (discrete salt). The upfield shift of 15Nnitride
      resonance in the 15N NMR spectrum was found to be linked to the K+ induced
      electronic structural change of the titanium-nitride functionality by using a
      combination of MO analysis and quantum chemical analysis of the corresponding
      shielding tensors.

PMID- 28451263
TI  - Polymorphism at 129 dictates metastable conformations of the human prion protein
      N-terminal beta-sheet.
AB  - We study the thermodynamic stability of the native state of the human prion
      protein using a new free-energy method, replica-exchange on-the-fly
      parameterization. This method is designed to overcome hidden-variable sampling
      limitations to yield nearly error-free free-energy profiles along a
      conformational coordinate. We confirm that all four (M129V, D178N) polymorphs
      have a ground-state conformation with three intact beta-sheet hydrogen bonds.
      Additionally, they are observed to have distinct metastabilities determined by
      the side-chain at position 129. We rationalize these findings with reference to
      the prion "strain" hypothesis, which links the variety of transmissible
      spongiform encephalopathy phenotypes to conformationally distinct infectious
      prion forms and classifies distinct phenotypes of sporadic Creutzfeldt-Jakob
      disease based solely on the 129 polymorphism. Because such metastable structures
      are not easily observed in structural experiments, our approach could potentially
      provide new insights into the conformational origins of prion diseases and other
      pathologies arising from protein misfolding and aggregation.

PMID- 28451264
TI  - One-pot palladium-catalyzed synthesis of sulfonyl fluorides from aryl bromides.
AB  - A mild, efficient synthesis of sulfonyl fluorides from aryl and heteroaryl
      bromides utilizing palladium catalysis is described. The process involves the
      initial palladium-catalyzed sulfonylation of aryl bromides using DABSO as an SO2
      source, followed by in situ treatment of the resultant sulfinate with the
      electrophilic fluorine source NFSI. This sequence represents the first general
      method for the sulfonylation of aryl bromides, and offers a practical, one-pot
      alternative to previously described syntheses of sulfonyl fluorides, allowing
      rapid access to these biologically important molecules. Excellent functional
      group tolerance is demonstrated, with the transformation successfully achieved on
      a number of active pharmaceutical ingredients, and their precursors. The
      preparation of peptide-derived sulfonyl fluorides is also demonstrated.

PMID- 28451265
TI  - A new approach to the asymmetric Mannich reaction catalyzed by chiral N,N'
      dioxide-metal complexes.
AB  - A highly efficient asymmetric Mannich-type reaction between alpha-tetralone
      derived beta-keto esters/amides and 1,3,5-triaryl-1,3,5-triazinanes was realized
      in the presence of chiral N,N'-dioxide-Ni(ii) or Mg(ii) complex. A variety of
      optically active beta-amino compounds with all-carbon quaternary stereocenters
      were obtained in good yields with excellent enantioselectivities. A possible
      transition state was proposed based on these experiments and previous reports.

PMID- 28451266
TI  - Plasmon-enhanced Raman spectroscopic metrics for in situ quantitative and dynamic
      assays of cell apoptosis and necrosis.
AB  - Apoptosis and necrosis are distinct cell death processes related to many cellular
      pathways. In situ, quantitatively and dynamically monitoring such processes may
      provide vitally important information for cell studies. However, such a method
      still remains elusive, even though current immunochemical methodologies have
      developed extremely valuable tools. Herein, we demonstrate Raman spectroscopic
      metrics for validating and quantifying apoptotic and necrotic cells based on
      their distinct molecular vibrational fingerprints. It not only allows us to
      quantify apoptotic and necrotic cell populations in situ in adherent cell
      samples, but also to be capable of continuously monitoring the dynamical
      processes of apoptosis and necrosis at the same time in one sample. This method
      provides comparable results with the "gold standard" of flow cytometry, moreover,
      with several incomparable advantages. Our work offers a powerful new tool for
      cell apoptosis and necrosis assays and is expected to become a benchmark
      technology in biological and medical studies.

PMID- 28451267
TI  - Micro-flow photosynthesis of new dienophiles for inverse-electron-demand Diels
      Alder reactions. Potential applications for pretargeted in vivo PET imaging.
AB  - Pretargeted PET imaging has emerged as an effective two-step in vivo approach
      that combines the superior affinity and selectivity of antibodies with the rapid
      pharmacokinetics and favorable dosimetry of smaller molecules radiolabeled with
      short-lived radionuclides. This approach can be based on the bioorthogonal
      inverse-electron-demand Diels-Alder (IEDDA) reaction between tetrazines and trans
      cyclooctene (TCO) derivatives. We aimed to develop new [18F]TCO-dienophiles with
      high reactivity for IEDDA reactions, and favorable in vivo stability and
      pharmacokinetics. New dienophiles were synthesized using an innovative micro-flow
      photochemistry process, and their reaction kinetics with a tetrazine were
      determined. In vivo stability and biodistribution of the most promising 18F
      radiolabeled-TCO-derivative ([18F]3) was investigated, and its potential for in
      vivo pretargeted PET imaging was assessed in tumor-bearing mice. We demonstrated
      that [18F]3 is a suitable dienophile for IEDDA reactions and for pretargeting
      applications.

PMID- 28451268
TI  - Stable green phosphorescence organic light-emitting diodes with low efficiency
      roll-off using a novel bipolar thermally activated delayed fluorescence material
      as host.
AB  - A novel bipolar hosting material, 11-(3-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)
      12,12-dimethyl-11,12-dihydroindeno[2,1-a]carbazole (DPDDC), was designed,
      synthesized, and characterized for green phosphorescent organic light-emitting
      diodes (PhOLEDs). The DPDDC exhibits excellent hole and electron transport
      properties, superior thermal stability, a high glass-transition temperature and a
      small singlet-triplet energy gap for efficient reverse intersystem crossing from
      triplet to singlet, reducing the triplet density of the host for PhOLEDs. The
      electrophosphorescence properties of the devices using DPDDC as the host and
      three green phosphorescent iridium(iii) complexes, bis(2-(4-tolyl)pyridinato
      N,C2')iridium(iii) acetylacetonate, bis(2-phenylpyridine)iridium(iii)
      acetylacetonate, and bis(4-methyl-2,5-diphenylpyridine)iridium(iii)
      acetylacetonate [(mdppy)2Iracac] as the emitter were investigated. The green
      PhOLED with 5 wt% (mdppy)2Iracac presents an excellent performance, including a
      high power efficiency of 92.3 lm W-1, high external quantum efficiency of 23.6%,
      current efficiency roll-off as low as 5.5% at 5000 cd m-2 and a twentyfold
      lifetime improvement (time to 90% of the 5000 cd m-2 initial luminance) over the
      reference electrophosphorescent device.

PMID- 28451270
TI  - Co/NHPI-mediated aerobic oxygenation of benzylic C-H bonds in pharmaceutically
      relevant molecules.
AB  - A simple cobalt(ii)/N-hydroxyphthalimide catalyst system has been identified for
      selective conversion of benzylic methylene groups in pharmaceutically relevant
      (hetero)arenes to the corresponding (hetero)aryl ketones. The radical reaction
      pathway tolerates electronically diverse benzylic C-H bonds, contrasting recent
      oxygenation reactions that are initiated by deprotonation of a benzylic C-H bond.
      The reactions proceed under practical reaction conditions (1 M substrate in BuOAc
      or EtOAc solvent, 12 h, 90-100  degrees C), and they tolerate common
      heterocycles, such as pyridines and imidazoles. A cobalt-free, electrochemical,
      NHPI-catalyzed oxygenation method overcomes challenges encountered with chelating
      substrates that inhibit the chemical reaction. The utility of the aerobic
      oxidation method is showcased in the multigram synthesis of a key intermediate
      towards a drug candidate (AMG 579) under process-relevant reaction conditions.

PMID- 28451269
TI  - Enhancement of the physicochemical properties of [Pt(dien)(nucleobase)]2+ for
      HIVNCp7 targeting.
AB  - Physicochemical properties of coordination compounds can be exploited for
      molecular recognition of biomolecules. The inherent pi-pi stacking properties of
      [Pt(chelate)(N-donor)]2+ ([PtN4]) complexes were modulated by systematic
      variation of the chelate (diethylenetriamine and substituted derivatives) and N
      donor (nucleobase or nucleoside) in the formally substitution-inert PtN4
      coordination sphere. Approaches to target the HIV nucleocapsid protein HIVNCp7
      are summarized building on (i) assessment of stacking interactions with simple
      tryptophan or tryptophan derivatives to (ii) the tryptophan-containing C-terminal
      zinc finger and (iii) to the full two-zinc finger peptide and its interactions
      with RNA and DNA. The xanthosine nucleoside was identified as having
      significantly enhanced stacking capability over guanosine. Correlation of the
      LUMO energies of the modified nucleobases with the DFT pi-stacking energies shows
      that frontier orbital energies of the individual monomers can be used as a first
      estimate of the pi-stacking strength to Trp. Cellular accumulation studies showed
      no significant correlation with lipophilicity of the compounds, but all compounds
      had very low cytotoxicity suggesting the potential for antiviral selectivity. The
      conceptual similarities between nucleobase alkylation and platination validates
      the design of formally substitution-inert coordination complexes as weak Lewis
      acid electrophiles for selective peptide targeting.

PMID- 28451271
TI  - Hydroxide-bridged five-coordinate DyIII single-molecule magnet exhibiting the
      record thermal relaxation barrier of magnetization among lanthanide-only dimers.
AB  - A hydroxide-bridged centrosymmetric DyIII dimer with each DyIII being five
      coordinated has been synthesized using bulky hindered phenolate ligands. Magnetic
      studies revealed that this compound exhibits a slow magnetic relaxation of a
      single-ion origin together with a step-like magnetic hysteresis of the magnetic
      coupled cluster. The thermal relaxation barrier of magnetization is 721 K in the
      absence of a static magnetic field, while the intramolecular magnetic interaction
      is very large among reported 4f-only dimers. CASSCF calculations with a larger
      active space were performed to understand the electronic structure of the
      compound. The thermal relaxation regime and the quantum tunneling regime are well
      separated, representing a good model to study the relaxation mechanism of SMMs
      with intramolecular Dy-Dy magnetic interactions.

PMID- 28451272
TI  - beta-Hairpin mimics containing a piperidine-pyrrolidine scaffold modulate the
      beta-amyloid aggregation process preserving the monomer species.
AB  - Alzheimer's disease is a neurodegenerative disorder linked to oligomerization and
      fibrillization of amyloid beta peptides, with Abeta1-42 being the most
      aggregative and neurotoxic one. We report herein the synthesis and conformational
      analysis of Abeta1-42-amyloid related beta-hairpin peptidomimetics, built on a
      piperidine-pyrrolidine semi rigid beta-turn inducer and bearing two small
      recognition peptide sequences, designed on oligomeric and fibril structures of
      Abeta1-42. According to these peptide sequences, a stable beta-hairpin or a
      dynamic equilibrium between two possible architectures was observed. These
      original constructs are able to greatly delay the kinetics of Abeta1-42
      aggregation process as demonstrated by thioflavin-T fluorescence, and
      transmission electron microscopy. Capillary electrophoresis indicates their
      ability to preserve the monomer species, inhibiting the formation of toxic
      oligomers. Furthermore, compounds protect against toxic effects of Abeta on
      neuroblastoma cells even at substoichiometric concentrations. This study is the
      first example of acyclic small beta-hairpin mimics possessing such a highly
      efficient anti-aggregation activity. The protective effect is more pronounced
      than that observed with molecules which have undergone clinical trials. The
      structural elements made in this study provide valuable insights in the
      understanding of the aggregation process and insights to explore the design of
      novel acyclic beta-hairpin targeting other types of amyloid-forming proteins.

PMID- 28451273
TI  - Electronic nature of zwitterionic alkali metal methanides, silanides and
      germanides - a combined experimental and computational approach.
AB  - Zwitterionic group 14 complexes of the alkali metals of formula
      [C(SiMe2OCH2CH2OMe)3M], (M-1), [Si(SiMe2OCH2CH2OMe)3M], (M-2),
      [Ge(SiMe2OCH2CH2OMe)3M], (M-3), where M = Li, Na or K, have been prepared,
      structurally characterized and their electronic nature was investigated by
      computational methods. Zwitterions M-2 and M-3 were synthesized via reactions of
      [Si(SiMe2OCH2CH2OMe)4] (2) and [Ge(SiMe2OCH2CH2OMe)4] (3) with MOBu t (M = Li, Na
      or K), resp., in almost quantitative yields, while M-1 were prepared from
      deprotonation of [HC(SiMe2OCH2CH2OMe)3] (1) with LiBu t , NaCH2Ph and KCH2Ph,
      resp. X-ray crystallographic studies and DFT calculations in the gas-phase,
      including calculations of the NPA charges confirm the zwitterionic nature of
      these compounds, with the alkali metal cations being rigidly locked and charge
      separated from the anion by the internal OCH2CH2OMe donor groups. Natural bond
      orbital (NBO) analysis and the second order perturbation theory analysis of the
      NBOs reveal significant hyperconjugative interactions in M-1-M-3, primarily
      between the lone pair and the antibonding Si-O orbitals, the extent of which
      decreases in the order M-1 > M-2 > M-3. The experimental basicities and the
      calculated gas-phase basicities of M-1-M-3 reveal the zwitterionic alkali metal
      methanides M-1 to be significantly stronger bases than the analogous silanides M
      2 and germanium M-3.

PMID- 28451274
TI  - A metal-mediated base pair that discriminates between the canonical pyrimidine
      nucleobases.
AB  - A nucleoside analogue comprising the ligand 1H-imidazo[4,5-f][1,10]phenanthroline
      (P) was applied to develop a molecular beacon capable of discriminating the
      canonical nucleobases cytosine and thymine. The beacon is based on the formation
      of a stable Ag+-mediated base pair between P and cytosine, whereas the presence
      of Ag+ strongly destabilizes nucleic acids comprising an artificial base pair
      between P and thymine. Metal-mediated base pair formation was investigated by
      temperature-dependent UV spectroscopy and CD spectroscopy and complemented by
      extensive DFT calculations. The molecular beacon significantly extends the
      application spectrum of nucleic acids with metal-mediated base pairs. It is of
      potential use in the detection of single-nucleotide polymorphisms.

PMID- 28451275
TI  - Palladium(0)-catalyzed asymmetric C(sp3)-H arylation using a chiral binol-derived
      phosphate and an achiral ligand.
AB  - The first efficient palladium(0)-catalyzed enantioselective C(sp3)-H activation
      reaction using a catalytic chiral base and an achiral phosphine ligand is
      reported. Fine-tuning the binol-derived phosphoric acid pre-catalyst and the
      reaction conditions was found to be crucial to achieve high levels of
      enantioselectivity for a variety of indoline products containing both tri- and
      tetrasubstituted stereocenters.

PMID- 28451276
TI  - Integration of aerobic oxidation and intramolecular asymmetric aza-Friedel-Crafts
      reactions with a chiral bifunctional heterogeneous catalyst.
AB  - A new class of chiral bifunctional heterogeneous materials composed of Au/Pd
      nanoparticles and chiral phosphoric acids as active orthogonal catalysts was
      prepared by utilizing a facile pseudo-suspension co-polymerization method. It was
      found that this heterogeneous catalyst was capable of facilitating the sequential
      aerobic oxidation-asymmetric intramolecular aza-Friedel-Crafts reaction between
      benzyl alcohols and N-aminoethylpyrroles. Moreover, the designed chiral
      heterogeneous catalyst could be recovered and reused several times without
      significant loss of activity or enantioselectivity.

PMID- 28451277
TI  - Sulfur rich electron donors - formation of singlet versus triplet radical ion
      pair states featuring different lifetimes in the same conjugate.
AB  - An unprecedented family of novel electron-donor acceptor conjugates based on
      fullerenes as electron acceptors, on one hand, and triphenyl amines as electron
      donors, on the other hand, have been synthesized and characterized in a variety
      of solvents using steady state absorption/emission as well as transient
      absorption spectroscopy. These are unprecedented in terms of their outcome of
      radical ion pair formation, that is, the singlet versus triplet excited state.
      This was corroborated by femto/nanosecond pump probe experiments and by molecular
      orbital calculations. Not only has the donor strength of the triphenylamines been
      systematically altered by appending one or two sulfur rich dithiafulvenes, but
      the presence of the latter changed the nature of the radical ion pair state.
      Importantly, depending on the excitation wavelength, that is, either where the
      fullerenes or where the triphenylamines absorb, short-lived or long-lived radical
      ion pair states, respectively, are formed. The short-lived component with a
      lifetime as short as 6 ps has singlet character and stems from a fullerene
      singlet excited state precursor. In contrast, the long-lived component has a
      lifetime of up to 130 ns in THF, has triplet character, and evolves from a
      triplet excited state precursor. Key in forming more than three orders of
      magnitude longer lived radical ion pair states is the presence of sulfur atoms,
      which enhance spin-orbit coupling and, in turn, intersystem crossing. Independent
      confirmation for the singlet versus triplet character came from temperature
      dependent measurements with a focus on the radical ion pair state lifetimes.
      Here, activation barriers of 2.4 and 10.0 kJ mol-1 for the singlet and triplet
      radical ion pair state, respectively, were established.

PMID- 28451278
TI  - Magnetic circular dichroism studies of iron(ii) binding to human calprotectin.
AB  - Calprotectin (CP) is an abundant metal-chelating protein involved in host
      defense, and the ability of human CP to bind Fe(ii) in a calcium-dependent manner
      was recently discovered. In the present study, near-infrared magnetic circular
      dichroism spectroscopy is employed to investigate the nature of Fe(ii)
      coordination at the two transition-metal-binding sites of CP that are a His3Asp
      motif (site 1) and a His6 motif (site 2). Upon the addition of sub-stoichiometric
      Fe(ii), a six-coordinate (6C) Fe(ii) center associated with site 2 is
      preferentially formed in the presence of excess Ca(ii). This site exhibits an
      exceptionally large ligand field (10Dq = 11 045 cm-1) for a non-heme Fe(ii)
      protein. Analysis of CP variants lacking residues of the His6 motif supports that
      CP coordinates Fe(ii) at site 2 by employing six His ligands. In the presence of
      greater than one equiv. of Fe(ii) or upon mutation of the His6 motif, the metal
      ion also binds at site 1 of CP to form a five-coordinate (5C) Fe(ii)-His3Asp
      motif that was previously unidentified in this system. Notably, the introduction
      of His-to-Ala mutations at the His6 motif results in a mixture of 6C (site 2) and
      5C (site 1) signals in the presence of sub-stoichiometric Fe(ii). These results
      are consistent with a reduced Fe(ii)-binding affinity of site 2 as more weakly
      coordinating water-derived ligands complete the 6C site. In the absence of
      Ca(ii), both sites 1 and 2 are occupied upon addition of sub-stoichiometric
      Fe(ii), and a stronger ligand field is observed for the 5C site. These
      spectroscopic studies provide further evaluation of a unique non-heme Fe(ii)-His6
      site for metalloproteins and support the notion that Ca(ii) ions influence the
      Fe(ii)-binding properties of CP.

PMID- 28451279
TI  - Exploiting directional long range secondary forces for regulating electrostatics
      dominated noncovalent interactions.
AB  - It has been well established that long range secondary electrostatic interactions
      (SEIs) have a significant effect on the stability of supramolecular complexes.
      However, general rules for exploiting SEIs in the rational design of diverse
      supramolecular complexes have been difficult to obtain. In this work, we outline
      a quantum chemical approach for understanding the strength of electrostatic
      interactions. This approach is seen to provide excellent correlation between the
      electrostatic force and the binding energy between two partners in hydrogen
      bonded complexes, as well as that between two ions in ion-pair complexes.
      Furthermore, we illustrate how the understanding of the binding allows for the
      rational design of new complexes where the association constant between the two
      partners can be increased or decreased, as desired, by several orders of
      magnitude. Hence, the current work showcases a general, simple and powerful
      method of understanding and exploiting long range secondary electrostatic
      interactions.

PMID- 28451280
TI  - Nanometer patterning of water by tetraanionic ferrocyanide stabilized in aqueous
      nanodrops.
AB  - Formation of the small, highly charged tetraanion ferrocyanide, Fe(CN)64-,
      stabilized in aqueous nanodrops is reported. Ion-water interactions inside these
      nanodrops are probed using blackbody infrared radiative dissociation, infrared
      photodissociation (IRPD) spectroscopy, and molecular modeling in order to
      determine how water molecules stabilize this highly charged anion and the extent
      to which the tetraanion patterns the hydrogen-bonding network of water at long
      distance. Fe(CN)64-(H2O)38 is the smallest cluster formed directly by
      nanoelectrospray ionization. Ejection of an electron from this ion to form
      Fe(CN)63-(H2O)38 occurs with low-energy activation, but loss of a water molecule
      is favored at higher energy indicating that water molecule loss is entropically
      favored over loss of an electron. The second solvation shell is almost complete
      at this cluster size indicating that nearly two solvent shells are required to
      stabilize this highly charged anion. The extent of solvation necessary to
      stabilize these clusters with respect to electron loss is substantially lower
      through ion pairing with either H+ or K+ (n = 17 and 18, respectively). IRPD
      spectra of Fe(CN)64-(H2O) n show the emergence of a free O-H water molecule
      stretch between n = 142 and 162 indicating that this ion patterns the structure
      of water molecules within these nanodrops to a distance of at least ~1.05 nm from
      the ion. These results provide new insights into how water stabilizes highly
      charged ions and demonstrate that highly charged anions can have a significant
      effect on the hydrogen-bonding network of water molecules well beyond the second
      and even third solvation shells.

PMID- 28451281
TI  - Multiple competing pathways for chemical reaction: drastic reaction shortcut for
      the self-catalytic double-helix formation of helicene oligomers.
AB  - Competition among multiple pathways in a chemical reaction exhibits notable
      kinetic phenomena, particularly when amplification by self-catalysis is involved.
      A pseudoenantiomeric 1 : 1 mixture of an aminomethylene helicene (P)-tetramer and
      an (M)-pentamer formed enantiomeric hetero-double helices B and C in solution
      when random coil A was cooled. When a solution of A at 70  degrees C was directly
      cooled to 25  degrees C, the A-to-B reaction was predominant, then B was slowly
      converted to C over 60 h. The slow conversion in the A-to-B-to-C reaction was due
      to the formation of the hetero-double helix B, which was an off-pathway
      intermediate, and the slow B-to-C conversion. In contrast, when a solution of A
      at 70  degrees C was snap-cooled to -25  degrees C before then maintaining the
      solution at 25  degrees C, the A-to-C reaction predominated, and the formation of
      C was complete within 4 h. The reactions involve competition between the self
      catalytic A-to-B and A-to-C pathways, where B and C catalyze the A-to-B and A-to
      C reactions, respectively. Subtle differences in the initial states generated by
      thermal pretreatment were amplified by the self-catalytic process, which resulted
      in a drastic reaction shortcut.

PMID- 28451282
TI  - Fluorogenic sensor platform for the histone code using receptors from dynamic
      combinatorial libraries.
AB  - Post-translational modifications (PTMs) on histone tails act in diverse
      combinations in the 'histone code' to control gene expression, with dysregulation
      observed in a variety of diseases. However, detection and sensing methods are
      limited, expensive, and/or low-throughput, including MS and antibody based
      detection. We found that by combining four synthetic receptors developed by
      dynamic combinatorial chemistry (DCC) in an indicator displacement system, we are
      able to create a pattern-based sensor platform that can discriminate single PTMs
      such as methylation and acetylation on a representative histone peptide with 100%
      accuracy as well as peptides bearing both dimethyl and trimethyl lysine in the
      presence of arginine methylation, which has not previously been demonstrated, and
      can even correctly distinguish the position of lysine methylation individually or
      in the presence of other PTMs. To extend this approach, a full panel of thirteen
      analytes containing different combinations of PTMs were classified with 96 +/- 1%
      overall accuracy in a 50% left-out analysis, demonstrating the robustness and
      versatility of the sensor array. Finally, the sensor platform was also used to
      demonstrate proof of concept for enzymatic assays by analysing the mock reaction
      of a threonine kinase, successfully identifying analytes representative of
      substrate conversion both with and without neighboring PTMs. This work provides a
      rapid platform for the analysis of peptides bearing complex modifications and
      highlights the utility of receptors discovered though DCC that display variations
      in binding affinity and selectivity.

PMID- 28451283
TI  - The opposite effects of sodium and potassium cations on water dynamics.
AB  - Water rotational dynamics in NaSCN and KSCN solutions at a series of
      concentrations are investigated using femtosecond infrared spectroscopy and
      theory. Femtosecond infrared measurements, consistent with previous NMR
      observations, detect that sodium slows down while potassium accelerates the water
      O-H bond rotation. Results of reported neutron scattering measurements, on the
      other hand, suggested that these two cations have similar structure-breaking
      effects on water, and therefore should both accelerate water rotation through the
      presumably dominating large-amplitude angular jump component. To explain this
      discrepancy, theoretical studies with both classical and ab initio models were
      carried out, which indicate that both ions indeed accelerate the large-amplitude
      angular jump rotation of the water molecules, while the observed cation specific
      effect originates from the non-negligible opposite impact of the sodium and
      potassium cations on the diffusive rotation of water molecules.

PMID- 28451284
TI  - Cryptic post-transition state bifurcations that reduce the efficiency of lactone
      forming Rh-carbenoid C-H insertions.
AB  - Byproducts of chemical reactions are generally thought to result from the
      competition between two reaction pathways, each with its own rate-determining
      transition state structure. We show here, however, that pathways with a single
      transition state structure followed by a post-transition state bifurcation may
      also be a source of undesired products, especially those whose appearance is
      unexpected. The viability of this scenario for intramolecular C-H insertion
      reactions affording beta-lactones via Rh-carbenoid intermediates is assessed
      through quantum chemical calculations on potential energy surfaces and quasi
      classical molecular dynamics simulations. It appears that, in these cases, the
      rhodium catalyst is to blame for the accessibility of a second, unintended,
      pathway following the transition state structure for beta-lactone formation that
      leads to fragmentation to a ketene and carbonyl compound. If an unexpected
      product is formed via a post-transition state bifurcation, conventional
      strategies for suppressing its formation are unlikely to succeed. Guidelines for
      recognizing the presence of a post-transition state bifurcation are described
      here, along with hints at means for controlling product distributions.

PMID- 28451285
TI  - Chemical optogenetic modulation of inflammation and immunity.
AB  - The immune system is an essential component of host defense against pathogens and
      is largely mediated by inflammatory molecules produced by immune cells, such as
      macrophages. These inflammatory mediators are regulated at the transcriptional
      level by chromatin-modifying enzymes including histone deacetylases (HDACs). Here
      we describe a strategy to regulate inflammation and immunity with photocontrolled
      HDAC inhibitors, which can be selectively delivered to target cells by UV
      irradiation to minimize off-target effects. We strategically photocaged the
      active moiety of an HDAC inhibitor and showed that mild UV irradiation leads to
      the selective release of the inhibitor in a spatiotemporal manner. This
      methodology was used to decrease the amount of pro-inflammatory mediators
      produced by a subpopulation of macrophages. Our approach could ultimately be used
      to control inflammation in vivo as a therapeutic for inflammatory diseases, while
      minimizing off-target effects to healthy tissues.

PMID- 28451286
TI  - Postsynthetic ionization of an imidazole-containing metal-organic framework for
      the cycloaddition of carbon dioxide and epoxides.
AB  - A bifunctional imidazolium functionalized zirconium metal-organic framework (Zr
      MOF), (I-)Meim-UiO-66 (2), was successfully prepared from the imidazole
      containing Zr-MOF Im-UiO-66 (1) by a post-synthetic modification (PSM) method. It
      was found that the crystal size and pore features of the imidazole-containing 1
      could be tuned at the nanoscale. The bifunctional MOF 2, containing Bronsted acid
      sites and iodide ions, was shown to be an efficient and recyclable heterogeneous
      catalyst for the cycloaddition of carbon dioxide (CO2) with epoxides, without the
      use of any co-catalyst, at ambient pressure. The solvent-free synthesis of the
      cyclic carbonate from CO2 and an epoxide was monitored by in situ Fourier
      transform infrared spectroscopy (FT-IR) and an acid/base synergistic catalysis
      mechanism was proposed. We hope that our strategy provides an effective approach
      for the introduction of functional N-heterocyclic groups into MOFs for potential
      applications.

PMID- 28451287
TI  - Conductance in a bis-terpyridine based single molecular breadboard circuit.
AB  - Controlling charge flow in single molecule circuits with multiple electrical
      contacts and conductance pathways is a much sought after goal in molecular
      electronics. In this joint experimental and theoretical study, we advance the
      possibility of creating single molecule breadboard circuits through an analysis
      of the conductance of a bis-terpyridine based molecule (TP1). The TP1 molecule
      can adopt multiple conformations through relative rotations of 7 aromatic rings
      and can attach to electrodes in 61 possible single and multi-terminal
      configurations through 6 pyridyl groups. Despite this complexity, we show that it
      is possible to extract well defined conductance features for the TP1 breadboard
      and assign them rigorously to the underlying constituent circuits. Mechanically
      controllable break-junction (MCBJ) experiments on the TP1 molecular breadboard
      show an unprecedented 4 conductance states spanning a range 10 -2G0 to 10 -7G0.
      Quantitative theoretical examination of the conductance of TP1 reveals that
      combinations of 5 types of single terminal 2-5 ring subcircuits are accessed as a
      function of electrode separation to produce the distinct conductance steps
      observed in the MCBJ experiments. We estimate the absolute conductance for each
      single terminal subcircuit and its percentage contribution to the 4
      experimentally observed conductance states. We also provide a detailed analysis
      of the role of quantum interference and thermal fluctuations in modulating
      conductance within the subcircuits of the TP1 molecular breadboard. Finally, we
      discuss the possible development of molecular circuit theory and experimental
      advances necessary for mapping conductance through complex single molecular
      breadboard circuits in terms of their constituent subcircuits.

PMID- 28451288
TI  - Insights into ClpXP proteolysis: heterooligomerization and partial deactivation
      enhance chaperone affinity and substrate turnover in Listeria monocytogenes.
AB  - Caseinolytic proteases (ClpP) are important for recognition and controlled
      degradation of damaged proteins. While the majority of bacterial organisms
      utilize only a single ClpP, Listeria monocytogenes expresses two isoforms
      (LmClpP1 and LmClpP2). LmClpPs assemble into either a LmClpP2 homocomplex or a
      LmClpP1/2 heterooligomeric complex. The heterocomplex in association with the
      chaperone ClpX, exhibits a boost in proteolytic activity for unknown reasons.
      Here, we use a combined chemical and biochemical strategy to unravel two
      activation principles of LmClpPs. First, determination of apparent affinity
      constants revealed a 7-fold elevated binding affinity between the LmClpP1/2
      heterocomplex and ClpX, compared to homooligomeric LmClpP2. This tighter
      interaction favors the formation of the proteolytically active complex between
      LmClpX and LmClpP1/2 and thereby accelerating the overall turnover. Second,
      screening a diverse library of fluorescent labeled peptides and proteins with
      various ClpP mutants allowed the individual analysis of substrate preferences for
      both isoforms within the heterocomplex. In addition to Leu and Met, LmClpP2
      preferred a long aliphatic chain (2-Aoc) in the P1 position for cleavage.
      Strikingly, design and synthesis of a corresponding 2-Aoc chloromethyl ketone
      inhibitor resulted in stimulation of proteolysis by 160% when LmClpP2 was
      partially alkylated on 20% of the active sites. Determination of apparent
      affinity constants also revealed an elevated complex stability between partially
      modified LmClpP2 and the cognate chaperone LmClpX. Thus, the stimulation of
      proteolysis through enhanced binding to the chaperone seems to be a
      characteristic feature of LmClpPs.

PMID- 28451289
TI  - Metal-free O-H/C-H difunctionalization of phenols by o-hydroxyarylsulfonium salts
      in water.
AB  - An environmentally benign method for C-H/O-H difunctionalization of phenols with
      sulfoxides under mild conditions has been developed. The reaction process is
      mediated by an electrophilic aromatic substitution and subsequent selective aryl
      or alkyl migration, involving C-S and C-O bond formations with broad substrate
      scope.

PMID- 28451290
TI  - Activation and characterization of a cryptic gene cluster reveals a cyclization
      cascade for polycyclic tetramate macrolactams.
AB  - Polycyclic tetramate macrolactams (PTMs) are a growing class of natural products
      and are derived from a hybrid polyketide synthase (PKS)/non-ribosomal peptide
      synthetase (NRPS) pathway. PTM biosynthetic gene clusters are conserved and
      widely distributed in bacteria, however, most of them remain silent. Herein we
      report the activation of a PTM gene cluster in marine-derived Streptomyces pactum
      SCSIO 02999 by promoter engineering and heterologous expression, leading to the
      discovery of six new PTMs, pactamides A-F (11-16), with potent cytotoxic activity
      upon several human cancer cell lines. In vivo gene disruption experiments and in
      vitro biochemical assays reveal a reductive cyclization cascade for polycycle
      formation, with reactions sequentially generating the 5, 5/5 and 5/5/6
      carbocyclic ring systems, catalysed by the phytoene dehydrogenase PtmB2, the
      oxidoreductase PtmB1, and the alcohol dehydrogenase PtmC, respectively.
      Furthermore, PtmC was demonstrated as a bifunctional cyclase for catalyzing the
      formation of the inner five-membered ring in ikarugamycin. This study suggests
      the possibility of finding more bioactive PTMs by genome mining and discloses a
      general mechanism for the formation of 5/5/6-type carbocyclic rings in PTMs.

PMID- 28451291
TI  - Photoredox radical conjugate addition of dithiane-2-carboxylate promoted by an
      iridium(iii) phenyl-tetrazole complex: a formal radical methylation of Michael
      acceptors.
AB  - A readily accessible iridium(iii) phenyl-tetrazole complex ([Ir(ptrz)2(tBu
      bpy)]+, 2; Hptrz = 2-methyl-5-phenyl-tetrazole; tBu-bpy = 4,4'-di-tert-butyl-2,2'
      bipyridine) is shown to be a versatile catalyst for a new photocatalytic Michael
      reaction. Under light irradiation in the presence of 2, a dithiane 2-carboxylic
      acid, obtained by simple hydrolysis of a commercially available ethyl ester,
      generates a 1,3-dithiane radical capable of performing addition to a variety of
      Michael acceptors (e.g., unsaturated ketones, esters, amides and malonates). This
      broad scope reaction with high yields is a formal photo-redox addition of the
      elusive methyl radical and the adducts obtained can be starting materials for a
      variety of functionalized products. The excited-state oxidation potential of
      catalyst 2 allows selective formation of radicals only from alpha
      heterosubstituted carboxylates. Chemical modification of this metal complex can
      tune the electrochemical properties, opening a route to new highly selective
      catalytic photo-oxidation reactions.

PMID- 28451292
TI  - Polydopamine and eumelanin molecular structures investigated with ab initio
      calculations.
AB  - A set of computational methods that contains a brute-force algorithmic generation
      of chemical isomers, molecular dynamics (MD) simulations, and density functional
      theory (DFT) calculations is reported and applied to investigate nearly 3000
      probable molecular structures of polydopamine (PDA) and eumelanin. All probable
      early-polymerized 5,6-dihydroxyindole (DHI) oligomers, ranging from dimers to
      tetramers, have been systematically analyzed to find the most stable geometry
      connections as well as to propose a set of molecular models that represents the
      chemically diverse nature of PDA and eumelanin. Our results indicate that more
      planar oligomers have a tendency to be more stable. This finding is in good
      agreement with recent experimental observations, which suggested that PDA and
      eumelanin are composed of nearly planar oligomers that appear to be stacked
      together via pi-pi interactions to form graphite-like layered aggregates. We also
      show that there is a group of tetramers notably more stable than the others,
      implying that even though there is an inherent chemical diversity in PDA and
      eumelanin, the molecular structures of the majority of the species are quite
      repetitive. Our results also suggest that larger oligomers are less likely to
      form. This observation is also consistent with experimental measurements,
      supporting the existence of small oligomers instead of large polymers as main
      components of PDA and eumelanin. In summary, this work brings an insight into the
      controversial structure of PDA and eumelanin, explaining some of the most
      important structural features, and providing a set of molecular models for more
      accurate modeling of eumelanin-like materials.

PMID- 28451293
TI  - A full set of iridium(iv) pyridine-alkoxide stereoisomers: highly geometry
      dependent redox properties.
AB  - We introduce and characterize the complete set of possible isomers of
      IrIV(pyalk)2Cl2 (pyalk = 2-(pyridin-2-yl)propan-2-oate), providing valuable
      insights on the properties of Ir(iv) species. The pyridine alkoxide ligand
      strongly stabilizes high oxidation states, essential to accessing the
      catalytically relevant Ir(iv) state, and results in robust complexes that can be
      handled under ambient conditions, even permitting chromatographic separation. The
      redox properties are isomer-dependent, spanning a 300 mV range, rationalized with
      ligand-field theory and DFT calculations. The reported complexes exhibit very
      high kinetic inertness against isomerization, despite highly disparate predicted
      thermodynamic stabilities, presenting a unique opportunity to study all five
      possible isomeric complexes with the same ligand set.

PMID- 28451294
TI  - To catalyze or not to catalyze: elucidation of the subtle differences between the
      hexameric capsules of pyrogallolarene and resorcinarene.
AB  - The closely related, self-assembled resorcinarene and pyrogallolarene capsules
      display contrasting and puzzling encapsulation behaviors. Herein, we elucidate
      the reasons for these differences by combining experimental studies and DFT
      calculations. Furthermore, we report that, in contrast to the resorcinarene
      capsule, the pyrogallolarene derivative is not capable of catalyzing reactions
      with cationic transition states. The molecular mechanisms responsible for these
      observations are probed in detail.

PMID- 28451295
TI  - Design of a synthetic luminescent probe from a biomolecule binding domain:
      selective detection of AU-rich mRNA sequences.
AB  - We report the design of a luminescent sensor based upon the zinc finger (ZF)
      protein TIS11d, that allows for the selective time-resolved detection of the
      UUAUUUAUU sequence of the 3'-untranslated region of messenger RNA. This sensor is
      composed of the tandem ZF RNA binding domain of TIS11d functionalized with a
      luminescent Tb3+ complex on one of the ZFs and a sensitizing antenna on the
      other. This work provides the proof of principle that an RNA binding protein can
      be re-engineered as an RNA sensor and, more generally, that tunable synthetic
      luminescent probes for biomolecules can be obtained by modifying biomolecule
      binding domains.

PMID- 28451296
TI  - Mechanism of water transport in graphene oxide laminates.
AB  - It is understood that nano-channels of graphene oxide membranes have a water flow
      mechanism which is similar to the water flow inside carbon nanotube pores. The
      water transport mechanisms recently proposed by various researchers suggest that
      membranes composed of graphene oxide laminates could be regarded as an assembly
      of many tiny carbon nanotubes stacked together with attached functional groups as
      spacers.

PMID- 28451299
TI  - Charge transfer dynamics in DNA revealed by time-resolved spectroscopy.
AB  - In the past few decades, charge transfer in DNA has attracted considerable
      attention from researchers in a wide variety of fields, including bioscience,
      physical chemistry, and nanotechnology. Charge transfer in DNA has been
      investigated using various techniques. Among them, time-resolved spectroscopic
      methods have yielded valuable information on charge transfer dynamics in DNA,
      providing an important basis for numerical practical applications such as
      development of new therapy applications and nanomaterials. In DNA, holes and
      excess electrons act as positive and negative charge carriers, respectively.
      Although hole transfer dynamics have been investigated in detail, the dynamics of
      excess electron transfer have only become clearer relatively recently. In the
      present paper, we summarize studies on the dynamics of hole and excess electron
      transfer conducted by several groups including our own.

PMID- 28451298
TI  - Enrichment and single-cell analysis of circulating tumor cells.
AB  - Up to 90% of cancer-related deaths are caused by metastatic cancer. Circulating
      tumor cells (CTCs), a type of cancer cell that spreads through the blood after
      detaching from a solid tumor, are essential for the establishment of distant
      metastasis for a given cancer. As a new type of liquid biopsy, analysis of CTCs
      offers the possibility to avoid invasive tissue biopsy procedures with practical
      implications for diagnostics. The fundamental challenges of analyzing and
      profiling CTCs are the extremely low abundances of CTCs in the blood and the
      intrinsic heterogeneity of CTCs. Various technologies have been proposed for the
      enrichment and single-cell analysis of CTCs. This review aims to provide in-depth
      insights into CTC analysis, including various techniques for isolation of CTCs
      with capture methods based on physical and biochemical principles, and single
      cell analysis of CTCs at the genomic, proteomic and phenotypic level, as well as
      current developmental trends and promising research directions.

PMID- 28451297
TI  - Immunological properties of gold nanoparticles.
AB  - In the past decade, gold nanoparticles have attracted strong interest from the
      nanobiotechnological community owing to the significant progress made in robust
      and easy-to-make synthesis technologies, in surface functionalization, and in
      promising biomedical applications. These include bioimaging, gene diagnostics,
      analytical sensing, photothermal treatment of tumors, and targeted delivery of
      various biomolecular and chemical cargos. For the last-named application, gold
      nanoparticles should be properly fabricated to deliver the cargo into the
      targeted cells through effective endocytosis. In this review, we discuss recent
      progress in understanding the selective penetration of gold nanoparticles into
      immune cells. The interaction of gold nanoparticles with immune cell receptors is
      discussed. As distinct from other published reviews, we present a summary of the
      immunological properties of gold nanoparticles. This review also summarizes what
      is known about the application of gold nanoparticles as an antigen carrier and
      adjuvant in immunization for the preparation of antibodies in vivo. For each of
      the above topics, the basic principles, recent advances, and current challenges
      are discussed. Thus, this review presents a detailed analysis of data on
      interaction of gold nanoparticles with immune cells. Emphasis is placed on the
      systematization of data over production of antibodies by using gold nanoparticles
      and adjuvant properties of gold nanoparticles. Specifically, we start our
      discussion with current data on interaction of various gold nanoparticles with
      immune cells. The next section describes existing technologies to improve
      production of antibodies in vivo by using gold nanoparticles conjugated with
      specific ligands. Finally, we describe what is known about adjuvant properties of
      bare gold or functionalized nanoparticles. In the Conclusion section, we present
      a short summary of reported data and some challenges and perspectives.

PMID- 28451300
TI  - Chirality controlled responsive self-assembled nanotubes in water.
AB  - The concept of using chirality to dictate dimensions and to store chiral
      information in self-assembled nanotubes in a fully controlled manner is
      presented. We report a photoresponsive amphiphile that co-assembles with its
      chiral counterpart to form nanotubes and demonstrate how chirality can be used to
      effect the formation of either micrometer long, achiral nanotubes or shorter
      (~300 nm) chiral nanotubes that are bundled. The nature of these assemblies is
      studied using a variety of spectroscopic and microscopic techniques and it is
      shown that the tubes can be disassembled with light, thereby allowing the chiral
      information to be erased.

PMID- 28451302
TI  - Iridium-catalyzed asymmetric hydrogenation of racemic alpha-substituted lactones
      to chiral diols.
AB  - We report a protocol for the highly efficient iridium-catalyzed asymmetric
      hydrogenation of racemic alpha-substituted lactones via dynamic kinetic
      resolution. Using Ir-SpiroPAP (R)-1d as a catalyst, a wide range of chiral diols
      were prepared in a high yield (80-95%) with a high enantioselectivity (up to 95%
      ee) under mild reaction conditions. This protocol was used for enantioselective
      syntheses of (-)-preclamol and a chiral 2,5-disubstituted tetrahydropyran.

PMID- 28451301
TI  - Room temperature decarboxylative cyanation of carboxylic acids using photoredox
      catalysis and cyanobenziodoxolones: a divergent mechanism compared to
      alkynylation.
AB  - The one-step conversion of aliphatic carboxylic acids to the corresponding
      nitriles has been accomplished via the merger of visible light mediated
      photoredox and cyanobenziodoxolones (CBX) reagents. The reaction proceeded in
      high yields with natural and non-natural alpha-amino and alpha-oxy acids,
      affording a broad scope of nitriles with excellent tolerance of the substituents
      in the alpha position. The direct cyanation of dipeptides and drug precursors was
      also achieved. The mechanism of the decarboxylative cyanation was investigated
      both computationally and experimentally and compared with the previously
      developed alkynylation reaction. Alkynylation was found to favor direct radical
      addition, whereas further oxidation by CBX to a carbocation and cyanide addition
      appeared more favorable for cyanation. A concerted mechanism is proposed for the
      reaction of radicals with EBX reagents, in contrast to the usually assumed
      addition elimination process.

PMID- 28451303
TI  - Near-IR-induced dissociation of thermally-sensitive star polymers.
AB  - Responsive systems sensitive to near-infrared (NIR) light are promising for
      triggered release due to efficient deep tissue penetration of NIR irradiation
      relative to higher energy sources (e.g., UV), allowing for spatiotemporal control
      over triggering events with minimal potential for tissue damage. Herein, we
      report star polymers containing thermally-labile azo linkages that dissociate
      during conventional heating or during localized heating via the photothermal
      effect upon NIR irradiation. Controlled release during conventional heating was
      investigated for the star polymers loaded with a model dye, with negligible
      release being observed at 25  degrees C and >80% release at 90  degrees C. Star
      polymers co-loaded with NIR-responsive indocyanine green showed rapid dye release
      upon NIR irradiation (lambda >= 715 nm) due to the photothermally-induced
      degradation of azo linkages within the cores of the star polymers. This approach
      provides access to a new class of delivery and release systems that can be
      triggered by noninvasive external stimulation.

PMID- 28451304
TI  - Simultaneous impedance spectroscopy and fluorescence microscopy for the real-time
      monitoring of the response of cells to drugs.
AB  - A dual fluorescence microscopy and electrochemical strategy to investigate how
      cell-surface interactions influence the cellular responses to cues for the cell
      based biosensing of drug efficacy is reported herein. The combined method can be
      used to not only monitor the importance of controlling the cellular adhesive
      environment on the cell response to drugs but it also provides biological
      information on the timescales of downstream outside-in signaling from soluble
      cues. As an example of the use of the combined method, we show how adhesive cues
      influence the signalling responses of cells to soluble cues. G-protein-coupled
      receptors were used as the target for the soluble cues. The changes in cell
      adhesion, cell morphology and Ca2+ flux induced by soluble histamine were
      simultaneously monitored as a function of the spacing of the adhesive ligand RGD
      on the interdigitated indium tin oxide electrodes. The simultaneous measurements
      revealed that the timescales of histamine-induced Ca2+ mobilization and the
      decrease in cell-cell adhesions are correlated. Furthermore, cells on the
      surfaces with an RGD spacing of 31 nm were shown to display a faster release of
      Ca2+ and change in cell adhesion upon histamine stimulation compared to cells on
      other surfaces.

PMID- 28451305
TI  - Responsive hetero-organelle partition conferred fluorogenic sensing of
      mitochondrial depolarization.
AB  - Malfunctioning organelles are often difficult to probe with classical organelle
      homing sensors owing to disruption of physiological organelle-probe affinity. We
      herein report the use of a responsive hetero-organelle partition and signal
      activable probe (RC-TPP) for detecting mitochondrial depolarization, a
      pathologically relevant event featuring loss of the electrical potentials across
      the mitochondrial membrane (DeltaPsim). Partitioned in mitochondria to give blue
      fluorescence, RC-TPP relocates into lysosomes upon mitochondrial depolarization
      and exhibits red fluorescence triggered by lysosomal acidity, enabling
      determination of autophagy relevant mitochondrial depolarization and the
      chronological sequence of mitochondrial depolarization and lysosomal
      neutralization in distinct cell death signalling pathways. As an alternative to
      classic homo-organelle specific molecular systems, this hetero-organelle
      responsive approach provides a new perspective from which to study dysfunctional
      organelles.

PMID- 28451306
TI  - Accessing human selenoproteins through chemical protein synthesis.
AB  - The human body contains 25 selenoproteins, which contain in their sequence the
      twenty-first encoded amino acid, selenocysteine. About a dozen of these proteins
      remain functionally uncharacterized or poorly studied. Challenges in accessing
      these selenoproteins using traditional recombinant expressions have prevented
      biological characterization thus far. Chemical protein synthesis has the
      potential to overcome these hurdles. Here we report the first total chemical
      syntheses of two human selenoproteins, selenoprotein M (SELM) and selenoprotein W
      (SELW). The synthesis of the more challenging protein SELM was enabled using
      recent advances in the field of selenocysteine chemistry. This approach allows
      the preparation of selenoproteins in milligram quantities and in homogenous form,
      which should open new horizons for future studies to pursue a fuller biological
      understanding of their role in health and disease.

PMID- 28451307
TI  - Bimodal supramolecular functionalization of carbon nanotubes triggered by
      covalent bond formation.
AB  - Many applications of carbon nanotubes require their chemical functionalization.
      Both covalent and supramolecular approaches have been extensively investigated. A
      less trodden path is the combination of both covalent and noncovalent
      chemistries, where the formation of covalent bonds triggers a particularly stable
      noncovalent interaction with the nanotubes. We describe a series of naphthalene
      diimide (NDI) bisalkene molecules that, upon mixing with single-walled carbon
      nanotubes (SWNTs) and Grubbs' catalyst, undergo two different reaction pathways.
      On one hand, they ring-close around the SWNTs to form rotaxane-like mechanically
      interlocked derivatives of SWNTs (MINTs). Alternatively, they oligomerize and
      then wrap around the SWNTs. The balance of MINTs to oligomer-wrapped SWNTs
      depends on the affinity of the NDI molecules for the SWNTs and the kinetics of
      the metathesis reactions, which can be controlled by varying the solvent.
      Thorough characterization of the products (TGA, TEM, AFM, Raman, UV-vis-NIR, PLE,
      XPS and UPS) confirms their structure and shows that each type of
      functionalization affects the electronic properties of the SWNTs differently.

PMID- 28451308
TI  - N-Heterocyclic carbene-catalyzed oxidative [3 + 2] annulation of dioxindoles and
      enals: cross coupling of homoenolate and enolate.
AB  - The N-heterocyclic carbene-catalyzed oxidative [3 + 2] annulation of dioxindole
      and enals was developed, giving the corresponding spirocyclic oxindole-gamma
      lactones in good yields with high to excellent diastereo- and
      enantioselectivities. The challenging aliphatic enals worked effectively using
      this strategy. The oxidative cross coupling of homoenolate and enolate via single
      electron transfer was proposed as the key step for the reaction.

PMID- 28451309
TI  - A multi-functional PEGylated gold(iii) compound: potent anti-cancer properties
      and self-assembly into nanostructures for drug co-delivery.
AB  - Gold(iii) porphyrin-PEG conjugates [Au(TPP-COO-PEG5000-OCH3)]Cl (1) and [Au(TPP
      CONH-PEG5000-OCH3)]Cl (2) have been synthesized and characterized. Based on the
      amphiphilic character of the conjugates, they were found to undergo self-assembly
      into nanostructures with size 120-200 nm and this did not require the presence of
      other surfactants or components for nano-assembly, unlike most conventional drug
      nano-formulations. With a readily hydrolyzable ester linkage, chemotherapeutic
      [Au(TPP-COOH)]+ exhibited triggered release from the conjugate 1 in acidic buffer
      solution as well as in vitro and in vivo without the formation of toxic side
      products. The nanostructures of 1 showed higher cellular uptake into cancer cells
      compared to non-tumorigenic cells, owing to their energy-dependent uptake
      mechanism. This, together with a generally higher metabolic rate and more acidic
      nature of cancer cells which can lead to faster hydrolysis of the ester bond,
      afforded 1 with excellent selectivity in killing cancer cells compared with non
      tumorigenic cells in vitro. This was corroborated by fluorescence microscopy
      imaging and flow cytometric analysis of co-culture model of colon cancer (HCT116)
      and normal colon (NCM460) cells. In vivo experiments showed that treatment of
      nude mice bearing HCT116 xenografts with 1 resulted in significant inhibition of
      tumor growth and, more importantly, minimal systemic toxicity as revealed by
      histopathological analysis of tissue sections and blood biochemisty. The latter
      is explained by a lower accumulation of 1 in organs of treated mice at its
      effective dosage, as compared to that of other gold(iii) porphyrin complexes. Co
      assembly of 1 and doxorubicin resulted in encapsulation of doxorubicin by the
      nanostructures of 1. The nanocomposites demonstrated a strong synergism on
      killing cancer cells and could overcome efflux pump-mediated drug-resistance in a
      doxorubicin-resistant ovarian cancer cell line (A2780adr) which was found in
      cells incubated with doxorubicin alone. Also, the nanocomposites accumulated more
      slowly in non-tumorigenic cells, resulting in a lower toxicity toward non
      tumorigenic cells. These results indicate the potential application of 1 not only
      as an anti-cancer agent but also as a nanoscale drug carrier for chemotherapy.

PMID- 28451310
TI  - Toward a mild dehydroformylation using base-metal catalysis.
AB  - Dehydroformylation, or the reaction of aldehydes to produce alkenes, hydrogen
      gas, and carbon monoxide, is a powerful transformation that is underdeveloped
      despite the high industrial importance of the reverse reaction, hydroformylation.
      Interestingly, nature routinely performs a related transformation, oxidative
      dehydroformylation, in the biosynthesis of cholesterol and related sterols under
      mild conditions using base-metal catalysts. In contrast, chemists have recently
      developed a non-oxidative dehydroformylation method; however, it requires high
      temperatures and a precious-metal catalyst. Careful study of both approaches has
      informed our efforts to design a base-metal catalyzed, mild dehydroformylation
      method that incorporates benefits from each while avoiding several of their
      respective disadvantages. Importantly, we show that cooperative base metal
      catalysis presents a powerful, mechanistically unique approach to reactions which
      are difficult to achieve using conventional catalyst design.

PMID- 28451311
TI  - Decreasing the electronic confinement in layered perovskites through
      intercalation.
AB  - We show that post-synthetic small-molecule intercalation can significantly reduce
      the electronic confinement of 2D hybrid perovskites. Using a combined
      experimental and theoretical approach, we explain structural, optical, and
      electronic effects of intercalating highly polarizable molecules in layered
      perovskites designed to stabilize the intercalants. Polarizable molecules in the
      organic layers substantially alter the optical and electronic properties of the
      inorganic layers. By calculating the spatially resolved dielectric profiles of
      the organic and inorganic layers within the hybrid structure, we show that the
      intercalants afford organic layers that are more polarizable than the inorganic
      layers. This strategy reduces the confinement of excitons generated in the
      inorganic layers and affords the lowest exciton binding energy for an n = 1
      perovskite of which we are aware. We also demonstrate a method for
      computationally evaluating the exciton's binding energy by solving the Bethe
      Salpeter equation for the exciton, which includes an ab initio determination of
      the material's dielectric profile across organic and inorganic layers. This new
      semi-empirical method goes beyond the imprecise phenomenological approximation of
      abrupt dielectric-constant changes at the organic-inorganic interfaces. This work
      shows that incorporation of polarizable molecules in the organic layers, through
      intercalation or covalent attachment, is a viable strategy for tuning 2D
      perovskites towards mimicking the reduced electronic confinement and isotropic
      light absorption of 3D perovskites while maintaining the greater synthetic
      tunability of the layered architecture.

PMID- 28451312
TI  - Development of a novel lysosome-targetable time-gated luminescence probe for
      ratiometric and luminescence lifetime detection of nitric oxide in vivo.
AB  - Rapid, multiplexed, sensitive and specific identification and quantitative
      detection of nitric oxide (NO) are in great demand in biomedical science. Herein,
      a novel multifunctional probe based on the intramolecular LRET (luminescence
      resonance energy transfer) strategy, TRP-NO, was designed for the highly
      sensitive and selective ratiometric and luminescence lifetime detection of
      lysosomal NO. Before reaction with NO, the emission of the rhodamine moiety in
      TRP-NO is switched off, which prevents the LRET process, so that the probe emits
      only the long-lived Tb3+ luminescence. However, upon reaction with NO,
      accompanied by the turn-on of rhodamine emission, the LRET from the Tb3+-complex
      moiety to rhodamine moiety occurs, which results in a remarkable increase of the
      rhodamine emission and decrease of the Tb3+ emission. After the reaction, the
      intensity ratio of the rhodamine emission to the Tb3+ emission, I565/I540, was
      found to be 28.8-fold increased, and the dose-dependent enhancement of the
      I565/I540 value showed a good linearity upon the increase of NO concentration. In
      addition, a dose-dependent luminescence lifetime decrease was distinctly observed
      between the average luminescence lifetime of the probe and NO concentration,
      which provides a ~10-fold contrast window for the detection of NO. These unique
      properties allowed TRP-NO to be conveniently used as a time-gated luminescence
      probe for the quantitative detection of NO using both luminescence intensity
      ratio and luminescence lifetime as signals. The applicability of TRP-NO for
      ratiometric time-gated luminescence imaging of NO in living cells was
      investigated. Meanwhile, dye co-localization studies confirmed a quite precise
      distribution of TRP-NO in lysosomes by confocal microscopy imaging. Furthermore,
      the practical applicability of TRP-NO was demonstrated by the visualization of NO
      in Daphnia magna. All of the results demonstrated that TRP-NO could serve as a
      useful tool for exploiting and elucidating the function of NO at sub-cellular
      levels with high specificity, accuracy and contrast.

PMID- 28451313
TI  - Neutral iridium catalysts with chiral phosphine-carboxy ligands for asymmetric
      hydrogenation of unsaturated carboxylic acids.
AB  - We developed neutral iridium catalysts with chiral spiro phosphine-carboxy
      ligands (SpiroCAP) for asymmetric hydrogenation of unsaturated carboxylic acids.
      Different from the cationic Crabtree-type catalysts, the iridium catalysts with
      chiral spiro phosphine-carboxy ligands are neutral and do not require the use of
      a tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF-) counterion, which is
      necessary for stabilizing cationic Crabtree-type catalysts. Another advantage of
      the neutral iridium catalysts is that they have high stability and have a long
      lifetime in air. The new iridium catalysts with chiral spiro phosphine-carboxy
      ligands exhibit unprecedented high enantioselectivity (up to 99.4% ee) in the
      asymmetric hydrogenations of various unsaturated carboxylic acids, particularly
      for 3-alkyl-3-methylenepropionic acids, which are challenging substrates for
      other chiral catalysts.

PMID- 28451314
TI  - Enantioselective Narasaka-Heck cyclizations: synthesis of tetrasubstituted
      nitrogen-bearing stereocenters.
AB  - The first examples of highly enantioselective Narasaka-Heck cyclizations are
      described. A SPINOL-derived P,N-ligand system enables Pd-catalyzed 5-exo
      cyclization of a range of oxime esters with sterically diverse trisubstituted
      alkenes to generate dihydropyrroles containing tetrasubstituted nitrogen-bearing
      stereocenters in 56 to 86% yield and 90 : 10 to 95 : 5 e.r. These processes are
      rare examples of reactions that proceed via enantioselective migratory insertion
      of alkenes into Pd-N bonds, and the first where trisubstituted alkenes are used
      to generate tetrasubstituted stereocenters with high enantioselectivity.

PMID- 28451315
TI  - Engineering proximal vs. distal heme-NO coordination via dinitrosyl dynamics:
      implications for NO sensor design.
AB  - Proximal vs. distal heme-NO coordination is a novel strategy for selective gas
      response in heme-based NO-sensors. In the case of Alcaligenes xylosoxidans
      cytochrome c' (AXCP), formation of a transient distal 6cNO complex is followed by
      scission of the trans Fe-His bond and conversion to a proximal 5cNO product via a
      putative dinitrosyl species. Here we show that replacement of the AXCP distal
      Leu16 residue with smaller or similar sized residues (Ala, Val or Ile) traps the
      distal 6cNO complex, whereas Leu or Phe residues lead to a proximal 5cNO product
      with a transient or non-detectable distal 6cNO precursor. Crystallographic,
      spectroscopic, and kinetic measurements of 6cNO AXCP complexes show that
      increased distal steric hindrance leads to distortion of the Fe-N-O angle and
      flipping of the heme 7-propionate. However, it is the kinetic parameters of the
      distal NO ligand that determine whether 6cNO or proximal 5cNO end products are
      formed. Our data support a 'balance of affinities' mechanism in which proximal
      5cNO coordination depends on relatively rapid release of the distal NO from the
      dinitrosyl precursor. This mechanism, which is applicable to other proteins that
      form transient dinitrosyls, represents a novel strategy for 5cNO formation that
      does not rely on an inherently weak Fe-His bond. Our data suggest a general means
      of engineering selective gas response into biologically-derived gas sensors in
      synthetic biology.

PMID- 28451316
TI  - Quantitative self-powered electrochromic biosensors.
AB  - Self-powered sensors are analytical devices able to generate their own energy,
      either from the sample itself or from their surroundings. The conventional
      approaches rely heavily on silicon-based electronics, which results in increased
      complexity and cost, and prevents the broader use of these smart systems. Here we
      show that electrochromic materials can overcome the existing limitations by
      simplifying device construction and avoiding the need for silicon-based
      electronics entirely. Electrochromic displays can be built into compact self
      powered electrochemical sensors that give quantitative information readable by
      the naked eye, simply controlling the current path inside them through a
      combination of specially arranged materials. The concept is validated by a
      glucose biosensor coupled horizontally to a Prussian blue display designed as a
      distance-meter proportional to (glucose) concentration. This approach represents
      a breakthrough for self-powered sensors, and extends the application of
      electrochromic materials beyond smart windows and displays, into sensing and
      quantification.

PMID- 28451317
TI  - A resorcinarene for inhibition of Abeta fibrillation.
AB  - Amyloid-beta peptides (Abeta) fibrillation is the hallmark of Alzheimer's disease
      (AD). However, it has been challenging to discover potent agents in order to
      inhibit Abeta fibrillation. Herein, we demonstrated the effect of resorcinarene
      on inhibiting Abeta fibrillation in vitro via experimental and computational
      methods. Abeta were incubated with different concentrations of resorcinarene so
      as to monitor the kinetics by using thioflavin T binding assay. The results,
      which were further confirmed by far-UV CD spectroscopy and atomic force
      microscopy, strongly indicated that the higher concentration of resorcinarene,
      the more effective the inhibition of Abeta fibrillation. A cytotoxicity study
      showed that when sea urchin embryos were exposed to the resorcinarene, the
      majority survived due to the resorcinarene low toxicity. In addition, when the
      resorcinarene was added, the formation of toxic Abeta 42 species was delayed.
      Computational studies of Abeta fibrillation, including docking simulations and MD
      simulations, illustrated that the interaction between inhibitor resorcinarene and
      Abeta is driven by the non-polar interactions. These studies display a novel
      strategy for the exploration of promising antiamyloiddogenic agents for AD
      treatments.

PMID- 28451318
TI  - Covalent tethering of photo-responsive superficial layers on hydrogel surfaces
      for photo-controlled release.
AB  - The diffusion and transport of substances between a hydrogel and its environment
      have received tremendous research interest, due to the wide range of applications
      of hydrogel materials in fields related to drug carriers and drug delivery
      vehicles. To date, much research has been done to tailor the diffusion and
      transport of substances through hydrogels, where most efforts were focused on
      tuning the 3D network properties of the hydrogel including loop size,
      hydrophobicity of building blocks and the stimuli-responsive properties of
      backbones. These conventional strategies, however, usually suffer from
      complicated fabrication procedures and result in a homogeneous increase in
      hydrophobicity of the hydrogel network, leading to low efficiency control over
      the diffusion of substances through the hydrogel. Herein, a facile strategy that
      can functionalize the surfaces of hydrogels, while keeping the interior network
      unchanged, was reported, and is realized by quaternization reaction confined to
      the hydrogel/oil interface. Owing to the introduction of the photo-responsive
      molecule IBSP as a modifier, the surface wettability of the resulting hydrogel
      can be controlled by light both in air and underwater environments. Consequently,
      the diffusion rate of a substance through this modified hydrogel can be regulated
      by light, which brings convenience to the controlled release of hydrogels and
      other hydrogel-related fields.

PMID- 28451319
TI  - Donor-acceptor-acceptor (D-A-A) type 1,8-naphthalimides as non-fullerene small
      molecule acceptors for bulk heterojunction solar cells.
AB  - Donor-acceptor-acceptor (D-A-A) type 1,8-naphthalimide based small molecules SM1
      and SM2 functionalized with tetracyanobutadiene (TCBD) and dicyanoquino-dimethane
      (DCNQ) modules, showing strong absorption in the visible and near-infrared (NIR)
      region are reported. TCBD and DCNQ linked SM1 and SM2 exhibit multi-redox waves.
      The electrochemical and optical HOMO-LUMO gaps show similar trends. These SMs
      exhibit a broad absorption profile which is complementary to the D-A copolymer P
      donor and also possess an appropriate lowest unoccupied molecular orbital (LUMO)
      to serve as an acceptor with P with a LUMO level of -3.33 eV. The organic solar
      cells based on P:SM1 and P:SM2 exhibit a PCE of 4.94% and 6.11%, respectively.
      The higher value of the PCE for the SM2 based organic solar cells has been
      attributed to the broader absorption profile, more balanced charge transport and
      lower photon energy loss. The values of Voc of the organic solar cells for the
      SM1 acceptor (1.06 V and 1.02 V without and with solvent additive) are the
      highest values reported for devices based on non-fullerene acceptors to the best
      of our knowledge. The energy loss (Eloss) of 0.56 eV and 0.48 eV for SM1 and SM2
      based devices, respectively is one of the smallest reported for BHJ organic solar
      cells.

PMID- 28451320
TI  - Theoretical basis for the stabilization of charges by radicals on electrified
      polymers.
AB  - Quantum mechanical calculations at various levels of theory indicate that charges
      (both "+" and "-") on organic polymers can be stabilized by radicals on nearby
      polymer chains. The stabilization mechanism is based on the formation of
      intermolecular odd-electron, two-center bonds with possible concomitant spin
      density redistribution (depending on the polymer and the number and type of
      proximal heteroatoms). This result is in line with our previous experimental
      demonstrations that on various types of polymers charged by contact
      electrification, radicals co-localize and help stabilize proximal charges (of
      either polarity). The principle of intramolecular charge-radical stabilization we
      now confirm on a fundamental level might have ramifications for the design of
      other macromolecular systems in which chemical reactivity is controlled by
      radicals flanking the charged groups or by charged groups flanking the radicals.

PMID- 28451321
TI  - Expedient synthesis of the heneicosasaccharyl mannose capped arabinomannan of the
      Mycobacterium tuberculosis cellular envelope by glycosyl carbonate donors.
AB  - The global incidence of tuberculosis is increasing at an alarming rate, and
      Mycobacterium tuberculosis (Mtb) is the causative agent for tuberculosis, a
      disease with high mortality. Lipoarabinomannan (LAM) is one of the major
      components of the Mtb cellular envelope and is an attractive scaffold for
      developing anti-tubercular drugs, vaccines and diagnostics. Herein, a highly
      convergent strategy is developed to synthesize heneicosasaccharyl arabinomannan
      for the first time. The arabinomannan synthesized in this endeavour has several
      1,2-trans or alpha-Araf linkages and three 1,2-cis or beta-Araf linkages end
      capped with 1,2-trans or alpha-Manp linkages. All the key glycosidations were
      performed with alkynyl carbonate glycosyl donors under [Au]/[Ag] catalysis
      conditions, which gave excellent yields and stereoselectivity even for the
      reactions between complex and branched oligosaccharides. The resultant allyl
      oligosaccharide was globally deprotected to obtain the heneicosasaccharyl
      arabinomannan as a propyl glycoside. In summary, heneicosasaccharyl mannose
      capped arabinomannan synthesis was achieved in 56 steps with 0.016% overall
      yield.

PMID- 28451322
TI  - Sonogashira diversification of unprotected halotryptophans, halotryptophan
      containing tripeptides; and generation of a new to nature bromo-natural product
      and its diversification in water.
AB  - The blending together of synthetic chemistry with natural product biosynthesis
      represents a potentially powerful approach to synthesis; to enable this, further
      synthetic tools and methodologies are needed. To this end, we have explored the
      first Sonogashira cross-coupling to halotryptophans in water. Broad reaction
      scope is demonstrated and we have explored the limits of the scope of the
      reaction. We have demonstrated this methodology to work excellently in the
      modification of model tripeptides. Furthermore, through precursor directed
      biosynthesis, we have generated for the first time a new to nature brominated
      natural product bromo-cystargamide, and demonstrated the applicability of our
      reaction conditions to modify this novel metabolite.

PMID- 28451323
TI  - AIEgens for dark through-bond energy transfer: design, synthesis, theoretical
      study and application in ratiometric Hg2+ sensing.
AB  - A novel dark through-bond energy transfer (DTBET) strategy is proposed and
      applied as the design strategy to develop ratiometric Hg2+ sensors with high
      performance. Tetraphenylethene (TPE) derivatives with aggregation-induced
      emission (AIE) characteristics are selected as dark donors to eliminate emission
      leakage from the donors. The TBET mechanism has been adopted since it experiences
      less influence from spectral overlapping than Forster resonance energy transfer
      (FRET), making it more flexible for developing cassettes with large pseudo-Stokes
      shifts. In this work, energy transfer from the TPE derivatives (dark donor) to a
      rhodamine moiety (acceptor) was illustrated through photophysical spectroscopic
      studies and the energy transfer efficiency (ETE) was found to be up to 99%. In
      the solution state, no emission from the donors was observed and large pseudo
      Stokes shifts were achieved (>280 nm), which are beneficial for biological
      imaging. Theoretical calculations were performed to gain a deeper mechanistic
      insight into the DTBET process and the structure-property relationship of the
      DTBET cassettes. Ratiometric Hg2+ sensors were rationally constructed based on
      the DTBET mechanism by taking advantage of the intense emission of TPE
      aggregates. The Hg2+ sensors exhibited well resolved emission peaks. >6000-fold
      ratiometric fluorescent enhancement is also achieved and the detection limit was
      found to be as low as 0.3 ppb. This newly proposed DTBET mechanism could be used
      to develop novel ratiometric sensors for various analytes and AIEgens with DTBET
      characteristics will have great potential in various areas including light
      harvesting materials, environmental science, chemical sensing, biological imaging
      and diagnostics.

PMID- 28451324
TI  - Enabling the controlled assembly of antibody conjugates with a loading of two
      modules without antibody engineering.
AB  - The generation of antibody conjugates with a loading of two modules is desirable
      for a host of reasons. Whilst certain antibody engineering approaches have been
      useful in the preparation of such constructs, a reliable method based on a native
      antibody scaffold without the use of enzymes or harsh oxidative conditions has
      hitherto not been achieved. The use of native antibodies has several advantages
      in terms of cost, practicality, accessibility, time and overall efficiency.
      Herein we present a novel, reliable method of furnishing antibody conjugates with
      a loading of two modules starting from a native antibody scaffold.

PMID- 28451325
TI  - Protein structure refinement using a quantum mechanics-based chemical shielding
      predictor.
AB  - The accurate prediction of protein chemical shifts using a quantum mechanics (QM)
      based method has been the subject of intense research for more than 20 years but
      so far empirical methods for chemical shift prediction have proven more accurate.
      In this paper we show that a QM-based predictor of a protein backbone and CB
      chemical shifts (ProCS15, PeerJ, 2016, 3, e1344) is of comparable accuracy to
      empirical chemical shift predictors after chemical shift-based structural
      refinement that removes small structural errors. We present a method by which
      quantum chemistry based predictions of isotropic chemical shielding values
      (ProCS15) can be used to refine protein structures using Markov Chain Monte Carlo
      (MCMC) simulations, relating the chemical shielding values to the experimental
      chemical shifts probabilistically. Two kinds of MCMC structural refinement
      simulations were performed using force field geometry optimized X-ray structures
      as starting points: simulated annealing of the starting structure and constant
      temperature MCMC simulation followed by simulated annealing of a representative
      ensemble structure. Annealing of the CHARMM structure changes the CA-RMSD by an
      average of 0.4 A but lowers the chemical shift RMSD by 1.0 and 0.7 ppm for CA and
      N. Conformational averaging has a relatively small effect (0.1-0.2 ppm) on the
      overall agreement with carbon chemical shifts but lowers the error for nitrogen
      chemical shifts by 0.4 ppm. If an amino acid specific offset is included the
      ProCS15 predicted chemical shifts have RMSD values relative to experiments that
      are comparable to popular empirical chemical shift predictors. The annealed
      representative ensemble structures differ in CA-RMSD relative to the initial
      structures by an average of 2.0 A, with >2.0 A difference for six proteins. In
      four of the cases, the largest structural differences arise in structurally
      flexible regions of the protein as determined by NMR, and in the remaining two
      cases, the large structural change may be due to force field deficiencies. The
      overall accuracy of the empirical methods are slightly improved by annealing the
      CHARMM structure with ProCS15, which may suggest that the minor structural
      changes introduced by ProCS15-based annealing improves the accuracy of the
      protein structures. Having established that QM-based chemical shift prediction
      can deliver the same accuracy as empirical shift predictors we hope this can help
      increase the accuracy of related approaches such as QM/MM or linear scaling
      approaches or interpreting protein structural dynamics from QM-derived chemical
      shift.

PMID- 28451326
TI  - Antimony-ligated dysprosium single-molecule magnets as catalysts for stibine
      dehydrocoupling.
AB  - Single-molecule magnets (SMMs) are coordination compounds that exhibit magnetic
      bistability below a characteristic blocking temperature. Research in this field
      continues to evolve from its fundamental foundations towards applications of SMMs
      in information storage and spintronic devices. Synthetic chemistry plays a
      crucial role in targeting the properties that could ultimately produce SMMs with
      technological potential. The ligands in SMMs are invariably based on non-metals;
      we now report a series of dysprosium SMMs (in addition to their magnetically
      dilute analogues embedded in yttrium matrices) that contain ligands with the
      metalloid element antimony as the donor atom, i.e. [(eta5-Cp'2Dy){MU-Sb(H)Mes}]3
      (1-Dy) and [(eta5-Cp'2Dy)3{MU-(SbMes)3Sb}] (2-Dy), which contain the stibinide
      ligand [Mes(H)Sb]- and the unusual Zintl-like ligand [Sb4Mes3]3-, respectively
      (Cp' = methylcyclopentadienyl; Mes = mesityl). The zero-field anisotropy barriers
      in 1-Dy and 2-Dy are Ueff = 345 cm-1 and 270 cm-1, respectively. Stabilization of
      the antimony-ligated SMMs is contingent upon careful control of reaction time and
      temperature. With longer reaction times and higher temperatures, the stibine pro
      ligands are catalytically dehydrocoupled by the rare-earth precursor complexes.
      NMR spectroscopic studies of the yttrium-catalysed dehydrocoupling reactions
      reveal that 1-Y and 2-Y are formed during the catalytic cycle. By implication, 1
      Dy and 2-Dy should also be catalytic intermediates, hence the nature of these
      complexes as SMMs in the solid-state and as catalysts in solution introduces a
      strategy whereby new molecular magnets can be identified by intercepting species
      formed during catalytic reactions.

PMID- 28451327
TI  - Iron catalyzed methylation and ethylation of vinyl arenes.
AB  - Short alkyl chain Heck (type) reactions, especially methyl Heck reactions, are a
      difficult aspect of the alkyl Heck reaction. To provide a solution to this
      problem, iron-catalyzed methyl, ethyl and propyl Heck reactions were developed
      using readily available alkyl peroxides as alkyl sources. The reaction conditions
      were mild, clean, and easy to handle. No additive was needed, and no hazardous
      waste was generated. The products were obtained in up to 99% yield of one isomer
      for most situations. This reaction works for many types of olefin and tolerates a
      variety of functional groups. Several late-stage functionalizations of natural
      products and drug molecules were conducted to demonstrate the synthetic
      applications of this reaction.

PMID- 28451328
TI  - Tuning excited-state-intramolecular-proton-transfer (ESIPT) process and emission
      by cocrystal formation: a combined experimental and theoretical study.
AB  - The formation of two-component molecular cocrystals can lead to the tunable
      excited state intramolecular proton transfer (ESIPT) process and emission, as
      first confirmed by both experimental and computational studies.

PMID- 28451330
TI  - Why conclusions from platinum model surfaces do not necessarily lead to enhanced
      nanoparticle catalysts for the oxygen reduction reaction.
AB  - Experiments on model surfaces commonly help in identifying the structural
      sensitivity of catalytic reactions. Nevertheless, their conclusions do not
      frequently lead to devising superior "real-world" catalysts. For instance, this
      is true for single-crystal platinum electrodes and the oxygen reduction reaction
      (ORR), an important reaction for sustainable energy conversion. Pt(111) is
      substantially enhanced by steps, reaching a maximum at short terrace lengths of 3
      4 atoms. Conversely, regular platinum nanoparticles with similar undercoordinated
      defects are less active than Pt(111) and their activity increases alongside the
      terrace-to-defect ratio. We show here that a model to design ORR active sites on
      extended surfaces can also be used to solve this apparent contradiction and
      provide accurate design rules for nanoparticles. Essentially, only surfaces and
      nanostructures with concave defects can surpass the activity of Pt(111), whereas
      convex defects are inactive. Importantly, only the latter are present in regular
      nanoparticles, which is why we design various concave nanoparticles with high
      activities.

PMID- 28451329
TI  - Macrocyclic shape-persistency of cyclo[6]aramide results in enhanced multipoint
      recognition for the highly efficient template-directed synthesis of rotaxanes.
AB  - Examples of using two-dimensional shape-persistent macrocycles, i.e. those having
      noncollapsible and geometrically well-defined skeletons, for constructing
      mechanically interlocked molecules are scarce, which contrasts the many
      applications of these macrocycles in molecular recognition and functional self
      assembly. Herein, we report the crucial role played by macrocyclic shape
      persistency in enhancing multipoint recognition for the highly efficient template
      directed synthesis of rotaxanes. Cyclo[6]aramides, with a near-planar
      conformation, are found to act as powerful hosts that bind bipyridinium salts
      with high affinities. This unique recognition module, composed of two macrocyclic
      molecules with one bipyridinium ion thread through the cavity, is observed both
      in the solid state and in solution, with unusually high binding constants ranging
      from ~1013 M-2 to ~1015 M-2 in acetone. The high efficacy of this recognition
      motif is embodied by the formation of compact [3]rotaxanes in excellent yields
      based on either a "click-capping" (91%) or "facile one-pot" (85%) approach,
      underscoring the great advantage of using H-bonded aromatic amide macrocycles for
      the highly efficient template-directed synthesis of mechanically interlocked
      structures. Furthermore, three cyclo[6]aramides bearing different peripheral
      chains 1-3 demonstrate high specificity in the synthesis of a [3]rotaxane from 1
      and 2, and a [2]rotaxane from 3via a "facile one-pot" approach, in each case as
      the only isolated product. Analysis of the crystal structure of the [3]rotaxane
      reveals a highly compact binding mode that would be difficult to access using
      other macrocycles with a flexible backbone. Leveraging this unique recognition
      motif, resulting from the shape-persistency of these oligoamide macrocycles, in
      the template-directed synthesis of compact rotaxanes may open up new
      opportunities for the development of higher order interlocked molecules and
      artificial molecular machines.

PMID- 28451331
TI  - Switchable slow relaxation of magnetization in the native low temperature phase
      of a cooperative spin-crossover compound.
AB  - The implementation of single-molecule magnet properties in spin crossover
      materials is sought as a unique source of magnetic multistability at the
      molecular level. Examples however remain extremely scarce, in part due to the
      diamagnetic state of most Fe(ii) spin crossover materials at low temperatures. We
      have studied the complex [Fe(mtz)6](CF3SO3)2 (mtz = 1-methyltetrazole) as a
      tantalizing candidate of such coexistence, due to its known partial spin
      crossover and therefore paramagnetic native low temperature phase. The single
      crystal structures of [Fe(mtz)6](CF3SO3)2 reported here allow rationalizing its
      peculiar cooperative spin-crossover behavior. Importantly, the high-spin Fe
      crystallographic sites at low temperature exhibit a high symmetry with a local
      trigonal distortion, usually source of magnetic anisotropy. The analysis of
      equilibrium magnetic properties confirm the presence of a significant magnetic
      anisotropy at the Fe(ii) high spin sites in the high symmetry low temperature
      phase. This results in field-induced slow relaxation of their magnetization which
      is dominated at low temperature by tunneling and direct processes and is strongly
      enhanced above 3 K by Raman and Orbach processes. Unprecedentedly, these single
      molecule magnet properties are observed in the native ground state of a spin
      crossover material and efficiently and reversibly switched OFF through visible
      light irradiation.

PMID- 28451332
TI  - Synthesis of rhamnosylated arginine glycopeptides and determination of the
      glycosidic linkage in bacterial elongation factor P.
AB  - A new class of N-linked protein glycosylation - arginine rhamnosylation - has
      recently been discovered as a critical modification for the function of bacterial
      elongation factor P (EF-P). Herein, we describe the synthesis of suitably
      protected alpha- and beta-rhamnosylated arginine amino acid "cassettes" that can
      be directly installed into rhamnosylated peptides. Preparation of a proteolytic
      fragment of Pseudomonas aeruginosa EF-P bearing both alpha- and beta
      rhamnosylated arginine enabled the unequivocal determination of the native
      glycosidic linkage to be alpha through 2D NMR and nano-UHPLC-tandem mass
      spectrometry studies.

PMID- 28451333
TI  - Catalytic activity of catalase-silica nanoparticle hybrids: from ensemble to
      individual entity activity.
AB  - We demonstrate the electrochemical detection and characterization of individual
      nanoparticle-enzyme hybrids. Silica nanoparticles were functionalized with
      catalase enzyme and investigated spectroscopically and electrochemically. The
      catalytic activity of the hybrids towards hydrogen peroxide decomposition was
      comparable to the activity of a freely diffusing enzyme in solution, exhibiting a
      Michaelis-Menten constant of KM = 74 mM and a turnover number of kcat = 8 * 107 s
      1 per NP. The fast turnover number of the hybrid further enabled the
      electrochemical detection of individual nanoparticle-enzyme hybrid via a novel
      method: the hydrogen peroxide substrate was generated at a microelectrode which
      enabled enzymatic activity exclusively within the diffusion layer of the
      electrode. The method is the first electrochemical approach for measuring hybrid
      nanoparticles, at the single entity level.

PMID- 28451334
TI  - Zirconium tetraazamacrocycle complexes display extraordinary stability and
      provide a new strategy for zirconium-89-based radiopharmaceutical development.
AB  - We report our initial investigations into the use of tetraazamacrocycles as
      zirconium-89 chelators. We describe the synthesis and complete characterization
      of several Zr tetraazamacrocycle complexes, and definitively describe the first
      crystal structure of zirconium 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (Zr-DOTA) using single crystal X-ray diffraction analysis. After
      evaluating several radioactive analogs, we found that 89Zr-DOTA is superior to
      89Zr-DFO, the only 89Zr-complex to be used clinically in 89Zr-radiopharmaceutical
      applications. Finally, we provide a rationale for the unanticipated and
      extraordinary stability of these complexes in vitro and in vivo. These results
      may inform the development of safer and more robust immuno-PET agents for
      precision medicine applications.

PMID- 28451335
TI  - Characterizing aliphatic moieties in hydrocarbons with atomic force microscopy.
AB  - We designed and studied hydrocarbon model compounds by high-resolution noncontact
      atomic force microscopy. In addition to planar polycyclic aromatic moieties,
      these novel model compounds feature linear alkyl and cycloaliphatic motifs that
      exist in most hydrocarbon resources - particularly in petroleum asphaltenes and
      other petroleum fractions - or in lipids in biological samples. We demonstrate
      successful intact deposition by sublimation of the alkyl-aromatics, and
      differentiate aliphatic moieties from their aromatic counterparts which were
      generated from the former by atomic manipulation. The characterization by AFM in
      combination with atomic manipulation provides clear fingerprints of the aromatic
      and aliphatic moieties that will facilitate their assignment in a priori unknown
      samples.

PMID- 28451337
TI  - One-step electric-field driven methane and formaldehyde synthesis from liquid
      methanol.
AB  - The reaction pathways connecting methanol to methane and formaldehyde are among
      the most emblematic in chemistry because of their outstanding interest in the
      fields of energy, synthesis, and bio- and geo-chemistry. Despite of its
      fundamental nature, the one-pot synthesis of formaldehyde and methane stemming
      from methanol has never been reported before. Here we present a study, based on
      ab initio molecular dynamics and free-energy methods, in which the simultaneous
      oxidation and reduction (i.e., the disproportionation) of liquid methanol into
      methane and formaldehyde has been achieved at ambient temperature through the
      application of a static electric field. Because strong electric fields can be
      generated in the proximity of field emitter tips, this finding shows that the
      challenge of experimentally disproportionating methanol into formaldehyde and
      methane could be attempted. We show that the methanol "solvent" molecules play a
      major role in this process and that the chemical pathway connecting methanol to
      the detected products in the bulk liquid phase is very different from its
      reproduced gas-phase counterpart. Finally, we demonstrate that switching on an
      external electric field drastically modifies the reaction network of methanol,
      lowering some activation barriers, stabilizing the methane and formaldehyde
      products, and opening otherwise difficult-to-achieve chemical routes.

PMID- 28451336
TI  - Exploring secondary-sphere interactions in Fe-N x H y complexes relevant to N2
      fixation.
AB  - Hydrogen bonding and other types of secondary-sphere interactions are ubiquitous
      in metalloenzyme active sites and are critical to the transformations they
      mediate. Exploiting secondary sphere interactions in synthetic catalysts to study
      the role(s) they might play in biological systems, and to develop increasingly
      efficient catalysts, is an important challenge. Whereas model studies in this
      broad context are increasingly abundant, as yet there has been relatively little
      progress in the area of synthetic catalysts for nitrogen fixation that
      incorporate secondary sphere design elements. Herein we present our first study
      of Fe-N x H y complexes supported by new tris(phosphine)silyl ligands,
      abbreviated as [SiPNMe3] and [SiPiPr2PNMe], that incorporate remote tertiary
      amine hydrogen-bond acceptors within a tertiary phosphine/amine 6-membered ring.
      These remote amine sites facilitate hydrogen-bonding interactions via a boat
      conformation of the 6-membered ring when certain nitrogenous substrates (e.g.,
      NH3 and N2H4) are coordinated to the apical site of a trigonal bipyramidal iron
      complex, and adopt a chair conformation when no H-bonding is possible (e.g., N2).
      Countercation binding at the cyclic amine is also observed for anionic {Fe-N2}-
      complexes. Reactivity studies in the presence of proton/electron sources show
      that the incorporated amine functionality leads to rapid generation of
      catalytically inactive Fe-H species, thereby substantiating a hydride termination
      pathway that we have previously proposed deactivates catalysts of the type
      [EPR3]FeN2 (E = Si, C).

PMID- 28451338
TI  - Reactivity of a coordinated inorganic acetylene unit, HBNH, and the azidoborane
      cation [HB(N3)].
AB  - A donor-acceptor complex of HBNH was prepared via thermolysis of a carbene
      stabilized azidoborane. The reactivity of the fundamentally important HBNH unit
      (inorganic alkyne analogue) was explored in detail, including attempts to convert
      this species and related hydrido(azido)borane cations into molecular complexes of
      BN. This work provides added impetus for the development of molecular precursors
      that can release bulk boron nitride (a desirable insulator and thermal conductor)
      under mild conditions, and from solution.

PMID- 28451339
TI  - Surface engineering to achieve organic ternary memory with a high device yield
      and improved performance.
AB  - Squaraine molecules deposited on indium tin oxide (ITO) substrates modified with
      phosphonic acids crystalize more orderly than do those on untreated ITO. The as
      fabricated electro-resistive memories show the highest ternary device yield
      observed to date (82%), a narrower switching voltage distribution, and better
      retention as well as resistance uniformity.

PMID- 28451340
TI  - The interplay between fluorescence and phosphorescence with luminescent gold(i)
      and gold(iii) complexes bearing heterocyclic arylacetylide ligands.
AB  - The photophysical properties of a series of gold(i) [LAu(C
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      PCy3 (1a-4a), RNC (5a), NHC (6a)) and gold(iii) complexes [Au(C^N^C)(CCR)] (1b
      4b) bearing heterocyclic arylacetylide ligands with narrow band-gap are compared.
      The luminescence of both series are derived from an intraligand transition
      localized on the arylacetylide ligand (pipi*(CCR)) but 1a-3a displayed prompt
      fluorescence (tauPF = 2.7-12.0 ns) while 1b-3b showed mainly phosphorescence
      (tauPh = 104-205 MUs). The experimentally determined intersystem crossing (ISC)
      rate constants (kISC) are on the order of 106 to 108 s-1 for the gold(i) series
      (1a-3a) but 1010 to 1011 s-1 for the gold(iii) analogues (1b-3b). DFT/TDDFT
      calculations have been performed to help understand the difference in the kISC
      between the two series of complexes. Owing to the different oxidation states of
      the gold ion, the Au(i) complexes have linear coordination geometry while the
      Au(iii) complexes are square planar. It was found from DFT/TDDFT calculations
      that due to this difference in coordination geometries, the energy gap between
      the singlet and triplet excited states (DeltaEST) with effective spin-orbit
      coupling (SOC) for Au(i) systems is much larger than that for the Au(iii)
      counterparts, thus resulting in the poor ISC efficiency for the former. Time
      resolved spectroscopies revealed a minor contribution (<2.9%) of a long-lived
      delayed fluorescence (DF) (tauDF = 4.6-12.5 MUs) to the total fluorescence in 1a
      3a. Attempts have been made to elucidate the mechanism for the origins of the DF:
      the dependence of the DF intensity with the power of excitation light reveals
      that triplet-triplet annihilation (TTA) is the most probable mechanism for the DF
      of 1a while germinate electron-hole pair (GP) recombination accounts for the DF
      of 2a in 77 K glassy solution (MeOH/EtOH = 4 : 1). Both 4a and 4b contain a
      BODIPY moiety at the acetylide ligand and display only 1IL(pipi*) fluorescence
      with negligible phosphorescence being observed. Computational analyses attributed
      this observation to the lack of low-lying triplet excited states that could have
      effective SOC with the S1 excited state.

PMID- 28451341
TI  - Rectification of current responds to incorporation of fullerenes into mixed
      monolayers of alkanethiolates in tunneling junctions.
AB  - This paper describes the rectification of current through molecular junctions
      comprising self-assembled monolayers of decanethiolate through the incorporation
      of C60 fullerene moieties bearing undecanethiol groups in junctions using
      eutectic Ga-In (EGaIn) and Au conducting probe AFM (CP-AFM) top-contacts. The
      degree of rectification increases with increasing exposure of the decanethiolate
      monolayers to the fullerene moieties, going through a maximum after 24 h. We
      ascribe this observation to the resulting mixed-monolayer achieving an optimal
      packing density of fullerene cages sitting above the alkane monolayer. Thus, the
      degree of rectification is controlled by the amount of fullerene present in the
      mixed-monolayer. The voltage dependence of R varies with the composition of the
      top-contact and the force applied to the junction and the energy of the lowest
      unoccupied pi-state determined from photoelectron spectroscopy is consistent with
      the direction of rectification. The maximum value of rectification R = |J(+)/J(
      )| = 940 at +/-1 V or 617 at +/-0.95 V is in agreement with previous studies on
      pure monolayers relating the degree of rectification to the volume of the head
      group on which the frontier orbitals are localized.

PMID- 28451342
TI  - Effect of ring rotation upon gas adsorption in SIFSIX-3-M (M = Fe, Ni) pillared
      square grid networks.
AB  - Dynamic and flexible metal-organic frameworks (MOFs) that respond to external
      stimuli, such as stress, light, heat, and the presence of guest molecules, hold
      promise for applications in chemical sensing, drug delivery, gas separations, and
      catalysis. A greater understanding of the relationship between flexible
      constituents in MOFs and gas adsorption may enable the rational design of MOFs
      with dynamic moieties and stimuli-responsive behavior. Here, we detail the effect
      of subtle structural changes upon the gas sorption behavior of two "SIFSIX"
      pillared square grid frameworks, namely SIFSIX-3-M (M = Ni, Fe). We observe a
      pronounced inflection in the Xe adsorption isotherm in the Ni variant. With
      evidence from X-ray diffraction studies, density functional theory, and molecular
      simulations, we attribute the inflection to a disordered to ordered transition of
      the rotational configurations of the pyrazine rings induced by sorbate-sorbent
      interactions. We also address the effect of cage size, temperature, and sorbate
      on the guest-induced ring rotation and the adsorption isotherms. The absence of
      an inflection in the Xe adsorption isotherm in SIFSIX-3-Fe and in the Kr, N2, and
      CO2 adsorption isotherms in SIFSIX-3-Ni suggest that the inflection is highly
      sensitive to the match between the size of the cage and the guest molecule.

PMID- 28451343
TI  - Light responsive metal-organic frameworks as controllable CO-releasing cell
      culture substrates.
AB  - A new carbon monoxide (CO)-releasing material has been developed by embedding a
      manganese carbonyl complex, MnBr(bpydc)(CO)3 (bpydc = 5,5'-dicarboxylate-2,2'
      bipyridine) into a highly robust Zr(iv)-based metal-organic framework (MOF).
      Efficient and controllable CO-release was achieved under exposure to low
      intensity visible light. Size-controllable nanocrystals of the photoactive MOF
      were obtained and their CO-releasing properties were correlated with their
      crystal sizes. The photoactive crystals were processed into cellular substrates
      with a biocompatible polymer matrix, and the light-induced delivery of CO and its
      subsequent cellular uptake were monitored using a fluorescent CO-probe. The
      results discussed here demonstrate a new opportunity to use MOFs as
      macromolecular scaffolds towards CO-releasing materials and the advantage of MOFs
      for high CO payloads, which is essential in future therapeutic applications.

PMID- 28451344
TI  - Development of a facile antibody-drug conjugate platform for increased stability
      and homogeneity.
AB  - Despite the advances in the design of antibody-drug conjugates (ADCs), the search
      is still ongoing for novel approaches that lead to increased stability and
      homogeneity of the ADCs. We report, for the first time, an ADC platform
      technology using a platinum(ii)-based linker that can re-bridge the inter-chain
      cysteines in the antibody, post-reduction. The strong platinum-sulfur interaction
      improves the stability of the ADC when compared with a standard maleimide-linked
      ADC thereby reducing the linker-drug exchange with albumin significantly.
      Moreover, due to the precise conserved locations of cysteines, both homogeneity
      and site-specificity are simultaneously achieved. Additionally, we demonstrate
      that our ADCs exhibit increased anticancer efficacy in vitro and in vivo. The Pt
      based ADCs can emerge as a simple and exciting proposition to address the
      limitations of the current ADC linker technologies.

PMID- 28451345
TI  - Protein-based fluorescent nanoparticles for super-resolution STED imaging of live
      cells.
AB  - Development of nanoparticles for super-resolution imaging (sriNPs) can greatly
      enrich the toolbox of robust optical probes for biological studies. Moreover,
      sriNPs enable us to monitor the behavior of engineered nanomaterials in complex
      biological environments with high spatial resolution, which is important for
      advancing our understanding of nano-bio interactions. Up to now, reports on
      sriNPs have been scarce. In this work, we report a facile strategy to prepare
      protein-based fluorescent NPs that can be utilized as probes in super-resolution
      microscopy. The method is simple and straightforward, and easily extendible to
      other types of fluorophores. By using Atto647N-transferrin NPs as an example, we
      have achieved a roughly four-fold resolution improvement by using STED nanoscopy.
      These protein-based sriNPs possess excellent biocompatibility, good colloidal
      stability and photostability, making them attractive candidates for biological
      studies. Moreover, STED nanoscopy enables the precise imaging of NP structures in
      living cells, and revealed the co-existence of multiple NPs within one endosomal
      vesicle.

PMID- 28451346
TI  - Organocatalytic activation of isocyanides: N-heterocyclic carbene-catalyzed
      enaminone synthesis from ketones.
AB  - The first example of the use of an N-heterocyclic carbene (NHC) as an
      organocatalyst for the activation of isocyanides was demonstrated. On the basis
      of previous reports on the interaction between NHCs and isocyanides, we developed
      a catalytic cycle involving transient imidoyl intermediate. The reaction of
      ketones with isocyanides produced the corresponding enaminones with high
      efficiency. Control experiments suggested a novel role for the carbene in the
      activation of isocyanides, and a proton transfer process was found to be crucial
      for the generation of two activated species in the catalytic cycle. Various
      enaminones, some of which are not easily accessible by other methods, were
      synthesized in excellent yields. This study clearly demonstrates the potential of
      the nucleophilic activation of isocyanides in the expansion of their reactivity
      scope.

PMID- 28451347
TI  - Contact electrification induced interfacial reactions and direct electrochemical
      nanoimprint lithography in n-type gallium arsenate wafer.
AB  - Although metal assisted chemical etching (MacEtch) has emerged as a versatile
      micro-nanofabrication method for semiconductors, the chemical mechanism remains
      ambiguous in terms of both thermodynamics and kinetics. Here we demonstrate an
      innovative phenomenon, i.e., the contact electrification between platinum (Pt)
      and an n-type gallium arsenide (100) wafer (n-GaAs) can induce interfacial redox
      reactions. Because of their different work functions, when the Pt electrode comes
      into contact with n-GaAs, electrons will move from n-GaAs to Pt and form a
      contact electric field at the Pt/n-GaAs junction until their electron Fermi
      levels (EF) become equal. In the presence of an electrolyte, the potential of the
      Pt/electrolyte interface will shift due to the contact electricity and induce the
      spontaneous reduction of MnO4- anions on the Pt surface. Because the equilibrium
      of contact electrification is disturbed, electrons will transfer from n-GaAs to
      Pt through the tunneling effect. Thus, the accumulated positive holes at the n
      GaAs/electrolyte interface make n-GaAs dissolve anodically along the Pt/n
      GaAs/electrolyte 3-phase interface. Based on this principle, we developed a
      direct electrochemical nanoimprint lithography method applicable to crystalline
      semiconductors.

PMID- 28451349
TI  - Pairwise hydrogen addition in the selective semihydrogenation of alkynes on
      silica-supported Cu catalysts.
AB  - Mechanistic insight into the semihydrogenation of 1-butyne and 2-butyne on Cu
      nanoparticles supported on partially dehydroxylated silica (Cu/SiO2-700) was
      obtained using parahydrogen. Hydrogenation of 1-butyne over Cu/SiO2-700 yielded 1
      butene with >=97% selectivity. The surface modification of this catalyst with
      tricyclohexylphosphine (PCy3) increased the selectivity to 1-butene up to nearly
      100%, although at the expense of reduced catalytic activity. Similar trends were
      observed in the hydrogenation of 2-butyne, where Cu/SiO2-700 provided a
      selectivity to 2-butene in the range of 72-100% depending on the reaction
      conditions, while the catalyst modified with PCy3 again demonstrated nearly 100%
      selectivity. Parahydrogen-induced polarization effects observed in hydrogenation
      reactions catalyzed by copper-based catalysts demonstrate the viability of
      pairwise hydrogen addition over these catalysts. Contribution of pairwise
      hydrogen addition to 1-butyne was estimated to be at least 0.2-0.6% for
      unmodified Cu/SiO2-700 and >=2.7% for Cu/SiO2-700 modified with PCy3,
      highlighting the effect of surface modification with the tricyclohexylphosphine
      ligand.

PMID- 28451348
TI  - Differences between the elimination of early and late transition metals: DFT
      mechanistic insights into the titanium-catalyzed synthesis of pyrroles from
      alkynes and diazenes.
AB  - Early transition metals (TMs), such as titanium, generally resist undergoing
      reductive elimination to form C-X bonds due to their weak electronegativity. By
      analyzing the mechanism of the titanium-catalyzed synthesis of pyrroles from
      alkynes and diazenes, the present study revealed that titanium is able to promote
      C-N bond formation via an unconventional elimination pathway, passing through a
      comparatively stable masked TiII complex (i.e., IM4) rather than pyrrole
      directly. The formation of IM4 originates from the bilateral donation and back
      donation between Ti and the pyrrole ligand. Formally, it could be considered that
      the two electrons resulting from the unconventional reductive elimination are
      temporarily buffered by back-donation to a symmetry-allowed unoccupied pi-orbital
      of the pyrrole ring in IM4 rather than becoming a lone pair on a Ti center as
      adopted in the catalysis of late TMs. Because of its stability, IM4 requires
      additional oxidation by diazene to liberate pyrrole. The triplet counterpart
      (IM4T ) of IM4 is more stable than IM4, but the elimination is unlikely to reach
      IM4T , because the process is spin-forbidden and the spin-orbit coupling is weak.
      Alternatively, one may consider the forming pyrrole in IM4 as a redox-active
      ligand, reserving the two electrons resulting from the formal reductive
      elimination and then releasing the electrons when IM4 is oxidized by diazene.
      These insights allow us to propose the conditions for early TMs to undergo a
      similar elimination, whereby the forming product will have symmetry-allowed
      frontier molecular orbitals to form donation and back-donation bonding with a TM
      center and a substrate possessing a comparatively strong oxidizing ability to
      oxidize an IM4-like intermediate for product release. These insights may provide
      another way of constructing C-X bonds through a similar reductive elimination
      pathway, using early TM catalysts.

PMID- 28451350
TI  - Cobalt catalyzed carbonylation of unactivated C(sp3)-H bonds.
AB  - A general efficient regioselective cobalt catalyzed carbonylation of unactivated
      C(sp3)-H bonds of aliphatic amides was demonstrated using atmospheric (1-2 atm)
      carbon monoxide as a C1 source. This straightforward approach provides access to
      alpha-spiral succinimide regioselectively in a good yield. Cobalt catalyzed sp3 C
      H bond carbonylation is reported for the first time including the
      functionalization of (beta)-C-H bonds of alpha-1 degrees , 2 degrees , 3 degrees 
      carbons and even internal (beta)-C-H bonds. Our initial mechanistic investigation
      reveals that the C-H activation step is irreversible and will possibly be the
      rate determining step.

PMID- 28451351
TI  - A new class of Cu/ZnO catalysts derived from zincian georgeite precursors
      prepared by co-precipitation.
AB  - Zincian georgeite, an amorphous copper-zinc hydroxycarbonate, has been prepared
      by co-precipitation using acetate salts and ammonium carbonate. Incorporation of
      zinc into the georgeite phase and mild ageing conditions inhibits crystallisation
      into zincian malachite or aurichalcite. This zincian georgeite precursor was used
      to prepare a Cu/ZnO catalyst, which exhibits a superior performance to a zincian
      malachite derived catalyst for methanol synthesis and the low temperature water
      gas shift (LTS) reaction. Furthermore, the enhanced LTS activity and stability in
      comparison to that of a commercial Cu/ZnO/Al2O3 catalyst, indicates that the
      addition of alumina as a stabiliser may not be required for the zincian georgeite
      derived Cu/ZnO catalyst. The enhanced performance is partly attributed to the
      exclusion of alkali metals from the synthesis procedure, which are known to act
      as catalyst poisons. The effect of residual sodium on the microstructural
      properties of the catalyst precursor was investigated further from preparations
      using sodium carbonate.

PMID- 28451352
TI  - CO/CO and NO/NO coupling at a hidden frustrated Lewis pair template.
AB  - N-Allyltetramethylpiperidine is readily isomerized to the corresponding enamine
      by treatment with catalytic amounts of B(C6F5)3. It adds HB(C6F5)2 at the
      nucleophilic enamine carbon atom to form a C/B Lewis adduct. This reacts with two
      molar equivalents of carbon monoxide by selective head to tail coupling to give a
      five-membered C2O2B heterocycle. In contrast the enamine/HB(C6F5)2 Lewis pair
      reacts with two molar equiv. of nitric oxide by head to head coupling. This
      reaction probably proceeds via equilibrium with the corresponding vicinal N/B
      Lewis pair. Most products were characterized by X-ray diffraction.

PMID- 28451353
TI  - Highly specific noninvasive photoacoustic and positron emission tomography of
      brain plaque with functionalized croconium dye labeled by a radiotracer.
AB  - Highly-efficient targeting probes are desirable for disease diagnosis and
      functional imaging. However, most of the current near-infrared (NIR) probes
      suffer from low signal conversion, insufficient photostability, poor probe
      specificity, and limited functions. Herein, an NIR ultrahigh absorbing croconium
      dye for amyloid (CDA) was designed and synthesized to specifically bind to
      cerebrovascular amyloid without antibody linkage. This unique CDA is able to
      strongly bind the hydrophobic channels of amyloid beta (Abeta) fiber with a very
      strong binding energy of -9.3 kcal mol-1. Our experimental results demonstrate
      that the amphipathic dye with an intense absorption peak at 800 nm generated a
      significant local temperature surge under low-power laser irradiation. Compared
      with representative prominent indocyanine green, Prussian blue, and gold
      nanorods, this probe can produce the strongest photoacoustic signal based on the
      same mass concentration. Labeled with radioactive 18F, this multifunctional probe
      allowed for the ultrasensitive photoacoustic tomography (PAT)/positron emission
      tomography (PET)/fluorescence imaging of Abeta plaques in the brain cortex.
      Featured with high spatial resolution and optical specificity, PAT was
      intrinsically suitable for imaging pathological sites on cortical vessels,
      whereas PET revealed whole-body anatomy with quantitative biodistribution
      information. Our study shows that a CDA-based functionalized dye aided with PAT
      and PET is capable of plaque diagnosis and localization.

PMID- 28451354
TI  - The development and mechanistic investigation of a palladium-catalyzed 1,3
      arylfluorination of chromenes.
AB  - A mild palladium-catalyzed ligand-controlled regioselective 1,3-arylfluorination
      of 2[H]-chromenes has been developed. The products with a syn-1,3 substitution
      pattern were obtained with high enantiomeric excess using a PyrOx ligand, wherein
      the utility of these pyranyl-fluorides was further demonstrated through their
      participation in a diastereoselective C-C bond forming reaction. Ligand dependent
      divergent formation of both the 1,3- and 1,2- alkene difunctionalization products
      was observed. The nature of this bifurcation was investigated through
      experimental studies in combination with computational and statistical analysis
      tools. Ultimately, the site selectivity was found to rely on ligand denticity and
      metal electrophilicity, the electronics of the boronic acid, and the donor
      ability of the directing group in the substrate.

PMID- 28451355
TI  - Selective uni- and bidirectional homologation of diborylmethane.
AB  - Diborylmethane can be homologated uni- and bidirectionally by using
      enantiomerically pure lithium-stabilized carbenoids to give 1,2- and 1,3
      bis(boronic esters), respectively, in good yield and with excellent levels of
      enantio- and diastereoselectivity. The high sensitivity of the transformation to
      steric hindrance enables the exclusive operation of either manifold, effected
      through the judicious choice of the type of carbenoid, which can be a sparteine
      ligated or a diamine-free lithiated benzoate/carbamate. The scope of the 1,2
      bis(boronic esters) so generated is complementary to that encompassed by the
      asymmetric diboration of alkenes, in that primary-secondary and primary-tertiary
      1,2-bis(boronic esters) can be prepared with equally high levels of selectivity
      and that functional groups, such as terminal alkynes and alkenes, are tolerated.
      Methods for forming C2-symmetric and non-symmetrical anti and syn 1,3-bis(boronic
      esters) are also described and represent a powerful route towards 1,3
      functionalized synthetic intermediates.

PMID- 28451356
TI  - Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4
      addition/Michael reaction through dynamic kinetic resolution under iminium
      catalysis. Development and mechanistic insights.
AB  - 2-Hydroxydihydropyran-5-ones behave as excellent polyfunctional reagents able to
      react with enals through oxa-Michael/Michael process cascade under the
      combination of iminium and enamine catalysis. These racemic hemiacetalic
      compounds are used as unconventional O-pronucleophiles in the initial oxa-Michael
      reaction, also leading to the formation of a single stereoisomer under a dynamic
      kinetic resolution (DKR) process. Importantly, by using beta-aryl or beta-alkyl
      substituted alpha,beta-unsaturated substrates as initial Michael acceptors either
      kinetically or thermodynamically controlled diastereoisomers were formed with
      high stereoselection through the careful selection of the reaction conditions.
      Finally, a complete experimental and computational study confirmed the initially
      proposed DKR process during the catalytic oxa-Michael/Michael cascade reaction
      and also explained the kinetic/thermodynamic pathway operating in each case.

PMID- 28451357
TI  - Mechanistic insights on the Pd-catalyzed addition of C-X bonds across alkynes - a
      combined experimental and computational study.
AB  - The Pd-catalyzed intramolecular addition of carbamoyl chlorides and aryl halides
      across alkynes is investigated by means of DFT calculations and mechanistic test
      experiments. The data suggest a mechanistic pathway that involves oxidative
      addition, alkyne insertion, cis -> trans isomerization and reductive elimination.
      Our data indicate that oxidative addition is the reactivity limiting step in the
      addition of aryl chlorides and bromides across alkynes. However, for the
      corresponding addition of carbamoyl chlorides, alkyne insertion is found to be
      limiting. Full energetic reaction pathways for the intramolecular additions
      across alkynes are presented herein and the role of ligands, alkyne substituents
      and tether moieties are discussed. Notably, the calculations could rationalize a
      pronounced effect of the alkyne substituent, which accounts for the exceptional
      reactivity of TIPS-substituted alkynes. In particular, the bulky silyl moiety is
      shown to significantly destabilize the formed Pd(ii)-intermediates, thus
      facilitating both cis -> trans isomerization and reductive elimination, which
      overall results in a flatter energetic landscape and a therefore increased
      catalytic efficiency.

PMID- 28451358
TI  - Synthetically controlling dendrimer flexibility improves delivery of large
      plasmid DNA.
AB  - Tools for editing the genome and epigenome have revolutionised the field of
      molecular biology and represent a new frontier in targeted therapeutic
      intervention. Although efficiencies and specificities of genome editing
      technologies have improved with the development of TALEs and CRISPR platforms,
      intracellular delivery of these larger constructs still remains a challenge using
      existing delivery agents. Viral vectors, including lentiviruses and adeno
      associated viruses, as well as some non-viral strategies, such as cationic
      polymers and liposomes, are limited by packaging capacity, poor delivery,
      toxicity, and immunogenicity. We report a highly controlled synthetic strategy to
      engineer a flexible dendritic polymer using click chemistry to overcome the
      aforementioned delivery challenges associated with genome engineering
      technologies. Using a systematic approach, we demonstrate that high transfection
      efficiencies and packaging capacity can be achieved using this non-viral delivery
      methodology to deliver zinc fingers, TALEs and CRISPR/dCas9 platforms.

PMID- 28451359
TI  - Zwitterionic amidinates as effective ligands for platinum nanoparticle
      hydrogenation catalysts.
AB  - Ligand control of metal nanoparticles (MNPs) is rapidly gaining importance as
      ligands can stabilize the MNPs and regulate their catalytic properties. Herein we
      report the first example of Pt NPs ligated by imidazolium-amidinate ligands that
      bind strongly through the amidinate anion to the platinum surface atoms. The
      binding was established by 15N NMR spectroscopy, a precedent for nitrogen ligands
      on MNPs, and XPS. Both monodentate and bidentate coordination modes were found.
      DFT showed a high bonding energy of up to -48 kcal mol-1 for bidentate bonding to
      two adjacent metal atoms, which decreased to -28 +/- 4 kcal mol-1 for monodentate
      bonding in the absence of impediments by other ligands. While the surface is
      densely covered with ligands, both IR and 13C MAS NMR spectra proved the
      adsorption of CO on the surface and thus the availability of sites for catalysis.
      A particle size dependent Knight shift was observed in the 13C MAS NMR spectra
      for the atoms that coordinate to the surface, but for small particles, ~1.2 nm,
      it almost vanished, as theory for MNPs predicts; this had not been experimentally
      verified before. The Pt NPs were found to be catalysts for the hydrogenation of
      ketones and a notable ligand effect was observed in the hydrogenation of electron
      poor carbonyl groups. The catalytic activity is influenced by remote electron
      donor/acceptor groups introduced in the aryl-N-substituents of the amidinates; p
      anisyl groups on the ligand gave catalysts several times faster the ligand
      containing p-chlorophenyl groups.

PMID- 28451360
TI  - Side-chain modulation of dithienofluorene-based copolymers to achieve high field
      effect mobilities.
AB  - A ladder-type dithieno[3,2-b:6,7-b']fluorene (DTF), where the central fluorene is
      fused with two outer thiophene rings at its 2,3- and 6,7-junctions, is developed.
      The pentacyclic DTF monomers were polymerized with dithienodiketopyrrolopyrrole
      (DPP) acceptors to afford three alternating donor-acceptor copolymers PDTFDPP16,
      PDTFDPP20, and PDTFDPP32 incorporating different aliphatic side chains (R1 group
      at DTF; R2 group at the DPP moieties). The side-chain variations in the polymers
      play a significant role in determining not only the intrinsic molecular
      properties but also the intermolecular packing. As evidenced by the 2-dimensional
      GIXS measurements, PDTFDPP16 with octyl (R1) and 2-ethylhexyl (R2) side chains
      tends to align in an edge-on pi-stacking orientation, whereas PDTFDPP20 using 2
      butyloctyl (R1) and 2-ethylhexyl (R2) adopts a predominately face-on orientation.
      PDTFDPP32 with the bulkiest 2-butyloctyl (R1) and 2-octyldodecyl (R2) side chains
      shows a less ordered amorphous character. The OFET device using PDTFDPP20 with a
      face-on orientation determined by GIXS measurements achieved a high hole-mobility
      of up to 5 cm2 V-1 s-1. The high rigidity and coplanarity of the DTF motifs play
      an important role in facilitating intramolecular 1-dimensional charge transport
      within the polymer backbones. The implementation of main-chain coplanarity and
      side-chain engineering strategies in this research provides in-depth insights
      into structure-property relationships for guiding development of high-mobility
      OFET polymers.

PMID- 28451361
TI  - Vapor-solid synthesis of monolithic single-crystalline CoP nanowire electrodes
      for efficient and robust water electrolysis.
AB  - Electrochemical water splitting into hydrogen and oxygen is a promising
      technology for sustainable energy storage. The development of earth-abundant
      transition metal phosphides (TMPs) to catalyze the hydrogen evolution reaction
      (HER) and TMP-derived oxy-hydroxides to catalyze the oxygen evolution reaction
      (OER) has recently drawn considerable attention. However, most monolithically
      integrated metal phosphide electrodes are prepared by laborious multi-step
      methods and their operational stability at high current densities has been rarely
      studied. Herein, we report a novel vapor-solid synthesis of single-crystalline
      cobalt phosphide nanowires (CoP NWs) on a porous Co foam and demonstrate their
      use in overall water splitting. The CoP NWs grown on the entire surface of the
      porous Co foam ligaments have a large aspect ratio, and hence are able to provide
      a large catalytically accessible surface over a given geometrical area.
      Comprehensive investigation shows that under the OER conditions CoP NWs are
      progressively and conformally converted to CoOOH through electrochemical in situ
      oxidation/dephosphorization; the latter serving as an active species to catalyze
      the OER. The in situ oxidized electrode shows exceptional electrocatalytic
      performance for the OER in 1.0 M KOH, delivering 100 mA cm-2 at an overpotential
      (eta) of merely 300 mV and a small Tafel slope of 78 mV dec-1 as well as
      excellent stability at various current densities. Meanwhile, the CoP NW electrode
      exhibits superior catalytic activity for the HER in the same electrolyte,
      affording -100 mA cm-2 at eta = 244 mV and showing outstanding stability. An
      alkaline electrolyzer composed of two symmetrical CoP NW electrodes can deliver
      10 and 100 mA cm-2 at low cell voltages of 1.56 and 1.78 V, respectively. The CoP
      NW electrolyzer demonstrates exceptional long-term stability for overall water
      splitting, capable of working at 20 and 100 mA cm-2 for 1000 h without obvious
      degradation.

PMID- 28451362
TI  - Redox-active triazatruxene-based conjugated microporous polymers for high
      performance supercapacitors.
AB  - Conjugated polymers (CPs) have been intensively explored for various
      optoelectronic applications in the last few decades. Nevertheless, CP based
      electrochemical energy storage devices such as supercapacitors remain largely
      unexplored. This is mainly owing to the low specific capacitance, poor
      structural/electrochemical stability, and low energy density of most existing
      CPs. In this contribution, a novel set of redox-active conjugated microporous
      polymers, TAT-CMP-1 and TAT-CMP-2, based on nitrogen-rich and highly conductive
      triazatruxene building blocks, were successfully designed and synthesized to
      explore their potential application as efficient and stable electrode materials
      for supercapacitors. Despite a moderate surface area of 88 m2 g-1 for TAT-CMP-1
      and 106 m2 g-1 for TAT-CMP-2, exceptional specific capacitances of 141 F g-1 and
      183 F g-1 were achieved at a current density of 1 A g-1. The resulting polymers
      exhibited unusually high areal specific capacitance (>160 MUF cm-2), which is
      attributed to the pseudocapacitance resulting from redox-active structures with
      high nitrogen content. More importantly, the TAT-CMP-2 electrode exhibits
      excellent cycling stability: only 5% capacitance fading is observed after 10 000
      cycles at a high current density of 10 A g-1, enabling the possible use of these
      materials as electrodes in electrochemical devices.

PMID- 28451363
TI  - A specific fluorescent probe reveals compromised activity of methionine sulfoxide
      reductases in Parkinson's disease.
AB  - Oxidation of methionine residues to methionine sulfoxide (MetSO) may cause
      changes in protein structure and function, and may eventually lead to cell
      damage. Methionine sulfoxide reductases (Msrs) are the only known enzymes that
      catalyze the reduction of MetSO back to methionine by taking reducing equivalents
      from the thioredoxin system, and thus protect cells from oxidative damage.
      Nonetheless, a lack of convenient assays for the enzymes hampers the exploration
      of their functions. We report the discovery of Msr-blue, the first turn-on
      fluorescent probe for Msr with a >100-fold fluorescence increment from screening
      a rationally-designed small library. Intensive studies demonstrated the specific
      reduction of Msr-blue by the enzymes. Msr-blue is ready to determine Msr activity
      in biological samples and live cells. Importantly, we disclosed a decline of Msr
      activity in a Parkinson's model, thus providing a mechanistic linkage between the
      loss of function of Msrs and the development of neurodegeneration. The strategy
      for the discovery of Msr-blue would also provide guidance for developing novel
      probes with longer excitation/emission wavelengths and specific probes for Msr
      isoforms.

PMID- 28451364
TI  - Sequential water molecule binding enthalpies for aqueous nanodrops containing a
      mono-, di- or trivalent ion and between 20 and 500 water molecules.
AB  - Sequential water molecule binding enthalpies, DeltaHn,n-1, are important for a
      detailed understanding of competitive interactions between ions, water and solute
      molecules, and how these interactions affect physical properties of ion
      containing nanodrops that are important in aerosol chemistry. Water molecule
      binding enthalpies have been measured for small clusters of many different ions,
      but these values for ion-containing nanodrops containing more than 20 water
      molecules are scarce. Here, DeltaHn,n-1 values are deduced from high-precision
      ultraviolet photodissociation (UVPD) measurements as a function of ion identity,
      charge state and cluster size between 20-500 water molecules and for ions with
      +1, +2 and +3 charges. The DeltaHn,n-1 values are obtained from the number of
      water molecules lost upon photoexcitation at a known wavelength, and modeling of
      the release of energy into the translational, rotational and vibrational motions
      of the products. The DeltaHn,n-1 values range from 36.82 to 50.21 kJ mol-1. For
      clusters containing more than ~250 water molecules, the binding enthalpies are
      between the bulk heat of vaporization (44.8 kJ mol-1) and the sublimation
      enthalpy of bulk ice (51.0 kJ mol-1). These values depend on ion charge state for
      clusters with fewer than 150 water molecules, but there is a negligible
      dependence at larger size. There is a minimum in the DeltaHn,n-1 values that
      depends on the cluster size and ion charge state, which can be attributed to the
      competing effects of ion solvation and surface energy. The experimental DeltaHn,n
      1 values can be fit to the Thomson liquid drop model (TLDM) using bulk ice
      parameters. By optimizing the surface tension and temperature change of the
      logarithmic partial pressure for the TLDM, the experimental sequential water
      molecule binding enthalpies can be fit with an accuracy of +/-3.3 kJ mol-1 over
      the entire range of cluster sizes.

PMID- 28451365
TI  - Expanding a fluorescent RNA alphabet: synthesis, photophysics and utility of
      isothiazole-derived purine nucleoside surrogates.
AB  - A series of emissive ribonucleoside purine mimics, all comprised of an
      isothiazolo[4,3-d]pyrimidine core, was prepared using a divergent pathway
      involving a key Thorpe-Ziegler cyclization. In addition to an adenosine and a
      guanosine mimic, analogues of the noncanonical xanthosine, isoguanosine, and 2
      aminoadenosine were also synthesized and found to be emissive. Isothiazolo 2
      aminoadenosine, an adenosine surrogate, was found to be particularly emissive and
      effectively deaminated by adenosine deaminase. Competitive studies with adenosine
      deaminase with each analogue in combination with native adenosine showed
      preference for the native substrate while still deaminating the isothiazolo
      analogues.

PMID- 28451366
TI  - An efficient on-board metal-free nanocatalyst for controlled room temperature
      hydrogen production.
AB  - Positively charged functionalized carbon nanodots (CNDs) with a variety of
      different effective surface areas (ESAs) are synthesized via a cheap and time
      effective microwave method and applied for the generation of hydrogen via
      hydrolysis of sodium borohydride. To the best of our knowledge, this is the first
      report of metal-free controlled hydrogen generation. Our observation is that a
      positively charged functional group is essential for the hydrolysis for hydrogen
      production, but the overall activity is found to be enhanced with the ESA. A
      maximum value of 1066 ml g-1 min-1 as the turnover frequency is obtained which is
      moderate in comparison to other catalysts. However, the optimum activation energy
      is found to be 22.01 kJ mol-1 which is comparable to well-known high cost
      materials like Pt and Ru. All of the samples showed good reusability and 100%
      conversion even after the 10th cycle. The effect of H+ and OH- is also studied to
      control the on-board and on-demand hydrogen production ("on-off switching"). It
      is observed that H2 production decreases inversely with NaOH concentration and
      ceases completely when 10-1 M NaOH is added. With the addition of HCl, H2
      production can be initiated again, which confirms the on/off control over
      production.

PMID- 28451367
TI  - Rhodium(i)-catalyzed stereoselective [4+2] cycloaddition of oxetanols with
      alkynes through C(sp3)-C(sp3) bond cleavage.
AB  - An efficient and convenient synthesis of highly functionalized dihydropyrans has
      been achieved through rhodium(i)-catalysed tandem C(sp3)-C(sp3) bond cleavage and
      annulation of oxetanols with alkynes. An enantioselective version was enabled
      using a Binaphine ligand. Excellent site-selectivity and remarkable
      enantioretention are obtained for 2-substituted oxetanols.

PMID- 28451368
TI  - A tendril perversion in a helical oligomer: trapping and characterizing a mobile
      screw-sense reversal.
AB  - Helical oligomers of achiral monomers adopt domains of uniform screw sense, which
      are occasionally interrupted by screw-sense reversals. These rare, elusive, and
      fast-moving features have eluded detailed characterization. We now describe the
      structure and habits of a screw-sense reversal trapped within a fragment of a
      helical oligoamide foldamer of the achiral quaternary amino acid 2
      aminoisobutyric acid (Aib). The reversal was enforced by compelling the amide
      oligomer to adopt a right-handed screw sense at one end and a left-handed screw
      sense at the other. The trapped reversal was characterized by X-ray
      crystallography, and its dynamic properties were monitored by NMR and circular
      dichroism, and modelled computationally. Raman spectroscopy indicated that a
      predominantly helical architecture was maintained despite the reversal. NMR and
      computational results indicated a stepwise shift from one screw sense to another
      on moving along the helical chain, indicating that in solution the reversal is
      not localised at a specific location, but is free to migrate across a number of
      residues. Analogous unconstrained screw-sense reversals that are free to move
      within a helical structure are likely to provide the mechanism by which
      comparable helical polymers and foldamers undergo screw-sense inversion.

PMID- 28451369
TI  - Supramolecular anion recognition in water: synthesis of hydrogen-bonded
      supramolecular frameworks.
AB  - The interaction of tetratopic amidinium-containing receptors with terephthalate
      anions leads to porous framework materials assembled through charge-assisted
      hydrogen bonds. The frameworks form in good yield within minutes in water at room
      temperature, but no framework material is obtained if other anions (Cl-, Br-, NO3
      , SO42- or isophthalate2-) are used in place of terephthalate. Two forms of the
      framework can be prepared: one with a connected pore network, and a more dense
      phase with discrete voids. We demonstrate that these are the kinetic and
      thermodynamic products, respectively. Either framework can be prepared
      independently and can be converted to the other form in response to stimuli.
      Furthermore, the frameworks can be controllably disassembled and reassembled in
      response to acid/base triggers suggesting that this new class of materials may
      have applications in the selective encapsulation and release of guests.

PMID- 28451370
TI  - Organocatalytic, enantioselective synthesis of benzoxaboroles via Wittig/oxa
      Michael reaction Cascade of alpha-formyl boronic acids.
AB  - An unprecedented enantioselective synthesis of 3-substituted benzoxaboroles has
      been developed. An in situ generated ortho-boronic acid containing chalcone
      provides the chiral benzoxaboroles via an asymmetric oxa-Michael addition of
      hydroxyl group attached to the boronic acid triggered by the cinchona alkaloid
      based chiral amino-squaramide catalysts. In general, good yields with good to
      excellent enantioselectivities (up to 99%) were obtained. The resulting
      benzoxaboroles were converted to the corresponding chiral beta-hydroxy ketones
      without affecting the enantioselectivity.

PMID- 28451371
TI  - Acid/base triggered interconversion of MU-eta2:eta2-peroxido and bis(MU-oxido)
      dicopper intermediates capped by proton-responsive ligands.
AB  - CuII2(MU-eta2:eta2-peroxido) and CuIII2(MU-oxido)2 cores represent key
      intermediates in copper/dioxygen chemistry, and they are mechanistically
      important for biological hydroxylation and oxidation reactions mediated by
      dinuclear (type III) copper metalloenzymes. While the exact nature of the active
      species in different enzymes is still under debate, shifting equilibria between
      Cu x /O2 species is increasingly recognized as a means of switching between
      distinct reactivity patterns of these intermediates. Herein we report
      comprehensive spectroscopic, crystallographic and computational analysis of a
      family of synthetic CuII2(MU-eta2:eta2-peroxido) and CuIII2(MU-oxido)2 dicopper
      complexes with a bis(oxazoline) (BOX) capping ligand. In particular, we
      demonstrate that a reversible peroxido/bis(MU-oxido) interconversion of the
      [Cu2O2] core can be triggered by peripheral (de)protonation events on the ligand
      backbone. As the copper ions in the enzymes are typically supported by histidine
      imidazoles that offer a backside N atom amenable to potential (de)protonation, it
      is well conceivable that the shifting of equilibria between the [Cu2O2] species
      in response to changes in local pH is biologically relevant.

PMID- 28451372
TI  - Plasmonic labeling of subcellular compartments in cancer cells: multiplexing with
      fine-tuned gold and silver nanoshells.
AB  - Fine-tuned gold and silver nanoshells were produced via an entirely reformulated
      synthesis. The new method yielded ultramonodisperse samples, with polydispersity
      indexes (PI) as low as 0.02 and narrow extinction bands suited for multiplex
      analysis. A library of nanoshell samples with localized surface plasmon
      resonances (LSPR) spanning across the visible range was synthesized.
      Hyperspectral analysis revealed that the average scattering spectrum of 100
      nanoshells matched closely to the spectrum of a single nanoshell, indicating an
      unprecedented low level of nanoparticle-to-nanoparticle variation for this type
      of system. A cell labeling experiment, targeting different subcellular
      compartments in MCF-7 human breast cancer cells, demonstrated that these
      monodisperse nanoparticles can be used as a multiplex platform for single cell
      analysis at the intracellular and extracellular level. Antibody-coated gold
      nanoshells targeted the plasma membrane, while silver nanoshells coated with a
      nuclear localization signal (NLS) targeted the nuclear membrane. A fluorescence
      counterstaining experiment, as well as single cell hyperspectral microscopy
      showed the excellent selectivity and specificity of each type of nanoparticle for
      its designed subcellular compartment. A time-lapse photodegradation experiment
      confirmed the enhanced stability of the nanoshells over fluorescent labeling and
      their capabilities for long-term live cell imaging.

PMID- 28451373
TI  - Enzyme-triggered compound release using functionalized antimicrobial peptide
      derivatives.
AB  - Controlled release is one of the key technologies for medical innovation, and
      many stimulus-responsive nanocarriers have been developed to utilize this
      technology. Enzyme activity is one of the most useful stimuli, because many
      enzymes are specifically activated in diseased tissues. However, controlled
      release stimulated by enzyme activity has not been frequently reported. One of
      the reasons for this is the lack of versatility of carriers. Most of the reported
      stimulus-responsive systems involve a sophisticated design and a complicated
      process for the synthesis of stimulus-responsive nanocarrier components. The
      purpose of this study was to develop versatile controlled release systems
      triggered by various stimuli, including enzyme activity, without modifying the
      nanocarrier components. We developed two controlled release systems, both of
      which comprised a liposome as the nanocarrier and a membrane-damaging peptide,
      temporin L (TL), and its derivatives as the release-controllers. One system
      utilized branched peptides for proteases, and the other utilized phosphopeptides
      for phosphatases. In our systems, the target enzymes converted the non-membrane
      damaging TL derivatives into membrane-damaging peptides and released the liposome
      inclusion. We demonstrated the use of our antimicrobial peptide-based controlled
      release systems for different enzymes and showed the promise of this technology
      as a novel theranostic tool.

PMID- 28451374
TI  - Resonances of the anthracenyl anion probed by frequency-resolved photoelectron
      imaging of collision-induced dissociated anthracene carboxylic acid.
AB  - Resonances in polyaromatic hydrocarbon (PAH) anions are key intermediates in a
      number of processes such as electron transfer in organic electronics and electron
      attachment in the interstellar medium. Here we present a frequency- and angle
      resolved photoelectron imaging study of the 9-anthracenyl anion generated through
      collision induced dissociation (CID) of its electrosprayed deprotonated
      anthracene carboxylic acid anion. We show that a number of pi* resonances are
      active in the first 2.5 eV above the threshold. The photoelectron spectra and
      angular distributions revealed that nuclear dynamics compete with autodetachment
      for one of the resonances, while higher-lying resonances were dominated by prompt
      autodetachment. Based on electronic structure calculations, these observations
      were accounted for on the basis of the expected autodetachment rates of the
      resonances. Virtually no ground state recovery was observed, suggesting that the
      smallest deprotonated PAH that leads to ground state recovery is the tetracenyl
      anion, for which clear thermionic emission has been observed. The use of CID and
      photodissociation of organic carboxylic acid anions is discussed as a route to
      studying the dynamics of resonances in larger PAH anions.

PMID- 28451375
TI  - Unravelling the mechanisms of vibrational relaxation in solution.
AB  - We present a systematic study of the mode-specific vibrational relaxation of NO2
      in six weakly-interacting solvents (perfluorohexane, perfluoromethylcyclohexane,
      perfluorodecalin, carbon tetrachloride, chloroform, and d-chloroform), chosen to
      elucidate the dominant energy transfer mechanisms in the solution phase.
      Broadband transient vibrational absorption spectroscopy has allowed us to extract
      quantum state-resolved relaxation dynamics of the two distinct NO2 fragments
      produced from the 340 nm photolysis of N2O4 -> NO2(X) + NO2(A) and their separate
      paths to thermal equilibrium. Distinct relaxation pathways are observed for the
      NO2 bending and stretching modes, even at energies as high as 7000 cm-1 above the
      potential minimum. Vibrational energy transfer is governed by different
      interaction mechanisms in the various solvent environments, and proceeds with
      timescales ranging from 20-1100 ps. NO2 relaxation rates in the perfluorocarbon
      solvents are identical despite differences in acceptor mode state densities,
      infrared absorption cross sections, and local solvent structure. Vibrational
      energy is shown to be transferred to non-vibrational solvent degrees of freedom
      (V-T) through impulsive collisions with the perfluorocarbon molecules.
      Conversely, NO2 relaxation in chlorinated solvents is reliant on vibrational
      resonances (V-V) while V-T energy transfer is inefficient and thermal excitation
      of the surrounding solvent molecules inhibits faster vibrational relaxation
      through direct complexation. Intramolecular vibrational redistribution allows the
      symmetric stretch of NO2 to act as a gateway for antisymmetric stretch energy to
      exit the molecule. This study establishes an unprecedented level of detail for
      the cooling dynamics of a solvated small molecule, and provides a benchmark
      system for future theoretical studies of vibrational relaxation processes in
      solution.

PMID- 28451376
TI  - Solar H2 evolution in water with modified diketopyrrolopyrrole dyes immobilised
      on molecular Co and Ni catalyst-TiO2 hybrids.
AB  - A series of diketopyrrolopyrrole (DPP) dyes with a terminal phosphonic acid group
      for attachment to metal oxide surfaces were synthesised and the effect of side
      chain modification on their properties investigated. The organic photosensitisers
      feature strong visible light absorption (lambda = 400 to 575 nm) and
      electrochemical and fluorescence studies revealed that the excited state of all
      dyes provides sufficient driving force for electron injection into the TiO2
      conduction band. The performance of the DPP chromophores attached to TiO2
      nanoparticles for photocatalytic H2 evolution with co-immobilised molecular Co
      and Ni catalysts was subsequently studied, resulting in solar fuel generation
      with a dye-sensitised semiconductor nanoparticle system suspended in water
      without precious metal components. The performance of the DPP dyes in
      photocatalysis did not only depend on electronic parameters, but also on
      properties of the side chain such as polarity, steric hinderance and
      hydrophobicity as well as the specific experimental conditions and the nature of
      the sacrificial electron donor. In an aqueous pH 4.5 ascorbic acid solution with
      a phosphonated DuBois-type Ni catalyst, a DPP-based turnover number (TONDPP) of
      up to 205 was obtained during UV-free simulated solar light irradiation (100 mW
      cm-2, AM 1.5G, lambda > 420 nm) after 1 day. DPP-sensitised TiO2 nanoparticles
      were also successfully used in combination with a hydrogenase or platinum instead
      of the synthetic H2 evolution catalysts and the platinum-based system achieved a
      TONDPP of up to 2660, which significantly outperforms an analogous system using a
      phosphonated Ru tris(bipyridine) dye (TONRu = 431). Finally, transient absorption
      spectroscopy was performed to study interfacial recombination and dye
      regeneration kinetics revealing that the different performances of the DPP dyes
      are most likely dictated by the different regeneration efficiencies of the
      oxidised chromophores.

PMID- 28451377
TI  - DNA-barcoded labeling probes for highly multiplexed Exchange-PAINT imaging.
AB  - Recent advances in super-resolution fluorescence imaging allow researchers to
      overcome the classical diffraction limit of light, and are already starting to
      make an impact in biology. However, a key challenge for traditional super
      resolution methods is their limited multiplexing capability, which prevents a
      systematic understanding of multi-protein interactions on the nanoscale. Exchange
      PAINT, a recently developed DNA-based multiplexing approach, in theory
      facilitates spectrally-unlimited multiplexing by sequentially imaging target
      molecules using orthogonal dye-labeled 'imager' strands. While this approach
      holds great promise for the bioimaging community, its widespread application has
      been hampered by the availability of DNA-conjugated ligands for protein labeling.
      Herein, we report a universal approach for the creation of DNA-barcoded labeling
      probes for highly multiplexed Exchange-PAINT imaging, using a variety of affinity
      reagents such as primary and secondary antibodies, nanobodies, and small molecule
      binders. Furthermore, we extend the availability of orthogonal imager strands for
      Exchange-PAINT to over 50 and assay their orthogonality in a novel DNA origami
      based crosstalk assay. Using our optimized conjugation and labeling strategies,
      we demonstrate nine-color super-resolution imaging in situ in fixed cells.

PMID- 28451379
TI  - Retrospective analysis in oculocutaneous albinism patients for the 2.7 kb
      deletion in the OCA2 gene revealed a co-segregation of the controversial variant,
      p.R305W.
AB  - BACKGROUND: Oculocutaneous albinism (OCA) is an autosomal recessive disorder. A
      significant portion of OCA patients has been found with a single pathogenic
      variant either in the TYR or the OCA2 gene. Diagnostic sequencing of the TYR and
      OCA2 genes is routinely used for molecular diagnosis of OCA subtypes. To study
      the possibility that genomic abnormalities with single or multiple exon
      involvement may account for a portion of the potential missing pathogenic
      variants (the second), we retrospectively analyzed the TYR gene by long range PCR
      and analyzed the target 2.7 kb deletion in the OCA2 gene spanning exon 7 in OCA
      patients with a single pathogenic variant in the target genes. RESULTS: In the
      108 patients analyzed, we found that one patient was heterozygous for the 2.7 kb
      OCA2 gene deletion and this patient was positive with one pathogenic variant and
      one possibly pathogenic variant [c.1103C>T (p.Ala368Val) + c.913C>T (p.R305W)].
      Further analysis of maternal DNA, and two additional OCA DNA homozygous for the
      2.7 kb deletion, revealed that the phenotypically normal mother is heterozygous
      of the 2.7 kb deletion and homozygous of the p.R305W. The two previously reported
      patients with homozygous of the 2.7 kb deletion are also homozygous of p.R305W.
      CONCLUSIONS: Among the reported pathogenic variants, the pathogenicity of the
      p.R305W has been discussed intensively in literature. Our results indicate that
      p.R305W is unlikely a pathogenic variant. The possibility of linkage
      disequilibrium between p.R305W with the 2.7 kb deletion in OCA2 gene is also
      suggested.

PMID- 28451381
TI  - MetaGenSense : A web application for analysis and visualization of high
      throughput sequencing metagenomic data.
AB  - The detection and characterization of emerging infectious agents has been a
      continuing public health concern. High Throughput Sequencing (HTS) or Next
      Generation Sequencing (NGS) technologies have proven to be promising approaches
      for efficient and unbiased detection of pathogens in complex biological samples,
      providing access to comprehensive analyses. As NGS approaches typically yield
      millions of putatively representative reads per sample, efficient data management
      and visualization resources have become mandatory. Most usually, those resources
      are implemented through a dedicated Laboratory Information Management System
      (LIMS), solely to provide perspective regarding the available information. We
      developed an easily deployable web-interface, facilitating management and
      bioinformatics analysis of metagenomics data-samples. It was engineered to run
      associated and dedicated Galaxy workflows for the detection and eventually
      classification of pathogens. The web application allows easy interaction with
      existing Galaxy metagenomic workflows, facilitates the organization, exploration
      and aggregation of the most relevant sample-specific sequences among millions of
      genomic sequences, allowing them to determine their relative abundance, and
      associate them to the most closely related organism or pathogen. The user
      friendly Django-Based interface, associates the users' input data and its
      metadata through a bio-IT provided set of resources (a Galaxy instance, and both
      sufficient storage and grid computing power). Galaxy is used to handle and
      analyze the user's input data from loading, indexing, mapping, assembly and DB
      searches. Interaction between our application and Galaxy is ensured by the
      BioBlend library, which gives API-based access to Galaxy's main features.
      Metadata about samples, runs, as well as the workflow results are stored in the
      LIMS. For metagenomic classification and exploration purposes, we show, as a
      proof of concept, that integration of intuitive exploratory tools, like Krona for
      representation of taxonomic classification, can be achieved very easily. In the
      trend of Galaxy, the interface enables the sharing of scientific results to
      fellow team members.

PMID- 28451380
TI  - Which factors affect the implementation of geriatric recommendations by primary
      care physicians?
AB  - BACKGROUND: The overall implementation rate for outpatient comprehensive
      geriatric assessment (OCGAU) recommendations ranges from 48.6 to 71%. The purpose
      of the study was to identify factors that reduce the implementation rate of
      geriatric recommendations. METHODS: The medical records of patients who were
      assessed in the comprehensive geriatric assessment unit over an 8 year study
      period were surveyed. Data collected included patient's characteristics (socio
      demographic, functional, cognitive, and affective condition, co-morbidity),
      number of recommendations, the identity of the geriatrician, and data related to
      the primary physician (age, sex, seniority, number of patients referred for
      geriatric assessment). RESULTS: Three thousand four hundred thirty-four
      recommendations were made for 488 patients (mean age 83.6 +/- 0.6 years) of which
      1,634 (47.6%) were implemented by their primary physician. In univariate analyses
      patients with an implementation rate < 25%, compared to patients with
      implementation rate >=75%, had a higher Charlson Comorbidity Index Total Score
      (CCITS) (2.5 +/- 1.9 vs. 1.8 +/- 1.7, P < 0.05), a lower Barthel Index (82.8 +/-
      16.2 vs. 87.0 +/- 15.3, P < 0.05), and a lower Instrumental Activity of Daily
      Living score (7.2 +/- 3.5 vs. 8.2 +/- 3.7, P < 0.05). There were no differences
      between these groups in other patient characteristics or the number of
      recommendations made during the assessment. Similarly, there were no differences
      in the identity of the geriatrician or the primary physician's characteristics.
      In the multivariate analysis only higher CCITS was associated with a lower rate
      of recommendation implementation by primary physicians. CONCLUSIONS: There is a
      need to increase the implementation rate by primary physicians by increasing and
      strengthening the link with them and by further training in the field of
      geriatrics medicine. TRIAL REGISTRATION: The Helsinki committee of the Meir
      Medical Center approved the study (Approval #024/2015 [k]).

PMID- 28451378
TI  - Plant genome editing with TALEN and CRISPR.
AB  - Genome editing promises giant leaps forward in advancing biotechnology,
      agriculture, and basic research. The process relies on the use of sequence
      specific nucleases (SSNs) to make DNA double stranded breaks at user defined
      genomic loci, which are subsequently repaired by two main DNA repair pathways:
      non-homologous end joining (NHEJ) and homology directed repair (HDR). NHEJ can
      result in frameshift mutations that often create genetic knockouts. These
      knockout lines are useful for functional and reverse genetic studies but also
      have applications in agriculture. HDR has a variety of applications as it can be
      used for gene replacement, gene stacking, and for creating various fusion
      proteins. In recent years, transcription activator-like effector nucleases and
      clustered regularly interspaced palindromic repeats (CRISPR) and CRISPR
      associated protein 9 or CRISPR from Prevotella and Francisella 1 have emerged as
      the preferred SSNs for research purposes. Here, we review their applications in
      plant research, discuss current limitations, and predict future research
      directions in plant genome editing.

PMID- 28451382
TI  - Roles of functional catechol-O-methyltransferase genotypes in Chinese patients
      with Parkinson's disease.
AB  - BACKGROUND: Recent studies have found that the functional catechol-O
      methyltransferase (COMT) gene may be associated with the susceptibility to and
      pharmacotherapy of Parkinson's disease (PD). In this case-control study, we
      investigated the most common functional COMT gene haplotypes that had been shown
      to influence COMT enzymatic activity and the association of the single and
      combined COMT haplotypes with clinical symptoms and pharmacotherapy in Chinese
      patients with PD. METHODS: One hundred forty-three patients with idiopathic PD
      and 157 healthy individuals were enrolled in this study. Four single nucleotide
      polymorphisms (SNPs) in the COMT gene (formed by SNPs) were genotyped in each
      participant: rs6269 A > G; rs4633 C > T; rs4818 C > G; and rs4680 G > A. RESULTS:
      The frequencies of rs4633 T carriers, rs4680 A carriers and the two linked rs4633
      rs4680 T/A carriers were significantly higher in the early onset PD group than in
      the healthy controls (all P < 0.05). Homozygosity for rs4633 (TT), rs4680 (AA)
      and of the two linked rs4633-rs4680 (TT/AA) was significantly more frequent in
      patients who exhibited the "wearing-off" phenomenon, longer disease duration,
      higher levodopa equivalent doses (LED) and higher Unified Parkinson's Disease
      Rating Scale (UPDRS) scores (P < 0.05). No significant differences were observed
      in the clinical features of patients who carried individual rs6269 and rs4818,
      the two linked rs6269-rs4818 and the four combined COMT SNPs. CONCLUSIONS: The
      results showed a possible association of combined functional COMT SNPs with PD
      risk, disease duration, the "wearing-off" phenomenon, daily LEDs and higher UPDRS
      scores, which may be useful in instituting individualized therapy for patients
      with PD.

PMID- 28451384
TI  - Chemotherapy-induced peripheral neuropathy.
AB  - Neuropathy is associated with side effects of frontline chemotherapeutics, which
      is a prominent therapy utilized in prevalent cancers. Peripheral neuropathy
      negatively impacts quality of life in cancer patients and survivors. It also
      affects the dose plan of the treatment, thereby limiting the efficacy of the
      treatment. We searched the electronic database PubMed for pre-clinically and
      clinically controlled trials reporting neuropathy of adverse effects, a result of
      chemotherapy in cancer patients. It was observed clearly that many reports
      provide clinical evidence to rapidly growing neuropathy cases of cancer patients.
      Furthermore, the reports clearly showed enhanced cold pain, sensorimotor
      deficits, sensory innervation of the skin and sensorimotor deficits in the
      patients with cancer who underwent treatment mainly with the chemotherapeutic
      approach. The present review highlighted the current view of peripheral
      neuropathy during chemotherapeutic approaches.

PMID- 28451383
TI  - Animal models of atherosclerosis.
AB  - Atherosclerosis is a significant cause of morbidity and mortality globally. Many
      animal models have been developed to study atherosclerosis, and permit
      experimental conditions, diet and environmental risk factors to be carefully
      controlled. Pathophysiological changes can be produced using genetic or
      pharmacological means to study the harmful consequences of different
      interventions. Experiments using such models have elucidated its molecular and
      pathophysiological mechanisms, and provided platforms for pharmacological
      development. Different models have their own advantages and disadvantages, and
      can be used to answer different research questions. In the present review
      article, different species of atherosclerosis models are outlined, with
      discussions on the practicality of their use for experimentation.

PMID- 28451385
TI  - A network pharmacology approach to establish the pharmacological mechanism of
      JiaWeiXianJiTang on inflammatory bowel disease.
AB  - The aim of the present study was to characterize the molecular mechanism of the
      effective components of JiaWeiXianJiTang (JWXJT), a traditional Chinese medicine,
      on inflammatory bowel disease (IBD) using network pharmacology technology. Data
      regarding natural molecules of JWXJT, targets of IBD, and interactions between
      natural molecules and IBD targets were screened. Network pharmacology of the
      interactions between natural molecules and IBD targets were drawn using Cytoscape
      v3.2.1. As a result of screening, 205 interactions were identified between 673
      natural molecules and 76 targets of IBD. By analyzing the effective components,
      the complex effect mechanism of JWXJT on IBD was identified to be via enhancement
      of the immune system, inhibiting novel blood vessel growth through 15
      hydroxyprostaglandin dehydrogenase, 5' AMP-activated protein kinase, interleukin
      2 and macrophage colony-stimulating factor-1, and resulting in inflammation
      inhibition. In addition, JWXJT ameliorated IBD by antagonizing various molecular
      targets of IBD through its effective components, inhibiting inflammatory
      reactions, improving patient quality of life, as well as reducing the incidence
      of cancer.

PMID- 28451386
TI  - Potential of bone marrow mesenchymal stem cells in rejuvenation of the aged skin
      of rats.
AB  - The aim of the present study was to evaluate the anti-aging effects of bone
      marrow-mesenchymal stem cells (BM-MSCs) in a D-galactose-induced skin aging rat
      model. Male Sprague Dawley rats were randomly divided into four groups
      (n=10/group) as follows: Normal control group; skin aging model group; MSC
      treated group by subcutaneous multi-point injection. The skin aging model was
      established by a daily subcutaneous injection of 15% D-galactose (1,000 mg/kg)
      for 8 weeks. Rats in the MSC-treated groups were administered 3*106/ml BM
      MSCs/green fluorescent protein (GFP) for 4 weeks, administered once per week.
      Oxidative/antioxidative parameters were evaluated, and morphological and
      ultrastructure analyses were performed. Rats in the model group exhibited the
      typical changes of aging skin. Compared with the control group, rats in the model
      group had significantly increased malondialdehyde (MDA) content (P<0.01), and
      decreased serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
      activities (P<0.05). MSC treatment markedly ameliorated aging-induced oxidative
      stress in the skin. Histologically, rats in the model group exhibited loosely
      arranged epidermal cell layers and disorganized collagen fibers. BM-MSC treatment
      significantly improved the histological abnormalities, which was similar to those
      in the control group. In addition, 7 days after the final cell transplantation,
      GFP-positive cells were observed by fluorescence microscopy to be distributed in
      the dermis. Injection of BM-MSCs significantly improved the D-galactose-induced
      histological abnormalities of the skin, by promoting an antioxidant response and
      ameliorating oxidative stress in aged skin. Thus, BM-MSCs may be beneficial in
      the rejuvenation of aged skin.

PMID- 28451387
TI  - Risperidone reverses the spatial object recognition impairment and hippocampal
      BDNF-TrkB signalling system alterations induced by acute MK-801 treatment.
AB  - The aim of the present study was to investigate the effects of a commonly-used
      atypical antipsychotic, risperidone, on alterations in spatial learning and in
      the hippocampal brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase
      B (TrkB) signalling system caused by acute dizocilpine maleate (MK-801)
      treatment. In experiment 1, adult male Sprague-Dawley rats subjected to acute
      treatment of either low-dose MK801 (0.1 mg/kg) or normal saline (vehicle) were
      tested for spatial object recognition and hippocampal expression levels of BDNF,
      TrkB and the phophorylation of TrkB (p-TrkB). We found that compared to the
      vehicle, MK-801 treatment impaired spatial object recognition of animals and
      downregulated the expression levels of p-TrkB. In experiment 2, MK-801- or
      vehicle-treated animals were further injected with risperidone (0.1 mg/kg) or
      vehicle before behavioural testing and sacrifice. Of note, we found that
      risperidone successfully reversed the deleterious effects of MK-801 on spatial
      object recognition and upregulated the hippocampal BDNF-TrkB signalling system.
      Collectively, the findings suggest that cognitive deficits from acute N-methyl-D
      aspartate receptor blockade may be associated with the hypofunction of
      hippocampal BDNF-TrkB signalling system and that risperidone was able to reverse
      these alterations.

PMID- 28451388
TI  - Myofilament function and body mass index.
AB  - Body mass is reported to influence myocardial performance. Recent studies have
      emphasised the importance of negative inotropic adipocyte-derived factors and
      their impact on cardiac contractile function. However, the underlying mechanisms
      remain unclear. We aimed to determine whether body mass impacts cardiac force
      development on the level of the contractile apparatus. We examined the influence
      of body mass index (BMI) (3 groups: group I >25, group II 25-30, group III >30)
      on the myocardial performance of skinned muscle fibres. Right atrial tissue
      preparations of 70 patients undergoing aortocoronary bypass operation (CABG, 48
      patients, group a) and aortic valve replacement (AVR, 22 patients, group b) were
      obtained. The fibres were exposed to a gradual increase in the calcium
      concentration, and the force values were recorded. The statistical analysis was
      performed using Pearson's correlation (P<0.05 significant). A BMI >30 (group III)
      was associated with less force (mean force 1.58+/-0.1 mN, P=0.02, max force
      2.24+/-0.17 mN, P=0.02 vs. group II (mean force 1.8+/-0.3 mN, P=0.04, max force
      2.59+/-0.2 mN, P=0.03) and group I (mean force 1.8+/-0.1 mN, P=0,03, max force
      2.62+/-0.3 mN, P=0.03). Dividing the groups in the post-surgical procedure, the
      impact of BMI on force development in group III was more intense in the CABG
      group compared to the AVR group: 2.0+/-0.2 mN vs. 2.4+/-0.1 mN, P=0.04. In
      accordance with the literature, a BMI >30 is associated with reduced force
      capacities. Additionally, the underlying cardiac disease may aggravate the impact
      of weight on cardiac force. Further studies are needed to evaluate the clinical
      relevance of this experimental observation and the potential consequences for the
      treatment of cardiac function.

PMID- 28451389
TI  - Effect of ephedrine combined with bupivacaine on maternal hemodynamic and spinal
      nerve block in cesarean delivery.
AB  - The aim of the study was to investigate the effects of ephedrine intrathecal
      injection on maternal thermodynamics and spinal nerve block in cesarean section.
      A total of 107 patients undergoing elective cesarean section under combined
      spinal epidural anesthesia were randomly divided into two groups: group E:
      Bupivacaine (6 mg) combined with ephedrine (15 mg) and group C: Bupivacaine (6
      mg). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate
      (HR), the incidence of hypotension, hypertension, tachycardia, nausea and
      vomiting were all recorded. The umbilical vein blood gases and noradrenaline, as
      well as maternal peripheral venous blood were analyzed. The time of high-quality
      spinal block was also recorded. Postoperatively, 1 day, 2 days bedside follow-up
      and 7, 21, 35 days telephone follow-up were carried out to determine any
      neurological deficit maternal performance. SBP and DBP decreased in group C but
      not in group E at 3 min after spinal anesthesia and 1 min after delivery
      (P<0.05). From 3 min post-anesthesia to the end of surgery, the HR levels in the
      C group were significantly higher than those of the E group (P<0.05). The
      incidence of hypotension, tachycardia, nausea and vomiting and neonate acidosis
      was low in group E compared with group C (P<0.05). The time of high-quality
      spinal block in group E was longer than that of group C (P<0.05). After spinal
      anesthesia, the concentration of noradrenaline from maternal peripheral venous
      blood was low in group C but high in group E compared with before spinal
      anesthesia (P<0.05). Ephedrine combined with low-dose bupivacaine intrathecal
      injection effectively maintained maternal hemodynamics and prolonged the time of
      sensory spinal block.

PMID- 28451390
TI  - Cell culture density affects the stemness gene expression of adipose tissue
      derived mesenchymal stem cells.
AB  - The results of clinical trials using mesenchymal stem cells (MSCs) are
      controversial due to the heterogeneity of human MSCs and differences in culture
      conditions. In this regard, it is important to identify gene expression patterns
      according to culture conditions, and to determine how the cells are expanded and
      when they should be clinically used. In the current study, stemness gene
      expression was investigated in adipose tissue-derived MSCs (AT-MSCs) harvested
      following culture at different densities. AT-MSCs were plated at a density of 200
      or 5,000 cells/cm2. After 7 days of culture, stemness gene expression was
      examined by reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) analysis. The proliferation rate of AT-MSCs harvested at a low density
      (~50% confluent) was higher than that of AT-MSCs harvested at a high density
      (~90% confluent). Although there were differences in the expression levels of
      stemness gene, such as octamer-binding transcription factor 4, nanog homeobox
      (Nanog), SRY-box 2, Kruppel like factor 4, v-myc avian myelocytomatosis viral
      oncogene homolog (c-Myc), and lin-28 homolog A, in the AT-MSCs obtained from
      different donors, RT-qPCR analysis demonstrated differential gene expression
      patterns according to the cell culture density. Expression levels of stemness
      genes, particularly Nanog and c-Myc, were upregulated in AT-MSCs harvested at a
      low density (~50% confluent) in comparison to AT-MSCs from the same donor
      harvested at a high density (~90% confluent). These results imply that culture
      conditions, such as the cell density at harvesting, modulate the stemness gene
      expression and proliferation of MSCs.

PMID- 28451391
TI  - Follow-up of multiple sclerosis patients treated with Endotherapia (GEMSP).
AB  - Endotherapia (GEMSP) is a novel therapeutic approach for multiple sclerosis (MS).
      The aim of the present study was to demonstrate the efficiency of Endotherapia in
      the follow-up of 193 patients with MS. The efficiency coefficient that was
      evaluated was the Expanded Disability Status Scale (EDSS) score, which is a
      functional scale of MS progression. The evaluated score of each patient during
      follow-up visits was compared with the theoretical score of the disease
      progression without GEMSP. The evolution of the EDSS score was evaluated
      according to the inclusion score. The quantitative global study of the EDSS score
      highlighted a statistically significant difference between the final average
      scores of the treatment with GEMSP (M) and worldwide reference (R) groups. The
      improvement of the M group compared with the R group was 24.5%. According to the
      final EDSS scores, the study highlighted a difference in favor of the M group
      with 62.0% for scores <=3, 7.8% for scores between 3 and 6 and 19.6% for scores
      >=6. According to the qualitative evolution of the EDSS scores, the improvements
      in favor of group M were 49.3% for scores <=3, 79.1% for scores between 3 and 6
      and 19.5% for scores >=6. The qualitative study of the EDSS score showed a
      statistically significant success percentage; the success percentages were
      between 59.1 and 90.0%. In a larger population of MS patients, the data confirm
      the beneficial effects of GEMSP that were previously reported in pre-clinical and
      clinical studies. In addition, 78% of patients showed an improvement or
      deceleration of the disease.

PMID- 28451392
TI  - Effect of trehalose on cryopreservation of pure peripheral blood stem cells.
AB  - Stem cells are an important tool for the study of hematopoiesis. Despite
      developments in cryopreservation, post-thaw cell death remains a considerable
      problem. Cryopreservation protocol should limit cell damage due to freezing and
      ensure the recovery of the functional cell characteristics after thawing. Thus,
      the use of cryoprotectants is essential. In particular, the efficacy of trehalose
      has been reported for clinical purposes in blood stem cells. The aim of the
      current study was to establish an efficient method for biological research based
      on the use of trehalose, to cryopreserve pure peripheral blood stem cells. The
      efficacy of trehalose was assessed in vitro and the cell viability was evaluated.
      The data indicate that trehalose improves cell survival after thawing compared
      with the standard freezing procedure. These findings could suggest the potential
      for future trehalose application for research purposes in cell cryopreservation.

PMID- 28451393
TI  - The circulating microRNA-200 family in whole blood are potential biomarkers for
      high-grade serous epithelial ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) is the leading cause of mortality with regard to
      gynaecological cancer. There is no effective biomarker and therefore prognosis is
      poor as the majority of cases are not diagnosed until advanced disease is
      present. MicroRNAs (miRs) are dysregulated in ovarian cancer tissue and are
      present in the circulation. The aim of the present study was to investigate
      whether circulating miRs from the miR-200 family served as potential candidate
      biomarkers for the early detection of EOC. Whole blood and ovarian tissue were
      collected from women with early (stage I/II, n=4), advanced EOC (stage III/IV,
      n=4), and women with benign ovarian masses (n=5). A panel of 5 miRs were studied
      in whole blood and ovarian tissue using Taqman RT-PCR miR assays. The expression
      of circulating miR-200a, miR-200b and miR-200c were upregulated (P<0.05) in
      ovarian cancer compared to controls, correlated with the stage of disease and
      reflected tissue expression. Despite a trend, there was no significant increase
      in the expression of miR-21 and miR-210 in the present study. In conclusion, the
      circulating miR-200 family may be promising candidate biomarkers for EOC that
      require validation in a larger study.

PMID- 28451394
TI  - ADAM33 gene polymorphisms identified to be associated with asthma in a Chinese Li
      population.
AB  - A disintegrin and metalloprotease 33 (ADAM33) is an asthma susceptibility gene
      that has been proven to be present in certain human populations. The Li
      population is a minority ethnic group, most of whom maintain a distinctive
      lifestyle on Hainan Island in southern China. To the best of our knowledge, no
      previous study has established whether ADAM33 polymorphisms are associated with
      asthma in the Li population. Therefore, the ADAM33 polymorphisms in a Li
      population were investigated in the present study. A total of 150 asthma patients
      and 100 healthy subjects were enrolled in the present study, and their DNA
      samples were evaluated to analyze eight single-nucleotide polymorphisms (SNPs) on
      the ADAM33 gene. Asthma patients were subcategorized into low and high severity
      groups, and their SNP data were compared with the data of the control subjects.
      Single-marker and haplotype association was analyzed to demonstrate the
      association between ADAM33 SNPs and asthma using multiple genetic statistic
      tests. The results indicated significant differences in allele frequencies at the
      SNPs rs44707/T2 (P=0.008), rs2787094/V4 (P=0.028) and rs2280089/T+1 (P=0.021)
      between asthma patients and control subjects. The SNP rs44707/T2 was also found
      to be associated with the high severity group (P=0.024), although SNPs
      rs2787094/V4 were associated with the low severity group (P=0.019). Two
      haplotypes, GGAGAGT and GAAGGGT, were significantly associated with asthma
      (P=0.003 and 0.008, respectively). To the best of our knowledge, this is the
      first time that SNP rs2280089/T+1 has been reported to be associated with asthma
      in an Asian population. These data confirm that ADAM33 polymorphisms are
      associated with asthma susceptibility in the Li population and confirm the
      uniqueness of the Li minority population within China.

PMID- 28451395
TI  - Association of COL4A3 (rs55703767), MMP-9 (rs17576)and TIMP-1 (rs6609533) gene
      polymorphisms with susceptibility to type 2 diabetes.
AB  - Type 2 diabetes (T2D) is defined by high levels of glucose in the blood. The
      collagen IV level is associated with conditions of hyperglycemia and insulin
      resistance. Collagen type IV alpha3 chain (COL4A3) is a structural protein of the
      extracellular matrix (ECM). Matrix metallopeptidase 9 (MMP-9) is an enzyme that
      degrades the extracellular matrix and its activity is moderated by TIMP
      metallopeptidase inhibitor 1 (TIMP-1). The aim of the current study was to
      examine the association between genetic polymorphisms of COL4A3 (rs55703767), MMP
      9 (rs17576) and TIMP-1 (rs6609533) in patients with T2D. This case-control study
      was performed on 120 Iranian patients with T2D and 120 healthy individuals.
      Genotypes were analyzed using the amplification refractory mutation system
      polymerase chain reaction technique. The findings demonstrated significant
      differences between genotypic and allelic distributions of COL4A3 (G/T) and MMP-9
      (A/G) polymorphisms as follows: COL4A3 (G/T); TT vs. GG, odds ratio (OR)=0.235,
      95% confidence interval (CI)=0.063-0.0802 (P=0.013) and T vs. G, OR=0.592, 95%
      CI=0.371-0.943 (P=0.026); MMP-9 (A/G); AG vs. GG, OR=2.429, 95% CI=1.232-4.820
      (P=0.008) and A vs. G, OR=2.176, 95% CI=1.155-4.130 (P=0.013). No significant
      association was identified between TIMP-1 (A/G) polymorphism and T2D in females
      and males. Thus, the genotypic and allelic distributions of COL4A3 (G/T) and MMP
      9 (A/G) polymorphisms were associated with T2D. In addition, no significant
      association was identified in the genotypic distribution of the TIMP-1 (A/G) gene
      in females and in males. Further studies in other ethnic groups are required to
      confirm these findings.

PMID- 28451396
TI  - Association between interleukin-1 receptor associated kinase 1 rs3027898 A/C gene
      polymorphism and rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease predominantly
      involving the synovial joints and affects up to 1% of adults worldwide. The aim
      of the present study was to determine whether the interleukin-1 receptor (IL1R)
      associated kinase (IRAK1) rs3027898 gene polymorphism confers susceptibility to
      RA in a sample of patients from Iran. This gene encodes IRAK1, one of two
      putative serine/threonine kinases that associates with IL1R upon stimulation.
      IRAK1 is partially responsible for IL-1-induced upregulation of the transcription
      factor, nuclear factor-kappaB. The present case-control study was performed on
      120 patients with RA and 120 healthy individuals. Genomic DNA was extracted from
      whole blood, and the gene polymorphism was evaluated using a tetra-primer
      amplification refractory mutation system-polymerase chain reaction method. The
      results demonstrated that there was no association between IRAK1 rs3027898 CA
      genotype and the risk of RA in women (odds ratio=0.72, 95% confidence
      interval=0.41-1.49; P=0.446). Further studies with larger sample sizes and
      different ethnicities are required to validate the present findings.

PMID- 28451397
TI  - Association of blood glucose and lipid levels with complete blood count indices
      to establish a regression model.
AB  - Hyperglycemia and hyperlipidemia, which are usually diagnosed by analysis of
      blood glucose (GLU) and lipid levels, are two of the most common diseases in
      modern society. The purpose of the current study was to investigate the potential
      association between blood GLU and lipid levels with complete blood count (CBC)
      indices in overweight and healthy individuals and establish a regression model.
      There were 456 healthy and 421 overweight participants in the study. Data were
      collected on triglyceride (TG), total cholesterol (CHO), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood GLU and
      CBC. The distribution characteristics and differences between healthy and
      overweight subjects were analyzed. Subsequently, the associations between TG,
      CHO, HDL, LDL and GLU with CBC were analyzed using correlation analysis and
      multiple linear regression (MLR). Significant differences were identified between
      the healthy and overweight individuals in TG, CHO, HDL, LDL, GLU and in the
      majority of the CBC indices. The correlation analysis indicated that there were
      strong correlations between TG, LDL, HDL, CHO and GLU with CBC indices in the
      healthy and overweight subjects. The MLR demonstrated that the regression models
      of TG, LDL, HDL and CHO, but no GLU, were statistically significant in the two
      groups (P<0.001). The HDL regression model exhibited the best regression
      parameters; the multiple correlation coefficients (R) were 0.351 and 0.308 in the
      healthy and overweight subjects, respectively. In the overweight and healthy
      subjects, there were strong correlations between TG, LDL, HDL and CHO with CBC
      indices, with HDL being the most relevant to the CBC indices. The CBC
      demonstrated statistical significance in the diagnosis of hyperlipidemia.

PMID- 28451398
TI  - Rosuvastatin reduces the recurrence rate following catheter ablation for atrial
      fibrillation in patients with heart failure.
AB  - The aim of the present study was to assess whether rosuvastatin could reduce the
      recurrence rate of atrial fibrillation (AF) in patients with heart failure (HF)
      following catheter ablation (CA). A total of 107 patients with HF and AF who
      underwent CA of AF by endocardial mapping and radiofrequency between June 2012
      and May 2014 were recruited. The patients were randomly divided into three
      subgroups: i) Administered with 10 mg rosuvastatin daily following ablation
      (group 1, n=36); ii) administered with 20 mg rosuvastatin daily following
      ablation (group 2, n=36); and iii) only treated with conventional treatment of HF
      following ablation (group 3, n=35). After the procedure, patients were followed
      in the outpatient clinic by interrogation of Holter monitoring. The AF recurrence
      rate of group 2 was low in comparison with group 1 (22.2% vs. 38.9%, P=0.013) and
      group 3 (22.2% vs. 48.6%, P=0.021). In comparison with baseline, the parameters
      of the left ventricular ejection fraction, left atrial diameter (LAD), and the
      levels of N-terminal pronatriuretic peptide and hypersensitive C-reactive protein
      (hs-CRP) were all improved in three groups. Furthermore, multivariate analysis
      demonstrated that LAD [hazard ratio (HR): 1.12, 95% confidence interval (CI):
      1.06-1.67, P=0.049], hs-CRP (HR: 1.37, 95% CI: 1.11-1.92, P=0.002) and duration
      of AF (HR: 1.14, 95% CI: 1.09-1.18, P=0.011) were independent predictors of AF
      recurrence in patients with HF following CA. Therefore, the present study has
      demonstrated that treatment with 20 mg rosuvastatin daily following CA was able
      to significantly decrease the recurrence rate of AF in patients with HF, and LAD,
      hs-CRP, and duration of AF were independent predictors of AF recurrence in
      patients with HF following CA. In conclusion, the present study has also
      demonstrated that CA may improve cardiac function in patients with HF and AF.

PMID- 28451399
TI  - Preliminary evaluation of circulating microRNAs as potential biomarkers in
      paracoccidioidomycosis.
AB  - MicroRNAs (miRNAs) are small RNAs (length, 19-24 nucleotides) that regulate gene
      expression by either mRNA degradation or translational inhibition of proteins.
      Circulating miRNAs, which are extremely stable and protected from RNAse-mediated
      degradation in body fluids, have appeared as candidate biomarkers for numerous
      diseases. However, little is known about circulating miRNAs in fungal infections.
      Paracoccidioidomycosis (PCM) is caused by the Paracoccidioides species, and is
      endemic in Central and South America, with predominance in adult male workers
      from rural areas. The current study aimed to identify a serum miRNA expression
      profile that could serve as a novel diagnostic biomarker for PCM. Total RNA was
      isolated and the levels of circulating miRNAs were compared between patients with
      PCM and healthy control subjects using reverse transcription-quantitative
      polymerase chain reaction. Bioinformatic analysis was used to evaluate the
      potential roles of these miRNAs in PCM. Eight miRNAs were differentially
      expressed in serum samples from patients with PCM. These miRNAs are associated
      with apoptosis and immune response. The identified miRNAs facilitate with
      understanding the regulatory mechanisms involved in the host-parasite interaction
      of PCM. Furthermore, considering that the diagnosis of PCM presents difficulties,
      these miRNAs may serve as novel biomarkers for this disease.

PMID- 28451400
TI  - Accumulation of GAS5 in exosomes is a marker of apoptosis induction.
AB  - Long non-coding RNAs (lncRNAs) are key regulatory molecules in many fundamental
      cellular processes and their deregulation is assumed to contribute to
      carcinogenesis. Exosomal lncRNAs are thought to be involved in the dissemination
      of cell signals to control local cellular microenvironments. In the current
      study, exosomal expression of growth arrest specific 5 (GAS5), an inhibitor of
      cell proliferation and promoter of apoptosis, was evaluated in apoptotic
      processes initiated by different mechanisms. Therefore, MCF-7 and MDA-MB-231
      breast cancer cells were treated with Taxol (2 and 10 nM) and bleomycin (2 and 10
      ng/ml) for 24 h. Following cell viability determination and measurement of
      apoptosis, cellular and exosomal expression levels of GAS5 were investigated
      using a quantitative polymerase chain reaction assay. The findings indicate that
      Taxol is more toxic than bleomycin at the indicated doses and the effect was more
      evident in the MCF-7 cells. Despite varying toxicity rates, comparable levels of
      apoptotic nucleosomes were measured between Taxol- and bleomycin-treated cells.
      Upon drug treatment, cellular expression levels of GAS rose (<=1.5-fold) in the
      two cell lines. It appears that even a small increase in cellular expression
      leads to exosomal enrichment, as the accumulation of GAS5 in exosomes was marked
      in the MCF-7 cells (<=5.8-fold). Compared with the MCF-7 cells, the extent of
      GAS5 enrichment in the exosomes secreted from MDA-MB-231 cells was moderate
      (<=1.9-fold), potentially as a result of reduced cell death. The present study
      indicates that GAS5 accumulation in exosomes is a prevalent event in apoptotic
      processes that are initiated by different mechanisms.

PMID- 28451401
TI  - In vivo detection of desmoplastic reaction using endocytoscopy: A new diagnostic
      marker of submucosal or more extensive invasion in colorectal carcinoma.
AB  - The pathological determination of desmoplastic reaction (DR) in colorectal
      carcinoma is useful for predicting extensive submucosal invasion. The aim of the
      present study was to determine the usefulness of endocytoscopy (EC) in detecting
      DR. A total of 72 cases of colorectal cancer with submucosal invasion (EC
      classification, EC3b) were evaluated. The utility of fine granular structure
      (FGS) observed via EC for the prediction of the presence of DR in the most
      superficial tumor layers was assessed. Of the 72 lesions, 26 were positive for
      FGS, and the majority of these lesions (23/26, 88.5%) exhibited a DR, indicating
      a significant association. The overall accuracy of the identification of FGS via
      EC that was predictive of a DR was 87.3%. The presence of FGS detected by EC was
      significantly associated with the presence of a DR, suggesting the clinical
      usefulness of EC in planning treatment for colon cancer with submucosal invasion.

PMID- 28451402
TI  - Efficacy and safety of antitumor agents plus radiotherapy compared with
      radiotherapy alone for brain metastases from lung cancer.
AB  - The present study aimed to investigate the efficacy and safety of different
      therapeutic regimens for brain metastases (BMs) from lung cancer (LC). A total of
      13 controlled trials (1,783 cases) involving chemotherapy, tyrosine kinase
      inhibitors or endostatin plus radiotherapy (combination group) vs. radiotherapy
      alone group were identified from PubMed. Compared with the radiotherapy alone
      group, the combination group resulted in a significant benefit for objective
      response rate (ORR) [risk ratio (RR), 1.38; 95% confidence interval (CI), 1.19
      1.60; P<0.0001], notably prolonged the time to central nervous system progression
      [CNS-TTP; hazard ratio (HR), 0.71; 95% CI, 0.57-0.90; P=0.004] and progression
      free survival (PFS; HR, 0.60; 95% CI, 0.44-0.83; P=0.002); however, failed in
      prolonging the overall survival (OS; HR, 0.80; 95% CI, 0.61-1.05; P=0.11) with a
      higher overall severe adverse events (AEs, Grade >=3; RR, 2.57; 95% CI, 1.24
      5.35; P=0.01). Notably, subgroup analysis demonstrated that targeted therapy plus
      radiotherapy possessed a superior OS compared with radiotherapy alone (HR, 0.58;
      95% CI, 0.37-0.90; P=0.01) with mild non-hematological toxicity and without
      severe hematotoxicity. The present study demonstrated that targeted agents plus
      radiotherapy possessed desirable effects with mild adverse events. Secondary to
      best, chemoradiotherapy is an alternative option for patients without suitable
      molecular targets.

PMID- 28451404
TI  - Primary cardiac lymphoma with unusual presentation: A report of two cases.
AB  - Primary cardiac tumors are rare, with an incidence of 0.056% according to autopsy
      reports. The most common type is myxoma, while other types, including sarcoma,
      lipoma, papillary fibroelastoma, rhabdomyoma, fibroma, hemangioma, teratoma,
      lymphoma and mesothelioma also occur. Primary cardiac tumors usually cause
      embolization, pericardial effusion and arrhythmia, leading to heart failure. Only
      10% of primary cardiac tumors are malignant, approximately 95% of which are
      sarcomas, while the remaining 5% are cardiac lymphomas and mesotheliomas. The
      present study reported a case of primary cardiac lymphoma (PCL) with bilateral
      renal involvement and a case of PCL with bilateral adrenal gland involvement. The
      prognosis of PCL is poor due to the low rate of early detection and treatment.
      The definitive diagnosis is dependent on pathology, and timely treatment with
      chemotherapy can be effective. The two cases developed life-threatening
      arrhythmia and responded to the initial chemotherapy. In the first case, complete
      remission was achieved after finalization of therapy. However, the second case
      refused further chemotherapy and succumbed to his condition after two months.

PMID- 28451403
TI  - Successful treatment with denosumab in a patient with sacral giant cell tumor of
      bone refractory to combination therapy with arterial embolization and zoledronic
      acid: A case report.
AB  - Giant cell tumor of bone (GCTB) is commonly treated with surgery; however,
      surgery of GCTB in the sacrum may be challenging due to the associated risk. A
      conservative approach may be selective arterial embolization or zoledronic acid
      (ZOL) treatment; however, there are currently no studies investigating the
      efficacy of combining these two treatments. Denosumab may also be used; however,
      to the best of our knowledge, there are no reports of a stepwise approach for the
      use of all three treatments in a single patient. We herein present such a case. A
      32-year-old woman diagnosed with sacral GCTB was treated with selective arterial
      embolization for 3 months. No improvement was observed, and monthly infusions of
      ZOL were added (administered 2 weeks after each arterial embolization treatment).
      Ten months after the initiation of ZOL, there was still no improvement. The
      therapy was changed to denosumab 120 mg, injected subcutaneously once a month. By
      the third dose, the buttock pain had decreased and the patient became ambulatory.
      At 5 and 10 months, computed tomography scans revealed bone sclerosis gradually
      appearing around the sacrum. By 1 year, needle biopsy detected no neoplastic
      cells. At that point, the patient discontinued treatment, as there was hepatic
      function impairment due to a history of hepatitis B. Despite treatment
      discontinuation, the patient exhibited no further symptoms, there were no signs
      of progression on radiography, and surgery was not required. Our patient
      experienced treatment failure with selective arterial embolization. The
      combination of ZOL with selective arterial embolization also did not improve the
      patient's condition. Denosumab was found to be superior to both treatments,
      achieving tumor remission. The patient remains symptom- and disease-free. Further
      studies are required, but our results suggest that patients with unresectable
      GCTB who fail to respond to selective arterial embolization may benefit from
      denosumab treatment, but not from combination therapy with selective arterial
      embolization and ZOL.

PMID- 28451405
TI  - Biliary intraductal papillary neoplasm with metachronous multiple tumors - true
      multicentric tumors or intrabiliary dissemination: A case report and review of
      the literature.
AB  - Intraductal papillary neoplasms of the bile duct (IPNBs) are recognized as a
      distinct type of biliary tumor. We herein discuss the possible mechanisms
      underlying the development of multiple tumors in patients with IPNBs through a
      case presentation and literature review. A 64-year-old woman initially underwent
      extended right hepatectomy for IPNB in the right hepatic duct. Although the
      surgical margin of the common bile duct was tumor-free, recurrence was detected
      in the intrapancreatic bile duct 26 months later. Both tumors had similar
      histopathological characteristics (intestinal-type IPNB with high-grade
      dysplasia, but no invasive cancer). A literature review identified 9 additional
      cases of multiple IPNBs. Unlike conventional IPNBs, which typically affect the
      intrahepatic or hilar bile duct, 80% of recurrent multiple tumors developed in
      the extrahepatic bile duct. Although multicentric tumors have been suggested in
      such cases, the intrabiliary dissemination of tumor cells appears to be more
      likely, as the majority of recurrent tumors develop in more distal parts of the
      bile duct compared with the primary tumor.

PMID- 28451406
TI  - Anaplastic astrocytoma cells not detectable on autopsy following long-term
      temozolomide treatment: A case report.
AB  - We herein present an autopsy case of a glioma patient who received long-term
      treatment with temozolomide (TMZ). The patient, a 35-year-old man with a
      hypointense tumor of the left frontal lobe, without contrast enhancement
      following gadolinium (Gd) administration on T1-weighted images, underwent tumor
      removal surgery, after which the tumor was diagnosed as anaplastic astrocytoma.
      By the third round of surgery, the tumor had progressed to anaplastic astrocytoma
      with contrast enhancement following Gd administration, and the patient received
      60 Gy of external beam radiotherapy and nimustine hydrochloride (ACNU)-based
      chemotherapy. After the fifth tumor removal surgery, TMZ was substituted with
      ACNU chemotherapy, which suppressed tumor progression. Following the 41st TMZ
      treatment, hemorrhage was observed in the residual tumor, and the hematoma had
      been replaced by a hemangioma. The hemangioma and surrounding brain tissue was
      removed during the sixth surgery. The patient survived for 14 years and 9 months
      after the initial surgery, but succumbed to hydrocephalus due to bleeding from
      hemangiomas. The histopathological specimens of the first to the sixth surgeries
      revealed mutant isocitrate dehydrogenase 1 (IDH1; R132H point mutation) and p53
      positive tumor cells, but cells positive for the R132H mutation or p53 could not
      be detected by immunohistochemistry in the autopsy specimens of the brain after
      108 courses of TMZ treatment. Mutant IDH1 (R132H) cells were also not detected in
      the autopsy specimens of the brain by polymerase chain reaction analysis.

PMID- 28451407
TI  - Rare giant primary ureteral polyp: A case report and literature review.
AB  - Primary ureteral fibroepithelial polyps (UFPs) are rare benign tumors of
      mesodermal origin. The majority UFPs are observed in the proximal part of the
      ureter and most commonly on the left side. The mean diameter of UFP is reported
      to be <5 cm. We herein present a rare case of a long primary ureteral polyp
      originating from the lower ureter in a 53-year-old woman. Following computed
      tomography, magnetic resonance imaging, retrograde pyelography and ureteroscopic
      examination, a preliminary diagnosis of giant primary lower ureteral polyp
      protruding into the bladder was obtained. Polyp resection and resection of the
      narrow ureteral segment with a V-shaped end-to-end anastomosis were performed.
      The length of this polyp was 15.0 cm, and the final pathological diagnosis was
      UFP. No recurrence or ureteral stenosis were observed at the 12-month follow-up.
      A supplementary review of previously published cases and related literature is
      also included.

PMID- 28451408
TI  - Incidence of carnitine deficiency in patients with cancer pain: A pilot study.
AB  - Carnitine deficiency is reportedly associated with increased pain sensation in
      diabetes mellitus and fibromyalgia, but the association between serum carnitine
      concentration and cancer pain has not been fully elucidated. We investigated the
      incidence of carnitine deficiency in patients with cancer pain, and examined the
      effect of the patients' demographic and clinical characteristics on pain
      intensity and carnitine deficiency. The serum carnitine concentration was
      measured in 50 patients with cancer pain receiving non-steroidal anti
      inflammatory drugs, but not opioids. Multivariate regression analysis was used to
      determine the association of carnitine concentration, pain intensity, age and
      gender with hemoglobin and C-reactive protein (CRP) concentrations. Carnitine
      deficiency was detected in 9 of the patients (18.0%) and found to be
      significantly correlated with an elevated CRP concentration (P=0.039). In
      conclusion, although there does not appear to be an association between carnitine
      deficiency and cancer pain, it may be affected by inflammation or infection.

PMID- 28451409
TI  - Clinical outcome and dose volume evaluation in patients who undergo brachytherapy
      for angiosarcoma of the scalp and face.
AB  - The present study was conducted to retrospectively evaluate survival and local
      control with definitive brachytherapy in patients with cutaneous angiosarcoma of
      the scalp and/or face, and to determine the optimal radiation dose and irradiated
      volume. Between November, 2009 and January, 2015, 9 consecutive patients with
      histologically proven angiosarcoma of the scalp and/or face who received image
      guided brachytherapy were retrospectively evaluated. The median age of the
      patients was 83.4 years (range, 67.7-91.9 years). Of the 9 patients, 8 had no
      lymph node metastasis and 1 patient had cervical lymph node metastasis. The
      patients were irradiated with a dose of 3 Gy three times per week for varying
      lengths of time; 4 patients received a total dose of 60 Gy, 1 received 48 Gy and
      the 4 remaining patients received 45 Gy. The patient who received 48 Gy also
      underwent additional electron therapy of 16 Gy in 8 fractions. The overall
      survival, progression-free survival and local progression-free rates at 3 years
      were 50.8% [95% confidence interval (CI): 15.6-78.1%], 37.0% (95% CI: 6.8-69.3%)
      and 77.8% (95% CI: 36.5-93.9%), respectively. The local progression-free rate in
      the 4 patients who received a total of >=60 Gy was statistically significantly
      better compared with that in the 5 patients who received a dose of <60 Gy
      (P=0.027). A total of 7 patients had grade 2 radiation dermatitis, whereas the
      remaining 2 patients had grade 3 dermatitis. All the patients had grade 2
      alopecia. Local disease control achieved by radiotherapy resulted in higher
      survival. Therefore, prescribing >=60 Gy in 20 fractions for the gross tumor
      volume is recommended for angiosarcoma of the scalp and face.

PMID- 28451410
TI  - Doceaqualip in a patient with prostate cancer who had an allergic reaction to
      conventional docetaxel: A case report.
AB  - Docetaxel has been widely used in the treatment of several cancers, including
      adenocarcinoma of the prostate gland. As docetaxel is insoluble in water, it must
      be administered with polysorbate 80 and ethanol, which are known to cause
      hypersensitivity reactions. Premedication with corticosteroids and antihistamines
      is advocated prior to docetaxel administration; however, toxicities, occasionally
      fatal, have been reported, even with corticosteroid premedication. We herein
      report the case of a patient with adenocarcinoma of the prostate, with bone
      metastasis and an Eastern Cooperative Oncology Group performance status of <2,
      who developed an allergic reaction to conventional docetaxel (Taxotere), despite
      being premedicated with corticosteroids and antihistamines. The patient was
      managed with corticosteroids and antihistamines, and was later started on
      Doceaqualip, a nanosomal docetaxel lipid suspension. Doceaqualip was well
      tolerated by the patient and 5 cycles were subsequently administered, without any
      adverse reactions. Adenocarcinoma also regressed, as evidenced by positron
      emission tomography/computed tomography.

PMID- 28451411
TI  - Diffusion-weighted magnetic resonance imaging for the detection of metastatic
      lymph nodes in patients with lung cancer: A meta-analysis.
AB  - The aim of the present meta-analysis was to evaluate the diagnostic value of
      diffusion-weighted imaging (DWI) in differentiating metastatic from non
      metastatic lymph nodes in patients with lung cancer. A systematic literature
      search was performed to identify eligible original studies. The quality of
      included studies was assessed using 'quality assessment of diagnostic accuracy
      studies' (QUADAS-2). Meta-analysis was performed to pool sensitivity and
      specificity, to calculate the positive likelihood ratio (PLR), the negative
      likelihood ratio (NLR) and the diagnostic odds ratio (DOR), and to construct the
      summary receiver operating characteristic (SROC) curve. The homogeneity,
      threshold effect and publication bias were also investigated. Meta-regression
      analysis was performed to identify the sources of heterogeneity. A total of 10
      studies with 11 datasets met the inclusion criteria, which comprised 796 patients
      with a total of 2,433 lymph nodes. The pooled diagnostic sensitivity was 0.78
      [95% confidence interval (CI): 0.74-0.81] and the pooled diagnostic specificity
      was 0.88 (95% CI: 0.86-0.89). The PLR, NLR, and DOR were 7.11 (95% CI: 4.39
      11.52), 0.24 (95% CI: 0.18-0.33), and 31.14 (95% CI: 17.32-55.98), respectively.
      The area under the SROC curve was 0.90. No publication bias was found (bias=
      0.15, P=0.887). Notable heterogeneity was, however, observed, and patient
      selection, type of lung cancer, number of enrolled lymph nodes, reference
      standard, B-value and the type of scanner were the sources of heterogeneity
      (P<0.05). No significant threshold effect was identified (P=0.537). In
      conclusion, DWI has been revealed to be a valuable magnetic resonance imaging
      (MRI) modality, with good diagnostic performance for distinguishing metastatic
      from non-metastatic lymph nodes in patients with lung cancer. Therefore, DWI may
      be a useful supplement to conventional MRI techniques.

PMID- 28451412
TI  - Observational study of colonoscopy techniques used for acute colorectal
      obstruction: A single-center experience.
AB  - The prevalence of acute colorectal obstruction at the hospital setting is high.
      There is need for improvement in the quality of colonoscopy for relieving
      obstruction. A retrospective, uncontrolled, open-label study was conducted, with
      the aim of documenting the causes of acute colorectal obstruction and the quality
      of colonoscopy practice in managing obstruction at a university hospital in
      China. A total of 61 adult patients with acute colorectal obstruction treated
      with urgent colonoscopy between February, 2011 and January, 2016 were identified
      at the Endoscopic Unit of Tongji Hospital (Wuhan, China). The technique success
      rate was the primary outcome. The etiology was mainly related to malignant
      diseases, including colorectal cancer in 53 patients (86.9%) and advanced
      peritoneal serous carcinoma leading to extrinsic colonic compression in 1 patient
      (1.6%). Benign causes of obstruction included foreign bodies in 3 patients (4.9%)
      and fecal impaction in 2 patients (3.3%); furthermore, anastomotic strictures
      were found in 2 patients (3.3%). The technique success rate was 98.4% (60/61).
      All colorectal cancer patients who underwent urgent colonoscopy were admitted to
      the Department of Surgery for placement of a self-expanding metallic stent; 1
      patient who had an extracolonic malignancy underwent placement of a transanal
      colonoscopic decompression tube as palliative therapy and 2 patients with
      anastomotic strictures underwent endoscopic balloon dilation. Furthermore,
      colonoscopy was used for extracting the foreign body, as well as removing fecal
      stones in all the patients. In conclusion, urgent colonoscopy as a minimal
      invasive approach is associated with certain advantages for diagnosing and
      managing acute colorectal obstruction. Furthermore, experienced operators
      achieved a better outcome when managing colorectal obstruction.

PMID- 28451413
TI  - A case of metastatic Xp11.2 translocation renal cell carcinoma successfully
      managed by cytoreductive nephrectomy followed by axitinib therapy.
AB  - Targeted medications for metastatic adult Xp11.2 translocation renal cell
      carcinoma (RCC) remain to be identified. We herein report a case of metastatic
      Xp11.2 translocation RCC controlled with cytoreductive nephrectomy (CN) and
      axitinib therapy. A 57-year-old woman complained of fatigue and low back pain.
      Imaging studies revealed a right renal tumor, with multiple lung and mediastinal
      lymph node metastases. Although the patient received 10 mg axitinib therapy for 5
      months at the hospital she was initially admitted to, the size of the primary and
      metastatic lesions was not reduced. Thus, she was referred to the Tokyo Women's
      Medical University Hospital (Tokyo, Japan) for further treatment, where she
      underwent CN. On macroscopic examination, almost the entire kidney was replaced
      by a yellowish brown tumor >80 mm in diameter. Immunohistochemical examination
      confirmed the diagnosis of Xp11.2 translocation RCC. One month after surgery,
      axitinib therapy was resumed and the size of the metastatic lesions gradually
      decreased. These findings suggest that axitinib therapy is effective for adult
      Xp11.2 translocation RCC.

PMID- 28451414
TI  - Response to regorafenib at an initial dose of 120 mg as salvage therapy for
      metastatic colorectal cancer.
AB  - Regorafenib (Reg) is an oral multikinase inhibitor that has achieved improved
      overall survival in patients with metastatic colorectal cancer (mCRC) in the
      salvage therapy setting. However, Reg is difficult to manage and determine the
      optimal dose due to adverse events (AEs). The objective of this study was to
      retrospectively evaluate the clinical benefit and determine the optimal dose of
      Reg in mCRC patients. A total of 20 mCRC patients were enrolled in this
      retrospective study. Initially, 8 patients who received a starting dose of 160 mg
      Reg (160 mg group) once a day were evaluated; however, they were unable to
      continue with the initial dose of 160 mg due to grade 3 adverse events (AEs),
      such as hand-foot skin reaction (HFSR) and small intestinal hemorrhage.
      Furthermore, 2 of the 8 patients refused subsequent treatment due to HFSR and the
      remaining 6 patients received a dose reduction from 160 to 120 mg Reg. A reduced
      dose of 120 mg Reg was also assessed with our dose modification method in 12
      patients (120 mg group). The optimal response of the 160 and 120 mg group
      patients was 0.0 and 8.3% (1/12), respectively. In the 160 mg group, 3 patients
      exhibited stable disease (SD). Surprisingly, among the the 120 mg group patients
      1 exhibited partial response (PR) and 6 had SD. The PR case displayed shrinkage
      of the local recurrence and morphological changes. One of the SD cases exhibited
      formation of a cavity in the lung metastasis, with intralesional morphological
      changes of the liver metastasis. The duration of the treatment in the PR case and
      the SD case with the cavitation was 6.5 months (9 cycles) and 5 months (6
      cycles), respectively. The median progression-free survival (PFS) was 77 days
      (range, 30-230+ days) and the median overall survival (OS) was 204 days (range,
      53-511+ days). The final date of the follow-up period was July 31, 2016. The 160
      mg group was associated with a 25% (3/8) incidence of HFSR, 12.5% (1/8) of small
      intestinal hemorrhage and 12.5% (1/8) of anemia and thrombocytopenia; the AEs
      were grade >3. The 120 mg group was associated with an incidence of only 8.3%
      (1/12) of grade >3 hypertension. Thus, the 120 mg group experienced lower
      treatment-related toxicity compared with the 160 mg group. Despite a reduced
      initial dose of Reg, a significant effect was observed, with 1 PR and 6 favorable
      SD cases, with good tolerability. Therefore, an initial dose modification of 120
      mg Reg is recommended as an alternative strategy for the treatment of mCRC in the
      salvage setting.

PMID- 28451415
TI  - A retrospective clinical analysis of 5 cases of vaginal melanoma.
AB  - Vaginal melanoma is a rare tumor, accounting for <1% of all melanomas and ~1-5%
      of all vaginal malignant tumors. The prognosis of vaginal melanoma is extremely
      poor, as it is often resistant to chemotherapy and radiotherapy, and metastases
      may develop in the early stages of the disease. The present study investigated 5
      patients with vaginal melanoma treated at the Department of Gynecology of Osaka
      City University Hospital (Osaka, Japan) between October, 2000 and April, 2014.
      All the cases presented with abnormal genital bleeding as the main complaint.
      Notably, in 3 of the 5 cases the tumors appeared as non-pigmented polyps. Local
      resection was performed as the primary treatment in all 5 cases. After surgery,
      dermal injection of interferon beta (feron maintenance therapy) was performed in
      3 cases, and dacarbazine, nimustine, vincristine and interferon beta (DAVFeron
      therapy) was administered in 1 case as adjuvant therapy. All 5 cases recurred
      within 1 year. The site of recurrence varied, and included the vaginal wall,
      liver, brain and lung. The median overall survival was 419 days and the median
      progression-free survival 177 days. In this cohort, all the cases presented with
      abnormal genital bleeding as the main complaint. Therefore, malignant melanoma of
      the vagina must be considered along with other gynecological malignancies in
      patients with abnormal genital bleeding. In this study, over half of the cases
      had a non-pigmented polypoid lesion of the vagina. Therefore, malignant melanoma
      of the vagina must be considered when a polypoid lesion is identified on the
      vaginal wall.

PMID- 28451416
TI  - Laparoscopic local extraperitoneal para-aortic lymphadenectomy: Description of a
      novel technique.
AB  - The aim of the present study was to introduce and describe a novel technique,
      which has been termed 'laparoscopic local extraperitoneal para-aortic
      lymphadenectomy', and to evaluate its feasibility and safety. In this
      retrospective case study, a series of 21 patients were selected who underwent
      laparoscopic local extraperitoneal para-aortic lymphadenectomy for gynecological
      malignancies between March and August 2014 at the Obstetrics and Gynecology
      Hospital of Fudan University, Shanghai, China. All the surgical procedures were
      performed by the same operational team. Patients' data were collected
      retrospectively, and the characteristics included patient age, body mass index
      (BMI), tumor stage, tumor grade, blood loss, operative time (laparoscopic local
      extraperitoneal para-aortic lymphadenectomy), length of hospital stay,
      intraoperative and postoperative complications, pathology, lymph node count and
      lymph node status. A total of 21 patients underwent laparoscopic local
      extraperitoneal para-aortic lymphadenectomy. The median patient age was 52 years
      (range, 45-71 years); the median BMI was 24.8 kg/m2 (range, 22.2-32.4 kg/m2); the
      median operating time for the para-aortic lymphadenectomy was 70 min (range, 58
      95 min); and the median estimated blood loss of the total surgery was 200 ml
      (range, 100-600 ml). No patient required a blood transfusion during the
      operation. The median length of hospital stay was 7 days (range, 5-9 days), and
      the median number of para-aortic lymph nodes was measured as 12 (range, 7-17).
      Postoperative complications included one patient with chylous ascites, who
      responded to conservative management with intravenous somatostatin. In
      conclusion, the present study has demonstrated that laparoscopic local
      extraperitoneal para-aortic lymphadenectomy, which avoids interference of the
      bowels during surgery, is safe and practical.

PMID- 28451417
TI  - Proteus syndrome: A case report and review of the literature.
AB  - Proteus syndrome is a rare complex syndrome involving clinical presentation with
      atypical skeletal growth. Only a limited number of cases with this syndrome have
      been reported in the literature to date. We herein report the case of a Chinese
      male patient with Proteus syndrome and review the clinical and molecular
      characteristics of this disease. The patient was a 34-year-old man with clinical
      manifestations suggestive of the Proteus syndrome, including mosaic distribution
      of the lesions, sporadic occurrence, progressive course, disproportionate
      overgrowth of the legs, epidermal nevi, lipomas, venous malformations and
      characteristic facial phenotype. Genetic mosaicism, such as mutations involving
      the phosphoinositide 3 kinase-AKT pathway in the affected tissues, may be
      important causes of Proteus syndrome. In the present case, samples from the
      affected tissues were collected from the patient and were further analyzed using
      whole-exome sequencing. However, no mutation of the genes reportedly associated
      with Proteus syndrome was identified in the affected tissues. Proteus syndrome is
      a complex mosaic disorder with a number of variable characteristics. Although
      activating AKT1 mutations have been found to be associated with this disorder,
      the molecular etiology remains to be fully elucidated and diagnostic criteria
      must be established in the clinical setting.

PMID- 28451419
TI  - Sudden cardiac death in a patient with advanced hepatocellular carcinoma with
      good response to sorafenib treatment: A case report with literature analysis.
AB  - Hepatocellular carcinoma (HCC) is the principal primary liver tumor, representing
      the third largest cause of cancer-associated death worldwide. The actual
      reference standard systemic treatment for advanced HCC is represented by
      sorafenib, a multi-targeted orally active small-molecule tyrosine kinase
      inhibitor. Sorafenib has exhibited a good general safety profile in multiple
      clinical trials. However, adverse drug-associated events are common, occasionally
      severe, and special attention should be paid to cardiovascular adverse events,
      particularly in patients with risk factors or known heart disease. In the present
      study, the case of a patient with no known cardiovascular risk factors affected
      by highly enhancing advanced HCC in cirrhotic liver, who died during successful
      sorafenib monotherapy, is reported.

PMID- 28451418
TI  - Southwestern Oncology Group pretreatment risk criteria as predictive or
      prognostic factors in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a clonal hematological malignant condition and
      the implications of pretreatment risk criteria as predictive or prognostic
      factors are constantly under evaluation. With this study, the authors' intent was
      to characterize AML patients and to evaluate the clinical outcome associated with
      Southwestern Oncology Group (SWOG) coding pretreatment risk criteria/cytogenetic
      score. Between 2002 and 2010, 225 patients were diagnosed with AML at the
      Portuguese Institute of Oncology (Porto, Portugal). From this patient group, 128
      patients aged <65 years were selected. The patients were treated using a
      combination of cytarabine and anthracycline, with the addition of cyclosporine
      when bone marrow dysplasia was observed. A median survival of 24 months was
      observed in this group. The patients were divided in subgroups according to the
      SWOG pretreatment risk criteria. We observed a statistically significant
      association of non-favorable SWOG coding with female gender [P=0.025; risk ratio
      (RR)=3.632, 95% confidence interval (CI): 1.113-11.852], indication for
      allogeneic bone marrow transplantation (P=0.023, RR=1.317, 95% CI: 1.184-1.465),
      complete response achievement (P=0.013, RR=1.385, 95% CI: 11.232-1.556) and
      relapse (P=0.048, RR=3.181, 95% CI: 10.966-10.478). Furthermore, SWOG
      pretreatment risk criteria also significantly affected global overall survival
      (OS; P=0.003) and OS at 5 years (P=0.001). A multivariate Cox regression analysis
      supported response to induction therapy (3-year OS: P=0.011, RR=0.385, 95% CI:
      10.184-0.806; 5-year OS: P=0.012, RR=0.388, 95% CI: 10.597-1.994), consolidation
      (3-year OS: P=0.005, RR=0.328, 95% CI: 0.150-0.720; 5-year OS: P=0.002, RR=0.308,
      95% CI: 0.144-0.657) and the diagnosis of therapy-related aml (3-year OS:
      P=0.016, RR=2.756, 95% CI: 0.486-1.281; 5-year OS: P=0.031, RR=2.369, 95% CI:
      1.081-5.189) as prognostic factors, but this was not confirmed for SWOG
      pretreatment risk criteria. Therefore, we concluded that the reproducibility of
      the application of the SWOG pretreatment risk criteria may not be available as a
      prognostic factor in every acute leukemia population. However, its application as
      a predictive factor of response has been confirmed in our population.

PMID- 28451420
TI  - Feasibility study to evaluate compliance of physical activity over a long time
      period and its influence on the total activity score, glucose metabolism and
      physical and psychological parameters following breast cancer.
AB  - Despite recommendations that patients with breast cancer ought to undertake
      physical exercise, a majority of breast cancer patients fail to change their
      lifestyle and to increase their physical activity following diagnosis. In this
      clinical intervention feasibility study, compliance and sustainability of a
      walking training program over 24 weeks in patients with breast cancer following
      treatment were examined. The endpoints were retention rates after 12 and 24 weeks
      (6 months) and serum levels of glucose metabolism, the total activity score,
      endurance, a subjectively perceived exertion-during-endurance stress test,
      quality of life and fatigue. A supervised walking training session for 60-75 min
      twice-weekly over 6 months in 35 patients with breast cancer following treatment
      was examined. The study retention at 12 weeks was 27/35 (77%), and at 24 weeks
      24/35 (69%). After 24 weeks, the glycated hemoglobin (HbA1c) score was
      significantly lowered following the intervention (P=0.001). Insulin and glucose
      levels remained unchanged. Significant improvements were measured in the
      patients' body mass index (P=0.001), endurance (P=0.013) and in psychological
      parameters such as fatigue (P=0.008) and the quality of life (P=0.007).
      Furthermore, the patients exhibited significant improvements in their
      subjectively perceived exertion during an endurance-stress test (P=0.079) and in
      their total activity score (P=0.931). The present study demonstrated an increase
      in total activity resulting from the supervised walking training program twice
      weekly over 6 months. Significant changes in long-term parameters of glucose
      metabolism, such as in the HbA1c score, also occurred. Furthermore, significant
      improvements in physical and psychological parameters were observed.

PMID- 28451421
TI  - Role of RAS mutation status as a prognostic factor for patients with advanced
      colorectal cancer treated with first-line chemotherapy based on fluoropyrimidines
      and oxaliplatin, with or without bevavizumab: A retrospective analysis.
AB  - The role of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma
      RAS viral oncogene homolog (NRAS) mutations as negative predictors for anti
      epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer
      (CRC) has been firmly established. However, whether the RAS mutation status plays
      a role as a biomarker for anti-vascular endothelial growth factor (VEGF)
      treatment remains controversial. Data from 93 CRC patients who received first
      line cytotoxic chemotherapy with fluoropyrimidines and oxaliplatin, with or
      without bevacizumab, were analyzed. We investigated the association between the
      RAS mutation status and clinical outcomes in terms of response rate, progression
      free survival (PFS) and overall survival (OS). Mutations in RAS genes were
      observed in 47 (52.6%) patients (45 KRAS and 2 NRAS mutations). Patients with
      tumours harbouring RAS mutations were less suitable for primary tumour resection,
      were more likely to develop lung metastases, and received bevacizumab treatment
      for a shorter time period compared with those with wild-type tumours. The
      response rate to chemotherapy did not differ according to the RAS mutation
      status, and there were no significant differences in PFS [RAS mutation: 12
      months, 95% confidence interval (CI): 8.7-15.2 vs. RAS wild-type: 12 months, 95%
      CI: 9.67-14.32; P=0.857] or OS (RAS mutation: 20 months, 95% CI: 14.3-25.6 vs.
      RAS wild-type: 24 months, 95% CI: 18.7-29.2; P=0.631). Patients with RAS mutation
      vs. those with RAS wild-type exhibited a favourable trend in PFS when treated
      with bevacizumab (13 months, 95% CI: 6.5-19.4 vs. 10 months, 95% CI: 4.2-15.7,
      respectively; P=0.07) and OS (27 months, 95% CI: 18.5-35.4 vs. 15 months, 95% CI:
      12.4-17.5, respectively; P=0.22). In conclusion, RAS mutations are not a
      prognostic marker for PFS and OS in CRC patients receiving fluoropyrimidine
      oxaliplatine treatment, with or without bevacizumab. RAS mutations are not
      predictive of the lack of efficacy of bevacizumab, and these patients appear to
      benefit from anti-angiogenic treatment.

PMID- 28451423
TI  - Pilomatrix carcinoma: More malignant biological behavior than was considered in
      the past.
AB  - Pilomatrix carcinoma is a very rare malignancy, with ~130 cases reported in the
      literature. In the past, pilomatrix carcinoma was considered to be a low-grade
      malignant tumor. Currently, however, its significant recurrence and metastatic
      potential has been well documented. Lymph node and systemic metastases are
      frequently observed. Wide surgical excision of the primary lesion is the
      principal modality of treatment, whereas adjuvant radiotherapy may be beneficial
      in local tumor control. Lymph node metastases may be treated surgically or with
      radiotherapy. Systemic disease is not responsive to chemotherapy, and is hence
      associated with a poor prognosis. Since the majority of nodal and systemic
      metastases present after the initial diagnosis and treatment, follow-up
      examinations of these patients may be warranted, despite the currently inadequate
      treatment options. In the present study, a case of pilomatrix carcinoma of the
      parotid region with early local recurrence only 2 months after complete excision
      with negative surgical margins is reported. The local recurrence was treated by
      excision and radiotherapy. The associated literature is also discussed.

PMID- 28451422
TI  - Erlotinib as second- or third-line treatment in elderly patients with advanced
      non-small cell lung cancer: Keio Lung Oncology Group Study 001 (KLOG001).
AB  - The aim of this study was to assess the efficacy and safety of erlotinib, an
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as
      second- or third-line treatment for elderly Japanese patients with non-small-cell
      lung cancer (NSCLC). The patients eligible for this phase II trial were aged >=70
      years, had stage III/IV or recurrent NSCLC, and had previously received 1 or 2
      chemotherapy regimens that did not include EGFR-TKIs. The patients received
      erlotinib at a dose of 150 mg/day. The primary endpoint was overall response rate
      (ORR), and the secondary endpoints were progression-free survival (PFS), overall
      survival (OS) and toxicity. A total of 38 patients with a median age of 76 years
      were enrolled. The majority of the patients were men (66%), had an Eastern
      Cooperative Oncology Group performance status of 1 (58%), stage IV disease (66%)
      and adenocarcinoma (74%). Of the 35 patients, 13 (34%) had tumors with EGFR
      mutations. The ORR was 26.3% (95% confidence interval: 12.1-40.5%) and the
      disease control rate was 47.4%. The median PFS was 3.7 months and the median OS
      was 17.3 months. The grade 3 adverse events observed included rash (13%),
      diarrhea (5%), interstitial pneumonitis (5%), anorexia (3%) and gastrointestinal
      bleeding (3%). Grade 4 or 5 adverse events were not observed. The median OS did
      not differ significantly between patients aged <75 years (14.9 months) and those
      aged >=75 years (19.0 months; P=0.226). Therefore, erlotinib was found to be
      effective and well-tolerated in elderly patients with previously treated NSCLC.

PMID- 28451424
TI  - Parosteal ossifying lipoma of the clavicle: A case report.
AB  - Lipomas are very common benign adipose tissue tumors that most often develop in
      subcutaneous tissue. A limited number of studies have described the
      characteristics of parosteal ossifying lipomas located in the fibula, cervical
      vertebrae and mandible. However, to the best of our knowledge, parosteal
      ossifying lipoma of the clavicle has not yet been reported. We herein describe
      the clinical symptoms, radiological and histological findings in a rare case of
      parosteal ossifying lipoma of the clavicle in a 40-year-old male patient. The
      characteristic histological appearance, together with computed tomography and/or
      magnetic resonance imaging characteristics, should aid in the accurate diagnosis
      of such cases.

PMID- 28451425
TI  - Non-small-cell lung cancer metastasis to the oral cavity: A case report.
AB  - We herein report an unusual occurrence of lung cancer metastasis to the oral
      cavity, reflecting the progression of the primary malignancy. A biopsy of oral
      lesions should always be performed, even of those located in uncommon sites, in
      patients with a history of uncontrolled lung cancer. Although this is a rare
      occurrence, our patient exhibited characteristics suggestive of oral metastasis
      from lung cancer, namely presence of lung adenocarcinoma, development of oral
      metastasis during the clinical course of the disease, accompanying multiple
      metastatic lesions, including to the brain and abdomen, and rapid fatal
      progression after the manifestation of oral metastasis. It is important to
      acknowledge the possibility of metastasis to the oral cavity in lung cancer
      patients with extensive metastases. Prompt diagnosis by biopsy of the lesion is
      required to establish the correct diagnosis.

PMID- 28451426
TI  - Sole metastatic pulmonary nodules from breast cancer simulating primary lung
      adenocarcinoma: Two case reports.
AB  - The characteristic radiological signs of primary lung adenocarcinoma include
      notching, lobulation, spicular formation, pleural indentation and a bronchus
      leading to the nodule (bronchus sign). However, metastatic tumors rarely display
      such characteristics. We herein present two cases of breast cancer with sole
      metastatic pulmonary tumors recurring ~20 years after surgery for breast cancer.
      These patients exhibited radiographic signs specific to primary lung
      adenocarcinoma. Pulmonary metastatic nodular lesions occur through hematogenous
      spread; therefore, obtaining pathological specimens by transbronchial biopsy may
      be challenging. In our patients, however, obtaining pathological specimens by
      transbronchial biopsy was feasible and it ultimately confirmed the diagnosis of
      lung metastasis from previously treated breast cancer. To the best of our
      knowledge, no similar cases are reported in the English medical literature.
      Therefore, metastatic breast cancer may exhibit the characteristic radiological
      signs of pulmonary lung adenocarcinoma and, although rare, pulmonary metastasis
      from breast cancer should be considered even in the presence of irregularly
      shaped pulmonary nodule(s) following long-term disease-free survival.

PMID- 28451427
TI  - External beam radiation for the treatment of castration-resistant prostate cancer
      following primary hormonal therapy with androgen ablation: Analysis and outcome
      of 21 patients.
AB  - Patients who undergo early androgen-deprivation therapy for prostate cancer may
      eventually develop castration-resistant prostate cancer. However, no optimal
      treatment for non-metastasized castration-resistant prostate cancer has yet been
      established. In the present retrospective, single-institutional study, the
      radiotherapy (RT) outcomes were evaluated in patients who underwent androgen
      deprivation therapy for non-metastatic prostate cancer and subsequently developed
      castration-resistant disease. Following a thorough chart review, the data of 21
      patients with castration-resistant prostate cancer who were treated between 2000
      and 2010 with external beam radiation therapy (EBRT) at a prostate radiation dose
      of >45 Gy were evaluated. Of the 21 patients, 16 (76%) developed biochemical
      recurrence after RT, with a mean time to biochemical recurrence of 17 months. A
      total of 18 patients succumbed to the disease during follow-up, with a mean
      survival of 3 years after RT. A radiation dose of >66 Gy was associated with a
      longer time to biochemical recurrence after RT (P=0.011) and a longer survival,
      compared with a dose of <=66 Gy (P=0.028). The mean overall survival time after
      RT was 42 months and did not depend on the primary hormonal treatment. Prostate
      specific survival time was negatively associated with the Gleason score at
      diagnosis. The prostate-specific antigen (PSA) concentration prior to RT was a
      prognostic factor for biochemical recurrence of prostate cancer after RT, as well
      as for prostate cancer-specific survival. Finally, the multivariate analysis
      revealed that age, PSA concentration prior to RT and a high Gleason score were
      independent prognostic factors for prostate cancer-specific survival. Overall,
      our study findings demonstrated that disease progression was common after EBRT
      for castration-resistant prostate cancer and that survival was limited. However,
      young patients and those with low-risk disease at the time of diagnosis may
      benefit from RT.

PMID- 28451428
TI  - Invasive mucinous adenocarcinoma of the lung presenting as a large, thin-walled
      cyst: A case report and literature review.
AB  - Invasive mucinous adenocarcinoma (IMA), formerly referred to as mucinous
      bronchioloalveolar carcinoma, is a rare variant form of invasive adenocarcinoma
      and is radiologically characterized by dense pneumonic consolidation, ground
      glass opacity and nodules. By contrast, large, thin-walled cysts are rare. We
      herein report the case of a 75-year-old man with IMA presenting as a large,
      irregularly shaped cystic lesion. The histological diagnosis was based on
      specimens obtained during a bronchoscopy. The patient underwent lobectomy
      followed by anticancer chemotherapy for residual intrapulmonary metastases. Of
      note, the small metastatic nodules transformed into cystic lesions with thin
      walls and fused, forming a large, multiloculated cystic lesion. Typical pneumonic
      consolidation appeared in the pericystic parenchyma later during the clinical
      course. The available literature on this rare radiological manifestation was also
      reviewed and discussed. Clinicians should be aware of thin-walled cystic lesions
      as they may be an unusual radiological finding in IMA.

PMID- 28451429
TI  - Current management of liposarcoma of the spermatic cord: A case report and review
      of the literature.
AB  - Liposarcomas of the spermatic cord, a rare cause of an inguinal mass, may closely
      mimic inguinal hernias on clinical examination. However, these tumors require a
      different surgical approach and treatment plan; therefore, intraoperative
      diagnosis might complicate patient management. We report the case of a 63-year
      old man who presented with a mobile mass in the inguinal canal consistent with an
      inguinal hernia. The patient was subsequently diagnosed with a liposarcoma of the
      spermatic cord and successfully treated with extensive local resection, including
      radical orchiectomy and en bloc resection of the mass and associated cord
      structures. No adjuvant therapy was deemed necessary, and the patient remained
      asymptomatic and disease-free 10 years after surgery. The details of this case
      are presented, along with a review and discussion of the currently available data
      regarding the diagnosis and management of this challenging condition.

PMID- 28451430
TI  - Efficacy of metformin for advanced-stage endometrial cancer: A case report.
AB  - The paradigm of obesity, diabetes mellitus and insulin resistance possibly plays
      a critical role in the pathogenesis of endometrial cancer (EC). Impaired glucose
      tolerance and insulin resistance may play a direct or facilitating role in the
      neoplastic transformation of the endometrium, whereas antidiabetic therapy,
      particularly with metformin, has been suggested to inhibit EC progression. We
      herein present the case of a patient with EC who received metformin monotherapy
      due to complications after undergoing surgery. At 45 months after the
      introduction of metformin treatment, the patient had no complaints and continued
      receiving metformin without signs of tumor recurrence. As metformin is widely
      used among diabetic patients and in ongoing clinical trials in cancer patients,
      the aforementioned results deserve further clinical investigation.

PMID- 28451431
TI  - Resection of upper lip adenoid cystic carcinoma and reconstruction with reverse
      Yu flap: Report of three cases and a literature review.
AB  - The present study aimed to describe the techniques that were used, and the
      results obtained, with the reverse Yu flap to reconstruct medium-sized upper lip
      defects following resection for adenoid cystic carcinoma (ACC). Data concerning
      the clinical and pathological characteristics of tumours, the size and location
      of the defects, surgical resection and the reconstructive procedure used were
      evaluated in three patients, as well as postoperative complications and outcomes.
      In all cases, a complete surgical removal of ACC was achieved with clear margins
      of at least 1 cm. Histopathological features revealed two cases with a
      predominant solid growth pattern, and one case of cribriform. Following tumour
      excision, the average size of the upper lip defect was 35.7*30 mm. The reverse Yu
      flap was raised simultaneously with tumour resection in all cases. No flap
      failed, and both excellent aesthetic and functional results were obtained. All
      the patients had a satisfactory oral competence, without microstomia, after a
      median of 20 months follow-up (range, 12-30 months). Adjuvant radiation therapy
      was not necessary in any case. On the basis of the present case study and
      literature review, reverse Yu flap is revealed to be a simple and reliable
      technique for the reconstruction of defects ranging from one-third to two-thirds
      of the total upper lip length, involving the commissure, nasolabial fold and
      philtrum, with minimal donor morbidity and a good functional and aesthetic
      outcome. This flap appears to be a valid surgical option for reconstruction of
      medium-sized upper lip defects, which may be considered following radical
      excision of ACC.

PMID- 28451432
TI  - The social facilitation of eating or the facilitation of social eating?
AB  - People eat more when they eat in groups. Various explanations have been offered
      for this "social facilitation" of eating. We consider these explanations and find
      most of them wanting, especially insofar as they do not take into account the
      increased per capita provision of food when people eat together. We suggest that
      people often prefer to eat in groups precisely because it offers them an
      opportunity to overindulge.

PMID- 28451433
TI  - Lenalidomide-induced eosinophilic pneumonia.
AB  - Multiple myeloma is a plasma cell dyscrasia accounting for 10% of haematologic
      malignancies. Lenalidomide is an immunomodulatory drug analogous to thalidomide
      that is approved for use in patients with myelodysplastic syndrome, and in
      combination with dexamethasone for refractory or relapsed multiple myeloma.
      Lenalidomide is preferred to thalidomide because of reduced toxicity, and
      pulmonary side effects are considered rare. We present, to our knowledge, an
      unusual and first reported case of a patient with relapsed multiple myeloma who
      received lenalidomide after autologous stem cell transplant, then developed
      eosinophilic pneumonia presenting as dyspnoea, peripheral eosinophilia, and
      bilateral pulmonary opacities. Bronchoscopy with bronchoalveolar lavage was
      negative for infection, and transbronchial lung biopsies showed eosinophilic
      pneumonia. After discontinuation of lenalidomide and initiation of prednisone
      therapy, his dyspnoea improved and eosinophilia resolved; however, symptoms
      recurred when the drug was restarted at a lower dose, confirming its causative
      role. In the absence of infection, clinicians should always bear in mind drug
      toxicity in the differential diagnosis of patients receiving lenalidomide and
      related agents.

PMID- 28451434
TI  - A few long versus many short foraging trips: different foraging strategies of
      lesser kestrel sexes during breeding.
AB  - BACKGROUND: In species with biparental care both members of the breeding pair
      cooperate to raise the offspring either by assisting each other in every
      reproductive task or by specializing in different ones. The latter case is known
      as reproductive role specialization. Raptors are considered one of the most role
      specialized groups, but little is known about parental behavior away from the
      nest. Until the advent of biologgers, avian role specialization was traditionally
      studied with direct observations at the nest because of the difficulties of
      following and recording the behavior of free-ranging individuals. In this paper
      we analyze how the role specialization of the lesser kestrel (Falco naumanni)
      influences foraging movement patterns throughout the breeding season. We tracked
      30 lesser kestrel breeders from two breeding colonies using high-frequency GPS
      dataloggers during four consecutive breeding seasons. RESULTS: We found no
      differences between sexes in lesser kestrel foraging movements early in the
      breeding season before the formation of the breeding pair. However, we observed
      sexually distinct foraging movement strategies later in the breeding season once
      breeding pairs were formed. Lesser kestrel males performed a large number of
      short foraging trips while females made a few long ones. This maximized the
      provisioning rate by males to feed their mates and offspring. Meanwhile, lesser
      kestrel females spent more time at the colony than males in order to defend the
      nest, incubate the eggs and brood the nestlings. Females also helped their mates
      to provision the nestling once these had grown and required more food and less
      protection. Furthermore, lesser kestrels showed a sexual spatial segregation in
      foraging areas, with males foraging closer to the colony than females.
      CONCLUSIONS: The lesser kestrel responds to changes in energy demand throughout
      the breeding season with its foraging movement strategy, but in a different way
      depending on parental sex. The sexual spatial segregation observed is likely to
      be the result of an adaptive foraging strategy based on role specialization to
      reduce prey depletion close to the colony and intersexual competition in order to
      improve breeding success.

PMID- 28451435
TI  - Circumcision in hemophilia using low quantity of factor concentrates: experience
      from Dakar, Senegal.
AB  - BACKGROUND: Circumcision in hemophiliacs is a delicate surgery because of
      bleeding risks that could be avoided by adequate substitution of coagulation
      factor. This practice is very challenging in countries where anti hemophilic
      treatment is inaccessible. The study aimed to evaluate a circumcision protocol in
      hemophilia A using low quantities of factor concentrates. METHODS: This
      prospective study included 26 hemophiliacs A who underwent circumcision in 2014.
      Medical treatment protocol using low quantity of factor concentrates was drafted
      by physicians of the Hemophilia Treatment Center and the surgical protocol by
      experienced surgeons. Assessment criteria were: number of hospitalization days,
      number of exposure days to factor concentrates, delay to healing and occurrence
      of bleeding events. RESULTS: Mean age was 9.6 years (1-30). Hemophiliacs patients
      were classified as severe (n = 8), moderate (n = 9) and mild form (n = 9). Mean
      number of exposure days to factor VIII concentrates was 6.9 days (5-12) in
      children and 10.75 days (7-16) in adults (p = 0.0049); mean number of
      hospitalization days was 3.68 days (2-10) in children and 13.5 days (13-15) in
      adults (p = 0.0000); delay to healing was 26.47 days (20-35) in children and
      25.25 days (22-30) in adults (p = 0.697); five haemophiliacs (19.2%) presented
      bleeding events after the circumcision. The mean amount of FIII concentrates used
      per patient was 1743 IU (810-2340). CONCLUSION: The study shows treatment
      protocol using low quantity of factor concentrates is efficient in hemophilia
      patients who underwent circumcision.

PMID- 28451436
TI  - Loading conditions in the spine, hip and knee during different executions of back
      extension exercises.
AB  - BACKGROUND: Back extension (BE) is a strength exercise for training the dorsal
      trunk and hip muscles. To optimise training recommendations that avoid
      overloading and possible injury, the aim of this study was to determine the
      loading conditions and the influence of different execution forms of BE on spine,
      hip and knee ranges of motion (RoMs), joint moments and muscle activity. METHODS:
      The kinematics, kinetics and muscle activity (EMG) of two execution types (BEh:
      dynamic hip, BEs: dynamic spine) and two versions (one-legged and two-legged) of
      BE were measured in 16 subjects. RoMs and external joint moments were calculated
      using an inverse dynamics approach and analysed with a linear mixed model.
      RESULTS: Although lumbar spine flexion was observed in both execution types,
      thoracic spine flexion predominantly occurred during BEs, whereas thoracic spine
      extension was observed during BEh. Larger maximal back and hip moments were
      observed for BEh than for BEs. The activity of the dorsal back and hip muscles,
      as observed using EMG, was increased for one-legged executions. CONCLUSION: To
      strengthen the hips and lower back, BEh seem to be more efficient due to the
      higher moments, with higher or similar RoMs in the hip and lower back. One-legged
      BEs seem to provide an effective training for the hamstrings and hip regions
      without subjecting the spine to excessive loading, possibly promoting this as an
      effective exercise during training and rehabilitation.

PMID- 28451437
TI  - An assessment of agricultural pesticide use in Iran, 2012-2014.
AB  - BACKGROUND: This is the first published assessment on agricultural pesticide use
      in Iran with the aim to identify pesticide products with a potential of causing
      acute or chronic hazard to human health. It also establishes a baseline for
      future comparisons and for trend assessments. METHODS: The amounts of imported
      technical materials for formulation by local manufacturers as well as imported
      final product formulations were extracted from the registration data of the Plant
      Protection Organization of Iran in 2012-2014. The hazard indicators used were
      acute oral toxicity and chronic toxicity. For the latter, carcinogenicity,
      mutagenicity, and adverse effects on reproduction or development (CMR toxicity),
      and low Acceptable Daily Intake (ADI) were used. The comparative potential of the
      active ingredients of concern in terms of chronic toxicity was assessed using the
      average annual volume of their estimated use divided by their respective ADI,
      called chronic hazard potential (CHP) in the present text. The contribution of
      individual pesticides in different use categories to the total CHP of the user
      category, was also calculated, using the average annual volume of the active
      ingredients of all pesticides used during the period 2012-2014. RESULTS: On
      average about 14,000 tonnes of agriculture pesticides, expressed in active
      ingredients (AI), were annually used in Iran. Herbicides constituted the largest
      volume (43%), followed by insecticides and acaricides (37%) and fungicides (19%).
      0.1% and 47% of the formulated products met the criteria of WHO Class Ib (highly
      hazardous) and Class II (moderately hazardous) products respectively. Aluminium
      phosphide and magnesium phosphide were identified as products of primary concern
      and chlorpyrifos, diazinon and paraquat as products of secondary concern, in
      terms of their acute human health hazard. No compound in carcinogenicity category
      1A or 1B or germ cell mutagenicity/reproduction toxicity category 1A was
      identified. Six compounds (diazinon, chlorpyrifos, dichlorvos, metam sodium,
      paraquat and dimethoate) were identified as products with chronic hazard
      potential based on a low ADI. CONCLUSIONS: The assessment identified and
      prioritized agriculture pesticide used in Iran in terms of their acute and
      chronic hazard to human health for re-registration scheme recently established by
      PPO and for risk mitigation. It also set priority for research into development
      of alternative products and practices to minimize pesticide risks. Chronic hazard
      potential - amount of use adjusted with toxicity may serve as a useful point of
      reference for trend analysis also in the use of less hazardous agricultural
      pesticide products.

PMID- 28451438
TI  - Genotyping-by-sequencing of pear (Pyrus spp.) accessions unravels novel patterns
      of genetic diversity and selection footprints.
AB  - Understanding of genetic diversity and marker-trait relationships in pears (Pyrus
      spp.) forms an important part of gene conservation and cultivar breeding.
      Accessions of Asian and European pear species, and interspecific hybrids were
      planted in a common garden experiment. Genotyping-by-sequencing (GBS) was used to
      genotype 214 accessions, which were also phenotyped for fruit quality traits. A
      combination of selection scans and association analyses were used to identify
      signatures of selection. Patterns of genetic diversity, population structure and
      introgression were also investigated. About 15 000 high-quality SNP markers were
      identified from the GBS data, of which 25% and 11% harboured private alleles for
      European and Asian species, respectively. Bayesian clustering analysis suggested
      negligible gene flow, resulting in highly significant population differentiation
      (Fst=0.45) between Asian and European pears. Interspecific hybrids displayed an
      average of 55% and 45% introgression from their Asian and European ancestors,
      respectively. Phenotypic (firmness, acidity, shape and so on) variation between
      accessions was significantly associated with genetic differentiation. Allele
      frequencies at large-effect SNP loci were significantly different between genetic
      groups, suggesting footprints of directional selection. Selection scan analyses
      identified over 20 outlier SNP loci with substantial statistical support, likely
      to be subject to directional selection or closely linked to loci under selection.

PMID- 28451441
TI  - Performance evaluation of the compounding robot, APOTECAchemo, for injectable
      anticancer drugs in a Japanese hospital.
AB  - BACKGROUND: The accuracy, safety and feasibility of, the compounding robot
      APOTECAchemo were evaluated in the clinical practice of Japan. METHODS: Accuracy
      and precision of robotic preparations by APOTECAchemo was evaluated in 20
      preparations of fluorouracil (FU) and cyclophosphamide (CPA) infusions by four
      pharmacists. Environmental and product contaminations with FU and CPA were
      evaluated by wipe testing. Robotic performance was compared with manual
      preparation in a biological safety cabinet. The number of robotic products, total
      compounding time and total pre-reconstitution time of lyophilized drugs between
      January 1, 2014 to December 31, 2015 were investigated. RESULTS: Robotic
      preparation resulted more accurate and precise (mean absolute dose error and
      coefficient of variation were 0.83 and 1.04% for FU and 0.52 and 0.59% for CPA)
      than those of manual preparation (respective values were 1.20 and 1.46% for FU
      and 1.70 and 2.20% for CPA). Drug residue was not detected from any of the
      prepared infusion bags with the robotic preparation, whereas FU was detected in
      two of four analyzed infusion bags with manual preparation. Average total time to
      make single anticancer drug preparation (compounding plus reconstitution of
      lyophilized drugs) was 6.11 min in the second half of 2015. During the study
      period, the highest percentage of production covered by APOTECAchemo was 70.4% of
      the total inpatient pharmacy activity. CONCLUSION: Robotic preparation using
      APOTECAchemo should give substantial advantages in drug compounding for accuracy
      and safety and was able to be successfully worked in Mie university hospital.

PMID- 28451439
TI  - The association of self-regulation with weight loss maintenance after an
      intensive combined lifestyle intervention for children and adolescents with
      severe obesity.
AB  - BACKGROUND: Knowledge is limited on the role the ability to self-regulate plays
      in the long-term outcome of obesity treatment in children and adolescents with
      severe obesity. The purpose of this study was to determine whether the ability to
      self-regulate after an one year intensive, partly inpatient, combined lifestyle
      intervention is associated with weight loss maintenance in children and
      adolescents with severe obesity. METHODS: One hundred twenty participants (8-19
      years) with an average SDS-BMI of 3.41 and their parents/caregivers were included
      in an intervention study. As primary determinant of weight loss maintenance,
      general self-regulation ability was evaluated using two behavioral computer tasks
      assessing inhibitory control and sensitivity to reward. RESULTS: There was no
      association between inhibitory control at T12 and ?SDS-BMI between T12 and T24
      (beta = 0.0002; CI 95% = -0.0010-0.0014; P = 0.761). There was also no relation
      between sensitivity to reward at T12 and ?SDS-BMI between T12 and T24 (beta = 
      0.0028; CI 95% = -0.0075-0.0019; P = 0.244). None of the psychosocial factors
      that were examined as moderators, showed a statistically significant interaction,
      except for parental feeding style (P = 0.023). CONCLUSIONS: The ability to self
      regulate after an intensive, partly inpatient, multidisciplinary one year
      intervention for severe obesity in children and adolescents was not associated
      with the ability to maintain the achieved weight loss during the following year.
      Factors that explain the large range of long term outcomes need to be elucidated.
      TRIAL REGISTRATION: Netherlands Trial Register (NTR1678, registered 20-Feb-2009).

PMID- 28451440
TI  - Microbiological screenings for infection control in unaccompanied minor refugees:
      the German Armed Forces Medical Service's experience.
AB  - BACKGROUND: The German Military Medical Service contributed to the medical
      screening of unaccompanied minor refugees (UMRs) coming to Germany in 2014 and
      2015. In this study, a broad range of diagnostic procedures was applied to
      identify microorganisms with clinical or public health significance. Previously,
      those tests had only been used to screen soldiers returning from tropical
      deployments. This instance is the first time the approach has been studied in a
      humanitarian context. METHODS: The offered screenings included blood cell counts,
      hepatitis B serology and microscopy of the stool to look for protozoa and worm
      eggs as well as PCR from stool samples targeting pathogenic bacteria, protozoa
      and helminths. If individuals refused certain assessments, their decision to do
      so was accepted. A total of 219 apparently healthy male UMRs coming from
      Afghanistan, Egypt, Somalia, Eritrea, Syria, Ghana, Guinea, Iran, Algeria, Iraq,
      Benin, Gambia, Libya, Morocco, Pakistan, and Palestine were assessed. All UMRs
      who were examined at the study department were included in the assessment.
      RESULTS: We detected decreasing frequencies of pathogens that included diarrhoea
      associated bacteria [Campylobacter (C.) jejuni, enteropathogenic Escherichia (E.)
      coli (EPEC), enterotoxic E. coli (ETEC), enteroaggregative E. coli (EAEC),
      enteroinvasive E. coli (EIEC)/Shigella spp.), Giardia (G.) duodenalis, helminths
      (comprising Schistosoma spp., Hymenolepis (H.) nana, Strongyloides (S.)
      stercoralis] as well as hepatitis B virus. Pathogenic microorganisms dominated
      the samples by far. While G. duodenalis was detected in 11.4% of the assessed
      UMRs, the incidence of newly identified cases in the German population was 4.5
      cases per 100,000 inhabitants. CONCLUSIONS: We conclude that the applied in-house
      PCR screening systems, which have proven to be useful for screening military
      returnees from tropical deployments, can also be used for health assessment of
      immigrants from the respective sites. Apparently healthy UMRs may be enterically
      colonized with a broad variety of pathogenic and apathogenic microorganisms.
      Increased colonization rates, as shown for G. duodenalis, can pose a hygiene
      problem in centralized homes for asylum seekers.

PMID- 28451442
TI  - Injection versus Decompression for Carpal Tunnel Syndrome-Pilot trial (INDICATE
      P)-protocol for a randomised feasibility study.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the commonest peripheral nerve
      disorder in the UK, with over 52,996 carpal tunnel decompressions performed in
      2011. By 2030, this figure is estimated to double. Whilst evidence supports
      conservative measures for mild symptoms, and early surgery for severe symptoms,
      controversy remains over the most appropriate management for patients that
      present with moderate disease, with regard to early surgery or late surgery
      following steroid injection. Injection versus Decompression for Carpal Tunnel
      Syndrome-Pilot trial (INDICATE-P) is a feasibility study for a multicentre,
      randomised controlled trial (INDICATE) to determine whether patients over the age
      of 18 with moderate CTS should undergo early surgical decompression of the median
      nerve or a single steroid injection (followed by later surgery if required).
      METHODS/DESIGN: INDICATE-P is a feasibility study for an open (non-blinded)
      randomised controlled pilot trial. Eligible participants will be adults with a
      clinical diagnosis of moderate CTS. This is defined as symptoms disturbing sleep
      or restricting activities of daily living or work, despite a 2-week trial of
      night splints. Participants will be randomised to one of two possible
      interventions: surgical decompression or a single steroid injection (followed by
      surgery later if required). Clinical outcome measures will be captured by postal
      questionnaire at 1, 3, 6 and 12 months post-randomisation. In order to improve
      the study design for the main INDICATE trial, feasibility data will also be
      collected to identify difficulties in recruitment and retention, to gain patient
      feedback on questionnaires and to confirm the suitability of the proposed outcome
      measures. DISCUSSION: The INDICATE-P feasibility study will contribute to the
      design and execution of the INDICATE trial, which will seek to assess the safety
      and effectiveness of two approaches to treatment for patients over 18 years of
      age with moderate CTS: early carpal tunnel decompression or a single steroid
      injection (followed by later surgery).

PMID- 28451443
TI  - Palliative care in heart failure: facts and numbers.
AB  - Millions of people worldwide have heart failure. Despite enormous advances in
      care that have improved outcome, heart failure remains associated with a poor
      prognosis. Worldwide, there is poor short-term and long-term survival. The 1 year
      survival following a heart failure admission is in the range of 20-40% with
      between-country variation. For those living with heart failure, the symptom
      burden is high. Studies report that 55 to 95% of patients experience shortness of
      breath and 63 to 93% experience tiredness. These symptoms are associated with a
      high level of distress (43-89%). Fewer patients experience symptoms such as
      constipation (25-30%) or dry mouth (35-74%). However, when they do, such symptoms
      are associated with high levels of distress (constipation: 15-39%; dry mouth: 14
      33%). Psychological symptoms also predominate with possibly as many as 50%
      experiencing depression. Palliative care services in heart failure are not widely
      available. Even in countries with well-developed services, only around 4% of
      patients are referred for specialist palliative care. Many patients and their
      families would benefit from receiving specialist palliative care support.

PMID- 28451445
TI  - Who are patients classified within the new terminology of heart failure from the
      2016 ESC guidelines?
AB  - AIMS: The main terminology used to describe heart failure (HF) is based on
      measurement of the left ventricular ejection fraction (LVEF). LVEF in the range
      of 40-49% was recently defined as HF with mid-range EF (HFmrEF) by the 2016
      European Society of Cardiology guidelines. The purpose of our study was to assess
      the clinical profile and prognosis of patients with HF according to this new
      classification. METHODS AND RESULTS: A total of 482 patients referred for HF were
      retrospectively included over a period of 1 year. There were 258 (53%), 115
      (24%), and 109 (23%) patients with HF with reduced EF (HFrEF), HFmrEF, and HF
      with preserved EF (HFpEF), respectively. Patient age increased, whereas left
      block bundle branch, brain natriuretic peptide level, and the use of beta-blocker
      and furosemide decreased from HFrEF to HFpEF. After adjustment for the age,
      patients with HFpEF and HFmrEF were more likely to have NYHA stage 2 dyspnea, had
      a higher systolic blood pressure, were less likely to have spironolactone, had
      lower furosemide dose, and had lower haemoglobin than those with HFrEF.
      Cardiovascular risk factors and medical history were similar in the three groups
      of patients. There was a 33% death rate after a mean follow-up of 32.2 +/- 14.3
      months. The survival was the same among patients whatever the group of HF (P =
      0.884). CONCLUSIONS: Patients with HFrEF, HFmrEF, and HFpEF share the same
      cardiovascular risk factors, medical history, and prognosis. Patients with HFmrEF
      have a different clinical profile, which is nearly the same as patients with
      HFpEF, except for sex. These results question the relevance of this new
      classification of HF to stimulate research into this new group of patients.

PMID- 28451444
TI  - Shared biomarkers between female diastolic heart failure and pre-eclampsia: a
      systematic review and meta-analysis.
AB  - Evidence accumulates for associations between hypertensive pregnancy disorders
      and increased cardiovascular risk later. The main goal of this study was to
      explore shared biomarkers representing common pathogenic pathways between heart
      failure with preserved ejection fraction (HFpEF) and pre-eclampsia where these
      biomarkers might be potentially eligible for cardiovascular risk stratification
      in women after hypertensive pregnancy disorders. We sought for blood markers in
      women with diastolic dysfunction in a first literature search, and through a
      second search, we investigated whether these same biochemical markers were
      present in pre-eclampsia.This systematic review and meta-analysis presents two
      subsequent systematic searches in PubMed and EMBASE. Search I yielded 3014
      studies on biomarkers discriminating women with HFpEF from female controls, of
      which 13 studies on 11 biochemical markers were included. Cases had HFpEF, and
      controls had no heart failure. The second search was for studies discriminating
      women with pre-eclampsia from women with non-hypertensive pregnancies with at
      least one of the biomarkers found in Search I. Search II yielded 1869 studies, of
      which 51 studies on seven biomarkers were included in meta-analyses and 79
      studies on 12 biomarkers in systematic review.Eleven biological markers
      differentiated women with diastolic dysfunction from controls, of which the
      following 10 markers differentiated women with pre-eclampsia from controls as
      well: C-reactive protein, HDL, insulin, fatty acid-binding protein 4, brain
      natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin,
      mid-region pro adrenomedullin, cardiac troponin I, and cancer antigen 125.Our
      study supports the hypothesis that HFpEF in women shares a common pathogenic
      background with pre-eclampsia. The biomarkers representing inflammatory state,
      disturbances in myocardial function/structure, and unfavourable lipid metabolism
      may possibly be eligible for future prognostic tools.

PMID- 28451446
TI  - Stem cell registry programme for patients with ischemic cardiomyopathy undergoing
      coronary artery bypass grafting: what benefits does it derive?
AB  - AIMS: Standardization of stem cell therapy requires application of appropriate
      methods to evaluate safety and efficacy, including long-term pharmacovigilance.
      To accomplish this objective, a long-term registry programme was installed.
      METHODS AND RESULTS: We analysed 150 patients with ischemic cardiomyopathy, who
      received intramyocardial CD133+ bone marrow mononuclear stem cell treatment
      combined with coronary artery bypass grafting (CABG) or CABG alone. The mortality
      rate, major adverse cerebral and cardiac events, and functional outcome
      parameters were evaluated for the time period up to 14 years follow-up. As a
      result, we have stratified the patient population (96 patients) into responders
      and non-responders. Furthermore, the analysis of relevant predictors of good
      response to CD133+ bone marrow mononuclear stem cell treatment was performed.
      Several positive tendencies related to stem cells transplantation were
      demonstrated. First, no significant difference in major adverse cardiovascular
      and cerebral events was observed between stem cell and control group up to 14
      years follow-up. Second, an improvement of left ventricle ejection fraction
      (LVEF) in stem cell group retained for 5 years in contrast with CABG-only group,
      where no significant changes in LVEF after 2 years were observed. In addition,
      LVEF under 30% and left ventricle end diastolic diameter above 60 mm were
      independent predictors of functional response to CD133+ cell therapy.
      CONCLUSIONS: Participants with overt heart failure benefit most from CABG
      combined with intramyocardial injection of CD133+ bone marrow mononuclear cell
      within the group. An improvement LVEF in stem cell group remained for 5 years in
      contrast with the CABG-only group. The patients, in whom the improvement of both
      LVEF and LVED was observed, have benefited by increased life expectancy.

PMID- 28451447
TI  - Dynamic changes of serum microRNA-122-5p through therapeutic courses indicates
      amelioration of acute liver injury accompanied by acute cardiac decompensation.
AB  - AIMS: Recent studies have shown that serum microRNA (miR) abundance is
      informative for the diagnosis or prognosis of heart failure. However, the
      dynamics and kinetics of miRs in acute heart failure are largely unknown. Serial
      measurement and analysis of serum miRs changes in individuals along their
      therapeutic course could reduce inter-individual variation and should detect
      potentially important serum miRs related to disease mechanisms. Based on this
      concept, we profiled serum miR signatures of blood samples that were obtained
      sequentially on the day of admission and on hospital Day 7. METHODS AND RESULTS:
      This prospective, observational study included 42 consecutive acute heart failure
      patients (74 +/- 1 years old, 24 male). From admission to Day 7, most of the
      patients showed clinical improvement. In such a cohort, we detected several
      fluctuations of serum miRs by two distinct screening methods (quantitative PCR
      and high-throughput sequencing). One of these fluctuating serum miRs, miR-122-5p,
      decreased significantly from Day 1 to Day 7 [median arbitrary unit (1st:3rd
      quantile value); 4.62 [2.39:12.3] to 3.07 [1.67:5.39], P = 0.007]. This
      fluctuation was significantly correlated with changes in serum liver function
      markers (estimated coefficient and 95% confidence interval; vs change in
      aspartate aminotransferase 1.69, 0.890-2.484, P < 0.001 and r = 0.560, vs change
      in alanine aminotransferase 1.09, 0.406-1.771, P = 0.007 and r = 0.428).
      CONCLUSIONS: The serum miR signature of patients with acute heart failure might
      indicate the severity of the disease or patients' response to therapeutic
      intervention. Notably, serum miR-122-5p levels reflect liver damage in this
      condition.

PMID- 28451448
TI  - Quality of life and long-term mortality in patients with advanced chronic heart
      failure treated with intermittent low-dose intravenous inotropes in an outpatient
      setting.
AB  - AIMS: There are limited data on the effect of low-dose, intermittent inotropic
      therapy in an outpatient setting on the quality of life (QOL) in patients with
      advanced refractory heart failure (HF) symptoms. We aimed to analyse the effect
      of this treatment modality on QOL and subsequent survival. METHODS AND RESULTS:
      The study population comprised 287 consecutive patients with advanced refractory
      HF symptoms who were treated with low-dose, intravenous intermittent inotropic
      therapy in the HF Day Care Service at Sheba Medical Centre between September 2000
      and September 2012. All patients completed a baseline Minnesota Living with Heart
      Failure Questionnaire (MLWHFQ), and 137 (48%) completed a 1 year follow-up
      questionnaire. MLWHFQ scores' means ranged from 0 (better QOL) to 5 (worse QOL).
      Mean age was 68 +/- 12, 86% were men, 77% had ischaemic cardiomyopathy, and the
      mean left ventricle ejection fraction (LVEF) was 26% +/- 13. The mean baseline
      MLWHFQ score was 3.1 (+/-1), while the mean at 1 year of treatment was of 2.7 (+/
      1.1), indicating an overall improvement in QOL associated with intermittent low
      dose inotrope therapy (p < 0.01). Multivariate analysis showed that younger age,
      non-ischaemic cardiomyopathy, and worse renal function were independently
      associated with improvement in QOL at 1 year. Improvement in QOL was not
      associated with a significant survival benefit during subsequent follow-up.
      CONCLUSIONS: In patients with advanced refractory HF symptoms, treatment with low
      dose, intermittent intravenous inotropes in an outpatient setting is associated
      with significant improvement in QOL. However, improvement in QOL in this
      population does not appear to affect subsequent long-term survival.

PMID- 28451449
TI  - Benefit of tolvaptan in the management of hyponatraemia in patients with diuretic
      refractory congestive heart failure: the SEMI-SEC project.
AB  - AIMS: Hyponatraemia is an electrolyte disorder that occurs in advanced congestive
      heart failure (HF) and worsens prognosis. We explored the usefulness of
      tolvaptan, which has shown promising results in the treatment of this condition.
      METHODS AND RESULTS: This study is based on a retrospective national registry
      (2011-15) of patients hospitalized with refractory HF and hyponatraemia who
      agreed to receive tolvaptan when standard treatment was ineffective. The benefit
      of tolvaptan was analysed according to the following criteria: normalization
      ([Na+] >= 135 mmol/L) or increased sodium levels [Na+] >= 4 mEq/L on completion
      of treatment, and increase in urine output by 300 or 500 mL at 48 h. Factors
      associated with tolvaptan benefit were explored. A total of 241 patients were
      included, 53.9% of whom had ejection fraction <40%. All patients received
      concomitant loop diuretics. Initial tolvaptan dose was 17.2 +/- 6.1 mg, and end
      dose was 26.4 +/- 23.2 mg (duration 7.8 +/- 8.6 days). Serum sodium
      concentrations increased significantly at 24-48 h, from 126.5 +/- 6.2 mEq/L at
      baseline to 134.1 +/- 6.1 mEq/L at the end of treatment (P < 0.0001). Weight fell
      by ~5 kg before discharge (P < 0.0001) and urine output increased 1.3-fold (P <
      0.0001). Normal sodium levels and/or increases of 500 mL in urine output were
      achieved by 90.8% of patients (35.7% achieved both) and 94.8% increased to [Na+]
      >= 4 mEq/L and/or +300 mL in urine output (54.4% both). CONCLUSIONS: An increase
      in sodium levels and/or improvement in urine output was observed in patients
      admitted for HF and refractory hyponatraemia under tolvaptan treatment. Tolvaptan
      may be useful in this setting, in which no effective proven alternatives are
      available.

PMID- 28451450
TI  - Serum albumin level and hospital mortality in acute non-ischemic heart failure.
AB  - AIMS: Hypoalbuminemia is common in heart failure (HF), especially in elderly
      patients. It is associated with an increased risk of death. The present study
      sought to examine the prognostic significance of serum albumin level in the
      prediction of hospital mortality in patients admitted for acute non-ischemic HF.
      METHODS AND RESULTS: We examined the association between albumin and hospital
      mortality in a cohort of 546 patients admitted for acute non-ischemic HF. None of
      the patients had infectious disease, severe arrhythmias (atrial fibrillation,
      ventricular tachycardia, ventricular fibrillation), required invasive
      ventilation, or presented with acute coronary syndrome or primary valvular
      disease. Thirty-six patients (7%) died during the hospital stay. These patients
      were significantly older (78 +/- 9 vs. 72 +/- 12 years; P = 0.006), had higher
      heart rate (P < 0.0001), increased creatinine level (P = 0.01), lower systolic
      and diastolic blood pressures (P < 0.05), elevated leucocyte count (P = 0.001),
      and lower albumin levels (31.3 +/- 5.6 g/L vs. 36.9 +/- 4.1 g/L; P < 0.001). With
      multivariable analysis, age (P = 0.01), heart rate (P < 0.0003), diastolic blood
      pressure (P < 0.01), leukocyte count (P = 0.009), and serum albumin level (P <
      0.0001) emerged as independent predictors of hospital mortality. Hypoalbuminemia
      (<34 g/L) yielded the best sensitivity (78.8%) and specificity (75%) for
      predicting hospital death. CONCLUSIONS: Serum albumin level measured at admission
      can serve as a simple prognostic factor in acute non-ischemic HF. Hypoalbuminemia
      is associated with increased risk of hospital mortality, especially in elderly
      patients.

PMID- 28451451
TI  - Abnormal haemodynamic postural response in patients with chronic heart failure.
AB  - AIM: The objective was to evaluate in treated heart failure (HF) patients whether
      multidrug therapy interferes with the cardiovascular autonomic response to
      postural stress. METHODS AND RESULTS: Blood pressure (BP; Finapres), heart rate
      (HR), stroke volume, and total peripheral resistance (TPR) responses to standing
      up were measured in 33 HF patients and 10 healthy age-matched controls. Ten
      hypertensive (HT) patients treated with a similar combination of drugs but
      without heart failure served as reference subjects to account for use of
      medication. Frequency domain measures of HR and BP variability were calculated as
      correlates of cardiovascular autonomic function. Postural hypotension was found
      in 16 out of 33 HF patients independently from New York Heart Association
      functional class. In HF patients vs. HT patients and healthy controls the
      haemodynamic postural response was abnormal with a large initial BP fall and a
      slackened reflex increase in TPR resulting in inadequate BP recovery. HR and BP
      variability were normal in HT patients and healthy controls but attenuated in HF
      patients. The magnitude of the postural HR, stroke volume, and TPR responses as
      well as HR and BP variability was inversely related to the New York Heart
      Association class. CONCLUSIONS: In HF patients, the autonomic vasomotor response
      to postural stress is abnormal, more pronounced with increasing disease severity,
      and frequently associated with overt postural hypotension. These phenomena appear
      related to the cardiac condition rather than treatment.

PMID- 28451452
TI  - Uric acid predicts mortality and ischaemic stroke in subjects with diastolic
      dysfunction: the Tromso Study 1994-2013.
AB  - AIMS: To investigate whether serum uric acid predicts adverse outcomes in persons
      with indices of diastolic dysfunction in a general population. METHODS AND
      RESULTS: We performed a prospective cohort study among 1460 women and 1480 men
      from 1994 to 2013. Endpoints were all-cause mortality, incident myocardial
      infarction, and incident ischaemic stroke. We stratified the analyses by
      echocardiographic markers of diastolic dysfunction, and uric acid was the
      independent variable of interest. Hazard ratios (HR) were estimated per 59
      MUmol/L increase in baseline uric acid. Multivariable adjusted Cox proportional
      hazards models showed that uric acid predicted all-cause mortality in subjects
      with E/A ratio <0.75 (HR 1.12, 95% confidence interval [CI] 1.00-1.25) or E/A
      ratio >1.5 (HR 1.51, 95% CI 1.09-2.09, P for interaction between E/A ratio
      category and uric acid = 0.02). Elevated uric acid increased mortality risk in
      persons with E-wave deceleration time <140 ms or >220 ms (HR 1.46, 95% CI 1.01
      2.12 and HR 1.13, 95% CI 1.02-1.26, respectively; P for interaction = 0.04).
      Furthermore, in participants with isovolumetric relaxation time <=60 ms,
      mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02-12.26,
      P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic
      stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03-2.53,
      P for interaction = 0.047). CONCLUSIONS: Increased uric acid was associated with
      higher all-cause mortality risk in subjects with echocardiographic indices of
      diastolic dysfunction, and with higher ischaemic stroke risk in persons with
      severely enlarged left atria.

PMID- 28451453
TI  - On admission serum sodium and uric acid levels predict 30 day rehospitalization
      or death in patients with acute decompensated heart failure.
AB  - AIMS: A considerable proportion of hospitalized patients for acute decompensated
      heart failure will be readmitted or die in short-term follow-up. In the present
      study, we aimed to assess the role of admission sodium (Na) and uric acid (UA)
      levels in the prediction of 30 day post-discharge heart failure readmission or
      all-cause mortality in advanced heart failure patients admitted with acute
      decompensation. METHODS AND RESULTS: One hundred and forty consecutive advanced
      heart failure patients who were admitted for a recent cardiac decompensation were
      enrolled in this prospective study. Serum Na and UA levels remained statistically
      unchanged during index admission (P = 0. 54 and 0.19, respectively). Within 30
      days post-discharge, composite end point of heart failure rehospitalization or
      all-cause death occurred in 62 (44.3%) patients (event group). Length of stay was
      statistically similar between patients in the event and non-event groups (P =
      0.38). No correlations were also found between length of stay and left
      ventricular ejection fraction, serum Na, UA, erythrocyte sedimentation rate
      (ESR), high-sensitivity C-reactive protein (hs-CRP), creatinine, and N-terminal
      pro b-type natriuretic peptide (NT-proBNP) levels (all P > 0.05). Lower left
      ventricular ejection fraction and Na and higher UA on admission were
      significantly associated with 30 day event both in univariate and multivariate
      analyses. CONCLUSIONS: Given the predictive role of baseline Na and UA for early
      post-discharge outcome and the absence of significant changes in their levels
      during initial hospitalization, admission Na and UA can be considered as
      prognosticators of acute decompensated heart failure, which their prognostic
      significance cannot be affected by routine acute heart failure therapy.

PMID- 28451454
TI  - Periodontitis and bone metabolism in patients with advanced heart failure and
      after heart transplantation.
AB  - AIMS: Heart failure (HF) is a multi-organ, pro-inflammatory syndrome that impairs
      bone metabolism. Pro-inflammatory cytokines and bone catabolism enhance
      periodontal disease, a local inflammatory, bacteria-induced disease that causes
      bone loss and periodontal soft tissue destruction. METHODS AND RESULTS: Medical
      and dental examinations were performed on patients with HF (n = 39), following
      heart transplantation (post-HTx, n = 38) and controls (n = 32). Blood, saliva,
      and gingival crevicular fluid were analysed for bone metabolism and inflammation
      markers. HF average New York Heart Association classification was III. Average
      time since HTx was 1414 days. Pro-inflammatory tumour necrosis factor-alpha was
      higher in HF and HTx as compared with controls (P < 0.05). Both HF and HTx
      participants had higher levels of bone resorption marker C-terminal telopeptide
      and parathyroid hormone with subjects in the HF group having the highest serum
      levels of all groups (P <= 0.05). In contrast, 25-hydroxyvitamin D was lowest in
      HF. HF patients had greater clinical attachment loss, cumulative pockets depth
      (greater than 3 mm) and probing depth (P < 0.05) as compared with controls.
      Cumulative pockets depth correlated significantly with measures of the
      inflammatory burden, beta-glucuronidase in saliva (r = 0.4863, P < 0.01),
      interleukin-1b in saliva (r = 0.5149, P < 0.01), and gingival crevicular fluid (r
      = 0.6056, P < 0.001) in HF. However, adjustment of periodontal results for
      measures of oral hygiene (plaque, bleeding on probing), systemic 25
      hydroxyvitamin D, and race attenuated significant differences between groups.
      CONCLUSIONS: Patients with HF exhibit more severe periodontal disease associated
      with increased bone turnover markers when compared with control patients.
      However, local and systemic factors may account for this association and should
      be evaluated in future studies.

PMID- 28451455
TI  - Metabolic profiles in heart failure due to non-ischemic cardiomyopathy at rest
      and under exercise.
AB  - AIMS: Identification of metabolic signatures in heart failure (HF) patients and
      evaluation of their diagnostic potential to discriminate HF patients from healthy
      controls during baseline and exercise conditions. METHODS: Plasma samples were
      collected from 22 male HF patients with non-ischemic idiopathic cardiomyopathy
      and left ventricular systolic dysfunction and 19 healthy controls before (t0), at
      peak (t1) and 1 h after (t2) symptom-limited cardiopulmonary exercise testing.
      Two hundred fifty-two metabolites were quantified by gas chromatography-mass
      spectrometry (GC-MS) and liquid chromatography (LC)-MS/MS-based metabolite
      profiling. RESULTS: Plasma metabolite profiles clearly differed between HF
      patients and controls at t0 (P < 0.05). The metabolic signature of HF was
      characterized by decreased levels of complex lipids and fatty acids, notably
      phosphatidylcholines, cholesterol, and sphingolipids. Moreover, reduced glutamine
      and increased glutamate plasma levels, significantly increased purine degradation
      products, as well as signs of impaired glucose metabolism were observed. The
      metabolic differences increased strongly according to New York Heart Association
      functional class and the addition of three metabolites further improved
      prediction of exercise capacity (Q2 = 0.24 to 0.35). Despite a high number of
      metabolites changing significantly with exercise (30.2% at t1/t0), the number of
      significant alterations between HF and controls was almost unchanged at t1 and t2
      (30.7 and 29.0% vs. 31.3% at t0) with a similar predictive group separation (Q2 =
      0.50 for t0, 0.52 for t1, and 0.56 for t2, respectively). CONCLUSIONS: Our study
      identified a metabolic signature of non-ischemic HF with prominent changes in
      complex lipids including phosphatidylcholines, cholesterol, and sphingolipids.
      The metabolic changes were already evident at rest and largely preserved under
      exercise.

PMID- 28451456
TI  - Immunosuppressive treatment in fulminant myocarditis and gene expression pattern
      associated with, but no histological confirmation of giant cell myocarditis.
AB  - A healthy woman with acute onset of pulmonary oedema and severely depressed left
      ventricular function underwent endomyocardial biopsy under the clinical suspicion
      of fulminant myocarditis. While awaiting the results of biopsy, the situation
      deteriorated to Interagency Registry for Mechanically Assisted Circulatory
      Support (INTERMACS) and extracorporeal membrane oxygenation was implanted.
      Finally, immunohistochemistry in biopsy specimen corresponded to fulminant
      lymphocytic myocarditis, although active myocarditis was excluded. Furthermore,
      gene expression profiling identified giant cell myocarditis although multinuclear
      cells were absent. This prompted the start of immunosuppression with cortisone
      and cyclosporine. The patient fully recovered.

PMID- 28451458
TI  - KRAS mutation in papillary fibroelastoma: a true cardiac neoplasm?
AB  - Primary cardiac tumours are rare and mostly benign lesions. Recent publications
      report that cardiac papillary fibroelastomas are the most common benign primary
      heart tumour, outnumbering myxomas. However, there is no consensus about their
      aetiology. We investigated the molecular profile of these tumours using next
      generation sequencing in a cohort of 16 cases. Eleven of 14 (79%) analysable
      tumours showed mutations of the KRAS oncogene. Our results provide unambiguous
      evidence that a significant proportion of these lesions are genuine neoplastic
      tumours caused by an oncogenic driver mutation.

PMID- 28451457
TI  - Fluorescence in situ hybridization in surgical pathology: principles and
      applications.
AB  - Identification of recurrent tumour-specific chromosomal translocations and novel
      fusion oncogenes has important diagnostic, therapeutic and prognostic
      implications. Over the past decade, fluorescence in situ hybridization (FISH)
      analysis of tumour samples has been one of the most rapidly growing areas in
      genomic medicine and surgical pathology practice. Unlike traditional
      cytogenetics, FISH affords a rapid analysis of formalin-fixed, paraffin-embedded
      cells within a routine pathology practice workflow. As more diagnostic and
      treatment decisions are based on results of FISH, demand for the technology will
      become more widespread. Common FISH-detected alterations are chromosome
      deletions, gains, translocations, amplifications and polysomy. These chromosome
      alterations may have diagnostic and therapeutic implications for many tumour
      types. Integrating genomic testing into cancer treatment decisions poses many
      technical challenges, but rapid progress is being made to overcome these
      challenges in precision medicine. FISH assessment of chromosomal changes relevant
      to differential diagnosis and cancer treatment decisions has become an important
      tool for the surgical pathologist. The aim of this review is to provide a
      theoretical and practical survey of FISH detected translocations with a focus on
      strategies for clinical application in surgical pathology practice.

PMID- 28451459
TI  - Chemokine (C-C motif) receptor 7 (CCR7) associates with the tumour immune
      microenvironment but not progression in invasive breast carcinoma.
AB  - Some previous studies have reported that the chemokine (C-C motif) receptor 7
      (CCR7) plays a role in breast cancer, is associated with lymph node metastasis
      and drives the site of distant metastasis. However, the impact of its expression
      on patient outcome and its association with tumour infiltrating inflammatory
      cells remain to be validated. We evaluated CCR7 protein expression by
      immunohistochemistry in a large well characterized cohort (n = 866) of early
      invasive primary breast cancers. CCR7 was expressed in the cytoplasm and membrane
      of tumour cells. We observed a weak positive association of high CCR7 expression
      when in either cellular component, but not both together, with axillary lymph
      node stage 3 tumours (p = 0.043). Logistic regression analysis of lymph node
      stage revealed no independent predictive value for CCR7 expression. CCR7
      expression was higher in HER2 positive tumours (p = 0.03) and associated with
      positive CD68+ FOXP3+ tumour infiltrating cells. CCR7 staining was negatively
      associated with CD3+ cells. There was no significant association of CCR7
      expression with breast cancer recurrence or survival. We conclude that while CCR7
      is not a useful biomarker for predicting lymph node metastasis, it may reflect
      altered intra- and inter-cellular signalling related to the immune
      microenvironment. The subcellular localization of CCR7 appears to affect the
      nature of these interactions.

PMID- 28451460
TI  - Next generation sequencing of the nidus of early (adenosquamous proliferation
      rich) radial sclerosing lesions of the breast reveals evidence for a neoplastic
      precursor lesion.
AB  - We sought to determine if adenosquamous proliferation of early cellular radial
      sclerosing lesions of the breast harbours hot spot mutations and to help clarify
      its relationship to low-grade adenosquamous carcinoma as a potential form of
      early neoplasia. Four low-grade adenosquamous carcinomas, early radial sclerosing
      lesions from 13 individuals, and 4 benign proliferative breast lesions were
      microdissected and assessed with a 50-gene Hot-spot cancer panel. Early radial
      sclerosing lesions were selectively microdissected concentrating on their
      adenosquamous proliferation (nidus). Hot spot mutations in PIK3CA were detected
      in ten (77% of) radial sclerosing lesions, in one low-grade adenosquamous
      carcinoma, and in usual ductal hyperplasia and apocrine adenosis. Over three
      quarters of individuals with cellular (adenosquamous proliferation rich) early
      radial sclerosing lesions tested harboured somatic mutations in PIK3CA suggesting
      that adenosquamous proliferation is a clonal lesion. Its relationship to low
      grade adenosquamous carcinoma remains unclear in view of the small sample size
      and unmatched radial sclerosing lesions and low-grade adenosquamous carcinomas.

PMID- 28451461
TI  - PLA2G7 associates with hormone receptor negativity in clinical breast cancer
      samples and regulates epithelial-mesenchymal transition in cultured breast cancer
      cells.
AB  - Breast cancer is the leading cause of cancer-related deaths in women due to
      distinct cancer subtypes associated with early recurrence and aggressive
      metastatic progression. High lipoprotein-associated phospholipase A2 (PLA2G7)
      expression has previously been associated with aggressive disease and metastasis
      in prostate cancer. Here, we explore the expression pattern and functional role
      of PLA2G7 in breast cancer. First, a bioinformatic analysis of genome-wide gene
      expression data from 970 breast samples was carried out to evaluate the
      expression pattern of PLA2G7 mRNA in breast cancer. Second, the expression
      profile of PLA2G7 was studied in 1042 breast cancer samples including 89 matched
      lymph node metastasis samples using immunohistochemistry. Third, the effect of
      PLA2G7 silencing on genome-wide gene expression profile was studied and validated
      in cultured breast cancer cells expressing PLA2G7 at high level. Last, the
      expression pattern of PLA2G7 mRNA was investigated in 24 nonmalignant tissue
      samples and 65 primary and 7 metastatic tumour samples derived from various
      organs using qRT-PCR. The results from clinical breast cancer samples indicated
      that PLA2G7 is overexpressed in a subset of breast cancer samples compared to its
      expression in benign breast tissue samples and that high PLA2G7 expression
      associated with hormone receptor negativity as well as with poor prognosis in a
      subset of breast cancer samples. In vitro functional studies highlighted the
      putative role of PLA2G7 in the regulation of epithelial-mesenchymal transition
      (EMT)-related signalling pathways, vimentin and E-cadherin protein expression as
      well as cell migration in cultured breast cancer cells. Furthermore, supporting
      the findings in breast and prostate cancer, high PLA2G7 mRNA expression was
      associated with metastatic cancer in four additional organs of origin. In
      conclusion, our results indicate that PLA2G7 is highly expressed in a subset of
      metastatic and aggressive breast cancers and in metastatic samples of various
      tissues of origin and promotes EMT and migration in cultured breast cancer cells.

PMID- 28451462
TI  - Pulmonary adenocarcinoma with mucin production modulates phenotype according to
      common genetic traits: a reappraisal of mucinous adenocarcinoma and colloid
      adenocarcinoma.
AB  - Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA)
      of the lung represent separate tumour entities, or simply lie within a spectrum
      of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK
      rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas
      (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by
      immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2,
      MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin),
      neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related
      (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial
      (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS)
      for 50 recurrently altered cancer genes. Unsupervised clustering analysis using
      molecular features identified cluster 1 (IMA and ICA), cluster 2 (ALKA and KRASA)
      and cluster 3 (MBA) (p < 0.0001). Cluster 1 showed four histology-independent sub
      clusters (S1 to S4) pooled by HFN4A and MUC5AC but diversely reacting for TTF1,
      MUC1, MUC2, MUC6 and CDX2. Sub-cluster S1 predominantly featured intestinal
      alveolar, S2 gastrointestinal, S3 gastric and S4 alveolar differentiation. In
      turn, KRASA and ALKA shared alveolar lineage alongside residual MUC5AC
      expression, with additional focal CDX2 and diffuse vimentin, respectively. A
      proximal-to-distal scheme extending from terminal (TB) and respiratory (RB)
      bronchioles to alveolar cells was devised, where S3 originated from distal TB
      (cellular mucinous adenocarcinoma), S2 from proximal RB (secreting mucinous
      adenocarcinoma), S1 from intermediate RB (mucin lake-forming colloid
      adenocarcinoma), S4 from distal RB (colloid alveolar adenocarcinoma), KRASA from
      juxta-alveolar RB (KRAS-mutated non-mucinous adenocarcinoma) and ALKA from juxta
      bronchial alveolar cells (ALK-translocated adenocarcinoma). TNGS analysis showed
      KRAS, LKB1, TP53, APC and CDKN2A mutation predominance. In conclusion, IMA and
      ICA are basket categories, which likely originate from distinct domains of
      stem/progenitor cells spatially distributed along bronchioles upon common
      molecular features and genetic alterations.

PMID- 28451463
TI  - Macular edema is a rare finding in untreated vitreoretinal lymphoma: small case
      series and review of the literature.
AB  - BACKGROUND: To determine the occurrence of macular edema (ME) in vitreoretinal
      lymphoma (VRL). METHODS: Retrospective analysis of 17 patients (31 eyes) with
      VRL. A review of the literature was done as well. RESULTS: Nine patients (15
      eyes) had fluorescein angiography and/or optical coherence tomography at
      presentation. In the ME group (six eyes of four patients), three patients (five
      eyes) had prior chemotherapy and radiation. Excluding eyes with radiation
      retinopathy (three eyes), rate of ME was 25% (3/12). When two unirradiated fellow
      eyes of eyes with radiation retinopathy were also excluded, ME rate was 10%
      (1/10). Excluding the eyes with intraocular surgery, the rate of ME was 0%. In
      the group without ME (nine eyes of six patients), one patient (one eye) was
      treated with chemotherapy and radiation and three patients (five eyes) with
      chemotherapy. Review of the literature showed that the ME was found between 2 and
      60% of cases, but most of the cases with ME had prior interventions. CONCLUSIONS:
      Macular edema in VRL is not uncommon but usually related to prior interventions.
      Macular edema as an initial presentation of VRL is rare.

PMID- 28451464
TI  - Activity-based assessment of an engineered hyperthermophilic protein as a capture
      agent in paper-based diagnostic tests.
AB  - Antibodies have traditionally served as the affinity reagents of choice in point
      of-care diagnostic biosensors. However, this class of proteins is not ideally
      suited for this use, being poorly characterized and prone to thermal
      denaturation. Here, we present an activity-based assessment of an alternative
      engineered binding protein in a cellulose-based assay.

PMID- 28451465
TI  - Intimate Partner Violence Victimization in LGBT Young Adults: Demographic
      Differences and Associations with Health Behaviors.
AB  - OBJECTIVE: Intimate partner violence (IPV) is an important public health problem
      with high prevalence and serious costs. Although literature has largely focused
      on IPV among heterosexuals, studies have recently begun examining IPV in LGBT
      samples, with mounting evidence suggesting IPV may be more common among LGBT
      individuals than heterosexuals. Less research has examined the specific health
      consequences of IPV in this population, particularly across time and among young
      people, and it remains unclear whether experiences of IPV differ between
      subgroups within the LGBT population (e.g. race, gender identity, and sexual
      orientation). METHOD: An ethnically diverse sample of 172 LGBT young adults
      completed self-report measures of IPV, sexual behavior, mental health, and
      substance abuse at two time points (4- and 5-year follow-up) of an ongoing
      longitudinal study of LGBT youth. RESULTS: IPV was experienced non-uniformly
      across demographic groups. Specifically, female, male-to-female transgender, and
      Black/African-American young adults were at higher risk compared to those who
      identified as male, female-to-male transgender, and other races. Being a victim
      of IPV was associated with concurrent sexual risk taking and prospective mental
      health outcomes but was not associated with substance abuse. CONCLUSIONS:
      Demographic differences in IPV found in heterosexuals were replicated in this
      LGBT sample, though additional research is needed to clarify why traditional risk
      factors found in heterosexual young people may not translate to LGBT individuals.
      Studies examining the impact of IPV on negative outcomes and revictimization over
      time may guide our understanding of the immediate and delayed consequences of IPV
      for LGBT young people.

PMID- 28451466
TI  - Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.
AB  - Progress in the development of assays for measuring cardiac action potential is
      crucial for the discovery of drugs for treating cardiac disease and assessing
      cardiotoxicity. Recently, high-throughput methods for assessing action potential
      using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two
      dimensional monolayer cultures and three-dimensional tissues have been developed.
      We describe an improved method for assessing cardiac action potential using an
      ultra-fast cost-effective plate reader with commercially available dyes. Our
      methods improve dramatically the detection of the fluorescence signal from these
      dyes and make way for the development of more high-throughput methods for cardiac
      drug discovery and cardiotoxicity.

PMID- 28451467
TI  - Skin Protectants Made of Curable Polymers: Effect of Application on Local Skin
      Temperature.
AB  - Objective: To measure the skin temperature after application of a new skin
      protectant intended for incontinence-associated dermatitis (IAD), compared with a
      commercial product with an analogous cyanoacrylate-based chemistry. Approach:
      Twelve healthy human volunteers received an application of the new product on one
      thigh and of the comparator on the other thigh. An infrared camera using
      ThermaCAMTM software imaged the skin and measured the temperature at the skin
      surface over time to characterize the thermal cure profile induced by the
      products on the skin. Results: The new product led to a drop in skin surface
      temperature (endothermic reaction), whereas the commercial product displayed an
      exotherm and a slight rise in skin surface temperature. Innovation: Cyanoacrylate
      based chemistries come in various formulations, differing in the side chains and
      additives used. They are liquid monomers that polymerize after application, and
      this polymerization is accompanied by an exothermic reaction that can be
      perceived as an unpleasant warming sensation, especially on compromised skin. A
      new formulation was designed to mitigate this rise in temperature. Conclusion:
      The new skin protectant may potentially be more comfortable for IAD patients,
      since it causes a drop in skin surface temperature instead of a rise during the
      curing process that follows application.

PMID- 28451468
TI  - A Feasibility Study of Intermittent Electrical Stimulation to Prevent Deep Tissue
      Injury in the Intensive Care Unit.
AB  - Objective: The primary goal of this study was to investigate the feasibility of
      utilizing intermittent electrical stimulation (IES) in an intensive care
      environment as a potential method for preventing pressure ulcers. Furthermore, we
      wished to evaluate the practicality of the innovation and end-user acceptability.
      Approach: Twenty immobile subjects, age ranging from 19 to 86 years old with a
      Braden Scale score ranging from 9 to 16 (very high to moderate risk of developing
      pressure ulcers), were enrolled. Intermittent 35 Hz electrical stimulation was
      administered through surface electrodes to the gluteal muscles causing them to
      contract for 10 s every 10 min. Subjects utilized IES on a program that increased
      from 4 to 24 h per day over 8 days and lasted up to a maximum of 4 weeks.
      Results: Bedside nurses reported that IES was simple to use, took an average of 6
      min to apply, and 2 min to remove. Furthermore, IES could be easily incorporated
      into routine patient care. No pressure ulcers occurred in any subject during the
      study. No untoward reactions or adverse events had occurred directly as a result
      of IES. Innovation: IES represents a potential method of preventing bedsores.
      This study represents a necessary pilot study, investigating safety and
      feasibility before proceeding with a larger randomized controlled trial to
      determine efficacy. Conclusion: Our results suggest that IES is both safe and
      feasible to implement in intensive care units.

PMID- 28451469
TI  - Comparative Effectiveness of Clostridial Collagenase Ointment to Medicinal Honey
      for Treatment of Pressure Ulcers.
AB  - Objective: Compare enzymatic debridement using clostridial collagenase ointment
      (CCO) with autolytic debridement using medicinal honey in the hospital outpatient
      setting for treating pressure ulcers (PUs). Approach: Retrospective deidentified
      electronic health records from 2007-2013 were extracted from the U.S. Wound
      Registry. Propensity score matching followed by multivariable analyses was used
      to adjust for selection bias and assess treatment effects comparing CCO-treated
      versus honey-treated PUs. Key outcomes included 100% granulation and
      epithelialization at 1 year. Results: Five hundred seventeen CCO-treated PUs (446
      patients) were matched to corresponding honey-treated PUs (341 patients). The
      majority of PUs were stage III (CCO 56%, honey 55%). CCO users had significantly
      fewer total visits (9.1 vs. 12.6; p < 0.001), fewer total selective sharp
      debridements (2.7 vs. 4.4; p < 0.001), and fewer PUs receiving negative pressure
      wound therapy (29% vs. 38%; p = 0.002) compared with honey. Innovation: CCO
      treated PUs were 38% more likely to achieve 100% granulation compared to honey
      treated PUs at 1 year, p = 0.018. Mean days to 100% granulation were
      significantly lower for CCO-treated PUs (255 vs. 282 days, p < 0.001). CCO
      treated PUs were 47% (p = 0.024) more likely to epithelialize at 1 year compared
      to PUs treated with honey. Mean days to epithelialization were significantly
      lower for PUs treated with CCO at 1 year (288 vs. 308 days; p = 0.011).
      Conclusion: All stages of PUs treated with CCO achieved faster rates of
      granulation and subsequent epithelialization compared to PUs treated with
      medicinal honey as measured by real-world data collected in the hospital
      outpatient department care setting.

PMID- 28451470
TI  - Autologous Bone Marrow Aspirate Therapy for Skin Tissue Engineering and Tissue
      Regeneration.
AB  - Introduction: Chronic wounds that are difficult to heal are physical and
      financial burden to the sufferer and a challenge to the treating physician.
      Objective: The main purpose of this study was to develop a novel method of using
      bone marrow (BM) aspirate, either cultured or fresh, as early solution for
      healing of chronic wounds and further reduce infection and tissue necrosis.
      Approach: In this case-control study conducted on 75 patients with chronic
      wounds, 50 patients with aspirate or cultured BM were used as cases and 25 with
      only daily saline dressings were used as controls. Results: Autologous BM
      aspirate either as fresh or cultured even without identification, isolation, and
      selective application of stem cells achieved significant reduction in the wound
      surface area when compared with control group. Innovation: The application of
      cultured BM cells had significantly higher percentage reduction of wound size
      compared to freshly applied BM aspirate; this reflects a high importance of stem
      cell therapy. Conclusion: The acceptability of the procedure among the patients
      was highly encouraging. The entire procedure was safe and without any
      complication.

PMID- 28451471
TI  - Can Handgrip Strength Improve Following Body Mass-Based Lower Body Exercise?
AB  - Knee extension strength (KES) improves following body mass-based lower body
      exercise training; however, it is unknown whether this type of exercise increases
      handgrip strength (HGS) as a result of a cross-education effect in older
      individuals. Our aim was to investigate the effect of a body mass-based exercise
      intervention on HGS and KES in older adults. At baseline, 166 subjects started a
      12-week intervention program, and 160 (108 women and 52 men) subjects completed
      the study. A self-selected group of 37 older adults (21 women and 16 men) served
      as a control group. HGS, KES, and ultrasound-derived anterior thigh muscle
      thickness (anterior thigh MT) were measured at baseline and post-testing, and
      relative strength of the knee extensor (KES/anterior thigh MT) was calculated. A
      linear regression model controlling for baseline values of body-mass index, %
      body fat, fat-free mass, HGS, chair stand time, anterior thigh MT, and KES/body
      mass ratio found a significant difference between control and training groups for
      KES post-testing values (p = 0.001) and anterior thigh MT post-testing values (p
      = 0.012), but not for HGS post-testing values (p = 0.287). Our results suggest
      that increases in lower body strength and muscle size following a 12-week lower
      body mass-based exercise intervention fail to translate into improvements in HGS.

PMID- 28451472
TI  - Cataract Surgery and Visual Acuity in Elderly Japanese: Results of Fujiwara-kyo
      Eye Study.
AB  - The aim of this study was to determine the presence of prior cataract surgery and
      best-corrected visual acuity (BCVA) in an elderly Japanese cohort. The Fujiwara
      kyo Eye Study was a prospective, population-based, cross-sectional
      epidemiological study. The subjects were >=68 years who lived in the Nara
      Prefecture and responded to recruitment notices. All of the subjects underwent
      comprehensive ophthalmological examinations, and the sociodemographic information
      and medical history, including prior cataract surgery, were obtained by answers
      to a questionnaire. The associations between the BCVA, age, sex, and history of
      cataract surgery were determined. A total of 2,873 subjects whose mean age was
      76.3 +/- 4.9 (mean +/- standard deviation) years were studied. The mean BCVA was 
      0.020 +/- 0.14 logarithm of the minimum angle of resolution units, and it was
      significantly better in the group with education >=13 years (p < 0.01). Overall,
      24.2% of the subjects had undergone cataract surgery, and 41.7% of the subjects
      >=80 years had undergone cataract surgery. The incidence of prior cataract
      surgery increased with increasing age (p < 0.001 for trend). The mean BCVA of
      eyes with cataract surgery was significantly better than that of eyes without
      cataract surgery in subjects >=80 years (p < 0.01). Visual acuity was generally
      good in this cohort of elderly Japanese subjects. In this cohort, 24.2% of the
      subjects had undergone cataract surgery, and the subjects >=80 years had better
      BCVA than those without cataract surgery.

PMID- 28451473
TI  - Blunted reward processing in remitted melancholic depression.
AB  - Blunted reward response appears to be a trait-like marker of vulnerability for
      Major Depressive Disorder (MDD). As such, it should be present in remitted
      individuals; however, depression is a heterogeneous syndrome. Reward-related
      impairments may be more pronounced in individuals with melancholic depression.
      The present study examined neural responses to rewards in remitted melancholic
      depression (rMD; N = 29), remitted non-melancholic depression (rNMD; N = 56), and
      healthy controls (HC; N = 81). Event-related potentials to monetary gain and loss
      were recorded during a simple gambling paradigm. rMD was characterized by a
      blunted response to rewards relative to both the HC and the rNMD groups, who did
      not differ from one another. Moreover, the rMD and rNMD groups did not differ in
      course or severity of their past illnesses, or current depressive symptoms or
      functioning. Results suggest that blunted response to rewards may be a viable
      vulnerability marker for melancholic depression.

PMID- 28451474
TI  - Adjuvant Radiotherapy for Thymic Neuroendocrine Tumors: A Case Report and Review
      of the Literature.
AB  - Thymic carcinoid tumors are very rare. Between two and four percent of carcinoids
      originate from the thymus with an estimated incidence of 1.5 to 3 per 10,000,000
      persons per year. Thymic carcinoids can be associated with the multiple endocrine
      neoplasia (MEN) type 1. The principal treatment is surgical resection. The
      potential roles of systemic and radiation treatments are a matter of debate. We
      describe the successful multidisciplinary treatment of a case of thymic carcinoid
      associated with MEN and review the literature pertaining to the use of adjuvant
      thoracic radiation.

PMID- 28451475
TI  - An Unusual Cause of Small Bowel Obstruction: A Case Report.
AB  - Small bowel obstruction is a common surgical emergency. The common causes are
      adhesions, malignancies, and hernias. We present a rare case of small intestinal
      obstruction caused by an enterolith in the distal ileum in a patient with an
      apparently normal gut.  A 59-year-old male who underwent gastrojejunostomy 15
      years back presented with features of intestinal obstruction of five days'
      duration. After initial conservative management, the patient was taken up for
      laparotomy. An enterolith causing obstruction was found in the distal ileum, and
      it was crushed and milked into the colon. The patient made an uneventful
      recovery.  The chyme crossing the ileum is usually liquid or semi-solid and hence
      luminal obstruction by the faecal bolus in the ileum is very unusual. In patients
      with previous gastric surgeries where the pylorus is bypassed, the solid food
      particles enter the small intestine and can form a bezoar. This patient was
      managed with laparotomy and milking of the stool bolus into the colon. Other
      treatment options include enterotomy or resection of the diseased bowel and
      removal of the enterolith.  Small bowel obstruction due to an enterolith is very
      rare and can pose a diagnostic challenge.

PMID- 28451476
TI  - Angiosarcoma of the Colon Presenting with Chronic Diarrhea, Rectal Bleeding, and
      Pelvic Discomfort.
AB  - Colonic angiosarcoma is a rare malignancy representing only 0.0012% of all
      colorectal malignancies. Due to its non-specific symptoms, diagnosis is often
      delayed. However, because of the aggressive nature of this malignancy, it is
      important to keep it in the differential diagnosis of rectal bleeding, pelvic
      discomfort, chronic diarrhea, and weight loss in patients with risk factors. We
      present a case of angiosarcoma of the colon in a 74-year-old female with a remote
      history of chemo-radiation for anal squamous cell carcinoma (ASCC).

PMID- 28451477
TI  - Knowledge and Attitude About Sexually Transmitted Infections Amongst Truck
      Drivers in Southern Punjab, Pakistan.
AB  - INTRODUCTION: There is very limited knowledge about sexually transmitted
      infections (STIs) transmission and prevention present amongst high-risk groups
      such as truck drivers in Pakistan because of lack of awareness and understanding
      about barrier techniques. OBJECTIVE: The aim of this study was to collect and
      access the data gathered from truck drivers about symptoms of STIs, their
      attitude towards hazards of multiple sexual partners, homosexuality, transmission
      and consequences of STIs, and their perception about preventing it using condoms
      and other barrier methods. METHODS: This study was conducted at small roadside
      tea stalls and local rest areas on Karachi road, Lodhran near the city of
      Bahawalpur in Southern Punjab, Pakistan. A structured questionnaire was designed,
      and 50 willing truck drivers of the city of Bahawalpur were included and
      interviewed. It was a cross-sectional study. Data was collected on knowledge
      about the STIs and use of barrier methods like condoms. Quantitative data was
      assessed and analyzed using SPSS version 23.0 (IBM, NY, USA). RESULTS: Fifty
      truck drivers of Bahawalpur were interviewed via standardized questionnaire in
      this study. All of them provided answers about their knowledge of STIs. Twenty
      drivers (40%) reported burning micturition, and only two (four percent) knew the
      real cause of it. Thirty-two (64%) of them were well aware of the use of condoms.
      Thirty-eight (76%) truck drivers had the knowledge about the adverse effects of
      multiple sex partners. CONCLUSION: The truck drivers of Bahawalpur city are quite
      vulnerable to STIs and this demonstrates the importance of prevention programs
      that can target this particular group. A significant number of the respondents
      had serious gaps in their knowledge about STIs like acquired immunodeficiency
      syndrome (AIDS), especially its modes of transmission, signs, and symptoms. The
      knowledge of other routes of human immunodeficiency virus (HIV) transmission like
      needle sharing and blood transfusion, and precautionary steps should be given due
      respect in HIV/AIDS awareness programs.

PMID- 28451478
TI  - T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Presented as T-Lymphoid Hyperplasia
      Involving the Central Nervous System.
AB  - We herein report a case of T-cell/histiocyte-rich large B-cell lymphoma which
      initially presented as a self-limiting T-lymphoproliferative disorder involving
      multiple extranodal and extrapulmonary organs, such as the salivary gland, the
      liver, and the central nervous system. Repeated biopsies only revealed polyclonal
      T-lymphocytosis without the presence of atypical B-cells. Angiocentric cellular
      infiltration was absent, thus ruling out lymphomatoid granulomatosis. A
      recurrence in the lymphatic system finally revealed a small population of
      pathognomonic atypical B-cells, which led to the diagnosis. The clinical dilemma
      in the diagnosis and management of this indeterminate condition points to
      limitations in the current nosology.

PMID- 28451479
TI  - Robotic Radiosurgery for Adrenal Gland Metastases.
AB  - INTRODUCTION: The purpose of this study was to investigate the safety and
      efficacy of CyberKnife (CK) robotic radiosurgery for treatment of adrenal
      metastases. METHODS: We performed a retrospective analysis of 23 patients with
      adrenal metastases who had been treated with CK between October 2006 and December
      2015. Fifteen patients received chemotherapy prior to radiosurgery, all patients
      underwent computer tomography (CT) fluoroscopically guided percutaneous placement
      of one to three gold fiducials into the adrenal gland. Nineteen patients were
      selected for single-fraction radiosurgery with a median dose of 22 Gy, four
      patients were treated in three fractions with a median dose of 13.5 Gy. RESULTS:
      Median follow-up time was 23.6 months. Four patients (17%) experienced local
      relapse during the evaluation period with a mean time of 19 months to tumor
      progression. The actuarial local tumor control rate was 95% after one year and
      81% after two years. Three of the four patients with local recurrence were
      retreated with CK radiosurgery. Dynamic tumor tracking enabled accurate treatment
      with correlation errors less than 2 mm, despite extensive respiration-induced
      target motion up to 22 mm. Apart from nausea directly after treatment in five
      patients, we observed no early or late treatment-related side effects.
      CONCLUSIONS: Single fraction robotic radiosurgery for adrenal gland metastases is
      a safe and effective treatment option for patients who are not eligible for
      surgical resection.

PMID- 28451480
TI  - Rare Complications of Cervical Spine Surgery: Horner's Syndrome.
AB  - STUDY DESIGN: A multicenter retrospective case series. OBJECTIVE: Horner's
      syndrome is a known complication of anterior cervical spinal surgery, but it is
      rarely encountered in clinical practice. To better understand the incidence,
      risks, and neurologic outcomes associated with Horner's syndrome, a multicenter
      study was performed to review a large collective experience with this rare
      complication. METHODS: We conducted a retrospective multicenter case series study
      involving 21 high-volume surgical centers from the AOSpine North America Clinical
      Research Network. Medical records for 17 625 patients who received subaxial
      cervical spine surgery from 2005 to 2011 were reviewed to identify occurrence of
      21 predefined treatment complications. Descriptive statistics were provided for
      baseline patient characteristics. Paired t test was used to analyze changes in
      clinical outcomes at follow-up compared to preoperative status. RESULTS: In
      total, 8887 patients who underwent anterior cervical spine surgery at the
      participating institutions were screened. Postoperative Horner's syndrome was
      identified in 5 (0.06%) patients. All patients experienced the complication
      following anterior cervical discectomy and fusion. The sympathetic trunk appeared
      to be more vulnerable when operating on midcervical levels (C5, C6), and most
      patients experienced at least a partial recovery without further treatment.
      CONCLUSIONS: This collective experience suggests that Horner's syndrome is an
      exceedingly rare complication following anterior cervical spine surgery. Injury
      to the sympathetic trunk may be limited by maintaining a midline surgical
      trajectory when possible, and performing careful dissection and retraction of the
      longus colli muscle when lateral exposure is necessary, especially at caudal
      cervical levels.

PMID- 28451481
TI  - Rare Complications of Cervical Spine Surgery: Pseudomeningocoele.
AB  - STUDY DESIGN: This study was a retrospective, multicenter cohort study.
      OBJECTIVES: Rare complications of cervical spine surgery are inherently difficult
      to investigate. Pseudomeningocoele (PMC), an abnormal collection of cerebrospinal
      fluid that communicates with the subarachnoid space, is one such complication. In
      order to evaluate and better understand the incidence, presentation, treatment,
      and outcome of PMC following cervical spine surgery, we conducted a multicenter
      study to pool our collective experience. METHODS: This study was a retrospective,
      multicenter cohort study of patients who underwent cervical spine surgery at any
      level(s) from C2 to C7, inclusive; were over 18 years of age; and experienced a
      postoperative PMC. RESULTS: Thirteen patients (0.08%) developed a postoperative
      PMC, 6 (46.2%) of whom were female. They had an average age of 48.2 years and
      stayed in hospital a mean of 11.2 days. Three patients were current smokers, 3
      previous smokers, 5 had never smoked, and 2 had unknown smoking status. The
      majority, 10 (76.9%), were associated with posterior surgery, whereas 3 (23.1%)
      occurred after an anterior procedure. Myelopathy was the most common indication
      for operations that were complicated by PMC (46%). Seven patients (53%) required
      a surgical procedure to address the PMC, whereas the remaining 6 were treated
      conservatively. All PMCs ultimately resolved or were successfully treated with no
      residual effects. CONCLUSIONS: PMC is a rare complication of cervical surgery
      with an incidence of less than 0.1%. They prolong hospital stay. PMCs occurred
      more frequently in association with posterior approaches. Approximately half of
      PMCs required surgery and all ultimately resolved without residual neurologic or
      other long-term effects.

PMID- 28451482
TI  - Thoracic Duct Injury Following Cervical Spine Surgery: A Multicenter
      Retrospective Review.
AB  - STUDY DESIGN: Multicenter retrospective case series. OBJECTIVE: To determine the
      rate of thoracic duct injury during cervical spine operations. METHODS: A
      retrospective case series study was conducted among 21 high-volume surgical
      centers to identify instances of thoracic duct injury during anterior cervical
      spine surgery. Staff at each center abstracted data for each identified case into
      case report forms. All case report forms were collected by the AOSpine North
      America Clinical Research Network Methodological Core for data processing,
      cleaning, and analysis. RESULTS: Of a total of 9591 patients reviewed that
      underwent cervical spine surgery, 2 (0.02%) incurred iatrogenic injury to the
      thoracic duct. Both patients underwent a left-sided anterior cervical discectomy
      and fusion. The interruption of the thoracic duct was addressed intraoperatively
      in one patient with no residual postoperative effects. The second individual
      developed a chylous fluid collection approximately 2 months after the operation
      that required drainage via needle aspiration. CONCLUSIONS: Damage to the thoracic
      duct during cervical spine surgery is a relatively rare occurrence. Rapid
      identification of the disruption of this lymphatic vessel is critical to minimize
      deleterious effects of this complication.

PMID- 28451483
TI  - Epidural Hematoma Following Cervical Spine Surgery.
AB  - STUDY DESIGN: A multicentered retrospective case series. OBJECTIVE: To determine
      the incidence and circumstances surrounding the development of a symptomatic
      postoperative epidural hematoma in the cervical spine. METHODS: Patients who
      underwent cervical spine surgery between January 1, 2005, and December 31, 2011,
      at 23 institutions were reviewed, and all patients who developed an epidural
      hematoma were identified. RESULTS: A total of 16 582 cervical spine surgeries
      were identified, and 15 patients developed a postoperative epidural hematoma, for
      a total incidence of 0.090%. Substantial variation between institutions was
      noted, with 11 sites reporting no epidural hematomas, and 1 site reporting an
      incidence of 0.76%. All patients initially presented with a neurologic deficit.
      Nine patients had complete resolution of the neurologic deficit after hematoma
      evacuation; however 2 of the 3 patients (66%) who had a delay in the diagnosis of
      the epidural hematoma had residual neurologic deficits compared to only 4 of the
      12 patients (33%) who had no delay in the diagnosis or treatment (P = .53).
      Additionally, the patients who experienced a postoperative epidural hematoma did
      not experience any significant improvement in health-related quality-of-life
      metrics as a result of the index procedure at final follow-up evaluation.
      CONCLUSION: This is the largest series to date to analyze the incidence of an
      epidural hematoma following cervical spine surgery, and this study suggest that
      an epidural hematoma occurs in approximately 1 out of 1000 cervical spine
      surgeries. Prompt diagnosis and treatment may improve the chance of making a
      complete neurologic recovery, but patients who develop this complication do not
      show improvements in the health-related quality-of-life measurements.

PMID- 28451484
TI  - Intraoperative Death During Cervical Spinal Surgery: A Retrospective Multicenter
      Study.
AB  - STUDY DESIGN: A retrospective multicenter study. OBJECTIVE: Routine cervical
      spine surgeries are typically associated with low complication rates, but serious
      complications can occur. Intraoperative death is a very rare complication and
      there is no literature on its incidence. The purpose of this study was to
      determine the intraoperative mortality rates and associated risk factors in
      patients undergoing cervical spine surgery. METHODS: Twenty-one surgical centers
      from the AOSpine North America Clinical Research Network participated in the
      study. Medical records of patients who received cervical spine surgery from
      January 1, 2005, to December 31, 2011, were reviewed to identify occurrence of
      intraoperative death. RESULTS: A total of 258 patients across 21 centers met the
      inclusion criteria. Most of the surgeries were done using the anterior approach
      (53.9%), followed by posterior (39.1%) and circumferential (7%). Average patient
      age was 57.1 +/- 13.2 years, and there were more male patients (54.7% male and
      45.3% female). There was no case of intraoperative death. CONCLUSIONS: Death
      during cervical spine surgery is a very rare complication. In our multicenter
      study, there was a 0% mortality rate. Using an adequate surgical approach for
      patient diagnosis and comorbidities may be the reason how the occurrence of this
      catastrophic adverse event was prevented in our patient population.

PMID- 28451485
TI  - Anterior Cervical Infection: Presentation and Incidence of an Uncommon
      Postoperative Complication.
AB  - STUDY DESIGN: Retrospective multi-institutional case series. OBJECTIVE: The
      anterior cervical discectomy and fusion (ACDF) affords the surgeon the
      flexibility to treat a variety of cervical pathologies, with the majority being
      for degenerative and traumatic indications. Limited data in the literature
      describe the presentation and true incidence of postoperative surgical site
      infections. METHODS: A retrospective multicenter case series study was conducted
      involving 21 high-volume surgical centers from the AOSpine North America Clinical
      Research Network, selected for their excellence in spine care and clinical
      research infrastructure and experience. Medical records for 17 625 patients who
      received cervical spine surgery (levels from C2 to C7) between January 1, 2005,
      and December 31, 2011, inclusive, were reviewed to identify the occurrence of 21
      predefined treatment complications. Patients who underwent an ACDF were
      identified in the database and reviewed for the occurrence of postoperative
      anterior cervical infections. RESULTS: A total of 8887 patients were identified
      from a retrospective database analysis of 21 centers providing data for
      postoperative anterior cervical infections (17/21, 81% response rate). A total of
      6 postoperative infections after ACDF were identified for a mean rate of 0.07%
      (range 0% to 0.39%). The mean age of patients identified was 57.5 (SD = 11.6,
      66.7% female). The mean body mass index was 22.02. Of the total infections, half
      were smokers (n = 3). Two patients presented with myelopathy, and 3 patients
      presented with radiculopathic-type complaints. The mean length of stay was 4.7
      days. All patients were treated aggressively with surgery for management of this
      complication, with improvement in all patients. There were no mortalities.
      CONCLUSION: The incidence of postoperative infection in ACDF is exceedingly low.
      The management has historically been urgent irrigation and debridement of the
      surgical site. However, due to the rarity of this occurrence, guidance for
      management is limited to retrospective series.

PMID- 28451486
TI  - Brachial Plexopathy After Cervical Spine Surgery.
AB  - STUDY DESIGN: Retrospective, multicenter case-series study and literature review.
      OBJECTIVES: To determine the prevalence of brachial plexopathy after cervical
      spine surgery and to review the literature to better understand the etiology and
      risk factors of brachial plexopathy after cervical spine surgery. METHODS: A
      retrospective case-series study of 12 903 patients at 21 different sites was
      performed to analyze the prevalence of several different complications, including
      brachial plexopathy. A literature review of the US National Library of Medicine
      and the National Institutes of Health (PubMed) database was conducted to identify
      articles pertaining to brachial plexopathy following cervical spine surgery.
      RESULTS: In our total population of 12 903 patients, only 1 suffered from
      postoperative brachial plexopathy. The overall prevalence rate was thus 0.01%,
      but the prevalence rate at the site where this complication occurred was 0.07%.
      Previously reported risk factors for postoperative brachial plexopathy include
      age, anterior surgical procedures, and a diagnosis of ossification of the
      posterior longitudinal ligament. The condition can also be due to patient
      positioning during surgery, which can generally be detected via the use of
      intraoperative neuromonitoring. CONCLUSIONS: Brachial plexopathy following
      cervical spine surgery is rare and merits further study.

PMID- 28451487
TI  - Epidemiology and Outcomes of Vertebral Artery Injury in 16 582 Cervical Spine
      Surgery Patients: An AOSpine North America Multicenter Study.
AB  - STUDY DESIGN: A multicenter retrospective case series was compiled involving 21
      medical institutions. Inclusion criteria included patients who underwent cervical
      spine surgery between 2005 and 2011 and who sustained a vertebral artery injury
      (VAI). OBJECTIVE: To report the frequency, risk factors, outcomes, and management
      goals of VAI in patients who have undergone cervical spine surgery. METHODS:
      Patients were evaluated on the basis of condition-specific functional status
      using the Neck Disability Index (NDI), modified Japanese Orthopaedic Association
      (mJOA) score, the Nurick scale, and the 36-Item Short-Form Health Survey (SF-36).
      RESULTS: VAIs were identified in a total of 14 of 16 582 patients screened (8.4
      per 10 000). The mean age of patients with VAI was 59 years (+/-10) with a female
      predominance (78.6%). Patient diagnoses included myelopathy, radiculopathy,
      cervical instability, and metastatic disease. VAI was associated with substantial
      blood loss (770 mL), although only 3 cases required transfusion. Of the 14 cases,
      7 occurred with an anterior-only approach, 3 cases with posterior-only approach,
      and 4 during circumferential approach. Fifty percent of cases of VAI with
      available preoperative imaging revealed anomalous vessel anatomy during
      postoperative review. Average length of hospital stay was 10 days (+/-8).
      Notably, 13 of the 14 (92.86%) cases resolved without residual deficits. Compared
      to preoperative baseline NDI, Nurick, mJOA, and SF-36 scores for these patients,
      there were no observed changes after surgery (P = .20-.94). CONCLUSIONS:
      Vertebral artery injuries are potentially catastrophic complications that can be
      sustained from anterior or posterior cervical spine approaches. The data from
      this study suggest that with proper steps to ensure hemostasis, patients recover
      function at a high rate and do not exhibit residual deficits.

PMID- 28451489
TI  - Hypoglossal Nerve Palsy After Cervical Spine Surgery.
AB  - STUDY DESIGN: Multi-institutional retrospective study. OBJECTIVE: The goal of the
      current study is to quantify the incidence of 2 extremely rare complications of
      cervical spine surgery; hypoglossal and glossopharyngeal nerve palsies. METHODS:
      A total of 8887 patients who underwent cervical spine surgery from 2005 to 2011
      were included in the study from 21 institutions. RESULTS: No glossopharyngeal
      nerve injuries were reported. One hypoglossal nerve injury was reported after a
      C3-7 laminectomy (0.01%). This deficit resolved with conservative management. The
      rate by institution ranged from 0% to 1.28%. Although not directly injured by the
      surgical procedure, the transient nerve injury might have been related to patient
      positioning as has been described previously in the literature. CONCLUSIONS:
      Hypoglossal nerve injury during cervical spine surgery is an extremely rare
      complication. Institutional rates may vary. Care should be taken during posterior
      cervical surgery to avoid hyperflexion of the neck and endotracheal tube
      malposition.

PMID- 28451490
TI  - Incidence and Outcomes of Acute Implant Extrusion Following Anterior Cervical
      Spine Surgery.
AB  - STUDY DESIGN: Multi-institutional retrospective case series of 8887 patients who
      underwent anterior cervical spine surgery. OBJECTIVE: Anterior decompression from
      discectomy or corpectomy is not without risk. Surgical morbidity ranges from 9%
      to 20% and is likely underreported. Little is known of the incidence and effects
      of rare complications on functional outcomes following anterior spinal surgery.
      In this retrospective review, we examined implant extrusions (IEs) following
      anterior cervical fusion. METHODS: A retrospective multicenter case series study
      involving 21 high-volume surgical centers from the AOSpine North America Clinical
      Research Network. Medical records for 17 625 patients who received cervical spine
      surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011,
      were reviewed to identify occurrence of 21 predefined treatment complications.
      RESULTS: Following anterior cervical fusion, the incidence of IE ranged from 0.0%
      to 0.8% across 21 institutions with 11 cases reported. All surgeries involved
      multiple levels, and 7/11 (64%) involved either multilevel corpectomies or hybrid
      constructs with at least one adjacent discectomy to a corpectomy. In 7/11 (64%)
      patients, constructs ended with reconstruction or stabilization at C7. Nine
      patients required surgery for repair and stabilization following IE. Average
      length of hospital stay after IE was 5.2 days. Only 2 (18%) had residual deficits
      after reoperation. CONCLUSIONS: IE is a very rare complication after anterior
      cervical spine surgery often requiring revision. Constructs requiring multilevel
      reconstruction, especially at the cervicothoracic junction, have a higher risk
      for failure, and surgeons should proceed with caution in using an anterior-only
      approach in these demanding cases. Surgeons can expect most patients to regain
      function after reoperation.

PMID- 28451488
TI  - Esophageal Perforation Following Anterior Cervical Spine Surgery: Case Report and
      Review of the Literature.
AB  - STUDY DESIGN: Multicenter retrospective case series and review of the literature.
      OBJECTIVE: To determine the rate of esophageal perforations following anterior
      cervical spine surgery. METHODS: As part of an AOSpine series on rare
      complications, a retrospective cohort study was conducted among 21 high-volume
      surgical centers to identify esophageal perforations following anterior cervical
      spine surgery. Staff at each center abstracted data from patients' charts and
      created case report forms for each event identified. Case report forms were then
      sent to the AOSpine North America Clinical Research Network Methodological Core
      for data processing and analysis. RESULTS: The records of 9591 patients who
      underwent anterior cervical spine surgery were reviewed. Two (0.02%) were found
      to have esophageal perforations following anterior cervical spine surgery. Both
      cases were detected and treated in the acute postoperative period. One patient
      was successfully treated with primary repair and debridement. One patient
      underwent multiple debridement attempts and expired. CONCLUSIONS: Esophageal
      perforation following anterior cervical spine surgery is a relatively rare
      occurrence. Prompt recognition and treatment of these injuries is critical to
      minimizing morbidity and mortality.

PMID- 28451491
TI  - Misplaced Cervical Screws Requiring Reoperation.
AB  - STUDY DESIGN: A multicenter, retrospective case series. OBJECTIVE: In the past
      several years, screw fixation of the cervical spine has become commonplace. For
      the most part, this is a safe, low-risk procedure. While rare, screw backout or
      misplaced screws can lead to morbidity and increased costs. We report our
      experiences with this uncommon complication. METHODS: A multicenter,
      retrospective case series was undertaken at 23 institutions in the United States.
      Patients were included who underwent cervical spine surgery from January 1, 2005,
      to December 31, 2011, and had misplacement of screws requiring reoperation.
      Institutional review board approval was obtained at all participating
      institutions, and detailed records were sent to a central data center. RESULTS: A
      total of 12 903 patients met the inclusion criteria and were analyzed. There were
      11 instances of screw backout requiring reoperation, for an incidence of 0.085%.
      There were 7 posterior procedures. Importantly, there were no changes in the
      health-related quality-of-life metrics due to this complication. There were no
      new neurologic deficits; a patient most often presented with pain, and
      misplacement was diagnosed on plain X-ray or computed tomography scan. The most
      common location for screw backout was C6 (36%). CONCLUSIONS: This study
      represents the largest series to tabulate the incidence of misplacement of screws
      following cervical spine surgery, which led to revision procedures. The data
      suggest this is a rare event, despite the widespread use of cervical fixation.
      Patients suffering this complication can require revision, but do not usually
      suffer neurologic sequelae. These patients have increased cost of care.
      Meticulous technique and thorough knowledge of the relevant anatomy are the best
      means of preventing this complication.

PMID- 28451492
TI  - Recurrent Laryngeal Nerve Palsy After Cervical Spine Surgery: A Multicenter
      AOSpine Clinical Research Network Study.
AB  - STUDY DESIGN: Multicenter retrospective study. OBJECTIVES: To investigate the
      risk of symptomatic recurrent laryngeal nerve palsy (RLNP) following cervical
      spine surgery, to examine risk factors for its development, and to report its
      treatment and outcomes. METHODS: A multicenter study from 21 high-volume surgical
      centers from the AOSpine North America Clinical Research Network was performed.
      Each center screened for rare complications following cervical spine surgery,
      including RLNP. Patients were included if they underwent cervical spine surgery
      (levels from C2 to C7) between January 1, 2005 and December 31, 2011. Data were
      analyzed with regard to complication treatment and outcome. Cases were compared
      to a control group from the AOSpine CSM and CSM-I studies. RESULTS: Three centers
      reported 19 cases of RLNP from a cohort of 1345 patients. The reported incidence
      of RLNP ranged from 0.6% to 2.9% between these 3 centers. Fifteen patients (79%)
      in the RLNP group were approached from the left side. Ten patients (52.6%)
      required treatment for RLNP-6 required medical therapy (steroids), 1
      interventional treatment (injection laryngoplasty), and 3 conservative therapy
      (speech therapy). When examining outcomes, 73.7% (14/19) of cases resolved
      completely, 15.8% (3/19) resolved with residual effects, and in 10.5% (2/19) of
      cases this could not be determined. CONCLUSIONS: In this multicenter study
      examining rare complications following cervical spine surgery, the risk of RLNP
      after cervical spine surgery ranged from 0.6% to 2.9% between centers. Though
      rare, it was found that 16% of patients may experience partial resolution with
      residual effects, and 74% resolve completely.

PMID- 28451495
TI  - Rare Complications of Cervical Spine Surgery.

PMID- 28451493
TI  - A Multicenter Study of the Presentation, Treatment, and Outcomes of Cervical
      Dural Tears.
AB  - STUDY DESIGN: Retrospective multicenter case series study. OBJECTIVE: Because
      cervical dural tears are rare, most surgeons have limited experience with this
      complication. A multicenter study was performed to better understand the
      presentation, treatment, and outcomes following cervical dural tears. METHODS:
      Multiple surgeons from 23 institutions retrospectively identified 21 rare
      complications that occurred between 2005 and 2011, including unintentional
      cervical dural tears. Demographic data and surgical history were obtained.
      Clinical outcomes following surgery were assessed, and any reoperations were
      recorded. Neck Disability Index (NDI), modified Japanese Orthopaedic Association
      (mJOA), Nurick classification (NuC), and Short-Form 36 (SF36) scores were
      recorded at baseline and final follow-up at certain centers. All data were
      collected, collated, and analyzed by a private research organization. RESULTS:
      There were 109 cases of cervical dural tears among 18 463 surgeries performed. In
      101 cases (93%) there was no clinical sequelae following successful dural tear
      repair. There were statistical improvements (P < .05) in mJOA and NuC scores, but
      not NDI or SF36 scores. No specific baseline or operative factors were found to
      be associated with the occurrence of dural tears. In most cases, no further
      postoperative treatments of the dural tear were required, while there were 13
      patients (12%) that required subsequent treatment of cerebrospinal fluid
      drainage. Analysis of those requiring further treatments did not identify an
      optimum treatment strategy for cervical dural tears. CONCLUSIONS: In this
      multicenter study, we report our findings on the largest reported series (n =
      109) of cervical dural tears. In a vast majority of cases, no subsequent
      interventions were required and no clinical sequelae were observed.

PMID- 28451496
TI  - Carotid Artery Injury in Anterior Cervical Spine Surgery: Multicenter Cohort
      Study and Literature Review.
AB  - STUDY DESIGN: Retrospective study and literature review. OBJECTIVE: To provide
      more comprehensive data about carotid artery injury (CAI) or cerebrovascular
      accident (CVA) related to anterior cervical spine surgery. METHODS: We conducted
      a retrospective, multicenter, case series study involving 21 high-volume surgical
      centers from the AOSpine North America Clinical Research Network. Medical records
      of 17 625 patients who went through cervical spine surgery (levels from C2 to C7)
      between January 1, 2005, and December 31, 2011, were analyzed. Also, we performed
      a literature review using Medline and PubMed databases. The following terms were
      used alone, and in combination, to search for relevant articles: cervical, spine,
      surgery, complication, iatrogenic, carotid artery, injury, cerebrovascular
      accident, CVA, and carotid stenosis. RESULTS: Among 17 625 patients that were
      analyzed, no cases were reported to experienced CAI or CVA after cervical spine
      surgery. Nevertheless, in our PubMed search we found 157 articles, but only 5
      articles matched our study objective criteria; 2 cases were reported to present
      CAI and 3 cases presented CVA. CONCLUSIONS: CAI and CVA related to anterior
      cervical spine surgeries are extremely rare. We were not able to find neither in
      our retrospective study nor in our literature research a correlation between the
      type or length of anterior cervical spine procedure with CVA or CAI
      complications. However, surgeons should be aware of the possibility of vascular
      complications and minimize intraoperative direct vascular manipulations or
      retraction. Preoperative screening for underlying vascular pathology and risk
      factors is also important.

PMID- 28451494
TI  - C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59
      Cases.
AB  - STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical
      spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of
      cervical decompressive spinal surgery. The goal of this study was to review the
      incidence, patient characteristics, and outcome of C5 palsy in patients
      undergoing cervical spine surgery. METHODS: We conducted a multicenter,
      retrospective review of 13 946 patients across 21 centers who received cervical
      spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011,
      inclusive. P values were calculated using 2-sample t test for continuous
      variables and chi2 tests or Fisher exact tests for categorical variables.
      RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5
      palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most
      recent follow-up, 32 patients reported complete resolution of symptoms (54.2%),
      15 had symptoms resolve with residual effects (25.4%), 10 patients did not
      recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy
      occurred in all surgical approaches and across a variety of diagnoses. The
      majority of patients had full recovery or recovery with residual effects. This
      study represents the largest series of North American patients reviewed to date.

PMID- 28451497
TI  - Evaluation of Adverse Events in Total Disc Replacement: A Meta-Analysis of FDA
      Summary of Safety and Effectiveness Data.
AB  - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The safety of new
      technology such as cervical total disc replacement (TDR) is of paramount
      importance and is best evaluated in randomized clinical trials (RCT). We compared
      complication risks of TDR to fusion using data from Investigational Device
      Exemptions. METHODS: A systematic review of FDA Summary of Safety and
      Effectiveness reports of the 8 approved cervical TDRs was performed. These were
      all randomized controlled trials comparing anterior cervical discectomy and
      fusion (ACDF) to TDR. Important outcome variables were dysphagia, wound
      infection, neurologic injuries, heterotopic ossification, death, and secondary
      surgeries. A random effects model was selected a priori. Data on adverse events
      was abstracted and analyzed by calculating relative risk of ACDF to TDR by meta
      analysis techniques. RESULTS: The study included 3027 patients with 1377
      randomized to ACDF and 1652 to TDR. No statistical differences were present
      between the 2 groups in dysphagia/dysphonia, hardware related, heterotopic
      ossification, death, and overall neurologic adverse events and incidence of
      neurologic deterioration. The relative risk of wound-related problems ACDF to TDR
      was 0.76 (95% confidence interval [CI] = 0.59, 0.98) favoring ACDF, which was
      statistically significant, but these were minor and never required a second
      surgical procedure for deep wound infection. The relative risk of ACDF to TDR in
      surgical-related neurologic events and secondary surgeries was 1.62 (95% CI =
      1.04, 2.53) and 1.79 (95% CI = 1.17, 2.74), both favoring TDR. CONCLUSIONS:
      Cervical TDR appears to be as safe as or safer than ACDF at 2-year follow-up.

PMID- 28451498
TI  - A Multicenter Review of Superior Laryngeal Nerve Injury Following Anterior
      Cervical Spine Surgery.
AB  - STUDY DESIGN: A retrospective multicenter case-series study; case report and
      review of the literature. OBJECTIVE: The anatomy and function of the superior
      laryngeal nerve (SLN) are well described; however, the consequences of SLN injury
      remain variable and poorly defined. The prevalence of SLN injury as a consequence
      of cervical spine surgery is difficult to discern as its clinical manifestations
      are often inconstant and frequently of a subclinical degree. A multicenter study
      was performed to better delineate the risk factors, prevalence, and outcomes of
      SLN injury. METHODS: A retrospective multicenter case-series study involving 21
      high-volume surgical centers from the AO Spine North America Clinical Research
      Network. Medical records for 17 625 patients who received subaxial cervical spine
      surgery from 2005 to 2011 were reviewed to identify occurrence of 21 predefined
      treatment complications. Descriptive statistics were provided for baseline
      patient characteristics. A retrospective review of the neurosurgical literature
      on SLN injury was also performed. RESULTS: A total of 8887 patients who underwent
      anterior cervical spine surgery at the participating institutions were screened,
      and 1 case of SLN palsy was identified. The prevalence ranged from 0% to 1.25%
      across all centers. The patient identified underwent a C4 corpectomy. The SLN
      injury was identified after the patient demonstrated difficulty swallowing
      postoperatively. He underwent placement of a percutaneous gastrostomy tube and
      his SLN palsy resolved by 6 weeks. CONCLUSIONS: This multicenter study
      demonstrates that identification of SLN injury occurs very infrequently.
      Symptomatic SLN injury is an exceedingly rare complication of anterior cervical
      spine surgery. The SLN is particularly vulnerable when exposing the more rostral
      levels of the cervical spine. Careful dissection and retraction of the longus
      coli may decrease the risk of SLN injury during anterior cervical surgery.

PMID- 28451499
TI  - Iatrogenic Spinal Cord Injury Resulting From Cervical Spine Surgery.
AB  - STUDY DESIGN: Retrospective cohort study of prospectively collected data.
      OBJECTIVE: To examine the incidence of iatrogenic spinal cord injury following
      elective cervical spine surgery. METHODS: A retrospective multicenter case series
      study involving 21 high-volume surgical centers from the AOSpine North America
      Clinical Research Network was conducted. Medical records for 17 625 patients who
      received cervical spine surgery (levels from C2 to C7) between January 1, 2005,
      and December 31, 2011, were reviewed to identify occurrence of iatrogenic spinal
      cord injury. RESULTS: In total, 3 cases of iatrogenic spinal cord injury
      following cervical spine surgery were identified. Institutional incidence rates
      ranged from 0.0% to 0.24%. Of the 3 patients with quadriplegia, one underwent
      anterior-only surgery with 2-level cervical corpectomy, one underwent anterior
      surgery with corpectomy in addition to posterior surgery, and one underwent
      posterior decompression and fusion surgery alone. One patient had complete
      neurologic recovery, one partially recovered, and one did not recover motor
      function. CONCLUSION: Iatrogenic spinal cord injury following cervical spine
      surgery is a rare and devastating adverse event. No standard protocol exists that
      can guarantee prevention of this complication, and there is a lack of consensus
      regarding evaluation and treatment when it does occur. Emergent imaging with
      magnetic resonance imaging or computed tomography myelography to evaluate for
      compressive etiology or malpositioned instrumentation and avoidance of
      hypotension should be performed in cases of intraoperative and postoperative
      spinal cord injury.

PMID- 28451500
TI  - Perioperative Vision Loss in Cervical Spinal Surgery.
AB  - STUDY DESIGN: Retrospective multicenter case series. OBJECTIVE: To assess the
      rate of perioperative vision loss following cervical spinal surgery. METHODS:
      Medical records for 17 625 patients from 21 high-volume surgical centers from the
      AOSpine North America Clinical Research Network who received cervical spine
      surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011,
      inclusive, were reviewed to identify occurrences of vision loss following
      surgery. RESULTS: Of the 17 625 patients in the registry, there were 13 946
      patients assessed for the complication of blindness. There were 9591 cases that
      involved only anterior surgical approaches; the remaining 4355 cases were
      posterior and/or circumferential fusions. There were no cases of blindness or
      vision loss in the postoperative period reported during the sampling period.
      CONCLUSIONS: Perioperative vision loss following cervical spinal surgery is
      exceedingly rare.

PMID- 28451502
TI  - Editorial.

PMID- 28451501
TI  - Prevalence and Outcomes in Patients Undergoing Reintubation After Anterior
      Cervical Spine Surgery: Results From the AOSpine North America Multicenter Study
      on 8887 Patients.
AB  - STUDY DESIGN: A multicenter, retrospective cohort study. OBJECTIVE: To evaluate
      clinical outcomes in patients with reintubation after anterior cervical spine
      surgery. METHODS: A total of 8887 patients undergoing anterior cervical spine
      surgery were enrolled in the AOSpine North America Rare Complications of Cervical
      Spine Surgery study. Patients with or without complications after surgery were
      included. Demographic and surgical information were collected for patients with
      reintubation. Patients were evaluated using a variety of assessment tools,
      including the modified Japanese Orthopedic Association scale, Nurick score, Neck
      Disability Index, and Short Form-36 Health Survey. RESULTS: Nine cases of
      postoperative reintubation were identified. The total prevalence of this
      complication was 0.10% and ranged from 0% to 0.59% across participating
      institutions. The time to development of airway symptoms after surgery was within
      24 hours in 6 patients and between 5 and 7 days in 3 patients. Although 8
      patients recovered, 1 patient died. At final follow-up, patients with
      reintubation did not exhibit significant and meaningful improvements in pain,
      functional status, or quality of life. CONCLUSIONS: Although the prevalence of
      reintubation was very low, this complication was associated with adverse clinical
      outcomes. Clinicians should identify their high-risk patients and carefully
      observe them for up to 2 weeks after surgery.

PMID- 28451503
TI  - Rapid Worsening of Symptoms and High Cell Proliferative Activity in Intra- and
      Extramedullary Spinal Hemangioblastoma: A Need for Earlier Surgery.
AB  - STUDY DESIGN: A retrospective analysis of a prospective database. OBJECTIVE: To
      compare preoperative symptoms, ambulatory ability, intraoperative spinal cord
      monitoring, and pathologic cell proliferation activity between intramedullary
      only and intramedullary plus extramedullary hemangioblastomas, with the goal of
      determining the optimal timing for surgery. METHODS: The subjects were 28
      patients (intramedullary only in 23 cases [group I] and intramedullary plus
      extramedullary in 5 cases [group IE]) who underwent surgery for spinal
      hemangioblastoma. Preoperative symptoms, ambulatory ability on the McCormick
      scale, intraoperative spinal cord monitoring, and pathologic findings using Ki67
      were compared between the groups. RESULTS: In group IE, preoperative motor
      paralysis was significantly higher (100 versus 26%, p < 0.005), the mean period
      from initial symptoms to motor paralysis was significantly shorter (3.5 versus
      11.9 months, p < 0.05), and intraoperative spinal cord monitoring aggravation was
      higher (65 versus 6%, p < 0.05). All 5 patients without total resection in group
      I underwent reoperation. Ki67 activity was higher in group IE (15% versus 1%, p <
      0.05). Preoperative ambulatory ability was significantly poorer in group IE (p <
      0.05), but all cases in this group improved after surgery, and postoperative
      ambulatory ability did not differ significantly between the two groups.
      CONCLUSIONS: Intramedullary plus extramedullary spinal hemangioblastoma is
      characterized by rapid preoperative progression of symptoms over a short period,
      severe spinal cord damage including preoperative motor paralysis, and poor gait
      ability compared with an intramedullary tumor only. Earlier surgery with
      intraoperative spinal cord monitoring is recommended for total resection and good
      surgical outcome especially for an IE tumor compared with an intramedullary
      tumor.

PMID- 28451504
TI  - The Regenerative Potential of Notochordal Cells in a Nucleus Pulposus Explant.
AB  - STUDY DESIGN: In vitro disk explant culture. OBJECTIVE: Notochordal cells (NCs)
      have been shown to upregulate matrix production by nucleus pulposus (NP) cells in
      coculture. To examine the translation of these in vitro results to a nativelike
      setting, the regenerative potential of NCs injected into NP tissue was assessed
      in this study. METHODS: NP explants were cultured after injection with NCs in
      phosphate-buffered saline (PBS) or with PBS alone (sham). At days 0 and 42, cell
      viability and morphology, water, DNA, sulfated glycosaminoglycan and
      hydroxyproline content, and gene expression of anabolic markers were analyzed.
      RESULTS: NCs remained viable during culture, but their morphology changed. The
      biochemical content remained unchanged, except for the DNA content in the NC
      group. Overall ACAN expression remained unchanged, whereas COL2A1 decreased
      during culture. CONCLUSIONS: No overall anabolic response was observed when NCs
      were injected into NP explants. NCs were found to survive but did not display the
      typical NC morphology by the end of the culture period.

PMID- 28451505
TI  - Facet Effusion without Radiographic Instability Has No Effect on the Outcome of
      Minimally Invasive Decompression Surgery.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Lumbar segmental instability
      is a key factor determining whether decompression alone or decompression and
      fusion surgery is required to treat lumbar spinal stenosis (LSS). Some recent
      reports have suggested that facet joint effusion is correlated with spinal
      segmental instability. The aim of this study is to report the effect of facet
      effusion without radiographic segmental instability on the outcome of less
      invasive decompression surgery for LSS. METHODS: Seventy-nine patients with LSS
      (32 women, mean age: 69.1 +/- 9.1 years) who had no segmental instability on
      dynamic radiographs before undergoing L4-L5 microsurgical decompression and who
      were followed for at least 2 years postoperatively were analyzed. They were
      divided into three groups on the basis of the existence and size of L4-L5 facet
      effusion using preoperative magnetic resonance imaging: grade 0 had no effusion
      (n = 31), grade 1 had measurable effusion (n = 35), and grade 2 had large
      effusion (n = 13). Japanese Orthopedics Association (JOA) score, visual analog
      scale (VAS), and the Short-Form (SF)-36 scores were recorded preoperatively and
      12 and 24 months postoperatively. RESULTS: JOA score; VAS of low back pain, leg
      pain, and numbness; and SF-36 (physical component summary and mental component
      summary) scores did not differ significantly between the three groups in every
      terms (p = 0.921, 0.996, 0.950, 0.693, 0.374, 0.304, and 0.624, respectively, at
      final follow-up). CONCLUSION: In the absence of radiographic instability, facet
      joint effusion has no effect on the outcome of less-invasive decompression
      surgery.

PMID- 28451506
TI  - Complications after Fusion for Thoracolumbar Fractures in Patients with
      Ankylosing Spondylitis.
AB  - STUDY DESIGN: Retrospective analysis of a Medicare database (2005 to 2012).
      OBJECTIVE: To study postoperative complication rates following thoracolumbar
      fusion for traumatic thoracolumbar fracture in patients with ankylosing
      spondylitis (AS) compared with patients without AS. METHODS: The PearlDiver
      database (2005 to 2012) was queried to examine postoperative complication rates
      in patients with AS undergoing posterior thoracolumbar fusion for thoracolumbar
      fracture (n  =  968). Complication rates were compared with proportion-matched
      controls without AS undergoing the same procedure (n  =  1,979). We examined and
      compared the incidence of death, postoperative infection, transfusion, venous
      thromboembolism, respiratory failure, pneumonia, myocardial infarction, urinary
      tract infection, and acute renal failure in each cohort within 90 days
      postoperatively. RESULTS: Patients with AS had significantly higher rates of
      surgical site infection (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2 to
      2.2, p  =  0.002), day-of-surgery transfusion rates (OR 1.5, 95% CI 1.3 to 1.8, p
      < 0.0001), respiratory failure (OR 1.8, 95% CI 1.3 to 2.5, p  =  0.0006),
      pneumonia (OR 1.8, 95% CI 1.3 to 2.5, p  =  0.0002), acute renal failure (OR 1.6,
      95% CI 1.2 to 2.3, p  =  0.005), and total medical complications (OR 1.5, 95% CI
      1.2 to 1.9, p < 0.0001). Ninety-day mortality was not different between the two
      cohorts (p  =  0.18). CONCLUSIONS: Thoracolumbar fusion for thoracolumbar
      fracture in patients with AS is associated with increased rates of surgical site
      infection, transfusion, respiratory failure, pneumonia, and acute renal failure
      postoperatively compared with patients without AS. The level of evidence in this
      study was III.

PMID- 28451507
TI  - Assessment of a Learning Strategy among Spine Surgeons.
AB  - STUDY DESIGN: Pilot test, observational study. OBJECTIVE: To evaluate objectively
      the knowledge transfer provided by theoretical and practical activities during
      AOSpine courses for spine surgeons. METHODS: During two AOSpine principles
      courses, 62 participants underwent precourse assessment, which consisted of
      questions about their professional experience, preferences regarding adolescent
      idiopathic scoliosis (AIS) classification, and classifying the curves by means of
      the Lenke classification of two AIS clinical cases. Two learning strategies were
      used during the course. A postcourse questionnaire was applied to reclassify the
      same deformity cases. Differences in the correct answers of clinical cases
      between pre- and postcourse were analyzed, revealing the number of participants
      whose accuracy in classification improved after the course. RESULTS: Analysis
      showed a decrease in the number of participants with wrong answers in both cases
      after the course. In the first case, statistically significant differences were
      observed in both curve pattern (83.3%, p  =  0.005) and lumbar spine modifier
      (46.6%, p  =  0.049). No statistically significant improvement was seen in the
      sagittal thoracic modifier (33.3%, p  =  0.309). In the second case, statistical
      improvement was obtained in curve pattern (27.4%, p  =  0.018). No statistically
      significant improvement was seen regarding lumbar spine modifier (9.8%, p  = 
      0.121) and sagittal thoracic modifier (12.9%, p  =  0.081). CONCLUSION: This
      pilot test showed objectively that learning strategies used during AOSpine
      courses improved the participants' knowledge. Teaching strategies must be
      continually improved to ensure an optimal level of knowledge transfer.

PMID- 28451508
TI  - Thirty-Day Morbidity Associated with Pelvic Fixation in Adult Patients Undergoing
      Fusion for Spinal Deformity: A Propensity-Matched Analysis.
AB  - STUDY DESIGN: Retrospective study of prospectively collected data. OBJECTIVE: To
      determine if patients undergoing spinal deformity surgery with pelvic fixation
      are at an increased risk of morbidity. METHODS: The American College of Surgeons
      National Surgical Quality Improvement Program is a large multicenter clinical
      registry that prospectively collects preoperative risk factors, intraoperative
      variables, and 30-day postoperative morbidity and mortality outcomes from ~400
      hospitals nationwide. Current Procedural Terminology codes were used to query the
      database between 2010 and 2014 for adults who underwent fusion for spinal
      deformity. Patients were separated into groups of those with and without pelvic
      fixation. Univariate analysis and multivariate logistic regression were used to
      analyze the effect of pelvic fixation on the incidence of postoperative morbidity
      and other surgical outcomes. RESULTS: Multivariate analysis showed that pelvic
      fixation was a significant predictor of overall morbidity (odds ratio [OR] = 2.3,
      95% confidence interval [CI]: 1.7 to 3.1, p = 0.0002), intra- or postoperative
      blood transfusion (OR = 2.3, 95% CI: 1.7 to 3.1 p < 0.0001), extended operative
      time (OR = 4.7, 95% CI: 3.1 to 7.0 p < 0.0001), and length of stay > 5 days (OR =
      2.1, 95% CI 1.5 to 2.8, p < 0.0001) in patients undergoing fusion for spinal
      deformity. However, fusion to the pelvis did not lead to additional risk for
      other complications, including wound complications (p = 0.3191). CONCLUSION:
      Adult patients undergoing spinal deformity surgery with pelvic fixation were not
      susceptible to increased morbidity beyond increased blood loss, greater operative
      time, and extended length of stay.

PMID- 28451509
TI  - Hybrid Instrumentation in Lumbar Spinal Fusion: A Biomechanical Evaluation of
      Three Different Instrumentation Techniques.
AB  - STUDY DESIGN: Ex vivo human cadaveric study. OBJECTIVE: The development or
      progression of adjacent segment disease (ASD) after spine stabilization and
      fusion is a major problem in spine surgery. Apart from optimal balancing of the
      sagittal profile, dynamic instrumentation is often suggested to prevent or impede
      ASD. Hybrid instrumentation is used to gain stabilization while allowing motion
      to avoid hypermobility in the adjacent segment. In this biomechanical study, the
      effects of two different hybrid instrumentations on human cadaver spines were
      evaluated and compared with a rigid instrumentation. METHODS: Eighteen human
      cadaver spines (T11-L5) were subdivided into three groups: rigid, dynamic, and
      hook comprising six spines each. Clinical parameters and initial mechanical
      characteristics were consistent among groups. All specimens received rigid
      fixation from L3-L5 followed by application of a free bending load of extension
      and flexion. The range of motion (ROM) for every segment was evaluated. For the
      rigid group, further rigid fixation from L1-L5 was applied. A dynamic Elaspine
      system (Spinelab AG, Winterthur, Switzerland) was applied from L1 to L3 for the
      dynamic group, and the hook group was instrumented with additional laminar hooks
      at L1-L3. ROM was then evaluated again. RESULTS: There was no significant
      difference in ROM among the three instrumentation techniques. CONCLUSION: Based
      on this data, the intended advantage of a hybrid or dynamic instrumentation might
      not be achieved.

PMID- 28451510
TI  - Assessment of the Learning Curve for Microendoscopic Decompression Surgery for
      Lumbar Spinal Canal Stenosis through an Analysis of 480 Cases Involving a Single
      Surgeon.
AB  - STUDY DESIGN:  Retrospective study. OBJECTIVE:  To assess the learning curve of
      microendoscopic decompression surgery for lumbar spinal canal stenosis (LSCS).
      METHODS:  Four hundred eighty LSCS cases involving 753 stenotic lesions limited
      to the intraspinal canal were treated with microendoscopic decompression by a
      single surgeon at an institution between November 2006 and January 2015. They
      were numbered chronologically, and the operating time, intraoperative blood loss,
      and perioperative complications were investigated. Surgical outcomes were
      evaluated using the Japanese Orthopedic Association (JOA) score for low back pain
      before and 1 year after the operation. RESULTS:  The mean operating time per
      level was 66.1 minutes. There was a progressive reduction in the operating time
      through the case series, and the approximate curve seemed to be y =  - 9.4Ln(x) +
      115.0. The blood loss per level, which showed a mean value of 15.0 mL, was more
      than 50 mL in only 2.7% of the cases after case no. 30 and in 20% of the cases
      before it. There were 10 (2.1%) cases of perioperative complications, which
      occurred even after the surgeon had gained mastery of the procedure. The median
      JOA score improved significantly from 17 points preoperatively to 26 points
      postoperatively. CONCLUSIONS:  The learning curve of microendoscopic
      decompression surgery for LSCS has been defined with data for a single surgeon in
      an institution. The operating time seems to decrease along a natural logarithmic
      function. The intraoperative blood loss stabilizes after the first 30 cases,
      whereas perioperative complications can occur at any time even after mastery of
      the technique.

PMID- 28451511
TI  - Autograft versus Allograft for Cervical Spinal Fusion: A Systematic Review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To compare the effectiveness and
      safety between iliac crest bone graft (ICBG), non-ICBG autologous bone, and
      allograft in cervical spine fusion. To avoid problems at the donor site, various
      allograft materials have been used as a substitute for autograft. However, there
      are still questions as to the comparative effectiveness and safety of cadaver
      allograft compared with autologous ICBG. METHODS: A systematic search of multiple
      major medical reference databases was conducted to identify studies evaluating
      spinal fusion in patients with cervical degenerative disk disease using ICBG
      compared with non-ICBG autograft or allograft or non-ICBG autograft compared with
      allograft in the cervical spine. Radiographic fusion, patient-reported outcomes,
      and functional outcomes were the primary outcomes of interest. Adverse events
      were evaluated for safety. RESULTS: The search identified 13 comparative studies
      that met our inclusion criteria: 2 prospective cohort studies and 11
      retrospective cohort studies. Twelve cohort studies compared allograft with ICBG
      autograft during anterior cervical fusion and demonstrated with a low evidence
      level of support that there are no differences in fusion percentages, pain
      scores, or functional results. There was insufficient evidence comparing patients
      receiving allograft with non-ICBG autograft for fusion, pain, revision, and
      functional and safety outcomes. No publications directly comparing non-ICBG
      autograft with ICBG were found. CONCLUSION: Although the available literature
      suggests ICBG and allograft may have similar effectiveness in terms of fusion
      rates, pain scores, and functional outcomes following anterior cervical fusion,
      there are too many limitations in the available literature to draw any
      significant conclusions. No individual study provided greater than class III
      evidence, and when evaluating the overall body of literature, no conclusion had
      better than low evidence support. A prospective randomized trial with adequate
      sample size to compare fusion rates, efficacy measures, costs, and safety is
      warranted.

PMID- 28451512
TI  - Spinal Compression Fracture Management: A Review of Current Treatment Strategies
      and Possible Future Avenues.
AB  - STUDY DESIGN: Narrative review. OBJECTIVE: Despite the numerous treatment options
      for vertebral compression fractures, a consensus opinion for the management of
      patients with these factures has not been established. This review is meant to
      provide an up-to-date overview of the most common treatment strategies for
      compression fractures and to suggest possible routes for the development of
      clearer treatment guidelines. METHODS: A comprehensive database search of PubMed
      was performed. All results from the past 30 years were obtained and evaluated
      based on title and abstract. The full length of relevant studies was analyzed for
      level of evidence, and the strongest studies were used in this review. RESULTS:
      The major treatment strategies for patients with compression fractures are
      conservative pain management and vertebral augmentation. Despite potential
      adverse effects, medical management, including nonsteroidal anti-inflammatory
      drugs, calcitonin, teriparatide, and bisphosphonates, remains the first-line
      therapy for patients. Evidence suggests that vertebral augmentation, especially
      some of the newer procedures, have the potential to dramatically reduce pain and
      improve quality of life. At this time, balloon-assisted kyphoplasty is the
      procedure with the most evidence of support. CONCLUSIONS: Based on current
      literature, it is evident that there is a lack of standard of care for patients
      with vertebral compression fractures, which is either due to lack of evidence
      that a procedure is successful or due to serious adverse effects encountered with
      prolonged treatment. For a consensus to be reached, prospective clinical trials
      need to be formulated with potential new biomarkers to assess efficacy of
      treatment strategies.

PMID- 28451513
TI  - Differences between Manufacturers of Computed Tomography-Based Computer-Assisted
      Surgery Systems Do Exist: A Systematic Literature Review.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: Several studies have shown that the
      accuracy of pedicle screw placement significantly improves with use of computed
      tomography (CT)-based navigation systems. Yet, there has been no systematic
      review directly comparing accuracy of pedicle screw placement between different
      CT-based navigation systems. The objective of this study is to review the results
      presented in the literature and compare CT-based navigation systems relative only
      to screw placement accuracy. METHODS: Data sources included CENTRAL, Medline,
      PubMed, and Embase databases. Studies included were randomized clinical trials,
      case series, and case-control trials reporting the accuracy of pedicle screws
      placement using CT-based navigation. Two independent reviewers extracted the data
      from the selected studies that met our inclusion criteria. Publications were
      grouped based on the CT-based navigation system used for pedicle screw placement.
      RESULTS: Of the 997 articles we screened, only 26 met all of our inclusion
      criteria and were included in the final analysis, which showed a significant
      statistical difference (p < 0.0001, 95% confidence interval 0.92 to 1.23) in
      accuracy of pedicle screw placement between three different CT-based navigation
      systems. The mean (weighted) accuracy of pedicle screws placement based on the CT
      based navigation system was found to be 97.20 +/- 2.1% in StealthStation
      (Medtronic, United States) and 96.1 +/- 3.9% in VectorVision (BrainLab, Germany).
      CONCLUSION: This review summarizes results presented in the literature and
      compares screw placement accuracy using different CT-based navigation systems.
      Although certain factors such as the extent of the procedure and the experience
      and skills of the surgeon were not accounted for, the differences in accuracy
      demonstrated should be considered by spine surgeons and should be validated for
      effects on patients' outcome.

PMID- 28451514
TI  - Dysphagia Rates after Anterior Cervical Diskectomy and Fusion: A Systematic
      Review and Meta-Analysis.
AB  - STUDY DESIGN:  Systematic review and meta-analysis. OBJECTIVE: Anterior cervical
      diskectomy and fusion (ACDF) is an effective surgical option for patients with
      cervical radiculopathy, myelopathy, or deformity. Although ACDF is generally
      safe, dysphagia is a common complication. Despite its high incidence, prolonged
      postoperative dysphagia is poorly understood; its etiology remains relatively
      unknown, and its risk factors are widely debated. METHODS: We searched MEDLINE,
      Scopus, Web of Science, and Embase for studies reporting complications for
      cervical diskectomy with plating. We recorded dysphagia events from all included
      studies and calculated effect summary values, 95% confidence intervals (CIs), Q
      values, and I2 values. RESULTS: Of the 7,780 retrieved articles, 14 met inclusion
      criteria. The overall dysphagia rate was 8.5% (95% CI 5.7 to 11.3%). The rate of
      moderate or severe dysphagia was 4.4% (0.4 to 8.4%). Follow-up times of <12, 12
      to 24, and >24 months reported rates of 19.9% (6.0 to 33.7%), 7.0% (5.2 to 8.7%),
      and 7.6% (1.4 to 13.8%), respectively. Studies utilizing the Bazaz Dysphagia
      Score resulted in an increase in dysphagia diagnosis relative to studies with no
      outlined criteria (19.8%, 5.9 to 33.7% and 6.9%, 3.7 to 10.0%, respectively),
      indicating that the criteria used for dysphagia identification are critical.
      There was no difference in dysphagia rate with the use of autograft versus
      allograft. CONCLUSIONS: This review represents a comprehensive estimation of the
      actual incidence of dysphagia across a heterogeneous group of surgeons, patients,
      and criteria. The classification scheme for dysphagia varied significantly within
      the literature. To ensure its diagnosis and identification, we recommend the use
      of a standardized, well-outlined method for dysphagia diagnosis.

PMID- 28451515
TI  - Islet cell transplant: Update on current clinical trials.
AB  - In the last 15 years clinical islet transplantation has made the leap from
      experimental procedure to standard of care for a highly selective group of
      patients. Due to a risk-benefit calculation involving the required systemic
      immunosuppression the procedure is only considered in patients with type 1
      diabetes, complicated by severe hypoglycemia or end stage renal disease. In this
      review we summarize current outcomes of the procedure and take a look at ongoing
      and future improvements and refinements of beta cell therapy.

PMID- 28451517
TI  - UV-C inactivation of Legionella rubrilucens.
AB  - Background: Despite the great health significance of Legionella, there is only
      little information on their UV sensitivity. Besides Legionella pneumophila only
      L. longbeachae has been investigated so far. Methods: In this study L.
      rubrilucens has been spread on buffered charcoal yeast extract agar and
      irradiated with the 254 nm UV-C emission of a mercury vapor lamp. The
      disinfection success is measured by colony counting after incubation and
      comparison of the number of colonies on irradiated and unirradiated reference
      agar plates. Results: The average log-reduction dose is 1.08 mJ/cm2 for free L.
      rubrilucens, which is at the lower end of the so far published Legionella log
      reduction values, but all three Legionella species show similar UV-C
      sensitivities. Conclusion: The log-reduction dose of legionellae in amoebae has
      not been investigated, but with the observed high UV-C sensitivity for free
      Legionella, the idea of a future point-of-use disinfection by small UV-C LEDs in
      water-taps or shower heads appears to be realistic, even if legionellae are more
      resistant in amoebae.

PMID- 28451518
TI  - Development and application of the RE-AIM QuEST mixed methods framework for
      program evaluation.
AB  - To increase the likelihood of successful implementation of interventions and
      promote dissemination across real-world settings, it is essential to evaluate
      outcomes related to dimensions other than Effectiveness alone. Glasgow and
      colleagues' RE-AIM framework specifies four additional types of outcomes that are
      important to decision-makers: Reach, Adoption, Implementation (including cost),
      and Maintenance. To further strengthen RE-AIM, we propose integrating qualitative
      assessments in an expanded framework: RE-AIM Qualitative Evaluation for
      Systematic Translation (RE-AIM QuEST), a mixed methods framework. RE-AIM QuEST
      guides formative evaluation to identify real-time implementation barriers and
      explain how implementation context may influence translation to additional
      settings. RE-AIM QuEST was used to evaluate a pharmacist-led hypertension
      management intervention at 3 VA facilities in 2008-2009. We systematically
      reviewed each of the five RE-AIM dimensions and created open-ended companion
      questions to quantitative measures and identified qualitative and quantitative
      data sources, measures, and analyses. To illustrate use of the RE-AIM QuEST
      framework, we provide examples of real-time, coordinated use of quantitative
      process measures and qualitative methods to identify site-specific issues, and
      retrospective use of these data sources and analyses to understand variation
      across sites and explain outcomes. For example, in the Reach dimension, we
      conducted real-time measurement of enrollment across sites and used qualitative
      data to better understand and address barriers at a low-enrollment site. The RE
      AIM QuEST framework may be a useful tool for improving interventions in real
      time, for understanding retrospectively why an intervention did or did not work,
      and for enhancing its sustainability and translation to other settings.

PMID- 28451516
TI  - Antibiotic resistance: What is so special about multidrug-resistant Gram-negative
      bacteria?
AB  - In the past years infections caused by multidrug-resistant Gram-negative bacteria
      have dramatically increased in all parts of the world. This consensus paper is
      based on presentations, subsequent discussions and an appraisal of current
      literature by a panel of international experts invited by the Rudolf Schulke
      Stiftung, Hamburg. It deals with the epidemiology and the inherent properties of
      Gram-negative bacteria, elucidating the patterns of the spread of antibiotic
      resistance, highlighting reservoirs as well as transmission pathways and risk
      factors for infection, mortality, treatment and prevention options as well as the
      consequences of their prevalence in livestock. Following a global, One Health
      approach and based on the evaluation of the existing knowledge about these
      pathogens, this paper gives recommendations for prevention and infection control
      measures as well as proposals for various target groups to tackle the threats
      posed by Gram-negative bacteria and prevent the spread and emergence of new
      antibiotic resistances.

PMID- 28451519
TI  - A longitudinal ecological study of household firearm ownership and firearm
      related deaths in the United States from 1999 through 2014: A specific focus on
      gender, race, and geographic variables.
AB  - Firearms have a longstanding tradition in the United States (US) and are viewed
      by many with iconic stature with regards to safety and personal freedom.
      Unfortunately, from a public health point of view, firearm-related deaths (FRDs)
      in the US have reached a crisis point with an estimated > 31,000 deaths and
      74,000 nonfatal injuries resulting from firearms each year. This longitudinal
      ecological study analyzed variations in FRDs following firearm assaults (FAs) and
      law enforcement incidents involving a firearm (LEIF) in comparison to variations
      in household firearm ownership (HFO) among different geographic and demographic
      groups in the US from 1999 to 2014. The Underlying Cause of Death database was
      examined on the CDC Wonder online interface. Records coded with ICD-10 codes: FA
      (X93 - assault by handgun discharge, X94 - assault by rifle, shotgun, and larger
      firearm discharge, or X95 - assault by other and unspecified firearm discharge)
      and LEIF (Y35.0) were examined, and the prevalence of HFO was determined using
      the well-established proxy of the percentage of suicides committed with a
      firearm. Gender, ethnicity, Census Division, and urbanization significantly
      impacted the death rates from FA and LEIF. Significant direct correlations
      between variations in HFO and death rates from FAs and LEIF were observed.
      Understanding the significant impacts of gender, race, Census Division, and
      urbanization status may help shape future public health policy to promote
      increased firearm safety.

PMID- 28451520
TI  - Three-Dimensional, computer simulated navigation in endoscopic neurosurgery.
AB  - BACKGROUND: In order to address the pre- and perioperative need for visualization
      and prediction of patient-specific anatomy for surgical planning, endoscopic
      neurosurgeons have increasingly relied on computerized navigation devices to
      guide their surgical approaches. OBJECTIVE: This manuscript aims to review: 1)
      the use of neuronavigation in endoscopic neurosurgery for pre-operative planning,
      2) the intraoperative advantages of neuronavigation in endoscopic neurosurgery,
      and 3) the effects of navigation guidance on operative time, registration
      accuracy, brain shift, and avoidance of complications. Limitations of the current
      neuroendoscopic navigation literature will be discussed. METHODS: We conducted a
      search using PubMed-MEDLINE; the keywords "stereotactic navigation AND endoscopic
      surgery" and "simulation AND endoscopic neurosurgery". 36 studies were identified
      that addressed the use of neuronavigation in endoscopic neurosurgery. These
      studies were then further analyzed for topics relevant to computerized
      neuroendoscopy and reviewed for the purposes of this article. CONCLUSION: Three
      dimensional, frameless neuronavigation systems are useful in endoscopic
      neurosurgery to assist in the pre-operative planning of potential trajectories
      and to help localize the pathology of interest. Neuronavigation appears to be
      accurate to < 1-2 mm without issues related to brain shift. Further work is
      necessary in the investigation of the effect of neuronavigation on operative
      time, cost, and patient-centered outcomes.

PMID- 28451523
TI  - Life Style and Sustainable Development.

PMID- 28451521
TI  - T3SS-Independent Uptake of the Short-Trip Toxin-Related Recombinant NleC Effector
      of Enteropathogenic Escherichia coli Leads to NF-kappaB p65 Cleavage.
AB  - Effector proteins secreted by the type 3 secretion system (T3SS) of pathogenic
      bacteria have been shown to precisely modulate important signaling cascades of
      the host for the benefit of the pathogens. Among others, the non-LEE encoded T3SS
      effector protein NleC of enteropathogenic Escherichia coli (EPEC) is a Zn
      dependent metalloprotease and suppresses innate immune responses by directly
      targeting the NF-kappaB signaling pathway. Many pathogenic bacteria release
      potent bacterial toxins of the A-B type, which-in contrast to the direct
      cytoplasmic injection of T3SS effector proteins-are released first into the
      environment. In this study, we found that NleC displays characteristics of
      bacterial A-B toxins, when applied to eukaryotic cells as a recombinant protein.
      Although lacking a B subunit, that typically mediates the uptake of toxins,
      recombinant NleC (rNleC) induces endocytosis via lipid rafts and follows the
      endosomal-lysosomal pathway. The conformation of rNleC is altered by low pH to
      facilitate its escape from acidified endosomes. This is reminiscent of the
      homologous A-B toxin AIP56 of the fish pathogen Photobacterium damselae piscicida
      (Phdp). The recombinant protease NleC is functional inside eukaryotic cells and
      cleaves p65 of the NF-kappaB pathway. Here, we describe the endocytic uptake
      mechanism of rNleC, characterize its intracellular trafficking and demonstrate
      that its specific activity of cleaving p65 requires activation of host cells
      e.g., by IL1beta. Further, we propose an evolutionary link between some T3SS
      effector proteins and bacterial toxins from apparently unrelated bacteria. In
      summary, these properties might suggest rNleC as an interesting candidate for
      future applications as a potential therapeutic against immune disorders.

PMID- 28451524
TI  - Fat Mass and Obesity Associated Gene Polymorphism and the Risk of Polycystic
      Ovary Syndrome: A Meta-analysis.
AB  - BACKGROUND: We aimed to elucidate the association between fat mass and obesity
      associated gene (FTO) polymorphism and the risk of polycystic ovary syndrome
      (PCOS) by meta-analysis. METHODS: We searched PubMed and Embase databases to find
      the relevant studies. Odds ratios (ORs) and their corresponding 95% confidence
      intervals (CIs) were used for pooled analysis. Statistical analyses were carried
      out by using R 3.12 software. Heterogeneity was assessed using I 2 and Q
      statistics. I 2 >50% or P<0.05 was considered as heterogeneity statistically, and
      random effects model was used for pooled analysis. Otherwise, fixed-effect model
      was used. RESULTS: Twelve eligible studies that published from 2008 to 2015 were
      included in this meta-analysis. The pooled analyses showed that rs9939609
      polymorphism of FTO gene was significantly associated with risk of PCOS under A
      vs. T, AT vs. TT, AA vs. TT, AA vs. AT+TT and AA+AT vs. TT genetic models.
      However, for rs8050136 and rs1421085, significant association was only found
      under recessive genetic model. CONCLUSION: rs9939609 variation of FTO gene is
      significantly associated with risk of PCOS. However, the association between
      rs8050136, rs1421085, and PCOS is still unclear and needs further confirmation.

PMID- 28451522
TI  - Ureaplasma Species Multiple Banded Antigen (MBA) Variation Is Associated with the
      Severity of Inflammation In vivo and In vitro in Human Placentae.
AB  - Background: The multiple banded antigen (MBA), a surface-exposed lipoprotein, is
      a proposed virulence factor of Ureaplasma spp. We previously demonstrated that
      the number of Ureaplasma parvum MBA size variants in amniotic fluid was inversely
      proportional to the severity of chorioamnionitis in experimentally infected
      pregnant sheep. However, the effect of ureaplasma MBA size variation on
      inflammation in human pregnancies has not been reported. Methods: Ureaplasmas
      isolated from the chorioamnion of pregnant women from a previous study (n = 42)
      were speciated/serotyped and MBA size variation was demonstrated by PCR and
      western blot. Results were correlated with the severity of chorioamnionitis and
      cord blood cytokines. In vitro, THP-1-derived macrophages were exposed to
      recombinant-MBA proteins of differing sizes and NF-kappaB activation and cytokine
      responses were determined. Results: MBA size variation was identified in 21/32
      (65.6%) clinical isolates (in 10 clinical isolates MBA size variation was unable
      to be determined). Any size variation (increase/decrease) of the MBA (regardless
      of Ureaplasma species or serovar) was associated with mild or absent
      chorioamnionitis (P = 0.023) and lower concentrations of cord blood cytokines IL
      8 (P = 0.04) and G-CSF (P = 0.008). In vitro, recombinant-MBA variants elicited
      different cytokine responses and altered expression of NF-kappaB p65. Conclusion:
      This study demonstrates that size variation of the ureaplasma MBA protein
      modulates the host immune response in vivo and in vitro.

PMID- 28451525
TI  - Quality of Life among General Populations of Different Countries in the Past 10
      Years, with a Focus on Human Development Index: A Systematic Review and Meta
      analysis.
AB  - BACKGROUND: The current study was conducted to estimate the integrated mean of
      Quality Of Life (QOL) of the general population of different countries around the
      world and to compare them on the grounds of the Human Development Index (HDI).
      METHODS: Well-known international databases such as Medline, Scopus, Science
      Direct, Google Scholar & Google, and domestic databases including SID, IranMedex,
      Irandoc & Magiran were searched in 2015. The data were analyzed with the Random
      Effect Model, using Stata 11 software. RESULTS: Ninety-seven studies were
      selected for the final analysis. The overall QOL mean in the very high HDI
      subgroup was 74.26 (CI=72.40-76.12), which was the highest value. The lowest mean
      score was observed in the psychological domain (M=67.37; CI=66.23-68.52). In the
      high HDI subgroup, the highest mean was observed in the social relationships
      domain (M=64.16; CI=61.99-66.34), and the lowest mean was observed in the
      environment domain (M=58.76; CI=56.50-61.03). In the medium HDI subgroup, the
      highest mean was calculated for the overall QOL score (M=62.62; CI=56.35-68.92),
      and the lowest mean was estimated for the environment domain (M=56.98; CI=53.54
      60.43). The highest mean in the low HDI subgroup was observed in the physical
      health domain (M=68.17; CI=67.43-70.52), and the lowest mean was calculated for
      the environment domain (M=53.14; CI=51.57-54.72). There was considerable
      heterogeneity in all the subgroups and domains; the values reported here are the
      weighted means of QOL for different countries. CONCLUSION: Overall, the highest
      means of various QOL domains were observed in the very high HDI subgroup.

PMID- 28451526
TI  - Vitamin C and Vitamin E Protected B95-8 and Balb/c-3T3 Cells from Apoptosis
      Induced by Intermittent 50Hz ELF-EMF Radiation.
AB  - BACKGROUND: The extremely low-frequency electromagnetic field (ELF-EMF), mainly
      emitted by electric transmission lines and household electronic appliances, is
      becoming a worldwide health risk. It is imperative to investigate the biological
      impacts of ELF-EMF and to identify products that are resistant to the radiation
      from 50 Hz ELF-EMF. In this study, we investigated the biological impacts of
      apoptosis caused by 50 Hz Power line ELF-EMF and the protective effects of Vit C
      and Vit E. METHODS: We conducted this study in Beijing, China in 2013. B95-8 and
      Balb/c-3T3 cells were divided into a sham group, an expo group and 3 expo groups
      in which the cells were preincubated with various concentrations of Vit C and Vit
      E. Then, all of the cells were exposed to 50 Hz Power line ELF-EMF and examined
      for apoptosis. The cells were collected for apoptosis detection after exposure.
      RESULTS: The percent of cells that undergoing apoptosis and preincubated with
      various concentrations of Vit C and Vit E were significantly lower than in the
      Expo group. CONCLUSION: Vit C and Vit E exert significant protective effects from
      50 Hz ELF-EMF radiation. The optimal protective concentrations of Vit C and Vit E
      are 10 MUmol/L and 25 MUmol/L, respectively. The protective effect of vitamins
      was more apparent for Balb/c-3T3 cells than B95-8 cells.

PMID- 28451527
TI  - Model-based Recursive Partitioning for Survival of Iranian Female Breast Cancer
      Patients: Comparing with Parametric Survival Models.
AB  - BACKGROUND: Precise diagnosis of disease risk factors via efficient statistical
      models is the primary step for reducing the heavy costs of breast cancer, as one
      of the most highly prevalent cancer throughout the world. Therefore, the aim of
      this study was to present a recently introduced statistical model in order to
      assess its proficiency for model fitting. METHODS: The information of 1465
      eligible Iranian women with breast cancer was used for this retrospective cohort
      study. The statistical performances of exponential, Weibull, Log-logistic and
      Lognormal, as the most proper parametric survival models, were evaluated and
      compared with 'Model-based Recursive Partitioning' in order to survey their
      capability of more relevant risk factor detection. RESULTS: 'Model-based
      Recursive Partitioning' recognized the largest number of significant affective
      risk factors, whereas, all four parametric models agreed and unable to detect the
      effectiveness of 'Progesterone Receptor' as an indicator; 'Log-Normal-based
      Recursive Partitioning' could provide the paramount fit. CONCLUSION: The
      superiority of 'Model-based Recursive Partitioning' was ascertained; not only by
      its excellent fitness but also by its susceptibility for classification of
      individuals to homogeneous severity levels and its impressive visual intuition
      potentiality.

PMID- 28451528
TI  - Analysis of Factors Influencing the Grading of Condition Severity and Zoning
      Management in an Emergency Triage System.
AB  - BACKGROUND: To identify and analyze factors that influence the grading and zoning
      management model of emergency triage as a first step in the improvement of the
      system. METHODS: Questionnaires were used to extract data from clinical histories
      of 286 patients who attended the Emergency Department of Binzhou Central Hospital
      (Binzhou City, Shandong Province, China) from September to November of 2015.
      Through logistic regression analysis, influencing factors for unreasonable (>=
      2h) emergency department retention times were identified. RESULTS: Analysis of
      general characteristics of patients including gender, method of payment or
      assigned medical department did not result in any statistically significant
      differences between patients with a time to discharge longer than 2 h and those
      with a shorter time to discharge (P > 0.05). Older age, higher income, lower or
      higher education degree, admission time from 17:00-7:59, and lack of
      understanding of zoning management and of condition severity grading resulted in
      a retention time greater than or equal to 2 hours (P < 0.05). According to the
      Logistic regression model: age, income level, education degree, admission time,
      degree of understanding of zoning management and condition severity grading were
      all independent risk factors affecting the time to discharge from the emergency
      department (P <0.05). CONCLUSION: Countermeasures need to be developed in order
      to minimize the influence of patients' factors and promote reasonable average
      retention times lower than 2 hours in the emergency department.

PMID- 28451529
TI  - Efficacy of Emotion Regulation for Patients Suffering from Chronic Obstructive
      Pulmonary Disease.
AB  - BACKGROUND: To study the influence values of self-management program intervention
      on efficacy of emotion regulation for patients suffering from chronic obstructive
      pulmonary disease (COPD). METHODS: Eighty-six diagnosed chronic COPD patients in
      stable phase in Linzi District People's Hospital, Zibo Shandong Province, PR
      China from June 2014 to June 2015 were selected in succession. They were divided
      into control group and observation group randomly with 43 cases in each group. In
      control group, conventional out-of-hospital continued nursing mode was used while
      strengthened self-management program guidance was used in observation group
      (including seven modules that included disease knowledge, breathing exercises,
      emotion management, home oxygen therapy, medicine intake technique, healthy life
      behaviors, and action plans in deterioration stage) to compare their differences
      of results. RESULTS: For follow-up visits of 6 months, self-management behaviors
      of patients in two groups had increased, including physical fitness training,
      cognitive symptom management practice and medical care scores, and the increase
      range in observation group was more obvious and differences were of statistical
      significance (P < 0.05); self-efficacy of emotion regulation in two groups is
      increasing, including positive affect, despondency/distress, anger/irritation and
      total scores, furthermore, the increase range in observation group is more
      obvious and differences are of statistical significance (P < 0.05). CONCLUSION:
      Self-management program intervention can improve self-management behaviors of
      COPD patients and it is significant in terms of improving efficacy of emotion
      regulation and prognosis.

PMID- 28451530
TI  - Impact of Diabetic Retinopathy on Health-related Quality of Life in Iranian
      Diabetics.
AB  - BACKGROUND: To extract utility values of diabetic retinopathy on a perfect health
      and perfect vision scales for Iranians with both types diabetes. METHODS: In this
      investigation, 150 untreated patients with diabetic retinopathy consecutively
      were examined and interviewed in Farabi Eye Hospital, Tehran, Iran, a tertiary
      referral center in the Iranian health care system. Utility values based on
      patients-reported outcome measures, standard gamble, time trade off and visual
      analogue scale approaches, were estimated. RESULTS: Considering all three utility
      elicitation methods were valid, diabetic retinopathy patients, on average
      reported the 0.95 (+/-0.03), 0.85 (+/-0.15) and 0.80 (+/-0.30) standard policy
      scale utility according to standard gamble, TTO and VAT respectively. In all
      three-studied approach, diabetic retinopathy had more disutility in higher levels
      of disease and had more disutility in the presence of both maculopathy and
      vasculopathy compared with one of them. Evidence show that share of macular edema
      in imposing disutility was maximum in early stage and exponentially decreased
      with advancing the severity of diabetic retinopathy. CONCLUSION: Study indicated
      utility scores in DR-experienced Iranian patients were highest with the SG and
      lowest with the VAT method. The proffered utility-elicitation method in Iranian
      patient populations could be the TTO approach. The novel model we employed for DR
      takes the effects of diabetic macular edema and vascularization into account
      separately, and can provide a better estimate of the QoL for these patients.

PMID- 28451531
TI  - Family Planning Practice by Patterns of Marriage in the North of Iran.
AB  - BACKGROUND: The fertility experience in Iran suggests that the family planning
      programs had an effective role in the fertility reduction. This study aimed to
      specify patterns of marriage in Iran and especially in a northern city of Iran
      and to investigate the association between patterns of marriage and contraceptive
      use before first pregnancy and current contraceptive use. METHODS: In this cross
      sectional study, following the implementation of an expert panel in order to
      investigate marriage patterns, 880 women aged 15-49 yr old, were selected by
      multistage cluster sampling and completed the "reproductive practices"
      questionnaire in Babol City, northern Iran, in 2013. The data were analyzed using
      IBM SPSS ver.16 and descriptive and analytical parameters. RESULTS: There are
      three patterns of marriage in the northern part of Iran: Traditional, Mixed and
      Modern marriage and between different patterns there is no statistically
      significant difference in the contraceptive use. CONCLUSION: According to the
      lack of significant relationship between patterns of marriage and the
      contraceptives use, which is one of the proximate determinants of fertility, the
      policy makers should pay attention to other determinants of fertility in order to
      manage the problems and implications of population decline in the country.

PMID- 28451532
TI  - Screening of Myo7A Mutations in Iranian Patients with Autosomal Recessive Hearing
      Loss from West of Iran.
AB  - BACKGROUND: Hearing loss (HL) is the most frequent neurosensory impairment. HL is
      highly heterogeneous defect. This disorder affects 1 out of 500 newborns. This
      study aimed to determine the role of DFNB2 locus and frequency of MYO7A gene
      mutations in a population from west of Iran. METHODS: Thirty families
      investigated in Shahrekord University of Medical Sciences in 2014, genetic
      linkage analysis via four short tandem repeat markers linked to MYO7A was
      performed for two consanguineous families originating from Hamedan (family-13)
      and Chaharmahal-Bakhtiari (family-32) provinces of Iran, co-segregating autosomal
      recessive HL and showed no mutation in GJB2 gene in our preliminary
      investigation. All 49 coding exons and exon- intron boundaries of the MYO7A gene
      were amplified by PCR and analyzed using direct DNA sequencing. RESULTS: Two of
      families displayed linkage to DFNB2. Family-13 segregated a homozygous missense
      mutation (c.6487G>A) in exon 48 that results in a p.G2163S amino acid
      substitution in C-terminal domain of the myosin VIIA protein. While family-32
      segregated a homozygous nonsense mutation (c.448 C>T) in exon five, resulting in
      a premature truncation at amino acid position 150 (p.Arg150X) in the motor domain
      of this protein. CONCLUSION: Mutation frequency of MYO7A gene in different
      populations of Iran as well as cause of HL in most cases are still unknown and
      more extensive studies have to be done.

PMID- 28451533
TI  - Application of Multivariate Statistical Methods to Optimize Water Quality
      Monitoring Network with Emphasis on the Pollution Caused by Fish Farms.
AB  - BACKGROUND: One of the key issues in determining the quality of water in rivers
      is to create a water quality control network with a suitable performance. The
      measured qualitative variables at stations should be representative of all the
      changes in water quality in water systems. Since the increase in water quality
      monitoring stations increases annual monitoring costs, recognition of the
      stations with higher importance as well as main parameters can be effective in
      future decisions to improve the existing monitoring network. METHODS: Sampling
      was carried out on 12 physical and chemical parameters measured at 15 stations
      during 2013-2014 in Haraz River, northern Iran. RESULTS: The results of the
      measurements were analyzed using multivariate statistical analysis methods
      including cluster analysis (CA), principal component analysis (PCA), factor
      analysis (FA), and discriminant analysis (DA). According to the CA, PCA, and FA,
      the stations were divided into three groups of high pollution, medium pollution,
      and low pollution. CONCLUSION: The research findings confirm applicability of
      multivariate statistical techniques in the interpretation of large data sets,
      water quality assessment, and source apportionment of different pollution
      sources.

PMID- 28451534
TI  - Determination the Levels of Subjective and Observer Rating of Drowsiness and
      Their Associations with Facial Dynamic Changes.
AB  - BACKGROUND: We determined the levels of subjective and observer drowsiness and
      facial dynamics changes. METHODS: This experimental study was done in the virtual
      reality laboratory of Khaje-Nasir Toosi University of Technology in 2015. Facial
      dynamics changes like changes in eyes, mouth and eyebrows were surveyed on twenty
      five drivers in 2015byKSS (Karolinska Sleepiness Scale) and ORD (Observer Rating
      of Drowsiness). ANOVA Repeated Measure and MANOVA Repeated Measure tests were
      used for data analysis. Also, neural network and Viola-Jones were used to detect
      facial characteristics. PERCLOS (Percentage of Eye Closure), blink frequency and
      blink duration were inspected for eyes parameters. The size of open mouth during
      drowsiness was inspected for mouth parameter. During the inspection of eyebrow,
      the number 50 denoted eyebrow in normal position. For eyebrows above the normal
      position, a range of 50 to 55 was specified; in addition, 45-50 was found as the
      specified range for eyebrows under normal position. RESULTS: Descriptive
      statistics of the dynamic changes in mouth and eyes illustrated that during the
      driving process, the level of sleepiness increased as well as changes of eyes and
      mouth. However, statistical findings during car driving revealed that dynamic
      changes in eyebrows had clear expression with a constant trend. Similar studies
      on data obtained from KSS and ORD showed that both of these parameters
      simultaneously increased as well as the level of drowsiness. In addition, a
      significant relationship existed between facial expression and drowsiness.
      CONCLUSION: This research would be an effective and efficient tool for timely
      alarming and detecting the drowsiness quickly and precisely.

PMID- 28451535
TI  - Simultaneous Molecular Detection of Salmonella enterica Serovars Typhi,
      Enteritidis, Infantis, and Typhimurium.
AB  - BACKGROUND: Salmonella enterica serovar Typhi, as causative agent of typhoid
      fever, is one of the most important endemic pathogens. Non-typhoidal Salmonella
      serovars, including Typhimurium, Infantis, and Enteritidis are amongst the most
      prevalent serotypes worldwide and in developing areas such as Iran. The aim of
      this study was to apply a uniplex PCR for rapid detection of Salmonella spp., and
      a multiplex PCR for the simultaneous detection of the four most common Salmonella
      serovars in Iran. METHODS: Current research was done in 2010 at Molecular Biology
      Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. For
      detection of Salmonella spp a pair of primers was used to replicate a chromosomal
      sequence. Four other sets of primers were also designed to amplify the target
      genes of four Salmonella species including S. typhi, and three non-typhoidal
      Salmonella spp (S. enteritidis, S. infantis, and S. typhimurium). The assay
      specificity was investigated by testing 15 different Salmonella serovars and 8
      other additional non-Salmonella species. RESULTS: The Salmonella genus-specific
      PCR yielded the expected DNA band of 404 bp in all Salmonella spp., strains
      tested. The uniplex and multiplex PCR assays produced also the expected fragments
      of 489 bp, 304 bp, 224 bp, and 104 bp for serovars Typhi, Enteritidis,
      Typhimurium, and Infantis, respectively. Each species-specific primer pair set
      did not show any cross-reactivity when tested on other Salmonella serovars or
      other non- but related- Salmonella strains. CONCLUSION: Both uniplex and
      multiplex PCR protocols had a good specificity. They can provide an important
      tool for the rapid and simultaneous detection and differentiation of the four
      most prevalent Salmonella serovars in Iran.

PMID- 28451536
TI  - Neonatal Screening: Cost-utility Analysis for Galactosemia.
AB  - BACKGROUND: Galactosemia is a congenital metabolic disorder that can damage the
      health of a newborn. Screening is an important step to prevent and treat this
      condition. Due to increasing health care costs and limited financial resources of
      health systems, the most suitable economic analysis tool should be applied. The
      aim of this study was to analyze the cost-utility of neonatal screening program
      for diagnosing galactosemia in Fars province, Iran. METHODS: In this cross
      sectional study and cost-utility analysis in the cost of screening for
      galactosemia and its financial effects, decision tree model and society's
      viewpoint were used. The population of study was 81837 infants referred to
      Neonatal Screening Laboratory (Nader Kazemi Clinic) affiliated to Shiraz
      University of Medical Sciences (SUMS), Iran, in 2010. Quality of life in two
      groups of patients was evaluated by using the time trade-off. The best
      intervention option was selected by using the Incremental Cost-effectiveness
      Ratio. RESULTS: The estimated cost of diagnosed through screening and without
      screening were 43519911 and 130011168 Iranian Rails (4222.00 $ and 12615.00 $),
      respectively. Therefore, there was a saving of 201443240.99 Iranian Rails
      (19641.00 $), for each patient annually. CONCLUSION: The screening program can
      improve both the qualitative and quantitative lifestyle of people and increase
      savings in health care system. Policymakers could use the results to design new
      policies based on the necessity of screening.

PMID- 28451537
TI  - Using Routine Data to Categorize Poor Control Diabetic Patients: An Application
      of Cluster Analysis Technique.
AB  - BACKGROUND: Diabetes mellitus is one of the most important causes of morbidity
      and mortality all over the world. Chronic high blood glucose is the root cause of
      developing future micro and macro vascular complications. In current study, we
      analyzed poorly controlled patients' information by clustering method in order to
      find more homogenous sub-groups of patients for planning for further
      interventions. METHODS: This study was conducted based on medical records of
      diabetic patients admitted to 23 health care centers in four cities of Iran from
      2010 to 2014. Demographic data and physical and biochemical measurements were
      extracted and analyzed using two-steps cluster analysis method. RESULTS: Three
      distinct clusters were derived from 2087 eligible cases. Cluster 1 totally
      consisted of men without any apparent risk factors. Members of clusters 2 and 3
      were illiterate women with obesity. Dyslipidemia was a prominent characteristic
      in members of cluster 2. CONCLUSION: Masculinity would play the main role in
      diabetes control. Meanwhile, aggregation of obesity, illiteracy and/or
      dyslipidemia in diabetic women predispose them to poor control condition. Based
      on these findings, we will be able to plan interventions that are more
      appropriate for identified groups.

PMID- 28451538
TI  - Plasma Membrane Redox System in the Erythrocytes of Rowers: Pilot Study.

PMID- 28451539
TI  - Tuberculosis Incidence and Its Predictive Factors among Patients Receiving
      Antiretroviral Therapy in Dilla Hospital, Ethiopia.

PMID- 28451540
TI  - Determination of Drug Compliance of Hypertensive Individuals.

PMID- 28451541
TI  - Applying Hot Compresses with Rhubarb and Mirabilite to Reduce Pancreatic Leakage
      Occurrence in the Treatment of Severe Acute Pancreatitis.

PMID- 28451542
TI  - Complications of Acute Coronary Syndrome in Young Patients.

PMID- 28451543
TI  - Application of Cognitive-behavioural Techniques on Changes in the Scope of
      Dieting Self-efficacy Level among Obese People.

PMID- 28451544
TI  - Life Skills Needs Assessment among Iranian Immigrant Students in Malaysia.

PMID- 28451545
TI  - Severe Acro-osteolysis in a Case of Limited Cutaneous Scleroderma.

PMID- 28451546
TI  - Pervasive Decision Support Systems in Healthcare Using Intelligent Robots in
      Social Media.

PMID- 28451547
TI  - Perception of Paralytic Ileus on Viewpoint of Avicenna.

PMID- 28451548
TI  - Analysis of Papers Submitted to "Iranian Journal of Public Health" during 2013
      2016.

PMID- 28451549
TI  - Implications of Dual Practice among Health Workers: A Systematic Review.
AB  - BACKGROUND: Mixed health care systems to work simultaneously on both public and
      private facilities, is common today. This phenomenon referred to as dual practice
      (DP), has potential implications for access, quality, cost and equity of health
      services. This paper aimed to review systematically studies that assess the
      implications of DP among health workers. METHODS: MEDLINE, EMBASE, and The
      Cochrane library were searched for obtaining published literature between Feb
      1990 and May 2014. Google and Google Scholars, organizational websites, and
      reference lists of relevant papers searched to get grey literature. Only studies
      concentrated on consequences and impacts of DP among health professionals and
      conducted using "randomized controlled trials", "non-randomized controlled
      trials", "controlled before and after studies", or "interrupted time series" were
      eligible for inclusion. RESULTS: From 3242 records, we focused on 19 studies,
      which aimed to assess effects and impacts of dual practice. After that, the
      current understanding of DP positive and negative implications was categorized
      and discussed based on two perspectives. CONCLUSION: There has been a propensity
      to over-reliance on theoretical methods in predicting the implications of this
      phenomenon. Almost all of the mentioned implications are based on theoretical
      predictions undermined in the broader literature. Furthermore, assessing the
      current literature showed positive and negative impacts of DP on different parts
      of the health system and various dimensions of service delivery. These
      implications are contexted specific and may vary from system to system.

PMID- 28451550
TI  - Improving the Prediction of Survival in Cancer Patients by Using Machine Learning
      Techniques: Experience of Gene Expression Data: A Narrative Review.
AB  - BACKGROUND: Today, despite the many advances in early detection of diseases,
      cancer patients have a poor prognosis and the survival rates in them are low.
      Recently, microarray technologies have been used for gathering thousands data
      about the gene expression level of cancer cells. These types of data are the main
      indicators in survival prediction of cancer. This study highlights the
      improvement of survival prediction based on gene expression data by using machine
      learning techniques in cancer patients. METHODS: This review article was
      conducted by searching articles between 2000 to 2016 in scientific databases and
      e-Journals. We used keywords such as machine learning, gene expression data,
      survival and cancer. RESULTS: Studies have shown the high accuracy and
      effectiveness of gene expression data in comparison with clinical data in
      survival prediction. Because of bewildering and high volume of such data, studies
      have highlighted the importance of machine learning algorithms such as Artificial
      Neural Networks (ANN) to find out the distinctive signatures of gene expression
      in cancer patients. These algorithms improve the efficiency of probing and
      analyzing gene expression in cancer profiles for survival prediction of cancer.
      CONCLUSION: By attention to the capabilities of machine learning techniques in
      proteomics and genomics applications, developing clinical decision support
      systems based on these methods for analyzing gene expression data can prevent
      potential errors in survival estimation, provide appropriate and individualized
      treatments to patients and improve the prognosis of cancers.

PMID- 28451551
TI  - An Ethical Review of Euthanasia and Physician-assisted Suicide.
AB  - BACKGROUND: In the majority of countries, active direct euthanasia is a forbidden
      way of the deprivation of the patients' life, while its passive form is commonly
      accepted. This distinction between active and passive euthanasia has no
      justification, viewed through the prism of morality and ethics. Therefore, we
      focused on attention on the moral and ethical implications of the aforementioned
      medical procedures. METHODS: Data were obtained from the Clinical Hospital Center
      in Kragujevac, collected during the first half of the 2015. The research included
      88 physicians: 57 male physicians (representing 77% of the sample) and 31 female
      physicians (23% of the sample). Due to the nature, subject and hypothesis of the
      research, the authors used descriptive method and the method of the theoretical
      content analysis. RESULTS: A slight majority of the physicians (56, 8%) believe
      that active euthanasia is ethically unacceptable, while 43, 2% is for another
      solution (35, 2% took a viewpoint that it is completely ethically acceptable,
      while the remaining 8% considered it ethically acceptable in certain cases). From
      the other side, 56, 8% of respondents answered negatively on the ethical
      acceptability of the physician-assisted suicide, while 33% of them opted for a
      completely ethic viewpoint of this procedure. Out of the remaining 10, 2% opted
      for the ethical acceptability in certain cases. CONCLUSION: Physicians in Serbia
      are divided on this issue, but a group that considers active euthanasia and
      physician-assisted suicide as ethically unacceptable is a bit more numerous.

PMID- 28451552
TI  - Rehabilitation Nursing for Cerebral Stroke Patients within a Suitable Recovery
      Empty Period.
AB  - BACKGROUND: We aimed to research the value of extended nursing for cerebral
      stroke patients within a suitable recovery empty period. METHODS: Seventy-two
      cerebral stroke patients were randomized to a control group or treatment group at
      the recovery period at Xuzhou Recovery Hospital, China in 2016. A recovery
      guidance exercise was applied to the control group for a set time, while a
      recovery guidance exercise combined with functional training were applied to the
      treatment group within the recovery empty period (at 6:00-7:00 a.m. and 7:00-8:00
      p.m.). The recovery effect was compared after three months. RESULTS: Following
      the three-month intervention, both the control and treatment groups' scores for
      the Fugl-Meyer balance evaluation and the Barthel indicator were increased. There
      was a statistically significant increase in the treatment group (P<0.05). Scores
      for the Self-Rating Depression Scale in both groups declined and the decline in
      the treatment group was statistically significant greater when compared to the
      control group (P<0.05). The total depression rate for the treatment group was
      significantly lower than the control group and the severe extent of depression in
      the treatment group was significantly less than the control group (P<0.05). Both
      groups' scores for the PSQI also decreased with a significantly greater increase
      in the treatment group (P<0.05). CONCLUSION: Extended nursing within a suitable
      recovery empty period can improve the patient's prognosis concerning physical
      activity and mood.

PMID- 28451553
TI  - Feed-forward Control Nursing Model in Expectant Treatment of Placenta Previa.
AB  - BACKGROUND: We studied the possible advantages of feed-forward control nursing
      model in the treatment of placenta previa. METHODS: We enrolled 60 pregnant women
      who were receiving treatment for expectant placenta previa between January 2010
      and January 2016 and randomly divided them into the control group and the
      observation group with 30 cases in each group. In the control group, we offered
      specialist nursing which included examination, body positioning, vaginal bleeding
      record, psychological consultation and medication observation. Feed-forward
      control nursing was applied in the observation group which included establishing
      feed-forward control nursing improvement team, conducting quality control of
      nursing defects and putting forward ideas for improvements and verifying
      improvement outcomes. RESULTS: The observation group got significantly higher
      success rate and lower complication rate compared with control group. Gestational
      age and fetal weights improved apparently in the observation group. When we
      compared the amount of postpartum bleeding and pregnancy bleeding in two groups
      we did not find any statistically significant difference (P>0.05). Patients'
      satisfaction rate toward our nursing services was much higher in the observation
      group and the rate of nursing errors was significantly lower in this group. All
      differences were statistically significant (P<0.05). CONCLUSION: Application of
      feed-forward control nursing model in the expectant treatment of placenta previa
      can improve treatment success rate, decrease complications and upgrade nursing
      quality.

PMID- 28451554
TI  - Nursing Project Management to Reduce the Operating Room Infection.
AB  - BACKGROUND: Nursing project management is widely used in different aspects of the
      society. However, whether the nursing project management can control the
      infections in the operation room (OR) is rarely reported. We evaluated the
      outcomes of surgical patients after implementing a nursing project management
      program to provide new scientific ways to manage the OR infections. METHODS:
      Overall, 382 patients, who underwent surgical treatment in Qilu Hospital of
      Shandong University, Shandong, China from May 2015 to January 2016, were enrolled
      as observation group. Besides, 347 cases were selected as control group. Patients
      in the observation group were treated with the nursing project management plan,
      while patients in the control group were treated with the routine operation-room
      nursing measures. The infection control rates in the OR, and the patient
      satisfaction with the nursing team postoperatively were both compared between the
      two groups of patients. RESULTS: The OR air, the surgical and personnel's hands
      surfaces were sampled for colony forming units, and all were found to be
      significantly of better quality (indicated by less colony forming units) in the
      observation group (P<0.001). In addition, there were 3 cases (0.79%) of post
      operation infections in the observation group, while 12 cases (3.46%) occurred in
      the control group. The overall infection rate of the observation group was
      significantly lower than that of the control group (P = 0.011); and the
      satisfaction of patients with the nursing team in the observation group was
      significantly higher than that of the patients in the control group (P = 0.001).
      CONCLUSION: It is worth popularizing and applying a good nursing project
      management plan for surgical patients in hospitals.

PMID- 28451555
TI  - Unintended Pregnancies, Their Outcome and Prior Usage of Contraception in
      Georgia.
AB  - BACKGROUND: Unintended pregnancy (UPr) with high rates of subsequent abortions
      remains an important problem around the world. Our aim was to determine the
      prevalence of UPrs in Georgia, their outcomes, and use of modern and traditional
      methods of contraception in women who terminated their UPrs by induced abortion
      (IAb) and identify potentially associated factors. METHODS: A Cross-sectional
      study, using stratified multistage sampling design, was conducted from Oct 2010
      through Feb 2011. By secondary data analysis in selected group of women (n=2692)
      association of predictor variables: area of residence, age, level of education,
      economic status of woman, ethnicity, and religion with independent variables:
      UPr, termination of UPr by IAb and prior usage of modern and traditional methods
      of contraception were examined. Descriptive statistics methods and multivariable
      logistic regression analysis were used. RESULTS: In Georgia, from the 2692
      interviewed women who had a pregnancy, 1068(39.7%) had a UPr in 2005-2010; the
      majority (n=913; 85.5%) of these UPr ended in an IAb. 31.4% (n=287) of those
      women used any method of contraception, with the majority (n=213; 74.2%) using a
      traditional method. With UPr were associated area of residence, level of
      education and age (P>0.05); with termination of UPr by IAb-ethnic origin
      (P<0.05); with use of contraception -area of residence, age, level of education,
      ethnicity and religion and with use of modern methods of contraception - age
      (P<0.05). CONCLUSION: Low rates of modern contraception use prior UPrs,
      terminated by IAb demands attention by healthcare providers. Factors associated
      with these outcomes shall be used to identify target group of women.

PMID- 28451556
TI  - Sensitivity and Specificity of Preschool Vision Screening in Iran.
AB  - BACKGROUND: To determine the sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) of the National Vision Screening
      Program for 7 yr old children in Iran. METHODS: In this cross-sectional study,
      eight cities in Iran were selected through multistage cluster sampling. Selected
      cities were Sari, Birjand, Ardabil, Mashhad, Bandar Abbas, Dezful, Yazd, and
      Arak, in Iran in 2013. Totally, 4614 schoolchildren were selected, 4106 of which
      participated in the study. An optometrist at the school site conducted all vision
      tests. Results were compared against those recorded on each child's health card.
      Those with an uncorrected visual acuity worse than 20/25 in at least one eye
      screened positive for a vision problem. RESULTS: 8.49% [95% confidence interval,
      7.65 to 9.39] of the examinees had a vision problem. The sensitivity rate of the
      school entry screening was 38.15% (95% CI, 33.01 to 43.50) and the specificity
      rate was 93.11 (95%CI 92.25 to 93.90). The positive and negative predictive
      values were 33.93 (29.24 to 38.88) and 94.19 (93.39 to 94.93), respectively.
      Sensitivity and specificity rates did not significantly differ between boys and
      girls. For the uncorrected visual acuity tested by public health care workers
      compared to optometrists, the area under the ROC surface was 0.741 (P<0.001). The
      best-associated criterion was an uncorrected visual acuity more than 0.05 LogMAR
      with 67.3% sensitivity and 74.7% specificity. CONCLUSION: The validity of the
      school entry vision screening by health workers is low. To reduce false negative
      rates, some supplementary examinations such as refraction and near visual acuity
      measurements as well as further training of screeners should be considered.

PMID- 28451557
TI  - Efficacy and Safety of G2013 as a Novel Immunosuppressive Agent on
      Differentiation, Maturation and Function of Human Dendritic Cells.
AB  - BACKGROUND: The expanse of dendritic cells (DC) differentiation plays an
      important role in determining immune response. DC-based immunosuppressive drugs
      have notable side effects in increasing the risk of infectious diseases and
      cancers. G2013, as a novel anti-inflammatory and immunosuppressive agent, has
      been tested in experimental model of multiple sclerosis. The aim of this study
      was to conduct the safety property of G2013 on dendritic cells biology. METHODS:
      The effect of G2013 on differentiation, maturation, and function of dendritic
      cells was examined at Tehran University in 2014. To investigate how G2013 affects
      human dendritic cells (DC) in a defined inflammatory environment, human
      peripheral blood mononuclear cells (PBMC) were isolated from healthy blood.
      Monocytes were then purified using anti-CD14 microbeads. Monocytes were treated
      with G2013 in two different doses (6 and 12 MUg/well) along with adding
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 for
      inducing monocytes to immature DC and adding lipopolysaccharide for running DC
      maturation. Differentiation, maturation, and function of dendritic cells were
      examined with flow cytometry and ELISA. RESULTS: G2013 therapy had no significant
      effect on CD83, CD86 and DR expression, as well as IL-10 and IL-12 cytokine
      levels and it, has no remarkable side on differentiation, maturation and function
      of dendritic cells in immature DC and mature DC process in vitro. CONCLUSION:
      G2013 is a safe agent with no adverse effect on differentiation, maturation, and
      function of dendritic cells. It may be recommended as a novel immunosuppressive
      agent with no or little side effect in increasing the risk of infectious diseases
      and cancers.

PMID- 28451558
TI  - Comparison of Two Different PCR-based Methods for Detection of GAA Expansions in
      Frataxin Gene.
AB  - BACKGROUND: Expansion of GAA trinucleotide repeats is the molecular basis of
      Friedreich's ataxia (FRDA). Precise detection of the GAA expansion repeat in
      frataxin gene has always been a challenge. Different molecular methods have been
      suggested for detection of GAA expansion, including; short-PCR, long-PCR, Triplet
      repeat primed-PCR (TP-PCR) and southern blotting. The aim of study was to
      evaluate two PCR-based methods, TP-PCR and long-PCR, and to explore the use of TP
      PCR accompanying with long-PCR for accurate genotyping of FRDA patients. METHODS:
      Blood samples were collected from six Iranian patients suspected to FRDA, who
      referred to the Department of Medical Genetics at Tehran University of Medical
      Sciences during the year 2014. For one of these patients' four asymptomatic
      members of the family were also recruited for the analysis. DNA extraction was
      performed by two different methods. TP-PCR and long-PCR were carried out in all
      samples. The type of this study is assessment / investigation of methods.
      RESULTS: Using a combination of the above methods, the genotypes of all samples
      were confirmed as five homozygous mutants (expanded GAA repeats), two
      heterozygous and three homozygous normal (normal repeat size). The results
      obtained by TP-PCR are consistent with long-PCR results. CONCLUSION: The presence
      or absence of expanded alleles can be identified correctly by TP-PCR. Performing
      long-PCR and Fluorescent-long-PCR enables accurate genotyping in all samples.
      This approach is highly reliable. It could be successfully used for detection of
      GAA expansion repeats.

PMID- 28451559
TI  - Effect of Sodium Arsenite on the Expression of Antioxidant Genes (SOD2 and CAT)
      in MCF-7 and Jurkat Cell Lines.
AB  - BACKGROUND: Sodium arsenite (NaAsO2) has potent cytotoxic activity in human
      cancer cells. Oxidative stress has been suggested as a mechanism for arsenic
      induced carcinogenesis. The purpose of the present study was to evaluate the
      alteration of mRNA levels of catalase (CAT) and superoxide dismutase 2 (SOD2) in
      MCF-7 and Jurkat cells after exposure to NaAsO2. METHODS: Methylthiazol
      tetrazolium (MTT) viability assay was performed to evaluate cytotoxicity of
      NaAsO2 in MCF-7 and Jurkat cells. For evaluating the expression levels of the CAT
      and SOD2, we used two concentrations of NaAsO2 (5 and 15 MUM), lower than the
      concentrations at which 50% of cell viability were lost. The cells were treated
      with co-treatment of NaAsO2 (15 MUM) and N-acetyl-cysteine (NAC; 5 MUM) in the
      media for 24 h. The control cells were maintained in sodium arsenite free growth
      medium. The experiments were done triplicate. Using quantitative real-time PCR,
      the expression levels of CAT and SOD2 were quantified. One sample student's t
      test was performed for comparisons of mRNA levels between treatment groups and
      their corresponding untreated control cells. RESULTS: CAT mRNA level decreased
      significantly in both cell lines following exposure to NaAsO2 (P<0.05).
      Expression levels of SOD2 decreased in Jurkat cells and increased in MCF-7 cells
      after treatment with NaAsO2 (P<0.05). CONCLUSION: After cells exposure to NaAsO2,
      CAT mRNA level decreased in both examined cell lines but the alterations of SOD2
      mRNA level is cell specific. The NAC modulated the NaAsO2 associated alterations
      of CAT and SOD2 mRNA levels, therefore, the NaAsO2 might act through inducing
      reactive oxygen species.

PMID- 28451560
TI  - Caspofungin-Non-Susceptible Candida orthopsilosis Isolated from Onychomycosis in
      Iran.
AB  - BACKGROUND: Although Candida albicans remains the most common fungal isolate from
      clinical specimens, many studies have detected a shift towards non-albicans
      Candida species. Despite worrying clinical pictures associated with latter
      species, there is little information regarding its susceptibility patterns
      against currently available antifungal agents, with only a small number of
      strains having been studied. METHODS: We evaluated the in vitro antifungal
      susceptibilities of clinical isolates of C. orthopsilosis already identified by
      two-steps PCR-RFLP and reconfirmed by sequence analysis of entire ITS rDNA
      region, to six antifungal drugs. RESULTS: The resulting MIC50 and MIC90 for all
      strains (n=18) were in increasing order, as follows: posaconazole (0.016 & 0.063
      MUg/ml); itraconazole (0.031 & 0.125 MUg/ml); amphotericin B (0.5 & 1 MUg/ml);
      fluconazole (0.25 & 0.5 MUg/ml) and caspofungin (4 & 8 MUg/ml). A uniform pattern
      of the MIC ranges was seen for amphotericin B, fluconazole, itraconazole, and
      posaconazole, while a widest range and the highest MICs were observed for
      caspofungin. CONCLUSION: Although we emphasis on the careful species designation
      of the clinical isolates of Candida, the antifungal susceptibility patterns of
      these clinically important organisms may have an application in clinical and
      epidemiological setting and deserve the implementation of local surveillance
      programs to monitor.

PMID- 28451561
TI  - Postnatal Care: Levels and Determinants in Morocco.
AB  - BACKGROUND: Despite the importance of the postnatal consultation, in Morocco,
      only 22% of women attended these consultations. The aim of this study was to
      identify associated factors with these consultations and offer suggestions to
      improve their use. METHODS: This study was conducted in 2014 in Marrakech. A
      sample of women in reproductive age (15-49 yr) giving birth during 2013 year was
      enrolled. They were examined in the public health centers for postnatal
      consultation or for the BCG. A descriptive and analytic cross-sectional survey
      was conducted. All participants (n=1029) provided consent before participating in
      the survey. A questionnaire makes it possible to collect information about socio
      demographic, knowledge and perception of women regarding these consultations.
      RESULTS: The proportion of women who attended a postnatal consultation was 30.1%.
      Lack of information (87%), lack of complications (68.6%); health professional
      poor reception (42%) and financial difficulties (3.3%) were the main reasons that
      hinder these consultations. In addition, women of rural origin, low education
      level, and low socioeconomic status are important determinants associated with
      non-use of postnatal consultation. CONCLUSION: This study confirmed the low rate
      of these consultations. Various determinants explain this fact. The fight against
      illiteracy, improving household living standards, sensitization of women on the
      importance of postpartum care, awareness and capacity building of health
      professionals in the postnatal consultation and communication, and the
      development of a system of home visits for non-users of postnatal care allow
      improving the postnatal consultation rate.

PMID- 28451562
TI  - Designing a Medical Tourism Website: A Qualitative Study.
AB  - BACKGROUND: Informing plays a prominent role in attracting medical tourists. The
      enjoyment of proper medical information systems is one of the most important
      tools for the attraction of medical tourists. Iran's ability in designing and
      implementing information networks has remained largely unknown. The current study
      aimed to explore information needs for designing a medical tourism website.
      METHODS: This qualitative study was conducted in 2015 for designing Hospital
      Medical-Tourism Website (HMTW). A purposive sampling method was used and data
      were gathered using a semi-structured questionnaire. Totally, 12 faculty members
      and experts in the field of medical tourism were interviewed. Data were analyzed
      using the MAXQDA10 software. RESULTS: Totally 41 sub-themes and 10 themes were
      identified. The themes included the introduction of hospital, general guide for
      patients, tourism information, information related to physicians in hospital,
      costs, treatment follow-up, online hospital appointment scheduling in website,
      statistics and news of hospital medical tourism, photo gallery and contacts.
      Among the themes, the participants highly emphasized four themes including costs
      (100%), tourism information (91.6%), information related to physicians in
      hospital, (83.3%) and treatment follow-up (83.3%). CONCLUSION: This profitable
      industry can be developed through considering information requirements for
      hospital medical tourism website.

PMID- 28451563
TI  - Pachydermodactyly with Broder Hand Span and Long Fingers: A Case Report.
AB  - Pachydermodactyly is a rare and benign disease that may be idiopathic, genetic,
      acquired as a response to repetitive trauma, or associated with several other
      acquired conditions often pushing the health caregiver to do a bunch of costly
      lab tests and diagnostic workups to rule out other entities. All health care
      givers must be aware about this disease for reassure the patients and cut
      unnecessary costs. Moreover, there seems to be an issue of association with
      certain occupations. A good example might be computer keyboards causing special
      damages to certain organs like eyes and musculoskeletal system. We have observed
      deleterious effects of excess work with computer keyboards on fingers in the form
      of Pachydermodactyly in our case. A 27-yr-old man presented with wider hand span
      and longer fingers to Dermatology Clinic of Rasoul-E-Akram Hospital in June 2015,
      especially the ring finger in our case, considered a big symptom who depressed
      due to their fingers appearance as a rare disease. We gave him an emollient to
      make his hand smoother. The patient improved both clinically and psychologically
      on a simple emollient. This disease with its deleterious psychological effects
      and a simple way of management should be appreciated more by the health care
      system.

PMID- 28451564
TI  - Eyelid Cutaneous Leishmaniasis: A Case Report.
AB  - Cutaneous leishmaniasis (CL) is the most common parasitic disease transmitted by
      vectors in Iran. CL is endemic in many urban and rural parts of Iran and usually
      caused by two species of Leishmania as L. major and L. tropica transmitted to
      humans from parasite reservoirs by the bite of female sandflies. We report a case
      of ocular leishmaniasis with eyelid involvement presentation. The patient was a
      70-yr-old housewife woman referred to Health Care Center in city of Kashan,
      central Iran in 2012. The disease was diagnosed by direct smear, culture, and PCR
      from the lesion. PCR was positive for L. major. Her lesion was treated with
      systemic meglumine antimonate (Glucantime) (20 mg/kg/day) for 20 days.

PMID- 28451566
TI  - An Insight to How Estate Women in Sri Lanka Manage Abnormal Vaginal Discharge.

PMID- 28451565
TI  - Oropharyngeal Airway Three-dimensional Changes after Treatment with Myobrace in
      Class II Retrognathic Children.

PMID- 28451567
TI  - Changes in Blood Lactate Levels after a 40-km Endurance March Depend on Fluid
      Replacements: A Case Study on Korean Military Academy Cadets.

PMID- 28451568
TI  - Choosing from Whole Cell and Acellular Pertussis Vaccines-Dilemma for the
      Developing Countries.

PMID- 28451569
TI  - Today's Public Health Issue: Workaholism.

PMID- 28451570
TI  - A Study on Hospitalized Patients' Payment in South of Iran after the First Round
      of Health Sector Reform.

PMID- 28451571
TI  - The Reality behind Informal Health Payments in Iran: "Under the Table Payments"
      or "On the Table Payments"?

PMID- 28451573
TI  - Reply to Comments on Paper Published in IJPH as "Factors Associated with Physical
      Activity among Macedonian Adolescents ..."

PMID- 28451572
TI  - Comments on Paper Published in IJPH as "Factors Associated with Physical Activity
      among Macedonian Adolescents ..."

PMID- 28451574
TI  - Evaluation of Radiation Exposure to Staff and Environment Dose from [18F]-FDG in
      PET/CT and Cyclotron Center using Thermoluminescent Dosimetry.
AB  - BACKGROUND: PET/CT imaging using [18F]-FDG is utilized in clinical oncology for
      tumor detecting, staging and responding to therapy procedures. Essential
      consideration must be taken for radiation staff due to high gamma radiation in
      PET/CT and cyclotron center. The aim of this study was to assess the staff
      exposure regarding whole body and organ dose and to evaluate environment dose in
      PET/CT and cyclotron center. MATERIALS AND METHODS: 80 patients participated in
      this study. Thermoluminescence, electronic personal dosimeter and Geiger-Muller
      dosimeter were also utilized for measurement purpose. RESULTS: The mean annual
      equivalent organ dose for scanning operator with regard to lens of eyes, thyroid,
      breast and finger according to mean+/-SD value, were 0.262+/-0.044, 0.256+/
      0.046, 0.257+/-0.040 and 0.316+/-0.118, respectively. The maximum and minimum
      estimated annual whole body doses were observed for injector and the chemist
      group with values of (3.98+/-0.021) mSv/yr and (1.64+/-0.014) mSv/yr,
      respectively. The observed dose rates were 5.67 uSv/h in uptake room at the
      distance of 0.5 meter from the patient whereas the value 4.94 and 3.08 uSv/h were
      recorded close to patient's head in PET/CT room and 3.5 meter from the reception
      desk. CONCLUSION: In this study, the injector staff and scanning operator
      received the first high level and second high level of radiation. This study
      confirmed that low levels of radiation dose were received by all radiation staff
      during PET/CT procedure using 18F-FDG due to efficient shielding and using
      trained radiation staff in PET/CT and cyclotron center of Masih Daneshvari
      hospital.

PMID- 28451575
TI  - A Monte Carlo Study on the Effect of Various Neutron Capturers on Dose
      Distribution in Brachytherapy with 252Cf Source.
AB  - BACKGROUND: In neutron interaction with matter and reduction of neutron energy
      due to multiple scatterings to the thermal energy range, increasing the
      probability of thermal neutron capture by neutron captures makes dose enhancement
      in the tumors loaded with these materials. OBJECTIVE: The purpose of this study
      is to evaluate dose distribution in the presence of 10B, 157Gd and 33S neutron
      capturers and to determine the effect of these materials on dose enhancement rate
      for 252Cf brachytherapy source. METHODS: Neutron-ray flux and energy spectra,
      neutron and gamma dose rates and dose enhancement factor (DEF) are determined in
      the absence and presence of 10B, 157Gd and 33S using Monte Carlo simulation.
      RESULTS: The difference in the thermal neutron flux rate in the presence of 10B
      and 157Gd is significant, while the flux changes in the fast and epithermal
      energy ranges are insensible. The dose enhancement factor has increased with
      increasing distance from the source and reached its maximum amount equal to 258.3
      and 476.1 cGy/h/ug for 157Gd and 10B, respectively at about 8 cm distance from
      the source center. DEF for 33S is equal to one. CONCLUSION: Results show that the
      magnitude of dose augmentation in tumors containing 10B and 157Gd in
      brachytherapy with 252Cf source will depend not only on the capture product dose
      level, but also on the tumor distance from the source. 33S makes dose enhancement
      under specific conditions that these conditions depend on the neutron energy
      spectra of source, the 33S concentration in tumor and tumor distance from the
      source.

PMID- 28451576
TI  - Thyroid Ultrasonography in Differentiation between Graves' Disease and
      Hashimoto's Thyroiditis.
AB  - OBJECTIVE: Graves' disease and Hashimoto's thyroiditis are the most common causes
      of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases,
      if the patient is euthyroid, may sometimes be extremely difficult on the basis of
      clinical and laboratory findings. The purpose of this study was to determine the
      sensitivity and specificity of gray scale sonography in differentiation of
      Graves' disease from Hashimoto's thyroiditis. METHODS: This study included 149
      patients divided into three groups, patients with Graves' disease (34 patients,
      mean age = 36.8 +/- 10.17 years), Patients with Hashimoto's thyroiditis (62
      patients, mean age = 33.4 +/- 12.16 years) and control group (53 healthy people,
      mean age = 34.74 +/- 16.87 years). Members of all groups were referred to a
      single radiologist for thyroid sonography for evaluation of thyroid echogenicity
      pattern. RESULTS: A total of 117 women and 32 men were examined by sonography.
      The most common sonographic pattern in Hashimoto and Graves' was homogenous hypo
      echogenicity which was observed in 45.2% and 47.1% of cases, respectively.
      Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto's group with
      100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was
      observed in 17.6% of Graves' group with 100% and 17.6% specificity and
      sensitivity, respectively. CONCLUSION: Our findings indicate that sonography has
      high specificity but low sensitivity in the diagnosis of either Graves' disease
      or Hashimoto's thyroiditis. It is therefore not possible to differentiate between
      these two diseases using sonography alone. Confirmation by laboratory data is
      also needed.

PMID- 28451577
TI  - Expression Levels of Two DNA Repair-related Genes under 8 Gy Ionizing Radiation
      and 100 Mg/Kg Melatonin Delivery In Rat Peripheral Blood.
AB  - BACKGROUND: After radiation therapy (RT), some health hazards including DNA
      damages may occur where melatonin can play a protective role due to free radical
      generation. On the other hand, serious accidental overexposures may occur during
      RT due to nuclear accidents which necessitate the need for study on exposure to
      high-dose radiations during treatments. OBJECTIVE: The aim of this study was to
      study the expression level of two genes in non-homologous end joining (NHEJ)
      pathways named Xrcc4 and Xrcc6 (Ku70) in order to examine the effect of melatonin
      on repair of DNA double-strand breaks (BSBs) caused by 8Gy ionizing radiation.
      METHODS: One hundred eight male Wistar rats were irradiated with a whole body
      gamma radiation dose of 8Gy with or without melatonin pretreatments. They were
      divided into six different groups of control, 100 mg/kg melatonin alone, 8Gy
      irradiation alone, vehicle alone, vehicle plus 8Gy irradiation and 100 mg/kg
      melatonin plus 8Gy irradiation. Peripheral blood samples were collected at 8, 24
      and 48 h after irradiation. Ku70 and Xrcc4 gene expression were evaluated by real
      time quantitative polymerase chain reaction (qPCR) technique and analyzed by one
      way ANOVA test. RESULTS: Expression of Ku70 and Xrcc4 genes normalized against
      Hprt gene showed significant difference in melatonin plus irradiation group at 8h
      compared to the control group (p<0.05). At 24h post irradiation, gene expression
      changes were significantly upregulated in irradiation-alone group as well as
      melatonin plus irradiation group (p<0.05). No significant change was found in any
      groups compared to control group at 48 h time point. CONCLUSION: We concluded
      that, by increasing expression level of Ku70 and Xrcc4 genes, 100 mg/kg melatonin
      administration 8 and 24 h before 8 Gyionizing radiation can significantly affect
      the repair of DNA DSBs in NHEJ pathway.

PMID- 28451578
TI  - A PCA/ICA based Fetal ECG Extraction from Mother Abdominal Recordings by Means of
      a Novel Data-driven Approach to Fetal ECG Quality Assessment.
AB  - BACKGROUND: Fetal electrocardiography is a developing field that provides
      valuable information on the fetal health during pregnancy. By early diagnosis and
      treatment of fetal heart problems, more survival chance is given to the infant.
      OBJECTIVE:  MATERIALS AND METHODS: Here, we extract fetal ECG from maternal
      abdominal recordings and detect R-peaks in order to recognize fetal heart rate.
      On the next step, we find a better and more qualified extracted fetal ECG by
      using a novel approach. RESULTS: In this paper, a PCA/ICA-based algorithm is
      proposed for extracting fetal ECG, and fetal R-peaks are detected as well. The
      method validates the quality of extracted ECGs and selects the best candidate
      fetal ECG to provide the required morphological ECG features such as fetal heart
      rate and RR interval for more clinical examinations. The method was evaluated
      using the dataset which was provided by PhysioNet/Computing in Cardiology
      Challenge 2013. The dataset consists of 75 recordings of 4-channel ECGs each
      containing 1-minute length for training and 100 similar recordings for testing.
      CONCLUSION: When the proposed algorithm was applied to the test set, the scores
      of 85.853 bpm2 for fetal heart rate and an error of 9.725 ms RMS for fetal RR
      interval estimation were obtained.

PMID- 28451579
TI  - Comparative Analysis of Neural Network Training Methods in Real-time
      Radiotherapy.
AB  - BACKGROUND: The motions of body and tumor in some regions such as chest during
      radiotherapy treatments are one of the major concerns protecting normal tissues
      against high doses. By using real-time radiotherapy technique, it is possible to
      increase the accuracy of delivered dose to the tumor region by means of tracing
      markers on the body of patients. OBJECTIVE: This study evaluates the accuracy of
      some artificial intelligence methods including neural network and those of
      combination with genetic algorithm as well as particle swarm optimization (PSO)
      estimating tumor positions in real-time radiotherapy. METHOD: One hundred
      recorded signals of three external markers were used as input data. The signals
      from 3 markers thorough 10 breathing cycles of a patient treated via a cyber
      knife for a lung tumor were used as data input. Then, neural network method and
      its combination with genetic or PSO algorithms were applied determining the tumor
      locations using MATLAB(c) software program. RESULTS: The accuracies were obtained
      0.8%, 12% and 14% in neural network, genetic and particle swarm optimization
      algorithms, respectively. CONCLUSION: The internal target volume (ITV) should be
      determined based on the applied neural network algorithm on training steps.

PMID- 28451580
TI  - A Wireless Electronic Esophageal Stethoscope for Continuous Monitoring of
      Cardiovascular and Respiratory Systems during Anaesthesia.
AB  - BACKGROUND: The basic requirements for monitoring anesthetized patients during
      surgery are assessing cardiac and respiratory function. Esophageal stethoscopes
      have been developed for this purpose, but these devices may not provide clear
      heart and lung sound due to existence of various noises in operating rooms. In
      addition, the stethoscope is not applicable for continues monitoring, and it is
      unsuitable for observing inaccessible patients in some conditions such as during
      CT scan. OBJECTIVE: A wireless electronic esophageal stethoscope is designed for
      continues auscultation of heart and lung sounds in anesthetized patients. The
      system consists of a transmitter and a receiver. The former acquires, amplifies
      and transmits the acquired sound signals to the latter via a frequency modulation
      transmitter. The receiver demodulates, amplifies, and delivers the received
      signal to a headphone to be heard by anesthesiologist. RESULTS: The usability and
      effectiveness of the designed system was qualitatively evaluated by 5
      anesthesiologists in Namazi Hospital and Shahid Chamran Hospital, Shiraz, Iran on
      30 patients in several operating rooms in different conditions; e.g., when
      electro surgery instruments are working. Fortunately, the experts on average
      ranked good quality for the heard heart and lung sounds and very good on the user
      friendly being of the instrument. CONCLUSION: Evaluation results demonstrate that
      the developed system is capable of capturing and transmitting heart and lung
      sounds successfully. Therefore, it can be used to continuously monitor
      anesthetized patients' cardiac and respiratory function. Since via the instrument
      wireless auscultation is possible, it could be suitable for observing
      inaccessible patients in several conditions such as during CT scan.

PMID- 28451581
TI  - Effect of Exposure to 900 MHz GSM Mobile Phone Radiofrequency Radiation on
      Estrogen Receptor Methylation Status in Colon Cells of Male Sprague Dawley Rats.
AB  - BACKGROUND: Over the past several years, the rapidly increasing use of mobile
      phones has raised global concerns about the biological effects of exposure to
      radiofrequency (RF) radiation. Numerous studies have shown that exposure to
      electromagnetic fields (EMFs) can be associated with effects on the nervous,
      endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of
      genetic diversity, the onset and progression of cancer can be controlled by
      epigenetic mechanisms such as gene promoter methylation. There are extensive
      studies on the epigenetic changes of the tumor suppressor genes as well as the
      identification of methylation biomarkers in colorectal cancer. Some studies have
      revealed that genetic changes can be induced by exposure to RF radiation.
      However, whether or not RF radiation is capable of inducing epigenetic alteration
      has not been clarified yet. To date, no study has been conducted on the effect of
      radiation on epigenetic alterations in colorectal cancer (CRC). Several studies
      have also shown that methylation of estrogen receptor alpha (ERalpha), MYOD,
      MGMT, SFRP2 and P16 play an important role in CRC. It can be hypothesized that RF
      exposure can be a reason for the high incidence of CRC in Iran. This study aimed
      to investigate whether epigenetic pattern of ERalpha is susceptible to RF
      radiation and if RF radiation can induce radioadaptive response as epigenetic
      changes after receiving the challenge dose (gamma-ray). MATERIAL AND METHOD: 40
      male Sprague-Dawley rats were divided into 4 equal groups (Group I: exposure to
      RF radiation of a GSM cell phone for 4 hours and sacrificed after 24 hours; Group
      II: RF exposure for 4 hours, exposure to Co-60 gamma radiation (3 Gy) after 24
      hours and sacrificed after 72 hrs; Group III: only 3Gy gamma radiation; Group 4:
      control group). DNA from colon tissues was extracted to evaluate the methylation
      status by methylation specific PCR. RESULTS: Our finding showed that exposure to
      GSM cell phone RF radiation was capable of altering the pattern of ERalpha gene
      methylation compared to that of non-exposed controls. Furthermore, no adaptive
      response phenomenon was induced in the pattern of ERalpha gene methylation after
      exposure to the challenging dose of Co-60 gamma-rays. CONCLUSION: It can be
      concluded that exposure to RF radiation emitted by GSM mobile phones can lead to
      epigenetic detrimental changes in ERalpha promoter methylation pattern.

PMID- 28451582
TI  - Smart Phone Acceptance among Physicians: Application of Structural Equation
      Modelling in the Largest Iranian University.
AB  - BACKGROUND: The present study aimed to determine attitudes and effective factors
      in the acceptance of smart phones by physicians of the largest University of
      Medical Sciences in the south of Iran. METHODS: This cross-sectional study was
      performed using Structural Equation Modelling (SEM) in 2014. Study participants
      included 200 physicians working in the hospitals of Shiraz University of Medical
      Sciences selected through two-stage stratified sampling, but 185 participants
      completed the study. The study data were collected using a researcher-made
      questionnaire completed through a 5-point Likert scale. The content validity of
      the questionnaire was confirmed by a panel of experts, its construct validity by
      confirmatory factor analysis, and its reliability by Cronbach's alpha of 0.802.
      All data analyses were performed using SPSS (version 22) and LISREL (version
      8.8). RESULTS: Results showed that most physicians had a desirable attitude
      towards using smart phones. Besides, the results of SEM indicated a significant
      relationship between attitude and compatibility, observability, personal
      experience, voluntariness of use and perceived usefulness. Moreover, some
      important fitness indices revealed appropriate fitness of the study model
      (p=0.26, X2/df=1.35, RMR=0.070, GFI=0.77, AGFI=0.71, NNFI=0.93, CFI=0.94).
      CONCLUSION: The results revealed that compatibility, observability, personal
      experience, voluntariness of use and perceived usefulness were effective in the
      physicians' attitude towards using smart phones. Thus, by preparation of the
      required infrastructures, policymakers in the field of health technology can
      enhance the utilization of smart phones in hospitals.

PMID- 28451584
TI  - Overweight and Obesity in Children under 5 Years: Surveillance Opportunities and
      Challenges for the WHO European Region.
AB  - BACKGROUND: Many children who have overweight or obesity before puberty can
      develop obesity in early adulthood, which is associated with increased morbidity
      and mortality. The preschool years (ages 0-5) represents a point of opportunity
      for children to be active, develop healthy eating habits, and maintain healthy
      growth. Surveillance of childhood overweight and obesity in this age group can
      help inform future policies and interventions. OBJECTIVE: To review and report
      available prevalence data in WHO European Region Member States and determine how
      many countries can accurately report on rates of overweight and obesity in
      children under 5 years. METHODS: We conducted a rapid review of studies reporting
      on overweight and obesity prevalence in children ages 0-5 in the WHO European
      region member states from 1998 to 2015. RESULTS: Currently, 35 of the 53 member
      states have data providing prevalence rates for overweight and obesity for
      children under 5 years. There was little consistency in study methods, impacting
      comparability across countries. The prevalence of overweight and obesity in
      children under 5 years ranges from 1 to 28.6% across member states. CONCLUSION:
      Although measuring overweight and obesity in this age group may be challenging,
      there is an opportunity to leverage existing surveillance resources in the WHO
      European Region.

PMID- 28451585
TI  - Where Are They Now? Evolution of a Nurse Anesthesia Training School in Ghana and
      a Survey of Graduates.
AB  - Ghana, like other countries in sub-Saharan African, has limited access to
      surgery. One contributing factor is the inadequate number of anesthesia
      providers. To address this need, Kybele, Inc., a US-based non-governmental
      organization, partnered with the Ghana Health Service to establish the third
      nurse anesthesia training school (NATS) in Ghana. The school, based at Ridge
      Regional Hospital (RRH) in Accra, opened in October 2009. This paper describes
      the evolution of the training program and presents the curriculum. Second, the
      results of a voluntary survey conducted among the first four classes of graduates
      (2011-2014) are presented to determine their perceived strengths and gaps in
      training and to identify employment locations and equipment availability. Seventy
      five of 93 graduates (81%) responded to the survey. The graduates reported
      working in 39 hospitals across 7 of the 10 regions in Ghana. Six providers (8%)
      worked alone and 16 (21%) were one of only two providers. Fifty-three providers
      (71%) had no physician anesthesiologist at their facility. Most providers had
      access to basic anesthesia equipment; however, there was limited access to
      emergency airway equipment. While most graduates felt that their training had
      prepared them for their current positions, 21% reported experiencing a patient
      death during anesthesia. The NATS at RRH has been sustained and most of the
      graduates are working in Ghana, filling an important void. Quality improvement
      and continuing education must be emphasized in an effort to reduce surgical
      morbidity and mortality in Ghana.

PMID- 28451583
TI  - Pregnancy: An Underutilized Window of Opportunity to Improve Long-term Maternal
      and Infant Health-An Appeal for Continuous Family Care and Interdisciplinary
      Communication.
AB  - Physiologic adaptations during pregnancy unmask a woman's predisposition to
      diseases. Complications are increasingly predicted by first-trimester algorithms,
      amplify a pre-existing maternal phenotype and accelerate risks for chronic
      diseases in the offspring up to adulthood (Barker hypothesis). Recent evidence
      suggests that vice versa, pregnancy diseases also indicate maternal and even
      grandparent's risks for chronic diseases (reverse Barker hypothesis). Pub-Med and
      Embase were reviewed for Mesh terms "fetal programming" and "pregnancy
      complications combined with maternal disease" until January 2017. Studies linking
      pregnancy complications to future cardiovascular, metabolic, and thrombotic risks
      for mother and offspring were reviewed. Women with a history of miscarriage,
      fetal growth restriction, preeclampsia, preterm delivery, obesity, excessive
      gestational weight gain, gestational diabetes, subfertility, and thrombophilia
      more frequently demonstrate with echocardiographic abnormalities, higher fasting
      insulin, deviating lipids or clotting factors and show defective endothelial
      function. Thrombophilia hints to thrombotic risks in later life. Pregnancy
      abnormalities correlate with future cardiovascular and metabolic complications
      and earlier mortality. Conversely, women with a normal pregnancy have lower rates
      of subsequent diseases than the general female population creating the term:
      "Pregnancy as a window for future health." Although the placenta works as a
      gatekeeper, many pregnancy complications may lead to sickness and earlier death
      in later life when the child becomes an adult. The epigenetic mechanisms and the
      mismatch between pre- and postnatal life have created the term "fetal origin of
      adult disease." Up to now, the impact of cardiovascular, metabolic, or thrombotic
      risk profiles has been investigated separately for mother and child. In this
      manuscript, we strive to illustrate the consequences for both, fetus and mother
      within a cohesive perspective and thus try to demonstrate the complex
      interrelationship of genetics and epigenetics for long-term health of societies
      and future generations. Maternal-fetal medicine specialists should have a key
      role in the prevention of non-communicable diseases by implementing a framework
      for patient consultation and interdisciplinary networks. Health-care providers
      and policy makers should increasingly invest in a stratified primary prevention
      and follow-up to reduce the increasing number of manifest cardiovascular and
      metabolic diseases and to prevent waste of health-care resources.

PMID- 28451586
TI  - Temporal Information Entropy of the Blood-Oxygenation Level-Dependent Signals
      Increases in the Activated Human Primary Visual Cortex.
AB  - Time-domain analysis of blood-oxygenation level-dependent (BOLD) signals allows
      the identification of clusters of voxels responding to photic stimulation in
      primary visual cortex (V1). However, the characterization of information encoding
      into temporal properties of the BOLD signals of an activated cluster is poorly
      investigated. Here, we used Shannon entropy to determine spatial and temporal
      information encoding in the BOLD signal within the most strongly activated area
      of the human visual cortex during a hemifield photic stimulation. We determined
      the distribution profile of BOLD signals during epochs at rest and under
      stimulation within small (19-121 voxels) clusters designed to include only voxels
      driven by the stimulus as highly and uniformly as possible. We found consistent
      and significant increases (2-4% on average) in temporal information entropy
      during activation in contralateral but not ipsilateral V1, which was mirrored by
      an expected loss of spatial information entropy. These opposite changes coexisted
      with increases in both spatial and temporal mutual information (i.e., dependence)
      in contralateral V1. Thus, we showed that the first cortical stage of visual
      processing is characterized by a specific spatiotemporal rearrangement of
      intracluster BOLD responses. Our results indicate that while in the space domain
      BOLD maps may be incapable of capturing the functional specialization of small
      neuronal populations due to relatively low spatial resolution, some information
      encoding may still be revealed in the temporal domain by an increase of temporal
      information entropy.

PMID- 28451588
TI  - Lead Extraction of Cardiac Rhythm Devices: A Report of a Single-Center
      Experience.
AB  - INTRODUCTION AND OBJECTIVES: The rate of implanted cardiac electronic devices is
      increasing as is the need to manage long-term complications. Lead removal is
      becoming an effective approach to treat such complications. We present our
      experience in lead removal using different approaches, analyzing the predictors
      of the use of mechanical extractors/surgical removal. METHODS: Retrospective
      analysis of lead extractions in a series of 76 consecutive patients (mean age
      70.4 +/- 13.8 years, 73.7% men) between January 2009 and November 2015. RESULTS:
      One hundred thirty-five leads from permanent pacemakers (single chamber 19.7%;
      dual-chamber 61.8%), implantable cardioverter defibrillators (5.3%), and cardiac
      resynchronization devices (CRT-P 2.6%; CRT-D 7.9%) were removed, 72.5 +/- 73.2
      months after implantation. A total of 45.9% were ventricular leads, 40.0% atrial
      leads, 8.9% defibrillator leads, and 5.2% leads in the coronary sinus; 64.4% had
      passive fixation. The most common indications for removal were pocket infection
      (77.8%), infective endocarditis (9.6%), and lead dislodgement (3.7%). A total of
      76.3% of the leads were explanted, 20.0% were extracted, and 3.7% were surgically
      removed. Extraction of the entire lead was achieved in 96.3% of the procedures.
      After logistic regression (age adjusted), time since implantation was the sole
      predictor of the need of mechanical extractors/surgical removal. All patients
      were discharged without major complications. There were no deaths at 30 days.
      CONCLUSION: Our experience in lead removal was effective and safe. Performing
      these procedures by experienced electrophysiologists with an adequate
      cardiothoracic surgery team on standby to cope with any complications is
      required. Referral of high-risk patients to a high-volume center is recommended
      to optimize clinical success and minimize procedural complications.

PMID- 28451589
TI  - Rabies Vaccination Targets for Stray Dog Populations.
AB  - The role of stray dogs in the persistence of domestic dog rabies, and whether
      removal of such dogs is beneficial, remains contentious issues for control
      programs seeking to eliminate rabies. While a community might reach the WHO
      vaccination target of 70% for dogs that can be handled, the stray or neighborhood
      dogs that are too wary of humans to be held are a more problematic population to
      vaccinate. Here, we present a method to estimate vaccination targets for stray
      dogs when the dog population is made up of stray, free-roaming, and confined
      dogs, where the latter two types are considered to have an identifiable owner.
      The control effort required for stray dogs is determined by the type-reproduction
      number, T1, the number of stray dogs infected by one rabid stray dog either
      directly or via any chain of infection involving owned dogs. Like the basic
      reproduction number R0 for single host populations, T1 determines the vaccination
      effort required to control the spread of disease when control is targeted at one
      host type, and there is a mix of host types. The application of T1 to rabies in
      mixed populations of stray and owned dogs is novel. We show that the outcome is
      sensitive to the vaccination coverage in the owned dog population, such that if
      vaccination rates of owned dogs were too low then no control effort targeting
      stray dogs is able to control or eliminate rabies. The required vaccination level
      also depends on the composition of the dog population, where a high proportion of
      either stray or free-roaming dogs implies unrealistically high vaccination levels
      are required to prevent rabies. We find that the required control effort is less
      sensitive to continuous culling that increases the death rate of stray dogs than
      to changes in the carrying capacity of the stray dog population.

PMID- 28451587
TI  - The Interplay of Cofactor Interactions and Post-translational Modifications in
      the Regulation of the AAA+ ATPase p97.
AB  - The hexameric type II AAA ATPase (ATPase associated with various activities) p97
      (also referred to as VCP, Cdc48, and Ter94) is critically involved in a variety
      of cellular activities including pathways such as DNA replication and repair
      which both involve chromatin remodeling, and is a key player in various protein
      quality control pathways mediated by the ubiquitin proteasome system as well as
      autophagy. Correspondingly, p97 has been linked to various pathophysiological
      states including cancer, neurodegeneration, and premature aging. p97 encompasses
      an N-terminal domain, two highly conserved ATPase domains and an unstructured C
      terminal tail. This enzyme hydrolyzes ATP and utilizes the resulting energy to
      extract or disassemble protein targets modified with ubiquitin from stable
      protein assemblies, chromatin and membranes. p97 participates in highly diverse
      cellular processes and hence its activity is tightly controlled. This is achieved
      by multiple regulatory cofactors, which either associate with the N-terminal
      domain or interact with the extreme C-terminus via distinct binding elements and
      target p97 to specific cellular pathways, sometimes requiring the simultaneous
      association with more than one cofactor. Most cofactors are recruited to p97
      through conserved binding motifs/domains and assist in substrate recognition or
      processing by providing additional molecular properties. A tight control of p97
      cofactor specificity and diversity as well as the assembly of higher-order p97
      cofactor complexes is accomplished by various regulatory mechanisms, which
      include bipartite binding, binding site competition, changes in oligomeric
      assemblies, and nucleotide-induced conformational changes. Furthermore, post
      translational modifications (PTMs) like acetylation, palmitoylation,
      phosphorylation, SUMOylation, and ubiquitylation of p97 have been reported which
      further modulate its diverse molecular activities. In this review, we will
      describe the molecular basis of p97-cofactor specificity/diversity and will
      discuss how PTMs can modulate p97-cofactor interactions and affect the
      physiological and patho-physiological functions of p97.

PMID- 28451591
TI  - The Role of Reduced Left Ventricular, Systolic Blood Volumes in ST Segment
      Potentials Overlying Diseased Tissue of the Ischemic Heart.
AB  - Myocardial ischemia is the response of the heart to reduced coronary blood flow,
      leading to changes in ST segment potentials. ST segment depression is regarded as
      an indicator of nontransmural myocardial ischemia; however, not all nontransmural
      ischemia results in ST depression. This apparent discrepancy may be the result of
      many complex factors in cardiac response mechanisms to reduced blood flow. As a
      result, sophisticated computer models have emerged that have provided key
      insights into this complex phenomenon and the circumstances surrounding ST
      depression. Though these models have been able to produce ST depressions, many
      have neglected the effect of intracavitary blood volume, associated with
      different phases of the cardiac cycle. To explore the influence of the cardiac
      blood volume variability on epicardial potentials during nontransmural ischemia,
      we incorporated a thin, subendocardial ischemic zone geometry into an
      anatomically realistic, image-based ventricular model, and generated a finite
      element, static bidomain solution to determine the resulting epicardial surface
      potentials. It was first determined that, under baseline conditions (i.e.,
      expanded left ventricular volumes corresponding to diastole), a predictable ST
      depression developed over the ischemic region. Left ventricular volume was then
      incrementally reduced, while maintaining the size and general shape of the
      ischemic region, in order to reflect the systolic phase of the cardiac cycle. As
      blood volume geometries decreased, epicardial ST depression overlying the
      ischemic region first increased in surface area as blood volume was reduced and
      before dramatically reducing near 30% blood volume reduction - accentuating the
      role and importance of blood volume variation in computational models of
      ischemia.

PMID- 28451592
TI  - The Consortium for Electrocardiographic Imaging.
AB  - Electrocardiographic imaging (ECGI) has recently gained attention as a viable
      diagnostic tool for reconstructing cardiac electrical activity in normal hearts
      as well as in cardiac arrhythmias. However, progress has been limited by the lack
      of both standards and unbiased comparisons of approaches and techniques across
      the community, as well as the consequent difficulty of effective collaboration
      across research groups.. To address these limitations, we created the Consortium
      for Electrocardiographic Imaging (CEI), with the objective of facilitating
      collaboration across the research community in ECGI and creating standards for
      comparisons and reproducibility. Here we introduce CEI and describe its two main
      efforts, the creation of EDGAR, a public data repository, and the organization of
      three collaborative workgroups that address key components and applications in
      ECGI. Both EDGAR and the workgroups will facilitate the sharing of ideas, data
      and methods across the ECGI community and thus address the current lack of
      reproducibility, broad collaboration, and unbiased comparisons.

PMID- 28451590
TI  - Molecular Signaling of Progesterone, Growth Hormone, Wnt, and HER in Mammary
      Glands of Dogs, Rodents, and Humans: New Treatment Target Identification.
AB  - Mammary tumors are the most common form of neoplasia in the bitch. Female dogs
      are protected when they are spayed before the first estrus cycle, but this effect
      readily disappears and is already absent when dogs are spayed after the second
      heat. As the ovaries are removed during spaying, ovarian steroids are assumed to
      play an essential role in tumor development. The sensitivity toward tumor
      development is already present during early life, which may be caused by early
      mutations in stem cells during the first estrus cycles. Later on in life, tumors
      arise that are mostly steroid-receptor positive, although a small subset of
      tumors overexpressing human epidermal growth factor 2 (HER2) and some lacking
      estrogen receptor, progesterone receptor (PR), and HER2 (triple negative) are
      present, as is the situation in humans. Progesterone (P4), acting through PR, is
      the major steroid involved in outgrowth of mammary tissue. PRs are expressed in
      two forms, the progesterone receptor A (PRA) and progesterone receptor B (PRB)
      isoforms derived from splice variants from a single gene. The dog and the whole
      family of canids have only a functional PRA isoform, whereas the PRB isoform, if
      expressed at all, is devoid of intrinsic biological activity. In human breast
      cancer, overexpression of the PRA isoform is related to more aggressive
      carcinomas making the dog a unique model to study PRA-related mammary cancer.
      Administration of P4 to adult dogs results in local mammary expression of growth
      hormone (GH) and wing less-type mouse mammary tumor virus integration site family
      4 (Wnt4). Both proteins play a role in activation of mammary stem cells. In this
      review, we summarize what is known on P4, GH, and Wnt signaling in canine mammary
      cancer, how the family of HER receptors could interact with this signaling, and
      what this means for comparative and translational oncological aspects of human
      breast cancer development.

PMID- 28451593
TI  - Temporal Dilation of Animal Cardiac Recordings Registered to Human Torso
      Geometries.
AB  - Recordings of cardiac surface potentials from animal hearts can be mapped into
      human torso and used as source potentials for torso simulation. However,
      geometric registration of the heart can introduce changes in the effective
      conduction velocity due to change in relative positions of the recording sites.
      We developed a time dilation technique to ensure that adjusted cardiac potential
      recordings had physiological timing similar to human recordings after
      registration and corrected for conduction velocity. Temporal dilation was
      performed both linearly and nonlinearly using two scaling techniques that reflect
      either global or local deformations. Linear temporal dilation of canine
      epicardial potential recordings using global scaling could be used to generate
      electrograms physiologically similar to humans in terms of conduction velocity,
      activation recovery interval, total activation time, and activation maps.
      Epicardial potential mapping of such dilated canine recordings thus allows the
      investigation of human-like arrhythmias and other disease states that can not be
      readily induced or measured in humans.

PMID- 28451594
TI  - Novel Biomarker for Evaluating Ischemic Stress Using an Electrogram Derived Phase
      Space.
AB  - The underlying pathophysiology of ischemia is poorly understood, resulting in
      unreliable clinical diagnosis of this disease. This limited knowledge of
      underlying mechanisms suggested a data driven approach, which seeks to identify
      patterns in the ECG data that can be linked statistically to underlying behavior
      and conditions of ischemic tissue. Previous studies have suggested that an
      approach known as Laplacian eigenmaps (LE) can identify trajectories, or
      manifolds, that are sensitive to different spatiotemporal consequences of
      ischemic stress, and thus serve as potential clinically relevant biomarkers. We
      applied the LE approach to measured transmural potentials in several canine
      preparations, recorded during control and ischemic conditions, and discovered
      regions on an approximated QRS-derived manifold that were sensitive to ischemia.
      By identifying a vector pointing to ischemia-associated changes to the manifold
      and measuring the shift in trajectories along that vector during ischemia, which
      we denote as Mshift, it was possible to also pull that vector back into signal
      space and determine which electrodes were responsible for driving the observed
      changes in the manifold. We refer to the signal space change as the manifold
      differential (Mdiff). Both the Mdiff and Mshift metrics show a similar degree of
      sensitivity to ischemic changes as standard metrics applied during the ST segment
      in detecting ischemic regions. The new metrics also were able to distinguish
      between sub-types of ischemia. Thus our results indicate that it may be possible
      to use the Mshift and Mdiff metrics along with ST derived metrics to determine
      whether tissue within the myocardium is ischemic or not.

PMID- 28451595
TI  - Medial Patellofemoral Ligament Repair Versus Reconstruction for Recurrent
      Patellar Instability: Two-Year Results of an Algorithm-Based Approach.
AB  - BACKGROUND: Patellar instability remains a challenging problem for both the
      patient and surgeon. Medial patellofemoral ligament (MPFL) repair has
      historically had poor results, and due to this, there is currently a trend toward
      reconstruction. PURPOSE/HYPOTHESIS: This study was undertaken to investigate
      experience with repair versus reconstruction of the MPFL using a multifactorial
      treatment algorithm approach. Our hypothesis was that there will be no
      significant difference in outcome scores between patients in the MPFL repair and
      reconstruction groups. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS:
      A total of 24 patients with recurrent (>=2) lateral patellar dislocations were
      included. All had failed nonoperative treatment for more than 6 months, and all
      were observed for a minimum of 2 years. First, magnetic resonance imaging (MRI)
      was used to find the location of the MPFL tear. A tilt test was used to determine
      whether a lateral retinacular lengthening was required to allow the patella to
      have neutral tilt. If the MRI showed a tibial tubercle-trochlear groove (TT-TG)
      distance greater than 20 mm, a tibial tubercle osteotomy (TTO) was recommended.
      An MPFL reconstruction was performed if the entire ligament was inadequately
      visualized on MRI or if it was torn from both insertion sites. Failure was
      defined as recurrent lateral patellar instability after surgery. As a secondary
      outcome measure, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm
      score, and Tegner score were calculated. RESULTS: All patients were evaluated
      with a mean follow-up of 51 months (range, 25-79 months). Sixteen patients
      initially underwent MPFL repair, 8 underwent reconstruction, and 3 also underwent
      TTO. MPFL reconstructions were performed in all patients who underwent TTO. One
      MPFL repair was to the anatomic femoral origin and 15 were to the patellar
      insertion corresponding to the site of tearing on MRI. A lateral retinacular
      lengthening was performed in 21 patients. There was 1 failure in the repair group
      (6%) and none in the reconstruction group. However, the patient who failed had a
      TT-TG distance of 26 mm but refused a TTO. She subsequently underwent revision
      with a TTO and MPFL reconstruction and did not have any further instability
      events. There were no significant differences between groups for any of the
      secondary outcome scores. CONCLUSION: Using an algorithm-based approach, MPFL
      repair or reconstruction may lead to clinically acceptable results at 2-year
      follow-up.

PMID- 28451596
TI  - How Comprehensive and Efficient Are Patient-Reported Outcomes for Rotator Cuff
      Tears?
AB  - BACKGROUND: Increasing emphasis is placed on patient-reported outcomes (PROs)
      after common orthopaedic procedures as a measure of quality. When considering PRO
      utilization in patients with rotator cuff tears, several different PROs exist
      with varying levels of accuracy and utilization. HYPOTHESIS/PURPOSE:
      Understanding which disease-specific PRO may be most efficiently administered in
      patients after rotator cuff repair may assist in promoting increased patient and
      physician adoption of these useful scores. Using a novel assessment criterion,
      this study assessed all commonly used rotator cuff PROs. We hypothesize that
      surveys with fewer numbers of questions may remain comparable (with regard to
      comprehensiveness) to longer surveys. STUDY DESIGN: Systematic review. METHODS:
      Commonly utilized rotator cuff PROs were analyzed with regard to number of survey
      components, comprehensiveness, and efficiency. Comprehensiveness (maximum score,
      11) was scored as the total number of pain (at rest/baseline, night/sleep,
      activities of daily living [ADLs], sport, and work) and functional (strength,
      motion/stiffness, and ability to perform ADLs, sport, and work) metrics included,
      along with inclusion of quality of life/satisfaction metrics. Efficiency was
      calculated as comprehensiveness divided by the number of survey components.
      RESULTS: Sixteen different PROs were studied. Number of components ranged from 5
      (University of California at Los Angeles score [UCLA]) to 36 (Short Form-36 [SF
      36], Japanese Orthopaedic Association score [JOA]). The Quality of Life Outcome
      Measure for Rotator Cuff Disease (RC-QoL) included all 5 pain components, while 7
      PROs contained all 5 functional components. Ten PROs included a quality of
      life/satisfaction component. The most comprehensive scores were the RC-QoL
      (score, 11) and Penn (score, 10), and the least comprehensive score was the Marx
      (score, 3). The most efficient PROs were the UCLA, the Quick Disabilities of the
      Arm, Shoulder, and Hand score (QuickDASH), and Constant scores. The least
      efficient scores were the JOA and SF-36 scores. CONCLUSION: Many commonly
      utilized PROs for rotator cuff tears are lacking in comprehensiveness and
      efficiency. Continued critical assessment of PRO quality may help practitioners
      identify the most comprehensive and efficient PRO to incorporate into daily
      clinical practice.

PMID- 28451597
TI  - Outcomes and Complications After All-Epiphyseal Anterior Cruciate Ligament
      Reconstruction in Skeletally Immature Patients.
AB  - BACKGROUND: The safest and most effective technique for anterior cruciate
      ligament (ACL) reconstruction in skeletally immature patients is currently
      unknown. PURPOSE: To evaluate the functional and patient-reported outcomes of a
      specific all-epiphyseal ACL reconstruction technique in which the graft, bone
      tunnels, and fixation do not cross the knee growth plates. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Twenty-seven patients (23 boys, 4 girls;
      mean age, 11 years; range, 8-15 years) underwent an all-epiphyseal ACL
      reconstruction with a single femoral transverse epiphyseal tunnel and primarily
      split tibial epiphyseal tunnels. Outcomes were evaluated in terms of the manual
      Lachman test, range of motion, pain, return to activity, angular or leg-length
      deformity on imaging, and International Knee Documentation Committee (IKDC) or
      Pedi-IKDC score an average of 3.8 years postoperatively, with a minimum 2-year
      follow-up. RESULTS: The mean IKDC score was 94 +/- 11. There were no growth
      arrests, but 3 patients had knee overgrowth, and 2 required a subsequent guided
      growth procedure. The ACL graft failed in 4 patients (15%), and 2 patients had
      contralateral ACL tears (7%). There were 5 subsequent ipsilateral meniscal tears,
      4 of which were retears of a repaired meniscus. Ipsilateral knee reinjury
      significantly correlated with the number of associated injuries at the time of
      index surgery (P = .040) and the number of sports played (P = .029). CONCLUSION:
      All-epiphyseal ACL reconstruction resulted in excellent long-term functional
      outcomes, despite a high rate of complications (48%) and secondary procedures
      (37%) in this highly active cohort. The incidence of graft failure was similar to
      other standard ACL reconstruction techniques for patients younger than 20 years.

PMID- 28451598
TI  - Epidemiology and Impact of Abdominal Oblique Injuries in Major and Minor League
      Baseball.
AB  - BACKGROUND: Oblique injuries are known to be a common cause of time out of play
      for professional baseball players, and prior work has suggested that injury rates
      may be on the rise in Major League Baseball (MLB). PURPOSE: To better understand
      the current incidence of oblique injuries, determine their impact based on time
      out of play, and to identify common injury patterns that may guide future injury
      prevention programs. STUDY DESIGN: Descriptive epidemiological study. METHODS:
      Using the MLB Health and Injury Tracking System, all oblique injuries that
      resulted in time out of play in MLB and Minor League Baseball (MiLB) during the
      2011 to 2015 seasons were identified. Player demographics such as age,
      position/role, and handedness were included. Injury-specific factors analyzed
      included the following: date of injury, timing during season, days missed,
      mechanism, side, treatment, and reinjury status. RESULTS: A total of 996 oblique
      injuries occurred in 259 (26%) MLB and 737 (74%) MiLB players. Although the
      injury rate was steady in MiLB, the MLB injury rate declined (P = .037). A total
      of 22,064 days were missed at a mean rate of 4413 days per season and 22.2 days
      per injury. The majority of these occurred during batting (n = 455, 46%) or
      pitching (n = 348, 35%), with pitchers losing 5 days more per injury than batters
      (P < .001). The leading side was injured in 77% of cases and took 5 days longer
      to recover from than trailing side injuries (P = .009). Seventy-nine (7.9%)
      players received either a corticosteroid or platelet-rich plasma injection, and
      the mean recovery time was 11 days longer compared with those who did not receive
      an injection (P < .001). CONCLUSION: Although the rate of abdominal oblique
      injuries is on the decline in MLB, this is not the case for MiLB, and these
      injuries continue to represent a significant source of time out of play in
      professional baseball. The vast majority of injuries occur on the lead side, and
      these injuries result in the greatest amount time out of play. The benefit of
      injections for the treatment of oblique injuries remains unknown.

PMID- 28451600
TI  - Current Concepts in the Diagnosis and Management of Traumatic, Anterior
      Glenohumeral Subluxations.
AB  - Traumatic anterior glenohumeral subluxations comprise the majority of
      glenohumeral instability events and are endemic in young athletes. Unlike the
      definitive complete dislocation event, subluxation events may often be more
      subtle in presentation and, therefore, may be overlooked by clinicians.
      Glenohumeral subluxation events are associated with a high rate of labral tears
      as well as humeral head defects. While less is known of the natural history of
      these injuries, young athletes are at risk for recurrent instability events if
      not properly diagnosed and treated. While reports of surgical treatment outcomes
      isolated to subluxation events are limited, arthroscopic and open Bankart repair
      have been shown to result in excellent outcomes. The purpose of this paper is to
      review the etiology and pathoanatomy of traumatic anterior glenohumeral
      subluxations as well as to review the appropriate evaluation and management of
      patients with this injury.

PMID- 28451599
TI  - Is Home-Based, High-Intensity Interval Training Cycling Feasible and Safe for
      Patients With Knee Osteoarthritis?: Study Protocol for a Randomized Pilot Study.
AB  - BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease affecting the
      knee joint of many middle-aged and older adults. As OA symptoms typically involve
      knee pain and stiffness, individuals with knee OA are often insufficiently
      physically active, have low levels of physical function, and are at increased
      risk of other comorbidities and reduced quality of life. While moderate-intensity
      continuous training (MICT) cycling is often recommended, little is known about
      the feasibility, safety, and benefits of high-intensity interval training (HIIT)
      cycling for this population, even though the feasibility, safety, and benefits of
      HIIT have been demonstrated in other chronic disease groups. PURPOSE: The primary
      objective of this pilot study was to examine the feasibility and safety of home
      based HIIT and MICT cycling in middle-aged and older adults with knee OA. A
      secondary objective was to gain some insight into the relative efficacy of HIIT
      and MICT for improving health status (pain, stiffness, and disability), muscle
      function, and body composition in this population. This study protocol is being
      published separately to allow a detailed description of the research methods,
      explain the rationale for choosing the methodological details, and to stimulate
      consideration of the best means to simulate a research protocol that is relevant
      to a real-life treatment environment. STUDY DESIGN: Randomized pilot study
      protocol. METHODS: This trial sought to recruit 40 middle-aged and older adults
      with knee OA. Participants were randomly allocated to either continuous (MICT) or
      HIIT home-based cycle training programs, with both programs requiring the
      performance of 4 cycling sessions (approximately 25 minutes per session) each
      week. Participants were measured at baseline and postintervention (8 weeks).
      Feasibility and safety were assessed by adherence rate, dropout rate, and number
      of adverse events. The relative efficacy of the cycling programs was investigated
      by 2 knee OA health status questionnaires (Western Ontario and McMaster
      Universities Osteoarthritis Index scale[WOMAC] and the Lequesne Index) as well as
      the timed up and go, sit to stand, preferred gait speed, and body composition.
      DISCUSSION: This pilot study appears to be the first study assessing the
      feasibility and safety of a home-based HIIT training program for middle-aged and
      older adults with knee OA. As HIIT has been demonstrated to be more effective
      than MICT for improving aspects of health status, body composition, and/or
      muscular function in other chronic disease groups, the current study has the
      potential to improve patient outcomes and inform the design of future randomized
      controlled trials.

PMID- 28451601
TI  - Cost Comparison of Outpatient Versus Inpatient Unicompartmental Knee
      Arthroplasty.
AB  - BACKGROUND: Outpatient unicompartmental knee arthroplasty (UKA) has been shown to
      be safe and feasible when compared with inpatient surgery; however, no studies
      have evaluated the cost-effectiveness and cost-benefit of performing outpatient
      versus inpatient UKA. HYPOTHESIS: Significant cost savings can be achieved by
      transitioning UKAs from an inpatient to an outpatient procedure in an outpatient
      surgical facility, with no appreciable difference in complication or readmission
      rates. STUDY DESIGN: Economic and decision analysis; Level of evidence, 3.
      METHODS: A retrospective chart review of 25 consecutive medial UKAs was
      performed. A total of 10 inpatient UKAs with a mean length of stay of 1.6 days
      (range, 1-4 days) and 12 outpatient UKAs were included in the final analysis. A
      simple difference in costs incurred, reimbursements, and percentage difference
      between inpatient and outpatient surgery in an outpatient surgical facility was
      calculated. Charges were subdivided into surgical facility fees, inpatient room
      charges, operating room supply fees, and other fees. Secondary outcome measures
      included reason for greater than 1 day stay for the inpatient UKAs,
      complications, readmissions, and the type of regional anesthesia utilized.
      RESULTS: The outpatient UKA charges were a mean $20,500 less per patient than the
      inpatient average charge of $46,845. The primary cost savings were attributed to
      the outpatient surgical facility fee, which averaged $3800 per patient, while the
      inpatient facility charge was 350% more expensive at $13,200 per patient
      (approximately $9500 savings). On the inpatient side, the average reimbursement
      was 55% of charges, or $25,550. For outpatient procedures, the average
      reimbursement was 47%, or $12,370. There was no difference between the inpatient
      and outpatient groups in terms of complications or readmissions. CONCLUSION: This
      work demonstrated that significant cost savings of roughly 50% can be achieved
      with an outpatient UKA protocol done at an outpatient surgical facility. Not only
      is it feasible and economically attractive to perform outpatient UKA, but it can
      reduce inpatient bed occupancy and resource allocation for a busy hospital.

PMID- 28451602
TI  - Exceeding Pitch Count Recommendations in Little League Baseball Increases the
      Chance of Requiring Tommy John Surgery as a Professional Baseball Pitcher.
AB  - BACKGROUND: Empirical evidence has suggested a connection between youth pitch
      counts and subsequent elbow injury. For players within the Little League World
      Series (LLWS), detailed historical player data are available. Some of these
      players progress to both professional play and require an ulnar collateral
      ligament reconstruction (UCLR). PURPOSE: To determine the percentage of LLWS
      pitchers who proceed to play professional (major or minor league) baseball, the
      rate of UCLR in former LLWS pitchers who played professional baseball, and the
      risk to those who exceeded current pitch count recommendations while playing in
      the LLWS. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All LLWS
      pitchers from 2001 through 2009 from all teams and countries were identified, and
      all performance data were extracted. A professional (major and minor league)
      baseball database was then searched to determine whether each former LLWS pitcher
      played professional baseball. These professional players were then searched for
      using publicly available databases to determine whether they underwent UCLR.
      RESULTS: Overall, 638 adolescents pitched in the LLWS between 2001 and 2009; 62
      (10%) progressed to professional play. Of the 56 minor league players, 25 (45%)
      pitched. Of the 6 Major League Baseball players, 3 (50%) pitched. Three former
      LLWS pitchers (5%) who played professionally underwent UCLR. In former LLWS
      pitchers who exceeded pitch counts and played professionally, 50% (2/4) required
      UCLR, while only 1.7% (1/58) of those who did not exceed pitch count
      recommendations required UCLR (P = .009). Similarly, among former LLWS pitchers
      who subsequently played professionally, 23.1% of those who played as a pitcher
      required UCLR while 0% of those who also played other positions required UCLR (P
      = .008). CONCLUSION: Progression from LLWS pitching to professional baseball is
      uncommon. Among youth players, both diversification (playing other positions
      besides pitcher) as well as following current pitch limit regulations may protect
      against UCLR.

PMID- 28451603
TI  - Balance Markers in Adolescents at 1 Month Postconcussion.
AB  - BACKGROUND: The Balance Error Scoring System (BESS) shows that balance tends to
      recover within days after a concussion, whereas measures of the movement of the
      center of pressure (COP) show that balance deficits can persist up to 1 month
      after concussion. While approximately 30% of adolescents suffering concussion
      have functional consequences including balance deficits, evidence of the use of
      different balance assessments for concussion is limited within this population.
      PURPOSE: To compare performance on a series of balance assessments between
      adolescents with a diagnosed concussion at 1 month postinjury and noninjured
      control participants within the same age distribution. STUDY DESIGN: Cross
      sectional study; Level of evidence, 3. METHODS: Thirty-three adolescents 1 month
      postconcussion and 33 control participants completed the BESS followed by two, 2
      minute trials standing on a Nintendo Wii Balance Board (WBB), during which the
      COP under their feet was recorded using 2 testing protocols: (1) double-leg
      stance, eyes open (EO) and (2) double-leg stance, eyes closed (EC). Participants
      then completed a dual-task condition (DT) with eyes open combining a double-leg
      stance and a Stroop color and word test while standing on the WBB. Three commonly
      used COP variables, anterior-posterior (A/P) and mediolateral (M/L) velocity and
      95% ellipse, were computed for each condition performed on the WBB. RESULTS:
      Participants postconcussion swayed over a significantly larger ellipse area
      compared with the control group in the EO (P = .008), EC (P = .002), and DT (P =
      .003) conditions and also performed the DT condition with faster COP velocity in
      the M/L direction (P = .007). No significant group difference was identified for
      BESS total score. CONCLUSION: At 1 month postconcussion, participants continued
      to demonstrate balance deficits in COP control despite scoring similar to
      controls on the BESS. Simple COP measures of balance may identify subtle
      impairments not captured by the BESS.

PMID- 28451604
TI  - Open Reduction Internal Fixation of Isolated Chondral Fragments Without Osseous
      Attachment in the Knee: A Case Series.
AB  - BACKGROUND: Isolated chondral fractures of the knee are a rare and challenging
      problem, typically occurring with an acute traumatic event such as dislocation of
      the patella or ligamentous injury. Historically, repair of unstable chondral
      fragments without osseous attachment has not been recommended due to concerns
      about the limited healing potential of cartilage. PURPOSE: To describe a
      technique for fixation of large isolated chondral fractures of the knee and
      present 3 cases where large chondral fragments without osseous attachment were
      fixed successfully with chondral darts and biologic adhesive. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: The senior author reviewed his case logs
      for all patients on whom he performed open reduction and internal fixation on
      large isolated cartilage fragments without osseous attachment. Three were
      extracted from his review. The clinical and radiographic outcomes were
      retrospectively reviewed. RESULTS: Successful results and complete healing was
      obtained in all 3 patients. This procedure can be done in the setting of
      concurrent injury, such as anterior cruciate ligament tear, using single- or
      multistaged chondral repair and ligament reconstruction techniques. CONCLUSION:
      Isolated chondral fragment repair techniques provide the orthopaedic surgeon an
      additional option for treating these challenging injuries. Primary fixation can
      be accomplished for what have been historically considered "unsalvageable"
      fragments.

PMID- 28451606
TI  - Ultrasound and Functional Assessment of Transtendinous Repairs of Partial
      Thickness Articular-Sided Rotator Cuff Tears.
AB  - BACKGROUND: Partial-thickness articular-sided rotator cuff tears are a frequent
      source of shoulder pain. Despite conservative measures, some patients continue to
      be symptomatic and require surgical management. However, there is some
      controversy as to which surgical approach results in the best outcomes for grade
      3 tears. HYPOTHESIS/PURPOSE: The purpose of this study was to evaluate repair
      integrity and the clinical results of patients treated with transtendinous repair
      of high-grade partial-thickness articular-sided rotator cuff tears. Our
      hypothesis was that transtendinous repairs would result in reliable healing and
      acceptable functional outcomes. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Twenty patients with a minimum follow-up of 2 years were included in the
      study. All patients underwent arthroscopic repair of high-grade partial-thickness
      rotator cuff tears utilizing a transtendinous technique by a single surgeon. At
      latest follow-up, the repair integrity was evaluated using ultrasound imaging,
      and functional scores were calculated. RESULTS: Ultrasound evaluation
      demonstrated that 18 of 20 patients had complete healing with a normal-appearing
      rotator cuff. Two patients had a minor residual partial tear. Sixteen of 20
      patients had no pain on visual analog scale. Four patients complained of mild
      intermittent residual pain. All patients were rated as "excellent" by both the
      University of California at Los Angeles Shoulder Score and the Simple Shoulder
      Test. CONCLUSION: The transtendon technique for the repair of articular-sided
      high-grade partial rotator cuff tears results in reliable tendon healing and
      excellent functional outcomes.

PMID- 28451605
TI  - The Impact of Osseous Malalignment and Realignment Procedures in Knee Ligament
      Surgery: A Systematic Review of the Clinical Evidence.
AB  - BACKGROUND: Failure rates of knee ligament surgery may be high, and the impact of
      osseous alignment on surgical outcome remains controversial. Basic science
      studies have demonstrated that osseous malalignment can negatively affect
      ligament strain and that realignment procedures may improve knee joint stability.
      HYPOTHESIS/PURPOSE: The purpose of this review was to summarize the clinical
      evidence concerning the impact of osseous malalignment and realignment procedures
      in knee ligament surgery. The hypotheses were that lower extremity malalignment
      would be an important contributor to knee ligament surgery failure and that
      realignment surgery would contribute to increased knee stability and improved
      outcome in select cases. STUDY DESIGN: Systematic review; Level of evidence, 4.
      METHODS: According to the PRISMA (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses) guidelines, a systematic electronic search of the
      PubMed database was performed in November 2015 to identify clinical studies
      investigating (A) the influence of osseous alignment on postoperative stability
      and/or failure rates after knee ligament surgery and (B) the impact of osseous
      realignment procedures in unstable knees with or without additional knee ligament
      surgery on postoperative knee function and stability. Methodological quality of
      the studies was assessed using the Oxford Centre for Evidence-Based Medicine
      Levels of Evidence and the Coleman Methodological Score (CMS). RESULTS: Of the
      1466 potentially relevant articles, 28 studies fulfilled the inclusion and
      exclusion criteria. Average study quality was poor (CMS, 40). For part A, studies
      showed increased rerupture rate after anterior cruciate ligament (ACL)
      replacement in patients with increased tibial slope. Concerning the posterior
      cruciate ligament (PCL)/posterolateral corner (PLC)/lateral collateral ligament
      (LCL), varus malalignment was considered a significant risk factor for failure.
      For part B, studies showed decreased anterior tibial translation after slope
      decreasing high tibial osteotomy in ACL-deficient knees. Correcting varus
      malalignment in PCL/PLC/LCL instability also showed increased stability and
      better outcomes. CONCLUSION: In cases of complex knee instability, the 3
      dimensional osseous alignment of the knee should be considered (eg, mechanical
      weightbearing line and tibial slope). In cases of failed ACL reconstruction, the
      tibial slope should be considered, and slope-reducing osteotomies are often
      helpful in the patient revised multiple times. In cases of chronic PCL and/or PLC
      instability, osseous correction of the varus alignment may reduce the failure
      rate and is often the first step in treatment. Changes in the mechanical axis
      should be considered in all cases of instability accompanied by early
      unicompartmental osteoarthritis.

PMID- 28451607
TI  - Outcomes After Arthroscopic Bankart Repair in Adolescent Athletes Participating
      in Collision and Contact Sports.
AB  - BACKGROUND: Literature on arthroscopic stabilization in adolescent patients
      participating in collision and contact sports is limited, as most studies include
      adolescents within a larger sample group comprised primarily of adults. PURPOSE:
      To review the outcomes of arthroscopic Bankart repair for anterior shoulder
      instability in an adolescent population participating in collision and contact
      sports. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This
      retrospective review included 39 shoulders in 37 adolescent (<=19 years) athletes
      who underwent primary arthroscopic Bankart repair using suture anchors with at
      least 2-year follow-up. All patients had a history of trauma to their shoulder
      resulting in an anterior dislocation. Outcome measures included patient
      satisfaction, the visual analog scale (VAS) for pain, American Shoulder and Elbow
      Surgeons (ASES) score, and Rowe score. Recurrence of dislocation and return to
      sporting activity were also assessed. RESULTS: The mean age at the time of
      surgery was 16.9 years (range, 15-19 years), and the mean follow-up was 6.3 years
      (range, 4.3-10.0 years); 58.6% of patients participated in collision sports. Time
      to surgery after the initial dislocation episode was 9.2 months (range, 0.5-36.2
      months). Four shoulders (10.3%) had dislocation events postoperatively. The
      majority (78.1%) of patients returned to sports at the same level of competition.
      Mean VAS was 0.49 +/- 1.0, and the mean ASES and Rowe scores were 92.8 +/- 12.6
      and 85.0 +/- 24.2, respectively. Univariate analyses demonstrated that subjective
      functional outcomes were negatively correlated with recurrence (ASES, P = .005;
      Rowe, P = .001) and failure to return to sport (ASES, P = .016; Rowe, P = .004).
      Independent variables shown to have no significant relationship to functional
      outcomes included age, follow-up, number of preoperative dislocations, time to
      surgery, sport classification, competition level, tear extent, number of anchors,
      concurrent Hill-Sachs lesion, and repair of a superior labral anterior-posterior
      (SLAP) lesion. CONCLUSION: Arthroscopic Bankart repair is an effective surgical
      option for traumatic shoulder instability in adolescents participating in
      collision and contact sports. At a minimum 4-year follow-up, arthroscopic Bankart
      repair effectively restored stability in 90% of cases; 80% returned to their
      preinjury level of sport.

PMID- 28451608
TI  - The Functional Arm Scale for Throwers (FAST)-Part I: The Design and Development
      of an Upper Extremity Region-Specific and Population-Specific Patient-Reported
      Outcome Scale for Throwing Athletes.
AB  - BACKGROUND: Upper extremity (UE) region-specific, patient-reported outcome (PRO)
      scales assess injuries to the UE but do not account for the demands of overhead
      throwing athletes or measure patient-oriented domains of health-related quality
      of life (HRQOL). PURPOSE: To develop the Functional Arm Scale for Throwers
      (FAST), a UE region-specific and population-specific PRO scale that assesses
      multiple domains of disablement in throwing athletes with UE injuries. In stage
      I, a beta version of the scale was developed for subsequent factor
      identification, final item reduction, and construct validity analysis during
      stage II. STUDY DESIGN: Descriptive laboratory study. METHODS: Three-stage scale
      development was utilized: Stage I (item generation and initial item reduction)
      and stage II (factor analysis, final item reduction, and construct validity) are
      reported herein, and stage III (establishment of measurement properties
      [reliability and validity]) will be reported in a companion paper. In stage I, a
      beta version was developed, incorporating National Center for Medical
      Rehabilitation Research disablement domains and ensuring a blend of sport-related
      and non-sport-related items. An expert panel and focus group assessed importance
      and interpretability of each item. During stage II, the FAST was reduced,
      preserving variance characteristics and factor structure of the beta version and
      construct validity of the final FAST scale. RESULTS: During stage I, a 54-item
      beta version and a separate 9-item pitcher module were developed. During stage
      II, a 22-item FAST and 9-item pitcher module were finalized. The factor solution
      for FAST scale items included pain (n = 6), throwing (n = 10), activities of
      daily living (n = 5), psychological impact (n = 4), and advancement (n = 3). The
      6-item pain subscale crossed factors. The remaining subscales and pitcher module
      are distinctive, correlated, and internally consistent and may be interpreted
      individually or combined. CONCLUSION: This article describes the development of
      the FAST, which assesses clinical outcomes and HRQOL of throwing athletes after
      UE injury. The FAST encompasses multiple domains of disability and demonstrates
      excellent construct validity. CLINICAL RELEVANCE: The FAST provides a single UE
      region-specific and population-specific PRO scale for high-demand throwers to
      facilitate measurement of impact of UE injuries on HRQOL and clinical outcomes
      while quantifying recovery for comparative effectiveness studies.

PMID- 28451609
TI  - The Pediatric/Adolescent Shoulder Survey (PASS): A Reliable Youth Questionnaire
      With Discriminant Validity and Responsiveness to Change.
AB  - BACKGROUND: Health-related quality of life tools for shoulder pathology in adults
      have been developed, such as the Disabilities of the Arm, Shoulder, and Hand
      (DASH) or QuickDASH. However, some content is not applicable to or readily
      grasped by a younger population. PURPOSE: To evaluate the psychometric properties
      of a new 13-item pediatric/adolescent shoulder survey (PASS). STUDY DESIGN:
      Cohort study (diagnosis); Level of evidence, 2. METHODS: An initial development
      cohort of children was given the PASS, QuickDASH, and single assessment numeric
      evaluation (SANE) in a prospective fashion. Internal reliability and concurrent
      validity were evaluated. Subsequent to this, the PASS, along with the QuickDASH,
      was incorporated into routine clinical evaluation of shoulder injuries. The
      secondary cohort was established via a retrospective review of patients (age <18
      years) evaluated in our sports clinics for shoulder complaints. Discriminant
      validity and floor/ceiling effects were evaluated. A subset of patients with
      scores available both pre- and within 6 months postoperatively was analyzed to
      assess responsiveness to treatment. RESULTS: Overall internal reliability of the
      shoulder survey was good in the development cohort of 127 patients, with Cronbach
      alpha = 0.86. Total score averaged 59.7% +/- 17.9% in this cohort (range, 18.75%
      100%). Significant correlations between all surveys were observed (r = 0.51-0.79,
      P < .05). A total of 127 surveys were available for the secondary cohort. The
      QuickDASH demonstrated significant differences between sexes with regard to
      scores (P < .05). Both tools were able to discriminate between patients with
      acute injuries and diminished clinical examinations (P < .05). A significant
      correlation was observed between duration of symptoms and scores on the PASS. The
      subset of 25 patients with pre- and postoperative data showed significant change
      in total score and the symptoms/limitations domain of the PASS, with significant
      correlation with length of time since surgery. CONCLUSION: This 13-question
      pediatric/adolescent-focused shoulder survey shows excellent psychometric
      properties, good discriminant ability, and early evidence of responsiveness to
      change, especially when compared with an adult-formatted questionnaire.

PMID- 28451610
TI  - Changes Within Clinical Practice After a Randomized Controlled Trial of Knee
      Arthroscopy for Osteoarthritis.
AB  - BACKGROUND: In 2002, Moseley et al published a randomized controlled trial (RCT)
      that showed no difference between knee arthroscopy and placebo for patients with
      osteoarthritis (OA). We wanted to assess the impact of the trial on clinical
      practice in the United States. PURPOSE/HYPOTHESIS: To evaluate changes in knee
      arthroscopy practice before and after publication of the article by Moseley et al
      and to assess the effect of this landmark RCT on the behavior of practicing
      orthopaedic surgeons. We hypothesized that after publication of the Moseley
      trial, the overall frequency of knee arthroscopy would decrease, that the mean
      age of patients undergoing knee arthroscopy would decrease, and that the
      proportion of arthroscopies for a diagnosis of OA would decrease. STUDY DESIGN:
      Descriptive epidemiology study. METHODS: The State Ambulatory Surgery Database
      was used to analyze cases from 1998 to 2006, which were classified as meniscus
      tear, OA, or OA with meniscus tear. Changes in age, surgery rates, and case
      classification were evaluated before and after Moseley's trial using Student t
      tests and analysis of variance. RESULTS: After publication of the trial, the
      number of knee arthroscopies per year increased from 155,057 in 1998 to 172,317
      in 2006 (P <= .001). Mean patient age increased from 47.6 to 49.2 years (P <
      .001). Meniscus tears increased from 69.1% to 70.8%, representing approximately
      15,500 additional cases per year. OA decreased from 10.6% to 7.2%, representing
      approximately 4000 fewer cases per year. OA with meniscus tear increased from
      20.3% to 22.0%, representing approximately 6400 additional cases per year.
      CONCLUSION: While overall age and rates of knee arthroscopy increased contrary to
      our hypothesis, we identified a decrease in rates of knee arthroscopy for OA
      after publication of the Moseley trial, demonstrating that well-publicized RCTs
      can influence patterns of clinical practice.

PMID- 28451611
TI  - Return to Play After Revision Anterior Cruciate Ligament Reconstruction in
      National Football League Players.
AB  - BACKGROUND: National Football League (NFL) players who undergo anterior cruciate
      ligament (ACL) reconstruction have been shown to have a lower return to play
      (RTP) than previously expected. However, RTP in the NFL after revision ACL
      reconstruction (RACLR) is not well defined. PURPOSE/HYPOTHESIS: The purpose of
      this study is to determine the RTP of NFL players after RACLR and evaluate
      factors that predict RTP. Our hypothesis was that more experienced and
      established players would be more likely to RTP after RACLR. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: A total of 24 NFL players who underwent
      RACLR between 2007 and 2014 were reviewed and evaluated. Return to NFL play, time
      to return, seasons and games played prior to and after revision surgery, draft
      status, and demographic data were collected. Overall RTP was determined, and
      players who did RTP were compared with those unable to RTP. Data were also
      compared with control players matched for age, position, size, and experience.
      RESULTS: After RACLR, 79% (19/24) of NFL players returned to NFL regular-season
      play at an average of 12.6 months. All players who were drafted in the first 4
      rounds, played in at least 55 games, or played 4 seasons of NFL play prior to
      injury were able to RTP. Players drafted in the first 4 rounds of the NFL draft
      were more likely to RTP than those who were not (odds ratio, 0.1; 95% CI, 0.01
      1.00; P = .05). Those who returned to NFL play played in significantly less games
      and seasons after their injury than before (P = .01 and P = .01, respectively).
      However, these values did not differ when compared with matched controls (P = .67
      and P = .33). CONCLUSION: NFL players who RTP after RACLR do so at a similar rate
      but prolonged time period compared with after primary ACL reconstruction.
      Athletes who were drafted in earlier rounds were more likely to RTP than those
      who were not. Additionally, player experience prior to injury is an important
      factor when predicting RTP after RACLR.

PMID- 28451612
TI  - Performance and Return to Sport After Sports Hernia Surgery in NFL Players.
AB  - BACKGROUND: Recognition, diagnosis, and treatment of athletic pubalgia (AP), also
      known as sports hernia, once underrecognized and undertreated in professional
      football, are becoming more common. Surgery as the final treatment for sports
      hernia when nonsurgical treatment fails remains controversial. Given the money
      involved and popularity of the National Football League (NFL), it is important to
      understand surgical outcomes in this patient population. HYPOTHESIS: After AP
      surgery, players would: (1) return to sport (RTS) at a greater than 90% rate, (2)
      play fewer games for fewer years than matched controls, (3) have no difference in
      performance compared with before AP surgery, and (4) have no difference in
      performance versus matched controls. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: Internet-based injury reports identified players who
      underwent AP surgery from January 1996 to August 2015. Demographic and
      performance data were collected for each player. A 1:1 matched control group and
      an index year analog were identified. Control and case performance scores were
      calculated using a standardized scoring system. Groups were compared using paired
      Student t tests. RESULTS: Fifty-six NFL players (57 AP surgeries) were analyzed
      (mean age, 28.2 +/- 3.1 years; mean years in NFL at surgery, 5.4 +/- 3.2). Fifty
      three players were able to RTS. Controls were in the NFL longer (P < .05) than
      players who underwent AP surgery (3.8 +/- 2.4 vs 3.2 +/- 2.1 years). Controls
      played more games per season (P < .05) than post-AP players (14.0 +/- 2.3 vs 12.0
      +/- 3.4 games per season). There was no significant (P > .05) difference in pre-
      versus post-AP surgery performance scores and no significant (P > .05) difference
      in postoperative performance scores versus controls post-index. CONCLUSION: There
      was a high RTS rate after AP surgery without a significant difference in
      postoperative performance, though career length and games per season after AP
      surgery were significantly less than that of matched controls.

PMID- 28451613
TI  - Medial Patellar Instability: Treatment and Outcomes.
AB  - BACKGROUND: Historically, a lateral retinacular release was one of the primary
      surgical interventions used to treat lateral patellar instability. However,
      disruption of the lateral structures during this procedure has been associated
      with medial instability of the patella. HYPOTHESIS: We hypothesize that good to
      excellent outcomes can be achieved at midterm follow-up after lateral
      patellotibial ligament reconstruction. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Thirteen patients were treated for medial patellar
      instability with a lateral patellotibial ligament reconstruction between May 2011
      and December 2013 by a single surgeon. All patients had previously undergone a
      lateral release procedure and had symptomatic medial patellar instability.
      Patients were evaluated using patient-reported outcome scores at a minimum of 2
      years postsurgery. RESULTS: The mean Lysholm score improved from 45.6 (range, 11
      76) to 71.9 (range, 30-91). The median preoperative Tegner activity scale score
      was 3 (range, 1-7), while the median postoperative score was 4 (range, 1-9). The
      median Western Ontario and McMaster Universities Arthritis Index (WOMAC) total
      score improved from 38 (range, 1-57) preoperatively to 6 postoperatively (range,
      0-52). The mean patient satisfaction postoperatively was 8.2 (range, 5-10).
      CONCLUSION: Significantly improved outcomes can be achieved at midterm follow-up
      with a low rate of complications when reconstructing the lateral patellotibial
      ligament in the setting of iatrogenic medial patellar instability.

PMID- 28451614
TI  - The Functional Arm Scale for Throwers (FAST)-Part II: Reliability and Validity of
      an Upper Extremity Region-Specific and Population-Specific Patient-Reported
      Outcome Scale for Throwing Athletes.
AB  - BACKGROUND: The Functional Arm Scale for Throwers (FAST) is an upper extremity
      (UE) region-specific and population-specific patient-reported outcome (PRO) scale
      developed to measure health-related quality of life in throwers with UE injuries.
      Stages I and II, described in a companion paper, of FAST development produced a
      22-item scale and a 9-item pitcher module. Stage III of scale development,
      establishing reliability and validity of the FAST, is reported herein. PURPOSE:
      To describe stage III of scale development: reliability and validity of the FAST.
      STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Data from
      throwing athletes collected over 5 studies were pooled to assess reliability and
      validity of the FAST. Reliability was estimated using FAST scores from 162
      throwing athletes who were injured (n = 23) and uninjured (n = 139). Concurrent
      validity was estimated using FAST scores and Disabilities of the Arm, Shoulder,
      and Hand (DASH) and Kerlan-Jobe Orthopaedic Clinic (KJOC) scores from 106
      healthy, uninjured throwing athletes. Known-groups validity was estimated using
      FAST scores from 557 throwing athletes who were injured (n = 142) and uninjured
      (n = 415). Reliability and validity were assessed using intraclass correlation
      coefficients (ICCs), and measurement error was assessed using standard error of
      measurement (SEM) and minimum detectable change (MDC). Receiver operating
      characteristic curves and sensitivity/specificity values were estimated for known
      groups validity. Data from a separate group (n = 18) of postsurgical and
      nonoperative/conservative rehabilitation patients were analyzed to report
      responsiveness of the FAST. RESULTS: The FAST total, subscales, and pitcher
      module scores demonstrated excellent test-retest reliability (ICC, 0.91-0.98).
      The SEM95 and MDC95 for the FAST total score were 3.8 and 10.5 points,
      respectively. The SEM95 and MDC95 for the pitcher module score were 5.7 and 15.7
      points, respectively. The FAST scores showed acceptable correlation with DASH
      (ICC, 0.49-0.82) and KJOC (ICC, 0.62-0.81) scores. The FAST total score
      classified 85.1% of players into the correct injury group. For predicting UE
      injury status, a FAST total cutoff score of 10.0 out of 100.0 was 91% sensitive
      and 75% specific, and a pitcher module score of 10.0 out of 100.0 was 87%
      sensitive and 78% specific. The FAST total score demonstrated responsiveness on
      several indices between intake and discharge time points. CONCLUSION: The FAST is
      a reliable, valid, and responsive UE region-specific and population-specific PRO
      scale for measuring patient-reported health care outcomes in throwing athletes
      with injury.

PMID- 28451615
TI  - Outcomes After Posterior Cruciate Ligament (PCL) Reconstruction in Patients With
      Isolated and Combined PCL Tears.
AB  - BACKGROUND: Posterior cruciate ligament (PCL) reconstructions are rarely
      performed compared with that for the anterior cruciate ligament (ACL). PURPOSE:
      To evaluate the clinical and functional outcome after isolated or multiligament
      PCL reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS:
      Patients who underwent PCL reconstruction between 2002 and 2010 were included.
      Standardized follow-up was performed between 2012 and 2013 and consisted of
      subjective scores (Tegner activity score, Knee injury and Osteoarthritis Outcome
      Score [KOOS], and subjective International Knee Documentation Committee [IKDC]
      score) and objective measures, including knee laxity (KT-1000), extension
      strength, and overall IKDC score. RESULTS: One hundred ninety-six patients were
      identified, of which 172 were available for postoperative follow-up: 39.3% with
      isolated PCL and 60.7% with multiligament injury. One hundred ten patients were
      available to complete both clinical follow-up and subjective questionnaires; 62
      patients returned the subjective questionnaires. Mean follow-up was 5.9 years
      (range, 3.1-9.7 years). KOOS scores at follow-up in the isolated PCL group by
      subscale were 74 (symptoms), 76 (pain), 80 (activities of daily living), 55
      (sport), and 55 (quality of life). Scores for patients in the multiligament group
      were 73 (symptoms), 79 (pain), 82 (activities of daily living), 53 (sport), and
      56 (quality of life). Tegner scores were 4.5 and 4.4, respectively, and
      subjective IKDC scores were 63.8 and 65.0. The mean side-to-side difference in
      knee laxity was 2.7 mm in the isolated PCL group compared with 2.8 mm in the
      multiligament group. At 1-year follow-up there were significant differences in
      KOOS outcome scores between the isolated PCL subgroup and the multiligament
      subgroup, but no differences at final follow-up. Twelve patients (5%) had PCL
      revision surgery within the follow-up period. CONCLUSION: Despite the type of
      injury, there were only minor differences in knee laxity and subjective outcome
      scores between the isolated PCL group and the multiligament group. The overall
      revision rate in this study was 5.2%.

PMID- 28451616
TI  - Relationship Between the Lateral Center-Edge Angle and 3-Dimensional Acetabular
      Coverage.
AB  - BACKGROUND: The lateral center-edge angle (LCEA) is an important measurement in
      understanding acetabular morphology and has had multiple interpretations.
      Misunderstanding of the LCEA and its relationship with acetabular 3-dimensional
      (3D) morphology may result in misdiagnosis and poor outcomes. PURPOSE: To
      determine the discrepancy between bone-edge and sourcil-edge LCEA measurements on
      anteroposterior (AP) radiographs and to determine the 3D anatomic location of the
      sourcil-edge and bone-edge LCEA measurements. STUDY DESIGN: Cohort study
      (diagnosis); Level of evidence, 2. METHODS: The LCEA was measured on radiographs
      to both the sourcil-edge and bone-edge on AP images of 60 symptomatic hips. On
      computed tomography (CT), coronal slices producing an LCEA matching the magnitude
      of each AP LCEA were identified. These coronal slices were mapped to a sagittal
      image of the acetabulum, which was divided into a standard clockface (3 =
      anterior, 12 = superior). We identified clockface locations corresponding to the
      AP sourcil-edge and bone-edge LCEA measurements. Paired t tests identified
      differences in magnitude and location of the bone and sourcil LCEAs. Limits of
      agreement were calculated for the differences between measures. Intraclass
      correlation coefficients (ICCs) assessed inter- and intraobserver repeatability.
      RESULTS: On the AP radiographs, the bone-edge LCEA was a mean 4.7 degrees  (95%
      CI, -4.0 degrees  to 13.3 degrees ) greater than the sourcil-edge LCEA (P <
      .001). On CT, the sagittal clockface location of the sourcil-edge LCEA was more
      anterior compared with the sagittal clockface location of the maximum bone-edge
      LCEA (1:03 +/- 0:42 vs 12:06 +/- 0:30, respectively; P < .001). In hips with a
      difference >5 degrees  between sourcil-edge and bone-edge measurements, the
      coronal CT slice corresponding to the sourcil-edge LCEA was significantly more
      anterior (1:26 +/- 0:35) than the CT slice corresponding to the bone-edge LCEA
      (11:46 +/- 0:29; P < .001). This significant difference was similar in location
      but less pronounced in hips with a difference <=5 degrees : the sourcil-edge LCEA
      occurred at 12:50 +/- 0:40, while the bone-edge LCEA occurred at 12:00 +/- 0:11
      (P < .001). Interobserver repeatability was excellent for all LCEA and clockface
      location measurements (all ICCs >0.82). CONCLUSION: The sourcil-edge LCEA
      represents anterosuperior acetabular coverage while the bone-edge LCEA represents
      superior/lateral coverage. This information can be used in preoperative
      evaluation of and perioperative planning for hip preservation procedures.

PMID- 28451617
TI  - Return to Sport for Skeletally Immature Athletes After ACL Reconstruction:
      Preventing a Second Injury Using a Quality of Movement Assessment and
      Quantitative Measures to Address Modifiable Risk Factors.
AB  - BACKGROUND: Reinjury rates after anterior cruciate ligament reconstruction (ACLR)
      are highest among young athletes, who consequently suffer from low rates of
      return to play. Historically, quantitative measures have been used to determine
      readiness to return to sport; however, they do not assess modifiable risk factors
      related to the quality of movement. PURPOSE: To determine the effectiveness of a
      criteria-based rehabilitation progression and return-to-sport criteria on
      efficient return to activity and prevention of second injury in young athletes
      post-ACLR. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between
      December 2010 and 2013, 42 skeletally immature athletes (mean chronologic age, 12
      years; range, 10-15 years) who underwent ACLR using ipsilateral hamstring tendon
      autograft were prospectively evaluated. All athletes progressed through a
      criteria-based rehabilitation progression; were assessed at specific time frames
      for strength, biomechanical, and neuromuscular risk factors predictive of injury;
      and were provided targeted interventions. The final return to sport phase
      consisted of quantitative testing as well as a quality of movement assessment of
      several functional movements with progressive difficulty and sports-specific
      loading. Clearance for unrestricted activity was determined by achieving
      satisfactory results on both qualitative and quantitative assessments with
      consideration for the demands of each sport. RESULTS: The mean time for return to
      unrestricted competitive activity was 12 months. All but 3 (7%) athletes returned
      to their primary sport. Thirty-five athletes (83%) returned to unrestricted
      activity. Of the 6 (14%) who sustained a second injury, 3 (50%) were injured in
      sports they were not cleared for. All ACL reinjuries occurred in a cutting sport.
      Half of reinjuries occurred within 1 year of surgery, while the remaining
      occurred between 1 and 2 years. Eighty-three percent of reinjuries involved
      highly competitive cutting athletes. CONCLUSION: In our cohort, the combination
      of qualitative and quantitative data served as a good indicator for reducing risk
      and determining readiness to return to sport.

PMID- 28451618
TI  - Factors Associated With Improved Function and Maintenance of Sports Activities at
      5 to 10 Years After Autologous Hamstring ACL Reconstruction in Young Men.
AB  - BACKGROUND: There are limited data regarding associated factors of return to
      sports activities at more than 5 years after anterior cruciate ligament (ACL)
      reconstruction. PURPOSE: To test interrelationships between patient
      characteristics, concomitant articular lesions, graft laxity, and maintenance of
      sports activities at 5 to 10 years after ACL reconstruction. It was hypothesized
      that at 5 to 10 years after the operation in young adult men, maintenance of
      greater activity level and better knee function would be associated with greater
      preinjury activity level, younger age at reconstruction, absence of concomitant
      articular lesions, and minimal graft laxity at follow-up. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: One hundred six men with autologous
      hamstring ACL reconstruction between the ages of 18 and 35 years were reviewed at
      5 to 10 years after surgery. Excluded patients had contralateral ACL tear,
      revision reconstruction, or another injury impairing function. Fifty-five
      patients were eligible and available for follow-up. Independent variables
      included preinjury Tegner score, time interval from injury to surgery, smoking
      status, age, articular lesions, KT side-to-side difference, and pivot-shift
      grade. Main outcome measures were Tegner activity level, International Knee
      Documentation Committee (IKDC) subjective score, and Knee injury and
      Osteoarthritis Outcome Scale (KOOS) score at 5 to 10 years after surgery.
      RESULTS: Greater Tegner activity level at follow-up was associated in a
      regression model with greater preinjury Tegner activity level (correlation
      coefficient, 0.423; P = .01), lower KT difference (correlation coefficient, 
      0.278; P = .04), and negative pivot shift (correlation coefficient, -0.277; P =
      .05). Younger age at operation predicted return to greater Tegner activity level
      in a univariate analysis (correlation coefficient, -0.266; P = .05) but not in a
      regression model (not significant). Chondral lesions at surgery predicted lower
      IKDC subjective scores (71.4 +/- 14.3 vs 84.1 +/- 11.5; P < .01) and KOOS scores
      but did not affect maintenance of sports activities. CONCLUSION: At 5 to 10 years
      after autologous hamstring ACL reconstruction in young men, predictors of greater
      sports activity level are primarily high preinjury activity level and
      reestablishment of knee laxity. Younger age at operation and moderate chondral
      lesions have lower impact in this respect.

PMID- 28451619
TI  - Tape Versus Suture in Arthroscopic Rotator Cuff Repair: Biomechanical Analysis
      and Assessment of Failure Rates at 6 Months.
AB  - BACKGROUND: Rotator cuff retears after surgical repair are associated with poorer
      subjective and objectives clinical outcomes than intact repairs. PURPOSE: The
      aims of this study were to (1) examine the biomechanical differences between
      rotator cuff repair using No. 2 suture and tape in an ovine model and (2) compare
      early clinical outcomes between patients who had rotator cuff repair with tape
      and patients who had repair with No. 2 suture. STUDY DESIGN: Controlled
      laboratory study and cohort study; Level of evidence, 3. METHODS: Biomechanical
      testing of footprint contact pressure and load to failure were conducted with 16
      ovine shoulders using a tension band repair technique with 2 different types of
      sutures (No. 2 suture [FiberWire; Arthrex] and tape [FiberTape; Arthrex]) with
      the same knotless anchor system. A retrospective study of 150 consecutive
      patients (tape, n = 50; suture, n = 100) who underwent arthroscopic rotator cuff
      repair by a single surgeon with tear size larger than 1.5 * 1 cm was conducted.
      Ultrasound was used to evaluate the repair integrity at 6 months postsurgery.
      RESULTS: Rotator cuff repair using tape had greater footprint contact pressure
      (mean +/- standard error of the mean, 0.33 +/- 0.03 vs 0.11 +/- 0.3 MPa; P <
      .0001) compared with repair using No. 2 sutures at 0 degrees  abduction with a 30
      N load applied across the repaired tendon. The ultimate failure load of the tape
      repair was greater than that for suture repair (217 +/- 28 vs 144 +/- 14 N; P <
      .05). The retear rate was similar between the tape (16%; 8/50) and suture groups
      (17%; 17/100). CONCLUSION: Rotator cuff repair with the wider tape compared with
      No. 2 suture did not affect the retear rate at 6 months postsurgery, despite
      having superior biomechanical properties.

PMID- 28451620
TI  - Generalized Joint Hypermobility Is Predictive of Hip Capsular Thickness.
AB  - BACKGROUND: The pathomechanics of hip microinstability are not clearly defined
      but are thought to involve anatomical abnormalities, repetitive forces across the
      hip, and ligamentous laxity. PURPOSE/HYPOTHESIS: The purpose of this study was to
      explore the relationship between generalized joint hypermobility (GJH) and hip
      capsular thickness. The hypothesis was that GJH would be predictive of a thin hip
      capsule. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A
      prospective study was performed on 100 consecutive patients undergoing primary
      hip arthroscopy for the treatment of hip pain. A Beighton test score (BTS) was
      obtained prior to each procedure. The maximum score was 9, and a score of >=4 was
      defined as hypermobile. Capsular thickness at the level of the anterior portal,
      corresponding to the location of the iliofemoral ligament, was measured
      arthroscopically using a calibrated probe. The presence of ligamentum teres (LT)
      pathology was also recorded. RESULTS: Fifty-five women and 45 men were included
      in the study. The mean age was 32 years (range, 18-45 years). The median hip
      capsule thickness was statistically greater in men than women (12.5 and 7.5 mm,
      respectively). The median BTS for men was 1 compared with 4 for women (P < .001).
      A statistically significant association was found between BTS and capsular
      thickness; a BTS of <4 is strongly predictive of having a capsular thickness of
      >=10 mm, while a BTS >=4 correlates with a capsular thickness of <10 mm. There
      was a statistically greater incidence of LT tears in patients with a capsular
      thickness of <=7.5 mm and a BTS of >=4 (P < .001). CONCLUSION: Measurement of the
      GJH is highly predictive of hip capsular thickness. A BTS of <4 correlates
      significantly with a capsular thickness of >=10 mm, while a BTS >=4 correlates
      significantly with a thickness of <10 mm.

PMID- 28451621
TI  - Is There an Association Between the "Critical Shoulder Angle" and Clinical
      Outcome After Rotator Cuff Repair?
AB  - BACKGROUND: Variations in scapular morphology have been associated with the
      development of atraumatic rotator cuff tears (RCTs). The critical shoulder angle
      (CSA) accounts for both glenoid inclination and lateral extension of the
      acromion. The impact of the CSA on outcomes after rotator cuff repair (RCR) has
      not been investigated previously. HYPOTHESIS: Our hypothesis was that individuals
      with smaller CSAs will have better patient-reported outcome scores over time
      compared with those with larger CSAs. Theoretically, a smaller CSA minimizes the
      biomechanical forces favoring superior translation of the humeral head, which may
      be advantageous after RCR. This is the first study to examine the relationship
      between the CSA and clinical outcomes after RCR. STUDY DESIGN: Cohort study;
      Level of evidence, 2. METHODS: Fifty-three patients (mean age, 61 years) with
      atraumatic full-thickness RCTs who underwent arthroscopic RCR were prospectively
      evaluated. Demographic data as well as the Western Ontario Rotator Cuff Index
      (WORC) score, American Shoulder and Elbow Surgeons (ASES) score, and a visual
      analog scale (VAS) for pain were prospectively collected at various time points
      up to 24 months postoperatively. Statistical analysis included longitudinal
      multilevel regression modeling to investigate the association between the CSA and
      the WORC, ASES, and VAS scores. RESULTS: The overall clinical outcome, as
      measured by the WORC, ASES, and VAS, improved significantly (P < .0001).
      Controlling for demographic and clinical characteristics, a multilevel regression
      analysis demonstrated that the CSA was not a significant independent predictor
      for change in WORC (P = .581), ASES (P = .458), or VAS (P = .859) scores at 24
      months after arthroscopic RCR. Interobserver and intraobserver reliability for
      CSA measurements resulted in interclass correlation coefficients of 0.986 and
      0.982, respectively (P < .001), indicating excellent agreement. CONCLUSION: The
      CSA did not appear to be a significant predictor of patient-reported outcomes
      after arthroscopic repair of atraumatic full-thickness RCTs.

PMID- 28451622
TI  - The Effects of Elbow Bracing on Medial Elbow Joint Space Gapping Associated With
      Repetitive Throwing in High School Baseball Players.
AB  - BACKGROUND: Throwing athletes risk medial elbow injury from extreme valgus stress
      generated across the medial elbow during throwing. Braces have been developed to
      protect the elbow joint; however, no previous study has investigated the effects
      of elbow bracing on medial elbow joint space gapping associated with repetitive
      throwing. HYPOTHESIS/PURPOSE: The purpose of this study was to investigate the
      effects of elbow bracing on medial elbow joint space gapping during repetitive
      throwing. Our hypothesis was that an elbow brace may reduce mechanical stress on
      the elbow by reducing medial elbow joint space gapping. STUDY DESIGN: Controlled
      laboratory study. METHODS: Twenty-five high school baseball players participated
      in this study. Each subject pitched 100 times under 2 conditions: control
      (without elbow brace) and elbow brace. The ulnohumeral joint space was measured
      ultrasonically before pitching and after every block of 20 pitches. Measurement
      of the ulnohumeral joint space was carried out using ultrasound with the forearm
      hanging by the side. Two-way repeated-measures analysis of variance and post hoc
      tests were used to compare ulnohumeral joint space with repeated pitching and
      between the elbow brace and control conditions. RESULTS: In the control
      condition, ulnohumeral joint space after 60 pitches was significantly greater
      than that before pitching (P < .01). In contrast, in the elbow brace condition,
      ulnohumeral joint space was not significantly different after repeated pitching.
      When comparing these 2 conditions, ulnohumeral joint space in the control
      condition was significantly greater than that in the elbow brace condition after
      60 pitches (P < .01). CONCLUSION: An elbow brace has the effect of preventing
      medial elbow joint space gapping with repeated throwing when determined
      ultrasonically by measuring the ulnohumeral joint space under gravity load.
      CLINICAL RELEVANCE: An elbow brace worn during baseball pitching practice may
      help reduce mechanical stress on the elbow by reducing medial elbow joint space
      gapping.

PMID- 28451623
TI  - Accelerated Return to Sport After Osteochondral Autograft Plug Transfer.
AB  - BACKGROUND: Previous studies have reported varying return-to-sport protocols
      after knee cartilage restoration procedures. PURPOSE: To (1) evaluate the time
      for return to sport in athletes with an isolated chondral injury who underwent an
      accelerated return-to-sport protocol after osteochondral autograft plug transfer
      (OAT) and (2) evaluate clinical outcomes to assess for any consequences from the
      accelerated return to sport. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: An institutional cohort of 152 OAT procedures was reviewed, of which 20
      competitive athletes met inclusion and exclusion criteria. All patients underwent
      a physician-directed accelerated rehabilitation program after their procedure.
      Return to sport was determined for all athletes. Clinical outcomes were assessed
      using International Knee Documentation Committee (IKDC) and Tegner scores as well
      as assessment of level of participation on return to sport. RESULTS: Return-to
      sport data were available for all 20 athletes; 13 of 20 athletes (65%) were
      available for clinical evaluation at a mean 4.4-year follow-up. The mean time for
      return to sport for all 20 athletes was 82.9 +/- 25 days (range, 38-134 days).
      All athletes were able to return to sport at their previous level and reported
      that they were satisfied or very satisfied with their surgical outcome and
      ability to return to sport. The mean postoperative IKDC score was 84.5 +/- 9.5.
      The mean Tegner score prior to injury was 8.9 +/- 1.7; it was 7.7 +/- 1.9 at
      final follow-up. CONCLUSION: Competitive athletes with traumatic chondral defects
      treated with OAT managed using this protocol had reduced time to preinjury
      activity levels compared with what is currently reported, with excellent clinical
      outcomes and no serious long-term sequelae.

PMID- 28451625
TI  - Optical resonance imaging: An optical analog to MRI with sub-diffraction-limited
      capabilities.
AB  - We propose here optical resonance imaging (ORI), a direct optical analog to
      magnetic resonance imaging (MRI). The proposed pulse sequence for ORI maps space
      to time and recovers an image from a heterodyne-detected third-order nonlinear
      photon echo measurement. As opposed to traditional photon echo measurements, the
      third pulse in the ORI pulse sequence has significant pulse-front tilt that acts
      as a temporal gradient. This gradient couples space to time by stimulating the
      emission of a photon echo signal from different lateral spatial locations of a
      sample at different times, providing a widefield ultrafast microscopy. We
      circumvent the diffraction limit of the optics by mapping the lateral spatial
      coordinate of the sample with the emission time of the signal, which can be
      measured to high precision using interferometric heterodyne detection. This
      technique is thus an optical analog of MRI, where magnetic-field gradients are
      used to localize the spin-echo emission to a point below the diffraction limit of
      the radio-frequency wave used. We calculate the expected ORI signal using 15 fs
      pulses and 87 degrees  of pulse-front tilt, collected using f/2 optics and find a
      two-point resolution 275 nm using 800 nm light that satisfies the Rayleigh
      criterion. We also derive a general equation for resolution in optical resonance
      imaging that indicates that there is a possibility of superresolution imaging
      using this technique. The photon echo sequence also enables spectroscopic
      determination of the input and output energy. The technique thus correlates the
      input energy with the final position and energy of the exciton.

PMID- 28451624
TI  - Tics in the Pediatric Population: Pragmatic Management.
AB  - BACKGROUND: Primary tic disorders, notably Tourette syndrome, are very common
      movement disorders in childhood. However, the management of such patients still
      poses great therapeutic challenges to medical professionals. METHODS: Based on a
      synthesis of the available guidelines published in Europe, Canada, and the United
      States, coupled with more recent therapeutic developments, the authors provide a
      pragmatic guide to aid clinicians in deciding when and how to treat patients who
      have primary tic disorders. RESULTS: After a systematic assessment of tics and
      common neuropsychiatric comorbidities (primarily attention-deficit hyperactivity
      disorder [ADHD] and obsessive-compulsive disorder [OCD]), the first step in
      treatment is a comprehensive psychoeducation of patients and families that
      addresses the protean phenomenology of tics and associated behaviors, coping
      mechanisms, prognosis, and treatment options. When more active intervention
      beyond watchful monitoring is indicated, hierarchical evaluation of treatment
      targets (i.e., tics vs. comorbid behavioral symptoms) is crucial. Behavioral
      treatments for tics are restricted to older children and are not readily
      available to all centers, mainly due to the paucity of well-trained therapists.
      Pharmacological treatments, such as antipsychotics for tics, stimulants and
      atomoxetine for ADHD, and alpha2A-agonists for children with tics plus ADHD,
      represent widely available and effective treatment options, but safety monitoring
      must be provided. Combined polypharmacological and behavioral/pharmacological
      approaches, as well as neuromodulation strategies, remain under-investigated in
      this population of patients. CONCLUSIONS: The treatment of children with tics and
      Tourette syndrome is multifaceted. Multidisciplinary teams with expertise in
      neurology, psychiatry, psychology, and pediatrics may be helpful to address the
      complex needs of these children.

PMID- 28451626
TI  - Contribution of blood vessels to retinal nerve fiber layer thickness in NMOSD.

PMID- 28451627
TI  - Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum
      disorder.
AB  - OBJECTIVE: To describe leptomeningeal blood-barrier impairment reflected by MRI
      gadolinium-enhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4
      IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: A
      retrospective case series of 11 AQP4-IgG-positive NMOSD patients with
      leptomeningeal enhancement (LME) were collected from 5 centers. External
      neuroradiologists, blinded to the clinical details, evaluated MRIs. RESULTS: LME
      was demonstrated on postcontrast T1-weighted and fluid-attenuated inversion
      recovery images as a sign of leptomeningeal blood-barrier disruption and
      transient leakage of contrast agent into the subarachnoid space in 11 patients, 6
      in the brain and 6 in the spinal cord. The patterns of LME were linear or
      extensive and were accompanied by periependymal enhancement in 5 cases and
      intraparenchymal enhancement in all cases. The location of LME in the spinal cord
      was adjacent to intraparenchymal contrast enhancement with involvement of a
      median number of 12 (range 5-17) vertebral segments. At the time of LME on MRI,
      all patients had a clinical attack such as encephalopathy (36%) and/or myelopathy
      (70%) with median interval between symptom onset and LME of 12 days (range 2-30).
      LME occurred in association with an initial area postrema attack (44%), signs of
      systemic infection (33%), or AQP4-IgG in CSF (22%) followed by clinical
      progression. LME was found at initial clinical presentation in 5 cases and at
      clinical relapses leading to a diagnosis of NMOSD in 6 cases. CONCLUSION: This
      study suggests that altered leptomeningeal blood barrier may be accompanied by
      intraparenchymal blood-brain barrier breakdown in patients with AQP4-IgG-positive
      NMOSD during relapses.

PMID- 28451628
TI  - Linking Spiritual and Religious Coping With the Quality of Life of Community
      Dwelling Older Adults and Nursing Home Residents.
AB  - Objective: This study examined the effect of Positive and Negative Spiritual and
      Religious Coping (SRC) upon older Brazilian's quality of life (QOL). Method: A
      secondary analysis of data collected from 77 nursing home residents (NHRs; M age
      = 76.56) and 326 community-dwelling residents (CDRs; M age = 67.22 years) was
      conducted. Participants had completed the Brief SRC, and the World Health
      Organization Quality of Life-BREF (WHOQOL-BREF) and World Health Organization
      Quality of Life-OLD (WHOQOL-OLD). A General Linear Model regression analysis was
      undertaken to assess the effects of SRC upon 10 aspects of participants' QOL.
      Results: Positive (F = 6.714, df = 10, p < .001) as opposed to Negative (F =
      1.194, df = 10, p = .294) SRC was significantly associated with QOL. Positive SRC
      was more strongly associated with NHR's physical, psychological, and
      environmental QOL, and their perceived sensory abilities, autonomy, and
      opportunities for intimacy. Conclusion: Positive SRC behaviors per se were
      significantly associated with QOL ratings across both study samples. The effect
      size of Positive SRC was much larger among NHRs across six aspects of QOL. Place
      of residence (POR) in relation to SRC and QOL in older age warrants further
      study.

PMID- 28451629
TI  - Neuroinflammation-a co-occurring phenomenon linking chronic pain and opioid
      dependence.
AB  - Chronic pain is a disease that encompasses both sensory and emotional elements.
      Opioids are highly effective analgesics because they target both of these
      elements, by inhibiting pain pathways and alleviating negative affect (including
      depression) by engaging reward or hedonic pathways. Unfortunately, chronic opioid
      use is limited by the development of unwanted side effects, such as tolerance,
      hyperalgesia, and abuse liability. Thus, the challenge of providing effective
      pain treatment while minimizing these unwanted side effects is an ongoing issue
      with significant clinical and societal impact. In this review, we posit that
      neuroinflammation within the central nervous system is a shared phenomenon
      between chronic pain and opioids that contributes to pain sensitization and
      negative affect. The implications for pain progression, addiction liability, and
      alternative treatment strategies are discussed.

PMID- 28451630
TI  - Hearing Scenes: A Neuromagnetic Signature of Auditory Source and Reverberant
      Space Separation.
AB  - Perceiving the geometry of surrounding space is a multisensory process, crucial
      to contextualizing object perception and guiding navigation behavior. Humans can
      make judgments about surrounding spaces from reverberation cues, caused by sounds
      reflecting off multiple interior surfaces. However, it remains unclear how the
      brain represents reverberant spaces separately from sound sources. Here, we
      report separable neural signatures of auditory space and source perception during
      magnetoencephalography (MEG) recording as subjects listened to brief sounds
      convolved with monaural room impulse responses (RIRs). The decoding signature of
      sound sources began at 57 ms after stimulus onset and peaked at 130 ms, while
      space decoding started at 138 ms and peaked at 386 ms. Importantly, these
      neuromagnetic responses were readily dissociable in form and time: while sound
      source decoding exhibited an early and transient response, the neural signature
      of space was sustained and independent of the original source that produced it.
      The reverberant space response was robust to variations in sound source, and vice
      versa, indicating a generalized response not tied to specific source-space
      combinations. These results provide the first neuromagnetic evidence for robust,
      dissociable auditory source and reverberant space representations in the human
      brain and reveal the temporal dynamics of how auditory scene analysis extracts
      percepts from complex naturalistic auditory signals.

PMID- 28451631
TI  - GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and
      Behavioral Deficits in the Fmr1 Knockout Mouse Model of Fragile X Syndrome.
AB  - Fragile X syndrome is a genetic condition resulting from FMR1 gene mutation that
      leads to intellectual disability, autism-like symptoms, and sensory
      hypersensitivity. Arbaclofen, a GABA-B agonist, has shown efficacy in some
      individuals with FXS but has become unavailable after unsuccessful clinical
      trials, prompting interest in publicly available, racemic baclofen. The present
      study investigated whether racemic baclofen can remediate abnormalities of neural
      circuit function, sensory processing, and behavior in Fmr1 knockout mice, a
      rodent model of fragile X syndrome. Fmr1 knockout mice showed increased baseline
      and auditory-evoked high-frequency gamma (30-80 Hz) power relative to C57BL/6
      controls, as measured by electroencephalography. These deficits were accompanied
      by decreased T maze spontaneous alternation, decreased social interactions, and
      increased open field center time, suggestive of diminished working memory,
      sociability, and anxiety-like behavior, respectively. Abnormal auditory-evoked
      gamma oscillations, working memory, and anxiety-related behavior were normalized
      by treatment with baclofen, but impaired sociability was not. Improvements in
      working memory were evident predominantly in mice whose auditory-evoked gamma
      oscillations were dampened by baclofen. These findings suggest that racemic
      baclofen may be useful for targeting sensory and cognitive disturbances in
      fragile X syndrome.

PMID- 28451632
TI  - Skill Learning Modulates RNA Pol II Poising at Immediate Early Genes in the Adult
      Striatum.
AB  - A multilayered complexity of epigenetic and transcriptional regulatory mechanisms
      underlies neuronal activity-dependent gene transcription. The regulation of RNA
      Pol II progression along the transcription cycle, from promoter-proximal poising
      (with RNA Pol II paused at promoter-proximal regions, characterized by a Ser5P+
      rich and Ser2P+-poor RPB1 CTD) to active elongation, has emerged as a major step
      in transcriptional regulation across several organisms, tissues, and
      developmental stages, including the nervous system. However, it is not known
      whether this mechanism is modulated by experience. We investigated the impact of
      learning a motor skill on RNA Pol II phosphorylation dynamics in the adult mouse
      striatum. We uncovered that learning modulates the in vivo striatal
      phosphorylation dynamics of the CTD of the RNA Pol II RPB1 subunit, leading to an
      increased poising index in trained mice. We found that this modulation occurs at
      immediate early genes (IEGs), with increased poising of RNA Pol II at both Arc
      and Fos genes but not at constitutively expressed genes. Furthermore, we
      confirmed that this was learning dependent, and not just regulated by context or
      motor activity. These experiments demonstrate a novel phenomenon of learning
      induced transcriptional modulation in adult brain, which may have implications
      for our understanding of learning, memory allocation, and consolidation.

PMID- 28451633
TI  - Individual Differences in Human Path Integration Abilities Correlate with Gray
      Matter Volume in Retrosplenial Cortex, Hippocampus, and Medial Prefrontal Cortex.
AB  - Humans differ in their individual navigational abilities. These individual
      differences may exist in part because successful navigation relies on several
      disparate abilities, which rely on different brain structures. One such
      navigational capability is path integration, the updating of position and
      orientation, in which navigators track distances, directions, and locations in
      space during movement. Although structural differences related to landmark-based
      navigation have been examined, gray matter volume related to path integration
      ability has not yet been tested. Here, we examined individual differences in two
      path integration paradigms: (1) a location tracking task and (2) a task tracking
      translational and rotational self-motion. Using voxel-based morphometry, we
      related differences in performance in these path integration tasks to variation
      in brain morphology in 26 healthy young adults. Performance in the location
      tracking task positively correlated with individual differences in gray matter
      volume in three areas critical for path integration: the hippocampus, the
      retrosplenial cortex, and the medial prefrontal cortex. These regions are
      consistent with the path integration system known from computational and animal
      models and provide novel evidence that morphological variability in retrosplenial
      and medial prefrontal cortices underlies individual differences in human path
      integration ability. The results for tracking rotational self-motion-but not
      translation or location-demonstrated that cerebellum gray matter volume
      correlated with individual performance. Our findings also suggest that these
      three aspects of path integration are largely independent. Together, the results
      of this study provide a link between individual abilities and the functional
      correlates, computational models, and animal models of path integration.

PMID- 28451634
TI  - Position Information Encoded by Population Activity in Hierarchical Visual Areas.
AB  - Neurons in high-level visual areas respond to more complex visual features with
      broader receptive fields (RFs) compared to those in low-level visual areas. Thus,
      high-level visual areas are generally considered to carry less information
      regarding the position of seen objects in the visual field. However, larger RFs
      may not imply loss of position information at the population level. Here, we
      evaluated how accurately the position of a seen object could be predicted
      (decoded) from activity patterns in each of six representative visual areas with
      different RF sizes [V1-V4, lateral occipital complex (LOC), and fusiform face
      area (FFA)]. We collected functional magnetic resonance imaging (fMRI) responses
      while human subjects viewed a ball randomly moving in a two-dimensional field. To
      estimate population RF sizes of individual fMRI voxels, RF models were fitted for
      individual voxels in each brain area. The voxels in higher visual areas showed
      larger estimated RFs than those in lower visual areas. Then, the ball's position
      in a separate session was predicted by maximum likelihood estimation using the RF
      models of individual voxels. We also tested a model-free multivoxel regression
      (support vector regression, SVR) to predict the position. We found that
      regardless of the difference in RF size, all visual areas showed similar
      prediction accuracies, especially on the horizontal dimension. Higher areas
      showed slightly lower accuracies on the vertical dimension, which appears to be
      attributed to the narrower spatial distributions of the RF centers. The results
      suggest that much position information is preserved in population activity
      through the hierarchical visual pathway regardless of RF sizes and is potentially
      available in later processing for recognition and behavior.

PMID- 28451635
TI  - Efficient Remyelination Requires DNA Methylation.
AB  - Oligodendrocyte progenitor cells (OPCs) are the principal source of new myelin in
      the central nervous system. A better understanding of how they mature into myelin
      forming cells is of high relevance for remyelination. It has recently been
      demonstrated that during developmental myelination, the DNA methyltransferase 1
      (DNMT1), but not DNMT3A, is critical for regulating proliferation and
      differentiation of OPCs into myelinating oligodendrocytes (OLs). However, it
      remains to be determined whether DNA methylation is also critical for the
      differentiation of adult OPCs during remyelination. After lysolecithin-induced
      demyelination in the ventrolateral spinal cord white matter of adult mice of
      either sex, we detected increased levels of DNA methylation and higher expression
      levels of the DNA methyltransferase DNMT3A and lower levels of DNMT1 in
      differentiating adult OLs. To functionally assess the role of DNMT1 and DNMT3 in
      adult OPCs, we used mice with inducible and lineage-specific ablation of Dnmt3a
      and/or Dnmt1 (i.e., Plp-creER(t);Dnmt3a-flox, Plp-creER(t);Dnmt1-flox, Plp
      creER(t);Dnmt1-flox;Dnmt3a-flox). Upon lysolecithin injection in the spinal cord
      of these transgenic mice, we detected defective OPC differentiation and
      inefficient remyelination in the Dnmt3a null and Dnmt1/Dnmt3a null mice, but not
      in the Dnmt1 null mice. Taken together with previous results in the developing
      spinal cord, these data suggest an age-dependent role of distinct DNA
      methyltransferases in the oligodendrocyte lineage, with a dominant role for DNMT1
      in neonatal OPCs and for DNMT3A in adult OPCs.

PMID- 28451636
TI  - The Isl1-Lhx3 Complex Promotes Motor Neuron Specification by Activating
      Transcriptional Pathways that Enhance Its Own Expression and Formation.
AB  - Motor neuron (MN) progenitor cells rapidly induce high expression of the
      transcription factors Islet-1 (Isl1), LIM-homeobox 3 (Lhx3), and the
      transcriptional regulator LMO4, as they differentiate. While these factors are
      critical for MN specification, the mechanisms regulating their precise temporal
      and spatial expression patterns are not well characterized. Isl1 and Lhx3 form
      the Isl1-Lhx3 complex, which induces the transcription of genes critical for MN
      specification and maturation. Here, we report that Isl1, Lhx3, and Lmo4 are
      direct target genes of the Isl1-Lhx3 complex. Our results show that specific
      genomic loci associated with these genes recruit the Isl1-Lhx3 complex to
      activate the transcription of Isl1, Lhx3, and Lmo4 in embryonic MNs of chick and
      mouse. These findings support a model in which the Isl1-Lhx3 complex amplifies
      its own expression through a potent autoregulatory feedback loop and
      simultaneously enhances the transcription of Lmo4. LMO4 blocks the formation of
      the V2 interneuron-specifying Lhx3 complex. In developing MNs, this action
      inhibits the expression of V2 interneuron genes and increases the pool of unbound
      Lhx3 available to incorporate into the Isl1-Lhx3 complex. Identifying the
      pathways that regulate the expression of these key factors provides important
      insights into the genetic strategies utilized to promote MN differentiation and
      maturation.

PMID- 28451637
TI  - Local and Long-Range Circuit Connections to Hilar Mossy Cells in the Dentate
      Gyrus.
AB  - Hilar mossy cells are the prominent glutamatergic cell type in the dentate hilus
      of the dentate gyrus (DG); they have been proposed to have critical roles in the
      DG network. To better understand how mossy cells contribute to DG function, we
      have applied new viral genetic and functional circuit mapping approaches to
      quantitatively map and compare local and long-range circuit connections of mossy
      cells and dentate granule cells in the mouse. The great majority of inputs to
      mossy cells consist of two parallel inputs from within the DG: an excitatory
      input pathway from dentate granule cells and an inhibitory input pathway from
      local DG inhibitory neurons. Mossy cells also receive a moderate degree of
      excitatory and inhibitory CA3 input from proximal CA3 subfields. Long range
      inputs to mossy cells are numerically sparse, and they are only identified
      readily from the medial septum and the septofimbrial nucleus. In comparison,
      dentate granule cells receive most of their inputs from the entorhinal cortex.
      The granule cells receive significant synaptic inputs from the hilus and the
      medial septum, and they also receive direct inputs from both distal and proximal
      CA3 subfields, which has been underdescribed in the existing literature. Our
      slice-based physiological mapping studies further supported the identified
      circuit connections of mossy cells and granule cells. Together, our data suggest
      that hilar mossy cells are major local circuit integrators and they exert
      modulation of the activity of dentate granule cells as well as the CA3 region
      through "back-projection" pathways.

PMID- 28451638
TI  - Stress Models of Depression: A Question of Bad Timing.

PMID- 28451639
TI  - Microglial TNFalpha Induces COX2 and PGI2 Synthase Expression in Spinal
      Endothelial Cells during Neuropathic Pain.
AB  - Prostaglandins (PGs) are typical lipid mediators that play a role in homeostasis
      and disease. They are synthesized from arachidonic acid by cyclooxygenase 1
      (COX1) and COX2. Although COX2 has been reported to be upregulated in the spinal
      cord after nerve injury, its expression and functional roles in neuropathic pain
      remain unclear. In this study, we investigated the expression of Cox2, PGI2
      synthase (Pgis), and prostaglandin I2 receptor (IP receptor) mRNA in the rat
      spinal cord after spared nerve injury (SNI). Levels of Cox2 and Pgis mRNA
      increased in endothelial cells from 24 to 48 h after nerve injury. IP receptor
      mRNA was constitutively expressed in dorsal horn neurons. A COX2 inhibitor and IP
      receptor antagonists attenuated pain behavior in the early phase of neuropathic
      pain. Furthermore, we examined the relationship between COX2 and tumor necrosis
      factor-alpha (TNFalpha) in the spinal cord of a rat SNI model. Levels of TNFalpha
      mRNA transiently increased in the spinal microglia 24 h after SNI. The TNF
      receptors Tnfr1 and Tnfr2 mRNA were colocalized with COX2. Intrathecal injection
      of TNFalpha induced Cox2 and Pgis mRNA expression in endothelial cells. These
      results revealed that microglia-derived TNFalpha induced COX2 and PGIS expression
      in spinal endothelial cells and that endothelial PGI2 played a critical role in
      neuropathic pain via neuronal IP receptor. These findings further suggest that
      the glia-endothelial cell interaction of the neurovascular unit via transient
      TNFalpha is involved in the generation of neuropathic pain.

PMID- 28451640
TI  - Cortical Activation Patterns Evoked by Temporally Asymmetric Sounds and Their
      Modulation by Learning.
AB  - When complex sounds are reversed in time, the original and reversed versions are
      perceived differently in spectral and temporal dimensions despite their identical
      duration and long-term spectrum-power profiles. Spatiotemporal activation
      patterns evoked by temporally asymmetric sound pairs demonstrate how the temporal
      envelope determines the readout of the spectrum. We examined the patterns of
      activation evoked by a temporally asymmetric sound pair in the primary auditory
      field (AI) of anesthetized guinea pigs and determined how discrimination training
      modified these patterns. Optical imaging using a voltage-sensitive dye revealed
      that a forward ramped-down natural sound (F) consistently evoked much stronger
      responses than its time-reversed, ramped-up counterpart (revF). The
      spatiotemporal maximum peak (maxP) of F-evoked activation was always greater than
      that of revF-evoked activation, and these maxPs were significantly separated
      within the AI. Although discrimination training did not affect the absolute
      magnitude of these maxPs, the revF-to-F ratio of the activation peaks calculated
      at the location where hemispheres were maximally activated (i.e., F-evoked maxP)
      was significantly smaller in the trained group. The F-evoked activation
      propagated across the AI along the temporal axis to the ventroanterior belt field
      (VA), with the local activation peak within the VA being significantly larger in
      the trained than in the naive group. These results suggest that the innate
      network is more responsive to natural sounds of ramped-down envelopes than their
      time-reversed, unnatural sounds. The VA belt field activation might play an
      important role in emotional learning of sounds through its connections with
      amygdala.

PMID- 28451643
TI  - SCA8 should not be tested in isolation for ataxia.

PMID- 28451641
TI  - An Aversive Response to Osmotic Upshift in Caenorhabditis elegans.
AB  - Environmental osmolarity presents a common type of sensory stimulus to animals.
      While behavioral responses to osmotic changes are important for maintaining a
      stable intracellular osmolarity, the underlying mechanisms are not fully
      understood. In the natural habitat of Caenorhabditis elegans, changes in
      environmental osmolarity are commonplace. It is known that the nematode acutely
      avoids shocks of extremely high osmolarity. Here, we show that C. elegans also
      generates gradually increased aversion of mild upshifts in environmental
      osmolarity. Different from an acute avoidance of osmotic shocks that depends on
      the function of a transient receptor potential vanilloid channel, the slow
      aversion to osmotic upshifts requires the cGMP-gated sensory channel subunit TAX
      2. TAX-2 acts in several sensory neurons that are exposed to body fluid to
      generate the aversive response through a motor network that underlies navigation.
      Osmotic upshifts activate the body cavity sensory neuron URX, which is known to
      induce aversion upon activation. Together, our results characterize the molecular
      and cellular mechanisms underlying a novel sensorimotor response to osmotic
      stimuli and reveal that C. elegans engages different behaviors and the underlying
      mechanisms to regulate responses to extracellular osmolarity.

PMID- 28451642
TI  - Impulsive Rats Exhibit Blunted Dopamine Release Dynamics during a Delay
      Discounting Task Independent of Cocaine History.
AB  - The inability to wait for a large, delayed reward when faced with a small,
      immediate one, known as delay discounting, has been implicated in a number of
      disorders including substance abuse. Individual differences in impulsivity on the
      delay discounting task are reflected in differences in neural function, including
      in the nucleus accumbens (NAc) core. We examined the role of a history of cocaine
      self-administration, as well as individual differences in impulsivity, on rapid
      dopamine (DA) release dynamics in the NAc core. Rats with a history of cocaine or
      water/saline self-administration were tested on delay discounting while being
      simultaneously assayed for rapid DA release using electrochemical methods. In
      controls, we found that cue DA release was modulated by reward delay and
      magnitude, consistent with prior reports. A history of cocaine had no effect on
      either delay discounting or DA release dynamics. Nonetheless, independent of drug
      history, individual differences in impulsivity were related to DA release in the
      NAc core. First, high impulsive animals exhibited dampened cue DA release during
      the delay discounting task. Second, reward delay and magnitude in high impulsive
      animals failed to robustly modulate changes in cue DA release. Importantly, these
      two DAergic mechanisms were uncorrelated with each other and, together, accounted
      for a high degree of variance in impulsive behavior. Collectively, these findings
      demonstrate two distinct mechanisms by which rapid DA signaling may influence
      impulsivity, and illustrate the importance of NAc core DA release dynamics in
      impulsive behavior.

PMID- 28451644
TI  - Robot-Assisted Laparoscopic Prostatectomy in a Prostate Cancer Patient Undergoing
      Continuous Ambulatory Peritoneal Dialysis.
AB  - Background: Robot-assisted laparoscopic prostatectomy (RALP) has become the gold
      standard treatment for organ-confined prostate cancer. However, no proper
      surgical approach or appropriate postsurgical management of RALP has been
      established for a patient undergoing peritoneal dialysis. Here, we present a case
      of a peritoneal dialysis patient who underwent RALP and reinstated peritoneal
      dialysis with no trouble associated with peritoneal dialysis. Case Presentation:
      The patient was a 61-year-old man with organ-confined prostate cancer. He had
      been on peritoneal dialysis for 2 years. The peritoneal dialysis catheter was
      routed subcutaneously from the left lateral region into the abdominal cavity at
      the paramedian region. RALP was performed by the transperitoneal anterior
      approach. The surgical maneuver was not influenced by the peritoneal dialysis
      catheter at all. At the end of surgery, the incised peritoneum was sutured and
      closed tightly. After surgery, peritoneal dialysis was temporarily interrupted
      for 2 weeks. Then it was safely reinitiated with no complications. Conclusion:
      Transperitoneal RALP with complete peritoneal repair can be a standard treatment
      option for a prostate cancer patient undergoing peritoneal dialysis.

PMID- 28451645
TI  - Frailty and quality of life in adult survivors of childhood cancer.
AB  - INTRODUCTION: Adult survivors of childhood cancer are at risk for frailty, a
      state of diminished physiologic reserve, typically seen in older adults,
      associated with morbidity and mortality. They are also at risk for poor quality
      of life. This review explores potential associations between frailty and quality
      of life and proposes potential interventions that may prevent or remediate frail
      health. AREAS COVERED AND LITERATURE SEARCH: A literature search using MEDLINE
      and EMBASE was undertaken using key words: childhood cancer survivors and each of
      the following: frailty, physical performance, emotional health, and quality of
      life. 796 abstracts were reviewed for relevance. Reference lists for retrieved
      articles were consulted for pertinent manuscripts (N=40). Recent literature (from
      January 2013 to November 2016) was obtained using the key words: aging and
      frailty and quality of life. The final reference list includes 44 documents.
      EXPERT OPINION: Childhood cancer survivors are at risk for frailty and less than
      optimal quality of life. Poor emotional health may contribute to this
      association. Further research is needed to better explain these associations and
      to provide a foundation for the development of interventions designed to prevent
      and remediate frail health and suboptimal quality of life in this population.

PMID- 28451646
TI  - Chronotropic Incompetence and Risk of Atrial Fibrillation: The Henry Ford
      ExercIse Testing (FIT) Project.
AB  - OBJECTIVES: To examine the association between chronotropic incompetence and
      incident atrial fibrillation (AF). BACKGROUND: Patients with inadequate heart
      rate response during exercise may have abnormalities in sinus node function or
      autonomic tone that predispose to the development of AF. METHODS: We examined the
      association between heart rate response and incident AF in 57,402 (mean age=54+/
      13 years, 47% female, 64% white) patients free of baseline AF who underwent
      exercise-treadmill stress testing from the Henry Ford ExercIse Testing (FIT)
      Project. Age-predicted maximum heart rate (pMHR) values <85% and chronotropic
      index values <80% were used to define chronotropic incompetence. Cox regression,
      adjusting for demographics, cardiovascular risk factors, medications, coronary
      heart disease, heart failure, and metabolic equivalent of task achieved, was used
      to compute hazard ratios (HR) and 95% confidence intervals (CI) for the
      association between chronotropic incompetence and incident AF. RESULTS: Over a
      median follow-up of 5.0 years (25th-75th percentiles=2.6, 7.8), a total of 3,395
      (5.9%) participants developed AF. pMHR values <85% were associated with an
      increased risk for AF development (HR=1.33, 95%CI=1.22, 1.44). Chronotropic index
      values <80% also were associated with an increased risk of AF (HR=1.28,
      95%CI=1.19, 1.38). The associations of pMHR and chronotropic index with AF
      remained significant with varying cut-off points to define chronotropic
      incompetence. CONCLUSIONS: Our analysis suggests that patients with inadequate
      heart rate response during exercise have an increased risk for developing AF.

PMID- 28451647
TI  - Influence of Oral Progesterone Administration on Drug-Induced QT Interval
      Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.
AB  - OBJECTIVES: We tested the hypothesis that oral progesterone administration
      attenuates drug-induced QT interval lengthening. BACKGROUND: Evidence from
      preclinical and human investigations suggests that higher serum progesterone
      concentrations may be protective against drug-induced QT interval lengthening.
      METHODS: In this prospective, double-blind, crossover study, 19 healthy female
      volunteers (21-40 years) were randomized to receive progesterone 400 mg or
      matching placebo orally once daily for 7 days timed to the menses phase of the
      menstrual cycle (between-phase washout period = 49 days). On day 7, ibutilide
      0.003 mg/kg was infused over 10 minutes, after which QT intervals were recorded
      and blood samples collected for 12 hours. Prior to the treatment phases, subjects
      underwent ECG monitoring for 12 hours to calculate individualized heart rate
      corrected QT intervals (QTcI). RESULTS: Fifteen subjects completed all study
      phases. Maximum serum ibutilide concentrations in the progesterone and placebo
      phases were similar (1247+/-770 vs 1172+/-709 pg/mL, p=0.43). Serum progesterone
      concentrations were higher during the progesterone phase (16.2+/-11.0 vs 1.2+/
      1.0 ng/mL, p<0.0001), while serum estradiol concentrations in the two phases were
      similar (89.3+/-62.8 vs 71.8+/-31.7 pg/mL, p=0.36). Pre-ibutilide lead II QTcI
      was significantly lower in the progesterone phase (412+/-15 vs 419+/-14 ms,
      p=0.04). Maximum ibutilide-associated QTcI (443+/-17 vs 458+/-19 ms, p=0.003),
      maximum percent increase in QTcI from pretreatment value (7.5+/-2.4 vs 9.3+/
      3.4%, p=0.02) and area under the effect (QTcI) curve during the first hour post
      ibutilide (497+/-13 vs 510+/-16 ms-hr, p=0.002) were lower during the
      progesterone phase. Progesterone-associated adverse effects included
      fatigue/malaise and vertigo. CONCLUSIONS: Oral progesterone administration
      attenuates drug-induced QTcI lengthening.

PMID- 28451648
TI  - Necroptosis and Cancer.
AB  - Necroptosis is a programmed lytic cell death pathway, deregulation of which is
      linked to various inflammatory disorders. Escape from programmed cell death and
      inflammation play a significant role in cancer, and therefore, investigating the
      role of necroptosis in cancer has been of high interest. Necroptosis has been
      shown to promote cancer metastasis and T cells death. Escape from necroptosis via
      loss of RIPK3 expression is a feature of some cancers. While necroptosis is a
      promising novel target for cancer therapies, further investigation into its
      biological role in carcinogenesis is warranted. In this article, we review the
      recently-identified interplay points between necroptosis and cancer, and outline
      major biological questions that require further inquiry on the road to targeting
      this pathway in cancer.

PMID- 28451649
TI  - Objective Measures of Visual Function in Papilledema.
AB  - Visual function is an important parameter to consider when managing patients with
      papilledema. Though the current standard of care uses standard automated
      perimetry (SAP) to obtain this information, this test is inherently subjective
      and prone to patient errors. Objective visual function tests including the visual
      evoked potential, pattern electroretinogram, photopic negative response of the
      full field electroretinogram, and pupillary light response have the potential to
      replace or supplement subjective visual function tests in papilledema management.
      This article reviews the evidence for use of objective visual function tests to
      assess visual function in papilledema and discusses future investigations needed
      to develop them as clinically practical and useful measures for this purpose.

PMID- 28451651
TI  - Decreasing Estimated Glomerular Filtration Rate Is Associated With Increased Risk
      of Hospitalization After Kidney Transplantation.
AB  - INTRODUCTION: Following renal transplantation, decreased renal function is
      associated with increased risk of cardiovascular disease, graft loss and
      mortality. We investigated whether declining renal function was associated with
      hospitalization post-transplant. METHODS: Adult, first-time, kidney transplant
      recipients between 2004 and 2006 from the United Network for Organ Sharing
      database and hospitalizations one year after the 6-month post-transplant follow
      up visit were examined. Generalized linear models explored the relationship
      between estimated glomerular filtration rate (eGFR) measured at 6 months and the
      number of hospitalizations in the following year. RESULTS: Of 15,778 kidney
      transplant recipients, 19.1% were admitted in the year after the 6-month follow
      up visit. Among those hospitalized, the mean number of hospitalizations was 1.71
      and increased with decreasing eGFR. In multivariable models, a decrease in eGFR
      was significantly associated with increased hospitalizations: for every 10
      ml/min/1.73m2 decrease in eGFR, there was an 11% increase in hospitalization rate
      (p <0.001). Lower eGFR after the first 6 months following transplantation was
      associated with an increase in late hospitalizations among adult kidney
      transplant recipients. DISCUSSION: Identifying patients with declining eGFR and
      other risk factors may help prevent morbidity and mortality associated with
      hospitalization post-transplantation.

PMID- 28451650
TI  - Lipidomic Signature of Progression of Chronic Kidney Disease in the Chronic Renal
      Insufficiency Cohort.
AB  - INTRODUCTION: Human studies report conflicting results on the predictive power of
      serum lipids on progression of chronic kidney disease (CKD). We aimed to
      systematically identify the lipids that predict progression to end-stage kidney
      disease. METHODS: From the Chronic Renal Insufficiency Cohort, 79 patients with
      CKD stage 2 to 3 who progressed to ESKD over 6 years of follow up were selected
      and frequency-matched by age, sex, race, and diabetes with 121 non-progressors
      with less than 25% decline in estimated glomerular filtration rate (eGFR) during
      the follow up. The patients were randomly divided into Training and Test sets. We
      applied liquid chromatography-mass spectrometry-based lipidomics on visit year 1
      samples. RESULTS: We identified 510 lipids, of which the top 10 coincided with
      false discovery threshold of 0.058 in the Training set. From the top 10 lipids,
      the abundance of diacylglycerols (DAGs) and cholesteryl esters was lower, but
      that of phosphatidic acid 44:4 and monoacylglycerol (MAG) 16:0 was significantly
      higher in progressors. Using logistic regression models a multi-marker panel
      consisting of DAGs, and MAG independently predicted progression. The c-statistic
      of the multimarker panel added to the base model consisting of eGFR and urine
      protein-creatinine ratio (UPCR) as compared to that of the base model was 0.92
      (95% Confidence Interval [CI]: 0.88-0.97), and 0.83 (95% CI: 0.76-0.90, P<0.01),
      respectively; an observation which was validated in the Test subset. CONCLUSION:
      We conclude that a distinct panel of lipids may improve prediction of progression
      of CKD beyond eGFR and UPCR when added to the base model.

PMID- 28451652
TI  - Mental Health in Diabetes Prevention and Intervention Programs in American
      Indian/Alaska Native Communities.
AB  - American Indian and Alaska Natives youth and adults experience higher rates of
      type 2 diabetes and mental health problems than the general United States
      population. Few studies have explored the relationship other than detail the two
      issues independently. The present review aims to identify programs that seek to
      prevent/treat type 2 diabetes and mental health disorders in the American Indian
      and Alaska Native population. Available programs were reviewed for AI/AN adults
      and youth who suffer with both. As part of the review process, databases were
      searched for peer reviewed published studies. It was found that very few programs
      effectively incorporate mental health into the existing diabetes program. Four
      recommendations for future research are offered based on this literature review.

PMID- 28451653
TI  - Designing of blue, green, and red CsPbX3 perovskite-codoped flexible films with
      water resistant property and elimination of anion-exchange for tunable white
      light emission.
AB  - We successfully synthesized blue, green, and red CsPbX3 QDs-codoped flexible
      films using a one-step electrospun strategy, followed by coating a strongly
      hydrophobic silicone resin on the surface of the films. The codoped flexible
      light-emitting films are resistant to water, thereby preventing anion exchange
      and significantly prolonging the lifetime of light emitters under ambient air
      conditions.

PMID- 28451654
TI  - Mimicking multivalent protein-carbohydrate interactions for monitoring the
      glucosamine level in biological fluids and pharmaceutical tablets.
AB  - An easily synthesizable probe has been employed for dual mode sensing of
      glucosamine in pure water. The method was also applied for glucosamine estimation
      in blood serum samples and pharmaceutical tablets. Further, selective detection
      of glucosamine was also achieved using portable color strips.

PMID- 28451655
TI  - Magneto-optically active magnetoplasmonic graphene.
AB  - Two-dimensional nanocomposites with magnetic and optical properties were
      investigated for novel magneto-optical (MO) applications. Such an MO effect could
      be induced and enhanced by synergistic properties with magnetic and plasmonic
      coupling. In this study, magnetoplasmonic graphene (MPGRP) decorated with Au
      nanoparticles (NPs) and magnetic NPs (MNPs) was simply prepared as a 2D MO active
      material. This MPGRP exhibited superparamagnetic behaviour at room temperature
      and strong MO activity, resulting from magnetic spin from the MNPs and electron
      spin from the Au NPs on one graphene sheet, which is beneficial for memory or
      optoelectronic devices, sensing platforms, energy harvesting, and biomedical MO
      devices.

PMID- 28451656
TI  - Interactions of ionic liquids and surfaces of graphene related nanoparticles
      under high pressures.
AB  - High-pressure infrared spectroscopy was used to study the interactions between 1
      methyl-3-propylimidazolium iodide [MPIM]I and graphene-based nanoparticles. The
      results obtained at ambient pressure indicate the imidazolium ring of the cation
      to be a more favorable moiety for adsorption than alkyl C-H groups at ambient
      pressure. Upon increasing the pressure, the dominant C2-H band of pure [MPIM]I
      yields a significant red frequency shift. As the mixtures, i.e., graphene oxide
      (GO)/[MPIM]I, reduced graphene oxide (RGO)/[MPIM]I, and graphene (G)/[MPIM]I,
      were compressed, mild shifts in the C2-H absorption frequency were observed. The
      absence of drastic red-shifts suggests that the local C2-H structures may be
      perturbed by the addition of GO, RGO, and G under high pressures. When pure
      [MPIM]I was compressed from ambient to 0.4 GPa, the alkyl C-H band at ca. 2964 cm
      1 was blue-shifted to 2984 cm-1. This discontinuous jump occurring around 0.4 GPa
      becomes less obvious for the mixtures GO/[MPIM]I, RGO/[MPIM]I, and G/[MPIM]I. The
      results of this study suggest that the addition of GO, RGO, and G can disturb the
      local structures of alkyl C-H under high pressures, demonstrating that high
      pressures may have the potential to tune the strength of ionic liquid-surface
      interactions and the performance of energy storage devices (e.g.
      supercapacitors).

PMID- 28451657
TI  - Tuning the upconversion light emission by bandgap engineering in bismuth oxide
      based upconverting nanoparticles.
AB  - In the field of novel applications involving upconverting processes, the
      determination of new strategies for realizing emission-tunable nanomaterials is a
      challenge. In this work the design of Y3+ and Er3+ codoped bismuth oxide-based
      upconverting nanoparticles is presented, evidencing that the active role of the
      matrix allows for the emission selectivity with chromaticity control. The bandgap
      of the bismuth oxide-based host can be manipulated in the range of 0.65 eV,
      consequently leading to upconversion emission color tunability from red to yellow
      greenish. The resulting fine control of the nanoparticle chromaticity through
      accurate host bandgap engineering reveals a novel concept for the development of
      a new generation of upconverting nanophosphors.

PMID- 28451658
TI  - Transformation from single-mesoporous to dual-mesoporous organosilica
      nanoparticles.
AB  - Transformation from single-mesoporous to dual-mesoporous structured organosilica
      nanoparticles can be achieved by simply varying the volume fraction of ethanol in
      the synthesis system, using lauryl sulfonate betaine and sodium dodecyl sulfonate
      as dual-templates. Core-shell structured dual-mesoporous organosilica
      nanoparticles possess smaller mesopores (4.0 nm) in the shell and flower-like
      larger mesopores (46 nm) in the core. Owing to the unique mesostructure, dual
      mesoporous organosilica nanoparticles show a high loading capacity and a slow
      release rate for cargo molecules. The large mesopores on the inside can provide a
      large storage space for the guest molecules and the small mesopores in the outer
      shell act as a natural valve, slowing the release. In addition, both single
      mesoporous and dual-mesoporous organosilica nanoparticles, exhibit low cell
      toxicity and excellent cell permeability.

PMID- 28451659
TI  - The behavior of a paramagnetic system in electric and magnetic fields as
      exemplified by revisiting Li@B10H14.
AB  - The electric and magnetic properties of the Li@B10H14 complex, considered as a
      novel inorganic electride-type system with potential for second-order non-linear
      optical (NLO) applications, have already been studied. However, the reported C2v
      structure is not the global energy minimum and therefore its electronic and
      magnetic properties need to be revisited. Moreover, by applying more accurate
      computational protocols (ROHF-CCSD/CCSD(T) and larger basis sets) we show that
      the model chemistry used earlier (UMP2/6-31+G(d)) is not sufficient for reliable
      description of the NLO responses of this open-shell doublet complex. The global
      minimum based on the Cs symmetry is significantly (by ca. 25 kcal mol-1) more
      stable than the C2v structure and it should be viewed as a system with moderate
      NLO responses. An excess of unpaired electron density is also responsible for the
      contact and pseudo-contact contributions to the magnetic properties, which was
      not considered in the earlier work.

PMID- 28451660
TI  - Impact and consequences of polyphenols and fructooligosaccharide interplay on gut
      microbiota in rats.
AB  - Both fructooligosaccharide (FOS) and polyphenols can be individually and directly
      transferred to the large intestine of mammals and are beneficial for human health
      as they reshape the composition of gut microbiota. The combination impact of FOS
      and polyphenols on rats' gut microbiota and the corresponding consequences on
      rats were investigated via MiSeq sequencing technique and bioinformatics. The
      results showed that the combination of different phenolic compounds and FOS
      displayed distinct impact on the host. The addition of catechin to a FOS diet
      inhibited Firmicutes and enhanced Bacteroidetes. Moreover, the content of each
      short chain fatty acid fluctuated in various groups because different unique
      bacterial species survived or were inhibited under three conditions. On the other
      aspects, the supplement of catechin controlled the body weight (BW), up-regulated
      serum leptin, induced more soluble carbohydrates and less soluble polysaccharides
      in feces, and inhibited or activated some specific genera. The inhibition of
      genera by catechin could be responsible for the degradation of carbohydrates in
      gut and the activation of genera might be keystones for the increment of serum
      leptin. The effect of consuming FOS and/or polyphenols on the health of hosts
      needs to be further explored.

PMID- 28451661
TI  - Observation of short range ferromagnetic interactions and magnetocaloric effect
      in cobalt substituted Gd5Si2Ge2.
AB  - We report on the observation of double transition - a first order and a second
      order transition in Gd5Si2-xCoxGe2 with x = 0, 0.1, 0.2 and 0.4 with the
      appearance of short-range ferromagnetic correlations. The first order phase
      transition is due to a combined magnetostructural transition from monoclinic
      paramagnetic phase to orthorhombic ferromagnetic phase on cooling while the
      second order transition arises from an orthorhombic paramagnetic to ferromagnetic
      phase on cooling. Structural studies show that the substituted compounds
      crystallize in a combination of Gd5Si2Ge2 and Gd5Si4 phases. Low-temperature X
      ray diffraction measurements confirm the complete transformation from monoclinic
      to orthorhombic phase. DC magnetization measurements reveal an anomalous low
      field magnetic behaviour indicating a Griffiths-like phase. This unusual
      behaviour is attributed to the local disorder within the crystallographic
      structure indicating the presence of short-range magnetic correlations and
      ferromagnetic clustering, which is stabilized and enhanced by competing intra
      layer and inter-layer magnetic interactions. The magnetostructural transition
      results in entropy changes (-DeltaSM) of 9 J kg-1 K-1 at 260 K for x = 0.1, 8.5 J
      kg-1 K-1 at 245 K for x = 0.2 and 4.2 J kg-1 K-1 at 210 K for x = 0.4 for a field
      change of 50 kOe. Co substitution induces compelling crystallographic and
      magnetoresponsive effects in the Gd-Si-Ge system, which could be useful for
      potential and smart applications such as solid-state magnetic refrigeration and
      sensitive magnetic switching from paramagnetic to ferromagnetic state. Universal
      curve analysis has been carried out on the substituted samples to study the order
      of the magnetic transition.

PMID- 28451662
TI  - Is an electric field always a promoter of wetting? Electro-dewetting of metals by
      electrolytes probed by in situ X-ray nanotomography.
AB  - We developed a special electrochemical cell enabling quantitative analysis and in
      situ X-ray nanotomography of metal/electrolyte interfaces subject to corrosion.
      Using this cell and applying the nodoid model to describe menisci formed on
      tungsten wires during anodization, the evolution of the electrolyte surface
      tension, the concentration of reaction products, and the meniscus contact angle
      were studied. In contrast to the electrowetting effect, where the applied
      electric field decreases the contact angle of electrolytes, anodization of the
      tungsten wires increases the contact angle of the meniscus. Hence, an electric
      field favors dewetting rather than wetting of the newly formed surface. The
      discovered effect opens up new opportunities for the control of wetting phenomena
      and calls for the revision of existing theories of electrowetting.

PMID- 28451663
TI  - The effect of Isabel grape addition on the physicochemical, microbiological and
      sensory characteristics of probiotic goat milk yogurt.
AB  - Goat milk is an attractive food because of its nutritional properties, easy
      digestibility and hypoallergenicity. Goat milk yogurt is an appropriate matrix
      for the inclusion of new ingredients such as probiotic cultures, fruit and its
      derivatives. Grapes are rich in polyphenols and recognized for their health
      benefits. The aim of this study was to improve the quality characteristics of
      probiotic goat milk yogurt by the addition of an Isabel grape (Vitis labrusca L.)
      preparation (IGP). For this, the influence of the addition of IGP on the
      physicochemical, microbiological and sensory characteristics of goat milk yogurt
      containing the probiotic Lactobacillus acidophilus LA-05 was evaluated during 28
      days of refrigerated storage (5 +/- 0.5  degrees C). Four yogurt formulations
      were prepared, each varying in the added IGP amount, as follows: Y0 (not
      containing IGP), YG15 (containing 15 g per 100 mL of IGP), YG20 (containing 20 g
      per 100 mL of IGP), and YG25 (containing 25 g per 100 mL of IGP). All
      formulations showed probiotic counts ranging from 7 to 8 log CFU mL-1 over the
      assessed storage period. The addition of 20 g per 100 mL of IGP affected
      positively the colour, viscosity, and sensory acceptance of the yogurt
      formulations. The production of goat milk yogurt containing L. acidophilus LA-05
      and IGP is an option for developing a new goat dairy product with added value due
      to the inclusion of components with potential functional properties.

PMID- 28451664
TI  - Investigation of surface energies in spin crossover nanomaterials: the role of
      surface relaxations.
AB  - We analyse in detail the role of surface relaxations on the spin transition
      phenomenon through an Ising-like model solved in the inhomogeneous mean field
      approach. We show the surface relaxation tends to decrease the energy cost of
      missing bonds. Cooperative phenomena are also affected, leading to an asymmetric
      hysteresis loop. The underlying mechanisms are investigated by calculating
      thermodynamics excess quantities. Far from the spin transition, the contribution
      of surface relaxations to the excess internal energy, entropy and free energy is
      negligible, but their role becomes substantial around the transition temperature.

PMID- 28451665
TI  - Photocatalytic radical cyclization of alpha-halo hydrazones with beta
      ketocarbonyls: facile access to substituted dihydropyrazoles.
AB  - A mild and efficient method for the photocatalytic radical cyclization of alpha
      halo hydrazones with beta-ketocarbonyls has been described. This strategy
      provides a potential protocol for the construction of functionalized 4,5
      dihydropyrazoles in moderate to high yields.

PMID- 28451666
TI  - Transition metal-free C(sp3)-H bond coupling among three methyl groups.
AB  - A coupling of multiple C(sp3)-H bonds of the methyl group in methyl ketones with
      dimethyl sulfoxide is developed. This coupling allows the direct C(sp3)-H bond
      coupling among three methyl groups and affords one C-C bond and one C[double
      bond, length as m-dash]C bond under transition metal-free conditions. The value
      added cyclized 3-methylthiomethyl chroman-4-ones can be synthesized through this
      method. A plausible mechanism is proposed.

PMID- 28451667
TI  - Potassium adsorption behavior on hcp cobalt as model systems for the Fischer
      Tropsch synthesis: a density functional theory study.
AB  - Potassium (K), an important impurity in syngas from biomass, can have a large
      influence on the activity and selectivity of cobalt-based Fischer-Tropsch
      synthesis (FTS) catalysts in Biomass to Liquids (BTL) processes. In this work,
      the potassium adsorption behavior on hcp cobalt was systematically studied using
      density functional theory. The surface energy calculations and Wulff construction
      of the equilibrium shape of hcp cobalt showed it is dominated by 10 facets. The
      interaction of K with these facets has been investigated. The results showed that
      the stepped facet (10-12) has the highest K adsorption energy of -2.40 eV. The
      facets (0001), (10-10), (10-11), (10-15), and (21-30) also showed relatively high
      K adsorption energies in the range of -2.28 to -2.34 eV. The corrugated facets
      exhibited comparatively lower K adsorption energies (-2.04 to -2.18 eV), and
      would be less favorable for K adsorption. It was also found that the adsorption
      properties depend on coverage, where the K adsorption energy decreased with
      increasing coverage. Diffusion energy barrier calculations indicated that K was
      mobile on typical facets (0001) and (10-11) with very low diffusion barriers
      (<0.15 eV). On stepped facets, although K could move freely along the same step
      (diffusion barrier <0.01 eV), diffusion from one step to another had a
      significantly higher barrier of 0.56 eV. This suggested that K atoms would be
      mobile to some extent during FTS reaction conditions, and tend to occupy the most
      favorable sites independent of their initial position. The results obtained in
      this work provide valuable information on the interaction of K with cobalt
      surfaces, relevant for practical cobalt catalysts and their application in BTL
      processes.

PMID- 28451668
TI  - S,N co-doped carbon nanotubes decorated with ultrathin molybdenum disulfide
      nanosheets with highly electrochemical performance.
AB  - A facile route for the synthesis of a type of composite nanotube, namely S,N co
      doped carbon nanotubes decorated with molybdenum disulfide nanosheets (CP/MoS2),
      is now reported. The number of nanosheets for MoS2 can be easily tuned by
      changing the templates with different ratios of N and S. When evaluated as an
      anode material for lithium-ion batteries, the CP/MoS2 nanotubes show a high
      specific capacity of around 1500 mA h g-1 at the current density of 50 mA g-1,
      excellent cycling stability up to 750 cycles at the current density of 1 A g-1,
      and superior rate performance.

PMID- 28451669
TI  - A sensitive fluorescent probe for the polar solvation dynamics at protein
      surfactant interfaces.
AB  - Relaxation dynamics at the surface of biologically important macromolecules is
      important taking into account their functionality in molecular recognition. Over
      the years it has been shown that the solvation dynamics of a fluorescent probe at
      biomolecular surfaces and interfaces account for the relaxation dynamics of polar
      residues and associated water molecules. However, the sensitivity of the dynamics
      depends largely on the localization and exposure of the probe. For noncovalent
      fluorescent probes, localization at the region of interest in addition to surface
      exposure is an added challenge compared to the covalently attached probes at the
      biological interfaces. Here we have used a synthesized donor-acceptor type
      dipolar fluorophore, 6-acetyl-(2-((4-hydroxycyclohexyl)(methyl)amino)naphthalene)
      (ACYMAN), for the investigation of the solvation dynamics of a model protein
      surfactant interface. A significant structural rearrangement of a model histone
      protein (H1) upon interaction with anionic surfactant sodium dodecyl sulphate
      (SDS) as revealed from the circular dichroism (CD) studies is nicely corroborated
      in the solvation dynamics of the probe at the interface. The polarization gated
      fluorescence anisotropy of the probe compared to that at the SDS micellar surface
      clearly reveals the localization of the probe at the protein-surfactant
      interface. We have also compared the sensitivity of ACYMAN with other solvation
      probes including coumarin 500 (C500) and 4-(dicyanomethylene)-2-methyl-6-(p
      dimethylamino-styryl)-4H-pyran (DCM). In comparison to ACYMAN, both C500 and DCM
      fail to probe the interfacial solvation dynamics of a model protein-surfactant
      interface. While C500 is found to be delocalized from the protein-surfactant
      interface, DCM becomes destabilized upon the formation of the interface (protein
      surfactant complex). The timescales obtained from this novel probe have also been
      compared with other femtosecond resolved studies and molecular dynamics
      simulations.

PMID- 28451670
TI  - Tunnelling and barrier-less motions in the 2-fluoroethanol-water complex: a
      rotational spectroscopic and ab initio study.
AB  - The pure rotational spectrum of the 2-fluoroethanol (2-FE)water complex was
      measured using a chirped pulse Fourier-transform microwave spectrometer and a
      cavity-based Fourier-transform microwave spectrometer. In the detected 2-FEwater
      conformer, 2-FE serves as a proton donor, in contrast to its role in the observed
      ethanolwater conformer, while water acts simultaneously as a hydrogen bond donor
      and acceptor, forming a hydrogen-bonded ring with an OHO and an OHF hydrogen
      bond. Comparison to the calculated dipole moment components suggests that the
      observed structure sits between the two most stable minima identified
      theoretically. This conclusion is supported by extensive deuterium isotopic data.
      Further analysis shows that these two minima are connected by a barrier-less
      wagging motion of the non-bonded hydrogen of the water subunit. The observed
      narrow splitting with a characteristic 3 : 1 intensity ratio is attributed to an
      exchange of the bonded and non-bonded hydrogen atoms of water. The tunneling
      barrier of a proposed tunneling path is calculated to be as low as 5.10 kJ mol-1.
      A non-covalent interaction analysis indicates that the water rotation motion
      along the tunneling path has a surprisingly small effect on the interaction
      energy between water and 2-FE.

PMID- 28451671
TI  - Defect-promoted photo-electrochemical performance enhancement of orange
      luminescent ZnO nanorod-arrays.
AB  - Intentionally defect-rich zinc oxide (ZnO) nanorod-arrays were grown from
      solution by carefully adjusting the concentration ratio of the growth-precursors
      used followed by various post-deposition thermal treatments. Post-deposition
      rapid thermal annealing (RTA) at moderate temperatures (350  degrees C-550 
      degrees C) and in various atmospheres was applied to vary the defect composition
      of the grown nanorod-arrays. It is demonstrated that, intense, defect-related
      orange emission occurs solely upon RTA around 450  degrees C and is essentially
      independent of the atmosphere used. Extensive materials characterization was
      carried out in order to evaluate the origin of the orange-luminescent defects and
      what influence they have on the ZnO material properties. It is concluded that the
      oxygen vacancy-zinc interstitial defect complex (VO-Zni) is responsible for the
      orange luminescence in the prepared materials. A kinetic formation mechanism of
      the VO-Zni complex dependent on the RTA temperature is proposed and shown to be
      in accordance with the experimental findings. Furthermore it is shown that this
      bulk deep-level defect could act as a trap state for photo-generated electrons
      prolonging the charge carrier lifetime of photo-generated holes and therefore
      improving the charge carrier separation in the material. As a result the photo
      current density under simulated sunlight is found to increase by almost 150% over
      as-grown samples. The potential use of this defective material in applications
      such as solar water splitting is outlined.

PMID- 28451672
TI  - Microencapsulation through thermally sintering Pickering emulsion-based
      colloidosomes.
AB  - Microcapsules of a phase change material synthesized by thermally sintering
      Pickering emulsion-based colloidosomes were demonstrated. The protocol included
      three steps: (1) monodispersive poly(glycidyl methacrylate) (PGMA) microspheres
      were prepared by dispersive polymerization and were endowed with a contact angle
      of 63.4 degrees  for oil-in-water Pickering stabilization by hydrolysis. (2) By
      phase separation during Pickering emulsion polymerization, microcapsules with a
      structure of a single PCM core and a PGMA armored polystyrene shell were
      fabricated. (3) Thermal sintering was performed to fuse the polystyrene and PGMA
      microspheres into an integral shell of the microcapsules. The durability of the
      microcapsules before and after sintering was investigated by a suspension test
      (in water and ethanol) and an accelerated thermal cycling test. The sintering
      reduced the percentage of leaked dodecanol from 19.6% to 10.3% in the suspension
      test in ethanol and from 10.4% to 2.8% in the accelerated cycling test. These
      results verified that the sintering process endowed the prepared microcapsules
      with better tightness and durability.

PMID- 28451673
TI  - Enzyme-MOF (metal-organic framework) composites.
AB  - The ex vivo application of enzymes in various processes, especially via enzyme
      immobilization techniques, has been extensively studied in recent years in order
      to enhance the recyclability of enzymes, to minimize enzyme contamination in the
      product, and to explore novel horizons for enzymes in biomedical applications.
      Possessing remarkable amenability in structural design of the frameworks as well
      as almost unparalelled surface tunability, Metal-Organic Frameworks (MOFs) have
      been gaining popularity as candidates for enzyme immobilization platforms. Many
      MOF-enzyme composites have achieved unprecedented results, far outperforming free
      enzymes in many aspects. This review summarizes recent developments of MOF-enzyme
      composites with special emphasis on preparative techniques and the synergistic
      effects of enzymes and MOFs. The applications of MOF-enzyme composites, primarily
      in transferation, catalysis and sensing, are presented as well. The enhancement
      of enzymatic activity of the composites over free enzymes in biologically
      incompatible conditions is emphasized in many cases.

PMID- 28451674
TI  - Oscillatory rheology of dense, athermal suspensions of nearly hard spheres below
      the jamming point.
AB  - The viscosity of a dense suspension has contributions from hydrodynamics and
      particle interactions, both of which depend upon the flow-induced arrangement of
      particles into fragile structures. Here, we study the response of nearly hard
      sphere suspensions to oscillatory shear using simulations and experiments in the
      athermal, non-inertial limit. Three distinct regimes are observed as a function
      of the strain amplitude gamma0. For gamma0 < 10-1, initially non-contacting
      particles remain separated and the suspension behaves similarly to a Newtonian
      fluid, with the shear stress proportional to the strain rate, and the normal
      stresses close to zero. For gamma0 > 101, the microstructure becomes well
      established at the beginning of each shear cycle and the rheology is quasi
      Newtonian: the shear stress varies with the rate, but flow-induced structures
      lead to non-zero normal stresses. At intermediate gamma0, particle-particle
      contacts break and reform across entire oscillatory cycles, and we probe a non
      linear regime that reveals the fragility of the material. Guided by these
      features, we further show that oscillatory shear may serve as a diagnostic tool
      to isolate specific stress contributions in dense suspensions, and more generally
      in those materials whose rheology has contributions with both hydrodynamic and
      non-hydrodynamic origin.

PMID- 28451675
TI  - CoNi2Se4 as an efficient bifunctional electrocatalyst for overall water
      splitting.
AB  - CoNi2Se4 with a vacancy-ordered spinel structure shows excellent bifunctional
      electrocatalytic activity for water splitting in alkaline medium producing 10 mA
      cm-2 at a cell voltage of 1.61 V. For OER, an overpotential of 160 mV was needed
      for 10 mA cm-2 which is one of the lowest overpotentials reported to date.

PMID- 28451676
TI  - Unravelling the mysteries of sub-second biochemical processes using time-resolved
      mass spectrometry.
AB  - Many important chemical and biochemical phenomena proceed on sub-second time
      scales before entering equilibrium. In this mini-review, we explore the history
      and recent advancements of time-resolved mass spectrometry (TRMS) for the
      characterization of millisecond time-scale chemical reactions and biochemical
      processes. TRMS allows for the simultaneous tracking of multiple reactants,
      intermediates and products with no chromophoric species required, high
      sensitivity and temporal resolution. The method has most recently been used for
      the characterization of several short-lived reaction intermediates in rapid
      chemical reactions. Most of the reactions that occur in living organisms are
      accelerated by enzymes, with pre-steady state kinetics only attainable using time
      resolved methods. TRMS has been increasingly used to monitor the conversion of
      substrates to products and the resulting changes to the enzyme during catalytic
      turnover. Early events in protein folding systems have also been elucidated,
      along with the characterization of dynamics and transient secondary structures in
      intrinsically disordered proteins. In this review, we will highlight
      representative examples where TRMS has been applied to study these phenomena.

PMID- 28451677
TI  - An optically-gated AuNP-DNA protonic transistor.
AB  - Bio-interface transistors, which manipulate the transportation of ions (i.e.
      protons), play an important role in bridging physical devices with biological
      functionalities, because electrical signals are carried by ions/protons in
      biological systems. All available ionic transistors use electrostatic gates to
      tune the ionic carrier density, which requires complicated interconnect wires. In
      contrast, an optical gate, which offers the advantages of remote control as well
      as multiple light wavelength selections, has never been explored for ionic
      devices. Here, we demonstrate a light-gated protonic transistor fabricated from
      an Au nanoparticle and DNA (AuNP-DNA) hybrid membrane. The device can be turned
      on and off completely by using light, with a high on/off current ratio of up to 2
      orders of magnitude. Moreover, the device only responds to specific light
      wavelengths due to the plasmonic effect from the AuNPs, which enables the
      capability of wavelength selectivity. Our results open up new avenues for
      exploring remotely controlled ionic circuits, in vivo protonic switches, and
      other biomedical applications.

PMID- 28451678
TI  - A novel luminescent Pb(ii) - organic framework exhibiting a rapid and selective
      detection of trace amounts of NACs and Fe3+ with excellent recyclability.
AB  - A novel three-dimensional metal organic framework, Pb3O2L (1) (H2L = 4-(1H
      tetrazol-5-yl)phenol), with a unique 3D network structure exhibits excellent
      luminescence and good stability in water and other organic solvents. 1 can act as
      a promising dual functional sensor for the detection and recognition of
      nitroaromatic explosives (NACs) and Fe3+ ions via fluorescence quenching with
      high selectivity and sensitivity in an aqueous phase. Importantly, 1 as a
      fluorescent sensor of Fe3+ can be simply and quickly regenerated, which
      represents a rare example of a reported luminescent sensor of Fe3+ ions.
      Furthermore, the visible colour changes in the detection process make them easy
      to distinguish by the naked eyes, and luminescent test plates broaden its
      potential application in detection of Fe3+ ions. Experimental and theoretical
      calculations indicate that the luminescence quenching can be attributed to an
      electron and resonance energy transfer between the MOF and analytes. The present
      study contributes to the development of MOF materials research, specifically in
      their application as biological and environmental fluorescent sensors.

PMID- 28451679
TI  - A DNA-gold nanoparticle hybrid hydrogel network prepared by enzymatic reaction.
AB  - We report a DNA-gold nanoparticle (AuNP) hybrid hydrogel in which the AuNPs
      crosslink enzymatically synthesized DNA to form a gel network. PCR-elongated DNA
      and AuNPs act as a one-dimensional polymer and cross-linkers, respectively. The
      DNA-AuNP hydrogel has the functional properties of both long DNA and the AuNPs.

PMID- 28451680
TI  - A mechanically enhanced hybrid nano-stratified barrier with a defect suppression
      mechanism for highly reliable flexible OLEDs.
AB  - Understanding the mechanical behaviors of encapsulation barriers under bending
      stress is important when fabricating flexible organic light-emitting diodes
      (FOLEDs). The enhanced mechanical characteristics of a nano-stratified barrier
      were analyzed based on a defect suppression mechanism, and then experimentally
      demonstrated. Following the Griffith model, naturally-occurring cracks, which
      were caused by Zn etching at the interface of the nano-stratified structure, can
      curb the propagation of defects. Cross-section images after bending tests
      provided remarkable evidence to support the existence of a defect suppression
      mechanism. Many visible cracks were found in a single Al2O3 layer, but not in the
      nano-stratified structure, due to the mechanism. The nano-stratified structure
      also enhanced the barrier's physical properties by changing the crystalline phase
      of ZnO. In addition, experimental results demonstrated the effect of the
      mechanism in various ways. The nano-stratified barrier maintained a low water
      vapor transmission rate after 1000 iterations of a 1 cm bending radius test.
      Using this mechanically enhanced hybrid nano-stratified barrier, FOLEDs were
      successfully encapsulated without losing mechanical or electrical performance.
      Finally, comparative lifetime measurements were conducted to determine
      reliability. After 2000 hours of constant current driving and 1000 iterations
      with a 1 cm bending radius, the FOLEDs retained 52.37% of their initial
      luminance, which is comparable to glass-lid encapsulation, with 55.96% retention.
      Herein, we report a mechanically enhanced encapsulation technology for FOLEDs
      using a nano-stratified structure with a defect suppression mechanism.

PMID- 28451681
TI  - Ordered assembly of hybrid room-temperature phosphorescence thin films showing
      polarized emission and the sensing of VOCs.
AB  - Benefitting from the self-organization of organic phosphors into 2D galleries of
      clay nanosheets, we have developed a method for the ordered assembly of long
      lived room-temperature phosphorescence (RTP) thin films through a layer-by-layer
      (LBL) process. The clay-based thin films present polarized RTP and serve as
      sensors for VOCs.

PMID- 28451682
TI  - Unexpected catalytic activity of simple triethylborohydrides in the
      hydrosilylation of alkenes.
AB  - The first example of sodium triethylborohydride-catalysed hydrosilylation of
      alkenes is reported. The hydrosilylation of certain alkenes, in particular
      styrenes, vinylsilanes and allyl glycidyl ether, with aromatic hydrosilanes
      proceeded in a highly regioselective manner to give Markovnikov products. It is
      significant that several protocols use NaHBEt3 as a reducing agent generating
      active catalysts in situ of other hydrosilylation reactions. An anionic mechanism
      of hydrosilylation is proposed.

PMID- 28451683
TI  - Reversible conversion between a pleated oligo-tetrathiafulvalene radical foldamer
      and folded donor-acceptor [3]pseudorotaxane under redox conditions.
AB  - Linear tetrathiafulvalene (TTF) oligomers were synthesized, which could not only
      form a pleated TTF+ radical cation foldamer under oxidation conditions, but also
      interlocked with CBPQT4+ to form folded donor-acceptor [3]pseudorotaxane in the
      neutral state of TTF. Moreover, switchable transformation between these two
      folded supramolecular structures was achieved under the alternative regulation of
      the redox states of TTF units.

PMID- 28451684
TI  - Effects of early enteral nutrition supplemented with collagen peptides on post
      burn inflammatory responses in a mouse model.
AB  - The effect of early enteral nutrition (EN) supplemented with Alaska pollock skin
      derived collagen peptides (CPs) on post-burn inflammatory responses was
      investigated in a mouse model. Male blab/c mice were randomly assigned to four
      groups: a sham burn (SB) group, a control group (burn + EN + glycine, BE), a
      positive control group (burn + EN + glutamine, BEG) and a treatment group (burn +
      EN + CPs, BEC). Burn-induced increases of serum endotoxin level, and systemic and
      intestinal concentration of TNF-alpha and IL-6 were attenuated in BEG and BEC at
      post-burn day (PBD) 1, 3 and 7 (p < 0.05 vs. BE). Notably, BEC revealed a
      prominent decrease of the serum endotoxin level, TNF-alpha and IL-6 as compared
      to BEG at PBD 7 (p < 0.05). Furthermore, EN supplemented with CPs diminished the
      phosphorylation of intestinal NF-kappaB p65 and simultaneously down-regulated the
      mRNA expression of TNF-alpha and IL-6 in small intestine (p < 0.05 vs. BE). Also,
      it demonstrated a comparable effect with glutamine in ameliorating post-burn
      inflammatory responses in mice with burns. Therefore, CPs could be considered as
      a potential immunonutrient supplement in EN to improve post-burn outcomes in burn
      patients.

PMID- 28451685
TI  - 2,2,2-Trifluoroethanol as a solvent to control nucleophilic peptide arylation.
AB  - The SNAr arylation of peptides with perfluoroaromatics provides a route by which
      to install a useful chemical handle that enables both 19F-NMR analysis and
      further chemical modification. However, chemo-selective arylation in peptides
      containing multiple nucleophilic side chains currently presents a challenge to
      the field. Herein, we demonstrate that employing 2,2,2-trifluoroethanol (TFE) as
      a solvent in peptide SNAr reactions significantly improves nucleophile
      selectivity when compared to N,N'-dimethylformamide (DMF).

PMID- 28451686
TI  - Data Requirements for the Correct Identification of Medication Errors and Adverse
      Drug Events in Patients Presenting at an Emergency Department.
AB  - BACKGROUND: Adverse drug events (ADE) involving or not involving medication
      errors (ME) are common, but frequently remain undetected as such. Presently, the
      majority of available clinical decision support systems (CDSS) relies mostly on
      coded medication data for the generation of drug alerts. It was the aim of our
      study to identify the key types of data required for the adequate detection and
      classification of adverse drug events (ADE) and medication errors (ME) in
      patients presenting at an emergency department (ED). METHODS: As part of a
      prospective study, ADE and ME were identified in 1510 patients presenting at the
      ED of an university teaching hospital by an interdisciplinary panel of
      specialists in emergency medicine, clinical pharmacology and pharmacy. For each
      ADE and ME the required different clinical data sources (i.e. information items
      such as acute clinical symptoms, underlying diseases, laboratory values or ECG)
      for the detection and correct classification were evaluated. RESULTS: Of all 739
      ADE identified 387 (52.4%), 298 (40.3%), 54 (7.3%), respectively, required one,
      two, or three, more information items to be detected and correctly classified.
      Only 68 (10.2%) of the ME were simple drug-drug interactions that could be
      identified based on medication data alone while 381 (57.5%), 181 (27.3%) and 33
      (5.0%) of the ME required one, two or three additional information items,
      respectively, for detection and clinical classification. CONCLUSIONS: Only 10% of
      all ME observed in emergency patients could be identified on the basis of
      medication data alone. Focusing electronic decisions support on more easily
      available drug data alone may lead to an under-detection of clinically relevant
      ADE and ME.

PMID- 28451687
TI  - Reconstruction of 12-lead ECG Using a Single-patch Device.
AB  - OBJECTIVES: The aim of this study is to develop an optimal electrode system in
      the form of a small and wearable single-patch ECG monitoring device that allows
      for the faithful reconstruction of the standard 12-lead ECG. METHODS: The
      optimized universal electrode positions on the chest and the personalized
      transformation matrix were determined using linear regression as well as
      artificial neural networks (ANNs). A total of 24 combinations of 4 neighboring
      electrodes on 35 channels were evaluated on 19 subjects. Moreover, we analyzed
      combinations of three electrodes within the four-electrode combination with the
      best performance. RESULTS: The mean correlation coefficients were all higher than
      0.95 in the case of the ANN method for the combinations of four neighboring
      electrodes. The reconstructions obtained using the three and four sensing
      electrodes showed no significant differences. The reconstructed 12-lead ECG
      obtained using the ANN method is better than that using the MLR method.
      Therefore, three sensing electrodes and one ground electrode (forming a square)
      placed below the clavicle on the left were determined to be suitable for ensuring
      good reconstruction performance. CONCLUSIONS: Since the interelectrode distance
      was determined to be 5 cm, the suggested approach can be implemented in a single
      patch device, which should allow for the continuous monitoring of the standard 12
      lead ECG without requiring limb contact, both in daily life and in clinical
      practice.

PMID- 28451688
TI  - Boosting Quality Registries with Clinical Decision Support Functionality*. User
      Acceptance of a Prototype Applied to HIV/TB Drug Therapy.
AB  - BACKGROUND: The care of HIV-related tuberculosis (HIV/TB) is complex and
      challenging. Clinical decision support (CDS) systems can contribute to improve
      quality of care, but more knowledge is needed on factors determining user
      acceptance of CDS. OBJECTIVES: To analyze physicians' and nurses' acceptance of a
      CDS prototype for evidence-based drug therapy recommendations for HIV/TB
      treatment. METHODS: Physicians and nurses were involved in designing a CDS
      prototype intended for future integration with the Swedish national HIV quality
      registry. Focus group evaluation was performed with ten nurses and four
      physicians, respectively. The Unified Theory of Acceptance and Use of Technology
      (UTAUT) was used to analyze acceptance. RESULTS: We identified several potential
      benefits with the CDS prototype as well as some concerns that could be addressed
      by redesign. There was also concern about dependence on physician attitudes, as
      well as technical, organizational, and legal issues. CONCLUSIONS: Acceptance
      evaluation at a prototype stage provided rich data to improve the future design
      of a CDS prototype. Apart from design and development efforts, substantial
      organizational efforts are needed to enable the implementation and maintenance of
      a future CDS system.

PMID- 28451689
TI  - A Randomized Trial Comparing Classical Participatory Design to VandAID, an
      Interactive CrowdSourcing Platform to Facilitate User-centered Design.
AB  - BACKGROUND: Early involvement of stakeholders in the design of medical software
      is particularly important due to the need to incorporate complex knowledge and
      actions associated with clinical work. Standard user-centered design methods
      include focus groups and participatory design sessions with individual
      stakeholders, which generally limit user involvement to a small number of
      individuals due to the significant time investments from designers and end users.
      OBJECTIVES: The goal of this project was to reduce the effort for end users to
      participate in co-design of a software user interface by developing an
      interactive web-based crowdsourcing platform. METHODS: In a randomized trial, we
      compared a new web-based crowdsourcing platform to standard participatory design
      sessions. We developed an interactive, modular platform that allows responsive
      remote customization and design feedback on a visual user interface based on user
      preferences. The responsive canvas is a dynamic HTML template that responds in
      real time to user preference selections. Upon completion, the design team can
      view the user's interface creations through an administrator portal and download
      the structured selections through a REDCap interface. RESULTS: We have created a
      software platform that allows users to customize a user interface and see the
      results of that customization in real time, receiving immediate feedback on the
      impact of their design choices. Neonatal clinicians used the new platform to
      successfully design and customize a neonatal handoff tool. They received no
      specific instruction and yet were able to use the software easily and reported
      high usability. CONCLUSIONS: VandAID, a new web-based crowdsourcing platform, can
      involve multiple users in user-centered design simultaneously and provides means
      of obtaining design feedback remotely. The software can provide design feedback
      at any stage in the design process, but it will be of greatest utility for
      specifying user requirements and evaluating iterative designs with multiple
      options.

PMID- 28451690
TI  - Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa
      and X/Xa, emicizumab, depends on its ability to bridge the antigens.
AB  - Emicizumab, a humanised bispecific antibody recognising factors (F) IX/IXa and
      X/Xa, can accelerate FIXa-catalysed FX activation by bridging FIXa and FX in a
      manner similar to FVIIIa. However, details of the emicizumab-antigen interactions
      have not been reported so far. In this study, we first showed by surface plasmon
      resonance analysis that emicizumab bound FIX, FIXa, FX, and FXa with moderate
      affinities (KD = 1.58, 1.52, 1.85, and 0.978 uM, respectively). We next showed by
      immunoblotting analysis that emicizumab recognised the antigens' epidermal growth
      factor (EGF)-like domains. We then performed KD-based simulation of equilibrium
      states in plasma for quantitatively predicting the ways that emicizumab would
      interact with the antigens. The simulation predicted that only a small part of
      plasma FIX, FX, and emicizumab would form antigen-bridging FIX-emicizumab-FX
      ternary complex, of which concentration would form a bell-shaped relationship
      with emicizumab concentration. The bell-shaped concentration dependency was
      reproduced by plasma thrombin generation assays, suggesting that the plasma
      concentration of the ternary complex would correlate with emicizumab's cofactor
      activity. The simulation also predicted that at 10.0-100 ug/ml of emicizumab
      levels shown in a previous study to be clinically effective-the majority of
      plasma FIX, FX, and emicizumab would exist as monomers. In conclusion, emicizumab
      binds FIX/FIXa and FX/FXa with micromolar affinities at their EGF-like domains.
      The KD-based simulation predicted that the antigen-bridging ternary complex
      formed in circulating plasma would correlate with emicizumab's cofactor activity,
      and the majority of FIX and FX would be free and available for other coagulation
      reactions.

PMID- 28451692
TI  - Application of quantitative second-harmonic generation microscopy to posterior
      cruciate ligament for crimp analysis studies.
AB  - We use second-harmonic generation (SHG) microscopy to quantitatively characterize
      collagen fiber crimping in the posterior cruciate ligament (PCL). The obtained
      SHG images are utilized to define three distinct categories of crimp organization
      in the PCL. Using our previously published spatial-frequency analysis, we develop
      a simple algorithm to quantitatively distinguish the various crimp patterns. In
      addition, SHG microscopy reveals both the three-dimensional structural variation
      in some PCL crimp patterns as well as an underlying helicity in these patterns
      that have mainly been observed using electron microscopy. Our work highlights how
      SHG microscopy could potentially be used to link the fibrous structural
      information in the PCL to its mechanical properties.

PMID- 28451691
TI  - Tool-supported Interactive Correction and Semantic Annotation of Narrative
      Clinical Reports.
AB  - OBJECTIVES: Our main objective is to design a method of, and supporting software
      for, interactive correction and semantic annotation of narrative clinical
      reports, which would allow for their easier and less erroneous processing outside
      their original context: first, by physicians unfamiliar with the original
      language (and possibly also the source specialty), and second, by tools requiring
      structured information, such as decision-support systems. Our additional goal is
      to gain insights into the process of narrative report creation, including the
      errors and ambiguities arising therein, and also into the process of report
      annotation by clinical terms. Finally, we also aim to provide a dataset of ground
      truth transformations (specific for Czech as the source language), set up by
      expert physicians, which can be reused in the future for subsequent analytical
      studies and for training automated transformation procedures. METHODS: A three
      phase preprocessing method has been developed to support secondary use of
      narrative clinical reports in electronic health record. Narrative clinical
      reports are narrative texts of healthcare documentation often stored in
      electronic health records. In the first phase a narrative clinical report is
      tokenized. In the second phase the tokenized clinical report is normalized. The
      normalized clinical report is easily readable for health professionals with the
      knowledge of the language used in the narrative clinical report. In the third
      phase the normalized clinical report is enriched with extracted structured
      information. The final result of the third phase is a semi-structured normalized
      clinical report where the extracted clinical terms are matched to codebook terms.
      Software tools for interactive correction, expansion and semantic annotation of
      narrative clinical reports has been developed and the three-phase preprocessing
      method validated in the cardiology area. RESULTS: The three-phase preprocessing
      method was validated on 49 anonymous Czech narrative clinical reports in the
      field of cardiology. Descriptive statistics from the database of accomplished
      transformations has been calculated. Two cardiologists participated in the
      annotation phase. The first cardiologist annotated 1500 clinical terms found in
      49 narrative clinical reports to codebook terms using the classification systems
      ICD 10, SNOMED CT, LOINC and LEKY. The second cardiologist validated annotations
      of the first cardiologist. The correct clinical terms and the codebook terms have
      been stored in a database. CONCLUSIONS: We extracted structured information from
      Czech narrative clinical reports by the proposed three-phase preprocessing method
      and linked it to electronic health records. The software tool, although generic,
      is tailored for Czech as the specific language of electronic health record pool
      under study. This will provide a potential etalon for porting this approach to
      dozens of other less-spoken languages. Structured information can support medical
      decision making, quality assurance tasks and further medical research.

PMID- 28451693
TI  - Impact of communicative head movements on the quality of functional near-infrared
      spectroscopy signals: negligible effects for affirmative and negative gestures
      and consistent artifacts related to raising eyebrows.
AB  - Functional near-infrared spectroscopy (fNIRS) is currently one of the most
      promising tools in the neuroscientific research to study brain hemodynamics
      during naturalistic social communication. The application of fNIRS by studies in
      this field of knowledge has been widely justified by its strong resilience to
      motion artifacts, including those that might be generated by communicative head
      and facial movements. Previous studies have focused on the identification and
      correction of these artifacts, but a quantification of the differential
      contribution of common communicative movements on the quality of fNIRS signals is
      still missing. We assessed the impact of four movements (nodding head up and
      down, reading aloud, nodding head sideways, and raising eyebrows) performed
      during rest and task conditions on two metrics of signal quality control: an
      estimative of signal-to-noise performance and the negative correlation between
      oxygenated and deoxygenated hemoglobin (oxy-Hb and deoxy-Hb). Channel-wise group
      analysis confirmed the robustness of the fNIRS technique to head nodding
      movements but showed a large effect of raising eyebrows in both signal quality
      control metrics, both during task and rest conditions. Reading aloud did not
      disrupt the expected anticorrelation between oxy-Hb and deoxy-Hb but had a
      relatively large effect on signal-to-noise performance. These findings may have
      implications to the interpretation of fNIRS studies examining communicative
      processes.

PMID- 28451694
TI  - Production pressures among anaesthesiologists in Singapore.
AB  - INTRODUCTION: Production pressure is the pressure on personnel to prioritise
      production ahead of safety. We assessed the prevalence of production pressures
      among anaesthesiologists in Singapore. METHODS: A random online survey was
      conducted among local anaesthesiologists. Questions were asked about attitudes to
      production pressures in the work environment, occurrence of situations involving
      unsafe actions, and rating of the intensity of external and internal sources of
      pressure. RESULTS: Demographically, our respondents were largely similar to all
      anaesthesiologists in Singapore and were fairly distributed across various
      tertiary hospitals. Nearly half (44.5%) had witnessed production pressures, with
      a colleague pressured to conduct anaesthesia in an unsafe manner. Such events
      included pressure from surgeons to proceed for elective surgery in patients
      without adequate optimisation, pressure to employ anaesthetic techniques that
      surgeons wanted, having to source for operating rooms to finish the surgeon's
      list, and being misled regarding surgical time. Over half (52.3%) made errors in
      clinical judgement due to excess workload. A heavy elective list workload was
      significantly associated with proceeding with patients despite lack of
      appropriate support, making changes to practices to avoid delaying the start of
      surgery and sourcing for operating rooms to finish the surgeon's list (p < 0.05),
      and being pressured to proceed with patients that the anaesthesiologist would
      otherwise have cancelled (p < 0.01). The need to avoid delaying the start of
      surgery and reduce turnover time between patients were the top-ranked internal
      and external pressures, respectively. CONCLUSION: Production pressure is
      prevalent among anaesthesiologists in Singapore and is correlated with a heavy
      workload.

PMID- 28451695
TI  - Low maternal serum pregnancy-associated plasma protein-A as a risk factor of
      preeclampsia.
AB  - INTRODUCTION: Low levels of pregnancy-associated plasma protein-A (PAPP-A) might
      be associated with abnormal placentation, leading to the development of
      preeclampsia during late gestation. We aimed to determine the association between
      low serum PAPP-A levels and rates of preeclampsia in Thai women with otherwise
      low-risk pregnancies. METHODS: A cohort study was conducted on consecutive
      singleton pregnancies undergoing first trimester screening for fetal Down
      syndrome at a tertiary centre hospital. A prospective database was assessed for
      patient records, including PAPP-A levels, pregnancy outcomes and obstetrics
      complications. Pregnancies with potential causes of preeclampsia were excluded.
      Enrolled women were categorised into two groups: women with normal PAPP-A levels
      (>= 10th percentile; control group); and those with low PAPP-A levels (< 10th
      percentile; study group). The main outcome measure was rate of preeclampsia.
      RESULTS: Of 6,887 women screened, 3,830 were available for analysis and 167 were
      excluded due to potential confounders. Of the remaining 3,663 women enrolled, 357
      women were categorised as having low PAPP-A levels and 3,306 had normal PAPP-A
      levels. The prevalence of preeclampsia (8.4% vs. 2.6%) and early-onset
      preeclampsia (i.e. before 34 weeks of gestation) (1.1% vs. 0.1%) was
      significantly higher (relative risk 3.27 and 9.26, respectively) in women from
      the study group than in the control group. CONCLUSION: Pregnancy with PAPP-A
      levels < 10th percentile was significantly associated with an increased risk of
      preeclampsia that tended toward early development. Therefore, pregnant women with
      low PAPP-A levels in the first trimester should be considered to be at increased
      risk of preeclampsia.

PMID- 28451696
TI  - Incidence, aetiology and injury characteristics of traumatic spinal cord injury
      in Stockholm, Sweden: A prospective, population-based update.
AB  - OBJECTIVES: To update the incidence rate, aetiology and injury characteristics of
      acutely-injured adults with traumatic spinal cord injury in Stockholm, Sweden,
      using international standards of reporting. STUDY DESIGN: Prospective, (regional)
      population-based observation. SUBJECTS: Forty-nine consecutively enrolled
      individuals. METHODS: A surveillance system of newly-injured adults with
      traumatic spinal cord injury was implemented for an 18-month period. The
      International Spinal Cord Injury Core Data Set was used to collect data on those
      who survived the first 7 days post-injury. RESULTS: After an 18-month period, 49
      incident cases were registered, of whom 45 were included in this study. The crude
      incidence rate was 19.0 per million, consisting mainly of men (60%), and the mean
      age of the cohort was 55 years (median 58). Causes of injury were almost
      exclusively limited to falls and transport-related events, accounting for 58% and
      40% of cases, respectively. The incidence has remained stable when compared with
      the previous study; however, significant differences exist for injury aetiology
      (p = 0.004) and impairment level (p = 0.01) in that more fall- and transport
      related spinal cord injury occurred, and a larger proportion of persons was left
      with resultant tetraplegia, in the current study, compared with more sport
      related injuries and those left with paraplegia in the previous study.
      CONCLUSION: The incidence rate appeared to remain stable in Stockholm, Sweden.
      However, significant changes in injury aetiology and impairment-level post injury
      were found, compared with the previous study. There remains a need for developing
      fall-related prevention strategies in rehabilitation settings as well as in
      population-based programmes.

PMID- 28451697
TI  - Assessment and treatment of spastic equinovarus foot after stroke: Guidance from
      the Mont-Godinne interdisciplinary group.
AB  - OBJECTIVE: To present interdisciplinary practical guidance for the assessment and
      treatment of spastic equinovarus foot after stroke. RESULTS: Clinical examination
      and diagnostic nerve block with anaesthetics determine the relative role of the
      factors leading to spastic equinovarus foot after stroke: calf spasticity,
      triceps surae - Achilles tendon complex shortening and dorsiflexor muscles
      weakness and/or imbalance. Diagnostic nerve block is a mandatory step in
      determining the cause(s) of, and the most appropriate treatment(s) for, spastic
      equinovarus foot. Based on interdisciplinary discussion, and according to a
      patient-oriented goal approach, a medical and/or surgical treatment plan is
      proposed in association with a rehabilitation programme. Spasticity is treated
      with botulinum toxin or phenol-alcohol chemodenervation and neurotomy, shortening
      is treated by stretching and muscle-tendon lengthening, and weakness is treated
      by ankle-foot orthosis, functional electrical stimulation and tendon transfer.
      These treatments are frequently combined. CONCLUSION: Based on 20 years of
      interdisciplinary expertise of management of the spastic foot, guidance was
      established to clarify a complex problem in order to help clinicians treat
      spastic equinovarus foot. This work should be the first step in a more global
      international consensus.

PMID- 28451699
TI  - ?

PMID- 28451698
TI  - [Still's disease in children and adults].
AB  - Systemic juvenile idiopathic arthritis (sJIA) is characterized by fever,
      arthritis, and other signs of systemic inflammation. Historically, sJIA was named
      Still's disease after George Frederic Still, who first reported patients.
      Individuals who manifest after the 16th birthday are diagnosed with adult onset
      Still's disease (AOSD). The pathophysiology of sJIA and AOSD are incompletely
      understood. Increased activation of inflammasomes and the expression of
      proinflammatory cytokines play a central role. S100 proteins, which can activate
      Toll-like receptors, thus, maintaining positive feedback loops, have also been
      detected at increased levels in sera from sJIA patients. Reduced expression of
      the immune-modulatory cytokine IL-10 may further contribute to immune cell
      activation and the production of proinflammatory molecules. Here, we discuss the
      clinical picture, differential diagnoses, the current pathophysiological
      understanding, and treatment options in sJIA and AOSD.

PMID- 28451700
TI  - Physical, sexual and social health factors associated with the trajectories of
      maternal depressive symptoms from pregnancy to 4 years postpartum.
AB  - PURPOSE: Few studies have examined the course of maternal depressive across
      pregnancy and early parenthood. The aim of this study was to identify the
      physical, sexual and social health factors associated with the trajectories of
      maternal depressive symptoms from pregnancy to 4 years postpartum. METHOD: Data
      were drawn from 1102 women participating in the Maternal Health Study, a
      prospective pregnancy cohort study in Melbourne, Australia. Self-administered
      questionnaires were completed at baseline (<24 weeks gestation), and at 3-, 6-,
      12-, and 18 months, and 4 years postpartum. RESULTS: Latent class analysis
      modelling identified three distinct classes representing women who experienced
      minimal depressive symptoms (58.4%), subclinical symptoms (32.7%), and
      persistently high symptoms from pregnancy to 4 years postpartum (9.0%). Risk
      factors for subclinical and persistently high depressive symptoms were having
      migrated from a non-English speaking country, not being in paid employment during
      pregnancy, history of childhood physical abuse, history of depressive symptoms,
      partner relationship problems during pregnancy, exhaustion at 3 months
      postpartum, three or more sexual health problems at 3 months postpartum, and fear
      of a partner since birth at 6 months postpartum. CONCLUSIONS: This study
      highlights the complexity of the relationships between emotional, physical,
      sexual and social health, and underscores the need for health professionals to
      ask women about their physical and sexual health, and consider the impact on
      their mental health throughout pregnancy and the early postpartum.

PMID- 28451701
TI  - The anatomical relationship of the neurovascular structures in direct posterior
      lateral gastrocnemius split approach for posterolateral tibial plateau fractures.
AB  - PURPOSE: To evaluate the distances between the incision and neurovascular
      structures in direct posterior split-gastrocnemius approach for tibial plateau
      fractures. METHODS: Thirteen fresh-frozen cadavers were used in the study. The
      distance between the neurovascular structures medial and lateral to the incision
      was measured from the tibial joint line and at a level 5 cm distal to the joint
      line. RESULTS: The mean distance between the incision and medial neurovascular
      structures was 10.09 +/- 3.47 mm (range 5.63-16.51 mm) at the level of the tibial
      joint line and 10.39 +/- 2.57 mm (range 5.79-14.09 mm) at a level 5 cm distal to
      the joint line. The mean distance between the incision and the common peroneal
      nerve was 13.44 +/- 4.17 mm (range 6.28-20.72 mm) at the level of the tibial
      joint line and 19.56 +/- 5.24 mm (range 12.58-26.74 mm) at a level 5 cm distal to
      the joint line. CONCLUSIONS: In isolated posterolateral tibial plateau fractures,
      it is possible to apply anatomical reduction and buttress plating on the
      posterior surface with a direct posterior split-gastrocnemius approach. With a
      thorough understanding of the regional anatomy, this approach can be safely
      performed by experienced orthopaedists.

PMID- 28451702
TI  - Transcatheter vs. surgical aortic valve replacement and medical treatment :
      Systematic review and meta-analysis of randomized and non-randomized trials.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as the
      procedure of choice for patients with severe aortic stenosis (AS) and high
      perioperative risk. We performed a meta-analysis to compare the mortality related
      to TAVR with medical therapy (MT) and surgical aortic valve replacement (SAVR).
      METHODS: A systematic literature search was conducted by two independent
      investigators from the database inception to 30 December 2014. Relative risk (RR)
      and odds ratio (OR) were calculated and graphically displayed in forest plots. We
      used I 2 for heterogeneity (meta-regression) and Egger's regression test of
      asymmetry (funnel plots). RESULTS: We included 24 studies (n = 19 observational
      studies; n = 5 randomized controlled trials), with a total of 7356 patients in
      this meta-analysis. Mean age had a substantial negative impact on the long-term
      survival of AS patients (OR = 1.544; 95% CI: 1.25-1.90). Compared with MT, TAVR
      showed a statistically significant benefit for all-cause mortality at 12 months
      (OR = 0.68; 95% CI: 0.49-0.95). Both TAVR and SAVR were associated with better
      outcomes compared with MT. TAVR showed lower all-cause mortality over SAVR at 12
      months (OR = 0.81; 95% CI: 0.68-0.97). The comparison between SAVR and TAVR at 2
      years revealed no significant difference (OR = 1.09; 95% CI: 1.01-1.17).
      CONCLUSION: In AS, both TAVR and SAVR provide a superior prognosis to MT and,
      therefore, MT is not the preferred treatment option for AS. Furthermore, our data
      show that TAVR is associated with lower mortality at 12 months compared with
      SAVR. Further studies are warranted to compare the long-term outcome of TAVR
      versus SAVR beyond a 2-year follow-up period.

PMID- 28451703
TI  - [Inflammatory cardiomyopathy and myocarditis].
AB  - We describe diagnosis, differential diagnosis, multimodality imaging and medical
      and invasive diagnostic treatment in patients with inflammatory cardiomyopathy
      and myocarditis under etiological considerations in reference to a landmark
      position paper of the Working Group Myocardial and Pericardial Diseases of the
      European Society of Cardiology together with recent developments in diagnosis and
      treatment. Diagnosis of the symptomatic patient is the assessment of etiology of
      inflammatory cardiomyopathy, followed by the clinical presentation, course,
      treatment option and prognosis. Viral myocarditis in its different facets can
      clearly be separated from autoreactive forms by histological and molecular
      methods in the endomyocardial biopsy, thus leading to an individualized targeted
      therapy beyond heart failure treatment.

PMID- 28451705
TI  - Demonstration of a box-stitch technique for laparoscopic uterosacral ligament
      suspension.
AB  - AIM: We demonstrate a novel box stitch technique of laparoscopic post
      hysterectomy uterosacral ligament suspension for apical prolapse in restorative
      pelvic reconstructive surgery. MATERIAL AND METHODS: We present a case of a 58yo
      female with symptomatic stage III pelvic organ prolapse with a history of a total
      abdominal hysterectomy 30 years prior. She strongly desired the usage of no
      synthetic or biologic mesh for her restorative surgical repair. This video
      provides a step-by-step guide on how to perform a laparoscopic box stitch as a
      technique for uterosacral ligament suspension as an apical native tissue option
      for patients with the need for post hysterectomy apical prolapse. CONCLUSION:
      This video demonstrates a novel box-stitch technique of laparoscopic post
      hysterectomy uterosacral ligament suspension as a native tissue option for
      minimally invasive reconstructive surgery. The procedure is a reasonable option
      to address apical prolapse in patients who do not desire or who are unable to
      have synthetic or biologic mesh placed for restorative reconstructive prolapse
      surgery.

PMID- 28451706
TI  - Registering a clinical trial.

PMID- 28451704
TI  - [Benign tumours and tumour-like lesions of the bone : General treatment
      principles].
AB  - BACKGROUND: Benign bone lesions are much more common than malignant lesions. Some
      benign bone tumors have a characteristic and typical radiographic appearance,
      while others are more challenging. Therapy of benign bone tumors differs greatly.
      While the majority of benign bone tumors do not require surgical therapy, other
      specific lesions, e. g. aneurysmal bone cysts or giant cell tumors (GCT) of the
      bone require surgery due to their locally aggressive behavior. DIAGNOSTICS: The
      major challenge for the radiologist and/or pathologist is the differentiation
      between a benign and low-grade malignant lesion (e. g. enchondroma versus low
      grade chondrosarcoma) for which all available clinical and radiographic
      information is mandatory. Therefore, surgical therapy is rather more often
      performed than necessary due to uncertainty in many cases. THERAPY: Novel
      systemic therapies are available for fibrous dysplasia and GCT of the bone:
      Fibrous dysplasia can be treated with bisphosphonates, and GCT responds to
      denosumab. In fact, denosumab has been approved for the treatment of irresectable
      GCT. Osteoid osteoma is fairly easy to recognize and also to treat given the
      characteristic clinical presentation and rapid and effective response to local
      therapy (possible as percutaneous thermo-/laser ablation). In summary, several
      therapeutic options exist for benign bone tumors, and the choice depends upon the
      tendency/risk of local recurrence, the rate of surgical complications, options
      for defect reconstruction, postoperative functional deficits, and specific
      patient characteristics.

PMID- 28451707
TI  - [Factitious disorders].
AB  - Patients with factitious disorders intentionally fabricate, exaggerate or feign
      physical and/or psychiatric symptoms for various open and covert psychological
      reasons. There are many issues regarding the diagnostic state and classification
      of factitious disorders. Both the categorical differentiation of and clinical
      continuum ranging from somatoform/dissociative disorders to malingering are being
      controversially debated. Epidemiological studies on the frequency of factitious
      disorder meet basic methodological difficulties. Reported rates of prevalence and
      incidence in the professional literature most probably have to be considered
      underestimations. Illness deception and self-harm as core features of the
      abnormal illness behaviour in factitious disorder may refer to various highly
      adverse and traumatic experiences during early development in a subgroup of
      patients. Chronic courses of illness prevail; however, there are also episodic
      variants.

PMID- 28451708
TI  - Anterior meniscopexy: a meniscal sparing technique for the treatment of locking
      but intact discoid lateral meniscus.
AB  - PURPOSE: Symptomatic discoid lateral meniscus without tears has traditionally
      been treated with excision of part or the entire meniscus. Resection of 15-34% of
      the meniscus increases tibiofemoral contact pressures by more than 350%.
      Treatment of discoid lateral meniscus with partial or total meniscectomy in
      childhood increases the risk of early-onset osteoarthritis in the knee. The
      incidence of osteoarthritis is directly proportional to the amount of meniscal
      tissue resected. This paper describes the meniscus-preserving technique of
      meniscopexy and presents the outcomes of all patients who have undergone this
      procedure in the management of lateral discoid meniscus in a single unit over a
      14-year period. METHODS: A retrospective study was carried out reviewing all
      patients who underwent meniscopexy for the treatment of MRI-confirmed discoid
      lateral meniscus without meniscal tear between 2001 and 2015 with a minimum of 1
      year follow-up. Eleven patients (12 knees) were identified using a patient
      database of all patients that had undergone this procedure in our institution.
      Two patients were excluded from the final results, so nine patients (10 knees)
      were scored post-operatively at last follow-up using the Lysholm knee score. We
      reviewed all available post-operative MRI scans and recorded any complications.
      RESULTS: Four patients were male and seven were female. The median age of the
      patients at the time of surgery was 9 (6-14), and the median follow-up was 4.5
      years (2-14). The median Lysholm knee score was 91 (86-100). The outcome for all
      patients scored was either good or excellent. CONCLUSION: The established
      treatment options for symptomatic discoid lateral meniscus without associated
      tear involve resection of meniscal tissue. Using this technique, all the meniscal
      tissue is preserved, thus reducing the risk of arthritic change in the future.
      MRI studies performed post-operatively suggested normalisation of meniscal
      morphology with time. Meniscopexy offers an effective alternative to the
      established treatment options in the management of symptomatic discoid lateral
      meniscus without meniscal tears. LEVEL OF EVIDENCE: IV.

PMID- 28451709
TI  - A dosing algorithm for metformin based on the relationships between exposure and
      renal clearance of metformin in patients with varying degrees of kidney function.
AB  - PURPOSE: The aims of this study were to investigate the relationship between
      metformin exposure, renal clearance (CLR), and apparent non-renal clearance of
      metformin (CLNR/F) in patients with varying degrees of kidney function and to
      develop dosing recommendations. METHODS: Plasma and urine samples were collected
      from three studies consisting of patients with varying degrees of kidney function
      (creatinine clearance, CLCR; range, 14-112 mL/min). A population pharmacokinetic
      model was built (NONMEM) in which the oral availability (F) was fixed to 0.55
      with an estimated inter-individual variability (IIV). Simulations were performed
      to estimate AUC0-tau, CLR, and CLNR/F. RESULTS: The data (66 patients, 327
      observations) were best described by a two-compartment model, and CLCR was a
      covariate for CLR. Mean CLR was 17 L/h (CV 22%) and mean CLNR/F was 1.6 L/h
      (69%).The median recovery of metformin in urine was 49% (range 19-75%) over a
      dosage interval. When CLR increased due to improved renal function, AUC0-tau
      decreased proportionally, while CLNR/F did not change with kidney function.
      Target doses (mg/day) of metformin can be reached using CLCR/3 * 100 to obtain
      median AUC0-12 of 18-26 mg/L/h for metformin IR and AUC0-24 of 38-51 mg/L/h for
      metformin XR, with Cmax < 5 mg/L. CONCLUSIONS: The proposed dosing algorithm can
      be used to dose metformin in patients with various degrees of kidney function to
      maintain consistent drug exposure. However, there is still marked IIV and
      therapeutic drug monitoring of metformin plasma concentrations is recommended.

PMID- 28451710
TI  - Thalamic inputs to dorsomedial striatum are involved in inhibitory control:
      evidence from the five-choice serial reaction time task in rats.
AB  - RATIONALE: Corticostriatal circuits are widely implicated in the top-down control
      of attention including inhibitory control and behavioural flexibility. However,
      recent neurophysiological evidence also suggests a role for thalamic inputs to
      striatum in behaviours related to salient, reward-paired cues. OBJECTIVES: Here,
      we used designer receptors exclusively activated by designer drugs (DREADDs) to
      investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial
      striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats.
      METHODS: The 5CSRTT requires sustained attention in order to detect spatially and
      temporally distributed visual cues and provides measures of inhibitory control
      related to impulsivity (premature responses) and compulsivity (perseverative
      responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2
      CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1
      MUl bilateral; 3 MUM) or vehicle, was injected into DMS 1 h before behavioural
      testing. Task parameters were manipulated to increase attention load or reduce
      stimulus predictability respectively. RESULTS: We found that inhibition of the Pf
      DMS projection significantly increased perseverative responses when stimulus
      predictability was reduced but had no effect on premature responses or response
      accuracy, even under increased attentional load. Control experiments showed no
      effects on locomotor activity in an open field. CONCLUSIONS: These results
      complement previous lesion work in which the DMS and orbitofrontal cortex were
      similarly implicated in perseverative responses and suggest a specific role for
      thalamostriatal inputs in inhibitory control.

PMID- 28451711
TI  - Human Hair, Baltic Grey Seal (Halichoerus grypus) Fur and Herring Gull (Larus
      argentatus) Feathers as Accumulators of Bisphenol A and Alkylphenols.
AB  - The purpose of the study was to determine the concentration of bisphenol A (BPA),
      4-tert-octylphenol (OP), and 4-nonylphenol (NP), in human hair, the fur of Baltic
      grey seals and the feathers of herring gulls. Hair was collected from 42
      volunteers, while grey seal fur (n = 17) came from the seal centre in Hel (Marine
      Station of Institute of Oceanography, University of Gdansk) and gull covert
      feathers (n = 26) were collected from dead herring gulls along the Southern
      Baltic coast. Assays of phenol derivatives were conducted using the high
      performance liquid chromatography with fluorescence detection technique. In human
      hair, the mean BPA concentration amounted to 411.2 ng g-1 dw, OP 131.2 ng g-1 dw,
      NP 4478.4 ng g-1 dw, in seal fur BPA 67.5 ng g-1 dw, OP 62.8 ng g-1 dw, NP 39.1
      ng g-1 dw, and in feathers BPA 145.1 ng g-1 dw, OP 162.0 ng g-1 dw, NP 37.7 ng g
      1 dw. The increase of the analysed EDCs in hair was significantly influenced by
      diet rich in products of marine origin, as well as hair colouring, heating up
      food in plastic containers, using home cleaning products without protective
      gloves and wearing newly purchased clothes without washing them first. The
      concentration of phenol derivatives in seal fur was influenced solely by the
      uniform diet rich in fish. In birds, the feeding area during molting
      significantly influenced the concentration of BPA, OP and NP found in covert
      feathers.

PMID- 28451712
TI  - Studies of Lipid Monolayers Prepared from Native and Model Plant Membranes in
      Their Interaction with Zearalenone and Its Mixture with Selenium Ions.
AB  - The impact of zearalenone and selenate ions on the monolayers of 1,2-dipalmitoyl
      phosphatidylcholine (DPPC), 1,2-dipalmitoyl-3-trimethylammonium-propane (DPTAP),
      and the lipid mixtures (phospholipids and galactolipids) extracted from wheat
      plasmalemma has been studied using Langmuir trough technique and Brewster angle
      microscopy (BAM). The zearalenone is a mycotoxin that exerts toxic effects on the
      cells of plants and animals. Monolayers' properties were characterized by surface
      pressure (pi)-molecular area (A) isotherms. It was found that zearalenone
      interacts with lipid monolayers causing their expansion. The selenate ions, added
      to the subphase together with zearalenone, reduce the effect of this mycotoxin on
      the surface properties of lipid films.

PMID- 28451713
TI  - Potential of Osteoblastic Cells Derived from Bone Marrow and Adipose Tissue
      Associated with a Polymer/Ceramic Composite to Repair Bone Tissue.
AB  - One of the tissue engineering strategies to promote bone regeneration is the
      association of cells and biomaterials. In this context, the aim of this study was
      to evaluate if cell source, either from bone marrow or adipose tissue, affects
      bone repair induced by osteoblastic cells associated with a membrane of
      poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT). Mesenchymal
      stem cells (MSC) were isolated from rat bone marrow and adipose tissue and
      characterized by detection of several surface markers. Also, both cell
      populations were cultured under osteogenic conditions and it was observed that
      MSC from bone marrow were more osteogenic than MSC from adipose tissue. The bone
      repair was evaluated in rat calvarial defects implanted with PVDF-TrFE/BT
      membrane and locally injected with (1) osteoblastic cells differentiated from MSC
      from bone marrow, (2) osteoblastic cells differentiated from MSC from adipose
      tissue or (3) phosphate-buffered saline. Luciferase-expressing osteoblastic cells
      derived from bone marrow and adipose tissue were detected in bone defects after
      cell injection during 25 days without difference in luciferin signal between
      cells from both sources. Corroborating the in vitro findings, osteoblastic cells
      from bone marrow combined with the PVDF-TrFE/BT membrane increased the bone
      formation, whereas osteoblastic cells from adipose tissue did not enhance the
      bone repair induced by the membrane itself. Based on these findings, it is
      possible to conclude that, by combining a membrane with cells in this rat model,
      cell source matters and that bone marrow could be a more suitable source of cells
      for therapies to engineer bone.

PMID- 28451715
TI  - [Imaging in otorhinolaryngology].

PMID- 28451714
TI  - Diabetes, bone and glucose-lowering agents: clinical outcomes.
AB  - Older adults with diabetes are at higher risk of fracture and of complications
      resulting from a fracture. Hence, fracture risk reduction is an important goal in
      diabetes management. This review is one of a pair discussing the relationship
      between diabetes, bone and glucose-lowering agents; an accompanying review is
      provided in this issue of Diabetologia by Beata Lecka-Czernik (DOI 10.1007/s00125
      017-4269-4 ). Specifically, this review discusses the challenges of accurate
      fracture risk assessment in diabetes. Standard tools for risk assessment can be
      used to predict fracture but clinicians need to be aware of the tendency for the
      bone mineral density T-score and the fracture risk assessment tool (FRAX) to
      underestimate risk in those with diabetes. Diabetes duration, complications and
      poor glycaemic control are useful clinical markers of increased fracture risk.
      Glucose-lowering agents may also affect fracture risk, independent of their
      effects on glycaemic control, as seen with the negative skeletal effects of the
      thiazolidinediones; in this review, the potential effects of glucose-lowering
      medications on fracture risk are discussed. Finally, the current understanding of
      effective fracture prevention in older adults with diabetes is reviewed.

PMID- 28451716
TI  - [Interventional radiology in the head and neck region].
AB  - In interventional neuroradiology, endovascular embolization represents an
      important and helpful tool in the treatment of multiple head and neck diseases.
      These interventional procedures may be performed with curative intent, to reduce
      the surgical risk within a multimodal treatment concept, or to improve or at
      least maintain a good quality of life within a palliative therapy concept. In
      addition to a good understanding of disease pathology, knowledge of vascular
      anatomy, including collateral vessels and dangerous extracranial-intracranial
      anastomoses, is essential for successful treatment, as is implementation of an
      established technique using appropriate material. Indications for endovascular
      embolization are i. otherwise unmanageable bleeding (caused by e. g., trauma,
      vascular malformation, or tumor), ii. reduction of perioperative bleeding by
      preoperative embolization in case of a hypervascularized tumor, iii. selective
      induction of tumor necrosis by palliative embolization to enhance local tumor
      control. Major complications such as stroke, loss of vision, and cranial nerve
      palsy are mostly due to a lack of preinterventional evaluation. Regarding
      neurological deficits, interventions within the supply region of the external
      carotid artery have a complication rate below 1%.

PMID- 28451718
TI  - Complexation-mediated electromembrane extraction of highly polar basic drugs-a
      fundamental study with catecholamines in urine as model system.
AB  - Complexation-mediated electromembrane extraction (EME) of highly polar basic
      drugs (log P < -1) was investigated for the first time with the catecholamines
      epinephrine, norepinephrine, and dopamine as model analytes. The model analytes
      were extracted as cationic species from urine samples (pH 4), through a supported
      liquid membrane (SLM) comprising 25 mM 4-(trifluoromethyl)phenylboronic acid
      (TFPBA) in bis(2-ethylhexyl) phosphite (DEHPi), and into 20 mM formic acid as
      acceptor solution. EME was performed for 15 min, and 50 V was used as extraction
      voltage across the SLM. TFPBA served as complexation reagent, and selectively
      formed boronate esters by reversible covalent binding with the model analytes at
      the sample/SLM interface. This enhanced the mass transfer of the highly polar
      model analytes across the SLM, and EME of basic drugs with log P in the range -1
      to -2 was shown for the first time. Meanwhile, most matrix components in urine
      were unable to pass the SLM. Thus, the proposed concept provided highly efficient
      sample clean-up and the system current across the SLM was kept below 50 MUA.
      Finally, the complexation-mediated EME concept was combined with ultra-high
      performance liquid chromatography coupled to tandem mass spectrometry and
      evaluated for quantification of epinephrine and dopamine. Standard addition
      calibration was applied to a pooled human urine sample. Calibration curves using
      standards between 25 and 125 MUg L-1 gave a high level of linearity with a
      correlation coefficient of 0.990 for epinephrine and 0.996 for dopamine (N = 5).
      The limit of detection, calculated as three times signal-to-noise ratio, was 5.0
      MUg L-1 for epinephrine and 1.8 MUg L-1 for dopamine. The repeatability of the
      method, expressed as coefficient of variation, was 13% (n = 5). The proposed
      method was finally applied for the analysis of spiked pooled human urine sample,
      obtaining relative recoveries of 91 and 117% for epinephrine and dopamine,
      respectively.

PMID- 28451719
TI  - Dual-mode immunoassay based on shape code and infrared absorption fingerprint
      signals of silica nanorods.
AB  - Silica nanorods were synthesized through a simple one-pot emulsion-droplet-based
      growth method, in which tetraethylorthosilicate (TEOS) was used as the silica
      source, ammonia as the catalyst, and polyvinylpyrrolidone (PVP) as the structure
      directing agent and stabilizer. By controlling hydrolysis and condensation in the
      reaction process, we regulated the aspect ratios and the infrared (IR) absorption
      fingerprint signals (the transverse optical and the longitudinal optical phonon
      modes) of the silica nanorods. Based on this, a dual-mode immunoassay was
      performed for detecting model target analyte, human IgG. The shape code of the
      silica nanorods was used for simple, rapid qualitative, and sensitive semi
      quantitative immunoassay by using a conventional optical microscope. The
      characteristic IR absorption fingerprint signals of the silica nanorods allowed
      for reliable quantitative immunoassay with good selectivity and high specificity.
      The detection limit and the linear range were found out to be 0.5 pM and 1 pM-10
      nM, respectively. We expect that such dual-mode immunoassay could be applied for
      the detection of other analytes, such as protein, nucleic acids, bacteria,
      viruses, explosives, toxins, and so on. Graphical abstract A simple dual-mode
      immunoassay was performed using the shape code and infrared absorption
      fingerprint signals of silica nanorods as detection signals.

PMID- 28451717
TI  - [PET-CT in head and neck cancer].
AB  - The importance of 18F-fluorodesoxyglucose positron-emission tomography (FDG-PET)
      for the diagnosis of malignant disease is increasing. On one hand, this is due to
      the high sensitivity of this method, on the other, because the entire body can be
      examined. FDG-PET can be particularly advantageous for the diagnosis of head and
      neck tumors, where tumor staging is an important prognostic parameter and
      essentially determines the therapeutic regimen. This article presents the
      different possibilities for combined evaluation with PET and computed tomography
      (CT) for the diagnosis of patients with head and neck cancer. Special focus is
      placed on primary staging and tumor follow-up, as well as on the role of PET-CT
      in the diagnosis of patients with cancer of unknown primary origin (CUP). The use
      of PET-CT for radiotherapy planning and new aspects of PET technology are also
      discussed.

PMID- 28451723
TI  - Comment on: "Diabetes incidence and projections from prevalence surveys in Samoa
      over 1978-2013".

PMID- 28451724
TI  - Chronic loss of inhibitor-1 diminishes cardiac RyR2 phosphorylation despite
      exaggerated CaMKII activity.
AB  - Inhibitor-1 (I-1) modulates protein phosphatase 1 (PP1) activity and thereby
      counteracts the phosphorylation by kinases. I-1 is downregulated and deactivated
      in failing hearts, but whether its role is beneficial or detrimental remains
      controversial, and opposing therapeutic strategies have been proposed.
      Overactivity of Ca2+/calmodulin-dependent protein kinase II (CaMKII) with
      hyperphosphorylation of ryanodine receptors (RyR2) at the CaMKII-site is
      recognized to be central for heart failure and arrhythmias. Using an I-1
      deficient mouse line as well as transfected cell lines, we investigated the
      effects of acute and chronic modulation of I-1 on CaMKII activity and RyR2
      phosphorylation. We demonstrate that I-1 acutely modulates CaMKII by regulating
      PP1 activity. However, while ablation of I-1 should thus limit CaMKII-activation,
      we unexpectedly found exaggerated CaMKII-activation under beta-adrenergic stress
      upon chronic loss of I-1 in knockout mice. We unraveled that this is due to
      chronic upregulation of the exchange protein activated by cAMP (EPAC) leading to
      augmented CaMKII activation, and using computational modeling validated that an
      increase in EPAC expression can indeed explain our experimental findings.
      Interestingly, at the level of RyR2, the increase in PP1 activity more than
      outweighed the increase in CaMKII activity, resulting in reduced RyR
      phosphorylation at Ser-2814. Exaggerated CaMKII activation due to
      counterregulatory mechanisms upon loss of I-1 is an important caveat with respect
      to suggested therapeutic I-1-inhibition, as CaMKII overactivity has been heavily
      implicated in several cardiac pathologies.

PMID- 28451725
TI  - Deltamethrin Induced Alteration of Biochemical Parameters in Channa punctata,
      Bloch and its Amelioration by Quercetin.
AB  - We tested the impacts of pyrethroid pesticide deltamethrin and its amelioration
      by a flavonoid, quercetin, using tissue macromolecules (protein, amino acid,
      carbohydrate and glycogen) and antioxidant enzymes (superoxide dismutase,
      catalase and peroxidase) as biomarkers, on fish, Channa punctata, gill and liver.
      Our study proved that quercetin supplement alone, in the absence of pesticide,
      might be detrimental to fish health, in terms of depletion of major tissue
      macromolecules, but, such supplement may be beneficial to fish with pesticide
      associated oxidative stress. Multivariate analyses predicted that the antioxidant
      enzymes and lipid peroxidation were closely associated biomarkers; whereas tissue
      macromolecules formed a different cluster. Hence, oxidative stress biomarkers in
      fish can be considered a valuable tool in assessment of deltamethrin stress and
      its amelioration by quercetin. The work can pave the way for further research in
      establishing quercetin as a probable curative agent.

PMID- 28451726
TI  - Toxicity of Inorganic Mercury to Native Australian Grass Grown in Three Different
      Soils.
AB  - In this study, three native Australian grasses namely Iseilema membranaceum
      (Barcoo), Dichanthium sericeum (Queensland Blue) and Sporobolus africanus
      (Tussock) were grown in three different soils spiked with different
      concentrations of inorganic mercury and the root elongation was monitored up to
      28 days following the germination. Results showed that mercury at certain
      concentrations significantly inhibited the root growth of all three tested native
      grasses grown in three soils, however, the toxicity was less in the soil with
      high organic carbon content and acidic pH. The calculated EC50 values ranged from
      10 to 224 mg/kg total Hg in soil. However, the EC10 values indicated that
      existing guideline values for mercury may be of protective to the native
      Australian vegetation. Considering their tolerance to soil mercury, these grass
      species have the potential for their use in rehabilitation of mercury
      contaminated sites.

PMID- 28451727
TI  - [Secondary hyperparathyroidism after gastric bypass].

PMID- 28451728
TI  - [Laparoscopic liver resection].
AB  - Laparoscopic liver surgery has become an established procedure in the treatment
      of liver tumors. Due to its short-term and long-term advantages, the number of
      centers with experience in laparoscopic liver surgery has greatly increased in
      the last few years. The complexity of the interventions performed has nearly
      reached the level of open surgery. This article describes the importance of
      laparoscopic hepatic surgery and discusses the evidence for the procedure. In
      addition, the indications for the most frequently resected tumors, metastases of
      colorectal cancer and hepatocellular carcinoma are explained together with
      important aspects of certain tumor localizations. In addition, the authors
      explain the technical aspects of the surgical technique and give an overview on
      new developments. To illustrate the possibilities of laparoscopic liver surgery,
      a video of a complete laparoscopically performed associating liver partition and
      portal vein ligation (ALPPS) procedure is available as supplementary material.

PMID- 28451729
TI  - [Robotic pylorus-preserving pancreaticoduodenectomy : Video article].
AB  - Pylorus-preserving pancreaticoduodenectomy is one of the most complex procedures
      in general surgery. Laparoscopic pancreaticoduodenectomy was initially described
      in 1994; however, its worldwide distribution is so far limited to only a few
      specialist centers. Robotic surgery using the DaVinci(r) system can overcome many
      limitations of laparoscopic surgery. The system is a promising tool for a more
      widespread introduction of minimally invasive surgery for pancreatic diseases.
      Mortality rates of 0-5% and pancreatic fistula rates of 0-35% are described in
      the literature; therefore, thorough complication management is crucial in the
      postoperative course. The video presents a robotic pylorus-preserving
      pancreaticoduodenectomy for periampullary carcinoma in a female patient.

PMID- 28451730
TI  - [Inguinal hernia repair in TAPP technique in a day-case surgery setting - at what
      price?]
AB  - BACKGROUND: TAPP surgery can be considered as a gold standard in inguinal hernia
      repair. Patients benefit of a faster reconvalescence and less pain compared to
      other techniques. TAPP surgery in Germany is performed in an in-patient setting
      routinely. However, according to European guidelines, inguinal hernia surgery
      should be considered as day-case surgery whenever possible. OBJECTIVES: The
      safety of day-case surgery was examined in relation to postoperative pain,
      complications, comorbidities, recurrent inguinal hernia and bilateral procedures.
      MATERIAL AND METHODS: In a retrospective, monocentric study we analyzed 522
      elective inguinal hernia repairs using TAPP technique in a specialized hernia
      center. Supplemental data from Herniamed registry is analyzed. RESULTS: Parts of
      the procedures should be performed in an in-patient setting, whereas a much
      larger number of cases should be carried out as day-case surgeries. Logistic
      regression analyses show that "age", "bilateral procedures" and "comorbidities"
      affect the complication rate. "Age" and "recurrent inguinal hernia" are risk
      factors for an increased need for analgetic medication. Furthermore, we present
      an actual distribution of day-case vs. in-patient surgeries in inguinal hernia
      repair based on data from the Herniamed registry. CONCLUSION: A much larger part
      of procedures could safely be carried out as day-case surgeries. Based on a false
      incentive there is an incorrect steering in the German health system. These
      procedures cannot be carried out covering the costs as day-surgery cases. If
      there is no reevaluation of the proceeds of these procedures in a day-case
      surgery setting, the reasonable quality in treatment is compromised especially in
      inguinal hernia surgery.

PMID- 28451731
TI  - Identification of vertebral fractures: a moderately severe solution?

PMID- 28451732
TI  - A multicenter retrospective study of the risk factors associated with medication
      related osteonecrosis of the jaw after tooth extraction in patients receiving
      oral bisphosphonate therapy: can primary wound closure and a drug holiday really
      prevent MRONJ?
AB  - : Root amputation, extraction of a single tooth, bone loss or severe tooth
      mobility, and an unclosed wound were significantly associated with increased risk
      of developing medication-related osteonecrosis of the jaw (MRONJ). We recommend a
      minimally traumatic extraction technique, removal of any bone edges, and mucosal
      wound closure as standard procedures in patients receiving bisphosphonates.
      INTRODUCTION: Osteonecrosis of the jaws can occur following tooth extraction in
      patients receiving bisphosphonate drugs. Various strategies for minimizing the
      risk of MRONJ have been advanced, but no studies have comprehensively analyzed
      the efficacy of factors such as primary wound closure, demographics, and drug
      holidays in reducing its incidence. The purpose of this study was to
      retrospectively investigate the relationships between these various risk factors
      after tooth extraction in patients receiving oral bisphosphonate therapy.
      METHODS: Risk factors for MRONJ after tooth extraction were evaluated using
      univariate and multivariate analysis. All patients were investigated with regard
      to demographics; type and duration of oral bisphosphonate use; whether they
      underwent a discontinuation of oral bisphosphonates before tooth extraction (drug
      holiday), and the duration of such discontinuation; and whether any additional
      surgical procedures (e.g., incision, removal of bone edges, root amputation) were
      performed. RESULTS: We found that root amputation (OR = 6.64), extraction of a
      single tooth (OR = 3.70), bone loss or severe tooth mobility (OR = 3.60), and an
      unclosed wound (OR = 2.51) were significantly associated with increased risk of
      developing MRONJ. CONCLUSIONS: We recommend a minimally traumatic extraction
      technique, removal of any bone edges, and mucosal wound closure as standard
      procedures in patients receiving bisphosphonates. We find no evidence supporting
      the efficacy of a pre-extraction short-term drug holiday from oral
      bisphosphonates in reducing the risk of MRONJ.

PMID- 28451734
TI  - MUC18 regulates IL-13-mediated airway inflammatory response.
AB  - OBJECTIVE: To evaluate the effects of MUC18 on IL-13-mediated airway inflammatory
      responses in human airway epithelial cells and in mice. MATERIALS: Primary normal
      human tracheobronchial epithelial (HTBE) cells, wild-type (WT) and Muc18 knockout
      (KO) mice, and mouse tracheal epithelial cells (mTECs) were utilized. TREATMENT:
      Cultured HTBE cells treated with MUC18 siRNA or MUC18 expressing lentivirus were
      incubated with IL-13 (10 ng/mL) for 24 h. Mice were intranasally instilled with
      500 ng of IL-13 for 3 days. mTECs were treated with IL-13 (10 ng/mL) for 3 days.
      METHODS: PCR was used to measure mRNA expression. Western Blot and ELISAs were
      used to quantify protein expression. Cytospins of bronchoalveolar lavage (BAL)
      cells were used to obtain leukocyte differentials. RESULTS: MUC18 siRNA reduced
      IL-13-mediated eotaxin-3 (183 +/- 44 vs. 380 +/- 59 pg/mL, p < 0.05), while MUC18
      overexpression increased IL-13-mediated eotaxin-3 (95 +/- 3 vs. 58 +/- 3 pg/mL, p
      < 0.05) in HTBE cells. IL-13-treated Muc18 KO mice had a lower percentage of
      neutrophils in BAL than WT mice (25 +/- 3 vs. 35 +/- 3%, p = 0.0565).
      CONCLUSIONS: These results implicate MUC18 as a potential enhancer of airway
      inflammation in a type 2 cytokine (e.g., IL-13) milieu.

PMID- 28451733
TI  - Identification and management of patients at increased risk of osteoporotic
      fracture: outcomes of an ESCEO expert consensus meeting.
AB  - : Osteoporosis represents a significant and increasing healthcare burden in
      Europe, but most patients at increased risk of fracture do not receive
      medication, resulting in a large treatment gap. Identification of patients who
      are at particularly high risk will help clinicians target appropriate treatment
      more precisely and cost-effectively, and should be the focus of future research.
      INTRODUCTION: The purpose of the study was to review data on the identification
      and treatment of patients with osteoporosis at increased risk of fracture.
      METHODS: A working group convened by the European Society for Clinical and
      Economic Aspects of Osteoporosis and Osteoarthritis met to review current data on
      the epidemiology and burden of osteoporosis and the patterns of medical
      management throughout Europe. RESULTS: In Europe in 2010, the cost of managing
      osteoporosis was estimated at ?37 billion and notably the costs of treatment and
      long-term care of patients with fractures were considerably higher than the costs
      for pharmacological prevention. Despite the availability of effective treatments,
      the uptake of osteoporosis therapy is low and declining, in particular for
      secondary fracture prevention where the risk of a subsequent fracture following a
      first fracture is high. Consequently, there is a significant treatment gap
      between those who would benefit from treatment and those who receive it, which
      urgently needs to be addressed so that the burden of disease can be reduced.
      CONCLUSIONS: Implementation of global fracture prevention strategies is a
      critical need. Future research should focus on identifying specific risk factors
      for imminent fractures, periods of high fracture risk, patients who are at
      increased risk of fracture and therapies that are most suited to such high-risk
      patients and optimal implementation strategies in primary, secondary and tertiary
      care.

PMID- 28451736
TI  - Programming of left hand exploits task set but that of right hand depends on
      recent history.
AB  - There are many differences between the left hand and the right hand. But it is
      not clear if there is a difference in programming between left hand and right
      hand when the hands perform the same movement. In current study, we carried out
      two experiments to investigate whether the programming of two hands was
      equivalent or they exploited different strategies. In the first experiment,
      participants were required to use one hand to grasp an object with visual
      feedback or to point to the center of one object without visual feedback on
      alternate trials, or to grasp an object without visual feedback and to point the
      center of one object with visual feedback on alternating trials. They then
      performed the tasks with the other hand. The result was that previous pointing
      task affected current grasping when it was performed by the left hand, but not
      the right hand. In experiment 2, we studied if the programming of the left (or
      right) hand would be affected by the pointing task performed on the previous
      trial not only by the same hand, but also by the right (or left) hand.
      Participants pointed and grasped the objects alternately with two hands. The
      result was similar with Experiment 1, i.e., left-hand grasping was affected by
      right-hand pointing, whereas right-hand grasping was immune from the interference
      from left hand. Taken together, the results suggest that when open- and closed
      loop trials are interleaved, motor programming of grasping with the right hand
      was affected by the nature of the online feedback on the previous trial only if
      it was a grasping trial, suggesting that the trial-to-trial transfer depends on
      sensorimotor memory and not on task set. In contrast, motor programming of
      grasping with the left hand can use information about the nature of the online
      feedback on the previous trial to specify the parameters of the movement, even
      when the type of movement that occurred was quite different (i.e., pointing) and
      was performed with the right hand. This suggests that trial-to-trial transfer
      with the left hand depends on some sort of carry-over of task set for dealing
      with the availability of visual feedback.

PMID- 28451737
TI  - Effects of malocclusions on facial attractiveness and their correlations with the
      divine proportion.
AB  - PURPOSE: The aim of this study was to evaluate the effects of malocclusions on
      facial attractiveness and to determine if it was correlated with the divine
      proportion. METHODS: Standard frontal facial photos were taken from 335 subjects
      in natural head position. Facial attractiveness of the subjects was evaluated by
      10 dental students using a 10-point visual analog scale (VAS). All of the
      evaluations were arranged in order, and 30 attractive subjects with the highest
      score and 30 nonattractive subjects having the lowest score were chosen. On the
      frontal photos of these subjects, 13 landmarks were determined and 12 ratios were
      measured. Two way ANOVA was used to determine the effects of malocclusions on
      facial attractiveness, Student's t test was used to compare the facial
      proportions of the attractive and nonattractive subjects, and one sample t test
      was used to define the relationships between the divine proportion and facial
      ratios. RESULTS: No statistically significant difference was found between
      malocclusion groups in terms of facial attractiveness. Of the 12 facial ratios,
      significant differences were found between attractive and nonattractive subjects
      regarding trichion-menton/nasion-menton, subnasale-menton/stomion-menton, nasion
      subnasale/stomion-menton, nasion-subnasale/nasal width, and trichion-menton/right
      left frontotemporale ratios. All of the ratios except nasion-subnasale/stomion
      menton in the attractive group and subnasale-menton/stomion-menton and nasion
      menton/nasion-trichion in the nonattractive group were found to be different from
      the divine proportion. CONCLUSIONS: Sagittal skeletal malocclusions evaluated by
      ANB angle are not effective on facial attractiveness. Facial ratios used in this
      study have little effect on attractiveness, and are different from the divine
      proportion.

PMID- 28451738
TI  - Erratum to: Dioscin-induced autophagy mitigates cell apoptosis through modulation
      of PI3K/Akt and ERK and JNK signaling pathways in human lung cancer cell lines.

PMID- 28451740
TI  - Precision toxicology based on single cell sequencing: an evolving trend in
      toxicological evaluations and mechanism exploration.
AB  - In this review, we introduce a new concept, precision toxicology: the mode of
      action of chemical- or drug-induced toxicity can be sensitively and specifically
      investigated by isolating a small group of cells or even a single cell with
      typical phenotype of interest followed by a single cell sequencing-based
      analysis. Precision toxicology can contribute to the better detection of subtle
      intracellular changes in response to exogenous substrates, and thus help
      researchers find solutions to control or relieve the toxicological effects that
      are serious threats to human health. We give examples for single cell isolation
      and recommend laser capture microdissection for in vivo studies and flow
      cytometric sorting for in vitro studies. In addition, we introduce the procedures
      for single cell sequencing and describe the expected application of these
      techniques to toxicological evaluations and mechanism exploration, which we
      believe will become a trend in toxicology.

PMID- 28451739
TI  - Understanding renal nuclear protein accumulation: an in vitro approach to explain
      an in vivo phenomenon.
AB  - Proper subcellular trafficking is essential to prevent protein mislocalization
      and aggregation. Transport of the peroxisomal enzyme D-amino acid oxidase (DAAO)
      appears dysregulated by specific pharmaceuticals, e.g., the anti-overactive
      bladder drug propiverine or a norepinephrine/serotonin reuptake inhibitor (NSRI),
      resulting in massive cytosolic and nuclear accumulations in rat kidney. To assess
      the underlying molecular mechanism of the latter, we aimed to characterize the
      nature of peroxisomal and cyto-nuclear shuttling of human and rat DAAO
      overexpressed in three cell lines using confocal microscopy. Indeed, interference
      with peroxisomal transport via deletion of the PTS1 signal or PEX5 knockdown
      resulted in induced nuclear DAAO localization. Having demonstrated the absence of
      active nuclear import and employing variably sized mCherry- and/or EYFP-fusion
      proteins of DAAO and catalase, we showed that peroxisomal proteins <=134 kDa can
      passively diffuse into mammalian cell nuclei-thereby contradicting the often
      cited 40 kDa diffusion limit. Moreover, their inherent nuclear presence and
      nuclear accumulation subsequent to proteasome inhibition or abrogated peroxisomal
      transport suggests that nuclear localization is a characteristic in the lifecycle
      of peroxisomal proteins. Based on this molecular trafficking analysis, we suggest
      that pharmaceuticals like propiverine or an NSRI may interfere with peroxisomal
      protein targeting and import, consequently resulting in massive nuclear protein
      accumulation in vivo.

PMID- 28451741
TI  - The RAG transposon is active through the deuterostome evolution and domesticated
      in jawed vertebrates.
AB  - RAG1 and RAG2 are essential subunits of the V(D)J recombinase required for the
      generation of the variability of antibodies and T cell receptors in jawed
      vertebrates. It was demonstrated that the amphioxus homologue of RAG1-RAG2 is
      encoded in an active transposon, belonging to the transposase DDE superfamily.
      The data provided support the possibility that the RAG transposon has been active
      through the deuterostome evolution and is still active in several lineages. The
      RAG transposon corresponds to several families present in deuterostomes. RAG1
      RAG2 V(D)J recombinase evolved from one of them, partially due to the new ability
      of the transposon to interact with the cellular reparation machinery. Considering
      the fact that the RAG transposon survived millions of years in many different
      lineages, in multiple copies, and that DDE transposases evolved their association
      with proteins involved in repair mechanisms, we propose that the apparition of
      V(D)J recombination machinery could be a predictable genetic event.

PMID- 28451742
TI  - Contributions of Composition and Interactions to Bacterial Respiration Are
      Reliant on the Phylogenetic Similarity of the Measured Community.
AB  - Bacterial diversity underpins many ecosystem functions; however, the impact of
      within-species variation on the relationship between diversity and function
      remains unclear. Processes involving strain differentiation, such as niche
      radiation, are often overlooked in studies that focus on phylogenetic variation.
      This study used bacterial isolates assembled in two comparable microcosm
      experiments to test how species variation affected ecosystem function. We
      compared the relationship between diversity and activity (CO2 production) in
      increasingly diverse multispecies microcosms and with multiple ecotypes of a
      single species. The bacteria used were isolated from a low-diversity environment
      and are species of potential clinical significance such as Pseudomonas
      aeruginosa. All isolates were profiled for single carbon source utilisation.
      These data showed an increased breadth of resource use in the multiple ecotypes
      when compared to the mixed-species. The study observed significantly increasing
      respiration in more complex mixed-species assemblages, which was not observed
      when ecotypes of a single species were combined. We further demonstrate that the
      variation observed in the bacterial activity was due to the roles of each of the
      constituent isolates; between different species, the interactions between the
      isolates drove the variation in activity, whilst in single species, assemblage
      variation was due to which isolates were present. We conclude that both between-
      and within-species variations play different roles in community function,
      although through different mechanisms, and should be included in models of
      changing diversity and ecosystem functioning.

PMID- 28451745
TI  - [Urinary tract infections - (not) a problem?]

PMID- 28451743
TI  - Environmental Metabarcoding Reveals Contrasting Belowground and Aboveground
      Fungal Communities from Poplar at a Hg Phytomanagement Site.
AB  - Characterization of microbial communities in stressful conditions at a field
      level is rather scarce, especially when considering fungal communities from
      aboveground habitats. We aimed at characterizing fungal communities from
      different poplar habitats at a Hg-contaminated phytomanagement site by using
      Illumina-based sequencing, network analysis approach, and direct isolation of Hg
      resistant fungal strains. The highest diversity estimated by the Shannon index
      was found for soil communities, which was negatively affected by soil Hg
      concentration. Among the significant correlations between soil operational
      taxonomic units (OTUs) in the co-occurrence network, 80% were negatively
      correlated revealing dominance of a pattern of mutual exclusion. The fungal
      communities associated with Populus roots mostly consisted of OTUs from the
      symbiotic guild, such as members of the Thelephoraceae, thus explaining the
      lowest diversity found for root communities. Additionally, root communities
      showed the highest network connectivity index, while rarely detected OTUs from
      the Glomeromycetes may have a central role in the root network. Unexpectedly high
      richness and diversity were found for aboveground habitats, compared to the root
      habitat. The aboveground habitats were dominated by yeasts from the Lalaria,
      Davidiella, and Bensingtonia genera, not detected in belowground habitats. Leaf
      and stem habitats were characterized by few dominant OTUs such as those from the
      Dothideomycete class producing mutual exclusion with other OTUs. Aureobasidium
      pullulans, one of the dominating OTUs, was further isolated from the leaf
      habitat, in addition to Nakazawaea populi species, which were found to be Hg
      resistant. Altogether, these findings will provide an improved point of reference
      for microbial research on inoculation-based programs of tailings dumps.

PMID- 28451746
TI  - [Renal cell carcinoma in older and geriatric patients].
AB  - BACKGROUND: Renal cell carcinoma (RCC) is a disease of older humans. Due to
      increased detection of tumours by ultrasound and computed tomography, the number
      of incidentally diagnosed RCCs has increased. These tumours are usually smaller
      and of lower stage. Furthermore, there is an increase of older people in the
      population. OBJECTIVES: Characteristics of tumour biology, prognosis, diagnostics
      and therapy of localized, advanced and metastatic RCC in old and geriatric
      patients are provided. METHODS: Systematic literature review, analysis and
      discussion of original research articles and expert opinions. RESULTS: The
      surgical treatment of RCC in old and geriatric patients requires attention to
      increased morbidity and mortality. Active surveillance or ablations are
      alternatives to surgical treatment in localized RCC. Systemic therapy in
      metastatic tumours exhibit analogous efficacy with slightly worse toxicity.
      CONCLUSIONS: RCC in old and geriatric patients requires an adaptation of classic
      therapeutic strategies. Management should be adjusted individually to age and
      comorbidities. Efficacy, risk and toxicity of all therapeutic options should be
      considered. A multidisciplinary approach is important for diagnosis, assessment
      and therapy. Recommendations should be discussed with patients and their
      relatives according to the individual needs, and treatment decisions should be
      based on patient preferences wherever possible.

PMID- 28451747
TI  - [Community acquired urinary tract infections - association with risk factors :
      Changes in causative organisms and resistance over time].
AB  - BACKGROUND: Published studies on community-acquired urinary tract infections
      (UTI) often do not link microbiological findings with clinical risk factors and
      patient data. MATERIALS AND METHODS: We retrospectively correlated clinical
      findings of all patients with UTI of a urological outpatient clinic with the
      respective microbiological analysis of their urine samples over 2 periods of
      time: (A: 2005-2006 and B: 2011-2012). Patients were stratified to the following
      risk groups: uncomplicated cystitis, diabetes mellitus type 2, nursing home
      resident, prostatitis/epidydimitis, permanent catheter. RESULTS: The incidence of
      Escherichia coli (p < 0.001) and proteus (p < 0.001) significantly decreased from
      period A to B, while enterococci (p = 0.003) and staphylococci (p < 0.001)
      significantly increased. Antibiotic sensitivity to fosfomycin (p < 0.001),
      doxycycline (p < 0.001), nitrofurantoin (p < 0.001), and nitroxoline increased (p
      < 0. 001) and sensitivity to amoxicillin (p < 0.001) and gentamicin decreased (p
      < 0.001). Patients with a permanent catheter had significantly poorer sensitivity
      rates (50% and less) for almost all antibiotics tested compared to the overall
      group. The risk of a UTI with 3MRGN or MRSA bacteria was significantly higher for
      catheter carriers and nursing home residents. CONCLUSIONS: Empiric antibiotic
      first-line therapy with nitrofurantoin and fosfomycin for uncomplicated community
      acquired UTIs are well indicated in conformity with guidelines. The accumulation
      of multiresistant pathogens in patients with a permanent bladder catheter
      requires restrictive use of any permanent catheter drainage.

PMID- 28451748
TI  - Effects of 4 weeks of low-load unilateral resistance training, with and without
      blood flow restriction, on strength, thickness, V wave, and H reflex of the
      soleus muscle in men.
AB  - PURPOSE: To test the effects of 4 weeks of unilateral low-load resistance
      training (LLRT), with and without blood flow restriction (BFR), on maximal
      voluntary contraction (MVC), muscle thickness, volitional wave (V wave), and
      Hoffmann reflex (H reflex) of the soleus muscle. METHODS: Twenty-two males were
      randomly distributed into three groups: a control group (CTR; n = 8); a low-load
      blood flow restriction resistance training group (BFR-LLRT; n = 7), who were an
      inflatable cuff to occlude blood flow; and a low-load resistance training group
      without blood flow restriction (LLRT; n = 7). The training consisted of four sets
      of unilateral isometric LLRT (25% of MVC) three times a week over 4 weeks.
      RESULTS: MVC increased 33% (P < 0.001) and 22% (P < 0.01) in the trained leg of
      both BFR-LLRT and LLRT groups, respectively. The soleus thickness increased 9.5%
      (P < 0.001) and 6.5% (P < 0.01) in the trained leg of both BFR-LLRT and LLRT
      groups, respectively. However, neither MVC nor thickness changed in either of the
      legs tested in the CTR group (MVC -1 and -5%, and muscle thickness 1.9 and 1.2%,
      for the control and trained leg, respectively). Moreover, V wave and H reflex did
      not change significantly in all the groups studied (Vwave/M wave ratio -7.9 and 
      2.6%, and H max/M max ratio -3.8 and -4%, for the control and trained leg,
      respectively). CONCLUSIONS: Collectively, the present data suggest that in spite
      of the changes occurring in soleus strength and thickness, 4 weeks of low-load
      resistance training, with or without BFR, does not cause any change in neural
      drive or motoneuronal excitability.

PMID- 28451749
TI  - Functional characterization of the pinoresinol-lariciresinol reductase-2 gene
      reveals its roles in yatein biosynthesis and flax defense response.
AB  - MAIN CONCLUSION: This study provides new insights into the biosynthesis
      regulation and in planta function of the lignan yatein in flax leaves.
      Pinoresinol-lariciresinol reductases (PLR) catalyze the conversion of pinoresinol
      into secoisolariciresinol (SECO) in lignan biosynthesis. Several lignans are
      accumulated in high concentrations, such as SECO accumulated as
      secoisolariciresinol diglucoside (SDG) in seeds and yatein in aerial parts, in
      the flax plant (Linum usitatissimum L.) from which two PLR enzymes of opposite
      enantioselectivity have been isolated. While LuPLR1 catalyzes the biosynthesis of
      (+)-SECO leading to (+)-SDG in seeds, the role(s) of the second PLR (LuPLR2) is
      not completely elucidated. This study provides new insights into the in planta
      regulation and function of the lignan yatein in flax leaves: its biosynthesis
      relies on a different PLR with opposite stereospecificity but also on a distinct
      expression regulation. RNAi technology provided evidence for the in vivo
      involvement of the LuPLR2 gene in the biosynthesis of (-)-yatein accumulated in
      flax leaves. LuPLR2 expression in different tissues and in response to stress was
      studied by RT-qPCR and promoter-reporter transgenesis showing that the spatio
      temporal expression of the LuPLR2 gene in leaves perfectly matches the (-)-yatein
      accumulation and that LuPLR2 expression and yatein production are increased by
      methyl jasmonate and wounding. A promoter deletion approach yielded putative
      regulatory elements. This expression pattern in relation to a possible role for
      this lignan in flax defense is discussed.

PMID- 28451750
TI  - Fe-deficiency-induced expression of bHLH104 enhances Fe-deficiency tolerance of
      Arabidopsis thaliana.
AB  - MAIN CONCLUSION: Expression of bHLH104 - GFP driven by the MYB72 promoter
      improves plants' tolerance to Fe deficiency and increases seed Fe concentrations.
      Iron (Fe) deficiency causes reduced crop yield and quality. In humans, Fe
      deficiency is directly associated with Fe-deficiency anemia. Therefore, breeding
      Fe-deficiency tolerant and Fe-enriched plants are an ideal approach to deal with
      these problems. Here, different strategies were explored to generate Fe
      deficiency tolerant and Fe-enriched plants. Unexpectedly, the overexpression of
      Fe-deficiency responsive genes (IRT1, MYB72, and bHLH100) resulted in enhanced
      sensitivity to Fe deficiency, including leaf chlorosis and short roots under Fe
      deficiency conditions. Next, three different types of Fe-deficiency responsive
      promoters (Pro IRT1 , Pro MYB72, and Pro bHLH100 ) were used to drive the
      expression of bHLH104-GFP fusion gene in Arabidopsis. Pro IRT1 :bHLH104-GFP
      plants showed the enhanced sensitivity to Fe deficiency on Fe-deficient media and
      the reduced fertility in alkaline soil. In contrast, Pro bHLH100 :bHLH104-GFP
      plants displayed a slight tolerance to Fe deficiency and Pro MYB72 :bHLH104-GFP
      plants had a significant advantage in growth in alkaline soil, including
      increased root length, chlorophyll, and biomass. Further analysis revealed that
      the expression of Fe-deficiency responsive genes was dramatically upregulated in
      both Pro MYB72 :bHLH104-GFP and Pro bHLH100 :bHLH104-GFP plants under Fe
      deficiency conditions. When grown in alkaline soil, Pro MYB72 :bHLH104-GFP plants
      greatly improved the seed yield and Fe concentration. These results are
      fundamental for plant manipulation approaches to modify tolerance to Fe
      deficiency and Fe accumulation through alterations of bHLH104 gene expression.

PMID- 28451751
TI  - Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2)
      pathway by particulate guanylyl cyclases in GH3 somatolactotropes.
AB  - The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP,
      BNP, CNP), are regulators of many endocrine tissues and exert their effects
      predominantly through the activation of their specific guanylyl cyclase receptors
      (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been
      reported in response to natriuretic peptides, this is mediated via either the
      clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack
      intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent
      cGMP-independent signalling in pituitary GH3 cells. Stimulation of GH3 cells with
      CNP resulted in a rapid and sustained enhancement of ERK1/2 phosphorylation (P
      ERK1/2), an effect that was not mimicked by dibutryl-cGMP. Furthermore, CNP
      stimulated P-ERK1/2 occurred at concentrations below that required for cGMP
      accumulation. The effect of CNP on P-ERK1/2 was sensitive to pharmacological
      blockade of MEK (U0126) and Src kinases (PP2). Silencing of the GC-B1 and GC-B2
      splice variants of the GC-B receptor by using targeted short interfering RNAs
      completely blocked the CNP effects on P-ERK1/2. CNP failed to alter GH3 cell
      proliferation or cell cycle distribution but caused a concentration-dependent
      increase in the activity of the human glycoprotein alpha-subunit promoter
      (alphaGSU) in a MEK-dependent manner. Finally, CNP also activated the p38 and JNK
      MAPK pathways in GH3 cells. These findings reveal an additional mechanism of GC-B
      signalling and suggest additional biological roles for CNP in its target tissues.

PMID- 28451752
TI  - Patient sexual function and hip replacement surgery: A survey of surgeon
      attitudes.
AB  - PURPOSE: To explore practises of orthopaedic surgeons (and residents) in
      addressing sexual function (SF) in patients before and after total hip
      arthroplasty (THA). METHODS: A 26-item questionnaire was sent to health
      professionals (n = 849); 526 (62.0%) responses were included in the analyses.
      RESULTS: About 78% of the respondents (77.5%) almost never addressed SF. The most
      mentioned reason was that "patients do not ask" (47.4%) followed by "I am not
      aware of possible needs" (38.6%). SF was even less discussed (25.9%) in elderly
      patients (>60 years). The beneficial effect of THA on SF was rated the highest in
      retired surgeons (p <= 0.001), in which male surgeons scored higher than female
      surgeons (p = 0.002). The importance of sexual dificulties (SD) in the decision
      to undergo surgery was rated lowest by residents (p = 0.020). Rating the risk for
      dislocation varied between occupations (p = 0.008) and gender (p = 0.016), female
      surgeons rated highest (median 5); 54.1% indicated the orthopaedic surgeon is
      responsible for providing information about the safe resumption of sexual
      activity. CONCLUSIONS: Surgeons show little attention to SF related issues in THA
      patients, which seems not in accordance to patients' needs. Addressing SF
      increases throughout a surgeon's career. There were divergent views and there is
      no "common advice" about the safe resumption of sexual activity. The results
      emphasize the need for guidelines and training in order to encourage addressing
      SF both, before and after THA.

PMID- 28451753
TI  - Histologic subtype needs to be considered after partial nephrectomy in patients
      with pathologic T1a renal cell carcinoma: papillary vs. clear cell renal cell
      carcinoma.
AB  - PURPOSE: We compared the oncological outcomes of papillary renal cell carcinoma
      (pRCC) with clear cell renal cell carcinoma (ccRCC) after partial nephrectomy
      (PN) in patients with pathologic T1a RCC. METHODS: After excluding patients with
      synchronous multiple renal tumors, familial RCC, and pathologic stage T1b or
      above, 759 patients with ccRCC and 84 patients with pRCC were included. We
      assessed the impact of histologic subtypes on oncologic outcomes after PN in
      patients with pathologic T1a RCC (median follow-up duration, 67 months). RESULTS:
      There was no difference in patient and tumor characteristics between the 2
      groups, except Fuhrman grade (p = 0.006). Kaplan-Meier analysis identified 5-year
      recurrence-free survival of 98.7 and 95.6% in patients with ccRCC and pRCC,
      respectively. However, 10-year recurrence-free survival in patients with ccRCC
      and pRCC was 96.1 and 73.0%, respectively (p < 0.001). Recurrence >=5 years post
      surgery was more common in patients with pRCC compared with those with ccRCC (0.3
      vs. 4.8%; p < 0.001). In multivariate analysis, pRCC [hazard ratio (HR) 5.309; p
      = 0.001] was a significant risk factor for recurrence after PN in patients with
      pathologic T1a RCC, in addition to larger tumor size (HR 1.861; p = 0.038) and
      Fuhrman grade >=3 (HR 5.176; p = 0.003). CONCLUSIONS: In patients with pathologic
      T1a RCC, recurrence after PN occurred more commonly in pRCC compared with ccRCC.
      As over half of the recurrence cases in patients with pRCC occurred >=5 years
      post surgery, a longer follow-up time is required, even for those with pathologic
      stage T1a disease.

PMID- 28451754
TI  - In reference to 'Drug-induced sleep endoscopy: the VOTE classification'.

PMID- 28451755
TI  - The interpretation of compact polysomnography/polygraphy in sleep breathing
      disorders patients: a validation's study.
AB  - : The Otorhinolaryngologist (ENT) frequently has to deal with OSA or suspicious
      OSA patients and undergone polysomnography (PSG) or portable monitoring (PM) and
      should be confident about the quality and consistency of the polysomnographic
      diagnosis. The main polysomnographic traces compressed in a unique epoch, defined
      as compact PSG/PM (CP), could represent an efficient tool to confirm the quality
      of PSG/PM Sleep Breathing Disorders diagnosis. This is a validation's study of a
      CP interpretation's method, analyzing the learning curve, the level of diagnostic
      accuracy, and the inter-operator agreement in interpreting the CP pattern between
      a group of ENT specialists not skilled in PSG/PM scoring, but managing SBD
      patients during daily practice. Seven ENT specialists have been enrolled in the
      study. 50 CP traces (ranging from normal to all main SBD patterns) have been
      showed to each participant for the interpretation and scoring process, before and
      after a 2-h theoretical-practical interactive lesson, focusing on the recognition
      of the four main oximetric patterns on CP traces (normal, phasic, prolonged, and
      overlap patterns). RESULTS: before and after the theoretical-practical
      interactive lesson, the whole diagnostic accuracy in interpreting the 50 CP has
      been reported improved from 0.12 to 0.80 (median 0.52) to 0.82-0.96 (median 0.92)
      (p = 0.006) and the inter-scorers' agreement showed a kappa value increased from
      of 0.18 to 0.75 (p < 0.0001). A complete clinical diagnostic evaluation is
      essential in OSA patients and the ENT specialist should be concerned to verify if
      the patient, suitable for surgical therapy, is affected really by an isolated
      form of OSA. The CP interpretation allows a checking of the proper nosographic
      SBD framework and could be significantly important for all ENT specialists not
      skilled in PSG/PM scoring, but managing SBD patients during daily practice. The
      data reported in our validation's study showed that the CP interpretation's
      method is easy to apply, with a rapid learning curve. The level of diagnostic
      accuracy is high with a high inter-scorer agreement in interpreting the CP
      patterns.

PMID- 28451757
TI  - Analysis of autofluorescence pattern in birdshot chorioretinopathy.
AB  - PURPOSE: To characterize and correlate the different patterns of fundus
      autofluorescence (FAF) in patients with birdshot chorioretinopathy (BSCR), with
      functional and anatomical parameters. METHODS: Twenty-one BSCR patients were
      prospectively studied in 2013 and 2014. Each patient underwent visual acuity (VA)
      and visual field (SITA standard 30.2) testing as well as fluorescein and
      indocyanine green angiography, spectral-domain optical coherence tomography (SD
      OCT) B scan, enhanced depth imaging (EDI), and fundus autofluorescence (FAF)
      imaging. The disease was classified as active, chronic, or quiescent. RESULTS:
      The patients' mean age was 60.3 +/- 9.2 years and 60% were female. Disease
      duration was 5.7 +/- 3.7 years. Autofluorescence imaging showed punctiform hyper
      FAF spots in 23 out of the 29 eyes (79%), which was significantly associated with
      a greater visual field mean deviation (-7 +/- 7 versus -3 +/- 2 dB, p = 0.04).
      Hypo-FAF was defined as peripapillary (n = 25; 86.2%), macular (n = 10; 34.5%),
      lichenoid (n = 17; 58.6%), and/or diffuse (n = 13; 44.8%). Lichenoid hypo-FAF was
      significantly associated with worse VA (0.18 +/- 0.24 vs. 0.05 +/- 0.07 LogMAR, p
      = 0.04). Macular hypo-FAF was associated with a history of macular edema (62.5%;
      p = 0.06). Diffuse hypo-FAF was observed more frequently (p = 0.01) in chronic
      disease (66.7%) than in active (0%) or quiescent disease (27.3%). CONCLUSIONS:
      Autofluorescence analysis in BRSC patients contributes to evaluating disease
      activity and could be useful to guide follow-up and treatment.

PMID- 28451758
TI  - The evaluation of diagnostic efficiency for stromal herpes simplex keratitis by
      the combination of tear HSV-sIgA and HSV-DNA.
AB  - PURPOSE: To assess the differential diagnostic values for stromal herpes simplex
      keratitis (HSK) by using tear HSV-sIgA, tear HSV-DNA, and the combination.
      METHODS: Tear samples for both eyes and the paired serum were collected from 187
      stromal HSK and 56 controls. Enzyme-linked immune sorbent assay (ELISA) was used
      to analyze the tear HSV-sIgA and serum IgG/IgM/IgA. The levels of tear HSV-DNA
      were measured by polymerase chain reaction (PCR). RESULTS: The positive rates for
      tear HSV-sIgA and HSV-DNA were 36.90% and 10.96% respectively in stromal HSK
      patients. Twelve showed positivity for both sIgA and DNA, while 46 cases were
      positive for sIgA or DNA. The sensitivity, specificity, PPV, and NPV for
      simultaneous measurement were 39.73%, 98.21%, 98.31%, and 38.46%. The total
      negative conversion rate of sIgA was 95.71%. CONCLUSIONS: The diagnostic
      efficiency of HSV-sIgA only is nearly equal to the combination of HSV-sIgA and
      HSV-DNA, and the positive result is optimum to achieve a reliable diagnosis of
      stromal HSK even in atypical or unsuspected cases.

PMID- 28451756
TI  - Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed beta-catenin
      expression, and dual intra-tumor Ki-67 labeling index compartmentalization
      challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm
      shift.
AB  - We herein report an uncommon association of intimately admixed atypical carcinoid
      (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus,
      occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by
      maximal thymectomy. The younger patient presented with a synchronous lesion and
      died of disease after 9 months, while the other patient was associated with a
      recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive
      with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case.
      Immunohistochemically, disarrayed cytoplasmic and nuclear beta-catenin expression
      was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from
      2 to 80% in the younger patient's tumor and from 3 to 45% in the other. Both
      exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was
      overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed
      CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation
      alone in the metachronous tumor (the latter with the same mutation as the first
      tumor of 17 years prior). None of the 23 T-NET controls exhibited this
      hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC
      components developed from pre-existing CTNNB1-mutated AC upon loss-of-function
      TP53 and gain-of-function JAK3 mutations in one case and an epithelial
      mesenchymal transition upon vimentin overexpression in the other case. Both
      tumors maintained intact cyclin D1-retinoblastoma machinery. Our report
      challenges the concept of secondary LCNEC as an entity that develops from pre
      existing AC as a result of tumor progression, suggesting a paradigm shift to the
      current pathogenesis of NET.

PMID- 28451759
TI  - The relationship between selected socioeconomic factors and thinness among Polish
      school-aged children and adolescents.
AB  - : The analysis was performed on a database including 17,427 records of subjects
      aged 7-18 years, randomly sampled from a population of Polish students. Thinness
      was determined using international cut-off points, defined to pass through body
      mass index of 18.5 kg/m2 at the age of 18. The weighted prevalence of thinness
      and odds ratios with 95% confidence interval were estimated for gender, birth
      weight, level of schooling and school location, gross domestic product (GDP) per
      inhabitant, family income and maternal education. Body height was analysed
      according to body mass and birth weight categories. The prevalence of thinness
      was higher among children with low birth weight and among girls. The prevalence
      of thinness decreased with increasing GDP per inhabitant. In analysis by level of
      schooling: primary-middle-secondary, prevalence of thinness decreased among boys
      and increased among girls. Thin students were significantly shorter than other
      students, and thin girls less likely participated in physical education.
      CONCLUSION: Gender and socioeconomic factors are important determinants of
      thinness among Polish children and adolescents. Public health strategies should
      address family eating practices to prevent negative effects of weight deficit,
      especially among girls/children from low GDP regions. What is Known: *
      Socioeconomic factors and gender influence weight status of children and
      adolescents. What is New: * The first time the prevalence and determinants of
      thinness based on data from a nationally representative, weighted sample of
      Polish children aged 7-18 years were presented. * The analysis shows how gender
      and socioeconomics determinants influence the prevalence of thinness among
      children and adolescent in post-transformation country and can be used to
      international comparisons.

PMID- 28451760
TI  - Reconstruction of LGT networks from tri-LGT-nets.
AB  - Phylogenetic networks have gained attention from the scientific community due to
      the evidence of the existence of evolutionary events that cannot be represented
      using trees. A variant of phylogenetic networks, called LGT networks, models
      specifically lateral gene transfer events, which cannot be properly represented
      with generic phylogenetic networks. In this paper we treat the problem of the
      reconstruction of LGT networks from substructures induced by three leaves, which
      we call tri-LGT-nets. We first restrict ourselves to a class of LGT networks that
      are both mathematically treatable and biologically significant, called BAN-LGT
      networks. Then, we study the decomposition of such networks in subnetworks with
      three leaves and ask whether or not this decomposition determines the network.
      The answer to this question is negative, but if we further impose time
      consistency (species involved in a later gene transfer must coexist) the answer
      is affirmative, up to some redundancy that can never be recovered but is fully
      characterized.

PMID- 28451761
TI  - Clinicopathological Significance and Prognosis of Medullary Thyroid
      Microcarcinoma: A Meta-analysis.
AB  - BACKGROUND: The objective of the present meta-analysis was to evaluate the
      clinicopathological significance and prognosis of micro-MTC compared to macro
      MTC. METHODS: Relevant articles were obtained by searching the PubMed and MEDLINE
      databases. A meta-analysis was performed using 15 eligible studies. In addition,
      subgroup analysis based on heredity was performed in patients diagnosed with
      micro-MTC. RESULTS: The rate of extrathyroidal extension of micro-MTC [0.118 (95%
      CI 0.073-0.185)] was significantly lower than that of macro-MTC [0.303 (95% CI
      0.224-0.395)]. Micro-MTC [0.229 (95% CI 0.161-0.314)] had a significantly lower
      rate of cervical lymph node (LN) metastasis compared to macro-MTC [0.595 (95% CI
      0.486-0.694)]. The rate of multifocality was not significantly different between
      micro-MTC and macro-MTC [0.394 (95% CI 0.244-0.566) vs. 0.320 (95% CI 0.234
      0.421), respectively]. The rate of distant metastasis did not differ
      significantly between micro-MTC [0.082 (95% CI 0.017-0.314)] and macro-MTC [0.068
      (95% CI 0.009-0.376)]. Patients with micro-MTC showed significantly higher
      disease-free survival rates [hazard ratio [HR] 0.406 (95% CI 0.288-0.575), I 2 =
      40.563%] compared to patients with macro-MTC. CONCLUSION: Micro-MTC has
      aggressive features, such as multifocality and distant metastasis, similar to
      macro-MTC and a non-negligible rate of extrathyroidal extension and cervical LN
      metastasis. We suggest that treatment of micro-MTC should be approached with a
      similar focus as that of macro-MTC. Considering that less extrathyroidal
      extension and cervical LN metastasis occur in patients with micro-MTC compared to
      macro-MTC, we propose that treatment of micro-MTC, which has a relatively low
      disease burden status, should be viewed as an opportunity for improving
      prognosis.

PMID- 28451762
TI  - Postoperative Prolonged Inflammatory Response as a Poor Prognostic Factor After
      Curative Resection for Gastric Cancer.
AB  - BACKGROUND: Postoperative inflammatory complications are associated with poorer
      prognosis in gastrointestinal malignancies. The aims of this study were to
      clarify the impact of postoperative inflammation itself on overall survival (OS)
      and relapse-free survival (RFS) in advanced gastric cancer patients. METHODS: We
      retrospectively analyzed 490 patients who underwent curative resection for pStage
      II and III gastric cancer from 2005 to 2008. We evaluated postoperative
      inflammation based on duration of hyperthermia (body temperature >=38  degrees C)
      and leukocytosis (>=12,000/uL-1). OS and RFS were compared between a prolonged
      inflammation group and non-prolonged inflammation group. Multivariate analysis
      using the Cox proportional hazard model was performed to identify independent
      prognostic factors. RESULTS: The prolonged inflammation group comprised 57
      (11.7%) patients who had hyperthermia for 4 days or longer and 42 (8.6%) patients
      who had leukocytosis for 7 days or longer. OS and RFS were significantly worse in
      the prolonged hyperthermia group (OS: hazard ratio (HR) 1.84, 95% confidence
      interval (CI) 1.19-2.73, P = 0.004; RFS: HR 1.66, 95% CI 1.08-2.45, P = 0.015).
      The prolonged leukocytosis group also showed significantly worse OS (HR 1.92, 95%
      CI 1.19-2.96, P = 0.004) and RFS (HR 1.90, 95% CI 1.19-2.88, P = 0.004).
      Multivariate analysis identified prolonged hyperthermia as an independent factor
      for predicting poor prognosis (OS: HR 1.77, 95% CI 1.13-2.68, P = 0.013; RFS: HR
      1.60; 95% CI 1.03-2.39, P = 0.038). CONCLUSIONS: Prolonged hyperthermia and
      leukocytosis after curative gastrectomy were associated with poorer OS and RFS in
      advanced gastric cancer patients.

PMID- 28451763
TI  - Evaluating the performance of PI-RADS v2 in the non-academic setting.
AB  - PURPOSE: To evaluate the utility of PI-RADS v2 to diagnose clinically significant
      prostate cancer (CS-PCa) with magnetic resonance ultrasound (MR/US) fusion-guided
      prostate biopsies in the non-academic setting. MATERIALS/METHODS: Retrospective
      analysis of men whom underwent prostate multiparametric MRI and subsequent MR/US
      fusion biopsies at a single non-academic center from 11/2014 to 3/2016. Prostate
      MRIs were performed on a 3-Tesla scanner with a surface body coil. The Prostate
      Imaging Reporting and Data System (PI-RADS) v2 scoring algorithm was utilized and
      MR/US fusion biopsies were performed in selected cases. Mixed effect logistic
      regression analyses and receiver-operating characteristic (ROC) curves were
      performed on PI-RADS v2 alone and combined with PSA density (PSAD) to predict CS
      PCa. RESULTS: 170 patients underwent prostate MRI with 282 PI-RADS lesions. MR/US
      fusion diagnosed 71 CS-PCa, 33 Gleason score 3+3, and 168 negative. PI-RADS v2
      score is a statistically significant predictor of CS-PCa (P < 0.001). For each
      one-point increase in the overall PI-RADS v2 score, the odds of having CS-PCa
      increases by 4.2 (95% CI 2.2-8.3). The area under the ROC curve for PI-RADS v2 is
      0.69 (95% CI 0.63-0.76) and for PI-RADS v2 + PSAD is 0.76 (95% CI 0.69-0.82),
      statistically higher than PI-RADS v2 alone (P < 0.001). The rate of CS-PCa was
      about twice higher in men with high PSAD (>=0.15) compared to men with low PSAD
      (<0.15) when a PI-RADS 4 or 5 lesion was detected (P = 0.005). CONCLUSION: PI
      RADS v2 is a strong predictor of CS-PCa in the non-academic setting and can be
      further strengthened when utilized with PSA density.

PMID- 28451764
TI  - MDCT of the liver in obese patients: evaluation of a different method to optimize
      iodine dose.
AB  - PURPOSE: To prospectively compare two different approaches for estimating the
      amount of intravenous contrast media (CM) needed for multiphasic MDCT of the
      liver in obese patients. MATERIALS AND METHODS: This single-center, HIPAA
      compliant prospective study was approved by our Institutional Review Board.
      Ninety-six patients (55 men, 41 women), with a total of 42 hypovascular liver
      lesions, underwent MDCT of the liver. The amount of contrast medium injected was
      computed according to the patient's lean body weight which was estimated using
      either a bioimpedance device (Group A) or the James formula (Group B). The
      following variables were compared between the two groups: the amount of contrast
      medium injected (in grams of Iodine, gI), the contrast enhancement index (CEI)
      and the lesion-to-liver contrast-to-noise ratio. RESULTS: Protocols A and B
      yielded significant differences in the amount of CM injected (mean values 41.9 +/
      4.41 gI in Group A vs. 35.9 +/- 5.75 gI in Group B; P = 0.021). The mean CEI
      value and lesion-to-liver contrast-to-noise ratio measured on the portal phase
      were significantly higher with protocol A than with protocol B (P < 0.05).
      CONCLUSIONS: Our study shows that the adoption of a bioimpedance device in obese
      patients improves liver parenchymal enhancement and lesion conspicuity.

PMID- 28451765
TI  - Parkinsonism and high-intensity midbrain lesions on T2-weighted imaging in
      hepatic encephalopathy: a case report.

PMID- 28451766
TI  - Sacral neurostimulation for low anterior resection syndrome after radical
      resection for rectal cancer: evaluation of treatment with the LARS score.
AB  - PURPOSE: Sacral neurostimulation (SNS) has proven to be an effective treatment
      modality for low anterior resection syndrome (LARS). The primary aim of this
      study is to investigate the impact of SNS on all symptoms of LARS, not merely on
      fecal incontinence. Furthermore, we wanted to evaluate whether the LARS score
      could be useful as a tool to evaluate SNS treatment. METHODS: All patients
      diagnosed with minor or major LARS, unresponsive to conservative therapy for
      fecal incontinence, who underwent sacral neuromodulation for LARS at Groeninge
      Hospital, Kortrijk, Belgium, were prospectively enrolled in the study. The
      primary endpoint was the reduction in the severity of LARS. This was assessed by
      validated questionnaires: the LARS score and the Wexner score. RESULTS: Eleven
      patients underwent definite implantation of the SNS device. All patients showed a
      substantial decrease in their Wexner scores: The mean score was reduced from 17.7
      to 4.6 (Z: 2.93; p: 0.0033). Additionally, the mean LARS score dropped from 36.9
      to 11.4 (Z: 2.93; p: 0.0033). Furthermore, there was a significant amelioration
      of all symptoms of LARS. CONCLUSIONS: Our study shows that SNS is effective for
      all symptoms of LARS. The authors believe that in patients who receive SNS for
      LARS, it could be useful to determine the LARS score to evaluate the complexity
      of the symptoms and their response to treatment.

PMID- 28451767
TI  - Distal Doppler-guided transanal hemorrhoidal dearterialization with mucopexy
      versus conventional hemorrhoidectomy for grade III and IV hemorrhoids:
      postoperative morbidity and long-term outcomes.
AB  - BACKGROUND: Distal Doppler-guided transanal hemorrhoidal dearterialization with
      mucopexy (Doppler-guided THD) seems to be associated with better short-term
      outcomes than conventional hemorrhoidectomy, but there are little data about long
      term recurrence. The aim of this study was to compare Doppler-guided THD for
      grade III-IV hemorrhoids with conventional hemorrhoidectomy with regard to long
      term postoperative morbidity and recurrence. METHODS: This was a single-center
      longitudinal and comparative study of a cohort of patients who underwent either
      distal Doppler-guided THD with low ligation of the hemorrhoidal artery and
      mucopexy or conventional excisional hemorrhoidectomy (Milligan and Morgan or
      Ferguson) for grade III and IV hemorrhoids. Short- and long-term postoperative
      morbidity was recorded. Severity of hemorrhoid symptoms (bleeding, prolapse,
      manual reduction, discomfort or pain and impact on quality of life) and fecal
      continence status (Vaizey score) were evaluated before surgery and at minimum of
      1 year after surgery. RESULTS: Eighty-three patients were included in the study.
      Forty-nine patients (59%) underwent Doppler-guided THD, and 34 (41%) patients
      underwent conventional hemorrhoidectomy. The 30-day postoperative surgical
      morbidity was 26.5% in the Doppler-guided THD group and 8.82% in the conventional
      hemorrhoidectomy group (p = 0.085). No significant differences between the groups
      were observed in terms of persistence of bleeding, prolapse, need for manual
      reduction in prolapse and pain. One (2%) patient in the THD group and 2 (5.4%)
      patients in the conventional hemorrhoidectomy group needed further surgical
      procedures. Minor fecal incontinence occurred only after conventional
      hemorrhoidectomy in 2 (5.4%) patients. CONCLUSIONS: Our results showed that
      Doppler-guided THD is not inferior to conventional excisional hemorrhoidectomy
      for advanced hemorrhoidal disease in terms of postoperative complications and
      long-term recurrence of symptoms.

PMID- 28451768
TI  - Invasive planktivores as mediators of organic matter exchanges within and across
      ecosystems.
AB  - Bighead carp (Hypophthalmichthys nobilis) are an invasive planktivore that can
      greatly deplete planktonic resources. Due to the inefficient conversion of food
      into fish tissue, large portions of consumed materials are egested and shunted to
      benthic habitats. We explored how bighead carp alter pools of organic matter
      between planktonic and benthic habitats, and across ecosystem boundaries. Here,
      we report evidence from a manipulative experiment demonstrating that bighead carp
      greatly reapportion pools of organic matter from planktonic to benthic habitats
      to such a degree that additional effects propagated across ecological boundaries
      into terrestrial ecosystems. Strong direct consumption by bighead carp reduced
      filamentous algae, biomass and production of zooplankton, and production of a
      native planktivorous fish within planktonic habitats. Reduced herbivory
      indirectly increased phytoplankton (chlorophyll a). Direct consumption of organic
      matter by bighead carp supported high carp production and concomitant losses of
      materials due to egestion. Perhaps in response to organic matter subsidies
      provided by fish egestion, ponds having bighead carp had higher standing crop
      biomass of Chironomidae larvae, as well as cross-boundary fluxes of their adult
      life stage. In contrast, we detected reduced cross-boundary fluxes of adult
      Chaoboridae midges in ponds having bighead carp. Consideration of bighead carp as
      mediators of organic matter exchanges provides a clearer framework for predicting
      the direct and extended impacts of these invasive planktivores in freshwater
      ecosystems. The perception of bighead carp must evolve beyond competitors for
      planktonic resources, to mediators and processors of nutrients and energy within
      and across ecosystems.

PMID- 28451769
TI  - Cellular thermotolerance is independent of HSF 1 expression in zebu and crossbred
      non-lactating cattle.
AB  - Heat stress is an important domain of research in livestock due to its negative
      impact on production and disease resistance. The augmentation of stress in the
      body stimulates the antioxidative activity comprising various enzymes (viz.,
      catalase, superoxide dismutase), metabolites (reduced glutathione, etc.),
      vitamins, minerals, etc. to combat the situation. The major key players involved
      in regulation of heat shock response in eukaryotes are the transcription factors,
      called as heat shock factors (HSF). They activate the heat shock protein (HSP)
      genes by binding to their promoters. Lymphocytes are considered to be the best
      model to evaluate the immunity in any living body as it contains plethora of
      white blood cells (WBCs).In this study, the peripheral blood mononuclear cells
      (PBMC) obtained from non-lactating Sahiwal vis-a-vis crossbred (Holstein Friesian
      * Sahiwal) cattle with 75% or more exotic inheritance were subjected to heat
      shock at 39, 41, and 43  degrees C in three different incubators, in vitro. The
      cell count and viability test of pre and post heat stress of concerned PBMCs
      indicated that the crossbreeds are more prone to heat stress as compared to
      Sahiwal. The reverse transcription PCR (qRT-PCR) expression data revealed an
      increment in HSF1 expression at 41  degrees C which subsequently declined (non
      significantly) at 43  degrees C in both breeds post 1 h heat shock. However, the
      association between the HSF 1 expression and antioxidative activity through
      correlation analysis was found to be non-significant (P < 0.05), though enzymatic
      activity appeared to behave in a similar fashion in both breeds at 5% level of
      significance (P < 0.05). This rule out the role of HSF1 expression level on the
      activity of enzymes involved in oxidative stress in vitro in zebu and crossbred
      cattle.

PMID- 28451770
TI  - Multi-modality imaging of the leaking ureter: why does detection of traumatic and
      iatrogenic ureteral injuries remain a challenge?
AB  - Ureteral injuries are uncommon in trauma patients, accounting for fewer than 1%
      of all injuries to the urinary tract. These uncommon, yet problematic, injuries
      can often be overlooked in the standard search pattern on abdominal and pelvic
      multi-detector CT (MDCT) images, as radiologists focus on more immediate life
      threatening injuries. However, early diagnosis and management are vital to reduce
      potential morbidity. If there is a high clinical index of suspicion for ureteral
      injuries with penetrating or blunt trauma, or if there is suspected iatrogenic
      ureteral injury, delayed-phase/urographic-phase MDCT images are essential for
      confirming the diagnosis. Moreover, making the distinction between partial and
      complete ureteral transection is critical, as it will guide management. The aim
      of this pictorial review is to overview the key imaging findings in blunt and
      penetrating traumatic and iatrogenic injuries of the ureter, as well as to
      discuss the advantages and disadvantages of different imaging modalities for
      accurately and rapidly establishing or excluding the diagnosis of ureteral
      injuries, with an emphasis on MDCT. The potential causes of missed ureteral
      injuries will also be discussed.

PMID- 28451772
TI  - The ten barriers for translation of animal data on AKI to the clinical setting.

PMID- 28451771
TI  - Epistatic determinism of durum wheat resistance to the wheat spindle streak
      mosaic virus.
AB  - KEY MESSAGE: The resistance of durum wheat to the Wheat spindle streak mosaic
      virus (WSSMV) is controlled by two main QTLs on chromosomes 7A and 7B, with a
      huge epistatic effect. Wheat spindle streak mosaic virus (WSSMV) is a major
      disease of durum wheat in Europe and North America. Breeding WSSMV-resistant
      cultivars is currently the only way to control the virus since no treatment is
      available. This paper reports studies of the inheritance of WSSMV resistance
      using two related durum wheat populations obtained by crossing two elite
      cultivars with a WSSMV-resistant emmer cultivar. In 2012 and 2015, 354
      recombinant inbred lines (RIL) were phenotyped using visual notations, ELISA and
      qPCR and genotyped using locus targeted capture and sequencing. This allowed us
      to build a consensus genetic map of 8568 markers and identify three chromosomal
      regions involved in WSSMV resistance. Two major regions (located on chromosomes
      7A and 7B) jointly explain, on the basis of epistatic interactions, up to 43% of
      the phenotypic variation. Flanking sequences of our genetic markers are provided
      to facilitate future marker-assisted selection of WSSMV-resistant cultivars.

PMID- 28451773
TI  - Correlation between three-dimensional power Doppler and morphometric measurement
      of endometrial vascularity at the time of embryo implantation in women with
      unexplained recurrent miscarriage.
AB  - Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has
      been used as a noninvasive tool to evaluate the vascularity. However, it is
      unclear whether 3D-PD can accurately reflect endometrial vascularization and
      replace the invasive endometrial biopsy. This study aims to investigate the
      correlation between 3D-PD and micro vessel morphometric measurement of
      endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage
      were recruited for 3D-PD and endometrial biopsy on precisely day LH + 7.
      Immunohistochemistry using vWF was employed to identify micro vessels in
      endometrial biopsy specimens followed by the use of morphometric technique to
      measure the mean vessel diameter and volume fractions. The vascularization index
      (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were
      calculated for both the endometrial and sub-endometrial regions. There were no
      significant correlations between any of the ultrasonographic measurements
      (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub
      endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number
      of micro vessel, mean diameter of micro vessel and volume fraction measurement of
      vessel). This study indicates that endometrial vascularity assessed by 3D-PD
      could not be used to reflect changes in micro vessels of the endometrium at the
      time of embryo implantation in women with unexplained recurrent miscarriage.

PMID- 28451774
TI  - Relationship between left atrium catheter contact force and pacing threshold.
AB  - PURPOSE: The purpose of this study is to analyze the relationship between contact
      force (CF) and pacing threshold in left atrium (LA). METHODS: Six to ten LA sites
      were studied in 28 consecutive patients with atrial fibrillation undergoing
      pulmonary vein isolation. Median CF, bipolar and unipolar electrogram voltage,
      impedance, and bipolar and unipolar thresholds for consistent constant capture
      and for consistent intermittent capture were measured at each site. RESULTS:
      Pacing threshold measurements were performed at 188 LA sites. Both unipolar and
      bipolar pacing thresholds correlated significantly with median CF; however,
      unipolar pacing threshold correlated better (unipolar: Pearson R -0.45; p <
      0.001; Spearman Rho -0.62; p < 0.001, bipolar: Pearson R -0.39; p < 0.001;
      Spearman Rho -0.52; p < 0.001). Consistent constant capture threshold had better
      correlation with median CF than consistent intermittent capture threshold for
      both unipolar and bipolar pacing (Pearson R -0.45; p < 0.001 and Spearman Rho 
      0.62; p < 0.001 vs. Pearson R -0.35; p < 0.001; Spearman Rho -0.52; p < 0.001).
      The best pacing threshold cutoff point to detect a good CF (>10 g) was 3.25 mA
      for unipolar pacing with 69% specificity and 73% sensitivity. Both increased to
      80% specificity and 74% sensitivity for sites with normal bipolar voltage and a
      pacing threshold cutoff value of 2.85 mA. CONCLUSIONS: Pacing thresholds
      correlate with CF in human not previously ablated LA. Since the combination of a
      normal bipolar voltage and a unipolar pacing threshold <2.85 mA provide
      reasonable parameters of validity, pacing threshold could be of interest as a
      surrogate for CF in LA.

PMID- 28451775
TI  - Variations of placental migration in patients with early third trimester
      malposition.
AB  - AIM: This study aimed to investigate the impact of placental migration on the
      definitive prepartum diagnosis of patients with placenta previa (PP) and low
      lying placenta (LLP) after late preterm. METHODS: This was a retrospective cohort
      study of singleton pregnancies with PP and LLP diagnosed at 30-33 weeks of
      gestation. We assessed the rate of changes in transvaginal ultrasonographic
      measurements of placental position during the period from 34 to 38 weeks of
      gestation. RESULTS: A total of 127 cases (82 of PP, 45 of LLP) were included. The
      PP group comprised 34 cases with complete PP and 48 with partial and marginal PP.
      The diagnosis of complete PP was changed to partial or marginal PP in two (5.9%)
      cases. Concerning cases with partial and marginal PP, 14 (29.2%) were eventually
      revised to LLP and four (8.3%) ultimately normalized. Among the patients with
      LLP, placental position was normalized in 23 (51.1%). Overall, a revision in
      diagnosis after late preterm was required in 48 cases (37.8%). Among the 93
      patients who did not have complete PP, 46 (49.5%) needed revisions of their
      placental diagnosis. CONCLUSIONS: Repeated evaluations of placental position by
      ultrasonography after late preterm could be of significant value in selecting the
      most appropriate mode of delivery.

PMID- 28451776
TI  - Acetylsalicylic acid-tris-hydroxymethyl-aminomethane reduces colon mucosal damage
      without causing gastric side effects in a rat model of colitis.
AB  - BACKGROUND: We have developed a novel compound from acetylsalicylic acid (ASA)
      and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors with ASA-like
      anti-inflammatory efficacy and reduced the mucosa-damaging side-effects. Our aim
      was to examine local and remote consequences of ASA-Tris administration in 2-,4
      ,6-trinitrobenzene-sulfonic acid (TNBS)-induced colitis as compared to ASA or
      mesalamine (5-aminosalicylate) treatment. METHODS: Sprague-Dawley rats were
      randomized to five groups (n = 6, each), and TNBS enemas were performed. Group 1
      was the negative control; group 2 was the untreated colitis group. 12 hour after
      colitis induction repeated doses of ASA, ASA-Tris (both 0.55 mmol/kg) and
      mesalamine (0.77 mmol/kg) were given 3 times daily for 3 days to groups 3-5. On
      day 3 of colitis, the in vivo histology of the colon and stomach was
      investigated. Tissue xanthine-oxidoreductase, myeloperoxidase, nitrite/nitrate
      changes, and circulating TNF-alpha levels were measured. In addition, liver
      mitochondria were examined with high-resolution respirometry to analyze
      alterations in the electron transport chain. RESULTS: TNBS enema significantly
      elevated inflammatory enzyme activities, NO production, TNF-alpha concentration,
      and induced morphological damage in the colon. ASA-treatment reduced the
      inflammatory marker levels and mucosal injury in the colon, but gastric tissue
      damage was present. ASA-Tris- and mesalamine-treatments significantly reduced the
      cytokine levels, inflammatory enzyme activities, and colonic mucosal damage
      without inducing gastric injury. Also, ASA significantly reduced the Complex IV
      linked respiration of liver mitochondria, which was not observed after ASA-Tris
      treatment. CONCLUSION: As compared to ASA, ASA-Tris conjugation provides
      significant protection against the colonic injury and cytokine-mediated
      progression of inflammatory events in experimental colitis without influencing
      the gastric epithelial structure.

PMID- 28451777
TI  - Infantile cranial fasciitis: case-based review and operative technique.
AB  - BACKGROUND: Cranial fasciitis (CF) is an uncommon benign primary lesion of the
      skull that typically affects the pediatric age group. Due to the rarity of CF, no
      prospective studies exist. Earliest description of this condition dates to 1980.
      The limited scientific and clinical literature regarding CF is dominated by case
      reports. For these reasons, questions pertaining to the true incidence, genetic
      risk factors, prognosis, and long-term outcome remain unanswered. DISCUSSION:
      Clinically, CF presents as a firm, painless, growing scalp mass that is typically
      not considered in the differential diagnosis. Preoperative pathognomonic signs
      and symptoms are absent, and imaging features are often nonspecific. Treatment is
      typically through complete surgical resection, at which time histopathological
      examination confirms the diagnosis of CF. Reconstruction of the skull defect in
      the child is critical. Autograft techniques help maintain a rigid construct that
      integrates with the native skull while preserving its continued ability to grow.
      Generally, a good outcome is observed with complete resection. EXEMPLARY CASE: We
      report a case of CF in an infant with emphasis on operative nuances and early
      follow-up results. CONCLUSION: CF is a rare fibroproliferative disease that has a
      poorly defined incidence and long-term follow-up. Due to its locally invasive
      nature and nonspecific presentation, CF is often difficult to differentiate from
      malignancies and infections. Complete surgical resection is the best approach for
      diagnosis and cure. Its occult clinical presentation often allows it to achieve
      considerable growth, leaving a sizeable skull defect following resection. Since
      CF presents in the pediatric population, allograft reconstruction is preferred
      over titanium mesh or other synthetic materials to allow osseous integration and
      continued uninterrupted skull growth.

PMID- 28451779
TI  - Arrhythmic risk evaluation in myotonic dystrophy: the importance of selection
      criteria and methodological approach.

PMID- 28451778
TI  - Central nervous system melioidosis in the pediatric age group: review.
AB  - PURPOSE: Melioidosis is a potentially fatal infectious disease caused by
      Burkholderia pseudomallei. Neurologic involvement in pediatric age group is very
      rare, and only a handful of cases have been reported in literature. We sought to
      provide a systematic review of pediatric neurologic melioidosis. METHODS:
      Literature review was performed to analyze reported cases of pediatric neurologic
      melioidosis (<=16 years) by searching online database (PubMed/MEDLINE). RESULTS:
      Twenty-seven cases were analyzed. Mean age was 6.7 years (range 2 days-14 years)
      and around 50% were older children (>5 years). Cranial nerve palsies and fever
      were most common presenting features. Major manifestations were
      meningoencephalitis in 16 (59%) and cerebral abscesses in eight (29%) cases.
      Abscesses were mostly located in parietal lobe. Among older children, abscesses
      were common than meningeal disease, while being converse for neonates. Mean
      follow-up duration was 11.5 months. Ten cases showed good to excellent outcome,
      while eight cases had fair (incomplete recovery) outcomes. The overall mortality
      rate was 18.5% (5/27) and tends to decrease with age. Among the five deaths, 4
      (80%) had septicemia or pneumonia. CONCLUSIONS: Pediatric neurologic melioidosis
      is very rare. Meningoencephalitis is the most common presentation. Mortality is
      the highest in neonates. Ceftazidime appears to be the drug of choice in
      intensive phase, although the best drug in maintenance phase cannot be commented
      upon, especially in very young children.

PMID- 28451781
TI  - 13 novel putative mutations in ATP7A found in a cohort of 25 Italian families.
AB  - ATP7A is a copper-transporting P-type adenosine triphosphatase whose loss of
      function leads to the Menkes disease, an X-linked copper metabolism multi-organ
      disorder (1 in 100.000 births). Here we document our experience with the ATP7A
      linked diseases in Italy. We analyzed the exonic structure of the ATP7A gene in
      25 unrelated Italian families and studied the variants of unknown significance.
      We identified 22 different DNA alterations, 13 of which first reported in this
      study. The classical Menkes phenotype was present in 21 of the 25 families and
      was linked with highly damaging mutations (7 nonsense; 4 frame-shift; 2 small in
      frame deletions, 2 splice site alterations, 2 gross deletions, and 1 gross
      duplication). Of the 4 cases with milder variants of the Menkes disease two had a
      missense mutation, one a leaky splice site alteration and one a nonsense mutation
      in exon 22. We determined in silico that all the mutations leading to the
      classical Menkes disease leave no residual activity of ATP7A including the
      apparently less severe in-frame deletions. Whereas milder forms of the disease
      are characterized by mutations that allow a limited residual activity of ATP7A,
      including the nonsense mutation observed.

PMID- 28451782
TI  - Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular
      uptake, and cellular localization.
AB  - Recently, we have characterized the DNA and nucleoprotein (NP) binding of bis(4-N
      methylpyridyl)-15,20-di(4-carboxyphenyl)porphyrin (BMPCP) and meso-tri(4-N
      methylpyridyl)-mono(4-carboxyphenyl)porphyrin (TMPCP) and their tetrapeptide
      conjugates (BMPCP-4P2 and TMPCP-4P, respectively). In this work, we investigated
      the interaction of TMPCP conjugated to the tetrapeptide branches of branched
      chain polymeric polypeptide with poly-L-lysine backbone (AK) with DNA or NP using
      spectroscopic methods. Analysis of absorption spectra revealed the external
      binding but no intercalation of TMPCP-AK to DNA. There was no evidence for the
      interaction between TMPCP-AK and encapsidated DNA. Furthermore, we examined the
      cellular uptake of BMPCP and TMPCP and their tetra- or polypeptide conjugates by
      flow cytometry and analyzed how charge, size, and structure of the compounds
      affect their incorporation. In comparison, liposomal association constants of
      these derivatives were determined. BMPCP-4P2 accumulated the most, and porphyrins
      with two positive charges (BMPCP and BMPCP-4P2) showed better accumulation than
      the tri-cationic TMPCP or TMPCP-4P. Cellular uptake of polycationic TMPCP-AK was
      significantly lower than that of the free or tetrapeptide conjugated derivatives.
      The subcellular localization of all the five compounds was investigated in co
      localization studies by confocal microscopy with special attention to their
      nuclear localization. Neither free nor conjugated BMPCP or TMPCP was co-localized
      with nuclear marker. Instead, these derivatives showed co-localization with
      lysosomal and mitochondrial fluorescent probes. TMPCP-AK conjugate had different
      localization patterns appearing mainly in mitochondria and cytoplasmic vesicles.
      Our results may contribute to the further design of DNA-targeting porphyrin-based
      constructs.

PMID- 28451780
TI  - Effects of repeated restraint stress and WiFi signal exposure on behavior and
      oxidative stress in rats.
AB  - Today, due to technology development and aversive events of daily life, Human
      exposure to both radiofrequency and stress is unavoidable. This study
      investigated the co-exposure to repeated restraint stress and WiFi signal on
      cognitive function and oxidative stress in brain of male rats. Animals were
      divided into four groups: Control, WiFi-exposed, restrained and both WiFi-exposed
      and restrained groups. Each of WiFi exposure and restraint stress occurred 2 h
      (h)/day during 20 days. Subsequently, various tests were carried out for each
      group, such as anxiety in elevated plus maze, spatial learning abilities in the
      water maze, cerebral oxidative stress response and cholinesterase activity in
      brain and serum. Results showed that WiFi exposure and restraint stress, alone
      and especially if combined, induced an anxiety-like behavior without impairing
      spatial learning and memory abilities in rats. At cerebral level, we found an
      oxidative stress response triggered by WiFi and restraint, per se and especially
      when combined as well as WiFi-induced increase in acetylcholinesterase activity.
      Our results reveal that there is an impact of WiFi signal and restraint stress on
      the brain and cognitive processes especially in elevated plus maze task. In
      contrast, there are no synergistic effects between WiFi signal and restraint
      stress on the brain.

PMID- 28451783
TI  - Selenium Supplementation Changes the Ion Profile in the Pancreas of Chickens
      Treated with Cadmium.
AB  - Increasing evidence indicates that selenium (Se) could antagonize metal toxicity,
      including cadmium (Cd) toxicity. However, the effects of Se on Cd-induced changes
      in the ion profile in the pancreas of chickens have not been reported. In the
      present study, 128 Hy-Line brown laying chickens were divided into the control
      group, Se-treated group, Se/Cd-treated group, and Cd-treated group, and we
      detected the concentrations of 28 ions in the four groups by inductively coupled
      plasma mass spectrometry. In the Cd-treated group, the accumulation of Cd in the
      pancreas was 836.8 times higher that than in the control group (27,353.71
      ppb/32.69 ppb). Meanwhile, the Ca, Ti, Fe, Mo, Li, Al, and Pb levels increased
      and the Cr, Mn, Ni, Cu, Zn, Se, Sr, and Sb levels decreased due to sub-chronic Cd
      poisoning. The Fe, Mo, Ba, and Pb levels decreased in the Se/Cd-treated group.
      Our findings suggest that Cd can accumulate in the chicken pancreas and affect
      the ion profiles, whereas Se can ameliorate the accumulation of Cd and change the
      ion profiles in the chicken pancreas.

PMID- 28451784
TI  - Pre-existing low-back symptoms impact adversely on sitting time reduction in
      office workers.
AB  - OBJECTIVES: Initiatives to reduce office-workplace sitting are proliferating, but
      the impact of pre-existing musculoskeletal symptoms on their effectiveness has
      not been determined. We assessed the influence of musculoskeletal symptoms on the
      outcomes of a workplace sitting intervention. METHODS: Baseline and 3-month data
      from a cluster-randomized controlled trial of a workplace sitting intervention
      (Stand Up Victoria; trial registration number ACTRN12611000742976) were used.
      Office workers (n = 231) from 14 work teams within one organisation were
      randomised (by worksite) to a multicomponent program with individual-,
      organisational-, and environmental-level (sit-stand workstations) change
      strategies; or, to a control condition (no intervention). Musculoskeletal
      symptoms in the low-back, upper and lower extremities (present/absent) were
      assessed through self-report. Linear regression models tested the moderation by
      baseline musculoskeletal symptoms of intervention effects on workplace sitting
      and standing time and on sitting and standing bout durations, assessed by the
      activPAL3TM activity monitor. RESULTS: There were significant reductions in
      sitting and increased standing at work (p < 0.05). However, effects varied
      significantly by the presence of pre-existing low-back (but not other) symptoms,
      with greater benefit being seen in those without symptoms. Effects on sitting
      time and sitting bout duration were weaker in those with low-back symptoms
      compared to those without by 34.6 [95% CI (0.9; 68.3)] min/8-h workday and 5.1
      [95% CI (0.2; 9.9)] min, respectively. Comparable effects were seen for standing.
      CONCLUSION: Low-back symptoms may impact on the extent to which office workers
      change their workplace sitting and standing time. A prudent next step to improve
      the effectiveness of workplace sitting-reduction initiatives such as Stand Up
      Victoria may be to assess and address the needs of those who displayed
      comparatively limited behaviour change, namely those with pre-existing low-back
      discomfort.

PMID- 28451785
TI  - Environmental factors and hormones in the development of rheumatoid arthritis.
AB  - The etiopathogenesis of rheumatoid arthritis (RA) is partially understood.
      Genetic, environmental, and hormonal factors and their interactions are
      considered to play an important role on disease development. The relative
      contribution of environmental factors to RA development is probably larger than
      previously thought. The aim of this review is to appraise robust evidence about
      the role of environmental and hormonal risk factors for RA. We will discuss
      inhaled pollutants, nutritional habits, infectious, hormonal, and reproductive
      factors. As some of these factors are potentially modifiable, understanding their
      impact on RA development opens new opportunities for potential interventions and
      disease prevention.

PMID- 28451786
TI  - The meteorology of cytokine storms, and the clinical usefulness of this
      knowledge.
AB  - The term cytokine storm has become a popular descriptor of the dramatic harmful
      consequences of the rapid release of polypeptide mediators, or cytokines, that
      generate inflammatory responses. This occurs throughout the body in both non
      infectious and infectious disease states, including the central nervous system.
      In infectious disease it has become a useful concept through which to appreciate
      that most infectious disease is not caused directly by a pathogen, but by an
      overexuberant innate immune response by the host to its presence. It is less
      widely known that in addition to these roles in disease pathogenesis these same
      cytokines are also the basis of innate immunity, and in lower concentrations have
      many essential physiological roles. Here we update this field, including what can
      be learned through the history of how these interlinking three aspects of biology
      and disease came to be appreciated. We argue that understanding cytokine storms
      in their various degrees of acuteness, severity and persistence is essential in
      order to grasp the pathophysiology of many diseases, and thus the basis of newer
      therapeutic approaches to treating them. This particularly applies to the
      neurodegenerative diseases.

PMID- 28451788
TI  - The role of autoantibodies in the pathophysiology of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint
      inflammation. The presence of autoantibodies in the sera of RA patients has
      provided many clues to the underlying disease pathophysiology. Based on the
      presence of several autoantibodies like rheumatoid factor (RF), anti
      citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies
      (anti-CarP), and more recently anti-acetylated protein antibodies RA can be
      subdivided into seropositive and seronegative disease. The formation of these
      autoantibodies is associated with both genetic and environmental risk factors for
      RA, like specific human leukocyte antigen (HLA) alleles and smoking.
      Autoantibodies can be detected many years before disease onset in a subset of
      patients, suggesting a sequence of events in which the first autoantibodies
      develop in predisposed hosts, before an inflammatory response ensues leading to
      clinically apparent arthritis. Research on the characteristics and effector
      functions of these autoantibodies might provide more insight in
      pathophysiological processes underlying arthritis in RA. Recent data suggests
      that ACPA might play a role in perpetuating inflammation once it has developed.
      Furthermore, pathophysiological mechanisms have been discovered supporting a
      direct link between the presence of ACPA and both bone erosions and pain in RA
      patients. In conclusion, investigating the possible pathogenic potential of
      autoantibodies might lead to improved understanding of the underlying
      pathophysiological processes in rheumatoid arthritis.

PMID- 28451787
TI  - Future therapeutic targets in rheumatoid arthritis?
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      persistent joint inflammation. Without adequate treatment, patients with RA will
      develop joint deformity and progressive functional impairment. With the
      implementation of treat-to-target strategies and availability of biologic
      therapies, the outcomes for patients with RA have significantly improved.
      However, the unmet need in the treatment of RA remains high as some patients do
      not respond sufficiently to the currently available agents, remission is not
      always achieved and refractory disease is not uncommon. With better understanding
      of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from
      more selective Janus kinase inhibition, there is a great interest in the
      granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine
      kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and
      dendritic cell-based therapeutics. In this review, we will discuss the
      therapeutic potential of these novel approaches.

PMID- 28451789
TI  - Current Update of Patient-Derived Xenograft Model for Translational Breast Cancer
      Research.
AB  - Despite recent advances in the treatment of patients with breast cancer (BrCa),
      BrCa remains the third leading cause of cancer death for women in the US due to
      intrinsic or acquired resistance to therapy. Continued understanding of gene
      expression profiling and genomic sequencing has clarified underlying intratumoral
      molecular heterogeneity. Recently, the patient-derived xenograft (PDX) models
      have emerged as a novel tool to address the issues of BrCa genomics and tumor
      heterogeneity, and to critically transform translational BrCa research in the
      preclinical setting. PDX models are generated by xenografting cancer tissue
      fragments obtained from patients to immune deficient mice, and can be passaged
      into next generations of mice. Generally, in contrast to conventional xenograft
      using cancer cell lines, PDXs are biologically more stable and recapitulate the
      individual tumor morphology, gene expression, and drug susceptibility of each
      patient. PDX may better model the original patient's tumor by retaining tumor
      heterogeneity, gene expression, and similar response to treatment. PDX models are
      thus thought to be more translationally relevant, especially as a drug
      development tool, because PDXs can capture the genetic character and
      heterogeneity that exists within a single patient's tumor and across a population
      of patients' tumors. PDX models also hold enormous potential for identifying
      predictive markers for therapeutic response. It has been repeatedly shown that
      PDX models demonstrate similar levels of activity as compared to the clinical
      response to therapeutic interventions. Therefore, this enables identification of
      therapeutic interventions that can most likely benefit a patient. This allows us
      to address the issues of BrCa genomics and tumor heterogeneity using PDXs in "pre
      clinical" trials. Herein, we reviewed recent scientific development and future
      perspectives using PDX models in BrCa.

PMID- 28451790
TI  - HPV16 E7 DNA tattooing: safety, immunogenicity, and clinical response in patients
      with HPV-positive vulvar intraepithelial neoplasia.
AB  - BACKGROUND: Usual type vulvar intraepithelial neoplasia (uVIN) is caused by HPV,
      predominantly type 16. Several forms of HPV immunotherapy have been studied,
      however, clinical results could be improved. A novel intradermal administration
      route, termed DNA tattooing, is superior in animal models, and was tested for the
      first time in humans with a HPV16 E7 DNA vaccine (TTFC-E7SH). METHODS: The trial
      was designed to test safety, immunogenicity, and clinical response of TTFC-E7SH
      in twelve HPV16+ uVIN patients. Patients received six vaccinations via DNA
      tattooing. The first six patients received 0.2 mg TTFC-E7SH and the next six 2 mg
      TTFC-E7SH. Vaccine-specific T-cell immunity was evaluated by IFNgamma-ELISPOT and
      multiparametric flow cytometry. RESULTS: Only grade I-II adverse events were
      observed upon TTFC-E7SH vaccination. The ELISPOT analysis showed in 4/12 patients
      a response to the peptide pool containing shuffled E7 peptides. Multiparametric
      flow cytometry showed low CD4+ and/or CD8+ T-cell responses as measured by
      increased expression of PD-1 (4/12 in both), CTLA-4 (2/12 and 3/12), CD107a (5/12
      and 4/12), or the production of IFNgamma (2/12 and 1/12), IL-2 (3/12 and 4/12),
      TNFalpha (2/12 and 1/12), and MIP1beta (3/12 and 6/12). At 3 months follow-up, no
      clinical response was observed in any of the twelve vaccinated patients.
      CONCLUSION: DNA tattoo vaccination was shown to be safe. A low vaccine-induced
      immune response and no clinical response were observed in uVIN patients after
      TTFC-E7SH DNA tattoo vaccination. Therefore, a new phase I/II trial with an
      improved DNA vaccine format is currently in development for patients with uVIN.

PMID- 28451791
TI  - Tumor-associated fibrosis as a regulator of tumor immunity and response to
      immunotherapy.
AB  - Tumor-associated fibrosis is characterized by unchecked pro-fibrotic and pro
      inflammatory signaling. The components of fibrosis including significant numbers
      of cancer-associated fibroblasts, dense collagen deposition, and extracellular
      matrix stiffness, are well appreciated regulators of tumor progression but may
      also be critical regulators of immune surveillance. While this suggests that the
      efficacy of immunotherapy may be limited in highly fibrotic cancers like
      pancreas, it also suggests a therapeutic opportunity to target fibrosis in these
      tumor types to reawaken anti-tumor immunity. This review discusses the mechanisms
      by which fibrosis might subvert tumor immunity and how to overcome these
      mechanisms.

PMID- 28451792
TI  - KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung
      adenocarcinoma.
AB  - It was reported that PD-L1 expression was correlated with genetic alterations.
      Whether PD-L1 was regulated by mutant Kirsten rat sarcoma viral oncogene homolog
      (KRAS) in non-small-cell lung cancer (NSCLC) and the underlying molecular
      mechanism were largely unknown. In this study, we investigated the correlation
      between PD-L1 expression and KRAS mutation and the functional significance of PD
      1/PD-L1 blockade in KRAS-mutant lung adenocarcinoma. We found that PD-L1
      expression was associated with KRAS mutation both in the human lung
      adenocarcinoma cell lines and tissues. PD-L1 was up-regulated by KRAS mutation
      through p-ERK but not p-AKT signaling. We also found that KRAS-mediated up
      regulation of PD-L1 induced the apoptosis of CD3-positive T cells which was
      reversed by anti-PD-1 antibody (Pembrolizumab) or ERK inhibitor. PD-1 blocker or
      ERK inhibitor could recover the anti-tumor immunity of T cells and decrease the
      survival rates of KRAS-mutant NSCLC cells in co-culture system in vitro. However,
      Pembrolizumab combined with ERK inhibitor did not show synergistic effect on
      killing tumor cells in co-culture system. Our study demonstrated that KRAS
      mutation could induce PD-L1 expression through p-ERK signaling in lung
      adenocarcinoma. Blockade of PD-1/PD-L1 pathway may be a promising therapeutic
      strategy for human KRAS-mutant lung adenocarcinoma.

PMID- 28451794
TI  - Comparison of long-term prognosis and relapse of dermatomyositis complicated with
      interstitial pneumonia according to autoantibodies: anti-aminoacyl tRNA
      synthetase antibodies versus anti-melanoma differentiation-associated gene 5
      antibody.
AB  - The aim of this study was to investigate long-term prognosis and relapse of
      dermatomyositis complicated with interstitial pneumonia (DMIP) according to anti
      aminoacyl tRNA synthetase (ARS) antibodies and anti-melanoma differentiation
      associated gene 5 (MDA5) antibody. This retrospective study comprised 36 patients
      with DMIP who were divided into the anti-ARS antibody-positive group (ARS+) (n =
      12), anti MDA5 antibody-positive group (MDA5+) (n = 11), double-negative group
      (ARS-/MDA5-) (n = 11), and double-positive group (ARS+/MDA5+) (n = 1). Clinical
      features, treatment, prognoses, and relapses during the 2 years after initiation
      of treatment were compared between three groups excluding ARS+/MDA5+ group.
      Although short-term (24-week) mortality in MDA+ was higher than that in ARS+ or
      ARS-/MDA5- (P = 0.004), there was no difference in long-term (2-year) mortality
      between the three groups. Relapse rate in ARS+ was higher than that in MDA5+ and
      ARS-/MDA5- during the 2 years after initiation of treatment (P = 0.044). There
      was no difference in serum KL-6 levels at the initiation of treatment between
      ARS+ and MDA5+, but serum ferritin levels in MDA5+ were significantly higher than
      those in ARS+ (P = 0.406, 0.042, respectively). Serum KL-6 and ferritin levels at
      2 years after initiation of treatment in ARS+ were significantly higher than
      those in MDA5+ (P = 0.008, 0.034, respectively). We found that in MDA5+ DMIP,
      acute alveolar inflammation caused a poor prognosis early in the disease course,
      and in ARS+ DMIP, chronic injury to the alveolar epithelial cells or basement
      membrane caused long-term recurrence.

PMID- 28451793
TI  - The challenge of the definition of early symptomatic knee osteoarthritis: a
      proposal of criteria and red flags from an international initiative promoted by
      the Italian Society for Rheumatology.
AB  - The aim of this study was to establish consensus for potential early symptomatic
      knee osteoarthritis (ESKOA) clinical definition and referral criteria from
      primary care to rheumatologists, based on available data from literature and a
      qualitative approach, in order to perform studies on patients fulfilling such
      criteria and to validate the obtained ESKOA definition. A complex methodological
      approach was followed including: (1) three focus groups (FG), including expert
      clinicians, researchers and patients; (2) a systematic literature review (SLR);
      (3) two discussion groups followed by a Delphi survey. FG and SLR were performed
      in parallel to inform discussion groups in order to identify relevant constructs
      to be included in the modified Delphi survey. ESKOA is defined in the presence
      of: (a) two mandatory symptoms (knee pain in the absence of any recent trauma or
      injury and very short joint stiffness, lasting for less than 10 min, when
      starting movement) even in the absence of risk factors, or (b) knee pain, and 1
      or 2 risk factors or (c) three or more risk factors in the presence of at least
      one mandatory symptom, with symptoms lasting less than 6 months. These criteria
      are applicable in the absence of active inflammatory arthritis, generalized pain,
      Kellgren-Lawrence grade >0, any recent knee trauma or injury, and age lower than
      40 years. Knee pain in the absence of any recent trauma lasting for less than 6
      months was considered as the referral criterion to the rheumatologist for the
      suspicion of ESKOA. This consensus process has identified provisional clinical
      definition of ESKOA and defined potential referral criterion to rheumatologist,
      in order to test ESKOA obtained definition in prospective validation studies.

PMID- 28451795
TI  - Distribution of osteoarthritis in a Norwegian population-based cohort:
      associations to risk factor profiles and health-related quality of life.
AB  - The objective of the study was to examine the hand-, knee- and hip osteoarthritis
      (OA) distribution, risk factor profiles and health-related quality of life
      (HRQoL) in a population-based OA cohort. Persons with self-reported OA responded
      to questionnaires and attended a clinical examination (N = 606). We analyzed
      cross-sectional associations to risk factor profiles and HRQoL dimensions (Short
      Form 36) in four mutually exclusive groups based on fulfillment of The American
      College of Rheumatology criteria: no OA (NOA), monoarticular upper extremity
      (hand) OA (MOAupper-ex.), monoarticular lower extremity (hip or knee) OA
      (MOAlower-ex.) and polyarticular OA (POA). Multivariate regression analyses and
      correspondence analysis were performed. The distribution of NOA, MOAupper-ex.
      MOAlower-ex. and POA was 21.1, 25.4, 22.4 and 31.0%, respectively. Compared to
      NOA, minor differences were found in risk factor profile in MOAupper-ex., whereas
      POA was significantly associated with sociodemographic, metabolic and mechanical
      features. The correspondence analysis identified different risk factor profiles
      between the four OA phenotypes, but the differences were not statistically
      significant (p = 0.13). Regarding HRQoL, neither OA groups were associated with
      poorer mental functioning. MOAlower-ex. and POA were associated with, among other
      things, poorer physical functioning (beta = -6.2, 95% CI -11.2 to -1.2 and beta =
      -12.5, 95% CI -17.4 to -7.9, respectively) and more pain (beta = -5.4, 95% CI 
      10.4 to -0.3 and beta = -10.5, 95% CI -15.3 to -5.8, respectively). In this
      cohort of persons with self-reported OA, POA was the most prevalent phenotype and
      was associated with an unfortunate risk factor profile and several diminished
      HRQoL dimensions. POA needs further attention in research and clinical care.

PMID- 28451796
TI  - [Psychosocial interventions in inpatient care : Systematic review of the
      effectiveness of universal and selective prevention on mental health].
AB  - BACKGROUND: There are no sufficient findings from synthesized evidence for the
      effectiveness of psychosocial interventions to improve mental health in inpatient
      care. METHODS: A systematic literature search in the databases of MEDLINE, The
      Cochrane Library, EMBASE, CINAHL, and PsycINFO was carried out, as well as a
      manual search in Google Scholar and reference lists. Studies which focused on
      physical or individual activities or therapy or other groups and settings were
      excluded. The heterogeneity of the studies did not allow meta-analysis. RESULTS:
      Seven primary studies were included, whose interventions were assigned to the
      intervention types activation of memories, leisure activities, and social
      participation. Overall, the quality of studies was rather low. Compared to usual
      care or the alternative interventions of memory therapy or leisure activities,
      the positive effects on depressive symptoms, as well as externally assessed and
      self-reported quality of life or life satisfaction, were not significant. The
      absence of these measures lead to deterioration of depressive symptoms among
      residents with dementia. In contrast to memory activation, common leisure
      activities led to an improvement in wellbeing. One intervention for social
      participation increased wellbeing and reduced the occurrence of depressive
      symptoms. CONCLUSION: There is a considerable need for conceptual-theoretical
      work and research on the effectiveness of psychosocial interventions,
      particularly for raising participation among persons in inpatient care
      facilities.

PMID- 28451797
TI  - [Repetitive peripheral muscle stimulation vs. pelvic floor muscle training :
      Comparison of two approaches to incontinence treatment].
AB  - BACKGROUND: Although there are various measures for the prevention, treatment,
      and management of urinary incontinence (UI), absorbing aids (and only scant
      continence-promoting measures) are primarily used in nursing homes in Austria.
      Repetitive peripheral muscle stimulation (RPMS) is already used as a common
      method for the treatment and prevention of incontinence in the outpatient setting
      and is an effective alternative compared to the usual incontinence treatments.
      However, there are no empirical data as yet on the effect of RPMS in nursing home
      residents. AIM: The primary objective of this study was to evaluate and compare
      two forms of UI treatment: RPMS and pelvic floor muscle exercises. MATERIAL AND
      METHODS: To this end, a non-equivalent control group design was used. For the
      purposes of data collection, standardized instruments were used at three points
      of measurement. The sample consisted of 112 people from 22 institutions. RESULTS:
      The severity of UI showed a trend, albeit non-significant, toward improvement in
      both groups. However, a greater increase in quality of life and subjective
      satisfaction with treatment was observed in the RPMS group compared with the
      pelvic floor group. CONCLUSION: Pelvic floor muscle exercises carried out in a
      consistent and well-guided manner show similar effects compared with technology
      assisted therapies. While pelvic floor muscle exercises are feasible in only a
      small proportion of nursing home residents, RPMS training could be a useful
      adjunct to conservative incontinence treatment and is also suitable for
      cognitively impaired individuals. As such, a larger number of elderly individuals
      could gain access to an appropriate and effective incontinence therapy.

PMID- 28451798
TI  - Editor's Invited Commentary on "Discussion: Long-Term Follow-Up of Recurrence and
      Patient Satisfaction After Surgical Treatment of Gynecomastia".

PMID- 28451799
TI  - Micro-autologous Fat Transplantation (MAFT) for Forehead Volumizing and
      Contouring.
AB  - BACKGROUND: Frontal fullness in Asians is often considered to indicate one's
      public popularity and leadership skills. Numerous materials and techniques have
      been applied clinically to recontour or volumize the frontal area, with variable
      results. The micro-autologous fat transplantation (MAFT) technique proposed by
      Lin et al. (2nd academic congress of Taiwan Cosmetic Association Taipei, Taiwan)
      in 2007 has demonstrated its feasibility in facial rejuvenation. In the present
      study, we used an innovative instrument to apply the MAFT technique to frontal
      augmentation with fat grafting and reported the results. METHODS: MAFT was
      performed on 178 patients (167 female, 11 male) during a 5-year period starting
      in January 2010. Fat was harvested by liposuction, processed and refined by
      centrifugation at 1200*g for 3 min. The purified fat was micro-transplanted for
      frontal contouring with the assistance of an instrument, the MAFT-GUN. The
      patients were followed up regularly, and photographs were taken for comparison.
      RESULTS: On average, the MAFT procedure took 52 min to complete. The average
      amount of delivered fat was 10.2 mL. The follow-up period was 34 months on
      average. No complications, including neurovascular injury, skin necrosis,
      abscess, nodulation, calcification or irregularity, were noted. A patient-rated
      satisfaction 5-point Likert scale demonstrated that 83.1% of all patients had
      favorable results (48.3% were satisfied, and 34.8% were very satisfied).
      CONCLUSION: The concept and technique of MAFT has changed fat grafting from an
      operation with unpredictable clinical results to an easy, reliable and consistent
      procedure. Furthermore, the use of a precisely controlled instrument enabled
      surgeons to perform highly accurate micro-fat grafting. In comparison with other
      strategies for volume restoration, the MAFT procedure demonstrated high patient
      satisfaction with the long-term results. Therefore, the use of MAFT as an
      alternative approach to forehead contouring and volumizing was addressed. LEVEL
      OF EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 28451800
TI  - Analysis of the Factors Affecting Men's Attitudes Toward Cosmetic Surgery: Body
      Image, Media Exposure, Social Network Use, Masculine Gender Role Stress and
      Religious Attitudes.
AB  - BACKGROUND: Cosmetic surgery is no longer just for females. More men are opting
      for cosmetic procedures, with marked increases seen in both minimally invasive
      and surgical options over the last decade. Compared to females, relatively little
      work has specifically focused on factors predicting males' attitudes toward
      cosmetic surgery. Therefore, we evaluated a number of variables that may predict
      some facet of men's attitudes toward cosmetic surgery according to evidence
      reported in the literature METHODS: A total of 151 male patients who applied for
      a surgical or minimally invasive cosmetic surgery procedure (patient group) and
      151 healthy male volunteers who do not desire any type of cosmetic procedure
      (control group) were asked to fill out questionnaires about measures of body
      image, media exposure (television and magazine), social network site use,
      masculine gender role stress and religious attitudes. RESULTS: Our findings
      showed that lower ratings of body image satisfaction, increased time spent
      watching television, more frequent social network site use and higher degrees of
      masculine gender role stress were all significant predictors of attitudes toward
      cosmetic surgery among males. CONCLUSION: The current study confirmed the
      importance of body image dissatisfaction as a predictor of the choice to undergo
      cosmetic procedure. More importantly, a new predictor of cosmetic procedure
      attitudes was identified, namely masculine gender role stress. Finally, we
      demonstrated the effects television exposure and social network site use in
      promoting acceptance of surgical and nonsurgical routes to appearance
      enhancement. LEVEL OF EVIDENCE V: This journal requires that authors assign a
      level of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 28451801
TI  - The Characteristics and Short-Term Surgical Outcomes of Adolescent Gynecomastia.
AB  - BACKGROUND: Most adolescent gynecomastia is resolved spontaneously in 3 years.
      But, persistent gynecomastia could have a negative influence on psychoemotional
      development on adolescence. The purpose of this study is to report the
      characteristics of adolescent gynecomastia patients who received the surgeries,
      and discuss the short-term surgical outcomes. METHODS: Of the 1454 patients who
      underwent gynecomastia surgery at Damsoyu hospital from January 2014 to May 2016,
      71 were adolescents. Subcutaneous mastectomy with liposuction was performed for
      adolescent patients who had gynecomastia for more than 3 years and showed
      psychosocial distress. Demographic and outcome variables were retrospectively
      analyzed. RESULTS: The mean age was 17.5 +/- 0.77 years old. All gynecomastia
      cases were bilateral. Simon's grade IIa (35 patients, 49.3%) was the most common,
      and grade III was not observed. Fifty-one patients (71.8%) were classified as
      having a glandular-type breast component. Fourteen patients (19.7%) had
      complications, but only 3 cases (4.2%) required revision. Most of the patients
      (70 patients, 98.6%) were satisfied with the esthetic results, and the average 5
      point Likert score was 4.85 +/- 0.40. Recurrence was not observed. As the Simon's
      grade increased from I to IIA, a higher BMI, larger amounts of breast tissue, and
      longer operation times were observed. CONCLUSIONS: Gynecomastia that did not
      regress spontaneously was mostly the glandular type, so not only liposuction but
      also surgical removal of glandular tissue is necessary. Surgical treatment,
      selectively performed in patients who have had gynecomastia for 3 years, and have
      experienced psychosocial distress, could be an acceptable treatment for
      adolescent gynecomastia. LEVEL OF EVIDENCE IV: This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      evidence-based medicine ratings, please refer to the table of contents or the
      online instructions to authors www.springer.com/00266 .

PMID- 28451803
TI  - Successful second allogeneic stem cell transplantation in a patient with T
      lymphoblastic leukemia (T-ALL) relapsed as myeloid sarcoma.

PMID- 28451802
TI  - Clinical characteristics of patients with central nervous system relapse in BCR
      ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1
      mutations in cerebrospinal fluid.
AB  - We investigated the frequency, predictors, and evolution of acute lymphoblastic
      leukemia (ALL) in patients with CNS relapse and introduced a novel method for
      studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and
      cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analyzed in
      two PETHEMA clinical trials. All achieved complete remission after imatinib
      treatment. Of these, 30 (23%) experienced a relapse after achieving complete
      remission, and 13 (10%) had an isolated CNS relapse or combined CNS and BM
      relapses. We compared the characteristics of patients with and without CNS
      relapse and further analyzed CSF and BM samples from two of the 13 patients with
      CNS relapse. In both patients, classical sequencing analysis of the kinase domain
      of BCR-ABL1 from the cDNA of CSF blasts revealed the pathogenic variant p.L387M.
      We also performed ultra-deep next-generation sequencing (NGS) in three samples
      from one of the relapsed patients. We did not find the mutation in the BM sample,
      but we did find it in CSF blasts with 45% of reads at the time of relapse. These
      data demonstrate the feasibility of detecting BCR-ABL1 mutations in CSF blasts by
      NGS and highlight the importance of monitoring clonal evolution over time.

PMID- 28451804
TI  - Assessment of late cardiomyopathy by magnetic resonance imaging in patients with
      acute promyelocytic leukaemia treated with all-trans retinoic acid and
      idarubicin.
AB  - Late cardiomyopathy CMP is regarded as a potential severe long-term complication
      after anthracycline-based regimens for acute promyelocitic leukaemia (APL). We
      assess by MRI the incidence and severity of clinical and subclinical long-term
      CMP in a cohort of adult APL patients in first complete remission with PETHEMA
      trials. Adult patients diagnosed with APL in first complete remission lasting >=2
      years underwent anamnesis and physical examination and were asked to perform a
      cardiac MRI. Clinical CMP was defined as radiographic and physical signs of heart
      failure accompanied by symptoms or by left ventricle ejection fraction (LVEF)
      <45% by MRI with or without symptoms. Subclinical CMP was defined as the
      following MRI abnormalities: LVEF 45-50% or late gadolinium enhancement or two or
      more of LVEF <=55%, left ventricle end-diastolic volume index >=98 ml/m2, left
      ventricle end-systolic volume index >=38 ml/m2, right ventricle end-diastolic
      volume index >=106 ml/m2 and regional wall motion abnormalities. Of the 82
      patients enrolled in the study, median cumulative dose of anthracyclines
      (doxorubicin equivalence) was 650 mg/m2, and median time from APL diagnosis to
      the study was 87 months (range, 24-195). Seven out of 57 patients with available
      MRI (12%) had subclinical CMP (all of them showed late gadolinium enhancement in
      MRI), and none had clinical CMP. Among the 25 patients without MRI, none had CMP
      by chest X-ray and physical assessment. In summary, we found 12% of subclinical
      and no clinical late CMP assessed by MRI in APL patients treated with PETHEMA
      protocols. Due to the low number of patients, we must interpret our results
      cautiously.

PMID- 28451805
TI  - Role of bone marrow biopsy in staging of patients with classical Hodgkin's
      lymphoma undergoing positron emission tomography/computed tomography.
AB  - Several studies suggested that staging bone marrow biopsy (BMB) could be omitted
      in patients with classical Hodgkin's lymphoma (cHL) when a positron emission
      tomography/computed tomography (PET/CT) is performed at baseline.To address the
      concordance between BMB and PET/CT in the detection of bone marrow involvement
      (BMI) and the BMB role in determining the Ann Arbor stage, we retrospectively
      collected data on 1244 consecutive patients with cHL diagnosed from January 2007
      to December 2013. One thousand eighty-five patients who had undergone both BMB
      and PET/CT were analyzed, comparing the Ann Arbor stage assessed with PET/CT only
      to that resulting from PET/CT combined with BMB.One hundred sixty-nine patients
      (16%) showed at least one focal skeletal lesion (FSL) at PET/CT evaluation. Only
      55 patients had a positive BMB (5.1%); 34 of them presented at least one FSL at
      PET/CT. To the contrary, 895 out of 1030 patients with a negative BMB did not
      show any FSL (86.9%). Positive and negative predictive values of PET/CT for BMI
      were 20 and 98%, respectively; sensitivity and specificity were 62 and 87%,
      respectively. Fifty-four out of 55 patients with a positive BMB could have been
      evaluated as an advanced stage just after PET/CT; only one patient (0.1%) would
      have been differently treated without BMB.Our data showed a very high negative
      predictive value of PET/CT for BMI and a negligible influence of BMB on treatment
      planning, strengthening the recent indications that BMB could be safely omitted
      in cHL patients staged with PET/CT.

PMID- 28451806
TI  - Racial differences in prostate cancer risk in young HIV-positive and HIV-negative
      men: a prospective cohort study.
AB  - PURPOSE: African American men have the highest incidence of prostate cancer among
      ethnic groups, and racial disparity is highest in younger men. Prostate cancer
      prevalence is rising in HIV-infected men due to improved survival on
      antiretroviral therapies, yet little is known about racial differences in
      prostate cancer risk by HIV-infection status and age. METHODS: This is a
      prospective cohort study of prostate cancer risk in 2,800 HIV-infected and 
      uninfected men who have sex with men (MSM) aged 40-70 years (22% African
      American) who were enrolled in the multicenter AIDS cohort study from 1996 to
      2010. Poisson regression models were used to examine associations between race
      and HIV-infection status and prostate cancer risk among men aged 40-70, 40-55,
      and 56-70 years. RESULTS: Among men aged 40-70 years, incidence rates (IR) per
      100,000 person-years were 169 among all men and 276 among African American HIV
      infected men. Prostate cancer risk was similar by HIV-infection status (IRR 1.0,
      95% CI 0.55-1.82), but nearly threefold higher in African Americans compared to
      non-African Americans in adjusted models (IRRs 2.66 and 3.22, 95% CIs 1.36-5.18
      and 1.27-8.16 for all or HIV-infected men, respectively). Racial disparity in
      prostate cancer risk was greatest in African American men aged 40-55 years
      (adjusted IRR 3.31, 95% CI 1.19-9.22). Prostate cancer risk showed associations
      with family history of prostate cancer (p = 0.001), but not heavy smoking,
      androgen supplement use, or HIV-related factors. CONCLUSIONS: Among MSM, African
      American HIV-positive and HIV-negative men aged 40-55 years have threefold
      increased risk of young-onset prostate cancer compared to non-African American
      men, highlighting the need to make informed decisions about screening in this
      population.

PMID- 28451807
TI  - Increased risk of paclitaxel-induced peripheral neuropathy in patients using
      clopidogrel: a retrospective pilot study.
AB  - Paclitaxel-induced peripheral neuropathy (PIPN) is one of the serious adverse
      events associated with paclitaxel-based cancer treatments. A recent case study
      showed that the antiplatelet agent clopidogrel inhibits paclitaxel metabolism via
      cytochrome P450 (CYP) 2C8, resulting in severe PIPN. The aim of this study was to
      determine the impact of clopidogrel as a risk factor for the development of PIPN,
      using a retrospective cohort study. Data from paclitaxel-treated patients with or
      without clopidogrel and low-dose aspirin treatment were retrieved from medical
      charts. A total of 161 adult patients were included in this study: 135 were
      controls, 9 were clopidogrel-treated and 17 were aspirin-treated. The clopidogrel
      group had a greater proportion of males and a higher rate of comorbidities, such
      as diabetes mellitus and dyslipidemia, than the control group. However, patient
      characteristics were similar between the clopidogrel and aspirin groups. Severe
      PIPN was diagnosed in 3 (2.2%) and 2 (22.2%) patients in the control and
      clopidogrel groups, respectively (odds ratio: 12.0; p = 0.031). No patients in
      the aspirin group presented with severe neuropathy. These pilot data suggest that
      concomitant treatment with clopidogrel leads to a greater risk of PIPN. The
      avoidance of concomitant clopidogrel use may be effective in reducing clopidogrel
      associated PIPN.

PMID- 28451809
TI  - Microbial amensalism in Lactobacillus casei and Pseudomonas taetrolens mixed
      culture.
AB  - Pseudomonas taetrolens has recently been revealed as an effective microbial
      producer of lactobionic acid from carbohydrates contained in dairy byproducts. In
      terms of food industrial applications, the implementation of lactobionic acid
      biosynthesis coupled with the classic bacterial production of lactic acid appears
      an important goal. This research paper studies the simultaneous fermentation of
      residual cheese whey by P. taetrolens and Lactobacillus casei to co-produce
      lactic and lactobionic acids. Experimental data showed the importance of the
      interactions established between the two microorganisms. Changes in physiology,
      viability, growth, and productive capacity were tested experimentally.
      Lactobacillus was not seen to suffer any appreciable stress, but considerable
      variations were observed in the Pseudomonas behavior presumably owing to
      inhibitory lactic metabolites, interaction that can be classified as microbial
      amensalism. As to production, lactic acid remained without significant changes in
      mixed fermentations, whereas the production of lactobionic acid decreased sharply
      due to the competitive exclusion of Pseudomonas.

PMID- 28451810
TI  - Human Thiel-Embalmed Cadaveric Aortic Model with Perfusion for Endovascular
      Intervention Training and Medical Device Evaluation.
AB  - PURPOSE: The purpose of this investigation was to evaluate human Thiel-embalmed
      cadavers with the addition of extracorporeal driven ante-grade pulsatile flow in
      the aorta as a model for simulation training in interventional techniques and
      endovascular device testing. MATERIALS AND METHODS: Three human cadavers embalmed
      according to the method of Thiel were selected. Extracorporeal pulsatile ante
      grade flow of 2.5 L per min was delivered directly into the aorta of the cadavers
      via a surgically placed connection. During perfusion, aortic pressure and
      temperature were recorded and optimized for physiologically similar parameters.
      Pre- and post-procedure CT imaging was conducted to plan and follow up thoracic
      and abdominal endovascular aortic repair as it would be in a clinical scenario.
      Thoracic endovascular aortic repair (TEVAR) and endovascular abdominal repair
      (EVAR) procedures were conducted in simulation of a clinical case, under
      fluoroscopic guidance with a multidisciplinary team present. RESULTS: The Thiel
      cadaveric aortic perfusion model provided pulsatile ante-grade flow, with
      pressure and temperature, sufficient to conduct a realistic simulation of TEVAR
      and EVAR procedures. Fluoroscopic imaging provided guidance during the
      intervention. Pre- and post-procedure CT imaging facilitated planning and follow
      up evaluation of the procedure. CONCLUSION: The human Thiel-embalmed cadavers
      with the addition of extracorporeal flow within the aorta offer an anatomically
      appropriate, physiologically similar robust model to simulate aortic endovascular
      procedures, with potential applications in interventional radiology training and
      medical device testing as a pre-clinical model.

PMID- 28451808
TI  - Neuropathic Pain and Spinal Cord Injury: Phenotypes and Pharmacological
      Management.
AB  - Chronic neuropathic pain is a complicated condition after a spinal cord injury
      (SCI) that often has a lifelong and significant negative impact on life after the
      injury; therefore, improved pain management is considered a significant and unmet
      need. Neuropathic pain mechanisms are heterogeneous and the difficulty in
      determining their individual contribution to specific pain types may contribute
      to poor treatment outcomes in this population. Thus, identifying human
      neuropathic pain phenotypes based on pain symptoms, somatosensory changes, or
      cognitive and psychosocial factors that reflect specific spinal cord or brain
      mechanisms of neuropathic pain is an important goal. Once a pain phenotype can be
      reliably replicated, its relationship with biomarkers and clinical treatment
      outcomes can be analyzed, and thereby facilitate translational research and
      further the mechanistic understanding of individual differences in the pain
      experience and in clinical trial outcomes. The present article will discuss
      clinical aspects of SCI-related neuropathic pain, neuropathic pain phenotypes,
      pain mechanisms, potential biomarkers and pharmacological interventions, and
      progress regarding how defining neuropathic pain phenotypes may lead to more
      targeted treatments for these difficult pain conditions.

PMID- 28451811
TI  - Prospective Clinical and Pharmacological Evaluation of the Delcath System's
      Second-Generation (GEN2) Hemofiltration System in Patients Undergoing
      Percutaneous Hepatic Perfusion with Melphalan.
AB  - INTRODUCTION: Percutaneous hepatic perfusion (PHP) with melphalan is an effective
      treatment for patients with hepatic metastases, but associated with high rates of
      bone marrow depression. To reduce systemic toxicity, improvements have been made
      to the filtration system. In pre-clinical studies, the Delcath System's GEN2
      filter was superior to the first-generation filters. In this clinical study, we
      analysed the pharmacokinetics and toxicity of PHP using the new GEN2 filter.
      METHODS AND MATERIALS: Starting February 2014, two prospective phase II studies
      were initiated in patients with hepatic metastases from ocular melanoma or
      colorectal cancer. In 10 PHP procedures performed in the first 7 enrolled
      patients, blood samples were obtained to determine filter efficiency and systemic
      drug exposure. PHP was performed with melphalan 3 mg/kg with a maximum of 220 mg.
      Complications were assessed according to CTCAE v4.03. Response was assessed
      according to RECIST 1.1. RESULTS: Pharmacokinetic analysis of blood samples
      showed an overall filter efficiency of 86% (range 71.1-95.5%). The mean filter
      efficiency decreased from 95.4% 10 min after the start of melphalan infusion to
      77.5% at the end of the procedure (p = 0.051). Bone marrow depression was seen
      after up to 80.0% of 10 procedures, but was self-limiting and mostly
      asymptomatic. No hypotension-related complications or procedure-related mortality
      occurred. CONCLUSION: The GEN2 filter has a higher melphalan filter efficiency
      compared to the first-generation filters and a more consistent performance. PHP
      with the GEN2 filter appears to have an acceptable safety profile, but this needs
      further validation in larger studies.

PMID- 28451812
TI  - Debulking Atherectomy in the Peripheral Arteries: Is There a Role and What is the
      Evidence?
AB  - Traditional percutaneous balloon angioplasty and stent placement is based on
      mechanical plaque disruption and displacement within the arterial wall. On the
      contrary, transcatheter atherectomy achieves atherosclerotic plaque clearance by
      means of directional plaque excision or rotational plaque removal or laser plaque
      ablation. Debulking atherectomy may allow for a more uniform angioplasty result
      at lower pressures with consequently less vessel barotrauma and improved luminal
      gain, thereby decreasing the risk of plaque recoil and dissection that may
      require permanent metal stenting. It has been also argued that atherectomy may
      disrupt the calcium barrier and optimize drug transfer and delivery in case of
      drug-coated balloon applications. The authors discuss the various types of
      atherectomy devices available in clinical practice to date and critically
      appraise their mode of action as well as relevant published data in each case.
      Overall, amassed randomized and observational evidence indicates that
      percutaneous atherectomy of the femoropopliteal and infrapopliteal arteries may
      achieve high technical success rates and seems to lessen the frequency of bailout
      stenting, however, at the expense of increased risk of peri-procedural distal
      embolization. Long-term clinical outcomes reported to date do not support the
      superiority of percutaneous atherectomy over traditional balloon angioplasty and
      stent placement in terms of vessel patency or limb salvage. The combination of
      debulking atherectomy and drug-coated balloons has shown promise in early
      studies, especially in the treatment of more complex lesions. Unanswered
      questions and future perspectives of this continuously evolving endovascular
      technology as part of a broader treatment algorithm are discussed.

PMID- 28451813
TI  - Practice does not always make perfect: need for selection curricula in modern
      surgical training.
AB  - BACKGROUND: It is hypothesized that not all surgical trainees are able to reach
      technical competence despite ongoing practice. The objectives of the study were
      to assess a trainees' ability to reach technical competence by assessing learning
      patterns of the acquisition of surgical skills. Furthermore, it aims to determine
      whether individuals' learning patterns were consistent across a range of open and
      laparoscopic tasks of variable difficulty. METHODS: Sixty-five preclinical
      medical students participated in a training curriculum with standardized feedback
      over forty repetitions of the following laparoscopic and open technical tasks:
      peg transfer (PT), circle cutting (CC), intracorporeal knot tie (IKT), one-handed
      tie, and simulated laparotomy closure. Data mining techniques were used to
      analyze the prospectively collected data and stratify the students into four
      learning clusters. Performance was compared between groups, and learning curve
      characteristics unique to trainees who have difficulty reaching technical
      competence were quantified. RESULTS: Top performers (22-35%) and high performers
      (32-42%) reached proficiency in all tasks. Moderate performers (25-37%) reached
      proficiency for all open tasks but not all laparoscopic tasks. Low performers (8
      15%) failed to reach proficiency in four of five tasks including all laparoscopic
      tasks (PT 7.8%; CC 9.4%; IKT 15.6%). Participants in lower performance clusters
      demonstrated sustained performance disadvantage across tasks, with widely
      variable learning curves and no evidence of progression towards a plateau phase.
      CONCLUSIONS: Most students reached proficiency across a range of surgical tasks,
      but low-performing trainees failed to reach competence in laparoscopic tasks.
      With increasing use of laparoscopy in surgical practice, screening potential
      candidates to identify the lowest performers may be beneficial.

PMID- 28451814
TI  - The relationship between manometric subtype and outcomes of surgical treatment
      for patients with achalasia : Achalasia: manometric subtypes.
AB  - BACKGROUND: The Chicago Classification describes three distinct subtypes of
      achalasia and it appears to be a promising tool in predicting results of
      treatment with standard Heller Myotomy. The aim of this study is to analyze the
      outcomes of surgical treatment for achalasia using an extended Heller myotomy for
      each subtype and to identify additional parameters that may predict the success
      of therapy. METHODS: 72 consecutive patients with achalasia were evaluated at the
      University of Washington between 2008 and 2013. Symptom duration, patient age,
      and the degree of esophageal dilation (stage 1-3) as assessed by radiography were
      determined. We defined treatment failure as no improvement in symptoms and/or
      need for a second therapy within 1 year. Long-term follow-up data of 25 patients
      were available in the form of a survey evaluating overall satisfaction with the
      operation. RESULTS: The distribution of patients according to subtype included 13
      with type I, 54 with type II, and 5 with type III. All of the type I patients had
      some degree of esophageal dilation on radiography, whereas no dilation was found
      in the type III group. All patients underwent uneventful laparoscopic-extended
      Heller myotomy. Two patients were classified as failures, including one with type
      I and one with type II achalasia; however, further investigation revealed the
      cause of both failures to be the development of peptic stricture. Only one of the
      25 patients with long-term follow-up reported dissatisfaction with the treatment
      result and indicated persistent chest pain without dysphagia. CONCLUSIONS:
      Laparoscopic-extended Heller myotomy is a highly successful treatment for
      patients with achalasia and outcomes do not appear to vary significantly
      according to the manometric subtype. Failures may result from reflux in patients
      who develop esophagitis or stricture. Chest pain is not always responsive to
      esophagogastric myotomy despite relief of dysphagia.

PMID- 28451815
TI  - Laser acupuncture versus reflexology therapy in elderly with rheumatoid
      arthritis.
AB  - The purposes of this study are to determine and compare efficacy of laser
      acupuncture versus reflexology in elderly with rheumatoid arthritis. Thirty
      elderly patients with rheumatoid arthritis aged between 60 and 70 years were
      classified into two groups, 15 patients each. Group A received laser acupuncture
      therapy (904 nm, beam area of 1cm2, power 100 mW, power density 100 mW/cm2,
      energy dosage 4 J, energy density 4 J/cm2, irradiation time 40 s, and frequency
      100,000 Hz). The acupuncture points that were exposed to laser radiation are LR3,
      ST25, ST36, SI3, SI4, LI4, LI11, SP6, SP9, GB25, GB34, and HT7. While group B
      received reflexology therapy, both offered 12 sessions over 4 weeks. The changes
      in RAQoL, HAQ, IL-6, MDA, ATP, and ROM at wrist and ankle joints were measured at
      the beginning and end of treatment. There was significant decrease in RAQoL, HAQ,
      IL-6, and MDA pre/posttreatment for both groups (p < 0.05); significant increase
      in ATP pre/posttreatment for both groups (p < 0.05); significant increase in
      ankle dorsi-flexion, plantar-flexion, wrist flexion, extension, and ulnar
      deviation ROM pre/posttreatment in group A (p < 0.05); and significant increase
      in ankle dorsi-flexion and ankle plantar-flexion ROM pre/posttreatment in group B
      (p < 0.05). Comparison between both groups showed a statistical significant
      decrease in MDA and a statistical significant increase in ATP in group A than
      group B. Percent of changes in MDA was 41.82%? in group A versus 21.68%? in group
      B; changes in ATP was 226.97%? in group A versus 67.02%? in group B. Moreover,
      there was a statistical significant increase in ankle dorsi-flexion, ankle
      plantar-flexion, wrist flexion, wrist extension, and radial deviation in group A
      than group B. Laser therapy is associated with significant improvement in MDA and
      ATP greater than reflexology. In addition, it is associated with significant
      improvement in ankle dorsi-flexion, ankle plantar-flexion, wrist flexion, wrist
      extension, and radial deviation greater than reflexology in elderly patients with
      rheumatoid arthritis.

PMID- 28451816
TI  - In vitro biological outcome of laser application for modification or processing
      of titanium dental implants.
AB  - There are numerous functions for laser in modern implant dentistry including
      surface treatment, surface coating, and implant manufacturing. As laser
      application may potentially improve osseointegration of dental implants, we
      systematically reviewed the literature for in vitro biological responses to laser
      modified or processed titanium dental implants. The literature was searched in
      PubMed, ISI Web, and Scopus, using keywords "titanium dental implants," "laser,"
      "biocompatibility," and their synonyms. After screening the 136 references
      obtained, 28 articles met the inclusion criteria. We found that Nd:YAG laser was
      the most commonly used lasers in the treatment or processing of titanium dental
      implants. Most of the experiments used cell attachment and cell proliferation to
      investigate bioresponses of the implants. The most commonly used cells in these
      assays were osteoblast-like cells. Only one study was conducted in stem cells.
      These in vitro studies reported higher biocompatibility in laser-modified
      titanium implants. It seems that laser radiation plays a vital role in cell
      response to dental implants; however, it is necessary to accomplish more studies
      using different laser types and parameters on various cells to offer a more
      conclusive result.

PMID- 28451817
TI  - Morphometric analysis of high-intensity focused ultrasound-induced lipolysis on
      cadaveric abdominal and thigh skin.
AB  - Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices
      induce lipolysis by generating acoustic cavitation and coagulation necrosis in
      targeted tissues. We aimed to investigate the morphometric characteristics of
      immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two
      dimensional ultrasound images and histologic evaluation of cadaveric skin from
      the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were
      characterized by reconstruction of the fields using acoustic intensity
      measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were
      treated with a HIFU device for a single, two, and three pulses at the pulse
      energy of 130 J/cm2 and a penetration depth of 13 mm. Acoustic intensity
      measurement revealed characteristic focal zones of significant thermal injury at
      the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative
      thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon
      treatment with a single pulse of HIFU treatment. Two to three HIFU pulses
      generated larger and more remarkable ablative zones throughout subcutaneous fat
      layers. Finally, experimental treatment in a tumescent infiltration-like setting
      induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non
      tumescent settings. Although neither acoustic intensity measurement nor cadaveric
      tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we
      believe that our data will help guide further in vivo studies in investigating
      the therapeutic efficacy and safety of HIFU-induced lipolysis.

PMID- 28451818
TI  - A mass spectrometry-based forensic toolbox for imaging and detecting biological
      fluid evidence in finger marks and fingernail scrapings.
AB  - During a crime, biological material such as blood or vaginal fluid may become
      smeared on the fingers of the victim or suspect or trapped under their
      fingernails. The type of trapped fluid is extremely valuable forensic
      information. Furthermore, if either person touches an object at the crime scene
      with their 'contaminated' finger then a 'contaminated' finger mark may be
      deposited. Such marks have great value as they could identify not only who
      deposited the mark but also who they touched and which part of the body they
      touched. Here, we describe preliminary work towards a 'toolbox' of techniques
      based on mass spectrometry (MS) for the identification of biological fluid traces
      under fingernails or the imaging of them in finger marks. Liquid chromatography
      multidimensional MS was effective for the detection of protein biomarkers
      characteristic of vaginal fluid and blood trapped under fingernails, even after
      hands had been washed. In regard to examination of finger marks for the presence
      of biological fluids, the most practical implementation of any technique is to
      integrate it with, but after, routine crime scene finger mark enhancement has
      been applied. Here, we demonstrate the usage of matrix-assisted laser desorption
      ionization-time of flight-MS for the detection and mapping of proteins and
      peptides from body fluids in finger marks, including marks enhanced using
      aluminium-containing magnetic powder and then 'lifted' with adhesive tape.
      Hitherto, only small molecules have been detected in enhanced, lifted marks. In a
      novel development, aluminium in the enhancement powder assisted ionization of
      small molecules in finger marks to the extent that conventional matrix was not
      required for MS.

PMID- 28451819
TI  - Overexpression of miR529a confers enhanced resistance to oxidative stress in rice
      (Oryza sativa L.).
AB  - KEY MESSAGE: Overexpressing miR529a can enhance oxidative stress resistance by
      targeting OsSPL2 and OsSPL14 genes that can regulate the expression of their
      downstream SOD and POD related genes. MicroRNAs are involved in the regulation of
      plant developmental and physiological processes, and their expression can be
      altered when plants suffered environment stresses, including salt, oxidative,
      drought and Cadmium. The expression of microRNA529 (miR529) can be induced under
      oxidative stress. However, its biological function under abiotic stress responses
      is still unclear. In this study, miR529a was overexpressed to investigate the
      function of miR529a under oxidative stress in rice. Our results demonstrated that
      the expression of miR529a can be induced by exogenous H2O2, and overexpressing
      miR529a can increase plant tolerance to high level of H2O2, resulting in
      increased seed germination rate, root tip cell viability, reduced leaf rolling
      rate and chlorophyll retention. The expression of oxidative stress responsive
      genes and the activities of superoxide dismutase (SOD) and peroxidase (POD) were
      increased in miR529a overexpression plant, which could help to reduce redundant
      reactive oxygen species (ROS). Furthermore, only OsSPL2 and OsSPL14 were targeted
      by miR529a in rice seedlings, repressing their expression in miR529aOE plants
      could lead to strengthen plant tolerance to oxidation stress. Our study provided
      the evidence that overexpression of miR529a could strengthen oxidation
      resistance, and its target genes OsSPL2 and OsSPL14 were responsible for
      oxidative tolerance, implied the manipulation of miR529a and its target genes
      regulation on H2O2 related response genes could improve oxidative stress
      tolerance in rice.

PMID- 28451820
TI  - Analysis of the potato calcium-dependent protein kinase family and
      characterization of StCDPK7, a member induced upon infection with Phytophthora
      infestans.
AB  - KEY MESSAGE: We describe the potato CDPK family and place StCDPK7 as a player in
      potato response to Phytophthora infestans infection, identifying phenylalanine
      ammonia lyase as its specific phosphorylation target in vitro. Calcium-dependent
      protein kinases (CDPKs) decode calcium (Ca2+) signals and activate different
      signaling pathways involved in hormone signaling, plant growth, development, and
      both abiotic and biotic stress responses. In this study, we describe the potato
      CDPK/CRK multigene family; bioinformatic analysis allowed us to identify 20 new
      CDPK isoforms, three CDPK-related kinases (CRKs), and a CDPK-like kinase.
      Phylogenetic analysis indicated that 26 StCDPKs can be classified into four
      groups, whose members are predicted to undergo different acylation patterns and
      exhibited diverse expression levels in different tissues and in response to
      various stimuli. With the aim of characterizing those members that are
      particularly involved in plant-pathogen interaction, we focused on StCDPK7.
      Tissue expression profile revealed that StCDPK7 transcript levels are high in
      swollen stolons, roots, and mini tubers. Moreover, its expression is induced upon
      Phytophthora infestans infection in systemic leaves. Transient expression assays
      showed that StCDPK7 displays a cytosolic/nuclear localization in spite of having
      a predicted chloroplast transit peptide. The recombinant protein, StCDPK7:6xHis,
      is an active Ca2+-dependent protein kinase that can phosphorylate phenylalanine
      ammonia lyase, an enzyme involved in plant defense response. The analysis of the
      potato CDPK family provides the first step towards the identification of CDPK
      isoforms involved in biotic stress. StCDPK7 emerges as a relevant player that
      could be manipulated to deploy disease resistance in potato crops.

PMID- 28451822
TI  - A novel heterozygous deletion in the intron 8-exon 9 boundary of the glucokinase
      gene in a Chinese pedigree of GCK-MODY.

PMID- 28451821
TI  - Genome-wide analysis of autophagy-related genes in banana highlights MaATG8s in
      cell death and autophagy in immune response to Fusarium wilt.
AB  - KEY MESSAGE: MaATG8s play important roles in hypersensitive-like cell death and
      immune response, and autophagy is essential for disease resistance against Foc in
      banana. Autophagy is responsible for the degradation of damaged cytoplasmic
      constituents in the lysosomes or vacuoles. Although the effects of autophagy have
      been extensively revealed in model plants, the possible roles of autophagy
      related gene in banana remain unknown. In this study, 32 MaATGs were identified
      in the draft genome, and the profiles of several MaATGs in response to fungal
      pathogen Fusarium oxysporum f. sp. cubense (Foc) were also revealled. We found
      that seven MaATG8s were commonly regulated by Foc. Through transient expression
      in Nicotiana benthamiana leaves, we highlight the novel roles of MaATG8s in
      conferring hypersensitive-like cell death, and MaATG8s-mediated hypersensitive
      response-like cell death is dependent on autophagy. Notablly, autophagy inhibitor
      3-methyladenine (3-MA) treatment resulted in decreased disease resistance in
      response to Foc4, and the effect of 3-MA treatment could be rescued by exogenous
      salicylic acid, jasmonic acid and ethylene, indicating the involvement of
      autophagy-mediated plant hormones in banana resistance to Fusarium wilt. Taken
      together, this study may extend our understanding the putative role of MaATG8s in
      hypersensitive-like cell death and the essential role of autophagy in immune
      response against Foc in banana.

PMID- 28451823
TI  - Bilateral lower limb edema induced by rapid improvement of glycemic control with
      insulin therapy in a subject with poorly controlled type 2 diabetes.

PMID- 28451824
TI  - Heart Failure Guidelines on Pharmacotherapy.
AB  - Heart Failure (HF) is a serious emerging Public Health issue mainly in the high
      income countries. In the USA, more than 6 million adults are affected. Despite
      the latest advances in device and pharmacological therapeutics, it still carries
      a huge burden, partially reflected in the annual healthcare cost of approximately
      $30 billion (2012) and the 5 year mortality rate of 50%. In this article, we
      review the medications, proven to significantly reduce mortality and morbidity in
      HF patients with structural myocardial disease and past or current symptoms,
      based on the latest North American HF guidelines. We, finally, perform a brief
      comparison between the former recommendations and the published 2016 HF
      guidelines by European Society of Cardiology.

PMID- 28451825
TI  - Using PET for therapy monitoring in oncological clinical trials: challenges
      ahead.
AB  - Molecular imaging with PET has emerged as a powerful imaging tool in the clinical
      care of oncological patients. Assessing therapy response is a prime application
      of PET and so the integration of PET into multicentre trials can offer valuable
      scientific insights and shape future clinical practice. However, there are a
      number of logistic and methodological challenges that have to be dealt with.
      These range from availability and regulatory compliance of the PET
      radiopharmaceutical to availability of scan time for research purposes.
      Standardization of imaging and reconstruction protocols, quality control, image
      processing and analysis are of paramount importance. Strategies for harmonization
      of the final image and the quantification result are available and can be
      implemented within the scope of multicentre accreditation programmes. Data
      analysis can be performed either locally or by centralized review. Response
      assessment can be done visually or using more quantitative approaches, depending
      on the research question. Large-scale real-time centralized review can be
      achieved using web-based solutions. Specific challenges for the future are
      inclusion of PET/MRI scanners in multicentre trials and the incorporation of
      radiomic analyses. Inclusion of PET in multicentre trials is a necessity to
      guarantee the further development of PET for routine clinical care and may yield
      very valuable scientific insights.

PMID- 28451826
TI  - Is the information provided by amino acid PET radiopharmaceuticals clinically
      equivalent in gliomas?

PMID- 28451827
TI  - Accuracy of diagnostic imaging modalities for peripheral post-traumatic
      osteomyelitis - a systematic review of the recent literature.
AB  - AIMS: Post-traumatic osteomyelitis (PTO) is difficult to diagnose and there is no
      consensus on the best imaging strategy. The aim of this study is to present a
      systematic review of the recent literature on diagnostic imaging of PTO. METHODS:
      A literature search of the EMBASE and PubMed databases of the last 16 years (2000
      2016) was performed. Studies that evaluated the accuracy of magnetic resonance
      imaging (MRI), three-phase bone scintigraphy (TPBS), white blood cell (WBC) or
      antigranulocyte antibody (AGA) scintigraphy, fluorodeoxyglucose positron emission
      tomography (FDG-PET) and plain computed tomography (CT) in diagnosing PTO were
      considered for inclusion. The review was conducted using the PRISMA statement and
      QUADAS-2 criteria. RESULTS: The literature search identified 3358 original
      records, of which 10 articles could be included in this review. Four of these
      studies had a comparative design which made it possible to report the results of,
      in total, 17 patient series. WBC (or AGA) scintigraphy and FDG-PET exhibit good
      accuracy for diagnosing PTO (sensitivity ranged from 50-100%, specificity ranged
      from 40-97% versus 83-100% and 51%-100%, respectively). The accuracy of both
      modalities improved when a hybrid imaging technique (SPECT/CT & FDG-PET/CT) was
      performed. For FDG-PET/CT, sensitivity ranged between 86 and 94% and specificity
      between 76 and 100%. For WBC scintigraphy + SPECT/CT, this is 100% and 89-97%,
      respectively. CONCLUSIONS: Based on the best available evidence of the last 16
      years, both WBC (or AGA) scintigraphy combined with SPECT/CT or FDG-PET combined
      with CT have the best diagnostic accuracy for diagnosing peripheral PTO.

PMID- 28451828
TI  - Right persistent trigeminal artery variant (PTAV) and tiny left PTA associated
      with bilateral ophthalmic arteries arising from the cavernous segments of the
      internal carotid arteries.
AB  - Persistent trigeminal artery (PTA) and its variant (PTAV) are the most prevalent
      types of carotid-vertebrobasilar anastomosis, but bilateral anastomoses are
      exceedingly rare. We report a case of a right PTAV and tiny left lateral-type PTA
      from which the cerebellar artery (presumed anterior inferior cerebellar artery)
      arose. And also, bilateral ophthalmic arteries arose from the cavernous segments
      of the internal carotid arteries and entered the orbits via the superior orbital
      fissures. Selective cerebral angiography, especially 3-dimensional angiography,
      is superior to magnetic resonance (MR) angiography to identify rare variations of
      the cerebral arteries. Careful observation of MR angiographic source images is
      important for identifying unique arterial coursing.

PMID- 28451829
TI  - Human anatomic variations: common, external iliac, origin of the obturator,
      inferior epigastric and medial circumflex femoral arteries, and deep femoral
      artery course on the medial side of the femoral vessels.
AB  - Probably, the most variable anatomic pattern relates to the iliac arteries
      system. There are reported here multiple rare anatomic variants found in a single
      case, at CT evaluation: (a) the unilaterally present common trunk of origin of
      the obturator, inferior epigastric, and medial circumflex femoral arteries and
      (b) the medial insertion of the deep femoral artery (DFA) onto the femoral
      artery, which placed the DFA initially on the medial side of the femoral vein.
      Such rare, but possible, anatomic variations should recommend surgeons to plan
      the procedures on a case-by-case basis.

PMID- 28451830
TI  - Hemodialysis does not impact axitinib exposure: clinical case of a patient with
      metastatic renal cell carcinoma.
AB  - Axitinib is approved with indication in patients with advanced renal cell
      carcinoma (RCC). Due to the localization of this cancer, physicians sometimes
      have to deal with hemodialyzed patients. Data exploring hemodialysis (HD) impact
      on axitinib pharmacokinetic (PK) or safety are lacking. To date, no data have
      been published on that problematic. This is the first publication discussing the
      assessment of axitinib PK for a patient undergoing HD. Our results suggest that
      there is no influence of HD on axitinib blood concentration. Interestingly, the
      membranes used are common and represent around 90% of the membranes used in
      routine for HD. Our data are also reassuring both from activity and from safety
      perspectives. In that case, axitinib administered at a dose of 6 mg twice a day
      was well tolerated and allowed 12 months of disease control. These results are in
      line with previous publications discussing other anti-angiogenic tyrosine kinase
      inhibitors pharmacokinetics, safety and activity among patients with metastatic
      RCC undergoing hemodialysis.

PMID- 28451831
TI  - Enhancing the therapeutic range of a targeted small-molecule tubulysin conjugate
      for folate receptor-based cancer therapy.
AB  - PURPOSE: EC0305 represents a folate-tubulysin B construct capable of specifically
      eradicating folate receptor (FR)-positive subcutaneous tumors from mice (Leamon
      et al., Cancer Res 68:9839-9844, 8). Herein we report on the use of multiple
      polar carbohydrate segments (e.g. 1-amino-1-deoxy-glucitolyl-gamma-glutamate)
      placed in-between the folate and tubulysin B moieties of EC0305 creating a new
      conjugate, herein referred to as EC0531, with more desirable biological
      properties. METHODS: The synthesis of EC0531 and its tritium-labeled counterpart
      are described. EC0531's affinity for FR binding and specific cytotoxic activity
      was assessed using standard in vitro assays. Human tumor xenografts were used to
      directly compare EC0305 and EC0531's antitumor activity. Finally, bile duct
      cannulated, female Sprague-Dawley rats were used to compare hepatobiliary
      clearance of these two targeted chemotherapeutic agents. RESULTS: EC0531 tightly
      binds to the FR with an affinity about half that of folic acid. It was found to
      specifically inhibit the growth of FR+ cells (IC50 of ~2 nM) in a dose-dependent
      manner. Using 3H-labeled compounds, more than a 12-fold higher amount of
      tubulysin was measured in a FR + human tumor xenograft compared to the
      unconjugated drug, a finding that explains, in part, why EC0531 displays curative
      activity, whereas the unconjugated tubulysin agent is essentially inactive.
      EC0531 was found to produce greater FR-specific anti-tumor activity at lower dose
      levels than EC0305; furthermore, EC0531's maximum tolerated dose level was
      significantly higher than that of EC0305, likely because EC0531's
      saccharopeptidic-based spacer allows for ~sixfold reduction in hepatic clearance.
      CONCLUSIONS: These data provide additional evidence that the therapeutic range of
      targeted small-molecule drug conjugates can be favorably increased using
      molecular spacers constructed with 1-amino-1-deoxy-glucitolyl-gamma-glutamate
      residues.

PMID- 28451832
TI  - In vitro and in vivo assessments of two novel hydrazide compounds against breast
      cancer as well as mammary tumor cells.
AB  - PURPOSE: The hydrazide backbone is a well-known structural core system found in a
      broad range of biologically activated compounds. Among which, the compounds with
      anticancer activity have been cited in a number of studies. With this object in
      mind, we focused on the in vitro and in vivo anticancer potential of two novel
      hydrazide derivatives bearing furan or thiophen substituents (compounds 1 and 2).
      METHODS: The cytotoxic property was evaluated using MTT assay against MCF-7 human
      breast adenocarcinoma cell line, while the in vivo antitumor activity was
      investigated in BALB/c mice bearing 4T1 mammary carcinoma cells. Flow cytometry
      was used for cell cycle analysis, and detection of apoptosis was examined by
      Annexin-V-FLUOS/PI assay. Protein expression of Bax, Bcl-2 and procaspase-3 was
      estimated by Western blotting. RESULTS: Compounds 1 and 2 were found to be
      cytotoxic towards breast cancer cells presenting IC50 values of 0.7 and 0.18 uM,
      respectively, and selectivity over normal fibroblast cells. Our findings further
      indicated that 2 * IC50 concentrations of both compounds induce early stage
      apoptosis and increase percentage of sub-G1 population in MCF-7 cells at 48 h. An
      elevation in Bax/Bcl-2 ratio and caspase-3 cleavage suggested that apoptosis
      induced by the two compounds is through a caspase- and mitochondrial-dependent
      pathway. In the in vivo study, compounds 1 and 2 at doses of 10 and 1 mg/Kg/day,
      respectively, significantly hindered the growth of tumor after 3 weeks of i.p.
      administration, when compared to vehicle-treated mice. CONCLUSION: Collectively,
      the great potential exhibited by compound 2 could make it a promising
      chemotherapeutic candidate for human cancers, especially for breast cancer.

PMID- 28451833
TI  - Phase 1b study of galunisertib in combination with gemcitabine in Japanese
      patients with metastatic or locally advanced pancreatic cancer.
AB  - PURPOSE: Transforming growth factor-beta inhibitors may enhance the antitumor
      activity of gemcitabine with acceptable safety and tolerability. This open-label,
      multicenter, non-randomized phase 1b study assessed the safety/tolerability,
      pharmacokinetics, and tumor response of galunisertib plus gemcitabine in Japanese
      patients with advanced or metastatic pancreatic cancer. METHODS: During each 28
      day cycle, galunisertib 150 mg was administered orally twice daily (300 mg/day)
      for 14 days, followed by 14 days of rest. Gemcitabine 1000 mg/m2 was
      intravenously given on Days 8, 15, and 22. Safety was assessed by the incidence
      of dose-limiting toxicities (DLTs) in the first cycle and treatment-emergent
      adverse events (TEAEs). Efficacy was assessed by antitumor activity and changes
      in carbohydrate antigen 19-9 (CA19-9). RESULTS: No DLTs were reported. All 7
      enrolled patients had >=1 TEAE, of which the most common included anorexia,
      decreased neutrophil count, and decreased white blood cell count. Grade >=3 TEAEs
      were observed in 6 patients; 4 patients had Grade >=3 TEAEs (decreased
      neutrophil, white blood cell, and lymphocyte count; hypophosphatemia) considered
      possibly related to study drug(s). The pharmacokinetic profile of galunisertib in
      combination with gemcitabine was similar to that previously observed for
      galunisertib alone. The clinical response [complete response (CR), partial
      response (PR), or stable disease] rate was 42.9%, and the median progression-free
      survival was 64 days; no CR/PR were achieved. CONCLUSION: Galunisertib plus
      gemcitabine had an acceptable safety/tolerability profile with evidence of
      efficacy in Japanese patients with advanced or metastatic pancreatic cancer.

PMID- 28451834
TI  - Penetration rate of the placement of a drug-eluting stent for the treatment of
      superficial femoral artery lesions in Japan.
AB  - Stent placement for treating superficial femoral artery (SFA) lesions has been
      approved. The Zilver PTX stent, a drug-eluting stent (DES) for treating SFA
      lesions, has been available in Japan since 2012. However, the penetration rate of
      this DES has not yet been reported. This prospective multicenter registry study
      enrolled 314 patients (354 limbs) to be treated by stent placement in 2014
      (UMIN000011551). The primary endpoint was the measurement of the penetration rate
      of the DES. The secondary endpoints were measuring the freedom from restenosis,
      freedom from target lesion revascularization (TLR), freedom from major adverse
      limb event (MALE), and the survival rate at 12 months postoperatively. Female
      patients comprised 28% participants. The mean age was 73.1 +/- 9.2 years. A total
      of 56% patients had diabetes mellitus (DM), 36% patients were receiving
      hemodialysis, and 30% used cilostazol at baseline. The mean lesion length was 156
      +/- 101 mm, and the percentage of TASC II C/D lesions was 58%. Critical limb
      ischemia (CLI) was observed in 32% limbs. The penetration rates of the Zilver PTX
      stent were only 8%. The primary patency rate was similar between DES and bare
      metal stents (BMS) at 12 months postoperatively (77 vs. 84%, p = 0.52). In this
      study, the rates of freedom from restenosis, freedom from TLR, freedom from MALE,
      and the survival rate at 12 months postoperatively were 83, 86, 85, and 89%,
      respectively. The penetration rate of a first-generation DES placement for
      treating SFA lesions is low in Japan. On the other hand, BMS is well utilized and
      its primary patency is acceptable.

PMID- 28451835
TI  - Significance of sequential cardiac rehabilitation program through inter-hospital
      cooperation between acute care and rehabilitation hospitals in elderly patients
      after cardiac surgery in Japan.
AB  - This study is to evaluate the impact of cooperation between acute care hospital
      and rehabilitation hospital on physical function, exercise tolerance, activities
      of daily living (ADL), health-related quality of life (HR-QOL), and psychological
      function in heart disease patients undergoing cardiac rehabilitation. Among
      patients undergoing concurrent medical treatment and cardiac rehabilitation
      starting early in acute care hospitalization, we selected 30 patients who
      required continued cardiac rehabilitation in rehabilitation hospitals as
      subjects. At the time of admission and discharge from the rehabilitation
      hospital, we measured and compared physical function [grip strength, knee
      extension strength, and the short physical performance battery (SPPB)], ADL
      ability using the Functional Independence Measure (FIM), exercise tolerance [six
      minute walking distance (6MD)], and psychological functions such as the MOS 36
      Item Short-Form Health Survey (SF-36). The average age of the subjects was 76.8
      years and 60% were women. In 70% of cases, musculoskeletal causes were the
      reasons for continued cardiac rehabilitation in a rehabilitation hospital. In
      evaluations before and after hospitalization, significant improvements were
      observed in knee extension strength and the results of the SPPB (p < 0.01), FIM,
      and 6MD (p < 0.01). In SF-36, significant improvements were observed in physical
      function, role functioning, vitality, and emotional functioning (p < 0.05, p <
      0.01). With intensive cardiac rehabilitation in rehabilitation hospitals,
      physical function, ADL, exercise tolerance, and HR-QOL improved significantly. As
      the severity and prevalence of heart disease are expected to increase in
      association with multiple disabilities and aging, the importance of cooperation
      between acute care hospitals and rehabilitation hospitals will increase;
      therefore, cardiac rehabilitation should be the basis for such cooperation.

PMID- 28451836
TI  - Modeling Beliefs, Attitudes, and Intentions of Condom Use Among Secondary School
      Students in Kenya.
AB  - As in other parts of sub-Saharan Africa, youth in Kenya report low rates of
      condom use. Although several studies have explored reasons for the low condom use
      among Kenyan youth, not many have established linkages between lack of use and
      normative beliefs and attitudes around condoms. Using the Theory of Planned
      Behavior (TPB), this article examined whether beliefs and attitudes around
      condoms influenced intentions and actual condom use. Data for the study were
      restricted to 1453 sexually active youth during the last school break. Path
      analysis was used to examine the relationship between the TPB constructs and
      condom use among Kenyan youth. Results indicated a direct relationship between
      attitudes and condom use for male respondents and an indirect relationship
      between these two variables for females. Both males and females who expressed
      greater intentions to use condoms were significantly more likely to report they
      used condoms consistently. Also, male and female youth with higher perceived
      behavioral control were significantly more likely to have used condoms
      consistently. Males with friends who used condoms were significantly more likely
      to use condoms consistently. The findings suggest the importance of examining
      young people's attitudes toward condoms-in particular, those deeply rooted in
      misconceptions that serve to discourage safer sexual behaviors.

PMID- 28451837
TI  - High-level productivity of alpha,omega-dodecanedioic acid with a newly isolated
      Candida viswanathii strain.
AB  - alpha,omega-Dicarboxylic acids (DC) are versatile chemical intermediates with
      different chain lengths, which are well-known as polymer building block. In this
      work, a new strain with high productivity of DC was isolated from oil
      contaminated soil. Based on the morphology and phylogenetic analyses of the
      internal transcribed spacer sequences, it was characterized as Candida
      viswanathii. It was found that the contribution of carbon flux to the cell growth
      and DC production from n-dodecane could be regulated by the sucrose and yeast
      extract concentrations in the medium, and besides the broth pH, a suitable
      proportioning of sucrose and yeast extract was the key to achieve the optimal
      transition from cell growth phase to DC production phase. By optimizing culture
      conditions in a 7.5-L bioreactor, a higher DC productivity of 1.59 g.L-1 h-1 with
      a corresponding concentration of 181.6 g/L was obtained. After the purification
      of DC from the culture, the results from gas chromatography-mass spectrometry,
      infrared spectroscopy and 1H-NMR showed that alpha,omega-dodecanedioic acid
      (DC12) was the major product of C. viswanathii ipe-1 using pure n-dodecane as
      substrate. For the first time, we reported that a high productivity of DC12 could
      be produced by C. viswanathii.

PMID- 28451838
TI  - Improved cider fermentation performance and quality with newly generated
      Saccharomyces cerevisiae * Saccharomyces eubayanus hybrids.
AB  - Yeast cryotolerance may be advantageous for cider making, where low temperatures
      are usually employed. Here, we crossed the cryotolerant S. eubayanus with a S.
      cerevisiae wine strain and assessed the suitability of the hybrids for low
      temperature cider fermentation. All strains fermented the juice to 5% ABV, but at
      different rates; hybrid strains outperformed S. cerevisiae, which was sensitive
      to low temperatures. The best hybrid fermented similarly to S. eubayanus. S.
      eubayanus produced sulphurous off flavours which masked a high concentration of
      fruity ester notes. This phenotype was absent in the hybrid strains, resulting in
      distinctly fruitier ciders. Aroma was assessed by an independent consumer panel,
      which rated the hybrid ciders as identical to the wine strain cider. Both were
      significantly more pleasant than the S. eubayanus cider. Interspecific
      hybridization can apparently be used effectively to improve low-temperature
      fermentation performance without compromising product quality.

PMID- 28451840
TI  - Clinical characteristics associated with bradycardia and asystole in patients
      with syncope undergoing long-term electrocardiographic monitoring with
      implantable loop recorder.
AB  - BACKGROUND: The aim of this retrospective single center cohort study was to
      assess the occurrence of bradycardia during implantable loop recorder (ILR)
      monitoring in patients with unexplained syncope and negative conventional testing
      and to identify clinical predictors of bradycardia and pacemaker implantation.
      METHODS: An ILR was implanted in 112 patients (31 men, 81 women, mean age 64 +/
      13 years) with syncope which was not explained after conventional diagnostic work
      up. Clinical variables were compared between patients with and without pacemaker
      implantation. RESULTS: A diagnosis was made in 67 patients (60%), including non
      arrhythmic (vasodepressor) syncope (27 patients), sinus bradycardia or asystole
      (23 patients), atrioventricular (AV) block (14 patients) and bradycardic atrial
      fibrillation (3 patients). The mean time to diagnosis was 233 +/- 282 days. A
      pacemaker was implanted in 40 patients (36%). Male gender, age above 65 years,
      hypertension, presence of structural heart disease, absence of prodromal
      symptoms, trauma secondary to syncope, asymptomatic sinus bradycardia and first
      degree AV block were clinical predictors of pacemaker implantation in univariate
      analysis. Of the independent predictive factors three remained significant in
      multivariate analysis: absence of prodromal symptoms before the loss of
      consciousness (odds ratio OR 3.38, p = 0.01, 95% confidence interval CI 1.24
      9.20), male gender (OR 3.22, p = 0.01, 95% CI 1.26-8.20) and age >65 years (OR
      2.94, p = 0.02, 95% CI 1.14-8.33). CONCLUSIONS: In patients undergoing ILR
      implantation bradycardia is a frequent finding despite the negative conventional
      diagnostic testing. Absence of prodromal symptoms, male gender and age >65 years
      are risk factors for bradycardia and pacemaker implantation.

PMID- 28451841
TI  - Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental
      Subarachnoid Hemorrhage.
AB  - Roflumilast, a selective inhibitor for PDE4, is approved by FDA as an anti
      inflammation drug for treatment of chronic obstructive pulmonary disease (COPD).
      This study investigates the effects of roflumilast on cerebral inflammation in
      the rat SAH model. Here, we show that subcutaneous administration of roflumilast
      (3 mg/kg) significantly improved the neurological deficits. Measurement of evans
      blue extravasation and brain water content revealed a significant reduction of
      blood-brain barrier permeability and brain edema. Importantly, roflumilast
      treatment remarkably decreased levels of IL-1beta, IL-6, and TNF-alpha and the
      number of apoptotic neurons in the brain after SAH. These results indicate that
      roflumilast is effective in treating cerebral inflammation following SAH.

PMID- 28451842
TI  - Anterior cervical discectomy without fusion for a symptomatic cervical disk
      herniation.
AB  - BACKGROUND: Cervical radiculopathy is characterized by dysfunction of the nerve
      root usually caused by a cervical disk herniation. The most important symptom is
      pain, radiating from the neck to the arm. When conservative treatment fails,
      surgical treatment is indicated to relieve symptoms. During the last decades,
      multiple fusion techniques have been developed, although without clinical
      evidence for added value of fusion over non-fusion. METHODS: The surgical
      procedure of anterior cervical discectomy without fusion is performed step by
      step, leading to removal of the entire intervertebral disk. CONCLUSION: Anterior
      cervical discectomy without fusion is a safe and effective treatment for cervical
      disk herniation.

PMID- 28451843
TI  - Attachment and Mental Help-Seeking in the Perinatal Period: The Role of Stigma.
AB  - This study aimed at (1) examining how women's attachment representations
      influence their intentions to seek formal help for their emotional problems,
      either directly or by affecting attitudes towards professional help-seeking
      (stigma and psychological openness), and (2) examining whether these effects are
      moderated by the presence of clinically significant psychopathological symptoms.
      A cross-sectional online survey including 226 women during the perinatal period
      was conducted. Results showed that, when clinically significant
      psychopathological symptoms were present, women's more insecure attachment
      representations were associated with lower intentions to seek professional help,
      and this influence occurred throughout a decrease in women's indifference to
      stigma associated with mental healthcare. These results support both the intra
      and interpersonal nature of the help-seeking process, and highlight the
      importance of implementing stigma reduction strategies (e.g., awareness
      campaigns, health professional's non-judgmental questioning of emotional
      difficulties), particularly in women with clinically significant
      psychopathological symptoms.

PMID- 28451844
TI  - Predictors for recurrent/persistent high-grade intraepithelial lesions and
      cervical stenosis after therapeutic conization: a retrospective analysis of 522
      cases.
AB  - OBJECTIVE: The objective of the study is to identify the risk factors associated
      with recurrent/persistent disease and cervical stenosis after conization.
      METHODS: Five hundred twenty-two (522) cases of high-grade intraepithelial
      lesions treated by conization were retrospectively reviewed. Risk factors
      associated with recurrent/persistent disease were analyzed by univariate and
      multivariate analysis using a Cox hazard regression model. Factors that could
      potentially affect the risk of cervical stenosis were examined by univariate and
      by multivariate analysis using the chi 2 test and logistic regression,
      respectively. RESULTS: Recurrent/persistent diseases and cervical stenosis
      occurred in 4.8% and 5.4% of the patients, respectively. Age >=46 years [hazard
      ratio (HR) 3.6, 95% CI 1.36-10.3, p = 0.0092] and surgical margin involvement (HR
      13.44, 95% CI 5.07-46.37, p < 0.001) were independent predictors for
      recurrent/persistent diseases. Age >=46 years [odds ratio (OR) 4.27, 95% CI 1.88
      10.07, p < 0.001] and shortened interval after childbirth to conization (within
      12 months) (OR 5.42, 95% CI 1.42-17.41, p = 0.016) were independent risk factors
      for cervical stenosis. CONCLUSION: Elderly patients (aged >=46 years) are at high
      risk of recurrence and cervical stenosis, which may lead to unsatisfactory follow
      up. Subsequent hysterectomy is beneficial to patients aged 46 or older with
      surgical margin involvement. Clinicians should recognize the possibility of
      cervical stenosis after conization during the breastfeeding period, leading to
      secondary infertility or hematometra.

PMID- 28451845
TI  - Reflux esophagitis and its role in the pathogenesis of Barrett's metaplasia.
AB  - Reflux esophagitis damages the squamous epithelium that normally lines the
      esophagus, and promotes replacement of the damaged squamous lining by the
      intestinal metaplasia of Barrett's esophagus, the precursor of esophageal
      adenocarcinoma. Therefore, to prevent the development of Barrett's metaplasia and
      esophageal adenocarcinoma, the pathogenesis of reflux esophagitis must be
      understood. We have reported that reflux esophagitis, both in a rat model and in
      humans, develops as a cytokine-mediated inflammatory injury (i.e., cytokine
      sizzle), not as a caustic chemical injury (i.e., acid burn), as traditionally has
      been assumed. Moreover, reflux induces activation of hypoxia inducible factor
      (HIF)-2alpha, which enhances the transcriptional activity of nuclear factor kappa
      light-chain-enhancer of activated B cells (NF-kappaB) causing increases in pro
      inflammatory cytokines and in migration of T lymphocytes, an underlying molecular
      mechanism for this cytokine-mediated injury. In some individuals, reflux
      esophagitis heals with Barrett's metaplasia. A number of possibilities exist for
      the origin of the progenitor cells that give rise to this intestinal metaplasia
      including those of the esophagus, the proximal stomach, or the bone marrow.
      However, intestinal cells are not normally found in the esophagus, the stomach,
      or the bone marrow. Thus, the development of Barrett's intestinal metaplasia must
      involve some molecular reprogramming of key developmental transcription factors
      within the progenitor cell, a process termed transcommitment, which may be
      initiated by the noxious components of the gastric refluxate. This review will
      highlight recent studies on the pathogenesis of reflux esophagitis and on reflux
      related molecular reprogramming of esophageal squamous epithelial cells in the
      pathogenesis of Barrett's metaplasia.

PMID- 28451846
TI  - Conservation and diversity of the regulators of cellulolytic enzyme genes in
      Ascomycete fungi.
AB  - In the past decade, various transcriptional activators of cellulolytic enzyme
      genes have been identified in Ascomycete fungi. The regulatory system of
      cellulolytic enzymes is not only partially conserved, but also significantly
      diverse. For example, Trichoderma reesei has a system distinct from those of
      Aspergillus and Neurospora crassa-the former utilizes Xyr1 (the Aspergillus XlnR
      ortholog) as the major regulator of cellulolytic enzyme genes, while the latter
      uses CLR-2/ClrB/ManR orthologs. XlnR/Xyr1 and CLR-2/ClrB/ManR are evolutionarily
      distant from each other. Regulatory mechanisms that are controlled by CLR-2,
      ClrB, and ManR are also significantly different, although they are orthologous
      factors. Expression of clr-2 requires the activation of another transcription
      factor, CLR-1, by cellobiose, while CLR-2 is constitutively active for
      transactivation. By contrast, ClrB activation requires cellobiose. While ClrB
      mainly regulates cellulolytic genes, ManR is essential for the activation of not
      only cellulolytic but also mannanolytic enzyme genes. In this review, we
      summarize XlnR/Xyr1- and CLR-2/ClrB/ManR-dependent regulation in N. crassa, A.
      nidulans, A. oryzae, and T. reesei and emphasize the conservation and diversity
      of the regulatory systems for cellulolytic enzyme genes in these Ascomycete
      fungi. In addition, we discuss the role of McmA, another transcription factor
      that plays an important role in recruiting ClrB to the promoters in A. nidulans.

PMID- 28451847
TI  - Ribosome profiling the cell cycle: lessons and challenges.
AB  - Understanding the causes and consequences of dynamic changes in the abundance and
      activity of cellular components during cell division is what most cell cycle
      studies are about. Here we focus on control of gene expression in the cell cycle
      at the level of translation. The advent of deep sequencing methodologies led to
      technologies that quantify the levels of all mRNAs that are bound by ribosomes
      and engaged in translation in the cell (Ingolia et al. Science 324:218-223,
      2009). This approach has been applied recently to synchronous cell populations to
      find transcripts under translational control at different cell cycle phases
      (Blank et al. EMBO J 36:487-502, 2017; Stumpf et al. Mol Cell 52:574-582, 2013;
      Tanenbaum et al. Elife 4:e07957, 2015). These studies revealed new biology, but
      they also have limitations, pointing to challenges that need to be addressed in
      the future.

PMID- 28451848
TI  - Does Potassium Deficiency Contribute to Hypertension in Children and Adolescents?
AB  - The increasing prevalence of cardiovascular risk factors in children and
      adolescents has been largely, but not entirely, related to the childhood obesity
      epidemic. Among the noted risk factors detectable in children is elevated blood
      pressure. Emerging findings indicate that in addition to overweight and obesity,
      sodium intake is associated with elevated blood pressure in youth. Moreover,
      dietary sodium intake is quite high and well above recommended levels throughout
      childhood. In adults, the relationship of sodium consumption with hypertension is
      well established, and there is evidence from both population and clinical studies
      that potassium intake is also associated with blood pressure. Higher potassium
      intake is associated with lower blood pressure; and potassium deficit leads to an
      increase in blood pressure. Findings on relationships of potassium intake with
      blood pressure in childhood are sparse. There are some reports that provide
      evidence that a dietary pattern that includes potassium-rich foods is associated
      with lower blood pressure and may also lower blood pressure in adolescents with
      elevated blood pressure. Considering the secular changes in dietary patterns
      throughout childhood, it is prudent to encourage a diet for children that is high
      in potassium-rich foods.

PMID- 28451849
TI  - Role of Carotid Body in Intermittent Hypoxia-Related Hypertension.
AB  - Obstructive sleep apnea (OSA), a common breathing disorder, is recognized as an
      independent risk factor for systemic hypertension. Among the alterations induced
      by OSA, the chronic intermittent hypoxia (CIH) is considered the main factor for
      the hypertension. Exposure of rodents to CIH is the gold-standard method to study
      the mechanisms involved in the cardiovascular alterations induced by OSA.
      Although it is well known that CIH produces hypertension, the underlying
      mechanisms are not totally elucidated. It is likely that the CIH-induced systemic
      oxidative stress and inflammation may elicit endothelial dysfunction and increase
      the arterial blood pressure. In addition, OSA patients and animals exposed to CIH
      show sympathetic hyperactivity and potentiated cardiorespiratory responses to
      acute hypoxia, suggesting that CIH enhances the peripheral hypoxic chemoreflex.
      Recent experimental evidences support the proposal that CIH selectively enhances
      carotid body (CB) chemosensory reactivity to oxygen, which in turn increases
      sympathetic outflow leading to neurogenic hypertension. In this review, we will
      discuss the supporting evidence for a critical role of the CB in the generation
      and maintenance of the hypertension induced by CIH, also, the contribution of
      oxidative stress to enhance CB chemosensory drive and the activation of
      sympathetic-related centers in the brain.

PMID- 28451850
TI  - Drug-Induced Hypertension: Focus on Mechanisms and Management.
AB  - PURPOSE OF REVIEW: This review is intended to briefly describe the primary
      mechanistic pathways by which several common drugs can increase blood pressure.
      We also propose potential management strategies based on the underlying
      mechanisms responsible for the blood pressure elevation. RECENT FINDINGS: As
      hypertension is a significant risk factor for cardiovascular events, healthcare
      providers must evaluate patients' concomitant medications that may contribute to
      elevations in blood pressure. The presence of these medications, if not properly
      addressed, can lead to consequences such as an inadvertent diagnosis of
      hypertension, as well as the potential need for unnecessary intensification of
      antihypertensive regimens in those already treated. Blood pressure elevation is
      an unfortunate by-product of multiple medications. The substances discussed in
      this review can elicit significant and persistent elevations in blood pressure,
      and health care providers must first evaluate whether the drug is necessary. If
      one exists, it is best to select a similar agent with lower risk of increasing
      blood pressure; if unavoidable, then clinicians should select an appropriate
      management strategy to compensate for the rise in blood pressure.

PMID- 28451851
TI  - Obesity-Associated Hypertension: the Upcoming Phenotype in African-American
      Women.
AB  - PURPOSE OF REVIEW: The present obesity epidemic particularly affects African
      American women. Whether the obesity epidemic will alter the hypertension
      phenotype in African-American women is entertained. RECENT FINDINGS: The
      prevalence of morbid obesity is steadily increasing in African-American women,
      who are prone to developing hypertension (HTN) even in the absence of obesity.
      The obesity-associated hypertension phenotype is characterized by marked
      sympathetic nervous system activation and resistance/refractoriness to
      antihypertensive therapy. Weight loss achieved through lifestyle interventions
      and pharmacotherapy has a modest and rarely sustained antihypertensive effect. In
      contrast, bariatric surgery has a sustained antihypertensive effect, as evidenced
      by normalization of hypertension or lessening of antihypertensive therapy. The
      prevalence of HTN and its obesity-associated phenotype is likely to increase in
      African-American women over the next decades. Obese African-American women may be
      increasingly referred for bariatric surgery when hypertension remains
      uncontrolled despite lifestyle interventions and pharmacological therapy for
      weight loss and blood pressure (BP) control.

PMID- 28451852
TI  - Mineralocorticoid Receptor Blockade in End-Stage Renal Disease.
AB  - PURPOSE OF REVIEW: The purpose of this study was to summarize recent findings
      about cardiovascular benefits and safety of aldosterone blockade in patients with
      end-stage renal disease (ESRD). RECENT FINDINGS: It is now well recognized that
      aldosterone's deleterious cardiovascular impact is not limited to its pressor
      effect arising from an increase in sodium reabsorption in the kidneys.
      Aldosterone has also been shown to increase blood pressure by a direct activation
      of the sympathetic nervous system, to cause endothelial and vascular smooth
      muscle cell dysfunction, myocardial remodeling and fibrosis, and to have pro
      arrhythmogenic actions in the heart. These unconventional extra-renal effects of
      aldosterone make its blockade feasible and potentially beneficial for patients
      with ESRD. Accumulating data support the idea that aldosterone antagonism leads
      to a better blood pressure control, reduction in left ventricular (LV) mass,
      improved LV function, and reduced all-cause and cardiovascular mortality in ESRD
      patients. Reassuringly, rates of major adverse events, especially, significant
      hyperkalemia-the most feared adverse consequence-were low with careful patient
      selection and monitoring.

PMID- 28451853
TI  - Management of Hypertension in Patients with Chronic Kidney Disease.
AB  - Hypertension is the leading factor in the global burden of disease. It is the
      predominant modifiable risk factor for stroke, heart disease, and kidney failure.
      Chronic kidney disease (CKD) is both a common cause and sequel of uncontrolled
      hypertension. The pathophysiology of CKD-associated hypertension is complex and
      multi-factorial. This paper reviews the key pathogenic mechanisms of CKD
      associated hypertension, the importance of standardized blood pressure (BP)
      measurement in establishing the diagnosis and management plus the significance of
      ambulatory BP monitoring for assessment of diurnal BP variation commonly seen in
      CKD. The optimal BP target in CKD remains a matter of discussion despite recent
      clinical trials. Medical therapy can be difficult and challenging. In addition to
      lifestyle modification and dietary salt restriction, treatment may need to be
      individualized based on co-morbidities. Combination of antihypertensive drugs,
      including appropriate diuretic choice and dose, is of great significance in
      hypertension management in CKD.

PMID- 28451855
TI  - Performance and carcass characteristics of lambs fed diets with increasing levels
      of Mimosa tenuiflora (Willd.) hay replacing Buffel grass hay.
AB  - This study evaluated the performance and carcass characteristics of lambs fed
      diets with increasing levels of Mimosa tenuiflora (Willd.) hay replacing Buffel
      grass (Cenchrus ciliaris). Twenty-eight Santa Ines male lambs with an average
      body weight (BW) of 20.3 +/- 1.49 kg(mean +/- SD) were allocated in individual
      stalls and distributed in a completely random design with four treatments (0, 20,
      40, and 60 g/100 g total DM M. tenuiflora hay replacing Buffel grass hay in diet)
      with seven replications. M. tenuiflora hay at the level of 20% dry matter (DM)
      total replacing Buffel grass hay increased final weight (P = 0.006), total weight
      gain (P < 0.001), average daily weight gain (ADWG; P < 0.001), DM intake (P <
      0.001), and feed efficiency (P < 0.001). Intake of crude protein, NDFap, ADFap,
      ash, ether extract, total and non-fibrous carbohydrates, and total digestible
      nutrients presented a positive quadratic effect with M. tenuiflora hay replacing
      Buffel grass hay and 40 g/100 g total DM level presented greater intake. There
      were positive quadratic effects by M. tenuiflora hay inclusion at 20 g/100 g
      total DM level on slaughtering weight (P = 0.005), hot carcass weight (P =
      0.002), cold carcass weight (P = 0.002), empty body weight (P = 0.001), hot
      carcass yield (P = 0.002), cold carcass yield (P = 0.003), and increase linear on
      biological yield (P = 0.003). There was no influence on cooling weight loss (P =
      0.284). M. tenuiflora hay may be included in lamb diets at amounts up to 20 g/100
      g total DM substitution of Buffel grass hay because increase in the nutrients
      intake, growth performance, and carcass characteristics.

PMID- 28451854
TI  - Role of Vasopressin in Rat Models of Salt-Dependent Hypertension.
AB  - PURPOSE OF REVIEW: Dietary salt intake increases both plasma sodium and
      osmolality and therefore increases vasopressin (VP) release from the
      neurohypophysis. Although this effect could increase blood pressure by inducing
      fluid reabsorption and vasoconstriction, acute activation of arterial
      baroreceptors inhibits VP neurons via GABAA receptors to oppose high blood
      pressure. Here we review recent findings demonstrating that this protective
      mechanism fails during chronic high salt intake in rats. RECENT FINDINGS: Two
      recent studies showed that chronic high sodium intake causes an increase in
      intracellular chloride concentration in VP neurons. This effect causes GABAA
      receptors to become excitatory and leads to the emergence of VP-dependent
      hypertension. One study showed that the increase in intracellular chloride was
      provoked by a decrease in the expression of the chloride exporter KCC2 mediated
      by local secretion of brain-derived neurotrophic factor and activation of TrkB
      receptors. Prolonged high dietary salt intake can cause pathological plasticity
      in a central homeostatic circuit that controls VP secretion and thereby
      contribute to peripheral vasoconstriction and hypertension.

PMID- 28451856
TI  - Growth performance of broilers fed on sprouted-roasted guar bean (Cyamopsis
      tetragonoloba) based diets.
AB  - In a completely randomized block design with 96 Cobb-500 broilers, a study was
      conducted to evaluate the potential of dietary inclusion of sprouted then roasted
      guar bean in broiler diets. The 96 male day-old broiler chicks, blocked by pen
      into equal weight groups of six chicks replicated four times per treatment, were
      randomly allocated to treatment diets containing graded levels of sprouted then
      roasted guar bean meal (GBM) at 0, 50, 100 and 150 g kg-1 inclusion level. The
      guar bean was sprouted and roasted to reduce guar gum effect. Total feed intake
      decreased significantly as the guar bean meal content increased in the starter
      phase (P < 0.05), but no significant differences in intake of the finisher phase
      (P > 0.05) were observed. Diets containing 0 and 50 g kg-1 GBM recorded
      significantly higher total feed intake compared to the diet containing 150 g kg-1
      GBM. Although average weight gain was not significantly different in birds fed 0
      and 50 g kg-1 GBM diets, it was significantly higher than in birds fed on 100 and
      150 g kg-1 GBM diets. Feed conversion ratio was not significantly different among
      treatment groups (P > 0.05) but showed a general decreasing trend with increasing
      guar bean meal inclusion level, the effect being more pronounced during the
      starter phase. In conclusion, the optimum inclusion level of sprouted then
      roasted guar bean meal in broiler diets is 50 g kg-1.

PMID- 28451857
TI  - Assessing the environmental hazard of individual and combined pharmaceuticals:
      acute and chronic toxicity of fluoxetine and propranolol in the crustacean
      Daphnia magna.
AB  - Pharmaceuticals are widespread emerging contaminants and, like all pollutants,
      are present in combination with others in the ecosystems. The aim of the present
      work was to evaluate the toxic response of the crustacean Daphnia magna exposed
      to individual and combined pharmaceuticals. Fluoxetine, a selective serotonin re
      uptake inhibitor widely prescribed as antidepressant, and propranolol, a non
      selective beta-adrenergic receptor-blocking agent used to treat hypertension,
      were tested. Several experimental trials of an acute immobilization test and a
      chronic reproduction test were performed. Single chemicals were first tested
      separately. Toxicity of binary mixtures was then assessed using a fixed ratio
      experimental design. Five concentrations and 5 percentages of each substance in
      the mixture (0, 25, 50, 75, and 100%) were tested. The MIXTOX model was applied
      to analyze the experimental results. This tool is a stepwise statistical
      procedure that evaluates if and how observed data deviate from a reference model,
      either concentration addition (CA) or independent action (IA), and provides
      significance testing for synergism, antagonism, or more complex interactions.
      Acute EC50 values ranged from 6.4 to 7.8 mg/L for propranolol and from 6.4 to 9.1
      mg/L for fluoxetine. Chronic EC50 values ranged from 0.59 to 1.00 mg/L for
      propranolol and from 0.23 to 0.24 mg/L for fluoxetine. Results showed a
      significant antagonism between chemicals in both the acute and the chronic
      mixture tests when CA was adopted as the reference model, while absence of
      interactive effects when IA was used.

PMID- 28451858
TI  - Biomechanical in vitro comparison of radiofrequency kyphoplasty and balloon
      kyphoplasty.
AB  - PURPOSE: Balloon kyphoplasty (BK) has emerged as a popular method for treating
      osteoporosis vertebral compression fractures (OVCFs). In response to several
      shortcomings of BK, alternative methods have been introduced, among which is
      radiofrequency kyphoplasty (RFK). Biomechanical comparisons of BK and RFK are
      very sparse. The purpose of this study was to perform a biomechanical study in
      which BK and RFK are compared. METHODS: Each of the two study groups comprised
      six specimens prepared from two functional spinal units (FSUs) cut from fresh
      frozen cadaveric spines (3 of T9-T11 and 3 of T12-L2). VCFs (A1.2 type) were
      created in the middle VB of each of the FSUs, with a height loss of 30% of the
      VB. After that, the specimens were subjected to cyclic compression-compression
      loading. The following parameters were determined: range of motion (ROM), height
      of the middle VB, augmentation time, cement interdigitation and cement
      distribution. Also, the cement layer, the trabecular bone in the augmented VB and
      the bone-cement interface were examined for cracks. All of these parameters were
      determined at various stages, namely in the intact middle VB and after its
      fracture, cement augmentation and subject to the cyclic loading protocol.
      RESULTS: Fractures caused a significant increase in median ROM and a significant
      reduction in the height of fractured VB. Cement augmentation significantly
      stabilized the fractures and led to partial height restoration. ROM and vertebral
      height, however, were not restored to the intact levels. Cyclic loading led to a
      further significant increase in ROM and a significant height reduction. There
      were no significant differences between BK and RFK in terms of any of these
      parameters. CONCLUSIONS: BK and RFK achieved similar results for fracture
      stabilization and restoration of the height of the fractured VB. RFK involved
      shorter cement augmentation time and less damage to the trabecular bone.

PMID- 28451859
TI  - Effect of correction surgery for cervical kyphosis on compensatory mechanisms in
      overall spinopelvic sagittal alignment.
AB  - PURPOSE: Progression of kyphotic deformity at the middle/lower cervical spine can
      cause difficulty with horizontal gaze, so compensation at other spinopelvic parts
      may occur. However, the precise mechanism remains unclear. The present study
      investigated the effect of correction surgery for cervical kyphosis on the
      compensatory mechanisms in overall spinopelvic sagittal alignment. METHODS: Forty
      one patients, comprising 23 males and 18 females (mean age 67 years), underwent
      correction surgery for cervical kyphosis using the posterior screw-rod system.
      Spinopelvic lateral radiographs in the standing position were taken before and
      after surgery. C0-1 angle, C1-2 angle, clivo-axial angle (CAA), C2-7 angle,
      thoracic kyphosis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral
      slope were measured. Correlations between C2-7 angle and these parameters before
      surgery, and correlations between the correction angle of cervical kyphosis and
      postoperative changes of these parameters were evaluated. RESULTS: Negative
      correlations were found between the C2-7 angle and CAA (R = -0.640, p < 0.01),
      and C2-7 angle and C0-1 angle (R = -0.762, p < 0.001) before surgery. Negative
      correlations were found between the correction angle of C2-7 and change of CAA (R
      = -0.718, p < 0.001), and between the correction angle of C2-7 and change of C0-1
      angle (R = -0.672, p < 0.01) after surgery. CONCLUSIONS: The present study
      demonstrated that C0-1 angle and CAA are more important in the compensatory
      mechanism for kyphotic deformity at the middle/lower cervical spine compared to
      downward parameters. That is, to maintain horizontal gaze, lordosis increases at
      the cranio-cervical junction with greater kyphosis at the middle/lower cervical
      spine. Correction of cervical kyphosis in the middle/lower cervical spine
      resulted in normalization of the C0-1 angle and CAA because the compensatory
      mechanism at the cranio-cervical junction for obtaining horizontal gaze was no
      longer necessary after surgical intervention.

PMID- 28451860
TI  - Erratum to: Spinopelvic parameter changes and low back pain improvement due to
      femoral neck anteversion in patients with severe unilateral primary hip
      osteoarthritis undergoing total hip replacement.

PMID- 28451862
TI  - CORR Insights(r): What is the Long-term Economic Societal Effect of
      Periprosthetic Infections After THA? A Markov Analysis.

PMID- 28451863
TI  - Variations in Knee Kinematics After ACL Injury and After Reconstruction Are
      Correlated With Bone Shape Differences.
AB  - BACKGROUND: The factors that contribute to the abnormal knee kinematics after
      anterior cruciate ligament (ACL) injury and ACL reconstruction remain unclear.
      Bone shape has been implicated in the development of hip and knee osteoarthritis,
      although there is little knowledge about the effects of bone shape on knee
      kinematics after ACL injury and after ACL reconstruction. QUESTIONS/QUESTIONS:
      (1) What is the relationship between bony morphology with alterations in knee
      kinematics after ACL injury? (2) Are baseline bone shape features related to
      abnormal knee kinematics at 12 months after ACL reconstruction? METHODS: Thirty
      eight patients (29 +/- 8 years, 21 men) were prospectively followed after acute
      ACL injury and before ligamentous reconstruction. Patients were excluded if there
      was a history of prior knee ligamentous injury, a history of inflammatory
      arthritis, associated meniscal tears that would require repair, or any prior knee
      surgery on either the injured or contralateral side. In total, 54 patients were
      recruited with 42 (78%) patients completing 1-year followup and four patients
      excluded as a result of incomplete or unusable imaging data. MR images were
      obtained for the bilateral knees at two time points 1 year apart for both the
      injured (after injury but before reconstruction and 1 year after reconstruction)
      and contralateral uninjured knees. Kinematic MRI was performed with the knee
      loaded with 25% of total body weight, and static images were obtained in full
      extension and in 30 degrees  of flexion. The side-to-side difference (SSD)
      between tibial position in the extended and flexed positions was determined for
      each patient. Twenty shape features, referred to as modes, for the tibia and
      femur each were extracted independently from presurgery scans with the principal
      component analysis-based statistical shape modeling algorithm. Spearman rank
      correlations were used to evaluate the relationship between the SSD in tibial
      position and bone shape features with significance defined as p < 0.05. Each of
      the shape features (referred to as the bone and mode number such as Femur 18 for
      the 18th unique femoral bone shape) associated with differences in tibial
      position was then investigated by modeling the mean shape +/- 3 SDs. RESULTS: Two
      of the 20 specific femur bone shape features (Femur 10, Femur 18) and two of the
      20 specific tibial bone shape features (Tibia 19, Tibia 20) were associated with
      an increasingly anterior SSD in the tibial position for the patients with ACL
      injury before surgical treatment. The shape features described by these modes
      include the superoinferior height of the medial femoral condyle (Femur 18; rho =
      0.33, p = 0.040); the length of the anterior aspect of the lateral tibial plateau
      (Tibia 20; rho = -0.35, p = 0.034); the sphericity of the medial femoral condyle
      (Femur 10; rho = -0.52, p < 0.001); and tibial slope (Tibia 19; rho = 0.34; p =
      0.036). One year after surgical treatment, there were two of 20 femoral shape
      features that were associated with SSD in the tibial position in extension (Femur
      10, Femur 18), one of 20 femoral shape features associated with SSD in the tibial
      position in flexion (Femur 10), and three of 20 tibial shape features associated
      with SSD in the tibial position in flexion (Tibia 2, Tibia 4, Tibia 19). The
      shape features described by these modes include the sphericity of the medial
      femoral condyle (Femur 10; rho = -0.38, p = 0.020); the superoinferior height of
      the medial femoral condyle (Femur 18; rho = 0.34, p = 0.035); the height of the
      medial tibial plateau (Tibia 2; rho = -0.32, p = 0.048); the AP length of the
      lateral tibial plateau (Tibia 4; rho = -0.37, p = 0.021); and tibial slope (Tibia
      19; rho = 0.34, p = 0.038). CONCLUSIONS: We have observed multiple bone shape
      features in the tibia and the femur that may be associated with abnormal knee
      kinematics after ACL injury and ACL reconstruction. Future directions of research
      will include the influence of bony morphology on clinical symptoms of instability
      in patients with and without ACL reconstruction and the long-term evaluation of
      these shape factors to better determine specific contributions to posttraumatic
      arthritis and graft failure. LEVEL OF EVIDENCE: Level II, therapeutic study.

PMID- 28451864
TI  - Prolotherapy Induces an Inflammatory Response in Human Tenocytes In Vitro.
AB  - BACKGROUND: Proliferative therapy, or prolotherapy, is a controversial treatment
      method for many connective tissue injuries and disorders. It involves the
      injection of a proliferant, or irritant solution, into the site of injury, which
      causes small-scale cell death. This therapeutic trauma is theorized to initiate
      the body's wound-healing cascade, perhaps leading to tissue repair. The immediate
      effects of many of these proliferants are poorly characterized, as are the
      cellular responses to them; here, we sought to evaluate the immediate effects of
      two common proliferants (dextrose and P2G, a combination of phenol, glucose, and
      glycerin) on the cellular response of human tenocytes, and begin to explicate the
      mechanisms with which each proliferant functions. QUESTIONS/PURPOSES: We asked:
      What are the effects of treating cultured tenocytes with proliferative treatment
      agents on their (1) cellular metabolic activity, (2) RNA expression, (3) protein
      secretion, and (4) cell migration? METHODS: Using human hamstring and Achilles
      tendon cells, we attempted to answer our research questions. We used a
      colorimetric metabolic assay to assess the effect of dextrose and P2G proliferant
      treatment on cell mitochondrial activity compared with nontreated tenocytes.
      Next, using quantitative PCR, ELISA, and a reporter cell line, we assessed the
      expression of several key markers involved in tendon development and
      inflammation. In addition, we used a scratch wound-healing assay to evaluate the
      effect of proliferant treatment on tenocyte migration. RESULTS: Results showed
      that exposure to both solutions led to decreased metabolic activity of tenocytes,
      with P2G having the more pronounced effect (75% +/- 7% versus 95% +/- 7% of
      untreated control cell metabolic levels) (ANOVA; p < 0.01; mean difference,
      0.202; 95% CI, 0.052-0.35). Next, gene expression analysis confirmed that
      treatment led to the upregulation of key proinflammatory markers including
      interleukin-8 and cyclooxygenase-2 and downregulation of the matrix marker
      collagen type I. Furthermore, using a reporter cell line for transforming growth
      factor-beta (TGF-beta), a prominent antiinflammatory marker, we showed that
      treatments led to decreased TGF-beta bioactivity. Analysis of soluble proteins
      using ELISA revealed elevated levels of soluble prostaglandin E2 (PGE2), a
      prominent inducer of inflammation. Finally, both solutions led to decreased
      cellular migration in the tenocytes. CONCLUSIONS: Taken together, these results
      suggest that prolotherapy, more so with P2G, may work by decreasing cellular
      function and eliciting an inflammatory response in tenocytes. Additional studies
      are needed to confirm the cellular signaling mechanisms involved and the
      resulting immediate response in vivo. CLINICAL RELEVANCE: If these preliminary in
      vitro findings can be confirmed in an in vivo model, they may provide clues for a
      possible cellular mechanism of a common alternative treatment method currently
      used for certain soft tissue injuries.

PMID- 28451865
TI  - Tackling the perils of unawareness: the cluster headache case.

PMID- 28451866
TI  - The 116G > A MSH6 and IVS1-1121C > T PMS2 Genes Polymorphisms Modulate the Risk
      of the Sporadic Colorectal Cancer Development in Polish Population.
AB  - Colorectal cancer (CRC) is one of the most common cancers worldwide. DNA mismatch
      repair (MMR) is an evolutionarily conserved process that corrects mismatches
      generated during DNA replication. MMR defects were found to be associated with
      hereditary non-polyposis colorectal cancer (HNPCC) and a subset of sporadic colon
      cancers. The inheritance of common variations in MMR genes may influences
      individual susceptibility to the development of colorectal cancer. The purpose of
      the study was to evaluate the association between gene polymorphisms Glu39Gly
      (c.116G > A) of MSH6 gene and IVS1-1121C > T of PMS2 gene and sporadic colorectal
      cancer risk, in a case-control study comprising 200 patients and 200 controls
      origination from polish population. DNA was isolated from peripheral blood
      lymphocytes of enrolled patients, and gene polymorphisms were analysed by
      restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) for
      MSH6 and TaqMan for PMS2. G/A variant of Glu39Gly (c.116G > A) genotype was
      associated with an increased risk of colorectal cancer (OR 1,65 95%CI:1,01-2,69 p
      = 0.44). Presence of A allele was also significantly higher in patient with CRC
      (OR 1,57 95% CI: 1,04-2,38 p = 0.032). Prevalence of this genotype was also
      markedly higher in females and patients above 60 years in CRC group (OR 2.25
      95%CI: 1.22-4.14 p = 0.0098 and OR 2.74 95% CI: 1.27-5.93 p = 0.0097
      respectively). None of such correlations was observed for genotype variants of
      IVS1-1121C > T PMS2. In conclusion, our data suggests thatMSH6 Glu39Gly
      polymorphism is associated with the risk of developing sporadic colorectal cancer
      in polish population. Linkage to the female gender, onset above 60 years old and
      further increase of risk when combined with wild-type allele of PMS2 IVS1-1121C >
      T polymorphism indicates defective mismatch repair system.

PMID- 28451867
TI  - Prevalence and Incidence Trends for Diagnosed Prescription Opioid Use Disorders
      in the United Kingdom.
AB  - INTRODUCTION: The prevalence of prescription opioid use disorders in the US has
      increased markedly in parallel with increases in opioid prescribing. Whilst an
      increase in opioid prescribing has also occurred in the UK, it remains unknown if
      there have been concurrent increases in opioid use disorders. The aim of this
      study was to examine national trends in the prevalence and incidence of physician
      diagnosed opioid use disorders in the UK. METHODS: In a retrospective electronic
      health care database analysis using data from the UK Clinical Practice Research
      Datalink (CPRD), we identified persons receiving a first opioid prescription
      between January 1, 2008 and December 31, 2012. Persons with an opioid use
      disorder were identified by Read codes assigned by patients' physicians within 6
      months following an opioid prescription. We calculated prevalence and incidence
      rates by dividing the analysis population by the total number of patients exposed
      (prevalence) or the total patient-years of exposure (incidence) using the 'exact'
      Clopper-Pearson Binomial method. RESULTS: Our analysis included 714,699 person
      years of prescription opioid exposure. The 5-year period prevalence of opioid use
      disorders was 4.61 (95% CI 4.28-4.96) per 10,000 individuals, or 0.05%. The
      incidence rate of opioid use disorders was of 6.51 (95% CI 5.93-7.13) patients
      per 10,000 patient-years exposed. When examined by study year, there was no clear
      suggestion of a changing trend over time. When stratified by opioid drug, trends
      in the incidence rate during the study were either stable (i.e., codeine and
      tramadol), increasing (i.e., morphine) or decreasing (i.e., dihydrocodeine).
      CONCLUSIONS: Our study demonstrates that despite the marked increase in overall
      opioid prescribing in the UK in the past decade, there has not been an increase
      in the incidence of physician-diagnosed opioid use disorders.

PMID- 28451868
TI  - Juglone alleviates pneumolysin-induced human alveolar epithelial cell injury via
      inhibiting the hemolytic activity of pneumolysin.
AB  - Streptococcus pneumoniae (the pneumococcus) is an opportunistic pathogen
      responsible for several human diseases, including acute otitis media, pneumonia,
      sepsis and bacterial meningitis, and possesses numerous virulence factors
      associated with pneumococcal infection and pathogenesis. With the capacity to
      form pores in cholesterol-rich membranes, pneumolysin (PLY) is a key virulence
      factor of S. pneumoniae and causes severe tissue damage during pneumococcal
      infection. Juglone (JG), a natural 1,4-naphthoquinone widely found in the roots,
      leaves, woods and fruits of Juglandaceae walnut trees, inhibits PLY-induced
      hemolysis via inhibition of the oligomerization of PLY and exhibits minimal anti
      S. pneumoniae activity. In addition, when human alveolar epithelial (A549) cells
      were co-cultured with PLY and JG, PLY-mediated cell injury was significantly
      alleviated. These results indicate that JG directly interacts with PLY to reduce
      the cytotoxicity of the toxin in human alveolar epithelial cells. Hence, JG is an
      effective inhibitor of PLY and protects lung cells from PLY-mediated cell injury.
      This study also provides the basis for the development of anti-virulence drugs
      for the treatment of S. pneumoniae infections.

PMID- 28451869
TI  - Contribution of subjective Disease Activity Score 28 (DAS28) components to the
      response to treatment of rheumatoid arthritis.
AB  - We investigated the contributions made by the subjective components of the
      Disease Activity Score 28 (DAS28) to the treatment response of rheumatoid
      arthritis (RA). In addition, factors associated with poor response to treatment
      at 6 months, despite normalization of objective measures, were examined. A total
      of 426 newly diagnosed RA patients were included. The DAS28-P score (the
      subjective components of the DAS28 relative to the total components) was
      calculated as DAS28-P = 0.56 * sqrt(TJC28) + 0.014 * (VAS-GH) /0.56 * sqrt(TJC28)
      + 0.28 * sqrt(SJC28) + 0.7 * In(erythrocyte sedimentation rate (ESR)) + 0.014 *
      (VAS-GH). The European League Against Rheumatism (EULAR) response was assessed
      after 6 months of treatment. Of those who failed to attain good EULAR responses,
      those for whom the objective measures (the ESR, the C-reactive protein level, and
      swollen joints) were normalized were defined as having failed treatment because
      of subjective measures. The median (IQR) DAS28 score at baseline was 4.8 (4.04
      5.49) and that after 6 months of treatment 3.21 (2.41-3.95). The DAS28-P score
      fell significantly from baseline to 6 months in good (0.43 versus 0.28, p <
      0.001) and moderate responders (0.44 versus 0.4, p = 0.003), but not in non
      responders (0.43 versus 0.45, p = 0.727). Younger age, a lower DAS28 score, and a
      lower DAS28-P score at baseline were related to a good EULAR response. Subjects
      who failed to respond because of subjective measures tended to have higher DAS28
      P scores at baseline. We found that RA patients with high DAS28-P scores,
      reflecting subjective measures, were less likely to achieve good EULAR responses
      6 months after treatment initiation and tended not to be classified as good
      responders despite normalization of objective measures.

PMID- 28451870
TI  - Association between serum and synovial fluid Dickkopf-1 levels with radiographic
      severity in primary knee osteoarthritis patients.
AB  - Primary knee osteoarthritis (OA) contributes to disability among middle-aged and
      elderly people. Dickkopf-1 (Dkk-1) and sclerostin are inhibitors of Wnt/beta
      catenin signaling pathway implicated in regulation of cartilage homeostasis and
      bone formation, respectively. We aim to investigate the association between the
      serum(s) and synovial fluid (SF) Dkk-1 and sclerostin levels and disease severity
      in patients with primary knee OA. Forty patients aged 56-87 years with primary
      knee OA and 20 healthy individuals were recruited. Weight-bearing anteroposterior
      radiographs of the affected knee were used to determine the disease severity
      according to Kellgren and Lawrence criteria. Dkk-1 and sclerostin levels in serum
      and SF were measured by ELISA. SF Dkk-1 levels were significantly higher in the
      OA, compared to control group (180 +/- 182 vs 128 +/- 330 pg/ml, p < 0.001).
      However, OA patients did not differ significantly regarding the sDkk-1
      concentrations compared to healthy controls (1289.8 pg/ml vs 1214.1,
      respectively, p = 0.630). SF Dkk-1 levels in Kellgren and Lawrence (KL) grade 4
      were significantly elevated compared to those of KL grades 2 and 3 (1.97 vs 2.23
      pg/ml, p = 0.017, log transformed because data were not normally distributed),
      whereas sDkk-1 levels between those groups demonstrated marginally statistically
      significant difference (1111.8 vs 1415.9 pg/ml, p = 0.057). SFSclerostin and
      sSclerostin levels did not have any significant difference between the OA and
      control groups. SF Dkk-1 levels are positively related to the severity of joint
      damage in knee OA. Sclerostin levels failed to substantiate an association to
      knee OA progression. Dkk-1 could play a potential role in the degenerative
      process of OA. Thus, DKK-1 may emerge as a promising future therapeutic
      manipulation of OA.

PMID- 28451871
TI  - The impact of peer victimization and psychological symptoms on quality of life in
      children and adolescents with systemic lupus erythematosus.
AB  - There is no documentation about the association between peer victimization,
      psychological status, and quality of life (QOL) in children and adolescents with
      systemic lupus erythematosus (SLE). The aim of this study was to evaluate the
      association between peer victimization, psychological symptoms, and QOL in a
      cohort of children and adolescents with SLE. Forty-one patients (aged 9-18 years)
      participated in this study. The control group (n = 49) was composed of healthy
      children and adolescents from local community. Questionnaires were used to
      evaluate the peer victimization, psychological status, and QOL of children and
      adolescents with and without SLE. No significant difference was found between the
      study and control groups for peer victimization, depression, state and trait
      anxiety, and QOL scores. The peer victimization, depression, anxiety, and self
      esteem scores were negatively correlated with psychosocial and total subscale
      scores of QOL in the study group. According to regression analyses, trait anxiety
      had a negative predictive effect on the physical health domain scores of QOL,
      whereas trait anxiety and peer victimization had a negative effect on the
      psychosocial domain and total scores of QOL in the SLE patients. This study
      suggests that trait anxiety and peer victimization are risk factors for poor QOL
      in adolescents with SLE.

PMID- 28451872
TI  - The relationship between disease activity, quality of life, and personality types
      in rheumatoid arthritis and ankylosing spondylitis patients.
AB  - We hypothesized that clinical outcomes might be influenced by personality type
      (A, B, C, D) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). One
      hundred ninety-four patients (104 with RA, 90 with AS) participated in a
      questionnaire study. We evaluated health-related quality of life (HRQoL) using
      the Medical Outcome Study Short-Form 36 (SF-36), personality type A/B with the
      Jenkins Activity Survey, type C with the State-Trait Anger Expression Inventory
      Anger-in Scale, type D with the Type D Personality Scale, and disease activity
      with Disease Activity Score with 28 joints for RA and Bath Ankylosing Spondylitis
      Disease Activity Index for AS. We used Pearson's correlation coefficient,
      independent samples t tests, and multivariate analyses of variance. In the RA
      group, type D personality was significantly correlated with 7/12 SF-36
      components. AS patients with type D personality had deficits in all SF-36
      subscales. Type D was related with higher disease activity in RA and AS. Both RA
      and AS type C patients had more active disease forms and negatively affected
      HRQoL subscales. In the RA group, type A personality did not correlate with
      HRQoL, but it positively influenced pain visual analog scale scores. In AS
      patients, type A personality was linked with higher HRQoL and with less active
      disease. Type C and type D personality types were correlated with decreased HRQoL
      and higher disease activity in RA and AS patients. Type A personality was
      associated with less active disease and higher HRQoL in AS patients and with less
      pain in RA patients.

PMID- 28451873
TI  - Association of anti-triosephosphate isomerase antibodies with aseptic meningitis
      in patients with neuropsychiatric systemic lupus erythematosus.
AB  - Autoantibodies to triosephosphate isomerase (TPI), which is an important
      glycolytic enzyme in red blood cells and neuronal cells, have been reported to be
      associated with neuropsychiatric systemic lupus erythematosus (NPSLE)
      pathogenesis. However, the clinical features regarding anti-TPI antibody (anti
      TPI)-positive NPSLE are not yet known. The aim of this study is to investigate
      the clinical features of anti-TPI-positive NPSLE patients using anti-TPI index
      values determined by enzyme-linked immunosorbent assay (ELISA). Thirty-one NPSLE
      patients treated in our department were included in this study. Serum samples
      were collected, and serum anti-TPI titers were measured by ELISA. The anti-TPI
      index values were defined as follows: (OD405 of samples - OD405 of negative
      control)/(OD405 of positive control - OD405 of negative control) * 100. Anti-TPI
      index values greater than 2 standard deviations above the mean of healthy
      controls were regarded as positive. The clinical features of anti-TPI-positive
      and anti-TPI-negative NPSLE were compared. Ten of the 31 NPSLE patients had anti
      TPI positivity (32.3%). The clinical features of anti-TPI-positive NPSLE were
      comparable with those of anti-TPI-negative NPSLE, except for a higher frequency
      of aseptic meningitis (p = 0.027) and a lower frequency of acute confusional
      state (P = 0.026). Laboratory data in patients with anti-TPI-positive NPSLE
      showed significantly higher serum IgG levels. Furthermore, anti-TPI index values
      positively correlated with serum IgG levels. Our study indicates that serum anti
      TPI increases in the presence of elevated IgG levels and can be associated with
      the pathogenesis of aseptic meningitis in NPSLE.

PMID- 28451874
TI  - Characterization of 32 microsatellite loci for the Pacific red snapper, Lutjanus
      peru, through next generation sequencing.
AB  - We developed a set of hypervariable microsatellite markers for the Pacific red
      snapper (Lutjanus peru), an economically important marine fish for small-scale
      fisheries in the west coast of Mexico. We performed shotgun genome sequencing
      with the 454 XL titanium chemistry and used bioinformatic tools to search for
      perfect microsatellite loci. We selected 66 primer pairs that were synthesized
      and genotyped in an ABI PRISM 3730XL DNA sequencer in 32 individuals from the
      Gulf of California. We estimated levels of genetic diversity, deviations from
      linkage and Hardy-Weinberg equilibrium, estimated the frequency of null alleles
      and the probability of individual identity for the new markers. We reanalyzed 16
      loci in 16 individuals to estimate genotyping error rates. Eighteen loci failed
      to amplify, 16 loci were discarded due to unspecific amplifications and 32 loci
      (14 tetranucleotide and 18 dinucleotide) were successfully scored. The average
      number of alleles per locus was 21 (+/-6.87, SD) and ranged from 8 to 34. The
      average observed and expected heterozygosities were 0.787 (+/-0.144 SD, range
      0.250-0.935) and 0.909 (+/-0.122 SD, range 0.381-0.965), respectively. No
      significant linkage was detected. Eight loci showed deviations from Hardy
      Weinberg equilibrium, and from these, four loci showed moderate null allele
      frequencies (0.104-0.220). The probability of individual identity for the new
      loci was 1.46-62. Genotyping error rates averaged 9.58%. The new markers will be
      useful to investigate patterns of larval dispersal, metapopulation dynamics, fine
      scale genetic structure and diversity aimed to inform the implementation of
      spatially explicit fisheries management strategies in the Gulf of California.

PMID- 28451875
TI  - Prevalence of Gabapentin Abuse: Comparison with Agents with Known Abuse Potential
      in a Commercially Insured US Population.
AB  - BACKGROUND: Despite international calls to make gabapentin a controlled
      substance, studies of gabapentin use/abuse patterns are limited to small/high
      risk samples and adverse event reports. OBJECTIVE: The aim of this study was to
      conduct a systematic assessment of the abuse potential/prevalence of gabapentin
      in a large sample. DATA SOURCE: Truven Health MarketScan(r) Commercial Claims and
      Encounters database, years 2013-2015. ELIGIBILITY CRITERIA: Patients with two or
      more claims for one or more abusable drugs and >=12 months' continuous enrollment
      were sampled for Lorenz curve analysis. Prevalence analysis was limited to those
      with >=120 days of therapy. METHODS: Abuse potential was measured as Lorenz-1
      (consumption of drug supply by top 1% of users) of >=15%. Dose thresholds were
      morphine milligram equivalent (MME) standards for opioids, and maximum labeled
      doses in milligrams (mg) for other drugs. RESULTS: Lorenz-1 values were 37%
      opioids, 19% gabapentin, 15% pregabalin, 14% alprazolam, and 13% zolpidem. The
      top 1% gabapentin users filled prescriptions for a mean (median) 11,274 (9534)
      mg/day, more than three times the recommended maximum (3600 mg). Of these, one
      quarter used or diverted >=12,822 mg/day. The top 1% opioid and pregabalin users
      filled prescriptions for a mean (median) 180 (127) MMEs and 2474 (2219) mg/day,
      respectively. Of patients using opioids + gabapentin simultaneously, 24% had
      three or more claims exceeding the dose threshold within 12 months. LIMITATIONS:
      Established threshold criteria for gabapentinoid abuse are uncertain. Indications
      for gabapentinoid use (e.g. hot flashes, restless legs syndrome) were not
      measured. CONCLUSION: Gabapentin use patterns are similar to those of other
      abusable medications. High daily doses pose safety and/or diversion concerns, and
      investigation of the medical consequences of gabapentin abuse is needed.

PMID- 28451876
TI  - An Exploration of Genetic Test Utilization, Genetic Counseling, and Consanguinity
      within the Inborn Errors of Metabolism Collaborative (IBEMC).
AB  - The Inborn Errors of Metabolism Collaborative (IBEMC) includes clinicians from 29
      institutions collecting data to enhance understanding of metabolic conditions
      diagnosable by newborn screening. Data collected includes hospitalizations, test
      results, services, and long-term outcomes. Through evaluation of this data, we
      sought to determine how frequently genetic counseling had been provided, how
      often genetic testing was performed, and also determine the consanguinity rate in
      this population. A data query was performed with the following elements
      abstracted/analyzed: current age, metabolic condition, whether genetic counseling
      was provided (and by whom), whether genetic testing was performed, and
      consanguinity. Genetic counseling was provided to families 95.8% of the time and
      in 68.6% of cases by a genetic counselor. Genetic testing was performed on 68.0%
      of subjects, with usage highest for fatty-acid-oxidation disorders (85.1%). The
      rate of consanguinity was 2.38%. Within this large national collaborative there
      is a high frequency of genetic counseling, though in one-third of cases a genetic
      counselor has not been involved. Additionally, while metabolic conditions have
      historically been diagnosed biochemically, there is currently high utilization of
      molecular testing suggesting DNA testing is being incorporated into diagnostic
      assessments - especially for fatty-acid-oxidation disorders where the underlying
      genotype helps predict clinical presentation.

PMID- 28451878
TI  - Differential expression of myocardial heat shock proteins in rats acutely exposed
      to fluoride.
AB  - Acute fluoride (F-) toxicity is known to cause severe cardiac complications and
      leads to sudden heart failure. Previously, we reported that increased myocardial
      oxidative damage, apoptosis, altered cytoskeleton and AMPK signaling proteins
      associated with energy deprivation in acute F- induced cardiac dysfunction. The
      present study was aimed to decipher the status of myocardial heat shock proteins
      (Hsps-Hsp27, Hsp32, Hsp40, Hsp60, Hsp70, Hsp90) and heat shock transcription
      factor 1 (Hsf1) in acute F--intoxicated rats. In order to study the expression of
      myocardial Hsps, male Wistar rats were treated with single oral doses of 45 and
      90 mg/kg F- for 24 h. The expression levels of myocardial Hsps were determined
      using RT-PCR, western blotting, and immunohistochemical studies. Acute F-
      intoxicated rats showed elevated levels of both the transcripts and protein
      expression of Hsf1, Hsp27, Hsp32, Hsp60, and Hsp70 when compared to control. In
      addition, the expression levels of Hsp40 and Hsp90 were significantly declined in
      a dose-dependent fashion in F--treated animals. Our result suggests that
      differential expression of Hsps in the rat myocardium could serve as a balance
      between pro-survival and death signal during acute F--induced heart failure.

PMID- 28451879
TI  - Dynamical persistence of active sites identified in maltose-binding protein.
AB  - This study identifies dynamical properties of maltose-binding protein (MBP)
      useful in unveiling active site residues susceptible to ligand binding. The
      described methodology has been previously used in support of novel topological
      techniques of persistent homology and statistical inference in complex, multi
      scale, high-dimensional data often encountered in computational biophysics. Here
      we outline a computational protocol that is based on the anisotropic elastic
      network models of 14 all-atom three-dimensional protein structures. We introduce
      the notion of dynamical distance matrices as a measure of correlated interactions
      among 370 amino acid residues that constitute a single protein. The dynamical
      distance matrices serve as an input for a persistent homology suite of codes to
      further distinguish a small subset of residues with high affinity for ligand
      binding and allosteric activity. In addition, we show that ligand-free closed MBP
      structures require lower deformation energies than open MBP structures, which may
      be used in categorization of time-evolving molecular dynamics structures.
      Analysis of the most probable allosteric coupling pathways between active site
      residues and the protein exterior is also presented.

PMID- 28451880
TI  - Racemization and transesterification of alkyl hydrogeno-phenylphosphinates.
AB  - In this article, we explore, both theoretically and experimentally, the general
      reactivity of alkyl hydrogeno-phenylphosphinates with alcohols. We show that
      alcohol molecules act exclusively as nucleophilic species, and add to alkyl
      hydrogeno-phenylphosphinates, leading to pentacoordinated intermediates. These
      intermediates are shown to subsequently competitively undergo alcohol
      eliminations and/or Berry pseudorotations. This offers several possible routes
      for racemizations and/or alcohol exchange reactions. Transition standard Gibbs
      free energies predicted from DFT calculations for the overall alcohol exchange
      mechanism are shown to be compatible with those experimentally measured in case
      ethanol reacts with ethyl hydrogeno-phenylphosphinate (134.5~136.0 kJ mol-1 at 78
      degrees C). Graphical abstract ?.

PMID- 28451877
TI  - Vitamin-D concentrations, cardiovascular risk and events - a review of
      epidemiological evidence.
AB  - Vitamin D has long been established as an elemental factor of bone physiology.
      Beyond mineral metabolism, the expression of the vitamin D receptor has been
      identified throughout the cardiovascular (CV) system. Experimental studies showed
      beneficial effects of vitamin D on heart and vessels, but vitamin D intoxication
      in animals also led to hypercalcemia and vascular calcification. Our knowledge
      has been extended by epidemiological studies that showed that 25-hydroxyvitamin D
      (25(OH)D) levels are inversely associated with an increased CV risk itself, but
      also with established CV risk factors, such as arterial hypertension, endothelial
      dysfunction and atherosclerosis. Conversely, randomized controlled trials could
      not document significant and consistent effects of vitamin D supplementation on
      CV risk or events. Potential explanations may lie in differences in reference
      ranges or the possibility that low vitamin D in CV disease is only an
      epiphenomenon. In the latter case, the key question is why low 25(OH)D levels are
      such a strong predictor of health. While we wait for new data, the current
      conclusion is that vitamin D is a strong risk marker for CV risk factors and for
      CV diseases itself.

PMID- 28451881
TI  - Theoretical study of the H + HCN -> H + HCN process.
AB  - We present a theoretical study on the detailed mechanism and kinetics of the H +
      HCN -> H + HNC process. The potential energy surface was calculated at the
      complete basis set quantum chemical method, CBS-QB3. The vibrational frequencies
      and geometries for four isomers (H 2CN, cis-HCNH, trans-HCNH, CNH 2), and seven
      saddle points (TSn where n = 1 - 7) are very important and must be considered
      during the process of formation of the HNC in the reaction were calculated at the
      B3LYP/6-311G(2d,d,p) level, within CBS-QB3 method. Three different pathways (PW1,
      PW2, and PW3) were analyzed and the results from the potential energy surface
      calculations were used to solve the master equation. The results were employed to
      calculate the thermal rate constant and pathways branching ratio of the title
      reaction over the temperature range of 300 up to 3000 K. The rate constants for
      reaction H + HCN -> H + HNC were fitted by the modified Arrhenius expressions.
      Our calculations indicate that the formation of the HNC preferentially occurs via
      formation of cis-HCNH, the fitted expression is k P W2(T) = 9.98 * 10-22 T 2.41
      exp(-7.62 kcal.mol-1/R T) while the predicted overall rate constant k O v e r a l
      l (T) = 9.45 * 10-21 T 2.15 exp(-8.56 kcal.mol-1/R T) in cm 3 molecule -1 s -1.
      Graphical Abstract (a) Potential energy surface, (b) thermal rate constants as a
      function of temperature and

PMID- 28451882
TI  - Electrochemical oxygen reduction mechanism on FeN2-graphene.
AB  - Metal-coordinated nitrogen-doped carbons are highly active in promoting
      electrochemical oxygen reduction reactions (ORR). The detailed kinetic and
      thermodynamic ORR behavior on three different FeN2-graphene [FeN2-G (A), (B) and
      (C)] structures was investigated in this work. The results show that formation of
      these FeN2-G configurations is energetically favorable; however, not all of them
      are effective for ORR. The higher HOMO energy and smaller HOMO-LUMO gap of FeN2-G
      (A) and (C) make them have strong adsorption strengths to ORR intermediates,
      which leads to occupation the active sites on the catalysts during ORR, and thus
      loss of catalytic activity. Examination of the results of ?G of each reduction
      step also drew the same conclusion. The ?G of the elementary steps of the ORR at
      zero electrode potential vs. standard hydrogen electrode are downhill only on
      FeN2-G (B). Throughout the entire four-electron ORR, the reduction of O to OH
      displays the highest reaction barrier. When the potential is >0.19 V, the
      reduction of OH species into water is uphill. Therefore, ORR activity is limited
      by two rate-determining steps on FeN2-G (B) at high potential: O and OH reduction
      steps.

PMID- 28451883
TI  - Exohedral complexes of large fullerenes, a theoretical approach.
AB  - The possibility of existence of exohedral organometallic complexes of fullerenes
      larger than C60 in which their coordination can have eta6 hapticity was studied
      from a theoretical point of view. Complexes containing C70, C74 or C60 cages, as
      well as cyclopentadienyl (Cp), pentamethyl-cyclopentadienyl (Me5Cp), benzene
      rings and hexamethyl-phenyl (Me6Ph) fragments as ligands, were designed and
      studied. The results show that many of these molecules can be thermodynamically
      stable and can have electronic interesting behavior.

PMID- 28451884
TI  - Manganese tissue accumulation and tyrosine hydroxylase immunostaining response in
      the Neotropical freshwater crab, Dilocarcinus pagei, exposed to manganese.
AB  - Manganese (Mn) is an essential metal for the development and function of the
      mammalian brain; however, excess Mn accumulation may cause neurological
      abnormalities resembling Parkinson's disease due to reductions in brain dopamine
      levels. Because dopamine also regulates many functions in crustaceans, this study
      examined the effects of Mn accumulation in Dilocarcinus pagei, a Neotropical
      freshwater crab. Following a 72-h exposure to graded concentrations of MnCl2, Mn
      accumulation was assessed in several tissues. Glycaemia and the tyrosine
      hydroxylase (TH) immunostaining response were also examined as indicators of
      catecholaminergic function and catecholaminergic cell integrity, respectively.
      Tissue Mn accumulation was variable and occurred in the following order: gills >
      hepatopancreas > claw muscle > haemolymph. Exposure to 2 mM Mn reduced the gill
      levels of calcium, copper and iron, whereas Mn at all concentrations decreased
      zinc levels. All Mn-exposed animals showed lower copper levels in the
      hepatopancreas and haemolymph. Exposure to 2.0 mM Mn increased the haemolymph
      calcium. Mn exposure had no effect on glycaemia, whereas exposure to low Mn
      concentrations reduced the TH immunostaining response. Analysis of the central
      nervous system revealed the greatest Mn effect in the cerebral ganglion and the
      least effect in the abdominal ganglia. These results suggest the operation of an
      adaptive mechanism for tissue accumulation that could be responsible for the lack
      of an association between Mn concentrations and metal accumulation. The findings
      also suggest that Mn, calcium, iron and zinc share a transporter in gill cells
      and that Mn resistance is greater in the TH-positive cells of this crustacean
      than in mammalian cells.

PMID- 28451886
TI  - 5-LOX in Alzheimer's Disease: Potential Serum Marker and In Vitro Evidences for
      Rescue of Neurotoxicity by Its Inhibitor YWCS.
AB  - The inflammatory process plays a key role in neurodegenerative disorder. The
      inflammatory molecule, 5-lipooxygenase (5-LOX), protein is involved in the
      pathologic phenotype of Alzheimer's disease (AD) which includes Abeta amyloid
      deposition and tau hyperphosphorylation. This study determined the level of 5-LOX
      in serum of AD patients, mild cognitive impairment (MCI) patients, and the normal
      elderly, and the rescue effect by YWCS, a peptide inhibitor of 5-LOX on
      neurotoxicity by Abeta amyloid25-35 (Abeta25-35) in neuroblastoma cells. The
      concentration of serum 5-LOX was estimated by surface plasmon resonance and
      western blot. The neuroprotective effect of 5-LOX peptide inhibitor YWCS in
      Abeta25-35-induced neurotoxicity was analyzed by MTT assay and western blotting.
      We found significant upregulated serum 5-LOX in AD patients and also in MCI
      patients compared to the normal control group. The peptide inhibitor of 5-LOX,
      YWCS, prevented the neurotoxic effect of Abeta25-35 by reducing the expression of
      gamma-secretase as well as p-Tau181 in SH-SY5Y cells. However, YWCS was nontoxic
      towards normal HEK cells. The differential expression of serum 5-LOX among the
      study groups suggests it can be one of potential serum protein marker and a
      therapeutic regimen for AD and MCI. The negative correlation with
      neuropsychological parameters, i.e., MoCA and HMSE, increases its importance and
      makes it useful during the clinical setup which is very needful in developing
      countries. Peptide YWCS can serve as a new platform as a 5-LOX inhibitor which
      can prevent neurotoxicity developed in AD.

PMID- 28451885
TI  - Impact of High-Fat Diet and Early Stress on Depressive-Like Behavior and
      Hippocampal Plasticity in Adult Male Rats.
AB  - During development, the brain goes through fundamental processes, including
      organization of neural networks and plasticity. Environmental interventions may
      change initial brain programming, leading to long-lasting effects and altering
      the susceptibility to psychopathologies, including depression disorder. It is
      known that depression is a psychiatric disorder with a high prevalence worldwide,
      including high rates among adolescents. In this study, we evaluated whether
      social isolation in the prepubertal period and chronic use of high-fat diet (HFD)
      may induce depressive-like behavior in male adult rats. We also investigated
      hippocampal plasticity markers and neurotransmitter systems. We found both social
      isolation and HFD induced a depressive-like behavior in the forced swimming task.
      Moreover, chronic HFD reduced synaptic markers in hippocampus, demonstrated by
      reductions in betaIII-tubulin (neuronal marker), PSD-95, SNAP-25, and
      neurotrophin-3. The HFD group also presented decreased glutamatergic and
      GABAergic receptors subunits. On the other hand, stress affected hippocampal
      brain-derived neurotrophic factor (BDNF) signaling pathways, and increased
      expression of subunit of the NMDA receptor (NR2A). Both factors (stress and diet)
      decreased GR in the hippocampus without affecting plasma corticosterone at basal
      levels. Interactions between early stress and HFD access were observed only in
      the BNDF receptor (tropomyosin receptor kinase B; TrkB) and synaptophysin. In
      summary, these findings showed that a brief social isolation and chronic HFD,
      during a sensitive developmental period, cause depressive-like behavior in
      adulthood. The mechanisms underlying these behavioral effects may involve changes
      in the levels of synaptic proteins in hippocampus: HFD consumption appears to
      affect synaptic markers, while social isolation affected BDNF signaling more
      significantly.

PMID- 28451887
TI  - Bedside Ultrasound After Decompressive Craniectomy: A New Standard?

PMID- 28451888
TI  - Use of an Outreach Coordinator to Reengage and Retain Patients at Risk of Falling
      Out of HIV Care, Does the Amount of Time Matter?
AB  - Retention in care remains a major problem for people living with HIV and it is
      well known that retention in high quality HIV care improves clinical outcomes.
      This project used an outreach coordinator to perform phone and letter
      interventions to improve retention in patients at risk of falling out of care.
      Sixty-one (5%) patients were at risk in 2015 and received an intervention by the
      outreach coordinator. Fifty (82%) had a visit and 22 (36%) met the HRSA
      definition of retention. The mean time per patient was 59 min; therefore, it took
      2.7 h to achieve each retained patient or 1.2 h for each patient with a visit. By
      calculation, minutes over 75 appeared to be the point of diminishing returns.
      Cost analysis resulted in a cost of less than $100 per patient.

PMID- 28451889
TI  - Chronic Pain Predicting Reciprocity of Support Among Vulnerable, Predominantly
      African-American Persons Living with HIV/AIDS.
AB  - Among persons living with HIV/AIDS (PLHIV), approximately two-thirds report
      moderate to severe pain. Chronic pain can negatively affect PLHIVs' health
      behaviors and outcomes by interfering with their reciprocity (mutual exchange) of
      support in their caregiving relationships, which has been found to be associated
      with PLHIVs' antiretroviral adherence and viral suppression. Data were
      longitudinal (baseline, 6- and 12-month follow-up) from 383 PLHIV who were
      formerly or currently using drugs. Utilizing a longitudinal lagged fixed effects
      structural equation model, we found that never having pain in the past 6 months
      was predictive of increased reciprocity of support. Sub-analyses by care
      relationship type revealed never having pain was a significant predictor of
      greater reciprocity for sexual partner caregiving dyads, but not for kin or
      friend caregiving dyads. Our study emphasizes the importance of pain management
      in quality caregiving relationships characterized by reciprocity, which has
      consistently been found to be associated with stronger, more supportive
      caregiving relationships and better quality of life. Our findings suggest the
      importance of pain management intervention for improving reciprocity between
      vulnerable PLHIVs and their primary caregivers, especially between PLHIVs and
      caregivers who are current or former sexual partners.

PMID- 28451890
TI  - HIV Prevention in Gay Family and House Networks: Fostering Self-Determination and
      Sexual Safety.
AB  - Many gay, bisexual, and transgender (GBT) people of color (POC) join house and/or
      constructed family communities, which serve as support networks composed mostly
      of other non-biologically related GBT/POC. These networks can decrease or
      increase the risk of exposure to HIV via multiple mechanisms (e.g., providing
      informal sexual safety education versus stigmatizing family members with HIV,
      encouraging sexual safety practices versus unsafe escorting, teaching self-care
      versus substance use) but act to support family members in the face of social and
      economic hardship. Researchers interviewed ten members of these social networks
      in the Boston metro area of the US and produced a saturated grounded theory
      analysis to explore the role of gay family/house networks in HIV risk management.
      While network members utilized HIV prevention resources, interviewees described
      how their efficacy was related to the intentions of leadership and strength of
      kinship boundaries within their community, economic opportunities, and
      communication skills. Clinical and research implications are discussed.

PMID- 28451891
TI  - Pilot Randomized Controlled Trial of Acceptance-Based Behavior Therapy to Promote
      HIV Acceptance, HIV Disclosure, and Retention in Medical Care.
AB  - HIV patients who are not retained in medical care risk viral resistance, disease
      progression to AIDS, and mortality. Numerous interventions have been tested to
      improve retention, but they are limited by their resource-intensive approaches
      and lack of focus on new patients, who are at highest risk for drop-out. Data
      show that acceptance and disclosure of HIV status might impact retention, yet
      these variables have not been targeted in previous interventions. In this pilot
      randomized controlled trial, we assessed feasibility, acceptability, and
      preliminary efficacy of a brief, 2-session acceptance based behavior therapy
      (ABBT), relative to treatment-as-usual (TAU), in 34 new-to-care HIV patients.
      ABBT attendance was high and patient feedback was positive. Relative to TAU, ABBT
      had significant positive effects on retention, as well as putative mechanisms of
      action, including experiential avoidance of HIV, willingness to make and actual
      disclosures of HIV status, and perceived social support. Further testing of ABBT
      is warranted. Trial registered at clinicaltrials.gov; Clinical Trial
      #NCT02004457.

PMID- 28451892
TI  - Oral paricalcitol: expanding therapeutic options for pediatric chronic kidney
      disease patients.
AB  - The complex pathophysiology of progressive chronic kidney disease (CKD) and the
      development of mineral and bone disorder, abbreviated as CKD-MBD, is of vital
      importance to a pediatric patient. Paricalcitol, the 19 nor-1,25(OH)2D2 analogue
      was shown to be effective and safe in the treatment of secondary
      hyperparathyroidism (SHPT) in adults almost two decades ago. It also
      significantly improved survival in dialysis patients compared to the standard
      calcitriol. The successful treatment of CKD-MBD in children is essential if they
      are to grow and survive into adulthood. It can be argued that it is more
      important for children with CKD than adults since they have early and prolonged
      disease risk exposure. In this issue of Pediatric Nephrology, Webb et.al. report
      a dual trial of the safety, efficacy, and pharmacokinetics of paricalcitol in
      children aged 10-16 years with moderate but significant efficacy in meeting the
      endpoint of >30% decrease in parathyroid hormone (PTH) levels from baseline with
      minimal adverse events. Much more research needs to be done to expand and develop
      clinical pharmaceutical trials in the use of paricalcitol in children, especially
      in the younger age categories. This current study has done much to open the doors
      for future studies, with the caveat that it has been long coming and much more
      needs to be done to compensate for this delay in the treatment of children with
      CKD-MBD and cardiovascular and renal disease progression.

PMID- 28451894
TI  - Salt, sweat, and unclear? Diaphoresis and hypernatremia in end-stage kidney
      disease: Questions.
AB  - This quiz will discuss two patients with end-stage kidney disease (ESKD) on
      dialysis presenting with diaphoresis and hypernatremia.

PMID- 28451893
TI  - Immunology of idiopathic nephrotic syndrome.
AB  - The pathogenesis of idiopathic nephrotic syndrome (INS) is as yet unknown, but
      several lines of evidence indicate that the immune system may play a crucial
      pathogenic role in non-genetic INS. The most important of these are, first, the
      effectiveness of therapy based on immunosuppression and, second, a vast body of
      data derived both from experimental models and from patient studies that
      implicate T cells and more recently B cells as major players in INS pathogenesis.
      However, recent findings also suggest a direct role of podocytes as drivers of
      the disease process, and the interplay between the glomerulus and the immune
      system is still being elucidated. In this review we provide an overview of
      current knowledge on the role of different components of the immune system in
      determining disease. Advances in our understanding of the pathogenesis of INS may
      help drive new, more tailored therapeutic approaches.

PMID- 28451895
TI  - Salt, sweat, and unclear? Diaphoresis and hypernatremia in end-stage kidney
      disease: Answers.

PMID- 28451896
TI  - Prospective analysis of long-term renal function in survivors of childhood Wilms
      tumor.
AB  - BACKGROUND: Considering the improved outcome, a better understanding of the late
      effects in Wilms tumor survivors (WT-S) is needed. This study was aimed at
      evaluating renal function and determining the prevalence of clinical and
      subclinical renal dysfunction in a cohort of WT-S using a multimodal diagnostic
      approach. METHODS: Thirty-seven WT-S were included in this prospective cross
      sectional single center study. To evaluate renal function, glomerular filtration
      rate (GFR) and urinary protein excretion were assessed. Additionally, kidney
      sonomorphology and blood pressure were analyzed. RESULTS: All examined WT-S (mean
      age 28.7 years, mean follow-up 24.8 years) had been treated with a combination of
      surgery and chemotherapy; 59.5% had received adjuvant radiotherapy. Impaired
      glomerular renal function was detected in a considerable proportion of WT-S, with
      age-adjusted cystatin-based GFR estimation below age norm in 55.9%. A lower
      cystatin-based estimated GFR (eGFR) correlated with longer follow-up time and
      higher irradiation dose. In 5 patients (13.5%) albuminuria was identified.
      Analysis of sonomorphology detected compensatory contralateral renal hypertrophy
      in 83.3% of WT-S. Chronic kidney disease (CKD) >= stage II was present in 55.9%
      of WT-S. Blood pressure measurements revealed arterial hypertension in 15 (40.5%)
      WT-S (newly diagnosed n=10). In 24.3% both CKD >= stage II and arterial
      hypertension were determined. CONCLUSION: Even though WT-S are believed to carry
      a low risk for end-stage renal disease, in this study, a remarkable number of WT
      S presented with previously unidentified subclinical signs of renal function
      impairment and secondary morbidity. Therefore, it is important to continue
      regular follow-up, especially after transition into adulthood.

PMID- 28451897
TI  - Sleeping Paranoia Away? An Actigraphy and Experience-Sampling Study with
      Adolescents.
AB  - Paranoid symptoms co-occur with distress and poor functioning and constitute a
      risk for psychosis and other mental disorders. Poor sleep is known to be
      associated with paranoid symptoms, but the direction of the effect and the
      mediating factors have not been studied thoroughly. In an experience-sampling
      study, 61 adolescents wore an actigraph over eight nights and also rated their
      sleep, symptoms of paranoia, and potentially mediating factors. Shorter sleep
      time and more dreaming predicted paranoid symptoms in multilevel regression
      models. Paranoid symptoms did not significantly predict sleep parameters.
      Positive and negative affect partially mediated the effect of sleep time on
      paranoid symptoms. The effects were small, but encourage further research that
      might then be used to improve the prevention of paranoid symptoms.

PMID- 28451899
TI  - Determination of the complete genomic sequence of Neofusicoccum luteum mitovirus
      1 (NLMV1), a novel mitovirus associated with a phytopathogenic
      Botryosphaeriaceae.
AB  - Neofusicoccum luteum species belongs to the Botryosphaeriaceae family and is
      involved in grapevine wood decay diseases. The present study reports the
      discovery and the molecular characterization of a novel mitovirus infecting this
      fungus. Double-stranded RNAs were purified from cultivated N. luteum and analysed
      by next generation sequencing. Using contigs showing BlastX homology with the RNA
      dependent RNA polymerase (RdRp) gene of various members of the family
      Narnaviridae, a single contig of approximately 1.2 kb was constructed. The
      genomic sequence was completed and phylogenetic analyses indicated that this
      virus represents a new member of the genus Mitovirus, for which the name of
      "Neofusicoccum luteum mitovirus 1" is proposed. The genome is 2,389 nucleotides
      long and, based on the fungal mitochondrial genetic code, it encodes a putative
      protein of 710 amino acids, homologous to the RdRps of members of the
      Narnaviridae family. The neofusicoccum luteus mitovirus 1 (NLMV1) RdRp contains
      the six conserved motifs previously reported for mitoviral RdRps. Our findings
      represent the first evidence that a mycovirus can infect N. luteum, an important
      pathogenic fungus of grapevine.

PMID- 28451898
TI  - Human cytomegalovirus infection dysregulates neural progenitor cell fate by
      disrupting Hes1 rhythm and down-regulating its expression.
AB  - Human cytomegalovirus (HCMV) infection is a leading cause of birth defects,
      primarily affecting the central nervous system and causing its maldevelopment. As
      the essential downstream effector of Notch signaling pathway, Hes1, and its
      dynamic expression, plays an essential role on maintaining neural progenitor
      /stem cells (NPCs) cell fate and fetal brain development. In the present study,
      we reported the first observation of Hes1 oscillatory expression in human NPCs,
      with an approximately 1.5 hour periodicity and a Hes1 protein half-life of about
      17 (17.6 +/- 0.2) minutes. HCMV infection disrupts the Hes1 rhythm and down
      regulates its expression. Furthermore, we discovered that depleting Hes1 protein
      disturbed NPCs cell fate by suppressing NPCs proliferation and neurosphere
      formation, and driving NPCs abnormal differentiation. These results suggested a
      novel mechanism linking disruption of Hes1 rhythm and down-regulation of Hes1
      expression to neurodevelopmental disorders caused by congenital HCMV infection.

PMID- 28451900
TI  - Molecular characterization of yerba mate chlorosis-associated virus, a putative
      cytorhabdovirus infecting yerba mate (Ilex paraguariensis).
AB  - We present the molecular characterization of a new virus infecting yerba mate
      (Ilex paraguariensis St. Hil.) in Argentina. Deep sequencing of diseased yerba
      mate plants showing chlorotic linear patterns, chlorotic rings, and vein
      yellowing resulted in the identification of a new virus resembling plant
      rhabdoviruses in sequence and genome structure. We have determined the complete
      genome sequence of this virus, which is 12,876 nt long. Seven open reading frames
      (ORFs) were identified in the antigenomic orientation of the negative-sense,
      single-stranded viral RNA, in the order 3'-N-P-P3-P4-M-G-L-5'. Phylogenetic
      analysis suggested that the described virus is a new member of the genus
      Cytorhabdovirus, which was supported by the observation of rhabdovirus-like
      particles within the cytoplasm of infected yerba mate cells. The virus has been
      tentatively named "yerba mate chlorosis-associated virus" (YmCaV). The
      availability of the YmCaV genome sequence will contribute to assessing the
      genetic variability of this virus and determining its role in this yerba mate
      disease.

PMID- 28451901
TI  - Genotype-specific real-time PCR combined with high-resolution melting analysis
      for rapid identification of red-spotted grouper nervous necrosis virus.
AB  - A real-time genotype-specific polymerase chain reaction (PCR) assay combined with
      high-resolution melting (HRM) analysis was developed to assess the most common
      genotypes of nervous necrosis viruses or nodaviruses. Nodaviruses are the causal
      agents of viral nervous necrosis infections, which have been wreaking havoc in
      the aquaculture industry worldwide, with fish mortality up to 100%. The four
      different genotypes of nodaviruses correlate with differences in viral
      pathogenicity. Therefore, rational development of effective vaccines and
      diagnostics requires analysis of genetic variation among viruses. The aim of the
      present study was to develop a real-time tetra-primer genotype-specific PCR assay
      for genotype identification. Four primers were utilized for simultaneous
      amplification of nodavirus genotype-specific products in a single closed-tube PCR
      after a reverse-transcription reaction using RNA isolated from fish samples. For
      high-throughput sample analysis, SYBR Green-based real-time PCR was used in
      combination with HRM analysis. The assay was evaluated in terms of specificity
      and sensitivity. The analysis resulted in melting curves that were indicative of
      each genotype. The detection limit when using reference plasmids was 100 ag/uL
      for both genotypes, while the sensitivity of the assays when testing a complex
      mixture was 10 fg/uL for red-spotted grouper nervous necrosis virus (RGNNV) and
      100 fg/uL for striped jack nervous necrosis virus (SJNNV). To test the capability
      of this method under real-world conditions, 58 samples were examined. All samples
      belonged to the RGNNV genotype, which was fully validated. The results were in
      full agreement with genotyping by reference methods. The proposed methodology
      provides a rapid, sensitive, specific, robust and automatable assay for nodavirus
      genotyping, making it a useful tool for diagnosis and screening for
      epidemiological studies.

PMID- 28451902
TI  - Genetic characterization of equid herpesvirus type 1 from cases of abortion in
      Poland.
AB  - Equid herpesvirus type 1 (EHV-1) is a common viral infection associated with
      varied clinical outcomes including respiratory disease, abortion and neurological
      disease. We have characterized EHV-1 sequences (n = 38) obtained from cases of
      equine abortion in Poland between 1999 and 2016, based on sequencing of PCR
      products from open reading frames (ORF) 30 and 68 of the EHV-1 genome. The
      majority (81.6%) of sequences were not classified into any of the previously
      described groups based on the ORF68 sequence. The remaining sequences belonged to
      ORF68 group III (7.9%) or IV (10.5%). A haplotype network analysis did not show
      any obvious structure within networks of local Polish sequences, nor within a
      global network of 215 EHV-1 sequences when these networks were coloured based on
      the geographical origin of viruses or date of detection. Our data suggest that
      ORF68 does not provide a reliable molecular marker for epidemiological studies of
      EHV-1, at least in a global sense. Its usefulness to aid local investigations of
      individual outbreaks remains to be established. All but two Polish EHV-1
      sequences belonged to the ORF30 N752 genotype. The two ORF30 D752 viruses were
      obtained from abortion cases in 2009 and 2010. Hence, abortion cases that
      occurred in Poland between 1999 and 2016 were caused predominantly by EHV-1 with
      the ORF30 N752 genotype, with no indication of an increase in the prevalence of
      the ORF30 D752 variant.

PMID- 28451903
TI  - A single L288I substitution in the fusion protein of bovine parainfluenza virus
      type 3 enhances virus growth in semi-suitable cell lines.
AB  - The bovine parainfluenza virus type 3 BN-CE vaccine strain was obtained by serial
      passage of the BN-1 strain in chicken embryonic fibroblasts (CEF). We previously
      identified a substitution (L288I) in the fusion (F) protein between the two
      strains. To examine the effect of the substitution on CEF adaptation and
      attenuation, we generated a recombinant BN-1 strain with the L288I substitution
      in the F protein (FL288I-EGFP). FL288I-EGFP replicated more efficiently than a
      recombinant BN-1 strain (wt-EGFP) in semi-suitable cell lines, suggesting that
      the L288I substitution was established in the BN-1 strain during the process of
      adaptation in CEF.

PMID- 28451904
TI  - Anxiety sensitivity predicts increased perceived exertion during a 1-mile walk
      test among treatment-seeking smokers.
AB  - Smoking increases risk of early morbidity and mortality, and risk is compounded
      by physical inactivity. Anxiety sensitivity (fear of anxiety-relevant somatic
      sensations) is a cognitive factor that may amplify the subjective experience of
      exertion (effort) during exercise, subsequently resulting in lower engagement in
      physical activity. We examined the effect of anxiety sensitivity on ratings of
      perceived exertion (RPE) and physiological arousal (heart rate) during a bout of
      exercise among low-active treatment-seeking smokers. Adult daily smokers (n =
      157; M age  = 44.9, SD = 11.13; 69.4% female) completed the Rockport 1.0 mile
      submaximal treadmill walk test. RPE and heart rate were assessed during the walk
      test. Multi-level modeling was used to examine the interactive effect of anxiety
      sensitivity * time on RPE and on heart rate at five time points during the walk
      test. There were significant linear and cubic time * anxiety sensitivity effects
      for RPE. High anxiety sensitivity was associated with greater initial increases
      in RPE during the walk test, with stabilized ratings towards the last 5 min,
      whereas low anxiety sensitivity was associated with lower initial increase in RPE
      which stabilized more quickly. The linear time * anxiety sensitivity effect for
      heart rate was not significant. Anxiety sensitivity is associated with increasing
      RPE during moderate-intensity exercise. Persistently rising RPE observed for
      smokers with high anxiety sensitivity may contribute to the negative experience
      of exercise, resulting in early termination of bouts of prolonged activity and/or
      decreased likelihood of future engagement in physical activity.

PMID- 28451906
TI  - Saul Hertz, MD, and the birth of radionuclide therapy.
AB  - The year, 2016, marked the 75th anniversary of Dr. Saul Hertz first using
      radioiodine to treat a patient with thyroid disease. In November of 1936, a
      luncheon was held of the faculty of Harvard Medical School where Karl Compton,
      PhD, president of the Massachusetts Institute of Technology was invited to give a
      presentation entitled "What Physics Can Do for Biology and Medicine." Saul Hertz
      who attended the luncheon spontaneously asked the very pertinent question that
      perhaps changed the course of treatment of thyroid disease, "Could iodine be made
      radioactive artificially?" We review the events leading up to the asking of this
      question, the preclinical investigations by Dr. Hertz and his colleague Arthur
      Roberts prior to the treatment of the first patient and what occurred in the
      years following this landmark event. This commentary seeks to set the record
      straight to the sequence of events leading to the first radioiodine therapy, so
      that those involved can be recognized with due credit.

PMID- 28451908
TI  - Arny Demain.

PMID- 28451907
TI  - On being an honorary member of Arny's army: some musings about fungal
      fermentations, secondary metabolism, and scientific communities.
AB  - This essay is an unabashed celebration of applied microbiology and secondary
      metabolism, and how one scientist-Arnold Demain-has been a spokesman for
      industrial microbiology and biotechnology. There are many reasons for Arny's
      professional success. During his long and distinguished career, Arnold Demain has
      expanded and enriched our understanding of the importance secondary metabolism.
      He has studied topics that ranged from pickles, to pectinolytic enzymes, to
      penicillin. His experimental versatility was conducted under the unifying theme
      of fermentation microbiology. In addition, one of his most positive achievements
      was his ability to bring scientists from different disciplines and national
      backgrounds together and thereby nucleate new collaborations. I am one of many
      people who has benefited from Arny's generous mentoring and speak from the heart
      when I say that industrial microbiology could not have a better representative.
      Arny has been the catalyst for much of that has gone right in my professional
      life and the lives of the many other applied microbiologists who have had the
      good fortune to know him.

PMID- 28451905
TI  - Effects of Altitude/Hypoxia on Single- and Multiple-Sprint Performance: A
      Comprehensive Review.
AB  - Many sport competitions, typically involving the completion of single- (e.g.
      track-and-field or track cycling events) and multiple-sprint exercises (e.g. team
      and racquet sports, cycling races), are staged at terrestrial altitudes ranging
      from 1000 to 2500 m. Our aim was to comprehensively review the current knowledge
      on the responses to either acute or chronic altitude exposure relevant to single
      and multiple sprints. Performance of a single sprint is generally not negatively
      affected by acute exposure to simulated altitude (i.e. normobaric hypoxia)
      because an enhanced anaerobic energy release compensates for the reduced aerobic
      adenosine triphosphate production. Conversely, the reduction in air density in
      terrestrial altitude (i.e. hypobaric hypoxia) leads to an improved sprinting
      performance when aerodynamic drag is a limiting factor. With the repetition of
      maximal efforts, however, repeated-sprint ability is more altered (i.e. with
      earlier and larger performance decrements) at high altitudes (>3000-3600 m or
      inspired fraction of oxygen <14.4-13.3%) compared with either normoxia or low-to
      moderate altitudes (<3000 m or inspired fraction of oxygen >14.4%).
      Traditionally, altitude training camps involve chronic exposure to low-to
      moderate terrestrial altitudes (<3000 m or inspired fraction of oxygen >14.4%)
      for inducing haematological adaptations. However, beneficial effects on sprint
      performance after such altitude interventions are still debated. Recently,
      innovative 'live low-train high' methods, in isolation or in combination with
      hypoxic residence, have emerged with the belief that up-regulated non
      haematological peripheral adaptations may further improve performance of multiple
      sprints compared with similar normoxic interventions.

PMID- 28451909
TI  - Introduction to the Special Issue: "Arnold Demain-Industrial Microbiologist
      Extraordinaire".

PMID- 28451910
TI  - Hypertension Across the Atlantic: A Sprint or a Marathon?

PMID- 28451911
TI  - Effective patient-provider communication about sexual concerns in breast cancer:
      a qualitative study.
AB  - PURPOSE: Breast cancer patients commonly experience sexual concerns, yet rarely
      discuss them with clinicians. The study examined patient and provider experiences
      and preferences related to communication about breast cancer-related sexual
      concerns with the goal of informing intervention development. METHODS: Patient
      data (n = 28) were derived from focus groups and interviews with partnered and
      unpartnered women treated for breast cancer reporting sexual concerns. Provider
      data (n = 11) came from interviews with breast cancer oncologists and nurse
      practitioners. Patient and provider data were analyzed separately using the
      framework method of qualitative analysis. RESULTS: Findings revealed individual
      and institutional barriers to effective communication about sexual concerns and
      highlighted key communication facilitators (e.g., a positive patient-provider
      relationship, patient communication as a driver of provider communication, and
      vice versa). Patients expressed preferences for open, collaborative
      communication; providers expressed preferences for focused intervention targets
      (identifying concerns, offering resources/referrals) and convenient format. A
      model of effective communication of sexual concerns was developed to inform
      communication interventions. CONCLUSIONS: Findings suggest that to improve
      patient-provider communication about sexual concerns, knowledge and skills-based
      interventions that activate patients and that equip providers for effective
      discussions about sexual concerns are needed, as are institutional changes that
      could incentivize such discussions.

PMID- 28451912
TI  - A conceptual framework for patient-reported outcomes in non-muscle invasive
      bladder cancer.
AB  - PURPOSE: Non-muscle invasive bladder cancer (NMIBC) is a chronic condition
      requiring repeated treatment and endoscopic examinations that can be life-long.
      In this context, health-related quality of life (HRQOL) is important to patients
      and managing clinicians, and integral to treatment recommendations for NMIBC. The
      aim of this study was to develop a conceptual framework of patient-reported NMIBC
      symptoms, treatment side effects, and HRQOL impacts from three sources: (1)
      literature, (2) patients and (3) treating clinicians. METHODS: First, we
      undertook a scoping literature review for studies reporting patient-reported
      outcomes associated with NMIBC. Outcomes were extracted and grouped conceptually.
      Then, we conducted semi-structured interviews with patients with NMIBC and
      treating clinicians. Patients were asked about symptoms and HRQOL impacts
      experienced from their NMIBC and treatments. Clinicians were asked about commonly
      reported outcomes, and outcomes they felt were important to assess clinically.
      Interviews were audio recorded, transcribed and content analysed. RESULTS: A
      total of 125 symptom- and functioning-related expressions from 18 studies, 26
      patients and 20 clinicians were coded into three themes and 18 sub-themes.
      Patients commonly reported blood in urine and frequent urination. Clinicians
      considered BCG sepsis and flu-like symptoms important outcomes to assess during
      treatment for NMIBC. CONCLUSION: Our empirically derived conceptual framework
      identifies patient-reported outcomes that are important to people with NMIBC,
      provides the basis for the development of a new NMIBC-specific symptom index, and
      guides the design of a comprehensive PRO assessment plan for clinical practice in
      NMIBC and future clinical trials of treatments for NMIBC.

PMID- 28451913
TI  - EEG microstates during different phases of Transcendental Meditation practice.
AB  - Two phases of Transcendental Meditation (TM)-transcending and undirected
      mentation-were compared to each other and to task-free resting using multichannel
      EEG recorded from 20 TM practitioners. An EEG microstate analysis identified four
      classes of microstates which were labeled A, B, C and D, based on their
      similarity to previously published classes. For each class of microstates, mean
      duration, coverage and occurrence were computed. Resting and transcending
      differed from undirected mentation with decreased prominence of Class A and
      increased prominence of Class D microstates. In addition, transcending showed
      decreased prominence of Class C microstates compared to undirected mentation.
      Based on previous findings on the functional significance of the microstate
      classes, the results indicate an increased reference to reality and decreased
      visualization during resting and transcending compared to undirected mentation.
      Also, our results indicate decreased saliency of internally generated mentations
      during transcending compared to undirected mentation reflecting a more detached
      and less evaluative processing. It is proposed that the continuous cycling
      through these two phases of meditation during a TM session might facilitate and
      train the flexible modulation of the parameters of these microstates of these
      particular classes which are known to be altered in psychiatric disorders. This
      might promote beneficial stabilizing effects for the practitioner of TM.

PMID- 28451914
TI  - Assessment of Anti-vinculin and Anti-cytolethal Distending Toxin B Antibodies in
      Subtypes of Irritable Bowel Syndrome.
AB  - BACKGROUND: Antibodies to cytolethal distending toxin B (CdtB) and vinculin are
      novel biomarkers that rule-in and differentiate irritable bowel syndrome with
      diarrhea (IBS-D) from other causes of diarrhea and healthy controls. AIM: To
      determine whether these antibodies can also diagnose and differentiate other IBS
      subtypes. METHODS: Subjects with IBS-D based on Rome III criteria (n = 2375) were
      recruited from a large-scale multicenter clinical trial (TARGET 3). Healthy
      subjects without gastrointestinal (GI) diseases or symptoms (n = 43) and subjects
      with mixed IBS (IBS-M) (n = 25) or IBS with constipation (IBS-C) (n = 30) were
      recruited from two major medical centers. Plasma levels of anti-CdtB and anti
      vinculin antibodies in all subjects were determined by enzyme-linked
      immunosorbent assay. Optical densities of >=1.68 and >=2.80 were considered
      positive for anti-vinculin and anti-CdtB, respectively. Plasma levels of anti
      CdtB and anti-vinculin antibodies were highest in IBS-D and lowest in IBS-C and
      healthy controls (P < 0.001). Levels in IBS-C subjects were not statistically
      different from controls (P > 0.1). Positivity for anti-CdtB or anti-vinculin
      resulted in a statistically significant negative gradient from IBS-D (58.1%) to
      IBS-M (44.0%), IBS-C (26.7%), and controls (16.3%) (P < 0.001). CONCLUSIONS: Anti
      CdtB and anti-vinculin titers and positivity rates differ in IBS subtypes, with
      higher antibody levels and positivity rates in IBS-D and IBS-M, and lower levels
      in IBS-C subjects that are similar to those in healthy controls. These antibodies
      appear useful in the diagnosis of IBS-M and IBS-D, but not IBS-C. Furthermore,
      these findings suggest that IBS-C is pathophysiologically distinct from subtypes
      with diarrheal components (i.e., IBS-M and IBS-D).

PMID- 28451915
TI  - Obesity, Metabolic Syndrome, and Cardiovascular Risk in Gluten-Free Followers
      Without Celiac Disease in the United States: Results from the National Health and
      Nutrition Examination Survey 2009-2014.
AB  - BACKGROUND: Despite unclear benefits of gluten-free diets (GFD) in the general
      population, gluten-free followers without medical indications are driving the
      market. Few studies have investigated health benefits of GFD in the general
      population. AIMS: To estimate metabolic and cardiovascular disease (CVD) risk
      profiles among gluten-free followers without celiac disease (CD). METHODS: Data
      were obtained from the National Health and Nutrition Examination Survey (NHANES)
      2009-2014. There were 13,523 persons without CD who had GFD information. People
      with known CVD were excluded. We compared gluten-free followers without CD and
      the general population by selective metabolic and CVD risk profiles using survey
      weighted generalized logistic regression. RESULTS: There were 155 gluten-free
      followers without CD and CVD, corresponding to a weighted prevalence of 1.3% (3.2
      million Americans). Gluten-free followers tended to be women and have a smaller
      waist circumference and higher HDL cholesterol. They also had a lower BMI with a
      borderline p value (0.053) and significant self-reported weight loss (-1.33 kg)
      over one year. Moreover, gluten-free followers were more likely to consider their
      weight appropriate. There was no statistical difference by age, smoking,
      hypertension, total cholesterol, triglyceride cholesterol, HbA1c, or fasting
      glucose. Despite a lower probability of having metabolic syndrome (33.0 vs 38.5%)
      and lower 10-year CVD risk score (4.52 vs 5.70%) in gluten-free followers, there
      was no statistical difference. CONCLUSIONS: Although being on a GFD may be
      beneficial in weight management, there was no significant difference in terms of
      prevalence of metabolic syndrome and CVD risk score in gluten-free followers
      without CD.

PMID- 28451916
TI  - Outcomes of Fecal Microbiota Transplantation for Clostridium difficile Infection
      in Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) has recently been
      shown to be a promising therapy for recurrent and refractory Clostridium
      difficile infections (CDI) despite lack of protocol standardization. Patients
      with inflammatory bowel disease (IBD) present a particular challenge to CDI
      therapy as they are reported to have worse clinical outcomes, including higher
      colectomy rates and increased mortality. We aimed to assess the outcomes of FMT
      for recurrent CDI in patients with IBD at our healthcare system. METHODS: We
      constructed a retrospective cohort of all patients who underwent FMT at our
      healthcare system between December 2012 and May 2014. Patients with concurrent
      IBD were identified. We evaluated the differences in demographic and clinical
      characteristics, along with the outcomes to FMT between patients with IBD as
      compared to the general population. RESULTS: Over the study period, 201 patients
      underwent FMT of which 20 patients had concurrent IBD. Patients with IBD were
      younger but did not differ from the general population in terms of CDI risk
      factors or disease severity. The response to FMT and rate of CDI relapse in the
      IBD group were not statistically different compared to the rest of the cohort.
      The overall response rate in the IBD population was 75% at 12 weeks. Of the
      patients who failed FMT 4 of 5 patients had active or untreated IBD. CONCLUSION:
      Fecal microbiota transplantation provides a good alternative treatment option
      with high success rates for recurrent or refractory Clostridium difficile
      infection in patients with well-controlled IBD who fail standard antimicrobial
      therapy.

PMID- 28451917
TI  - Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Apoptosis of Gastric
      Cancer Cells via PTEN/p-AKT Pathway.
AB  - BACKGROUND: Long noncoding RNA (lncRNA) plays critical roles in both tumor
      suppressive and oncogenic pathways in the pathological development and prognosis
      of cancers. AIMS: This study aimed to explore the expression of lncRNA AFAP1-AS1
      and its function in gastric cancer (GC). METHODS: The expression of AFAP1-AS1 was
      detected in GC tissues and GC cells by quantitative real-time reverse
      transcription PCR. A small interfering RNA (siRNA) that targeted AFAP1-AS1 was
      transfected into cells to inhibit the expression of AFAP1-AS1. MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and colony formation
      assay were performed to examine the cell proliferation of SGC7901 cell
      transfected with si-AFAP1-AS1. Cell apoptosis was detected by flow cytometry. The
      protein level of cleaved PARP, Caspase 3, Caspase 9, Caspase 8, Bcl-2, Bax, p
      AKT, total-AKT, and PTEN were detected by Western blot. RESULTS: AFAP1-AS1 was up
      regulated in GC tissues and GC cells. AFAP1-AS1 knockdown suppressed cell
      viability of SGC7901 transfected with si-AFAP1-AS1. The number of apoptotic
      SGC7901 cell transfected with si-AFAP1-AS1 was increased by 3.4-fold comparing to
      that of control. The protein level of cleaved PARP, Caspase 3, and Caspase 9 were
      increased in SGC7901 transfected with si-AFAP1-AS1, as well as the expression of
      Bax. The protein level of Bcl-2 was decreased. AFAP1-AS1 knockdown decreased the
      protein level of p-AKT and increased the expression of PTEN in SGC7901 cells.
      CONCLUSIONS: AFAP1-AS1 was up-regulated in GC cells and regulated the gastric
      cancer cell proliferation and apoptosis via PTEN/p-AKT pathway.

PMID- 28451918
TI  - Risk factors for poor bone health in primary mitochondrial disease.
AB  - INTRODUCTION: Primary mitochondrial disease is caused by either mitochondrial or
      nuclear DNA mutations that impact the function of the mitochondrial respiratory
      chain. Individuals with mitochondrial disorders have comorbid conditions that may
      increase their risk for poor bone health. The objective of this retrospective
      electronic medical record (EMR) review was to examine risk factors for poor bone
      health in children and adults with primary mitochondrial disease. METHODS: Eighty
      individuals with confirmed clinical and genetic diagnoses of primary
      mitochondrial disease at the Children's Hospital of Philadelphia (CHOP) were
      included in this study. Risk factors and bone health outcomes were collected
      systematically, including: anthropometrics (low BMI), risk-conferring co
      morbidities and medications, vitamin D status, nutrition, immobility, fracture
      history, and, where available, dual energy x-ray absorptiometry (DXA) bone
      mineral density (BMD) results. RESULTS: Of patients 73% (n = 58) had at least one
      risk factor and 30% (n = 24) had four or more risk factors for poor bone health.
      The median number of risk factors per participant was 2, with an interquartile
      interval (IQI 0-4). In the subset of the cohort who were known to have sustained
      any lifetime fracture (n = 11), a total of 16 fractures were reported, six of
      which were fragility fractures, indicative of a clinically significant decrease
      in bone strength. CONCLUSIONS: The prevalence of risk factors for poor bone
      health in primary mitochondrial disease is high. As part of supportive care,
      practitioners should address modifiable risk factors to optimize bone health, and
      have a low threshold to evaluate clinical symptoms that could suggest occult
      fragility fracture.

PMID- 28451919
TI  - A novel conditional Sgsh knockout mouse model recapitulates phenotypic and
      neuropathic deficits of Sanfilippo syndrome.
AB  - Mucopolysaccharidosis (MPS) type IIIA, or Sanfilippo syndrome, is a
      neurodegenerative lysosomal storage disorder caused by a deficiency of the
      lysosomal enzyme N-sulfoglucosamine sulfohydrolase (SGSH), involved in the
      catabolism of heparan sulfate. The clinical spectrum is broad and the age of
      symptom onset and the degree of preservation of cognitive and motor functions
      appears greatly influenced by genotype. To explore this further, we generated a
      conditional knockout (Sgsh KO ) mouse model with ubiquitous Sgsh deletion, and
      compared the clinical and pathological phenotype with that of the spontaneous
      Sgsh D31N MPS-IIIA mouse model. Phenotypic deficits were noted in Sgsh KO mice
      prior to Sgsh D31N mice, however these outcomes did not correlate with any shift
      in the time of appearance nor rate of accumulation of primary (heparan sulfate)
      or secondary substrates (GM2/GM3 gangliosides). Other disease lesions (elevations
      in lysosomal integral membrane protein-II expression, reactive astrocytosis and
      appearance of ubiquitin-positive inclusions) were also comparable between
      affected mouse strains. This suggests that gross substrate storage and these
      neuropathological markers are neither primary determinants, nor good
      biomarkers/indicators of symptom generation, confirming similar observations made
      recently in MPS-IIIA patients. The Sgsh KO mouse will be a useful tool for
      elucidation of the neurological basis of disease and assessment of the clinical
      efficacy of new treatments for Sanfilippo syndrome.

PMID- 28451920
TI  - Cortical thickness reductions associate with abnormal resting-state functional
      connectivity in non-neuropsychiatric systemic lupus erythematosus.
AB  - To detect the abnormal cortical thickness and disrupted brain resting-state
      functional connectivity (RSFC) in patients with systemic lupus erythematosus
      (SLE) without neuropsychiatric symptoms (non-NPSLE). Using T1-weighted 3D brain
      structural data, we first determined the regions with abnormal cortical thickness
      in a cohort of 33 adult female non-NPSLE patients. By taking brain regions with
      significantly reduced cortical thickness as the seeds, we calculated their RSFC
      based on the resting-fMRI data and detected the relationship between the RSFC and
      cortical thickness in the non-NPSLE patients. Compared to the controls, the non
      NPSLE patients showed significantly cortical thinning in the left fusiform gyrus
      (FUS.L), left lingual gyrus (LING.L), right lingual gyrus (LING.R) and left
      superior frontal cortex (SFC.L). As for the RSFC, statistical analyses indicated
      that the abnormal cortical thickness in LING.L is associated with increased RSFC
      in the left posterior cingulate cortex (PCC.L), and cortical thinning in SFC.L
      associated with decreased RSFC in left cerebellum 6 (CRBL 6.L) in non-NPSLE
      patients. In addition, in non-NPSLE patients, the decreased cortical thickness in
      LING.L was correlated to the increased RSFC in PCC.L, and decreased cortical
      thickness in SFC.L was correlated to the decreased RSFC in CRBL 6.L. Our findings
      suggest that the cortical abnormalities may affect brain intrinsic connectivity
      in non-NPSLE patients.

PMID- 28451921
TI  - Conflict-related dorsomedial frontal cortex activation during healthy food
      decisions is associated with increased cravings for high-fat foods.
AB  - Previous studies suggest obesity is associated with altered function within the
      insula and dorsomedial frontal cortex (including dorsal anterior cingulate
      cortex; DMFC/dACC), reflecting abnormal reward processing and reduced sensitivity
      to feelings of satiety. Given the proposed roles of DMFC/dACC in monitoring
      response conflict and reward-based decision making, the present study examined
      DMFC/dACC activation, and functional connectivity between the DMFC/dACC and the
      anterior insula (AI), during food-related decision-making. Twenty participants
      recruited from the general population (10 Female) performed a decision task while
      undergoing functional magnetic resonance imaging. They were instructed to "choose
      the healthier option" when simultaneously shown pairs of images of different
      foods. Significant DMFC/dACC activation was observed during food-related decision
      making, and activation levels also positively correlated with self-reported
      cravings for high-fat foods (r = 0.57, p = 0.009) and self-reported desire to eat
      the high-fat foods depicted in the images (r = 0.48, p = 0.032). Negative
      functional connectivity estimates between the right AI and DMFC/dACC were also
      associated with self-reported control over eating (r = -0.50, p = 0.025). These
      results suggest that (1) more intense cravings for unhealthy foods are associated
      with greater response conflict when deciding between healthy and unhealthy food
      options, and (2) lack of eating-related control may involve a reduced influence
      of insula-mediated bodily signals on decision-making. This task may offer a
      neuroimaging-based probe for identifying individuals vulnerable to eating-related
      disorders and should be replicated in clinical populations.

PMID- 28451922
TI  - Adapting Current Strategies to Implement Evidence-Based Prevention Programs for
      Paraprofessional Home Visiting.
AB  - This paper describes a strategy for using evidence-based interventions (EBI) that
      does not require replication and fidelity. Eight parents, identified as positive
      role models, conducted home visits for 101 low-income Latina and Korean pregnant
      women. The home visitors, called mentor mothers (MM), were trained in 10 of the
      practice elements common to 80% of child-focused EBI and how to apply these
      skills to support mothers in obesity prevention, to increase the duration of
      breastfeeding, and to reduce depression. MM reported the content and skills
      utilized on each home visit on mobile phones. Each MM made an average of 153 home
      visits (SD = 173.3), with 28 of these visits being phone contacts. Body mass
      index (BMI) at 6 months was significantly associated with the frequency of MM
      focused on coping with depression (r = .24), but was not related to practice
      elements used by MM. The duration of breastfeeding was significantly related to
      the frequency with which MM focused on the topic of breastfeeding (r = .28) and
      parenting (r = .3), and MM use of attending (r = .24) and relaxation (r = .27).
      Depression was significantly correlated with the frequency of addressing
      depression (r = .27), but not to practice elements. MM did use different
      strategies in the first 150 visits compared to their last 150 visits, reflecting
      data-informed supervision. Evidence synthesized from EBI was used as a novel
      training method, with real-time monitoring and data-informed supervision
      providing evidence of iterative quality improvements in MM behaviors over time,
      as well as a way for linking implementation processes to outcomes.

PMID- 28451923
TI  - Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life
      span-shortening and pro-inflammatory effects of male Sex Peptide.
AB  - Males with null mutation of Sex Peptide (SP) gene were compared to wild-type
      males for the ability to cause physiological changes in females that could be
      reversed by mifepristone. Males from wild-type strains decreased median female
      life span by average -51%. Feeding mifepristone increased life span of these
      females by average +106%. In contrast, SP-null males did not decrease female life
      span, and mifepristone increased median life span of these females by average
      +14%, which was equivalent to the effect of mifepristone in virgin females
      (average +16%). Expression of innate immune response transgenic reporter
      (Drosocin-GFP) was increased in females mated to wild-type males, and this
      expression was reduced by mifepristone. In contrast, SP-null males did not
      increase Drosocin-GFP reporter expression in the female. Similarly, mating
      increased endogenous microbial load, and this effect was reduced or absent in
      females fed mifepristone and in females mated to SP-null males; no loss of
      intestinal barrier integrity was detected using dye-leakage assay. Reduction of
      microbial load by treating adult flies with doxycycline reduced the effects of
      both mating and mifepristone on life span. Finally, mifepristone blocked the
      negative effect on life span caused by transgenic expression of SP in virgin
      females. The data support the conclusion that the majority of the life span
      shortening, immune-suppressive and pro-inflammatory effects of mating are due to
      male SP, and demonstrate that mifepristone acts in females to counteract these
      effects of male SP.

PMID- 28451924
TI  - Microfluidic gut-on-a-chip with three-dimensional villi structure.
AB  - Current in vitro gut models lack physiological relevance, and various approaches
      have been taken to improve current cell culture models. For example, mimicking
      the three-dimensional (3D) tissue structure or fluidic environment has been shown
      to improve the physiological function of gut cells. Here, we incorporated a
      collagen scaffold that mimics the human intestinal villi into a microfluidic
      device, thus providing cells with both 3D tissue structure and fluidic shear. We
      hypothesized that the combined effect of 3D structure and fluidic shear may
      provide cells with adequate stimulus to induce further differentiation and
      improve physiological relevance. The physiological function of our '3D gut chip'
      was assessed by measuring the absorptive permeability of the gut epithelium and
      activity of representative enzymes, as well as morphological evaluation. Our
      results suggest that the combination of fluidic stimulus and 3D structure induces
      further improvement in gut functions. Our work provides insight into the effect
      of different tissue environment on gut cells.

PMID- 28451925
TI  - Syndrome of inappropriate antidiuresis should it be managed by specialised
      endocrinologists?

PMID- 28451926
TI  - The parathyroid leptin axis.

PMID- 28451927
TI  - Another Fatal Outcome with a Biliopancreatic Limb Length of 200 cm with One
      Anastomosis Gastric Bypass.

PMID- 28451928
TI  - A Comparison of the Bariatric Procedures that Are Performed in the Treatment of
      Super Morbid Obesity.
AB  - BACKGROUND: We have experienced numerous cases of super morbid obesity (SMO),
      defined by a BMI of >=50 kg/m2, in which laparoscopic sleeve gastrectomy (LSG)
      was not able to achieve a sufficient weight loss effect. However, the most
      appropriate procedure for the treatment of SMO has not yet been established.
      METHODS: The subjects included 248 successive patients who underwent surgery at
      our hospital from June 2006 to December 2012. We divided the subjects into an SMO
      group (BMI, 50 to <70 kg/m2) and a morbid obesity (MO) group (BMI, 35 to <50
      kg/m2). The subjects underwent LSG, LSG with duodenojejunal bypass (LSG/DJB), or
      laparoscopic Roux-en-Y gastric bypass (LRYGB). The weight loss effects, safety of
      surgery, and metabolic profile changes were compared. RESULTS: Sixty-two subjects
      were classified into the SMO group (25%). The percent excess weight loss (%EWL)
      after LSG among the patients in the SMO group was not significantly different
      from that of patients who underwent other procedures. LSG was associated with a
      significantly lower success rate in terms of weight loss (%EWL >= 50%), in
      comparison to the weight loss at 1 year after LRYGB and at 2 years after LSG/DJB
      and LRYGB. Among the patients in the MO group, the %EWL and the rate of
      successful weight loss did not differ to a statistically significant extent.
      CONCLUSION: This study demonstrated that in patients with SMO, LSG/DJB and LRYGB
      can achieve superior weight loss effects in comparison to LSG.

PMID- 28451929
TI  - Endoscopic Sleeve Gastroplasty for Obesity: a Multicenter Study of 248 Patients
      with 24 Months Follow-Up.
AB  - BACKGROUND: Endoscopic sleeve gastroplasty (ESG) is a technique for managing mild
      to moderately obese patients. We aimed to evaluate the long-term outcomes,
      reproducibility, and predictors of weight response in a large multicenter cohort.
      METHODS: Patients who underwent ESG between January 2013 and December 2015 in
      three centers were retrospectively analyzed. All procedures were performed using
      the Apollo OverStitch device (Apollo Endosurgery, Austin, TX). We performed per
      protocol (PP) and intention-to-treat (ITT) analyses, where patients lost to
      follow-up were considered failures. Multivariable linear and logistic regression
      analyses were performed. RESULTS: We included 248 patients (mean age 44.5 +/- 10
      years, 73% female). Baseline BMI was 37.8 +/- 5.6 kg/m2. At 6 and 24 months, 33
      and 35 patients were lost to follow-up, respectively. At 6 and 24 months, %TBWL
      was 15.2 [95%CI 14.2-16.3] and 18.6 [15.7-21.5], respectively. Weight loss was
      similar between centers at both follow-up intervals. At 24 months, % of patients
      achieving >=10% TBWL was 84.2 and 53% with PP and ITT analyses, respectively. On
      multivariable linear regression analysis, only %TBWL at 6 months strongly
      predicted %TBWL at 24 months (adjusted for age, gender, and baseline BMI, beta =
      1.21, p < 0.001). The odds of achieving >=10%TBWL at 24 months if a patient
      achieved <10%TBWL at 6 months is 0.18 [0.034-0.84]. Five (2%) serious adverse
      events occurred. CONCLUSIONS: ESG effectively induces weight loss up to 24 months
      in moderately obese patients. Failure to achieve adequate weight loss can be
      predicted early, and patients should be offered adjunctive therapies to augment
      it.

PMID- 28451930
TI  - Efficacy of Intragastric Balloon Treatment for Adolescent Obesity.
AB  - BACKGROUND: Several studies conducted in adults suggest that intragastric balloon
      (IGB) is an effective and safe method for weight loss. Although the prevalence of
      obesity in adolescents has increased in recent years, the outcomes of IGB
      treatment in this age group are not known. The aim of this study was to evaluate
      the safety and efficacy of IGB treatment for weight loss in adolescents followed
      up for 6 months. METHODS: This is a retrospective longitudinal study including 27
      adolescents (14-19 years; 23 female). All participants were referred to IGB
      treatment by their attending physician, presented body mass index (BMI) >= 29
      kg/m2 (>p97 BMI/age index) and failed to lose weight in clinical treatments. A
      liquid-filled nonadjustable IGB with a volume of 600 to 700 ml was used for 6
      months. All patients were included in a multidisciplinary program, and adherence
      to this program was evaluated as the number of attended appointments. RESULTS:
      There were no serious complications or deaths. The BMI decreased from 37.04 to
      31.18 kg/m2 (p < 0.0001), body weight decreased from 102.21 to 86.23 kg (p <
      0.0001), and excess weight diminished from 35.18 to 19.12 kg (p < 0.0001). The %
      excess weight loss (%EWL) was 56.19 and % total weight loss (%TWL) 16.35.
      Adherence to the multidisciplinary program correlated directly with %EWL (r =
      0.55; p = 0.0033) and %TWL (r = 0.53; p = 0.0052). CONCLUSION: Endoscopic
      treatment of obesity with an IGB is safe, effective, and may be an emerging
      therapeutic option for adolescents.

PMID- 28451932
TI  - Comparison of Effects of Sleeve Gastrectomy and Gastric Bypass on Lipid Profile
      Parameters in Indian Obese: a Case Matched Analysis.
AB  - BACKGROUND: Obesity is associated with increased mortality due to higher
      cardiovascular risk. A proportion of this risk is attributed to impaired lipid
      profile in the form of high levels of serum total cholesterol, triglycerides, and
      low levels of HDL cholesterol. Both sleeve gastrectomy (LSG) and gastric bypass
      (LGB) have been shown to have favourable effects on lipid profile with some
      variability in improvement. We aimed to study the difference in changes in lipid
      profile after LSG and LGB. METHODS: We performed a retrospective case-matched
      study comparing effects of LSG and LGB on lipid profile of patients who underwent
      bariatric surgery from September 2014 to September 2015. The matching was done
      based on criteria of age and body mass index (BMI). RESULTS: Out of a total of 92
      selected patients, 69 patients underwent LSG and 23 patients underwent LGB. There
      was a significant improvement in serum triglycerides and HDL cholesterol with no
      significant reduction in serum total cholesterol in both LSG and LGB group. There
      was a significant reduction in cardiovascular risk calculated as total
      cholesterol: HDL cholesterol ratio following bariatric surgery (p = 0.002).
      CONCLUSION: Both LSG and LGB have similar effects on lipid profile cardiovascular
      risk attributed to it in Indian obese. Thus, sleeve gastrectomy may be considered
      as effective as a gastric bypass for dyslipidaemia improvement in Indian
      patients.

PMID- 28451931
TI  - Predictive Value of Gut Peptides in T2D Remission: Randomized Controlled Trial
      Comparing Metabolic Gastric Bypass, Sleeve Gastrectomy and Greater Curvature
      Plication.
AB  - BACKGROUND: Our aim was to determine the predictive value of gut hormone changes
      for the improvement of type 2 diabetes (T2D) following metabolic Roux-en-Y
      gastric bypass (mRYGB), sleeve gastrectomy (SG), and greater curvature plication
      (GCP) in a randomized controlled trial. Contradictory results have been obtained
      regarding the role of gastrointestinal hormones (in particular GLP-1) in
      beneficial metabolic bariatric surgery outcomes. METHODS: Forty-five patients
      with T2D (mean BMI 39.4 +/- 1.9 kg/m2) were randomly assigned to mRYGB, SG, or
      GCP. Anthropometric and biochemical parameters, fasting concentrations of PYY,
      ghrelin, glucagon, and area under the curve (AUC) of GLP-1 after a standard meal
      test were determined prior to and at months 1 and 12 after surgery. RESULTS:
      Twelve months after surgery, total weight loss percentage was higher and HbA1c
      lower in the mRYGB group than in the SG and GCP groups (-35.2 +/- 8.1 and 5.1 +/-
      0.6% vs. -27.8 +/- 5.4 and 6.2 +/- 0.8% vs. -20.5 +/- 6.8 and 6.6 +/- 1.3%; p =
      0.007 and p < 0.001, respectively). Moreover, GLP-1 AUC at months 1 and 12 was
      greater and T2D remission was higher in mRYGB (80 vs. 53.3 vs. 20%, p < 0.001).
      Insulin treatment (odds ratio (OR) 0.025, p = 0.018) and the increase in GLP-1
      AUC from baseline to month 1 (OR 1.021, p = 0.013) were associated with T2D
      remission. CONCLUSIONS: mRYGB achieves a superior rate of weight loss and T2D
      remission at month 12. Enhanced GLP-1 secretion 1 month after surgery was a
      determinant of glucose metabolism improvement. Registration number (
      http://www.clinicaltrials.gov ): NCT14104758.

PMID- 28451933
TI  - Long-Term Food Tolerance After Bariatric Surgery: Comparison of Three Different
      Surgical Techniques.
AB  - BACKGROUND: Food tolerance has been related to quality of life after bariatric
      surgery. However, long-term results about this issue are quite limited. The aim
      of this study was to evaluate the long-term food tolerance in obese patients
      submitted to surgery, comparing the results between gastric bypass (GBP), long
      alimentary modified biliopancreatic diversion (MBPD), and long alimentary
      modified duodenal switch (MDS). METHODS: A cross-sectional analytic study was
      performed. Food tolerance was studied with a questionnaire based on subjective
      alimentary satisfaction, tolerance to different foods, and frequency of vomiting
      and regurgitation. A food tolerance score was obtained (1 point being the worst
      possible tolerance and 27 points being a perfect one). Information was obtained
      with a telephone interview. RESULTS: One hundred ninety-six patients submitted to
      bariatric surgery were included. Ninety-nine patients were submitted to GBP, 54
      to MBPD, and 43 to MDS. One hundred and sixty-one patients (82.1%) were not lost
      during a mean follow-up time of 87.9 months. Mean food tolerance score was 24.2.
      Tolerance satisfaction was good or excellent in 73.3% of the patients. Red meat
      was the worst tolerated food, but nearly 80% of the patients could tolerate it
      without any problem. Mean food tolerance score was 24.6, 24.0, and 23.7 for GBP,
      MBPD, and MDS, respectively. There were no significant differences between these
      procedures in food tolerance score, alimentary satisfaction, or frequency of
      vomiting. CONCLUSIONS: Long-term food tolerance after bariatric surgery is good.
      No differences between GBP, MBPD, and MDS were found.

PMID- 28451934
TI  - Defining Disease Activity and Response to Therapy in MS.
AB  - OPINION STATEMENT: Disease activity in multiple sclerosis (MS) has classically
      been defined by the occurrence of new neurological symptoms and the rate of
      relapses. Definition of disease activity has become more refined with the use of
      clinical markers, evaluating ambulation, dexterity, and cognition. Magnetic
      resonance imaging (MRI) has become an important tool in the investigation of
      disease activity. Number of lesions as well as brain atrophy have been used as
      surrogate outcome markers in several clinical trials, for which a reduction in
      these measures is appreciated in most treatment studies. With the increasing
      availability of new medications, the overall goal is to minimize inflammation to
      decrease relapse rate and ultimately prevent long-term disability. The aim of
      this review is to give an overview on commonly used clinical and imaging markers
      to monitor disease activity in MS, with emphasis on their use in clinical
      studies, and to give a recommendation on how to utilize these measures in
      clinical practice for the appropriate assessment of therapeutic response.

PMID- 28451935
TI  - Single nucleotide polymorphisms in genes of dopaminergic pathways are associated
      with bruxism.
AB  - OBJECTIVES: This research aimed to evaluate the frequency of single nucleotide
      polymorphisms (SNPs) in dopaminergic pathway genes (DRD1, DRD2, DRD3, DRD4, DRD5,
      and MAOB) in patients undergoing bruxism treatment and controls. SUBJECTS AND
      METHODS: Patients submitted to bruxism treatment were classified in awake bruxism
      (61 patients), sleep bruxism (26 patients), and awake-sleep bruxism (43
      patients). Control group included 59 patients. Association between circadian
      manifestations of bruxism and SNPs was investigated using Fisher's exact test,
      chi-squared test, and calculating the odds ratios and their respective 95%
      confidence intervals. RESULTS: The G allele of DRD2 rs1800497 SNP was associated
      with a significant risk reduction of awake-sleep bruxism (p = 0.041), while the C
      allele of DRD3 rs6280 SNP was associated with increased risk of sleep bruxism (p
      = 0.02), and the C allele of DRD5 rs6283 SNP was associated with decreased risk
      of awake bruxism (p = 0.01). CONCLUSIONS: To our knowledge, this is the first
      report exploring the contribution of genetic variants in dopaminergic pathways to
      bruxism development, considering all circadian manifestations. Our findings
      indicate a possible genetic influence in the etiology of awake, sleep, and awake
      sleep bruxism. Therefore, further research is needed to increase the current
      understanding of bruxism physiopathology.

PMID- 28451937
TI  - Thin-section CT findings of thoracolithiasis.
AB  - PURPOSE: To review thin-section CT findings of thoracolithiasis. MATERIALS AND
      METHODS: Thirty-three thin-section CT scans of 9 patients with thoracolithiasis
      diagnosed between 2008 and 2016 were reviewed for the location, shape, longest
      diameter, and calcification of each freely mobile nodule (thoracolith) and for
      the presence of coexisting abnormalities. RESULTS: The mean age of 9 patients (5
      women) was 65.8 years (SD 14.9; range 37-83 years). Eight were > 50 years of age.
      Three patients had two thoracoliths, and the remaining 6 patients had one.
      Thoracoliths were in the left (n = 9) or right (n = 3) pleural cavity, with most
      in the lower pleural cavity. Nine thoracoliths were found to be larger at follow
      up. The median diameters of the 12 thoracoliths were 4.9 mm (range 2.1-10.6 mm)
      and 6.2 mm (range 3.6-11.0 mm) on the initial and latest follow-up CT scans,
      respectively. Concomitant old granulomatous disease (n = 6) and diffuse systemic
      sclerosis-related interstitial lung disease (n = 2) were noted. CONCLUSION:
      Thoracolithiasis can manifest as one or two small calcified nodules. It tends to
      occur in the left lower pleural cavity, occur in a patient aged > 50 years, be
      larger on follow-up, and coincide with other diseases.

PMID- 28451936
TI  - Nitrogen fertilizer application affects lodging resistance by altering secondary
      cell wall synthesis in japonica rice (Oryza sativa).
AB  - Stem mechanical strength is an important agricultural quantitative trait that is
      closely related to lodging resistance in rice, which is known to be reduced by
      fertilizer with higher levels of nitrogen. To understand the mechanism that
      regulates stem mechanical strength in response to nitrogen, we analysed stem
      morphology, anatomy, mechanical properties, cell wall components, and expression
      of cell wall-related genes, in two varieties of japonica rice, namely,
      Wuyunjing23 (lodging-resistant variety) and W3668 (lodging-susceptible variety).
      The results showed that higher nitrogen fertilizer increased the lodging index in
      both varieties due to a reduction in breaking strength and bending stress, and
      these changes were larger in W3668. Cellulose content decreased slightly under
      higher nitrogen fertilizer, whereas lignin content reduced remarkably.
      Histochemical staining revealed that high nitrogen application decreased lignin
      deposition in the secondary cell wall of the sclerenchyma cells and vascular
      bundle cells compared with the low nitrogen treatments, while it did not alter
      the pattern of cellulose deposition in these cells in both Wuyunjing23 and W3668.
      In addition, the expression of the genes involved in lignin biosynthesis, OsPAL,
      OsCoMT, Os4CL3, OsCCR, OsCAD2, OsCAD7, OsCesA4, and OsCesA7, were also down
      regulated under higher nitrogen conditions at the early stage of culm growth.
      These results suggest that the genes involved in lignin biosynthesis are down
      regulated by higher nitrogen fertilizer, which causes lignin deficiency in the
      secondary cell walls and the weakening of mechanical tissue structure.
      Subsequently, this results in these internodes with reduced mechanical strength
      and poor lodging resistance.

PMID- 28451938
TI  - Quantitative accuracy of computed tomography perfusion under low-dose conditions,
      measured using a hollow-fiber phantom.
AB  - PURPOSE: The purpose of this study was to investigate the quantitative accuracy
      under low-dose conditions on computed tomography (CT) perfusion using a hollow
      fiber phantom that had the theoretical absolute values of perfusion indices.
      MATERIALS AND METHODS: Our phantom comprised two components, i.e., a hollow-fiber
      hemodialyzer to pump the diluted contrast material and a surrounding syringe
      shaped X-ray-absorbing body to simulate the absorption of X-rays by a brain and
      cranium. We performed CTP scans on the phantom under various dose conditions
      ranging from 20 to 140 mA using a 64-row CT scanner, measuring experimental
      cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT),
      and time to peak (TTP) values using a deconvolution algorithm. RESULTS: The
      theoretical value of the CBV was within the 95% confidence interval of CBV values
      measured under 80 mA. The CBV measured under low-dose settings and all CBF values
      measured were smaller than the theoretically calculated ones, and all MTT values
      measured were larger. All measured values of the CBV, CBF, MTT, and TTP decreased
      with an increase in image noise under lower dose conditions. CONCLUSION: It is
      difficult to define a low-dose limit in clinical scan conditions because of the
      complex characteristics of perfusion indices.

PMID- 28451939
TI  - Robot-assisted laparoscopic Y-V plasty in 12 patients with refractory bladder
      neck contracture.
AB  - We present preliminary results of a case series on refractory bladder neck
      contracture (BNC) treated with robot-assisted laparoscopic Y-V plasty (RAYV).
      Between 01/2013 and 02/2016, 12 consecutive adult male patients underwent RAYV in
      our hospital. BNC developed after transurethral procedures (n = 9), simple
      prostatectomy (n = 2) and HIFU therapy of the prostate (n = 1). Each patient had
      had multiple unsuccessful previous endoscopic treatments. All RAYV procedures
      were performed using a transperitoneal six-port approach (four-arm robotic
      setting). There were no intraoperative or major postoperative complications.
      During a median follow-up of 23.2 months two cases of refractory BNC were
      observed. In both cases a postoperative International Prostate Symptom Score
      (IPSS) of 20 and 25 was reported, respectively. In contrast, amongst the patients
      without evidence of refractory BNC the median IPSS was 6.5 reflecting an only
      mildly impaired voiding function in most cases, thus, suggesting a treatment
      success in 83.3% of patients. To the best of our knowledge, this is the first
      report on RAYV for refractory BNC. In our series RAYV was feasible in all
      patients, and only two cases of refractory BNC were reported during a median
      follow-up of almost 2 years. At the same time, no intraoperative or major
      postoperative complications were observed. More clinical data with a longer
      follow-up are needed in this promising field to reveal the actual efficacy and
      relevance of RAYV.

PMID- 28451940
TI  - Unstructured Socializing with Peers and Delinquent Behavior: A Genetically
      Informed Analysis.
AB  - A large body of research finds that unstructured socializing with peers is
      positively associated with delinquency during adolescence. Yet, existing research
      has not ruled out the potential for confounding due to genetic factors and
      factors that can be traced to environments shared between siblings. To fill this
      void, the current study examines whether the association between unstructured
      socializing with peers and delinquent behavior remains when accounting for
      genetic factors, shared environmental influences, and a variety of non-shared
      environmental covariates. We do so by using data from the twin subsample of the
      National Longitudinal Study of Adolescent to Adult Health (n = 1200 at wave 1 and
      1103 at wave 2; 51% male; mean age at wave 1 = 15.63). Results from both cross
      sectional and lagged models indicate the association between unstructured
      socializing with peers and delinquent behavior remains when controlling for both
      genetic and environmental influences. Supplementary analyses examining the
      association under different specifications offer additional, albeit qualified,
      evidence supportive of this finding. The study concludes with a discussion
      highlighting the importance of limiting free time with friends in the absence of
      authority figures as a strategy for reducing delinquency during adolescence.

PMID- 28451941
TI  - Peer Exclusion During the Pubertal Transition: The Role of Social Competence.
AB  - For some youth, early puberty is accompanied by peer exclusion. Yet early
      developers may experience less peer exclusion if they have social competence,
      which would bolster their ability to develop and maintain positive relationships
      with their peers. Accordingly, the present study tests whether pubertal timing
      and tempo predicts decrements in children's social competence and whether
      decrements in social competence account for associations between puberty (timing
      and tempo) and peer exclusion over time. Longitudinal data were drawn from 1364
      families (48% female; 76% White; M = 9.32 years, SD = .48, at Wave 3) who
      participated in Waves 3-5 (i.e., grades 4-6) of Phase III of the NICHD-SECCYD.
      The results from latent growth curve models indicated that earlier pubertal
      timing and more rapid pubertal tempo among girls were associated with high
      initial levels of peer exclusion. Moreover, mediation analyses revealed that
      early developers' susceptibility to peer exclusion was associated with their
      initial level of social competence. In boys, pubertal timing and tempo were not
      directly associated with peer exclusion; instead, indirect effects of pubertal
      timing on peer exclusion (intercept, slope) occurred through initial levels of
      social competence. On average, early developers' who had low levels of social
      competence also had high initial levels of peer exclusion but experienced
      decrements in peer exclusion over time. The association between the intercepts
      for puberty and peer exclusion and the slopes for social competence and peer
      exclusion were stronger for boys than girls. Overall, our findings suggest that
      early developers' susceptibility to and experiences of peer exclusion are
      associated with their development of social competence.

PMID- 28451943
TI  - 10th National Congress of the Italian Society for the Study of Eating Disorders
      (SISDCA) : "The Clinical Competence in the treatment of Eating Disorders &
      Obesity (ED&O)" Rome, 9-11 March 2017.

PMID- 28451942
TI  - The measuring of substantia nigra hyperechogenicity in an Italian cohort of
      Parkinson disease patients: a case/control study (NOBIS Study).
AB  - Transcranial sonography (TCS) shows an increased echogenic area of the substantia
      nigra (SN) in patients with Parkinson disease (PD). It has been increasingly used
      in the diagnosis of PD and its differentiation from atypical parkinsonian
      syndromes. Here, we studied the diagnostic accuracy of SN TCS in Italian
      patients. In this blinded cross-sectional study (NOBIS study), two expert neuro
      sonologists performed TCS in 25 PD patients and 29 age- and sex-matched controls.
      The study participants were completely hidden to the TCS investigators using
      large drapery. One month later, the SN TCS recordings were re-read by the initial
      investigator, and cross-read by the second reader. Diagnostic accuracy was
      estimated on the first reading, intra-reader reliability on re-reading, and inter
      reader reliability on cross-readings. The mean SN echogenic area was larger in
      the patients (0.24 cm2) than in the controls (0.15 cm2; Mann-Whitney test, p <
      0.001). SN measures did not differ between right and left, or between ipsilateral
      and contralateral to the clinically more affected side. There was no correlation
      between SN echogenicity and PD severity or duration. High intra-reader
      (concordance correlation coefficient 0.93) and inter-reader (0.98) agreement of
      SN measurements was found. The diagnostic accuracy for the detection of PD was
      high (area under receiver-operating characteristic curve 0.91; 95% CI 0.83-1.00)
      with an optimum cut-off value for SN echogenic area of 0.18 cm2 with the device
      used here (specificity 0.83-0.90; sensitivity 0.72-0.92). This study supports the
      use of SN TCS in the diagnostic workup of PD if performed by trained readers.

PMID- 28451944
TI  - Characterization of Colombian serotype 1 avian paramyxoviruses, 2008-2010.
AB  - Newcastle disease (ND) still remains one of the most important diseases affecting
      domestic poultry in Colombia. Here, for the first time, we report on the
      molecular characterization of 12 virulent and 12 avirulent or lentogenic avian
      paramyxovirus type 1 (APMV-1) strains that were isolated from commercial,
      backyard, and game poultry in Colombia from 2008 to 2010. The 12 virulent
      isolates had a fusion (F) protein cleavage site with basic amino acids at
      positions 113, 115, and 116 and a phenylalanine at position 117 (112RRQKR*F117),
      characteristic of virulent strains. The remaining 12 isolates had the F protein
      cleavage sites 112GKQGR*L117 or 112GRQGR*L117 typical of avirulent or lentogenic
      APMV-1 strains. Phylogenetic analysis of full-length F genes of all isolates was
      performed, and based on the recently proposed criteria for classification of APMV
      1 strains, the 24 Colombian isolates were found to belong to class II viruses and
      clustered into four different genotypes. Ten virulent isolates clustered with
      genotype VII (sub-genotype VIId), seven lentogenic strains within genotype II,
      five lentogenic strains with genotype I (sub-genotype Ia), and two virulent
      isolates within genotype XII. Our data provide essential information on the
      genetic diversity of AMPV-1 isolates circulating in Colombia.

PMID- 28451946
TI  - Using phenotype microarrays in the assessment of the antibiotic susceptibility
      profile of bacteria isolated from wastewater in on-site treatment facilities.
AB  - The scope of the study was to apply Phenotype Biolog MicroArray (PM) technology
      to test the antibiotic sensitivity of the bacterial strains isolated from on-site
      wastewater treatment facilities. In the first step of the study, the percentage
      values of resistant bacteria from total heterotrophic bacteria growing on solid
      media supplemented with various antibiotics were determined. In the untreated
      wastewater, the average shares of kanamycin-, streptomycin-, and tetracycline
      resistant bacteria were 53, 56, and 42%, respectively. Meanwhile, the shares of
      kanamycin-, streptomycin-, and tetracycline-resistant bacteria in the treated
      wastewater were 39, 33, and 29%, respectively. To evaluate the antibiotic
      susceptibility of the bacteria present in the wastewater, using the phenotype
      microarrays (PMs), the most common isolates from the treated wastewater were
      chosen: Serratia marcescens ss marcescens, Pseudomonas fluorescens,
      Stenotrophomonas maltophilia, Stenotrophomonas rhizophila, Microbacterium
      flavescens, Alcaligenes faecalis ss faecalis, Flavobacterium hydatis, Variovorax
      paradoxus, Acinetobacter johnsonii, and Aeromonas bestiarum. The strains were
      classified as multi-antibiotic-resistant bacteria. Most of them were resistant to
      more than 30 antibiotics from various chemical classes. Phenotype microarrays
      could be successfully used as an additional tool for evaluation of the multi
      antibiotic resistance of environmental bacteria and in preliminary determination
      of the range of inhibition concentration.

PMID- 28451945
TI  - Herpesviral capture of immunomodulatory host genes.
AB  - Herpesviruses have acquired numerous genes from their hosts. Although these
      homologs are not essential for viral replication, they often have important
      immunomodulatory functions that ensure viral persistence in the host. Some of
      these viral molecules are called virokines as they mimic cellular cytokines of
      their host such as interleukin-10 (cIL-10). In recent years, many viral homologs
      of IL-10 (vIL-10s) have been discovered in the genome of members of the order
      Herpesvirales. For some, gene and protein structure as well as biological
      activity and potential use in the clinical context have been explored. Besides
      virokines, herpesviruses have also captured genes encoding membrane-bound host
      immunomodulatory proteins such as major histocompatibility complex (MHC)
      molecules. These viral MHC mimics also retain many of the functions of the
      cellular genes, in particular directly or indirectly modulating the activity of
      natural killer cells. The mechanisms underlying capture of cellular genes by
      large DNA viruses are still enigmatic. In this review, we provide an update of
      the advances in the field of herpesviral gene piracy and discuss possible
      scenarios that could explain how the gene transfer from host to viral genome was
      achieved.

PMID- 28451947
TI  - Continuity and Change in, and Child Predictors of, Caregiver Reported Anxiety
      Symptoms in Young People with Autism Spectrum Disorder: A Follow-Up Study.
AB  - Little is known about continuity, change and predictors of anxiety in ASD. This
      follow-up study investigated changes in caregiver-reported anxiety in 54 non
      referred youth with ASD after 10-19 months. Earlier child predictors of later
      anxiety were also examined. Anxiety scores were generally stable. Time 1 ASD
      repetitive behavior symptoms, but not social/communication symptoms, predicted
      Time 2 total anxiety scores, over and above child age, gender and adaptive
      functioning scores, but this predictive relationship was fully mitigated by Time
      1 anxiety scores when these were included as a covariate in the regression model.
      Exploring bi-directionality between autism and anxiety symptomatology, Time 1
      anxiety scores did not predict Time 2 ASD symptoms. Preliminary clinical
      implications and possible future directions are discussed.

PMID- 28451948
TI  - A Survey of Information Source Preferences of Parents of Individuals with Autism
      Spectrum Disorder.
AB  - For parents of children with an Autism spectrum disorder (ASD), high quality,
      easily accessible information and a strong peer network can be the key to raising
      a happy, healthy child, and maintaining family well-being and emotional
      resilience. This article reports the findings of an anonymous survey examining
      the information source preferences for 935 parents of individuals with ASDs in
      North Carolina. Data indicates that parents show similar information seeking
      patterns across the age spectrum, that availability of information (as indicated
      by overall information source selection) decrease as children age. It also shows
      that parents rely heavily on local sources of information, preferring them to
      nonlocal sources (such as the internet) for many types of information.

PMID- 28451949
TI  - Interaction Between the Haptoglobin Genotype and Vitamin E on Cardiovascular
      Disease in Diabetes.
AB  - PURPOSE OF REVIEW: Despite compelling evidence regarding the importance of
      oxidant stress in the development of vascular complications and observational
      studies suggesting that vitamin E may be protective from these complications,
      multiple clinical trials have failed to show benefit from vitamin E
      supplementation in the prevention of vascular complications in diabetes. One
      possible explanation for this failure of vitamin E may have been inappropriate
      patient selection. This review seeks to provide the clinical evidence and
      mechanistic basis for why a subset of individuals defined by their haptoglobin
      (Hp) genotype may derive cardiovascular protection by vitamin E supplementation.
      RECENT FINDINGS: Clinical trial data from the HOPE, ICARE, and WHS studies is
      presented showing a pharmacogenomic interaction between the Hp genotype and
      vitamin E on the development of CVD. Specifically, in individuals with diabetes
      and the Hp2-2 genotype, vitamin E has been shown to be associated with an
      approximately 35% reduction in CVD. Cardioprotection by vitamin E in individuals
      with the Hp2-2 genotype appears to be mediated in part by an improvement in HDL
      functionality as demonstrated in three independent trials in both type 1 diabetes
      and type 2 diabetes. Vitamin E may provide benefit in reducing CVD in Hp2-2
      individuals with diabetes. However, in order for this pharmacogenomic algorithm
      to be accepted as a standard of care and used clinically, an additional large
      prospective study will need to be performed.

PMID- 28451951
TI  - Gastrointestinal mantle cell lymphoma with isolated mass and multiple
      lymphomatous polyposis: report of two cases.
AB  - We herein report two patients with mantle cell lymphoma (MCL), who had isolated
      mass and multiple lymphomatous polyposis (MLP) in the gastrointestinal tract. In
      case 1, esophagogastroduodenoscopy revealed a protruding mass in the duodenum and
      double-balloon endoscopy disclosed numerous polypoid lesions in the ileum. Case 2
      had polyposis in the duodenum and a large mass-forming lesion in the ascending
      colon. Based on the histologic and immunohistochemical findings of the biopsy
      specimens, the diagnosis of MCL was made in both patients. A combination of
      isolated mass and MLP is considered as characteristic endoscopic findings of
      intestinal lesions of MCL.

PMID- 28451952
TI  - A Systematic Review of the Treat and Extend Treatment Regimen with Anti-VEGF
      Agents for Neovascular Age-Related Macular Degeneration.
AB  - Despite significant progress in retaining vision for neovascular age-related
      macular degeneration patients in the era of treatment with intravitreal anti-VEGF
      agents, there is no universally accepted treatment regimen that defines the
      frequency of treatment needed to achieve the optimal visual outcomes while
      simultaneously balancing the burden of long-term, frequent and high-cost
      treatment. Treat and extend has recently and consistently been used by retina
      specialists to minimise the financial and psychological costs of the need for
      frequent treatment with anti-VEGF injections. This is a systematic review that
      presents evidence from clinical trials and the real world on the utilisation of
      treat and extend with anti-VEGF intravitreal injections in neovascular age
      related macular degeneration, and discusses the experience gained thus far from
      the utilisation of such regimens to preserve vision when treating patients over
      the long-term.

PMID- 28451953
TI  - Observing Proton Transfer Reactions Inside the MALDI Plume: Experimental and
      Theoretical Insight into MALDI Gas-Phase Reactions.
AB  - We evaluated the contribution of gas-phase in-plume proton transfer reactions to
      the formation of protonated and deprotonated molecules in the MALDI process. A
      split sample holder was used to separately deposit two different samples, which
      avoids any mixing during sample preparation. The two samples were brought very
      close to each other and desorbed/ionized by the same laser pulse. By using a
      combination of deuterated and non-deuterated matrices, it was possible to observe
      exclusively in-plume proton transfer processes. The hydrogen/deuterium exchange
      (HDX) kinetics were evaluated by varying the delayed extraction (DE) time,
      allowing the desorbed ions and neutrals to interact inside the plume for a
      variable period of time before being extracted and detected. Quantum mechanical
      calculations showed that the HDX energy barriers are relatively low for such
      reactions, corroborating the importance of gas-phase proton transfer in the MALDI
      plume. The experimental results, supported by theoretical simulations, confirm
      that the plume is a very reactive environment, where HDX reactions could be
      observed from 0 ns up to 400 ns after the laser pulse. These results could be
      used to evaluate the relevance of previously proposed (and partially conflicting)
      ionization models for MALDI. Graphical Abstract ?.

PMID- 28451950
TI  - The Role and Potential Therapeutic Implications of the Fibroblast Growth Factors
      in Energy Balance and Type 2 Diabetes.
AB  - PURPOSE OF REVIEW: Obesity and its associated metabolic diseases have reached
      epidemic proportions worldwide, reducing life expectancy and quality of life.
      Several drugs have been tested to treat these diseases but many of them have
      damaging side effects. Consequently, there is an urgent need to develop more
      effective therapies. Recently, endocrine fibroblast growth factors (FGFs) have
      become attractive targets in the treatment of metabolic diseases. This review
      summarizes their most important functions as well as FGF-based therapies for the
      treatment of obesity and type 2 diabetes (T2D). RECENT FINDINGS: Recent studies
      demonstrate that circulating levels of FGF19 are reduced in obesity. In fact,
      exogenous FGF19 administration is associated with a reduction in food intake as
      well as with improvements in glycaemia. In contrast, FGF21 levels are elevated in
      subjects with abdominal obesity, insulin resistance and T2D, probably
      representing a compensatory response. Additionally, elevated levels of
      circulating FGF23 in individuals with obesity and T2D are reported in most
      clinical studies. Finally, increased FGF1 levels in obese patients associated
      with adipogenesis have been described. FGFs constitute important molecules in the
      treatment of metabolic diseases due to their beneficial effects on glucose and
      lipid metabolism. Among all members, FGF19 and FGF21 have demonstrated the
      ability to improve glucose, lipid and energy homeostasis, along with FGF1, which
      was recently discovered to have beneficial effects on metabolic homeostasis.
      Additionally, FGF23 may also play a role in insulin resistance or energy
      homeostasis beyond mineral metabolism control. These results highlight the
      relevant use of FGFs as potential biomarkers for the early diagnosis of metabolic
      diseases. In this regard, notable progress has been made in the development of
      FGF-based therapies and different approaches are being tested in different
      clinical trials. However, further studies are needed to determine their potential
      therapeutic use in the treatment of obesity and obesity-related comorbidities.

PMID- 28451954
TI  - Incidental findings in cardiac magnetic resonance imaging: superiority of bSSFP
      over T1w-HASTE for extra-cardiac findings assessment.
AB  - Incidental findings are frequent in radiological examinations and may have an
      impact on further patient management. The aim of this retrospective study was to
      analyze, which of two thoracic scout sequences is more suitable for detecting
      incidental extra-cardiac findings at cardiac magnetic resonance imaging (CMRI)
      with stress perfusion. During a 14-month period clinically indicated stress
      perfusion CMRI was performed in 97 consecutive patients. For anatomical
      orientation ECG-triggered (electrocardiography) T1w-Half-fourier acquisition
      single-shot turbo spin-echo (HASTE) and balanced steady state free precession
      (bSSFP) sequences were performed for planning the standard cardiac sequences. Two
      radiologists independently studied incidental extra-cardiac findings with both
      sequences and rated the diagnostic confidence of the sequences for this
      assessment using a multinomial model. Furthermore, the interobserver agreement
      between the observers was assessed by weighted kappa statistics. Eight patients
      without incidental findings were excluded. In the other 89 patients a total of
      153 incidental extra-cardiac findings were observed. Overall, 47.1% of findings
      were seen with better diagnostic confidence at bSSFP as opposed to 20.6% at T1w
      HASTE. 32.4% of findings were equally well seen with both sequences. Consequently
      the bSSFP sequence was significantly better in terms of diagnostic confidence for
      detecting the majority of extra-cardiac incidental findings (P < 0.01), whereas a
      minority of findings was better visible by the HASTE sequence. The weighted kappa
      statistics was 0.85, indicating good interobserver agreement. Compared with T1w
      HASTE, the bSSFP sequence improved the visibility of incidental extra-cardiac
      findings at stress perfusion CMRI. While all findings were seen on both
      sequences, bSSFP resulted in improved diagnostic confidence, and the T1w-HASTE
      sequence provided complementary diagnostic information in only a minority of
      patients.

PMID- 28451955
TI  - Evaluation of Brown Midrib Sorghum Mutants as a Potential Biomass Feedstock for
      2,3-Butanediol Biosynthesis.
AB  - Three sorghum backgrounds [Atlas, Early Hegari (EH), and Kansas Collier (KC)] and
      two bmr mutants (bmr6 and bmr12) of each line were evaluated and compared for
      grain and biomass yield, biomass composition, and 2,3-butanediol production from
      biomass. The data showed that the bmr6 mutation in EH background led to a
      significant decrease in stover yield and increase in grain yield, whereas the
      stover yield was increased by 64% without affecting grain yield in KC background.
      The bmr mutants had 10 to 25% and 2 to 9% less lignin and structural carbohydrate
      contents, respectively, and 24 to 93% more non-structural sugars than their
      parents in all sorghum lines, except EH bmr12. The total fermentable sugars
      released were 22 to 36% more in bmr mutants than in parents for Atlas and KC, but
      not for EH. The bmr6 mutation in KC background produced the most promising
      feedstock, among the evaluated bmr mutants, for 2,3-butanediol production without
      affecting grain yield, followed by KC bmr12 and Atlas bmr6, but the bmr mutation
      had an adverse effect in EH background. This indicated that the genetic
      background of the parent line and type of bmr mutation significantly affect the
      biomass quality as a feedstock for biochemical production.

PMID- 28451956
TI  - Therapeutic alliance and treatment outcome in psychodynamic psychotherapy of
      depressed breast cancer patients: the same old story or different from other
      populations?
AB  - BACKGROUND: A good therapeutic alliance is associated with better treatment
      outcomes in diverse types of psychotherapy and patient populations, but little is
      known about therapeutic alliance in psychotherapies with cancer patients. This
      study examines the association of therapeutic alliance and treatment outcome in
      short term psychodynamic psychotherapy (STPP) for breast cancer patients.
      METHODS: Within a randomized controlled trial, 47 completers of STPP could be
      included in the analyses. The therapeutic alliance was assessed by patients and
      therapists at treatment termination with the Helping Alliance Questionnaire.
      Outcome was defined as no diagnosis of depression assessed with Structured
      Clinical Interview for DSM-IV (SCID-I) and a reduction of the HADS-depression
      score by at least two points at treatment termination. RESULTS: Patients'
      alliance ratings were significantly associated with outcome (r = 0.46, p =
      0.015), while, in contrast to findings in non-cancer populations, therapists'
      ratings were unrelated. There was no association between patients' and
      therapists' ratings of therapeutic alliance. Especially success and working
      related aspects of patients' alliance scores were associated with outcome.
      Patients' and therapists' alliance scores were unrelated to any of their baseline
      characteristics, therapist characteristic or treatment variables. CONCLUSION: We
      conclude that therapists should regularly assess the quality of patients'
      perceived therapeutic alliance in the course of psychotherapy with breast cancer
      patients to improve psychotherapy outcome. The breast cancer patients'
      perspective should be actively inquired and considered throughout treatment by
      therapists. Possible discrepancies between both judgements can be addressed in
      treatment.

PMID- 28451957
TI  - Assessment of indoor and outdoor particulate air pollution at an urban background
      site in Iran.
AB  - The relationship between indoor and outdoor particulate air pollution was
      investigated at an urban background site on the Payambar Azam Campus of
      Mazandaran University of Medical Sciences in Sari, Northern Iran. The
      concentration of particulate matter sized with a diameter less than 1 MUm
      (PM1.0), 2.5 MUm (PM2.5), and 10 MUm (PM10) was evaluated at 5 outdoor and 12
      indoor locations. Indoor sites included classrooms, corridors, and office sites
      in four university buildings. Outdoor PM concentrations were characterized at
      five locations around the university campus. Indoor and outdoor PM measurements
      (1-min resolution) were conducted in parallel during weekday mornings and
      afternoons. No difference found between indoor PM10 (50.1 +/- 32.1 MUg/m3) and
      outdoor PM10 concentrations (46.5 +/- 26.0 MUg/m3), indoor PM2.5 (22.6 +/- 17.4
      MUg/m3) and outdoor PM2.5 concentration (22.2 +/- 15.4 MUg/m3), or indoor PM1.0
      (14.5 +/- 13.4 MUg/m3) and outdoor mean PM1.0 concentrations (14.2 +/- 12.3
      MUg/m3). Despite these similar concentrations, no correlations were found between
      outdoor and indoor PM levels. The present findings are not only of importance for
      the potential health effects of particulate air pollution on people who spend
      their daytime over a period of several hours in closed and confined spaces
      located at a university campus but also can inform regulatory about the
      improvement of indoor air quality, especially in developing countries.

PMID- 28451958
TI  - Residue and intake risk assessment of prothioconazole and its metabolite
      prothioconazole-desthio in wheat field.
AB  - In the environment, plants and animals in vivo, pesticides can be degraded or
      metabolized to form transformation products (TPs) or metabolites, which are even
      more toxic than parent pesticides. Hence, it was necessary to evaluate residue
      and risk of pesticides and their TPs (or metabolites). Here, a rapid, simple, and
      reliable method using QuEChERS and LC-MS/MS had been developed for simultaneous
      analysis of prothioconazole and its toxic metabolite, prothioconazole-desthio, in
      soil, wheat plant, straw, and grain. The average recoveries of prothioconazole
      and prothioconazole-desthio in four matrices ranged from 86 to 108% with relative
      standard deviations (RSDs) of 0.53-11.87% at three spiking levels. The method was
      successfully applied to investigate the dissipation and terminal residues of the
      two compounds in wheat field. It was shown that prothioconazole was rapidly
      degraded to prothioconazole-desthio, with half-lives below 5.82 days.
      Prothioconazole-desthio was slowly dissipated in soil and plant. The terminal
      residues of prothioconazole in wheat grain with a pre-harvest interval (PHI) of
      21 or 28 days were below the maximum residue limits (MRLs) (0.1 mg/kg, Codex
      Alimentarius Commission (CAC)). We also evaluated the intake risk of
      prothioconazole-desthio residues in wheat grain in China. For long-term intake
      assessment, the hazard quotients (HQ) ranged from 1.30 to 5.95%. For short-term
      intake assessment, the acute hazard indexes (aHI) ranged from 1.94 to 18.2%. It
      indicated that the intake risk of prothioconazole-desthio in wheat consumption
      was acceptable. Thus, the prothioconazole application on wheat with the
      scientific practices would not pose public health risk.

PMID- 28451959
TI  - Impact of mining and forest regeneration on small mammal biodiversity in the
      Western Region of Ghana.
AB  - Much of the terrestrial biodiversity in sub-Saharan Africa is supported by
      tropical rainforest. Natural resource development, particularly surface mining in
      the rainforest, poses great risks to the region's rich and endemic biodiversity.
      Here, we assessed the impact of surface mining and the success of forest
      rehabilitation on small mammal diversity in the Western Region of Ghana. We
      surveyed small mammals in the project area and two adjoining forest reserves
      (control sites) before the mining operation and 10 years after mine closure and
      forest rehabilitation (topsoil replacement and revegetation). The forest reserves
      recorded higher species abundance than the mining areas. Majority of the species
      captured in the forest reserves, including Hylomyscus alleni, Praomys tullbergi,
      Malacomys cansdalei, and Hybomys trivirgatus, are forest obligate species. Only
      one individual each of H. alleni and P. tullbergi was captured in the naturally
      regenerated areas (core areas of mining activities that were allowed to
      revegetate naturally), while 32 individuals belonging to four species (Lophuromys
      sikapusi, Mus musculoides, Mastomys erythroleucus, and Crocidura olivieri) were
      recorded in the rehabilitated areas. Our data suggested negative effects of
      mining on small mammal diversity and the restoration of species diversity and
      important ecological processes after rehabilitation of altered habitats. We
      strongly encourage deliberate conservation efforts, particularly the development
      of management plans that require the restoration of degraded land resulting from
      mining activities.

PMID- 28451960
TI  - Non-point source contribution and dynamics of soluble and particulate phosphorus
      from main tributaries of the Zarivar Lake watershed, Iran.
AB  - The temporal variability of phosphorus (P) transport and the relationships
      between discharge, suspended sediment concentration and particulate (PP), and
      soluble (SP) phosphorus were examined. The study was conducted at the event scale
      in seven tributaries of the Zarivar Lake watershed in Kurdistan Province (Iran)
      from March 2011 to April 2012. Based on eight runoff events, 82% of the total P
      was the PP carried out by suspended sediment. Results showed a high variability
      of P transport during different runoff events. It was found that soil erosion was
      the source of the high P load. For all tributaries, PP was linearly related to
      both discharge and suspended sediment concentration. However, the relationships
      of SP and PP with discharge and suspended sediment concentration showed different
      hysteresis patterns. The relationship between PP and discharge was generally
      characterized by a clockwise pattern (i.e., lower part contribution of the sub
      watersheds) but the patterns between SP and discharge were mainly anticlockwise
      (i.e., upper part contribution of the sub-watersheds or perhaps due to a
      subsurface flow contribution).

PMID- 28451961
TI  - Environmental audits and process flow mapping to assess management of solid waste
      and wastewater from a healthcare facility: an Italian case study.
AB  - In Europe, there are an increasing number of policy and legislative drivers for a
      more sustainable approach to the management of natural resources as well as for
      the mitigation of environmental health risks. However, despite significant
      progress in recent years, there is still some way to go to achieve circularity of
      process, as well as risk mitigation within organisations. Using a case study of
      the Gardone Val Trompia hospital in northern Italy, this manuscript offers a
      novel holistic examination of strategies to enhance resource efficiency and
      environmental health within a key sector, i.e. the healthcare sector. Through the
      use of environmental audits and process flow mapping, trends in waste and
      wastewater arisings and the associated financial and environmental costs and
      risks were identified. Recommendations for developing more resource efficient
      approaches as well as mitigating the environmental and public health risks are
      suggested. These include strategies for improved resource efficiency (including
      reduction in the hazardous waste) and reduced environmental impacts during the
      containment, transport and treatment of the waste.

PMID- 28451962
TI  - Estimation of green house gas emissions from Koteshwar hydropower reservoir,
      India.
AB  - The emissions of greenhouse gas (GHG) from soils are of significant importance
      for global warming. The biological and physico-chemical characteristics of soil
      affect the GHG emissions from soils of different land use types. Methane (CH4),
      nitrous oxide (N2O), and carbon dioxide (CO2) production rates from six forest
      and agricultural soil types in the Koteshwar hydropower reservoir catchments
      located in the Uttarakhand, India, were estimated and their relations with
      physico-chemical characteristics of soils were examined. The samples of different
      land use types were flooded and incubated under anaerobic condition at 30 
      degrees C for 60 days. The cumulative GHG production rates in reservoir catchment
      are found as 1.52 +/- 0.26, 0.13 +/- 0.02, and 0.0004 +/- 0.0001 MUg g soil-1 day
      1 for CO2, CH4, and N2O, respectively, which is lower than global reservoirs
      located in the same eco-region. The significant positive correlation between CO2
      productions and labile organic carbon (LOC), CH4 and C/N ratio, while N2O and N/P
      ratio, while pH of soils is negatively correlated, conforms their key role in GHG
      emissions. Carbon available as LOC in the reservoir catchment is found as 3-14%
      of the total "C" available in soils and 0-23% is retained in the soil after the
      completion of incubation. The key objective of this study to signify the C, N,
      and P ratios, LOC, and pH with GHG production rate by creating an incubation
      experiment (as in the case of benthic soil/sediment) in the lab for 60 days. In
      summary, the results suggest that carbon, as LOC were more sensitive indicators
      for CO2 emissions and significant C, N, and P ratios, affects the GHG emissions.
      This study is useful for the hydropower industry to know the GHG production rates
      after the construction of reservoir so that its effect could be minimized by
      taking care of catchment area treatment plan.

PMID- 28451963
TI  - Erratum to: Adherence and Persistence Across Antidepressant Therapeutic Classes:
      A Retrospective Claims Analysis Among Insured US Patients with Major Depressive
      Disorder (MDD).

PMID- 28451964
TI  - Prospective assessment of patient-reported outcomes and estradiol and drug
      concentrations in patients experiencing toxicity from adjuvant aromatase
      inhibitors.
AB  - PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol
      concentrations in post-menopausal women, are associated with toxicities that
      limit adherence. Approximately one-third of patients will tolerate a different AI
      after not tolerating the first. We report the effect of crossover from exemestane
      to letrozole or vice versa on patient-reported outcomes (PROs) and whether the
      success of crossover is due to lack of estrogen suppression. METHODS: Post
      menopausal women enrolled on a prospective trial initiating AI therapy for early
      stage breast cancer were randomized to exemestane or letrozole. Those that
      discontinued for intolerance were offered protocol-directed crossover to the
      other AI after a washout period. Changes in PROs, including pain [Visual Analog
      Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were
      compared after 3 months on the first versus the second AI. Estradiol and drug
      concentrations were measured. RESULTS: Eighty-three patients participated in the
      crossover protocol, of whom 91.3% reported improvement in symptoms prior to
      starting the second AI. Functional status worsened less after 3 months with the
      second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: -0.05 [SD 0.36]; p =
      0.001); change in pain scores was similar between the first and second AI (VAS
      mean change AI #1: 0.8 [SD 2.7] vs. AI #2: -0.2 [SD 2.8]; p = 0.19). No
      statistical differences in estradiol or drug concentrations were found between
      those that continued or discontinued AI after crossover. CONCLUSIONS: Although
      all AIs act via the same mechanism, a subset of patients intolerant to one AI
      report improved PROs with a different one. The mechanism of this tolerance
      remains unknown, but does not appear to be due to non-adherence to, or
      insufficient estrogen suppression by, the second AI.

PMID- 28451965
TI  - A breast cancer gene signature for indolent disease.
AB  - PURPOSE: Early-stage hormone-receptor positive breast cancer is treated with
      endocrine therapy and the recommended duration of these treatments has increased
      over time. While endocrine therapy is considered less of a burden to patients
      compared to chemotherapy, long-term adherence may be low due to potential adverse
      side effects as well as compliance fatigue. It is of high clinical utility to
      identify subgroups of breast cancer patients who may have excellent long-term
      survival without or with limited duration of endocrine therapy to aid in
      personalizing endocrine treatment. METHODS: We describe a new ultralow risk
      threshold for the 70-gene signature (MammaPrint) that identifies a group of
      breast cancer patients with excellent 20 year, long-term survival prognosis.
      Tumors of these patients are referred to as "indolent breast cancer." We used
      patient series on which we previously established and assessed the 70-gene
      signature high-low risk threshold. RESULTS: In an independent validation cohort,
      we show that patients with indolent breast cancer had 100% breast cancer-specific
      survival at 15 years of follow-up. CONCLUSIONS: Our data indicate that patients
      with indolent disease may be candidates for limited treatment with adjuvant
      endocrine therapy based on their very low risk of distant recurrences or death of
      breast cancer.

PMID- 28451966
TI  - Phenotypic characterisation of breast cancer: the role of CDC42.
AB  - PURPOSE: The molecular landscape of breast cancer (BC), especially of the Luminal
      A subtype, remains to be fully delineated. Transcriptomic data show that Luminal
      A tumours are enriched for aberrant expression of genes in the cell division
      control 42 homolog (CDC42) pathway. This study aims to investigate the protein
      expression of CDC42 in BC and assess its clinicopathological significance.
      METHODS: Expression of CDC42 protein was examined by immunohistochemistry on
      tissue microarrays in a well-characterised cohort of 895 early-stage (I-IIIa)
      primary invasive BCs. RESULTS: CDC42 expression was observed in both the
      cytoplasm and the nucleus of BC cells. High nuclear CDC42 expression demonstrated
      a significant correlation with ER-positive, low-grade tumours and was more common
      in the lobular histological subtype (all p < 0.001). In contrast, cytoplasmic
      CDC42 showed increased expression in the ductal subtype (p < 0.001) and
      correlated with negative prognostic features such as larger size, higher grade (p
      < 0.05) and higher Ki67 labelling index (p = 0.001). Nuclear CDC42 expression was
      associated with a longer BC-specific survival in all cases (p = 0.025) and in
      luminal ER-positive tumours (p = 0.011). In multivariate analyses including size,
      grade, lymph node stage and intrinsic subtype, CDC42 was an independent
      prognostic factor (p = 0.032). CONCLUSION: The results indicate that CDC42 is an
      important molecule in luminal BC, with prognostic significance.

PMID- 28451967
TI  - Using PFP and ESG Protein Function Prediction Web Servers.
AB  - Elucidating biological function of proteins is a fundamental problem in molecular
      biology and bioinformatics. Conventionally, protein function is annotated based
      on homology using sequence similarity search tools such as BLAST and FASTA. These
      methods perform well when obvious homologs exist for a query sequence; however,
      they will not provide any functional information otherwise. As a result, the
      functions of many genes in newly sequenced genomes are left unknown, which await
      functional interpretation. Here, we introduce two webservers for function
      prediction methods, which effectively use distantly related sequences to improve
      function annotation coverage and accuracy: Protein Function Prediction (PFP) and
      Extended Similarity Group (ESG). These two methods have been tested extensively
      in various benchmark studies and ranked among the top in community-based
      assessments for computational function annotation, including Critical Assessment
      of Function Annotation (CAFA) in 2010-2011 (CAFA1) and 2013-2014 (CAFA2). Both
      servers are equipped with user-friendly visualizations of predicted GO terms,
      which provide intuitive illustrations of relationships of predicted GO terms. In
      addition to PFP and ESG, we also introduce NaviGO, a server for the interactive
      analysis of GO annotations of proteins. All the servers are available at
      http://kiharalab.org/software.php .

PMID- 28451968
TI  - GHOSTX: A Fast Sequence Homology Search Tool for Functional Annotation of
      Metagenomic Data.
AB  - Metagenomic analysis based on whole genome shotgun sequencing data requires fast
      protein sequence homology searches for predicting the function of proteins coded
      on metagenome short reads. However, huge amounts of sequence data cause even
      general homology search analyses using BLASTX to become difficult in terms of
      computational cost. GHOSTX is a sequence homology search tool specifically
      developed for functional annotation of metagenome sequences. The tool is more
      than 160 times faster than BLASTX and has sufficient search sensitivity for
      metagenomic analysis. Using this tool, user can perform functional annotation of
      metagenomic data within a short time and infer metabolic pathways within an
      environment.

PMID- 28451969
TI  - From Gene Annotation to Function Prediction for Metagenomics.
AB  - Microbes play important roles in almost every aspect of life, including human
      health and diseases. Facilitated by the rapid development of sequencing
      technologies, metagenomics research has accelerated the accumulation of genomic
      sequences of microbial species that had been inaccessible before. Analysis of the
      metagenomic sequencing data can reveal not only the species but also the
      functional composition of microbial communities. Here, we report a pipeline for
      functional annotation of metagenomic datasets. The pipeline is built from several
      programs that we have developed for metagenomic sequence analysis including a
      protein-coding gene predictor for short reads (or contigs) and a fast similarity
      search tool. Given a metagenomic dataset, the pipeline reports putative protein
      coding genes (or gene fragments) and functional annotations of the genes in Gene
      Ontology (GO) terms and Enzyme Commission (EC) numbers, and potential metabolic
      pathways that are likely encoded by the metagenome. Fun4Me is available for
      download at https://sourceforge.net/projects/fun4me .

PMID- 28451970
TI  - An Agile Functional Analysis of Metagenomic Data Using SUPER-FOCUS.
AB  - One of the main goals in metagenomics is to identify the functional profile of a
      microbial community from unannotated shotgun sequencing reads. Functional
      annotation is important in biological research because it enables researchers to
      identify the abundance of functional genes of the organisms present in the
      sample, answering the question, "What can the organisms in the sample do?" Most
      currently available approaches do not scale with increasing data volumes, which
      is important because both the number and lengths of the reads provided by
      sequencing platforms keep increasing. Here, we present SUPER-FOCUS, SUbsystems
      Profile by databasE Reduction using FOCUS, an agile homology-based approach using
      a reduced reference database to report the subsystems present in metagenomic
      datasets and profile their abundances. SUPER-FOCUS was tested with real
      metagenomes, and the results show that it accurately predicts the subsystems
      present in the profiled microbial communities, is computationally efficient, and
      up to 1000 times faster than other tools. SUPER-FOCUS is freely available at
      http://edwards.sdsu.edu/SUPERFOCUS .

PMID- 28451971
TI  - MPFit: Computational Tool for Predicting Moonlighting Proteins.
AB  - An increasing number of proteins have been found which are capable of performing
      two or more distinct functions. These proteins, known as moonlighting proteins,
      have drawn much attention recently as they may play critical roles in disease
      pathways and development. However, because moonlighting proteins are often found
      serendipitously, our understanding of moonlighting proteins is still quite
      limited. In order to lay the foundation for systematic moonlighting proteins
      studies, we developed MPFit, a software package for predicting moonlighting
      proteins from their omics features including protein-protein and gene interaction
      networks. Here, we describe and demonstrate the algorithm of MPFit, the idea
      behind it, and provide instruction for using the software.

PMID- 28451972
TI  - Predicting Secretory Proteins with SignalP.
AB  - SignalP is the currently most widely used program for prediction of signal
      peptides from amino acid sequences. Proteins with signal peptides are targeted to
      the secretory pathway, but are not necessarily secreted. After a brief
      introduction to the biology of signal peptides and the history of signal peptide
      prediction, this chapter will describe all the options of the current version of
      SignalP and the details of the output from the program. The chapter includes a
      case study where the scores of SignalP were used in a novel way to predict the
      functional effects of amino acid substitutions in signal peptides.

PMID- 28451973
TI  - The ProFunc Function Prediction Server.
AB  - The ProFunc web server is a tool for helping identify the function of a given
      protein whose 3D coordinates have been experimentally determined or homology
      modeled. It uses a cocktail of both sequence- and structure-based methods to
      identify matches to other proteins that may, in turn, suggest the query protein's
      most likely function. The server was originally developed to aid the worldwide
      structural genomics effort at the start of the millennium. It accepts a file
      containing the protein's 3D coordinates in PDB format, and, when processing is
      complete, sends an email containing a link to the password-protected result
      pages. The results include an at-a-glance summary, as well as separate pages
      containing more detailed analyses. The server can be found at:
      http://www.ebi.ac.uk/thornton-srv/databases/profunc .

PMID- 28451974
TI  - G-LoSA for Prediction of Protein-Ligand Binding Sites and Structures.
AB  - Recent advances in high-throughput structure determination and computational
      protein structure prediction have significantly enriched the universe of protein
      structure. However, there is still a large gap between the number of available
      protein structures and that of proteins with annotated function in high accuracy.
      Computational structure-based protein function prediction has emerged to reduce
      this knowledge gap. The identification of a ligand binding site and its structure
      is critical to the determination of a protein's molecular function. We present a
      computational methodology for predicting small molecule ligand binding site and
      ligand structure using G-LoSA, our protein local structure alignment and
      similarity measurement tool. All the computational procedures described here can
      be easily implemented using G-LoSA Toolkit, a package of standalone software
      programs and preprocessed PDB structure libraries. G-LoSA and G-LoSA Toolkit are
      freely available to academic users at http://compbio.lehigh.edu/GLoSA . We also
      illustrate a case study to show the potential of our template-based approach
      harnessing G-LoSA for protein function prediction.

PMID- 28451975
TI  - Local Alignment of Ligand Binding Sites in Proteins for Polypharmacology and Drug
      Repositioning.
AB  - The administration of drugs is a key strategy in pharmacotherapy to treat
      diseases. Drugs are typically developed to modulate the function of specific
      proteins, which are directly associated with particular disease states.
      Nonetheless, recent studies suggest that protein-drug interactions are rather
      promiscuous and the majority of pharmaceuticals exhibit activity against
      multiple, often unrelated proteins. Certainly, the lack of selectivity often
      leads to drug side effects; on the other hand, these polypharmacological
      attributes can be used to develop drugs acting on multiple targets within a
      unique disease pathway, as well as to identify new targets for existing drugs,
      which is known as drug repositioning. To support drug development and
      repurposing, we developed eMatchSite, a new approach to detect those binding
      sites having the capability to bind similar compounds. eMatchSite is available as
      a standalone software and a webserver at http://www.brylinski.org/ematchsite .

PMID- 28451976
TI  - WATsite2.0 with PyMOL Plugin: Hydration Site Prediction and Visualization.
AB  - Water molecules in the binding site of a protein significantly influence protein
      structure and function, for example, by mediating protein-ligand interactions or
      due to water displacement as driving force for ligand binding. The knowledge
      about location and thermodynamic contributions of binding site water molecules is
      crucial for understanding protein function. WATsite is a hydration site analysis
      program that was developed together with an easy-to-use graphical user interface
      (GUI) based on PyMOL. WATsite identifies hydration sites from a molecular
      dynamics (MD) simulation trajectory with four different types of explicit water
      molecules. Hydration sites can be identified with or without the presence of a
      bound ligand dependent on the scientific problem. The protein desolvation free
      energy can be estimated for any ligand by summation of the hydration site free
      energies of the displaced hydration sites. The location and thermodynamic profile
      of hydration sites mediating the protein-ligand interactions is important for
      understanding protein-ligand binding. The WATsite program and GUI are available
      free of charge from
      http://people.pharmacy.purdue.edu/~mlill/software/watsite/version2.shtml .

PMID- 28451977
TI  - Enzyme Annotation and Metabolic Reconstruction Using KEGG.
AB  - KEGG is an integrated database resource for linking sequences to biological
      functions from molecular to higher levels. Knowledge on molecular functions is
      stored in the KO (KEGG Orthology) database, while cellular- and organism-level
      functions are represented in the PATHWAY and MODULE databases. Genes in the
      complete genomes, which are stored in the GENES database, are given KO
      identifiers by the internal annotation procedure, enabling reconstruction of KEGG
      pathways and modules for interpretation of higher-level functions. This is
      possible because all the KEGG pathways and modules are represented as networks of
      KO nodes. Here we present knowledge-based prediction methods for functional
      characterization of amino acid sequences using the KEGG resource. Specifically we
      show how the tools available at the KEGG website including BlastKOALA and KEGG
      Mapper can be utilized for enzyme annotation and metabolic reconstruction.

PMID- 28451978
TI  - Ortholog Identification and Comparative Analysis of Microbial Genomes Using MBGD
      and RECOG.
AB  - Comparative genomics is becoming an essential approach for identification of
      genes associated with a specific function or phenotype. Here, we introduce the
      microbial genome database for comparative analysis (MBGD), which is a
      comprehensive ortholog database among the microbial genomes available so far.
      MBGD contains several precomputed ortholog tables including the standard ortholog
      table covering the entire taxonomic range and taxon-specific ortholog tables for
      various major taxa. In addition, MBGD allows the users to create an ortholog
      table within any specified set of genomes through dynamic calculations. In
      particular, MBGD has a "My MBGD" mode where users can upload their original
      genome sequences and incorporate them into orthology analysis. The created
      ortholog table can serve as the basis for various comparative analyses. Here, we
      describe the use of MBGD and briefly explain how to utilize the orthology
      information during comparative genome analysis in combination with the stand
      alone comparative genomics software RECOG, focusing on the application to
      comparison of closely related microbial genomes.

PMID- 28451979
TI  - Exploring Protein Function Using the Saccharomyces Genome Database.
AB  - Elucidating the function of individual proteins will help to create a
      comprehensive picture of cell biology, as well as shed light on human disease
      mechanisms, possible treatments, and cures. Due to its compact genome, and
      extensive history of experimentation and annotation, the budding yeast
      Saccharomyces cerevisiae is an ideal model organism in which to determine protein
      function. This information can then be leveraged to infer functions of human
      homologs. Despite the large amount of research and biological data about S.
      cerevisiae, many proteins' functions remain unknown. Here, we explore ways to use
      the Saccharomyces Genome Database (SGD; http://www.yeastgenome.org ) to predict
      the function of proteins and gain insight into their roles in various cellular
      processes.

PMID- 28451980
TI  - Network-Based Gene Function Prediction in Mouse and Other Model Vertebrates Using
      MouseNet Server.
AB  - The mouse, Mus musculus, is a popular model organism for the study of human genes
      involved in development, immunology, and disease phenotypes. Despite recent
      revolutions in gene-knockout technologies in mouse, identification of candidate
      genes for functions of interest can further accelerate the discovery of novel
      gene functions. The collaborative nature of genetic functions allows for the
      inference of gene functions based on the principle of guilt-by-association.
      Genome-scale co-functional networks could therefore provide functional
      predictions for genes via network analysis. We recently constructed such a
      network for mouse (MouseNet), which interconnects over 88% of protein-coding
      genes with 788,080 functional relationships. The companion web server (
      www.inetbio.org/mousenet ) enables researchers with no bioinformatics expertise
      to generate predictions that facilitate discovery of novel gene functions. In
      this chapter, we present the theoretical framework for MouseNet, as well as step
      by-step instructions and technical tips for functional prediction of genes and
      pathways in mouse and other model vertebrates.

PMID- 28451981
TI  - The FANTOM5 Computation Ecosystem: Genomic Information Hub for Promoters and
      Active Enhancers.
AB  - The Functional Annotation of the Mammalian Genome 5 (FANTOM5) project conducted
      transcriptome analysis of various mammalian cell types and provided a
      comprehensive resource to understand transcriptome and transcriptional regulation
      in individual cellular states encoded in the genome.FANTOM5 used cap analysis of
      gene expression (CAGE) with single-molecule sequencing to map transcription start
      sites (TSS) and measured their expression in a diverse range of samples. The main
      results from FANTOM5 were published as a promoter-level mammalian expression
      atlas and an atlas of active enhancers across human cell types. The FANTOM5
      dataset is composed of raw experimental data and the results of bioinformatics
      analyses. In this chapter, we give a detailed description of the content of the
      FANTOM5 dataset and elaborate on different computing applications developed to
      publish the data and enable reproducibility and discovery of new findings. We
      present use cases in which the FANTOM5 dataset has been reused, leading to new
      findings.

PMID- 28451982
TI  - Multi-Algorithm Particle Simulations with Spatiocyte.
AB  - As quantitative biologists get more measurements of spatially regulated systems
      such as cell division and polarization, simulation of reaction and diffusion of
      proteins using the data is becoming increasingly relevant to uncover the
      mechanisms underlying the systems. Spatiocyte is a lattice-based stochastic
      particle simulator for biochemical reaction and diffusion processes. Simulations
      can be performed at single molecule and compartment spatial scales
      simultaneously. Molecules can diffuse and react in 1D (filament), 2D (membrane),
      and 3D (cytosol) compartments. The implications of crowded regions in the cell
      can be investigated because each diffusing molecule has spatial dimensions.
      Spatiocyte adopts multi-algorithm and multi-timescale frameworks to simulate
      models that simultaneously employ deterministic, stochastic, and particle
      reaction-diffusion algorithms. Comparison of light microscopy images to
      simulation snapshots is supported by Spatiocyte microscopy visualization and
      molecule tagging features. Spatiocyte is open-source software and is freely
      available at http://spatiocyte.org .

PMID- 28451983
TI  - Therapeutic Targeting of PDEs and PI3K in Heart Failure with Preserved Ejection
      Fraction (HFpEF).
AB  - PURPOSE OF REVIEW: Heart Failure with preserved Ejection Fraction (HFpEF) is a
      prevalent disease with considerable individual and societal burden. HFpEF
      patients often suffer from multiple pathological conditions thatcomplicate
      management and adversely affect outcome, including pulmonary hypertension and
      chronic obstructive pulmonary disease (COPD). To date, no treatment proved to be
      fully effective in reducing morbidity and mortality in HFpEF, possibly due to an
      incomplete understanding of the underlying molecular mechanisms. RECENT FINDINGS:
      The emerging view proposes chronic systemic inflammation, leading to endothelial
      dysfunction and interstitial fibrosis, as a prominent cause of HFpEF, rather than
      a mere co-existent disease. In the last decade, efforts from pharmaceutical
      companies attempted to target pharmacologically enzymes which play key roles in
      systemic and lung inflammation, such as the cyclic nucleotide-degrading enzymes
      phosphodiesterases (PDEs) and phosphoinositide-3 phosphate kinases (PI3Ks),
      especially to limit COPD. In this review, we will summarize major successes and
      drawbacks of hitting these enzymes to tackle inflammation in HFpEF-associated co
      morbidities, with a major focus on the results of completed and ongoing clinical
      trials. Finally, we will discuss the potential of repurposing and/or developing
      new PDE and PI3K inhibitors for HFpEF therapy.

PMID- 28451984
TI  - From Medical to Recreational Marijuana Sales: Marijuana Outlets and Crime in an
      Era of Changing Marijuana Legislation.
AB  - A movement from medical to recreational marijuana use allows for a larger base of
      potential users who have easier access to marijuana, because they do not have to
      visit a physician before using marijuana. This study examines whether changes in
      the density of marijuana outlets were related to violent, property, and marijuana
      specific crimes in Denver, CO during a time in which marijuana outlets began
      selling marijuana for recreational, and not just medical, use. We collected data
      on locations of crimes, marijuana outlets and covariates for 481 Census block
      groups over 34 months (N = 16,354 space-time units). A Bayesian Poisson space
      time model assessed statistical relationships between independent measures and
      crime counts within "local" Census block groups. We examined spatial "lag"
      effects to assess whether crimes in Census block groups adjacent to locations of
      outlets were also affected. Independent of the effects of covariates, densities
      of marijuana outlets were unrelated to property and violent crimes in local
      areas. However, the density of marijuana outlets in spatially adjacent areas was
      positively related to property crime in spatially adjacent areas over time.
      Further, the density of marijuana outlets in local and spatially adjacent blocks
      groups was related to higher rates of marijuana-specific crime. This study
      suggests that the effects of the availability of marijuana outlets on crime do
      not necessarily occur within the specific areas within which these outlets are
      located, but may occur in adjacent areas. Thus studies assessing the effects of
      these outlets in local areas alone may risk underestimating their true effects.

PMID- 28451985
TI  - Prophylactic accessory renal artery coil embolization for prevention of type II
      endoleak following endovascular aneurysm repair: a case report.
AB  - BACKGROUND: Prior reports indicate that intentional coverage of the accessory
      renal arteries (ARAs) with a diameter larger than 3 mm during endovascular
      aneurysm repair (EVAR) increases risk of additional treatment for type II
      endoleak. Here, we report a case of prophylactic coil embolization for a 4 mm ARA
      originating from an abdominal aortic aneurysm. CASE PRESENTATION: A 76-year-old
      woman was admitted to our hospital after noticing an abdominal pulsatile mass.
      Computed tomography (CT) imaging revealed an abdominal aortic aneurysm (AAA) with
      a maximum diameter of 53 mm. Preoperative CT scan showed a right ARA, 4 mm in
      diameter, which was considered likely to lead to type II endoleak following EVAR.
      ARA coil embolization was performed at the time of EVAR. We observed no endoleaks
      and no infarct of the inferior pole of the right kidney on completion
      angiography. The postoperative course was uneventful, and the patient was
      discharged 7 days later. Postoperative eGFR (58.4 ml/min) was not significantly
      different from preoperative level (56.7 ml/min). After EVAR, blood pressure was
      under control, and no additional anti-hypertensive medicines were required.
      Postoperative enhanced CT image showed that the distal portion of the ARA was
      well perfused without type II endoleak from ARA. CONCLUSIONS: Prophylactic coil
      embolization for a large ARA originating from an abdominal aortic aneurysm
      appears to be safe and effective in preventing type II endoleak following EVAR.

PMID- 28451986
TI  - Bt Proteins Have No Detrimental Effects on Larvae of the Green Lacewing, Chrysopa
      pallens (Rambur) (Neuroptera: Chrysopidae).
AB  - Biosafety of a genetically modified crop is required to be assessed prior to its
      commercialization. For this, a suitable artificial diet was developed and used to
      establish a dietary exposure test for assessing the toxicity of midgut-active Bt
      insecticidal proteins on Chrysopa pallens (Rambur). Subsequently, this dietary
      exposure test was used to evaluate the toxicity of the proteins Cry1Ab, Cry1Ac,
      Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, and Vip3Aa on C. pallens larvae. Temporal
      stability, bioactivity, and the intake of the insecticidal proteins were
      confirmed by enzyme-linked immunosorbent assay and a sensitive-insect bioassay.
      The life history characteristics, such as survival, pupation, adult emergence, 7
      day larval weight, larval developmental time, and emerged male and female fresh
      weights remained unaffected, when C. pallens were fed the pure artificial diet
      (negative control) and the artificial diets containing 200 MUg/g of each purified
      protein: Cry1Ab, Cry1Ac, Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, or Vip3Aa. On the
      contrary, all of the life history characteristics of C. pallens larvae were
      adversely affected when fed artificial diet containing boric acid (positive
      control). The results demonstrate that diets containing the tested concentrations
      of Cry1Ab, Cry1Ac, Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, and Vip3Aa have null
      effects on C. pallens larvae. The outcome indicates that genetically modified
      crops expressing the tested Bt proteins are safe for the lacewing, C. pallens.

PMID- 28451987
TI  - ERG and other discriminators between advanced hydroxychloroquine retinopathy and
      retinitis pigmentosa.
AB  - PURPOSE: To study whether the ERG and other clinical findings help to distinguish
      between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse
      retinitis pigmentosa (RP) with similar fundus appearance. METHODS: We conducted a
      retrospective analysis of patients with advanced HCQ retinopathy (n = 11),
      pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as
      having limited fundus damage and relatively normal flicker ERG time-to-peak.
      Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients
      showed reduced amplitude of the ISCEV responses in the full-field
      electroretinogram (ERG). Aspects of history, visual field results, fundus
      appearance, fundus autofluorescence and ocular coherence tomography were also
      compared. RESULTS: Relative to pericentral RP, patients with HCQ toxicity showed
      delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined
      rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some
      preserved rod ERG response, and there was no obvious predilection for rod over
      cone damage. In addition, patients with HCQ toxicity usually lacked markers of
      long-standing degeneration such as bone spicule figures or severe loss of
      peripheral field. History of familial disease and long-standing night blindness
      were specific to RP. CONCLUSIONS: While the early signs of HCQ damage are
      typically regional in the posterior pole, advanced disease is characteristically
      diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is
      the finding that rods and cones were both affected in the ERG to a similar degree
      (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and
      some of our discriminatory findings, and no family history or prior night
      blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare
      disease (Occam's razor).

PMID- 28451988
TI  - Correlation of macular structure and function in a boy with primary foveomacular
      retinitis and sequence of changes over 5 years.
AB  - PURPOSE: To describe the clinical characteristics, macular structure and
      function, and to document sequential changes over 5 years in a 10-year-old boy
      with bilateral primary foveomacular retinitis. METHODS: A 10-year-old boy
      presented with sudden onset scotoma in both eyes, experienced after getting up
      from bed on a non-eclipse day. He persistently denied direct sun-gazing. He
      neither had any significant systemic illness, nor was using any medications. In
      addition to a detailed examination at presentation that included fundus
      fluorescein angiogram (FFA), electroretinogram (ERG), pattern ERG and
      electrooculogram (EOG), he was examined periodically for 5 years with Humphrey
      visual field (HVF), spectral domain optical coherence tomogram (SDOCT), Amsler
      grid charting and multifocal ERG. The macular structure and functions were
      analyzed over the years and correlated with the symptoms. RESULTS: All findings
      were bilaterally symmetrical at each visit. At presentation, his corrected visual
      acuity was 20/25 with subfoveal yellow dot similar to solar retinopathy, central
      scotoma with reduced foveal threshold in HVF 24-2, micropsia in Amsler grid,
      missing of two plates on Ishihara color vision chart, transfoveal full thickness
      hyper-reflective band on SD OCT, unremarkable FFA and normal foveal peak in
      mfERG. The flash ERG and EOG were unremarkable. A month later, his VA improved to
      20/20, he had relative scotoma in Amsler grid, no scotoma in HVF (10-2),
      restoration of the inner segment of the photoreceptors with sharp defect
      involving ellipsoid and photoreceptor interdigitation zone in SDOCT and blunting
      of foveal peaks in mfERG. Three months later, his corrected VA was 20/20 with
      relative scotoma in Amsler grid, normal color vision, no scotoma in HVF 10-2 and
      unchanged SDOCT findings. In subsequent examinations at 6, 9, 14, 29, 39 and 60
      months, he was symptomless with VA 20/20, unremarkable fundus, normal Amsler grid
      and HVF (normal foveal threshold), unchanged SDOCT findings and the reduced
      foveal peaks on mfERG in both eyes got normalized only at 60 months. CONCLUSION:
      Presented here is a case of bilaterally symmetrical idiopathic foveomacular
      retinitis that had a clinical appearance similar to solar retinopathy. The fundus
      changes persisted for 4 weeks, the symptoms and changes in Amsler grid lasted for
      3 months, and the foveal threshold in visual fields normalized within 3 months.
      Maximum change in the SDOCT defect occurred within a month, and the extrafoveal
      defect in the ellipsoid and photoreceptor interdigitation line persisted despite
      resolution of symptoms and resolution of the visual field defect and normal
      distance vision. Probably, the foveal lesion detected on SDOCT was too small to
      cause a reduction in the distance visual acuity or show up in the visual field
      and mfERG later.

PMID- 28451989
TI  - Tissue Engineered Human Amniotic Membrane Application in Mouse Ovarian Follicular
      Culture.
AB  - Since folliculogenesis requires a powerful cell-matrix interaction, natural
      scaffolds seem to be needed for follicular culture. Human amniotic membrane (HAM)
      offers promise as a support of in vitro ovarian follicular culture. HAM was
      decellularized with trypsin and EDTA. DNA and histology assays were performed to
      determine the elimination rate of genomic components. Cyto-biocompatibility of
      decellular AM (DAM) was verified by the cell viability (MTT) test. The small
      parts of intact amniotic membrane (IAM) and DAM were coated on the bottom of 96
      well and each well was filled with 150 uL of base medium. Mouse primary-secondary
      (PS) follicles were separated to three groups: 1-culture in base medium
      (Control), 2-culture on IAM and 3-culture on DAM. Follicular size, morphology,
      viability, estradiol production and genes expression were evaluated and IAM group
      showed better growth and development in follicle culture. The viability rate and
      estradiol production in both experimental groups were statistically higher than
      the Control. Gdf9, Bmp15 and Cx37 were found to have higher expression levels in
      IAM group. Also, maximum apoptotic and survival indexes were determined in
      Control and IAM groups, respectively. Finally, IAM provides a better protective
      environment for mouse PS follicular culture that can reduce apoptosis level.

PMID- 28451990
TI  - Chest Wall Kinematics Using Triangular Cosserat Point Elements in Healthy and
      Neuromuscular Subjects.
AB  - Optoelectronic plethysmography (OEP) is a noninvasive method for assessing lung
      volume variations and the contributions of different anatomical compartments of
      the chest wall (CW) through measurements of the motion of markers attached to the
      CW surface. The present study proposes a new method for analyzing the local CW
      kinematics from OEP measurements based on the kinematics of triangular Cosserat
      point elements (TCPEs). 52 reflective markers were placed on the anterior CW to
      create a mesh of 78 triangles according to an anatomical model. Each triangle was
      characterized by a TCPE and its kinematics was described using four time-variant
      scalar TCPE parameters. The total CW volume ([Formula: see text]) and the
      contributions of its six compartments were also estimated, using the same
      markers. The method was evaluated using measurements of ten healthy subjects,
      nine patients with Pompe disease, and ten patients with Duchenne muscular
      dystrophy (DMD), during spontaneous breathing (SB) and vital capacity maneuvers
      (VC) in the supine position. TCPE parameters and compartmental volumes were
      compared with [Formula: see text] by computing the phase angles [Formula: see
      text] (for SB) and the correlation r (for VC) between them. Analysis of [Formula:
      see text] and r of the outward translation parameter [Formula: see text] of each
      TCPE revealed that for healthy subjects it provided similar results to those
      obtained by compartmental volumes, whereas for the neuromuscular patients the
      TCPE method was capable of detecting local asynchronous and paradoxical movements
      also in cases where they were undistinguished by volumes. Therefore, the TCPE
      approach provides additional information to OEP that may enhance its clinical
      evaluation capabilities.

PMID- 28451991
TI  - [18F]FP-(+)-DTBZ PET study in a lactacystin-treated rat model of Parkinson
      disease.
AB  - OBJECTIVE: Lactacystin has been used to establish rodent models of Parkinson
      disease (PD), with cerebral alpha-synuclein inclusions. This study evaluated the
      uptake of [18F]9-fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ), a
      vesicular monoamine transporter type 2 (VMAT2)-targeting radiotracer, through
      positron emission tomography (PET) in lactacystin-treated rat brains. METHODS:
      Adult male Sprague-Dawley rats were randomly treated with a single intracranial
      dose of lactacystin (2 or 5 MUg) or saline (served as the sham control) into the
      left medial forebrain bundle. A 30-min static [18F]FP-(+)-DTBZ brain PET scan was
      performed following an intravenous [18F]FP-(+)-DTBZ dose (approximately 22 MBq)
      in each animal at 2 and 3 weeks after lactacystin treatment. Upon completing the
      last PET scans, the animals were killed, and their brains were dissected for ex
      vivo autoradiography (ARG) and immunohistochemical (IHC) staining of tyrosine
      hydroxylase (TH) as well as VMAT2. RESULTS: Both the 2- and 5-MUg lactacystin
      treated groups exhibited significantly decreased specific [18F]FP-(+)-DTBZ uptake
      in the ipsilateral striata (I-ST) at 2 weeks (1.51 and 1.16, respectively) and 3
      weeks (1.36 and 1.00, respectively) after lactacystin treatment, compared with
      the uptake in the corresponding contralateral striata (C-ST) (3.48 and 3.08 for
      the 2- and 5-MUg lactacystin-treated groups, respectively, at 2 weeks; 3.36 and
      3.11 for the 2- and 5-MUg lactacystin-treated groups, respectively, at 3 weeks)
      and the sham controls (3.34-3.53). Lactacystin-induced decline in I-ST [18F]FP
      (+)-DTBZ uptake was also demonstrated through ex vivo ARG, and the corresponding
      dopaminergic neuron damage was confirmed by the results of TH- and VMAT2-IHC
      studies. CONCLUSIONS: In this PD model, lactacystin-induced dopaminergic terminal
      damage in the ipsilateral striatum could be clearly visualized through in vivo
      [18F]FP-(+)-DTBZ PET imaging. This may serve as a useful approach for evaluating
      the effectiveness of new treatments for PD.

PMID- 28451992
TI  - Is there any role for thoracic ultrasound for interstitial lung disease
      underlying rheumatologic conditions? Reply.

PMID- 28451993
TI  - Key rates for the grades and transformation ability of glioma: model simulations
      and clinical cases.
AB  - Tumor progression to higher grade is a fundamental property of cancer. The
      malignant advancement of the pathological features may either develop during the
      later stages of cancer growth (natural evolution) or it may necessitate new
      mutations or molecular events that alter the rates of growth, dispersion, or
      neovascularization (transformation). Here, we model the pathological and
      radiological features of grades 2-4 gliomas at the times of diagnosis and death
      and study grade development and the progression to higher grades. We perform a
      retrospective review of clinical cases based on model predictions. Simulations
      uncover two unusual patterns of glioma progression, which are supported by
      clinical cases: (1) some grades 2 and 3 gliomas lack the ability of progression
      to higher grades, and (2) grade 3 glioma may evolve to GBM in a few weeks. All 13
      gliomas that recurred at the same grade carry either the IDH1-R132H or the ATRX
      mutation. All (five of five) grade 3 tumors are 1p/19q co-deleted, IDH1-R132H
      mutated and ATRX wt. Furthermore, three of seven grade 2 gliomas are both IDH1
      R132H mutated and ATRX mutated. Simulations replicate the good prognosis of
      secondary GBM. The results support the hypothesis that constant rates of
      dispersion, proliferation, and angiogenesis prescribe either a natural evolution
      or the inability to progress to higher grades. Furthermore, the accrual of
      molecular events that change a tumor's ability to infiltrate, proliferate or
      neovascularize may transform the glioma either into a more aggressive tumor at
      the same grade or elevate its grade.

PMID- 28451995
TI  - A Protocol to Prepare Decellularized Stem Cell Matrix for Rejuvenation of Cell
      Expansion and Cartilage Regeneration.
AB  - Traditional ex vivo expansion of adult stem cells yields an insufficient quantity
      of less potent cells. Here we describe the fabrication of decellularized matrix
      deposited by synovium-derived stem cells (SDSCs). This matrix could serve as a
      three-dimensional expansion system to rejuvenate cells for proliferation and
      tissue-specific differentiation potential, which could benefit cartilage
      regeneration. The decellularized stem cell matrix (DSCM) might be a powerful
      system for tissue engineering and regeneration.

PMID- 28451994
TI  - 3D Stacked Construct: A Novel Substitute for Corneal Tissue Engineering.
AB  - Corneal trauma/injury often results in serious complications including permanent
      vision loss or loss of visual acuity which demands corneal transplantations or
      treatment with allogenic graft tissues. There is currently a huge shortage of
      donor tissue worldwide and the need for human corneal equivalents increases
      annually. In order to meet such demand the current clinical approach of treating
      corneal injuries is limited and involves synthetic and allogenic materials which
      have various shortcomings when it comes to actual transplantations. In this study
      we introduce the newly developed, next generation of our previously established
      3D self-assembled constructs, where multiple constructs are grown and stacked on
      top of each other without any other artificial product. This new technology
      brings our 3D in vitro model closer to what is seen in vivo and provides a solid
      foundation for future studies on corneal biology.Lipids are known for playing a
      vital role during metabolism and diseased state of various tissues and
      Sphingolipids are one such class of lipids which are involved in various cellular
      mechanisms and signaling processes. The impacts of Sphingolipids that have been
      documented in several human diseases often involve inflammation,
      neovascularization, tumorigenesis, and diabetes, but these conditions are not yet
      thoroughly studied. There is very little information about the exact role of
      Sphingolipids in the human cornea and future studies aiming at dissecting the
      mechanisms and pathways involved in order to develop novel therapies. We believe
      that our novel 3D stacked model can be used to delineate the role of
      Sphingolipids in the human cornea and provide new insights for understanding and
      treating various human corneal diseases.

PMID- 28451996
TI  - Mouse Skeletal Muscle Decellularization.
AB  - Natural acellular matrices obtained from decellularization procedures are
      biocompatible and non-immunogenic materials considered promising tools for
      regenerative medicine purposes. Before in vivo implantation, these matrices must
      be efficiently decellularized, removing all the cellular components to avoid any
      immunogenic reaction. At the same time, it is important to maintain the original
      three-dimensional structure of the specific tissue. Here we describe a method:
      (1) to decellularize mouse quadriceps using a detergent-enzymatic treatment (DET)
      and (2) to assess decellularization efficiency and scaffold properties.

PMID- 28451997
TI  - Decellularization of Bovine Small Intestinal Submucosa.
AB  - Decellularization technology promises to overcome some of the significant
      limitations in the regenerative medicine field by providing functional
      biocompatible grafts. The technique involves removal of the cells from the
      biological tissues or organs for further use in tissue engineering and clinical
      interventions. There are significant differences between decellularization
      protocols due to the intrinsic properties of different tissue types and purpose
      of use. This multistep, chemical-solution-based protocol is optimized for the
      preparation of decellularized bovine small intestinal submucosa (SIS).

PMID- 28451998
TI  - Voluntary action alters the perception of visual illusions.
AB  - "Intentional binding" refers to the finding that people judge voluntary actions
      and their effects as having occurred closer together in time than two passively
      observed events. If this effect reflects subjectively compressed time, then time
      dependent visual illusions should be altered by voluntary initiation. To test
      this hypothesis, we showed participants displays that result in particular motion
      illusions when presented at short interstimulus intervals (ISIs). In Experiment 1
      we used apparent motion, which is perceived only at very short ISIs; Experiments
      2a and 2b used the Ternus display, which results in different motion illusions
      depending on the ISI. In support of the time compression hypothesis, when they
      voluntarily initiated the displays, people persisted in seeing the motion
      illusions associated with short ISIs at longer ISIs than had been the case during
      passive viewing. A control experiment indicated that this effect was not due to
      predictability or increased attention. Instead, voluntary action altered motion
      illusions, despite their purported cognitive impenetrability.

PMID- 28451999
TI  - Faces are special, but facial expressions aren't: Insights from an oculomotor
      capture paradigm.
AB  - We compared the ability of angry and neutral faces to drive oculomotor behaviour
      as a test of the widespread claim that emotional information is automatically
      prioritized when competing for attention. Participants were required to make a
      saccade to a colour singleton; photos of angry or neutral faces appeared amongst
      other objects within the array, and were completely irrelevant for the task. Eye
      tracking measures indicate that faces drive oculomotor behaviour in a bottom-up
      fashion; however, angry faces are no more likely to capture the eyes than neutral
      faces are. Saccade latencies suggest that capture occurrs via reflexive saccades
      and that the outcome of competition between salient items (colour singletons and
      faces) may be subject to fluctuations in attentional control. Indeed, although
      angry and neutral faces captured the eyes reflexively on a portion of trials,
      participants successfully maintained goal-relevant oculomotor behaviour on a
      majority of trials. We outline potential cognitive and brain mechanisms
      underlying oculomotor capture by faces.

PMID- 28452000
TI  - Ultrasound characterization of insulin induced lipohypertrophy in type 1 diabetes
      mellitus.
AB  - OBJECTIVE: Subcutaneous insulin absorption is one of the key factors affecting
      glycemic control in patients with diabetes mellitus under insulin therapy.
      Insulin-induced subcutaneous lipohypertrophy has been reported to impair insulin
      regular absorption and hence glycemic control. So far, lipohypertrophy diagnosis
      has only been clinical. This study aims at evaluating the possible role of
      ultrasound scan in the assessment of subcutaneous lipohypertrophy in patients
      affected by type 1 diabetes mellitus. METHODS: A pilot observational
      retrospective study was performed in 20 patients affected by type 1 diabetes
      mellitus. In these patients the areas with clinical evidence of lipohypertrophy
      dependent on the insulin injections were characterized by the presence of tissues
      that at the ultrasound scan resulted similar to fibrotic tissues (hyperechogenic)
      or to an interstitial edema or to fat tissues (hypoechogenic). It was utilized a
      multi frequency linear probe (6-18 MHz). The patients were advised to avoid
      insulin injections on the areas with lipohypertrophy scanned by the ultrasound
      and the HbA1c changes were evaluated 3 months later. RESULTS: The
      lipohypertrophic areas presented at least three different aspects upon ultrasound
      assessment: the iso-hyperechogenic one, with a predominant fibrotic component;
      the isoechogenic one, with "large tangles" fibrotic elements and the iso
      hypoechogenic aspect with no fibrotic elements. When patients were advised to
      avoid insulin injections on areas with lipohypertrophy defined by ultrasound
      scan, 3 months after the first evaluation HbA1c had significantly improved (basal
      HbA1c 7.87 +/- 0.56 versus 7.67 +/- 0.52 3 months later, p = 0.029). No
      significant improvements of the HbA1c were found in the control matched group in
      which lipohypertrophy was only clinically valued through inspection and
      palpation. CONCLUSIONS: Ultrasound scan can help identify and characterize the
      lipohypertrophic areas and this might be useful to improve glycemic control.

PMID- 28452001
TI  - Development of a method of automated extraction of biological fingerprints from
      chest radiographs as preprocessing of patient recognition and identification.
AB  - This paper describes the development of an automated method of extraction of
      biological fingerprints (BFs), including detection of image orientation in chest
      radiographs. The image orientation of a target image was recognized and modified
      by examination of normalized cross-correlation values between a target image and
      averaged male and female images with correct image orientation. Templates of BFs
      were extracted from averaged images. Then, each BF in the target image was
      extracted from locations that showed the highest cross-correlation value between
      the template of BF in the averaged image and the corresponding BF in the target
      image. With our method, 100% (200/200) of image orientations were recognized
      correctly. If the orientation was recognized as inappropriate, our algorithm
      modified it into the appropriate chest image orientation. In addition, the BFs
      automatically extracted from target images were improved. This method would be
      useful in a preprocessing system for patient recognition and identification.

PMID- 28452002
TI  - Magnetization and demagnetization of magnetic dental attachments in a 3-T MRI
      system.
AB  - The purpose of this study was to evaluate the magnetization and demagnetization
      of magnetic dental attachments in a 3.0-T magnetic resonance imaging (MRI)
      scanner. A high-field-strength (3.0 T) MRI scanner (Achieva 3.0 T, Philips,
      Amsterdam, Netherlands) was used. Magnetic flux leakage was measured using a
      gaussmeter. To evaluate the magnetization and demagnetization of the magnetic
      assemblies and keepers caused by the moving in and out of the MRI scanner, the
      magnetic force of the attachments was measured before and after the table was
      moved in and out. Two settings were used wherein the magnetic assemblies and
      keepers were positioned on the table at angles of 0 degrees  or 90 degrees  with
      respect to the magnetic flux of the static magnetic field. The movement of the
      table was repeated 15 times. In addition, the retentive force of the magnetic
      dental attachments was measured after magnetic field exposure. The magnetic force
      of the magnetic attachments positioned at 0 degrees  decreased significantly
      after moving in and out of the MRI scanner (p < 0.05). In contrast, the magnetic
      force of the magnetic attachments positioned at 90 degrees  was stable after the
      movement of the table. The magnetic force of the keepers placed at both 0 degrees
      and 90 degrees  was slightly increased after the movement of the table. At 0
      degrees , the retentive force of the magnet-keeper combinations decreased when
      the magnetic assembly was exposed to the strong magnetic flux of the MRI scanner.
      Therefore, the removal of all removable magnetic dentures is recommended before
      an MRI examination.

PMID- 28452003
TI  - The Public Health Impact of the So-Called "Fluad Effect" on the 2014/2015
      Influenza Vaccination Campaign in Italy: Ethical Implications for Health-Care
      Workers and Health Communication Practitioners.
AB  - Seasonal influenza, causing complications, hospitalizations and deaths, generates
      a serious socio-economic burden, especially among elderly and high-risk subjects,
      as well as among adult individuals. Despite the availability and active free-of
      charge offer of influenza vaccines, vaccine coverage rates remain low and far
      from the target established by the Ministry of Health. Notwithstanding their
      effectiveness, vaccines are victims of prejudices and false myths, that
      contribute to the increasing phenomenon of vaccine hesitancy and loss of
      confidence. Media and, in particular, new media and information and communication
      technologies (ICTs) play a major role in disseminating health-related
      information. They are extremely promising devices for delivering health education
      and promoting disease prevention, including immunization. However, they can also
      have a negative impact on population's health attitudes and behaviors when
      channeling wrong, misleading information. During the 2014/2015 influenza
      vaccination campaign, the report of four deaths allegedly caused by
      administration of an adjuvanted influenza vaccine, Fluad - the so-called "Fluad
      case" - received an important media coverage, which contributed to the failure of
      the vaccination campaign, dramatically reducing the influenza vaccine uptake. In
      the extant literature, there is a dearth of information concerning the effect of
      the "Fluad case". The current study aims at quantifying the impact of the "Fluad
      effect" at the level of the Local Health Unit 3 (LHU3) ASL3 Genovese, Genoa,
      Italy. Ethical implications for health-care workers and health communication
      practitioners are also envisaged.

PMID- 28452005
TI  - Dual-isotope cardiac SPECT: the Twin Peaks Saga in nuclear cardiology.

PMID- 28452004
TI  - In vitro anticancer properties of selected Eucalyptus species.
AB  - In spite of the recent advancements in oncology, the overall survival rate for
      pancreatic cancer has not improved over the last five decades. Eucalypts have
      been linked with cytotoxic and anticancer properties in various studies; however,
      there is very little scientific evidence that supports the direct role of
      eucalypts in the treatment of pancreatic cancer. This study assessed the
      anticancer properties of aqueous and ethanolic extracts of four Eucalyptus
      species using an MTT assay. The most promising extracts were further evaluated
      using a CCK-8 assay. Apoptotic studies were performed using a caspase 3/7 assay
      in MIA PaCa-2 cells. The aqueous extract of Eucalyptus microcorys leaf and the
      ethanolic extract of Eucalyptus microcorys fruit inhibited the growth of
      glioblastoma, neuroblastoma, lung and pancreatic cancer cells by more than 80% at
      100 MUg/mL. The E. microcorys and Eucalyptus saligna extracts showed lower GI50
      values than the ethanolic Eucalyptus robusta extract in MIA PaCa-2 cells. Aqueous
      E. microcorys leaf and fruit extracts at 100 MUg/mL exerted significantly higher
      cell growth inhibition in MIA PaCa-2 cells than other extracts (p < 0.05).
      Statistically similar IC50 values (p > 0.05) were observed in aqueous E.
      microcorys leaf (86.05 +/- 4.75 MUg/mL) and fruit (64.66 +/- 15.97 MUg/mL) and
      ethanolic E. microcorys leaf (79.30 +/- 29.45 MUg/mL) extracts in MIA PaCa-2
      cells using the CCK-8 assay. Caspase 3/7-mediated apoptosis and morphological
      changes of cells were also witnessed in MIA PaCa-2 cells after 24 h of treatment
      with the extracts. This study highlighted the significance of E. microcorys as an
      important source of phytochemicals with efficacy against pancreatic cancer cells.
      Further studies are warranted to purify and structurally identify individual
      compounds and elucidate their mechanisms of action for the development of more
      potent and specific chemotherapeutic agents for pancreatic cancer.

PMID- 28452006
TI  - False-positive 13N-ammonia positron emission tomography perfusion scan caused by
      misalignment of adjacent lung activity during attenuation correction.

PMID- 28452007
TI  - LPS, Oleuropein and Blueberry extracts affect the survival, morphology and
      Phosphoinositide signalling in stimulated human endothelial cells.
AB  - Endothelial cells (EC) act as leading actors in angiogenesis. Understanding the
      complex network of signal transduction pathways which regulate angiogenesis might
      offer insights in the regulation of normal and pathological events, including
      tumours, vascular, inflammatory and immune diseases. The effects of olive oil and
      of Blueberry extracts upon the phosphoinositide (PI)-specific phospholipase C
      (PLC) enzymes were evaluated both in quiescent and inflammatory stimulated human
      umbilical vein EC (HUVEC) using molecular biology (multiliquid bioanalysis) and
      immunofluorescence techniques. Oleuropein significantly increased the number of
      surviving HUVEC compared to untreated controls, suggesting that it favours the
      survival and proliferation of EC. Our results suggest that Oleuropein might be
      useful to induce EC proliferation, an important event during angiogenesis, with
      special regard to wound healing. Blueberry extracts increased the number of
      surviving HUVEC, although the comparison to untreated controls did not result
      statistically significant. Lipopolysaccharide (LPS) administration significantly
      reduced the number of live HUVEC. LPS can also modify the expression of selected
      PLC genes. Adding Blueberry extracts to LPS treated HUVEC cultures did not
      significantly modify the variations of PLC expression induced by LPS. Oleuropein
      increased or reduced the expression of PLC genes, and statistically significant
      results were identified for selected PLC isoforms. Oleuropein also modified the
      effects of LPS upon PLC genes' expression. Thus, our results corroborate the
      hypothesis that Oleuropein owns anti-inflammatory activity. The intracellular
      localization of PLC enzymes was modified by the different treatments we used.
      Podosome-like structures were observed in differently LPS treated HUVEC.

PMID- 28452008
TI  - Underrepresentation of Hispanics and Other Minorities in Clinical Trials:
      Recruiters' Perspectives.
AB  - Clinical trials and research studies often fail to recruit participants from the
      minorities, hampering the generalizability of results. In order to mitigate this
      problem, the present study investigated how race/ethnicity affects the process of
      recruiting people from racial and ethnic minority groups, by conducting 11 focus
      groups with professional recruiters. Several themes emerged, such as how to adapt
      to potential participants' language competency and literacy levels, the
      importance to engage in culturally appropriate verbal and non-verbal
      communication, and to establish a sense of homophily between recruiters and
      patients. In addition, recruiters pointed out possible solutions to accommodate
      socioeconomic concerns, to adapt to contextual factors-including immigration
      status-and ultimately to respond to potential participants' mistrust of medical
      research. These findings are discussed, and future recommendations are provided.

PMID- 28452009
TI  - Detection of Potential Infectious Enteric Viruses in Fresh Produce by (RT)-qPCR
      Preceded by Nuclease Treatment.
AB  - Foodborne illnesses associated with contaminated fresh produce are a common
      public health problem and there is an upward trend of outbreaks caused by enteric
      viruses, especially human noroviruses (HNoVs) and hepatitis A virus (HAV). This
      study aimed to assess the use of DNase and RNase coupled to qPCR and RT-qPCR,
      respectively, to detect intact particles of human adenoviruses (HAdVs), HNoV GI
      and GII and HAV in fresh produce. Different concentrations of DNase and RNase
      were tested to optimize the degradation of free DNA and RNA from inactivated HAdV
      and murine norovirus (MNV), respectively. Results indicated that 10 ug/ml of
      RNase was able to degrade more than 4 log10 (99.99%) of free RNA, and 1 U of
      DNase degraded the range of 0.84-2.5 log10 of free DNA depending on the fresh
      produce analysed. The treatment with nucleases coupled to (RT)-qPCR was applied
      to detect potential infectious virus in organic lettuce, green onions and
      strawberries collected in different seasons. As a result, no intact particles of
      HNoV GI and GII were detected in the 36 samples analysed, HAdV was found in one
      sample and HAV was present in 33.3% of the samples, without any reasonable
      distribution pattern among seasons. In conclusion, RT-qPCR preceded by RNase
      treatment of eluted samples from fresh produce is a good alternative to detect
      undamaged RNA viruses and therefore, potential infectious viruses. Moreover, this
      study provides data about the prevalence of enteric viruses in organic fresh
      produce from Brazil.

PMID- 28452010
TI  - Occurrence and Trend of Hepatitis A Virus in Bivalve Molluscs Production Areas
      Following a Contamination Event.
AB  - The aim of this study was to assess the trend of hepatitis A virus (HAV) in a
      coastal zone impacted by a contamination event, providing data for the
      development of management strategies. A total of 352 samples, including four
      bivalve mollusc species (Mytilus galloprovincialis, Solen vagina, Venus gallina
      and Donax trunculus), were taken over a period of 6 months from 27 production
      areas of the coast and analysis were performed according to ISO/TS 15216-1:2013.
      HAV presence was detected in 77 samples from 11 production areas and all positive
      results were related to samples collected in the first 3 months of the
      surveillance, during which HAV prevalence was 39.9% and values as high as 5096
      genome copies/g were detected. A progressive reduction of viral contamination was
      evident during the first trimester of the monitoring, with prevalence decreasing
      from 78.8% in the first month, to 37.8% in the second and 3.9% in the third and
      quantitative levels reduced from an average value of 672 genome copies/g to 255
      genome copies/g over a period of 4 weeks (virus half-life: 21.5 days). A
      regression analysis showed that, during the decreasing phase of the
      contamination, the data fitted a reciprocal quadratic model (Ra2 = 0.921) and,
      based on the model, a residual presence of HAV could be estimated after
      negativization of the production areas. The statistical analysis of the results
      per shellfish species and per production area showed that there were limited
      differences in contamination prevalence and levels among diverse bivalve species,
      while a statistically significant difference was present in quantitative levels
      of one production area. These data could be useful for the development of both
      risk assessment models and code of practice for the management of viral
      contamination in primary production.

PMID- 28452011
TI  - Molecular cloning and characterization of a halotolerant alpha-amylase from
      marine metagenomic library derived from Arabian Sea sediments.
AB  - Functional screening of a metagenomic library of marine sediment revealed an
      amylolytic clone BTM109. This report states the purification and characterization
      of a moderately halotolerant alpha-amylase, with more than 51% activity in 2.5 M
      NaCl. The molecular mass of purified protein was determined to be 55.7 kDa by
      MALDI-TOF MS. The optimum pH for enzyme activity was pH 7 and temperature for
      maximal activity was 40  degrees C. At 5 mM concentration, Ca2+ enhanced the
      enzyme activity indicating that the enzyme is a Ca2+ dependent alpha-amylase
      which was confirmed by the starch hydrolysis pattern using TLC. These physico
      chemical properties support the suitability of this enzyme for various industrial
      applications.

PMID- 28452012
TI  - Isolation, cloning, and characterization of a cuticle collagen gene, Mi-col-5, in
      Meloidogyne incognita.
AB  - Cuticle collagens form a major part of the nematode cuticle and are responsible
      for maintaining the overall shape of the animal and its protection from the
      external environment. Although substantial research on cuticle collagen genes has
      been carried out in Caenorhabditis elegans, their isolation and characterization
      in plant parasitic nematodes have been limited to a few genes only. In this
      study, a cuticle collagen gene, Mi-col-5, was isolated from root-knot nematode,
      Meloidogyne incognita. A partial segment of 402 bp was first cloned and analyzed
      on Gbrowse followed by subsequent cloning of the 1047 bp long full cDNA
      specifying the open reading frame. The deduced amino acid sequence showed 92%
      sequence identity with that of Mj-col-5. However, a transmembrane helix was
      predicted in Mi-col-5 which was not present in Mj-col-5. The conserved pattern of
      cysteine residues in Mi-col-5 suggested that it belonged to group 2 of nematode
      cuticle collagens but with a longer carboxy terminal region as was the case with
      Mj-col-5. Domain prediction revealed the presence of a nematode cuticle collagen
      N terminal domain and a pfam collagen domain along with collagen triple helix
      repeats. A phylogenetic tree based on the amino acid sequences showed
      evolutionary relationship of Mi-col-5 with cuticle collagens genes of other
      nematodes. 3D models for Mi-col-5 were predicted with the best confidence score
      of -2.78. Expression of Mi-col-5 transcript was found to be maximum in egg masses
      followed by adult females and J2s suggesting its role in the early stages of the
      development of the nematode during its life cycle.

PMID- 28452013
TI  - Effects of salt and heat pre-treatment factors on efficient regeneration in
      barley (Hordeum vulgare L.).
AB  - An efficient callus induction and plant regeneration system has been developed
      using salt and heat as pre-treatment factors for three barley genotypes viz. BB
      3, BB-6 and BHL-18. Different concentrations of NaCl (1.5, 2.5, 3.5, 4.5, 5.5 and
      6.5 g/L) were used and its effects were determined on the basis of the viability
      of callus (CV), plant regeneration (PR), relative growth rate (RGR) and tolerance
      index (TI). The BB-6 showed highest performance on tolerance based on CV
      (14.72%), PR (7.69%), RGR (0.91%) and TI (0.42%) at 6.5 g/L NaCl. Various NaCl
      concentrations displayed significantly differences at P < 0.01 level as compared
      with the control. Plant regeneration capability was recorded after heat pre
      treatment using calli at 30, 35 and 40  degrees C. In this study, BHL-18 produced
      highest callus induction (59.71%) after desiccated at 40  degrees C for BB-6.
      Highest regeneration was recorded around 41.66% when 4 weeks old calli were pre
      treated at 35  degrees C. Furthermore, heat pre-treatment factors were very
      effective for enhancing plant regeneration (25-41.66%) which was 1.8-2.14 fold
      higher compared to the control (13.88-19.44%). Hence, heat treated calli
      displayed higher tolerance level to survive in NaCl-induced treatment for
      determining abiotic stress and increased regeneration rate at 35  degrees C
      temperature in BB-6 barley genotype.

PMID- 28452014
TI  - A review on chimeric xylanases: methods and conditions.
AB  - Multi-functional enzymes are one of the nature's solutions to facilitate
      metabolic pathways, thus several reactions are regulated and performed
      simultaneously on one polypeptide chain. Inspired by nature, artificial chimeric
      proteins have been designed to reduce the production costs and improve the
      performance. One of the interesting applications of this method is in the plant
      based industries such as feed additive, waste treatment, biofuel production, and
      pulp and paper bleaching. In fact, the heterogeneous texture of plants needs
      using a combination of different enzymes to achieve an optimal quality in the
      manufacturing process. Given that xylans are the most abundant non-cellulosic
      polysaccharides in nature, xylanases are widely utilized in the mentioned
      industries. In this regard, several studies have been conducted to develop the
      relevant chimeric enzymes. Despite the successes that have been attained in this
      field, misfolding, functional or structural interference, and linker breakage
      have been reported in some cases. The present paper reviews the research to
      introduce the prerequisites to design an appropriate chimeric xylanase.

PMID- 28452015
TI  - Biodegradation of ciprofloxacin by white rot fungus Pleurotus ostreatus.
AB  - Unrestricted and reckless use of antibiotics has resulted in their accumulation
      in environment. This, in turn, has led to the emergence of multiple drug
      resistant microbes. The present study focuses on degradation of ciprofloxacin
      (CIP) by an edible white rot fungus Pleurotus ostreatus. Effect of CIP was
      determined on radial growth and biomass of P. ostreatus. Titrimetric and
      spectrophotometric assays were carried out to assess the degrading potential of
      P. ostreatus towards CIP. It was found that CIP has a stimulatory effect on
      growth and enzyme activity of P. ostreatus. Maximum enzyme (glucanase,
      ligninases, laccase) production was observed at the highest concentration of CIP
      (500 ppm). Antibiotic degradation of about 68.8, 94.25 and 91.34% was estimated
      after 14 days of incubation at 500 ppm CIP using Titrimetric, Indigo carmine and
      Methyl orange assay, respectively. Degradation of CIP was further validated by
      high performance liquid chromatography (HPLC) and microbiological analysis. HPLC
      analysis revealed 95.07% degradation while microbiological test also exhibited a
      decreased antimicrobial activity of degraded products against Escherichia coli,
      Staphylococcus aureus and Streptococcus pyogenes. To the best of our knowledge,
      this is the first study wherein P. ostreatus was used for the degradation of
      ciprofloxacin.

PMID- 28452016
TI  - Assessment of genetic diversity in Costus pictus accessions based on RAPD and
      ISSR markers.
AB  - Costus pictus, belonging to the family Costaceae, is one of the valuable
      medicinal plants with its anti-diabetic property. Despite ever-increasing demand
      from the pharmaceutical industry, this species is being less exploited at
      molecular level. Hence, an effort has been made in the present study to
      characterize the 15 accessions of C. pictus collected from different geographical
      regions of India through random amplified polymorphic DNA (RAPD) and inter-simple
      sequence repeats (ISSR) markers. A total of 25 RAPD and 20 ISSR primers were used
      in the present study. The RAPD analysis generated 343 loci, of which 124 were
      polymorphic with an average of 4.96 loci per primer. While, ISSR primers produced
      177 loci, of which 77 were polymorphic with an average of 3.85 loci per primer.
      The similarity coefficients ranged from 0.86-0.99, 0.84-0.95 and 0.86-0.96 for
      RAPD, ISSR and combined RAPD-ISSR, respectively. The UPGMA dendrogram generated
      using these data showed low level of divergence among the accessions from South
      and West regions. Further, accession-specific bands were also revealed by RAPD
      and ISSR markers which might be contributed to specific trait. This investigation
      was an understanding of genetic variation within the C. pictus accessions. The
      present finding indicates that both the marker tools RAPD and ISSR combined or
      individually can be used in determining the genetic relationship between the
      accessions. It may be concluded that data of hereditary differences appeared
      among the C. pictus accessions could be utilized for their conservation and
      reproducing programs.

PMID- 28452017
TI  - Green synthesis of silver oxide nanoparticles and its antibacterial activity
      against dental pathogens.
AB  - In the present study, the use of silver oxide nanoparticles (Ag2O NPs)
      synthesized using Ficus benghalensis prop root extract (FBPRE) as a reducing and
      stabilizing agent is reported and evaluated for its antibacterial activity
      against dental bacterial strains. The effects of pH, extract concentration, metal
      ion concentration, and contact time were studied to confirm the optimum
      production of Ag2O NPs. Our results suggest that, by increasing the extract
      concentration and the time frame, there will be a significant increase in the
      formation of nanoparticles. The UV-vis adsorption spectra show the absorbance
      peak in the range of 430 nm, and FTIR spectral peaks indicate that the
      phytochemicals in the extract are responsible for the formation of the
      nanoparticles. The HR-TEM image, SAED, and XRD pattern confirmed the morphology
      (spherical), silver oxide 42.7 nm and silver 51.4 nm, and crystalline nature of
      the obtained nanoparticles, respectively. The blend of FBPRE and Ag2O NPs showed
      excellent antibacterial activities against the two-dental bacteria Streptococcus
      mutans and Lactobacilli sp. The study results suggest that the blend of
      synthesized Ag2O NPS and FBPRE will be useful in tooth paste as a germicidal
      agent after extensive investigation with animal models.

PMID- 28452018
TI  - Elucidate genetic diversity and population structure of Olea europaea L.
      germplasm in Iran using AFLP and IRAP molecular markers.
AB  - Currently, study of the inter and the intra-population genetic disparity was done
      by use of the 200 Olea europaea L. which is found growing naturally in the nation
      of Iran, and this study was carried out by AFLP and IRAP markers. The
      fingerprints that were similar to the AFLP and the IRAP markers were evidence of
      high concentrations of heterozygosity and this shows that O. europaea L. is
      primarily the out crossing species. The average percentage of polymorphism is as
      shown below: 87.15 and 87.38% of the information used in regard to the AFLP and
      the IRAP, respectively. The gene disparity numerals on the population researched
      were 1.087 for HT and 0.871 for HS in regard to AFLP. For the IRAP it was 1.084
      for HT and 0.860 for HS. The general values for genetic variations that are found
      in the O. europaea L. germplasm in the nation of Iran were then assessed through
      putting together the AFLP and the IRAP information so as to cover a larger
      genome. Arguing from the AFLP and the IRAP studies, it can be concluded that
      there are more levels of genetic variation at inter and the intra-population
      level for the O. europaea.

PMID- 28452019
TI  - Structure and function of seed storage proteins in faba bean (Vicia faba L.).
AB  - The protein subunit is the most important basic unit of protein, and its study
      can unravel the structure and function of seed storage proteins in faba bean. In
      this study, we identified six specific protein subunits in Faba bean (cv. Qinghai
      13) combining liquid chromatography (LC), liquid chromatography-electronic spray
      ionization mass (LC-ESI-MS/MS) and bio-information technology. The results
      suggested a diversity of seed storage proteins in faba bean, and a total of 16
      proteins (four GroEL molecular chaperones and 12 plant-specific proteins) were
      identified from 97-, 96-, 64-, 47-, 42-, and 38-kD-specific protein subunits in
      faba bean based on the peptide sequence. We also analyzed the composition and
      abundance of the amino acids, the physicochemical characteristics, secondary
      structure, three-dimensional structure, transmembrane domain, and possible
      subcellular localization of these identified proteins in faba bean seed, and
      finally predicted function and structure. The three-dimensional structures were
      generated based on homologous modeling, and the protein function was analyzed
      based on the annotation from the non-redundant protein database (NR database,
      NCBI) and function analysis of optimal modeling. The objective of this study was
      to identify the seed storage proteins in faba bean and confirm the structure and
      function of these proteins. Our results can be useful for the study of protein
      nutrition and achieve breeding goals for optimal protein quality in faba bean.

PMID- 28452020
TI  - Pectin from muskmelon (Cucumis melo var. reticulatus) peels: extraction
      optimization and physicochemical properties.
AB  - Pectin derived from plant waste sources is currently focused as an economical and
      eco-friendly approach. Optimization of pectin extraction from muskmelon peel by
      response surface methodology (RSM) was investigated in this study. Box-Behnken
      Design (BBD) was used to identify the optimal level of the extraction variables
      such as time, pH and temperature. A second-order model equation for pectin
      extraction was obtained from multiple regression analysis of experimental data
      with the correlation coefficient (R 2) value of 0.92. ANOVA results showed that
      linear effect of temperature and combined effect of pH with temperature were
      found significant for pectin extraction from muskmelon peel. Validation results
      had good agreement with the predicted results. Pectin extracted from muskmelon
      peel was classed as high methoxy pectin with the equivalent weight of 384.5
      g/mol. Non-newtonian pseudoplastic flow behaviour was observed for muskmelon
      pectin from the viscosity studies.

PMID- 28452021
TI  - Biodegradation of thermally treated low density polyethylene by fungus Rhizopus
      oryzae NS 5.
AB  - Polythene is considered as one of the important object used in daily life. Being
      versatile in nature and resistant to microbial attack, they effectively cause
      environmental pollution. In the present study, biodegradation of low-density
      polyethylene (LDPE) have been performed using fungal lab isolate Rhizopus oryzae
      NS5. Lab isolate fungal strain capable of adhering to LDPE surface was used for
      the biodegradation of LDPE. This strain was identified as Rhizopus oryzae NS5
      (Accession No. KT160362). Fungal growth was observed on the surface of the
      polyethylene when cultured in potato dextrose broth at 30  degrees C and 120 rpm,
      for 1 month. LDPE film was characterized before and after incubation by Fourier
      transform infrared spectroscopy, scanning electron microscopy, atomic force
      microscopy and universal tensile machine. About 8.4 +/- 3% decrease
      (gravimetrically) in weight and 60% reduction in tensile strength of polyethylene
      was observed. Scanning electron microscope analysis showed hyphal penetration and
      degradation on the surface of polyethylene. Atomic force microscope analysis
      showed increased surface roughness after treatment with fungal isolate. A thick
      network of fungal hyphae forming a biofilm was also observed on the surface of
      the polyethylene pieces. Present study shows the potential of Rhizopus oryzae NS5
      in polyethylene degradation in eco friendly and sustainable manner.

PMID- 28452022
TI  - Xylitol production from non-detoxified and non-sterile lignocellulosic
      hydrolysate using low-cost industrial media components.
AB  - Immobilized Candida tropicalis cells in freeze dried calcium alginate beads were
      used for production of xylitol from lignocellulosic waste like corn cob
      hydrolysate without any detoxification and sterilization of media. Media
      components for xylitol fermentation were screened by statistical methods. Urea,
      KH2PO4 and initial pH were identified as significant variables by Plackett-Burman
      (PB) design. Significant medium components were optimized by response surface
      methodology (RSM). Predicted xylitol yield by RSM model and experimental yield
      was 0.87 and 0.79 g/g, respectively. Optimized conditions (urea 1.5 g/L, KH2PO4
      1.9 g/L, xylose 55 g/L, pH 6.7) enhanced xylitol yield by 32% and xylose
      consumption by twofold over those of basal media. In addition, the immobilized
      cells were reused five times at shake flask level with optimized medium without
      affecting the xylitol productivity and yield. Xylitol production was successfully
      scaled up to 7.5 L stirred tank reactor using optimized media. Thus, the
      optimized condition with non-detoxified pentose hydrolysate from corn cob
      lignocellulosic waste with minimal nutrients without any sterilization opens up
      the scope for commercialization of the process.

PMID- 28452023
TI  - Enhanced degradation of polyhydroxyalkanoates (PHAs) by newly isolated
      Burkholderia cepacia DP1 with high depolymerase activity.
AB  - The contribution of microbial depolymerase has received much attention because of
      its potential in biopolymer degradation. In this study, the P(3HB) depolymerase
      enzyme of a newly isolated Burkholderia cepacia DP1 from soil in Penang,
      Malaysia, was optimized using response surface methodology (RSM). The factors
      affecting P(3HB) depolymerase enzyme production were studied using one-variable
      at-a-time approach prior to optimization. Preliminary experiments revealed that
      the concentration of nitrogen source, concentration of carbon source, initial pH
      and incubation time were among the main factors influencing the enzyme
      productivity. An increase of 9.4 folds in enzyme production with an activity of
      5.66 U/mL was obtained using optimal medium containing 0.028% N of di-ammonium
      hydrogen phosphate and 0.31% P(3HB-co-21%4HB) as carbon source at the initial pH
      of 6.8 for 38 h of incubation. Moreover, the RSM model showed great similarity
      between predicted and actual enzyme production indicating a successful model
      validation. This study warrants the ability of P(3HB) degradation by B. cepacia
      DP1 in producing higher enzyme activity as compared to other P(3HB) degraders
      being reported. Interestingly, the production of P(3HB) depolymerase was rarely
      reported within genus Burkholderia. Therefore, this is considered to be a new
      discovery in the field of P(3HB) depolymerase production.

PMID- 28452024
TI  - Total phenolics, antioxidant, antitumor, and enzyme inhibitory activity of Indian
      medicinal and aromatic plants extracted with different extraction methods.
AB  - The phenolic content, antioxidant, antitumor, and enzyme inhibitory activities of
      commonly used medicinal herbs from a Unani system of medicine were investigated
      using four different extraction methods. Among the plants studied, the Hyssopus
      officinalis L, Origanum vulgare L, and Portulaca oleracea L. extracts showed the
      highest amount of total phenolics (64.40, 60.35, and 58.81 mg GAE/g) and revealed
      significant antioxidant activities. The plants also showed a maximum cytotoxic
      activity as indicated by H. officinalis (82%), O. vulgare (75%), and P. oleracea
      (72%) showed more than 70% cytotoxicity for breast cancer cells, 82% of the cells
      were dead at the concentration of 500 mg/mL. The plants H. officinalis, P.
      oleracea, O. vulgare, and Rubia cordifolia L. revealed more than 80% inhibition
      towards xanthine oxidase and comprising maximum 70% of inhibition for superoxide
      dismutase. From results we conclude that there is a strong correlation between
      phenolic content, antioxidant, and enzyme inhibitory activity among these plants,
      indicating phenolics are the major compounds for these biological activities.
      Furthermore, this study provides the basis for the therapeutic importance of
      studied plants as latent inhibitors of oxidative stress and antitumor cell
      proliferation which correlate with the ethnobotanical data contained in the Unani
      system of medicine.

PMID- 28452025
TI  - Improving Cancer Literacy for the Deaf Using Deaf-Tailored Educational
      Interventions: a Review of the Literature.
AB  - To date, there have been many strategies, including educational interventions,
      for cancer prevention and control, but most of them are not deaf-tailored ones.
      This narrative review aimed to examine cancer educational programs to improve the
      deaf individuals' knowledge and attitude toward cancer. The design of this study
      is a narrative review. We searched ISI Web of Science, Scopus, Science Direct,
      and MEDLINE/PubMed using the following search strategy: ("cancer education" AND
      "deaf") OR ("cancer" AND "deaf" AND literacy). Publication years ranged from 1983
      to 2016 for studies on cancer educational interventions for the deaf. Included
      studies were analyzed regarding research methodologies, types of intervention,
      and major findings. In total, 12 included studies were classified into three
      research methodologies. Although short-term and long-term knowledge improvement
      has been reported, since there is limited evidence on the types of cancer-related
      educational interventions and there are insufficient studies, longterm
      effectiveness of educations in improving cancer knowledge of the deaf has to be
      reported cautiously. Current deaf-tailored education interventions are limited,
      but included functional features which facilitate communicating cancer health
      information to the deaf community. In fact, cancer literacy might improve
      considering deaf community preferences such as using a short open caption, sign
      language, and plain language in educational interventions, but further research
      is recommended.

PMID- 28452026
TI  - Micro-sized TiO2 as photoactive catalyst coated on industrial porcelain gres
      tiles to photodegrade drugs in water.
AB  - Pharmaceutical compounds and their metabolites raise worrying questions because
      of their continuous release and lack of efficient removal by conventional
      wastewater treatments; therefore, they are being detected in groundwater, surface
      water and drinking water in increasing concentrations. Paracetamol and aspirin
      are two of the most commonly used drugs employed as fever reducer, analgesic and
      anti-inflammatory. They and their metabolites are very often found in river
      water, so their degradation is necessary in order to render water suitable for
      human consumption. The present work is focused on the comparison of the
      photocatalytic performance of industrial active gres porcelain tiles covered with
      a commercial micro-sized TiO2 by industrial process using either conventional
      spray deposition or innovative digital printing methods. The photodegradation of
      two commonly used drugs, namely aspirin and paracetamol, was investigated both
      individually and as a mixture, in both deionized and tap water. The results
      reveal the full conversion of the drugs and the significant role of the
      photocatalytic tiles in the mineralization processes leading to harmless
      inorganic species. In particular, the digitally printed tiles exhibited better
      photodegradation performance for both drugs compared to the spray deposited
      tiles. No deactivation was observed on both photocatalytic tiles.

PMID- 28452027
TI  - Development of a mechanistic model for prediction of CO2 capture from gas
      mixtures by amine solutions in porous membranes.
AB  - A mechanistic model was developed in order to predict capture and removal of CO2
      from air using membrane technology. The considered membrane was a hollow-fiber
      contactor module in which gas mixture containing CO2 was assumed as feed while 2
      amino-2-metyl-1-propanol (AMP) was used as an absorbent. The mechanistic model
      was developed according to transport phenomena taking into account mass transfer
      and chemical reaction between CO2 and amine in the contactor module. The main aim
      of modeling was to track the composition and flux of CO2 and AMP in the membrane
      module for process optimization. For modeling of the process, the governing
      equations were computed using finite element approach in which the whole model
      domain was discretized into small cells. To confirm the simulation findings,
      model outcomes were compared with experimental data and good consistency was
      revealed. The results showed that increasing temperature of AMP solution
      increases CO2 removal in the hollow-fiber membrane contactor.

PMID- 28452028
TI  - Effects of silver nanowire length and exposure route on cytotoxicity to
      earthworms.
AB  - To accurately evaluate the environmental toxicity of silver nanowires (AgNWs), it
      is necessary to characterize how the cytotoxicity of these nanomaterials is
      affected by the route of exposure. However, few studies have addressed the
      exposure route or mechanism of toxicity of nanomaterials, particularly of
      nanowires, in living organisms. In this study, we therefore analyzed the main
      exposure route of AgNWs in vitro, using earthworms (Eisenia andrei) as a model
      system, via flow cytometry. We subsequently examined the in vivo toxicity of
      AgNWs to earthworms in soil. These tests revealed that intracellular esterase
      activity was correlated with adsorption of the nanowires to the surfaces of
      coelomocytes in vitro, and that in vivo cytotoxicity resulted mainly from oral,
      rather than dermal, exposure to the nanowires. Overall, shorter AgNWs (10 MUm)
      were more toxic than longer AgNWs (20 MUm). To our knowledge, this study is the
      first report regarding the ecotoxicity of nanowires to earthworms in soil. Our
      findings provide important information to help assess the risk of toxic AgNW
      contamination of soil ecosystems.

PMID- 28452029
TI  - Phosphorus removal from aqueous solution in parent and aluminum-modified
      eggshells: thermodynamics and kinetics, adsorption mechanism, and diffusion
      process.
AB  - Parent and aluminum-modified eggshells were prepared and characterized with X-ray
      diffraction, specific surface area measurements, infrared spectroscopy, zeta
      potential, and scanning electron microscope, respectively. Besides, phosphorus
      adsorptions in these two eggshells at different temperatures and solution pH were
      carried out to study adsorption thermodynamics and kinetics as well as the
      mechanisms of phosphorus adsorption and diffusion. The results indicated that
      high temperature was favorable for phosphorus adsorption in parent and aluminum
      modified eggshells. Alkaline solution prompted phosphorus adsorption in parent
      eggshell, while the maximum adsorption amount was achievable at pH 4 in aluminum
      modified eggshell. Adsorption isotherms of phosphorus in these eggshells could be
      well described by Langmuir and Freundlich models. Phosphorus adsorption amounts
      in aluminum-modified eggshell were markedly higher compared to those in parent
      eggshell. Adsorption heat indicated that phosphorus adsorption in parent eggshell
      was a typically physical adsorption process, while chemical adsorption mechanism
      of ion exchange between phosphorus and hydroxyl groups on the surface of
      eggshells was dominated in aluminum-modified eggshell. The time-resolved uptake
      curves showed phosphorus adsorption in aluminum-modified eggshell was
      significantly faster than that in parent eggshell. Moreover, there existed two
      clear steps in time-resolved uptake curves of phosphorus in parent eggshell.
      Based on pseudo-second order kinetic model and intraparticle diffusion model, we
      inferred more than one process affected phosphorus adsorption. The first process
      was the diffusion of phosphorus through water to external surface and the opening
      of pore channel in the eggshells, and the second process was mainly related to
      intraparticle diffusion.

PMID- 28452030
TI  - The effects and the toxicity increases caused by bicarbonate, chloride, and other
      water components during the UV/TiO2 degradation of oxazaphosphorine drugs.
AB  - The influences of HCO3-, Cl-, and other components on the UV/TiO2 degradation of
      the antineoplastic agents ifosfamide (IFO) and cyclophosphamide (CP) were studied
      in this work. The results indicated that the presence of HCO3-, Cl-, NO3-, and
      SO42- in water bodies resulted in lower degradation efficiencies. The half-lives
      of IFO and CP were 1.2 and 1.1 min and increased 2.3-7.3 and 3.2-6.3 times,
      respectively, in the presence of the four anions (initial compound concentration
      = 100 MUg/L, TiO2 loading =100 mg/L, anion concentration = 1000 mg/L, and pH =
      8). Although the presence of HCO3- in the UV/TiO2/HCO3- system resulted in a
      lower degradation rate and less byproduct formation for IFO and CP, two newly
      identified byproducts, P11 (M.W. = 197) and P12 (M.W. = 101), were formed and
      detected, suggesting that additional pathways occurred during the reaction of
      *CO3- in the system. The results also showed that *CO3- likely induces a
      preferred ketonization pathway. Besides the inorganic anions HCO3-, Cl-, NO3-,
      and SO42-, the existence of dissolved organic matter in the water has a
      significant effect and inhibits CP degradation. Toxicity tests showed that higher
      toxicity occurred in the presence of HCO3- or Cl- during UV/TiO2 treatment and
      within 6 h of reaction time, implying that the effects of these two anions should
      not be ignored when photocatalytic treatment is applied to treat real wastewater.

PMID- 28452031
TI  - Evaluating health risks posed by heavy metals to humans consuming blood cockles
      (Anadara granosa) from the Upper Gulf of Thailand.
AB  - There is global concern about heavy metal contamination in the environment.
      Adverse health effects can be caused by heavy metals in contaminated food and
      water. Therefore, environmental monitoring studies and risk assessments should be
      conducted periodically. In this study, we measured levels of Cd, Cr, Cu, Hg, Mn,
      Ni, Pb, and Zn in blood cockles (Anadara granosa) collected from three locations
      in the Upper Gulf of Thailand. Hazard quotients and hazard indices were
      calculated to evaluate the health risks posed by heavy metals in consumed blood
      cockles. Heavy metal concentrations in all of the blood cockle samples were lower
      than the relevant food standards. The hazard quotients and hazard indices were <1
      in all three sampling areas, indicating that adverse health effects were not
      likely to be caused by exposure to heavy metals in blood cockles over a human
      lifetime.

PMID- 28452033
TI  - Carbon dioxide emissions, output, and energy consumption categories in Algeria.
AB  - This study examines the relation between CO2 emissions, income, non-renewable,
      and renewable energy consumption in Algeria during the period extending from 1980
      to 2011. Our work gives particular attention to the validity of environmental
      Kuznets curve (EKC) hypothesis. The autoregressive distributed lag (ARDL) with
      break point method outcome demonstrates the positive effect of non-renewable type
      of energy on CO2 emissions consumption. On the contrary, the results reveal an
      insignificant effect of renewable energy on environment improvement. Moreover,
      the results accept the existence of EKC hypothesis but the highest gross domestic
      product value in logarithm scale of our data is inferior to the estimated turning
      point. Consequently, policy-makers in Algeria should expand the ratio of
      renewable energy and should decrease the quota of non-renewable energy
      consumption.

PMID- 28452032
TI  - Mixture risk assessment due to ingestion of arsenic, copper, and zinc from
      milkfish farmed in contaminated coastal areas.
AB  - Human health risks associated with the consumption of metal-contaminated fish
      over extended periods have become a concern particularly in Taiwan, where fish is
      consumed on a large scale. This study applied the interaction-based hazard index
      (HI) to assess the mixture health risks for fishers and non-fishers who consume
      the arsenic (As), copper (Cu), and zinc (Zn) contaminated milkfish from As
      contaminated coastal areas in Taiwan, taking into account joint toxic actions and
      potential toxic interactions. We showed that the interactions of As-Zn and Cu-Zn
      were antagonistic, whereas As-Cu interaction was additive. We found that HI
      estimates without interactions considered were 1.3-1.6 times higher than
      interactive HIs. Probability distributions of HI estimates for non-fishers were
      less than 1, whereas all 97.5%-tile HI estimates for fishers were >1. Analytical
      results revealed that the level of inorganic As in milkfish was the main
      contributor to HIs, indicating a health risk posed to consumers of fish farmed in
      As-contaminated areas. However, we found that Zn supplementation could
      significantly decrease As-induced risk of hematological effect by activating a Zn
      dependent enzyme. In order to improve the accuracy of health risk due to exposure
      to multiple metals, further toxicological data, regular environmental monitoring,
      dietary survey, and refinement approaches for interactive risk assessment are
      warranted.

PMID- 28452034
TI  - Deciphering biodegradable chelant-enhanced phytoremediation through microbes and
      nitrogen transformation in contaminated soils.
AB  - Biodegradable chelant-enhanced phytoremediation offers an alternative treatment
      technique for metal contaminated soils, but most studies to date have addressed
      on phytoextraction efficiency rather than comprehensive understanding of the
      interactions among plant, soil microbes, and biodegradable chelants. In the
      present study, we investigated the impacts of biodegradable chelants, including
      nitrilotriacetate, S,S-ethylenediaminedisuccinic acid (EDDS), and citric acid on
      soil microbes, nitrogen transformation, and metal removal from contaminated
      soils. The EDDS addition to soil showed the strongest ability to promote the
      nitrogen cycling in soil, ryegrass tissue, and microbial metabolism in comparison
      with other chelants. Both bacterial community-level physiological profiles and
      soil mass specific heat rates demonstrated that soil microbial activity was
      inhibited after the EDDS application (between day 2 and 10), but this effect
      completely vanished on day 30, indicating the revitalization of microbial
      activity and community structure in the soil system. The results of quantitative
      real-time PCR revealed that the EDDS application stimulated denitrification in
      soil by increasing nitrite reductase genes, especially nirS. These new findings
      demonstrated that the nitrogen release capacity of biodegradable chelants plays
      an important role in accelerating nitrogen transformation, enhancing soil
      microbial structure and activity, and improving phytoextraction efficiency in
      contaminated soil.

PMID- 28452035
TI  - Extensive review of shale gas environmental impacts from scientific literature
      (2010-2015).
AB  - Extensive reviews and meta-analyses are essential to summarize emerging
      developments in a specific field and offering information on the current trends
      in the scientific literature. Shale gas exploration and exploitation has been
      extensively debated in literature, but a comprehensive review of recent studies
      on the environmental impacts has yet to be carried out. Therefore, the goal of
      this article is to systematically examine scientific articles published between
      2010 and 2015 and identify recent advances and existing data gaps. The examined
      articles were classified into six main categories (water resources, atmospheric
      emissions, land use, induced seismicity, occupational and public health and
      safety, and other impacts). These categories are analyzed separately to identify
      specific challenges, possibly existing consensus and data gaps yet remained in
      the literature.

PMID- 28452036
TI  - Role of EGFR as prognostic factor in head and neck cancer patients treated with
      surgery and postoperative radiotherapy: proposal of a new approach behind the
      EGFR overexpression.
AB  - In an era of personalized treatment, there is a great interest in identifying
      factors which might predict patient response to radiotherapy (RT). The role of
      epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma
      (HNSCC) remains still controversial. We performed a retrospective analysis on the
      prognostic value of EGFR in HNSCC patients treated with surgery and postoperative
      RT through a semiquantitative immunohistochemical analysis of EGFR membrane
      expression. We retrospectively analyzed 65 HNSCC patients treated in our
      Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median
      follow-up was 43.5 months (range 0.2-173 months). None of these patients were
      treated with postoperative concomitant chemotherapy. Tumor samples were obtained
      from surgical specimens. Membrane features (intensity, extension) of EGFR
      expression were evaluated, and a statistical analysis (univariate and
      multivariate) was conducted to correlate these parameters with overall survival
      (OS) and disease-free survival (DFS). Patients with an intense and complete
      labeling of EGFR presented worse OS and DFS compared with groups obtained by all
      other possible combination, and the difference was borderline statistically
      significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification
      of patients was performed considering EGFR expression on the tumor tissue and
      classifying its distribution as "homogeneous" or "heterogeneous." We found that
      patients showing an "heterogeneous" EGFR expression distribution had worse OS and
      DFS compared to the "homogeneous" group of patients. Based on our results, EGFR
      expression, especially referring to membrane features (semiquantitative
      analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC
      treated with surgery and adjuvant RT. Prospective trials could be useful to
      confirm the prognostic role of EGFR expression and also to assess a predictive
      role to select that might benefit from more aggressive treatments.

PMID- 28452037
TI  - Need for new review of article on ketogenic dietary regimes for cancer patients.

PMID- 28452039
TI  - Erratum to: Efficacy of Zofenopril vs. Irbesartan in Combination with a Thiazide
      Diuretic in Hypertensive Patients with Multiple Risk Factors not Controlled by a
      Previous Monotherapy: A Review of the Double-Blind, Randomized "Z" Studies.

PMID- 28452038
TI  - Is Next-Generation Sequencing the way to go for Residual Disease Monitoring in
      Acute Lymphoblastic Leukemia?
AB  - Minimal residual disease (MRD) is the most important independent prognostic
      factor in acute lymphoblastic leukemia (ALL). Since it has been implemented into
      in treatment stratification strategies, cure rates have improved significantly
      for all age groups. Real time quantitative (RQ)-PCR of clonal immunoglobulin and
      T-cell receptor gene rearrangements using allele-specific primers is currently
      regarded as the gold standard for MRD analysis in ALL, as it is not only highly
      sensitive and specific but also provides accurate MRD quantification. Following
      recent advances in next-generation sequencing (NGS), much attention has been
      devoted to the development of NGS-based MRD assays. This new technique can
      enhance sensitivity provided that sufficient numbers of cells are analyzed.
      Recent reports have shown that NGS-MRD also tends to be more specific for relapse
      prediction than RQ-PCR. In addition, NGS provides information on the
      physiological B- and T-cell repertoire during and after treatment, which has been
      shown to be prognostically relevant. However, before implementation of NGS-MRD
      detection in clinical practice, several issues must be addressed and the whole
      workflow needs to be standardized, including not only the analytical phase (spike
      in calibrators, quality controls) but also the pre-analytical (e.g. sample
      preparation) and the post-analytical phases (e.g. bioinformatics pipeline,
      guidelines for correct data interpretation). These topics are currently addressed
      by a European network, the EuroClonality-NGS Consortium. In conclusion, NGS is a
      promising tool for MRD detection with the potential to overcome most of the
      limitations of RQ-PCR and to become the new gold standard for MRD detection in
      ALL.

PMID- 28452040
TI  - Biocatalytic activity of Monascus mycelia depending on physiology and high
      sensitivity to product concentration.
AB  - Cell suspension culture using mycelia as whole cell biocatalyst for production of
      orange Monascus pigments has been carried out successfully in a nonionic
      surfactant micelle aqueous solution. Thus, selection of mycelia as whole cell
      biocatalyst and the corresponding enzymatic kinetics for production of orange
      Monascus pigments can be optimized independently. Mycelia selected from submerged
      culture in a nonionic surfactant micelle aqueous solution with low pH 2.5
      exhibits robust bioactivity. At the same time, enzymatic kinetic study shows that
      the bioactivity of mycelia as whole cell biocatalyst is sensitive to high product
      concentration. Segregation of product from mycelia by cell suspension culture in
      a nonionic surfactant micelle aqueous solution or peanut oil-water two-phase
      system is not only necessary for studying the enzymatic kinetics but also
      beneficial to industrial application of mycelia as whole cell biocatalyst.

PMID- 28452041
TI  - Cloning and characterization of the Type I Baeyer-Villiger monooxygenase from
      Leptospira biflexa.
AB  - Baeyer-Villiger monooxygenases are recognized by their ability and high
      selectivity as oxidative biocatalysts for the generation of esters or lactones
      using ketones as starting materials. These enzymes represent valuable tools for
      biooxidative syntheses since they can catalyze reactions that otherwise involve
      strong oxidative reagents. In this work, we present a novel enzyme, the Type I
      Baeyer-Villiger monooxygenase from Leptospira biflexa. This protein is
      phylogenetically distant from other well-characterized BVMOs. In order to study
      this new enzyme, we cloned its gene, expressed it in Escherichia coli and
      characterized the substrate scope of the Baeyer-Villiger monooxygenase from L.
      biflexa as a whole-cell biocatalyst. For this purpose, we performed the screening
      of a collection of ketones with variable structures and sizes, namely acyclic
      ketones, aromatic ketones, cyclic ketones, and fused ketones. As a result, we
      observed that this biocatalyst readily oxidized linear- and branched- medium
      chain ketones, alkyl levulinates and linear ketones with aromatic substituents
      with excellent regioselectivity. In addition, this enzyme catalyzed the oxidation
      of 2-substituted cycloketone derivatives but showed an unusual selection against
      substituents in positions 3 or 4 of the ring.

PMID- 28452042
TI  - What should I expect from my recalled Adept Hip Resurfacing?
AB  - "My Hip Resurfacing (HR) has been recalled. What will happen to me?" This is the
      question of every patient who underwent an implant recall, a highly stressful
      event for both patients and physicians. Triggered by a 11.64% failure rate at 7
      years, a recall process started for Adept HR with head diameter less than 48 mm.
      We report our experience in the recall process of 40 patients with the above
      mentioned components. One patient underwent revision surgery due to an adverse
      reaction to metal debris at 5-year follow-up. None of the patients were scheduled
      for revision, with an estimated survival rate of 97.6% at 7 years. Implants were
      well positioned with an average acetabular inclination angle of 37 degrees .
      Cobalt and chromium blood levels were below the safety threshold of clinical
      relevance. Functional scores were excellent. In the case of a well-positioned
      device with normal ion levels, a good performance of the implant is generally
      observed. Even if we experienced a very low revision rate, this may certainly get
      worse over time since not all possible failures are predictable, thus requiring a
      careful periodic follow-up.

PMID- 28452043
TI  - Comparison of clinical results and patient's satisfaction between direct anterior
      approach and Hardinge approach in primary total hip arthroplasty in a community
      hospital.
AB  - INTRODUCTION: Aim of the study is to compare clinical results and patient's
      satisfaction between direct anterior approach and Hardinge approach in primary
      total hip arthroplasty. METHODS: A group of 30 patients operated with DAA (group
      B) were compared to 39 patients operated by Hardinge approach (group A). Peri-
      and postoperative complications, Harris Hip Score (HHS), implant positioning,
      experienced pain and patient satisfaction were evaluated at a mean follow-up of
      30 months. RESULTS: HHS at follow-up was significantly better in group B (92.2 +/
      11.9 vs 95.2 +/- 4.5 p = 0.04 Student's t test). There was no difference in
      femoral stem positioning while cup inclination was significantly better in group
      B (40.6 degrees  +/- 6.6 degrees  vs 44.3 degrees  +/- 7.9 degrees , p = 0.04
      Student's t test). Overall pain recalled by patients was significantly lower in
      group B. CONCLUSION: The introduction of DAA does not affect patients' final
      outcome but comes with comparable functional recovery and greater patient
      satisfaction.

PMID- 28452044
TI  - Implementation and process evaluation of three interventions to promote screening
      mammograms delivered for 4 years in a large primary care population.
AB  - The optimal form of outreach to promote repeated, on time screening mammograms in
      primary care has not been established. The purpose of this study is to assess the
      implementation process and process outcomes for three interventions for promoting
      biannual screening mammography in a randomized trial. In a large urban primary
      care practice over a 4-year period, we randomized women aged 40-85 and eligible
      for mammograms to three interventions: reminder letter only (LO), reminder letter
      + reminder call (RC), and reminder letter + counseling call (CC). We tracked
      information system development, staff training, patient and provider recruitment,
      reach, dose delivered and received, fidelity, and context measures. Ninety-three
      of 95 providers approved participation by 80% (23,999) of age-eligible patients,
      of whom only 207 (0.9%) opted not to receive any intervention. Of 9161 initial
      reminder letters mailed to women coming due or overdue for mammograms, 0.8% were
      undeliverable. Of women in the RC and CC arms unresponsive to the first reminder
      letter (n = 3982), 71.4% were called and reached, and of those, 49.1% scheduled a
      mammogram. Only 33.4% of women reached in the CC arm received full counseling,
      and women in the CC arm were less likely to schedule a mammogram than those in
      the RC arm. Implementing mail and telephone mammography reminders is feasible and
      acceptable in a large urban practice and reaches a majority of patients. Many
      schedule a mammogram when reached. A reminder letter followed by a simple
      reminder call if needed may be the optimal approach to promoting screening
      mammograms.

PMID- 28452045
TI  - Toxicity of malathion at early life stages of the Senegalese sole, Solea
      senegalensis (Kaup, 1858): notochord and somatic disruptions.
AB  - The toxicity of malathion to Solea senegalensis was studied in a static renewal
      bioassay for 24, 48 and 72 h, with toxicant concentrations ranging from 1.56
      until 100 ugL-1. The LC50 values of malathion for 48 and 72 h was 63.5 (95% C.I:
      50.83-79.34) and 22.94 (95% C.I: 17.16-30.68) ugL-1 respectively. The survival of
      larvae was non-affected by exposure to malathion at concentrations up to 25 ugL-1
      (24 h NOEC), 6.25 ugL-1 (48 h NOEC) and <1.6 ug-1 (72 h NOEC). At the end of the
      experiment, surviving larvae from concentrations smaller than the 72h-LC50 were
      chosen to study morphological changes during malathion exposure. Results revealed
      a strong disruption in the notochord and trunk musculature integrity as a result
      of toxicant exposure. Noticeable changes in the composition and reduction of
      collagen fibers from the perinotochordal connective sheath and perimysium were
      clearly detected. The trunk musculature was also altered, showing a general
      disorganization of fibers. Moreover, malathion exposure provoked pericardial and
      yolk-sac oedemas and histopathological alterations in some other organ- systems
      and tissues (i.e. liver, pancreas, intestine).

PMID- 28452046
TI  - Employment as a measure of participation in adults with cerebral palsy.

PMID- 28452047
TI  - The importance of topographically corrected null models for analyzing ecological
      point processes.
AB  - Analyses of point process patterns and related techniques (e.g., MaxEnt) make use
      of the expected number of occurrences per unit area and second-order statistics
      based on the distance between occurrences. Ecologists working with point process
      data often assume that points exist on a two-dimensional x-y plane or within a
      three-dimensional volume, when in fact many observed point patterns are generated
      on a two-dimensional surface existing within three-dimensional space. For many
      surfaces, however, such as the topography of landscapes, the projection from the
      surface to the x-y plane preserves neither area nor distance. As such, when these
      point patterns are implicitly projected to and analyzed in the x-y plane, our
      expectations of the point pattern's statistical properties may not be met. When
      used in hypothesis testing, we find that the failure to account for the
      topography of the generating surface may bias statistical tests that incorrectly
      identify clustering and, furthermore, may bias coefficients in inhomogeneous
      point process models that incorporate slope as a covariate. We demonstrate the
      circumstances under which this bias is significant, and present simple methods
      that allow point processes to be simulated with corrections for topography. These
      point patterns can then be used to generate "topographically corrected" null
      models against which observed point processes can be compared.

PMID- 28452048
TI  - Artificial light at night alters trophic interactions of intertidal
      invertebrates.
AB  - Despite being globally widespread in coastal regions, the impacts of light
      pollution on intertidal ecosystems has received little attention. Intertidal
      species exhibit many night-time-dependent ecological strategies, including
      feeding, reproduction, orientation and predator avoidance, which are likely
      negatively affected by shifting light regimes, as has been observed in
      terrestrial and aquatic taxa. Coastal lighting may shape intertidal communities
      through its influence on the nocturnal foraging activity of dogwhelks (Nucella
      lapillus), a widespread predatory mollusc that structures biodiversity in
      temperate rocky shores. In the laboratory, we investigated whether the basal and
      foraging activity of this predator was affected by exposure to night-time
      lighting both in the presence and absence of olfactory predator cues (Carcinus
      maenas, common shore crab). Assessments of dogwhelks' behavioural responses to
      night-time white LED lighting were performed on individuals that had been
      acclimated to night-time white LED lighting conditions for 16 days and
      individuals that had not previously been exposed to artificial light at night.
      Dogwhelks acclimated to night-time lighting exhibited natural refuge-seeking
      behaviour less often compared to control animals, but were more likely to respond
      to and handle prey irrespective of whether olfactory predator cues were present.
      These responses suggest night-time lighting likely increased the energetic demand
      of dogwhelks through stress, encouraging foraging whenever food was available,
      regardless of potential danger. Contrastingly, whelks not acclimated under night
      time lighting were more likely to respond to the presence of prey under
      artificial light at night when olfactory predator cues were present, indicating
      an opportunistic shift towards the use of visual instead of olfactory cues in
      risk evaluation. These results demonstrate that artificial night-time lighting
      influences the behaviour of intertidal fauna such that the balance of
      interspecific interactions involved in community structuring may be affected.

PMID- 28452049
TI  - Stepfamilies Doing Family: A Meta-Ethnography.
AB  - The present review examines how stepfamily members without a shared history co
      construct a shared family identity and what family processes are relevant in this
      stepfamily formation. Three databases (Web of Science, PsycInfo, and ProQuest)
      were systematically searched, resulting in 20 included qualitative studies. The
      meta-ethnography approach of Noblit and Hare allowed synthesizing these
      qualitative studies and constructing a comprehensive framework of stepfamilies
      doing family. Three interdependent family tasks were identified: (a) honoring the
      past, (b) marking the present, and (c) investing in the future. Stepfamily
      members' experiences of these family tasks are strongly affected by the dominant
      societal perspectives and characterized by an underlying dialectical tension
      between wanting to be like a first-time family and feeling the differences in
      their family structure at the same time. These findings clearly demonstrate the
      family work that all stepfamily members undertake and provide a broader context
      for interpreting stepfamilies' co-construction of a new family identity.

PMID- 28452050
TI  - In vivo muscle behaviour in cerebral palsy with an equinus gait: are we on track?

PMID- 28452051
TI  - Increased productivity in wet years drives a decline in ecosystem stability with
      nitrogen additions in arid grasslands.
AB  - Adding nutrients to nutrient-limited ecosystems typically lowers plant diversity
      and decreases species asynchrony. Both, in turn, decrease the stability of
      productivity in the response to negative climate fluctuations such as droughts.
      However, most classic studies examining stability have been done in relatively
      wet grasslands dominated by perennial grasses. We examined how nutrient additions
      influence the stability of productivity to rainfall variability in an arid
      grassland with a mix of perennial and annual species. Of the nutrients, only
      nitrogen increased productivity, and only in wet years. In addition, only
      nitrogen decreased the stability of productivity. Thus, nutrient addition makes
      ecosystem productivity less stable in both wet and arid grasslands. However, the
      mechanism is very different. In contrast to wet grasslands, adding nitrogen to an
      arid grassland did not decrease diversity. Rather, stability decreased with
      nitrogen addition due to an increase in annual species that increased
      productivity. In other words, in our arid grassland, nitrogen addition decreased
      ecosystem stability because of increased ecosystem responsiveness to positive
      climate fluctuations. These climate fluctuations were facilitated by annual
      species that take advantage of wet years and can escape dry years as seeds. Our
      data support the conclusion that nutrient additions decrease the stability of
      productivity in both wet and arid grasslands. Nutrient enrichment increases the
      sensitivity of productivity to low rainfall years in wet grasslands, whereas
      nutrient enrichment in arid grasslands increases the sensitivity of productivity
      to high rainfall years.

PMID- 28452052
TI  - Computation of ancestry scores with mixed families and unrelated individuals.
AB  - The issue of robustness to family relationships in computing genotype ancestry
      scores such as eigenvector projections has received increased attention in
      genetic association, and is particularly challenging when sets of both unrelated
      individuals and closely related family members are included. The current standard
      is to compute loadings (left singular vectors) using unrelated individuals and to
      compute projected scores for remaining family members. However, projected
      ancestry scores from this approach suffer from shrinkage toward zero. We consider
      two main novel strategies: (i) matrix substitution based on decomposition of a
      target family-orthogonalized covariance matrix, and (ii) using family-averaged
      data to obtain loadings. We illustrate the performance via simulations, including
      resampling from 1000 Genomes Project data, and analysis of a cystic fibrosis
      dataset. The matrix substitution approach has similar performance to the current
      standard, but is simple and uses only a genotype covariance matrix, while the
      family-average method shows superior performance. Our approaches are accompanied
      by novel ancillary approaches that provide considerable insight, including
      individual-specific eigenvalue scree plots.

PMID- 28452053
TI  - Patterns of care and predictors of adjuvant therapies in elderly patients with
      glioblastoma: An analysis of the National Cancer Data Base.
AB  - BACKGROUND: The objectives of this study were to characterize patterns of care
      and to identify predictors for adjuvant therapy in elderly patients with
      glioblastoma in the modern era. METHODS: The National Cancer Data Base was
      queried for patients aged 70 years and older with glioblastoma diagnosed from
      January 1, 2004 through December 31, 2012. Multinomial logistic regression was
      used to identify predictors for receiving adjuvant therapy. Survival outcomes
      were estimated using the Kaplan-Meier method and were analyzed using Cox
      regression models and the log-rank test. RESULTS: In total, 14,886 patients were
      identified. Of these, 8214 patients (55.2%) received combined-modality therapy
      with chemotherapy and radiation (CRT), 3955 (26.6%) received no adjuvant therapy,
      2065 (13.9%) received radiation therapy (RT) alone, and 652 (4.4%) received
      chemotherapy (CT) alone after undergoing resection. The receipt of CRT increased
      in frequency over the study interval, from 40.3% in 2004 to 59.8% in 2012.
      Younger patients (ages 70-75 years) were more likely to receive CRT than no
      adjuvant therapy (P < .0001 for all other age groups) or adjuvant RT alone (P <
      .0001 for all other age groups). Combined-modality therapy with adjuvant CRT
      produced improved survival outcomes, and the highest median overall survival was
      9.2 months. CONCLUSIONS: In this analysis of elderly patients who had
      glioblastoma diagnosed from 2004 through 2012, a significant increase in the
      receipt of combined-modality therapy was observed. Combined-modality treatment
      produces improved survival outcomes and should be considered as adjuvant
      treatment for carefully selected elderly patients. Cancer 2017;123:3277-84. (c)
      2017 American Cancer Society.

PMID- 28452054
TI  - Comparing outcomes of matched related donor and matched unrelated donor
      hematopoietic cell transplants in adults with B-Cell acute lymphoblastic
      leukemia.
AB  - BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) using human
      leukocyte antigen (HLA)-matched related donors (RDs) and allogeneic HCT using HLA
      matched unrelated donors (URDs) produce similar outcomes for patients with acute
      myelogenous leukemia, whereas the donor source has been reported to be a
      predictor of outcomes in myelodysplastic syndrome. METHODS: Post-HCT outcomes for
      1458 acute lymphoblastic leukemia patients from 2000 to 2011 were analyzed, and
      RD and URD transplants were compared. RESULTS: The median age was 37 years
      (range, 18-69 years). In the multivariate analysis, HLA 8/8 allele-matched URD
      recipients had similar transplant-related mortality (TRM) and all-cause mortality
      in comparison with RD recipients (hazard ratios [HRs], 1.16 [95% confidence
      interval (CI), 0.91-1.48] and 1.01 [95% CI, 0.85-1.19], respectively); 7/8 URD
      recipients had a greater risk of TRM and all-cause mortality in comparison with
      RD recipients (HRs, 1.92 [95% CI, 1.47-2.52] and 1.29 [95% CI, 1.05-1.58],
      respectively). The risk of TRM and all-cause mortality was also greater for 7/8
      URD recipients versus 8/8 URD recipients. Compared with RD recipients, both 8/8
      and 7/8 URD recipients had a lower risk of relapse (HRs, 0.77 [95% CI, 0.62-0.97]
      and 0.75 [95% CI, 0.56-1.00], respectively). Both 8/8 and 7/8 URD recipients had
      a greater risk of acute graft-versus-host disease (GVHD; HRs, 2.18 [95% CI, 1.76
      2.70] and 2.65 [95% CI, 2.06-3.42], respectively) and chronic GVHD (HRs, 1.28
      [95% CI, 1.06-1.55] and 1.46 [95% CI, 1.14-1.88], respectively) in comparison
      with RD recipients. CONCLUSIONS: In the absence of RD transplantation, 8/8 URD
      transplantation is a viable alternative with similar survival outcomes, whereas
      7/8 URD transplantation is associated with poorer overall survival. Cancer
      2017;123:3346-55. (c) 2017 American Cancer Society.

PMID- 28452055
TI  - Anthropogenic spreading of anguillid herpesvirus 1 by stocking of infected farmed
      European eels, Anguilla anguilla (L.), in the Schlei fjord in northern Germany.
AB  - The Schlei fjord in northern Germany is the recipient water of a comprehensive
      eel, Anguilla anguilla (L.), stocking programme. Since 2015, stocked eels become
      alizarin red S marked, but to date no control mechanism is implemented in this
      stock enhancement measure to prevent anthropogenic spreading of diseases.
      Consequentially, it was possible that farmed stocking cohorts of 2015 and 2016
      (in total ca. 1040 kg) were subsequently tested positive for anguillid
      herpesvirus 1 (AngHV 1). For this study, 100 eels [total length (TL) 24.3-72.9
      cm, age ca. 1-6 years] were caught in 2016 and investigated with regard to AngHV
      1 infection, parasite load (Anguillicoloides crassus) and body conditions. 68% of
      the eels were found to be virus positive while larger specimens were more often
      infected. In addition, a fitted generalized linear model (area under the curve =
      0.741) demonstrated that an increase in individual TL is accompanied with an
      increased risk of clinically relevant virus loads. Anguillicoloides crassus
      turned out to be an important stressor for eels, because parasite and virus load
      revealed a significant positive correlation. The results of this study evidently
      show the urgent need of a disease containment strategy for eel stocking
      programmes.

PMID- 28452056
TI  - Outbreak of Cleidodiscus in juvenile black crappies (Pomoxis nigromaculatus) and
      bath treatment with praziquantel.

PMID- 28452057
TI  - Alternative splicing switches: Important players in cell differentiation.
AB  - Alternative splicing (AS) greatly expands the coding capacities of genomes by
      allowing the generation of multiple mature mRNAs from a limited number of genes.
      Although the massive switch in AS profiles that often accompanies variations in
      gene expression patterns occurring during cell differentiation has been
      characterized for a variety of models, their causes and mechanisms remain largely
      unknown. Here, we integrate foundational and recent studies indicating the AS
      switches that govern the processes of cell fate determination. We include some
      distinct AS events in pluripotent cells and somatic reprogramming and discuss new
      progresses on alternative isoform expression in adipogenesis, myogenic
      differentiation and stimulation of immune cells. Finally, we cover novel insights
      on AS mechanisms during neuronal differentiation, paying special attention to the
      role of chromatin structure.

PMID- 28452058
TI  - Barley transcriptome analyses upon interaction with different aphid species
      identify thionins contributing to resistance.
AB  - Aphids are phloem-feeding insects that cause yield loss on a wide range of crops,
      including cereals such as barley. Whilst most aphid species are limited to one or
      few host species, some are able to reproduce on many plants belonging to
      different families. Interestingly, aphid probing behaviour can be observed on
      both host and non-host species, indicating that interactions take place at the
      molecular level that may impact host range. Here, we aimed to gain insight into
      the interaction of barley with aphid species differing in their ability to infest
      this crop by analysing transcriptional responses. Firstly, we determined
      colonization efficiency, settlement and probing behaviour for the aphid species
      Rhopalosiphum padi, Myzus persicae and Myzus cerasi, which defined host, poor
      host and non-host interactions, respectively. Analyses of barley transcriptional
      responses revealed gene sets differentially regulated upon the different barley
      aphid interactions and showed that the poor-host interaction with M. persicae
      resulted in the strongest regulation of genes. Interestingly, we identified
      several thionin genes strongly up-regulated upon interaction with M. persicae,
      and to a lesser extent upon R. padi interaction. Ectopic expression of two of
      these genes in Nicotiana benthamiana reduced host susceptibility to M. persicae,
      indicating that thionins contribute to defences against aphids.

PMID- 28452059
TI  - Arrhenius equation modeling for the shelf life prediction of tomato paste
      containing a natural preservative.
AB  - BACKGROUND: The shelf life of tomato paste with microencapsulated olive leaf
      extract was compared with that of samples containing a commercial preservative by
      accelerated shelf life testing. Based on previous studies showing that olive leaf
      extract as a rich source of phenolic compounds can have antimicrobial properties,
      application of its encapsulated form to improve the storage stability of tomato
      paste is proposed here. RESULTS: Regarding total soluble solids, the control and
      the sample containing 1000 ug g-1 sodium benzoate had the lowest (Q10  = 1.63)
      and highest (Q10  = 1.88) sensitivity to temperature changes respectively; also,
      the microencapsulated sample containing 1000 ug g-1 encapsulated olive leaf
      extract (Q10  = 1.83) followed the sample containing 1000 ug g-1 sodium benzoate
      in terms of the highest kinetic rates. In the case of consistency, the lowest and
      highest activation energies (Ea ) corresponded to samples containing 1000 ug g-1
      non-encapsulated olive leaf extract and 1000 ug g-1 microencapsulated olive leaf
      extract respectively. CONCLUSION: Interestingly, samples containing
      microencapsulated olive leaf extract could maintain the original quality of the
      tomato paste very well, while those with non-encapsulated olive leaf extract
      rated the worst performance (among all specimens) in terms of maintaining their
      quality indices for a long time period. Overall, the shelf life equation was able
      to predict the consistency index of all tomato paste samples during long-time
      storage with high precision. (c) 2017 Society of Chemical Industry.

PMID- 28452060
TI  - CiMYB17, a stress-induced chicory R2R3-MYB transcription factor, activates
      promoters of genes involved in fructan synthesis and degradation.
AB  - In Cichorium intybus, inulin metabolism is mediated by fructan-active enzymes
      (FAZYs): sucrose:sucrose 1-fructosyltransferase (1-SST), fructan:fructan 1
      fructosyltransferase (1-FFT), and fructan 1-exohydrolases 1, 2a and 2b (1-FEH1, 
      2a and -2b), respectively. While these enzymes have been rigorously
      characterized, the transcriptional network orchestrating their development- and
      stress-related expression has remained largely unknown. Here, the possible role
      of R2R3-MYB transcription factors in FAZY regulation was explored via
      bioinformatic identification of R2R3-MYBs (using an RNA sequencing (RNAseq)
      database), studies of co-expression of these factors with target genes, in vivo
      transient transactivation assays of FAZY target promoters (dual luciferase
      assay), and a yeast one-hybrid assay investigating the specificity of the binding
      of these factors to cis-elements. The chicory MYB transcription factor CiMYB17
      specifically activated promoters of 1-SST and 1-FFT by binding to the consensus
      DNA-motif DTTHGGT. Unexpectedly, CiMYB17 also activated promoters of fructan
      exohydrolase genes. The stimulatory effect on promoter activities of sucrose
      transporter and cell wall invertase genes points to a general role in regulating
      the source-sink relationship. Co-induction of CiMYB17 with 1-SST and 1-FFT (and,
      less consistently, with 1-FEH1/2) in nitrogen-starved or abscisic acid (ABA)
      treated chicory seedlings and in salt-stressed chicory hairy roots supports a
      role in stress-induced fructan metabolism, including de novo fructan synthesis
      and trimming of pre-existing fructans, whereas the reduced expression of CiMYB17
      in developing taproots excludes a role in fructan accumulation under normal
      growth conditions.

PMID- 28452061
TI  - Evaluation of real-life dosing of oral medicines with respect to fluid and food
      intake in a Dutch-speaking population.
AB  - WHAT IS KNOWN AND OBJECTIVE: Oral drug administration is the most preferred route
      of drug administration. For some specific classes of drugs, recommendations
      regarding the intake of the drug product are provided by and approved in the
      summary of product characteristics (SmPC) after testing the oral drug product in
      clinical trials under strict and predefined conditions. The aim of this study was
      to investigate how certain classes of medicines are taken in a "real-life"
      setting in terms of concomitant fluid and food intake by a Dutch-speaking
      population in Flanders (Belgium). The outcome of this study was comprehensively
      discussed with literature data to evaluate the positive or negative consequences
      of their drug intake in daily life. METHODS: A retrospective and non
      interventional study was set up by means of questionnaires completed by two
      different groups: children (ie 0-15 years) and (young) adults (ie 16 years and
      older). RESULTS AND DISCUSSION: In children, the co-administered volume increases
      with age because of a gradual switch from liquids to solid dosage forms. In
      adults, water was the most selected co-administered fluid and the preferred
      volume of intake was a half glass of liquid. WHAT IS NEW AND CONCLUSION: Results
      of the surveys clearly indicated that the majority of all participants took their
      medication with a sip or half glass of water. However, this was not the case for
      the youngest children, as their preferred formulations were liquids (eg
      solutions, suspensions) which do not require any extra intake of liquid. In the
      case of specific classes of drugs, real-life intake can still be improved,
      suggesting that the pharmacist's advice has an important influence on their
      administration of medicines.

PMID- 28452062
TI  - Support provided by nurses to parents of hospitalized children - cultural
      adaptation and validation of Nurse Parent Support Tool and initial research
      results.
AB  - INTRODUCTION: Child's illness and hospitalisation are difficult and stressful
      situations both for the patients themselves and for their parents. Supporting the
      ill child and their guardians is an indispensable element of caring for ill
      children. The Nurse-Parent Support Model developed by Margaret Miles is based on
      four elements, namely emotional support, appraisal support, informational support
      and instrumental support. AIM: The aim of the research was (i) cultural
      adaptation and validation of The Nurse-Parent Support Tool into Polish and (ii)
      initial assessment of parents' perception of nursing support given to the parents
      of children hospitalised in five paediatric wards in Poland. MATERIAL AND METHOD:
      Quantitative cross-sectional study was conducted in a group of 195 parents of
      children hospitalised in five different hospital wards in eastern Poland. RESULTS
      AND CONCLUSIONS: Theoretical validity of the four-factor version of NPST is
      proved by the correlation matrix analysis and inter-correlation between the
      dimensions of the described tool as well as the analysis of the internal
      structure of the test verified on the basis of its internal validity which also
      confirms its reliability. However, theoretical validity of the test is not
      confirmed by the factor analysis whose results indicate that the tool encompasses
      two factors that explain 58.5% of variances. Respondents rated instrumental
      support provided by the nurses the highest, appraisal and informational support
      were rated slightly lower, and emotional support was rated the lowest. Negative
      correlation between the level of stress and emotional support (r = -0.35),
      informational support (r = -0.29) and support in general (r = -0.30) was
      demonstrated. Polish four-factor version of NPST is recommended only for
      international comparative analyses, whereas the use of two-factor version of NPST
      is recommended for national research programmes. The level of support given to
      the parents of children hospitalised in Poland seems to be unsatisfactory.

PMID- 28452064
TI  - Mortality of necrotizing fasciitis: relative influence of individual and hospital
      level factors, a nationwide multilevel study, France, 2007-12.
AB  - BACKGROUND: Necrotizing soft-tissue infections (NSTI) are rare, life-threatening
      conditions. OBJECTIVES: To assess whether admitting hospital characteristics were
      associated with NSTI mortality. METHODS: We studied the French nationwide
      hospital discharge database (retrospective national cohort). All patients
      admitted in the period 2007-12 with an International Classification of Diseases
      10 code of necrotizing fasciitis were eligible. We extracted data on the patients
      (age, sex, intensive care unit admission, comorbidities) and hospitals (public
      vs. private proprietary; for public hospitals, teaching, yes/no; and number of
      NSTI admissions, >= 3 NSTI cases/year, yes/no). Multivariable analyses were
      performed to identify independent predictors of 28-day mortality and in-hospital
      mortality using mixed logistic regression and Cox proportional hazards models,
      respectively. RESULTS: We identified 1537 patients (915 males) with a median age
      of 60 years (interquartile range 48-75), admitted to 326 hospitals, public (82%)
      and admitting < 3 NSTI cases/year (93%). Overall, 364 patients died [23.7%; 95%
      confidence interval (CI) 21.6-25.9]. Patients treated in public teaching centres
      with >= 3 NSTI cases annually had lower 28-day mortality (adjusted odds ratio
      0.68; 95% CI 0.46-0.99; P = 0.045) and in-hospital mortality rates than patients
      treated in local hospitals, even after adjusting for potentially relevant
      individual risk factors. No significant association was found between mortality
      and interhospital transfer. CONCLUSIONS: Our findings highlight an increased
      survival in teaching centres with high-volume NSTI procedures. If confirmed in
      other settings, these findings reinforce the importance of expertise in early
      diagnosis and management of this condition.

PMID- 28452063
TI  - Risk factors of adverse health outcomes after hospital discharge modifiable by
      clinical pharmacist interventions: a review with a systematic approach.
AB  - The present review assessed the evidence on risk factors for the occurrence of
      adverse health outcomes after discharge (i.e. unplanned readmission or adverse
      drug event after discharge) that are potentially modifiable by clinical
      pharmacist interventions. The findings were compared with patient characteristics
      reported in guidelines that supposedly indicate a high risk of drug-related
      problems. First, guidelines and risk assessment tools were searched for patient
      characteristics indicating a high risk of drug-related problems. Second, a
      systematic PubMed search was conducted to identify risk factors significantly
      associated with adverse health outcomes after discharge that are potentially
      modifiable by a clinical pharmacist intervention. After the PubMed search, 37
      studies were included, reporting 16 risk factors. Only seven of 34 patient
      characteristics mentioned in pertinent guidelines corresponded to one of these
      risk factors. Diabetes mellitus (n = 11), chronic obstructive lung disease (n =
      9), obesity (n = 7), smoking (n = 5) and polypharmacy (n = 5) were the risk
      factors reported most frequently in the studies. Additionally, single studies
      also found associations of adverse health outcomes with different drug classes
      {e.g. warfarin [hazard ratio 1.50; odds ratio (OR) 3.52], furosemide [OR 2.25] or
      high beta-blocker starting doses [OR 3.10]}. Although several modifiable risk
      factors were found, many patient characteristics supposedly indicating a high
      risk of drug-related problems were not part of the assessed risk factors in the
      context of an increased risk of adverse health outcomes after discharge.
      Therefore, an obligatory set of modifiable patient characteristics should be
      created and implemented in future studies investigating the risk for adverse
      health outcomes after discharge.

PMID- 28452065
TI  - Trabecular resorption patterns of cement-bone interlock regions in total knee
      replacements.
AB  - : With in vivo service, there is loss of mechanical interlock between trabeculae
      and PMMA cement in total knee replacements. The mechanisms responsible for the
      loss of interlock are not known, but loss of interlock results in weaker cement
      bone interfaces. The goal of this study was to determine the pattern of
      resorption of interdigitated bone using a series of 20 postmortem retrieved knee
      replacements with a wide range of time in service (3-22 years). MicroCT scans
      were obtained of a segment of the cement-bone interface below the tibial tray for
      each implant. Image processing methods were used to determine interface
      morphology and to identify supporting, interdigitated, resorbed, and isolated
      bone as a function of axial position. Overall, the amount of remaining
      interdigitated bone decreased with time in service (p = 0.0114). The distance
      from the cement border (at the extent of cement penetration into the bone bed) to
      50% of the interdigitated volume decreased with time in service (p = 0.039).
      Isolated bone, when present, was located deep in the cement layer. Overall,
      resorption appears to start at the cement border and progresses into the cement
      layer. Initiation of trabecular resorption near the cement border may be a
      consequence of proximity to osteoclastic cells in the adjacent marrow space.
      CLINICAL SIGNIFICANCE: Aseptic loosening of joint replacements remains an
      important clinical problem. This work explores the process and pattern of
      trabecular bone resorption responsible for loss of interface fixation. (c) 2017
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      35:2773-2780, 2017.

PMID- 28452066
TI  - Inhibition of transmembrane member 16A calcium-activated chloride channels by
      natural flavonoids contributes to flavonoid anticancer effects.
AB  - BACKGROUND AND PURPOSE: Natural flavonoids are ubiquitous in dietary plants and
      vegetables and have been proposed to have antiviral, antioxidant, cardiovascular
      protective and anticancer effects. Transmembrane member 16A (TMEM16A)-encoded
      Ca2+ -activated Cl- channels play a variety of physiological roles in many organs
      and tissues. Overexpression of TMEM16A is also believed to be associated with
      cancer progression. Therefore, inhibition of TMEM16A current may be a potential
      target for cancer therapy. In this study, we screened a broad spectrum of
      flavonoids for their inhibitory activities on TMEM16A currents. EXPERIMENTAL
      APPROACH: A whole-cell patch technique was used to record the currents. The BrdU
      assay and transwell technique were used to investigate cell proliferation and
      migration. KEY RESULTS: At a concentration of 100 MUM, 10 of 20 compounds caused
      significant (>50%) inhibition of TMEM16A currents. The four most potent compounds
      - luteolin, galangin, quercetin and fisetin - had IC50 values ranging from 4.5 to
      15 MUM). To examine the physiological relevance of these findings, we also
      studied the effects of these flavonoids on endogenous TMEM16A currents in
      addition to cell proliferation and migration in LA795 cancer cells. Among the
      flavonoids tested, we detected a highly significant correlation between TMEM16A
      current inhibition and cell proliferation or reduction of migration. CONCLUSIONS
      AND IMPLICATIONS: This study demonstrates that flavonoids inhibit TMEM16A
      currents and suggests that flavonoids could have anticancer effects via this
      mechanism.

PMID- 28452067
TI  - Zinc monotherapy for young children with presymptomatic Wilson disease: A
      multicenter study in Japan.
AB  - BACKGROUND AND AIM: Few studies of zinc monotherapy for presymptomatic Wilson
      disease have focused on young children. We therefore evaluated long-term efficacy
      and safety of zinc monotherapy for such children and established benchmarks for
      maintenance therapy. METHODS: We retrospectively and prospectively examined
      children under 10 years old with presymptomatic Wilson disease who received zinc
      monotherapy from time of diagnosis at 12 participating pediatric centers in
      Japan. RESULTS: Twenty-four patients met entry criteria. Aspartate
      aminotransferase and alanine aminotransferase decreased significantly beginning 1
      month after initiation of treatment and usually remained under 50 U/L from 1 to 8
      years of treatment. Twenty four-hour urinary copper decreased significantly at 6
      months and usually remained under 75 MUg/day and between 1 and 3 MUg/kg/day for
      the remainder of the study. All patients continued to take zinc, and none became
      symptomatic. In patients under 6 years old who received 50 mg/day of zinc as an
      initial dose, aspartate aminotransferase and alanine aminotransferase
      significantly decreased at 1 month after initiation of treatment, as did gamma
      glutamyltransferase and 24-h urinary copper at 6 months. CONCLUSIONS: To our
      knowledge, this is the first multicenter study of zinc monotherapy for young
      children with presymptomatic Wilson disease. Such monotherapy proved highly
      effective and safe. Maintaining normal transaminase values (or values under 50
      U/L when normalization is difficult) and 24-h urinary copper excretion between 1
      and 3 MUg/kg/day and under 75 MUg/day is a reasonable goal. An initial dose of 50
      mg/day is appropriate for patients under 6 years old.

PMID- 28452068
TI  - An evaluation of vitamin D levels in children with seasonal allergic rhinitis
      during pollen season.
AB  - BACKGROUND: Serum vitamin D levels have not been studied in children with
      seasonal allergic rhinitis (SAR). The aim of this study was to evaluate the
      vitamin D levels of children with SAR and to compare them to levels in healthy
      children during pollen season. METHODS: This study was conducted in 100 children
      with SAR and 100 healthy controls. Clinical and laboratory evaluations and
      vitamin D analyses of all the participants were performed between the months of
      April and July. Pollen sensitization was detected in the patient group using a
      skin prick test. 25(OH)D3 levels were compared between the patient and control
      groups. Associations among the patient 25(OH)D3 levels and their demographic,
      clinical, and laboratory characteristics were analyzed. RESULTS: Overall, 72% of
      the patients were male, the median age was 12.35 years (range: 6-17.8 years), and
      the median body mass index value was 19.15 (range: 13.6-27.8). There were no
      differences between the patients and healthy controls in terms of gender, age, or
      body mass index. The mean levels of 25(OH)D3 (20.78+/-6) in patients were higher
      than those of the controls (17.92+/-4). In the patient group, no associations
      were found among 25(OH)D3 levels, demographic characteristics, atopy test
      results, atopy history, severity of rhinitis, and the total four symptoms score
      (all P>.05). CONCLUSIONS: During pollen season, children with SAR may have higher
      vitamin D levels than healthy controls. The presence of asthma and/or atopic
      dermatitis in addition to SAR did not change this result.

PMID- 28452069
TI  - The HDAC6 Inhibitor Tubacin Induces Release of CD133+ Extracellular Vesicles From
      Cancer Cells.
AB  - Tumor-derived extracellular vesicles (EVs) are emerging as an important mode of
      intercellular communication, capable of transferring biologically active
      molecules that facilitate the malignant growth and metastatic process. CD133
      (Prominin-1), a stem cell marker implicated in tumor initiation, differentiation
      and resistance to anti-cancer therapy, is reportedly associated with EVs in
      various types of cancer. However, little is known about the factors that regulate
      the release of these CD133+ EVs. Here, we report that the HDAC6 inhibitor tubacin
      promoted the extracellular release of CD133+ EVs from human FEMX-I metastatic
      melanoma and Caco-2 colorectal carcinoma cells, with a concomitant downregulation
      of intracellular CD133. This effect was specific for tubacin, as inhibition of
      HDAC6 deacetylase activity by another selective HDAC6 inhibitor, ACY-1215 or the
      pan-HDAC inhibitor trichostatin A (TSA), and knockdown of HDAC6 did not enhance
      the release of CD133+ EVs. The tubacin-induced EV release was associated with
      changes in cellular lipid composition, loss of clonogenic capacity and decrease
      in the ability to form multicellular aggregates. These findings indicate a novel
      potential anti-tumor mechanism for tubacin in CD133-expressing malignancies. J.
      Cell. Biochem. 118: 4414-4424, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28452070
TI  - Effect of exergames on musculoskeletal pain: A systematic review and meta
      analysis.
AB  - The main objective was to systematically review the scientific literature about
      the effects of exergame-based interventions on musculoskeletal pain, as well as
      to provide directions for the clinical practice. A systematic search was
      conducted in four electronic databases following PRISMA guidelines. The inclusion
      criteria were as follows: (a) the subjects were suffering musculoskeletal pain,
      (b) the study was randomized controlled trial (RCT), (c) intervention was based
      on exergames, (d) the article was written in English, and (e) the article was not
      an abstract or summary presented in a congress or conference. Risk of bias and
      quality of evidence were evaluated using the PEDro Scale and GRADE approach,
      respectively. A meta-analysis was carried out to determine effect sizes. Seven
      studies were selected in the systematic review. The meta-analysis included those
      six articles which reported means and SD before and after treatment and used a
      visual analog scale or a Numeric Pain Rating Scale. Four of the seven articles
      reported significant reduction in pain while the rest did not found any
      significant change in pain after the intervention. The overall effect size for
      pain was -0.51 (95% CI from -1.25 to 0.23) with large heterogeneity. Although
      four of the seven articles reported significant within-group differences, zero
      was included in the CI of the overall effect size. Therefore, up-to-date there is
      not enough evidence to conclude that exergames improve musculoskeletal pain.

PMID- 28452071
TI  - Oxidative stress in asthmatic and non-asthmatic adolescent swimmers-A breathomics
      approach.
AB  - : We hypothesize that oxidative stress induced by trichloramine exposure during
      swimming could be related to etiopathogenesis of asthma among elite swimmers.
      AIM: To investigate the effect of a swimming training session on oxidative stress
      markers of asthmatic compared to non-asthmatic elite swimmers using exhaled
      breath (EB) metabolomics. METHODS: Elite swimmers annually screened in our
      department (n=27) were invited and those who agreed to participate (n=20, of
      which 9 with asthma) had EB collected (Tedlar(r) bags) before and after a
      swimming training session. SPME fiber (DVB/CAR/PDMS) was used to extract EB
      metabolites followed by a multidimensional gas chromatography analysis (GC*GC
      ToFMS). Dataset comprises eight metabolites end products of lipid peroxidation:
      five aliphatic alkanes (nonane, 2,2,4,6,6-pentamethylheptane, decane, dodecane,
      and tetradecane) and three aldehydes (nonanal, decanal, and dodecanal). To assess
      exercise impact on lipid peroxidation markers, data were analyzed using principle
      component analysis (PCA), which was run on the original data set and on the data
      set constructed using differences in the metabolite total areas before and after
      exercise session. RESULTS: Heatmap representation revealed that metabolites
      content decreased after exercise, both for control and asthma groups; however,
      the greater decrease was observed for controls. Asthmatics and controls did not
      form separated clusters; however, control swimmers demonstrated a more varied
      response to the exercise being dispersed along all score plot. CONCLUSION: In
      well-trained athletes, swimming is associated with a decrease in oxidative stress
      markers independently of the presence of asthma, although a more pronounced
      decrease was seen in controls.

PMID- 28452072
TI  - PGC-1alpha in Melanoma: A Key Factor for Antioxidant Response and Mitochondrial
      Function.
AB  - Melanocortin 1 receptor (MC1R) and BRAF are common mutations in melanoma. Through
      different pathways, they each regulate the expression of PGC-1alpha, which is a
      key factor in the regulation of mitochondrial biogenesis and the antioxidant
      response. Our aim was to study the importance of the different regulatory
      characteristics of MC1R and BRAF on the pathways they regulate in melanoma. For
      this purpose, ROS production, levels of gene expression and enzymatic activities
      were analyzed in HBL and MeWo, with wild-type MC1R and BRAF, and A375 cells with
      mutant MC1R and BRAF. HBL cells showed a functional MC1R-PGC-1alpha pathway and
      exhibited the lowest ROS production, probably because of a better mitochondrial
      pool and the presence of UCP2. On the other hand, MeWo cells showed elevated
      levels of PGC-1alpha but also high ROS production, similar to the A375 cells,
      along with an activated antioxidant response and significantly low levels of
      UCP2. Finally, A375 cells are mutant for BRAF, and thus showed low levels of PGC
      1alpha. Consequently, A375 cells exhibited poor mitochondrial biogenesis and
      function, and no antioxidant response. These results show the importance of the
      activation of the MC1R-PGC-1alpha pathway for mitochondrial biogenesis and
      function in melanoma development, as well as BRAF for the antioxidant response
      regulated by PGC-1alpha. J. Cell. Biochem. 118: 4404-4413, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28452073
TI  - Analyzing the capacity of the Daphnia magna and Pseudokirchneriella subcapitata
      bioavailability models to predict chronic zinc toxicity at high pH and low
      calcium concentrations and formulation of a generalized bioavailability model for
      D. magna.
AB  - Risk assessment in the European Union implements Zn bioavailability models to
      derive predicted-no-effect concentrations for Zn. These models are validated
      within certain boundaries (i.e., pH <= 8 and Ca concentrations >= 5mg/L), but a
      substantial fraction of the European surface waters falls outside these
      boundaries. Therefore, we evaluated whether the chronic Zn biotic ligand model
      (BLM) for Daphnia magna and the chronic bioavailability model for
      Pseudokirchneriella subcapitata could be extrapolated to pH > 8 and Ca
      concentrations < 5 mg/L. Results from D. magna experiments suggested that the BLM
      is not able to reflect the pH effect over a broad pH range (5.5-8.5). In
      addition, because of Ca deficiency of D. magna in the soft water tests, we cannot
      conclude whether the BLM is applicable below its Ca boundary. Results for P.
      subcapitata experiments showed that the bioavailability model can accurately
      predict Zn toxicity for Ca concentrations down to 0.8 mg/L and pH values up to
      8.5. Because the chronic Zn BLM for D. magna could not be extrapolated beyond its
      validity boundaries for pH, a generalized bioavailability model (gBAM) was
      developed. Of 4 gBAMs developed, we recommend the use of gBAM-D, which combines a
      log-linear relation between the 21-d median effective concentrations (expressed
      as free Zn2+ ion activity) and pH, with more conventional BLM-type competition
      constants for Na, Ca, and Mg. This model is a first step in further improving the
      accuracy of chronic toxicity predictions of Zn as a function of water chemistry,
      which can decrease the uncertainty in implementing the bioavailability-based
      predicted-no-effect concentration in the risk assessment of high-pH and low-Ca
      concentration regions in Europe. Environ Toxicol Chem 2017;36:2781-2798. (c) 2017
      SETAC.

PMID- 28452074
TI  - Clinicopathologic features and immunohistochemical spectrum of 11 cases of
      epithelioid malignant peripheral nerve sheath tumors, including INI1/SMARCB1
      results and BRAF V600E analysis.
AB  - Epithelioid malignant peripheral nerve sheath tumor (MPNST) is a rare, relatively
      less chemosensitive sarcoma. We report clinicopathologic features of 11
      epithelioid MPNSTs, including rare forms, along with INI1 immunostaining and BRAF
      V600E mutation results. BRAF V600E mutation was tested by Real-time polymerase
      chain reaction (PCR) technique. Eleven tumors occurred in six men and five women
      (M:F ratio = 0.85:1) within an age range of 5-73 years (average = 44), mostly in
      lower limbs (five), followed by upper limbs (four). Tumor size (n = 6), varied
      from 3.1 to 15 cm (average = 8.3). Histopathologically, most tumors were
      multilobular, characterized by epithelioid to round-shaped, malignant cells,
      along with spindle cells (three cases), "rhabdoid-like" cells (seven cases) and
      pleomorphic giant cells (single case). By immunohistochemistry, tumor cells were
      positive for S100 protein (11/11) (100%), EMA (3/7) (42.8%), pan CK(2/7) (28.5%),
      and HMB45 (1/11) (9%), while these were negative for Melan A (0/11) and INI1
      (3/11), including a single tumor, displaying HMB45 positivity. BRAF V600E
      mutation was positive in 1/8 cases, that lacked melanocytic marker expression.
      All patients (n = 5) were treated by surgical resection. During follow-up (n = 8,
      median duration = 23 months), four patients developed tumor recurrences and four
      developed metastasis, mostly to lymph nodes (3). Finally, four patients were
      alive with disease, two were alive with no evidence of disease, and two patients
      died of disease. Epithelioid MPNSTs have a diverse histopathologic spectrum. Loss
      of INI1 is useful, including in identifying rare forms of epithelioid MPNST,
      displaying melanocytic differentiation. Most tumors are treated by surgical
      resection. Loss of INI1 and the presence of BRAF V600E mutation in some cases
      raises future possibility of exploring targeted therapy in those, rare
      epithelioid MPNSTs.

PMID- 28452075
TI  - Relation of infant dietary patterns to allergic outcomes in early childhood.

PMID- 28452076
TI  - Comparison between universal adhesives and two-step self-etch adhesives in terms
      of dentin bond fatigue durability in self-etch mode.
AB  - This aim of this study was to compare universal adhesives and two-step self-etch
      adhesives in terms of dentin bond fatigue durability in self-etch mode. Three
      universal adhesives - Clearfil Universal, G-Premio Bond, and Scotchbond Universal
      Adhesive - and three-two-step self-etch adhesives - Clearfil SE Bond, Clearfil SE
      Bond 2, and OptiBond XTR - were used. The initial shear bond strength and shear
      fatigue strength of resin composite bonded to adhesive on dentin in self-etch
      mode were determined. Scanning electron microscopy observations of fracture
      surfaces after bond strength tests were also made. The initial shear bond
      strength of universal adhesives was material dependent, unlike that of two-step
      self-etch adhesives. The shear fatigue strength of Scotchbond Universal Adhesive
      was not significantly different from that of two-step self-etch adhesives, unlike
      the other universal adhesives. The shear fatigue strength of universal adhesives
      differed depending on the type of adhesive, unlike those of two-step self-etch
      adhesives. The results of this study encourage the continued use of two-step self
      etch adhesive over some universal adhesives but suggest that changes to the
      composition of universal adhesives may lead to a dentin bond fatigue durability
      similar to that of two-step self-etch adhesives.

PMID- 28452078
TI  - Daily oscillation of odorant detection in rat olfactory epithelium.
AB  - Most of biological variables follow a daily rhythm. It holds true as well for
      sensory capacities as two decades of research have demonstrated that the odorant
      induced activity in the olfactory bulbs oscillates during the day. Olfactory
      bulbs are the first central nervous system structures, which receive inputs from
      the olfactory neurons located in the nose olfactory epithelium in vertebrates. So
      far, data on variation in odorant detection in the olfactory epithelium
      throughout the day are missing. Using electroolfactogram recordings in rats
      housed under daily light and dark cycles, we found that the olfactory epithelium
      responsiveness varies during the day with a maximum in the beginning of the light
      phase. This fluctuation was consistent with cycling of transduction pathway gene
      expression in the olfactory epithelium examined by qPCR. It was also consistent
      with the levels of two transduction pathway proteins (olfactory-type G protein
      and adenylyl cyclase III) examined by western blot. Daily variations were also
      observed at the level of olfactory sensory neurons responses recorded by patch
      clamp. To rule out a potential effect of the feeding status of the animal, we
      examined the variation in odorant response in starved animals during the day. We
      observed a similar pattern to ad libidum fed animals. Taken together, our results
      reveal that the olfactory epithelium sensitivity varies during the day in part
      due to modulation of the very first step of odorant detection.

PMID- 28452077
TI  - Structure and function of human muscle fibres and muscle proteome in physically
      active older men.
AB  - KEY POINTS: Loss of muscle mass and strength in the growing population of elderly
      people is a major health concern for modern societies. This condition, termed
      sarcopenia, is a major cause of falls and of the subsequent increase in morbidity
      and mortality. Despite numerous studies on the impact of ageing on individual
      muscle fibres, the contribution of single muscle fibre adaptations to ageing
      induced atrophy and functional impairment is still unsettled. The level of
      physical function and disuse is often associated with ageing. We studied
      relatively healthy older adults in order to understand the effects of ageing per
      se without the confounding impact of impaired physical function. We found that in
      healthy ageing, structural and functional alterations of muscle fibres occur.
      Protein post-translational modifications, oxidation and phosphorylation
      contribute to such alterations more than loss of myosin and other muscle protein
      content. ABSTRACT: Contradictory results have been reported on the impact of
      ageing on structure and functions of skeletal muscle fibres, likely to be due to
      a complex interplay between ageing and other phenomena such as disuse and
      diseases. Here we recruited healthy, physically and socially active young (YO)
      and elderly (EL) men in order to study ageing per se without the confounding
      effects of impaired physical function. In vivo analyses of quadriceps and in
      vitro analyses of vastus lateralis muscle biopsies were performed. In EL
      subjects, our results show that (i) quadriceps volume, maximum voluntary
      contraction isometric torque and patellar tendon force were significantly lower;
      (ii) muscle fibres went through significant atrophy and impairment of specific
      force (isometric force/cross-sectional area) and unloaded shortening velocity;
      (iii) myosin/actin ratio and myosin content in individual muscle fibres were not
      altered; (iv) the muscle proteome went through quantitative adaptations, namely
      an up-regulation of the content of several groups of proteins among which were
      myofibrillar proteins and antioxidant defence systems; (v) the muscle proteome
      went through qualitative adaptations, namely phosphorylation of several proteins,
      including myosin light chain-2 slow and troponin T and carbonylation of myosin
      heavy chains. The present results indicate that impairment of individual muscle
      fibre structure and function is a major feature of ageing per se and that
      qualitative adaptations of muscle proteome are likely to be more involved than
      quantitative adaptations in determining such a phenomenon.

PMID- 28452079
TI  - Frequency-dependent selection acting on the widely fluctuating sex ratio of the
      aphid Prociphilus oriens.
AB  - Frequency-dependent selection is a fundamental principle of adaptive sex ratio
      evolution in all sex ratio theories but has rarely been detected in the wild.
      Through long-term censuses, we confirmed large fluctuations in the population sex
      ratio of the aphid Prociphilus oriens and detected frequency-dependent selection
      acting on these fluctuations. Fluctuations in the population sex ratio were
      partly attributable to climatic factors during the growing season. Climatic
      factors likely affected the growth conditions of host plants, which in turn led
      to yearly fluctuations in maternal conditions and sex ratios. In the process of
      frequency-dependent selection, female proportion higher or lower than ca. 60% was
      associated with a reduction or increase in female proportion, respectively, the
      next year. The rearing of aphid clones in the laboratory indicated that mothers
      of each clone produced an increasing number of females as maternal size
      increased. However, the mean male number was not related to maternal size, but
      varied largely among clones. Given genetic variance in the ability to produce
      males among clones, selection should favour clones that can produce more numerous
      males in years with a high female proportion. Population-level sex allocation to
      females was on average 71%-73% for three localities and more female-biased when
      maternal conditions were better. This tendency was accounted for by the
      hypothesis of competition among foundresses rather than the hypothesis of local
      mate competition. We conclude that despite consistent operation of frequency
      dependent selection, the sex ratio continues to fluctuate because environmental
      conditions always push it away from equilibrium.

PMID- 28452082
TI  - Reproductive tract modifications of the boar sperm surface.
AB  - The sperm cell has a unique, polarized, and segregated surface that is modified
      extensively by the changing environments in both the male and the female
      reproductive tracts. The sperm cannot refresh its surface, as protein translation
      and membrane recycling by intracellular vesicular transport have ceased upon its
      maturation. So, how is the sperm surface modified in the reproductive tracts and
      how do these processes affect fertilization? This review traces these
      modifications as boar sperm travels from their liberation from the Sertoli cell
      into the lumen of seminiferous tubules of the testis to the site of fertilization
      in the ampulla of the oviduct in the sow, via an artificial insemination route.
      The effect of sperm dilution for artificial insemination, as well as more
      extensive sperm processing for in vitro fertilization, cryopreservation, or sex
      sorting, are also discussed with respect to how these procedures affect sperm
      surface organization and fertilization capacity.

PMID- 28452080
TI  - Autism: a transdiagnostic, dimensional, construct of reasoning?
AB  - The concept of autism has changed across time, from the Bleulerian concept, which
      defined it as one of several symptoms of dementia praecox, to the present-day
      concept representing a pervasive development disorder. The present theoretical
      contribution to this special issue of EJN on autism introduces new theoretical
      ideas and discusses them in light of selected prior theories, clinical examples,
      and recent empirical evidence. The overall aim is to identify some present
      challenges of diagnostic practice and autism research and to suggest new pathways
      that may help direct future research. Future research must agree on the
      definitions of core concepts such as autism and psychosis. A possible
      redefinition of the concept of autism may be a condition in which the rationale
      of an individual's behaviour differs qualitatively from that of the social
      environment due to characteristic cognitive impairments affecting reasoning. A
      broad concept of psychosis could focus on deviances in the experience of reality
      resulting from impairments of reasoning. In this light and consistent with recent
      empirical evidence, it may be appropriate to redefine dementia praecox as a
      developmental disorder of reasoning. A future challenge of autism research may be
      to develop theoretical models that can account for the impact of complex
      processes acting at the social level in addition to complex neurobiological and
      psychological processes. Such models could profit from a distinction among
      processes related to (i) basic susceptibility, (ii) adaptive processes and (iii)
      decompensating factors involved in the development of manifest illness.

PMID- 28452081
TI  - Heightened brain response to pain anticipation in high-functioning adults with
      autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is marked by both socio-communicative difficulties
      and abnormalities in sensory processing. Much of the work on sensory deficits in
      ASD has focused on tactile sensations and the perceptual aspects of
      somatosensation, such as encoding of stimulus intensity and location. Although
      aberrant pain processing has often been noted in clinical observations of
      patients with ASD, it remains largely uninvestigated. Importantly, the neural
      mechanism underlying higher order cognitive aspects of pain processing such as
      pain anticipation also remains unknown. Here we examined both pain perception and
      anticipation in high-functioning adults with ASD and matched healthy controls
      (HC) using an anticipatory pain paradigm in combination with functional magnetic
      resonance imaging (fMRI) and concurrent skin conductance response (SCR)
      recording. Participants were asked to choose a level of electrical stimulation
      that would feel moderately painful to them. Compared to HC group, ASD group chose
      a lower level of stimulation prior to fMRI. However, ASD participants showed
      greater activation in both rostral and dorsal anterior cingulate cortex during
      the anticipation of stimulation, but not during stimulation delivery. There was
      no significant group difference in insular activation during either pain
      anticipation or perception. However, activity in the left anterior insula
      correlated with SCR during pain anticipation. Taken together, these results
      suggest that ASD is marked with aberrantly higher level of sensitivity to
      upcoming aversive stimuli, which may reflect abnormal attentional orientation to
      nociceptive signals and a failure in interoceptive inference.

PMID- 28452083
TI  - Neurobiological bases of autism-epilepsy comorbidity: a focus on
      excitation/inhibition imbalance.
AB  - Autism spectrum disorders (ASD) and epilepsy are common neurological diseases of
      childhood, with an estimated incidence of approximately 0.5-1% of the worldwide
      population. Several genetic, neuroimaging and neuropathological studies clearly
      showed that both ASD and epilepsy have developmental origins and a substantial
      degree of heritability. Most importantly, ASD and epilepsy frequently coexist in
      the same individual, suggesting a common neurodevelopmental basis for these
      disorders. Genome-wide association studies recently allowed for the
      identification of a substantial number of genes involved in ASD and epilepsy,
      some of which are mutated in syndromes presenting both ASD and epilepsy clinical
      features. At the cellular level, both preclinical and clinical studies indicate
      that the different genetic causes of ASD and epilepsy may converge to perturb the
      excitation/inhibition (E/I) balance, due to the dysfunction of excitatory and
      inhibitory circuits in various brain regions. Metabolic and immune dysfunctions,
      as well as environmental causes also contribute to ASD pathogenesis. Thus, an E/I
      imbalance resulting from neurodevelopmental deficits of multiple origins might
      represent a common pathogenic mechanism for both diseases. Here, we will review
      the most significant studies supporting these hypotheses. A deeper understanding
      of the molecular and cellular determinants of autism-epilepsy comorbidity will
      pave the way to the development of novel therapeutic strategies.

PMID- 28452084
TI  - Annual hospitalization rates for children with asthma are inversely associated
      with total hours of sunshine in English regions.

PMID- 28452086
TI  - Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis
      of the APOSTEL-III trial.
AB  - OBJECTIVE: Brain injury in neonates born prematurely is associated strongly with
      poor neurodevelopmental outcome. The aim of this study was to evaluate whether
      tocolysis with nifedipine or atosiban in women with threatened preterm birth can
      reduce the incidence of overall brain injury in neonates born prematurely.
      METHODS: This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical
      Trial Registry, no. NTR2947), a randomized clinical trial in which women with
      threatened preterm labor between 25 and 34 weeks of gestation were allocated to
      treatment with nifedipine or atosiban. In this secondary analysis, women
      delivered at <= 32 weeks of gestational age in the two main contributing centers
      were included. Primary outcome was the presence of neonatal brain injury, which
      was defined as presence of abnormalities on ultrasound investigation and
      classified into mild and severe. To evaluate type and severity of brain injury,
      all neonatal ultrasounds performed during neonatal intensive and medium care
      admission were analyzed. To test the robustness of our results, a sensitivity
      analysis was performed assessing differences in baseline or known risk factors
      for brain injury. RESULTS: A total of 117 neonates (from 102 women) were studied,
      of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was
      observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%)
      in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain
      injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups
      (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between
      the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in
      the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (>=
      Grade I) was the most frequently seen ultrasound abnormality, observed in 18
      (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR,
      0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal
      age and gestational age at randomization, showed no statistical difference
      between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27).
      CONCLUSION: In children born before 32 weeks of gestation after the use of
      tocolytics, the prevalence of brain injury was high. No significant differences
      were found with respect to overall brain injury between neonates exposed to
      nifedipine and those exposed to atosiban. However, as this study was a secondary
      analysis of the APOSTEL III trial, it was underpowered for brain injury.
      Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28452085
TI  - Use of chimeric type IV secretion systems to define contributions of outer
      membrane subassemblies for contact-dependent translocation.
AB  - Recent studies have shown that conjugation systems of Gram-negative bacteria are
      composed of distinct inner and outer membrane core complexes (IMCs and OMCCs,
      respectively). Here, we characterized the OMCC by focusing first on a cap domain
      that forms a channel across the outer membrane. Strikingly, the OMCC caps of the
      Escherichia coli pKM101 Tra and Agrobacterium tumefaciens VirB/VirD4 systems are
      completely dispensable for substrate transfer, but required for formation of
      conjugative pili. The pKM101 OMCC cap and extended pilus also are dispensable for
      activation of a Pseudomonas aeruginosa type VI secretion system (T6SS). Chimeric
      conjugation systems composed of the IMCpKM101 joined to OMCCs from the A.
      tumefaciens VirB/VirD4, E. coli R388 Trw, and Bordetella pertussis Ptl systems
      support conjugative DNA transfer in E. coli and trigger P. aeruginosa T6SS
      killing, but not pilus production. The A. tumefaciens VirB/VirD4 OMCC, solved by
      transmission electron microscopy, adopts a cage structure similar to the pKM101
      OMCC. The findings establish that OMCCs are highly structurally and functionally
      conserved - but also intrinsically conformationally flexible - scaffolds for
      translocation channels. Furthermore, the OMCC cap and a pilus tip protein
      coregulate pilus extension but are not required for channel assembly or function.

PMID- 28452087
TI  - Cytotoxic CD8+ T cell ablation enhances the capacity of regulatory T cells to
      delay viral elimination in Theiler's murine encephalomyelitis.
AB  - Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a
      commonly used infectious animal model for multiple sclerosis. The study aim was
      to test the hypothesis whether cytotoxic T cell responses account for the limited
      impact of regulatory T cells on antiviral immunity in TME virus-induced
      demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected
      C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody
      complexes to expand regulatory T cells ("Treg-expansion"), (ii) anti-CD8
      antibodies to deplete cytotoxic T cells ("CD8-depletion") or (iii) with a
      combination of Treg-expansion and CD8-depletion ("combined treatment") prior to
      infection. Results showed that "combined treatment", but neither sole "Treg
      expansion" nor "CD8-depletion," leads to sustained hippocampal infection and
      virus spread to the spinal cord in C57BL/6 mice. Prolonged infection reduces
      myelin basic protein expression in the spinal cord together with increased
      accumulation of beta-amyloid precursor protein in axons, characteristic of myelin
      loss and axonal damage, respectively. Chronic spinal cord infection upon
      "combined treatment" was also associated with increased T and B cell recruitment,
      accumulation of CD107b+ microglia/macrophages and enhanced mRNA expression of
      interleukin (IL)-1alpha, IL-10 and tumor necrosis factor alpha. In conclusion,
      data revealed that the suppressive capacity of Treg on viral elimination is
      efficiently boosted by CD8-depletion, which renders C57BL/6 mice susceptible to
      develop chronic neuroinfection and TMEV-IDD.

PMID- 28452089
TI  - Congruent population structure across paralogous and nonparalogous loci in Salish
      Sea chum salmon (Oncorhynchus keta).
AB  - Whole-genome duplications are major evolutionary events with a lasting impact on
      genome structure. Duplication events complicate genetic analyses as paralogous
      sequences are difficult to distinguish; consequently, paralogs are often excluded
      from studies. The effects of an ancient whole-genome duplication (approximately
      88 MYA) are still evident in salmonids through the persistence of numerous
      paralogous gene sequences and partial tetrasomic inheritance. We use restriction
      site-associated DNA sequencing on 10 collections of chum salmon from the Salish
      Sea in the USA and Canada to investigate genetic diversity and population
      structure in both tetrasomic and rediploidized regions of the genome. We use a
      pedigree and high-density linkage map to identify paralogous loci and to
      investigate genetic variation across the genome. By applying multivariate
      statistical methods, we show that it is possible to characterize paralogous loci
      and that they display similar patterns of population structure as the diploidized
      portion of the genome. We find genetic associations with the adaptively important
      trait of run-timing in both sets of loci. By including paralogous loci in genome
      scans, we can observe evolutionary signals in genomic regions that have routinely
      been excluded from population genetic studies in other polyploid-derived species.

PMID- 28452088
TI  - Myosin II activity is required for structural plasticity at the axon initial
      segment.
AB  - In neurons, axons possess a molecularly defined and highly organised proximal
      region - the axon initial segment (AIS) - that is a key regulator of both
      electrical excitability and cellular polarity. Despite existing as a large, dense
      structure with specialised cytoskeletal architecture, the AIS is surprisingly
      plastic, with sustained alterations in neuronal activity bringing about
      significant alterations to its position, length or molecular composition.
      However, although the upstream activity-dependent signalling pathways that lead
      to such plasticity have begun to be elucidated, the downstream mechanisms that
      produce structural changes at the AIS are completely unknown. Here, we use
      dissociated cultures of rat hippocampus to show that two forms of AIS plasticity
      in dentate granule cells - long-term relocation, and more rapid shortening - are
      completely blocked by treatment with blebbistatin, a potent and selective myosin
      II ATPase inhibitor. These data establish a link between myosin II and AIS
      function, and suggest that myosin II's primary role at the structure may be to
      effect activity-dependent morphological alterations.

PMID- 28452090
TI  - Push-Pull-Type Polychlorotriphenylmethyl Radicals: New Two-Photon Absorbers and
      Dyes for Generation of Photo-Charges.
AB  - Tri(4-iodo-2,3,5,6-tetrachlorophenyl)methane (2) is reported as a general
      building block for the synthesis of various pi-conjugated
      polychlorotriphenylmethyl (PTM) radicals. Three push-pull-type triphenylamine
      substituted PTM radicals with different substitution patterns were prepared and
      all exhibited intense inter-valence charge-transfer bands and large two-photon
      absorption (TPA) cross sections. Moreover, increase of solvent polarity also
      resulted in improved TPA response. The charge-transfer character of the relevant
      excited states provoked the efficient photo-generation of charges, anions in the
      PTM and cations in the amine arms, driven by the amphoteric redox character and
      the small coupling between donor and acceptor.

PMID- 28452091
TI  - An Aminocatalyzed Stereoselective Strategy for the Formal alpha-Propargylation of
      Ketones.
AB  - A two-step reaction sequence is described for the asymmetric formal alpha
      propargylation of ketones. This approach takes advantage of an aminocatalyzed
      conjugate addition of ketones to alkylidene isoxazol-5-ones, followed by a
      controlled nitrosative degradation event. The target compounds can be accessed in
      broad scope, in moderate to good yields, perfect diastereocontrol and good to
      excellent enantioselectivity.

PMID- 28452092
TI  - Prospective assessment of INTERGROWTH-21st and World Health Organization
      estimated fetal weight reference curves.
AB  - OBJECTIVES: To assess the suitability of the new INTERGROWTH-21st and World
      Health Organization (WHO) estimated fetal weight (EFW) references in a Southern
      Chinese population. A secondary aim was to determine the accuracy of EFW by
      assessing the difference between EFW and actual birth weight. METHODS: This was a
      prospective cross-sectional cohort study. Viable singleton pregnancies at 11-13
      weeks' gestation were recruited to undergo a single standardized fetal biometric
      scan after 20 weeks. The gestational age at which the scan was performed was
      allocated randomly at the time of recruitment. EFW was predicted using both the
      Hadlock and INTERGROWTH-21st weight estimation model formulae. Population
      specific EFW references were constructed. Z-scores were used to compare these
      references against the INTERGROWTH-21st and WHO international size references.
      Gestational-age-adjusted projection was used to assess the difference between EFW
      on the day of delivery and birth weight for fetuses having biometry scans >= 34
      weeks. RESULTS: Fetuses of 970 participants had biometry scans. The median number
      of scans per gestational week was 48 (interquartile range, 43-53). Z-score
      comparison indicated that the WHO 10th , 50th and 90th centiles of the EFW
      reference were consistently higher than the corresponding local centiles, whilst
      the INTERGROWTH-21st 10th centile was lower. Fewer than 2% of fetuses scanned at
      or after 34 weeks would be considered as potentially large-for-gestational age,
      irrespective of which model was used to predict weight. Adopting the WHO
      international reference would result in approximately one in six fetuses being
      regarded as potentially small-for-gestational age, 50% more than the number
      determined using a population-specific reference. Systematic errors of
      extrapolated EFW were similar, ranging from 5.5% to 7.4%. CONCLUSIONS: Centers
      seeking to use new references, such as the INTERGROWTH-21st and/or WHO
      international references, as a means of determining whether a fetus is small- or
      large-for-gestational age, would be advised to assess the suitability of these
      references within their own population using standardized methodology. Copyright
      (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28452093
TI  - Effects of Helicobacter pylori treatment on rosacea: A single-arm clinical trial
      study.
AB  - Rosacea is a chronic dermatological disease. Helicobacter pylori has been
      discussed as one of its causative factors. In this clinical trial study, we
      attempted to evaluate the effect of H. pylori standard eradication protocol on
      the rosacea clinical course. In this single-arm clinical trial, patients
      ascertained to have H. pylori infection based on serological studies were
      assessed to examine existence of rosacea. Patients with concurrent rosacea and H.
      pylori infection were included in the study and underwent standard H. pylori
      eradication therapy. Rosacea was evaluated using the Duluth rosacea grading score
      at the beginning, 2 months later and at the end of the trial (day 180). Of 872
      patients positive for H. pylori, 167 patients (19.15%) manifested the clinical
      features of rosacea. The patients with concurrent rosacea were younger (P <
      0.001) and with a female sex predominance (P = 0.03) when compared with rosacea
      free patients. Of 167 patients, 150 received H. pylori eradication therapy,
      demonstrating a 92% (138/150) cure rate. The rosacea Duluth score grading on day
      0, 60 and 180 among 138 patients significantly decreased in most of the criteria
      except for telangiectasias (P = 0.712), phymatous changes (P = 0.535) and the
      existence of peripheral involvement (P = 0.431). The present study concluded that
      H. pylori eradication leads to improvement of rosacea.

PMID- 28452094
TI  - Imaging characteristics of liver Langerhans cell histiocytosis in children.
AB  - BACKGROUND: Hepatic involvement of Langerhans cell histiocytosis (LCH) in
      children is important not only for prognostic purposes, but also as a guide for
      therapeutic strategies. The purpose of this study was to evaluate the imaging
      characteristics of hepatic LCH by computed tomography (CT) and magnetic resonance
      imaging (MRI) in children. METHODS: Imaging features of 17 children with hepatic
      LCH diagnosed by physical examination, laboratory and histopathological tests
      were analyzed retrospectively. The mean patient age was 3.6 +/- 2.3 years (range,
      9 months - 10 years). The mean disease duration was 6.7 +/- 8.3 months (range, 5
      days - 4 years). 11 patients underwent hepatic CT scans, and 6 patients underwent
      MRI scans. RESULTS: The imaging manifestations observed were hepatomegaly (16/17)
      and diffuse hypodense nodules ranging in size from 0.5 - 1.7 cm in diameter. The
      nodules were hypodense on plain CT and showed mild to moderate ring enhancement
      on contrast-enhanced CT. MRI showed slightly high signal intensity on T1-weighted
      images and high signal intensity on T2-weighted images with clear boundaries and
      mild ring enhancement. Contrast-enhanced CT showed periportal hypodensity
      ("periportal halo sign"), mild irregular intrahepatic bile duct dilatation, liver
      cirrhosis, and lymphadenopathy of the hilar or retroperitoneal region.
      CONCLUSIONS: CT and MRI imaging characteristics suggestive of liver involvement
      in patients with LCH may be helpful in evaluating the prognosis and management of
      LCH. Small hypodense nodules on CT or mild signal intensity nodules on MRI may
      suggest a better prognosis for liver LCH in children. This article is protected
      by copyright. All rights reserved.

PMID- 28452095
TI  - Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy
      to oral antidiabetic agents in patients with type 2 diabetes in China.
AB  - AIMS: To estimate the long-term cost-effectiveness of exenatide twice daily vs
      insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs)
      for Chinese patients with type 2 diabetes (T2DM). METHODS: The Cardiff Diabetes
      Model was used to simulate disease progression and estimate the long-term effects
      of exenatide twice daily vs insulin glargine once daily. Patient profiles and
      treatment effects required for the model were obtained from literature reviews
      (English and Chinese databases) and from a meta-analysis of 8 randomized
      controlled trials comparing exenatide twice daily with insulin glargine once
      daily add-on to OADs for T2DM in China. Medical expenditure data were collected
      from 639 patients with T2DM (aged >=18 years) with and without complications
      incurred between January 1, 2014 and December 31, 2015 from claims databases in
      Shandong, China. Costs (2014 Chinese Yuan [Y]) and benefits were estimated, from
      the payers' perspective, over 40 years at a discount rate of 3%. A series of
      sensitivity analyses were performed. RESULTS: Patients on exenatide twice daily +
      OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic
      events and lower total costs compared with those on insulin glargine once daily +
      OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost
      saving of Y117 706 gained was associated with exenatide twice daily vs insulin
      glargine once daily. (i.e. cost saving of Y60 764/QALY) per patient. CONCLUSIONS:
      In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice
      daily is a cost-effective add-on therapy alternative to insulin glargine once
      daily, and may address the problem of an excess of medical needs resulting from
      weight gain and hypoglycaemia in T2DM treatment.

PMID- 28452096
TI  - Kidney transplant after hematopoietic cell transplant in pediatrics: Infectious
      and immunosuppressive considerations.
AB  - Pediatric patients requiring kidney transplant after hematopoietic cell
      transplant receive multiple courses of immunosuppression placing them at risk for
      infection. To elucidate potential risk factors for infection, we compared the
      immunosuppressive regimens and infectious complications of pediatric kidney
      transplant recipients at a single institution who had previously undergone
      hematopoietic cell transplant from different donors to similar patients reported
      in the literature. Among the initial four post-hematopoietic cell transplant
      kidney transplant patients reviewed, viremia episodes were universal, including
      BK virus, Epstein-Barr virus, and human herpesvirus-6, with one death from
      presumed BK virus encephalitis. No viremia was reported in five similar cases in
      the literature. Risk factors for increased infection include use of
      lymphodepleting serotherapy in HCT conditioning, multiple HCTs, limited immune
      reconstitution time between transplants, increased pre-KTx viral burden, and use
      of T-cell-depleting versus -suppressive induction immunosuppression for KTx.
      These findings suggest that pediatric post-HCT KTx recipients are at increased
      risk for viral infections, likely benefitting from thorough pre-KTx evaluation of
      immune reconstitution and preferential use of non-T-cell-depleting induction
      therapy for KTx. We applied these recommendations to one subsequent post-HCT
      patient requiring KTx at our institution with excellent outcomes one year post
      KTx.

PMID- 28452097
TI  - Neutrophil gelatinase-associated lipocalin accurately predicts renal tubular
      injury in patients with chronic hepatitis B treated with nucleos(t)ide analogs.
AB  - AIM: Little is known about the impact of long-term use of nucleos(t)ide analogs
      on tubular function in patients with chronic hepatitis B. Previous studies showed
      that neutrophil gelatinase-associated lipocalin (NGAL) elevation was associated
      with renal tubular injury. We evaluated renal function markers and bone mineral
      density in patients treated long-term with adefovir dipivoxil (ADV) or entecavir
      (ETV). METHODS: In this cross-sectional study, we enrolled 78 patients (ADV, 36;
      ETV: 42), and 21 patients matched for age, observation time, and baseline
      estimated glomerular filtration rate from each group. RESULTS: Patients treated
      with ADV showed a significant increase in serum creatinine and urine beta2 
      microglobulin, and decreased estimated glomerular filtration rate and bone
      mineral density. Furthermore, the median levels of NGAL in patients treated with
      ADV were significantly higher than those of ETV (12.5 ng/mL vs. 2.5 ng/mL, P =
      0.020). The proportions of patients with proteinuria and phosphate <1 mmol/L in
      the ADV group were higher than those in the ETV group. Additionally, age, beta2 
      microglobulin, phosphate, and ADV use were associated with altered NGAL levels on
      multivariate analysis. Among the commonly used biomarkers, NGAL was the most
      useful (odds ratio = 5.72; P = 0.005) and specific (92% specificity at 18.1 ng/mL
      cut-off) in predicting low bone mass. CONCLUSIONS: Patients with chronic
      hepatitis B treated long-term with ADV showed elevated urinary NGAL levels.
      Neutrophil gelatinase-associated lipocalin was more specific in predicting low
      bone mass during therapy compared with beta2 -microglobulin, phosphate, and
      creatinine. In general, this analysis examined the value of NGAL as a renal
      tubular injury indicator, resulting from ADV use.

PMID- 28452098
TI  - Impact of bradycardia or asystole on neonatal cardiopulmonary resuscitation at
      birth.
AB  - BACKGROUND: Fetal hypoxia from intrapartum events can lead to absent heart rate
      (HR) or bradycardia at birth requiring aggressive neonatal resuscitation.
      Neonatal resuscitation guidelines do not differentiate bradycardia (HR <100
      beats/min) from absent HR at birth. Given that HR is the primary determinant of
      resuscitation, we hypothesize that infants with no HR at 1 min would require more
      extensive resuscitation with worse clinical outcome than infants with bradycardia
      at 1 min. METHODS: A retrospective analysis was performed in infants born between
      1 January 2000 and 31 December 2015 with no HR at 1 min (defined as Apgar score
      [AS] = 0 at 1 min; absent HR [AHR] group) or bradycardia at 1 min (AS = 1 at 1
      min). Patient demographics, resuscitation characteristics and clinical outcomes
      were analyzed in both the groups. RESULTS: Apgar score was significantly lower in
      the AHR group over time. The AHR group had significantly higher rates of
      intubation, chest compression (CC) and i.v. epinephrine (i.v. epi); resulting in
      longer duration of CC, time to HR > 100 beats/min and duration of resuscitation.
      Systematic hypotension and death were higher in the AHR group. On logistic
      regression, CC and cord pH were significantly correlated with AS = 0 at 1 min.
      Gestational age, birthweight, AS at 5 min, cord pH and first blood gas pH after
      resuscitation were related to overall mortality. CONCLUSIONS: Infants with AHR at
      1 min did worse than infants with bradycardia. Education focused on effective
      positive pressure ventilation and early use of i.v. epinephrine is essential for
      successful resuscitation of the depressed newborn.

PMID- 28452099
TI  - Poor sleep quality has an adverse effect on childhood asthma control and lung
      function measures.
AB  - BACKGROUND: It is unclear as to whether sleep respiratory breathing disorder
      (SRBD) is a risk factor for uncontrolled asthma in children. The aim of this
      study was therefore to investigate whether SRBD may have an adverse effect on
      childhood asthma control and lung function measures. METHODS: This was a cross
      sectional study of 220 children with well-controlled (n = 108), partly controlled
      (n = 92), and uncontrolled asthma (n = 20) according to the Global Initiative for
      Asthma guideline. SRBD was assessed using the Pediatric Sleep Questionnaire
      (PSQ). The association of SRBD with partly controlled/uncontrolled asthma was
      investigated on multivariate logistic regression analysis. RESULTS: Of 220
      children with asthma, 43 (19.6%) had SRBD: well-controlled, 16.7% (18/108);
      partly controlled, 21.7% (20/92); and uncontrolled, 25.0% (5/20; P = 0.54). There
      was a significant difference in forced expiratory volume in 1 s/forced vital
      capacity (FEV1 /FVC; P = 0.007) and childhood asthma control test (C-ACT) score
      (P < 0.001) according to asthma control status, but not in PSQ score (P = 0.18).
      Children with obstructive sleep apnea (PSQ >0.33) had a lower C-ACT score
      compared with controls (PSQ <=0.33; 19.6 +/- 5.1 vs 22.0 +/- 4.2, P = 0.002). PSQ
      score was negatively correlated with FEV1 /FVC (r = -0.16, P = 0.02). On
      multivariate logistic regression analysis, high PSQ score increased the odds of
      having partly controlled/uncontrolled asthma by 9.12 (95% CI: 1.04-79.72, P =
      0.046) after adjusting for confounding factors. CONCLUSION: SRBD is an
      independent risk factor for partly controlled/uncontrolled asthma and has an
      adverse effect on lung function measures in children. Further research is
      warranted to determine whether the improvement of sleep quality may also enhance
      level of asthma control and lung function in children.

PMID- 28452100
TI  - Pediatric psoriasis: Should we be concerned with comorbidity? Cross-sectional
      study.
AB  - BACKGROUND: Similarly to psoriasis in adults, recent research has linked
      psoriasis to several comorbidities in children. The aim of this study was
      therefore to describe comorbidities associated with pediatric psoriasis, to
      investigate their relationship with psoriasis characteristics and severity, and
      to perform a review of the literature. METHODS: A cross-sectional study was
      performed on a sample of Moroccan children with psoriasis, in 2014-2016. RESULTS:
      A total of 64 pediatric psoriasis patients had metabolic comorbidities in
      association with psoriasis; 20 children had non-metabolic comorbidities; and 76
      children had no comorbidity. The metabolic comorbidities were as follows:
      abdominal obesity, 40% (n = 64); overweight, 12.5% (n = 20); metabolic syndrome,
      3.7% (n = 6); and dyslipidemia, 3.1% (n = 5); the non-metabolic comorbidities
      were atopy, 4.3% (n = 7); epilepsy, 3.1% (n = 5); celiac disease, 1.8% (n = 3);
      vitiligo, 1.8% (n = 3); alopecia ariata, 0.6% (n = 1); and valvular cardiopathy,
      0.6% (n = 1). No cases of diabetes mellitus, obesity, or high blood pressure were
      recorded. Significant factors associated with metabolic comorbidity were extended
      psoriasis vulgaris >10% (P = 0.01; OR, 2.19), severe psoriasis especially
      pustular and erythroderma (P = 0.018; OR, 2), nail involvement (P = 0.016; OR,
      1.5), face involvement (P = 0.01; OR, 1,59), resistance to topical treatment (P =
      0.003; OR, 2.5) and alteration of quality of life (P = 0.02; OR, 1,7). There was
      no significant risk factor associated with non-metabolic comorbidity.
      CONCLUSIONS: Given the frequent association of pediatric psoriasis with many
      disorders, these comorbidities should be investigated and identified so that they
      can be taken into account in the management of psoriasis in order to avoid
      treatment failure. Regular follow up should be carried out in patients at risk of
      metabolic comorbidity.

PMID- 28452101
TI  - Effects of combined low-dose spironolactone plus vitamin E vs vitamin E
      monotherapy on insulin resistance, non-invasive indices of steatosis and
      fibrosis, and adipokine levels in non-alcoholic fatty liver disease: a randomized
      controlled trial.
AB  - The beneficial effects of mineralocorticoid receptor blockade by spironolactone
      have been shown in animal models of non-alcoholic fatty liver disease (NAFLD).
      The aim of the present 52-week randomized controlled trial was to compare the
      effects of low-dose spironolactone and vitamin E combination with those of
      vitamin E monotherapy on insulin resistance, non-invasive indices of hepatic
      steatosis and fibrosis, liver function tests, circulating adipokines and hormones
      in patients with histologically confirmed NAFLD. Homeostasis model of assessment
      of insulin resistance (HOMA-IR) and non-invasive indices of steatosis and
      fibrosis were calculated. Analysis was intention-to-treat. NAFLD liver fat score,
      an index of steatosis, decreased significantly in the combination treatment group
      (P = .028), but not in the vitamin E group, and the difference for group*time
      interaction was significant (P = .047). Alanine aminotransferase-to-platelet
      ratio index, an index of fibrosis, did not change. Insulin levels and HOMA-IR
      decreased significantly only within the combination group (P = .011 and P = .011,
      respectively). In conclusion, the combined low-dose spironolactone plus vitamin E
      regimen significantly decreased NAFLD liver fat score. Larger-scale trials are
      needed to clarify the effect of low-dose spironolactone on hepatic histology.

PMID- 28452102
TI  - Direct Experimental Evidence for Halogen-Aryl pi Interactions in Solution from
      Molecular Torsion Balances.
AB  - We dissected halogen-aryl pi interactions experimentally using a bicyclic N
      arylimide based molecular torsion balances system, which is based on the
      influence of the non-bonded interaction on the equilibria between folded and
      unfolded states. Through comparison of balances modulated by higher halogens with
      fluorine balances, we determined the magnitude of the halogen-aryl pi
      interactions in our unimolecular systems to be larger than -5.0 kJ mol-1 , which
      is comparable with the magnitude estimated in the biomolecular systems. Our study
      provides direct experimental evidence of halogen-aryl pi interactions in
      solution, which until now have only been revealed in the solid state and
      evaluated theoretically by quantum-mechanical calculations.

PMID- 28452103
TI  - Age-specific risk of renal graft loss from late acute rejection or non-compliance
      in the adolescent and young adult period.
AB  - AIMS: The aims of this study were to identify if an age-specific high-risk window
      for graft loss is present in Australia and New Zealand and identify the aetiology
      for such graft loss using the Australia and New Zealand Dialysis and Transplant
      Registry. METHODS: Retrospective cohort analysis of all renal transplants were
      performed in Australia and New Zealand during 1985-2010 in which the graft
      survived >3 months and the patient spent at least some time aged 10-30 years
      inclusive while the graft was functioning. Adjusted hazard ratio (aHR) for graft
      loss according to age, sex, race, cause of end-stage kidney disease, transition,
      era of transplantation, donor type and human leucocyte antigen mismatch were
      calculated using an extended Cox proportional hazards model for graft loss from
      any cause and graft loss from late acute rejection (LAR) or non-compliance.
      RESULTS: A total of 3289 grafts in 3048 recipients were included. A total of 757
      grafts failed including 110 (15 %) from LAR or non-compliance. Age was strongly
      associated with graft loss from LAR or non-compliance (p < 0.001). Compared with
      age 10-12 years, the risk of graft loss from LAR or non-compliance was
      significantly increased from 16-24 years, peaking at 19-21 years (aHR 11.3, 95%
      confidence interval (CI) 1.5-84.3, p < 0.001). Indigenous race was associated
      with LAR or non-compliance (aHR 3.5, 95% CI 2.1-5.6) whereas paediatric-to-adult
      transition with a functioning transplant was not (aHR 1.2, 95% CI 0.4-3.5, p =
      0.68). CONCLUSION: The high risk of graft loss during adolescence and young
      adulthood is primarily due to LAR or non-compliance. The elevated risk continues
      well into the 20s and is independent of paediatric-to-adult transition.

PMID- 28452104
TI  - Realizing an Aza Paterno-Buchi Reaction.
AB  - Intramolecular atropselective aza Paterno-Buchi reaction involving atropisomeric
      enamide and imine functionalities under sensitized irradiation leads to azetidine
      products in good yield and selectivity (ee >96 %). A mechanistic model based on
      detailed photophysical and isomerization kinetic studies is provided that shed
      light into the reactivity of enamides leading to aza Paterno-Buchi reaction.

PMID- 28452105
TI  - Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and
      Cystargolide.
AB  - Belactosins and cystargolides are natural product proteasome inhibitors from
      Actinobacteria. Both feature dipeptidic backbones and a unique beta-lactone
      building block. Herein, we present a detailed investigation of their
      biosynthesis. Identification and analysis of the corresponding gene clusters
      indicated that both compounds are assembled by rare single-enzyme amino acid
      ligases. Feeding experiments with isotope-labeled precursors and in vitro
      biochemistry showed that the formation of the beta-lactone warhead is
      unprecedented and reminiscent of leucine biosynthesis, and that it involves the
      action of isopropylmalate synthase homologues.

PMID- 28452106
TI  - Electrochemical In Situ Formation of a Stable Ti-Based Skeleton for Improved Li
      Storage Properties: A Case Study of Porous CoTiO3 Nanofibers.
AB  - Bimetallic transition-metal oxides, which exhibit superior electrochemical
      properties compared with pristine single-metal oxides, have recently become a
      topic of significant research interest for applications in lithium-ion batteries
      (LIBs). Herein, we report a simple and scalable electrospinning method to
      synthesize porous CoTiO3 nanofibers as the precursor for nanostructured
      bimetallic transition-metal oxides formed electrochemically in situ. This
      strategy ensures uniform mixing and perfect contact between two constituent
      transition-metal oxides during the lithiation/delithiation process. Furthermore,
      CoTiO3 nanofibers based on ultrafine CoTiO3 nanocrystals are interconnected to
      form a nano/microstructured 3D network, which ensures the high stability of the
      in situ formed structure composed of bimetallic transition-metal oxides, and also
      fast ion/electron transfer and electrolyte penetration into the electrode.
      Electrochemical measurements revealed the excellent lithium storage (647 mAh g-1
      at 0.1 Ag-1 ) and retention properties (600 mAh g-1 at 1 Ag-1 after 1200 cycles)
      of the CoO/TiO2 electrode. Moreover, the electrochemical reaction mechanism was
      explored by using ex situ X-ray photoelectric spectroscopy and cyclic voltammetry
      tests, which confirmed the two-phase reaction processes in the electrodes. These
      results clearly validate the potential of CoTiO3 with a unique
      nano/microstructured morphology as the precursor for a bimetallic transition
      metal oxide for use as the anode material for long-life LIBs.

PMID- 28452107
TI  - Neuroinvasive St. Louis Encephalitis Virus Infection in Solid Organ Transplant
      Recipients.
AB  - In summer 2015, three unrelated solid organ transplant recipients in Phoenix,
      Arizona, had meningoencephalitis suggestive of West Nile virus (WNV) infection.
      Testing was inconclusive but was later confirmed as St. Louis encephalitis (SLE).
      We retrospectively reviewed clinical manifestations, treatment, and outcomes of
      these transplant recipients. Common symptoms were fever, rigors, diarrhea,
      headache, and confusion. One patient died 3 days after hospitalization. Therapy
      for the other two patients was initiated with interferon alpha-2b (IFN) and
      intravenous IgG (IVIG; IFN plus IVIG in combination). Both patients tested
      positive for WNV by serologic assay, but SLE virus (SLEV) infection was later
      confirmed by plaque reduction neutralization test at a reference laboratory.
      Clinical improvement was observed within 72 h after initiation of IFN plus IVIG.
      SLEV has been an uncommon cause of neuroinvasive disease in the United States.
      Accurate, timely diagnosis is hindered because of clinical presentation similar
      to neuroinvasive WNV and SLE, serologic cross-reactivity, and lack of a
      commercially available serologic assay for SLEV. There is currently no approved
      therapy for flaviviral neuroinvasive disease. Anecdotal reports indicate varying
      success with IFN, IVIG, or IFN plus IVIG in WNV neuroinvasive disease. The same
      regimen might be of value for immunocompromised persons with neuroinvasive SLEV
      infection.

PMID- 28452108
TI  - Potential complication of the cruciform trauma position.

PMID- 28452109
TI  - Implications of Albumin Leakage for Survival in Maintenance Hemodialysis
      Patients: A 7-year Observational Study.
AB  - Albumin leakage during hemodialysis (HD) presents a clinical dilemma. However,
      protein-binding uremic toxins are suggested to be responsible for increased
      mortality. No one has investigated the relationship between albumin leakage and
      mortality. Therefore, the purpose of this observational study was to analyze the
      association of albumin leakage with mortality in 690 HD patients who survived one
      year after enrollment. They were divided to three groups who received HD with
      large (3 g or more per HD session), middle (1 to 3 g) or small (less than 1 g)
      amount of albumin leakage, respectively. A propensity score analysis minimizing
      indication bias was performed. Consequently, in a 7-year observation period, 212
      patients died. Albumin leakage 3 g or more per HD session provided better
      prognosis than albumin leakage less than 3 g per HD session. In conclusion,
      clinically acceptable large albumin leakage provides beneficial effects on
      mortality in maintenance HD patients.

PMID- 28452110
TI  - Antimicrobial Effects of Quillaja saponaria Extract Against Escherichia coli
      O157:H7 and the Emerging Non-O157 Shiga Toxin-Producing E. coli.
AB  - Natural alternate methods to control the spread of Shiga toxin-producing
      Escherichia coli (STEC) are important to prevent foodborne outbreaks. Quillaja
      saponaria aqueous bark extracts (QE), cleared by the U.S. Food and Drug
      Administration as a natural flavorant, contain bioactive polyphenols, tannins,
      and tri-terpenoid saponins with anti-inflammatory and antimicrobial activity. The
      objective of this study was to determine the effects of commercial QE against E.
      coli O157:H7 and non-O157 strains over 16 h at 37  degrees C and RT. Overnight
      cultures of 4 E. coli O157:H7 strains and 6 non-O157 STECs in Tryptic Soy Broth
      (TSB) were washed and resuspended in phosphate-buffered saline (PBS, pH 7.2), and
      treated with QE and controls including citric acid (pH 3.75), sodium benzoate
      (0.1% w/w), acidified sodium benzoate (pH 3.75) or PBS for 6 h or 16 h. Recovered
      bacteria were enumerated after plating on Tryptic Soy Agar, from duplicate
      treatments, replicated thrice and the data were statistically analyzed. The 4 QE
      treated E. coli O157:H7 strains from initial ~7.5 log CFU had remaining counts
      between 6.79 and 3.5 log CFU after 16 h at RT. QE-treated non-O157 STECs showed
      lower reductions with remaining counts ranging from 6.81 to 4.55 log CFU after 16
      h at RT.  Incubation at 37  degrees C caused reduction to nondetectable levels
      within 1 h, without any significant reduction in controls. Scanning electron
      microscopy studies revealed damaged cell membranes of treated bacteria after 1 h
      at 37  degrees C. QE shows potential to control the spread of STECs, and further
      research in model food systems is needed.

PMID- 28452112
TI  - Trajectories of well-being during an exercise randomized controlled trial: The
      role of exposure and exercise experiences.
AB  - We examined how process factors were related to the development of various
      indicators of well-being during the course of an exercise randomized controlled
      trial aimed at reducing fatigue among university students. We investigated (a)
      whether actual exposure to the exercise sessions was related to differences in
      students' trajectories of well-being, (b) the minimally required exposure to
      exercise needed before well-being started to differ between the intervention and
      control condition, and (c) whether exercise experiences (enjoyment and
      detachment) were related to differences in well-being trajectories. University
      students with high levels of fatigue were randomly allocated to a 6-week exercise
      intervention (n = 50) or wait list (n = 49). All participants were measured
      before, 5 times during, and at the end of the intervention period. Multilevel
      analyses showed that exercisers with high exposure showed an increase in self
      efficacy whereas those with low exposure did not. Effects of exercise on well
      being became visible after 2 to 4 weeks during the intervention period and
      (partly) depended on the extent of psychological detachment. We recommend that
      both outcomes and process factors throughout the intervention period should be
      measured in order to better understand "when" and "under what conditions" an
      exercise intervention works.

PMID- 28452113
TI  - Zika Virus RNA in an Asymptomatic Donor's Vitreous: Risk of Transmission?

PMID- 28452111
TI  - Epigenetic dysregulation of ID4 predicts disease progression and treatment
      outcome in myeloid malignancies.
AB  - Promoter hypermethylation-mediated inactivation of ID4 plays a crucial role in
      the development of solid tumours. This study aimed to investigate ID4 methylation
      and its clinical relevance in myeloid malignancies. ID4 hypermethylation was
      associated with higher IPSS scores, but was not an independent prognostic
      biomarker affecting overall survival (OS) in myelodysplastic syndrome (MDS).
      However, ID4 hypermethylation correlated with shorter OS and leukaemia-free
      survival (LFS) time and acted as an independent risk factor affecting OS in acute
      myeloid leukaemia (AML). Moreover, ID4 methylation was significantly decreased in
      the follow-up paired AML patients who achieved complete remission (CR) after
      induction therapy. Importantly, ID4 methylation was increased during MDS
      progression to AML and chronic phase (CP) progression to blast crisis (BC) in
      chronic myeloid leukaemia (CML). Epigenetic studies showed that ID4 methylation
      might be one of the mechanisms silencing ID4 expression in myeloid leukaemia.
      Functional studies in vitro showed that restoration of ID4 expression could
      inhibit cell proliferation and promote apoptosis in both K562 and HL60 cells.
      These findings indicate that ID4 acts as a tumour suppressor in myeloid
      malignancies, and ID4 methylation is a potential biomarker in predicting disease
      progression and treatment outcome.

PMID- 28452114
TI  - Critical thinking, curiosity and parsimony in (emergency) medicine: 'Doing
      nothing' as a quality measure?
AB  - Current medical decision-making is influenced by many factors, such as competing
      interests, distractions, as well as fear of missing an important diagnosis. This
      can result in ordering tests or providing treatments that can be harmful.
      Unnecessary tests are more likely to lead to false positive diagnosis or
      incidental findings that are of uncertain clinical relevance. Estimates indicate
      that almost one-third of all health spending is wasteful. The 'Choosing Wisely'
      campaign has identified many of these wasteful tests and treatments. This
      perspective proposes some suggestions to focus on our critical thinking, embrace
      shared decision-making and stay curious about the patient we are treating. Most
      importantly, 'doing nothing' could be a quality indicator for EDs, and ACEM
      supported audits and research to develop benchmarks for certain tests and
      procedures in the ED are important to achieve a cultural change.

PMID- 28452115
TI  - Properties of NeoMTA Plus and MTA Plus cements for endodontics.
AB  - AIM: To test a novel calcium silicate cement mixed with a water-based gel (NeoMTA
      Plus) with regard to chemical-physical properties and apatite-forming ability.
      METHODOLOGY: NeoMTA Plus (Avalon Biomed Inc. Bradenton, FL, USA; lot. 2014090301)
      and a commercial MTA-based material with similar properties (MTA Plus, Prevest
      Denpro Limited, Jammu, India; lot. 41001) were tested for ion-releasing ability,
      initial and final setting times, radiopacity, open and impervious porosity and
      apparent porosity, water sorption, weight loss, solubility, ability to nucleate
      calcium phosphates (CaP) after immersion in HBSS (Hank's Balanced Salt Solution)
      by ESEM-EDX and micro-Raman spectroscopy. The results were analysed statistically
      with the anova test (P  <  0.05). RESULTS: NeoMTA Plus had a prolonged setting
      time (315 min) and a satisfactory radiopacity (3.76 mm Al). Calcium and hydroxyl
      ion release was significantly greater and more prolonged in comparison with MTA
      Plus (P < 0.05). Both NeoMTA Plus and MTA Plus had high values of open porosity
      and solubility. ESEM-EDX and micro-Raman confirmed the ability to nucleate
      calcium phosphates on their surface after immersion in HBSS. CONCLUSION: NeoMTA
      Plus is a new calcium silicate-based cement for root filling with an adequate
      radiopacity and prolonged setting time. The ion release and CaP-forming ability
      could increase stability of the root filling and promote endodontic and
      periodontal tissue regeneration, enhancing the bioactivity and biocompatibility
      of the material.

PMID- 28452116
TI  - Beta-blockers in patients with advanced cirrhosis: Red light, green light, yellow
      light....

PMID- 28452117
TI  - The mentoring manifesto: Advice from a mentor.

PMID- 28452118
TI  - The attitudes of medical students in Europe toward the clinical importance of
      histology.
AB  - Many studies have been undertaken to assess the attitudes of medical students to
      the clinical importance of gross anatomy. However, much less is known about their
      attitudes toward the clinical importance of histology. Using Thurstone and Chave
      methods to assess attitudes, over 2,000 early stage medical students across
      Europe provided responses to a survey that tested the hypothesis that the
      students have a high regard for histology's clinical relevance. Regardless of the
      university and country surveyed, and of the teaching methods employed for
      histology, our findings were not consistent with our hypotheses, students
      providing a more moderate assessment of histology's importance compared to gross
      anatomy but more positive than their attitudes toward embryology. Histology
      should play a significant role in medical education in terms of appreciating not
      just normal structure and function but also pathology. We conclude that teachers
      of histology should pay special attention to informing newly-recruited medical
      students of the significant role played by histology in attaining clinical
      competence and in underpinning their status as being learned members of a
      healthcare profession. This work was conducted under the auspices of the Trans
      European Pedagogic Research Group (TEPARG). Clin. Anat. 30:635-643, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 28452119
TI  - Medical students and measuring blood pressure: Results from the American Medical
      Association Blood Pressure Check Challenge.
AB  - Blood pressure (BP) measurement is the most common procedure performed in
      clinical practice. Accurate BP measurement is critical if patient care is to be
      delivered with the highest quality, as stressed in published guidelines.
      Physician training in BP measurement is often limited to a brief demonstration
      during medical school without retraining in residency, fellowship, or clinical
      practice to maintain skills. One hundred fifty-nine students from medical schools
      in 37 states attending the American Medical Association's House of Delegates
      Meeting in June 2015 were assessed on an 11-element skillset on BP measurement.
      Only one student demonstrated proficiency on all 11 skills. The mean number of
      elements performed properly was 4.1. The findings suggest that changes in medical
      school curriculum emphasizing BP measurement are needed for medical students to
      become, and remain, proficient in BP measurement. Measuring BP correctly should
      be taught and reinforced throughout medical school, residency, and the entire
      career of clinicians.

PMID- 28452120
TI  - Preoxygenation via a non-rebreather mask comparing a standard oxygen flowmeter
      rate of 15 Lpm to maximally open.

PMID- 28452121
TI  - DNA-Origami-Based Assembly of Anisotropic Plasmonic Gold Nanostructures.
AB  - Precise control over the assembly of anisotropic plasmonic gold nanostructures
      with relative spatial directionality and sequence asymmetry remains a major
      challenge and offers great fundamental insight and optical application
      possibilities. Here, a novel strategy is developed to anisotropically
      functionalize gold nanorods (AuNRs) by using a DNA-origami-based precise machine
      to transfer essential DNA sequence configurations to the surface of the AuNRs
      through an intentionally designed toehold-initiated displacement reaction.
      Different AuNR products are examined via hybridization with DNA-AuNPs that
      display distinct elements of regiospecificity. These assembled anisotropic
      plasmonic gold nanostructures based on the DNA-origami precise machine inherit
      the encoded information from the parent platform with high fidelity and show
      fixed orientation and bonding anisotropy, thereby generating discrete plasmonic
      nanostructures with enhanced Raman resonance.

PMID- 28452122
TI  - Identification of Sequence Variants within Experimentally Validated Protein
      Interaction Sites Provides New Insights into Molecular Mechanisms of Disease
      Development.
AB  - Protein interactions (PI) underlie complex biological processes. Protein
      interaction partners include DNA, RNA, ions, small chemical compounds, and
      proteins (protein-protein interactions; PPI). Analysis of sequence variants
      within regions corresponding to experimentally validated PI sites presents novel
      opportunities for understanding of complex diseases. Such information has not
      been systematically collected due to the fact that datasets are dispersed
      throughout databases and publications. Sequence variants and PI regions were
      obtained from the UniProt database. The location of the variants was compared to
      start and end positions of each PPI. Associations of sequence variants with
      phenotype were obtained from databases including COSMIC, GAD, PharmGKB, and
      dbSNP. We developed a catalogue of 603 sequence variants located within regions
      corresponding to experimentally validated PI sites, mostly PPI regions. These
      sequence variants were previously associated with risk for cancer, reproduction,
      ageing, renal, and immune system diseases. The developed catalogue connects
      information from different research papers and databases, represents a new layer
      of information and enables designing new hypotheses. It provides a baseline for
      prioritization of sequence variants, which may affect protein function and
      binding sites. The study contributes to the development of the proteogenomics
      field and provides new insights for understanding molecular mechanisms underlying
      disease development.

PMID- 28452123
TI  - Outcome of three screening questions for temporomandibular disorders (3Q/TMD) on
      clinical decision-making.
AB  - Patients with temporomandibular disorders (TMD) seem to go undetected and not
      adequately managed within dentistry. To identify these patients, three screening
      questions (3Q/TMD) have been introduced within dentistry in parts of Sweden. It
      is not known whether 3Q/TMD affects the clinical decision-making for these
      patients. The aim of this study was to evaluate the outcome of 3Q/TMD on the
      clinical decision-making and to analyse whether gender, age and the fee system
      the individual was assigned to were related to prescribed TMD treatment. This
      cohort study was carried out within the Public Dental Health service in
      Vasterbotten, Sweden. As part of the routine dental check-up, a health
      declaration including 3Q/TMD was completed. The study population was randomly
      selected based on their 3Q/TMD answers. In total, 300 individuals with an
      affirmative answer to any of the 3Q/TMD, and 500 individuals with all negative
      answers were selected. The 3Q/TMD includes questions on weekly jaw-face-temple
      pain (Q1), pain on function (Q2) and catching/locking of the jaw (Q3). The 3Q/TMD
      was analysed in relation to prescribed treatment assessed from dental records.
      There was significantly more treatment performed or recommended for 3Q-positives
      (21.5%), compared to 3Q-negatives (2.2%) (P < 0.001). The odds ratio for TMD
      related treatment for 3Q-positives versus 3Q-negatives was 12.1 (95% CI: 6.3
      23.4). Although affirmative answers to the 3Q/TMD was related to TMD treatment,
      the majority of individuals with a screen positive still did not, according to
      dental records, receive assessment or treatment. Further studies are needed to
      better understand the clinical decision-making process for patients with TMD.

PMID- 28452124
TI  - Synergetic Use of Principal Component Analysis Applied to Normed Physicochemical
      Measurements and GC * GC-MS to Reveal the Stabilization Effect of Selected
      Essential Oils on Heated Rapeseed Oil.
AB  - Lipid oxidation leads to the formation of volatile compounds and very often to
      off-flavors. In the case of the heating of rapeseed oil, unpleasant odors,
      characterized as a fishy odor, are emitted. In this study, 2 different essential
      oils (coriander and nutmeg essential oils) were added to refined rapeseed oil as
      odor masking agents. The aim of this work was to determine a potential
      antioxidant effect of these essential oils on the thermal stability of rapeseed
      oil subject to heating cycles between room temperature and 180  degrees C. For
      this purpose, normed determinations of different parameters (peroxide value,
      anisidine value, and the content of total polar compounds, free fatty acids and
      tocopherols) were carried out to examine the differences between pure and
      degraded oil. No significant difference was observed between pure rapeseed oil
      and rapeseed oil with essential oils for each parameter separately. However, a
      stabilizing effect of the essential oils, with a higher effect for the nutmeg
      essential oil was highlighted by principal component analysis applied on
      physicochemical dataset. Moreover, the analysis of the volatile compounds
      performed by GC * GC showed a substantial loss of the volatile compounds of the
      essential oils from the first heating cycle.

PMID- 28452125
TI  - Stepwise application of fibrosis index based on four factors, red cell
      distribution width-platelet ratio, and aspartate aminotransferase-platelet ratio
      for compensated hepatitis B fibrosis detection.
AB  - BACKGROUND AND AIM: Fibrosis index based on four factors (FIB-4) and aspartate
      aminotransferase-platelet ratio (APRI) were validated with unsatisfactory
      efficiency. Routine hematology index red cell distribution width-platelet ratio
      (RPR) had been tried in liver fibrosis detection. This study tries to evaluate
      the stepwise application of FIB-4, RPR, and APRI in detecting chronic hepatitis B
      (CHB) fibrosis. METHODS: A total of 246 compensated CHB patients who underwent
      liver biopsies, transient elastography, and routine blood tests including
      complete blood count were included. Dual cut-offs were determined to exclude or
      include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers
      including RPR, FIB-4, and APRI were statistically analyzed. RESULTS: The Metavir
      F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of
      the eligible patients, respectively. The area under receiver operating
      characteristics curves for detecting significant fibrosis and cirrhosis were
      0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB-4; 0.638 and
      0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet
      volume-platelet ratio, respectively. The proportion of patient determined as
      cirrhosis or non-cirrhosis was 65.9% by transient elastography, 36.9% by FIB-4,
      30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining
      significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order.
      Detected by stepwise application of FIB-4, RPR, and APRI, 41.5% and 52.8% of
      patients could be determined the state of significant fibrosis and cirrhosis,
      respectively. CONCLUSIONS: In source-limited settings without transient
      elastography, stepwise applying FIB-4, RPR, and APRI could free nearly half of
      CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.

PMID- 28452126
TI  - Plasma proteome of buffaloes.
AB  - The proteomic approach has aroused the interest of veterinary medicine
      researchers, especially regarding the production of biopharmaceuticals and
      diagnosis of diseases in farm animals. Water buffaloes have gained prominence in
      the world economy due to the quality of their milk, meat, and leather, in
      addition to being an important donor of blood components. This work aimed to
      identify and characterize the proteins present in the blood plasma of Murrah
      buffaloes (Bubalus bubalis) through 2D electrophoresis, in gel protein digestion
      followed by mass spectrometry technique and for albumin depletion, in solution
      protein digestion followed by shotgun analysis. Our results showed the
      identification of 112 protein spots and 35 individual proteins, respectively. The
      abundant proteins were represented by albumin, fibrinogen-alpha, fibrinogen-beta,
      fibrinogen-gamma, immunoglobulins in general, alpha-1-antiproteinase, alpha-1B
      glycoprotein, alpha-2-HS-glycoprotein, alpha-macroglobulin, apolipoprotein A1,
      antithrombin-III, endopin 2B, fetuin-B, retinol-binding protein, serotransferrin,
      transthyretin and vitamin D-binding protein. Most of these proteins are related
      to the signaling pathways of the complement system and coagulation cascade. The
      results allowed a better understanding of the protein composition of these blood
      components, thus promoting studies on animal health in the search for molecular
      markers of zoonotic diseases in buffaloes.

PMID- 28452127
TI  - From disaster to development: a systematic review of community-driven
      humanitarian logistics.
AB  - A plethora of untapped resources exist within disaster-affected communities that
      can be used to address relief and development concerns. A systematic review of
      the literature relating to community participation in humanitarian logistics
      activities revealed that communities are able to form ad hoc networks that have
      the ability to meet a wide range of disaster management needs. These structures,
      characterised as Collaborative Aid Networks (CANs), have demonstrated efficient
      logistical capabilities exclusive of humanitarian organisations. This study
      proposes that CANs, as a result of their unique characteristics, present
      alternatives to established humanitarian approaches to logistics, while also
      mitigating the challenges commonly faced by traditional humanitarian
      organisations. Furthermore, CANs offer a more holistic, long-term approach to
      disaster management, owing to their impact on development through their
      involvement in humanitarian logistics. This research provides the foundation for
      further theoretical analysis of effective and efficient disaster management, and
      details opportunities for policy and practice.

PMID- 28452128
TI  - Two Perturbations for Geometry Optimization of Off-lattice Bead Protein Models.
AB  - Referring to the optimization algorithm previously developed for atomic clusters,
      the present author develops an efficient method for geometry optimization of a
      coarse-grained protein model expressed with two kinds of beads (hydrophilic and
      hydrophobic ones). In the method, two types of geometrical perturbations, center
      directed bead move and one bead rotation, are used to explore new configurations
      and local optimizations are performed after the perturbations. The center
      directed bead move is used for hydrophobic beads and the one bead rotation is
      performed for both hydrophobic and hydrophilic beads. The optimization method was
      applied to protein models consisting of 13, 20, 21, and 34 beads. The present
      method produced the global minima of the 13-, 21-, and 34-bead models reported in
      the literature and updated the lowest energies of the protein models with 20
      beads. These results indicate that the present method is efficient for searching
      for optimal structures of proteins.

PMID- 28452129
TI  - Studies on the Bioactivities of ACE-inhibitory Peptides with Phenylalanine C
      terminus Using 3D-QSAR, Molecular Docking and in vitro Evaluation.
AB  - 3D-QSAR, molecular docking and activity evaluation were used to study the
      bioactivities of ACE-inhibitory peptides with phenylalanine C-terminus. Both
      CoMFA (Q2 =0.773, R2 =0.992) and CoMSIA (Q2 =0.664, R2 =0.990) models were
      constructed. According to the established models, four novel potent ACE
      inhibitory tripeptides GEF, VEF, VRF, and VKF were synthesized. The IC50 values
      were respectively determined to be 13 MUM, 23 MUM, 5 MUM, and 11 MUM by in vitro
      evaluation. The results show good agreement with the predicted values. The
      established models play an important role in revealing the structure-activity
      relationship of ACE-inhibitory peptides and designing novel peptides with
      enhanced biological activity.

PMID- 28452131
TI  - The influence of variation in parental height dimorphism on same-sex parent
      offspring height differences.
AB  - OBJECTIVE: This study evaluates how adjusting for parental height dimorphism
      influences height differences among parents and same-sex offspring distinguished
      by parents' early backgrounds. PARTICIPANTS AND METHODS: Regression analyses
      using data from independent groups of Taiwanese families, 56 with sons and 51
      with daughters, evaluate how adjusting for parental height dimorphism influences
      same-sex parent-offspring height differences among families grouped by
      grandfathers' occupations into three status categories reflecting good to
      relatively poor early parental environments. RESULTS: Parental height dimorphism
      was statistically significantly associated with same-sex parent-offspring height
      differences (father-son: mean Delta = 3.88 cm, beta = -71.47 +/- 11.49 SE, t = 
      6.22, p <= .0005; mother-daughter: mean Delta = 4.15 cm, beta = 80.46 +/- 18.52
      SE, t = 4.35, p <= .0005). Adjusted mean father-son differences increased
      significantly across grandfathers' occupation categories (Privileged, Delta =
      0.60, Business, Delta = 4.06, Farming & Labor, Delta = 5.28; p = .011). Mother
      daughter differences were substantial, from 3.33 cm to 5.06 cm, but did not
      differ significantly across occupational categories (p = .63). DISCUSSION:
      Adjustments here for variation in parent height dimorphism did not alter original
      interpretations that while female growth may be more canalized, it is similarly
      capable of responding to improvements in developmental contexts. Patterns of same
      sex parent-offspring height differences across grandfathers' occupational
      categories remain best accounted for by Taiwan's rapidly expanding economy,
      substantial income equity and reductions in biases favoring sons over daughters.
      Adjustment for sub-group variation in parental height dimorphism should be
      considered in similar studies in the future.

PMID- 28452130
TI  - Anorexia of ageing: a key component in the pathogenesis of both sarcopenia and
      cachexia.
AB  - The anorexia of aging was first recognized as a physiological syndrome 30 years
      ago. Its major causes are an alteration in fundal compliance with an increase in
      antral stretch and enhanced cholecystokinin activity leading to increased
      satiation.This anorexia leads to weight loss in aging persons and is one of the
      component causes of the aging related sarcopenia. This physiological anorexia
      also increases the risk of more severe anorexia when an older person has an
      increase in inflammatory cytokines such as occurs when they have an illness. This
      results in an increase in the anorexia due to cachexia in older persons.

PMID- 28452132
TI  - Blood-based protein biomarkers for stroke differentiation: A systematic review.
AB  - Computed tomography (CT) scan is the mainstay for diagnosis of stroke; but the
      facility of CT scan is not easily available. A blood-based biomarker approach is
      required to distinguish ischemic stroke (IS) from hemorrhagic stroke (HS) in pre
      hospital settings.To conduct a systematic review of diagnostic utility of blood
      biomarkers for differential diagnosis of stroke.A comprehensive literature search
      was carried out till March 7, 2017 in PubMed, Cochrane, Medline, OVID, and Google
      Scholar databases. Methodological quality of each study was assessed using the
      modified Quality Assessment of Diagnostic Accuracy Studies questionnaire.Eighteen
      studies were identified relevant to our systematic review. Ten single biomarkers
      and seven panels of different biomarkers were identified which showed potential
      for differentiating IS and HS. Activated Protein C- Protein C Inhibitor Complex
      (APC-PCI) (sensitivity-96%), Glial Fibrillary Acidic Protein (GFAP) (specificity
      100%) and a panel of APC-PCI & GFAP (sensitivity- 71%) and Retinol Binding
      Protein 4 (RBP4) & GFAP (specificity- 100%) were found to have high sensitivity
      and specificity for differentiating the two stroke types.Our systematic review
      does not recommend the use of any blood biomarker for clinical purposes yet based
      on the studies conducted till date.

PMID- 28452133
TI  - Blinded ultrasound fetal biometry at 36 weeks and risk of emergency Cesarean
      delivery in a prospective cohort study of low-risk nulliparous women.
AB  - OBJECTIVES: To compare the association between risk of emergency Cesarean
      delivery (CD) and non-customized vs customized ultrasound estimated fetal weight
      (EFW) at 36 weeks' gestation, determine whether addition of ultrasound EFW to a
      model based on maternal characteristics alone improved prediction of emergency
      CD, assess the screening performance of a multivariable model using both EFW and
      maternal characteristics to predict emergency CD, and determine whether women at
      high predicted risk of emergency CD based on this model had higher risk of
      maternal and perinatal morbidity compared with screen-negative women. METHODS: We
      studied 3047 low-risk (no pre-existing medical conditions or acquired
      complications of pregnancy) nulliparous women from the prospective Pregnancy
      Outcome Prediction study (Cambridge, UK) cohort, who underwent ultrasound EFW at
      ~36 weeks' gestation. Both the women and their clinicians were blinded to fetal
      biometry results. Emergency CD was defined as delivery by Cesarean section in
      pregnancies in which the date of delivery had not been prearranged. Additional
      candidate predictors of emergency CD evaluated were maternal age, height, body
      mass index (BMI), weight gain, fetal abdominal circumference growth velocity and
      fetal sex. External validation of the predictive model was performed using
      routinely collected data from 55 337 births in Scotland between 2003 and 2008.
      Women with an estimated risk of emergency CD >= 40% were defined as screen
      positive. RESULTS: Blinded EFW was associated strongly with the risk of emergency
      CD (coefficient for increase of 1 SD in EFW, 0.39 (95% CI, 0.30-0.48); odds ratio
      (OR), 1.48 (95% CI, 1.35-1.62)). The coefficient for customized EFW was similar
      (0.42 (95% CI, 0.33-0.51); OR, 1.53 (95% CI, 1.39-1.67)); hence, for simplicity,
      non-customized EFW was employed subsequently. A multivariable logistic regression
      model combining maternal characteristics (age, height, BMI and weight gain
      between 12 and 36 weeks) was moderately predictive of emergency CD (area under
      the receiver-operating characteristics curve (AUC) = 0.68). Addition of blinded
      EFW to the model increased the AUC to 0.71 and improved prediction (likelihood
      ratio test P < 0.0001). Based on this model, 189 (6.2%) women were screen
      positive and 48% of these delivered by CD. Screen-positive women had elevated
      risks of severe postpartum hemorrhage (relative risk (RR), 2.49; 95% CI, 1.83
      3.38), any adverse neonatal outcome (RR, 1.86; 95% CI, 1.22-2.82) and severe
      adverse neonatal outcome (RR, 4.03; 95% CI, 1.35-12.03) compared with screen
      negative women. The risks of these events were also higher compared with women
      who had a term CD for breech presentation. The model was similarly predictive of
      the risk of emergency CD and perinatal morbidity when evaluated using the dataset
      from Scotland. CONCLUSIONS: Ultrasound EFW at 36 weeks, combined with maternal
      characteristics, can identify women who are at increased risk of subsequent
      emergency CD. These women are at increased risk of maternal and perinatal
      morbidity compared with women at low risk of emergency CD and those having CD for
      breech presentation at term. Copyright (c) 2017 ISUOG. Published by John Wiley &
      Sons Ltd.

PMID- 28452134
TI  - Reply from Joachim Nielsen, Kasper D. Gejl and Niels Ortenblad.

PMID- 28452135
TI  - Reply from Louise M. Burke.

PMID- 28452136
TI  - Overview of The Journal of Physiology Special Issue on the 'Biomedical basis of
      elite performance'.

PMID- 28452137
TI  - Is there plasticity in mitochondrial cristae density with endurance training?

PMID- 28452138
TI  - Methodological issues question the validity of observed performance impairment of
      a low carbohydrate, high fat diet.

PMID- 28452139
TI  - Low versus high carbohydrates in the diet of the world-class athlete: insights
      from McArdle's disease.

PMID- 28452140
TI  - Preparation, Structural Determination, and Characterization of Electronic
      Properties of [5,6]- and [6,6]-Carbosilylated Sc3 N@Ih -C80.
AB  - Photochemical carbosilylation of Sc3 N@Ih -C80 with silirane 1 afforded two
      corresponding [5,6]-adducts, 2 and 3, and a [6,6]-adduct, 4. The structural and
      electronic properties of these products were characterized by means of
      spectroscopic, electrochemical, and theoretical methods. The structure of 2 was
      disclosed by means of single-crystal X-ray crystallographic analysis. Thermal
      isomerization of 3 to 2 was observed, whereas that of 2 to 3 proceeded less
      efficiently at 100  degrees C. Upon heating under the same conditions, adduct 4
      underwent facile decomposition to afford Sc3 N@Ih -C80 , or isomerized into small
      amounts of 2 and 3. The relative stabilities of 2, 3, and 4 were rationalized
      through the results of theoretical calculations. In contrast, adducts 2, 3, and 4
      were stable under the photolytic conditions employed for carbosilylation. The
      photochemical functionalization of Sc3 N@Ih -C80 represents a convenient
      synthetic method to obtain thermally labile fullerene-based products.

PMID- 28452141
TI  - A nurse practitioner-led community workshop: Increasing adult participation in
      advance care planning.
AB  - BACKGROUND AND PURPOSE: Advance directives (ADs) and advance care planning (ACP)
      aid in expressing an individual's preferences and guide future medical decision
      making. Despite the potential of ADs and ACP to positively impact care,
      consistently low rates of ADs and ACP (5%-39%) have been documented. The purpose
      of this project was to increase understanding and participation in the ACP
      process among rural-dwelling community members. METHODS: A pre-post repeated
      measures design with an evaluation component to measure understanding,
      completion, discussion, and dissemination of ADs and ACP. A sample of N = 40 were
      recruited to participate in a one-time nurse practitioner-led Five Wishes
      workshop delivered in a community setting. CONCLUSIONS: Postworkshop evaluations
      indicated an overall acceptance and understanding of ADs and ACP. Completion
      rates of ADs and discussion in the ACP process significantly increased at 1-month
      follow-up. IMPLICATIONS FOR PRACTICE: Nurses and advanced practice nurses are
      well positioned to educate individuals and facilitate the ACP process. There is a
      need to educate individuals on importance of sharing their AD wishes with their
      family and primary care provider. This nurse practitioner-led workshop using the
      Five Wishes demonstrated the feasibility and potential effectiveness of
      initiating the ACP process in the community.

PMID- 28452142
TI  - Impact of sleep, fatigue, and systemic inflammation on neurocognitive and
      behavioral outcomes in long-term survivors of childhood acute lymphoblastic
      leukemia.
AB  - BACKGROUND: Long-term survivors of childhood acute lymphoblastic leukemia (ALL)
      are at risk for neurocognitive impairment, which may be associated with fatigue,
      sleep problems, systemic inflammation, and oxidative stress. We examined these
      associations among survivors of childhood ALL treated with chemotherapy only.
      METHODS: Survivors of childhood ALL (male, n = 35 and female, n = 35; mean age,
      14.3 years [standard deviation, 4.7 years] and mean years from diagnosis, 7.4
      years [standard deviation, 1.9 years]) completed neurocognitive testing,
      behavioral ratings, and reported sleep quality and fatigue symptoms 5 years after
      diagnosis. Serum was collected concurrently and assayed for interleukin (IL)
      1beta and IL-6, tumor necrosis factor alpha (TNF-alpha), high-sensitivity C
      reactive protein (hsCRP), malondialdehyde, myeloperoxidase, and oxidized low
      density lipoprotein. General linear modeling was used to assess associations
      among biomarkers and functional outcomes, adjusting for age and stratified by
      sex. RESULTS: Survivors performed worse than population norms on executive
      function and processing speed and reported more behavioral problems (P < .05
      adjusted for multiple comparison). In female survivors, fatigue was associated
      with poor executive function (r = 0.41; P = .02), processing speed (r = 0.56; P <
      .001), and attention (r = 0.36-0.55; P < .05). Female survivors with frequent
      nighttime awakening displayed more inattention (P = .01), hyperactivity (P =
      .03), and aggression (P = .01). Worse executive function, processing speed, and
      behavioral symptoms were observed in female survivors with higher levels of IL-6,
      IL-1beta, and hsCRP (P < .05). Male survivors with high levels of TNF-alpha
      demonstrated worse organization (P = .03), but no significant associations
      between neurocognitive outcomes and sleep/fatigue measures were observed.
      CONCLUSION: Neurocognitive function in female survivors of childhood ALL appears
      more susceptible to the effects of sleep disturbance and fatigue. Systemic
      inflammation may play a role in neurocognitive impairment and behavioral
      symptoms. Cancer 2017;123:3410-9. (c) 2017 American Cancer Society.

PMID- 28452143
TI  - ZY15557, a novel, long acting inhibitor of dipeptidyl peptidase-4, for the
      treatment of Type 2 diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Dipeptidyl peptidase (DPP)-4 inhibitors increase levels
      of glucagon-like peptide-1 (GLP-1) and provide clinical benefit in the treatment
      of type 2 diabetes mellitus. As longer acting inhibitors have therapeutic
      advantages, we developed a novel DPP-4 inhibitor, ZY15557, that has a sustained
      action and long half-life. EXPERIMENTAL APPROACH: We studied the potency,
      selectivity, efficacy and duration of action of ZY15557, in vitro, with assays of
      DPP-4 activity. In vivo, the pharmacodymamics and pharmacokinetics of ZY15557
      were studied, using db/db mice and Zucker fatty rats, along with normal mice,
      rats, dogs and non-human primates. KEY RESULTS: ZY15557 is a potent, competitive
      and long acting inhibitor of DPP-4 (Ki 5.53 nM; Koff 3.2 * 10-4 .s-1 , half-life
      35.8 min). ZY15557 treatment inhibited DPP-4 activity, and enhanced active GLP-1
      and insulin in mice and rats, providing dose-dependent anti-hyperglycaemic
      effects. Anti-hyperglycaemic effects were also observed in db/db mice and Zucker
      fatty rats. Following oral dosing, ZY15557 significantly inhibited plasma DPP-4
      activity, determined ex vivo, in mice and rats for more than 48 h, and for up to
      168 h in dogs and non-human primates. Allometric scaling predicts a half-life for
      ZY15557 in humans of up to 60 h. CONCLUSIONS AND IMPLICATIONS: ZY15557 is a
      potent, competitive and long acting DPP-4 inhibitor. ZY15557 showed similar DPP-4
      inhibition across different species. ZY15557 showed excellent oral
      bioavailability in preclinical species. It showed a low plasma clearance (CL) and
      large volume of distribution (Vss ) across species, resulting in an extended half
      life.

PMID- 28452144
TI  - Special needs hurricane shelters and the ageing population: development of a
      methodology and a case study application.
AB  - Recent experience of hurricanes, particularly in the southeast United States, has
      heightened awareness of the multifaceted nature of and the challenges to
      effective disaster relief planning. One key element of this planning is providing
      adequate shelter at secure locations for people who evacuate. Some of these
      individuals will have 'special needs', yet there is little research on the
      relationship with shelter space. This study designed a geographic information
      systems-based network optimisation methodology for the siting of special needs
      hurricane relief shelters, with a focus on the transportation component. It
      sought to find new locations for shelters that maximise accessibility by
      vulnerable populations, given capacity constraints, concentrating on the ageing
      population. The framework was implemented in a medium-sized metropolitan
      statistical area in the state of Florida where data suggest a possible deficit in
      special needs shelter space. The study analysed options for increasing special
      needs shelter capacity, while considering potential uncertainties in
      transportation network availability.

PMID- 28452145
TI  - How to manage chronic urticaria 'beyond' guidelines: a practical algorithm.
AB  - Chronic urticaria (CU) is a disease characterized by pruritic weals, angio-oedema
      or both occurring for at least 6 weeks. It encompasses spontaneous and inducible
      urticarias. The national and international guidelines outline the principles of
      treatment. Omalizumab, an anti-immunoglobulin E monoclonal antibody, has
      transformed the management of many severe and treatment-refractory patients.
      However, current UK guidance on its use does not address the needs of those with
      less severe disease, inducible urticarias, idiopathic histaminergic angio-oedema
      without weals as a presentation of CU and omalizumab non-responders. Our
      algorithm and a summary of the evidence to support its principles offers guidance
      and a more systematic targeted approach to using a range of 'off-label' agents
      for specific phenotypes of CU. It will be of use when guideline-recommended mast
      cell mediator antagonists fail to control symptoms and/or using omalizumab is
      ineffective, not practical or unfunded.

PMID- 28452146
TI  - Autonomic testing for prediction of competition performance in Paralympic
      athletes.
AB  - While we now appreciate that autonomic dysfunction can impact wheelchair rugby
      performance, this is currently not being assessed during classification, largely
      due to lack of a standardized and evidence-based strategy to assess autonomic
      function. Our aim, therefore, was to establish the optimal autonomic testing
      protocol that best predicts cardiovascular capacity during competition by
      comprehensively examining autonomic function in elite wheelchair rugby athletes
      with cervical SCI and thereby enhance the standardized classification. Twenty-six
      individuals with cervical SCI (C4-C8; AIS A, B, C) participated in this study
      during the 2015 Parapan American Games in Toronto, Canada. Clinic autonomic
      testing included: sympathetic skin responses, baseline hemodynamics, orthostatic
      challenge test, and cold-pressor tests. Further, we completed standard
      motor/sensory assessments and obtained each participants' International
      Wheelchair Rugby Federation classification. These clinic metrics were correlated
      to in-competition heart rate monitoring obtained during competition. The current
      study provides novel evidence that the change in systolic blood pressure during
      an orthostatic challenge test predicts approximately 50% of the in-competition
      peak heart rate (P<.001). Conversely, International Wheelchair Rugby Federation
      classification was poorly associated with in-competition peak heart rate (R2
      =.204; P<.05). Autonomic testing provides deep insight regarding preserved
      autonomic control after SCI that is associated with performance in elite
      wheelchair rugby athletes. As such, incorporating assessments of cardiovascular
      capacity in classification will help to ensure a level playing field and may
      obviate the need for practices such as boosting to gain an advantage due to poor
      cardiovascular control.

PMID- 28452147
TI  - Achieving Ultrahigh Energy Density and Long Durability in a Flexible Rechargeable
      Quasi-Solid-State Zn-MnO2 Battery.
AB  - Advanced flexible batteries with high energy density and long cycle life are an
      important research target. Herein, the first paradigm of a high-performance and
      stable flexible rechargeable quasi-solid-state Zn-MnO2 battery is constructed by
      engineering MnO2 electrodes and gel electrolyte. Benefiting from a poly(3,4
      ethylenedioxythiophene) (PEDOT) buffer layer and a Mn2+ -based neutral
      electrolyte, the fabricated Zn-MnO2 @PEDOT battery presents a remarkable capacity
      of 366.6 mA h g-1 and good cycling performance (83.7% after 300 cycles) in
      aqueous electrolyte. More importantly, when using PVA/ZnCl2 /MnSO4 gel as
      electrolyte, the as-fabricated quasi-solid-state Zn-MnO2 @PEDOT battery remains
      highly rechargeable, maintaining more than 77.7% of its initial capacity and
      nearly 100% Coulombic efficiency after 300 cycles. Moreover, this flexible quasi
      solid-state Zn-MnO2 battery achieves an admirable energy density of 504.9 W h kg
      1 (33.95 mW h cm-3 ), together with a peak power density of 8.6 kW kg-1 ,
      substantially higher than most recently reported flexible energy-storage devices.
      With the merits of impressive energy density and durability, this highly flexible
      rechargeable Zn-MnO2 battery opens new opportunities for powering portable and
      wearable electronics.

PMID- 28452148
TI  - Understanding structure-function relationships of the human neuronal
      acetylcholine receptor: insights from the first crystal structures of neuronal
      subunits.
AB  - : Nicotinic ACh receptors (nAChRs) are the best studied members of the
      superfamily of pentameric ligand-gated ion channels (pLGICs). Neuronal nAChRs
      regulate neuronal excitability and neurotransmitter release in the nervous system
      and form either homo- or hetero-pentameric complexes with various combinations of
      the 11 neuronal nAChR subunits (alpha2-7, alpha9, alpha10 and beta2-4) known to
      exist in humans. In addition to their wide distribution in the nervous system,
      neuronal nAChRs have been also found in immune cells and many peripheral tissues.
      These nAChRs are important drug targets for neurological and neuropsychiatric
      diseases (e.g. Alzheimer's, schizophrenia) and substance addiction (e.g.
      nicotine), as well as in a variety of diseases such as chronic pain, auditory
      disorders and some cancers. To decipher the functional mechanisms of human nAChRs
      and develop efficient and specific therapeutic drugs, elucidation of their high
      resolution structures is needed. Recent studies, including the X-ray crystal
      structures of the near-intact alpha4beta2 nAChR and of the ligand-binding domains
      of the alpha9 and alpha2 subunits, have advanced our knowledge on the detailed
      structure of the ligand-binding sites formed between the same and different
      subunits and revealed many other functionally important interactions. The aim of
      this review is to highlight some of the structural and functional findings of
      these studies and to compare them with recent breakthrough findings on other
      pLGIC members and earlier data from their homologous ACh-binding proteins. LINKED
      ARTICLES: This article is part of a themed section on Nicotinic Acetylcholine
      Receptors. To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

PMID- 28452149
TI  - Protein Extraction from Porcine Myocardium Using Ultrasonication.
AB  - Porcine myocardium is regarded as a byproduct in slaughterhouses and is rarely
      used as a food source due to its unsuitability for processing and consumption. In
      this study, we sought to develop an efficient ultrasonication method to extract
      protein from porcine myocardium. Comparisons of protein yield using various
      ultrasonication conditions with porcine myocardium revealed that treatment with
      0.2 M NaCl, with pH 8.0, at an extraction temperature of less than 40  degrees C
      and an amplitude of 60% to 80% was optimal, yielding an extraction rate of 90%.
      In addition, SDS-PAGE analysis showed that increasing the time interval for
      ultrasonication increased the presence of myosin heavy chain and actin protein
      content. Functional analysis of the physiological properties of the isolated
      proteins using an ATPase assay showed that Ca and Mg ATPase activity was
      virtually undetectable in the early stages of ultrasonic treatment and that the
      proteins denatured rapidly. An analysis of protein digestion also showed that the
      digestive capacity of proteins treated by ultrasonication methods was greater.
      These results demonstrate that the ultrasonication method is effective for high
      yield protein extraction from cardiac myofibrils of porcine myocardium with low
      salt concentrations, low Ca and Mg ATPase activities, and high digestive
      capacities.

PMID- 28452150
TI  - The moral sense of humanitarian actors: an empirical exploration.
AB  - This paper examines humanitarianism's moral positioning above private and
      political interests to save lives and alleviate suffering. It does not aim to
      assess the legitimacy of this stance, but rather to probe the way in which
      humanitarian actors relate to this moral dimension in their everyday work. It
      investigates empirically humanitarian ethics from the perspective of humanitarian
      actors, drawing on interviews conducted in Beirut, Lebanon, in 2014. As it is
      exploratory, three key conceptual innovations were required. The first of these
      is the introduction of the tools developed to consider a neglected reality:
      humanitarian actors' 'moral sense' vis-a-vis the humanitarian sector's 'moral
      culture'. Second, the study shows how the sector's moral culture is structured
      around the notion of 'concern for persons in need'. Third, it analyses the way in
      which the sector and its actors handle the asymmetrical relationships encountered
      daily. Ultimately this paper seeks to valorise humanitarian actors' creativity in
      their common practices and explore potential challenges to it.

PMID- 28452151
TI  - PK-guided personalized prophylaxis with Nuwiq(r) (human-cl rhFVIII) in adults
      with severe haemophilia A.
AB  - INTRODUCTION: Nuwiq(r) (human-cl rhFVIII) is a 4th generation recombinant human
      FVIII, without chemical modification or protein fusion, produced in a human cell
      line. AIMS/METHODS: This study (NuPreviq) was a prospective, open-label,
      multicentre, phase IIIb study of the efficacy and safety of personalized
      prophylaxis with Nuwiq(r) in 66 previously treated adults with severe haemophilia
      A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3
      month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis
      phase. The personalized prophylaxis regimen was based on individual PK modelling
      for each patient according to whether their PK profile most closely fitted a two-
      or one-compartment model (NuPreviq approach). In cases of uncertainty, a
      noncompartment model was applied. RESULTS: The median dosing interval during
      personalized prophylaxis was 3.5 days, with 57% of patients on <=2 weekly dosing.
      Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median
      [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0,
      0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds.
      During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free.
      Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by
      7.2% from 100.0 to 92.8 IU kg-1 during the last 2 months of personalized
      prophylaxis. There were no FVIII inhibitors or treatment-related serious or
      severe adverse events. CONCLUSION: PK-guided personalized prophylaxis with
      Nuwiq(r) provided bleeding protection and enabled the dosing interval to be
      extended to twice weekly or less in many patients and an overall dose reduction.

PMID- 28452152
TI  - Oxidative deterioration of pork during superchilling storage.
AB  - BACKGROUND: In superchilling (SC), meat is kept at temperatures around 1  degrees
      C below its initial freezing point, leading to a significant increase in shelf
      life. This study aimed to address the oxidative changes taking place in pork
      loins during prolonged storage at SC temperature. Loins were stored either at
      chilling (CH) conditions (2-4  degrees C) for 4 weeks or at SC temperature
      (around -1  degrees C) for 12 weeks. RESULTS: Storage at SC temperature
      diminished the rate of lipid and protein oxidation and discoloration in pork
      loins, so that final levels of most oxidation products and instrumental color
      values after 12 weeks of SC storage were similar to those after 4 weeks at CH
      conditions. However, hexanal content peaked by the end of SC storage, pointing to
      a potential accumulation of compounds from lipid oxidation during SC storage.
      CONCLUSION: SC storage of pork slows down the rate of lipid and protein
      oxidation. However, accumulation of volatile compounds from lipid oxidation could
      be a limiting factor for shelf life. (c) 2017 Society of Chemical Industry.

PMID- 28452154
TI  - Genetic and environmental factors influence Listeria monocytogenes nisin
      resistance.
AB  - AIMS: Listeria monocytogenes nisin resistance increases when first exposed to
      NaCl and other stresses, such as low pH. In addition to environmental stressors,
      specific genomic elements can confer nisin resistance, such as the stress
      survival islet (SSI-1). As SSI-1 is variably present among L. monocytogenes
      strains, we wanted to determine if SSI-1 was associated with salt-induced nisin
      resistance. METHODS AND RESULTS: The presence of SSI-1 was determined using PCR
      for 48 strains of L. monocytogenes. When combined with multilocus sequence typing
      data, we found that the distribution of SSI-1 is clonal, where strains from
      clonal complexes (CC) 2, 6 and 11 do not have SSI-1, while strains from CCs 3, 5,
      7 and 9 contain SSI-1. The impact of SSI-1 on salt-induced nisin resistance was
      dependent on CC. The average log decrease after 24 h of exposure to nisin at 7
      degrees C under salt-inducing conditions was 2.6 +/- 1.1 for CC 9 strains and 2.3
      +/- 0.7 for CC 11 strains, which had significantly lower survival compared to the
      other CCs, such as 1.3 +/- 0.3 for CC 6. Deletion of SSI-1 from a CC 7 strain
      demonstrated the role SSI-1 plays in salt-induced nisin resistance, as the
      deletion mutant had lower resistance compared to the parent strain. CONCLUSIONS:
      These data suggest that inducible nisin resistance in L. monocytogenes can be
      influenced by environmental conditions as well as the genetic composition of the
      strain, which should be considered when selecting control measures for ready-to
      eat foods. SIGNIFICANCE AND IMPACT OF THE STUDY: The foodborne pathogen L.
      monocytogenes can grow in suboptimal conditions, including low temperature and
      high osmolarity, which makes it a safety concern for ready-to-eat foods. When
      using antimicrobial peptide inhibitors such as nisin, it is important to
      understand how food components can impact antimicrobial resistance across the
      genetic diversity of L. monocytogenes.

PMID- 28452153
TI  - Bioinspired Solid Organogel Materials with a Regenerable Sacrificial Alkane
      Surface Layer.
AB  - In nature, lifetime-long functionalities of land plant leaves rely on the
      regenerability as well as the solid feature of the epicuticular wax layer.
      Inspired by the regenerable solid epicuticular wax on land plant leaf surfaces,
      herein a type of solid organogel material with regenerable sacrificial alkane
      surface layer is reported. This type of surface material is demonstrated to be of
      great practical importance for tackling solid deposition, such as anti-icing,
      antigraffiti, and antifouling, since the deposited foreign materials can be
      easily removed together with the alkane surface layer. Significantly, the solid
      alkane layer does not contaminate nearby surfaces due to its solid nature in both
      working and stand-by conditions, which is completely different to liquid-infused
      materials.

PMID- 28452155
TI  - Silicon-substituted Xanthene Dyes and Their Unique Photophysical Properties for
      Fluorescent Probes.
AB  - Silicon-substituted xanthene dyes, with Si in place of the O atom at the xanthene
      10-position, are practically useful as far-red to near-infrared fluorophores.
      Many fluorescent probes based on them have recently been reported. These
      fluorophores retain the advantages of typical xanthene dyes and also show unique
      properties suitable for applications such as multi-color and super-resolution
      imaging.

PMID- 28452156
TI  - Understanding follicle growth in vitro: Are we getting closer to obtaining mature
      oocytes from in vitro-grown follicles in human?
AB  - Obtaining and fertilizing mature oocytes from immature follicles that were grown
      outside the body has conceptually attracted scientists for centuries, with
      initial attempts first documented in the 19th century. Significant progress has
      been made since then, due in part to a better understanding of folliculogenesis
      and improved techniques of in vitro follicle growth. Indeed, in vitro growth is
      now considered a reasonable approach to preserve or restore fertility when
      immature follicles and their oocytes need to be grown and matured outside the
      body. Certain patients would benefit from in vitro follicle growth, particularly
      those who carry a risk of cancer re-seeding after grafting of frozen-thawed
      ovarian tissue or who are at the risk of premature ovarian failure due to several
      intrinsic ovarian defects and genetic mutations that lead to accelerated follicle
      atresia and early exhaustion of the ovarian reserve. This review provides an
      update on the current status of in vitro growth of preantral human follicles,
      from initial efforts to the most recent achievements.

PMID- 28452157
TI  - Facilitating anaplastic thyroid cancer specialized treatment: A model for
      improving access to multidisciplinary care for patients with anaplastic thyroid
      cancer.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid
      cancer. Several treatment trials are available, but the number of eligible
      patients to participate is very low because of the rarity and aggressiveness of
      the disease. METHODS: Facilitating Anaplastic Thyroid Cancer Specialized
      Treatment (FAST) is a quality improvement project aimed at decreasing time from
      referral to disposition (scheduling of first appointment) to our institution.
      After identifying reasons for delays, we created a new process flow specifically
      for patients with ATC allowing patients to be scheduled immediately. RESULTS:
      Historical data revealed a mean referral to disposition time for patients with
      ATC of 8.7 days before our intervention. After the intervention, the mean
      referral to disposition time was reduced to 0.5 days. Participation in treatment
      trials for all patients with ATC was 34%. CONCLUSION: Since the implementation of
      FAST, the access time has decreased and the number of successful referrals for
      ATC has increased significantly.

PMID- 28452158
TI  - Consistency stability of water thickened with maltodextrin, xanthan gum and
      potassium chloride.
AB  - : Thickened water used for hydration of patients with dysphagia and airway
      aspiration may change its consistency after preparation. The objective of this
      investigation was to evaluate the consistency stability of water thickened with
      maltodextrin, xanthan gum, and potassium chloride using the method developed by
      the International Dysphagia Diet Standardization Initiative (IDDSI). The IDDSI
      flow test consists of placing 10 ml of liquid inside a graduated syringe and
      measuring how much volume remains after a flow duration of 10 s. Pure and
      thickened water was tested with 1.2 g (nectar), 2.4 g (honey), and 3.6 g
      (pudding) of food thickener in 100 ml of water. Each consistency was measured at
      8 a.m. ten times immediately after preparation, and hourly for 12 hr (from 8 a.m.
      to 8 p.m.), and every 24 hr for 96 hr, always at 8 a.m. With the thin liquid,
      nothing was left in the syringe at 10 s (zero), with the consistency nectar, the
      volume remaining was 5.43(0.64) ml (level 2, mildly thick), with the consistency
      of honey, 8.14(0.57) ml remained (level 3, moderately thick), and with the
      consistency pudding 9.48(0.07) ml (level 3, moderately thick). There was a small
      increase in consistency after 10 hr of the preparation. The consistency changed
      after 24 hr in preparations with mildly thick consistency (level 2) and after 48
      hr with the moderately thick consistency (level 3). In conclusion, there was good
      stability of the thickened water at least during a 12-hr period. PRACTICAL
      APPLICATIONS: This investigation demonstrated that thickened water with 1.2, 2.4,
      and 3.6 g of thickener with maltodextrin, xanthan gum, and potassium chloride in
      100 ml of water maintains its consistency for at least 12 hr. The consistency
      increases after 24 hr of preparation with 1.2 g of thickener, and 48 hr with 2.4
      g of thickener. As thickened water is used for treatment of patients with
      dysphagia and air way aspiration of liquids, it is important to know how long the
      preparation maintains its consistency. It is practical to prepare the thickened
      water only once a day for patients use. Change in consistency with time may cause
      ingestion problems and does not agree with the prescription given by the group of
      professionals who is in charge to treat the patient. Deficiency in water
      ingestion causes dehydration and its consequences.

PMID- 28452159
TI  - Look behind the eyes - vasopressin rules the day.

PMID- 28452160
TI  - MicroRNA regulation of immune events at conception.
AB  - The reproductive tract environment at conception programs the developmental
      trajectory of the embryo, sets the course of pregnancy, and impacts offspring
      phenotype and health. Despite the fundamental importance of this stage of
      reproduction, the rate-limiting regulatory mechanisms operating locally to
      control fertility and fecundity are incompletely understood. Emerging studies
      highlight roles for microRNAs (miRNAs) in regulating reproductive and
      developmental processes and in modulating the quality and strength of the female
      immune response. Since endometrial receptivity and robust placentation require
      specific adaptation of the immune response, we hypothesize that miRNAs
      participate in establishing pregnancy through effects on key gene networks in
      immune cells. Our recent studies investigated miRNAs that are induced in the peri
      conception environment, focusing on miRNAs that have immune-regulatory roles
      particularly miR-223, miR-155, and miR-146a. Genetic mouse models deficient in
      individual miRNAs are proving informative in defining roles for these miRNAs in
      the generation and stabilization of regulatory T cells (Treg cells) that confer
      adaptive immune tolerance. Overlapping and redundant functions between miRNAs
      that target multiple genes, combined with multiple miRNAs targeting individual
      genes, indicate complex and sensitive regulatory networks. Although to date most
      data on miRNA regulation of reproductive events are from mice, conserved
      functions of miRNAs across species imply similar biological pathways operate in
      all mammals. Understanding the regulation and roles of miRNAs in the peri
      conception immune response will advance our knowledge of how environmental
      determinants act at conception, and could have practical applications for animal
      breeding as well as human fertility.

PMID- 28452161
TI  - Perinatal outcome and placental apoptosis in patients with late-onset pre
      eclampsia and abnormal uterine artery Doppler at diagnosis.
AB  - OBJECTIVE: To determine the rate of placental apoptosis and adverse perinatal
      outcome in patients with late-onset pre-eclampsia (PE) and abnormal uterine
      artery (UtA) Doppler at diagnosis. METHODS: This was a prospective cohort study
      of women with singleton pregnancy diagnosed with late PE, performed between
      August 2011 and January 2014 at the Maternal-Fetal Medicine Unit of Hospital
      Carlos Van Buren. Patients were stratified according to UtA Doppler status at
      diagnosis (pulsatility index (PI) <= or > 95th percentile). Logistic regression
      analysis was performed to identify associations between abnormal UtA Doppler and
      adverse maternal and perinatal outcomes. In a subset of this cohort for whom
      placental samples were available, immunohistochemical analysis of the placenta
      was performed to identify the rate of apoptosis and its association with UtA
      Doppler by comparing samples from those with normal and those with abnormal UtA
      Doppler and normotensive controls. Non-parametric linear trend analysis was
      performed for assessment of the apoptotic index. RESULTS: Eighty-six patients
      were included in the final analysis. Of these, UtA-PI was above the 95th
      percentile in 33 (38.4%) patients. Gestational age at diagnosis and delivery were
      significantly lower in this group compared with patients with normal UtA Doppler.
      Abnormal UtA Doppler was associated with increased risk of severe PE (odds ratio
      (OR) = 7.5; 95% CI, 2.76-20.46; P < 0.001), late preterm delivery (OR = 13.7; 95%
      CI, 4.53-41.46; P < 0.001), small-for-gestational age at birth (OR = 12.3; 95%
      CI, 3.17-47.57; P < 0.001) and admission to the neonatal intensive care unit (OR
      = 12.8; 95% CI, 2.61-62.36; P = 0.002). Moreover, UtA Z-score demonstrated a
      significant inverse correlation with birth-weight Z-score (r = -0.34; P =
      0.0013). Mean placental apoptotic index demonstrated an ascending linear trend
      according to UtA Doppler status (P = 0.04). CONCLUSIONS: In patients with late
      PE, UtA Doppler was useful for clinical classification and as an indicator of
      placental histological findings. Correlation between UtA Doppler and the
      apoptotic index provides new evidence of a subgroup of late PE with a placental
      origin. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 28452162
TI  - Bridging international relations and disaster studies: the case of disaster
      conflict scholarship.
AB  - International relations and disaster studies have much to gain by thinking
      critically about their respective theoretical and epistemological assumptions.
      Yet, few studies to date have sought to assess the potential value of linking
      these two disciplines. This paper begins to address this shortfall by examining
      the relationship between disasters and conflict as a research sphere that
      intersects international relations and disaster studies. Through an analysis of
      whether or not disasters contribute to intra-national and international conflict,
      this paper not only provides a review of the state of the art, but also serves to
      invite scholars to reflect on related concepts from other fields to strengthen
      their own approaches to the study of disasters in an international setting. An
      evaluation of the conceptual and theoretical contributions of each subject area
      provides useful heuristics for the development of disaster-conflict scholarship
      and encourages alternative modes of knowledge production through
      interdisciplinarity.

PMID- 28452163
TI  - 3D-Printed Transparent Glass.
AB  - Silica inks are developed, which may be 3D printed and thermally processed to
      produce optically transparent glass structures with sub-millimeter features in
      forms ranging from scaffolds to monoliths. The inks are composed of silica powder
      suspended in a liquid and are printed using direct ink writing. The printed
      structures are then dried and sintered at temperatures well below the silica
      melting point to form amorphous, solid, transparent glass structures. This
      technique enables the mold-free formation of transparent glass structures
      previously inaccessible using conventional glass fabrication processes.

PMID- 28452164
TI  - Colour polymorphism is associated with lower extinction risk in birds.
AB  - Colour polymorphisms have played a major role in enhancing current understanding
      of how selection and demography can impact phenotypes. Because different morphs
      often display alternative strategies and exploit alternative ecological niches,
      colour polymorphism can be expected to promote adaptability to environmental
      changes. However, whether and how it could influence populations' and species'
      response to global changes remains debated. To address this question, we built an
      up-to-date and complete database on avian colour polymorphism based on the
      examination of available data from all 10,394 extant bird species. We
      distinguished between true polymorphism (where different genetically determined
      morphs co-occur in sympatry within the same population) and geographic variation
      (parapatric or allopatric colour variation), because these two patterns of
      variation are expected to have different consequences on populations'
      persistence. Using the IUCN red list, we then showed that polymorphic bird
      species are at lesser risk of extinction than nonpolymorphic ones, after
      controlling for a range of factors such as geographic range size, habitat
      breadth, life history, and phylogeny. This appears consistent with the idea that
      high genetic diversity and/or the existence of alternative strategies in
      polymorphic species promotes the ability to adaptively respond to changing
      environmental conditions. In contrast, polymorphic species were not less
      vulnerable than nonpolymorphic ones to specific drivers of extinction such as
      habitat alteration, direct exploitation, climate change, and invasive species.
      Thus, our results suggest that colour polymorphism acts as a buffer against
      environmental changes, although further studies are now needed to understand the
      underlying mechanisms. Developing accurate quantitative indices of sensitivity to
      specific threats is likely a key step towards a better understanding of species
      response to environmental changes.

PMID- 28452165
TI  - Cutaneous Toxicities From Transplantation-Related Medications.
AB  - Despite the abundance of information on cutaneous malignancies associated with
      solid organ transplantation in the transplant literature, there is limited
      information regarding nonmalignant skin changes after transplantation. There are
      numerous skin toxicities secondary to immunosuppressive and other transplant
      related medications that can vary in presentation, severity, and prognosis. To
      limit associated morbidity and mortality, solid organ transplant recipient care
      providers should effectively identify and manage cutaneous manifestations
      secondary to drug toxicity. Toxicities from the following transplant-related
      medications will be discussed: antithymocyte globulins, systemic steroids,
      cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mammalian target
      of rapamycin inhibitors sirolimus and everolimus, basiliximab and daclizumab,
      belatacept, and voriconazole.

PMID- 28452166
TI  - Dorsal scapular artery as a recipient vessel in the vessel-depleted neck during
      free tissue transfer in head and neck reconstruction.
AB  - BACKGROUND: The vessel-depleted neck poses a unique challenge to the
      microvascular surgeon. Using 3D modeling and cadaveric dissection, we describe
      the approach and advantages of a known but less frequently used recipient vessel,
      the dorsal scapular artery, during free tissue transfer. METHODS: Three patients
      with vessel-depleted necks required reconstruction with free tissue transfer. The
      dorsal scapular artery was used as a recipient vessel. Three-dimensional anatomic
      models were created and cadaveric dissections were performed to characterize the
      anatomy. RESULTS: The dorsal scapular artery was successfully used in 3 patients
      as the recipient pedicle for free tissue transfer. The vessel was identified deep
      in the posterior triangle after emerging through the brachial plexus. In all
      cases, the artery was in a previously undissected field, and had a large caliber
      and favorable geometry for microvascular anastomosis. CONCLUSION: The dorsal
      scapular artery is a viable recipient vessel during head and neck reconstruction
      in the vessel-depleted neck.

PMID- 28452167
TI  - New Eudesmane Sesquiterpenoids from Salvia plebeia R. Br.
AB  - Three new sesquiterpenoids, salplebeones A - C (1 - 3), were isolated from the
      ethanol-soluble extract of the aerial part of Salvia plebeia R. Br. Their
      structures were established by detailed analysis of NMR and MS spectra.
      Salplebeone A was an eudesmane lactone, while salplebeones B and C were rare
      eudesmane sesquiterpenoids, containing 12,8-lactam groups. Antiproliferative
      activities of salplebeones A - C to myeloid leukemia cell lines were evaluated.

PMID- 28452168
TI  - Centering Single Cells in Microgels via Delayed Crosslinking Supports Long-Term
      3D Culture by Preventing Cell Escape.
AB  - Single-cell-laden microgels support physiological 3D culture conditions while
      enabling straightforward handling and high-resolution readouts of individual
      cells. However, their widespread adoption for long-term cultures is limited by
      cell escape. In this work, it is demonstrated that cell escape is predisposed to
      off-center encapsulated cells. High-speed microscopy reveals that cells are
      positioned at the microgel precursor droplets' oil/water interface within
      milliseconds after droplet formation. In conventional microencapsulation
      strategies, the droplets are typically gelled immediately after emulsification,
      which traps cells in this off-center position. By delaying crosslinking, driving
      cells toward the centers of microgels is succeeded. The centering of cells in
      enzymatically crosslinked microgels prevents their escape during at least 28 d.
      It thereby uniquely enables the long-term culture of individual cells within <5
      um-thick 3D uniform hydrogel coatings. Single cell analysis of mesenchymal stem
      cells in enzymatically crosslinked microgels reveals unprecedented high cell
      viability (>90%), maintained metabolic activity (>70%), and multilineage
      differentiation capacity (>60%) over a period of 28 d. The facile nature of this
      microfluidic cell-centering method enables its straightforward integration into
      many microencapsulation strategies and significantly enhances control,
      reproducibility, and reliability of 3D single cell cultures.

PMID- 28452169
TI  - Melanoma patient response to nivolumab treatment for metastatic lung lesions:
      Multi-OMICS analysis in Project HOPE.
AB  - A 70-year-old woman was diagnosed with a malignant melanoma of the occipital skin
      which was resected; however, multiple lung metastases were detected. Nivolumab
      therapy was initiated and partial response was obtained. However, the patient was
      diagnosed with grade 2 interstitial pneumonitis. Prednisolone administration was
      initiated and the interstitial pneumonitis shadow disappeared. However, then a
      right rib metastasis was noticed and given radiation therapy. After progressive
      disease was obtained, the metastatic lesion was resected, and no relapse occurred
      until skeletal muscle metastasis was found. According to whole-exome sequencing
      and gene expression profiling, the rib and skeletal muscle metastatic lesions
      showed an upregulated expression of programmed death-ligand 1 mRNA and a high
      single-nucleotide variant (SNV) number. The current melanoma case is
      representative of a patient who responded to nivolumab therapy, and showed
      typical immunological markers for responders such as high PD-L1 expression and
      high SNV.

PMID- 28452170
TI  - Trends in the surgical management of stage 1 renal cell carcinoma: findings from
      a population-based study.
AB  - OBJECTIVES: To determine whether the use of nephron-sparing surgery (NSS) for
      treatment of stage 1 renal cell carcinoma (RCC) changed between 2009 and the end
      of 2013 in Australia. PATIENTS AND METHODS: All adult cases of RCC diagnosed in
      2009, 2012 and 2013 were identified through the population-based Victorian Cancer
      Registry. For each identified patient, trained data-abstractors attended treating
      hospitals or clinician rooms to extract tumour and treatment data through medical
      record review. Multivariable logistic regression analyses were carried out to
      examine the significance of change in use of NSS over time, after adjusting for
      potential confounders. RESULTS: A total of 1 836 patients with RCC were
      identified. Of these, the proportion of cases with stage 1 tumours was 64% in
      2009, 66% in 2012 and 69% in 2013. For T1a tumours, the proportion of patients
      residing in metropolitan areas receiving NSS increased from 43% in 2009 to 58% in
      2012 (P < 0.05), and 69% in 2013 (P < 0.05). For patients residing in non
      metropolitan areas, the proportion receiving NSS increased from 27% in 2009 to
      49% in 2012, and 61% in 2013 (P < 0.01). Univariable logistic regression showed
      patients with moderate (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35
      0.94) or severe comorbidities (OR 0.58, 95% CI 0.33-0.99), residing in non
      metropolitan areas (OR 0.65, 95% CI 0.47-0.90), were less likely to be treated by
      NSS, while those attending high-volume hospitals (>=30 cases/year: OR 1.79, 95%
      CI 1.21-2.65) and those with higher socio-economic status (OR 1.45, 95% CI 1.02
      2.07) were more likely to be treated by NSS. In multivariable analyses, patients
      with T1a tumours in 2012 (OR 2.00, 95% CI 1.34-2.97) and 2013 (OR 3.15, 95% CI
      2.13-4.68) were more likely to be treated by NSS than those in 2009. For T1b
      tumours, use of NSS increased from 8% in 2009 to 20% in 2013 (P < 0.05).
      CONCLUSION: This population-based study of the management of T1 renal tumours in
      Australia found that the use of NSS increased over the period 2009 to 2013.
      Between 2009 and 2013 clinical practice for the treatment of small renal tumours
      in Australia has increasingly conformed to international guidelines.

PMID- 28452171
TI  - Partial Reduction and Selective Transfer of Hydrogen Chloride on Catalytic Gold
      Nanoparticles.
AB  - HCl in solution accepts electron density from Au NPs and partially reduces at
      room temperature, as occurs with other simple diatomic molecules, such as O2 and
      H2 . The activation can be run catalytically in the presence of alkynes to give
      exclusively E-vinyl chlorides, after the regio- and stereoselective transfer of
      HCl. Based also on this method, vinyl chloride monomer (VCM) can be produced in a
      milder and greener way than current industrial processes.

PMID- 28452172
TI  - Effects of nanocalcium carbonate on egg production performance and plasma calcium
      of laying hens.
AB  - This experiment was conducted to evaluate the effects of nanocalcium carbonate
      (NCC) instead of calcium carbonate (CC) on egg production, egg weight, egg mass,
      FCR, blood calcium and egg quality characteristics in laying hens. A total of 120
      laying hens were used in a 10-weeks trial, from week 23 to 33 of age. Laying hens
      were randomly assigned to six treatments with four replications, five hens each.
      The experimental treatments involved replacing 50% of the CC in the diet by
      decreasing amounts of NCC and were T1 Basal diet (BD) with 8.06% CC; T2 (6.045%
      of CC as a negative control); T3 (4.03% of CC replaced by 2.015% NCC); T4 (4.03%
      of CC replaced by 1.01% NCC); T5 (4.03% of CC replaced by 0.252% NCC) and T6
      (4.03 of CC replaced with 0.126%NCC).Egg weight was unaffected by dietary
      treatments (p > .05). However, the egg production percentage and egg mass in T6
      were less than that of other treatments (p < .05). The laying hens in the control
      group had the best average feed conversion ratio (p < .05). Also, the lowest
      concentration of calcium in hens' blood was recorded for birds fed T6 (p < .05).
      The best egg shell quality (relative egg shell weight and egg shell
      weight/surface) was observed in T1 (p < .05).Collectively, our results
      demonstrated that NCC could replace CC at a lower inclusion level but extreme
      reduction of calcium concentration in diets (to 1.43% Ca in the T6 group) reduced
      production performance, egg quality characteristics, Tibia thickness and blood
      calcium of laying hens.

PMID- 28452173
TI  - Occult HIV infection in Japanese rupioid psoriasis.

PMID- 28452174
TI  - Chemical Characterization of Lodoicea maldivica Fruit.
AB  - In the present study, we report the attempt to characterize the chemical
      composition of fruit kernel of Lodoicea maldivica coco nucifera palm (commonly
      named as 'Coco de mer') by gas chromatographic method. The analysis was performed
      by HS-SPME and GC/MS techniques to determine volatile aroma, sterol, and fatty
      acid composition profiles in the internal and external pulp of two distinct
      coconuts. Although no qualitative differences in flavour composition were
      observed between the two analysed coconuts and the relative two pulp parts,
      variations in the abundance levels of the prominent compounds have been recorded.
      The averaged quantity of total phytosterols, resulting from the two analysed
      'Coco de mer' samples, was almost constant in both kernels coconut, being 24.5
      MUg/g (of dry net matter) for the external, and 26.9 MUg/g (of dry net matter)
      for the internal portion. In both coconuts, the fatty acid pattern composition
      was characterized by seven saturated acids ranged from C14:0 (myristic) to C20:0
      (arachidic) and two monounsaturated acids, the palmitoleic (C16:1, omega7) and
      the oleic (C18:1, omega9). Palmitic acid (C16:0) was the predominant one with an
      average contribution of about 49.0%, followed by pentadecanoic 16.5%, stearic
      (C18:0) 11.6%, and myristic (C14:0) 9.9% acids in all two examined kernel
      portions.

PMID- 28452176
TI  - Microbial acceleration of aerobic pyrite oxidation at circumneutral pH.
AB  - Pyrite (FeS2 ) is the most abundant sulfide mineral on Earth and represents a
      significant reservoir of reduced iron and sulfur both today and in the geologic
      past. In modern environments, oxidative transformations of pyrite and other metal
      sulfides play a key role in terrestrial element partitioning with broad impacts
      to contaminant mobility and the formation of acid mine drainage systems. Although
      the role of aerobic micro-organisms in pyrite oxidation under acidic-pH
      conditions is well known, to date there is very little known about the capacity
      for aerobic micro-organisms to oxidize pyrite at circumneutral pH. Here, we
      describe two enrichment cultures, obtained from pyrite-bearing subsurface
      sediments, that were capable of sustained cell growth linked to pyrite oxidation
      and sulfate generation at neutral pH. The cultures were dominated by two
      Rhizobiales species (Bradyrhizobium sp. and Mesorhizobium sp.) and a Ralstonia
      species. Shotgun metagenomic sequencing and genome reconstruction indicated the
      presence of Fe and S oxidation pathways in these organisms, and the presence of a
      complete Calvin-Benson-Bassham CO2 fixation system in the Bradyrhizobium sp.
      Oxidation of pyrite resulted in thin (30-50 nm) coatings of amorphous Fe(III)
      oxide on the pyrite surface, with no other secondary Fe or S phases detected by
      electron microscopy or X-ray absorption spectroscopy. Rates of microbial pyrite
      oxidation were approximately one order of magnitude higher than abiotic rates.
      These results demonstrate the ability of aerobic microbial activity to accelerate
      pyrite oxidation and expand the potential contribution of micro-organisms to
      continental sulfide mineral weathering around the time of the Great Oxidation
      Event to include neutral-pH environments. In addition, our findings have direct
      implications for the geochemistry of modern sedimentary environments, including
      stimulation of the early stages of acid mine drainage formation and mobilization
      of pyrite-associated metals.

PMID- 28452177
TI  - Investigating the Importance of the Pocket-estimation Method in Pocket-based
      Approaches: An Illustration Using Pocket-ligand Classification.
AB  - Small molecules interact with their protein target on surface cavities known as
      binding pockets. Pocket-based approaches are very useful in all of the phases of
      drug design. Their first step is estimating the binding pocket based on protein
      structure. The available pocket-estimation methods produce different pockets for
      the same target. The aim of this work is to investigate the effects of different
      pocket-estimation methods on the results of pocket-based approaches. We focused
      on the effect of three pocket-estimation methods on a pocket-ligand (PL)
      classification. This pocket-based approach is useful for understanding the
      correspondence between the pocket and ligand spaces and to develop
      pharmacological profiling models. We found pocket-estimation methods yield
      different binding pockets in terms of boundaries and properties. These
      differences are responsible for the variation in the PL classification results
      that can have an impact on the detected correspondence between pocket and ligand
      profiles. Thus, we highlighted the importance of the pocket-estimation method
      choice in pocket-based approaches.

PMID- 28452175
TI  - Delayed lower cranial neuropathy after oropharyngeal intensity-modulated
      radiotherapy: A cohort analysis and literature review.
AB  - BACKGROUND: The purpose of this study was to examine swallowing-related lower
      cranial nerve palsy (LCNP) in oropharyngeal cancer (OPC) survivors after
      intensity-modulated radiotherapy (IMRT). METHODS: Patients treated with
      definitive IMRT (66-72 Gy) were pooled from institutional trial databases.
      Prospective analyses on parent trials included videofluoroscopy, clinical LCNP
      examination, and questionnaires pre-IMRT, 6 months post-IMRT, 12 months post
      IMRT, and 24 months post-IMRT. Time-to-event and incidence of LCNP was estimated
      with competing risk methods. Literature review (1977-2015) summarized published
      LCNP outcomes. RESULTS: Three of 59 oropharyngeal cancer survivors with a minimum
      2-year follow-up developed hypoglossal palsy ipsilateral to the index tumor
      (median latency 6.7 years; range 4.6-7.6 years). At a median of 5.7 years,
      cumulative incidence of LCNP was 5%. LCNP preceded progressive dysphagia in all
      cases. Published studies found median incidence of radiation-associated LCNP was
      10.5% after NPC, but no OPC cancer-specific estimate. CONCLUSION: Although
      uncommon, the potential for late LCNP preceding swallowing deterioration
      highlights the importance of long-term functional surveillance in OPC
      survivorship.

PMID- 28452178
TI  - Desmoplastic Reaction in 3D-Pancreatic Cancer Tissues Suppresses Molecular
      Permeability.
AB  - The survival rate of pancreatic ductal adenocarcinoma is still the lowest among
      all types of cancers, primarily as a consequence of an important desmoplastic
      reaction. Although the presence of thick stromal tissues in pancreatic tumors has
      been reported, in vivo animal studies do not enable a clear understanding of the
      crosstalk between cancer cells and fibroblasts. Accordingly, this paper reports
      the design and characterization of an in vitro pancreatic cancer-stromal 3D
      tissue model, which enhances the understanding of the interactions between cancer
      cells and fibroblasts and their influence on the secretion of extracellular
      matrix (ECM). 3D-tissue models comprising fibroblasts and pancreatic cancer cells
      (MiaPaCa-2 cell line) or colon cancer cells (HT29 cell line, used as a control)
      show decreased molecular permeability with increased cancer cell ratios. The 3D
      MiaPaCa-2 tissues display an increase in the secretion of collagen as a function
      of the cancer cell ratio, whereas 3D-HT29 tissues do not show a significant
      difference. Notably, the secretion of ECM proteins from single fibroblasts in 3D
      tissue models containing 90% MiaPaCa-2 cells is ten times higher than that under
      10% cancer cell conditions. In vitro pancreatic cancer 3D-tissues will be a
      valuable tool to obtain information on the interactions between cancer and
      stromal cells.

PMID- 28452180
TI  - Layered Rare-Earth Hydroxide/Polyacrylamide Nanocomposite Hydrogels with Highly
      Tunable Photoluminescence.
AB  - Polymer nanocomposite (NC) hydrogels, with 3D networks composed of delaminated
      inorganic nanoparticles and a polymer matrix, usually display super mechanical
      toughness. However, the few types of inorganic materials and relatively scarce
      research for NC hydrogel functions seriously limit their applications. For the
      first time layered rare-earth hydroxide (LRH)/polyacrylamide NC hydrogels with
      highly tunable photoluminescence (PL) function are reported, prepared via a
      convenient and green in situ polymerization process. Interestingly, the NC
      hydrogels reveal exciting multicolored PL phenomenon (green, yellow, orange,
      reddish-orange to bluish violet), long luminescence lifetime, and relatively high
      quantum efficiency. Furthermore, the fascinating PL function is highly tunable by
      adjusting LRH constituent or its concentration, and excitation wavelength. The
      results highlight the fabrication and applications of functional polymer NC
      hydrogels with highly tunable PL function.

PMID- 28452179
TI  - The effect of an evidence-based medicine course on medical student critical
      thinking.
AB  - OBJECTIVE: Evidence-based medicine (EBM) was designed to foster student critical
      thinking (CT) while conveying knowledge to them. Chinese medical schools have
      adopted EBM to a varying degree but studies to examine its intended effect are
      few. This study evaluates the effect of an EBM course on Chinese medical student
      CT. METHODS: A total of 158 medical students at a Chinese medical school took a
      seven-category Chinese version of the critical thinking disposition inventory
      (CTDI-CV) before and after taking an EBM course. Two-tailed, paired t-test
      measured the course effect. RESULTS: Undergraduate (BS) students showed a
      significant mean difference (MD) in confidence (MD = 1.43, P = 0.025),
      inquisitiveness (MD = 1.23, P = 0.041), and overall score (MD = 3.45, P = 0.000).
      Graduate (MS) students showed a more significant mean difference in confidence
      (MD = 2.72, P = 0.006). Moreover, BS student course grade was correlated with
      truth-seeking (r = 0.214, P = 0.029) and open-mindedness (r = 0.246, P = 0.012)
      while that of MS student was correlated with systematicity (r = 0.295, P = 0.031)
      and overall score (r = 0.290, P = 0.033). CONCLUSIONS: The results indicate some
      positive effect of an EBM course on student CT due to embedded CT elements in
      delivering the content. The discrepancy between a higher admission test score and
      weaker confidence shown by MS students reveals a drawback of the test centered
      Chinese education system.

PMID- 28452181
TI  - The 1970 Bhola cyclone, nationalist politics, and the subsistence crisis contract
      in Bangladesh.
AB  - The devastating Bhola cyclone in November 1970 is credited with having triggered
      the political events that led to the division of Pakistan and the creation of
      Bangladesh in 1971. A callous response to the disaster by the Pakistani regime
      resulted in a landslide electoral victory for Bengali nationalists, followed by a
      bitter and bloody civil war. Yet, despite its political momentousness, the Bhola
      cyclone has been the subject of little political analysis. This paper examines
      the events, arguing that its extraordinary political significance put disaster
      management on the nationalist agenda; the famine of 1974 confirmed its
      centrality, producing a social contract to protect the population against
      disasters and subsistence crises on which the country's acclaimed resilience to
      the effects of climate change rests. The Bhola cyclone also drew international
      attention to this neglected, little-known region, and in general can be seen as
      foundational for the subsequent developmental achievements of Bangladesh.

PMID- 28452182
TI  - Local injection of Lenti-Olig2 at lesion site promotes functional recovery of
      spinal cord injury in rats.
AB  - AIMS: Olig2 is one of the most critical factors during CNS development, which
      belongs to b-HLH transcription factor family. Previous reports have shown that
      Olig2 regulates the remyelination processes in CNS demyelination diseases models.
      However, the role of Olig2 in contusion spinal cord injury (SCI) and the possible
      therapeutic effects remain obscure. This study aims to investigate the effects of
      overexpression Olig2 by lentivirus on adult spinal cord injury rats. METHODS:
      Lenti-Olig2 expression and control Lenti-eGFP vectors were prepared, and virus in
      a total of 5 MUL (108 TU/mL) was locally injected into the injured spinal cord
      1.5 mm rostral and caudal near the epicenter. Immunostaining, Western blot,
      electron microscopy, and CatWalk analyzes were employed to investigate the
      effects of Olig2 on spinal cord tissue repair and functional recovery. RESULTS:
      Injection of Lenti-Olig2 significantly increased the number of oligodendrocytes
      lineage cells and enhanced myelination after SCI. More importantly, the
      introduction of Olig2 greatly improved hindlimb locomotor performances. Other
      oligodendrocyte-related transcription factors, which were downregulated or
      upregulated after injury, were reversed by Olig2 induction. CONCLUSIONS: Our
      findings provided the evidence that overexpression Olig2 promotes myelination and
      locomotor recovery of contusion SCI, which gives us more understanding of Olig2
      on spinal cord injury treatment.

PMID- 28452183
TI  - Alkyne-Substituted N-Heterophenes.
AB  - The synthesis and characterization of novel S-shaped N-heterophenes is reported.
      The targets contain a central anthracene connected to two heterophenanthrene
      units. N-Heterophenes are synthesized by reacting Boldt's 1,2,6,7
      anthracenetetraone with different dialkynylated ortho-diaminobenzenes. The
      condensation yields range from 63 to 75 %; all of the N-heterophenes are stable
      and isolable.

PMID- 28452184
TI  - Prognostic survival value of retropharyngeal lymph node involvement in sinonasal
      tumors: A retrospective, descriptive, and exploratory study.
AB  - BACKGROUND: Sinonasal carcinomas are rare. The purpose of this study was for us
      to present our assessment of the effects of retropharyngeal lymph node
      involvement at diagnosis on patient outcomes. METHODS: Retropharyngeal lymph node
      involvement in 36 patients with sinonasal carcinoma was determined by radiology
      at initial presentation. Clinical outcome, in particular, overall survival (OS)
      and locoregional control, was assessed by Kaplan-Meier analysis and log-rank
      testing. RESULTS: Retropharyngeal lymph node involvement was associated with
      statistically significant decreased OS (P = .0066) in the patient collective. In
      the squamous cell carcinoma (SCC) subgroup (n = 23), decreased OS (P = .0046) and
      worse locoregional control (P = .0065) were observed. In these patients,
      decreased OS (P = .0423) and worse locoregional control (P = .0315) were also
      seen in the advanced tumor subgroup. CONCLUSION: Retropharyngeal lymph node
      involvement at diagnosis is a significant prognostic factor for decreased OS and
      locoregional control in sinonasal carcinoma.

PMID- 28452185
TI  - Computer-aided Dereplication and Structure Elucidation of Natural Products at the
      University of Reims.
AB  - Natural product chemistry began in Reims, France, in a pharmacognosy research
      laboratory whose main emphasis was the isolation and identification of bioactive
      molecules, following the guidelines of chemotaxonomy. The structure elucidation
      of new compounds of steadily increasing complexity favored the emergence of
      methodological work in nuclear magnetic resonance. As a result, our group was the
      first to report the use of proton-detected heteronuclear chemical shift
      correlation spectra for the computer-assisted structure elucidation of small
      organic molecules driven by atom proximity relationships and without relying on
      databases. The early detection of known compounds appeared as a necessity in
      order to deal more efficiently with complex plant extracts. This goal was reached
      by an original combination of mixture fractionation by centrifugal partition
      chromatography, analysis by 13 C NMR, digital data reduction and alignment,
      hierarchical data clustering, and computer database search.

PMID- 28452186
TI  - Eocene Paleoecology of Adapis parisiensis (Primate, Adapidae): From Inner Ear to
      Lifestyle.
AB  - European adapids, especially Adapis parisiensis, have been extensively studied
      over the past two centuries, essentially for taxonomic and phylogenetic purposes.
      Analyses of dental, cranial, and postcranial morphology have led to various
      hypotheses about the diet, locomotion, and lifestyle of this fossil primate
      species. As the morphology of Adapis parisiensis is not directly comparable to
      any extant species, some interpretations are still debated. The inner ear is
      crucial to several functional parameters, such as auditory acuity, balance,
      agility, orientation, and head motion speed during locomotion. We examined the
      inner ear morphology of Adapis parisiensis in order to make some functional
      inferences, using MUCT techniques to access the internal morphology without
      damaging the fossil specimens. We analyzed the length and shape of the cochlea,
      the size of the oval window, and the size and orientation of the semicircular
      canals of seven Adapis parisiensis crania. Results indicate that the species was
      more sensitive to high frequencies than low frequencies. Results for locomotion
      style are different, depending on the method used. Results about the coefficient
      of agility are in good agreement with previous studies, proposing a slow/medium
      slow locomotion for the fossil species. In contrast, angular velocity magnitude
      (AVM) results show a great range of variation in the locomotor repertory for
      Adapis parisiensis, probably indicating that the model used is not adapted to the
      study of the fossil record. A comparison to measurements of extant strepsirhines
      leads us to conclude that Adapis parisiensis was probably monogamous and
      solitary, with a small home range. Anat Rec, 300:1576-1588, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 28452187
TI  - N-acetylcysteine versus ascorbic acid or N-acetylcysteine plus ascorbic acid in
      preventing contrast-induced nephropathy: A meta-analysis.
AB  - AIM: The purpose of the present study was to evaluate the efficacy of N
      acetylcysteine (NAC) versus ascorbic acid (VC) or NAC plus (+) VC on the
      prevention of contrast-induced nephropathy (CIN) in patients undergoing contrast
      administration. METHODS: We searched databases including Medline, Embase and
      Cochrane Library up to Feb 22 (th), 2017. Pooled risk ratios (RRs) or weighted
      mean difference (WMD) with their 95% confidence intervals (CIs) were calculated
      using fixed-effects model or random-effects model when appropriate. All analyses
      were performed using the Review Manager 5.2. RESULTS: A totalof six randomized
      controlled trials including 919 patients (478 cases received NAC administration
      and 441 cases received VC or NAC + VC administration) were considered in the meta
      analysis. Results showed that there was no significant difference in preventing
      CIN between NAC and NAC + VC administration as well as between NAC and VC
      administration. In addition, significant difference was found in serum creatinine
      level between NAC and VC or NAC + VC administration (WMD = -0.31, 95% CI: -0.48
      to -0.14, P = 0.0003) as well as NAC and VC administration (WMD = -0.05, 95% CI: 
      0.08 to -0.02, P = 0.002). Besides, NAC and NAC + VC administration also has
      significant difference (WMD = -0.72, 95% CI: -1.33 to -0.11, P = 0.02).
      CONCLUSION: In conclusion, the prevention effect of NAC administration and VC or
      NAC + VC administration on CIN was similar in patients undergoing contrast
      administration. But NAC administration was associated with a significantly lower
      serum creatinine levels compared to VC and NAC + VC administration.

PMID- 28452188
TI  - Effects of electrical stimulation on cell proliferation and apoptosis.
AB  - The application of exogenous electrical stimulation (ES) to cells in order to
      manipulate cell apoptosis and proliferation has been widely investigated as a
      possible method of treatment in a number of diseases. Alteration of the
      transmembrane potential of cells via ES can affect various intracellular
      signaling pathways which are involved in the regulation of cellular function.
      Controversially, several types of ES have proved to be effective in both
      inhibiting or inducing apoptosis, as well as increasing proliferation. However,
      the mechanisms through which ES achieves this remain fairly unclear. The aim of
      this review was to comprehensively summarize current findings from in vitro and
      in vivo studies on the effects of different types of ES on cell apoptosis and
      proliferation, highlighting the possible mechanisms through which ES induced
      these effects and define the optimum parameters at which ES can be used. Through
      this we hope to provide a greater insight into how future studies can most
      effectively use ES at the clinical trial stage.

PMID- 28452189
TI  - QT prolongation by dexamphetamine: Does experience matter?
AB  - INTRODUCTION: Case reports of life-threatening cardiac arrhythmias and sudden
      cardiac arrest (SCA) among amphetamine users have raised serious concerns about
      the cardiac safety of this class of drugs. This is important in light of the high
      prevalence of dexamphetamine (dAMPH) prescription for attention
      deficit/hyperactivity disorder (ADHD), and its rising use as a recreational drug.
      The objective was to investigate electrocardiogram (ECG) parameters upon
      intravenous administration of a single dAMPH dose in habitual recreational dAMPH
      users (users) and healthy gender/age/ intelligence-quotient-matched controls (non
      users). METHODS AND RESULTS: ECG recordings were made in 18 users and 18 non
      users during administration of dAMPH (0.3 mg/kg body weight). Baseline ECG was
      normal in both groups. dAMPH elicited increased heart rate and corrected QT time
      (QTc) prolongation in both groups (all P < 0.001, QTc = 502 in one individual).
      QTc prolongation was attenuated in users compared to non-users, exhibiting a
      significant interaction effect (P = 0.04). CONCLUSION: SCA associated with
      amphetamine use may be related to its QTc prolonging effects, particularly during
      first-time use. These observations may provide a rationale for conducting ECG
      analysis immediately after the first-time use of amphetamines, as this could
      potentially unmask vulnerable individuals.

PMID- 28452190
TI  - Practical Synthesis of both Enantiomeric Amino Acid, Mannich, and Aldol
      Derivatives by Asymmetric Organocatalysis.
AB  - In this account, we describe our recent developments in organocatalyzed
      asymmetric methodologies for the practical synthesis of both enantiomers. The
      synthesis of both enantiomeric products by using both enantiomeric catalysts is
      the most traditional way. In addition, use of two pseudoenantiomeric catalysts
      provides a more practical approach for the synthesis of both enantiomeric
      products. Even more efficient is the use of a single enantiomeric catalyst in the
      presence or absence of certain additives for obtaining both enantiomeric
      products. These three different strategies are illustrated by using certain
      organocatalyzed asymmetric approaches.

PMID- 28452192
TI  - Contribution to the discussion of '"A critical evaluation of the current p-value
      controversy"'.
AB  - I pick up a very few points of minor disagreement with Stefan Wellek's
      comprehensive review of P-values in this journal. I conclude that P-values have a
      limited function in statistical inference but can nevertheless have their uses.

PMID- 28452191
TI  - Significance of perineural invasion in locally advanced bucco alveolar complex
      carcinomas treated with surgery and postoperative radiation +/- concurrent
      chemotherapy.
AB  - BACKGROUND: The purpose of this study was to evaluate prognostic factors,
      locoregional control, and survival in locally advanced bucco-alveolar complex
      cancers. METHODS: A retrospective review of 83 patients treated between January
      2009 and December 2012 with bucco-alveolar complex cancers was conducted. All
      patients had surgery and adjuvant radiotherapy with intensity-modulated
      radiotherapy (IMRT) with/without concurrent chemotherapy. Survival analysis was
      performed using Kaplan-Meier and multivariable Cox regression model. RESULTS: On
      univariate and multivariate analysis, perineural invasion (PNI) was found to be
      an independent adverse risk factor. Patients with PNI-positive disease had
      significantly worse 2-year disease-free survival (DFS), locoregional failure free
      survival, and overall survival (OS) as compared to patients with PNI-negative
      disease (P < 0. 001, 0.001 and < 0. 001) respectively. CONCLUSION: Compared with
      patients with PNI-negative disease, patients with PNI-positive disease had much
      worse outcome despite aggressive adjuvant treatment. It warrants escalation of
      therapy and modification in radiation portals to cover neural pathways in
      patients with PNI-positive disease.

PMID- 28452193
TI  - Effects of placebos without deception compared with no treatment: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: To investigate the clinical efficacy of open-label placebos compared
      with no treatment in a systematic review and meta-analysis. METHODS: We searched
      the Cochrane Injuries Group's Specialised Register, The Cochrane Central Register
      of Controlled Trials (CENTRAL), Ovid MEDLINE(R) In-Process & Other Non-Indexed
      Citations (OvidSP), EMBASE (OvidSP), and clinical trials registers and screened
      reference lists. The search was run on 27th April 2015. We included all
      randomized controlled trials of any medical condition with open-label placebo and
      no-treatment groups. Authors independently assessed records and extracted data.
      We excluded nonrandomized trials and nonclinical studies. Risk of bias was
      assessed using Cochrane criteria. We used random-effects model for meta-analysis.
      RESULTS: We screened 348 publications, assessed 24 articles for eligibility and
      identified five trials (260 participants) that met inclusion criteria. The
      clinical conditions were: irritable bowel syndrome, depression, allergic
      rhinitis, back pain, and attention deficit hyperactivity disorder. The risk of
      bias was moderate. We found a positive effect for nondeceptive placebos
      (standardized mean difference 0.88, 95% CI 0.62 to 1.14, P < 0.00001, I2 = 1%).
      CONCLUSIONS: Open-label placebos appear to have positive clinical effects
      compared to no treatment. Caution is warranted when interpreting these results
      due to the limited number of trials identified, lack of blinding, and the fact
      that positive messages were included alongside open-label placebos. Larger
      definitive trials are now warranted to explore the potential patient benefit of
      open-label placebos, to investigate the relative contributions of positive
      suggestions, and ethical implications.

PMID- 28452194
TI  - Proteomic profiling identifies novel circulating markers associated with
      bronchiectasis in cystic fibrosis.
AB  - PURPOSE: Evaluate bronchiectasis change over 1 year in children with cystic
      fibrosis (CF) and find blood proteins associated with bronchiectasis.
      EXPERIMENTAL DESIGN: Pilot study of CF children who had chest computed tomography
      (CT) scans and blood collected during times of clinical stability. Blood plasma
      was analyzed for 1129 proteins using SOMAmer(r), the SOMAscan proteomics
      platform. Bronchiectasis was measured on two CT scans collected 1 year apart.
      Spearman's rank estimated the correlations between outcomes. Clinical relevance
      was defined as |r| >0.40. RESULTS: There were 26 children included: mean age 11.3
      years (SD 2.4 years), mean Brody Bronchiectasis score 0.65 (SD 0.83), mean airway
      count 14.3 (SD 5.7) per CT slice. Brody bronchiectasis change over 1 year ranged
      from -1.0 to 1.9 and airway count change over one year ranged from -7.7 to 13.5
      airways per slice. Proteins related to inflammation and extracellular matrix
      degradation were associated with cross-sectional and longitudinal structural
      changes. CONCLUSIONS AND CLINICAL RELEVANCE: Imaging outcomes were more strongly
      correlated with circulating proteins than age or spirometry values. The unique
      SOMAscan proteomic platform identifies several novel proteins in blood that are
      associated with bronchiectasis and that may serve as clinically useful biomarkers
      in children with CF.

PMID- 28452196
TI  - Template- and Additive-free Electrosynthesis and Characterization of Spherical
      Gold Nanoparticles on Hydrophobic Conducting Polydimethylsiloxane.
AB  - Carbon-doped poly(dimethylsiloxane) (C-PDMS) modified with gold nanoparticles
      (AuNPs) is a highly promising material for the development of flexible lab-on
      chip biosensors. Here, we present an electrochemical method to prepare stabilizer
      free AuNPs directly on hydrophobic conducting substrates like C-PDMS without
      physical or chemical pre-treatment of the C-PDMS substrate. Using a
      potentiostatic triple pulse strategy, spherical, non-stabilized AuNPs of diameter
      76+/-5 nm could be deposited within 5 s with narrow size-dispersion on the
      hydrophobic C-PDMS substrate in the absence of any structure directing or
      stabilizing agent. The detailed investigation of the mechanism of electrochemical
      formation of gold seeds and their three-dimensional growth on the hydrophobic
      surface along with nanomechanical atomic force-scanning electrochemical
      microscopy (QNM-AFM-SECM) characterization as well as conductive AFM allowed
      developing this fast electrochemical strategy with control in the desired size
      and size-dispersion of AuNPs. A detailed electrochemical investigation using
      cyclic voltammetry, anodic differential pulse voltammetry, and electrochemical
      impedance spectroscopy was conducted to characterize the electrochemical behavior
      of uncapped AuNPs deposited on C-PDMS. The Fc+ (MeOH)2 /Fc(MeOH)2 redox reaction
      at AuNPs-C-PDMS showed an improved charge transfer coefficient and heterogeneous
      charge transfer rate constant compared to the bare C-PDMS substrate.

PMID- 28452197
TI  - A comparison of UVb compact lamps in enabling cutaneous vitamin D synthesis in
      growing bearded dragons.
AB  - The effect of exposure to different UVb compact lamps on the vitamin D status of
      growing bearded dragons (Pogona vitticeps) was studied. Forty-two newly hatched
      bearded dragons (<24 h old) were allocated to six treatment groups (n = 7 per
      group). Five groups were exposed to different UVb compact lamps for two hours per
      day, with a control group not exposed to UVb radiation. At 120 days of age, blood
      samples were obtained and concentrations of 25(OH)D3 , Ca, P and uric acid were
      determined. In addition, plasma 25(OH)D3 concentration was determined in free
      living adult bearded dragons to provide a reference level. Only one treatment
      resulted in elevated levels of 25(OH)D3 compared to the control group (41.0 +/-
      12.85 vs. 2.0 +/- 0.0 nmol/L). All UVb-exposed groups had low 25(OH)D3 plasma
      levels compared to earlier studies on captive bearded dragons as well as in
      comparison with the free-living adult bearded dragons (409 +/- 56 nmol/L).
      Spectral analysis indicated that all treatment lamps emitted UVb wavelengths
      effective for some cutaneous vitamin D synthesis. None of these lamps, under this
      regime, appeared to have provided a sufficient UVb dose to enable synthesis of
      plasma 25(OH)D3 levels similar to those of free-living bearded dragons in their
      native habitat.

PMID- 28452195
TI  - Serelaxin in addition to standard therapy in acute heart failure: rationale and
      design of the RELAX-AHF-2 study.
AB  - Patients admitted for acute heart failure (AHF) experience high rates of in
      hospital and post-discharge morbidity and mortality despite current therapies.
      Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end
      organ protective effects believed to play a central role in the cardiovascular
      and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial,
      serelaxin met its primary endpoint of improving dyspnoea through day 5 in
      patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening
      heart failure (WHF) by 47% through day 5 and both all-cause and cardiovascular
      mortality by 37% through day 180. RELAX-AHF-2 ( ClinicalTrials.gov NCT01870778)
      is designed to confirm serelaxin's effect on these clinical outcomes. RELAX-AHF-2
      is a multicentre, randomized, double-blind, placebo-controlled, event-driven,
      phase 3 trial enrolling ~6800 patients hospitalized for AHF with dyspnoea,
      congestion on chest radiograph, increased natriuretic peptide levels, mild-to
      moderate renal insufficiency, and systolic blood pressure >=125 mmHg. Patients
      are randomized within 16 h of presentation to 48 h intravenous infusions of
      serelaxin (30 ug/kg/day) or placebo, both in addition to standard of care
      treatments. The primary objectives are to demonstrate that serelaxin is superior
      to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of
      WHF through day 5. Key secondary endpoints include 180 day all-cause mortality,
      composite of 180 day combined cardiovascular mortality or heart failure/renal
      failure rehospitalization, and in-hospital length of stay during index AHF. The
      results from RELAX-AHF-2 will provide data on the potential beneficial effect of
      serelaxin on cardiovascular mortality and WHF in selected patients with AHF.

PMID- 28452198
TI  - Mechanistic Insights into Palladium-Catalyzed Silylation of Aryl Iodides with
      Hydrosilanes through a DFT Study.
AB  - The catalytic cycles of palladium-catalyzed silylation of aryl iodides, which are
      initiated by oxidative addition of hydrosilane or aryl iodide through three
      different mechanisms characterized by intermediates R3 Si-PdII -H (Cycle A), Ar
      PdII -I (Cycle B), and PdIV (Cycle C), have been explored in detail by hybrid
      DFT. Calculations suggest that the chemical selectivity and reactivity of the
      reaction depend on the ligation state of the catalyst and specific reaction
      conditions, including feeding order of substrates and the presence of base. For
      less bulky biligated catalyst, Cycle C is energetically favored over Cycle A,
      through which the silylation process is slightly favored over the reduction
      process. Interestingly, for bulky monoligated catalyst, Cycle B is energetically
      more favored over generally accepted Cycle A, in which the silylation channel is
      slightly disfavored in comparison to that of the reduction channel. Moreover, the
      inclusion of base in this channel allows the silylated product become dominant.
      These findings offer a good explanation for the complex experimental
      observations. Designing a reaction process that allows the oxidative addition of
      palladium(0) complex to aryl iodide to occur prior to that with hydrosilane is
      thus suggested to improve the reactivity and chemoselectivity for the silylated
      product by encouraging the catalytic cycle to proceed through Cycles B
      (monoligated Pd0 catalyst) or C (biligated Pd0 catalyst), instead of Cycle A.

PMID- 28452199
TI  - Postoperative radiotherapy for patients with oral squamous cell carcinoma with
      intermediate risk of recurrence: A case match study.
AB  - BACKGROUND: The purpose of this study was to determine the effect of
      postoperative radiotherapy (PORT) on recurrence and survival in patients with
      oral squamous cell carcinoma (OSCC) of intermediate recurrence risk. METHODS:
      Intermediate risk patients, defined as pT1, pT2, pN0, or pN1 with at least one
      adverse pathological feature (eg, lymphovascular/perineural invasion), were
      identified from the head and neck databases of the Liverpool Head and Neck Cancer
      Unit and the Sydney Head and Neck Cancer Institute. Patients who received surgery
      and PORT were case matched with patients treated by surgery alone based on pN,
      pT, margins, and pathological features. RESULTS: Ninety patients were matched
      into 45 pairs. There was significant improvement (P = .039) in locoregional
      control with PORT (84%) compared with surgery alone (60%), which was concentrated
      in the pN1 subgroup (P = .036), but not the pN0 subgroup (P = .331). CONCLUSION:
      PORT significantly improves locoregional control for intermediate risk OSCC.

PMID- 28452200
TI  - Introduction to Volume 9, Issue 2 of topiCS.

PMID- 28452201
TI  - Six Suggestions for Research on Games in Cognitive Science.
AB  - Games are more varied and occupy more of daily life than ever before. At the same
      time, the tools available to study game play and players are more powerful than
      ever, especially massive data sets from online platforms and computational
      engines that can accurately evaluate human decisions. This essay offers six
      suggestions for future cognitive science research on games: (1) Don't forget
      about chess, (2) Look beyond action games and chess, (3) Use (near)-optimal play
      to understand human play and players, (4) Investigate social phenomena, (5) Raise
      the standards for studies of games as treatments, (6) Talk to real experts.

PMID- 28452202
TI  - Games for Psychological Science.
AB  - How does the cognitive system, as a whole, act to generate behaviour? A crucial
      requirement for science aimed at answering this question is that any empirical
      paradigm is developed hand in hand with robust theoretical models that explain
      the emergence of behavioural strategies. Complex games have the potential to be
      one such paradigm.

PMID- 28452203
TI  - Brachypodium distachyon as alternative model host system for the ergot fungus
      Claviceps purpurea.
AB  - To investigate its susceptibility to ergot infection, we inoculated Brachypodium
      distachyon with Claviceps purpurea and compared the infection symptoms with those
      on rye (Secale cereale). We showed that, after inoculation of Brachypodium with
      Claviceps, the same disease symptoms occurred in comparable temporal and spatial
      patterns to those on rye. The infection rate of Claviceps on this host was
      reduced compared with rye, but the disease could be surveyed by fungal genomic
      DNA quantification. Mutants of Claviceps which were virulence attenuated on rye
      were also affected on Brachypodium. We were able to show that pathogenesis
      related gene expression changed in a typical manner for biotrophic pathogen
      attack. Our results indicated that the Claviceps-Brachypodium interaction was
      dependent on salicylic acid, cytokinin and auxin. We consider Brachypodium to be
      a suitable and useful alternative host; the increased sensitivity compared with
      rye will be valuable for the identification of infection mechanisms. Future
      progess in understanding the Claviceps-plant interaction will be facilitated by
      the use of a well-characterized model host system.

PMID- 28452204
TI  - Mesenchymal Stem Cells: Time to Change the Name!
AB  - Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to
      represent a class of cells from human and mammalian bone marrow and periosteum
      that could be isolated and expanded in culture while maintaining their in vitro
      capacity to be induced to form a variety of mesodermal phenotypes and tissues.
      The in vitro capacity to form bone, cartilage, fat, etc., became an assay for
      identifying this class of multipotent cells and around which several companies
      were formed in the 1990s to medically exploit the regenerative capabilities of
      MSCs. Today, there are hundreds of clinics and hundreds of clinical trials using
      human MSCs with very few, if any, focusing on the in vitro multipotential
      capacities of these cells. Unfortunately, the fact that MSCs are called "stem
      cells" is being used to infer that patients will receive direct medical benefit,
      because they imagine that these cells will differentiate into regenerating tissue
      producing cells. Such a stem cell treatment will presumably cure the patient of
      their medically relevant difficulties ranging from osteoarthritic (bone-on-bone)
      knees to various neurological maladies including dementia. I now urge that we
      change the name of MSCs to Medicinal Signaling Cells to more accurately reflect
      the fact that these cells home in on sites of injury or disease and secrete
      bioactive factors that are immunomodulatory and trophic (regenerative) meaning
      that these cells make therapeutic drugs in situ that are medicinal. It is,
      indeed, the patient's own site-specific and tissue-specific resident stem cells
      that construct the new tissue as stimulated by the bioactive factors secreted by
      the exogenously supplied MSCs. Stem Cells Translational Medicine 2017;6:1445
      1451.

PMID- 28452205
TI  - Promoting innovation and access to quality, safe, efficacious, and affordable
      medicines for children: A China approach on the 69th World Health Assembly.
AB  - This study is to provide reference for the proper understanding of the content of
      "Promoting Innovation and Access to Quality, Safe, Efficacious, and Affordable
      Medicines for Children" resolution of 69th World Health Assembly (WHA), and
      facilitate the policy making and implication of the Resolution. Through
      descriptive analysis, the author introduce the proposal background and approving
      process of the resolution, and interpret the resolution content. The approval of
      "Promoting Innovation and Access to Quality, Safe, Efficacious, and Affordable
      Medicines for Children" at WHA represents China's international discourse right
      on improving the basic medical service among children, the most vulnerable
      population; highlights China's responsibility and magnitude of a great nation. It
      is an effective promotion for China's new medical reform and the implication of
      the Millennium Development Goals (MDGs), as well as a great contribution to the
      global health of children from China.

PMID- 28452206
TI  - Clinical Considerations of Silent Gastroesophageal Reflux Disease in Morbidly
      Obese Patients.

PMID- 28452207
TI  - Micronutrients Should Be Monitored in the Real Practice for Korean Inflammatory
      Bowel Disease Patients.

PMID- 28452208
TI  - Disability Index as a New Outcome Measure in Patients with Inflammatory Bowel
      Disease.

PMID- 28452209
TI  - Can Magnetic Resonance Elastography Fill a Niche in the Market for Noninvasive
      Assessment of Liver Fibrosis?

PMID- 28452211
TI  - Erratum: Pathophysiology and Management of Alcoholic Liver Disease: Update 2016.
AB  - Page 178, Fig. 3: The following note should be included as the last line of the
      figure legend: "The figure has been adapted from its original published in He S,
      et al. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty
      liver disease disrupts triglyceride hydrolysis. J Biol Chem 2010;285:6706-6715.

PMID- 28452212
TI  - The prevalence of hypertension in children with renal scars.
AB  - BACKGROUND: Hypertension (HTN) is a late outcome of congenital or acquired renal
      scar. We used ambulatory blood pressure to assess the early blood pressure
      abnormalities in children with history of urinary tract infection with various
      degrees of renal scars. METHODS: Between 2009 and 2011, 60 (45 females, 15 males)
      children aged 5-15 years and height equal or more than 120 cm with previous
      history of febrile urinary tract infection were entered into the study. All
      children went on 24-hour ambulatory blood pressure monitoring (24-H ABPM).
      Updated classification of 24-H ABPM was used to interpret the results. RESULTS:
      Masked hypertension was detected in 5% of cases, hypertension in 8.4%, and white
      coat hypertension in 11.7%. Pre-hypertension was seen in 23.3% of children. There
      was significant correlation between abnormal blood pressure and the severity of
      renal parenchymal scar (r=0.39, P value=0.004), vesicoureteral reflux (r= 0.34, P
      value=0.009), microalbuminuria (r= 0.39, P value=0.004), and carotid intima media
      thickness (r=0.41, P value=0.006). CONCLUSIONS: This study revealed the utility
      of 24-H ABPM in early detection of hypertension and pre-hypertension in children
      with severe renal scars and past history of urinary tract infection.

PMID- 28452210
TI  - Functional Dyspepsia: Advances in Diagnosis and Therapy.
AB  - Functional dyspepsia (FD) is a common but under-recognized syndrome comprising
      bothersome recurrent postprandial fullness, early satiety, or epigastric
      pain/burning. Epidemiologically, there are two clinically distinct FD syndromes
      (although these often overlap clinically): postprandial distress syndrome (PDS;
      comprising early satiety or meal-related fullness) and epigastric pain syndrome.
      Symptoms of gastroesophageal reflux disease overlap with FD more than expected by
      chance; a subset has pathological acid reflux. The pretest probability of FD in a
      patient who presents with classical FD symptoms and no alarm features is high,
      approximately 0.7. Coexistent heartburn should not lead to the exclusion of FD as
      a diagnosis. One of the most exciting observations in FD has been the consistent
      finding of increased duodenal eosinophilia, notably in PDS. Small bowel homing T
      cells, signaling intestinal inflammation, and increased cytokines have been
      detected in the circulation, and elevated tumor necrosis factor-alpha levels have
      been significantly correlated with increased anxiety. Postinfectious
      gastroenteritis is a risk factor for FD. Therapeutic options remain limited and
      provide only symptomatic benefit in most cases. Only one therapy is known to
      change the natural history of FD-Helicobacter pylori eradication. Treatment of
      duodenal eosinophilia is under investigation.

PMID- 28452213
TI  - Oxygen Vacancies Control Transition of Resistive Switching Mode in Single-Crystal
      TiO2 Memory Device.
AB  - Epitaxial TiO2 thin films were grown by radio-frequency magnetron sputtering on
      conductive Nb-SrTiO3 substrates. X-ray photoelectron spectroscopy reveals that
      the oxygen vacancies inside the TiO2 films can be dramatically reduced by
      postannealing treatment under an oxygen atmosphere. The decreasing concentration
      of oxygen vacancies modifies the resistive switching (RS) mechanism from a
      valence change mode to a electrochemical metallization mode, resulting in a high
      switching ratio (>=105), a small electronic leakage current in the high
      resistance (>=109 Omega) state, and a highly controlled quantized conductance
      (QC) in the low-resistance state. These results allow for understanding the
      relationship between different RS mechanisms as well as the QC for multilevel
      data storage application.

PMID- 28452214
TI  - High-Resolution Bubble Printing of Quantum Dots.
AB  - Semiconductor quantum dots (QDs) feature excellent properties, such as high
      quantum efficiency, tunable emission frequency, and good fluorescence stability.
      Incorporation of QDs into new devices relies upon high-resolution and high
      throughput patterning techniques. Herein, we report a new printing technique
      known as bubble printing (BP), which exploits a light-generated microbubble at
      the interface of colloidal QD solution and a substrate to directly write QDs into
      arbitrary patterns. With the uniform plasmonic hot spot distribution for high
      bubble stability and the optimum light-scanning parameters, we have achieved full
      color QD printing with submicron resolution (650 nm), high throughput (scanning
      rate of ~10-2 m/s), and high adhesion of the QDs to the substrates. The printing
      parameters can be optimized to further control the fluorescence properties of the
      patterned QDs, such as emission wavelength and lifetime. The patterning of QDs on
      flexible substrates further demonstrates the wide applicability of this new
      technique. Thus, BP technique addresses the barrier of achieving a widely
      applicable, high-throughput and user-friendly patterning technique in the
      submicrometer regime, along with simultaneous fluorescence modification
      capability.

PMID- 28452215
TI  - Electrostatic Spray Ionization from 384-Well Microtiter Plates for Mass
      Spectrometry Analysis-Based Enzyme Assay and Drug Metabolism Screening.
AB  - We have realized the direct ionization of samples from wells of microtiter plates
      under atmospheric conditions for mass spectrometry analysis without any liquid
      delivery system or any additional interface. The microtiter plate is a
      commercially available 384-well plate without any modification, working as a
      container and an emitter for electrostatic spray ionization of analytes. The
      approach provides high throughput for the large batches of reactions and both the
      qualitative and quantitative analysis of a single compound or mixture. The limits
      of detection in small drug molecules, peptides, and proteins are similar in
      comparison with standard direct infusion electrospray ionization. The analysis
      time per well is only seconds. These analytical merits benefit many microtiter
      plate-based studies, such as combinatorial chemistry and high throughput
      screening in enzyme assay or drug metabolism. Herein, we illustrate the
      application in enzyme assay using tyrosine oxidation catalyzed by tyrosinase in
      the presence or absence of inhibitors. The potential application in drug
      development is also demonstrated with cytochrome P450-catalyzed metabolic
      reactions of two drugs in microtiter plates followed with direct ESTASI-MS/MS
      based characterization of the metabolism products.

PMID- 28452216
TI  - Applying Carbon Dots-Metal Ions Ensembles as a Multichannel Fluorescent Sensor
      Array: Detection and Discrimination of Phosphate Anions.
AB  - Fluorescent carbon dots (CDs) are attracting much attention in sensing recently
      thanks to their superior optical properties and abundant surface functional
      groups. To take further advantages of these unique features, CDs are considered
      to be possible for facilely fabricating multichannel sensor arrays. As a proof-of
      concept research, CDs-metal ions ensembles are screened and designed as a triple
      channel fluorescent sensor array in this study for the identification of various
      phosphate anions (e.g., ATP, ADP, AMP, PPi, and Pi) for the first time. Further
      studies reveal that the selected three metal ions (i.e., Ce3+, Fe3+, and Cu2+)
      could induce aggregation of the CDs, resulting in quenching of their
      fluorescence. However, disaggregation or further aggregation of the CDs-metal
      ions ensembles occurs with the addition of phosphate anions. Consequently,
      fluorescence of the CDs is recovering or further quenching. On account of various
      numbers of phosphate group and steric hindrance effects of phosphate anions,
      their affinities to the sensor array can be distinguished through fluorescence
      changes of the CDs-metal ions ensembles. By means of statistical analysis
      methods, the as-developed array is shown excellent capabilities in the detection
      and discrimination of phosphate anions. Furthermore, practicability of the sensor
      array is validated by the successful identification of phosphates in serum and
      blind samples. Compared to previous reports, the as-developed multichannel sensor
      array manifests numerous advantages, such as simple fabrication process, flexible
      adjusting detection ranges, and possible extension to other analytes having
      similar chemical structures or properties.

PMID- 28452217
TI  - Fe(II)/Au(I) Relay Catalyzed Propargylisoxazole to Pyridine Isomerization: Access
      to 6-Halonicotinates.
AB  - An efficient synthesis of methyl nicotinates/6-halonicotinates by the domino
      isomerization of 4-propargyl/(3-halopropargyl)-5-methoxyisoxazoles under
      Fe(II)/Au(I) relay catalysis was developed. It was found that FeNTf2 is an
      effective catalyst for first step of the domino isomerization, transformation of
      isoxazole to 2H-azirine, which is compatible with Ph3PAuNTf2, catalyzing the
      second step.

PMID- 28452218
TI  - Quantifying Diffuse Contamination: Method and Application to Pb in Soil.
AB  - A new method for detecting and quantifying diffuse contamination at the
      continental to regional scale is based on the analysis of cumulative distribution
      functions (CDFs). It uses cumulative probability (CP) plots for spatially
      representative data sets, preferably containing >1000 determinations. Simulations
      demonstrate how different types of contamination influence elemental CDFs of
      different sample media. It is found that diffuse contamination is characterized
      by a distinctive shift of the low-concentration end of the distribution of the
      studied element in its CP plot. Diffuse contamination can be detected and
      quantified via either (1) comparing the distribution of the contaminating element
      to that of an element with a geochemically comparable behavior but no
      contamination source (e.g., Pb vs Rb), or (2) comparing the top soil distribution
      of an element to the distribution of the same element in subsoil samples from the
      same area, taking soil forming processes into consideration. Both procedures are
      demonstrated for geochemical soil data sets from Europe, Australia, and the
      U.S.A. Several different data sets from Europe deliver comparable results at
      different scales. Diffuse Pb contamination in surface soil is estimated to be
      <0.5 mg/kg for Australia, 1-3 mg/kg for Europe, and 1-2 mg/kg, or at least <5
      mg/kg, for the U.S.A. The analysis presented here also allows recognition of
      local contamination sources and can be used to efficiently monitor diffuse
      contamination at the continental to regional scale.

PMID- 28452219
TI  - Toehold Mediated One-Step Conformation-Switchable "Signal-On" Electrochemical DNA
      Sensing Enhanced with Homogeneous Enzymatic Amplification.
AB  - The development of highly sensitive and sequence-specific electrochemical DNA (E
      DNA) sensors, featuring flexible, one-step, and "signal-on" design, is a long
      lasting goal. Here, we present a single-step, toehold-triggered structure
      switchable signaling design that is "signal-on" and compatible with homogeneous
      enzyme-assisted target recycling (EATR). In this design, a partially hybridized
      duplex is bifunctional, which consists of a signal probe having foldable hairpin
      sequence and a target recognition probe with exposed toehold domain. In the
      presence of both target and exonuclease, the toehold sequence rapidly fuels the
      strand displacement reaction, liberating the surface-confined toehold-target
      duplex into homogeneous solution for target recycling and meanwhile leaving the
      dehybridized signal probe to form a stem-loop structure for signaling. Through
      such an 1:N enzymatic catalysis, more and more unfolded probes self-hybridize to
      their original folded configuration, giving a remarkable signal gain. This enzyme
      assisted toehold E-DNA (etE-DNA) sensor achieves a satisfactory detection limit
      down to 42 fM, which is lower than that of the routine switchable E-DNA sensor by
      several orders of magnitude. In addition, the strategy shows high selectivity
      against a single-base mismatch and is capable of probing low abundant target DNA
      directly in human serum with minimal interference. By synergizing the toehold
      based high selectivity, EATR, and one-step conformation-switchable signaling,
      this functional etE-DNA sensor appears to be a promising bioassay approach for
      clinical diagnostics.

PMID- 28452220
TI  - Exposure to SVOCs from Inhaled Particles: Impact of Desorption.
AB  - Inhaled semivolatile organic compounds (SVOCs) are simultaneously present in gas
      and particle phases. Particles desorb a fraction of their SVOCs moving through
      the human respiratory tract (RT). Quantifying such desorption is challenging but
      important since gas- and particle-phase SVOCs deposit in different locations in
      the RT, encountering different cell populations with varying health consequences.
      This paper presents a mass transfer model to quantify this desorption process in
      the head, tracheobronchial, and alveolar regions of the RT. The desorption of
      SVOCs from inhaled particles can be gauged using the ratio of particle residence
      time to the time required to achieve particle/gas equilibrium. Results indicate
      that the larger this ratio is, the more likely particles desorb the SVOCs they
      carry. For particles smaller than 0.5 MUm diameter and SVOCs with a particle/gas
      partition coefficient (unitless) of 1010, accounting for desorption reduces the
      estimated particle-phase SVOC concentrations in the alveolar region by more than
      35%; the reduction is almost 700% for 0.05 MUm diameter particles. In
      hypothetical scenarios representing common indoor and outdoor situations,
      neglecting desorption significantly overestimates the concentration of ultrafine
      particle associated SVOCs in the alveolar region. This model is a preliminary
      step toward more nuanced estimates of exposure to inhaled SVOCs.

PMID- 28452221
TI  - Surface-Enhanced Raman Spectroscopy Combined with Stable Isotope Probing to
      Monitor Nitrogen Assimilation at Both Bulk and Single-Cell Level.
AB  - Microbe-mediated biogeochemical cycle of nitrogen is a critical process in the
      environment. In this study, surface-enhanced Raman spectroscopy combined with 15N
      stable isotope probing (SERS-15N SIP) was developed as a new, nondestructive, and
      robust approach to probe nitrogen assimilation by bacteria at both bulk and
      single-cell level, and from pure culture to environmental microbial community.
      Multiple distinguishable SERS band shifts were observed and displayed a linear
      relationship with 15N content, because of the substitution of "light" nitrogen by
      "heavier" 15N stable isotope. These shifts, especially in 730 cm-1 band, were
      highly distinguishable and universal in different bacteria, providing a robust
      indicator for nitrogen assimilation in bacteria. SERS-15N SIP was also
      demonstrated in important N2-fixing bacteria via 15N2 incubations. The same
      prominent shifts as that induced by 15NH4Cl were observed, indicating the
      applicability of SERS-15N SIP to different nitrogen sources. SERS-15N SIP was
      further applied to environmental microbial community via 15NH4Cl, 15NO3-, and
      15N2 incubation. Bacteria- and nitrogen source-dependent activity in nitrogen
      assimilation were revealed in environmental microbial community, pointing to the
      bacterial diversity and necessity of single-cell level investigation. Finally, by
      mixing optimized ratio of bacteria with Ag NPs, explicit single-cell SERS-15N SIP
      was obtained. The nondestructive SERS-15N SIP approach will be useful not only to
      identify active nitrogen-assimilating cells, but also enable Raman activated cell
      sorting and downstream genomic analysis, which will bring in deep insights into
      nitrogen metabolism of environmental microorganisms.

PMID- 28452223
TI  - Comparing the Electrochemical Response of Nanostructured Electrode Arrays.
AB  - The electrochemical responses from periodic 6 * 6 arrays of recessed gold
      nanorings were compared to the 6 * 6 recessed gold nanodiscs arrays. The
      nanostructured arrays were fabricated by focused ion beam milling and their
      electrochemical response from a reversible redox pair was obtained. Three
      dimensional cyclic voltammetry simulations using COMSOL were performed on 6 * 6
      periodic arrays of both recessed nanodiscs and nanorings to elucidate the
      differences in mass transport between these geometries. Specific mass transport
      properties near the electroactive surface of the electrodes were elucidated by
      analyzing the calculated concentration profiles of the redox species. Relative
      contributions from radial diffusion regimes inside the nanoholes play an
      important role on the electrochemical response of the recessed nanorings. Arrays
      of nanodiscs are common in different types of applications, particularly in
      biosensors. The results presented here suggest that the performance and
      sensitivity of electrochemical nanosensors can be simply improved by implementing
      electrodes with a geometry which offer greater current density while keeping the
      overall footprint of the sensor element constant.

PMID- 28452224
TI  - Ultrathin Multifunctional Graphene-PVDF Layers for Multidimensional Touch
      Interactivity for Flexible Displays.
AB  - This paper presents a flexible graphene/polyvinylidene difluoride (PVDF)/graphene
      sandwich for three-dimensional touch interactivity. Here, x-y plane touch is
      sensed using graphene capacitive elements, while force sensing in the z-direction
      is by a piezoelectric PVDF/graphene sandwich. By employing different frequency
      bands for the capacitive- and force-induced electrical signals, the two stimuli
      are detected simultaneously, achieving three-dimensional touch sensing. Static
      force sensing and elimination of propagated stress are achieved by augmenting the
      transient piezo output with the capacitive touch, thus overcoming the intrinsic
      inability of the piezoelectric material in detecting nontransient force signals
      and avoiding force touch mis-registration by propagated stress.

PMID- 28452222
TI  - Application of Nanosecond Laser Photolysis Protein Footprinting to Study EGFR
      Activation by EGF in Cells.
AB  - Mass spectrometry-based protein footprinting emerged as a useful technology to
      understand protein ligand interactions in vitro. We have previously demonstrated
      the application of footprinting in live E. coli cells. Here, we further optimized
      an ultrafast laser photolysis hydroxyl radical footprinting method and applied it
      to study the interaction of EGF and EGFR in live mammalian cells. This method
      used a nanosecond laser to photochemically generate a burst of hydroxyl radicals
      in situ in-cell suspension to oxidize the amino acids on the protein surface.
      Mass spectrometric analysis of the thus modified peptides was interpreted to
      probe the solvent-accessible surface areas of the protein in its native
      biological state with and without EGF activation. Our footprinting data agreed
      with the two relevant EGFR crystal structures, indicating that this in-cell laser
      photolysis footprinting technique is a valid approach to study the structural
      properties of integral membrane proteins directly in the native environment.

PMID- 28452225
TI  - Strategy for Conditional Orthogonal Sequential CuAAC Reactions Using a Protected
      Aromatic Ynamine.
AB  - A method for conditional control of orthogonal sequential Cu-catalyzed azide
      alkyne cycloaddition (CuAAC) reactions is reported. The inherent reactivity of an
      aromatic ynamine is controlled by a silyl protecting group that allows the
      selective CuAAC reaction of less reactive alkynes. Alternatively, the same
      protected ynamine undergoes selective CuAAC reaction via silyl deprotection in
      situ to give the ynamine click products. This allows complete orthogonal control
      of dialkyne systems and provides a unifying strategy for chemoselective CuAAC
      ligations in multialkyne/azide systems.

PMID- 28452226
TI  - The cost-effectiveness of blue-light therapy in the treatment of mild-to-moderate
      psoriasis.
AB  - AIM: To investigate the cost-effectiveness of blue-light therapy versus a two
      compound formulation (TCF) (Dovobet(r) gel [calcipotriol and betamethasone]) in
      mild-to-moderate psoriasis. METHODS: A Markov model was applied to describe the
      course of disease among Dutch patients with a Psoriasis Area and Severity Index
      (PASI) score <= 10 over a 52-week time horizon. Patients received either 12-week
      blue-light therapy or two 4-week treatments with TCF. Patients, experiencing no
      PASI reduction after either therapy, were assumed to receive 12-week ultraviolet
      B phototherapy. RESULTS: There was no significant difference in PASI reduction
      between two interventions (71 vs 72%). However, blue-light therapy was associated
      with a cost savings of EU?248. CONCLUSION: Treatment of mild-to-moderate chronic
      plaque psoriasis using blue-light therapy may be more cost-effective than TCF.

PMID- 28452227
TI  - Prediction of Lignin Content in Different Parts of Sugarcane Using Near-Infrared
      Spectroscopy (NIR), Ordered Predictors Selection (OPS), and Partial Least Squares
      (PLS).
AB  - The building of multivariate calibration models using near-infrared spectroscopy
      (NIR) and partial least squares (PLS) to estimate the lignin content in different
      parts of sugarcane genotypes is presented. Laboratory analyses were performed to
      determine the lignin content using the Klason method. The independent variables
      were obtained from different materials: dry bagasse, bagasse-with-juice, leaf,
      and stalk. The NIR spectra in the range of 10 000-4000 cm-1 were obtained
      directly for each material. The models were built using PLS regression, and
      different algorithms for variable selection were tested and compared: iPLS,
      biPLS, genetic algorithm (GA), and the ordered predictors selection method (OPS).
      The best models were obtained by feature selection with the OPS algorithm. The
      values of the root mean square error prediction (RMSEP), correlation of
      prediction ( RP), and ratio of performance to deviation (RPD) were, respectively,
      for dry bagasse equal to 0.85, 0.97, and 2.87; for bagasse-with-juice equal to
      0.65, 0.94, and 2.77; for leaf equal to 0.58, 0.96, and 2.56; for the middle
      stalk equal to 0.61, 0.95, and 3.24; and for the top stalk equal to 0.58, 0.96,
      and 2.34. The OPS algorithm selected fewer variables, with greater predictive
      capacity. All the models are reliable, with high accuracy for predicting lignin
      in sugarcane, and significantly reduce the time to perform the analysis, the cost
      and the chemical reagent consumption, thus optimizing the entire process. In
      general, the future application of these models will have a positive impact on
      the biofuels industry, where there is a need for rapid decision-making regarding
      clone production and genetic breeding program.

PMID- 28452228
TI  - Medical treatment or revascularisation as the best approach for spontaneous
      coronary artery dissection: A systematic review and meta-analysis.
AB  - INTRODUCTION: Patients presenting with spontaneous coronary artery dissection
      (SCAD) may receive either conservative medical management or a revascularisation
      strategy. There is still a lack of consensus with respect to the best treatment
      approach for SCAD. OBJECTIVES: We sought to determine whether outcomes differ
      between the first-line treatment approaches (conservative versus
      revascularisation) in patients with SCAD. METHODS: We searched Medline, EMBASE
      and the Cochrane Library for studies published from January 1990 to November 2016
      that compared first-line treatments for patients with SCAD. We conducted a pooled
      risk ratio meta-analysis for four main outcomes: mortality, myocardial infarction
      (MI), SCAD recurrence and target vessel revascularisation (TVR). RESULTS: We
      identified 11 non-randomised studies that included a total of 631 patients. A
      pooled meta-analysis showed no significant difference between conservative
      management and revascularisation approaches in mortality (risk difference [RD] =
      0.01; 95% confidence interval [CI] = -0.01 to 0.04; I2 = 0%; p = 1), MI (RD = 
      0.01; 95% CI = -0.04 to 0.03; I2 = 0%; p = 0.5) or SCAD recurrence (RD = -0.01;
      95% CI = -0.06 to 0.05; I2 = 0%; p = 0.74). Revascularisation as an initial first
      line approach was associated with an estimated additional risk of TVR of 6.3% (RD
      = 0.06; 95% CI = 0.01-0.11; I2 = 0%; p = 0.96). CONCLUSION: The results
      demonstrate an increased risk of TVR when revascularisation was used as the
      initial first-line treatment approach. The treatment decision must be
      individualised and be based on both clinical and angiographic factors, but
      conservative therapy should prevail in most cases.

PMID- 28452229
TI  - Book ReviewReviews.
AB  - Leonard Reinecke and Mary Beth Oliver (Eds.) The Routledge Handbook of Media Use
      and Well-Being Routledge, New York, NY, 2017, 465 pp. ISBN: 978-1-138-88658-2.

PMID- 28452230
TI  - Comparing Book- and Tablet-Based Picture Activity Schedules: Acquisition and
      Preference.
AB  - Picture activity schedules consist of a sequence of images representing the order
      of tasks for a person to complete. Although, picture activity schedules have
      traditionally been presented in a book format, recently picture activity
      schedules have been evaluated on technological devices such as an iPodTM touch.
      The present study compared the efficiency of picture activity schedule
      acquisition on book- and tablet-based modalities. In addition, participant
      preference for each modality was assessed. Three boys aged below 5 years with a
      diagnosis of autism participated. Participants were taught to follow the
      schedules using both modalities. Following mastery of each modality of picture
      activity schedule, a concurrent-chains preference assessment was conducted to
      evaluate participant preference for each modality. Differences in acquisition
      rates across the two modalities were marginal. Preference for book- or tablet
      based schedules was idiosyncratic across participants.

PMID- 28452231
TI  - Editor's Choice- Activation of the innate immune system in the pathogenesis of
      acute heart failure.

PMID- 28452232
TI  - Genetic polymorphisms of IL-23R (rs7517847) and LEP (rs7799039) among Egyptian
      patients with hepatocellular carcinoma.
AB  - BACKGROUND: Genetic polymorphisms of IL-23 R (rs7517847) and LEP (rs7799039) have
      been stated to be associated with various types of human cancers. The purpose of
      this work is to test the association of these genetic polymorphisms with
      hepatocellular carcinoma (HCC) among Egyptian patients. SUBJECTS AND METHODS:
      This study involved 150 unrelated Egyptian HCC patients in addition to 100
      healthy controls from the same locality. DNA was genotyped for these genetic
      polymorphisms using the PCR-RFLP technique. RESULTS: The frequency of the IL-23 R
      (rs7517847) G and LEP (rs7799039) G alleles were significantly higher among HCC
      patients compared to controls (p = .004 and .02). However, HCC patients with the
      IL-23 R GG and LEP GG genotypes showed no significant difference compared to
      others regarding their clinical and laboratory markers. CONCLUSIONS: IL-23 R
      (rs7517847) and LEP (rs7799039) polymorphisms were associated with an increased
      risk but not affecting the clinical presentation of HCC among Egyptian patients.

PMID- 28452233
TI  - Improving Wisely Using Physician Metrics.

PMID- 28452234
TI  - Analytically diagnosed intoxication by 2-methoxphenidine and flubromazepam
      mimicking an ischemic cerebral disease.

PMID- 28452235
TI  - Molecular characteristics, biofilm-forming abilities, and quorum sensing
      molecules in Vibrio parahaemolyticus strains isolated from marine and clinical
      environments in Korea.
AB  - Vibrio parahaemolyticus is an inhabitant of marine and estuarine environments and
      causes seafood-borne gastroenteritis in humans. In this study, an UltraFast
      LabChip Real-Time PCR assay was evaluated for rapid detection and quantification
      of pathogenic V. parahaemolyticus isolates. Escherichia coli and Vibrio harveyi
      were used as negative controls. Twenty-six tdh-positive, biofilm-producing V.
      parahaemolyticus isolates were analyzed by repetitive extragenic palindromic
      polymerase chain reaction (REP-PCR). REP-PCR analysis showed that the majority of
      the V. parahaemolyticus isolates originated from seafood and that clinical
      specimens formed two major clusters at 92.8% and 32% similarity levels. The
      presence and quantification of Autoinducer-2 was carried out using high
      performance liquid chromatography with fluorescence detection (HPLC-FLD) after
      derivatization of Autoinducer-2 with 2, 3-diaminonaphthalene. The presence of tdh
      positive V. parahaemolyticus in marine samples highlights the need for constant
      environmental monitoring to protect public health.

PMID- 28452236
TI  - Mobile access to virtual randomization for investigator-initiated trials.
AB  - Background/aims Randomization is indispensable in clinical trials in order to
      provide unbiased treatment allocation and a valid statistical inference. Improper
      handling of allocation lists can be avoided using central systems, for example,
      human-based services. However, central systems are unaffordable for investigator
      initiated trials and might be inaccessible from some places, where study subjects
      need allocations. We propose mobile access to virtual randomization, where the
      randomization lists are non-existent and the appropriate allocation is computed
      on demand. Methods The core of the system architecture is an electronic data
      capture system or a clinical trial management system, which is extended by an R
      interface connecting the R server using the Java R Interface. Mobile devices
      communicate via the representational state transfer web services. Furthermore, a
      simple web-based setup allows configuring the appropriate statistics by non
      statisticians. Our comprehensive R script supports simple randomization,
      restricted randomization using a random allocation rule, block randomization, and
      stratified randomization for un-blinded, single-blinded, and double-blinded
      trials. For each trial, the electronic data capture system or the clinical trial
      management system stores the randomization parameters and the subject
      assignments. Results Apps are provided for iOS and Android and subjects are
      randomized using smartphones. After logging onto the system, the user selects the
      trial and the subject, and the allocation number and treatment arm are displayed
      instantaneously and stored in the core system. So far, 156 subjects have been
      allocated from mobile devices serving five investigator-initiated trials.
      Conclusion Transforming pre-printed allocation lists into virtual ones ensures
      the correct conduct of trials and guarantees a strictly sequential processing in
      all trial sites. Covering 88% of all randomization models that are used in recent
      trials, virtual randomization becomes available for investigator-initiated trials
      and potentially for large multi-center trials.

PMID- 28452237
TI  - GLP-1 and GIP Levels in Patients With Hyperthyroidism: The Effect of Antithyroid
      Treatment.
AB  - BACKGROUND: Incretin hormones (glucagon-like peptide-1 [GLP-1] and gastric
      inhibitory polypeptide [GIP]) may play a role in the development of glucose
      intolerance and hyperglycemia in patients with hyperthyroidism. OBJECTIVE: We
      aimed to assess both incretin levels and treatment-induced changes in incretin
      levels in those with hyperthyroidism. METHODS: A total of 24 subjects (12 with
      hyperthyroidism and 12 healthy) were enrolled in the study. Oral glucose
      tolerance test was performed and serum glucose, insulin GLP1, and GIP levels were
      evaluated at 0 (baseline), 30, 60, 90, and 120 minutes using ELISA. Measurements
      were repeated after euthyroidism was reached in subjects with hyperthyroidism.
      RESULTS: The baseline glucose level was higher in those with hyperthyroidism
      compared with controls ( P = 0.03). GLP-1 and GIP responses to oral glucose load
      did not differ significantly between those with hyperthyroidism and controls.
      Peak GLP-1 and GIP levels were reached in both groups at 60 and 90 minutes,
      respectively. Areas under the curve (AUCs) for GLP1 and GIP were similar in those
      with hyperthyroidism and controls. Although GLP-1 and GIP levels did not change
      before and after antithyroid treatment in subjects with hyperthyroidism, time to
      peak GLP-1 and GIP levels were reached at 30 minutes after euthyroid state was
      achieved. Reversal of hyperthyroid to euthyroid status did not induce significant
      changes in AUCs for incretins. CONCLUSION: The findings of the present study
      suggest that the total incretin response to oral glucose load is preserved in
      patients with hypertyhroidism, but peak incretin responses may change after
      achieving euthyroid state.

PMID- 28452239
TI  - Correction to: Faster acquisition of laparoscopic skills in virtual reality with
      haptic feedback and 3D vision.

PMID- 28452238
TI  - Identification of novel genetic variants in the mutational hotspot region 14 kb
      upstream of the LCT gene in a Mexican population.
AB  - Several polymorphic loci linked to lactase persistence (LP) have been described,
      all located in a small mutational hotspot region far upstream (~14 kb) of the
      lactase (LCT) gene. One is typically found in Europeans, LCT -13910C > T, several
      others are found in East Africans and Arabs, e.g. LCT -13907C > G and LCT -13915T
      > G. The possibility of similar loci, specific to populations in South and
      Central America, has not received much attention so far. To identify possible
      novel polymorphisms in the mutational hotspot region, we sampled 158 subjects
      from a rural area in South-Central Mexico. DNA was isolated from serum, and
      Sanger sequencing of a 501 bp region spanning the LCT -13910C > T hotspot was
      successfully performed in 150 samples. The frequency of the European-type LCT 
      13910 T-allele was q = 0.202, and 35% of the population was thus lactase
      persistent (CT or TT). Sixteen novel genetic variants were found amongst 11 of
      the subjects, all were heterozygotes: seven of the subjects were also carriers of
      at least one LCT -13910 T-allele. Thus, the mutational hotspot region is also a
      hotspot in the rural Mexican population: 11/150 subjects carried a total of 16
      previously unknown private mutations but no novel polymorphism was found. The
      relationship between such novel genetic variants in Mexicans and lactase
      persistence is worthy of more investigation.

PMID- 28452240
TI  - Efficacy comparison of oral rosuvastatin versus oral progesterone and bevacizumab
      on regression of surgically endometriotic implants in rats.
AB  - This study hypothesizes that oral rosuvastatin, oral dienogest and
      intraperitoneal bevacizumab might improve endometriosis in randomly selected
      female Wistar albino rats with surgically endometriotic implants. Thirty female
      Wistar albino rats with surgically endometriotic implants were randomized into
      three treatment groups: oral rosuvastatin (20 mg kg/day; oral rosuvastatin group
      1; n = 10), oral progesterone (dienogest group 2; n = 10) and intraperitoneal
      bevacizumab (2.5 mg/kg of single intraperitoneal injection of bevacizumab;
      bevacizumab group 3; n = 10), for 10 days. Post-treatment variables were
      compared. The oral rosuvastatin group showed higher reduction for the glandular
      epithelium and uterine vessels of histopathological scores values than the oral
      progesterone group (both, p < 0.017, respectively). The median glandular
      epithelium and uterine vessels and histopathological scores values did not show a
      statistically significant difference between group 1 and group 3 (p > 0.017).
      Endometrial thickness values and uterine volume values were more significantly
      reduced in the oral rosuvastatin group than the oral progesterone group (both, p
      < 0.017, respectively). Moreover, endometrial thickness and uterine volume values
      were not different in groups wecompared with group 3 (p > 0.017). In conclusion,
      oral rosuvastatin and intraperitoneal injection of bevacizumab may cause more
      significant regression of surgically endometriotic implants in rats than oral
      progesterone medications.

PMID- 28452241
TI  - Respiratory monitoring in adult intensive care unit.
AB  - INTRODUCTION: The mortality of patients with respiratory failure has steadily
      decreased with the advancements in protective ventilation and treatment options.
      Although respiratory monitoring per se has not been proven to affect the
      mortality of critically ill patients, it plays a crucial role in patients' care,
      as it helps to titrate the ventilatory support. Several new monitoring techniques
      have recently been made available at the bedside. The goals of monitoring
      comprise alerting physicians to detect the change in the patients' conditions, to
      improve the understanding of pathophysiology to guide the diagnosis and provide
      cost-effective clinical management. Areas covered: We performed a review of the
      recent scientific literature to provide an overview of the different methods used
      for respiratory monitoring in adult intensive care units, including bedside
      imaging techniques such as ultrasound and electrical impedance tomography. Expert
      commentary: Appropriate respiratory monitoring plays an important role in
      patients with and without respiratory failure as a guiding tool for the
      optimization of ventilation support, avoiding further complications and
      decreasing morbidity and mortality. The physician should tailor the monitoring
      strategy for each individual patient and know how to correctly interpret the
      data.

PMID- 28452242
TI  - The Homecare Aide Workforce Initiative: Implementation and Outcomes.
AB  - Improved training and support are thought to improve retention among direct care
      workers. However, few studies have examined actual retention. This study examined
      satisfaction and retention among home health aides enrolled in the "Homecare Aide
      Workforce Initiative" (HAWI) at three New York agencies. Data included surveys of
      HAWI trainees and new hires and payroll data for HAWI graduates and others. Three
      months after hire, 91% of HAWI hires reported they were "very satisfied" or
      "satisfied" with the job; 57% reported they were "not at all likely" to leave
      their job in the coming year. At 365 days, 60% were still working. In logistic
      regression, the odds of being retained at 3, 6, and 12 months were significantly
      higher among HAWI graduates than non-HAWI new hires. Although not a randomized
      trial, the study demonstrates an association between participation in an
      innovative entry-level workforce program and superior 3-, 6-, and 12-month
      retention.

PMID- 28452243
TI  - Evaluation of US 2016/0115161 A1: isoindoline compounds and methods of their use.
AB  - INTRODUCTION: Immunomodulatory drugs (IMIDs(r)) are small orally available
      molecules that modulate the immune system and other biological targets through
      multiple mechanisms of action and have been successfully used in the treatment of
      myelodysplastic syndrome and multiple myeloma. However, recent studies of their
      complex mechanism of action revealed their potential in autoimmune diseases and
      solid tumors, which intensified scientific interest in these compounds. Areas
      covered: This patent application claims new IMIDs for the treatment of cancer and
      disorders associated with angiogenesis and inflammation. Substitution of
      isoindolinone ring on position 5 with urea and amide linkers connected to
      different aromatic rings lead to very potent inhibitors of TNF-alpha production
      with antiproliferative activities against Nemalwa cells and against colorectal,
      pancreatic, prostate and breast cancer cell lines in sub-nano to low-nanomolar
      concentration range. Expert opinion: Substitution of position 5 on the
      isoindolinone ring, which is presented in this invention, is currently the hot
      spot of Celgene's research. Results of biological tests, which are superior over
      those of presently used IMIDs lenalidomide and pomalidomide, make these compounds
      viable leads for future development of new anticancer drugs against blood and
      solid cancers.

PMID- 28452245
TI  - Litvinenko - a very expensive poison.

PMID- 28452244
TI  - Efficacy of double mirrored omega pattern for skin sparing mastectomy to reduce
      ischemic complications.
AB  - BACKGROUND: Excellent cosmetic results from skin-sparing mastectomy (SSM) are
      often impaired by skin flaps' necrosis (SFN), from 8%-25% or worse in smokers.
      This study prospectively investigated the efficacy of Double-Mirrored Omega
      Pattern (DMOP-SSM) compared to Wise Pattern SSM (WP-SSM) for immediate
      reconstruction in moderate/large-breasted smokers. METHODS: From 2008-2010, DMOP
      SSM was performed in 51 consecutive immediate breast reconstructions on 41
      smokers (mean age = 49.8 years) with moderate/large and ptotic breasts. This
      active group (AG) was compared to a similar historical control group (CG) of 37
      smokers (mean age = 51.1 years) who underwent WP-SSM and immediate breast
      reconstruction, with a mean follow-up of 37.6 months. Skin ischaemic
      complications, number of surgical revisions, time to wound healing, and patient
      satisfaction were analysed. Descriptive statistics were reported and comparison
      of performance endpoints was performed using Fisher's exact test and Mann-Whitney
      U-test. A p-value <.05 was considered significant. RESULTS: Patients' mean age (p
      = .316) and BMI (p = .215) were not statistically different between groups.
      Ischaemic complications occurred in 11.7% of DMOP-SSMs and in 32.4% of WP-SSMs (p
      = .017), and revision rates were, respectively, 5.8% and 24.3% (p = .012), both
      statistically significant. Mean time to wound healing was, respectively, 16.8
      days and 18.4 days (p = .205). Mean patients' satisfaction scores were,
      respectively, 18.9 and 21.1, statistically significant (p = .022). CONCLUSION:
      Although tobacco use in moderate/large breasted patients can severely impair
      outcomes of breast reconstruction, the DMOP-SSM approach, compared to WP-SSM,
      allows smokers to benefit from SSM, but with statistically significant reduced
      skin flaps ischaemic complications, revision surgery, and better cosmetic
      outcomes.

PMID- 28452246
TI  - Beatification of Cardinal Henry Newman.
AB  - Claims of a miracle cure require objective and thorough investigation with a
      review of all contemporaneous medical records. This paper describes instances of
      apparent miraculous recoveries from fatal or incurable illnesses. Following more
      rigorous review of the medical documentation, when available, a different story
      emerges. Misdiagnosis and/or appropriate treatment account for the best cases.

PMID- 28452247
TI  - Predictive value of repeated measurements of luteal progesterone and estradiol
      levels in patients with intrauterine insemination and controlled ovarian
      stimulation.
AB  - OBJECTIVE: The objective of this study is to assess if the difference of repeated
      measurements of estradiol and progesterone during luteal phase predict the
      outcome of intrauterine insemination. DESIGN: Prospective study. SETTING:
      Reproductive clinic. PATIENTS: 126 patients with infertility. INTERVENTION(S):
      Patients underwent controlled ovarian stimulation with recombinant FSH (50-150
      IU/d). The day of IUI patients were given p.o natural micronized progesterone in
      a dose of 100 mg/tds. RESULTS: The area under the receiver characteristic
      operating curve (ROC curve) in predicting clinical pregnancy for % change of
      estradiol level on days 6 and 10 was 0.892 with 95% CI: 0.82-0.94. A cutoff value
      of change > -29.5% had a sensitivity of 85.7 with a specificity of 90.2. The
      corresponding ROC curve for % change of progesterone level was 0.839 with 95% CI:
      0.76-0.90. A cutoff value of change > -33% had a sensitivity of 85 with a
      specificity of 75. CONCLUSIONS: The % change of estradiol and progesterone
      between days 6 and 10 has a predictive ability of pregnancy after IUI with COS of
      89.2% and 83.4%, respectively. The addition of % of progesterone to % change of
      estradiol does not improve the predictive ability of % estradiol and should not
      be used.

PMID- 28452248
TI  - Response of aquatic protists to electric field exposure.
AB  - PURPOSE: To test the effects of short-term exposure of aquatic organisms to
      electric field (EF) with negligible magnetic component. MATERIALS AND METHODS: We
      built a plate capacitor that served as a source of EF of strengths that can be
      found in nature near transmission lines. We exposed two cultured protist species
      Euglena viridis and Paramecium caudatum to EFs for 24 hours and monitored their
      abundance, morphology, intracellular superoxide anion (by dihydroethidium [DHE]),
      hydrogen peroxide by (H2DCF) and lipid peroxidation (MDA) contents, catalase
      (CAT) and superoxide dismutase (SOD) activity. RESULTS: We found that even short
      term exposure to low strength EF causes changes in population abundance,
      morphology and oxidative stress response in both species. As the EF strength
      increased, abundance of both species decreased. However, at weaker EFs, fission
      rates were seemingly promoted. We noted a decrease in size in both organisms in
      directions perpendicular to their fission planes correlated with EF strength. DHE
      and H2DCF fluorescence intensity and SOD activity were higher in organisms
      exposed to the stronger EFs. CONCLUSIONS: We suggest that the electric component
      of the field, rather than the magnetic, is the main cause of all the noted
      effects. As a result, aquatic organisms should be given greater importance in
      studies assessing the effects of EMFs in spite of the attenuating effects of
      water to EF strengths.

PMID- 28452249
TI  - 6,7,3',4'-Tetrahydroxyisoflavone improves the survival of whole-body-irradiated
      mice via restoration of hematopoietic function.
AB  - PURPOSE: 6,7,3',4'-tetrahydroxyisoflavone (T3) is a novel chemically synthesized
      compound reported in our previous study. This study was designed to explore the
      radioprotective effect of T3, and if so, its potential mechanisms. MATERIALS AND
      METHODS: KunMing mice were exposed to various doses of gamma irradiation (60 Co)
      after being treated with dimethyl sulfoxide (DMSO) or T3. Briefly, survival rate,
      dose reducing factor (DRF), body weight change (%), spleen index (SI) and thymus
      index (TI) of irradiated mice with or without different doses of T3 treatment
      were evaluated routinely. The hematopoietic function of bone marrow was
      emphatically investigated. In vitro experiments were performed to observe the
      protective effect of T3 on irradiated human lymphocyte AHH-1 cells by cell
      viability or flow cytometry (FCM) assays. RESULTS: A single dose of subcutaneous
      administration of T3 significantly improved the survival rate, and enhanced the
      restoration of hematopoietic function in irradiated mice. T3 also decreased the
      apoptosis of irradiated AHH-1 cells in vitro. CONCLUSIONS: T3 protected mice
      against lethal gamma irradiation-induced injury probably through the restoration
      of hematopoietic function. This implied that T3 could be further developed as a
      radioprotector.

PMID- 28452250
TI  - Implementation of a Complex Intervention to Support Leadership Development in
      Nursing Homes: A Multimethod Participatory Study.
AB  - Leadership is key to quality improvement in nursing homes. This article reports
      on the initial analysis of the transformational My Home Life Leadership Support
      program for nursing home managers being implemented in Scotland. It analyses
      learning from a multimethod participatory descriptive study. Contribution
      analysis theory informed the evaluation. Evidence-Based Practice, Relationship
      Centered Care, Appreciative Inquiry, and Caring Conversations informed the
      intervention to develop transformational leadership. Data generation methods
      included baseline and postintervention questionnaires to describe culture change
      within the study population, together with more in-depth qualitative data
      generated from group discussions throughout the leadership support program.
      Qualitative data analysis was an iterative collaborative process with
      participants to generate themes about the impact of the program on themselves and
      their practice. Data showed positive changes in managers' perceptions of their
      self-awareness, leadership communication and relationship skills, and development
      of positive cultures. This model offers lessons for those interested in ways to
      approach the emotional, educational, and cultural dynamics of change in other
      human service contexts.

PMID- 28452251
TI  - Mutual Distrust: Perspectives From Researchers and Policy Makers on the Research
      to Policy Gap in 2013 and Recommendations for the Future.
AB  - The production of health policy-relevant research is necessary, but not
      sufficient, to promote its utilization in policy. Our objective was to understand
      the perspectives of United States' state-level policy makers and health
      researchers on the barriers and facilitators to the translation of health
      evidence into the policy process, with a particular focus on issues related to
      relationship building. We conducted interviews with 215 US health services and
      health policy researchers and 40 state-level staffers and legislators.
      Researchers and policy makers faced the same major barrier to research
      translation: lack of dedicated time to do so. Some policy makers questioned the
      credibility of research, and researchers questioned policy makers' authentic
      desire to use evidence in decision making. For some study participants, a mutual
      mistrust of the other group challenges stronger relationship formation.
      Interventions are needed to help both groups understand a broader role that
      research plays in policy making and to increase personal contact, and ultimately
      trusted relationships, across various actors in the policy process.

PMID- 28452252
TI  - Systematic development of design of experiments (DoE) optimised self
      microemulsifying drug delivery system of Zotepine.
AB  - The aim of present investigation is to improve dissolution rate of poor soluble
      drug Zotepine by a self-microemulsifying drug delivery system (SMEDDS). Ternary
      phase diagram with oil (Oleic acid), surfactant (Tween 80) and co-surfactant (PEG
      400) at apex were used to identify the efficient self-microemulsifying region.
      Box-Behnken design was implemented to study the influence of independent
      variables. Principal Component Analysis was used for scrutinising critical
      variables. The liquid SMEDDS were characterised for macroscopic evaluation, %
      Transmission, emulsification time and in vitro drug release studies. Optimised
      formulation OL1 was converted in to S-SMEDDS by using Aerosil(r) 200 as an
      adsorbent in the ratio of 3:1. The S-SMEDDS was characterised by SEM, DSC,
      globule size (152.1 nm), zeta-potential (-28.1 mV), % transmission study
      (98.75%), in vitro release (86.57%) at 30 min. The optimised solid SMEDDS
      formulation showed faster drug release properties as compared to conventional
      tablet of Zotepine.

PMID- 28452253
TI  - Radiation dose rate affects the radiosensitization of MCF-7 and HeLa cell lines
      to X-rays induced by dextran-coated iron oxide nanoparticles.
AB  - BACKGROUND AND PURPOSE: The aim of radiotherapy is to deliver lethal damage to
      cancerous tissue while preserving adjacent normal tissues. Radiation absorbed
      dose of the tumoral cells can increase when high atomic nanoparticles are present
      in them during irradiation. Also, the dose rate is an important aspect in
      radiation effects that determines the biological results of a given dose. This in
      vitro study investigated the dose-rate effect on the induced radiosensitivity by
      dextran-coated iron oxide in cancer cells. MATERIALS AND METHODS: HeLa and MCF-7
      cells were cultured in vitro and incubated with different concentrations of
      dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV
      photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain
      the cells' survival after 48 h of irradiations. RESULTS: Incubating the cells
      with the nanoparticles at concentrations of 10, 40 and 80 MUg/ml showed no
      significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed
      more radiosensitivity effect by increasing the dose rate and nanoparticles
      concentration. Radiosensitization enhancement factors of MCF-7 and HeLa cells at
      a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 MUg/ml were
      1.21 +/- 0.06 and 1.19 +/- 0.04, respectively. CONCLUSION: Increasing the dose
      rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the
      radiosensitization induced by the dextran-coated iron nanoparticles in these
      cells.

PMID- 28452254
TI  - The effect of TiO2 coating on biological NiTi alloys after micro-arc oxidation
      treatment for corrosion resistance.
AB  - NiTi alloys exhibit good properties, such as shape memory behavior, high
      corrosion resistant, having the closest elasticity modulus of a human bone and
      superior biocompatibility properties. However, the surface problems that arise
      during the use of this alloy limit the usage in the industry and health sector.
      In recent years, micro-arc oxidation method is used to improve the surface
      properties and increase the usage of these alloys. In this study, the TiO2
      coatings were deposited on the NiTi substrates. The surface topography,
      morphology, crystallographic structure, and thickness of the coatings were
      determined using scanning electron microscopy and X-ray diffraction. The
      corrosion properties were investigated using potentiostat test unit in two
      different media such as NaCl solution and simulated body fluid. The results show
      that the coated samples have higher corrosion resistance than uncoated samples in
      the two different media.

PMID- 28452255
TI  - Effect of physical workload and modality of information presentation on pattern
      recognition and navigation task performance by high-fit young males.
AB  - Many occupations require both physical exertion and cognitive task performance.
      Knowledge of any interaction between physical demands and modalities of cognitive
      task information presentation can provide a basis for optimising performance.
      This study examined the effect of physical exertion and modality of information
      presentation on pattern recognition and navigation-related information
      processing. Results indicated males of equivalent high fitness, between the ages
      of 18 and 34, rely more on visual cues vs auditory or haptic for pattern
      recognition when exertion level is high. We found that navigation response time
      was shorter under low and medium exertion levels as compared to high intensity.
      Navigation accuracy was lower under high level exertion compared to medium and
      low levels. In general, findings indicated that use of the haptic modality for
      cognitive task cueing decreased accuracy in pattern recognition responses.
      Practitioner Summary: An examination was conducted on the effect of physical
      exertion and information presentation modality in pattern recognition and
      navigation. In occupations requiring information presentation to workers, who are
      simultaneously performing a physical task, the visual modality appears most
      effective under high level exertion while haptic cueing degrades performance.

PMID- 28452256
TI  - Secondary traumatic stress in emergency medicine clinicians.
AB  - Previously called Secondary Traumatic Stress (STS), secondary exposure to trauma
      is now considered a valid DSM-5 Criterion A stressor for posttraumatic stress
      disorder (PTSD). Previous studies have found high rates of STS in clinicians who
      treat traumatically injured patients. However, little research has examined STS
      among Emergency Medicine (EM) physicians and advanced practice providers (APPs).
      The current study enrolled EM providers (N = 118) working in one of 10 hospitals
      to examine risk factors, protective factors, and the prevalence of STS in this
      understudied population. Most of the participants were physicians (72.9%),
      Caucasian (85.6%), and male (70.3%) with mean age of 39.7 (SD = 8.9). Overall,
      12.7% of the sample screened positive for STS with clinical levels of intrusion,
      arousal, and avoidance symptom clusters, and 33.9% had at least one symptom
      cluster at clinical levels. Low resilience and a history of personal trauma were
      positively associated with positive STS screens and STS severity scores.
      Borderline significance suggested that female gender and spending >=10% of one's
      time with trauma patients could be additional risk factors. Findings suggest that
      resilience-building interventions may be beneficial.

PMID- 28452257
TI  - Updates on the pathophysiology and treatment of aplastic anemia: a comprehensive
      review.
AB  - INTRODUCTION: The past decade or longer has witnessed an acceleration in our
      understanding of previously developed immune system and clonal evolution
      mechanisms, and the genesis of more novel concepts of telomere attrition. Many of
      these concepts are steadily finding their way into translation in various aspects
      of clinical practice, and provide prospects to improve AA management and inform
      therapeutic strategy development. In this review, we intend to discuss the
      pathophysiology and treatments with an emphasis on most recent developments to
      provide an update on our understanding of disease mechanisms. Areas covered: A
      literature search was undertaken addressing various aspects of pathophysiology
      with a focus on the role of immune system repertoire, telomeres and mutational
      events surrounding AA. We also reviewed upon the temporal evolution of treatment
      strategies in AA to the contemporary management of today and commented briefly
      upon the more recently investigated novel therapies and their expanding niche
      especially in the transplant and salvage setting. Expert commentary: Immune
      mediated destruction of hematopoietic stem and progenitor cells, leading to a
      marrow devoid of hematopoietic elements, and peripheral pancytopenia are the
      hallmarks of AA. Recent studies have shed light on another facet of the disease -
      as a clonal disorder characterized by karyotypic abnormalities, genomic
      instability, telomere attrition, and recurrent somatic mutations reminiscent of
      myeloid malignancies. Further understanding of this underlying pathophysiology
      can help in improving prognostication and treatment of this disease.

PMID- 28452259
TI  - Nurse had 'impaired' fitness to practise.
AB  - A nurse has been reprimanded by the Nursing and Midwifery Council (NMC) aft er
      depriving a care home resident of 'any chance he had to survive', by failing to
      commence cardiopulmonary resuscitation (CPR).

PMID- 28452258
TI  - Care home staff need training in gender identity, says report.
AB  - Health and social care professionals need better training on sexuality and gender
      identity issues relating to lesbian, gay, bisexual and trans (LGBT) people with
      dementia, a report recommends.

PMID- 28452260
TI  - Scotland consults on workload law.
AB  - The Scottish Government has launched a consultation to introduce safe nurse
      staffing legislation.

PMID- 28452261
TI  - Impartial advice on stroke and brain injury apps.
AB  - Specialist nurses and patients have joined forces to create a website to review
      apps for those with stroke or brain injuries.

PMID- 28452262
TI  - Advance care planning.
AB  - Advance care planning (ACP) is a structured discussion about a person's wishes
      and thoughts for the future, and is recognised as a vital part of good care at
      the end of life ( Department of Health 2008 , Royal College of Physicians et al
      2009 , General Medical Council 2010 ).

PMID- 28452263
TI  - We need a new culture of care for older people.
AB  - With the proportion of the population over 65 years set to rise to one in five
      people by 2030, the need and demand for skilled health and social care
      practitioners is expected to rise too. An effective future workforce must promote
      health, well-being and self-care in later life, while managing the consequences
      of frailty, long-term conditions and co-morbidities in an ageing population.

PMID- 28452264
TI  - Dementia Care: A Practical Approach Smith Grahame (Ed) Dementia Care: A Practical
      Approach 185pp L24.99 CRC Press 9781482245738 1482245736 [Formula: see text].
AB  - This comprehensive overview of dementia care is supported by research-based
      evidence. Each chapter is well structured and provides a scenario, a summary and
      points for reflection.

PMID- 28452265
TI  - 'I love complexity'.
AB  - Why did you become a nurse? I had a career in banking which was well paid and
      exciting, but essentially unrewarding. My neighbours were both nurses and
      suggested it might suit me.

PMID- 28452266
TI  - Yoga can improve older people's mental health.
AB  - Yoga has consistently yielded encouraging results in the treatment of generalised
      anxiety disorder and panic disorder, and has also been shown to improve mood and
      decrease symptoms of depression.

PMID- 28452267
TI  - Spirituality and Coping with Loss: End of Life Healthcare Practice Greenstreet
      Wendy Spirituality and Coping with Loss: End of Life Healthcare Practice 160pp
      L25.99 CRC Press 9781785231483 1785231480 [Formula: see text].
AB  - Sometimes a book that seems at first rather densely written, and more concerned
      with theory than practice, develops into a fascinating and valuable text for
      academic and practising nurses. This is such a book.

PMID- 28452268
TI  - Being research-savvy in acute care settings.
AB  - We are good at reinventing the wheel in older people's nursing, where we often
      find ourselves struggling with the same practice issues regardless of care
      setting. Frequently, the starting point is to develop a local solution.

PMID- 28452270
TI  - Eyeball exercise can improve balance ability in older people.
AB  - Having falls can lead to loss of self-confidence, increased dependence on others
      and decreased quality of life. Older people have a higher risk of falls due to
      decreased flexibility, weakness of lower leg muscles, failing eyesight and poor
      balance.

PMID- 28452271
TI  - Supporting insulin initiation in type 2 diabetes in primary care.
AB  - The global epidemic of type 2 diabetes demands innovation in care delivery.
      Guidelines recommend early adoption of insulin as part of a stepwise treatment to
      bring glycated haemoglobin (HbA1c) below the target of 7% (53mmol/mol) to reduce
      long-term complications.

PMID- 28452272
TI  - How we transformed the care of people with Parkinson's disease.
AB  - Cardiff and Vale University Health Board's (CVUHB) Parkinson's disease (PD)
      service cares for nearly 1,000 people who have the disease in Cardiff and parts
      of the Vale of Glamorgan in Wales.

PMID- 28452273
TI  - Poor care and the professional duty of the registered nurse.
AB  - Concerns have been raised in recent years about standards of care in the UK.
      Notable failures have been identified in the care of vulnerable older adults.
      This article identifies and discusses some logical steps which might be taken to
      minimise the risk of individual and systemic care failure in settings for older
      adults. These steps include frank discussion about ageism to promote empowerment
      and respect for older people; ensuring robust policies are in place that support
      and encourage the reporting of poor care; and ensuring that registered
      practitioners are aware of their accountability for their actions and also their
      omissions should they witness poor care. In addition to reducing the risk of poor
      care, these steps could contribute to having a more confident, competent and
      empowered workforce.

PMID- 28452274
TI  - An innovative approach to hydration for a patient with dementia.
AB  - Nursing older people in acute settings involves the provision of complex care,
      including the maintenance of good hydration. Dehydration is a serious condition
      that may contribute to the development of pressure ulcers, urinary tract
      infections, acute kidney injury and venous thromboembolism. If oral hydration
      methods are not successful, the alternatives are intravenous (IV) or subcutaneous
      fluid hydration therapy. These are invasive methods and may not be tolerated by
      all patients. This article uses a case study to explore an innovative approach to
      oral hydration. The intervention was developed for Roy, a patient with advanced
      Alzheimer's disease, who had a reduced fluid intake and who became agitated when
      staff or family members attempted to assist him with nutrition and hydration. It
      involved consultation with Roy's family and the introduction of a flavoured drink
      to encourage the patient to drink. His weekly fluid intake doubled as a result
      and the intervention avoided the use of alternative invasive rehydration therapy.
      Although this was a local initiative developed for one patient, it is an example
      of how a person - entred, collaborative approach can have a positive effect for
      patients.

PMID- 28452275
TI  - Older people lack access to psychological therapies, says healthcare regulator.
AB  - A senior NHS inspector has said that older people in parts of England have no
      access to specialist psychological therapies.

PMID- 28452276
TI  - A new theme: What Can You Do?
AB  - Dying Matters Awareness Week has been running since 2009 and has always been
      rooted in conversation.

PMID- 28452278
TI  - MPs demand urgent review of social care funding.
AB  - The timing was uncanny. First came the upbeat tone of NHS England's progress
      report on its 2014 Five Year Forward View.

PMID- 28452280
TI  - Chronic obstructive pulmonary disease.
AB  - Essential facts An estimated three million people have chronic obstructive
      pulmonary disease (COPD) in the UK, but less than one third are diagnosed. COPD
      refers to a group of lung conditions that make it difficult to empty air out of
      the lungs because the airways have narrowed.

PMID- 28452281
TI  - Assessment, prevention and management of skin tears.
AB  - Skin tears are common in older people. They are acute wounds that are at high
      risk of becoming complex, chronic wounds due to the interplay between the
      physiological changes in the skin and trauma from the external environment. Skin
      tears have been reported to have prevalence rates equal to, or greater than,
      those for pressure ulcers. A comprehensive risk assessment should include
      assessment of the individual's general health (chronic/critical disease,
      polypharmacy and cognitive, sensory and nutritional status); mobility (history of
      falls, impaired mobility, dependent activities of daily living, and mechanical
      trauma); and skin (extremes of age, fragile skin and previous skin tears). A
      recognised classification system should be used to identify and document skin
      tears and guide treatment decisions in line with local wound management
      protocols. Nurses and carers are in a prime position to prevent, assess and
      manage skin tears.

PMID- 28452282
TI  - Letter to the Editor: Re: Is Trying to Quit Associated With Tooth Loss and
      Delayed Yearly Dental Visit Among Smokers? Results of the 2014 Behavioral Risk
      Factor Surveillance.

PMID- 28452283
TI  - Authors' Response.

PMID- 28452284
TI  - SHRINK in the CLOUDS: the recollections of an aviation psychologist.

PMID- 28452286
TI  - Clock Gene Expression in the Suprachiasmatic Nucleus of Hibernating Arctic Ground
      Squirrels.
AB  - Most organisms have a circadian system, entrained to daily light-dark cycles,
      that regulates 24-h rhythms of physiology and behavior. It is unclear, however,
      how circadian systems function in animals that exhibit seasonal metabolic
      suppression, particularly when this coincides with the long-term absence of a day
      night cycle. The arctic ground squirrel, Urocytellus parryii, is a medium-sized,
      semi-fossorial rodent that appears above-ground daily during its short active
      season in spring and summer before re-entering a constantly dark burrow for 6 to
      9 months of hibernation. This hibernation consists of multiple week-long torpor
      bouts interrupted by short (< 20 h) arousal intervals when metabolism and body
      temperature (Tb) return to normal levels. Here, we used immunohistochemistry to
      measure the expression of daily or circadian rhythms of the protein products of 3
      circadian clock genes, PER1, PER2, BMAL1, and the neural activity marker c-FOS in
      the suprachiasmatic nucleus (SCN) of arctic ground squirrels before, during, and
      after the first torpor bout of hibernation. Before torpor, while under 12:12-h
      light:dark conditions, animals showed significant daily rhythms in their Tb, as
      well as in protein expression levels of PER1 and PER2, but not BMAL1. Upon
      entering first torpor (Tb < 30 degrees C), animals were moved into constant
      darkness. When sampled at 6-h intervals-beginning 24 h after the last light out,
      with Tb 3 degrees C to 4 degrees C-there were no circadian oscillations in PER1,
      PER2, or c-FOS expression. Sampling across 24 h during the first spontaneous
      arousal interval, c-FOS expression was elevated only when Tb reached 20 degrees C
      and PER1 and PER2 expression did not show any Tb- or time-dependent changes.
      These results suggest that the central circadian clock might have stopped
      functioning during hibernation in this species, and the timing of arousal from
      torpor in arctic ground squirrels is unlikely to be controlled by the circadian
      clock within the SCN.

PMID- 28452285
TI  - Daily Light Exposure Patterns Reveal Phase and Period of the Human Circadian
      Clock.
AB  - Light is the most potent time cue that synchronizes (entrains) the circadian
      pacemaker to the 24-h solar cycle. This entrainment process is an interplay
      between an individual's daily light perception and intrinsic pacemaker period
      under free-running conditions. Establishing individual estimates of circadian
      phase and period can be time-consuming. We show that circadian phase can be
      accurately predicted (SD = 1.1 h for dim light melatonin onset, DLMO) using 9
      days of ambulatory light and activity data as an input to Kronauer's limit-cycle
      model for the human circadian system. This approach also yields an estimated
      circadian period of 24.2 h (SD = 0.2 h), with longer periods resulting in later
      DLMOs. A larger amount of daylight exposure resulted in an earlier DLMO.
      Individuals with a long circadian period also showed shorter intervals between
      DLMO and sleep timing. When a field-based estimation of tau can be validated
      under laboratory studies in a wide variety of individuals, the proposed methods
      may prove to be essential tools for individualized chronotherapy and light
      treatment for shift work and jetlag applications. These methods may improve our
      understanding of fundamental properties of human circadian rhythms under daily
      living conditions.

PMID- 28452287
TI  - Akt1 Controls the Timing and Amplitude of Vascular Circadian Gene Expression.
AB  - The AKT signaling pathway is important for circadian rhythms in mammals and flies
      ( Drosophila). However, AKT signaling in mammals is more complicated since there
      are 3 isoforms of AKT, each performing slightly different functions. Here we
      study the most ubiquitous AKT isoform, Akt1, and its role at the organismal level
      in the central and vascular peripheral clocks. Akt1-/- mice exhibit relatively
      normal behavioral rhythms with only minor differences in circadian gene
      expression in the liver and heart. However, circadian gene expression in the Akt1
      /- aorta, compared with control aorta, follows a distinct pattern. In the Akt1-/-
      aorta, positive regulators of circadian transcription have lower amplitude
      rhythms and peak earlier in the day, and negative circadian regulators are
      expressed at higher amplitudes and peak later in the day. In endothelial cells,
      negative circadian regulators exhibit an increased amplitude of expression, while
      the positive circadian regulators are arrhythmic with a decreased amplitude of
      expression. This indicates that Akt1 conditions the normal circadian rhythm in
      the vasculature more so than in other peripheral tissues where other AKT isoforms
      or kinases might be important for daily rhythms.

PMID- 28452289
TI  - Road traffic injury among child motorcyclists in Vientiane Capital, Laos: a cross
      sectional study using a hospital-based injury surveillance database.
AB  - This study investigated the distribution of motorcyclists, including drivers and
      passengers, who were involved in road traffic crashes and admitted to hospital in
      Vientiane Capital, Laos. The focus was on child motorcycle drivers and passengers
      under 15 years. A hospital-based injury surveillance database in Vientiane
      Capital was used. The surveillance was performed in two hospitals. From 1
      September to 31 December 2009, 3968 patients were admitted to the participating
      hospitals with road traffic injuries. Patients under 15 years accounted for 10.8%
      (427/3968). The majority of patients under 15 years were motorcycle drivers or
      passengers (71.7%, 306/427). Child motorcyclists including drivers and passengers
      were less likely to wear a helmet than adults (adjusted odds ratio [OR], 0.3, 95%
      confidence interval [CI], 0.2-0.5, for children 10-14 years; adjusted OR: 0.1,
      95% CI, 0.05-0.4, for children under 10 years). It is suggested that stricter
      regulation enforcement for child motorcycle drivers and passengers may be needed.
      In addition, barriers against wearing helmets for motorcycle drivers and
      passengers in Laos should also be examined in further studies.

PMID- 28452288
TI  - 25(OH)D levels in trained versus sedentary university students at 64 degrees 
      north.
AB  - PURPOSE: 25-hydroxyvitamin D (25[OH]D) deficiency is associated with compromised
      bone mineralisation, fatigue, suppressed immune function and unsatisfactory
      skeletal muscle recovery. We investigated the risk of 25(OH)D insufficiency or
      deficiency in endurance athletes compared to sedentary non-athletes living at 64
      degrees  north. METHODS: University student-athletes (TS) and sedentary students
      (SS) volunteered to participate in this study. TS engaged in regular exercise
      while SS exercised no more than 20 minutes/week. Metabolic Equivalent of Task
      (MET) scores for participants were determined. Vitamin D intake was assessed
      using the National Cancer Institute's 24-hour food recall (ASA24). Fasting plasma
      25(OH)D levels were quantified via enzyme-linked immunosorbent assay. RESULTS: TS
      reported higher activity levels than SS as assessed with MET-minutes/week and
      ranking of physical activity levels (p < 0.05). The reported mean daily intake of
      vitamin D was higher in TS compared to SS (p < 0.05) while 25(OH)D plasma levels
      were lower in TS than in SS (p < 0.05). In total, 43.8% of the TS were either
      insufficient (31.3%) or deficient (12.5%) in 25(OH)D, while none of the SS were
      insufficient and 13.3% were deficient. CONCLUSION: TS are at increased risk of
      25(OH)D insufficiency or deficiency compared to their sedentary counterparts
      residing at the same latitude, despite higher vitamin D intake.

PMID- 28452291
TI  - Bioavailability of iron multi-amino acid chelate preparation in mice and human
      duodenal HuTu 80 cells.
AB  - Strategies for preventing Fe deficiency include Fe supplementation and Fe
      fortification of foods. The absorption, metabolism and chemical characteristics
      of Fe multi-amino acid chelate (IMAAC) are not known. Absorption of IMAAC was
      compared with FeSO4 in Fe-depleted mice and in vitro chemical studies of the Fe
      supplement was performed in HuTu 80 cells. Hb repletion study was carried out in
      Fe-deficient CD1 mice that were fed for 10 d a diet supplemented with ferrous
      IMAAC or FeSO4. A control group of Fe-replete mice was fed a diet with adequate
      Fe concentrations throughout the study. Tissues were collected from the mice, and
      the expression of Fe-related genes was determined by quantitative PCR. Ferric
      reductase and Fe uptake were evaluated in HuTu 80 cells. Supplementation of the
      diet with FeSO4 or IMAAC significantly increased Hb levels (P<0.001) in Fe
      deficient mice from initial 93.9 (SD 10.8) or 116.2 (SD 9.1) to 191 (SD 0.7) or
      200 (SD 0.5) g/l, respectively. Initial and final Hb for the Fe-deficient control
      group were 87.4 (SD 6.7) and 111 (SD 11.7) g/l, respectively. Furthermore, the
      liver non-haem Fe of both supplement groups increased significantly (P<0.001).
      IMAAC was more effective at restoring Fe in the spleen compared with FeSO4
      (P<0.005). Gene expression showed the IMAAC supplement absorption is regulated by
      the body's Fe status as it significantly up-regulated hepcidin (P<0.001) and down
      regulated duodenal cytochrome b mRNA (P<0.005), similar to the effects seen with
      FeSO4. A significant proportion of Fe in IMAAC is reduced by ascorbic acid. Fe
      absorption in mice and cells was similar for both IMAAC and FeSO4 and both
      compounds induce and regulate Fe metabolism genes similarly in the maintenance of
      homeostasis in mice.

PMID- 28452292
TI  - Body weight and body composition changes during military training and deployment
      involving the use of combat rations: a systematic literature review.
AB  - Dismounted military personnel operate in physically and psychologically demanding
      environments, with energy intake from combat rations often falling short of their
      requirements, leading to reductions in body weight and changes in body
      composition, which can impact both their health and performance. This review
      systematically investigated the effects of the continual use of combat rations
      for periods of 3-40 d on body weight and/or body composition in military
      personnel engaged in training or deployment. In all, ten databases were searched
      from their inception until October 2016. Outcome data were described narratively,
      with studies assessed for quality and risk of bias. A total of thirty studies
      undertaken over 3-34 d were included. Studies were rated positive, neutral or
      negative in quality according to the Academy of Nutrition and Dietetics Quality
      Checklist, with many at risk of bias. Reductions in mean body weight varied, from
      a negligible decrease of 0.1 % during 8 d of combat training to a substantial
      decrease of approximately 8.3 % during 12 d of energy restriction during a US
      Army Ranger course. Decreases in fat mass, fat-free mass and percentage body fat
      were also reported. There is thus evidence that the continual use of combat
      rations for periods of 3-34 d results in reductions in body weight and body
      composition changes which, in some scenarios, may impact on the performance of
      troops. Body weight and composition should be routinely monitored before and
      after field activities, and at more regular intervals depending on the length,
      intensity and type of activity being undertaken.

PMID- 28452293
TI  - Separation of foot-and-mouth disease virus leader protein activities;
      identification of mutants that retain efficient self-processing activity but
      poorly induce eIF4G cleavage.
AB  - Foot-and-mouth disease virus is a picornavirus and its RNA genome encodes a large
      polyprotein. The N-terminal part of this polyprotein is the leader protein, a
      cysteine protease, termed Lpro. The virus causes the rapid inhibition of host
      cell cap-dependent protein synthesis within infected cells. This results from the
      Lpro-dependent cleavage of the cellular translation initiation factor eIF4G. Lpro
      also releases itself from the virus capsid precursor by cleaving the L/P1
      junction. Using site-directed mutagenesis of the Lpro coding sequence, we have
      investigated the role of 51 separate amino acid residues in the functions of this
      protein. These selected residues either are highly conserved or are charged and
      exposed on the protein surface. Using transient expression assays, within BHK-21
      cells, it was found that residues around the active site (W52, L53 and A149) of
      Lpro and others located elsewhere (K38, K39, R44, H138 and W159) are involved in
      the induction of eIF4G cleavage but not in the processing of the L/P1 junction.
      Modified viruses, encoding such amino acid substitutions within Lpro, can
      replicate in BHK-21 cells but did not grow well in primary bovine thyroid cells.
      This study characterizes mutant viruses that are deficient in blocking host cell
      responses to infection (e.g. interferon induction) and can assist in the rational
      design of antiviral agents targeting this process and in the production of
      attenuated viruses.

PMID- 28452294
TI  - Deltabaculoviruses encode a functional type I budded virus envelope fusion
      protein.
AB  - Envelope fusion proteins (F proteins) are major constituents of budded viruses
      (BVs) of alpha- and betabaculoviruses (Baculoviridae) and are essential for the
      systemic infection of insect larvae and insect cell culture. An f homologue gene
      is absent in gammabaculoviruses. Here we characterized the putative F-homologue
      (Cuni-F), encoded by (ORF) 104 of Culex nigripalpus nucleopolyhedrovirus
      (CuniNPV), the only deltabaculovirus member. When expressed alone, this protein
      seems to locate on the cell surface and is able to induce cell-cell fusion. When
      expressed by an alphabaculovirus (Autographa california nucleopolyhedrovirus), it
      was found to be incorporated into BVs. Western blot analyses detected the
      uncleaved Cuni-F0 and the furin-cleaved F1 forms. Treatment of infected cells
      with tunicamycin showed that Cuni-F contains N-glycans. Mutagenesis analysis
      identified the canonical furin cleavage site 126RARR129 as being responsible for
      the cleavage of Cuni-F in insect cells. The collective evidence suggests that
      CuniNPV encodes a functional F protein.

PMID- 28452295
TI  - ICTV Virus Taxonomy Profile: Secoviridae.
AB  - Members of the family Secoviridae are non-enveloped viruses with mono- or
      bipartite (RNA-1 and RNA-2) linear positive-sense ssRNA genomes with the size of
      the RNAs combined ranging from 9 to 13.7 kb. They are related to picornaviruses
      and are classified in the order Picornavirales. The majority of known members
      infect dicotyledonous plants and many are important plant pathogens (e.g.
      grapevine fanleaf virus and rice tungro spherical virus). This is a summary of
      the current International Committee on Taxonomy of Viruses (ICTV) report on the
      taxonomy of the family Secoviridae available at
      www.ictv.global/report/secoviridae.

PMID- 28452296
TI  - Forensic Approaches to Detect Possible Agents of Bioterror.
AB  - Many biological agents have been strategic pathogenic agents throughout history.
      Some have even changed history as a consequence of early discoveries of their use
      as weapons of war. Many of these bioagents can be easily isolated from the
      environment, and some have recently been genetically manipulated to become more
      pathogenic for biowarfare. However, it is difficult to determine accidental
      outbreaks of disease from intentional exposures. In this review, we examine how
      molecular tools have been used in combination with forensic research to resolve
      cases of unusual outbreaks and trace the source of the biocrime. New technologies
      are also discussed in terms of their crucial role impacting forensic science. The
      anthrax event of 2001 serves as an example of the real threat of bioterrorism and
      the employment of bioagents as weapons against a population. The Amerithrax
      investigation has given us lessons of the highest resolution possible with new
      technologies capable of distinguishing isolates at the base-pair level of
      sensitivity. In addition, we discuss the implications of proper sanitation to
      avoid waterborne diseases. The use of new methods in forensic science and health
      related surveillance will be invaluable in determining the source of any new
      disease outbreak, and these data will allow for a quick response to any type of
      public health threat, whether accidental or purposely initiated.

PMID- 28452321
TI  - Alimentary education.

PMID- 28452322
TI  - Global health humanities: defining an emerging field.

PMID- 28452323
TI  - Umberto Veronesi.

PMID- 28452324
TI  - Live better with Cancer.

PMID- 28452325
TI  - One week and a day.

PMID- 28452326
TI  - Resilient Women.

PMID- 28452327
TI  - One-step synthesis of luminescent YVO4:Eu3+/gamma-Al2O3 nanocomposites by spray
      pyrolysis.
AB  - Spray pyrolysis (SP) easily affords nano or sub-micro phosphor particles even on
      an industrial scale. However, control of the coordination environment around the
      emitting ion is inefficient, and the final solid matrix will dictate the symmetry
      of the emitter. Moreover, the fast heat treatment typical of SP usually results
      in heterogeneous symmetry sites. This paper aimed to obtain inorganic matrices
      incorporated with phosphors by SP while keeping the symmetry of the emitting ion
      unchanged along the pyrolysis process. Nanoparticles consisting of Eu3+-doped
      YVO4 phosphors with average diameter of 15 nm were prepared by the co
      precipitation method and were subsequently incorporated into the alumina matrix
      by SP, to yield YVO4:Eu3+/gamma-Al2O3 composite particles with mean size of 600
      nm. X-ray powder diffraction confirmed that the vanadate particles were
      incorporated into the alumina matrix, and that the gamma-Al2O3 phase emerged. The
      band due to the [Formula: see text] -> Eu3+ transition intensified as a
      consequence of the incorporation of YVO4:Eu3+ into alumina-the suppression
      effects caused by the surface properties of the YVO4:Eu3+ phosphor nanoparticles
      diminished, while the structure of Eu3+ remained unchanged in the matrix.

PMID- 28452328
TI  - A facile one-step strategy for development of a double network fibrous scaffold
      for nerve tissue engineering.
AB  - The aim of this study was to develop a novel double network scaffold composed of
      polycaprolactone fumarate (PCLF) and eggshell membrane (ESM) (ESM:PCLF) by using
      the vacuum infiltration method. Compared to ESM, the mechanical properties of
      double network scaffold were significantly improved, depending on the solvents
      applied for double network scaffold formation; acetic acid and dichloromethane.
      Noticeably, the toughness and strength of double network scaffold prepared using
      acetic acid were significantly improved compared to ESM (26.6 and 25 times,
      respectively) attributed to the existence of hydrophilic functional groups in
      acetic acid which made ESM flexible to absorb further PCLF solution. To assess
      the effect of double network formation on the biological behavior of ESM, the
      attachment, proliferation and spreading of PC12 cells cultured on the ESM:PCLF
      scaffolds were evaluated. Results revealed that the number of cells attached on
      double network ESM:PCLF scaffold were nearly similar to ESM and significantly
      higher than that of on the tissue culture plate (2.6 times) and PCLF film (1.7
      times). It is envisioned that the offered ESM:PCLF double network scaffold might
      have great potential to develop the constructs for nerve regeneration.

PMID- 28452329
TI  - Label-free SnO2 nanowire FET biosensor for protein detection.
AB  - Novel tin oxide field-effect-transistors (SnO2 NW-FET) for pH and protein
      detection applicable in the healthcare sector are reported. With a SnO2 NW-FET
      the proof-of-concept of a bio-sensing device is demonstrated using the carrier
      transport control of the FET channel by a (bio-) liquid modulated gate. Ultra
      thin Al2O3 fabricated by a low temperature atomic layer deposition (ALD) process
      represents a sensitive layer to H+ ions safeguarding the nanowire at the same
      time. Successful pH sensitivity is demonstrated for pH ranging from 3 to 10. For
      protein detection, the SnO2 NW-FET is functionalized with a receptor molecule
      which specifically interacts with the protein of interest to be detected. The
      feasibility of this approach is demonstrated via the detection of a biotinylated
      protein using a NW-FET functionalized with streptavidin. An immediate label-free
      electronic read-out of the signal is shown. The well-established Enzyme-Linked
      Immunosorbent Assay (ELISA) method is used to determine the optimal experimental
      procedure which would enable molecular binding events to occur while being
      compatible with a final label-free electronic read-out on a NW-FET. Integration
      of the bottom-up fabricated SnO2 NW-FET pH- and biosensor into a microfluidic
      system (lab-on-a-chip) allows the automated analysis of small volumes in the 400
      MUl range as would be desired in portable on-site point-of-care (POC) devices for
      medical diagnosis.

PMID- 28452330
TI  - Synthesis and magnetic properties of cobalt-iron/cobalt-ferrite soft/hard
      magnetic core/shell nanowires.
AB  - A straightforward method for the synthesis of CoFe2.7/CoFe2O4 core/shell
      nanowires is described. The proposed method starts with a conventional pulsed
      electrodeposition procedure on alumina nanoporous template. The obtained CoFe2.7
      nanowires are released from the template and allowed to oxidize at room
      conditions over several weeks. The effects of partial oxidation on the structural
      and magnetic properties were studied by x-ray spectrometry, magnetometry, and
      scanning and transmission electron microscopy. The results indicate that the
      final nanowires are composed of 5 nm iron-cobalt alloy nanoparticles. Releasing
      the nanowires at room conditions promoted surface oxidation of the nanoparticles
      and created a CoFe2O4 shell spinel-like structure. The shell avoids internal
      oxidation and promotes the formation of bi-magnetic soft/hard magnetic core/shell
      nanowires. The magnetic properties of both the initial single-phase CoFe2.7
      nanowires and the final core/shell nanowires, reveal that the changes in the
      properties from the array are due to the oxidation more than effects associated
      with released processes (disorder and agglomeration).

PMID- 28452331
TI  - Design and manufacturing challenges of optogenetic neural interfaces: a review.
AB  - : Optogenetics is a relatively new technology to achieve cell-type specific
      neuromodulation with millisecond-scale temporal precision. Optogenetic tools are
      being developed to address neuroscience challenges, and to improve the knowledge
      about brain networks, with the ultimate aim of catalyzing new treatments for
      brain disorders and diseases. To reach this ambitious goal the implementation of
      mature and reliable engineered tools is required. The success of optogenetics
      relies on optical tools that can deliver light into the neural tissue.
      Objective/Approach: Here, the design and manufacturing approaches available to
      the scientific community are reviewed, and current challenges to accomplish
      appropriate scalable, multimodal and wireless optical devices are discussed.
      SIGNIFICANCE: Overall, this review aims at presenting a helpful guidance to the
      engineering and design of optical microsystems for optogenetic applications.

PMID- 28452333
TI  - A water-soluble rhodamine B-derived fluorescent probe for pH monitoring and
      imaging in acidic regions.
AB  - A structurally simple, water-soluble rhodamine-derivatived fluorescent probe,
      which is responsive to acidic pH, was conveniently synthesized via a one-step
      condensation reaction of rhodamine B hydrazide and 4-formybenzene-1,3
      disulfonate. As a stable and highly sensitive pH sensor, the probe displays an
      approximately 50-fold fluorescence enhancement over the pH range of 7.16-4.89 as
      the structure of probe changes from spirocyclic (weak fluorescent) to ring-open
      (strong fluorescent) with decreasing pH. The synthesized fluorescent probe is
      applied to the detection of pH changes in vitro and in vivo bioimaging of
      immortalized gastric cancer cells, with satisfactory results.

PMID- 28452332
TI  - Function and mechanism of mesoporous bioactive glass adsorbed epidermal growth
      factor for accelerating bone tissue regeneration.
AB  - Mesoporous bioactive glass (MBG) has been demonstrated to play a vital role in
      bone tissue engineering due to its bioactivity, biocompatibility, and
      osteoinduction properties. Here, we report that MBG grafted with an amino group
      (MBG-NH2) and MBG-NH2 adsorbed epidermal growth factor (EGF) (MBG-NH2/EGF)
      sustained-release EGF, and MBG-NH2/EGF could accelerate osteoblast
      differentiation and mineralization in MC3T3-E1 cells. We found that MBG-NH2 could
      promote bone-like deposit formation and Ca deposition in vitro. Intriguingly, we
      observed that MBG-NH2/EGF enhanced MC3T3-E1 cell adhesion. We also showed that
      extracellular signal-regulated kinase 1/2 (ERK1/2) was phosphorylated when MC3T3
      E1 cells were cultured on MBG-NH2/EGF. Interestingly, the transcription factor
      Runx2, important for osteoblast differentiation, was also activated when MC3T3-E1
      cells were cultured on MBG-NH2/EGF. We showed that MC3T3-E1 cells cultured on MBG
      NH2/EGF activating Runx2 was through ERK1/2 phosphorylation. Consistent with this
      survey, we observed that MC3T3-E1 cells cultured on MBG-NH2/EGF accelerated
      osteoblastic marker gene expressions, including osteopontin (Opn) and osteocalcin
      (Ocn). Taken together, we conclude that the osteoblast differentiation and
      mineralization were accelerated in MC3T3-E1 cells cultured on MBG-NH2/EGF through
      ERK-activated Runx2 pathway. These findings support the idea that MBG-NH2/EGF is
      a potential biomaterial for bone tissue repair in bone defect-related diseases.

PMID- 28452334
TI  - Dosimetric effect of internal metallic ports in temporary tissue expanders on
      postmastectomy radiation therapy: a Monte Carlo study.
AB  - To investigate the dosimetric effect of the internal metallic port (IMP) in a
      tissue expander (TE) on the dose distribution of postmastectomy radiation therapy
      (PMRT). A total of 10 patients who have received PMRT with a TE were selected
      retrospectively. For each patient, the dose distributions of treatment plans with
      a 10 MV photon beam were calculated using the Monte Carlo (MC) method with CT
      images. The dose distributions without the TE were also calculated by designating
      the mass densities of the TE including the IMP as those of tissue. From the MC
      calculations, the dose-volumetric parameters were calculated and analyzed for
      several structures: the planning target volume (PTV) including the TE, the PTV
      excluding the TE (PTVreal), the TE alone, heart, and lungs. For the PTV and
      PTVreal, dose-volumetric parameters did not appear to depend on the IMP. Within
      the TE volume, the maximum dose and D 1% were higher with the IMP than without
      the IMP (62.8  +/-  1.4 Gy versus 57.9  +/-  1.3 Gy with p  <  0.001 and 58.6  +/
      1.6 Gy versus 57.0  +/-  1.2 Gy with p  =  0.035). The values of V 100% and V
      95% were lower with the IMP than without the IMP (77.9%  +/-  7.6% versus 87.2% 
      +/-  5.3% with p  =  0.008 and 89.5%  +/-  5.6% versus 94.6%  +/-  2.9% with p  =
      0.027). The IMP did not affect dose-volumetric parameters of heart and lungs.
      Dosimetric changes due to the IMP occurred mainly within the TE, and not in the
      target volume, heart, and lungs.

PMID- 28452335
TI  - Performance of laser sintered Ti-6Al-4V implants with bone-inspired porosity and
      micro/nanoscale surface roughness in the rabbit femur.
AB  - Long term success of bone-interfacing implants remains a challenge in compromised
      patients and in areas of low bone quality. While surface roughness at the
      micro/nanoscale can promote osteogenesis, macro-scale porosity is important for
      promoting mechanical stability of the implant over time. Currently, machining
      techniques permit pores to be placed throughout the implant, but the pores are
      generally uniform in dimension. The advent of laser sintering provides a way to
      design and manufacture implants with specific porosity and variable dimensions at
      high resolution. This approach enables production of metal implants that mimic
      complex geometries found in biology. In this study, we used a rabbit femur model
      to compare osseointegration of laser sintered solid and porous implants. Ti-6Al
      4V implants were laser sintered in a clinically relevant size and shape. One set
      of implants had a novel porosity based on human trabecular bone; both sets had
      grit-blasted/acid-etched surfaces. After characterization, implants were inserted
      transaxially into rabbit femora; mechanical testing, micro-computed tomography
      (microCT) and histomorphometry were conducted 10 weeks post-operatively. There
      were no differences in pull-out strength or bone-to-implant contact. However,
      both microCT and histomorphometry showed significantly higher new bone volume for
      porous compared to solid implants. Bone growth was observed into porous implant
      pores, especially near apical portions of the implant interfacing with cortical
      bone. These results show that laser sintered Ti-6Al-4V implants with
      micro/nanoscale surface roughness and trabecular bone-inspired porosity promote
      bone growth and may be used as a superior alternative to solid implants for bone
      interfacing implants.

PMID- 28452336
TI  - Numerical and experimental study of radiation induced conductivity change of
      carbon nanotube filled polymers.
AB  - Measuring the conductivity changes of sensing materials to detect a wide range of
      radiation energy and dosage is one of the major sensing mechanisms of radiation
      sensors. Carbon nanotube (CNT) filled composites are suitable for sensing
      radiation because of the extraordinary electrical properties of CNTs and the CNT
      network formed inside the polymer matrix. Although the use of CNT-based
      nanocomposites as potential radiation sensing materials has been widely studied,
      there is still a lack of theoretical models to analyze the relationship between
      electrical conductivity and radiation dosages. In this article, we propose a 3D
      model to describe the electrical conductivity of CNT-based nanocomposites when
      being irradiated by ionizing radiation. The Monte Carlo method has been employed
      to calculate radiation intensity, CNT concentration and alignment's influence on
      the electrical conductivity. Our simulation shows a better agreement when CNT
      loading is between the percolation threshold and 3% volume fraction. Radiation
      experiments have been performed to verify the reliability of our model to
      illustrate a power function relationship between the electrical conductivity of a
      CNT-filled polymer and radiation intensity. In addition, the predicted alignment
      to obtain the best sensitivity for radiation sensing has been discussed to help
      with CNT-network building in the fabrication process.

PMID- 28452337
TI  - Calculation of the time resolution of the J-PET tomograph using kernel density
      estimation.
AB  - In this paper we estimate the time resolution of the J-PET scanner built from
      plastic scintillators. We incorporate the method of signal processing using the
      Tikhonov regularization framework and the kernel density estimation method. We
      obtain simple, closed-form analytical formulae for time resolution. The proposed
      method is validated using signals registered by means of the single detection
      unit of the J-PET tomograph built from a 30 cm long plastic scintillator strip.
      It is shown that the experimental and theoretical results obtained for the J-PET
      scanner equipped with vacuum tube photomultipliers are consistent.

PMID- 28452338
TI  - Recent advances in physiological oscillations.

PMID- 28452339
TI  - Advanced optical simulation of scintillation detectors in GATE V8.0: first
      implementation of a reflectance model based on measured data.
AB  - Typical PET detectors are composed of a scintillator coupled to a photodetector
      that detects scintillation photons produced when high energy gamma photons
      interact with the crystal. A critical performance factor is the collection
      efficiency of these scintillation photons, which can be optimized through
      simulation. Accurate modelling of photon interactions with crystal surfaces is
      essential in optical simulations, but the existing UNIFIED model in GATE is often
      inaccurate, especially for rough surfaces. Previously a new approach for
      modelling surface reflections based on measured surfaces was validated using
      custom Monte Carlo code. In this work, the LUT Davis model is implemented and
      validated in GATE and GEANT4, and is made accessible for all users in the nuclear
      imaging research community. Look-up-tables (LUTs) from various crystal surfaces
      are calculated based on measured surfaces obtained by atomic force microscopy.
      The LUTs include photon reflection probabilities and directions depending on
      incidence angle. We provide LUTs for rough and polished surfaces with different
      reflectors and coupling media. Validation parameters include light output
      measured at different depths of interaction in the crystal and photon track
      lengths, as both parameters are strongly dependent on reflector characteristics
      and distinguish between models. Results from the GATE/GEANT4 beta version are
      compared to those from our custom code and experimental data, as well as the
      UNIFIED model. GATE simulations with the LUT Davis model show average variations
      in light output of  <2% from the custom code and excellent agreement for track
      lengths with R 2  >  0.99. Experimental data agree within 9% for relative light
      output. The new model also simplifies surface definition, as no complex input
      parameters are needed. The LUT Davis model makes optical simulations for nuclear
      imaging detectors much more precise, especially for studies with rough crystal
      surfaces. It will be available in GATE V8.0.

PMID- 28452340
TI  - Structure of rare-earth chalcogenide glasses by neutron and x-ray diffraction.
AB  - The method of neutron diffraction with isomorphic substitution was used to
      measure the structure of the rare-earth chalcogenide glasses [Formula: see
      text](Ga2 X 3)0.33(GeX 2)0.60 with [Formula: see text] or Ce and [Formula: see
      text] or Se. X-ray diffraction was also used to measure the structure of the
      sulphide glass. The results are consistent with networks that are built from GeX
      4 and GaX 4 tetrahedra, and give R-S and R-Se coordination numbers of 8.0(2) and
      8.5(4), respectively. The minimum nearest-neighbour R-R distance associated with
      rare-earth clustering is discussed.

PMID- 28452341
TI  - Reference dosimetry of proton pencil beams based on dose-area product: a proof of
      concept.
AB  - This paper describes a novel approach to the reference dosimetry of proton pencil
      beams based on dose-area product ([Formula: see text]). It depicts the
      calibration of a large-diameter plane-parallel ionization chamber in terms of
      dose-area product in a 60Co beam, the Monte Carlo calculation of beam quality
      correction factors-in terms of dose-area product-in proton beams, the Monte Carlo
      calculation of nuclear halo correction factors, and the experimental
      determination of [Formula: see text] of a single proton pencil beam. This new
      approach to reference dosimetry proves to be feasible, as it yields [Formula: see
      text] values in agreement with the standard and well-established approach of
      determining the absorbed dose to water at the centre of a broad homogeneous field
      generated by the superposition of regularly-spaced proton pencil beams.

PMID- 28452342
TI  - Air kerma calculation in Monte Carlo simulations for deriving normalized
      glandular dose coefficients in mammography.
AB  - The estimation of the mean glandular dose in mammography using Monte Carlo
      simulations requires the calculation of the incident air kerma evaluated on the
      breast surface. In such a calculation, caution should be applied in considering
      explicitly the presence of the top compression paddle, since Compton scattering
      in this slab may produce a large spread of the incidence angles of x-ray photons
      on the scoring surface. Then, the calculation of the incident air kerma should
      contain the 'effective' area of the scoring surface, which takes into account the
      angle of incidence of photons on such a surface. Using Geant4 Monte Carlo
      simulations with a code previously validated according to the Task Group 195 of
      the American Association of Physicists in Medicine, we show that for typical x
      ray spectra and energy range adopted in mammography, the resulting discrepancy in
      the calculation of the incident air kerma may lead to an overestimation from a
      minimum of 10% up to 12% of normalized dose coefficients and, hence, of the
      corresponding mean glandular dose if this contribution is not considered.

PMID- 28452343
TI  - Charge optimized many body (COMB) potentials for Pt and Au.
AB  - Interatomic potentials for Pt and Au are developed within the third generation
      charge optimized many-body (COMB3) formalism. The potentials are capable of
      reproducing phase order, lattice constants, and elastic constants of Pt and Au
      systems as experimentally measured or calculated by density functional theory. We
      also fit defect formation energies, surface energies and stacking fault energies
      for Pt and Au metals. The resulting potentials are used to map a 2D contour of
      the gamma surface and simulate the tensile test of 16-grain polycrystalline Pt
      and Au structures at 300 K. The stress-strain behaviour is investigated and the
      primary slip systems {1 1 1}<1 [Formula: see text] 0> are identified. In
      addition, we perform high temperature (1800 K for Au and 2300 K for Pt) molecular
      dynamics simulations of 30 nm Pt and Au truncated octahedron nanoparticles and
      examine morphological changes of each particle. We further calculate the
      activation energy barrier for surface diffusion during simulations of several
      nanoseconds and report energies of [Formula: see text] eV for Pt and [Formula:
      see text] eV for Au. This initial parameterization and application of the Pt and
      Au potentials demonstrates a starting point for the extension of these potentials
      to multicomponent systems within the COMB3 framework.

PMID- 28452344
TI  - Clonal analysis reveals remarkable functional heterogeneity during hematopoietic
      stem cell emergence.

PMID- 28452346
TI  - Method and Mechanisms of Soil Stabilization Using Electric Arc Furnace Dust.
AB  - This paper reports the method and mechanism for improving the strength of marl
      and desert sand utilizing electric arc furnace dust (EAFD), an industrial by
      product, in lieu of cement or lime. EAFD was used in conjunction with a small
      quantity (2%) of cement. The mechanical properties and durability characteristics
      of marl and sand mixed with 2% cement plus 5-, 10-, 20- or 30%-EAFD, by weight of
      the soil, were evaluated. The soil-cement-EAFD mixtures were used to determine
      their unconfined compressive strength (UCS), soaked California Bearing Ratio
      (CBR) and durability. The risk of leaching of toxic heavy metals, such as lead
      and cadmium, from the stabilized soils to the groundwater was also investigated.
      The mechanisms of stabilization of the selected soils due to the use of EAFD
      along with a small quantity of cement are also elucidated. The usage of 20 to 30%
      EAFD with 2% cement was noted to considerably improve the mechanical properties
      and durability of both marl and sand.

PMID- 28452347
TI  - Segregation of liquid crystal mixtures in topological defects.
AB  - The structure and physical properties of liquid crystal (LC) mixtures are a
      function of composition, and small changes can have pronounced effects on
      observables, such as phase-transition temperatures. Traditionally, LC mixtures
      have been assumed to be compositionally homogenous. The results of chemically
      detailed simulations presented here show that this is not the case; pronounced
      deviations of the local order from that observed in the bulk at defects and
      interfaces lead to significant compositional segregation effects. More
      specifically, two disclination lines are stabilized in this work by introducing
      into a nematic liquid crystal mixture a cylindrical body that exhibits
      perpendicular anchoring. It is found that the local composition deviates
      considerably from that of the bulk at the interface with the cylinder and in the
      defects, thereby suggesting new assembly and synthetic strategies that may
      capitalize on the unusual molecular environment provided by liquid crystal
      mixtures.

PMID- 28452345
TI  - HMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment
      and Paneth cell niche.
AB  - High-mobility group A1 (Hmga1) chromatin remodelling proteins are enriched in
      intestinal stem cells (ISCs), although their function in this setting was
      unknown. Prior studies showed that Hmga1 drives hyperproliferation, aberrant
      crypt formation and polyposis in transgenic mice. Here we demonstrate that Hmga1
      amplifies Wnt/beta-catenin signalling to enhance self-renewal and expand the ISC
      compartment. Hmga1 upregulates genes encoding both Wnt agonist receptors and
      downstream Wnt effectors. Hmga1 also helps to 'build' an ISC niche by expanding
      the Paneth cell compartment and directly inducing Sox9, which is required for
      Paneth cell differentiation. In human intestine, HMGA1 and SOX9 are positively
      correlated, and both become upregulated in colorectal cancer. Our results define
      a unique role for Hmga1 in intestinal homeostasis by maintaining the stem cell
      pool and fostering terminal differentiation to establish an epithelial stem cell
      niche. This work also suggests that deregulated Hmga1 perturbs this equilibrium
      during intestinal carcinogenesis.

PMID- 28452350
TI  - Multiple sclerosis: Perinatal risk factors for paediatric MS.

PMID- 28452348
TI  - WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic
      interventions.
AB  - There has been significant progress in understanding the role of
      neurotransmitters in normal and pathologic brain function. However, preclinical
      trials aimed at improving therapeutic interventions do not take advantage of real
      time in vivo neurochemical changes in dynamic brain processes such as disease
      progression and response to pharmacologic, cognitive, behavioral, and
      neuromodulation therapies. This is due in part to a lack of flexible research
      tools that allow in vivo measurement of the dynamic changes in brain chemistry.
      Here, we present a research platform, WINCS Harmoni, which can measure in vivo
      neurochemical activity simultaneously across multiple anatomical targets to study
      normal and pathologic brain function. In addition, WINCS Harmoni can provide real
      time neurochemical feedback for closed-loop control of neurochemical levels via
      its synchronized stimulation and neurochemical sensing capabilities. We
      demonstrate these and other key features of this platform in non-human primate,
      swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems
      like the one described here will improve our understanding of the dynamics of
      brain physiology in the context of neurologic disease and therapeutic
      interventions, which may lead to the development of precision medicine and
      personalized therapies for optimal therapeutic efficacy.

PMID- 28452349
TI  - Wheat Ms2 encodes for an orphan protein that confers male sterility in grass
      species.
AB  - Male sterility is a valuable trait for plant breeding and hybrid seed production.
      The dominant male-sterile gene Ms2 in common wheat has facilitated the release of
      hundreds of breeding lines and cultivars in China. Here, we describe the map
      based cloning of the Ms2 gene and show that Ms2 confers male sterility in wheat,
      barley and Brachypodium. MS2 appears as an orphan gene within the Triticinae and
      expression of Ms2 in anthers is associated with insertion of a retroelement into
      the promoter. The cloning of Ms2 has substantial potential to assemble practical
      pipelines for recurrent selection and hybrid seed production in wheat.

PMID- 28452351
TI  - Motor neuron disease: Detection of glycine-proline repeat protein offers new
      biomarker in patients with C9orf72 expansion.

PMID- 28452352
TI  - Parkinson disease: Antibodies reveal age of Lewy pathology in PD.

PMID- 28452353
TI  - Alzheimer disease: A quantitative trait approach to GWAS pays dividends.

PMID- 28452354
TI  - Stroke: Cortical superficial siderosis absent in CADASIL.

PMID- 28452356
TI  - Corrigendum: Very rapid long-distance sea crossing by a migratory bird.

PMID- 28452355
TI  - Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural
      basis for cytidine deamination and specificity.
AB  - Nucleic acid editing enzymes are essential components of the immune system that
      lethally mutate viral pathogens and somatically mutate immunoglobulins, and
      contribute to the diversification and lethality of cancers. Among these enzymes
      are the seven human APOBEC3 deoxycytidine deaminases, each with unique target
      sequence specificity and subcellular localization. While the enzymology and
      biological consequences have been extensively studied, the mechanism by which
      APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal
      structure of a complex of a cytidine deaminase with ssDNA bound in the active
      site at 2.2 A. This structure not only visualizes the active site poised for
      catalysis of APOBEC3A, but pinpoints the residues that confer specificity towards
      CC/TC motifs. The APOBEC3A-ssDNA complex defines the 5'-3' directionality and
      subtle conformational changes that clench the ssDNA within the binding groove,
      revealing the architecture and mechanism of ssDNA recognition that is likely
      conserved among all polynucleotide deaminases, thereby opening the door for the
      design of mechanistic-based therapeutics.

PMID- 28452357
TI  - Solid-state synthesis of ordered mesoporous carbon catalysts via a
      mechanochemical assembly through coordination cross-linking.
AB  - Ordered mesoporous carbons (OMCs) have demonstrated great potential in catalysis,
      and as supercapacitors and adsorbents. Since the introduction of the organic
      organic self-assembly approach in 2004/2005 until now, the direct synthesis of
      OMCs is still limited to the wet processing of phenol-formaldehyde
      polycondensation, which involves soluble toxic precursors, and acid or alkali
      catalysts, and requires multiple synthesis steps, thus restricting the widespread
      application of OMCs. Herein, we report a simple, general, scalable and
      sustainable solid-state synthesis of OMCs and nickel OMCs with uniform and
      tunable mesopores (~4-10 nm), large pore volumes (up to 0.96 cm3 g-1) and high
      surface areas exceeding 1,000 m2 g-1, based on a mechanochemical assembly between
      polyphenol-metal complexes and triblock co-polymers. Nickel nanoparticles (~5.40
      nm) confined in the cylindrical nanochannels show great thermal stability at 600 
      degrees C. Moreover, the nickel OMCs offer exceptional activity in the
      hydrogenation of bulky molecules (~2 nm).

PMID- 28452359
TI  - Corrigendum: Harnessing Nature's Diversity: Discovering organophosphate
      bioscavenger characteristics among low molecular weight proteins.

PMID- 28452358
TI  - Antibiotic-producing symbionts dynamically transition between plant pathogenicity
      and insect-defensive mutualism.
AB  - Pathogenic and mutualistic bacteria associated with eukaryotic hosts often lack
      distinctive genomic features, suggesting regular transitions between these
      lifestyles. Here we present evidence supporting a dynamic transition from plant
      pathogenicity to insect-defensive mutualism in symbiotic Burkholderia gladioli
      bacteria. In a group of herbivorous beetles, these symbionts protect the
      vulnerable egg stage against detrimental microbes. The production of a blend of
      antibiotics by B. gladioli, including toxoflavin, caryoynencin and two new
      antimicrobial compounds, the macrolide lagriene and the isothiocyanate
      sinapigladioside, likely mediate this defensive role. In addition to vertical
      transmission, these insect symbionts can be exchanged via the host plant and
      retain the ability to initiate systemic plant infection at the expense of the
      plant's fitness. Our findings provide a paradigm for the transition between
      pathogenic and mutualistic lifestyles and shed light on the evolution and
      chemical ecology of this defensive mutualism.

PMID- 28452360
TI  - An intermolecular FRET sensor detects the dynamics of T cell receptor clustering.
AB  - Clustering of the T-cell receptor (TCR) is thought to initiate downstream
      signalling. However, the detection of protein clustering with high spatial and
      temporal resolution remains challenging. Here we establish a Forster resonance
      energy transfer (FRET) sensor, named CliF, which reports intermolecular
      associations of neighbouring proteins in live cells. A key advantage of the
      single-chain FRET sensor is that it can be combined with image correlation
      spectroscopy (ICS), single-particle tracking (SPT) and fluorescence lifetime
      imaging microscopy (FLIM). We test the sensor with a light-sensitive actuator
      that induces protein aggregation upon radiation with blue light. When applied to
      T cells, the sensor reveals that TCR triggering increases the number of dense TCR
      CD3 clusters. Further, we find a correlation between cluster movement within the
      immunological synapse and cluster density. In conclusion, we develop a sensor
      that allows us to map the dynamics of protein clustering in live T cells.

PMID- 28452362
TI  - Erratum: High affinity anchoring of the decoration protein pb10 onto the
      bacteriophage T5 capsid.

PMID- 28452361
TI  - Elevated levels of Bcl-3 inhibits Treg development and function resulting in
      spontaneous colitis.
AB  - Bcl-3 is an atypical NF-kappaB family member that regulates NF-kappaB-dependent
      gene expression in effector T cells, but a cell-intrinsic function in regulatory
      T (Treg) cells and colitis is not clear. Here we show that Bcl-3 expression
      levels in colonic T cells correlate with disease manifestation in patients with
      inflammatory bowel disease. Mice with T-cell-specific overexpression of Bcl-3
      develop severe colitis that can be attributed to defective Treg cell development
      and function, leading to the infiltration of immune cells such as pro
      inflammatory gammadeltaT cells, but not alphabeta T cells. In Treg cells, Bcl-3
      associates directly with NF-kappaB p50 to inhibit DNA binding of p50/p50 and
      p50/p65 NF-kappaB dimers, thereby regulating NF-kappaB-mediated gene expression.
      This study thus reveals intrinsic functions of Bcl-3 in Treg cells, identifies
      Bcl-3 as a potential prognostic marker for colitis and illustrates the mechanism
      by which Bcl-3 regulates NF-kappaB activity in Tregs to prevent colitis.

PMID- 28452364
TI  - Corrigendum: Characterization of a novel N-acetylneuraminic acid lyase favoring
      industrial N-acetylneuraminic acid synthesis process.

PMID- 28452363
TI  - Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on
      native protein from lysate.
AB  - The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a
      critical role in signal transduction by activating Ras. Here we introduce a
      single-molecule assay in which individual SOS molecules are captured from raw
      cell lysate using Ras-functionalized supported membrane microarrays. This enables
      characterization of the full-length SOS protein, which has not previously been
      studied in reconstitution due to difficulties in purification. Our measurements
      on the full-length protein reveal a distinct role of the C-terminal proline-rich
      (PR) domain to obstruct the engagement of allosteric Ras independently of the
      well-known N-terminal domain autoinhibition. This inhibitory role of the PR
      domain limits Grb2-independent recruitment of SOS to the membrane through binding
      of Ras.GTP in the SOS allosteric binding site. More generally, this assay
      strategy enables characterization of the functional behaviour of GEFs with single
      molecule precision but without the need for purification.

PMID- 28452365
TI  - Pluronic based beta-cyclodextrin polyrotaxanes for treatment of Niemann-Pick Type
      C disease.
AB  - Niemann-Pick Type C disease (NPC) is a rare metabolic disorder characterized by
      disruption of normal cholesterol trafficking within the cells of the body. There
      are no FDA approved treatments available for NPC patients. Recently, the
      cycloheptaglucoside 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) has shown
      efficacy as a potential NPC therapeutic by extending lifetime in NPC mice,
      delaying neurodegeneration, and decreasing visceral and neurological cholesterol
      burden. Although promising, systemic HP-beta-CD treatment is limited by a
      pharmacokinetic profile characterized by rapid loss through renal filtration. To
      address these shortcomings, we sought to design a family of HP-beta-CD pro-drug
      delivery vehicles, known as polyrotaxanes (PR), capable of increasing the
      efficacy of a given injected dose by improving both pharmacokinetic profile and
      bioavailability of the HP-beta-CD agent. PR can effectively diminish the
      cholesterol pool within the liver, spleen, and kidney at molar concentrations 10
      to-100-fold lower than monomeric HP-beta-CD. In addition to this proof-of
      concept, use of PR scaffolds with differing physiochemical properties reveal
      structure-activity relationships in which PR characteristics, including
      hydrophobicity, threading efficiency and surface charge, were found to both
      decisively and subtly effect therapeutic efficacy. PR scaffolds exhibit
      absorption, pharmacokinetics, and biodistribution patterns that are significantly
      altered from monomeric HP-beta-CD. In all, PR scaffolds hold great promise as
      potential treatments for visceral disease in NPC patients.

PMID- 28452366
TI  - The inheritance of a Mesozoic landscape in western Scandinavia.
AB  - In-situ weathered bedrock, saprolite, is locally found in Scandinavia, where it
      is commonly thought to represent pre-Pleistocene weathering possibly associated
      with landscape formation. The age of weathering, however, remains loosely
      constrained, which has an impact on existing geological and landscape evolution
      models and morphotectonic correlations. Here we provide new geochronological
      evidence that some of the low-altitude basement landforms on- and offshore
      southwestern Scandinavia are a rejuvenated geomorphological relic from Mesozoic
      times. K-Ar dating of authigenic, syn-weathering illite from saprolitic remnants
      constrains original basement exposure in the Late Triassic (221.3+/-7.0-206.2+/
      4.2 Ma) through deep weathering in a warm climate and subsequent partial
      mobilization of the saprolitic mantle into the overlying sediment cascade system.
      The data support the bulk geomorphological development of west Scandinavia
      coastal basement rocks during the Mesozoic and later, long-lasting relative
      tectonic stability. Pleistocene glaciations played an additional geomorphological
      role, selectively stripping the landscape from the Mesozoic overburden and
      carving glacial landforms down to Plio-Pleistocene times. Saprolite K-Ar dating
      offers unprecedented possibilities to study past weathering and landscape
      evolution processes.

PMID- 28452367
TI  - Homogeneously catalysed conversion of aqueous formaldehyde to H2 and carbonate.
AB  - Small organic molecules provide a promising solution for the requirement to store
      large amounts of hydrogen in a future hydrogen-based energy system. Herein, we
      report that diolefin-ruthenium complexes containing the chemically and redox non
      innocent ligand trop2dad catalyse the production of H2 from formaldehyde and
      water in the presence of a base. The process involves the catalytic conversion to
      carbonate salt using aqueous solutions and is the fastest reported for
      acceptorless formalin dehydrogenation to date. A mechanism supported by density
      functional theory calculations postulates protonation of a ruthenium hydride to
      form a low-valent active species, the reversible uptake of dihydrogen by the
      ligand and active participation of both the ligand and the metal in substrate
      activation and dihydrogen bond formation.

PMID- 28452369
TI  - Corrigendum: Mechanistic stratification in electroactive biofilms of Geobacter
      sulfurreducens mediated by pilus nanowires.

PMID- 28452370
TI  - Observability of Boolean multiplex control networks.
AB  - Boolean multiplex (multilevel) networks (BMNs) are currently receiving
      considerable attention as theoretical arguments for modeling of biological
      systems and system level analysis. Studying control-related problems in BMNs may
      not only provide new views into the intrinsic control in complex biological
      systems, but also enable us to develop a method for manipulating biological
      systems using exogenous inputs. In this article, the observability of the Boolean
      multiplex control networks (BMCNs) are studied. First, the dynamical model and
      structure of BMCNs with control inputs and outputs are constructed. By using of
      Semi-Tensor Product (STP) approach, the logical dynamics of BMCNs is converted
      into an equivalent algebraic representation. Then, the observability of the BMCNs
      with two different kinds of control inputs is investigated by giving necessary
      and sufficient conditions. Finally, examples are given to illustrate the
      efficiency of the obtained theoretical results.

PMID- 28452368
TI  - Activin A more prominently regulates muscle mass in primates than does GDF8.
AB  - Growth and differentiation factor 8 (GDF8) is a TGF-beta superfamily member, and
      negative regulator of skeletal muscle mass. GDF8 inhibition results in prominent
      muscle growth in mice, but less impressive hypertrophy in primates, including
      man. Broad TGF-beta inhibition suggests another family member negatively
      regulates muscle mass, and its blockade enhances muscle growth seen with GDF8
      specific inhibition. Here we show that activin A is the long-sought second
      negative muscle regulator. Activin A specific inhibition, on top of GDF8
      inhibition, leads to pronounced muscle hypertrophy and force production in mice
      and monkeys. Inhibition of these two ligands mimics the hypertrophy seen with
      broad TGF-beta blockers, while avoiding the adverse effects due to inhibition of
      multiple family members. Altogether, we identify activin A as a second negative
      regulator of muscle mass, and suggest that inhibition of both ligands provides a
      preferred therapeutic approach, which maximizes the benefit:risk ratio for muscle
      diseases in man.

PMID- 28452371
TI  - Differential processing of small RNAs during endoplasmic reticulum stress.
AB  - The accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen
      due to the disruption of the homeostatic system of the ER leads to the induction
      of the ER stress response. Cellular stress-induced pathways globally transform
      genes expression on both the transcriptional and post-transcriptional levels with
      small RNA involvement as regulators of the stress response. The modulation of
      small RNA processing might represent an additional layer of a complex stress
      response program. However, it is poorly understood. Here, we studied changes in
      expression and small RNAs processing upon ER stress in Jurkat T-cells. Induced by
      ER-stress, depletion of miRNAs among small RNA composition was accompanied by a
      global decrease of 3' mono-adenylated, mono-cytodinylated and a global increase
      of 3' mono-uridinylated miRNA isoforms. We observed the specific subset of
      differentially expressed microRNAs, and also the dramatic induction of 32-nt tRNA
      fragments precisely phased to 5' and 3' ends of tRNA from a subset of tRNA
      isotypes. The induction of these tRNA fragments was linked to Angiogenin RNase,
      which mediates translation inhibition. Overall, the global perturbations of the
      expression and processing of miRNAs and tiRNAs were the most prominent features
      of small RNA transcriptome changes upon ER stress.

PMID- 28452374
TI  - Prognostic significance of huntingtin interacting protein 1 expression on
      patients with acute myeloid leukemia.
AB  - Huntingtin interacting protein 1 (HIP1) is an endocytic protein which is
      overexpressed in a variety of human cancers and involved in cancer-causing
      translocation in leukemia. However, the prognostic impact of HIP1 expression on
      AML remains unclear. In this study, quantification of HIP1 transcript by real
      time quantitative PCR in bone marrow blasts was performed in 270 AML patients. As
      a result, high HIP1 expression was seen more frequently in older patients, M4/M5
      morphology and genes of NPM1 and DNMT3A mutations, and underrepresented in
      favorable karyotype subgroups and CEBPA double allele mutations in our AML
      patients. We also found high HIP1 expressers showed lower levels of hemoglobin.
      In addition, overexpression of HIP1 was associated with an inferior overall
      survival. The prognostic value of HIP1 expression was validated in patients from
      an independent TCGA cohort. Notably, up-regulation of miR-16, miR-15a, miR-28 and
      miR-660 were seen in high HIP1 expressers from the two independent cohorts. In
      vitro, interfereing of HIP1 expression by siRNA suppressed the proliferation of
      leukemic cells, and downregulation of these miRNAs were seen in THP-1 and Kasumi
      cell lines after silencing HIP1 expression. In conclusion, the HIP1 gene
      expression might serve as a reliable predictor for overall survival in AML
      patients.

PMID- 28452373
TI  - Endometrial cancer gene panels: clinical diagnostic vs research germline DNA
      testing.
AB  - Endometrial cancer is the most common gynecological cancer, but is nevertheless
      uncommon enough to have value as a signature cancer for some hereditary cancer
      syndromes. Commercial multigene testing panels include up to 13 different genes
      annotated for germline DNA testing of patients with endometrial cancer. Many
      other genes have been reported as relevant to familial endometrial cancer from
      directed genome-wide sequencing studies or multigene panel testing, or research.
      This review assesses the evidence supporting association with endometrial cancer
      risk for 32 genes implicated in hereditary endometrial cancer, and presents a
      summary of rare germline variants in these 32 genes detected by analysis of quasi
      population-based endometrial cancer patients from The Cancer Genome Atlas
      project. This comprehensive investigation has led to the conclusion that
      convincing evidence currently exists to support clinical testing of only six of
      these genes for diagnosis of hereditary endometrial cancer. Testing of
      endometrial cancer patients for the remaining genes should be considered in the
      context of research studies, as a means to better establish the level of
      endometrial cancer risk, if any, associated with genetic variants that are
      deleterious to gene or protein function. It is acknowledged that clinical testing
      of endometrial cancer patients for several genes included on commercial panels
      may provide actionable findings in relation to risk of other cancers, but these
      should be considered secondary or incidental findings and not conclusive evidence
      for diagnosis of inherited endometrial cancer. In summary, this review and
      analysis provides a comprehensive report of current evidence to guide the
      selection of genes for clinical and research gene testing of germline DNA from
      endometrial cancer patients.

PMID- 28452375
TI  - Evaluation of the osseointegration of dental implants coated with calcium
      carbonate: an animal study.
AB  - In an attempt to overcome the limitations of titanium in dental and orthopaedic
      clinical applications, a new method has been developed to prepare calcium
      carbonate coatings on sandblasted and acid-etched (SA) titanium implants. The
      purpose of this study was to investigate the effect of calcium carbonate-SA (CC
      SA) implants on osseointegration in vivo. The surfaces of SA and CC-SA implants
      were characterised for surface morphology and surface chemistry. Subsequently,
      these two kinds of implants were implanted in the femoral condyles of rabbits.
      The implants were retrieved and prepared for histological and histomorphometric
      evaluation 1, 2, 4, 8 and 12 weeks after implantation. Significantly higher
      values of bone-to-implant contact of the entire implant except the gap area
      (BIC_ALL) and the bone-to-implant contact of the gap area (BIC_GAP) were found in
      animals with the CC-SA implants than in those with the SA implants at 4 weeks.
      Higher values of total gap bone were found in those with the CC-SA implants than
      in those with the SA implants at 1, 2 and 4 weeks. In conclusion, the current
      findings demonstrate that the calcium carbonate coating can improve and
      accelerate the early ingrowth of bone and osseointegration at the early healing
      phase. This may reduce clinical healing times and thus improve implant success
      rates.

PMID- 28452376
TI  - A new approach to transfect NF-kappaB decoy oligodeoxynucleotides into the
      periodontal tissue using the ultrasound-microbubble method.
AB  - The objective of this study is to investigate the effect of the ultrasound
      microbubble technique in nuclear factor kappa B (NF-kappaB) decoy
      oligodeoxynucleotide (ODN) transfection in the gingival tissue in mice. The 6-FAM
      labeled scrambled decoy ODN with microbubbles was applied to the periodontal
      tissue in 8-week-old male C57BL/6J mice by ultrasound radiation at low (LUM-Sc)
      and high (HUM-Sc) intensities to optimize the transfection condition of the
      ultrasound-microbubble method. Histological inspections were performed two hours
      after transfection to compare the expression with that in the sham-operated group
      without ultrasound radiation (A-Sc). Then, an NF-kappaB decoy was transfected
      into the periodontal tissue using the high-intensity ultrasound-microbubble (HUM
      NF) technique to examine the anti-inflammatory effects of the decoy ODN. Western
      blot analysis was performed to investigate the expression of interleukin(IL)
      1beta, IL-6 and intercellular adhesion molecule-1 (ICAM-1) in the gingival
      tissues in the HUM-Sc, the HUM-NF and control groups. The fluorescence microscopy
      results showed that the fluorescent intensity in the periodontal tissues in the
      LUM-Sc and HUM-Sc groups was significantly higher than that in the A-Sc and the
      control groups. The fluorescent intensity in the HUM-Sc group, especially in the
      gingival connective tissue, was the highest of all groups. Western blot analysis
      indicated that the protein expression levels of IL-1beta, IL-6 and ICAM-1 in the
      HUM-NF group were significantly lower than those in the HUM-Sc and the control
      groups. These findings suggest that the high-intensity ultrasound-microbubble
      technique is an effective tool for decoy transfection into the periodontal
      tissue.

PMID- 28452377
TI  - Biofilm three-dimensional architecture influences in situ pH distribution pattern
      on the human enamel surface.
AB  - To investigate how the biofilm three-dimensional (3D) architecture influences in
      situ pH distribution patterns on the enamel surface. Biofilms were formed on
      human tooth enamel in the presence of 1% sucrose or 0.5% glucose plus 0.5%
      fructose. At specific time points, biofilms were exposed to a neutral pH buffer
      to mimic the buffering of saliva and subsequently pulsed with 1% glucose to
      induce re-acidification. Simultaneous 3D pH mapping and architecture of intact
      biofilms was performed using two-photon confocal microscopy. The enamel surface
      and mineral content characteristics were examined successively via optical
      profilometry and microradiography analyses. Sucrose-mediated biofilm formation
      created spatial heterogeneities manifested by complex networks of bacterial
      clusters (microcolonies). Acidic regions (pH<5.5) were found only in the interior
      of microcolonies, which impedes rapid neutralization (taking more than 120 min
      for neutralization). Glucose exposure rapidly re-created the acidic niches,
      indicating formation of diffusion barriers associated with microcolonies
      structure. Enamel demineralization (white spots), rougher surface, deeper lesion
      and more mineral loss appeared to be associated with the localization of these
      bacterial clusters at the biofilm-enamel interface. Similar 3D architecture was
      observed in plaque-biofilms formed in vivo in the presence of sucrose. The
      formation of complex 3D architectures creates spatially heterogeneous acidic
      microenvironments in close proximity of enamel surface, which might correlate
      with the localized pattern of the onset of carious lesions (white spot like) on
      teeth.

PMID- 28452372
TI  - 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.
AB  - HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at
      which common variants with minor allele frequency >5% are associated with kidney
      function. GWAS using more complete reference sets for imputation, such as those
      from The 1000 Genomes project, promise to identify novel loci that have been
      missed by previous efforts. To investigate the value of such a more complete
      variant catalog, we conducted a GWAS meta-analysis of kidney function based on
      the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry
      participants using 1000 Genomes imputed data. We identified 10 novel loci with p
      value < 5 * 10-8 previously missed by HapMap-based GWAS. Six of these loci
      (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique
      to the 1000 Genomes reference panel. Using pathway analysis, we identified 39
      significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene
      sets, which were missed by our previous analyses. Among those, the 10 identified
      novel genes are part of pathways of kidney development, carbohydrate metabolism,
      cardiac septum development and glucose metabolism. These results highlight the
      utility of re-imputing from denser reference panels, until whole-genome
      sequencing becomes feasible in large samples.

PMID- 28452378
TI  - Scharioth Macula Lens: A new intraocular implant for low-vision patients with
      stabilized maculopathy- first experience.
AB  - AIMS: To present the initial results of Scharioth Macula Lens (SML) implantation.
      The SML is a new add-on intraocular lens designed to increase uncorrected near
      visual acuity (UCVA) in patients with stabilized maculopathy. METHODS: Eight
      patients were included in the study. All met the indication criteria before SML
      implantation. An SML was implanted in the better seeing eye. Near and distance
      visual acuity were tested. Possible complications and patient complaints were
      recorded and patients were asked about their quality of vision after SML
      implantation. The examination was carried out on day 1, 1 week, 1, 3 and 6 months
      after surgery. RESULTS: Six-month-results are presented. Apart from one, all
      patients with the SML had good near visual acuity at a recommended reading
      distance of 15 cm. Preoperatively, the mean (min-max) near UCVA was J13 (J8-J16),
      mean distance BCVA was 0.27. Postoperatively, the best results were after 1 month
      - near UCVA was J2.5 (J1-J7), distance BCVA was 0.26. Three months after surgery,
      this decreased to J4.5 (J1-J8); distance VA remained 0.25. Six months
      postoperatively - near vision was J4 (J1-J8) and distance VA was unchanged.
      Patients reported problems with reading speed and reading distance. Daily
      exercise improved their reading ability. One patient converted to wet AMD 3
      months post-implantation. CONCLUSION: The SML is a new hope for low-vision
      patients. It acts as a magnifier in the eye. It is a suitable method for
      increasing near visual acuity in patients with inactive maculopathy.

PMID- 28452379
TI  - Avidity of antineurocytoskeletal antibodies in Alzheimer's disease patients.
AB  - AIMS: To optimise the ELISA method for the avidity of IgG antibodies against
      neurofilament heavy chain (NfH) and to determine the levels and avidity of anti
      NfH antibodies in patients with Alzheimer's disease (AD) and a healthy control
      group. METHODS: Various dilutions of sera and concentrations of urea and sodium
      chloride as chaotropic reagents were tested in the process of the ELISA
      optimisation. The levels and avidity of anti-NfH antibodies were determined in 30
      patients with Alzheimer's disease and 30 age-matched cognitively normal elderly
      adults. RESULTS: Sera dilution 1:200 and urea as a chaotrope in a concentration 6
      mol/L were chosen to be the most suitable for the avidity assay of anti-NfH
      antibodies by ELISA. The results showed no differences in either level or avidity
      of IgG anti-NfH antibodies between AD patients and cognitively normal persons.
      The levels of anti-NfH IgG antibodies inversely correlated with their avidities.
      CONCLUSIONS: We optimised the ELISA method for the determination of anti-NfH
      antibody avidity determination which is suitable for research of anti-NfH
      antibody avidity in patients with neurological diseases associated with
      neurocytoskeletal defects. The determination of serum anti-NfH antibody avidity
      in AD patients seems to have limited diagnostic significance.

PMID- 28452380
TI  - Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast
      activation protein in human glioblastomas.
AB  - BACKGROUND AND AIMS: Proteolytic enzymes contribute to the progression of various
      cancers. We previously reported increased expression of the proline specific
      peptidases dipeptidyl peptidase-IV (DPP-IV) and its closest paralogue fibroblast
      activation protein (FAP) in human glioblastomas. Here we analyze the molecular
      heterogeneity of DPP-IV and FAP in glioblastomas. METHODS: ELISA, isoelectric
      focusing, 1D and 2D electrophoresis followed by WB or enzyme overlay assay were
      utilized to analyze DPP-IV and FAP isoforms. Cell fractionation using a Percoll
      gradient and deglycosylation with PNGase F were performed to analyze the possible
      basis of DPP-IV and FAP microheterogeneity. RESULTS: Molecular forms of DPP-IV
      with an estimated molecular weight of 140-160 kDa and a pI predominantly 5.8 were
      detected in human glioblastoma; in some tumors additional isoforms with a more
      acidic (3.5-5.5) as well as alkaline (8.1) pI were revealed. Using 2D
      electrophoresis, two to three molecular forms of FAP with an alkaline (7.0-8.5)
      pI and an estimated MW of 120-140 kDa were identified in glioblastoma tissues. In
      glioma cell lines in vitro, several isoforms of both enzymes were expressed,
      however the alkalic forms present in glioblastoma tissues were not detected.
      Removal of N-linked oligosaccharides decreased the estimated molecular weight of
      both enzymes; the overall pattern of molecular forms nevertheless remained
      unchanged. CONCLUSION: Several isoforms of DPP-IV and FAP are present in
      glioblastoma tissue. The absence of alkaline isoforms of both enzymes in glioma
      cell lines however suggests that isoforms from other, most likely stromal, cell
      types contribute to the overall pattern seen in glioblastoma tissues.

PMID- 28452381
TI  - Transcriptome analysis reveals distinct gene expression profiles in astrocytoma
      grades II-IV.
AB  - BACKGROUND: Astrocytoma is the most prevalent form of primary brain cancer
      categorized into four histological grades by the World Health Organization.
      Investigation into individual grades of astrocytoma by previous studies has
      provided some insight into dysregulation of regulatory networks associated with
      increasing astrocytoma grades. However, further understanding of key mechanisms
      that distinguish different astrocytoma grades is required to facilitate targeted
      therapies. METHODS: In this study, we utilized a large cohort of publicly
      available RNA sequencing data from patients with diffuse astrocytoma (grade II),
      anaplastic astrocytoma (grade III), primary glioblastoma (grade IV), secondary
      glioblastoma (grade IV), recurrent glioblastoma (grade IV), and normal brain
      samples to identify genetic similarities and differences between these grades
      using bioinformatics applications. RESULTS: Our analysis revealed a distinct gene
      expression pattern between grade II astrocytoma and grade IV glioblastoma (GBM).
      We also identified genes that were exclusively expressed in each of the
      astrocytoma grades. Furthermore, we identified known and novel genes involved in
      key pathways in our study. Gene set enrichment analysis revealed a distinct
      expression pattern of transcriptional regulators in primary GBM. Further
      investigation into molecular processes showed that the genes involved in cell
      proliferation and invasion were shared across all subtypes of astrocytoma. Also,
      the number of genes involved in metastasis, regulation of cell proliferation, and
      apoptosis increased with tumor grade. CONCLUSIONS: We confirmed existing findings
      and shed light on some important genes and molecular processes that will improve
      our understanding of glioma biology.

PMID- 28452382
TI  - Electro-responsive polyelectrolyte-coated surfaces.
AB  - The anchoring of polymer chains at solid surfaces is an efficient way to modify
      interfacial properties like the stability and rheology of colloidal dispersions,
      lubrication and biocompatibility. Polyelectrolytes are good candidates for the
      building of smart materials, as the polyion chain conformation can often be tuned
      by manipulation of different physico-chemical variables. However, achieving
      efficient and reversible control of this process represents an important
      technological challenge. In this regard, the application of an external
      electrical stimulus on polyelectrolytes seems to be a convenient control
      strategy, for several reasons. First, it is relatively easy to apply an electric
      field to the material with adequate spatiotemporal control. In addition, in
      contrast to chemically induced changes, the molecular response to a changing
      electric field occurs relatively quickly. If the system is properly designed,
      this response can then be used to control the magnitude of surface properties. In
      this work we discuss the effect of an external electric field on the adhesion and
      lubrication properties of several polyelectrolyte-coated surfaces. The influence
      of the applied field is investigated at different pH and salt conditions, as the
      polyelectrolyte conformation is sensitive to these variables. We show that it is
      possible to fine tune friction and adhesion using relatively low applied fields.

PMID- 28452383
TI  - The effect of pressure on the crystallization of rapidly supercooled zirconium
      melts.
AB  - Molecular dynamics simulations have been performed to explore the effect of
      pressure (P) on the crystallization of zirconium (Zr) under rapid cooling. The
      structural evolutions have been analysed in terms of the system energy, the pair
      distribution function and the largest standard cluster analysis. It was found
      that at the cooling rate of 1.0 * 1011 K s-1, which can crystallize Zr melts into
      hcp crystals via the bcc intermediate state under zero pressure, the critical
      pressure (Pc) for vitrification is about 28.75 GPa, and the larger the pressure,
      the higher the glass transition temperature Tg. At P < Pc the Ostwald's step rule
      is applied to Zr melts. Crystallization of rapidly super-cooled Zr melts under
      pressure always begins with the bcc phase and ends in the hcp crystal; the higher
      the pressure, the lower the onset temperature (Tc) of crystallization. Unlike the
      single-intermediate-state crystallization (SisC) under zero pressure, multiple
      intermediate-state crystallization (MisC) is usually observed under pressure.
      Structural analysis reveals that if nucleation is essentially completed at the
      end of the first crystalline (bcc-dominated) stage, MisC will occur; otherwise,
      SisC occurs. The origin of such an observation is also discussed from the effect
      of pressure upon the thermodynamics and kinetics factors. These findings are
      useful for comprehensively understanding the solidification of metals under
      pressure.

PMID- 28452384
TI  - An academic researcher's guide to increased impact on regulatory assessment of
      chemicals.
AB  - The interactions between academic research and regulatory assessment of chemicals
      may in theory seem straightforward: researchers perform studies, and these
      studies are used by regulators for decision-making. However, in practice the
      situation is more complex, and many factors decide a research study's regulatory
      use. According to several EU chemical legislations, all available and relevant
      studies can be used in hazard and risk assessment of chemicals. However, in
      practice, standard tests conducted under GLP and sponsored and provided by
      industry are predominantly used. Peer-reviewed studies from independent sources
      are often disregarded or disputed since they often do not comply with regulatory
      data requirements and quality criteria. To help bridge such a gap, the aim of
      this paper is to give an overview of the general workings of legislation of
      chemicals and propose a set of actions to increase the usability of research
      data. In the end, this may increase the use of academic research for decision
      making and ultimately result in more science-based policies. From a policy
      perspective, useful scientific evidence comprises those studies that are
      sufficiently reliable and relevant. This is not in contradiction to the aims of
      research and generally accepted scientific standards.

PMID- 28452385
TI  - Nanoengineering of aggregation-free and thermally-stable gold nanoparticles in
      mesoporous frameworks.
AB  - Loading catalytically active, aggregation-free and thermally stable metal
      nanoparticles (NPs) on a high surface area support represents a major interest in
      heterogeneous catalysis. Current synthetic approaches to these hybrid catalysts,
      however, still lack controllability in the thermal stability of metal NPs,
      particularly at high temperatures in the absence of organic ligands. We herein
      report a facile "co-assembly" methodology to prepare aggregation-free, ligand
      free and thermally stable mesoporous hybrid nanocatalysts of metal-oxides and
      metal-carbons. Immobilization of catalytically active gold NPs (AuNPs) within
      high surface area mesoporous frameworks was achieved via the polymer-directed co
      assembly of chemically and structurally equivalent Pluronic P-123 and
      poly(ethylene oxide)-modified metallic gold NPs (AuNP-PEO) as co-structure
      directing-agents. The in situ immobilization of AuNPs partially embedded into
      periodically ordered mesoporous frameworks imposed a three-dimensional
      "nanoconfinement" effect and essentially enhanced the long-term thermal stability
      of AuNPs up to 800  degrees C. The mesoporous hybrids retained a high surface
      accessibility of AuNPs and they had a fantastic high-temperature catalytic
      durability (>130 h at 375  degrees C) confirmed by two model catalytic reactions,
      including aerobic oxidation of benzyl alcohol and CO oxidation, respectively. Our
      results may offer a new realm of possibilities for the rational applications of
      thermally stable nanocatalysts in renewable energy technology and high
      temperature catalysis.

PMID- 28452386
TI  - sigma-Hammett parameter: a strategy to enhance both photo- and electro
      luminescence features of heteroleptic copper(i) complexes.
AB  - This work studies the effect of the sigma-Hammett parameter (sigmap) - i.e., the
      sigma-donation effect caused by substitution at the para position of a bipyridine
      ligand (4,4'-R2bipy, where R is MeO, Me, H, NO2) - on both the photo- and electro
      luminescence features of a series of heteroleptic copper(i) complexes - i.e.,
      [Cu(N^N)(P^P)]+ where N^N and P^P ligands are R2bipy and Xantphos, respectively.
      By virtue of a comprehensive photophysical, theoretical, and thin-film lighting
      device - i.e., light-emitting electrochemical cells (LECs) - investigation, we
      note a clear relationship between the sigmap and the photo- and electro
      luminescence parameters, such as photoluminescence quantum yields, excited-state
      lifetimes, and emission maxima, as well as device brightness, stability, and
      efficacy, respectively. As the most relevant finding, the substitution with the
      group featuring the most negative sigmap - i.e., MeO - provides a ca. five-fold
      enhancement of all of the aforementioned figures-of-merit upon comparison within
      the series of complexes. As such, this work provides a new guideline for a device
      optimization through a rational ligand design for heteroleptic copper(i)
      complexes.

PMID- 28452387
TI  - Correction: Atomic layer deposition of Cu(i) oxide films using Cu(ii)
      bis(dimethylamino-2-propoxide) and water.
AB  - Correction for 'Atomic layer deposition of Cu(i) oxide films using Cu(ii)
      bis(dimethylamino-2-propoxide) and water' by J. R. Avila, et al., Dalton Trans.,
      2017, DOI: .

PMID- 28452388
TI  - An updated roadmap for the integration of metal-organic frameworks with
      electronic devices and chemical sensors.
AB  - Metal-organic frameworks (MOFs) are typically highlighted for their potential
      application in gas storage, separations and catalysis. In contrast, the unique
      prospects these porous and crystalline materials offer for application in
      electronic devices, although actively developed, are often underexposed. This
      review highlights the research aimed at the implementation of MOFs as an integral
      part of solid-state microelectronics. Manufacturing these devices will critically
      depend on the compatibility of MOFs with existing fabrication protocols and
      predominant standards. Therefore, it is important to focus in parallel on a
      fundamental understanding of the distinguishing properties of MOFs and
      eliminating fabrication-related obstacles for integration. The latter implies a
      shift from the microcrystalline powder synthesis in chemistry labs, towards film
      deposition and processing in a cleanroom environment. Both the fundamental and
      applied aspects of this two-pronged approach are discussed. Critical directions
      for future research are proposed in an updated high-level roadmap to stimulate
      the next steps towards MOF-based microelectronics within the community.

PMID- 28452389
TI  - Chiral metallosupramolecular architectures.
AB  - Over the past few decades, supramolecular chirality in discrete
      metallosupramolecular architectures has received considerable attention. In this
      review, a comprehensive summary of discrete, chiral coordination-driven
      structures, including helices, metallacycles, metallocages, etc., is presented.
      Although chirality can be introduced prior to, during or even after the
      coordination self-assembly process, this review puts major emphasis on the more
      recent development of metallosupramolecular architectures from chiral components,
      where chirality arises from the enantiopure or racemic scaffolds (bridging or
      auxiliary ligand). Special attention will be paid to homochiral metallo
      assemblies using achiral components where chirality is obtained as a consequence
      of the twisting of the ligands. Additionally, the potential applications of
      homochiral metallosupramolecular architectures are also discussed. We hope that
      this review will be of interest to researchers attempting to design new elaborate
      homochiral metallosupramolecular architectures with even greater complexity and
      potential for functions such as chiral recognition, enantiomer separation,
      asymmetric catalysis, nonlinear sensors, and devices.

PMID- 28452390
TI  - Benzodiazines: recent synthetic advances.
AB  - Benzodiazines (diazonaphthalenes with both nitrogens in the same ring) -
      cinnolines (1,2-benzodiazine), quinazolines (1,3-benzodiazine), phthalazines (2,3
      benzodiazine) and quinoxalines (1,4-benzodiazine) - are important class of
      compounds with broad biological properties and wide application in pharmaceutical
      as well as agrochemical arenas. These diazaheterocycles are present in a wide
      variety of bioactive natural products as well as synthetic molecules that are
      good drug candidates constituting key structural units responsible for their
      pronounced therapeutic activities. Their rapidly growing uses and applications in
      medicinal and agrochemical arenas prompt the researchers for further studies on
      this important group of compounds. In this review, we hope to provide a brief
      overview of the important general methodologies and recent developments towards
      their synthesis and open the door for further progress in this area.

PMID- 28452391
TI  - Yucel Kanpolat, MD (1941-2016).

PMID- 28452392
TI  - Correction: Alagoz F, Yildirim AE, Sahinoglu M, Korkmaz M, Secer M, Celik H, Yel
      C, Guvenc Y, Uckun OM, Narin F, Daglioglu E, Belen AD. Traumatic Acute Subdural
      Hematomas: Analysis of Outcomes and Predictive Factors at a Single Center. Turk
      Neurosurg 2017; 27(2):187-191.

PMID- 28452393
TI  - Caregiver Talk and Medical Risk as Predictors of Language Outcomes in Full Term
      and Preterm Toddlers.
AB  - This study examined associations between caregiver talk and language skills in
      full term (FT) and preterm (PT) children (n = 97). All-day recordings of
      caregiver-child interactions revealed striking similarities in amount of
      caregiver talk heard by FT and PT children. Children who heard more caregiver
      talk at 16 months demonstrated better knowledge- and processing-based language
      skills at 18 months. The unique contributions of caregiver talk were tempered by
      medical risk in PT children, especially for processing speed. However, there was
      no evidence that birth status or medical risk moderated the effects of caregiver
      talk. These findings highlight the role of caregiver talk in shaping language
      outcomes in FT and PT children and offer insights into links between
      neurodevelopmental risk and caregiver-child engagement.

PMID- 28452394
TI  - Hierarchical organization and genetically separable subfamilies of PSD95
      postsynaptic supercomplexes.
AB  - PSD95 is an abundant postsynaptic scaffold protein in glutamatergic synapses that
      assembles into supercomplexes composed of over 80 proteins including
      neurotransmitter receptors, ion channels and adhesion proteins. How these diverse
      constituents are organized into PSD95 supercomplexes in vivo is poorly
      understood. Here, we dissected the supercomplexes in mice combining endogenous
      gene-tagging, targeted mutations and quantitative biochemical assays. Generating
      compound heterozygous mice with two different gene-tags, one on each Psd95
      allele, showed that each ~1.5 MDa PSD95-containing supercomplex contains on
      average two PSD95 molecules. Gene-tagging the endogenous GluN1 and PSD95 with
      identical Flag tags revealed N-methyl D-aspartic acid receptors (NMDARs)
      containing supercomplexes that represent only 3% of the total population of PSD95
      supercomplexes, suggesting there are many other subtypes. To determine whether
      this extended population of different PSD95 supercomplexes use genetically
      defined mechanisms to specify their assembly, we tested the effect of five
      targeted mouse mutations on the assembly of known PSD95 interactors, Kir2.3, Arc,
      IQsec2/BRAG1 and Adam22. Unexpectedly, some mutations were highly selective,
      whereas others caused widespread disruption, indicating that PSD95 interacting
      proteins are organized hierarchically into distinct subfamilies of ~1.5 MDa
      supercomplexes, including a subpopulation of Kir2.3-NMDAR ion channel-channel
      supercomplexes. Kir2.3-NMDAR ion channel-channel supercomplexes were found to be
      anatomically restricted to particular brain regions. These data provide new
      insight into the mechanisms that govern the constituents of postsynaptic
      supercomplexes and the diversity of synapse types. Read the Editorial Highlight
      for this article on page 500. Cover Image for this issue: doi. 10.1111/jnc.13811.

PMID- 28452395
TI  - Temporary impact of blood donation on physical performance and hematologic
      variables in women.
AB  - BACKGROUND: No former studies have examined how blood donation influences
      physical performance in women, who due to menstruation may have a slower recovery
      of performance. Therefore, the aim of this study was to clarify how VO2peak ,
      time trial (TT) performance, and hematologic variables are affected in 18 iron
      sufficient (plasma ferritin [P-ferritin] > 30 ug/L) women after a standard 450-mL
      blood donation. STUDY DESIGN AND METHODS: VO2peak , TT performance, and blood
      variables were measured at baseline and 3, 7, 14, 21, and 28 days after blood
      donation in 18 iron-sufficient women. Anthropometrics were measured at baseline
      and Day 28. RESULTS: VO2peak was reduced by 7.5 +/- 1.1% from 2973 +/- 87 mL/min
      at baseline to 2765 +/- 73 mL/min 3 days after blood donation and remained below
      baseline until 28 days. The TT performance was reduced by 5.2 +/- 1.0% from
      baseline (868 +/- 31 sec) to Day 3 (915 +/- 29 sec), but was not different from
      baseline 14 days after blood donation. Blood hemoglobin (B-Hb) concentration
      declined by 7.6 +/- 2.1% from 8.4 +/- 0.1 to 7.8 +/- 0.1 mmol/L at baseline and
      on Day 3, respectively. P-ferritin at baseline was 58 +/- 7 ug/L and it decreased
      (55 +/- 3%) to a nadir of 24 +/- 3 ug/L 28 days after blood donation and remained
      lower at 36 +/- 4 ug/L after 90 days. CONCLUSION: VO2peak and B-Hb were only
      recovered 28 days after a blood donation whereas TT performance was back to
      baseline 14 days after blood donation.

PMID- 28452396
TI  - Reversible Supracolloidal Self-Assembly of Cobalt Nanoparticles to Hollow Capsids
      and Their Superstructures.
AB  - The synthesis and spontaneous, reversible supracolloidal hydrogen bond-driven
      self-assembly of cobalt nanoparticles (CoNPs) into hollow shell-like capsids and
      their directed assembly to higher order superstructures is presented. CoNPs and
      capsids form in one step upon mixing dicobalt octacarbonyl (Co2 CO8 ) and p
      aminobenzoic acid (pABA) in 1,2-dichlorobenzene using heating-up synthesis
      without additional catalysts or stabilizers. This leads to pABA capped CoNPs
      (core ca. 5 nm) with a narrow size distribution. They spontaneously assemble into
      tunable spherical capsids (d~50-200 nm) with a few-layered shells, as driven by
      inter-nanoparticle hydrogen bonds thus warranting supracolloidal self-assembly.
      The capsids can be reversibly disassembled and reassembled by controlling the
      hydrogen bonds upon heating or solvent exchanges. The superparamagnetic nature of
      CoNPs allows magnetic-field-directed self-assembly of capsids to capsid chains
      due to an interplay of induced dipoles and inter-capsid hydrogen bonds. Finally,
      self-assembly on air-water interface furnishes lightweight colloidal framework
      films.

PMID- 28452397
TI  - PdPt Alloy Nanocatalysts Supported on TiO2 : Maneuvering Metal-Hydrogen
      Interactions for Light-Driven and Water-Donating Selective Alkyne
      Semihydrogenation.
AB  - Low power consumption and minimal potential hazards are ultimate goals for the
      modern development of chemical manufacturing; however, it often reduces the
      selectivity of chemical reactions by implementing a new reaction system. A
      nanocatalyst design is reported for achieving efficient and selective alkyne
      semihydrogenation through the photocatalytic hydrogen transfer from water, which
      avoids the use of a heat source and explosive H2 . The PdPt catalytic sites that
      are implemented on the TiO2 photocatalyst hold the key to achieving both high
      activity and selectivity. As compared with pure Pd or Pt, the alloy cocatalysts
      can better harness H diffusion/desorption for selective semihydrogenation as well
      as suppress competitive H2 evolution. This work opens up new possibilities for
      green and selective alkyne semihydrogenation and highlights the importance of
      lattice engineering to catalytic selectivity.

PMID- 28452398
TI  - ACBC to Balcite: Bioinspired Synthesis of a Highly Substituted High-Temperature
      Phase from an Amorphous Precursor.
AB  - Energy-efficient synthesis of materials locked in compositional and structural
      states far from equilibrium remains a challenging goal, yet biomineralizing
      organisms routinely assemble such materials with sophisticated designs and
      advanced functional properties, often using amorphous precursors. However,
      incorporation of organics limits the useful temperature range of these materials.
      Herein, the bioinspired synthesis of a highly supersaturated calcite (Ca0.5 Ba0.5
      CO3 ) called balcite is reported, at mild conditions and using an amorphous
      calcium-barium carbonate (ACBC) (Ca1-x Ba x CO3 .1.2H2 O) precursor. Balcite not
      only contains 50 times more barium than the solubility limit in calcite but also
      displays the rotational disorder on carbonate sites that is typical for high
      temperature calcite. It is significantly harder (30%) and less stiff than
      calcite, and retains these properties after heating to elevated temperatures.
      Analysis of balcite local order suggests that it may require the formation of the
      ACBC precursor and could therefore be an example of nonclassical nucleation.
      These findings demonstrate that amorphous precursor pathways are powerfully
      enabling and provide unprecedented access to materials far from equilibrium,
      including high-temperature modifications by room-temperature synthesis.

PMID- 28452399
TI  - Does the ability to express different emotions predict different indices of
      physical health? A skill-based study of physical symptoms and heart rate
      variability.
AB  - OBJECTIVES: The outward expression of emotion has been frequently associated with
      better health outcomes, whereas suppressing emotion is thought to contribute to
      worse physical health. However, work has typically focused on trait expressive
      tendencies and the possibility that individual differences in the ability to
      express specific emotions may also be associated with health has not been widely
      tested. DESIGN: A cross-sectional study of community dwelling adults. METHODS:
      One hundred and twenty-eight participants aged 18-88 years completed
      questionnaires assessing demographics and health status, before attending a
      testing session in which resting heart rate variability (HRV) was assessed.
      Participants then completed a performance-based test of expressive regulatory
      skill in which they were instructed to enhance and suppress their emotional
      expressions while they watched film clips validated to elicit amusement, sadness,
      and anger. Participants rated subjective emotional experience before and after
      each clip, and their degree of expressivity was scored using FACS-based Noldus
      FaceReader. RESULTS: Missing data resulted in a final sample size of 117. Linear
      regressions controlling for age, sex, diagnoses, and trait emotion revealed that
      greater ability to enhance sad expressions was associated with higher HRV while
      the ability to enhance expressions of joy was associated with lower symptom
      interference. In parallel models, the ability to flexibly regulate (both enhance
      and suppress) expressions of joy and sadness was also associated with lower
      symptom interference. CONCLUSIONS: Findings suggest that the ability to regulate
      expressions of both sadness and joy is associated with health indices even when
      controlling for trait affect and potential confounds. The present findings offer
      early evidence that individual differences in the ability to regulate the outward
      expression of emotion may be relevant to health and suggest that expressive
      regulatory skills offer a novel avenue for research and intervention. Statement
      of contribution What is already known on this subject The tendency to outwardly
      express felt emotion generally predicts better health, whereas expressive
      suppression typically predicts worse health outcomes. Most work has been based on
      trait assessments; however, the ability to regulate the expression of felt
      emotion can be objectively assessed using performance-based tests. Prior work in
      mental health suggests that the ability to flexibly up- and downregulate the
      expression of emotion predicts better outcomes. What does this study add The
      first evidence that the ability to flexibly regulate expressions predicts indices
      of health. Skill in both expressing and suppressing facial expressions predicts
      better reported health. Skills with different emotions differentially predict
      symptom interference and cardiac vagal tone.

PMID- 28452400
TI  - Catalytic Desymmetrization by C-H Functionalization as a Solution to the Chiral
      Methyl Problem.
AB  - Breaking the mirror (plane): A palladium-catalyzed desymmetrization strategy via
      beta C-H activation provides an alternate approach for solving the age-old
      challenge of introducing an alpha-methyl stereocenter to a molecule.

PMID- 28452402
TI  - High-Performance Piezoelectric Nanogenerators with Imprinted P(VDF-TrFE)/BaTiO3
      Nanocomposite Micropillars for Self-Powered Flexible Sensors.
AB  - Piezoelectric nanogenerators with large output, high sensitivity, and good
      flexibility have attracted extensive interest in wearable electronics and
      personal healthcare. In this paper, the authors propose a high-performance
      flexible piezoelectric nanogenerator based on piezoelectrically enhanced
      nanocomposite micropillar array of polyvinylidene fluoride-trifluoroethylene
      (P(VDF-TrFE))/barium titanate (BaTiO3 ) for energy harvesting and highly
      sensitive self-powered sensing. By a reliable and scalable nanoimprinting
      process, the piezoelectrically enhanced vertically aligned P(VDF-TrFE)/BaTiO3
      nanocomposite micropillar arrays are fabricated. The piezoelectric device
      exhibits enhanced voltage of 13.2 V and a current density of 0.33 uA cm-2 , which
      an enhancement by a factor of 7.3 relatives to the pristine P(VDF-TrFE) bulk
      film. The mechanisms of high performance are mainly attributed to the enhanced
      piezoelectricity of the P(VDF-TrFE)/BaTiO3 nanocomposite materials and the
      improved mechanical flexibility of the micropillar array. Under mechanical
      impact, stable electricity is stably generated from the nanogenerator and used to
      drive various electronic devices to work continuously, implying its significance
      in the field of consumer electronic devices. Furthermore, it can be applied as
      self-powered flexible sensor work in a noncontact mode for detecting air pressure
      and wearable sensors for detecting some human vital signs including different
      modes of breath and heartbeat pulse, which shows its potential applications in
      flexible electronics and medical sciences.

PMID- 28452403
TI  - Highly Conductive Water-Based Polymer/Graphene Nanocomposites for Printed
      Electronics.
AB  - The preparation and characterization of highly conductive carbon inks is
      described based on nanocomposites that combine a polystyrene-acrylic resin or
      water-soluble polymers with a hydrophilic graphene/carbon nanotube hybrid. The
      water-based carbon inks showed high electrical conductivity and could be
      effectively used in advanced technologies such as gravure printing for printed
      electronics. Moreover, the conductivity was shown to be increased with a power
      law of the nanohybrid volume fraction, with an exponent close to that predicted
      from the percolation theory, indicating a limited impact of the polymer tunneling
      barrier on the electrical conductivity of such nanocomposites.

PMID- 28452401
TI  - Pericardial fat volume and incident atrial fibrillation in the Multi-Ethnic Study
      of Atherosclerosis and Jackson Heart Study.
AB  - OBJECTIVE: To determine whether greater pericardial fat volume would be
      associated with increased risk of incident atrial fibrillation (AF). METHODS: In
      the Multi-Ethnic Study of Atherosclerosis and Jackson Heart Study, pericardial
      fat volume was quantified by computed tomography. Incident AF was identified from
      discharge diagnosis codes, study electrocardiograms, and Medicare claims.
      RESULTS: Among 7,991 participants, 40% were African American, 32% white, 18%
      Hispanic, and 10% Chinese American; mean age was 62 years; 55% were women. During
      an average of 10.0 years of follow-up in the Multi-Ethnic Study of
      Atherosclerosis and 4.5 years in the Jackson Heart Study, 756 incident AF cases
      were identified. After adjustment for age, sex, study, race/ethnicity, height,
      glucose status, systolic blood pressure, treated hypertension, and BMI, greater
      pericardial fat volume was associated with higher AF risk in Hispanics (hazard
      ratio 1.24 per SD, 95% confidence interval 1.05-1.46) but not overall (hazard
      ratio 1.06, 95% confidence interval 0.97-1.15). In mediation analysis,
      pericardial fat volume partially mediated the association of BMI with incident AF
      in Hispanics. CONCLUSIONS: After adjustment for BMI, greater pericardial fat
      volume was associated with incident AF in Hispanics but not overall. Additional
      research is needed on the mechanisms by which pericardial fat volume is related
      to increased AF risk and possible differences by race/ethnicity.

PMID- 28452404
TI  - The effect of a lifestyle intervention on pregnancy and postpartum dietary
      patterns determined by factor analysis.
AB  - OBJECTIVE: Optimizing maternal diet during pregnancy improves maternal and infant
      health. This study assessed the effect of an antenatal lifestyle intervention for
      women with overweight or obesity on dietary patterns during pregnancy and post
      partum. METHODS: This study is a secondary analysis of a randomized controlled
      trial in which pregnant women (BMI >= 25 kg/m2 ) received lifestyle advice (n =
      943) or standard care (n = 924). Dietary pattern analysis was undertaken using
      factor analysis with comparisons between trial entry and 28 weeks, 36 weeks, and
      4 months post partum. RESULTS: The dietary pattern analysis revealed two distinct
      patterns: "prudent" and "Western." There was a significant difference between
      groups in the change over time for both patterns (P < 0.001). For the prudent
      score, the lifestyle group had higher scores at all times after trial entry
      compared with standard care, while for the Western score, the lifestyle group had
      a lower score at 28 weeks. The intervention effect differed based on trial entry
      BMI (P =  0.043) and smoking (P = 0.019), with higher prudent scores for women
      with obesity compared with overweight and smokers compared with nonsmokers.
      CONCLUSIONS: The provision of an antenatal lifestyle intervention for women with
      overweight and obesity was associated with an improvement in dietary patterns
      that persisted post partum. This has important implications for the future
      consideration of optimal dietary intervention components to include in antenatal
      lifestyle interventions.

PMID- 28452405
TI  - Modulations of cognitive flexibility in obsessive compulsive disorder reflect
      dysfunctions of perceptual categorization.
AB  - BACKGROUND: Despite cognitive inflexibility is trait like in obsessive compulsive
      disorder (OCD) patients and underlies clinical symptomatology, it is elusive at
      what stage of information processing deficits, leading to cognitive
      inflexibility, emerges. We hypothesize that inhibitory control mechanisms during
      early stimulus categorization and integration into a knowledge system underlie
      these deficits. METHODS: We examined N = 25 adolescent OCD patients and matched
      healthy controls (HC) in a paradigm manipulating the importance of the knowledge
      system to perform task switching. This was done using a paradigm in which task
      switches were signaled either by visual stimuli or by working memory processes.
      This was combined with event-related potential recordings and source
      localization. RESULTS: Obsessive compulsive disorder patients showed increased
      switch costs in the memory as compared with the cue-based block, while HC showed
      similar switch costs in both blocks. At the neurophysiological level, these
      changes in OCD were not reflected by the N2 and P3 reflecting response-associated
      processes but by the P1 reflecting inhibitory control during sensory
      categorization processes. Activation differences in the right inferior frontal
      gyrus and superior temporal gyrus are associated with the P1 effect. CONCLUSIONS:
      Cognitive flexibility in adolescent OCD patients is strongly modulated by working
      memory load. Contrary to common sense, not response-associated processes, but
      inhibitory control mechanisms during early stimulus categorization processes are
      likely to underlie cognitive inflexibility in OCD. These processes are associated
      with right inferior frontal and superior temporal gyrus mechanisms.

PMID- 28452406
TI  - The Sensitive Period for Tactile Remapping Does Not Include Early Infancy.
AB  - Visual input during development seems crucial in tactile spatial perception,
      given that late, but not congenitally, blind people are impaired when skin-based
      and tactile external representations are in conflict (when crossing the limbs).
      To test whether there is a sensitive period during which visual input is
      necessary, 14 children (age = 7.95) and a teenager (LM; age = 17.38) deprived of
      early vision by cataracts, and whose sight was restored during the first 5 months
      and at age 7, respectively, were tested. Tactile localization with arms crossed
      and uncrossed was measured. Children showed a crossing effect indistinguishable
      from a control group (Ns = 28, age = 8.24), whereas LM showed no crossing effect
      (Ns controls = 14, age = 20.78). This demonstrates a sensitive period which,
      critically, does not include early infancy.

PMID- 28452407
TI  - Individual, social, and family factors associated with high school dropout among
      low-SES youth: Differential effects as a function of immigrant status.
AB  - BACKGROUND: In most Western countries, the individual, social, and family
      characteristics associated with students' dropout in the general population are
      well documented. Yet, there is a lack of large-scale studies to establish whether
      these characteristics have the same influence for students with an immigrant
      background. AIMS: The first aim of this study was to assess the differences
      between first-, second-, and third-generation-plus students in terms of the
      individual, social, and family factors associated with school dropout. Next, we
      examined the differential associations between these individual, social, and
      family factors and high school dropout as a function of students' immigration
      status. SAMPLE: Participants were 2291 students (54.7% with an immigrant
      background) from ten low-SES schools in Montreal (Quebec, Canada). METHOD:
      Individual, social, and family predictors were self-reported by students in
      secondary one (mean age = 12.34 years), while school dropout status was obtained
      five or 6 years after students were expected to graduate. RESULTS: Results of
      logistic regressions with multiple group latent class models showed that first-
      and second-generation students faced more economic adversity than third
      generation-plus students and that they differed from each other and with their
      native peers in terms of individual, social, and family risk factors. Moreover,
      40% of the risk factors considered in this study were differentially associated
      with first-, second-, and third-generation-plus students' failure to graduate
      from high school. CONCLUSION: These results provide insights on immigrant and non
      immigrant inner cities' students experiences related to school dropout. The
      implications of these findings are discussed.

PMID- 28452408
TI  - Psychological interventions for coronary heart disease.
AB  - BACKGROUND: Coronary heart disease (CHD) is the most common cause of death
      globally, although mortality rates are falling. Psychological symptoms are
      prevalent for people with CHD, and many psychological treatments are offered
      following cardiac events or procedures with the aim of improving health and
      outcomes. This is an update of a Cochrane systematic review previously published
      in 2011. OBJECTIVES: To assess the effectiveness of psychological interventions
      (alone or with cardiac rehabilitation) compared with usual care (including
      cardiac rehabilitation where available) for people with CHD on total mortality
      and cardiac mortality; cardiac morbidity; and participant-reported psychological
      outcomes of levels of depression, anxiety, and stress; and to explore potential
      study-level predictors of the effectiveness of psychological interventions in
      this population. SEARCH METHODS: We updated the previous Cochrane Review searches
      by searching the following databases on 27 April 2016: CENTRAL in the Cochrane
      Library, MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO).
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) of
      psychological interventions compared to usual care, administered by trained
      staff, and delivered to adults with a specific diagnosis of CHD. We selected only
      studies estimating the independent effect of the psychological component, and
      with a minimum follow-up of six months. The study population comprised of adults
      after: a myocardial infarction (MI), a revascularisation procedure (coronary
      artery bypass graft (CABG) or percutaneous coronary intervention (PCI)), and
      adults with angina or angiographically defined coronary artery disease (CAD).
      RCTs had to report at least one of the following outcomes: mortality (total- or
      cardiac-related); cardiac morbidity (MI, revascularisation procedures); or
      participant-reported levels of depression, anxiety, or stress. DATA COLLECTION
      AND ANALYSIS: Two review authors independently screened titles and abstracts of
      all references for eligibility. A lead review author extracted study data, which
      a second review author checked. We contacted study authors to obtain missing
      information. MAIN RESULTS: This review included 35 studies which randomised
      10,703 people with CHD (14 trials and 2577 participants added to this update).
      The population included mainly men (median 77.0%) and people post-MI (mean 65.7%)
      or after undergoing a revascularisation procedure (mean 27.4%). The mean age of
      participants within trials ranged from 53 to 67 years. Overall trial reporting
      was poor, with around a half omitting descriptions of randomisation sequence
      generation, allocation concealment procedures, or the blinding of outcome
      assessments. The length of follow-up ranged from six months to 10.7 years (median
      12 months). Most studies (23/35) evaluated multifactorial interventions, which
      included therapies with multiple therapeutic components. Ten studies examined
      psychological interventions targeted at people with a confirmed psychopathology
      at baseline and two trials recruited people with a psychopathology or another
      selecting criterion (or both). Of the remaining 23 trials, nine studies recruited
      unselected participants from cardiac populations reporting some level of
      psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety),
      10 studies did not report these characteristics, and only three studies excluded
      people with psychopathology.Moderate quality evidence showed no risk reduction
      for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to
      1.05; participants = 7776; studies = 23) or revascularisation procedures (RR
      0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care.
      Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI
      0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79,
      95% CI 0.63 to 0.98). There was also low or very low quality evidence that
      psychological interventions improved participant-reported levels of depressive
      symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE
      = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD 
      0.56, 95% CI -0.88 to -0.24; GRADE = very low).There was substantial statistical
      heterogeneity for all psychological outcomes but not clinical outcomes, and there
      was evidence of small-study bias for one clinical outcome (cardiac mortality:
      Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P =
      0.012). Meta-regression exploring a limited number of intervention
      characteristics found no significant predictors of intervention effects for total
      mortality and cardiac mortality. For depression, psychological interventions
      combined with adjunct pharmacology (where deemed appropriate) for an underlying
      psychological disorder appeared to be more effective than interventions that did
      not (beta = -0.51, P = 0.003). For anxiety, interventions recruiting participants
      with an underlying psychological disorder appeared more effective than those
      delivered to unselected populations (beta = -0.28, P = 0.03). AUTHORS'
      CONCLUSIONS: This updated Cochrane Review found that for people with CHD, there
      was no evidence that psychological treatments had an effect on total mortality,
      the risk of revascularisation procedures, or on the rate of non-fatal MI,
      although the rate of cardiac mortality was reduced and psychological symptoms
      (depression, anxiety, or stress) were alleviated; however, the GRADE assessments
      suggest considerable uncertainty surrounding these effects. Considerable
      uncertainty also remains regarding the people who would benefit most from
      treatment (i.e. people with or without psychological disorders at baseline) and
      the specific components of successful interventions. Future large-scale trials
      testing the effectiveness of psychological therapies are required due to the
      uncertainty within the evidence. Future trials would benefit from testing the
      impact of specific (rather than multifactorial) psychological interventions for
      participants with CHD, and testing the targeting of interventions on different
      populations (i.e. people with CHD, with or without psychopathologies).

PMID- 28452410
TI  - Hollow Carbon Nanopolyhedra for Enhanced Electrocatalysis via Confined
      Hierarchical Porosity.
AB  - A novel strategy for the fabrication of hollow Co and N-codoped carbon
      nanopolyhedra (H-CoNC) from metal-organic framework (MOF) using in situ
      evaporation of ZnO nanosphere templates is proposed. The excess Zn supply during
      the pyrolysis process is found beneficial in terms of high nitrogen (~9.75 at%),
      relatively homogenous Co?N bonding, and the electrochemically accessible
      hierarchical porous system. Compared with other reported "solid" CoNC of
      identical surface areas, the newly developed H-CoNC shows enhanced kinetic
      current in 0.1 m KOH electrolyte and elevated oxygen reduction reaction (ORR)
      performance in 6 m KOH. The latter exceeds results obtained with the benchmark 20
      wt% Pt/C, which is related to the strong confinement of O2 molecules in the H
      CoNC hierarchical porous system. Furthermore, the H-CoNC displays great tolerance
      toward the methanol crossover and KSCN poisoning. Finally, the assembled Zn-air
      batteries with H-CoNC yield a record open circuit potential (1.59 V vs Zn,
      stabilized at 1.52 V), high power density (331.0 mW cm-2 ), and promising rate
      performance. This work provides a new guideline for the design of MOF-derived
      carbon materials, as well as novel insights into spatial confinement effect
      toward the ORR activity.

PMID- 28452409
TI  - Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot
      midazolam-controlled randomized clinical trial.
AB  - OBJECTIVES: To evaluate feasibility and effects of a sub-anesthetic infusion dose
      of ketamine versus midazolam on suicidal ideation in bipolar depression.
      Neurocognitive, blood and saliva biomarkers were explored. METHODS: Sixteen
      participants with bipolar depression and a Scale for Suicidal Ideation (SSI)
      score of >=4 were randomized to ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg).
      Current pharmacotherapy was maintained excluding benzodiazepines within 24 hours.
      The primary clinical outcome was SSI score on day 1 post-infusion. RESULTS:
      Results supported feasibility. Mean reduction of SSI after ketamine infusion was
      almost 6 points greater than after midazolam, although this was not statistically
      significant (estimate=5.84, SE=3.01, t=1.94, P=.074, 95% confidence interval
      ([CI)]=-0.65 to 12.31). The number needed to treat for response (SSI <4 and at
      least 50% below baseline) was 2.2, and for remission (SSI=0) was 3.2. The
      strongest neurocognitive correlation was between memory improvement on the
      Selective Reminding Test (SRT) and reduction in SSI score on day 1 after ketamine
      (rho=-.89, P=.007). Pre- to post-infusion decrease in serum brain derived
      neurotrophic factor (BDNF) correlated with reduction in SSI from baseline to day
      1 after ketamine (n=5, rho=0.90, P=.037) but not midazolam (P=.087). CONCLUSIONS:
      The study demonstrated feasibility. Suicidal thoughts were lower after ketamine
      than after midazolam at a trend level of significance, likely due to the small
      pilot sample. Memory improvement and BDNF are promising biomarkers. Replication
      is needed in an adequately powered full-scale trial.

PMID- 28452411
TI  - Effect of Thickness of Zirconia Ceramic on Its Masking Ability: An In Vitro
      Study.
AB  - PURPOSE: Color-masking ability of zirconia ceramics as coping materials has not
      been clearly understood in zirconia-based restorations. This in vitro study aimed
      to evaluate the effect of zirconia ceramic thickness on its masking ability, and
      to define a thickness cutoff for the tested ceramic. MATERIALS AND METHODS:
      Ninety zirconia disc specimens, in nine thickness groups including 0.4, 0.6, 0.8,
      1, 1.2, 1.4, 1.6, 1.8, and 2 mm were fabricated. A white substrate and a black
      substrate were prepared. The disc specimens were placed onto the substrates for
      spectrophotometric measurements. A spectrophotometer measured L* , a* , and b*
      color attributes for the specimens. DeltaE value was calculated to determine the
      color difference of specimens on the white and black substrate. Then the DeltaE
      values were compared with an acceptable clinical threshold (DeltaE = 5.5) and an
      ideal threshold (DeltaE = 2.6). Welch test, Games-Howell Post Hoc, one-sample t
      test, and a regression analysis were performed (p < 0.05). RESULTS: The means of
      DeltaE values for the thickness groups of 0.4, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8,
      and 2 mm were 13.0, 11.9, 9.7, 5.0, 4.2, 3.9, 2.2, 1.9, and 1.5, respectively. A
      significant difference was found in the DeltaE value among the groups (p <
      0.0001). An exponential relation was detected between the thickness and the
      DeltaE by the regression analysis (?E = 25.68e-1.45 (thickness) ). CONCLUSIONS:
      The masking ability increased as the zirconia ceramic thickness increased. The
      tested zirconia ceramic had an acceptable clinical masking ability with a minimum
      thickness of 1 mm, and an ideal masking ability with a minimum thickness of 1.6
      mm.

PMID- 28452412
TI  - Lead-free Perovskite Materials (NH4 )3 Sb2 Ix Br9-x.
AB  - A family of perovskite light absorbers (NH4 )3 Sb2 Ix Br9-x (0<=x<=9) was
      prepared. These materials show good solubility in ethanol, a low-cost, hypotoxic,
      and environmentally friendly solvent. The light absorption of (NH4 )3 Sb2 Ix Br9
      x films can be tuned by adjusting I and Br content. The absorption onset for (NH4
      )3 Sb2 Ix Br9-x films changes from 558 nm to 453 nm as x changes from 9 to 0.
      (NH4 )3 Sb2 I9 single crystals were prepared, exhibiting a hole mobility of 4.8
      cm2  V-1  s-1 and an electron mobility of 12.3 cm2  V-1  s-1 . (NH4 )3 Sb2 I9
      solar cells gave an open-circuit voltage of 1.03 V and a power conversion
      efficiency of 0.51 %.

PMID- 28452413
TI  - Characterizing ontogenetic habitat shifts in marine fishes: advancing nascent
      methods for marine spatial management.
AB  - Niche requirements and habitat resource partitioning by conspecific fishes of
      different sizes are significant knowledge gaps in the species distribution
      modelling domain. Management actions and operations are typically concentrated on
      static habitats, or specific areas of interest, without considering movement
      patterns of species associated with ontogenetic shifts in habitat usage.
      Generalized additive models were used to model the body-length-habitat
      relationships of six fish species. These models were used to identify subsets of
      environmental parameters that drive and explain the continuous length-habitat
      relationships for each of the study species, which vary in their degree of
      ecological and/or commercial importance. Continuous predictive maps of the length
      distributions for each of the six study species across approximately 200 km2 of
      the study area were created from these models. The spatial patterns in habitat
      partitioning by individuals of different body lengths for all six study species
      provide strong evidence for ontogenetic shifts. This highlights the importance of
      considering ontogenetic processes for marine spatial management. Importantly,
      predictive hotspot maps were created that identify potential areas that
      accumulate individuals of similar life stages of multiple species (e.g.,
      multispecies nursery areas). In circumstances where limited resources are
      available for monitoring and management of fish resources, predictive modelling
      is a valuable tool for studying previously overlooked processes such as
      ontogenetic habitat shifts. Predictive modelling provides crucial information
      that elucidates spatial patterns in community composition across mosaics of
      benthic habitats. This novel technique can contribute to the spatial management
      of coastal fish and fisheries by identifying areas that are important for
      different life history stages of multiple fish species.

PMID- 28452414
TI  - Gerd Becker (1940-2017).

PMID- 28452415
TI  - A new parameterization for integrated population models to document amphibian
      reintroductions.
AB  - Managers are increasingly implementing reintroduction programs as part of a
      global effort to alleviate amphibian declines. Given uncertainty in factors
      affecting populations and a need to make recurring decisions to achieve
      objectives, adaptive management is a useful component of these efforts. A major
      impediment to the estimation of demographic rates often used to parameterize and
      refine decision-support models is that life-stage-specific monitoring data are
      frequently sparse for amphibians. We developed a new parameterization for
      integrated population models to match the ecology of amphibians and capitalize on
      relatively inexpensive monitoring data to document amphibian reintroductions. We
      evaluate the capability of this model by fitting it to Oregon spotted frog (Rana
      pretiosa) monitoring data collected from 2007 to 2014 following their
      reintroduction within the Klamath Basin, Oregon, USA. The number of egg masses
      encountered and the estimated adult and metamorph abundances generally increased
      following reintroduction. We found that survival probability from egg to
      metamorph ranged from 0.01 in 2008 to 0.09 in 2009 and was not related to minimum
      spring temperatures, metamorph survival probability ranged from 0.13 in 2010-2011
      to 0.86 in 2012-2013 and was positively related to mean monthly temperatures
      (logit-scale slope = 2.37), adult survival probability was lower for founders
      (0.40) than individuals recruited after reintroduction (0.56), and the mean
      number of egg masses per adult female was 0.74. Our study is the first to test
      hypotheses concerning Oregon spotted frog egg-to-metamorph and metamorph-to-adult
      transition probabilities in the wild and document their response at multiple life
      stages following reintroduction. Furthermore, we provide an example to illustrate
      how the structure of our integrated population model serves as a useful
      foundation for amphibian decision-support models within adaptive management
      programs. The integration of multiple, but related, data sets has an advantage of
      being able to estimate complex ecological relationships across multiple life
      stages, offering a modeling framework that accommodates uncertainty, enforces
      parsimony, and ensures all model parameters can be confronted with monitoring
      data.

PMID- 28452417
TI  - Crack-Free, Soft Wrinkles Enable Switchable Anisotropic Wetting.
AB  - Soft skin layers on elastomeric substrates are demonstrated to support mechano
      responsive wrinkle patterns that do not exhibit cracking under applied strain.
      Soft fluoropolymer skin layers on pre-strained poly(dimethylsiloxane) slabs
      achieved crack-free surface wrinkling at high strain regimes not possible by
      using conventional stiff skin layers. A side-by-side comparison between the soft
      and hard skin layers after multiple cycles of stretching and releasing revealed
      that the soft skin layer enabled dynamic control over wrinkle topography without
      cracks or delamination. We systematically characterized the evolution of wrinkle
      wavelength, amplitude, and orientation as a function of tensile strain to resolve
      the crack-free structural transformation. We demonstrated that wrinkled surfaces
      can guide water spreading along wrinkle orientation, and hence switchable,
      anisotropic wetting was realized.

PMID- 28452416
TI  - Low CREBBP expression is associated with adverse long-term outcomes in paediatric
      acute lymphoblastic leukaemia.
AB  - OBJECTIVES: CREBBP alterations are associated with many diseases including
      leukaemia. However, CREBBP expression and its clinical relevance in paediatric
      acute lymphoblastic leukaemia have not been elucidated. METHODS: We studied
      CREBBP mRNA expression in 349 patients treated with either the BCH-2003 or CCLG
      2008 protocol. Using a receiver operating characteristic curve, patients were
      divided into low- or high-CREBBP. The association among clinicobiological
      characteristics, outcomes and CREBBP level was analysed. RESULTS: Low expression
      of CREBBP (<1.0) at diagnosis was found in 97.7% of patients and increased
      significantly after complete remission. Low-CREBBP patients were associated with
      unfavourable clinical presentations, poor prednisone response and high minimal
      residual disease (>10-2 ) after induction. We found significantly poorer event
      free survival (EFS) and overall survival (OS) in low-CREBBP group whether
      administered BCH-2003 or CCLG-2008. Low-CREBBP was an inferior independent
      prognostic factor in BCH-2003; patients with low-CREBBP had better outcomes on an
      intermediate-risk regimen than a standard-risk regimen involving the CCLG-2008
      protocol. Patients stratified to high-risk with low-CREBBP had the worst EFS and
      OS. CONCLUSIONS: These findings indicate that low-CREBBP is predictive of
      unfavourable outcomes; thus, a more intensive treatment protocol is necessitated
      for standard-risk patients with insufficient CREBBP and that a specific target
      therapy is necessitated for high-risk patients.

PMID- 28452418
TI  - Does psychosocial stress explain socioeconomic inequities in 9-year weight gain
      among young women?
AB  - OBJECTIVE: This study investigated the contribution of psychosocial stress to
      mediating inequities in weight gain by educational status in a large cohort of
      young Australian women over a 9-year follow-up. METHODS: This observational
      cohort study used survey data drawn from 4,806 women, aged 22 to 27 years at
      baseline (2000), participating in the Australian Longitudinal Study on Women's
      Health, who reported their education level (2000), perceived stress (2003), and
      weight (2003 and 2012). Using a causal inference framework based on
      counterfactuals for mediation analysis, we fitted linear or logistic regression
      models to examine the total effect, decomposed into natural direct and indirect
      effects via perceived stress, of education level (highest qualification
      completed: up to year 12/trade or diploma vs. university) on weight change.
      RESULTS: Women with lower education gained more weight over 9 years (6.1 kg,
      standard deviation [SD] 9.5) than women with higher education (3.8 kg, SD 7.7; P
      < 0.0001) and were more likely to be very or extremely stressed. The higher
      weight gain associated with low education was not mediated through perceived
      stress (per SD increase, percent mediated: 1.0%). CONCLUSIONS: Education-based
      inequities in weight gain over time were not attributable to greater psychosocial
      stress among women with lower education levels.

PMID- 28452420
TI  - Neurobehavioural and cognitive development in infants born to mothers with eating
      disorders.
AB  - INTRODUCTION: Although recent research has focused on the effects of maternal
      eating disorders (EDs) on children, little is known about the effect of maternal
      EDs on neurobiological outcomes in newborns and infants. This study is the first
      to investigate neurobehavioural regulation and cognitive development in newborns
      and infants of mothers with EDs. METHODS: Women with an active and past ED and
      healthy controls were recruited to a prospective longitudinal study during their
      first trimester or second trimester of pregnancy. Newborns and infants of mothers
      with ED were compared with newborns and infants of healthy controls on (a)
      neurobehavioural dysregulation using the Brazelton Neonatal Behavioural
      Assessment Scale at 8 days postpartum (active ED, n = 15; past ED, n = 20;
      healthy controls, n = 28); and (b) cognitive development using the Bayley Scales
      of Infant and Toddler Development at 1-year postpartum (active ED, n = 18; past
      ED, n = 19; healthy controls, n = 28). In order to maintain the largest possible
      sample at each time point, sample size varied across time points. RESULTS:
      Newborns of mothers with an active ED had worse autonomic stability when compared
      with newborns of healthy controls [B = -0.34 (-1.81, -0.26)]. Infants of mothers
      with a past ED had poorer language [B = -0.33 (-13.6, -1.9)] and motor
      development [B = -0.32 (-18.4, -1.3)] compared with healthy controls.
      CONCLUSIONS: Children of mothers with ED display neurobehavioural dysregulation
      early after birth and poorer language and motor development at 1 year. These
      characteristics suggest evidence of early neurobiological markers in children at
      risk. Differential outcomes in children of women with active versus past ED
      suggest that active symptomatology during pregnancy might have an effect on
      physiological reactivity while cognitive characteristics might be more stable
      markers of risk for ED.

PMID- 28452421
TI  - Paroxysmal nocturnal hemoglobinuria clones are not infrequent in patients with
      inherited bone marrow failure syndromes.

PMID- 28452419
TI  - Neurosteroid-sensitive delta-GABAA receptors: A role in epileptogenesis?
AB  - OBJECTIVE: We determined the role of the neurosteroid-sensitive delta subunit
      containing gamma-aminobutyric acid A receptors (delta-GABARs) in epileptogenesis.
      METHODS: Status epilepticus (SE) was induced via lithium pilocarpine in adult
      rats, and seizures were assessed by continuous video-electroencephalography (EEG)
      monitoring. Finasteride was administered to inhibit neurosteroid synthesis. The
      total and surface protein expression of hippocampal delta, alpha4, and gamma2
      GABAR subunits was studied using biotinylation assays and Western blotting.
      Neurosteroid potentiation of the tonic currents of dentate granule cells (DGCs)
      was measured by whole-cell patch-clamp technique. Finally, the effects of
      inhibiting N-methyl-d-aspartate receptors (NMDARs) during SE on the long-term
      plasticity of delta-GABARs, neurosteroid-induced modulation of tonic current, and
      epileptogenesis were studied. RESULTS: The inhibition of neurosteroid synthesis 4
      days after SE triggered acute seizures and accelerated the onset of chronic
      recurrent spontaneous seizures (epilepsy). The down-regulation of neurosteroid
      sensitive delta-GABARs occurred prior to the onset of epilepsy, whereas an
      increased expression of the gamma2-GABAR subunits occurred after seizure onset.
      MK801 blockade of NMDARs during SE preserved the expression of neurosteroid
      sensitive delta-GABARs. NMDAR blockade during SE also prevented the onset of
      spontaneous seizures. SIGNIFICANCE: Changes in neurosteroid-sensitive delta-GABAR
      expression correlated temporally with epileptogenesis. These findings raise the
      possibility that delta-GABAR plasticity may play a role in epileptogenesis.

PMID- 28452422
TI  - Cobalt-Catalyzed Alkylation of Secondary Alcohols with Primary Alcohols via
      Borrowing Hydrogen/Hydrogen Autotransfer.
AB  - Alcohols are promising sustainable starting materials because they can be
      obtained from abundant and indigestible biomass. The substitution of expensive
      noble metals in catalysis by earth abundant 3d metals, such as Mn, Fe, or Co,
      (nonprecious or base metals) is a related key concept with respect to
      sustainability. Here, we report on the first cobalt-catalyzed alkylation of
      secondary alcohols with primary alcohols. Easy-to-synthesize and easy-to-activate
      PN5 P-pincer-ligand-stabilized Co complexes developed in our laboratory mediate
      the reaction most efficiently. The catalysis is applicable to a broad substrate
      scope and proceeds under relatively mild conditions. We have even demonstrated
      the coupling of a variety of purely aliphatic alcohols with a base or nonprecious
      metal catalyst. Mechanistic studies indicate that the reaction follows the
      borrowing hydrogen or hydrogen autotransfer concept.

PMID- 28452423
TI  - Coccidioidomycosis among persons undergoing lung transplantation in the
      coccidioidal endemic region.
AB  - BACKGROUND: Coccidioidomycosis, an endemic fungal infection, is more likely to be
      symptomatic and severe among those receiving allogeneic transplants. While
      several case series have been published for various transplanted organs, none has
      described the incidence and outcomes in those receiving lung transplants within
      the coccidioidal endemic region. METHODS: Patients receiving a heart-lung, single
      lung, or bilateral-lung transplantation at the University of Arizona between 1985
      and 2009 were retrospectively reviewed. RESULTS: Coccidioidomycosis occurred post
      transplantation in 11 (5.8%) of 189 patients. All but one patient was diagnosed
      with pulmonary coccidioidomycosis and only one had a history of prior
      coccidioidomycosis. Two patients received transplants from donors found to have
      coccidioidomycosis at the time of transplantation and one death was directly
      attributed to coccidioidomycosis. The risk of developing active
      coccidioidomycosis was significantly higher if the patient did not receive some
      type of antifungal therapy post transplantation (P<.001). CONCLUSION: Within the
      coccidioidal endemic region, post-transplantation coccidioidomycosis was a
      definable risk among lung transplant recipients. Use of antifungals appeared to
      reduce this incidence of disease. Almost all cases resulted in pulmonary disease,
      suggesting that the lung is the primary site of infection.

PMID- 28452425
TI  - DECHEMA Prize: R. Palkovits / DECHEMA Early-Career Prize: T. Magauer / Merck
      Banyu Lectureship Award: T. Ogoshi.

PMID- 28452424
TI  - Benchmarking Quantum Chemical Methods: Are We Heading in the Right Direction?
AB  - Theoreticians and experimentalists should work together more closely to establish
      reliable rankings and benchmarks for quantum chemical methods. Comparison to
      carefully designed experimental benchmark data should be a priority. Guidelines
      to improve the situation for experiments and calculations are proposed.

PMID- 28452426
TI  - Aerobic respiration by haemocyanin in the embryo of the migratory locust.
AB  - It remains unresolved how insect embryos acquire sufficient oxygen to sustain
      high rates of respiratory metabolism during embryogenesis in the absence of a
      fully developed tracheal system. Our previous work showed that the two distinct
      subunits (Hc1 and Hc2) of haemocyanin (Hc), a copper-containing protein, display
      embryo-specific high expression that is essential for embryonic development and
      survival in the migratory locust Locusta migratoria. Here we investigated the
      role of haemocyanins in oxygen sensing and supply in the embryo of this locust.
      Putative binding sites for hypoxia-regulated transcription factors were
      identified in the promoter region of all of the Hc1 and Hc2 genes. Embryonic
      expression of haemocyanins was highly upregulated by ambient O2 deprivation, up
      to 10-fold at 13% O2 content. The degree of upregulation of haemocyanins
      increased with increasing levels of hypoxia. Compared with low-altitude locusts,
      embryonic expression of haemocyanins in high-altitude locusts from Tibetan
      plateau was constitutively higher and more robust to oxygen deprivation. These
      findings strongly suggest an active involvement of haemocyanins in oxygen
      exchange in embryos. We thus propose a mechanistic model for embryo respiration
      in which haemocyanin plays a key role by complementing the tracheal system for
      oxygen transport during embryogenesis.

PMID- 28452427
TI  - Results of an innovative bulking agent in patients with stress urinary
      incontinence who are not optimal candidates for mid-urethral sling surgery.
AB  - AIMS: To assess the efficacy and safety of peri-urethral bulking injections (PBI)
      with an innovative bulking material (PDMS-U) in women with stress-urinary
      incontinence (SUI) who are not optimal candidates for mid-urethral sling surgery.
      METHODS: A prospective study was performed in women with SUI who, for several
      reasons, have a relative contraindication for a mid-urethral sling procedure.
      These reasons include: (i) recurrent SUI after a prior SUI surgical procedure;
      (ii) a history of oncologic gynaecological surgery; (iii) a history of neurologic
      disease resulting in voiding problems; (iv) a maximal flow rate of less than 15
      mL per second or; (v) women with a contraindication for surgery with general or
      regional anaesthesia. All women were treated with PBI consisting of PDMS-U, a
      bulking agent that polymerizes in situ. The primary outcome was subjective
      improvement, defined as "a little better" to "very much better" on the PGI-I.
      Secondary outcomes included objective cure, disease specific quality of life and
      adverse events. RESULTS: Subjective improvement was reported by 18 (90%) of the
      20 included patients. The subjective cure rate was 56% and the objective cure
      rate was 65%. There was a statistically significant improvement of all domain
      scores of the UDI-6, IIQ-7, and PISQ-12 at 6 months follow up. Abnormal post
      voiding residual volume (>150 mL) was the most common adverse event (40%), but
      persisted in only one patient, based on the patient's preference for a catheter.
      CONCLUSIONS: PBI with PDMS-U is a viable treatment option in women with a
      relative contra-indication for mid-urethral sling surgery.

PMID- 28452428
TI  - Impact of gluten consumption in patients with functional dyspepsia: A case
      control study.
AB  - BACKGROUND AND AIM: Dietary factors and immune dysfunction may induce symptoms in
      patients with functional dyspepsia (FD). The aim of the study was to evaluate
      whether gluten consumption impacts symptom onset in patients with FD and to
      evaluate for possible histologic alterations in the duodenum of patients with FD.
      METHODS: We prospectively enrolled 101 patients newly diagnosed with FD and 31
      asymptomatic controls. Specific FD symptoms and gluten consumption patterns were
      evaluated by self-reported questionnaires. Tight junction protein (claudin-1)
      expression and presence of intraepithelial lymphocyte (IEL) infiltration in the
      bulb (D1) and second portion (D2) of the duodenum were assessed by
      immunohistochemistry. RESULTS: Wheat bun consumption had higher frequency (P =
      0.047) and increased average consumption (P = 0.01) scores in patients with FD
      compared with the control group. Of the 101 patients with FD, early satiety (P =
      0.03) was associated with increased wheat bun consumption frequency score. On
      histologic evaluation, claudin-1 expression was decreased in D1 (0.003 +/- 0.001
      vs 0.012 +/- 0.002, P = 0.003) and D2 (0.002 +/- 0.0004 vs 0.012 +/- 0.001, P <
      0.001), while duodenal IEL counts were increased in D1 (15.5 +/- 7.8 vs 3.1 +/-
      2.5, P < 0.001) and D2 (20.6 +/- 7.7 vs 5.8 +/- 3.4, P < 0.001) among patients
      with FD compared with the control group. Finally, Helicobacter pylori infection
      was associated with increased IELs in D1 (20.6 +/- 7.0 vs 14.2 +/- 7.4, P =
      0.001) among patients with FD. CONCLUSIONS: Among patients with FD, gluten-rich
      food may lead to symptom onset, specifically early satiety. Intestinal epithelial
      barrier dysfunction characterized by decreased claudin-1 expression and mucosal
      immune activation demonstrated by IEL infiltration may contribute to the
      pathogenesis of FD.

PMID- 28452430
TI  - Remote Monitoring of Daily Nocturnal Hemodialysis.
AB  - Daily nocturnal hemodialysis (DNHD) is a new variant of home hemodialysis that
      allows patients to dialyze at home, at night, while they sleep, providing longer
      duration and greater frequency of treatments. This paper describes a 3-year
      experience with remote monitoring of DNHD patients over the Internet, and we
      review the remote monitoring experience of the Toronto program, which pioneered
      DNHD. Technology, structure, and costs are reviewed. Remote monitoring enhanced
      safety, accuracy of data collection, patient catchment area, and the overall
      comfort of patients, providers, and regulators.

PMID- 28452429
TI  - Metabolomic profiling distinction of human nonalcoholic fatty liver disease
      progression from a common rat model.
AB  - OBJECTIVE: Characteristic pathological changes define the progression of
      steatosis to nonalcoholic steatohepatitis (NASH) and are correlated to metabolic
      pathways. A common rodent model of NASH is the methionine and choline deficient
      (MCD) diet. The objective of this study was to perform full metabolomic analyses
      on liver samples to determine which pathways are altered most pronouncedly in
      this condition in humans, and to compare these changes to rodent models of
      nonalcoholic fatty liver disease (NAFLD). METHODS: A principal component analysis
      for all 91 metabolites measured indicated that metabolome perturbation is greater
      and less varied for humans than for rodents. RESULTS: Metabolome changes in human
      and rat NAFLD were greatest for the amino acid and bile acid metabolite families
      (e.g., asparagine, citrulline, gamma-aminobutyric acid, lysine); although, in
      many cases, the trends were reversed when compared between species (cholic acid,
      betaine). CONCLUSIONS: Overall, these results indicate that metabolites of
      specific pathways may be useful biomarkers for NASH progression, although these
      markers may not correspond to rodent NASH models. The MCD model may be useful
      when studying certain end points of NASH; however, the metabolomics results
      indicate important differences between humans and rodents in the biochemical
      pathogenesis of the disease.

PMID- 28452431
TI  - Tunneled Catheter-Associated Atrial Thrombi: Successful Treatment with Chronic
      Anticoagulation.
AB  - Tunneled dialysis catheter-associated right atrial thrombus (RAT) is a rarely
      reported complication. We reviewed hospital records of 10 patients from a
      teaching hospital dialysis unit, in whom RAT was diagnosed by trans-esophageal
      echocardiography (TEE). Patients were treated with chronic anticoagulation
      (heparin followed by warfarin) and followed over time. The group included 7
      women; 6 patients were African American, 3 were Caucasian, and 1 was Hispanic.
      The average age was 52.1 +/- 15.3 years. The most common presenting symptom was
      poor catheter flow on hemodialysis followed by fever and chills. On average, the
      patients had had 3.4 +/- 2.7 catheter insertions before diagnosis of RAT, and the
      tunneled dialysis catheter (TC) had been in place for a mean of 91 +/- 89.4 days
      when the thrombi were diagnosed. Trans-thoracic echocardiography (2-D echo) was
      done in 4 patients, but it identified RAT in only 1 patient. The catheter tip was
      at the junction of the superior vena cava and right atrium (SVC/RA) in most
      patients. Thrombolysis (unsuccessful) was attempted with urokinase in 3 patients,
      complicated in 2 patients by hemorrhage. After anticoagulation, 90% of the RAT
      resolved on repeated TEE. One patient had persistent RAT for 23 weeks and
      underwent surgical thrombolysis, but died postoperatively. We conclude that RAT
      is a frequently missed complication of a TC. Positioning the tip of the TC at the
      SVC/RA junction may not prevent RAT. Trans-esophageal echocardiography is a more
      sensitive diagnostic tool than 2-D echo and should be obtained early. Most
      patients can be successfully treated with anticoagulation alone. Thrombolytic
      therapy and surgical thrombolysis have high morbidity and mortality.

PMID- 28452432
TI  - Clinical Determination of Dry Body Weight.
AB  - While nephrologists wait for the ideal, non invasive, inexpensive, precise, and
      reproducible tool to evaluate extracellular volume (ECV), they need to exert
      their clinical acumen in the quest of that holy grail, dry weight (DW).
      Estimation of DW using a clinical approach based on blood pressure (BP) and ECV
      is feasible and reliable as shown by successful experiences in various dialysis
      modes over more than three decades. But a need still exists to resolve
      difficulties associated with accurate assessment of BP (methods and circumstances
      of measurement, and the confounding effects of antihypertensive drugs) and ECV
      (evaluation of weight changes unrelated to ECV, lack of specificity and
      sensitivity of clinical symptoms, lag time, confusion in terminology). An
      essential point in clinical assessment of DW is that a normal BP is at the same
      time the target and the crucial index of DW achievement. For this reason, a
      trialand-error "probe" process has to be used at intervals to make sure that the
      dry weight target point is correctly estimated. The various "non clinical"
      methods proposed for dry weight assessment increase the complexity and the cost
      of hemodialysis. They are, in the present state of things, more clinical research
      than practice tools. They do not replace clinical judgment.

PMID- 28452433
TI  - Daily Dialysis and Flexible Schedules: How to Assess Kt/V and EKRc ?
AB  - Despite the growing interest in daily hemodialysis (DHD), logistic and economic
      factors limit its dissemination. Not the least of these factors is the lack of
      uniform criteria for measuring efficiency. From November 1998 to November 2000,
      19 patients were on DHD in our unit. The dialysis prescription was bicarbonate
      buffer; 6 sessions per week; 2 - 3 hours; blood flow 250 - 350 mL/min; individual
      K, HCO3 , and Na levels; membrane 1.6 - 2 m2 (polysulfone, polycarbonate). The
      prescription represented the minimum dialysis requirement; patients were free to
      add up to 30 minutes per session, further increase or any decreases needed
      confirmation by the caregivers. The aim of the study was to assess Kt/Vurea
      variability in this clinical setting, and to identify the minimum number of
      dialysis sessions required to obtain a reliable estimate of weekly Kt/Vurea
      [relative error (RE) < 10%]. We studied 169 dialysis sessions in 13 clinically
      stable patients on DHD for >= 3 months, with >= 3 Kt/Vurea measurements within 2
      weeks (median: 10; range: 3 - 32 sessions), tested in the same laboratory. To
      assess variability, we employed the simplest formula (the Lowrie Kt/Vurea ), the
      widely used Daugirdas II formula, and the derived single-pool equivalent renal
      clearance (EKRc ), according to Casino. The variability of Kt/Vurea per session
      was high (Lowrie: RE = 2.5% - 22.1%; Daugirdas II and EKRc : RE = 3.6% - 24%).
      Averaging several dialysis sessions leads to a more reliable estimate of weekly
      efficiency (6 sessions: RE = 0; 3 sessions, Lowrie formula: Kt/Vurea RE = 1.1% -
      9.7%; Daugirdas II and EKRc : RE = 1.6% - 10.6%). In patients with wide time
      variations, variability may be lower if weekly efficiency is determined on the
      basis of "average hourly Kt/Vurea ," which is calculated by dividing Kt/Vurea by
      the number of hours in the studied sessions, and then multiplying by the hours of
      dialysis performed in the whole week (Lowrie formula, Kt/Vurea : RE = 4.8% -
      16.6% for 1 session, 2.1% - 7.3% for 3 sessions). Once again, the RE decreases
      sharply when data from 3 sessions are considered. Therefore, for flexible DHD, we
      suggest averaging the data from >= 3 sessions for weekly Kt/Vurea assessment.

PMID- 28452434
TI  - Pathophysiology and Treatment of Hyperhomocysteinemia in End-Stage Renal Disease
      Patients.
AB  - The pathophysiology of hyperhomocysteinemia in end-stage renal disease (ESRD)
      patients includes impaired remethylation of homocysteine (Hcy) to methionine,
      inhibition of extrarenal Hcy metabolism by uremic solutes, a block in
      decarboxylation of cysteinesulfinic acid, impaired
      [adenosylmethionine]/[adenosylhomocysteine] ratio, and a probable impairment of
      renal Hcy metabolism and excretion. Treatment of hyperhomocysteinemia in ESRD
      patients includes administration of folic acid (1 - 15 mg per day). No additional
      effects have been observed with higher folic acid doses, folinic acid, or 5
      methyltetrahydrofolate. Oral supplementation with vitamin B 6 and vitamin B 12
      has no effect, but some studies reported a decrease of plasma Hcy with high
      intravenous vitamin doses. Effective reduction of plasma total Hcy (tHcy) in
      patients treated with super-flux hemodialyzers suggests the removal of uremic
      toxins with inhibitory activities against enzymes involved in the extrarenal Hcy
      metabolism.

PMID- 28452435
TI  - Peritoneal Dialysis and Hemodialysis in Pregnancy.
AB  - Management of women who require dialysis during pregnancy is an unusual and
      challenging clinical problem for both the nephrologist and the obstetrician. More
      than 200 pregnancies have been reported in women requiring hemodialysis, and more
      than 50 pregnancies in women on peritoneal dialysis. Surveys from several
      countries of pregnancy in dialysis patients provide data regarding management and
      outcomes. Conception rates are significantly lower in women on dialysis, and when
      these women do become pregnant, the spontaneous abortion rate usually exceeds
      40%. However, in the pregnancies that continue, as many as 71% result in
      surviving infants. Pregnant women require longer, more intense hemodialysis, and
      enough experience has been reported to support the use of peritoneal dialysis as
      well as hemodialysis during pregnancy. The patients typically experience anemia,
      hypertension, and premature delivery. Most infants are small for gestational age,
      and the stillbirth rate is as high as 12%. While the potential problems are many,
      sufficient data has been accumulated to provide clinicians with guidelines to
      help them manage pregnant women on dialysis and to achieve successful outcomes.

PMID- 28452437
TI  - Tribute Given to Professor Robin Eady on His 60th Birthday.

PMID- 28452436
TI  - Surgical Revision and Early Cannulation of the Arteriovenous Fistula in
      Hemodialysis Patients: An Effective Technique.
AB  - Arteriovenous fistula (AVF) dysfunction is a common problem in hemodialysis
      patients. After surgical revision for malfunction, we used AVFs early to avoid
      complications associated with central venous catheters. In this study, we report
      experience with surgical revisions of native AVFs with suspected arterial
      dysfunction as the cause of inadequate arterial inflow for dialysis. Exclusion
      criteria were presence of a central venous catheter as a hemodialysis access, and
      clinical or radiologic evidence of stenosis or thrombosis of the distal venous
      segment of the AVF. We prospectively studied 50 patients (mean age 60.2 +/- 10.5
      years, 25 men and 25 women) with 59 revisions. The patients were followed until
      change in the modality of dialysis, transplant, or death. The types of AVFs
      revised were left wrist radiocephalic in 27 patients (54%), left forearm
      radiocephalic in 10 (20%), right wrist radiocephalic in 6 (12%), left antecubital
      brachiocephalic in 3 (6%), right antecubital brachiocephalic in 2 (4%), and right
      forearm radiocephalic in 2 (4%). The causes of inadequate arterial flow were
      juxta-anastomotic thrombosis in 20 patients (40%), inadequate arterial
      anastomotic flow in 16 (32%), inadequate anastomosis in 7 (14%), and juxta
      anastomotic venous stenosis in 7 (14%). The primary surgical revision techniques
      were proximal neo-anastomosis using the semiarterialized vein in 43 patients
      (86%), thrombectomy and re-anastomosis in 5 (10%), and resection and repair in 2
      (4%). Technical success, defined as successful cannulation of the revised AVF for
      hemodialysis and avoidance of central venous catheter, was achieved in 44 of 50
      patients (88%). Technical failure occurred 6 cases, the causes being inadequate
      arterial flow in 3 patients, failure to cannulate the veins in 2 patients, and
      steal syndrome in 1 patient. After primary revisions failed, 9 re-revisions were
      done in 6 patients. The 1-year, 2-year, and 3-year primary and overall patency
      rates were 76.2%, 67.6%, 65.0%, and 85.7%, 75.7%, 65.0%, respectively. In
      conclusion, surgical salvage of the AVF with inadequate arterial flow is an
      effective approach that can be performed as an outpatient procedure and allows
      early cannulation of the semi-arterialized veins, thus avoiding the use of
      central venous catheters.

PMID- 28452438
TI  - Overview of Blood Coagulation.
AB  - The endothelium is the principal anti-thrombotic mechanism, providing a non
      wettable surface and generating potent vasodilators (nitric oxide and
      prostacyclin) and clotting inhibitors [thrombomodulin and tissue factor pathway
      inhibitor (TFPI)]. When the integrity of the endothelium is breached,
      vasoconstriction occurs through neural and chemical (endothelin, thromboxane)
      mechanisms, and platelet adhesion is facilitated (von Willebrand factor).
      Activation of platelets accompanied by microparticle formation provides a
      thrombogenic surface for subsequent coagulation reactions. The initial generation
      of small amounts of thrombin greatly amplifies subsequent clotting factor
      activation and results in substantial thrombin formation. Thrombin activates an
      inhibitor of fibrinolysis [thrombin activatable fibrinolysis inhibitor (TAFI)]
      which prevents the binding of plasminogen to fibrin. Mechanisms to limit clot
      formation include inhibition of the tissue factor-factor VIIa complex by TFPI,
      inhibition of activated factors V and VIII by activated protein C, and binding of
      thrombin by thrombomodulin, heparin cofactor II, and anti-thrombin. Clot
      dissolution is promoted by plasminogen activators (tissue plasminogen activator
      and urokinase) and by plasminogen.

PMID- 28452439
TI  - Management of Heparin-Induced Thrombocytopenia During Renal Replacement Therapy.
AB  - Awareness is increasing concerning the development of antibodies to heparin
      platelet factor 4 complex in both regular hemodialysis patients and those treated
      with continuous forms of renal replacement therapy. Although the development of
      antibodies does not result in thrombocytopenia or thrombosis in some patients,
      most patients present with thrombocytopenia, premature platelet activation, and
      clotting of the extracorporeal circuit. When systemic anticoagulation is also
      required to treat venous thrombosis, then synthetic heparinoids or recombinant
      hirudin will be the agents of choice. However, neither the synthetic heparinoids
      nor hirudin are without problems. A few patients may have cross-reacting
      antibodies against the currently available heparinoids. Similarly, antibodies may
      develop against recombinant hirudin, leading to a potentiation of anticoagulant
      activity and increased risk of hemorrhage. In the future, thrombin inhibitors
      such as recombinant hirudin and the arginine derivative argatroban will probably
      be the agents most widely used to prevent thromboembolic complications. However,
      anti-platelet agents used alone or in combination with hirudin or synthetic
      heparinoids may provide adequate treatment by inhibiting both platelet and
      clotting cascade activation.

PMID- 28452440
TI  - Dialysis Disequilibrium Syndrome Revisited.
AB  - An aggressive dialysis in a grossly azotemic patient, especially one with severe
      metabolic acidosis, can lead to dialysis disequilibrium syndrome (DDS). Mild
      forms present as nausea, vomiting, restlessness, and headache. Severe
      manifestations include seizures, obtundation, coma, and even death. This clinical
      picture is caused by cerebral edema induced by one or more of the following
      mechanisms: "Reverse urea effect" - Dialysis removes urea faster from the blood
      than from the brain; consequently, water enters the brain. "Cerebrospinal fluid
      acidosis" - Correction of systemic acidosis engenders the condition due to a
      lowering of brain pH. "Idiogenic osmoles" - As a response to blood hyperosmolar
      state, osmoles are produced in the brain. As blood osmolality decreases under
      relatively quick dialysis, idiogenic osmoles tend to induce brain edema. Because
      the symptoms of DDS can be life-threatening, preventive measures in patients with
      severe uremia are important. The first strategy relies on raising blood
      osmolality by introducing solutes (osmoles) into the blood. The second approach,
      which is the most common, decreases the efficiency of the dialysis treatment by
      shortening the duration of a dialysis run to 25% - 30% of normal, by lowering
      dialyzer blood flow or dialysate flow rate, by using a less efficient dialyzer,
      or by a combination of these maneuvers. Dialysis frequency is increased instead.
      Anticonvulsant drugs are needed in cases where the preventive measures have not
      been used or have been unsuccessful.

PMID- 28452441
TI  - Mechanism and Clinical Presentation of Heparin-Induced Thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening
      complication of heparin anticoagulation, occurring in approximately 3% of
      patients treated with unfractionated heparin. Heparin and platelet factor 4 (PF4)
      are capable of forming multimolecular complexes. Given stoichiometric
      concentrations of heparin and platelet factor 4 (PF4), heparin may induce
      conformational changes in the PF4 molecule, rendering it antigenic. The
      subsequent immune response generates antibodies against heparin-PF4 complexes
      (HIT antibodies). Binding of these antibodies to FcgammaIIA receptors on the
      surface of platelets results in potent platelet activation. Binding of HIT
      antibodies to heparan sulfate-PF4 complexes on the surface of endothelial cells
      (ECs) causes EC activation with subsequent expression of tissue factor.
      Activation of platelets and of ECs together leads to marked thrombin generation,
      resulting in the hypercoagulable state in HIT. Clinically, HIT presents with two
      major sequelae: thrombocytopenia and thrombosis. Thrombocytopenia-that is, a
      platelet count below 150*10 9 /L-is present in 85% - 90% of HIT patients and
      typically occurs between day 5 and day 10 of heparin treatment. The mean platelet
      count nadir is approximately 60*10 9 /L. Alternatively, HIT may be associated
      with a marked fall in platelet count (>=50% of the initial value) whose nadir is
      not below 150*10 9 /L. Despite the low platelet count, thrombosis rather than
      bleeding predominates. In HIT, the risk for thrombosis is 5% - 10% in the first 2
      days; the 30-day cumulative risk is approximately 50%. Thromboses most often
      occur in deep veins of the lower limbs, frequently leading to pulmonary embolism.
      If thrombosis is severe or if it is detected in an unusual location in
      heparintreated patients, HIT should be suspected.

PMID- 28452442
TI  - Laudatio: Dr. Bernard Charra.

PMID- 28452444
TI  - Update on the International Society for Hemodialysis (ISHD).

PMID- 28452443
TI  - Normalization of Dialysis Dose for Daily Dialysis.
AB  - The equilibrated Kt/V (eKtV) is widely used in hemodialysis (HD) as a measure of
      the intensity (magnitude) of an individual dialysis treatment. Adequate eKt/V for
      thrice-weekly hemodialysis (twHD) has been extensively studied, and a value in
      the range 1.0 - 1.1 per treatment (3.0 - 3.3 weekly) is generally considered to
      represent adequate therapy for this specific frequency of dialysis. However, for
      other schedules, summing eKt/V's and time-averaging the clearance is not
      appropriate. This was first demonstrated several years ago by the observation
      that a weekly eKt/V of 2.0 in continuous ambulatory peritoneal dialysis (CAPD) is
      therapeutically equal to a weekly eKt/V of 3.0 in twHD. That paradox has been
      resolved by the standard Kt/V (stdKt/V), which accounts for the first order
      nature of solute removal by dialysis, and which correctly predicts a normalized
      weekly stdKt/V of 2.0 for both CAPD and twHD. The equivalent renal clearance
      (EKR) has also been advanced as a method to normalize dose for varying treatment
      schedules. However, mathematical consideration shows that EKR is an exact time
      averaged clearance. Analysis of data reported for daily dialysis by Piccoli et
      al. in the present issue of Hemodialysis International shows that the EKRc t/V
      calculated for daily dialysis is identical to the sum of eKt/V's for the
      individual dialyses. We therefore conclude that EKR is not a suitable parameter
      for normalizing the dialysis dose, because it fails to reflect the effect of
      dialysis frequency in HD therapy.

PMID- 28452445
TI  - The Clinical Impact of Increasing the Hemodialysis Dose.
AB  - Good evidence suggests that improvements in dialysis efficiency reduce morbidity
      and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been
      related to better control of arterial blood pressure (BP), anemia, and serum
      phosphorus levels, and to improvement in patients' nutritional status. Over a 2
      year period, the present self-controlled study of 34 HD patients (23 men, 11
      women; age, 52.6 +/- 14.5 years; HD duration, 55.9 +/- 61.2 months) looked at the
      effect on clinical and laboratory parameters of increasing the delivered dialysis
      dose under a strict dry-weight policy. Dialysis dose was increased without
      increasing dialysis time and frequency. A statistically significant increase was
      seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% +/-
      10% from 52% +/- 8%, and then to 71% +/- 7% (p < 0.001); Kt/Vurea increased to
      1.22 +/- 0.28 from 0.93 +/- 0.19, and then to 1.55 +/- 0.29 (p < 0.001). A
      statistically significant increase in hemoglobin concentration also occurred-to
      10.8 +/- 1.9 g/dL from 10.4 +/- 1.7 g/dL, and then to 11.0 +/- 1.3 g/dL (p < 0.05
      as compared to baseline)-with no significant difference in weekly erythropoietin
      dose. Statistically significant decreases occurred in the systolic and diastolic
      blood pressures during the first year; they then remained unchanged. Systolic
      blood pressure decreased to 131 +/- 23 mmHg from 147 +/- 24 mmHg (p < 0.001);
      diastolic blood pressure decreased to 65 +/- 11 mmHg from 73 +/- 12 mmHg (p <
      0.001). Serum albumin increased insignificantly to 4.4 +/- 0.4 g/dL from 4.3 +/-
      0.4 g/dL, and then significantly to 4.6 +/- 0.3 g/dL (p = 0.002 as compared to
      both previous values). Normalized protein catabolic rate increased significantly
      to 1.16 +/- 0.15 g/kg/day from 0.93 +/- 0.16 g/kg/ day (p < 0.001), and then to
      1.20 +/- 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the
      increases achieved in average Kt/Vurea per hemodialysis session by increasing
      dialyzer membrane area, and blood and dialysate flows, without increasing
      dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with
      strict dry-weight policy, resulted in improvements in hypertension, nutritional
      status, and anemia.

PMID- 28452446
TI  - A Comparative Study of C-Reactive Protein Plasma Levels in Patients on
      Hemodialysis and Peritoneal Dialysis.
AB  - In dialysis patients, C-reactive protein (CRP), a well-recognized marker of
      inflammation, predicts mortality. Higher levels have been described in
      hemodialysis (HD) patients as compared with peritoneal dialysis (PD) patients.
      Our aim was to determine, based on CRP plasma levels, the degree of inflammation
      in HD patients using low-permeability polysulfone membranes and relatively pure
      dialysate, and that in PD patients. A secondary objective was to study factors
      associated with hypoalbuminemia and inflammation in both populations. We studied
      69 stable patients on dialysis (32 on HD and 37 on PD). The mean age was 69.9 +/-
      8.2 years, and the mean time on dialysis was 27 months. The two populations were
      comparable for overall and cardiovascular comorbidities. Nephelometry was used to
      measure CRP plasma levels (normal levels < 0.6 mg/dL). The Kt/Vurea , corrected
      for residual renal clearance, and the equivalent of protein nitrogen appearance
      (PNA) were also calculated. Of the patients studied, 53% showed CRP plasma levels
      higher than 0.6 mg/dL; in 36%, the levels were higher than 1 mg/dL. No
      significant differences in these percentages were noted between the two dialysis
      groups. Patients with CRP levels higher than 1 mg/dL showed lower serum albumin,
      iron, hemoglobin, and transferrin levels, and higher ferritin values and
      leukocyte counts. Under logistic regression analysis, CRP levels higher and lower
      than 1 mg/dL were significantly associated with serum albumin [p = 0.01; odds
      ratio (OR): 0.15], iron (p = 0.006; OR: 0.96), transferrin (p = 0.004; OR: 0.97),
      and hemoglobin (p = 0.02; OR: 0.67). Serum albumin levels were significantly
      lower in PD patients. Under regression analysis, serum albumin levels correlated
      with cholesterol (r: 0.25; p = 0.04), serum iron (r: 0.5; p = 0.0001),
      transferrin (r: 0.3; p = 0.015), ultrafiltration capacity (r: 0.42; p = 0.008),
      and CRP values above 0.6 mg/dL (r: -0.65; p = 0.001). In conclusion, the frequent
      elevation of CRP plasma levels observed in both HD and PD patients suggests the
      presence of a silent inflammatory state. Hemodialysis performed with
      biocompatible, low-permeability membranes is not associated with higher CRP
      plasma levels than those seen in PD. In both groups, hypoalbuminemia is related
      to CRP level. Levels of serum albumin, slightly lower in PD patients, are also
      related to peritoneal ultrafiltration capacity.

PMID- 28452447
TI  - Arterial Hypertension Is Associated with Increased Serum Lipoprotein(a) Levels in
      End-Stage Renal Disease Patients.
AB  - In addition to disorders in lipoprotein metabolism, several other factors are
      involved in the development of atherosclerotic changes in end-stage renal disease
      (ESRD) patients. One of these is arterial hypertension. We evaluated serum lipids
      total cholesterol (TC), triglycerides (TG), apolipoproteins (AI , A II , B, E),
      lipoprotein(a) [Lp(a)]-in 109 ESRD patients on dialysis [46 on hemodialysis (HD);
      63 on continuous ambulatory peritoneal dialysis (CAPD)] and in 45 hyperlipidemic
      patients without renal failure (HL group). Dialysis patients were divided in two
      groups. Group A included 42 hypertensive patients (mean age: 62.3 +/- 15.5 years)
      whose blood pressure (BP) was satisfactorily controlled with anti-hypertensive
      medications. Group B included 67 non hypertensive patients (mean age: 66.6 +/-
      11.9 years). Levels of Lp(a) were significantly higher in both the HD (p = 0.001)
      and the CAPD (p < 0.05) patients as compared with the HL group. When the HD and
      CAPD groups were divided into hypertensive and non hypertensive patients, Lp(a)
      levels were significantly higher in the hypertensive patients; this difference
      was not observed among non renal failure patients. These results indicate that
      arterial hypertension is associated with elevated Lp(a) serum levels in ESRD
      patients undergoing either HD or CAPD.

PMID- 28452448
TI  - The Progression of Uremic Polyneuropathy in Patients on Hemodialysis and
      Hemofiltration: A Two-Year Study.
AB  - Uremic polyneuropathy is one of the major complications of long-term end-stage
      renal disease. In the present study, we performed an electrophysiologic
      evaluation in 17 patients having a mean age of 49 +/- 11 years. The patients were
      divided into two groups according to dialysis method. Group A included 9 patients
      who were undergoing conventional hemodialysis (mean age, 44.2 +/- 12.5 years;
      mean duration on dialysis, 21.7 +/- 4.3 months); group B included 8 patients
      undergoing hemofiltration (mean age, 55.2 +/- 5.2 years; mean duration on
      treatment, 27 +/- 7.6 months). Measurements of the distal latency time of the
      sensory fibers (median, ulnar, and sural nerves), and measurements of the distal
      latency time and peripheral conduction velocity of the motor fibers (median and
      peroneal nerves) were performed. In addition, we recorded somatosensory evoked
      potentials after peripheral stimulation of the median and peroneal nerves. The
      electrophysiologic evaluations were repeated two times at intervals of 12 months.
      In group A, a statistically significant worsening of motor and sensory
      conductance in the upper and lower limbs was observed; in group B, a
      statistically significant improvement was found. These findings suggest that
      hemofiltration has a more beneficial effect on motor and sensory conductivity
      than does conventional hemodialysis.

PMID- 28452449
TI  - Daily Dialysis: Toward a New Standard in Well-Being.
AB  - Daily hemodialysis (DHD) is a promising option; however, logistic obstacles and
      clinical perplexities limit its dissemination. Understanding the mechanisms of,
      and the time until, the onset of improved well-being may help to quantify
      clinical advantages and to define the minimum length of a "trial" of daily
      dialysis. By following 30 patients treated in 4 centers, this study aimed to
      determine how long a period of time is needed until a patient experiences
      subjective improvement. From November 1998 to November 2000, 30 patients tried at
      least 2 weeks of short daily dialysis in four Northern Italian centers of
      Piemonte and Valle d'Aosta. The DHD (2 - 3 hours; blood flow 270 - 350 mL/min;
      individual HCO3 , Na, K) was performed at home or in a center. Motivations to try
      DHD, fears and concerns regarding DHD, and changes in perceived well-being were
      assessed by semi-structured interview. The main clinical indications for a trial
      of DHD were poor tolerance of conventional treatment, cardiovascular disease, and
      hypertension or hypotension; only 6 patients had no comorbidity at start. The
      patients' main reasons for choosing DHD were related to job problems and the
      search for a better treatment. Most of the patients continued DHD because of
      improved well-being; logistic reasons accounted for the drop-outs (5 patients).
      The main fears were related to logistic aspects, vascular access problems, and
      excessive involvement of the partner on home dialysis. Improved well-being was
      reported by 28 of 30 patients; 2 patients reported no difference. Subjective
      improvement was perceived within 2 weeks in 22 of 30 patients, and within 1 month
      in 28 of 30 patients. An offer of a 2 - 4 week trial of DHD may help patients and
      caregivers to determine whether subjective and objective benefits outweigh
      logistic problems and whether a permanent transfer to DHD is worthwhile.

PMID- 28452450
TI  - Lipid Metabolism and Cardiovascular Morbidity and Mortality in Hemodialysis
      Patients: Role of Factors Modulating Cytosolic Calcium.
AB  - Animal studies indicate that insulin resistance and glucose intolerance leading
      to dyslipidemia in uremic rats are associated with increased cytosolic calcium
      ([Ca++ i]). The resistance and intolerance are reversed with verapamil, but recur
      after its discontinuation. This finding suggests that hyperparathyroid-induced
      [Ca ++ i] increase is responsible for the metabolic derangement. We
      retrospectively examined, over a 12-year period, the effects of factors that
      lower [Ca ++ i] on total serum cholesterol and triglycerides in 332 hemodialysis
      (HD) patients. Because the study was retrospective, detailed lipid profiles were
      not available. We therefore relied on morbidity and mortality outcomes related to
      atherosclerotic vascular disease. Patients with diabetes mellitus were excluded,
      because their dyslipidemia and vascular disease are mediated via a different
      mechanism. Four groups emerged: group I [high parathormone (PTH) in the absence
      of calcium channel blockers (CCBs), n = 107], representing the highest [Ca++ i];
      group II (high PTH in the presence of CCBs, n = 76) and group III (lower PTH in
      the absence of CCBs, n = 66), representing intermediate [Ca ++ i]; and group IV
      (lower PTH in the presence of CCBs, n = 83) representing the lowest [Ca ++ i].
      The theoretically lower [Ca ++ i] was achieved via CCB therapy or lower PTH, or
      both. The mean serum cholesterol in group I was 322 +/- 24 mg/dL and the level of
      triglycerides was 398 +/- 34 mg/dL. Group II had mean serum cholesterol of 196 +/
      16 mg/dL and triglycerides of 157 +/- 17 mg/dL. Group III had a mean serum
      cholesterol of 202 +/- 19 mg/dL and triglycerides of 160 +/- 15 mg/dL. Group IV
      had a mean serum cholesterol of 183 +/- 9 mg/dL and triglycerides of 94 +/- 6
      mg/dL. The differences in cholesterol and triglyceride levels among four groups
      were significant (p < 0.001) by one-way analysis of variance (ANOVA). The
      incidence of cardiovascular morbidity and mortality events was 61% in group I,
      24% in group II, 28% in group III, and 18% in group IV (chi 2 = 47.7, p < 0.001).
      We conclude that, in non diabetic HD patients, hyperparathyroidism, especially in
      the absence of CCBs, is associated with severe dyslipidemia and increased risk of
      cardiovascular morbidity and mortality. Dyslipidemia may be related to a
      hyperparathyroid-induced increase in cytosolic calcium [Ca++ i]. Lowering [Ca++
      i] by decreasing PTH or by blocking calcium entry into cells (via CCBs), or both,
      is associated with less dyslipidemia and improved long-term cardiovascular
      morbidity and mortality. Prospective randomized studies, with actual measurement
      of [Ca ++ i], are needed to verify the results of this study.

PMID- 28452451
TI  - The impact of nerve-sparing robot-assisted radical prostatectomy on lower urinary
      tract function: Prospective assessment of patient-reported outcomes and frequency
      volume charts.
AB  - AIMS: To elucidate the effects of a nerve-sparing (NS) procedure on lower urinary
      tract symptoms (LUTS) and urinary function after robot-assisted radical
      prostatectomy (RARP), the associations between the NS procedure and LUTS and
      urinary function were investigated. METHODS: The participants in this study were
      200 consecutive patients who underwent RARP. These patients were categorized into
      unilateral and bilateral NS groups and the non-NS group. The International
      Prostate Symptom Score (IPSS), quality of life (QOL) index, frequency-volume
      chart, uroflowmetry, 1-h pad test, and the 5-item International Index of Erectile
      Function (IIEF-5) questionnaire were evaluated before and after RARP. RESULTS:
      The total IPSS score was significantly lower in the unilateral (P = 0.03) and
      bilateral NS groups (P = 0.03) than in the non-NS group after RARP. Diurnal
      maximum voided volume (MVV) values were significantly greater in the bilateral NS
      group than in the non-NS group after RARP (P = 0.002). Nocturnal frequency was
      significantly decreased in the unilateral NS group than in the non-NS group after
      RARP (3 months P = 0.01, 12 months P = 0.01). Erectile function was significantly
      better in both the unilateral NS group (P < 0.0001) and the bilateral NS group (P
      = 0.02) than in the non-NS group 12 months after RARP. CONCLUSIONS: The NS
      procedure in RARP has the possibility to improve not only erectile function, but
      also LUTS, owing to both the increase of MVV and the decrease of nocturia.
      Therefore, the NS procedure is also recommended from the viewpoint of early
      improvement of LUTS and lower urinary tract dysfunction after RARP.

PMID- 28452452
TI  - Weight loss in videoconference and in-person iDiet weight loss programs in
      worksites and community groups.
AB  - OBJECTIVE: To examine the association of program delivery factors with weight
      loss (WL) in enrollees in iDiet(r) , a commercial WL program. METHODS: Data were
      from 644 adults enrolling in an 11-week group WL program and 461 who reported
      weight to 11 weeks (complete reporters). Predictors of %WL were analyzed using
      ANCOVA, including meeting type (in-person vs. videoconference), participant type
      (worksite employees vs. community members), age, gender, BMI, and payment
      structure. RESULTS: Mean starting BMI was 32.4 +/- 7.1 (mean +/- SD); WL was 6.1
      +/- 3.9% in all enrollees in an intention-to-treat analysis and 7.4 +/- 3.4% in
      complete reporters. Videoconference participants, older adults, and enrollees in
      incentivized programs were more likely to be complete reporters (P < 0.004). %WL
      at 11 weeks was not associated with gender, starting BMI, or videoconference
      versus in-person groups. Worksite participants had greater %WL than community
      participants (+1.2%, P < 0.001), and there was no significant difference in %WL
      between programs paid by the employee or employer. Greater %WL was achieved by
      individuals >=30 versus < 30 years (+2.2%, P < 0.001) and by those enrolling in
      January-March versus April-June (+1.4%, P = 0.02). CONCLUSIONS: iDiet
      participants had clinically impactful mean WL. The observed high mean WL in
      worksites and videoconference-delivered programs broadens options for scalable WL
      program implementation.

PMID- 28452453
TI  - ERRATUM: NEXT-GENERATION ANALYSIS OF CATARACTS: DETERMINING KNOWLEDGE DRIVEN GENE
      GENE INTERACTIONS USING BIOFILTER, AND GENE-ENVIRONMENT INTERACTIONS USING THE
      PHENX TOOLKIT.
AB  - This corrects the above-titled article. There was an error in the case-control
      label for a subset of samples. This was corrected and analyses were re-run. The
      thrust of the results and discussion did not change, but these results are more
      precise and corrected.

PMID- 28452455
TI  - Hierarchical NiCo2O4 Micro- and Nanostructures with Tunable Morphologies as Anode
      Materials for Lithium- and Sodium-Ion Batteries.
AB  - NiCo2O4 microrods with open structures are successfully synthesized using a
      solvothermal method. Compared with those of dense microspheres, the one
      dimensional (1D) porous microrods show much higher capacities and stability for
      both Li- and Na-ion batteries due to the 1D open structure facilitating fast ion
      transport and buffering volumetric change during charge/discharge. This work
      demonstrates that the electrochemical performance of NiCo2O4 is highly dependent
      on morphologies of the active material.

PMID- 28452454
TI  - Real-Time in Vivo Detection of H2O2 Using Hyperpolarized 13C-Thiourea.
AB  - Reactive oxygen species (ROS) are essential cellular metabolites widely
      implicated in many diseases including cancer, inflammation, and cardiovascular
      and neurodegenerative disorders. Yet, ROS signaling remains poorly understood,
      and their measurements are a challenge due to high reactivity and instability.
      Here, we report the development of 13C-thiourea as a probe to detect and measure
      H2O2 dynamics with high sensitivity and spatiotemporal resolution using
      hyperpolarized 13C magnetic resonance spectroscopic imaging. In particular, we
      show 13C-thiourea to be highly polarizable and to possess a long spin-lattice
      relaxation time (T1), which enables real-time monitoring of ROS-mediated
      transformation. We also demonstrate that 13C-thiourea reacts readily with H2O2 to
      give chemically distinguishable products in vitro and validate their detection in
      vivo in a mouse liver. This study suggests that 13C-thiourea is a promising agent
      for noninvasive detection of H2O2 in vivo. More broadly, our findings outline a
      viable clinical application for H2O2 detection in patients with a range of
      diseases.

PMID- 28452456
TI  - Polylactic Acid Sealed Polyelectrolyte Multilayer Microchambers for Entrapment of
      Salts and Small Hydrophilic Molecules Precipitates.
AB  - Efficient depot systems for entrapment and storage of small water-soluble
      molecules are of high demand for wide variety of applications ranging from
      implant based drug delivery in medicine and catalysis in chemical processes to
      anticorrosive systems in industry where surface-mediated active component
      delivery is required on a time and site specific manner. This work reports the
      fabrication of individually sealed hollow-structured polyelectrolyte multilayer
      (PEM) microchamber arrays based on layer-by-layer self-assembly as scaffolds and
      microcontact printing. These PEM chambers are composed out of biocompatible
      polyelectrolytes and sealed by a monolayer of hydrophobic biocompatible and
      biodegradable polylactic acid (PLA). Coating the chambers with hydrophobic PLA
      allows for entrapment of a microair-bubble in each chamber that seals and hence
      drastically reduces the PEM permeability. PLA@PEM microchambers are proven to
      enable prolonged subaqueous storage of small hydrophilic salts and molecules such
      as crystalline NaCl, doxicycline, and fluorescent dye rhodamine B. The presented
      microchambers are able to entrap air bubbles and demonstrate a novel strategy for
      entrapment, storage, and protection of micropackaged water-soluble substances in
      precipitated form. These chambers allow triggered release as demonstrated by
      ultrasound responsiveness of the chambers. Low-frequency ultrasound exposure is
      utilized for microchamber opening and payload release.

PMID- 28452457
TI  - Tunable Upper Critical Solution Temperature of Poly(N-isopropylacrylamide) in
      Ionic Liquids for Sequential and Reversible Self-Folding.
AB  - We demonstrate sequential folding of micropatterned polymer actuators by tuning
      the upper critical solution temperature (UCST) of poly(N-isopropylacrylamide)
      (PNIPAM) copolymers in the ionic liquid (IL) 1-ethyl-3-methylimidazolium
      bis(trifluoro-methylsulfonyl) imide. Incorporation of comonomers having different
      hydrogen-bonding capacities, acrylic acid and methyl acrylate, is shown to shift
      the UCST of PNIPAM to higher and lower temperatures, respectively. Relying on the
      ability to tune the transition temperature through copolymerization along with
      the wide thermal range afforded by the IL as a solvent, we fabricated a
      photopatterned self-folding device which shows reversible and sequential bending
      of three sets of hinges. Such sequential and reversible bending of microactuators
      offers potential for the design of complex self-folding origami and soft robots.

PMID- 28452458
TI  - Chiro-Optical Modulation for NURR1 Production from Stem Cells.
AB  - Nuclear receptor related 1 (NURR1) is an essential protein for maintenance of
      dopaminergic neurons in adult midbrain of which deficiency leads to Parkinson's
      disease. To enhance the NURR1 production of neural cells, various approaches are
      under investigation. Here we report that NURR1 is highly expressed in stem cells
      by exposure to an L-polarized blue light emitting diode (LED). Compared to stem
      cells cultured in the absence of a LED, under polarized green and red LEDs, the
      stem cells exposed to a polarized blue LED significantly enhanced neuronal
      biomarkers such as neurofilament M (NFM) and neuron specific enolase (NSE) at
      both mRNA and protein levels. In particular, NURR1 was selectively enhanced by
      the stem cells exposed to the L-polarized blue LED. Stem cells exposed to the L
      polarized blue LED increased mitochondrial ATP and intracellular calcium ions,
      which support neuronal differentiation of the stem cells. This study suggests
      that chiro-optical treatments by using polarized light with a specific wavelength
      can be used for engineering of stem cells with enhanced specific biochemicals,
      which may open a new method for a specific disease.

PMID- 28452459
TI  - Simple, Large-Scale Fabrication of Uniform Raman-Enhancing Substrate with
      Enhancement Saturation.
AB  - It is well-known that gold nanoparticle (AuNP) clusters generate strong surface
      enhanced Raman scattering (SERS). In order to produce spatially uniform Raman
      enhancing substrates at a large scale, we synthesized vertically perforated three
      dimensional (3D) AuNP stacks. The 3D stacks were fabricated by first
      hydrothermally synthesizing ZnO nanowires perpendicular to silicon wafers
      followed by repetitively performing liquid-phase deposition of AuNPs on the tops
      and side surfaces of the nanowires. During the deposition process, the nanowires
      were shown to gradually dissolve away, leaving hollow vestiges or perforations
      surrounded by stacks of AuNPs. Simulation studies and experimental measurements
      reveal these nanoscale perforations serve as light paths that allow the
      excitation light to excite deeper regions of the 3D stacks for stronger overall
      Raman emission. Combined with properly sized nanoparticles, this feature
      maximizes and saturates the Raman enhancement at 1-pM sensitivity across the
      entire wafer-scale substrate, and the saturation improves the wafer-scale
      uniformity by a factor of 6 when compared to nanoparticle layers deposited
      directly on a silicon wafer substrate. Using the 3D-stacked substrates,
      quantitative sensing of adenine molecules yielded concentrations measurements
      within 10% of the known value. Understanding the enhancing mechanisms and
      engineering the 3D stacks have opened a new method of harnessing the intense SERS
      observed in nanoparticle clusters and realize practical SERS substrates with
      significantly improved uniformity suitable for quantitative chemical sensing.

PMID- 28452460
TI  - Synthetic Melanin E-Ink.
AB  - Extensive efforts have been devoted to the development of surfactant-free
      electronic ink (E-ink) with excellent display resolution for high-definition
      resolution display. Herein, we report the use of polydopamine-based synthetic
      melanin, a class of functional nanoparticles with similar chemical compositions
      and physical properties to those of naturally occurring melanin, as a new E-ink
      material. It was found that such E-ink displays could achieve ultrahigh
      resolution (>10 000 ppi) and low power consumption (operation voltage of only 1
      V) in aqueous solutions. Interestingly, simple oxidation of synthetic melanin
      nanoparticles enables the generation of intrinsic fluorescence, allowing further
      development of fluorescent E-ink displays with nanoscale resolution. We describe
      these bioinspired materials in an initial proof-of-concept study and propose that
      synthetic melanin nanoparticles will be suitable for electronic nanoinks with a
      potential wide range of applications in molecular patterning and fluorescence
      bioimaging.

PMID- 28452461
TI  - Fabrication of a Microlens Array with Controlled Curvature by Thermally Curving
      Photosensitive Gel Film beneath Microholes.
AB  - A rapid method is developed for fabricating low-cost and high-numerical-aperture
      photosensitive-gel microlens arrays (MLAs) with well-controlled curvatures. An UV
      curable photosensitive-gel film beneath the microholes of a silicon mold can be
      flexibly deformed by thermally manipulating the surface tension of the
      photosensitive gel and the pressure difference across the air-photosensitive-gel
      interface. The concave interface is then solidified through UV curing, forming a
      MLA with a concave curvature. MLAs with a focal length ranging from 51.4 to 71.9
      MUm and a numerical aperture (NA) of 0.49 were fabricated. The photocured MLA has
      high mechanical and thermal strength and is suitable as a master mold for the
      further production of convex MLAs. The fabricated microlenses have uniform shapes
      and smooth surfaces. In a demonstration of imaging and focusing performance,
      clear and uniform images and focused light spots were observed using concave and
      convex MLAs.

PMID- 28452463
TI  - Inverse Magnetoresistance in Polymer Spin Valves.
AB  - In this work, both negative and positive magnetoresistance (MR) in solution
      processed regioregular poly(3-hexylthiophene) (RR-P3HT) is observed in organic
      spin valves (OSVs) with vertical La2/3Sr1/3MnO3 (LSMO)/P3HT/AlOx/Co
      configuration. The ferromagnetic (FM) LSMO electrode with near-atomic flatness is
      fabricated by a DC facing-target magnetron sputtering method. This research is
      focused on the origin of the MR inversion. Two types of devices are investigated
      in details: One with Co penetration shows a negative MR of 0.2%, while the other
      well-defined device with a nonlinear behavior has a positive MR of 15.6%. The MR
      measurements in LSMO/AlOx/Co and LSMO/Co junctions are carried to exclude the
      interference of insulating layer and two FM electrodes themselves. By examining
      the Co thicknesses and their corresponding magnetic hysteresis loops, a spin
      dependent hybrid-interface-state model by Co penetration is induced to explain
      the MR sign inversion. These results proven by density functional theory (DFT)
      calculations may shed light on the controllable interfacial properties in
      designing novel OSV devices.

PMID- 28452462
TI  - Glycan Remodeling of Human Erythropoietin (EPO) Through Combined Mammalian Cell
      Engineering and Chemoenzymatic Transglycosylation.
AB  - The tremendous structural heterogeneity of N-glycosylation of glycoproteins poses
      a great challenge for deciphering the biological functions of specific glycoforms
      and for developing protein-based therapeutics. We have previously reported a
      chemoenzymatic glycan remodeling method for producing homogeneous glycoforms of N
      glycoproteins including intact antibodies, which consist of endoglycosidase
      catalyzed deglycosylation and novel glycosynthase-catalyzed transglycosylation,
      but its application to complex glycoproteins carrying multiple N-glycans remains
      to be examined. We report here site-selective chemoenzymatic glycosylation
      remodeling of recombinant human erythropoietin (EPO) that contains three N
      glycans. We found that the generation of a HEK293S GnT I knockout FUT8
      overexpressing cell line enabled the production of an unusual Man5GlcNAc2Fuc
      glycoform, which could be converted to the core-fucosylated GlcNAc-EPO
      intermediate acceptor for enzymatic transglycosylation. With this acceptor,
      homogeneous sialylated glycoform or azide-tagged glycoform were produced using
      the glycosynthase (EndoF3-D165A) catalyzed transglycosylation. Interestingly, a
      remarkable site-selectivity was observed in the transglycosylation reactions,
      leading to the introduction of two N-glycans selectively at the Asn-38 and Asn-83
      sites, which was confirmed by a detailed MS/MS analysis of the transglycosylation
      product. Finally, a different N-glycan was attached at the third (Asn-24) site by
      pushing the enzymatic transglycosylation with a distinct glycan oxazoline,
      achieving the site-selective glycosylation modification of the protein. This
      study represents the first example of site-selective chemoenzymatic glycan
      engineering of complex glycoproteins carrying multiple N-glycans.

PMID- 28452464
TI  - Nanoscale Characterization of Back Surfaces and Interfaces in Thin-Film Kesterite
      Solar Cells.
AB  - Combinations of sub 1 MUm absorber films with high-work-function back surface
      contact layers are expected to induce large enough internal fields to overcome
      adverse effects of bulk defects on thin-film photovoltaic performance,
      particularly in earth-abundant kesterites. However, there are numerous
      experimental challenges involving back surface engineering, which includes
      exfoliation, thinning, and contact layer optimization. In the present study, a
      unique combination of nanocharacterization tools, including nano-Auger, Kelvin
      probe force microscopy (KPFM), and cryogenic focused ion beam measurements, are
      employed to gauge the possibility of surface potential modification in the
      absorber back surface via direct deposition of high-work-function metal oxides on
      exfoliated surfaces. Nano-Auger measurements showed large compositional
      nonuniformities on the exfoliated surfaces, which can be minimized by a brief
      bromine-methanol etching step. Cross-sectional nano-Auger and KPFM measurements
      on Au/MoO3/Cu2ZnSn(S,Se)4 (CZTSSe) showed an upward band bending as large as 400
      meV within the CZTSSe layer, consistent with the high work function of MoO3,
      despite Au incorporation into the oxide layer. Density functional theory
      simulations of the atomic structure for bulk amorphous MoO3 demonstrated the
      presence of large voids within MoO3 enabling Au in-diffusion. With a less
      diffusive metal electrode such as Pt or Pd, upward band bending beyond this level
      is expected to be achieved.

PMID- 28452465
TI  - Highly Efficient Fumed Silica Nanoparticles for Peptide Bond Formation:
      Converting Alanine to Alanine Anhydride.
AB  - In this work, thermal condensation of alanine adsorbed on fumed silica
      nanoparticles is investigated using thermal analysis and multiple spectroscopic
      techniques, including infrared (IR), Raman, and nuclear magnetic resonance (NMR)
      spectroscopies. Thermal analysis shows that adsorbed alanine can undergo thermal
      condensation, forming peptide bonds within a short time period and at a lower
      temperature (~170  degrees C) on fumed silica nanoparticle surfaces than that in
      bulk (~210  degrees C). Spectroscopic results further show that alanine is
      converted to alanine anhydride with a yield of 98.8% during thermal condensation.
      After comparing peptide formation on solution-derived colloidal silica
      nanoparticles, it is found that fumed silica nanoparticles show much better
      efficiency and selectivity than solution-derived colloidal silica nanoparticles
      for synthesizing alanine anhydride. Furthermore, Raman spectroscopy provides
      evidence that the high efficiency for fumed silica nanoparticles is likely
      related to their unique surface features: the intrinsic high population of
      strained ring structures present at the surface. This work indicates the great
      potential of fumed silica nanoparticles in synthesizing peptides with high
      efficiency and selectivity.

PMID- 28452466
TI  - Three-Dimensional Continuous Conductive Nanostructure for Highly Sensitive and
      Stretchable Strain Sensor.
AB  - The demand for wearable strain gauges that can detect dynamic human motions is
      growing in the area of healthcare technology. However, the realization of
      efficient sensing materials for effective detection of human motions in daily
      life is technically challenging due to the absence of the optimally designed
      electrode. Here, we propose a novel concept for overcoming the intrinsic limits
      of conventional strain sensors based on planar electrodes by developing highly
      periodic and three-dimensional (3D) bicontinuous nanoporous electrodes. We create
      a 3D bicontinuous nanoporous electrode by constructing conductive percolation
      networks along the surface of porous 3D nanostructured poly(dimethylsiloxane)
      with single-walled carbon nanotubes. The 3D structural platform allows
      fabrication of a strain sensor with robust properties such as a gauge factor of
      up to 134 at a tensile strain of 40%, a widened detection range of up to 160%,
      and a cyclic property of over 1000 cycles. Collectively, this study provides new
      design opportunities for a highly efficient sensing system that finely captures
      human motions, including phonations and joint movements.

PMID- 28452467
TI  - Biosynthetic Insights into Linaridin Natural Products from Genome Mining and
      Precursor Peptide Mutagenesis.
AB  - Linaridin is a small class of peptide natural products belonging to the
      ribosomally synthesized and post-translationally modified peptides (RiPPs)
      superfamily. By an extensive genome-wide survey of linaridin biosynthetic genes,
      we show that this class of natural products is widespread in nature and possesses
      vast structural diversity. The linaridin precursor peptides are relatively
      conserved in the N-termini but have diverse sequences in the core region, which
      appear to have coevolved with the biosynthetic enzymes. Using the prototypic
      linaridin cypemycin as a model, we have explored the structure-activity
      relationships involved in precursor peptide maturation and generated a diverse
      set of novel cypemycin variants, among which the T2S variant exhibits enhanced
      activity against Micrococcus luteus. Our results reveal valuable insights into
      linaridin biosynthesis and highlight the potential to explore this class of
      natural products by genome mining and by biosynthetic engineering studies.

PMID- 28452468
TI  - Directing Assembly and Disassembly of 2D MoS2 Nanosheets with DNA for Drug
      Delivery.
AB  - Layer-by-layer (LbL) self-assembled stacked Testudo-like MoS2 superstructures
      carrying cancer drugs are formed from nanosheets controllably assembled with
      sequence-based DNA oligonucleotides. These superstructures can disassemble
      autonomously in response to cancer cells' heightened ATP metabolism. First, we
      functionalize MoS2 nanosheets (MoS2-NS) nanostructures with DNA oligonucleotides
      having thiol-terminated groups (DNA/MoS2-NS) via strong binding to sulfur atom
      defect vacancies on MoS2 surfaces. The driving force to assemble into a higher
      order DNA/MoS2-NS superstructure is guided by a linker aptamer that induced
      interlayer assembly. In the presence of target ATP molecules, these multilayer
      superstructures disassembled as a consequence of stronger binding of ATP
      molecules with the linking aptamers. This design plays a dual role of protection
      and delivery by LbL stacked MoS2-NS similar in concept to a Greek Testudo. These
      superstructures present a protective armor-like shell of MoS2-NS, which still
      remains responsive to small and infiltrating ATP molecules diffusing through the
      protective MoS2-NS, contributing to an enhanced stimuli-responsive drug release
      system for targeted chemotherapy.

PMID- 28452469
TI  - General Strategy for the Synthesis of Transition-Metal Phosphide/N-Doped Carbon
      Frameworks for Hydrogen and Oxygen Evolution.
AB  - Transition metal phosphides (TMPs) have been identified as promising nonprecious
      metal electrocatalyst for hydrogen evolution reaction (HER) and other energy
      conversion reactions. Herein, we reported a general strategy for synthesis of a
      series of TMPs (Fe2P, FeP, Co2P, CoP, Ni2P, and Ni12P5) nanoparticles (NPs) with
      different metal phases embedded in a N-doped carbon (NC) matrix using metal salt,
      ammonium dihydrogen phosphate, and melamine as precursor with varying molar
      ratios and thermolysis temperatures. The resultant TMPs can serve as highly
      active and durable bifunctional electrocatalyst toward HER and oxygen evolution
      reaction (OER). In particular, the Ni2P@NC phase only requires an overpotential
      of ~138 mV to derive HER in 0.5 M H2SO4, and ~320 mV for OER in 1.0 M KOH at the
      current density of 10 mA cm-2. Because of the encapsulation of NC that can
      effectively prevent corrosion of embedded TMP NPs, Ni2P@NC exhibits almost
      unfading catalytic performance even after 10 h under both acidic and alkaline
      solutions. This synthesis strategy provides a new avenue to exploring TMPs as
      highly active and stable electrocatalyst for the HER, OER, and other
      electrochemical applications.

PMID- 28452470
TI  - Correction to Carbyne from First-Principles: Chain of C Atoms, a Nanorod or a
      Nanorope.

PMID- 28452471
TI  - Increasing the Sensitivity to Short-Lived Species in a Modulated Excitation
      Experiment.
AB  - The combination of spectroscopic and diffraction methods to study chemical
      transformations is fundamental for the understanding of reaction mechanisms. The
      identification of short-lived species, likely active species, is often hindered
      by the contribution of spectator species not directly involved in the reaction.
      The present study considers two different approaches to obtain increased
      sensitivity to transient species for experiments obeying the modulated excitation
      paradigm and exploiting phase sensitive detection (PSD). First, the variation of
      the frequency of the external stimulation (omega) during the experiment is
      considered. We demonstrate using the Fourier analysis that the increase of omega,
      i.e., the decrease of the modulation period T, enhances the sensitivity to short
      lived species. The second alternative is the use of a single stimulation
      frequency (omega) during the measurement and the variation of the demodulation
      frequency (nomega) during data analysis. The absolute intensity of the phase
      resolved signals is reduced by increasing n. However, species with slow kinetics
      are more attenuated than species with fast kinetics. Thus, transient species
      possessing fast kinetics are enhanced relative to other components and can be, in
      principle, discerned with improved sensitivity in the phase-resolved data
      obtained with n > 1. Experimental results in the field of heterogeneous catalysis
      are provided that support our findings.

PMID- 28452472
TI  - An Uncanny Dehydrogenation Mechanism: Polar Bond Control over Stepwise or
      Concerted Transition States.
AB  - The mechanism of the dehydrogenation of N-heterocycles with the recently
      established bifunctional catalyst (iPrPNP)Fe(CO)(H) was investigated through
      experiments and density functional theory calculations (iPrPNP =
      iPr2PCH2CH2NCH2CH2PiPr2). In this system, the saturated N-heterocyclic substrates
      are completely dehydrogenated to the aromatic products. Calculations indicate
      that dehydrogenation barriers of the C-C bonds are very high in energy (DeltaG? =
      37.4-42.2 kcal/mol), and thus dehydrogenation only occurs at the C-N bond
      (DeltaG? = 9.6-22.2 kcal/mol). Interestingly, substrates like piperidine with
      relatively unpolarized C-N bonds are dehydrogenated through a concerted
      proton/hydride transfer bifunctional transition state involving the nitrogen on
      the PNP ligand. However, substrates with polarized C-N bonds entail stepwise
      (proton then hydride) bifunctional dehydrogenation.

PMID- 28452473
TI  - Enzyme Shielding in a Large Mesoporous Hollow Silica Shell for Improved Recycling
      and Stability Based on CaCO3 Microtemplates and Biomimetic Silicification.
AB  - We report a novel "anchor-shield" approach for synthesizing a yolk-shell
      structured biocatalytic system that consists of a phenylalanine ammonia lyase
      (PAL) protein particle core and a hollow silica shell with large mesopores by a
      combination of CaCO3 microtemplates and biomimetic silicification. The method is
      established upon filling porous CaCO3 cores with PAL via co-precipitation,
      controlled self-assembly and polycondensation of silanes, cross-link of the PAL
      molecules, and subsequent CaCO3 dissolution. During this process, the self
      assembled layer of cetyltrimethylammonium bromide served as a structure-directing
      agent of the mesostructure and directed the overgrowth of the mesostructured
      silica on the external surface of PAL/CaCO3 hybrid microspheres; after CaCO3
      dissolution, the cross-linked PAL particles were encapsulated in the hollow
      silica shell. The hollow silica shell around the enzyme particles provided a
      "shield" to protect from biological, thermal, and chemical degradation for the
      enzyme. As a result, the recycling of the PAL enzyme was improved remarkably in
      comparison to adsorbed PAL on CaCO3. PAL particles with a hollow silica shell
      still retained 60% of their original activity after 13 cycles, whereas adsorbed
      PAL on CaCO3 microparticles lost activity after 7 cycles. Moreover, immobilized
      PAL exhibited higher stability against a proteolytic agent, denaturants, heat,
      and extreme pH than adsorbed PAL on CaCO3 microparticles. These results
      demonstrated that the "anchor-shield" approach is an efficient method to obtain a
      stable and recycled biocatalyst with a yolk-shell structure.

PMID- 28452474
TI  - Steady-State Kinetics of alpha-Synuclein Ferrireductase Activity Identifies the
      Catalytically Competent Species.
AB  - alpha-Synuclein (alpha-syn) is a cytosolic protein known for its association with
      neurodegenerative diseases, including Parkinson's disease and other
      synucleinopathies. The potential cellular function of alpha-synuclein may be of
      consequence for understanding the pathogenesis of such diseases. Previous work
      has suggested that alpha-synuclein can catalyze the reduction of iron as a
      ferrireductase. We performed a detailed analysis of the steady-state kinetics of
      recombinant alpha-syn ferrireductase activity and for disease-associated
      variants. Our study illustrates that the ferrireductase activity we observed is
      clearly commensurate with bona fide enzyme activity and suggests a mechanistic
      rationale for the activity and the relationship to cellular regulation of the
      pool of Fe(III) and Fe(II). Using cell-based studies, we examined the
      functionally active conformation and found that the major catalytically active
      form is a putative membrane-associated tetramer. Using an artificial membrane
      environment with recombinant protein, we demonstrate that secondary structure
      folding of alpha-synuclein is insufficient to allow enzyme activity and the
      absolute specificity of the tertiary/quaternary structure is the primary
      requirement. Finally, we explored the steady-state kinetics of a range of disease
      alpha-synuclein variants and found that variants involved in neurodegenerative
      disease exhibited major changes in their enzymatic activity. We discuss these
      data in the context of a potential disease-associated mechanism for aberrant
      alpha-synuclein ferrireductase activity.

PMID- 28452475
TI  - Hydrolysis in Acidic Environment and Degradation of Satraplatin: A Joint
      Experimental and Theoretical Investigation.
AB  - For the synthesis and selection of active platinum-based anticancer drugs that
      perform better than cisplatin and its analogues, six-coordinate octahedral Pt(IV)
      complexes appear to be promising candidates as, being kinetically more inert and
      more resistant to ligand substitution than four-coordinate Pt(II) centers, they
      are able to minimize unwanted side reactions with biomolecules prior to DNA
      binding. Due to their kinetic inertness, Pt(IV) complexes have also been
      exploited to bypass inconvenient intravenous administration. The most prominent
      example is satraplatin (Sat.) which is the first platinum antineoplastic agent
      reported to have oral activity. The present paper deals with a theoretical DFT
      investigation of the influence that the acidity of the biological environment can
      have on the activity of satraplatin and analogous octahedral Pt(IV) complexes
      having two carboxylates as axial ligands. Moreover, here the outcomes of a joint
      electrospray ionization mass spectrometry and DFT investigation of the
      fragmentation pathways of the protonated satraplatin are reported. Calculations
      show that the simulated acidic environment has an important impact on the
      satraplatin reactivity causing a significant lowering of the barrier that is
      necessary to overcome for the hydrolysis of the first acetate ligand to occur.
      Data from electrospray ionization mass spectrometry, 1H NMR, and potentiometric
      experiments strongly suggest that the loss of CH3COOH from the protonated
      satraplatin ion [Sat. + H]+ takes place almost immediately upon dissolution of
      satraplatin in methanol-water, D2O, and water solutions, respectively, at room
      temperature.

PMID- 28452476
TI  - Impact of Processing on the Protein Quality of Pinto Bean (Phaseolus vulgaris)
      and Buckwheat (Fagopyrum esculentum Moench) Flours and Blends, As Determined by
      in Vitro and in Vivo Methodologies.
AB  - Blending of protein sources can increase protein quality by compensating for
      limiting amino acids present in individual sources, whereas processing grain
      flours by extrusion or baking can also alter protein quality. To determine the
      effect of baking and extrusion on the protein quality of blended flours from
      buckwheat and pinto beans, a rodent bioassay was performed and compared to an in
      vitro method of protein quality determination. Overall, extruded products had
      higher protein efficiency ratio values, increased digestibility, and greater
      protein digestibility corrected amino acid score (PDCAAS) values than baked
      products, with the extruded buckwheat/pinto blend having the greatest PDCAAS
      value of the experimental diets investigated. A correlation was found between
      both digestibility and PDCAAS values generated from in vitro and in vivo methods.
      The use of in vitro digestibility analysis should be investigated as a potential
      replacement for the current rodent assay for nutrient content claim purposes.

PMID- 28452477
TI  - Manzamine Alkaloids from an Acanthostrongylophora sp. Sponge.
AB  - Five new manzamine alkaloids (1-5) and new salt forms of two known manzamines (6
      and 7), along with seven known compounds (8-14) of the same structural class,
      were isolated from an Indonesian Acanthostrongylophora sp. sponge. On the basis
      of the results of combined spectroscopic analyses, the structure of kepulauamine
      A (1) was determined to possess an unprecedented pyrrolizine moiety, while others
      were functional group variants of known manzamines. These compounds exhibited
      weak cytotoxicity, moderate antibacterial activity, and mild inhibition against
      the enzyme isocitrate lyase.

PMID- 28452478
TI  - Solid State Separation and Isolation of Tautomers of Fused-Ring
      Triazolotriazoles.
AB  - Fine control of the tautomeric forms of [1,2,4]triazolo[3,2-c][1,2,4]triazole
      derivatives in acidic conditions has been achieved by acting on the electronic
      character of the substituent at position 7 of the heterobicycle and on the
      counterion. Strong electron releasing or electron withdrawing substituents lead
      almost exclusively to a single tautomeric form, the 1H-3H or the 2H-3H,
      respectively. In the case of the phenol substituent, both tautomeric forms are
      present in comparable amount in solution; the two tautomers can also be
      selectively precipitated in different crystalline salts using suitable
      counterions.

PMID- 28452479
TI  - A "Brick Mass Spectrometer" Driven by a Sinusoidal Frequency Scanning Technique.
AB  - In this work, a "brick" size miniature mass spectrometer (28 cm * 21 cm * 16 cm)
      was developed and characterized, which was enabled by the development of a new
      frequency scanning technique. Different from the conventional voltage scanning
      method or the digital waveforms used on a digital ion trap, a sinusoidal
      frequency scanning technique was developed to drive the linear ion trap of the
      brick mass spectrometer (BMS). Both an in-vacuum plasma ionization source and an
      electrospray ionization source were coupled with this BMS for the analyses of
      volatile and nonvolatile samples. Stability diagram, sensitivity, mass
      resolution, and mass range of the BMS were explored. This new frequency scanning
      technique could not only reduce the size and power consumption of a miniature
      mass spectrometer but also improve its analytical performances, especially in
      terms of mass range and resolution. Analogous to the development of cell phones,
      this BMS would be an important step from "brick" mass spectrometer to "cell" mass
      spectrometer.

PMID- 28452480
TI  - Rutile TiO2 Flocculent Ripples with High Antireflectivity and Superhydrophobicity
      on the Surface of Titanium under 10 ns Laser Irradiation without Focusing.
AB  - We report on the formation of rutile TiO2 flocculent laser-induced periodic
      surface structures (LIPSSs) with high antireflectivity and superhydrophobicity on
      the surface of titanium under 10 ns 1064 nm laser irradiation without focusing.
      The center part of the Gaussian laser beam is used to deposit flocculent
      structure and the edge part used to produce LIPSSs. The melt and modification
      thresholds of titanium were determined first, and then, the melt and modification
      spot-overlap numbers, several responsible for the formation of flocculent
      structure and LIPSSs, were introduced. It is found that both the melt and
      modification spot-overlap numbers increase with an increase in laser fluence and
      spot-overlap number, contributing to the production of flocculent LIPSSs. LIPSSs
      are obtained with the modification spot-overlap number above 300, and the amount
      of flocculent structures increases with an increase in the peak laser fluence and
      spot-overlap number. Then, considering that the fine adjustment of the melt and
      modification spot-overlop numbers in one-time line scanning is quite difficult,
      the composite structure, of which both LIPSSs and flocculent structures are
      distinct, was optimized using laser line scanning twice. On this basis, a
      characterization test shows the sample full of the flocculent LIPSSs represents
      best antireflectivity with the value around 10% in the waveband between 260 and
      2600 nm (advance 5 times in infrared wavelengths compared to the initial titanium
      surface), and shows the no-stick hydrophobicity with the contact angle of 160
      degrees  and roll-off angle of 25 degrees  because of the pure rutile phase of
      TiO2.

PMID- 28452481
TI  - Reactions of Three Lactones with Cl, OD, and O3: Atmospheric Impact and Trends in
      Furan Reactivity.
AB  - Lactones, cyclic esters of hydroxycarboxylic acids, are interesting biofuel
      candidates as they can be made from cellulosic biomass and have favorable
      physical and chemical properties for distribution and use. The reactions of gamma
      valerolactone (GVL), gamma-crotonolactone (2(5H)-F), and alpha-methyl-gamma
      crotonolactone (3M-2(5H)-F) with Cl, OD, and O3 were investigated in a static
      chamber at 700 Torr and 298 +/- 2 K. The relative rate method was used to
      determine kGVL+Cl = (4.56 +/- 0.51) * 10-11, kGVL+OD = (2.94 +/- 0.41) * 10-11,
      k2(5H)-F+Cl = (2.94 +/- 0.41) * 10-11, k2(5H)-F+OD = (4.06 +/- 0.073) * 10-12,
      k3M-2(5H)-F+Cl = (16.1 +/- 1.8) * 10-11, and k3M-2(5H)-F+OD = (12.6 +/- 0.52) *
      10-12, all rate coefficients in units of cm3 molecule-1 s-1. An absolute rate
      method was used to determine k2(5H)-F+O3 = (6.73 +/- 0.18) * 10-20 and k3M-2(5H)
      F+O3 = (5.42 +/- 1.23) * 10-19 in units of cm3 molecule-1 s-1. Products were
      identified for reactions of the lactones with Cl. In the presence of O2 the
      products are formic acid (HCOOH), formyl chloride (CHClO), and phosgene (CCl2O),
      and also maleic anhydride (C2H2(CO)2O) for 2(5H)-F. In addition both reactions
      produced a number of unidentified products that likely belong to molecules with
      the ring-structure intact. A review of literature data for reactions of other
      furans show that the reactivity of the lactones are generally lower compared to
      that of corresponding compounds without the carbonyl group.

PMID- 28452482
TI  - Hexagonal Boron Nitride Self-Launches Hyperbolic Phonon Polaritons.
AB  - Hexagonal boron nitride (hBN) is a 2D material that supports traveling waves
      composed of material vibrations and light, and is attractive for nanoscale
      optical devices that function in the infrared. However, the only current method
      of launching these traveling waves requires the use of a metal nanostructure.
      Here, we show that the polaritonic waves can be launched into the 2D structure by
      folds within hBN, alone, taking advantage of the intrinsic material properties.
      Our findings suggest that structural continuity between the fold and hBN crystal
      is crucial for creating self-launched waves with a constant phase front. This
      approach offers a single material system to excite the polaritonic modes, and the
      approach is applicable to a broad range of 2D crystals and thus could be useful
      in future characterization.

PMID- 28452484
TI  - Direct Determination of Site-Specific Noncovalent Interaction Strengths of
      Proteins from NMR-Derived Fast Side Chain Motional Parameters.
AB  - A novel approach to accurately determine residue-specific noncovalent interaction
      strengths (xi) of proteins from NMR-measured fast side chain motional parameters
      (Oaxis2) is presented. By probing the environmental sensitivity of side chain
      conformational energy surfaces of individual residues of a diverse set of
      proteins, the microscopic connections between xi, Oaxis2, conformational entropy
      (Sconf), conformational barriers, and rotamer stabilities established here are
      found to be universal among proteins. The results reveal that side chain
      flexibility and conformational entropy of each residue decrease with increasing
      xi and that for each residue type there exists a critical range of xi, determined
      primarily by the mean side chain conformational barriers, within which
      flexibility of any residue can be reversibly tuned from highly flexible (with
      Oaxis2 ~ 0) to highly restricted (with Oaxis2 ~ 1) by increasing xi by ~3
      kcal/mol. Beyond this critical range of xi, both side chain flexibility and
      conformational entropy are insensitive to xi. The interrelationships between
      conformational dynamics, conformational entropy, and noncovalent interactions of
      protein side chains established here open up new avenues to probe perturbation
      induced (for example, ligand-binding, temperature, pressure) changes in fast side
      chain dynamics and thermodynamics of proteins by comparing their conformational
      energy surfaces in the native and perturbed states.

PMID- 28452483
TI  - Solvatochromic Effects on the Absorption Spectrum of 2-Thiocytosine.
AB  - The solvatochromic effects of six different solvents on the UV absorption
      spectrum of 2-thiocytosine have been studied by a combination of experimental and
      theoretical techniques. The steady-state absorption spectra show significant
      shifts of the absorption bands, where in more polar solvents the first absorption
      maximum shifts to higher transition energies and the second maximum to lower
      energies. The observed solvatochromic shifts have been rationalized using three
      popular solvatochromic scales and with high-level multireference quantum
      chemistry calculations including implicit and explicit solvent effects. It has
      been found that the dipole moments of the excited states account for some general
      shifts in the excitation energies, whereas the explicit solvent interactions
      explain the differences in the spectra recorded in the different solvents.

PMID- 28452485
TI  - Systematic Comparison of False-Discovery-Rate-Controlling Strategies for
      Proteogenomic Search Using Spike-in Experiments.
AB  - Proteogenomic searches are useful for novel peptide identification from tandem
      mass spectra. Usually, separate and multistage approaches are adopted to
      accurately control the false discovery rate (FDR) for proteogenomic search. Their
      performance on novel peptide identification has not been thoroughly evaluated,
      however, mainly due to the difficulty in confirming the existence of identified
      novel peptides. We simulated a proteogenomic search using a controlled, spike-in
      proteomic data set. After confirming that the results of the simulated
      proteogenomic search were similar to those of a real proteogenomic search using a
      human cell line data set, we evaluated the performance of six FDR control methods
      global, separate, and multistage FDR estimation, respectively, coupled to a
      target-decoy search and a mixture model-based method-on novel peptide
      identification. The multistage approach showed the highest accuracy for FDR
      estimation. However, global and separate FDR estimation with the mixture model
      based method showed higher sensitivities than others at the same true FDR.
      Furthermore, the mixture model-based method performed equally well when applied
      without or with a reduced set of decoy sequences. Considering different prior
      probabilities for novel and known protein identification, we recommend using
      mixture model-based methods with separate FDR estimation for sensitive and
      reliable identification of novel peptides from proteogenomic searches.

PMID- 28452486
TI  - One-Step Conversion from Core-Shell Metal-Organic Framework Materials to Cobalt
      and Nitrogen Codoped Carbon Nanopolyhedra with Hierarchically Porous Structure
      for Highly Efficient Oxygen Reduction.
AB  - Rational design of porous structure is an effective way to fabricate the
      nonprecious metal electrocatalysts (NPMCs) toward oxygen reduction reaction (ORR)
      with high activity comparable or even superior to Pt-based electrocatalysts.
      Herein, we demonstrate a facile synthetic route to fabricate cobalt and nitrogen
      codoped carbon nanopolyhedra with hierarchically porous structure (Co,N-HCNP) by
      one-step carbonization of core-shell structured ZIF-8@ZIF-67 crystals. The
      resultant Co,N-HCNP electrocatalyst possesses a unique hierarchically
      micro/mesoporous structure with internal micropores and external mesopores, of
      which sufficient exposure and accessibility of ORR active sites can be achieved
      due to the large specific surface area and efficient transport pathway. More
      importantly, the existence of ZIF-8 core in the core-shell structured ZIF-8@ZIF
      67 can promote the homogeneous pyrolysis of ZIF-67 shell, leading to a uniform
      distribution of Co-Nx active sites for Co,N-HCNP. As a result, the well-designed
      Co,N-HCNP electrocatalyst exhibits remarkable ORR activity with a high onset
      potential comparable to the commercial Pt/C, a half-wave potential of 0.855 V (9
      mV more positive than that of Pt/C), and a kinetic current density of 63.84 mA cm
      2 at 0.8 V (2.3-fold enhancement compared with that of Pt/C) in alkaline
      electrolyte. Furthermore, the Co,N-HCNP electrocatalyst also presents outstanding
      electrochemical durability and methanol tolerance in comparison with Pt/C. The
      unique hierarchically porous structure of Co,N-HCNP achieved in this work
      provides a new insight into the design and synthesis of nanoarchitecture with
      targeted pore structure and opens a new avenue for the synthesis of highly
      efficient NPMCs for ORR.

PMID- 28452487
TI  - Two-Step Delamination of Highly Charged, Vermiculite-like Layered Silicates via
      Ordered Heterostructures.
AB  - Because of strong Coulomb interactions, the delamination of charged layered
      materials becomes progressively more difficult with increasing charge density.
      For instance, highly charged sodium fluorohectorite (Na0.6Mg2.4Li0.6Si4O10F2, Na
      Hec) cannot be delaminated directly by osmotic swelling in water because its
      layer charge exceeds the established limit for osmotic swelling of 0.55 per
      formula unit Si4O10F2. Quite surprisingly, we found that this hectorite at the
      border of the smectite and vermiculite group can, however, be utterly delaminated
      into 1-nm-thick platelets with a high aspect ratio (24 000) in a two-step
      process. The hectorite is first converted by partial ion exchange into a one
      dimensionally ordered, interstratified heterostructure with strictly alternating
      Na+ and n-butylammonium (C4) interlayers. This heterostructure then spontaneously
      delaminates into uniform single layers upon immersion in water whereas neither of
      the homoionic phases (Na-Hec and C4-Hec) swells osmotically. The delamination of
      more highly charged synthetic layered silicates is a key step to push the aspect
      ratio beyond the current limits.

PMID- 28452489
TI  - Construction of Hierarchical Fouling Resistance Surfaces onto Poly(vinylidene
      fluoride) Membranes for Combating Membrane Biofouling.
AB  - Owing to the highly hydrophobic nature, fluoropolymer membranes usually suffer
      from serious fouling problem, and therefore largely limited their practical
      applications. Also, the development of environmentally benign and nonreleasing
      antifouling coatings onto the inert fluoropolymer membranes remains a great
      challenge and is of prime importance for various scientific interests and
      industrial applications. In the present work, a facile and effective approach for
      the construction of hierarchical fouling resistance surfaces onto the
      poly(vinylidene fluoride) (PVDF) membranes was developed. Graft copolymers of
      PVDF with poly(hyperbranched polyglycerol methacrylamide) side chains (PVDF-g
      PHPGMA copolymers) were synthesized via reversible addition-fragmentation chain
      transfer (RAFT) graft copolymerization of pentafluorophenyl methacrylate (PFMA)
      with the ozone-preactivated PVDF, followed by activated ester-amine reaction of
      PPFMA chains with amino-terminated hyperbranched polyglycerol (HPG-NH2). The
      copolymers could be simply processed into microfiltration (MF) membranes with
      surface-tethered PHPGMA side chains on the membrane and pore surfaces by
      nonsolvent induced phase inversion. Furthermore, the PVDF-g-PHPGMA-g-PSBMA
      membrane was prepared via surface-initiated atom transfer radical polymerization
      (SI-ATRP) of zwitterionic monomer, N-(3-sulfopropyl)-N-(methacryloxyethyl)-N,N
      dimethylammonium betaine (SBMA) from the PVDF-g-PHPGMA membrane and pore
      surfaces. Arise from a synergistic effect of the dendritic architecture of PHPGMA
      branches and "superhydrophilic" nature of PSBMA brushes, the PVDF-g-PHPGMA-g
      PSBMA membranes exhibit superior resistance to protein and bacteria adhesion with
      insignificant cytotoxicity effects, making the membranes potentially useful for
      water treatment and biomedical applications. One may find the present study a
      general and effective method for the fabrication of antifouling fluoropolymer
      membranes in a controllable and green manner.

PMID- 28452490
TI  - Synthesis of a Family of Highly Substituted Porphyrin Thioethers via Nitro
      Displacement in 2,3,7,8,12,13,17,18-Octaethyl-5,10,15,20-tetranitroporphyrin.
AB  - A series of highly substituted porphyrin thioethers was synthesized from
      2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetranitroporphyrin (H2OETNP). The
      reactions proceeded via a SNAr mechanism with a broad range of aromatic thiols in
      the presence of a base. This is a rapid way to prepare a large variety of meso
      substituted porphyrins from only one precursor. Single crystal X-ray analysis
      revealed that these new porphyrin thioethers are highly distorted, exhibiting
      conformational properties that are distinctive of both meso-sulfur substitution
      and steric overcrowding in general. Additionally, denitration of H2OETNP under
      basic conditions was investigated, yielding products of stepwise desubstitution.
      This allowed a comparative X-ray crystallographic study to delineate the
      successive structural effects of an increasing degree of nitro substitution in
      the complete series of nitro-substituted octaethylporphyrins.

PMID- 28452491
TI  - A Reaction Cycle for Octahedral Tungsten Iodide Clusters.
AB  - A reaction cycle is shown for octahedral tungsten iodide compounds. The thermal
      transformation of W6I16 (W6I12.2I2) via release of iodine proceeds via the new
      W6I13 (W6I12.xI2 with 0 < x <= 1/2) to yield a new modification of W6I12, denoted
      as alpha-W6I12. When heated, alpha-W6I12 is converted into the known (beta
      )W6I12. The reaction of (beta-)W6I12 with I2 leads to the formation of the
      starting compound W6I16. The new compounds W6I13 (W6I12.xI2 with 0 < x <= 1/2)
      and alpha-W6I12 are structurally characterized by powder and single-crystal X-ray
      diffraction techniques. The thermal decomposition of W6I16 and the monotropic
      phase transition of alpha-W6I12 into beta-W6I12 are examined by differential
      scanning calorimetry measurements.

PMID- 28452488
TI  - Metabolomics Study of the Effects of Inflammation, Hypoxia, and High Glucose on
      Isolated Human Pancreatic Islets.
AB  - The transplantation of human pancreatic islets is a therapeutic possibility for a
      subset of type 1 diabetic patients who experience severe hypoglycemia. Pre- and
      post-transplantation loss in islet viability and function, however, is a major
      efficacy-limiting impediment. To investigate the effects of inflammation and
      hypoxia, the main obstacles hampering the survival and function of isolated,
      cultured, and transplanted islets, we conducted a comprehensive metabolomics
      evaluation of human islets in parallel with dynamic glucose-stimulated insulin
      release (GSIR) perifusion studies for functional evaluation. Metabolomics
      profiling of media and cell samples identified a total of 241 and 361
      biochemicals, respectively. Metabolites that were altered in highly significant
      manner in both included, for example, kynurenine, kynurenate, citrulline, and
      mannitol/sorbitol under inflammation (all elevated) plus lactate (elevated) and N
      formylmethionine (depressed) for hypoxia. Dynamic GSIR experiments, which capture
      both first- and second-phase insulin release, found severely depressed insulin
      secretion under hypoxia, whereas elevated baseline and stimulated insulin
      secretion was measured for islet exposed to the inflammatory cytokine cocktail
      (IL-1beta, IFN-gamma, and TNF-alpha). Because of the uniquely large changes
      observed in kynurenine and kynurenate, they might serve as potential biomarkers
      of islet inflammation, and indoleamine-2,3-dioxygenase on the corresponding
      pathway could be a worthwhile therapeutic target to dampen inflammatory effects.

PMID- 28452492
TI  - Magnetic Relaxation Dynamics of a Centrosymmetric Dy2 Single-Molecule Magnet
      Triggered by Magnetic-Site Dilution and External Magnetic Field.
AB  - A centrosymmetric Dy2 single-molecule magnet (SMM) and its doped diamagnetic
      yttrium analogues, Dy0.19Y1.81 and Dy0.10Y1.90, were solvothermally synthesized
      to investigate the effects of intramolecular exchange coupling and quantum
      tunneling of magnetization (QTM) on the magnetic relaxation dynamics. Constructed
      from two hula-hoop-like DyIII ions and a pair of phenoxido groups, the
      antiferromagnetically coupled Dy2 exhibits a thermal-activated zero-field
      effective energy barrier (Ueff) of 277.7 K and negligible hysteresis loop at 2.0
      K. The doping of a diamagnetic YIII matrix with 90.5% and 95.0% molar ratios
      reveals the single-ion origin of the Orbach channel, increases the relaxation
      time by partially quenching the QTM process, and induces an open hysteresis loop
      until 5.0 K. In contrast, an optimal dc field of 1.0 kOe improves the barrier
      height up to 290.1 K through complete elimination of the QTM and delays the
      relaxation time of the direct relaxation pathway. More interestingly, the
      collaborative dual effects of magnetic-site dilution and external magnetic field
      make the effective energy barrier and relaxation time increase 8.1% and 49 times,
      respectively. Thus, the overall magnetization dynamics of the Dy2 system
      systematically elaborate the inherent interplay of the QTM and Orbach processes
      on the effective energy barrier, highlighting the vital role of the relaxation
      time on the coercive hysteresis loop.

PMID- 28452493
TI  - Controlling the Conductance of a Graphene-Molecule Nanojunction by Proton
      Transfer.
AB  - The possibility of using single molecule junctions as components of
      nanoelectronic devices has motivated intensive experimental and theoretical
      research on the underlying transport mechanism in these systems. In this Letter,
      we investigate from a theoretical perspective intramolecular proton transfer
      reactions as a mechanism for controlling the conductance state of graphene-based
      molecular junctions. Employing a methodology that combines first-principles
      electronic structure methods with transport approaches, we show that the proton
      transfer reaction proceeds via a stepwise mechanism, giving rise to several
      tautomers with different conductance states. The analysis reveals that the
      relative stability of the tautomers as well as the energy barrier for their
      interconversion can be controlled by means of an external electrostatic field,
      which provides a mechanism for switching the nanojunction.

PMID- 28452494
TI  - Sulfur Vapor-Infiltrated 3D Carbon Nanotube Foam for Binder-Free High Areal
      Capacity Lithium-Sulfur Battery Composite Cathodes.
AB  - Here, we demonstrate a strategy to produce high areal loading and areal capacity
      sulfur cathodes by using vapor-phase infiltration of low-density carbon nanotube
      (CNT) foams preformed by solution processing and freeze-drying. Vapor-phase
      capillary infiltration of sulfur into preformed and binder-free low-density CNT
      foams leads to a mass loading of ~79 wt % arising from interior filling and
      coating of CNTs with sulfur while preserving conductive CNT-CNT junctions that
      sustain electrical accessibility through the thick foam. Sulfur cathodes are then
      produced by mechanically compressing these foams into dense composites (rho > 0.2
      g/cm3), revealing specific capacity of 1039 mAh/gS at 0.1 C, high sulfur areal
      loading of 19.1 mg/cm2, and high areal capacity of 19.3 mAh/cm2. This work
      highlights a technique broadly adaptable to a diverse group of nanostructured
      building blocks where preformed low-density materials can be vapor infiltrated
      with sulfur, mechanically compressed, and exhibit simultaneous high areal and
      gravimetric storage properties. This provides a route for scalable, low-cost, and
      high-energy density sulfur cathodes based on conventional solid electrode
      processing routes.

PMID- 28452495
TI  - Recognition of Viologen Derivatives in Water by N-Alkyl Ammonium Resorcinarene
      Chlorides.
AB  - Three water-soluble N-alkyl ammonium resorcinarene chlorides decorated with
      terminal hydroxyl groups at the lower rims were synthesized and characterized.
      The receptors were decorated at the upper rim with either terminal hydroxyl,
      rigid cyclohexyl, or flexible benzyl groups. The binding affinities of these
      receptors toward three viologen derivatives, two of which possess an acetylmethyl
      group attached to one of the pyridine nitrogens, in water were investigated via
      1H NMR spectroscopy, fluorescence spectroscopy, and isothermal titration
      calorimetry (ITC). ITC quantification of the binding process gave association
      constants of up to 103 M-1. Analyses reveal a spontaneous binding process which
      are all exothermic and are both enthalpy and entropy driven.

PMID- 28452497
TI  - Enhancing the Charging Power of Quantum Batteries.
AB  - Can collective quantum effects make a difference in a meaningful thermodynamic
      operation? Focusing on energy storage and batteries, we demonstrate that quantum
      mechanics can lead to an enhancement in the amount of work deposited per unit
      time, i.e., the charging power, when N batteries are charged collectively. We
      first derive analytic upper bounds for the collective quantum advantage in
      charging power for two choices of constraints on the charging Hamiltonian. We
      then demonstrate that even in the absence of quantum entanglement this advantage
      can be extensive. For our main result, we provide an upper bound to the
      achievable quantum advantage when the interaction order is restricted; i.e., at
      most k batteries are interacting. This constitutes a fundamental limit on the
      advantage offered by quantum technologies over their classical counterparts.

PMID- 28452496
TI  - Thermodynamic Paradigm for Solution Demixing Inspired by Nuclear Transport in
      Living Cells.
AB  - Living cells display a remarkable capacity to compartmentalize their functional
      biochemistry. A particularly fascinating example is the cell nucleus. Exchange of
      macromolecules between the nucleus and the surrounding cytoplasm does not involve
      traversing a lipid bilayer membrane. Instead, large protein channels known as
      nuclear pores cross the nuclear envelope and regulate the passage of other
      proteins and RNA molecules. Beyond simply gating diffusion, the system of nuclear
      pores and associated transport receptors is able to generate substantial
      concentration gradients, at the energetic expense of guanosine triphosphate
      hydrolysis. In contrast to conventional approaches to demixing such as reverse
      osmosis and dialysis, the biological system operates continuously, without
      application of cyclic changes in pressure or solvent exchange. Abstracting the
      biological paradigm, we examine this transport system as a thermodynamic machine
      of solution demixing. Building on the construct of free energy transduction and
      biochemical kinetics, we find conditions for the stable operation and
      optimization of the concentration gradients as a function of dissipation in the
      form of entropy production.

PMID- 28452498
TI  - Direct Evidence for Octupole Deformation in ^{146}Ba and the Origin of Large E1
      Moment Variations in Reflection-Asymmetric Nuclei.
AB  - Despite the more than 1 order of magnitude difference between the measured dipole
      moments in ^{144}Ba and ^{146}Ba, the octupole correlations in ^{146}Ba are found
      to be as strong as those in ^{144}Ba with a similarly large value of B(E3;3^{-}
      >0^{+}) determined as 48(+21-29)  W.u. The new results not only establish
      unambiguously the presence of a region of octupole deformation centered on these
      neutron-rich Ba isotopes, but also manifest the dependence of the electric dipole
      moments on the occupancy of different neutron orbitals in nuclei with enhanced
      octupole strength, as revealed by fully microscopic calculations.

PMID- 28452499
TI  - Flow Navigation by Smart Microswimmers via Reinforcement Learning.
AB  - Smart active particles can acquire some limited knowledge of the fluid
      environment from simple mechanical cues and exert a control on their preferred
      steering direction. Their goal is to learn the best way to navigate by exploiting
      the underlying flow whenever possible. As an example, we focus our attention on
      smart gravitactic swimmers. These are active particles whose task is to reach the
      highest altitude within some time horizon, given the constraints enforced by
      fluid mechanics. By means of numerical experiments, we show that swimmers indeed
      learn nearly optimal strategies just by experience. A reinforcement learning
      algorithm allows particles to learn effective strategies even in difficult
      situations when, in the absence of control, they would end up being trapped by
      flow structures. These strategies are highly nontrivial and cannot be easily
      guessed in advance. This Letter illustrates the potential of reinforcement
      learning algorithms to model adaptive behavior in complex flows and paves the way
      towards the engineering of smart microswimmers that solve difficult navigation
      problems.

PMID- 28452500
TI  - Quantum Corrections in Nanoplasmonics: Shape, Scale, and Material.
AB  - The classical treatment of plasmonics is insufficient at the nanometer-scale due
      to quantum mechanical surface phenomena. Here, an extension of the classical
      paradigm is reported which rigorously remedies this deficiency through the
      incorporation of first-principles surface response functions-the Feibelman d
      parameters-in general geometries. Several analytical results for the leading
      order plasmonic quantum corrections are obtained in a first-principles setting;
      particularly, a clear separation of the roles of shape, scale, and material is
      established. The utility of the formalism is illustrated by the derivation of a
      modified sum rule for complementary structures, a rigorous reformulation of
      Kreibig's phenomenological damping prescription, and an account of the small
      scale resonance shifting of simple and noble metal nanostructures.

PMID- 28452501
TI  - Dispersion-Induced Beam Instability in Circular Accelerators.
AB  - The envelope instability near the 90 degrees  phase advance in periodically
      focused space charge dominated beams is a well-known phenomenon in linear
      transport sections or linacs. The corresponding stop band is usually avoided
      because of the resulting strong mismatch oscillations and beam loss. We show that
      in circular accelerators or transport sections including bending magnets the
      instability is modified due to the effect of dispersion. Using the two
      dimensional envelope equations extended by the dispersion equation we identify an
      additional stop band above 120 degrees . For periodic focusing the stop band
      results from the confluence of an envelope mode with the newly identified
      coherent dispersion mode. Results from perturbation theory are compared with the
      full envelope model and particle-in-cell simulation, which all show good
      agreement. The newly identified mode has several implications and applications
      for the characterization of intense beams in circular machines.

PMID- 28452503
TI  - Scale Invariance in Lateral Head Scans During Spatial Exploration.
AB  - Universality connects various natural phenomena through physical principles
      governing their dynamics, and has provided broadly accepted answers to many
      complex questions, including information processing in neuronal systems. However,
      its significance in behavioral systems is still elusive. Lateral head scanning
      (LHS) behavior in rodents might contribute to spatial navigation by actively
      managing (optimizing) the available sensory information. Our findings of scale
      invariant distributions in LHS lifetimes, interevent intervals and event
      magnitudes, provide evidence for the first time that the optimization takes place
      at a critical point in LHS dynamics. We propose that the LHS behavior is
      responsible for preprocessing of the spatial information content, critical for
      subsequent foolproof encoding by the respective downstream neural networks.

PMID- 28452502
TI  - Matching Microscopic and Macroscopic Responses in Glasses.
AB  - We first reproduce on the Janus and Janus II computers a milestone experiment
      that measures the spin-glass coherence length through the lowering of free-energy
      barriers induced by the Zeeman effect. Secondly, we determine the scaling
      behavior that allows a quantitative analysis of a new experiment reported in the
      companion Letter [S. Guchhait and R. Orbach, Phys. Rev. Lett. 118, 157203
      (2017)].PRLTAO0031-900710.1103/PhysRevLett.118.157203 The value of the coherence
      length estimated through the analysis of microscopic correlation functions turns
      out to be quantitatively consistent with its measurement through macroscopic
      response functions. Further, nonlinear susceptibilities, recently measured in
      glass-forming liquids, scale as powers of the same microscopic length.

PMID- 28452504
TI  - Depletion of Intense Fields.
AB  - The interaction of charged particles and photons with intense electromagnetic
      fields gives rise to multiphoton Compton and Breit-Wheeler processes. These are
      usually described in the framework of the external field approximation, where the
      electromagnetic field is assumed to have infinite energy. However, the
      multiphoton nature of these processes implies the absorption of a significant
      number of photons, which scales as the external field amplitude cubed. As a
      result, the interaction of a highly charged electron bunch with an intense laser
      pulse can lead to significant depletion of the laser pulse energy, thus rendering
      the external field approximation invalid. We provide relevant estimates for this
      depletion and find it to become important in the interaction between fields of
      amplitude a_{0}~10^{3} and electron bunches with charges of the order of 10 nC.

PMID- 28452505
TI  - Nonlinear Rheology in a Model Biological Tissue.
AB  - The rheological response of dense active matter is a topic of fundamental
      importance for many processes in nature such as the mechanics of biological
      tissues. One prominent way to probe mechanical properties of tissues is to study
      their response to externally applied forces. Using a particle-based model
      featuring random apoptosis and environment-dependent division rates, we evidence
      a crossover from linear flow to a shear-thinning regime with an increasing shear
      rate. To rationalize this nonlinear flow we derive a theoretical mean-field
      scenario that accounts for the interplay of mechanical and active noise in local
      stresses. These noises are, respectively, generated by the elastic response of
      the cell matrix to cell rearrangements and by the internal activity.

PMID- 28452506
TI  - Distinguishability and Many-Particle Interference.
AB  - Quantum interference of two independent particles in pure quantum states is fully
      described by the particles' distinguishability: the closer the particles are to
      being identical, the higher the degree of quantum interference. When more than
      two particles are involved, the situation becomes more complex and interference
      capability extends beyond pairwise distinguishability, taking on a surprisingly
      rich character. Here, we study many-particle interference using three photons. We
      show that the distinguishability between pairs of photons is not sufficient to
      fully describe the photons' behavior in a scattering process, but that a
      collective phase, the triad phase, plays a role. We are able to explore the full
      parameter space of three-photon interference by generating heralded single
      photons and interfering them in a fiber tritter. Using multiple degrees of
      freedom-temporal delays and polarization-we isolate three-photon interference
      from two-photon interference. Our experiment disproves the view that pairwise two
      photon distinguishability uniquely determines the degree of nonclassical many
      particle interference.

PMID- 28452507
TI  - Fundamental Costs in the Production and Destruction of Persistent Polymer Copies.
AB  - Producing a polymer copy of a polymer template is central to biology, and
      effective copies must persist after template separation. We show that this
      separation has three fundamental thermodynamic effects. First, polymer-template
      interactions do not contribute to overall reaction thermodynamics and hence
      cannot drive the process. Second, the equilibrium state of the copied polymer is
      template independent and so additional work is required to provide specificity.
      Finally, the mixing of copies from distinct templates makes correlations between
      template and copy sequences unexploitable, combining with copying inaccuracy to
      reduce the free energy stored in a polymer ensemble. These basic principles set
      limits on the underlying costs and resource requirements, and suggest design
      principles, for autonomous copying and replication in biological and synthetic
      systems.

PMID- 28452508
TI  - Publisher's Note: Quantized Vortices and Four-Component Superfluidity of
      Semiconductor Excitons [Phys. Rev. Lett. 118, 127402 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.127402.

PMID- 28452509
TI  - Forecasting Tidal Disruption Events for Binary Black Holes with an Outer
      Tertiary.
AB  - We discuss the gravitational wave (GW) emission and the orbital evolution of a
      hierarchical triple system composed of an inner binary black hole (BBH) and an
      outer tertiary. Depending on the kick velocity at the merger, the merged BBH
      could tidally disrupt the tertiary. Even though the fraction of BBH mergers
      accompanied by such disruptions is expected to be much smaller than unity, the
      existence of a tertiary and its basic parameters (e.g., semimajor axis, projected
      mass) can be examined for more than 10^{3} BBHs with the follow-on missions to
      the space GW detector LISA. This allows us to efficiently prescreen the targets
      for the follow-up searches for the tidal disruption events (TDEs). The TDE
      probability would be significantly higher for triple systems with aligned orbital
      and spin-angular momenta, compared with random configurations.

PMID- 28452510
TI  - Pulsar Timing Array Based Search for Supermassive Black Hole Binaries in the
      Square Kilometer Array Era.
AB  - The advent of next generation radio telescope facilities, such as the Square
      Kilometer Array (SKA), will usher in an era where a pulsar timing array (PTA)
      based search for gravitational waves (GWs) will be able to use hundreds of well
      timed millisecond pulsars rather than the few dozens in existing PTAs. A
      realistic assessment of the performance of such an extremely large PTA must take
      into account the data analysis challenge posed by an exponential increase in the
      parameter space volume due to the large number of so-called pulsar phase
      parameters. We address this problem and present such an assessment for isolated
      supermassive black hole binary (SMBHB) searches using a SKA era PTA containing
      10^{3} pulsars. We find that an all-sky search will be able to confidently detect
      nonevolving sources with a redshifted chirp mass of 10^{10}  M_{?} out to a
      redshift of about 28 (corresponding to a rest-frame chirp mass of 3.4*10^{8} 
      M_{?}). We discuss the important implications that the large distance reach of a
      SKA era PTA has on GW observations from optically identified SMBHB candidates. If
      no SMBHB detections occur, a highly unlikely scenario in the light of our
      results, the sky-averaged upper limit on strain amplitude will be improved by
      about 3 orders of magnitude over existing limits.

PMID- 28452511
TI  - Ab Initio Description of Open-Shell Nuclei: Merging No-Core Shell Model and In
      Medium Similarity Renormalization Group.
AB  - We merge two successful ab initio nuclear-structure methods, the no-core shell
      model (NCSM) and the multireference in-medium similarity renormalization group
      (IM-SRG) to define a new many-body approach for the comprehensive description of
      ground and excited states of closed and open-shell nuclei. Building on the key
      advantages of the two methods-the decoupling of excitations at the many-body
      level in the IM-SRG and the access to arbitrary nuclei, eigenstates, and
      observables in the NCSM-their combination enables fully converged no-core
      calculations for an unprecedented range of nuclei and observables at moderate
      computational cost. We present applications in the carbon and oxygen isotopic
      chains, where conventional NCSM calculations are still feasible and provide an
      important benchmark. The efficiency and rapid convergence of the new approach
      make it ideally suited for ab initio studies of the complete spectroscopy of
      nuclei up into the medium-mass regime.

PMID- 28452512
TI  - Doping Dependence of Collective Spin and Orbital Excitations in the Spin-1
      Quantum Antiferromagnet La_{2-x}Sr_{x}NiO_{4} Observed by X Rays.
AB  - We report the first empirical demonstration that resonant inelastic x-ray
      scattering (RIXS) is sensitive to collective magnetic excitations in S=1 systems
      by probing the Ni L_{3} edge of La_{2-x}Sr_{x}NiO_{4} (x=0, 0.33, 0.45). The
      magnetic excitation peak is asymmetric, indicating the presence of single and
      multi-spin-flip excitations. As the hole doping level is increased, the zone
      boundary magnon energy is suppressed at a much larger rate than that in hole
      doped cuprates. Based on the analysis of the orbital and charge excitations
      observed by RIXS, we argue that this difference is related to the orbital
      character of the doped holes in these two families. This work establishes RIXS as
      a probe of fundamental magnetic interactions in nickelates opening the way
      towards studies of heterostructures and ultrafast pump-probe experiments.

PMID- 28452514
TI  - Creation and Manipulation of Stable Dark Solitons and Vortices in Microcavity
      Polariton Condensates.
AB  - Solitons and vortices obtain widespread attention in different physical systems
      as they offer potential use in information storage, processing, and
      communication. In exciton-polariton condensates in semiconductor microcavities,
      solitons and vortices can be created optically. However, dark solitons are
      unstable and vortices cannot be spatially controlled. In the present work we
      demonstrate the existence of stable dark solitons and vortices under nonresonant
      incoherent excitation of a polariton condensate with a simple spatially periodic
      pump. In one dimension, we show that an additional coherent light pulse can be
      used to create or destroy a dark soliton in a controlled manner. In two
      dimensions we demonstrate that a coherent light beam can be used to move a vortex
      to a specific position on the lattice or be set into motion by simply switching
      the periodic pump structure from two-dimensional (lattice) to one-dimensional
      (stripes). Our theoretical results open up exciting possibilities for optical on
      demand generation and control of dark solitons and vortices in polariton
      condensates.

PMID- 28452515
TI  - Classical Fractals and Quantum Chaos in Ultracold Dipolar Collisions.
AB  - We examine a dipolar-gas model to address fundamental issues regarding the
      correspondence between classical chaos and quantum observations in ultracold
      dipolar collisions. The theoretical model consists of a short-range Lennard-Jones
      potential well with an anisotropic, long-range dipole-dipole interaction between
      two atoms. Both the classical and quantum dynamics are explored for the same
      Hamiltonian of the system. The classical chaotic scattering is revealed by the
      fractals developed in the scattering function (defined as the final atom
      separation as a function of initial conditions), while the quantum chaotic
      features lead to the repulsion of the eigenphases from the corresponding quantum
      S matrix. The nearest-eigenphase-spacing statistics have an intermediate behavior
      between the Poisson and the Wigner-Dyson distributions. The character of the
      distribution can be controlled by changing an effective Planck constant or the
      dipole moment. The degree of quantum chaos shows a good correspondence with the
      overall average of the classical scattering function. The results presented here
      also provide helpful insights for understanding the role of the inherent dipole
      dipole interaction in the currently ongoing experiments on ultracold collisions
      of highly magnetic atoms.

PMID- 28452516
TI  - Anomalous Quantum Correlations of Squeezed Light.
AB  - Three different noise moments of field strength, intensity, and their
      correlations are simultaneously measured. For this purpose a homodyne cross
      correlation measurement [1] is implemented by superimposing the signal field and
      a weak local oscillator on an unbalanced beam splitter. The relevant information
      is obtained via the intensity noise correlation of the output modes. Detection
      details like quantum efficiencies or uncorrelated dark noise are meaningless for
      our technique. Yet unknown insight in the quantumness of a squeezed signal field
      is retrieved from the anomalous moment, correlating field strength with intensity
      noise. A classical inequality including this moment is violated for almost all
      signal phases. Precognition on quantum theory is superfluous, as our analysis is
      solely based on classical physics.

PMID- 28452517
TI  - Direct Measurement of Sub-10 fs Relativistic Electron Beams with Ultralow
      Emittance.
AB  - Ultralow emittance (<=20  nm, normalized) electron beams with 10^{5} electrons
      per bunch are obtained by tightly focusing an ultrafast (~100  fs) laser pulse on
      the cathode of a 1.6 cell radio frequency photoinjector. Taking advantage of the
      small initial longitudinal emittance, a downstream velocity bunching cavity is
      used to compress the beam to <10  fs rms bunch length. The measurement is
      performed using a thick high-voltage deflecting cavity which is shown to be well
      suited to measure ultrashort durations of bunching beams, provided that the beam
      reaches a ballistic longitudinal focus at the cavity center.

PMID- 28452518
TI  - Single-Shot Readout of a Nuclear Spin Weakly Coupled to a Nitrogen-Vacancy Center
      at Room Temperature.
AB  - Single-shot readout of qubits is required for scalable quantum computing. Nuclear
      spins are superb quantum memories due to their long coherence time, but are
      difficult to be read out in a single shot due to their weak interaction with
      probes. Here we demonstrate single-shot readout of a weakly coupled ^{13}C
      nuclear spin at room temperature, which is unresolvable in traditional protocols.
      States of the weakly coupled nuclear spin are trapped and read out projectively
      by sequential weak measurements, which are implemented by dynamical decoupling
      pulses. A nuclear spin coupled to the nitrogen-vacancy (NV) center with strength
      330 kHz is read out in 200 ms with a fidelity of 95.5%. This work provides a
      general protocol for single-shot readout of weakly coupled qubits at room
      temperature and therefore largely extends the range of physical systems for
      scalable quantum computing.

PMID- 28452519
TI  - Nonlocal Parity Order in the Two-Dimensional Mott Insulator.
AB  - The Mott insulator is characterized by having small deviations around the
      (integer) average particle density n, with pairs with n-1 and n+1 particles
      forming bound states. In one dimension, the effect is captured by a nonzero value
      of a nonlocal "string" of parities, which instead vanishes in the superfluid
      phase where density fluctuations are large. Here, we investigate the interaction
      induced transition from the superfluid to the Mott insulator, in the paradigmatic
      Bose Hubbard model at n=1. By means of quantum Monte Carlo simulations and finite
      size scaling analysis on L*M ladders, we explore the behavior of "brane" parity
      operators from one dimension (i.e., M=1 and L->infinity) to two dimensions (i.e.,
      M->infinity and L->infinity). We confirm the conjecture that, adopting a standard
      definition, their average value decays to zero in two dimensions also in the
      insulating phase, evaluating the scaling factor of the "perimeter law" [S. P.
      Rath et al., Ann. Phys. (Berlin) 334, 256 (2013)ANPYA20003
      380410.1016/j.aop.2013.04.006]. Upon introducing a further phase in the brane
      parity, we show that its expectation value becomes nonzero in the insulator,
      while still vanishing at the transition to the superfluid phase. These quantities
      are directly accessible to experimental measures, thus providing an insightful
      signature of the Mott insulator.

PMID- 28452513
TI  - Measurement of the Neutrino Mixing Angle theta_{23} in NOvA.
AB  - This Letter reports new results on muon neutrino disappearance from NOvA, using a
      14 kton detector equivalent exposure of 6.05*10^{20} protons on target from the
      NuMI beam at the Fermi National Accelerator Laboratory. The measurement probes
      the muon-tau symmetry hypothesis that requires maximal theta_{23} mixing
      (theta_{23}=pi/4). Assuming the normal mass hierarchy, we find
      Deltam_{32}^{2}=(2.67+/-0.11)*10^{-3}  eV^{2} and sin^{2}theta_{23} at the two
      statistically degenerate values 0.404_{-0.022}^{+0.030} and 0.624_{
      0.030}^{+0.022}, both at the 68% confidence level. Our data disfavor the maximal
      mixing scenario with 2.6sigma significance.

PMID- 28452520
TI  - Dynamic Substrate for the Physical Encoding of Sensory Information in Bat
      Biosonar.
AB  - Horseshoe bats have dynamic biosonar systems with interfaces for ultrasonic
      emission (reception) that change shape while diffracting the outgoing (incoming)
      sound waves. An information-theoretic analysis based on numerical and physical
      prototypes shows that these shape changes add sensory information (mutual
      information between distant shape conformations <20%), increase the number of
      resolvable directions of sound incidence, and improve the accuracy of direction
      finding. These results demonstrate that horseshoe bats have a highly effective
      substrate for dynamic encoding of sensory information.

PMID- 28452521
TI  - Comment on "New Ground-State Crystal Structure of Elemental Boron".

PMID- 28452522
TI  - Imaging Local Diffusive Dynamics Using Diffusion Exchange Spectroscopy MRI.
AB  - The movement of water between microenvironments presents a central challenge in
      the physics of soft matter and porous media. Diffusion exchange spectroscopy
      (DEXSY) is a powerful 2D nuclear magnetic resonance method for measuring such
      exchange, yet it is rarely used because of its long scan time requirements.
      Moreover, it has never been combined with magnetic resonance imaging (MRI). Using
      probability theory, we vastly reduce the required data, making DEXSY MRI feasible
      for the first time. Experiments are performed on a composite nerve tissue phantom
      with restricted and free water-exchanging compartments.

PMID- 28452523
TI  - Measurement-Device-Independent Approach to Entanglement Measures.
AB  - Within the context of semiquantum nonlocal games, the trust can be removed from
      the measurement devices in an entanglement-detection procedure. Here, we show
      that a similar approach can be taken to quantify the amount of entanglement. To
      be specific, first, we show that in this context, a small subset of semiquantum
      nonlocal games is necessary and sufficient for entanglement detection in the
      local operations and classical communication paradigm. Second, we prove that the
      maximum payoff for these games is a universal measure of entanglement which is
      convex and continuous. Third, we show that for the quantification of negative
      partial-transpose entanglement, this subset can be further reduced down to a
      single arbitrary element. Importantly, our measure is measurement device
      independent by construction and operationally accessible. Finally, our approach
      straightforwardly extends to quantify the entanglement within any partitioning of
      multipartite quantum states.

PMID- 28452524
TI  - Dipole of the Epoch of Reionization 21-cm Signal.
AB  - The motion of the Solar System with respect to the cosmic rest frame modulates
      the monopole of the epoch of reionization 21-cm signal into a dipole. This dipole
      has a characteristic frequency dependence that is dominated by the frequency
      derivative of the monopole signal. We argue that although the signal is weaker by
      a factor of ~100, there are significant benefits in measuring the dipole. Most
      importantly, the direction of the cosmic velocity vector is known exquisitely
      well from the cosmic microwave background and is not aligned with the galaxy
      velocity vector that modulates the foreground monopole. Moreover, an experiment
      designed to measure a dipole can rely on differencing patches of the sky rather
      than making an absolute signal measurement, which helps with some systematic
      effects.

PMID- 28452525
TI  - Two-Dimensional Melting of Colloidal Hard Spheres.
AB  - We study the melting of quasi-two-dimensional colloidal hard spheres by
      considering a tilted monolayer of particles in sedimentation-diffusion
      equilibrium. In particular, we measure the equation of state from the density
      profiles and use time-dependent and height-resolved correlation functions to
      identify the liquid, hexatic, and crystal phases. We find that the liquid-hexatic
      transition is first order and that the hexatic-crystal transition is continuous.
      Furthermore, we directly measure the width of the liquid-hexatic coexistence gap
      from the fluctuations of the corresponding interface, and thereby experimentally
      establish the full phase behavior of hard disks.

PMID- 28452526
TI  - Huygens-Fresnel Acoustic Interference and the Development of Robust Time-Averaged
      Patterns from Traveling Surface Acoustic Waves.
AB  - Periodic pattern generation using time-averaged acoustic forces conventionally
      requires the intersection of counterpropagating wave fields, where suspended
      micro-objects in a microfluidic system collect along force potential minimizing
      nodal or antinodal lines. Whereas this effect typically requires either multiple
      transducer elements or whole channel resonance, we report the generation of
      scalable periodic patterning positions without either of these conditions. A
      single propagating surface acoustic wave interacts with the proximal channel wall
      to produce a knife-edge effect according to the Huygens-Fresnel principle, where
      these cylindrically propagating waves interfere with classical wave fronts
      emanating from the substrate. We simulate these conditions and describe a model
      that accurately predicts the lateral spacing of these positions in a robust and
      novel approach to acoustic patterning.

PMID- 28452527
TI  - Hybrid Quantum-Classical Approach to Quantum Optimal Control.
AB  - A central challenge in quantum computing is to identify more computational
      problems for which utilization of quantum resources can offer significant
      speedup. Here, we propose a hybrid quantum-classical scheme to tackle the quantum
      optimal control problem. We show that the most computationally demanding part of
      gradient-based algorithms, namely, computing the fitness function and its
      gradient for a control input, can be accomplished by the process of evolution and
      measurement on a quantum simulator. By posing queries to and receiving answers
      from the quantum simulator, classical computing devices update the control
      parameters until an optimal control solution is found. To demonstrate the quantum
      classical scheme in experiment, we use a seven-qubit nuclear magnetic resonance
      system, on which we have succeeded in optimizing state preparation without
      involving classical computation of the large Hilbert space evolution.

PMID- 28452528
TI  - Erratum: New Ground-State Crystal Structure of Elemental Boron [Phys. Rev. Lett.
      117, 085501 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.117.085501.

PMID- 28452529
TI  - Effect of Cell Aspect Ratio on Swarming Bacteria.
AB  - Swarming bacteria collectively migrate on surfaces using flagella, forming
      dynamic whirls and jets that consist of millions of individuals. Because some
      swarming bacteria elongate prior to actual motion, cell aspect ratio may play a
      significant role in the collective dynamics. Extensive research on self-propelled
      rodlike particles confirms that elongation promotes alignment, strongly affecting
      the dynamics. Here, we study experimentally the collective dynamics of variants
      of swarming Bacillus subtilis that differ in length. We show that the swarming
      statistics depends on the aspect ratio in a critical, fundamental fashion not
      predicted by theory. The fastest motion was obtained for the wild-type and
      variants that are similar in length. However, shorter and longer cells exhibit
      anomalous, non-Gaussian statistics and nonexponential decay of the
      autocorrelation function, indicating lower collective motility. These results
      suggest that the robust mechanisms to maintain aspect ratios may be important for
      efficient swarming motility. Wild-type cells are optimal in this sense.

PMID- 28452530
TI  - Observation of Genuine Three-Photon Interference.
AB  - Multiparticle quantum interference is critical for our understanding and
      exploitation of quantum information, and for fundamental tests of quantum
      mechanics. A remarkable example of multi-partite correlations is exhibited by the
      Greenberger-Horne-Zeilinger (GHZ) state. In a GHZ state, three particles are
      correlated while no pairwise correlation is found. The manifestation of these
      strong correlations in an interferometric setting has been studied theoretically
      since 1990 but no three-photon GHZ interferometer has been realized
      experimentally. Here we demonstrate three-photon interference that does not
      originate from two-photon or single photon interference. We observe phase
      dependent variation of three-photon coincidences with (92.7+/-4.6)% visibility in
      a generalized Franson interferometer using energy-time entangled photon triplets.
      The demonstration of these strong correlations in an interferometric setting
      provides new avenues for multiphoton interferometry, fundamental tests of quantum
      mechanics, and quantum information applications in higher dimensions.

PMID- 28452531
TI  - Negative-Mass Hydrodynamics in a Spin-Orbit-Coupled Bose-Einstein Condensate.
AB  - A negative effective mass can be realized in quantum systems by engineering the
      dispersion relation. A powerful method is provided by spin-orbit coupling, which
      is currently at the center of intense research efforts. Here we measure an
      expanding spin-orbit coupled Bose-Einstein condensate whose dispersion features a
      region of negative effective mass. We observe a range of dynamical phenomena,
      including the breaking of parity and of Galilean covariance, dynamical
      instabilities, and self-trapping. The experimental findings are reproduced by a
      single-band Gross-Pitaevskii simulation, demonstrating that the emerging features
      shock waves, soliton trains, self-trapping, etc.-originate from a modified
      dispersion. Our work also sheds new light on related phenomena in optical
      lattices, where the underlying periodic structure often complicates their
      interpretation.

PMID- 28452533
TI  - Screening, Hyperuniformity, and Instability in the Sedimentation of Irregular
      Objects.
AB  - We study the overdamped sedimentation of non-Brownian objects of irregular shape
      using fluctuating hydrodynamics. The anisotropic response of the objects to flow,
      caused by their tendency to align with gravity, directly suppresses concentration
      and velocity fluctuations. This allows the suspension to avoid the anomalous
      fluctuations predicted for suspensions of symmetric spheroids. The suppression of
      concentration fluctuations leads to a correlated, hyperuniform structure. For
      certain object shapes, the anisotropic response may act in the opposite
      direction, destabilizing uniform sedimentation.

PMID- 28452535
TI  - Magnetic Field Dependence of Spin Glass Free Energy Barriers.
AB  - We measure the field dependence of spin glass free energy barriers in a thin
      amorphous Ge:Mn film through the time dependence of the magnetization. After the
      correlation length xi(t,T) has reached the film thickness L=155  A so that the
      dynamics are activated, we change the initial magnetic field by deltaH. In
      agreement with the scaling behavior exhibited in a companion Letter [M. Baity
      Jesi et al., Phys. Rev. Lett. 118, 157202 (2017)PRLTAO0031
      900710.1103/PhysRevLett.118.157202], we find that the activation energy is
      increased when deltaH<0. The change is proportional to (deltaH)^{2} with the
      addition of a small (deltaH)^{4} term. The magnitude of the change of the spin
      glass free energy barriers is in near quantitative agreement with the prediction
      of a barrier model.

PMID- 28452536
TI  - Unconventional Topological Phase Transition in Two-Dimensional Systems with Space
      Time Inversion Symmetry.
AB  - We study a topological phase transition between a normal insulator and a quantum
      spin Hall insulator in two-dimensional (2D) systems with time-reversal and
      twofold rotation symmetries. Contrary to the case of ordinary time-reversal
      invariant systems, where a direct transition between two insulators is generally
      predicted, we find that the topological phase transition in systems with an
      additional twofold rotation symmetry is mediated by an emergent stable 2D Weyl
      semimetal phase between two insulators. Here the central role is played by the so
      called space-time inversion symmetry, the combination of time-reversal and
      twofold rotation symmetries, which guarantees the quantization of the Berry phase
      around a 2D Weyl point even in the presence of strong spin-orbit coupling. Pair
      creation and pair annihilation of Weyl points accompanying partner exchange
      between different pairs induces a jump of a 2D Z_{2} topological invariant
      leading to a topological phase transition. According to our theory, the
      topological phase transition in HgTe/CdTe quantum well structure is mediated by a
      stable 2D Weyl semimetal phase because the quantum well, lacking inversion
      symmetry intrinsically, has twofold rotation about the growth direction. Namely,
      the HgTe/CdTe quantum well can show 2D Weyl semimetallic behavior within a small
      but finite interval in the thickness of HgTe layers between a normal insulator
      and a quantum spin Hall insulator. We also propose that few-layer black
      phosphorus under perpendicular electric field is another candidate system to
      observe the unconventional topological phase transition mechanism accompanied by
      the emerging 2D Weyl semimetal phase protected by space-time inversion symmetry.

PMID- 28452537
TI  - Turbulent Kinetic Energy in the Energy Balance of a Solar Flare.
AB  - The energy released in solar flares derives from a reconfiguration of magnetic
      fields to a lower energy state, and is manifested in several forms, including
      bulk kinetic energy of the coronal mass ejection, acceleration of electrons and
      ions, and enhanced thermal energy that is ultimately radiated away across the
      electromagnetic spectrum from optical to x rays. Using an unprecedented set of
      coordinated observations, from a suite of instruments, we here report on a
      hitherto largely overlooked energy component-the kinetic energy associated with
      small-scale turbulent mass motions. We show that the spatial location of, and
      timing of the peak in, turbulent kinetic energy together provide persuasive
      evidence that turbulent energy may play a key role in the transfer of energy in
      solar flares. Although the kinetic energy of turbulent motions accounts, at any
      given time, for only ~(0.5-1)% of the energy released, its relatively rapid (~1
      10  s) energization and dissipation causes the associated throughput of energy
      (i.e., power) to rival that of major components of the released energy in solar
      flares, and thus presumably in other astrophysical acceleration sites.

PMID- 28452538
TI  - Digging Deeper: Observing Primordial Gravitational Waves below the Binary-Black
      Hole-Produced Stochastic Background.
AB  - The merger rate of black hole binaries inferred from the detections in the first
      Advanced LIGO science run implies that a stochastic background produced by a
      cosmological population of mergers will likely mask the primordial gravitational
      wave background. Here we demonstrate that the next generation of ground-based
      detectors, such as the Einstein Telescope and Cosmic Explorer, will be able to
      observe binary black hole mergers throughout the Universe with sufficient
      efficiency that the confusion background can potentially be subtracted to observe
      the primordial background at the level of Omega_{GW}?10^{-13} after 5 years of
      observation.

PMID- 28452539
TI  - Ultrafast Dissociation of Metastable CO^{2+} in a Dimer.
AB  - We triply ionize the van der Waals bound carbon monoxide dimer with intense
      ultrashort pulses and study the breakup channel (CO)_{2}^{3+}
      >C^{+}+O^{+}+CO^{+}. The fragments are recorded in a cold target recoil ion
      momentum spectrometer. We observe a fast CO^{2+} dissociation channel in the
      dimer, which does not exist for the monomer. We found that a nearby charge breaks
      the symmetry of a X^{3}Pi state of CO^{2+} and induces an avoided crossing that
      allows a fast dissociation. Calculation on the full dimer complex shows the
      coupling of different charge states, as predicted from excimer theory, gives rise
      to electronic state components not present in the monomer, thereby enabling fast
      dissociation with higher kinetic energy release. These results demonstrate that
      the electronic structure of molecular cluster complexes can give rise to dynamics
      that is qualitatively different from that observed in the component monomers.

PMID- 28452540
TI  - Probing Microplasticity in Small-Scale FCC Crystals via Dynamic Mechanical
      Analysis.
AB  - In small-scale metallic systems, collective dislocation activity has been
      correlated with size effects in strength and with a steplike plastic response
      under uniaxial compression and tension. Yielding and plastic flow in these
      samples is often accompanied by the emergence of multiple dislocation avalanches.
      Dislocations might be active preyield, but their activity typically cannot be
      discerned because of the inherent instrumental noise in detecting equipment. We
      apply alternate current load perturbations via dynamic mechanical analysis during
      quasistatic uniaxial compression experiments on single crystalline Cu nanopillars
      with diameters of 500 nm and compute dynamic moduli at frequencies 0.1, 0.3, 1,
      and 10 Hz under progressively higher static loads until yielding. By tracking the
      collective aspects of the oscillatory stress-strain-time series in multiple
      samples, we observe an evolving dissipative component of the dislocation network
      response that signifies the transition from elastic behavior to dislocation
      avalanches in the globally preyield regime. We postulate that microplasticity,
      which is associated with the combination of dislocation avalanches and slow
      viscoplastic relaxations, is the cause of the dependency of dynamic modulus on
      the driving rate and the quasistatic stress. We construct a continuum mesoscopic
      dislocation dynamics model to compute the frequency response of stress over
      strain and obtain a consistent agreement with experimental observations. The
      results of our experiments and simulations present a pathway to discern and
      quantify correlated dislocation activity in the preyield regime of deforming
      crystals.

PMID- 28452541
TI  - End Point of the Ultraspinning Instability and Violation of Cosmic Censorship.
AB  - We determine the end point of the axisymmetric ultraspinning instability of
      asymptotically flat Myers-Perry black holes in D=6 spacetime dimensions. In the
      nonlinear regime, this instability gives rise to a sequence of concentric rings
      connected by segments of black membrane on the rotation plane. The latter become
      thinner over time, resulting in the formation of a naked singularity in finite
      asymptotic time and hence a violation of the weak cosmic censorship conjecture in
      asymptotically flat higher-dimensional spaces.

PMID- 28452542
TI  - Impurity Transport in a Mixed-Collisionality Stellarator Plasma.
AB  - A potential threat to the performance of magnetically confined fusion plasmas is
      the problem of impurity accumulation, which causes the concentration of highly
      charged impurity ions to rise uncontrollably in the center of the plasma and
      spoil the energy confinement by excessive radiation. It has long been thought
      that the collisional transport of impurities in stellarators always leads to such
      an accumulation (if the electric field points inwards, which is usually the
      case), whereas tokamaks, being axisymmetric, can benefit from "temperature
      screening," i.e., an outward flux of impurities driven by the temperature
      gradient. Here it is shown, using analytical techniques supported by results from
      a new numerical code, that such screening can arise in stellarator plasmas, too,
      and indeed does so in one of the most relevant operating regimes, where the
      impurities are highly collisional while the bulk plasma is at low collisionality.

PMID- 28452534
TI  - First Demonstration of Electrostatic Damping of Parametric Instability at
      Advanced LIGO.
AB  - Interferometric gravitational wave detectors operate with high optical power in
      their arms in order to achieve high shot-noise limited strain sensitivity. A
      significant limitation to increasing the optical power is the phenomenon of three
      mode parametric instabilities, in which the laser field in the arm cavities is
      scattered into higher-order optical modes by acoustic modes of the cavity
      mirrors. The optical modes can further drive the acoustic modes via radiation
      pressure, potentially producing an exponential buildup. One proposed technique to
      stabilize parametric instability is active damping of acoustic modes. We report
      here the first demonstration of damping a parametrically unstable mode using
      active feedback forces on the cavity mirror. A 15 538 Hz mode that grew
      exponentially with a time constant of 182 sec was damped using electrostatic
      actuation, with a resulting decay time constant of 23 sec. An average control
      force of 0.03 nN was required to maintain the acoustic mode at its minimum
      amplitude.

PMID- 28452543
TI  - Phonoritonic Crystals with a Synthetic Magnetic Field for an Acoustic Diode.
AB  - We develop a rigorous theoretical framework to describe light-sound interaction
      in the laser-pumped periodic multiple-quantum-well structure accounting for
      hybrid phonon-polariton excitations, termed phonoritons. We show that phonoritons
      exhibit the pumping-induced synthetic magnetic field in the artificial
      "coordinate-energy" space that makes transmission of left- and right- going waves
      different. The sound transmission nonreciprocity allows one to use such
      phonoritonic crystals with realistic parameters as optically controlled nanoscale
      acoustic diodes.

PMID- 28452544
TI  - Lattice-Rotation Vortex at the Charged Monoclinic Domain Boundary in a Relaxor
      Ferroelectric Crystal.
AB  - We present evidence of lattice-rotation vortices having an average radius of ~7 
      nm at the ferroelectric domain boundary of (1-x)Pb(Zn_{1/3}Nb_{2/3})O_{3}
      xPbTiO_{3} (x=0.08). Maps of crystal orientations and domain symmetry breaking
      are obtained using scanning convergent beam electron diffraction, which show
      fractional rotation vortices near the 50 degrees  monoclinic domain walls. The
      merging of 2D and 1D topological defects is consistent with inhomogeneous
      boundary charge and expected to have a large impact on the domain-switching
      mechanisms in relaxor ferroelectric crystals and ferroelectric devices.

PMID- 28452545
TI  - Microscopic Phase-Space Exploration Modeling of ^{258}Fm Spontaneous Fission.
AB  - We show that the total kinetic energy (TKE) of nuclei after the spontaneous
      fission of ^{258}Fm can be well reproduced using simple assumptions on the
      quantum collective phase space explored by the nucleus after passing the fission
      barrier. Assuming energy conservation and phase-space exploration according to
      the stochastic mean-field approach, a set of initial densities is generated. Each
      density is then evolved in time using the nuclear time-dependent density
      functional theory with pairing. This approach goes beyond the mean-field theory
      by allowing spontaneous symmetry breaking as well as a wider dynamical phase
      space exploration leading to larger fluctuations in collective space. The total
      kinetic energy and mass distributions are calculated. New information on the
      fission process: fluctuations in scission time, strong correlation between TKE
      and collective deformation, as well as prescission particle emission, are
      obtained. We conclude that fluctuations of the TKE and mass are triggered by
      quantum fluctuations.

PMID- 28452532
TI  - Combined Analysis of Neutrino and Antineutrino Oscillations at T2K.
AB  - T2K reports its first results in the search for CP violation in neutrino
      oscillations using appearance and disappearance channels for neutrino- and
      antineutrino-mode beams. The data include all runs from January 2010 to May 2016
      and comprise 7.482*10^{20} protons on target in neutrino mode, which yielded in
      the far detector 32 e-like and 135  MU-like events, and 7.471*10^{20} protons on
      target in antineutrino mode, which yielded 4 e-like and 66  MU-like events.
      Reactor measurements of sin^{2}2theta_{13} have been used as an additional
      constraint. The one-dimensional confidence interval at 90% for the phase
      delta_{CP} spans the range (-3.13, -0.39) for normal mass ordering. The CP
      conservation hypothesis (delta_{CP}=0, pi) is excluded at 90% C.L.

PMID- 28452546
TI  - Enhancement of Supersymmetry via Renormalization Group Flow and the
      Superconformal Index.
AB  - We find a four-dimensional N=1 gauge theory which flows to the minimal
      interacting N=2 superconformal field theory, the Argyres-Douglas theory, in the
      infrared up to the extra free chiral multiplets. The gauge theory is obtained
      from a certain N=1 preserving deformation of the N=2 SU(2) gauge theory with four
      fundamental hypermultiplets. From this description, we compute the full
      superconformal index and find agreements with the known results in special
      limits.

PMID- 28452547
TI  - Lower Bound on the Energy Density in Classical and Quantum Field Theories.
AB  - A novel method for deriving energy conditions in stable field theories is
      described. In a local classical theory with one spatial dimension, a local energy
      condition always exists. For a relativistic field theory, one obtains the
      dominant energy condition. In a quantum field theory, there instead exists a
      quantum energy condition, i.e., a lower bound on the energy density that depends
      on information-theoretic quantities. Some extensions to higher dimensions are
      briefly discussed.

PMID- 28452548
TI  - Monitoring of the Process of System Information Broadcasting in Time.
AB  - One of the problems of quantum physics is how a measurement turns quantum,
      noncopyable data, towards copyable classical knowledge. We use the quantum state
      discrimination in a central system model to show how its evolution leads to the
      broadcasting of the information, and how orthogonalization and decoherence
      factors allow us to monitor the distance of the state in question to the one
      perfectly broadcasting information, in any moment of time not just
      asymptotically. We illustrate this in the spin-spin model where the distance is
      shown to be typically small and provide the related time scales.

PMID- 28452549
TI  - Reduction of Electron Repulsion and Enhancement of T_{c} in Small Diffusive
      Superconducting Grains.
AB  - The superconducting properties of small metallic grains has been a topic of
      active research for half a century now. Early experiments demonstrated a
      remarkable rise in the critical temperature, T_{c}, with reducing grain size in a
      variety of materials. In two-dimensional diffusive superconductors, T_{c} is
      decreased due to enhanced Coulomb repulsion. We propose that in finite-size
      grains the diffusive enhancement of the Coulomb repulsion is weakened and leads
      ultimately to an increase in T_{c} in isolated, disordered two-dimensional
      grains. Our mechanism is superimposed on the possible enhancement in T_{c} due to
      the change in the density of states of finite-size systems.

PMID- 28452550
TI  - Pumped-Up SU(1,1) Interferometry.
AB  - Although SU(1,1) interferometry achieves Heisenberg-limited sensitivities, it
      suffers from one major drawback: Only those particles outcoupled from the pump
      mode contribute to the phase measurement. Since the number of particles
      outcoupled to these "side modes" is typically small, this limits the
      interferometer's absolute sensitivity. We propose an alternative "pumped-up"
      approach where all the input particles participate in the phase measurement and
      show how this can be implemented in spinor Bose-Einstein condensates and hybrid
      atom-light systems-both of which have experimentally realized SU(1,1)
      interferometry. We demonstrate that pumped-up schemes are capable of surpassing
      the shot-noise limit with respect to the total number of input particles and are
      never worse than conventional SU(1,1) interferometry. Finally, we show that
      pumped-up schemes continue to excel-both absolutely and in comparison to
      conventional SU(1,1) interferometry-in the presence of particle losses, poor
      particle-resolution detection, and noise on the relative phase difference between
      the two side modes. Pumped-up SU(1,1) interferometry therefore pushes the
      advantages of conventional SU(1,1) interferometry into the regime of high
      absolute sensitivity, which is a necessary condition for useful quantum-enhanced
      devices.

PMID- 28452551
TI  - Self-Generated Magnetic Fields in the Stagnation Phase of Indirect-Drive
      Implosions on the National Ignition Facility.
AB  - Three-dimensional extended-magnetohydrodynamic simulations of the stagnation
      phase of inertial confinement fusion implosion experiments at the National
      Ignition Facility are presented, showing self-generated magnetic fields over
      10^{4}  T. Angular high mode-number perturbations develop large magnetic fields,
      but are localized to the cold, dense hot-spot surface, which is hard to
      magnetize. When low-mode perturbations are also present, the magnetic fields are
      injected into the hot core, reaching significant magnetizations, with peak local
      thermal conductivity reductions greater than 90%. However, Righi-Leduc heat
      transport effectively cools the hot spot and lowers the neutron spectra-inferred
      ion temperatures compared to the unmagnetized case. The Nernst effect
      qualitatively changes the results by demagnetizing the hot-spot core, while
      increasing magnetizations at the edge and near regions of large heat loss.

PMID- 28452552
TI  - Dynamically Correcting a CNOT Gate for any Systematic Logical Error.
AB  - We derive a set of composite pulse sequences that generates cnot gates and
      correct all systematic errors within the logical subspace to arbitrary order.
      These sequences are applicable for any two-qubit interaction Hamiltonian and make
      no assumptions about the underlying noise mechanism except that it is constant on
      the time scale of the operation. We do assume access to high-fidelity single
      qubit gates, so single-qubit gate imperfections eventually limit the achievable
      fidelity. However, since single-qubit gates generally have much higher fidelities
      than two-qubit gates in practice, these pulse sequences offer useful dynamical
      correction for a wide range of coupled qubit systems.

PMID- 28452553
TI  - Dynamical and Reversible Control of Topological Spin Textures.
AB  - Recent observations of topological spin textures brought spintronics one step
      closer to new magnetic memories. Nevertheless, the existence of Skyrmions, as
      well as their stabilization, require very specific intrinsic magnetic properties
      which are usually fixed in magnets. Here we address the possibility to
      dynamically control their intrinsic magnetic interactions by varying the strength
      of a high-frequency laser field. It is shown that drastic changes can be induced
      in the antiferromagnetic exchange interactions and the latter can even be
      reversed to become ferromagnetic, provided the direct exchange is already non
      negligible in equilibrium as predicted, for example, in Si doped with C, Sn, or
      Pb adatoms. In the presence of Dzyaloshinskii-Moriya interactions, this enables
      us to tune features of ferromagnetic Skyrmions such as their radius, making them
      easier to stabilize. Alternatively, such topological spin textures can occur in
      frustrated triangular lattices. Then, we demonstrate that a high-frequency laser
      field can induce dynamical frustration in antiferromagnets, where the degree of
      frustration can subsequently be tuned suitably to drive the material toward a
      Skyrmionic phase.

PMID- 28452554
TI  - Frame-Independent Classification of Single-Field Inflationary Models.
AB  - Seemingly unrelated models of inflation that originate from different physical
      setups yield, in some cases, identical predictions for the currently constrained
      inflationary observables. In order to classify the available models, we propose
      to express the slow-roll parameters and the relevant observables in terms of
      frame and reparametrization invariant quantities. The adopted invariant formalism
      makes manifest the redundancy that afflicts the current description of inflation
      dynamics and offers a straightforward way to identify classes of models which
      yield identical phenomenology. In this Letter, we offer a step-to-step recipe to
      recast every single field inflationary model in the proposed formalism, detailing
      also the procedure to compute inflationary observables in terms of frame and
      reparametrization invariant quantities. We hope that our results become the
      cornerstone of a new categorization of viable inflationary models and open the
      way to a deeper understanding of the inflation mechanism.

PMID- 28452555
TI  - Diffractive Focusing of Waves in Time and in Space.
AB  - We study the general wave phenomenon of diffractive focusing from a single slit
      for two types of waves and demonstrate several properties of this effect. Whereas
      in the first situation, the envelope of a surface gravity water wave is modulated
      in time by a rectangular function, leading to temporal focusing, in the second
      example, surface plasmon polariton waves are focused in space by a thin metal
      slit to a transverse width narrower than the slit itself. The observed evolution
      of the phase carrier of the water waves is measured for the first time and
      reveals a nearly flat phase as well as an 80% increase in the intensity at the
      focal point. We then utilize this flat phase with plasmonic beams in the spatial
      domain, and study the case of two successive slits, creating a tighter focusing
      of the waves by putting the second slit at the focal point of the first slit.

PMID- 28452557
TI  - Time-Reversal Symmetry Bounds on the Electromagnetic Response of Asymmetric
      Structures.
AB  - Asymmetric structures support different field distributions and electromagnetic
      responses when excited from different directions. Here we show that time-reversal
      symmetry imposes fundamental constraints on their overall response, beyond those
      dictated by reciprocity. For two-port devices, the asymmetry in field
      distribution for opposite excitations is shown to be fundamentally bounded by the
      reflection at the ports, and the fields are identical everywhere in space in the
      case of full transmission. In multiport and open scenarios, these bounds have
      implications on radiation and scattering at different ports and towards different
      directions. Beyond their theoretical significance, these results provide relevant
      insights into the operation of nonlinear isolators, metasurfaces, and other
      nanophotonic devices.

PMID- 28452556
TI  - Scattering of the Halo Nucleus ^{11}Be on ^{197}Au at Energies around the Coulomb
      Barrier.
AB  - Angular distributions of the elastic, inelastic, and breakup cross sections of
      the halo nucleus ^{11}Be on ^{197}Au were measured at energies below
      (E_{lab}=31.9  MeV) and around (39.6 MeV) the Coulomb barrier. These three
      channels were unambiguously separated for the first time for reactions of ^{11}Be
      on a high-Z target at low energies. The experiment was performed at TRIUMF
      (Vancouver, Canada). The differential cross sections were compared with three
      different calculations: semiclassical, inert-core continuum-coupled-channels and
      continuum-coupled-channels ones with including core deformation. These results
      show conclusively that the elastic and inelastic differential cross sections can
      only be accounted for if core-excited admixtures are taken into account. The
      cross sections for these channels strongly depend on the B(E1) distribution in
      ^{11}Be, and the reaction mechanism is sensitive to the entanglement of core and
      halo degrees of freedom in ^{11}Be.

PMID- 28452558
TI  - Cardiac rehabilitation in cardiac valve surgery patients: Beyond cost
      effectiveness.

PMID- 28452559
TI  - Impact of pro-atrial natriuretic peptide in atrial fibrillation and stroke.

PMID- 28452560
TI  - Effects of a cardiac rehabilitation programme on plasma cardiac biomarkers in
      patients with chronic heart failure.
AB  - Background Cardiac rehabilitation (CR) improves the symptoms, exercise capacity
      and quality of life of chronic heart failure (CHF) patients. Its effects on new
      plasma biomarkers of prognostic importance are unknown. The present study aimed
      at analysing the effects of a structured CR programme on plasma cardiac
      biomarkers in a large population of patients with CHF and reduced left
      ventricular ejection fraction (LVEF). Methods We enrolled 107 consecutive CHF
      patients with LVEF <= 45% in an ambulatory CR programme. Peak VO2 and plasma
      levels of Galectin-3, mid-regional proANP (MR-proADM), soluble suppressor of
      tumorigenicity 2 (sST2) and mid-regional pro-adrenomedullin (MR-proANP) were
      assessed at inclusion and at the end of CR. Twenty-four unenrolled patients were
      managed with standard medical care and evaluated over the same period (no-CR
      group). Results Galectin-3, sST2, MR-proADM and MR-proANP plasma levels decreased
      after CR, with respective median reductions of 6.3% for Galectin 3 ( p < 0.001),
      7.4% for sST2 ( p = 0.036), 6.4% for MR-proADM ( p = 0.001) and 16% for MR-proANP
      ( p < 0.001). MR-proADM was negatively correlated with peak VO2 (rho = -0.529,
      95% confidence interval [CI] -0.654 to -0.375, p < 0.001), and so were their
      relative variations along the course of CR (rho = -0.357, 95% CI -0.518 to 
      0.172, p < 0.001). No change occurred in terms of biomarkers in the no-CR group.
      Conclusions Plasma cardiac biomarkers such as Galectin-3, MR-proADM, sST2 and MR
      proANP all decreased after CR in CHF patients, suggesting an overall improvement
      in the neuro-hormonal profile.

PMID- 28452561
TI  - Follicular growth but absence of oocyte and cumulus maturation during ovarian
      stimulation in the days following surgical abortion: a case report.
AB  - This paper is a case report on the results of an ovarian stimulation performed in
      the days following an induced abortion. A patient had breast cancer diagnosed
      during an early pregnancy. She had an induced abortion and had, before
      chemotherapy an ovarian stimulation, using rFSH and GnRH antagonist, followed by
      follicular puncture for oocyte for vitrification in the view of fertility
      preservation. No oocyte could be obtained despite a good hormonal and
      ultrasonographical follicular growth. This case report suggest that ovarian
      stimulation must be delayed after abortion to allow the maturation of oocyte
      cumulus complexes.

PMID- 28452562
TI  - Risk factors of late cardiogenic shock and mortality in ST-segment elevation
      myocardial infarction patients.
AB  - BACKGROUND: The incidence of cardiogenic shock (CS) in patients with ST-segment
      elevation myocardial infarction (STEMI) is as high as 10%. The majority of
      patients are thought to develop CS after admission (late CS), but the incidence
      in a contemporary STEMI cohort admitted for primary percutaneous intervention
      remains unknown. AIM: The aim of this study was to assess the incidence and time
      of CS onset in patients with suspected STEMI admitted in two high-volume tertiary
      heart centres and to assess the variables associated with the development of late
      CS. METHODS: We included consecutive patients admitted for acute coronary
      angiography with suspected STEMI in a 1-year period. Cardiogenic shock was based
      on clinical criteria and subdivided into patients with shock on admission,
      patients developing shock during catheterisation and patients developing shock
      later during hospitalisation. Follow-up for all-cause mortality was done using
      registries. RESULTS: A total of 2247 patients with suspected STEMI were included,
      whereof 225 (10%) developed CS. The majority (56%) had CS on admission, 16%
      developed CS in the catheterisation laboratory and 28% developed late CS. Thirty
      day mortality was 3.1% versus 47% in non-CS versus CS patients ( plogrank <
      0.0001). Age, stroke, time from symptom onset to intervention, anterior STEMI,
      heart rate/systolic blood pressure ratio and being comatose after resuscitation
      from cardiac arrest were independently associated with the development of late
      CS. CONCLUSION: In this study, 10% of patients admitted with suspected STEMI for
      acute coronary angiography presented with or developed CS. Most were in shock on
      admission. Irrespective of the timing of shock, mortality was high.

PMID- 28452563
TI  - Adaptation and validation of a commercial head phantom for cranial radiosurgery
      dosimetry end-to-end audit.
AB  - OBJECTIVE: To adapt and validate an anthropomorphic head phantom for use in a
      cranial radiosurgery audit. METHODS: Two bespoke inserts were produced for the
      phantom: one for providing the target and organ at risk for delineation and the
      other for performing dose measurements. The inserts were tested to assess their
      positional accuracy. A basic treatment plan dose verification with an ionization
      chamber was performed to establish a baseline accuracy for the phantom and beam
      model. The phantom and inserts were then used to perform dose verification
      measurements of a radiosurgery plan. The dose was measured with alanine pellets,
      EBT extended dose film and a plastic scintillation detector (PSD). RESULTS: Both
      inserts showed reproducible positioning (+/-0.5 mm) and good positional agreement
      between them (+/-0.6 mm). The basic treatment plan measurements showed agreement
      to the treatment planning system (TPS) within 0.5%. Repeated film measurements
      showed consistent gamma passing rates with good agreement to the TPS. For 2%-2 mm
      global gamma, the mean passing rate was 96.7% and the variation in passing rates
      did not exceed 2.1%. The alanine pellets and PSD showed good agreement with the
      TPS (-0.1% and 0.3% dose difference in the target) and good agreement with each
      other (within 1%). CONCLUSION: The adaptations to the phantom showed acceptable
      accuracies. The presence of alanine and PSD do not affect film measurements
      significantly, enabling simultaneous measurements by all three detectors.
      Advances in knowledge: A novel method for thorough end-to-end test of
      radiosurgery, with capability to incorporate all steps of the clinical pathway in
      a time-efficient and reproducible manner, suitable for a national audit.

PMID- 28452564
TI  - Emotional processes in risky and multiattribute health decisions.
AB  - OBJECTIVE: Here, we develop an integrative account of the roles of emotion in
      decision-making. In Part I, we illustrate how emotional inputs into decisions may
      rely on physiological signals from emotions experienced while making the
      decision, and we review evidence suggesting that the failure to represent the
      emotional meaning of options can often reduce decision quality. We propose that
      health-related decrements in the ability to generate emotional reactions lead
      people to inaccurately represent emotional responses and compromise decisions,
      particularly about risk. Part II explores complex decisions in which choice
      options involve trade-offs between positive and negative attributes. We first
      review evidence showing that difficult trade-off decisions generate negative
      affect and physiological arousal. Next, we propose that medical decision-making
      will be linked to short- and long-term stress and health outcomes. CONCLUSION: In
      sum, this article proposes and reviews initial evidence supporting the effective
      use and management of emotional inputs as important to both clinical and non
      clinical populations. Our approach will contribute to the understanding of
      patient-centred emotional decision-making and will inform medical decision aids.

PMID- 28452565
TI  - Administration of Wasabia koreana Ameliorates Irritable Bowel Syndrome-Like
      Symptoms in a Zymosan-Induced Mouse Model.
AB  - Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with
      complex pathophysiology involving the brain-gut axis. To assess the effects of
      Wasabia koreana (WK) on IBS, we employed a mouse model of colonic zymosan
      injection presenting with diarrhea-predominant IBS-like symptoms. Oral WK
      administration significantly diminished stool score, suppressed colon length and
      weight change, and minimized body weight loss without affecting food intake. In
      WK-treated mice, the submucosal thickening and epithelial lining of the colon
      were inhibited and were similar to those of naive mice. Infiltration of mast
      cells into the colon and serum tumor necrosis factor-alpha levels were markedly
      suppressed. These effects were comparable to those of sulfasalazine, an anti
      inflammatory drug. Furthermore, the number of visceral pain-related behaviors was
      significantly decreased, and locomotion activities measured in the elevated plus
      maze and open field tests were significantly increased by WK in a dose-dependent
      manner compared with amitriptyline, an antidepressant. These changes were
      accompanied by reduced FosB2 expression in the brain. Taken together, these data
      suggest that WK may have potential as a medicinal food for IBS by acting on
      inflammatory diarrhea and neural activity.

PMID- 28452566
TI  - Hypothermia after cranial irradiation protects neural progenitor cells in the
      subventricular zone but not in the hippocampus.
AB  - PURPOSE: To explore if hypothermia can reduce the harmful effects of ionizing
      radiation on the neurogenic regions of the brain in young rats. MATERIALS AND
      METHODS: Postnatal day 9 rats were randomized into two treatment groups, hypo-
      and normothermia, or a control group. Treatment groups were placed in chambers
      submerged in temperature-controlled water baths (30  degrees C and 36  degrees C)
      for 8 h, after receiving a single fraction of 8 Gy to the left hemisphere. Seven
      days' post-irradiation, we measured the sizes of the subventricular zone (SVZ)
      and the granule cell layer (GCL) of the hippocampus, and counted the number of
      proliferating (phospho-histone H3+) cells and microglia (Iba1 + cells). RESULTS:
      Irradiation caused a 53% reduction in SVZ size in the normothermia group compared
      to controls, as well as a reduction of proliferating cell numbers by >50%. These
      effects were abrogated in the hypothermia group. Irradiation reduced the number
      of microglia in both treatment groups, but resulted in a lower cell density of
      Iba1 + cells in the SVZs of the hypothermia group. In the GCL, irradiation
      decreased both GCL size and the proliferating cell numbers, but with no
      difference between the treatment groups. The number of microglia in the GCL did
      not change. CONCLUSIONS: Hypothermia immediately after irradiation protects the
      SVZ and its proliferative cell population but the GCL is not protected, one week
      post-irradiation.

PMID- 28452567
TI  - Time, Temperature, and Cationic Dependence of Alkali Activation of Slag: Insights
      from Fourier Transform Infrared Spectroscopy and Spectral Deconvolution.
AB  - The use of waste/by-product materials, such as slag or fly ash, activated using
      alkaline agents to create binding materials for construction applications (in
      lieu of portland cement) is on the rise. The influence of activation parameters
      (SiO2 to Na2O ratio or Ms of the activator, Na2O to slag ratio or n, cation type
      K+ or Na+) on the process and extent of alkali activation of slag under ambient
      and elevated temperature curing, evaluated through spectroscopic techniques, is
      reported in this paper. Fourier transform infrared spectroscopy along with a
      Fourier self-deconvolution method is used. The major spectral band of interest
      lies in the wavenumber range of ~950 cm-1, corresponding to the antisymmetric
      stretching vibration of Si-O-T (T = Si or Al) bonds. The variation in the spectra
      with time from 6 h to 28 days is attributed to the incorporation of Al in the gel
      structure and the enhancement in degree of polymerization of the gel. 29Si
      nuclear magnetic resonance spectroscopy is used to quantify the Al incorporation
      with time, which is found to be higher when Na silicate is used as the activator.
      The Si-O-T bond wavenumbers are also generally lower for the Na silicate
      activated systems.

PMID- 28452568
TI  - Can CT scan protocols used for radiotherapy treatment planning be adjusted to
      optimize image quality and patient dose? A systematic review.
AB  - This article reviews publications related to the use of CT scans for radiotherapy
      treatment planning, specifically the impact of scan protocol changes on CT number
      and treatment planning dosimetry and on CT image quality. A search on PubMed and
      EMBASE and a subsequent review of references yielded 53 relevant articles. CT
      scan parameters significantly affect image quality. Some will also affect
      Hounsfield unit (HU) values, though this is not comprehensively reported on.
      Changes in tube kilovoltage and, on some scanners, field of view and
      reconstruction algorithms have been found to produce notable HU changes. The
      degree of HU change which can be tolerated without changing planning dose by >1%
      depends on the body region and size, planning algorithms, treatment beam energy
      and type of plan. A change in soft-tissue HU value has a greater impact than
      changes in HU for bone and air. The use of anthropomorphic phantoms is
      recommended when assessing HU changes. There is limited published work on CT scan
      protocol optimization in radiotherapy. Publications suggest that HU tolerances of
      +/-20 HU for soft tissue and of +/-50 HU for the lung and bone would restrict
      dose changes in the treatment plan to <1%. Literature related to the use of CT
      images in radiotherapy planning has been reviewed to establish the acceptable
      level of HU change and the impact on image quality of scan protocol adjustment.
      Conclusions have been presented and further work identified.

PMID- 28452569
TI  - Partial alleviation of oxidative stress induced by gamma irradiation in Vigna
      radiata by polyamine treatment.
AB  - PURPOSE: Environmental changes generate free radicals and reactive oxygen species
      (ROS) resulting in abiotic stress in plants. This causes alterations in
      germination, morphology, growth and development ultimately leading to yield loss.
      Gamma irradiation was used to experimentally induce oxidative damage in an
      important pulse crop Vigna radiata (L.) Wilczek or mung bean. Our research was
      aimed towards augmentation of oxidative stress tolerance through treatment with a
      group of aliphatic amines known as polyamines. MATERIALS AND METHODS: We used sub
      lethal doses of gamma irradiation to generate oxidative damage which was
      evaluated using Nitro blue tetrazolium (NBT) staining, total antioxidant
      activity, 1, 1-Diphenyl-2-picryl hydrazyl (DPPH) radical scavenging assay,
      proline content and lipid peroxidation. Changes in internal free polyamines and
      messenger ribonucleic acid (mRNA) expression of key rate-limiting S
      adenosylmethionine decarboxylase (SAMDC) enzyme in polyamine biosynthetic pathway
      was studied using real-time polymerase chain reaction (PCR). RESULTS: We observed
      increased oxidative damage with higher irradiation dose which was partially
      alleviated by putrescine treatment. Internal levels of putrescine and spermidine
      increased with 1 mM (50 and 100 Gy) and 2 mM putrescine treatment. Expression of
      SAMDC also increased with putrescine treatment. CONCLUSION: This study shows that
      treatment with putrescine can partially alleviate oxidative damage caused by
      gamma rays.

PMID- 28452570
TI  - Using intuition or a formal palliative care needs assessment screening process in
      general practice to predict death within 12 months: A randomised controlled
      trial.
AB  - BACKGROUND: Population ageing will lead to more deaths with an uncertain
      trajectory. Identifying patients at risk of dying could facilitate more effective
      care planning. AIM: To determine whether screening for likely death within 12
      months is more effective using screening tools or intuition. DESIGN: Randomised
      controlled trial of screening tools (Surprise Question plus the Supportive and
      Palliative Care Indicators Tool for Surprise Question positive patients) to
      predict those at risk of death at 12 months compared with unguided intuition
      (clinical trials registry: ACTRN12613000266763). SETTING/PARTICIPANTS: Australian
      general practice. A total of 30 general practitioners (screening tool = 12,
      intuition = 18) screened all patients ( n = 4365) aged >=70 years seen at least
      once in the last 2 years. RESULTS: There were 142 deaths (screening tool = 3.1%,
      intuition = 3.3%; p = 0.79). General practitioners identified more at risk of
      dying using Surprise Question (11.8%) than intuition (5.4%; p = 0.01), but no
      difference with Surprise Question positive then Supportive and Palliative Care
      Indicators Tool (5.1%; p = 0.87). Surprise Question positive predicted more
      deaths (53.2%, intuition = 33.7%; p = 0.001), but Surprise Question
      positive/Supportive and Palliative Care Indicators Tool predictions were similar
      (5.1%; p = 0.87 vs intuition). There was no difference in proportions correctly
      predicted to die (Surprise Question = 1.6%, intuition = 1.1%; p = 0.156 and
      Surprise Question positive/Supportive and Palliative Care Indicators Tool = 1.1%;
      p = 0.86 vs intuition). Screening tool had higher sensitivity and lower
      specificity than intuition, but no difference in positive or negative predictive
      value. CONCLUSION: Screening tool was better at predicting actual death than
      intuition, but with a higher false positive rate. Both were similarly effective
      at screening the whole cohort for death. Screening for possible death is not the
      best option for initiating end-of-life planning: recognising increased burden of
      illness might be a better trigger.

PMID- 28452571
TI  - Comparison of diffusion-weighted imaging and enhanced T1-weighted sequencing in
      patients with multiple sclerosis.
AB  - Introduction The purpose of this study was to assess whether demographic, brain
      anatomical regions and contrast enhancement show differences in multiple
      sclerosis (MS) patients with increased diffusion lesions (ID group) compared with
      diffusion restriction (DR group). Method MRI protocol comprised T1- and T2
      weighted sequences with and without gadolinium (Gd), and sagittal three
      dimensional FLAIR sequence, DWI and ADC maps were prospectively performed in 126
      MS patients from January to December 2015. The investigation was conducted to
      evaluate differences in demographic, cord and brain regional, technical, and
      positive or negative Gd contrast imaging parameters in two groups of ID and DR.
      Statistical analysis was performed by using SPSS. Results A total of 9.6% of
      patients showed DR. In the DR group, 66.6% of the patients showed contrast
      enhancement of plaques, whereas 29.2% of the IR group showed enhancement of
      plaques. The most prevalent group was non-enhanced plaques in the ID group,
      followed by Gd-enhanced plaques in the ID group. Patients in the ID group (90.4%)
      were significantly more than in the DR group (9.6%). Out of the 40 patients with
      Gd-enhanced plaques, 80.5% was from the ID group and 19.5% from the DR group.
      Conclusion MRI of the brain, unlike of the cord, with Gd demonstrates significant
      difference in enhancement between the two groups ( p < 0.05). No significant
      difference was seen in demographic, cord and brain regional, and technical
      parameters, EDSS, disease duration, and attack rate as well as demographic and
      regional parameters between the ID and decrease diffusion groups ( p > 0.05).

PMID- 28452572
TI  - Continuing Education- "The Action Level"(r).
AB  - Access "The Action Level"(r) Questions online at:
      http://www.acgih.org/products/joeh/alquestions.htm Access "The Action Level"(r)
      Answers online at: http://www.acgih.org/products/joeh/alanswers.htm Access "The
      Action Level"(r) Registration Form online at:
      https://www.acgih.org/products/joeh/alregfrm.htm "The Action Level,"(r) a self
      study, continuing education program, provides a convenient and interesting
      opportunity for individuals to expand their knowledge in relevant areas of
      industrial hygiene, as well as occupational and environmental safety and health.
      The program is approved by both the American Board of Industrial Hygiene, and the
      Board of Certified Safety Professionals, which award Certification Maintenance
      (CM) points and Continuance of Certification (COC) points, respectively, for
      successful participation. Participants must read each issue of the Journal,
      answer "The Action Level"(r) questions, and return the completed answer sheet at
      the end of that issue's "The Action Level"(r) column. To earn the designated CM
      or COC credit, a score of 70 percent or better is required within a 12-month
      period. Certified Industrial Hygienists and Certified Associate Industrial
      Hygienists may earn 2 points per year. Certified Safety Professionals may earn
      1.2 points per year. Enrollment is possible each month, but points are awarded
      only four times each year-in March, June, September, and December-to participants
      who score an average of 70 percent or better within each threemonth period. For
      example, if you register in December 2004, you will receive 0.5 CM points and/or
      0.3 COC points for your January, February, and March 2005 responses (assuming
      that you submitted all answer sheets and scored a 70 percent or better average on
      them; only in your first quarter of enrollment will you be permitted to submit
      answer sheets for two months and receive full credit; three answer sheets are
      required for all other quarters). Further, you'll receive 0.5 CM points or 0.3
      COC points after satisfactorily completing the April, May, and June 2005 issues,
      and so on. To enroll, complete the registration form and the answer sheet at the
      end of this "The Action Level"(r) column. The cost is $179 (ACGIH(r)/AIHA
      members)/$199 (nonmembers) for one year. Nonmembers are encouraged to become
      members to take advantage of the 10-percent member discount. For more information
      regarding ACGIH(r) membership, call 513-742-2020, or apply online at
      http://www.acgih.org/members/memberform.htm . Checks must be in U.S. currency,
      drawn on a U.S. bank, and payable to ACGIH(r). We also accept AmEx, MasterCard,
      Discover, and Visa. This continuing education program fee is separate from the
      Journal subscription cost. The fee covers administration costs, and is
      nonrefundable. Submissions must be received by the date listed on each answer
      sheet.

PMID- 28452573
TI  - Bullying and Being Bullied in Childhood Are Associated With Different
      Psychosocial Risk Factors for Poor Physical Health in Men.
AB  - Bullying and being bullied in childhood are both linked with later adjustment
      problems. The impact of childhood bullying on risk for poor physical health in
      adulthood is understudied. Black and White men ( n = 305; mean age = 32.3 years)
      enrolled in the Pittsburgh Youth Study since the first grade underwent a
      comprehensive assessment of psychosocial, behavioral, and biological risk factors
      for poor health. Indices of bullying and being bullied were created by averaging
      annual ratings collected from participants and their caregivers when the
      participants were 10 to 12 years old. Results showed that being a bully in
      childhood was associated with greater stress and aggression and poorer health
      behaviors in adulthood, whereas being a victim of bullies in childhood was
      associated with lower socioeconomic resources, less optimism, and greater unfair
      treatment in adulthood. Unexpectedly, neither bullying nor being bullied in
      childhood was related to inflammation or metabolic syndrome. Bullying and being
      bullied in childhood were associated with distinct domains of psychosocial risk
      in adulthood that may later lead to poor physical health.

PMID- 28452574
TI  - Water transport through the intestinal epithelial barrier under different osmotic
      conditions is dependent on LI-cadherin trans-interaction.
AB  - In the intestine water has to be reabsorbed from the chymus across the intestinal
      epithelium. The osmolarity within the lumen is subjected to high variations
      meaning that water transport often has to take place against osmotic gradients.
      It has been hypothesized that LI-cadherin is important in this process by keeping
      the intercellular cleft narrow facilitating the buildup of an osmotic gradient
      allowing water reabsorption. LI-cadherin is exceptional among the cadherin
      superfamily with respect to its localization along the lateral plasma membrane of
      epithelial cells being excluded from adherens junction. Furthermore it has 7 but
      not 5 extracellular cadherin repeats (EC1-EC7) and a small cytosolic domain. In
      this study we identified the peptide VAALD as an inhibitor of LI-cadherin trans
      interaction by modeling the structure of LI-cadherin and comparison with the
      known adhesive interfaces of E-cadherin. This inhibitory peptide was used to
      measure LI-cadherin dependency of water transport through a monolayer of
      epithelial CACO2 cells under various osmotic conditions. If LI-cadherin trans
      interaction was inhibited by use of the peptide, water transport from the luminal
      to the basolateral side was impaired and even reversed in the case of hypertonic
      conditions whereas no effect could be observed at isotonic conditions. These data
      are in line with a recently published model predicting LI-cadherin to keep the
      width of the lateral intercellular cleft small. In this narrow cleft a high
      osmolarity can be achieved due to ion pumps yielding a standing osmotic gradient
      allowing water absorption from the gut even if the faeces is highly hypertonic.

PMID- 28452575
TI  - Paracellular transport as a strategy for energy conservation by multicellular
      organisms?
AB  - Paracellular transport of solutes and water accompanies transcellular transport
      across epithelial barriers and together they serve to maintain internal body
      composition. However, whether paracellular transport is necessary and why it
      evolved is unknown. In this commentary I discuss our recent studies to address
      this question in the proximal tubule of the kidney. Paracellular reabsorption of
      sodium occurs in the proximal tubule and is mediated by claudin-2. However,
      deletion of claudin-2 in mice does not affect whole kidney sodium excretion
      because it can be completely compensated by downtream transcellular transport
      mechanisms. This occurs at the expense of increased oxygen consumption, tissue
      hypoxia and increased susceptibility to ischemic injury. It is concluded that
      paracellular transport acts as an energy saving mechanism to increase transport
      without consuming additional oxygen. It is speculated that this might be why
      paracellular transport evolved in leaky epithelia with high transport needs.

PMID- 28452576
TI  - The effects of a common stainless steel orthodontic bracket on the diagnostic
      quality of cranial and cervical 3T- MR images: a prospective, case-control study.
AB  - OBJECTIVES: To evaluate the effect of orthodontic stainless steel brackets and
      two different types of archwires on the diagnostic quality of 3-T MR images.
      METHODS: This prospective, case-control study was conducted following
      Strengthening the Reporting of Observational Studies in Epidemiology guidelines.
      The recruitment was conducted among orthodontic patients. 80 subjects, requiring
      MRI for the presence of temporomandibular disorders, were enrolled and divided
      into four groups: 20 patients using aligners (control group); 20 patients with
      stainless steel brackets without archwires; 20 patients with stainless steel
      brackets and nickel-titanium archwires; and 20 patients with stainless steel
      brackets and stainless steel archwires. Two experts in neuroradiology evaluated
      the images to determine the amount of distortion in 6 regions and 48 districts. A
      score was subjectively assigned according to a modified receiver operating
      characteristic method of distortion classification. Any disagreement was resolved
      through consensus seeking; when this was not possible, a third neuroradiologist
      was consulted. The following statistical methods were used: descriptive
      statistics, Cohen's kappa coefficient (k), Kruskal-Wallis test, pairwise
      comparisons using the Dunn-Bonferroni approach. The significance was set at p <=
      0.05. RESULTS: The presence of stainless steel brackets with or without archwires
      negatively influenced MRI of the cervical region, paranasal sinuses, head and
      neck region, and cervical vertebrae but did not influence MRI of brain and
      temporomandibular joint regions. CONCLUSIONS: Patients with a stainless steel
      multibracket orthodontic appliance should remove it before cervical vertebrae,
      cervical region, paranasal sinuses, and head and neck MRI scans. The brain and
      temporomandibular joint region MRI should not require the removal of such
      appliances.

PMID- 28452577
TI  - Novel, nano-sized, liposome-encapsulated polyamidoamine dendrimer derivatives
      facilitate tumour targeting by overcoming the polyethylene glycol dilemma and
      integrin saturation obstacle.
AB  - Drug delivery systems (DDSs) commonly employ arginine-glycine-aspartic acid (RGD)
      peptides with polyethylene glycol (PEG)-dependent enhanced permeability and
      retention (EPR) effect to optimise tumour-targeting. However, the PEG dilemma and
      integrin saturation obstacle are major challenges. To address these issues, we
      constructed a novel, nano-sized DDS by encapsulating doxorubicin (DOX)-loaded
      folic acid derivatives of polyamidoamine dendrimer (PAMAM G5.0) in cyclic RGD
      tyrosine-lysine pentapeptide (c[RGDyK])-modified liposomes (RGD-SL[FND/DOX]),
      prepared using thin-film hydration, film-dispersion and hydration-sonication. The
      liposomes were PEGylated, sterically stabilised and pH-sensitive. In vitro, RGD
      SL[FND/DOX] showed pH-sensitive holistic FND/DOX release, and pH-dependent uptake
      and cytotoxicity in human cancer KB cells. At pH 7.4, RGD-SL[FND/DOX]
      demonstrated greater cellular uptake and cytotoxicity than relevant control
      formulations (except FND/DOX) did, although this advantage disappeared at pH 6.5.
      In vivo, RGD-SL[FND/DOX] inhibited S180 sarcoma xenografted tumour growth in
      Kunming mice more effectively than FND/DOX did. These findings demonstrate the
      feasibility of constructing double-stage tumour-targeting nano-sized DDSs such as
      RGD-SL[FND/DOX]. c[RGDyK] and the EPR effect, facilitated by the particle size
      (about 110 nm) and PEGylation, helped to target the DDS to the tumour tissue,
      while the subsequent pH-dependent release of FND/DOX and folic acid-mediated
      endocytosis specifically targeted the tumour cells, thereby overcoming the PEG
      dilemma and integrin saturation obstacle.

PMID- 28452578
TI  - Functional and Quality of Life Outcomes of a Hand Surgery Mission to Honduras.
AB  - BACKGROUND: The objective of this study was to assess functional, quality of
      life, and satisfaction outcomes of a hand surgery short-term surgical mission
      (STSM) to Honduras, and determine whether patient demographics and surgery
      characteristics during a surgical mission correlate with outcome. METHODS: A
      total of 63 patients who received upper extremity surgery at a week-long hand
      surgery STSM to Honduras in March 2013 participated in the study. A before-after
      study design was used. Before receiving surgery, participants completed the Quick
      Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire and the
      Short Form 12 Health Survey version 2 (SF12v2). Four months postoperatively,
      participants completed the QuickDASH, SF12v2, and Satisfaction Survey. RESULTS:
      The mean QuickDASH score significantly improved preoperatively to
      postoperatively. Demographics measures of age, sex, education, and income did not
      correlate with QuickDASH scores. Preoperative QuickDASH statistically
      significantly correlated with surgery type: Carpal tunnel patients had the
      highest scores (worst functioning). Postoperatively, mass excision and scar
      contracture/skin graft patients were correlated with the lowest scores. Carpal
      tunnel and tendon surgery patients showed greatest correlation with QuickDASH
      improvement. SF-12 scores revealed improvements in mental domains and declines in
      physical domains. CONCLUSIONS: Hand surgery performed during STSMs can result in
      significant functional improvement, regardless of socioeconomic status. Patients
      benefited from both simpler and more complex operations. Four months after
      surgery, general health-related quality of life measures showed improved mental
      indices. Measured physical indices declined despite improved QuickDASH scores.
      This may be due to the early general postoperative state. Further outcome
      research in STSMs in additional countries and specialties is required to expand
      our conclusions to other STSM contexts and guide best practices in STSMs.

PMID- 28452582
TI  - Introduction to the Special Issue on the Development of People With Down Syndrome
      Throughout the Lifespan (Part 1).

PMID- 28452581
TI  - The Arizona Cognitive Test Battery for Down Syndrome: Test-Retest Reliability and
      Practice Effects.
AB  - A multisite study investigated the test-retest reliability and practice effects
      of a battery of assessments to measure neurocognitive function in individuals
      with Down syndrome (DS). The study aimed to establish the appropriateness of
      these measures as potential endpoints for clinical trials. Neurocognitive tasks
      and parent report measures comprising the Arizona Cognitive Test Battery (ACTB)
      were administered to 54 young participants with DS (7-20 years of age) with mild
      to moderate levels of intellectual disability in an initial baseline evaluation
      and a follow-up assessment 3 months later. Although revisions to ACTB measures
      are indicated, results demonstrate adequate levels of reliability and resistance
      to practice effects for some measures. The ACTB offers viable options for
      repeated testing of memory, motor planning, behavioral regulation, and attention.
      Alternative measures of executive functioning are required.

PMID- 28452583
TI  - Associations of Child and Adolescent Mastery Motivation and Self-Regulation With
      Adult Outcomes: A Longitudinal Study of Individuals With Down Syndrome.
AB  - This 20-year prospective longitudinal study focuses on the contribution of
      mastery motivation and self-regulation to adult outcomes for individuals with
      Down syndrome. In earlier phases of the research, 25 participants completed
      measures of cognitive ability, mastery motivation and self-regulation in
      childhood (4 to 6 years) and adolescence (11 to 15 years). In the adult phase
      reported here, self-determination and adaptive behavior were assessed in 21 of
      the original participants at age 23 to 26 years. Mastery motivation and self
      regulation made unique contributions to adult outcomes, over and above the
      effects of cognitive ability. The findings provide powerful evidence about the
      important role of child and adolescent mastery motivation and self-regulation for
      the adult lives of individuals with Down syndrome.

PMID- 28452585
TI  - Functionally enhanced brown adipose tissue in Ames dwarf mice.
AB  - Reduced insulin-like growth factor 1/insulin signaling (IIS) has been linked to
      extended longevity in species ranging from yeast to mammals. In mammals, this is
      exemplified in Ames dwarf (Prop1df/df) mice, which have a 40%-60% increase in
      longevity (males and females, respectively) due to their recessive Prop1 loss-of
      function mutation that results in lack of growth hormone (GH), thyroid
      stimulating hormone and prolactin. Our laboratory has previously shown that Ames
      dwarf mice have functionally unique white adipose tissue (WAT) that improves,
      rather than impairs, insulin sensitivity. Because GH and thyroid hormone are
      integral to adipose tissue development and function, we hypothesized that brown
      adipose tissue (BAT) in Ames dwarf mice may also be functionally unique and/or
      enhanced. Here, we elaborate on our recent findings, which demonstrate that BAT
      is functionally enhanced in Ames dwarf mice, and suggest that BAT removal in
      these mice results in utilization of WAT depots as an energy source. We also
      discuss how our findings compare to those in other long-lived dwarf mice with
      altered IIS, which unlike Ames dwarf mice, are essentially euthyroid. Lastly, we
      provide some insights into the implications of these findings and discuss some of
      the necessary future work in this area.

PMID- 28452584
TI  - Outcome Measures for Clinical Trials in Down Syndrome.
AB  - Increasingly individuals with intellectual and developmental disabilities,
      including Down syndrome, are being targeted for clinical trials. However, a
      challenge exists in effectively evaluating the outcomes of these new
      pharmacological interventions. Few empirically evaluated, psychometrically sound
      outcome measures appropriate for use in clinical trials with individuals with
      Down syndrome have been identified. To address this challenge, the National
      Institutes of Health (NIH) assembled leading clinicians and scientists to review
      existing measures and identify those that currently are appropriate for trials;
      those that may be appropriate after expansion of age range addition of easier
      items, and/or downward extension of psychometric norms; and areas where new
      measures need to be developed. This article focuses on measures in the areas of
      cognition and behavior.

PMID- 28452586
TI  - Stress turns on the heat: Regulation of mitochondrial biogenesis and UCP1 by ROS
      in adipocytes.
AB  - Reactive oxygen species (ROS) production and oxidative stress (OS) in adipose
      tissue are associated with obesity and insulin resistance (IR). The nature of
      this relationship i.e., cause and effect or consequence has not been clearly
      determined. We provide evidence that elevated mitochondrial ROS generated by
      adipocytes from mice with diet-induced obesity (DIO) represents an adaptive
      mechanism that precipitates fatty acid oxidation, mitochondrial biogenesis, and
      mitochondrial uncoupling in an effort to defend against weight gain. Consistent
      with that, mice with adipocyte-specific deletion of manganese superoxide
      dismutase (MnSOD) exhibit increased adipocyte superoxide generation and are
      protected from weight gain and insulin resistance which otherwise develops in
      wild-type (WT) mice that consume an obesogenic diet. The defense mechanism
      displayed by MnSOD-deficiency in fat cells appears to be mediated by a dual
      effect of ROS on inefficient substrate oxidation through uncoupling of oxidative
      phosphorylation and enhanced mitochondrial biogenesis. The aim of this commentary
      is to summarize and contextualize additional evidence supporting the importance
      of mitochondrial ROS in the regulation of mitochondrial biogenesis and the
      modulation of uncoupling protein 1 (UCP1) expression and activation in both white
      and brown adipocytes.

PMID- 28452587
TI  - Fasting rapidly increases fatty acid oxidation in white adipose tissue of young
      broiler chickens.
AB  - Upregulating the fatty acid oxidation capacity of white adipose tissue in mice
      protects against diet-induced obesity, inflammation and insulin resistance. Part
      of this capacity results from induction of brown-like adipocytes within classical
      white depots, making it difficult to determine the oxidative contribution of the
      more abundant white adipocytes. Avian genomes lack a gene for uncoupling protein
      1 and are devoid of brown adipose cells, making them a useful model in which to
      study white adipocyte metabolism in vivo. We recently reported that a brief (5
      hour) period of fasting significantly upregulated many genes involved in
      mitochondrial and peroxisomal fatty acid oxidation pathways in white adipose
      tissue of young broiler chickens. The objective of this study was to determine if
      the effects on gene expression manifested in increased rates of fatty acid
      oxidation. Abdominal adipose tissue was collected from 21 day-old broiler chicks
      that were fasted for 3, 5 or 7 hours or fed ad libitum (controls). Fatty acid
      oxidation was determined by measuring and summing 14CO2 production and 14C
      labeled acid-soluble metabolites from the oxidation of [1-14C] palmitic acid.
      Fasting induced a progressive increase in complete fatty acid oxidation and
      citrate synthase activity relative to controls. These results confirm that fatty
      acid oxidation in white adipose tissue is dynamically controlled by nutritional
      status. Identifying the underlying mechanism may provide new therapeutic targets
      through which to increase fatty acid oxidation in situ and protect against the
      detrimental effects of excess free fatty acids on adipocyte insulin sensitivity.

PMID- 28452590
TI  - Habitual physical activity protects against lipopolysaccharide-induced
      inflammation in mouse adipose tissue.
AB  - Sepsis is a systemic inflammatory response to infection, with no preventative
      strategies. In this study, we identify a role for habitual physical activity in
      the prevention of adipose tissue inflammation induced by a model of sepsis,
      lipopolysaccharide (LPS). Male C57BL/6J mice (8 weeks old) were housed with
      access to voluntary wheel running (VWR) or sedentary (SED) for 10 weeks. Mice
      were then injected with LPS (2 mg/kg) or saline (SAL), and tissues were removed 6
      hours post-injection. VWR attenuated body, epididymal adipose tissue (eWAT), and
      subcutaneous inguinal adipose tissue (iWAT) mass gain, improved glucose
      tolerance, increased markers of mitochondrial biogenesis in iWAT and eWAT, and
      increased UCP-1 protein content in iWAT. In iWAT, VWR attenuated the LPS induced
      increase in mRNA expression of TNF-alpha, MCP-1, and follistatin, along with
      phosphorylation of STAT3. In addition, VWR had a main effect for reducing iWAT
      mRNA expression of IL-1beta, IL-6, and SOCS3. In eWAT, VWR had a main effect for
      reducing mRNA expression of IL-1beta, MCP-1, IL-6, and follistatin. Further, VWR
      increased SOCS3 mRNA expression and phosphorylation of STAT3 in SAL mice, thus
      the relative change in response to LPS for these markers was attenuated. The
      protective effect of prior physical activity occurred in conjunction with
      increases in the protein content of a component of the LPS binding complex,
      MyD88. Overall, the results from this study demonstrate that habitual physical
      activity can attenuate the LPS induced inflammatory response in adipose tissue
      and this occurs to a greater extent in iWAT compare with eWAT.

PMID- 28452589
TI  - Lysyl oxidase propeptide promotes adipogenesis through inhibition of FGF-2
      signaling.
AB  - Lysyl oxidase (LOX) catalyzes the oxidative deamination of lysine residues in
      collagen and elastin, key components of connective tissue. LOX is synthesized as
      an inactive 50 kD pre-proenzyme, and secreted to the extracellular matrix where
      it is cleaved into an active 32 kD LOX, and an 18kD free propeptide (LOX-PP),
      purportedly an inhibitor of fibroblast growth factor-2 (FGF-2) signaling. Given
      that adipocytes are distributed inside the connective tissue, it is likely that
      LOX-PP has an important regulatory role in adipogenesis, which has not been
      studied. Using NIH 3T3-L1 cells, we observed that FGF-2 inhibited adipogenesis,
      and LOX-PP promoted adipogenesis of 3T3-L1 cells in the presence of FGF-2; the
      expression of peroxisome proliferator-activated receptor (PPAR) gamma and CCAAT
      enhancer binding protein (C/EBP) alpha, two markers of adipogenesis, were
      enhanced in the presence of LOX-PP. We further observed that LOX-PP down
      regulated AKT and ERK1/2, two proliferative signaling proteins down-stream of FGF
      2 signaling. Similarly, inhibition of FGF-2 receptor signaling by canofin, a
      competitive inhibitor of FGF-2 receptor, promoted adipogenesis albeit less
      effective compared to LOX-PP. To further explore whether LOX-PP promoted
      adipogenesis through inhibition of FGF-2 signaling, site directed mutagenesis of
      LOX-PP, resulting in an Arg158 to Gln158 mutation which abolishes the inhibitory
      activity of LOX-PP to FGF-2 receptor, attenuated the adipogenic promoting
      properties of LOX-PP. In summary, for the first time, our data show that LOX-PP
      enhances adipogenesis at least partially through inhibition of FGF-2 receptor
      signaling. Our data suggest that LOX-PP may serve as a bona fide therapeutic
      target for regulating adipogenesis and adipose tissue development.

PMID- 28452591
TI  - Donor-dependent variances of human adipose-derived stem cells in respect to the
      in-vitro endothelial cell differentiation capability.
AB  - Human adipose-derived stem cells (ASC) have been shown to differentiate into
      mature adipocytes and to play an important role in creating the vasculature,
      necessary for white adipose tissue to function. To study the stimulatory capacity
      of ASC on endothelial progenitor cells we used a commercially available co
      culture system (V2a - assay). ASC, isolated from lipoaspirates of 18 healthy
      patients, were co-cultured for 13 d on endothelial progenitor cells. Using anti
      CD31 immunostaining, cells that had undergone endothelial differentiation were
      quantified after the defined co-cultivation period. Endothelial cell
      differentiation was observed and demonstrated by an increase in area covered by
      CD31+ cells compared with less to no endothelial cell differentiation in negative
      and media-only controls. Enzyme-linked immunosorbent assay (ELISA) for vascular
      endothelial growth factor (VEGF) in supernatant medium collected during the co
      cultivation period revealed elevated VEGF levels in the co-culture samples as
      compared with ASC cultures alone, whereas no increase in adiponectin was detected
      by ELISA. These findings help to provide further insights in the complex
      interplay of adipose derived cells and endothelial cells and to better understand
      the diversity of ASCs in respect of their stimulatory capacity to promote
      angiogenesis in vitro.

PMID- 28452593
TI  - The relationship between geographical and social space and approaches to care
      among rural and urban caregivers caring for a family member with Dementia: a
      qualitative study.
AB  - Knowledge about family caregivers in rural areas remains sparse. No studies to
      date have addressed the sociocultural aspects in caregiving, thus neglecting
      potentially significant data. This study aimed to explore and better understand
      family caregivers' experiences in rural and urban areas and the sociocultural
      spheres that these two areas represent. How do family caregivers approach their
      caregiving situation? A hermeneutical approach was chosen to uncover the
      underlying meanings of experiences. Open-ended in-depth interviews were
      conducted. The ontological and epistemological roots are based on hermeneutic
      philosophy, where a human being's existence is viewed as socially constructed.
      The study followed a purposeful sampling. Semi-structured in-depth interviews
      were conducted with 12 rural and 11 urban family caregivers to persons with
      dementia. These were then analyzed in accordance with the hermeneutical process.
      The findings provide insight into the variations of family caregiver approaches
      to caregiving in rural and urban areas of Sweden. There seemed to be a prevalence
      of a more accepting and maintaining approach in the rural areas as compared to
      the urban areas, where caregiving was more often viewed as an obligation and
      something that limited one's space. Differences in the construction of family
      identity seemed to influence the participants approach to family caregiving.
      Therefore, community-based caregiving for the elderly needs to become aware of
      how living within a family differs and how this affects their views on being a
      caregiver. Thus, support systems must be individually adjusted to each family's
      lifestyles so that this is more in tune with their everyday lives.

PMID- 28452592
TI  - A cellular model for the investigation of depot specific human adipocyte biology.
AB  - Upper-body adiposity is associated with increased metabolic disease risk, while
      lower-body adiposity is paradoxically protective. Efforts to understand the
      underlying mechanisms require appropriate and reproducible in vitro culture
      models. We have therefore generated immortalised (im) human preadipocyte (PAD)
      cell lines derived from paired subcutaneous abdominal and gluteal adipose tissue.
      These cell lines, denoted imAPAD and imGPAD display enhanced proliferation and
      robust adipogenic capacities. Differentiated imAPAD and imGPAD adipocytes
      synthesize triglycerides de novo and respond lipolytically to catecholamine
      stimulation. Importantly the cells retain their depot-of-origin 'memory' as
      reflected by inherent differences in fatty acid metabolism and expression of
      depot-specific developmental genes. These features make these cell lines an
      invaluable tool for the in vitro investigation of depot-specific human adipocyte
      biology.

PMID- 28452595
TI  - Erratum.

PMID- 28452594
TI  - Zellweger syndrome: Depiction of MRI findings in early infancy at 3.0 Tesla.
AB  - Zellweger syndrome, also referred to as cerebrohepatorenal syndrome, is a rare
      autosomal recessive disease representing the most severe form of the peroxisomal
      biogenesis disorders. Neuroanatomical sequelae include impaired neuronal
      migration, diffuse hypomyelination, and sensorineural degeneration. Due to the
      rare and severe nature of this disorder, early mortality, and comorbidities that
      place the patient at risk for sedated imaging, high-resolution magnetic resonance
      imaging findings of Zellweger syndrome are scarce in the literature. Presented
      here is a case of this rare disease imaged at 3.0 Tesla.

PMID- 28452596
TI  - Assessment Trends Among Neuropsychologists Conducting Sport-Related Concussion
      Evaluations.
AB  - Neuropsychologists regularly conduct sport-related concussion (SRC) evaluations,
      although research has not tracked these assessment practices. As part of a survey
      of neuropsychological test usage, we analyzed data from 215 neuropsychologists
      who conduct SRC evaluations. Only 15% reported conducting baseline assessments of
      athletes as part of a sports program and 92% evaluate athletes' post-concussion
      without baseline data. The majority of respondents use a full battery, considered
      the most reliable approach for assessing concussion symptoms in athletes. Only 6%
      use computerized tests exclusively (>50% ImPACT). We discuss the implications of
      these results and address challenges faced by neuropsychologists who perform SRC
      evaluations.

PMID- 28452597
TI  - Neural Correlates of Choking Under Pressure: Athletes High in Sports Anxiety
      Monitor Errors More When Performance Is Being Evaluated.
AB  - We investigated the relationship between performance-related anxiety and the
      neural response to errors. Using the sport anxiety scale, we selected university
      athletes high in sports anxiety and low in sports anxiety. The two groups
      performed a spatial Stroop task while their performance was being evaluated by an
      experimenter and also during a control (i.e., no evaluation) condition. The error
      related negativity was significantly larger during the evaluation than control
      condition among athletes who reported high performance-related anxiety. These
      results suggest that performance evaluation may make errors particularly aversive
      or salient for individuals who fail to perform well under pressure.

PMID- 28452598
TI  - Cortical Structures Associated With Sports Participation in Children: A
      Population-Based Study.
AB  - We studied cortical morphology in relation to sports participation and type of
      sport using a large sample of healthy children (n = 911). Sports participation
      data was collected through a parent-reported questionnaire. Magnetic resonance
      scans were acquired, and different morphological brain features were quantified.
      Global volumetric measures were not associated with sports participation. We
      observed thicker cortex in motor and premotor areas associated with sports
      participation. In boys, team sports participation, relative to individual sports,
      was related to thinner cortex in prefrontal brain areas involved in the
      regulation of behaviors. This study showed a relationship between sports
      participation and brain maturation.

PMID- 28452599
TI  - The Neuropsychology of Sport and Performance.

PMID- 28452600
TI  - Comparison of Neurocognitive Performance in Contact and Noncontact Nonconcussed
      High School Athletes Across a Two-Year Interval.
AB  - Investigating short-term effects of subconcussive impacts on neurocognitive
      functioning, we employed a repeated measures multivariate model and regression
      based measure to examine neurocognitive changes in 771 contact and noncontact
      high school athletes over a two-year period. Results reveal significant changes
      in Visual Motor Speed for both groups over a two-year period, with small effect
      sizes. According to regression-based measures, differences in contact sport
      athletes' expected Time 2 performances were significant for Visual Motor Speed,
      also with minimal effects. Results do not conclusively implicate subconcussive
      hits as the offending factor in differences observed, with gender and sport-type
      possibly contributing to the small effects.

PMID- 28452601
TI  - Updating the Rey Dot Counting Test for Use in Collegiate Baseline Concussion
      Testing.
AB  - Athletes occasionally attempt to lower their baseline scores to mask the effects
      of a concussion during post-trauma assessment, a phenomenon known as sandbagging.
      In order to help prevent this from occurring, the Rey Dot Counting Test (DCT) was
      examined as a potential measure to be added to a Division II university screening
      battery. Investigators utilized samples of athletes at baseline and non-athlete
      students instructed to provide honest effort or suppressed effort, either naively
      or coached. The results support the use of the DCT as a valid measure of
      suboptimal performance when using modified norms established from collegiate
      populations.

PMID- 28452602
TI  - Effect of Enzogenol(r) Supplementation on Cognitive, Executive, and
      Vestibular/Balance Functioning in Chronic Phase of Concussion.
AB  - This study examined the feasibility of Enzogenol(r) as a potential treatment
      modality for concussed individuals with residual symptoms in the chronic phase.
      Forty-two student-athletes with history of sport-related concussion were
      enrolled, comparing Enzogenol(r) versus placebo. Testing was conducted using
      virtual reality (VR) and electroencephalography (EEG), with neuropsychological
      (NP) tasks primarily used to induce cognitive challenges. After six weeks, the
      Enzogenol(r) group showed enhanced frontal-midline theta, and decreased parietal
      theta power, indicating reduced mental fatigue. Subjects enrolled in the
      Enzogenol(r) group also self-reported reduced mental fatigue and sleep problems.
      This suggests that Enzogenol(r) has the potential to improve brain functioning in
      the chronic phase of concussion.

PMID- 28452603
TI  - Effects of music therapy under general anesthesia in patients undergoing
      abdominal surgery.
AB  - BACKGROUND: Music therapy, an innovative approach that has proven effectiveness
      in many medical conditions, seems beneficial also in managing surgical patients.
      The aim of this study is to evaluate its effects, under general anesthesia, on
      perioperative patient satisfaction, stress, pain, and awareness. METHODS: This is
      a prospective, randomized, double-blind study conducted in the operating theatre
      of visceral surgery at Sahloul Teaching Hospital over a period of 4 months.
      Patients aged more than 18 undergoing a scheduled surgery under general
      anesthesia were included. Patients undergoing urgent surgery or presenting
      hearing or cognitive disorders were excluded. Before induction, patients wore
      headphones linked to an MP3 player. They were randomly allocated into 2 groups:
      Group M (with music during surgery) and group C (without music). Hemodynamic
      parameters, quality of arousal, pain experienced, patient's satisfaction, and
      awareness incidence during anesthesia were recorded. RESULTS: One hundred and
      forty patients were included and allocated into 2 groups that were comparable in
      demographic characteristics, surgical intervention type and anesthesia duration.
      Comparison of these two groups regarding the hemodynamic profile found more
      stability in group M for systolic arterial blood pressure. A calm recovery was
      more often noted in group M (77.1% versus 44%, p < 10-3). The average Visual
      Analog Scale (VAS) score was lower in the intervention group (33.8 +/- 13.63
      versus 45.1 +/- 16.2; p < 10-3). The satisfaction rate was significantly higher
      among the experimental group (81.4% versus 51.4%; p < 10-3). The incidence of
      intraoperative awareness was higher in group C (8 cases versus 3 cases) but the
      difference was not statistically significant. CONCLUSION: Music therapy is a non
      pharmacological, inexpensive, and non-invasive technique that can significantly
      enhance patient satisfaction and decrease patients' embarrassing experiences
      related to perioperative stress, pain, and awareness.

PMID- 28452604
TI  - Effects of dexmedetomidine on renal tissue after lower limb ischemia reperfusion
      injury in streptozotocin induced diabetic rats.
AB  - AIM: The aim of this study was to investigate whether dexmedetomidine -
      administered before ischemia - has protective effects against lower extremity
      ischemia reperfusion injury that induced by clamping and subsequent declamping of
      infra-renal abdominal aorta in streptozotocin-induced diabetic rats. MATERIAL AND
      METHODS: After obtaining ethical committee approval, four study groups each
      containing six rats were created (Control (Group C), diabetes-control (Group DM
      C), diabetes I/R (Group DM-I/R), and diabetes-I/R-dexmedetomidine (Group DM-I/R
      D). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered
      intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd
      hour were accepted as diabetic. At the end of four weeks, laparotomy was
      performed in all rats. Nothing else was done in Group C and DM-C. In Group DM
      I/R, ischemia reperfusion was produced via two-hour periods of clamping and
      subsequent declamping of infra-renal abdominal aorta. In Group DM-I/R-D, 100
      MUg/kg dexmedetomidine was administered intraperitoneally 30 minutes before
      ischemia period. At the end of reperfusion, period biochemical and
      histopathological evaluation of renal tissue specimen were performed. RESULTS:
      Thiobarbituric acid reactive substance (TBARS), Superoxide dismutase (SOD),
      Nitric oxide synthase (NOS), Catalase (CAT) and Glutathion S transferase (GST)
      levels were found significantly higher in Group DM-I/R when compared with Group C
      and Group DM-C. In the dexmedetomidine-treated group, TBARS, NOS, CAT, and GST
      levels were significantly lower than those measured in the Group D-I/R. In
      histopathological evaluation, glomerular vacuolization (GV), tubular dilatation
      (TD), vascular vacuolization and hypertrophy (VVH), tubular cell degeneration and
      necrosis (TCDN), tubular hyaline cylinder (THC), leucocyte infiltration (LI), and
      tubular cell spillage (TCS) in Group DM-I/R were significantly increased when
      compared with the control group. Also, GV, VVH, and THC levels in the
      dexmedetomidine-treated group (Group DM-I/R-D) were found significantly decreased
      when compared with the Group DM-I/R. CONCLUSION: We found that dexmedetomidine -
      100 MUg/kg intraperitoneally - administered 30 minutes before ischemia in
      diabetic rats ameliorates lipid peroxidation, oxidative stress, and I-R-related
      renal injury. We suggest that dexmedetomidine administration in diabetic rats
      before I/R has renoprotective effects.

PMID- 28452605
TI  - ICU nurses and physicians dialogue regarding patients clinical status and care
      options-a focus group study.
AB  - Nurses and physicians work side-by-side in the intensive care unit (ICU).
      Effective exchanges of patient information are essential to safe patient care in
      the ICU. Nurses often rate nurse-physician communication lower than physicians
      and report that it is difficult to speak up, that disagreements are not resolved
      and that their input is not well received. Therefore, this study explored nurses'
      dialogue with physicians regarding patients' clinical status and the
      prerequisites for effective and accurate exchanges of information. We adopted a
      qualitative approach, conducting three focus group discussions with five to six
      nurses and physicians each (14 total). Two themes emerged. The first theme
      highlighted nurses' contributions to dialogues with physicians; nurses' ongoing
      observations of patients were essential to patient care discussions. The second
      theme addressed the prerequisites of accurate and effective dialogue regarding
      care options, comprising three subthemes: nurses' ability to speak up and present
      clinical changes, establishment of shared goal and clinical understanding, and
      open dialogue and willingness to listen to each other. Nurses should understand
      their essential role in conducting ongoing observations of patients and their
      right to be included in care-related decision-making processes. Physicians should
      be willing to listen to and include nurses' clinical observations and concerns.

PMID- 28452606
TI  - A phenomenological understanding of residents' emotional distress of living in an
      environmental justice community.
AB  - Deteriorative environmental conditions in environmental justice (EJ) communities
      not only post direct health risks such as chronic illnesses, but also cause
      emotional distress such as anxiety, fear, and anger among residents, which may
      further exacerbate health risks. This study applies a descriptive
      phenomenological method to explore and describe the emotional experience of
      residents living in Ironbound, a known EJ community located in Newark, New
      Jersey. Twenty-three residents participated in the study. Four essential themes
      regarding the residents' emotional experiences were elicited from 43 interviews:
      (1) being worried about the harmful effects of the surrounding pollution; (2)
      being distressed by the known historical pollution sources; (3) being frustrated
      by the unheard voices and/or lack of responses; and (4) being angered by the
      ongoing pollution sources. Participants not only expressed their emotions of
      worry, distress, frustration, and anger in detail but also described reasons or
      situations that provoked such negative emotions. Such detailed depictions provide
      insights into potential meaningful strategies to improve residents' psychological
      wellbeing by alleviating negative emotions and meaningfully engaging residents in
      developing, implementing, and enforcing environmental laws, regulations, and
      policies to achieve EJ goals.

PMID- 28452607
TI  - How do patients actually experience and use art in hospitals? The significance of
      interaction: a user-oriented experimental case study.
AB  - This article aims to understand patient wellbeing and satisfaction and to qualify
      the current guidelines for the application of art in hospitals. Employing
      anthropological methods, we focus on the interactional aspects of art in health
      interventions. A user-oriented study ranked 20 paintings, followed by an
      experiment using paintings in the dayroom of five medical wards. Fieldwork was
      done over a two-week period. During the first week, dayrooms were configured
      without the presence of art and in the second week were configured with the
      artworks. Semi-structured interviews, observation, participant observation and
      informal conversation were carried out and were informed by thermal cameras,
      which monitored the usage, patient occupation and flow in two of the dayrooms.
      The study shows that art contributes to creating an environment and atmosphere
      where patients can feel safe, socialize, maintain a connection to the world
      outside the hospital and support their identity. We conclude that the presence of
      visual art in hospitals contributes to health outcomes by improving patient
      satisfaction as an extended form of health care. The article draws attention to
      further research perspectives and methods associated with the development of art
      in hospitals.

PMID- 28452608
TI  - "We are the soul, pearl and beauty of Hindu Kush Mountains": exploring resilience
      and psychological wellbeing of Kalasha, an ethnic and religious minority group in
      Pakistan.
AB  - The Kalasha are a marginalized ethnic and religious minority group in northern
      Pakistan. The Kalasha minority is known for their divergent polytheistic beliefs,
      and represents the outliers of the collectively monotheistic Muslim population of
      Pakistan. This study aimed to explore the psychological resilience beliefs and
      lived experiences of the Kalasha and to identify cultural protective factors and
      indigenous beliefs that help them maintain psychological wellbeing and
      resilience. Seven semi-structured interviews and two focus-group discussions were
      conducted. The total sample consisted of 6 women and 8 men, aged 20-58 years
      (Mage = 36.29, SD = 12.58). The Interpretative Phenomenological Analysis
      qualitative method was chosen. Study findings identified that factors
      contributing to the wellbeing, happiness and resilience enhancement beliefs of
      Kalasha included five main themes, all influenced by their unique spirituality:
      contentment, pride in social identity, tolerance, gender collaboration and
      gratitude. The study also revealed the Kalasha's perception of their
      marginalization related to challenges and threats. The Kalasha emphasized
      bringing these resilience enhancement beliefs into practice, as a mean to buffer
      against challenges. In conclusion, this study revealed Kalasha's wellbeing and
      resilience enhancement factors, which they believed in and practiced as an
      element of their indigenous culture and religion.

PMID- 28452609
TI  - Supporting activity engagement by family carers at home: maintenance of agency
      and personhood in dementia.
AB  - An explorative paper to describe how family carers, through the caregiving
      journey, reaffirm and promote the agency of people with dementia. Agency is an
      important concept in dementia care and is crucial to the promotion of wellbeing
      and the delivery of person-centred care. This article is based on one of the key
      findings of a study that explored family carers' experiences of engaging their
      relatives in daily activities in domestic settings. Following research governance
      and ethical approval, 30 in-depth interviews (initial and follow-up) were carried
      out with 15 resident-carers of people with dementia who were recruited via local
      community mental health teams. Then five focus groups were conducted with 21
      participants accessed through carers support groups. Interviews and focus groups
      were transcribed, coded and analysed using a grounded theory method. Findings
      showed the process in which family carers encouraged and sustained a sense of
      autonomy and control (agency) in their relative's daily activities. Key
      strategies used by carers included: being non-judgemental; facilitating a sense
      of worth; taking calculated risks; maintaining the continuity of their relative's
      identity; enhancing a sense of connection with their relative's role and identity
      using enjoyable activities; preventing inactivity and attending to the bodily
      source of the agency. Lack of support for carers could ultimately pose a risk to
      the maintenance of the agency of people with dementia. This study provides a
      deeper insight into the process used by home carers to support the agency of
      people with dementia. This is essential if practitioners are to identify and
      develop more realistic intervention strategies and to work in effective
      partnership with family carers. The implications for the creation of dementia
      friendly communities are discussed.

PMID- 28452610
TI  - Active-duty military service members' visual representations of PTSD and TBI in
      masks.
AB  - Active-duty military service members have a significant risk of sustaining
      physical and psychological trauma resulting in traumatic brain injury (TBI) and
      post-traumatic stress disorder (PTSD). Within an interdisciplinary treatment
      approach at the National Intrepid Center of Excellence, service members
      participated in mask making during art therapy sessions. This study presents an
      analysis of the mask-making experiences of service members (n = 370) with
      persistent symptoms from combat- and mission-related TBI, PTSD, and other
      concurrent mood issues. Data sources included mask images and therapist notes
      collected over a five-year period. The data were coded and analyzed using
      grounded theory methods. Findings indicated that mask making offered visual
      representations of the self related to individual personhood, relationships,
      community, and society. Imagery themes referenced the injury, relational
      supports/losses, identity transitions/questions, cultural metaphors, existential
      reflections, and conflicted sense of self. These visual insights provided an
      increased understanding of the experiences of service members, facilitating their
      recovery.

PMID- 28452611
TI  - At zero and turning in circles: refugee experiences and coping in Durban, South
      Africa.
AB  - Millions of refugees are on the move globally, mostly settling in low- and middle
      income (LMIC) "host" countries, where they often receive insufficient assistance
      and encounter a multitude of barriers. Despite a risk for developing mental
      illness, limited research exists on their struggles and coping strategies in
      these settings, especially outside of camps. Against this backdrop, our
      qualitative study aimed to gain a deeper understanding of refugee experiences in
      Durban, South Africa. We conducted semistructured individual interviews with 18
      adult refugees from Zimbabwe and the Democratic Republic of Congo at a community
      based support center in Durban. Participants described their problems, effects on
      mental health, and coping abilities. Interviews were recorded and analyzed for
      themes. Major problems were reported with work, xenophobia/racism, mental health,
      physical safety, housing, healthcare, and quality of life. Participants discussed
      feelings of worry, fear, emotional pain, anger, powerlessness, hopelessness,
      worthlessness, and passive suicidal ideation. Coping mechanisms consisted of
      friendships, church, praying, work, physical activities, family, learning the
      local language, and avoidance of thoughts. Many interviewees expressed a strong
      desire to either return to their homeland or move elsewhere. Refugees in South
      Africa face considerable hardships including xenophobia, physical abuse, and
      work/legal obstructions. More research is needed in LMICs to identify the
      challenges, psychological effects, and coping in such populations so that
      appropriate and accessible mental health services can be created for those who
      require them.

PMID- 28452612
TI  - Letter to the Editor. Flow Diversion in the Treatment of Intracranial Aneurysm
      Trial.

PMID- 28452613
TI  - Fully endoscopic combined transsphenoidal and supraorbital keyhole approach for
      parasellar lesions.
AB  - OBJECTIVE Parasellar tumors that extend far laterally beyond the internal carotid
      artery or that are fibrous and adhere firmly to critical structures are difficult
      to remove totally via the endoscopic transsphenoidal approach alone. In such
      cases, a combined transsphenoidal-transcranial approach is effective to achieve
      maximal resection in a single stage. In this paper, a new minimally invasive
      surgical technique for complicated parasellar lesions, a fully endoscopic
      combined transsphenoidal-supraorbital keyhole approach, is presented. METHODS A
      retrospective review of patients who had been treated via a fully endoscopic
      combined transsphenoidal-supraorbital keyhole approach for complicated parasellar
      lesions was performed. The data for resection rate, perioperative mortality and
      morbidity, and postoperative outcomes were analyzed. RESULTS A total of 12 fully
      endoscopic combined transsphenoidal-supraorbital keyhole approaches were
      performed from March 2013 to February 2016; 10 were for pituitary adenomas and 2
      were for craniopharyngiomas. Gross-total resection or near-total resection was
      achieved in 7 of 12 cases. Among the 11 patients who had presented with
      preoperative visual disturbances, 7 had visual improvement. However, 1 patient
      showed deterioration in visual function. No patient experienced postoperative
      hemorrhage, needed additional surgical treatment, or had postoperative CSF
      leakage. CONCLUSIONS In the combined transsphenoidal and transcranial approach,
      safe and effective cooperative manipulation with 2 surgical corridors can be
      performed for complicated parasellar lesions. The goal of this procedure is not
      to achieve gross-total resection, but to achieve safe resection. Moreover, this
      new surgical approach offers neurosurgeons a simpler operative field with less
      invasiveness than the conventional microscopic combined approach. The fully
      endoscopic combined endonasal-supraorbital keyhole approach is an efficacious
      procedure for complicated parasellar lesions with acceptable results.

PMID- 28452614
TI  - Outcomes after hemispherectomy in adult patients with intractable epilepsy:
      institutional experience and systematic review of the literature.
AB  - OBJECTIVE Hemispherectomy is a surgical technique that is established as a
      standard treatment in appropriately selected patients with drug-resistant
      epilepsy. It has proven to be successful in pediatric patients with unilateral
      hemispheric lesions but is underutilized in adults. This study retrospectively
      evaluated the clinical outcomes after hemispherectomy in adult patients with
      refractory epilepsy. METHODS This study examined 6 cases of hemispherectomy in
      adult patients at Barrow Neurological Institute. In addition, all case series of
      hemispherectomy in adult patients were identified through a literature review
      using MEDLINE and PubMed. Case series of patients older than 18 years were
      included; reports of patients without clear follow-up duration or method of
      validated seizure outcome quantification were excluded. Seizure outcome was based
      on the Engel classification. RESULTS A total of 90 cases of adult hemispherectomy
      were identified, including 6 newly added by Barrow Neurological Institute. Sixty
      five patients underwent functional hemispherectomy; 25 patients had anatomical
      hemispherectomy. Length of follow-up ranged from 9 to 456 months. Seizure freedom
      was achieved in 80% of patients. The overall morbidity rate was low, with 9
      patients (10%) having new or additional postoperative speech or language
      dysfunction, and 19 patients (21%) reporting some worsening of hemiparesis. No
      patients lost ambulatory or significant functional ability, and 2 patients had
      objective ambulatory improvement. Among the 41 patients who underwent additional
      formal neuropsychological testing postoperatively, overall stability or
      improvement was seen. CONCLUSIONS Hemispherectomy is a valuable surgical tool for
      properly selected adult patients with pre-existing hemiparesis and intractable
      epilepsy. In published cases, as well as in this series, the procedure has
      overall been well tolerated without significant morbidity, and the majority of
      patients have been rendered free of seizures.

PMID- 28452615
TI  - Predictive performance of the American College of Surgeons universal risk
      calculator in neurosurgical patients.
AB  - OBJECTIVE The American College of Surgeons (ACS) National Surgical Quality
      Improvement Program (NSQIP) universal Surgical Risk Calculator is an online
      decision-support tool that uses patient characteristics to estimate the risk of
      adverse postoperative events. Further validation of this risk calculator in the
      neurosurgical population is needed; therefore, the object of this study was to
      assess the predictive performance of the ACS NSQIP Surgical Risk Calculator in
      neurosurgical patients treated at a tertiary care center. METHODS A single-center
      retrospective review of 1006 neurosurgical patients treated in the period from
      September 2011 through December 2014 was performed. Individual patient
      characteristics were entered into the NSQIP calculator. Predicted complications
      were compared with actual occurrences identified through chart review and
      administrative quality coding data. Statistical models were used to assess the
      predictive performance of risk scores. Traditionally, an ideal risk prediction
      model demonstrates good calibration and strong discrimination when comparing
      predicted and observed events. RESULTS The ACS NSQIP risk calculator demonstrated
      good calibration between predicted and observed risks of death (p = 0.102),
      surgical site infection (SSI; p = 0.099), and venous thromboembolism (VTE; p =
      0.164) Alternatively, the risk calculator demonstrated a statistically
      significant lack of calibration between predicted and observed risk of pneumonia
      (p = 0.044), urinary tract infection (UTI; p < 0.001), return to the operating
      room (p < 0.001), and discharge to a rehabilitation or nursing facility (p <
      0.001). The discriminative performance of the risk calculator was assessed using
      the c-statistic. Death (c-statistic 0.93), UTI (0.846), and pneumonia (0.862)
      demonstrated strong discriminative performance. Discharge to a rehabilitation
      facility or nursing home (c-statistic 0.794) and VTE (0.767) showed adequate
      discrimination. Return to the operating room (c-statistic 0.452) and SSI (0.556)
      demonstrated poor discriminative performance. The risk prediction model was both
      well calibrated and discriminative only for 30-day mortality. CONCLUSIONS This
      study illustrates the importance of validating universal risk calculators in
      specialty-specific surgical populations. The ACS NSQIP Surgical Risk Calculator
      could be used as a decision-support tool for neurosurgical informed consent with
      respect to predicted mortality but was poorly predictive of other potential
      adverse events and clinical outcomes.

PMID- 28452616
TI  - An ovine model of cerebral catheter venography for implantation of an
      endovascular neural interface.
AB  - OBJECTIVE Neural interface technology may enable the development of novel
      therapies to treat neurological conditions, including motor prostheses for spinal
      cord injury. Intracranial neural interfaces currently require a craniotomy to
      achieve implantation and may result in chronic tissue inflammation. Novel
      approaches are required that achieve less invasive implantation methods while
      maintaining high spatial resolution. An endovascular stent electrode array avoids
      direct brain trauma and is able to record electrocorticography in local cortical
      tissue from within the venous vasculature. The motor area in sheep runs in a
      parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The
      authors aimed to develop a sheep model of cerebral venography that would enable
      validation of an endovascular neural interface. METHODS Cerebral catheter
      venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the
      brain was performed on 13 animals. Multiple telescoping coaxial catheter systems
      were assessed to determine the largest wide-bore delivery catheter that could be
      delivered into the anterior SSS. Measurements of SSS diameter and distance from
      the motor area were taken. The location of the motor area was determined in
      relation to lateral and superior projections of digital subtraction venography
      images and confirmed on MRI. RESULTS The venous pathway from the common jugular
      vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to
      selectively catheterize. The SSS coursed immediately adjacent to the motor cortex
      (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access
      with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times
      and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm)
      was successful in accessing the SSS in 100% of cases with no associated
      complications. Complications included procedure-related venous dissection in two
      major areas: the torcular herophili, and the anterior formation of the SSS. The
      bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of
      the commencement of the motor area. CONCLUSIONS The ovine model for cerebral
      catheter venography has generalizability to the human cerebral venous system in
      relation to motor cortex location. This novel model may facilitate the
      development of the novel field of endovascular neural interfaces that may include
      preclinical investigations for cortical recording applications such as paralysis
      and epilepsy, as well as other potential applications in neuromodulation.

PMID- 28452617
TI  - Intradiploic encephalocele of the primary motor cortex in an adult patient:
      electrophysiological implications during surgery.
AB  - Encephaloceles are herniations of brain parenchyma through congenital or acquired
      osseous-dural defects of the skull base or cranial vault. Different types of
      symptoms, due to CSF fistulas, meningitis, or seizures, are often associated with
      this condition. The authors present a rare case of spontaneous right frontal
      parasagittal encephalocele in a 70-year-old man who was experiencing a spastic
      progressive paresis of his left lower limb. Results of routine
      electrophysiological workup (motor evoked potentials, somatosensory evoked
      potentials, and electroneuromyography), as well as those of MRI of the spinal
      cord, were normal. A brain MRI study detected a partial herniation of the right
      precentral gyrus through a meningeal defect into the diploe, embedding
      corticospinal fibers. The patient underwent navigated craniotomy. Intraoperative
      neuromonitoring of motor function with transcranial electrical stimulation and
      direct cortical stimulation indicated the presence of motor cortex inside the
      encephalocele. Thus, the brain parenchyma was carefully released without
      resection to preserve motor function and, finally, a cranioplasty was performed.
      After a few months, the patient demonstrated considerable improvement in his left
      lower-limb function and, after 1 year, he had fully recovered. Intraoperative
      electrophysiological monitoring and mapping allowed for the determination of the
      best surgical strategy for the isolation of the encephalocele and correlated well
      with preoperative multimodal MRI.

PMID- 28452618
TI  - Long-term reintegration and quality of life in patients with subarachnoid
      hemorrhage and a good neurological outcome: findings after more than 20 years.
AB  - OBJECTIVE The goal of this study was to examine long-term quality of life (QOL)
      and reintegration in patients with good neurological recovery after aneurysmal
      subarachnoid hemorrhage (aSAH) and SAH of unknown cause (SAH NUD). METHODS A long
      term follow-up was performed in an original cohort of 113 individuals who had
      suffered SAH (93 with aSAH and 20 with SAH NUD) between 1977 and 1984. Self
      reporting assessments, performed > 20 years after the bleeding episode, included
      the Quality of Life Scale (QOLS), Psychological General Well-Being (PGWB) index,
      and Reintegration to Normal Living (RNL) index, along with information on sleep
      disturbances and work status. RESULTS Seventy-one survivors were identified.
      Questionnaires were returned by 67 individuals who had suffered SAH 20-28 years
      previously. The QOL was rated in the normal range for both the QOLS score (aSAH
      90.3 vs SAH NUD 88.6) and the PGWB index (aSAH 105.9 vs SAH NUD 102.8). Ninety
      percent of patients had returned to their previous employment. Complete RNL was
      reported by 40% of patients with aSAH and by 46% of patients with SAH NUD; mild
      to moderate readjustment difficulties by 55% and 38%, respectively; and severe
      difficulties by 5% of patients with aSAH and 15% of patients with SAH NUD. Self
      rated aspects of cognition, mood, and energy resources in addition resulted in a
      substantial drop in overall reintegration. Sleep disturbances were reported by
      26%. CONCLUSIONS More than half of patients with SAH who had early good
      neurological recovery experienced reintegration difficulties after > 20 years.
      However, the general QOL was not adversely affected by this impairment. Inability
      to return to work after SAH was associated with lower QOLS scores. Sleep
      disturbances were associated with lower PGWB scores.

PMID- 28452619
TI  - Comparison of MRI techniques for detecting microadenomas in Cushing's disease.
AB  - OBJECTIVE Many centers use conventional and dynamic contrast-enhanced MRI (DMRI)
      sequences in patients with Cushing's disease. The authors assessed the utility of
      the 3D volumetric interpolated breath-hold examination, a spoiled-gradient echo
      3D T1 sequence (SGE) characterized by superior soft tissue contrast and improved
      resolution, compared with DMRI and conventional MRI (CMRI) for detecting
      microadenomas in patients with Cushing's disease. METHODS This study was a
      blinded assessment of pituitary MRI in patients with proven Cushing's disease.
      Fifty-seven patients who had undergone surgery for Cushing's disease (10 male, 47
      female; age range 13-69 years), whose surgical findings were considered to
      represent a microadenoma, and who had been examined with all 3 imaging techniques
      were included. Thus, selection emphasized patients with prior negative or
      equivocal MRI on referral. The MRI annotations were anonymized and 4 separate
      imaging sets were independently read by 3 blinded, experienced clinicians: a
      neuroradiologist and 2 pituitary surgeons. RESULTS Forty-eight surgical specimens
      contained an adenoma (46 ACTH-staining adenomas, 1 prolactinoma, and 1
      nonfunctioning microadenoma). DMRI detected 5 adenomas that were not evident on
      CMRI, SGE detected 8 adenomas not evident on CMRI, including 3 that were not
      evident on DMRI. One adenoma was detected on DMRI that was not detected on SGE.
      McNemar's test for efficacy between the different MRI sets for tumor detection
      showed that the addition of SGE to CMRI increased the number of tumors detected
      from 18 to 26 (p = 0.02) based on agreement of at least 2 of 3 readers.
      CONCLUSIONS SGE shows higher sensitivity than DMRI for detecting and localizing
      pituitary microadenomas, although rarely an adenoma is detected exclusively by
      DMRI. SGE should be part of the standard MRI protocol for patients with Cushing's
      disease.

PMID- 28452620
TI  - Effect of Intensive Periodontal Therapy on Blood Pressure and Endothelial
      Microparticles in Patients With Prehypertension and Periodontitis: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Although some studies show a positive association between
      periodontitis and blood pressure (BP) elevation, research on the effect of
      intensive periodontal treatment on decline in BP levels and endothelial
      microparticles (EMPs) without any antihypertensive management is lacking.
      Therefore, the present clinical trial explores whether intensive periodontal
      therapy would lower BP levels and EMPs of patients with prehypertension with
      periodontitis. METHODS: From a total 107 patients, 95 underwent randomization (47
      assigned to control-treatment [CT] group and 48 assigned to intensive-treatment
      [IT] group) and completed the trial. Patients received intervention for 4
      consecutive weeks and were followed for 6 months. Levels of BP and EMPs were
      evaluated at baseline and 1, 3, and 6 months after intervention. RESULTS:
      Periodontal conditions were significantly improved (P <0.05) 6 months after
      intensive periodontal treatment. In parallel, the primary outcomes including
      systolic and diastolic BP and EMPs were markedly reduced in the IT group compared
      with the CT group (absolute difference: 12.57 and 9.65 mm Hg and 581.59/MUL,
      respectively; 95% confidence intervals: 10.45 to 14.69, 7.06 to 12.24, and 348.12
      to 815.06, respectively; P <0.05). Reduction in BP levels and EMPs was related to
      improvement in probing depth (r = 0.358, 0.363, and 0.676, respectively, by the
      Pearson product-moment correlation; P = 0.009, 0.008, and P <0.001,
      respectively). CONCLUSION: To the best knowledge of the authors, the present
      study demonstrates for the first time that intensive periodontal intervention
      without any antihypertensive medication therapy may be an effective means to
      lower levels of BP and EMPs in patients with prehypertension with periodontitis.

PMID- 28452621
TI  - The Number of Teeth Is Inversely Associated With Metabolic Syndrome: A Korean
      Nationwide Population-Based Study.
AB  - BACKGROUND: Objectives of this research are to determine the relationship between
      number of natural teeth and metabolic syndrome (MetS) in a representative sample
      of the Korean population. METHODS: From the Korean National Health and Nutrition
      Examination Survey, a cross-sectional study was conducted on 13,066 participants
      aged >19 years. The number of teeth was assessed by clinical oral examination.
      MetS was defined based on the joint interim statement of the International
      Diabetes Federation Task Force on Epidemiology and Prevention. Multivariable
      logistic regression analyses were used to evaluate the association between number
      of teeth and MetS adjusted for the following criteria: 1) age; 2) sex; 3) income;
      4) education; 5) toothbrushing frequency; 6) periodontitis; 7) smoking; 8)
      drinking; 9) physical activity; and 10) diabetes mellitus. RESULTS: The number of
      existing permanent teeth was inversely associated with MetS after controlling for
      all confounders (adjusted odds ratio [AOR] = 1.19, 95% confidence interval [CI] =
      1.04 to 1.36 for 20 to 27 teeth; AOR = 1.37, 95% CI = 1.12 to 1.67 for 0 to 19
      teeth). Association between fewer teeth and MetS increased for individuals aged
      >=40 years and for women. CONCLUSION: The number of teeth found is inversely
      proportional to occurrence of MetS.

PMID- 28452622
TI  - Histologic Evaluation of Wound Healing After Ridge Preservation With Cortical,
      Cancellous, and Combined Cortico-Cancellous Freeze-Dried Bone Allograft: A
      Randomized Controlled Clinical Trial.
AB  - BACKGROUND: Cortical and cancellous mineralized freeze-dried bone allografts
      (FDBA) are available for use in alveolar ridge preservation after tooth
      extraction. There are currently no data regarding use of a combination 50%/50%
      cortico-cancellous FDBA compared with a 100% cortical or 100% cancellous FDBA in
      ridge preservation. The primary objective of this study is to dimensionally and
      histologically evaluate healing after ridge preservation in non-molar sites using
      50%/50% cortico-cancellous FDBA versus 100% cortical and 100% cancellous FDBA.
      METHODS: Sixty-six patients requiring extraction of a non-molar tooth were
      enrolled and randomized into three groups to receive ridge preservation with the
      following: 1) 100% cortical FDBA; 2) 100% cancellous FDBA; or 3) 50%/50% cortico
      cancellous FDBA. After 18 to 20 weeks of healing, a biopsy was harvested, and an
      implant was placed. The alveolar ridge was measured pre- and postoperatively to
      evaluate change in ridge height and width. Percentages of vital bone, residual
      graft, and connective tissue (CT)/other were determined via histomorphometric
      analysis. RESULTS: Histomorphometric analysis revealed no significant differences
      among groups regarding percentage of vital bone or CT/other. The 100% cortical
      FDBA group had significantly greater residual graft material (P = 0.04).
      Dimensional analysis revealed no significant between-group differences in any
      parameter measured. CONCLUSION: To the best knowledge of the authors, this study
      offers the first histologic evidence demonstrating no significant difference in
      vital bone formation or dimensional changes among 50%/50% cortico-cancellous
      FDBA, 100% cortical FDBA, and 100% cancellous FDBA when used in ridge
      preservation of non-molar tooth sites.

PMID- 28452623
TI  - Advantages of Autologous Platelet-Rich Fibrin Membrane on Gingival Crevicular
      Fluid Growth Factor Levels and Periodontal Healing: A Randomized Split-Mouth
      Clinical Study.
AB  - BACKGROUND: This study evaluates contributions of platelet-rich fibrin (PRF)
      combined with conventional flap surgery on growth factor levels in gingival
      crevicular fluid (GCF) and periodontal healing. METHODS: Twenty-six patients (52
      sites) with chronic periodontitis were treated either with autologous PRF with
      open flap debridement (OFD+PRF) or OFD alone. Growth factor levels in GCF at
      baseline and 2, 4, and 6 weeks after surgery were analyzed, and clinical
      parameters such as probing depth (PD), relative clinical attachment level (rCAL),
      and gingival margin level (GML) at baseline and 9 months after surgery were
      measured. RESULTS: Mean PD reduction and rCAL gain were significantly greater in
      OFD+PRF sites than in OFD sites. Mean GML change was -0.38 + 0.10 mm in OFD sites
      and 0.11 + 0.08 mm in the test group; difference between the two groups was
      statistically significant (P <0.05). Both groups demonstrated increased
      expression levels of fibroblast growth factor-2, transforming growth factor
      beta1, and platelet-derived growth factor-BB at 2 weeks compared with baseline,
      followed by reductions at 4 and 6 weeks. The OFD+PRF group showed significantly
      higher growth factor levels compared with the OFD group at 2 and 4 weeks.
      CONCLUSION: PRF membrane combined with OFD provides significantly higher GCF
      concentrations of angiogenic biomarkers for ~2 to 4 weeks and better periodontal
      healing in terms of conventional flap sites.

PMID- 28452624
TI  - MRI appearance of invasive subcentimetre breast carcinoma: benign characteristics
      are common.
AB  - OBJECTIVE: This study was undertaken to examine the characteristics of cancers
      detected at the earliest possible point on MRI and to determine their
      significance. METHODS: This institutional review board-approved Health Insurance
      Portability and Accountability Act-compliant retrospective study evaluated
      invasive breast cancers <=1 cm histologically. MRI was performed within 6 months
      before diagnosis. Between 1 January 2005 and 31 December 2015, 163 cancers in 161
      patients were evaluated. Breast Imaging-Reporting and Data System lesion
      characteristics were assessed by two radiologists independently. In cases of
      disagreement, arbitration by a third reader was performed. RESULTS: Cancers <=1
      cm became more obviously malignant as they enlarged with regard to shape (p =
      0.021), margin (p = 0.0006), internal enhancement (p = 0.0158) and kinetics (p =
      0.0001). Cancers <=5 mm had benign characteristics of circumscribed margins in
      71% (71/100), round/oval shape in 67% (67/100) and persistent enhancement in 41%
      (41/100). High T2 signal was found in 17% (28/62), distributed equally among
      different sizes (p = 0.3920). In <=5-mm cancers (59%, 12/29), a comparison study
      to show interval growth was more often needed to determine the need for biopsy.
      When interval growth determined biopsy, this was evident within 24 months and
      cancers remained node negative despite this delay. CONCLUSION: Benign
      characteristics are present in most invasive cancers <=5 mm. Small cancers on MRI
      may need to demonstrate growth to determine need for biopsy. Advances in
      knowledge: MR lesion characteristics may not be helpful in determining whether
      small lesions on MR are benign or malignant. However, as 97% of cancers in our
      study showed interval change when a prior MR for comparison was available, new
      lesions or increasing size should lead to consideration of biopsy.

PMID- 28452625
TI  - Theory, Science, and Practice for Advancing Capacity Evaluation in Older Adults.

PMID- 28452626
TI  - Swimming against the Tide: A Case Study on the Removal of Conservatorship and
      Guardianship.
AB  - OBJECTIVE: This article evaluates the role healthcare providers play in balancing
      safety versus autonomy among elders when performing capacity evaluations.
      METHODS: Presentation of a case study consisting of an 85-year-old, Caucasian,
      widowed, male, post-stroke veteran, residing in long-term care. He was assigned a
      permanent court-appointed joint guardian and conservator, but wanted to remove
      both of these as he felt he had the ability to manage his own affairs. This case
      study specifically addresses the issue of financial capacity. RESULTS: After
      completion of the evaluation, a case was made for the least restrictive means
      balancing patient autonomy and protection, opting for a limited conservatorship.
      The court, using the evaluation as evidence, completely removed the guardianship
      and conservatorship. CONCLUSIONS: This article outlines how providers can
      navigate multiple roles, team dynamics, and advocate for enhancing the capacity
      of an older adult.

PMID- 28452627
TI  - Sexual Consent Capacity: Ethical Issues and Challenges in Long-Term Care.
AB  - More than two million Americans live in nursing homes and other long-term care
      facilities. Available research suggests that the majority of older nursing home
      residents, including those with some degree of cognitive impairment, place
      significant value upon a variety of sexual activities. With nearly half of all
      residents suffering from dementia, psychologists and other mental health
      professionals often face significant challenges in the assessment of their
      patients' sexual consent capacity. A primary ethical issue is to balance an
      individual resident's rights to autonomy and privacy with a facility's need to
      protect residents from harm. Sexual consent capacity functions on a continuum
      across time and behavior. It also cannot be predetermined by proxy, in which an
      individual prepares legal documents ahead of time to identify a surrogate
      decision maker; sexual consent capacity must be determined by information
      obtained in the present moment. In this paper, an approach to the assessment of
      residents' sexual consent capacity, encompassing knowledge, reasoning, and
      voluntariness, along with a brief overview of sexual activity among long-term
      care residents, will be presented. A case example is offered to illustrate
      complex clinical dilemmas involving staff attitudes, residents' rights, and
      family dynamics.

PMID- 28452628
TI  - Informed Consent to Research with Cognitively Impaired Adults: Transdisciplinary
      Challenges and Opportunities.
AB  - Due to issues related to informed research consent, older adults with cognitive
      impairments are often excluded from high-quality studies that are not directly
      related to cognitive impairment, which has led to a dearth of evidence for this
      population. The challenges to including cognitively impaired older adults in
      research and the implications of their exclusion are a transdisciplinary issue.
      The ethical challenges and logistical barriers to conducting research with
      cognitively impaired older adults are addressed from the perspectives of three
      different fields-social work, emergency medicine, and orthopaedic surgery. Issues
      related to funding, study design, intervention components, and outcomes are
      discussed through the unique experiences of three different providers. A fourth
      perspective-medical research ethics-provides alternatives to exclusion when
      conducting research with cognitively impaired older adults such as timing,
      corrective feedback and plain language, and capacity assessment and proxy
      appointments. Given the increasing aging population and the lack of evidence on
      cognitively impaired older adults, it is critical that researchers, funders, and
      institutional review boards not be dissuaded from including this population in
      research studies.

PMID- 28452629
TI  - Neurocognitive Predictors of Declining Financial Capacity in Persons with Mild
      Cognitive Impairment.
AB  - OBJECTIVE: To identify cognitive predictors of declining financial capacity (FC)
      in persons with mild cognitive impairment (MCI). METHODS: Participants were 66
      cognitively normal older adults and 49 persons with MCI who completed
      neuropsychological testing and a performance measure of financial capacity
      (Financial Capacity Instrument; FCI) at baseline and two-year follow-up. We
      calculated two-year change scores for neuropsychological tests and FCI total
      score. We examined bivariate correlations between demographic/clinical variables
      and FCI change score, and between neuropsychological and FCI change scores. The
      five strongest bivariate correlates were entered into a linear regression
      analysis to identify longitudinal predictors of financial decline within group.
      RESULTS: Persons with MCI showed significant decline on the FCI and most
      cognitive variables, while controls demonstrated relatively stable performance.
      For persons with MCI, education correlated with FCI change score. The top four
      cognitive variable-FCI change score correlations were written arithmetic,
      confrontation naming, immediate visual memory, and visual attention. In the
      regression model, written arithmetic was the primary predictor and visual memory
      and visual attention were secondary predictors of two-year FCI change scores.
      CONCLUSION: Semantic arithmetic knowledge, and to a lesser extent visual memory
      and attention, are key longitudinal cognitive predictors of financial skill
      decline in individuals with MCI. CLINICAL IMPLICATIONS: Clinicians should
      consider neurocognitive abilities of written arithmetic, visual memory, and
      processing speed in their assessments of financial capacity in person with MCI.

PMID- 28452630
TI  - Financial Capacity and Financial Exploitation of Older Adults: Research Findings,
      Policy Recommendations and Clinical Implications.
AB  - BACKGROUND: Financial exploitation (FE) of older adults is a social issue that is
      beginning to receive the attention that it deserves in the mediathanks to some
      high profile cases, but empirical research and clinical guidelines on the topic
      are just emerging. OBJECTIVE: Our review seeks to synthesize the current research
      in the area and develop a concentpual model. METHOD: In this review, we describes
      the significance of the problem, proposes a theoretical model for conceptualizing
      FE, and summarizes related areas of research that may be useful to consider in
      the understanding of FE. RESULTS: We identify key structural issues that have
      limited interventions in the past and make specific public policy recommendations
      in lightof the largest intergenerational transfer of wealth in history.
      CONCLUSIONS: FE is a significant social problem, in this article we discuss
      implications for clinical practice.

PMID- 28452631
TI  - The role of revision surgery and adjuvant therapy following subtotal resection of
      osteosarcoma of the spine: a systematic review with meta-analysis.
AB  - OBJECTIVE Primary osteosarcoma of the spine is a rare osseous neoplasm. While
      previously reported retrospective studies have demonstrated that overall patient
      survival is impacted mostly by en bloc resection and chemotherapy, the continued
      management of residual disease remains to be elucidated. This systematic review
      was designed to address the role of revision surgery and multimodal adjuvant
      therapy in cases in which en bloc excision is not initially achieved. METHODS A
      systematic literature search spanning the years 1966 to 2015 was performed on
      PubMed, Medline, EMBASE, and Web of Science to identify reports describing
      outcomes of patients who underwent biopsy alone, neurological decompression, or
      intralesional resection for osteosarcoma of the spine. Studies were reviewed
      qualitatively, and the clinical course of individual patients was aggregated for
      quantitative meta-analysis. RESULTS A total of 16 studies were identified for
      inclusion in the systematic review, of which 8 case reports were summarized
      qualitatively. These studies strongly support the role of chemotherapy for
      overall survival and moderately support adjuvant radiation therapy for local
      control. The meta-analysis revealed a statistically significant benefit in
      overall survival for performing revision tumor debulking (p = 0.01) and also for
      chemotherapy at relapse (p < 0.01). Adjuvant radiation therapy was associated
      with longer survival, although this did not reach statistical significance (p =
      0.06). CONCLUSIONS While the initial therapeutic goal in the management of
      osteosarcoma of the spine is neoadjuvant chemotherapy followed by en bloc
      marginal resection, this objective is not always achievable given anatomical
      constraints and other limitations at the time of initial clinical presentation.
      This systematic review supports the continued aggressive use of revision surgery
      and multimodal adjuvant therapy when possible to improve outcomes in patients who
      initially undergo subtotal debulking of osteosarcoma. A limitation of this
      systematic review is that lesions amenable to subsequent resection or tumors
      inherently more sensitive to adjuvants would exaggerate a therapeutic effect of
      these interventions when studied in a retrospective fashion.

PMID- 28452632
TI  - The impact of spinopelvic morphology on the short-term outcome of pedicle
      subtraction osteotomy in 104 patients.
AB  - OBJECTIVE Pedicle subtraction osteotomy (PSO) is commonly performed for
      correction of spinal sagittal plane deformities. The PSO results in complex,
      multiple changes of the spinopelvic alignment. The influence of the variability
      of individual pelvic morphology has not been fully analyzed in previous outcome
      studies of sagittal imbalance. The aim of this study was to define radiological
      variables affecting the outcome after PSO in adult spinal deformities, with
      special emphasis on the variability of pelvic morphology. METHODS Clinical and
      radiographic outcomes were analyzed in a retrospective analysis of 104 patients
      who underwent a PSO at a single center. The radiographic variables studied were
      sagittal vertical axis (SVA), T1SPI (T-1 spinopelvic inclination), lumbar
      lordosis (LL), thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT),
      and sacral slope (SS). To control for the individual variation of pelvic
      morphology, the LL/PI, PT/PI, and SS/PI ratios were calculated. Clinical outcome
      was assessed using the visual analog scale for pain, Oswestry Disability Index,
      and EQ-5D preoperatively and at a minimum 1-year follow-up. Correlation
      coefficients were calculated between each individual radiographic variable and
      the outcome measures. The importance of LL mismatch to TK, reflecting the
      importance of a harmonious spine, was analyzed by comparing the outcome of
      patients with a TK+LL+PI <= 45 degrees  to those with a sum > 45 degrees .
      RESULTS SVA and T1SPI demonstrated the strongest correlation with the clinical
      outcome scores (r = 0.4-0.5, p < 0.001). LL correlated weakly with the clinical
      outcome (r = 0.2-0.3, p < 0.003). Mismatch of LL to PI, however, did not
      correlate significantly with the outcome. Similarly, only weak and inconsistent
      correlation was observed between PT, SS, PT/PI, SS/PI, and functional outcome.
      Patients with a TK+LL+PI <= 45 degrees  had a significantly lower ODI score (33
      vs 44) and a significantly higher EQ-5D score (0.64 vs 0.40) than patients with a
      sum > 45 degrees  (LL is a negative value). CONCLUSIONS PSO resulted in a
      substantial correction of sagittal imbalance and improved outcome in most
      patients in this study. Correction of the global sagittal balance appears to be a
      necessary precondition for a good outcome. A harmonious spine with a TK and an LL
      of similar magnitude seems to add to a positive outcome.

PMID- 28452635
TI  - The Brady Bunch.

PMID- 28452633
TI  - Post-spinal cord injury astrocyte-mediated functional recovery in rats after
      intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG.
AB  - OBJECTIVE The most actively explored therapeutic strategy for overcoming spinal
      cord injury (SCI) is the delivery of genes encoding molecules that stimulate
      regeneration. In a mouse model of amyotrophic lateral sclerosis and in
      preliminary clinical trials in patients with amyotrophic lateral sclerosis, the
      combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG)
      encoding the neurotrophic/angiogenic factors vascular endothelial growth factor (
      VEGF) and angiogenin ( ANG) was found to slow the development of neurological
      deficits. These results suggest that there may be positive effects of this
      combination of genes in posttraumatic spinal cord regeneration. The objective of
      the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination
      therapy on motor function recovery and reactivity of astrocytes in a rat model of
      SCI. METHODS Spinal cord injury was induced in adult Wistar rats by the weight
      drop method. Rats (n = 51) were divided into 2 groups: the experimental group
      (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]).
      Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan
      scale. The duration and intensity of infectivity and gene expression from the
      injected vectors were assessed by immunofluorescent detection of GFP. Reactivity
      of glial cells was assessed by changes in the number of immunopositive cells
      expressing glial fibrillary acidic protein (GFAP), S100beta, aquaporin 4 (AQP4),
      oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4.
      The level of S100beta mRNA expression in the spinal cord was estimated by real
      time polymerase chain reaction. RESULTS Partial recovery of motor function was
      observed 30 days after surgery in both groups. However, Basso, Beattie, and
      Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with
      the control group. Specific GFP signal was observed at distances of up to 5 mm in
      the rostral and caudal directions from the points of injection. A 1.5 to 2.0-fold
      increase in the number of GFAP+, S100beta+, and AQP4+ cells was observed in the
      white and gray matter at a distance of up to 5 mm from the center of the lesion
      site in the caudal and rostral directions. At 30 days after injury, a 2-fold
      increase in S100beta transcripts was observed in the Ad5-VEGF+Ad5-ANG group
      compared with the control group. CONCLUSIONS Intraspinal injection of recombinant
      adenoviral vectors encoding VEGF and ANG stimulates functional recovery after
      traumatic SCI. The increased number of S100beta+ astrocytes induced by this
      approach may be a beneficial factor for maintaining the survival and function of
      neurons. Therefore, gene therapy with Ad5-VEGF+Ad5-ANG vectors is an effective
      therapeutic method for SCI treatment.

PMID- 28452636
TI  - Mental Health Services in NCAA Division I Athletics: A Survey of Head ATCs.
AB  - BACKGROUND: There is a growing awareness of the importance of mental health care
      in National Collegiate Athletic Association (NCAA) student-athletes; however,
      there is a lack of literature on mental health resources in collegiate settings.
      Identifying current practices can set the stage to improve the delivery of care.
      HYPOTHESIS: There is great variability in resources and current practices and no
      "standard of care" exists. STUDY DESIGN: Observational, quantitative. LEVEL OF
      EVIDENCE: Level 5. METHODS: One hundred twenty-seven (36% response rate) head
      athletic trainers at Division I NCAA member colleges completed a web-based
      survey. Questions assessed several aspects of mental health clinicians,
      perception of care coordination, and screening. RESULTS: Seventy-two percent of
      respondents noted that counseling took place in a counseling center, and 20.5% of
      respondents indicated that they had a mental health provider who worked in the
      athletic training room. Mental health clinician credentials included marriage and
      family therapist, psychologist, clinical social worker, and psychiatrist. The
      majority of athletic trainers (ATCs) noted that they are satisfied with the
      feedback from the mental health provider about the student-athletes' mental
      health (57.3%) and believe that they would be able to provide better care to
      student-athletes if mental health services occurred onsite in the training room
      (46.4%). Fewer than half (43%) indicated that they use screening instruments to
      assess for mental health disorders. CONCLUSION: There is wide variability on how
      mental health services are provided to NCAA Division 1 student-athletes. Some
      mental health care providers are located offsite, while some provide care in the
      training room setting. Also, there are inconsistencies in the use of standardized
      screening tools for mental health evaluation. There is no standard collaborative
      or integrated care delivery model for student-athletes. CLINICAL RELEVANCE:
      Opportunities exist for standardization through integrated care models and
      increased use of validated screening tools to deliver comprehensive care to
      student-athletes.

PMID- 28452637
TI  - Incidence and Etiology of Sudden Cardiac Death: New Updates for Athletic
      Departments.
AB  - CONTEXT: Sudden cardiac death (SCD) in a young athlete is a tragic event and is
      the leading medical cause of death in this population. The precise incidence of
      SCD in young athletes has been subject of debate, with studies reporting
      drastically different rates (1:917,000 athlete-years (AYs) to 1:3000 AYs)
      depending on the methodological design of the investigation or the targeted
      population. EVIDENCE ACQUISITION: A literature search was performed in PubMed
      using the terms: incidence, sudden cardiac death, sudden death, sudden cardiac
      arrest, etiology, pathology, registry, athlete, young, children, and adolescents.
      Articles were reviewed for relevance and included if they contained information
      on the incidence of SCD in athletes or young persons up to the age of 35 years.
      STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5. RESULTS: Studies of
      high quality and rigor consistently yield an incidence of 1:50,000 AYs in college
      athletes and between 1:50,000 and 1:80,000 AYs for high school athletes, with
      certain subgroups that appear to be at particularly high risk, including the
      following: men, basketball players, and African Americans. Initial reports
      suggest that the most common cause of SCD is hypertrophic cardiomyopathy (HCM).
      However, more comprehensive investigations in the United States and international
      populations-athletes, nonathletes, and military-support that the most common
      finding on autopsy in young individuals with SCD is actually a structurally
      normal heart (autopsy-negative sudden unexplained death). CONCLUSION: SCD is the
      leading cause of death in athletes during exercise and usually results from
      intrinsic cardiac conditions that are triggered by the physiologic demands of
      vigorous exercise. Current rates of SCD appear to be at least 4 to 5 times higher
      than previously estimated, with men, African Americans, and male basketball
      players being at greatest risk. Emerging data suggest that the leading finding
      associated with SCD in athletes is actually a structurally normal heart (autopsy
      negative sudden unexplained death).

PMID- 28452638
TI  - When Employment and Caregiving Collide: Predictors of Labor Force Participation
      in Prospective and Current Caregivers.
AB  - OBJECTIVE: Female caregivers often reduce time spent at work to care for aging
      family members, which precipitates financial hardship and other adverse outcomes.
      Little is known about psychosocial correlates of labor force participation (LFP)
      among female caregivers. The theory of planned behavior posits that social norms,
      attitudes, and perceived control predict intentions and volitional behaviors, but
      also that the compelling influence of situational variables undermines enactment
      of behaviors consistent with one's intentions. The objective of this study was to
      employ the theory of planned behavior to examine how psychosocial characteristics
      predict willingness to reduce LFP among prospective caregivers and actual LFP
      reduction among active caregivers. METHODS: Subsamples of 165 female prospective
      caregivers and 97 active female caregivers responded to a survey assessing filial
      beliefs and LFP. RESULTS: Filial obligation and caregiver preparedness predicted
      intentions to reduce LFP among prospective caregivers, but did not predict actual
      reduction in LFP in active caregivers. Weekly care demands exceeding 20 hours
      emerged as the sole correlate of LFP among active caregivers. CONCLUSIONS:
      Domains of the theory of planned behavior predict LFP intentions, but LFP
      decisions are subject to external pressures, specifically, time demands of the
      caregiving relationship. Prospective caregivers may benefit from proactive
      interventions aimed at reducing conflict between situational demands and filial
      beliefs.

PMID- 28452639
TI  - Preliminary Evidence for the Validity and Reliability of the Caregiver Reaction
      Scale.
AB  - OBJECTIVE: Reliable and valid measures of caregiver experience are critical
      components of researching the caregiver experience and providing effective care
      to family caregivers. Assessments should be comprehensive, including positive
      aspects of caregiving as well as multiple dimensions of stress and burden (Family
      Caregiver Alliance, 2006). One such measure is the Caregiver Reaction Scale
      (CRS), a clinical tool adapted from research protocols in 1990. METHODS: This
      study is a preliminary examination of the psychometric properties of the CRS
      using a sample of family caregivers (N = 502) seeking services at a community
      based mental health and aging family service agency. RESULTS: The eight subscales
      of the CRS exhibited very good internal reliability alpha >= .81. Test-retest
      reliability was r >= .62, and convergent validity evidence is positive. Means and
      standard deviations are reported. CONCLUSIONS: Initial psychometrics suggest the
      CRS offers a reliable and valid assessment of multiple dimensions of the
      caregiving experience and warrants further research.

PMID- 28452640
TI  - Confirmatory Factor Analysis for the Multidimensional Scale of Perceived Social
      Support in a Sample of Early Retirees Enrolled in University Programs.
AB  - OBJECTIVE: The aims of this study were twofold-first, to use confirmatory factor
      analysis (CFA) to help assess which of the previously identified factor
      structures (identified through exploratory factor analysis) best fits a Spanish
      language version of the Multidimensional Scale of Perceived Social Support
      (MSPSS), and second, to validate the MSPSS (and its subscales) for use among
      early retirees. METHODS: The psychometric properties of the MPSS were analyzed in
      a sample of 991 Spanish early retirees enrolled in university programs.
      Participants had an average age of 62.7 years (SD = 5.89). An exploratory factor
      analysis and second-order confirmatory factor analysis were developed to identify
      the factorial solution and the best model fit. RESULTS: The three factors
      identified were MSPSS significant others, MSPSS friends, and MSPSS family.
      Regarding reliability and validity, internal consistency indices were above .92
      and the correlation between perceived social support subscales and measures of
      satisfaction with life in retirement were significantly positive. CONCLUSION: The
      Spanish language version of the MSPSS demonstrates acceptable psychometric
      properties in relation to internal structure and reliability, and all but one of
      the goodness-of-fit indices emerging from the CFA also supported this factor
      structure. The practical implications of the scale in different populations and
      the problems in relation to the three-factor solution and the index values
      obtained are discussed.

PMID- 28452641
TI  - A Validity and Reliability Study of the Japanese Version of the Geriatric
      Depression Scale 15 (GDS-15-J).
AB  - OBJECTIVE: The 15-item Geriatric Depression Scale (GDS-15) is one of the most
      widely used screening instruments for depression among the elderly. The aim of
      this study was to examine the validity and reliability of the Japanese version of
      the GDS-15 (GDS-15-J) in comparison with the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for
      depression. METHODS: The study participants were 128 elderly outpatients (age
      range, 55 to 92 years) categorized into two groups (76 non-depressive patients,
      52 depressive patients) based on the DSM-IV-TR criteria for depression. RESULTS:
      Logistic regression analysis showed that regardless of age and sex, the GDS-15-J
      score could be used to screen patients for depression (p < .001). The validity of
      the GDS-15-J for depression assessed against DSM-IV-TR criteria was excellent
      based on receiver operating characteristic analysis (optimal cutoff point: 6/7;
      sensitivity: .98; specificity: .86). The recommended optimal cutoff score when
      screening for depression is 6/7. To evaluate the constructive validity of the GDS
      15-J, factor analysis was performed. Three factors were extracted. Cronbach's
      alpha reliability coefficient was .83 to the GDS-15-J scale, which indicated a
      high degree of internal consistency. CONCLUSION: The GDS-15-J is a clinically
      applicable screening instrument for depression. CLINICAL IMPLICATIONS: In this
      study this version of the GDS-15-J displayed excellent psychometric properties
      using a 6/7 cut off. Analyses suggest some items that might be removed in future
      studies of an abbreviated scale.

PMID- 28452642
TI  - Hospice as Experienced by LTC Nurses and Their Perception of Resident
      Experiences.
AB  - OBJECTIVES: This study utilized qualitative methods to better understand long
      term care (LTC) nursing staff's experience with hospice services and their
      perceptions of resident choice to utilize hospice services, as well as understand
      differences LTC nurses have experienced in regards to resident deaths. METHODS:
      Interpretative Phenomenological Analysis (IPA) was utilized to extract themes and
      subthemes from 10 interviews that occurred with LTC nursing staff. Content
      analysis was also utilized to extract one noteworthy concept, which was a
      comparison of two resident deaths, with and without the utilization of hospice
      services. RESULTS: Three main themes were extracted from the data: LTC nursing
      participant's positive view of hospice, their perception that residents view
      hospice very negatively, and why residents choose to utilize hospice services.
      Participants also identified aspects of a "bad" or "good" death, with clear
      relationships noted when using hospice services. CONCLUSIONS: Findings identified
      a difference between the LTC nursing staff's positive view of hospice and their
      belief that their residents view hospice services very negatively. According to
      these nurses' experiences, to most residents, hospice meant something rather
      negative and feared. CLINICAL IMPLICATIONS: An intervention providing information
      about hospice services for LTC resident population may increase the percentage of
      older adults who utilize hospice services.

PMID- 28452644
TI  - Self-Management and Yoga for Older Adults with Chronic Stroke: A Mixed-Methods
      Study of Physical Fitness and Physical Activity.
AB  - OBJECTIVE: This study investigated changes in physical fitness and physical
      activity among older patients with chronic stroke (stroke >= 6 months previous)
      after participation in a yoga infused self-management intervention. METHODS: A
      mixed-methods secondary data analysis examined quantitative measures of
      endurance, strength, and gait speed and qualitative perspectives of intervention
      participants. RESULTS: Based on Wilcoxon analysis, physical fitness outcome
      measures including endurance and lower and upper body strength significantly (p <
      .02) improved. Based on qualitative results of 2 focus groups and 14 individual
      interviews, participants expressed positive changes in endurance, strength, gait
      speed, flexibility, and balance. They also reported improvements in walking
      ability and duration, and expressed a desire to continue yoga and increase levels
      of exercise. CONCLUSIONS: With the objective of improving physical fitness and
      exercise for older adults with chronic stroke, it is important for self
      management interventions to provide specific safe and feasible physical activity
      components, such as yoga. CLINICAL IMPLICATIONS: Health professionals may improve
      offered chronic stroke self-management interventions by incorporating yoga.

PMID- 28452643
TI  - The Effects of the MORE Wisdom Resources on Spousal Caregivers' Life
      Satisfaction: An Application of the Resilience Model.
AB  - OBJECTIVES: Models of resilience suggest that psychosocial resources and their
      interactions facilitate resilience while experiencing life challenges of
      caregiving. The MORE wisdom resources (sense of Mastery, Openness to experience,
      Reflective attitude, and Emotion regulation) have been suggested as possible
      personal resources of resilience that predict positive health outcomes of
      caregivers. Applying a model of resilience, this study examined the direct and
      indirect effects of the three of the MORE wisdom resources (sense of Mastery,
      Openness to experience, and Emotion regulation) on caregiving spouses' life
      satisfaction and perceived physical health. METHODS: Using data from the survey
      of Midlife in the United States, caregiving spouses (n = 114) and matched non
      caregivers (n = 114) were included. We compared the direct and indirect effects
      of the wisdom resources on life satisfaction and physical health between the two
      groups. RESULTS: The simple mediation model proposed in 2008 by Preacher and
      Hayes revealed that openness to experience was directly associated with better
      life satisfaction among caregiving spouses. Sense of mastery and emotion
      regulation had indirect effects on life satisfaction through spousal support. The
      effects the wisdom resources on caregiving spouses' perceived physical health
      were not found. CONCLUSIONS: This study demonstrated that the three of the MORE
      wisdom resources are possible personal resilience factors influencing life
      satisfaction among caregiving spouses. Moreover, the study showed how spousal
      support mediates the relationship between the wisdom resources and life
      satisfaction. CLINICAL IMPLICATIONS: Interventions aiming to increase life
      satisfaction among caregiving spouses should focus on increasing both personal
      and environmental resources and strengthening the relationship of the caregiver
      and care recipient.

PMID- 28452645
TI  - Staff Factors Contributing to Family Satisfaction with Long-Term Dementia Care: A
      Systematic Review of the Literature.
AB  - OBJECTIVE: The aim of the present review was to critically evaluate empirical
      evidence regarding staff factors that contribute to families' satisfaction with
      ongoing care provision for their relatives with dementia in long-term care.
      METHODS: Four databases were systematically searched using search terms informed
      by the aim of the present systematic review. The resulting 14 relevant articles
      comprised both qualitative and quantitative studies. RESULTS: The findings
      highlighted three broad areas relating to staff factors that appeared to
      contribute to families' satisfaction with care provision: family related factors,
      relating to staff interaction with families; staffing related factors, focusing
      on staffing organization and composition; and client related factors, focusing on
      staff interaction with clients and the quality of care provided. CONCLUSIONS: The
      findings have important implications for care staff and managers working in such
      settings regarding staffing organization, staff training, recruitment and
      retention. Future research directions are discussed. CLINICAL IMPLICATIONS:
      Families want consistent, knowledgeable staff that interact well and respond
      appropriately to the needs of their relative as well as their own needs as family
      members. Staff training in such settings should therefore focus not only on staff
      education but also on the importance of establishing effective relationships with
      both clients and families.

PMID- 28452646
TI  - Medication Saving Behaviors of Older Adults: Scale Developed to Assess Family
      Caregiver Perspectives.
AB  - OBJECTIVES: This study developed and explored the preliminary reliability and
      validity of a 6-item Medication Saving Behaviors (MSB) scale when completed by
      family care partners of older adults. METHODS: Women (N = 119) helping an aging
      relative with healthcare appointments and medication management completed an
      online survey including items related to generalized hoarding and medication
      saving behaviors. RESULTS: The MSB was psychometrically sound and correlated
      significantly with hoarding scales and reported number of expired and leftover
      medications. Compared with those reporting low levels of general hoarding
      concerns, group means on the MSB were higher for caregivers reporting clinically
      significant levels of hoarding by their elderly family member. The MSB was
      unrelated to total prescription or over-the-counter medications for the older
      adult, lending support for the discriminant validity of the scale. CONCLUSIONS:
      This study provides initial support for the convergent and discriminant validity
      of the MSB when administered to intergenerational care partners of older adults.
      CLINICAL IMPLICATIONS: The MSB may function to identify higher risk patients via
      their family members and target families for interventions.

PMID- 28452647
TI  - A Case of Fronto-Temporal Dementia (FTD) Masquerading as Mood Disorder.
AB  - A 56-year old Chinese female was referred to an academic medical center with
      atypical, treatment-resistant depression that continued for approximately 3 years
      after her sister's death. Comprehensive evaluation including neurocognitive
      testing, EEG, spinal tap, HIV testing and brain MRI revealed behavioral variant
      of fronto-temporal dementia (bvFTD) with significant frontal and temporal lobe
      atrophy.This patient's unusual clinical presentation emphasizes the overlap
      between depression and bvFTD, and underlines the importance of prompt, accurate
      diagnosis to minimize often-ineffective pharmacological interventions and
      caregiver burnout.

PMID- 28452648
TI  - IRT Analysis of the Frontal Systems Behavior Scale: Identifying the Best Items
      for Use with Geriatric Patients in Primary Care.
AB  - OBJECTIVE: The Frontal Systems Behavior Scale (FrSBe) (Grace & Malloy, 2001)
      assesses behavioral dysfunction associated with frontal-subcortical damage; it is
      often used to measure these indicators of executive dysfunction in older adults
      with possible dementia. Although prior research supports the FrSBe's clinical
      utility and factorial validity, little attempt has been made to examine which
      items are most useful for geriatric cases. The goal of the present study is to
      identify these items. METHOD: Data from 304 older patients referred for
      neuropsychological assessment were used to examine the FrSBe's three subscales:
      Apathy (A; 14 items), Executive Dysfunction (E; 17 items), and Disinhibition (D;
      15 items). Item properties were investigated using the Graded Response Model, a
      two-parameter polytomous item response theory model. RESULTS: Difficulty
      parameters, discrimination parameters, and information curves identified 18 items
      that effectively discriminate (a >= 1.70) between levels of behavioral
      dysfunction and measure a range of dysfunction (bA: -1.23 - 2.22; bD: -.29 -
      2.14; bE: -1.81 - 1.77). CONCLUSIONS: Most FrSBe items were effective at
      discriminating various levels of behavioral dysfunction, though weaker items were
      identified. CLINICAL IMPLICATIONS: The findings suggest the FrSBe is a useful
      clinical tool when working with a geriatric population, though some items provide
      more information than others.

PMID- 28452649
TI  - Neighborhood Socioeconomic Status and Cognitive Trajectories in a Diverse
      Longitudinal Cohort.
AB  - OBJECTIVES: Although individual-level socioeconomic status is associated with
      poor outcomes, less is known regarding how the social context might affect
      cognitive outcomes. We examined the effect of neighborhood socioeconomic status
      (NSES) on baseline cognitive function and trajectories of decline. METHODS: The
      sample (N = 480) came from a longitudinal cohort recruited to study cognitive
      function. Mixed effects models examined the influence of NSES on baseline and
      rate of change in executive function, semantic memory, and episodic memory.
      RESULTS: NSES was positively associated with semantic memory scores at baseline,
      but not with executive function or episodic memory in adjusted models, nor was it
      associated with cognitive change in longitudinal analyses. In exploratory
      analyses, for individuals with dementia, those with higher NSES declined faster
      in executive function and semantic memory than did those with lower NSES.
      CONCLUSIONS: Results suggest that NSES has limited effects independent of
      personal characteristics; however, findings showed a complex relation of NSES and
      decline, with NSES effects observed only for individuals with dementia. Results
      are discussed in the context of cognitive reserve. CLINICAL IMPLICATIONS:
      Clinical assessments of individuals who present with cognitive impairment might
      benefit from an understanding of the neighborhood context from which patients
      come.

PMID- 28452650
TI  - The Promotion of Well-Being in Aging Individuals Living in Nursing Homes: A
      Controlled Pilot Intervention with Narrative Strategies.
AB  - OBJECTIVES: The study aimed: (1) to compare levels of well-being and distress in
      older adults living in nursing homes with those living in community; and (2) to
      test the feasibility of a positive narrative intervention for improving well
      being versus a control art-and-craft intervention in a nursing home setting.
      METHODS: Sixty older adults participated in the study (M = 77.37; SD = 5.00),
      Male = 20 (33.3%). In Study 1, 30 adults living in nursing homes were compared
      with 30 community-dwellers using the following measures: Satisfaction with Life
      Scale, Psychological Well-being Scale, Social Well-being Scale, Geriatric
      Depression Scale, and sleep quality. In Study 2, the same 30 adults living in
      nursing homes were allocated to a positive narrative intervention group (N = 20)
      or to a control group (N = 10) and assessed at post-intervention. RESULTS: In
      Study 1, older adults in nursing homes presented more depression and impairments
      in well-being, compared to community-dwellers. In Study 2, at post-treatment,
      individuals assigned to the narrative intervention reported significantly
      increased well-being and sleep quality. CONCLUSIONS: Although preliminary,
      results showed that older adults living in nursing homes are more vulnerable than
      community-dwellers. These patients experienced improvement when given a short
      group positive narrative intervention applicable in nursing homes. CLINICAL
      IMPLICATIONS: A brief group intervention based on fairy tales yielded
      improvements in well-being and sleep quality in nursing home residents, who
      enjoyed and appreciated its content. These promising results need to be confirmed
      by future randomized controlled trials.

PMID- 28452651
TI  - Physicians' and nurses' attitudes towards performance-based financial incentives
      in Burundi: a qualitative study in the province of Gitega.
AB  - BACKGROUND: Performance-based financing (PBF) was first implemented in Burundi in
      2006 as a pilot programme in three provinces and was rolled out nationwide in
      2010. PBF is a reform approach to improve the quality, quantity, and equity of
      health services and aims at achieving universal health coverage. It focuses on
      how to best motivate health practitioners. OBJECTIVE: To elicit physicians' and
      nurses' experiences and views on how PBF influenced and helped them in healthcare
      delivery. METHODS: A qualitative cross-sectional study was carried out among
      frontline health workers such as physicians and nurses. The data was gathered
      through individual face-to-face, in-depth, semi-structured interviews with 6
      physicians and 30 nurses from February to March 2011 in three hospitals in Gitega
      Province. A simple framework approach and thematic analysis using a combination
      of manual technique and MAXQDA software guided the analysis of the interview
      data. RESULTS: Overall, the interviewees felt that the PBF scheme had provided
      positive motivation to improve the quality of care, mainly in the structures and
      process of care. The utilization of health services and the relationship between
      health practitioners and patients also improved. The salary top-ups were
      recognized as the most significant impetus to increase effort in improving the
      quality of care. The small and sometimes delayed financial incentives paid to
      physicians and nurses were criticized. The findings of this study also indicate
      that the positive interaction between performance-based incentive schemes and
      other health policies is crucial in achieving comprehensive improvement in
      healthcare delivery. CONCLUSIONS: PBF has the potential to motivate medical staff
      to improve healthcare provision. The views of medical staff and the context of
      the area of implementation have to be taken into consideration when designing and
      implementing PBF schemes.

PMID- 28452652
TI  - Health equity and migrants in the Greater Mekong Subregion.
AB  - BACKGROUND: Migrant health is receiving increasing international attention,
      reflecting recognition of the health inequities experienced among many migrant
      populations and the need for health systems to adapt to diverse migrant
      populations. In the Greater Mekong Subregion (GMS) there is increasing migration
      associated with uneven economic integration and growth, socio-economic
      vulnerabilities, and disparities between countries. There has been limited
      progress, however, in improving migrant access to health services in the
      Subregion. This paper examines the health needs, access barriers, and policy
      responses to cross-border migrants in five GMS countries. METHODS: A review of
      published literature and research was conducted on migrant health and health
      service access in Cambodia, Lao People's Democratic Republic, Myanmar, Thailand,
      and Viet Nam, as well as analysis of current migration trends and universal
      health coverage (UHC) indicators in the Subregion. The review included different
      migrant types: i.e. migrant workers, irregular migrants, victims of trafficking,
      refugees and asylum seekers, and casual cross-border migrants. RESULTS: There is
      substantial diversity in the capacity of GMS health systems to address migrant
      populations. Thailand has sought to enhance migrant health coverage, including
      development of migrant health policies/programs, bilateral migrant worker
      agreements, and migrant health insurance schemes; Viet Nam provides health
      protection for emigrant workers. Overall, however, access to good quality health
      care remains weak for many citizens in GMS countries let alone migrants. Migrant
      workers - and irregular migrants in particular - face elevated health risks yet
      are not adequately covered and incur high out-of-pocket (OOP) payments for health
      services. CONCLUSIONS: UHC implies equity: UHC is only achieved when everyone has
      the opportunity to access and use good-quality health care. Efforts to achieve
      UHC in the GMS require deliberate policy decisions to include migrants. The
      emergence of the UHC agenda, and the focus on migrant health among policy makers
      and partners, present an opportunity to tackle barriers to health service access,
      extend coverage, and strengthen partnerships in order to improve migrant health.
      This is an opportune time for GMS countries to develop migrant-inclusive health
      systems.

PMID- 28452653
TI  - The Medical Education Partnership Initiative (MEPI), a collaborative paradigm for
      institutional and human resources capacity building between high- and low- and
      middle-income countries: the Mozambique experience.
AB  - BACKGROUND: Collaborations among researchers based in lower and middle income
      countries (LMICs) and high income countries (HICs) have made major discoveries
      related to diseases disproportionately affecting LMICs and have been vital to the
      development of research communities in LMICs. Such collaborations have generally
      been scientifically and structurally driven by HICs. OBJECTIVES: In this report
      we outline a paradigm shift in collaboration, exemplified by the Medical
      Education Partnership Initiative (MEPI), in which the formulation of priorities
      and administrative infrastructure reside in the LMIC. METHODS: This descriptive
      report outlines the critical features of the MEPI partnership. RESULTS: In the
      MEPI, LMIC program partners translate broad program goals and define metrics into
      priorities that are tailored to local conditions. Program funds flow to a LMIC
      based leadership group that contracts with peers from HICs to provide technical
      and scientific advice and consultation in a 'reverse funds flow' model. Emphasis
      is also placed on strengthening administrative capacity within LMIC institutions.
      A rigorous monitoring and evaluation process modifies program priorities on the
      basis of evolving opportunities to maximize program impact. CONCLUSIONS: Vesting
      LMIC partners with the responsibility for program leadership, and building
      administrative and fiscal capacity in LMIC institutions substantially enhances
      program relevance, impact and sustainability.

PMID- 28452654
TI  - Epilepsy surgery for epileptic encephalopathy as a sequela of herpes simplex
      encephalitis: case report.
AB  - Herpes simplex virus (HSV) encephalitis can manifest with different clinical
      presentations, including acute monophasic illness and biphasic chronic
      granulomatous HSV encephalitis. Chronic encephalitis is much less common, and
      very rare late relapses are associated with intractable epilepsy and progressive
      neurological deficits with or without evidence of HSV in the cerebrospinal fluid.
      The authors report on an 8-year-old girl with a history of treated HSV-1
      encephalitis when she was 13 months of age and focal epilepsy when she was 2
      years old. Although free of clinical seizures, when she was 5, she experienced
      behavioral and academic dysfunction, which was later attributed to electrographic
      focal seizures and worsening electroencephalography (EEG) findings with
      electrical status epilepticus during slow-wave sleep (ESES). Following a right
      temporal lobectomy, chronic granulomatous encephalitis was diagnosed. The
      patient's clinical course improved with the resolution of seizures and EEG
      abnormalities.

PMID- 28452655
TI  - Scoliosis in myelomeningocele: epidemiology, management, and functional outcome.
AB  - OBJECTIVE The authors aimed to provide an updated and consolidated report on the
      epidemiology, management, and functional outcome of cases of myelomeningocele
      (MMC) in patients with scoliosis. METHODS A comprehensive literature search was
      performed using MEDLINE, Embase, Google Scholar, and the Cochrane Database of
      Systematic Reviews on cases of MMC in patients with scoliosis between 1980 and
      2016. The initial search yielded 670 reports. After removing duplicates and
      applying inclusion criteria, we included 32 full-text original articles in this
      study. RESULTS Pooled statistical analysis of the included articles revealed the
      prevalence of scoliosis in MMC patients to be 53% (95% CI 0.42-0.64). Slightly
      more females (56%) are affected with both MMC and scoliosis than males. Motor
      level appears to be a significant predictor of prevalence, but not severity, of
      scoliosis in MMC patients. Treatment options for these patients include tethered
      cord release (TCR) and fusion surgeries. Curvature improvement and stabilization
      after TCR may be limited to patients with milder (< 50 degrees ) curves.
      Meanwhile, more aggressive fusion procedures such as a combined anterior
      posterior approach may result in more favorable long-term scoliosis correction,
      albeit with greater complication rates. Quality of life metrics including
      ambulatory status and sitting stability are influenced by motor level of the
      lesion as well as the degree of the scoliosis curvature. CONCLUSIONS Scoliosis is
      among the most common and challenging comorbidities from which patients with MMC
      suffer. Although important epidemiological and management trends are evident,
      larger, prospective studies are needed to discover ways to more accurately
      counsel and more optimally treat these patients.

PMID- 28452656
TI  - Traumatic nondisplaced coronal suture fracture causing delayed intracranial
      hemorrhage in a pediatric patient.
AB  - Skull fracture after a head injury is relatively common in children younger than
      2 years of age. The author reports the case of a 14-month-old girl who sustained
      a unilateral nondisplaced coronal suture fracture from a fall. She developed
      delayed intracranial hemorrhage from an underlying dural tear and cortical vein
      injury. Although an isolated skull fracture in a pediatric trauma patient
      typically portends a benign clinical course and may not require that the patient
      be hospitalized, a nondisplaced fracture across the coronal suture can lead to
      dural tear and intracranial injuries. High vigilance is warranted when evaluating
      CT images around the suture lines and treating pediatric patients with fractures
      across the coronal suture.

PMID- 28452657
TI  - Shunting outcomes in posthemorrhagic hydrocephalus: results of a Hydrocephalus
      Clinical Research Network prospective cohort study.
AB  - OBJECTIVE Previous Hydrocephalus Clinical Research Network (HCRN) retrospective
      studies have shown a 15% difference in rates of conversion to permanent shunts
      with the use of ventriculosubgaleal shunts (VSGSs) versus ventricular reservoirs
      (VRs) as temporization procedures in the treatment of hydrocephalus due to high
      grade intraventricular hemorrhage (IVH) of prematurity. Further research in the
      same study line revealed a strong influence of center-specific decision-making on
      shunt outcomes. The primary goal of this prospective study was to standardize
      decision-making across centers to determine true procedural superiority, if any,
      of VSGS versus VR as a temporization procedure in high-grade IVH of prematurity.
      METHODS The HCRN conducted a prospective cohort study across 6 centers with an
      approximate 1.5- to 3-year accrual period (depending on center) followed by 6
      months of follow-up. Infants with premature birth, who weighed less than 1500 g,
      had Grade 3 or 4 IVH of prematurity, and had more than 72 hours of life
      expectancy were included in the study. Based on a priori consensus, decisions
      were standardized regarding the timing of initial surgical treatment, upfront
      shunt versus temporization procedure (VR or VSGS), and when to convert a VR or
      VSGS to a permanent shunt. Physical examination assessment and surgical technique
      were also standardized. The primary outcome was the proportion of infants who
      underwent conversion to a permanent shunt. The major secondary outcomes of
      interest included infection and other complication rates. RESULTS One hundred
      forty-five premature infants were enrolled and met criteria for analysis. Using
      the standardized decision rubrics, 28 infants never reached the threshold for
      treatment, 11 initially received permanent shunts, 4 were initially treated with
      endoscopic third ventriculostomy (ETV), and 102 underwent a temporization
      procedure (36 with VSGSs and 66 with VRs). The 2 temporization cohorts were
      similar in terms of sex, race, IVH grade, head (orbitofrontal) circumference, and
      ventricular size at temporization. There were statistically significant
      differences noted between groups in gestational age, birth weight, and
      bilaterality of clot burden that were controlled for in post hoc analysis. By
      Kaplan-Meier analysis, the 180-day rates of conversion to permanent shunts were
      63.5% for VSGS and 74.0% for VR (p = 0.36, log-rank test). The infection rate for
      VSGS was 14% (5/36) and for VR was 17% (11/66; p = 0.71). The overall compliance
      rate with the standardized decision rubrics was noted to be 90% for all surgeons.
      CONCLUSIONS A standardized protocol was instituted across all centers of the
      HCRN. Compliance was high. Choice of temporization techniques in premature
      infants with IVH does not appear to influence rates of conversion to permanent
      ventricular CSF diversion. Once management decisions and surgical techniques are
      standardized across HCRN sites, thus minimizing center effect, the observed
      difference in conversion rates between VSGSs and VRs is mitigated.

PMID- 28452658
TI  - Resolution of giant basilar artery aneurysm compression and reversal of
      sensorineural hearing loss with use of a flow diverter: case report.
AB  - The authors present an unusual case of a 15-year-old boy in whom sensorineural
      hearing loss and disequilibrium developed in the setting of a giant basilar
      artery aneurysm. This patient was treated with a flow-diverting stent and had
      complete resolution of his clinical symptoms including hearing loss. This case
      demonstrates the efficacy of flow diversion in select pediatric patients with
      posterior circulation aneurysms. The features that are thought to result in
      successful treatment are discussed.

PMID- 28452659
TI  - New Directions in Alleviating Anxiety in Older Adults: Applications,
      Modifications, and Innovations.

PMID- 28452660
TI  - The Association between Generalized Anxiety Disorder, Subthreshold Anxiety
      Symptoms and Fear of Falling among Older Adults: Preliminary Results from a Pilot
      Study.
AB  - OBJECTIVE: A relationship between generalized anxiety disorder (GAD) and fear of
      falling (FOF) has long been proposed but never specifically studied. This study
      aimed at analyzing the relationship between FOF and GAD or anxiety symptoms,
      while controlling for major depressive episodes (MDE), depressive symptoms, fall
      risk, and sociodemographic variables. METHODS: Twenty-five older adults
      participated in this pilot study. Assessments included the following: Anxiety
      Disorder Interview Schedule, Geriatric Anxiety Inventory, Geriatric Depression
      Scale, Falls-Efficacy Scale-International. A multidisciplinary team evaluated
      fall risk. RESULTS: FOF was significantly correlated with GAD, MDE, anxiety and
      depressive symptoms, and fall risk, but not with sociodemographic variables.
      Multiple regression analyses indicated that GAD and anxiety symptoms were
      significantly and independently associated with FOF. CONCLUSION: Although the
      results of this pilot study should be replicated with larger samples, they
      suggest that FOF is associated with GAD and anxiety symptoms even when
      considering physical factors that increase the risk of falling. CLINICAL
      IMPLICATIONS: Treatment of FOF in patients with GAD may present a particular
      challenge because of the central role of intolerance of uncertainty, which may
      prevent patients from regaining confidence despite the reduction of fall risk.
      Clinicians should screen for GAD and anxiety symptoms in patients with FOF to
      improve detection and treatment.

PMID- 28452661
TI  - Befriending to Relieve Anxiety and Depression Associated with Chronic Obstructive
      Pulmonary Disease (COPD): A Case Report.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic lung disease
      characterized by airflow obstruction and shortness of breath, which as a result
      can severely limit activities of daily living. COPD sufferers are 85% more likely
      to develop anxiety disorders than healthy matched controls. Some of the factors
      that have been suggested to be associated with high anxiety in people with COPD
      include dyspnoea, the inability to perform daily activities or fulfil social
      roles, rehospitalisation and some COPD treatments. There is substantial evidence
      that cognitive behaviour therapy (CBT) is effective in managing mood disorders,
      but there is also some evidence that befriending can assist people. Befriending
      is an intervention that focuses on everyday conversation topics and can be
      delivered by volunteers with training and supervision. The case presented here
      illustrates the use of befriending provided over the phone for a participant with
      severe anxiety and depression. It was part of a larger RCT comparing CBT and
      befriending for the management of anxiety and depression in people with COPD.
      Symptoms were alleviated after a course of 8 weeks of befriending telephone calls
      from a volunteer. While befriending is not a substitute for CBT it may be useful
      in circumstances where CBT is not easily accessible.

PMID- 28452662
TI  - Predictors of Outcomes for Older Adults Participating in Calmer Life, a
      Culturally Tailored Intervention for Anxiety.
AB  - OBJECTIVE: Determine predictors of reduced worry and anxiety for older adults
      participating in the pilot phase of Calmer Life, a modular, personalized
      cognitive-behavioral treatment for worry. METHODS: Underserved adults (N = 54)
      over age 50 participated. Therapists were either experts (Ph.D. or Master's) or
      nonexpert providers (case managers, community health workers, and bachelor's
      level). Participants completed the Penn State Worry Questionnaire-Abbreviated
      (PSWQ-A) and the Geriatric Anxiety Inventory-Short Form (GAI-SF) before treatment
      and at 3 months. RESULTS: Demographic and clinical variables were individually
      entered into separate regression equations, controlling for pretreatment scores,
      to determine their associations with post-treatment 1) PSWQ-A and 2) GAI-SF
      scores. Only younger age and African American race were significant (p < .05)
      univariate predictors of higher post-treatment PSWQ-A scores. African American
      race was also a significant predictor of higher post-treatment GAI-SF scores.
      CONCLUSIONS: African American participants had higher post-treatment PSWQ-A and
      GAI-SF scores than White and Hispanic participants. Younger age was also
      associated with more severe PSWQ-A post-treatment scores. CLINICAL IMPLICATIONS:
      Younger participants may experience additional stressors (e.g., caregiving,
      working) compared with older participants. Smaller decreases in anxiety in
      African Americans point to the need for continued focus and additional
      modification of interventions.

PMID- 28452663
TI  - Psychometric Evaluation of the Saving Inventory-Revised in Older Adults.
AB  - OBJECTIVES: Hoarding disorder (HD) is a chronic condition characterized by severe
      impairment in health and functioning for older adults. Researchers and clinicians
      commonly use the Saving Inventory-Revised (SI-R), a self-report measure validated
      for the assessment of HD, to establish symptom severity. This study represents
      the first evaluation of the psychometric properties of the SI-R in a sample of
      older adults with HD. METHODS: Participants were 156 older adults with HD and 23
      older adults with no psychiatric diagnoses. Demographic and HD symptom severity
      measures were compared between the two samples. Convergent and discriminant
      validity was examined in the HD sample. A confirmatory factor analysis was used
      to test the replicability of the three-factor structure observed in the original
      sample. RESULTS: Participants in the HD sample scored significantly higher on the
      SI-R than did the non-psychiatric sample. The SI-R was significantly correlated
      with clutter level and symptoms of anxiety and depression. A three-factor model
      demonstrated poor fit in the HD sample. CONCLUSIONS: The SI-R can be used to
      validly assess hoarding severity in geriatric populations. CLINICAL IMPLICATIONS:
      Clinicians working with geriatric patients should consider refraining from use of
      the SI-R subscales as they may be less theoretically distinct in older adults.

PMID- 28452664
TI  - Parkinson's Disease and Driving Cessation: a Journey Influenced by Anxiety.
AB  - OBJECTIVES: In addition to the motor and cognitive symptoms that people with
      Parkinson's disease (PD) typically experience, psychiatric symptoms such as
      anxiety are also commonly experienced by people with PD. The overall purpose of
      the current study was to explore driving and driving cessation for people with PD
      and their families. METHODS: A descriptive phenomenological approach was employed
      using semi-structured interviews and 34 interviews were conducted overall (22
      participants with PD and 12 family members). RESULTS: Experiences of anxiety and
      worry that had an impact on driving and driving cessation arose from the data,
      and this article specifically captured the lived experience of anxiety with
      driving and driving cessation for people with PD and their families. CONCLUSIONS:
      Findings reveal that the experience of anxiety while driving, as well as
      anticipatory anxiety and/or worry related to driving cessation, affect the
      driving experiences and wellbeing of people with PD. CLINICAL IMPLICATIONS:
      Implications of the study findings are outlined and aim to provide information
      about the needs to enable future clinical directions to be developed.

PMID- 28452665
TI  - Effects of Home-Delivered Cognitive Behavioral Therapy (CBT) for Depression on
      Anxiety Symptoms among Rural, Ethnically Diverse Older Adults.
AB  - BACKGROUND: We examined the effects of home-delivered cognitive-behavioral
      therapy (CBT) for depression on anxiety symptoms in an ethnically diverse, low
      resource, and medically frail sample of rural, older adults. METHOD: This was a
      secondary analysis of a randomized clincial trial with 134 rural-dwelling adults
      65 years and older with decreased quality of life and elevated psychological
      symptomatology. Anxiety symptoms were assessed with the anxiety and phobic
      anxiety subscales of the Symptom Checklist-90-Revised (SCL-90-R). RESULTS:
      Compared to a minimal support control condition, CBT for depression resulted in
      significantly greater improvements in symptoms of anxiety and phobic anxiety from
      pre-treatment to post-treatment. CONCLUSION: Home-delivered CBT for depression
      can be an effective treatment for anxiety in a hard-to-reach older populations.
      CLINICAL IMPLICATIONS: Additional research should explore integrated anxiety and
      depression protocols and other treatment modalities, including bibliotherapy or
      telehealth models of CBT, to reduce costs associated with its in home delivery.
      Flexibility in administration and adaptations to the CBT protocol may be
      necessary for use with vulnerable, rural older adults.

PMID- 28452666
TI  - Cognitive Behavior Therapy for Anxiety in Parkinson's Disease: Outcomes for
      Patients and Caregivers.
AB  - OBJECTIVE: Anxiety negatively impacts the quality of life of Parkinson's disease
      (PD) patients and caregivers. Despite high prevalence, there is a paucity of
      trials investigating effective treatments for anxiety in PD. This uncontrolled
      study investigated the use of a manualized and tailored Cognitive Behavior
      Therapy (CBT) for anxiety in PD. METHODS: Participants completed 6 weekly CBT
      sessions. Pre-, post- and follow-up (3 and 6 months) assessments were made.
      Change in outcomes were analysed using t-tests and Reliability Change Index. Of
      17 PD patients who agreed to CBT, 12 completed the intervention. RESULTS: This
      study showed a significant reduction in Hamilton Anxiety Rating Scale scores in
      PD immediately post CBT (t(11) = 3.59, p < .01), maintained at 3-month (t(8) =
      2.83, p = .02) and 6-month (t(7) = 2.07, p = .04) follow-up. A reduction in
      caregiver burden (t(11) = 2.68, p = .03) was observed post intervention.
      Improvements in motor disability (t(11) = 2.41, p = .04) and cognitive scores
      (t(11) = -2.92, p = .01) were also observed post intervention and at follow-up.
      CONCLUSIONS: Tailored CBT can be used to treat anxiety in PD. CLINICAL
      IMPLICATIONS: This study provides preliminary evidence suggesting that tailored
      CBT reduces anxiety in PD with persisting benefits, and lowers caregiver burden.

PMID- 28452668
TI  - Vida Calma: CBT for Anxiety with a Spanish-Speaking Hispanic Adult.
AB  - BACKGROUND: Hispanic adults aged 55 years and older are the fastest growing
      ethnic minority group in the United States facing significant mental health
      disparities. Barriers in accessing care have been attributed to low income, poor
      education, language barriers, and stigma. Cultural adaptations to existing
      evidence-based treatments have been encouraged to improve access. However, little
      is known about mental health treatments translated from English to Spanish
      targeting anxiety among this Hispanic age group. Objctive: This case study offers
      an example of how an established, manualized, cognitive-behavioral treatment for
      adults 55 years and older with generalized anxiety disorder (known as "Calmer
      Life") was translated to Spanish ("Vida Calma") and delivered to a monolingual,
      Hispanic 55-year-old woman. RESULTS: Pre- and post-treatment measures showed
      improvements in symptoms of anxiety, depression, and life satisfaction.
      CONCLUSION: Findings suggest Vida Calma is a feasible treatment to use with a 55
      year-old Spanish-speaking adult woman. CLINICAL IMPLICATIONS: Vida Calma, a
      Spanish language version of Calmer Life, was acceptable and feasible to deliver
      with a 55-year-old participant with GAD. Treatment outcomes demonstrate that Vida
      Calma improved the participant's anxiety, depression, and life satisfaction.

PMID- 28452667
TI  - Systematic Review of the Clinical Application of Exposure Techniques to Community
      Dwelling Older Adults with Anxiety.
AB  - OBJECTIVES: Although exposure techniques are a first-line intervention for
      anxiety, clear evidence is lacking for their efficacy in treating the prevalent
      and debilitating condition of late life anxiety. This study sought to review the
      current literature on use of exposure with community-dwelling older patients.
      METHODS: Searches of electronic databases were conducted to identify articles
      published through December 7, 2016. Inclusion criteria were: 1) sample age > 55,
      2) therapy that included exposure, 3) anxiety as a target of the treatment.
      Exclusion criteria were: 1) not available in English, 2) no quantitative data, 3)
      inpatient setting. Methodological data and findings were extracted from the
      articles chosen for review. RESULTS: The 54 eligible articles presented a total
      of 16 case studies, 9 uncontrolled trials, 24 controlled trials, and 6 secondary
      studies. A majority of the studies were conducted in the U.S.A with participants
      who received individual treatment. In vivo and imaginal exposure were the most
      frequently delivered techniques, and most treatments were multicomponent. Most
      studies found a reduction in anxiety symptoms. CONCLUSIONS: Important research
      gaps need to be addressed. CLINICAL IMPLICATIONS: The surveyed research provides
      a modest foundation of evidence for mental health practitioners who wish to
      incorporate exposure into treatment plans.

PMID- 28452669
TI  - Are We Doing a Good Job? In Praise of Program Evaluation.

PMID- 28452670
TI  - A Peer Mentorship Program for Mental Health Professionals in Veterans Health
      Administration Home-Based Primary Care.
AB  - OBJECTIVES: Mental health professionals working in integrated, interdisciplinary
      primary or geriatric care settings may have limited training for this growing
      model of care. Peer mentorship is one avenue of professional development support.
      We describe the development and evaluation of a peer mentorship program for
      mental health professionals working within Veterans Health Administration (VHA)
      Home Based Primary Care (HBPC) programs. METHODS: Electronic surveys were
      administered to 57 peer mentorship pairs matched for program participation. The
      survey examined program utilization characteristics, nature of peer contact, and
      benefits and challenges reported by participants. RESULTS: Overall, mentor and
      mentee respondents (N = 58) cited numerous benefits of engaging in the program.
      Mentees reported their peer mentorship relationships provided acceptance,
      support, encouragement and positive role modeling. CONCLUSIONS: Findings suggest
      peer mentoring can be an important professional resource to offer mental health
      professionals new to working in integrated, geriatric care settings. CLINICAL
      IMPLICATIONS: Mental health professionals new to working in geriatric and/or
      integrated care settings may have limited training to meet specialized needs of
      patients, families, and interdisciplinary care teams. Peer mentorship following
      formal academic training may be an important option for professional development,
      supporting enhanced competence and, ultimately, improved patient care and team
      functioning.

PMID- 28452671
TI  - Evaluation of an Audio-Visual Novela to Improve Beliefs, Attitudes and Knowledge
      toward Dementia: A Mixed-Methods Approach.
AB  - OBJECTIVES: Dementia is a clinical syndrome characterized by progressive
      degeneration in cognitive ability that limits the capacity for independent
      living. Interventions are needed to target the medical, social, psychological,
      and knowledge needs of caregivers and patients. This study used a mixed methods
      approach to evaluate the effectiveness of a dementia novela presented in an audio
      visual format in improving dementia attitudes, beliefs and knowledge. METHODS:
      Adults from Los Angeles (N = 42, 83% female, 90% Hispanic/Latino, mean age = 42.2
      years, 41.5% with less than a high school education) viewed an audio-visual
      novela on dementia. Participants completed surveys immediately before and after
      viewing the material. RESULTS: The novela produced significant improvements in
      overall knowledge (t(41) = -9.79, p < .0001) and led to positive increases in
      specific attitudes toward people with dementia but not in beliefs that screening
      would be beneficial. Qualitative results provided concordant and discordant
      evidence for the quantitative findings. CONCLUSIONS: Results indicate that an
      audio-visual novela can be useful for improving attitudes and knowledge about
      dementia, but further work is needed to investigate the relation with health
      disparities in screening and treatment behaviors. CLINICAL IMPLICATIONS: Audio
      visual novelas are an innovative format for health education and change attitudes
      and knowledge about dementia.

PMID- 28452672
TI  - Managing Depression among Diverse Older Adults in Primary Care: The BRIGHTEN
      Program.
AB  - OBJECTIVES: A variety of specific cultural adaptations have been proposed for
      older adult and minority mental health interventions. The objective of this study
      was to determine whether the BRIGHTEN Program, an individually tailored,
      interdisciplinary "virtual" team intervention, would equally meet the needs of a
      highly diverse sample of older adults with depression. METHODS: Older adults who
      screened positive for depression were recruited from primary and specialty care
      settings to participate in the BRIGHTEN program. A secondary data analysis of 131
      older adults (37.4% African-American, 29.0% Hispanic, 29.8% Non-Hispanic White)
      was conducted to explore the effects of demographic variables (race/ethnicity,
      income and education) on treatment outcome. RESULTS: Compared to baseline,
      participants demonstrated significant improvements on the SF-12 Mental Health
      Composite and depression (GDS-15) scores at 6-month follow-up. There were no
      differences on outcome measures based on race/ethnicity, income or education with
      one exception-a difference between 12th grade and graduate degree education on SF
      12 Mental Health Composite scores. CONCLUSIONS: While not explicitly tailored for
      specific ethnic groups, the BRIGHTEN program may be equally effective in reducing
      depression symptoms and improving mental health functioning in a highly
      socioeconomically and ethnically diverse, community-dwelling older adult
      population. CLINICAL IMPLICATIONS: Implications for behavioral health integration
      in primary care are discussed.

PMID- 28452673
TI  - Improving Mental Health in the Community: Outcome Evaluation of a Geriatric
      Mental Health Day Treatment Service.
AB  - OBJECTIVES: This program evaluation reviewed the outcomes of a new 10-week multi
      modal mental health day treatment program for elderly clients with mood and
      anxiety disorders. METHODS: A retrospective chart review of clients admitted
      during the first 3 years of the program (N = 255) was conducted. Paired sample t
      tests were used to compare admission and discharge data. Focus groups were run
      with clients who attended the program during the previous months, to delineate
      the strengths of the program and to identify areas for improvement. RESULTS:
      Analyses showed statistically and clinically significant improvements in client
      symptomatology, as evidenced by reductions on the Geriatric Depression Scale and
      the Clinical Outcomes in Routine Evaluation Outcome Measure in clients who
      completed the program. Focus group participants overwhelmingly described the
      program as very beneficial, but the desire for on-going follow-up was clearly
      articulated. CONCLUSIONS: A practice model employing group-based cognitive
      behavioural and interpersonal strategies that emphasizes behavioral activation
      and socialization is associated with a reduction in depressive symptoms and
      psychological distress in a large sample of elderly adults in a day treatment
      service with mild to moderate symptoms of depression and anxiety. CLINICAL
      IMPLICATIONS: In the future, a mechanism for on-going mental health support
      should be included. Many clients want to remain connected to the system, but
      there is not always a clear path along the continuum of care, particularly for
      clients who no longer meet criteria for a psychiatric disorder.

PMID- 28452674
TI  - Understanding the Progression from Physical Illness to Suicidal Behavior: A Case
      Study Based on a Newly Developed Conceptual Model.
AB  - Suicide in older people is a significant public health issue given the aging
      population and increasing suicide rates with age in many parts of the world.
      Depression and physical illness are two factors consistently associated with
      suicidal behavior in older people; however, their inter-relationships are not
      well understood. We present here a case study based on a newly developed
      conceptual model illustrating the various medical, psychological, social and
      resilience factors involved in the progression of physical illness to suicidal
      behavior. This model provides a framework for clinicians to understand protective
      factors and address late-life suicide risk.

PMID- 28452675
TI  - Subjective Age and Dementia.
AB  - OBJECTIVE: Existing evidence indicates that a younger subjective age is a marker
      of successful aging, including better health and cognition. Building upon this
      evidence, it is likely that individuals with dementia might feel older. However,
      subjective evaluation of age might not be affected by dementia because these
      individuals tend to be anosognosic and report positive health-related quality of
      life. METHODS: Data from two cross-sectional samples from France and the United
      States were used to compare the subjective age ratings of individuals with and
      without dementia. RESULTS: Results from both samples revealed that individuals
      with dementia felt younger than their age but did not differ from the controls,
      even after controlling for sex, chronological age, education, and self-rated
      health. CONCLUSION: The present study suggests that there are no large
      differences in the subjective experience of age between healthy individuals and
      those with dementia.

PMID- 28452676
TI  - Telephone-Delivered Cognitive-Behavioral Therapy for Older, Rural Veterans with
      Depression and Anxiety in Home-Based Primary Care.
AB  - OBJECTIVES: Rural, homebound older adults are at increased risk for anxiety and
      depression and have limited access to mental health services. These individuals
      face many barriers to receiving evidence-based mental health treatment and would
      benefit from interventions that increase access to and efficiency of care. The
      aim of this study was to evaluate use of a telephone-delivered, modular,
      cognitive behavioral therapy (CBT) intervention for both late-life depression and
      anxiety delivered to rural, homebound Veterans. METHODS: Three cases are
      presented to illustrate the flexible adaptation of the intervention for use among
      older Veterans enrolled in home-based primary care, with varying symptom
      presentations and functional limitations. The Veterans received 7 to 9 sessions
      of the CBT intervention, with ordering of skill modules based on symptom
      presentation and determined collaboratively between patient and therapist.
      RESULTS: The three Veterans showed improvement in depression and/or anxiety
      symptoms following treatment and provided positive feedback regarding their
      experiences in this program. CONCLUSIONS: These results suggest that telephone
      delivered CBT is acceptable to older adults and can be tailored to individual
      patient needs. CLINICAL IMPLICATIONS: Clinicians should consider telephone
      delivered CBT as an alternate mode of therapy to increase access to mental health
      care for rural, homebound individuals with depression and anxiety.

PMID- 28452678
TI  - A new treatment for frostbite sequelae; Botulinum toxin.
AB  - Frostbite sequelae are a relevant occupational injury outcome for soldiers in
      arctic environments. A Caucasian male soldier suffered frostbite to both hands
      during a military winter exercise. He developed sensory-motor disturbances and
      cold hypersensitivity. Angiography and thermography revealed impaired blood flow
      while Quantitative Sensory Testing indicated impaired somato-sensory nerve
      function. Two years after the initial event, he received an off label treatment
      with Botulinum toxin distributed around the neurovascular bundles of each finger.
      After treatment, cold sensitivity was reduced while blood flow and somato-sensory
      nerve function improved. The successful treatment enabled the soldier to
      successfully pursue his career in the army.

PMID- 28452679
TI  - Yoik experiences and possible positive health outcomes: an explorative pilot
      study.
AB  - BACKGROUND: Yoik is an old vocal music tradition of Sami, the indigenous people
      inhabiting Northern Fennoscandia and Kola peninsula in Russia. Studies of music
      therapy (MT) and especially singing have documented improvements in social and
      overall functioning in people with severe mental disorders and positive effect on
      depressive symptoms and sleep quality. Possible connections between yoik and
      health are so far underexplored. OBJECTIVES: The overall aim of this study was to
      explore whether yoik may have the potential to positively influence people's
      health and well-being. The research questions were: 1. What are different
      persons' experiences with yoik? 2. Can yoik experiences be related to health
      outcomes? METHODS: Explorative, qualitative interviews with 13 participants were
      conducted in the Norwegian counties Finnmark, Troms, Nordland, and Trondelag.
      FINDINGS: The findings suggest qualities in yoik that are comparable to positive
      effects of Music Therapy (MT) in general. Yoik may contribute to emotion
      management, i.e. processing negative emotions and inducing positive ones in
      people acknowledging yoik as something positive. CONCLUSION: Yoik may be
      considered an important marker of social and cultural belonging for many Sami
      people. Yoik seems to have an underresearched potential as an intervention in
      culture sensitive healthcare and health promotion work that deserves to be
      further investigated.

PMID- 28452680
TI  - Contemporary radiooncological management of bone metastases from breast cancer:
      factors associated with prescription of different fractionation regimens (short
      or long course) in a rural part of North Norway with long travel distance.
AB  - The aim of this study was to reduce barriers that prevent implementation of
      evidence-based recommendations about single-fraction palliative radiotherapy
      (PRT) and to demonstrate that single-fraction PRT yields similar outcomes as long
      course treatment (>=10 fractions) in patients with bone metastases from breast
      cancer. This retrospective study (2007-2014) included 118 Norwegian female
      patients. All patients received guideline-conform systemic therapy including bone
      targeting agents. Median survival was 12.7 months. Long-course PRT was prescribed
      in 60% of patients, while 21% had PRT with a single fraction of 8 Gy to at least
      one target. Reirradiation rate was not significantly higher after 8 Gy (9%,
      compared to 5% after long-course PRT and 6% after 4 Gy x5). Patients with
      favorable baseline characteristics such as younger age and good performance
      status (PS) were significantly more likely to receive long-course PRT. Biological
      subtype and comorbidity did not correlate with fractionation. Prognosis was
      influenced by biological subtype, extra-skeletal disease extent, severe anemia
      and abnormal CRP. The limited need for reirradiation after single fraction PRT
      might encourage physicians to prescribe this convenient regimen, which would
      improve resource utilization. Even patients with PS3 had a median survival of 3
      months, which indicates that they could experience worthwhile clinical benefit.

PMID- 28452681
TI  - The effect of vernal solar UV radiation on serum 25-hydroxyvitamin D
      concentration depends on the baseline level: observations from a high latitude in
      Finland.
AB  - Humans obtain vitamin D from conversion of 7-dehydrocholesterol in the skin by
      ultraviolet B (UVB) radiation or from dietary sources. As the radiation level is
      insufficient in winter, vitamin D deficiency is common at higher latitudes. We
      assessed whether vernal solar UVB radiation at latitudes 61 degrees N and 67
      degrees N in Finland has an impact on serum 25-hydroxyvitamin D [S-25(OH)D]
      concentrations. Twenty-seven healthy volunteers participated in outdoor
      activities in snow-covered terrain for 4-10 days in March or April, with their
      face and hands sun-exposed. The personal UVB doses and S-25(OH)D levels were
      monitored. A mean UVB dose of 11.8 standard erythema doses (SED) was received
      during an average of 12.3 outdoor hours. The mean S-25(OH)D concentration in
      subjects with a baseline concentration below 90.0 nmol/L (n=13) increased
      significantly, by 6.0 nmol/L from an initial mean of 62.4 nmol/L (p<0.001),
      whereas in those with a basal concentration above 90.0 nmol/L (n=12) it decreased
      significantly, by 6.7 nmol/L from a mean of 116.9 nmol/L (p<0.01). To conclude,
      only 7% of total body surface area was exposed to vernal sunlight and this was
      capable of increasing S-25(OH)D levels in subjects with a baseline level below 90
      nmol/L but not in those with higher levels.

PMID- 28452682
TI  - Entamoeba histolytica: Host parasite interactions at the colonic epithelium.
AB  - Entamoeba histolytica (Eh) is the protozoan parasite responsible for intestinal
      amebiasis and interacts dynamically with the host intestinal epithelium during
      disease pathogenesis. A multifaceted pathogenesis profile accounts for why 90% of
      individuals infected with Eh are largely asymptomatic. For 100 millions
      individuals that are infected each year, key interactions within the intestinal
      mucosa dictate disease susceptibility. The ability for Eh to induce amebic
      colitis and disseminate into extraintestinal organs depends on the parasite
      competing with indigenous bacteria and overcoming the mucus barrier, binding to
      host cells inducing their cell death, invasion through the mucosa and outsmarting
      the immune system. In this review we summarize how Eh interacts with the
      intestinal epithelium and subverts host defense mechanisms in disease
      pathogenesis.

PMID- 28452683
TI  - Mechanisms and pathways of Toxoplasma gondii transepithelial migration.
AB  - Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic
      pathogen. Infection of the host occurs principally through oral consumption of
      contaminated food and water with the gastrointestinal tract being the primary
      route for entry into the host. To promote infection, T. gondii has evolved highly
      specialized strategies for rapid traversal of the single cell thick intestinal
      epithelial barrier. Parasite transmigration via the paracellular pathway between
      adjacent cells enables parasite dissemination to secondary sites of infection
      where chronic infection of muscle and brain tissue is established. It has
      recently been proposed that parasite interactions with the integral tight
      junction (TJ) protein occludin influences parasite transmigration of the
      intestinal epithelium. We review here the emerging mechanisms of T. gondii
      transmigration of the small intestinal epithelium alongside the developing role
      played in modulating the wider TJ-associated proteome to rewire host cell
      regulatory systems for the benefit of the parasite.

PMID- 28452684
TI  - Dynamic interactions of Plasmodium spp. with vascular endothelium.
AB  - Plasmodial species are protozoan parasites that infect erythrocytes. As such,
      they are in close contact with microvascular endothelium for most of the life
      cycle in the mammalian host. The host-parasite interactions of this stage of the
      infection are responsible for the clinical manifestations of the disease that
      range from a mild febrile illness to severe and frequently fatal syndromes such
      as cerebral malaria and multi-organ failure. Plasmodium falciparum, the causative
      agent of the most severe form of malaria, is particularly predisposed to
      modulating endothelial function through either direct adhesion to endothelial
      receptor molecules, or by releasing potent host and parasite products that can
      stimulate endothelial activation and/or disrupt barrier function. In this review,
      we provide a critical analysis of the current clinical and laboratory evidence
      for endothelial dysfunction during severe P. falciparum malaria. Future
      investigations using state-of-the-art technologies such as mass cytometry and
      organs-on-chips to further delineate parasite-endothelial cell interactions are
      also discussed.

PMID- 28452687
TI  - Exposures Associated with Minority High Schoolers' Predisposition for Health
      Science.
AB  - OBJECTIVE: We examined modifiable facilitation strategies (exposures) during high
      school that are associated with motiva- tion for minority youth pursuit of health
      science. METHODS: A sample (N = 116) of minority (73% African-American/Black, 21%
      Hispanic/Latino) 12th graders from 6 high schools in a lower socioeconomic area
      bordering Washington, DC completed a self-administered survey. Path modeling was
      used to examine whether: (1) exposures: high school science courses, extra
      curricular science activities, personal health experiences, and adult
      encouragement predict Theory of Planned Behavior (TPB) constructs including
      attitude, subjective norm, and perceived behavioral control, and (2) TPB
      constructs predict the outcome of intent to pursue college health science.
      RESULTS: The path model indicated that adult encouragement was associated with
      attitude (p < .01), subjective norm (p < .01), and perceived behavioral control
      (p < .01); and personal health experiences were associated with attitude (p <
      .01). Attitude and subjective norm were associated with intent (p < .01).
      CONCLUSION: Motivating minority high schoolers from low socioeconomic areas
      through adult encouragement and personal health experiences to value health
      scientists and to perceive that others support their pursuit of health science
      may be pathways for facilitating their intention to pursue college health
      science.

PMID- 28452685
TI  - Interactions of Giardia sp. with the intestinal barrier: Epithelium, mucus, and
      microbiota.
AB  - Understanding how intestinal enteropathogens cause acute and chronic alterations
      has direct animal and human health perspectives. Significant advances have been
      made on this field by studies focusing on the dynamic crosstalk between the
      intestinal protozoan parasite model Giardia duodenalis and the host intestinal
      mucosa. The concept of intestinal barrier function is of the highest importance
      in the context of many gastrointestinal diseases such as infectious enteritis,
      inflammatory bowel disease, and post-infectious gastrointestinal disorders. This
      crucial function relies on 3 biotic and abiotic components, first the commensal
      microbiota organized as a biofilm, then an overlaying mucus layer, and finally
      the tightly structured intestinal epithelium. Herein we review multiple
      strategies used by Giardia parasite to circumvent these 3 components. We will
      summarize what is known and discuss preliminary observations suggesting how such
      enteropathogen directly and/ or indirectly impairs commensal microbiota biofilm
      architecture, disrupts mucus layer and damages host epithelium physiology and
      survival.

PMID- 28452688
TI  - Ethno-cultural Preferences in Receipt of Heart Health Information.
AB  - OBJECTIVE: We attempted to understand how people of South Asian and Chinese
      descent prefer to receive health information. METHODS: To achieve this end we
      conducted a search of academic and grey literature articles published between
      1946 and 2016. To be included, articles had to be focused South Asian and Chinese
      specific ethno-culturally-based preferences of receiving health information.
      RESULTS: A total of 3478 abstracts were retrieved, of which, 27 articles met the
      inclusion criteria. We were able to identify South Asian and Chinese people's
      preferences for and facilitators of receiving health information. South Asians
      and Chinese preferred health information and programs that were more culturally
      relevant and appealing, had translations into South Asian and Chinese languages,
      and used simple terms as opposed to technical jargon. CONCLUSIONS: There is
      little direction regarding for how to tai- lor health information South Asian and
      Chinese ethno-cultural groups. Having evidence-based information about how South
      Asians and Chinese prefer to receive health information has potential to enhance
      patients' learning and health literacy, improve clinical outcomes, and reduce
      health disparities.

PMID- 28452686
TI  - Helminths and intestinal barrier function.
AB  - Approximately one-sixth of the worlds' population is infected with helminths and
      this class of parasite takes a major toll on domestic livestock. The majority of
      species of parasitic helminth that infect mammals live in the gut (the only niche
      for tapeworms) where they contact the hosts' epithelial cells. Here, the helminth
      intestinal epithelial interface is reviewed in terms of the impact on, and
      regulation of epithelial barrier function, both intrinsic (epithelial
      permeability) and extrinsic (mucin, bacterial peptides, commensal bacteria)
      elements of the barrier. The data available on direct effects of helminths on
      epithelial permeability are scant, fragmentary and pales in comparison with
      knowledge of mobilization of immune reactions and effector cells in response to
      helminth parasites and how these impact intestinal barrier function. The
      interaction of helminth-host and helminth-host-bacteria is an important
      determinant of gut form and function and precisely defining these interactions
      will radically alter our understanding of normal gut physiology and
      pathophysiological reactions, revealing new approaches to infection with
      parasitic helminths, bacterial pathogens and idiopathic auto-inflammatory
      disease.

PMID- 28452689
TI  - Assessing the Network of Agencies in Local Communities that Promote Healthy
      Eating and Lifestyles among Populations with Limited Resources.
AB  - OBJECTIVES: We assessed the network of agencies in local communities that promote
      healthy eating and lifestyles among populations with limited resources. METHODS:
      Network surveys were administered among 159 Illinois agencies identified as
      serving limited-resource audiences categorized into 8 types: K-12 schools, early
      childhood centers, emergency food providers, health-related agencies, social
      resource centers, low-income/subsidized housing complexes, continuing education
      organizations, and others. Network analysis was conducted to examine 4 network
      structures - communications, funding, cooperation, and collaboration networks
      between agencies within each county/county cluster. RESULTS: Agencies in a
      network were found to be loosely connected, indicated by low network density.
      Reporting accuracy might be of concern, indicated by low reciprocity. Agencies in
      a network are decentralized rather than centralized around a few influential
      agencies, indicated by low betweenness centrality. There is suggestive evidence
      regarding homophily in a network, indicated by some significant correlations
      within agencies of the same type. Agencies connected in one network are
      significantly more likely to be connected in all the other networks as well.
      CONCLUSIONS: Promoting healthy eating and lifestyles among populations with
      limited resources warrants strong partnership across agencies in communities.
      Network analysis serves as a useful tool to evaluate community partnerships and
      facilitate coalition building..

PMID- 28452690
TI  - Patterns of 'Abnormal' Illness Behavior among Healthy Individuals.
AB  - OBJECTIVES: We extend the seminal work of Professor Issy Pilowsky by presenting a
      contemporary re-conceptualization of abnormal illness behavior (AIB) as a general
      psychological phenomenon evident among healthy community members. METHODS:
      Participants (N = 344) completed a self- report questionnaire comprising health
      information and well-validated psychological measures from the field of
      somatization (eg, AIB, attributional style for physical symptoms, cognitive
      distortion of somatic information, illness likelihood, maladaptive coping).
      RESULTS: Cluster analysis of illness behavior responses resulted in 3 unique
      groupings distinguished by key health and psychological variables. Cluster 1
      reflected 'normal' responses, Cluster 2 'atypical' and Cluster 3 'maladaptive'.
      Cluster 3 may represent a personality attribute indicative of a general style of
      interpreting illness in a more extreme way (trait AIB) whereas Cluster 2 may
      reflect a transient response to a specific illness event (state AIB).
      CONCLUSIONS: The construct of 'abnormal' illness behavior may usefully be
      extended to include individual differences in responses regardless of current
      health status. Furthermore, the potential to further characterize illness
      behavior as either dispositional (trait) or situational (state) emerges as a
      fruitful area for future analyses. Specifically, longitudinal studies are
      recommended to determine the causal links between health events and illness
      behavior profiles.

PMID- 28452691
TI  - The Theory of Planned Behavior as a Predictor of HIV Testing Intention.
AB  - OBJECTIVES: This investigation tests the theory of planned behavior (TPB) as a
      predictor of HIV testing intention among Nigerian university undergraduate
      students. METHODS: A cross-sectional study of 392 students was conducted using a
      self-administered structured questionnaire that measured socio-demographics,
      perceived risk of human immunodeficiency virus (HIV) infection, and TPB
      constructs. Analysis was based on 273 students who had never been tested for HIV.
      Hierarchical multiple regression analysis assessed the applicability of the TPB
      in predicting HIV testing intention and additional predictive value of perceived
      risk of HIV infection. RESULTS: The prediction model containing TPB constructs
      explained 35% of the variance in HIV testing intention, with attitude and
      perceived behavioral control making significant and unique contributions to
      intention. Perceived risk of HIV infection contributed marginally (2%) but
      significantly to the final prediction model. CONCLUSIONS: Findings supported the
      TPB in predicting HIV testing intention. Although future studies must determine
      the generalizability of these results, the findings highlight the importance of
      perceived behavioral control, attitude, and perceived risk of HIV infection in
      the prediction of HIV testing intention among students who have not previously
      tested for HIV.

PMID- 28452692
TI  - A Cash-back Rebate Program for Healthy Food Purchases in South Africa: Selection
      and Program Effects in Self-reported Diet Patterns.
AB  - OBJECTIVES: A South African insurer launched a rebate program for healthy food
      purchases for its members, but only available in program-designated supermarkets.
      To eliminate selection bias in program enrollment, we estimated the impact of
      subsidies in nudging the population towards a healthier diet using an
      instrumental variable approach. METHODS: Data came from a health behavior
      questionnaire administered among members in the health promotion program.
      Individual and supermarket addresses were geocoded and differential distances
      from home to program-designated supermarkets versus competing supermarkets were
      calculated. Bivariate probit and linear instrumental variable models were
      performed to control for likely unobserved selection biases, employing
      differential distances as a predictor of program enrollment. RESULTS: For regular
      fast-food, processed meat, and salty food consumption, approximately two-thirds
      of the difference between participants and nonparticipants was attributable to
      the intervention and one-third to selection effects. For fruit/ vegetable and
      fried food consumption, merely one-eighth of the difference was selection. The
      rebate reduced regular consumption of fast food by 15% and foods high in
      salt/sugar and fried foods by 22%- 26%, and increased fruit/vegetable consumption
      by 21% (0.66 serving/day). CONCLUSIONS: Large population interventions are an
      essential complement to laboratory experiments, but selection biases require
      explicit attention in evaluation studies conducted in naturalistic settings.

PMID- 28452693
TI  - South Korean Adolescents' Intention to Smoke.
AB  - OBJECTIVES: The purpose of this study was to examine associations between
      intention to smoke, and 3 constructs of the Theory of Planed Behavior, including
      attitude, subjective norm, and perceived behavioral control related to smoking
      among adolescents in South Korea. METHODS: We used a cross-sectional
      correlational design. The survey was conducted on 13- to 15-year-old adolescents
      (N = 740) in Seoul, South Korea. Multilevel modeling was conducted to analyze the
      data. RESULTS: After adjusting for socio-demographic and economic factors,
      attitude toward smoking, subjective norm about smoking, and perceived behavioral
      control about smoking were independent statistically significant predictors of in
      tention to smoke. When all 3 were considered together, attitude toward smoking
      and perceived behavioral control remained statistically significant, but
      subjective norm about smoking did not. The number of licensed tobacco retailers
      also predicted intention to smoke. CONCLUSIONS: Attitude, perceived behavioral
      control, and tobacco retailers around schools need to be considered when
      developing tobacco prevention and control programs and policies for adolescents.

PMID- 28452694
TI  - Diet and Physical Activity in African-American Girls: Seasonal Differences.
AB  - OBJECTIVE: Diet and physical activity (PA) may vary by season. METHODS: Two 24
      hour dietary recalls and 7 days of accelerometry were collected from 342 8-10
      year-old African-American girls between January 2013 and October 2014. Season was
      based on time of data collection (fall, spring, winter, summer). Seasonal
      differences in diet and PA were assessed. RESULTS: Mean age was 8.9 years; 53%
      were low income. Girls with summer baseline data collection reported consuming
      significantly less 100% fruit juice than those with winter and spring data.
      Summer dairy consumption was significantly lower than the other 3 seasons for low
      income girls. Significantly more desserts were consumed during winter than in
      spring or summer. Significantly more sugar-sweetened beverages (SSBs) were
      consumed during spring and summer for all girls than in the fall. Steps per day
      for all girls and the low-income girls were significantly lower in summer
      compared to the other seasons. CONCLUSIONS: Higher consumption SSBs and lower
      steps per day during the summer are a concern, particulary for African-American
      girls at high risk for obesity. Interventions to address these seasonal
      differences should be initiated.

PMID- 28452695
TI  - Sport Participation and Academic Achievement: A Longitudinal Study.
AB  - OBJECTIVES: We examined the relation- ship between sport participation and
      academic achievement in a sample of adolescents, while accounting for
      socioeconomic status (SES) and sex. METHODS: We analyzed data from a cohort of
      271 Mid-Atlantic high school students who participated in a longitudinal study of
      risk and protective factors for substance use, teen parenting, and school drop
      out. RESULTS: Sport participation at year one predicted academic achievement in
      English (p < .05) and mathematics (p < .05) at year 2, while controlling for
      academic achievement at year one. In both instances over other independent
      variables and covariates in the models, sport participation explains almost 7% of
      additional variance in the outcomes variables. We also found a positive
      relationship for participants who reported parents with some college experience
      as opposed to parents with no college experience, between sport participation and
      grades in English (p < .05) but not for mathematics. CONCLUSIONS: Sport
      participation is positively related to academic achievement but the relationship
      diverges when students are compared across sex and by parental education. These
      findings suggest that the relation ship between sport participation and academic
      achievement may be influenced by SES and is related to sex.

PMID- 28452696
TI  - Personal and Environmental Resources Mediate the Positivity-Emotional Dysfunction
      Relationship.
AB  - OBJECTIVES: We investigated the relationships among positivity, perceived
      personal and environmental resources, and emotional dysfunction in adolescent
      girls. We hypothesized that perceived resources would mediate the relationship
      between positivity and emotional dysfunction. METHODS: Participants (N = 510)
      attending an all-girls public school completed a survey assessing emotional
      dysfunction (depressive symptoms and perceived stress), positivity
      (positive/negative emotions), and personal/ environmental resources (resilience,
      hope, percent adaptive coping, community connectedness, social support, and
      school connectedness). Perceived resources were combined into one latent
      variable, and structural equation modeling tested the mediating effect of
      perceived resources on the relationship between positivity and emotional
      dysfunction. RESULTS: The model accounted for 63% of the variance in emotional
      dysfunction. Positivity exerted a significant direct effect on emotional
      dysfunction (beta = -.14, p < .01), but its influence was primarily mediated
      through perceived resources (indirect effect: beta = -.43, p < .001).
      CONCLUSIONS: The impact of positivity on emotional dysfunction is primarily but
      not entirely mediated by perceived personal and environmental resources. Schools
      should consider strategies to enhance experiences of positive emotions and/or
      decrease experiences of negative emotions, in conjunction with encouraging
      student awareness and development of personal and environmental resources.

PMID- 28452697
TI  - A Content Analysis of Unique Selling Propositions of Tobacco Print Ads.
AB  - OBJECTIVES: We describe the unique selling propositions (USPs) (propositions used
      to convince customers to use a particular brand/product by focusing on the unique
      benefit) of print tobacco ads. METHODS: A qualitative content analysis was
      conducted of print tobacco ads (N = 171) selected from August 2012 to August 2013
      for cigarettes, moist snuff, e-cigarettes, cigars, and snus to determine the
      content and themes of USPs for tobacco ads. RESULTS: Cigarette ad USP themes
      focused on portraying the product as attractive; moist snuff ads focused on
      portraying product as masculine; cigar ads focused on selling a "high end
      product;" and new and emerging tobacco products (e-cigarette, snus) focused on
      directly comparing these products to cigarettes. CONCLUSIONS: Whereas traditional
      tobacco product ads used USPs focused on themes of enjoyment and pleasure (eg,
      attractive for cigarettes, "high end product" for cigars), new and emerging
      tobacco product ads offered the unique benefit (USP) of their product being a
      better and "safer" alternative to traditional tobacco products. Snuff's USPs
      focused nearly exclusively on the masculinity of their products. Our results
      provide targets for potential tobacco regulatory actions that could be
      implemented to reduce demand for tobacco products by reducing their perceived
      unique benefits.

PMID- 28452699
TI  - Health Literacy among Iranian High School Students.
AB  - OBJECTIVE: We examined the health lit- eracy status of high school students in
      Kerman, Iran. METHODS: This descriptive cross-sectional study was conducted at
      high schools in Kerman. Data concerning 3 dimensions of health literacy (health
      knowledge, health skills and health be- haviors) were collected from 312 students
      using an adapted version of a valid and reliable questionnaire developed by the
      Ministry of Health of China. Data analysis was performed by descriptive
      statistics and chi-square analysis using SPSS version 22. RESULTS: The average
      age of the students was 16 +/- 3 years and 50% (N = 156) of them were girls.
      Twenty-nine percent of students gained a health literacy score between 37 and 47
      (adequate). A statistically significant relationship was found between health
      literacy and type of school (p < .004), family income (p < .03), and parents'
      education level (p < .001). CONCLUSION: A large percentage of adolescents in Iran
      have inadequate health literacy requiring serious interventions by authorities
      and policy-makers. Incorporating subjects such as mental health, prevention of
      addiction, and puberty and sexual health into educational curricula can improve
      Iranian students' health literacy.

PMID- 28452698
TI  - Hepatitis B Screening & Vaccination Behaviors in a Community-based Sample of
      Chinese & Korean Americans in New York City.
AB  - OBJECTIVES: As Asian Americans are dis- proportionately affected by the hepatitis
      B virus (HBV), we explored predictors of HBV screening and vaccination among
      Chinese and Korean Americans. METHODS: We used cross-sectional data from a com-
      munity-based sample of Chinese Americans (N = 502) and Korean Americans (N = 487)
      residing in the metropolitan New York City area during 2008-2009. Logistic
      regression models were stratified by Asian-American subgroup and sex to predict
      HBV screening (for the entire sam- ple) and HBV vaccination (among those not HBV
      positive). RESULTS: Overall, screening rates were high (71.3% among Chinese and
      70.1% among Koreans). The majority of respondents were aware of HBV; however,
      knowledge about HBV transmission was low. In logistic regression, a physician
      recommendation was consistently associated with HBV screening and vaccination
      outcomes across all groups; having heard of HBV was significantly associated with
      screening and vaccination among Chinese males and screening among Korean males
      and females. Screening and vaccination barriers were reported among all groups,
      and included lack of knowledge and feeling well/having no health issues.
      CONCLUSIONS: Targeted efforts in these at-risk communities are necessary to
      improve HBV knowledge, address misinformation about HBV, and eliminate provider-,
      patient-, and resource-related barriers to HBV screening and vaccination.

PMID- 28452700
TI  - Presentation, workup, and management of penetrating transorbital and transnasal
      injuries: A case report and systematic review.
AB  - BACKGROUND: A foreign body (FB) penetrating intracranially after passing
      transorbitally or transnasally is a rare occurrence. However, otolaryngologists
      are increasingly being asked to participate in the care of these patients for
      both endoscopic removal of the object and repair of any skull base defects.
      OBJECTIVE: To assess the presentation, workup, and management of transnasal or
      transorbital penetrating FB injury. METHODS: Systematic review of the
      presentation, workup, and management of transnasal or transorbital penetrating FB
      injury; plus, a case report of a 53-year-old woman with a transorbital
      penetrating rose bush branch. We searched medical literature data bases, which
      resulted in 215 total titles, which were then narrowed based on inclusion and
      exclusion criteria. RESULTS: Thirty-five cases of transorbital or transnasal low
      velocity trauma that involved the paranasal sinuses were reviewed from 33
      articles. The average age was 30 years, 40% of the objects were made of wood.
      Fifty-seven percent of the cases were transorbital, whereas 43% were transnasal.
      Forty-six percent of the surgical interventions were completed endoscopically or
      with endoscopic assistance. Complications of injury were common, with 66% of
      patients experiencing cerebrospinal fluid leaks; 23%, permanent blindness; 17%,
      meningitis; 14%, ophthalmoplegia; 9%, decreased visual acuity; and 3%, brain
      abscess. Our patient presented with a traumatic cerebrospinal fluid leak, and
      recovered well after transorbital and endoscopic removal of the branch, skull
      base repair, and a prolonged course of antibiotics and antifungal medications.
      CONCLUSIONS: Transnasal and transorbital penetrating FB injuries are a relatively
      uncommon occurrence but when they do occur require rapid workup and
      interdisciplinary management to prevent acute and delayed complications.

PMID- 28452702
TI  - Effect of doxycycline on epithelial-mesenchymal transition via the p38/Smad
      pathway in respiratory epithelial cells.
AB  - PURPOSE: Doxycycline has antibacterial and anti-inflammatory effects, and it also
      suppresses collagen biosynthesis. This study aimed to confirm the effects and
      mechanism of doxycycline on transforming growth factor (TGF) beta 1 induced
      epithelial-mesenchymal transition and cell migration in A549 and primary nasal
      epithelial cells. METHODS: A 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium
      bromide assay and phalloidin-fluorescein isothiocyanate staining were used to
      evaluate cytotoxicity and cellular morphologic changes. Western blot and
      immunofluorescence staining were used to determine the expression levels of E
      cadherin, vimentin, alpha-smooth muscle actin, fibronectin, phosphorylated
      Smad2/3, and mitogen-activated protein kinases. Scratch and transwell migration
      assays were used to assess cellular migration ability. RESULTS: Doxycycline (0-10
      MUg/mL) had no significant cytotoxic effects in A549 and primary nasal epithelial
      cells. Increased expression of mesenchymal markers, including vimentin, alpha
      smooth muscle actin, and fibronectin in TGF beta 1 induced A549 cells were
      downregulated by doxycycline treatment. In contrast, E-cadherin expression was
      upregulated in TGF beta 1 induced A549 cells. An in vitro cell migration assay
      showed that doxycycline also inhibited the ability of TGF beta 1 induced
      migration. Doxycycline treatment suppressed the activation of Smad2/3 and p38,
      whereas its inhibitory effects were similar to each element-specific inhibitor in
      A549 and primary nasal epithelial cells. CONCLUSION: Doxycycline inhibited TGF
      beta 1 induced epithelial-to-mesenchymal transition and migration by targeting
      Smad2/3 and p38 signal pathways in respiratory epithelial cells.

PMID- 28452703
TI  - Cigarette smoke extract increases vascular endothelial growth factor production
      via TLR4/ROS/MAPKs/NF-kappaB pathway in nasal fibroblast.
AB  - PURPOSE: Cigarette smoke is a complex mixture of various chemical compounds,
      including free radicals and highly toxic compounds. Cigarette smoke exposure has
      been shown to be associated with chronic rhinosinusitis and tissue remodeling in
      upper airway. Vascular endothelial growth factor (VEGF) is one of the cytokines
      with a crucial role in tissue remodeling of airway. The aims of this study were
      to determine the effects of cigarette smoke extract (CSE) on VEGF expression and
      to investigate the underlying molecular mechanisms of CSE in nasal fibroblasts.
      METHODS: Nasal fibroblasts were stimulated with CSE. Cytotoxicity was evaluated
      by 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. The
      expression level of VEGF was measured using reverse transcription-polymerase
      chain reaction (RT-PCR), and enzyme-linked immunosorbent assay. Messenger RNA
      (mRNA) expression level of TLR4 were determined by RT-PCR. Small interfering RNA
      (siRNA) for TLR4 was transfected to suppress TLR4 expression. Activation of
      reactive oxygen species (ROS) was analyzed by using dichloro-dihydro-fluorescein
      diacetate assay. Mitogen-activated protein kinase (MAPK) and NF-kappaB
      activations were determined by using western blot and/or luciferase assay.
      RESULTS: CSE had no significant cytotoxic effect in nasal fibroblast up to 5%.
      CSE significantly increased both VEGF mRNA and protein expression dose
      dependently. The down-regulation of TLR4 transcription by siRNA treatment
      suppressed CSE-induced expressions of both TLR4 and VEGF. Pretreatment with ROS
      scavengers, specific inhibitors of each MAPK, and NF-kappaB inhibitor
      significantly decreased CSE-induced VEGF expression. CONCLUSIONS: CSE has a
      stimulatory effect on VEGF expression through the TLR4, ROS, MAPK, and NF-kappaB
      signaling pathway in nasal fibroblasts.

PMID- 28452704
TI  - Nitric oxide production is stimulated by bitter taste receptors ubiquitously
      expressed in the sinonasal cavity.
AB  - BACKGROUND: Bitter taste receptors (T2R) have recently been demonstrated to
      contribute to sinonasal innate immunity. One T2R, T2R38, regulates mucosal
      defense against gram-negative organisms through nitric oxide (NO) production,
      which enhances mucociliary clearance and directly kills bacteria. To determine
      whether additional T2Rs contribute to this innate defense, we evaluated two other
      sinonasal T2Rs (T2R4 and T2R16) for regulation of NO production and expression
      within the human sinonasal cavity. METHODS: Primary human sinonasal cultures were
      stimulated with ligands specific to T2R4 and T2R16, colchicine and D-salicin,
      respectively. Cellular NO production was measured by intracellular 4-amino-5
      methylamino-2',7'-difluorofluorescein diacetate fluorescence. For T2R expression
      mapping, sinonasal tissue was obtained from patients who underwent sinus surgery
      of the middle turbinate, maxillary sinus, ethmoid sinus, or sphenoid sinus. The
      expression of T2R4, T2R16, and T2R38 was evaluated by using immunofluorescence
      with validated antibodies. RESULTS: Similar to T2R38, T2R4 and T2R16 trigger NO
      production in a dose-dependent manner by using the canonical taste signaling
      pathway in response to stimulation with their respective ligands. All three
      receptors were expressed in the cilia of human epithelial cells of all regions in
      the sinonasal cavity. CONCLUSION: These three T2Rs signaled through the same NO
      mediated antimicrobial pathway and were ubiquitously expressed in the sinonasal
      epithelium. Additional T2Rs besides T2R38 may play a role in sinonasal immune
      defense. Mapping of T2R expression demonstrated the potential widespread role of
      T2Rs in sinonasal defense, whereas the genetics of these T2Rs may contribute to
      our understanding of specific endotypes of chronic rhinosinusitis and develop
      into novel therapeutic targets.

PMID- 28452705
TI  - Normal saline solution nasal-pharyngeal irrigation improves chronic cough
      associated with allergic rhinitis.
AB  - BACKGROUND: Upper airway inflammation is one of the most commonly identified
      causes of chronic cough, although the underlying mechanism is not clear. This
      study compared normal saline solution nasal-pharyngeal irrigation (NSNPI) and
      fluticasone propionate nasal spray (FPNS) treatment for chronic cough associated
      with allergic rhinitis (AR). METHODS: Patients with suspected AR to house-dust
      mite were enrolled, and the symptom of cough was assessed by a cough symptom
      score and the Leicester Cough Questionnaire, and cough response to capsaicin was
      evaluated. AR was assessed by using the visual analog scale (VAS) and the Mini
      Juniper Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Mediators,
      including histamine, leukotriene C4, and prostaglandin D2, and the major basic
      protein from nasal lavage fluid (NLF) were examined. The patients were treated
      with NSNPI (the NSNPI group) or FPNS (the FPNS group) for 30 days, after which
      they were reassessed. RESULTS: Forty-five of 50 patients completed this study.
      The scores of the cough symptom and the Leicester Cough Questionnaire, and the
      capsaicin cough threshold all improved statistically after NSNPI but did not
      change after FPNS. There were statistically significant changes in the
      evaluations of the MiniRQLQ and the mediators, including histamine and
      leukotriene C4, in the NLF in the NSNPI group. However, significant changes were
      found in the assessments of VAS, MiniRQLQ, and all above mediators including
      histamine, leukotriene C4, and prostaglandin D2, and the major basic protein in
      the NLF of the FPNS group. Furthermore, the assessments of VAS and all the
      mediators were reduced more in the FPNS group compared with those in the NSNPI
      group. CONCLUSION: The patients with suspected AR to house-dust mite reported a
      better relief of the cough symptom after 30 days of treatment with NSNPI compared
      with that after nasal corticosteroid.

PMID- 28452706
TI  - Respiratory viral detection in the paranasal sinuses of patients with cystic
      fibrosis.
AB  - BACKGROUND: Pulmonary colonization with antibiotic-resistant organisms in
      patients with cystic fibrosis (CF) is often preceded by upper-airway infections.
      Although there is a well-described relationship between pulmonary respiratory
      viral infections and overall disease progression of CF, the pathogenicity of
      respiratory viral infections in the paranasal sinuses of patients with CF remains
      unknown. With recent advances in respiratory virus detection techniques, this
      study sought to detect the presence of respiratory viruses in the paranasal
      sinuses of patients with CF in comparison with healthy controls and to correlate
      the viral presence with clinical measures of sinonasal disease. METHODS: This
      prospective individual cohort study compared 24 patients with CF with 14 healthy
      controls. Basic demographics, clinical measures of disease and respiratory viral
      screens (commercial multiplex) obtained directly from the paranasal sinuses were
      compared between the two groups. RESULTS: Respiratory viruses were detected in
      33% of patients with CF (8/24) compared with 0% of the healthy controls (0/14) (p
      = 0.017). Respiratory viruses were only detected during the winter months, and
      the most commonly identified were influenza A and human rhinovirus strains. There
      was no statistical difference in the 22-Item Sino-Nasal Outcome Test (SNOT-22)
      scores (p = 0.93) or modified Lund-Kennedy scores (p = 0.74) between patients
      with CF with a positive viral test and those without a positive result.
      CONCLUSIONS: Respiratory viral detection is more commonly detected in the
      paranasal sinuses of patients with CF compared with healthy controls. Although
      respiratory viral presence did not correlate with a worse clinical severity of
      sinonasal disease, these findings may provide insight into the pathophysiology of
      CF and open new avenues for potential targeted therapy.

PMID- 28452707
TI  - Complete surgical resection and short-term survival in acute invasive fungal
      rhinosinusitis.
AB  - BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a fulminant fungal
      infection seen in patients who are immunocompromised. Due to its rarity, there is
      little evidence regarding the appropriate antifungal treatment regimen,
      especially the degree of surgical intervention. OBJECTIVE: To assess factors that
      impact short-term survival in AIFR as defined by survival to hospital discharge
      and to develop a staging system to predict survival and complete surgical
      resection. METHODS: Fifty-four patients with histopathologically diagnosed AIFR
      who met inclusion criteria were identified between 1984 and 2014. Patient
      characteristics, disease extent, treatment modality, and short-term survival data
      were collected. Univariate analysis was performed to assess for factors
      associated with survival and increased likelihood of surgical resection. RESULTS:
      Of 52 patients with adequate documentation, 36 (69.2%) survived their hospital
      stay. Complete surgical resection was the only factor associated with improved
      survival (survival, 95.5%; p < 0.01). A surgical staging system was proposed to
      guide probability of complete resection and overall prognosis, with stage I
      disease limited to the nasal cavity, stage II involving the paranasal sinuses,
      stage III involving the orbit, and stage IV with skull base or intracranial
      extension. The chi2 analyses showed a decreased likelihood of complete surgical
      resection with stage III or IV disease compared with stage I (resection, 90.9%)
      (stage III resection, 37.5% [p = 0.01]; stage IV resection, 16.7% [p = 0.002]).
      There was a decreased likelihood of survival associated with increasing disease
      stage compared with stage I (survival, 100%) (stage II survival, 60% [p = 0.009];
      stage III survival, 62.5% [p = 0.02]; stage IV survival, 54.6%, [p = 0.006]).
      CONCLUSION: Although further studies are needed to define specific treatment
      protocols, analysis of these data indicated that endoscopic sinus surgery with
      the goal of complete surgical resection may provide the best survival outcomes in
      select patients when complete surgical resection can be performed. Our staging
      system represents the first attempt to predict surgical success and prognosis in
      patients with AIFR.

PMID- 28452708
TI  - Evolution of sinonasal symptoms and mucosal healing after minimally invasive
      pituitary surgery.
AB  - BACKGROUND: Minimally invasive pituitary surgery (MIPS) via endoscopy has become
      widely accepted as the surgical paradigm of choice for pituitary pathology. The
      objective of the current study was to analyze the evolution of symptom scores and
      mucosal healing after MIPS. METHODS: The 22-item Sino-Nasal Outcome Test (SNOT
      22) scores and objective endoscopic data of 52 patients were reviewed in a
      longitudinal manner. Scaled averages of the SNOT-22 and endoscopic scores from
      different time points were compared with baseline scores by using nonparametric
      testing. The time to baseline for endoscopic examinations was also analyzed by
      using Kaplan-Meier curves. RESULTS: The rhinologic symptoms subdomain of the SNOT
      22 scores showed statistically significant worsening between baseline and 2 weeks
      after surgery (p = 0.03). Follow-up SNOT-22 scores after 2 weeks showed no
      significant differences compared with baseline scores, with an overall trend
      toward improvement in patient symptoms during the subsequent period. Similar
      analysis for the endoscopic data illustrated statistically significant
      differences from the baseline scores up to 16 weeks after surgery. The overall
      trend showed a worsened endoscopic examination, initially with a spike at ~8 to
      10 weeks (p = 0.03) and with a subsequent return to baseline. The Kaplan-Meier
      estimate curve demonstrated a median time to return to baseline endoscopy at 18.9
      weeks (95% confidence interval, 14.9-38.3 weeks). CONCLUSION: The longitudinal
      data exhibited subjective improvement of patient outcomes based on SNOT-22 scores
      within 2-4 weeks after MIPS. However, the objective endoscopic data revealed a
      lag in improvement of the examination, typically at 16-20 weeks, which
      underscores ongoing careful endoscopic assessment and management to ensure proper
      mucosal healing beyond just subjective symptoms as the gauge to postoperative
      recovery.

PMID- 28452709
TI  - The use of polydioxanone plates for endoscopic skull base repair.
AB  - BACKGROUND: Many reconstructive techniques and materials have been reported for
      repair of skull base defects after sinonasal tumor excision, cerebrospinal fluid
      (CSF) leaks, and coverage of denuded bone. Synthetic materials have been
      developed for endoscopic skull base repair to avoid donor-site morbidity.
      Polydioxanone plate is a bioabsorbable implant designed for nasal septal
      reconstruction and has the ability to retain strength for at least 10 weeks and
      absorbs in 6 months. OBJECTIVES: This study aimed to describe the use of
      polydioxanone plates in endoscopic skull base defect and CSF leak repair, and to
      describe our experience with the surgical technique and postoperative management.
      METHODS: This was a retrospective case series of patients who, between May 2013
      and December 2015, underwent endoscopic sinus surgery and skull base repair for
      CSF leak or after excision of a skull base tumor by using polydioxanone plates.
      Patients who presented with sinonasal inflammatory disease or skull base tumors
      underwent endoscopic skull base repair by using polydioxanone plates in an
      underlay fashion and mucosal membrane grafts with or without adjuvant materials
      in an overlay fashion. The patients were reviewed at 6 days, 6 weeks, and 3
      months after surgery. Postoperative adverse events, including CSF leak,
      infection, bleeding, headache, and graft failure, were recorded. RESULTS: The
      cases of seven patients (five women, two men; mean age, 53.9 years) were
      reviewed. Five patients underwent sinonasal tumor resection and two underwent
      repair for CSF leak. The mean (standard deviation) defect size was 16.4 +/- 11.4
      mm. There was no evidence of postoperative CSF leak, and lumbar drains were not
      used. One patient reported transient headache and facial pressure at the 6-week
      follow-up visit. The surgeons' experience with polydioxanone plate placement,
      postoperative healing, and follow-up was satisfactory. CONCLUSION: Polydioxanone
      could be used to achieve rigid repair of endoscopic skull base defects. These
      early results, although promising, require validation in clinical trials.

PMID- 28452710
TI  - Excavating meningoencephaloceles: A newly recognized entity.
AB  - BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks are largely attributed to
      idiopathic intracranial hypertension and typically present as skull base defects
      with or without prolapse of intracranial contents. However, in our practice, we
      have encountered a distinct type of spontaneous CSF leak that presents in a
      different manner. OBJECTIVE: To discuss a newly-classified, difficult to treat,
      subset of spontaneous CSF leaks that present as excavation of the bone of the
      skull base in a tunnel- or canal-like fashion by a meningocele or
      meningoencephalocele instead of as a localized area of bony dehiscence. METHODS:
      A retrospective review was performed at a tertiary care rhinology practice to
      identify a subset of CSF leak patients with an excavating/canal-like skull base
      defect visualized radiographically on computed tomography (CT) scan or magnetic
      resonance imaging and/or endoscopically in the operating room. RESULTS: The
      cohort of patients consisted of 7 females and 1 male with an average age of 53.6
      years and a self-reported race of 4:3:1 African-American:Caucasian:Indian. All
      patients presented with CSF rhinorrhea. The most common leak site was the
      cribriform and upper septum. Six of the 8 patients had multiple defects and/or
      progression of their skull base defects, and 5 patients required multiple and/or
      repeat repairs in the operating room. Seven of the 8 patients underwent a
      cisternogram because the excavating nature of the leaks made it difficult to
      identify the specific leak site on high-resolution CT scan alone. CONCLUSION: In
      spontaneous CSF leaks that are difficult to identify or recur soon after a proper
      repair, an excavating pattern should be considered. Failure to recognize this
      type of leak and all of its tributaries, to fully unroof the excavated bone to
      completely resect the meningocele, and to visualize and close the site of origin
      will likely result in failure and recurrence of CSF leak.

PMID- 28452711
TI  - Office-based rhinologic surgery: A modern experience with operative techniques
      under local anesthetic.
AB  - BACKGROUND: Office-based rhinologic procedures have become popularized in recent
      years with the advent of several minimally invasive techniques. There is a
      paucity of literature, however, that supports more robust in-clinic procedures,
      e.g., true endoscopic sinus surgery (ESS). There is a high volume of this work
      being done at our center, and the objective of this article was to review the
      safety and tolerability of in-clinic surgeries. METHODS: A retrospective chart
      review was conducted. All the adult patients who underwent in-clinic sinonasal
      procedures and surgery with a minimum of 3 months of follow-up were included.
      Information regarding intra- and postoperative complications and revision
      procedures were recorded. For the ESS procedures, the indication, sinuses
      operated on, and type of revision were also collected. RESULTS: A total of 315
      patients met the inclusion criteria. There were 166 turbinoplasties, 118 ESS, 35
      septoplasties, 34 rhinoplasties, and 4 septorhinoplasties performed. For the ESS
      procedures, 74 (62.7%) were bilateral, and experience was had operating in all
      paranasal sinuses. All ESS work involved opening diseased ostia and was more than
      just polypectomies. The mean follow-up for the ESS cases was 13.4 months (range,
      12-65 months). Complication rates and tolerability measures were comparable with
      those of other reported in-office sinonasal procedures performed with the patient
      under local anesthetic. CONCLUSION: Office-based rhinologic surgery was safe and
      well tolerated by the patients. The need for revision ESS in our series was low
      when considering the extent of surgery that was performed. An in-clinic procedure
      may avoid a general anesthetic in the operating room for appropriately selected
      patients.

PMID- 28452712
TI  - Low 22-Item Sinonasal Outcome Test Scores in Chronic Rhinosinusitis: Why Do
      Patients Seek Treatment?

PMID- 28452713
TI  - Decreased uncinate fasciculus tract integrity in male and female patients with
      PTSD: a diffusion tensor imaging study.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a disabling psychiatric
      disorder that has been associated with lower white matter integrity of tracts
      connecting the prefrontal cortex with limbic regions. However, previous diffusion
      tensor imaging (DTI) findings have been inconsistent, showing high variability in
      the exact location and direction of effects. METHODS: We performed probabilistic
      tractography of the bilateral uncinate fasciculus, cingulum and superior
      longitudinal fasciculus (both temporal and parietal projections) in male and
      female police officers with and without PTSD. RESULTS: We included 38 (21 men)
      police officers with and 39 (20 men) without PTSD in our analyses. Compared with
      trauma-exposed controls, patients with PTSD showed significantly higher mean
      diffusivity of the right uncinate fasciculus, the major white matter tract
      connecting the amygdala to the prefrontal cortex (p = 0.012). No other
      significant between-group or group * sex differences were observed. Mean
      diffusivity of the right uncinate fasciculus was positively associated with
      anxiety symptoms (r = 0.410, p = 0.013) in patients with PTSD as well as with
      amygdala activity (r = 0.247, p = 0.038) and ventromedial prefrontal cortex
      (vmPFC) activity (r = 0.283, p = 0.016) in all participants in response to happy
      and neutral faces. LIMITATIONS: Our specific sample of trauma-exposed police
      officers limits the generalizability of our findings to other PTSD patient groups
      (e.g., civilian trauma). CONCLUSION: Patients with PTSD showed diminished
      structural connectivity between the amygdala and vmPFC, which was correlated with
      higher anxiety symptoms and increased functional activity of these brain regions.
      Our findings provide additional evidence for the prevailing neurocircuitry model
      of PTSD, postulating that ineffective communication between the amygdala and
      vmPFC underlies decreased top-down control over fear responses.

PMID- 28452715
TI  - Benefit of Using the Prosthesis with Sound Generators in Individuals with
      Tinnitus Associated With Mild to Moderately Severe Hearing Loss.
AB  - INTRODUCTION: One of the treatments currently available for the remission of
      tinnitus, when associated with hearing loss is the use of hearing aids with sound
      generator. Such treatment is based on the capability that the human brain has to
      get used to a new sound over another. OBJECTIVE: To describe the results found in
      a group of people who have undergone treatment with sound generators. Method:
      Audiologic follow-up protocols of 25 adult subjects with hearing loss and
      complaint of tinnitus were analyzed. It was applied: free field audiometry with
      hearing aids, Visual Analog Scale to determine the degree of annoyance of the
      tinnitus and Tinnitus Handicap Inventory to assess tinnitus impact on the quality
      of life before and after treatment. RESULTS: After the use of hearing aids there
      was significant improvement in hearing thresholds; there was a significant
      reduction in the degree of annoyance caused by tinnitus; there was a significant
      reduction of tinnitus and, consequently, on the quality of life of the
      respondents. CONCLUSION: This study allowed the verification that the use of
      hearing aids with sound generator is a good resource for the treatment of
      tinnitus associated with mild to moderately severe hearing loss.

PMID- 28452716
TI  - Can CK-MB be used as a marker in benign paroxysmal positional vertigo attack?
AB  - OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) is one of the main causes
      of vertigo. More than 90% of cases of positional vertigo and nystagmus can be
      associated with BPPV. There is no known specific laboratory test for BPPV.
      Because of the possible muscle activity in BPPV (especially result of nause,
      vomiting and increasing heart rate) we thought the CK-MB levels may change in
      this situation. The purpose of this study was to investigate the relation between
      serum CK-MB levels and BPPV and attacks. MATERIALS AND METHODS: The medical
      records of 35 patients with BPPV presenting to our clinic between November 2014
      and November 2015 were investigated retrospectively. Thirty-two control patients
      with no vertigo, muscular or cardiac disease and with measured CK-MB levels were
      randomized into a control group. Both groups' existing CK-MB levels were obtained
      from the patient records. CK-MB values measured before BPPV attack from 11
      patients in the patient group were also recorded. RESULTS: The patient and
      control groups were similar in terms of demographic parameters. CK-MB values at
      time of attack in the patient group ranged between 5.4 and 38.9 (mean: 19.67 +/-
      6.81), while control group values ranged between 12 and 27.9 (mean: 20.31 +/-
      4.54). CK-MB values in 11 patients in the patient group measured before attack
      ranged between 8.9 and 24 (mean: 17.02 +/- 4.97), and CK-MB values during attack
      ranged between 9 and 34 (mean: 19.74 +/- 7.64). CONCLUSION: Although CK-MB
      elevation at time of attack was determined in patients with BPPV, this was not
      statistically significant.

PMID- 28452714
TI  - The MBD7 complex promotes expression of methylated transgenes without
      significantly altering their methylation status.
AB  - DNA methylation is associated with gene silencing in eukaryotic organisms.
      Although pathways controlling the establishment, maintenance and removal of DNA
      methylation are known, relatively little is understood about how DNA methylation
      influences gene expression. Here we identified a METHYL-CpG-BINDING DOMAIN 7
      (MBD7) complex in Arabidopsis thaliana that suppresses the transcriptional
      silencing of two LUCIFERASE (LUC) reporters via a mechanism that is largely
      downstream of DNA methylation. Although mutations in components of the MBD7
      complex resulted in modest increases in DNA methylation concomitant with
      decreased LUC expression, we found that these hyper-methylation and gene
      expression phenotypes can be genetically uncoupled. This finding, along with
      genome-wide profiling experiments showing minimal changes in DNA methylation upon
      disruption of the MBD7 complex, places the MBD7 complex amongst a small number of
      factors acting downstream of DNA methylation. This complex, however, is unique as
      it functions to suppress, rather than enforce, DNA methylation-mediated gene
      silencing.

PMID- 28452717
TI  - Relationship between Subjective Tinnitus Perception and Psychiatric Discomfort.
AB  - INTRODUCTION: Tinnitus patients have higher risk of developing anxiety-depressive
      disorders and decreased quality of life. The reasons why selected patients are
      able to cope with chronic tinnitus, whereas it represents a disabling symptom for
      others remain under discussion. OBJECTIVES: the objective of the study was to
      determine the tinnitus-related degree of distress along with the prevalence of
      anxiety-depression disorders in a sample of eighty patients referring for chronic
      tinnitus at the Department of Otolaryngology of Catholic University of Rome from
      March to September 2015. MATERIALS AND METHODS: We administered to all patients
      the Italian versions of Tinnitus Handicap Inventory (THI) and Hospital Anxiety
      and Depression Scale (HADS). Furthermore we investigated the correlation among
      patient's discomfort, severity of hearing loss and age. RESULTS: Average THI
      score was 40.85, meaning moderate degree of discomfort; 57.5% of the patients
      showed HADS scores consistent with high risk of psychiatric comorbidities. A
      significant linear correlation between THI and HADS scores was demonstrated.
      CONCLUSION: We suggest that patients with severe tinnitus-related distress are
      routinely invited to accomplish psychometric questionnaires, to assess the
      possibility of a neuropsychiatric evaluation and/or specific pharmacological
      planning. At this purpose we recommend the administration of HADS, as a reliable
      and quick instrument.

PMID- 28452718
TI  - Tinnitus in Temporomandibular Joint Disorders: Is it a Specific Somatosensory
      Tinnitus Subtype?
AB  - ABSTRACT: The most significant otologic symptoms, consisting of ear pain,
      tinnitus, dizziness, hearing loss and auricolar "fullness", generally arise
      within the auditory system, often are associated with extra auricolar disorders,
      particularly disorder of the temporo-mandibular joint. In our study we examined a
      sample of 200 consecutive patients who had experienced severe disabling symptom.
      The patiens came to maxillofacial specialist assessment for temporomandibular
      disorder. Each patient was assessed by a detailed anamnestic and clinical
      temporomandibular joint examination and they are divided into five main groups
      according classification criteria established by Wilkes; tinnitus and subjective
      indicators of pain are evaluated. The results of this study provide a close
      correlation between the joint pathology and otologic symptoms, particularly
      regarding tinnitus and balance disorders, and that this relationship is greater
      the more advanced is the stage of joint pathology. Moreover, this study shows
      that TMD-related tinnitus principally affects a younger population (average fifth
      decade of life) and mainly women (more than 2/3 of the cases). Such evidence
      suggests the existence of a specific tinnitus subtype that may be defined as "TMD
      related somatosensory tinnitus".

PMID- 28452719
TI  - Anosmia treatment by platelet rich plasma injection.
AB  - INTRODUCTION: Platelets are known for their key role in hemostasis and
      controlling the bleeding after injury. The fact that platelets secrete growth
      factors and active metabolites means that their applied use can have a positive
      influence in clinical situations requiring rapid healing and tissue regeneration.
      OBJECTIVES: Platelet Rich Plasma has been described as a promising but unproven
      therapy. MATERIALS AND METHODS: Whole blood was undergoing one stage of
      centrifugation. The whole blood was then separated into three layers. One ml of
      the lowest layer of plasma was administered to the patient's nose. RESULTS: After
      the third and finally the fourth therapy, 4 of 5 patients said that "their smell
      came back", while the remaining one patient said that he could smell a lot but
      not everything. CONCLUSION: Based on our results, platelet rich plasma
      administration to the olfactory region could be a promising, last chance therapy
      for complete anosmia.

PMID- 28452720
TI  - CARCINOSARCOMA OF SKIN (SARCOMATOID CARCINOMA) - A RARE NON-MELANOMA SKIN CANCER
      (CASE REVIEW).
AB  - Non-melanoma skin cancer incidence is rising worldwide. The leading neoplasias
      are basal cell carcinoma and squamous cell carcinoma. We report on an 88-year-old
      female patient with a rapidly grown, symptomless, exophytic tumor of the
      supraclavicular area. Examination at the dermatology department has revealed a
      firm, exophytic, reddish tumor covered by crusts, about 4 cm in diameter and
      easily movable to the ground. The tumor was removed by delayed Mohs surgery (R0
      resection). The resulting defect was closed by tissue expansion. Nodal metastases
      were ruled out by ultrasound. Histologic investigation revealed a biphasical
      nodular tumor composed of partly fibrous spindle cellular elements, partly myxoid
      and chondroid mesenchymal components with cellular atypia, atypical mitoses and
      focal necrosis. Some multinucleated tumor cells were noted. Trabecular and island
      like solid epithelial tumor components demonstrated increased mitotic activity
      and cellular atypia. There was no vascular invasion. The diagnosis of a basaloid
      carcinosarcoma was confirmed. Basaloid carcinosarcoma is an extremely rare
      cutaneous neoplasia with less than 30 patients reported. Complete wide excision
      or Mohs surgery are the favored treatment options.

PMID- 28452721
TI  - ILVEN - COMPLETE REMISSION AFTER ADMINISTRATION OF TOPICAL CORTICOSTEROID (CASE
      REVIEW).
AB  - Inflammatory linear verrucous epidermal nevus (ILVEN) is a relatively rare
      disorder with an onset at early age, consisting of pruritic linear papules and/or
      plaques and histologic features resembling psoriasis or lichenoid dermatitis. The
      disease is a version of mosaicism caused by somatic mutations. ILVEN belongs to
      the heterogeneous group of congenital hamartomas of embryonal ectodermal origin,
      as a variant of verrucous epidermal nevus, representing approximately 5% of all
      epidermal nevi, with predominance in females and with general therapeutic
      resistance. We report on an 18-month-old female patient with ILVEN, who failed to
      respond to topical tacrolimus, but achieved complete resolution with topical
      application of momethasone furoate 0.1% under occlusion for 2 weeks, with no
      signs of recurrence to date. Consequent topical therapy can provide excellent
      results in young children.

PMID- 28452722
TI  - AN ERUPTION PATTERN OF DECIDUOUS TEETH IN CHILDREN BORN WITH FETAL MACROSOMIA
      DURING THE FIRST YEAR OF LIFE.
AB  - The paper aims at studying the effect of body overweight at birth on the dental
      health of 482 children in the Kharkiv City (Ukraine) during their first year of
      life over the 2001 and 2013 interval. The macrosomia set is comprised of the
      medical records of the children born with fetal macrosomia, and the normosimia
      set of the medical records of the children born with weight and height that
      correspond to the gestation age. The gestation age of all children is 37 to 42
      weeks'. To determine the average time of first tooth eruption and deciduous teeth
      growth rate for each of the sets under study, we have used the hypothesis about a
      linear dependence between the number of erupted teeth and the age of the child.
      Processing statistical data is performed applying the multiple linear regression
      analysis. The reasons for macrosomia in the children are examined. The number of
      pregnancies and deliveries influence the likelihood of having a child with fetal
      macrosomia. A greater likelihood of having a child with fetal macrosomia in the
      older parents is not found. The correlation between the states of a child at
      birth (macrosomia/normosimia) and terms of deciduous tooth eruption (the
      delayed/timely/early eruption) expressed in a number of teeth at the age of one
      year is determined. The difference in the teeth growth rate between the boys and
      girls within the both sets are insignificant. The children born with macrosomia
      have a lower rate (approximately 0.1 tooth per month) of teeth growth and a
      greater spread in the number of teeth that erupt by a certain age.

PMID- 28452723
TI  - [ULTRASOUND DIAGNOSIS OF FORMS IATROGENIC MAXILLARY SINUSITIS].
AB  - Purpose of the study was to evaluate the effectiveness of diagnosis of the mixed
      form of iatrogenic maxillary sinusitis. Was studied 21 (100%) patients with a
      fragment of a remote tooth in the sinus - 12 (57,1%), with a filling material - 9
      (42,9%) in the maxillary sinus with an ultrasound diagnostic device ACUSON X 500,
      ATSmod.539 (SIEMENS) in B-mode using a linear sensor with a working surface
      length of 37 mm, with a frequency mode of 7.5-10 MHz. The evaluation of
      pathological changes in the sinuses and their interpretation were carried out
      according to the criteria given in the literature. Analysis of the results of the
      study in the tables is presented in absolute values (abs.). In fractions
      expressed in percentages (P) and in share errors (S+/-P). Statistical analysis of
      the absolute values of the obtained results was carried out by the Student
      method, comparison of the shares by the chi2 method. Edema of the facial soft
      tissues was revealed in 28.1% of cases, the average soft tissue thickness from
      the projection of the anterior wall of the affected maxillary sinus was 13.0+/
      2.7 mm, the thickness of the mucosa covering the front wall was 10.1+/-1.7 mm.
      Healthy-isoechogenic sinus mucosa is noted in 8 (38%) cases. Echosignal weakening
      (hypoechoinality) due to the liquid component is in 5 (23,8%) sinuses (p>0.05).
      Hyperechoic contents were found in 7 (33.3%) sinuses, Anehogenous contents -
      cystically altered mucosa (14.3%) Differences between the incidence of sinuses
      with hyperechoic contents and unchanged sinuses with a mixed form of sinusitis
      were statistically significant (p<0.05). Thus, the criteria of a healthy sinus
      (in 38,0-47,6% of cases) and chronic inflammation (33,3-38,0%) were often met.
      The acute phase of the inflammatory process was noted in 23.8%. In the mixed form
      of iatrogenic maxillary sinusitis, both the acute phase of the disease and the
      exacerbation of chronic inflammation occur, which proceed according to the type
      of catarrhal sinusitis. At the same time, hyperechoinality of the mucosa is
      equally observed, indicating sclerotic changes - with exacerbation of chronic
      sinusitis, and acoustic shade - with primary sinusitis and absence of chronic
      inflammation in the sinus. In the absence of severe clinical symptoms of acute
      sinusitis, according to ultrasound, it is possible to clarify the presence or
      absence of fluid in the sinus. In the latter case, surgical treatment without
      preliminary antibacterial therapy is indicated (in our study - 76.2% for patients
      with a foreign body in the sinus).

PMID- 28452724
TI  - [ORTHOTOPIC URINE DERIVATION AFTER RADICAL CYSTECTOMY (REVIEW)].
AB  - In this article modern methods of choice in orthotopic urine derivation and
      reconstruction of urine reservoir from different parts of digestive trac are
      reviewd. Orthotopic replacement of urinary bladder is a standart after radical
      cystectomy, which provides recovery of urination, full social and psychological
      rehabilitation of patients. But radical cystectomy with orthotopic reservoir is
      the method of treatment which causes many complications in early and late
      postoperative periods. That requires multimodal approach to correction. Strongly
      recommended methods of urine derivation should be widely used in specialized
      surgical centers.

PMID- 28452725
TI  - [CLINICAL-HEMODYNAMIC PECULIARITIES OF THE COURSE OF HEMODYNAMIC ISCHEMIC STROKE
      IN ACUTE PERIOD].
AB  - : The aim of the research is to study the peculiarities of cardiac morphometric
      parameters, the parameters of central hemodynamics and their impact on the course
      of hemodynamic ischemic stroke in acute period. 116 patients were performed Echo
      Doppler-cardiography in acute period of hemodynamic ischemic stroke in order to
      evaluate cardiac morphometric parameters. These patients were also performed
      transcranial duplex scanning. The results established that among significant
      clinical factors that influence the course of the acute period of hemodynamic
      ischemic stroke the most important are: the size of the focus, the level of
      consciousness on the 1st day, primary systolic arterial pressure, age of the
      patient. Hemodynamic ischemic stroke occurs on the background of changes of
      cardiac morphometric parameters and the disorders of the central hemodynamics.
      There is a close connection between the severity of hemodynamic ischemic stroke
      on the 7th and 14th day with the ejection fraction, the size of left atrium, the
      thickness of posterior wall of left ventricle, final diastolic size of left
      ventricle. The interrelation between the parameters of cerebral hemodynamics and
      cardiac morphometric parameters was established. CONCLUSIONS: cardiac
      morphometric parameters and parameters of central hemodynamics can be predictors
      of the course of hemodynamic ischemic stroke in acute period.

PMID- 28452726
TI  - [NESFATIN-1 ACTIVITY IN PATIENTS WITH ESSENTIAL HYPERTENSION AND PREDIABETES,
      TYPE 2 DIABETES].
AB  - Essential hypertension (EH) is one of the important problems and comorbidity
      negatively affects the prognosis of the disease. Substantial thing is
      investigation of metabolic substances that influence the carbohydrate profile.
      Aim - investigation of the nesfatin-1 activity in patients with Essential
      hypertension and prediabetes/type2 diabetes. 83 patients with EH were examined
      and divided into groups according to dysglicemia and abdominal obesity.
      Significant increasing of nesfatin-1 in patients with EH 7,81+/-0,26 ng/ml was
      found comparing to controls 4,54+/-0,13 ng/ml, p<0,05. In patients with EH with
      obesity, without dysglicemia level of nesfatin-1 was higher than in obese ones
      (8,31+/-0,19 ng/ml, 7,44+/-0,13 ng/ml correspondebtly (p=0,003)). In patients
      with EH and dysglicemia the tendency to decreasing of nesfatin in case of
      accompanied obesity was found. Correlation of nesfatin-1 and systolic blood
      pressure (r=0,34, p<0,05) was revealed in patients with EH, abdominal obesity
      without dysglicemia. Increasing of nesfatin-1 in EH comparing to controls was
      found. Correlations of nesfatin-1 with carbohydrate profile components showed
      possible involvement of nesfatin-1 in carbohydrate disorders. Controversies of
      nesfatin-1 data in patients with EH, dysglicemia, obesity, possibly, connected
      with polymorbidity and needs further investigation.

PMID- 28452727
TI  - [THE INFLUENCE OF LIFESTYLE ON BIOMARKERS OF FIBROSIS IN PATIENTS WITH STABLE
      CORONARY HEART DISEASE ON THE BACKGROUND OF NON-ALCOHOLIC FATTY LIVER DISEASE].
AB  - Purpose - to assess the impact of lifestyle on non-alcoholic fatty liver disease
      (NAFLD) activity by influencing the fibrotic processes and hepatic steatosis in
      patients with stable coronary heart disease (CHD). 105 patients with stable CHD,
      combined with NAFLD were observed: Group I - control group; Group II - basic
      group. In each group, patients with non-alcoholic steatosis (subgroup A) and non
      alcoholic steatohepatitis (subgroup B) were isolated. General clinical
      examination, electrocardiography, coronary angiography, echocardiography, liver
      functional state, serum lipid profile, fasting glucose, markers of fibrosis were
      conducted to all patients. After treatment in patients of Group II positive
      changes in all parameters vs. basal levels and the control group were found:
      significantly decreased body mass index, alpha-2-macroglobulin and type IV
      collagen levels; increased apolipoprotein A1 and haptoglobulin levels; decreased
      severity of dyslipidemia; improved parameters of the liver functional state.
      Modification of lifestyle of patients with stable CHD influences positively on
      the NAFLD course, reducing disease activity by inhibiting fibrotic processes and
      hepatic steatosis that, in general, inhibits the progression of this comorbid
      disorder.

PMID- 28452728
TI  - CYTOKINE PRODUCTION PECULIARITIES IN DIFFERENT FORMS OF EPSTEIN-BARR VIRUS
      INFECTION.
AB  - In article presented results of the study of basic levels of regulatory cytokines
      in patients with various forms of Epstein-Barr virus (EBV) infection. Analysis of
      the dynamics of cytokine profile in patients with EBV infection revealed the
      opposite changes studied synthesis of proinflammatory and anti-inflammatory
      cytokines, which was the basis for the establishment of the four types of immune
      response. The findings confirm the existence of cytokine imbalance with EBV
      infection. The established types of immune responses indicate inadequate cell
      humoral reactivity in a long persistence of EBV, which manifests a tendency to
      suppression of cell-mediated and humoral immune response enhancement mechanisms
      and displayed in the clinical and biochemical manifestations of the disease, and
      also leads to prolonged undulating course.

PMID- 28452729
TI  - QUALITY OF LIFE OF CHILDREN WITH RICKETS IN YOUNG AGE IN ARMENIA.
AB  - Quality of Life (QL) currently is one of the most important criteria for
      evaluating a child's function. The main characteristics of QL in pediatrics are
      the psychological, physical and social functioning of the body. Integral
      characteristics of QOL based on the subjective perception of the components of
      the child and his parents. As a result of the official statistics and our
      research it turned out that children in this age-group more often suffer from
      intestinal infections, anemia, hypertrophy, rickets, skin and subcutaneous fiber
      disease, deficiencies occurring in prenatal period. The aim of the research is to
      evaluate the peculiarities of QL criteria change in case of rickets. So far in
      Armenia there were no tools of QL assessment of children of an early age, thereby
      the most acceptable questionnaire of QUALIN was used to create Armenian version
      on its basis. We cooperated with MAPI institute and the authors of QUALIN(Qualite
      de vie du Nourisson) questionnaire (Manificat S., Dazord A,) and got MAPI's
      permission to apply the questionnaire in the Republic of Armenia. The
      questionnaire QUALIN was selected for studying children's QL. The results show
      that the QL of children with rickets is lower than the QL of the ones who are
      healthy. The difference is more vividly expressed in the following parameters of
      QL: neuropsychological development and physical health, the ability to stay
      alone. In this case the pediatricians have given lower mark of QL than parents.
      We think that one of the possible motives of such diversity is the professional
      approach of doctors who estimated the QL more strictly than parents did. So
      QUALIN international questionnaire can be applied to estimate the peculiarities
      of QL criteria change of children with rickets at an early age.

PMID- 28452730
TI  - [MICROELEMENT STATUS IN CHILDREN WITH ENLARGED THYROID GLAND IN WEST KAZAKHSTAN
      REGION].
AB  - Aim of research - analysis of content of microelements in hair of children with
      thyromegaly living in the West Kazakhstan region. 159 school children of 6-12
      years constantly living in this region were studied. Thyroid volume was measured
      by ultrasonography using an ultrasound scanner and evaluated according to body
      surface area and the gender in accordance with the WHO recommendations (2007).
      Microelements were measured by inductively coupled plasma mass spectrometry on
      NexION 300D (PerkinElmer Inc., USA). Excess value of the content of boron at
      32.29% and silicon at 21.44% was found in children with goiter compared with
      those from control group. There was a reduction of cadmium at 37.38%, manganese -
      26.48%, lead - 47%, vanadium - 15.5% compared with children with the normal
      volume of the thyroid gland. Correlation analysis showed a positive association
      of thyroid volume and hair trace elements Cu (r=0.423; p=0.001) and Si (r=0.202;
      p=0.01) and between I in hair and Hg (r=0.2978; p=0.001). The results of the
      multiple regression analysis revealed that the amount of thyroid is positively
      related to the concentration of copper and silicon in hair, and in less degree
      negatively with vanadium. The effect of these elements is 23%. Also found a
      positive dependence of iodine in the hair from indicators of mercury and negative
      from beryllium. Children with goiter show increased content of boron and silicon
      in hair and the decreased level of cadmium, manganese, lead, vanadium. The
      content of iodine in hair of children depends on the indicators of mercury and
      beryllium.

PMID- 28452731
TI  - QUALITY OF LIFE OF PEOPLE LIVING WITH HIV: IDENTIFICATION OF THE DETERMINANTS.
AB  - The high prevalence rate of HIV worldwide, including the Republic of Kazakhstan
      (the RK), in large cities in particular, underlies the tremendous significance of
      this medical condition for society, economy, demography and healthcare. The
      objective of this study was to identify the most important determinants of
      quality of life (QL) of people living with HIV in a large city. The study was
      carried out in 3 stages. At the first stage, the HIV morbidity and PLH mortality
      figures over the period of 10 years (2005-2014) in a metropolis (the city of
      Astana) were analyzed in comparison to the general ones for the Republic. At the
      second stage, social and demographic charecteristics of the respondents, as well
      as characretistics of their HIV status and medical activity were received with
      the use of a 49 question enquiry that we developed. At the third stage, the QL of
      persons infected with HIV was studied. The general SF-36 questionnaire was the
      main tool of tracking the QL changes. The sample consisted of 170 respondents
      selected based random quota sampling. Comparison of the QL levels by gender
      showed that across the majority of scales of the physical health componentand in
      general across the physical health component, the QL levels for males were higher
      than for females. At the same time as for the psychological health component
      figures, general psychological health component and the majority of scales were
      higher for females, however, the differences across all the scales were
      statistically non-significant (r>0.05). The QL figures were higher for
      individuals with secondary vocational and higher education, as well as for
      married ones. Comparison of the QL figures showed no interdependence between them
      and the period of time after HIV status was determined. Addictive substance
      consumption was identified to decrease the QL of people living with HIV. The
      study allowed us to identify the role of independent variables influencing the
      quality of life of people living with HIV in a large city.

PMID- 28452732
TI  - [EPIZOOTOLOGICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF TULAREMIA IN GEORGIA].
AB  - The appropriate data as well as archival materials about the spread of Tularemia
      disease have been studied over of period from 1991-2014 in Georgia in order to
      evaluate the current situation in Kartli lowland foci as well as the main reasons
      of disease agent circulation and maintenance in the study area. 54 (24.6%) out of
      220 suspicious cases were laboratory confirmed during the study period. Most of
      confirmed cases - 32 (59.26%) have been detected in Shida Kartli focus among the
      old population during the outbreaks in the winter period. Tularemia causative
      agent has been isolated from the environmental object on 87 occasions, 50 (57.5%)
      of them have been found in Shida Kartli and 8 (9.2%) - in Kvemo Kartli lowland.
      Existence of rodents and ixodes ticks in Kartli lowland greatly supports keeping
      up Tularemia foci in this area. The common vectors and kind of storage of disease
      are considered to be different species of ixodes ticks especially D. marginatus,
      Haem. Punctata, Haem. Sulcata. It should be noted that reduction of intensity of
      Tularemia agent partially should be linked to the reduction frequency of planned
      and intentional researches during the last period of time.

PMID- 28452733
TI  - BIOLOGICAL ACTIVITY OF GREEN TEA EXTRACTS.
AB  - The purpose of our study was to determine effects of green tea extracts on the
      Jurkat cells incubated under oxidative stress conditions. The research was
      conducted on leukemic human mature T cells (Jurkat cells). For the modelling of
      oxidative stress 30% hydrogen peroxide (H2O2) (Sigma) (10 MUl, 25 MUl 50 MUl and
      100 MUl) was added to Jurkat cell suspension with subsequent incubation for 4, 6,
      8 and 24 h. Control group was represented by intact Jurkat cells. The assessment
      of cells proliferation activity (viability) was performed by MTT test. The
      viability of Jurkat cells incubated for 24 hours under acquit oxidative stress
      conditions dose-depenently, monotonically decreased (irreversibly at 100 MUM of
      H2O2 and reaches the 30% of intact Jurkat cells viability level at 50 MUM of
      H2O2). Low doses of H2O2 (10 MUl, 25 MUl H2O2) revealed cytotoxicity only within
      short term (8 hours) of the incubation, afterward the viability of Jurkat cells
      monotonically increased and after 24 hours it reached 43% and 56% of control
      level, respectively. Vitamins C and E revealed cytotoxic effect on intact Jurkat
      cells, while the C+V vitamins complex induced 2-fold stimulation of Jurkat cells
      viability. Under a moderate oxidative stress condition (25 MUl of H2O2) the
      complex of C + E vitamins revealed cytoprotective effect on Jurkat cells which
      may be related to ability of vitamin C to induce regeneration and to transform E
      vitamin tocopheroxyl free radicals into tocopherol. Green tea had no effect,
      green tea catechins revealed stimulatory effect, while green tea pectin - weak
      cytotoxic effect on intact Jurkat cells. Green tea and especially extracted
      catechins (but not pectin) revealed stimulatory effect on the viability of the
      Jurkat cells incubated under an oxidative stress condition. Our study results
      confirm the opinion that the natural compounds (green tea extracts) are harmless
      for normal cellular metabolism. Their differential effects on the "diseased",
      incubated under an oxidative stress cells are mediated via impact on signaling
      regulatory systems. On the basis of screening of green tea extracts it will be
      possible to select new high effective cytotoxic and cytoprotective compounds.

PMID- 28452734
TI  - [INFLUENCE OF IONIZING RADIATION ON THE LOCOMOTOR ACTIVITY AND BODY WEIGHT OF
      RATS].
AB  - The aim of our study was to study influence of ionizing radiation on the
      locomotor activity and body weight of rats, for this animals was irradiated by
      via inhalation. Beta- emitter 56Mn was obtained by neutron activation of powdered
      MnO2 by using nuclear reactor IVG.1M (experimental facility "Baikal-1",
      Kurchatov, Kazakhstan). Exposure of rats to radioactive powder had two way, the
      first experiment was contained only air filter for animal's breathing and the
      second with the system of forced ventilation. Also we developed the method for
      observation of the locomotor activity of rats, based on quantitative data. The
      experiment was conducted on 8 "Wistar" breed white laboratory rats. Statistical
      analysis was performed using descriptive statistics and non-parametric test.
      Based on our data, we can say that our method has the advantage over the others
      is that there is no need to move about the animal out of the box in the test
      field. So we reduce animal stress factor, as the transfer of an animal from one
      to second place creates additional stress for him. The initial activity of the
      pulverized powder in both experiments were 2,74x108Bq, but in the second
      experiment when we used the system of forced ventilation, internal radiation
      doses were 0.041+/-0.0075 Gy, this didn't have effect on locomotor activity of
      rats (Z= -0,841, r=0,4). In the first experiment where we used only air filter
      for animal's breathing internal radiation doses were 0.15+/-0.025 Gr, that showed
      a decrease in locomotor activity in rats (Z=-6,653, r=0,001). After exposure to
      ionizing radiation changes in the mammals' weight were not found. Thus, based on
      our data we have made conclusion, that even after a single irradiation at low
      dose 0.15+/-0.025 Gr changes occur in the nervous system.

PMID- 28452735
TI  - [EFFECT OF ACETYLCYSTEINE, CORVITIN AND THEIR COMBINATION ON THE FUNCTIONAL STATE
      OF LIVER IN RATS WITH PARACETAMOL INDUCED TOXIC HEPATITIS].
AB  - Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more
      than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant
      hepatitis and hepatocellular failure, the states requiring liver transplantation.
      The paracetamol induced liver toxicity is related with accumulation of its toxic
      metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and
      enhances peroxidation of lipids, disturbs the energy status and causes death of
      hepatocytes. During our research we investigated and assessed the efficacy of
      acetylcysteine, corvitin and their combination in rat model of paracetamol
      induced acute toxic hepatitis. The study was performed on mature white male
      Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5
      groups (10 rats in each group). To get the model of acute toxic hepatitis single
      intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic
      hepatitis was treated with intrapertoneal administration of 40mg/kg
      acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs.
      Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic
      hepatitis improved the liver function, decreased relative mass of the liver and
      animal mortality. The treatment of toxic hepatitis was most effective in the case
      of simultaneous administration of acetylcysteine and corvitin. The normal value
      of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated
      bilirubin) was reached and mortality was not more observed. On the bases of
      obtained data was concluded that acetylcysteine and corvitin have almost equal
      hepatoprotective activity. The combination of two drugs actually improves the
      liver function. The most pronounced hepatoprotective effect may be due to
      synergic action of acetylcysteine and corvitin and such regime can be recommended
      for correction of liver function.

PMID- 28452736
TI  - [ACTION OF L-CARNITINE, CORVITIN AND THEIR COMBINATION ON FUNCTIONAL STATE OF
      LIVER IN EXPERIMENTAL MODEL OF REYE SYNDROME IN RATS].
AB  - Administration of Aacetylsalicylic acid in children with viral infections
      (influence B, chickenpox) can be related with development of Reye syndrome -
      severe encephalopathy and liver insufficiency with mortality in 50% of cases.
      During Reye syndrome most important is deficiency of carnitine and hepatocyte
      damage. Decreased amount of carnitine impairs the energy function of mitochondria
      and gluconeogenesis as well as production of urea. As a result develops toxic
      encephalopathy and liver insufficiency. The goal of the research was assessment
      of efficacy of L-Carnitine, Corvitin and their combination on functional state of
      liver in experimental model of Reye Syndrome in rats. The study was performed on
      mature white male Wistar rates with body mass 150-180g. 50 rats were randomly
      divided into 5 groups (10 rats in each group). The model of Reye syndrome was
      induced in accordance with A.Vengersky's method. Intraperitoneal administration
      of 4-pentenoic acid was performed once daily during seven days, the used dosage
      was 20mg/kg. The treatment of toxic hepatitis was carried with intraperitoneal
      administration of L-Carnitine 300mg/kg, Corvitine 100mg/kg and concurrent
      administration of these drugs. Monotherapy with Corvitin and L-Carnitin
      successfully improved liver function and equally decreased indicators of
      hepatocyte's cytolyses and increased levels of glucose and urea. The markers of
      cholestasis was slightly more improved during use of L-Carnitine. Simultaneous
      use of both drugs was effective in rats with Reye syndrome, indicators of liver
      damage normalized and herewith, no mortality outcome was observed. The most
      pronounced hepatoprotective effect of concurrent administration of L-Carnitine
      and Corvitin may be due to synergic action of these drugs and such regime can be
      recommended for correction of liver function during Reye syndrome.

PMID- 28452737
TI  - IMMUNOLOGICAL DISTRESS IN EXPERIMENTAL CRANIAL TRAUMA COMBINED WITH INSULIN
      DEPENDENT DIABETES (EXPERIMENTAL STUDY).
AB  - This article describes the immunological events and investigates important
      mediators of the inflammatory immune response after experimental cranial trauma
      combined with type I diabetes. It was shown that the rats with induced diabetes
      and traumatic brain injury suffered more profound damage to the immune system
      that was not restored back to the basal level within 14 days. Proinflammatory
      cytokine concentrations increased, while anti-inflammatory cytokine
      concentrations decreased by day 14, increasing risk for systemic inflammatory
      response syndrome and multi-organ failure. Factors responsible for humoral
      immunity and cell-mediated immunity were consistently lower by day 14, which
      might make diabetic rats more susceptible to infections compared to rats with
      brain injury alone.

PMID- 28452738
TI  - DEVELOPMENT OF LC-MS/MS METHOD FOR DETERMINATION OF THE OLANZAPINE IN HUMAN
      PLASMA.
AB  - The study aim was to develop a validated selective, reproducible and sensitive
      Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS) method for
      qualitative and quantitative determination of olanzapin (OLZ ) in human plasma.
      For isolation was used solid phase extraction with the Gilson GX-271 ASPEC Solid
      phase extraction system, cartridge Supelclean LC-18 SPE 500mg. Elution solvent
      contained 40mL of isopropanol, 4mL of concentrated ammonium hydroxide and 156mL
      of freshly prepared methylene chloride. Samples containing OLZ and IS were
      chromatographed on AGILENT TECHNOLOGIES 1290 Infinity AGILENT TECHNOLOGIES 6460
      Triple quad LC-MS/MS system. Separation was performed by isocratic elution on
      Zorbax Eclipse plus C18 (100'4.5 mm, 3.8 um) column, equipped with pre-column:
      UHPLC GUARD Zorbax Eclipse plus C18 (5*2.1 mm, 3.8 um); column temperature was 35
      degrees C. The mobile phases consisted of 0.1 % water solution of formic acid
      HCOOH (H2O):0.1 % acetonitrile solution of formic acid HCOOH (CH3CN) in 70 :30
      (v/v) proportion. The flow rate was 0.4 mL/min. Determination was performed on a
      triple-quadrupole mass spectrometer employing electrospray ionization technique
      (ESI+), operating in multiple reaction monitoring (MRM) and positive ion mode.
      Total chromatographic run time was 5 min. The optimized MRM transitions for OLZ
      were m/z 313 (r) 256, m/z 313 ->213 and m/z 313->198 as the quantitative and
      confirmative traces, respectively. Method was validated on following parameters:
      specificity, linearity, LLOQ, accuracy and precision, recovery, matrix effect and
      stability. The method was subsequently applied to in vitro plasma samples for
      determination of OLZ. The obtained data allows the opportunity for forensic
      investigation of the intoxication in postmortem cases.

PMID- 28452739
TI  - [EXPERIMENTAL MODEL AND CURRENCY OF EXPERIMENT OF DISTANT RESULTS OF LEAD
      EXPOSITION].
AB  - In order to explore the distant results of exposition of little doses of lead,
      for the objective of the experiment model we have selected 32 mongral rats, of
      different age, but aged of both sex. Experimental animals were divided in two
      groups. During first two month from the beginning of the experiment, together
      with permissible food, animals were given the water, in which was open Pb(NO3)2 -
      to first group 1.5 mg on kg/weight and to II group 15 mg on kg/weight during the
      day and night. Before the beginning of the experiment, in the time of process and
      after it, observation was conducted, description and collection of photo-video
      materials about the behavior of animals, physiological parameters, possible
      change of weight, clear-sighted changes in appearance. During the autopsy of the
      animal, died during the experiment, it turned out that the reason of the death
      was acute heart failure caused by septicopyemia, the bilateral abscess pneumonia
      and right sided purulent pleurisy. The reason of the death of second animal was
      DIC (disseminated intravascular coagulation) Syndrome and the polyorganic
      pathology caused by it. We made the Nembutal injection to third animal because
      there was detected the 50*40*20 sized subcutaneous formation on the right surface
      of the chest, that turned out to be the breast adenoma with cystic fibrosis.
      After the completion of the experiment of distant results of lead exposition,
      surviving rats before autopsy will be dropped to sleep with high dose of drugs in
      compliance with the "Guidelines of animal care and ethical behavior", taken
      material will be processed for histopathological (in case of necessity
      histochemical and imunomorphological) and electronic microscopic researches.

PMID- 28452740
TI  - Tunable electronic properties of monolayer silicane via fluorine doping: a first
      principles study.
AB  - The electronic structures of fluorine-doped monolayer silicane (F-silicane) are
      investigated using the density functional theory. We find that the concentration
      of fluorine has an effect on the electronic properties such as surface work
      function and energy band structure. The band gap of F-silicane decreases
      monotonously as the covering percentage of F increases. With favorable formation
      energy, moderate band gap and appropriate work function, 50% F doped silicane is
      expected to be a potential candidate for water splitting reaction.

PMID- 28452741
TI  - Pressure dependence of transverse acoustic phonon energy in ferropericlase across
      the spin transition.
AB  - We investigated transverse acoustic (TA) phonons in iron-bearing magnesium oxide
      (ferropericlase) up to 56 GPa using inelastic x-ray scattering (IXS). The results
      show that the energy of the TA phonon far from the Brillouin zone center suddenly
      increases with increasing pressure above the spin transition pressure of
      ferropericlase. Ab initio calculations revealed that the TA phonon energy far
      from the Brillouin zone center is higher in the low-spin state than in the high
      spin state; that the TA phonon energy depend weakly on pressure; and that the
      energy gap between the TA and the lowest-energy-optic phonons is much narrower in
      the low-spin state than in the high-spin state. This allows us to conclude that
      the anomalous behavior of the TA mode in the present experiments is the result of
      gap narrowing due to the spin transition and explains contradictory results in
      previous experimental studies.

PMID- 28452742
TI  - Size reduction-induced chain breaking in Haldane-chain compounds SrNi2-x Mg x
      V2O8 (x  =  0 and 0.1).
AB  - We report size reduction-induced chain breaking in the spin-1 Haldane-chain SrNi2
      x Mg x V2O8 (x  =  0 and 0.1) by magnetization and electron spin resonance
      measurements. For x  =  0.0, the magnetic susceptibility of all samples can be
      well described by a temperature-independent term, a Curie-Weiss term and a
      Haldane-gap term. This implies that a reduced sample grain size breaks the long
      chain and creates a considerable number of S  =  1/2 edge spins, resulting in the
      enhancement of magnetization and the decrease of Haldane gap in the samples.
      These edge spins as well as the other paramagnetic ions at grain boundary and
      surface might be weakly coupled with each other. For the Mg-doped sample with x 
      =  0.1, there are more S  =  1/2 spins creased in relative to x  =  0.0 because
      of a combined effect of lattice defects, Mg-doping and reduced size. In addition,
      the antiferromagnetic resonance of x  =  0.1 is also presented.

PMID- 28452743
TI  - Electronic structure and magneto-optical Kerr spectra of an epitaxial
      Ni54.3Mn31.9Sn13.8 Heusler alloy film.
AB  - In this joint experimental and ab initio study, we investigated the influence of
      chemical composition and martensitic phase transition on the electronic,
      magnetic, optical and magneto-optical properties of ferromagnetic shape-memory Ni
      Mn-Sn alloys. Optical properties and polar magneto-optical Kerr effect (MOKE)
      spectra for Ni-Mn-Sn alloy film of composition Ni54.3Mn31.9Sn13.8 deposited
      epitaxially on MgO(0 0 1) substrate were measured over the photon energy range
      [Formula: see text] eV, and the complete set of optical conductivity tensor
      elements were determined. To explain the microscopic origin of the optical and
      magneto-optical spectra, extensive first-principles calculations were made, using
      the spin-polarized fully relativistic linear-muffin-tin-orbital method. The
      electronic, magnetic and magneto-optical properties of Ni-Mn-Sn Heusler alloys
      were investigated for the cubic austenitic and 4O orthorhombic martensitic
      phases, in stoichiometric and off-stoichiometric compositions. The MOKE
      properties of Ni-Mn-Sn systems are very sensitive to deviation from
      stoichiometry. It was shown that the ab initio calculations reproduce
      experimental spectra well, and help to explain the microscopic origin of Ni-Mn-Sn
      optical and magneto-optical responses. The interband transitions responsible for
      the prominent structures in the Ni-Mn-Sn MOKE spectra have been identified-they
      come from relatively narrow energy intervals at several well-defined vicinities
      of high-symmetry directions of the Brillouin zone. Significant modification of
      the MOKE spectra can be considered as a fingerprint of martensitic phase
      transition in Ni-Mn-Sn alloys.

PMID- 28452744
TI  - Magnetic structure of Cu2MnBO5 ludwigite: thermodynamic, magnetic properties and
      neutron diffraction study.
AB  - We report on the thermodynamic, magnetic properties and the magnetic structure of
      ludwigite-type Cu2MnBO5. The specific heat, low-field magnetization and
      paramagnetic susceptibility were studied on a single crystal and combined with
      powder neutron diffraction data. The temperature dependence of the specific heat
      and the neutron diffraction pattern reveal a single magnetic phase transition at
      T  =  92 K, which corresponds to the magnetic ordering into a ferrimagnetic
      phase. The cation distribution and the values and directions of magnetic moments
      of ions in different crystallographic sites are established. The magnetic moments
      of Cu2+ and Mn3+ ions occupying different magnetic sites in the ferrimagnetic
      phase are pairwise antiparallel and their directions do not coincide with the
      directions of the principal crystallographic axes. The small value of the
      magnetic moment of copper ions occupying site 2a is indicative of partial
      disordering of the magnetic moments on this site. The magnetization measurements
      show a strong temperature hysteresis of magnetization, which evidences for field
      dependent transitions below the phase transition temperature.

PMID- 28452745
TI  - Fluid dynamics analysis of a gas attenuator for X-ray FELs under high-repetition
      rate operation.
AB  - Newtonian fluid dynamics simulations were performed using the Navier-Stokes
      Fourier formulations to elucidate the short time-scale (us and longer) evolution
      of the density and temperature distributions in an argon-gas-filled attenuator
      for an X-ray free-electron laser under high-repetition-rate operation. Both
      hydrodynamic motions of the gas molecules and thermal conductions were included
      in a finite-volume calculation. It was found that the hydrodynamic wave motions
      play the primary role in creating a density depression (also known as a filament)
      by advectively transporting gas particles away from the X-ray laser-gas
      interaction region, where large pressure and temperature gradients have been
      built upon the initial energy deposition via X-ray photoelectric absorption and
      subsequent thermalization. Concurrent outward heat conduction tends to reduce the
      pressure in the filament core region, generating a counter gas flow to backfill
      the filament, but on an initially slower time scale. If the inter-pulse
      separation is sufficiently short so the filament cannot recover, the depth of the
      filament progressively increases as the trailing pulses remove additional gas
      particles. Since the rate of hydrodynamic removal decreases while the rate of
      heat conduction back flow increases as time elapses, the two competing mechanisms
      ultimately reach a dynamic balance, establishing a repeating pattern for each
      pulse cycle. By performing simulations at higher repetition rates but lower per
      pulse energies while maintaining a constant time-averaged power, the amplitude of
      the hydrodynamic motion per pulse becomes smaller, and the evolution of the
      temperature and density distributions approach asymptotically towards, as
      expected, those calculated for a continuous-wave input of the equivalent power.

PMID- 28452746
TI  - Development of optical choppers for time-resolved measurements at soft X-ray
      synchrotron radiation beamlines.
AB  - Two types of optical choppers for time-resolved measurements at synchrotron
      radiation soft X-ray beamlines have been developed. One type uses an air-spindle
      type rotation mechanism with a two-stage differential pumping system to maintain
      the ultra-high vacuum of the X-ray beamline, and the other uses a magnetic
      bearing. Both can be installed at the soft X-ray beamlines at SPring-8, greatly
      improving the accessibility of pump-and-probe spectroscopy. The combination of X
      ray chopper and pump-and-probe photoemission electron microscope at SPring-8
      provides drastic improvements in signal-to-noise ratio and resolution compared
      with techniques using high-voltage gating of channel plate detectors. The
      choppers have the capability to be used not only at synchrotron radiation
      facilities but also at other types of soft X-ray and VUV beamlines.

PMID- 28452747
TI  - The coherent radiation fraction of low-emittance synchrotrons.
AB  - In this work the coherence properties of the synchrotron radiation beam from an X
      ray undulator in a fourth-generation storage ring are analyzed. A slightly
      focused X-ray beam is simulated using a wavefront propagation through a non
      redundant array of slits and the mutual coherence function is directly obtained
      and compared with the Gaussian-Schell approximation. The numerical wave
      propagation and the approximate analytical approaches are shown to agree
      qualitatively, and it is also shown that, when the coherent fraction is selected
      by a finite aperture before the focusing element, even achromatic focusing
      systems like total reflection mirrors become slightly chromatic. This effect is
      also well accounted for in the Gaussian-Schell model. The wavefront propagation
      simulation through the non-redundant array was repeated with an imperfect mirror
      demonstrating that, although the wavefront is distorted, its coherent length is
      practically unchanged.

PMID- 28452749
TI  - Fresnel zone plate with apodized aperture for hard X-ray Gaussian beam optics.
AB  - Fresnel zone plates with apodized apertures [apodization FZPs (A-FZPs)] have been
      developed to realise Gaussian beam optics in the hard X-ray region. The designed
      zone depth of A-FZPs gradually decreases from the center to peripheral regions.
      Such a zone structure forms a Gaussian-like smooth-shouldered aperture function
      which optically behaves as an apodization filter and produces a Gaussian-like
      focusing spot profile. Optical properties of two types of A-FZP, i.e. a circular
      type and a one-dimensional type, have been evaluated by using a microbeam knife
      edge scan test, and have been carefully compared with those of normal FZP optics.
      Advantages of using A-FZPs are introduced.

PMID- 28452748
TI  - SOLEIL shining on the solution-state structure of biomacromolecules by
      synchrotron X-ray footprinting at the Metrology beamline.
AB  - Synchrotron X-ray footprinting complements the techniques commonly used to define
      the structure of molecules such as crystallography, small-angle X-ray scattering
      and nuclear magnetic resonance. It is remarkably useful in probing the structure
      and interactions of proteins with lipids, nucleic acids or with other proteins in
      solution, often better reflecting the in vivo state dynamics. To date, most X-ray
      footprinting studies have been carried out at the National Synchrotron Light
      Source, USA, and at the European Synchrotron Radiation Facility in Grenoble,
      France. This work presents X-ray footprinting of biomolecules performed for the
      first time at the X-ray Metrology beamline at the SOLEIL synchrotron radiation
      source. The installation at this beamline of a stopped-flow apparatus for sample
      delivery, an irradiation capillary and an automatic sample collector enabled the
      X-ray footprinting study of the structure of the soluble protein factor H (FH)
      from the human complement system as well as of the lipid-associated hydrophobic
      protein S3 oleosin from plant seed. Mass spectrometry analysis showed that the
      structural integrity of both proteins was not affected by the short exposition to
      the oxygen radicals produced during the irradiation. Irradiated molecules were
      subsequently analysed using high-resolution mass spectrometry to identify and
      locate oxidized amino acids. Moreover, the analyses of FH in its free state and
      in complex with complement C3b protein have allowed us to create a map of
      reactive solvent-exposed residues on the surface of FH and to observe the changes
      in oxidation of FH residues upon C3b binding. Studies of the solvent
      accessibility of the S3 oleosin show that X-ray footprinting offers also a unique
      approach to studying the structure of proteins embedded within membranes or lipid
      bodies. All the biomolecular applications reported herein demonstrate that the
      Metrology beamline at SOLEIL can be successfully used for synchrotron X-ray
      footprinting of biomolecules.

PMID- 28452751
TI  - Transverse gradient in Apple-type undulators.
AB  - Apple-type undulators are globally recognized as the most flexible devices for
      the production of variable polarized light in the soft X-ray regime, both at
      synchrotron and free-electron laser facilities. Recently, the implementation of
      transverse gradient undulators has been proposed to enhance the performance of
      new generation light sources. In this paper it is demonstrated that Apple
      undulators do not only generate linear and elliptical polarized light but also
      variable transverse gradient under certain conditions. A general theoretical
      framework is introduced to evaluate the K-value and its transverse gradient for
      an Apple undulator, and formulas for all regular operational modes and different
      Apple types (including the most recent Delta type and Apple X) are calculated and
      critically discussed.

PMID- 28452750
TI  - Nanofabrication and characterization of a grating-based condenser for uniform
      illumination with hard X-rays.
AB  - In the development of full-field transmission X-ray microscopy for basic study in
      science and technology, a condenser capable of providing intense illumination
      with high uniformity and stability on tested specimens in order to achieve high
      quality images is essential. The latest design of a square-shaped condenser based
      on diffractive gratings has demonstrated promising uniformity in illumination.
      This paper describes in more detail the development of such a beam shaper for
      hard X-rays at 10 keV with regard to its design, manufacture and optical
      characterization. The effect of the grating profile on the diffracted intensity
      has been theoretically predicted by numerical simulation using the finite
      difference time-domain method. Based on this, the limitations of the grating
      based condenser are discussed.

PMID- 28452752
TI  - Effective aperture of X-ray compound refractive lenses.
AB  - A new definition of the effective aperture of the X-ray compound refractive lens
      (CRL) is proposed. Both linear (one-dimensional) and circular (two-dimensional)
      CRLs are considered. It is shown that for a strongly absorbing CRL the real
      aperture does not influence the focusing properties and the effective aperture is
      determined by absorption. However, there are three ways to determine the
      effective aperture in terms of transparent CRLs. In the papers by Kohn [(2002).
      JETP Lett. 76, 600-603; (2003). J. Exp. Theor. Phys. 97, 204-215; (2009). J.
      Surface Investig. 3, 358-364; (2012). J. Synchrotron Rad. 19, 84-92; Kohn et al.
      (2003). Opt. Commun. 216, 247-260; (2003). J. Phys. IV Fr, 104, 217-220], the
      FWHM of the X-ray beam intensity just behind the CRL was used. In the papers by
      Lengeler et al. [(1999). J. Synchrotron Rad. 6, 1153-1167; (1998). J. Appl. Phys.
      84, 5855-5861], the maximum intensity value at the focus was used. Numerically,
      these two definitions differ by 50%. The new definition is based on the integral
      intensity of the beam behind the CRL over the real aperture. The integral
      intensity is the most physical value and is independent of distance. The new
      definition gives a value that is greater than that of the Kohn definition by 6%
      and less than that of the Lengeler definition by 41%. A new approximation for the
      aperture function of a two-dimensional CRL is proposed which allows one to
      calculate the two-dimensional CRL through the one-dimensional CRL and to obtain
      an analytical solution for a complex system of many CRLs.

PMID- 28452753
TI  - Long, elliptically bent, active X-ray mirrors with slope errors <200 nrad.
AB  - Actively bent X-ray mirrors are important components of many synchrotron and X
      ray free-electron laser beamlines. A high-quality optical surface and good
      bending performance are essential to ensure that the X-ray beam is accurately
      focused. Two elliptically bent X-ray mirror systems from FMB Oxford were
      characterized in the optical metrology laboratory at Diamond Light Source. A
      comparison of Diamond-NOM slope profilometry and finite-element analysis is
      presented to investigate how the 900 mm-long mirrors sag under gravity, and how
      this deformation can be adequately compensated using a single, spring-loaded
      compensator. It is shown that two independent mechanical actuators can accurately
      bend the trapezoidal substrates to a range of elliptical profiles. State-of-the
      art residual slope errors of <200 nrad r.m.s. are achieved over the entire
      elliptical bending range. High levels of bending repeatability (DeltaR/R = 0.085%
      and 0.156% r.m.s. for the two bending directions) and stability over 24 h
      (DeltaR/R = 0.07% r.m.s.) provide reliable beamline performance.

PMID- 28452754
TI  - Understanding the instrumental profile of synchrotron radiation X-ray powder
      diffraction beamlines.
AB  - A Monte Carlo algorithm has been developed to calculate the instrumental profile
      function of a powder diffraction synchrotron beamline. Realistic models of all
      optical elements are implemented in a ray-tracing software. The proposed approach
      and the emerging paradigm have been investigated and verified for several
      existing X-ray powder diffraction beamlines. The results, which can be extended
      to further facilities, show a new and general way of assessing the contribution
      of instrumental broadening to synchrotron radiation data, based on ab initio
      simulations.

PMID- 28452755
TI  - Non-contact luminescence lifetime cryothermometry for macromolecular
      crystallography.
AB  - Temperature is a very important parameter when aiming to minimize radiation
      damage to biological samples during experiments that utilize intense ionizing
      radiation. A novel technique for remote, non-contact, in situ monitoring of the
      protein crystal temperature has been developed for the new I23 beamline at the
      Diamond Light Source, a facility dedicated to macromolecular crystallography (MX)
      with long-wavelength X-rays. The temperature is derived from the temperature
      dependent decay time constant of luminescence from a minuscule scintillation
      sensor (<0.05 mm3) located in very close proximity to the sample under test. In
      this work the underlying principle of cryogenic luminescence lifetime thermometry
      is presented, the features of the detection method and the choice of temperature
      sensor are discussed, and it is demonstrated how the temperature monitoring
      system was integrated within the viewing system of the endstation used for the
      visualization of protein crystals. The thermometry system was characterized using
      a Bi4Ge3O12 crystal scintillator that exhibits good responsivity of the decay
      time constant as a function of temperature over a wide range (8-270 K). The
      scintillation sensor was calibrated and the uncertainty of the temperature
      measurements over the primary operation temperature range of the beamline (30-150
      K) was assessed to be +/-1.6 K. It has been shown that the temperature of the
      sample holder, measured using the luminescence sensor, agrees well with the
      expected value. The technique was applied to characterize the thermal performance
      of different sample mounts that have been used in MX experiments at the I23
      beamline. The thickness of the mount is shown to have the greatest impact upon
      the temperature distribution across the sample mount. Altogether, these tests and
      findings demonstrate the usefulness of the thermometry system in highlighting the
      challenges that remain to be addressed for the in-vacuum MX experiment to become
      a reliable and indispensable tool for structural biology.

PMID- 28452756
TI  - Complex solutions under shear and pressure: a rheometer setup for X-ray
      scattering experiments.
AB  - A newly developed high-pressure rheometer for in situ X-ray scattering
      experiments is described. A commercial rheometer was modified in such a way that
      X-ray scattering experiments can be performed under different pressures and
      shear. First experiments were carried out on hyaluronan, a ubiquitous biopolymer
      that is important for different functions in the body such as articular joint
      lubrication. The data hint at a decreased electrostatic interaction at higher
      pressure, presumably due to the increase of the dielectric constant of water by
      3% and the decrease of the free volume at 300 bar.

PMID- 28452757
TI  - Caltrop particles synthesized by photochemical reaction induced by X-ray
      radiolysis.
AB  - X-ray radiolysis of a Cu(CH3COO)2 solution was observed to produce caltrop-shaped
      particles of cupric oxide (CuO, Cu2O), which were characterized using high
      resolution scanning electron microscopy and micro-Raman spectrometry. X-ray
      irradiation from a synchrotron source drove the room-temperature synthesis of
      submicrometer- and micrometer-scale cupric oxide caltrop particles from an
      aqueous Cu(CH3COO)2 solution spiked with ethanol. The size of the caltrop
      particles depended on the ratio of ethanol in the stock solution and the surface
      of the substrate. The results indicated that there were several synthetic routes
      to obtain caltrop particles, each associated with electron donation. The
      technique of X-ray irradiation enables the rapid synthesis of caltrop cupric
      oxide particles compared with conventional synthetic methods.

PMID- 28452758
TI  - Advances in testing the effect of acceleration on time dilation using a
      synchrotron Mossbauer source.
AB  - New results, additional techniques and know-how acquired, developed and employed
      in a recent HC-1898 experiment at the Nuclear Resonance Beamline ID18 of ESRF are
      presented, in the quest to explore the acceleration effect on time dilation.
      Using the specially modified Synchrotron Mossbauer Source and KB-optics together
      with a rotating single-line semicircular Mossbauer absorber on the rim of a
      specially designed rotating disk, the aim was to measure the relative spectral
      shift between the spectra of two states when the acceleration of the absorber is
      anti-parallel and parallel to the source. A control system was used for the first
      time and a method to quantify the effects of non-random vibrations on the
      spectral shift was developed. For several runs where the effect of these
      vibrations was negligible, a stable statistically significant non-zero relative
      shift was observed. This suggests the influence of acceleration on time.

PMID- 28452759
TI  - Development of picosecond time-resolved X-ray absorption spectroscopy by high
      repetition-rate laser pump/X-ray probe at Beijing Synchrotron Radiation Facility.
AB  - A new setup and commissioning of transient X-ray absorption spectroscopy are
      described, based on the high-repetition-rate laser pump/X-ray probe method, at
      the 1W2B wiggler beamline at the Beijing Synchrotron Radiation Facility. A high
      repetition-rate and high-power laser is incorporated into the setup with in-house
      built avalanche photodiodes as detectors. A simple acquisition scheme was applied
      to obtain laser-on and laser-off signals simultaneously. The capability of
      picosecond transient X-ray absorption spectroscopy measurement was demonstrated
      for a photo-induced spin-crossover iron complex in 6 mM solution with 155 kHz
      repetition rate.

PMID- 28452760
TI  - Time-resolved XAFS measurement using quick-scanning techniques at BSRF.
AB  - A new quick-scanning X-ray absorption fine-structure (QXAFS) system has been
      established on beamline 1W1B at the Beijing Synchrotron Radiation Facility. As an
      independent device, the QXAFS system can be employed by other beamlines equipped
      with a double-crystal monochromator to carry out quick energy scans and data
      acquisition. Both continuous-scan and trapezoidal-scan modes are available in
      this system to satisfy the time scale from subsecond (in the X-ray absorption
      near-edge structure region) to 1 min. Here, the trapezoidal-scan method is
      presented as being complementary to the continuous-scan method, in order to
      maintain high energy resolution and good signal-to-noise ratio. The system is
      demonstrated to be very reliable and has been combined with in situ cells to
      carry out time-resolved XAFS studies.

PMID- 28452761
TI  - Respiratory-gated KES imaging of a rat model of acute lung injury at the Canadian
      Light Source.
AB  - In this study, contrast-enhanced X-ray tomographic imaging for monitoring and
      quantifying respiratory disease in preclinical rodent models is proposed. A K
      edge imaging method has been developed at the Canadian Light Source to very
      accurately obtain measurements of the concentration of iodinated contrast agent
      in the pulmonary vasculature and inhaled xenon in the airspaces of rats. To
      compare the iodine and xenon concentration maps, a scout projection image was
      acquired to define the region of interest within the thorax for imaging and to
      ensure the same locations were imaged in each K-edge subtraction (KES)
      acquisition. A method for triggering image acquisition based on the real-time
      measurements of respiration was also developed to obtain images during end
      expiration when the lungs are stationary, in contrast to other previously
      published studies that alter the respiration to accommodate the image
      acquisition. In this study, images were obtained in mechanically ventilated
      animals using physiological parameters at the iodine K-edge in vivo and at the
      xenon K-edge post mortem (but still under mechanical ventilation). The imaging
      techniques were performed in healthy Brown Norway rats and in age-matched
      littermates that had an induced lung injury to demonstrate feasibility of the
      imaging procedures and the ability to correlate the lung injury and the
      quantitative measurements of contrast agent concentrations between the two KES
      images. The respiratory-gated KES imaging protocol can be easily adapted to image
      during any respiratory phase and is feasible for imaging disease models with
      compromised lung function.

PMID- 28452762
TI  - Radiography registration for mosaic tomography.
AB  - A hybrid method of stitching X-ray computed tomography (CT) datasets is proposed
      and the feasibility to apply the scheme in a synchrotron tomography beamline with
      micrometre resolution is shown. The proposed method enables the field of view of
      the system to be extended while spatial resolution and experimental setup remain
      unchanged. The approach relies on taking full tomographic datasets at different
      positions in a mosaic array and registering the frames using Fourier phase
      correlation and a residue-based correlation. To ensure correlation correctness,
      the limits for the shifts are determined from the experimental motor position
      readouts. The masked correlation image is then minimized to obtain the correct
      shift. The partial datasets are blended in the sinogram space to be compatible
      with common CT reconstructors. The feasibility to use the algorithm to blend the
      partial datasets in projection space is also shown, creating a new single
      dataset, and standard reconstruction algorithms are used to restore high
      resolution slices even with a small number of projections.

PMID- 28452763
TI  - Hard X-ray-induced damage on carbon-binder matrix for in situ synchrotron
      transmission X-ray microscopy tomography of Li-ion batteries.
AB  - The electrode of Li-ion batteries is required to be chemically and mechanically
      stable in the electrolyte environment for in situ monitoring by transmission X
      ray microscopy (TXM). Evidence has shown that continuous irradiation has an
      impact on the microstructure and the electrochemical performance of the
      electrode. To identify the root cause of the radiation damage, a wire-shaped
      electrode is soaked in an electrolyte in a quartz capillary and monitored using
      TXM under hard X-ray illumination. The results show that expansion of the carbon
      binder matrix by the accumulated X-ray dose is the key factor of radiation
      damage. For in situ TXM tomography, intermittent X-ray exposure during image
      capturing can be used to avoid the morphology change caused by radiation damage
      on the carbon-binder matrix.

PMID- 28452764
TI  - A high-pressure single-crystal-diffraction experimental system at 4W2 beamline of
      BSRF.
AB  - Information on the structural evolution of materials under high pressure is of
      great importance for understanding the properties of materials exhibited under
      high pressure. High-pressure powder diffraction is widely used to investigate the
      structure evolution of materials at such pressure. Unfortunately, powder
      diffraction data are usually insufficient for retrieving the atomic structures,
      with high-pressure single-crystal diffraction being more desirable for such a
      purpose. Here, a high-pressure single-crystal diffraction experimental system
      developed recently at beamline 4W2 of Beijing Synchrotron Radiation Facility
      (BSRF) is reported. The design and operation of this system are described with
      emphasis on special measures taken to allow for the special circumstance of high
      pressure single-crystal diffraction. As an illustration, a series of diffraction
      datasets were collected on a single crystal of LaB6 using this system under
      various pressures (from ambient pressure to 39.1 GPa). The quality of the
      datasets was found to be sufficient for structure solution and subsequent
      refinement.

PMID- 28452765
TI  - SUT-NANOTEC-SLRI beamline for X-ray absorption spectroscopy.
AB  - The SUT-NANOTEC-SLRI beamline was constructed in 2012 as the flagship of the SUT
      NANOTEC-SLRI Joint Research Facility for Synchrotron Utilization, co-established
      by Suranaree University of Technology (SUT), National Nanotechnology Center
      (NANOTEC) and Synchrotron Light Research Institute (SLRI). It is an intermediate
      energy X-ray absorption spectroscopy (XAS) beamline at SLRI. The beamline
      delivers an unfocused monochromatic X-ray beam of tunable photon energy (1.25-10
      keV). The maximum normal incident beam size is 13 mm (width) * 1 mm (height) with
      a photon flux of 3 * 108 to 2 * 1010 photons s-1 (100 mA)-1 varying across photon
      energies. Details of the beamline and XAS instrumentation are described. To
      demonstrate the beamline performance, K-edge XANES spectra of MgO, Al2O3, S8,
      FeS, FeSO4, Cu, Cu2O and CuO, and EXAFS spectra of Cu and CuO are presented.

PMID- 28452766
TI  - Finite-element modelling of multilayer X-ray optics.
AB  - Multilayer optical elements for hard X-rays are an attractive alternative to
      crystals whenever high photon flux and moderate energy resolution are required.
      Prediction of the temperature, strain and stress distribution in the multilayer
      optics is essential in designing the cooling scheme and optimizing geometrical
      parameters for multilayer optics. The finite-element analysis (FEA) model of the
      multilayer optics is a well established tool for doing so. Multilayers used in X
      ray optics typically consist of hundreds of periods of two types of materials.
      The thickness of one period is a few nanometers. Most multilayers are coated on
      silicon substrates of typical size 60 mm * 60 mm * 100-300 mm. The high aspect
      ratio between the size of the optics and the thickness of the multilayer (107)
      can lead to a huge number of elements for the finite-element model. For instance,
      meshing by the size of the layers will require more than 1016 elements, which is
      an impossible task for present-day computers. Conversely, meshing by the size of
      the substrate will produce a too high element shape ratio (element geometry
      width/height > 106), which causes low solution accuracy; and the number of
      elements is still very large (106). In this work, by use of ANSYS layer
      functioned elements, a thermal-structural FEA model has been implemented for
      multilayer X-ray optics. The possible number of layers that can be computed by
      presently available computers is increased considerably.

PMID- 28452767
TI  - From biofilm ecology to reactors: a focused review.
AB  - Biofilms are complex biostructures that appear on all surfaces that are regularly
      in contact with water. They are structurally complex, dynamic systems with
      attributes of primordial multicellular organisms and multifaceted ecosystems. The
      presence of biofilms may have a negative impact on the performance of various
      systems, but they can also be used beneficially for the treatment of water
      (defined herein as potable water, municipal and industrial wastewater,
      fresh/brackish/salt water bodies, groundwater) as well as in water stream-based
      biological resource recovery systems. This review addresses the following three
      topics: (1) biofilm ecology, (2) biofilm reactor technology and design, and (3)
      biofilm modeling. In so doing, it addresses the processes occurring in the
      biofilm, and how these affect and are affected by the broader biofilm system. The
      symphonic application of a suite of biological methods has led to significant
      advances in the understanding of biofilm ecology. New metabolic pathways, such as
      anaerobic ammonium oxidation (anammox) or complete ammonium oxidation (comammox)
      were first observed in biofilm reactors. The functions, properties, and
      constituents of the biofilm extracellular polymeric substance matrix are somewhat
      known, but their exact composition and role in the microbial conversion kinetics
      and biochemical transformations are still to be resolved. Biofilm grown
      microorganisms may contribute to increased metabolism of micro-pollutants.
      Several types of biofilm reactors have been used for water treatment, with
      current focus on moving bed biofilm reactors, integrated fixed-film activated
      sludge, membrane-supported biofilm reactors, and granular sludge processes. The
      control and/or beneficial use of biofilms in membrane processes is advancing.
      Biofilm models have become essential tools for fundamental biofilm research and
      biofilm reactor engineering and design. At the same time, the divergence between
      biofilm modeling and biofilm reactor modeling approaches is recognized.

PMID- 28452768
TI  - Modeling and optimization of nonylphenol removal from contaminated water media
      using a magnetic recoverable composite by artificial neural networks.
AB  - Herein, activated carbon impregnated iron oxide nanoparticles (Fe3O4/AC) were
      synthesized to determine their potentials for the adsorption of nonylphenol (NP)
      in aqueous solution with different experimental variables, namely the pH of the
      solution, contact time, adsorbent dosage and the initial NP concentration.
      Additionally, an artificial neural network system was used to find the relative
      importance of each of the aforementioned input variables on NP adsorption
      efficiency. Experimental findings indicated that the optimum solution pH for NP
      adsorption was 3.0. The equilibrium time of the adsorption process was 30 min.
      According to the results of isotherm and kinetic studies, among all applied
      models, the Liu and pseudo-first-order models showed the best fit with the
      experimental data. The pH of the solution, compared to other input variables, had
      the maximum impacts on NP adsorption efficiency. Under optimum conditions, the
      adsorption percentage decreased insignificantly from 99.6 to 92.6% after the
      fifth cycle. Also, the adsorption efficiencies of 70.7, 73.5 and 67.3% were
      observed for river water, tap water and wastewater effluent, respectively.
      Ultimately, from the findings of this study, it can be postulated that Fe3O4/AC
      nanoparticles can be recommended as a promising and novel adsorbent to remove NP
      from polluted groundwater.

PMID- 28452769
TI  - Coagulation-adsorption of reactive orange from aqueous solution by freshly formed
      magnesium hydroxide: mixing time and mechanistic study.
AB  - The utilization of magnesium hydroxide was successfully carried out to remove
      reactive orange by coagulation-adsorption from aqueous solution. The coagulation
      adsorption mechanisms and magnesium hydroxide-reactive orange floc property were
      analyzed through zeta potential, scanning electron microscope (SEM), X-ray
      diffraction and Fourier transform infrared spectroscopy (FT-IR). Flocculation
      Index was then discussed with controlled experiments using intelligent Particle
      Dispersion Analyzer (iPDA) and optimum rapid mixing time of 90 s was obtained for
      pH 12. The results of this study indicate that charge neutralization and
      adsorption are proposed to be the main coagulation mechanisms. The FT-IR spectra
      and SEM showed that reactive orange was adsorbed on the magnesium hydroxide
      surface during coagulation and adsorption. Freshly generated magnesium hydroxide
      can effectively remove reactive orange and the removal efficiency can reach 96.7%
      and 46.3% for coagulation and adsorption, respectively. Adsorption process
      accounts for 48% of the whole coagulation experiment. The removal efficiency
      decreased significantly with increasing magnesium hydroxide formation time.

PMID- 28452770
TI  - Reclaimed municipal wastewater for forage production.
AB  - This study aims to evaluate the possibility of using reclaimed municipal
      wastewater for agricultural purpose. We assessed the validity of municipal
      wastewater treatment, analyzing its chemical characteristics before and after the
      biological stabilization by pond treatment (WSP). The reclaimed municipal treated
      wastewater (TWW) was used to irrigate Cenchrus ciliaris. Experiments were carried
      out in greenhouse, from July 2013 to July 2014, comparing the effects of TWW with
      the water normally used for irrigation (tap water, TW) on the growth and
      flowering parameters of C. ciliaris. During this study, total coliforms, fecal
      coliforms, Escherichia coli, and Salmonella spp. were detected in TW, TWW, soils
      and plants under irrigation. Our results evidenced that TWW increased plant
      growth, producing taller plants with respect to TW. Total coliforms and fecal
      coliforms in TWW, TW, soils and plants were under the threshold recommended by
      the World Health Organization (WHO). Salmonella was never found in TW, TWW, or
      soil and plants irrigated with TWW. The absence of pathogens suggests that the
      pond treatment is an effective method to reclaim wastewater, lowering biochemical
      oxygen demand (BOD), chemical oxygen demand (COD) and pathogens. In this respect,
      TWW can be used as a valid alternative to freshwater for irrigation of fodder
      species.

PMID- 28452771
TI  - Thermally activated persulfate oxidation of NAPL chlorinated organic compounds:
      effect of soil composition on oxidant demand in different soil-persulfate
      systems.
AB  - This study investigates the interaction of persulfate with soil components and
      chlorinated volatile organic compounds (CVOCs), using thermally activated
      persulfate oxidation in three soil types: high sand content; high clay content;
      and paddy field soil. The effect of soil composition on the available oxidant
      demand and CVOC removal rate was evaluated. Results suggest that the treatment
      efficiency of CVOCs in soil can be ranked as follows: cis-1,2-dichloroethene >
      trichloroethylene > 1,2-dichloroethane > 1,1,1-trichloroethane. The reactions of
      soil components with persulfate, shown by the reduction in soil phase natural
      organics and mineral content, occurred in parallel with persulfate oxidation of
      CVOCs. Natural oxidant demand from the reaction of soil components with
      persulfate exerted a large relative contribution to the total oxidant demand. The
      main influencing factor in oxidant demand in paddy-soil-persulfate systems was
      natural organics, rather than mineral content as seen with sand and clay soil
      types exposed to the persulfate system. The competition between CVOCs and soil
      components for oxidation by persulfate indicates that soil composition exhibits a
      considerable influence on the available oxidant demand and CVOC removal
      efficiency. Therefore, soil composition of natural organics and mineral content
      is a critical factor in estimating the oxidation efficiency of in-situ
      remediation systems.

PMID- 28452772
TI  - Electrochemically-assisted ammonia recovery from wastewater using a floating
      electrode.
AB  - This work presents and explores a novel methodology for the removal and recovery
      of ammonia from wastewater based upon two mechanisms: electrochemical oxidation
      and a previously unreported electrochemically-assisted surface transfer
      mechanism. Recovery of ammonia is enabled by placing a porous cathodic electrode
      at the wastewater-air interface. In this configuration, the cathode creates local
      alkalinity and an electric field that draws ammonium ions towards the wastewater
      air interface, resulting in near-linear reductions of dissolved ammonium
      irrespective of concentration. This approach leads to significant ammonia
      recovery without the need for ion-exchange membranes. In addition, anodic
      reactions that simultaneously occur at depth in the wastewater induce ammonia
      oxidation in accordance with proven mechanisms. The floating electrode approach
      offers improved ammonia removal efficiency in comparison to electrooxidation.
      Trials conducted on synthetic wastewater (900 mg NH4+-N l-1) and filtered
      anaerobic centrate (560 mg NH4+-N l-1) demonstrated ammonia concentration
      decreases up to 216 mg l-1 hr-1 and 110 mg l-1 hr-1, respectively, under the
      application of 5 mA cm-2 current density. The technology would be best used to
      treat municipal and industrial wastewaters possessing high ammonia concentration,
      including anaerobic digester centrate and urine, and offers potential to assist
      in removing ammonia from environmental waters.

PMID- 28452773
TI  - A new sand adsorbent for the removal and reuse of nickel ions from aqueous
      solutions.
AB  - Nickel ions (Ni(II)) in aqueous solutions were removed by a sand adsorbent with a
      surface functionalized porous coating. The sand adsorbent has a very large
      surface area of 150 m2/g. The influence of pH, initial concentration of the
      solution, temperature, contact time and adsorbent dosage on the removal
      efficiency of the synthesized sand adsorbent toward Ni(II) in the aqueous
      solutions were studied. The results indicate that the adsorption of nickel onto
      the sand adsorbent greatly increases the pH range of 2-4 and slightly increases
      with temperature from 25 to 40  degrees C. The maximum removal efficiency and ion
      retention in per unit mass of the adsorbent were 100% and 5.78 mg/g,
      respectively, under the specified experimental conditions. The adsorption can be
      described by the pseudo-second-order kinetic model and the Freundlich adsorption
      model. The adsorbed nickel (4.24 mg/g) together with the spent adsorbent were
      successfully employed to prepare a brown glass, suggesting a new way to reutilize
      the recovered nickel from wastewater and to avoid secondary pollution caused by
      the used adsorbents.

PMID- 28452774
TI  - Electrochemical oxidation of quinoline aqueous solution on beta-PbO2 anode and
      the evolution of phytotoxicity on duckweed.
AB  - Electrochemical oxidation of quinoline on a beta-PbO2 electrode modified with
      fluoride resin and the comprehensive toxicity of intermediates formed during
      oxidation on duckweed were investigated in detail. The results showed that
      quinoline was initially hydroxylated at the C-2 and C-8 positions by hydroxyl
      radicals (.OH) electro-generated on a beta-PbO2 anode, yielding 2(1H)-quinolinone
      and 8-hydroxyquinoline, then undergoing ring cleavage to form pyridine, nicotinic
      acid, pyridine-2-carboxaldehyde and acetophenone, which were ultimately converted
      to biodegradable organic acids. NO3- was the final form of quinoline-N. The
      growth of duckweed exposed to the oxidized quinoline solution was gradually
      inhibited with the decrease in pH and the formation of intermediates. However,
      the growth inhibition of duckweed could be eliminated beyond 120 min of
      oxidation, indicating the comprehensive toxicity of the quinoline solution
      reduced when the amount of quinoline removed was above 80%. Additionally, the
      adjustment of the pH to 7.5 and the addition of nutrients to the treated
      quinoline solution before culturing duckweed could obviously alleviate the
      inhibition on duckweed. Thus, partial electrochemical degradation of quinoline
      offers a cost-effective and clean alternative for pretreatment of wastewater
      containing nitrogen-heterocyclic compounds before biological treatment. The
      duckweed test presents a simple method for assessing the comprehensive toxicity
      of intermediates.

PMID- 28452775
TI  - Removal of malachite green from aqueous solutions by electrocoagulation/peanut
      shell adsorption coupling in a batch system.
AB  - A electrocoagulation (EC)/peanut shell (PS) adsorption coupling technique was
      studied for the removal of malachite green (MG) in our present work. The addition
      of an appropriate PS dosage (5 g/L) resulted in remarkable increase in the
      removal efficiency of MG at lower current density and shorter operating time
      compared with the conventional EC process. The effect of current density, pH of
      MG solution, dosage of PS and initial concentration of MG were also investigated.
      The maximum removal efficiency of MG was 98% under optimum conditions in 5 min.
      And it was 23% higher than that in EC process. Furthermore, the unit energy
      demand (UED) and the unit electrode material demand (UEMD) were calculated and
      discussed. The results demonstrated that the EC/PS adsorption coupling method
      achieved a reduction of 94% UED and UEMD compared with EC process.

PMID- 28452776
TI  - Effect of ammonia on methane production pathways and reaction rates in acetate
      fed biogas processes.
AB  - In order to understand the correlation between ammonia and methanogenesis
      metabolism, methane production pathways and their specific rates were studied at
      total ammonium nitrogen (TAN) concentrations of 0.14-9 g/L in three methanogenic
      sludges fed with acetate, at both mesophilic and thermophilic conditions. Results
      showed that high levels of TAN had significant inhibition on methanogenesis; this
      could, however, be recovered via syntrophic acetate oxidation (SAO) coupled with
      Hydrogenotrophic Methanogenesis (HM) performed by acetate oxidizing syntrophs or
      through Acetoclastic Methanogenesis (AM) catalyzed by Methanosarcinaceae, after a
      long lag phase >50 d. Free ammonia (NH3) was the active component for this
      inhibition, of which 200 mg/L is suggested as the threshold for the pathway shift
      from AM to SAO-HM. Methane production rate via SAO-HM at TAN of 7-9 g/L was about
      5-9-fold lower than that of AM at TAN of 0.14 g/L, which was also lower than the
      rate of AM pathway recovered at TAN of 7 g/L in the incubations with a French
      mesophilic inoculum. Thermophilic condition favored the establishment of the SAO
      catalyzing microbial community, as indicated by the higher reaction rate and
      shorter lag phase. The operational strategy is thus suggested to be adjusted when
      NH3 exceeds 200 mg/L.

PMID- 28452777
TI  - Adsorption of iron(III), cobalt(II), and nickel(II) on activated carbon derived
      from Xanthoceras Sorbifolia Bunge hull: mechanisms, kinetics and influencing
      parameters.
AB  - Xanthoceras Sorbifolia Bunge hull activated carbon (XSA) was prepared and
      characterized by Brunauer-Emmett-Teller analysis, scanning electron microscopy
      and energy dispersive X-ray (EDX) spectroscopy. The ability of XSA as an
      adsorbent was investigated for the removal of the iron group ions Fe(III),
      Co(II), and Ni(II) from aqueous solution. Optimum adsorption parameters were
      determined based on the initial concentrations of the iron group ions, pH,
      adsorption temperature, and adsorption time in adsorption studies. The maximum
      monolayer adsorption capacities were 241.13 mg/g for Fe(III), 126.05 mg/g for
      Co(II), and 187.96 mg/g for Ni(II), respectively. Adsorption kinetics and
      isotherms showed that the adsorption process best fitted the nonlinear pseudo
      second-order and Langmuir models, and the affinity of the ions for XSA decreased
      as follows: Fe(III) > Ni(II) > Co(II). Regeneration studies indicated that XSA
      could be used after several consecutive adsorption/desorption cycles using HNO3.
      Fourier transform infrared and EDX spectra revealed the chemical adsorption value
      of XSA as an adsorbent for removing iron group ions from aqueous solutions.

PMID- 28452778
TI  - Impacts of onsite greywater reuse on wastewater systems.
AB  - Together with significant water savings that onsite greywater reuse (GWR) may
      provide, it may also affect the performance of urban sewer systems and wastewater
      treatment plants (WWTPs). In order to examine these effects, an integrated
      stochastic simulation system for GWR in urban areas was developed. The model
      includes stochastic generators of domestic wastewater streams and gross solids
      (GSs), a sewer network model which includes hydrodynamic simulation and a GS
      transport module, and a dynamic process model of the WWTP. The developed model
      was applied to a case study site in Israel. For the validation of the sewer
      simulator, field experiments in a real sewer segment were conducted. The paper
      presents the integration and implementation of these modules and depicts the
      results of the effects of various GWR scenarios on GS movement in sewers and on
      the performance of the WWTP.

PMID- 28452779
TI  - Which plants are needed for a French vertical-flow constructed wetland under a
      tropical climate?
AB  - Plants are essential in the functioning of constructed wetlands. When setting up
      systems in tropical areas, Phragmites australis is not always a good choice
      because of its invasiveness. In vertical-flow constructed wetlands (VFCWs) fed
      with raw wastewater, the main role of plants is their mechanical action, which
      helps prevent clogging of the deposited organic matter. Various species have
      already been used in some tropical climate studies, but generally not for such
      systems, and no attempt has been made to screen large numbers of alternative
      species. Here we describe a method to select species among a hundred studied,
      along with promising plants tested in batches, and at full scale. Species of the
      order Zingiberales showed good adaptation to the main stresses generated by
      VFCWs. They have long vegetative cycles, which may require weed growth control
      after plantation, but low harvesting frequency. Root systems with long rhizomes
      such as Heliconia psittacorum should take priority to ensure even growth and
      avoid clumps. To limit the phytosanitary risk with Musaceae (banana tree), Canna
      indica or Canna glauca are preferable. Species of the genus Cyperus also
      demonstrate good adaptation, and could be of interest, especially when a high
      stem density is required (e.g. planted sludge drying beds).

PMID- 28452780
TI  - Removal of micropollutants from municipal wastewater by graphene adsorption and
      simultaneous electrocoagulation/electrofiltration process.
AB  - In this work the optimal operating conditions for removing selected
      micropollutants (also known as emerging contaminants, ECs) from actual municipal
      wastewater by graphene adsorption (GA) and simultaneous
      electrocoagulation/electrofiltration (EC/EF) process, respectively, were first
      determined and evaluated. Then, performance and mechanisms for the removal of
      selected phthalates and pharmaceuticals from municipal wastewater simultaneously
      by the GA and EC/EF process were further assessed. ECs of concern included di-n
      butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP), acetaminophen (ACE),
      caffeine (CAF), cefalexin (CLX) and sulfamethoxazole (SMX). It was found that GA
      plus EC/EF process yielded the following removal efficiencies: DnBP, 89 +/- 2%;
      DEHP, 85 +/- 3%; ACE, 99 +/- 2%; CAF, 94 +/- 3%; CLX, 100 +/- 0%; and SMX, 98 +/-
      2%. Carbon adsorption, size exclusion, electrostatic repulsion,
      electrocoagulation, and electrofiltration were considered as the main mechanisms
      for the removal of target ECs by the integrated process indicated above.

PMID- 28452781
TI  - Biosorption of textile dye reactive blue 221 by capia pepper (Capsicum annuum L.)
      seeds.
AB  - Peppers are very important foodstuffs in the world for direct and indirect
      consumption, so they are extensively used. The seeds of these peppers are waste
      materials that are disposed of from houses and factories. To evaluate the
      performance of this biomass in the treatment of wastewaters, a study was
      conducted to remove a textile dye, reactive blue 221, which is commercially used
      in textile mills. Raw seed materials were used without any pre-treatment. The
      effects of contact time, initial concentration of dye, pH and dose of biosorbent
      were studied to determine the optimum conditions for this biomass on color
      removal from wastewaters. The optimum pH value for dye biosorption was found to
      be 2.0. At an initial dye concentration of 217 mg L-1, treatment efficiency and
      biosorption capacity were 96.7% and 95.35 mg g-1, respectively. A maximum
      biosorption capacity of 142.86 mg g-1 was also obtained. Equilibrium biosorption
      of dye by capia seeds was well described by the Langmuir isotherm with a
      correlation coefficient above 99%. The biosorption process was also successfully
      explained with the pseudo-second order kinetic model. This biomass was found to
      be effective in terms of textile dye removal from aqueous solutions.

PMID- 28452782
TI  - Sulfide emissions in sewer networks: focus on liquid to gas mass transfer
      coefficient.
AB  - H2S emission dynamics in sewers are conditioned by the mass transfer coefficient
      at the interface. This work aims at measuring the variation of the mass transfer
      coefficient with the hydraulic characteristics, with the objective of estimating
      H2S emission in gravity pipes, and collecting data to establish models
      independent of the system geometry. The ratio between the H2S and O2 mass
      transfer coefficient was assessed in an 8 L mixed reactor under different
      experimental conditions. Then, oxygen mass transfer measurements were performed
      in a 10 m long gravity pipe. The following ranges of experimental conditions were
      investigated: velocity flow [0-0.61 m.s-1], Reynolds number [0-23,333]. The
      hydrodynamic parameters at the liquid/gas interface were calculated by
      computational fluid dynamics (CFD). In the laboratory-scale reactor, the O2 mass
      transfer coefficient was found to depend on the stirring rate (rph) as follows:
      KL,O2 = 0.016 + 0.025 N3.85. A KL,H2S/KL,O2 ratio of 0.64 +/- 0.24 was found, in
      accordance with previously published data. CFD results helped in refining this
      correlation: the mass transfer coefficient depends on the local interface
      velocity ui (m.h-1): KL,O2 = 0.016 + 1.02 * 10-5 ui3.85 In the gravity pipe
      device, KL,O2 also exponentially increased with the mean flow velocity. These
      trends were found to be consistent with the increasing level of turbulence.

PMID- 28452783
TI  - Rainfall effects on inflow and infiltration in wastewater treatment systems in a
      coastal plain region.
AB  - Aging wastewater collection and treatment systems have not received as much
      attention as other forms of infrastructure, even though they are vital to public
      health, economic growth, and environmental quality. Inflow and infiltration (I&I)
      are among potentially widespread problems facing central sewage collection and
      treatment systems, posing risks of sanitary system overflows (SSOs), system
      degradation, and water quality impairment, but remain poorly quantified. Whole
      system analyses of I&I were conducted by regression analyses of system flow
      responses to rainfall and temperature for 93 wastewater treatment plants in 23
      counties in eastern North Carolina, USA, a coastal plain region with high water
      tables and generally higher rainfalls than the continental interior.
      Statistically significant flow responses to rainfall were found in 92% of these
      systems, with 2-year average I&I values exceeding 10% of rainless system flow in
      over 40% of them. The effects of rainfall, which can be intense in this coastal
      region, have region-wide implications for sewer system performance and
      environmental management. The positive association between rainfall and excessive
      I&I parallels the effects of storm water runoff on water quality, in that
      excessive I&I can also drive SSOs, thus confounding water quality protection
      efforts.

PMID- 28452784
TI  - Different erosion characteristics of sediment deposits in combined and storm
      sewers.
AB  - To investigate the different erosion patterns of sediments in combined and storm
      sewers, sediments from three separate sewer systems and two combined sewer
      systems in urban Shanghai were collected for the flushing experiments. These
      experiments were conducted with different consolidation periods and shear
      velocities. As the consolidation period increases, dissolved oxygen exhibits a
      positive effect on the microbial transformations of organic substrates. Potential
      structural changes and separations of the surface and bottom layers of sediments
      are observed. The results also reveal that the organic matter, particle size and
      moisture have different effects on the erosion resistance of sediments.
      Furthermore, illicit connections behaved as an important factor affecting the
      viscosity and static friction force of particles, which directly alter the
      erosion resistance of sewer sediments.

PMID- 28452785
TI  - Adsorption of methylene blue by using novel chitosan-g-itaconic acid/bentonite
      nanocomposite - equilibrium and kinetic study.
AB  - In this study, novel chitosan-g-itaconic acid/bentonite (CTS-g-IA/BT) and
      chitosan/bentonite (CTS/BT) nanocomposites were synthesized for adsorption of
      methylene blue (MB) from aqueous solution. The process was pH-sensitive and
      maximum sorption was obtained at pH 6 (CTS-g-IA/BT) and 7 (CTS/BT) in 76 h
      agitation time using 0.03 g of nanocomposites for 50 mL of MB solution. The
      results showed that in pH less than 6, the adsorption capacity of CTS-g-IA/BT
      nanocomposite due to the existence of IA monomer is less than that of CTS/BT
      nanocomposite. The Fourier transform infrared spectroscopy (FTIR) spectrum of CTS
      g-IA/BT revealed that both itaconic acid and BT present in the nanocomposite
      structure, and also the -OH groups of BT, -NH2 and -OH of CTS participated in
      nanocomposite formation. According to the FTIR results, a schematic diagram of
      the nanocomposite synthesis was presented. The kinetic results indicated that the
      adsorption of MB fitted well with the pseudo-second-order kinetic model. The
      equilibrium data followed Langmuir isotherm with the maximum adsorption capacity
      of 500 and 181.818 mg/g for CTS-g-IA/BT and CTS/BT nanocomposites, respectively.
      The negative values of Gibbs free energy change (DeltaG0) and the positive values
      of DeltaH0 confirmed that the adsorption process is spontaneous and endothermic.
      The positive values of DeltaS0 suggested the randomness of adsorption at
      interface.

PMID- 28452786
TI  - Accelerated anaerobic hydrolysis rates under a combination of intermittent
      aeration and anaerobic conditions.
AB  - Anaerobic hydrolysis in activated return sludge was investigated in laboratory
      scale experiments to find if intermittent aeration would accelerate anaerobic
      hydrolysis rates compared to anaerobic hydrolysis rates under strict anaerobic
      conditions. The intermittent reactors were set up in a 240 h experiment with
      intermittent aeration (3 h:3 h) in a period of 24 h followed by a subsequent
      anaerobic period of 24 h in a cycle of 48 h which was repeated five times during
      the experiment. The anaerobic reactors were kept under strict anaerobic
      conditions in the same period (240 h). Two methods for calculating hydrolysis
      rates based on soluble chemical oxygen demand were compared. Two-way analysis of
      variance with the Bonferroni post-test was performed in order to register any
      significant difference between reactors with intermittent aeration and strictly
      anaerobic conditions respectively. The experiment demonstrated a statistically
      significant difference in favor of the reactors with intermittent aeration
      showing a tendency towards accelerated anaerobic hydrolysis rates due to
      application of intermittent aeration. The conclusion of the work is thus that
      intermittent aeration applied in the activated return sludge process can improve
      the treatment capacity further in full scale applications.

PMID- 28452787
TI  - Nutrient recovery from airplane wastewater: composition, treatment and
      ecotoxicological assay.
AB  - For the 2014 World Cup and the 2016 Olympic Games, Brazil has expanded its
      airport infrastructure. This will lead to an increase in wastewater generation
      from aircrafts. This wastewater is traditionally taken from the aircrafts and
      disposed in the public sewage collection system. However, this residual water may
      have a different composition than the usual sanitary sewage. Therefore, it is
      important to study an alternative to treat this kind of wastewater. Thus, the
      objective of this study was to characterize and analyze the treatment of
      wastewater from airplane toilets through chemical precipitation for the removal
      of ammonia in the form of struvite. The airplanes' effluent showed a composition
      similar to human urine with pH 8.9, ammonia nitrogen 4,215 mg L-1, phosphorus 430
      mg L-1 and a very high acute toxicity (Vibrio fischeri). The best treatment for
      struvite formation was with pH 9.0 and molar ratio Mg:NH4:PO4 equal to
      1.5:1.0:1.0. In this case, the removal of ammonia and phosphorus achieved 97.0%
      and 95.3%, respectively. After this procedure, the toxicity by Vibrio fischeri
      decreased.

PMID- 28452788
TI  - Preparation, characterization and coagulation behaviour of polyferric magnesium
      silicate (PFMSi) coagulant.
AB  - A composite coagulant polyferric magnesium silicate (PFMSi) was synthesized by co
      polymerization. The structure and morphology of PFMSi were characterized by X-ray
      diffraction, Fourier transform infrared spectra and scanning electron microscope
      microphotographs; meanwhile, the coagulation efficiency was evaluated under
      different ratios of Fe/Si, Mg/Si, basicity ([OH]/[M] ratio), and dosage. The
      results suggested that the PFMSi coagulant shows an amorphous phase structure,
      and new chemical compounds had been formed; simultaneously, the different
      preparation conditions had major effects on coagulation performance.
      Additionally, the raw water collected from Pearl River was used as a treated
      water sample to verify the coagulation efficiency of PFMSi. Overall, it is
      suggested that PFMSi is an efficient coagulant in the removal of turbidity, UV254
      and total organic carbon, and it shows a markedly better coagulation performance
      than polymeric aluminium and non-modified coagulant. The study of coagulation
      kinetics and zeta potential showed that adsorption-bridging was the main
      mechanism for the introduction of silicon.

PMID- 28452789
TI  - Regional frequency analysis of short duration rainfall extremes using gridded
      daily rainfall data as co-variate.
AB  - A regional partial duration series (PDS) model is applied for estimation of
      intensity duration frequency relationships of extreme rainfalls in Denmark. The
      model uses generalised least squares regression to relate the PDS parameters to
      gridded rainfall statistics from a dense network of rain gauges with daily
      measurements. The Poisson rate is positively correlated to the mean annual
      precipitation for all durations considered (1 min to 48 hours). The mean
      intensity can be assumed constant over Denmark for durations up to 1 hour. For
      durations larger than 1 hour, the mean intensity is significantly correlated to
      the mean extreme daily precipitation. A Generalised Pareto distribution with a
      regional constant shape parameter is adopted. Compared to previous regional
      studies in Denmark, a general increase in extreme rainfall intensity for
      durations up to 1 hour is found, whereas for larger durations both increases and
      decreases are seen. A subsample analysis is conducted to evaluate the impacts of
      non-stationarities in the rainfall data. The regional model includes the non
      stationarities as an additional source of uncertainty, together with sampling
      uncertainty and uncertainty caused by spatial variability.

PMID- 28452791
TI  - Corrigendum: Water Science and Technology 74 (3), 714-721: High performance of
      nitrogen and phosphorus removal in an electrolysis-integrated biofilter, Y. Gao,
      Y. W. Xie, Q. Zhang, Y. X. Yu and L. Y. Yang, doi: 10.2166/wst.2016.190.

PMID- 28452790
TI  - The impact of anionic polyacrylamide (APAM) on ultrafiltration efficiency in
      flocculation-ultrafiltration process.
AB  - With the purpose of improving the ultrafiltration (UF) efficiency, anionic
      polyacrylamide (APAM) has been used as a coagulant aid in the flocculation-UF
      process. In this study, the impact of APAM on UF efficiency has been investigated
      with regard to membrane fouling, membrane cleaning and effluent quality. The
      results indicated that the optimal dosage of APAM had positive impacts on
      membrane fouling control, membrane cleaning and effluent quality. According to
      the flux decline curve, scanning electron microscopy and contact angle
      characterization, the optimal dosage of APAM was determined to be 0.1 mg/L
      coupled with 2 mg/L (as Al3+) poly-aluminium chloride. Under this optimal
      condition, membrane fouling can be mitigated because of the formation of a porous
      and hydrophilic fouling layer. APAM in the fouling layer can improve the chemical
      cleaning efficiency of 0.5% NaOH due to the disintegration of the fouling layer
      when APAM is dissolved under strong alkaline conditions. Furthermore, with the
      addition of APAM in the flocculation-UF process, more active adsorption sites can
      be formed in the flocs as well as the membrane fouling layer, thus more
      antipyrine molecules in the raw water can be adsorbed and removed in the
      flocculation-UF process.

PMID- 28452792
TI  - Epidermolysis Bullosa Acquisita (Brunsting-Perry Pemphigoid Variant) Localized to
      the Face and Diagnosed With Antigen Identification Using Skin Deficient in Type
      VII Collagen.
AB  - Brunsting-Perry pemphigoid is defined as an autoimmune vesiculobullous eruption
      typically localized on the head and neck region with minimal or no mucosal
      involvement. The disease tends to run a chronic and recurrent course with
      residual scarring. Histological features are characterized by subepidermal bullae
      and linear IgG deposits at the dermo-epidermal junction. We report a case of a 46
      year-old lady who presented with typical features of Brunsting-Perry pemphigoid.
      Autoantibodies to type VII collagen were identified by using recessive dystrophic
      epidermolysis bullosa skin which lacks type VII collagen in an indirect
      immunofluorescence assay. As a result, we diagnosed our patient as having the
      Brunsting-Perry pemphigoid variant of epidermolysis bullosa acquisita (EBA). This
      finding led us to review the literature on target antigens in Brunsting-Perry
      pemphigoid. Only 11 out of the 58 cases reported to date had target antigens
      identified. Interestingly, type VII collagen was the second most common target
      antigen/autoantibody (4 cases) detected after BP180 (5 cases). However, 2 further
      cases of EBA localized to the face with typical features of Brunsting-Perry
      pemphigoid were found in the literature. Although the target antigens are
      heterogeneous in Brunsting-Perry pemphigoid, a significant number of cases
      represent a clinical presentation of localized EBA.

PMID- 28452793
TI  - Painful Pustules on Hands and Feet With Acute Hepatitis: Answer.

PMID- 28452794
TI  - Cutaneous Presentation of a Testicular Germ Cell Tumor With Seminomatous
      Differentiation.

PMID- 28452795
TI  - Association Between Allogeneic Blood Transfusion and Postoperative Infection in
      Major Spine Surgery.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objective of this study
      is to compare the incidence of infection in patients who do and do not receive
      blood transfusions in major deformity surgery (>8 levels). SUMMARY OF BACKGROUND
      DATA: Postoperative infections increase morbidity and mortality rates in spine
      surgery and generate additional costs for the health care system. It has been
      proposed that blood transfusions increase the risk of wound infection, urinary
      tract infection, pneumonia, and sepsis. METHODS: A total of 56 patients met the
      study criteria, receiving spine surgery involving the fusion of 8 levels or more.
      Patient-specific characteristics, starting and ending hematocrits, number of
      units transfused and infections including urinary tract infection, wound
      infection, pneumonia, and sepsis were documented. Differences in infection risk
      between those who did and did not undergo a transfusion and their 95% confidence
      intervals were calculated. RESULTS: Groups were similar with respect to baseline
      and surgical characteristics except for smoking status, operative time, estimated
      blood loss, and ending hematocrit. The overall infection rate was greater in
      patients who underwent transfusion than those who did not (36% vs. 10%; P=0.03).
      Wound infections (n=5) were only observed in those who underwent a transfusion.
      Smokers were more likely to receive a transfusion and more likely to experience
      infection. A stratified analysis demonstrated an increased risk of infection
      associated with transfusion; however, the risk was greater in smokers, suggesting
      the effect of transfusion on infection could be modified by smoking. Patients
      undergoing transfusion experienced a significantly longer hospital stay (P=0.01).
      CONCLUSIONS: Allogeneic red blood cell transfusion in major spine surgery could
      be a risk factor for postoperative infection. This increased risk seems to be
      magnified in those who smoke. Further studies are warranted, and risks of blood
      loss and transfusion-related complications in smokers also potentially merit
      exploration. LEVEL OF EVIDENCE: Level 3.

PMID- 28452796
TI  - UK audit of quantitative thyroid uptake imaging.
AB  - AIM: A national audit of quantitative thyroid uptake imaging was conducted by the
      Nuclear Medicine Software Quality Group of the Institute of Physics and
      Engineering in Medicine in 2014/2015. The aims of the audit were to measure and
      assess the variability in thyroid uptake results across the UK and to compare
      local protocols with British Nuclear Medicine Society (BNMS) guidelines.
      PARTICIPANTS AND METHODS: Participants were invited through a combination of
      emails on a public mailbase and targeted invitations from regional co-ordinators.
      All participants were given a set of images from which to calculate quantitative
      measures and a spreadsheet for capturing results. The image data consisted of two
      sets of 10 anterior thyroid images, half of which were acquired after
      administration of Tc-pertechnetate and the other half after administration of I
      iodide. Images of the administration syringes or thyroid phantoms were also
      included. RESULTS: In total, 54 participants responded to the audit. The median
      number of scans conducted per year was 50. A majority of centres had at least one
      noncompliance in comparison with BNMS guidelines. Of most concern was the
      widespread lack of injection-site imaging. Quantitative results showed that both
      intersite and intrasite variability were low for the Tc dataset. The coefficient
      of quartile deviation was between 0.03 and 0.13 for measurements of overall
      percentage uptake. Although the number of returns for the I dataset was smaller,
      the level of variability between participants was greater (the coefficient of
      quartile deviation was between 0.17 and 0.25). CONCLUSION: A UK-wide audit showed
      that thyroid uptake imaging is still a common test in the UK. It was found that
      most centres do not adhere to all aspects of the BNMS practice guidelines but
      that quantitative results are reasonably consistent for Tc-based scans.

PMID- 28452797
TI  - A national survey of computed tomography doses in hybrid PET-CT and SPECT-CT
      examinations in the UK.
AB  - OBJECTIVES: The aim of this study was to conduct a nationwide survey of computed
      tomography (CT) doses for a wide range of PET-CT and single photon emission
      computed tomography-computed tomography (SPECT-CT) imaging procedures, with the
      aim of generating proposed UK national diagnostic reference levels (NDRLs).
      METHODS: CT protocol and dosimetry data for three PET-CT and seven SPECT-CT
      examinations were gathered from centres across the UK. Data were divided
      according to CT purpose (attenuation correction, localization or diagnostic) and
      third quartile values of scanner average dose metrics were used to generate
      suggested NDRLs for a range of examination and CT purpose combinations.
      Achievable doses were also established from the median of the dose distributions.
      RESULTS: Data were obtained from 47 centres, allowing suggested NDRLs to be
      produced for fluorine-18-fluorodeoxyglucose half-body PET-CT, and parathyroid,
      post-thyroid ablation, meta-iodobenzylguanidine/octreotide, cardiac and bone
      SPECT-CT examinations.Variations in dose of up to a factor of 35 were observed
      for a given examination/CT purpose combination. For fluorine-18
      fluorodeoxyglucose half-body PET-CT examination dose levels for the three CT
      purposes overlapped, which highlights the variability in the way in which CT
      purposes are interpreted across the UK. This lack of standardization is believed
      to be the largest contributor to the dose variations that were observed. The
      survey highlighted the need for targeted optimization work in many centres.
      CONCLUSION: Suggested UK NDRLs and achievable doses for six common PET-CT and
      SPECT-CT examinations have been established as a result of this study.

PMID- 28452798
TI  - Familial craniofacial abnormality and polymicrogyria associated with a
      microdeletion affecting the NFIA gene.

PMID- 28452799
TI  - Nurses Supporting Family Caregivers.
AB  - Caregivers need more guidance from nurses to perform increasingly complex tasks.

PMID- 28452800
TI  - Managing Complex Medication Regimens.
AB  - : This article is the first in a series, Supporting Family Caregivers: No Longer
      Home Alone, published in collaboration with the AARP Public Policy Institute.
      Results of focus groups conducted as part of the AARP Public Policy Institute's
      No Longer Home Alone video project supported evidence that family caregivers
      aren't being given the information they need to manage the complex care regimens
      of their family members. This series of articles and accompanying videos aims to
      help nurses provide caregivers with the tools they need to manage their family
      member's medications. Each article explains the principles nurses should consider
      and reinforce with caregivers and is accompanied by a video for the caregiver to
      watch. The first video can be accessed at http://links.lww.com/AJN/A74.

PMID- 28452801
TI  - Administration of Subcutaneous Injections.
AB  - : This article is the second in a series, Supporting Family Caregivers: No Longer
      Home Alone, published in collaboration with the AARP Public Policy Institute.
      Results of focus groups conducted as part of the AARP Public Policy Institute's
      No Longer Home Alone video project supported evidence that family caregivers
      aren't being given the information they need to manage the complex care regimens
      of their family members. This series of articles and accompanying videos aims to
      help nurses provide caregivers with the tools they need to manage their family
      member's medications. Each article explains the principles nurses should consider
      and reinforce with caregivers and is accompanied by a video for the caregiver to
      watch. The second video can be accessed at http://links.lww.com/AJN/A75.

PMID- 28452802
TI  - Teaching Caregivers to Administer Eye Drops, Transdermal Patches, and
      Suppositories.
AB  - : This article is the third in a series, Supporting Family Caregivers: No Longer
      Home Alone, published in collaboration with the AARP Public Policy Institute.
      Results of focus groups conducted as part of the AARP Public Policy Institute's
      No Longer Home Alone video project supported evidence that family caregivers
      aren't being given the information they need to manage the complex care regimens
      of their family members. This series of articles and accompanying videos aims to
      help nurses provide caregivers with the tools they need to manage their family
      member's medications. Each article explains the principles nurses should consider
      and reinforce with caregivers and is accompanied by a video for the caregiver to
      watch. The third video can be accessed at http://links.lww.com/AJN/A76.

PMID- 28452803
TI  - Medication Management for People with Dementia.
AB  - : This article is the fourth in a series, Supporting Family Caregivers: No Longer
      Home Alone, published in collaboration with the AARP Public Policy Institute.
      Results of focus groups conducted as part of the AARP Public Policy Institute's
      No Longer Home Alone video project supported evidence that family caregivers
      aren't being given the information they need to manage the complex care regimens
      of their family members. This series of articles and accompanying videos aims to
      help nurses provide caregivers with the tools they need to manage their family
      member's medications. Each article explains the principles nurses should consider
      and reinforce with caregivers and is accompanied by a video for the caregiver to
      watch. The fourth video can be accessed at http://links.lww.com/AJN/A78.

PMID- 28452804
TI  - Discharge Planning and Teaching.
AB  - : This article is the fifth in a series, Supporting Family Caregivers: No Longer
      Home Alone, published in collaboration with the AARP Public Policy Institute.
      Results of focus groups conducted as part of the AARP Public Policy Institute's
      No Longer Home Alone video project supported evidence that family caregivers
      aren't being given the information they need to manage the complex care regimens
      of their family members. This series of articles and accompanying videos aims to
      help nurses provide caregivers with the tools they need to manage their family
      member's medications. Each article explains the principles nurses should consider
      and reinforce with caregivers and is accompanied by a video for the caregiver to
      watch. The fifth video can be accessed at http://links.lww.com/AJN/A79.

PMID- 28452806
TI  - Perioperative Steroid Management: Approaches Based on Current Evidence.

PMID- 28452807
TI  - Oxytocin inhibits head and neck squamous cell carcinoma cell migration by early
      growth response-1 upregulation.
AB  - The effect of oxytocin (OXT) on cancer invasion is controversial. Few studies
      have examined the effect of early growth response-1 (EGR1) on the invasion of
      head and neck squamous cell carcinoma (HNSCC). Here, we evaluated how EGR1
      affects HNSCC cell migration through the molecular mechanism of OXT in exerting
      anti-invasion activity. Matrigel invasion and wound-healing assays were used to
      measure the in-vitro cell migration. The molecular mechanism of OXT was assessed
      by knockdown or overexpression of EGR1 in HNSCC cells. Three-dimensional (3-D)
      spheroids formation, followed by the image analysis for quantification was
      performed. OXT at 500 nmol/l increased mRNA and protein expression of E-cadherin
      without cytotoxicity. OXT upregulated mRNA and protein expression of EGR1 in 6 h.
      p53, phosphatase and tensin, and p21 expression was increased in an EGR1
      dependent manner with OXT treatment. In addition, OXT significantly downregulated
      3-D spheroids' formation according to spheroids' number and size. Our data showed
      that OXT downregulated HNSCC cell migration by EGR1 upregulation. OXT inhibited
      spheroids' formation of HNSCC cells under 3-D culture conditions.

PMID- 28452808
TI  - Specific Location of Disc Hemorrhage is Linked to Nerve Fiber Layer Defects.
AB  - PURPOSE: To investigate the relationship between retinal nerve fiber layer (RNFL)
      defects and the quadrant and proximal location of disc hemorrhages (DHs) in a
      large population examined for health screening. METHODS: A total of 168,044
      subjects older than 20 years underwent a single screening ophthalmic examination
      with color fundus photography as part of a comprehensive health screening
      program. The presence and location of DHs and RNFL defects were assessed. The DH
      locations were defined according to the quadrant location (inferotemporal,
      superotemporal, inferonasal, or superonasal) and the most proximal end of DHs
      relative to the disc center (cup base, cup margin, disc rim, or extrapapillary
      region). Using these two location descriptors as independent variables, a
      logistic regression analysis was conducted to explore the effects of DH location
      on RNFL defects. RESULTS: Two hundred twenty-six eyes had DH and 120 (53.1%) of
      them had RNFL defects. After adjusting for proximal location, DHs located in the
      inferotemporal quadrant accompanied RFNL defects 12 times more frequently than
      those in the superonasal quadrant (odds ratio [OR], 11.81; P = .004). Conversely,
      after adjusting for quadrant location, the ORs for an associated RNFL defect were
      3.73 (P < .001), 16.54 (P < .001), and 8.91 (P = .002) for DHs with the proximal
      end at the disc rim, cup margin, and cup base, respectively. CONCLUSIONS: Among
      the four quadrants and four proximal locations, DHs were identified most
      frequently in the inferotemporal quadrant and outside the disc, respectively.
      Some DH locations, such as the inferotemporal quadrant and the cup margin, were
      associated with RNFL defects, whereas others were not.

PMID- 28452809
TI  - Emergency care systems: increasing pressures but little sustainability.

PMID- 28452810
TI  - Severe pulmonary embolism managed with high-flow nasal cannula oxygen therapy.

PMID- 28452811
TI  - Emergency management of cardiac tamponade complicating percutaneous coronary
      intervention using intermittent pericardial drainage and retransfusion during
      interhospital transport.

PMID- 28452812
TI  - Genetic and environmental factors significant for the presentation and
      development of inflammatory bowel disease.
AB  - OBJECTIVES: The aim of the study was to evaluate associations between
      inflammatory bowel disease (IBD) presentation and variants in NOD2, TLR4, TNF
      alpha, IL-6, IL-1beta, and IL-RN genes in order to identify possible
      environmental factors that may affect IBD occurrence, investigate potential
      predictors for surgical treatment of IBD, and correlate the presence of
      granulomas in biopsy specimens with clinical characteristics of Crohn's disease
      (CD) patients. PATIENTS AND METHODS: We genotyped 167 IBD patients using PCR
      based methodology and tested for disease genotype-phenotype associations.
      RESULTS: In CD patients ileal localization of disease was more frequent in NOD2
      variant carriers. Ileal CD was associated with IL-6 GC+CC genotypes, identifying
      C allele as a possible marker of increased risk for ileal CD. In CD patients a
      positive family history for IBD was related to earlier onset of disease, higher
      risk for CD-related surgery, and appendectomy. CD patients who are TLR4 299Gly
      carriers are at higher risk for surgery at onset of the disease compared with
      TLR4 299Asp variant carriers. The presence of granuloma in biopsy specimens was
      more frequent in patients in whom a diagnosis of CD was made during emergency
      surgery. Multivariate analysis showed that CD carriers of the 299Gly allele had a
      4.6-fold higher risk for emergency surgery before CD diagnosis is established
      compared with noncarriers, suggesting an aggressive disease course. Granuloma in
      endoscopic biopsies is detected 5.4-fold more frequently in patients treated
      surgically at the time of diagnosis. CONCLUSION: Genetic variants together with
      epidemiological and clinical data of IBD patients could potentially be used as
      predictors of the disease course.

PMID- 28452813
TI  - Duodenal histopathology and laboratory deficiencies related to bone metabolism in
      coeliac disease.
AB  - OBJECTIVES: Coeliac disease (CD) is a chronic immune-mediated small intestine
      enteropathy precipitated by gluten in genetically predisposed individuals. Adult
      presentation is often atypical and malabsorption of vitamins and minerals is
      common, with a consequent disturbance of bone metabolism. We aim to evaluate
      laboratory deficiencies related to bone metabolism and the relationship between
      severity of histological damage and degree of bone mass loss at diagnosis of CD.
      MATERIALS AND METHODS: A retrospective cross-sectional study of 176 adult coeliac
      patients was carried out. All patients fulfilled the histopathological criteria
      for CD. Biochemical data were analysed (calcium/phosphate/alkaline
      phosphatase/vitamin D/parathormone). Duodenal histology was classified according
      to the Marsh classification. Bone mass density (BMD) at the lumbar and femoral
      regions measured by dual X-ray absorptiometry. A P-value of less than 0.05 was
      considered significant. RESULTS: No correlation was found between the presence of
      gastrointestinal symptoms and the Marsh histopathological stage (P>0.05). Vitamin
      D deficiency was most common (44.5%), whereas only 5.7% had hypocalcaemia.
      Calcium was lower (P<0.05) and parathormone was higher (P=0.01) in patients with
      Marsh III. These patients had lower lumbar T-score (P<0.05). Although low BMD
      occurred in all age groups, most osteoporotic patients were aged 45-49 years
      (81.8%). A multiple regression analysis showed that the Marsh histopathological
      stage could be a predictor of lower lumbar BMD (r=0.322, B=-1.146, P<0.05).
      CONCLUSION: Laboratory deficiencies and decreased BMD could be severe and
      unrelated to the presence of gastrointestinal symptoms. At diagnosis, the Marsh
      histopathological stage could predict the occurrence of low BMD, which carries a
      risk of developing into osteoporosis. In coeliac patients older than 30 years,
      evaluation of bone biomarkers and dual X-ray absorptiometry examination should be
      considered.

PMID- 28452815
TI  - Pediatric Preoperative Assessment: Six Million Missed Opportunities for Childhood
      Obesity Education.

PMID- 28452816
TI  - Tetrodotoxin, Epinephrine, and Chemical Permeation Enhancer Combinations in
      Peripheral Nerve Blockade.
AB  - BACKGROUND: Chemical permeation enhancers (CPEs) have the potential to improve
      nerve blockade by site 1 sodium channel blockers such as tetrodotoxin (TTX).
      Here, we investigated the efficacy and toxicity of CPE-enhanced nerve blockade
      across a range of TTX concentrations using 2 CPEs (sodium octyl sulfate and octyl
      trimethyl ammonium bromide). We also tested the hypothesis that CPEs could be
      used to reduce the concentrations of TTX and/or of a second adjuvant drug (in
      this case, epinephrine) needed to achieve prolonged local anesthesia METHODS::
      Sprague-Dawley rats were injected at the sciatic nerve with combinations of TTX
      and CPEs, with and without epinephrine. Sensory and motor nerve blockade were
      assessed using a modified hot plate test and a weight-bearing test, respectively.
      Systemic and local toxicities of the different combinations were assessed.
      RESULTS: Addition of increasing concentrations of TTX to fixed concentrations of
      CPEs produced a marked concentration-dependent improvement in the rate of
      successful nerve blocks and in nerve block duration. CPEs did not affect systemic
      toxicity. At some concentrations, the addition of sodium octyl sulfate increased
      the duration of block from TTX plus epinephrine, and epinephrine increased that
      from TTX plus CPEs. The addition of epinephrine did not cause an increase in
      local toxicity, and it markedly reduced systemic toxicity. CONCLUSIONS: CPEs can
      prolong the duration of nerve blockade across a range of concentrations of TTX.
      CPEs could also be used to reduce the concentration of epinephrine needed to
      achieve a given degree of nerve block. CPEs may be useful in enhancing nerve
      blockade from site 1 sodium channel blockers.

PMID- 28452817
TI  - Measuring and Improving the Quality of Preprocedural Assessments.
AB  - BACKGROUND: Preprocedural assessments are used by anesthesia providers to
      optimize perioperative care for patients undergoing invasive procedures. When
      these assessments are performed in advance by providers who are not caring for
      the patient during the procedure, there is an additional layer of complexity in
      ensuring that the workup meets the needs of the primary anesthesia care team. In
      this study, anesthesia providers were asked to rate the quality of preprocedural
      assessments prepared by other providers to evaluate anesthesia care team
      satisfaction. METHODS: Quality ratings for preprocedural assessments were
      collected from anesthesia providers on the day of surgery using an electronic
      quality assurance tool from January 9, 2014 to October 21, 2014. Users could rate
      assessments as "exemplary," "satisfactory," or "unsatisfactory." Free text
      comments could be entered for any of the quality ratings chosen. A reviewer
      trained in clinical anesthesia categorized all comments as "positive,"
      "constructive," or "neutral" and conducted in-depth chart reviews triggered by 67
      "constructive" comments submitted during the first 3 months of data collection to
      further subcategorize perceived deficiencies in the preprocedural assessments. In
      May 2014, providers were asked to participate in a midpoint survey and provide
      general feedback about the preprocedural process and evaluations. RESULTS: 37,611
      procedures requiring anesthesia were analyzed. Of the 17,522 (46.6%) cases with a
      rated preprocedural assessment, anesthesia providers rated 3828 (21.8%) as
      "exemplary," 13,454 (76.8%) as "satisfactory," and 240 (1.4%) as
      "unsatisfactory." The monthly proportion of "unsatisfactory" ratings ranged from
      3.1% to 0% over the study period, whereas the midpoint survey showed that
      anesthesia providers estimated that the number of unsatisfactory evaluations was
      11.5%. Preprocedural evaluations performed on inpatients received significantly
      better ratings than evaluations performed on outpatients by the preadmission
      testing clinic or phone program (P < .0001). The most common reason given for
      "unsatisfactory" ratings was a perception of "missing information" (49.2%). Chart
      reviews revealed that inadequate documentation was in reality the most common
      deficiency in preprocedural evaluations (35 of 67 reviews, 52.2%). CONCLUSIONS:
      The overwhelming majority of preprocedural assessments performed at our
      institution were considered satisfactory or exemplary by day-of-surgery
      anesthesia providers. This was demonstrated by both the case-by-case ratings and
      midpoint survey. However, the perceived frequency of "unsatisfactory" evaluations
      was worse when providers were asked to reflect on the quality of preprocedural
      evaluations generally versus rate them individually. Analysis of comments left by
      providers allowed us to identify specific and actionable areas for improvement.
      This method can be used by other institutions to identify systemic deficiencies
      in the preprocedural evaluation process.

PMID- 28452818
TI  - The Need for a Global Perspective on Task-Sharing in Anesthesia.

PMID- 28452819
TI  - Optimizing Anesthesia-Related Waste Disposal in the Operating Room: A Brief
      Report.
AB  - Misappropriation of noncontaminated waste into regulated medical waste (RMW)
      containers is a source of added expense to health care facilities. The operating
      room is a significant contributor to RMW waste production. This study sought to
      determine whether disposing of anesthesia-related waste in standard waste
      receptacles before patient entry into the operating room would produce a
      reduction in RMW. A median of 0.35 kg of waste was collected from 51 cases
      sampled, with a potential annual reduction of 13,800 kg of RMW to the host
      institution, and a cost savings of $2200.

PMID- 28452820
TI  - Left Main Coronary Artery Dissection During Aortic Valve Replacement.

PMID- 28452821
TI  - Analysis of Production, Impact, and Scientific Collaboration on Difficult Airway
      Through the Web of Science and Scopus (1981-2013).
AB  - BACKGROUND: Bibliometrics, the statistical analysis of written publications, is
      an increasingly popular approach to the assessment of scientific activity.
      Bibliometrics allows researchers to assess the impact of a field, or research
      area, and has been used to make decisions regarding research funding. Through
      bibliometric analysis, we hypothesized that a bibliometric analysis of difficult
      airway research would demonstrate a growth in authors and articles over time.
      METHODS: Using the Web of Science (WoS) and Scopus databases, we conducted a
      search of published manuscripts on the difficult airway from January 1981 to
      December 2013. After removal of duplicates, we identified 2412 articles. We then
      analyzed the articles as a group to assess indicators of productivity,
      collaboration, and impact over this time period. RESULTS: We found an increase in
      productivity over the study period, with 37 manuscripts published between 1981
      and 1990, and 1268 between 2001 and 2010 (P < .001). The difficult airway papers
      growth rate was bigger than that of anesthesiology research in general, with CAGR
      (cumulative average growth rate) since 1999 for difficult airway >9% for both WoS
      and Scopus, and CAGR for anesthesiology as a whole =0.64% in WoS, and =3.30% in
      Scopus. Furthermore, we found a positive correlation between the number of papers
      published per author and the number of coauthored manuscripts (P < .001). We also
      found an increase in the number of coauthored manuscripts, in international
      cooperation between institutions, and in the number of citations for each
      manuscript. For any author, we also identified a positive relationship between
      the number of citations per manuscript and the number of papers published (P <
      .001). CONCLUSIONS: We found a greater increase over time in the number of
      difficult airway manuscripts than for anesthesiology research overall. We found
      that collaboration between authors increases their impact, and that an increase
      in collaboration increases citation rates. Publishing in English and in certain
      journals, and collaborating with certain authors and institutions, increases the
      visibility of manuscripts published on this subject.

PMID- 28452822
TI  - A Prospective, Randomized, Clinical Trial on the Effects of a Valveless Trocar on
      Respiratory Mechanics During Robotic Radical Cystectomy: A Pilot Study.
AB  - BACKGROUND: Prolonged pneumoperitoneum and Trendelenburg positioning for robot
      assisted radical cystectomy (RARC) are essential for optimizing visualization of
      the operative field, although they worsen hemodynamic and respiratory function.
      Our hypothesis is that the use of a valveless trocar (VT) may improve respiratory
      mechanics. METHODS: In this prospective, 2-arm parallel trial, patients ASA II to
      III undergoing RARC were randomly assigned into 2 groups: in the VT group, the
      capnoperitoneum was maintained with a VT; in the control group, the
      capnoperitoneum was maintained with a standard trocar (ST group). Inspiratory
      plateau pressure (Pplat), static compliance (Cstat), minute volume (MV), tidal
      volume (Vt), and carbon dioxide (CO2) elimination rate were recorded at these
      times: 15 minutes after anesthesia induction (T0), 10 minutes (T1) and 60 minutes
      (T2) after first robot docking, 10 minutes before first undocking (T3), 10
      minutes (T4) and 60 minutes (T5) after second docking, 10 minutes before second
      undocking (T6), and 10 minutes before extubation (T7). The primary end point of
      the study was the assessment of Pplat mean value from T1 to T6. RESULTS: A total
      of 56 patients were evaluated: 28 patients in the VT group and 28 in the ST
      group. VT group had lower Pplat (means and standard error, VT group 30 [0.66]
      versus ST group 34 [0.66] cm H2O, with estimated mean difference and 95%
      confidence interval, -4.1 [-5.9 to -2.2], P < .01), lower MV (means and standard
      error, VT group 8.2 [0.22] versus ST group 9.8 [0.21] L min, P < .01), lower CO2
      elimination rate (means and standard error, VT group 4.2 [0.25] versus ST group
      5.4 [0.24] mL kg min, P < .01), lower end-tidal CO2 (ETCO2) (means and standard
      error, VT group 28.8 [0.48] versus ST group 31.3 [0.46] mm Hg, P < .01), and
      higher Cstat (means and standard error, VT group 26 [0.9] versus ST group 22.1
      [0.9] mL cm H2O, P < .01). Both groups had similar Vt (P = .24). CONCLUSIONS:
      During RARC, use of a VT was associated with a significantly lower Pplat and
      improvement in other respiratory parameters.

PMID- 28452823
TI  - Arterial Pressure and the Rate of Elimination of Crystalloid Fluid.
AB  - Excretion of crystalloid fluid is slow during general anesthesia. The
      distribution and elimination of buffered Ringer's solution were analyzed to
      determine whether the rate of elimination correlates with a hemodynamic factor,
      consciousness, patient posture, or the type of general anesthesia. Data were
      derived from 4 separately published studies in which 30 volunteers and 48
      anesthetized patients had received 0.833 (1 series 0.667) mL/kg/min of lactated
      or acetated Ringer's solution over 30 minutes. Frequent measurements of the blood
      hemoglobin and mean urinary excretion were used as input in a kinetic analysis
      according to a 2-volume model and covariates, using microconstants and mixed
      effects modeling software.The results show that rate of elimination of
      crystalloid fluid decreased with the mean arterial pressure (MAP) and patient
      age, but was unaffected by consciousness and inhalational or intravenous
      anesthesia. The elimination rate constant was 6.5 (95% confidence interval, 5.2
      7.9) * 10 * (MAP/mean MAP) * (Age/mean Age). The mean MAP for the 2108 data
      points was 81.3 mm Hg and the mean age was 40 years. The central fluid space that
      was expanded by infused fluid (Vc, plasma volume) increased with body weight but
      decreased with general anesthesia and with reductions of MAP.Simulations revealed
      a more than 10-fold difference in the excreted fluid volume after a theoretical
      30-minute infusion, depending on whether the MAP was 50 or 100 mm Hg.In
      conclusion, the rate of elimination of crystalloid fluid decreased in proportion
      to MAP but was independent of general anesthesia and moderate-sized surgery.

PMID- 28452824
TI  - Analysis of shared homozygosity regions in Saudi siblings with attention deficit
      hyperactivity disorder.
AB  - AIM: Genetic and clinical complexities are common features of most psychiatric
      illnesses that pose a major obstacle in risk-gene identification. Attention
      deficit hyperactivity disorder (ADHD) is the most prevalent child-onset
      psychiatric illness, with high heritability. Over the past decade, numerous
      genetic studies utilizing various approaches, such as genome-wide association,
      candidate-gene association, and linkage analysis, have identified a multitude of
      candidate loci/genes. However, such studies have yielded diverse findings that
      are rarely reproduced, indicating that other genetic determinants have not been
      discovered yet. In this study, we carried out sib-pair analysis on seven
      multiplex families with ADHD from Saudi Arabia. We aimed to identify the
      candidate chromosomal regions and genes linked to the disease. PATIENTS AND
      METHODS: A total of 41 individuals from multiplex families were analyzed for
      shared regions of homozygosity. Genes within these regions were prioritized
      according to their potential relevance to ADHD. RESULTS: We identified multiple
      genomic regions spanning different chromosomes to be shared among affected
      members of each family; these included chromosomes 3, 5, 6, 7, 8, 9, 10, 13, 17,
      and 18. We also found specific regions on chromosomes 8 and 17 to be shared
      between affected individuals from more than one family. Among the genes present
      in the regions reported here were involved in neurotransmission (GRM3, SIGMAR1,
      CHAT, and SLC18A3) and members of the HLA gene family (HLA-A, HLA-DPA1, and
      MICC). CONCLUSION: The candidate regions identified in this study highlight the
      genetic diversity of ADHD. Upon further investigation, these loci may reveal
      candidate genes that enclose variants associated with ADHD. Although most ADHD
      studies were conducted in other populations, our study provides insight from an
      understudied, ethnically interesting population.

PMID- 28452826
TI  - The Author Responds.

PMID- 28452827
TI  - Re: Integrating Complex Systems Thinking into Epidemiologic Research.

PMID- 28452825
TI  - Joint Impact of Early Life Adversity and COMT Val158Met (rs4680) Genotypes on the
      Adult Cortisol Response to Psychological Stress.
AB  - OBJECTIVE: Exposure to stress during critical periods of development can diminish
      stress reactivity by the hypothalamic-pituitary-adrenocortical axis. Genetic
      characteristics may further modify this effect of early adversity, leading to a
      gene by environment (G * E) interaction on stress reactivity in adulthood. Val
      allele carriers of a common polymorphism of the COMT gene (Val158Met, rs4680)
      have rapid removal of catecholamines in the prefrontal cortex, limbic system, and
      reward centers. Carriers of the Val and Met alleles may therefore respond
      differently to the environment and differ in the long-term impact of exposure to
      early life adversity (ELA). METHODS: We measured saliva cortisol reactivity to
      public speaking and mental arithmetic stress in 252 healthy young adults exposed
      to low, medium, and high levels of ELA and who were genotyped for the Val158Met
      polymorphism. RESULTS: Cortisol responses showed a G * E interaction (F(4,243) =
      2.78, p = .028); simple effects tests showed that Met/Met carriers had
      progressively smaller cortisol responses with greater levels of ELA. In
      comparison, Val/Val homozygotes had blunted responses that did not vary with ELA
      exposure. CONCLUSIONS: Met/Met homozygotes seem sensitive to stressful events in
      childhood and adolescence, leading to environmental programming of the stress
      axis. Glucocorticoid responsivity may represent a common pathway revealing
      targeted genetic vulnerabilities to the long-term effects of early life stress.
      The results suggest that further G * E studies of ELA are warranted in relation
      to health behaviors and health outcomes in adulthood.

PMID- 28452828
TI  - Telephone Encounters Predict Future High Financial Expenditures in Inflammatory
      Bowel Disease Patients: A 3-Year Prospective Observational Study.
AB  - BACKGROUND: Telephone activity is essential in management of complex chronic
      diseases including inflammatory bowel disease (IBD). Telephone encounters logged
      in the electronic medical record have recently been proposed as a surrogate
      marker of disease activity and impending health care utilization; however, the
      association between telephone calls and financial expenditures has not been
      evaluated. STUDY: We performed a 3-year prospective observational study of
      telephone encounters logged at a tertiary referral IBD center. We analyzed
      patient demographics, disease characteristics, comorbidities, clinical activity,
      and health care financial charges by telephone encounter frequency. RESULTS:
      Eight hundred one patients met inclusion criteria (52.3% female; mean age, 44.1
      y), accounted for 12,669 telephone encounters, and accrued $70,513,449 in charges
      over 3 years. High telephone encounter frequency was associated with female
      gender (P=0.003), anxiety/depression (P<0.001), and prior IBD surgery (P<0.001).
      High telephone encounter categories had significantly more hospitalizations
      (P<0.001), IBD surgery (P<0.001), worse quality of life (P<0.001), more
      corticosteroid (P<0.001), biological (P<0.001), and opiate prescriptions
      (P<0.001). High telephone encounter frequency patients amassed higher total
      available charges in each year (P<0.001) and over the 3 years (P<0.001).
      Telephone encounters in 2009 (P=0.02) and 2010 (P<0.001) were significantly
      associated with financial charges the following year after controlling for
      demographic, utilization, and medication covariates. CONCLUSIONS: Increased
      telephone encounters are associated with significantly higher health care
      utilization and financial expenditures. Increased call frequency is predictive of
      future health care spending. Telephone encounters are a useful tool to identify
      patients at risk of clinical deterioration and large financial expense.

PMID- 28452829
TI  - BTrackS Balance Test for Concussion Management is Resistant to Practice Effects.
AB  - OBJECTIVE: Recent guidelines advocate for ongoing balance testing in the
      assessment of management of concussion injuries. This study sought to determine
      whether the Balance Tracking System (BTrackS) provides stable balance results
      over repeated administration and, thus, is a reliable tool for concussion
      management. DESIGN: Repeated measures and test-retest reliability. SETTING:
      University Biomechanics Laboratory. PARTICIPANTS: Random sample of 20 healthy
      young adults. INTERVENTIONS: Force plate balance testing using BTrackS on days 1,
      3, 8, and 15. MAIN OUTCOME MEASURES: Practice-induced changes in the average
      center of pressure excursion over 4 repeated administrations of the BTrackS
      Balance Test (BBT). Test-retest reliability of center of pressure excursion from
      day 1 to day 15. RESULTS: No significant practice-induced balance differences
      were found across testing days (P > 0.4), and test-retest reliability of the BBT
      was excellent from day 1 to day 15 (R 0.92). CONCLUSIONS: These findings indicate
      that the BBT does not elicit a practice effect over repeat administrations.
      BTrackS provides excellent reliability and objectivity, which can increase
      clinician accuracy when monitoring sport-related concussions.

PMID- 28452830
TI  - First-Aid Treatment for Friction Blisters: "Walking Into the Right Direction?"
AB  - OBJECTIVE: Blisters are common foot injuries during and after prolonged walking.
      However, the best treatment remains unclear. The aim of the study was to compare
      the effect of 2 different friction blister treatment regimens, wide area fixation
      dressing versus adhesive tape. DESIGN: A prospective observational cohort study.
      SETTING: The 2015 Nijmegen Four Days Marches in the Netherlands. PARTICIPANTS: A
      total of 2907 participants (45 +/- 16 years, 52% men) were included and received
      4131 blister treatments. INTERVENTIONS: Blisters were treated with either a wide
      area fixation dressing or adhesive tape. MAIN OUTCOME MEASURES: Time of treatment
      application was our primary outcome. In addition, effectiveness and satisfaction
      were evaluated in a subgroup (n = 254). During a 1-month follow-up period,
      blister healing, infection and the need for additional medical treatment were
      assessed in the subgroup. RESULTS: Time of treatment application was lower (41.5
      minutes; SD = 21.6 minutes) in the wide area fixation dressing group compared
      with the adhesive tape group (43.4 minutes; SD = 25.5 minutes; P = 0.02).
      Furthermore, the wide area fixation dressing group demonstrated a significantly
      higher drop-out rate (11.7% vs 4.0%, P = 0.048), delayed blister healing (51.9%
      vs 35.3%, P = 0.02), and a trend toward lower satisfaction (P = 0.054) when
      compared with the adhesive tape group. CONCLUSIONS: Wide area fixation dressing
      decreased time of treatment application by 2 minutes (4.5%) when compared with
      adhesive tape. However, because of lower effectiveness and a trend toward lower
      satisfaction, we do not recommend the use of wide area fixation dressing over
      adhesive tape in routine first-aid treatment for friction blisters.

PMID- 28452831
TI  - Increased Level of Serum Hepcidin in Female Adolescent Athletes.
AB  - OBJECTIVE: To determine the serum hepcidin concentration and standard
      hematological parameters in a group of female adolescent athletes, compared with
      a group of nonathlete females. DESIGN: A case-control study. SETTING: A senior
      high school for athletes in Gothenburg, Sweden. PARTICIPANTS: All female athletes
      (70), at the school were offered to take part. Fifty-six athletes accepted. From
      a random sample of age-matched nonathletes, 71 students were recruited to the
      control group. MAIN OUTCOME MEASURES: Iron deficiency (ID) was determined by
      levels of serum iron, total iron-binding capacity, transferrin saturation (TS),
      and ferritin. Serum hepcidin was determined by a mass spectrometry method. All
      samples were taken at least 12 hours after training. RESULTS: The main result was
      the finding of a significantly elevated serum hepcidin level in the athlete
      group, 4.7 nmol/L compared with 3.3 nmol/L (P < 0.001) in the nonathlete group.
      In the athlete group, the serum iron concentration was significantly lower, 14.0
      MUmol/L compared with 17.6 MUmol/L (P = 0.003) in the nonathlete group. No
      difference was found regarding TS, total iron binding capacity, and ferritin.
      There was no difference in the occurrence of ID or iron deficiency anaemia (IDA).
      CONCLUSIONS: These findings show an increase in serum hepcidin in a large group
      of female athletes. The elevated hepcidin levels may affect the iron balance of
      the athletes, adding to the traditional explanation of dietary intake/iron loss
      balance.

PMID- 28452832
TI  - Shoulder Dynamic Control Ratio and Rotation Range of Motion in Female Junior
      Elite Handball Players and Controls.
AB  - OBJECTIVE: To compare glenohumeral range of motion and shoulder rotator muscle
      strength in healthy female junior elite handball players and controls. DESIGN:
      Cross-sectional case-control study. SETTING: Sports medical center. PARTICIPANTS:
      Forty elite female handball players and 30 controls active in nonoverhead sports
      participated in this study. MAIN OUTCOME MEASURES: Passive external rotator (ER),
      internal rotator (IR), and total range of motion (TROM) of the dominant and
      nondominant arm were examined with a goniometer. An isokinetic dynamometer was
      used to evaluate concentric and eccentric rotator muscle strength at 60 and 120
      degrees/s with dynamic control ratio (DCR = ERecc:IRcon) as the main outcome
      parameter. RESULTS: Except for the ER range of motion in the nondominant arm, no
      significant differences were found between groups for IR, ER of the dominant arm,
      and the TROM. Within the handball group, the side-to-side difference for IR of
      the dominant arm was -1.4 degrees. The ER and the TROM of the dominant arm were
      significantly larger, 6.3 and 4.9 degrees, respectively. For both groups, the DCR
      values were above 1 and no significant differences were found between the
      dominant and nondominant arm. The DCR values in the handball group were
      significantly lower than in the control group. CONCLUSIONS: Based on the adopted
      definitions for muscle imbalance, glenohumeral internal range of motion deficit
      and TROM deficit our elite female handball players seem not at risk for shoulder
      injuries. Prospective studies are needed to support the belief that a DCR below 1
      places the shoulder at risk for injury.

PMID- 28452833
TI  - Neoadjuvant Therapy Combined With Oncoplastic Reduction for High-Stage Breast
      Cancer Patients.
AB  - OBJECTIVE: Oncoplastic surgery has been shown to be a good alternative to breast
      conservation surgery (BCS) alone for patients with breast cancer. Its role in
      patients with advanced disease is unclear. In this study, we evaluate the safety
      of oncoplastic BCS (OBCS) in patients who received neoadjuvant therapy (NT) for
      high stage breast cancer. METHODS: The oncologic outcomes of consecutive patients
      classified as high stage (>T2 or at least N1) who received NT followed by BCS at
      EUH by a single breast surgeon (T.M.S.) from September 2004 until June 2015 were
      compared with those who received BCS combined with an oncoplastic reduction.
      Patients were surveyed using the BREAST-Q to determine their satisfaction after
      surgery. RESULTS: A total of 87 patients were included in this series. The mean
      initial tumor size (4.37 vs 2.56 cm), the weight of the surgical specimen, and
      the post-NT tumor size were all larger in the OBCS group as compared with BCS
      alone (1.54 vs 1.29 cm). The mean follow-up was 44 months. The average percent
      reduction in tumor size in response to NT was slightly greater in the OBCS group
      (61 vs 52%). Oncologic outcomes were similar for OBCS reduction and BCS groups,
      respectively: positive margin rate, reexcision rate, completion mastectomy rate,
      local recurrence rate, and 5-year DSS. Patient satisfaction was similar between
      the 2 groups. CONCLUSIONS: The oncoplastic approach in high stage patients
      treated with neoadjuvant systemic Powered by Editorial Manager and ProduXion
      Manager from Aries Systems Corporation therapy appears to be as safe and
      effective when compared to BCS alone. Oncoplastic BCS paired with NT broadens the
      indication for BCS for patients with larger tumor size.

PMID- 28452835
TI  - Vitamin D Status, Cardiometabolic, Liver, and Mental Health Status in Obese Youth
      Attending a Pediatric Weight Management Center.
AB  - BACKGROUND: Vitamin D (VitD) deficiency and obesity are reaching epidemic
      proportions in North America, particularly in those with comorbid conditions such
      as diabetes or liver disease. The study objective was to determine the prevalence
      of suboptimal vitD status and interrelationships with anthropometric,
      cardiometabolic, liver, mental health, and lifestyle (sleep/screen time)
      parameters in an ambulatory population of children with obesity. METHODS:
      Children (2-18 years) attending a pediatric weight management clinic (n = 217)
      were retrospectively reviewed. Variables studied included anthropometric (weight,
      height, body mass index, waist circumference), vitD (serum 25-hydroxyvitamin D),
      cardiometabolic (systolic blood pressure, diastolic blood pressure, glucose,
      insulin, homeostasis model assessment for insulin resistance, triglyceride, high
      density lipoprotein, low-density lipoprotein, total cholesterol), liver enzymes
      (alanine aminotransferase, gamma-glutamyl transferase), and mental health
      (number, diagnosis) parameters. RESULTS: Suboptimal vitD status (25
      hydroxyvitamin D <75 nmol/L was present in 76% of children with obesity (12.0 +/-
      2.9 years). Blood pressure categorized as prehypertension, stage I hypertension,
      and stage II hypertension was present in 14%, 25%, and 7% of children,
      respectively. Mental health diagnoses including anxiety, attention-deficit
      hyperactivity disorder, mood disorders, and learning disabilities/developmental
      delays occurred in 18%, 17%, 10%, and 15%, of children, respectively. Waist
      circumferences >100 cm were associated with lower vitD levels (58 +/- 18 vs 65 +/
      17 nmol/L; P = 0.01). VitD status >=50 nmol/L was associated with lower insulin
      (15.8 [11.7-23.1] mU/L vs 21.1 [14.3-34.2] mU/L; P < 0.01) and homeostasis model
      assessment for insulin resistance (3.5 [2.5-4.9] vs 4.8 [3.1-6.9]; P < 0.01)
      values and systolic blood pressure percentiles (73.0 +/- 25.8 vs 80.6 +/- 17.0; P
      = 0.04). CONCLUSIONS: Children with obesity had a high prevalence of vitD
      deficiency, particularly those at risk for hypertension, reduced insulin
      sensitivity, and central obesity.

PMID- 28452837
TI  - Factors Related to Self-rated Health in Older Adults: A Clinical Approach Using
      the International Classification of Functioning, Disability, and Health (ICF)
      Model.
AB  - BACKGROUND AND PURPOSE: A growing population of older adults will require health
      care professionals to become increasingly knowledgeable in geriatric care.
      Patient ratings, functional measures, and emphasis on health and wellness should
      be part of geriatric physical therapy practice. The purpose of the current study
      was to examine relationships between self-rated health (SRH) and movement-related
      variables in older adults using the International Classification of Functioning,
      Disability, and Health (ICF) as a research framework. Associations between body
      mass index (BMI), gait, and balance confidence were also explored. METHODS:
      Thirty older adults (mean age = 74.1 years; 18 women and 12 men) participated in
      the study and completed the following questionnaires: SRH, Short Activities
      specific Balance Confidence scale, Keele Assessment of Participation, and the
      Neighborhood Environment Walkability Scale-Abbreviated. Spatiotemporal gait
      parameters, BMI, and isokinetic knee extensor strength were also assessed.
      RESULTS: Bivariate results indicated significant associations between SRH and
      double-support time during gait (rs = -0.6, P < .001), gait speed (rs = 0.4, P =
      .05), step length (rs = 0.4, P = .05), BMI (rs = -0.4, P = .015), and hilliness
      of neighborhood (rs = -0.4, P = .015). Individual regression models, controlling
      for education and age, demonstrated that double-support time was the strongest
      predictor of SRH (R = 0.50, P = .001). Comparisons of the low versus high BMI
      groups indicated more favorable balance confidence and gait characteristics for
      the low BMI group, particularly in double support (t = -3.8, P = .001).
      CONCLUSIONS: SRH should be considered as a quick, patient-focused assessment of
      health in older adults. Measures of double-support time and BMI may provide
      clinicians with useful information about their geriatric patients' overall health
      and function.

PMID- 28452838
TI  - Later Development of Posterior Staphyloma in Choroidal Osteoma With Choroidal
      Neovascularization.

PMID- 28452840
TI  - Silicone Oil Removal From the Anterior Chamber Using Dispersive Viscoelastic.

PMID- 28452839
TI  - HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK
      ADAPTATION.
AB  - PURPOSE: To determine the association between dark adaption (DA) and different
      health conditions linked with age-related macular degeneration (AMD). METHODS:
      Cross-sectional study, including patients with AMD and a control group. Age
      related macular degeneration was graded according to the Age-Related Eye Disease
      Study (AREDS) classification. We obtained data on medical history, medications,
      and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes)
      of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced
      AMD was selected. Multivariate linear and logistic regressions were performed,
      accounting for age and AMD stage. RESULTS: Seventy-eight subjects (75.6% AMD;
      24.4% controls) were included. Multivariate assessments revealed that body mass
      index (BMI; beta = 0.30, P = 0.045), taking AREDS vitamins (beta = 5.51, P <
      0.001), and family history of AMD (beta = 2.68, P = 0.039) were significantly
      associated with worse rod intercept times. Abnormal DA (rod intercept time >= 6.5
      minutes) was significantly associated with family history of AMD (beta = 1.84, P
      = 0.006), taking AREDS supplements (beta = 1.67, P = 0.021) and alcohol intake
      (beta = 0.07, P = 0.017). CONCLUSION: Besides age and AMD stage, a higher body
      mass index, higher alcohol intake, and a family history of AMD seem to impair DA.
      In this cohort, the use of AREDS vitamins was also statistically linked with
      impaired DA, most likely because of an increased severity of disease in subjects
      taking them.

PMID- 28452841
TI  - Are We Over-Treating Insect Bite Related Periorbital Cellulitis in Children? The
      Experience of a Large, Tertiary Care Pediatric Hospital.
AB  - INTRODUCTION: Preseptal (periorbital) and orbital cellulitis are potentially
      catastrophic infections near the eye. Preseptal cellulitis is far more common,
      and although classically reported to be associated with dacrocystitis,
      sinusitis/upper respiratory infection, trauma/surgery, or infection from
      contiguous areas, it can also be associated with insect bites. The objective of
      this study was to determine the prevalence of insect bite-associated preseptal
      cellulitis and to compare clinical findings and outcomes of these patients with
      those having other causes for the condition. METHODS: Retrospective chart review
      of children with a final discharge diagnosis of periorbital cellulitis from
      January 2009 to December 2014 at a tertiary care children' hospital. RESULTS: 213
      children were diagnosed with preseptal cellulitis during the 5-year study period,
      of whom 60 (28%) were associated with insect bites. Patients in the noninsect
      bite group more commonly had fever at presentation (P < 0.001), with increased
      white blood cell and C reactive protein values (both P < 0.001). No patient with
      insect bite-associated preseptal cellulitis presented with fever, and none
      underwent radiographic testing or computerized tomography; their mean age was
      also lower (P < 0.001) and length of stay was significantly shorter. CONCLUSIONS:
      This study suggests that children with preseptal cellulitis associated with
      insect bites could be candidates for oral antibiotic therapy with outpatient
      follow-up by.

PMID- 28452842
TI  - Adaptive Servo Ventilation in Heart Failure.

PMID- 28452843
TI  - The Impact of Proton Pump Inhibition on Dabigatran Levels in Patients With Atrial
      Fibrillation.
AB  - BACKGROUND: Proton pump inhibition (PPI) administrated together with dabigatran
      reduces the risk of gastrointestinal hemorrhage. However, there is a discussion
      regarding possible PPI-dabigatran interaction that may reduce the efficacy of
      this therapy. STUDY QUESTION: To determine the impact of concomitant PPI on
      dabigatran plasma levels in patients with nonvalvular atrial fibrillation (NV
      AF). STUDY DESIGN: A pilot prospective study in patients with NV-AF on dabigatran
      therapy was performed; 31 patients were enrolled. PPI with either omeprazole or
      pantoprazole was administrated in 19 patients. MEASURES AND OUTCOMES: Blood
      samples were taken for the assessment of the dabigatran trough and peak levels.
      Dabigatran concentration was measured with the Hemoclot Thrombin Inhibitor Assay.
      RESULTS: There were significant differences in dabigatran trough level comparing
      patients treated with PPI and patients without PPI (58.86 +/- 36.76 ng/mL vs.
      110.72 +/- 88.47 ng/mL, P < 0.05). Similarly, there were significant differences
      in dabigatran peak level between compared groups (88.0 +/- 20.5 ng/mL vs. 174.4
      +/- 139.64 ng/mL, P < 0.05). CONCLUSIONS: This pilot study demonstrated the
      interaction between PPI and dabigatran levels in patients with NV-AF.

PMID- 28452844
TI  - Life Threatening Angioedema Due to Valsartan/Sacubitril With Previously Well
      Tolerated ACE Inhibitor.

PMID- 28452845
TI  - Dronabinol-Induced Acute Altered Mental Status in an Elderly Patient.

PMID- 28452846
TI  - Abiraterone-Associated Fulminant Liver Failure.

PMID- 28452847
TI  - Ranolazine-Associated Myoclonus.

PMID- 28452848
TI  - Euglycemic Ketoacidosis With Sodium-Glucose Cotransporter-2 Inhibitor.

PMID- 28452849
TI  - Ipilimumab-induced Guillain-Barre Syndrome Presenting as Dysautonomia: An Unusual
      Presentation of a Rare Complication of Immunotherapy.
AB  - Immune-related adverse events are common and well-documented in patients treated
      with ipilimumab, a cytotoxic T-lymphocyte antigen-4 monoclonal antibody approved
      for the treatment of metastatic and stage III melanoma. Neurological
      complications are rare, but widely variable and potentially devastating. Here, we
      discuss a case of a patient who was treated with a single dose of ipilimumab for
      resected stage III melanoma. She subsequently developed pandysautonomia that
      manifested as a tonically dilated pupil, gastrointestinal dysmotility, urinary
      retention, and profound orthostatic hypotension. Guillain-Barre syndrome was
      diagnosed on electromyography. She was treated with intravenous immunoglobulin,
      droxidopa, and supportive care, with prolonged but eventual recovery. Given the
      broadening use of ipilimumab in the treatment of advanced and metastatic
      melanoma, awareness and recognition of its profound immune-mediated adverse
      effects are essential.

PMID- 28452850
TI  - Sunitinib Induces NK-kappaB-dependent NKG2D Ligand Expression in Nasopharyngeal
      Carcinoma and Hepatoma Cells.
AB  - Multitargeted tyrosine kinase inhibitors (MTKIs) have been shown to combine with
      natural killer (NK) cell adoptive transfer for the treatment in various cancers.
      MTKIs sensitize cancer cells to NK cell therapy through upregulation of nature
      killer group 2 member D ligands (NKG2DLs) on tumor cells. However, the molecular
      mechanism of MTKIs-mediated upregulation of NKG2DLs is still unknown. In this
      study, we confirmed sunitinib induced downregulation of its targets, such as
      vascular endothelial growth factor, platelet-derived growth factor, and c-kit in
      multiple-drug-resistant nasopharyngeal carcinoma cell line CNE2/DDP and hepatoma
      cell line HepG2. Then, we further showed sunitinib induced cell proliferation
      inhibition, apoptosis, and DNA damage in CNE2/DDP and HepG2 cells. Coculture
      experiments showed that sunitinib-treated CNE2/DDP and HepG2 cells were able to
      increase the activation and cytotoxicity of NK cells. Quantitative polymerase
      chain reaction results showed that sunitinib upregulated NKG2DLs, apoptotic
      genes, DNA damage repair genes, and nuclear factor (NF)-kappabeta family genes.
      Silencing of NF-kappabeta1, NF-kappabeta2, or RelB (NF-kappabeta pathway)
      inhibited sunitinib-induced upregulation of NKG2DLs. Taken together, we concluded
      that sunitinib upregulated NKG2DLs through NF-kappabeta signaling noncanonical
      pathway which might mediate higher cytotoxic sensitivity of CNE2/DDP and HepG2
      cells to NK cells.

PMID- 28452851
TI  - The 14th Hoyt Lecture Ischemic Optic Neuropathy: The Evolving Profile, 1966-2015:
      Comment.

PMID- 28452852
TI  - The 14th Hoyt Lecture: Ischemic Optic Neuropathy: The Evolving Profile, 1966
      2015: Response.

PMID- 28452853
TI  - Diagnosing and managing mitral regurgitation.
AB  - Mitral regurgitation is the most prevalent valvular disorder in the United
      States. Patient presentation varies from asymptomatic to symptoms of severe heart
      failure. Primary care providers often are the first to detect mitral
      regurgitation as a result of careful auscultation. Medical management focuses on
      reducing cardiac workload, combating cardiac remodeling, and treating left
      ventricular failure. Surgical management is reserved for severe cases.

PMID- 28452854
TI  - Caring for a patient with first-trimester bleeding.
AB  - This article provides a review of the general features, clinical assessment,
      diagnosis, and treatment of bleeding in the first trimester of pregnancy.

PMID- 28452855
TI  - Novel Mutations Resulting in a Moderate to Severe Phenotypic Manifestation of
      Hemophilia A in a Female.
AB  - Hemophilia A is an X-linked, recessive disorder resulting from mutations in the
      f8 gene. Here we report the rare case of a female compound heterozygote with mild
      factor VIII deficiency (fVIII:C 9%) and moderate phenotype. On investigation she
      was confirmed to have normal Von Willebrand factor studies with a 46XY genotype.
      Further genetic testing revealed 3 mutations in the f8 gene: 1 novel missense
      mutation (c.6142T>G), 1 novel in-frame deletion (c.1281_1292del), and another
      missense mutation of unclear significance (c.3780C>G). Both parents had normal
      coagulation profiles; however, the 2 novel mutations were present in the
      patient's mother and the known missense mutation was present in her father. This
      unusual case demonstrates the utility in genetic analysis for f8 gene mutational
      analysis and suggests a compound effect of the 3 identified mutations as a cause
      for factor deficiency.

PMID- 28452857
TI  - A Case of Hemophagocytic Lymphohistiocytosis and Kawasaki Disease: Concurrent or
      Overlapping Diagnoses?
AB  - Hemophagocytic lymphohistiocytosis (HLH) is not always suspected at the time of
      presentation. It is often mistaken for other diagnoses; complicated by the fact
      that it is often associated with an inciting event that has significant overlap.
      Kawasaki disease, along with other disorders, such as Ebstein Barr Virus
      infection, are conditions that may lead HLH. Our patient had a presentation that
      was consistent with Kawasaki disease on initial presentation, however
      subsequently met the diagnostic criteria of HLH. It provided an interesting
      discussion about diagnoses with clinical criteria and how the overlap can
      sometimes delay or complicate initial diagnosis.

PMID- 28452856
TI  - Administration of Dexrazoxane Improves Cardiac Indices in Children and Young
      Adults With Acute Myeloid Leukemia (AML) While Maintaining Survival Outcomes.
AB  - Anthracycline-induced cardiotoxicity remains a significant contributor to late
      morbidity/mortality in children and young adults with acute myeloid leukemia
      (AML). The cardioprotectant dexrazoxane can be used as prophylaxis to diminish
      risk for cardiomyopathy but whether it affects risk of relapse in pediatric AML
      is unclear. Our institution adopted the use of dexrazoxane before anthracyclines
      administration for all oncology patients in 2011. We compared patients with AML
      (ages, 0 to 21 y) who received or did not receive dexrazoxane during the years
      2008 to 2013. In total, 44 patients with AML (ages, 4.5 mo to 21.7 y) were
      included. We identified no statistical difference in 2-year event rate (62% vs.
      50%, P=0.41) or 2-year overall survival (69% vs. 69%, P=0.53) between patients
      receiving (n=28) or not receiving (n=16) dexrazoxane. Ejection fraction
      (P=0.0262) and shortening fraction (P=0.0381) trended significantly higher in
      patients that received dexrazoxane compared with those that did not receive
      dexrazoxane. Utilization of the cardioprotectant dexrazoxane before anthracycline
      chemotherapy in pediatric patients with AML demonstrated no significant
      difference in either event rate or overall survival relative to institutional
      controls and seems to improve cardiac function indices. Further studies in this
      patient population are needed to confirm these findings.

PMID- 28452858
TI  - Primary Bone Anaplastic Large Cell Lymphoma Masquerading as Ewing Sarcoma:
      Diagnosis by Anchored Multiplex PCR.
AB  - A 3-year-old boy presented with pathologic fracture of the left proximal femur.
      Magnetic resonance imaging revealed an aggressive expansile bony mass associated
      with cortical destruction and surrounding myositis. Computed tomography-guided
      biopsy revealed a monomorphic small round blue cell tumor by histology. CD99
      immunoreactivity and low-level EWSR1 gene translocation by break-apart
      fluorescent in situ hybridization initially favored a diagnosis of Ewing sarcoma
      and chemotherapy commenced. Subsequent molecular evaluation by an anchored
      multiplex polymerase chain reaction-based assay (Archer FusionPlex Sarcoma Panel)
      revealed a nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) gene fusion. The
      diagnosis was then amended to primary bone ALK-positive anaplastic large cell
      lymphoma and the chemotherapy regimen was modified accordingly. This report
      illustrates the value of this molecular assay in establishing the correct
      diagnosis of a very rare malignancy masquerading as another tumor type.

PMID- 28452859
TI  - TERT-mediated and ATRX-mediated Telomere Maintenance and Neuroblastoma.
AB  - Neuroblastomas (NB) are one of the most common extracranial solid tumors in
      children, and they frequently display high heterogeneity in the disease course.
      With ongoing research, more information regarding the genetic etiology and
      molecular mechanisms underlying these contrasting phenotypes is being uncovered.
      The proto-oncogene MYCN is amplified in approximately 20% of NB cases and is
      considered a indicator of poor prognosis and an indicator of high-risk NB. The
      poor prognosis of high risk NB is incompletely explained by MYCN amplification.
      Recently, massive parallel sequencing studies reported several relatively common
      gene alterations, such as ATRX mutation and TERT rearrangement that are involved
      in telomere maintenance through telomerase activity and alternative lengthening
      of telomeres. Thus, these are important for understanding the etiology and
      molecular pathogenesis of NB, and hence, for identifying diagnostic and treatment
      markers. Development of telomerase inhibitors and identification of alternative
      lengthening of telomeres related targets will contribute to the individualized
      treatment for high-risk NB. In this mini-review, we will discuss the research
      progress of TERT-mediated and ATRX-mediated telomere maintenance and NB,
      especially high-risk tumors.

PMID- 28452860
TI  - Osteonecrosis of the Shoulders in Pediatric Patients Treated for Leukemia or
      Lymphoma: Single-Institutional Experience.
AB  - BACKGROUND: Osteonecrosis of the hips and knees is an often debilitating adverse
      event in children treated with glucocorticoids for leukemia and lymphoma but the
      impact of shoulder involvement has been understudied. Thus, we investigated the
      severity and functional impairment of shoulder osteonecrosis in a well
      characterized population of pediatric patients treated for acute lymphoblastic
      leukemia or lymphoma. METHODS: We retrospectively reviewed orthopaedic clinic and
      physical therapy evaluations to determine range of motion (ROM), pain, and impact
      of magnetic resonance-defined osteonecrosis (ON) on activities of daily living.
      Adverse events were classified according to the National Cancer Institute's
      Common Terminology Criteria for Adverse Events version 4.03. RESULTS: We
      identified 35 patients (22 female), median age at cancer diagnosis 14.2 (range,
      4.3 to 19) years; median age at ON diagnosis 16.7 (range, 5.5 to 28) years.
      Median time to last follow-up from diagnosis of primary malignancy was 6.4
      (range, 0 to 12.7) years and from diagnosis of ON was 4.0 (range, 0 to 8.9)
      years. Twenty-two patients had magnetic resonance evidence of ON; 43 shoulders
      involved at least 30% of the articular surface of the capital humeral
      epiphyses.Common Terminology Criteria for Adverse Events mean scores for initial
      assessments of 55 shoulders (29 patients) showed moderate negative impact of ON
      on activity of daily living (1.94), decreased ROM limiting athletic activity
      (0.98), and mild to moderate levels of pain (1.38). Analysis of this group's most
      recent assessment showed improvement in pain and ON over time, with an average
      pain grade of 0.58 indicating no pain to mild pain, and 1.37 for ON grade,
      indicating asymptomatic to mildly symptomatic impact on activities of daily
      living. We also found minimal worsening average ROM grades (1.11). CONCLUSIONS:
      Shoulder ON is an underappreciated adverse late effect of therapy in children
      treated for leukemia/lymphoma which can limit quality of life and functionality.
      In most cases, pain and disability can be improved with treatment. LEVEL OF
      EVIDENCE: Level IV-case series.

PMID- 28452861
TI  - Inadequate Gestational Weight Gain, the Hidden Link Between Maternal IBD and
      Adverse Pregnancy Outcomes: Results from the Norwegian Mother and Child Cohort
      Study.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) are in general prone
      to weight loss. We explored the risk of inadequate gestational weight gain (GWG),
      and the impact of GWG on adverse pregnancy outcomes, among mothers with IBD in
      the Norwegian Mother and Child Cohort Study (MoBa). METHODS: The MoBa with 95,200
      mothers enrolled from 1999 to 2008, comprised 217 mothers with ulcerative colitis
      and 166 with Crohn's disease. Demographics were ascertained through a basic
      questionnaire before the first ultrasound visit and an IBD history and disease
      activity during pregnancy through a questionnaire mailed out in 2013. Inadequate
      GWG was based on the US Institute of Medicine recommendations. The associations
      between IBD and inadequate GWG or adverse pregnancy outcomes were explored,
      adjusted for diabetes, hypertension, smoking, maternal age, education, and
      disease activity. RESULTS: Mothers with Crohn's disease (34.3%) and ulcerative
      colitis (26.7%) were more frequently exposed to inadequate GWG compared with non
      IBD mothers (19.4%) (adjusted odds ratio [aOR] = 2.02, 95% confidence interval
      [CI], 1.42-2.86 and aOR = 1.46, 95% CI, 1.04-2.05, respectively). Mothers with
      IBD with inadequate GWG (exposed) had a 2-fold risk of small for gestational age
      infants compared with exposed non-IBD mothers (aOR = 1.93, 95% CI, 1.13-3.29).
      Exposed mothers with Crohn's disease and ulcerative colitis had a several-fold
      increased risk of small for gestational age compared with nonexposed IBD mothers
      (aOR = 4.5, 95% CI, 1.3-16.2, aOR = 5.5, 95% CI, 1.6-18.5). Disease activity was
      associated with reduced GWG (<13 kg compared with >17.5 kg) (aOR = 3.34, 95% CI,
      1.33-8.38). CONCLUSIONS: Inadequate GWG should be considered as a risk factor for
      adverse pregnancy outcomes or as a marker of disease activity.

PMID- 28452862
TI  - Anti-TNF Treatment for Extraintestinal Manifestations of Inflammatory Bowel
      Disease in the Swiss IBD Cohort Study.
AB  - BACKGROUND: Extraintestinal manifestations (EIMs) in patients with inflammatory
      bowel disease (IBD) are frequently observed. Little is known about the efficacy
      of anti-tumor necrosis factor (TNF) in EIM management. We assessed the effect of
      3 anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) on EIM
      evolution. METHODS: Data on 1249 patients from the Swiss IBD Cohort Study
      (SIBDCS) were analyzed. All EIMs were diagnosed by relevant specialists. Response
      was classified into improvement, stable disease, and clinical worsening based on
      the physician's interpretation. RESULTS: Of the 366 patients with at least 1 EIM,
      213 (58.2%) were ever treated with an anti-TNF. A total of 299 treatments were
      started for 355 EIMs. Patients with EIM were significantly more often treated
      with anti-TNF compared with those without EIM (58.2% versus 21.0%, P < 0.001).
      Infliximab was the most frequently used drug (63.2%). In more than 71.8%, a
      clinical response of the underlying EIM to anti-TNF therapy was observed. In 92
      patients (43.2%), anti-TNF treatments were started for the purpose of treating
      EIM rather than IBD. Response rates to anti-TNF were generally good and best for
      psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis. In 11
      patients, 14 EIM occurred under anti-TNF treatment. CONCLUSIONS: Anti-TNF was
      frequently used among patients with EIM. In more than 40%, anti-TNF treatments
      are started to treat EIM rather than IBD. Given the good response rates, anti-TNF
      seems to be a valuable option in the treatment of EIM, whereas appearance of EIM
      under anti-TNF does not seem to be a source of considerable concern.

PMID- 28452863
TI  - Efficacy and Factors Associated with Treatment Response of Intravenous
      Immunoglobulin in Inpatients with Refractory Inflammatory Bowel Diseases.
AB  - BACKGROUND: The administration of intravenous immunoglobulin (IVIG) has
      demonstrated promise in the treatment of medically refractory inflammatory bowel
      diseases (IBD). We aimed to identify factors associated with IVIG failures in the
      treatment of refractory IBD. METHODS: Our historical cohort included patients
      with refractory IBD admitted to our inpatient service with an exacerbation and
      treated with at least 1 dose of IVIG (0.4 g/kg). Detailed clinical variables were
      recorded for subjects. Examined outcomes included changes in disease-specific
      severity indices, the duration of surgery-free survival after IVIG, infusion
      reactions, subsequent IBD-related emergency department visits, hospital
      readmissions, and mortality. RESULTS: Fifty-four subjects with refractory IBD
      (61% female, age 42 +/- 16 yrs, 23 with Crohn's disease, 15 with ulcerative
      colitis, 16 with pouchitis) met the inclusion criteria. All disease severity
      scores were significantly improved after IVIG administration (Harvey-Bradshaw
      index P = 0.007, partial Mayo score P = 0.002, modified Pouchitis Disease
      Activity Index P = 0.008). Twenty-seven patients (50%) underwent surgery, with a
      mean surgery-free survival of 28.7 +/- 3.7 months. In univariable analysis,
      patients with Clostridium difficile infection (CDI) had a 3-fold increased risk
      of bowel resection surgery after IVIG compared with those without (hazard ratio =
      2.9, 95% confidence interval, 1.2-7.4; P = 0.023), and in subsequent
      multivariable analysis, CDI remained significant (hazard ratio = 3.0, 95%
      confidence interval, 1.2-7.6; P = 0.024). CDI was also associated with increased
      risk of hospital readmission (hazard ratio = 2.5, 95% confidence interval, 1.05
      5.9; P = 0.038). CONCLUSIONS: Our study demonstrates that IVIG is beneficial in
      patients with medically refractory IBD, and that concomitant CDI is a risk factor
      for the treatment failure of IVIG for refractory disease.

PMID- 28452865
TI  - Are All Heat Loads Created Equal?
AB  - PURPOSE: We evaluated physiological responses during exercise at a fixed
      evaporative requirement for heat balance (Ereq) but varying combinations of
      metabolic and environmental heat load. METHODS: Nine healthy, physically active
      males (age: 46 +/- 8 yr) performed four experimental sessions consisting of 75
      min of semirecumbent cycling at various ambient temperatures. Whole-body dry heat
      loss (direct calorimetry) was monitored continuously as was heat production
      (indirect calorimetry), which was adjusted to achieve an Ereq of 400 W. The
      resultant metabolic heat productions and ambient temperatures for the sessions
      were as follows: (i) 440 W and 30 degrees C (440 [30]), (ii) 388 W and 35 degrees
      C (388 [35]), (iii) 317 W and 40 degrees C (317 [40]), and (iv) 258 W and 45
      degrees C (258 [45]). Whole-body evaporative heat loss was determined via direct
      calorimetry. Esophageal (Tes) and mean skin (Tsk) temperatures as well as HR were
      monitored continuously. Mean body temperature (Tb) was calculated from Tes and
      Tsk. Physiological strain index (PSI) was determined from Tes and HR. RESULTS:
      End-exercise evaporative heat loss and Tb were similar between conditions (both P
      >= 0.48). Tes was greater in 440 [30] (37.67 degrees C +/- 0.04 degrees C) and
      388 [35] (37.58 degrees C +/- 0.07 degrees C) relative to both 317 [40] (37.35
      degrees C +/- 0.06 degrees C) and 258 [45] (37.20 degrees C +/- 0.07 degrees C;
      all P <= 0.05). Further, Tsk was different between each condition (440 [30],
      33.85 degrees C +/- 0.16 degrees C; 388 [35], 34.53 degrees C +/- 0.08 degrees C;
      317 [40], 35.67 degrees C +/- 0.07 degrees C; and 258 [45], 36.54 degrees C +/-
      0.08 degrees C; all P < 0.01). In 440 [30], HR was elevated by about 13 and 18
      bpm relative to 317 [40] and 258 [45], respectively (both P < 0.01). Finally, PSI
      was greater in both 440 [30] and 388 [35] compared with 317 [40] and 258 [45]
      (all P <= 0.04). CONCLUSIONS: Exercise at a fixed Ereq resulted in similar
      evaporative heat loss and Tb. However, the Tes, Tsk, HR, and PSI responses varied
      depending on the relative contribution of metabolic and environmental heat load.

PMID- 28452864
TI  - Azathioprine with Allopurinol: Lower Deoxythioguanosine in DNA and Transcriptome
      Changes Indicate Mechanistic Differences to Azathioprine Alone.
AB  - BACKGROUND: Use of azathioprine (AZA) for inflammatory bowel disease is limited
      by side effects or poor efficacy. Combining low-dose azathioprine with
      allopurinol (LDAA) bypasses side effects, improves efficacy, and may be
      appropriate as first-line therapy. We test the hypothesis that standard-dose
      azathioprine (AZA) and LDAA treatments work by similar mechanisms, using
      incorporation of the metabolite deoxythioguanosine into patient DNA, white-blood
      cell counts, and transcriptome analysis as biological markers of drug effect.
      METHODS: DNA was extracted from peripheral whole-blood from patients with IBD
      treated with AZA or LDAA, and analyzed for DNA-incorporated deoxythioguanosine.
      Measurement of red-blood cell thiopurine metabolites was part of usual clinical
      practice, and pre- and on-treatment (12 wk) blood samples were used for
      transcriptome analysis. RESULTS: There were no differences in reduction of white
      cell counts between the 2 treatment groups, but patients on LDAA had lower DNA
      incorporated deoxythioguanosine than those on AZA; for both groups, incorporated
      deoxythioguanosine was lower in patients on thiopurines for 24 weeks or more
      (maintenance of remission) compared to patients treated for less than 24 weeks
      (achievement of remission). Patients on LDAA had higher levels of red-blood cell
      thioguanine nucleotides than those on AZA, but there was no correlation between
      these or their methylated metabolites, and incorporated deoxythioguanosine.
      Transcriptome analysis suggested down-regulation of immune responses consistent
      with effective immunosuppression in patients receiving LDAA, with evidence for
      different mechanisms of action between the 2 therapies. CONCLUSIONS: LDAA is
      biologically effective despite lower deoxythioguanosine incorporation into DNA,
      and has different mechanisms of action compared to standard-dose azathioprine.

PMID- 28452866
TI  - Effects of Dopamine and Norepinephrine on Exercise-induced Oculomotor Fatigue.
AB  - INTRODUCTION: Fatigue-induced impairments in the control of eye movements are
      detectable via reduced eye movement velocity after a bout of prolonged, strenuous
      exercise. Slower eye movements caused by neural fatigue within the oculomotor
      system can be prevented by caffeine, and the upregulation of central
      catecholamines may be responsible for this effect. This study explored the
      individual contribution of dopamine and norepinephrine to fatigue-related
      impairments in oculomotor control. METHODS: The influence of a dopamine reuptake
      inhibitor (methylphenidate) and a norepinephrine reuptake inhibitor (reboxetine)
      was assessed in 12 cyclists performing 180 min of stationary cycling within a
      placebo-controlled crossover design. Eye movement kinematics (saccades, smooth
      pursuit, and optokinetic nystagmus) were measured using infrared oculography.
      Visual attention was assessed with overt and covert spatial attention tasks.
      RESULTS: Exercise-induced fatigue was associated with a 6% +/- 8% reduction in
      the peak velocity of visually guided, reflexive prosaccades. Importantly, both
      dopamine reuptake inhibition and norepinephrine reuptake inhibition prevented
      fatigue-related decrements in the peak velocity of prosaccades. Pursuit eye
      movements, optokinetic nystagmus, and visual attention tasks were unaffected by
      exercise or drug treatments. CONCLUSION: Overall, our findings suggest that
      alterations in norepinephrinergic and dopaminergic neurotransmission are linked
      with the development of fatigue within circuits that control eye movements.
      Psychiatric medications that target central catecholamines can exert a protective
      effect on eye movements after prolonged exercise.

PMID- 28452867
TI  - Vulvar Bowenoid Papulosis: Histologically High-Grade Squamous Intraepithelial
      Lesion Known to Spontaneously Regress.

PMID- 28452868
TI  - The Case for Funding Our National Drug Safety Surveillance System.

PMID- 28452869
TI  - Unusual source of gastrointestinal hemorrhage after inferior vena cava ligation.

PMID- 28452870
TI  - Every minute counts: Time to delivery of initial massive transfusion cooler and
      its impact on mortality.
AB  - BACKGROUND: American College of Surgeons Trauma Quality Improvement Best
      Practices recommends initial massive transfusion (MT) cooler delivery within 15
      minutes of protocol activation, with a goal of 10 minutes. The current study
      sought to examine the impact of timing of first cooler delivery on patient
      outcomes. METHODS: Patients predicted to receive MT at 12 Level I trauma centers
      were randomized to two separate transfusion ratios as described in the PROPPR
      trial. Assessment of Blood Consumption score or clinician gestalt prediction of
      MT was used to randomize patients and call for initial study cooler. In this
      planned subanalysis, the time to MT protocol activation and time to delivery of
      the initial cooler were evaluated. The impact of these times on mortality and
      time to hemostasis were examined using both Wilcoxon rank sum and linear and
      logistic regression. RESULTS: Among 680 patients, the median time from patient
      arrival to MT protocol activation was 9 minutes with a median time from MT
      activation call to delivery of first cooler of 8 minutes. An increase in both
      time to MT activation and time to arrival of first cooler were associated with
      prolonged time to achieving hemostasis (coefficient, 1.09; p = 0.001 and
      coefficient, 1.16; p < 0.001, respectively). Increased time to MT activation and
      time to arrival of first cooler were associated with increased mortality (odds
      ratio [OR], 1.02; p = 0.009 and OR, 1.02; p = 0.012, respectively). Controlling
      for injury severity, physiology, resuscitation intensity, and treatment arm
      (1:1:1 vs. 1:1:2), increased time to arrival of first cooler was associated with
      an increased mortality at 24 hours (OR, 1.05; p = 0.035) and 30 days (OR, 1.05, p
      = 0.016). CONCLUSION: Delays in MT protocol activation and delays in initial
      cooler arrival were associated with prolonged time to achieve hemostasis and an
      increase in mortality. Independent of products ratios, every minute from time of
      MT protocol activation to time of initial cooler arrival increases odds of
      mortality by 5%. LEVEL OF EVIDENCE: Prognostic, level II; Therapeutic, level III.

PMID- 28452871
TI  - Paying it forward: Four-year analysis of the Eastern Association for the Surgery
      of Trauma Mentoring Program.
AB  - BACKGROUND: Mentorship programs in surgery are used to overcome barriers to
      clinical and academic productivity, research success, and work-life balance. We
      sought to determine if the Eastern Association for the Surgery of Trauma (EAST)
      Mentoring Program has met its goals of fostering academic and personal growth in
      young acute care surgeons. METHODS: We conducted a systematic program evaluation
      of EAST Mentoring Program's first 4 years. Demographic information was collected
      from EAST records, mentorship program applications, and mentee-mentor career
      development plans. We reviewed the career development plans for thematic
      commonalities and results of a structured, online questionnaire distributed since
      program inception. A mixed methods approach was used to better understand the
      program goals from both mentee and mentor perspectives, as well as attitudes and
      barriers regarding the perceived success of this career development program.
      RESULTS: During 2012 to 2015, 65 mentoring dyads were paired and 60 completed the
      program. Of 184 surveys distributed, 108 were returned (57% response rate).
      Respondents were evenly distributed between mentees and mentors (53 vs. 55, p =
      0.768). In participant surveys, mentoring relationships were viewed to focus on
      research (45%), "sticky situations" (e.g., communication, work-life balance)
      (27%), education (18%), or administrative issues (10%). Mentees were more focused
      on research and education versus mentors (74% vs. 50%; p = 0.040). Mentees felt
      that goals were "always" or "usually" met versus mentors (89% vs. 77%; p =
      0.096). Two barriers to successful mentorship included time and communication,
      with most pairs communicating by email. Most respondents (91%) planned to
      continue the relationship beyond the EAST Mentoring Program and recommended the
      experience to colleagues. CONCLUSION: Mentee satisfaction with the EAST Mentoring
      Program was high. Mentoring is a beneficial tool to promote success among EAST's
      young members, but differences exist between mentee and mentor perceptions.
      Revising communication expectations and time commitment to improve career
      development may help our young acute care surgeons.

PMID- 28452872
TI  - Combination therapy of levetiracetam and gabapentin against nonconvulsive
      seizures induced by penetrating traumatic brain injury.
AB  - BACKGROUND: Posttraumatic seizures are a medical problem affecting patients with
      traumatic brain injury. Yet effective treatment is lacking owing to the
      limitations of antiepileptic drugs (AEDs) applicable to these patients. METHODS:
      In this study, we evaluated the dose-response efficacy of levetiracetam (12.5
      100.0 mg/kg) and gabapentin (1.25-25.0 mg/kg) administered either individually or
      in pairs at fixed-dose ratios as a combination in mitigating posttraumatic
      nonconvulsive seizures induced by severe penetrating ballistic-like brain injury
      (PBBI) in rats. Seizures were detected by continuous electroencephalogram (EEG)
      monitoring for 72 hours postinjury. Animals were treated twice per day for 3 days
      by intravenous injections. RESULTS: Both levetiracetam (25-100 mg/kg) and
      gabapentin (6.25-25 mg/kg) significantly reduced PBBI-induced seizure frequency
      by 44% to 73% and 61% to 69%, and seizure duration by 45% to 64% and 70% to 78%,
      respectively. However, the two drugs manifested different dose-response profiles.
      Levetiracetam attenuated seizure activity in a dose-dependent fashion, whereas
      the beneficial effects of gabapentin plateaued across the three highest doses
      tested. Combined administration of levetiracetam and gabapentin mirrored the more
      classic dose-response profile of levetiracetam monotherapy. However, no
      additional benefit was derived from the addition of gabapentin. Furthermore,
      isobolographic analysis of the combination dose-response profile of levetiracetam
      and gabapentin failed to reach the expected level of additivity, suggesting an
      unlikelihood of favorable interactions between these two drugs against
      spontaneously occurring posttraumatic seizure activities at the particular set of
      dose ratios tested. CONCLUSION: This study was the first attempt to apply
      isobolographic approach to studying AED combination therapy in the context of
      spontaneously occurring posttraumatic seizures. Despite the failure to achieve
      additivity from levetiracetam and gabapentin combination, it is important to
      recognize the objectivity of the isobolographic approach in the evaluation of AED
      combination therapy against seizures directly associated with brain injuries.

PMID- 28452873
TI  - Platelet and coagulation function before and after burn and smoke inhalation
      injury in sheep.
AB  - BACKGROUND: Smoke inhalation and burn injury remain a major source of morbidity
      and mortality. There is known dysregulation of hemostasis in burn patients, but
      either hypercoagulation or hypocoagulation states are reported. Sheep are an
      established animal model for studying burn pathology and provide robust data on
      hemostatic function at baseline and after injury. METHODS: After an IACUC
      approved protocol, 15 sheep were anesthetized and subjected to a 40% full
      thickness burn with smoke inhalation. Blood was sampled at baseline, 1 day
      postinjury (early effects) and days 2, 3, and 4 (late effects) after injury.
      Assays at each timepoint assessed: hemostatic function by thromboelastography
      (TEG), platelet counts and function by flow cytometry and aggregometry,
      coagulation protein levels, and free hemoglobin. Data were analyzed by the
      Wilcoxon paired test (nonparametric) with significance set at less than 0.05.
      RESULTS: By 24 hours postinjury, platelet counts had dropped, whereas the percent
      activated platelets increased. Absolute platelet functional response to the
      agonist adenosine diphosphate (ADP) decreased, whereas response to collagen
      showed no significant difference. On a per platelet basis, ADP response was
      unchanged, whereas the collagen response was elevated. Prothrombin time and
      activated partial thromboplastin time were prolonged. TEG parameters decreased
      significantly from baseline. Fibrinogen and factor V were trending up;
      coagulation proteins ATIII, factors IX and X were decreased.Late effects were
      followed in six animals. At day 4, platelet counts remained depressed compared
      with baseline with a nadir at day 2; responses to agonist on a per platelet basis
      remained the same for ADP and stayed elevated for collagen. Platelets continued
      to have elevated activation levels. Fibrinogen and factor V remained
      significantly elevated, whereas TEG parameters and prothrombin time, factors IX
      and X returned to near baseline levels. CONCLUSION: Coagulation parameters and
      hemostasis are dysregulated in sheep after smoke inhalation and burn. By 24
      hours, sheep were hypocoagulable and subsequently became hypercoagulable by day
      4. These results suggest a three-stage coagulopathy in burn injuries with a known
      early consumptive hypercoagulable state which is followed by a relatively
      hypocoagulable state with increased bleeding risk and then a return to a
      relatively unknown hypercoagulability with increased susceptibility to thrombotic
      disorders.

PMID- 28452874
TI  - A retrievable rescue stent graft and radiofrequency positioning for rapid control
      of noncompressible hemorrhage.
AB  - BACKGROUND: Noncompressible hemorrhage of the torso remains a challenging
      surgical dilemma. Stent graft repair requires endovascular expertise, imaging,
      and inventory that are not available within the critical window of massive
      hemorrhage. We developed a retrievable stent graft for rapid hemorrhage. We
      further investigated a radiofrequency (RF) positioning approach as a possible
      alternative to the logistics of fluoroscopy. METHODS: A retrievable stent graft
      was constructed with a novel "petal and stem" design from nitinol and covered
      with a sleeve of electrospun polyurethane. The stent graft was tested using an in
      vitro model of simulated hemorrhage. Next, the stent graft was examined in vivo
      using a porcine model of noncompressible hemorrhage. The stent was examined for
      hemorrhage control in a porcine model of either aortic or caval injury. An RF
      reader was assembled from an Arduino processor while RF tags were affixed to the
      ends of the stent graft. Detection accuracy of a handheld RF wand for an RF tag
      was quantified both in vitro and through tissue. RESULTS: The retrievable
      RESCUEstent graft was deployed within minutes and rapidly controlled traumatic
      hemorrhage angiographically in both aortic injury (n = 3) and caval injury (n =
      2). Stent grafts were easily recaptured in both models in under 15 seconds. The
      LED light of a handheld RF detector illuminated when positioned directly over an
      RF tag. The RF detection approach revealed positioning accuracy to within 1 cm of
      the intended target, despite tissue interference. CONCLUSION: This study
      demonstrates the rapid deployment and retrieval of a RESCUE stent graft as well
      as the ability to tamponade injuries of the aorta and cava. In addition, this
      study demonstrates the feasibility of RF tags to guide stent placement through
      tissue. More rigorous models are needed to define the effectiveness of this
      approach in the setting of vascular injury and shock.

PMID- 28452876
TI  - Leukocyte filtration lesion impairs functional coagulation in banked whole blood.
AB  - BACKGROUND: Whole blood (WB) transfusion is a promising alternative to component
      therapy in hemostatic resuscitation. Use of banked WB requires filtration of
      white blood cells (leukoreduction) and an established shelf life during which WB
      retains coagulant capacities. The goal of this study was to define the time
      course of coagulation stability in leukoreduced compared to unfiltered WB under
      standard refrigeration conditions. METHODS: Twelve WB units were donated by
      healthy volunteers after routine screening. Five units underwent standard
      leukocyte filtration and five did not. Two units were aliquoted into filtered and
      unfiltered samples, with platelets added to each sample on day 14. Units were
      stored at 4 degrees C and sampled on days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28,
      and 35 for immediate thromboelastography (TEG) analysis, and centrifuged and
      stored at -80 degrees C for later calibrated automated thrombogram and
      coagulation factor assays. RESULTS: K-dependent factors and fibrinogen were low
      normal, decreased slightly over 35 days and were similar between unfiltered and
      filtered units. Labile factors were better preserved in filtered units, although
      unfiltered units did not show impaired coagulation over 35 days. Filtered blood
      had delayed clot initiation on days 0, 1, and 2 as measured by TEG R (p < 0.021);
      slower clot progression (TEG alpha-angle) on days 0, 1, 2, 3, 4, 5, and 6 (p <
      0.023); weaker final clot (TEG MA) on all days (p < 0.0001). Thrombin generation
      was delayed on day 28 (p = 0.046) and decreased on days 10, 21, 28, and 35 (p <
      0.034). Addition of platelets to filtered WB rescued TEG MA. CONCLUSION: Filtered
      WB had decreased functional clotting capacity and thrombin generation and may not
      be suitable for hemostatic resuscitation as the sole blood product. LEVEL OF
      EVIDENCE: Therapeutic, level IV.

PMID- 28452877
TI  - Incompatible type A plasma transfusion in patients requiring massive transfusion
      protocol: Outcomes of an Eastern Association for the Surgery of Trauma
      multicenter study.
AB  - : With a relative shortage of type AB plasma, many centers have converted to type
      A plasma for resuscitation of patients whose blood type is unknown. The goal of
      this study is to determine outcomes for trauma patients who received incompatible
      plasma transfusions as part of a massive transfusion protocol (MTP). METHODS: As
      part of an Eastern Association for the Surgery of Trauma multi-institutional
      trial, registry and blood bank data were collected from eight trauma centers for
      trauma patients (age, >= 15 years) receiving emergency release plasma
      transfusions as part of MTPs from January 2012 to August 2016. Incompatible type
      A plasma was defined as transfusion to patient blood type B or type AB. RESULTS:
      Of the 1,536 patients identified, 92% received compatible plasma transfusions and
      8% received incompatible type A plasma. Patient characteristics were similar
      except for greater penetrating injuries (48% vs 36%; p = 0.01) in the
      incompatible group. In the incompatible group, patients were transfused more
      plasma units at 4 hours (median, 9 vs. 5; p < 0.001) and overall for stay (11 vs.
      9; p = 0.03). No hemolytic transfusion reactions were reported. Two transfusion
      related acute lung injury events were reported in the compatible group. Between
      incompatible and compatible groups, there was no difference in the rates of acute
      respiratory distress syndrome (6% vs. 8%; p = 0.589), thromboembolic events (9%
      vs. 7%; p = 0.464), sepsis (6% vs. 8%; p = 0.589), or acute renal failure (8% vs.
      8%, p = 0.860). Mortality at 6 (17% vs. 15%, p = 0.775) and 24 hours (25% vs.
      23%, p = 0.544) and at 28 days or discharge (38% vs. 35%, p = 0.486) were similar
      between groups. Multivariate regression demonstrated that Injury Severity Score,
      older age and more red blood cell transfusion at 4 hours were independently
      associated with death at 28 days or discharge; Injury Severity Score and more red
      blood cell transfusion at 4 hours were predictors for morbidity. Incompatible
      transfusion was not an independent determinant of mortality or morbidity.
      CONCLUSION: Transfusion of type A plasma to patients with blood groups B and AB
      as part of a MTP does not appear to be associated with significant increases in
      morbidity or mortality. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 28452878
TI  - Inefficacy of standard vital signs for predicting mortality and the need for
      prehospital life-saving interventions in blunt trauma patients transported via
      helicopter: A repeated call for new measures.
AB  - BACKGROUND: The aim of this study was to investigate the efficacy of traditional
      vital signs for predicting mortality and the need for prehospital lifesaving
      interventions (LSIs) in blunt trauma patients requiring helicopter transport to a
      Level I trauma center. Our hypothesis was that standard vital signs are not
      sufficient for identifying or determining treatment for those patients most at
      risk. METHODS: This study involved prehospital trauma patients suffering from
      blunt trauma (motor vehicle/cycle collision) and transported from the point of
      injury via helicopter. Means and standard deviations for vital signs and Glasgow
      Coma Scale (GCS) scores were obtained for non-LSI versus LSI and survivor versus
      nonsurvivor patient groups and then compared using Wilcoxon statistical tests.
      Variables with statistically significant differences between patient groups were
      then used to develop multivariate logistic regression models for predicting
      mortality and/or the need for prehospital LSIs. Receiver-operating characteristic
      (ROC) curves were also obtained to compare these models. RESULTS: A final cohort
      of 195 patients was included in the analysis. Thirty (15%) patients received a
      total of 39 prehospital LSIs. Of these, 12 (40%) died. In total, 33 (17%)
      patients died. Of these, 21 (74%) did not receive prehospital LSIs. Model
      variables were field heart rate, lowest systolic blood pressure, shock index,
      pulse pressure, and GCS components. Using vital signs alone, ROC curves
      demonstrated poor prediction of LSI needs, mortality, and nonsurvivors who did
      not receive LSIs (area under the curve [AUC], AUCs: 0.72, 0.65, and 0.61). When
      using both vital signs and GCS, ROC curves still demonstrated poor prediction of
      nonsurvivors overall and nonsurvivors who did not receive LSIs (AUCs: 0.67,
      0.74). CONCLUSION: The major implication of this study was that traditional vital
      signs cannot identify or determine treatment for many prehospital blunt trauma
      patients who are at great risk. This study reiterated the need for new measures
      to improve blunt trauma triage and prehospital care. LEVEL OF EVIDENCE:
      Therapeutic/care management, level IV.

PMID- 28452879
TI  - Aeromedical evacuation-relevant hypobaria worsens axonal and neurologic injury in
      rats after underbody blast-induced hyperacceleration.
AB  - BACKGROUND: Occupants of military vehicles targeted by explosive devices often
      suffer from traumatic brain injury (TBI) and are typically transported by the
      aeromedical evacuation (AE) system to a military medical center within a few
      days. This study tested the hypothesis that exposure of rats to AE-relevant
      hypobaria worsens cerebral axonal injury and neurologic impairment caused by
      underbody blasts. METHODS: Anesthetized adult male rats were secured within
      cylinders attached to a metal plate, simulating the hull of an armored vehicle.
      An explosive located under the plate was detonated, resulting in a peak vertical
      acceleration force on the plate and occupant rats of 100G. Rats remained under
      normobaria or were exposed to hypobaria equal to 8,000 feet in an altitude
      chamber for 6 hours, starting at 6 hours to 6 days after blast. At 7 days, rats
      were tested for vestibulomotor function using the balance beam walking task and
      euthanized by perfusion. The brains were then analyzed for axonal fiber injury.
      RESULTS: The number of internal capsule silver-stained axonal fibers was greater
      in animals exposed to 100G blast than in shams. Animals exposed to hypobaria
      starting at 6 hours to 6 days after blast exhibited more silver-stained fibers
      than those not exposed to hypobaria. Rats exposed to 100% oxygen (O2) during
      hypobaria at 24 hours postblast displayed greater silver staining and more
      balance beam foot-faults, in comparison with rats exposed to hypobaria under 21%
      O2. CONCLUSION: Exposure of rats to blast-induced acceleration of 100G increases
      cerebral axonal injury, which is significantly exacerbated by exposure to
      hypobaria as early as 6 hours and as late as 6 days postblast. Rats exposed to
      underbody blasts and then to hypobaria under 100% O2 exhibit increased axonal
      damage and impaired motor function compared to those subjected to blast and
      hypobaria under 21% O2. These findings raise concern about the effects of AE
      related hypobaria on TBI victims, the timing of AE after TBI, and whether these
      effects can be mitigated by supplemental oxygen.

PMID- 28452880
TI  - Acute and subacute microRNA dysregulation is associated with cytokine responses
      in the rodent model of penetrating ballistic-like brain injury.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small stable RNAs that regulate translational
      degradation or repression of genes involved in brain trauma-mediated
      inflammation. More recently, miRNAs have emerged as potential novel TBI
      biomarkers. The aim of this study was to determine if a select set of miRNAs (miR
      21, Let-7i, miR-124a, miR-146a, miR-107) that were previously associated with TBI
      models and clinical studies would be dysregulated and correlated to inflammatory
      cytokine abundance in the rat penetrating ballistic-like brain injury (PBBI)
      model. METHODS: Adult male Sprague-Dawley rats received a unilateral frontal 10%
      PBBI, which produces a temporary cavity. Sham animals received a craniotomy only.
      Ipsilateral brain tissue and serum were collected 4 hours to 7 days post-injury.
      Quantitation of miR-21, Let-7i, miR-124a, miR-146a, or miR-107 levels was
      conducted using Taqman PCR assays normalized to the endogenous reference, U6
      snRNA. Brain tissue derived from matching cohorts was used to determine 1L-1beta
      and IL-6 levels by enzyme-linked immunosorbent assay. RESULTS: Brain tissue Let
      7i and miR-21 increased at 4 hours and 1 day, whereas miR-124a and miR-107 were
      enhanced only 1 day post-injury. MiR-146a displayed a biphasic response and
      increased 1 day and 7 days, whereas elevation of miR-21 was sustained 1 day to 7
      days after PBBI. Pathway analysis indicated that miRNAs were linked to
      inflammatory proteins, IL-6 and IL-1beta. Confirmation by enzyme-linked
      immunosorbent assay indicated that both cytokines were increased and peaked at 1
      day, but fell at 3 days through 7 days after PBBI, indicating an inverse
      relationship with miRNA abundance. Serum Let-7i, alone, was differentially
      abundant 7 days after PBBI. CONCLUSION: Brain tissue-derived miRNAs linked to
      increased cytokine levels demonstrates a plausible therapeutic target of TBI
      induced inflammation. Suppression of serum derived Let-7i may have utility as a
      biomarker of subacute injury progression or therapeutic responses.

PMID- 28452881
TI  - Differential inflammatory networks distinguish responses to bone marrow-derived
      versus adipose-derived mesenchymal stem cell therapies in vascularized composite
      allotransplantation.
AB  - BACKGROUND: Vascularized composite allotransplantation (VCA) is aimed at enabling
      injured individuals to return to their previous lifestyles. Unfortunately, VCA
      induces an immune/inflammatory response, which mandates lifelong, systemic
      immunosuppression, with attendant detrimental effects. Mesenchymal stem cells
      (MSC)-both adipose-derived (AD-MSC) and bone marrow-derived (BM-MSC)-can
      reprogram inflammation and have been suggested as an alternative to
      immunosuppression, but their mechanism of action is as yet not fully elucidated.
      We sought to gain insights into these mechanisms using a systems biology
      approach. METHODS: PKH26 (red) dye-labeled AD-MSC or BM-MSC were administered
      intravenously to Lewis rat recipients of mismatched Brown-Norway hindlimb
      transplants. Short course tacrolimus (FK-506) monotherapy was withdrawn at
      postoperative day 21. Sera were collected at 4 weeks, 6 weeks, and 18 weeks;
      assayed for 29 inflammatory/immune mediators; and the resultant data were
      analyzed using Dynamic Network Analysis (DyNA), Dynamic Bayesian Network (DyBN)
      inference, and Principal Component Analysis. RESULTS: DyNA network complexity
      decreased with time in AD-MSC rats, but increased in BM-MSC rats. DyBN and
      Principal Component Analysis suggested mostly different central nodes and
      principal characteristics, respectively, in AD-MSC versus BM-MSC rats.
      CONCLUSION: AD-MSC and BM-MSC are associated with both overlapping and distinct
      dynamic networks and principal characteristics of inflammatory/immune mediators
      in VCA grafts with short-course tacrolimus induction therapy. The decreasing
      inflammatory complexity of dynamic networks in the presence of AD-MSC supports
      the previously suggested role for T regulatory cells induced by AD-MSC. The
      finding of some overlapping and some distinct central nodes and principal
      characteristics suggests the role of key mediators in the response to VCA in
      general, as well as potentially differential roles for other mediators ascribed
      to the actions of the different MSC populations. Thus, combined in vivo/in silico
      strategies may yield novel means of optimizing MSC therapy for VCA.

PMID- 28452885
TI  - Optimization of brain metabolism using metabolic-targeted therapeutic hypothermia
      can reduce mortality from traumatic brain injury.
AB  - BACKGROUND: Therapeutic hypothermia is widely used to treat traumatic brain
      injuries (TBIs). However, determining the best hypothermia therapy strategy
      remains a challenge. We hypothesized that reducing the metabolic rate, rather
      than reaching a fixed body temperature, would be an appropriate target because
      optimizing metabolic conditions especially the brain metabolic environment may
      enhance neurologic protection. A pilot single-blind randomized controlled trial
      was designed to test this hypothesis, and a nested metabolomics study was
      conducted to explore the mechanics thereof. METHODS: Severe TBI patients (Glasgow
      Coma Scale score, 3-8) were randomly divided into the metabolic-targeted
      hypothermia treatment (MTHT) group, 50% to 60% rest metabolic ratio as the
      hypothermia therapy target, and the body temperature-targeted hypothermia
      treatment (BTHT) control group, hypothermia therapy target of 32 degrees C to 35
      degrees C body temperature. Brain and circulatory metabolic pool blood samples
      were collected at baseline and on days 1, 3, and 7 during the hypothermia
      treatment, which were selected randomly from a subgroup of MTHT and BTHT groups.
      The primary outcome was mortality. Using H nuclear magnetic resonance technology,
      we tracked and located the disturbances of metabolic networks. RESULTS: Eighty
      eight severe TBI patients were recruited and analyzed from December 2013 to
      December 2014, 44 each were assigned in the MTHT and BTHT groups (median age, 42
      years; 69.32% men; mean Glasgow Coma Scale score, 6.17 +/- 1.02). The mortality
      was significantly lower in the MTHT than the BTHT group (15.91% vs. 34.09%; p =
      0.049). From these, eight cases of MTHT and six cases from BTHT group were
      enrolled for metabolomics analysis, which showed a significant difference between
      the brain and circulatory metabolic patterns in MTHT group on day 7 based on the
      model parameters and scores plots. Finally, metabolites representing potential
      neuroprotective monitoring parameters for hypothermia treatment were identified
      through H nuclear magnetic resonance metabolomics. CONCLUSION: MTHT can
      significantly reduce the mortality of severe TBI patients. Metabolomics research
      showed that this strategy could effectively improve brain metabolism, suggesting
      that reducing the metabolic rate to 50% to 60% should be set as the hypothermia
      therapy target. LEVEL OF EVIDENCE: Therapeutic study, Level I.

PMID- 28452883
TI  - Kaolin-based hemostatic dressing improves hemorrhage control from a penetrating
      inferior vena cava injury in coagulopathic swine.
AB  - BACKGROUND: Retrohepatic inferior vena cava (RIVC) injuries are often lethal due
      to challenges in obtaining hemorrhage control. We hypothesized that packing with
      a new kaolin-based hemostatic dressing (Control+; Z-Medica, Wallingford, CT)
      would improve hemorrhage control from a penetrating RIVC injury compared with
      packing with standard laparotomy sponges alone. METHODS: Twelve male Yorkshire
      pigs received a 25% exchange transfusion of blood for refrigerated normal saline
      to induce a hypothermic coagulopathy. A laparotomy was performed and a
      standardized 1.5 cm injury to the RIVC was created which was followed by
      temporary abdominal closure and a period of uncontrolled hemorrhage. When the
      mean arterial pressure reached 70% of baseline, demonstrating hemorrhagic shock,
      the abdomen was re-entered, and the injury was treated with perihepatic packing
      using standard laparotomy sponges (L; n = 6) or a new kaolin-based hemostatic
      dressing (K; n = 6). Animals were then resuscitated for 6 hours with crystalloid
      solution. The two groups were compared using the Wilcoxon rank sum test and
      Fisher exact test. A p value of 0.05 or less was considered statistically
      significant. RESULTS: There was no difference in the animal's temperature, heart
      rate, mean arterial pressure, cardiac output, and blood loss at baseline or
      before packing was performed (all p > 0.05). In the laparotomy sponge group, five
      of six pigs survived the entire study period, whereas all six pigs treated with
      kaolin-based D2 hemostatic dressings survived. Importantly, there was
      significantly less blood loss after packing with the new hemostatic kaolin-based
      dressing compared with packing with laparotomy sponge (651 +/- 180 mL vs. 1073 +/
      342 mL; p <= 0.05). CONCLUSION: These results demonstrate that the use of this
      new hemostatic kaolin-based dressing improved hemorrhage control and
      significantly decreased blood loss in this penetrating RIVC model. LEVEL OF
      EVIDENCE: This is basic science research based on a large animal model, level V.

PMID- 28452886
TI  - Platelet transfusions reduce fibrinolysis but do not restore platelet function
      during trauma hemorrhage.
AB  - BACKGROUND: Platelets play a critical role in hemostasis with aberrant function
      implicated in trauma-induced coagulopathy. However, the impact of massive
      transfusion protocols on platelet function during trauma hemorrhage is unknown.
      The aim of this study was to characterize the effects of platelet transfusion on
      platelet aggregation and fibrinolytic markers during hemostatic resuscitation.
      METHODS: Trauma patients enrolled into the prospective Activation of Coagulation
      and Inflammation in Trauma study between January 2008 and November 2015 who
      received at least four units of packed red blood cells (PRBCs) were included.
      Blood was drawn in the emergency department within 2 hours of injury and at
      intervals after every four units of PRBCs transfused. Platelet aggregation was
      assessed in whole blood with multiple electrode aggregometry. Plasma proteins
      were quantified by enzyme-linked immunosorbent assay. RESULTS: Of 161 patients
      who received four or more PRBCs as part of their initial resuscitation, 44
      received 8 to 11 units and 28 received 12 units or more. At each timepoint during
      bleeding, platelet aggregation was similar in patients who had received a
      platelet transfusion compared with those who had only received other blood
      products (p > 0.05 for all timepoints). Platelet transfusion during the four PRBC
      intervals was associated with a decrease in maximum lysis on rotational
      thromboelastometry (start of interval, 6% [2-12] vs. end of interval, 2% [0-5]; p
      = 0.001), an increase in plasminogen activator inhibitor-1 (start of interval,
      35.9 +/- 14.9 vs. end of interval, 66.7 +/- 22.0; p = 0.007) and a decrease in
      tissue plasminogen activator (start of interval, 26.2 +/- 10.5 vs. end of
      interval, 19.0 +/- 5.1; p = 0.04). No statistically significant changes in these
      parameters occurred in intervals which did not contain platelets. CONCLUSION:
      Current hemostatic resuscitation strategies do not appear to restore platelet
      aggregation during active hemorrhage. However, stored platelets may attenuate
      fibrinolysis by providing an additional source of plasminogen activator inhibitor
      1. Further investigation into the effects of early platelet transfusion on
      platelet function, hemostatic, and clinical outcomes during bleeding are
      warranted. LEVEL OF EVIDENCE: Therapeutic, level III.

PMID- 28452888
TI  - The impact of patient weight on burn resuscitation.
AB  - BACKGROUND: Optimal fluid resuscitation of burn patients with burns greater than
      20% total body surface area is critical to prevent burn shock during the initial
      24 hours to 48 hours postburn. Currently, most resuscitation formulas incorporate
      the patient's weight when estimating 24-hour fluid requirements. The objective of
      this study was to determine the impact of weight on fluid resuscitation
      requirements and outcomes during the initial 24 hours after admission. METHODS:
      We performed a retrospective review of patients admitted to our burn intensive
      care unit from December 2007 to April 2013, resuscitated with a computerized
      decision support system. We classified patients into body mass index (BMI)
      categories of underweight (BMI: <18.5), normal (BMI: 18.5-24.9), overweight (BMI:
      25.0-29.9), or obese (BMI: >30.0). We also calculated the percent difference from
      ideal body weight (IBW) and compared 24-hour fluid volumes received. RESULTS:
      Patients with missing weight and/or height values were excluded from the study,
      resulting in a final cohort of 161 patients for analysis. Mean total body surface
      area was 42 +/- 20% with a full thickness burn of 18 +/- 23%. Mean age, weight,
      and height were 47 +/- 19 years, 83 +/- 19 kg, and 68 +/- 4 inches, respectively.
      IBW for this cohort was 68 +/- 11 kg with a BMI of 28 +/- 6. Univariate analysis
      showed significant differences in 24-hour resuscitation volumes (mL/kg) between
      normal and obese patients (p < 0.05). Further analysis revealed that increasing
      percent difference from IBW was associated with lower fluid volumes. Although
      obesity was not associated with inhalation injury or renal replacement therapy,
      it was correlated to an increased risk for mortality (p < 0.05). CONCLUSION: This
      analysis showed that increasing weight was associated with lower fluid
      resuscitation volume requirements and a higher mortality rate, despite the low
      incidence of inhalation injury and renal replacement therapy in our obese
      patients. The use of actual body weight to drive resuscitation volumes may result
      in overresuscitation of obese patients, depending on the resuscitation formula.
      Further studies are needed to better explain the relationship between mortality
      and obesity in burn patients. LEVEL OF EVIDENCE: Therapeutic/care management,
      level IV.

PMID- 28452889
TI  - Surgical management of pancreatic necrosis: A practice management guideline from
      the Eastern Association for the Surgery of Trauma.
AB  - BACKGROUND: Pancreatic or peripancreatic tissue necrosis confers substantial
      morbidity and mortality. New modalities have created a wide variation in
      approaches and timing of interventions for necrotizing pancreatitis. As acute
      care surgery evolves, its practitioners are increasingly being called upon to
      manage these complex patients. METHODS: A systematic review of the MEDLINE
      database using PubMed was performed. English language articles regarding
      pancreatic necrosis from 1980 to 2014 were included. Letters to the editor, case
      reports, book chapters, and review articles were excluded. Topics of
      investigation included operative timing, the use of adjuvant therapy and the type
      of operative repair. Grading of Recommendations, Assessment, Development and
      Evaluations methodology was applied to question development, outcome
      prioritization, evidence quality assessments, and recommendation creation.
      RESULTS: Eighty-eight studies were included and underwent full review. Increasing
      the time to surgical intervention had an improved outcome in each of the periods
      evaluated (72 hours, 12-14 days, 30 days) with a significant improvement in
      outcomes if surgery was delayed 30 days. The use of percutaneous and endoscopic
      procedures was shown to postpone surgery and potentially be definitive. The use
      of minimally invasive surgery for debridement and drainage has been shown to be
      safe and associated with reduced morbidity and mortality. CONCLUSION: Acute Care
      Surgeons are uniquely trained to care for those with pancreatic necrosis due
      their training in critical care and complex surgery with ongoing shock. In adult
      patients with pancreatic necrosis, we recommend that pancreatic necrosectomy be
      delayed until at least day 12. During the first 30 days of symptoms with infected
      necrotic collections, we conditionally recommend surgical debridement only if the
      patients fail to improve after radiologic or endoscopic drainage. Finally, even
      with documented infected necrosis, we recommend that patients undergo a step-up
      approach to surgical intervention as the preferred surgical approach. LEVEL OF
      EVIDENCE: Systematic review/guideline, level III.

PMID- 28452890
TI  - Comparison of nonoperative and surgical management of renal trauma.

PMID- 28452891
TI  - Child seat belt guidelines: Examining the 4 feet 9 inches rule as the standard.
AB  - BACKGROUND: Current American Academy of Pediatrics recommendations regarding
      transition from child safety/booster seat to adult safety belt use indicate that
      children should be at least 4 feet 9 inches, 8 years old, or 80 pounds. Proper
      fit in the vehicle seat, assessed with a five-point fit test, should also be met.
      Although most children reach 4 feet 9 inches around age 8 years, each child and
      vehicle presents a unique combination; thus a child may not fit appropriately in
      all vehicle types using only the 4 feet 9 inches requirement. METHODS: We
      enrolled children, aged 7 years to 12 years, into our study. Height, weight, and
      demographic data were obtained. A Child Passenger Safety Technician then
      performed the five-point fit test in each of a uniform lineup of five vehicles.
      Data were collected on fit in the standard vehicle seat and also in a booster
      seat. We set 90% as the threshold proportion of children who meet all criteria
      for proper fit to validate current recommendations of a height of 4 feet 9
      inches. RESULTS: Data were collected on 388 children. The percentage of 90%
      proper fit was met in the compact car and small sport-utility vehicle (SUV).
      However, only 80 (77%) of 104 students (p < 0.0001) that were 4 feet 9 inches or
      higher fit properly in the large SUV, only 87 (83%) of 105 students (p = 0.02)
      fit properly in the pickup truck, and only 91 (89%) of 102 students (p = 0.74)
      fit properly in the minivan. CONCLUSION: Substantial proportions of children
      meeting current height guidelines for an adult seat belt do not meet safety
      requirements for fit, especially in larger, commonly used vehicles (large SUVs
      and trucks). This emphasizes the need for evaluation of fit by a trained
      personnel and/or development of standard back seat dimensions in all vehicles for
      maximum safety. LEVEL OF EVIDENCE: Epidemiologic study, level III; Therapeutic
      study, level V.

PMID- 28452892
TI  - Re: Comparison of nonoperative and surgical management of renal trauma.

PMID- 28452893
TI  - Early unplanned trauma readmissions in a safety net hospital are resource
      intensive but not due to resource limitations.
AB  - BACKGROUND: In an era of decreasing reimbursements, the incentive to decrease
      readmissions has never been greater. It has been suggested that trauma
      readmission is an indicator of poor hospital care or fragmented discharge. Even
      though trauma readmissions are relatively low, readmissions add significant cost,
      tie up already limited resources and lead to worse outcomes, including mortality.
      The literature on trauma readmissions is sparse, and the reasons and risk factors
      for readmission are inconsistent across studies. If readmissions are to serve as
      useful indicators of quality of care, we must elucidate factors that may predict
      readmissions. METHODS: We performed a retrospective review of all admissions to
      our urban Level I trauma center from July 1, 2012, to June 30, 2015. All patients
      aged 16 years or older who were discharged alive were included. We identified all
      unplanned readmissions that occurred within 30 days of discharge and performed an
      extensive chart review to determine the reasons for readmission. We performed
      univariate and multivariable analyses. RESULTS: We identified 6,026 index trauma
      admissions, with 158 (2.6%) unplanned readmissions within 30 days of discharge.
      The most common reasons for readmission were disease/symptom progression (30.2%),
      wound complications (28.9%), and pain control (11.8%). On multivariate analysis,
      only Injury Severity Score (odds ratio [OR], 1.02; 95% confidence interval [CI],
      1.00-1.05; p=0.016), penetrating injuries (OR, 1.9; 95% CI, 1.12-3.24; p=0.018),
      and smoking (OR, 1.73; 95% CI, 1.05-2.86; p=0.031) were found to be significant.
      Hospital length of stay, insurance status, and race were not significant.
      CONCLUSION: In a resource-limited environment, we expected a lack of access to
      care would lead to increased trauma readmissions; however, we were still able to
      achieve similar readmission rates, irrespective of insurance status and race. Our
      trauma readmission rate is low and consistent with previously published studies.
      Our results at our Level I trauma center support previously published studies
      that found Injury Severity Score and penetrating injury to be risk factors for
      readmission; however, more ubiquitous risk factors, such as hospital length of
      stay and discharge destination, were not significant. With no consensus on the
      risk factors for unplanned early trauma readmission, individual trauma centers
      should evaluate their specific risk factors for readmission to improve patient
      outcomes and decrease hospital costs. LEVEL OF EVIDENCE: Care management, level
      IV; Epidemiologic, level IV.

PMID- 28452895
TI  - C-peptide attenuates acute lung inflammation in a murine model of hemorrhagic
      shock and resuscitation by reducing gut injury.
AB  - BACKGROUND: The study aims to evaluate whether C-peptide can reduce gut injury
      during hemorrhagic shock (HS) and resuscitation (R) therefore attenuate shock
      induced inflammation and subsequent acute lung injury. METHODS: Twelve-week-old
      male mice (C57/BL6) were hemorrhaged (mean arterial blood pressure maintained at
      35 mm Hg for 60 minutes) and then resuscitated with Ringer's lactate, followed by
      red blood cell transfusion with (HS/R) or without C-peptide (HS/R + C-peptide).
      Mouse gut permeability, bacterial translocation into the circulatory system and
      intestinal pathology, circulating HMGB1, and acute lung injury were assessed at
      different times after R. The mice in the control group underwent sham procedures
      without HS. RESULTS: Compared to the sham group, the mice in the HS/R group
      showed increased gut permeability (6.07 +/- 3.41 MUg of FD4/mL) and bacterial
      translocation into the circulatory system (10.05 +/- 4.92, lipopolysaccharide
      [LPS] of pg/mL), and increased gut damage; conversely, mice in the HS/R + C
      peptide group showed significantly reduced gut permeability (1.59 +/- 1.39 MUg of
      FD4/mL; p < 0.05) and bacterial translocation (4.53 +/- 1.08 pg of LPS/mL; p <
      0.05) with reduced intestine damage. In addition, mice in the HS/R group had
      increased circulating HMGB1 (21.64 +/- 14.17 ng/mL), lung myeloperoxidase)
      activity (34.4 +/- 8.91 mU/g of tissue), and pulmonary protein leakage (2.33 +/-
      1.16 MUg Evans blue/g tissue per minute). Mice in the HS/R + C-peptide group
      showed decreased HMGB1 (7.27 +/- 1.93 ng/mL; p < 0.05), lung myeloperoxidase
      (23.73 +/- 8.39 mU/g of tissue; p < 0.05), and pulmonary protein leakage (1.17 +/
      0.42 Evans Blue/g tissue per minute; p < 0.05). CONCLUSION: Our results indicate
      that C-peptide exerts beneficial effects to attenuate gut injury and dysfunction,
      therefore diminishing lung inflammation and subsequent injury in mice with HS and
      R.

PMID- 28452894
TI  - Severe trauma and chronic stress activates extramedullary erythropoiesis.
AB  - BACKGROUND: Severe traumatic injury is associated with bone marrow dysfunction
      that manifests as impaired erythropoiesis and prolonged hematopoietic progenitor
      cell (HPC) mobilization from the bone marrow. Extramedullary erythropoiesis, the
      development of red blood cells outside the bone marrow, has not been studied
      after severe injury and critical illness. This study examined the influence of
      lung contusion/hemorrhagic shock (LCHS) followed by chronic stress (CS) on the
      rodent spleen and to investigate the involvement of the splenic erythropoietin
      (EPO)/EPO receptor and BMP4 signaling. METHODS: Male Sprague-Dawley rats were
      subjected to LCHS and LCHS/CS. Animals underwent 2 hours of daily restraint
      stress until the day of sacrifice. On day 7, the spleen was assessed for weight,
      growth of splenic colony-forming units (CFU)-granulocyte-, erythrocyte-, monocyte
      megakaryocyte (GEMM), burst-forming unit-erythroid (BFU-E), and CFU-E colonies,
      the presence of HPCs, and splenic mRNA expression of bone morphogenetic protein 4
      (BMP4), EPO and its receptor. Data were presented as mean +/- SD; *p < 0.05 vs.
      naive and **p < 0.05 vs. LCHS by t test. RESULTS: On day 7, the addition of CS to
      LCHS increased spleen weight by 22%. LCHS/CS increased splenic growth of CFU
      GEMM, BFU-E, and CFU-E colonies by 28% to 39% versus LCHS alone. Seven days after
      LCHS/CS, splenic HPCs increased from 0.60% to 1.12 % compared with naive animals.
      After LCHS/CS, both BMP4 and EPO expression increased significantly in the
      spleen. Splenic EPO receptor (EPOr) expression decreased after LCHS/CS in the
      presence of a persistent moderate anemia. CONCLUSION: Extramedullary
      erythropoiesis, manifest by increased splenic weight, splenic erythroid colony
      growth, splenic HPCs, BMP4, and EPO expression, is present in the spleen after
      LCHS/CS. Splenic EPOr expression was significantly decreased after LCHS/CS.
      Extramedullary erythropoiesis may play a key role in identifying new therapies to
      aid the recovery from acute anemia after severe trauma and chronic stress.

PMID- 28452896
TI  - Evaluating trauma team performance in a Level I trauma center: Validation of the
      trauma team communication assessment (TTCA-24).
AB  - BACKGROUND: Nontechnical skills (NTS), such as team communication, are well
      recognized determinants of trauma team performance and good patient care.
      Measuring these competencies during trauma resuscitations is essential, yet few
      valid and reliable tools are available. We aimed to demonstrate that the Trauma
      Team Communication Assessment (TTCA-24) is a valid and reliable instrument that
      measures communication effectiveness during activations. METHODS: Two tools with
      adequate psychometric strength (Trauma Nontechnical Skills Scale [T-NOTECHS],
      Team Emergency Assessment Measure [TEAM]) were identified during a systematic
      review of medical literature and compared with TTCA-24. Three coders used each
      tool to evaluate 35 stable and 35 unstable patient activations (defined according
      to Advanced Trauma Life Support criteria). Interrater reliability was calculated
      between coders using the intraclass correlation coefficient. Spearman rank
      correlation coefficient was used to establish concurrent validity between TTCA-24
      and the other two validated tools. RESULTS: Coders achieved an intraclass
      correlation coefficient of 0.87 for stable patient activations and 0.78 for
      unstable activations scoring excellent on the interrater agreement guidelines.
      The median score for each assessment showed good team communication for all 70
      videos (TEAM, 39.8 of 54; T-NOTECHS, 17.4 of 25; and TTCA-24, 87.4 of 96). A
      significant correlation between TTTC-24 and T-NOTECHS was revealed (p = 0.029),
      but no significant correlation between TTCA-24 and TEAM (p = 0.77). Team
      communication was rated slightly better across all assessments for stable versus
      unstable patient activations, but not statistically significant. CONCLUSION: TTCA
      24 correlated with T-NOTECHS, an instrument measuring nontechnical skills for
      trauma teams, but not TEAM, a tool that assesses communication in generic
      emergency settings. TTCA-24 is a reliable and valid assessment that can be a
      useful adjunct when evaluating interpersonal and team communication during trauma
      activations. LEVEL OF EVIDENCE: Diagnostic tests or criteria, level II.

PMID- 28452897
TI  - Are "goods for guns" good for the community? An update of a community gun buyback
      program.
AB  - BACKGROUND: Gun violence remains a leading cause of death in the United States.
      Community gun buyback programs provide an opportunity to dispose of extraneous
      firearms. The purpose of this study was to understand the demographics,
      motivation, child access to firearms, and household mental illness of buyback
      participants in hopes of improving the program's effectiveness. METHODS: A 2015
      Injury Free Coalition for Kids gun buyback program which collaborated with local
      police departments was studied. We administered a 23-item questionnaire survey to
      gun buyback participants assessing demographic characteristics, motivation for
      relinquishing firearms, child firearm accessibility, and mental illness/domestic
      violence history. RESULTS: A total of 186 individuals from Central/Western
      Massachusetts turned in 339 weapons. Participants received between US $25 and US
      $75 in gift cards dependent on what type of gun was turned in, with an average
      cost of $41/gun. A total of 109 (59%) participants completed the survey.
      Respondents were mostly white (99%), men (90%) and first-time participants in the
      program (85.2%). Among survey respondents, 54% turned in firearms "for safety
      reasons." Respondents reported no longer needing/wanting their weapons (47%) and
      approximately one in eight participants were concerned the firearm(s) were
      accessible to children. Most respondents (87%) felt the program encouraged
      neighborhood awareness of firearm safety. Three of every five participants
      reported that guns still remained in their homes; additionally, 21% where
      children could potentially access them and 14% with a history of mental
      illness/suicide/domestic violence in the home. CONCLUSION: Gun buybacks can
      provide a low-cost means of removing unwanted firearms from the community. Most
      participants felt their homes were safer after turning in the firearm(s). In
      homes still possessing guns, emphasis on secure gun storage should continue,
      increasing the safety of children and families. The results of this survey also
      provided new insights into the association between mental illness/suicide and gun
      ownership. LEVEL OF EVIDENCE: Epidemiological, level III.

PMID- 28452898
TI  - Accuracy of prehospital triage protocols in selecting severely injured patients:
      A systematic review.
AB  - BACKGROUND: Prehospital trauma triage ensures proper transport of patients at
      risk of severe injury to hospitals with an appropriate corresponding level of
      trauma care. Incorrect triage results in undertriage and overtriage. The American
      College of Surgeons Committee on Trauma recommends an undertriage rate below 5%
      and an overtriage rate below 50% for prehospital trauma triage protocols. To find
      the most accurate prehospital trauma triage protocol, a clear overview of all
      currently available protocols and corresponding outcomes is necessary.
      OBJECTIVES: The aim of this systematic review was to evaluate the current
      literature on all available prehospital trauma triage protocols and determine
      accuracy of protocol-based triage quality in terms of sensitivity and
      specificity. METHODS: A search of Pubmed, Embase, and Cochrane Library databases
      was performed to identify all studies describing prehospital trauma triage
      protocols before November 2016. The search terms included "trauma," "trauma
      center," or "trauma system" combined with "triage," "undertriage," or
      "overtriage." All studies describing protocol-based triage quality were reviewed.
      To assess the quality of these type of studies, a new critical appraisal tool was
      developed. RESULTS: In this review, 21 articles were included with numbers of
      patients ranging from 130 to over 1 million. Significant predictors for severe
      injury were: vital signs, suspicion of certain anatomic injuries, mechanism of
      injury, and age. Sensitivity ranged from 10% to 100%; specificity from 9% to
      100%. Nearly all protocols had a low sensitivity, thereby failing to identify
      severely injured patients. Additionally, the critical appraisal showed poor
      quality of the majority of included studies. CONCLUSION: This systematic review
      shows that nearly all protocols are incapable of identifying severely injured
      patients. Future studies of high methodological quality should be performed to
      improve prehospital trauma triage protocols. LEVEL OF EVIDENCE: Systematic
      review, level III.

PMID- 28452899
TI  - Cytochrome c and resveratrol preserve platelet function during cold storage.
AB  - BACKGROUND: Donated platelets are stored at 22 degrees C and discarded within 5
      days because of diminished function and risk of bacterial contamination. Decline
      of platelet function has been attributed to decreased mitochondrial function and
      increased oxidative stress. Resveratrol (Res) and cytochrome c (Cyt c), in
      combination with hypothermic storage, may extend platelet viability. METHODS:
      Platelets from 20 donors were pooled into four independent sets and stored at 22
      degrees C or 4 degrees C in the absence or presence of Res (50 MUM) or Cyt c (100
      MUM) for up to 10 days. Sequential measurement of platelet counts, coagulation
      function (thromboelastography), oxygen consumption, lipid peroxidation, glucose
      lactate levels, pH, TCO2, and soluble platelet activation markers (CD62P/PF-4)
      was performed. RESULTS: Platelet function diminished rapidly over time at 22
      degrees C versus 4 degrees C (adenosine diphosphate, day 10 [0.6 +/- 0.5] vs.
      [7.8 +/- 3.5], arachidonic acid: day 10 [0.5 +/- 0.5] vs. [30.1 +/- 27.72]). At 4
      degrees C, storage treatment with Res or Cyt c limited deterioration in platelet
      function up to day 10, an effect not observed at 22 degrees C (day 10, 4 degrees
      C, Con [7.8 +/- 3.5] vs. Res [37.3 +/- 24.19] vs. Cyt c [45.83 +/- 43.06]).
      Mechanistic analysis revealed oxygen consumption increased in response to Cyt c
      at 22 degrees C, whereas neither Cyt c or Res affected oxygen consumption at 4
      degrees C. Lipid peroxidation was only reduced at 22 degrees C (day 7 and day
      10), but remained unchanged at 4 degrees C, or when Res or Cyt c was added.
      Cytosolic ROS was significantly reduced by pretreatment with Res at 4 degrees C.
      Total platelet count and soluble activation markers were unchanged during storage
      and not affected by Res, Cyt c, or temperature. Glucose concentration, pH and
      TCO2 decreased while lactate levels increased during storage at 22 degrees C but
      not 4 degrees C. CONCLUSION: Platelet function is preserved by cold storage for
      up to 10 days. This function is enhanced by treatment with Res or Cyt c, which
      supports mitochondrial activity, thus potentially extending platelet shelf life.

PMID- 28452900
TI  - The Vietnam Vascular Registry at 50 years: An historical perspective and
      continuing legacy.

PMID- 28452901
TI  - Effect of pain and analgesia on compensatory reserve.
AB  - BACKGROUND: The measurement of the body's capacity to compensate for reduced
      blood volume can be assessed with a compensatory reserve measurement (CRM). The
      CRM, which is calculated from changes in features of the arterial waveform,
      represents the integration of compensatory mechanisms during states of low tissue
      perfusion and oxygenation, such as hemorrhage. This study was designed to test
      the hypothesis that pain which activates compensatory mechanisms and analgesia
      that result in reduced blood pressure are associated with lower compensatory
      reserve. This study evaluated CRM in obstetric patients during labor as pain
      intensity increased from no pain to severe pain and compared CRM before and after
      epidural anesthesia. METHODS: CRM was calculated from a finger pulse oximeter
      placed on the patient's index finger and connected to the DataOx monitor in
      healthy pregnant women (n = 20) before and during the active labor phase of
      childbirth. RESULTS: As pain intensity, based on an 11-point scale (0, no pain;
      10, worst pain), increased from 0 to 8.4 +/- 0.9 (mean +/- SD), CRM was not
      affected (81 +/- 10% to 82 +/- 13%). Before analgesia, CRM was 84 +/- 10%. CRM at
      10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, and 60 minutes after
      analgesia was 82 +/- 11%, 83 +/- 14%, 83 +/- 15%, 86 +/- 12%, 89 +/- 9%, and 87
      +/- 10%, respectively. There was a transient 2% reduction followed by a 5%
      increase in CRM from before to after epidural anesthesia (p = 0.048). Pain scores
      before and after analgesia were 7 +/- 2 and 1 +/- 1, respectively (p < 0.001).
      CONCLUSION: These results indicate that pain and analgesia contribute minimally,
      but independently to the reduction in compensatory reserve associated with trauma
      and hemorrhage. As such, our findings suggest that analgesia can be safely
      administered on the battlefield while maintaining the maximal capacity of
      mechanisms to compensate for blood loss. LEVEL OF EVIDENCE: Diagnostic study,
      level II.

PMID- 28452902
TI  - Delirium Associated With Fluoxetine Discontinuation: A Case Report.
AB  - BACKGROUND: Withdrawal symptoms on selective serotonin reuptake inhibitor (SSRI)
      discontinuation have raised clinical attention increasingly. However, delirium is
      rarely reported in the SSRI discontinuation syndrome. CASE: We report a case of
      delirium developing after fluoxetine discontinuation in a 65-year-old female
      patient with major depressive disorder. She experienced psychotic depression with
      limited response to treatment of fluoxetine 40 mg/d and quetiapine 100 mg/d for 3
      months. After admission, we tapered fluoxetine gradually in 5 days because of its
      limited effect. However, delirious pictures developed 2 days after we stopped
      fluoxetine. Three days later, we added back fluoxetine 10 mg/d. Her delirious
      features gradually improved, and the clinical presentation turned into previous
      psychotic depression state. We gradually increased the medication to fluoxetine
      60 mg/d and olanzapine 20 mg/d in the following 3 weeks. Her psychotic symptoms
      decreased, and there has been no delirious picture noted thereafter. CONCLUSIONS:
      Delirium associated with fluoxetine discontinuation is a much rarer complication
      in SSRI discontinuation syndrome. The symptoms of SSRI discontinuation syndrome
      may be attributable to a rapid decrease in serotonin availability. In general,
      the shorter the half-life of any medication, the greater the likelihood patients
      will experience discontinuation symptoms. Genetic vulnerability might be a
      potential factor to explain that SSRI discontinuation syndrome also occurred
      rapidly in people taking long-half-life fluoxetine. The genetic polymorphisms of
      both pharmacokinetic and pharmacodynamic pathways might be potentially associated
      with SSRI discontinuation syndrome.

PMID- 28452903
TI  - Zonisamide in Brain Tumor-Related Epilepsy: An Observational Pilot Study.
AB  - OBJECTIVES: Epilepsy heavily affects the quality of life (QoL) of patients with
      brain tumor because in addition to taking treatments for the oncological illness,
      patients are required to live with the long-term taking of antiepileptic drugs
      (AEDs). The AEDs' adverse effects are common in these patients and can negatively
      influence their perceptions of their QoL.We conducted an observational pilot
      study in patients with brain tumor-related epilepsy to verify efficacy,
      tolerability, and impact on QoL and global neurocognitive performances of
      zonisamide (ZNS) in add-on. MATERIALS AND METHODS: We recruited 13 patients (5
      females, 8 males; mean age, 49.6 years) presenting uncontrolled seizures. At
      first visit and at final follow-up at 6 months, patients underwent neurological
      examination, evaluation of adverse events, and cognitive and QoL tests. A seizure
      diary was given. RESULTS: Eight patients underwent chemotherapy, 3 underwent
      radiotherapy, and 5 had disease progression. Mean dosage of ZNS at final follow
      up was 300 mg/d.Of 9 patients who reached the sixth month follow-up, the mean
      weekly seizure number before ZNS had been 3.2 +/- 5.0, and at final follow-up,
      the mean weekly seizure number was 0.18 +/- 0.41 (P = 0.05).Compared with
      baseline, we observed stability in all cognitive domains, except for verbal
      fluency that significantly worsened.Results on QoL tests showed that QoL remained
      unchanged over time, which could indicate that ZNS did not influence the
      patients' perceived QoL. CONCLUSIONS: Zonisamide as add-on in our patients seems
      to be well tolerated and efficacious in controlling seizures. Despite having
      limitations represented by the fact that our study is observational, with a small
      study population and a short follow-up period, our results confirm that when
      choosing an AED, in addition to efficacy, the drug's effect on patients' QoL also
      needs to be considered, especially for patients facing many psychosocial
      challenges, such as those with brain tumor-related epilepsy.

PMID- 28452904
TI  - A Placebo-Controlled Crossover Trial of Gastrin-Releasing Peptide in Childhood
      Autism.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy, safety, and
      tolerability of gastrin-releasing peptide (GRP) compared with placebo in autism
      spectrum disorder symptoms. METHODOLOGY: This is a randomized, double-blind,
      placebo-controlled crossover trial using GRP 160 pmol/kg for 4 consecutive days
      in 10 children with autism. Outcomes were measured by the Aberrant Behavior
      Checklist (ABC) scale. RESULTS: All participants were boys, aged between 4 and 9
      years. There was a reduction in the scores of the ABC range and its subscales
      after use GRP and placebo. The reduction was more prominent with GRP,
      particularly in the subscale "hyperactivity and noncompliance," but there was no
      statistical difference between the results (P = 0.334). After a week of infusion,
      5 children showed improvement of 25% or greater in the total score of the ABC
      scale with GRP use and 2 with placebo use; however, there was no statistical
      difference (P = 0.375). There were no adverse effects, changes in vital signs, or
      laboratory abnormalities associated with the use of GRP. CONCLUSIONS: The results
      of this study, despite the small sample size, reinforce previous data on the
      safety of the GRP in short-term use. There is a need for further research with
      other designs and a larger sample size to evaluate the efficacy and safety of GRP
      in children with autism.

PMID- 28452905
TI  - Duodenal Levodopa Infusion for Long-Term Deep Brain Stimulation-Refractory
      Symptoms in Advanced Parkinson Disease.
AB  - OBJECTIVES: This study assesses the effect of levodopa/carbidopa intestinal
      infusion gel (LCIIG) as an additional treatment in patients with advanced
      idiopathic Parkinson disease (PD) previously treated with deep brain stimulation
      (DBS). METHODS: Prospective study of advanced PD patients, satisfactorily treated
      with bilateral DBS of the subthalamic nucleus, who had developed refractory
      symptoms and LCIIG was added. Controls were advanced PD patients treated with
      LCIIG. Measurements included the Unified Parkinson Disease Rating Scale (UPDRS)
      III and the UPDRS axial compound. RESULTS: There were 19 patients in the DBS
      LCIIG therapy group and 21 in the control group. The DBS-LCIIG patients were
      younger and had disease duration longer than controls. The median time from DBS
      to gastrostomy was 7.8 years (range, 2-12 years). In both study groups, the mean
      scores of the UPDRS-III and UPDRS axial subscales improved significantly after
      LCIIG treatment (DBS-LCIIG group: UPDRS-III, 62.0 [15.7] vs 30.9 [12.1]; UPDRS
      axial, 24.7 [4.9] vs 10.2 [2.7]; P < 0.0005 for all comparisons). There were no
      differences in adverse events between the groups. In the follow-up of the DBS
      LCIIG group. 5 patients discontinued DBS-LCIIG therapy and returned to DBS, 5
      discontinued DBS and were maintained with LCIIG, and the remaining 9 continued
      with DBS-LCIIG therapy. Mean time until discontinuation in the double DBS-LCIIG
      group was 891 days. The main risk factors for discontinuation were age at the
      beginning of LCIIG and severity of the UPDRS axial subscale. CONCLUSIONS:
      Levodopa/carbidopa intestinal infusion gel therapy may be a valuable option in
      selected patients with advanced PD who develop refractory symptoms after long
      term subthalamic nucleus-DBS.

PMID- 28452906
TI  - Reversible Pisa Syndrome Induced by Rivastigmine in a Patient With Early-Onset
      Alzheimer Disease.
AB  - Pisa syndrome (PS) is a state of dystonic muscle contraction with a marked
      truncal deviation to one side. It is an uncommon adverse effect of antipsychotic
      drugs, but is rarely reported in patients receiving acetylcholinesterase
      inhibitors, especially rivastigmine. We present a 57-year-old female patient with
      Alzheimer disease who began to develop symptoms of dementia at the age of 51
      years. She was observed to have symptoms of PS after continuous use of
      rivastigmine (9 mg/d) for nearly 2 years. The PS symptoms improved after the dose
      of rivastigmine was reduced but recurred when the dose was added back to 9 mg/d.
      Finally, after we decreased the dose to 4.5 mg/d, her PS symptoms were remitted.
      This report reminds us that clinicians need to be cautious about the risk of PS
      when prescribing rivastigmine in a patient with early-onset Alzheimer disease.

PMID- 28452908
TI  - Measurement of Oxygen Consumption Variations in Critically Ill Burns Patients:
      Are the Fick Method and Indirect Calorimetry Interchangeable?
AB  - OBJECTIVES: To evaluate the interchangeability of oxygen consumption variations
      measured with the Fick equation (DeltaVO2Fick) and indirect calorimetry
      (DeltaVO2Haldane) in critically ill burns patients. METHODS: Prospective
      observational single-center study conducted in a university hospital. Twenty-two
      consecutive burns patients with circulatory insufficiency and hyperlactatemia (>2
      mmol/L) who required a fluid challenge (FC) were included. All patients had
      cardiac output monitoring (transpulmonary thermodilution technique) and were
      ventilated and sedated. Simultaneous measurements of VO2Fick and VO2Haldane were
      performed before and immediately after the FC, at rest, and in hemodynamic
      conditions stabilized for at least 1 h. VO2Fick and VO2Haldane were measured,
      respectively, with the standard formulae (using arterial and central venous
      saturation measured with a blood gas analyzer) and with a metabolic monitor.
      RESULTS: Forty-four paired measurements of VO2 were obtained. At each timepoint,
      the median (interquartile range, 25-75) VO2Haldane values were significantly
      higher than the median VO2Fick values (126 (103-192) vs. 90 (66-149) mL O2/min/m
      (P = 0.004) before FC and 129 (105-189) vs. 80 (54-119) mL O2/min/m (P = 0.001)
      after FC). Correlation between the DeltaVO2Fick and the DeltaVO2Haldane (%)
      measurements was poor, with an r = 0.06, (P = 0.77). The mean bias was 8.6%
      [limits of agreement (LOA): -75.7%, 92.9%]. CONCLUSIONS: Analysis of agreement
      showed poor concordance for the DeltaVO2Haldane and the DeltaVO2Fick (%) with a
      low mean bias but large and clinically unacceptable LOA. DeltaVO2Haldane and
      DeltaVO2Fick (%) are not interchangeable in these conditions.

PMID- 28452907
TI  - In a Mouse Model of Sepsis, Hepcidin Ablation Ameliorates Anemia More Effectively
      than Iron and Erythropoietin Treatment.
AB  - Intensive care unit (ICU) anemia is an extreme version of anemia of inflammation
      that occurs commonly in critically ill patients and is associated with increased
      morbidity and mortality. Currently available therapies for ICU anemia have shown
      inconsistent efficacies in clinical trials. We conducted a systematic study of
      the effects of early versus delayed iron (Fe) and/or erythropoietin (EPO) therapy
      in our previously characterized mouse model of ICU anemia based on an injection
      of heat-killed Brucella abortus. To study the effects of ongoing inflammation on
      the response to therapy, inflamed wild-type (WT) and hepcidin knockout (HKO) mice
      were treated at either early (days 1 and 2) or delayed (days 7 and 8) time points
      after the inflammatory stimulus. In the early treatment group, Fe and/or EPO
      therapy did not increase hemoglobin (Hgb) levels or reticulocyte production in
      either the inflamed WT or HKO groups. In the delayed treatment group, combination
      Fe + EPO therapy did increase Hgb and reticulocyte production in WT mice (mean
      DeltaHgb in WT saline group -9.2 g/dL vs. Fe/EPO -5.5 g/dL; P < 0.001). The HKO
      mice in the delayed treatment group did not improve their Hgb, but HKO mice in
      all treatment groups developed a milder anemia than the WT mice. Our findings
      indicate that combination Fe + EPO therapy is effective in partially reversing
      ICU anemia when administered after the phase of acute inflammation. Hepcidin
      ablation alone was more effective in attenuating ICU anemia than Fe + EPO
      therapy, which indicates the potential of antihepcidin therapeutics in treating
      ICU anemia.

PMID- 28452909
TI  - Exploring the Predictive Ability of Dysfunctional High-Density Lipoprotein for
      Adverse Outcomes in Emergency Department Patients with Sepsis: A Preliminary
      Investigation.
AB  - BACKGROUND: High density lipoprotein (HDL) can be readily oxidized in
      inflammatory conditions and exhibit pro-inflammatory and dysfunctional (Dys-HDL)
      characteristics. We hypothesize that Dys-HDL may predict adverse outcomes and
      correlate with inflammatory cytokines in sepsis. METHODS: Emergency department
      (ED) patients with sepsis were enrolled. Blood was drawn at enrollment and after
      48 h. Dys-HDL, expressed as HDL inflammatory index (HII), and cytokines were
      measured. Multivariable logistic regression was used to determine the predictive
      ability of Dys-HDL for adverse outcomes (death, discharge to hospice, or nursing
      home). RESULTS: Thirty-five patients were included in the study. HII was not
      significantly different at baseline or 48 h between patients with adverse
      outcomes versus those without. However, there was a significant difference in
      change in HII over the first 48 h between those with adverse outcomes (+0.21, 95%
      CI -0.13 to 0.31) versus those without (-0.11, 95% CI -1 to 0.11) (P = 0.025).
      Logistic regression revealed increasing HII to be an independent predictor of
      adverse outcomes (OR 5.2, 95% CI 1.1-25.1 P = 0.040). Of the 24 patents with
      cytokine measurements at both time points, significant inverse correlations
      between change in HII and change in GRO (rs = -0.52, P = 0.0088) and monocyte
      chemotactic protein-1 (rs = -0.61, P = 0.0014) concentrations over 48 h were
      observed. CONCLUSION: Increasing Dys-HDL concentrations in the first 48 h of
      sepsis are associated with an ongoing inflammatory response and adverse clinical
      outcomes. Early changes in HII may be a potential biomarker in ED patients
      admitted with sepsis.

PMID- 28452910
TI  - Brief Report: Safety of Frequent Blood Sampling in Research Participants in an
      Acute HIV Infection Cohort in Thailand.
AB  - INTRODUCTION: Anemia is a potential adverse effect of phlebotomy during
      participation in research. Clinical studies of acute HIV infection (AHI) require
      frequent phlebotomy to maximize scientific yield, but this participant population
      may also be at increased risk for anemia and other adverse events. OBJECTIVE: The
      objective of this study was to describe baseline and longitudinal hemoglobin
      changes among participants with AHI. METHODS: Participants with AHI (n = 202)
      were enrolled in a prospective cohort study in Thailand. AHI was diagnosed using
      pooled nucleic acid testing and sequential HIV antibody immunoassays.
      Antiretroviral therapy was initiated on enrollment. During 48 weeks of study
      participation, a total of 629 mL of blood was drawn over 14 visits. Hemoglobin
      levels were measured serially, and abnormalities were graded using the Division
      of AIDS (National Institute of Allergy and Infectious Diseases) adverse event
      table. RESULTS: AHI was diagnosed at a median of 18 days after infection. Mean
      hemoglobin at enrollment of male participants was 14.8 g/dL, and for females, it
      was 13.0 g/dL. Over 48 weeks, there was a mean increase of 0.2 g/dL among men (P
      = 0.01) and a decrease of 0.7 g/dL among women (P = 0.03). The overall prevalence
      of anemia was low, with 7 (3.5%) of 202 fulfilling grade 1 or 2 anemia criteria.
      CONCLUSIONS: Anemia was rare after frequent phlebotomy in research participants
      with AHI, before and after antiretroviral therapy. Given that the blood volume
      drawn from this study did not pose substantial clinical risk, increasing the
      volume of blood drawn for research purposes in acute HIV-infected research
      participants could be considered for future studies.

PMID- 28452911
TI  - The Effect of HIV-Centered Obstetric Care on Perinatal Outcomes Among a Cohort of
      Women Living With HIV.
AB  - BACKGROUND: Elimination of perinatal transmission is possible but limited by
      missed care opportunities. Our objective was to investigate the effects of HIV
      centered obstetric care (HCC) on missed care opportunities and perinatal HIV
      transmission in 2 obstetric cohorts at our institution from 2000 to 2014.
      METHODS: This was a retrospective cohort study of HIV-exposed mother-infant pairs
      delivering from 2000 to 2014, analyzed according to SQUIRE 2.0 (Standards for
      Quality Improvement Reporting Excellence) guidelines. Before 2009, women received
      care in high-risk obstetric care (HRC); subsequently, an HCC service was
      established. Women who received HRC vs HCC obstetric care were compared to
      determine differences in maternal and neonatal outcomes. Continuous variables
      were compared with Student t test and Wilcoxon rank sum tests. Categorical
      variables were compared using chi test and Fisher exact test. Logistic regression
      analyses were performed to determine factors associated with outcomes of
      interest. RESULTS: Over 14 years, 161 women delivered 217 HIV-exposed infants; 78
      (36%) women received HCC. Two perinatal HIV transmissions (1.5%) occurred in HRC
      group compared with none in the HCC group (P = 0.3). Women in HCC were more
      likely to have HIV RNA viral load <1000 copies per milliliter at delivery (12% vs
      26%, P = 0.02), have a contraception plan before delivery (93% vs 60%, P <
      0.001), return for postpartum evaluation (80% vs 63%, P = 0.01), and have
      undetectable HIV viral load postpartum (50 copies per milliliter vs 2067, P <
      0.0001). CONCLUSIONS: HCC can potentially reduce the risk of perinatal HIV
      transmission by improving maternal virologic control during pregnancy and
      postpartum and increasing postpartum contraceptive use.

PMID- 28452912
TI  - Effects of a Brief Team Training Program on Surgical Teams' Nontechnical Skills:
      An Interrupted Time-Series Study.
AB  - BACKGROUND: Up to 60% of adverse events in surgery are the result of poor
      communication and teamwork. Nontechnical skills in surgery (NOTSS) are critical
      to the success of surgery and patient safety. The study aim was to evaluate the
      effect of a brief team training intervention on teams' observed NOTSS. METHODS:
      Pretest-posttest interrupted time-series design with statistical process control
      analysis was used to detect longitudinal changes in teams' NOTSS. We evaluated
      NOTSS using the revised NOTECHS weekly for 20 to 25 weeks before and after
      implementation of a team training program. RESULTS: We observed 179 surgical
      procedures with cardiac, vascular, upper gastrointestinal, and hepatobiliary
      teams. Mean posttest NOTECHS scores increased across teams, showing special cause
      variation. There were also significant before and after improvements in NOTECHS
      scores in respect to professional role and in the use of the Surgical Safety
      Checklist. CONCLUSIONS: Our results suggest associated improvements in teams'
      NOTSS after implementation of the team training program.

PMID- 28452913
TI  - Improving Patient Safety in Handover From Intensive Care Unit to General Ward: A
      Systematic Review.
AB  - OBJECTIVES: Despite of the increasing knowledge about patient safety improvements
      in the handover process in hospitals, we still lack knowledge about what
      magnitude of patient safety gains can be expected from improvements in handover
      between the intensive care unit (ICU) and the general ward. The aim of this
      systematic review was to investigate which handover tools are devised and
      evaluated with the aim of improving patient safety in the handover process from
      ICU to ward and whether the described handover tools fulfill their purpose.
      METHODS: A systematic literature search of 6 databases was performed to answer
      the review question, developed by using the "Patient Population, Intervention,
      Comparison, Outcome" format. Two authors independently performed the selection
      process, as well as the data extraction and quality assessment. The
      recommendations of the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses Statement were followed. RESULTS: Eight studies were finally included in
      the qualitative analysis. One study investigated a written information tool, 1
      study investigated improved verbal information, 1 study investigated the effect
      of an additional safety check, and 5 studies investigated a Liaison Nurse as
      handover tool. Because of heterogeneity among the included studies, the study
      results could not be pooled. CONCLUSIONS: Not many well-conducted studies can
      shed light on this important topic. Giving patients and their families a
      supplementary written or verbal status report before transfer might improve
      patient safety. The introduction of a Liaison Nurse may be effective in improving
      communication between ICU and ward staff, which might reduce risks in patient
      safety. However, there is no evidence of improved mortality and/or readmission
      rates after introducing handover tools in the transfer from ICU to ward.

PMID- 28452914
TI  - Cost-Benefit Analysis of a Support Program for Nursing Staff.
AB  - OBJECTIVES: A peer-support program called Resilience In Stressful Events (RISE)
      was designed to help hospital staff cope with stressful patient-related events.
      The aim of this study was to evaluate the impact of the RISE program by
      conducting an economic evaluation of its cost benefit. METHODS: A Markov model
      with a 1-year time horizon was developed to compare the cost benefit with and
      without the RISE program from a provider (hospital) perspective. Nursing staff
      who used the RISE program between 2015 and 2016 at a 1000-bed, private hospital
      in the United States were included in the analysis. The cost of running the RISE
      program, nurse turnover, and nurse time off were modeled. Data on costs were
      obtained from literature review and hospital data. Probabilities of quitting or
      taking time off with or without the RISE program were estimated using survey
      data. Net monetary benefit (NMB) and budget impact of having the RISE program
      were computed to determine cost benefit to the hospital. RESULTS: Expected model
      results of the RISE program found a net monetary benefit savings of US $22,576.05
      per nurse who initiated a RISE call. These savings were determined to be 99.9%
      consistent on the basis of a probabilistic sensitivity analysis. The budget
      impact analysis revealed that a hospital could save US $1.81 million each year
      because of the RISE program. CONCLUSIONS: The RISE program resulted in
      substantial cost savings to the hospital. Hospitals should be encouraged by these
      findings to implement institution-wide support programs for medical staff, based
      on a high demand for this type of service and the potential for cost savings.

PMID- 28452915
TI  - Leapfrog Hospital Safety Score, Magnet Designation, and Healthcare-Associated
      Infections in United States Hospitals.
AB  - OBJECTIVE: Healthcare-associated infections (HAIs) pose a challenge to patient
      safety. Although studies have explored individual level, few have focused on
      organizational factors such as a hospital's safety infrastructure (indicated by
      Leapfrog Hospital Safety Score) or workplace quality (Magnet recognition). The
      aim of the study was to determine whether Magnet and hospitals with better
      Leapfrog Hospital Safety Scores have fewer HAIs. METHODS: Ordered probit
      regression analyses tested associations between Safety Score, Magnet status, and
      standardized infection ratios, depicting whether a hospital had a Clostridium
      difficile infection (CDI) and methicillin-resistant Staphylococcus aureus (MRSA)
      bloodstream infection standardized infection ratio that was "better," "no
      different," or "worse" than a National Benchmark as per Centers for Disease
      Control and Prevention's National Healthcare Safety Network definitions. RESULTS:
      Accounting for confounders, relative to "A" hospitals, "B" and "C" hospitals had
      significant and negative relationships with CDI (-0.16, P < 0.01, and -0.14, P <
      0.05, respectively) but not MRSA bacteremia. Magnet hospitals had a significant
      and positive relationship with MRSA bloodstream infections (0.74, P < 0.001) but
      a significant negative relationship with CDI (-0.21, P < 0.01) compared with non
      Magnet. CONCLUSIONS: A hospitals performed better on CDI but not MRSA bloodstream
      infections. In contrast, Magnet designation was associated with fewer than
      expected MRSA infections but more than expected CDIs. These mixed results
      indicate that hospital global assessments of safety and workplace quality
      differentially and imperfectly predict its level of HAIs, suggesting the need for
      more precise organizational measures of safety and more nuanced approaches to
      infection prevention and reduction.

PMID- 28452916
TI  - Never Events in UK General Practice: A Survey of the Views of General
      Practitioners on Their Frequency and Acceptability as a Safety Improvement
      Approach.
AB  - BACKGROUND: Never events (NEs) are serious preventable patient safety incidents
      and are a component of formal quality and safety improvement (Q&SI) policies in
      the United Kingdom and elsewhere. A preliminary list of NEs for UK general
      practice has been developed, but the frequency of these events, or their
      acceptability to general practitioner (GPs) as a Q&SI approach, is currently
      unknown. The study aims to estimate (1) the frequency of 10 NEs occurring within
      GPs' own practices and (2) the extent to which the NE approach is perceived as
      acceptable for use. METHODS: General practitioners were surveyed, and mixed
      effects logistic regression models examined the relationship between GP opinions
      of NE, estimates of NE frequency, and the characteristics of the GPs and their
      practices. RESULTS: Responses from 556 GPs in 412 practices were analyzed. Most
      participants (70%-88%, depending on the NE) agreed that the described incident
      should be designated as a NE. Three NEs were estimated to have occurred in less
      than 4% of practices in the last year; however, two NEs were estimated to have
      occurred in 45% to 61% of the practices. General practitioners reporting that a
      NE had occurred in their practice in the last year were significantly less likely
      to agree with the designation as a NE compared with GPs not reporting a NE (odds
      ratio, 0.42; 95% CI = 0.36-0.49). CONCLUSIONS: The NE approach may have Q&SI
      potential for general practice, but further work to adapt the concept and content
      is required.This is an open access article distributed under the Creative Commons
      Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
      reproduction in any medium, provided the original work is properly cited.

PMID- 28452917
TI  - Quality of Handoffs in Community Pharmacies.
AB  - OBJECTIVES: The aims of the study were to characterize handoffs in community
      pharmacies and to examine factors that contribute to perceived handoff quality.
      METHODS: A cross-sectional study of community pharmacists in a Midwest State of
      the United States. Self-administered questionnaires were used to collect
      information on participant and practice setting characteristics. Data were
      analyzed using descriptive statistics and multivariate logistic regression.
      RESULTS: A total of 445 completed surveys were returned (response rate, 82%). In
      almost half of the time, handoffs that occur in a community pharmacy setting were
      inaccurate or incomplete. Nearly half of the time handoffs occur in environments
      full of interruptions and distractions. More than 90% of the respondents
      indicated that they have undergone no formal training on proper ways of handing
      off information. Nearly 40% of respondents reported that their pharmacy
      dispensing technology does not have adequate functionality to support handing off
      information and that at least 50% of the time, poor handoffs result in additional
      work to the pharmacist because of the need for complete information before
      providing patient care. Multivariate analysis showed that being very familiar
      with patients, lower daily prescription volume, not having a 24-hour operation,
      and larger percentage of handoffs occurring in a synchronous fashion are all
      associated with better handoff quality. CONCLUSIONS: Handoffs occur frequently
      and are problematic in community pharmacies. Current pharmacy environments offer
      limited support to conduct good handoffs, and as a result, pharmacists report
      loss of information. This could present as a significant patient safety hazard.
      Future interventions should target facilitating better communication during shift
      changes.

PMID- 28452918
TI  - Detecting Medication Administration Errors.

PMID- 28452919
TI  - Response to: Reproducibility of 24-h ambulatory blood pressure and measures of
      autonomic function: methodological and statistical issue.

PMID- 28452920
TI  - High Tacrolimus Clearance Is a Risk Factor for Acute Rejection in the Early Phase
      After Renal Transplantation.
AB  - BACKGROUND: Patients with high tacrolimus clearance eliminate more drug within a
      dose interval compared with those with low clearance. Delays in dosing time will
      result in transient periods of lower concentrations in high versus low clearance
      patients. Transient subtherapeutic tacrolimus concentrations may induce acute
      rejection episodes. METHODS: A retrospective study in all renal transplant
      patients treated with tacrolimus at our center from 2009 to 2013 was conducted.
      The association between individually estimated tacrolimus clearance (daily
      tacrolimus dose [mg]/trough concentration [MUg/L]) and biopsy-proven acute
      rejection (BPAR) the first 90 days posttransplantation was investigated. RESULTS:
      In total, 638 patients treated with oral tacrolimus were included in the
      analysis. Eighty-five (13.3%) patients experienced BPAR. Patients were stratified
      into 4 groups per their estimated clearance. The patients in the high clearance
      group had significantly higher incidence of BPAR (20.6%) with a hazard ratio of
      2.39 (95% confidence interval, 1.30-4.40) compared with the low clearance group.
      Clearance estimate (as a continuous variable) showed a hazard ratio of 2.25 (95%
      confidence interval, 1.70-2.99) after adjusting for other risk factors. There
      were no significant differences in neither trough concentrations the first week
      after transplantation nor time to target trough concentration between patients
      later experiencing BPAR or not. CONCLUSIONS: High estimated clearance is
      significantly associated with increased risk of BPAR the first 90 days
      posttransplantation and may predict an increased risk of rejection in the early
      phase after renal transplantation.

PMID- 28452921
TI  - Targeting Circulating Leukocytes and Pyroptosis During Ex Vivo Lung Perfusion
      Improves Lung Preservation.
AB  - BACKGROUND: The role of the circulating leukocytes in lungs and their
      relationship with circulating proinflammatory cytokines during ischemia
      reperfusion injury is not well understood. Using ex vivo lung perfusion (EVLP) to
      investigate the pathophysiology of isolated lungs, we aimed to identify a
      therapeutic target to optimize lung preservation leading to successful lung
      transplantation. METHODS: Rat heart-lung blocks were placed on EVLP for 4 hours
      with or without a leukocyte-depleting filter (LF). After EVLP, lung grafts were
      transplanted, and posttransplant outcomes were compared. RESULTS: Lung function
      was significantly better in lung grafts on EVLP with a LF than in lungs on EVLP
      without a LF. The interleukin (IL)-6 levels in the lung grafts and EVLP perfusate
      were also significantly lower after EVLP with a LF. Interestingly, IL-6 levels in
      the perfusate did not increase after the lungs were removed from the EVLP
      circuit, indicating that the cells trapped by the LF were not secreting IL-6. The
      trapped cells were analyzed with flow cytometry to detect apoptosis and
      pyroptosis; 26% were pyroptotic (Caspase-1-positive). After transplantation,
      there was better graft function and less inflammatory response if a LF was used
      or a caspase-1 inhibitor was administered during EVLP. CONCLUSIONS: Our data
      demonstrated that circulating leukocytes derived from donor lungs, and not
      circulating proinflammatory cytokines substantially impaired the quality of lung
      grafts through caspase-1-induced pyroptotic cell death during EVLP. Removing
      these cells with a LF and/or inhibiting pyroptosis of the cells can be a new
      therapeutic approach leading to long-term success after lung transplantation.

PMID- 28452922
TI  - Chronic AMR in Liver Transplant: Validation of the 1-Year cAMR Score's Ability to
      Determine Long-term Outcome.
AB  - BACKGROUND: A proposed chronic antibody-mediated rejection (AMR) score has
      recently predicted 50%10-year death-censored allograft loss in patients with
      donor-specific alloantibodies (DSA) mean florescence intensity (MFI) greater than
      10 000 and requires confirmation in patients with lower MFI (1000-10 000).
      METHODS: All patients who underwent liver transplantation from January 2000 to
      April 2009, had DSA (MFI >=1000) in serum 10 to 14 months postliver
      transplantation, and had a protocolized liver biopsy were evaluated (n = 230).
      The previously proposed chronic AMR (cAMR) score was used to risk-stratify
      putative chronic AMR in DSA+ patients with MFI from 1000 to 10 000. RESULTS: The
      MFI distribution of DSA+ recipients were as follows: 66% had MFI 1000 to 4999,
      14% had MFI 5000 to 10 000, and 20% had MFI greater than 10 000. The cAMR score
      distribution on 1-year protocol liver biopsy found that 41% had a score less than
      13; 27% a score of 13 to 27.5, and 32% a score greater than 27.5. MFI correlated
      with 1-year cAMR category (<13, 46% vs 21% and >27.5, 29% vs 42% when MFI was
      1000-10 000 vs MFI >10 000; P = 0.047). In patients with a cAMR score less than
      13, 10-year death-censored allograft survival was 96% to 100% regardless of MFI
      (P = NS). The risk of allograft loss increased in patients with a cAMR score
      greater than 13 (P = 0.004) in DSA+ patients with MFI 1000 to 10 000. DSA MFI
      greater than 10 000 versus MFI 1000 to 10 000 at 1 year was also more likely to
      persist at 5 years (95% vs 68%; P < 0.0001). CONCLUSIONS: Validation of the
      previously proposed cAMR score in a separate cohort predicts death-censored long
      term allograft failure in DSA+ patients regardless of MFI, and higher MFI at 1
      year predicts DSA persistence at 5 years.

PMID- 28452925
TI  - Distributed Fault Detection Based on Credibility and Cooperation for WSNs in
      Smart Grids.
AB  - Due to the increasingly important role in monitoring and data collection that
      sensors play, accurate and timely fault detection is a key issue for wireless
      sensor networks (WSNs) in smart grids. This paper presents a novel distributed
      fault detection mechanism for WSNs based on credibility and cooperation. Firstly,
      a reasonable credibility model of a sensor is established to identify any
      suspicious status of the sensor according to its own temporal data correlation.
      Based on the credibility model, the suspicious sensor is then chosen to launch
      fault diagnosis requests. Secondly, the sending time of fault diagnosis request
      is discussed to avoid the transmission overhead brought about by unnecessary
      diagnosis requests and improve the efficiency of fault detection based on
      neighbor cooperation. The diagnosis reply of a neighbor sensor is analyzed
      according to its own status. Finally, to further improve the accuracy of fault
      detection, the diagnosis results of neighbors are divided into several
      classifications to judge the fault status of the sensors which launch the fault
      diagnosis requests. Simulation results show that this novel mechanism can achieve
      high fault detection ratio with a small number of fault diagnoses and low data
      congestion probability.

PMID- 28452924
TI  - Genome-Wide Analyses of MicroRNA Profiling in Interleukin-27 Treated Monocyte
      Derived Human Dendritic Cells Using Deep Sequencing: A Pilot Study.
AB  - MicroRNAs (miRNAs) regulate gene expression and thereby influence cell fate and
      function. Recent studies suggest that an abundant class of miRNAs play important
      roles in immune cells, such as T cells, natural killer (NK) cells, B cells, and
      dendritic cells (DCs). Interleukin (IL)-27 is a member of the IL-12 family of
      cytokines with broad anti-viral effects. It is a potent inhibitor of HIV-1
      infection in CD4+ T cells and macrophages, as well as monocyte-derived immature
      dendritic cells (iDCs). This pilot study compared miRNA profiles between iDCs and
      IL-27-treated iDCs (27DCs) using deep sequencing methods and identified 46 known
      miRNAs that were significantly differentially expressed in 27DCs: 36 were
      upregulated and 10 downregulated by IL-27. Many of the potential target genes of
      these miRNAs are involved in IL-27 associated pathways, such as JAK/STAT, MAPKs,
      and PI3K and several were also previously reported to be involved in the
      regulation of human DC function. This study found that these miRNAs also
      potentially target several viral genomes and therefore may have antiviral
      effects. Four of these differential miRNAs (miR-99a-5p, miR-222-3p, miR-138-5p,
      and miR-125b-5p) were validated using quantitative reverse transcription PCR (RT
      qPCR). Twenty-two novel miRNAs were discovered from deep sequencing and confirmed
      using RT-qPCR. This study furthers the understanding of the role of IL-27 in
      immunity and lays a foundation for future characterization of the role of
      specific miRNAs in DCs.

PMID- 28452926
TI  - KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 Mutations in Pancreatic Cancer.
AB  - Pancreatic cancer is a disease that has a very high fatality rate and one of the
      highest mortality ratios among all major cancers, remaining the fourth leading
      cause of cancer-related deaths in developed countries. The major treatment of
      pancreatic cancer is surgery; however, only 15-20% of patients are candidates for
      it at the diagnosis of disease. On the other hand, survival in patients, who
      undergo surgery, is less than 30%. In most cancers, genome stability is disturbed
      and pancreatic cancer is not the exception. Approximately 97% of pancreatic
      cancers have gene derangements, defined by point mutations, amplifications,
      deletions, translocations, and inversions. This review describes the most
      frequent genetic alterations found in pancreatic cancer.

PMID- 28452927
TI  - The "Metabolic Memory" Theory and the Early Treatment of Hyperglycemia in
      Prevention of Diabetic Complications.
AB  - Several epidemiological and prospective studies suggest that an early intensive
      control of hyperglycaemia is able to decrease the risk of diabetic micro- and
      macro-vascular complications. A growing body of experimental evidence supports
      the concept that the risk for diabetes complications may be linked to oxidative
      stress, non-enzymatic glycation of proteins, epigenetic changes, and chronic
      inflammation, laying the foundation for the "metabolic memory" theory. From a
      clinical point of view, this theory supports the need for a very early aggressive
      treatment, with the goal of normalizing metabolic control as soon as possible. It
      may also prove beneficial to introduce therapeutic agents that are able to reduce
      reactive species and glycation, in addition to presenting better control of
      glucose levels in patients with diabetes, in order to minimize long-term diabetes
      complications. In this review, we evaluate the effect of glucose intake and
      metabolism in the light of this theory.

PMID- 28452929
TI  - Chemiresistor Devices for Chemical Warfare Agent Detection Based on Polymer
      Wrapped Single-Walled Carbon Nanotubes.
AB  - Chemical warfare agents (CWA) continue to present a threat to civilian
      populations and military personnel in operational areas all over the world.
      Reliable measurements of CWAs are critical to contamination detection, avoidance,
      and remediation. The current deployed systems in United States and foreign
      militaries, as well as those in the private sector offer accurate detection of
      CWAs, but are still limited by size, portability and fabrication cost. Herein, we
      report a chemiresistive CWA sensor using single-walled carbon nanotubes (SWCNTs)
      wrapped with poly(3,4-ethylenedioxythiophene) (PEDOT) derivatives. We demonstrate
      that a pendant hexafluoroisopropanol group on the polymer that enhances
      sensitivity to a nerve agent mimic, dimethyl methylphosphonate, in both nitrogen
      and air environments to concentrations as low as 5 ppm and 11 ppm, respectively.
      Additionally, these PEDOT/SWCNT derivative sensor systems experience negligible
      device performance over the course of two weeks under ambient conditions.

PMID- 28452928
TI  - Near Infrared Fluorescence Imaging in Nano-Therapeutics and Photo-Thermal
      Evaluation.
AB  - The unresolved and paramount challenge in bio-imaging and targeted therapy is to
      clearly define and demarcate the physical margins of tumor tissue. The ability to
      outline the healthy vital tissues to be carefully navigated with transection
      while an intraoperative surgery procedure is performed sets up a necessary and
      under-researched goal. To achieve the aforementioned objectives, there is a need
      to optimize design considerations in order to not only obtain an effective
      imaging agent but to also achieve attributes like favorable water solubility,
      biocompatibility, high molecular brightness, and a tissue specific targeting
      approach. The emergence of near infra-red fluorescence (NIRF) light for tissue
      scale imaging owes to the provision of highly specific images of the target
      organ. The special characteristics of near infra-red window such as minimal auto
      fluorescence, low light scattering, and absorption of biomolecules in tissue
      converge to form an attractive modality for cancer imaging. Imparting molecular
      fluorescence as an exogenous contrast agent is the most beneficial attribute of
      NIRF light as a clinical imaging technology. Additionally, many such agents also
      display therapeutic potentials as photo-thermal agents, thus meeting the dual
      purpose of imaging and therapy. Here, we primarily discuss molecular imaging and
      therapeutic potentials of two such classes of materials, i.e., inorganic NIR dyes
      and metallic gold nanoparticle based materials.

PMID- 28452931
TI  - An Adaptive B-Spline Neural Network and Its Application in Terminal Sliding Mode
      Control for a Mobile Satcom Antenna Inertially Stabilized Platform.
AB  - The mobile satcom antenna (MSA) enables a moving vehicle to communicate with a
      geostationary Earth orbit satellite. To realize continuous communication, the MSA
      should be aligned with the satellite in both sight and polarization all the time.
      Because of coupling effects, unknown disturbances, sensor noises and unmodeled
      dynamics existing in the system, the control system should have a strong
      adaptability. The significant features of terminal sliding mode control method
      are robustness and finite time convergence, but the robustness is related to the
      large switching control gain which is determined by uncertain issues and can lead
      to chattering phenomena. Neural networks can reduce the chattering and
      approximate nonlinear issues. In this work, a novel B-spline curve-based B-spline
      neural network (BSNN) is developed. The improved BSNN has the capability of shape
      changing and self-adaption. In addition, the output of the proposed BSNN is
      applied to approximate the nonlinear function in the system. The results of
      simulations and experiments are also compared with those of PID method, non
      singularity fast terminal sliding mode (NFTSM) control and radial basis function
      (RBF) neural network-based NFTSM. It is shown that the proposed method has the
      best performance, with reliable control precision.

PMID- 28452930
TI  - Interplay between the Hepatitis B Virus and Innate Immunity: From an
      Understanding to the Development of Therapeutic Concepts.
AB  - The hepatitis B virus (HBV) infects hepatocytes, which are the main cell type
      composing a human liver. However, the liver is enriched with immune cells,
      particularly innate cells (e.g., myeloid cells, natural killer and natural killer
      T-cells (NK/NKT), dendritic cells (DCs)), in resting condition. Hence, the study
      of the interaction between HBV and innate immune cells is instrumental to: (1)
      better understand the conditions of establishment and maintenance of HBV
      infections in this secondary lymphoid organ; (2) define the role of these innate
      immune cells in treatment failure and pathogenesis; and (3) design novel immune
      therapeutic concepts based on the activation/restoration of innate cell functions
      and/or innate effectors. This review will summarize and discuss the current
      knowledge we have on this interplay between HBV and liver innate immunity.

PMID- 28452932
TI  - Eating Like a Rainbow: The Development of a Visual Aid for Nutritional Treatment
      of CKD Patients. A South African Project.
AB  - Providing nutritional education for chronic kidney disease (CKD) patients in
      South Africa is complicated by several conditions: the population is composed of
      diverse ethnic groups, each with its own culture and food preferences; eleven
      languages are spoken and illiteracy is common in the lower socio-economic groups.
      Food preparation and storage are affected by the lack of electricity and
      refrigeration, and this contributes to a monotonous diet. In traditional African
      culture, two meals per day are often shared "from the pot", making portion
      control difficult. There is both under- and over-nutrition; late referral of CKD
      is common. Good quality protein intake is often insufficient and there are
      several misconceptions about protein sources. There is a low intake of vegetables
      and fruit, while daily sodium intake is high, averaging 10 g/day, mostly from
      discretionary sources. On this background, we would like to describe the
      development of a simplified, visual approach to the "renal diet", principally
      addressed to illiterate/non-English speaking CKD patients in Southern Africa,
      using illustrations to replace writing. This tool "Five steps to improve renal
      diet compliance", also called "Eating like a Rainbow", was developed to try to
      increase patients' understanding, and has so far only been informally validated
      by feedback from users. The interest of this study is based on underlining the
      feasibility of dietary education even in difficult populations, focusing
      attention on this fundamental issue of CKD care in particular in countries with
      limited access to chronic dialysis.

PMID- 28452933
TI  - Performance Analysis of Global Navigation Satellite System Signal Acquisition
      Aided by Different Grade Inertial Navigation System under Highly Dynamic
      Conditions.
AB  - Under the high dynamic conditions, Global Navigation Satellite System (GNSS)
      signals produce great Doppler frequency shifts, which hinders the fast
      acquisition of signals. Inertial Navigation System (INS)-aided acquisition can
      improve the acquisition performance, whereas the accuracy of Doppler shift and
      code phase estimation are mainly determined by the INS precision. The relation
      between the INS accuracy and Doppler shift estimation error has been derived,
      while the relation between the INS accuracy and code phase estimation error has
      not been deduced. In this paper, in order to theoretically analyze the effects of
      INS errors on the performance of Doppler shift and code phase estimations, the
      connections between them are re-deduced. Moreover, the curves of the
      corresponding relations are given for the first time. Then, in order to have a
      better verification of the INS-aided acquisition, a high dynamic scenario is
      designed. Furthermore, by using the deduced mathematical relation, the effects of
      different grade INS on the GNSS (including Global Positioning System (GPS) and
      BeiDou Navigation Satellite System (BDS)) signal acquisition are analyzed.
      Experimental results demonstrate that the INS-aided acquisition can reduce the
      search range of local frequency and code phase, and achieve fast acquisition.
      According to the experimental results, a suitable INS can be chosen for the
      deeply coupled integration.

PMID- 28452934
TI  - A Genetic Algorithm for the Generation of Packetization Masks for Robust Image
      Communication.
AB  - Image interleaving has proven to be an effective solution to provide the
      robustness of image communication systems when resource limitations make reliable
      protocols unsuitable (e.g., in wireless camera sensor networks); however, the
      search for optimal interleaving patterns is scarcely tackled in the literature.
      In 2008, Rombaut et al. presented an interesting approach introducing a
      packetization mask generator based in Simulated Annealing (SA), including a cost
      function, which allows assessing the suitability of a packetization pattern,
      avoiding extensive simulations. In this work, we present a complementary study
      about the non-trivial problem of generating optimal packetization patterns. We
      propose a genetic algorithm, as an alternative to the cited work, adopting the
      mentioned cost function, then comparing it to the SA approach and a torus
      automorphism interleaver. In addition, we engage the validation of the cost
      function and provide results attempting to conclude about its implication in the
      quality of reconstructed images. Several scenarios based on visual sensor
      networks applications were tested in a computer application. Results in terms of
      the selected cost function and image quality metric PSNR show that our algorithm
      presents similar results to the other approaches. Finally, we discuss the
      obtained results and comment about open research challenges.

PMID- 28452935
TI  - The Stearoyl-CoA Desaturase-1 (Desat1) in Drosophila cooperated with Myc to
      Induce Autophagy and Growth, a Potential New Link to Tumor Survival.
AB  - Lipids are an important energy supply in our cells and can be stored or used to
      produce macromolecules during lipogenesis when cells experience nutrient
      starvation. Our proteomic analysis reveals that the Drosophila homologue of human
      Stearoyl-CoA desaturase-1 Desat1) is an indirect target of Myc in fat cells.
      Stearoyl-CoA desaturases are key enzymes in the synthesis of monounsaturated
      fatty acids critical for the formation of complex lipids such as triglycerides
      and phospholipids. Their function is fundamental for cellular physiology, however
      in tumors, overexpression of SCD-1 and SCD-5 has been found frequently associated
      with a poor prognosis. Another gene that is often upregulated in tumors is the
      proto-oncogene c-myc, where its overexpression or increased protein stability,
      favor cellular growth. Here, we report a potential link between Myc and Desat1 to
      control autophagy and growth. Using Drosophila, we found that expression of
      Desat1, in metabolic tissues like the fat body, in the gut and in epithelial
      cells, is necessary for Myc function to induce autophagy a cell eating mechanism
      important for energy production. In addition, we observed that reduction of
      Desat1 affects Myc ability to induce growth in epithelial cells. Our data also
      identify, in prostatic tumor cells, a significant correlation between  the
      expression of Myc and SCD-1 proteins, suggesting the existence of a potential
      functional relationship between the activities of these proteins in sustaining
      tumor progression.

PMID- 28452936
TI  - A Novel MEMS Gyro North Finder Design Based on the Rotation Modulation Technique.
AB  - Gyro north finders have been widely used in maneuvering weapon orientation, oil
      drilling and other areas. This paper proposes a novel Micro-Electro-Mechanical
      System (MEMS) gyroscope north finder based on the rotation modulation (RM)
      technique. Two rotation modulation modes (static and dynamic modulation) are
      applied. Compared to the traditional gyro north finders, only one single MEMS
      gyroscope and one MEMS accelerometer are needed, reducing the total cost since
      high-precision gyroscopes and accelerometers are the most expensive components in
      gyro north finders. To reduce the volume and enhance the reliability, wireless
      power and wireless data transmission technique are introduced into the rotation
      modulation system for the first time. To enhance the system robustness, the
      robust least square method (RLSM) and robust Kalman filter (RKF) are applied in
      the static and dynamic north finding methods, respectively. Experimental
      characterization resulted in a static accuracy of 0.66 degrees  and a dynamic
      repeatability accuracy of 1 degrees , respectively, confirming the excellent
      potential of the novel north finding system. The proposed single gyro and single
      accelerometer north finding scheme is universal, and can be an important
      reference to both scientific research and industrial applications.

PMID- 28452937
TI  - An Authentication Protocol for Future Sensor Networks.
AB  - Authentication is one of the essential security services in Wireless Sensor
      Networks (WSNs) for ensuring secure data sessions. Sensor node authentication
      ensures the confidentiality and validity of data collected by the sensor node,
      whereas user authentication guarantees that only legitimate users can access the
      sensor data. In a mobile WSN, sensor and user nodes move across the network and
      exchange data with multiple nodes, thus experiencing the authentication process
      multiple times. The integration of WSNs with Internet of Things (IoT) brings
      forth a new kind of WSN architecture along with stricter security requirements;
      for instance, a sensor node or a user node may need to establish multiple
      concurrent secure data sessions. With concurrent data sessions, the frequency of
      the re-authentication process increases in proportion to the number of concurrent
      connections. Moreover, to establish multiple data sessions, it is essential that
      a protocol participant have the capability of running multiple instances of the
      protocol run, which makes the security issue even more challenging. The currently
      available authentication protocols were designed for the autonomous WSN and do
      not account for the above requirements. Hence, ensuring a lightweight and
      efficient authentication protocol has become more crucial. In this paper, we
      present a novel, lightweight and efficient key exchange and authentication
      protocol suite called the Secure Mobile Sensor Network (SMSN) Authentication
      Protocol. In the SMSN a mobile node goes through an initial authentication
      procedure and receives a re-authentication ticket from the base station. Later a
      mobile node can use this re-authentication ticket when establishing multiple data
      exchange sessions and/or when moving across the network. This scheme reduces the
      communication and computational complexity of the authentication process. We
      proved the strength of our protocol with rigorous security analysis (including
      formal analysis using the BAN-logic) and simulated the SMSN and previously
      proposed schemes in an automated protocol verifier tool. Finally, we compared the
      computational complexity and communication cost against well-known authentication
      protocols.

PMID- 28452938
TI  - Estrogen Modulates Specific Life and Death Signals Induced by LH and hCG in Human
      Primary Granulosa Cells In Vitro.
AB  - Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are glycoprotein
      hormones used for assisted reproduction acting on the same receptor (LHCGR) and
      mediating different intracellular signaling. We evaluated the pro- and anti
      apoptotic effect of 100 pM LH or hCG, in the presence or in the absence of 200
      pg/mL 17beta-estradiol, in long-term, serum-starved human primary granulosa cells
      (hGLC) and a transfected granulosa cell line overexpressing LHCGR (hGL5/LHCGR).
      To this purpose, phospho-extracellular-regulated kinase 1/2 (pERK1/2), protein
      kinase B (pAKT), cAMP-responsive element binding protein (pCREB) activation and
      procaspase 3 cleavage were evaluated over three days by Western blotting, along
      with the expression of target genes by real-time PCR and cell viability by
      colorimetric assay. We found that LH induced predominant pERK1/2 and pAKT
      activation STARD1, CCND2 and anti-apoptotic XIAP gene expression, while hCG
      mediated more potent CREB phosphorylation, expression of CYP19A1 and procaspase 3
      cleavage than LH. Cell treatment by LH is accompanied by increased (serum
      starved) cell viability, while hCG decreased the number of viable cells. The hCG
      specific, pro-apoptotic effect was blocked by a physiological dose of 17beta
      estradiol, resulting in pAKT activation, lack of procaspase 3 cleavage and
      increased cell viability. These results confirm that relatively high levels of
      steroidogenic pathway activation are linked to pro-apoptotic signals in vitro,
      which may be counteracted by other factors, i.e., estrogens.

PMID- 28452940
TI  - Does Unstable Employment Have an Association with Suicide Rates among the Young?
AB  - Although a growing body of literature has indicated that unemployment has a
      positive association with suicide, the dynamic aspects of unstable employment
      have not yet been considered in suicidology. This study explored the association
      between employment stability and completed suicide among people aged 25-34 years
      in 20 OECD (Organization for Economic Cooperation and Development) countries with
      time-series data (1994-2010). In order to consider the different aspects of
      unstable employment, we tested the impacts of employment protection legislation
      indicators as another proxy of job insecurity (employed, but unstable) apart from
      unemployment rates. Covariates, including economic growth rates, GDP per capita,
      fertility rates, and divorce rate, were controlled for. The analysis was designed
      to be gender- and age-specific, where observations with ages of 25-29 were
      separated from those with ages of 30-34. Random effect models were applied to
      examine changes over time in suicide rates, and other models were presented to
      check robustness. The results showed that it is a low level of employment
      protection, rather than unemployment itself, that was associated with increased
      suicide rates among all of the studied populations. The magnitude of the effect
      differed by gender.

PMID- 28452939
TI  - A Review: Proteomics in Retinal Artery Occlusion, Retinal Vein Occlusion,
      Diabetic Retinopathy and Acquired Macular Disorders.
AB  - Retinal artery occlusion (RAO), retinal vein occlusion (RVO), diabetic
      retinopathy (DR) and age-related macular degeneration (AMD) are frequent ocular
      diseases with potentially sight-threatening outcomes. In the present review we
      discuss major findings of proteomic studies of RAO, RVO, DR and AMD, including an
      overview of ocular proteome changes associated with anti-vascular endothelial
      growth factor (VEGF) treatments. Despite the severe outcomes of RAO, the proteome
      of the disease remains largely unstudied. There is also limited knowledge about
      the proteome of RVO, but proteomic studies suggest that RVO is associated with
      remodeling of the extracellular matrix and adhesion processes. Proteomic studies
      of DR have resulted in the identification of potential therapeutic targets such
      as carbonic anhydrase-I. Proliferative diabetic retinopathy is the most
      intensively studied stage of DR. Proteomic studies have established VEGF, pigment
      epithelium-derived factor (PEDF) and complement components as key factors
      associated with AMD. The aim of this review is to highlight the major milestones
      in proteomics in RAO, RVO, DR and AMD. Through large-scale protein analyses,
      proteomics is bringing new important insights into these complex pathological
      conditions.

PMID- 28452941
TI  - Failure to CAPTCHA Attention: Null Results from an Honesty Priming Experiment in
      Guatemala.
AB  - We report results from a large online randomised tax experiment in Guatemala. The
      trial involves short messages and choices presented to taxpayers as part of a
      CAPTCHA pop-up window immediately before they file a tax return, with the aim of
      priming honest declarations. In total our sample includes 627,242 taxpayers and
      3,232,430 tax declarations made over four months. Treatments include: honesty
      declaration; information about public goods; information about penalties for
      dishonesty, questions allowing a taxpayer to choose which public good they think
      tax money should be spent on; or questions allowing a taxpayer to state a view on
      the penalty for not declaring honestly. We find no impact of any of these
      treatments on the average amount of tax declared. We discuss potential causes for
      this null effect and implications for 'online nudges' around honesty priming.

PMID- 28452942
TI  - A Double Rate Localization Algorithm with One Anchor for Multi-Hop Underwater
      Acoustic Networks.
AB  - Localization is a basic issue for underwater acoustic networks (UANs). Currently,
      most localization algorithms only perform well in one-hop networks or need more
      anchors which are not suitable for the underwater environment. In this paper, we
      proposed a double rate localization algorithm with one anchor for multi-hop
      underwater acoustic networks (DRL). The algorithm firstly presents a double rate
      scheme which separates the localization procedure into two modes to increase the
      ranging accuracy in multi-hop UANs while maintaining the transmission rate. Then
      an optimal selection scheme of reference nodes was proposed to reduce the
      influence of references' topology on localization performance. The proposed DRL
      algorithm can be used in the multi-hop UANs to increase the localization accuracy
      and reduce the usage of anchor nodes. The simulation and experimental results
      demonstrated that the proposed DRL algorithm has a better localization
      performance than the previous algorithms in many aspects such as accuracy and
      communication cost, and is more suitable to the underwater environment.

PMID- 28452943
TI  - Pectic Bee Pollen Polysaccharide from Rosa rugosa Alleviates Diet-Induced Hepatic
      Steatosis and Insulin Resistance via Induction of AMPK/mTOR-Mediated Autophagy.
AB  - Despite it is used as a nutraceutical against diabetes and obesity, the mechanism
      of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP
      P) was isolated from Rosa rugosa, and its structure was characterized by 13C-NMR
      and Fourier transform-infrared spectroscopy (FT-IR). Using high glucose and fatty
      acids-treated HepG2 cells and high fat diet (HFD)-induced obesity mice, we
      detected its effect on insulin function and lipid metabolism based on autophagy.
      RBPP-P contained arabinogalactan, rhamnogalacturonan I, and homogalacturonan
      domains. In vivo studies demonstrated that RBPP-P markedly ameliorated insulin
      resistance, glucose intolerance, and liver steatosis in obese mice. The
      suppressive effects of RBPP-P on liver steatosis and triglyceride content were
      mediated by increased autophagy and lipase expression in liver. In AMPK knockdown
      cells (prkaa 1/2-/- MEF) and HFD-fed mice tissues (liver, gonadal white adipose,
      and inguinal white adipose), RBPP-P enhanced autophagy in AMPK/mTOR-dependent way
      in liver, but not in adipose tissue. These findings demonstrated that bee pollen
      polysaccharide alleviated liver steatosis and insulin resistance by promoting
      autophagy via an AMPK/mTOR-mediated signaling pathway, suggesting that RBPP-P
      could be a novel therapeutic agent used for the treatment of obesity and
      diabetes.

PMID- 28452944
TI  - Green Synthesis of Ag/Ag2O Nanoparticles Using Aqueous Leaf Extract of Eupatorium
      odoratum and Its Antimicrobial and Mosquito Larvicidal Activities.
AB  - The health challenges associated with pathogens and ectoparasites highlight the
      need for effective control approaches. Metal nanoparticles have been proposed as
      highly effective tools towards combatting different microbial organisms and
      parasites. The present work reports the antimicrobial and larvicidal potential of
      biosynthesized Ag/Ag2O nanoparticles using aqueous leaf extract of Eupatorium
      odoratum (EO). The constituents of the leaf extract act as both reducing and
      stabilizing agents. The UV-VIS spectra of the nanoparticles showed surface
      plasmon resonance. The particle size and shape of the nanoparticles was analysed
      by transmission electron microscopy (TEM). The larvicidal study was carried out
      using third and fourth instar Culex quinquefasciatus larvae. The mosquito larvae
      were exposed to varying concentrations of plant extract (EO) and the synthesized
      nanoparticles, and their percentage of mortality was accounted for at different
      time intervals of 12 h and 24 h periods of exposure. The nanoparticles were more
      lethal against third and fourth instars of Culex quinquefasciatus larvae at the
      24 h period of exposure with lower lethal concentration values (LC50 = 95.9 ppm;
      LC90 = 337.5 ppm) and (LC50 = 166.4 ppm; LC90 = 438.7 ppm) compared to the plant
      extract (LC50 = 396.8 ppm; LC90 = 716.8 ppm and LC50 = 448.3 ppm; LC90 = 803.9
      ppm, respectively). The antimicrobial properties of the nanoparticles were
      established against different clinically-isolated microbial strains and compared
      to that of the plant extract (EO) and standard antimicrobial drugs. The
      nanoparticles were generally more active than the plant extract against the
      selected microbial organisms. The Gram-negative bacterial strains Escheerichua
      coli and Salmonella typhi were more susceptible towards the nanoparticles
      compared to the Gram-positive strains and the fungal organism.

PMID- 28452945
TI  - I3Mote: An Open Development Platform for the Intelligent Industrial Internet.
AB  - In this article we present the Intelligent Industrial Internet (I3) Mote, an open
      hardware platform targeting industrial connectivity and sensing deployments. The
      I3Mote features the most advanced low-power components to tackle sensing, on
      board computing and wireless/wired connectivity for demanding industrial
      applications. The platform has been designed to fill the gap in the industrial
      prototyping and early deployment market with a compact form factor, low-cost and
      robust industrial design. I3Mote is an advanced and compact prototyping system
      integrating the required components to be deployed as a product, leveraging the
      need for adopting industries to build their own tailored solution. This article
      describes the platform design, firmware and software ecosystem and characterizes
      its performance in terms of energy consumption.

PMID- 28452947
TI  - A Consistency Evaluation and Calibration Method for Piezoelectric Transmitters.
AB  - Array transducer and transducer combination technologies are evolving rapidly.
      While adapting transmitter combination technologies, the parameter consistencies
      between each transmitter are extremely important because they can determine a
      combined effort directly. This study presents a consistency evaluation and
      calibration method for piezoelectric transmitters by using impedance analyzers.
      Firstly, electronic parameters of transmitters that can be measured by impedance
      analyzers are introduced. A variety of transmitter acoustic energies that are
      caused by these parameter differences are then analyzed and certified and,
      thereafter, transmitter consistency is evaluated. Lastly, based on the
      evaluations, consistency can be calibrated by changing the corresponding
      excitation voltage. Acoustic experiments show that this method accurately
      evaluates and calibrates transducer consistencies, and is easy to realize.

PMID- 28452946
TI  - Cytotoxic Indole Alkaloid 3alpha-Acetonyltabersonine Induces Glioblastoma
      Apoptosis via Inhibition of DNA Damage Repair.
AB  - Cytotoxic indole alkaloids from Melodinus suaveolens, which belongs to the toxic
      plant family Apocynaceae, demonstrated impressive antitumor activities in many
      tumor types, but less application in glioblastoma, which is the lethal brain
      tumor. In the present study, we reported the anti-glioblastoma activity of an
      indole alkaloid, 3alpha-acetonyltabersonine, which was isolated from Melodinus
      suaveolens. 3alpha-acetonyltabersonine was cytotoxic to glioblastoma cell lines
      (U87 and T98G) and stem cells at low concentrations. We verified 3alpha
      acetonyltabersonine could suppress tumor cell proliferation and cause apoptosis
      in glioblastoma stem cells (GSCs). Moreover, detailed investigation of
      transcriptome study and Western blotting analysis indicated the mitogen activated
      protein kinase (MAPK) pathway was activated by phosphorylation upon 3alpha
      acetonyltabersonine treatment. Additionally, we found 3alpha-acetonyltabersonine
      inhibited DNA damage repair procedures, the accumulated DNA damage stimulated
      activation of MAPK pathway and, finally, induced apoptosis. Further evidence was
      consistently obtained from vivo experiments on glioblastoma mouse model:
      treatment of 3alpha-acetonyltabersonine could exert pro-apoptotic function and
      prolong the life span of tumor-bearing mice. These results in vitro and in vivo
      suggested that 3alpha-acetonyltabersonine could be a potential candidate
      antitumor agent.

PMID- 28452948
TI  - Chemical Composition, Antioxidant and alpha-Glucosidase-Inhibiting Activities of
      the Aqueous and Hydroethanolic Extracts of Vaccinium myrtillus Leaves.
AB  - Vaccinium myrtillus (bilberry) leaf is traditionally used in southeastern Europe
      for the treatment of diabetes. In the present study, the ability of bilberry leaf
      extracts to inhibit carbohydrate-hydrolyzing enzymes and restore glutathione
      concentration in Hep G2 cells subjected to glucose-induced oxidative stress was
      investigated. A comprehensive analysis of the antioxidant activity of two
      bilberry leaf extracts was performed. The aqueous extract showed excellent total
      antioxidant and chelating activity. Its antioxidant activity in the beta-carotene
      linoleic acid assay was very good, reaching the activity of the antioxidant
      standard BHA (93.4 +/- 2.3% vs. 95.1 +/- 2.4%, respectively). The hydroethanolic
      extract (ethanol/H2O, 8:2, v/v), on the other hand, was a better radical
      scavenger and Fe2+ reducing agent. Furthermore, the aqueous extract was able to
      efficiently increase glutathione concentration in Hep G2 cells subjected to
      glucose-induced oxidative stress and restore it to the levels observed in non
      hyperglycaemic cells. The hydroethanolic extract strongly inhibited alpha
      glucosidase, with the IC50 statistically equal to the antidiabetic drug acarbose
      (0.29 +/- 0.02 mg/mL vs. 0.50 +/- 0.01 mg/mL, respectively). Phytochemical
      analysis revealed the presence of quercetin and kaemferol derivatives, as well as
      chlorogenic and p-coumaric acid. The study results indicate that V. myrtillus
      leaf may have promising properties as a supporting therapy for diabetes.

PMID- 28452949
TI  - Generation and Applications of a DNA Aptamer against Gremlin-1.
AB  - Gremlin-1, a highly conserved glycosylated and phosphorylated secretory protein,
      plays important roles in diverse biological processes including early embryonic
      development, fibrosis, tumorigenesis, and renal pathophysiology. Aptamers, which
      are RNA or DNA single-stranded oligonucleotides capable of binding specifically
      to different targets ranging from small organics to whole cells, have potential
      applications in targeted imaging, diagnosis and therapy. In this study, we
      obtained a DNA aptamer against Gremlin-1 (G-ap49) using in vitro Systematic
      Evolution of Ligands by Exponential Enrichment (SELEX). Binding assay and dot
      blot showed that G-ap49 had high affinity for Gremlin-1. Further experiments
      indicated that G-ap49 was quite stable in a cell culture system and could be used
      in South-Western blot analysis, enzyme-linked aptamer sorbent assay (ELASA), and
      aptamer-based cytochemistry and histochemistry staining to detect Gremlin-1.
      Moreover, our study demonstrated that G-ap49 is capable of revealing the
      subcellular localization of Gremlin-1. These data indicate that G-ap49 can be
      used as an alternative to antibodies in detecting Gremlin-1.

PMID- 28452950
TI  - Recent Advances in Nanomaterials for Gene Delivery-A Review.
AB  - With the rapid development of nanotechnology in the recent decade, novel DNA and
      RNA delivery systems for gene therapy have become available that can be used
      instead of viral vectors. These non-viral vectors can be made of a variety of
      materials, including inorganic nanoparticles, carbon nanotubes, liposomes,
      protein and peptide-based nanoparticles, as well as nanoscale polymeric
      materials. They have as advantages over viral vectors a decreased immune
      response, and additionally offer flexibility in design, allowing them to be
      functionalized and targeted to specific sites in a biological system with low
      cytotoxicity. The focus of this review is to provide an overview of novel
      nanotechnology-based methods to deliver DNA and small interfering RNAs into
      biological systems.

PMID- 28452951
TI  - Adverse Health Effects of Thirdhand Smoke: From Cell to Animal Models.
AB  - The newly identified smoke hazard, thirdhand smoke (THS), has gained public
      attention in recent years but its health impact and biological effects are
      largely unknown. THS may be defined by "the four Rs": tobacco chemicals that
      remain, react, re-emit, and/or are resuspended long after active smoking has
      ceased. This review summarizes recent research progress in the effects of THS on
      genotoxicity, metabolism and early life development using cellular and animal
      models. We first reported that THS generated in laboratory systems caused
      significant DNA damage in human cell lines. Our finding that THS significantly
      induces oxidative base lesions has been confirmed in skin wounds of mice models
      exposed to THS. THS also induced metabolomic changes in human reproductive cell
      lines. Furthermore, we demonstrated that early exposure to THS not only
      negatively impacts body weight in both male and female mice, but also induces
      persistent changes to immunological parameters in peripheral blood in these mice.
      These results indicate that THS is genotoxic at realistic experimental doses and
      that there may be a window of susceptibility for some forms of cellular damage
      induced by THS.

PMID- 28452952
TI  - Ultrasound Monitoring of Extant Adnexal Masses in the Era of Type 1 and Type 2
      Ovarian Cancers: Lessons Learned From Ovarian Cancer Screening Trials.
AB  - Women that are positive for an ovarian abnormality in a clinical setting can have
      either a malignancy or a benign tumor with probability favoring the benign
      alternative. Accelerating the abnormality to surgery will result in a high number
      of unnecessary procedures that will place cost burdens on the individual and the
      health delivery system. Surveillance using serial ultrasonography is a reasonable
      alternative that can be used to discover if changes in the ovarian abnormality
      will occur that favor either a malignant or benign interpretation. Several
      ovarian cancer screening trials have had extensive experiences with changes in
      subclinical ovarian abnormalities in normal women that can define growth,
      stability or resolution and give some idea of the time frame over which changes
      occur. The present report examines these experiences and relates them to the
      current understanding of ovarian cancer ontology, presenting arguments related to
      the benefits of surveillance.

PMID- 28452953
TI  - Significance of Wild-Type p53 Signaling in Suppressing Apoptosis in Response to
      Chemical Genotoxic Agents: Impact on Chemotherapy Outcome.
AB  - Our genomes are subject to potentially deleterious alterations resulting from
      endogenous sources (e.g., cellular metabolism, routine errors in DNA replication
      and recombination), exogenous sources (e.g., radiation, chemical agents), and
      medical diagnostic and treatment applications. Genome integrity and cellular
      homeostasis are maintained through an intricate network of pathways that serve to
      recognize the DNA damage, activate cell cycle checkpoints and facilitate DNA
      repair, or eliminate highly injured cells from the proliferating population. The
      wild-type p53 tumor suppressor and its downstream effector p21WAF1 (p21) are key
      regulators of these responses. Although extensively studied for its ability to
      control cell cycle progression, p21 has emerged as a multifunctional protein
      capable of downregulating p53, suppressing apoptosis, and orchestrating prolonged
      growth arrest through stress-induced premature senescence. Studies with solid
      tumors and solid tumor-derived cell lines have revealed that such growth-arrested
      cancer cells remain viable, secrete growth-promoting factors, and can give rise
      to progeny with stem-cell-like properties. This article provides an overview of
      the mechanisms by which p53 signaling suppresses apoptosis following genotoxic
      stress, facilitating repair of genomic injury under physiological conditions but
      having the potential to promote tumor regrowth in response to cancer
      chemotherapy.

PMID- 28452954
TI  - Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions.
AB  - Hydroxytyrosol (HT) ((3,4-Dihydroxyphenyl)ethanol) is a polyphenol mainly present
      in extra virgin olive oil (EVOO) but also in red wine. It has a potent
      antioxidant effect related to hydrogen donation, and the ability to improve
      radical stability. The phenolic content of olive oil varies between 100 and 600
      mg/kg, due to multiple factors (place of cultivation, climate, variety of the
      olive and level of ripening at the time of harvest), with HT and its derivatives
      providing half of that content. When consumed, EVOO's phenolic compounds are
      hydrolyzed in the stomach and intestine, increasing levels of free HT which is
      then absorbed in the small intestine, forming phase II metabolites. It has been
      demonstrated that HT consumption is safe even at high doses, and that is not
      genotoxic or mutagenic in vitro. The beneficial effects of HT have been studied
      in humans, as well as cellular and animal models, mostly in relation to
      consumption of EVOO. Many properties, besides its antioxidant capacity, have been
      attributed to this polyphenol. The aim of this review was to assess the main
      properties of HT for human health with emphasis on those related to the possible
      prevention and/or treatment of non-communicable diseases.

PMID- 28452955
TI  - Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology.
AB  - The importance of the nociceptive nervous system for maintaining tissue
      homeostasis has been known for some time, and it has also been suggested that
      organogenesis and tissue repair are under neuronal control. Changes in peripheral
      joint innervation are supposed to be partly responsible for degenerative
      alterations in joint tissues which contribute to development of osteoarthritis.
      Various resident cell types of the musculoskeletal system express receptors for
      sensory and sympathetic neurotransmitters, allowing response to peripheral
      neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts,
      bone cells and chondrocytes of different origin, which express distinct subtypes
      of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP),
      substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell
      types synthesize and secrete neuropeptides such as SP, and they are positive for
      tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of
      catecholamines. Sensory and sympathetic neurotransmitters are involved in the
      pathology of inflammatory diseases such as rheumatoid arthritis (RA) which
      manifests mainly in the joints. In addition, they seem to play a role in
      pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA).
      Altogether it is evident that sensory and sympathetic neurotransmitters have
      crucial trophic effects which are critical for joint tissue and bone homeostasis.
      They modulate articular cartilage, subchondral bone and synovial tissue
      properties in physiological and pathophysiological conditions, in addition to
      their classical neurological features.

PMID- 28452956
TI  - Protective Effect of Caffeic Acid Derivatives on tert-Butyl Hydroperoxide-Induced
      Oxidative Hepato-Toxicity and Mitochondrial Dysfunction in HepG2 Cells.
AB  - Oxidative stress results in structural and functional abnormalities in the liver
      and is thought to be a crucial factor in liver diseases. The aim of this study
      was to investigate the cytoprotective and antioxidant effects of caffeic acid
      (CA) derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in
      HepG2 cells. Nine CA derivatives were synthesized, including N-phenylethyl
      caffeamide (PECA), N-(3-florophen)methyl caffeamide (FMCA), N-(4-methoxy
      phen)methyl caffeamide (MPMCA), N-heptyl caffeamide (HCA), N-octyl caffeamide
      (OCA), octyl caffeate (CAOE), phenpropyl caffeate (CAPPE), phenethyl caffeate
      (CAPE), and phenmethyl caffeate (CAPME). The results showed that CA and its
      derivatives significantly inhibited t-BHP-induced cell death of HepG2 cells. The
      rank order of potency of the CA derivatives for cytoprotection was CAOE > HCA >
      OCA > FMCA > CAPPE > CAPME > CAPE > PECA > MPMCA > CA. Their cytoprotective
      activity was associated with lipophilicity. The antioxidant effect of these
      compounds was supported by the reduction in the levels of thiobarbituric acid
      reactive substrates, a biomarker of lipid peroxidation, in HepG2 cells. Pre
      treatment of CA derivatives significantly prevented the depletion of glutathione,
      the most important water-soluble antioxidant in hepatocytes. Pre-treatment of CA
      derivatives before t-BHP exposure maintained mitochondrial oxygen consumption
      rate and ATP content in the injured HepG2 cells. CA derivatives except OCA and
      HCA significantly suppressed t-BHP-induced hypoxia-inducible factor-1alpha (HIF
      1alpha) protein level. In addition, all of these CA derivatives markedly
      increased the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation in
      the nucleus, indicating that their cytoprotection may be mediated by the
      activation of Nrf2. Our results suggest that CA derivatives might be a
      hepatoprotective agent against oxidative stress.

PMID- 28452957
TI  - Mycotoxin Decontamination of Food: Cold Atmospheric Pressure Plasma versus
      "Classic" Decontamination.
AB  - Mycotoxins are secondary metabolites produced by several filamentous fungi, which
      frequently contaminate our food, and can result in human diseases affecting vital
      systems such as the nervous and immune systems. They can also trigger various
      forms of cancer. Intensive food production is contributing to incorrect handling,
      transport and storage of the food, resulting in increased levels of mycotoxin
      contamination. Mycotoxins are structurally very diverse molecules necessitating
      versatile food decontamination approaches, which are grouped into physical,
      chemical and biological techniques. In this review, a new and promising approach
      involving the use of cold atmospheric pressure plasma is considered, which may
      overcome multiple weaknesses associated with the classical methods. In addition
      to its mycotoxin destruction efficiency, cold atmospheric pressure plasma is cost
      effective, ecologically neutral and has a negligible effect on the quality of
      food products following treatment in comparison to classical methods.

PMID- 28452958
TI  - Palmitoleic Acid Inhibits RANKL-Induced Osteoclastogenesis and Bone Resorption by
      Suppressing NF-kappaB and MAPK Signalling Pathways.
AB  - Osteoclasts are large, multinucleated cells that are responsible for the
      breakdown or resorption of bone during bone remodelling. Studies have shown that
      certain fatty acids (FAs) can increase bone formation, reduce bone loss, and
      influence total bone mass. Palmitoleic acid (PLA) is a 16-carbon, monounsaturated
      FA that has shown anti-inflammatory properties similar to other FAs. The effects
      of PLA in bone remain unexplored. Here we investigated the effects of PLA on
      receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL)-induced
      osteoclast formation and bone resorption in RAW264.7 murine macrophages. PLA
      decreased the number of large, multinucleated tartrate resistant acid phosphatase
      (TRAP) positive osteoclasts and furthermore, suppressed the osteolytic capability
      of these osteoclasts. This was accompanied by a decrease in expression of
      resorption markers (Trap, matrix metalloproteinase 9 (Mmp9), cathepsin K (Ctsk)).
      PLA further decreased the expression of genes involved in the formation and
      function of osteoclasts. Additionally, PLA inhibited NF-kappaB activity and the
      activation of mitogen activated protein kinases (MAPK), c-Jun N-terminal kinase
      (JNK) and extracellular signal-regulated kinase (ERK). Moreover, PLA induced
      apoptosis in mature osteoclasts. This study reveals that PLA inhibits RANKL
      induced osteoclast formation in RAW264.7 murine macrophages through suppression
      of NF-kappaB and MAPK signalling pathways. This may indicate that PLA has
      potential as a therapeutic for bone diseases characterized by excessive
      osteoclast formation.

PMID- 28452959
TI  - Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast
      Cancer: the Role of NF-kappaB and Nrf2 Signaling Pathways.
AB  - Pomegranate (Punica granatum L.), a nutrient-rich unique fruit, has been used for
      centuries for the prevention and treatment of various inflammation-driven
      diseases. Based on our previous study, a characterized pomegranate emulsion (PE)
      exhibited a striking inhibition of dimethylbenz(a)anthracene (DMBA)-initiated rat
      mammary tumorigenesis via antiproliferative and apoptosis-inducing mechanisms.
      The objective of the present work is to investigate the anti-inflammatory
      mechanism of action of PE during DMBA rat mammary carcinogenesis by evaluating
      the expression of cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90),
      nuclear factor-kappaB (NF-kappaB) and nuclear factor erythroid 2p45 (NF-E2)
      related factor 2 (Nrf2). Mammary tumor samples were harvested from our previous
      chemopreventive study in which PE (0.2-5.0 g/kg) was found to reduce mammary
      tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF
      kappaB, inhibitory kappaBalpha (IkappaBalpha) and Nrf2 were detected by
      immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90,
      prevented the degradation of IkappaBalpha, hindered the translocation of NF
      kappaB from cytosol to nucleus and increased the expression and nuclear
      translocation of Nrf2 during DMBA-induced mammary tumorigenesis. These findings,
      together with our previous results, indicate that PE-mediated prevention of DMBA
      evoked mammary carcinogenesis may involve anti-inflammatory mechanisms through
      concurrent but differential regulation of two interrelated molecular pathways,
      namely NF-kappaB and Nrf2 signaling.

PMID- 28452960
TI  - Distribution of Constituents and Metabolites of Maritime Pine Bark Extract
      (Pycnogenol(r)) into Serum, Blood Cells, and Synovial Fluid of Patients with
      Severe Osteoarthritis: A Randomized Controlled Trial.
AB  - The present randomized controlled study aimed to investigate the in vivo
      distribution of constituents or metabolites of the standardized maritime pine
      bark extract Pycnogenol(r). Thirty-three patients with severe osteoarthritis
      scheduled for a knee arthroplasty were randomized to receive either 200 mg per
      day Pycnogenol(r) (P+) or no treatment (Co) over three weeks before surgery.
      Serum, blood cells, and synovial fluid samples were analyzed using liquid
      chromatography coupled to tandem mass spectrometry with electrospray ionization
      (LC-ESI/MS/MS). Considerable interindividual differences were observed indicating
      pronounced variability of the polyphenol pharmacokinetics. Notably, the highest
      polyphenol concentrations were not detected in serum. Catechin and taxifolin
      primarily resided within the blood cells while the microbial catechin metabolite
      delta-(3,4-dihydroxy-phenyl)-gamma-valerolactone, ferulic, and caffeic acid were
      mainly present in synovial fluid samples. Taxifolin was detected in serum and
      synovial fluid exclusively in the P+ group. Likewise, no ferulic acid was found
      in serum samples of the Co group. Calculating ratios of analyte distribution in
      individual patients revealed a simultaneous presence of some polyphenols in
      serum, blood cells, and/or synovial fluid only in the P+ group. This is the first
      evidence that polyphenols distribute into the synovial fluid of patients with
      osteoarthritis which supports rationalizing the results of clinical efficacy
      studies.

PMID- 28452963
TI  - Bioresponsive Materials for Drug Delivery Based on Carboxymethyl
      Chitosan/Poly(gamma-Glutamic Acid) Composite Microparticles.
AB  - Carboxymethyl chitosan (CMCS) microparticles are a potential candidate for
      hemostatic wound dressing. However, its low swelling property limits its
      hemostatic performance. Poly(gamma-glutamic acid) (PGA) is a natural polymer with
      excellent hydrophilicity. In the current study, a novel CMCS/PGA composite
      microparticles with a dual-network structure was prepared by the
      emulsification/internal gelation method. The structure and thermal stability of
      the composite were determined by Fourier transform infrared spectroscopy (FTIR),
      X-ray powder diffraction (XRD), scanning electron microscope (SEM), X-ray
      photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The
      effects of preparation conditions on the swelling behavior of the composite were
      investigated. The results indicate that the swelling property of CMCS/PGA
      composite microparticles is pH sensitive. Levofloxacin (LFX) was immobilized in
      the composite microparticles as a model drug to evaluate the drug delivery
      performance of the composite. The release kinetics of LFX from the composite
      microparticles with different structures was determined. The results suggest that
      the CMCS/PGA composite microparticles are an excellent candidate carrier for drug
      delivery.

PMID- 28452961
TI  - Relationship of the Reported Intakes of Fat and Fatty Acids to Body Weight in US
      Adults.
AB  - Dietary fat composition may modulate energy expenditure and body weight. Little
      is known about the relationship between fatty acid intake and body weight at a
      population level. The purposes of this study were to compare intakes of energy,
      macronutrients, and individual fatty acids across BMI categories (1) for the US
      adult population and, (2) by sociodemographic groups. Reported dietary intake
      data from the National Health and Nutrition Examination Survey (NHANES) and What
      We Eat in America (WWEIA) surveys in the years 2005-2012 were analyzed. Overall,
      we found that the reported intake of carbohydrate, protein, total fat, total
      saturated fat (as well as long-chain saturated fatty acids 14:0-18:0), and
      monounsaturated fatty acids (MUFAs) were positively associated with BMI; while
      lauric acid (a medium-chain saturated fatty acid, 12:0) and total polyunsaturated
      fatty acids (PUFAs) (as well as all individual PUFAs) were not associated with
      BMI. Non-Hispanic black individuals demonstrated a negative association between
      BMI and energy intake and a positive association between total PUFAs, linoleic
      acid (LA), alpha-linolenic acid (ALA) and BMI. Individuals with less than a high
      school education showed a negative association between BMI and DHA. Mexican
      Americans reported intakes with no association between BMI and energy, any
      macronutrient, or individual fatty acids. These findings support those of
      experimental studies demonstrating fatty acid-dependent associations between
      dietary fatty acid composition and body weight. Notably, we observed divergent
      results for some sociodemographic groups which warrant further investigation.

PMID- 28452962
TI  - Trace Elements in Parenteral Nutrition: Considerations for the Prescribing
      Clinician.
AB  - Trace elements (TEs) are an essential component of parenteral nutrition (PN).
      Over the last few decades, there has been increased experience with PN, and with
      this knowledge more information about the management of trace elements has become
      available. There is increasing awareness of the effects of deficiencies and
      toxicities of certain trace elements. Despite this heightened awareness, much is
      still unknown in terms of trace element monitoring, the accuracy of different
      assays, and current TE contamination of solutions. The supplementation of TEs is
      a complex and important part of the PN prescription. Understanding the role of
      different disease states and the need for reduced or increased doses is
      essential. Given the heterogeneity of the PN patients, supplementation should be
      individualized.

PMID- 28452965
TI  - Neuroprotective and Cognitive Enhancement Potentials of Angelica gigas Nakai
      Root: A Review.
AB  - Angelica gigas Nakai is an important medicinal plant with health promoting
      properties that is used to treat many disorders. In traditional herbal medicine,
      the root of this plant is used to promote blood flow, to treat anemia, and is
      used as sedative or tonic agent. The root contains various bioactive metabolites;
      in particular, decursin and decursinol (pyranocoumarin type components) have been
      reported to possess various pharmacological properties. Recently, several in
      vitro and in vivo studies have reported that the crude extracts and isolated
      components from the root of A. gigas exhibited neuroprotective and cognitive
      enhancement effects. Neuronal damage or death is the most important factor for
      many neurodegenerative diseases. In addition, recent studies have clearly
      demonstrated the possible mechanisms behind the neuroprotective action of
      extracts/compounds from the root of A. gigas. In the present review, we
      summarized the neuroprotective and cognitive enhancement effects of extracts and
      individual compounds from A. gigas root. 

PMID- 28452964
TI  - Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular
      Targets.
AB  - Among the complex determinants of aging, mitochondrial dysfunction has been in
      the spotlight for a long time. As the hub for many cellular functions, the
      maintenance of an adequate pool of functional mitochondria is crucial for tissue
      homeostasis. Their unique role in energy supply makes these organelles essential,
      especially in those tissues strictly dependent on oxidative metabolism.
      Mitochondrial quality control (MQC) is ensured by pathways related to protein
      folding and degradation as well as by processes involving the entire organelle,
      such as biogenesis, dynamics, and mitophagy. Dysfunctional MQC, oxidative stress
      and inflammation are hallmarks of senescence and chronic degenerative diseases.
      One of the consequences of age-related failing MQC and oxidative stress is the
      release of mitochondria-derived damage-associated molecular patterns (DAMPs).
      Through their bacterial ancestry, these molecules contribute to mounting an
      inflammatory response by interacting with receptors similar to those involved in
      pathogen-associated responses. Mitochondrial DAMPs, especially cell-free
      mitochondrial DNA, have recently become the subject of intensive research because
      of their possible involvement in conditions associated with inflammation, such as
      aging and degenerative diseases. Here, we review the contribution of
      mitochondrial DAMPs to inflammation and discuss some of the mechanisms at the
      basis of their generation.

PMID- 28452966
TI  - Electrochemical Enhancement of Photocatalytic Disinfection on Aligned TiO2 and
      Nitrogen Doped TiO2 Nanotubes.
AB  - TiO2 photocatalysis is considered as an alternative to conventional disinfection
      processes for the inactivation of waterborne microorganisms. The efficiency of
      photocatalysis is limited by charge carrier recombination rates. When the
      photocatalyst is immobilized on an electrically conducting support, one may
      assist charge separation by the application of an external electrical bias. The
      aim of this work was to study electrochemically assisted photocatalysis with
      nitrogen doped titania photoanodes under visible and UV-visible irradiation for
      the inactivation of Escherichia coli. Aligned TiO2 nanotubes were synthesized
      (TiO2-NT) by anodizing Ti foil. Nanoparticulate titania films were made on Ti
      foil by electrophoretic coating (P25 TiO2). N-doped titania nanotubes and N,F co
      doped titania films were also prepared with the aim of extending the active
      spectrum into the visible. Electrochemically assisted photocatalysis gave higher
      disinfection efficiency in comparison to photocatalysis (electrode at open
      circuit) for all materials tested. It is proposed that electrostatic attraction
      of negatively charged bacteria to the positively biased photoanodes leads to the
      enhancement observed. The N-doped TiO2 nanotube electrode gave the most efficient
      electrochemically assisted photocatalytic inactivation of bacteria under UV-Vis
      irradiation but no inactivation of bacteria was observed under visible only
      irradiation. The visible light photocurrent was only a fraction (2%) of the UV
      response.

PMID- 28452967
TI  - Evaluation of Rational Drug Use for Acute Pharyngitis Associated with the
      Incidence and Prevalence of the Disease at Two Community Health Centers in
      Indonesia.
AB  - According to Indonesia's Result of Basic Health Research of 2013, prevalence of
      acute respiratory infection in 2007 and 2013 were not significantly different
      (25.5% and 25.0%, respectively). Identifying the cause of acute pharyngitis is a
      key point in determining the optimal treatment. The main purpose is to evaluate
      the rational use of drugs and its irrational impact as well as the correlation of
      the drug use with the incidence and prevalence of acute pharyngitis. This study
      was a descriptive and observational study, carried out retrospectively and
      concurrently at two community health centers located in Bandung and Cimahi,
      Indonesia. There was overprescription of antibiotics in 80.01% of prescription
      cases, with a total of 8.98% being non-treatment option, and 62.43% being
      irrational use of corticosteroids. The incidence and prevalence of acute
      pharyngitis at one health center in Bandung were 2.45% and 2.31%, respectively,
      with an irrationality rate of 83.82%. Those recorded at one health center in
      Cimahi were 2.11% incidence and 2.00% prevalence with an irrational rate of
      91.29%. It can be concluded that there is still an irrational use of medicines in
      the treatment of acute pharyngitis in community health centers. The higher
      incidence and prevalence might indicate the declining quality of health services.

PMID- 28452968
TI  - Immunomodulatory effect of stereotactic ablative radiotherapy in lung cancer.

PMID- 28452969
TI  - Prognostic scores in advanced heart failure: where are we now and where are we
      going?

PMID- 28452970
TI  - One-year survival of ambulatory patients with end-stage heart failure: the
      analysis of prognostic factors.
AB  - INTRODUCTION    An increasing number of ambulatory patients are placed on
      orthotopic heart transplantation (OHT) waiting lists, which results in an
      extended waiting time and a higher mortality rate. OBJECTIVES    The aim of this
      study was to identify the factors associated with reduced survival during a 1
      year follow-up in patients with end-stage heart failure listed for an OHT.
      PATIENTS AND METHODS    We retrospectively analyzed the data of 221 adult
      patients, who were accepted for OHT in our institution over a 2-year period
      between 2013 and 2014. RESULTS    The mean (SD) age of the patients was 54.7
      (9.6) years, and 90.1% of them were male. The mortality rate during the follow-up
      period was 43.3%. The modified Model for End-Stage Liver Disease (modMELD) score
      (odds ratio [OR], 1.70; P <0.001), as well as the plasma levels of high
      sensitivity C-reactive protein (hs-CRP; OR, 1.10; P <0.01), sodium (OR, 0.74; P
      <0.001), and uric acid (UA; OR, 1.003; P <0.05) were independent factors
      affecting death. The receiver-operating characteristic (ROC) analysis indicated
      that a modMELD cut-off of 10 (area under the ROC curve [AUC], 0.868; P <0.001),
      hs-CRP cut-off of 5.6 mg/l (AUC, 0.674; P <0.001), plasma sodium level cut-off of
      135 mmol/l (AUC, 0.778; P <0.001), and a plasma UA cut-off of 488 MUmol/l (AUC,
      0.634; P <0.001) were the most accurate factors affecting death. CONCLUSIONS   
      In conclusion, although limited to a single center, our study demonstrated that
      an elevated modMELD score, incorporating a combination of renal and hepatic
      laboratory parameters, as well as plasma sodium, UA, and hs-CRP levels at the
      time of listing are associated with reduced survival in ambulatory patients with
      end-stage heart failure, accepted for OHT.

PMID- 28452971
TI  - Gas bubbles in the pericardium and concomitant tricuspid valve mass.

PMID- 28452972
TI  - Pulmonary embolism in a patient with mild factor VII deficiency after
      administration of recombinant activated factor VII during a urological procedure.

PMID- 28452974
TI  - Challenges of managing asthma in an elderly population.

PMID- 28452973
TI  - Learning to touch the patient's soul: a difficult lesson from the Netherlands.

PMID- 26035428
TI  - Are statins beneficial for chronic heart failure? First update.
AB  - This Living FRISBEE (Living FRIendly Summary of the Body of Evidence using
      Epistemonikos) is an update of an article published in May 2015 (doi:
      10.5867/medwave.2015.04.6140), based on the detection of nine new systematic
      reviews. Even though statins decrease inflammatory markers and improve some
      echocardiographic parameters in heart failure, it is not clear whether they have
      an impact on clinically important outcomes. Searching in Epistemonikos database,
      which is maintained by screening multiple databases, we identified 14 systematic
      reviews including 25 randomized trials answering the question of interest. We
      extracted data, combined the evidence using meta-analysis and generated a summary
      of findings table following the GRADE approach. We concluded statins do not
      decrease mortality in chronic heart failure, and might lead to a small reduction
      in hospital admissions for heart failure, but the certainty of this evidence is
      low.

PMID- 28452976
TI  - Is chondroitin sulfate effective for osteoarthritis?
AB  - Osteoarthritis is the most prevalent chronic articular disease, in which pain is
      one of the main symptoms and the major determinant of functional loss. Several
      therapeutic options have been proposed, including chondroitin sulfate, but its
      actual usefulness has not yet been established. To answer this question we
      searched in Epistemonikos database, which is maintained by screening multiple
      information sources. We identified 13 systematic reviews including 50 randomized
      trials overall. We extracted data, conducted a meta-analysis and generated a
      summary of findings table using the GRADE approach. We concluded it is not clear
      whether the use of chondroitin sulfate leads to an improvement in pain or
      functionality in osteoarthritis because the certainty of the evidence is very
      low.

PMID- 28452977
TI  - Is it worth adding an inferior vena cava filter to anticoagulation in
      thromboembolic disease?
AB  - Some patients who have presented a thromboembolic event persist with a high risk
      of recurrence despite anticoagulant treatment. It has been suggested that adding
      an inferior vena cava filter may reduce this risk, but the clinical effects of
      this measure are not clear. To answer this question we searched in Epistemonikos
      database, which is maintained by screening multiple information sources. We
      identified three systematic reviews including four randomized trials answering
      this question. We extracted data, conducted a meta-analysis and generated a
      summary of findings table using the GRADE approach. We concluded there might be
      little or no difference on the occurrence of deep venous thrombosis by adding an
      inferior vena cava filter in anticoagulated patients, and it is not clear whether
      there are differences in the occurrence of pulmonary embolism or mortality
      because the certainty of evidence is very low.

PMID- 28452978
TI  - Risk factors for acute kidney injury in a pediatric intensive care unit: a
      retrospective cohort study.
AB  - BACKGROUND: The incidence of acute kidney injury in the pediatric population and
      its associated risk factors are currently not clear. OBJECTIVES: The objective of
      the study was to assess the incidence of acute kidney injury in critically ill
      pediatric patients and to determine its associated risk factors. METHODS: We
      conducted a retrospective study of pediatric patients (<14 years old) admitted to
      a tertiary pediatric intensive care unit. Acute kidney injury (AKI) was
      classified using the Kidney Disease: Improving Global Outcomes definition KDIGO.
      RESULTS: A total number of 382 patients were assessed: acute kidney injury was
      found in 11.5% of them (incidence rate 0.99 persons-day). The following
      parameters analyzed with multivariate regression analysis were associated with
      acute kidney injury: low platelet count (R = 2.947; 95% CI= 1.276-6.805) and the
      need of vasopressor support (OR= 4.601; 95% CI= 1.665-12.710). Children with
      acute kidney injury had an increased length of stay in the hospital and an
      increased mortality compared with patients with no kidney injury (19 days vs. 5
      days and 3.7/person-day vs. 0.32/person-day). CONCLUSIONS: Acute kidney injury is
      common among critically ill children and it is associated with adverse outcomes,
      including increased length of stay in the hospital and death. Low platelet count
      and vasopressor support were independently associated with the development of
      acute kidney injury in this population.

PMID- 28452980
TI  - Corrigendum: Lipopolysaccharide-Induced Neutrophil Dysfunction Following
      Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Insertion is
      Associated with Organ Failure and Mortality.

PMID- 28452979
TI  - Structural basis for lambdaN-dependent processive transcription antitermination.
AB  - lambdaN-mediated processive antitermination constitutes a paradigmatic
      transcription regulatory event, during which phage protein lambdaN, host factors
      NusA, NusB, NusE and NusG, and an RNA nut site render elongating RNA polymerase
      termination-resistant. The structural basis of the process has so far remained
      elusive. Here we describe a crystal structure of a lambdaN-NusA-NusB-NusE-nut
      site complex and an electron cryo-microscopic structure of a complete
      transcription antitermination complex, comprising RNA polymerase, DNA, nut site
      RNA, all Nus factors and lambdaN, validated by crosslinking/mass spectrometry.
      Due to intrinsic disorder, lambdaN can act as a multiprotein/RNA interaction hub,
      which, together with nut site RNA, arranges NusA, NusB and NusE into a triangular
      complex. This complex docks via the NusA N-terminal domain and the lambdaN C
      terminus next to the RNA exit channel on RNA polymerase. Based on the structures,
      comparative crosslinking analyses and structure-guided mutagenesis, we
      hypothesize that lambdaN mounts a multipronged strategy to reprogram the
      transcriptional machinery, which may include (1) the lambdaN C terminus clamping
      the RNA exit channel, thus stabilizing the DNA:RNA hybrid; (2) repositioning of
      NusA and RNAP elements, thus redirecting nascent RNA and sequestering the
      upstream branch of a terminator hairpin; and (3) hindering RNA engagement of
      termination factor rho and/or obstructing rho translocation on the transcript.

PMID- 28452981
TI  - Host response: Pregnancy impairs flu defences.

PMID- 28452982
TI  - Corrigendum: Arbuscular mycorrhiza enhance the rate of litter decomposition while
      inhibiting soil microbial community development.

PMID- 28452983
TI  - Convergent evolution of a modified, acetate-driven TCA cycle in bacteria.
AB  - The tricarboxylic acid (TCA) cycle is central to energy production and
      biosynthetic precursor synthesis in aerobic organisms. There are few known
      variations of a complete TCA cycle, with the common notion being that the enzymes
      involved have already evolved towards optimal performance. Here, we present
      evidence that an alternative TCA cycle, in which acetate:succinate CoA
      transferase (ASCT) replaces the enzymatic step typically performed by succinyl
      CoA synthetase (SCS), has arisen in diverse bacterial groups, including microbial
      symbionts of animals such as humans and insects.

PMID- 28452985
TI  - Through translational prospective study, the GSTP1 Ile105Val polymorphism emerges
      as prognostic marker in de novo large B-cell lymphoma patients.

PMID- 28452986
TI  - Vaccines, science and trust.

PMID- 28452984
TI  - Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic
      myeloid leukemia.
AB  - Although tyrosine kinase inhibitors (TKIs) have significantly improved the
      prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML
      remains uncertain and patients must continue TKI therapy for indefinite periods.
      In this study, we performed whole-exome sequencing to identify somatic mutations
      in 24 patients with newly diagnosed chronic phase CML who were registered in the
      JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1
      fusion gene (median 8, range 1-17). Age, hemoglobin concentration and white blood
      cell counts were correlated with the number of mutations. Patients with mutations
      ?6 showed higher rate of achieving major molecular response than those<6
      (P=0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6
      were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one
      patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were
      significantly enriched with cell signaling and cell division pathways.
      Furthermore, DNA copy number analysis showed that 2 of 24 patients had
      uniparental disomy of chromosome 1p or 3q, which disappeared major molecular
      response was achieved. These mutations may play significant roles in CML
      pathogenesis in addition to the strong driver mutation BCR-ABL1.

PMID- 28452987
TI  - Variability and host density independence in inductions-based estimates of
      environmental lysogeny.
AB  - Temperate bacterial viruses (phages) may enter a symbiosis with their host cell,
      forming a unit called a lysogen. Infection and viral replication are
      disassociated in lysogens until an induction event such as DNA damage occurs,
      triggering viral-mediated lysis. The lysogen-lytic viral reproduction switch is
      central to viral ecology, with diverse ecosystem impacts. It has been argued that
      lysogeny is favoured in phages at low host densities. This paradigm is based on
      the fraction of chemically inducible cells (FCIC) lysogeny proxy determined using
      DNA-damaging mitomycin C inductions. Contrary to the established paradigm, a
      survey of 39 inductions publications found FCIC to be highly variable and
      pervasively insensitive to bacterial host density at global, within-environment
      and within-study levels. Attempts to determine the source(s) of variability
      highlighted the inherent complications in using the FCIC proxy in mixed
      communities, including dissociation between rates of lysogeny and FCIC values.
      Ultimately, FCIC studies do not provide robust measures of lysogeny or consistent
      evidence of either positive or negative host density dependence to the lytic
      lysogenic switch. Other metrics are therefore needed to understand the drivers of
      the lytic-lysogenic decision in viral communities and to test models of the host
      density-dependent viral lytic-lysogenic switch.

PMID- 28452988
TI  - Nanoscale movements of cellulose microfibrils in primary cell walls.
AB  - The growing plant cell wall is commonly considered to be a fibre-reinforced
      structure whose strength, extensibility and anisotropy depend on the orientation
      of crystalline cellulose microfibrils, their bonding to the polysaccharide matrix
      and matrix viscoelasticity1-4. Structural reinforcement of the wall by stiff
      cellulose microfibrils is central to contemporary models of plant growth,
      mechanics and meristem dynamics4-12. Although passive microfibril reorientation
      during wall extension has been inferred from theory and from bulk measurements13
      15, nanometre-scale movements of individual microfibrils have not been directly
      observed. Here we combined nanometre-scale imaging of wet cell walls by atomic
      force microscopy (AFM) with a stretching device and endoglucanase treatment that
      induces wall stress relaxation and creep, mimicking wall behaviours during cell
      growth. Microfibril movements during forced mechanical extensions differ from
      those during creep of the enzymatically loosened wall. In addition to passive
      angular reorientation, we observed a diverse repertoire of microfibril movements
      that reveal the spatial scale of molecular connections between microfibrils. Our
      results show that wall loosening alters microfibril connectivity, enabling
      microfibril dynamics not seen during mechanical stretch. These insights into
      microfibril movements and connectivities need to be incorporated into refined
      models of plant cell wall structure, growth and morphogenesis.

PMID- 28452989
TI  - Osmoprotectants, carboxymethylcellulose and hyaluronic acid multi-ingredient eye
      drop: a randomised controlled trial in moderate to severe dry eye.
AB  - PurposeTo assess the safety and efficacy of an eye drop combining
      osmoprotectants, carboxymethylcellulose and hyaluronic acid (O/CMC/HA) in
      reducing symptomatic, moderate to severe dry eye, compared with HA.MethodsIn this
      investigator-masked, randomised study, patients instilled 1-2 drops/eye of
      O/CMC/HA or HA (2-6 times/day) for 3 months. Primary endpoint: mean change in
      Global Ocular Staining Score (GOSS) from baseline at day 35. Noninferiority of
      O/CMC/HA was tested in the per-protocol population; if achieved, superiority was
      tested in the intent-to-treat population. Secondary efficacy endpoints: mean
      change from baseline in GOSS, Ocular Surface Disease Index (OSDI), Schirmer
      score, tear break-up time (TBUT), corneal/conjunctival staining, conjunctival
      hyperaemia, symptoms, and patient/investigator assessments.ResultsBaseline
      characteristics were comparable between groups (n=40 each). O/CMC/HA was
      noninferior (and not superior) to HA based on similar GOSS reductions from
      baseline at day 35 and month 3 in both groups (P=0.778, day 35, per-protocol
      population). Overall, O/CMC/HA and HA provided similar reductions in OSDI,
      Schirmer score, TBUT, corneal staining and hyperaemia from baseline at 35 days
      (P>=0.155). More patients reported less severe stinging/burning,
      sandiness/grittiness, and painful/sore eyes at month 3 with O/CMC/HA (P<=0.039),
      and more rated the dropper bottle easy to use (87.5%), compared with HA (46.2%;
      P=0.002). Other patient and investigator assessments were similar between groups.
      O/CMC/HA and HA were well tolerated.ConclusionsO/CMC/HA is noninferior to HA in
      improving objective signs of dry eye, with potential advantages for subjective
      symptoms and patient acceptance.

PMID- 28452990
TI  - Relationship between the optic nerve sheath diameter and lumbar cerebrospinal
      fluid pressure in patients with normal tension glaucoma.
AB  - PurposeTo investigate on the relationship between the optic nerve sheath diameter
      (ONSD) and the lumbar cerebrospinal fluid pressure (CSF-p) in Caucasian patients
      with normal tension glaucoma (NTG).Patients and methodsRetrospective analysis of
      medical records of patients with open-angle glaucoma in the period from 2005 to
      2015 from the Ophthalmology Department, Cantonal Hospital Aarau, Switzerland was
      performed. A total of 38 patients (mean age 68.6+/-11.3 years, 21 females and 17
      males) fulfilled the diagnostic criteria of NTG and underwent computed tomography
      (CT) of the orbit and lumbar puncture (LP). In total, 38 age- and gender-matched
      Caucasian subjects (mean age: 68.9+/-10.9 years) without known ON diseases served
      as controls for ONSD measurements. ONSDs were measured at a distance of 3 mm from
      the posterior globe and lumbar CSF-p was related to the measurements. Statistical
      analysis was performed by using the independent two-tailed t-test and the non
      parametric Spearman's correlation test.ResultsThe mean ONSD in NTGs measured
      6.4+/-0.9 mm and in controls 5.4+/-0.6 mm. The difference between NTGs and
      controls showed statistical significance (t-test: P<0.000). The mean CSF-p in NTG
      was 11.6+/-3.7 mm Hg. There was no statistical significant correlation between
      ONSD and CSF-p (Spearman's correlation coefficient rho=0.06,
      P=0.72).ConclusionsThis study demonstrates enlarged ONSDs and normal lumbar CSF-p
      in 38 Caucasian NTG patients. As enlarged ONSDs generally are associated with
      increased intracranial CSF-p, these results can be explained by a disturbed
      communication of CSF-p between the intracranial and intraorbital subarachnoid
      spaces.

PMID- 28452991
TI  - Focal choroidal excavation-morphological features and clinical correlation.
AB  - PurposeTo describe and correlate the morphological and clinical features of focal
      choroidal excavation (FCE).MethodsThis is a consecutive case series from the
      review of the 4436 optical coherence tomography scans performed by Kowloon East
      Cluster Ophthalmic Service from 1 August 2014-31 January 2016. Statistical
      analysis was performed on SPSS 18.0 (SPSS, Chicago, IL, USA). A significance
      level of P<0.05 was taken.ResultsAll 16 patients with FCE had unilateral
      involvement. The mean age of diagnosis was 52.56+/-14.00. The mean greatest
      linear dimension (GLD) of FCE was 636.25+/-265.11 MUm. The mean choroidal
      thickness was 183.63+/-52.39 MUm. Fourteen FCEs (87.5%) were conforming and two
      were non-conforming (12.5%). In the eyes with FCE, concurrent macular pathology
      was present in four cases (25.0%). Tractional pathologies of macular pucker and
      macular scar corresponded to the two non-conforming FCEs in the series.
      Polypoidal choroidal vasculopathy (PCV) and lacquer crack had a close topographic
      relationship with the FCE. The mean GLD was significantly larger in eyes with
      concurrent macular pathology than those without (878.00 vs 555.67 MUm, P=0.029).
      In the fellow eyes, concurrent macular pathology was present in 5 cases (31.3%):
      PCV in 3 cases and chronic central serous chorioretinopathy in 2
      cases.ConclusionAs a significant proportion of FCE is associated with concurrent
      macular pathology in the involved or fellow eye, angiography for both eyes is
      recommended even for asymptomatic cases. The GLD of FCE may have clinical value
      in risk stratification.

PMID- 28452992
TI  - Influence of baseline diabetic retinopathy status on initial anatomical response
      of intravitreal ranibizumab therapy for diabetic macular oedema.
AB  - PurposeIntraocular vascular endothelial growth factor (VEGF) levels increases
      with the severity of diabetic retinopathy. Response of diabetic macular oedema
      (DMO) to ranibizumab is driven by VEGF suppression. We hypothesised that the
      initial reduction of central macular thickness by ranibizumab should be maximum
      in severe diabetic retinopathy until the levels of VEGF decreases to the levels
      observed in eyes with mild retinopathy.MethodsConsecutive patients with centre
      involving DMO (central subfield thickness (CSFT)>300 MUm) who had three
      consecutive monthly ranibizumab injections followed by as needed therapy were
      included. Retinopathy status was graded as mild non-proliferative diabetic
      retinopathy (NPDR) (G1), moderate to severe NPDR with no prior panretinal
      photocoagulation (G2), and treated PDR (G3).ResultsTwo hundred and thirty-nine
      eyes from 204 patients with a mean age of 64.9 years were included. The
      distribution was 31.4 G1, 32.2 G2, and 36.4% G3. Mean baseline CSFT for all eyes
      was 458.5+/-110.8 MUm. Baseline CSFT for G1, G2, and G3, respectively, were
      437.6+/-90.9, 472.3+/-109.8, and 464.7+/-124.9 MUm (P=0.2155). Mean change in
      CSFT after three consecutive injections was 128.5+/-116.6 MUm. The mean changes
      were 95.8+/-101.4 MUm for G1, 137.2+/-112.9 MUm for G2, and 148.9+/-126.9 MUm for
      G3. The changes in CSFT between groups adjusted for baseline CSFT were
      statistically significant (P=0.0473). At 6 and 12 months after a mean of 4.5 and
      7.7 injections, the changes between groups were no longer significant, P=0.4783
      and P=0.8271, respectively.ConclusionsThe initial anatomical response of DMO with
      intravitreal ranibizumab injections was maximum in eyes with treated PDR,
      suggesting that the higher the VEGF levels, the better the response with
      ranibizumab.

PMID- 28452993
TI  - Structural and functional changes to the retina and optic nerve following
      panretinal photocoagulation over a 2-year time period.
AB  - PurposeTo evaluate long-term structural and functional changes to the retina and
      optic nerve following panretinal photocoagulation (PRP) in diabetic retinopathy
      (DR) patients.MethodsParticipants were patients with DR requiring PRP and control
      patients with DR not requiring PRP. The Heidelberg retinal tomography (HRT) and
      optical coherence tomography (OCT) were performed to analyze the optic nerve and
      macula. Best-corrected visual acuity (BCVA) and visual field (VF) testing were
      done to measure central and peripheral vision. Wide-field fluorescein angiogram
      was performed to monitor the progression of diabetic ischemia. The primary
      outcome measure was to determine the degree of retinal and optic nerve changes
      before and after PRP.ResultsThere was a non-significant thickening of the macula
      and retinal nerve fiber layer at 6 months post laser that recovered by 24 months.
      Mean perfused ratio was significantly increased (P=0.02) at 12 and 24 months post
      laser. Independently grading patient stereophotographs, grader 1 indicated there
      was a non-significant increase in cup to disk ratio post laser, while grader 2
      indicated a significant increase at 6 (P=0.04), 12 (P=0.02), and 24 months
      (P=0.005). There was a significant VF decrease (P<=0.02) at 12 and 24 months post
      laser with BCVA showing a non-significant trend of deteriorating
      results.ConclusionDespite an improvement in peripheral perfusion, there was a
      significant progressive decline of peripheral VF over the study period. Clinical
      grading of the optic nerve was more unreliable following PRP, despite the absence
      of significant morphological changes as detected by the OCT and HRT.

PMID- 28452994
TI  - Oxidative stress and diabetic retinopathy: development and treatment.
AB  - Diabetic retinopathy (DR) is the most common microvascular complication in
      diabetic patients and one of the main causes of acquired blindness in the world.
      From the 90s until date, the incidence of this complication has increased.
      Reactive oxygen species (ROS) is a free radical with impaired electron that
      usually participates in the redox mechanisms of some body molecules such as
      enzymes, proteins, and so on. In normal biological conditions, ROS is maintained
      in equilibrium, however its overproduction can lead to biological process called
      oxidative stress and this is considered the main pathogenesis of DR. The retina
      is susceptible to ROS because of high-energy demands and exposure to light. When
      the balance is broken, ROS produces retinal cell injury by interacting with the
      cellular components. This article describes the possible role of oxidative stress
      in the development of DR and proposes some treatment options based on its stages.
      The review of the topic shows that blindness caused by DR can be avoided by early
      detection and timely treatment.

PMID- 28452995
TI  - Twelve-year analysis of microbial keratitis trends at a UK tertiary hospital.
AB  - PurposeTo investigate the frequencies, trends, and in vitro drug susceptibilities
      of the causative pathogens in microbial keratitis in Manchester Royal Eye
      Hospital.Patients and methodsCorneal scrape results recorded by the microbiology
      service between 2004 and 2015 were extracted from an established database. A
      total of 4229 corneal scrape specimens were identified from an established
      database. First-line antibiotic treatment in our centre during the study period
      was ofloxacin and second line was cefuroxime and gentamicin.ResultsMean age was
      45.9+/-21.0. A total of 1379 samples (32.6%) were culture positive. One hundred
      forty-eight (10.7%) specimens cultured multiple organisms. Of the 1539 organisms
      identified, 63.3% were Gram-positive bacteria, 27.3% Gram-negative bacteria, 7.1%
      fungi, and 2.3% Acanthamoebae. A decreasing trend in Gram-positive isolates was
      found together with a stable trend in Gram negatives and an increasing trend in
      Acanthamoeba and fungi. There appeared to be a significant increasing trend of
      Moraxella infection (P=0.001). In all, 83.1 and 90.8% of Gram-positive and 
      negative isolates tested were susceptible to ofloxacin, respectively. Cefuroxime
      covered 86.6% of Gram-positive and 61.4% of Gram-negative isolates, whereas
      gentamicin covered 88.8 and 96.5% of Gram-positive and -negative isolates,
      respectively.ConclusionWe found a change in the type of Gram-negative organisms
      isolated over time, with the Moraxella species on the rise. Reassuringly, no
      significant increase in resistance was observed in vitro for any of the commonly
      used antibiotics. Ofloxacin remains a good first-line antibiotic treatment but
      duo-therapy does have broader coverage and should be considered in non-responsive
      cases.

PMID- 28452996
TI  - When PERK inhibitors turn out to be new potent RIPK1 inhibitors: critical issues
      on the specificity and use of GSK2606414 and GSK2656157.
AB  - Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes a
      state of cellular stress known as ER stress. The cells respond to ER stress by
      activating the unfolded protein response (UPR), a signaling network emerging from
      the ER-anchored receptors IRE1alpha, PERK and ATF6. The UPR aims at restoring ER
      protein-folding homeostasis, but turns into a toxic signal when the stress is too
      severe or prolonged. Recent studies have demonstrated links between the UPR and
      inflammation. Consequently, small molecule inhibitors of IRE1alpha and PERK have
      become attractive tools for the potential therapeutic manipulation of the UPR in
      inflammatory conditions. TNF is a master pro-inflammatory cytokine that drives
      inflammation either directly by promoting gene activation, or indirectly by
      inducing RIPK1 kinase-dependent cell death, in the form of apoptosis or
      necroptosis. To evaluate the potential contribution of the UPR to TNF-induced
      cell death, we tested the effects of two commonly used PERK inhibitors,
      GSK2606414 and GSK2656157. Surprisingly, we observed that both compounds
      completely repressed TNF-mediated RIPK1 kinase-dependent death, but found that
      this effect was independent of PERK inactivation. Indeed, these two compounds
      turned out to be direct RIPK1 inhibitors, with comparable potency to the recently
      developed RIPK1 inhibitor GSK'963 (about 100 times more potent than NEC-1s).
      Importantly, these compounds completely inhibited TNF-mediated RIPK1-dependent
      cell death at a concentration that did not affect PERK activity in cells. In
      vivo, GSK2656157 administration protected mice from lethal doses of TNF
      independently of PERK inhibition and as efficiently as GSK'963. Together, our
      results not only report on new and very potent RIPK1 inhibitors but also
      highlight the risk of misinterpretation when using these two PERK inhibitors in
      the context of ER stress, cell death and inflammation.

PMID- 28452997
TI  - Not just browsing: an animal that grazes phyllosphere microbes facilitates
      community heterogeneity.
AB  - Although grazers have long been recognized as top-down architects of plant
      communities, animal roles in determining microbial community composition have
      seldom been examined, particularly in aboveground systems. To determine the
      extent to which an animal can shape microbial communities, we conducted a
      controlled mesocosm study in situ to see if introducing mycophageous tree snails
      changed phyllosphere fungal community composition relative to matched control
      mesocosms. Fungal community composition and change was determined by Illumina
      sequencing of DNA collected from leaf surfaces before snails were introduced,
      daily for 3 days and weekly for 6 weeks thereafter. Scanning electron microscopy
      was used to confirm that grazing had occurred, and we recorded 3.5 times more
      cover of fungal hyphae in control mesocosms compared with those containing
      snails. Snails do not appear to vector novel microbes and despite grazing, a
      significant proportion of the initial leaf phyllosphere persisted in the
      mesocosms. Within-mesocosm diversities of fungi were similar regardless of
      whether or not snails were added. The greatest differences between the snail
      treated and control mesocosms was that grazed mesocosms showed greater
      infiltration of microbes that were not sampled when the experiment commenced and
      that the variance in fungal community composition (beta diversity) was greater
      between leaves in snail-treated mesocosms indicating increased community
      heterogeneity and ecosystem fragmentation.

PMID- 28452998
TI  - Plant cell growth: Cellulose caught slipping.

PMID- 28452999
TI  - CAD/CAM Ceramic Overlays to Restore Reduced Vertical Dimension of Occlusion
      Resulting from Worn Dentitions: A Case History Report.
AB  - Two patients with a reduced vertical dimension of occlusion as a result of teeth
      wear were prescribed ceramic overlays. Their 2-year follow-up suggested good
      adaptation to the recovered muscle support without associated symptoms or adverse
      alterations in the restorations.

PMID- 28453000
TI  - Psychopathologic Profiles of TMD Patients with Different Pain Locations.
AB  - PURPOSE: The aim of this study was to examine whether psychopathologic profile is
      related to the location of pain in temporomandibular disorder (TMD) patients with
      myofascial and/or temporomandibular joint pain. MATERIALS AND METHODS: A total of
      75 painful TMD patients (39 women and 36 men) participated in the study.
      Participants were divided into three groups (myogenous, arthrogenous, and mixed)
      using the Research Diagnostic Criteria for TMD (RDC/TMD) Axis I guidelines for
      assessment of TMD signs and symptoms. Three psychometric instruments were used to
      assess the psychopathologic profile of the TMD subgroups. Patients' state and
      trait anxiety were assessed using the State-Trait Anxiety Inventory (STAI-S, STAI
      T), depression was measured with the Center for Epidemiological Studies
      Depression Scale (CES-D), and psychosocial functioning was evaluated using the
      Global Disability Scale (Glo.Di.S). The three TMD groups were compared with
      Kruskal-Wallis test followed by pairwise Mann-Whitney tests relative to the
      psychometric scores. Statistical analyses were performed with SPSS 15.0 software.
      RESULTS: No significant differences were detected among the different TMD groups
      in the three psychometric scales; STAI-T, CES-D, Glo.Di.S (P > .05). When the
      psychometric scale of state anxiety (STAI-S) was considered, significant
      differences were revealed between the myogenous and the arthrogenous pain groups
      (P = .008) and also between the mixed and the arthrogenous groups (P < .001).
      CONCLUSION: These findings suggest that the psychopathologic profile is not
      related to the location of pain in TMD patients. However, anxiety was found to be
      higher in TMD patients with myogenous pain alone or combined with arthrogenous
      pain compared to those with only arthrogenous pain.

PMID- 28453001
TI  - Mechanical Complications Associated with Angled Screw Channel Restorations.
AB  - The aim of this study was to identify mechanical complications associated with
      Nobel Biocare's angled screw channel (ASC) restorations following provision of
      the definitive crown. All ASC restorations provided between 1 January 2014 and 19
      January 2016 were identified. Patients' clinical records were reviewed for
      demographic details, implant characteristics, occlusal considerations, and
      complications. A total of 84 implants placed in 60 patients were included. Three
      patients (4%) returned with mechanical complications, but the majority (n = 81;
      96%) had no recorded complications. Long-term follow up is needed, but ASC
      restorations appear to offer a reliable and retrievable alternative to cement
      retained restorations.

PMID- 28453002
TI  - Fabricating a Maxillary Obturator Using an Intraoral Digital Impression: A Case
      History Report.
AB  - Digital impressions can be a useful option that reduces patient discomfort and
      simplifies clinical procedures such as accurate impression recordings. In this
      report, a patient with a partial maxillectomy was managed with a metal frame
      fabricated from a digital impression through an intraoral scanner. The final
      impression employed the altered cast technique for the fabrication of the
      obturator.

PMID- 28453003
TI  - CAD/CAM-Fabricated Nonmetal Clasp Denture: In Vitro Pilot Study.
AB  - PURPOSE: The purpose of this study was to fabricate a prototype nonmetal clasp
      denture using computer-aided design/computer-assisted manufacture (CAD/CAM)
      technology. MATERIALS AND METHODS: A partially edentulous mandibular working cast
      was scanned using an optical scanner. A sectional denture separated by two parts
      was designed on the scanned cast. These parts were milled and combined, and
      adhered using an adhesive luting agent. RESULTS: The completed denture was
      delivered on the working cast and provided an excellent level of fitness.
      CONCLUSION: A prototype nonmetal clasp denture could be fabricated using CAD/CAM
      technology.

PMID- 28453004
TI  - Implant Utilization and Time to Prosthetic Rehabilitation in Conventional and
      Advanced Fibular Free Flap Reconstruction of the Maxilla and Mandible.
AB  - PURPOSE: Precisely designed jaw reconstruction rehabilitation (JRR) is important
      to the integrity of the jaw structure and oral functions. Advanced three
      dimensional (3D) digital surgical design and simulation (SDS) techniques have the
      potential to reduce time to reconstructive and dental treatment completion,
      thereby promoting early functional oral rehabilitation. This study investigated
      the use of SDS in JRR procedures. MATERIALS AND METHODS: A retrospective chart
      review was conducted on adult head and neck tumor (HNT) participants who
      completed JRR treatment with a fibular free flap (FFF) reconstruction. Two
      treatment approaches, advanced 3D SDS technique (with-SDS) and conventional,
      nondigitally planned technique (without-SDS), included the use of osseointegrated
      implants. Data were collected from adult patients treated between January 2000
      and March 2014 at the Institute for Reconstructive Sciences in Medicine (iRSM).
      Participants were excluded if they underwent a bone-containing augmentation to
      the FFF reconstruction. The without-SDS group underwent a conventional, nonguided
      FFF reconstruction followed by nonguided implant placement. The with-SDS group
      underwent a guided FFF reconstruction with guided implant placement during the
      reconstructive surgery. The outcome measures included implant utilization (ratio
      of implants placed to connected) and time to prosthetic connection after FFF
      reconstruction. Mann-Whitney U test was used to analyze the data. RESULTS: The
      digital SDS technique (with-SDS) group completed prosthetic treatment with a
      significantly higher utilization of implants as well as a significantly shorter
      time to prosthetic delivery. CONCLUSION: SDS allows an interdisciplinary
      treatment team to work together to create a virtual plan that leads to greater
      efficiency in patient treatment time and utilization of dental implants.

PMID- 28453005
TI  - A p-nitroaniline redox-active solid-state electrolyte for battery-like
      electrochemical capacitive energy storage combined with an asymmetric
      supercapacitor based on metal oxide functionalized beta-polytype porous silicon
      carbide electrodes.
AB  - A unique redox active flexible solid-state asymmetric supercapacitor with ultra
      high capacitance and energy density was fabricated using a composite comprising
      MgCo2O4 nanoneedles and micro and mesoporous silicon carbide flakes (SiCF)
      (SiCF/MgCo2O4) as the positive electrode material. Due to the synergistic effect
      of the two materials, this hybrid electrode has a high specific capacitance of
      516.7 F g-1 at a scan rate of 5 mV s-1 in a 1 M KOH aqueous electrolyte. To
      obtain a reasonable matching of positive and negative electrode pairs, a
      composite of Fe3O4 nanoparticles and SiCF (SiCF/Fe3O4) was synthesized for use as
      a negative electrode material, which shows a high capacitance of 423.2 F g-1 at a
      scan rate of 5 mV s-1. Therefore, by pairing the SiCF/MgCo2O4 positive electrode
      and the SiCF/Fe3O4 negative electrode with a redox active quasi-solid-state PVA
      KOH-p-nitroaniline (PVA-KOH-PNA) gel electrolyte, a novel solid-state asymmetric
      supercapacitor device was assembled. Because of the synergistic effect between
      the highly porous SiCF and the vigorous redox-reaction of metal oxides, the
      hybrid nanostructure electrodes exhibited outstanding charge storage and
      transport. In addition, the redox active PVA-KOH-PNA electrolyte adds additional
      pseudocapacitance, which arises from the nitro-reduction and oxidation and
      reduction process of the reduction product of p-phenylenediamine, resulting in an
      enhancement of the capacitance (a specific capacitance of 161.77 F g-1 at a scan
      rate of 5 mV s-1) and energy density (maximum energy density of 72.79 Wh kg-1 at
      a power density of 727.96 W kg-1).

PMID- 28453006
TI  - Two cations, two mechanisms: interactions of sodium and calcium with zwitterionic
      lipid membranes.
AB  - Adsorption of metal cations onto a cellular membrane changes its properties, such
      as interactions with charged moieties or the propensity for membrane fusion. It
      is, however, unclear whether cells can regulate ion adsorption and the related
      functions via locally adjusting their membrane composition. We employed
      fluorescence techniques and computer simulations to determine how the presence of
      cholesterol-a key molecule inducing membrane heterogeneity-affects the adsorption
      of sodium and calcium onto zwitterionic phosphatidylcholine bilayers. We found
      that the transient adsorption of sodium is dependent on the number of
      phosphatidylcholine head groups, while the strong surface binding of calcium is
      determined by the available surface area of the membrane. Cholesterol thus does
      not affect sodium adsorption and only plays an indirect role in modulating the
      adsorption of calcium by increasing the total surface area of the membrane. These
      observations also indicate how lateral lipid heterogeneity can regulate various
      ion-induced processes including adsorption of peripheral proteins, nanoparticles,
      and other molecules onto membranes.

PMID- 28453007
TI  - Ligand influence in Li-ion battery hybrid active materials: Ni
      methylenediphosphonate vs. Ni dimethylamino methylenediphosphonate.
AB  - The influence of a ligand on the structural, morphological and electrochemical
      properties of organic-inorganic hybrid nickel diphosphonates was assessed using
      Ni methylenediphosphonate (NiMeDP) and Ni dimethylamino methylenediphosphonate
      (NiDMAMDP) as model electrode materials.

PMID- 28453008
TI  - Enhanced base-catalyzed activity and structural stability of nitrogen-doped
      carbon modified MgO-MgFe2O4 magnetic composites as catalysts for
      transesterification of tributyrin.
AB  - In this work, nitrogen-doped carbon modified MgO-MgFe2O4 (CN-MgFeO) magnetic
      composites were synthesized by a facile thermal decomposition of Mg-Fe layered
      double hydroxide (MgFe-LDH) and cyanamide mixture precursors. A series of
      comprehensive characterization studies including powder X-ray diffraction,
      transmission electron microscopy, Fourier transform infrared of CO2 adsorption,
      CO2-temperature programmed desorption, and X-ray photoelectron spectroscopy
      indicated that the introduction of cyanamide could finely tune the surface
      basicity of the resulting CN-MgFeO composites, especially surface strong Lewis
      basicity. Compared with CN-free MgFeO, the as-fabricated CN-MgFeO catalysts
      showed higher activity in the liquid-phase transesterification of tributyrin with
      methanol. Particularly, the CN-MgFeO composite prepared at a cyanamide/Mg molar
      ratio of 1.5 in the synthesis mixture gave a highest methylbutyrate yield of 80%
      after a reaction for 20 min. The high catalytic performance was attributable to
      the presence of a large amount of strong Lewis basic sites originating from
      highly dispersed basic MgO-MgFe2O4 mixed metal oxides and CN component in the
      composite. What is more, such a cost-effective CN-MgFeO catalyst had the
      advantages of intrinsic magnetic properties and an excellent structural
      stability. We expect that they may have potential practical applications in the
      field of industrial production of biodiesels.

PMID- 28453009
TI  - Phosphido complexes derived from 1,1'-ferrocenediyl-bridged secondary
      diphosphines.
AB  - This paper focuses on ferrocene-based secondary diphosphines of the type [Fe{eta5
      C5H4(PHR)}2] with P-substituents of distinctly different steric and electronic
      properties, namely methyl, neopentyl (Np), tert-butyl, phenyl and 3,5
      bis(trifluoromethyl)phenyl (XyF). The reaction of [Fe{eta5-C5H4(PHPh)}2] (H21a)
      and [Fe{eta5-C5H4(PHt-Bu)}2] (H21b) with n-BuLi in the presence of TMEDA afforded
      lithium diphosphides of the type [Li2(MU-1)(TMEDA)2], which contain a cyclic non
      planar Li2P2 core. The analogous reactions of [Fe{eta5-C5H4(PHMe)}2] (H21c) and
      [Fe{eta5-C5H4(PHNp)}2] (H21d) furnished dimeric aggregates exhibiting a ladder
      type Li4P4 motif, viz. [Li4(MU-1c)2(TMEDA)3] and [Li2(MU-1d)(TMEDA)]2. H21e (R =
      XyF) did not afford a stable lithium diphosphide. A Bronsted metathesis with
      Zr(NMe2)4 was possible with the aryl-substituted compounds H21a and H21e, leading
      to products of the type [{Zr(NMe2)3}2(MU-1)]. In contrast, the alkyl-substituted
      congeners H21b-H21d were inert towards Zr(NMe2)4. The reaction of [Fe{eta5
      C5H4(PHR)}2] with nickelocene afforded intractable mixtures of numerous products
      in the case of H21c and H21e. In the other three cases, compounds of the type
      [(NiCp)2(MU-1)] were isolated. For H21b and H21d a two-stepped reaction via a
      phosphino-phosphido intermediate of the type [NiCp(H1)] was observed, which could
      be isolated and fully characterised in the case of [NiCp(H1b)].

PMID- 28453010
TI  - Effect of nucleobase change on cytosine deamination through DNA photo-cross
      linking reaction via 3-cyanovinylcarbazole nucleoside.
AB  - Photo-chemical deamination of cytosine using 3-cyanovinylcarbazole nucleoside
      (CNVK) mediated photo-cross-linking is a technique for site-directed mutagenesis.
      Using this technique in vivo requires the elimination of a high-temperature
      incubation step; instead, incubation should be carried out under physiological
      conditions. To improve the reactivity of CNVK mediated photo-cross-link induced
      deamination of cytosine under physiological conditions, an evaluation of base
      pairing in cytosine was carried out with respect to its deamination. Guanine was
      replaced with 4 different counter bases (inosine, 2-aminopurine, 5-nitroindole,
      and nebularine), showing distinct hydrogen bonding patterns with target cytosine,
      which was incorporated at the -1 position with respect to CNVK in the CNVK
      modified photo-responsive oligodeoxyribonucleotides to ascertain the role of
      hydrogen bonding in deamination under physiological conditions. Among the counter
      bases, inosine showed the highest acceleration towards the photo-induced
      deamination reaction.

PMID- 28453011
TI  - A Co-based single-molecule magnet confined in a barium phosphate apatite matrix
      with a high energy barrier for magnetization relaxation.
AB  - An apatite-type barium phosphate with a high content of cobalt ions in the
      trigonal channels features slow relaxation of magnetization with an energy
      barrier Ueff of up to 387 cm-1, which is well above the values for all so far
      known d-metal based single-molecule magnets (SMMs).

PMID- 28453012
TI  - Ab initio assessment of Bi1-xRExCuOS (RE = La, Gd, Y, Lu) solid solutions as a
      semiconductor for photochemical water splitting.
AB  - The investigation of the BiCuOCh (Ch = S, Se and Te) semiconductor family for
      thermoelectric or photovoltaic materials is a topic of increasing research
      interest. These materials can also be considered for photochemical water
      splitting if one representative having a bandgap, Eg, at around 2 eV can be
      developed. With this aim, we simulated the solid solutions Bi1-xRExCuOS (RE = Y,
      La, Gd and Lu) from pure BiCuOS (Eg ~ 1.1 eV) to pure RECuOS compositions (Eg ~
      2.9 eV) by DFT calculations based on the HSE06 range-separated hybrid functional
      with the inclusion of spin-orbit coupling. Starting from the thermodynamic
      stability of the solid solution, several properties were computed for each system
      including bandgaps, dielectric constants, effective masses and exciton binding
      energies. We discussed the variation of these properties based on the relative
      organization of Bi and RE atoms in their common sublattice to offer a physical
      understanding of the influence of the RE doping of BiCuOS. Some compositions were
      found to give appropriate properties for water splitting applications.
      Furthermore, we found that at low RE fractions the transport properties of BiCuOS
      are improved that can find applications beyond water splitting.

PMID- 28453013
TI  - Lanthanide coordination polymer nanoparticles as a turn-on fluorescence sensing
      platform for simultaneous detection of histidine and cysteine.
AB  - In this work, we propose a strategy for the fluorescence assay of histidine (His)
      and cysteine (Cys) by using lanthanide coordination polymer nanoparticles (Ln
      CPN) as a fluorescent probe. The Ln-CPN were prepared by self-assembly of
      adenosine monophosphate (AMP) with Tb3+, i.e. AMP-Tb. The nonluminescent AMP-Tb
      could be efficiently sensitized by 5-sulfosalicylic acid (SSA). The fluorescence
      of AMP-Tb-SSA can be remarkably quenched by Cu2+, and that of the resulting
      Cu/SSA/AMP-Tb can be significantly enhanced by His and Cys. Thus, a specific
      fluorescence "turn-on" assay for His and Cys was developed by using Cu/SSA/AMP-Tb
      as a sensing platform. The enhanced fluorescence intensity was proportional to
      the His and Cys concentration in the range from 0.2 to 150 MUM and 0.5 to 200
      MUM, respectively, with the detection limits of 70 nM and 100 nM. Additionally,
      taking advantage of a masking agent for His, the differentiation of His from Cys
      was achieved in our system. Furthermore, the protocol can also work well for
      analyzing His and Cys in practical plasma samples with recovery in the range of
      100.3-104.1%.

PMID- 28453014
TI  - Revisiting the definition of local hardness and hardness kernel.
AB  - An analysis of the hardness kernel and local hardness is performed to propose new
      definitions for these quantities that follow a similar pattern to the one that
      characterizes the quantities associated with softness, that is, we have derived
      new definitions for which the integral of the hardness kernel over the whole
      space of one of the variables leads to local hardness, and the integral of local
      hardness over the whole space leads to global hardness. A basic aspect of the
      present approach is that global hardness keeps its identity as the second
      derivative of energy with respect to the number of electrons. Local hardness thus
      obtained depends on the first and second derivatives of energy and electron
      density with respect to the number of electrons. When these derivatives are
      approximated by a smooth quadratic interpolation of energy, the expression for
      local hardness reduces to the one intuitively proposed by Meneses, Tiznado,
      Contreras and Fuentealba. However, when one combines the first directional
      derivatives with smooth second derivatives one finds additional terms that allow
      one to differentiate local hardness for electrophilic attack from the one for
      nucleophilic attack. Numerical results related to electrophilic attacks on
      substituted pyridines, substituted benzenes and substituted ethenes are presented
      to show the overall performance of the new definition.

PMID- 28453015
TI  - The mechanism of the Ser-(cis)Ser-Lys catalytic triad of peptide amidases.
AB  - In this paper, we report a theoretical investigation of the catalytic mechanism
      of peptide amidases that involve a Ser-(cis)Ser-Lys catalytic triad. Previous
      suggestions propose that these enzymes should follow a distinct catalytic
      mechanism from the one that is present in the classic Ser-His-Asp catalytic
      triad. The theoretical and computational results obtained in this work indicate
      the opposite idea, showing that both mechanisms are very similar and only few
      differences are observed between both reactions. The results reveal that the
      different alignment of the Ser-(cis)Ser-Lys catalytic triad in relation to the
      classical Ser-His-Asp triad may provide a better stabilisation of the reaction
      intermediates, and therefore make these enzymes catalytically more efficient. The
      catalytic mechanism has been determined at the M06-2X/6-311++G**//B3LYP/6-31G*
      level of theory and requires five sequential steps instead of the two that are
      generally proposed: (i) nucleophilic attack of serine on the carbonyl group of
      the substrate, forming the first tetrahedral intermediate, (ii) formation of an
      acyl-enzyme complex, (ii) release of an ammonia product, (iv) nucleophilic attack
      of a water molecule forming the second tetrahedral intermediate, and (iv) the
      release of the product of the reaction, the carboxylic acid. The computational
      results suggest that the rate-limiting step is the first one that requires an
      activation free energy of 15.93 kcal mol-1. This result agrees very well with the
      available experimental data that predict a reaction rate of 2200 s-1, which
      corresponds to a free energy barrier of 14 kcal mol-1.

PMID- 28453016
TI  - The atmospheric oxidation of CH3OOH by the OH radical: the effect of water vapor.
AB  - The atmospheric oxidation of methyl hydroperoxide by the hydroxyl radical has
      been investigated employing high level theoretical methods. This reaction is
      important in the chemistry of the troposphere because these species contribute to
      the oxidizing capacity of the atmosphere and therefore we have studied the bare
      reaction and the effect of the relative humidity as well. In both cases the
      reaction can proceed either by abstraction of the terminal hydrogen atom of the
      OH group, producing CH3O2 + H2O, or by abstraction of one hydrogen atom of the
      CH3 group, forming H2CO + OH + H2O. We have employed BH&HLYP, QCISD and CCSD(T)
      theoretical methods along with 6-311+G(2df,2p), aug-cc-pVTZ, aug-cc-pVQZ and CBS
      basis sets to investigate the reaction mechanism, and conventional and
      variational transition state theory to study the kinetics of the reaction. For
      the bare reaction we have computed at room temperature, a rate constant of 3.59 *
      10-12 cm3 molecule-1 s-1 for the formation of CH3O2 + H2O and of 1.68 * 10-12 cm3
      molecule-1 s-1 for the production of H2CO + OH + H2O, with branching ratios of
      68% and 32% respectively. Water vapor enhances the rate constant for the
      formation of CH3O2 + H2O between 2 and 19%, depending on the temperature and
      relative humidity, whereas the rate constant for the production of H2CO + OH +
      H2O is enhanced between 0.3 and 5% by the effect of water vapor under the same
      conditions, which means that the branching ratio for the formation of CH3O2 + H2O
      is increased up to 2.5%.

PMID- 28453017
TI  - Femtosecond time-resolved photoelectron spectroscopy of the benzyl radical.
AB  - We present a joint experimental and computational study of the nonradiative
      deactivation of the benzyl radical, C7H7, after UV excitation. Femtosecond time
      resolved photoelectron imaging was applied to investigate the photodynamics of
      the radical. The experiments were accompanied by excited state dynamics
      simulations using surface hopping. Benzyl has been excited at 265 nm into the D
      band (pipi*) and the dynamics was probed using probe wavelengths of 398 nm or 798
      nm. At a probe wavelength of 398 nm a single time constant of around 70-80 fs was
      observed. When the dynamics was probed at 798 nm, a second time constant tau2 =
      1.5 ps was visible, which can be attributed to further non-radiative deactivation
      to the lower-lying D1/D2 states.

PMID- 28453018
TI  - Confinement-driven organization of a histone-complexed DNA molecule in a dense
      array of nanoposts.
AB  - The first step in the controlled storage of lengthy DNA molecules is to keep DNA
      molecules separated while integrated in micrometer-sized space. Herein, we
      present hybrid Monte Carlo simulations of a histone-complexed DNA (hcDNA)
      molecule confined in a dense array of nanoposts. Depending on the nanopost
      dimension, a single, 8.7 kilobase pair hcDNA molecule was either localized and
      elongated in a single inter-post space surrounded by four nanoposts or spread
      over several inter-post spaces through passages between two neighboring
      nanoposts. The conformational change of a hcDNA molecule is interpreted in terms
      of competitive effects of confinements in the inter-post and passage spaces. We
      propose that, by elaborately designing nanopost arrays, the competitive
      confinement effects can be adjusted such that each hcDNA molecule is localized in
      a single inter-post space, and thereby multiple hcDNA molecules can be physically
      separated from each other while stored together in the nanopost array.

PMID- 28453019
TI  - Site accessibility tailors DNA cleavage by restriction enzymes in DNA confined
      monolayers.
AB  - Density-tunable nanografted monolayers (NAMs) of short oligonucleotide sequences
      on gold surfaces show novel properties that make them suitable for advanced
      biosensing applications, and in particular to study the effects of crowding and
      confinement on biomolecular interactions. Here, combining atomic force microscopy
      nanolithography, topography measurements and coarse-grained molecular dynamics
      simulations, we investigated restriction enzyme reaction mechanisms within
      confined DNA brushes highlighting the role played by the DNA sequence
      conformation and restriction site position along the chain, respectively, in
      determining the accessibility of the enzyme, and its consequent cleavage
      efficiency.

PMID- 28453020
TI  - Graphene oxide/black phosphorus nanoflake aerogels with robust thermo-stability
      and significantly enhanced photothermal properties in air.
AB  - Here we report a new kind of three-dimensional (3D) hybrid aerogels, based on
      graphene oxide (GO) and black phosphorus nanoflakes (BPNFs), for the first time.
      Our results demonstrate that the as-prepared GO/BPNF hybrid aerogels exhibited
      significantly enhanced photothermal as well as electrical properties of GO
      aerogels due to the addition of BP. Moreover, they also possessed excellent
      photothermal stability under ambient conditions without any protection, which can
      be ascribed to the coverage of BPNFs with GO nanosheets in these aerogels. This
      exceptional photothermal property along with robust stability renders GO/BPNF
      aerogels with promising bio-related applications, such as photothermal therapy
      for cancer treatment.

PMID- 28453021
TI  - Binary twinned-icosahedral [B21H18]- interacts with cyclodextrins as a precedent
      for its complexation with other organic motifs.
AB  - The weakly coordinating binary macropolyhedral anion closo,closo-[B21H18]- (B21;
      D3h symmetry) has been synthesized using a simplified strategy compared to that
      in the literature. While gas-phase complexes of B21 with beta- and gamma
      cyclodextrin (CD) were detected using ESI FT-ICR spectrometric measurements,
      alpha-CD did not bind to the B21 guest. This spectroscopic evidence has been
      interpreted using quantum-chemical computations, showing that beta- and gamma-CD
      are able to interact with B21 due to their larger cavities, in contrast to the
      smaller alpha-CD. The hydridic B-H vectors of the B21 anion interact with K+
      counterions and, via dihydrogen bonding, also with the partially positively
      charged hydrogens of the CD sugar units in the modeled beta- and gamma-CD
      complexes. In summary, it has been shown by combined spectrometric/computational
      analysis that macropolyhedral boron hydride anions with two counterions can form
      stable complexes with beta- and gamma-CD in the gas phase, offering a new
      perspective for the future investigation of this remarkable anion in the areas of
      supramolecular and medicinal chemistries.

PMID- 28453022
TI  - [Evolution of epidemiological and clinical characteristics of adults patients
      belonging to the national program at start of antiretroviral therapy in the
      Chilean AIDS Cohort, 2001-2015].
AB  - BACKGROUND: Chilean AIDS Cohort is the oldest and extensive in Latin America and
      one of most numerous and with longer follow up time to international level.
      Records information from 14,873 patients out of approximately 22,000 in
      antiretroviral therapy in the public system and its results have allowed to know
      the national reality and have contributed to the adoption of public policies.
      AIM: To describe the demographic, clinical and immunological characteristics of
      patients who have started ART in Chile and its evolution over the past 15 years.
      PATIENTS AND METHODS: The cases were stratified by five-year periods: 2001-2005,
      2006-2010 and 2011-2015. The data analysis included calculating proportions,
      their respective confidence intervals 95% and X2 test for significance analysis
      was applied. RESULTS: 17.4% of patients starting ART are women and the proportion
      has remained relatively constant. The highest proportion of new HIV cases are 30
      and 39 years old, nevertheless the layer of 15-29 years demonstrates a
      significant increase from 21.7 to 36.4% in 2011-2015 especially in men. 12.1% of
      new cases are older than 50 years old with a stable trend over time; however,
      women over 50 have increased from 11.0 to 15.6%. Antiretroviral therapy
      initiation with CD4+ T lymphocytes less than 200 cells/mm3 has decreased from
      79.7 to 42.4% and in stage C from 45.4 to 22.6%. Late presentation to
      antiretroviral therapy is higher in men but this gap has narrowed in the last
      five years. Pneumocystis jiroveci, wasting syndrome, tuberculosis, Kaposi's
      sarcoma and esophageal candidiasis are the most common opportunistic diseases
      without significant changes in the three-year periods analyzed. In the last five
      years, 15.5% of opportunistic diseases occurs in patients with CD4+ TL > 200
      cells/mm3. DISCUSSION: Despite the limitations of observational studies present
      report describes the characteristics and evolution of the epidemics in Chile in
      the last 15 years. The infection occurs at younger ages in men, whereas in women
      there is an increase over 50 years old. Despite advances in treatment access have
      reduced late presentation to therapy, important challenges remain to achieve more
      timely initiation of antiretroviral therapy in accordance with WHO 90-90-90
      goals.

PMID- 28453023
TI  - [HIV/AIDS infection in children and adolescents: Chilean cohort 1987-2014].
AB  - The present document describes the Cohort of HIV/AIDS children detected in Chile
      from 1987 to August 2014 and the effectiveness of the Protocol for Prevention of
      Vertical Transmission (PPVT) of HIV infection. Of the 375 HIV infected children
      enrolled since 1987 to August 2014, 245 of them are still in pediatric control.
      From the analysis of the Cohort is inferred that: a) it has observed an
      improvement in the detection of the HIV infected child, in number and precocious
      time; b) the majority of these children continue to be detected by clinic
      symptoms and signs (mainly unspecific and infectious manifestations); c) the ARVT
      use has meant a clinic and immunologic improvement with diminution of the
      infections, principally opportunistic infections, with a better life quality, a
      prolongation of survival and a diminution of lethality; d) as more survival has
      been produced, cancer has begun to be detected, a very infrequent complication
      observed in them before the ARVT use. The PPVT started in 1995, and was
      reinforced in 2005 with the "Joint Norm of HIV and Syphilis Vertical Transmission
      Prevention" (MINSAL), both have meant a diminution of the HIV vertical
      transmission from > 35% (before 1995) to < 2% nowadays in the mother-child
      binomial; also have permitted a second generation of HIV exposed children born
      without infection. In spite this PPVT, still HIV infected child continue to be
      detected which imply failures in some points of the health system.

PMID- 28453024
TI  - [Late diagnosis and advanced disease of HIV in adult patients from a Peruvian
      social security hospital].
AB  - BACKGROUND: The delayed HIV diagnosis with CD4 count is a public health problem.
      OBJECTIVE: To determinate the frequency and the factors associated with a late
      diagnosis (LD) and to an advanced disease (AD) of HIV infection in patients from
      a Peruvian hospital. MATERIALS AND METHODS: Analytic and transversal study of
      secondary data from adult's patients diagnostic with HIV during the period 1999
      2012. RESULTS AND CONCLUSIONS: From 1,714 patients, 82.6% (1416) had LD, and
      64.5% (1106) were diagnostic with AD. Were associated with them: being of male
      sex (LD: 17% and AD: 28%; p < 0.001), have between 41-60 years (LD: 9% and AD:
      15%; p < 0.001), have more than 60 years old (LD: 14% and AD: 23%; p < 0.003),
      being bisexual (LD: 18% and AD: 43%; p < 0.001), drugs abusers (LD: 24% and AD:
      64%; p < 0.001). Being heterosexual was associated with less frequency (LD: 12%
      and AD: 19%; p < 0.001). The frequency of LD and AD of HIV are high and factors
      associated with them were male sex, being 40 years old or more, and belonging to
      sexually risk groups (homosexuals and bisexuals) and drugs abusers.

PMID- 28453025
TI  - [Oral lesions associated with human immunodeficiency virus disease in adult
      patients, a clinical perspective].
AB  - Among the clinical manifestations which may occur in HIV/AIDS patients, oral
      lesions are relevant because there are easily accessible and usually the
      diagnosis is made through clinical features. Some oral manifestations are
      strongly related with HIV/AIDS patients indicating infection and progression to
      AIDS and also allow monitoring the success or failure of using antiretroviral
      therapy. The massive introduction of antiretroviral therapy has changed the
      morbidity and mortality, frequency, type of clinical manifestation and the timing
      of the classic opportunistic complications. The aim of this review is to provide
      an updated of the classical clinical features of the most frequent and relevant
      HIV/AIDS oral manifestations, considering the fundamental clinical features for
      their diagnosis.

PMID- 28453026
TI  - [The clinical relevance of drug interactions in patients with human
      immunodeficiency virus infection: update 2009-2014].
AB  - OBJECTIVE: To update information about drug interactions in patients with
      HIV/AIDS. METHODS: Comprehensive literature review in MEDLINE/PubMed database
      from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral
      agents and drug interactions or herb-drug interactions or food-drug interactions.
      Publications with drug interactions in humans, in English or Spanish, and with
      full text were retrieved. Additionally, citation lists from identified articles
      were reviewed. The study inclusion was assessed by three independent researchers
      and by consensus among them when was necessary. Clinical relevance of drug
      interaction was grouped into four levels according to seriously and probability
      of occurrence. RESULTS: Global, 546 different references were retrieved and 243
      were selected. In addition 11 further manuscripts were identified in the
      references of the included articles. Overall, 935 pairs of drug interactions were
      identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67
      by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%)
      were classified as levels 1 or 2. CONCLUSIONS: The most clinically relevant
      antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly
      induction or enzyme inhibition, according to previous reviews, the protease
      inhibitors remain as the antiretrovirals with the highest number of clinical
      relevant interactions.

PMID- 28453027
TI  - [Prevalence of potential drug-drug interactions involving antiretroviral drugs in
      Buenos Aires, Argentina].
AB  - INTRODUCTION: Antiretroviral agents (ARVs) have a high potential for drug
      interactions. However, the prevalence and risk factors for clinically significant
      drug-drug interactions (CSDDIs) with ARVs from Latin American countries is
      unknown. AIM: To evaluate the prevalence and risk factors for CSDDIs in HIV
      outpatients attending at two centers in Buenos Aires, Argentina. METHODS:
      Descriptive cross-sectional study (september to november 2012). HIV-1 infected
      patients under ARV treatment at the time of the study were randomly assessed for
      concomitant medication. CSDDIs were screened using the University of Liverpool
      Drug Interactions Program (www.hiv-druginteractions.org). RESULTS: A total of 217
      patients were included. Male sex: 64% (CI 95: 57-70). Median age (IQR): 41 (36
      48). Presence of comorbidities: 19%. ARV regimen: NNRTI-based: 48%, PI-based: 50%
      and NNRTI plus PI: 2%. Median of CD4 T-cell count (IQR): 402 cells/mL (235-588).
      Viral load < 50 copies/mL: 78%. Overall, 64% (CI 95: 57-70) of patients had > 1
      co-medication of whom a 49% had at least one CSDDI. Two patients had a CSDDI
      between ARVs. The most frequent co-medications observed were antimicrobial (40%),
      cardiovascular (25%) and gastrointestinal agents (22%). In the multivariate
      analysis the number of co-medications and use of CNS agents were associated with
      the presence of CSDDIs. CONCLUSIONS: Co-medications and CSDDIs were common in our
      setting. In this context, training of HIV physicians in drug interactions is of
      major importance for adequate management of these patients.

PMID- 28453028
TI  - [Antiretroviral therapy containing raltegravir in HIV-infected pregnant women:
      Systematic review].
AB  - INTRODUCTION: The risk of mother to child transmission (MTCT) of HIV increases in
      pregnant women diagnosed late in pregnancy. Some experts suggest that the use of
      raltegravir (RAL), as part of the antiretroviral treatment in these pregnant
      women, could reduce the risk of MTCT, since RAL can quickly decrease the viral
      load. OBJECTIVE: To evaluate the available scientific information on the efficacy
      and safety of RAL, during the third trimester of pregnancy, in reducing MTCT of
      HIV. METHODS: We conducted a systematic review of the literature. The following
      databases were consulted: MEDLINE, Tripdatabase, Cochrane, Lilacs and Web of
      Science. We included systematic reviews, clinical trials, observational studies
      or case reports. The search was not filtered by language. RESULTS: Fourteen
      studies met the inclusion criteria. Selected studies were case reports or case
      series. We included, in total, 44 pregnancies (with 45 live births). A case of
      TMI of HIV was reported. Eight studies reported adverse events, of which four
      cases can be attributed to the use of RAL. CONCLUSION: There is insufficient
      evidence on the efficacy and safety of RAL to decrease the risk of MTCT in HIV
      pregnant women who present in the last trimester of pregnancy.

PMID- 28453029
TI  - Medical entomology, a necessity.

PMID- 28453030
TI  - [Demographic, social, physical and mental factors associated with functional
      capacity in the elderly, Antioquia, Colombia, 2012].
AB  - Objective To describe the demographic, social, physical and mental health factors
      associated with the functional capacity of older adults in the Department of
      Antioquia in 2012. Materials and Methods A descriptive study with the records of
      4 248 adults aged 60 years or more as the population, surveyed in the Department
      of Antioquia, in 2012. They were asked about their functional capacity through a
      Katz survey consisting of 6 items. With the independent variables, frequency
      measurements were calculated, along with crude and adjusted prevalence ratios
      (PR) with their respective 95 % CI. Results Being single, widowed or separated,
      presenting little or no educational level (66.4 %), suffering from hypertension
      (56.7 %), diabetes (16.8 %) and bone problems (22.0 %), cigarette smoking (64.6
      %), nutritional risk, suffering from depression (20.1 %), or anxiety and
      cognitive impairment (49.6 %), impact negatively on functional capacity of older
      adults in Antioquia. However, younger ages, active social lives, and proper use
      of leisure strengthen good functional capacity in the same population group.
      Conclusions The results of this study indicate that there are demographic factors
      of physical and mental health that negatively affect the functional capacity of
      older adults. Therefore, training them on the issue, in order to recognize these
      factors and their influence on the weakening of functional capacity, is required.

PMID- 28453031
TI  - [Pedestrian exposure to air pollution on routes with heavy vehicular traffic].
AB  - Objective This pilot study aimed to characterize pedestrians' exposure to air
      pollution alongside three routes with high traffic in Bogota, Colombia (ninth
      avenue, eleventh avenue and seventh avenue). Method Black carbon (BC) was used as
      an air quality indicator since it is recognized as a tracer compound for
      emissions from mobile sources. The concentrations of BC were recorded
      continuously with a portable Micro Aethalometer Model AE51. The instrument was
      carried by the people doing the 1.5 kilometer-long routes, while they filled in
      an activity form that recorded the events occurring during the walk. Results A
      direct (observed) relationship between BC concentration peaks and documented
      events at each route was found. Although BC concentrations at all three studied
      corridors indicate an inadequate air quality, different concentration
      distributions were found for each route. The authors attribute this result to the
      difference in the volume of heavy traffic (mainly buses and minibuses). Eleventh
      Avenue was the route with the greatest flow of such vehicles and higher
      concentrations of BC. Conclusion The collected evidence reinforces the importance
      of involving air quality as a critical variable when designing non-motorized
      transport oriented infrastructure.

PMID- 28453032
TI  - [Epidemiological study in mental health: health services use and perception of
      social support].
AB  - Objective The general aim of this non-probabilistic epidemiologic study is to
      detect the levels of mental health symptoms and social support for the residents
      of two neighborhoods in the General Belgrano district in Guaymallen, Mendoza
      Province, Argentina. Methods A random sample of 62 adults was selected, in which
      the proportionality of age and sex were conserved in each quota. Each person was
      interviewed in his/her house using the Cuestionario Epidemiologico de
      Sintomatologia Mental [Epidemiological Questionnaire on Mental Health Symptoms]
      (CESIM) and the Cuestionario de Apoyo Social Comunitario Percibido [Questionnaire
      on Perceived Community Social Support]. In addition, participants were asked
      about sociodemographic factors, self-rated mental health symptoms andv visits to
      services specializing in this area. Results The results show that unemployment, a
      low educational level and a marital status of separation or divorce were related
      to high symptoms in the mental health area. In groups with high symptoms, few
      visits to health services were identified. Conclusions No relationship was found
      between the social support indicators and the level of symptoms.

PMID- 28453033
TI  - [Occupation-, transportation- and leisure-related physical activity: gender
      inequalities in Santander, Colombia].
AB  - Objectives To estimate the prevalence of occupation-, transportation- and leisure
      related physical activity, its compliance with recommendations, and to explore
      its association with demographic and socioeconomic variables in men and women of
      the Department of Santander (Colombia). Methods The sample consisted of 2421
      people between 15 and 64 years of age, participants in the Risk Factors for
      Chronic Diseases of Santander cross-sectional study, developed in 2010. The
      Global Physical Activity Questionnaire was used for data collection. Age-adjusted
      prevalence ratios were calculated and multivariate analysis models were built by
      sex using robust Poisson regression. Results The prevalence of occupational and
      leisure physical activity and compliance with recommendations were lower in
      women. Sexual division of labor and a low socioeconomic level negatively
      influenced physical activity in women, limiting the possibility of practice of
      those principally engaged in unpaid work at home. Young or single men and those
      living in higher socioeconomic areas were more likely to practice physical
      activity in leisure time and meet recommendations. Conclusion Physical activity
      surveillance and related public policies should take into account the
      inequalities between the practice of men and women related to their socioeconomic
      conditions and the sexual division of labor.

PMID- 28453034
TI  - [Occupational characteristics and lifestyle of teachers in a city of northeast
      Brazil].
AB  - Objective To analyze the characteristics of work, lifestyle profile and its
      association with professional development cycles teachers of the state system of
      Jequie (BA). Materials and Methods Cross-sectional study with a random sample of
      304 teachers who answered a questionnaire on sociodemographic information,
      occupational and lifestyle. The phases of professional development cycles adopted
      were: entry, consolidation, diversification and stabilization. For analysis, we
      used descriptive statistics and measures of association using the chi-square test
      (0.05) and multinomial logistic regression. Results It was observed that most
      teachers maintained a regular behavior for the general life style, with the
      increase statistically significant levels only to feed positive behavior.
      Conclusions We conclude that there is need to carry out programs to encourage the
      adoption of an active lifestyle among the teachers, especially after the entry
      phase in his career where negative behavior became more pronounced.

PMID- 28453035
TI  - [Estimating disability-adjusted life-years for subtypes of acute ischemic
      stroke].
AB  - Objective To test the hypothesis that DALYs, estimated individually for each
      patient with acute ischemic stroke upon hospital discharge, without reperfusion
      therapy, are not different between the different subtypes of ischemic stroke.
      Patients and Methods In the Hospital Universitario de la Samaritana in Bogota,
      the health records of patients diagnosed with their first acute ischemic stroke
      event from admission and monitoring to discharge were selected. The subtype of
      acute ischemic stroke was classified according to the criteria established by the
      Trial of Org 10172 in Acute Stroke Treatment (TOAST). DALYs were estimated for
      each patient with acute ischemic stroke at hospital discharge. To establish
      differences of DALYs among the five acute ischemic stroke subtypes (TOAST), the
      Kruskal Wallis test was used. Results Of the 39 cases of acute ischemic stroke,
      17 (43.6 %) were classified as artherosclerosis, 10 (25.6 %) as lacunar events, 6
      (15.4 %) as cardioembolic attacks, and another 6 (15.4 %) cases with unclear
      etiology. At hospital discharge, the estimated total DALYs provided by patients
      with acute ischemic stroke was 316.9 years, without statistically significant
      differences between the subtypes of ischemic stroke. At hospital discharge, the
      average of optimal years free of disability lost by a patient surviving an acute
      ischemic stroke was 8.12. Conclusion Non conclusive results are attributed to the
      concurrence of dissimilar acute clinical care processes and to the risk factors
      distributions, comorbidities and patient complications.

PMID- 28453036
TI  - [Multilevel model for global weight gain rate in the kangaroo-mother program in
      Bogota].
AB  - Objectives To formulate a multilevel model for the longitudinal study of global
      weight gain rate in the Kangaroo-Mother Care Program. Methodology A multilevel
      model is used, taking time and some infant and mother variables in the first
      level. Measures associated with the global weight gain rate are considered for
      the second level. Results At 5 % significance, the intercept and the parameter
      associated to the time (days after birth) squared variable have a significant
      effect on the global rate of weight gain. The slope for the time variable is
      significant at the 6 % level. Also, under this model, we find that the gender
      delay in intrauterine growth of the infant, height and perimeter do not have a
      significant effect on the infant's global rate of weight gain. The weight in the
      various controls performed is significant at the 5 % level. There are differences
      between the two infant's gestational classifications (1: 26 to 40 weeks; 2:
      greater than 40 weeks), and between the infant's weight classifications of the
      categories two with one, and three with one (1: 2500 gm or more; 2: between 1500
      and 2499 gm; 3: less than 1500 gm). Conclusion For each additional appointment,
      the average weight gain rate of the infant decreases. However, the infant keeps
      gaining weight, but not at the same rate as in the initial appointments.

PMID- 28453037
TI  - [Innovative culture and diagnosis related groups in a high complexity hospital,
      Colombia].
AB  - Objectives To characterize the perception of Diagnosis-Related Groups (DRGs) as
      an innovation among physicians, nurses and administrative staff in a hospital in
      Colombia. Methods A case study of innovative culture in a hospital. Surveys and
      focus groups were carried out with the medical, nursing and administrative staff.
      Descriptive statistics were calculated for the perceptions of innovative culture.
      Comparative analysis was done between professional groups. The results of the
      focus groups were transcribed and analyzed to deepen the findings of the surveys.
      Results Significant differences were found in perceptions of the innovative
      culture. The nursing staff were more enthusiastic than doctors when evaluating
      the innovative culture and leadership. Physicians felt more autonomy when
      discussing professional issues. Administrative staff assessed the Hospital's
      disposition to acquire new medical technologies as higher than that of
      physicians. The three groups know little about DRG's. Conclusions When
      implementing a health innovation it is advisable to analyze its effect on the
      professionals who participate in the implementation. Physicians perceive DRGs as
      a threat to their professional autonomy, while nurses see it as a pro-innovation
      force. It is important to involve nursing and administrative staff when
      implementing this kind of innovation.

PMID- 28453038
TI  - [Endemic channel of acute respiratory disease and acute diarrheal disease in
      children under 5 years of age in a district of Bogota].
AB  - Objective Developing a useful tool for planning health care for children under 5
      years of age in the Ciudad Bolivar locality of Bogota, developing an endemic
      channel for acute respiratory disease and acute diarrheal disease in children
      under 5 years of age for the period of 2008 to 2012. Methodology Descriptive
      study with a focus on public health surveillance for the preparation of an
      endemic channel for children under 5 years receiving care services in the Vista
      Hermosa Hospital Level I. Results The incidence of acute respiratory disease for
      a period of five years was identified with a monthly average of 1265 + 79 cases,
      showing two annual peak periods. Acute diarrheal disease, a monthly average of
      243 cases was obtained with a period of higher incidence. Conclusion The correct
      preparation of the endemic channels in primary health care can provide alerts in
      a timely manner from the first level of care and guide decision-making in health
      and help achieve better network management services.

PMID- 28453039
TI  - [Evaluation of drinking-water treatment by Lifestraw(r) and Ceramic-pot filters].
AB  - Objective To evaluate under laboratory conditions, the removal efficiency of
      turbidity and E. coli of two household water filters: LifeStraw(r) family (MF)
      and ceramic pot filter (CPF). Methods The two systems were operated over 6 months
      using two identical control units per system, treating 7.5 L/d of a synthetic
      substrate used as raw water. The turbidity of the substrate was adjusted with
      Kaolinite and the E. coli concentration, with a replica of the ATCC 95922 strain.
      The differences of effluent quality of the systems, in terms of turbidity and E.
      coli, were evaluated with Analysis of Variance (ANOVA). Operative and maintenance
      aspects, that could limit or enhance the use of the systems, were also considered
      in the evaluation. Results The water synthetic substrate quality had an average
      of 32.2 +/- 2.8 NTU for turbidity and 3,9x105 UFC/100 mL for E. coli. Both
      systems reduce the turbidity to values below 2 NTU with an inactivation of 100 %
      of E. coli. Statistical differences were found between the systems in terms of
      turbidity removal, MF being more efficient than the CPF (99,2 +/- 0.4 % and 97.6
      % +/- 1.14, respectively). Conclusions Both systems are suitable for household
      water supply treatment, acheiving the water quality standards established by
      Colombian regulations. The MF was more efficient for suspended solids removal and
      filtration rate, but when economic, operative, and maintenance aspects along with
      social acceptability and lifespan are considered, the CPF seems more suitable,
      especially in rural areas.

PMID- 28453040
TI  - [Experimental model of tooth decay as an educational tool for school-age
      children].
AB  - Objective This work consisted of the construction of an educational in vitro
      model of dental caries that started with an adaptation of Miller's classic
      experiment. Methods In a sterilized and sealed glass jar, a sample paste of human
      saliva was collected and a substrate of manufactured sugar (sucrose) was added.
      In addition, a human tooth with healthy dental crown extracted in dental
      treatment but otherwise healthy was added. Research phase I had the negative
      control sample test (tooth + saliva without added) and the others were opened
      after 1, 2, 3 and 4 months of incubation. This phase was essential for the next
      experimental time development. In phase II, two saliva donors with poor levels of
      oral health habits were recruited. The incubation time (defined by phase I) was 2
      and 3 months for each donor. Results This research data gives the possibility of
      building educational materials about the etiology of tooth decay and its clinical
      evolution. It also makes possible the production of an explanatory sheet about
      how to reproduce this experimental model to be used by school children in
      secondary education. Conclusions Doing this kind of work together at school can
      help reduce inequities in oral health, especially since there is an approximation
      toward the discourses, facilitating the process of information dissemination.

PMID- 28453041
TI  - [Cost effectiveness of calcium supplement in reducing preeclampsia-related
      maternal mortality in Colombia].
AB  - Objectives To estimate the cost-effectiveness of administering calcium (1200 mg
      per day) starting in week 14 of pregnancy to all pregnant women compared to not
      supplying it to reduce the incidence of preeclampsia. Methods A decision tree was
      built in TreeAge(r) with outcome measured in life years gained (LYG) associated
      with the reduction in maternal deaths. Costs were included from the perspective
      of the health system in Colombia and expressed in Colombian pesos in 2014 (COP).
      The discount rate was 0 %. We performed sensitivity univariate and probabilistic
      analyses for costs and effectiveness. Results Compared to no intervention,
      calcium supplement is a dominant alternative. If the incidence of preeclampsia is
      lower than 51.7 per 1 000 pregnant women or the cost per tablet of calcium of 600
      mg is greater than COP $507.85, calcium supplement is no longer a cost-effective
      alternative in Colombia for a threshold of COP $ 45 026 379 (3 times the
      Colombian per capita GDP of 2013 per LYG). Conclusions Supplying calcium to all
      pregnant women from week 14 of gestation is a dominant alternative compared to no
      intervention, which saves 200 LYG, while it decreases costs to the order of COP$5
      933 million per 100.000 pregnant women.

PMID- 28453042
TI  - [Forms of management of the national school meals program].
AB  - The National School Meals Programme (PNAE in Portuguese initials) is a
      supplementary program to education that aims to provide school meals for pupils
      across the school system enrolled in public and philanthropic schools of primary
      education, secondary education, youth education, adult education and
      comprehensive education. The principles of the program are the universality and
      the expansion of student services in order to meet the Organic Law on Food and
      Nutritional Security (LOSAN), as well as the Food Security and Nutrition System.
      The objective of this study is to discuss forms of PNAE management to ensure that
      the students' right to school meals. This study is a reflection on how the
      resources of school meals are being managed, be it with a centralized,
      decentralized, semi-centralized or outsourced model. We conclude that the
      knowledge of the different forms of managing federal resources for food for
      school communities allows for making an informed choice regarding implementation
      and enforcement of PNAE.

PMID- 28453043
TI  - The community study has begun.

PMID- 28453044
TI  - [Psychoactive substance use and violent behavior 11-18 year-old students. Itagui,
      Colombia].
AB  - Objective To determine the association between consumption of psychoactive
      substances (PAS) and violent behavior in middle and high school students (grades
      6 to 11) in the municipality of Itagui, Colombia. Method Cross-sectional study
      with a random sample of 646 middle and high school students. Participants
      volunteered to fill out the survey independently and consent was provided.
      Participants' identity was kept anonymous. The survey contained questions
      regarding socio-demographic characteristics, PAS consumption and violent
      behavior. For these variables a descriptive analysis was conducted. In addition,
      prevalence ratios and 95 % confidence intervals were calculated. Lastly, a
      multivariate analysis was performed to determine association and risk factors.
      Results 646 students satisfactorily answered the survey. The median age was 15
      years [Rq 3]. From this sample, 45.6 % (295) were male and 54.3 % (351) were
      female; 59.3 % (383) had a low socio-economic status, 38.9 % (251) have a medium
      socio-economic status, and 0.8 % (5) have a high socio-economic status. Regarding
      PAS consumption, 53.4% (345) of the participants reported to have consumed at
      least one PAS; 46.9 % (162/345) reported to have consumed alcohol within the last
      year; 15.3 % (53/345) reported to have consumed marihuana. All consumed
      substances were found to be associated with and were identified as a risk factor
      for violent behavior. Conclusions SPA consumption is associated with youth
      violent behavior and represents a risk factor to perform such behavior.
      Substances such as heroin, cocaine, and ecstasy, represent greater risk when
      compared to other analyzed PAS. When the other variables were adjusted,
      cigarettes and inhalants consumption, among others, were no longer a risk factor.

PMID- 28453045
TI  - [Physical fitness reference tables for females in the 10 to 14 age range in
      Chillan (Chile)].
AB  - Objective To develop physical fitness reference tables oriented towards the
      health of female students in the 10 to 14 year age range, in Chillan, Chile.
      Method The present is a cross-sectional study. The sample is composed of 250
      female students in the 10 to 14 year age range. To evaluate health-related
      physical fitness, the following tests were used: Body mass index (BMI),
      Deurengerg Formula (Body fat %), Wells and Dillon's Bench (Flexibility), Sargent
      Jump Test (lower limbs strength, 1 Mile Test (endurance) and the 30 Seconds Sit
      Up Test (focalized muscular endurance). Descriptive statistics were used to
      develop the reference tables. From the results, 5 categories were made: very bad,
      bad, regular, good, and very good. Age was used as a parameter. Results This
      study demonstrates the low level of fitness capacity of the group evaluated when
      compared to national and international references. It shows low levels of
      cardiorespiratory endurance, strength of lower limbs, flexibility, and focalized
      muscular endurance. The present study also shows that being overweight is
      associated with low cardiorespiratory capacity, and that there was a high
      prevalence of this in the sample compared to the national level of overweight and
      obesity in females in the 10-14 age range. Conclusion The tests applied in the
      present study are a reliable and simple tool for assessing the level of health
      related fitness capacity. They can be applied in any educational institution,
      since a large or complex infrastructure for its application is not required.

PMID- 28453046
TI  - Motivation and self-esteem in university students' adherence to physical
      activity.
AB  - Objective This study aimed to determine the association between motivation, self
      esteem and body composition in university students' adherence to physical
      activity. Methods A total of 110 undergraduates from two public universities
      (Federal and State) in Teresina, Piaui state volunteered for the study. Of these,
      75 (68.2 %) were women aged between 18 and 35 years, and 82 (74.5%) the students
      engaged in physical activity. They responded to the Goncalves Motivation Scale
      (2010), which contains five factors: Fun, Competency, Appearance, Health and
      Sociability. Participants also completed the Lages Self-esteem Scale, with
      sixteen items and five dimensions: Introspection, Physical Image, Life
      Satisfaction, Acceptance and Confidence. The Jackson and Pollock (1978 and 1980)
      3-site skinfold protocol was used to measure fat percentage and body composition
      by anthropometry (Filizola scale equipped with stadiometer). Results A
      significant association between the variables self-esteem and Motivation was
      demonstrated, with the Physical iImage dimension exhibiting the highest
      association with the motivational factors Fun, Competency and Sociability.
      Conclusion The findings indicate that adherence to physical activity is
      associated to motivational factors derived from challenging, integrative and fun
      related circumstances.

PMID- 28453047
TI  - Impact of vigorous exercise on serum levels of L-carnitine in prisoners in
      Colombia.
AB  - Objective To assess the effect of a program of vigorous physical exercises on the
      serum concentration of free and total L-carnitine, in male inmates at a prison in
      Boyaca, Colombia. Methods Pre-post intervention population-based study. 44 male
      prisoners with overweight and/or obesity, from a jail in Boyaca, Colombia were
      randomly assigned into two groups: an intervention group and a control group. The
      intervention consisted in participating in a vigorous exercise program over
      twelve weeks. Anthropometric measures and levels of free and total L-carnitine
      were every four weeks. Results There were significant increases in serum levels
      of free and total L-carnitine in the intervention group compared to the control
      group. Concurrently, in this group there was a reduction in body mass index
      (BMI), while in the control group there were no changes. Conclusion In overweight
      and/or obese patients, the routine practice of vigorous exercise plus caloric
      restriction offers significant benefits in reducing body fat volumes through the
      mechanisms of energetic consumption of long chain fatty acids.

PMID- 28453048
TI  - [Use of complementary and alternative therapies in children with cancer].
AB  - : Objective To determine the frequency, characteristics and related factors for
      the use of complementary and alternative therapies in pediatric patients with
      cancer in a Colombian pediatric oncology department. METHODS: Cross-sectional
      study consisting of a survey of 398 caregivers of pediatrics patients with cancer
      evaluated in the Instituto Nacional de Cancerologia in Bogota, Colombia. The
      survey collected sociodemographic and clinical information and evaluated the type
      of complementary and alternative therapies, mechanisms of action, and patterns of
      use of these treatments. Logistic regression was conducted to identify predictors
      of complementary and alternative therapies use. Results In this study
      complementary therapies were used not as a substitute but in addition to
      conventional treatments to cure or to control the disease or to treat symptoms. A
      total of 326 patients (81.9 %, CI95 %: 77.8 % to 85.6 %) had received some type
      of complementary therapy and 81 different types of therapies were used. The most
      common type of complementary therapy corresponded to the group of biologically
      based therapies (mainly berry juices). Female family caregivers with higher
      educational status were more likely to use complementary therapies. Time from
      diagnosis and having received surgical treatment were also associated with the
      use of therapies. Reinforcement of the immune system appears to be the most
      likely mechanism of action. Conclusion A high prevalence of use of complementary
      therapies was found in this sample. Pediatricians need to ask their patients
      about complementary and alternative therapy practices considering the potential
      for interactions with pharmacological treatments or adverse effects.

PMID- 28453049
TI  - [Preliminary analysis of a questionnaire for assessing the social perception of
      air pollution].
AB  - Objective To analyze the psychometric properties and the structural organization
      of a questionnaire designed to assess the social perception of air pollution and
      its health risks in the Valle de Aburra (Colombia), a geographical area where
      environmental problems associated with air pollution have been identified.
      Methods A descriptive study was carried out, in which a questionnaire was
      designed and validated to determine three dimensions of social perception of air
      pollution: the socio-territorial dimension, the socio-cognitive dimension and the
      behavioral dimension. Some socio-demographical variables were also included.
      After the pilot study, the dimensions of the analysis were organized into 12
      categories, made up of 111 items with Likert scales of four or five response
      options. The instrument was applied to a non-random sample of 318 participants,
      who were residents of Medellin city and Girardota town. Results After exploratory
      factor analysis (varimax rotation), the questionnaire was reduced to 68 items
      assessing seven dimensions of social perception of air pollution and its health
      risks. The total variance explained is 75 %, and the overall Cronbach's alpha
      reliability was 0.9. Discussion The dimensions found allow us to develop an
      approach to the structural organization of the social perception of air pollution
      in the context of study. Although some socio-cognitive and behavioral dimensions
      were confirmed, the socio-territorial dimension and the personal involvement
      variable were not configured as structural components and, conceptually, they
      need to be reworked. Confirmatory structural analysis of the dimensions of the
      questionnaire is required.

PMID- 28453050
TI  - [Identification of bacteria and fungi in the air of Neiva, Colombia].
AB  - Objective To isolate and identify microorganisms (bacteria and fungi) present in
      the air in the city of Neiva between the dry and rainy seasons of 2012. Materials
      and Methods Two methods were used for sample collection: sedimentation plates and
      the bio-impactor Millipore M Air T in which the following culture media were
      dispensed: agar tripticase soy (ATS) for bacteria growth, and agar gentamicin
      glucose-yeast extract for fungi growth. The dyes employed included Gram stain and
      lactophenol blue stain. When necessary 10 % KOH was also used. Results According
      to the frequencies of occurrence, Aspergillus spp. and Gram-positive bacilli were
      the predominant microorganisms in the different sampling areas. The genus
      Aureobasidium sp. and Gram-negative bacilli showed occasional, and rare
      occurrence frequency since they are not considered to be air-born microorganisms.
      Conclusions The microbial load was higher in the dry season than in the rainy
      season, appearing more fungal bacterial growth in both seasons of the year. With
      the use of the Bio-impactor, increased growth of both bacteria and fungi could be
      observed as compared to the sedimentation plate method.

PMID- 28453051
TI  - [Aedes aegypti larval infestation index and identification of awareness,
      attitudes and practices related to Dengue in tire shops in Atlantico, Colombia].
AB  - Objective To identify the awareness, attitudes and practices related to dengue in
      owners and workers of tire ships, as well as the levels of mosquito infestation
      in tire shops in Atlantico department - Colombia. Methods We conducted a
      descriptive study. The variables were described as percentages and measures of
      central tendency and dispersion. Index of larval infestation and containers were
      calculated in each of the municipalities studied. We visited and inspected 111
      tire shops. 26.1 % (29/111) of these were found positive for Ae. aegypti larvae.
      The municipalities of Piojo, Santo Tomas, Santa Lucia, Sabanagrande and Luruaco
      were characterized by a higher larval infestation index. Results Regarding
      dengue, 90.9 % of respondents considered it a problem for them and their
      families. 94.6 % know that is transmitted by mosquitoes. 91.1 % know the vector
      larvae under the name "sarapico", 3.6 % as "gusarapo". 98.2 % felt that there is
      a relationship between the larva and Ae. aegypti mosquito. 100 % of participantes
      recognized tires to be a breeding for mosquitoes. 85.7% believed fever to be the
      most common symptom. 83 % reported accessing the health post to cure the disease.
      90.8 % throw out unusable tires as if they were garbage. Conclusion In the
      population studied, there is good awareness of dengue and its vector.
      Nevertheless, there are problems related to attitudes and prevention practices.

PMID- 28453052
TI  - [Ross-Macdonald: A model for the dengue dynamic in Cali, Colombia].
AB  - Dengue is an infection transmitted by mosquitoes and is present in all tropical
      and subtropical regions of the planet. In recent years, the transmission of the
      disease has increased, predominantly in urban and semi-urban areas, and has
      become an important public health problem. The National Health Institute
      (Instituto Nacional de Salud-INS) determined Cali to be the municipality with the
      most cases of dengue in Colombia. According to the INS, up to epidemiological
      week 18 (April 28 to May 4, 2013) 5 134 cases of dengue -and 171 cases of severe
      dengue- have been reported. This study presents a description of the Ross
      Macdonald model, and qualitative analysis of this model, and an analysis of the
      sensitivity of the model to changes in its parameters. Based on the adjustment of
      the model obtained for cases that occurred in 2010, simulations of possible
      scenarios of epidemic outbreaks in the city of Cali are created and analyzed.

PMID- 28453053
TI  - [Nutritional status and food consumption among students admitted to nutrition and
      dietetics programs in the National University Of Colombia].
AB  - Objective To determine the nutritional status and some food intake
      characteristics of first semester nutritional science students. Methods
      Observational, descriptive and transversal study. Sample of 70 students. A survey
      was conducted to determine the food intake characteristics. Anthropometric
      measures were also taken. Excel, Access 2010 and Epi 2002 were used. Measures of
      central tendency, stratified by gender and age, were determined. Results
      According to the BMI measures, approximately three in four students were
      classified as normal. Malnutrition was more prevalent in men than in women.
      Around 70 % of the students consumed milk and dairy products, and nearly 61 %
      consumed meat daily. Roughly half of the students consumed eggs between two and
      three times a week; only 27 % of the students did so every day. 50 % of the
      students said they consumed fruit juice daily, and only 37 % of the survey
      respondents consumed whole fruits with the same frequency. Vegetables were
      reported as less consumed. About 10 % of the students consumed low nutrient
      density food (soft drinks, candies and excess fat in the diet) daily. 5 % of the
      students consumed fast food. Conclusion The students had inappropriate diet and
      eating habits. This is probably related to the prevalence of malnutrition found.

PMID- 28453054
TI  - [Obstetrician-gynecologist's attitudes toward legal and voluntary interruption of
      pregnancy].
AB  - Objective In 2006, Colombia decriminalized legal and voluntary interruption of
      pregnancy (LVIP) in situations in which: the mother's life or health is in
      danger, fetal life-threatening malformations exist, or when the pregnancy is the
      result of rape, non-consensual artificial insemination, or incest. Difficulties
      reported in the introduction of this practice are related to the attitudes of
      doctors. Obstetricians usually are the doctors who attend these cases; an
      assessment of their attitudes regarding this situation was performed. Method
      Qualitative and quantitative. Self-administered anonymous questionnaires were
      applied to obstetricians who work in Bucaramanga on January 30th, 2012.
      Subsequently, semi-structured interviews were performed to a sub-sample of that
      population. Results Important deficits in the knowledge of legislation regarding
      LVIP and conscientious objection were found. Life-threatening for mother, and
      fetal life-threatening malformations were the most accepted items and the most
      likely to be practiced. The item "pregnancy secondary to rape" although accepted,
      was the most objected to for reasons of conscience. Conclusion The inclusion of
      gestational age as a regulatory criterion for LVIP was suggested by the
      interviewees. The joint effect of the findings mentioned above, and both
      administrative and logistic difficulties in the Colombian health system
      constitute barriers for patients in cases of LVIP.

PMID- 28453055
TI  - [Simulation and data mining model for identifying and prediction budget changes
      in the care of patients with hypertension].
AB  - Objective To present a simulation model that establishes the economic impact to
      the health care system produced by the diagnostic evolution of patients suffering
      from arterial hypertension. Methodology The information used corresponds to that
      available in Individual Health Records (RIPs, in Spanish). A statistical
      characterization was carried out and a model for matrix storage in MATLAB was
      proposed. Data mining was used to create predictors. Finally, a simulation
      environment was built to determine the economic cost of diagnostic evolution.
      Results 5.7 % of the population progresses from the diagnosis, and the cost
      overrun associated with it is 43.2 %. Conclusions Results shows the applicability
      and possibility of focussing research on establishing diagnosis relationships
      using all the information reported in the RIPS in order to create econometric
      indicators that can determine which diagnostic evolutions are most relevant to
      budget allocation.

PMID- 28453056
TI  - [Comparison of varnishes and fluoridated toothpaste for the prevention of dental
      caries in school children].
AB  - Objective To compare preventive effect on dental caries of two frequencies of
      fluoridated varnish (FV) applications and a group given brushing instructions and
      using fluoridated toothpaste. Materials and Methods Follow-up study of 203
      children attending an elementary school in the municipality of Tlahuac, Mexico
      City. The children were followed for 22 months. The students were randomly
      assigned to one of the following groups: 1) brushing instructions with
      fluoridated toothpaste, 2) FV every six months, 3) three FV applications per week
      per year. The FV contained fluorosilane (1000 ppm F) and NaF dentifrice (1450 ppm
      F). The DMFT-caries index and the presence of white spots were recorded (ICDAS,
      International Caries Detection and Assessment System). Results At baseline, the
      mean age of the children was 9.3 (SD 0.76) years, white lesions 0.63 (SD 1.48)
      and DMFT =0.70 (SD 1.11). Averages of the initial and final DMFT scores in the
      three groups were 0.67 and 1.17 for the toothpaste group, 0.77 and 1.46 for FV
      twice a year group, and 0.67 y 1.03 for the three-applications-FV group.
      According to the results of the GEE (Generalized-Estimating Equations) model,
      there were no significant differences in the rate of white lesions or the
      increase of the DMFT index. The results for the DMFT were: for bi-annual
      applications of FV, RR=1.24 (p=0.178) and for the three consecutive applications
      of FV, RR=0.83, (p=0.298) in comparison with the brushing-instructions group
      using fluoridated toothpaste, among the three treatment groups, controlling for
      age, sex, and initial-caries index in primary teeth and brushing frequency.
      Conclusions Schoolchildren showed a low incidence of caries using any of the
      three preventive regimens applied.

PMID- 28453057
TI  - [Correlation of size and age in Colombian indigenous children based on WHO and
      NCHS references].
AB  - Objective To evaluate the correlation of size, according to age, of the
      anthropometric growth references of Colombian indigenous children studied in
      Encuesta Nacional de la Situacion Nutricional de Colombia 2010 -ENSIN 2010
      (National Survey of Nutrition in Colombia - 2010). Method A secondary analysis of
      2598 data of indigenous Colombian children under five years of age, evaluated by
      ENSIN in 2010, was performed. The considered variables were size according to
      age, gender, height, place of residence, department and socioeconomic position.
      The classification of the deficit in size, based on the references of the
      National Center for Health Statistics (NCHS) and the World Health Organization
      (WHO), was made by using the Z <-2 score and the Anthro software. The Kappa
      coefficient was estimated to assess the correlation between anthropometric
      categories and was classified taking into account the proposal of Altman DG.
      Results One in four children had a deficit in size in the light of both
      anthropometric references. The prevalence of the deficit was higher when using
      the WHO standard, increased with age and was higher in children who resided in
      low altitude (m). The correlation between the two references was good (kappa
      >=0,688, p=0,000) for children of both genders and all ages; the exception
      corresponded to children of age two, since it was moderate (kappa=0,601,
      p=0,000). The greatest disagreement in the classification was observed in the
      category "tall". Conclusion According to the statistical correlation found
      between the two anthropometric references (WHO vs. NCHS), any reference could be
      used for assessment of size according to for age.

PMID- 28453058
TI  - [Socioeconomic factors conditioning obesity in adults. Evidence based on quantile
      regression and panel data].
AB  - Objective To measure the effect of socioeconomic variables on the prevalence of
      obesity. Factors such as income level, urbanization, incorporation of women into
      the labor market and access to unhealthy foods are considered in this paper.
      Method Econometric estimates of the proportion of obese men and women by country
      were calculated using models based on panel data and quantile regressions, with
      data from 192 countries for the period 2002-2005.Levels of per capita income,
      urbanization, income/big mac ratio price and labor indicators for female
      population were considered as explanatory variables. Results Factors that have
      influence over obesity in adults differ between men and women; accessibility to
      fast food is related to male obesity, while the employment mode causes higher
      rates in women. The underlying socioeconomic factors for obesity are also
      different depending on the magnitude of this problem in each country; in
      countries with low prevalence, a greater level of income favor the transition to
      obesogenic habits, while a higher income level mitigates the problem in those
      countries with high rates of obesity. Discussion Identifying the socio-economic
      causes of the significant increase in the prevalence of obesity is essential for
      the implementation of effective strategies for prevention, since this condition
      not only affects the quality of life of those who suffer from it but also puts
      pressure on health systems due to the treatment costs of associated diseases.

PMID- 28453059
TI  - [Public health in the health-disease continuum: an analysis from a professional
      perspective].
AB  - Objective To explore the components that health professionals use to build and
      define the concept of Public Health as a specific area of knowledge and
      intervention within public health policies. Method A qualitative analysis of
      content was performed based on 20 semi-structured interviews with health
      professionals participating in the demonstration project conducted by the Public
      Health Agency of Garrotxa in Catalonia, Spain (2009-2012). Results Health
      professionals use the health-disease continuum to provide guidance to all State
      policies on health: public health is usually related to health and care regarding
      disease. Also, professionals contrast public health against health care to define
      and delineate each intervention area based on the approach, the objectives, the
      demand, the timing, the invisibility and the consistency. Discussion The
      continuum health-disease is a relevant element to guide public health policies.
      It is necessary to develop the concept of wellbeing to act under a positive view
      of health. Moreover, recognizing the multiplicity of elements that affect public
      health makes it permeable to the initiatives of other institutions, while they
      turn to Public Health in other areas of intervention.

PMID- 28453060
TI  - [Physician-patient relationship: Impact on promotion and prevention campaigns for
      patients with HIV in Medellin].
AB  - : Objective To understand the impact that healthcare professionals have on the
      perception of health promotion and disease prevention campaigns of individuals
      with HIV in Medellin, Colombia in 2012. MATERIALS AND METHODS: The research was
      conducted using a qualitative approach, based on the Strauss and Corbin's
      Grounded Theory; thirteen people were interviewed during two sequential steps.
      The interviews were transcribed and analyzed in accordance with the theory
      mentioned above, by performing an open and axial coding on the data found.
      Results A total of 1 324 codes were generated in the open coding process
      (creating six descriptive categories) and axial coding process (identifying four
      analytical categories; one of them is developed as a result in this paper). The
      most relevant findings included the importance given by the participants to the
      role of health professionals when supporting HIV-positive patients in the
      acquisition of healthy lifestyles to properly manage their condition. Also, the
      role that those people who already contracted the virus have for the promotion of
      sexual behaviors to minimize the risk of infection is stated. Conclusion The
      doctor-patient relationship poses great challenges in terms of health services
      management for the different actors of the system. Likewise, these challenges
      must be taken into account when creating future public policies.

PMID- 28453061
TI  - [Roles and challenges of female heads of household with HIV/AIDS].
AB  - Objective To characterize the roles and challenges that female heads of
      households with HIV in Valle del Cauca, Colombia assume. Method A qualitative
      exploratory method, based on Grounded Theory was conducted. Data were collected
      through in depth interviews to 13 women with HIV, heads of household with ages
      between 19 and 46,who live in the cities of Cali and Buenaventura. Results The
      main roles assumed by women are taking care of their children and their homes,
      expressing affection, providing support during different life events and
      administrative procedures related to health care services access. The challenges
      expressed by these women include aspects related to parenting, being a self-care
      role model, accompanying and leading the diagnosis and adherence to the treatment
      children with HIV, revealing the diagnosis, providing the best living conditions,
      and providing access to goods and services. Conclusions The results of the study
      highlight the challenges that women living with a chronic illness, that is still
      loaded with stigma and discrimination, have to face. The social, economic,
      cultural and health aspects related to the inequities and inequalities in health,
      to gender and access to health services, to decent work and to education are made
      clear in this work.

PMID- 28453062
TI  - Disease burden and medical cost-analysis of Acute Respiratory Infections in a low
      income district of Bogota.
AB  - Objective To estimate the burden of disease and related direct medical cost of
      Acute Respiratory Infections (ARI) for the health-care system in a low-income
      district of Bogota, generated by children under age five and senior population
      over age sixty. Methods A cross-sectional, retrospective, patient level study was
      conducted in San Cristobal district from 2008 to 2012 among the subsidized
      population. All inpatients and outpatients with ARI from three hospitals were
      reported. The total and average direct medical costs were estimated and are
      reported in International Dollars (Int$). Results It is estimated that, for
      children, ambulatory incidence rate for ARI varied between 54.4 % and 66.3 % and
      hospitalization rate between 9.2 % and 12.3 %. The mortality rate in the district
      oscillated between 18.1 and 27.7 deaths per 100 000. The main medical costs were
      attributed to hospitalizations, and the total medical hospitalization cost per
      year estimated ranged between Int$ 1 334 352 and Int$ 2 139 597. In the case of
      senior population, the ambulatory incidence rate fluctuated between 7.6 % and
      10.0 %, and the hospitalization rates between 0.6 % and 2.1 %; the mortality rate
      ranged between 8.9 and 47.8 deaths per 100 000. Hospitalization cost per year was
      estimated to be between Int$ 88 957 and Int$ 373 382. Conclusion Direct medical
      costs due to ARI have an important disease and direct medical cost burden in this
      low-income district.

PMID- 28453063
TI  - Epidemiological surveillance of herpes viral encephalitis in Cordoba, Colombia.
AB  - Objective To establish an epidemiological surveillance of viral herpes
      encephalitis in major hospitals of Monteria, Cordoba. Methods From September 2009
      to December 2011, a descriptive study of cases of viral encephalitis was made in
      three hospitals in the city of Monteria. Cerebrospinal fluid (CSF) samples from
      118 patients were included in the study. Clinical aspects, as well as
      cytochemical and microbiological analysis (Gram stain and culture) of CSF, were
      used for selecting the patients. Virus detection was performed by using multiplex
      nested PCR for Herpes simplex virus 1 and 2, Epstein Barr virus, Cytomegalovirus
      and Varicella zoster virus. Results Viral DNA of herpesvirus was detected in the
      CSFs of 30 (25.4 %) participants, as follows: 22 (18.6 %) Herpes simplex 1 and 2
      viruses, 4 (3.3 %) Cytomegalovirus and 1 (0.8 %) Varicella zoster virus. Co
      infections were observed in 3 patients (2.5 %), 1 case by HSV-VZV and 2 cases by
      CMV/HSV. The clinical manifestations of the patients included: headache (18.6 %),
      fever (14.4 %), asthenia (10.1 %), seizures (9.3 %), vomiting (8.4 %), and stiff
      neck (5.9 %). Thirty percent of the patients also had HIV-AIDS. A case fatality
      rate of 20 % was observed for the patients. Conclusions This paper shows that
      herpesvirus is a cause of infection of the CNS in patients from Cordoba. This
      study contributes to the epidemiology of encephalitis, as well as to patient
      management.

PMID- 28453064
TI  - [Diagnosis of healthcare issues in clinics and hospital of Barranquilla].
AB  - Objective To identify and assess the main healthcare issues found in clinics and
      hospitals in Barranquilla. Methods Descriptive study applied on two populations:
      clinics [23] and hospitals [5]. A confidence level of 95 % and the alpha level of
      5 % and p=0.5 were used in the study. The resulting sample size for clinics and
      hospitals was 18 and 4, respectively. Clinics and hospitals were randomly and a
      21-question survey was designed to find out the status of the different
      healthcare processes in the Health Care Sector. The results were processed by
      using Microsoft Excel 2010 software. Results On one hand, 50 % of the hospitals
      expressed having problems in outpatient, hospitalization and statistical
      departments. On the other hand, 61.1 % of the clinics have difficulties in
      Emergency rooms, 50 % in Surgical Services, 50% in Hospitalization and 38.9 % in
      Outpatient Department. Conclusions The diagnosis regarding healthcare issues in
      clinics and hospitals of Barranquilla determines that although the
      Hospitalization process is a common point for potential improvement in both
      hospitals and clinics of the city, the greatest priority should be given to
      Surgical Services, Emergency Department and Statistical Department, due to their
      average intervention priority.

PMID- 28453065
TI  - [Identification of capacities in environmental health from environmental
      authorities in Colombia].
AB  - Objectives To diagnose the capabilities that environmental authorities and the
      Ministry of Environment and Sustainable Development have to assume their role in
      environmental health, based on the capacity model of the United Nations Program
      for Development UNDP. Method Document review, interviews on key issues and a
      commented survey were conducted. 84 entities were selected for a tailored survey;
      complete information was obtained from 76 institutions. Results The valuation of
      environment favorability was within the acceptable and unfavorable categories;
      knowledge management capabilities were found to be precarious and assessment of
      functional capabilities ranged between appropriate and acceptable. The assessment
      of specific capabilities had a rating of poor or barely acceptable. Conclusions
      Two major problems were found: a. The environmental authorities do not conceive
      or implement these capabilities based on the UNDP model but on the conventional
      model of the Ministry of Environment, Housing and Territorial Development; b.
      Environmental authorities show an incipient level of incorporation of
      environmental health policies in their field of action.

PMID- 28453066
TI  - [Determining social factors related to pesticide poisoning among rice farmers in
      Colombia].
AB  - Objective Large quantities of pesticides are used in rice crops. The aim of this
      study is to characterize how farmers are exposed to pesticides and subsequent
      poisoning. Materials and Methods A multilevel (individual and community) multi
      method study, which included ethnographic and survey methods, as well as
      measurement of pesticides in water and human samples, was performed. Results The
      production process is described and the main risk factors are presented.
      Pesticides are considered the greatest danger at work and at their homes. Workers
      have poor working conditions and are not protected by the system of occupational
      risks. Azinphos-methyl, endosulfan, beta-BHC, bromophos-methyl, bromophos-ethyl
      and 2,4- DDT were found in water samples. The survey included 381 workers with
      mild (12.86 %), moderate (67.98 %) and severe (5.51 %) poisonings respectively.
      Severe cases presented lower levels of education, lower levels of health care
      access to the contributory regimen of the Colombian social security system and
      higher incidence of cardiovascular disease, diabetes, herpes or other viral
      infections. Conclusion There are precarious working conditions that favor
      exposure to pesticides correlated to the exclusion of farmers from the
      occupational risk system, to poverty and to poor education. It is urgent to
      include these workers to the system of occupational risk system and to improve
      their living conditions, thus reducing unsafe practices when handling pesticides.

PMID- 28453067
TI  - [Systematic review on the physical activity level and nutritional status of
      Brazilian children].
AB  - Objective To systematically review the literature on the prevalence and the
      factors associated with physical activity level and nutritional status of
      Brazilian children. Methods The electronic database MEDLINE (via PubMed), SciELO,
      SCOPUS and Web of Science were selected. The search strategy included the
      descriptors proposed in the Medical Subject Headings (MeSH): "Motor Activity",
      "Activities", "Nutritional Status", "Overweight", "Obesity", "Body Mass Index",
      "Child", "Brazil". Results The search allowed the identification of 141 articles,
      of which 16 studies were considered potentially relevant and were included in the
      review. Conclusions Studies about nutritional status and physical activity levels
      in Brazilian children are still scarce, but the work on this has increased in
      recent years, especially those that use cross designs, as well as questionnaires
      to measure physical activity; BMI for nutritional status is still widely used.
      Furthermore, studies that analyzed the amount of hours designated to sedentary
      behaviors such as watching TV, playing video-games and using the computer, found
      that these activities took more than two hours every day.

PMID- 28453068
TI  - [Obesity risk in preschoolers beneficiaries of food aid programs].
AB  - Objective To review the evidence regarding the potential impact of food programs
      on the risk of obesity in beneficiary children. Methods The search was conducted
      in databases using terms in Spanish and English. Those items that included the
      variable of interest, cross sectional studies, cohort or community trials were
      selected. Results Food assistance programs could contribute to increased obesity
      rates in the target population due to the availability and easier access to food
      with high energy content, either through the delivery of provisions or cash.
      However, the impact of the programs on this outcome has been little studied and
      evaluations have been mostly in adults or school-age children. Conclusion This
      review contributes to knowledge about the possible effect that food programs have
      on the risk of obesity in beneficiary children. This review may also serve as a
      reference for the design, implementation and evaluation of food and nutrition
      programs in countries of low and middle income facing malnutrition.

PMID- 28453069
TI  - [Double burden malnutrition during growth: is becoming a reality in Colombia?]
AB  - Several reports have described in the last decade the coexistence of accelerated
      increase of obesity with micronutrient deficiencies in developed countries, and
      is becoming evident in developing nations. This condition may be especially
      deleterious in children and adolescents with consequences in metabolic risk and
      growth since early in life. This review describes the evidence of double burden
      malnutrition during growth period focused on six nutrients (iron, zinc, calcium,
      vitamin D, vitamin A, sodium, folic acid and vitamin B12) and its biological
      mechanisms associated with non-communicable disease through span life. In
      Colombia, according to the last national health and nutrition surveys (2005 vs.
      2010), there is an increase in the prevalence of obesity in all age groups; that
      is accompanied with alarming figures of zinc and vitamin A deficiency and anemia
      in children under 5 years. This reality of double burden malnutrition should be
      considered urgently on the public health agenda, implementing robust strategies
      adapted to the reality of the country based on scientific evidence to prevent
      mobility and mortality associated with this condition.

PMID- 28453070
TI  - [The influence of sexual development on the basic physical characteristics of
      teenage boys].
AB  - Objective The objective of this study was to evaluate the effects of sexual
      maturation on anthropometric parameters and basic physical characteristics in
      male adolescents aged from ten to fourteen years old. Materials and Methods The
      biological age was studied through the evaluation of the stage of the external
      genitalia development. Other evaluated characteristics were: total body mass
      (MCT), stature, body mass index (BMI), bone age (IO), strength, speed, agility
      and aerobic power. Results The results showed significant differences in all
      variables related to growth (chronological age, height, total body mass, body
      mass index and bone age) between different stages of sexual maturation. In
      relation to physical qualities, among maturational stages, we find significant
      differences in most characteristics, except for agility. Conclusions Based on
      this study, we may conclude that sexual maturation, evaluated by the stages of
      development of the external genitalia, exerts great influence on the
      anthropometric variables, the bone age and the basic physical characteristics of
      adolescent boys.

PMID- 28453071
TI  - [Quality of clinical and neurologic monitoring in a cohort of extremely premature
      infants, 2002-2012].
AB  - Objective To explore the clinical course of a cohort of newborns <1000 gr or <29
      weeks of gestational age at birth after discharge from the Kangaroo Mother Care
      Program (KMC). Method Telephone surveys with parents of a cohort of 569 premature
      babies treated in 3 KMC programs between 2002 and 2012. Results The study
      contacted 65.4 % of the cohort, averaging 4 years old. 34 patients (6 %) passed
      away, 65 % during the first 6 months of life. 63 % were re-hospitalized, 32 %
      presented antecedents of intraventricular hemorrhage, 30 % had chronic lung
      disease, 5.2 % had cerebral palsy or mental retardation, and 2.7 % had
      convulsions. 72 % were monitored by a pediatrician, 65 % needed physical therapy,
      and 39 % needed speech therapy. 7 % repeated years in school and 9% of those over
      4 years old had not begun to write. 4 % of those who could write had
      difficulties. 81 % of those over 6 years old had difficulties dressing
      themselves; 55 % did not practice sports. Discussion Extremely premature or low
      birth weight premature babies have a higher level of respiratory and neurological
      consequences that affect their quality of life and that of their family. It is
      important to strictly monitor their health after 12 months in order to promptly
      detect and manage neuro-psychomotor and sensorial development disorders.

PMID- 28453072
TI  - [Urban outbreak of visceral leishmaniasis in Neiva (Colombia)].
AB  - Objective Characterize the foci of visceral leishmaniasis infection in Neiva with
      a clinical and epidemiological approach. Materials and Methods Six children
      consulted medical services with hepatosplenomegaly. They were found to have
      anemia and leukopenia. The diagnosis was performed by bone marrow (five patients)
      and spleen (1 patient) aspiration. An active search for cases was carried out in
      the community. Anti-Leishmania infantum antibodies were also sought out using
      indirect immunofluorescence (IIF) in symptomatic patients and in dogs (IFI,
      rK39). House calls were made in order to carry out educational activities and to
      collect disease vectors. Patients received miltefosine, amphotericin B or
      Glucantime(r). Results LV was confirmed in seven children. In six of them, the
      bone marrow or spleen aspirate contained amastigotes. The IIF was positive in 4
      patients and negative in 3. One child was detected throught the active community
      search, confirmed by the clinic with IIF (1:32). Six patients were cured with
      liposomal amphotericin B (o deoxycholate) and one patient was cured with
      Glucantime(r). The canine seroprevalence in 1182 dogs was 6.1% (IFI and rK39);
      the positive animals were destroyed. L. longipalpis was found in the houses. This
      is the principal vector of LV in Colombia. Conclusions The study showed that two
      zones of Neiva have children infected with LV. Diagnostic confirmation must
      include aspiration of bone marrow and IIFs. Treatment with miltefosine was not
      helpful, but liposomal amphotericin B is an ideal therapy. To control LV, active
      case searching, community education and vector and reservoir control is
      necessary.

PMID- 28453073
TI  - [Adherence to treatment for HIV/AIDS: beyond the uptake of antiretrovirals].
AB  - Objective To describe adherence to non-pharmacological treatment in HIV/Aids
      diagnosed patients from Cali, Colombia, and its relation to socio-demographic
      factors. Material and Methods Observational cross-sectional study, with a sample
      of 277 HIV/AIDS diagnosed patients from nine health care centers. The Adherence
      to Treatment for HIV/AIDS Questionnaire was used as a measurement tool. Results
      37 % of patients were adherent to non-pharmacological treatment. The analysis of
      the socio-demographic related factors shows that patients with less opportunity
      to adhere to non-pharmacological treatment were those younger than 40 years.
      Conclusions Adherence to non-pharmacological treatment was low and seems to be a
      generalized problem in HIV/Aids population, being lower in people younger than 40
      years. Results show the need to conduct interventions aimed at improving non
      pharmacological adherence, in order to contribute to infection control.
      Interventions should be implemented in all the diagnosed patients, with special
      emphasis on youth.

PMID- 28453074
TI  - [Knowledge of people living with HIV/AIDS virus regarding the disease].
AB  - Objective To determine the knowledge of people living with HIV/AIDS (PLWHIV/AIDS)
      towards the disease. Methods A cross-sectional study was designed for a sample of
      260 persons. A validated questionnaire, developed by the authors was used; it was
      structured into 35 questions regarding generalities and the mode of transmission
      of the disease. Results A high proportion of the participants were males (59.6
      %), the mean age was 35.45+/-10.90 years, the median time of diagnosis of the
      participants was 3 years. 30 % of the participants had an elementary school
      educational level. 3.5 % had a "good" general knowledge. Statistically
      significant difference was observed between "deficient" and "fair" knowledge and
      educational level (p<0.000). 10.5 % of the females did not know that "HIV is
      transmitted through breast feeding", however, a statistically significant
      difference was observed between genders (p<0.009). 67.6 % did not know the most
      frequent opportunistic disease of the oral cavity among PLWHIV/AIDS. No
      statistically significant difference (p>0.05) was observed between educational
      level and the knowledge about questions related to CD4 cells. Statistically
      significant difference was observed between time of diagnosis and breast feeding
      as mode of transmission. Conclusion There is a need to develop educational
      programs geared towards PLWHIV/AIDS in order to improve their knowledge towards
      the disease and their quality of life.

PMID- 28453075
TI  - [Characterization of the training and practice of human talent working in
      environmental health in Colombia].
AB  - Objectives To characterize the peculiarities in the training, exercise, and
      performance of human talent working in environmental health in Colombia. Method
      Documentary and database reviews. Surveys and semi-structured interviews. Results
      Approximately 70 % of professionals in the area of environmental health work in
      health management, food engineering, environmental engineering, sanitary
      engineering, veterinary medicine, and pharmaceutical chemistry. 63 % of
      technologists belong to the field of sanitation technology. Only 20 % of surveyed
      educational institutions apply the competence approach to training to their
      students and the identification of occupational characteristics in the labor
      market is only used at the undergraduate level as a criterion of academic
      analysis and design. Only 20 % of educational institutions identify educational
      trends in Colombian and or international environmental health as a contribution
      to their programs. In prospective practices, the following topics to be
      strengthened were identified: risk factor identfication, measurement, and
      control; design and implementation of mechanisms for controlling environmental
      risks; forms of interdisciplinary work between the natural, social and health
      sciences; preventative and environmental protection measures and the concept of
      environment (natural, social, and cultural). Conclusion The human talent
      currently working in environmental health in the country is concentrated in
      primary care activities (inspection, monitoring and control) and a large spread
      exists in mission processes and competences, both professionally and
      technologically. A lack of coordination between the environmental sector and the
      education sector can be observed. A great diversity exists among the profiles
      offered by the different educational programs related to environmental health.

PMID- 28453076
TI  - [Pharmacological evaluation of osteoporosis and osteopenia treatment in an
      institution under the special health system in Bogota].
AB  - Objetive To evaluate habits related to the prescription of drugs used in the
      treatment of osteoporosis and osteopenia in a health institution in Bogota as
      compared to two international clinical practice guidelines. Methodology An
      observation and cross-sectional study with retrospective data collection. It is a
      study of drug-prescribing habits. Information was taken from 331 patients treated
      with bisphosphonates, calcium salts, strontium ranelate and teriparatide. The
      prescription habits were assessed by way of a comparison with the NOF clinician's
      guide for the prevention and treatment of osteoporosis and the National Institute
      for Health and Clinical Excellence (NICE) guidelines. Results 89 % of the
      population were women with an average age of 67 years. The dose and frequency of
      the administration of drugs was in accordance with established guidelines. 32.2 %
      of patients were treated with bisphosphonates for over 3 years, 94.2% were
      treated with primary prevention, and 89.6 % had been treated without any
      osteoporosis diagnosis by DMO. Compared to the NOF guide, 67.3 % of the patients
      were treated unnecessarily. Conclusions The drug prescription habits used in the
      treatment of the osteoporosis do not follow the guidelines, showing non-adequate
      use, especially of bisphosphonates.

PMID- 28453077
TI  - [Validation of an instrument to assess caregiver burden in cerebral palsy cases].
AB  - Objective To develop and validate a scale for assessing the difficulties of daily
      care of children with severe cerebral palsy (CP) at functional levels IV and V on
      the GMFCS (Gross Motor Function Classification System). Materials and Methods A
      validation study was performed by means of a questionnaire to 108 caregivers of
      children with CP. The first phase of the study aimed to develop the questionnaire
      and conduct a pilot experiment. The second phase covered the application of the
      scale. Finally, the third phase consisted of a psychometric analysis (construct
      and criterion-related validity, internal consistency) and the determination of
      the scale's utility. For the retest, the questionnaire was applied to 62
      patients. Results A scale was developed with 10 items from two domains. The
      internal consistency was very good with a Cronbach's alpha of 0.87. For the
      criterion-related validity, a Pearson's correlation coefficient of 0.71 was
      obtained when the scale was compared to the GMFCS's functional levels. For the
      reliability retest, a Pearson's correlation coefficient higher than 0.87 for each
      of the items was found. Conclusions The "Caregiver Scale" is a valid and reliable
      instrument. Its usefulness for measuring the difficulties in the care of children
      with severe CP is acceptable.

PMID- 28453078
TI  - [Self-rated health in elderly adults and physical health, mental health, and
      geriatric syndrome outcomes in Santiago de Cali].
AB  - Objective To determine the relation between bad self-rated health (SRH) and
      outcomes of physical and mental health and geriatric syndromes over one year.
      Methods A prospective study. A cohort of 231 adults over 60 years of age from
      commune 18 in Santiago de Cali, Colombia were classified into good and poor self
      rated of health status according to results of a primary measurement carried out
      in 2009 and re-measured with the same instrument in 2010. The variables evaluated
      were physical and mental health, functional deterioration, geriatric syndromes,
      and use of health services. Parametric and non-parametric statistical tests were
      used through the module of complex samples of the statistical package SPSS
      version 17. Results After a year of monitoring, the incidence of mortality was
      higher among older adults with poor self-perceived health. Important differences
      were observed in: self-perception of recent weight loss (p=0.009); self
      perception of undeliberate weight loss (p=0.065); self-report of suspension of
      any activity (p=0.001); self-report of having done less things or activities than
      before (p=0.011); self-report of having felt their movements were slower
      (p=0.002); self-report of feeling without energy (0.001); weakened grab power and
      decreased of walking speed (p <0.05). Conclusion The elderly adults with poor
      self-perceived health status presented greater health deterioration, geriatric
      syndromes, and higher frequency of use of health services.

PMID- 28453079
TI  - [Use of dental prostheses and their relationship with oral lesions].
AB  - Objective To show the relationship between dental prostheses and the incidence
      and type of oral lesions developed in the Serido region of Brazil. Methods 77
      patients were registered. All were over 21 years of age, of both sexes, non
      alcoholic and / or chronic smokers, and residents of the municipalities of the
      region corresponding to Serido. They also all had some type of oral lesion and
      had been admitted to dental clinics of the University of Rio Grande do Norte.
      Here, the relationship between these lesions and the dental prostheses that they
      used was observed. Results The majority of dental prostheses related to oral
      lesions had more than 5 years of use and required changing. Candidiasis (45.5 %)
      and inflammatory fibrous hyperplasia (27.2 %) were the lesions most related to
      the dental prostheses. Conclusions Complete prostheses and removable partial
      dentures correlated with oral lesions. However, the complete prostheses had a
      higher percentage ready for change-out and had more than 05 years of use. This
      demonstrates that removable partial dentures, even without the need for exchange,
      showed a high correlation with the oral lesions.

PMID- 28453080
TI  - [The role of occupational therapy in contexts of armed conflict and the post
      conflict].
AB  - Objective To identify professional experiences of Occupational Therapy in
      Colombian and international contexts of armed conflict and post-conflict. Methods
      A qualitative systematic review of the literature between 2005-2014 in five
      analytical categories: professional experiences, problem situations, populations,
      theoretical frameworks, and procedures. Results 78 papers were retrieved.
      Colombian context: the models most used are human occupation and occupational
      performance; the most frequent problem is forced displacement. International
      context: 19 countries documented experiences; the Canadian model and the
      community-based rehabilitation model are most used; the main problem situations
      are forced displacement, refugee status, and attention to members of the armed
      forces. Both contexts highlight procedures such as artistic activities and
      interventions related to social welfare and social-inclusion. Conclusions
      Graduate these are the main source of Colombian experiences, though few are
      published; there are a few studies about victim population (demobilized). The
      rural sector as a typical scenario of armed conflict and a context of
      displacement have been seen as relevant. Frequent conceptual categories and
      practices have been introduced from the critical perspective of Occupational
      Therapy which reinforce the role of the professional in phenomena of social
      exclusion and violence, as a transformational agent that addresses the socio
      political dimension of human occupation. These findings posit challenges for
      professionals and academics to publish, to work with populations (victims or
      not), to approach training and practice in rural contexts, and to recognize the
      role of the professional as an agent that transcends the public health dimension
      of human occupation.

PMID- 28453081
TI  - [The Commission of Health Regulation: chronicle of an end foretold].
AB  - This article aims to establish some difficulties presented in the Commission of
      Health Regulation (CRES, Comision de Regulacion en Salud) during its short period
      of operation and the need for a regulatory body separate from the Ministry of
      Health and Social Protection that has a more pluralistic, participatory and
      inclusive character. We mention that the National Council of Social Security in
      Health (CNSSS -Consejo Nacional de Seguridad Social en Salud) sought to correct
      certain problematic situations, among other things, by creating the CRES.
      However, the national government intended to liquidate the newly formed body as
      already hinted in Law 1438 of 2012. We conclude that despite difficulties in the
      regulatory function, the CRES was eventually liquidated. The creation of a body
      such as the CNSSS that has a wider and more equitable base and that includes all
      social, governmental, and private stakeholders is necessary. This can be deduced
      from the proposed Statutory Law No. 105 of 2012 of the Senate of the Republic,
      which was presented by various social forces.

PMID- 28453082
TI  - [Cultural Identity, social health, and the Social State Under the rule of law.
      The case of "The Quimbaya Treasure". Quindio, Colombia].
AB  - We approach the concept of "cultural identity" as a cohesive element within a
      group in the context of history and territory. We posit the relationship between
      this cultural identity with symbols of affiliation and origin, such as
      archeological heritage; in this case "The Quimbaya Treasure". We present "social
      health" as the capacity of a community, immersed in a culture and a territory, to
      relate healthily and cherish sentiments of support and trust. Rudiments of
      identity such as ancestral legacies allow for the creation of feelings of
      "sociocultural belonging" and self-determination of peoples that take paret in
      the health of a society. The autonomy of peoples and the recognition of their
      diversity appear in the notion of Nation State and Social State Under the Rule of
      Law. In this document, it is argued that, though the construction of this state
      was a political task, the edification of the nation was not. This edification was
      the result of earlier cultural labor. Nevertheless, historical rights are
      reflected in established constitutions. The Quimbaya Treasure was donated to
      Spain as part of Colombia's participation in ceremonies commemorating the 400th
      anniversary of the "Discovery of the Americas". This essay documents the
      legislative acts that prove the inconstitutionality of that donation and, as a
      result, the treasure's possible repatriation. It places emphasis on the
      importance of the repatriation given the value it possesses as an agent of
      cultural identity for Colombians in general and the residents of Quindio in
      particular.

PMID- 28453083
TI  - ?

PMID- 28453084
TI  - [Social network analysis: an effective tool for evaluating community coalitions].
AB  - Objectives The aim of this paper is to report: a. The main applications of Social
      Network Analysis (SNA) in the study of community coalitions and inter
      organizational networks; b. The structural indicators of the whole network
      related to coalition functions, and; c. The methods to identify subgroups within
      networks. Method We will use graph visualization and data from our own research
      to illustrate the procedures under study. Results A set of methodological
      guidelines to evaluate and improve community coalitions through SNA are proposed.
      Conclusions Structural analysis is a powerful instrument to evaluate and optimize
      the functioning of coalitions that provides social and health services, and at
      the same time, it is necessary to understand the specific context of interaction
      and use qualitative tools to contrast the results obtained through SNA.

PMID- 28453085
TI  - Environmental justice and air quality in Santiago de Chile.
AB  - Objective The metropolitan region in Santiago, Chile has an air quality problem.
      However, the larger issue may lie in the inequities created by the distribution
      of the air pollution. Methods To assess the inequities created by the spatial
      differences in air pollution, the author analyzed fine particle pollution levels
      for 2008-2011 at monitoring stations throughout the region. The author also
      compared air quality data with socioeconomic data. Results The areas of the
      Santiago metropolitan region with the worst air quality have lower socioeconomic
      levels. Pollution in these areas reaches levels higher than the current Chilean
      24 hour standard for fine particles. These areas also have longer time periods of
      unhealthy air and 21 % more days with unhealthy levels of air pollution.
      Discussion The differences in exposure to pollution create an inequality and
      environmental injustice among the socioeconomic groups in the metropolitan
      region. Chilean policymakers have the regulatory tools needed to improve
      environmental justice. However, they need to improve the implementation of these
      tools in order to achieve that goal: Chilean policy makers should consider local
      sources of air pollution in the most polluted municipalities; Government decision
      makers should make extra efforts to listen to the community and improve access to
      environmental information; Environmental justice advocates should involve
      stakeholders from the social justice movement and other related areas; Policy
      makers should track progress towards environmental justice by evaluating
      differences in health outcomes related to differential exposure to air pollution
      in different parts of the Santiago metropolitan area.

PMID- 28453086
TI  - [Climatic analysis of heavy metal concentration associated with urban road
      deposited sediment].
AB  - Objective To climatically assess (daily) the concentration of heavy metals (Pb
      and Cu) in sediment deposited on road surfaces of the localities of Kennedy and
      Puente Aranda (Bogota, D.C., Colombia). Additionally, the detected concentrations
      are to be evaluated with respect to the legislation chosen as reference point for
      the protection of human health in urban areas. Methods The concentration was
      determined by flame atomic absorption spectrometry. The samples were previously
      digested in a mixture of hydrochloric and nitric acid (3:1; aqua regia). Results
      The results show, with respect to road sediment closest to the size that could be
      potentially inhaled from the point of view of public health (<= 10 um), that the
      metal concentrations on average tend to increase in dry weather (29 %). In this
      regard, the concentrations during these time periods are on average 1.69 times
      higher than the lowest limit value set by the reference legislation. However, it
      is suggested that the metal concentrations are mostly due to the use of the land
      rather than weather conditions. Conclusions The findings are a reference point in
      Colombia for the discussion and publication of environmental regulations
      associated with the protection of human health from heavy metals and for
      visualizing future lines of research about the effect of climate change on metal
      concentrations in urban environments.

PMID- 28453087
TI  - [Breathing contaminated air is as harmful as cigarette smoking].
AB  - Objective We want to determine: ?Which of the two factors is more harmful? ?What
      is the magnitude of its effect? and ?What happens when someone is exposed to both
      factors at once?. Methods An ecological study that evaluates the epidemiological
      association (relative risk) between air pollution and smoking with lung functions
      as assessed by functional spirometry in 489 adults. We compare two environments
      with different pollution levels 30 and 60 g/m3 of particulate matter (PM10) and
      groups of smokers against nonsmokers. Results Lung function is impaired (FEV1 <80
      %) in smokers at higher rates than the non-smokers, with an excess risk of 52 %
      (RR. 1.52 CI 95 % 1.11 -2.07). People exposed to higher levels of pollution have
      a higher proportion of pulmonary dysfunction than those exposed to less polluted
      environments with an excess risk of 64 % (RR. 1,64 CI 95% 1.19-2.25). When
      subjects are exposed to both factors, that is smokers who also live in
      contaminated environments, the excess of risk reaches 129 % (RR 2.29 CI 95 % 1.45
      3.61). Conclusions People who breathe in polluted environments have impaired lung
      function in a similar magnitude or greater than smokers. Therefore, we could say
      that breathing contaminated air is equivalent to smoking, but sadly it occurs
      against the affected party's will.

PMID- 28453088
TI  - [Challenges for physical therapist's inclusion in primary care: the
      administrators' perspective].
AB  - Objective Study aimed to identify how physical therapists are included in primary
      care (PC), the perspectives of health managers, and the role that the inclusion
      of this professional in the health team plays. Methods Qualitative study
      involving health secretaries of 22 municipalities in southern Brazil. Results 45
      physiotherapists in the region were included in PC. One of these was in the
      Family Health Strategy (FHS), and two were in the Nuclei of Support to Family
      Health (NSFH). 13 administrators cited the physiotherapists as professionals
      solely for rehabilitation; others think that they have formation at a technical
      level. However, in municipalities that have included the professionals in the FHS
      / NSFH, they were identified as important members of the team. Among the
      difficulties of inclusion, the lack of financial resources for hiring was the
      most commonly reported factor. Discussion There is a limited understanding from
      health managers regarding the role of physiotherapists in PC, especially from the
      majority who do not have access to this professional in their family health
      teams. This is because the lack of prioritization in the allocation of budget
      funds is not conducive to the effective inclusion of professionals who are not
      considered by the law as part of the minimum team. The insertion of the
      physiotherapist PC is further limited; a magnification of the look of the
      managers of the possibilities of action of this professional is required,
      including as a health promoter.

PMID- 28453089
TI  - [Caring ability of family caregivers of children with cancer].
AB  - Objective To describe the caring ability of family caregivers of children with
      cancer. Method This is a descriptive, exploratory study with a quantitative
      approach. A sample of 85 family caregivers of children with cancer was taken.
      After a characterization, they respondd to the Caring Ability Inventory adapted
      for family caregivers of people with chronic non-communicable disease. Results
      The family caregivers werecharacterized by age, gender, socioeconomic level,
      education level, family relationship with the care receiver, social support, time
      of experience, and burden of care generated by the degree of the receiver's
      illness. The overall caring ability was described, as well as the ability of each
      dimension, including knowledge, courage, and patience. Conclusions The principal
      family caregivers of children with cancer were mainly the mothers of the children
      with cancer. 70.6 % of them do not possess sufficient ability to take care of
      their children with cancer. 31.8 % of the group had a lower ability level. This
      finding, together with the demands of coping with the fact of having a child with
      cancer, can be a great burden to family caregivers and generate risk for the ill
      children under their care.

PMID- 28453090
TI  - [Distribution of empathetic orientation among dentistry students of Cartagena,
      Colombia].
AB  - Objective To describe the level of empathy of dental students at the University
      of Cartagena. Methods A descriptive, quantitative study on a sample of 360
      students from 1st to 5th year of Dentistry at the University of Cartagena
      (Colombia) during the second academic period of 2012. The Spanish version for
      students (S version) of the Jefferson Scale of Physician Empathy (JSPE) was
      administered to them. The analysis consisted of calculating descriptive
      statistics, the arithmetic mean, and standard deviation of all the factors and
      their corresponding levels. The comparison of means was performed through
      bifactorial analysis of variance model III, with first-order interaction and
      application of the Duncan multiple comparison test. Results Statistically
      significant differences were found for the "year" variables (p<0.005) and gender
      (p <0.001). Lower empathic orientation values were found for 1st year students
      and higher value were found for women. No significance was found in the
      interaction between these two factors (p>0.05). Conclusions Empathic orientation
      values in the dental students assessed were different depending on the level or
      year of study and the student's gender. This may influence the comprehensive
      training promoted by higher education institutions as part of their educational
      projects. It also provides an imperative for the promotion of interpersonal
      skills interpersonal skills among students starting in the first years of their
      training to help improve the quality of health care provided.

PMID- 28453091
TI  - [Reference and counter-reference in oral health: regulation of access to
      specialized dental care centers].
AB  - Objective Based on the system of reference and counter-reference and
      comprehensiveness in oral health care, we aimed to examine ways of refering users
      to Specialized Dental Care Centers (SDCC) and the interface between them and
      Primary Care. Methods This is a cross-sectional study carried out with users and
      dentists of SDCC in a metropolitan region of Northeast of Brazil. Analyses were
      descriptive, and the association test was done with chi-square. Results Six forms
      of entry to specialized service were identified: free demand (13.8 %) and
      reference by the Primary Care dentist (63.2 %) were most frequent. Users referred
      by the basic health unit dentist had more interest in making a counter-reference
      than the others (p<0.001, PR=4.65, 95 % CI: 2.74 to 7.91), while individuals
      without this referral had 1.49 times more difficulty obtaining care (95 % CI:
      1.02 to 2.17). Referral procedures are a decisive factor for counter-references.
      However, the high demand for primary care services and the short supply these
      services can offer in the face of needs make SDCC performance difficult.
      Conclusion The analysis of oral health practices from the perspective of network
      modeling points to the service's need to establish protocols for regulation in a
      bid to improve access to and the quality of care provided.

PMID- 28453092
TI  - [Tuberculin skin test conversion and association with occupation and demographic
      characteristics in workers at San Ignacio University Hospital].
AB  - Objectives To establish the prevalence of positivity and conversion rate of the
      tuberculin skin test in workers of our hospital, and to describe the related
      demographic and occupational characteristics. Materials and Methods An
      observational, descriptive study was conducted in a cohort of hospital workers
      who underwent the tuberculin skin test. The positivity of the test was defined as
      a result of greater than or equal to 10 mm, and conversion was defined as an
      increase of 6 or 10 mm with respect to the initial test. Results Prevalence of
      23.7 % and incidence of conversion of 13.6 % for the major cut-off point of 10
      mm, and 23 % for the lesser cut-off point of 6 mm, was found. The age of the
      subjects was related to the conversion, but there was no relation with
      occupation. Conclusions The probability of tuberculosis transmission in health
      care workers is higher than in the general population. Promotion and prevention
      measures must be implemented to decrease the transmission and to increase
      awareness of tuberculosis related to occupational activities.

PMID- 28453093
TI  - [Experiencing rejection and disappointments from the health system while living
      with chronic pain during aging].
AB  - Objective To describe the experience of older adults with chronic pain in health
      services. Methods Qualitative, grounded theory type study of 25 elderly residents
      with chronic pain in the cities of Medellin and Bogota. In-depth interviews were
      used to collect the data. The analysis was done using the tools of grounded
      theory as layed out by Strauss and Corbin. Results This study reported 5 main
      categories where it is possible to glimpse how the elderly perceive, at first,
      support from members of the medical team when they bothered to seek solutions to
      their health problems. Over time, however, when pain is exacerbated into a
      "crisis", they began to experience the disappointments and suffering associated
      with health systems, as well as recriminations. This leads them to choose the
      option of distancing themselves from the health system. This makes the elderly
      lose trust in doctors and interest in seeking out health services. . Conclusions
      The study provided a description of the experience of older adults with chronic
      pain when accessing health services. They experience the disappointments and
      rejections that are a product of worsening symptom exacerbations. The elderly are
      in need of humanized care that can in one way or another maked their experience
      of chronic pain more bearable.

PMID- 28453094
TI  - [Prevalence of potential drug interactions with azithromycin in Colombia, 2012
      2013].
AB  - Objective To determine the prevalence of potential drug interactions between
      azithromycin and different IA and III antiarrhythmic groups in a national
      database of drug prescriptions in 2012-2013. Methods Retrospective study based on
      a population database of medicine dispensation. Data from patients who received
      azithromycin between January 1, 2012 and June 30, 2013 were extracted along with
      data from patients who received azithromycin in combination with other
      medications shown to cause heart arrhythmias when used concomitantly. Frequencies
      and proportions were established. Results 13 859 patients receiving azithromycin
      alone or in combination with other drugs were identified. The average time of use
      was 4.5 +/- 0.9 days. A total of 702 patients (5.1 %) received azithromycin plus
      19 other potentially risky drugs. The most frequently associated were loratadine
      (77.1 %), diphenhydramine (16.5 %) and amitriptyline (8.1 %). Combinations with a
      single drug were the most frequent (n=533, 75.9 %), predominantly
      azithromycin+loratadine. The maximum number of combined drugs was six (n=2, 0.3
      %). Conclusions Identification of drug prescriptions through population databases
      is an effective way to find potential drug interactions. The frequency of
      potential interactions between azithromycin and other drugs is common in
      Colombian patients. Future research should assess the risk of occurrence of
      adverse cardiac events.

PMID- 28453095
TI  - [Exploring models for the assessment of the economic, social, political, and
      scientific impact of health research].
AB  - Health research produces effects on the health of populations. This document
      approaches the frameworks and the models used by developed countries to assess
      the impact of health research through documentary analysis of research with the
      highest impact. With this, it was possible to identify two guiding axes of
      analysis: one having to do with focus, and the other having to do with emphasis.
      With these, the published models, their uses, their reach, and their origins are
      related. Our study brings awareness to the features they have and the areas in
      which Colombia could implement them. We found that the framework for evaluating
      health research known as the "payback model" is a model for monitoring research
      that tracks the process and research results with multidimensional categorization
      of the impacts of research.

PMID- 28453096
TI  - [Knowledge of and compliance with universal precautions: students dealing with
      biohazards in Brazil and Colombia].
AB  - Objective To assess scales of adherence to universal precautions and means of
      knowledge transmission among healthcare students in Brazil and Colombia. Methods
      We conducted a pilot study to validate the questionnaire that started a cohort
      study. Twenty-six students in Colombia and 25 in Brazil were intentionally
      selected. The participants were comparable in number and sociodemographic
      characteristics in both countries and studied the health professions (medicine,
      nursing and dentistry). The program SPSS version 18.0 was used to create the
      database and to carry out statistical analysis. Results We evaluated a total of
      51 students. They had a a mean (SD) age of 21.78 (2.33), 84.3 % were women, 66.7
      % had white skin, 47.1 % were medical students, and 70,6 % were in their 4th
      year. They answered about sexual habits reporting that 45.1 had only one partner%
      in the last year, 23.5 % did not use protection, and, of those who were
      protected, 45.1 % used a condom. The mean knowledge was 10.88 (+/-0.952) points
      to an expected 9 points; Cronbach's Alpha (alpha) was 0.823. The mean adherence
      to universal precautions (UPs) was 33.69 (+/-3.36) points to an expected 30.75;
      alpha was 0.741. We found a significant difference in knowledge levels (p<0.007)
      between the two countries and in the adherence to PUs by year of study (p<0.001).
      Conclusions Knowledge about means of transmission was good. Adherence to
      universal precautions was acceptable, but low in terms of the use of glasses,
      face masks, and discarding sharp objects. Dentistry students showed the best
      adherence.

PMID- 28453097
TI  - [Description of the process of preparation and response of local health
      authorities facing the introduction of the Chikungunya virus in Colombia, 2014].
AB  - Objective To describe the process of preparation and response of local health
      authorities in key public health issues while facing the introduction stage of an
      unusual virus: Chikungunya in Colombia in 2014. Methods A cross-sectional study
      was conducted using a survey that was developed for this study and sent to Public
      Health coordinators and to the person in charge of vector borne-diseases in the
      country's territorial entities. Results 23 out of the 35 territories at risk from
      the transmission of Chikungunya agreed to answer the survey. A global review of
      the survey scores for each evaluated section shows better performances in the
      areas of knowledge management, comprehensive patient care, epidemiological
      intelligence, and health promotion. According to the results of this study, the
      epidemiological surveillance system during the Chikungunya epidemic had a low
      acceptability and flexibility, possibly contributing to the underreporting of
      cases. Conclusions In general, knowledge and implementation by local authorities
      of the Integrated Health Strategy- EGI (Estrategia de Gestion Integral, by its
      Spanish acronym)- for vector-borne diseases was evident from the themes evaluated
      in this study. However, it is necessary to reinforce the communication of risks,
      laboratory, and outbreak and contingencies management areas faced during the
      introduction of new viruses.

PMID- 28453098
TI  - [Causes of death from breast cancer in Colombia].
AB  - Objective To review the direct causes of death from breast cancer in Colombia
      according to data from death certificates in 2008. Material and Methods We
      reviewed the direct causes of death in patients whose code of underlying cause of
      death was malignant tumor of the breast according to the National Statistics
      Department of Colombia's (DANE from Spanish initials) records of death in 2008.
      Distribution is evaluated by diagnostic code, age, educational level, marital
      status, social security and place of death. Results In women, the main direct
      causes of death were respiratory insufficiency or failure, cardiac arrest,
      multiple or multisystem organ failure, breast cancer and metastatic breast
      cancer. Most of the death codes were C509 and they were issued for women over 50
      years. In men, the most common cause was respiratory failure. Conclusions The
      main denominations listed on death records as a direct cause of death from breast
      cancer were respiratory failure and arrest and cardiopulmonary arrest. However,
      it is evident that this arises from problems in the registry that are the result
      of not following the International Classification of Diseases (ICD-10). Improving
      the quality of death records is required so that all the information given by the
      death certificates can be used more effectively.

PMID- 28453099
TI  - Knowledge, attitudes and practices of prevention for cervical cancer and breast
      cancer among medical students.
AB  - Objective To assess the knowledge, attitudes and practices of medical students
      for health promotion, primary prevention and early detection of breast neoplasm
      and uterine cervical neoplasm, as well as to make recommendations for improving
      the Public Health curriculum at the Universidad de los Andes. Methodology This
      study utilized a survey of medical knowledge, attitudes and practices applied to
      fifth year Colombian medical students attending the Universidad de los Andes in
      the first semester of 2013. Results 64/76 students answered the surveys (response
      rate 84.2 % ): 62.5 % (40/64) and 37.5 % (24/64) response rates from students in
      their ninth and tenth semesters, respectively; and 64.1 % (41/64) and 35.9 %
      (23/64) response rates from female and male students, respectively. Knowledge:
      clinical breast exam (CBE), breast self-examination (BSE) and mammography were
      recommended by 95.3 % (61/64) of students, 96.9 % (62/64) of medical students and
      90.7 % (58/64) of students, respectively. Attitude: the most effective tests to
      reduce mortality in women aged >= 50 years were the Papanicolaou test according
      to 90.6 % (58/64) of students and mammography according to 82.8 % (53/64) of
      students. Practice: 55.0 % (35/64) of students had received training in the
      guidelines and protocols for breast neoplasm and uterine cervical neoplasm
      screening. Discussion To promote early detection of cervical and breast cancer,
      knowledge, attitudes and practices must be improved to enhance clinical practices
      (e.g. Papanicolaou test) and medical student training guidelines or protocols for
      these two cancers. Overall, with induced demand and support from research
      communities and institutions seeking to make these improvements, we collaborate
      to decrease missed opportunities in medical research and Public Health.

PMID- 28453100
TI  - [Characterization and conditions of caregivers to people with severe disabilities
      in Bogota].
AB  - Objective Describe socioeconomic characteristics, functions assumed, and
      perceived morbidity of a group of caregivers to people with severe disabilities
      in Bogota. Materials and Methods Descriptive transversal study with a sample of 2
      557 caregivers to people with severe disabilities in 19 locations in Bogota,
      selected under saturation of information criteria. The instrument,
      Characterization of Severely Disabled Individuals- Caregiver Chapter, was
      designed and subjected to content validity based on expert review. The pilot test
      was carried out subsequently. The validated and adjusted version was applied to
      the sample in the context of interdisciplinary home visits. Each participant
      signed an informed consent form and the complete confidentiality of the data
      supplied has been assured. Results The study found the influence of gender
      variables on the work of caregivers as well as economic insecurity, fragility of
      support networks, self-rated health disorders, high dedication in time to
      informal care activities, and the multiplicity of functions performed.
      Conclusions The wellness and health conditions of caregivers to people with
      severe disabilities show alterations that urge responses, not only in
      professional duties in the light of cultural recognition and the strengthening of
      this work, but also from the field of public action.

PMID- 28453101
TI  - [Conceptualization of knowledge management in medium and high complexity health
      institutions].
AB  - : Objective To identify the familiarization, conceptualization and incorporation
      of employees of medium and high complexity health institutions in the Valle de
      Aburra, Colombia into the strategic knowledge management platform in 2011.
      Methodology Cross sectional study. The study was carried out by applying surveys
      to 224 employees to assess knowledge management. The population included staff
      who working in the Health Providing Institutions (IPS) of high (52) and medium
      complexity (322) in the Valle de Aburra in 2011. RESULTS: In both the public and
      private institutions surveyed, 38.8 % of the respondents said they were not
      familiar with knowledge management. Among those who had administrative training,
      the ignorance was less than among care workers. It was also noted that as the
      level of education increased, knowledge of the concept was greater. A high
      proportion (65.2 % ) of respondents placed the concept in line with the creation,
      organization, storage, retrieval, transfer and application of knowledge
      systematically. 78.7 % of respondents from public institutions said that
      knowledge management was part of the strategic platform of the institution. 58.3
      % from private institutions said the same. Conclusions In general terms the
      concept of knowledge management is not well conceived or familiar to the staff
      working in these institutions. The study confirmed a lack of empowerment in the
      field to promote the development of new ideas and to ensure that they become
      service innovations or processes that contribute to the development of
      institutional knowledge.

PMID- 28453102
TI  - [Sharing and distrusting: street merchants' view of children in street
      situations].
AB  - Objective To understand the meanings, through the description of experiences that
      street merchants have of their interactions with children in a street situation
      in downtown of Medellin in 2013. Methodology Qualitative investigation with
      ethnographic approach. Observations were made in the zone at different times of
      the day. Twelve interviews with street merchants were held in their work places.
      Records were kept in a field journal. Results The street merchants and children
      in street situations share the same space. Both groups try to survive and their
      relationship is mediated by the trust-distrust that is established between them.
      The coexistence generates ambivalent feelings. For the street merchants, children
      in street situations are the result of abandonment by the family, the state and
      society. They live in a hard world in which they are exposed to a series of risks
      that they must face. Conclusion The interaction between street merchants and
      children in street situations is good to the extent that conflicts are avoided,
      establishing norms of coexistence. The element that determines this relationship
      is trust-distrust. In trust, strong affective ties are generated, considering
      each other family. Distrust generates a preventative attitude.

PMID- 28453103
TI  - [Effects of physical activity on women's morphology].
AB  - Objective To analyze the effect of 12 weeks of physical activity on the
      morphology of the women enrolled in the Family Health Program in the city of
      Patos, Paraiba, Brazil. During these weeks, different physical activity programs
      were applied. Methods A quasi-experimental study, in which 28 women were
      analyzed. All were volunteers, aged between 42 and 56 years and divided into
      groups: G1 (n=15, recreational activities) and G2 (n=13, dance activities). For
      data analysis, the Student t-test for independent samples was used with a
      significance level of p<0.05. Results The comparison of body composition
      variables showed no difference between the two groups. However, when the pre- and
      post-exercise moments are compared, it is seen that the two different physical
      activity programs produce significant changes in the morphology of women.
      Conclusion The results indicate that the applied physical activity programs
      produce significant changes in the morphology of women. On the other hand, we
      consider that the comparison between a physical exercise program and recreational
      physical activity program and their effects on the morphology of women could be
      good.

PMID- 28453104
TI  - [Low back pain perception from the prolonged use of a dynamic seat in sitting
      posture].
AB  - Objective To determine whether a tilting system located in the seat of a chair
      allows for performing voluntary macro-repositioning movements of the pelvis in
      order to reduce the perception of pain after a prolonged period in the sitting
      posture. Methods Eight women participated in the experiment. They were asked to
      sit on the chair with the tilting system and the chair without the tilting system
      for sixty minutes on two different days but carried out at the same time of day.
      Discomfort was assessed with the visual analogic scale. Results people used the
      tilting system to do postural changes of macro-repositioning. However, these
      movements were less than the movements done with the body, not using the system.
      Moreover, discomfort perception was the same for each chair. This might be due to
      the fact that total of macro-repositioning movements did not change. Conclusion
      Future research should evaluate the effect of tilting systems that provide macro
      repositioning in a controlled form, not like in this study. Also, it is necessary
      to study if these types of automatic systems contribute to the reduction of the
      discomfort due to a prolonged period in the sitting posture.

PMID- 28453106
TI  - [Psychometric assessment of a brief Modern Racism Scale].
AB  - Objective To find the internal consistency of the Modern Racism Scale (MRS) among
      medical students in Bucaramanga, Colombia. Methods A total of 352 medical
      students, mean age=20.0 years (SD=1.9) reported their attitudes towards Afro
      Colombians; 59.4 % were women. Students completed the 10-item version of MRS.
      Cronbach alpha and McDonald omega were calculated. Exploratory factor analyses
      were done to propose a brief version of the MRS. Results The 10-item version
      showed a Cronbach alpha of 0.48 and a McDonald omega of 0.15. The short version,
      the Brief Modern Racism Scale (BMRS) (items 1, 4, 5, 7 and 8) presented a
      Cronbach alpha of 0.64 and McDonald omega of 0.65. The BMRS showed one salient
      factor responsible of 41.6 % of the total variance. Conclusions A Spanish
      language short version of the MRS shows better psychometric performance than the
      original version. Further study is needed to corroborate these findings or make
      adjustments for Colombian cultural regions.

PMID- 28453105
TI  - [Prevalence of metabolic syndrome in pubertal stages of female students].
AB  - Objective To analyze the prevalence of metabolic syndrome (MS) in pubertal stages
      of female students. Methods Cross-sectional study of 449 school children between
      eight and 18 years, stratified by pubertal stage, body mass index (BMI) and body
      fat percentage (BF %). The MS was classified according to the International
      Diabetes Federation. The analysis by frequency distribution, confidence intervals
      (95 %), Chi-square and odds ratio for associations was performed. Results The
      prevalence of MS was 3.3 % (CI:2 %-5 %) and 2.5 % (CI: 0.1 - 5 %) in pubertal and
      7.9% (CI:3.2 % - 12.6 %) in the post-pubescent, with a significant association of
      this group with MS (X2 = 5.2 [p <0.02]). The odds ratio shows that post-pubescent
      girls (3.3 [CI: 1.2 to 5]) and obese girls (2.1 [CI: 2 - 2.2]) are more likely to
      have MS, indicating significant linear association between BMI and the outcome
      (X2=29.4 [p<0.001]). Pubescent children under 10 years of age with MS had higher
      %G. The prevalent components were altered waist circumference (27.2 % [CI23 %-31
      %]) and low HDL cholesterol (39.6 % [CI 35 % - 44 %]), as well as prevalence of
      systemic hypertension in post-pubertal girls. Conclusions MS begins in the
      pubertal stage, with prevalence in the post-pubertal stage. Excess fat is a
      trigger in children under 10 years of age. Prevention strategies are needed for
      the population of children and adolescents.

PMID- 28453107
TI  - [Evaluation of the quality of air in a surgical center of a hospital in the south
      of Brazil].
AB  - Objective The aim of this study was to evaluate the quality of air in surgical
      centre rooms of a hospital in the South of Brazil. Methods An evaluation of the
      parameters of comfortability (temperature, luminosity, concentration of carbon
      dioxide and relative humidity), microbiological analysis and chromatographic of
      the particulate material present in the filters of air conditioners was carried
      out. Results Regarding the aspects of comfortability, three surgical rooms did
      not present temperature in accordance to the current legislation, but were found
      within the ideal patterns in other environmental factors. In the analysis of
      particulate material, a larger number of fungal bio-aerosols of viscous colonies
      was obtained than filamentous. Conclusion It was found that the main aspects
      related to the quality of air in the hospital being studied are being
      accomplished; however there is a need of modifying building aspects in the
      surgical rooms in order to reduce the possibility of contamination by air and
      decrease the concentration of carbon dioxide in the environment.

PMID- 28453108
TI  - [Phylogenetic analysis of South American sequences of the nonstructural protein-1
      (ns1) of dengue serotype 2 associated with severe clinical bleeding].
AB  - Objective The objective of this in silico study was to compare nucleotide and
      amino acids DENV-2-NS1 sequences isolated from febrile patients, with and without
      disease severity, from different South American countries. Matherials and Methods
      A bayesian MCMC phylogenetic analysis was carried out using 28 complete sequences
      of the gene NS1 of the DENV-2 serotype (1 056 bp), using MrBayes v.3.2.0
      software, with the model SYM+G (2.5 million generations). We also carried out a
      phylogenetic analysis with Neighbor-Joining method (Jukes-Cantor model). In
      addition, the amino acids sequences were aligned and compared with each other,
      using Clustal W included in MEGA v.5.2 software. Results In the amino acids
      sequences associated with bleeding, the most frequent substitution was isoleucine
      -> threonine at posicion 93. These sequences showed a high percentage (94.6 %) of
      amino acid homology in comparison with the percentage of amino acids homology (74
      %) of DENV-2 isolates not associated with bleeding. Five clades were identified
      that group the vast majority of the DENV-2-NS1 sequences analyzed (19/24; 79.2 %)
      with posterior probability values greater than or equal to 58 %. Seven sequences
      (87.5 %) associated with bleeding were phylogenetically related within clades 4
      and 5, the posterior probability values were 58 % and 97 %, respectively.
      Conclusion Neither phylogenetic characteristics nor differences between amino
      acids of the DENV-2-NS1 sequences studied were found that could be associated
      directly with severity of the disease.

PMID- 28453109
TI  - [Detection of transgenic proteins in maize flour marketed in Bogota, Colombia].
AB  - Objective To detect the presence or absence of transgenic proteins derived from
      GM crops in maize flour marketed in Bogota D.C., Colombia. Methods 11 extraction
      protocols for total protein were evaluated in 17 precooked flour, two uncooked
      and three positive controls. Subsequently, the presence of 7 transgenic proteins
      (CP4-EPSPS, Cry1Ab, Cry1Ac, Cry1F, Cry2A, Cry34Ab1 and Cry3Bb1) using commercial
      ELISA kits was determined. Results It was determined that the best protocol for
      total protein extraction was buffer with Triton X-100, which allowed obtaining
      protein concentrations greater than 0.5 mg per gram of flour and does not
      generate interference with the ELISA technique. Four transgenic proteins were
      detected: CP4EPSPS, Cry1F, Cry1Ab and Cry34Ab1 in precooked and uncooked flour
      with percentages varying between 20 and 100 %. Conclusion Seven of the 19 maize
      flours contain traces of transgenic protein (B2,B8,A3,O3,O1,C1 and C2) that
      provide resistance to lepidopterans and coleopterans, and tolerance to glyphosate
      herbicide, (CP4EPSPS- Cry1Ab, Cry1F, Cry34Ab1 and Cry3Bb1). All detected events
      are approved for human consumption in Colombia, according to the Ministry of
      Health and Social Protection.

PMID- 28453110
TI  - [On health research as public policy in Colombia: assessment and perspectives].
AB  - This essay presents some elements of analysis for thinking about health research
      in Colombia as a public policy, something which was formed starting in 1990 with
      the establishment of Science and Technology regulations. A set of institutional
      adjustments was carried out which led to the creation of the National Program of
      Health Science and Technology and the National Council of Health Science and
      Technology. In addition, it led to the institutionalization of calls for research
      proposals as a mechanism for selecting research projects and assigning resources
      in accordance with the needs and priorities of the National System of Science and
      Technology. Since then, there have been no major changes in the public management
      of health research, with the exception of the Health Research Fund, created in
      2001. However, some efforts have been made to develop some capacities and -so far
      unsuccessfully- to formulate a national policy on health research. The Statutory
      Health Act approved in 2015 could be an important opportunity to realize and
      implement this policy decision.

PMID- 28453112
TI  - [Trend and causes of infant mortality in border areas in Colombia from 2005 to
      2011].
AB  - Objective: To evaluate the registered trends and main causes of Infant Mortality
      (IM) in border areas of Colombia between 2005 and 2011. Methodology: Ecological
      study in border areas, developed from the analysis of institutional information
      on IM and its causes, using the list of leading causes of death of infants and
      children by the WHO. For analysis, descriptive statistics and cluster analysis
      techniques were measured using Excel and the R-Project processing software.
      Results: IM decreased steadily in the country and border areas between 2005 and
      2011.The existence of significantly higher numbers in some of the municipalities
      studied was evident. Municipalities with lower IM had significantly higher
      average scores related to congenital malformations, deformations and chromosomal
      abnormalities (conditions originated during the perinatal period), circulatory
      system diseases, digestive system diseases, and tumors and neoplasms. In
      contrast, municipalities with higher IM rates presented higher average scores
      related to endocrine, nutritional and metabolic diseases, infectious and
      parasitic diseases, and respiratory system diseases, many of them considered
      preventable. Discussion: Border areas are affected by economic, political and
      cultural aspects that make them risk zones and generate interest for health.
      Findings reveal inequalities in the IM behavior when compared to the rest of the
      country. Understanding the peculiarities in these municipalities is crucial for
      the health sector to implement strategies and to pose health services that
      adequately meet the needs, and, thus, achieve health equity for these
      populations.

PMID- 28453111
TI  - [Inequalities in the continuity of outpatient care to displaced population in
      Colombia, 2012 - 2013].
AB  - Objective : To establish inequalities in the continuity of outpatient care to
      displaced population diagnosed with depression. Methods: A cross-sectional study,
      based on clinical records, was performed during the period between June 1, 2012
      and June 30, 2013, on population diagnosed with depression and reduced to
      displaced population. The odds ratio was used to associate the type of population
      with the outpatient care control by professionals, adjusted by sex, age,
      affiliation and region. Results: The following information was obtained from 74
      713 records: 3 149 related to displaced population and 71 564 to non-displaced
      population; non-displaced population had 24 % more ambulatory care (OR: 1.24
      p<0.001; CI 1.10 to 1.39), and the advantage was greater when adjusting the
      information to data, based on affiliation to the health system. In the displaced
      population group, men had greater rates of outpatient care compared to women
      (OR:1.40 p<0.001 CI: 1.08 to 1.83). The disadvantage was also high for non
      displaced women (OR:1.26 p<0.001 CI: 1.10 to 1.44). Although these results were
      obtained for outpatient care in mild and moderate depressive patients, severe
      depression was excluded; the first type of depression was diagnosed in 92 % of
      people. Discussion : The performance record showed inequalities in the continuity
      of outpatient care and, despite the improvement of quality, its coverage is still
      incomplete. During the first year of the unified plan for the Health System,
      apparently, the coverage has not achieved to avoid by itself differences in care
      of displaced population. Improvement of records and interoperability is necessary
      for designing health policies with an equitable approach.

PMID- 28453113
TI  - Loss to follow-up in tuberculosis treatment and its relationship with patients'
      knowledge of the disease and other associated factors.
AB  - Objective : To identify factors associated with loss to follow-up in Tuberculosis
      (TB) treatment, including patients' level of knowledge regarding treatment of
      this disease. Methods: 42 loss to follow-up cases and 84 control cases that were
      finishing the sixth month of their first treatment for tuberculosis were selected
      for this study. Primary data were gathered through interviews, while secondary
      data were obtained from the notification form of the disease, between December
      2011 and April 2012. Factors associated with loss to follow-up were analyzed by
      means of a conditional logistic regression multivariate model for matched case
      control groups. Results: No significant differences were observed between loss to
      follow-up cases and controls regarding socioeconomic factors, lifestyle, clinical
      condition, treatment-related behaviors and the access of patients to sources of
      information on TB. In the regression multivariate analysis, significant
      associations with retreatment after loss to follow-up that were detected include:
      scarce knowledge on tuberculosis, lack of adherence to consultation during the
      current treatment, noncompliance with follow-up consultation deadline, smoking
      and HIV negative. Conclusion: When compared to controls, cases undergoing TB
      retreatment after loss to follow-up have less knowledge on the disease, which is
      a sign for the professionals responsible for health education of the need to
      invest more time and efforts in activities that help the patient understand the
      disease and its treatment, as well as to have higher levels of adherence. In
      addition, noncompliance with the follow-up consultation deadline, failure to
      attend consultations during the current treatment and smoking are also factors
      that may be influenced by poor knowledge on the disease, which leads to the
      treatment loss to follow-up.

PMID- 28453114
TI  - [Tuberculosis caused by Mycobacterium bovis in workers of bovine tuberculosis
      sanitation farms in Antioquia, Boyaca and Cundinamarca].
AB  - Objective: To perform classic and molecular epidemiological surveillance of human
      tuberculosis caused by Mycobacterium bovis in bovine supply chains at farms with
      PPD positive bovines in the departments of Antioquia, Boyaca and Cundinamarca
      during a one-year period. Methods: Livestock farms with PPD positive bovines or
      buffalos were visited in the study departments according to information obtained
      in the "Programa Nacional de Tuberculosis bovina" (National program on bovine
      Tuberculosis) released by ICA (Colombian Agriculture and Livestock Institute).
      Data on socio-demographic information and tuberculosis risk factors associated to
      the occupation were collected through a survey applied to all workers at the
      visited farms. Sputum samples were obtained after informed consent. The sputa
      underwent microbiological and molecular testing to identify members of the M.
      tuberculosis complex. Results : Thirty-three livestock farms were visited and
      information of 164 workers from the bovine supply chain was collected. Staying in
      a PPD positive farm for more than a year, ignorance about the disease and the
      presence of possible vectors, like dogs and cats, were identified as possible
      risk factors for developing tuberculosis. No cases of tuberculosis caused by M.
      bovis or M. tuberculosis in workers of the visited farms were found. Conclusion :
      No cases of the disease caused by this zoonotic agent were documented in the
      departments of Antioquia, Boyaca and Cundinamarca.

PMID- 28453115
TI  - [Waterborne diseases and basic sanitation in Colombia].
AB  - Objective : To analyze the relationship of sewerage coverage and wastewater
      treatment with waterborne disease behaviour. Methods: A descriptive retrospective
      study was conducted using secondary sources (document review and information
      available in databases) about basic sanitation coverage, treatment of domestic
      sewage in the country and the prevalence of waterborne diseases during the period
      2008-2014. Results : The country invested USD 1,100 million in the implementation
      of wastewater treatment systems from 2011 until the first half of 2013. However,
      the incidence of waterborne diseases, such as acute diarrheal disease, foodborne
      diseases and typhoid and paratyphoid fever did not decrease during the period
      2008-2014; only hepatitis A registered a decrease. Discussion: Investment in
      water supply and sewerage systems is relevant to improve health conditions of the
      population and to reduce the incidence and prevalence of various health
      conditions; however, it is necessary to address other aspects such as health
      education and social empowerment to address this problem more efficiently.

PMID- 28453116
TI  - [Expectation of Brazilian nurses about the reception held at the primary health
      care].
AB  - Objective: To know the expectations of Brazilians nurses in relation to the
      reception held for them at the Primary Health Care. Method: This is a qualitative
      study based on the social phenomenology by Alfred Schutz. Results: The nurses
      report that the host is something far from their reality, dependent on policy,
      management, population and physical structure of the workplace. Conclusion : The
      findings of this study showed that the reality of care performed by nurses in
      primary health care is characterized by calls for the evaluation of acute
      complaints, and that the solution to the host be ideal, providing changes in the
      relationship between him and the user they require far capabilities of its
      reality, which was called in this study magic output. It was evident that for
      nurses the reorganization of the host and their work process depends only on
      external factors to their actions, forgetting its commitment to provide a
      humanized care and based on the application of its relational competence.

PMID- 28453117
TI  - [Learning about social determinants of health through chronicles, using a virtual
      learning environment].
AB  - Objective: To describe the contributions of a pedagogical strategy based on the
      construction of chronicles, using a Virtual Learning Environment for training
      medical students from Universidad de La Sabana on social determinants of health.
      Methodology: Descriptive study with a qualitative approach. Design and
      implementation of a Virtual Learning Environment based on the ADDIE instructional
      model. Results: A Virtual Learning Environment was implemented with an
      instructional design based on the five phases of the ADDIE model, on the grounds
      of meaningful learning and social constructivism, and through the narration of
      chronicles or life stories as a pedagogical strategy. During the course, the
      structural determinants and intermediaries were addressed, and nine chronicles
      were produced by working groups made up of four or five students, who
      demonstrated meaningful learning from real life stories, presented a coherent
      sequence, and kept a thread; 82% of these students incorporated in their contents
      most of the social determinants of health, emphasizing on the concepts of equity
      or inequity, equality or inequality, justice or injustice and social cohesion.
      Conclusions: A Virtual Learning Environment, based on an appropriate
      instructional design, allows to facilitate learning of social determinants of
      health through a constructivist pedagogical approach by analyzing chronicles or
      life stories created by ninth-semester students of medicine from Universidad de
      La Sabana.

PMID- 28453118
TI  - [Community center for human development: program for African-Colombian families
      based on the participatory action research approach].
AB  - Objective: To describe the process of construction of a program of Primary Health
      Care (PHC) for African-Colombian families in Guapi, Cauca. Methodology :
      Participatory action research (PAR). Results: The PHC program is a collective
      construction between the IAP Group and the Commission for Support and Follow-up
      (CAS), carried out in four phases: 1. Field preparation; 2. Approximation to the
      universe of the African-Colombian families of Guapi; 3. Building the program
      "Center for Human Development: with strength, joy and love we go 'pa'lante'
      families"; and 4. Evaluation and socialization of results. Discussion: The
      collective construction of the program was conducted from the perspective of PHC,
      PAR and the cultural context, where the experts are the community, health
      professionals and institutions who have the ability to examine, reflect and
      participate in the transformation of reality based on their everyday life and
      view of the world. The starting point involves planning, developing and
      evaluating actions in healthy environments, relating not only to the physical
      space, but also to the work with families and community, taking into account
      needs, perceptions, beliefs, and actions towards health. The "Human Development
      Center Community" program allows a process of community participation towards
      achieving healthy environments to improve the health of the African-Colombian
      population, through the active participation of families, community, institutions
      and health professionals who, based on reality and knowledge exchange, generate
      actions directed to health of the large families of Guapi.

PMID- 28453119
TI  - [Dynamics and interactions between the university community and public health
      2.0].
AB  - Objectives: To explore the experiences of a group of participants in a university
      community with the web in general and with digital contents on public health, to
      describe their motivations and to understand how social networks influence their
      interaction with content on public health. Methodology: Qualitative research.
      Deep semi-structured interviews were conducted to understand the phenomenon.
      Results: Five categories emerged after the study: socialization and
      internalization of the cyberculture, social marketing linked to the web and
      public health, culture of fear and distrust, the concept of health, and the
      health system and public health. Conclusions: Participants have internalized the
      web and have given it a strong symbolic capital. The challenges of public health
      2.0 are not only to achieve interaction with users and to get a place in
      cyberspace, but also to fight against the stigma of the "public" and to take
      advantage of the influence of the web on small-world networks to communicate.

PMID- 28453121
TI  - Effect of an educational intervention on the clinical competence for primary
      healthcare of rheumatic diseases in Mexican physicians.
AB  - Objective : To measure the effect of an educational intervention on clinical
      competences for diagnosis and treatment of rheumatic diseases in primary
      healthcare physicians working in the Guadalajara Metropolitan Area, Jalisco,
      Mexico. Methodology: Quasi-experimental study conducted in physicians from two
      primary health care units. The study was carried out in a 40 physicians sample,
      21 in Group "A" (intervention) and 19 in Group "B" (control). The clinical
      competence for diagnosis and treatment of rheumatic diseases was measured in both
      groups by means of an instrument previously designed and validated (Kuder
      Richardson reliability index =0,94). Results: Clinical competence average score
      prior to intervention was 47 for Group "A" and 42 for Group "B", while after the
      intervention it was 72 and 47 respectively, which shows statistically significant
      differences (Wilcoxon test, p<0,05). Conclusions: Clinical competence for
      diagnosis and treatment of rheumatic diseases in primary healthcare physicians is
      low; however, it can be improved by implementing educational interventions based
      on a constructivist approach.

PMID- 28453120
TI  - Physical activity in a rural community in Colombia.
AB  - Objective: To characterize physical activity profiles in a rural community in the
      southwest of Colombia and to identify knowledge gaps on this issue in the
      country. Methods : Cross-sectional study conducted in a rural area in Puerto
      Caldas, Pereira, Risaralda. The population of the study was obtained by
      convenience sampling from people participating in the activities of the Second
      Multidisciplinary Camp for Research and Services (CUMIS, for its acronym in
      Spanish), which was organized by the Colombian Association of Medical Students'
      Scientific Societies (ASCEMCOL, for its acronym in Spanish). The International
      Physical Activity Questionnaire (IPAQ) was used in order to measure and classify
      the physical activity behaviors of this population. Results: Data from 100
      subjects with a mean age of 43+/-18 years were collected. 6 % of the population
      did not perform any kind of physical activity, while 61 % performed vigorous
      physical activity. Men spent more time in doing vigorous and moderate physical
      activity than women did (p<0.05). The World Health Organization (WHO)
      recommendations on physical activity were followed by 72.29 % (n=60) and 82.35 %
      (n=14) of the people with an age of 18 to64 and >=65 years, respectively.
      Conclusion: It is necessary to build up evidence regarding physical activity in
      rural areas in order to implement public policies that promote its practice in
      communities where socioeconomic and health inequities exist. Part of the
      population living in the community where the study was carried out does not
      follow the WHO recommendations on physical activity; therefore, the lack of
      public health interventions is highlighted. A better coherence between
      international resolutions, national public policies and their implementation
      could lead to an increase in practice levels of physical activity.

PMID- 28453123
TI  - [The role of the Constitutional Court on the analysis of contracts of prepaid
      medicine programs].
AB  - Since 1991, when the current Colombian Constitution came into force and the
      Constitutional Court was appointed as its guardian and protector, constitutional
      values have permeated all subjects and areas of law, even those that were
      previously considered as private matters. Prepaid medicine contracts are a good
      example of this phenomenon, since the Colombian Constitutional Court has limited
      individual freedom of contract to private parties -prepaid medical companies- for
      the benefit of final users of this service through "accion de tutela", in order
      to protect the right to healthcare and to prevent some behaviors that violate the
      principle of good faith. The Court has demanded private companies to assess the
      health condition of patients and has prohibited pre-existent and exclusion
      clauses that diminish the responsibilities of said companies. Nevertheless, there
      is a gap in the law regarding the duties of good faith that concern the user,
      which will be addressed in this paper.

PMID- 28453122
TI  - [Caries experience and quality of life of confined teenagers].
AB  - Objective : To evaluate the impact of caries on the quality of life of teenagers
      confined in the Correctional Center of Cordoba, Argentina. Method : A clinical
      examination was conducted to 70 teenagers in order to determine DMFT and the
      necessary treatment. The Oral Health Impact Profile (OHIP-49) was used. Results :
      The study conducted on a sample of 70 teenagers reported that the average of
      elements found in the mouth was 28.1+/-1.53, the DMFT index was 8.9+/-4.75,
      decayed teeth were 7.4+/-4.26, missed teeth were 0.6+/-0.91, filled teeth were
      0,9 +/- 1.97, and that 67.14 % of patients needed rehabilitation treatment. OHIP
      49 showed greater impact on psychological discomfort (52.86 %), functional
      limitation (47.14 %), physical pain (40 %), physical disability (41.43 %), and
      less impact on psychological disability (28.57 %), social disability (21.43 %),
      and disadvantage (22.86 %). Conclusion : Dental caries experience produces an
      average impact on the quality of life of these teenagers, being physical pain the
      most critical factor.

PMID- 28453124
TI  - [Media influence on adolescent alcohol consumption in schoolsin Bogota].
AB  - Objective This study shows perceptions of alcohol drinking (AD) and its
      relationship with the media among adolescents 12 to 14 years old. Methods We
      performed a qualitative study with adolescents 12 to 14 years old from two public
      schools in Bogota (Colombia), using focus groups, semi-structured interviews and
      participant observation as the primary data collection methods. Results The
      participants repeatedly referred to AD in this age group as a highly prevalent
      behavior with a positive valuation. It was also evident that teenagers 12 to 14
      years old have frequent contact with alcohol-related publicity; they remember
      clearly and bring into the conversation many commercials and advertisements from
      TV, fences, posters, and websites from social networks and many brands. For
      participants, all of these advertising methods associate AD with enjoyable topics
      such as soccer, parties and friends. Discussion Our results are consistent with
      quantitative studies showing a high prevalence of AD among Colombian teenagers.
      We present a clear relationship between positive valuations of consumption among
      teenagers 12 to 14 years old, social normalization of consumption and contact
      with alcohol-promoting publicity. Our results question the efficacy of the
      current law regulations on alcohol advertising, and they should be taken into
      account for the design of new public policies on that matter.

PMID- 28453125
TI  - [Perception of state of health and associated factors in older adults].
AB  - Objective To analyze the socio-demographic factors and health services associated
      with the perception of health state in adults the Sociedad San Vicente of
      Medellin, 2011. Materials and Methods Descriptive, primary source study. 104
      elderly adults were surveyed by telephone and were asked about sociodemographic
      characteristics and health services that may be affecting the perception of their
      state of health. Descriptive measures, statistical tests, regression and
      explanatory models were used, and a prevalence ratio with confidence interval of
      95 % was calculated in the analysis. Results Adults surveyed were on average 68
      years old, with primary schooling. Females predominated, being under the
      subsidized regime, and were supported by their families. The younger they were,
      the better the perception of their health, and women, who live in free union and
      those without education have a negative perception of their health state.
      Regarding health services, those suffering two, four or more diseases, not
      receiving treatment, and consulting psychology between two and four months
      perceive a poor state of health. Conclusion 64 % of older respondents perceive a
      good state of health, but to being older, of the female sex, having
      comorbidities, and receiving no treatment and little access to other health
      services is associated with low self-rated health in older adults.

PMID- 28453126
TI  - [Risk of depression and associated factors in older adults. Antioquia, Colombia.
      2012].
AB  - Objective To explore the association between the risk of depression and
      demographic, social and functional aspects of the elderly department of Antioquia
      in 2012. Materials and Methods A cross-sectional study of 4 248 seniors as a
      primary source. Demographic, social and functional characteristics were assessed.
      Crude OR was calculated and adjusted to find association between the risk of
      depression as measured by the Yesavage's Geriatric Depression Scale and other
      variables of interest. Results The risk of depression was associated with age,
      marital status, educational level, smoking and alcohol consumption, as with
      little or no participation in community activities (OR =1.9 , 95 % [1,2,3.0 ],
      the perception of poor quality of life (OR=10.0 , 95 % CI [ 2.0,48.8 ] and loss
      of functional capacity (OR=6.3, 95 % [29, 13.9 ]. Conclusions The risk of
      depression in the elderly is associated with more difficulty relating to their
      physical and emotional environment than to the biological condition of the
      disease. This is a situation that could be prevented if family ties are
      strengthened and with the aim of a more active and functional aging.

PMID- 28453127
TI  - [Differences of occupational biohazard protection risk in relation to company
      size].
AB  - Objective To obtain information on the level of exposure and protection of
      workers to biological agents working in the health sector, farms, meat industry,
      laboratories, sewage treatment plants, food industry and veterinary centers,
      valuing their differences in relation to the size of the company. Method A study
      in which 590 workers belonging to 59 Spanish companies. An initial questionnaire
      with 3 questions was sent to companies and answered by those responsible for
      prevention, and another questionnaire with 34 questions to be answered by exposed
      workers was also sent. Validation was performed by analysis of overall alpha of
      the second questionnaire to assess the internal consistency and reliability of
      Cronbach of the questionnaires. Results The final sample included 518 workers in
      51 companies in which there was exposure to biological agents. The questionnaire
      obtained a Cronbach's alpha greater than 0.7. Significant differences in
      biological risk management work depending on the size of the company (p-value
      <0.05) were found. Conclusions Our results provide an adequate internal
      consistency of the questionnaire. Furthermore occupational exposure to biological
      agents is a factor to be taken into account since it is not fully developed. This
      is because neither businesses nor prevention professionals have tools available
      that allow easy implementation, and, therefore, management of overall biological
      hazards is inadequate.

PMID- 28453128
TI  - [Access barriers to occupational risk coverage in service provision contracts in
      the public health sector in Bogota].
AB  - Objective To identify access barriers to the General System for Occupational
      Risks (SGRL in Spanish) in a group of independent professionals (contracted with
      service provision contraction) in the public health sector in Bogota. Methodology
      Qualitative research (narrative) through interviews of four independent
      professionals of the Secretaria Distrital de Salud (District Health Secretariat),
      4 independent professionals of Tunjuelito Hospital and 3 experts in the field of
      occupational risks. The content analysis paradigm was used for information
      analysis. Results The two institutions of the public health sector in Bogota
      consulted have implemented strategies that facilitate the access to the SGRL for
      independent professionals. However, the interviewed workers and experts
      identified some access barriers membership for independent workers in this
      occupational risk system; among these barriers are the lack of a culture of
      occupation risk prevention, lack of knowledge about laws and the utility of the
      system as well as the non-conception of the SGRL as a fundamental part of the
      social security system of the country. Conclusion It is necessary for the SGRL to
      be recognized as an integral and fundamental part of the country's social
      security. This depends on a cultural construction of the importance of an
      occupational risk system among the state organizations, employers and employees.

PMID- 28453129
TI  - [Self-Reported consumption of illegal psychoactive substances in a street
      inhabitant population from Cali, Colombia].
AB  - Objective To determine the prevalence of self-reported use of illegal
      psychoactive substances in a homeless population of the city of Cali. Method
      Descriptive study of prevalence of period. The target population was 763 homeless
      people registered during 2010 in the database provided by a temporary shelter
      facility in the city of Cali. Statistical analysis was performed using R version
      3.2.0. Research safe according to the resolution 8430 of 1993. Results 76.9 % of
      the homeless population recognizes that they consume some type of illegal
      psychoactive substance (IPAS). The substances with a higher prevalence of use in
      this population were: marijuana (51.2 %), the crack cocaine (44.6 %) and cocaine
      (11.3 %). 28.6 % of homeless people were found to consume IPAS more than three
      times a day and that the main route of administration is smoke (54.7 %). 50% of
      respondents reported having been hospitalized at some time in a rehabilitation
      center. Discussion The results in this study show that the problem of PASI
      consumption significantly affects the population of homeless people, with
      marijuana and crack cocaine being the most commonly used, which is a complex
      situation if the easy access of these substances and the severe physical and
      mental degenerative effects the cause in those who consume them are taken into
      account. Therefore it is necessary to support initiatives aimed at intervening in
      this social phenomenon.

PMID- 28453130
TI  - [Healthy school environments].
AB  - Objective To determine factors that characterizes school environments and their
      relationship with student learning, welfare and health. Method This is a case
      study supported by a comprehensive qualitative paradigm applied to classroom
      ecology. The fieldwork was carried out in six public schools for students in
      economic strata one and two that use computers in virtual classrooms. The
      information was collected through field journals, film recordings, observation,
      and recordings of interviews. The information was analyzed by categories in open
      general and focused cycles. Results The virtual era has enriched the debate about
      the importance of the environment in pedagogical processes. Nonetheless, the
      emergence of new diseases is a risk which students are exposed to. Pollution and
      overcrowding factors prevail in traditional classroom activities, while in the
      computer rooms the environment is healthier. Hence the need to incorporate these
      issues into the curriculum reforms and action plans to guide healthy living of
      schoolchildren and their families. Despite budget constraints, innovative ideas
      and projects were found. Schools have developed free preventive and corrective
      strategies such as workshops, talks and lectures by invited specialists,
      trainees, and students writing theses. They have also introduced controlled
      Internet access. Conclusion The educational community understands that the
      concept of health is at the heart of a comprehensive concept of education. In
      addition, classroom ecology has determining implications for learning and living
      together in pleasant and healthy environments that are incorporated into
      institutional educational projects.

PMID- 28453131
TI  - [Motorized transportation as a pressure on wellness in expanding cities].
AB  - Objective To analyze the pathologies generated by motorized transportation in the
      context of urban expansion. Methodology This is a documental study based in the
      beginning on specialized scientific articles, followed by consultations of book
      sources and databases and, thirdly, in local newspaper articles. In addition, it
      involved a systematic reflection on the judgment of experts in environmental
      health and risk studies. Results 20 diseases, physical and mental, associated
      with motorized transport in the context of urban expansion are shown. We found
      that not only are drivers vulnerable to the risks of transport but children and
      pregnant women are also highly vulnerable groups. Discussion Considering the
      acute and chronic effects of urban sprawl and some social and environmental
      determinants associated with socio- organizational, technological and climatic
      health risks of cities, transportation is the subsystem with the greatest risk
      present in large cities, and main area of opportunity to improve wellness.

PMID- 28453132
TI  - [Achievement of technological and scientific capacity in Physical Therapy
      services of Bucaramanga and Floridablanca].
AB  - Objective To identify the achievement of the condition of technological and
      scientific capacity of a sample of physical therapy and respiratory services from
      the urban area of Floridablanca and Bucaramanga. Methodology A descriptive study
      was performed with a set of samples not based on probabilities out of
      convenience. The sample consisted of four health service provider institutions in
      the town of Floridablanca and three institutions from the urban area of
      Bucaramanga. During the year 2011, two check lists were applied in order to
      verify the fulfillment of standards of habilitation and to find the reasons for
      their non-compliance in some of their requisites. Results Three institutions in
      Floridablanca belong to the first level of care and one to the second level of
      care; the standards with the lowest fulfillments are: Risk follow-up with a
      median fulfillment score of 0 (Range: 0-12); Medical Records of care with a
      median of 9.5 (Range: 0-100) and the standard of priority procedures with a
      median of 18 (Range: 9-27). In Bucaramanga, two institutions belong to the second
      level of care and one to the third level of care. The lowest standards in
      fulfillment were: Medications and devices with zero for one institution, Priority
      procedures with a median of 60 (Range: 0-89) and physical installations with a
      median of 73 (Range: 64-84). Conclusions The results show a non-compliance with
      the essential requisites of habilitation even though these are demanded by the
      territorial organizations in each health department, district, and municipality.

PMID- 28453133
TI  - [Equations for determining bone age and sexual maturation of children and
      adolescents].
AB  - Objective This study had objective develop and validate prediction equations bone
      age and an index of sexual maturity for children 9 to 14 years old male from the
      city of Rio de Janeiro. Methods The study included 400 children and adolescents
      and 300 subjects (75 %) had their results used to develop the equations and 100
      subjects (25 %) for the validation of the same. Applied the method parametric
      regression Stepwise Correlation, being the independent variables consist of
      anthropometric measurements and taking decisions based on the SEE (Standard Error
      of Estimate) combined with regression rate (R) and determination (R2). Results
      The most significant predictor model, accounted for: Age Bone= 0,062 * Height(cm)
      + 0,426 * Id.Cronol. + 0,041 * MassaCorp.(Kg) - 0,390 * Diameter Femur. Secondly,
      it was taken as the dependent variable sexual maturation according to the
      criteria of Tanner (IMT), and in this context was added as an independent
      variable the bone age (IO), calculating the second predictor model under the same
      conditions of acceptability previously mentioned: Maturation Index Tuner (IMT) =
      0,5423 * age estimated bone - 0,0374 * Height(cm) + 0,0388 * MassaCorp.(Kg).
      Conclusions The results obtained by non-invasive methods are a breakthrough in
      medical diagnostics for disease prevention, as well as equations with these
      objectives, a facilitator in guiding the selection and sports.

PMID- 28453134
TI  - [Cultural specific syndromes treated by traditional doctors].
AB  - Objective In the present work we part of the theoretical concepts of
      sociocultural epidemiology to study the culture-specific syndromes that are
      attended by traditional healers in the city of Taxco, Guerrero, Mexico.
      Methodology The study was primarily qualitative. Interview questionnaire was
      designed, and took into account the proposals with respect to sampling in
      qualitative research. Considering the above, we located six renowned traditional
      physicians living in the same town. The questionnaire was applied to these
      people, and included open-ended questions about the characteristics of these
      healers, the causality of the major culture-specific syndromes, treatments,
      preventive measures employed to prevent or mitigate their impact, and the
      consequences that can happen if these imbalances or illnesses are not treated
      with due care. Results The main findings show how cultural epidemiology provides
      an alternative way to analyze these discomforts, which continue to be served by
      ancient physicians who live in the community. Such conditions are basically the
      "evil eye", "empacho", air, sunken fontanelle, shock, envy, bewitchment, blood
      with toxins, "etika", "algodoncillo", "purpura", "milky" infants, and "aquiztle".
      Also disclosed treatments, preventive measures and consequences that can occur if
      such conditions do not take care in advance. Conclusions We have registered
      culture-specific syndromes, treatments, preventive measures, and varied
      consequences if healing is neglected, this is an important part of the structure
      and medical ideology presented in this resort town, located in the Northern
      Region of the Estado de Guerrero, Mexico.

PMID- 28453135
TI  - [Prevalence of temporomandibular disorders in Mexican children with mixed
      dentition].
AB  - Objective To determine and compare with reports in the bibliography, the
      prevalence of temporomandibular disorders with an instrument validated for
      Mexican children with mixed dentition. Methods 150 children, from 8 to 12 years
      of age and of any sex who attended the pediatric stomatology clinic of the BUAP
      (Meritorious Autonomous University of Puebla) were included and evaluated with
      the diagnostic criteria for research on TTM (CDI/TTM) by a researcher who had
      been previously standardized (kappa=0.93). The results contrasted with reports in
      the bibliography. Results The prevalence of TTM was 20.7%. It was predominantly
      muscular (77.4%), though 33.3% showed alteration of the mouth-opening pattern,
      34% showed joint noises (clicks). The most compromised mandibular function was
      chewing (6%). These results contrast with reports in the bibliography,
      specifically in terms of muscle pain sites and headaches, probably explained by
      different instruments used. Conclusion The prevalence of TTM is in contrast among
      different studies. It is necessary to place emphasis on the need to evaluate
      these factors during the childhood and adolescence with validated instruments.

PMID- 28453136
TI  - [Academic stress, desertion, and retention strategies for students in higher
      education].
AB  - A systematic review was performed to specify the characteristics of academic
      stress that affect the mental health of the university population. To do this,
      recent publications regarding academic stress, student desertion, and retention
      strategies were examined. Throughout this text, we present the results of the
      review in terms of the definitions of academic stress, student desertion, and
      retention strategies. In the same way, we examine the interpretative models with
      regard to student desertion and approach retention strategies in higher
      education. We also review retention experiences of several other countries. In
      terms of Colombia, we present aspects related to student desertion and retention
      programs from the point of view of the National Ministry of Education and from
      the experience of some universities with consolidated programs.

PMID- 28453137
TI  - [Social support to women in situation of domestic violence].
AB  - Objective To understand the meanings attributed by health professionals to the
      social support of women in domestic violence situations. Methods We interviewed
      52 professionals from five local health units of the municipality of Santa
      Catarina, Brazil. Data were processed based on the Grounded Theory. Results It
      was shown that the demands are related to the threats of companions and economic
      dependence, which justifies intersectorial referrals and women's inclusion in the
      income and employment generation program. Discussion Given the high demand and
      the health promotion prerogative of Primary Health Care, a greater availability
      of social workers within the Health Strategy is needed. Social support to women
      requires political interest in combining the health care sector with other
      resources available to combat violence.

PMID- 28453138
TI  - [Family characteristics associated with the nutritional status of schools
      children in the city of Cartagena].
AB  - Objective To determine the family characteristics associated with the nutritional
      status of school children in the city of Cartagena. Method A cross-sectional
      study involving a population of 104 384 children aged 6 to 10 in the city of
      Cartagena. Confidence levels were 95 % and prevalence levels were 5.8 % with 2 %
      error. The sample was 544 students. The schools were selected by proportional
      affixation in each of the three locations in the city, for a total of 21 schools.
      Later, the number of classrooms and the list of the students were requested.
      Children from these classrooms were randomly selected to complete the sample in
      each school. The tab and the family APGAR were the instruments used to assess the
      family characteristics as well as their family functionality. For nutritional
      status, anthropometric measurements were taken and evaluated in the WHO Anthro
      Plus program. The information was processed in the statistical package Epi info
      7. Results 53.9 % of students had adequate nutritional status and 46.1 %
      malnutrition. The family characteristics associated with the child malnutrition
      by excess are: the number of family members OR 0.65 (CI: 0.4 -0.9) and family
      income OR 0.53 (CI: 0.3 -0.7). Meanwhile, the malnutrition by deficit was
      associated only with family income OR 2.08 (CI: 1.1 -3.9). Conclusion The
      variables that showed association with nutritional status were: income equal to
      or less than the minimum wage and number of family members.

PMID- 28453139
TI  - [Social and family support to the elderly in urban areas].
AB  - Objective To describe the social and family support networks available to the
      elderly living in urban areas of the municipality of Angelopolis-Antioquia during
      the year 2011. Materials A descriptive transversal study was conductedusing the
      population experience to determine the social support received by the 239 seniors
      in the urban area of Angelopolis-Antioquia. The data was obtained from primary
      sources and univariate and bivariate analysis was conducted. Results Mostly women
      were interviewed (59.8 %) aged between 60 and 74 (66.9 %). The social status that
      appeared with the highest percentage was "married" (47.3 %) though with the
      interviewed women the social status with the highest occurrence was "widow" (40.6
      %). 69,5 % had an elementary school educational level and 16,7 % had no formal
      education at all. 60.3 % were registered in the subsidized program. The support
      from families and friends was qualified as satisfactory. A statistically
      significant connection was found between gender and undertaking different
      activities in free time (value of p=0,004). Conclusions the study indicates that
      loneliness is an aspect that makes the elderly feel unprotected and vulnerable.
      Despite the general feeling of satisfaction regarding family support, some of
      them, especially women, expressed feeling mistreated. The data along with the
      lack of activities for spare time must be taken into account to formulate
      intervention strategies for effective support networks to improve the situation
      of this vulnerable population of the municipality.

PMID- 28453140
TI  - [Relationship between nutritional status and school absenteeism among students in
      rural schools].
AB  - Objective To determine the nutritional status and prevalence of malnutrition and
      overweight in students in rural schools and their relationship with school
      absence rates. Methods Descriptive study carried out in 34 rural schools in
      Anapoima and La Mesa in 2013. A sample of 785 (82.4 %) students was selected by
      convenience sampling. The inclusion criteria were students registered for the
      period 2013 in grades 0-5 (ages 5-16) with parental consent and student assent.
      Weight and height of all subjects were taken. Overall absence rates and illness
      related absence rates were recorded. Results 422 pupils were male (53.8 %) and
      524 (66.8 %) had between 5-9 years old. A lower than average height for age
      occurred in 10.1 %(n=79) of the students. The thinness was recorded at 1.75
      %(n=13), the overweight at 14.3 %(n=112) and the obesity at 4.5 %(n=45) of the
      students. The number of absence episodes per child per year due to any reason and
      due to disease was 5.7 and 1.4, respectively. Stunted growth and overweight
      students had a significantly higher number of absence days compared to students
      with adequate nutritional status (p <0.01). Stunted growth had the highest
      absence rates. Conclusions Malnutrition and obesity coexist in the study area.
      There is a significant relationship between school absence days (both general and
      illness-related) and stunting and overweight in students.

PMID- 28453141
TI  - [Experience of arterial hypertension in the patient-family relationship in a care
      context].
AB  - Objective To understand how the narrative and conversational experience of
      arterial hypertension is configured in the relationships established among
      patients, family members, physicians and researchers-auditors, placing the
      illness in a care context to facilitate the dissemination of wellbeing
      narratives. Method Qualitative research with reflective and contextual
      conversational-narrative design, which involveda patient diagnosed with
      hypertension, his family and two doctors. The methods of constructing information
      was semi structured interviews, reflective observation and literature review. The
      systematization of information was carried out using frameworks designed for that
      purpose. For the interpretation of results, narrative and conversational analyses
      were used. Results In the process of constructing the experience of hypertension
      by family members or the physician, important aspects are not taken into account
      such as: the listening request, a demand for bonding, the experience of illness
      and in this case, the daily experience of old age. In this context, these kinds
      of relationships can lead to discomfort and suffering in the patient's experience
      of the illness. The conversation generated by all stakeholders enables the
      construction of dialogic-reflexive spaces that provide an opportunity to reshape
      relationships and experience of illness Conclusions The construction of contexts
      of care where one can talk and hear about issues without families and doctors
      facilitates the reconfiguration of the experience of illness, allowing for the
      inclusion of family and physicians in the generation of conversational-narrative
      positions. This implies personal and collective agency in order to mobilize and
      organize the resources they have, consistent with the patient's age and
      diagnosis.

PMID- 28453142
TI  - [The dark rooms and the men who have sex with men: making the invisiblevisible].
AB  - : Objective To design an explanatory model of social representations of men who
      have sex with men in the dark rooms of the city of Santiago de Chile during the
      second half of 2012. METHODOLOGY: Exploratory and explanatory qualitative
      research. The theoretical and methodological approach chosen was based on the
      founded theory. Data collection was conducted using in-depth interviews. RESULTS:
      During the first phase of the research open coding was carried out. Codes and
      related categories were identified: conception of the dark room, biosecurity,
      reasons for entering a dark room, valuation of the dark room, sex practices,
      sexual orientation and roles and ways of relating. CONCLUSIONS: The development
      of a public health policy that includes social determinants of health is an
      imperative. Three key points are identified to intervene positively in their
      health: discrimination and social rejection, the absence or reduction of risk
      perception against dark rooms and places for sexual encounters and the need for
      inspection, monitoring and control of such sites.

PMID- 28453143
TI  - [The understanding and implementation of health promotion at higher education
      institutions in Colombia].
AB  - Objective To characterize the implementation and understanding of health
      promotion at higher education institutions in Colombia. Methods A qualitative
      study with an ethnographic approach was carried out at eleven institutions
      selected in five cities. It was conducted through research tools such as an
      exploratory survey, interviews, direct observation and review of documents. The
      information was analyzed considering conceptualizations about health promotion,
      health settings, and health-promoting universities. Results These institutions
      have implemented policies and programs and have undertaken actions like
      education, reorientation of health services, participation and intervention on
      the environment, as well as research and activities with family and community
      outreach. Conclusion At these institutions, different scopes related to the
      development of health promotion were found, i.e. there was a preventive approach
      along with an inter-sectorial outlook with broad extent. Some of the main
      challenges for institutions are the training of professionals as agents of
      change, and fostering health promotion as a process of organizational change.

PMID- 28453144
TI  - [Knowledge and attitudes of medical students on decriminalized induced abortion].
AB  - Objective To explore if the academic exposure to legal abortion affects the
      knowledge and attitudes of medical students. Method To asses this relationship,
      both qualitative and quantitative approaches were performed. We analyzed a
      medical student cohort enrolled in gynecology and obstetrics at two accredited
      universities in Bucaramanga, Colombia during the second half of 2011. Students
      were invited to participate in two anonymous surveys. One survey was conducted in
      the first three weeks of the semester, and the second was done in the last three
      weeks. A quantitative approach was taken by a group interview of two random
      groups of participants. One group was composed of medical students of gynecology
      and obstetrics (fourth year of medicine), and the other group was composed of
      medical students in their last year (internal medical students). Results The
      items pregnancy with risk to the mother's life, or affected by a non-viable fetal
      malformation, or result of rape were recognized and accepted. 46% of the
      participants changed their attitude about legal abortion at the end of the
      semester. Three out of every four participants changed their attitude to accept
      the decriminalized conditions, while one out of every four people had the
      opposite change of opinion. Medical student's don't believe that general
      practitioners are trained to advice patients in these cases. Conclusions
      Educating and training general practitioners in issues related to legal abortion
      may decrease the risk of inadequate medical assessment in cases of legal
      abortion.

PMID- 28453145
TI  - [Factors related to students' eating practices in three universities in Bogota,
      Colombia].
AB  - : Objective To identify and describe eating habits of students from three
      universities in Bogota and factors influencing their adoption. METHODS: Three
      focus groups were formed with an average attendance of 12 students from different
      undergraduate programs, between the ages of 18 and 25. The content of the
      accounts was analyzed and categorized according to the factors influencing the
      selection of food and eating habits. Results Students identified sensory and
      hygiene factors, the cost of food, the availability of food and available time to
      eat as the main factors influencing food selection. We also identified the
      influence of friends and family, among others, in their choices. Students who
      participated reported to prefer food from home, eating most of their meals at
      home and having eating schedules influenced by academic activities. Conclusion
      Although students have knowledge about what is good for them in terms of food, in
      university life, the organization of academic schedule, food availability and
      economic resources show significant influence on their habits and choices.
      Strategies to promote healthy habits in universities should then prioritize the
      control of such barriers.

PMID- 28453146
TI  - [Association between craniofacial structures adolescents and temporomandibular
      disorders].
AB  - Objective To determine the association between craniofacial structures and the
      presence of TMD in adolescents. Material and Methods Cases-control study. 46
      patients aged 10 to 16 years old were evaluated with their respective lateral
      cephalometric X-rays (23 cases and 23 controls matched for age and sex). The TTM
      was evaluated with the research diagnostic criteria for temporomandibular
      disorders (RDC/TMD). Results The comparison between cases and controls of the
      craniofacial structures did not show significant differences, however the lower
      facial height, facial axis and the mandibular plane were slightly higher in the
      group of cases. In the two-way analysis of ANOVA (diagnosis and age), facial
      convexity presented differences between the adolescent with and without
      temporomandibular disorders (p=0,002). Conclusion Craniofacial structures are not
      associated with the diagnosis of TMD in adolescents. However, changes occur in
      relation to the former location of the jaw, resulting in a skeletal pattern class
      II and an elongated shape of the face.

PMID- 28453147
TI  - [Economic assessment in health and environment from control of persistent organic
      pollutants in Colombia].
AB  - : Objective To estimate the economic benefits related to environment and health
      in the context of the implementation of the Stockholm Convention for the control
      of Persistent Organic Pollutants in the country. METHOD: The estimation was
      conducted based on two scenarios: non-compliance with the agreement and
      compliance with the Convention. Gross profit was derived from the difference in
      present value between the health and environmental costs that are assumed in each
      scenario. Results Gross profit by decreasing health costs arising from the
      implementation of the Convention was estimated at USD $ 511 and USD $ 501
      million. By introducing variables such as management costs and agreement on
      potential benefits for access to international markets, the benefits to the
      country were estimated at between USD $1 631 and USD $ 3 118 million. Discussion
      Despite the economic benefits generated by lower expenditure on health for the
      Convention implementation, the costs associated with reducing pollutant emissions
      generated a negative balance, compensated only by the expectation of higher
      revenues for international market access. We consider this initial economic
      assessment an important contribution, but it should be reviewed to include
      valuation methodologies involving other social profitability variables and
      different scenarios for emerging technologies, new scientific knowledge about
      these pollutants, changes in legislation and / or changes in trade agreement
      conditions, among others.

PMID- 28453148
TI  - [Local contexts of drinking-water quality surveillance: Brazil and Colombia].
AB  - Objective This article aims to analyze comparatively the national surveillance
      systems of water quality for human consumption (DWQS) of Brazil and Colombia,
      seeking to understand how practices are organized in these countries, along with
      their limits and possibilities. Methods The National Cross Comparison methodology
      was used with document analysis of secondary sources, with the purpose of
      discussing the similarities and differences between the two systems using the
      WHO?s Guidelines for Drinking Water Quality. Results The legal framework on DWQS
      in Brazil and Colombia was defined in the 70s and 80s, coinciding with the
      international visibility of this issue. Thereafter, DWQS practices in Brazil have
      been defined and organized in a national program, which has only recently started
      in Colombia. The current Brazilian and Colombian legislations show progress in
      technical elements that guide surveillance practices, such as the incorporation
      of risk assessment methodologies. The Colombian legislation defines the
      regulation of water supply services provision, which is not contemplated in
      Brazilian legislation. Elements such as decentralization, intersectionality,
      universality and right to information are included in the legislations of both
      countries, although further action on DWQS is needed. Conclusions Brazil and
      Colombia have similarities in the implementation of DWQS, despite being at
      different points in the implementation timeline. Actions on drinking-water
      quality surveillance are necessary to guarantee human rights related to the
      protection of the environment, such as universal access to drinking water,
      contributing to the promotion of health.

PMID- 28453149
TI  - [Barriers to sexual health care in Argentina: perception of women who have sex
      with women].
AB  - Objective The objective is to describe the barriers to sexual health care of
      Women Who Have Sex with Women (WSW) in Argentina during 2013. Methods A cross
      sectional, descriptive and quantitative study. An online survey was conducted
      using the Internet, in the period of April-July 2013, with homosexual and
      bisexual women over 18 living in Argentina, making use of the snowball
      methodology. Results A total of 161 women were surveyed. The results showed that
      97.5 % had previously visited a doctor. The doctor did not ask about their sexual
      orientation in 82.8 % of cases. 93.6 % of the surveyed did not receive
      information about STDs; 83.8 % perceive little/no risk regarding STDs. 48.4 % are
      unaware of the methods of protection of STDs among women and 51.6 % obtained this
      information from websites and friends. 77.5 % reported not using protection
      methods. The main reasons were: stable partner, discomfort and the inability to
      acquire them. Discussion The results of this research allow for identifying the
      low perception among WSW regarding STDs, and the difficulty of approaching health
      professionals about this subject.

PMID- 28453150
TI  - [Comparative analysis of the perceptions of HIV/AIDS by gay and bisexual
      Colombian men with and without migratory experience].
AB  - Objective To compare the perceptions about HIV/AIDS of homosexual and bisexual
      Colombian males who live in the Colombian "Eje Cafetero" (Coffee Zone) and of
      those who migrated to Spain, in order to investigate whether those perceptions
      have an influence on the social vulnerability of the groups involved, which is
      determined by aspects such as inequalities that may emerge from ignorance about
      cultural and sexual diversity of the people who are undergoing a migratory
      process. Methods This research has a transnational character and was carried out
      by way of in-depth interviews of adult males living in the autonomous communities
      of Madrid, Valencia, Cataluna and Andalucia in Spain, and in the departments of
      Caldas, Quindio, Risaralda and Valle del Cauca in Colombia between 2011 and 2013.
      In total, 87 interviews were performed in both countries. Conclusion The
      relationship between migration and sexuality must be contemplated from a
      comprehensive viewpoint that enriches understanding both of the society of origin
      as well as of the welcoming country through a consideration of social and
      cultural aspects. Any health promotion and prevention program expecting to have
      an influence on social aspects must take into account people's particularities in
      order to avoid generalizations and their exploitation, recognizing them and
      making them visible as individuals with full rights who express opinions, speak
      and participatevisible as whole right individuals, who express opinions, speak
      and participate.

PMID- 28453151
TI  - Obesity and lifestyle risk factors among an adult population in Legal Amazon,
      Mato Grosso, Brazil.
AB  - Objective To evaluate the frequency of obesity and lifestyle risk factors in the
      population of Barra do Garcas, Legal Amazon. Methodology A randomized,
      transversal study with 305 adults of both genders was performed. Weight, height,
      body mass index (BMI), waist circumference, food dietary habits, frequency of
      smoking and alcoholic consumption, practice of physical activity, and the
      physical activity level were evaluated. Results Smoking and alcoholic consumption
      was higher among men compared to women. Almost 60 % of men engaged in leisure
      time physical activities, whereas only 42.4 % of women practiced physical
      activity. Women were engaged in mostly sedentary behavior activities, such as
      watching television and using the computer use than men. Dietary daily intake of
      fruits and vegetables were higher among women compared to men (65.9 % and 51.5 %,
      respectively). Men were more prone to drink soft drinks than women. However, 39.4
      % of men and only 3.4 % of women drank soft drinks three or more days per week.
      The prevalence of overweight and obesity according to body mass index (BMI) was
      higher in this study. 34.4 % of men and 33.7 % of women were overweight and 15.10
      % and 17.50% of men and women, respectively, were classified as obese. Elevated
      values of waist circumference were found in 35.35 % of men and 70.73 % of women.
      Conclusion Women were more sedentary than men and had higher prevalence of
      abnormal waist circumference values.

PMID- 28453152
TI  - [Effects of acute exercise with upper body cycle ergometer in individuals with
      morbid obesity].
AB  - Objective The purpose of this study is to research effects of acute exercise with
      cycle ergometers adapted for the upper limbs on physiological markers in the
      morbidly obese. Methods Ten morbidly obese patients participated in the study.
      They were submitted to thirty minutes of continuous activity on a cycle ergometer
      adapted to the upper limbs. The following physiological markers were evaluated:
      systemic arterial pressure, heart rate, the double product, and oxygen
      saturation. For the statistical analysis, descriptive analysis was used. Results
      Patients showed a Body Mass Index (BMI) value of 52.1 +/- 8.3. Most of the
      subjects showed a slight reduction in systolic blood pressure (SBP) and diastolic
      blood pressure (DBP) after physical activity, with SBP before and after physical
      activity of 135.5+/-11.4 and 133.5+/-15.3 mmHg, respectively, and, for DBP, 83+/
      7.5 and 77+/-7.1 respectively. The average heart rate was 68+/-10.4 bpm before,
      100.6+/-16.5 bpm during and 80.7+/-14.5 bpm 1 minute after. The double product
      (DP) had a mean increase of 29.6+/-17.1 % in men and 10.4+/-8.9 % in women when
      compared with the initial phase. The oxygen saturation showed no mean difference
      before, during or after activity. Conclusion It can be concluded that acute
      physical exercise with an upper limbs cycle ergometer in morbidly obese patients
      does not represent an elevated risk to these patients, being in fact a good
      intervention to promote health.

PMID- 28453153
TI  - [Evaluation of environmental conditions: air, water and soil in areas of mining
      activity in Boyaca, Colombia].
AB  - Objectives To determine concentrations of PM10, mercury and lead in indoor air of
      homes, water sources and soil in municipalities near mining operations. Method 6
      points were evaluated in areas of influence and 2 in control areas. For
      measurements of indoor air, we used the NIOSH 600 method (PM10), NIOSH 6009
      (mercury) and NIOSH 7300 (lead). For water analysis we used the IDEAM Guide for
      monitoring discharges. For soil analysis, we used the cold vapor technique
      (mercury) and atomic absorption (lead). Results In almost all selected
      households, the average PM10 and mercury concentrations in indoor air exceeded
      applicable air quality standards. Concentrations of lead were below standard
      levels. In all water sources, high concentrations of lead were found and in some
      places within the mining areas, high levels of iron, aluminum and mercury were
      also found. In soil, mercury concentrations were below the detection level and
      for lead, differences between the monitored points were observed. Conclusions The
      results do not establish causal relationships between mining and concentration of
      these pollutants in the evaluated areas because of the multiplicity of sources in
      the area. However, such studies provide important information, useful to agents
      of the environmental health system and researchers. Installation of networks for
      environmental monitoring to obtain continuous reports is suggested.

PMID- 28453154
TI  - [Patients' knowledge and practices about unconsumed drugs disposal. An Approach
      to Ecopharmacovigilance].
AB  - Objective To describe knowledge, attitudes and practices about remaining drugs
      (RD) and expired drugs (ED) disposal. Method Descriptive study in 392 patients at
      a hospital in Bogota, Colombia. Results Participants were 17 to 86 years old.
      66.1% of them had RD, 31.4 % were nervous system drugs (according to Anatomical
      Therapeutic Chemical classification of WHO). 25.8 % of people dispose of RD in
      common waste (CW) and 64.0 % dispose of ED in CW. 17.4 % think RD, and 62.5 %
      think ED should be thrown away like CW. 4.9% of people think RD, and 6.6 % think
      ED should be thrown away in specialized places. 92.4 % people don't know about
      DRP nor 86.7 % about "Puntos Azules"; 94.6 % would like more information. 79.1 %
      think that throwing away drugs can affect health and, 88.8 %, the environment.
      Conclusions Most participants dispose of drugs inappropriately. They think that
      it is wrong and this can damage the environment and health. There is an interest
      in being informed. This reveals an area of possible work in awareness,
      information and education from pharmacovigilance about this subject for the
      benefit of the population.

PMID- 28453155
TI  - Incorporating equity issues into the development of Colombian clinical practice
      guidelines: suggestions for the GRADE approach.
AB  - Objective To propose how to incorporate equity issues, using the GRADE approach,
      into the development and implementation of Colombian Clinical Practice
      Guidelines. Methodology This proposal was developed in four phases: 1. Included a
      literature review and the development of a preliminary proposal about how to
      include equity issues; 2. Involved an informal discussion to reach a consensus on
      improving the first proposal; 3. Was a survey of the researchers' acceptance
      levels of the proposal, and; 4. A final informal consensus was formed to adjust
      the proposal. Results A proposal on how to incorporate equity issues into the
      GRADE approach was developed. It places particular emphasis on the recognition of
      disadvantaged populations in the development and implementation of the suggested
      guideline. PROGRESS-Plus is recommended for use in exploring the various
      categories of disadvantaged people. The proposal suggests that evidence be rated
      differentially by giving higher ratings to studies that consider equity issues
      than those that do not. The proposal also suggests the inclusion of indicators to
      monitor the impacts of the implementation of CPGs on disadvantaged people.
      Conclusions A consideration of equity in the development and implementation of
      clinical practice guidelines and quality assessments of the evidence would
      achieve more in the participation of potential actors in the process and reflect
      on the effectiveness of the proposed interventions across all social groups.

PMID- 28453156
TI  - [The need for clinical guidelines for the comprehensive management of patients
      with cleft lip and palate].
AB  - Objective To identify clinical guidelines for the treatment of cleft lip and / or
      palate in children under one year of age, published in Colombia and
      internationally. Method A search was conducted in three databases: PubMed, Lilacs
      and Scielo with the terms "guideline cleft lip and palate", "protocols cleft lip
      and palate", "guia clinica labio paladar fisurado", "guia de manejo labio paladar
      fisurado" and "guia labio paladar hendido". In addition to this, we consulted the
      websites of all pediatric hospitals in Colombia. Results 190 papers were found,
      of which 96 were not related to the population or focused on treatment, 84 were
      disciplinary, 8 interdisciplinary and only two were clinical guidelines.
      Conclusions There are few published guidelines and there is a lack of unified
      criteria. This gives rise to numerous forms of intervention and the creation of
      interdisciplinary teams. Therefore, there is a need to reach a consensus
      regarding the therapeutic approach in order to create treatment protocols based
      on evidence with quality standards.

PMID- 28453157
TI  - [Seroprevalence of antibodies to measles, rubella, mumps, hepatitis B viruses and
      all three poliovirus serotypes among children in Quindio, Colombia].
AB  - Objective The main goal of this research was to assess the seroprevalence of
      antibodies against measles, rubella, mumps, hepatitis B and all three poliovirus
      serotypes among children in the Quindio Department, Colombia. Methods Blood
      samples were obtained from 170 healthy children aged 5-9 years from nine
      municipalities in Quindio. The presence of serum IgG antibodies against measles,
      rubella, mumps and Hepatitis B were determined using commercial indirect ELISA
      kits. Immunity to poliomyelitis was assessed through the presence of neutralizing
      antibodies following the method recommended by the World Health Organization.
      Results Among the 170 children enrolled, 169 (99.41%), 170 (100 %), and 167 (98.2
      %) were seropositive to poliovirus 1, poliovirus 2, and poliovirus 3,
      respectively. The average reciprocal antibody titers were 178 for poliovirus type
      1, 120 for type 2 and 56 for type 3. Of the 170 children, 96.47 % were protected
      against mumps and rubella, and 86.47 % against measles. Only 106 (62.35 %) of the
      studied subjects were proved to be seropositive to hepatitis B. Conclusion The
      immunization program in Quindio has provided seroprotection against all three
      poliomyelitis serotypes, rubella and mumps. However, the child population is not
      fully protected against measles and hepatitis B virus infections.

PMID- 28453158
TI  - [Costs of infection associated with urinary bladder probes in a teaching hospital
      in Santander, Colombia].
AB  - Objective To estimate the excess costs of urinary tract infection associated with
      catheter use and clinical interventions that influence costs the most. Methods A
      study of cohorts paired by the time of occurrence of the nosocomial event was
      carried out. Those exposed were patients with urinary tract infection associated
      with catheters and those unexposed were patients without nosocomial infection,
      admitted with a similar diagnosis. In both cohorts the direct costs of hospital
      care were evaluated. Results Excess total cost of care for a urinary tract
      infection associated with catheter was 2 460 168 (Colombian pesos in 2009). The
      highest percentage (71.8 %) was attributed to the days of hospitalization in the
      general ward; daily valuations contributed 19.1%, followed by antibiotics (6%),
      blood cultures (5 %), arterial blood gases (2 %). The remaining cost categories
      contributed less than 1 % each. Discussion This study tried to get closer to the
      actual cost, using variables such as ultrasound, arterial blood gases and others
      unused in previous studies in addition to the common variables such as length of
      hospital stay, and consumption of antibiotics. To our knowledge this is the first
      study of micro costs of nosocomial infections that has been done in the country,
      using a cohort as a design. Conclusion It was found that urinary tract infection
      associated with catheter use had a direct excess of costs of 2 460 168 Colombian
      pesos (US$ 1 329 dollars in 2009) It was found that urinary tract infection
      associated with catheter had a direct excess of costs of 2 460 168 Colombian
      pesos (US$ 1 329 dollars in 2009).

PMID- 28453159
TI  - Intestinal parasites in children and soil from Turbaco, Colombia and associated
      risk factors.
AB  - Objective To determine the frequency of intestinal parasites in children and soil
      from Turbaco- Colombia and associated risks factors. Methods Analytical study in
      which 390 children between 2 and 12 years old from 10 neighborhoods of Turbaco
      were included, whose legal representatives gave informed consent. Three serial
      samples of feces and 10 soil samples were processed. Risk factors were determined
      through an interview. Physicochemical and structural characteristics of soils
      were also evaluated. Results Parasites were found in 30.5 % of children. 162
      parasites were observed; the most frequent protozoan was Endolimax nana (30.3 %)
      and in terms of helminthes, the most frequent was Ascaris lumbricoides (4.9 %).
      No statistical association between age or sex and intestinal parasites (p>0.05)
      or between risk factors and intestinal parasites (p>0.05) was found. Low
      frequencies of intestinal parasites were encountered in soil samples, being more
      common Entamoeba spp., Giardia spp., and Ascaris lumbricoides. Neighborhoods of
      Turbaco had sandy dry soil with low content of ions, low conductivity and low
      organic matter. Conclusion This study showed a low frequency of intestinal
      parasites in feces and soils. Despite this, pathogenic parasites were found which
      can affect the health of the population. Besides this, a high percentage of
      intestinal parasites that are transmitted through feces were detected indicating
      fecal contamination and low level of hygiene.

PMID- 28453160
TI  - [Knowledge, attitudes, practices and education among students in a faculty of
      health].
AB  - Objective To determine tuberculosis (TB) knowledge, attitudes, practices,
      education and Tuberculin Skin Test (TST) positivity among Colombian health
      professions students in their last year of study. Methods A cross-sectional study
      was conducted using a self-reported questionnaire about TB knowledge, attitudes,
      practices and education with 193 students of medicine, nursing, dentistry,
      physical therapy, speech and language therapy, occupational therapy, clinical
      laboratory studies and emergency care. A TST was performed on 153 of the
      students. Results Although most of survey respondents perceived the TB education
      they received to be "sufficient", the results regarding their knowledge of TB do
      not support such perceptions: 35.2% of participants did not identify TB risk
      factors, 33.7 % of participants identified Colombian TB incidence, and only 1.6 %
      identified appropriate initial treatment for TB. In regards to practices, 50 % of
      respondents admitted that they would take care of a patient without a high
      efficiency mask. The TST was positive in 35 % of participants. Conclusions Our
      results show that there are opportunities to improve TB education in this health
      faculty, there is also a need to improve safety practices in the facilities where
      students work in order to reduce their risk of conversion.

PMID- 28453161
TI  - [Prevalence of temporomandibular disorders among industrialworkers. Association
      with stress and sleep disorder].
AB  - Objective To determine the presence of temporomandibular disorders (TMD), sleep
      disorders and stress, as well as the association between these factors, among
      industrial workers in Sao Paulo State, Brazil. Material and Methods Fonseca's
      questionnaire was used to verify the level of TMD, the Toronto Sleep Assessment
      Questionnaire (SAQ) was applied to check the quality and occurrence of sleep
      disorders, and the Social Readjustment Rating Scale (SRRS) was used to check the
      degree of stress. The data collected were tabulated with Epi InfoTM 7 and
      statistically analyzed using the chi-square test, with a 5 % significance level.
      Results 104 workers participated in the survey. Most were male (74 %) between 35
      and 44 years of age (26 %). Thirty-seven (35.6 %) had some degree of disorder, 65
      (62.5 %) presented with sleep disorders, and 6 (5.8 %) presented with higher
      degrees of stress. After statistical analysis, there was no significant
      association between stress and temporomandibular disorders (TMD). However, there
      was an association between quality of sleep and sex of the individual with TMD
      (p<0.01). Conclusion We conclude that a high percentage of the analyzed
      population has sleep disorders and TMD. Sex and the quality of sleep influence
      the occurrence of TMD.

PMID- 28453162
TI  - Transposition of Both Oblique Muscles Combined With Lateral Rectus Botulinum
      Toxin Injection and Globe Fixation Suture in the Treatment of Congenital Cranial
      Nerve III Palsy.
AB  - The authors report a new technique to treat complete cranial nerve III palsy. A
      15-year-old girl underwent botulinum toxin injection into the lateral rectus
      muscle, nasal transposition of both the superior and inferior oblique muscles to
      the medial rectus insertion, and absorbable suture globe fixation to the nasal
      orbital periosteum. Six months postoperatively, her primary position eye
      deviation was within 12 prism diopters of orthotropia with limitation of ductions
      in all directions. [J Pediatr Ophthalmol Strabismus. 2017;54:e13-e17].

PMID- 28453163
TI  - Malignant Ciliary Body Medulloepithelioma With Brain and Parotid Metastasis.
AB  - A 12-year-old girl with malignant ciliary medulloepithelioma and parotid
      metastasis was treated with semi-exenteration of the orbit and external beam
      radiotherapy. She had brain metastasis 7 months later and was treated with
      salvage chemotherapy. The patient was disease free at 11 months of follow-up. In
      aggressive cases, exenteration combined with radiotherapy and chemotherapy are
      necessary for disease control. [J Pediatr Ophthalmol Strabismus. 2017;54:e18
      e22].

PMID- 28453164
TI  - Managing Flap Tears of the Rectus Muscles.
AB  - Traumatic and iatrogenic flap avulsions of rectus muscles are infrequently
      reported. Three cases of rectus muscle flap tears are described demonstrating use
      of appropriate imaging for preoperative diagnosis, intraoperative findings to
      confirm diagnosis, and modalities of surgical management. [J Pediatr Ophthalmol
      Strabismus. 2017;54:e23-e26].

PMID- 28453165
TI  - Intravitreal Ranibizumab Injection in Peripapillary CNVM Related to Idiopathic
      Intracranial Hypertension.
AB  - Peripapillary choroidal neovascular membrane (CNVM) may develop in papilledema
      related to idiopathic intracranial hypertension. The authors present a teenaged
      boy who responded well to one dose of intravitreal ranibizumab injection. [J
      Pediatr Ophthalmol Strabismus. 2017;54:e27-e30.].

PMID- 28453166
TI  - An analysis of the relationship between bodily injury severity and fall height in
      victims of fatal falls from height.
AB  - Aim of the study: One of the basic issues discussed in forensic literature
      regarding falls from a height is determination of fall heights and
      differentiation between suicidal and accidental falls. The aim of the study was
      to verify the usefulness of the available methods for the purposes of forensic
      expertises. Material and methods: The study encompassed fatalities of falls from
      a height whose autopsies were performed in the Department of Forensic Medicine in
      Lublin. Results: Similarly to other authors, the severity of injuries was
      assessed using the <i>Abbreviated Injury Scale </i>(AIS) and injury severity
      score (ISS). The study findings demonstrated a statistically significant
      correlation between the fall height and the severity of injuries according to ISS
      and a statistically significant difference in fall heights between the groups of
      accidents and suicides.

PMID- 28453167
TI  - Evaluation of possibilities of differentiating the causes of fatal falls from a
      height using the Berghaus scale.
AB  - Aim of the study: In Poland, approximately several hundred of individuals die due
      to falls from a height annually; in some cases, it is difficult to determine
      explicitly whether the fall was caused by an accident or suicidal attempt. The
      aim of the study was to verify the usefulness of the 14-point Berghaus scale for
      differentiation of fatal falls from a height resulting from accidents or
      suicides. Material and methods: The study material included the results of post
      mortem examinations of 41 fatalities of falls from a height performed in the
      Department of Forensic Medicine in Lublin, which were confronted with the data
      from the records of prosecutor's proceedings. Conclusions: The analysis of
      materials confirmed high usefulness of the Berghaus score criteria to conclude
      whether the fall was accidental or resulted from suicide.

PMID- 28453168
TI  - Study of laboratory profile in patients with aluminium phosphide poisoning in the
      southwest of Iran from 2010 to 2015.
AB  - Introduction: Aluminium phosphide or rice tablet is one of the most common
      pesticides around the world. The substance releases phosphine gas in the presence
      of water, steam or stomach acid which can lead to poisoning. Phosphine poisoning
      is more about suicide the number of which is increasing day by day. Two-thirds of
      patients lose their lives. The aim of this study was to evaluate the data on the
      clinical epidemiology and laboratory changes in patients poisoned with rice
      tablets. Material and methods: A total of 23 patients poisoned by aluminium
      phosphide who referred to Ahvaz Razi hospital within the period of 2010-2015 were
      studied. The data were analyzed using descriptive statistics and statistical
      tests. Results: The mean age of the patients was 27.2 +/-7.3 years and 60.9% of
      the patients were male. 8.7% of the patients had hyponatremia and 21.7% of the
      patients had hypokalemia. In the majority of cases the amount of sodium and
      potassium was normal. 91% of patients had acidosis and serum bicarbonate was
      reduced in the majority of cases. The average interval between poisoning and
      admission was 1.48 +/-0.76 hours. Conclusions: The pattern to change the
      electrolytes and other laboratory factors could be a good marker of the severity
      of the poisoning and the clinical conditions of the patient, which requires more
      specific research to prove the process.

PMID- 28453169
TI  - Identification of unknown corpses through odontological examination - two case
      reports.
AB  - The presented paper illustrates the significance of dental documentation which
      played a key role in the process of identification of two unknown male cadavers
      by means of dental features examination. Efficient operations of the district
      prosecutor's office, which in both cases provided ante mortem dental
      documentation of a missing person likely to be the victim, led to double positive
      identification. In the first presented case dental examination proved to be more
      effective than genetics and contributed to closure of the identification
      procedures. In the second case it confirmed identity equally with genetics. In
      addition, the paper discusses the basic rules of medical records handling and
      storage.

PMID- 28453170
TI  - Variation in gastric alcohol dehydrogenase and the risk of alcohol dependence.
AB  - Alcohol dependence is both a medical and socioeconomic problem. The disease is
      multifactorial, i.e. its development is attributable to gene-gene and gene
      environment interactions. Multi-centre studies investigating the genetic
      background of alcoholism stress the role of genes encoding enzymes of the ethanol
      decomposition pathway in the human body, particularly alcohol dehydrogenase
      (ADH), in the development of alcohol dependence. Among five classes of alcohol
      dehydrogenases, class I and IV isoenzymes have been found to be associated with
      alcohol dependence. Class IV is of particular interest due to its occurrence in
      the upper gastrointestinal tract, mainly in the stomach. No activity of the
      enzyme has been demonstrated in the liver. Single nucleotide polymorphism (SNP)
      of the gene encoding ADH class IV (ADH7) affects its ethanol-oxidizing activity
      in the gastric lumen, thereby influencing the first-pass metabolism (FPM) of the
      substance. The findings published by various research centres have demonstrated
      that specific SNP changes in the ADH7 gene are of different significance for the
      risk of alcohol dependence according to the population studied.

PMID- 28453171
TI  - Cooperation between law enforcement officers and forensic specialists. Diagnosis
      and possible improvements - a Lithuanian experience.
AB  - The article investigates the characteristics and forms of cooperation between
      criminal investigation officers* and forensic laboratory specialists in pre-trial
      proceedings, as well as practical problems in such cooperation. Recently there
      have been a number of particularly heated debates about the relationship between
      determining a person possessing special knowledge and his/her status in pre-trial
      proceedings. Other discussed aspects include cooperation between entities
      involved in pre-trial proceedings in international contexts. A less intensive
      (albeit equally important) discussion relates to the form and characteristics of
      cooperation between criminal investigation officers on the one hand and
      specialists and experts on the other in investigating criminal acts. Bearing in
      mind the high practical importance and the existing differences in scholarly
      approaches to these issues, the current study concentrates on the forms and
      content of cooperation between law enforcement officers and specialists (experts)
      from forensic laboratories, as well as on problems resulting from such
      cooperation and directions for improvement. The first part of the article
      presents selected views on the definition of a person possessing special
      knowledge currently used in Lithuania** and in a number of other states. In the
      authors' opinion, unification (harmonization) of various notions (definitions),
      terms and statuses of an expert, a specialist and special knowledge should be one
      of the objectives in implementing the vision of the joint European forensic
      science area 2020. Achieving this objective requires a comprehensive analysis of
      standards in law and management in using special knowledge of each state***. The
      second part, supported by empirical study results, discusses practical problems
      of cooperation between a law enforcement officer and a specialist (expert),
      analyzes three basic forms of their cooperation and presents the content of those
      forms: activities at the crime scene, cooperation of the two entities in
      commissioning tests, preparing test materials and actual performance of such
      tests, and finally participation of a specialist in other pre-trial activities.
      This part of the paper also proposes methods of improving the efficiency of such
      cooperation. The third part is based on an evaluation of the study results and
      presents the authors' observations regarding the tendency of improving the
      efficiency of cooperation between law enforcement officers and specialists
      (experts).

PMID- 28453172
TI  - Phenotypic classification of gastric signet ring cell carcinoma and its
      relationship with K-ras mutation.
AB  - We aimed to analyze gastric signet ring cell (SRC) carcinoma subtypes by
      investigating gastric and intestinal phenotypic marker expression, and explore
      the relationship between phenotype and K-ras mutation. Immunohistochemistry was
      performed on 163 SRC carcinoma patient specimens to detect gastric (MUC1, MUC5AC,
      and MUC6) and intestinal (MUC2 and CDX2) phenotypic markers, and tumors were
      classified into gastric (G), intestinal (I), and gastrointestinal (GI)
      phenotypes. DNA was extracted from the formalin-fixed, paraffin-embedded tumor
      samples, and K-ras mutations in codons 12, 13, and 61 were identified using
      polymerase chain reaction-based direct DNA sequencing. G, GI, and I phenotypes
      were observed in 63 (38.6%), 71 (43.5%), and 29 cases (17.8%), respectively.
      Expression of MUC2 was significantly associated with invasion depth and lymph
      node metastasis (P = 0.001 and 0.002, respectively), whereas that of CDX2
      significantly corresponded to tumor size and submucosal invasion (P = 0.004 and
      0.001, respectively). MUC5AC expression was inversely associated with gastric
      wall invasion (P = 0.001). Intestinal phenotypic marker expression was positively
      associated with gastric wall invasion and lymph node metastasis. K-ras mutations,
      all of which were in codon 12, were detected in 20 (12.27%) tumors, were
      significantly associated with the I phenotype, and exhibited an inverse
      relationship with MUC5AC and MUC6 expression. I-phenotype SRC carcinomas should
      be distinguished from those of the G phenotype because of their increased
      malignancy regarding invasion and metastasis, and higher K-ras aberration rate.
      The different K-ras mutation frequencies observed imply distinct genetic
      mechanisms in the carcinogenesis of I- and G-phenotype gastric SRC carcinomas.

PMID- 28453173
TI  - Correlation analysis of serum obestatin expression with insulin resistance in
      childhood obesity.
AB  - Childhood obesity is a serious public health concern condition, as excess body
      fat can negatively affect a child's health. Obestatin is a hormone that regulates
      body weight by suppressing appetite and reducing food intake; fasting obestatin
      level is negatively correlated with basal insulin level. This study aims to
      investigate the role of obestatin in insulin resistance. A total of 54 children
      with simple obesity and 57 healthy controls were recruited. Levels of serum
      insulin, fasting blood glucose, cholesterol, triglyceride, low-density
      lipoprotein, and high-density lipoprotein were measured. Serum obestatin level
      was determined using an enzyme-linked immunosorbent assay. We found that body
      mass index and waist-hip ratio of obese children were significantly higher, while
      obestatin level in the obese group was significantly lower (P < 0.001), as
      compared to those of controls. In addition, obese children exhibited higher
      levels of insulin, total cholesterol, triglyceride, and low-density lipoprotein
      (P < 0.05) as compared to the controls. Fasting blood glucose and high-density
      lipoprotein levels were similar between the two groups (P > 0.05). Leptin level
      in the obese group was also higher (P < 0.05) as compared to that of control
      group. Results showed that insulin resistance index was positively correlated
      with body mass index, waist-hip ratio (r = 0.41, P < 0.001; r = 0.245, P <
      0.001), and triglyceride level (r = 0.25, P = 0.04). Our study demonstrated that
      obestatin is negatively correlated with fasting insulin and leptin levels, and
      positively correlated with insulin resistance in obese children.

PMID- 28453174
TI  - Selection of strawberry cultivars with tolerance to Tetranychus urticae (Acari:
      Tetranychidae) and high yield under different managements.
AB  - Tetranychus urticae Koch (Acari: Tetranychidae) is considered the main pest of
      strawberry. Several factors can favor its development, among them the genotype
      susceptibility and cropping system. The aims of this study were to evaluate the
      agronomic performance of strawberry cultivars under different managements and to
      identify strawberry cultivars that meet tolerance to T. urticae and high fruit
      yield. Thirteen cultivars of strawberry ('Albion', 'Aleluia', 'Aromas',
      'Camarosa', 'Camino Real', 'Campinas', 'Diamante', 'Dover', 'Festival',
      'Seascape', 'Toyonoka', 'Tudla', and 'Ventana') under three managements (open
      field, low tunnel, and high tunnel) were evaluated. The T. urticae attack to
      different cultivars was influenced by managements, being low tunnel the one that
      provided higher infestations in the most evaluated cultivars. 'Camarosa' was the
      cultivar with the lower incidence of pest and 'Dover' had the higher infestation.
      The genotype most suitable for growing under different managements is the
      'Festival' genotype, since it meets tolerance to T. urticae, high fruit yield,
      and phenotypic stability.

PMID- 28453175
TI  - Prevalence of human papillomavirus, Chlamydia trachomatis, and Trichomonas
      vaginalis infections in Amazonian women with normal and abnormal cytology.
AB  - Sexually transmitted infections are an important cause of morbidity among
      sexually active women worldwide, and have been implicated as cofactors in the
      pathogenesis of cervical cancer. We investigated the prevalence of human
      papillomavirus (HPV), Chlamydia trachomatis (CT), and Trichomonas vaginalis (TV),
      and accessed the diversity of HPV in women with normal and abnormal cytology in
      Manaus, Brazil. We used polymerase chain reaction and HPV genotyping by direct
      sequencing. The chi-square test was used to calculate the absolute and relative
      frequencies of the categorical variables, and Fisher's test was used when P <
      0.05. The level of significance was set at 5%. All statistical analyses were
      performed using R 2.9.0. There were statistically significant differences in age
      (P = 0.0395), education level (P = 0.0131), sexual partners (P = 0.0211), condom
      use (P = 0.0039), marital status (P < 0.0001), and pregnancy (P = 0.0003) between
      the normal and abnormal groups. HPV DNA was found in 36.56 and 93.88% of subjects
      in the normal and abnormal groups, respectively. A total of 19 genotypes were
      detected; HPV16 was the most common, followed by HPV58. The percentages of TV and
      CT DNA were 18.04 and 9.02% in the normal group, respectively. The percentages of
      HPV/TV and HPV/CT coinfection were 12.5% each in women with normal cytology.
      These findings improve our understanding of HPV, CT, and TV, and the distribution
      of HPV types, which may be relevant to vaccination strategies for protecting
      women from the north of Brazil from cervical cancers and precancerous lesions.

PMID- 28453176
TI  - Discovery and characterization of new microsatellite loci in Dipteryx alata Vogel
      (Fabaceae) using next-generation sequencing data.
AB  - The use of next-generation sequencing (NGS) technologies provides a great volume
      of genome sequence data even for non-model species. The development of
      microsatellite markers using these data is a relatively quick and easy process.
      Dipteryx alata Vogel (Fabaceae) is an arboreal species from the Cerrado biome and
      is considered an important plant genetic resource. Here, we report the
      development of microsatellite markers for D. alata using NGS data. DNA samples
      from four individuals were sequenced using the Illumina MiSeq platform and high
      quality reads were assembled into contigs of the D. alata genome sequence.
      Microsatellite regions were identified using the IMEX webserver and primer pairs
      were designed using the Primer3 software. The amplification settings for each
      locus were optimized. Fluorescent-labeled primers were developed and used to
      genotype individuals derived from three natural populations of D. alata. Fifty
      four microsatellite regions were identified, from which 27 were elected to primer
      design. Among the amplified loci, 11 were polymorphic, with the number of alleles
      ranging from 2 to 10. The expected heterozygosity under Hardy-Weinberg
      Equilibrium (HWE) per locus varied from 0.191 to 0.807. Genotype and allele
      frequencies for all loci agreed with those expected under HWE and linkage
      disequilibrium was not significant for all pairs of loci. The probabilities of
      exclusion of paternity and of combined identity were equal to 0.993 and 5.65 x 10
      8, respectively. The markers developed in this study are useful to several types
      of population genetic studies with D. alata and, eventually, for closely related
      species.

PMID- 28453177
TI  - Validation of a reaction volume reduction protocol for analysis of Y chromosome
      haplotypes targeting DNA databases.
AB  - The use of Y chromosome haplotypes, important for the detection of sexual crimes
      in forensics, has gained prominence with the use of databases that incorporate
      these genetic profiles in their system. Here, we optimized and validated an
      amplification protocol for Y chromosome profile retrieval in reference samples
      using lesser materials than those in commercial kits. FTA(r) cards (Flinders
      Technology Associates) were used to support the oral cells of male individuals,
      which were amplified directly using the SwabSolution reagent (Promega). First, we
      optimized and validated the process to define the volume and cycling conditions.
      Three reference samples and nineteen 1.2 mm-diameter perforated discs were used
      per sample. Amplification of one or two discs (samples) with the PowerPlex(r) Y23
      kit (Promega) was performed using 25, 26, and 27 thermal cycles. Twenty percent,
      32%, and 100% reagent volumes, one disc, and 26 cycles were used for the control
      per sample. Thereafter, all samples (N = 270) were amplified using 27 cycles, one
      disc, and 32% reagents (optimized conditions). Data was analyzed using a study of
      equilibrium values between fluorophore colors. In the samples analyzed with 20%
      volume, an imbalance was observed in peak heights, both inside and in-between
      each dye. In samples amplified with 32% reagents, the values obtained for the
      intra-color and inter-color standard balance calculations for verification of the
      quality of the analyzed peaks were similar to those of samples amplified with
      100% of the recommended volume. The quality of the profiles obtained with 32%
      reagents was suitable for insertion into databases.

PMID- 28453178
TI  - Seroprevalence of hepatitis E virus among blood donors in Qatar (2013-2016).
AB  - BACKGROUND: Hepatitis E virus (HEV) is an RNA virus transmitted mainly through
      zoonotic transmission or fecal-oral route. More than 80% of Qatar's population
      are expatriates, including many coming from hyperendemic countries; thus, it is
      important to estimate the seroprevalence and to compare between different
      nationalities. The results can be useful in alerting blood banks to the
      importance of HEV screening. STUDY DESIGN AND METHODS: Samples from 5854 blood
      donations provided by Hamad Medical Corporation were tested in the period between
      June 2013 to June 2016. Samples were tested for the presence of anti-HEV
      immunoglobulin (Ig)G and IgM antibodies and viral RNA using real-time polymerase
      chain reaction (PCR). Descriptive statistics, bivariate analysis, and
      multivariate logistic regression were used. RESULTS: Anti-HEV seroprevalence was
      20.7%. A total of 1198 and 38 donations tested positive for IgG and IgM
      antibodies, respectively. Of the IgM-positive donations four tested positive by
      PCR. A significant association was detected between HEV seroprevalence with age
      and nationality. CONCLUSION: The seroprevalence of anti-HEV was high in Qatar.
      Since HEV IgM and RNA were detected, this suggests the possibility of HEV
      transmission by transfusion. Blood banks in Qatar and the region should consider
      screening for HEV, especially when transfusion is intended to pregnant women or
      immunocompromised patients.

PMID- 28453179
TI  - The albatross plot: A novel graphical tool for presenting results of diversely
      reported studies in a systematic review.
AB  - Meta-analyses combine the results of multiple studies of a common question.
      Approaches based on effect size estimates from each study are generally regarded
      as the most informative. However, these methods can only be used if comparable
      effect sizes can be computed from each study, and this may not be the case due to
      variation in how the studies were done or limitations in how their results were
      reported. Other methods, such as vote counting, are then used to summarize the
      results of these studies, but most of these methods are limited in that they do
      not provide any indication of the magnitude of effect. We propose a novel plot,
      the albatross plot, which requires only a 1-sided P value and a total sample size
      from each study (or equivalently a 2-sided P value, direction of effect and total
      sample size). The plot allows an approximate examination of underlying effect
      sizes and the potential to identify sources of heterogeneity across studies. This
      is achieved by drawing contours showing the range of effect sizes that might lead
      to each P value for given sample sizes, under simple study designs. We provide
      examples of albatross plots using data from previous meta-analyses, allowing for
      comparison of results, and an example from when a meta-analysis was not possible.

PMID- 28453180
TI  - A novel homozygous VPS45 p.P468L mutation leading to severe congenital
      neutropenia with myelofibrosis.
AB  - VPS45-associated severe congenital neutropenia (SCN) is a rare disorder
      characterized by life-threating infections, neutropenia, neutrophil and platelet
      dysfunction, poor response to filgrastim, and myelofibrosis with extramedullary
      hematopoiesis. We present a patient with SCN due to a homozygous c.1403C>T
      (p.P468L) mutation in VPS45, critical regulator of SNARE-dependent membrane
      fusion. Structural modeling indicates that P468, like the T224 and E238 residues
      affected by previously reported mutations, cluster in a VPS45 "hinge" region,
      indicating its critical role in membrane fusion and VPS45-associated SCN. Bone
      marrow transplantation, complicated by early graft failure rescued with stem cell
      boost, led to resolution of the hematopoietic phenotype.

PMID- 28453181
TI  - Understanding predictors of continued long-term pediatric cancer care across the
      region: A report from the Consortium for New England Childhood Cancer Survivors.
AB  - BACKGROUND: Many survivors of childhood cancer do not receive recommended
      longitudinal oncology care. Factors present at the time of childhood cancer
      diagnosis may identify patients who are vulnerable to poor adherence to follow
      up. METHODS: This cohort of survivors of acute lymphoblastic leukemia (ALL)
      diagnosed from 1996 to 1999 at seven Consortium for New England Childhood Cancer
      Survivors institutions was evaluated for attendance at oncology clinics at 5 and
      10 years from diagnosis. Demographic, socioeconomic, disease, and treatment
      characteristics were analyzed as risk factors for nonadherence to follow-up.
      RESULTS: Of 317 patients, 90% were alive 5 years from diagnosis and 88% of those
      remained in active follow-up. At 10 years from diagnosis, 88% were alive, 73% of
      whom continued in active follow-up. Insurance status at diagnosis was
      significantly associated with adherence at both 5 and 10 years. At 10 years,
      initial enrollment on therapeutic study was associated with increased attendance
      and central nervous system (CNS) leukemia with decreased attendance. In
      multivariable modeling of follow-up at 5 years, patients who were adults were
      less likely to participate and those with private insurance at diagnosis more
      likely to participate. At 10 years, insurance status at diagnosis remained a
      predictor of adherence to follow-up. CONCLUSIONS: In this regional cohort, many
      patients who are survivors of ALL continue to participate in oncology care at 5
      and 10 years from diagnosis. Factors known at diagnosis including insurance
      status, CNS leukemia, older age, and enrollment on therapeutic study were
      associated with differential attendance to follow-up visits.

PMID- 28453182
TI  - Engineering the Pores of Biomass-Derived Carbon: Insights for Achieving Ultrahigh
      Stability at High Power in High-Energy Supercapacitors.
AB  - Electrochemical supercapacitors with high energy density are promising devices
      due to their simple construction and long-term cycling performance. The
      development of a supercapacitor based on electrical double-layer charge storage
      with high energy density that can preserve its cyclability at higher power
      presents an ongoing challenge. Herein, we provide insights to achieve a high
      energy density at high power with an ultrahigh stability in an electrical double
      layer capacitor (EDLC) system by using carbon from a biomass precursor (cinnamon
      sticks) in a sodium ion-based organic electrolyte. Herein, we investigated the
      dependence of EDLC performance on structural, textural, and functional properties
      of porous carbon engineered by using various activation agents. The results
      demonstrate that the performance of EDLCs is not only dependent on their textural
      properties but also on their structural features and surface functionalities, as
      is evident from the electrochemical studies. The electrochemical results are
      highly promising and revealed that the porous carbon with poor textural
      properties has great potential to deliver high capacitance and outstanding
      stability over 300 000 cycles compared with porous carbon with good textural
      properties. A very low capacitance degradation of around 0.066 % per 1000 cycles,
      along with high energy density (~71 Wh kg-1 ) and high power density, have been
      achieved. These results offer a new platform for the application of low-surface
      area biomass-derived carbons in the design of highly stable high-energy
      supercapacitors.

PMID- 28453183
TI  - Lichen myxedematosus: how to reach the accurate diagnosis.

PMID- 28453184
TI  - Evidence-based interventions for global mental health: role and mission of a new
      Cochrane initiative.

PMID- 28453185
TI  - Generation and optimization of the self-administered pediatric bleeding
      questionnaire and its validation as a screening tool for von Willebrand disease.
AB  - OBJECTIVE: Our objective was to generate, optimize, and validate a self
      administered pediatric bleeding questionnaire (Self-PBQ) as a screening tool for
      von Willebrand disease (VWD) in children referred to the hematology clinic for
      the first time. STUDY DESIGN: The Self-PBQ was generated by combining the
      validated expert-administered PBQ and the International Society on Thrombosis and
      Hemostasis (ISTH) bleeding assessment tool (BAT). Medical terminology was
      translated into lay language requiring a grade 4 reading level. In Phase 1, the
      Self-PBQ was optimized and the level of agreement between the Self-PBQ and the
      expert-administered PBQ was determined. Phase 2 established the normal range of
      bleeding scores (BSs) of the Self-PBQ. Phase 3 examined the Self-PBQ as a
      screening tool for first-time referrals to the hematology clinic. RESULTS: The
      Self-PBQ is a reliable surrogate for the expert-administered PBQ with an
      excellent intraclass correlation (ICC) of 0.917. The Self-PBQ was scored with the
      PBQ and the ISTH-BAT scoring systems, for which its normal BS ranges are -1 to 2
      or 0 to 2, respectively. A positive Self-PBQ BS (>=3) had a sensitivity of 78%, a
      specificity of 37%, a positive predictive value of 0.18, and a negative
      predictive value of 0.91 for identifying VWD in children being investigated by a
      hematologist for a bleeding disorder. CONCLUSION: The Self-PBQ generates
      comparable BSs to the expert-administered PBQ and is a reliable, reasonably
      sensitive screening tool to incorporate into the assessment of children
      presenting to a hematologist for the investigation of an inherited bleeding
      disorder.

PMID- 28453186
TI  - Emergency Physicians Are Able to Detect Right Ventricular Dilation With Good
      Agreement Compared to Cardiology.
AB  - OBJECTIVE: Focused cardiac ultrasound (FOCUS) is a useful tool in evaluating
      patients presenting to the emergency department (ED) with acute dyspnea. Prior
      work has shown that right ventricular (RV) dilation is associated with repeat
      hospitalizations and shorter life expectancy. Traditionally, RV assessment has
      been evaluated by cardiologist-interpreted comprehensive echocardiography. The
      primary goal of this study was to determine the inter-rater reliability between
      emergency physicians (EPs) and a cardiologist for determining RV dilation on
      FOCUS performed on ED patients with acute dyspnea. METHODS: This was a
      prospective, observational study at two urban academic EDs; patients were
      enrolled if they had acute dyspnea and a computed tomographic pulmonary angiogram
      without acute disease. All patients had an EP-performed FOCUS to assess for RV
      dilation. RV dilation was defined as an RV to left ventricular ratio greater than
      1. FOCUS interpretations were compared to a blinded cardiologist FOCUS
      interpretation using agreement and kappa statistics. RESULTS: Of 84 FOCUS
      examinations performed on 83 patients, 17% had RV dilation. Agreement and kappa,
      for EP-performed FOCUS for RV dilation were 89% (95% confidence interval [CI] 80
      95%) and 0.68 (95% CI 0.48-0.88), respectively. CONCLUSIONS: Emergency physician
      sonographers are able to detect RV dilation with good agreement when compared to
      cardiology. These results support the wider use of EP-performed FOCUS to evaluate
      for RV dilation in ED patients with dyspnea.

PMID- 28453187
TI  - PCSK9 monoclonal antibodies for the primary and secondary prevention of
      cardiovascular disease.
AB  - BACKGROUND: Despite the availability of effective drug therapies that reduce low
      density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD)
      remains an important cause of mortality and morbidity. Therefore, additional LDL
      C reduction may be warranted, especially for patients who are unresponsive to, or
      unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein
      convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9
      inhibitors) may further reduce LDL-C, potentially reducing CVD risk as well.
      OBJECTIVES: Primary To quantify short-term (24 weeks), medium-term (one year),
      and long-term (five years) effects of PCSK9 inhibitors on lipid parameters and on
      the incidence of CVD. Secondary To quantify the safety of PCSK9 inhibitors, with
      specific focus on the incidence of type 2 diabetes, cognitive function, and
      cancer. Additionally, to determine if specific patient subgroups were more or
      less likely to benefit from the use of PCSK9 inhibitors. SEARCH METHODS: We
      identified studies by systematically searching the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science. We also
      searched Clinicaltrials.gov and the International Clinical Trials Registry
      Platform and screened the reference lists of included studies. We identified the
      studies included in this review through electronic literature searches conducted
      up to May 2016, and added three large trials published in March 2017. SELECTION
      CRITERIA: All parallel-group and factorial randomised controlled trials (RCTs)
      with a follow-up time of at least 24 weeks were eligible. DATA COLLECTION AND
      ANALYSIS: Two review authors independently reviewed and extracted data. When data
      were available, we calculated pooled effect estimates. MAIN RESULTS: We included
      20 studies with data on 67,237 participants (median age 61 years; range 52 to 64
      years). Twelve trials randomised participants to alirocumab, three trials to
      bococizumab, one to RG7652, and four to evolocumab. Owing to the small number of
      trials using agents other than alirocumab, we did not differentiate between types
      of PCSK9 inhibitors used. We compared PCSK9 inhibitors with placebo (thirteen
      RCTs), ezetimibe (two RCTs) or ezetimibe and statins (five RCTs).Compared with
      placebo, PCSK9 inhibitors decreased LDL-C by 53.86% (95% confidence interval (CI)
      58.64 to 49.08; eight studies; 4782 participants; GRADE: moderate) at 24 weeks;
      compared with ezetimibe, PCSK9 inhibitors decreased LDL-C by 30.20% (95% CI 34.18
      to 26.23; two studies; 823 participants; GRADE: moderate), and compared with
      ezetimibe and statins, PCSK9 inhibitors decreased LDL-C by 39.20% (95% CI 56.15
      to 22.26; five studies; 5376 participants; GRADE: moderate).Compared with
      placebo, PCSK9 inhibitors decreased the risk of CVD events, with a risk
      difference (RD) of 0.91% (odds ratio (OR) of 0.86, 95% CI 0.80 to 0.92; eight
      studies; 59,294 participants; GRADE: moderate). Compared with ezetimibe and
      statins, PCSK9 inhibitors appeared to have a stronger protective effect on CVD
      risk, although with considerable uncertainty (RD 1.06%, OR 0.45, 95% CI 0.27 to
      0.75; three studies; 4770 participants; GRADE: very low). No data were available
      for the ezetimibe only comparison. Compared with placebo, PCSK9 probably had
      little or no effect on mortality (RD 0.03%, OR 1.02, 95% CI 0.91 to 1.14; 12
      studies; 60,684 participants; GRADE: moderate). Compared with placebo, PCSK9
      inhibitors increased the risk of any adverse events (RD 1.54%, OR 1.08, 95% CI
      1.04 to 1.12; 13 studies; 54,204 participants; GRADE: low). Similar effects were
      observed for the comparison of ezetimibe and statins: RD 3.70%, OR 1.18, 95% CI
      1.05 to 1.34; four studies; 5376 participants; GRADE: low. Clinical event data
      were unavailable for the ezetimibe only comparison. AUTHORS' CONCLUSIONS: Over
      short-term to medium-term follow-up, PCSK9 inhibitors reduced LDL-C. Studies with
      medium-term follow-up time (longest median follow-up recorded was 26 months)
      reported that PCSK9 inhibitors (compared with placebo) decreased CVD risk but may
      have increased the risk of any adverse events (driven by SPIRE-1 and -2 trials).
      Available evidence suggests that PCSK9 inhibitor use probably leads to little or
      no difference in mortality. Evidence on relative efficacy and safety when PCSK9
      inhibitors were compared with active treatments was of low to very low quality
      (GRADE); follow-up times were short and events were few. Large trials with longer
      follow-up are needed to evaluate PCSK9 inhibitors versus active treatments as
      well as placebo. Owing to the predominant inclusion of high-risk patients in
      these studies, applicability of results to primary prevention is limited.
      Finally, estimated risk differences indicate that PCSK9 inhibitors only modestly
      change absolute risks (often to less than 1%).

PMID- 28453188
TI  - Description of 15 DNA-positive and antibody-negative "window-period" blood
      donations identified during prospective screening for Babesia microti.
AB  - BACKGROUND: Blood donation screening detecting only antibodies fails to identify
      donors in the earliest stage of infection, before a detectable immunologic
      response, that is, the "window period" (WP). We present data on WP donations
      identified during prospective screening for Babesia microti, a transfusion
      transmissible parasite of increasing concern in the United States. STUDY DESIGN
      AND METHODS: Blood donations collected in Connecticut, Massachusetts, Minnesota,
      and Wisconsin were screened using polymerase chain reaction (PCR) and arrayed
      fluorescence immunoassay (AFIA) to detect B. microti DNA and antibodies,
      respectively. Parasite loads were estimated using quantitative PCR. Red blood
      cell (RBC) samples were inoculated into hamsters to assess infectivity. Donors
      screening reactive were indefinitely deferred, tested by supplemental methods,
      and followed to assess DNA and antibody clearance. Demographic data from WP
      donors (i.e., those screening PCR positive and AFIA negative) were compared to
      data from other positive donors. RESULTS: Of 220,479 donations screened from June
      2012 to August 2016, a total of 700 were positive, of which 15 (2% of positive
      donations or 1 per 14,699 screened donations) were confirmed WP donations. The
      median estimated parasite load in WP donations was 350 parasites/mL, no different
      than AFIA-positive and PCR-positive donors. Parasite loads in RBC samples from WP
      units ranged from 14 to 11,022 parasites/mL; RBC samples from three of 10 (30%)
      WP donations infected hamsters. The mean age of WP donors was 48 years (range, 17
      75 years); three (20%) were female. WP donor demographics did not differ
      significantly from demographics of other donors. CONCLUSIONS: We report one per
      15,000 B. microti WP infections in blood donors in endemic areas, demonstrating
      the importance of nucleic acid testing to mitigate the risk of transfusion
      transmitted babesiosis.

PMID- 28453189
TI  - Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in
      pediatric cancer patients: A focused update.
AB  - This update of the 2013 clinical practice guideline provides clinicians with
      guidance regarding the use of aprepitant and palonosetron for the prevention of
      acute chemotherapy-induced nausea and vomiting (CINV) in children. The
      recommendations were based on three systematic reviews. Substantive changes were
      made to the guideline recommendations including the inclusion of palonosetron to
      the 5-HT3 antagonists recommended for children receiving highly emetogenic
      chemotherapy (HEC) and the recommendation of aprepitant for children 6 months of
      age or older receiving HEC. To optimize CINV control in children, future work
      must focus on closing critical research gaps.

PMID- 28453191
TI  - Naringenin prevents ischaemic stroke damage via anti-apoptotic and anti-oxidant
      effects.
AB  - Apoptosis and oxidative stress are considered to be the major factors associated
      with the development and progression of many ischaemic cerebrovascular diseases.
      Naringenin (NAR) is an abundant flavanone in citrus plants and has been found to
      exhibit anti-oxidant, anti-carcinogenic and anti-apoptotic effects. This study
      aimed to investigate the anti-apoptotic and anti-oxidant effects of naringenin on
      ischaemic stroke. In vitro, cortical neuron cells isolated from the brains of
      neonatal Sprague-Dawley rats were randomly divided into control, oxygen and
      glucose deprivation/reperfusion (OGD/Rep), NAR-L, NAR-M and NAR-H groups. MTT and
      RT-PCR were used for cell proliferation and apoptosis-related proteins analyses.
      The effects of NAR on the Nrf2 signalling pathway were investigated using
      transfection approaches. Differences in mitochondrial dysfunction were analyzed
      by flow cytometry. In vivo, middle cerebral artery occlusion (MCAO) model was
      prepared and neurological defects and the brain wet/dry (W/D) ratio were assessed
      and recorded; apoptosis was measured based on the TUNEL assay. Additionally,
      biochemical indices were detected both in vitro and in vivo. NAR promoted
      cortical neuron cell proliferation, inhibited apoptosis and oxidative stress, and
      regulated the localization of Nrf2 protein (P<.05). Furthermore, silencing and
      overexpression of Nrf2 affected cortical neuron cell proliferation and apoptosis
      (P<.05). In vivo, NAR could alleviate cerebral oedema, improve neurological
      defects, and reduce apoptosis and oxidative stress (P<.05). These findings
      demonstrated that NAR could reduce apoptosis and oxidative stress and that Nrf2
      signalling pathway is involved in this regulatory process. NAR has health
      promoting properties because of its anti-apoptotic and anti-oxidant effects in
      cases of ischaemic stroke.

PMID- 28453190
TI  - Synergistic activity of everolimus and 5-aza-2'-deoxycytidine in medullary
      thyroid carcinoma cell lines.
AB  - Medullary thyroid cancer (MTC) is a tumor highly resistant to chemo- and
      radiotherapy. Drug resistance can be induced by epigenetic changes such as
      aberrant DNA methylation. To overcome drug resistance, we explored a promising
      approach based on the use of 5-aza-2'-deoxycytidine (AZA), a demethylating agent,
      in combination with the mTOR inhibitor everolimus in MTC cells (MZ-CRC-1 and TT).
      This combined treatment showed a strong synergistic antiproliferative activity
      through the induction of apoptosis. The effect of everolimus and/or AZA on genome
      wide expression profiling was evaluated by Illumina BeadChip in MZ-CRC-1 cells.
      An innovative bioinformatic pipeline identified four potential molecular pathways
      implicated in the synergy between AZA and everolimus: PI3K-Akt signaling, the
      neurotrophin pathway, ECM/receptor interaction, and focal adhesion. Among these,
      the neurotrophin signaling pathway was most directly involved in apoptosis,
      through the overexpression of NGFR and Bax genes. The increased expression of
      genes involved in the NGFR-MAPK10-TP53-Bax/Bcl2 pathway during incubation with
      AZA plus everolimus was validated by western blotting in MZ-CRC-1 cells.
      Interestingly, addition of a neutralizing anti-NGFR antibody inhibited the
      synergistic cytotoxic activity between AZA and everolimus. These results open a
      new therapeutic scenario for MTC and potentially other neuroendocrine tumors,
      where therapy with mTOR inhibitors is currently approved.

PMID- 28453192
TI  - Family Emotional Support and the Individuation Process Among Asian- and Latino
      Heritage College-Going Emerging Adults.
AB  - This study examined whether discrepancies in emerging adults' perceptions of
      their own and their parents' value of education were associated with their
      individuation from family, and whether this relationship was mediated by family
      emotional support. A total of 82 Asian- and Latino-heritage emerging adults
      completed a survey assessing their and their parents' value of education, family
      emotional support, and family engagement (our proxy for individuation). As
      predicted, larger discrepancies in the value placed on education were associated
      with less family engagement; this association was mediated by emerging adults'
      perceptions of family emotional support. These findings suggest that family
      emotional support may play an important role in the individuation process of
      Asian- and Latino-heritage college-going emerging adults.

PMID- 28453193
TI  - Are They Listening? Parental Social Coaching and Parenting Emotional Climate
      Predict Adolescent Receptivity.
AB  - Associations linking parenting emotional climate and quality of parental social
      coaching with young adolescents' receptivity to parental social coaching were
      examined (N = 80). Parenting emotional climate was assessed with adolescent
      reported parental warmth and hostility. Quality of parental social coaching
      (i.e., prosocial advice, benign framing) was assessed via parent-report and
      behavioral observations during a parent-adolescent discussion about negative peer
      evaluation. An adolescent receptivity latent variable score was derived from
      observations of adolescents' behavior during the discussion, change in
      adolescents' peer response plan following the discussion, and adolescent-reported
      tendency to seek social advice from the parent. Parenting climate moderated
      associations between coaching and receptivity: Higher quality coaching was
      associated with greater receptivity in the context of a more positive climate.
      Analyses suggested a stronger association between coaching and receptivity among
      younger compared to older adolescents.

PMID- 28453195
TI  - Teen Dating Violence, Sexual Harassment, and Bullying Among Middle School Youth:
      Examining Measurement Invariance by Gender.
AB  - This study investigated measurement invariance by gender among commonly used teen
      dating violence (TDV), sexual harassment, and bullying measures. Data were
      collected from one cohort of seventh-grade middle school students (N = 754) from
      four schools. Using structural equation modeling, exploratory and confirmatory
      factor analyses assessed measurement models and tested measurement invariance by
      gender for aggression measures. Analyses invoked baseline data only. Physical and
      psychological TDV perpetration measures achieved strict measurement invariance,
      while bullying perpetration demonstrated partial strict invariance. Electronic
      TDV and sexual harassment perpetration achieved metric/scalar invariance. Study
      findings lend validation to prior and future studies using these measures with
      similar populations. Future research should increase attention to measurement
      development, refinement, and testing among study measures.

PMID- 28453194
TI  - Trajectories of Substance Use: Onset and Adverse Outcomes Among North American
      Indigenous Adolescents.
AB  - North American Indigenous communities experience disproportionately high rates of
      substance use, abuse, and dependence and their accompanying consequences. This
      study uses group-based trajectory modeling of past-year substance use (alcohol,
      marijuana, and cigarettes) with a longitudinal sample of Indigenous adolescents
      from the northern Midwest and Canada (spanning ages 10-18 years). The early-onset
      trajectory (36.3%) had more adverse psychosocial difficulties at baseline than
      the mid-onset group (38.3%); both trajectories were associated with several
      negative outcomes at the end of the study. The late-onset trajectory (25.3%) did
      not initiate substance use until later adolescence and had far better outcomes at
      the last wave of the study. Timing of onset matters. Prevention efforts should
      begin in late childhood and continue through mid-adolescence.

PMID- 28453197
TI  - Peers Increase Late Adolescents' Exploratory Behavior and Sensitivity to Positive
      and Negative Feedback.
AB  - Adolescents take more risks with peers than when alone. It is not clear how peer
      presence affects adolescents' risky decision making, however. We used the Iowa
      Gambling Task (IGT)-a game used to assess decision making involving risk and
      reward-to examine how peers affect late adolescents' exploration of relevant
      environmental cues, ability to learn from the outcomes (positive and negative) of
      that exploration, and ability to integrate feedback to adjust behavior toward
      optimal long-term outcomes. One hundred and one 18- to 22-year old males (M =
      19.8 years) were randomly assigned to play the IGT either alone or observed by
      peers. Late adolescents tested with observers engaged in more exploratory
      behavior, learned faster from both positive and negative outcomes, and evinced
      better task performance than those tested alone.

PMID- 28453198
TI  - Longitudinal Links Between Discrimination and Civic Development Among Latino and
      Asian Adolescents.
AB  - The transition from adolescence to adulthood is formative for civic development.
      Unfortunately, many adolescents from Latino and Asian backgrounds experience
      discrimination, which can alienate them from civic life. This study employed
      cross-lagged structural equation modeling to test the bidirectional links between
      perceived discrimination and civic beliefs and activism among Latino and Asian
      late adolescents (N = 400, Mage = 17.34, 61% female). Civic beliefs (i.e.,
      believing that the government is unresponsive) and civic activism (i.e.,
      protesting and expressing political opinions) in high school predicted increased
      perceptions of discrimination over time. Perceiving high levels of discrimination
      in high school predicted a decrease in the belief that society is fair over time.

PMID- 28453199
TI  - Sexual Risk-Taking Among Recently Emancipated Female Foster Youth: Sexual Trauma
      and Failed Family Reunification Experiences.
AB  - Foster youth evidence shows elevated rates of risk behaviors, including sexual
      risk-taking (e.g., unprotected sex). Some studies have identified child
      maltreatment, particularly sexual abuse, as a risk for later sexual risk-taking,
      but none have examined how child welfare placement experiences relate to youth's
      sexual risk-taking. This study investigated relations among child maltreatment,
      child welfare placements, and sexual risk-taking among 114 recently emancipated
      female foster youth. Sexual abuse and failed reunifications with parents were
      associated with greater sexual risk-taking. Moreover, dissociative symptoms
      exacerbated the relation between sexual abuse and sexual risk-taking. These
      findings highlight the need for greater consideration of risks associated with
      emancipated youth's sexual risk-taking and for more research to understand how
      youth experience unsuccessful family reunifications.

PMID- 28453196
TI  - Context of First Same-Sex Condom Use and Nonuse in Young Black Gay and Bisexual
      Males.
AB  - Despite high human immunodeficiency virus (HIV) rates among young Black men who
      have sex with men (YBMSM), there are limited data about condom use during first
      same-sex (FSS). This study sought to understand socio-contextual factors of 50
      YBMSM aged 15-19 years that influenced condom use during FSS. Condom use was
      influenced by individual, partner, and community factors. Individual factors
      recent illness or sexually transmitted infections (STI)-prompted condom use,
      while frequent HIV testing prompted nonuse. Partner factors-proactive
      encouragement from partners-prompted condom use, while trust and condom
      discomfort prompted nonuse. Larger community factors-such as presence of females
      were key for use, while limited sexual health information combined with peers who
      discouraged condoms prompted nonuse. A multilevel approach may be useful in
      developing sexual health programming for these young men.

PMID- 28453200
TI  - The Meaningful Roles Intervention: An Evolutionary Approach to Reducing Bullying
      and Increasing Prosocial Behavior.
AB  - Bullying is a problem that affects adolescents worldwide. Efforts to prevent
      bullying have been moderately successful at best, or iatrogenic at worst. We
      offer an explanation for this limited success by employing an evolutionary
      psychological perspective to analyze antibullying interventions. We argue that
      bullying is a goal-directed behavior that is sensitive to benefits as well as
      costs, and that interventions must address these benefits. This perspective led
      us to develop a novel antibullying intervention, Meaningful Roles, which offers
      bullies prosocial alternatives-meaningful roles and responsibilities implemented
      through a school jobs program and reinforced through peer-to-peer praise notes
      that effectively meet the same status goals as bullying behavior. We describe
      this new intervention and how its theoretical evolutionary roots may be
      applicable to other intervention programs.

PMID- 28453201
TI  - Cross-Cultural Measurement Invariance of Adolescent Self-Report on the Pediatric
      Quality of Life InventoryTM 4.0.
AB  - This study evaluated the cross-cultural measurement invariance of the Pediatric
      Quality of Life Inventory version 4.0 (PedsQLTM) among adolescents sampled from
      Bulgaria, Croatia, India, Indonesia, Nigeria, Serbia, and Turkey. The multiple
      indicator multiple-cause (MIMIC) model was used, which allowed controlling of
      demographic variables (i.e., age, gender, and socioeconomic status). Significant
      effects of country on scores within the PedsQLTM domains were observed, with up
      to 17 items showing differential item functioning (DIF) across the countries. We
      did not find support for cross-cultural measurement invariance hypotheses for
      scores on the PedsQLTM adolescent self-report in this study. Researchers should
      use caution in making cross-cultural quality of life comparisons while using the
      PedsQL.

PMID- 28453203
TI  - Adolescents' Socio-Motivational Relationships With Teachers, Amygdala Response to
      Teacher's Negative Facial Expressions, and Test Anxiety.
AB  - The amygdala is essential for processing emotions, including the processing of
      aversive faces. The aim of this multimethodological study was to relate the
      amygdala reactivity of students (N = 88) toward teachers' fearful and angry
      faces, to students' relationship with their teachers. Furthermore, students'
      neural responses during the perception of teachers' faces were tested as
      predictors of test anxiety (controlling for neuroticism as a potential trait
      anxiety effect). Multiple regression analysis revealed that students reporting
      high-quality teacher-student relationships showed stronger amygdala activity
      toward fearful faces, which was related to worry. Furthermore, students with high
      levels of neuroticism tended to perceive their teachers as motivators and showed
      higher amygdala activity toward angry faces, which was related to the measures of
      emotionality.

PMID- 28453204
TI  - Status Perceptions Matter: Understanding Disliking Among Adolescents.
AB  - The emergence of disliking relations depends on how adolescents perceive the
      relative informal status of their peers. This phenomenon is examined on a
      longitudinal sample using dynamic network analysis (585 students across 16
      classes in five schools). As hypothesized, individuals dislike those who they
      look down on (disdain), and conform to others by disliking those who they
      perceive as being looked down on by their peers (conformity). The inconsistency
      between status perceptions also leads to disliking, when individuals do not look
      up to those who they perceive to be admired by peers (frustration). Adolescents
      are not more likely to dislike those who they look up to (admiration). The
      results demonstrate the role of status perceptions on disliking tie formation.

PMID- 28453205
TI  - Association of Demanding Kin Relations With Psychological Distress and School
      Achievement Among Low-Income, African American Mothers and Adolescents:
      Moderating Effects of Family Routine.
AB  - Association of demanding kin relations and family routine with adolescents'
      psychological distress and school achievement was assessed among 200 low-income,
      African American mothers and adolescents. Demanding kin relations were
      significantly associated with adolescents' psychological distress. Family routine
      was significantly related to adolescents' school achievement. Demanding kin
      relations were negatively associated with school achievement for adolescents from
      families low in routine, but unrelated to achievement for adolescents in families
      high in routine. Additional research is needed on poor families and their social
      networks.

PMID- 28453206
TI  - Adolescent Abstention From Delinquency: Examining the Mediating Role of Time
      Spent With (Delinquent) Peers.
AB  - Research consistently identifies a group of adolescents who refrain from minor
      delinquency entirely. Known as abstainers, studying these adolescents is an
      underexplored approach to understanding adolescent minor delinquency. In this
      paper, we tested hypotheses regarding adolescent delinquency abstention derived
      from the developmental taxonomy model and social control theory in 497
      adolescents (283 boys) aged 13-18 comparing three groups of adolescents:
      abstainers, experimenters, and a delinquent group. We found that the relation
      between adolescent abstention and personal characteristics (i.e.,
      conscientiousness and anxiety) was (partially) mediated by the amount of time
      spent with peers. Furthermore, the level of best friend delinquency moderated the
      relation between time spent with peers and delinquency abstention. Results
      support aspects of both theoretical frameworks.

PMID- 28453207
TI  - Forced Sexual Experiences and Sexual Situation Self-Efficacy Among South African
      Youth.
AB  - Nearly 20% of South African youth experience forced or coerced sexual
      intercourse. Understanding the factors associated with forced sex is important
      for informing prevention programs aimed at reducing sexual violence and HIV and
      AIDS. Multilevel regression models test the association between sexual situation
      self-efficacy and forced sex among 2,893 South African adolescents. Findings
      suggest that youth are more likely to experience forced sex after periods of time
      when their levels of self-efficacy are lower than their average levels of self
      efficacy. Furthermore, youth who are lower on their self-efficacy compared to
      their peers are more likely to experience forced sex. Implications for prevention
      research are discussed.

PMID- 28453208
TI  - Ethnic Identity, Stereotype Threat, and Perceived Discrimination Among Native
      American Adolescents.
AB  - In this study, ethnic identity, stereotype threat, and perceived discrimination
      were examined in relationship to academic achievement and hopelessness in a
      sample of 129 Native American adolescents aged 14-19. Regression analyses with
      self-reported data indicated two major findings. Ethnic identity interacted with
      stereotype threat to predict academic achievement, where participants with high
      ethnic identity and low stereotype threat scores reported higher grade point
      averages. Ethnic identity also interacted with perceived discrimination to
      predict hopelessness, where participants with low ethnic identity and high
      perceived discrimination scores were higher in hopelessness. Findings are
      discussed in light of the joint role that ethnic identity and perceived bias have
      in relationship to developmental outcomes in Native American adolescents.

PMID- 28453209
TI  - Growth Mixture Modeling of Adolescent Body Mass Index Development: Longitudinal
      Patterns of Internalizing Symptoms and Physical Activity.
AB  - Growth mixture modeling was used to identify different trajectories of body mass
      index (BMI) among adolescents ages 10-15 from a national sample. Three distinct
      classes were found for both boys and girls: "normative" (90.9% and 89.7%), "high
      increasing" (6.3% and 7.4%), and "decreasing" (2.8% and 2.9%). Multinomial
      logistic regression identified family income as predictive of class membership
      for boys and pubertal status and being rural as predictive for girls. Parent
      reported health was a common predictor across gender. Growth curves of
      internalizing symptoms and physical activity were modeled to explore trends
      across classes. Findings highlight complexities in the relations between BMI,
      internalizing symptoms, and physical activity in this developmental period.

PMID- 28453210
TI  - Letting Oneself Go Isn't Enough: Cognitively Oriented Expressive Writing Reduces
      Preadolescent Peer Problems.
AB  - Peer problems are a stressor for many early adolescents, and simple cost
      effective tools for managing peer stress are needed. Expressive writing (EW) may
      be one such tool. With a sample of middle school children aged 12-14 years (n =
      119; 53% males), this research evaluates whether cognitively oriented expressive
      writing (CEW), which focuses more on psychological self-distancing, improves
      personal well-being better than traditional EW, which focuses more on emotional
      disclosure. CEW-compared with EW-slightly enhanced long-term social adjustment
      for the entire sample, and increased positive affect for those early adolescents
      that reported more peer problems at baseline. These findings suggest that
      structured writing instructions with early adolescents may be key to
      improvements.

PMID- 28453211
TI  - Why Trust Matters: How Confidence in Leaders Transforms What Adolescents Gain
      From Youth Programs.
AB  - Youth's trust in program leaders is considered a key to the positive impact of
      youth programs. We sought to understand how trust influences youth's program
      experiences from their perspective. We interviewed 108 ethnically diverse youth
      (ages 12-19) participating in 13 arts, leadership, and technology programs.
      Analysis of these accounts suggested five ways in which youth's trust in leaders
      amplified program benefits. Trust increased youth's (1) confidence in leaders'
      guidance in program activities, (2) motivation in the program, (3) use of leaders
      for mentoring, (4) use of leaders as a model of a well-functioning relationship,
      and (5) experience of program cohesiveness. Across benefits, trust allowed youth
      to draw on leaders' expertise, opened them to new experiences, and helped
      increase youth's agency.

PMID- 28453212
TI  - Peer Group Patterns of Alcohol-Using Behaviors Among Early Adolescents in
      Victoria, Australia, and Washington State, United States.
AB  - The goal of this study was to examine and cross-nationally compare the peer group
      patterns of alcohol-drinking behaviors among cohorts of early adolescents (ages
      11-14 years) in Victoria, Australia, and Washington State, United States. Latent
      transition analysis revealed that after 1 year, transitions congruent with peer
      influence (whereby non-drinking adolescents initiated alcohol use in the presence
      of drinking peers) and reverse peer influence were observed in both states;
      however, transitions congruent with peer selection (whereby drinking adolescents
      self-selected into drinking peer groups) were only observed among Victorian early
      adolescents. Findings were interpreted to suggest that Australian family and
      cultural norms that more commonly allow early adolescent alcohol use lead to a
      higher rate of peer selection.

PMID- 28453213
TI  - Predicting Well-Being and Internalizing Symptoms in Late Adolescence From
      Trajectories of Externalizing Behavior Starting in Infancy.
AB  - This study aimed to examine the long-term prediction of well-being and
      internalizing symptoms from trajectories of externalizing behavior problems in
      921 children from a population-based sample. We found that a high stable
      trajectory of externalizing behavior from infancy (age 1.5) to mid-adolescence
      (age 14.5) predicted lower scores on life satisfaction and flourishing for both
      girls and boys (age 18.5). The high stable trajectory also predicted higher
      levels of depressive symptoms in boys and anxiety symptoms in girls (age 18.5).
      The findings are noteworthy as they document how a person-oriented study of
      externalizing behavior problems starting in infancy can predict well-being and
      internalizing in late adolescence. The findings underline the importance of early
      health promotion and problem intervention efforts.

PMID- 28453214
TI  - Developmental Outcomes of School Attachment Among Students of Mexican Origin.
AB  - We used a longitudinal community study of 674 grade school children (Grades 5, 6,
      7, and 8; 337 males, 337 females) of Mexican origin to examine outcomes of school
      attachment. Attachment to school is important in this population given the high
      level of school dropout rates of Mexican-origin students. Results indicated that,
      on average, school attachment from fifth to sixth grade remains stable, but
      declines from sixth to eighth grade. Boys had lower levels of school attachment
      at fifth grade but followed similar patterns of change as girls did. Attachment
      to teachers, peer competence, school aspirations and expectations, and substance
      use cognitions emerged as longitudinal outcomes of level or changes in school
      attachment. Gender moderated associations of school attachment.

PMID- 28453215
TI  - The Roles of Racial Discrimination, Cultural Mistrust, and Gender in Latina/o
      Youth's School Attitudes and Academic Achievement.
AB  - Gender gaps in achievement are particularly pronounced among Latina/os, who are
      among the population most affected by the academic achievement gap. This study
      examined the roles of racial discrimination, cultural mistrust, and economic
      value of education in the academic achievement of urban, low-income Latina/o
      adolescents. Participants were 346 high school students. Structural equation
      modeling revealed that the model of associations was a better fit for male
      students than for female students. Cultural mistrust mediated the relationship
      between racial discrimination and values of education, and perceived limitations
      of education predicted lower attendance rates for male students but not for
      female students. Implications for future research and interventions are
      discussed.

PMID- 28453216
TI  - The Art of Restraint: How Experienced Program Leaders Use Their Authority to
      Support Youth Agency.
AB  - The staff of youth development programs perform a delicate balancing act between
      supporting youth agency and exercising necessary authority. To understand this
      balancing in daily practice, we interviewed 25 experienced (M = 14 years) leaders
      of arts, leadership, and technology programs for high-school-aged youth. We
      obtained accounts of when, how, and why they gave advice, set limits, and
      "supported youth when disagreeing." Qualitative analysis found surprising
      similarities across leaders. They used authority to give advice and set limits,
      but did so with reasoned restraint. Maximizing youth's opportunities to learn
      from experience was central in their decision making. They described employing
      authority in intentional ways aimed at helping youth's work succeed,
      strengthening youth's agency, and building skills for agency (e.g., critical
      thinking, "clarifying intent").

PMID- 28453217
TI  - Neighborhood Qualification of the Association Between Parenting and Problem
      Behavior Trajectories Among Mexican-Origin Father-Adolescent Dyads.
AB  - To address the combined importance of fathers and neighborhoods for adolescent
      adjustment, we examined whether associations between fathers' parenting and
      adolescents' problem behaviors were qualified by neighborhood adversity. We
      captured both mainstream (e.g., authoritative) and alternative (e.g., no
      nonsense, reduced involvement) parenting styles and examined parenting and
      neighborhood effects on changes over time in problem behaviors among a sample of
      Mexican-origin father-adolescent dyads (N = 462). Compared to their counterparts
      in low-adversity neighborhoods, adolescents in high-adversity neighborhoods
      experienced greater initial benefits from authoritative fathering, greater long
      term benefits from no-nonsense fathering, and fewer costs associated with reduced
      involvement fathering. The combined influences of alternative paternal parenting
      styles and neighborhood adversity may set ethnic and racial minority adolescents
      on different developmental pathways to competence.

PMID- 28453218
TI  - Mexican American Adolescents' Emotional Support to the Family in Response to
      Parental Stress.
AB  - In this two-wave longitudinal, daily diary study that followed up with 421
      Mexican American parent-adolescent dyads (adolescents: Mage = 15 years, 50%
      males) after 1 year, we investigated the contingency between parental stressors
      and adolescents' emotional support to family members. Adolescents provided
      support to their parents and other family members at similar rates, but
      adolescents were more likely to provide support to other family members than to
      their parents on days when parents experienced a family stressor. This pattern
      was especially pronounced in families with parents who reported physical symptoms
      and adolescents with a strong sense of family obligation. Adolescents' provision
      of emotional support was associated with same-day feelings of role fulfillment,
      but not to their concurrent or long-term psychological distress.

PMID- 28453219
TI  - Clinical methods of cryopreservation for donor lymphocyte infusions vary in their
      ability to preserve functional T-cell subpopulations.
AB  - BACKGROUND: Cryopreserved donor lymphocyte infusion (DLI) products are
      manufactured and administered to treat relapse after allogeneic hematopoietic
      stem cell transplantation. Reported clinical responses to DLIs vary broadly, even
      within the same group of patients. While there is an implicit recognition of the
      fact that different manufacturing protocols may have specific effects on
      different cell types, cryopreservation protocols are frequently derived from our
      experience in the cryopreservation of stem cell products and do not account for
      the heterogeneous functional nature of DLI T-cell populations. Here, we report
      the results of a prospective, multicenter trial on the effect of four different
      cryopreservation solutions that were used to freeze DLIs compared to control DLIs
      that were refrigerated overnight. STUDY DESIGN AND METHODS: Cryopreserved
      postthawed and refrigerated specimens were analyzed side by side for their T-cell
      subpopulation content and viability, as well as T-cell proliferation, cytokine
      secretion, and cytotoxic activities. RESULTS: This study indicates that
      "homemade" 10% dimethyl sulfoxide (DMSO) results in reduced viability of
      different CD4+ T-cell populations, including T-helper, T-cytotoxic, and T
      regulatory populations, and a decrease in their proliferative and cytotoxic
      response to immunologically relevant stimuli, while the use of solutions
      containing 5% DMSO with intracellular-like cryoprotectant stabilizers maintains T
      cell function at levels similar to refrigerated control samples. CONCLUSION: This
      study has important implications in determining the best cryoprotectant solution
      for specific clinical applications in allogeneic immunotherapy.

PMID- 28453220
TI  - Teaching mands for information using 'when' to children with autism.
AB  - Previous research has evaluated contrived motivating operations to teach mands
      for information. However, literature evaluating acquisition of the mand when? is
      comparatively limited. As an extension of Shillingsburg, Bowen, Valentino, &
      Pierce (2014), we taught three children with autism to engage in mands for
      information using when under alternating conditions in which a contrived
      establishing operation was present (EOP) or absent (EOA). Following training with
      a constant prompt delay, all participants acquired the mand for information and
      demonstrated correct use of the provided information and a decrease in
      inappropriate attempts to access restricted items.

PMID- 28453221
TI  - Peri-implant bone density around implants of different lengths: A 3-year follow
      up of a randomized clinical trial.
AB  - OBJECTIVES: Short dental implants are frequently placed, however, little is known
      about the effect of the loading force regarding an enhanced crown-to-implant
      ratio. The aim of this study was therefore to assess bone density changes after a
      3-year period, on radiographs acquired from a randomized, controlled two-centre
      clinical study comparing implants of 6 and 10 mm of length. MATERIALS AND
      METHODS: Three predefined areas were chosen on standardized X-rays in order to
      assess grey-scale values of the peri-implant bone: One at the tip of the apex and
      two at half-length on the mesial and distal sides of the implant. Radiographs at
      all follow-up appointments had previously been calibrated using control fields in
      areas of constant density. RESULTS: Around short implants, peri-implant bone
      displayed significantly higher differences in grey-scale values (p = .031) after
      3 years, indicating a higher degree of mineralization. This phenomenon was not
      observed around long implants. CONCLUSIONS: A higher degree of mineralization
      around short implants was recorded. Whether this finding goes along with hampered
      bone adaptability, and accordingly, higher failure rates of short implants must
      be studied further in long-term clinical trials.

PMID- 28453222
TI  - Noncontingent reinforcement competes with response performance.
AB  - Noncontingent reinforcement is a commonly used procedure to decrease levels of
      problem behavior. Goals of this intervention are to decrease motivation,
      responding, and the functional relation between behavior and consequences, but it
      could also possibly compete with performance of alternative desirable responses.
      In the current study, we assessed the effects of noncontingent reinforcement
      arranged from 0% to 100% of sessions on performance of alternative responding
      across two experiments. Experiment 1 assessed manding (i.e., requests) maintained
      by attention and tangibles with a child with developmental disabilities and
      Experiment 2 assessed keypecking maintained by food with six pigeons. We extended
      previous research by (a) showing that noncontingent reinforcement competes with
      both the acquisition and maintenance (performance) of an alternative response,
      (b) extending the generality of the findings across nonhuman and human
      participants, and (c) eliminating influence of sequence effects through random
      manipulations of noncontingent value in pigeons. Overall, greater amounts of
      noncontingent reinforcement competed with both acquisition and maintenance of
      alternative responding.

PMID- 28453223
TI  - Molecularly imprinted polymers for the selective extraction of tiliroside from
      the flowers of Edgeworthia gardneri (wall.) Meisn.
AB  - Nano-sized molecularly imprinted polymers for tiliroside were successfully
      prepared by a precipitation polymerization method. Acrylamide, ethylene glycol
      dimethacrylate, azobisisobutyronitrile, and acetonitrile/dimethyl sulfoxide were
      used as functional monomer, cross-linker, initiator, and porogen, respectively.
      The structural features and morphological characterization of tiliroside
      imprinted polymers were characterized by Fourier transform infrared spectroscopy
      and scanning electron microscopy, respectively. The adsorption experiments
      indicated that the tiliroside-imprinted polymers exhibited high selective
      recognition property to tiliroside. Scatchard analysis indicated that the
      homogeneous-binding sites were formed in the polymers. The selectivity test
      revealed that the adsorption capacity and selectivity of polymers to tiliroside
      was significantly higher than that of rutin, astragalin, and kaempferol. Finally,
      the tiliroside-imprinted polymers were employed as adsorbents in solid-phase
      extraction for the extraction of tiliroside from the ethyl acetate extract of the
      flowers of Edgeworthia gardneri (wall.) Meisn. The results demonstrated that the
      extraction recoveries of tiliroside ranged from 69.3 to 73.5% by using tiliroside
      imprinted polymers coupled with solid-phase extraction method. These results
      indicated that the tiliroside-based molecularly imprinted solid-phase extraction
      method was proven to be an effective technique for the separation and enrichment
      of tiliroside from natural medicines.

PMID- 28453224
TI  - A reappraisal of the mechanisms underlying the cardiac complications of sickle
      cell anemia.
AB  - Anemia, hemolysis-driven vasculopathy, and intrinsic myocardial injury have been
      proposed as predisposing factors to cardiac disease in sickle cell anemia (SCA).
      The individual impact of these mechanisms on the cardiac features of SCA and the
      way they influence complications such as sudden death and dysrhythmias have been
      unclear. Recent findings of an acquired restrictive SCA-related cardiomyopathy,
      driven by myocardial fibrosis, may explain some of these cardiac features. Given
      the complexity of cardiac pathology in SCA, using additional parameters to
      tricuspid regurgitant jet velocity (left atrial volume, diastolic parameters, NT
      proBNP) may improve the accuracy of noninvasive screening for cardiopulmonary
      complications in SCA.

PMID- 28453225
TI  - Oral infection with Porphyromonas gingivalis induces peri-implantitis in a murine
      model: Evaluation of bone loss and the local inflammatory response.
AB  - AIM: Peri-implantitis is a major health concern, with unclear pathogenesis, and
      with no accessible animal models. Our aim was to establish a mouse model for peri
      implantitis and to investigate mediators of inflammation. MATERIALS AND METHODS:
      Mice were divided into implanted versus non-implanted groups. Implants were
      inserted immediately following the extraction of the upper first molar. Four
      weeks following implantation, implanted and non-implanted mice were challenged
      with either Porphyromonas gingivalis or vehicle (eight mice in each subgroup, 32
      mice in total). Alveolar bone loss and expression of inflammatory mediators in
      the soft tissue were assessed 42 days following infection. RESULTS: Porphyromonas
      gingivalis infection induced greater bone loss around implants than around teeth.
      In non-infected animals, the presence of the implant correlated with elevated
      expression of Il-10, Foxp3 and Rankl/Opg ratio, while Tnf-alpha levels were
      decreased relative to tissue around teeth. Six weeks following infection, Tnf
      alpha increased significantly while the expression of Foxp3 decreased in the
      tissue around the implants. No significant differences in anti- or pro
      inflammatory mediators were found around teeth of infected, relative to non
      infected mice. CONCLUSIONS: Oral infection with P. gingivalis of mice with
      implants induced bone loss and a shift in gingival cytokine expression. This
      mouse model enables exploration of the pathogenesis of peri-implantitis and
      testing of novel treatments.

PMID- 28453227
TI  - Anti-Inflammatory Effects of Nonprofessional Phagocyte.

PMID- 28453228
TI  - Erratum.

PMID- 28453229
TI  - A Death-and Donation-of One's Own.

PMID- 28453226
TI  - Palbociclib induces activation of AMPK and inhibits hepatocellular carcinoma in a
      CDK4/6-independent manner.
AB  - Palbociclib, a CDK4/6 inhibitor, has recently been approved for hormone receptor
      positive breast cancer patients. The effects of palbociclib as a treatment for
      other malignancies, including hepatocellular carcinoma (HCC), are of great
      clinical interest and are under active investigation. Here, we report the effects
      and a novel mechanism of action of palbociclib in HCC. We found that palbociclib
      induced both autophagy and apoptosis in HCC cells through a mechanism involving
      5' AMP-activated protein kinase (AMPK) activation and protein phosphatase 5 (PP5)
      inhibition. Blockade of AMPK signals or ectopic expression of PP5 counteracted
      the effect of palbociclib, confirming the involvement of the PP5/AMPK axis in
      palbociclib-mediated HCC cell death. However, CDK4/6 inhibition by lentivirus
      mediated shRNA expression did not reproduce the effect of palbociclib-treated
      cells, suggesting that the anti-HCC effect of palbociclib is independent of
      CDK4/6. Moreover, two other CDK4/6 inhibitors (ribociclib and abemaciclib) had
      minimal effects on HCC cell viability and the PP5/AMPK axis. Palbociclib also
      demonstrated significant tumor-suppressive activity in a HCC xenograft model,
      which was associated with upregulation of pAMPK and PP5 inhibition. Finally, we
      analyzed 153 HCC clinical samples and found that PP5 expression was highly tumor
      specific and was associated with poor clinical features. Taken together, we
      conclude that palbociclib exerted antitumor activity against HCC through the
      PP5/AMPK axis independent of CDK4/6. Our findings provide a novel mechanistic
      basis for palbociclib and reveal the therapeutic potential of targeting PP5/AMPK
      signaling with a PP5 inhibitor for the treatment of hepatocellular carcinoma.

PMID- 28453230
TI  - Confusion and Seizures in a Stem Cell Transplant Recipient.

PMID- 28453231
TI  - Tuberculosis Among Foreign-Born Persons Diagnosed >=10 Years After Arrival in the
      United States, 2010-2015.

PMID- 28453232
TI  - Repair of large saddle defects of the mandibular ridge using dual growth factor
      release-An experimental pilot study in minipigs.
AB  - AIM: To test the hypothesis that the addition of small amounts of rhVEGF to
      rhBMP2 in a polymer carrier can accomplish equivalent repair effect as a reduced
      dosage of rhBMP2 compared to rhBMP2 alone. MATERIALS AND METHODS: Defects were
      created bilaterally in the mandibles of 18 minipigs. In 12 test animals, defects
      were filled with 0.5 g particulate PDLLA/CaCO3 composite loaded with 400 MUg
      rhBMP2/50 MUg rhVEGF165 on one side and 800 MUg rhBMP2 on the other. After 4 and
      13 weeks, the animals were evaluated each for area of new bone formation (mm2)
      and bone density (area %). RESULTS: Area of newly formed bone was higher in
      defects with carriers loaded with 400 MUg rhBMP2 50 ug VEGF165 than in defects
      with 800 MUg rhBMP2 after 4 weeks (11.97 versus 7.97 mm2; p = 0.043) and 13 weeks
      (72.48 versus 62.2 mm2; p = .028). Defects filled with blank carrier exhibited
      less bone after 13 weeks (42.75 mm2; p = .039 and .020 respectively).
      CONCLUSIONS: Delivery of rhBMP2 from a polymer carrier can improve repair of
      large saddle defects of the mandibular ridge. Addition of small amounts of rhVEGF
      can increase bone formation and at the same time reduce the dosage of rhBMP2.

PMID- 28453233
TI  - Proteomic analysis of oral cancer reveals new potential therapeutic targets
      involved in the Warburg effect.
AB  - Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) has
      been reported to disrupt tumour metabolism and to promote anticancer activity
      through interfering with the Warburg effect. This study is to investigate whether
      Warburg effect-related proteins also could be identified in oral tumour lesions
      and to explore the functional significance of PPARalpha in metabolic shift. Five
      pairs of tongue tumour tissues and adjacent reference tissues obtained from 4
      NQO/arecoline induced mouse model were analyzed by 2-d-gel-electrophoresis and LC
      MS. Further, the hexokinase II level, pyruvate dehydrogenase (PDH) activity, and
      metabolites of glycolysis and TCA cycle were all examined in order to validate
      the effect of PPARalpha on metabolic shift. Changes in protein expression levels
      revealed that seven proteins, which were involved in glycolysis, the
      tricarboxylic acid cycle, and the respiratory chain, were down-regulated in
      tumour tissues. We found that activation of PPARalpha through fenofibrate could
      inhibit oral cancer cell growth and switch the way of energy production from the
      Warburg effect to oxidative phosphorylation. Fenofibrate induced a reduction of
      hexokinase II protein levels, increases in PDH activity and metabolites of the
      TCA cycle, and an impairment of ATP production. These findings suggested that
      activation of the PPARalpha to reprogram the metabolic pathway might impair the
      Warburg effect and trigger cancer cell death. The study provides a novel view of
      changes in protein expression profiles involved in the Warburg effect during oral
      tumourigenesis. Activation of the PPARalpha to impair the Warburg effect might
      offer a new strategy for oral cancer treatment.

PMID- 28453234
TI  - The effects of 100 dB 1-kHz and 22-kHz tones as punishers on lever pressing in
      rats.
AB  - Aversive control is an important yet understudied process of learning. One reason
      aversive control may be relatively understudied is ethical concerns about painful
      stimuli (e.g., electric shock). High decibel broad-band noise and 22-kHz
      vocalizations both demonstrably affect rodent behavior while not necessarily
      being painful. The goal of this study was to determine if 100-dB 22-kHz-pure
      tones were differentially more effective in reducing operant response rates in
      rats. We examined whether 22-kHz pure tones would function as aversive stimuli,
      specifically as positive punishers. The effects of response-dependent as well as
      continuously presented 22-kHz and 1-kHz tones on rate of response maintained by
      variable interval 30-s food deliveries were assessed across several conditions.
      We found that response rates were lower when tones were presented response
      dependently than when tones were presented continuously throughout a session. We
      also found that the lower response rates obtained with response-dependent 22-kHz
      tones were not significantly different from response rates obtained with response
      dependent 1-kHz tones. The primary conclusion of this experiment is that both 1
      kHz and 22-kHz tones functioned as punishers, but that the 22-kHz tones were not
      differentially more effective in reducing response rate.

PMID- 28453236
TI  - Mood Versus Memory.

PMID- 28453235
TI  - Endothelial cells activate the cancer stem cell-associated NANOGP8 pathway in
      colorectal cancer cells in a paracrine fashion.
AB  - In colorectal cancer (CRC), cancer stem cells (CSCs) have been hypothesized to
      mediate cell survival and chemoresistance. Previous studies from our laboratory
      described a role for liver parenchymal endothelial cells (LPECs) in mediating the
      CSC phenotype in CRC cells in a paracrine/angiocrine fashion. The objectives of
      this study were to determine whether endothelial cells (ECs) from different
      organs can induce the CSC phenotype in CRC cells and to elucidate the signaling
      pathways involved. We treated a newly developed CRC cell line (HCP-1) and
      established CRC cell lines (HT29 and SW480) with conditioned medium (CM) from
      primary ECs isolated from nonmalignant liver, lung, colon mucosa, and kidney. Our
      results showed that CM from ECs from all organs increased the number of CSCs, as
      determined by sphere formation, and protein levels of NANOG and OCT4 in CRC
      cells. With the focus of further elucidating the role of the liver vascular
      network in mediating the CSC phenotype, we demonstrated that CM from LPECs
      increased resistance to 5-fluorouracil in CRC cells. Moreover, we showed that
      LPEC CM specifically induced NANOGP8 expression in CRC cells by specific enzyme
      digestion and a luciferase reporter assay using a vector containing the NANOGP8
      promoter. Lastly, we found that LPEC CM-induced NANOGP8 expression and sphere
      formation were mediated by AKT activation. Our studies demonstrated a paracrine
      role for ECs in regulating the CSC phenotype and chemoresistance in CRC cells by
      AKT-mediated induction of NANOGP8. These studies suggest a more specific approach
      to target CSCs by blocking the expression of NANOGP8 in cancer cells.

PMID- 28453237
TI  - A Case of Persistent Delirium Resolved Promptly With Suvorexant.

PMID- 28453238
TI  - Attentiveness of Dermatologists in the Middle East to Psychocutaneous Medicine.
AB  - Objective: Patients with skin diseases often have psychological problems and
      complications that require assessment and treatment. The main objective of this
      study was to explore attentiveness of dermatologists to psychiatric symptoms in
      their patients. Methods: A previously validated online questionnaire was used to
      explore the attitude and experience of dermatologists practicing in the Middle
      East toward the assessment of the psychiatric needs of their patients. The survey
      also inquired about awareness of available resources in dealing with
      psychodermatology. This online survey was conducted between October 2011 and
      October 2012. Results: Of 70 invited dermatologists, 57 (81%) completed the
      survey. Fifteen respondents (31%) received no training and had attended no
      educational events on psychodermatology. Only 19 respondents (33%) were able to
      identify psychodermatology as psychiatric components of skin diseases and
      dermatologic symptoms of psychiatric disorders. Twenty respondents (41%) reported
      frequent experience with psychodermatology, and 14 (28%) were "very comfortable"
      in diagnosing and treating psychodermatology patients. Twenty-two respondents
      (47%) recognized psychocutaneous involvement in 10% to 25% of their patients,
      while 18 (36%) recognized it in < 10% of their patients. Recognized diagnoses
      that required referral for psychiatric assessment included trichotillomania
      (34%), delusion of parasitosis (22%), depression (18%), dysmorphophobias (16%),
      dermatitis (10%), and venereophobia (10%). Forty-five respondents (90%) were
      unaware of psychodermatology resources. The majority of respondents expressed
      interest in education on depression, anxiety, adjustment disorders, and body
      dysmorphic disorder. Conclusions: Psychocutaneous involvements are common among
      dermatologic patients. A large number of the surveyed dermatologists had no
      training or education in psychodermatology. A lack of familiarity with patient
      and family resources on psychocutaneous conditions was also evident. These
      findings support the need for improvement in training and education in
      psychodermatology.

PMID- 28453239
TI  - Screening Physical or Sexual Abuse Victims for Substance Abuse.

PMID- 28453240
TI  - Virological response and resistances over 12 months among HIV-infected children
      less than two years receiving first-line lopinavir/ritonavir-based antiretroviral
      therapy in Cote d'Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort.
AB  - INTRODUCTION: Lopinavir/ritonavir-based antiretroviral therapy (ART) is
      recommended for all HIV-infected children less than three years. However, little
      is known about its field implementation and effectiveness in West Africa. We
      assessed the 12-month response to lopinavir/ritonavir-based antiretroviral
      therapy in a cohort of West African children treated before the age of two years.
      METHODS: HIV-1-infected, ART-naive except for a prevention of mother-to-child
      transmission (PMTCT), tuberculosis-free, and less than two years of age children
      with parent's consent were enrolled in a 12-month prospective therapeutic cohort
      with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and
      Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500
      copies/mL) and its correlates were assessed. RESULTS: Between May 2011 and
      January 2013, 156 children initiated ART at a median age of 13.9 months
      (interquartile range: 7.8-18.4); 63% were from Abidjan; 53% were girls; 37% were
      not exposed to any PMTCT intervention or maternal ART; mother was the main
      caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4.
      After 12 months on ART, 11 children had died (7%), 5 were lost-to-follow
      up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of
      those followed-up. When adjusting for country and gender, the access to tap water
      at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval
      (CI): 1.09-6.94), the mother as the main caregiver versus the father (aOR: 2.82,
      95% CI: 1.03-7.71), and the increase of CD4 percentage greater than 10% between
      inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05-6.18) were
      significantly associated with a higher rate of VS. At 12 months, 28 out of 29
      children with VL >=1000 copies/mL had a resistance genotype test: 21 (75%) had
      >=1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4%
      to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART
      initiation. CONCLUSION: Twelve-month VS rate on lopinavir/ritonavir-based ART was
      high, comparable to those in Africa or high-income countries. The father as the
      main child caregiver and lack of access to tap water are risk factors for viral
      failure and justify a special caution to improve adherence in these easy-to
      identify situations before ART initiation. Public health challenges remain to
      optimize outcomes in children with earlier ART initiation in West Africa.

PMID- 28453242
TI  - New HIV testing technologies in the context of a concentrated epidemic and
      evolving HIV prevention: qualitative research on HIV self-testing among men who
      have sex with men and transgender women in Yangon, Myanmar.
AB  - INTRODUCTION: Global effort to increase early diagnosis and engagement in HIV
      care emphasize the importance of developing novel approaches to reaching those
      missed by traditional methods. Such needs are particularly great for men who have
      sex with men (MSM), transgender women (TW), and other populations who face
      stigma. Myanmar's HIV epidemic is concentrated among key populations and the
      revised National Strategy aims to reduce late diagnosis and barriers to care to
      curb HIV incidence among these groups. HIV self-testing (HIVST) may be one method
      to improve testing and diagnosis among key populations, by placing HIV testing
      and disclosure within the individual's control. METHODS: Formative, qualitative
      research including in-depth interviews with adult MSM (N = 12) and TW (N = 13)
      and focus group discussions with MSM, TW, and community key informants (N = 35)
      were conducted in June-September 2015 in Yangon, Myanmar. To inform a subsequent
      HIV care continuum intervention, including HIVST, participants' opinions and
      perceptions about HIVST were elicited. RESULTS: The confidentiality and privacy
      of HIVST, particularly as it related to disclosure of HIV status and sexual
      behaviour, was widely recognized among participants. These major advantages were
      further supported by the opportunity to avoid stigma, convenience of self-testing
      (reduced need for transportation and time to go to clinics), and the availability
      of a pain-free testing option. Participants weighed these benefits against
      perceived disadvantages of HIVST, the majority of which centred on the perception
      that HIVST does not include counselling. Participants were concerned that
      potential lack of counselling would result in poor mental health outcomes,
      inadequate linkage to HIV care and surveillance, and reductions in disclosure of
      HIV status. Participants did not view these disadvantages as an impediment, but
      provided suggestions for future implementation of HIVST in Myanmar. CONCLUSION:
      MSM and TW are optimistic about the confidentiality and privacy afforded by HIVST
      but wanted HIV counselling and linkage to appropriate services. The domestic
      reprioritization of HIV and opening of the country to international support has
      substantially increased the availability of HIV treatment and provides new
      opportunities, like HIVST, to potentially improve the HIV response for key
      populations who are at risk for HIV acquisition.

PMID- 28453241
TI  - Stigma, access to healthcare, and HIV risks among men who sell sex to men in
      Nigeria.
AB  - INTRODUCTION: Among men who have sex with men (MSM), men who sell sex (MSS) may
      be subject to increased sexual behaviour-related stigma that affects uptake of
      healthcare and risk of sexually transmitted infections (STIs). The objectives of
      this study were to characterize stigma, access to care, and prevalence of HIV
      among MSS in Nigeria. METHODS: Respondent-driven sampling was used to recruit MSM
      in Abuja and Lagos into the ongoing TRUST/RV368 study, which provides HIV testing
      and treatment. Detailed behavioural data were collected by trained interviewers.
      MSS were identified by self-report of receiving goods or money in exchange for
      sex with men. Poisson regression with robust error variance was used to explore
      the impact of sex-selling on the risk of HIV. RESULTS: From 12 initial seed
      participants, 1552 men were recruited from March 2013-March 2016. Of these, 735
      (47.4%) reported sex-selling. Compared to other MSM, MSS were younger (median 22
      vs. 24 years, p < 0.001) and more likely to identify as gay/homosexual (42.4% vs.
      31.5%, p < 0.001). MSS were more likely to report perceived and experienced
      stigmas such as healthcare avoidance (27.6% vs. 21.5%, p = 0.005) and verbal
      harassment (39.2% vs. 26.8%, p < 0.001). Total HIV prevalence was 53.4%. After
      controlling for other factors, HIV prevalence among MSS was similar to that
      observed among other MSM (relative risk 0.94 [95% confidence interval 0.84
      1.05]). CONCLUSION: These data highlight increased sexual behaviour-related
      stigma affecting MSS, as compared with other MSM, that limits uptake of
      healthcare services. The distinct characteristics and risks among MSS suggest the
      need for specific interventions to optimize linkage to HIV prevention and
      treatment services in Nigeria.

PMID- 28453244
TI  - A "Cap" on Medicaid: How Block Grants, Per Capita Caps, and Capped Allotments
      Might Fundamentally Change the Safety Net.
AB  - Changing the Medicaid program is a top priority for the Republican party. Common
      themes from GOP proposals include converting Medicaid from a jointly financed
      entitlement benefit to a form of capped federal financing. While proponents of
      this reform argue that it would provide greater flexibility and a more
      predictable budget for state governments, serious consequences would likely
      result for Medicaid enrollees and state governments. Under all three scenarios
      promoted by Republicans--block grants, capped allotments, and per capita caps
      most states would face increased costs. For all three scenarios, the capped
      nature of the funding guarantees that the real value of funds would decrease in
      future years relative to what would be expected from growth under the current
      program. Although the federal government would undoubtedly realize savings from
      all three scenarios, the impact might lead states to reduce benefits and
      services, create waiting lists, impose cost-sharing on a traditionally low-income
      enrollee population, or impose other obstacles to coverage. Nationally, as many
      as 20.5 million Americans stand to lose coverage under the proposed Medicaid
      changes. In California, up to 6 million people could lose coverage if changes to
      the Medicaid program were coupled with the repeal of coverage for the expansion
      population.

PMID- 28453245
TI  - External Magnetic Field-Enhanced Chemo-Photothermal Combination Tumor Therapy via
      Iron Oxide Nanoparticles.
AB  - The development of multifunctional nanoplatforms based on magnetic nanoparticles
      (MNPs) has attracted increasing attention. MNPs especially exhibit excellent
      responsiveness under the guidance of an external magnetic field (MF), resulting
      in tumor-specific, targeted delivery. The behavior and magnetic-targeting
      efficiency of MNPs largely depend on their physiochemical properties, especially
      the particle size; however, the optimal size range may vary across the multiple
      bioapplications associated with multifunctional nanoparticles. The optimal size
      range of nanoparticles for external MF-mediated targeted delivery has rarely been
      reported. In this work, we synthesized a series of monodisperse Fe3O4
      nanoparticles with identical surface properties ranging in size from 10 to 310
      nm, and we systematically investigated their behavior and MF-assisted antitumor
      efficacy. Our data indicated that smaller Fe3O4 nanoparticles exhibited greater
      cellular internalization, while larger Fe3O4 nanoparticles showed greater tumor
      accumulation. Larger Fe3O4 nanoparticles exhibited stronger magnetic
      responsiveness both in vitro and in vivo, which could be used to further induce
      increased accumulation of nanoparticles and their payload (e.g., doxorubicin)
      into the tumor site under the guidance of an external MF. Our work demonstrated
      that larger Fe3O4 nanoparticles, with a diameter of up to 310 nm, exhibited the
      best magnetic-targeting efficiency mediated by an external MF and the strongest
      antitumor efficacy from combination photothermal-chemotherapy. Our results could
      serve as a valuable reference for the future design of MNPs and their targeted
      delivery via the modulation of an external MF.

PMID- 28453243
TI  - Factors associated with retention in Option B+ in Malawi: a case control study.
AB  - INTRODUCTION: There are limited data on factors associated with retention in
      Option B+. We sought to explore the characteristics of women retained in Option
      B+ in Malawi, with a focus on the role of HIV disclosure, awareness of partner
      HIV status, and knowledge around the importance of Option B+ for maternal-child
      health. Methods We performed a case-control study of HIV-infected women in Malawi
      initiated on antiretroviral therapy (ART) under Option B+. Cases were enrolled if
      they met criteria for default from Option B+ (out of ART for >60 days), and
      controls were enrolled in approximately 3:1 ratio if they were retained in care
      for at least 12 months. We surveyed socio-demographic characteristics, HIV
      disclosure and awareness of partner HIV status, self-report about receiving pre
      ART education, and knowledge of Option B+. Univariate logistic regression was
      performed to determine factors associated with retention. Multivariate logistic
      regression model was used to evaluate the relationship between HIV disclosure,
      Option B+ knowledge, and retention after adjusting for age, schooling, and travel
      time to clinic. RESULTS: We enrolled 50 cases and 153 controls. Median age was 30
      years (interquartile range (IQR) 25-34), and the majority (82%) initiated ART
      during pregnancy at a median gestational age of 24 weeks (IQR 16-28). Ninety-one
      per cent of the cases (39/43) who started ART during pregnancy defaulted by three
      months postpartum. HIV disclosure to the primary sex partner was more common
      among women retained in care (100% versus 78%, p < 0.001). Odds of retention were
      significantly higher among women with: age >25 years (odds ratio (OR) 2.44),
      completion of primary school (OR 3.06), awareness of partner HIV status (OR
      5.20), pre-ART education (OR 6.17), higher number of correct answers to Option B+
      knowledge questions (OR 1.82), and support while taking ART (OR 3.65). Pre-ART
      education and knowledge were significantly correlated (r = 0.43, p < 0.001). In
      multivariate analysis, awareness of partner HIV status (OR 4.07, 95% confidence
      interval (CI) 1.51-10.94, p = 0.02) and Option B+ knowledge (OR 1.60, 95% CI 1.15
      2.23, p = 0.004) remained associated with retention. CONCLUSIONS: Interventions
      that address partner disclosure and strengthen pre-ART education around the
      benefits of ART for maternal and child health should be evaluated to improve
      retention in Malawi's Option B+ programme.

PMID- 28453246
TI  - Robust and Flexible Aramid Nanofiber/Graphene Layer-by-Layer Electrodes.
AB  - Aramid nanofibers (ANFs), or nanoscale Kevlar fibers, are of interest for their
      high mechanical performance and functional nanostructure. The dispersible nature
      of ANFs opens up processing opportunities for creating mechanically robust and
      flexible nanocomposites, particularly for energy and power applications. The
      challenge is to manipulate ANFs into an electrode structure that balances
      mechanical and electrochemical performance to yield a robust and flexible
      electrode. Here, ANFs and graphene oxide (GO) sheets are blended using layer-by
      layer (LbL) assembly to achieve mechanically flexible supercapacitor electrodes.
      After reduction, the resulting electrodes exhibit an ANF-rich structure where
      ANFs act as a polymer matrix that interfacially interacts with reduced graphene
      oxide sheets. It is shown that ANF/GO deposition proceeds by hydrogen bonding and
      pi-pi interactions, leading to linear growth (1.2 nm/layer pairs) and a
      composition of 75 wt % ANFs and 25 wt % GO sheets. Chemical reduction leads to a
      high areal capacitance of 221 MUF/cm2, corresponding to 78 F/cm3. Nanomechanical
      testing shows that the electrodes have a modulus intermediate between those of
      the two native materials. No cracks or defects are observed upon flexing ANF/GO
      films 1000 times at a radius of 5 mm, whereas a GO control shows extensive
      cracking. These results demonstrate that electrodes containing ANFs and reduced
      GO sheets are promising for flexible, mechanically robust energy and power.

PMID- 28453247
TI  - Building an Electronic Bridge via Ag Decoration To Enhance Kinetics of Iron
      Fluoride Cathode in Lithium-Ion Batteries.
AB  - As a typical multielectron cathode material for lithium-ion batteries, iron
      fluoride (FeF3) and its analogues suffer from poor electronic conductivity and
      low actual specific capacity. Herein, we introduce Ag nanoparticles by silver
      mirror reaction into the FeF3.0.33H2O cathode to build the electronic bridge
      between the solid (active materials) and liquid (electrolyte) interface. The
      crystal structures of as-prepared samples are characterized by X-ray diffraction
      and Rietveld refinement. Moreover, the density of states of FeF3.0.33H2O and
      FeF3.0.33H2O/Ag (Ag-decorated FeF3.0.33H2O) samples are calculated using the
      first principle density functional theory. The FeF3.0.33H2O/Ag cathodes exhibit
      significant enhancements on the electrochemical performance in terms of the cycle
      performance and rate capability, especially for the Ag-decorated amount of 5%. It
      achieves an initial capacity of 168.2 mA h g-1 and retains a discharge capacity
      of 128.4 mA h g-1 after 50 cycles in the voltage range of 2.0-4.5 V. It
      demonstrates that Ag decoration can reduce the band gap, improve electronic
      conductivity, and elevate intercalation/deintercalation kinetics.

PMID- 28453248
TI  - Heterocyclic Aromatics in Petroleum Coke, Snow, Lake Sediments, and Air Samples
      from the Athabasca Oil Sands Region.
AB  - The aromatic fractions of snow, lake sediment, and air samples collected during
      2011-2014 in the Athabasca oil sands region were analyzed using two-dimensional
      gas chromatography following a nontargeted approach. Commonly monitored aromatics
      (parent and alkylated-polycyclic aromatic hydrocarbons and dibenzothiophenes)
      were excluded from the analysis, focusing mainly on other heterocyclic aromatics.
      The unknowns detected were classified into isomeric groups and tentatively
      identified using mass spectral libraries. Relative concentrations of heterocyclic
      aromatics were estimated and were found to decrease with distance from a
      reference site near the center of the developments and with increasing depth of
      sediments. The same heterocyclic aromatics identified in snow, lake sediments,
      and air were observed in extracts of delayed petroleum coke, with similar
      distributions. This suggests that petroleum coke particles are a potential source
      of heterocyclic aromatics to the local environment, but other oil sands sources
      must also be considered. Although the signals of these heterocyclic aromatics
      diminished with distance, some were detected at large distances (>100 km) in snow
      and surface lake sediments, suggesting that the impact of industry can extend >50
      km. The list of heterocyclic aromatics and the mass spectral library generated in
      this study can be used for future source apportionment studies.

PMID- 28453249
TI  - Complete Mapping of Complex Disulfide Patterns with Closely-Spaced Cysteines by
      In-Source Reduction and Data-Dependent Mass Spectrometry.
AB  - Mapping of disulfide bonds is an essential part of protein characterization to
      ensure correct cysteine pairings. For this, mass spectrometry (MS) is the most
      widely used technique due to fast and accurate characterization. However, MS
      based disulfide mapping is challenged when multiple disulfide bonds are present
      in complicated patterns. This includes the presence of disulfide bonds in nested
      patterns and closely spaced cysteines. Unambiguous mapping of such disulfide
      bonds typically requires advanced MS approaches. In this study, we exploited in
      source reduction (ISR) of disulfide bonds during the electrospray ionization
      process to facilitate disulfide bond assignments. We successfully developed a LC
      ISR-MS/MS methodology to use as an online and fully automated partial reduction
      procedure. Postcolumn partial reduction by ISR provided fast and easy
      identification of peptides involved in disulfide bonding from nonreduced
      proteolytic digests, due to the concurrent detection of disulfide-containing
      peptide species and their composing free peptides. Most importantly, intermediate
      partially reduced species containing only a single disulfide bond were also
      generated, from which unambiguous assignment of individual disulfide bonds could
      be done in species containing closely spaced disulfide bonds. The strength of
      this methodology was demonstrated by complete mapping of all four disulfide bonds
      in lysozyme and all 17 disulfide bonds in human serum albumin, including nested
      disulfide bonds and motifs of adjacent cysteine residues.

PMID- 28453250
TI  - Correction to "A Smorgasbord of Carbon: Electrochemical Analysis of Cobalt
      Bis(benzenedithiolate) Complex Adsorption and Electrocatalytic Activity on
      Diverse Graphitic Supports".

PMID- 28453251
TI  - Influence of Manure Application on the Environmental Resistome under Finnish
      Agricultural Practice with Restricted Antibiotic Use.
AB  - The co-occurrence of antibiotic-resistance genes (ARGs) and mobile genetic
      elements (MGEs) in farm environments can potentially foster the development of
      antibiotic-resistant pathogens. We studied the resistome of Finnish dairy and
      swine farms where use of antibiotics is limited to treating bacterial infections
      and manure is only applied from April to September. The resistome of manure,
      soil, and tile drainage water from the ditch was investigated from the beginning
      of the growing season until forage harvest. The relative ARG and MGE abundance
      was measured using a qPCR array with 363 primer pairs. Manure samples had the
      highest abundance of ARGs and MGEs, which increased during storage. Immediately
      following land application, the ARGs abundant in manure were detected in soil,
      but their abundance decreased over time with many becoming undetectable. This
      suggests that increases in ARG abundances after fertilizing are temporary and
      occur annually under agricultural practices that restrict antibiotic use. A few
      of the ARGs were detected in the ditch water, but most of them were undetected in
      the manure. Our results document the dissipation and dissemination off farm of
      ARGs under Finnish limited antibiotic use and suggest that such practices could
      help reduce the load of antibiotic-resistance genes in the environment.

PMID- 28453252
TI  - Polymer Inclusion Membranes with Condensed Phase Membrane Introduction Mass
      Spectrometry (CP-MIMS): Improved Analytical Response Time and Sensitivity.
AB  - Condensed phase membrane introduction mass spectrometry (CP-MIMS) is an online,
      in situ analysis technique for low volatility analytes. Analytes diffuse through
      a hollow fiber membrane, where they are then dissolved by a liquid (condensed)
      acceptor phase flowing through the membrane lumen. Permeating analytes are
      entrained to an atmospheric pressure ionization source for subsequent measurement
      by a mass spectrometer. Larger analytes, with inherently lower diffusivities,
      suffer from lengthy response times and lower sensitivity, limiting the use of CP
      MIMS for their online, real-time measurement. We present the use of a heptane
      cosolvent in a methanol acceptor phase in combination with a polydimethylsiloxane
      (PDMS) membrane. The heptane generates an in situ polymer inclusion membrane
      (PIM) with the PDMS. We report improved measurement response times and greater
      sensitivity across a suite of analytes studied (gemfibrozil, nonylphenol,
      triclosan, 2,4,6-trichlorophenol, and naphthenic acids), with detection limits in
      the low parts per trillion (ppt) range. These improvements are attributed to
      increasing analyte diffusivities, as well as increased analyte partitioning
      across the PIM. Response times are ~3* faster for the larger analytes studied,
      and calibration sensitivity is improved by up to ~3.5* using 0.046 mole fraction
      heptane in the methanol acceptor. We report the use of short sample exposure
      times and the use of non-steady-state signals to reduce the analytical duty
      cycle, and illustrate that the use of a PIM provides a simple and robust variant
      of CP-MIMS amenable to rapid screening of analytes in complex samples.

PMID- 28453253
TI  - Athabasca Oil Sands Petcoke Extract Elicits Biochemical and Transcriptomic
      Effects in Avian Hepatocytes.
AB  - Petroleum coke or "petcoke" is a granular carbonaceous material produced during
      the upgrading of heavy crude oils, including bitumen. Petcoke dust was recently
      reported as an environmental contaminant in the Athabasca oil sands region, but
      the ecotoxicological hazards posed by this complex bitumen-derived material
      including those to avian species-have not been characterized. In this study,
      solvent extracts (x) of delayed and fluid petcoke (xDP and xFP) were prepared and
      dissolved in dimethyl sulfoxide. A water-accommodated fraction of delayed petcoke
      (waDP) was also prepared. Graded concentrations of xDP, xFP, and waDP were
      administered to chicken and double-crested cormorant hepatocytes to determine
      effects on 7-ethoxyresorufin-O-deethylase (EROD) activity, porphyrin
      accumulation, and mRNA expression. Polycyclic aromatic compounds (PACs) were
      characterized, and xDP, xFP, and waDP had total PAC concentrations of 93 000,
      270, and 5.3 ng/mL. The rank order of biochemical and transcriptomic responses
      was xDP > xFP > waDP (e.g., EROD EC50s were lower for xDP compared to xFP and
      waDP). A total of 22, 18, and 4 genes were altered following exposure to the
      highest concentrations of xDP, xFP, and waDP, respectively, using a chicken PCR
      array comprising 27 AhR-related genes. To provide more exhaustive coverage of
      potential toxicity pathways being impacted, two avian ToxChip PCR arrays-chicken
      and double-crested cormorant-were utilized, and xDP altered the expression of
      more genes than xFP. Traditional PAC-related toxicity pathways and novel
      mechanisms of action were identified in two avian species following petcoke
      extract exposure. Extrapolation to real-world exposure scenarios must consider
      the bioavailability of the extracted PACs compared to those in exposed organisms.

PMID- 28453254
TI  - Gene Transfection Mediated by Catiomers Requires Free Highly Charged Polymer
      Chains To Overcome Intracellular Barriers.
AB  - The prospective use of the block copolymers poly(ethylene oxide)113-b-poly[2
      (diethylamino)ethyl methacrylate]50 (PEO113-b-PDEA50) and poly[oligo(ethylene
      glycol)methyl ether methacrylate]70-b-poly[oligo(ethylene glycol)methyl ether
      methacrylate10-co-2-(diethylamino)ethyl methacrylate47-co-2
      (diisopropylamino)ethyl methacrylate47] (POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47))
      as nonviral gene vectors was evaluated. The polymers are able to properly
      condense DNA into nanosized particles (RH ~ 75 nm), which are marginally
      cytotoxic and can be uptaken by cells. However, the green fluorescent protein
      (GFP) expression assays evidenced that DNA delivery is essentially negligible
      meaning that intracellular trafficking hampers efficient gene release.
      Subsequently, we demonstrate that cellular uptake and particularly the quantity
      of GFP-positive cells are substantially enhanced when the block copolymer
      polyplexes are produced and further supplemented by BPEI chains (branched
      polyethylenimine). The dynamic light scattering/electrophoretic light
      scattering/isothermal titration calorimetry data suggest that such a strategy
      allows the adsorption of BPEI onto the surface of the polyplexes, and this
      phenomenon is responsible for increasing the size and surface charge of the
      assemblies. Nevertheless, most of the BPEI chains remain freely diffusing in the
      systems. The biological assays confirmed that cellular uptake is enhanced in the
      presence of BPEI and principally, the free highly charged polymer chains play the
      central role in intracellular trafficking and gene transfection. These
      investigations pointed out that the transfection efficiency versus cytotoxicity
      issue can be balanced by a mixture of BPEI and less cytotoxic agents such as for
      instance the proposed block copolymers.

PMID- 28453255
TI  - Characterization and Identification of Dityrosine Cross-Linked Peptides Using
      Tandem Mass Spectrometry.
AB  - The use of mass spectrometry coupled with chemical cross-linking of proteins has
      become a powerful tool for proteins structure and interactions studies. Unlike
      structural analysis of proteins using chemical reagents specific for lysine or
      cysteine residues, identification of gas-phase fragmentation patterns of
      endogenous dityrosine cross-linked peptides have not been investigated.
      Dityrosine cross-linking in proteins and peptides are clinical markers of
      oxidative stress, aging, and neurodegenerative diseases including Alzheimer's
      disease and Parkinson's disease. In this study, we investigated and characterized
      the fragmentation pattern of a synthetically prepared dityrosine cross-linked
      dimer of Abeta(1-16) using ESI tandem mass spectrometry. We then detailed the
      fragmentation pattern of dityrosine cross-linked Abeta(1-16), using collision
      induced dissociation (CID), higher-energy collision induced dissociation (HCD),
      electron transfer dissociation (ETD), and electron capture dissociation (ECD).
      Application of these generic fragmentation rules of dityrosine cross-linked
      peptides allowed for the identification of dityrosine cross-links in peptides of
      Abeta and alpha-synuclein generated in vitro by enzymatic peroxidation. We
      report, for the first time, the dityrosine cross-linked residues in human
      hemoglobin and alpha-synuclein under oxidative conditions. Together these tools
      open up the potential for automated analysis of this naturally occurring post
      translation modification in neurodegenerative diseases as well as other
      pathological conditions.

PMID- 28453256
TI  - Intraperitoneal Administration of Neural Stem Cell-Nanoparticle Conjugates
      Targets Chemotherapy to Ovarian Tumors.
AB  - Ovarian cancer is particularly aggressive once it has metastasized to the
      abdominal cavity (stage III). Intraperitoneal (IP) as compared to intravenous
      (IV) administration of chemotherapy improves survival for stage III ovarian
      cancer, demonstrating that concentrating chemotherapy at tumor sites has
      therapeutic benefit; unfortunately, IP therapy also increases toxic side effects,
      thus preventing its completion in many patients. The ability to target
      chemotherapy selectively to ovarian tumors while sparing normal tissue would
      improve efficacy and decrease toxicities. We have previously shown that tumor
      tropic neural stem cells (NSCs) dramatically improve the intratumoral
      distribution of nanoparticles (NPs) when given intracerebrally near an orthotopic
      brain tumor or into a flank xenograft tumor. Here, we show that NPs either
      conjugated to the surface of NSCs or loaded within the cells are selectively
      delivered to and distributed within ovarian tumors in the abdominal cavity
      following IP injection, with no evidence of localization to normal tissue. IP
      administration is significantly more effective than IV administration, and NPs
      carried by NSCs show substantially deeper penetration into tumors than free NPs.
      The NSCs and NPs target and localize to ovarian tumors within 1 h of
      administration. Pt-loaded silica NPs (SiNP[Pt]) were developed that can be
      transported in NSCs, and it was found that the NSC delivery of SiNP[Pt] (NSC
      SiNP[Pt]) results in higher levels of Pt in tumors as compared to free drug or
      SiNP[Pt]. To the best of our knowledge, this work represents the first
      demonstration that cells given IP can target the delivery of drug-loaded NPs.

PMID- 28453257
TI  - One Filter, One Sample, and the N- and O-Glyco(proteo)me: Toward a System to
      Study Disorders of Protein Glycosylation.
AB  - A method has been developed for release/isolation of O-glycans from glycoproteins
      in whole cell lysates for mass spectrometric analysis. Cells are lysed in SDS,
      which is then exchanged for urea and ammonium bicarbonate in a centrifugal
      filter, before treating with NH4OH to release O-glycans. Following
      centrifugation, O-glycans are recovered in the filtrate. Sonication achieves O
      glycan release in 1 h. Combining the established protocol for filter-aided N
      glycan separation, here optimized for enhanced PNGase F efficiency, with the
      developed O-glycan release method allows analysis of both N- and O-glycans from
      one sample, in the same filter unit, from 0.5 to 1 million cells. The method is
      compatible with subsequent analysis of the residual protein by liquid
      chromatography-mass spectrometry (LC-MS) after glycan release. The medium
      throughput approach is amenable to analysis of biological replicates, offering a
      simple way to assess the often subtle changes to glycan profiles accompanying
      differentiation and disease progression, in a statistically robust way.

PMID- 28453258
TI  - Study of Lithium Silicide Nanoparticles as Anode Materials for Advanced Lithium
      Ion Batteries.
AB  - The development of high-performance silicon anodes for the next generation of
      lithium ion batteries (LIBs) evokes increasing interest in studying its lithiated
      counterpart-lithium silicide (LixSi). In this paper we report a systematic study
      of three thermodynamically stable phases of LixSi (x = 4.4, 3.75, and 2.33) plus
      nitride-protected Li4.4Si, which are synthesized via the high-energy ball-milling
      technique. All three LixSi phases show improved performance over that of
      unmodified Si, where Li4.4Si demonstrates optimum performance with a discharging
      capacity of 3306 (mA h)/g initially and maintains above 2100 (mA h)/g for over 30
      cycles and above 1200 (mA h)/g for over 60 cycles at the current density of 358
      mA/g of Si. A fundamental question studied is whether different electrochemical
      paradigms, that is, delithiation first or lithiation first, influence the
      electrode performance. No significant difference in electrode performance is
      observed. When a nitride layer (LixNySiz) is created on the surface of Li4.4Si,
      the cyclability is improved to retain the capacity above 1200 (mA h)/g for more
      than 80 cycles. By increasing the nitridation extent, the capacity retention is
      improved significantly from the average decrease of 1.06% per cycle to 0.15% per
      cycle, while the initial discharge capacity decreases due to the inactivity of Si
      in the LixNySiz layer. Moreover, the Coulombic efficiencies of all LixSi-based
      electrodes in the first cycle are significantly higher than that of a Si
      electrode (~90% vs 40-70%).

PMID- 28453259
TI  - Direct In Situ Mass Specific Absorption Spectra of Biomass Burning Particles
      Generated from Smoldering Hard and Softwoods.
AB  - Particles from smoldering biomass burning (BB) represent a major source of
      carbonaceous aerosol in the terrestrial atmosphere. In this study, mass specific
      absorption spectra of laboratory-generated smoldering wood particles (SWP) from 3
      hardwood and 3 softwood species were measured in situ. Absorption data spanning
      from lambda = 500 to 840 nm were collected using a photoacoustic spectrometer
      coupled to a supercontinuum laser with a tunable wavelength and bandwidth filter.
      SWP were size- (electrical mobility) and mass-selected prior to optical
      characterization allowing data to be reported as mass-specific absorption cross
      sections (MAC). The median measured MAC at lambda = 660 nm for smoldering oak
      particles was 1.1 (0.57/1.8) * 10-2 m2 g-1 spanning from 83 femtograms (fg) to
      517 fg (500 nm <= mobility diameter <=950 nm), MAC values in parentheses are the
      16th and 84th percentiles of the measured data (i.e., 1sigma). The collection of
      all six wood species (Oak, Hickory, Mesquite, Western redcedar, Baldcypress, and
      Blue spruce) had median MAC values ranging from 1.4 * 10-2 m2 g-1 to 7.9 * 10-2
      m2 g-1 at lambda = 550 nm with absorption Angstrom exponents (AAE) between 3.5
      and 6.2. Oak, Western redcedar, and Blue spruce possessed statistically similar
      (p > 0.05) spectra while the spectra of Hickory, Mesquite, and Baldcypress were
      distinct (p < 0.01) as calculated from a point-by-point analysis using the Wilcox
      rank-sum test.

PMID- 28453260
TI  - Origin of Outstanding Phase and Moisture Stability in a Na3P1-xAsxS4 Superionic
      Conductor.
AB  - Sodium ion (Na) solid-state electrolytes (SSEs) are critical to address notorious
      safety issues associated with liquid electrolytes used in the current Na ion
      batteries. Fulfilling multiple innovations is a grand challenge but is imperative
      for advanced Na ion SSEs, such as a combination of high ionic conductivity and
      excellent chemical stability. Here, our first-principles and phonon calculations
      reveal that Na3P1-xAsxS4 (0 <= x <= 1) is a solid-state superionic conductor
      stabilized at 0 K by zero-point vibrational energy and at finite temperatures by
      vibrational and configurational entropies. Especially, our integrated first
      principles and experimental approach indicates that Na3P1-xAsxS4 is dry-air
      stable. Additionally, the alloying element arsenic greatly enhances the moisture
      (i.e., H2O) stability of Na3P1-xAsxS4 by shifting the reaction products from the
      easy-forming oxysulfides (such as Na3POS3 and Na3PO2S2 with H2S release) to the
      difficult-forming hydrates (such as Na3P1-xAsxS4.nH2O with n = 8 and/or 9) due
      mainly to a weaker As-O affinity compared to that of P-O. The present work
      demonstrates that alloying is able to achieve multiple innovations for solid
      state electrolytes, such as a desirable superionic conductor with not only a high
      ionic conductivity (for example, 1.46 mS/cm at room temperature achieved in
      Na3P0.62As0.38S4) but also an excellent chemical stability with respect to
      temperature, composition, and moisture.

PMID- 28453262
TI  - Periodic Trends in Olefin Epoxidation over Group IV and V Framework-Substituted
      Zeolite Catalysts: A Kinetic and Spectroscopic Study.
AB  - Group IV and V framework-substituted zeolites have been used for olefin
      epoxidation reactions for decades, yet the underlying properties that determine
      the selectivities and turnover rates of these catalysts have not yet been
      elucidated. Here, a combination of kinetic, thermodynamic, and in situ
      spectroscopic measurements show that when group IV (i.e., Ti, Zr, and Hf) or V
      (i.e., Nb and Ta) transition metals are substituted into zeolite *BEA, the metals
      that form stronger Lewis acids give greater selectivities and rates for the
      desired epoxidation pathway and present smaller enthalpic barriers for both
      epoxidation and H2O2 decomposition reactions. In situ UV-vis spectroscopy shows
      that these group IV and V materials activate H2O2 to form pools of hydroperoxide,
      peroxide, and superoxide intermediates. Time-resolved UV-vis measurements and the
      isomeric distributions of Z-stilbene epoxidation products demonstrate that the
      active species for epoxidations on group IV and V transition metals are only M
      OOH/-(O2)2- and M-(O2)- species, respectively. Mechanistic interpretations of
      kinetic data suggest that these group IV and V materials catalyze cyclohexene
      epoxidation and H2O2 decomposition through largely identical Eley-Rideal
      mechanisms that involve the irreversible activation of coordinated H2O2 followed
      by reaction with an olefin or H2O2. Epoxidation rates and selectivities vary over
      five- and two-orders of magnitude, respectively, among these catalysts and depend
      exponentially on the energy for ligand-to-metal charge transfer (LMCT) and the
      functional Lewis acid strength of the metal centers. Together, these observations
      show that more electrophilic active-oxygen species (i.e., lower-energy LMCT) are
      more reactive and selective for epoxidations of electron-rich olefins and explain
      why Ti-based catalysts have been identified as the most active among early
      transition metals for these reactions. Further, H2O2 decomposition (the
      undesirable reaction pathway) possesses a weaker dependence on Lewis acidity than
      epoxidation, which suggests that the design of catalysts with increased Lewis
      acid strength will simultaneously increase the reactivity and selectivity of
      olefin epoxidation.

PMID- 28453263
TI  - Strategy for the Realization of Efficient Solution-Processable Phosphorescent
      Organic Light-Emitting Devices: Design and Synthesis of Bipolar
      Alkynylplatinum(II) Complexes.
AB  - A new class of highly luminescent bipolar alkynylplatinum(II) complexes has been
      synthesized, characterized, and applied as phosphorescent dopants in the
      fabrication of solution-processable organic light-emitting devices (OLEDs).
      Through the incorporation of a delicate balance of electron-donating carbazole
      moieties and electron-accepting phenylbenzimidazole or oxadiazole moieties into
      the platinum(II) core, the platinum(II) complexes have been demonstrated to
      exhibit bipolar charge transport character with high photoluminescence quantum
      yields of up to 0.75 in thin films. The introduction of meta-linkages into the
      complexes further helps weaken the donor-acceptor interactions, facilitating
      better carrier-transporting abilities. More importantly, high-performance
      solution-processable green-emitting OLEDs with maximum current efficiencies of up
      to 57.4 cd A-1 and external quantum efficiencies of up to 16.0% have been
      realized. This is among the best performances for solution-processable
      phosphorescent OLEDs reported based on platinum(II) complexes as well as bipolar
      metal complexes.

PMID- 28453261
TI  - Comparison of Metabolomics Approaches for Evaluating the Variability of Complex
      Botanical Preparations: Green Tea (Camellia sinensis) as a Case Study.
AB  - A challenge that must be addressed when conducting studies with complex natural
      products is how to evaluate their complexity and variability. Traditional methods
      of quantifying a single or a small range of metabolites may not capture the full
      chemical complexity of multiple samples. Different metabolomics approaches were
      evaluated to discern how they facilitated comparison of the chemical composition
      of commercial green tea [Camellia sinensis (L.) Kuntze] products, with the goal
      of capturing the variability of commercially used products and selecting
      representative products for in vitro or clinical evaluation. Three metabolomic
      related methods-untargeted ultraperformance liquid chromatography-mass
      spectrometry (UPLC-MS), targeted UPLC-MS, and untargeted, quantitative 1HNMR-were
      employed to characterize 34 commercially available green tea samples. Of these
      methods, untargeted UPLC-MS was most effective at discriminating between green
      tea, green tea supplement, and non-green-tea products. A method using reproduced
      correlation coefficients calculated from principal component analysis models was
      developed to quantitatively compare differences among samples. The obtained
      results demonstrated the utility of metabolomics employing UPLC-MS data for
      evaluating similarities and differences between complex botanical products.

PMID- 28453264
TI  - Polymorphous Al-MOFs Based on V-Shaped Linker Molecules: Synthesis, Properties,
      and in Situ Investigation of Their Crystallization.
AB  - The in situ and systematic high-throughput investigation of the system Al3+/4,4'
      benzophenonedicarboxylic acid (H2BPDC)/DMF/H2O in the presence of various
      additives was carried out, and a new Al-MOF of composition [Al(OH)(BPDC)],
      denoted as CAU-21-BPDC, was obtained. Its crystal structure was determined from
      single-crystal X-ray diffraction data (space group I422, a = b = 17.2528(7) A, c
      = 23.864(1) A). The structure is built up by octanuclear rings of cis corner
      sharing AlO6 polyhedra forming the inorganic building unit (IBU). These {Al8O8}
      IBUs are arranged in a bcu packing and connected via BPDC2- ions in a way that
      each IBU is linked via two linker molecules to each of the eight adjacent IBUs.
      Thus, accessible, one-dimensional modulated pores with a diameter between 3.6 and
      6.5 A are formed. In addition, tetrahedral cavities are formed by the BPDC2-
      linker molecules. The framework of CAU-21-BPDC is polymorphous with that of CAU-8
      BPDC, which contains one-dimensional chains of trans corner-sharing AlO6
      polyhedra connected by BPDC2- ions. Replacing H2BPDC by 4,4'-oxydibenzoic acid
      (H2ODB), which contains an oxygen atom between the phenyl rings instead of a keto
      group, leads to the synthesis of Al-MOFs isoreticular with CAU-8-BPDC and CAU-21
      BPDC. In addition, a coordination polymer, [Al(HODB)2(OH)], was discovered and
      structurally characterized. The structure of CAU-8-ODB was refined from powder X
      ray diffraction data, while a Pawley refinement was carried out for CAU-21-ODB to
      determine the lattice parameters and confirm phase purity. The structure of CAU
      21-ODB was confirmed using density functional theory (DFT) calculations. A
      thorough characterization shows that the CAU-8 and CAU-21-type structures are
      stable up to 350 and 300  degrees C in air, respectively, almost independent of
      the linker molecules incorporated. The former MOFs are porous toward N2 and CO2,
      while the latter only adsorb CO2.

PMID- 28453265
TI  - Yunnaneic Acid B, a Component of Pulmonaria officinalis Extract, Prevents
      Peroxynitrite-Induced Oxidative Stress in Vitro.
AB  - Our work reveals that the aerial parts of Pulmonaria officinalis L. are a new
      source of yunnaneic acid B. We studied antioxidant activity and cytotoxicity of
      this compound (1-50 MUg/mL) and its contents in various plant extracts. This is
      the first study confirming the presence of yunnaneic acid B in P. officinalis L.
      and Pulmonaria obscura Dumort and hence in the Boraginaceae family. Determination
      of 1,1-diphenyl-2-picrylhydrazyl radical reduction and peroxynitrite-scavenging
      efficacy in inorganic experimental systems provided EC50 values of 7.14 and 50.45
      MUg/mL, respectively. Then we examined the antioxidant action of yunnaneic acid B
      in blood plasma under peroxynitrite-induced oxidative stress in vitro. Yunnaneic
      acid B effectively diminished oxidative damage to blood plasma proteins and
      lipids. Furthermore, it was able to prevent the peroxynitrite-induced decrease in
      nonenzymatic antioxidant capacity of blood plasma. Additionally, cytotoxicity of
      yunnaneic acid B (at concentrations <=50 MUg/mL) toward peripheral blood
      mononuclear cells was excluded.

PMID- 28453266
TI  - Metabolomics Approach to Investigate Estrogen Receptor-Dependent and Independent
      Effects of o,p'-DDT in the Uterus and Brain of Immature Mice.
AB  - Previous studies have demonstrated the endocrine disruption of o,p'-DDT. In this
      study, we used a 1H NMR based metabolomics approach to investigate the estrogenic
      effects of o,p'-DDT (300 mg/kg) on the uterus and brain after 3 days of oral
      gavage administration, and ethynylestradiol (EE, 100 MUg/kg) was used as a
      positive control. A supervised statistical analysis (PLS-DA) indicated that o,p'
      DDT exerted both estrogenic receptor-(ER)-dependent and independent effects on
      the uterus but mainly ER-independent effects on the brain at metabolome levels,
      which was verified by coexposing with the antiestrogenic ICI 182,780. Four
      changed metabolites-glycine, choline, fumarate, and phenylalanine-were identified
      as ER-independent alterations in the uterus, while more metabolites, including
      gamma-aminobutyrate, N-acetyl aspartate, and some amino acids, were disturbed
      based on the ER-independent mechanism in the brain. Together with biological end
      points, metabolomics is a promising approach to study potential estrogenic
      chemicals.

PMID- 28453267
TI  - Visible-Light-Driven Photocatalytic CO2 Reduction by a Ni(II) Complex Bearing a
      Bioinspired Tetradentate Ligand for Selective CO Production.
AB  - A Ni(II) complex bearing an S2N2-type tetradentate ligand inspired by the active
      site of carbon monoxide dehydrogenase was found to selectively catalyze CO2
      reduction to produce CO in a photocatalytic system using [Ru(bpy)3]2+ (bpy = 2,2'
      bipyridine) as a photosensitizer and 1,3-dimethyl-2-phenyl-2,3-dihydro-1H
      benzo[d]imidazole (BIH) as an electron donor. The Ni(II) complex shows a high
      turnover number over 700 with high CO selectivity of >99% and quantum yield of
      1.42% in the photocatalytic system.

PMID- 28453269
TI  - Production of Protein Concentrate and 1,3-Propanediol by Wheat-Based Thin
      Stillage Fermentation.
AB  - Fermentation of wheat with yeast produces thin stillage (W-TS) and distiller's
      wet grains. A subsequent fermentation of W-TS (two-stage fermentation, TSF) with
      endemic bacteria at 25 and 37  degrees C decreased glycerol and lactic acid
      concentrations, while 1,3-propanediol (1,3-PD) and acetic acid accumulated with
      greater 1,3-PD and acetic acid produced at 37  degrees C. During TSF, W-TS
      colloids coagulated and floated in the fermentation medium producing separable
      liquid and slurry fractions. The predominant endemic bacteria in W-TS were
      Lactobacillus panis, L. gallinarum, and L. helveticus, and this makeup did not
      change substantially as fermentation progressed. As nutrients were exhausted,
      floating particles precipitated. Protein contents of slurry and clarified liquid
      increased and decreased, respectively, as TSF progressed. The liquid was easily
      filtered through an ultrafiltration membrane. These results suggested that TSF is
      a novel method for W-TS clarification and production of protein concentrates and
      1,3-PD from W-TS.

PMID- 28453268
TI  - Ir-Catalyzed ortho-Borylation of Phenols Directed by Substrate-Ligand
      Electrostatic Interactions: A Combined Experimental/in Silico Strategy for
      Optimizing Weak Interactions.
AB  - A strategy for affecting ortho versus meta/para selectivity in Ir-catalyzed C-H
      borylations (CHBs) of phenols is described. From selectivity observations with
      ArylOBpin (pin = pinacolate), it is hypothesized that an electrostatic
      interaction between the partial negatively charged OBpin group and the partial
      positively charged bipyridine ligand of the catalyst favors ortho selectivity.
      Experimental and computational studies designed to test this hypothesis support
      it. From further computational work a second generation, in silico designed
      catalyst emerged, where replacing Bpin with Beg (eg = ethylene glycolate) was
      predicted to significantly improve ortho selectivity. Experimentally, reactions
      employing B2eg2 gave ortho selectivities > 99%. Adding triethylamine
      significantly improved conversions. This ligand-substrate electrostatic
      interaction provides a unique control element for selective C-H
      functionalization.

PMID- 28453270
TI  - Vitepyrroloids A-D, 2-Cyanopyrrole-Containing Labdane Diterpenoid Alkaloids from
      the Leaves of Vitex trifolia.
AB  - Vitepyrroloids A-D (1-4), four new 2-cyano-substituted pyrrole-ring-containing
      labdane diterpenoids, were isolated from the leaves of Vitex trifolia. Their
      structures were elucidated based on spectroscopic data analysis. The absolute
      configuration of compound 1 was determined by X-ray diffraction. Compounds 1-4
      are unprecedented labdane diterpenoids featuring a 2-cyano-substituted pyrrole
      ring. Compound 1 showed cytotoxic activity against a human nasopharyngeal
      carcinoma cell line (CNE1) with an IC50 value of 8.7 MUM.

PMID- 28453271
TI  - An Efficient Metadynamics-Based Protocol To Model the Binding Affinity and the
      Transition State Ensemble of G-Protein-Coupled Receptor Ligands.
AB  - A generally applicable metadynamics scheme for predicting the free energy profile
      of ligand binding to G-protein-coupled receptors (GPCRs) is described. A common
      and effective collective variable (CV) has been defined using the ideally placed
      and highly conserved Trp6.48 as a reference point for ligand-GPCR distance
      measurement and the common orientation of GPCRs in the cell membrane. Using this
      single CV together with well-tempered multiple-walker metadynamics with a funnel
      like boundary allows an efficient exploration of the entire ligand binding path
      from the extracellular medium to the orthosteric binding site, including
      vestibule and intermediate sites. The protocol can be used with X-ray structures
      or high-quality homology models (based on a high-quality template and after
      thorough refinement) for the receptor and is universally applicable to agonists,
      antagonists, and partial and reverse agonists. The root-mean-square error (RMSE)
      in predicted binding free energies for 12 diverse ligands in five receptors (a
      total of 23 data points) is surprisingly small (less than 1 kcal mol-1). The
      RMSEs for simulations that use receptor X-ray structures and homology models are
      very similar.

PMID- 28453272
TI  - Bacterial Iron Uptake Pathways: Gates for the Import of Bactericide Compounds.
AB  - Bacterial resistance to most antibiotics in clinical use has reached alarming
      proportions. A challenge for modern medicine will be to discover new antibiotics
      or strategies to combat multidrug resistant bacteria, especially Gram-negative
      bacteria for which the situation is particularly critical. Vectorization of
      bactericide compounds by siderophores (iron chelators produced by bacteria) is a
      promising strategy able to considerably increase the efficacy of drugs. Such a
      Trojan horse strategy can also extend activity of specific Gram-positive
      antibiotics to Gram-negative bacteria.

PMID- 28453273
TI  - Half-Metallicity in One-Dimensional Metal Trihydride Molecular Nanowires.
AB  - The development of one-dimensional (1D) molecular nanowires with high spin
      polarization is important for both fundamental research and practical
      applications in nanoscale spintronics. Herein, we report new 1D metal trihydride
      molecular nanowires MH3 (M = Sc, Cr, Mn, and Co) with versatile magnetic
      properties on the basis of first-principles calculations and molecular assembly
      of their molecular motifs. Among the 1D nanowires considered, CrH3, MnH3, and
      CoH3 are either antiferromagnetic or ferromagnetic in their ground states. In
      particular, CoH3 nanowire is a half-metal, which ideally could provide 100% spin
      polarized currents. Moreover, carrier doping in MnH3 nanowire can induce a
      transition from ferromagnetic metal to half-metal. Strong metal-metal interaction
      in 1D MH3 nanowires is responsible to versatile magnetic properties and high
      Curie temperature. Born-Oppenheimer molecular dynamics simulation indicates that
      these nanowires are stable at elevated temperature. In particular, the ScH3
      nanowire appears to have the highest structural stability at temperature 1200 K.
      These novel properties of 1D MH3 nanowires render their potential applications in
      nanoscale spintronics.

PMID- 28453274
TI  - A Porous Array of Clock Qubits.
AB  - Realizing atomic-level spatial control over qubits, the fundamental units of both
      quantum information processing systems and quantum sensors, constitutes a crucial
      cross-field challenge. Toward this end, embedding electronic-spin-based qubits
      within the framework of a crystalline porous material is a promising approach to
      create precise arrays of qubits. Realizing porous hosts for qubits would also
      impact the emerging field of quantum sensing, whereby porosity would enable
      analytes to infuse into a sensor matrix. However, building viable qubits into a
      porous material is an appreciable challenge because of the extreme sensitivity of
      qubits to local magnetic noise. To insulate these frameworks from ambient
      magnetic signals, we borrowed from atomic physics the idea to exploit clock
      transitions at avoided level crossings. Here, sensitivity to magnetic noise is
      inherently limited by the flat slope of the so-called clock transition. More
      specifically, we created an array of clocklike qubits within a metal-organic
      framework by combining coordination chemistry considerations with the fundamental
      concept of atomic clock transitions. Electron paramagnetic resonance studies
      verify a clocklike transition for the hosted cobalt(II) spins in the framework
      [(TCPP)Co0.07Zn0.93]3[Zr6O4(OH)4(H2O)6]2, the first demonstration in any porous
      material. The clocklike qubits display lifetimes of up to 14 MUs despite abundant
      local nuclear spins, illuminating a new path toward proof-of-concept quantum
      sensors and processors with high inherent structural precision.

PMID- 28453275
TI  - Dielectric Response of Cytoplasmic Water and Its Connection to the Vitality of
      Human Red Blood Cells. II. The Influence of Storage.
AB  - Maintaining an appropriate inventory of packaged blood products is a critical
      part of modern medicine. Consequently, the assessment of red blood cell (RBC)
      functionality is instrumental for the monitoring of the quality of stored RBC
      (sRBC) in the blood bank. We present a comprehensive study of sRBC lesion
      kinetics in SAGM (saline, adenine, glucose, mannitol) solution, using microwave
      dielectric spectroscopy (0.5-50 GHz) and cell deformability. As part of the
      research, we have isolated the microwave dielectric response of cytoplasmic water
      in sRBC. The extracted dielectric parameters are sensitive to the age of the
      cells and, in particular, to the critical moment of transition from discocyte to
      echinocyte. From the analysis of the dielectric relaxation as a function of
      storage-duration, we postulate that the behavior is rooted in the delicate
      interplay between bound and bulk water in the cellular interior. In particular,
      the microwave dielectric response reflects the moment when the continuous
      diffusion of oxygen to the cell and the oxygenation of hemoglobin affects the
      role played by water in the maintenance of cell integrity. These results open a
      possible new avenue for the noninvasive inspection of stored red blood cells,
      permitting a true inventory system for the modern blood bank.

PMID- 28453276
TI  - Computational Chemical Kinetics for the Reaction of Criegee Intermediate CH2OO
      with HNO3 and Its Catalytic Conversion to OH and HCO.
AB  - The kinetics and mechanisms for the reaction of the Criegee intermediate CH2OO
      with HNO3 and the unimolecular decomposition of its reaction product CH2(O)NO3
      are important in atmospheric chemistry. The potential-energy profile of the
      reactions predicted with the CCSD(T)/aug-cc-pVTZ//B3LYP/aug-cc-pVTZ method shows
      that the initial association yields a prereaction complex that isomerizes by H
      migration to yield excited intermediate nitrooxymethyl hydroperoxide NO3CH2OOH*
      with internal energy ~44 kcal mol-1. A fragmentation of this excited intermediate
      produces CH2(O)NO3 + OH with its transition state located 5.0 kcal mol-1 below
      that of the reactants. Further decomposition of CH2(O)NO3 produces HCO + HNO3,
      forming a catalytic cycle for destruction of CH2OO by HNO3. The rate coefficients
      and product-branching ratios were calculated in the temperature range 250-700 K
      at pressure 20-760 Torr (N2) using the variational-transition-state and Rice
      Ramsperger-Kassel-Marcus (RRKM) theories. The predicted total rate coefficient
      for reaction CH2OO + HNO3 at 295 K, 5.1 * 10-10 cm3 molecule-1 s-1, agrees
      satisfactorily with the experimental value, (5.4 +/- 1.0) * 10-10 cm3 molecule-1
      s-1. The predicted branching ratios at 295 K are 0.21 for the formation of
      NO3CH2OOH and 0.79 for CH2(O)NO3 + OH at a pressure of 40 Torr (N2), and 0.79 for
      the formation of NO3CH2OOH and 0.21 for CH2(O)NO3 + OH at 760 Torr (N2). This new
      catalytic conversion of CH2OO to HCO + OH by HNO3 might have significant impact
      on atmospheric chemistry.

PMID- 28453277
TI  - Combined Effect of the Picoloyl Protecting Group and Triflic Acid in Sialylation.
AB  - The stereoselective synthesis of sialosides is still one of the major challenges
      in carbohydrate chemistry. The synthesis and glycosidation of novel sialyl donors
      bearing a picoloyl substituent at C-4 are reported. High stereoselectivities and
      faster reactions were observed in the presence of an excess of triflic acid. The
      acid excess does not have the same effect on conventional sialyl donors, which
      suggests a possible synergistic effect of the picoloyl substituent and the
      triflic acid.

PMID- 28453278
TI  - Hydrophobization of Silica Nanoparticles in Water: Nanostructure and Response to
      Drying Stress.
AB  - We report on the impact of surface hydrophobization on the structure of aqueous
      silica dispersions and how this structure resists drying stress. Hydrophilic
      silica particles were hydrophobized directly in water using a range of
      organosilane precursors, with a precise control of the grafting density. The
      resulting nanostructure was precisely analyzed by a combination of small-angle X
      ray scattering (SAXS) and cryo-microscopy (cryo-TEM). Then, the dispersion was
      progressively concentrated by drying, and the evolution of the nanostructures as
      a function of the grafting density was followed by SAXS. At the fundamental
      level, because the hydrophobic character of the silica surfaces could be varied
      continuously through a precise control of the grafting density, we were able to
      observe how the hydrophobic interactions change particles interactions and
      aggregates structures. Practically, this opened a new route to tailor the final
      structure, the residual porosity, and the damp-proof properties of the fully
      dried silica. For example, regardless of the nature of the hydrophobic precursor,
      a grafting density of 1 grafter per nm2 optimized the interparticle interactions
      in solution in view to maximize the residual porosity in the dried material (0.9
      cm3/g) and reduced the water uptake to less than 4% in weight compared to the
      typical value of 13% for hydrophilic particles (at T = 25  degrees C and relative
      humidity = 80%).

PMID- 28453279
TI  - Monte Carlo Simulations of the Uptake of Chiral Compounds on Solid Surfaces.
AB  - A Monte Carlo algorithm was developed and used to describe and explain previous
      experimental results associated with the kinetics of the uptake of chiral
      molecules on solid surfaces. The specific system simulated in this study is the
      adsorption of propylene oxide (PO) on Pt(111) surfaces. The surface was
      represented by a square lattice, and the time evolution of the adsorption,
      starting from a clean surface, was simulated via a number of sequential events
      chosen using a stochastic approach based on the so-called Master equation and
      derived from the formalism advanced by Gillespie. Two main assumptions were
      required to explain the experimental results: (1) that adsorption is assisted by
      previously adsorbed molecules, that is, that the probability for sticking is
      higher next to other adsorbates than on empty isolated sites, and (2) that the
      geometry adopted by the new adsorbate next to an old one is defined and different
      for homochiral versus heterochiral pairs. Our model was able to quantitatively
      reproduce the experimental data and to explain a number of important observations
      associated with the fact that the adsorbates are chiral, including the following:
      (1) the final PO saturation depends on the enantiocomposition of the gas phase,
      yielding a layer approximately 20% less dense with a racemic mixture than with
      enantiopure S-PO or R-PO; (2) the same changes in saturation coverages are seen
      if PO of different chirality are dosed sequentially; (3) the sticking probability
      is also higher with enantiopure adsorbates, at least in the initial stages of the
      uptake; (4) the sticking probability initially increases with increasing
      exposure, until reaching a maximum at about 20% of saturation; and (5) the
      adsorbed layers do not show any long-range ordering but display small linear
      clusters. It was also possible to reproduce the experimental observation that the
      addition of a prochiral molecule such as propylene (Py) to a surface dosed with a
      small amount of a chiral "seed" (PO) leads to an amplification of the initial
      enantioselectivity of that surface.

PMID- 28453280
TI  - Synthesis of Functionalized Alkenes by a Transition-Metal-Free Zweifel Coupling.
AB  - The Zweifel reaction is a powerful method for the synthesis of alkenes, serving
      as a transition-metal-free alternative to the Suzuki-Miyaura reaction. To date,
      the scope of the Zweifel coupling has been rather narrow and has focused mainly
      on the coupling of vinyllithium reagents to synthesize simple aryl- and alkyl
      substituted olefins. Herein, the development of a general transition-metal-free
      coupling process enabling the coupling of Grignard reagents or organolithiums is
      described. This method enables the enantiospecific synthesis of a wide variety of
      functionalized acyclic and cyclic olefin products.

PMID- 28453281
TI  - Designing Ligands to Isolate ZnLn and Zn2Ln Complexes: Field-Induced Single-Ion
      Magnet Behavior of the ZnDy, Zn2Dy, and Zn2Er Analogues.
AB  - A new H3L Schiff base ligand with three defined compartments, namely, two
      internal NNO and one external O6, was designed to allocate metal ions of
      different size. This ligand allows isolating heterodinuclear
      [ZnLn(HL)(NO3)(OAc)(D)](NO3) (Ln = Tb, D = H2O, ZnTb; Ln = Dy, D = CH3OH, ZnDy;
      and Ln = Er, D = CH3OH, ZnEr) complexes, where one of the NNO pockets allocates a
      zinc(II) ion, while the other one is empty, or heterotrinuclear
      [Zn2Ln(L)(NO3)2(OAc)2(H2O)] (Ln = Dy, Zn2Dy and Ln = Er, Zn2Er) compounds, where
      each NNO compartment accommodates ZnII. All these compounds crystallize with
      different solvates, and their structures were unequivocally determined by single
      crystal X-ray diffraction studies. Complexes ZnDy, Zn2Dy, and Zn2Er behave as
      single-molecule magnets in the presence of an external dc field of 1000 Oe, with
      Ueff values of 41.05, 47.69, and 20.81 K, respectively, while ZnTb and ZnEr do
      not.

PMID- 28453282
TI  - Stretchable Thermoelectric Generators Metallized with Liquid Alloy.
AB  - Conventional thermoelectric generators (TEGs) are normally hard, rigid, and flat.
      However, most objects have curvy surfaces, which require soft and even
      stretchable TEGs for maximizing efficiency of thermal energy harvesting. Here,
      soft and stretchable TEGs using conventional rigid Bi2Te3 pellets metallized with
      a liquid alloy is reported. The fabrication is implemented by means of a tailored
      layer-by-layer fabrication process. The STEGs exhibit an output power density of
      40.6 MUW/cm2 at room temperature. The STEGs are operational after being
      mechanically stretched-and-released more than 1000 times, thanks to the compliant
      contact between the liquid alloy interconnects and the rigid pellets. The
      demonstrated interconnect scheme will provide a new route to the development of
      soft and stretchable energy-harvesting avenues for a variety of emerging
      electronic applications.

PMID- 28453283
TI  - Ionic Liquid-Mediated Hydrofluorination of o-Azaxylylenes Derived from 3
      Bromooxindoles.
AB  - The hydrofluorination reaction of 3-bromooxindole using mild HF reagents in an
      ionic liquid is described. This transformation can operate at room temperature to
      give a series of 3-substituted 3-fluorooxindole derivatives including racemic BMS
      204352 (MaxiPost). The mechanistic study about interactions between HF and 3
      butyl-1-methylimidazolium tetrafluoroborate [bmim][BF4] is also discussed on the
      basis of energy calculations.

PMID- 28453284
TI  - Rearrangement of an Intermediate Cyclopropyl Ketene in a RhII-Catalyzed Formal [4
      + 1]-Cycloaddition Employing Vinyl Ketenes as 1,4-Dipoles and Donor-Acceptor
      Metallocarbenes.
AB  - A RhII-catalyzed formal [4 + 1]-cycloaddition approach toward spirooxindole
      cyclopentenones is described. The diastereoselective cyclopropanation of vinyl
      ketenes with diazooxindoles as C1 synthons initiated a relatively mild formal
      [1,3]-migration of an intermediate cyclopropyl ketene to provide spirooxindoles
      in good to excellent yields (36-99%).

PMID- 28453285
TI  - Pharmacological Reprogramming of Somatic Cells for Regenerative Medicine.
AB  - Lost or damaged cells in tissues and organs can be replaced by transplanting
      therapeutically competent cells. This approach requires methods that effectively
      manipulate cellular identities and properties to generate sufficient numbers of
      desired cell types for transplantation. These cells can be generated by
      reprogramming readily available somatic cells, such as fibroblasts, into induced
      pluripotent stem cells (iPSCs), which can replicate indefinitely and give rise to
      any somatic cell type. This reprogramming can be achieved with genetic methods,
      such as forced expression of pluripotency-inducing transcription factors (TFs),
      which can be further improved, or even avoided, with pharmacological agents. We
      screened chemical libraries for such agents and identified small molecules that
      enhance TF-mediated pluripotency induction in somatic cells. We also developed
      cocktails of small molecules that can functionally replace combinations of TFs
      required to induce pluripotency in mouse and human somatic cells. Importantly, we
      devised and established a general strategy to develop effective pharmacological
      cocktails for specific cellular reprogramming processes. In the search for useful
      small molecules, we also discovered and characterized previously unknown
      mechanisms pertinent to cellular reprogramming. A more direct method to access
      scarce cells for cell transplantation is transdifferentiation, which uses
      combinations of cell-type specific TFs to reprogram fibroblasts into the target
      somatic cell types across lineage boundaries. We created an alternative strategy
      for cellular transdifferentiation that epigenetically activates somatic cells by
      pairing temporal treatment with reprogramming molecules and tissue-specific
      signaling molecules to generate cells of multiple lineages. Using this cell
      activation and signaling-directed (CASD) transdifferentiation paradigm, we
      converted fibroblasts into a variety of somatic cells found in major organs, such
      as the heart, brain, pancreas, and liver. Specifically, we induced, isolated, and
      expanded (long-term) lineage-specific progenitor cells that can give rise to a
      defined range of cell types relevant to specific tissues or organs. Transplanting
      these progenitor cells or their progeny was therapeutically beneficial in animal
      models of diseases and organ damage. Importantly, we developed chemically defined
      conditions, without any genetic factors, that convert fibroblasts into cells of
      the cardiac and neural lineages, further extending the realm of pharmacological
      reprogramming of cells. Continuously advancing technologies in pharmacological
      reprogramming of cells may benefit and advance regenerative medicine. The
      established pharmacological tools have already been applied to enhance the
      processes of cellular reprogramming and improve the quality of cells for their
      clinical applications. The rapidly increasing number of readily available
      bioactive chemical tools will fuel our efforts to reprogram cells for
      transplantation therapies.

PMID- 28453286
TI  - Sugar Beet Extract (Beta vulgaris L.) as a New Natural Emulsifier: Emulsion
      Formation.
AB  - The interfacial and emulsion-forming properties of sugar beet extract (Beta
      vulgaris L.) were examined and compared to a Quillaja extract that is widely used
      within the food industry. We investigated the influence of extract concentration
      on surface activity at oil-water and air-water interfaces and on the formation of
      oil-in-water emulsions (10% w/w, pH 7). Sugar beet extract reduced the
      interfacial tension up to 38% at the oil-water interface, and the surface tension
      up to 33% at the air-water surface. The generated emulsions were negatively
      charged (zeta ~ -46 mV) and had the smallest particle sizes (d43) of ~1.3 MUm at
      a low emulsifier-to-oil ratio of 0.75:10. Applying lower or higher extract
      concentrations increased the mean particle sizes. The smallest emulsions were
      formed at an optimum homogenization pressure of 69 MPa. Higher homogenization
      pressures led to increased particle sizes. Overall, sugar beet extract showed
      high surface activity. Furthermore, the formation of small emulsion droplets was
      successful; however, the droplets were bigger compared to those from the Quillaja
      extract. These results indicate sugar beet as an effective natural emulsifier
      that may be utilized for a variety of food and beverage applications.

PMID- 28453287
TI  - Effective Inclusion of Mechanical and Electrical Anharmonicity in Excited
      Electronic States: VPT2-TDDFT Route.
AB  - We present a reliable and cost-effective procedure for the inclusion of
      anharmonic effects in excited-state energies and spectroscopic intensities by
      means of second-order vibrational perturbation theory. This development is made
      possible thanks to a recent efficient implementation of excited-state analytic
      Hessians and properties within the time-dependent density functional theory
      framework. As illustrated in this work, by taking advantage of such algorithmic
      developments, it is possible to perform calculations of excited-state infrared
      spectra of medium-large isolated molecular systems, with anharmonicity effects
      included in both the energy and property surfaces. We also explore the use of
      this procedure for the inclusion of anharmonic effects in the simulation of
      vibronic bandshapes of electronic spectra and compare the results with previous,
      more approximate models.

PMID- 28453288
TI  - Photothermal Transport of DNA in Entropy-Landscape Plasmonic Waveguides.
AB  - The ability to handle single, free molecules in lab-on-a-chip systems is key to
      the development of advanced biotechnologies. Entropic confinement offers passive
      control of polymers in nanofluidic systems by locally asserting a molecule's
      number of available conformation states through structured landscapes.
      Separately, a range of plasmonic configurations have demonstrated active
      manipulation of nano-objects by harnessing concentrated electric fields. The
      integration of these two independent techniques promises a range of sophisticated
      and complementary functions to handle, for example, DNA, but numerous
      difficulties, in particular, conflicting requirements of channel size, have
      prevented progress. Here, we show that metallic V-groove waveguides, embedded in
      fluidic nanoslits, form entropic potentials that trap and guide DNA molecules
      over well-defined routes while simultaneously promoting photothermal transport of
      DNA through the losses of plasmonic modes. The propulsive forces, assisted by in
      coupling to propagating channel plasmon polaritons, extend along the V-grooves
      with a directed motion up to ~0.5 MUm.mW-1 away from the input beam and lambda
      DNA velocities reaching ~0.2 MUm.s-1.mW-1. The entropic trapping enables the V
      grooves to be flexibly loaded and unloaded with DNA by variation of transverse
      fluid flow, a process that is selective to biopolymers versus fixed-shape objects
      and also allows the technique to address the challenges of nanoscale interaction
      volumes. Our self-aligning, light-driven actuator provides a convenient platform
      to filter, route, and manipulate individual molecules and may be realized wholly
      by wafer-scale fabrication suitable for parallelized investigation.

PMID- 28453289
TI  - Identification of Buctopamine and Mebuctopamine, a beta2 Receptor Agonist and Its
      Metabolite, in Swine Hair and Feed Additives.
AB  - 4-[2-(t-Butylamino)-1-hydroxyethyl]phenol (buctopamine, 4), a new beta2 receptor
      agonist (beta2-agonist), was found to be an adulterant in feed additives for
      swine in Taiwan, where using beta2-agonists in food-production animals is
      prohibited. Buctopamine and its metabolite, 4-[2-(t-butylamino)-1-hydroxyethyl]-2
      methoxyphenol (mebuctopamine, 2), were detected in swine hair specimens.
      Authentic compounds 2 and 4 were synthesized with 98.6% and 97.7% purity,
      respectively, as reference standards for analysis, and both compounds were more
      hydrophilic than ractopamine and clenbuterol. In a preliminary pharmacological
      evaluation, compounds 2 and 4 exhibited moderate human beta2 receptor binding
      affinity and did not show significant affinities for the human alpha1, alpha2,
      beta1, and beta3 receptors. After addition of compounds 2-4 into the beta2
      agonist library, a multiresidue analysis of 26 beta2-agonists by using triple
      quadrupole LC/MS/MS for routine screening conducted by regulatory authorities was
      established, in which the common limits of quantification for the 26 beta2
      agonists in swine feed and hair are 10 and 25 ng/g, respectively. In addition,
      the illegal use of buctopamine (4) has been effectively prevented. The results of
      this study are also useful for controlling the illegal use of new beta2-agonists
      in food-production animals.

PMID- 28453290
TI  - Enantioselective Intermolecular Addition of Aliphatic Amines to Acyclic Dienes
      with a Pd-PHOX Catalyst.
AB  - We report a method for the catalytic, enantioselective intermolecular addition of
      aliphatic amines to acyclic 1,3-dienes. In most cases, reactions proceed
      efficiently at or below room temperature in the presence of 5 mol % of a Pd
      catalyst bearing a PHOX ligand, generating allylic amines in up to 97:3 er. The
      presence of an electron-deficient phosphine within the ligand not only leads to a
      more active catalyst but also is critical for achieving high site selectivity in
      the transformation.

PMID- 28453291
TI  - Amide-Group-Directed Protonolysis of Cyclopropane: An Approach to 2,2
      Disubstituted Pyrrolidines.
AB  - Regioselective protonolytic C-C bond cleavage of acylated aminomethyl
      cyclopropanes can be achieved using trifluoroacetic acid. The intermediate
      tertiary carbenium ion undergoes an intramolecular amination to give 2,2
      substituted pyrrolidines. The strength of the acid and the amine substituent are
      important factors to achieve high regioselectivity, suggesting intramolecular
      proton transfer from the protonated amide function. Preliminary mechanistic
      studies revealed that cyclopropane cleavage proceeds with retention of
      configuration at the carbon to which the proton is attached. This observation is
      consistent with the "edge" protonation trajectory of the C-C bond.

PMID- 28453293
TI  - Predicting a Drug's Membrane Permeability: A Computational Model Validated With
      in Vitro Permeability Assay Data.
AB  - Membrane permeability is a key property to consider during the drug design
      process, and particularly vital when dealing with small molecules that have
      intracellular targets as their efficacy highly depends on their ability to cross
      the membrane. In this work, we describe the use of umbrella sampling molecular
      dynamics (MD) computational modeling to comprehensively assess the passive
      permeability profile of a range of compounds through a lipid bilayer. The model
      was initially calibrated through in vitro validation studies employing a parallel
      artificial membrane permeability assay (PAMPA). The model was subsequently
      evaluated for its quantitative prediction of permeability profiles for a series
      of custom synthesized and closely related compounds. The results exhibited
      substantially improved agreement with the PAMPA data, relative to alternative
      existing methods. Our work introduces a computational model that underwent
      progressive molding and fine-tuning as a result of its synergistic collaboration
      with numerous in vitro PAMPA permeability assays. The presented computational
      model introduces itself as a useful, predictive tool for permeability prediction.

PMID- 28453294
TI  - Photoinduced Vitamin B12-Catalysis for Deprotection of (Allyloxy)arenes.
AB  - Vitamin B12 is a natural cobalt complex that, while reduced to the
      "supernucleophilic" Co(I) form, can easily react with electrophiles via an SN2
      mechanism. It is also shown to react via an SN2' mechanism with allylic compounds
      allowing for photochemical deprotection of (allyloxy)arenes. A sustainable
      alternative to commonly used noble metal-catalyzed deprotection reactions is
      presented.

PMID- 28453295
TI  - Postinjury Exercise and Platelet-Rich Plasma Therapies Improve Skeletal Muscle
      Healing in Rats But Are Not Synergistic When Combined.
AB  - BACKGROUND: Skeletal muscle injuries are the most common sports-related injury
      and a major concern in sports medicine. The effect of platelet-rich plasma (PRP)
      injections on muscle healing is still poorly understood, and current data are
      inconclusive. PURPOSE: To evaluate the effects of an ultrasound-guided
      intramuscular PRP injection, administered 24 hours after injury, and/or
      posttraumatic daily exercise training for 2 weeks on skeletal muscle healing in a
      recently established rat model of skeletal muscle injury that highly mimics the
      muscle trauma seen in human athletes. STUDY DESIGN: Controlled laboratory study.
      METHODS: A total of 40 rats were assigned to 5 groups. Injured rats (medial
      gastrocnemius injury) received a single PRP injection (PRP group), daily exercise
      training (Exer group), or a combination of a single PRP injection and daily
      exercise training (PRP-Exer group). Untreated and intramuscular saline-injected
      animals were used as controls. Muscle force was determined 2 weeks after muscle
      injury, and muscles were harvested and evaluated by means of histological
      assessment and immunofluorescence microscopy. RESULTS: Both PRP (exhibiting 4.8
      fold higher platelet concentration than whole blood) and exercise training
      improved muscle strength (maximum tetanus force, TetF) in approximately 18%, 20%,
      and 30% of rats in the PRP, PRP-Exer, and Exer groups, respectively. Specific
      markers of muscle regeneration (developmental myosin heavy chain, dMHC) and scar
      formation (collagen I) demonstrated the beneficial effect of the tested therapies
      in accelerating the muscle healing process in rats. PRP and exercise treatments
      stimulated the growth of newly formed regenerating muscle fibers (1.5-, 2-, and
      2.5-fold increase in myofiber cross-sectional area in PRP, PRP-Exer, and Exer
      groups, respectively) and reduced scar formation in injured skeletal muscle (20%,
      34%, and 41% of reduction in PRP, PRP-Exer, and Exer groups, respectively).
      Exercise-treated muscles (PRP-Exer and Exer groups) had significantly reduced
      percentage of dMHC-positive regenerating fibers (35% and 47% decrease in dMHC
      expression, respectively), indicating that exercise therapies accelerated the
      muscle healing process witnessed by the more rapid replacement of the embryonic
      developmental myosin isoform by mature muscle myosin isoforms. CONCLUSION:
      Intramuscular PRP injection and, especially, treadmill exercise improve
      histological outcome and force recovery of the injured skeletal muscle in a rat
      injury model that imitates sports-related muscle injuries in athletes. However,
      there was not a synergistic effect when both treatments were combined, suggesting
      that PRP does not add any beneficial effect to exercise-based therapy in the
      treatment of injured skeletal muscle. CLINICAL RELEVANCE: This study demonstrates
      the efficacy of an early active rehabilitation protocol or single intramuscular
      PRP injection on muscle recovery. The data also reveal that the outcome of the
      early active rehabilitation is adversely affected by the PRP injection when the
      two therapies are combined, and this could explain why PRP therapies have failed
      in randomized clinical trials where the athletes have adhered to postinjection
      rehabilitation protocols based on the principle of early, active mobilization.

PMID- 28453296
TI  - The Zone: A Measurable (and Contagious) Exemplar of Mind-Body Integration.

PMID- 28453292
TI  - Discovery of Mixed Pharmacology Melanocortin-3 Agonists and Melanocortin-4
      Receptor Tetrapeptide Antagonist Compounds (TACOs) Based on the Sequence Ac-Xaa1
      Arg-(pI)DPhe-Xaa4-NH2.
AB  - The centrally expressed melanocortin-3 and -4 receptors (MC3R/MC4R) have been
      studied as possible targets for weight management therapies, with a preponderance
      of studies focusing on the MC4R. Herein, a novel tetrapeptide scaffold [Ac-Xaa1
      Arg-(pI)DPhe-Xaa4-NH2] is reported. The scaffold was derived from results
      obtained from a MC3R mixture-based positional scanning campaign. From these
      results, a set of 48 tetrapeptides were designed and pharmacologically
      characterized at the mouse melanocortin-1, -3, -4, and -5 receptors. This
      resulted in the serendipitous discovery of nine compounds that were MC3R agonists
      (EC50 < 1000 nM) and MC4R antagonists (5.7 < pA2 < 7.8). The three most potent
      MC3R agonists, 18 [Ac-Arg-Arg-(pI)DPhe-Tic-NH2], 1 [Ac-His-Arg-(pI)DPhe-Tic-NH2],
      and 41 [Ac-Arg-Arg-(pI)DPhe-DNal(2')-NH2] were more potent (EC50 < 73 nM) than
      the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2. This template contains a
      sequentially reversed "Arg-(pI)DPhe" motif with respect to the classical "Phe
      Arg" melanocortin signaling motif, which results in pharmacology that is first-in
      class for the central melanocortin receptors.

PMID- 28453297
TI  - Complementary and Alternative Medicine Use and Its Association with Emotional
      Status and Quality of Life in Patients with a Solid Tumor: A Cross-Sectional
      Study.
AB  - OBJECTIVES: Complementary and alternative medicine (CAM) has been used widely in
      various populations for various purposes, including emotional support and
      improvement of quality of life (QOL). However, CAM use and purposes for using CAM
      are less clear among Korean patients with a solid tumor. The purpose of this
      study was to determine the prevalence and type of CAM use, and the association
      between CAM use and anxiety, depression, and QOL in patients with a solid tumor.
      DESIGN: A cross-sectional survey. SETTING: A cancer center in Korea. SUBJECTS:
      Two hundred and sixteen patients diagnosed with a solid tumor. OUTCOME MEASURES:
      Standard questionnaires on CAM use, Hospital Anxiety and Depression Scale, and
      European Organization for Research and Treatment of Cancer QLQ-C30. RESULTS: One
      hundred thirty one patients (60.6%) reported using CAM. CAM users, compared with
      non-CAM users, were significantly younger (57.8 vs. 60.9 years, p = 0.05), had
      higher level of education (p = 0.008), had higher income (p = 0.008), were less
      likely to seek physician consultation on CAM use (p = 0.002), and had a more
      advanced stage of tumor (p = 0.003) with more distant metastasis (p = 0.001). The
      most commonly used CAM was herbal medicine (n = 89, 67.9%). CAM users had
      significantly lower anxiety (t = 5.21, p < 0.001) and depression (t = 4.90, p <
      0.001) than non-CAM users. When the effects of CAM use were tested on anxiety,
      depression, and QOL, controlling for covariates, CAM use was significantly
      associated with 8.7% and 8.8% of variance in decreasing anxiety and depression,
      but there was no unique association of CAM use with variance in QOL. CONCLUSIONS:
      CAM use is prevalent and younger age, higher education levels, higher income,
      less physician consultation, and higher cancer stage are significant correlates
      to CAM use. Controlling for covariates (e.g., gender, BMI), CAM use is
      significantly associated with lower anxiety and depression compared with those of
      non-CAM users.

PMID- 28453298
TI  - Primary ovarian insufficiency with t(5;13): a case report and literature review
      on disrupted genes.
AB  - OBJECTIVES: To report a woman with primary ovarian insufficiency (POI) with
      reciprocal translocation between chromosomes 5 and 13. METHODS: Chromosomal
      analysis (G-banding) of a 39-year-old woman with elevated gonadotropin levels and
      secondary amenorrhea and review of the literature with a special focus on
      disrupted genes at the reported breakpoints. RESULTS: A reciprocal translocation
      between the long arms of chromosomes 5 and 13 was identified in the patient
      (46,XX,t(5;13)(q13;q14)). Investigation of the breakpoints revealed that the
      13q14.1 region encompasses FOXO1 (forkhead box 1) gene, which has an important
      role in granulosa cell function and follicle maturation. CONCLUSIONS: Autosomal
      translocations are rare in women with POI. We have reported the first case of a
      de novo reciprocal translocation involving chromosomes 5 and 13 in a POI patient.
      As one of the breakpoints encompasses the FOXO1 gene, it seems that disruption of
      this gene can be the cause of POI in this patient. This provides further evidence
      on the role of autosomal translocations in disrupting POI-associated genes.
      Therefore, concentrating on the genes at the breakpoints will be helpful to
      delineate the new biological pathways or genes involved in POI pathogenesis.

PMID- 28453299
TI  - Proposed biosimilar pegfilgrastim (LA-EP2006) compared with reference
      pegfilgrastim in Asian patients with breast cancer: an exploratory comparison
      from two Phase III trials.
AB  - AIM: This is a pooled subgroup analysis of Asian patients enrolled in two Phase
      III confirmatory studies comparing proposed biosimilar LA-EP2006 with reference
      pegfilgrastim in women receiving chemotherapy for breast cancer. PATIENTS &
      METHODS: Women were randomized to LA-EP2006 (n = 90) or reference (n = 84)
      pegfilgrastim (Neulasta(r), Amgen, Inc., CA, USA) for <=6 cycles of TAC
      chemotherapy. Primary end point was duration of severe neutropenia during Cycle 1
      (number of consecutive days with absolute neutrophil count <0.5 * 109/l) with
      equivalence confirmed if 95% CIs were within a +/-1-day margin. RESULTS: Mean
      duration of severe neutropenia (days) in Cycle 1 was 1.36 +/- 0.98 (LA-EP2006)
      versus 1.35 +/- 1.06 (reference) (difference 0.01 days; 95% CI: -0.30-0.32,
      indicating equivalence). CONCLUSION: LA-EP2006 showed similar clinical efficacy
      and safety compared with reference pegfilgrastim.

PMID- 28453300
TI  - Psychiatry, Sex, and Science: The Making of "Adolescent" Motherhood in Southern
      Brazil.
AB  - Research linking teen motherhood to psychoneurodevelopmental causes and
      pathologies has proliferated in the past two decades. In Brazil, a
      psychodevelopmental project of teen motherhood has gained traction despite many
      experts' long-standing commitment to psychodynamic psychiatry and social
      epidemiology, generating epistemic tension rather than substitution. Drawing on
      historical ethnography conducted in Southern Brazil, I explore how this project
      materialized through the co-production of epistemic struggles, remedial
      interventions, and ontological politics. In showing how this co-production became
      interwoven with incremental changes in young women's emotions, sexualities,
      relationships, and bodies, I describe how one particular "kind" of teen
      motherhood emerged and became entangled with both psychiatric knowledge
      production and the angst of working-class political agency. In giving women a
      contested psychiatric language with which to rework their social-moral worlds, I
      argue that science did more than conceptualize teen childbearing in pathological
      terms; it contributed to its troubled transformation.

PMID- 28453301
TI  - A comparison study of bioanalytical methods for detection and characterization of
      anti-velaglucerase alfa antibodies.
AB  - AIM: To provide more efficient and timely immunogenicity testing service to
      support routine patient care, the original complex testing algorithm for
      evaluation of anti-velaglucerase alfa antibodies has been simplified and
      individual methods (screen, confirm, titer, neutralizing antibody [NAb] and IgE)
      have been redeveloped/optimized and validated. RESULTS: To compare the
      performance of different methods, 50 velaglucerase alfa-treated patient samples
      were analyzed using both old and new methods for the presence of antidrug
      antibodies (ADAs) and 31 ADA-positive samples were analyzed for neutralizing
      capacity. The ADA and NAb statuses are almost identical from both methods and
      both ADA and NAb titer results are highly correlated with a Spearman's
      correlation of 0.96 and 0.86, respectively. CONCLUSION: The original and new
      testing methods can be considered interchangeable for the measurement of total
      and neutralizing anti-velaglucerase alfa antibodies.

PMID- 28453302
TI  - Variant in GALNT3 Gene Linked with Reduced Coronary Artery Disease Risk in
      Chinese Population.
AB  - Our previous study found expression of GALNT3 gene was reduced in coronary artery
      disease (CAD) patients, and it contributed to endothelial injury by regulating
      apoptosis and matrix metalloproteinase (MMP) expression. GALNT3 gene may be a
      potential target for future therapeutic intervention of CAD. However, none
      reports linking the GALNT3 gene to susceptibility of CAD. This study investigated
      the variant associations of GALNT3 gene and CAD. Thirteen single nucleotide
      polymorphism (SNP) in and around the GALNT3 gene were tagged and analyzed in CAD
      patients (n = 1515) and control individuals (n = 5019), and the SNPs with CAD
      were tested with multiple logistic regression analysis in an additive genetic
      model (with one degree of freedom) after adjusting for age and sex. Expression of
      GALNT3 gene was detected by real-time PCR and Western blot. Luciferase reporter
      assays were used to detect the allele-specific effect of rs4621175 on
      transcriptional activity. Two GALNT3 markers, rs13427924 and rs4621175, were
      significantly associated with CAD (odds ratio [OR] = 0.87, p = 1.01 * 10-3 and OR
      = 0.75, p = 2.51 * 10-4, respectively), and the risk A allele of rs4621175 was
      associated with lower GALNT3 expression in both mRNA and protein level; also, A
      allele showed decreased reporter activity. In addition, we found the level of
      GALNT3 negatively correlated with MMP-2 gene expression. This study identified
      GALNT3 as a novel gene that rendered patients susceptible to CAD, and the A
      allele of a disease-associated variant rs4621175 linked reduced CAD risk through
      decreased GALNT3 expression. These results confirmed the role of GALNT3 gene in
      CAD and provided new insights into the genetic regulation of the GALNT3 gene with
      respect to the pathogenesis of CAD.

PMID- 28453303
TI  - Corrigendum.

PMID- 28453304
TI  - Mold allergy: is it real and what do we do about it?
AB  - INTRODUCTION: fungi produce substances that contain pathogen-associated molecular
      patterns (pamps) and damage-associated molecular patterns (damps) which bind to
      pattern recognition receptors, stimulating innate immune responses in humans.
      they also produce allergens that induce production of specific ige. Areas
      covered: In this review we cover both innate and adaptive immune responses to
      fungi. Some fungal products can activate both innate and adaptive responses and
      in doing so, cause an intense and complex health effects. Methods of testing for
      fungal allergy and evidence for clinical treatment including environmental
      control are also discussed. In addition, we describe controversial issues
      including the role of Stachybotrys and mycotoxins in adverse health effects.
      Expert commentary: Concerns about long-term exposure to fungi have led some
      patients, attorneys and fungus advocates to promote fears about a condition that
      has been termed toxic mold syndrome. This syndrome is associated with vague
      symptoms and is believed to be due to exposure to mycotoxins, though this
      connection has not been proven. Ultimately, more precise methods are needed to
      measure both fungal exposure and the resulting health effects. Once that such
      methods become available, much of the speculation will be replaced by knowledge.

PMID- 28453305
TI  - A Clinician Guide to Altitude Training for Optimal Endurance Exercise Performance
      at Sea Level.
AB  - Constantini, Keren, Daniel P. Wilhite, and Robert F. Chapman. A clinician guide
      to altitude training for optimal endurance exercise performance at sea level.
      High Alt Med Biol. 18:93-101, 2017.-For well over 50 years, endurance athletes
      have been utilizing altitude training in an effort to enhance performance in sea
      level competition. This brief review will offer the clinician a series of
      evidence-based best-practice guidelines on prealtitude and altitude training
      considerations, which can ultimately maximize performance improvement outcomes.

PMID- 28453306
TI  - The Association of Lung Clearance Index with COPD and FEV1 Reduction in 'Men Born
      in 1914'.
AB  - Lung Clearance Index (LCI) provides an overall measurement of ventilation
      inhomogeneity. This population-based study examines whether LCI predicts
      pulmonary obstruction and incidence of chronic obstructive pulmonary disease
      (COPD) events over a long-term follow-up. Multiple breath nitrogen washout and
      spirometry were performed in 674 men from the cohort "Men born in 1914" at age 55
      years. Subjects were classified into quartiles (Q) of LCI and according to LCI
      above and below upper limit of normal (ULN). Incidence of COPD events (COPD
      hospitalisations or COPD-related deaths) were monitored over the remaining life
      span of the men, by linkage with national hospital registers. In addition,
      development of pulmonary obstruction (i.e., FEV1/vital capacity below lower limit
      of normal (LLN)) was studied in 387 men who were re-examined with spirometry at
      68 years of age. Over 44 years of follow-up, there were 85 incident COPD events.
      Hazards ratios (HRs) for COPD across quartiles of LCI were: Q1 1.00 (reference),
      Q2 1.30 (95% confidence interval: 0.61-2.74), Q3 1.97 (0.97-3.98) and Q4 3.99
      (2.06-7.71) (p value for trend <0.001). This relationship remained significant
      after adjustments for confounding factors, including smoking and FEV1 (HR, Q4 vs
      Q1: 2.34 (1.17-4.69); p value for trend: 0.006). Reduction of FEV1 between 55 and
      68 years of age and incidence of pulmonary obstruction was highest in those with
      high LCI. High LCI is associated with future development of pulmonary obstruction
      and incidence of COPD hospitalisations in men from the general population.

PMID- 28453307
TI  - -643C > T RANKL gene polymorphism is associated with osteoporosis in Tunisian
      postmenopausal women.
AB  - OBJECTIVES: The dynamic nature of the skeleton is achieved by a remodeling
      process. Receptor activator of nuclear factor kappa B (RANK) ligand (RANKL)
      stimulates bone resorption by activating RANK signaling. Therefore it is
      considered as a candidate gene regulating susceptibility to osteoporosis. In the
      current study, we have investigated the association between the RANKL gene -693G
      > C and -643 C > T polymorphisms and bone mineral density (BMD) in a population
      of postmenopausal Tunisian women. METHODS: Polymorphic sites in RANKL gene
      (rs9533155 -693G > C and rs9533156 -643 C > T polymorphisms) were determined
      using PCR-RFLP analysis in 566 postmenopausal Tunisian women. All statistical
      analysis were examined by SPSS software. RESULTS: We have detected a significant
      difference in lumbar spine and hip BMD for -643C > T genotypes. For -693G > C
      genotypes, a significant difference was detected only in hip BMD. The
      distribution of -643C > T genotypes and alleles between three groups
      (osteoporotic, osteopenic and normal women) revealed a significant association of
      the TT genotype with development of osteoporosis (p = 0.01; odds ratio 2.15),
      although for the -693G > C polymorphism, no significant results were found.
      CONCLUSION: We have demonstrated the association of the -643C > T polymorphism
      with BMD variation and osteoporosis risk in postmenopausal Tunisian women.

PMID- 28453308
TI  - Genitourinary syndrome of menopause in five Asian countries: results from the Pan
      Asian REVIVE survey.
AB  - OBJECTIVES: The Pan-Asian REVIVE survey aimed to examine women's experiences with
      genitourinary syndrome of menopause (GSM) and their interactions with health-care
      professionals (HCPs). METHODS: Self-completed surveys were administered face-to
      face to 5992 women (aged 45-75 years) in Indonesia, Malaysia, Singapore, Taiwan,
      and Thailand. RESULTS: Of 638 postmenopausal women with GSM symptoms, only 35%
      were aware of the GSM condition, most of whom first heard of GSM through their
      physician (32%). The most common symptoms were vaginal dryness (57%) and
      irritation (43%). GSM had the greatest impact on sexual enjoyment (65%) and
      intimacy (61%). Only 25% had discussed their GSM symptoms with a HCP, and such
      discussions were mostly patient-initiated (64%) rather than HCP-initiated (24%).
      Only 21% had been clinically diagnosed with GSM and only 24% had ever used
      treatment for their symptoms. Three-quarters of those who had used treatment for
      GSM had discussed their symptoms with a HCP compared to only 9% of those who were
      treatment-naive. CONCLUSION: GSM is underdiagnosed and undertreated in Asia. As
      discussion of GSM with HCPs appears to be a factor influencing women's awareness
      and treatment status, a more active role by HCPs to facilitate early discussions
      on GSM and its treatment options is needed.

PMID- 28453309
TI  - Combination of Cyclodextrin and Ionic Liquid in Analytical Chemistry: Current and
      Future Perspectives.
AB  - The growth in driving force and popularity of cyclodextrin (CDs) and ionic
      liquids (ILs) as promising materials in the field of analytical chemistry has
      resulted in an exponentially increase of their exploitation and production in
      analytical chemistry field. CDs belong to the family of cyclic oligosaccharides
      composing of alpha-(1,4) linked glucopyranose subunits and possess a cage-like
      supramolecular structure. This structure enables chemical reactions to proceed
      between interacting ions, radical or molecules in the absence of covalent bonds.
      Conversely, ILs are an ionic fluids comprising of only cation and anion often
      with immeasurable vapor pressure making them as green or designer solvent. The
      cooperative effect between CD and IL due to their fascinating properties, have
      nowadays contributed their footprints for a better development in analytical
      chemistry nowadays. This comprehensive review serves to give an overview on some
      of the recent studies and provides an analytical trend for the application of CDs
      with the combination of ILs that possess beneficial and remarkable effects in
      analytical chemistry including their use in various sample preparation techniques
      such as solid phase extraction, magnetic solid phase extraction, cloud point
      extraction, microextraction, and separation techniques which includes gas
      chromatography, high-performance liquid chromatography, capillary electrophoresis
      as well as applications of electrochemical sensors as electrode modifiers with
      references to recent applications. This review will highlight the nature of
      interactions and synergic effects between CDs, ILs, and analytes. It is hoped
      that this review will stimulate further research in analytical chemistry.

PMID- 28453311
TI  - Provisional drivers' perceptions of the impact of displaying P plates.
AB  - OBJECTIVE: P plates (or decals) identify a driver's license status to other road
      users. They are a compulsory part of the graduated driver licensing system in
      Queensland, Australia, for drivers on a P1 (provisional 1) or P2 (provisional 2)
      license. This study explored the perceptions of young drivers regarding the
      display of P plates (decals) in Queensland, Australia. METHODS: In this study,
      226 young drivers with a provisional (intermediate/restricted) license completed
      a 30-min online survey between October 2013 and June 2014. t Tests were used to
      compare the opinions of people who displayed their plates nearly always with
      those who displayed them less frequently. RESULTS: Participants approved of the
      requirement to display P plates with 69% of those on a P1 license and 79% on a P2
      license supporting the condition to display P1 (red) plates. Participants on a P1
      license (62%) and a P2 license (68%) also approved the requirement to display P2
      (green) plates. However, young drivers also perceived that the display of P
      plates (measured from 1 = never to 5 = nearly all the time) enabled newly
      licensed drivers to be targeted by police and other drivers (those who do not
      always display P plates: M = 3.72, SD = 0.94; those who nearly always display P
      plates: M = 3.43, SD = 1.09). CONCLUSIONS: The study findings suggest that
      participants who nearly always display their P plates are more likely to report
      that having to display their plates resulted in them driving more carefully.

PMID- 28453310
TI  - Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and
      other chronic diseases?
AB  - Menopausal disorders may include shorter-term symptoms, such as hot flushes and
      night sweats (vasomotor symptoms, VMS) and longer-term chronic conditions such as
      cardiovascular disease (CVD), osteoporosis, and cognitive impairment. Initially,
      no clear link between the shorter-term symptoms and longer-term chronic
      conditions was evident and these disorders seemed to occur independently from
      each other. However, there is a growing body of evidence demonstrating that VMS
      may be a biomarker for chronic disease. In this review, the association between
      VMS and a range of chronic postmenopausal conditions including CVD, osteoporosis,
      and cognitive decline is discussed. Prevention of CVD in women, as for men,
      should be started early, and effective management of chronic disease in
      postmenopausal women has to start with the awareness that VMS during menopause
      are harbingers of things to come and should be treated accordingly.

PMID- 28453312
TI  - Educating Healthcare Providers About Breastfeeding: Something for Everyone.

PMID- 28453313
TI  - Medical adhesive-related skin injuries associated with vascular access.
AB  - Establishing vascular access and preventing infection, both at insertion and
      during ongoing care is generally the top priority; the maintenance of optimal
      skin integrity is often a distant secondary consideration. Skin can react to
      different types of dressings or adhesives, or problems can arise relating to the
      securement of lines or the development of sensitivities to cleaning solutions.
      Clearly, these scenarios are not limited to the securement of vascular access
      devices; however, a patient with a long-term vascular access device may not have
      other options for vascular access, which makes this a very important and yet
      largely unrecognised area. A review of the limited literature that existed up to
      March 2015 showed it was typically concerned with skin tears connected with
      dressings and removal, and contact irritant dermatitis. The tissue viability team
      and vascular access team reviewed the current products associated with a typical
      vascular access dressing to ensure it was fit for purpose and where at all
      possible had good scientific literature for validation. The team worked
      proactively to recognise those patients at risk with the early identification of
      potential medical adhesive-related skin injuries (MARSI). To facilitate this an
      algorithm was developed that offers a step-by-step approach, clearly outlining
      what to do to prevent MARSI and its treatment should it develop. These reactions
      can result from other factors than the dressing alone, and an increase in these
      kinds of skin reaction in patients who are on chemotherapy regimens is being
      explored further. Through the implementation of an algorithm, education for both
      staff and patients and collaborative working between vascular access and tissue
      viability teams, a reduction in these phenomena has been seen despite an
      increasing number of at-risk patients.

PMID- 28453314
TI  - Using audits as evidence.

PMID- 28453315
TI  - The implementation of the Vessel Health and Preservation framework.
AB  - Vascular access is an important component of health care but is not without
      associated risks, some of which can be life-threatening. The Vessel Health and
      Preservation (VHP) framework was developed with the intention of providing
      frontline staff with a resource to assist in assessing and selecting the best
      vascular access device to meet individual patient needs and to preserve veins for
      future use. This article examines the impact of the introduction of the framework
      into a haematology ward in an acute hospital in the North West of England during
      a 3-month pilot study. The results indicate that the VHP framework gave nursing
      staff more autonomy to choose the appropriate vascular access device for their
      patients and improved staff knowledge around pH and osmolality of intravenous
      drugs. However it is clear that more in-depth evaluations need to be conducted to
      assess the impact of VHP on patient care and outcomes.

PMID- 28453316
TI  - Peripheral intravenous cannulation: protecting patients and nurses.
AB  - Peripheral intravenous cannulation is a common clinical procedure in today's
      healthcare setting. There are a range of different devices to choose from, and
      this article will consider the risk of catheter-related bloodstream infections
      and needlestick injuries, national and international guidelines on infection
      prevention and safety in intravenous access, the need for closed catheters,
      features of the Introcan Safety(r) 3 (B. Braun Melsungen AG) and research into
      peripheral cannulas.

PMID- 28453317
TI  - Runner up 2017.

PMID- 28453318
TI  - Views from the front line: is the NHS workforce at crisis point?
AB  - Emeritus Professor Alan Glasper, from the University of Southampton, discusses a
      report revealing that hospital doctors are concerned about their ability to
      deliver safe patient care over the next 12 months.

PMID- 28453319
TI  - Does a checklist reduce the number of errors made in nurse-assembled discharge
      prescriptions?
AB  - BACKGROUND: The safe supply of medicines is an integral part of being discharged
      from hospital. Locally, nurses are responsible for assembling medication for
      discharge prescriptions. Over a 2-year period 15 serious medication errors
      relating to discharge were reported on the health and ageing unit. This project
      was designed to evaluate whether a discharge medication checklist could reduce
      errors on nurse-assembled discharge prescriptions. METHODS AND RESULTS: A
      baseline audit was conducted to identify the number of medication errors on nurse
      assembled discharge prescriptions. After the audit period the discharge
      medication checklist was introduced and education and training was provided to
      nursing staff. There was a statistically significant reduction in the number of
      assembled discharge prescriptions with one or more errors (28/56 vs. 9/44;
      p=0.0478) when re-audited. CONCLUSION: The introduction of a discharge medication
      checklist demonstrated a significant reduction in errors. The authors recommend
      that the discharge medication checklist and training programme be rolled out
      across medical wards to facilitate safe discharge.

PMID- 28453320
TI  - Reforming the approach to clinical negligence in the NHS.
AB  - John Tingle, Reader in Health Law at Nottingham Trent University, discusses
      proposals for the introduction of a Rapid Resolution and Redress Scheme for
      families affected by severe avoidable birth injury.

PMID- 28453321
TI  - Hand decontamination in clinical practice: a review of the evidence.
AB  - Hand decontamination is known to significantly reduce the spread of hospital
      acquired infections but, despite a wealth of guidelines and education campaigns,
      evidence suggests that many healthcare workers are non-compliant with hand
      decontamination. The behaviours that prevent hand decontamination are complex.
      Studies look at attitudes towards dirt, disgust, self-protective hand washing and
      familiarity with patients. Self-protection behaviours manifest themselves in
      washing hands more often after certain tasks. Professional issues are also
      reported to have an impact on hand decontamination, mainly lack of time, heavy
      workloads, understaffing and frequency of admissions to the clinical area.
      Further research needs to be undertaken to include comparison between self
      reported studies and observational studies, as it has been shown that healthcare
      workers may rationalise their behaviour and that self-reporting can be
      unreliable.

PMID- 28453322
TI  - Diversity at the heart of care.

PMID- 28453323
TI  - The management and treatment of hyperkeratosis.
AB  - Rebecca Elwell, Macmillan Lymphoedema Advanced Nurse Practitioner, Royal Stoke
      University Hospital, discusses recommendations on management of this skin
      problem, which may co-occur with chronic oedema.

PMID- 28453324
TI  - Things must change.

PMID- 28453325
TI  - Implementing smart infusion pumps with dose-error reduction software: real-world
      experiences.
AB  - Intravenous (IV) drug administration, especially with 'smart pumps', is complex
      and susceptible to errors. Although errors can occur at any stage of the IV
      medication process, most errors occur during reconstitution and administration.
      Dose-error reduction software (DERS) loaded on to infusion pumps incorporates a
      drug library with predefined upper and lower drug dose limits and infusion rates,
      which can reduce IV infusion errors. Although this is an important advance for
      patient safety at the point of care, uptake is still relatively low. This article
      discuses the challenges and benefits of implementing DERS in clinical practice as
      experienced by three UK trusts.

PMID- 28453326
TI  - Management of foreign body ingestions in children: button batteries and magnets.
AB  - Foreign body ingestion and foreign body aspiration commonly affect young children
      between 6 months and 6 years. A large number of these events remain unwitnessed
      and asymptomatic while the swallowed foreign body traverses the gastrointestinal
      tract and is passed in the stool. Recent literature has shown an increase in
      morbidity associated with button battery and (neomydium) magnet ingestions in
      children, particularly over the last decade. Early identification and management
      in a time critical manner is required in cases where button batteries get lodged
      in the oesophagus or multiple magnets are swallowed. Deaths, although rare, have
      been reported with these dangerous foreign body ingestions in children where
      diagnoses were delayed. Nurses through their direct contact with children in
      different clinical settings play a vital role in managing foreign body
      ingestions.

PMID- 28453327
TI  - From staff nurse to nurse consultant.

PMID- 28453328
TI  - Securement for vascular access devices: looking to the future.

PMID- 28453329
TI  - Modernising patient clothing: a Florence Nightingale Foundation project.
AB  - Christine Fitzgerald, Matron at The Hillingdon Hospitals NHS Foundation Trust
      (currently on secondment) discusses a project to boost patient self-esteem and
      dignity through the clothing provided for them to wear.

PMID- 28453330
TI  - Resurgence of measles and mumps: not just a childhood problem.

PMID- 28453331
TI  - Changing lives-it starts with a plan.
AB  - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, discusses how
      nurse leaders can influence the Sustainability and Transformation Plan for the
      benefit of their local area population.

PMID- 28453332
TI  - Long-Term Intermittent Exposure to High Altitude Elevates Asymmetric
      Dimethylarginine in First Exposed Young Adults.
AB  - Luneburg, Nicole, Patricia Siques, Julio Brito, Juan Jose De La Cruz, Fabiola
      Leon-Velarde, Juliane Hannemann, Cristian Ibanez, and Rainer Boger. Long-term
      intermittent exposure to high altitude elevates asymmetric dimethylarginine in
      first exposed young adults. High Alt Med Biol. 18:226-233, 2017.-Hypoxia-induced
      dysregulation of pulmonary and cerebral circulation may be related to an impaired
      nitric oxide (NO) pathway. We investigated the effect of chronic intermittent
      hypobaric hypoxia (CIH) on metabolites of the NO pathway. We measured asymmetric
      and symmetric dimethylarginine (ADMA and SDMA) and monomethyl-L-arginine (L-NMMA)
      and assessed their associations with acclimatization in male draftees (n = 72)
      undergoing CIH shifts at altitude (3550 m) during 3 months. Sixteen Andean
      natives living at altitude (3675 m) (chronic hypobaric hypoxia [CH]) were
      included for comparison. In CIH, ADMA and L-NMMA plasma concentrations increased
      from 1.14 +/- 0.04 to 1.95 +/- 0.09 MUmol/L (mean +/- SE) and from 0.22 +/- 0.07
      to 0.39 +/- 0.03 MUmol/L, respectively, (p < 0.001 for both) after 3 months,
      whereas SDMA did not change. The concentrations of ADMA and L-NMMA were higher in
      CH (3.48 +/- 0.07, 0.53 +/- 0.08 MUmol/L; p < 0.001) as compared with CIH. In
      both CIH and CH, ADMA correlated with hematocrit (r2 = 0.07, p < 0.05; r2 = 0.26;
      p < 0.01). In CIH, an association of ADMA levels with poor acclimatization status
      was observed. We conclude that the endogenous NO synthase inhibitors, ADMA and L
      NMMA, are elevated in hypoxia. This may contribute to impaired NO production at
      altitude and may also be predictive of altitude-associated health impairment.

PMID- 28453333
TI  - Leaving no-one behind: using assistive technology to enhance community living for
      people with intellectual disability.

PMID- 28453334
TI  - Different Immune Signature in Youths Experiencing Antipsychotic-Induced Weight
      Gain Compared to Untreated Obese Patients.
AB  - OBJECTIVES: To assess cytokine and chemokine levels in youth experiencing
      antipsychotic-induced weight gain (AIWG) compared to obese patients,
      hypothesizing a different "immune signature" between the two kinds of obesity.
      METHODS: We compared a group of youth experiencing AIWG (N 19, mean age 159
      months, mean body mass index [BMI] z-score 1.81) and an age-, gender-, and BMI
      matched group of untreated obese patients (N 19, mean age 147 months, mean BMI z
      score 2) for a wide range of cytokines and chemokines by using a multiplex ELISA
      test. RESULTS: Platelet-derived growth factor (PDGF), interleukin (IL)1-beta,
      IL4, IL8, IL9, IL12, IL 17, eotaxin, FGF, GMCSF, IP10, MIP1b, and vascular
      endothelial growth factor (VEGF) were significantly lower in the AIWG group,
      whereas IL13 and RANTES were significantly higher. Controlling for age, sex, and
      BMI, PDGF, IL4, IL8, IL13, IL17, eotaxin, fibroblast growth factor (FGF),
      granulocyte-macrophage colony-stimulating factor (GMCSF), IP10, MIP1b, and VEGF
      remain significantly different. CONCLUSION: A clearly different pattern of
      cytokines distinguishes the two kinds of obesity, suggesting a different immune
      signature. Interestingly, most of the cytokines and chemokines bearing
      proinflammatory effects resulted decreased in the AIWG group, whereas IL-13,
      which holds an immune-modulatory effect, resulted increased.

PMID- 28453336
TI  - The Relationship Between the Intercrease Line and the A1 Digital Pulley: A
      Cadaveric Study.
AB  - BACKGROUND: Accurate identification of surface anatomy is critical to identify
      the location of the A1 pulley. The intercrease line (ICL) describes a transverse
      line between the radial edge of the proximal palmar crease and the ulnar edge of
      the distal palmar crease. We hypothesize that this easily identifiable surface
      landmark approximates the location of the A1 pulley. METHODS: The ICL was marked
      on 7 cadaver hands. We marked a point proximal to the proximal digital crease
      (PDC) equal to the distance between each digit's proximal interphalangeal crease
      (PIC) and PDC (the PIC/PDC point). We calculated the distance between PIC/PDC
      points and proximal edge of the A1 pulleys. RESULTS: The ICL was proximal to A1
      in all digits. The PIC/PDC point was distal to A1 in the ring finger, and
      proximal to A1 in the index, middle, and small fingers. The PIC/PDC point was
      closer to the A1 pulley than the ICL in the middle and ring fingers. CONCLUSIONS:
      Despite less accuracy than the PIC/PDC point at approximating the location of the
      A1 pulley, the ICL is reliably proximal to the A1 pulley.

PMID- 28453337
TI  - Venous Bridge Arterial Grafting for Thumb Replantation.
AB  - BACKGROUND: The purpose of this study is to describe a novel technique using an
      interposition vein graft for thumb replantation in these severe avulsion
      injuries. METHODS: From 2002 to 2012, 8 patients underwent interposition venous
      bridge grafting from the dorsal radial artery at the anatomic snuffbox to the
      ulnar digital artery of the thumb. All patients had a traumatic thumb amputation
      with a severe injury to the ulnar digital artery. The technique began with bony
      stabilization; the radial artery at the anatomic snuffbox is exposed, vein graft
      harvested, and microsurgical end-to-side (proximally) and end-to-end (distally)
      anastomoses are carried out. RESULTS: The average time to the operating room was
      7.4 hours and time to reperfusion was 9.5 hours. At 3.1 years of follow-up, all 8
      thumbs remained viable, without any need for revision procedures. The only
      complication was a metacarpal shaft nonunion treated successfully with iliac
      crest bone grafting. At last follow-up, all patients reported no or mild pain,
      with an average metacarpophalangeal (MCP) range of motion of 46.5 degrees , and
      intact but diminished 2-point discrimination. All patients were able to return to
      work full-time. CONCLUSIONS: Due to the challenging nature of thumb avulsion
      injuries and the pronated position of the thumb, novel salvage alternatives are
      important. We describe a technique when no proximal vessels are available, using
      a vein to bridge the dorsal radial artery to the ulnar digital artery of the
      thumb. This novel arterial reconstruction has shown promise in thumb replantation
      associated with severe avulsion injuries.

PMID- 28453338
TI  - The Stener Lesion: Historical Perspective and Evolution of Diagnostic Criteria.
AB  - BACKGROUND: In 1962, Bertil Stener first described the anatomy and treatment of
      the displaced ulnar collateral ligament of the metacarpophalangeal joint, later
      called the Stener lesion. Since Stener's publication, treatment algorithms for
      ulnar collateral ligament rupture have aided in preoperative diagnosis, yet the
      best diagnostic method to assess ligament displacement remains largely undefined.
      METHODS: An extensive literature search was performed to explore the treatment
      evolution of the Stener lesion and explore how technical development has
      influenced Stener lesion diagnosis. We also sought to illuminate the life and
      work of Bertil Stener. RESULTS: Studies evaluating the use of magnetic resonance
      imaging (MRI) and ultrasound (US) technology have suggested that these modalities
      have improved Stener lesion diagnosis. CONCLUSION: Despite the utility of
      developing MRI and US technology, consensus for one superior diagnostic tool for
      Stener lesions does not currently exist.

PMID- 28453339
TI  - The Painful Sacrifice: The Epidemiology of Hand Injuries During the Holy
      Festivals in the Sultanate of Oman-A 10-Year Case-Control Study.
AB  - BACKGROUND: The human hand is an important functional and sensory organ. Its
      complex anatomy reflects its important functional capabilities. Many Muslim
      countries observe the holy festivals with a traditional sacrifice of an animal in
      order to share the meat (basic commodity) with beloved ones. During such
      festivals hand injuries have been reported to increase. This study aimed to
      compare cases and controls of hand injuries treated at the national trauma center
      in the Sultanate of Oman during a 10-year time period. METHODS: This is a case
      control retrospective review for 10 years in the Sultanate of Oman. The cases
      were all hand injuries registered and assessed at Khoula Hospital in the
      Sultanate of Oman during the 3 days of both holy festivals from January 2004 to
      December 2013. Controls were hand injuries registered and assessed at Khoula
      Hospital in the Sultanate of Oman during nonfestival days. Data were extracted
      and collected from the Emergency Department database. A descriptive and
      comparative analysis was done. RESULTS: There were 1091 cases reviewed in this
      study. Knife laceration was 2.4 more common during holy festivals than any other
      time. Extensor tendon injuries were 2.7 more common during holy festivals than
      nonfestival times. Thumb and index fingers constituted around 40% of the total
      injuries. Of all patients reviewed, 85% were treated and discharged home without
      admission. CONCLUSION: Holy festivals in the sultanate of Oman are risky times
      for hand injuries. Knife lacerations are more common during such times than any
      other times. Emergency and plastic services should be aware of the pattern of
      hand injuries during such times in order to prepare and plan services
      accordingly.

PMID- 28453340
TI  - Prospective Randomized Trial Comparing the Efficacy of Surgical Preparation
      Solutions in Hand Surgery.
AB  - BACKGROUND: Decontamination of the skin prior to incision is part of the standard
      of care for any surgical procedure. Previous studies have demonstrated variable
      efficacy of different surgical preparation solutions based on anatomic location.
      The purpose of this study is to determine the effectiveness of 3 commonly used
      surgical preparation solutions in eliminating bacteria from the skin prior to
      incision for common elective soft tissue hand procedures. METHODS: A total of 240
      patients undergoing clean, elective, soft tissue hand surgery were prospectively
      randomized to 1 of 3 groups (ChloraPrep, DuraPrep, or Betadine). Prepreparation
      and postpreparation cultures were obtained adjacent to the surgical incision and
      neutralization was performed on the obtained specimen. Cultures were held for 14
      days and patients followed for 6 weeks postoperatively. RESULTS: Postpreparation
      cultures were positive in 21 of 80 (26.3%) ChloraPrep patients, 3 of 79 (3.8%)
      DuraPrep patients, and 1 of 81 (1.2%) Betadine patients ( P < .001). There was no
      difference in the postpreparation culture rate between DuraPrep and Betadine ( P
      = 1.000). CONCLUSIONS: Duraprep and Betadine were found to be superior to
      Chloraprep for skin decontamination prior to clean elective soft tissue hand
      surgery. The bacterial flora of the hand was found to be different from those of
      the shoulder and spine. The clinical significance of this finding requires
      clinical consideration because the majority of prepreparation and postpreparation
      positive cultures were of Bacillus species, which are rarely a cause of
      postoperative infections.

PMID- 28453341
TI  - The Scaphoid Staple: A Systematic Review.
AB  - BACKGROUND: The purpose of this systematic review is to analyze the indications,
      outcomes, and complications of scaphoid fixation with a staple. METHODS: The
      literature was reviewed for all cases of the scaphoid staple. Five articles
      including 188 patients, of 77 primary scaphoid fractures and 111 other
      indications that included delayed union, nonunion, and avascular necrosis, were
      reviewed. Demographic data, outcomes, and complications were recorded. RESULTS:
      The union rate of the scaphoid staple is 94.7%, and 95.7% of patients return to
      work after an average of 9.8 weeks after a 4.7-week period of immobilization. The
      complication rate was 9.0%, and 7.5% required hardware removal. Clinical and
      radiographic healing was higher in primary fractures as compared with other
      indications. Other indications, as compared with primary fracture, had a higher
      rate of hardware removal. CONCLUSIONS: For all indications, the scaphoid staple
      has a high union rate and a low complication rate. In the authors' experience,
      the procedure is fast, not technically challenging, and may be considered for
      primary fracture, delayed union, nonunion, and avascular necrosis of the
      scaphoid.

PMID- 28453342
TI  - Flexor Tendon Rupture Due to Previously Undiagnosed Kienbock Disease: A Case
      Report.
AB  - BACKGROUND: Spontaneous flexor tendon rupture is rare and most common in the
      little finger. The pathogenesis of spontaneous tendon ruptures is unclear but may
      occur through attrition or mechanical abrasion over a bony prominence. Kienbock
      disease is avascular necrosis of the lunate, with an unknown etiology. METHODS:
      We present a case of spontaneous rupture of flexor digitorum profundus due to
      Kienbock disease, which we believe is the first recorded case of flexor tendon
      rupture attributable to osteonecrosis of the lunate. RESULTS: The patient
      underwent single-stage reconstruction of FDP and regained a good range of motion
      at the affected DIPJ. CONCLUSIONS: This case illustrates the the importance of
      plain radiographs in the assessment of a patient presenting with spontaneous
      flexor tendon rupture in the hand to exclude bony pathology as a cause.

PMID- 28453343
TI  - Acute Isolated Flexor Tendon Laceration Associated With a Distal Radius Fracture.
AB  - BACKGROUND: Subacute rupture of the flexor tendons secondary to distal radius
      fractures is well documented. Recently, accounts of flexor tendon rupture
      following open reduction internal fixation have been associated with volar plate
      fixation. However, discovery of an occult traumatic flexor tendon laceration
      during fixation of an acute distal radius fracture is not well described. This
      case indicates the importance of careful preoperative and intraoperative
      examination of the flexor tendons in the setting of comminuted distal radius
      fractures. METHODS: A forty-seven-year-old male sustained a comminuted, dorsally
      displaced distal radius fracture. Initial and post-reduction examinations
      revealed no gross functional abnormalities. Upon operative fixation of the
      fracture, laceration of the flexor digitorum profundus (FDP) tendon to the index
      finger was incidentally noted at the level of the fracture site. RESULTS: Due to
      extensive dorsal comminution, shortening, and the presence of a lunate facet
      fragment, we performed volar fragment-specific and dorsal spanning bridge plate
      fixation. The proximal and distal ends of the FDP tendon were marked, but repair
      was deferred until implant removal. This allowed for proper informed consent and
      avoided potential compromise of the repair given the presence of a volar implant.
      CONCLUSIONS: Acute flexor tendon rupture secondary to closed distal radius
      fractures may go unnoticed if a high index of suspicion is not maintained.
      Delayed diagnosis of these ruptures convolutes the mechanism of injury and
      disrupts the recovery process. Hand surgeons should be vigilant in examining
      flexor tendon function during the preoperative evaluation, especially in the
      setting of acute high-energy injury.

PMID- 28453345
TI  - Absorption-Dependent Negative Friction Coefficients in Tendon-Sheath Excursion.

PMID- 28453344
TI  - Pediatric Hereditary Angioedema as a Cause of Acute Compartment Syndrome of the
      Hand and Forearm: A Case Report.
AB  - BACKGROUND: Compartment syndrome of the upper extremity is a surgical emergency
      that, when left untreated, can have dire consequences. Its causes are numerous,
      one of which is the uncommon entity hereditary angioedema, an autosomal dominant
      disease resulting in edema in a variety of potential locations, including the
      extremities. This is only the second time hereditary angioedema has been
      mentioned in the literature as a cause of compartment syndrome. METHODS: We
      present a case of hereditary angioedema leading to hand and forearm compartment
      syndrome in a 13-year-old pediatric patient. Diagnosis of hereditary angioedema
      was made by our Rheumatology colleagues with physical exam and a thorough
      history, and confirmed by laboratory studies. RESULTS: Our patient presented with
      compartment syndrome of the hand and forearm and underwent hand and volar forearm
      fasciotomies. She was subsequently worked up for hereditary angioedema with
      laboratory results confirming the diagnosis. She was discharged after a 5-day
      hospitalization with prophylactic C1-inhibitor therapy. CONCLUSIONS: Hereditary
      angioedema is a rare but known cause of compartment syndrome of the upper
      extremity, and must be considered when patients present with compartment syndrome
      of unknown etiology. This disease can be diagnosed by laboratory studies and
      symptoms can be controlled with medical therapy.

PMID- 28453346
TI  - Outcomes of Surface Replacement Proximal Interphalangeal Joint Arthroplasty
      Through a Volar Approach: A Prospective Study.
AB  - BACKGROUND: The dorsal approach to the proximal interphalangeal (PIP) joint
      provides the advantage of improved visualization of the articular surface, while
      the disadvantage of a dorsal approach is the disruption of the central slip and
      extensor mechanism requiring a delay in range of motion exercises. A volar
      approach keeps the central slip and extensor mechanism intact, allowing for early
      range of motion. The goal of this study was to evaluate patient outcomes of
      surface replacement (SR) PIP joint arthroplasty performed through a volar
      approach. METHODS: Twenty-one patients were evaluated with primary osteoarthritis
      of a single PIP joint and underwent SR arthroplasty using the Stryker SR PIP
      joint implants. Patients included in this study were exclusively treated through
      a volar approach. Preoperative range of motion, coronal plan deformity,
      Disabilities of the Arm, Shoulder and Hand (DASH), and patient satisfaction were
      measured and compared with postoperative measurements using a paired Student t
      test. RESULTS: The average length of follow-up was 34 months (+/- 9 months).
      Postoperative arc of motion for the PIP and distal interphalangeal (DIP) joints
      measured 87 degrees  (+/-12 degrees ) and 36 degrees  (+/-11 degrees ),
      respectively. The average improvement in PIP arc of motion was 58 degrees , DASH
      score measured 14 (+/-5), satisfaction measured 4 (+/-1), and coronal plane
      deviation measured 2 degrees  (+/-2 degrees ). No evidence of implant subsidence
      was found on postoperative radiographs. Four patients required an extensor tendon
      tenolysis, and 1 patient suffered a superficial surgical site infection.
      CONCLUSION: SR arthroplasty, when performed through a volar approach, allows for
      early range of motion and greater improvements in arc of motion, DASH score, and
      patient satisfaction.

PMID- 28453347
TI  - Drill Penetration Injury to Extensor Tendons: A Biomechanical Analysis.
AB  - BACKGROUND: Little is known about extensor tendon failure following drill injury
      at the time of volar plate fixation. Our goals were to analyze extensor tendon
      injury following simulated drill penetration, and change in tendon displacement
      during cyclic loading following simulated drill penetration injury. METHODS:
      Extensor pollicis longus (EPL) and extensor carpi radialis brevis (ECRB) tendons
      were harvested from 9 fresh frozen cadaveric arms. Eighteen EPL and 18 ECRB
      samples were created from harvested tendons. Drill penetration injury was
      performed in either a continuous or an oscillating mode. Injured tendons were
      subjected to 1200 cycles at 1- to 15-kg cyclic load at a frequency of 1 Hz, and
      analyzed for failure at drill sites and change in displacement throughout the
      testing cycle. RESULTS: Ten EPL samples and 16 ECRB samples completed testing
      without failure. Tendon type (ECRB, EPL), mode of injury (continuous,
      oscillating), and location (proximal, distal) did not affect tendon displacement
      during loading. A single EPL tendon failed following continuous drill penetration
      injury. Extensor carpi radialis brevis samples had a mean change in displacement
      of 2.8 (standard deviation [SD]: 1.5 mm) and 5.9 mm (SD: 4.7 mm) for oscillating
      and continuous modes, respectively. Six EPL samples had a mean change in
      displacement of 4.7 (SD: 2.7 mm) and 4.3 mm (SD: 1.8 mm) for oscillating and
      continuous modes, respectively. CONCLUSIONS: Complete extensor tendon failure due
      to drill penetration was rare. Drill mode did not affect the degree of
      elongation. Increasing cyclic loading of extensor tendons after drill injury
      caused modest extensor tendon elongation.

PMID- 28453348
TI  - The Effect of Therapeutic Whirlpool and Hot Packs on Hand Volume During
      Rehabilitation After Distal Radius Fracture: A Blinded Randomized Controlled
      Trial.
AB  - BACKGROUND: Edema is a possibility with all heating modalities due to the
      increase in local blood flow caused by vasodilation. Despite the frequent
      application of superficial heat modalities, their relative effect on hand volume
      has not been determined for the upper extremity. The objective of this study was
      to compare the immediate effects of hot packs and whirlpool on hand volume for
      patients with distal radius fracture (DRF) and to determine whether any changes
      in volume between these modalities were still present 30 minutes after heat
      application. Finally, to determine whether there were any differences in volume
      change between groups after 3 repeated therapy visits. METHODS: Sixty patients
      with clinically healed DRFs were divided into 2 groups. Half received therapeutic
      whirlpool at each therapy visit, and the other half received a moist hot pack
      treatment for 3 consecutive visits. Hand volume was measured before heat, after
      heat, and at the end of each 30-minute therapy session. RESULTS: There was a
      significant difference between groups immediately after heat application, as
      patients in the whirlpool group experienced an initial volume increase greater
      than those who received a hot pack. When remeasured after a hand therapy session
      approximately 30 minutes later, this group difference in volume change was no
      longer significant. The overall change in volume from enrollment in the study to
      completion of the study 3 weeks later was not statistically different between
      groups. CONCLUSION: Whirlpool is a potential consideration when selecting a heat
      modality for patients with DRF.

PMID- 28453349
TI  - Chronic Exertional Compartment Syndrome of the Hand: Case Report and Literature
      Review.
AB  - BACKGROUND: Chronic exertional compartment syndrome (CECS) is characterized by
      activity-induced pain, swelling, and decreased muscle function due to increased
      pressure and decreased circulation within a confined muscle compartment. Although
      well-known to occur in the leg, involvement of the hand has rarely been reported
      in the literature. METHODS: We present a 44 year old male with CECS involving
      bilateral thenar and hypothenar compartments. Symptoms were reproduced on exam by
      driving screws into wood with a screwdriver. Elevated compartment pressures were
      confirmed with a hand-held digital device which employs a rigid needle that is
      readily directed to specific compartments. RESULTS: Selective releases of the
      thenar and hypothenar compartments were performed under local anesthesia and
      forearm tourniquet in the ambulatory surgery center. At 3-month follow-up, the
      patient reported full use of his right hand, including woodworking, with
      excellent relief of symptoms. At 5 months postoperatively, he underwent identical
      surgical releases on the contralateral left side, with similar relief.
      CONCLUSIONS: CECS of the hand is a rare condition. Our case is unique among prior
      reports with regard to pattern of compartment involvement, as well as provocative
      maneuvers and compartment testing methods employed. This report should help
      foster clinical suspicion, facilitate diagnosis, and demonstrate success of
      targeted surgical treatment.

PMID- 28453350
TI  - Prognostic Variables for Patient Return-to-Work Interval Following Carpal Tunnel
      Release in a Workers' Compensation Population.
AB  - BACKGROUND: We hypothesize that depressive and anxiety disorders, chronic pain
      conditions, and work-related factors are significant determinants of the time
      interval for return to work (RTW) in the workers' compensation (WC) population
      following carpal tunnel release (CTR) surgery. METHODS: We retrospectively
      reviewed records of all WC patients who underwent open CTR surgery over a 5-year
      period by 1 of 3 fellowship-trained hand surgeons. One hundred fifty-two wrists
      in 108 patients (64 unilateral, 44 bilateral) met the inclusion criteria.
      Demographic, medical, and surgical data were obtained from patient records.
      Bivariate and multivariate analyses were performed to assess predictors of RTW.
      RESULTS: Eighty-nine percent of all patients returned to work full-duty. Average
      RTW duration in all wrists was 12.5 +/- 11.3 weeks. Predictors of delayed RTW in
      bivariate and multivariate analyses were depression with or without anxiety,
      chronic pain disorders including fibromyalgia, preoperative opioid use, and
      modified preoperative work status. Job type, motor nerve conduction velocity, and
      bilateral surgery were not predictive of delayed RTW interval. CONCLUSIONS: WC
      patients with depression, anxiety, or fibromyalgia and other chronic pain
      disorders were significantly more likely to have delayed RTW following CTR than
      were WC patients without these conditions. In addition, those who use opioid
      medications preoperatively and those with preoperative work restrictions were
      also found to have a significantly delayed RTW after CTR. Knowledge of these risk
      factors may help care providers and employers identify those WC patients who are
      most likely to have a protracted postoperative recovery period.

PMID- 28453352
TI  - A Tribute to Jaiyoung Ryu, MD, From All of Us at the AAHS.

PMID- 28453351
TI  - Mallet Fractures of the Thumb Compared With Mallet Fractures of the Fingers.
AB  - BACKGROUND: The purpose of this study was to look for differences in mechanism,
      radiographic findings, and treatment between mallet fractures of the thumb and
      mallet fractures of the index through small fingers. METHODS: This retrospective
      study included 24 mallet fractures of the thumb and 392 mallet fractures of other
      digits. We compared demographics, injury factors (side, dominant hand, time
      between injury and first visit, and injury mechanism), subluxation, fragment
      size, treatment, and time from injury to final evaluation between the 2 groups.
      RESULTS: Mallet fractures of the thumb presented for treatment sooner after
      injury (2.9 vs 13 days on average), had less fragment displacement (27% vs 33%),
      and less articular involvement (39% vs 46% on average). None of the mallet
      fractures of the thumb had radiographic evidence of subluxation, whereas 25% of
      mallet fractures of other fingers had initial or later subluxation. CONCLUSIONS:
      Mallet fractures of the thumb are not likely to subluxate.

PMID- 28453353
TI  - HAND Has Been Accepted to MEDLINE!!

PMID- 28453354
TI  - Heterotopic Ossification After the Arthroscopic Treatment of Lateral
      Epicondylitis.
AB  - BACKGROUND: Heterotopic ossification (HO) is a well-known complication following
      the surgical treatment of fractures and dislocations about the elbow but it is
      not commonly discussed as a complication following arthroscopy. We present a case
      of a young athlete who developed HO after the arthroscopic treatment of lateral
      epicondylitis. METHODS: This is a case report chart review of a 24 year old male
      with lateral epicondylitis. After failing conservative measures, arthroscopic
      debridement of the extensor carpi radialis brevis (ECRB) origin ensued. The
      treatment and patient's final disposition were reported. RESULTS: The patient
      developed heterotopic ossification of the elbow follow arthroscopic debridement
      of the ECRB origin. Further surgery was required to excise the heterotopic
      ossification. Good recovery of motion was achieved. CONCLUSION: To our knowledge,
      we present the first case of HO development after elbow arthroscopy for lateral
      epicondylitis. As the use of elbow arthroscopy continues to grow, there is a need
      for identification of the risk factors and primary prophylaxis for HO.

PMID- 28453355
TI  - Open Versus Endoscopic Cubital Tunnel In Situ Decompression: A Systematic Review
      of Outcomes and Complications.
AB  - BACKGROUND: Endoscopic cubital tunnel release has been proposed as an alternative
      to open in situ release. However, it is difficult to analyze outcomes after
      endoscopic release, as only a few small case series exist. METHODS: The
      electronic databases of PubMed (1960-June 2014) were systematically screened for
      studies related to endoscopic cubital tunnel release or open in situ cubital
      tunnel release. Baseline characteristics, clinical scores, and complication rates
      were abstracted. The binary outcome was defined as rate of excellent/good
      response versus fair/poor. Complications were recorded into 3 categories: wound
      problems, persistent ulnar nerve symptoms, and other. RESULTS: We included 8
      articles that reported the clinical outcomes after surgical intervention
      including a total of 494 patients (344 endoscopic, 150 open in situ). The pooled
      rate of excellent/good was 92.0% (88.8%-95.2%) for endoscopic and 82.7% (76.15%
      89.2%) for open. We identified 18 articles that detailed complications including
      a total of 1108 patients (691 endoscopic, 417 open). The 4 articles that listed
      complication rates for both endoscopic and open techniques were analyzed and
      showed a pooled odds ratio of 0.280 (95% confidence interval, 0.125-0.625),
      indicating that endoscopic patients have reduced odds of complications.
      CONCLUSIONS: The results of this systematic review suggest that there is a
      difference in clinical outcomes between the open in situ and endoscopic cubital
      tunnel release, with the endoscopic technique being superior in regard to both
      complication rates along with patient satisfaction.

PMID- 28453356
TI  - Improved Surgical Outcomes With Endoscopic Carpal Tunnel Release in Patients With
      Severe Median Neuropathy.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) can be treated with open carpal tunnel
      release (OCTR) or endoscopic carpal tunnel release (ECTR). Our goal was to
      evaluate the safety and efficacy of ECTR versus OCTR in patients with severe CTS.
      We hypothesized that ECTR would be as safe and effective as OCTR in these
      patients. METHODS: This was a retrospective cohort study of patients with severe
      CTS who underwent ECTR or OCTR by E. G. Deune between 2001 and 2014. Variables
      were patient age, sex, relevant medical history, alcohol and tobacco use, and
      preoperative electromyography and physical examination results. The primary
      outcome was patient-reported resolution of neuropathic symptoms at last follow
      up. Secondary outcomes were surgical complications and need for reoperation. We
      compared the cohorts using Student's t tests and chi-square tests. RESULTS: We
      identified 138 cases of severe CTS in 126 patients who met our inclusion
      criteria. Thirty-nine cases were treated with ECTR and 99 with OCTR. Mean ages
      were 59 years (ECTR group) and 56 years (OCTR group). The population was 68%
      women, and 56% of cases involved the dominant hand. The distributions of age,
      sex, hand dominance, presence of relevant medical history, and alcohol and
      tobacco use did not differ significantly between groups. Treatment completely
      resolved CTS symptoms in 82% of ECTR cases and 39% of OCTR cases. Complication
      rates (all causes) were similar for both procedures. Recurrence was observed in
      2.6% of ECTR cases and 10% of OCTR cases. CONCLUSIONS: ECTR is a safe and
      effective alternative to OCTR for patients with severe CTS.

PMID- 28453357
TI  - The Diagnosis and Management of Mallet Finger Injuries.
AB  - BACKGROUND: Mallet finger is a common injury of the extensor tendon insertion
      causing an extension lag of the distal interphalangeal joint. METHODS: We
      reviewed the most current literature on the epidemiology, diagnosis, and
      management of mallet finger injuries focusing on the indications and outcomes of
      surgical intervention. RESULTS: Nonoperative management has been advocated for
      almost all mallet finger injuries; however, complex injuries are usually treated
      surgically. There is still controversy regarding the absolute indications for
      surgical intervention. CONCLUSIONS: Although surgery is generally indicated in
      the case of mallet fractures involving more than one-third of the articular
      surface as well as in all patients who develop volar subluxation of the distal
      phalanx, a significant advantage of surgical management even in those complicated
      cases has yet to be clearly proven.

PMID- 28453358
TI  - Bereavement Service Preferences of Surviving Family Members: Variation among Next
      of Kin with Depression and Complicated Grief.
AB  - BACKGROUND: Research indicates that bereavement services reduce distress and
      support adjustment in the bereaved, particularly those experiencing significant
      levels of depression or grief. However, the service use of bereaved individuals
      and whether utilization differs among those experiencing depression and
      complicated grief currently remain unclear. Research is needed to clarify the
      preferences of the bereaved, including specific bereaved subgroups. OBJECTIVES:
      The purpose of this study was to explore the bereavement service preferences of
      bereaved family members whose loved one died in the hospital and identify group
      differences in service use among individuals with and without depression and
      complicated grief, considering time since the death of the patient. DESIGN: In
      this cross-sectional study, self-report data were collected from family members
      primarily between 3 and 18 months following the death of the patient in the
      hospital. SETTING: Academic medical center. MEASUREMENTS: We explored helpfulness
      ratings and actual and projected service utilization of a comprehensive list of
      hospital and community bereavement services, and compared findings between those
      with and without depression and complicated grief, considering timing since
      patient death. RESULTS: Services receiving the highest helpfulness ratings by the
      entire sample included time alone with the deceased, a quiet room to be alone
      after the death, sympathy cards from hospital staff, memorial services, chaplain
      support before/during time of death, an educational grief booklet, grief book
      recommendations, a check-in phone call from hospital staff, individual
      counseling, and a relationship-specific support group. Individuals with
      depression and complicated grief reported a greater willingness to utilize
      specific services, including a memorial website, support groups, a holiday
      workshop, and individual/family psychotherapy. CONCLUSION: Findings indicate a
      difference in the projected service use of the bereaved experiencing depression
      and/or complicated grief. Follow-up screenings 6-12 months post-bereavement are
      recommended to identify those in need of formal psychosocial support.

PMID- 28453359
TI  - Commentary on Costa et al.: "Influence of Ambient Temperature and Confinement on
      the Chemical Immobilization of Fallow Deer ( Dama dama )".

PMID- 28453360
TI  - Reply to Arnemo and Kreeger: "Commentary on 'Influence of Ambient Temperature and
      Confinement on the Chemical Immobilization of Fallow Deer ( Dama dama )'".

PMID- 28453361
TI  - Trends in Hospital Utilization and Costs among Pediatric Palliative Care
      Recipients.
AB  - OBJECTIVE AND BACKGROUND: Few previous studies have explored how pediatric
      palliative care (PPC) influences hospital utilization. We evaluated this among
      PPC recipients in a single center. METHODS: This is a retrospective cohort study
      of 109 patients >=2 years of age who received PPC consultation at a large
      quaternary children's hospital from April 2009 to September 2010. We assessed
      frequencies of hospital admissions and emergency department (ED) visits, use of
      intensive interventions, and hospital costs. Generalized estimating equations
      were used to compare outcomes in the two years before and after PPC consultation,
      stratifying by whether a patient survived two or more years following PPC
      enrollment. RESULTS: Median age at PPC consultation was 13 years (interquartile
      range 6-18); 56.0% were male (n = 61), 69.7% white non-Hispanic (n = 76). Fifty
      nine percent (n = 64) of patients died during the study period. Overall, annual
      hospital admission rates decreased from 4.6 (95% confidence interval [CI] 4.0
      5.4) before PPC consultation to 3.7 (95% CI 3.4-4.4) after (p = 0.025). Annual ED
      visits decreased from 0.9 (95% CI 0.7-1.2) to 0.6 (95% CI 0.4-0.8) (p = 0.030).
      Survivors had significantly decreased hospital admissions [rate ratio (RR) 0.57
      (95% CI 0.45-0.73), p < 0.001] and ED visits [RR 0.33 (95% CI 0.20-0.54), p <
      0.001]. Decedents had increased intensive care unit use (p = 0.029) but decreased
      operations (p = 0.002); survivors experienced no change in these outcomes after
      PPC consultation. Hospital costs remained stable for all (p = 0.929). DISCUSSION:
      PPC involvement may contribute to decreased hospital and ED use, without
      escalating costs. These outcomes are most evident in survivors. Hence, PPC may
      have a measurable long-term impact on hospital use in seriously ill children.

PMID- 28453362
TI  - A novel mutation in the dominantly inherited TOPORS gene supports
      haploinsufficiency as the mechanism of retinitis pigmentosa.
AB  - BACKGROUND: Inherited retinal degenerations are a major cause of untreatable
      blindness in the younger age group. Recent advances in gene therapy using adeno
      associated viral (AAV) vectors have raised the possibility of slowing or stopping
      retinal degenerations with gene replacement in cases of gene deficiency.
      MATERIALS AND METHODS: In this report, we present a family with autosomal
      dominant retinitis pigmentosa. A screen for common ADRP genes was performed with
      105 genes targeted. Next generation sequencing was used to identify the mutation
      which was next confirmed by bidirectional Sanger sequencing. RESULTS: A novel
      mutation of the TOPORS gene was identified, c.2539C>T p.(Arg847Ter), resulting in
      a premature termination codon and suggesting haploinsufficiency as the
      pathological mechanism. CONCLUSIONS: Since the cDNA encoding TOPORS is 3,135
      nucleotides (within the coding capacity of AAV vectors) and haploinsufficiency is
      a mechanism relating to inadequate gene expression, gene replacement therapy may
      be an option for patients with this condition.

PMID- 28453363
TI  - A Polyphenol-Based Multicomponent Nutraceutical in Dysmetabolism and Oxidative
      Stress: Results from a Pilot Study.
AB  - To assess short-term efficacy and safety of a multicomponent nutraceutical (MCN)
      on dysmetabolism and oxidative stress, a pilot prospective observational study
      was performed on 21 individuals (12 men and 9 women) who took, for 60 days, 2
      tablets per day of an MCN based on antioxidants and metabolism regulators:
      hydroxytyrosol (15 mg), maqui (300 mg), amla (200 mg), monacolin K (10 mg),
      berberine (245 mg), astaxanthin (0.5 mg), coenzyme Q10 (100 mg), and folic acid
      (200 mcg). On day 0 (T0) and day 60 (T60), all participants underwent laboratory
      tests related to lipid profile, carbohydrate metabolism, oxidative stress, and
      cellular inflammation. Statistical analysis was applied to the resulting data. A
      significant improvement of most atherogenesis and oxidative stress biomarkers was
      recorded (mean figure at T0 and T60, p value): total cholesterol 243.50/194.83
      mg/dl, p =.0002; low-density lipoproteins 174.50/124.58 mg/dl, p =.0001; glycemia
      96.25/88.50 mg/dl, p =.035; total free radicals 306.44/280.93 U.Carr., p =.036;
      serum antioxidant capacity 2103.00/2246.06 umol/l, p =.0042; oxidized cholesterol
      680.33/597.25 uEq/l, p =.0511. Insulinemia, microalbuminuria, high-density
      lipoproteins, C-reactive protein, and triglycerides had no statistically
      significant variation. Body weight and systo-diastolic pressure showed no
      significant change from T0 to T60. No relevant side effects were reported. The
      investigated MCN (Eonlipid), based on polyphenols, significantly improved the
      oxidative stress parameters and decreased the majority of atherogenesis
      parameters at short term. No significant side effects were reported. Further
      placebo-controlled studies should possibly corroborate the promising results of
      this pilot study.

PMID- 28453364
TI  - Quantification of UCP1 function in human brown adipose tissue.
AB  - Brown adipose tissue (BAT) mitochondria are distinct from their counterparts in
      other tissues in that ATP production is not their primary physiologic role. BAT
      mitochondria are equipped with a specialized protein known as uncoupling protein
      1 (UCP1). UCP1 short-circuits the electron transport chain, allowing
      mitochondrial membrane potential to be transduced to heat, making BAT a tissue
      capable of altering energy expenditure and fuel metabolism in mammals without
      increasing physical activity. The recent discovery that adult humans have
      metabolically active BAT has rekindled an interest in this intriguing tissue,
      with the overarching aim of manipulating BAT function to augment energy
      expenditure as a countermeasure for obesity and the metabolic abnormalities it
      incurs. Subsequently, there has been heightened interest in quantifying BAT
      function and more specifically, determining UCP1-mediated thermogenesis in BAT
      specimens - including in those obtained from humans. In this article, BAT
      mitochondrial bioenergetics will be described and compared with more conventional
      mitochondria in other tissues. The biochemical methods typically used to quantify
      BAT mitochondrial function will also be discussed in terms of their specificity
      for assaying UCP1 mediated thermogenesis. Finally, recent data concerning BAT
      UCP1 function in humans will be described and discussed.

PMID- 28453365
TI  - A novel method for designing and optimizing the layout of facilities in bathroom
      for the elderly in home-based rehabilitation.
AB  - PURPOSE: The home-based rehabilitation of elderly patients improves their
      autonomy, independence and reintegration into society. Hence, a suitable
      environment plays an important role in rehabilitation, as do different assistance
      technologies. The majority of accidents at home involving elderly people occur in
      the bathroom. Therefore, the planning of the layout of facilities is important in
      this potentially dangerous area. This paper proposes an approach towards
      designing and optimizing the layout of facilities in the bathroom, based on
      logistical and nonlogistical relationships. METHODOLOGY: A fuzzy-based analytical
      hierarchical process (fuzzy-AHP) is then proposed for a comprehensive evaluation
      of the alternatives for this layout plan. This approach was applied to the home
      of a 71 years old female patient, who was experiencing home-based rehabilitation.
      After the initial designing and optimizing of the layout of the facilities in her
      bathroom, a plan could then be created for her particular needs. FINDINGS: The
      results of this research could then enable the home-based rehabilitation of
      elderly patients to be more effective. Value: This paper develops a new approach
      to design and optimize the layout of facilities in bathroom for the elderly.
      Implications for Rehabilitation Develop a new approach to design and optimize the
      layout of facilities in bathroom. Provide a mathematical and more scientific
      approach to home layout design for home-based rehabilitation. Provide new
      opportunities for research, for both the therapist and the patient to analyse the
      home facility layout.

PMID- 28453366
TI  - Patterns of visual field changes in thyroid eye disease.
AB  - This article provides a systematic description of visual field changes in thyroid
      eye disease-compressive optic neuropathy (TED-CON). A retrospective, non
      comparative chart review of patients with TED-CON and documented Humphrey Visual
      Field 24-2 or 30-2 testing was conducted with IRB approval. Ninety-six visual
      fields in 68 patients were classified into 7 broad categories (superior,
      inferior, diffuse, temporal, nasal, central/paracentral, enlarged blind spot) and
      17 mutually exclusive patterns from the Ocular Hypertension Treatment Study
      (OHTS) or "other." Fifty-three of 96 visual fields (55%) showed an inferior
      defect using the broad categories, with the remaining 6 categories ranging from
      2% to 14%. The five most common OHTS patterns were other (28%), partial arcuate
      (28%), partial peripheral rim (9%), arcuate (8%) and altitudinal (7%). Further
      sub-classification showed a predominance of inferior visual field defects,
      ranging from 33% to 93% of each category. Of the 78 visual fields in these five
      categories combined, 52 (67%) were inferior defects. Inferior defect is the most
      typical TED-CON-associated visual field change. While the OHTS categories are
      geared toward classification of glaucomatous patterns, the overall predominance
      of inferior field defects in TED-CON was clearly demonstrated. These "other"
      visual field changes showing central inferior defect up to but not crossing the
      horizontal meridian and not contiguous from blind spot to nasal meridian should
      be designated as "TED-CON pattern." The high proportion of visual fields falling
      under the "other" category, however, does demonstrate the need for a more
      specific and tailored visual field classification system for TED-CON.

PMID- 28453367
TI  - Retinal pigment epithelium-photoreceptor layer alterations in a patient with
      Sturge-Weber syndrome with diffuse choroidal hemangioma.
AB  - PURPOSE: To describe an 8-year-old girl with diagnosis of Sturge-Weber syndrome
      (SWS) presenting with glaucoma, abnormal iris vessels, diffuse choroidal
      hemangioma, and small white dot-shaped "microdrusen-like" alterations of the
      retina in the right eye. PATIENT AND METHODS: Complete ophthalmological
      examination was performed with slit-lamp anterior segment assessment and fundus
      ophthalmoscopy. Near infrared reflectance (NIR) and enhanced depth imaging (EDI)
      spectral domain optical coherence tomography (SD-OCT) were carried out. RESULTS:
      Microdrusen-like retinal alterations observed with fundus ophthalmoscopy appeared
      as multiple hyperreflective dots surrounded by a hyporeflective ring on NIR. EDI
      SD-OCT showed increased choroidal thickness exceeding 1000 MUm. B-scan cross
      sectional examination on the hyperreflective dots revealed focal alterations of
      the retinal pigment epithelial (RPE)-photoreceptor layer. CONCLUSIONS: The
      increase of the choroidal thickness due to the diffuse choroidal hemangioma
      caused alterations of the RPE-photoreceptor layer similar to reticular
      pseudodrusen or pachychoroid pigment epitheliopathy.

PMID- 28453368
TI  - Establishment of expanded and streamlined pipeline of PITCh knock-in - a web
      based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the
      variations of PITCh, PITCh-TG and PITCh-KIKO.
AB  - The emerging genome editing technology has enabled the creation of gene knock-in
      cells easily, efficiently, and rapidly, which has dramatically accelerated
      research in the field of mammalian functional genomics, including in humans. We
      recently developed a microhomology-mediated end-joining-based gene knock-in
      method, termed the PITCh system, and presented various examples of its
      application. Since the PITCh system only requires very short microhomologies (up
      to 40 bp) and single-guide RNA target sites on the donor vector, the targeting
      construct can be rapidly prepared compared with the conventional targeting vector
      for homologous recombination-based knock-in. Here, we established a streamlined
      pipeline to design and perform PITCh knock-in to further expand the availability
      of this method by creating web-based design software, PITCh designer (
      http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html ), as well as
      presenting an experimental example of versatile gene cassette knock-in. PITCh
      designer can automatically design not only the appropriate microhomologies but
      also the primers to construct locus-specific donor vectors for PITCh knock-in. By
      using our newly established pipeline, a reporter cell line for monitoring
      endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO)
      cell line can be produced systematically. Using these new variations of PITCh, an
      exogenous promoter-driven gene cassette expressing fluorescent protein gene and
      drug resistance gene can be integrated into a safe harbor or a specific gene
      locus to create transgenic reporter cells (PITCh-TG) or knockout cells with
      reporter knock-in (PITCh-KIKO), respectively.

PMID- 28453369
TI  - Inhibition of Inflammatory Response by Crocin Attenuates Hemorrhagic Shock
      Induced Organ Damages in Rats.
AB  - Hemorrhagic shock (HS) is associated with an excessive activation of
      inflammation, contributing to multiple organ failure in numerous medical or
      surgical conditions. To explore the therapeutic potential of crocin, a natural
      compound with anti-inflammatory properties, we administered crocin to rats during
      resuscitation following HS induced by withdrawing blood. Compared with control
      animals which were sham-treated, HS-operated rats showed organ damages as
      manifested by enhanced markers of multiple organ dysfunctions. Crocin treatment
      substantially reduced these parameters in rats subjected to HS, suggesting an
      alleviation of tissue injuries such as in the kidney, liver, pancreas, and
      muscle. The activation of NF-kappaB (nuclear factor kappaB) pathway in lung
      tissue by HS, as shown by increased nuclear translocation of p65 and IkappaBalpha
      phosphorylation, was diminished by crocin treatment. The crocin administration
      also significantly decreased the serum levels of proinflammatory cytokine TNF
      alpha (tumor necrosis factor-alpha) and interleukin (IL)-6, whereas increased the
      level of anti-inflammatory cytokine IL-10 in HS-operated rats. These studies
      indicate that crocin administration may reduce inflammation-driven tissue damage
      in patients with HS.

PMID- 28453370
TI  - School absence and productivity outcomes associated with childhood asthma in the
      USA.
AB  - BACKGROUND: Previous studies have examined the association between childhood
      asthma and lost productivity; however, more data are needed to understand its
      impact. METHODS: This was a retrospective analysis of cross-sectional data in the
      nationally representative 2007-2013 Medical Expenditure Panel Survey (MEPS).
      School-aged children (SAC), children (age 6-11), and adolescents (age 12-17) with
      asthma were compared to those without asthma to examine annual missed school
      days. Adult parents/caregivers of SAC with asthma were compared to those of SAC
      without asthma to examine missed work days. The cost of premature asthma
      mortality for SAC was also estimated. Negative binomial regression was used for
      missed school days, and a two-part model structure was used for missed work days.
      All analyses controlled for sociodemographics and other covariates. RESULTS:
      There were 44,320 SAC of whom 5,890 had asthma. There were 43,496 employed adults
      with at least one child. SAC (6-17) with asthma missed 1.54 times the number of
      school days compared to SAC without asthma. Caregivers of SAC (6-17) with asthma
      missed 1.16 times the number of work days to care for others compared to
      caregivers of SAC without asthma. SAC in the USA missed an additional 7 million
      school days associated with asthma (3.7 million children and 3.3 million
      adolescent). There were 130 asthma deaths resulting in an annual cost of $211
      million ($US 2015). CONCLUSIONS: Childhood asthma is associated with a
      significant school absence and productivity loss in the USA. Better treatment and
      asthma management programs are needed to alleviate this burden.

PMID- 28453371
TI  - Megalocornea associated with microduplications on chromosome 16.

PMID- 28453373
TI  - Are We Making Progress?

PMID- 28453372
TI  - Renal Tubular Mitochondrial Abnormalities in Complex II/III Respiratory Chain
      Deficiency.
AB  - Defects in the respiratory chain may present with a wide spectrum of clinical
      signs and symptoms. In this "Images in Pathology" discussion we correlate the
      clinical, histologic, and ultrastructural findings in a 12-year-old male with a
      complex II/III respiratory chain deficiency and kidney dysfunction.

PMID- 28453374
TI  - Intraocular Cytokine Levels in Post-Cataract Endophthalmitis and their
      Association with Visual Outcome.
AB  - PURPOSE: The host immune reaction during endophthalmitis, studied in particular
      through the intraocular cytokine network, is essential for the comprehension of
      the disease and the development of new therapies. Therefore, the purpose of this
      study was to elucidate the cytokine composition of aqueous humor during
      endophthalmitis. METHODS: In a multicenter case-control study, forty-nine
      patients with postoperative endophthalmitis and 60 controls (cataract surgery)
      were included. Visual acuity, local inflammatory grading, medical history and
      intraocular levels of 27 cytokines and chemokines (measured by multiplex
      immunoassay) were recorded. RESULTS: During endophtalmitis, an increase in total
      cytokines was observed. The raise of Th1 cytokines was particularly noticeable.
      Chemokines, such as IL-8, MIP-1 beta, MCP-1, G-CSF and IP-10, also increased.
      Pearson's correlation analyses showed a poor visual prognosis with high levels of
      IL-8, MCP-1 and VEGF and a low level of IL-10 at admission. CONCLUSION: An
      increase in inflammatory cytokines is noticeable during endophthalmitis, with a
      particular emphasis on IL-8, MCP-1 and VEGF. Targeted anti-inflammatory and anti
      VEGF treatments may be of interest in the future.

PMID- 28453375
TI  - Genetic factors influencing the reduction of central corneal thickness in
      disorders affecting the eye.
AB  - BACKGROUND: The aim was to summarize and discuss the current knowledge about
      genetic factors influencing the reduction of central corneal thickness (CCT) in
      disorders affecting the eye, such as primary open-angle glaucoma (POAG), brittle
      cornea syndrome (BCS), keratoconus (KTCN), Ehlers-Danlos syndrome (EDS; types I,
      II, and VI), osteogenesis imperfecta (OI), and myopia. MATERIALS AND METHODS: A
      review of the published literature by use of key databases such as PubMed was
      undertaken in accordance with PRISMA guidelines and experience based on own
      research findings was applied. RESULTS: The differences in CCT measurements among
      those affected with diverse disorders and healthy individuals were evaluated.
      Then we considered the influence of genetic factors on CCT reduction. Disorders
      were compared based on phenotypes and sequence variants found in patients.
      CONCLUSIONS: Specific sequence variants in COL8A2, PRDM5 and ZNF469, COL5A1 and
      ZNF469, and COL5A1 and COL5A2 could probably contribute to a CCT reduction in
      POAG, BCS, KTCN, and EDS, respectively. Similar sequence variants and phenotypes
      were identified and assessed in more than one disease.

PMID- 28453376
TI  - Control of the Unfolded Protein Response in Health and Disease.
AB  - The unfolded protein response (UPR) is an integrated, adaptive biochemical
      process that is inextricably linked with cell homeostasis and paramount to
      maintenance of normal physiological function. Prolonged accumulation of
      improperly folded proteins in the endoplasmic reticulum (ER) leads to stress.
      This is the driving stimulus behind the UPR. As such, prolonged ER stress can
      push the UPR past beneficial functions such as reduced protein production and
      increased folding and clearance to apoptotic signaling. The UPR is thus
      contributory to the commencement, maintenance, and exacerbation of a multitude of
      disease states, making it an attractive global target to tackle conditions sorely
      in need of novel therapeutic intervention. The accumulation of information of
      screening tools, readily available therapies, and potential pathways to drug
      development is the cornerstone of informed clinical research and clinical trial
      design. Here, we review the UPR's involvement in health and disease and, beyond
      providing an in-depth description of the molecules found to target the three UPR
      arms, we compile all the tools available to screen for and develop novel
      therapeutic agents that modulate the UPR with the scope of future disease
      intervention.

PMID- 28453377
TI  - Investigation of the relationship between asthma and subclinical atherosclerosis
      by carotid/femoral intima media and epicardial fat thickness measurement.
AB  - OBJECTIVE: Since asthma and atherosclerosis may share similar pathophysiological
      mechanism, this study is planned to investigate whether epicardial fat thickness
      (EFT), carotid and femoral intima media thicknesses, which are markers of
      subclinical atherosclerosis, are increased in patients with asthma. METHODS: The
      study was designed as a cross-sectional study. A total of 154 participants (83
      patients with asthma and 71 healthy volunteers) were enrolled into the study.
      Epicardial fat, carotid, and femoral intima media thicknesses were measured and
      recorded in both groups. The statistical difference between the two groups was
      examined. RESULTS: Both carotid and femoral intima media thicknesses were
      significantly higher in patients with asthma compared to control group (5.52 +/-
      0.4 mm vs. 5.36 +/- 0.4 mm; p = 0.038 and 5.64 +/- 0.4 mm vs. 5.46 +/- 0.5 mm; p
      = 0.036, respectively). However, there was not a significant difference in EFT
      between the groups [5.9 mm (5.3-6.6; IQR = 1.3) vs. 5.6 mm (4.7-6.5; IQR = 1.8);
      p = 0.1]. On comparison of control group and asthma subgroups (mild, moderate,
      and severe), there was a statistically significant difference among these four
      groups in terms of carotid and femoral intima media thicknesses (p = 0.002 and p
      < 0.001, respectively). Subgroup analyses showed that this difference was mainly
      due to patients with severe asthma. CONCLUSIONS: Carotid and femoral intima media
      thicknesses in asthmatic patients were found to be increased compared to the
      normal population. As a result, the risk of subclinical atherosclerosis in
      asthmatic patients may be high.

PMID- 28453378
TI  - Effectiveness of written action plans for acute asthma: A systematic review.
AB  - OBJECTIVE: Self-management is an essential part of achieving asthma control and
      improving long-term outcomes. While guidelines recommend the provision of written
      asthma action plans (AAPs), few patients presenting to emergency departments (ED)
      have one. This systematic review examined if individualized written AAPs reduce
      relapses in adults following an ED visit for acute asthma. DATA SOURCES:
      Comprehensive searches of seven electronic databases and grey literature were
      conducted. STUDY SELECTIONS: Randomized controlled trials (RCTs) examining the
      effectiveness of individualized written AAPs to reduce relapses after ED visits
      for acute asthma were included. Study quality was determined using the Cochrane
      Risk of Bias (RoB) tool; intervention fidelity was assessed. RESULTS: From 695
      potentially relevant studies, three RCTs were included. The RoB was low in two
      studies and high in one study; description of intervention fidelity varied across
      studies. The provision of individualized written AAPs in adults following an ED
      visit for acute asthma did not reduce the risk of relapse after ED discharge
      (risk ratio [RR] = 0.66; 95% confidence intervals [CI]: 0.36, 1.23; I2 = 40%).
      There was a 49% reduction in the risk of relapse after ED discharge when only
      studies with low RoB were pooled (RR = 0.51; 95% CI: 0.31, 0.83; I2 = 0%).
      CONCLUSION: This review did not provide conclusive evidence to support the
      consideration of individualized written AAPs for the reduction of relapses after
      an ED visit; however, the low frequency of events, small number of studies and
      samples, and their methodological quality might play an important role in this
      overall finding.

PMID- 28453379
TI  - Pseudoamniotic Band Syndrome Post Fetal Thoracoamniotic Shunting for Bilateral
      Hydrothorax.
AB  - INTRODUCTION: Pseudoamniotic band syndrome (PABS) occurs iatrogenically after
      fetal surgery or amniocentesis due to chorioamniotic membrane separation.
      Separation of the amnion from the chorion can expand to form fibrous amniotic
      bands that can envelope fetal limbs or the umbilical cord, with consequences
      ranging from limb constriction to fetal demise. CASE REPORT: We report a case of
      bilateral fetal pleural effusions at 27 weeks' gestation treated by bilateral
      thoracoamniotic shunts. Following shunt placement, the hydrothorax resolved.
      However, chorioamniotic membrane separation developed resulting in PABS with
      subsequent umbilical cord strangulation and fetal demise at 32 weeks' gestation.
      CONCLUSION: PABS has been previously described in the literature following
      various fetal interventions. This is the first reported case of pseudoamniotic
      band syndrome after placement of fetal thoracoamniotic shunts. A high index of
      suspicion is required to diagnose PABS via postoperative ultrasound. Post
      intervention chorioamniotic membrane separation warrants close surveillance for
      sonographic evidence of PABS.

PMID- 28453380
TI  - Lipids on the Second Day in Ischemic and Normoxemic Term Neonates.
AB  - INTRODUCTION: In hypoxic newborns requiring oxygen, lipid peroxidation affects
      the peripheral blood lipids. OBJECTIVES: Determine the influence of perinatal
      oxygen therapy for hypoxia on serum lipid concentrations on the second day of
      life. MATERIALS AND METHODS: Our study included 50 newborns with perinatal
      hypoxia requiring oxygen and 50 healthy newborns without oxygen therapy.
      Arterialized capillary blood was taken for categorization of hypoxia (pO2) after
      birth in both groups. Lipid concentrations: total cholesterol (TC), high density
      lipoproteins (HDL), low density lipoproteins (LDL), and triglycerides (TG) were
      measured on day 2 in both groups. RESULTS: TC, LDL, HDL, TG, HC03 levels were
      statistically lower in the study group compared to the control one, while pCO2
      and BE levels were statistically higher in newborns with perinatal hypoxia.
      CONCLUSION: Lower lipid levels in hypoxic newborns may suggest that circulating
      lipids are oxidized, peroxidized, and removed from the peripheral circulation.

PMID- 28453383
TI  - Applications of Platelet-Rich Plasma in Lymphedema.

PMID- 28453382
TI  - Flow cytometric single cell analysis reveals heterogeneity between adipose
      depots.
AB  - Understanding adipose tissue heterogeneity is hindered by the paucity of methods
      to analyze mature adipocytes at the single cell level. Here, we report a system
      for analyzing live adipocytes from different adipose depots in the adult mouse.
      Single cell suspensions of buoyant adipocytes were separated from the stromal
      vascular fraction and analyzed by flow cytometry. Compared to other lipophilic
      dyes, Nile Red uptake effectively distinguished adipocyte populations. Nile Red
      fluorescence increased with adipocyte size and granularity and could be combined
      with MitoTracker(r) Deep Red or fluorescent antibody labeling to further dissect
      adipose populations. Epicardial adipocytes exhibited the least mitochondrial
      membrane depolarization and highest fatty-acid translocase CD36 surface
      expression. In contrast, brown adipocytes showed low surface CD36 expression.
      Pregnancy resulted in reduced mitochondrial membrane depolarisation and increased
      CD36 surface expression in brown and epicardial adipocyte populations
      respectively. Our protocol revealed unreported heterogeneity between adipose
      depots and highlights the utility of flow cytometry for screening adipocytes at
      the single cell level.

PMID- 28453381
TI  - Degradation of protein translation machinery by amino acid starvation-induced
      macroautophagy.
AB  - Macroautophagy is regarded as a nonspecific bulk degradation process of
      cytoplasmic material within the lysosome. However, the process has mainly been
      studied by nonspecific bulk degradation assays using radiolabeling. In the
      present study we monitor protein turnover and degradation by global, unbiased
      approaches relying on quantitative mass spectrometry-based proteomics.
      Macroautophagy is induced by rapamycin treatment, and by amino acid and glucose
      starvation in differentially, metabolically labeled cells. Protein dynamics are
      linked to image-based models of autophagosome turnover. Depending on the inducing
      stimulus, protein as well as organelle turnover differ. Amino acid starvation
      induced macroautophagy leads to selective degradation of proteins important for
      protein translation. Thus, protein dynamics reflect cellular conditions in the
      respective treatment indicating stimulus-specific pathways in stress-induced
      macroautophagy.

PMID- 28453384
TI  - Isolation and characterization of Ulva prolifera actin1 gene and function
      verification of the 5' flanking region as a strong promoter.
AB  - Ulva prolifera is a green macroalgae with an extremely high growth rate that can
      accumulate biomass with considerable protein content. To set up an available
      seaweed expression system, a prior step is to isolate endogenous and strong
      constitutive promoters. For this reason, the full-length genomic actin1 gene from
      U. prolifera (Upactin1) was cloned and its 5' flanking sequence was obtained by
      genome walking. The Upactin1 open reading frame consisted of 1134 nucleotides
      encoding 377 amino acid residues. Besides 4 exons and 3 introns in the coding
      region, an extra leader intron was identified in the 5' untranslated region.
      According to quantitative GUS assays based on transient expression, the promoter
      activity of the Upactin1 5' flanking region was found to be several times higher
      than that of the widely-used cauliflower mosaic virus 35S (CaMV35S) in all tested
      species of Ulva. In addition, precise deletion of the leader intron led to a
      significant decrease of promoter strength in U. prolifera, and almost entire loss
      of strength in U. linza and U. pertusa. To our knowledge, this is the first
      report to prove function of a leader intron in algae. The 5' flanking region of
      Upactin1 was shown to be a much stronger promoter than the foreign CaMV35S, and
      its activity was highly dependent on the presence of the leader intron. We
      propose that the Upactin1 promoter could serve as an endogenous and strong
      constitutive element for genetic engineering of U. prolifera.

PMID- 28453385
TI  - Performance improvement of microbial fuel cell (MFC) using suitable electrode and
      Bioengineered organisms: A review.
AB  - There is an urgent need to find an environment friendly and sustainable
      technology for alternative energy due to rapid depletion of fossil fuel and
      industrialization. Microbial Fuel Cells (MFCs) have operational and functional
      advantages over the current technologies for energy generation from organic
      matter as it directly converts electricity from substrate at ambient temperature.
      However, MFCs are still unsuitable for high energy demands due to practical
      limitations. The overall performance of an MFC depends on microorganism,
      appropriate electrode materials, suitable MFC designs, and optimizing process
      parameters which would accelerate commercialization of this technology in near
      future. In this review, we put forth the recent developments on microorganism and
      electrode material that are critical for the generation of bioelectricity
      generation. This would give a comprehensive insight into the characteristics,
      options, modifications, and evaluations of these parameters and their effects on
      process development of MFCs.

PMID- 28453386
TI  - Collateral damage during antibiotic treatment of C. difficile infection in the
      aged host: Insights into why recurrent disease happens.
AB  - Clostridium difficile infection (CDI) is one of the most common causes of
      healthcare-associated infections but an even bigger problem for the aging
      population. Advanced age leads to higher incidence, higher mortality, and higher
      recurrences. In our study, recently published in the Journal of Infectious
      Diseases, we investigated the effect of aging on CDI using a mouse model. We were
      able to demonstrate that aging leads to worse clinical outcomes, as well as lead
      to changes in microbiota composition and lower antibody production against C.
      difficile toxin A, but not toxin B. An association between advanced age and lower
      antibody production against C. difficile is a new finding which would explain the
      effect of aging on CDI outcome. Vancomycin, an anti-C. difficile antibiotic, led
      to similar changes in antibody response, suggesting a connection between
      microbiome and antibody response in the context of aging, which would require a
      much more nuanced look at the treatment of CDI.

PMID- 28453387
TI  - If They Don't Count Us, We Don't Count: Trump Administration Rolls Back Sexual
      Orientation and Gender Identity Data Collection.
AB  - The Trump Administration recently removed sexual orientation and gender identity
      (SOGI) questions from a national aging survey, and decided not to add a sexual
      orientation category and a transgender identity field to a national disability
      survey as planned. These actions have raised concerns that the major expansion of
      SOGI data collection on surveys and in clinical settings, which has occurred in
      recent years, may be under threat. SOGI data collection is essential to
      understand lesbian, gay, bisexual, and transgender (LGBT) health and the extent
      to which LGBT people access critical social services, including elder and
      disability services essential for living in community.

PMID- 28453388
TI  - Susceptibility of ATM-deficient pancreatic cancer cells to radiation.
AB  - Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of
      pancreatic ductal adenocarcinomas and may be predictor of treatment response. We
      determined if ATM deficiency renders pancreatic cancer cells more sensitive to
      fractionated radiation or commonly used chemotherapeutics. ATM expression was
      knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA.
      Isogenic cell lines were tested for sensitivity to several chemotherapeutic
      agents and radiation. DNA repair kinetics were analyzed in irradiated cells using
      the comet assay. We find that while rendering pancreatic cancer cells ATM
      deficient did not significantly change their sensitivity to several
      chemotherapeutics, it did render them exquisitely sensitized to radiation.
      Pancreatic cancer ATM status may help predict response to radiotherapy.

PMID- 28453389
TI  - GWAS analysis of treatment resistant schizophrenia: interaction effect of
      childhood trauma.
AB  - AIMS: In the current study, we aimed to compare the prevalence of adverse
      lifetime events in treatment resistant and non-treatment resistant schizophrenia
      in a genome-wide association study. MATERIALS & METHODS: Our sample consisted of
      84 Caucasian participants with schizophrenia spectrum disorders, assessed cross
      sectionally to collect information regarding drug effectiveness and childhood
      trauma. Using a genome-wide association analysis, we tested single-nucleotide
      polymorphisms for their association with resistance to antipsychotics defined
      according to American Psychiatric Association criteria. Two models were tested: a
      main model and an interaction model with the childhood trauma. RESULTS: Our
      analysis failed to demonstrate a significant relationship among 1,178,234 single
      nucleotide polymorphisms and treatment-resistance in both the main model and in
      the childhood trauma interaction model. CONCLUSION: Even though we could not find
      any significant association, treatment resistance has clinical relevance and it
      may be determined by the interaction between biological and non biological
      factors.

PMID- 28453391
TI  - Global Leadership Initiative on Malnutrition: Progress Report From ASPEN Clinical
      Nutrition Week 2017.

PMID- 28453390
TI  - The torments of the cohesin ring.
AB  - Cohesin is a ring-shaped protein complex which comprises the Smc1, Smc3 and Scc1
      subunits. It topologically embraces chromosomal DNA to connect sister chromatids
      and stabilize chromatin loops. It is required for proper chromosomal segregation,
      DNA repair and transcriptional regulation. We have recently reported that cohesin
      rings can adopt a "collapsed" rod-like conformation which is driven by the
      interaction between the Smc1 and Smc3 coiled coil arms and is regulated by post
      translational modifications. The "collapsed" conformation plays a role in cohesin
      ring assembly and its loading on the DNA. Here we speculate about the mechanism
      of cohesin's conformational transitions in relation to its loading on the DNA and
      draw parallels with other Smc-like complexes.

PMID- 28453392
TI  - Histamine as an Endothelium-Derived Relaxing Factor in Aged Mesenteric Lymphatic
      Vessels.
AB  - BACKGROUND: Knowledge of the mechanisms by which aging affects contracting
      lymphatic vessels remains incomplete; therefore, the functional role of histamine
      in the reaction of aged lymphatic vessels to increases in flow remains unknown.
      METHODS AND RESULTS: We measured and analyzed parameters of lymphatic
      contractility in isolated and pressurized rat mesenteric lymphatic vessels (MLVs)
      obtained from 9- and 24-month Fischer-344 rats under control conditions and after
      pharmacological blockade of nitric oxide (NO) by Nomega-Nitro-L-arginine methyl
      ester hydrochloride (L-NAME, 100 MUM) or/and blockade of histamine production by
      alpha-methyl-DL-histidine dihydrochloride (alpha-MHD, 10 MUM). We also
      quantitatively compared results of immunohistochemical labeling of the histamine
      producing enzyme, histidine decarboxylase (HDC) in adult and aged MLVs. Our data
      provide the first demonstration of an increased functional role of histamine as
      an endothelial-derived relaxing factor in aged MLVs, which appears in parallel
      with the abolished role of NO in the reactions of these lymph vessels to
      increases in flow. In addition, we found an increased expression of HDC in
      endothelium of aged MLVs. CONCLUSIONS: Our findings provide the basis for better
      understanding of the processes of aging in lymphatic vessels and for setting new
      important directions for investigations of the aging-associated disturbances in
      lymph flow and the immune response.

PMID- 28453394
TI  - Expression of miR-23a by apoptotic regulators in human cancer: A review.
AB  - MicroRNAs play fundamental roles in mammalian development, differentiation and
      cellular homeostasis by regulating essential processes such as proliferation,
      migration, metabolism, migration and cell death. These small non-coding RNAs are
      also responsible in RNA silencing, and in many developmental and pathological
      processes. Not surprisingly, miR-23a misexpression contributes to numerous
      diseases including cancer where certain miRNA genes have been classified as
      either oncogenes or tumor suppressor genes. Since a single microRNA is capable of
      targeting a large number of mRNA sequences, de-regulated miRNA expression has the
      ability to alter various transcripts and activate a wide range of cancer-related
      pathways. This review article documents reduced levels of mature miR-23a in
      various tumors, primarily due to epigenetic silencing or alterations in
      biogenesis pathways. Moreover, inhibition of miR-23a in stressed cells represent
      a general mechanism for inducing apoptosis and these microRNAs are showed to be
      regulated by molecular chaperon HSP70. Microarray expression analysis of miRNA
      overexpression or depletion is now used in the characterization of cancer
      development pathways and as a biomarker for early cancer detection.

PMID- 28453395
TI  - Association of vitamin D pathway SNPs and clinical response to interferon in a
      cohort of HBeAg-negative patients.
AB  - AIM: Vitamin D modulates biological processes; an influence of vitamin D levels
      and genetic variants was identified concerning hepatitis B virus infection. We
      evaluated the role of some SNPs of vitamin D pathway genes in some clinical
      features of hepatitis B affected patients treated with pegylated interferon.
      METHODS: We investigated SNPs in IL-28B, CYP27B1, CYP27A1, CYP24A1, VDBP and VDR
      genes, through real-time PCR. RESULTS:  VDRApaI SNP was associated to viral load
      and HBsAg presence at different timings. In logistic regression analyses, VDRApaI
      AA genotype predicted baseline viral load >6 Log IU/ml (marker of nonresponse),
      and both virological and biochemical responses. CONCLUSION: Pharmacogenetic data
      could help physicians in the prediction of patients with higher probability to
      achieve a good response.

PMID- 28453396
TI  - Pharmacogenetic analysis of hepatitis C virus related mixed cryoglobulinemia.
AB  - AIM: Mixed cryoglobulinemia (MC) is an extra hepatic hepatitis C virus related
      problem and different studies suggested genetics' role in predicting this
      complication. We evaluated the influence of SNPs in IL-28B, SLC29A1, SLC28A2,
      NT5C2, HNF4 and ABCB1 genes in MC prediction. PATIENTS & METHODS: SNPs were
      evaluated through real-time PCR. RESULTS:  ABCB1 (gene encoding P-glycoprotein)
      3435C>T SNP was associated with MC presence (p = 0.034): related to T allele
      carriers (CC vs CT/TT), we reached a p-value of 0.013. In the logistic regression
      analysis baseline viral load >600.000 IU/ml (p < 001), IL28B rs8099917/rs12979860
      TT/CC (p < 0.001), NT5 (gene encoding for 5' nucleotidase) 153 TC (p = 0.012) and
      ABCB1 3435 CT/TT (p = 0.034) genotypes predicted MC presence. CONCLUSION: These
      data could help clinicians to identify patients with higher probability to show
      MC extra hepatic complication.

PMID- 28453397
TI  - The three-person honeymoon in the letters of Katherine Philips and Sarah Scott.
AB  - This article explores two instances of the three-person honeymoon as a popular
      custom among the pre-nineteenth-century English gentry and aristocracy. It argues
      that the presence of the bride's sister or closest companion on the holiday
      allowed female friendships to survive the marriage of one or both parties, albeit
      in a drastically changed form. The comparison of a successful and a failed
      marriage demonstrates that the third wheel could intervene on the bride's behalf
      in cases of marital incompatibility or abuse.

PMID- 28453398
TI  - Assessment of passive drag in swimming by numerical simulation and analytical
      procedure.
AB  - The aim was to compare the passive drag-gliding underwater by a numerical
      simulation and an analytical procedure. An Olympic swimmer was scanned by
      computer tomography and modelled gliding at a 0.75-m depth in the streamlined
      position. Steady-state computer fluid dynamics (CFD) analyses were performed on
      Fluent. A set of analytical procedures was selected concurrently. Friction drag
      (Df), pressure drag (Dpr), total passive drag force (Df+pr) and drag coefficient
      (CD) were computed between 1.3 and 2.5 m . s-1 by both techniques. Df+pr ranged
      from 45.44 to 144.06 N with CFD, from 46.03 to 167.06 N with the analytical
      procedure (differences: from 1.28% to 13.77%). CD ranged between 0.698 and 0.622
      by CFD, 0.657 and 0.644 by analytical procedures (differences: 0.40-6.30%).
      Linear regression models showed a very high association for Df+pr plotted in
      absolute values (R2 = 0.98) and after log-log transformation (R2 = 0.99). The CD
      also obtained a very high adjustment for both absolute (R2 = 0.97) and log-log
      plots (R2 = 0.97). The bias for the Df+pr was 8.37 N and 0.076 N after
      logarithmic transformation. Df represented between 15.97% and 18.82% of the Df+pr
      by the CFD, 14.66% and 16.21% by the analytical procedures. Therefore, despite
      the bias, analytical procedures offer a feasible way of gathering insight on
      one's hydrodynamics characteristics.

PMID- 28453393
TI  - Cleavage and polyadenylation: Ending the message expands gene regulation.
AB  - Cleavage and polyadenylation (pA) is a fundamental step that is required for the
      maturation of primary protein encoding transcripts into functional mRNAs that can
      be exported from the nucleus and translated in the cytoplasm. 3'end processing is
      dependent on the assembly of a multiprotein processing complex on the pA signals
      that reside in the pre-mRNAs. Most eukaryotic genes have multiple pA signals,
      resulting in alternative cleavage and polyadenylation (APA), a widespread
      phenomenon that is important to establish cell state and cell type specific
      transcriptomes. Here, we review how pA sites are recognized and comprehensively
      summarize how APA is regulated and creates mRNA isoform profiles that are
      characteristic for cell types, tissues, cellular states and disease.

PMID- 28453399
TI  - Monitoring of carbon monoxide in residences with bulk wood pellet storage in the
      Northeast United States.
AB  - : The interest in biomass fuel is continuing to expand globally and in the
      northeastern United States as wood pellets are becoming a primary source of fuel
      for residential and small commercial systems. Wood pellets for boilers are often
      stored in basement storage rooms or large bag-type containers. Due to the
      enclosed nature of these storage areas, the atmosphere may exhibit increased
      levels of carbon monoxide. Serious accidents in Europe have been reported over
      the last decade in which high concentrations of carbon monoxide (CO) have been
      found in or near bulk pellet storage containers. The aim of this study was to
      characterize the CO concentrations in areas with indoor storage of bulk wood
      pellets. Data was obtained over approximately 7 months (December 2013 to June
      2014) at 25 sites in New Hampshire and Massachusetts: 16 homes using wood pellet
      boilers with indoor pellet storage containers greater than or equal to 3 ton
      capacity; 4 homes with wood pellet heating systems with outdoor pellet storage; 4
      homes using other heating fuels; and a university laboratory site. CO monitors
      were set up in homes to collect concentrations of CO in the immediate vicinity of
      wood pellet storage containers, and data were then compared to those of homes
      using fossil fuel systems. The homes monitored in this study provided a diverse
      set of housing stock spanning two and a half centuries of construction, with
      homes built from 1774 to 2013, representing a range of air exchange rates. The CO
      concentration data from each home was averaged hourly and then compared to a
      threshold of 9 ppm. While concentrations of CO were generally low for the homes
      studied, the need to properly design storage locations for pellets is and will
      remain a necessary component of wood pellet heating systems to minimize the risk
      of CO exposure. IMPLICATIONS: This paper is an assessment of carbon monoxide (CO)
      exposure from bulk wood pellet storage in homes in New Hampshire and
      Massachusetts. Understanding the CO concentrations in homes allows for better
      designs for storage bins and ventilation for storage areas. Hence, uniform
      policies for stored wood pellets in homes, schools, and businesses can be framed
      to ensure occupant safety. Currently in New York State rebates for the
      installation of wood pellet boilers are only provided if the bulk pellet storage
      is outside of the home, yet states such as New Hampshire, Vermont, and Maine
      currently do not have these restrictions.

PMID- 28453400
TI  - What's love got to do with it? Investigating consumer commitment in health care.
AB  - Building relationships with patients to create patient-centered care is critical
      to the success of health care organizations. A core element in relationships is
      commitment. Commitment may be based on affect and emotions, perceived costs, and
      even obligation. This research proposes that three types of commitment-affective,
      continuance, and normative commitment-differentially impact consumer purchase
      loyalty, attitudinal loyalty, and advocacy for a health care provider. To examine
      the impact of commitment type on consumer relationships, exploratory data were
      garnered and surveys were administered. Findings are discussed and implications
      for health care marketing managers in developing successful relationships with
      consumers are delineated.

PMID- 28453401
TI  - The effects of ego-resilience, social support, and depression on suicidal
      ideation among the elderly in South Korea.
AB  - South Korea's elderly suicide rate is not merely the highest among the member
      nations of the Organization for Economic Cooperation and Development, it is the
      highest in the world. This study analyzed the effect of ego-resilience and social
      support on depression and suicidal ideation of the elderly, providing baseline
      data to aid in the development of preventive programs on elder suicide. We found
      that ego-resilience is a strong inhibitor of suicidal ideation. Direct and
      indirect effects of social support on suicidal ideation were especially helpful
      for elders with mild depression.

PMID- 28453402
TI  - Evaluation of carbon emission reductions promoted by private driving restrictions
      based on automatic fare collection data in Beijing, China.
AB  - : Public transportation automatic fare collection (AFC) systems are able to
      continuously record large amounts of passenger travel information, providing
      massive, low-cost data for research on regulations pertaining to public
      transport. These data can be used not only to analyze characteristics of
      passengers' trips but also to evaluate transport policies that promote a travel
      mode shift and emission reduction. In this study, models combining card, survey,
      and geographic information systems (GIS) data are established with a research
      focus on the private driving restriction policies being implemented in an ever
      increasing number of cities. The study aims to evaluate the impact of these
      policies on the travel mode shift, as well as relevant carbon emission
      reductions. The private driving restriction policy implemented in Beijing is
      taken as an example. The impact of the restriction policy on the travel mode
      shift from cars to subways is analyzed through a model based on metro AFC data.
      The routing paths of these passengers are also analyzed based on the GIS method
      and on survey data, while associated carbon emission reductions are estimated.
      The analysis method used in this study can provide reference for the application
      of big data in evaluating transport policies. IMPLICATIONS: Motor vehicles have
      become the most prevalent source of emissions and subsequently air pollution
      within Chinese cities. The evaluation of the effects of driving restriction
      policies on the travel mode shift and vehicle emissions will be useful for other
      cities in the future. Transport big data, playing an important support role in
      estimating the travel mode shift and emission reduction considered, can help
      related departments to estimate the effects of traffic jam alleviation and
      environment improvement before the implementation of these restriction policies
      and provide a reference for relevant decisions.

PMID- 28453403
TI  - High Rate of Hepatitis B Virus Surface Antigenemia Among People Living with
      HIV/AIDS in Kakuri, Kaduna State, North West Nigeria.
AB  - Globally, increased incidence of liver disease caused by hepatitis B virus (HBV)
      is responsible for high morbidity and mortality among human immunodeficiency
      virus (HIV)-infected individuals. This is because both viruses share common
      routes of transmission. We determined prevalence of HBV-HIV coinfection and the
      influence of some risk factors on concomitant infection among people living with
      HIV in a treatment center in Kakuri, Kaduna State. Two hundred consenting
      individuals with HIV infection participated in the study. Fifty-seven males and
      143 females were screened using commercial hepatitis B virus surface antigen
      (HBsAg) rapid membrane-based immunoassay kit (FastepTM HBV). Seventeen patients
      tested positive to HBsAg (8.5%). There were more males (14.0%) than females
      (6.3%). Patients within 40-49 years of age had more coinfection (20.6%) compared
      to those older than 50 years who had the least prevalence (2.7%). Age of HBV/HIV
      coinfection was statistically significant (p = 0.02). Risk factors include no
      knowledge of HBV infection, sharing sharp objects, history of sexually
      transmitted diseases, history of surgeries, and no HBV immunization. High
      infection rate observed in this study underscores the need for public awareness,
      to educate people on modes of transmission. Routine screening is advocated for
      early HBV identification, as this will facilitate reduction of comorbidity and
      mortality resulting from opportunistic infection. Findings from this study
      support introduction of HBV vaccination as part of the Expanded Programme on
      Immunization in Nigeria.

PMID- 28453404
TI  - Effects of biofilter media depth and moisture content on removal of gases from a
      swine barn.
AB  - : Media depth (MD) and moisture content (MC) are two important factors that
      greatly influence biofilter performance. The purpose of this study was to
      investigate the combined effect of MC and MD on removing ammonia (NH3), hydrogen
      sulfide (H2S), and nitrous oxide (N2O) from swine barns. Biofiltration
      performance of different MDs and MCs in combination based on a mixed medium of
      wood chips and compost was monitored. A 3 * 3 factorial design was adopted, which
      included three levels of the two factors (MC: 45%, 55%, and 67% [wet basis]; MD:
      0.17, 0.33, and 0.50 m). Results indicated that high MC and MD could improve NH3
      removal efficiency, but increase outlet N2O concentration. When MC was 67%, the
      average NH3 removal efficiency of three MDs (0.17, 0.33, and, 0.50 m) ranged from
      77.4% to 78.7%; the range of average H2S removal efficiency dropped from 68.1
      90.0% (1-34 days of the test period) to 36.8-63.7% (35-58 days of the test
      period); and the average outlet N2O concentration increased by 25.5-60.1%. When
      MC was 55%, the average removal efficiency of NH3, H2S, and N2O for treatment
      with 0.33 m MD was 72.8 +/- 5.9%, 70.9 +/- 13.3%, and -18.9 +/- 8.1%,
      respectively; and the average removal efficiency of NH3, H2S, and N2O for
      treatment with 0.50 m MD was 77.7 +/- 4.2%, 65.8 +/- 13.7%, and -24.5 +/-12.1%,
      respectively. When MC was 45%, the highest average NH3 reduction efficiency among
      three MDs was 60.7% for 0.5 m MD, and the average N2O removal efficiency for
      three MDs ranged from -18.8% to -12.7%. In addition, the pressure drop of 0.33 m
      MD was significantly lower than that of 0.50 m MD (p < 0.05). To obtain high
      mitigation of NH3 and H2S and avoid elevated emission of N2O and large pressure
      drop, 0.33 m MD at 55% MC is recommended. IMPLICATIONS: The performances of
      biofilters with three different media depths (0.17, 0.33, and 0.50 m) and three
      different media moisture contents (45%, 55%, and 67% [wet basis]) were compared
      to remove gases from a swine barn. Using wood chips and compost mixture as the
      biofilters media, the combination of 0.33 m media depth and 55% media moisture
      content is recommended to obtain good reduction of NH3 and H2S, and to
      simultaneously prevent elevated emission of N2O and large pressure drop across
      the media.

PMID- 28453405
TI  - A meta-analysis of antimicrobial susceptibility profiles for pneumococcal
      pneumonia in sub-Saharan Africa.
AB  - BACKGROUND: Pneumonia causes an enormous burden of childhood disease globally,
      particularly in low- and middle-income countries. Pneumococcus is the most common
      bacterial aetiology of pneumonia; however, antimicrobials are limited and may not
      adequately address the local epidemiology of the region. AIM: To undertake a
      review and meta-analysis of pneumonia studies in sub-Saharan Africa to evaluate
      antimicrobial susceptibility patterns in childhood pneumonia. METHODS: Articles
      published in PubMed and Google between 2006 and 2016 which evaluated
      antimicrobial susceptibility profiles of pneumococcal pneumonia in children in
      sub-Saharan Africa were identified. The source of specimens, pathogens and
      antimicrobial susceptibility data were extracted. Pooled analysis of susceptible
      isolates was conducted using random effects models. RESULTS: Children from 15
      studies and 1634 isolates were included in the meta-analysis. In cases of
      childhood pneumonia, the mean overall proportion of penicillin susceptibility
      from invasive specimens of Streptococcus pneumoniae was 85.7% (95% CI 80.1-91.3),
      and of trimethoprim-sulfamethoxazole was 21.0% (95% CI 5.1-36.9). Compared with
      all S. pneumoniae specimens, penicillin susceptibility was 68.6% (95% CI 59.6
      77.5) and that of trimethoprim-sulfamethoxazole was 26.3% (95% CI 14.1-38.6).
      CONCLUSIONS: A high level of heterogeneity was detected, reflecting the paucity
      of data available. The establishment of national and regional diagnostic
      platforms to monitor antimicrobial susceptibility profiles for pneumonia as well
      as other invasive diseases will provide data with which to assess the relevance
      and adaptation of antimicrobial prescribing recommendations.

PMID- 28453407
TI  - Body esteem and self-esteem in middle-aged women.
AB  - The aims of the study were (a) to identify predictors of body esteem and (b) to
      expand on previous research by examining the link between global self-esteem and
      body esteem in a community-based sample of women in midlife. We found that body
      esteem in midlife women was predicted by body mass index (BMI), optimism, self
      esteem, and menopausal symptoms. Although BMI was the main predictor of body
      esteem in middle-aged women, global self-esteem was more strongly related to
      feelings about appearance and physical condition than feelings about body size.

PMID- 28453406
TI  - Crop Fertilization Impacts Epidemics and Optimal Latent Period of Biotrophic
      Fungal Pathogens.
AB  - Crop pathogens are known to rapidly adapt to agricultural practices. Although
      cultivar resistance breakdown and resistance to pesticides have been broadly
      studied, little is known about the adaptation of crop pathogens to fertilization
      regimes and no epidemiological model has addressed that question. However, this
      is a critical issue for developing sustainable low-input agriculture. In this
      article, we use a model of life history evolution of biotrophic wheat fungal
      pathogens in order to understand how they could adapt to changes in fertilization
      practices. We focus on a single pathogen life history trait, the latent period,
      which directly determines the amount of resources allocated to growth and
      reproduction along with the speed of canopy colonization. We implemented three
      fertilization scenarios, corresponding to major effects of increased nitrogen
      fertilization on crops: (i) increase in nutrient concentration in leaves, (ii)
      increase of leaf lifespan, and (iii) increase of leaf number (tillering) and size
      that leads to a bigger canopy size. For every scenario, we used two different
      fitness measures to identify putative evolutionary responses of latent period to
      changes in fertilization level. We observed that annual spore production
      increases with fertilization, because it results in more resources available to
      the pathogens. Thus, diminishing the use of fertilizers could reduce biotrophic
      fungal epidemics. We found a positive relationship between the optimal latent
      period and fertilization when maximizing total spore production over an entire
      season. In contrast, we found a negative relationship between the optimal latent
      period and fertilization when maximizing the within-season exponential growth
      rate of the pathogen. These contrasting results were consistent over the three
      tested fertilization scenarios. They suggest that between-strain diversity in the
      latent period, as has been observed in the field, may be due to diversifying
      selection in different cultural environments.

PMID- 28453408
TI  - Salmonella Typhi Associated Endogenous Endophthalmitis: A Case Report and a
      Review of Literature.
AB  - AIM: To report a rare case of Salmonella typhi associated endogenous
      endophthalmitis in an immunocompetent male and to review the available
      literature. METHODS: Retrospective chart review. RESULTS: A 28-year-old
      immunocompetent male presented with a 3-day-old history of pain, redness and
      diminished vision in his left eye. Conjunctival chemosis, corneal haze, and
      hypopyon were noted and yellowish exudates filled the vitreous cavity. A detailed
      elicitation of history revealed that patient had been treated for enteric fever
      that presented with diarrhea and fever, two weeks prior to current presentation.
      Blood and vitreous cultures grew Gram negative bacilli, identified as S. typhi.
      Despite intensive intravitreal and systemic antibiotic therapy, an evisceration
      had to be performed. CONCLUSIONS: Endogenous endophthalmitis can be one of the
      rare sequelae of enteric fever and may present in the acute and relapsing phases
      and often times have a rapidly fulminant course with poor visual outcomes.

PMID- 28453409
TI  - It's Time for EMS to Administer Ketamine Analgesia.

PMID- 28453410
TI  - Does Lymphedema Severity Affect Quality of Life? Simple Question. Challenging
      Answers.
AB  - PURPOSE: Lymphedema can have a negative impact on the function and quality of
      life (QOL) of patients, but most studies have examined lymphedema as a binary
      variable, rather than a multidimensional disease that ranges in severity. This
      study explored the potential impact of lymphedema severity on function and
      overall QOL. METHODS AND RESULTS: Of the 54 lymphedema patients recruited, 40
      reported their most severe swelling to be in a limb. These participants underwent
      bioimpedance measurement (L-Dex(r)) and completed either the disabilities of the
      arm, shoulder, and hand (DASH) questionnaire or the lower extremity functional
      scale (LEFS). All participants completed the lymphedema quality of life
      questionnaire (LYMQOL) and were categorized for severity using International
      Society of Lymphology (ISL) stage. Mild (Stage 0-I), moderate (Stage IIa), and
      severe (Stage IIb-III) lymphedema accounted for 22%, 50%, and 28% of the
      participants, respectively. The median [inter-quartile range (IQR)] L-Dex score
      was 17.8 (6.6-52.7) for arm participants and 36.4 (15.9-93.5) for leg
      participants. Apart from a mild difference in LYMQOL ARM Appearance domain (p =
      0.046), ISL staging did not have any relationship with DASH, LEFS, and LYMQOL
      domains, or overall QOL. Higher L-Dex was related to poorer function (DASH p =
      0.015; LEFS p = 0.019), but was not related to overall QOL of limb lymphedema
      participants (p > 0.05). CONCLUSIONS: Lymphedema severity did not appear to
      impact QOL. ISL staging may not be used alone to describe lymphedema severity.
      Other methods such as bioimpedance, imaging, and self-report of symptoms are
      required to fully evaluate the impact of lymphedema severity on function and QOL.

PMID- 28453412
TI  - Identification and Characterization of Citrus tristeza virus Isolates Breaking
      Resistance in Trifoliate Orange in California.
AB  - Most Citrus tristeza virus (CTV) isolates in California are biologically mild and
      symptomless in commercial cultivars on CTV tolerant rootstocks. However, to
      better define California CTV isolates showing divergent serological and genetic
      profiles, selected isolates were subjected to deep sequencing of small RNAs. Full
      length sequences were assembled, annotated and trifoliate orange resistance
      breaking (RB) isolates of CTV were identified. Phylogenetic relationships based
      on their full genomes placed three isolates in the RB clade: CA-RB-115, CA-RB
      AT25, and CA-RB-AT35. The latter two isolates were obtained by aphid transmission
      from Murcott and Dekopon trees, respectively, containing CTV mixtures. The
      California RB isolates were further distinguished into two subclades. Group I
      included CA-RB-115 and CA-RB-AT25 with 99% nucleotide sequence identity with RB
      type strain NZRB-G90; and group II included CA-RB-AT35 with 99 and 96% sequence
      identity with Taiwan Pumelo/SP/T1 and HA18-9, respectively. The RB phenotype was
      confirmed by detecting CTV replication in graft-inoculated Poncirus trifoliata
      and transmission from P. trifoliata to sweet orange. The California RB isolates
      induced mild symptoms compared with severe isolates in greenhouse indexing tests.
      Further examination of 570 CTV accessions, acquired from approximately 1960 and
      maintained in planta at the Central California Tristeza Eradication Agency,
      revealed 16 RB positive isolates based on partial p65 sequences. Six isolates
      collected from 1992 to 2011 from Tulare and Kern counties were CA-RB-115-like;
      and 10 isolates collected from 1968 to 2010 from Riverside, Fresno, and Kern
      counties were CA-RB-AT35-like. The presence of the RB genotype is relevant
      because P. trifoliata and its hybrids are the most popular rootstocks in
      California.

PMID- 28453411
TI  - Pooled Analysis of the Prognostic and Predictive Effects of TP53 Comutation
      Status Combined With KRAS or EGFR Mutation in Early-Stage Resected Non-Small-Cell
      Lung Cancer in Four Trials of Adjuvant Chemotherapy.
AB  - Purpose Our previous work evaluated individual prognostic and predictive roles of
      TP53, KRAS, and EGFR in non-small-cell lung cancer (NSCLC). In this analysis, we
      explore the prognostic and predictive roles of TP53/KRAS and TP53/EGFR
      comutations in randomized trials of adjuvant chemotherapy versus observation.
      Patients and Methods Mutation analyses (wild-type [WT] and mutant) for TP53,
      KRAS, and EGFR were determined in blinded fashion in multiple laboratories.
      Primary and secondary end points of pooled analysis were overall survival and
      disease-free survival. We evaluated the role of TP53/KRAS comutation in all
      patients and in the adenocarcinoma subgroup as well as the TP53/EGFR comutation
      in adenocarcinoma only through a multivariable Cox proportional hazards model
      stratified by trial. Results Of 3,533 patients with NSCLC, 1,181 (557 deaths) and
      404 (170 deaths) were used for TP53/KRAS and TP53/EGFR analyses. For TP53/KRAS
      mutation status, no prognostic effect was observed ( P = .61), whereas a
      borderline predictive effect ( P = .04) was observed with a deleterious effect of
      chemotherapy with TP53/KRAS comutations versus WT/WT (hazard ratio, 2.49 [95% CI,
      1.10 to 5.64]; P = .03). TP53/EGFR comutation in adenocarcinoma was neither
      prognostic ( P = .83), nor significantly predictive ( P = .86). Similar results
      were observed for both groups for disease-free survival. Conclusion We could
      identify no prognostic effect of the KRAS or EGFR driver and TP53 tumor
      suppressor comutation. Our observation of a potential negative predictive effect
      of TP53/KRAS comutation requires validation.

PMID- 28453413
TI  - Assessing the Adequacy of Absorbable Braided Suture for Laparoscopic High
      Ligation in Rabbits.
AB  - PURPOSE: Our previous work demonstrated that intentional peritoneal injury
      reduces the incidence of recurrence of a patent processus vaginalis even after
      removal of the suture. Therefore, the necessity of permanent suture has been
      brought into question because of the risk of suture granuloma formation. The
      purpose of this study was to evaluate the efficacy of absorbable, braided versus
      permanent, braided suture in a rabbit survival model of laparoscopic percutaneous
      ligation of the processus vaginalis with intentional peritoneal injury. MATERIALS
      AND METHODS: Eighteen New Zealand White rabbits underwent bilateral subcutaneous
      endoscopically assisted ligation (SEAL) of the internal ring. Before SEAL,
      peritoneal injury was caused with endoscopic shears. Each animal was randomized
      to receive absorbable braided suture on one side and permanent braided suture on
      the contralateral side. The rabbits were survived for 8 weeks to allow for
      complete hydrolysis of the absorbable suture. Necropsy was performed during which
      the integrity of the repair was assessed with insufflation of carbon dioxide up
      to 30 mm Hg. McNemar's test for paired data was performed for statistical
      analysis. RESULTS: Seventeen rabbits survived 8 weeks. One rabbit died in the
      early postoperative period because of urinary tract obstruction. After
      insufflation, four (24%) recurrences were present in the absorbable group and two
      (12%) recurrences were present in the permanent group. This difference was not
      statistically significant (P = .50). Both rabbits with a recurrence on the side
      with permanent suture also had a recurrence with absorbable suture on the
      contralateral side. In all rabbits, the permanent suture was identified, whereas
      there was no visual evidence of absorbable suture. CONCLUSIONS: A trend toward a
      higher recurrence rate with the use of absorbable braided suture was present,
      although, in this study, the finding was not statistically significant. Caution
      should be used when considering implementation of absorbable suture for
      laparoscopic inguinal hernia repair.

PMID- 28453414
TI  - Innate Immune Gene Transcript Level Associated with the Infection of Macrophages
      with Ectromelia Virus in Two Different Mouse Strains.
AB  - Poxviruses have evolved numerous mechanisms to avoid the immune response of the
      infected host, and many of these mechanisms have not been fully described. Here,
      we studied the transcriptional response of innate immune genes in BALB/c and
      C57BL/6 peritoneal macrophages following infection with the Moscow strain of
      ectromelia virus (ECTV-Mos) with the aim of delineating innate immune genes that
      contribute to the difference between susceptibility and resistance to lethal
      infection. We show a generalized downregulation of many genes in four categories
      (toll-like receptor signaling, NOD-like receptor signaling, RIG-I-like receptor
      signaling, and type I interferon signaling) of antiviral innate immune receptors,
      downstream signaling pathways, and responsive components. Two important
      observations were made. First, 14 innate antiviral genes were differentially
      expressed with fold change upregulation of two and above occurring in C57BL/6
      mice, known to be resistant to ECTV-Mos infection, whereas the same genes were
      downregulated in BALB/c mice with fold change of two and below. Second, the
      cathepsin group of genes was downregulated in both strains of mice but with
      profound fold changes of 17, 38, and 62 downregulation for CtsL, CtsB, and CtsS,
      respectively, in C57BL/6 mice. We show that a poxvirus profoundly downregulates
      both the mRNA and protein expression of these three cathepsins and this change
      appears to support virus replication. Based on these data we propose that the
      variations in gene expression observed may contribute to the difference in
      resistance/susceptibility between BALB/c and C57BL/6 mice to lethal infection by
      ECTV-Mos.

PMID- 28453416
TI  - Nurse Research Rounds: In the Spirit of Inquiry.
AB  - Nurses deliver a point-of-care service to patients. The nursing staff work
      extensive schedules and do not have time to research a clinical question to help
      support patient care. This article describes the implementation of the first
      research service that supports evidence-based practice at Georgia's second
      largest hospital. Inspired by a similar service at a children's hospital in 2014,
      the first year of nurse research rounds provides clinicians a new research
      service in their clinical setting.

PMID- 28453415
TI  - Connecting the Libraries and Athletics through Instruction and Outreach.
AB  - This column describes the approaches taken by librarians and staff at James
      Madison University (JMU) Libraries & Educational Technologies (LET) to extend
      library support to university athletics. The model resembles that used for
      outreach to academic programs and was first adapted to the semi-clinical,
      nonacademic Strength & Conditioning Department, then to JMU Athletics as a whole.
      Librarians offered targeted instructional sessions, orientations, and
      asynchronous learning modules embedded in the learning management system. This
      new relationship has provided an opportunity for broader collaboration,
      increasing LET's presence across campus.

PMID- 28453417
TI  - Experience, Challenges, and Opportunities of Being Fully Embedded in a User
      Group.
AB  - Embedded librarian models can assume different forms and levels, depending on
      patron needs and a library's choice of delivery services. An academic health
      sciences library decided to enhance its service delivery model by integrating a
      librarian into the College of Pharmacy, approximately 250 miles away from the
      main library. This article describes the embedded librarian's first-year
      experience, challenges, and opportunities working as a library faculty in the
      college. The comparison of one-year recorded statistics on preembedded and
      postembedded activities demonstrated the effectiveness and impact of such an
      embedded librarian model.

PMID- 28453418
TI  - Creative Curriculum: The Experience of Writing and Teaching Formative Objective
      Structured Clinical Examinations (FOSCEs).
AB  - The launch of the revised medical school curriculum in fall 2014 provided new
      opportunities for librarians to collaborate with clinical faculty. As a result of
      past informatics instruction embedded in the first-year curriculum, librarians
      were invited to expand this content as part of a new Formative Objective
      Structured Clinical Examination (FOSCE) initiative. This article describes the
      stages of this project from writing and teaching the FOSCE informatics cases to
      improvements which were made after the first year. A description of the overall
      curriculum and information about lessons learned in each of these stages is
      included.

PMID- 28453419
TI  - Metaliteracy in Practice, edited by Trudi E. Jacobson and Thomas P. Mackey.

PMID- 28453421
TI  - Being Evidence Based in Library and Information Practice, edited by Denise
      Koufogiannakis and Alison Brettle.

PMID- 28453422
TI  - Health Sciences Library Support of a University Common Reading Program: A Case
      Study.
AB  - Common reading programs have become increasingly popular on college and
      university campuses as a means for increasing student engagement, retention, and
      success. This article describes the characteristics, goals, and benefits of
      common reading programs and provides examples from the literature of academic
      library involvement in them. Finally, an example is provided of how one academic
      health sciences library participated in its institution's First-Year Summer
      Reading program.

PMID- 28453423
TI  - Library Security: Better Communication, Safer Facilities, edited by Steve
      Albrecht.

PMID- 28453424
TI  - A Multicomponent Library Resource Model to Enhance Academic Global Health
      Education Among Residency Programs.
AB  - Global health is becoming an increasingly important component of medical
      education. Medical libraries have an opportunity to assist global health
      residents with their information needs, but first it is important to identify
      what those needs are and how best they can be addressed. This article reports a
      collaboration between global health faculty and an academic medical librarian to
      assess the information needs of global health pathway residents and how
      assessment data are used to create a multicomponent program designed to enhance
      global health education.

PMID- 28453425
TI  - Library Linked Data: Early Activity & Development, edited by Erik T. Mitchell.

PMID- 28453426
TI  - Taking Chances: A New Librarian and Curriculum Redesign.
AB  - As technology becomes ubiquitous in designing and delivering medical school
      curricula, health sciences librarians can embrace emerging opportunities for
      participation in curriculum design. A new medical librarian at Michigan State
      University Libraries engaged her user base outside of established duties, learned
      new skills, and challenged preconceived notions about librarians' roles. In the
      process, she became a partner in copyright education, amended license agreements
      for enhanced curricular multimedia use, and facilitated curriculum mapping
      through taxonomy building. These projects helped create the informational
      foundation for a novel hybrid medical education curriculum and introduced new
      curricular roles for the librarian.

PMID- 28453427
TI  - VisionCite: A Vision Science-Related Database.
AB  - VisionCite is a database dedicated to the visual sciences. This paid subscription
      database provides bibliographic information for optometry and ophthalmology
      related resources and is maintained by the Illinois College of Optometry (ICO)
      Library. A sample search is provided, highlighting different features of the
      newly redesigned database.

PMID- 28453428
TI  - Reality Check: Basics of Augmented, Virtual, and Mixed Reality.
AB  - Augmented, virtual, and mixed reality applications all aim to enhance a user's
      current experience or reality. While variations of this technology are not new,
      within the last few years there has been a significant increase in the number of
      artificial reality devices or applications available to the general public. This
      column will explain the difference between augmented, virtual, and mixed reality
      and how each application might be useful in libraries. It will also provide an
      overview of the concerns surrounding these different reality applications and
      describe how and where they are currently being used.

PMID- 28453429
TI  - Anti-microbial coating innovations to prevent infectious diseases (AMiCI): Cost
      action ca15114.
AB  - Worldwide, millions of patients are affected annually by healthcare-associated
      infection (HCAI), impacting up to 80,000 patients in European Hospitals on any
      given day. This represents not only public health risk, but also an economic
      burden. Complementing routine hand hygiene practices, cleaning and disinfection,
      antimicrobial coatings hold promise based, in essence, on the application of
      materials and chemicals with persistent bactericidal or -static properties onto
      surfaces or in textiles used in healthcare environments. The focus of
      considerable commercial investment and academic research energies, such
      antimicrobial coating-based approaches are widely believed to have potential in
      reduction of microbial numbers on surfaces in clinical settings. This belief
      exists despite definitive evidence as to their efficacy and is based somewhat on
      positive studies involving, for example, copper, silver or gold ions, titanium or
      organosilane, albeit under laboratory conditions. The literature describes
      successful delay and/or prevention of recontamination following conventional
      cleaning and disinfection by problematic microbes such as methicillin-resistant
      Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE), among
      others. However, there is a scarcity of studies assessing antimicrobial surfaces
      other than copper in the clinical environment, and a complete lack of published
      data regarding the successful implementation of these materials on clinically
      significant outcomes (including HCAI). Through its Cooperation in Science and
      Technology program (COST), the European Commission has funded a 4-year initiative
      to establish a network of stakeholders involved in development, regulation and
      use of novel anti-microbial coatings for prevention of HCAI. The network (AMiCI)
      comprises participants of more than 60 universities, research institutes and
      companies across 29 European countries and, to-date, represents the most
      comprehensive consortium targeting use of these emergent technologies in
      healthcare settings. More specifically, the network will prioritise coordinated
      research on the effects (both positive and negative) of antimicrobial coatings in
      healthcare sectors; know-how regarding availability and mechanisms of action of
      (nano)-coatings; possible adverse effects of such materials (e.g., potential
      emergence of microbial resistance or emission of toxic agents into the
      environment); standardised performance assessments for antimicrobial coatings;
      identification and dissemination of best practices by hospitals, other clinical
      facilities, regulators and manufacturers.

PMID- 28453430
TI  - H2B monoubiquitination: t'ub or not t'ub for inducible enhancers.
AB  - Recently, we reported the unexpected finding that the monoubiquitination of
      histone H2B (H2Bub1) regulates inducible enhancers. Here, we propose a conceptual
      framework to reconcile the apparently discrepant roles of H2Bub1 in transcription
      initiation and elongation, and we discuss how H2Bub1 could regulate cellular
      processes linked to non-coding transcription.

PMID- 28453431
TI  - Safety and Efficacy of Irreversible Electroporation for the Treatment of
      Hepatocellular Carcinoma Not Amenable to Thermal Ablation Techniques: A
      Retrospective Single-Center Case Series.
AB  - Purpose To assess the safety and efficacy of irreversible electroporation (IRE)
      in the treatment of patients with inoperable hepatocellular carcinoma (HCC) who
      are ineligible for thermal ablative techniques. Materials and Methods This
      retrospective study was approved by an ethics review board, and the requirement
      to obtain informed written consent was waived. From March 2012 to June 2015, 58
      patients (median age, 65.4 years; range 41.6-90 years) with cirrhosis received
      IRE for the treatment of 75 HCC tumors. The median tumor diameter was 24 mm
      (range, 6-90 mm). IRE was selected because of tumor location (48 patients) or the
      patient's poor general condition (10 patients). Treatment response was assessed
      with magnetic resonance (MR) imaging 1 month after treatment and every 3 months
      thereafter. Overall local tumor progression-free survival (PFS) per nodule
      (including initial treatment failures) was assessed by using the Kaplan-Meier
      method. The marginal Cox proportional hazards model was used to assess the
      factors associated with overall local tumor PFS. Complications were recorded and
      graded according to the Clavien-Dindo classification. Results Of 75 tumors, 58
      (77.3%), 67 (89.3%), and 69 (92%) were completely ablated after one, two, and
      three IRE procedures, respectively. After a median follow-up of 9 months (range,
      3 days to 31 months), the 6- and 12-month overall local tumor PFS rates for the
      75 treated nodules were 87% (95% confidence interval [CI]: 77%, 93%) and 70% (95%
      CI: 56%, 81%), respectively. A preablative serum alpha-fetoprotein level higher
      than 200 ng/mL (hazard ratio: 9.94 [95% CI: 2.82, 35.06], P = .0004) was the only
      factor linked with overall local tumor PFS. Complications occurred in 11 of the
      58 patients (19%) and were classified as grade I in three patients, grade II in
      five patients, grade IV in two patients, and grade V in one patient. The three
      (5.2%) complications classified as grade III or higher were liver failures
      occurring in patients with Child-Pugh class B disease; one led to death.
      Conclusion IRE offers safe, complete ablation of HCC tumors in patients with
      contraindications to other commonly used ablative techniques. (c) RSNA, 2017
      Online supplemental material is available for this article.

PMID- 28453432
TI  - Multiregional Radiogenomic Assessment of Prostate Microenvironments with
      Multiparametric MR Imaging and DNA Whole-Exome Sequencing of Prostate Glands with
      Adenocarcinoma.
AB  - Purpose To assess the underlying genomic variation of prostate gland
      microenvironments of patients with prostate adenocarcinoma in the context of
      colocalized multiparametric magnetic resonance (MR) imaging and histopathologic
      assessment of normal and abnormal regions by using whole-exome sequencing.
      Materials and Methods Six patients with prostate adenocarcinoma who underwent
      robotic prostatectomy with whole-mount preservation of the prostate were
      identified, which enabled spatial mapping between preoperative multiparametric MR
      imaging and the gland. Four regions of interest were identified within each
      gland, including regions found to be normal and abnormal via histopathologic
      analysis. Whole-exome DNA sequencing (>50 times coverage) was performed on each
      of these spatially targeted regions. Radiogenomic analysis of imaging and
      mutation data were performed with hierarchical clustering, phylogenetic analysis,
      and principal component analysis. Results Radiogenomic multiparametric MR imaging
      and whole-exome spatial characterization in six patients with prostate
      adenocarcinoma (three patients, Gleason score of 3 + 4; and three patients,
      Gleason score of 4 + 5) was performed across 23 spatially distinct regions.
      Hierarchical clustering separated histopathologic analysis-proven high-grade
      lesions from the normal regions, and this reflected concordance between
      multiparametric MR imaging and resultant histopathologic analysis in all
      patients. Seventy-seven mutations involving 29 cancer-associated genes across the
      23 spatially distinct prostate samples were identified. There was no significant
      difference in mutation load in cancer-associated genes between regions that were
      proven to be normal via histopathologic analysis (34 mutations per sample +/-
      19), mildly suspicious via multiparametric MR imaging (37 mutations per sample +/
      21), intermediately suspicious via multiparametric MR imaging (31 mutations per
      sample +/- 15), and high-grade cancer (33 mutations per sample +/- 18) (P = .30).
      Principal component analysis resolved samples from different patients and further
      classified samples (regardless of histopathologic status) from prostate glands
      with Gleason score 3 + 4 versus 4 + 5 samples. Conclusion Multiregion spatial
      multiparametric MR imaging and whole-exome radiogenomic analysis of prostate
      glands with adenocarcinoma shows a continuum of mutations across regions that
      were found via histologic analysis to be high grade and normal. (c) RSNA, 2017
      Online supplemental material is available for this article.

PMID- 28453433
TI  - Diagnostic Accuracy of Selective 3-T MR Neurography-guided Retroperitoneal
      Genitofemoral Nerve Blocks for the Diagnosis of Genitofemoral Neuralgia.
AB  - Purpose To determine if 3-T magnetic resonance (MR) neurography-guided
      retroperitoneal genitofemoral nerve (GFN) blocks are safe and effective for the
      diagnosis of genitofemoral neuralgia. Materials and Methods Following
      institutional review board approval and informed consent, 26 subjects (16 men, 10
      women; mean age, 42 years [range, 24-78 years]; mean body mass index, 28 kg/m2
      [range, 20-35 kg/m2]) with intractable groin pain were included. By using a 3-T
      MR imaging system, intermediate-weighted turbo spin-echo pulse sequences, and MR
      conditional needles, diagnostic MR neurography-guided GFN blocks were performed
      in the retroperitoneum. Outcome variables included technical success, procedure
      time, complications, and rates of positive and negative GFN blocks in association
      with therapeutic outcomes. For the assessment of a learning curve, Mann-Whitney
      test was used. P values <= .05 were considered to indicate a statistically
      significant difference. Results In 26 subjects, 30 retroperitoneal GFN blocks
      were performed. Twelve (40%) were performed with an anterior needle path, 12
      (40%) with a lateral needle path, and six (20%) with a posterior needle path. GFN
      blocks were technically successful in 24 of 26 (92%) subjects, achieving
      appropriate scrotal anesthesia. No complications occurred. The time required for
      a GFN block was 40 minutes (range, 18-67 minutes). The rate of a successful GFN
      intervention after a positive GFN block was 88% (14 of 16). The rate of a
      successful intervention of an alternative target after a negative GFN block was
      71% (five of seven). Conclusion Selective retroperitoneally directed MR
      neurography-guided GFN blocks are safe and effective with high technical success
      and positive effect on surgical decision making in patients with presumed
      genitofemoral neuralgia. (c) RSNA, 2017 Online supplemental material is available
      for this article.

PMID- 28453436
TI  - The maths of memory.
AB  - Mathematical modeling reveals that long-term immunological memory is maintained
      in a manner that is even more dynamic than previously thought.

PMID- 28453437
TI  - Umbilical cord as human cell source for mitral valve tissue engineering - venous
      vs. arterial cells.
AB  - Around 2% of the population in developed nations are affected by mitral valve
      disease and available valvular replacements are not designed for the
      atrioventricular position. Recently our group developed the first tissue
      engineered heart valve (TEHV) specifically designed for the mitral position - the
      TexMi valve. The valve recapitulates the main components of the native valve,
      i.e. annulus, asymmetric leaflets and the crucial chordae tendineae. In the
      present study, we evaluated the human umbilical cord as a clinically applicable
      cell source for the TexMi valve. Valves produced with cells isolated from human
      umbilical cord veins (HUVs) and human umbilical cord arteries (HUAs) were
      conditioned for 21 days in custom-made bioreactors and evaluated in terms of
      extracellular matrix (ECM) composition and mechanical properties. In addition,
      static cell-laden fibrin discs were molded to investigate cell-mediated tissue
      contraction and differences in ECM production. HUA and HUV cells were able to
      deliver functional valves with a rich ECM composed mainly of collagen.
      Particularly noteworthy was the synthesis of elastin, which has been observed
      rarely in TEHV. The elastin synthesis was significantly higher in TexMi valves
      produced with HUV cells and therefore the HUV is considered to be the preferred
      cell source.

PMID- 28453434
TI  - Follicular morphological characteristics may be associated with invasion in
      follicular thyroid neoplasms with papillary-like nuclear features.
AB  - The newly proposed nomenclature and diagnostic criteria for encapsulated
      follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive
      follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could
      improve the consistency and accuracy of diagnosing this entity. Diagnosis of
      NIFTP requires evaluation of the complete tumor border or capsule. The presence
      of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear
      features has been recently discussed by many authors. In this study, we examined
      the predictive value and association of follicular morphological characteristics
      with the tumor invasion. In addition, we analyzed the association between tumor
      encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases
      of FVPTC were included in the study. The tumors were grouped based on the
      presence of tumor capsule and characteristics of tumor border, as 1) completely
      encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3)
      infiltrative tumors without a capsule. Clinicopathological features,
      histomorphological features [nuclear criteria, minor diagnostic features,
      follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular
      alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were
      significantly more frequently seen in encapsulated tumors with invasion (p =
      0.008). The nuclear features were not associated with the presence of
      encapsulation and characteristics of tumor border. BRAF mutation was more
      frequent in infiltrative tumors, while NRAS mutation was more frequent in
      encapsulated tumors, but the results were not statistically significant (p =
      0.917). In conclusion, FOPBC histomorphological feature may be associated with
      tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis
      may prevent inadequate treatment in these patients.

PMID- 28453438
TI  - Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic
      pain.

PMID- 28453439
TI  - Evaluation of serum cortisol biological variation in the evening withdrawal.

PMID- 28453440
TI  - Median Analysis of Repeated Measures Associated with Recurrent Events in Presence
      of Terminal Event.
AB  - Recurrent events are often encountered in medical follow up studies. In addition,
      such recurrences have other quantities associated with them that are of
      considerable interest, for instance medical costs of the repeated
      hospitalizations and tumor size in cancer recurrences. These processes can be
      viewed as point processes, i.e. processes with arbitrary positive jump at each
      recurrence. An analysis of the mean function for such point processes have been
      proposed in the literature. However, such point processes are often skewed,
      leading to median as a more appropriate measure than the mean. Furthermore, the
      analysis of recurrent event data is often complicated by the presence of death.
      We propose a semiparametric model for assessing the effect of covariates on the
      quantiles of the point processes. We investigate both the finite sample as well
      as the large sample properties of the proposed estimators. We conclude with a
      real data analysis of the medical cost associated with the treatment of ovarian
      cancer.

PMID- 28453441
TI  - Fetal cardiac time intervals in healthy pregnancies - an observational study by
      fetal ECG (Monica Healthcare System).
AB  - BACKGROUND: Fetal electrocardiogram (fECG) can detect QRS signals in fetuses from
      as early as 17 weeks' gestation; however, the technique is limited by the minute
      size of the fetal signal relative to noise ratio. The aim of this study was to
      evaluate precise fetal cardiac time intervals (fCTIs) with the help of a newly
      developed fetal ECG device (Monica Healthcare System). METHODS: In a prospective
      manner we included 15-18 healthy fetuses per gestational week from 32 weeks
      onwards. The small and wearable Monica AN24 monitoring system uses standard ECG
      electrodes placed on the maternal abdomen to monitor fECG, maternal ECG and
      uterine electromyogram (EMG). Fetal CTIs were estimated on 1000 averaged fetal
      heart beats. Detection was deemed successful if there was a global signal loss of
      less than 30% and an analysis loss of the Monica AN24 signal separation analysis
      of less than 50%. Fetal CTIs were determined visually by three independent
      measurements. RESULTS: A total of 149 fECGs were performed. After applying the
      requirements 117 fECGs remained for CTI analysis. While the onset and termination
      of P-wave and QRS-complex could be easily identified in most ECG patterns (97%
      for P-wave, PQ and PR interval and 100% for QRS-complex), the T-wave was
      detectable in only 41% of the datasets. The CTI results were comparable to other
      available methods such as fetal magnetocardiography (fMCG). CONCLUSIONS: Although
      limited and preclinical in its use, fECG (Monica Healthcare System) could be an
      additional useful tool to detect precise fCTIs from 32 weeks' gestational age
      onwards.

PMID- 28453442
TI  - 3,7-Isoquinoline quinones from the ascidian tunicate Ascidia virginea.
AB  - A new isoquinoline quinone system and its iodinated derivatives were isolated
      from the ascidian tunicate Ascidia virginea Muller 1776 (Phlebobranchia:
      Ascidiidae). Structures were elucidated by spectroscopic methods and
      derivatization reactions. Ascidine A (3,7-dihydro-1,8-dihydroxy-4-(4'
      hydroxyphenyl)isoquinoline-3,7-dione (1), ascidine B (3,7-dihydro-1,8-dihydroxy-4
      (4'-hydroxy-3'-iodophenyl)isoquinoline-3,7-dione (2), and ascidine C (3,7-dihydro
      1,8-dihydroxy-4-(4'-hydroxy-3',5'-diiodophenyl)isoquinoline-3,7-dione (3)
      represent a novel type of tyrosine-derived alkaloids.

PMID- 28453443
TI  - Plasmon field enhancement oscillations induced by strain-mediated coupling
      between a quantum dot and mechanical oscillator.
AB  - We utilize the surface plasmon field of a metal nanoparticle (MNP) to show strain
      mediated coupling in a quantum dot-mechanical resonator hybrid system including a
      quantum dot (QD) embedded within a conical nanowire (NW) and a MNP in the
      presence of an external field. Based on the numerical solutions of the master
      equation, we find that a slow oscillation, originating from the strain-mediated
      coupling between the QD and the NW, appears in the time evolution of the plasmon
      field enhancement. The results show that the period (about [Formula: see text])
      of the slow oscillation is equal to that of the mechanical resonator of NW, which
      suggests that the time-resolved measurement of the plasmon field enhancement can
      be easily achieved based on the current experimental conditions. Its amplitude
      increases with the increasing strain-mediated coupling strength, and under
      certain conditions there is a linear relationship between them. The slow
      oscillation of the plasmon field enhancement provides valuable tools for
      measurements of the mechanical frequency and the strain-mediated coupling
      strength.

PMID- 28453444
TI  - Electrode distance regulates the anodic growth of titanium dioxide (TiO2)
      nanotubes.
AB  - Electrochemical anodization of titanium has been used widely to produce self
      organized TiO2 nanotube arrays. Many experimental parameters, such as anodizing
      voltage and electrolyte composition, have been investigated extensively in the
      anodic growth of TiO2 nanotubes. The effect of electrode distance on the anodic
      growth of TiO2 nanotube arrays, however, remains elusive. This could be an
      important problem when in situ growth of TiO2 nanotubes is required in
      microdevices. Here, we show that decreasing the electrode distance at a constant
      anodizing voltage enhances the anodic growth of TiO2 nanotubes and the change of
      nanotube structures becomes more sensitive to the electrode distance at high
      voltages. We further demonstrate the correlation between electrode distance and
      current density during the anodic growth of TiO2 nanotubes and suggest that the
      change of current density regulated by electrode distance controls the growth of
      TiO2 nanotubes. The present study offers an effective approach to enhance the
      production of TiO2 nanotube arrays without changing the anodizing voltage and
      electrolyte composition and thus provides useful insights to the anodic growth of
      TiO2 nanotubes at reduced electrode distances.

PMID- 28453445
TI  - The effectiveness of a cognitive behavioral exercise approach (CBEA) compared to
      usual care in patients with a Whiplash Associated Disorder: A quasi-experimental
      clinical trial.
AB  - BACKGROUND: Whiplash Associated Disorders (WAD) is a biopsychosocial problem,
      education may be an essential part in the treatment and the prevention of chronic
      WAD. However, it is still unclear which type of educative intervention has
      already been used in WAD patients and how effective such interventions are.
      OBJECTIVE: To examine the effectiveness of a cognitive behavioral exercises
      approach (CBEA) for self-training of the neck relative to usual care in
      individuals with WAD in acute phase. METHODS: Forty-one patients, 65.9% female
      (mean +/- SD age: 41 +/-11 years), with WAD were recruited immediately after the
      accident (within 48 hours) and assigned according to patient choice to receive a
      CBEA self-training of the neck or usual care for 15 days. The primary outcome
      measure was pain intensity and disability as measured with the Neck Disability
      Index (NDI). Secondary outcome measures included the presence of headaches,
      dizziness, nausea, and difficulties with concentration and memory. Measurements
      were taken at pre-treatment, 2 weeks post-treatment and 4- and 12- weeks after
      the injury. RESULTS: Patients receiving the CBEA intervention experienced a
      greater reduction in pain as compared to those receiving the usual care at the
      end as well as 4 and 12 weeks after the intervention (P< 0.001), for the Neck
      Disability Index (NDI) decreased more in the CBEA than controls over the 15 days
      and (F=[3.0] 552.383; P= 0.001), and in both groups at all follow-up periods
      (all, P= 0.001). CONCLUSIONS: This quasi-experimental clinical trial provides
      evidence that a CBEA for self-training of the neck may be more beneficial in
      treating pain than usual care in patients with WAD. However, the CBEA had limited
      value in improving NDI. Future studies should include several therapists, a
      measure of a long-term outcomes and randomize patients to groups.

PMID- 28453446
TI  - The effects of neural mobilization on cervical radiculopathy patients' pain,
      disability, ROM, and deep flexor endurance.
AB  - BACKGROUND: Cervical radiculopathy (CR) is a disease of the cervical spine and a
      space-occupying lesion that occurs because of pathological problems with cervical
      nerve roots. Nerve root injury to produce functional disability. OBJECTIVE: The
      purpose of this study was to examine the effects of neural mobilization with
      manual cervical traction (NMCT) compared with manual cervical traction (MCT) on
      pain, functional disability, muscle endurance, and range of motion (ROM) in
      individuals with CR patients. METHODS: A blinded randomized clinical trial was
      conducted. Thirty CR patients were divided into two groups - those who received
      NMCT and those who received MCT. The intervention was applied three times per
      week for eight weeks. It was measured in order to determine the pain and
      functional disability in patients with CR. The numeric pain rating scale (NPRS),
      neck disability index (NDI), ROM, and deep flexor endurance of patients were
      measured prior to the experiment, four weeks, and eight weeks after the
      experiment to compare the time points. A repeated-measures analysis of variance
      was used to compare differences within each group prior to the experiment. And
      Bonferroni test was performed to examine the significance of each time point.
      RESULTS: There were significant differences within each group prior to the
      intervention, four weeks after the intervention, and eight weeks after the
      intervention in NPRS, NDI, ROM, and deep flexor endurance (P< 0.05). NPRS and NDI
      more decreased, and, ROM and deep flexor endurance increased in the NMCT group
      than the MCT group (P< 0.05). CONCLUSIONS: These results suggest that the NMCT
      can pain relief, recovery from neck disability, ROM, and deep flexor endurance
      for patients with CR.

PMID- 28453447
TI  - Correlation between forward head posture, respiratory functions, and respiratory
      accessory muscles in young adults.
AB  - BACKGROUND: Forward head posture (FHP) causes changes in the strengths and
      rigidities of cervical muscles. OBJECTIVE: The aim of this study was to
      investigate correlations between FHP and respiratory functions and the muscle
      activities of respiratory accessory muscles in young adults in their 20s.
      METHODS: A volunteer sample of 33 healthy young adults participated in this
      study. Craniovertebral angle (CVA), cranial rotational angle (CRA), vital
      capacity (VC), forced vital capacity (FVC), forced expiratory volume at 1 second
      (FEV1), peak expiratory flow (PEF), maximal voluntary ventilation (MVV), and
      sternocleidomastoid (SCM) and upper trapezius activity ratios were measured.
      RESULTS: Significant positive correlations were found between CVA and VC, FVC,
      FEV1, PEF, and MVV, and a significant negative correlation was found between CVA
      and SCM activity ratio. Significant negative correlations existed between CRA and
      VC and FVC, and significant positive correlations between CRA and SCM and upper
      trapezius activity ratios. CONCLUSION: FHP may act to lower respiratory
      functions, and thus, the maintenance of correct head posture is required to
      prevent such functional reductions.

PMID- 28453448
TI  - Cumulative trauma disorders: A review.
AB  - BACKGROUND: Cumulative trauma disorder (CTD) is a term for various injuries of
      the musculoskeletal and nervous systems that are caused by repetitive tasks,
      forceful exertions, vibrations, mechanical compression or sustained postures.
      Although there are many studies citing incidence of CTDs, there are fewer
      articles about its etiology, pathology and management. OBJECTIVE: The aim of our
      study was to discuss the etiology, pathogenesis, prevention and management of
      CTDs. METHODS: A literature search was performed using various electronic
      databases. The search was limited to articles in English language pertaining to
      randomized clinical trials, cohort studies and systematic reviews of CTDs.
      RESULTS: A total of 180 papers were identified to be relevant published since
      1959. Out of these, 125 papers reported about its incidence and 50 about its
      conservative treatment. CONCLUSIONS: Workplace environment, same task
      repeatability and little variability, decreased time for rest, increase in
      expectations are major factors for developing CTDs. Prevention of its etiology
      and early diagnosis can be the best to decrease its incidence and severity. For
      effective management of CTDs, its treatment should be divided into Primordial,
      Primary, Secondary and Tertiary prevention.

PMID- 28453449
TI  - Effect of upright and slouch sitting postures and voluntary teeth clenching on
      hand grip strength in young male adults.
AB  - BACKGROUND: Estimation of handgrip strength (HGS) is routinely used by clinicians
      and epidemiologists for objective assessment of functional status of hand and
      upper extremity. It is also used as an indirect indicator of overall physical
      strength and health status in variety of clinical situations and chronic general
      medical conditions. OBJECTIVE: The present study was conducted to examine the
      effects of upright and slouch sitting postures and voluntary teeth clenching on
      hand grip strength in healthy young male subjects. METHODS: One hundred healthy
      young males (aged 18-30 years) participated in this study. The HGS was measured
      using a commercially available dynamometer for the dominant hand. The HGS was
      measured during four test conditions; (a) slouch sitting without teeth contact,
      (b) slouch sitting with teeth clenching, (c) upright sitting without teeth
      contact, and (d) upright sitting with teeth clenching. RESULTS: The HGS values
      were significantly higher during slouch than upright sitting posture, both during
      similar and opposite teeth related conditions (p< 0.001). Teeth clenching had no
      effect on the in HGS values during slouch or upright sitting posture (P> 0.05).
      CONCLUSIONS: As compared to upright sitting, higher HGS values can be obtained
      during slouch sitting in young healthy males. Teeth clenching does not affect the
      HGS values during slouch or upright sitting posture.

PMID- 28453450
TI  - Muscle function and size in the lumbar spine before and after a four week
      exercise intervention.
AB  - BACKGROUND: Exercise of the spinal muscles is recommended for a variety of
      rehabilitative reasons but it is not always clear whether interventions are
      effective in improving the performance of the muscles or whether their benefit is
      elicited via other mechanisms. OBJECTIVE: To explore the effects of an exercise
      intervention on the size and exercise performance of the lumbar spine extensor
      muscles. METHODS: Eleven healthy participants undertook a four week programme of
      exercise. Magnetic resonance imaging and phosphorus spectroscopy were performed
      before and after the intervention to determine the time to fatigue and
      phosphocreatine (PCr) depletion during a muscle endurance test (modified Biering
      Sorensen) together with muscle cross-sectional area (CSA). RESULTS: The post
      intervention measures were significantly different to the pre-intervention
      results for the time to fatigue (post-pre: 20.5 +/- 22.7 s (P= 0.014)) and PCr
      depletion both at the point of fatigue (post-pre: 9.5 +/- 11.9% (P= 0.024)) and
      at a matched time-point (post-pre: 12.2 +/- 11.9% (P= 0.007)). CSA was not
      significantly different in any muscle. CONCLUSIONS: Exercise improved the
      performance of the trunk muscles despite no impact on CSA. This demonstrated the
      importance of obtaining a wide range of measures when assessing the effectiveness
      of exercise intervention programmes.

PMID- 28453451
TI  - Sensitivity for palpating lumbopelvic soft- tissues and bony landmarks and its
      associated factors: A single-blinded diagnostic accuracy study.
AB  - BACKGROUND: Evidence on the diagnostic performance of palpatory methods and
      possible confounding factors is scarce. OBJECTIVES: To examine the sensitivity of
      palpatory methods for location of lumbopelvic landmarks and to assess its
      association with personal characteristics. METHODS: Eighty-three participants (41
      men, 55.6 (16.5) years, 25.9 (4.8) kg/m2 [mean (SD)]) were enrolled in this
      single-blinded study. Fourteen body and softy-tissue landmarks were sequentially
      palpated from the spinous process of L4 to the ischial tuberosity. CT-scan images
      were used to assess what landmark was located. RESULTS: Sensitivity for location
      was in range 22-86% for soft-tissues and 26-69% for bony landmarks. Reduction in
      sensitivity was observed from the quadratus lumborum to the inferior and lateral
      angle of the sacrum (86-26% and 75-33%, left and right sides, respectively).
      Palpations of L4 and L5 spinous processes were systematically more cephalic than
      other landmarks. Gender was weakly correlated to almost all landmarks (rp?b=
      0.333 or weaker). Body mass index was weakly correlated to the accurate location
      of ILAS and quadratus lumborum, great trochanter, PSIS, and piriformis (rp?b=
      0.307 or weaker). CONCLUSIONS: Systematic and propagation errors were present
      using sequential palpatory methods. Palpation in men was more sensitive and
      higher BMI was associated with lower sensitivity for lumbopelvic landmarks.

PMID- 28453452
TI  - The efficacy of a HUBER exercise system mediated sensorimotor training protocol
      on proprioceptive system, lumbar movement control and quality of life in patients
      with chronic non-specific low back pain.
AB  - BACKGROUND: There is a relation between deficits of the proprioceptive system and
      movement control dysfunction in patients with chronic low back pain (LBP) but,
      the exact mechanism of this relation is unknown. Exercise therapy has been
      recognized as an effective method for low back pain treatment. In spite of this,
      it is not clear which of the various exercise therapy programs lead to better
      results. OBJECTIVE: Therefore, the present analyze the efficacy of a HUBER study
      aims to exercise system mediated sensorimotor training protocol on proprioceptive
      system, lumbar movement control (LMC) and quality of life (QOL) in patients with
      chronic non-specific LBP. DESIGN: Quasi-experimental study. METHODS: 53 patients
      with chronic non-specific LBP (mean age 37.55 +/- 6.67 years,and Body Mass Index
      (BMI) 22.4 +/- 3.33) were selected by using Roland-Morris Disability
      Questionnaire (RMQ) and were assigned into two experimental (N= 27) and control
      groups (N= 26) The experimental group underwent a five-week (10 sessions)
      Sensorimotor training by using the Human Body Equalizer (HUBER) spine force under
      the supervision of an investigator. The movement control battery tests, the HUBER
      machine testing option, goniometer and visual analogue scale used for movement
      control, neuromuscular coordination, proprioception and LBP assessment
      respectively. The assessments were completed in pre-test and after five weeks.
      The paired and sample T tests were used for data analysis in SPSS program version
      18 (Significance level were set at a P value < 0.05). RESULTS: The HUBER system
      mediated sensorimotor training demonstrated significant improvement in the
      proprioceptive system, LMC and QOL (P= 0.001). Also There was a significant
      reduction in the pain scores of subjects with chronic non-specific LBP in the
      sensorimotor group (P= 0.001). LIMITATIONS: In this study, only the short term
      effects of the sensorimotor training were examined. CONCLUSIONS: The results
      suggest that a sensorimotor training program causes significant improvement in
      patients with chronic non-specific LBP. Future research should be carried out
      with a larger sample size to examine the long term effects of the sensorimotor
      training program on treatment of patients with chronic non-specific LBP.
      Considering the efficacy of the sensorimotor training, it is recommended that
      this intervention should be applied to treatment of patients with chronic non
      specific LBP in the future.

PMID- 28453453
TI  - Whole body vibration versus magnetic therapy on bone mineral density in elderly
      osteoporotic individuals.
AB  - BACKGROUND: Osteoporosis usually develops gradually and progresses without
      significant signs and symptoms. It is one of the most common musculoskeletal
      conditions associated with aging. OBJECTIVES: To evaluate the effects of whole
      body vibration (WBV) or magnetic therapy in addition to standard pharmacological
      treatment on bone mineral density (BMD) in elderly individuals being treated for
      osteoporosis. METHODS: Eighty-five participants, 60-75 years of age, were
      randomly divided into three groups. All three groups received the same standard
      pharmacological treatment comprised of vitamin D, calcium, and alendronate
      sodium. In Group I, thirty participants were also exposed to WBV for 25 minutes
      in each session with two sessions per week for 4 months. In Group II, thirty
      participants were exposed to magnetic therapy for 50 minutes in each session with
      two sessions per week for 4 months. In Group III, twenty-five participants
      received only pharmacological treatment. Dual-energy X-ray absorptiometry was
      used to measure BMD of the lumbar spine and femoral heads before and after
      interventions. Venus blood sample was drawn for analysis of calcium and vitamin
      D. RESULTS: An ANOVA test detected significant (p< 0.05) differences in BMD after
      treatment among the three groups with no significant difference was detected
      between patients receiving WBV and magnetic therapy. Statistical t-tests detected
      significant (p< 0.05) increases in BMD after application of WBV or magnetic
      therapy in combination with pharmacological treatment, but no significant
      increase after pharmacological treatment alone. CONCLUSIONS: Addition of either
      WBV or magnetic therapy to standard pharmacological treatment for osteoporosis
      significantly increased BMD in elderly subjects. No significant difference in
      effectiveness was detected between these two alternative therapy modalities.
      Consequently, either WBV or magnetic therapy could be effectively applied in
      conjunction with pharmacological treatment to increase BMD in elderly
      osteoporotic patients.

PMID- 28453454
TI  - The effect of intra-articular hyaluronate and tramadol injection on patients with
      adhesive capsulitis of the shoulder.
AB  - BACKGROUND: Local administration of opioids causes effective analgesia without
      adverse effects related to the central nervous system. After the beneficial
      demonstration of peripheral opioid receptors in joint synovia, intra-articular
      opioid injections were used for pain treatment. Clinical studies have reported
      the safety and efficacy of hyaluronate injection in the shoulder joint of
      patients with osteoarthritis, periarthritis, rotator cuff tears, and adhesive
      capsulitis. OBJECTIVES: To estimate the efficacy of intra-articular hyaluronate
      and tramadol injection for adhesive capsulitis of the shoulder compared with that
      of intra-articular hyaluronate injection alone. METHODS: Thirty patients with
      adhesive capsulitis of the shoulder were randomized to the hyaluronate group (n=
      16) or the tramadol group (n= 14). Hyaluronate group members were administered
      five weekly intra-articular hyaluronate injections; tramadol group members were
      administered three weekly intra-articular hyaluronate and tramadol injections and
      then two weekly intra-articular injections of hyaluronate. Visual Analog Scale
      (VAS), passive range of motion (PROM) of the shoulder joint, and Shoulder Pain
      and Disability Index (SPADI) scores were assessed at baseline and weeks 1, 2, 3,
      4, and 6 after the initial injection. RESULTS: A significant improvement was
      observed in VAS, PROM, and SPADI scores between time points in both groups. In
      comparison in both groups at weeks 1 and 2 after the initial injection the VAS
      scores of the tramadol group were significantly lower than those of the
      hyaluronate group. CONCLUSIONS: Intra-articular hyaluronate with tramadol showed
      more rapid and strong analgesic effects than intra-articular hyaluronate alone
      and did not induce any adverse effects.

PMID- 28453455
TI  - Spinal cord injury in elderly patients admitted to a tertiary hospital.
AB  - BACKGROUND: Spinal cord injury (SCI) has a negative impact on quality of life and
      healthcare costs. In recent years with the age pyramid inversion, there has been
      a high prevalence of SCI in the elderly. These patients must be studied in order
      to invest in the prevention and treatment of SCI in these patients. OBJECTIVE: To
      identify the characteristics and clinical aspects of spinal cord injury (SCI) in
      the elderly. METHODS: Retrospective study of elderly patients (>= 60 years of
      age) with a clinical diagnosis of SCI. Clinical and socio-demographic variables
      were collected from medical records. RESULTS: Sixty-two elderly patients were
      studied (56% men). The patients were analyzed according to gender. Women
      presented compression fractures associated with thoracolumbar transition, while
      men presented with listhesis associated with cervical lesions and increased
      complications. It was found that the need for surgical intervention was higher in
      men. Among many characteristics that differed between the elderly and younger
      people (< 60 years; n = 259), in the morphological diagnosis, we observed that
      compression fractures and dislocation fractures were more highly associated with
      ages >= 60 and < 60, respectively. After SCI, the elderly have a higher risk for
      late hemodynamic instability. CONCLUSION: Elderly individuals with SCI have
      distinct characteristics and clinical factors related to gender and age.

PMID- 28453456
TI  - The synergic effect of HPV infection and epigenetic anomaly of the p16 gene in
      the development of cervical cancer.
AB  - BACKGROUND: Cervical cancer is the most common cancer in Indian women. Infection
      with a high-risk human papillomavirus (HR-HPV) is the greatest risk factor for
      developing cervical cancer. The genetic and epigenetic changes in the tumor
      suppressor p16 gene is play an important role in the development of cervical
      cancer. OBJECTIVE: To evaluate the expression and promoter methylation of p16
      gene in HR-HPV infected squamous cell carcinoma of the uterine cervix. METHODS:
      To find out p16INK4a expression and methylation status 105 squamous cell
      carcinoma of the uterine cervix were investigated by using immunohistochemistry
      and Methylation Specific PCR techniques. RESULTS: HPV16/18 was amplified in 83.8%
      cases of the cervix. 80% of them were positive for HPV type 16, while only 3.8%
      were positive for HPV type 18. Promoter CpG island hypermethylation of p16 gene
      was detected in 20.9% tissue samples of cervical carcinoma. Of these
      hypermethylated samples 90.9% cases showed nil/very low p16INK4a expression (P=
      0.001). Overexpression of p16INK4a was observed in 73.3% cases of HR-HPV infected
      squamous cell carcinoma of the cervix. CONCLUSION: An association between p16
      methylation, expression, and HR-HPV infection suggested the compliance of HPV
      infection and aberration of p16 gene have a synergic effect on initiation and
      progression of cervical carcinoma.

PMID- 28453457
TI  - Plasma expression of the intestinal metaplasia markers CDH17 and TFF3 in patients
      with gastric cancer.
AB  - BACKGROUND: Few reliable blood markers are available for detecting gastric
      cancer, mainly owing to the heterogeneity of the cancer. OBJECTIVE: To establish
      gastric cancer diagnostic markers, we evaluated the levels of plasma cadherin 17
      (CDH17) and trefoil factor 3 (TFF3), which are secretory proteins and known
      markers for intestinal metaplasia (IM), in patients with gastric cancer. METHOD:
      The protein expression level was analyzed in blood plasma samples from 111
      gastric cancer patients and 44 healthy individuals, using a sandwich ELISA kit,
      followed by statistical analyses. RESULT: Overall, the plasma levels of CDH17 and
      TFF3 were not significantly different between groups (p= 0.160 and p= 0.113,
      respectively). However, CDH17 expression was significantly elevated in patients
      with stage II and III gastric cancers compared to that in healthy controls (p=
      0.023 and p= 0.037, respectively). In contrast, TFF3 levels were significantly
      elevated in patients with stage I (p= 0.001) and T1 gastric cancer (p= 0.013).
      The sensitivity and specificity of CDH17 were 66.7 and 61.4%, respectively
      (cutoff point: 0.189 ng/mL); for TFF3, these values were 62.2 and 56.8%,
      respectively (cutoff point: 5.215 ng/mL). CONCLUSIONS: These findings indicate
      that secretory protein markers for metaplastic lineages can be used as blood
      markers for gastric cancer.

PMID- 28453458
TI  - Reduced EphB6 protein in gastric carcinoma and associated lymph nodes suggests
      EphB6 as a gastric tumor and metastasis inhibitor.
AB  - BACKGROUND: Eph receptors comprise the largest group of the receptor tyrosine
      kinase (RTK) family, and Eph receptors interacting with their ligand ephrins play
      an important role in development and tumorigenesis. EphB6, a special Eph receptor
      that lacks tyrosine kinase activity, was reported to be expressed in some human
      cancers. The clinical significance of EphB6 in gastric carcinoma has not been
      well investigated. METHODS: In this study, we detected expression of EphB6
      protein in four gastric cancer cell lines and a set of gastric carcinoma tissue
      specimens by using immunohistochemistry. The relationship between EphB6 protein
      expression and clinicopathological parameters was statistically analyzed.
      RESULTS: EphB6 protein was differentially detected in four gastric cancer cell
      lines. EphB6 protein was low expressed in 52.6%, moderately expressed in 32.59%,
      and strongly expressed in 14.5% of gastric carcinomas. EphB6 expression was
      positively associated with tumor differentiation (P< 0.001, rs= 0.476), and
      negatively associated with lymph node metastasis (P< 0.001, rs=-0.444) and tumor
      stage (P= 0.001, rs=-0.269). Low EphB6 expression was detected more often in
      female patients (P= 0.031). No significant relationship between EphB6 expression
      and patient age, tumor location, or depth of tumor invasion was identified.
      CONCLUSION: Our data indicate that EphB6 protein was decreased in gastric
      carcinoma compared with normal mucosa. Analytic results based on pathological
      parameters suggests that EphB6 protein may inhibit metastasis of gastric
      carcinoma and could be a potential therapeutic target for gastric carcinoma.

PMID- 28453459
TI  - Evaluation of short-term and long-term efficacy of surgical and non-surgical
      treatment in patients with early-stage small cell lung cancer: A comparative
      study.
AB  - OBJECTIVE: The aim of this study is to compare surgery with adjuvant
      chemoradiotherapy versus non-surgical treatments for patients with early-stage
      small cell lung cancer (SCLC) based on the short-term and long-term efficacy.
      METHODS: SCLC patients who underwent a pulmonary lobectomy with post-surgical
      radiotherapy or chemotherapy were assigned to the surgical group. SCLC patients
      who received radiotherapy or chemotherapy alone were classified into the non
      surgical group. The clinical efficacy was evaluated as complete remission (CR),
      partial remission (PR), stable disease (SD), or progressive disease (PD). The
      total effectiveness rate was calculated as CR + PR. The 1-, 3-, and 5-year
      survival rates of the two groups were compared. RESULTS: Compared with the non
      surgical group, the CR rate and the total effectiveness rate were higher in the
      surgical group, and the total effectiveness rate for male patients and patients
      without a smoking history were also higher in the surgical group. Distant
      metastasis and local recurrence concurrent with distant metastasis in the
      surgical group were both lower in the surgical group than in the non-surgical
      group. Compared with the non-surgical group, the local recurrence in male
      patients was lower in the surgical group, and patients in the surgical group had
      lower distant metastasis at TNM stage IIb. The 1-, 3-, and 5-year survival rates
      were higher in the surgical group than in the non-surgical group. CONCLUSIONS:
      These findings indicate that for patients with early-stage SCLC, better scores in
      effectiveness rate, disease progression, and 1-, 3-, and 5-year survival rates
      were observed in patients who underwent surgery followed by adjuvant
      chemoradiotherapy when compared with patients without surgical treatment.

PMID- 28453460
TI  - Endoplasmic reticulum stress regulates proliferation, migration and invasion of
      human ovarian cancer SKOV3 cells through PI3K/AKT/mTOR signaling pathway.
AB  - OBJECTIVE: The study is to explore the role of tunicamycin-induced endoplasmic
      reticulum stress (ERS) in human ovarian cancer (OC) SKOV3 cells proliferation,
      migration and invasion by modulating the activity of PI3K/AKT/mTOR pathway.
      METHODS: The collected human OC SKOV3 cells were randomly separated into three
      groups: The control group, the Tun group (treated with tunicamycin to induce ERS)
      and the CHOP-si group (transfected with CHOP-siRNA before tunicamycin treatment).
      CCK-8 method was applied for testing cell proliferation, while flow cytometry was
      conducted to detect cell apoptosis. Scratch test and Transwell test were used to
      determine the level of cell migration and invasion, respectively. Western
      blotting was performed to determine the related proteins expressions in ERS and
      PI3K/AKT/mTOR pathway. RESULTS: The cell survival rate in the Tun group was
      enhanced than that in the CHOP-si group, both of which were declined with the
      passage of time. The cell apoptosis rate in the Tun group was increased compared
      to the CHOP-si group, both of which were significantly elevated. The horizontal
      migration distance and the number of invasive cells in the Tun and CHOP-si groups
      were inhibited; however, the horizontal migration distance and the number of
      invasive cells in the CHOP-si group were enhanced than that in the Tun group. In
      comparison with the control group, the expressions of CHOP and TRB3 were
      increased in the Tun group but decreased in the CHOP-si group. The PI3K, p-AKT
      and p-mTOR expressions were remarkably declined in the Tun group than those in
      the control group (P< 0.05). CONCLUSION: The study provides strong evidence that
      tunicamycin-induced ERS induces the apoptosis of human OC SKOV3 cells through
      inhibiting PI3K/AKT/mTOR signaling pathway.

PMID- 28453461
TI  - SerpinE2, a poor biomarker of endometrial cancer, promotes the proliferation and
      mobility of EC cells.
AB  - The SerpinE2 pathway is evolutionarily conserved and plays an important role in
      tumorigenesis. SerpinE2 (a small ubiquitin-related modifier), like ubiquitin,
      conjugates SerpinE2 proteins onto lysine residues of target proteins. SerpinE2
      over-expression has been found in several tumors. Here, we detected the level of
      SerpinE2 in 72 samples of EC tissue using immunohistochemistry to assess the role
      of SerpinE2 in EC prognosis. Meanwhile, we knocked down SerpinE2 by siRNA in the
      HTB-111 and Ishikawa EC cell lines and analyzed the viability and mobility change
      using an MTT assay, an annexin V/PI apoptosis assay, a wound scratch test and a
      transwell assay. A Kaplan-Meier analysis indicated a negative correlation between
      the level of SerpinE2 and the EC prognosis. Silencing SerpinE2 induced cell
      apoptosis and reduced the migration ability. Our data suggest SerpinE2 works as
      an oncogene in EC.

PMID- 28453462
TI  - Up-regulated miR-221 expression as a molecular diagnostic marker in laryngeal
      squamous cell carcinoma and its correlation with Apaf-1 expression.
AB  - BACKGROUND: Despite the improvement in the diagnosis and the management of
      laryngeal squamous cell carcinoma (LSCC), many patients with advanced-stage have
      poor prognosis in the form of recurrence, metastasis or death. So, recognition of
      new molecular markers would facilitate the development of targeted therapies.
      OBJECTIVES: To investigate miR-221 expression in LSCC and its possible
      correlation to apoptotic protease activating factor-1 (Apaf-1). Also, we aimed to
      investigate the association between miR-221 and Apaf-1 expressions and the
      clinicopathological features of LSCC. METHODS: We investigated the expression of
      miR-221 (by qRT-PCR) and Apaf-1 (by qRT-PCR and immunohistochemistry) in primary
      LSCC and adjacent normal tissues. RESULTS: We found significant up-regulation of
      miR-221 and significant down-regulation of Apaf-1 expression in LSCC tissues
      compared to normal nearby laryngeal tissues. In addition, significant
      associations between up-regulated miR-221 and down-regulated Apaf-1 expressions
      and clinical stage and lymph node (LN) metastasis (P< 0.001 for each) were found.
      Furthermore, there was a negative correlation between miR-221 gene expression and
      Apaf-1 gene expression (r=-0.73, P< 0.001). CONCLUSION: miR-221 can be considered
      as a diagnostic marker in LSCC and Apaf-1 may be considered as a possible target
      of miR-221.

PMID- 28453463
TI  - The IGF-I/JAK2-STAT3/miR-21 signaling pathway may be associated with human renal
      cell carcinoma cell growth.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is the highest mortality rate of the
      genitourinary cancers, and the treatment options are very limited. Thus,
      identification of molecular mechanisms underlying RCC tumorigenesis, is critical
      for identifying biomarkers for RCC diagnosis and prognosis. OBJECTIVE: To
      validate whether the IGF-I/JAK2-STAT3/miR-21 signaling pathway is associated with
      human RCC cell growth. METHODS: qRT-PCR and Western blotting were used to detect
      the mRNA and protein expression levels, respectively. The MTT assay was performed
      to determine cell survival rate. The Annexin V-FITC/PI apoptosis detection kit
      was used to detect cell apoptosis. We employed RCC tissues and cell lines (A498;
      ACHN; Caki-1; Caki-2 and 786-O) in the study. IGF-I, and its inhibitor (NT-157)
      were administrated to detect the effects of IGF-I on the expression of miR-21 and
      p-JAK2. JAK2 inhibitor (AG490), and si-STAT3 were used to detect the effects of
      JAK2/STAT3 signaling pathway on the expression of miR-21. RESULTS: In our study,
      we firstly showed that the expression levels of IGF-I and miR-21 were up
      regulated in RCC tissues and cell lines. After exogenous IGF-I treatment, the
      expression levels of miR-21, p-IGF-IR and p-JAK2 were significantly increased,
      whereas NT-157 treatment showed the reversed results. Further study indicated
      that JAK2 inhibitor or si-STAT3 significantly reversed the IGF-I-induced miR-21
      expression level. Finally, we found that IGF-I treatment significantly prompted
      human RCC cell survival and inhibited cell apoptosis, and NT-157 treatment showed
      the reversed results. CONCLUSIONS: The IGF-I/JAK2-STAT3/miR-21 signaling pathway
      may be associated with human RCC cell growth.

PMID- 28453464
TI  - PPARGC1A and ADIPOQ polymorphisms are associated with aggressive prostate cancer
      in Mexican-Mestizo men with overweight or obesity.
AB  - BACKGROUND: Obesity constitutes a risk factor for the development of aggressive
      forms of prostate cancer. It has been proposed, that prostate cancer has a
      genetic predisposition and that PPARGC1A and ADIPOQ polymorphisms play a role in
      the development of this condition. OBJECTIVE: To analyse the association of two
      PPARGC1A and ADIPOQ polymorphisms as well as their haplotypes, with the
      development of aggressive prostate cancer in Mexican-Mestizo men with overweight
      or obesity. SUBJECTS AND METHODS: Two hundred fifty seven men with prostate
      cancer of Mexican-Mestizo origin were included. Body mass index (BMI) was
      determined and the degree of prostate cancer aggressiveness by the D'Amico
      classification. DNA was obtained. Rs7665116 and rs2970870 of PPARGC1A, and
      rs266729 and rs1501299 of ADIPOQ were studied by real-time PCR allelic
      discrimination. Pairwise linkage disequilibrium, between single nucleotide
      polymorphisms was calculated and haplotype analysis was performed. RESULTS: A
      higher-risk (D'Amico classification) was observed in 21.8% of patients. An
      association of cancer aggressiveness with rs2970870 of PPARGC1A, and rs501299 of
      ADIPOQ, as well as with one haplotype of ADIPOQ was documented. CONCLUSIONS: This
      is the first study regarding the relationship of PPARGC1A and ADIPOQ
      polymorphisms, and the aggressiveness of prostate cancer in men with overweight
      or obesity.

PMID- 28453465
TI  - High expression of LAMP2 predicts poor prognosis in patients with esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: LAMP2 is one of the major protein components of lysosome. In addition
      to the expression on the lysosomal membrane, LAMP2 has also been found
      relocalizing to the cell surface of some highly metastatic tumor cells.
      OBJECTIVE: The aim of this study was to detect the expression levels of LAMP2 and
      discuss its roles in esophageal squamous cell carcinoma (ESCC). METHODS: Six
      hundred and ten tissue samples of ESCC were collected to construct tissue
      microarrays, which were stained by immunohistochemistry. RESULTS: After
      immunohistochemical staining, 596 patients including 460 men and 136 women were
      analyzed. The LAMP2 expression levels were significantly different based on
      degrees of histological differentiation (chi2= 108.906, P< 0.001). The similar
      results were also observed in TNM stages (chi2= 23.835, P< 0.01). LAMP2
      expression levels negatively correlated with degrees of histological
      differentiation (P< 0.01). Logistic regression analysis showed that the LAMP2
      expression levels were correlated with the degrees of histological
      differentiation (OR=?????????????????????????????? 0.452, P< 0.001) and TNM
      stages (OR=?????? 1.482, P= 0.42). Besides, Kaplan-Meier survival curves
      indicated that patients with higher expression of LAMP2 exhibited poor prognosis
      (P< 0.05). CONCLUSIONS: Our results demonstrated that LAMP2 expression levels
      correlated with tumor histological differentiation and TNM stages. High
      expression of LAMP2 predicts poor prognosis in patients with ESCC.

PMID- 28453466
TI  - Clinicopathological and prognostic significance of GPx2 protein expression in
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: This study was designed to evaluate the relation between GPx2
      (glutathione peroxidase 2) expressions and clinicopathological features as well
      as prognosis of patients with nasopharyngeal carcinoma (NPC). METHODS: A total of
      89 cases of NPC were investigated to examine the immunohistochemical expression
      of GPx2. Fourteen pairs of NPC and the control samples were analyzed respectively
      by qRT-PCR and Western blot. The correlations of GPx2 expressions with the
      clinicopathologic features and the prognosis of NPC patients were also analyzed.
      RESULTS: The expression of GPx2 in NPC tissues was elevated immunohistochemically
      when compared with normal nasopharyngeal tissues (P< 0.05). The mRNA expression
      of GPx2 in carcinoma tissues was highly elevated compared with the control
      tissues (P< 0.05). GPx2 protein in carcinoma tissues was also over expressed than
      in control tissues (P< 0.05). Also GPx2 expression was significantly higher in
      the late clinical stage (P= 0.02). While there was no significant association
      between GPx2 expression and patient age, sex, T-stage, N-stage and the
      metastasis. CONCLUSIONS: GPx2 may play an important role in the development of
      nasopharyngeal carcinoma. Furthermore, GPx2 may serve as a prognostic biomarker
      for NPC patient.

PMID- 28453467
TI  - Prognostic significance of MYCN gene amplification and protein expression in
      primary brain tumors: Astrocytoma and meningioma.
AB  - BACKGROUND: Astrocytoma and meningioma are the most common primary brain tumors.
      MYCN as a member of MYC proto-oncogenes has recently appeared as an attractive
      therapeutic target. Functions of MYCN are critical for growth of nervous system
      and neural differentiation. OBJECTIVE: We examined MYCN amplification and protein
      expression in astrocytoma and meningioma cases. METHODS: In this study, we used
      real-time PCR, FISH assay and flowcytometry to analyze DNA amplification and
      protein expression of MYCN. RESULTS: Among 30 samples of brain tumor, 14 cases
      (46.6%) revealed MYCN amplification. High-protein expression of MYCN was also
      observed in 43.3% of patients. There was a significant correlation between MYCN
      gene amplification and protein expression (r= 0.523; p= 0.003), interestingly
      five case showed discrepancy between the gene amplification and protein
      expression. Although MYCN amplification fails to show correlation with poor
      prognosis (p= 0.305), protein high-expression of MYCN significantly reduce
      disease-free survival (p= 0.019). CONCLUSIONS: Our results challenge the concept
      of the neural specificity of MYCN by demonstrating contribution of MYCN in
      meningioma. Moreover, this study highlights the importance of research at both
      level of DNA and protein, to determine the biological functions and medical
      impacts of MYCN.

PMID- 28453469
TI  - Use of Analgesics (Opioids and Nonsteroidal Anti-Inflammatory Drugs) and Dementia
      Related Neuropathology in a Community-Based Autopsy Cohort.
AB  - BACKGROUND: Opioids may influence the development of Alzheimer's disease (AD).
      Some studies have observed AD pathology in the brains of opioid abusers. No study
      has examined the association between prescription opioid use and dementia-related
      neuropathologic changes. OBJECTIVE: To examine the relationship between
      prescription opioid or NSAID use and dementia-related neuropathologic changes.
      METHODS: Within a community-based autopsy cohort (N = 420), we ascertained opioid
      and nonsteroidal anti-inflammatory drug (NSAID) use over a 10-year period from
      automated pharmacy data and calculated total standardized daily doses (TSDDs). A
      neuropathologist assessed outcomes including neuritic plaques, neurofibrillary
      tangles, and macroscopic infarcts. Outcome measures were dichotomized using
      established cutpoints. We used modified Poisson regression to calculate adjusted
      relative risks (RR) and 95% confidence intervals (CI), accounting for participant
      characteristics and using weighting to account for possible selection bias
      related to selection into the autopsy sample. RESULTS: Heavier opioid exposure
      was not associated with greater neuropathologic changes. For neuritic plaques,
      the adjusted RR [95% CI] was 0.99 [0.64-1.47] for 91+ TSDDs of opioids versus
      little to no use, and for neurofibrillary tangles, 0.97 [0.49-1.78]. People with
      heavy NSAID use had higher risk of neuritic plaques (RR 1.39 [1.01-1.89]) than
      those with little to no use, as we have previously reported. Neither opioid nor
      NSAID use was associated with higher risk of macroscopic infarcts or with Lewy
      body disease. CONCLUSION: Prescription opioid use is not associated with dementia
      related neuropathologic changes, but heavy NSAID use may be. More research is
      needed examining chronic pain, its pharmacologic treatments, and neuropathologic
      changes.

PMID- 28453470
TI  - Three-Repeat Tau with Grain-Like Structures and Distribution in an 83-Year-Old
      Man.
AB  - We encountered an 83-year-old man with 3-repeat dominant grain-like tau
      deposition. Tau-positive lesions exhibited apparent similarity to argyrophilic
      grains in terms of their distribution in the ambient gyrus, amygdala, and
      dorsomedial temporal tip and the characteristic comma-like morphology. The
      abundant oligodendroglial tau immunoreactivities were 3-repeat dominant. Tuft
      shaped astrocytes showed partial 3-repeat tau immnoreactivities. These grain-like
      structures, as well as tuft-shaped astrocytes and oligodendroglia, exhibited
      predominant 3-repeat tau immunoreactivity, suggesting that grain-like structures
      and their characteristic distribution are mutually linked and not unique to 4
      repeat tau deposition. pTDP immunoreactivity, extensive macrophage infiltration,
      and spongiosis were associated with these 3-repeat tau deposits.

PMID- 28453471
TI  - A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005
      (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.
AB  - BACKGROUND: ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been
      evaluated as a potential disease-modifying treatment for Alzheimer's disease
      (AD). Individuals with Down syndrome (DS) have an increased risk for developing
      AD dementia. OBJECTIVE: To evaluate the safety and tolerability of ELND005 and to
      determine its pharmacokinetics (PK) and relationship between PK parameters,
      safety outcome measures, and exploratory efficacy outcome measures in young
      adults with DS without dementia. METHODS: This was a prospective, randomized,
      double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II
      study of the safety and pharmacokinetics of ELND005 administered orally for 4
      weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility
      criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either
      250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4
      weeks. RESULTS: There were no apparent treatment group-related trends on
      cognitive or behavioral measures and there were no SAEs and no deaths in the
      study. Overall, mean changes from baseline in clinical laboratory parameters,
      vital sign measurements, electrocardiogram results, and other physical findings
      were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD
      dosing, and 3- to 4-fold with BID dosing. CONCLUSION: Overall, treatment of
      adults with DS with ELND005 at both doses was well tolerated, achieved measurable
      blood levels and demonstrated no safety findings. Further studies will be needed
      to test efficacy.

PMID- 28453472
TI  - The 2002 NIMH Provisional Diagnostic Criteria for Depression of Alzheimer's
      Disease (PDC-dAD): Gauging their Validity over a Decade Later.
AB  - Presented herein is evidence for criterion, content, and convergent/discriminant
      validity of the NIMH-Provisional Diagnostic Criteria for depression of
      Alzheimer's Disease (PDC-dAD) that were formulated to address depression in
      Alzheimer's disease (AD). Using meta-analytic and systematic review methods, we
      examined criterion validity evidence in epidemiological and clinical studies
      comparing the PDC-dAD to Diagnostic and Statistical Manual of Mental Disorders
      fourth edition (DSM-IV), and International Classification of Disease (ICD 9)
      depression diagnostic criteria. We estimated prevalence of depression by PDC,
      DSM, and ICD with an omnibus event rate effect-size. We also examined diagnostic
      agreement between PDC and DSM. To gauge content validity, we reviewed rates of
      symptom endorsement for each diagnostic approach. Finally, we examined the PDC's
      relationship with assessment scales (global cognition, neuropsychiatric, and
      depression definition) for convergent validity evidence. The aggregate evidence
      supports the validity of the PDC-dAD. Our findings suggest that depression in AD
      differs from other depressive disorders including Major Depressive Disorder (MDD)
      in that dAD is more prevalent, with generally a milder presentation and with
      unique features not captured by the DSM. Although the PDC are the current
      standard for diagnosis of depression in AD, we identified the need for their
      further optimization based on predictive validity evidence.

PMID- 28453473
TI  - Prodromal Dementia with Lewy Bodies and Prodromal Alzheimer's Disease: A
      Comparison of the Cognitive and Clinical Profiles.
AB  - BACKGROUND: Dementia must be diagnosed accurately and early in the disease course
      to allow pathology-specific treatments to be effective. Dementia with Lewy bodies
      (DLB) is often misdiagnosed as Alzheimer's disease (AD), especially at the
      prodromal stage. OBJECTIVE: To compare the clinical and neuropsychological
      profiles of Mild Cognitive Impairment (MCI) patients who, at follow-up,
      progressed to AD (retrospectively AD-MCI) or DLB (retrospectively DLB-MCI) or
      remained MCI. METHODS: This longitudinal study used an unselected sample from a
      memory clinic database. A total of 1,848 new patients were seen at the memory
      clinic between 1994-2015. Of these, 560 patients (30%) had an initial diagnosis
      of MCI and were considered for the study. Inclusion criteria were patients who
      had a diagnosis of MCI at initial assessment and a minimum of 12 months' follow
      up. RESULTS: Of the 429 MCI patients with follow-up data, 164 (38%) remained MCI,
      107 (25%) progressed to AD, and 21 (5%) progressed to DLB. The remainder
      progressed to alternative diagnoses. At baseline, DLB-MCI patients performed
      significantly worse on visuospatial function and letter fluency tests than both
      AD-MCI and stable-MCI groups, and better on episodic memory tests than the AD-MCI
      group. At baseline, DLB-MCI patients had a significantly higher mean UPDRS score
      and were more likely to have REM sleep behavior disorder and fluctuating
      cognition. CONCLUSION: DLB-MCI patients have a specific cognitive and
      neuropsychiatric profile which should alert clinicians to the possibility of
      prodromal DLB. This is relevant when considered in the context of early disease
      specific therapy.

PMID- 28453474
TI  - Neuropsychological Profile in the C9ORF72 Associated Behavioral Variant
      Frontotemporal Dementia.
AB  - While the C9ORF72 expansion is a major cause of behavioral variant frontotemporal
      dementia (bvFTD), little is known of the resultant cognitive profile. Our aim was
      to characterize the neuropsychological profile of the C9ORF72 associated bvFTD.
      We contrasted structured neuropsychological assessments of the C9ORF72 expansion
      carrier bvFTD patients (n = 26) with non-carrier bvFTD patients (n = 47) and
      those with Alzheimer's disease (AD) (n = 47). As compared to the non-carrier
      bvFTD patients, the C9ORF72 expansion carriers performed at a higher level in an
      immediate verbal memory test while showing poorer phonemic verbal fluency.
      Additionally, the expansion carriers committed more errors in the Stroop test and
      the Alternating S task relative to the non-carriers. Finally, while the AD
      patients outperformed both bvFTD patient groups in working memory, their
      performance was more impaired in episodic memory tasks relative to the bvFTD
      groups. We conclude that bvFTD patients carrying the C9ORF72 expansion may
      display more pronounced executive deficits together with less severe verbal
      memory impairment as compared to their non-carrier bvFTD counterparts. Knowledge
      of the specific neuropsychological features associated with the C9ORF72 related
      bvFTD may aid in the early diagnosis of the disease as well as in targeting
      genetic testing.

PMID- 28453475
TI  - Modifiable Risk Factors for Prevention of Dementia in Midlife, Late Life and the
      Oldest-Old: Validation of the LIBRA Index.
AB  - BACKGROUND: Recently, the LIfestyle for BRAin health (LIBRA) index was developed
      to assess an individual's prevention potential for dementia. OBJECTIVE: We
      investigated the predictive validity of the LIBRA index for incident dementia in
      midlife, late life, and the oldest-old. METHODS: 9,387 non-demented individuals
      were recruited from the European population-based DESCRIPA study. An individual's
      LIBRA index was calculated solely based on modifiable risk factors: depression,
      diabetes, physical activity, hypertension, obesity, smoking,
      hypercholesterolemia, coronary heart disease, and mild/moderate alcohol use. Cox
      regression was used to test the predictive validity of LIBRA for dementia at
      follow-up (mean 7.2 y, range 1-16). RESULTS: In midlife (55-69 y, n = 3,256) and
      late life (70-79 y, n = 4,320), the risk for dementia increased with higher LIBRA
      scores. Individuals in the intermediate- and high-risk groups had a higher risk
      of dementia than those in the low-risk group. In the oldest-old (80-97 y, n =
      1,811), higher LIBRA scores did not increase the risk for dementia. CONCLUSION:
      LIBRA might be a useful tool to identify individuals for primary prevention
      interventions of dementia in midlife, and maybe in late life, but not in the
      oldest-old.

PMID- 28453477
TI  - Diagnostic Biomarkers of Alzheimer's Disease as Identified in Saliva using 1H NMR
      Based Metabolomics.
AB  - Using 1H NMR metabolomics, we biochemically profiled saliva samples collected
      from healthy-controls (n = 12), mild cognitive impairment (MCI) sufferers (n =
      8), and Alzheimer's disease (AD) patients (n = 9). We accurately identified
      significant concentration changes in 22 metabolites in the saliva of MCI and AD
      patients compared to controls. This pilot study demonstrates the potential for
      using metabolomics and saliva for the early diagnosis of AD. Given the ease and
      convenience of collecting saliva, the development of accurate and sensitive
      salivary biomarkers would be ideal for screening those at greatest risk of
      developing AD.

PMID- 28453476
TI  - Reduced Cerebral Blood Flow in Mild Cognitive Impairment Assessed Using Phase
      Contrast MRI.
AB  - There is increasing evidence of a vascular contribution to Alzheimer's disease
      (AD). In some cases, prior work suggests that chronic brain hypoperfusion could
      play a prime pathogenic role contributing to the accumulation of amyloid
      beta,while other studies favor the hypothesis that vascular dysfunction and
      amyloid pathology are independent, although synergistic, mechanisms contributing
      to cognitive impairment. Vascular dysfunction can be evaluated by assessing
      cerebral blood flow impairment. Phase contrast velocity mapping by MRI offers a
      non-invasive means of quantifying the total inflow of blood to the brain. This
      quantitative parameter could be a sensitive indicator of vascular disease at
      early stages of AD. In this work, phase contrast MRI was used to evaluate
      cerebral hemodynamics in patients with subjective memory complaints, amnestic
      mild cognitive impairment, and mild to moderate AD, and compare them with control
      subjects. Results showed that blood flow and velocity were decreased in the
      patients with cognitive dysfunction and the decrease correlated with the degree
      of cognitive impairment as assessed by means of neuropsychological tests. Total
      cerebral blood flow measurements were clearly reduced in AD patients, but more
      importantly appeared to be sensitive enough to distinguish between healthy
      subjects and those with mild cognitive impairment. A quantitative measurement of
      total brain blood flow could potentially predict vascular dysfunction and
      compromised brain perfusion in early stages of AD.

PMID- 28453478
TI  - Functional Reserve: Experience Participating in Instrumental Activities of Daily
      Living is Associated with Gender and Functional Independence in Mild Cognitive
      Impairment.
AB  - BACKGROUND: Gender differences in instrumental activities of daily living (IADLs)
      in mild cognitive impairment (MCI) and Alzheimer's disease may be explained by
      gender differences in IADL involvement. OBJECTIVE: We introduce a novel
      theoretical construct, termed functional reserve, and empirically examine gender
      differences in IADL experience as a proxy of this reserve. METHODS: We cross
      sectionally examined men (n = 502) and women (n = 340) with MCI from the
      Alzheimer's Disease Neuroimaging Initiative (ADNI). Demographic factors,
      depressive symptoms, neuropsychological scores, and IADL experience were included
      as independent variables and total Functional Activities Questionnaire (FAQ)
      scores as the dependent variable. Regression analyses were performed on the full
      cohort and stratified by gender to identify differential predictive relationships
      for men and women. RESULTS: Gender was associated with total FAQ (p < 0.05) until
      adjusting for IADL experience. Furthermore, the combination of cognitive measures
      accounted for the most variance in functional dependence (12% explained, p <
      0.001), although IADL experience was the most important single variable (4.8%
      explained, p < 0.001). Stratification by gender revealed that IADL experience
      accounted for 6.6% of the variance in FAQ score in men (p < 0.001) but only 2.4%
      in women (p = 0.001); however, the interaction between gender and experience was
      not statistically significant. DISCUSSION: A small effect of men showing greater
      functional dependence in MCI may be explained by lower IADL experience.
      Additionally, IADL experience was associated with superior functioning in all
      analyses, potentially through increased functional reserve. This concept of
      functional reserve may have implications for identifying individuals at risk for
      IADL dependence, preventing or delaying decline, and potentially treating
      functional impairment.

PMID- 28453479
TI  - Cognitive Domain Dispersion Association with Alzheimer's Disease Pathology.
AB  - Within neuropsychology, the term dispersion refers to the degree of variation in
      performance between different cognitive domains for an individual. Previous
      studies have demonstrated that cognitively normal individuals with higher
      dispersion are at an increased risk for progressing to mild cognitive impairment
      (MCI) and Alzheimer's disease (AD). Therefore, we determined 1) whether increased
      dispersion in older adults was associated with amyloid plaques and
      neurofibrillary tangles (NFTs) and 2) whether increased cognitive dispersion
      accurately differentiated MCI and AD from non-cognitively impaired (NCI)
      individuals. The intra-subject standard deviation (ISD) was used to quantify
      cognitive dispersion, and receiver operator characteristic (ROC) analysis
      determined whether ISD differentiated MCI and AD from NCI. Neuropathological
      scores for diffuse plaques (DPs), neuritic plaques (NPs), and NFTs were used as
      outcome measures in a series of negative binomial regression models. Regression
      analyses found that increased ISD was associated with increased NFT pathology
      (beta= 10.93, SE = 3.82, p = 0.004), but not with DPs (beta= 1.33, SE = 8.85, p =
      0.88) or NPs (beta= 14.64, SE = 8.45, p = 0.08) after adjusting for age at death,
      gender, education, APOE E4 status, and clinical diagnosis. An interaction term of
      ISD with age at death also showed a significant negative association (beta= 
      0.13, SE = 0.04, p = 0.004), revealing an age-dependent association between ISD
      with NFTs. The ISD failed to show an acceptable level of diagnostic accuracy for
      MCI (AUC = 0.60). These findings suggest that increased cognitive dispersion is
      related to NFT pathology where age significantly affects this association.

PMID- 28453480
TI  - A Multifunctional Biocompatible Drug Candidate is Highly Effective in Delaying
      Pathological Signs of Alzheimer's Disease in 5XFAD Mice.
AB  - BACKGROUND: Metal-ion-chelation was suggested to prevent zinc and copper ions
      induced amyloid-beta (Abeta) aggregation and oxidative stress, both implicated in
      the pathophysiology of Alzheimer's disease (AD). In a quest for biocompatible
      metal-ion chelators potentially useful for AD therapy, we previously tested a
      series of nucleoside 5'-phosphorothioate derivatives as agents for decomposition
      of Cu(I)/Cu(II)/Zn(II)-Abeta-aggregates, and as inhibitors of OH radicals
      formation in Cu(I) or Fe(II) /H2O2 solution. Specifically, in our recent study we
      have identified 2-SMe-ADP(alpha-S), designated as SAS, as a most promising
      neuroprotectant. OBJECTIVE: To further explore SAS ability to protect the brain
      from Abeta toxicity both in vitro and in vivo. METHODS: We evaluated SAS ability
      to decompose or inhibit the formation of Abeta42-M(II) aggregates, and rescue
      primary neurons and astrocytes from Abeta42 toxicity. Furthermore, we aimed at
      exploring the therapeutic effect of SAS on behavioral and cognitive deficits in
      the 5XFAD mouse model of AD. RESULTS: We found that SAS can rescue primary
      culture of neurons and astrocytes from Abeta42 toxicity and to inhibit the
      formation and dissolve Abeta42-Zn(II)/Cu(II) aggregates. Furthermore, we show
      that SAS treatment can prevent behavioral disinhibition and ameliorate spatial
      working memory deficits in 5XFAD mice. Notably, the mice were treated at the age
      of 2 months, before the onset of AD symptoms, for a duration of 2 months, while
      the effect was demonstrated at the age of 6 months. CONCLUSION: Our results
      indicate that SAS has the potential to delay progression of core pathological
      characteristics of AD in the 5XFAD mouse model.

PMID- 28453481
TI  - The Association between Montreal Cognitive Assessment Memory Scores and
      Hippocampal Volume in a Neurodegenerative Disease Sample.
AB  - Despite widespread use, there have been few investigations into the
      neuroanatomical correlates of the Montreal Cognitive Assessment (MoCA). In a
      sample of 138 consecutive patients presenting with cognitive complaints, we
      report significant correlations between lower MoCA memory scores and smaller
      hippocampal volumes (r = 0.36-0.41, p < 0.001). We also report that the newly
      devised memory index score, designed to better capture encoding deficits than the
      standard delayed recall score, was not significantly better for predicting
      hippocampal volume. These initial results suggest that poor performance on the
      MoCA's memory section should prompt further evaluation for hippocampal atrophy.

PMID- 28453482
TI  - Higher Peripheral TREM2 mRNA Levels Relate to Cognitive Deficits and Hippocampal
      Atrophy in Alzheimer's Disease and Amnestic Mild Cognitive Impairment.
AB  - BACKGROUND: Variants in triggering receptor expressed on myeloid cells 2 (TREM2)
      are associated with increased Alzheimer's disease (AD) risk. Recent studies have
      reported inconsistent peripheral TREM2 mRNA expression levels and relationship
      with cognitive scores in AD and mild cognitive impairment (MCI). Additionally, no
      study has examined the association of peripheral TREM2 levels with neuroimaging
      measures in AD and MCI. OBJECTIVE: To determine peripheral TREM2 mRNA levels in
      AD, amnestic MCI (aMCI) and healthy controls, and the association with cognitive
      performance and brain structural changes. METHODS: We measured peripheral TREM2
      mRNA levels in 80 AD, 30 aMCI, and 86 healthy controls using real time polymerase
      chain reaction. TREM2 levels were correlated with various cognitive performance
      and brain volumes, correcting for APOE4 status. RESULTS: TREM2 mRNA levels were
      significantly higher in AD compared to controls and aMCI. Levels did not differ
      between aMCI and controls. Corrected for APOE4, higher TREM2 levels correlated
      with lower Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA)
      and episodic memory scores, and lower total grey matter and right hippocampal
      volumes. Whole-brain voxel-based morphometry analysis found negative association
      between TREM2 mRNA levels and grey matter volumes in temporal, parietal and
      frontal regions. AD subjects with MoCA scores <=20 had higher TREM2 levels
      correlating with smaller total grey matter, left hippocampal and right
      hippocampal volumes. CONCLUSION: Peripheral TREM2 mRNA levels are higher in AD
      and are associated with AD-related cognitive deficits and hippocampal atrophy.
      Our findings suggest that TREM2 may be a potential non-invasive peripheral
      biomarker for AD diagnosis.

PMID- 28453483
TI  - Remyelination: A Potential Therapeutic Strategy for Alzheimer's Disease?
AB  - Myelin is a lipid-rich multilamellar membrane that wraps around long segments of
      neuronal axons and it increases the conduction of action potentials, transports
      the necessary trophic support to the neuronal axons, and reduces the energy
      consumed by the neuronal axons. Together with axons, myelin is a prerequisite for
      the higher functions of the central nervous system and complex forms of network
      integration. Myelin impairments have been suggested to lead to neuronal
      dysfunction and cognitive decline. Accumulating evidence, including brain imaging
      and postmortem and genetic association studies, has implicated myelin impairments
      in Alzheimer's disease (AD). Increasing data link myelin impairments with amyloid
      beta (Abeta) plaques and tau hyperphosphorylation, which are both present in
      patients with AD. Moreover, aging and apolipoprotein E (ApoE) may be involved in
      the myelin impairments observed in patients with AD. Decreased neuronal activity,
      increased Abeta levels, and inflammation further damage myelin in patients with
      AD. Furthermore, treatments that promote myelination contribute to the recovery
      of neuronal function and improve cognition. Therefore, strategies targeting
      myelin impairment may provide therapeutic opportunities for patients with AD.

PMID- 28453484
TI  - Can Better Management of Periodontal Disease Delay the Onset and Progression of
      Alzheimer's Disease?
AB  - A risk factor relationship exists between periodontal disease and Alzheimer's
      disease (AD) via tooth loss, and improved memory following dental intervention.
      This links the microbial contribution from indigenous oral periodontal pathogens
      to the manifestation of chronic conditions, such as AD. Here, we use
      Porphyromonas gingivalis infection to illustrate its effect on mental health. P.
      gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial
      synergy and dysbiosis. Dysbiosis describes the residency of select commensals
      from the oral cavity following co-aggregation around the dominant keystone
      pathogen, such as P. gingivalis, to gain greater virulence. The initial process
      involves P. gingivalis disturbing neutrophil mediated innate immune responses in
      the healthy gingivae and then downregulating adaptive immune cell differentiation
      and development to invade, and subsequently, establish new dysbiotic bacterial
      communities. Immune responses affect the host in general and functionally via
      dietary adjustments caused by tooth loss. Studies from animals orally infected
      with P. gingivalis confirm this bacterium can transmigrate to distant organ sites
      (the brain) and contribute toward peripheral and intracerebral inflammation, and
      compromise vascular and microvascular integrity. In another study, P. gingivalis
      infection caused sleep pattern disturbances by altering glial cell light/dark
      molecular clock activity, and this, in turn, can affect the clearance of danger
      associated molecular patterns, such as amyloid-beta, via the glymphatic system.
      Since P. gingivalis can transmigrate to the brain and modulate organ-specific
      inflammatory innate and adaptive immune responses, this paper explores whether
      better management of indigenous periodontal bacteria could delay/prevent the
      onset and/or progression of dementia.

PMID- 28453485
TI  - Tau Oligomers in Sera of Patients with Alzheimer's Disease and Aged Controls.
AB  - Although tau protein was long regarded as an intracellular protein with several
      functions inside the cell, new evidence has shown tau secretion into the
      extracellular space. The active secretion of tau could be a physiological
      response of neurons to increased intracellular amounts of tau during the
      progression of tau pathology. We looked for potential differences in the serum
      levels of toxic tau oligomers in regards to cognitive impairment of subjects. We
      detected tau oligomers in the serum of Alzheimer's disease (AD) patients, but
      they were also present to some extent in the serum of healthy older subjects
      where the levels positively correlated with aging (Spearman r = 0.26, p = 0.016).
      On the contrary, we found lower levels of tau oligomers in the serum of mild
      cognitive impairment (MCI) (p = 0.033) and MCI-AD (p = 0.006) patients. These
      results could suggest that clearance of extracellular tau proteins takes place,
      in part, in the periphery. In the case of MCI patients, the lower levels of tau
      oligomers could be the result of impaired clearance of tau protein from
      interstitium to blood and consequent accumulation of tau aggregates in the brain.

PMID- 28453486
TI  - Cognitive Deficits after Cerebral Ischemia and Underlying Dysfunctional
      Plasticity: Potential Targets for Recovery of Cognition.
AB  - Cerebral ischemia affects millions of people worldwide and survivors suffer from
      long-term functional and cognitive deficits. While stroke and cardiac arrest are
      typically considered when discussing ischemic brain injuries, there is much
      evidence that smaller ischemic insults underlie neurodegenerative diseases,
      including Alzheimer's disease. The "regenerative" capacity of the brain relies on
      several aspects of plasticity that are crucial for normal functioning; less
      affected brain areas may take over function previously performed by irreversibly
      damaged tissue. To harness the endogenous plasticity mechanisms of the brain to
      provide recovery of cognitive function, we must first understand how these
      mechanisms are altered after damage, such as cerebral ischemia. In this review,
      we discuss the long-term cognitive changes that result after cerebral ischemia
      and how ischemia alters several plasticity processes. We conclude with a
      discussion of how current and prospective therapies may restore brain plasticity
      and allow for recovery of cognitive function, which may be applicable to several
      disorders that have a disruption of cognitive processing, including traumatic
      brain injury and Alzheimer's disease.

PMID- 28453487
TI  - Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers Predict Driving
      Decline: Brief Report.
AB  - We examined whether neuropsychiatric symptoms (NPS) interact with cerebrospinal
      fluid (CSF) biomarkers (amyloid-beta42 [Abeta42], tau, phosphorylated tau181
      [ptau181], tau/Abeta42, and ptau181/Abeta42) of Alzheimer's disease pathology to
      predict driving decline among cognitively-normal older adults (N = 116) aged
      >=65. Cox proportional hazards models examined time to receiving a rating of
      marginal or fail on the driving test. Age, education, and gender were adjusted in
      the models. Participants with more abnormal CSF (Abeta42, tau/Abeta42,
      ptau181/Abeta42) and NPS were faster to receive a marginal/fail on the road test
      compared to those without NPS. NPS interact with abnormal CSF biomarkers to
      impact driving performance among cognitively-normal older adults.

PMID- 28453488
TI  - Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and
      Amyloid-beta Aggregation in Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting
      the elderly population worldwide. Brain inflammation plays a key role in the
      progression of AD. Deposition of senile plaques in the brain stimulates an
      inflammatory response with the overexpression of pro-inflammatory mediators, such
      as the neuroinflammatory cytokine. interleukin-6. Curcumin has been revealed to
      be a potential agent for treating AD following different neuroprotective
      mechanisms, such as inhibition of aggregation and decrease in brain inflammation.
      We synthesized new curcumin derivatives with the aim of providing good anti
      aggregation capacity but also improved anti-inflammatory activity. Nine curcumin
      derivatives were synthesized by etherification and esterification of the aromatic
      region. From these derivatives, compound 8 exhibited an anti-inflammatory effect
      similar to curcumin, while compounds 3, 4, and 10 were more potent. Moreover,
      when the anti-aggregation activity is considered, compounds 3, 4, 5, 6, and 10
      showed biological activity in vitro. Compound 4 exhibited a strong anti
      aggregation effect higher than curcumin. Monofunctionalized curcumin derivatives
      showed better bioactivity than difunctionalized compounds. Moreover, the presence
      of bulky groups in the chemical structure of curcumin derivatives decreased
      bioactivity.

PMID- 28453489
TI  - Changes of Cerebrospinal Fluid Peptides due to Tauopathy.
AB  - Alzheimer's disease (AD) and progressive supranuclear palsy are two common
      neurodegenerative tauopathies, and the most common cause of progressive brain
      dementia in elderly affecting more than 35 million people. The tauopathies are
      characterized by abnormal deposition of microtubule associated protein tau into
      intracellular neurofibrillary tangles composed mainly of the hyperphosphorylated
      form of the protein. The diagnosis of tauopathies is based on the presence of
      clinical features and pathological changes. Over the last decade, there has been
      an intensive search for novel biochemical markers for clinical diagnosis of AD
      and other tauopathies. In the present study, we used transgenic rat model for
      tauopathy expressing human truncated tau protein (aa 151-391/4R) to analyze the
      cerebrospinal fluid (CSF) peptidome using liquid chromatography - matrix assisted
      laser desorption/ionization mass spectrometry (LC-MALDI TOF/TOF). From 345
      peptides, we identified a total of 175 proteins. Among them, 17 proteins were
      significantly altered in the CSF of transgenic rats. The following proteins were
      elevated in the CSF of transgenic rats when compared to the control animals:
      neurofilament light and medium chain, apolipoprotein E, gamma-synuclein,
      chromogranin A, reticulon-4, secretogranin-2, calsyntein-1 and -3, endothelin-3,
      neuroendocrine protein B72A, alpha-1-macroglobulin, and augurin. Interestingly
      most of the identified proteins were previously linked to AD and other
      tauopathies, indicating the significance of transgenic animals in biomarker
      validation.

PMID- 28453490
TI  - Plasma Amyloid-beta and Alzheimer's Disease-Related Changes in Late-Life
      Depression.
AB  - To elucidate an involvement of amyloid dysmetabolism in the pathophysiology of
      depression, we investigated associations of plasma amyloid-beta (Abeta) levels
      with Alzheimer's disease-related changes in neuroimaging and cognitive
      dysfunction in patients with late-life depression. Higher plasma Abeta40, but not
      Abeta42 nor Abeta40/Abeta42 ratio, was associated with higher degree of
      parahippocampal atrophy and lower verbal fluency performance. Indeed, high plasma
      Abeta40 predicted poor cognitive prognosis of depressed patients with mild
      cognitive impairment. As an anti-depressive treatment, electroconvulsive therapy
      (ECT) resulted in a marginally significant reduction of plasma Abeta40 compared
      to pharmacotherapy alone, suggesting protective effects of ECT against amyloid
      dysmetabolism.

PMID- 28453491
TI  - Neurofibrillary Tangles of Abetax-40 in Alzheimer's Disease Brains.
AB  - The two pathognomonic lesions in the brain of AD patients are senile plaques and
      intraneuronal neurofibrillary tangles (NFT). Previous studies have demonstrated
      that amyloid-beta (Abeta) is a component of both senile plaques and NFTs, and
      have showed that intracellular accumulation of Abeta is toxic for cells and
      precedes the appearance of extracellular amyloid deposits. Here we report that
      there are numerous intraneuronal NFT and extraneuronal NFT immunoreactive for
      Abetax-40 in which there is no co-localization with tau staining suggesting the
      existence of two different neurodegenerating populations associated with the
      intracellular accumulation of either tau protein or Abetax-40 in AD.

PMID- 28453494
TI  - Abstracts of the 25th European Workshop on Neonatology, Westerburg Castle,
      Germany, May 28th - 31st, 2017.

PMID- 28453493
TI  - S-Adenosylmethionine Attenuates Oxidative Stress and Neuroinflammation Induced by
      Amyloid-beta Through Modulation of Glutathione Metabolism.
AB  - Oxidative stress and neuroinflammation are mainly involved in the pathogenic
      mechanisms of Alzheimer's disease (AD). Amyloid-beta (Abeta), the main component
      of senile plaques, is a kind of strong inducer of oxidative stress. Glutathione
      is an endogenous antioxidant protecting cells from oxidative injury. S
      adenosylmethionine (SAM) produced in the methionine cycle is the primary methyl
      donor and the precursor of glutathione. In this study, the Abeta intrahippocampal
      injection rat model and cultured SH-SY5Y cells were used to explore the
      neuroprotective effect of SAM. We found that SAM could protect cells against
      Abeta-induced cellular injury by inhibition of oxidative stress and
      neuroinflammation. SAM administration could increase the endogenous antioxidant
      glutathione and potentiate the antioxidant enzymes activities. SAM might act as
      an antioxidant and be a potential candidate therapy for AD patients.

PMID- 28453492
TI  - Quantification of Butyrylcholinesterase Activity as a Sensitive and Specific
      Biomarker of Alzheimer's Disease.
AB  - Amyloid-beta (Abeta) plaques are a neuropathological hallmark of Alzheimer's
      disease (AD); however, a significant number of cognitively normal older adults
      can also have Abeta plaques. Thus, distinguishing AD from cognitively normal
      individuals with Abeta plaques (NwAbeta) based on Abeta plaque detection is
      challenging. It has been observed that butyrylcholinesterase (BChE) accumulates
      in plaques preferentially in AD. Thus, detecting BChE-associated plaques has the
      potential as an improved AD biomarker. We present Abeta, thioflavin-S, and BChE
      quantification of 26 postmortem brain tissues; AD (n = 8), NwAbeta (n = 6),
      cognitively normal without plaques (n = 8), and other common dementias including
      corticobasal degeneration, frontotemporal dementia with tau, dementia with Lewy
      bodies, and vascular dementia. Pathology burden in the orbitofrontal cortex,
      entorhinal cortex, amygdala, and hippocampal formation was determined and
      compared. The predictive value of Abeta and BChE quantification was determined,
      via receiver-operating characteristic plots, to evaluate their AD diagnostic
      performance using sensitivity, specificity, and area under curve (AUC) metrics.
      In general, Abeta and BChE-associated pathology were greater in AD, particularly
      in the orbitofrontal cortex. In this region, the largest increase (9.3-fold) was
      in BChE-associated pathology, observed between NwAbeta and AD, due to the virtual
      absence of BChE-associated plaques in NwAbeta brains. Furthermore, BChE did not
      associate with pathology of the other dementias. In this sample, BChE-associated
      pathology provided better diagnostic performance (AUC = 1.0,
      sensitivity/specificity = 100% /100%) when compared to Abeta (AUC = 0.98, 100%
      /85.7%). These findings highlight the predictive value of BChE as a biomarker for
      AD that could facilitate timely disease diagnosis and management.

PMID- 28453495
TI  - Constructing an Outcome Measure of Occupational Experience: An Application of
      Rasch Measurement Methods.
AB  - Rasch methods were used to evaluate and further develop the Daily Experiences of
      Pleasure, Productivity, and Restoration Profile (PPR Profile) into a health
      outcome measure of occupational experience. Analyses of 263 participant PPR
      Profiles focused on rating scale structure, dimensionality, and reliability. All
      rating scale categories increased with the intended meaning of the scales, but
      only 20 of the 21 category measures fit the Rasch rating scale model (RRSM).
      Several items also did not fit the RRSM and results of residual principal
      components analyses suggested possible second dimensions in each scale. More
      importantly, reliability coefficients were very low and participants could not be
      separated into more than one group as demonstrated by low person separation
      indices. The authors offer several recommendations for the next steps in the
      development of the PPR Profile as a health outcome measure of occupational
      experience.

PMID- 28453496
TI  - Comparing Imputation Methods for Trait Estimation Using the Rating Scale Model.
AB  - This study examined the performance of four methods of handling missing data for
      discrete response options on a questionnaire: (1) ignoring the missingness (using
      only the observed items to estimate trait levels); (2) nearest-neighbor hot deck
      imputation; (3) multiple hot deck imputation; and (4) semi-parametric multiple
      imputation. A simulation study examining three questionnaire lengths (41-, 20-,
      and 10-item) crossed with three levels of missingness (10, 25, and 40 percent)
      was conducted to see which methods best recovered trait estimates when data were
      missing completely at random and the polytomous items were scored with Andrich's
      (1978) rating scale model. The results showed that ignoring the missingness and
      semi-parametric imputation best recovered known trait levels across all
      conditions, with the semi-parametric technique providing the most precise trait
      estimates. This study demonstrates the power of specific objectivity in Rasch
      measurement, as ignoring the missingness leads to generally unbiased trait
      estimates.

PMID- 28453497
TI  - Rasch Analysis of a Behavioral Checklist for the Assessment of Pain in Critically
      Ill Adults.
AB  - Patients hospitalized in the intensive care unit (ICU) are often unable to report
      their pain, which is a problem since untreated pain is associated with negative
      health outcomes. The use of behavioral pain scales are recommended for the
      detection of the presence of pain in this vulnerable population. Previous
      validation studies have used classical techniques, and several psychometrics
      properties remain unknown. In this paper, data obtained from a behavioral
      checklist of dichotomized items was utilized to evaluate the instrument's
      dimensionality, its construct validity and its capacity to distinguish between
      levels of pain by using Rasch measurement. A sample of 239 ICU patients was used
      to collect the data. Results showed that, while unidimensionality was acceptable,
      concerns remained about the local independence and item fit indices. A third of
      the items showed misfit. Finally, while items had a great reliability (0.97),
      persons' measures had a rather low reliability (0.62) and only 1.28 strata of
      pain could be distinguished. The narrow range of pain levels in the sample could
      explain this poor performance and further study is needed, with a sample
      exhibiting a wider range of pain levels.

PMID- 28453498
TI  - Scale Anchoring with the Rasch Model.
AB  - Scale anchoring is a method to provide additional meaning to particular scores at
      different points along a score scale by identifying representative items
      associated with the particular scores. These items are then analyzed to write
      statements of what types of performance can be expected of a person with the
      particular scores to help test takers and other stakeholders better understand
      what it means to achieve the different scores. This article provides simple
      formulas that can be used to identify possible items to serve as scale anchors
      with the Rasch model. Specific attention is given to practical considerations and
      challenges that may be encountered when applying the formulas in different
      contexts. An illustrative example using data from a medical imaging certification
      program demonstrates how the formulas can be applied in practice.

PMID- 28453499
TI  - Evaluating Model-Data Fit by Comparing Parametric and Nonparametric Item Response
      Functions: Application of a Tukey-Hann Procedure.
AB  - This study describes an approach for examining model-data fit for the dichotomous
      Rasch model using Tukey-Hann item response functions (TH-IRFs). The procedure
      proposed in this paper is based on an iterative version of a smoothing technique
      proposed by Tukey (1977) for estimating nonparametric item response functions
      (IRFs). A root integrated squared error (RISE) statistic (Douglas and Cohen,
      2001) is used to compare the TH-IRFs to the Rasch IRFs. Data from undergraduate
      students at a large university are used to demonstrate this iterative smoothing
      technique. The RISE statistic is used for comparing the item response functions
      to assess model-data fit. A comparison between the residual based Infit and
      Outfit statistics and RISE statistics are also examined. The results suggest that
      the RISE statistic and TH-IRFs provide a useful analytical and graphical approach
      for evaluating item fit. Implications for research, theory and practice related
      to model-data fit are discussed.

PMID- 28453500
TI  - Rasch Derived Teachers' Emotions Questionnaire.
AB  - The purpose of this research was to estimate the reliability of the scores
      produced from and validity of the inferences drawn from the revised 90-item
      Teachers' Emotion Questionnaire consisting of three measures: frequency of
      emotional expressivity, self-efficacy for regulation of emotional expressivity
      when teaching, and self-efficacy for regulation of context-specific emotional
      expressivity. A void exists in an instrument assessing teachers' regulation and
      communication of their emotions. One-hundred seventeen practicing teachers
      participated in this study at Time 1 and 46 at Time 2. Rasch rating scale
      analyses indicated sufficient item and person separation and reliability and some
      support for the construct validity of the inferences drawn from the measures.
      Test re-test reliability for the person estimates was supported for all three
      measures over a four-week period: r=.592, p<.001, r=.473, p<.01, and r=.641,
      p<.001, respectively. Concurrent validity for the self-efficacy for regulation of
      emotional expressivity when teaching measure with the re-appraisal and
      suppression sub-scales on the Emotional Regulation Questionnaire (Gross and John,
      2003) was supported at Time 1. Modifications to rating scales and future
      directions for assessing teachers' emotions based on these results are discussed.

PMID- 28453501
TI  - Measuring Alcohol Marketing Engagement: The Development and Psychometric
      Properties of the Alcohol Marketing Engagement Scale.
AB  - Ample evidence exists in support of the influence of media, both traditional and
      electronic, on perceptions and engagement with alcohol marketing. We describe the
      development, calibration, and evidence for technical quality and utility for a
      new measure, the Alcohol Marketing Engagement Scale. Using two samples of college
      undergraduates (n1 = 199, n2 = 732), we collected field test responses to a total
      of 13 items. Initial support for scale validity is presented via correlations
      with attributes previously shown to be related to alcohol engagement. While the
      joint map of estimated scale locations of items and respondents indicates the
      need for further scale development, the results of the present analyses are
      promising. Implications for use in research are discussed.

PMID- 28453503
TI  - Preface.
AB  - Breast cancer (BC) is the most frequently diagnosed malignancy in young women and
      is the leading cause of cancer-related mortality in this age group. This issue
      represents a major public health problem in developing countries, where the
      incidence of BC is rapidly increasing and where young women represent a higher
      proportion of the total BC patient population compared to developed countries. In
      Latin America, BC among women aged 40 years or less accounts for up to 11% of new
      BC cases and 7% of all BC deaths. In Mexico, a very high proportion of the total
      number of BC patients are diagnosed in their early years, reaching up to 15% in
      some healthcare institutions.

PMID- 28453502
TI  - Identification of Key Genes Affecting Results of Hyperthermia in Osteosarcoma
      Based on Integrative ChIP-Seq/TargetScan Analysis.
AB  - BACKGROUND The purpose of this study was to research the effects of hyperthermia
      on osteosarcoma (OS) by integrating the Chromatin Immunoprecipitation with the
      generation sequencing (ChIP-Seq) and TargetScan analysis of heat shock
      transcription factor 1 (HSF1). MATERIAL AND METHODS The HSF1 ChIP-seq dataset of
      GSE60984 was downloaded from the Gene Expressed Omnibus (GEO) database. The HSF1
      binding sites were screened by MACS2 in OS cells after 10 and 20 min of
      hyperthermia, and they were annotated using the ChIPseeker package. The
      overlapped genes were selected out when HSF1-binding sites were located in the
      promoter region. The Database for Annotation, Visualization, and Integrated
      Discovery (DAVID) was used to perform Gene Ontology (GO) and Kyoto Encyclopedia
      of Genes and Genomes (KEGG) pathway enrichment analysis of the overlaps. The
      miRNA-gene pairs of the overlaps were screened out via TargetScan, and the miRNA
      gene-regulated network was constructed by Cytoscape software. RESULTS 1880 and
      1283 genes of promoter regions were obtained in the osteosarcoma cells after 10
      and 20 min of hyperthermia, respectively, and 889 of them were overlapped. The
      overlapped genes were enriched in 122 GO terms and 3 KEGG pathways. There were 13
      657 pairs involved in the miRNA-gene regulated network of the overlaps.
      CONCLUSIONS Some biomarkers were identified for OS treated with hyperthermia.
      Moreover, some GO terms (regulation of programmed cell death and regulation of
      cell death) and pathways (p53 signaling pathway, methane metabolism, and viral
      myocarditis) might be involved.

PMID- 28453504
TI  - The Epidemiological Challenges of Breast Cancer among Premenopausal Women in
      Limited Resource Settings.
AB  - Breast cancer is the most common malignant tumor among women of reproductive age
      and is also the most costly according to European reports. In this context, the
      aim of the present review is to identify factors that make breast cancer in
      premenopausal women an epidemiological challenge in developing countries.
      Epidemiological aspects of breast cancer, including risk factors, early detection
      methods, and treatment, are addressed. Breast cancer in premenopausal women
      should be included in the political and strategic agendas in developing countries
      to direct the necessary resources for prevention, detection, and control.

PMID- 28453505
TI  - Breast Cancer Intra-Tumor Heterogeneity: One Tumor, Different Entities.
AB  - In recent years, it has become evident that intra-tumor heterogeneity of breast
      cancer is a big challenge for the diagnosis, treatment, and clinical course of
      tumor-bearing patients. The advances in molecular biology and other technologies
      have led to the knowledge that a breast cancer tumor is comprised of multiple
      cellular entities. Here we review the two theories that have been described,
      trying to explain the origin of intra-tumor heterogeneity: clonal evolution and
      cancer stem cells. The first one considers that a single cell gives rise to many
      subpopulations through the accumulation of multiple aberrations, while the cancer
      stem cells theory foresees a hierarchical tumor evolution where only a few cells
      with self-renewal capacity give rise to different subpopulations. We also analyze
      the genetic, epigenetic, and microenvironment contributions to breast cancer
      intra-tumor heterogeneity. Finally, the clinical and therapeutic impact of intra
      tumor heterogeneity on the outcome of breast cancer patients is discussed.

PMID- 28453506
TI  - General Overview and Treatment Recommendations for Young Women with Breast
      Cancer.
AB  - Breast cancer in young women is a complex disease to manage due to its biological
      heterogeneity and special issues related to toxicity of different treatment
      strategies. Defining a cut-off for young age has been challenging since it is not
      clear whether the prognostic effect of age is continuously variable or whether
      there are certain thresholds at which the prognosis changes (e.g. those < 50
      years of age or <= 35 years of age). In this review article, we define young
      patients as those being premenopausal. In addition, we discuss the most recent
      data of the biological diversity of breast cancer arising in premenopausal
      patients and current treatment modalities in early and advanced settings.
      Survivorship, with special emphasis on the importance of early supportive care,
      is also discussed.

PMID- 28453508
TI  - Viable Options for Fertility Preservation in Breast Cancer Patients: A Focus on
      Latin America.
AB  - Thanks to the improved survival outcomes observed in recent years, a growing
      attention has been given to the quality of life issues faced by young women with
      breast cancer such as fertility preservation and concerns related to future
      pregnancies. However, several challenges remain for young women with breast
      cancer considering undergoing fertility preservation strategies. Further specific
      issues on this regard should be taken into account in Latin America, where
      patients and physicians face particular barriers that hinder the routine adoption
      of this practice. Hence, further efforts are needed to overcome these
      deficiencies and improve the correct referral of breast cancer patients to
      fertility preservation strategies. The aim of the present review is to focus on
      the risk of anticancer treatment-related premature ovarian failure and
      infertility in young breast cancer patients, to summarize the current knowledge
      on the available options for fertility preservation, and to discuss the safety
      issues of pregnancy in breast cancer survivors. Furthermore, this review aims to
      highlight the specific clinical challenges in this field encountered by
      healthcare providers and young breast cancer patients from Latin American
      countries.

PMID- 28453507
TI  - Genetic Cancer Risk Assessment for Breast Cancer in Latin America.
AB  - In Latin America, breast cancer is the most common malignancy in women, and
      limited available data suggest that up to 15% of all breast cancer cases in the
      region are hereditary. Genetic cancer risk assessment and counseling is a
      critical component of the appropriate clinical care of patients with hereditary
      breast cancer and their families. Unfortunately, genetic services are
      underdeveloped across Latin America, and access to genetic testing and counseling
      is very scarce in the region. Barriers contributing to the access to genetic care
      are high cost and lack of insurance coverage for genetic tests, insufficient
      oncogenetics training or expertise, nonexistence of genetic counseling as a
      clinical discipline, and lack of supportive healthcare policies. In this review,
      we highlight relevant initiatives undertaken in several Latin American countries
      aimed at creating genetic cancer risk assessment programs. Additionally, we
      present a review of the scientific literature on the current status of breast
      cancer genomics in Latin America, with specific emphasis on demographic
      indicators, access to cancer genetic care, training and strategies to improve
      outcomes, and international collaborations.

PMID- 28453509
TI  - Self-Image and Sexuality Issues among Young Women with Breast Cancer: Practical
      Recommendations.
AB  - BACKGROUND: Younger breast cancer survivors face a unique set of treatment
      related issues that have enormous impact on quality of life and psychological
      well-being. Although there is often a profound and distressing impact of
      treatment on self-image and sexual function, women rarely receive any attention
      for these issues. Unfortunately, most clinicians receive no training on how to
      inquire about these problems and most clinicians feel unprepared to discuss them.
      Often this silence is due to a lack of ready resources and uncertainty of
      appropriate strategies for rehabilitation. Cultural barriers may also contribute
      to lack of attention to these issues. OBJECTIVE: The aim of this paper is to not
      only elucidate common problems regarding self-image and sexual dysfunction, but
      to also offer concrete guidance about inquiry using a simple checklist approach
      as well as tips for resources and other evidence-based intervention strategies.
      Samples of a checklist and resource sheet for women written in Spanish are
      included, and cultural considerations within a Hispanic/Latina framework will be
      noted. As the great majority of young breast cancer patients are now becoming
      long-term survivors, it is essential for clinicians to learn how to address
      distressing treatment-related late effects including diminished self-image and
      sexual dysfunction.

PMID- 28453510
TI  - Is aspirin associated with diabetic retinopathy? The Singapore Epidemiology of
      Eye Disease (SEED) study.
AB  - BACKGROUND/AIMS: To determine the association between aspirin use and diabetic
      retinopathy (DR) among persons with diabetes, in a population-based, cross
      sectional study. METHODS: Subjects with diabetes aged >40 years from the
      Singapore Epidemiology of Eye Diseases Study were enrolled in this study. Retinal
      photographs were graded for DR according to the modified Airlie House
      classification system. Vision threatening diabetic retinopathy (VTDR) was defined
      as the presence of severe non-proliferative DR, or proliferative DR, or
      clinically significant macular oedema. The association between aspirin use and
      the presence of DR or VTDR was assessed using multivariable logistic regression
      models including age, gender, ethnicity, socioeconomic status, HbA1c, systolic
      blood pressure, anti-hypertension medicine, total cholesterol, anti-cholesterol
      medicine, BMI, current smoking status, diabetes duration, history of
      cardiovascular disease (CVD) and chronic kidney disease (CKD.). RESULTS: A total
      of 2,061 participants with diabetes and complete record of relevant systemic and
      DR data were included. Of these, 711 (34.5%) had any stage of DR, and among these
      177 (8.6%) had VTDR. After adjusting for co-variables listed, the association
      between aspirin use and VTDR was significant (OR = 1.69, P = 0.019), while the
      association between aspirin use and any DR was borderline (OR = 1.31, P = 0.063).
      Aspirin use was not associated with either DR or VTDR after additional adjustment
      of CVD and CKD. Further stratification by history of CVD or CKD showed no
      association between aspirin use and DR/VTDR in either subgroup. CONCLUSION:
      Aspirin use was not significantly associated with DR but might be an indicator of
      diabetic complications (CVD, CKD) that were co-present with more severe DR type.
      Future longitudinal studies are warranted to confirm our findings.

PMID- 28453511
TI  - No contribution of lifestyle and environmental exposures to gender discrepancy of
      liver disease severity in chronic hepatitis b infection: Observations from the
      Haimen City cohort.
AB  - BACKGROUND: Previous studies have noted significant gender difference in the risk
      of liver cancer among hepatitis B chronic infection patients. Some indicated that
      it might be due to lifestyle-related differences. This paper tests whether or not
      such a gender discrepancy among the chronic hepatitis B population is confounded
      by lifestyle and environment related exposures. METHODS: We retrieved a sample of
      1863 participants from a prospective cohort in Haimen City, China in 2003. Liver
      disease severity was categorized as "normal", "mild", "moderate", and "severe"
      based on a clinical diagnosis. Lifestyle and environmental exposures were
      measured by questionnaires. We used factor analysis and individual variables to
      represent lifestyle and environmental exposures. We applied the cumulative logit
      models to estimate the effect of gender on liver disease severity and how it was
      impacted by lifestyle and environmental exposures. RESULTS: Gender and HBeAg
      positivity were independent risk factors for more severe liver disease. Compared
      to females, males were 2.08 times as likely to develop more severe liver disease
      (95% CI: 1.66-2.61). Participants who were HBeAg positivite were 2.19 times (95%
      CI: 1.61-2.96) as likely to develop more severe liver disease compared to those
      who were negative. Controlling for lifestyle and environmental exposures did not
      change these estimations. CONCLUSIONS: Males in the HBV infected population have
      an increased risk of severe liver disease. This gender effect is independent of
      the lifestyle and environmental exposures addressed in this study. Our findings
      support the hypothesis that gender discrepancies in HCC risk are attributable to
      intrinsic differences between males and females.

PMID- 28453512
TI  - A reproducible semi-automatic method to quantify the muscle-lipid distribution in
      clinical 3D CT images of the thigh.
AB  - Many studies use threshold-based techniques to assess in vivo the muscle, bone
      and adipose tissue distribution of the legs using computed tomography (CT)
      imaging. More advanced techniques divide the legs into subcutaneous adipose
      tissue (SAT), anatomical muscle (muscle tissue and adipocytes within the muscle
      border) and intra- and perimuscular adipose tissue. In addition, a so-called
      muscle density directly derived from the CT-values is often measured. We
      introduce a new integrated approach to quantify the muscle-lipid system (MLS)
      using quantitative CT in patients with sarcopenia or osteoporosis. The analysis
      targets the thigh as many CT studies of the hip do not include entire legs The
      framework consists of an anatomic coordinate system, allowing delineation of
      reproducible volumes of interest, a robust semi-automatic 3D segmentation of the
      fascia and a comprehensive method to quantify of the muscle and lipid
      distribution within the fascia. CT density-dependent features are calibrated
      using subject-specific internal CT values of the SAT and external CT values of an
      in scan calibration phantom. Robustness of the framework with respect to operator
      interaction, image noise and calibration was evaluated. Specifically, the impact
      of inter- and intra-operator reanalysis precision and addition of Gaussian noise
      to simulate lower radiation exposure on muscle and AT volumes, muscle density and
      3D texture features quantifying MLS within the fascia, were analyzed. Existing
      data of 25 subjects (age: 75.6 +/- 8.7) with porous and low-contrast muscle
      structures were included in the analysis. Intra- and inter-operator reanalysis
      precision errors were below 1% and mostly comparable to 1% of cohort variation of
      the corresponding features. Doubling the noise changed most 3D texture features
      by up to 15% of the cohort variation but did not affect density and volume
      measurements. The application of the novel technique is easy with acceptable
      processing time. It can thus be employed for a comprehensive quantification of
      the muscle-lipid system enabling radiomics approaches to musculoskeletal
      disorders.

PMID- 28453514
TI  - Gut Check: The evolution of an educational board game.
AB  - The "gamification" of science has gained a lot of traction in recent years, and
      games that convey scientific concepts or themes are increasingly popular. While a
      number of existing games touch on microbiology, very few consider the beneficial
      (as opposed to the detrimental) aspects of microbes. We designed a board game
      called "Gut Check: The Microbiome Game" to fill this gap. The game is meant to be
      both educational as well as challenging and fun. Here we discuss the development
      of the game, some of the logistics of game development in this context, and offer
      suggestions for others thinking of similar projects.

PMID- 28453513
TI  - Genetic diversity and population structure of the tsetse fly Glossina fuscipes
      fuscipes (Diptera: Glossinidae) in Northern Uganda: Implications for vector
      control.
AB  - Uganda is the only country where the chronic and acute forms of human African
      Trypanosomiasis (HAT) or sleeping sickness both occur and are separated by < 100
      km in areas north of Lake Kyoga. In Uganda, Glossina fuscipes fuscipes is the
      main vector of the Trypanosoma parasites responsible for these diseases as well
      for the animal African Trypanosomiasis (AAT), or Nagana. We used highly
      polymorphic microsatellite loci and a mitochondrial DNA (mtDNA) marker to provide
      fine scale spatial resolution of genetic structure of G. f. fuscipes from 42
      sampling sites from the northern region of Uganda where a merger of the two
      disease belts is feared. Based on microsatellite analyses, we found that G. f.
      fuscipes in northern Uganda are structured into three distinct genetic clusters
      with varying degrees of interconnectivity among them. Based on genetic assignment
      and spatial location, we grouped the sampling sites into four genetic units
      corresponding to northwestern Uganda in the Albert Nile drainage, northeastern
      Uganda in the Lake Kyoga drainage, western Uganda in the Victoria Nile drainage,
      and a transition zone between the two northern genetic clusters characterized by
      high level of genetic admixture. An analysis using HYBRIDLAB supported a hybrid
      swarm model as most consistent with tsetse genotypes in these admixed samples.
      Results of mtDNA analyses revealed the presence of 30 haplotypes representing
      three main haplogroups, whose location broadly overlaps with the microsatellite
      defined clusters. Migration analyses based on microsatellites point to moderate
      migration among the northern units located in the Albert Nile, Achwa River, Okole
      River, and Lake Kyoga drainages, but not between the northern units and the
      Victoria Nile drainage in the west. Effective population size estimates were
      variable with low to moderate sizes in most populations and with evidence of
      recent population bottlenecks, especially in the northeast unit of the Lake Kyoga
      drainage. Our microsatellite and mtDNA based analyses indicate that G. f.
      fuscipes movement along the Achwa and Okole rivers may facilitate northwest
      expansion of the Rhodesiense disease belt in Uganda. We identified tsetse
      migration corridors and recommend a rolling carpet approach from south of Lake
      Kyoga northward to minimize disease dispersal and prevent vector re-colonization.
      Additionally, our findings highlight the need for continuing tsetse monitoring
      efforts during and after control.

PMID- 28453515
TI  - Reliable reference genes for normalization of gene expression data in tea plants
      (Camellia sinensis) exposed to metal stresses.
AB  - Tea plants [Camellia sinensis (L.) O. Kuntze] are an important leaf-type crop
      that are widely used for the production of non-alcoholic beverages in the world.
      Exposure to excessive amounts of heavy metals adversely affects the quality and
      yield of tea leaves. To analyze the molecular responses of tea plants to heavy
      metals, a reliable quantification of gene expression is important and of major
      importance herein is the normalization of the measured expression levels for the
      target genes. Ideally, stably expressed reference genes should be evaluated in
      all experimental systems. In this study, 12 candidate reference genes (i.e., 18S
      rRNA, Actin, CYP, EF-1alpha, eIF-4alpha, GAPDH, MON1, PP2AA3, TBP, TIP41, TUA,
      and UBC) were cloned from tea plants, and the stability of their expression was
      examined systematically in 60 samples exposed to diverse heavy metals (i.e.,
      manganese, aluminum, copper, iron, and zinc). Three Excel-based algorithms
      (geNorm, NormFinder, and BestKeeper) were used to evaluate the expression
      stability of these genes. PP2AA3 and 18S rRNA were the most stably expressed
      genes, even though their expression profiles exhibited some variability.
      Moreover, commonly used reference genes (i.e., GAPDH and TBP) were the least
      appropriate reference genes for most samples. To further validate the suitability
      of the analyzed reference genes, the expression level of a phytochelatin synthase
      gene (i.e., CsPCS1) was determined using the putative reference genes for data
      normalizations. Our results may be beneficial for future studies involving the
      quantification of relative gene expression levels in tea plants.

PMID- 28453517
TI  - A comparison of multiple testing adjustment methods with block-correlation
      positively-dependent tests.
AB  - In high dimensional data analysis (such as gene expression, spatial epidemiology,
      or brain imaging studies), we often test thousands or more hypotheses
      simultaneously. As the number of tests increases, the chance of observing some
      statistically significant tests is very high even when all null hypotheses are
      true. Consequently, we could reach incorrect conclusions regarding the
      hypotheses. Researchers frequently use multiplicity adjustment methods to control
      type I error rates-primarily the family-wise error rate (FWER) or the false
      discovery rate (FDR)-while still desiring high statistical power. In practice,
      such studies may have dependent test statistics (or p-values) as tests can be
      dependent on each other. However, some commonly-used multiplicity adjustment
      methods assume independent tests. We perform a simulation study comparing several
      of the most common adjustment methods involved in multiple hypothesis testing,
      under varying degrees of block-correlation positive dependence among tests.

PMID- 28453516
TI  - On a fractional order calculus model in diffusion weighted breast imaging to
      differentiate between malignant and benign breast lesions detected on X-ray
      screening mammography.
AB  - OBJECTIVE: To evaluate a fractional order calculus (FROC) model in diffusion
      weighted imaging to differentiate between malignant and benign breast lesions in
      breast cancer screening work-up using recently introduced parameters (betaFROC,
      DFROC and MUFROC). MATERIALS AND METHODS: This retrospective analysis within a
      prospective IRB-approved study included 51 participants (mean 58.4 years) after
      written informed consent. All patients had suspicious screening mammograms and
      indication for biopsy. Prior to biopsy, full diagnostic contrast-enhanced MRI
      examination was acquired including diffusion-weighted-imaging (DWI, b =
      0,100,750,1500 s/mm2). Conventional apparent diffusion coefficient Dapp and FROC
      parameters (betaFROC, DFROC and MUFROC) as suggested further indicators of
      diffusivity components were measured in benign and malignant lesions. Receiver
      operating characteristics (ROC) were calculated to evaluate the diagnostic
      performance of the parameters. RESULTS: 29/51 patients histopathologically
      revealed malignant lesions. The analysis revealed an AUC for Dapp of 0.89 (95% CI
      0.80-0.98). For FROC derived parameters, AUC was 0.75 (0.60-0.89) for DFROC, 0.59
      (0.43-0.75) for betaFROC and 0.59 (0.42-0.77) for MUFROC. Comparison of the AUC
      curves revealed a significantly higher AUC of Dapp compared to the FROC
      parameters DFROC (p = 0.009), betaFROC (p = 0.003) and MUFROC (p = 0.001).
      CONCLUSION: In contrast to recent description in brain tumors, the apparent
      diffusion coefficient Dapp showed a significantly higher AUC than the recently
      proposed FROC parameters betaFROC, DFROC and MUFROC for differentiating between
      malignant and benign breast lesions. This might be related to the intrinsic high
      heterogeneity within breast tissue or to the lower maximal b-value used in our
      study.

PMID- 28453518
TI  - LC-MS-MS quantitative analysis reveals the association between FTO and DNA
      methylation.
AB  - Fat mass and obesity-associated protein (FTO) is alpha-ketoglutarate-dependent
      dioxygenase and responsible for demethylating N6-methyladenosine (m6A) in mRNA, 3
      methylthymine (m3T) in single-stranded DNA (ssDNA) and 3-methyluracil (m3U) in
      single-stranded RNA (ssRNA). Its other function remains unknown but thousands of
      mammalian DNA show 5-methyl-2'-deoxycytidine (5mdC) modification and 5mdC
      demethylases are required for mammalian energy homeostasis and fertility. Here,
      we aimed to confirm whether FTO proteins can demethylate 5mdC in DNA. However, we
      found that FTO exhibits no potent demethylation activity against 5mdC in vitro
      and in vivo by using liquid chromatography-tandem mass spectrometry (LC-MS-MS).
      The result showed FTO demethylase has the characteristics of high substrates
      specificity and selectivity. In addition, we also used immunofluorescence
      technique to demonstrate overexpression of wild type TET2, but not FTO and mutant
      TET2 in Hela cells results in higher levels of 5-hydroxymethyl-2'-deoxycytidine
      (5hmdC) generated from 5mdC. In conclusion, our results not only reveal the
      enzymatic activity of FTO, but also may facilitate the future discovery of
      proteins involved in epigenetic modification function.

PMID- 28453519
TI  - Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain
      malformation.
AB  - Mid-hindbrain malformations can occur during embryogenesis through a disturbance
      of transient and localized gene expression patterns within these distinct brain
      structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are
      key for controlling the spatiotemporal activation of Rho GTPase, to modulate
      cytoskeleton dynamics, cell division, and cell migration. We identified, by means
      of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a
      cause of intellectual disability, a midbrain-hindbrain malformation, and mild
      microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show
      that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is
      associated with a shift of mitotic spindle plane orientation, putatively favoring
      more symmetric divisions. The ARHGEF2 mutation leads to reduction in the
      activation of the RhoA/ROCK/MLC pathway crucial for cell migration. We
      demonstrate that the human brain malformation is recapitulated in Arhgef2 mutant
      mice and identify an aberrant migration of distinct components of the
      precerebellar system as a pathomechanism underlying the midbrain-hindbrain
      phenotype. Our results highlight the crucial function of ARHGEF2 in human brain
      development and identify a mutation in ARHGEF2 as novel cause of a
      neurodevelopmental disorder.

PMID- 28453520
TI  - WDR23 regulates NRF2 independently of KEAP1.
AB  - Cellular adaptation to stress is essential to ensure organismal survival.
      NRF2/NFE2L2 is a key determinant of xenobiotic stress responses, and loss of
      negative regulation by the KEAP1-CUL3 proteasome system is implicated in several
      chemo- and radiation-resistant cancers. Advantageously using C. elegans alongside
      human cell culture models, we establish a new WDR23-DDB1-CUL4 regulatory axis for
      NRF2 activity that operates independently of the canonical KEAP1-CUL3 system.
      WDR23 binds the DIDLID sequence within the Neh2 domain of NRF2 to regulate its
      stability; this regulation is not dependent on the KEAP1-binding DLG or ETGE
      motifs. The C-terminal domain of WDR23 is highly conserved and involved in
      regulation of NRF2 by the DDB1-CUL4 complex. The addition of WDR23 increases
      cellular sensitivity to cytotoxic chemotherapeutic drugs and suppresses NRF2 in
      KEAP1-negative cancer cell lines. Together, our results identify WDR23 as an
      alternative regulator of NRF2 proteostasis and uncover a cellular pathway that
      regulates NRF2 activity and capacity for cytoprotection independently of KEAP1.

PMID- 28453521
TI  - Soy moratorium impacts on soybean and deforestation dynamics in Mato Grosso,
      Brazil.
AB  - Previous research has established the usefulness of remotely sensed vegetation
      index (VI) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) to
      characterize the spatial dynamics of agriculture in the state of Mato Grosso
      (MT), Brazil. With these data it has become possible to track MT agriculture,
      which accounts for ~85% of Brazilian Amazon soy production, across periods of
      several years. Annual land cover (LC) maps support investigation of the
      spatiotemporal dynamics of agriculture as they relate to forest cover and
      governance and policy efforts to lower deforestation rates. We use a unique,
      spatially extensive 9-year (2005-2013) ground reference dataset to classify, with
      approximately 80% accuracy, MODIS VI data, merging the results with carefully
      processed annual forest and sugarcane coverages developed by Brazil's National
      Institute for Space Research to produce LC maps for MT for the 2001-2014 crop
      years. We apply the maps to an evaluation of forest and agricultural
      intensification dynamics before and after the Soy Moratorium (SoyM), a governance
      effort enacted in July 2006 to halt deforestation for the purpose of soy
      production in the Brazilian Amazon. We find the pre-SoyM deforestation rate to be
      more than five times the post-SoyM rate, while simultaneously observing the pre
      SoyM forest-to-soy conversion rate to be more than twice the post-SoyM rate.
      These observations support the hypothesis that SoyM has played a role in reducing
      both deforestation and subsequent use for soy production. Additional analyses
      explore the land use tendencies of deforested areas and the conceptual framework
      of horizontal and vertical agricultural intensification, which distinguishes
      production increases attributable to cropland expansion into newly deforested
      areas as opposed to implementation of multi-cropping systems on existing
      cropland. During the 14-year study period, soy production was found to shift from
      predominantly single-crop systems to majority double-crop systems.

PMID- 28453522
TI  - Potential biological pathways linking Type-D personality and poor health: A cross
      sectional investigation.
AB  - BACKGROUND: Type-D personality, defined as a combination of high negative affect
      and high social isolation, has been associated with poor health outcomes.
      However, pathways underlying this association are largely unknown. We
      investigated the relationship between Type-D personality and several biological
      and behavioral pathways including the autonomic nervous system, the immune
      system, glucose regulation and sleep in a large, apparently healthy sample.
      METHODS: Data from a total of 646 respondents (age 41.6+/-11.5, 12,2% women) were
      available for analysis. Persons with Type-D (negative affect and social isolation
      score >=10) were contrasted with those without Type-D. Measures of plasma
      fibrinogen levels, white blood cell count, high sensitivity C-reactive protein,
      fasting plasma glucose (FPG), cholesterol, high-density and low-density
      lipoprotein, glycated hemoglobin (HbA1c), creatinine, triglycerides, and albumin
      were derived from fasting blood samples. Urine norepinephrine and free cortisol
      were determined by high-performance liquid chromatography. Time-domain heart rate
      variability (HRV) measures were calculated for the 24hr recording period and for
      nighttime separately. RESULTS: Persons with Type-D had higher HbA1c, FPG, and
      fibrinogen, and lower nighttime HRV than those without Type-D, suggesting worse
      glycemic control, systemic inflammation and poorer autonomic nervous system
      modulation in Type-D persons. In addition, those with Type-D reported less social
      support and greater sleep difficulties while no group differences were observed
      for alcohol and cigarette consumption, physical activity and body mass index.
      CONCLUSIONS: Findings provide some of the first evidence for multiple possible
      biological and behavioral pathways between Type-D personality and increased
      morbidity and mortality.

PMID- 28453523
TI  - The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated
      by polymer formation and can cleave DNA substrates in trans.
AB  - Crossing over between homologs is initiated in meiotic prophase by the formation
      of DNA double-strand breaks that occur throughout the genome. In the major
      interference-responsive crossover pathway in baker's yeast, these breaks are
      resected to form 3' single-strand tails that participate in a homology search,
      ultimately forming double Holliday junctions (dHJs) that primarily include both
      homologs. These dHJs are resolved by endonuclease activity to form exclusively
      crossovers, which are critical for proper homolog segregation in Meiosis I.
      Recent genetic, biochemical, and molecular studies in yeast are consistent with
      the hypothesis of Mlh1-Mlh3 DNA mismatch repair complex acting as the major
      endonuclease activity that resolves dHJs into crossovers. However, the mechanism
      by which the Mlh1-Mlh3 endonuclease is activated is unknown. Here, we provide
      evidence that Mlh1-Mlh3 does not behave like a structure-specific endonuclease
      but forms polymers required to generate nicks in DNA. This conclusion is
      supported by DNA binding studies performed with different-sized substrates that
      contain or lack polymerization barriers and endonuclease assays performed with
      varying ratios of endonuclease-deficient and endonuclease-proficient Mlh1-Mlh3.
      In addition, Mlh1-Mlh3 can generate religatable double-strand breaks and form an
      active nucleoprotein complex that can nick DNA substrates in trans. Together
      these observations argue that Mlh1-Mlh3 may not act like a canonical, RuvC-like
      Holliday junction resolvase and support a novel model in which Mlh1-Mlh3 is
      loaded onto DNA to form an activated polymer that cleaves DNA.

PMID- 28453524
TI  - Peripheral huntingtin silencing does not ameliorate central signs of disease in
      the B6.HttQ111/+ mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
      whose predominant neuropathological signature is the selective loss of medium
      spiny neurons in the striatum. Despite this selective neuropathology, the mutant
      protein (huntingtin) is found in virtually every cell so far studied, and,
      consequently, phenotypes are observed in a wide range of organ systems both
      inside and outside the central nervous system. We, and others, have suggested
      that peripheral dysfunction could contribute to the rate of progression of
      striatal phenotypes of HD. To test this hypothesis, we lowered levels of
      huntingtin by treating mice with antisense oligonucleotides (ASOs) targeting the
      murine Huntingtin gene. To study the relationship between peripheral huntingtin
      levels and striatal HD phenotypes, we utilized a knock-in model of the human HD
      mutation (the B6.HttQ111/+ mouse). We treated mice with ASOs from 2-10 months of
      age, a time period over which significant HD-relevant signs progressively develop
      in the brains of HttQ111/+ mice. Peripheral treatment with ASOs led to persistent
      reduction of huntingtin protein in peripheral organs, including liver (64%
      knockdown), brown adipose (66% knockdown), and white adipose tissues (71%
      knockdown). This reduction was not associated with alterations in the severity of
      HD-relevant signs in the striatum of HttQ111/+ mice at the end of the study,
      including transcriptional dysregulation, the accumulation of neuronal
      intranuclear inclusions, and behavioral changes such as subtle hypoactivity and
      reduced exploratory drive. These results suggest that the amount of peripheral
      reduction achieved in the current study does not significantly impact the
      progression of HD-relevant signs in the central nervous system.

PMID- 28453526
TI  - With whom do you feel most intimate?: Exploring the quality of Facebook
      friendships in relation to similarities and interaction behaviors.
AB  - It is widely accepted that people tend to associate more and feel closer to those
      who share similar attributes with themselves. Most of the research on the
      phenomenon has been carried out in face-to-face contexts. However, it is
      necessary to study the phenomenon in computer-mediated contexts as well.
      Exploring Facebook is important in that friendships within the network indicate a
      broader spectrum of friends, ranging from complete strangers to confiding
      relations. Also, since diverse communication methods are available on Facebook,
      which method a user adopts to interact with a "friend" could influence the
      quality of the relationship, i.e. intimacy. Thus, current research aims to test
      whether people in computer-mediated contexts do perceive more intimacy toward
      friends who share similar traits, and further, aims to examine which interaction
      methods influence the closeness of relationship by collecting activity data of
      users on Facebook. Results from current study show traits related to intimacy in
      the online context of Facebook. Moreover, in addition to the interaction type
      itself, direction of the interaction influenced how intimate users feel towards
      their friends. Overall findings suggest that further investigation on the
      dynamics of online communication methods used in developing and maintaining
      relationships is necessary.

PMID- 28453525
TI  - High mortality among male HIV-infected patients after prison release: ART is not
      enough after incarceration with HIV.
AB  - CONTEXT: French Guiana is a South American French territory, where HIV prevalence
      consistently exceeds 1% in the adult population. In the only correctional
      facility, HIV prevalence fluctuates at around 4%. AIMS: After describing the
      population of HIV-positive inmates, we aimed to evaluate mortality after release
      from the correctional facility, and to identify its predictive factors.
      RATIONALE: Outside North American settings, data on treatment outcome and vital
      status of HIV-positive former inmates are scarce. There were no data in French
      Guiana. Filling this gap represents a basis for potential improvements. METHODS:
      All HIV-infected adults released from an incarceration of 30 days or more,
      between 2007 and 2013, were enrolled in a retrospective cohort study. Mortality
      was described over time, one to seven years following release, using Kaplan-Meier
      estimates. Factors associated with mortality were identified through a non
      parametric survival regression model. RESULTS: 147 former inmates were included.
      The male to female ratio was 4.4. The median age was 37.3 years. The majority
      were migrants, 25.8% were homeless, 70.1% suffered from substance abuse, with
      34.0% of crack-cocaine users. On admission, 78.1% had an early HIV-stage
      infection (CDC-stage A), with a median CD4 count of 397.5/mm3, 34.0% had one
      comorbidity, mainly hypertension. Upon release, 50.3% were on ART. Reasons for
      not being treated were not fulfilling the criteria for 74.6%, and refusing for
      15.1%. Before release, 84.5% of the patients on ART had a viral load<=200cp/ml.
      After release, 8.2% of the cohort had died, with a crude incidence of 33.8/1000
      person-years. All recorded deaths were males, with an incidence of 42.2/1000
      person-years. Comparing with the age-specific mortality rates for males in French
      Guiana, the standardized mortality ratio was 14.8. In multivariate analysis,
      factors associated with death were age and CD4 count before release. CONCLUSION:
      Despite access to ART while incarcerated, with good virological outcome, the post
      release mortality was very high for males, almost 15 times what is observed in
      the general male population living in French Guiana, after age standardization.
      Access to ART in correctional facilities may be a necessary, but not sufficient
      condition to protect male inmates from death after release.

PMID- 28453527
TI  - Altered nucleocytoplasmic proteome and transcriptome distributions in an in vitro
      model of amyotrophic lateral sclerosis.
AB  - Aberrant nucleocytoplasmic localization of proteins has been implicated in many
      neurodegenerative diseases. Evidence suggests that cytoplasmic mislocalization of
      nuclear proteins such as transactive response DNA-binding protein 43 (TDP-43) and
      fused in sarcoma (FUS) may be associated with neurotoxicity in amyotrophic
      lateral sclerosis (ALS) and frontotemporal lobar degeneration. This study
      investigated the changes in nucleocytoplasmic distributions of the proteome and
      transcriptome in an in vitro model of ALS. After subcellular fractionation of
      motor neuron-like cell lines expressing wild-type or G93A mutant hSOD1,
      quantitative mass spectrometry and next-generation RNA sequencing (RNA-seq) were
      performed for the nuclear and cytoplasmic compartments. A subset of the results
      was validated via immunoblotting. A total of 1,925 proteins were identified in
      either the nuclear or cytoplasmic fractions, and 32% of these proteins were
      quantified in both fractions. The nucleocytoplasmic distribution of 37 proteins
      was significantly changed in mutant cells with nuclear and cytoplasmic shifts in
      13 and 24 proteins, respectively (p<0.05). The proteins shifted towards the
      nucleus were enriched regarding pathways of RNA transport and processing (Dhx9,
      Fmr1, Srsf3, Srsf6, Tra2b), whereas protein folding (Cct5, Cct7, Cct8), aminoacyl
      tRNA biosynthesis (Farsb, Nars, Txnrd1), synaptic vesicle cycle (Cltc, Nsf), Wnt
      signalling (Cltc, Plcb3, Plec, Psmd3, Ruvbl1) and Hippo signalling (Camk2d,
      Plcb3, Ruvbl1) pathways were over-represented in the proteins shifted to the
      cytoplasm. A weak correlation between the changes in protein and mRNA levels was
      found only in the nucleus, where mRNA was relatively abundant in mutant cells.
      This study provides a comprehensive dataset of the nucleocytoplasmic distribution
      of the proteome and transcriptome in an in vitro model of ALS. An integrated
      analysis of the nucleocytoplasmic distribution of the proteome and transcriptome
      demonstrated multiple candidate pathways including RNA processing/transport and
      protein synthesis and folding that may be relevant to the pathomechanism of ALS.

PMID- 28453528
TI  - Guidance in author instructions of hematology and oncology journals: A cross
      sectional and longitudinal study.
AB  - BACKGROUND: The debate about the value of biomedical publications led to
      recommendations for improving reporting quality. It is unclear to what extent
      these recommendations have been endorsed by journals. We analyzed whether
      specific recommendations were included in author instructions, which journal
      characteristics were associated with their endorsement, how endorsement of the
      domains changed and whether endorsement was associated with change of impact
      factor between 2010 and 2015. METHODS: We considered two study samples consisting
      of "Hematology" and "Oncology" journals of the Journal Citation Report 2008 and
      2014, respectively. We extracted information regarding endorsement of the (1)
      recommendations of the International Committee of Medical Journal Editors, of (2)
      reporting guidelines, (3) requirement for trial registration and (4) disclosure
      of conflicts of interest. Data extraction was done by reading the author
      instructions before conducting a text search with keywords. We calculated a
      global generalized linear mixed effects model for endorsement of each of the four
      domains followed by separate multivariable logistic regression models and a
      longitudinal analysis. We defined endorsement as the author instructions saying
      that they approve the use of the recommendations. RESULTS: In 2015, the ICMJE
      recommendations were mentioned in author instructions of 156 journals (67.5%).
      CONSORT was referred to by 77 journals (33.3%); MOOSE, PRISMA, STARD and STROBE
      were referred to by less than 15% of journals. There were 99 journals (42.9%)
      that recommended or required trial registration, 211 (91.3%) required authors to
      disclose conflicts of interest. Journal impact factor, journal start year and
      geographical region were positively associated with endorsement of any of the
      four domains. The overall endorsement of all domains increased between 2010 and
      2015. The endorsement of any domain in 2010 seemed to be associated with an
      increased impact factor in 2014. CONCLUSION: Hematology and oncology journals
      endorse major recommendations to various degrees. Endorsement is increasing
      slowly over time and might be positively associated with the journals' impact
      factor.

PMID- 28453529
TI  - Effect of mild hypothermia preconditioning against low temperature (4 degrees C)
      induced rat liver cell injury in vitro.
AB  - Bioartificial liver holds special position in the field of regenerative medicine,
      and cold environment at 4C is widely used for the short storage of both organ and
      liver cell for later application. However, the disadvantages of such cold storage
      could influence cell viability and lead to cell apoptosis in different degrees.
      In this study, we mainly explore the pre-protective effect of mild hypothermia
      against low temperature (4C)-induced rat liver cell injury in vitro. Our results
      indicated that the precondition with mild hypothermia could increase cell
      viability, such as cell proliferation, LDH regulation and glycogen synthesis
      ability of liver cell. The precondition also decreased the ROS production and
      relieved cell apoptosis in liver cells. Compared with the model group, the
      mitochondrial membrane potential was restored in the mild hypothermia group, as
      well as the mitochondrial membrane permeability transition pore opening,
      indicating that the therapeutic mechanism was related to mitochondrial
      protection. Further analysis showed that PI3K-Akt-GSK3beta signal pathway might
      be associated with the pre-protective effect of mild hypothermia. Thus, our study
      suggested that the precondition with mild hypothermia hold the protective effect
      for liver cell in cold environment, and further developed a novel strategy for
      the storage of liver seed cells, even bioartificial liver.

PMID- 28453530
TI  - Intracellular signaling entropy can be a biomarker for predicting the development
      of cervical intraepithelial neoplasia.
AB  - While the mortality rates for cervical cancer have been drastically reduced after
      the introduction of the Pap smear test, it still is one of the leading causes of
      death in women worldwide. Additionally, studies that appropriately evaluate the
      risk of developing cervical lesions are needed. Therefore, we investigated
      whether intracellular signaling entropy, which is measured with microarray data,
      could be useful for predicting the risks of developing cervical lesions. We used
      three datasets, GSE63514 (histology), GSE27678 (cytology) and GSE75132 (cytology,
      a prospective study). From the data in GSE63514, the entropy rate was
      significantly increased with disease progression (normal < cervical
      intraepithelial neoplasia, CIN < cancer) (Kruskal-Wallis test, p < 0.0001). From
      the data in GSE27678, similar results (normal < low-grade squamous
      intraepithelial lesions, LSILs < high-grade squamous intraepithelial lesions,
      HSILs <= cancer) were obtained (Kruskal-Wallis test, p < 0.001). From the data in
      GSE75132, the entropy rate tended to be higher in the HPV-persistent groups than
      the HPV-negative group. The group that was destined to progress to CIN 3 or
      higher had a tendency to have a higher entropy rate than the HPV16-positive
      without progression group. In conclusion, signaling entropy was suggested to be
      different for different lesion statuses and could be a useful biomarker for
      predicting the development of cervical intraepithelial neoplasia.

PMID- 28453531
TI  - Structural diversity of Burkholderia pseudomallei lipopolysaccharides affects
      innate immune signaling.
AB  - Burkholderia pseudomallei (Bp) causes the disease melioidosis. The main cause of
      mortality in this disease is septic shock triggered by the host responding to
      lipopolysaccharide (LPS) components of the Gram-negative outer membrane. Bp LPS
      is thought to be a weak inducer of the host immune system. LPS from several
      strains of Bp were purified and their ability to induce the inflammatory
      mediators TNF-alpha and iNOS in murine macrophages at low concentrations was
      investigated. Innate and adaptive immunity qPCR arrays were used to profile
      expression patterns of 84 gene targets in response to the different LPS types.
      Additional qPCR validation confirmed large differences in macrophage response.
      LPS from a high-virulence serotype B strain 576a and a virulent rough central
      nervous system tropic strain MSHR435 greatly induced the innate immune response
      indicating that the immunopathogenesis of these strains is different than in
      infections with strains similar to the prototype strain 1026b. The accumulation
      of autophagic vesicles was also increased in macrophages challenged with highly
      immunogenic Bp LPS. Gene induction and concomitant cytokine secretion profiles of
      human PBMCs in response to the various LPS were also investigated. MALDI-TOF/TOF
      was used to probe the lipid A portions of the LPS, indicating substantial
      structural differences that likely play a role in host response to LPS. These
      findings add to the evolving knowledge of host-response to bacterial LPS, which
      can be used to better understand septic shock in melioidosis patients and in the
      rational design of vaccines.

PMID- 28453532
TI  - Feasibility of computerized working memory training in individuals with
      Huntington disease.
AB  - OBJECTIVES: Huntington disease (HD) is associated with a variety of cognitive
      deficits, with prominent difficulties in working memory (WM). WM deficits are
      notably compromised in early-onset and prodromal HD patients. This study aimed to
      determine the feasibility of a computerized WM training program (Cogmed QM),
      novel to the HD population. METHODS: Nine patients, aged 26-62, with early stage
      HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed
      QM). Training exercises involved the manipulation and storage of verbal and
      visuospatial information, with difficulty adapted as a function of individual
      performance. Neuropsychological testing was conducted before and after training,
      and performance on criterion WM measures (Digit Span and Spatial Span), near
      transfer WM measures (Symbol Span and Auditory WM), and control measures were
      evaluated. Post-training interviews about patient experience were thematically
      analyzed using NVivo software. RESULTS: Seven of nine patients demonstrated
      adherence to the training and completed all sessions within the recommended
      timeframe of 5 weeks. All adherent patients showed improvement on the Cogmed
      tasks as defined by the Improvement Index (M = 22.17, SD = 8.84, range = 13-36).
      All adherent patients reported that they found training helpful (n = 7), and
      almost all felt that their memory improved (n = 6). Participants also expressed
      that the training was difficult, sometimes frustrating, and time consuming.
      CONCLUSIONS: This pilot study provides support for feasibility of computerized WM
      training in early-stage patients with HD. Results suggest that HD patients
      perceive benefits of intensive WM training, though a full-scale and controlled
      intervention project is needed to understand the size of the effect and
      reliability of changes over time. TRIAL REGISTRATION: ClinicalTrials.gov,
      Registry number NCT02926820.

PMID- 28453533
TI  - Periodic cycles of pneumococcal serotypes carried by children before and after 7
      valent pneumococcal conjugate vaccine.
AB  - BACKGROUND: Periodic cycles in the serotype-specific incidence of invasive
      pneumococcal disease have been described but less is known in carriage. METHODS:
      We analyzed serotype carriage prevalence among children 0-6 years old over a 15
      year period that included pre-PCV7 data and a decade of PCV7 use. Mixed
      generalized additive models were used to study periodic cycles and how PCV7
      impacted on them. RESULTS: Pneumococcal carriage data of 7,463 children were
      analyzed. Periodic cycles ranging from 3 to 6 years were observed for PCV7
      serotypes (VT) 14, 19F and 23F and for non-PCV7 types (NVT) 3, 6A, 6C, 11A, and
      NT. An indirect impact of PCV7 on periodic cycles of NVT was observed and could
      be translated in three ways: (i) a higher amplitude in the PCV7 period (serotypes
      3 and 11A), (ii) sustained increase in the prevalence of carriage (serotypes 6C,
      19A and NT) and (iii) an increase in the inter-epidemic period (serotypes 3, 6A
      and NT). An increase in the child's mean age of carriage of VTs 6B, 19F and 23F
      was observed. Serotypes 3, 6C, 11A and 15A became more frequent in ages
      previously associated with carriage of VTs. CONCLUSIONS: Periodic cycles among
      serotypes frequently carried exist and can be modeled. These cycles can be
      perturbed upon introduction of PCVs and can lead to shifts in the mean age of
      carriage. Cyclic re-emergence of VTs can occur in settings with non-universal
      vaccine use. These results should be taken into account when interpreting
      surveillance data on pneumococcal carriage.

PMID- 28453534
TI  - Vitamin and mineral status in chronic fatigue syndrome and fibromyalgia syndrome:
      A systematic review and meta-analysis.
AB  - BACKGROUND: Many chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS)
      patients (35-68%) use nutritional supplements, while it is unclear whether
      deficiencies in vitamins and minerals contribute to symptoms in these patients.
      Objectives were (1) to determine vitamin and mineral status in CFS and FMS
      patients as compared to healthy controls; (2) to investigate the association
      between vitamin and mineral status and clinical parameters, including symptom
      severity and quality of life; and (3) to determine the effect of supplementation
      on clinical parameters. METHODS: The databases PubMed, EMBASE, Web of Knowledge,
      and PsycINFO were searched for eligible studies. Articles published from January
      1st 1994 for CFS patients and 1990 for FMS patients till March 1st 2017 were
      included. Articles were included if the status of one or more vitamins or
      minerals were reported, or an intervention concerning vitamins or minerals was
      performed. Two reviewers independently extracted data and assessed the risk of
      bias. RESULTS: A total of 5 RCTs and 40 observational studies were included in
      the qualitative synthesis, of which 27 studies were included in the meta
      analyses. Circulating concentrations of vitamin E were lower in patients compared
      to controls (pooled standardized mean difference (SMD): -1.57, 95%CI: -3.09, 
      0.05; p = .042). However, this difference was not present when restricting the
      analyses to the subgroup of studies with high quality scores. Poor study quality
      and a substantial heterogeneity in most studies was found. No vitamins or
      minerals have been repeatedly or consistently linked to clinical parameters. In
      addition, RCTs testing supplements containing these vitamins and/or minerals did
      not result in clinical improvements. DISCUSSION: Little evidence was found to
      support the hypothesis that vitamin and mineral deficiencies play a role in the
      pathophysiology of CFS and FMS, and that the use of supplements is effective in
      these patients. REGISTRATION: Study methods were documented in an international
      prospective register of systematic reviews (PROSPERO) protocol, registration
      number: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015032528.

PMID- 28453535
TI  - Plasma amino acids and metabolic profiling of dairy cows in response to a bolus
      duodenal infusion of leucine.
AB  - Leucine (Leu), one of the three branch chain amino acids, acts as a signaling
      molecule in the regulation of overall amino acid (AA) and protein metabolism.
      Leucine is also considered to be a potent stimulus for the secretion of insulin
      from pancreatice beta-cells. Our objective was to study the effects of a duodenal
      bolus infusion of Leu on insulin and glucagon secretion, on plasma AA
      concentrations, and to do a metabolomic profiling of dairy cows as compared to
      infusions with either glucose or saline. Six duodenum-fistulated Holstein cows
      were studied in a replicated 3 * 3 Latin square design with 3 periods of 7 days,
      in which the treatments were applied at the end of each period. The treatments
      were duodenal bolus infusions of Leu (DIL; 0.15 g/kg body weight), glucose (DIG;
      at Leu equimolar dosage) or saline (SAL). On the day of infusion, the treatments
      were duodenally infused after 5 h of fasting. Blood samples were collected at 
      15, 0, 10, 20, 30, 40, 50, 60, 75, 90, 120, 180, 210, 240 and 300 min relative to
      the start of infusion. Blood plasma was assayed for concentrations of insulin,
      glucagon, glucose and AA. The metabolome was also characterized in selected
      plasma samples (i.e. from 0, 50, and 120 min relative to the infusion). Body
      weight, feed intake, milk yield and milk composition were recorded throughout the
      experiment. The Leu infusion resulted in significant increases of Leu in plasma
      reaching 20 and 15-fold greater values than that in DIG and SAL, respectively.
      The elevation of plasma Leu concentrations after the infusion led to a
      significant decrease (P<0.05) in the plasma concentrations of isoleucine, valine,
      glycine, and alanine. In addition, the mean concentrations of lysine, methionine,
      phenylalanine, proline, serine, taurine, threonine, and asparagine across all
      time-points in plasma of DIL cows were reduced (P<0.05) compared with the other
      groups. In contrast to the working hypothesis about an insulinotropic effect of
      Leu, the circulating concentrations of insulin were not affected by Leu. In DIG,
      insulin and glucose concentrations peaked at 30-40 and 40-50 min after the
      infusion, respectively. Insulin concentrations were greater (P<0.05) from 30-40
      min in DIG than DIL and SAL, and glucose was elevated in DIG over DIL and SAL
      from 30-75 min and 40-50 min, respectively. Multivariate metabolomics data
      analysis (principal component analysis and partial least squares discriminant
      analysis) revealed a clear separation when the DIL cows were compared with the
      DIG and SAL cows at 50 and 120 min after the infusion. By using this analysis,
      several metabolites, mainly acylcarnitines, methionine sulfoxide and components
      from the kynurenine pathway were identified as the most relevant for separating
      the treatment groups. These results suggest that Leu regulates the plasma
      concentrations of branched-chain AA, and other AA, apparently by stimulating
      their influx into the cells from the circulation. A single-dose duodenal infusion
      of Leu did not elicit an apparent insulin response, but affected multiple
      intermediary metabolic pathways including AA and energy metabolism by mechanisms
      yet to be elucidated.

PMID- 28453536
TI  - rtfA controls development, secondary metabolism, and virulence in Aspergillus
      fumigatus.
AB  - Invasive aspergillosis by Aspergillus fumigatus is a leading cause of infection
      related mortality in immune-compromised patients. In order to discover potential
      genetic targets to control A. fumigatus infections we characterized rtfA, a gene
      encoding a putative RNA polymerase II transcription elongation factor-like
      protein. Our recent work has shown that the rtfA ortholog in the model fungus
      Aspergillus nidulans regulates morphogenesis and secondary metabolism. The
      present study on the opportunistic pathogen A. fumigatus rtfA gene revealed that
      this gene influences fungal growth and conidiation, as well as production of the
      secondary metabolites tryptoquivaline F, pseurotin A, fumiquinazoline C,
      festuclavine, and fumigaclavines A, B and C. Additionally, rtfA influences
      protease activity levels, the sensitivity to oxidative stress and adhesion
      capacity, all factors important in pathogenicity. Furthermore, rtfA was shown to
      be indispensable for normal virulence using Galleria mellonella as well as murine
      infection model systems.

PMID- 28453537
TI  - An efficient and robust MRI-guided radiotherapy planning approach for targeting
      abdominal organs and tumours in the mouse.
AB  - INTRODUCTION: Preclinical CT-guided radiotherapy platforms are increasingly used
      but the CT images are characterized by poor soft tissue contrast. The aim of this
      study was to develop a robust and accurate method of MRI-guided radiotherapy (MR
      IGRT) delivery to abdominal targets in the mouse. METHODS: A multimodality cradle
      was developed for providing subject immobilisation and its performance was
      evaluated. Whilst CT was still used for dose calculations, target identification
      was based on MRI. Each step of the radiotherapy planning procedure was validated
      initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal
      adrenal glands with a size-matched collimated beam was performed. Additionally,
      the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of
      pancreatic ductal adenocarcinoma were used to demonstrate the applicability of
      our methods for the accurate delivery of radiation to CT-invisible abdominal
      tumours. RESULTS: The BANG gel phantoms demonstrated a targeting efficiency error
      of 0.56 +/- 0.18 mm. The in vivo stability tests of body motion during MR-IGRT
      and the associated cradle transfer showed that the residual body movements are
      within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal
      glands with a size-matched collimated beam was confirmed by gammaH2AX staining.
      Regression in tumour volume was observed almost immediately post MR-IGRT in the
      neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally,
      MR-IGRT in the KPC model facilitated precise contouring and comparison of
      different treatment plans and radiotherapy dose distributions not only to the
      intra-abdominal tumour but also to the organs at risk. CONCLUSION: This is, to
      our knowledge, the first study to demonstrate preclinical MR-IGRT in intra
      abdominal organs. The proposed MR-IGRT method presents a state-of-the-art
      solution to enabling robust, accurate and efficient targeting of extracranial
      organs in the mouse and can operate with a sufficiently high throughput to allow
      fractionated treatments to be given.

PMID- 28453538
TI  - Variation of iron redox kinetics and its relation with molecular composition of
      standard humic substances at circumneutral pH.
AB  - Oxidation and reduction kinetics of iron (Fe) and proportion of steady-state
      Fe(II) concentration relative to total dissolved Fe (steady-state Fe(II)
      fraction) were investigated in the presence of various types of standard humic
      substances (HS) with particular emphasis on the photochemical and thermal
      reduction of Fe(III) and oxidation of Fe(II) by dissolved oxygen (O2) and
      hydrogen peroxide (H2O2) at circumneutral pH (pH 7-8). Rates of Fe(III) reduction
      were spectrophotometrically determined by a ferrozine method under the simulated
      sunlight and dark conditions, whereas rates of Fe(II) oxidation were examined in
      air-saturated solution using luminol chemiluminescence technique. The reduction
      and oxidation rate constants were determined to substantially vary depending on
      the type of HS. For example, the first-order rate constants varied by up to 10
      fold for photochemical reduction and 7-fold for thermal reduction. The degree of
      variation in Fe(II) oxidation was larger for the H2O2-mediated reaction compared
      to the O2-mediated reaction (e.g., 15- and 3-fold changes for the former and
      latter reactions, respectively, at pH 8). The steady-state Fe(II) fraction under
      the simulated sunlight indicated that the Fe(II) fraction varies by up to 12
      fold. The correlation analysis indicated that variation of Fe(II) oxidation is
      significantly associated with aliphatic content of HS, suggesting that Fe(II)
      complexation by aliphatic components accelerates Fe(II) oxidation. The reduction
      rate constant and steady-state Fe(II) fractions in the presence of sunlight had
      relatively strong positive relations with free radical content of HS, possibly
      due to the reductive property of radical semiquinone in HS. Overall, the findings
      in this study indicated that the Fe reduction and oxidation kinetics and
      resultant Fe(II) formation are substantially influenced by chemical properties of
      HS.

PMID- 28453539
TI  - Fetal hemoglobin in umbilical cord blood in preeclamptic and normotensive
      pregnancies: A cross-sectional comparative study.
AB  - Preeclampsia (PE) is associated with increased fetal hemoglobin (HbF) in the
      maternal circulation but its source is unknown. To investigate whether excessive
      HbF is produced in the placenta or the fetus, the concentration of HbF (cHbF) in
      the arterial and venous umbilical cord blood (UCB) was compared in 15825
      normotensive and 444 PE pregnancies. The effect of fetal gender on cHbF was also
      evaluated in both groups. Arterial and venous UCB sampled immediately after birth
      at 36-42 weeks of gestation were analyzed for total Hb concentration (ctHb) (g/L)
      and HbF% using a Radiometer blood gas analyzer. Non-parametric tests were used
      for statistical comparison and P values < 0.05 were considered significant. Our
      results indicated higher cHbF in venous compared to arterial UCB in both
      normotensive (118.90 vs 117.30) and PE (126.75 vs 120.12) groups. In PE compared
      to normotensive pregnancies, a significant increase was observed in arterial and
      venous ctHb (171.00 vs 166.00 and 168.00 vs 163.00, respectively) while cHbF was
      only significantly increased in venous UCB (126.75 vs 118.90). The pattern was
      similar in both genders. These results indicate a substantial placental
      contribution to HbF levels in UCB, which increases in PE and is independent of
      fetal gender, suggesting the elevated cHbF evident in PE results from placental
      dysfunction.

PMID- 28453540
TI  - Pre- and posttreatment with hydrogen sulfide prevents ventilator-induced lung
      injury by limiting inflammation and oxidation.
AB  - Although essential in critical care medicine, mechanical ventilation often
      results in ventilator-induced lung injury. Low concentrations of hydrogen sulfide
      have been proven to have anti-inflammatory and anti-oxidative effects in the
      lung. The aim of this study was to analyze the kinetic effects of pre- and
      posttreatment with hydrogen sulfide in order to prevent lung injury as well as
      inflammatory and oxidative stress upon mechanical ventilation. Mice were either
      non-ventilated or mechanically ventilated with a tidal volume of 12 ml/kg for 6
      h. Pretreated mice inhaled hydrogen sulfide in low dose for 1, 3, or 5 h prior to
      mechanical ventilation. Posttreated mice were ventilated with air followed by
      ventilation with hydrogen sulfide in various combinations. In addition, mice were
      ventilated with air for 10 h, or with air for 5 h and subsequently with hydrogen
      sulfide for 5 h. Histology, interleukin-1beta, neutrophil counts, and reactive
      oxygen species formation were examined in the lungs. Both pre-and posttreatment
      with hydrogen sulfide time-dependently reduced or even prevented edema formation,
      gross histological damage, neutrophil influx and reactive oxygen species
      production in the lung. These results were also observed in posttreatment, when
      the experimental time was extended and hydrogen sulfide administration started as
      late as after 5 h air ventilation. In conclusion, hydrogen sulfide exerts lung
      protection even when its application is limited to a short or delayed period. The
      observed lung protection is mediated by inhibition of inflammatory and oxidative
      signaling.

PMID- 28453541
TI  - The real-world effectiveness and safety of fingolimod in relapsing-remitting
      multiple sclerosis patients: An observational study.
AB  - Fingolimod approval was based mainly on two clinical trials, FREEDOMS and
      TRANSFORMS, which demonstrated the efficacy and safety of fingolimod in patients
      with multiple sclerosis (MS). We present an observational study that validates
      these trials findings in a real-world setting, whereby the effectiveness and
      safety of fingolimod was assessed in Seville's' (Spain) clinical practice. This
      retrospective study in MS patients assessed effectiveness (relapses, EDSS,
      gadolinium-enhancing T1 and new/enlarged T2-weighted lesions): total cohort (n =
      249) and stratified according to prior treatment (glatiramer acetate/interferon
      beta-1 [immunomodulator], natalizumab, naive), gender, basal EDSS score, basal
      Gd+ lesions, ARR prior to treatment, age at treatment initiation and number of
      prior treatments. A multivariante model was used to assess the ARR with baseline
      characteristics. The safety profile (adverse events [AEs]) was also described.
      Fingolimod reduced the annualized relapse rate (ARR) by 75%, 67% and 85% in the
      total cohort, patients previously treated with immunomodulatory and naive
      patients (p<0.0001 all cases). However, patients previously treated with
      natalizumab kept a constant ARR. The ARR results and the consequent increase in
      the proportion of relapse-free patients were independent of the age at treatment
      initiation, number of prior treatments, gender and basal Gd+ lesions. Although
      fingolimod was effective regardless the basal EDSS score and ARR prior to
      fingolimod treatment, better outcomes were observed in patients with basal EDSS
      score <3 (0.2 vs. 0.4; p = 0.0244) and ARR >= 2 prior to fingolimod treatment (p
      = 0.0338). Only the basal EDSS score was association with ARR in the first 24
      months of fingolimod treatment in the multivariante model (p = 0.0439). The
      cumulative probability of disability progression was 20% (month-24) in the total
      cohort, and was independent from prior treatment, age at treatment initiation,
      number of prior treatments, gender, basal EDSS score, basal Gd+ lesions and ARR
      prior to treatment. The real-world fingolimod benefits observed in this study
      seem to be similar than those observed in previous clinical trials.

PMID- 28453542
TI  - Phospholipid profiling of plasma from GW veterans and rodent models to identify
      potential biomarkers of Gulf War Illness.
AB  - Gulf War Illness (GWI), which affects at least one fourth of the 700,000 veterans
      deployed to the Gulf War (GW), is characterized by persistent and heterogeneous
      symptoms, including pain, fatigue and cognitive problems. As a consequence, this
      illness remains difficult to diagnose. Rodent models have been shown to exhibit
      different symptomatic features of GWI following exposure to particular GW agents
      (e.g. pyridostigmine bromide, permethrin and DEET) and/or stress. Preclinical
      analyses have shown the activation of microglia and astroglia as a pathological
      hallmark in these mouse and rat models. Although much has been learned in recent
      years from these different rodent models and independent clinical studies,
      characterization studies to identify overlapping features of GWI in animals and
      humans have been missing. Thus, we aimed to identify biomarkers that co-occur in
      the plasma of rodent models of GWI and human GWI patients. We observed increases
      of multiple phospholipid (PL) species across all studied cohorts. Furthermore,
      these data suggested dysfunction within ether and docosahexaenoic acid and
      arachidonic acid containing PL species in relation to GWI. As these PL species
      play a role in inflammatory processes, these findings suggest a possible role for
      inflammatory imbalance in GWI. Overall, we show that the peripheral lipid
      disturbances are present both in human GWI patients and in the preclinical rodent
      models of GWI, highlighting the importance of lipidomics as a potential platform
      for further biomarker discovery and supporting the value of GW agent exposed
      models of GWI.

PMID- 28453543
TI  - Altered resting-state intra- and inter- network functional connectivity in
      patients with persistent somatoform pain disorder.
AB  - Patients with persistent somatoform pain disorder (PSPD) usually experience
      various functional impairments in pain, emotion, and cognition, which cannot be
      fully explained by a physiological process or a physical disorder. However, it is
      still not clear for the mechanism underlying the pathogenesis of PSPD. The
      present study aimed to explore the intra- and inter-network functional
      connectivity (FC) differences between PSPD patients and healthy controls (HCs).
      Functional magnetic resonance imaging (fMRI) was performed in 13 PSPD patients
      and 23 age- and gender-matched HCs. We used independent component analysis on
      resting-state fMRI data to calculate intra- and inter-network FCs, and we used
      the two-sample t-test to detect the FC differences between groups. Spearman
      correlation analysis was employed to evaluate the correlations between FCs and
      clinical assessments. As compared to HCs, PSPD patients showed decreased
      coactivations in the right superior temporal gyrus within the anterior default
      mode network and the anterior cingulate cortex within the salience network, and
      increased coactivations in the bilateral supplementary motor areas within the
      sensorimotor network and both the left posterior cingulate cortex and the medial
      prefrontal cortex within the anterior default-mode network. In addition, we found
      that the PSPD patients showed decreased FNCs between sensorimotor network and
      audio network as well as visual network, between default-mode network and
      executive control network as well as audio network and between salience network
      and executive control network as well as right frontoparietal network, and
      increased FNCs between sensorimotor network and left frontoparietal network,
      salience network as well as cerebellum network, which were negatively correlated
      with the clinical assessments in PSPD patients. Our findings suggest that PSPD
      patients experience large-scale reorganization at the level of the functional
      networks, which suggests a possible mechanism underlying the pathogenesis of
      PSPD.

PMID- 28453544
TI  - Predicting herbivore faecal nitrogen using a multispecies near-infrared
      reflectance spectroscopy calibration.
AB  - Optimal management of free-ranging herbivores requires the accurate assessment of
      an animal's nutritional status. For this purpose 'near-infrared reflectance
      spectroscopy' (NIRS) is very useful, especially when nutritional assessment is
      done through faecal indicators such as faecal nitrogen (FN). In order to perform
      an NIRS calibration, the default protocol recommends starting by generating an
      initial equation based on at least 50-75 samples from the given species. Although
      this protocol optimises prediction accuracy, it limits the use of NIRS with rare
      or endangered species where sample sizes are often small. To overcome this
      limitation we tested a single NIRS equation (i.e., multispecies calibration) to
      predict FN in herbivores. Firstly, we used five herbivore species with highly
      contrasting digestive physiologies to build monospecies and multispecies
      calibrations, namely horse, sheep, Pyrenean chamois, red deer and European
      rabbit. Secondly, the equation accuracy was evaluated by two procedures using:
      (1) an external validation with samples from the same species, which were not
      used in the calibration process; and (2) samples from different ungulate species,
      specifically Alpine ibex, domestic goat, European mouflon, roe deer and cattle.
      The multispecies equation was highly accurate in terms of the coefficient of
      determination for calibration R2 = 0.98, standard error of validation SECV =
      0.10, standard error of external validation SEP = 0.12, ratio of performance to
      deviation RPD = 5.3, and range error of prediction RER = 28.4. The accuracy of
      the multispecies equation to predict other herbivore species was also
      satisfactory (R2 > 0.86, SEP < 0.27, RPD > 2.6, and RER > 8.1). Lastly, the
      agreement between multi- and monospecies calibrations was also confirmed by the
      Bland-Altman method. In conclusion, our single multispecies equation can be used
      as a reliable, cost-effective, easy and powerful analytical method to assess FN
      in a wide range of herbivore species.

PMID- 28453545
TI  - The impact of gender difference on clinical and echocardiographic outcomes in
      patients with heart failure after cardiac resynchronization therapy: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Cardiac resynchronization therapy(CRT) has been recommended as a
      standard treatment for patients with advanced heart failure. However, some
      studies have reported different clinical and echocardiographic outcomes between
      male and female patients who received CRT. This Meta-analysis is to determine
      whether gender difference has any significant impact on clinical and
      echocardiographic outcomes in patients with heart failure after CRT. METHODS AND
      RESULTS: PubMed, Embase, and the Cochrane library database were searched. A total
      of 149,259 patients in 11 studies were identified. Our analysis demonstrated that
      women showed lower all-cause mortality than men after CRT (odds ratio[OR] 0.50,
      95% confidence interval [CI] 0.36 to 0.70). No significant difference was
      observed in the increment of New York Heart Association (NYHA) functional
      class(standard mean difference[SMD] -0.07,95% CI -0.15 to 0.01), 6-minitue walk
      distance (6-MWD) (SMD -0.05, 95% CI -0.07 to 0.17), and quality of life (QoL)
      (SMD -0.10, 95% CI -0.23 to 0.03). With respect to the echocardiographic
      parameters, women exhibited statistically significant improvement in left
      ventricular ejection fraction (LVEF) (SMD 0.25,95% CI 0.07 to 0.43), and
      decrement of left ventricular end diastolic diameter (LVEDD) (SMD -0.27, 95% CI 
      0.39 to -0.25) as compared with men. No significant difference was observed in
      left ventricular end diastolic volume (LVEDV) (SMD -0.08, 95% CI -0.28 to 0.08)
      and left ventricular end systolic volume (LVESV) (SMD -0.16, 95% CI -0.40 to
      0.09) between men and women. CONCLUSION: Women seem to obtain greater benefits
      from CRT both in clinical and echocardiographic outcomes compared with men. But
      as this gender superiority could be observed only during long-term follow-up
      periods, further studies are needed to elucidate exact reasons for this
      phenomenon.

PMID- 28453546
TI  - Improved approximation of spatial light distribution.
AB  - The rapid worldwide evolution of LEDs as light sources has brought new
      challenges, which means that new methods are needed and new algorithms have to be
      developed. Since the majority of LED luminaries are of the multi-source type,
      established methods for the design of light engines cannot be used in the design
      of LED light engines. This is because in the latter case what is involved is not
      just the design of a good reflector or projector lens, but the design of several
      lenses which have to work together in order to achieve satisfactory results.
      Since lenses can also be bought off the shelf from several manufacturers, it
      should be possible to combine together different off the shelf lenses in order to
      design a good light engine. However, with so many different lenses to choose
      from, it is almost impossible to find an optimal combination by hand, which means
      that some optimization algorithms need to be applied. In order for them to work
      properly, it is first necessary to describe the input data (i.e. spatial light
      distribution) in a functional form using as few as possible parameters. In this
      paper the focus is on the approximation of the input data, and the implementation
      of the well-known mathematical procedure for the separation of linear and
      nonlinear parameters, which can provide a substantial increase in performance.

PMID- 28453548
TI  - Self-feedbacks determine the sustainability of human interventions in eco-social
      complex systems: Impacts on biodiversity and ecosystem health.
AB  - Several administrative polices have been implemented in order to reduce the
      negative impacts of fishing on natural ecosystems. Four eco-social models with
      different levels of complexity were constructed, which represent the seaweed
      harvest in central-northern Chile under two different regimes, Management and
      Exploitation Areas for Benthic Resources (MAEBRs) and Open Access Areas (OAAs).
      The dynamics of both regimes were analyzed using the following theoretical
      frameworks: (1) Loop Analysis, which allows the local stability or sustainability
      of the models and scenarios to be assessed; and (2) Hessian's optimization
      procedure of a global fishery function (GFF) that represents each dynamics of
      each harvest. The results suggest that the current fishing dynamics in MAEBRs are
      not sustainable unless the market demand presents some type of control (i.e.
      taxes). Further, the results indicated that if the demand changes to a self
      negative feedback (self-control) in MAEBRs, the stability is increased and,
      simultaneously, a relative maximum for the GFF is reached. Contrarily, the
      sustainability of the model/system representing the harvest (principally by
      cutting plants) in OAAs is not reached. The implementation of an "ecological" tax
      for intensive artisanal fisheries with low operational cost is proposed. The
      network analysis developed here is proposed as a general strategy for studying
      the effects of human interventions in marine coastal ecosystems under transient
      (short-term) dynamics.

PMID- 28453547
TI  - A systematic review of hybrid brain-computer interfaces: Taxonomy and usability
      perspectives.
AB  - A new Brain-Computer Interface (BCI) technique, which is called a hybrid BCI, has
      recently been proposed to address the limitations of conventional single BCI
      system. Although some hybrid BCI studies have shown promising results, the field
      of hybrid BCI is still in its infancy and there is much to be done. Especially,
      since the hybrid BCI systems are so complicated and complex, it is difficult to
      understand the constituent and role of a hybrid BCI system at a glance. Also, the
      complicated and complex systems make it difficult to evaluate the usability of
      the systems. We systematically reviewed and analyzed the current state-of-the-art
      hybrid BCI studies, and proposed a systematic taxonomy for classifying the types
      of hybrid BCIs with multiple taxonomic criteria. After reviewing 74 journal
      articles, hybrid BCIs could be categorized with respect to 1) the source of brain
      signals, 2) the characteristics of the brain signal, and 3) the characteristics
      of operation in each system. In addition, we exhaustively reviewed recent
      literature on usability of BCIs. To identify the key evaluation dimensions of
      usability, we focused on task and measurement characteristics of BCI usability.
      We classified and summarized 31 BCI usability journal articles according to task
      characteristics (type and description of task) and measurement characteristics
      (subjective and objective measures). Afterwards, we proposed usability dimensions
      for BCI and hybrid BCI systems according to three core-constructs: Satisfaction,
      effectiveness, and efficiency with recommendations for further research. This
      paper can help BCI researchers, even those who are new to the field, can easily
      understand the complex structure of the hybrid systems at a glance.
      Recommendations for future research can also be helpful in establishing research
      directions and gaining insight in how to solve ergonomics and HCI design issues
      surrounding BCI and hybrid BCI systems by usability evaluation.

PMID- 28453549
TI  - Idiosyncratic recognition of UUG/UUA codons by modified nucleoside 5
      taurinomethyluridine, taum5U present at 'wobble' position in anticodon loop of
      tRNALeu: A molecular modeling approach.
AB  - Lack of naturally occurring modified nucleoside 5-taurinomethyluridine (taum5U)
      at the 'wobble' 34th position in tRNALeu causes mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The taum5U34
      specifically recognizes UUG and UUA codons. Structural consequences of taum5U34
      to read cognate codons have not been studied so far in detail at the atomic
      level. Hence, 50ns multiple molecular dynamics (MD) simulations of various
      anticodon stem loop (ASL) models of tRNALeu in presence and absence of taum5U34
      along with UUG and UUA codons were performed to explore the dynamic behaviour of
      taum5U34 during codon recognition process. The MD simulation results revealed
      that taum5U34 recognizes G/A ending codons by 'wobble' as well as a novel
      'single' hydrogen bonding interactions. RMSD and RMSF values indicate the
      comparative stability of the ASL models containing taum5U34 modification over the
      other models, lacking taum5U34. Another MD simulation study of 55S mammalian
      mitochondrial rRNA with tRNALeu showed crucial interactions between the A-site
      residues, A918, A919, G256 and codon-anticodon bases. Thus, these results could
      improve our understanding about the decoding efficiency of human mt tRNALeu with
      taum5U34 to recognize UUG and UUA codons.

PMID- 28453550
TI  - Selective mitochondrial DNA degradation following double-strand breaks.
AB  - Mitochondrial DNA (mtDNA) can undergo double-strand breaks (DSBs), caused by
      defective replication, or by various endogenous or exogenous sources, such as
      reactive oxygen species, chemotherapeutic agents or ionizing radiations. MtDNA
      encodes for proteins involved in ATP production, and maintenance of genome
      integrity following DSBs is thus of crucial importance. However, the mechanisms
      involved in mtDNA maintenance after DSBs remain unknown. In this study, we
      investigated the consequences of the production of mtDNA DSBs using a human
      inducible cell system expressing the restriction enzyme PstI targeted to
      mitochondria. Using this system, we could not find any support for DSB repair of
      mtDNA. Instead we observed a loss of the damaged mtDNA molecules and a severe
      decrease in mtDNA content. We demonstrate that none of the known mitochondrial
      nucleases are involved in the mtDNA degradation and that the DNA loss is not due
      to autophagy, mitophagy or apoptosis. Our study suggests that a still
      uncharacterized pathway for the targeted degradation of damaged mtDNA in a
      mitophagy/autophagy-independent manner is present in mitochondria, and might
      provide the main mechanism used by the cells to deal with DSBs.

PMID- 28453551
TI  - Associations between cytokine gene polymorphisms and susceptibility to
      Helicobacter pylori infection and Helicobacter pylori related gastric cancer,
      peptic ulcer disease: A meta-analysis.
AB  - OBJECTIVES: The aim of this study is to clarify the associations between IL
      1B31C/T, IL-1B-511C/T, IL-8-251T/A gene polymorphisms and the risk of
      Helicobacter pylori (H. pylori) infection together with H. pylori-related gastric
      cancer (GC), peptic ulcer disease (PUD). METHODS: All eligible literature
      published up to July 2016 were identified by searching Pubmed, Embase, Web of
      Science and CNKI. Pooled odds ratio (OR) and 95% confidence interval (95% CI)
      were calculated using a fixed or random effects model. RESULTS: 29 case-control
      studies were eligible, and each of them may focus on more than one gene
      polymorphism. Ultimately, there were 21 studies (3159 cases and 2816 controls)
      for IL-1B-31C/T, 16 studies (2486 cases and 1989 controls) for IL-1B-511C/T
      polymorphisms, 9 studies (1963 cases and 1205 controls) for IL-8-251T/A
      polymorphisms. Overall, an increased risk of H. pylori infection was found for IL
      1B-31C/T polymorphisms in total population [OR = 1.134, 95%CI = 1.008-1.275 for
      recessive model; OR = 1.145, 95%CI = 1.007-1.301 for TT vs CC model]. While, for
      IL-1B-511C/T and IL8-251T/A polymorphisms, no evidence indicated that they were
      associated with the risk of H. pylori infection in all genetic models.
      Furthermore, we found an increased risk of H. pylori-related GC with IL-1B-511C/T
      polymorphisms [OR = 1.784, 95%CI = 1.289-2.469 for recessive model; OR = 1.772,
      95%CI = 1.210-2.594 for TT vs CC model] and IL8-251A/T polymorphisms [OR = 1.810,
      95%CI = 1.229-2.667 for recessive model; OR = 1.717, 95%CI = 1.143-2.580 for TT
      vs AA model], an increased risk of H. pylori-related PUD with IL8-251T/A
      polymorphisms [OR = 1.364, 95%CI = 1.010-1.843 for recessive model; OR = 1.427,
      95%CI = 1.039-1.959 for AA vs TT model]. CONCLUSIONS: IL-1B-31C/T gene
      polymorphisms might increase H. pylori infection risk. IL-1B-511-C/T and IL-8
      251T/A gene polymorphisms might act as a risk factor to H. pylori-related
      diseases including GC or PUD.

PMID- 28453552
TI  - Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is
      cytotoxic in glioblastoma.
AB  - A small molecule which specifically blocks the interaction of Rictor and mTOR was
      identified utilizing a high-throughput yeast two-hybrid screen and evaluated as a
      potential inhibitor of mTORC2 activity in glioblastoma multiforme (GBM). In
      vitro, CID613034 inhibited mTORC2 kinase activity at submicromolar concentrations
      and in cellular assays specifically inhibited phosphorylation of mTORC2
      substrates, including AKT (Ser-473), NDRG1 (Thr-346) and PKCalpha (Ser-657),
      while having no appreciable effects on the phosphorylation status of the mTORC1
      substrate S6K (Thr-389) or mTORC1-dependent negative feedback loops. CID613034
      demonstrated significant inhibitory effects on cell growth, motility and
      invasiveness in GBM cell lines and sensitivity correlated with relative Rictor or
      SIN1 expression. Structure-activity relationship analyses afforded an inhibitor,
      JR-AB2-011, with improved anti-GBM properties and blocked mTORC2 signaling and
      Rictor association with mTOR at lower effective concentrations. In GBM xenograft
      studies, JR-AB2-011 demonstrated significant anti-tumor properties. These data
      support mTORC2 as a viable therapeutic target in GBM and suggest that targeting
      protein-protein interactions critical for mTORC2 function is an effective
      strategy to achieve therapeutic responses.

PMID- 28453553
TI  - A tool for discovering drug sensitivity and gene expression associations in
      cancer cells.
AB  - The sensitivity of cancer cells to anticancer drugs is a crucial factor for
      developing effective treatments. However, it is still challenging to precisely
      predict the effectiveness of therapeutics in humans within a complex genomic and
      molecular context. We developed an interface which allows the user to rapidly
      explore drug sensitivity and gene expression associations. Predictions for how
      expression of various genes affect anticancer drug activity are available for all
      genes for a set of therapeutics based on data from various cell lines of
      different origin in the Cancer Cell Line Encyclopedia and the Genomics of Drug
      Sensitivity in Cancer projects. Our application makes discovery or validation of
      drug sensitivity and gene expression associations efficient. Effectiveness of
      this tool is demonstrated by multiple known and novel examples.

PMID- 28453554
TI  - Prognostic value of PD-L1 expression in tumor infiltrating immune cells in
      cancers: A meta-analysis.
AB  - Programmed death-ligand 1 (PD-L1) is a promising target of cancer immune therapy.
      It not only expressed in tumor cells (TCs) but also up regulated in tumor
      infiltrating immune cells (TIICs). Although the previous meta-analysis have shown
      that PD-L1 expression in TCs was a valuable biomarker in predicting cancer
      prognosis, but few researches systematic evaluated the association between its
      expression in TIICs and survival of cancer patients. Thus, we performed this meta
      analysis to evaluate the prognostic value of PD-L1 expression in TIICs in
      different types of cancers. Our results are valuable supplements when using PD-L1
      expression to predict the survival of cancer patients and to select the
      beneficial patients from PD-L1 target therapy. PubMed, Embase, Web of Science and
      the Cochrane Central Search Library were used to perform our systematic
      literature search. Overall survival (OS) at 5th years and hazard ratios (HRs)
      were calculated using random effects models. Eighteen studies involving 3674
      patients were included. The median positive rate of PD-L1 staining in TIICs was
      36.37%. PD-L1 positive expression in TIICs related to a lower risk of death (HR =
      0.784, 95%CI: 0.616-0.997, P = 0.047). Subgroup analyses found that PD-L1
      positive expression in TIICs indicated a better prognosis especially in breast
      cancer patients (HR = 0.359, P = 0.041). When using whole tissue section slides,
      or using 'any expression in TIICs' as a cutoff value to assessing the results of
      IHC staining, PD-L1 expression in TIICs had a good prognostic value in cancer
      prognosis (HR = 0.587, P = 0.001 and HR = 0.549, P = 0.002). Our findings
      suggested that PD-L1 expression in TIICs was related to a better survival of
      cancer. The comprehensive evaluation of tumor cells and tumor infiltrating immune
      cells are required when evaluating the effect of PD-L1 expression on prognosis of
      cancer in future research.

PMID- 28453555
TI  - Multi-subunit BCG booster vaccine GamTBvac: Assessment of immunogenicity and
      protective efficacy in murine and guinea pig TB models.
AB  - New innovative vaccines are highly needed to combat the global threat posed by
      tuberculosis. Efficient components-antigens and adjuvants-are crucial for
      development of modern recombinant TB vaccines. This study describes a new vaccine
      (GamTBvac) consisting of two mycobacterial antigen fusions (Ag85A and ESAT6
      CFP10)-with dextran-binding domain immobilized on dextran and mixed with an
      adjuvant consisting of DEAE-dextran core, and with CpG oligodeoxynucleotides
      (TLR9 agonists). GamTBvac and its components were assessed for immunogenicity and
      protective efficacy in GamTBvac-prime/boost and BCG-prime/ GamTBvac-boost in
      murine and guinea pig TB models. Results show that in both infectious models,
      GamTBvac has a strong immunogenicity and significant protective effect against
      Mycobacterium tuberculosis strain H37Rv under aerosol and intravenous challenges.
      GamTBvac showed a particularly strong protective effect as a BCG booster vaccine.

PMID- 28453556
TI  - Characterization of interfragmentary motion associated with common osteosynthesis
      devices for rat fracture healing studies.
AB  - Rat models are widely used in preclinical studies investigating fracture healing.
      The interfragmentary movement at a fracture site is critical to the course of
      healing and therefore demands definition in order to aptly interpret the
      experimental results. Estimation of this movement requires knowledge of the
      fixation stiffness and loading. The characteristic loading for the rat femur has
      been estimated, but the stiffness of fixation used in rat studies has yet to be
      fully described. This study aimed to determine the 6 degree of freedom stiffness
      of four commonly used implants, two external fixators (RatExFix and UlmExFix), a
      locking plate, and a locking intramedullary nail, in all degrees of freedom and
      estimate the interfragmentary movement under specific physiological loads. The
      external fixator systems allow the greatest movement. Mounted 45 degrees 
      anterolateral on the femur, the RatExFix allows an average of 0.88 mm of motion
      in each anatomic direction while the stiffer UlmExFix allows about 0.6 mm of
      motion. The nail is far stiffer than the other implants investigated while the
      plate allows movement of an intermediate magnitude. Both the nail and plate
      demonstrate higher axial than shear stiffness. The relatively large standard
      deviations in external fixator shear motion imply strong dependence on bone axis
      alignment across the gap and the precise orientation of the specimen relative to
      the loading. The smaller standard deviation associated with the nail and plate
      results from improved alignment and minimization of the influence of rotational
      positioning of the specimen due to the reduced implant eccentricity relative to
      the specimen axis. These results show that the interfragmentary movement is
      complex and varies significantly between fixation devices but establishes a
      baseline for the evaluation of the results of different studies.

PMID- 28453557
TI  - Perivascular radiofrequency renal denervation lowers blood pressure and
      ameliorates cardiorenal fibrosis in spontaneously hypertensive rats.
AB  - BACKGROUND: Catheter-based renal denervation (RDN) is a promising approach to
      treat hypertension, but innervation patterns limit the response to endovascular
      RDN and the post-procedural renal artery narrowing or stenosis questions the
      endovascular ablation strategy. This study was performed to investigate the anti
      hypertensive and target organ protective effects of perivascular RDN in
      spontaneously hypertensive rats (SHR). METHODS: SHR and normotensive Wistar-Kyoto
      (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group
      (n = 20) in which rats received bilateral perivascular ablation with
      radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol)
      ablation group (n = 12). The tail-cuff blood pressure was measured before the
      ablation and on day 14 and day 28 after the procedure. The plasma levels of
      creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes
      and protein, and myocardial and glomerular fibrosis were analyzed and compared
      among the groups on day 28 after the procedure. RESULTS: We identified that 2
      watt is the optimal radiofrequency power for perivascular RDN in rats.
      Perivascular radiofrequency and chemical ablation achieved roughly comparable
      blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the
      procedure. Radiofrequency-mediated ablation substantially destroyed the renal
      nerves surrounding the renal arteries of both SHR and WKY without damaging the
      renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme
      marker for postganglionic sympathetic nerves. Additionally, perivascular
      radiofrequency ablation also decreased the plasma catecholamines of SHR.
      Interestingly, both radiofrequency and chemical ablation decreased the myocardial
      and glomerular fibrosis of SHR, while neither increased the plasma creatinine and
      blood urea nitrogen nor affected the urinary excretion of electrolytes and
      protein when compared to sham group. CONCLUSIONS: Radiofrequency-mediated
      perivascular RDN may become a feasible procedure against hypertension, and
      provide similar anti-hypertensive and target organ protective effects as does the
      chemical ablation.

PMID- 28453558
TI  - Tumor-targeted SN38 inhibits growth of early stage non-small cell lung cancer
      (NSCLC) in a KRas/p53 transgenic mouse model.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer death
      worldwide, with a 5-year survival of only ~16%. Potential strategies to address
      NSCLC mortality include improvements in early detection and prevention, and
      development of new therapies suitable for use in patients with early and late
      stage diagnoses. Controlling the growth of early stage tumors could yield
      significant clinical benefits for patients with comorbidities that make them poor
      candidates for surgery: however, many drugs that limit cancer growth are not
      useful in the setting of long-term use or in comorbid patients, because of
      associated toxicities. In this study, we explored the use of a recently described
      small molecule agent, STA-8666, as a potential agent for controlling early stage
      tumor growth. STA-8666 uses a cleavable linker to merge a tumor-targeting moiety
      that binds heat shock protein 90 (HSP90) with the cytotoxic chemical SN38, and
      has been shown to have high efficacy and low toxicity, associated with efficient
      tumor targeting, in preclinical studies using patient-derived and other xenograft
      models for pancreatic, bladder, and small cell lung cancer. Using a genetically
      engineered model of NSCLC arising from induced mutation of KRas and knockout of
      Trp53, we continuously dosed mice with STA-8666 from immediately after tumor
      induction for 15 weeks. STA-8666 significantly slowed the rate of tumor growth,
      and was well tolerated over this extended dosing period. STA-8666 induced DNA
      damage and apoptosis, and reduced proliferation and phosphorylation of the
      proliferation-associated protein ERK1/2, selectively in tumor tissue. In
      contrast, STA-8666 did not affect tumor features, such as degree of vimentin
      staining, associated with epithelial-mesenchymal transition (EMT), or
      downregulate tumor expression of HSP90. These data suggest STA-8666 and other
      similar targeted compounds may be useful additions to control the growth of early
      stage NSCLC in patient populations.

PMID- 28453559
TI  - Evaluation of the reproducibility of amplicon sequencing with Illumina MiSeq
      platform.
AB  - Illumina's MiSeq has become the dominant platform for gene amplicon sequencing in
      microbial ecology studies; however, various technical concerns, such as
      reproducibility, still exist. To assess reproducibility, 16S rRNA gene amplicons
      from 18 soil samples of a reciprocal transplantation experiment were sequenced on
      an Illumina MiSeq. The V4 region of 16S rRNA gene from each sample was sequenced
      in triplicate with each replicate having a unique barcode. The average OTU
      overlap, without considering sequence abundance, at a rarefaction level of 10,323
      sequences was 33.4+/-2.1% and 20.2+/-1.7% between two and among three technical
      replicates, respectively. When OTU sequence abundance was considered, the average
      sequence abundance weighted OTU overlap was 85.6+/-1.6% and 81.2+/-2.1% for two
      and three replicates, respectively. Removing singletons significantly increased
      the overlap for both (~1-3%, p<0.001). Increasing the sequencing depth to 160,000
      reads by deep sequencing increased OTU overlap both when sequence abundance was
      considered (95%) and when not (44%). However, if singletons were not removed the
      overlap between two technical replicates (not considering sequence abundance)
      plateaus at 39% with 30,000 sequences. Diversity measures were not affected by
      the low overlap as alpha-diversities were similar among technical replicates
      while beta-diversities (Bray-Curtis) were much smaller among technical replicates
      than among treatment replicates (e.g., 0.269 vs. 0.374). Higher diversity
      coverage, but lower OTU overlap, was observed when replicates were sequenced in
      separate runs. Detrended correspondence analysis indicated that while there was
      considerable variation among technical replicates, the reproducibility was
      sufficient for detecting treatment effects for the samples examined. These
      results suggest that although there is variation among technical replicates,
      amplicon sequencing on MiSeq is useful for analyzing microbial community
      structure if used appropriately and with caution. For example, including
      technical replicates, removing spurious sequences and unrepresentative OTUs,
      using a clustering method with a high stringency for OTU generation, estimating
      treatment effects at higher taxonomic levels, and adapting the unique molecular
      identifier (UMI) and other newly developed methods to lower PCR and sequencing
      error and to identify true low abundance rare species all can increase
      reproducibility.

PMID- 28453560
TI  - Caspase polymorphisms and prognosis of hepatocellular carcinoma.
AB  - The aim of our study was to determine the impact of genetic polymorphisms in the
      caspase (CASP) genes on prognosis of hepatocellular carcinoma (HCC). We genotyped
      7 potentially functional polymorphisms in CASP3, CASP7, CASP8, CASP9, CASP10
      genes in 362 HCC patients of receiving surgical resection of HCC tumor. The
      associations of genotype and haplotype with overall survival (OS) and disease
      free survival (DFS) were analyzed by using the Cox proportional hazards model. We
      found that the CASP9 rs4645981 C allele was significantly associated with
      positive effect on DFS (P = 0.011 and 0.016 for CT+CC vs. TT in univariate and
      multivariate analysis, respectively), CT genotype was associated with a better OS
      of HCC than the TT genotype both in univariate and multivariate analysis (P =
      0.048 and 0.041, respectively). Moreover, the CASP3 rs2705897 GT genotype showed
      marginally significant association with decreased OS and DFS, compared with the
      GG genotype. One haplotype TT/TG in CASP3 (constructed by rs12108497 T>C and
      rs2705897 T>G) was significantly associated with decreased OS and DFS, compared
      to the common haplotype TT/TT both in univariate analysis (P = 0.021 and 0.026,
      respectively) and multivariate analysis (P = 0.025 and 0.030, respectively). The
      haplotype GT/GT in CASP9 (constructed by rs4645978 A>G and rs4645981 C>T) was
      significantly associated with decreased DFS both in univariate and multivariate
      analysis (P = 0.012 and 0.010, respectively). In conclusion, the CASP9 rs4645981
      polymorphism, CASP3 and CASP9 haplotypes may be useful prognosis markers for HCC
      patients with surgical resection of tumor.

PMID- 28453561
TI  - A WebGIS platform for the monitoring of Farm Animal Genetic Resources (GENMON).
AB  - BACKGROUND: In 2007, the Food and Agriculture Organization of the United Nations
      (FAO) initiated the Global plan of action for Farm Animal Genetic Resources
      (FAnGR). The main goal of this plan is to reduce further loss of genetic
      diversity in farm animals, so as to protect and promote the diversity of farm
      animal resources. An important step to reach this goal is to monitor and
      prioritize endangered breeds in the context of conservation programs.
      METHODOLOGY/WEB PORTAL IMPLEMENTATION: The GENMON WebGIS platform is able to
      monitor FAnGR and to evaluate the degree of endangerment of livestock breeds. The
      system takes into account pedigree and introgression information, the
      geographical concentration of animals, the cryo-conservation plan and the
      sustainability of breeding activities based on socio-economic data as well as
      present and future land use conditions. A multi-criteria decision tool supports
      the aggregation of the multi-thematic indices mentioned above using the MACBETH
      method, which is based on a weighted average using satisfaction thresholds.
      GENMON is a monitoring tool to reach subjective decisions made by a government
      agency. It relies on open source software and is available at
      http://lasigsrv2.epfl.ch/genmon-ch. RESULTS/SIGNIFICANCE: GENMON allows users to
      upload pedigree-information (animal ID, parents, birthdate, sex, location and
      introgression) from a specific livestock breed and to define species and/or
      region-specific weighting parameters and thresholds. The program then completes a
      pedigree analysis and derives several indices that are used to calculate an
      integrated score of conservation prioritization for the breeds under
      investigation. The score can be visualized on a geographic map and allows a fast,
      intuitive and regional identification of breeds in danger. Appropriate
      conservation actions and breeding programs can thus be undertaken in order to
      promote the recovery of the genetic diversity in livestock breeds in need. The
      use of the platform is illustrated by means of an example based on three local
      livestock breeds from different species in Switzerland.

PMID- 28453562
TI  - Associations of women's position in the household and food insecurity with family
      planning use in Nepal.
AB  - BACKGROUND: Women in Nepal have low status, especially younger women in co
      resident households. Nepal also faces high levels of household food insecurity
      and malnutrition, and stagnation in uptake of modern family planning methods.
      OBJECTIVE: This study aims to understand if household structure and food
      insecurity interact to influence family planning use in Nepal. METHODS: Using
      data on married, non-pregnant women aged 15-49 with at least one child from the
      Nepal 2011 Demographic and Health Survey (N = 7,460), we explore the relationship
      between women's position in the household, food insecurity as a moderator, and
      family planning use, using multi-variable logistic regressions. We adjust for
      household and individual factors, including other status-related variables.
      RESULTS: In adjusted models, living in a food insecure household and co-residing
      with in-laws either with no other daughter-in-laws or as the eldest or youngest
      daughter-in-law (compared to not-co-residing with in-laws) are all associated
      with lower odds of family planning use. In the interaction model, younger-sisters
      in-law and women co-residing with no sisters-in-law in food insecure households
      have the lowest odds of family planning use. CONCLUSION: This study shows that
      household position is associated with family planning use in Nepal, and that food
      insecurity modifies these associations-highlighting the importance of considering
      both factors in understanding reproductive health care use in Nepal. Policies and
      programs should focus on the multiple pathways through which food insecurity
      impacts women's reproductive health, including focusing on women with the lowest
      status in households.

PMID- 28453563
TI  - Reproductive success is energetically linked to foraging efficiency in Antarctic
      fur seals.
AB  - The efficiency with which individuals extract energy from their environment
      defines their survival and reproductive success, and thus their selective
      contribution to the population. Individuals that forage more efficiently (i.e.,
      when energy gained exceeds energy expended) are likely to be more successful at
      raising viable offspring than individuals that forage less efficiently. Our goal
      was to test this prediction in large long-lived mammals under free-ranging
      conditions. To do so, we equipped 20 lactating Antarctic fur seals (Arctocephalus
      gazella) breeding on Kerguelen Island in the Southern Ocean with tags that
      recorded GPS locations, depth and tri-axial acceleration to determine at-sea
      behaviours and detailed time-activity budgets during their foraging trips. We
      also simultaneously measured energy spent at sea using the doubly-labeled water
      (DLW) method, and estimated the energy acquired while foraging from 1) type and
      energy content of prey species present in scat remains, and 2) numbers of prey
      capture attempts determined from head acceleration. Finally, we followed the
      growth of 36 pups from birth until weaning (of which 20 were the offspring of our
      20 tracked mothers), and used the relative differences in body mass of pups at
      weaning as an index of first year survival and thus the reproductive success of
      their mothers. Our results show that females with greater foraging efficiencies
      produced relatively bigger pups at weaning. These mothers achieved greater
      foraging efficiency by extracting more energy per minute of diving rather than by
      reducing energy expenditure. This strategy also resulted in the females spending
      less time diving and less time overall at sea, which allowed them to deliver
      higher quality milk to their pups, or allowed their pups to suckle more
      frequently, or both. The linkage we demonstrate between reproductive success and
      the quality of individuals as foragers provides an individual-based quantitative
      framework to investigate how changes in the availability and accessibility of
      prey can affect fitness of animals.

PMID- 28453564
TI  - The influence of climatic variation and density on the survival of an insular
      passerine Zosterops lateralis.
AB  - Understanding the influence of environmental factors on population dynamics is
      fundamental to many areas in biology. Survival is a key factor of population
      biology, as it is thought to be the predominant driver of growth in long-lived
      passerines, which can be influenced by both biotic and abiotic environmental
      conditions. We used mark-recapture methods and generalized linear mixed models to
      test the influence of density and climatic variation, measured at a regional and
      local scale (Southern Oscillation Index [SOI] and rainfall, respectively), on
      seasonal variation in survival rates of an insular population of Silvereyes
      (Zosterops lateralis chlorocephalus), during a 15-year study period, off the east
      coast of Australia. We found overall high survival rates for adults and juveniles
      (81% and 59%, respectively). Local scale climate (i.e. rainfall) and density were
      the principal environmental factors influencing their survival, both with a
      negative relationship. A significant interactive effect of density and rainfall
      influenced survival as they both increased. However, survival remained low when
      density was at it highest, independent of the amount of rainfall. Nestling
      survival was negatively influenced by rainfall and density, positively by SOI,
      and chicks that hatched later in the breeding season had higher survival rates.
      The regional scale climate variable (i.e. SOI) did not explain survival rates as
      strongly as rainfall in any age class. Our results contribute to the
      understanding of insular avian population dynamics and the differential effects
      of environmental factors across age classes. Climatic predictions expect El Nino
      events to increase, meaning dryer conditions in eastern Australia, potentially
      increasing Silvereye survival across age classes. However, the long-term effect
      of lower rainfall on food availability is unknown; consequently, the outcome of
      lower rainfall on Silvereye survival rates is uncertain.

PMID- 28453565
TI  - Risk factors and outcome of Shigella encephalopathy in Bangladeshi children.
AB  - BACKGROUND: Although, Shigella encephalopathy, a serious extra-intestinal
      complication of shigellosis, significantly increases the risks of death, data are
      very limited on predicting factors particularly related to electrolyte profiles
      in children below five years of age with Shigella encephalopathy. Our objective
      was to determine the clinical as well as laboratory predicting factors and
      outcome of children with Shigella encephalopathy. METHODOLOGY/PRINCIPAL FINDINGS:
      In this unmatched case-control design, children aged 2-59 months having a
      positive stool culture for Shigella and who had their serum electrolytes been
      done from July 2012 to June 2015 were studied. Children with Shigella
      encephalopathy, defined as having abnormal mentation, constituted the cases, and
      those without encephalopathy constituted the controls. During the study period,
      we identified a total of 541 children less than five years of age, who had
      Shigella in their stool culture. Only 139 children fulfilled the study criteria
      and among them 69 were cases and 70 were controls. The cases more often had fatal
      outcome compared to the controls (7% vs. 0%, P = 0.02). In logistic regression
      analysis, the cases were independently associated with shorter duration (1.2 +/-
      0.4 days) of diarrhea prior to admission, dehydrating diarrhea, sepsis and
      hyponatremia (p<0.05 for all). Among 139 Shigella isolates, S. flexneri (88/139,
      63%) and S. sonnei(34/139, 24%) were the dominant species. S. dysenteriae was not
      isolated throughout the study period. S.sonnei was more frequently isolated from
      the cases (24/69, 35%) than the controls (10/70, 14%), whereas the isolation of
      S. flexneri was comparable between the groups (40/69, 58% vs 48/70, 69%). A total
      of 94 (67.6%) isolates were resistant to trimethoprim-sulphamethoxazole, 84
      (60.4%) to ciprofloxacin, 66/138 (48%) to ampicillin, 5 (3.5%) to ceftriaxone, 17
      (12.2%) to mecillinum and 35 (25%) to azithromycin. CONCLUSIONS/SIGNIFICANCE: The
      case-fatality-rate was significantly higher among the children with Shigella
      encephalopathy compared to those without encephalopathy. Early identification and
      aggressive management of simple risk factors for Shigella encephalopathy may help
      to reduce morbidity and deaths in such children especially in resource-limited
      settings.

PMID- 28453566
TI  - FlyLimbTracker: An active contour based approach for leg segment tracking in
      unmarked, freely behaving Drosophila.
AB  - Understanding the biological underpinnings of movement and action requires the
      development of tools for quantitative measurements of animal behavior. Drosophila
      melanogaster provides an ideal model for developing such tools: the fly has
      unparalleled genetic accessibility and depends on a relatively compact nervous
      system to generate sophisticated limbed behaviors including walking, reaching,
      grooming, courtship, and boxing. Here we describe a method that uses active
      contours to semi-automatically track body and leg segments from video image
      sequences of unmarked, freely behaving D. melanogaster. We show that this
      approach yields a more than 6-fold reduction in user intervention when compared
      with fully manual annotation and can be used to annotate videos with low spatial
      or temporal resolution for a variety of locomotor and grooming behaviors.
      FlyLimbTracker, the software implementation of this method, is open-source and
      our approach is generalizable. This opens up the possibility of tracking leg
      movements in other species by modifications of underlying active contour models.

PMID- 28453567
TI  - Performance of urine cotinine and hypomethylation of AHRR and F2RL3 as biomarkers
      for smoking exposure in a population-based cohort.
AB  - There is a growing body of evidence demonstrating an association between smoking
      and DNA methylation. Accordingly, DNA methylation is now considered a promising
      biomarker of smoking exposure. We evaluated the relationship between methylation
      markers (AHRR and F2RL3) and urine cotinine as well as self-reported smoking
      status. DNA methylation levels of AHRR and F2RL3 in blood as well as urine
      cotinine were measured in 330 adults (46 to 87 years of age). Pyrosequencing was
      performed to measure DNA methylation of AHRR and F2RL3 associated with smoking
      exposure. The lung cancer risk associated with DNA methylation and urine cotinine
      was analyzed using logistic regression analysis. The AHRR and F2RL3 genes were
      significantly hypomethylated in current smokers compared to in individuals who
      have never smoked. An inverse relationship was observed between urine cotinine
      and methylation levels. Methylation of AHRR and F2RL3 distinguished current
      smokers from never-smokers with high accuracy. Logistic multivariate analysis
      showed that AHRR methylation is significantly associated with the risk of lung
      cancer (OR = 0.96, P = 0.011). Our study validated the smoking-associated DNA
      methylation markers reported in a Korean population-based cohort. In conclusion,
      DNA methylation of AHRR and F2RL3 provided accurate measures for smoking
      exposure. Methylation markers reflecting the long-term effect of smoking on the
      risk of lung cancer showed better performance in distinguishing former smokers
      from never-smokers.

PMID- 28453568
TI  - Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled
      virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal
      implant infection model.
AB  - The quorum sensing (QS) circuit plays a role in the precise regulation of genes
      controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS
      controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has
      remained controversial due to emerging drug resistance; therefore, screening
      diverse compounds for anti-biofilm or anti-QS activities is important. This study
      demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs) of
      baicalin, an active natural compound extracted from the traditional Chinese
      medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas
      aeruginosa biofilms and enhance the bactericidal effects of various conventional
      antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory
      effects on virulence phenotypes (LasA protease, LasB elastase, pyocyanin,
      rhamnolipid, motilities and exotoxin A) regulated by QS in Pseudomonas
      aeruginosa. Moreover, the expression levels of QS-regulatory genes, including
      lasI, lasR, rhlI, rhlR, pqsR and pqsA, were repressed after sub-MIC baicalin
      treatment, resulting in significant decreases in the QS signaling molecules 3-oxo
      C12-HSL and C4-HSL, confirming the ability of baicalin-mediated QS inhibition to
      alter gene and protein expression. In vivo experiments indicated that baicalin
      treatment reduces Pseudomonas aeruginosa pathogenicity in Caenorhabditis elegans.
      Greater worm survival in the baicalin-treated group manifested as an increase in
      the LT50 from 24 to 96 h. In a mouse peritoneal implant infection model, baicalin
      treatment enhanced the clearance of Pseudomonas aeruginosa from the implants of
      mice infected with Pseudomonas aeruginosa compared with the control group.
      Moreover, the combination of baicalin and antibiotics significantly reduced the
      numbers of colony-forming units in the implants to a significantly greater degree
      than antibiotic treatment alone. Pathological and histological analyses revealed
      mitigation of the inflammatory response and reduced cell infiltration in the
      peritoneal tissue surrounding the implants after baicalin treatment. Measurement
      of the cytokine levels in the peritoneal lavage fluid of mice in the baicalin
      treatment group revealed a decrease in IL-4, an increase in interferon gamma (IFN
      gamma), and a reversed IFN-gamma/IL-4 ratio compared with the control group,
      indicating that baicalin treatment activated the Th1-induced immune response to
      expedite bacterial load clearance. Based on these results, baicalin might be a
      potent QS inhibitor and anti-biofilm agent for combating Pseudomonas aeruginosa
      biofilm-related infections.

PMID- 28453569
TI  - Molecular exploration of hidden diversity in the Indo-West Pacific sciaenid
      clade.
AB  - The family Sciaenidae, known as croakers or drums, is one of the largest
      perciform fish families. A recent multi-gene based study investigating the
      phylogeny and biogeography of global sciaenids revealed that the origin and early
      diversification of this family occurred in tropical America during the Late
      Oligocene-Early Miocene before undergoing range expansions to other seas
      including the Indo-West Pacific, where high species richness is observed. Despite
      this clarification of the overall evolutionary history of the family, knowledge
      of the taxonomy and phylogeny of sciaenid genera endemic to the Indo-West Pacific
      is still limited due to lack of a thorough survey of all taxa. In this study, we
      used DNA-based approaches to investigate the evolutionary relationships, to
      explore the species diversity, and to elucidate the taxonomic status of sciaenid
      species/genera within the Indo-West Pacific clade. Three datasets were herein
      built for the above objectives: the combined dataset (248 samples from 45
      currently recognized species) from one nuclear gene (RAG1) and one mitochondrial
      gene (COI); the dataset with only RAG1 gene sequences (245 samples from 44
      currently recognized species); and the dataset with only COI gene sequences (308
      samples from 51 currently recognized species). The latter was primarily used for
      our biodiversity exploration with two different species delimitation methods
      (Automatic Barcode Gap Discovery, ABGD and Generalized Mixed Yule Coalescent,
      GMYC). The results were further evaluated with help of four supplementary
      criteria for species delimitation (genetic similarity, monophyly inferred from
      individual gene and combined data trees, geographic distribution, and
      morphology). Our final results confirmed the validity of 32 currently recognized
      species and identified several potential new species waiting for formal
      descriptions. We also reexamined the taxonomic status of the genera,
      Larimichthys, Nibea, Protonibea and Megalonibea, and suggested a revision of
      Nibea and proposed a new genus Pseudolarimichthys.

PMID- 28453570
TI  - Contrasting effects of heat pulses on different trophic levels, an experiment
      with a herbivore-parasitoid model system.
AB  - Under predicted global climate change, species will be gradually exposed to
      warmer temperatures, and to a more variable climate including more intense and
      more frequent heatwaves. Increased climatic variability is expected to have
      different effects on species and ecosystems than gradual warming. A key challenge
      to predict the impact of climate change is to understand how temperature changes
      will affect species interactions. Herbivorous insects and their natural enemies
      belong to some of the largest groups of terrestrial animals, and thus they have a
      great impact on the functioning of ecosystems and on the services these
      ecosystems provide. Here we studied the life history traits of the plant-feeding
      insect Plutella xylostella and its specialist endoparasitoid Diadegma
      semiclausum, when exposed to a daily heat pulse of 5 or 10 degrees C temperature
      increase during their entire immature phase. Growth and developmental responses
      differed with the amplitude of the heat pulse and they were different between
      host and parasitoid, indicating different thermal sensitivity of the two trophic
      levels. With a +5 degrees C heat pulse, the adult parasitoids were larger which
      may result in a higher fitness, whereas a +10 degrees C heat pulse retarded
      parasitoid development. These results show that the parasitoid is more sensitive
      than its host to brief intervals of temperature change, and this results in
      either positive or negative effects on life history traits, depending on the
      amplitude of the heat pulse. These findings suggest that more extreme
      fluctuations may disrupt host-parasitoid synchrony, whereas moderate fluctuations
      may improve parasitoid fitness.

PMID- 28453571
TI  - Effect of Shenmai injection on preventing the development of nitroglycerin
      induced tolerance in rats.
AB  - Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing
      to increased oxidative stress and endothelial dysfunction. Shenmai injection
      (SMI), which is clinically used to treat cardiovascular diseases, consists of two
      herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have
      antioxidant effects. The present study was designed to investigate the potential
      preventive effects of Shenmai injection on development of nitroglycerin-induced
      tolerance. The present study involves both in vivo and in vitro experiments to
      investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai
      injection on the cardiovascular oxidative stress by measuring the serum levels of
      malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was
      determined by an endothelium-dependent vasorelaxation method in aortic rings and
      NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from
      released serum levels of cGMP and the protein expression levels of sGC, cGK-I,
      PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the
      decrease in AV Peak Vel, the attenuation in the vasodilation response to
      nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular
      oxidative stress by reducing the release of MDA and increasing the activity of
      SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I
      signalling pathway triggered by nitroglycerin-induced tolerance through up
      regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating
      the proteins expression of PDE1A. In vitro studies showed that Shenmai injection
      could recover the attenuated vasodilation response to nitroglycerin following
      incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC
      and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG
      nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular
      oxidative stress, meliorating the endothelial dysfunction and ameliorating the
      inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the
      potential of Shenmai injection (SMI) as a promising medicine for preventing the
      development of nitroglycerin-induced tolerance.

PMID- 28453572
TI  - Assessment of coronary artery calcium by chest CT compared with EKG-gated cardiac
      CT in the multicenter AIDS cohort study.
AB  - RATIONALE: Individuals with HIV are at increased risk for coronary artery disease
      (CAD). Early detection of subclinical CAD by assessment of coronary artery
      calcium (CAC) may help risk stratify and prevent CAD events in these individuals.
      However, the current standard to quantify CAC i.e. Agatston scoring requires EKG
      gated cardiac CT imaging. OBJECTIVE: To determine if the assessment of CAC using
      non-EKG-gated chest CT and the Weston scoring system is a useful surrogate for
      Agatston scores in HIV-infected and HIV-uninfected individuals. METHODS AND
      MEASUREMENTS: CAC was assessed by both the Weston and Agatston score in 108 men
      enrolled in the Multicenter AIDS Cohort Study. RESULTS: Participants were 55.2
      (IQR 50.4; 59.9) years old and 62 (57.4%) were seropositive for HIV. Inter
      observer agreement (rs = 0.94, kappa = 90.0%, p<0.001, n = 21) and intra-observer
      agreement (rs = 0.95, kappa = 95.2%, p<0.001, n = 97) for category of Weston
      score were excellent. Weston scores were associated with similar CAD risk factors
      as Agatston scores (age, race, HDL cholesterol level, all p<0.05) in our cohort.
      There was excellent correlation (rs = 0.92, p<0.001) and agreement (kappaw =
      0.77, p<0.001) between Weston and Agatston scores. CONCLUSIONS: This study is the
      first to examine calcium scoring using chest CT in HIV-infected individuals and
      to independently validate the Weston score as a surrogate for the Agatston score.
      In clinical or research settings where EKG-gated cardiac CT is not feasible for
      the assessment of coronary calcium, Weston scoring by using chest CT should be
      considered.

PMID- 28453573
TI  - How reliable and valid is the teacher version of the Strengths and Difficulties
      Questionnaire in primary school children?
AB  - INTRODUCTION: The Strengths and Difficulties Questionnaire (SDQ) is validated for
      parents, but not yet for teachers in a broad age range of children. We conducted
      a cross-sectional study with 4-10 years old school children to investigate if the
      SDQ-T can be used instead of the validated but lengthy Teacher's Report Form
      (TRF) to acquire information about emotional and behavioral problems in the
      school community. METHODS: Teachers of 453 children from primary schools were
      approached. Teachers of 394 children (response rate 86.9%) with a mean age of 7.1
      years filled in the SDQ-T (n = 387), the TRF (n = 349) or both (n = 342). We
      assessed reliability by calculating internal consistency and concurrent validity
      (using correlation coefficients, sensitivity, specificity) of the SDQ-T compared
      with the TRF. RESULTS: Internal consistency of the SDQ-T Total Difficulties Score
      (SDQ-T TDS; Cronbach alpha = 0.80), hyperactivity/ inattention- (alpha = 0.86)
      and prosocial behavior (alpha = 0.81) was very good. Concurrent validity
      demonstrated a strong correlation of all subscales of the SDQ-T with the
      corresponding scale on the TRF (range 0.54-0.73), except for peer problems
      (0.46). Using a SDQ-T TDS cut-off score > 14, the SDQ-T had a good sensitivity
      (90%) and specificity (94%). DISCUSSION: The good reliability, validity and
      brevity of the SDQ-T make it an easily applicable questionnaire for obtaining
      information about emotional and behavioral problems from teachers in primary
      school children.

PMID- 28453574
TI  - Social defeat stress causes depression-like behavior with metabolite changes in
      the prefrontal cortex of rats.
AB  - Major depressive disorder is a serious mental disorder with high morbidity and
      mortality. The role of social stress in the development of depression remains
      unclear. Here, we used the social defeat stress paradigm to induce depression
      like behavior in rats, then evaluated the behavior of the rats and measured
      metabolic changes in the prefrontal cortex using gas chromatography-mass
      spectrometry. Within the first week after the social defeat procedure, the
      sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM)
      and forced swim test (FST) were conducted to examine the depressive-like and
      anxiety-like behaviors. For our metabolite analysis, multivariate statistics were
      applied to observe the distribution of all samples and to differentiate the
      socially defeated group from the control group. Ingenuity pathway analysis was
      used to find the potential relationships among the differential metabolites. In
      the OFT and EPM, there were no significant differences between the two
      experimental groups. In the SPT and FST, socially defeated rats showed less
      sucrose intake and longer immobility time compared with control rats. Metabolic
      profiling identified 25 significant variables with good predictability. Ingenuity
      pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid
      Metabolism" was the most significantly altered network. Stress-induced
      alterations of low molecular weight metabolites were observed in the prefrontal
      cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy
      metabolism were significantly perturbed. The results of this study suggest that
      repeated social defeat can lead to metabolic changes and depression-like behavior
      in rats.

PMID- 28453576
TI  - A novel framework for the identification of drug target proteins: Combining
      stacked auto-encoders with a biased support vector machine.
AB  - The identification of drug target proteins (IDTP) plays a critical role in
      biometrics. The aim of this study was to retrieve potential drug target proteins
      (DTPs) from a collected protein dataset, which represents an overwhelming task of
      great significance. Previously reported methodologies for this task generally
      employ protein-protein interactive networks but neglect informative biochemical
      attributes. We formulated a novel framework utilizing biochemical attributes to
      address this problem. In the framework, a biased support vector machine (BSVM)
      was combined with the deep embedded representation extracted using a deep
      learning model, stacked auto-encoders (SAEs). In cases of non-drug target
      proteins (NDTPs) contaminated by DTPs, the framework is beneficial due to the
      efficient representation of the SAE and relief of the imbalance effect by the
      BSVM. The experimental results demonstrated the effectiveness of our framework,
      and the generalization capability was confirmed via comparisons to other models.
      This study is the first to exploit a deep learning model for IDTP. In summary,
      nearly 23% of the NDTPs were predicted as likely DTPs, which are awaiting further
      verification based on biomedical experiments.

PMID- 28453575
TI  - Genome-wide association study of red blood cell traits in Hispanics/Latinos: The
      Hispanic Community Health Study/Study of Latinos.
AB  - Prior GWAS have identified loci associated with red blood cell (RBC) traits in
      populations of European, African, and Asian ancestry. These studies have not
      included individuals with an Amerindian ancestral background, such as
      Hispanics/Latinos, nor evaluated the full spectrum of genomic variation beyond
      single nucleotide variants. Using a custom genotyping array enriched for
      Amerindian ancestral content and 1000 Genomes imputation, we performed GWAS in
      12,502 participants of Hispanic Community Health Study and Study of Latinos
      (HCHS/SOL) for hematocrit, hemoglobin, RBC count, RBC distribution width (RDW),
      and RBC indices. Approximately 60% of previously reported RBC trait loci
      generalized to HCHS/SOL Hispanics/Latinos, including African ancestral alpha- and
      beta-globin gene variants. In addition to the known 3.8kb alpha-globin copy
      number variant, we identified an Amerindian ancestral association in an alpha
      globin regulatory region on chromosome 16p13.3 for mean corpuscular volume and
      mean corpuscular hemoglobin. We also discovered and replicated three genome-wide
      significant variants in previously unreported loci for RDW (SLC12A2 rs17764730,
      PSMB5 rs941718), and hematocrit (PROX1 rs3754140). Among the proxy variants at
      the SLC12A2 locus we identified rs3812049, located in a bi-directional promoter
      between SLC12A2 (which encodes a red cell membrane ion-transport protein) and an
      upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant.
      We further demonstrate that disruption of the regulatory element harboring
      rs3812049 affects transcription of SLC12A2 and LINC01184 in human erythroid
      progenitor cells. Together, these results reinforce the importance of genetic
      study of diverse ancestral populations, in particular Hispanics/Latinos.

PMID- 28453577
TI  - Abdominal aortic aneurysm screening program using hand-held ultrasound in primary
      healthcare.
AB  - We determined the feasibility of abdominal aortic aneurysm (AAA) screening
      program led by family physicians in public primary healthcare setting using hand
      held ultrasound device. The potential study population was 11,214 men aged >= 60
      years attended by three urban, public primary healthcare centers. Participants
      were recruited by randomly-selected telephone calls. Ultrasound examinations were
      performed by four trained family physicians with a hand-held ultrasound device
      (Vscan(r)). AAA observed were verified by confirmatory imaging using standard
      ultrasound or computed tomography. Cardiovascular risk factors were determined.
      The prevalence of AAA was computed as the sum of previously-known aneurysms,
      aneurysms detected by the screening program and model-based estimated undiagnosed
      aneurysms. We screened 1,010 men, with mean age of 71.3 (SD 6.9) years; 995
      (98.5%) men had normal aortas and 15 (1.5%) had AAA on Vscan(r). Eleven out of 14
      AAA-cases (78.6%) had AAA on confirmatory imaging (one patient died). The total
      prevalence of AAA was 2.49% (95%CI 2.20 to 2.78). The median aortic diameter at
      diagnosis was 3.5 cm in screened patients and 4.7 cm (p<0.001) in patients in
      whom AAA was diagnosed incidentally. Multivariate logistic regression analysis
      identified coronary heart disease (OR = 4.6, 95%CI 1.3 to 15.9) as the
      independent factor with the highest odds ratio. A screening program led by
      trained family physicians using hand-held ultrasound was a feasible, safe and
      reliable tool for the early detection of AAA.

PMID- 28453578
TI  - Effects of a mixture of chloromethylisothiazolinone and methylisothiazolinone on
      peripheral airway dysfunction in children.
AB  - BACKGROUND: Children who were only exposed to a mixture of
      chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) as humidifier
      disinfectant (HD) components were evaluated for humidifier disinfectant
      associated lung injury (HDLI) from 2012. This study was to evaluate the pulmonary
      function using, impulse oscillometry (IOS) for children exposed to a mixture of
      CMIT/MIT from HD. METHODS: Twenty-four children who were only exposed to a
      mixture of CMIT/MIT, with no previous underlying disease, were assessed by IOS.
      Diagnostic criteria for HDLI were categorized as definite, probable, possible, or
      unlikely. Home visits and administration of a standardized questionnaire were
      arranged to assess exposure characteristics. RESULTS: Definite and probable cases
      showed higher airborne disinfectant exposure intensity during sleep (32.4 +/- 8.7
      MUg/m3) and younger age at initial exposure (3.5 +/- 3.3 months) compared with
      unlikely cases (17.3 +/- 11.0 MUg/m3, p = 0.026; 22.5 +/- 26.2 months, p = 0.039,
      respectively). Reactance at 5 Hz was significantly more negative in those with
      high-density exposure during sleep (mean, -0.463 kPa/L/s vs. low density, -0.296,
      p = 0.001). The reactance area was also higher with high-density exposure during
      sleep (mean, 3.240 kPa/L vs. low density, 1.922, p = 0.039). The mean
      bronchodilator response with high-density exposure was within the normal range
      for reactance. CONCLUSIONS: Significant peripheral airway dysfunction were found
      in children with high levels of inhalation exposure to a mixture of CMIT/MIT
      during sleep. Strict regulation of a mixture of CMIT/MIT exposure were associated
      with positive effects on lung function of children.

PMID- 28453579
TI  - Studies on bacterial community composition are affected by the time and storage
      method of the rumen content.
AB  - The objective of this study was to investigate three storage methods and four
      storage times for rumen sampling in terms of quality and yield of extracted
      metagenomic DNA as well as the composition of the rumen bacterial community. One
      Nellore steer fitted with a ruminal silicone-type cannula was used as a donor of
      ruminal contents. The experiment comprised 11 experimental groups: pellet control
      (PC), lyophilized control (LC), P-20: pellet stored frozen at -20 degrees C for a
      period of 3, 6, and 12 months, P-80: pellet stored frozen at -80 degrees C for a
      period of 3, 6, and 12 months, and L-20: lyophilized sample stored frozen at -20
      degrees C for a period of 3, 6, and 12 months. Metagenomic DNA concentrations
      were measured spectrophotometrically and fluorometrically and ion torrent
      sequencing was used to assess the bacterial community composition. The L-20
      method could not maintain the yield of DNA during storage. In addition, the P-80
      group showed a greater yield of metagenomic DNA than the other groups after 6
      months of storage. Rumen samples stored as pellets (P-20 and P-80) resulted in
      lower richness Chao 1, ACE, and Shannon Wiener indices when compared to PC, while
      LC and PC were only different in richness ACE. The storage method and storage
      time influenced the proportions of 14 of 17 phyla identified by sequencing. In
      the P-20 group, the proportion of Cyanobacteria, Elusimicrobia, Fibrobacteres,
      Lentisphaerae, Proteobacteria, and Spirochaetes phyla identified was lower than
      1%. In the P-80 group, there was an increase in the proportion of the
      Bacteroidetes phylum (p = 0.010); however, the proportion of Actinobacteria,
      Chloroflexi, SR1, Synergistetes, TM7, and WPS.2 phyla were unchanged compared to
      the PC group (p > 0.05). The class Clostridium was the most abundant in all
      stored groups and increased in its proportion, especially in the L-20 group. The
      rumen sample storage time significantly reduced the yield of metagenomic DNA
      extracted. Therefore, the storage method can influence the abundance of phyla,
      classes, and bacterial families studied in rumen samples and affect the richness
      and diversity index.

PMID- 28453580
TI  - [Health-related quality of life in Chilean patients with chronic obstructive
      pulmonary disease].
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has a relevant impact on
      health-related quality of life (HRQoL). Short Form 6 dimensions (SF-6D) quality
      of life tool allows researchers to calculate preference-based utilities using
      data from SF-12 or SF-36 questionnaires. AIM: To provide normative values of SF
      6D derived from SF-12 for Chilean patients with COPD. MATERIAL AND METHODS: SF-6D
      utility index was calculated using data from the 2009/2010 Chilean National
      Health Survey. Sixty-nine male and 120 female patients with COPD participated in
      the survey. Data was stratified by gender, age, region, marital status, smoking
      status, monthly incomes, educational level and area. RESULTS: The mean (+/- SD)
      SF-6D utility index for Chilean patients with COPD was 0.65 +/- 0.15. The scores
      for men and women were 0.68 +/- 0.15 and 0.64 +/- 0.15, respectively. Patients
      with high incomes and educational level reported higher SF-6D scores. Ceiling
      effect was not a limitation when SF-6D was used in these Chilean patients.
      CONCLUSIONS: The current study provides normative values of SF-6D derived from SF
      12 for Chilean patients with COPD.

PMID- 28453581
TI  - [A score to predict medical emergencies in hospitalized patients].
AB  - BACKGROUND: The medical alert system (MAS) was created for the timely handling of
      clinical decompensations, experienced by patients hospitalized at the Medical
      Surgical Service (MSS) in a private clinic. It is activated by the nurse when
      hemodynamic, respiratory, neurological, infectious or metabolic alterations
      appear, when a patient falls or complains of pain. A physician assesses the
      patient and decides further therapy. AIM: To analyze the clinical and demographic
      characteristics of patients who activated or not the MAS and develop a score to
      identify patients who will potentially activate MAS. MATERIAL AND METHODS: Data
      from 13,933 patients discharged from the clinic in a period of one year was
      analyzed. RESULTS: MAS was activated by 472 patients (3.4%). Twenty two of these
      patients died during hospital stay compared to 68 patients who did not activate
      the alert (0.5%, p < 0.01). The predictive score developed considered age,
      diagnosis (based on the tenth international classification of diseases) and
      whether the patient was medical or surgical. The score ranges from 0 to 9 and a
      cutoff >= 6 provides a sensitivity and specificity of 37 and 81% respectively and
      a positive likelihood ratio (LR+) of 1.9 to predict the activation of MAS. The
      same cutoff value predicts death with a sensitivity and specificity of 80% and a
      negative predictive value of 99.8%. CONCLUSIONS: This score may be useful to
      identify hospitalized patients who may have complications during their hospital
      stay.

PMID- 28453582
TI  - [Frailty in patients admitted to hospital with acute decompensated heart
      failure].
AB  - BACKGROUND: Frailty is a geriatric syndrome characterized by a progressive
      impairment in the subjects? ability to respond to environmental stress. Frailty
      is more commonly found in heart failure (HF) patients than in general population
      and it is an independent predictor of rehospitalization, emergency room visits
      and death. AIM: To estimate the prevalence of frailty in patients with
      decompensated HF admitted to four hospitals in Santiago, Chile. MATERIAL AND
      METHODS: Cross-sectional study. Subjects aged 60 or older consecutively admitted
      for decompensated HF to the study centers between August 2014 and March 2015 were
      included. Frailty was defined as the presence of three or more of the following
      criteria: unintended weight loss, muscular weakness, depression symptoms
      (exhaustion), reduced gait speed and low physical activity. Independent variables
      were tested for association using simple logistic regression. Variables
      associated with frailty (p < 0.05) were included in a multiple logistic
      regression model. RESULTS: Seventy-nine subjects were included. The prevalence of
      frailty was 50.6%. Frail patients were mostly female (52.6%) and older than non
      frail subjects (73.7+/- 7.9 vs 68.2 +/- 7.1; p < 0.003). Independent predictors
      of frailty were age (Odds raio (OR) 1.10; 95% confidence intervals (CI): 1.03
      1.17), quality of life measured with the Minnesota Living with Heart Failure
      Questionnaire (OR 1.07; IC95%: 1.03-1.11), previous hospitalizations (OR 2.56;
      95%CI: 1.02-6.43) and number of medications (OR 4.46; 95%CI: 1.11-17.32).
      CONCLUSIONS: The prevalence of frailty in patients admitted to the hospital for
      decompensated heart failure is high. Age, quality of life, hospitalizations and
      polypharmacy were factors associated with frailty in this group of participants.

PMID- 28453583
TI  - [Validation of the successful aging inventory in chilean older people].
AB  - BACKGROUND: There is a paucity of adequate and validated instruments for the
      measurement of successful aging for geriatric researchers in Chile. AIM: To
      validate the ?Successful Aging Inventory? (SAI) in Chilean older people. MATERIAL
      AND METHODS: SAI was answered by 777 older people aged 70 +/- 7 years (63% women)
      living in urban and rural areas, including the highlands of a Northern desert
      region of Chile. RESULTS: A Cronbach alfa of 0.92 was obtained for the general
      dimension of successful aging. The figures for each dimension included in the
      theoretical model (functional performance, intrapsychic factors, gero
      transcendence; spirituality; purpose and life satisfaction), and ranged from 0.66
      to 0.91. Confirmatory factorial analysis showed that the original inventory
      model, fits with the data collected from Chilean people. CONCLUSIONS: Successful
      Aging Inventory (SAI) is a reliable and adequate inventory, which can be used in
      Chilean older people.

PMID- 28453584
TI  - [Effectiveness of a structured educative program in Chilean diabetic patients].
AB  - BACKGROUND: Structured educative programs have demonstrated their usefulness as a
      strategy to improve metabolic control in diabetic patients. AIM: To evaluate the
      effectiveness of a structured educative program for Chilean diabetic patients.
      MATERIAL AND METHODS: A randomized clinical trial in diabetic patients with
      glycosylated hemoglobin over 7.5%. One hundred fifteen patients were studied, 59
      patients participated in the structured educative program (experimental group)
      and 56 patients received no structured education (control group). Patients were
      followed for 12 months. RESULTS: Between baseline and 12 months of follow-up,
      glycosylated hemoglobin changed from 10.05 to 9.11% in experimental patients and
      from 9.86 to 9.25% in controls. No significant differences between experimental
      and control groups in other clinical and metabolic parameters were observed. In
      the experimental group, glycosylated hemoglobin reductions differed among the
      different educators who carried out the program. CONCLUSIONS: A structured
      educative program resulted in a 35% greater reduction in glycosylated hemoglobin
      levels, compared with a control group. Metabolic control improvement differed
      between the educators who carried out the program.

PMID- 28453585
TI  - [Usefulness of the activities of daily living questionnaire (T-ADLQ) in patients
      with minor stroke].
AB  - BACKGROUND: The inability to carry out activities of daily living (ADL) is
      prevalent in elderly people and it is associated with hypertension and stroke.
      AIM: To evaluate ADLs using the T-ADLQ in hypertensive patients with minor
      stroke. SUBJECTS AND METHODS: T-ADLQ, Cognitive tests (Minimental and
      Addenbrooke), and Hamilton depression test were applied to 100 hypertensive
      ambulatory patients (55 without symptomatic stroke and 45 with ischemic stroke,
      Rankin <= 2). RESULTS: In stroke patients the ability to perform ADL was
      significantly reduced compared with hypertensive patients without stroke.
      Cognitive dysfunction and depressive symptoms were associated with a lower ADL
      performance. CONCLUSIONS: The T-ADLQ is useful to evaluate ADL in hypertensive
      ambulatory patients with ischemic stroke.

PMID- 28453586
TI  - [Incidence of aphasia in patients experiencing an ischemic stroke].
AB  - BACKGROUND: Sequelae after a stroke are common and may lead to disability.
      Aphasia - defined as an acquired language disturbance - can cause important
      limitations in quality of life. AIM: To describe the epidemiological features of
      patients who had an aphasia after a first episode of ischemic stroke and their
      functional outcome at six months. MATERIAL AND METHODS: Review of a database of a
      population study on the incidence, 30-day case fatality rate, and prognosis of
      stroke performed in a northern Chilean city between 2000 and 2002. RESULTS:
      Aphasia was diagnosed in 28 of 142 patients in whom the disorder was sought
      (20%). The projected incidence rate in the city where the study was carried out
      is 7.06 per 100,000 inhabitants. The mean age of these 28 patients was 66 +/- 20
      years and 53% were women. The main risk factor for stroke was hypertension in
      62%. The etiology of stroke was undetermined in 64% of these patients. Partial
      anterior circulation infarction was the most common stroke location in 61%.
      CONCLUSIONS: Twenty percent of patients with a first episode of ischemic stroke
      have aphasia.

PMID- 28453587
TI  - [Association of physical activity and dietary habits with overweight in fertile
      Chilean women].
AB  - BACKGROUND: Women in Chile are mainly responsible in the formation of eating
      habits in the population, particularly at their homes. AIM: To explore the
      association of physical activity and alimentary habits with overweight among
      adult Chilean women in fertile age. MATERIAL AND METHODS: Cross sectional study
      using the data from de National Health Survey 2009-2010. Socio-demographic
      variables, dietary issues, multidimensional physical activity, sedentary free
      time and their link with nutritional status were studied in a sample of 1,195
      women aged between 20 and 44 years. RESULTS: Sixty three percent of women were
      overweight. The factors positively associated overweight were having an age
      between 31 and 44 years (prevalence ratio (PR) = 1.4), having a lower education
      level (PR = 1.23), living in rural areas (PR = 2.21) and being exposed to work
      environment (PR = 1.29). The factors negatively associated with overweight were
      the consumption of whole grains at least once daily (PR = 0.59), being physically
      active according to a self-assessment scale (PR = 0.22) and being physically
      inactive during leisure time (PR = 0.61). CONCLUSIONS: The promotion whole grain
      cereal consumption and physical activity in women is advisable to prevent
      overweight, mostly in vulnerable groups such as those older than 31 years, with a
      low educational level and living rural areas.

PMID- 28453588
TI  - [Diverticular disease: myths and realities].
AB  - Diverticulosis and diverticular disease of the colon are common conditions in
      Western countries. The incidence and prevalence of these diseases are increasing
      and becoming significant for health systems. A growing body of knowledge is
      shifting the paradigm of the pathogenesis and treatment of diverticular disease.
      Low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity,
      and abnormal colonic motility have been identified as factors leading to
      diverticular disease. The risk of developing diverticulitis among individuals
      with diverticulosis is lower than 10 to 25%. Studies indicate that diverticular
      disease may become a chronic disorder in some patients, not merely an acute
      illness. Contrary to the advice from international guidelines, studies have not
      shown that a high-fiber diet protects against diverticulosis. The evidence about
      the use of antibiotics in uncomplicated diverticulitis is sparse and of low
      quality. In relation to surgery, studies support a more conservative approach to
      prophylactic surgery in patients with recurrent disease or chronic symptoms.
      Finally, new pathophysiological knowledge suggests that other treatments may be
      useful (mesalamine, rifaximin and probiotics). However, more research is
      necessary to validate the safety, effectiveness and cost-effectiveness of these
      strategies.

PMID- 28453589
TI  - [Effects of prebiotics and probiotics on gastrointestinal tract lymphoid tissue
      in hiv infected patients].
AB  - HIV infection induces alterations in almost all immune cell populations, mainly
      in CD4+ T cells, leading to the development of opportunistic infections. The gut
      associated lymphoid tissue (GALT) constitutes the most important site for viral
      replication, because the main target cells, memory T-cells, reside in this
      tissue. It is currently known that alterations in GALT are critical during the
      course of the infection, as HIV-1 induces loss of tissue integrity and promotes
      translocation of microbial products from the intestinal lumen to the systemic
      circulation, leading to a persistent immune activation state and immune
      exhaustion. Although antiretroviral treatment decreases viral load and
      substantially improves the prognosis of the infection, the alterations in GALT
      remains, having a great impact on the ability to establish effective immune
      responses. This emphasizes the importance of developing new therapeutic
      alternatives that may promote structural and functional integrity of this tissue.
      In this regard, therapy with probiotics/prebiotics has beneficial effects in
      GALT, mainly in syndromes characterized by intestinal dysbiosis, including the
      HIV-1 infection. In these patients, the consumption of probiotics/prebiotics
      decreased microbial products in plasma and CD4+ T cell activation, increased CD4+
      T cell frequency, in particular Th17, and improved the intestinal flora. In this
      review, the most important findings on the potential impact of the
      probiotics/prebiotics therapy are discussed.

PMID- 28453590
TI  - [Understanding cortisol action in acute inflammation: A view from the adrenal
      gland to the target cell].
AB  - Glucocorticoids (cortisol in humans) are essential for numerous biological
      functions. Among critically ill patients, therapy with cortisol has gained
      strength in recent years, but clinical results have been mixed. A series of
      events, that may explain the diversity of clinical responses, occur from the
      synthesis of cortisol in the adrenal gland to the activation of the cortisol
      receptor by the hormone when it enters the nucleus of the target cell. Some of
      these events are revised; a proposition for identifying critically ill patients
      who may benefit with this therapy is suggested.

PMID- 28453591
TI  - [The impact of tap water fluoridation on human health].
AB  - The purpose of this review is to describe the osteological, neurological,
      endocrine and dermatological effects of fluoride ingestion. Additional aims are
      to evaluate whether the Chilean tap water fluoridation program has had any impact
      on dental health, and analyze the basis for the Chilean elementary school milk
      fluoridation program, which is targeted at children living in places where tap
      water has a fluoride concentration less than 0.3 mg/L, without any artificial
      fluoridation process. We discuss the finding that both public measures have no
      direct or remarkable effect on dental health, since topical dental hygiene
      products are the main and most effective contributors to the prevention of dental
      decay. We also suggest that the permanent and systematic ingestion of fluorides
      imposes health risks on the population. Therefore, we recommend reevaluating the
      national fluoridation program for public tap water and the elementary school milk
      program.

PMID- 28453592
TI  - [Cutaneous myiasis due to Cochliomyia hominivorax associated with seborrheic
      dermatitis].
AB  - Myiasis is an infestation of tissues and organs of humans and animals by Diptera
      larvae (flies, horseflies, mosquitoes). They are located at different body sites,
      and classified clinically as cutaneous, visceral and cavitary. We report a 26
      year-old woman with a history of seborrheic dermatitis and recent trip to Brazil.
      She presented with a seven days history of suppurating wounds in the parieto
      occipital area of the scalp. At physical examination we found three ulcers of
      approximately 1.5 cm each, with multiple mobile larvae inside. The obtained
      larvae were analyzed, identifying Cochliomyia hominivorax larvae at L2 and L3
      stages. The patient was managed successfully with oral antimicrobials and local
      cleansing. The screwworm Cochliomyia hominivorax in our country is rare. Known
      risk factors are wounds, poor personal hygiene, extreme ages, psychiatric
      disorders, presence of specific dermatosis such as psoriasis and seborrheic
      dermatitis, among others.

PMID- 28453593
TI  - [Benign intraperitoneal metastatic leiomyomatosis: A case report].
AB  - Benign intraperitoneal metastatic leiomyomatosis is a rare benign disease that is
      observed when a leiomyoma is present in the peritoneal surface. Women who have
      undergone hysterectomy for leiomyomas are most commonly affected. Patients are
      usually asymptomatic at presentation, being frequently an incidental finding in
      imaging studies. Ultrasound and CT play an important role in the diagnosis. The
      lesions are histologically identical to their uterine counterparts. There are
      different theories about the pathogenesis of the disease, including peritoneal
      seeding after laparoscopic hysterectomy. Others support the hypothesis of
      multiple independent foci of smooth muscle proliferation. Treatment, as in
      uterine leiomyomatosis, is generally conservative. We report a 53-year-old
      hysterectomized woman with intraperitoneal leiomyomas detected in a routine
      physical examination as mobile abdominal masses who underwent successful
      laparoscopic resection.

PMID- 28453594
TI  - [Shock as an adverse reaction to rituximab: Case report].
AB  - Rituximab is a plausible alternative first-line treatment of ANCA-associated
      vasculitis. Adverse effects related to its infusion are common and usually have a
      benign course. However, there have been reports of refractory cardiogenic shock
      simulating septic shock. We report an 81-year-old male with the diagnosis of ANCA
      associated vasculitis. Rituximab 500 mg was administered intravenously for a
      relapse. The infusion proceeded without incident. However, 24 hours after its
      administration the patient began with fever, chills, coughing and strong malaise.
      The patient was transferred to the critical patient unit where a septic shock was
      suspected and resuscitative measures were started. However, the fast response to
      moderate doses of vasoactive drugs and complementary tests did not support an
      infectious etiology for the shock. Antimicrobials were discontinued and systemic
      corticosteroids were maintained, achieving remission of the symptoms. Shock as an
      unusual adverse reaction to Rituximab was suspected.

PMID- 28453595
TI  - [Eyelid retraction of neurologic origin: Report of three cases].
AB  - Eyelid retraction, has received limited attention and it has passively been
      interpreted as the result of an overactive levator palpebrae superioris muscle
      secondary to midbrain injury. However, eyelid retractions can occur in other
      neurological diseases, not directly related with the midbrain. We report three
      patients who developed eyelid retraction. One patient had a bilateral eyelid
      retraction, related with Creutzfeldt-Jakob disease (CJD). Another patient had a
      unilateral right eyelid retraction associated with a thalamic-mesencephalic
      infarct. The third patient had a bilateral pontine infarction on magnetic
      resonance imaging. In the patient with CJD, eyelid retraction did not subside.
      Among patients with infarctions, the retraction persisted after focal symptoms
      had subsided, showing an evolution that was apparently independent of the basic
      process. The analysis of these patients allows us to conclude that the
      pathogenesis of eyelid retraction includes supranuclear mechanisms in both the
      development and maintenance of the phenomenon. Unilateral or bilateral eyelid
      retraction does not alter the normal function of eyelid, which ever had normal
      close eye blink. In these reported cases, a hyperactivity of levator palpebrae
      superioris muscle was clinically ruled out.

PMID- 28453596
TI  - [It is time to focus on unpaid caregiving].

PMID- 28453597
TI  - [A modification of Cronbach?s alpha coefficient by correlated errors].

PMID- 28453598
TI  - [Reliability calculation using the McDonald?s Omega coefficient].

PMID- 28453599
TI  - [Ethical Challenges in Nephrological Clinic].

PMID- 28453600
TI  - Whole Exome Sequencing in Eight Thai Patients With Leber Congenital Amaurosis
      Reveals Mutations in the CTNNA1 and CYP4V2 Genes.
AB  - Purpose: Our goal was to describe the clinical and molecular genetic findings in
      Thai patients with Leber congenital amaurosis (LCA). Methods: Whole exome
      sequencing (WES) was performed in eight unrelated patients. All genes responsible
      for inherited retinal diseases (IRDs) based on RetNet were selected for analysis.
      Potentially causative variants were filtered through a bioinformatics pipeline
      and validated using Sanger sequencing. Segregation analysis of the causative
      genes was performed in family members when available. Results: Eleven deleterious
      variants, six nonsense and five missense, were identified in seven genes: four
      LCA-associated genes (CEP290, IQCB1, NMNAT1, and RPGRIP1), one gene responsible
      for syndromic LCA (ALMS1), and two IRDs-related genes (CTNNA1 and CYP4V2).
      Clinical reassessment supported the diagnosis of syndromic LCA in those patients
      harboring potentially pathogenic variants in the ALMS1. Interestingly, two
      causative genes, CTNNA1 and CYP4V2, previously reported to cause butterfly-shaped
      pigment dystrophy (BSPD) and Bietti's crystalline dystrophy (BCD), respectively,
      were detected in two other patients. These two patients developed rapid and
      severe visual loss in contrast to BSPD and BCD patients in previous studies. The
      results of this study demonstrate that causative variants identified in the
      CTNNA1 and CYP4V2 genes are also associated with LCA. Conclusions: This is the
      first report describing the molecular genetics and clinical manifestations of
      Thai patients with LCA. The present study expands the spectrum of LCA-associated
      genes, which is a benefit for molecular diagnosis. The identification of
      mutations in the CTNNA1 and CYP4V2 genes requires further elucidation in larger
      cohorts with LCA.

PMID- 28453601
TI  - Time Spent Commuting to Work and Mental Health: Evidence From 13 Waves of an
      Australian Cohort Study.
AB  - Time-related stressors, such as long working hours, are recognized as being
      detrimental to health. We considered whether time spent commuting to work was a
      risk factor for poor mental health. Data from the Household, Income Labour
      Dynamics in Australia Survey were used to conduct fixed-effects longitudinal
      regression analyses. The outcome variable was the Mental Health Inventory, and
      the main exposure represented hours per week traveling to and from a place of
      paid employment. Effect modifiers included sex, low job control, high demands,
      and low job security. Compared with when a person commuted for <=2 hours per
      week, there was a small decline (coefficient = -0.33, 95% CI: -0.62, -0.04; P =
      0.025) in the Mental Health Inventory score when they commuted for over 6 hours
      per week. Compared with persons with high job control, persons working in jobs
      with low job control experienced significantly greater declines in the Mental
      Health Inventory score when commuting 4 to 6 hours per week and when commuting
      over 6 hours per week. We found no influence from the other hypothesized effect
      modifiers. These results suggest the importance of considering commuting time as
      an additional work-related time stressor.

PMID- 28453602
TI  - Theory of Mind and Executive Functioning Following Stroke.
AB  - Objective: Cognitive deficits following stroke are well documented, but less is
      known about problems with social skills such as understanding others' thoughts
      and feelings. This study investigated the effect of stroke on a visual-affective
      measure of social understanding: the Reading the Mind in the Eyes test (RMET).
      The aims were to investigate whether right hemisphere stroke was particularly
      detrimental to this aspect of Theory of Mind (ToM), and investigate the
      relationship between ToM ability and executive function following stroke.
      Methods: Performance of stroke patients (right hemisphere stroke, n = 15; left
      hemisphere stroke, n = 15) was compared to that of controls (n = 40) matched for
      age, years of education, and IQ on tasks measuring ToM and executive functioning.
      Results: Right hemisphere stroke was associated with impaired ToM ability, but
      left hemisphere stroke was not. There was no effect of stroke on a matched non
      ToM control task. High correlations were found between performance on the RMET
      and some measures of executive functioning in participants with right hemisphere
      stroke only. Further analyses suggested that deficits in executive functioning
      could not statistically explain all of the difficulties shown by stroke
      participants on the RMET. Conclusions: A reduction in the ability to attribute
      mental states to others following right hemisphere stroke may adversely affect
      psychosocial functioning, disrupt interpersonal relationships, and lead to
      reduced quality of life. The clinical importance of these findings, implications
      for clinical practice and future research are discussed.

PMID- 28453603
TI  - The Effect of Insomnia on Neuropsychological Functioning in Patients with
      Comorbid Symptoms of Pain, Fatigue, and Mood Disorders.
AB  - Objectives: To examine if elevated symptoms of insomnia affects
      neuropsychological functioning in patients with concurrent symptoms of pain,
      fatigue, and mood disorders. Methods and results: A total of seventy-six subjects
      participated in this (cross-sectional) study. Based on the cut-off score
      guidelines from The Insomnia Severity Index subjects were assigned to either a
      clinical insomnia group (N = 35) or a comparison group (N = 41). Factors such as
      age, general cognitive functioning, and symptoms of pain, fatigue, depression,
      and anxiety did not differ between the groups. Both groups completed a
      questionnaire which assessed subjective memory functioning. In addition they
      completed a set of neuropsychological tests measuring general cognitive
      functioning, spatial and verbal working memory, and inhibitory control. Although
      the subjects with clinical insomnia did not report more memory problems than the
      comparison group, they presented significant deficiencies on the tests assessing
      spatial and verbal working memory. There was no difference between the groups in
      inhibitory control. Conclusions: This study shows that as the symptom severity of
      insomnia increases and become clinically significant, it has substantial effect
      on both spatial and verbal-numeric working memory functioning. By differentiating
      and testing different domains of working memory, this study provides a more
      detailed and nuanced characterization of working memory deficiencies than the
      previous studies within this field. The results need to be transferred to
      clinical practice so that neuropsychologists include assessments of sleep as part
      of their routine screenings.

PMID- 28453604
TI  - Modeling Seasonal and Spatiotemporal Variation: The Example of Respiratory
      Prescribing.
AB  - Many measures of chronic diseases, including respiratory disease, exhibit
      seasonal variation together with residual correlation between consecutive time
      periods and neighboring areas. We demonstrate a strategy for modeling data that
      exhibit both seasonal trend and spatiotemporal correlation, using an application
      to respiratory prescribing. We analyzed 55 months (2002-2006) of prescribing data
      from the northeast of England, in the United Kingdom. We estimated the seasonal
      pattern of prescribing by fitting a dynamic harmonic regression (DHR) model to
      salbutamol prescribing in relation to temperature. We compared the output of DHR
      models to static sinusoidal regression models. We used the DHR-fitted values as
      an offset in mixed-effects models that aimed to account for the remaining
      spatiotemporal variation in prescribing rates. As diagnostic checks, we assessed
      spatial and temporal correlation separately and jointly. Our application of a DHR
      model resulted in a better fit to the seasonal variation of prescribing than was
      obtained with a static model. After adjusting for the fitted values from the DHR
      model, we did not detect any remaining spatiotemporal correlation in the model's
      residuals. Using a DHR model and temperature data to account for the periodicity
      of prescribing proved to be an efficient way to capture its seasonal variation.
      The diagnostic procedures indicated that there was no need to model any remaining
      correlation explicitly.

PMID- 28453605
TI  - Outlier Practice Patterns in Mohs Micrographic Surgery: Defining the Problem and
      a Proposed Solution.
AB  - Importance: Outlier physician practices in health care can represent a
      significant burden to patients and the health system. Objective: To study outlier
      physician practices in Mohs micrographic surgery (MMS) and the associated
      factors. Design, Setting, and Participants: This retrospective analysis of
      publicly available Medicare Part B claims data from January 2012 to December 2014
      includes all physicians who received Medicare payments for MMS from any practice
      performing MMS on the head and neck, genitalia, hands, and feet region of
      Medicare Part B patients. Main Outcomes and Measures: Characteristics of outlier
      physicians, defined as those whose mean number of stages for MMS was 2 standard
      deviations greater than the mean number for all physicians billing MMS. Logistic
      regression was used to study the physician characteristics associated with
      outlier status. Results: Our analysis included 2305 individual billing physicians
      performing MMS. The mean number of stages per MMS case for all physicians
      practicing from January 2012 to December 2014 was 1.74, the median was 1.69, and
      the range was 1.09 to 4.11. Overall, 137 physicians who perform Mohs surgery were
      greater than 2 standard deviations above the mean (2 standard deviations above
      the mean = 2.41 stages per case) in at least 1 of the 3 examined years, and 49
      physicians (35.8%) were persistent high outliers in all 3 years. Persistent high
      outlier status was associated with performing Mohs surgery in a solo practice
      (odds ratio, 2.35; 95% CI, 1.25-4.35). Volume of cases per year, practice
      experience, and geographic location were not associated with persistent high
      outlier status. Conclusions and Relevance: Marked variation exists in the number
      of stages per case for MMS for head and neck, genitalia, hands, and feet skin
      cancers, which may represent an additional financial burden and unnecessary
      surgery on individual patients. Providing feedback to physicians may reduce
      unwarranted variation on this metric of quality.

PMID- 28453607
TI  - Determining the Best Strategies for Maternally Targeted Pertussis Vaccination
      Using an Individual-Based Model.
AB  - Rising pertussis incidence has prompted a number of countries to implement
      maternally targeted vaccination strategies to protect vulnerable infants, but
      questions remain about the optimal design of such strategies. We simulated
      pertussis transmission within an individual-based model parameterized to match
      Australian conditions, explicitly linking infants and their mothers to estimate
      the effectiveness of alternative maternally targeted vaccination strategies
      (antenatal delivery vs. postnatal delivery) and the benefit of revaccination over
      the course of multiple pregnancies. For firstborn infants aged less than 2
      months, antenatal immunization reduced annual pertussis incidence by 60%, from
      780 per 100,000 firstborn children under age 2 months (interquartile range (IQR),
      682-862) to 315 per 100,000 (IQR, 260-370), while postnatal vaccination produced
      a minimal reduction, with an incidence of 728 per 100,000 (IQR, 628-789).
      Subsequent infants obtained limited protection from a single antenatal dose, but
      revaccinating mothers during every pregnancy decreased incidence for these
      infants by 58%, from 1,878 per 100,000 subsequent children under age 2 months
      (IQR, 1,712-2,076) to 791 per 100,000 (IQR, 683-915). Subsequent infants also
      benefited from household-level herd immunity when antenatal vaccination for every
      pregnancy was combined with a toddler booster dose at age 18 months; incidence
      was reduced to 626 per 100,000 (IQR, 548-691). Our approach provides useful
      information to aid consideration of alternative maternally targeted vaccination
      strategies and can inform development of outcome measures for program evaluation.

PMID- 28453606
TI  - Determinants of Change in Objectively Assessed Sleep Duration Among Older Men.
AB  - We examined potential risk factors for changes in objectively assessed sleep
      duration within a large sample of community-dwelling older men. Participants (n =
      1,055; mean baseline age = 74.6 (standard deviation (SD), 4.7) years) had
      repeated ActiGraph assessments (ActiGraph LLC, Pensacola, Florida) taken at the
      baseline (2003-2005) and follow-up (2009-2012) waves of the Outcomes of Sleep
      Disorders in Older Men Study (an ancillary study to the Osteoporotic Fractures in
      Men (MrOS) Study conducted in 6 US communities). Among men with a baseline
      nighttime sleep duration of 5-8 hours, we assessed the odds of becoming a short
      duration (<5 hours) or long-duration (>8 hours) sleeper at follow-up. The odds of
      becoming a short-duration sleeper were higher among men with peripheral vascular
      disease (adjusted odds ratio (aOR) = 6.54, 95% confidence interval (CI): 2.30,
      18.55) and >=1 impairment in Instrumental Activities of Daily Living (IADL) (aOR
      = 2.57, 95% CI: 0.97, 6.78). The odds of becoming a long-duration sleeper were
      higher among those with greater baseline age (per SD increment, aOR = 1.49, 95%
      CI: 1.12, 2.00), depression symptoms (aOR = 3.13, 95% CI: 1.05, 9.36), and worse
      global cognitive performance (per SD increment of Modified Mini-Mental State
      Examination score, aOR = 0.74, 95% CI: 0.58, 0.94). Peripheral vascular disease
      and IADL impairment, but not chronological age, may be involved in the etiology
      of short sleep duration in older men. The risk factors for long-duration sleep
      suggest that deteriorating brain health predicts elongated sleep duration in
      older men.

PMID- 28453608
TI  - Time-Dependent Associations Between Body Composition, Physical Activity, and
      Current Asthma in Women: A Marginal Structural Modeling Analysis.
AB  - The role of obesity in adult asthma is well-known and has been partly attributed
      to a confounding role of physical inactivity. However, the interrelationships
      between obesity, physical activity, and asthma have been incompletely addressed,
      probably because their time-dependent and bidirectional nature represents a
      methodologically challenging research question. We aimed to estimate the
      independent causal effects of body mass index (BMI; weight (kg)/height (m)2) and
      physical activity on current asthma using marginal structural models (MSMs). MSMs
      were applied to 15,353 adult women from a 2011 case-control study of asthma
      (Asthma-E3N) nested within the French E3N study (Etude Epidemiologique aupres de
      Femmes de la Mutuelle Generale de l'Education Nationale). Three time periods
      (1997-2000-2002, 2000-2002-2005, and 2002-2005-2011) were defined, where
      exposures (BMI and physical activity) were measured at time t, outcome (current
      asthma) was measured at time t + 1, and covariates were measured at time t - 1 or
      at baseline. A strong significant and positive dose-response relationship between
      BMI and current asthma was observed (odds ratios were 0.90 (95% confidence
      interval (CI): 0.79, 1.03), 1.29 (95% CI: 1.17, 1.42), and 1.87 (95% CI: 1.60,
      2.18) for the BMI groups <20.0, 25.0-29.9, and >=30.0, respectively, versus the
      normal-weight group (BMI 20.0-24.9)). We found no association between physical
      activity and current asthma. Our results suggest an independent causal
      deleterious effect of overweight and obesity on current asthma, whereas no
      independent causal effect of physical activity was found.

PMID- 28453609
TI  - Invited Commentary: Searching for the Perfect Measure of Diastolic Dysfunction-A
      Futile Exercise?
AB  - Heart failure with preserved ejection fraction (HFpEF) is common, recalcitrant to
      treatment, and associated with poor outcomes. Diastolic dysfunction (DD) is an
      independent predictor of HFpEF risk, associated clinical manifestations, and long
      term outcomes. However, the usefulness of diastolic function assessment is
      limited by the heterogeneity in the existing definitions of DD. In this issue of
      the Journal, Rasmussen-Torvik et al. (Am J Epidemiol. 2017;185(12):1221-1227)
      have highlighted this problem by evaluating the prevalence and concordance of 4
      established definitions of DD in the Coronary Artery Risk Development in Young
      Adults (CARDIA) cohort. The authors demonstrate significant variability in
      prevalence of DD and its association with established risk factors across the
      different definitions. These findings suggest that the current 1-dimensional
      approach to HFpEF risk prediction based on noninvasive measures of diastolic
      function may not be optimal. Perhaps the future of HFpEF risk assessment lies in
      a multimodality approach that combines the relevant echocardiographic measures of
      diastolic function with blood-based biomarkers (such as N-terminal prohormone of
      brain natriuretic peptide (NT-proBNP)) and a measure of functional status (such
      as exercise capacity).

PMID- 28453610
TI  - The future of UK healthcare: problems and potential solutions to a system in
      crisis.
AB  - The UK's Health System is in crisis, central funding no longer keeping pace with
      demand. Traditional responses-spending more, seeking efficiency savings or
      invoking market forces-are not solutions. The health of our nation demands urgent
      delivery of a radical new model, negotiated openly between public, policymakers
      and healthcare professionals. Such a model could focus on disease prevention,
      modifying health behaviour and implementing change in public policy in fields
      traditionally considered unrelated to health such as transport, food and
      advertising. The true cost-effectiveness of healthcare interventions must be
      balanced against the opportunity cost of their implementation, bolstering the
      central role of NICE in such decisions. Without such action, the prognosis for
      our healthcare system-and for the health of the individuals it serves-may be
      poor. Here, we explore such a new prescription for our national health.

PMID- 28453611
TI  - modSaRa: a computationally efficient R package for CNV identification.
AB  - Summary: Chromosomal copy number variation (CNV) refers to a polymorphism that a
      DNA segment presents deletion or duplication in the population. The computational
      algorithms developed to identify this type of variation are usually of high
      computational complexity. Here we present a user-friendly R package, modSaRa,
      designed to perform copy number variants identification. The package is developed
      based on a change-point based method with optimal computational complexity and
      desirable accuracy. The current version of modSaRa package is a comprehensive
      tool with integration of preprocessing steps and main CNV calling steps.
      Availability and Implementation: modSaRa is an R package written in R, C ++ and
      Rcpp and is now freely available for download at
      http://c2s2.yale.edu/software/modSaRa . Contact: heping.zhang@yale.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28453612
TI  - Meiosis-specific proteins MEIOB and SPATA22 cooperatively associate with the
      single-stranded DNA-binding replication protein A complex and DNA double-strand
      breaks.
AB  - Meiotic recombination ensures faithful segregation of homologous chromosomes
      during meiosis and generates genetic diversity in gametes. MEIOB (meiosis
      specific with OB domains), a meiosis-specific single-stranded DNA-binding homolog
      of replication protein A1 (RPA1), is essential for meiotic recombination. Here,
      we investigated the molecular mechanisms of MEIOB by characterizing its binding
      partners spermatogenesis associated 22 (SPATA22) and RPA. We find that MEIOB and
      SPATA22 form an obligate complex and contain defined interaction domains. The
      interaction between these two proteins is unusual in that nearly any deletion in
      the binding domains abolishes the interaction. Strikingly, a single residue D383
      in MEIOB is indispensable for the interaction. The MEIOB/SPATA22 complex
      interacts with the RPA heterotrimeric complex in a collaborative manner.
      Furthermore, MEIOB and SPATA22 are recruited to induced DNA double-strand breaks
      (DSBs) together but not alone. These results demonstrate the cooperative property
      of the MEIOB-SPATA22 complex in its interaction with RPA and recruitment to DSBs.

PMID- 28453613
TI  - Functional Characterization of the Human Speech Articulation Network.
AB  - A number of brain regions have been implicated in articulation, but their precise
      computations remain debated. Using functional magnetic resonance imaging, we
      examine the degree of functional specificity of articulation-responsive brain
      regions to constrain hypotheses about their contributions to speech production.
      We find that articulation-responsive regions (1) are sensitive to articulatory
      complexity, but (2) are largely nonoverlapping with nearby domain-general regions
      that support diverse goal-directed behaviors. Furthermore, premotor articulation
      regions show selectivity for speech production over some related tasks
      (respiration control), but not others (nonspeech oral-motor [NSO] movements).
      This overlap between speech and nonspeech movements concords with
      electrocorticographic evidence that these regions encode articulators and their
      states, and with patient evidence whereby articulatory deficits are often
      accompanied by oral-motor deficits. In contrast, the superior temporal regions
      show strong selectivity for articulation relative to nonspeech movements,
      suggesting that these regions play a specific role in speech planning/production.
      Finally, articulation-responsive portions of posterior inferior frontal gyrus
      show some selectivity for articulation, in line with the hypothesis that this
      region prepares an articulatory code that is passed to the premotor cortex. Taken
      together, these results inform the architecture of the human articulation system.

PMID- 28453614
TI  - Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and
      follow-up.

PMID- 28453615
TI  - Do patient access schemes for high-cost cancer drugs deliver value to society?
      lessons from the NHS Cancer Drugs Fund.
AB  - Background: The NHS Cancer Drugs Fund (CDF) was established in 2010 to reduce
      delays and improve access to cancer drugs, including those that had been
      previously appraised but not approved by NICE (National Institute for Health and
      Care Excellence). After 1.3 billion GBP expenditure, a UK parliamentary review in
      2016 rationalized the CDF back into NICE. Methods: This paper analyses the
      potential value delivered by the CDF according to six value criteria. This
      includes validated clinical benefits scales, cost-effectiveness criteria as
      defined by NICE and an assessment of real-world data. The analysis focuses on 29
      cancer drugs approved for 47 indications that could be prescribed through the CDF
      in January 2015. Results: Of the 47 CDF approved indications, only 18 (38%)
      reported a statistically significant OS benefit, with an overall median survival
      of 3.1 months (1.4-15.7 months). When assessed according to clinical benefit
      scales, only 23 (48%) and 9 (18%) of the 47 drug indications met ASCO and ESMO
      criteria, respectively. NICE had previously rejected 26 (55%) of the CDF approved
      indications because they did not meet cost-effectiveness thresholds. Four drugs
      bevacizumab, cetuximab, everolimus and lapatinib-represented the bulk of CDF
      applications and were approved for a total of 18 separate indications. Thirteen
      of these indications were subsequently delisted by the CDF in January 2015 due to
      insufficient evidence for clinical benefit-data which were unchanged since their
      initial approval. Conclusions: We conclude the CDF has not delivered meaningful
      value to patients or society. There is no empirical evidence to support a 'drug
      only' ring fenced cancer fund relative to concomitant investments in other cancer
      domains such as surgery and radiotherapy, or other noncancer medicines.
      Reimbursement decisions for all drugs and interventions within cancer care should
      be made through appropriate health technology appraisal processes.

PMID- 28453616
TI  - Prevalence and Predictors of Diastolic Dysfunction According to Different
      Classification Criteria: The Coronary Artery Risk Development in Young in Adults
      Study.
AB  - Heart failure with preserved ejection fraction is often preceded by diastolic
      dysfunction (DD). Of several published DD criteria, it is unclear which, if any,
      are applicable to data obtained in epidemiologic cohorts. We evaluated the
      prevalence of DD using previously published definitions in a population-based
      study, the Coronary Artery Risk Development in Young Adults (CARDIA) Study, using
      data gathered in 2010-2011. Echocardiography was performed on 3,474 individuals
      (mean age = 50.2 years) at the CARDIA year 25 examination. Four published
      definitions of DD were studied. We calculated DD prevalence for each definition
      and determined the overlap between definitions. We used logistic regression to
      assess the strength of associations between demographic and clinical factors and
      the definitions of DD. Prevalence of DD ranged from 2% to 32% across the 4
      definitions, with a minority of cases identified by more than 1 definition. Two
      definitions classified 38%-39% of the study sample as indeterminate for DD.
      Associations of risk factors with DD varied considerably, with male sex being
      associated positively with DD for one definition (odds ratio = 1.4, 95%
      confidence interval: 1.2, 1.6) and inversely for another (odds ratio = 0.7, 95%
      confidence interval: 0.6, 0.8). Prevalence of DD varies markedly in CARDIA by the
      definition applied. A uniform, reliable, and accurate definition of DD for
      epidemiologic studies is needed.

PMID- 28453617
TI  - Clonal variation of human induced pluripotent stem cells for induction into the
      germ cell fate.
AB  - The mechanisms for human germ cell development have remained largely unknown, due
      to the difficulty in obtaining suitable experimental materials. The establishment
      of an in vitro system to reconstitute human germ cell development will thus
      provide a critical opportunity to understand its mechanisms at a molecular level.
      It has previously been shown that human induced pluripotent stem cells (hiPSCs)
      are first induced into incipient mesoderm-like cells (iMeLCs), which are in turn
      induced into primordial germ-cell like cells (PGCLCs) with gene expression
      properties similar to early migratory PGCs. Here, we report that the efficiency
      of PGCLC induction varies among hiPSC clones, and, interestingly, the clonal
      variations in PGCLC induction efficiency are reflected in the gene expression
      states of the iMeLCs. Remarkably, the expression levels of EOMES, MIXL1, or T in
      the iMeLCs are positively correlated with the efficiency of subsequent PGCLC
      generation, while the expressions of CDH1, SOX3, or FGF2 are negatively
      correlated. These results indicate that the expression changes of these genes
      occurring during iMeLC induction are key markers indicative of successful
      induction of PGCLCs, and furthermore, that hiPSC clones have different properties
      that influence their responsivity to the iMeLC induction. Our study thus provides
      important insights into the mechanism of hPGC specification as well as the
      development of a better strategy for inducing human germ cell fate from PSCs in
      vitro.

PMID- 28453618
TI  - Long-term effects of Class II Herbst treatment on the pharyngeal airway width.
AB  - Objective: The aim was to assess the long-term effects of Class II malocclusion
      treatment with the Herbst appliance on the pharyngeal airway (PA) width in
      comparison to untreated individuals with Classes I and II malocclusion. Methods:
      Lateral cephalometric radiographs of 13 male Class II patients from before (T1)
      and after (T2) treatment with the Herbst appliance as well as after the end of
      growth (T3) were retrospectively analyzed and compared to two untreated age- and
      gender-matched samples with Class I (n = 13) or Class II (n = 13) malocclusion.
      The PA dimensions were measured using the parameters p (narrowest distance
      between the soft palate and the posterior pharyngeal wall) and t (narrowest
      distance between the base of the tongue and the posterior pharyngeal wall). In
      addition, standard cephalometric measurements were performed. Results: Relevant
      changes in PA dimensions were only seen for the post-treatment period, during
      which the distances p and t showed a significant increase in the Herbst group
      only (?p: 2.3 mm, ?t: 3.3 mm) while remaining similar in both untreated groups
      (?p: 0.5 mm, ?t: 0.5 mm, respectively, ?p: 0.7 mm, ?t: 1.6 mm). During the same
      period, posterior face height showed a significantly larger increase in the
      Herbst group than in both control groups (8.2 versus 5.8 mm, respectively, 5.4
      mm), whereas anterior face height (NL-Me) showed a similar development in all
      groups (4.6 versus 4.4 mm, respectively 3.2 mm). Conclusion: In the long term,
      Herbst treatment resulted in a significant post-treatment increase of PA width,
      possibly due to an increased lower posterior facial height development compared
      to untreated individuals.

PMID- 28453619
TI  - Reply II. Cord blood androgen measurements: the importance of assay validation.

PMID- 28453620
TI  - CAVD: civilization aortic valve disease.

PMID- 28453621
TI  - Prevalence of malignant arrhythmia and sudden cardiac death in takotsubo syndrome
      and its management.
AB  - Aims: Recent studies have highlighted that takotsubo syndrome (TTS) is associated
      with a poor clinical outcome. Our study was conducted to determine the short- and
      long-term prevalence, recurrence rate and impact of life-threatening arrhythmias
      (LTA) on the clinical outcome of TTS. Methods and results: Our institutional
      database constituted a collective of 114 patients diagnosed with TTS between 2003
      and 2015. The patient groups, divided according to the presence (n = 13, 11.4%)
      or absence (n = 101, 88.6%) of LTAs, were followed-up over a period of 3 years so
      as to determine the clinical outcome. Our analyses suggest that patients
      comprising the LTA group suffered significantly more often from an acute
      cardiovascular event including cases of a newly diagnosed atrial fibrillation
      (38.4% vs. 2.9%), cardiogenic shock with use of inotropic agents (53.8% vs.
      14.8%) and cardiopulmonary resuscitation (61.5% vs. 1%). The short-term
      recurrence rate of a LTA episode was 15.3%, while the long-term recurrence rate
      of any LTA was around 5%. Whereas, in-hospital mortality was significantly higher
      in TTS associated with LTAs, the overall survival rate over 3 years was similar.
      A multivariate Cox regression analysis suggested atrial fibrillation, EF <= 35%,
      cardiogenic shock, and glomerular filtration rate <60 mL/min. as independent
      predictors of adverse outcome. Conclusion: The short- as well as the long-term
      prevalence and recurrence of LTAs in TTS patients is high. The long-term
      mortality rates were similar to the TTS patients presenting without any LTAs.
      LTAs in TTS could be triggered by a concomitant atrial fibrillation.

PMID- 28453622
TI  - The Impact of Exercise on Cancer Mortality, Recurrence, and Treatment-Related
      Adverse Effects.
AB  - The combination of an increasing number of new cancer cases and improving
      survival rates has led to a large and rapidly growing population with unique
      health-care requirements. Exercise has been proposed as a strategy to help
      address the issues faced by cancer patients. Supported by a growing body of
      research, major health organizations commonly identify the importance of
      incorporating exercise in cancer care and advise patients to be physically
      active. This systematic review comprehensively summarizes the available
      epidemiologic and randomized controlled trial evidence investigating the role of
      exercise in the management of cancer. Literature searches focused on determining
      the potential impact of exercise on 1) cancer mortality and recurrence and 2)
      adverse effects of cancer and its treatment. A total of 100 studies were reviewed
      involving thousands of individual patients whose exercise behavior was assessed
      following the diagnosis of any type of cancer. Compared with patients who
      performed no/less exercise, patients who exercised following a diagnosis of
      cancer were observed to have a lower relative risk of cancer mortality and
      recurrence and experienced fewer/less severe adverse effects. The findings of
      this review support the view that exercise is an important adjunct therapy in the
      management of cancer. Implications on cancer care policy and practice are
      discussed.

PMID- 28453623
TI  - Bayesian Inference of Allele-Specific Gene Expression Indicates Abundant Cis
      Regulatory Variation in Natural Flycatcher Populations.
AB  - Polymorphism in cis-regulatory sequences can lead to different levels of
      expression for the two alleles of a gene, providing a starting point for the
      evolution of gene expression. Little is known about the genome-wide abundance of
      genetic variation in gene regulation in natural populations but analysis of
      allele-specific expression (ASE) provides a means for investigating such
      variation. We performed RNA-seq of multiple tissues from population samples of
      two closely related flycatcher species and developed a Bayesian algorithm that
      maximizes data usage by borrowing information from the whole data set and
      combines several SNPs per transcript to detect ASE. Of 2,576 transcripts analyzed
      in collared flycatcher, ASE was detected in 185 (7.2%) and a similar frequency
      was seen in the pied flycatcher. Transcripts with statistically significant ASE
      commonly showed the major allele in >90% of the reads, reflecting that power was
      highest when expression was heavily biased toward one of the alleles. This would
      suggest that the observed frequencies of ASE likely are underestimates. The
      proportion of ASE transcripts varied among tissues, being lowest in testis and
      highest in muscle. Individuals often showed ASE of particular transcripts in more
      than one tissue (73.4%), consistent with a genetic basis for regulation of gene
      expression. The results suggest that genetic variation in regulatory sequences
      commonly affects gene expression in natural populations and that it provides a
      seedbed for phenotypic evolution via divergence in gene expression.

PMID- 28453625
TI  - Will you, nill you, I will treat you: the taming of lipoprotein(a).

PMID- 28453624
TI  - Inferring Rates and Length-Distributions of Indels Using Approximate Bayesian
      Computation.
AB  - The most common evolutionary events at the molecular level are single-base
      substitutions, as well as insertions and deletions (indels) of short DNA
      segments. A large body of research has been devoted to develop probabilistic
      substitution models and to infer their parameters using likelihood and Bayesian
      approaches. In contrast, relatively little has been done to model indel dynamics,
      probably due to the difficulty in writing explicit likelihood functions. Here, we
      contribute to the effort of modeling indel dynamics by presenting SpartaABC, an
      approximate Bayesian computation (ABC) approach to infer indel parameters from
      sequence data (either aligned or unaligned). SpartaABC circumvents the need to
      use an explicit likelihood function by extracting summary statistics from
      simulated sequences. First, summary statistics are extracted from the input
      sequence data. Second, SpartaABC samples indel parameters from a prior
      distribution and uses them to simulate sequences. Third, it computes summary
      statistics from the simulated sets of sequences. By computing a distance between
      the summary statistics extracted from the input and each simulation, SpartaABC
      can provide an approximation to the posterior distribution of indel parameters as
      well as point estimates. We study the performance of our methodology and show
      that it provides accurate estimates of indel parameters in simulations. We next
      demonstrate the utility of SpartaABC by studying the impact of alignment errors
      on the inference of positive selection. A C ++ program implementing SpartaABC is
      freely available in http://spartaabc.tau.ac.il.

PMID- 28453626
TI  - Protocol to monitor trade agreement food-related aspects: the Fiji case study.
AB  - Despite the growing rates of obesity and diet-related non-communicable diseases,
      globally, public health attention has only relatively recently turned to the
      links between trade agreements and the nutritional risks associated with it.
      Specific trade agreements appear to have played an influential role in the volume
      and types of foods entering different countries, yet there is currently no
      systematic and objective monitoring of trade agreements for their impacts on food
      environments. Recently, INFORMAS was set up to monitor and benchmark food
      environments, government policies and private sector actions within countries and
      globally. One of its projects/modules focuses on trade policy and in particular
      the food-related aspects of trade agreements. This paper describes the INFORMAS
      trade protocol, an approach to collecting food-related information about four
      domains of trade: trade in goods; trade in services and foreign direct
      investment; domestic supports, and policy space. Specifically, the protocol is
      tested in Fiji. The development and testing of this protocol in Fiji represents
      the first effort to set out a framework and process for objectively monitoring
      trade agreements and their impacts on national food supply and the wider food
      environment. It has shown that entry into WTO trade agreements contributed to the
      nutrition transition in Fiji through the increased availability of imported foods
      with varying nutritional quality. We observed an increase in imports of both
      healthy and less healthy foods. The application of the monitoring protocol also
      highlights challenges for data collection associated with each trade domain that
      should be considered for future data collection and analysis in other low and
      middle income countries.

PMID- 28453628
TI  - Post-transcriptional regulation of FUS and EWS protein expression by miR-141
      during neural differentiation.
AB  - Brain development involves proliferation, migration and specification of neural
      progenitor cells, culminating in neuronal circuit formation. Mounting evidence
      indicates that improper regulation of RNA binding proteins (RBPs), including
      members of the FET (FUS, EWS, TAF15) family, results in defective cortical
      development and/or neurodegenerative disorders. However, in spite of their
      physiological relevance, the precise pattern of FET protein expression in
      developing neurons is largely unknown. Herein, we found that FUS, EWS and TAF15
      expression is differentially regulated during brain development, both in time and
      in space. In particular, our study identifies a fine-tuned regulation of FUS and
      EWS during neuronal differentiation, whereas TAF15 appears to be more
      constitutively expressed. Mechanistically FUS and EWS protein expression is
      regulated at the post-transcriptional level during neuron differentiation and
      brain development. Moreover, we identified miR-141 as a key regulator of these
      FET proteins that modulate their expression levels in differentiating neuronal
      cells. Thus, our studies uncover a novel link between post-transcriptional
      regulation of FET proteins expression and neurogenesis.

PMID- 28453627
TI  - Patient-Reported Physical Function Measures in Cancer Clinical Trials.
AB  - Patient-reported outcomes (PROs) are increasingly used to monitor treatment
      related symptoms and physical function decrements in cancer clinical trials. As
      more patients enter survivorship, it is important to capture PRO physical
      function throughout trials to help restore pretreatment levels of function. We
      completed a systematic review of PRO physical function measures used in cancer
      clinical trials and evaluated their psychometric properties on the basis of
      guidelines from the US Food and Drug Administration. Five databases were searched
      through October 2015: PubMed/MEDLINE, EMBASE, CINAHL (Cumulative Index of Nursing
      and Allied Health Literature), Health and Psychosocial Instruments, and Cochrane.
      From an initial total of 10,233 articles, we identified 108 trials that captured
      PRO physical function. Within these trials, approximately 67% used the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      and 25% used the Medical Outcomes Study Short Form 36. Both the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      and Medical Outcomes Study Short Form 36 instruments generically satisfy most
      Food and Drug Administration requirements, although neither sought direct patient
      input as part of item development. The newer Patient-Reported Outcomes
      Measurement Information System physical function short form may be a brief,
      viable alternative. Clinicians should carefully consider the psychometric
      properties of these measures when incorporating PRO instrumentation into clinical
      trial design to provide a more comprehensive understanding of patient function.

PMID- 28453629
TI  - Long-term outcomes of a rapid deployment aortic valve: data up to 5 years.
AB  - OBJECTIVES: Rapid deployment aortic valve replacement (AVR) has been developed to
      facilitate minimally invasive approaches for cardiac surgery and shorten
      procedural times. TRITON is a prospectively designed study to assess safety and
      efficacy of rapid deployment AVR with Edwards INTUITY valve system. This report
      presents the 5-year outcomes of the TRITON trial. METHODS: A total of 295
      patients with aortic valve stenosis were enrolled in the TRITON trial and 287
      patients received the study valve. Procedural, early (<=30 days) and late (>30
      days) outcomes were collected. Valve haemodynamic performance was evaluated at
      specified time points by an independent Echocardiography Core Laboratory and
      clinical events adjudicated by an independent Clinical Events Committee. RESULTS:
      Mean age was 75.3 +/- 6.7 years. A total of 158 patients underwent isolated AVR
      and 129 patients underwent AVR with concomitant procedures. The 5-year survival
      rates were 85.7 +/- 3.4% and 75.2 +/- 4.9% for isolated AVR and concomitant AVR,
      respectively. Overall, freedom from valve-related death at 5 years was 98.2 +/-
      0.8%. At 5 years, the valve effective orifice area was 1.6 +/- 0.3 cm 2 , mean
      gradient was 10.5 +/- 5.4 mmHg and peak gradient was 18.9 +/- 9.3 mmHg.
      CONCLUSIONS: The 5-year outcomes of the TRITON trial demonstrate acceptable long
      term safety and excellent haemodynamic performance of rapid deployment AVR with
      the Edwards INTUITY valve system. ClinicalTrials.gov: NCT01445171.

PMID- 28453630
TI  - The Effects of CpG Densities around Transcription Start Sites on Sex-Biased Gene
      Expression in Poecilia reticulata.
AB  - As most genes are shared between females and males, DNA methylation is assumed to
      play a crucial role in sex-biased gene expression. DNA methylation exclusively
      occurs at CpG dinucleotides, and therefore, we would expect that CpG density
      around transcription start sites (TSSs) relate to sex-biased gene expression.
      Here we investigated the relationship between CpG densities around TSSs and the
      ratio of gene expression levels between sexes in the guppy (Poecilia reticulata),
      which displays remarkable sexual dimorphisms. We found that genes with sex-biased
      gene expression had different CpG densities downstream of TSSs compared with
      genes lacking sex-biased gene expression. Intriguingly, male-biased expression
      genes with intermediate CpG density downstream of TSSs exhibited greater
      differences in gene expression between sexes in the gonad and tail. Our findings
      suggested the possibility that CpGs around TSSs, especially in the downstream
      regions, play a crucial role in sex-biased gene expression through DNA
      methylation.

PMID- 28453632
TI  - Cord blood androgen measurements: the importance of assay validation.

PMID- 28453631
TI  - Prenatal cerebellar growth trajectories and the impact of periconceptional
      maternal and fetal factors.
AB  - STUDY QUESTION: CAN WE assess human prenatal cerebellar growth from the first
      until the third trimester of pregnancy and create growth trajectories to
      investigate associations with periconceptional maternal and fetal
      characteristics? SUMMARY ANSWER: Prenatal growth trajectories of the human
      cerebellum between 9 and 32 weeks gestational age (GA) were created using three
      dimensional ultrasound (3D-US) and show negative associations with pre-pregnancy
      and early first trimester BMI calculated from self-reported and standardized
      measured weight and height, respectively. WHAT IS KNOWN ALREADY: The cerebellum
      is essential for normal neurodevelopment and abnormal cerebellar development has
      been associated with neurodevelopmental impairments and psychiatric diseases.
      Cerebellar development is particularly susceptible to exposures during the
      prenatal period, including maternal folate status, smoking habit and alcohol
      consumption. STUDY DESIGN, SIZE, DURATION: From 2013 until 2015, we included 182
      singleton pregnancies during the first trimester as a subgroup in a prospective
      periconception cohort with follow-up until birth. For the statistical analyses,
      we selected 166 pregnancies ending in live born infants without congenital
      malformations. PARTICIPANTS/MATERIALS, SETTING, METHODS: We measured
      transcerebellar diameter (TCD) at 9, 11, 22, 26 and 32 weeks GA on ultrasound
      scans. Growth rates were calculated and growth trajectories of the cerebellum
      were created. Linear mixed models were used to estimate associations between
      cerebellar growth and maternal age, parity, mode of conception, geographic
      origin, pre-pregnancy and first trimester BMI, periconceptional smoking, alcohol
      consumption, timing of folic acid supplement initiation and fetal gender. MAIN
      RESULTS AND THE ROLE OF CHANCE: In total, 166 pregnancies provided 652 (87%)
      ultrasound images eligible for TCD measurements. Cerebellar growth rates
      increased with advancing GA being 0.1691 mm/day in the first trimester, 0.2336
      mm/day in the second trimester and 0.2702 mm/day in the third trimester. Pre
      pregnancy BMI, calculated from self-reported body weight and height, was
      significantly associated with decreased cerebellar growth trajectories (beta = 
      0.0331 mm, 95% CI = -0.0638; -0.0024, P = 0.035). A similar association was found
      between cerebellar growth trajectories and first trimester BMI, calculated from
      standardized measurements of body weight and height (beta = -0.0325, 95% CI = 
      0.0642; -0.0008, P = 0.045, respectively). LIMITATIONS, REASONS FOR CAUTION: As
      the study population largely consisted of tertiary hospital patients, external
      validity should be studied in the general population. Whether small differences
      in prenatal cerebellar growth due to a higher pre-pregnancy and first trimester
      BMI have consequences for neurodevelopmental outcome needs further investigation.
      WIDER IMPLICATIONS OF THE FINDINGS: Our findings further substantiate previous
      evidence for the detrimental impact of a higher maternal BMI on
      neurodevelopmental health of offspring in later life. STUDY FUNDING/COMPETING
      INTEREST(S): This study was funded by the Department of Obstetrics and
      Gynecology, Erasmus MC University Medical Centre and Sophia Children's Hospital
      Fund, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests
      are declared.

PMID- 28453633
TI  - Role of DNA gyrase and topoisomerase IV mutations in fluoroquinolone resistance
      of Capnocytophaga spp. clinical isolates and laboratory mutants.
AB  - Objectives: Capnocytophaga spp. are often reported to cause bacteraemia and extra
      oral infections and are characterized by their significant contribution to
      resistance to beta-lactam and macrolide-lincosamide-streptogramin antibiotics in
      the human oral microbiota. The implication of mutations in the quinolone
      resistance-determining region (QRDR) of DNA gyrase A and B ( gyrA and gyrB ) and
      topoisomerase IV ( parC and parE ) of fluoroquinolone (FQ)-resistant
      Capnocytophaga spp., hitherto unknown, was explored in this study. Methods: Two
      reference strains ( Capnocytophaga gingivalis ATCC 33624 and Capnocytophaga
      sputigena ATCC 33612) and four Capnocytophaga spp. isolated from clinical samples
      were studied. Nine in vitro FQ-resistant mutants, derived from two reference
      strains and one FQ-susceptible clinical isolate, were selected by successive
      inoculations onto medium containing levofloxacin. MICs of ofloxacin, norfloxacin,
      ciprofloxacin, levofloxacin and moxifloxacin were determined. The presumed QRDRs
      of GyrA, GyrB, ParC and ParE from Capnocytophaga spp. were determined by sequence
      homology to Bacteroides fragilis and Escherichia coli . PCR primers were designed
      to amplify the presumed QRDR genetic region of Capnocytophaga spp. and sequence
      analyses were performed using the BLAST program at the National Center for
      Biotechnology Information. Results and conclusions: gyrA mutations leading to a
      substitution from amino acid position 80 to 86 were systematically detected in
      Capnocytophaga spp. with ciprofloxacin MIC >1 mg/L and considered as the primary
      target of FQs. No mutational alteration in the QRDR of gyrB was detected. Other
      mutations in parC and parE led to spontaneous amino acid substitutions of DNA
      topoisomerase IV subunit B with no alteration in FQ susceptibility.

PMID- 28453635
TI  - Peak Bone Mass and Bone Microarchitecture in Adults Born With Low Birth Weight
      Preterm or at Term: A Cohort Study.
AB  - Context and Objectives: Peak bone mass (PBM) is regarded as the most important
      determinant of osteoporosis. Growing evidence suggests a role of intrauterine
      programming in skeletal development. We examined PBM and trabecular bone score
      (TBS) in adults born preterm with very low birth weight (VLBW) or small for
      gestational age (SGA) at term compared with term-born controls. Design, Setting,
      Participants, and Outcomes: This follow-up cohort study included 186 men and
      women (25 to 28 years); 52 preterm VLBW (<=1500 g), 59 term-born SGA (<10th
      percentile), and 75 controls (>10th percentile). Main outcome was bone mineral
      density (BMD) by dual x-ray absorptiometry. Secondary outcomes were bone mineral
      content (BMC), TBS, and serum bone markers. Results: VLBW adults had lower BMC
      and BMD vs controls, also when adjusted for height, weight, and potential
      confounders, with the following BMD Z-score differences: femoral neck, 0.6
      standard deviation (SD) (P = 0.003); total hip, 0.4 SD (P = 0.01); whole body,
      0.5 SD (P = 0.007); and lumbar spine, 0.3 SD (P = 0.213). The SGA group displayed
      lower spine BMC and whole-body BMD Z-scores, but not after adjustment. Adjusted
      odds ratios for osteopenia/osteoporosis were 2.4 and 2.0 in VLBW and SGA adults,
      respectively. TBS did not differ between groups, but it was lower in men than in
      women. Serum Dickkopf-1 was higher in VLBW subjects vs controls; however, it was
      not significant after adjustment for multiple comparisons. Conclusions: Both low
      birth-weight groups displayed lower PBM and higher frequency of
      osteopenia/osteoporosis, implying increased future fracture risk. The most
      pronounced bone deficit was seen in VLBW adults.

PMID- 28453634
TI  - Recent Sex Chromosome Divergence despite Ancient Dioecy in the Willow Salix
      viminalis.
AB  - Sex chromosomes can evolve when recombination is halted between a pair of
      chromosomes, and this can lead to degeneration of the sex-limited chromosome. In
      the early stages of differentiation sex chromosomes are homomorphic, and even
      though homomorphic sex chromosomes are very common throughout animals and plants,
      we know little about the evolutionary forces shaping these types of sex
      chromosomes. We used DNA- and RNA-Seq data from females and males to explore the
      sex chromosomes in the female heterogametic willow, Salix viminalis, a species
      with ancient dioecy but with homomorphic sex chromosomes. We detected no major
      sex differences in read coverage in the sex determination (SD) region, indicating
      that the W region has not significantly degenerated. However, single nucleotide
      polymorphism densities in the SD region are higher in females compared with
      males, indicating very recent recombination suppression, followed by the
      accumulation of sex-specific single nucleotide polymorphisms. Interestingly, we
      identified two female-specific scaffolds that likely represent W-chromosome
      specific sequence. We show that genes located in the SD region display a mild
      excess of male-biased expression in sex-specific tissue, and we use allele
      specific gene expression analysis to show that this is the result of
      masculinization of expression on the Z chromosome rather than degeneration of
      female-expression on the W chromosome. Together, our results demonstrate that
      insertion of small DNA fragments and accumulation of sex-biased gene expression
      can occur before the detectable decay of the sex-limited chromosome.

PMID- 28453636
TI  - Vitamin D status and all-cause mortality in patients with chronic kidney disease:
      A systematic review and dose-response meta-analysis.
AB  - Context: Prevalence of vitamin D deficiency is high in patients with chronic
      kidney disease. Less attention has been paid to measurement and correction of
      serum level of 25(OH)D in these patients. Objective: We examined the association
      between different levels of serum 25(OH)D and risk of all-cause mortality in
      patients with chronic kidney disease. Data sources: Systematic search were done
      using MedLine and EMBASE from inception up to November 2016. Reference lists of
      all relevant articles and reviews also were searched. Study selection:
      Prospective or retrospective cohort studies that reported risk estimates of all
      cause mortality for three or more categories of serum 25(OH)D in patients with
      chronic kidney disease were selected. Studies that reported results as
      continuously also were included. Two independent investigators screened and
      selected the articles. Of 1281 identified studies, 13 prospective cohorts, two
      retrospective cohorts and one nested case-control study with 17053 patients and
      7517 incident death were included. Data Extraction: Two independent authors
      extracted data from included studies. Any discrepancies were resolved through
      consensus. Data Synthesis: Reported risk estimates were combined using a random
      effects model. Summary risk estimates of all-cause mortality were1.63 (95%CI:
      1.32, 1.94) for severe deficiency (<10 ng/ml), 1.22 (95%CI: 1.09, 1.35) for mild
      deficiency (10-20 ng/ml) and 1.12 (95%CI: 1.06, 1.18) for insufficiency (20-30
      ng/ml). Results were more evident in dialysis dependent patients. 10 ng/ml
      increment in serum 25(OH)D was associated with 21% reduction in the risk of
      overall mortality (RR: 0.79, 95%CI: 0.70, 0.87).Lower risk of all-cause mortality
      was observed at serum 25(OH)D about 25 to 30 ng/ml. Dialysis treatment was one of
      the sources of variation between studies. Conclusions: Higher levels of serum
      25(OH) D were associated with lower risk of all-cause mortality in patients with
      chronic kidney disease, but concerning serum levels more than 35 ng/mL we have no
      conclusive evidence.

PMID- 28453637
TI  - Automated identification of implausible values in growth data from pediatric
      electronic health records.
AB  - Objective: Large electronic health record (EHR) datasets are increasingly used to
      facilitate research on growth, but measurement and recording errors can lead to
      biased results. We developed and tested an automated method for identifying
      implausible values in pediatric EHR growth data. Materials and Methods: Using
      deidentified data from 46 primary care sites, we developed an algorithm to
      identify weight and height values that should be excluded from analysis,
      including implausible values and values that were recorded repeatedly without
      remeasurement. The foundation of the algorithm is a comparison of each
      measurement, expressed as a standard deviation score, with a weighted moving
      average of a child's other measurements. We evaluated the performance of the
      algorithm by (1) comparing its results with the judgment of physician reviewers
      for a stratified random selection of 400 measurements and (2) evaluating its
      accuracy in a dataset with simulated errors. Results: Of 2 000 595 growth
      measurements from 280 610 patients 1 to 21 years old, 3.8% of weight and 4.5% of
      height values were identified as implausible or excluded for other reasons. The
      proportion excluded varied widely by primary care site. The automated method had
      a sensitivity of 97% (95% confidence interval [CI], 94-99%) and a specificity of
      90% (95% CI, 85-94%) for identifying implausible values compared to physician
      judgment, and identified 95% (weight) and 98% (height) of simulated errors.
      Discussion and Conclusion: This automated, flexible, and validated method for
      preparing large datasets will facilitate the use of pediatric EHR growth datasets
      for research.

PMID- 28453638
TI  - EtG/EtS in Serum by UHPLC-MS-MS in Suspected Sexual Assault Cases.
AB  - A method including semi-automated extraction of ethyl glucuronide (EtG) and ethyl
      sulfate (EtS) from serum followed by ultra-performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS-MS) has been developed and validated. Sample
      preparation prior to UHPLC-MS-MS analysis consisted of protein precipitation and
      filtration through a phospholipid removal plate. Chromatography was achieved
      using an HSS T3 column and gradient elution with formic acid in water in
      combination with methanol. The mass spectrometer was monitored in the negative
      mode with multiple reaction monitoring. Two transitions were monitored for the
      analytes and one for the deuterated internal standards (ISs). The limits of
      quantification were 0.025 mg/L for EtG and 0.009 mg/L for EtS. The between-assay
      relative standard deviations were in the range of 3.8-9.1%, the recovery was 66
      102% and matrix effects ranged from 88 to 97% (corrected with IS). Compared to
      previously published studies, the method presented is semi-automated, uses a
      simple method for phospholipid removal and has short run times and low limit of
      quantifications. We analyzed serum samples from 49 female patients presenting to
      the Sexual Assault Centre at St. Olav University Hospital in Trondheim, Norway,
      for ethanol, EtG and EtS. EtG and EtS were detected longer than ethanol itself
      after intake of ethanol, with estimated maximum detection times of >24 h. The
      ethanol, EtG and EtS concentrations were highly correlated (P < 0.001), but with
      large inter-individual variations. This study suggests that analysis of EtG and
      EtS in serum or blood may complement ethanol analysis and shed light on the
      patient's recent ethanol intake after ethanol itself is no longer detectable.

PMID- 28453640
TI  - Pioneering topological methods for network-based drug-target prediction by
      exploiting a brain-network self-organization theory.
AB  - The bipartite network representation of the drug-target interactions (DTIs) in a
      biosystem enhances understanding of the drugs' multifaceted action modes,
      suggests therapeutic switching for approved drugs and unveils possible side
      effects. As experimental testing of DTIs is costly and time-consuming,
      computational predictors are of great aid. Here, for the first time, state-of-the
      art DTI supervised predictors custom-made in network biology were compared-using
      standard and innovative validation frameworks-with unsupervised pure topological
      based models designed for general-purpose link prediction in bipartite networks.
      Surprisingly, our results show that the bipartite topology alone, if adequately
      exploited by means of the recently proposed local-community-paradigm (LCP) theory
      initially detected in brain-network topological self-organization and afterwards
      generalized to any complex network-is able to suggest highly reliable
      predictions, with comparable performance with the state-of-the-art-supervised
      methods that exploit additional (non-topological, for instance biochemical) DTI
      knowledge. Furthermore, a detailed analysis of the novel predictions revealed
      that each class of methods prioritizes distinct true interactions; hence,
      combining methodologies based on diverse principles represents a promising
      strategy to improve drug-target discovery. To conclude, this study promotes the
      power of bio-inspired computing, demonstrating that simple unsupervised rules
      inspired by principles of topological self-organization and adaptiveness arising
      during learning in living intelligent systems (like the brain) can efficiently
      equal perform complicated algorithms based on advanced, supervised and knowledge
      based engineering.

PMID- 28453639
TI  - Perioperative morbidity and mortality of octogenarians treated by radical
      cystectomy-a multi-institutional retrospective study in Japan.
AB  - Objective: To determine the characteristics of 90-day morbidity and mortality
      after radical cystectomy in Japanese octogenarians. Methods: A retrospective
      multi-institutional study. We reviewed the records of 834 patients treated by
      open radical cystectomy between 1997 and 2010. All complications within 90 days
      after surgery were sorted into the 11 categories proposed by the Memorial Sloan
      Kettering Cancer Center and graded according to the modified Clavien-Dindo
      system. We compared the characteristics of complications between >=80-year (n =
      86) and <80-year (n = 748) groups. Multivariate regression models were used to
      determine the predictors of complications. Results: American Society of
      Anesthesiologists score III-IV was more frequent (14% vs. 6%, respectively, P <
      0.0001), and ureterocutaneostomy was more frequently performed (30% vs. 21%,
      respectively, P = 0.0148) in the >=80-year group compared with <80-year group.
      There were no significant differences in the rates of any complication, major
      (Grade 3-5) complication, or 90-day mortality between the two groups (>=80-year
      group: 70%, 21%, 3.5%, respectively, <80-year group: 68%, 22%, 2%, respectively).
      The >=80-year group had fewer genitourinary complications (7% vs. 16%,
      respectively, P = 0.0131). Multivariate regression analyses revealed that bowel
      using urinary diversion (P = 0.0031) and the operative time (P = 0.0269) were
      significant predictors of any grade of complications, and a male sex (P =
      0.0167), annual cystectomy volume (P = 0.0284) and prior cardiovascular
      comorbidity (P = 0.0034) were significant predictors of major complications.
      Conclusions: In our experience, radical cystectomy in Japanese octogenarians
      caused similar perioperative comorbidities. Old age as a single criterion should
      not be used to abandon radical cystectomy; careful preoperative assessment is
      mandatory.

PMID- 28453641
TI  - Phenotypic and Genetic Analysis of the Leopard Complex Spotting in Noriker
      Horses.
AB  - Genetic analyses of coat colors are frequently restricted to subjectively
      categorized phenotype information. The aim of this study was to develop a method
      to numerically quantify the variability of leopard complex (LP) spotting
      phenotypes introducing tools from image analysis. Generalized Procrustes analysis
      eliminates systematic errors due to imaging process. The binarization of
      normalized images and the application of principal component analysis (PCA) on
      the derived pixel matrices, transform pixel information into numerical data
      space. We applied these methods on 90 images to ascertain the specific leopard
      patterns within the Noriker breed. Furthermore, we genotyped a representative
      sample of 191 Noriker horses for the known LP spotting associated loci. Ninety
      seven percentage of the genotyped leopard spotted horses were heterozygous for LP
      and had at least one copy of the PATN1 allele. However, the remaining pattern
      variation was great, indicating other genetic factors influencing the expression
      of LP spotting. Based upon this data, we estimated effect sizes of the modifier
      PATN1, and additional factors including sex, age, base color, and spotting
      phenotype of parents. The PCA of the pixel matrix resulted in 2 significant
      components accounting for 51% of the variation. Applying a linear model, we
      identified significant effects for age groups and base color on the first and
      second components, while for sex and parents' LP phenotype significant effects
      were found on 4 additional components.

PMID- 28453642
TI  - Facilitation of Contextual Fear Extinction by Orexin-1 Receptor Antagonism Is
      Associated with the Activation of Specific Amygdala Cell Subpopulations.
AB  - Background: Orexins are hypothalamic neuropeptides recently involved in the
      regulation of emotional memory. The basolateral amygdala, an area orchestrating
      fear memory processes, appears to be modulated by orexin transmission during fear
      extinction. However, the neuronal types within the basolateral amygdala involved
      in this modulation remain to be elucidated. Methods: We used retrograde tracing
      combined with immunofluorescence techniques in mice to identify basolateral
      amygdala projection neurons and cell subpopulations in this brain region
      influenced by orexin transmission during contextual fear extinction
      consolidation. Results: Treatment with the orexin-1 receptor antagonist SB334867
      increased the activity of basolateral amygdala neurons projecting to infralimbic
      medial prefrontal cortex during fear extinction. GABAergic interneurons
      expressing calbindin, but not parvalbumin, were also activated by orexin-1
      receptor antagonism in the basolateral amygdala. Conclusions: These data identify
      neuronal circuits and cell populations of the amygdala associated with the
      facilitation of fear extinction consolidation induced by the orexin-1 receptor
      antagonist SB334867.

PMID- 28453644
TI  - TraitRateProp: a web server for the detection of trait-dependent evolutionary
      rate shifts in sequence sites.
AB  - Understanding species adaptation at the molecular level has been a central goal
      of evolutionary biology and genomics research. This important task becomes
      increasingly relevant with the constant rise in both genotypic and phenotypic
      data availabilities. The TraitRateProp web server offers a unique perspective
      into this task by allowing the detection of associations between sequence
      evolution rate and whole-organism phenotypes. By analyzing sequences and
      phenotypes of extant species in the context of their phylogeny, it identifies
      sequence sites in a gene/protein whose evolutionary rate is associated with
      shifts in the phenotype. To this end, it considers alternative histories of whole
      organism phenotypic changes, which result in the extant phenotypic states. Its
      joint likelihood framework that combines models of sequence and phenotype
      evolution allows testing whether an association between these processes exists.
      In addition to predicting sequence sites most likely to be associated with the
      phenotypic trait, the server can optionally integrate structural 3D information.
      This integration allows a visual detection of trait-associated sequence sites
      that are juxtapose in 3D space, thereby suggesting a common functional role. We
      used TraitRateProp to study the shifts in sequence evolution rate of the RPS8
      protein upon transitions into heterotrophy in Orchidaceae. TraitRateProp is
      available at http://traitrate.tau.ac.il/prop.

PMID- 28453643
TI  - Early-Onset Obesity: Unrecognized First Evidence for GNAS Mutations and
      Methylation Changes.
AB  - Context: Early-onset obesity, characteristic for disorders affecting the leptin
      melanocortin pathway, is also observed in pseudohypoparathyroidism type 1A
      (PHP1A), a disorder caused by maternal GNAS mutations that disrupt expression or
      function of the stimulatory G protein alpha-subunit (Gsalpha). Mutations and/or
      epigenetic abnormalities at the same genetic locus are also the cause of
      pseudohypoparathyroidism type 1B (PHP1B). However, although equivalent
      biochemical and radiographic findings can be encountered in these related
      disorders caused by GNAS abnormalities, they are considered distinct clinical
      entities. Objectives: To further emphasize the overlapping features between both
      disorders, we report the cases of several children, initially brought to medical
      attention because of unexplained early-onset obesity, in whom PHP1B or PHP1A was
      eventually diagnosed. Patients and Methods: Search for GNAS methylation changes
      or mutations in cohorts of patients with early-onset obesity. Results: Severe
      obesity had been noted in five infants, with a later diagnosis of PHP1B due to
      STX16 deletions and/or abnormal GNAS methylation. These findings prompted
      analysis of 24 unselected obese patients, leading to the discovery of inherited
      STX16 deletions in 2 individuals. Similarly, impressive early weight gains were
      noted in five patients, who initially lacked additional Albright hereditary
      osteodystrophy features but in whom PHP1A due to GNAS mutations involving exons
      encoding Gsalpha was diagnosed. Conclusions: Obesity during the first year of
      life can be the first clinical evidence for PHP1B, expanding the spectrum of
      phenotypic overlap between PHP1A and PHP1B. Importantly, GNAS methylation
      abnormalities escape detection by targeted or genome-wide sequencing strategies,
      raising the question of whether epigenetic GNAS analyses should be considered for
      unexplained obesity.

PMID- 28453645
TI  - Medicare Part D Payments for Topical Steroids: Rising Costs and Potential
      Savings.
AB  - Importance: Rising pharmaceutical costs in the United States are an increasing
      source of financial burden for payers and patients. Although topical steroids are
      among the most commonly prescribed medications in dermatology, there are limited
      data on steroid-related spending and utilization. Objective: To characterize
      Medicare and patient out-of-pocket costs for topical steroids, and to model
      potential savings that could result from substitution of the cheapest topical
      steroid from the corresponding potency class. Design, Setting, and Participants:
      This study was a retrospective cost analysis of the Medicare Part D Prescriber
      Public Use File, which details annual drug utilization and spending on both
      generic and branded drugs from 2011 to 2015 by Medicare Part D participants who
      filled prescriptions for topical steroids. Main Outcomes and Measures: Total and
      potential Medicare and out-of-pocket patient spending. Costs were adjusted for
      inflation and reported in 2015 dollars. Results: Medicare Part D expenditures on
      topical steroids between 2011 and 2015 were $2.3 billion. Patients' out-of-pocket
      spending for topical steroids over the same period was $333.7 million. The total
      annual spending increased from $237.6 million to $775.9 million, an increase of
      226.5%. Patients' annual out-of-pocket spending increased from $41.4 million to
      $101.8 million, an increase of 145.9%. The total number of prescriptions were 7.7
      million in 2011 and 10.6 million in 2015, an increase of 37.0%. Generic
      medication costs accounted for 97.8% of the total spending during this time
      period. The potential health care savings and out-of-pocket patient savings from
      substitution of the cheapest topical steroid within the corresponding potency
      class were $944.8 million and $66.6 million, respectively. Conclusions and
      Relevance: Most topical steroids prescribed were generic drugs. There has been a
      sharp increase in Medicare and out-of-pocket spending on topical steroids that is
      driven by higher costs for generics. Use of clinical decision support tools to
      enable substitution of the most affordable generic topical steroid from the
      corresponding potency class may reduce drug expenditures.

PMID- 28453646
TI  - Protecting Confidentiality in Cancer Registry Data With Geographic Identifiers.
AB  - The National Cancer Institute's Surveillance, Epidemiology, and End Results
      Program releases research files of cancer registry data. These files include
      geographic information at the county level, but no finer. Access to finer
      geography, such as census tract identifiers, would enable richer analyses-for
      example, examination of health disparities across neighborhoods. To date, tract
      identifiers have been left off the research files because they could compromise
      the confidentiality of patients' identities. We present an approach to inclusion
      of tract identifiers based on multiply imputed, synthetic data. The idea is to
      build a predictive model of tract locations, given patient and tumor
      characteristics, and randomly simulate the tract of each patient by sampling from
      this model. For the predictive model, we use multivariate regression trees fitted
      to the latitude and longitude of the population centroid of each tract. We
      implement the approach in the registry data from California. The method results
      in synthetic data that reproduce a wide range (but not all) of analyses of census
      tract socioeconomic cancer disparities and have relatively low disclosure risks,
      which we assess by comparing individual patients' actual and synthetic tract
      locations. We conclude with a discussion of how synthetic data sets can be used
      by researchers with cancer registry data.

PMID- 28453647
TI  - Photosynthetic acclimation to warming in tropical forest tree seedlings.
AB  - Tropical forests have a mitigating effect on man-made climate change by acting as
      a carbon sink. For that effect to continue, tropical trees will have to acclimate
      to rising temperatures, but it is currently unknown whether they have this
      capacity. We grew seedlings of three tropical tree species over a range of
      temperature regimes (TGrowth = 25, 30, 35  degrees C) and measured the
      temperature response of photosynthetic CO2 uptake. All species showed signs of
      acclimation: the temperature-response curves shifted, such that the temperature
      at which photosynthesis peaked (TOpt) increased with increasing TGrowth. However,
      although TOpt shifted, it did not reach TGrowth at high temperature, and this
      difference between TOpt and TGrowth increased with increasing TGrowth, indicating
      that plants were operating at supra-optimal temperatures for photosynthesis when
      grown at high temperatures. The high-temperature CO2 compensation point did not
      increase with TGrowth. Hence, temperature-response curves narrowed with
      increasing TGrowth. TOpt correlated with the ratio of the RuBP regeneration
      capacity over the RuBP carboxylation capacity, suggesting that at high TGrowth
      photosynthetic electron transport rate associated with RuBP regeneration had
      greater control over net photosynthesis. The results show that although
      photosynthesis of tropical trees can acclimate to moderate warming, carbon gain
      decreases with more severe warming.

PMID- 28453648
TI  - Recent advances in sequence assembly: principles and applications.
AB  - The application of advanced sequencing technologies and the rapid growth of
      various sequence data have led to increasing interest in DNA sequence assembly.
      However, repeats and polymorphism occur frequently in genomes, and each of these
      has different impacts on assembly. Further, many new applications for sequencing,
      such as metagenomics regarding multiple species, have emerged in recent years.
      These not only give rise to higher complexity but also prevent short-read
      assembly in an efficient way. This article reviews the theoretical foundations
      that underlie current mapping-based assembly and de novo-based assembly, and
      highlights the key issues and feasible solutions that need to be considered. It
      focuses on how individual processes, such as optimal k-mer determination and
      error correction in assembly, rely on intelligent strategies or high-performance
      computation. We also survey primary algorithms/software and offer a discussion on
      the emerging challenges in assembly.

PMID- 28453649
TI  - PMut: a web-based tool for the annotation of pathological variants on proteins,
      2017 update.
AB  - We present here a full update of the PMut predictor, active since 2005 and with a
      large acceptance in the field of predicting Mendelian pathological mutations.
      PMut internal engine has been renewed, and converted into a fully featured
      standalone training and prediction engine that not only powers PMut web portal,
      but that can generate custom predictors with alternative training sets or
      validation schemas. PMut Web portal allows the user to perform pathology
      predictions, to access a complete repository of pre-calculated predictions, and
      to generate and validate new predictors. The default predictor performs with good
      quality scores (MCC values of 0.61 on 10-fold cross validation, and 0.42 on a
      blind test with SwissVar 2016 mutations). The PMut portal is freely accessible at
      http://mmb.irbbarcelona.org/PMut. A complete help and tutorial is available at
      http://mmb.irbbarcelona.org/PMut/help.

PMID- 28453650
TI  - plantiSMASH: automated identification, annotation and expression analysis of
      plant biosynthetic gene clusters.
AB  - Plant specialized metabolites are chemically highly diverse, play key roles in
      host-microbe interactions, have important nutritional value in crops and are
      frequently applied as medicines. It has recently become clear that plant
      biosynthetic pathway-encoding genes are sometimes densely clustered in specific
      genomic loci: biosynthetic gene clusters (BGCs). Here, we introduce plantiSMASH,
      a versatile online analysis platform that automates the identification of
      candidate plant BGCs. Moreover, it allows integration of transcriptomic data to
      prioritize candidate BGCs based on the coexpression patterns of predicted
      biosynthetic enzyme-coding genes, and facilitates comparative genomic analysis to
      study the evolutionary conservation of each cluster. Applied on 48 high-quality
      plant genomes, plantiSMASH identifies a rich diversity of candidate plant BGCs.
      These results will guide further experimental exploration of the nature and
      dynamics of gene clustering in plant metabolism. Moreover, spurred by the
      continuing decrease in costs of plant genome sequencing, they will allow genome
      mining technologies to be applied to plant natural product discovery. The
      plantiSMASH web server, precalculated results and source code are freely
      available from http://plantismash.secondarymetabolites.org.

PMID- 28453651
TI  - A PanorOmic view of personal cancer genomes.
AB  - The massive molecular profiling of thousands of cancer patients has led to the
      identification of many tumor type specific driver genes. However, only a few (or
      none) of them are present in each individual tumor and, to enable precision
      oncology, we need to interpret the alterations found in a single patient. Cancer
      PanorOmics (http://panoromics.irbbarcelona.org) is a web-based resource to
      contextualize genomic variations detected in a personal cancer genome within the
      body of clinical and scientific evidence available for 26 tumor types, offering
      complementary cohort- and patient-centric views. Additionally, it explores the
      cellular environment of mutations by mapping them on the human interactome and
      providing quasi-atomic structural details, whenever available. This 'PanorOmic'
      molecular view of individual tumors, together with the appropriate genetic
      counselling and medical advice, should contribute to the identification of
      actionable alterations ultimately guiding the clinical decision-making process.

PMID- 28453652
TI  - MHC-B variability within the Finnish Landrace chicken conservation program.
AB  - The major histocompatibility complex (MHC) is a cluster of genes involved with
      immune responses. The chicken MHC has been shown to influence resistance to
      viruses, bacteria, and infections from both internal and external parasites. The
      highly variable chicken MHC haplotypes were initially identified by the use of
      haplotype-specific serological reagents. A novel SNP-based panel encompassing
      210,000 bp of the MHC-B locus was developed to allow fine scale genetic analyses
      including rapid identification of novel haplotypes for which serological reagents
      are not available. The Finnish Landrace breed of chickens traces its origins to
      almost 1,000 years ago, with multiple lineages maintained as small populations in
      isolated villages. The breed is well adapted to the cooler Finnish climate and is
      considered to be an infrequent egg layer. Conservation efforts to protect this
      endangered breed were initiated by a hobby breeder in the 1960s. An official
      conservation program was established in 1998 and now 12 different populations are
      currently maintained by a network of volunteer hobbyist breeders. Variation in
      the MHC-B region in these populations was examined using a panel of 90 selected
      SNP. A total of 195 samples from 12 distinct populations (average of 15
      individuals sampled per population) were genotyped with the 90 SNP panel specific
      for the MHC-B region, spanning 210,000 bp. There were 36 haplotypes found, 16 of
      which are a subset of 78 that had been previously identified in either
      commercially utilized or heritage breeds from North America with the remaining 20
      haplotypes being novel. The average number of MHC-B haplotypes found within each
      Finnish Landrace population was 5.9, and ranged from one to 13. While haplotypes
      common to multiple populations were found, population-specific haplotypes were
      also identified. This study shows that substantial MHC-B region diversity exists
      in the Finnish Landrace breed and exemplifies the significance tied to conserving
      multiple populations of rare breeds.

PMID- 28453653
TI  - The Bologna Annotation Resource (BAR 3.0): improving protein functional
      annotation.
AB  - BAR 3.0 updates our server BAR (Bologna Annotation Resource) for predicting
      protein structural and functional features from sequence. We increase data
      volume, query capabilities and information conveyed to the user. The core of BAR
      3.0 is a graph-based clustering procedure of UniProtKB sequences, following
      strict pairwise similarity criteria (sequence identity >=40% with alignment
      coverage >=90%). Each cluster contains the available annotation downloaded from
      UniProtKB, GO, PFAM and PDB. After statistical validation, GO terms and PFAM
      domains are cluster-specific and annotate new sequences entering the cluster
      after satisfying similarity constraints. BAR 3.0 includes 28 869 663 sequences in
      1 361 773 clusters, of which 22.2% (22 241 661 sequences) and 47.4% (24 555 055
      sequences) have at least one validated GO term and one PFAM domain, respectively.
      1.4% of the clusters (36% of all sequences) include PDB structures and the
      cluster is associated to a hidden Markov model that allows building template
      target alignment suitable for structural modeling. Some other 3 399 026 sequences
      are singletons. BAR 3.0 offers an improved search interface, allowing queries by
      UniProtKB-accession, Fasta sequence, GO-term, PFAM-domain, organism, PDB and
      ligand/s. When evaluated on the CAFA2 targets, BAR 3.0 largely outperforms our
      previous version and scores among state-of-the-art methods. BAR 3.0 is publicly
      available and accessible at http://bar.biocomp.unibo.it/bar3.

PMID- 28453654
TI  - Genomic Evidence that Methanotrophic Endosymbionts Likely Provide Deep-Sea
      Bathymodiolus Mussels with a Sterol Intermediate in Cholesterol Biosynthesis.
AB  - Sterols are key cyclic triterpenoid lipid components of eukaryotic cellular
      membranes, which are synthesized through complex multi-enzyme pathways. Similar
      to most animals, Bathymodiolus mussels, which inhabit deep-sea chemosynthetic
      ecosystems and harbor methanotrophic and/or thiotrophic bacterial endosymbionts,
      possess cholesterol as their main sterol. Based on the stable carbon isotope
      analyses, it has been suggested that host Bathymodiolus mussels synthesize
      cholesterol using a sterol intermediate derived from the methanotrophic
      endosymbionts. To test this hypothesis, we sequenced the genome of the
      methanotrophic endosymbiont in Bathymodiolus platifrons. The genome sequence data
      demonstrated that the endosymbiont potentially generates up to 4,4-dimethyl
      cholesta-8,14,24-trienol, a sterol intermediate in cholesterol biosynthesis, from
      methane. In addition, transcripts for a subset of the enzymes of the biosynthetic
      pathway to cholesterol downstream from a sterol intermediate derived from
      methanotroph endosymbionts were detected in our transcriptome data for B.
      platifrons. These findings suggest that this mussel can de novo synthesize
      cholesterol from methane in cooperation with the symbionts. By in situ
      hybridization analyses, we showed that genes associated with cholesterol
      biosynthesis from both host and endosymbionts were expressed exclusively in the
      gill epithelial bacteriocytes containing endosymbionts. Thus, cholesterol
      production is probably localized within these specialized cells of the gill.
      Considering that the host mussel cannot de novo synthesize cholesterol and
      depends largely on endosymbionts for nutrition, the capacity of endosymbionts to
      synthesize sterols may be important in establishing symbiont-host relationships
      in these chemosynthetic mussels.

PMID- 28453656
TI  - Generic Drugs-Changes in Cost and Challenges in Practice.

PMID- 28453655
TI  - Multiple "Old Ages": The Influence of Social Context on Women's Aging Anxiety.
AB  - Objectives: Dominant views of aging generate anxiety for many adults-especially
      women, who face greater disadvantages in later life compared with men. However,
      little is known about changes in these concerns over time and their variation
      across women. Employing a feminist perspective on age relations, our study
      examines three social contexts affecting women's aging anxiety-social location,
      health, and social relationships. Method: Using a sample of women (n = 905) from
      Midlife in the United States (1995-1996; 2004-2006), logistic regression models
      examine predictors of over-time patterns in three aging anxiety sources-declining
      attractiveness, declining health, and reproductive aging. Results: Women report
      more declining-health anxiety, and it remains more stable over time than do
      declining-attractiveness and reproductive aging anxiety-both of which tend to
      decrease with age. The effects of social context vary across anxiety sources;
      however, more favorable over-time patterns are often associated with more
      disadvantaged social locations (i.e., older ages, non-white, lower socioeconomic
      status)-but better health and social relationships. Discussion: Our study, the
      first to examine over-time patterns in aging anxiety, illustrates women's
      multiple "old ages"-a reality manifesting in not only objective conditions of
      later life but also perceptions of aging. It provides insight on social and
      cultural processes shaping aging perceptions.

PMID- 28453657
TI  - Comparative ileal digestibility of amino acids in 00-rapeseed meal and rapeseed
      meal fed to growing male broilers.
AB  - Rapeseed meal (RSM) is a commonly used protein source in poultry diet but its
      usage is limited due to antinutritional factors, the glucosinolates (GLS) and
      erucic acid. The 00-rapeseed meal (00-RSM) is the developed variety of rapeseed
      with reduced GLS and erucic acid content through genetic selection. The present
      study was conducted with the objective of comparing the standardized ileal
      digestibility (SID) of amino acids (AA) in 00-RSM and RSM when fed to growing
      broilers. Three samples of each ingredient were collected from different sources.
      Two hundred and fifty two day-old male broilers (Hubbard * Hubbard) were fed a
      corn-soybean meal based starter diet in crumble form from day 1 to 13. On day 14,
      all chicks were individually weighed and randomly distributed to 42 replicate
      pens (6 birds in each pen). Six test diets (2 ingredient * 3 samples) with
      approximately 20% crude protein were made in mash form in such a way that the 6
      test ingredients served as the sole source of AA in one diet. The endogenous AAs
      (EAA) were determined by feeding a nitrogen-free diet to six replicate pens. Each
      test diet was fed to six replicates of broiler chicks from 14 to 21 days of age.
      Results indicated that the SID of all AA differed (P < 0.001) among 00-RSM
      samples. Among RSM samples, the SID of AA varied for arginine, methionine (P <
      0.01), histidine, leucine, lysine, aspartic acid, and phenylalanine (P < 0.05). A
      greater (P < 0.05) SID of all AA except arginine, histidine, phenylalanine,
      cysteine, and glutamic acid was observed in 00-RSM compared with RSM. In
      conclusion, 00-RSM had greater SID of AA compared with RSM and it is
      nutritionally superior to RSM to be used in broiler diets.

PMID- 28453659
TI  - Uridine Diphosphate-Glucuronosyltransferase (UGT) 2B Subfamily Interspecies
      Differences in Carnivores.
AB  - UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic
      metabolizing enzymes that conjugate a wide range of chemicals. Previous studies
      showed that Felidae and Pinnipedia species have very low UGT activities toward
      some phenolic compounds because of the UGT1A6 pseudogene and small numbers of
      UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various
      endogenous (eg, estrogens, androgens, and bile acids) and exogenous compounds
      (opioids, non-steroidal anti-inflammatory drugs, and environmental pollutants).
      However UGT2B activity and genetic background are unknown in carnivore species.
      Therefore, this study was performed to elucidate the species differences of
      UGT2Bs. Using typical substrates for UGT2Bs, UGT activity was measured in vitro.
      In addition, UGT2B genetic features are analyzed in silico. Results of UGT
      activity measurement indicate marked species differences between dogs and other
      carnivores (cats, Northern fur seals, Steller sea lions, Harbor seals, and
      Caspian seals). Dogs have very high Vmax/Km toward estradiol (17-glucuronide),
      estrone, lorazepam, oxazepam, and temazepam. Conversely, cats and pinniped
      species (especially Caspian seals and Harbor seals) have very low activities
      toward these substrates. The results of genetic synteny analysis indicate that
      Felidae and pinniped species have very small numbers of UGT2B isozymes (one or
      none) compared with dogs, rodents, and humans. Furthermore, Felidae species have
      the same nonsense mutation in UGT2B, which suggests that Felidae UGT2B31-like is
      also a pseudogene in addition to UGT1A6. These findings of lower activity of
      UGT2B suggest that Felidae and some pinniped species have very low UGT activity
      toward a wide range of chemicals. These results are important for Felidae and
      Pinnipedia species that are frequently exposed to drugs and environmental
      pollutants.

PMID- 28453658
TI  - Androgen receptor agonists increase lean mass, improve cardiopulmonary functions
      and extend survival in preclinical models of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a neuromuscular disease that predominantly
      affects boys as a result of mutation(s) in the dystrophin gene. DMD is
      characterized by musculoskeletal and cardiopulmonary complications, resulting in
      shorter life-span. Boys afflicted by DMD typically exhibit symptoms within 3-5
      years of age and declining physical functions before attaining puberty. We
      hypothesized that rapidly deteriorating health of pre-pubertal boys with DMD
      could be due to diminished anabolic actions of androgens in muscle, and that
      intervention with an androgen receptor (AR) agonist will reverse musculoskeletal
      complications and extend survival. While castration of dystrophin and utrophin
      double mutant (mdx-dm) mice to mimic pre-pubertal nadir androgen condition
      resulted in premature death, maintenance of androgen levels extended the
      survival. Non-steroidal selective-AR modulator, GTx-026, which selectively builds
      muscle and bone was tested in X-linked muscular dystrophy mice (mdx). GTx-026
      significantly increased body weight, lean mass and grip strength by 60-80% over
      vehicle-treated mdx mice. While vehicle-treated castrated mdx mice exhibited
      cardiopulmonary impairment and fibrosis of heart and lungs, GTx-026 returned
      cardiopulmonary function and intensity of fibrosis to healthy control levels. GTx
      026 elicits its musculoskeletal effects through pathways that are distinct from
      dystrophin-regulated pathways, making AR agonists ideal candidates for
      combination approaches. While castration of mdx-dm mice resulted in weaker muscle
      and shorter survival, GTx-026 treatment increased the muscle mass, function and
      survival, indicating that androgens are important for extended survival. These
      preclinical results support the importance of androgens and the need for
      intervention with AR agonists to treat DMD-affected boys.

PMID- 28453660
TI  - EFFECT OF PATIENT SIZE, ANATOMICAL LOCATION AND MODULATION STRENGTH ON DOSE
      DELIVERED AND IMAGE-QUALITY ON CT EXAMINATION.
AB  - To study the effect of patient size, anatomical location and modulation strength
      (MS) on image-quality and delivered dose of CT scans acquired with automatic
      exposure-control system (AEC). Four anthropomorphic phantoms (three paediatric
      and one thin adult) were studied, and normal and obese adults were simulated by
      placing bolus plates around the adult phantom. Thorax and abdomen-pelvis CT were
      performed using an AEC system equipped with five possible MS. Modulated tube
      current (mAsmod) was compared to Reference mAs and image-noise was assessed.
      Effective-mAs were lower than Reference-mAs for all but the obese phantom.
      However, reversal points were estimated for an effective diameter of 27.8 cm in
      thorax and 26.9 cm in abdomen-pelvis scans, beyond which the patterns of MS were
      inversed. mAsmod were dependent on attenuation differences among distinct
      anatomical location. Finally, dose delivered was associated to the mAsmod and
      patient's size, with both affecting image-quality.

PMID- 28453661
TI  - Photoreceptor outer segment as a sink for membrane proteins: hypothesis and
      implications in retinal ciliopathies.
AB  - The photoreceptor outer segment (OS) is a unique modification of the primary
      cilium, specialized for light perception. Being homologous organelles, the
      primary cilium and the OS share common building blocks and molecular machinery to
      construct and maintain them. The OS, however, has several unique structural
      features that are not seen in primary cilia. Although these unique features of
      the OS have been well documented, their implications in protein localization have
      been under-appreciated. In this review, we compare the structural properties of
      the primary cilium and the OS, and propose a hypothesis that the OS can act as a
      sink for membrane proteins. We further discuss the implications of this
      hypothesis in polarized protein localization in photoreceptors and mechanisms of
      photoreceptor degeneration in retinal ciliopathies.

PMID- 28453662
TI  - mGluR5 Tunes NGF/TrkA Signaling to Orient Spiny Stellate Neuron Dendrites Toward
      Thalamocortical Axons During Whisker-Barrel Map Formation.
AB  - Neurons receive and integrate synaptic inputs at their dendrites, thus dendritic
      patterning shapes neural connectivity and behavior. Aberrant dendritogenesis is
      present in neurodevelopmental disorders such as Down's syndrome and autism.
      Abnormal glutamatergic signaling has been observed in these diseases, as has
      dysfunction of the metabotropic glutamate receptor 5 (mGluR5). Deleting mGluR5 in
      cortical glutamatergic neurons disrupted their coordinated dendritic outgrowth
      toward thalamocortical axons and perturbed somatosensory circuits. Here we show
      that mGluR5 loss-of-function disrupts dendritogenesis of cortical neurons by
      increasing mRNA levels of nerve growth factor (NGF) and fibroblast growth factor
      10 (FGF10), in part through calcium-permeable AMPA receptors (CP-AMPARs), as the
      whisker-barrel map is forming. Postnatal NGF and FGF10 expression in cortical
      layer IV spiny stellate neurons differentially impacted dendritic patterns.
      Remarkably, NGF-expressing neurons exhibited dendritic patterns resembling mGluR5
      knockout neurons: increased total dendritic length/complexity and reduced
      polarity. Furthermore, suppressing the kinase activity of TrkA, a major NGF
      receptor, prevents aberrant dendritic patterning in barrel cortex of mGluR5
      knockout neurons. These results reveal novel roles for NGF-TrkA signaling and CP
      AMPARs for proper dendritic development of cortical neurons. This is the first in
      vivo demonstration that cortical neuronal NGF expression modulates dendritic
      patterning during postnatal brain development.

PMID- 28453663
TI  - Rasmussen-Torvik et al. Respond to "The Perfect Measure of Diastolic
      Dysfunction".

PMID- 28453664
TI  - Glycogen Synthesis in Glycogenin 1-Deficient Patients: A Role for Glycogenin 2 in
      Muscle.
AB  - Context: Glycogen storage disease (GSD) type XV is a rare disease caused by
      mutations in the GYG1 gene that codes for the core molecule of muscle glycogen,
      glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1
      deficient patients, suggesting an alternative for glycogen buildup. A likely
      candidate is glycogenin 2, an isoform expressed in the liver and heart but not in
      healthy skeletal muscle. Objective: We wanted to investigate the formation of
      glycogen and changes in glycogen metabolism in patients with GSD type XV. Design,
      Setting, and Patients: Two patients with mutations in the GYG1 gene were
      investigated for histopathology, ultrastructure, and expression of proteins
      involved in glycogen synthesis and metabolism. Results: Apart from occurrence of
      polyglucosan (PG) bodies in few fibers, glycogen appeared normal in most cells,
      and the concentration was normal in patients with GSD type XV. We found that
      glycogenin 1 was absent, but glycogenin 2 was present in the patients, whereas
      the opposite was the case in healthy controls. Electron microscopy revealed that
      glycogen was present between and not inside myofibrils in type II fibers,
      compromising the ultrastructure of these fibers, and only type I fibers contained
      PG bodies. We also found significant changes to the expression levels of several
      enzymes directly involved in glycogen and glucose metabolism. Conclusions: To our
      knowledge, this is the first report demonstrating expression of glycogenin 2 in
      glycogenin 1-deficient patients, suggesting that glycogenin 2 rescues the
      formation of glycogen in patients with glycogenin 1 deficiency.

PMID- 28453665
TI  - Corrigendum: Budesonide Multimatrix Is Efficacious for Mesalamine-refractory,
      Mild to Moderate Ulcerative Colitis: A Randomised, Placebo-controlled Trial.

PMID- 28453666
TI  - Inequalities in rural communities: adapting national deprivation indices for
      rural settings.
AB  - Background: Deprivation indices have been widely used in healthcare research and
      planning in the United Kingdom. Existing indices, however, are dominated by
      characteristics of urban populations that may be less relevant in capturing the
      nature of rural deprivation. We explore if deprivation indices can be modified to
      make them more sensitive to displaying rural disadvantage in England. Methods:
      The analysis focussed on the 2011 Carstairs Index (Carstairs2011) and the 2010
      English Index of Multiple Deprivation (IMD2010). We removed all urban areas as
      identified by the Office for National Statistics Rural-Urban Area Classifications
      and mapped the Carstairs2011 and IMD2010 across the remaining rural areas using
      rural-specific quintiles. Results: Our method was effective in displaying much
      greater heterogeneity in rural areas than was apparent in the original indices.
      We received positive feedback from Directors of Public Health who confirmed that
      the observed patterns mirror their experiences and first-hand knowledge on the
      ground. Conclusions: Our maps of Carstairs2011 and IMD2010 for rural areas might
      strengthen the evidence base for rural planning and service provision. The
      modified deprivation indices, however, were not specifically formulated for rural
      populations and further work is needed to explore alternative input variables to
      produce a more rural-specific measure of deprivation.

PMID- 28453667
TI  - Linearity of network proximity measures: implications for set-based queries and
      significance testing.
AB  - Motivation: In recent years, various network proximity measures have been
      proposed to facilitate the use of biomolecular interaction data in a broad range
      of applications. These applications include functional annotation, disease gene
      prioritization, comparative analysis of biological systems and prediction of new
      interactions. In such applications, a major task is the scoring or ranking of the
      nodes in the network in terms of their proximity to a given set of 'seed' nodes
      (e.g. a group of proteins that are identified to be associated with a disease, or
      are deferentially expressed in a certain condition). Many different network
      proximity measures are utilized for this purpose, and these measures are quite
      diverse in terms of the benefits they offer. Results: We propose a unifying
      framework for characterizing network proximity measures for set-based queries. We
      observe that many existing measures are linear, in that the proximity of a node
      to a set of nodes can be represented as an aggregation of its proximity to the
      individual nodes in the set. Based on this observation, we propose methods for
      processing of set-based proximity queries that take advantage of sparse local
      proximity information. In addition, we provide an analytical framework for
      characterizing the distribution of proximity scores based on reference models
      that accurately capture the characteristics of the seed set (e.g. degree
      distribution and biological function). The resulting framework facilitates
      computation of exact figures for the statistical significance of network
      proximity scores, enabling assessment of the accuracy of Monte Carlo simulation
      based estimation methods. Availability and Implementation: Implementations of the
      methods in this paper are available at https://bioengine.case.edu/crosstalker
      which includes a robust visualization for results viewing. Contact: stm@case.edu
      or mxk331@case.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 28453668
TI  - A mass graph-based approach for the identification of modified proteoforms using
      top-down tandem mass spectra.
AB  - Motivation: Although proteomics has rapidly developed in the past decade,
      researchers are still in the early stage of exploring the world of complex
      proteoforms, which are protein products with various primary structure
      alterations resulting from gene mutations, alternative splicing, post
      translational modifications, and other biological processes. Proteoform
      identification is essential to mapping proteoforms to their biological functions
      as well as discovering novel proteoforms and new protein functions. Top-down mass
      spectrometry is the method of choice for identifying complex proteoforms because
      it provides a 'bird's eye view' of intact proteoforms. The combinatorial
      explosion of various alterations on a protein may result in billions of possible
      proteoforms, making proteoform identification a challenging computational
      problem. Results: We propose a new data structure, called the mass graph, for
      efficient representation of proteoforms and design mass graph alignment
      algorithms. We developed TopMG, a mass graph-based software tool for proteoform
      identification by top-down mass spectrometry. Experiments on top-down mass
      spectrometry datasets showed that TopMG outperformed existing methods in
      identifying complex proteoforms. Availability and implementation:
      http://proteomics.informatics.iupui.edu/software/topmg/. Contact:
      xwliu@iupui.edu. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 28453669
TI  - Image-based correction of continuous and discontinuous non-planar axial
      distortion in serial section microscopy.
AB  - Motivation: Serial section microscopy is an established method for detailed
      anatomy reconstruction of biological specimen. During the last decade, high
      resolution electron microscopy (EM) of serial sections has become the de-facto
      standard for reconstruction of neural connectivity at ever increasing scales (EM
      connectomics). In serial section microscopy, the axial dimension of the volume is
      sampled by physically removing thin sections from the embedded specimen and
      subsequently imaging either the block-face or the section series. This process
      has limited precision leading to inhomogeneous non-planar sampling of the axial
      dimension of the volume which, in turn, results in distorted image volumes. This
      includes that section series may be collected and imaged in unknown order.
      Results: We developed methods to identify and correct these distortions through
      image-based signal analysis without any additional physical apparatus or
      measurements. We demonstrate the efficacy of our methods in proof of principle
      experiments and application to real world problems. Availability and
      Implementation: We made our work available as libraries for the ImageJ
      distribution Fiji and for deployment in a high performance parallel computing
      environment. Our sources are open and available at
      http://github.com/saalfeldlab/section-sort, http://github.com/saalfeldlab/z
      spacing and http://github.com/saalfeldlab/z-spacing-spark. Contact:
      saalfelds@janelia.hhmi.org. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 28453670
TI  - GppFst: genomic posterior predictive simulations of FST and dXY for identifying
      outlier loci from population genomic data.
AB  - Summary: We introduce GppFst, an open source R package that generates posterior
      predictive distributions of FST and dx under a neutral coalescent model to
      identify putative targets of selection from genomic data. Availability and
      Implementation: GppFst is available at ( https://github.com/radamsRHA/GppFst ).
      Contact: todd.castoe@uta.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 28453671
TI  - Wright-Fisher exact solver (WFES): scalable analysis of population genetic models
      without simulation or diffusion theory.
AB  - Motivation: The simplifying assumptions that are used widely in theoretical
      population genetics may not always be appropriate for empirical population
      genetics. General computational approaches that do not require the assumptions of
      classical theory are therefore quite desirable. One such general approach is
      provided by the theory of absorbing Markov chains, which can be used to obtain
      exact results by directly analyzing population genetic Markov models, such as the
      classic bi-allelic Wright-Fisher model. Although these approaches are sometimes
      used, they are usually forgone in favor of simulation methods, due to the
      perception that they are too computationally burdensome. Here we show that,
      surprisingly, direct analysis of virtually any Markov chain model in population
      genetics can be made quite efficient by exploiting transition matrix sparsity and
      by solving restricted systems of linear equations, allowing a wide variety of
      exact calculations (within machine precision) to be easily and rapidly made on
      modern workstation computers. Results: We introduce Wright-Fisher Exact Solver
      (WFES), a fast and scalable method for direct analysis of Markov chain models in
      population genetics. WFES can rapidly solve for both long-term and transient
      behaviours including fixation and extinction probabilities, expected times to
      fixation or extinction, sojourn times, expected allele age and variance, and
      others. Our implementation requires only seconds to minutes of runtime on modern
      workstations and scales to biological population sizes ranging from humans to
      model organisms. Availability and Implementation: The code is available at
      https://github.com/dekoning-lab/wfes. Contact: jason.dekoning@ucalgary.ca.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28453672
TI  - Primerize-2D: automated primer design for RNA multidimensional chemical mapping.
AB  - Summary: Rapid RNA synthesis of comprehensive single mutant libraries and
      targeted multiple mutant libraries is enabling new multidimensional chemical
      approaches to solve RNA structures. PCR assembly of DNA templates and in vitro
      transcription allow synthesis and purification of hundreds of RNA mutants in a
      cost-effective manner, with sharing of primers across constructs allowing
      significant reductions in expense. However, these protocols require organization
      of primer locations across numerous 96 well plates and guidance for pipetting,
      non-trivial tasks for which informatics and visualization tools can prevent
      costly errors. We report here an online tool to accelerate synthesis of large
      libraries of desired mutants through design and efficient organization of
      primers. The underlying program and graphical interface have been experimentally
      tested in our laboratory for RNA domains with lengths up to 300 nucleotides and
      libraries encompassing up to 960 variants. In addition to the freely available
      Primerize-2D server, the primer design code is available as a stand-alone Python
      package for broader applications. Availability and Implementation:
      http://primerize2d.stanford.edu. Contact: rhiju@stanford.edu. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28453673
TI  - VEXOR: an integrative environment for prioritization of functional variants in
      fine-mapping analysis.
AB  - Motivation: The identification of the functional variants responsible for
      observed genome-wide association studies (GWAS) signals is one of the most
      challenging tasks of the post-GWAS research era. Several tools have been
      developed to annotate genetic variants by their genomic location and potential
      functional implications. Each of these tools has its own requirements and
      internal logic, which forces the user to become acquainted with each interface.
      Results: From an awareness of the amount of work needed to analyze a single
      locus, we have built a flexible, versatile and easy-to-use web interface designed
      to help in prioritizing variants and predicting their potential functional
      implications. This interface acts as a single-point of entry linking association
      results with reference tools and relevant experiments. Availability and
      Implementation: VEXOR is an integrative web application implemented through the
      Shiny framework and available at: http://romix.genome.ulaval.ca/vexor. Contact:
      arnaud.droit@crchuq.ulaval.ca. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 28453674
TI  - ntCard: a streaming algorithm for cardinality estimation in genomics data.
AB  - Motivation: Many bioinformatics algorithms are designed for the analysis of
      sequences of some uniform length, conventionally referred to as k -mers. These
      include de Bruijn graph assembly methods and sequence alignment tools. An
      efficient algorithm to enumerate the number of unique k -mers, or even better, to
      build a histogram of k -mer frequencies would be desirable for these tools and
      their downstream analysis pipelines. Among other applications, estimated
      frequencies can be used to predict genome sizes, measure sequencing error rates,
      and tune runtime parameters for analysis tools. However, calculating a k -mer
      histogram from large volumes of sequencing data is a challenging task. Results:
      Here, we present ntCard, a streaming algorithm for estimating the frequencies of
      k -mers in genomics datasets. At its core, ntCard uses the ntHash algorithm to
      efficiently compute hash values for streamed sequences. It then samples the
      calculated hash values to build a reduced representation multiplicity table
      describing the sample distribution. Finally, it uses a statistical model to
      reconstruct the population distribution from the sample distribution. We have
      compared the performance of ntCard and other cardinality estimation algorithms.
      We used three datasets of 480 GB, 500 GB and 2.4 TB in size, where the first two
      representing whole genome shotgun sequencing experiments on the human genome and
      the last one on the white spruce genome. Results show ntCard estimates k -mer
      coverage frequencies >15* faster than the state-of-the-art algorithms, using
      similar amount of memory, and with higher accuracy rates. Thus, our benchmarks
      demonstrate ntCard as a potentially enabling technology for large-scale genomics
      applications. Availability and Implementation: ntCard is written in C ++ and is
      released under the GPL license. It is freely available at
      https://github.com/bcgsc/ntCard. Contact: hmohamadi@bcgsc.ca or ibirol@bcgsc.ca.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28453675
TI  - CircosVCF: circos visualization of whole-genome sequence variations stored in VCF
      files.
AB  - Summary: Visualization of whole-genomic variations in a meaningful manner assists
      researchers in gaining new insights into the underlying data, especially when it
      comes in the context of whole genome comparisons. CircosVCF is a web based
      visualization tool for genome-wide variant data described in VCF files, using
      circos plots. The user friendly interface of CircosVCF supports an interactive
      design of the circles in the plot, and the integration of additional information
      such as experimental data or annotations. The provided visualization capabilities
      give a broad overview of the genomic relationships between genomes, and allow
      identification of specific meaningful SNPs regions. Availability and
      Implementation: CircosVCF was implemented in JavaScript and is available at
      http://www.ariel.ac.il/research/fbl/software. Contact: malisa@ariel.ac.il.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28453676
TI  - fastMitoCalc: an ultra-fast program to estimate mitochondrial DNA copy number
      from whole-genome sequences.
AB  - Availability and Implementation: fastMitoCalc is available at
      https://lgsun.irp.nia.nih.gov/hsgu/software/mitoAnalyzer/index.html. Contact:
      jun.ding@nih.gov. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 28453677
TI  - AFS: identification and quantification of species composition by metagenomic
      sequencing.
AB  - Summary: DNA-based methods to detect and quantify taxon composition in biological
      materials are often based on species-specific polymerase chain reaction, limited
      to detecting species targeted by the assay. Next-generation sequencing overcomes
      this drawback by untargeted shotgun sequencing of whole metagenomes at affordable
      cost. Here we present AFS, a software pipeline for quantification of species
      composition in food. AFS uses metagenomic shotgun sequencing and sequence read
      counting to infer species proportions. Using Illumina data from a reference
      sausage comprising four species, we reveal that AFS is independent of the
      sequencing assay and library preparation protocol. Cost-saving short (50-bp)
      single-end reads and Nextera (r) library preparation yield reliable results.
      Availability and Implementation: Datasets, binaries and usage instructions are
      available under http://all-food-seq.sourceforge.net. Raw data is available at
      NCBI's SRA with accession number PRJNA271645. Contact: hankeln@uni-mainz.de.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28453678
TI  - Chainy: an universal tool for standardized relative quantification in real-time
      PCR.
AB  - Summary: Chainy is a cross-platform web tool providing systematic pipelines and
      steady criteria to process real-time PCR data, including the calculation of
      efficiencies from raw data by kinetic methods, evaluation of the suitability of
      multiple references, standardized normalization using one or more references, and
      group-wise relative quantification statistical testing. We illustrate the utility
      of Chainy for differential expression and chromatin immunoprecipitation
      enrichment (ChIP-QPCR) analysis. Availability and Implementation: Chainy is open
      source and freely available at http://maplab.cat/chainy. Contact:
      imallona@igtp.cat. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 28453679
TI  - BioPAXViz: a cytoscape application for the visual exploration of metabolic
      pathway evolution.
AB  - Summary: BioPAXViz is a Cytoscape (version 3) application, providing a
      comprehensive framework for metabolic pathway visualization. Beyond the basic
      parsing, viewing and browsing roles, the main novel function that BioPAXViz
      provides is a visual comparative analysis of metabolic pathway topologies across
      pre-computed pathway phylogenomic profiles given a species phylogeny.
      Furthermore, BioPAXViz supports the display of hierarchical trees that allow
      efficient navigation through sets of variants of a single reference pathway.
      Thus, BioPAXViz can significantly facilitate, and contribute to, the study of
      metabolic pathway evolution and engineering. Availability and Implementation:
      BioPAXViz has been developed as a Cytoscape app and is available at:
      https://github.com/CGU-CERTH/BioPAX.Viz. The software is distributed under the
      MIT License and is accompanied by example files and data. Additional
      documentation is available at the aforementioned GitHub repository. Contact:
      ouzounis@certh.gr.

PMID- 28453680
TI  - The genetic map comparator: a user-friendly application to display and compare
      genetic maps.
AB  - Motivation: Marker-assisted selection strongly relies on genetic maps to
      accelerate breeding programs. High-density maps are now available for numerous
      species. Dedicated tools are required to compare several high-density maps on the
      basis of their key characteristics, while pinpointing their differences and
      similarities. Results: We developed the Genetic Map Comparator-a web-based
      application for easy comparison of different maps according to their key
      statistics and the relative positions of common markers. Availability and
      Implementation: The Genetic Map Comparator is available online at:
      http://bioweb.supagro.inra.fr/geneticMapComparator. The source code is freely
      available on GitHub under the under the CeCILL general public license:
      https://github.com/holtzy/GenMap-Comparator. Contact: Holtz@supagro.fr;
      Ranwez@supagro.fr.

PMID- 28453682
TI  - DistributedFBA.jl: high-level, high-performance flux balance analysis in Julia.
AB  - Motivation: Flux balance analysis and its variants are widely used methods for
      predicting steady-state reaction rates in biochemical reaction networks. The
      exploration of high dimensional networks with such methods is currently hampered
      by software performance limitations. Results: DistributedFBA.jl is a high-level,
      high-performance, open-source implementation of flux balance analysis in Julia.
      It is tailored to solve multiple flux balance analyses on a subset or all the
      reactions of large and huge-scale networks, on any number of threads or nodes.
      Availability and Implementation: The code is freely available on
      github.com/opencobra/COBRA.jl. The documentation can be found at
      opencobra.github.io/COBRA.jl. Contact: ronan.mt.fleming@gmail.com. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28453681
TI  - Sphinx: merging knowledge-based and ab initio approaches to improve protein loop
      prediction.
AB  - Motivation: Loops are often vital for protein function, however, their irregular
      structures make them difficult to model accurately. Current loop modelling
      algorithms can mostly be divided into two categories: knowledge-based, where
      databases of fragments are searched to find suitable conformations and ab initio,
      where conformations are generated computationally. Existing knowledge-based
      methods only use fragments that are the same length as the target, even though
      loops of slightly different lengths may adopt similar conformations. Here, we
      present a novel method, Sphinx, which combines ab initio techniques with the
      potential extra structural information contained within loops of a different
      length to improve structure prediction. Results: We show that Sphinx is able to
      generate high-accuracy predictions and decoy sets enriched with near-native loop
      conformations, performing better than the ab initio algorithm on which it is
      based. In addition, it is able to provide predictions for every target, unlike
      some knowledge-based methods. Sphinx can be used successfully for the difficult
      problem of antibody H3 prediction, outperforming RosettaAntibody, one of the
      leading H3-specific ab initio methods, both in accuracy and speed. Availability
      and Implementation: Sphinx is available at
      http://opig.stats.ox.ac.uk/webapps/sphinx. Contact: deane@stats.ox.ac.uk.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28453683
TI  - MobiDB-lite: fast and highly specific consensus prediction of intrinsic disorder
      in proteins.
AB  - Motivation: Intrinsic disorder (ID) is established as an important feature of
      protein sequences. Its use in proteome annotation is however hampered by the
      availability of many methods with similar performance at the single residue
      level, which have mostly not been optimized to predict long ID regions of size
      comparable to domains. Results: Here, we have focused on providing a single
      consensus-based prediction, MobiDB-lite, optimized for highly specific (i.e. few
      false positive) predictions of long disorder. The method uses eight different
      predictors to derive a consensus which is then filtered for spurious short
      predictions. Consensus prediction is shown to outperform the single methods when
      annotating long ID regions. MobiDB-lite can be useful in large-scale annotation
      scenarios and has indeed already been integrated in the MobiDB, DisProt and
      InterPro databases. Availability and Implementation: MobiDB-lite is available as
      part of the MobiDB database from URL: http://mobidb.bio.unipd.it/. An executable
      can be downloaded from URL: http://protein.bio.unipd.it/mobidblite/. Contact:
      silvio.tosatto@unipd.it. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 28453684
TI  - MAPPI-DAT: data management and analysis for protein-protein interaction data from
      the high-throughput MAPPIT cell microarray platform.
AB  - Summary: Protein-protein interaction (PPI) studies have dramatically expanded our
      knowledge about cellular behaviour and development in different conditions. A
      multitude of high-throughput PPI techniques have been developed to achieve
      proteome-scale coverage for PPI studies, including the microarray based Mammalian
      Protein-Protein Interaction Trap (MAPPIT) system. Because such high-throughput
      techniques typically report thousands of interactions, managing and analysing the
      large amounts of acquired data is a challenge. We have therefore built the MAPPIT
      cell microArray Protein Protein Interaction-Data management & Analysis Tool
      (MAPPI-DAT) as an automated data management and analysis tool for MAPPIT cell
      microarray experiments. MAPPI-DAT stores the experimental data and metadata in a
      systematic and structured way, automates data analysis and interpretation, and
      enables the meta-analysis of MAPPIT cell microarray data across all stored
      experiments. Availability and Implementation: MAPPI-DAT is developed in Python,
      using R for data analysis and MySQL as data management system. MAPPI-DAT is cross
      platform and can be ran on Microsoft Windows, Linux and OS X/macOS. The source
      code and a Microsoft Windows executable are freely available under the permissive
      Apache2 open source license at https://github.com/compomics/MAPPI-DAT. Contact:
      jan.tavernier@vib-ugent.be or lennart.martens@vib-ugent.be. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 28453685
TI  - PhenoCurve: capturing dynamic phenotype-environment relationships using phenomics
      data.
AB  - Motivation: Phenomics is essential for understanding the mechanisms that regulate
      or influence growth, fitness, and development. Techniques have been developed to
      conduct high-throughput large-scale phenotyping on animals, plants and humans,
      aiming to bridge the gap between genomics, gene functions and traits. Although
      new developments in phenotyping techniques are exciting, we are limited by the
      tools to analyze fully the massive phenotype data, especially the dynamic
      relationships between phenotypes and environments. Results: We present a new
      algorithm called PhenoCurve, a knowledge-based curve fitting algorithm, aiming to
      identify the complex relationships between phenotypes and environments, thus
      studying both values and trends of phenomics data. The results on both real and
      simulated data showed that PhenoCurve has the best performance among all the six
      tested methods. Its application to photosynthesis hysteresis pattern
      identification reveals new functions of core genes that control photosynthetic
      efficiency in response to varying environmental conditions, which are critical
      for understanding plant energy storage and improving crop productivity.
      Availability and Implementation: Software is available at
      phenomics.uky.edu/PhenoCurve. Contact: chen.jin@uky.edu or kramerd8@cns.msu.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 28453686
TI  - The null hypothesis of GSEA, and a novel statistical model for competitive gene
      set analysis.
AB  - Motivation: Competitive gene set analysis intends to assess whether a specific
      set of genes is more associated with a trait than the remaining genes. However,
      the statistical models assumed to date to underly these methods do not enable a
      clear cut formulation of the competitive null hypothesis. This is a major
      handicap to the interpretation of results obtained from a gene set analysis.
      Results: This work presents a hierarchical statistical model based on the notion
      of dependence measures, which overcomes this problem. The two levels of the model
      naturally reflect the modular structure of many gene set analysis methods. We
      apply the model to show that the popular GSEA method, which recently has been
      claimed to test the self-contained null hypothesis, actually tests the
      competitive null if the weight parameter is zero. However, for this result to
      hold strictly, the choice of the dependence measures underlying GSEA and the
      estimators used for it is crucial. Contact: bdebrabant@health.sdu.dk.
      Supplementary information: Supplementary material is available at Bioinformatics
      online.

PMID- 28453687
TI  - GDISC: a web portal for integrative analysis of gene-drug interaction for
      survival in cancer.
AB  - Summary: Survival analysis has been applied to The Cancer Genome Atlas (TCGA)
      data. Although drug exposure records are available in TCGA, existing survival
      analyses typically did not consider drug exposure, partly due to naming
      inconsistencies in the data. We have spent extensive effort to standardize the
      drug exposure data, which enabled us to perform survival analysis on drug
      stratified subpopulations of cancer patients. Using this strategy, we integrated
      gene copy number data, drug exposure data and patient survival data to infer gene
      drug interactions that impact survival. The collection of all analyzed gene-drug
      interactions in 32 cancer types are organized and presented in a searchable web
      portal called gene-drug Interaction for survival in cancer (GDISC). GDISC allows
      biologists and clinicians to interactively explore the gene-drug interactions
      identified in the context of TCGA, and discover interactions associated to their
      favorite cancer, drug and/or gene of interest. In addition, GDISC provides the
      standardized drug exposure data, which is a valuable resource for developing new
      methods for drug-specific analysis. Availability and Implementation: GDISC is
      available at https://gdisc.bme.gatech.edu/. Contact: peng.qiu@bme.gatech.edu.

PMID- 28453688
TI  - Edlib: a C/C ++ library for fast, exact sequence alignment using edit distance.
AB  - Summary: We present Edlib, an open-source C/C ++ library for exact pairwise
      sequence alignment using edit distance. We compare Edlib to other libraries and
      show that it is the fastest while not lacking in functionality and can also
      easily handle very large sequences. Being easy to use, flexible, fast and low on
      memory usage, we expect it to be easily adopted as a building block for future
      bioinformatics tools. Availability and Implementation: Source code, installation
      instructions and test data are freely available for download at
      https://github.com/Martinsos/edlib, under the MIT licence. Edlib is implemented
      in C/C ++ and supported on Linux, MS Windows, and Mac OS. Contact:
      mile.sikic@fer.hr. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 28453689
TI  - Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis.
AB  - Background: Periodontal disease (PD), now our commonest infectious disorder leads
      to tooth loss, and has been linked to various systemic diseases, including
      various types of cancer. The aim of this study is to provide a systematic review
      and a meta-analysis of the relationship between PD, edentulism, and pancreatic
      cancer (PC). Patients and methods: From an initial review of 327 references we
      selected eight studies concerning periodontitis or edentulism with sufficient
      quantitative information to allow us to examine the risk of PC. We used relative
      risks (RRs), hazard ratios, or odds ratios to measure the association between
      periodontitis, edentulism, and PC. We employed random effects models to obtain
      summary risks, and we also provide measures of study differences and possible
      biases. Results: The summary RR for periodontitis and PC was 1.74 [95% confidence
      interval (CI) 1.41-2.15] and 1.54 for edentulism (95% CI 1.16-2.05). There was no
      evidence of heterogeneity for either variable, and no evidence of publication
      bias. The studies included reports from three continents, suggesting that the
      association is generalizable. Most of the studies were adjusted for variables
      thought to be associated with PC, such as gender, smoking, BMI, diabetes, and
      alcohol. Conclusions: Using meta-analysis, both periodontitis and edentulism
      appear to be associated with PC, even after adjusting for common risk factors. As
      yet, the mechanisms linking oral disease and PC are uncertain, but could be
      related to changes in the oral microbiome-an area of current research.

PMID- 28453690
TI  - Subgroups and prognostication in stage III colon cancer: future perspectives for
      adjuvant therapy.
AB  - Since the MOSAIC study, oxaliplatin-based adjuvant chemotherapy has been the
      standard treatment of stage III colon cancer. Combination therapy with
      fluoropyrimidines and oxaliplatin has improved overall survival (OS) and reduced
      the risk of recurrence in patients with resected stage III colon cancer. However,
      only 20% of patients really benefit from adjuvant chemotherapy, exposing 80% of
      patients to unnecessary toxicity. Recent analyses of large multicenter adjuvant
      studies have focused on the prognostication of OS and disease-free survival in
      stage III colon cancer in order to reduce over-treatment and to find more
      accurate prognostic tools than those used for adjuvant treatment decision-making
      in stage II disease. Indeed, clinical and pathological prognostic factors,
      although important, are not sufficient to decide which stage III patients will
      benefit from adjuvant therapy, and biomarkers will help select patient that need
      adjuvant treatment. Molecular markers such as microsatellite status and BRAF and
      KRAS mutations have recently been explored, and molecular signatures have been
      identified as promising prognostic factor for OS. Furthermore, recent studies
      have highlighted the prognostic value of immune infiltration. This review focuses
      on pathologic, immunologic and molecular prognostic markers for stage III colon
      cancer that could help clinicians tailor adjuvant treatment in a comprehensive
      transversal approach.

PMID- 28453691
TI  - High-risk human papillomavirus in anal squamous cell carcinoma: a 'conservative'
      leading role.

PMID- 28453692
TI  - Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients
      with recurrent carcinoma of the anal canal.
AB  - Background: Safety and efficacy of pembrolizumab, a humanized programmed death 1
      monoclonal antibody, was assessed in KEYNOTE-028, a multicohort, phase Ib trial
      for patients with programmed death ligand 1 (PD-L1)-positive advanced solid
      tumors. We report results for the cohort of patients with advanced anal
      carcinoma. Patients and methods: Patients with PD-L1-positive tumors (>=1%)
      received intravenous pembrolizumab 10 mg/kg once every 2 weeks for up to 2 years
      or until confirmed progression or unacceptable toxicity. Response was assessed
      every 8 weeks for the first 6 months and every 12 weeks thereafter per Response
      Evaluation Criteria In Solid Tumors, version 1.1. Primary endpoints were safety
      and overall response rate per investigator review. Secondary endpoints included
      progression-free survival, overall survival, and response duration. Data cutoff
      date was 1 July 2015. Results: Of the 43 patients with advanced anal carcinoma
      evaluable for PD-L1 expression, 32 (74%) had PD-L1-positive tumors as assessed
      with the 22C3 prototype assay, of whom 25 were enrolled between April and
      September 2014. Sixteen patients (64%) experienced treatment-related adverse
      events; the most common ones were diarrhea and fatigue in four patients (16%)
      each and nausea in three patients (12%). There were no treatment-related deaths
      or discontinuations as of the data cutoff date. Among the 24 patients with
      squamous cell carcinoma histology, four had confirmed partial response, for an
      overall response rate of 17% [95% confidence interval (CI), 5%-37%) and 10 (42%)
      had confirmed stable disease, for a disease control rate of 58%. One additional
      patient with non-squamous histology had confirmed stable disease. Conclusion: In
      this population of patients with PD-L1-positive advanced squamous cell anal
      carcinoma, pembrolizumab demonstrated a manageable safety profile and encouraging
      antitumor activity. These data support further study of pembrolizumab for this
      patient population. ClinicalTrials.gov: NCT02054806.

PMID- 28453693
TI  - Racial disparities in prostate cancer outcome among prostate-specific antigen
      screening eligible populations in the United States.
AB  - Background: In 2012, the United States Preventive Services Task Force (USPSTF)
      recommended against prostate-specific antigen (PSA) screening, despite evidence
      that Black men are at a higher risk of prostate cancer-specific mortality (PCSM).
      We evaluated whether Black men of potentially screening-eligible age (55-69
      years) are at a disproportionally high risk of poor outcomes. Patients and
      methods: The SEER database was used to study 390 259 men diagnosed with prostate
      cancer in the United States between 2004 and 2011. Multivariable logistic
      regression modeled the association between Black race and stage of presentation,
      while Fine-Gray competing risks regression modeled the association between Black
      race and PCSM, both as a function of screening eligibility (age 55-69 years
      versus not). Results: Black men were more likely to present with metastatic
      disease (adjusted odds ratio [AOR] 1.65; 1.58-1.72; P < 0.001) and were at a
      higher risk of PCSM (adjusted hazard ratio [AHR] 1.36; 1.27-1.46; P < 0.001)
      compared to non-Black men. There were significant interactions between race and
      PSA-screening eligibility such that Black patients experienced more
      disproportionate rates of metastatic disease (AOR 1.76; 1.65-1.87 versus 1.55;
      1.47-1.65; Pinteraction < 0.001) and PCSM (AHR 1.53; 1.37-1.70 versus 1.25; 1.14
      1.37; Pinteraction = 0.01) in the potentially PSA-screening eligible group than
      in the group not eligible for screening. Conclusions: Racial disparities in
      prostate cancer outcome among Black men are significantly worse in PSA-screening
      eligible populations. These results raise the possibility that Black men could be
      disproportionately impacted by recommendations to end PSA screening in the United
      States and suggest that Black race should be included in the updated USPSTF PSA
      screening guidelines.

PMID- 28453694
TI  - Clinical benefit, price and approval characteristics of FDA-approved new drugs
      for treating advanced solid cancer, 2000-2015.
AB  - Background: Prices of anti-cancer drugs are skyrocking. We aimed to assess the
      clinical benefit of new drugs for treating advanced solid tumors at the time of
      their approval by the US Food and Drug Administration (FDA) and to search for a
      relation between price and clinical benefit of drugs. Materials and methods: We
      included all new molecular entities and new biologics for treating advanced solid
      cancer that were approved by the FDA between 2000 and 2015. The clinical benefit
      of drugs was graded based on FDA medical review of pivotal clinical trials using
      the 2016-updated of the American Society of Clinical Oncology Value Framework
      (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical
      Benefit Scale (ESMO-MCBS). Characteristics of drugs and approvals were obtained
      from publicly available FDA documents and price was evaluated according to US
      Medicare, US Veterans Health Administration and United Kingdom market systems.
      Results: The FDA approved 51 new drugs for advanced solid cancer from 2000 to
      2015; we could evaluate the value of 37 drugs (73%). By the ESMO-MCBS, five drugs
      (14%) were grade one (the lowest), nine (24%) grade two, 10 (27%) grade three, 11
      (30%) grade four and two (5%) grade five (the highest). Thus, 13 drugs (35%)
      showed a meaningful clinical benefit (scale levels 4 and 5). By the ASCO-VF which
      had a range of 3.4-67, the median drug value was 37 (interquartile range 20-52).
      We found no relationship between clinical benefit and drug price (P = 0.9). No
      characteristic of drugs and of approval was significantly associated with
      clinical benefit. Conclusion: Many recently FDA-approved new cancer drugs did not
      have high clinical benefit as measured by current scales. We found no relation
      between the price of drugs and benefit to society and patients.

PMID- 28453695
TI  - Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in
      patients with refractory metastatic colorectal cancer.
AB  - Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS
      102's main anti-tumor action. We tested whether genetic polymorphisms in
      homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is
      associated with outcomes in refractory metastatic colorectal cancer (mCRC)
      patients treated with TAS-102. Patients and methods: We analyzed genomic DNA
      extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients
      receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a
      control cohort of 52 patients receiving regorafenib. Single nucleotide
      polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX,
      RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1,
      PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate
      analysis for the evaluation cohort, patients with any G allele in ATM rs609429
      had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4
      months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in
      XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs.
      2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months,
      HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In
      multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In
      the validation cohort, patients having ATM rs609429 with any G allele showed
      longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though
      without statistical significance. Conclusion: Genetic variants in the HR pathway
      may predict clinical outcome in mCRC patients receiving TAS-102.

PMID- 28453696
TI  - Epstein-Barr virus-associated gastric cancer reveals intratumoral heterogeneity
      of PIK3CA mutations.
AB  - Background: Recent whole-genome sequencing identified four molecular subtypes of
      gastric cancer (GC), of which the subgroup of Epstein-Barr virus-associated GC
      (EBVaGC) showed a significant enrichment of PIK3CA mutations. We here aimed to
      validate independently the enrichment of PIK3CA mutations in EBVaGC of a Central
      European GC cohort, to correlate EBV status with clinico-pathological patient
      characteristics and to test for a major issue of GC, intratumoral heterogeneity.
      Patients and methods: In a first step, 484 GCs were screened for EBV and PIK3CA
      hot spot mutations of exon 9/20 using EBER in situ hybridization and
      pyrosequencing, respectively. Secondly, an extended sequencing of PIK3CA also
      utilizing next generation sequencing was carried out in all EBVaGCs and 96
      corresponding lymph node metastases. Results: Twenty-two GCs were EBER-positive,
      all being of latency type I. Intratumoral heterogeneity of EBER-positivity was
      found in 18% of EBVaGCs. Twenty-three GCs held PIK3CA mutations in hot spot
      regions of exon 9 or 20, being significantly more common in EBVaGCs (P < 0.001).
      Subsequent extended sequencing of PIK3CA of EBVaGCs showed that 14% harvested
      three to five different PIK3CA genotypes (including wildtype) in the same primary
      tumor, albeit in histologically and spatially distinct tumor areas, and that
      intratumoral heterogeneity of PIK3CA was also present in the corresponding lymph
      node metastases. Conclusions: Our findings unravel issues of tumor heterogeneity
      and illustrate that the assessment of the EBV status in tissue biopsies might
      carry the risk of sampling errors, which may significantly hamper adequate
      molecular tumor classification in a more clinical setting. Moreover, this is the
      first report of intratumoral heterogeneity of PIK3CA mutations in GC, and our
      findings lead to the conclusion that PIK3CA mutant and -wildtype tumor subclones
      are skilled to metastasize independently to different regional lymph nodes.

PMID- 28453698
TI  - Reply to 'Higher rate of severe toxicities in obese patients receiving dose-dense
      (dd) chemotherapy according to unadjusted body surface area: results of the
      prospectively randomized GAIN study' by J. Furlanetto et al.

PMID- 28453697
TI  - Prediction of overall survival in stage II and III colon cancer beyond TNM
      system: a retrospective, pooled biomarker study.
AB  - Background: TNM staging alone does not accurately predict outcome in colon cancer
      (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to
      what extent the molecular markers microsatellite instability (MSI) and mutations
      in BRAF or KRAS improve prognostic estimation in multivariable models that
      include detailed clinicopathological annotation. Patients and methods: After
      imputation of missing at random data, a subset of patients accrued in phase 3
      trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3
      (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year
      overall survival that were subsequently validated internally in the remaining
      clinical trial samples (n = 1499), and also externally in different population
      cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients,
      and an additional series without treatment annotation (n = 782). Results: TNM
      staging, MSI and BRAFV600E mutation status remained independent prognostic
      factors in multivariable models across clinical trials cohorts and observational
      studies. Concordance indices increased from 0.61-0.68 in the TNM alone model to
      0.63-0.71 in models with added molecular markers, 0.65-0.73 with
      clinicopathological features and 0.66-0.74 with all covariates. In validation
      cohorts with complete annotation, the integrated time-dependent AUC rose from
      0.64 for the TNM alone model to 0.67 for models that included clinicopathological
      features, with or without molecular markers. In patient cohorts that received
      adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM,
      clinicopathological features and molecular markers was on an average 65%, 25% and
      10%, respectively. Conclusions: Incorporation of MSI, BRAFV600E and KRAS mutation
      status to overall survival models with TNM staging improves the ability to
      precisely prognosticate in stage II and III CC patients, but only modestly
      increases prediction accuracy in multivariable models that include
      clinicopathological features, particularly in chemotherapy-treated patients.

PMID- 28453699
TI  - MicroRNA-related genetic variants in iron regulatory genes, dietary iron intake,
      microRNAs and lung cancer risk.
AB  - Background: Genetic variations in MicroRNA (miRNA) binding sites may alter
      structural accessibility of miRNA binding sites to modulate risk of cancer. This
      large-scale integrative multistage study was aimed to evaluate the interplay of
      genetic variations in miRNA binding sites of iron regulatory pathway, dietary
      iron intake and lung cancer (LC) risk. Patients and methods: The interplay of
      genetic variant, dietary iron intake and LC risk was assessed in large-scale case
      control study. Functional characterization of the validated SNP and analysis of
      target miRNAs were performed. Results: We found that the miRNA binding site SNP
      rs1062980 in 3' UTR of Iron-Responsive Element Binding protein 2 gene (IREB2) was
      associated with a 14% reduced LC risk (P value = 4.9*10 - 9). Comparing to AA
      genotype, GG genotype was associated with a 27% reduced LC risk. This association
      was evident in males and ever-smokers but not in females and never-smokers.
      Higher level of dietary iron intake was significantly associated with 39% reduced
      LC risk (P value = 2.0*10 - 8). This association was only present in individuals
      with AG + AA genotypes with a 46% reduced risk (P value = 1.0*10 - 10), but not
      in GG genotype. The eQTL-analysis showed that rs1062980 significantly alters
      IREB2 expression level. Rs1062980 is predicted to alter a miR-29 binding site on
      IREB2 and indeed the expression of miR-29 is inversely correlated with IREB2
      expression. Further, we found that higher circulating miR-29a level was
      significantly associated with 78% increased LC risk. Conclusion: The miRNA
      binding site SNP rs1062980 in iron regulatory pathway, which may alter the
      expression of IREB2 potentially through modulating the binding of miR-29a,
      together with dietary iron intake may modify risk of LC both individually and
      jointly. These discoveries reveal novel pathway for understanding lung cancer
      tumorigenesis and risk stratification.

PMID- 28453700
TI  - A need to simplify informed consent documents in cancer clinical trials. A
      position paper of the ARCAD Group.
AB  - Background: In respect of the principle of autonomy and the right of self
      determination, obtaining an informed consent of potential participants before
      their inclusion in a study is a fundamental ethical obligation. The variations in
      national laws, regulations, and cultures contribute to complex informed consent
      documents for patients participating in clinical trials. Currently, only few
      ethics committees seem willing to address the complexity and the length of these
      documents and to request investigators and sponsors to revise them in a way to
      make them understandable for potential participants. The purpose of this work is
      to focus on the written information in the informed consent documentation for
      drug development clinical trials and suggests (i) to distinguish between
      necessary and not essential information, (ii) to define the optimal format
      allowing the best legibility of those documents. Methods: The Aide et Recherche
      en Cancerologie Digestive (ARCAD) Group, an international scientific committee
      involving oncologists from all over the world, addressed these issues and
      developed and uniformly accepted a simplified informed consent documentation for
      future clinical research. Results: A simplified form of informed consent with the
      leading part of 1200-1800 words containing all of the key information necessary
      to meet ethical and regulatory requirements and 'relevant supportive information
      appendix' of 2000-3000 words is provided. Conclusions: This position paper, on
      the basis of the ARCAD Group experts discussions, proposes our informed consent
      model and the rationale for its content.

PMID- 28453701
TI  - An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and
      prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223.
AB  - Background: Baseline clinical variables are prognostic for overall survival (OS)
      in patients with castration-resistant prostate cancer (CRPC). Their prognostic
      and predictive value with agents targeting bone metastases, such as radium-223,
      is not established. Patients and methods: The radium-223 ALSYMPCA trial enrolled
      patients with CRPC and symptomatic bone metastases. Prognostic potential of
      baseline variables was assessed using Cox models. Percentage changes in biomarker
      levels from baseline were evaluated during the trial period; changes from
      baseline to week 12 were evaluated for association with OS and surrogacy.
      Results: Eastern Cooperative Oncology Group performance status, total alkaline
      phosphatase (tALP), lactate dehydrogenase (LDH), and prostate-specific antigen
      (PSA) at baseline were associated with OS (P <= 0.0003) in the intent-to-treat
      population (radium-223, N = 614; placebo, N = 307). tALP declined from baseline
      within 4 weeks after beginning radium-223, by week 12 declining in 87% of radium
      223 and 23% of placebo patients (P < 0.001). LDH declined in 51% and 34% (P =
      0.003), whereas PSA declined in 27% and 14% (P = 0.160). Mean tALP change from
      baseline was 32.2% decrease with radium-223 and 37.2% increase with placebo.
      Radium-223 patients with tALP decline from baseline to week 12 (confirmed >=3
      weeks from week 12) had 55% lower risk of death (hazard ratio = 0.45; 95% CI 0.34
      0.61) versus those with no confirmed tALP decline. Proportional treatment effect
      (PTE) values for tALP, LDH, and PSA changes from baseline at week 12 as OS
      surrogate markers were 0.34 (95% CI: 0-0.746), 0.07 (95% CI: 0-0.211), and 0 (95%
      CI: 0-0.082), respectively. Conclusions: Significant tALP declines (versus
      placebo) occurred as early as 4 weeks after beginning radium-223 therapy. tALP or
      LDH declines at 12 weeks correlated with longer OS, but did not meet statistical
      surrogacy requirements. Dynamic changes in tALP and LDH during radium-223
      treatments may be useful to monitor, but do not serve as surrogates for survival.

PMID- 28453703
TI  - Heart dose exposure as prognostic marker after radiotherapy for resectable stage
      IIIA/B non-small-cell lung cancer: secondary analysis of a randomized trial.
AB  - Background: Heart exposure to ionizing irradiation can cause ischaemic heart
      disease. The partial heart volume receiving >=5 Gy (heartV5) was supposed to be
      an independent prognostic factor for survival after radiochemotherapy for locally
      advanced non-small-cell lung cancer (NSCLC). But validation of the latter
      hypothesis is needed under the concurrent risks of lung cancer patients. Patients
      and methods: The ESPATUE phase III trial recruited patients with potentially
      operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013.
      Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant
      radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine).
      Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B)
      and therefore were treated at two different total dose levels of radiotherapy.
      HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans,
      the prognostic value was analysed using multivariable proportional hazard
      analysis. Results: A total of 161 patients were randomized in ESPATUE, heartV5
      and MHD were obtained from the 3D radiotherapy plans for 155 of these
      [male/female:105/50, median age 58 (33-74) years, stage IIIA/IIIB: 54/101]. Power
      analysis revealed a power of 80% of this dataset to detect a prognostic value of
      heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify
      heartV5 as an independent prognostic factor for survival adjusting for tumour and
      clinical characteristics with [hazard ratio 1.005 (0.995-1.015), P = 0.30] or
      without lower lobe tumour location [hazard ratio 0.999 (0.986-1.012), P = 0.83].
      There was no influence of heartV5 on death without tumour progression. Tumour
      progression, and pneumonia were the leading causes of death representing 65% and
      14% of the observed deaths. Conclusions: HeartV5 could not be validated as an
      independent prognostic factor for survival after neoadjuvant or definitive
      conformal radiochemotherapy. Tumour progression was the predominant cause of
      death. Register No: Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation
      Protection).

PMID- 28453702
TI  - A phase 2, randomized, double-blind, placebo- controlled study of chemo
      immunotherapy combination using motolimod with pegylated liposomal doxorubicin in
      recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners
      study.
AB  - Background: A phase 2, randomized, placebo-controlled trial was conducted in
      women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and
      safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust
      innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a
      chemotherapeutic that induces immunogenic cell death. Patients and methods: Women
      with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 :
      1 to receive PLD in combination with blinded motolimod or placebo. Randomization
      was stratified by platinum-free interval (<=6 versus >6-12 months) and
      Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment
      cycles were repeated every 28 days until disease progression. Results: The
      addition of motolimod to PLD did not significantly improve overall survival (OS;
      log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log
      rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no
      synergistic or unexpected serious toxicity. Most patients experienced adverse
      events of fatigue, anemia, nausea, decreased white blood cells, and constipation.
      In pre-specified subgroup analyses, motolimod-treated patients who experienced
      injection site reactions (ISR) had a lower risk of death compared with those who
      did not experience ISR. Additionally, pre-treatment in vitro responses of immune
      biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving
      motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8
      single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair
      genes, and autoantibody biomarkers did not correlate with OS or PFS. Conclusions:
      The addition of motolimod to PLD did not improve clinical outcomes compared with
      placebo. However, subset analyses identified statistically significant
      differences in the OS of motolimod-treated patients on the basis of ISR and in
      vitro immune responses. Collectively, these data may provide important clues for
      identifying patients for treatment with immunomodulatory agents in novel
      combinations and/or delivery approaches. Trial registration: Clinicaltrials.gov,
      NCT 01666444.

PMID- 28453704
TI  - Genomic characterization of HER2-positive breast cancer and response to
      neoadjuvant trastuzumab and chemotherapy-results from the ACOSOG Z1041 (Alliance)
      trial.
AB  - Background: HER2 (ERBB2) gene amplification and its corresponding overexpression
      are present in 15-30% of invasive breast cancers. While HER2-targeted agents are
      effective treatments, resistance remains a major cause of death. The American
      College of Surgeons Oncology Group Z1041 trial (NCT00513292) was designed to
      compare the pathologic complete response (pCR) rate of distinct regimens of
      neoadjuvant chemotherapy and trastuzumab, but ultimately identified no
      difference. Patients and methods: In supplement to tissues from 37 Z1041 cases,
      11 similarly treated cases were obtained from a single institution study
      (NCT00353483). We have extracted genomic DNA from both pre-treatment tumor
      biopsies and blood of these 48 cases, and performed whole genome (WGS) and exome
      sequencing. Coincident with these efforts, we have generated RNA-seq profiles
      from 42 of the tumor biopsies. Among patients in this cohort, 24 (50%) achieved a
      pCR. Results: We have characterized the genomic landscape of HER2-positive breast
      cancer and investigated associations between genomic features and pCR. Cases
      assigned to the HER2-enriched subtype by RNA-seq analysis were more likely to
      achieve a pCR compared to the luminal, basal-like, or normal-like subtypes (19/27
      versus 3/15; P = 0.0032). Mutational events led to the generation of putatively
      active neoantigens, but were overall not associated with pCR. ERBB2 and GRB7 were
      the genes most commonly observed in fusion events, and genomic copy number
      analysis of the ERBB2 locus indicated that cases with either no observable or low
      level ERBB2 amplification were less likely to achieve a pCR (7/8 versus 17/40; P
      = 0.048). Moreover, among cases that achieved a pCR, tumors consistently
      expressed immune signatures that may contribute to therapeutic response.
      Conclusion: The identification of these features suggests that it may be possible
      to predict, at the time of diagnosis, those HER2-positive breast cancer patients
      who will not respond to treatment with chemotherapy and trastuzumab.
      ClinicalTrials.gov identifiers: NCT00513292, NCT00353483.

PMID- 28453705
TI  - Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic
      lymphocytic leukemia: results from a multicenter study of 683 patients.
AB  - Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL
      patients in the United States. However, there is no guidance as to their optimal
      sequence. Patients and methods: We conducted a multicenter, retrospective
      analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We
      examined demographics, discontinuation reasons, overall response rates (ORR),
      survival, and post-KI salvage strategies. Primary endpoint was progression-free
      survival (PFS). Results: A total of 683 patients were identified. Baseline
      characteristics were similar in the ibrutinib and idelalisib groups. ORR to
      ibrutinib and idelalisib as first KI was 69% and 81%, respectively. With a median
      follow-up of 17 months (range 1-60), median PFS and OS for the entire cohort were
      35 months and not reached. Patients treated with ibrutinib (versus idelalisib) as
      first KI had a significantly better PFS in all settings; front-line [hazard
      ratios (HR) 2.8, CI 1.3-6.3, P = 0.01], relapsed-refractory (HR 2.8, CI 1.9-4.1,
      P < 0.001), del17p (HR 2.0, CI 1.2-3.4, P = 0.008), and complex karyotype (HR
      2.5, CI 1.2-5.2, P = 0.02). At the time of initial KI failure, use of an
      alternate KI or venetoclax had a superior PFS when compared with
      chemoimmunotherapy. Furthermore, patients who discontinued ibrutinib due to
      progression or toxicity had marginally improved outcomes if they received
      venetoclax (ORR 79%) versus idelalisib (ORR 46%) (PFS HR .6, CI.3-1.0, P = 0.06).
      Conclusions: In the largest real-world experience of novel agents in CLL,
      ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting
      of KI failure, alternate KI or venetoclax therapy appear superior to
      chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure
      might be superior to idelalisib. These data support the need for trials testing
      sequencing strategies to optimize treatment algorithms.

PMID- 28453706
TI  - Somatic BRCA2 bi-allelic loss in the primary prostate cancer was associated to
      objective response to PARPi in a sporadic CRPC patient.

PMID- 28453707
TI  - The role of AR polyQ tract in male breast carcinoma: lesson from an SBMA case.

PMID- 28453709
TI  - A step towards the harmonization of clinical trials inform consent forms.

PMID- 28453708
TI  - Towards a global cancer knowledge network: dissecting the current international
      cancer genomic sequencing landscape.
AB  - Background: While next generation sequencing has enhanced our understanding of
      the biological basis of malignancy, current knowledge on global practices for
      sequencing cancer samples is limited. To address this deficiency, we developed a
      survey to provide a snapshot of current sequencing activities globally, identify
      barriers to data sharing and use this information to develop sustainable
      solutions for the cancer research community. Methods: A multi-item survey was
      conducted assessing demographics, clinical data collection, genomic platforms,
      privacy/ethics concerns, funding sources and data sharing barriers for sequencing
      initiatives globally. Additionally, respondents were asked as to provide the
      primary intent of their initiative (clinical diagnostic, research or
      combination). Results: Of 107 initiatives invited to participate, 59 responded
      (response rate = 55%). Whole exome sequencing (P = 0.03) and whole genome
      sequencing (P = 0.01) were utilized less frequently in clinical diagnostic than
      in research initiatives. Procedures to identify cancer-specific variants were
      heterogeneous, with bioinformatics pipelines employing different mutation
      calling/variant annotation algorithms. Measurement of treatment efficacy varied
      amongst initiatives, with time on treatment (57%) and RECIST (53%) being the most
      common; however, other parameters were also employed. Whilst 72% of initiatives
      indicated data sharing, its scope varied, with a number of restrictions in place
      (e.g. transfer of raw data). The largest perceived barriers to data harmonization
      were the lack of financial support (P < 0.01) and bioinformatics concerns (e.g.
      lack of interoperability) (P = 0.02). Capturing clinical data was more likely to
      be perceived as a barrier to data sharing by larger initiatives than by smaller
      initiatives (P = 0.01). Conclusions: These results identify the main barriers, as
      perceived by the cancer sequencing community, to effective sharing of cancer
      genomic and clinical data. They highlight the need for greater harmonization of
      technical, ethical and data capture processes in cancer sample sequencing
      worldwide, in order to support effective and responsible data sharing for the
      benefit of patients.

PMID- 28453710
TI  - Prescription of antibiotics to pre-school children from 2005 to 2014 in Japan: a
      retrospective claims database study.
AB  - Background: Antibiotics are the most frequently prescribed medications for
      children but inappropriate antibiotic prescribing is prevalent. The purpose of
      our study was to access the nationwide trend in antibiotic prescriptions, and to
      ascertain inappropriate prescribing for upper respiratory infections (URIs) in
      pre-school children in Japan. Methods: Data from the administrative claims
      database from 2005 January to 2014 September in Japan were examined. We
      identified outpatient antibiotic prescription claims and described prescription
      patterns of subjects who were followed from birth to 6 years of age. Logistic
      regression analyses were performed to estimate odd ratios (ORs) and their 95%
      confidence intervals (CIs) for factors associated with inappropriate antibiotic
      prescriptions. Results: Of 155 556 children in the database, 51.6% were male and
      48.4% were female. Antibiotics were prescribed for 66.4% of the cohort, with
      third generation cephalosporin the most prescribed (38.3%), followed by
      macrolides (25.8%), and penicillin (16.0%). Antibiotic prescriptions for non
      bacterial URIs were associated with male gender (OR = 1.06, CI: 1.05-1.07),
      facility scale, non-pediatrics (OR = 2.11, CI: 2.08-2.14) and out-of-hour visit
      (OR = 1.64, CI: 1.61-1.68). Conclusions: Third generation cephalosporins and
      macrolides are widely prescribed to Japanese pre-school children. Furthermore,
      inappropriate prescriptions for non-bacterial URIs are associated with increasing
      age, gender, facility characteristics, non-pediatrics and out-of-hour visits.

PMID- 28453711
TI  - Improving access to child health services at the community level in Zambia: a
      country case study on progress in child survival, 2000-2013.
AB  - Reductions in under-five mortality in Africa have not been sufficient to meet the
      Millennium Development Goal #4 (MDG#4) of reducing under-five mortality by two
      thirds by 2015. Nevertheless, 12 African countries have met MDG#4. We undertook a
      four country study to examine barriers and facilitators of child survival prior
      to 2015, seeking to better understand variability in success across countries.
      The current analysis presents indicator, national document, and qualitative data
      from key informants and community women describing the factors that have enabled
      Zambia to successfully reduce under-five mortality over the last 15 years and
      achieve MDG#4. Results identified a Zambian national commitment to ongoing reform
      of national health strategic plans and efforts to ensure universal access to
      effective maternal, neonatal and child health (MNCH) interventions, creating an
      environment that has promoted child health. Zambia has also focused on bringing
      health services as close to the family as possible through specific community
      health strategies. This includes actively involving community health workers to
      provide health education, basic MNCH services, and linking women to health
      facilities, while supplementing community and health facility work with twice
      yearly Child Health Weeks. External partners have contributed greatly to Zambia's
      MNCH services, and their relationships with the government are generally
      positive. As government funding increases to sustain MNCH services, national
      health strategies/plans are being used to specify how partners can fill gaps in
      resources. Zambia's continuing MNCH challenges include basic transportation,
      access-to-care, workforce shortages, and financing limitations. We highlight
      policies, programs, and implementation that facilitated reductions in under-five
      mortality in Zambia. These findings may inform how other countries in the African
      Region can increase progress in child survival in the post-MDG period.

PMID- 28453712
TI  - Use of performance metrics for the measurement of universal coverage for maternal
      care in Mexico.
AB  - This study provides evidence for those working in the maternal health metrics and
      health system performance fields, as well as those interested in achieving
      universal and effective health care coverage. Based on the perspective of
      continuity of health care and applying quasi-experimental methods to analyse the
      cross-sectional 2009 National Demographic Dynamics Survey (n = 14 414 women), we
      estimated the middle-term effects of Mexico's new public health insurance scheme,
      Seguro Popular de Salud (SPS) (vs women without health insurance) on seven
      indicators related to maternal health care (according to official guidelines):
      (a) access to skilled antenatal care (ANC); (b) timely ANC; (c) frequent ANC; (d)
      adequate content of ANC; (e) institutional delivery; (f) postnatal consultation
      and (g) access to standardized comprehensive antenatal and postnatal care (or the
      intersection of the seven process indicators). Our results show that 94% of all
      pregnancies were attended by trained health personnel. However, comprehensive
      access to ANC declines steeply in both groups as we move along the maternal
      healthcare continuum. The percentage of institutional deliveries providing
      timely, frequent and adequate content of ANC reached 70% among SPS women (vs
      64.7% in the uninsured), and only 57.4% of SPS-affiliated women received
      standardized comprehensive care (vs 53.7% in the uninsured group). In Mexico,
      access to comprehensive antenatal and postnatal care as defined by Mexican
      guidelines (in accordance to WHO recommendations) is far from optimal. Even
      though a positive influence of SPS on maternal care was documented, important
      challenges still remain. Our results identified key bottlenecks of the maternal
      healthcare continuum that should be addressed by policy makers through a
      combination of supply side interventions and interventions directed to social
      determinants of access to health care.

PMID- 28453713
TI  - Does charging different user fees for primary and secondary care affect first
      contacts with primary healthcare? A systematic review.
AB  - Policy-makers are increasingly considering charging users different fees between
      primary and secondary care (differential user charges) to encourage utilisation
      of primary health care in health systems with limited gate keeping. A systematic
      review was conducted to evaluate the impact of introducing differential user
      charges on service utilisation. We reviewed studies published in MEDLINE, EMBASE,
      the Cochrane library, EconLIT, HMIC, and WHO library databases from January 1990
      until June 2015. We extracted data from the studies meeting defined eligibility
      criteria and assessed study quality using an established checklist. We
      synthesized evidence narratively. Eight studies from six countries met our
      eligibility criteria. The overall study quality was low, with diversity in
      populations, interventions, settings, and methods. Five studies examined the
      introduction of or increase in user charges for secondary care, with four showing
      decreased secondary care utilisation, and three showing increased primary care
      utilisation. One study identified an increase in primary care utilisation after
      primary care user charges were reduced. The introduction of a non-referral charge
      in secondary care was associated with lower primary care utilisation in one
      study. One study compared user charges across insurance plans, associating higher
      charges in secondary care with higher utilisation in both primary and secondary
      care. Overall, the impact of introducing differential user-charges on primary
      care utilisation remains uncertain. Further research is required to understand
      their impact as a demand side intervention, including implications for health
      system costs and on utilisation among low-income patients.

PMID- 28453714
TI  - Evaluating the effect of integrated microfinance and health interventions: an
      updated review of the evidence.
AB  - Background: Solutions delivered within firm sectoral boundaries are inadequate in
      achieving income security and better health for poor populations. Integrated
      microfinance and health interventions leverage networks of women to promote
      financial inclusion, build livelihoods, and safeguard against high cost
      illnesses. Our understanding of the effect of integrated interventions has been
      limited by variability in intervention, outcome, design, and methodological
      rigour. This systematic review synthesises the literature through 2015 to
      understand the effect of integrated microfinance and health programs. Methods: We
      searched PubMed, Scopus, Embase, EconLit, and Global Health databases and sourced
      bibliographies, identifying 964 articles exclusive of duplicates. Title,
      abstract, and full text review yielded 35 articles. Articles evaluated the effect
      of intentionally integrated microfinance and health programs on client outcomes.
      We rated the quality of evidence for each article. Results: Most interventions
      combined microfinance with health education, which demonstrated positive effects
      on health knowledge and behaviours, though not health status. Among programs that
      integrated microfinance with other health components ( i.e. health micro
      insurance, linkages to health providers, and access to health products), results
      were generally positive but mixed due to the smaller number and quality of
      studies. Interventions combining multiple health components in a given study
      demonstrated positive effects, though it was unclear which component was driving
      the effect. Most articles (57%) were moderate in quality. Discussion: Integrated
      microfinance and health education programs were effective, though longer
      intervention periods are necessary to measure more complex pathways to health
      status. The effect of microfinance combined with other health components was less
      clear. Stronger randomized research designs with multiple study arms are required
      to improve evidence and disentangle the effects of multiple component
      microfinance and health interventions. Few studies attempted to understand
      changes in economic outcomes, limiting our understanding of the relationship
      between health and income effects.

PMID- 28453715
TI  - The inequity of inpatient services in rural areas and the New-Type Rural
      Cooperative Medical System (NRCMS) in China: repeated cross sectional analysis.
AB  - Objective : The main aim of the New-type Rural Cooperative Medical System (NRCMS)
      put into effect in 2003 was to reduce financial barriers in accessing health care
      services among vulnerable populations. The aim of this study was to assess the
      association between NRCMS and income related inequality in hospital utilization
      among rural inhabitants in Jiangxi Province, China. Methods : A multistage
      stratified random cluster sampling method was adopted to select 1838, 1879, and
      1890 households as participants in 2003/2004, 2008 and 2014, respectively. The
      Erreygers Concentration index (EI) of two measures of hospital inpatient care
      including admission to hospital and hospital avoidance, were calculated to
      measure income-related inequality. The decomposition of the EI was performed to
      characterize the contributions of socioeconomic and need factors to the measured
      inequality. Results : An affluent-focused (pro-rich) inequity was observed for
      hospital admission adjusting for need factors over time. The level of inequity
      for hospital admission decreased dramatically, while hospital avoidance decreased
      marginally, and with a high value (EI, -0.0176) in 2008. The implementation of
      the NRCMS was associated with decreased inequity in 2008 and in 2014, but the
      associations were limited. Income contributed the most to the inequality of
      hospital utilization each year. Conclusion : The coverage of the NRCMS expanded
      to cover nearly all rural inhabitants in Jiangxi province by 2014 and was
      associated with a very small reduction in inequalities in admission to hospital.
      In order to increase equitable access to health care, additional financial
      protections for vulnerable populations are needed. Improving the relatively low
      level of medical services in township hospitals, and low rate of reimbursement
      and financial assistance with the NRCMS is recommended.

PMID- 28453716
TI  - Inflated medicine prices in Vietnam: a qualitative study.
AB  - One third of the world's population lacks regular access to essential medicines
      partly because of the high cost of medicines. In Vietnam, the cost to patients of
      medicines was 47 times the international reference price for originator brands
      and 11 times the price for generic equivalents in the public sector. In this
      article, we report the results of a qualitative study conducted to identify the
      principal reasons for inflated medicine prices in Vietnam.Between April 2008 and
      December 2009, 29 semi-structured interviews were conducted with staff from
      pharmaceutical companies, private pharmacies, the Ministry of Health, and the
      Ministry of Finance of Vietnam. Study participants were recruited using a
      combination of purposive and snowball sampling techniques. Interviews were
      recorded, transcribed and coded using NVivo8(r) software and analyzed using a
      framework of structure-conduct-performance (SCP).Participants attributed high
      prices of originator medicines to a monopoly of supply. The prices of generic
      medicines were also considered to be excessive, reportedly due to the need to
      recoup the cost of financial inducements paid to prescribers and procurement
      officers. These inducements constituted a dominant cost component of the end
      price of generic medicines. Poor market intelligence about current world prices,
      as well as failure to achieve economies of scale because of unwarranted
      duplication in pharmaceutical production and distribution system were also
      factors contributing to high prices. This was reported to be further compounded
      by multiple layers in the supply chain and unregulated retail mark-ups.To address
      these problems a multifaceted approach is needed encompassing policy and
      legislative responses. Policy options include establishing effective monitoring
      of medicine quality assurance, procurement, distribution and use. Rationalization
      of the domestic pharmaceutical production and distribution system to achieve
      economies of scale is also required. Appropriate legal responses include
      collaborations with the justice and law enforcement sectors to enforce existing
      laws.

PMID- 28453718
TI  - Cost-effectiveness analysis of malaria rapid diagnostic tests for appropriate
      treatment of malaria at the community level in Uganda.
AB  - In Sub-Saharan Africa, malaria remains a major cause of morbidity and mortality
      among children under 5, due to lack of access to prompt and appropriate diagnosis
      and treatment. Many countries have scaled-up community health workers (CHWs) as a
      strategy towards improving access. The present study was a cost-effectiveness
      analysis of the introduction of malaria rapid diagnostic tests (mRDTs) performed
      by CHWs in two areas of moderate-to-high and low malaria transmission in rural
      Uganda. CHWs were trained to perform mRDTs and treat children with artemisinin
      based combination therapy (ACT) in the intervention arm while CHWs offered
      treatment based on presumptive diagnosis in the control arm. Data on the
      proportion of children with fever 'appropriately treated for malaria with ACT'
      were captured from a randomised trial. Health sector costs included: training of
      CHWs, community sensitisation, supervision, allowances for CHWs and provision of
      mRDTs and ACTs. The opportunity costs of time utilised by CHWs were estimated
      based on self-reporting. Household costs of subsequent treatment-seeking at
      public health centres and private health providers were captured in a sample of
      households. mRDTs performed by CHWs was associated with large improvements in
      appropriate treatment of malaria in both transmission settings. This resulted in
      low incremental costs for the health sector at US$3.0 per appropriately treated
      child in the moderate-to-high transmission area. Higher incremental costs at
      US$13.3 were found in the low transmission area due to lower utilisation of CHW
      services and higher programme costs. Incremental costs from a societal
      perspective were marginally higher. The use of mRDTs by CHWs improved the
      targeting of ACTs to children with malaria and was likely to be considered a cost
      effective intervention compared to a presumptive diagnosis in the moderate-to
      high transmission area. In contrast to this, in the low transmission area with
      low attendance, RDT use by CHWs was not a low cost intervention.

PMID- 28453717
TI  - Reaching the global target to reduce stunting: an investment framework.
AB  - Childhood stunting, being short for one's age, has life-long consequences for
      health, human capital and economic growth. Being stunted in early childhood is
      associated with slower cognitive development, reduced schooling attainment and
      adult incomes decreased by 5-53%. The World Health Assembly has endorsed global
      nutrition targets including one to reduce the number of stunted children under
      five by 40% by 2025. The target has been included in the Sustainable Development
      Goals (SDG target 2.2). This paper estimates the cost of achieving this target
      and develops scenarios for generating the necessary financing. We focus on a key
      intervention package for stunting (KIPS) with strong evidence of effectiveness.
      Annual scale-up costs for the period of 2016-25 were estimated for a sample of 37
      high burden countries and extrapolated to all low and middle income countries.
      The Lives Saved Tool was used to model the impact of the scale-up on stunting
      prevalence. We analysed data on KIPS budget allocations and expenditure by
      governments, donors and households to derive a global baseline financing
      estimate. We modelled two financing scenarios, a 'business as usual', which
      extends the current trends in domestic and international financing for nutrition
      through 2025, and another that proposes increases in financing from all sources
      under a set of burden-sharing rules. The 10-year financial need to scale up KIPS
      is US$49.5 billion. Under 'business as usual', this financial need is not met and
      the global stunting target is not reached. To reach the target, current financing
      will have to increase from US$2.6 billion to US$7.4 billion a year on average.
      Reaching the stunting target is feasible but will require large coordinated
      investments in KIPS and a supportive enabling environment. The example of HIV
      scale-up over 2001-11 is instructive in identifying the factors that could drive
      such a global response to childhood stunting.

PMID- 28453719
TI  - Civil war, contested sovereignty and the limits of global health partnerships: A
      case study of the Syrian polio outbreak in 2013.
AB  - States and the World Health Organization (WHO), an international organization
      that is mandated to respect the sovereignty of its member states, are still the
      leading actors in global health. This paper explores how this discrepancy
      inhibits the ability of global health partnerships to implement programmes in
      conflict-affected areas that are under the de facto control of rebel
      organizations. We concentrate on a single crucial case, the polio outbreak in
      Syria in 2013, analysing a variety of qualitative data-twenty semi-structured
      interviews with key actors, official documents, and media reports-in order to
      investigate the events that preceded and followed this event. The WHO's mandate
      to respect the Syrian government's sovereignty inhibited its ability to prevent,
      identify and contain the outbreak because the Assad regime refused it permission
      to operate in rebel-controlled areas. The polio outbreak was identified and
      contained by organizations operating outside the United Nations (UN) system that
      disregarded the Syrian government's sovereignty claims and cooperated with the
      militants. Thus, we identify a serious problem with so-called global health
      partnerships in which nation states and international organizations remain key
      actors. Such initiatives function well in situations where there is a capable
      state that is concerned with the welfare of its citizens and has exclusivity of
      jurisdiction over its territory. But they can encounter difficulties in areas
      where rebels challenge the state's sovereignty. Although the response to the
      Syrian polio outbreak was ultimately effective, it was reactive, ad hoc, slow and
      relied on personnel who had little experience. Global health partnerships would
      be more effective in conflict-affected areas if they put in place proactive and
      institutionalized plans to implement their programmes in regions outside
      government control.

PMID- 28453720
TI  - 'Seeking affluent neighbourhoods?' a time-trend analysis of geographical
      distribution of hospitals in the Megacity of Tehran.
AB  - Objective: Access to hospitals in megacities in low and middle income countries
      might be hampered by travel barriers and distance. We assessed the 'inverse care
      law' hypothesis: whether hospitals tended to be built in the relatively better
      off areas through the time. Methods: A longitudinal time-series study (1966 to
      2011) in Tehran to measure inequality in the distribution of hospital beds. We
      assessed correlations between the district socioeconomic status and availability
      of hospital beds via regression analyses, estimated correlation, Gini and
      concentration indices, and used GIS models to map hospital distributions through
      time. Finding: We found a clear relationship between socioeconomic status and
      number of hospital beds per capita ( P -values <0.05). Gini coefficients were
      about 0.6 and 0.8 for public and private beds, respectively. A third of the
      variations in hospital bed distribution was explained by the welfare status of
      the district. For every extra residential room per capita, 130 to 280 extra beds
      were observed per ten thousand population at the district level. In 2011, out of
      162 hospitals, 110 were located in six districts around the centre and northern
      part of the city. During the time period only two private hospitals were built in
      relatively disadvantaged districts. Conclusion: Over a period of about fifty
      years new hospitals had been established in the relatively affluent areas of the
      city and the relationship between socioeconomic status of district with total,
      private and public beds were direct and intensive. Results indicate the problem
      of inequality may remain over time and be resistant to policy initiatives and
      major political changes.

PMID- 28453721
TI  - Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a
      randomized controlled cross-over trial.
AB  - Aims: To determine the clinical impact of lipoprotein apheresis in patients with
      refractory angina and raised lipoprotein(a) > 500 mg/L on the primary end point
      of quantitative myocardial perfusion, as well as secondary end points including
      atheroma burden, exercise capacity, symptoms, and quality of life. Methods: We
      conducted a single-blinded randomized controlled trial in 20 patients with
      refractory angina and raised lipoprotein(a) > 500 mg/L, with 3 months of blinded
      weekly lipoprotein apheresis or sham, followed by crossover. The primary endpoint
      was change in quantitative myocardial perfusion reserve (MPR) assessed by
      cardiovascular magnetic resonance. Secondary endpoints included measures of
      atheroma burden, exercise capacity, symptoms and quality of life. Results: The
      primary endpoint, namely MPR, increased following apheresis (0.47; 95% CI 0.31
      0.63) compared with sham (-0.16; 95% CI - 0.33-0.02) yielding a net treatment
      increase of 0.63 (95% CI 0.37-0.89; P < 0.001 between groups). Improvements with
      apheresis compared with sham also occurred in atherosclerotic burden as assessed
      by total carotid wall volume (P < 0.001), exercise capacity by the 6 min walk
      test (P = 0.001), 4 of 5 domains of the Seattle angina questionnaire (all P <
      0.02) and quality of life physical component summary by the short form 36 survey
      (P = 0.001). Conclusion: Lipoprotein apheresis may represent an effective novel
      treatment for patients with refractory angina and raised lipoprotein(a) improving
      myocardial perfusion, atheroma burden, exercise capacity and symptoms.

PMID- 28453722
TI  - Accuracy of MDCT and CBCT in three-dimensional evaluation of the oropharynx
      morphology.
AB  - Objective: To assess the accuracy of five different computed tomography (CT)
      scanners for the evaluation of the oropharynx morphology. Methods: An existing
      cone-beam computed tomography (CBCT) data set was used to fabricate an
      anthropomorphic phantom of the upper airway volume that extended from the uvula
      to the epiglottis (oropharynx) with known dimensions (gold standard). This
      phantom was scanned using two multi-detector row computed tomography (MDCT)
      scanners (GE Discovery CT750 HD, Siemens Somatom Sensation) and three CBCT
      scanners (NewTom 5G, 3D Accuitomo 170, Vatech PaX Zenith 3D). All CT images were
      segmented by two observers and converted into standard tessellation language
      (STL) models. The volume and the cross-sectional area of the oropharynx were
      measured on the acquired STL models. Finally, all STL models were registered and
      compared with the gold standard. Results: The intra- and inter-observer
      reliability of the oropharynx segmentation was fair to excellent. The most
      accurate volume measurements were acquired using the Siemens MDCT (98.4%; 14.3
      cm3) and Vatech CBCT (98.9%; 14.4 cm3) scanners. The GE MDCT, NewTom 5G CBCT, and
      Accuitomo CBCT scanners resulted in smaller volumes, viz., 92.1% (13.4 cm3),
      91.5% (13.3 cm3), and 94.6% (13.8 cm3), respectively. The most accurate cross
      sectional area measurements were acquired using the Siemens MDCT (94.6%; 282.4
      mm2), Accuitomo CBCT (95.1%; 283.8 mm2), and Vatech CBCT (95.3%; 284.5 mm2)
      scanners. The GE MDCT and NewTom 5G CBCT scanners resulted in smaller areas,
      viz., 89.3% (266.5 mm2) and 89.8% (268.0 mm2), respectively. Limitations: Images
      of the phantom were acquired using the vendor-supplied default airway scanning
      protocol for each scanner. Conclusion: Significant differences were observed in
      the volume and cross-sectional area measurements of the oropharynx acquired using
      different MDCT and CBCT scanners. The Siemens MDCT and the Vatech CBCT scanners
      were more accurate than the GE MDCT, NewTom 5G, and Accuitomo CBCT scanners. In
      clinical settings, CBCT scanners offer an alternative to MDCT scanners in the
      assessment of the oropharynx morphology.

PMID- 28453724
TI  - A Generative Angular Model of Protein Structure Evolution.
AB  - Recently described stochastic models of protein evolution have demonstrated that
      the inclusion of structural information in addition to amino acid sequences leads
      to a more reliable estimation of evolutionary parameters. We present a
      generative, evolutionary model of protein structure and sequence that is valid on
      a local length scale. The model concerns the local dependencies between sequence
      and structure evolution in a pair of homologous proteins. The evolutionary
      trajectory between the two structures in the protein pair is treated as a random
      walk in dihedral angle space, which is modeled using a novel angular diffusion
      process on the two-dimensional torus. Coupling sequence and structure evolution
      in our model allows for modeling both "smooth" conformational changes and
      "catastrophic" conformational jumps, conditioned on the amino acid changes. The
      model has interpretable parameters and is comparatively more realistic than
      previous stochastic models, providing new insights into the relationship between
      sequence and structure evolution. For example, using the trained model we were
      able to identify an apparent sequence-structure evolutionary motif present in a
      large number of homologous protein pairs. The generative nature of our model
      enables us to evaluate its validity and its ability to simulate aspects of
      protein evolution conditioned on an amino acid sequence, a related amino acid
      sequence, a related structure or any combination thereof.

PMID- 28453723
TI  - GTP binding regulates cellular localization of Parkinson's disease-associated
      LRRK2.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) comprise the most common cause
      of familial Parkinson's disease (PD), and sequence variants modify risk for
      sporadic PD. Previous studies indicate that LRRK2 interacts with microtubules
      (MTs) and alters MT-mediated vesicular transport processes. However, the
      molecular determinants within LRRK2 required for such interactions have remained
      unknown. Here, we report that most pathogenic LRRK2 mutants cause relocalization
      of LRRK2 to filamentous structures which colocalize with a subset of MTs, and an
      identical relocalization is seen upon pharmacological LRRK2 kinase inhibition.
      The pronounced colocalization with MTs does not correlate with alterations in
      LRRK2 kinase activity, but rather with increased GTP binding. Synthetic mutations
      which impair GTP binding, as well as LRRK2 GTP-binding inhibitors profoundly
      interfere with the abnormal localization of both pathogenic mutant as well as
      kinase-inhibited LRRK2. Conversely, addition of a non-hydrolyzable GTP analog to
      permeabilized cells enhances the association of pathogenic or kinase-inhibited
      LRRK2 with MTs. Our data elucidate the mechanism underlying the increased MT
      association of select pathogenic LRRK2 mutants or of pharmacologically kinase
      inhibited LRRK2, with implications for downstream MT-mediated transport events.

PMID- 28453725
TI  - Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart
      failure in experimental peripartum cardiomyopathy.
AB  - Aims: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction
      developing in the peripartum phase in previously healthy women. Relaxin-2 is a
      pregnancy hormone with potential beneficial effects in heart failure patients. We
      evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent
      in PPCM. Methods and results: In healthy peripartum women, serum Relaxin-2 levels
      (measured by ELISA in the second half of pregnancy) were elevated showing a
      decreasing trend in the first postpartum week and returned to non-pregnant levels
      thereafter. In PPCM patients diagnosed in the first postpartum week, serum
      Relaxin-2 levels were lower compared to healthy postpartum stage-matched
      controls. In PPCM patients diagnosed later (0.5-10 months postpartum) Relaxin-2
      levels were in the range of non-pregnant controls and not different from healthy
      postpartum stage-matched controls. In mice, serum Relaxin-1 (functional
      equivalent of human Relaxin-2) was increased late in pregnancy and rapidly
      cleared in the first postpartum week. In mice with PPCM due to a cardiomyocyte
      specific knockout of STAT3 (CKO) neither low nor high dose of recombinant Relaxin
      2 (serelaxin, sRlx-LD: 30 ug/kg/day; sRlx-HD: 300 ug/kg/day) affected cardiac
      fibrosis, inflammation and heart failure but sRlx-HD increased
      capillary/cardiomyocyte ratio. sRlx-HD significantly increased heart/body weight
      ratio and cardiomyocyte cross-sectional area in postpartum CKO and wild-type mice
      without changing the foetal gene expression program (ANP or beta-MHC). sRlx-HD
      augmented plasma Prolactin levels in both genotypes, which induced cardiac
      activation of STAT5. In vitro analyses showed that Prolactin induces
      cardiomyocyte hypertrophy via activation of STAT5. Conclusion: Although Relaxin-2
      levels seemed lower in PPCM patients diagnosed early postpartum, we observed a
      high pregnancy-related variance of serum Relaxin-2 levels peripartum making it
      unsuitable as a biomarker for this condition. Supplementation with sRlx may
      contribute to angiogenesis and compensatory hypertrophy in the diseased heart,
      but the effects are not sufficient to prevent heart failure in an experimental
      PPCM model.

PMID- 28453726
TI  - Osteopontin RNA aptamer can prevent and reverse pressure overload-induced heart
      failure.
AB  - Aims: Cardiac myocyte hypertrophy, the main compensatory response to chronic
      stress in the heart often progresses to a state of decompensation that can lead
      to heart failure. Osteopontin (OPN) is an effector for extracellular signalling
      that induces myocyte growth and fibrosis. Although increased OPN activity has
      been observed in stressed myocytes and fibroblasts, the detailed and long term
      effects of blocking OPN signalling on the heart remain poorly defined. Targeting
      cardiac OPN protein by an RNA aptamer may be beneficial for tuning down OPN
      pathologic signalling. We aimed to demonstrate the therapeutic effects of an OPN
      RNA aptamer on cardiac dysfunction. Methods and results: In vivo, we show that in
      a mouse model of pressure overload, treating at the time of surgeries with an OPN
      aptamer prevented cardiomyocyte hypertrophy and cardiac fibrosis, blocked OPN
      downstream signalling (PI3K and Akt phosphorylation), reduced expression of
      extracellular matrix (Lum, Col3a1, Fn1) and hypertrophy (Nppa, Nppb) genes, and
      prevented cardiac dysfunction. Treating at two months post-surgeries with the OPN
      aptamer reversed cardiac dysfunction and fibrosis and myocyte hypertrophy. While
      genetic homozygous deletion of OPN reduced myocardial wall thickness,
      surprisingly cardiac function and myocardial fibrosis, specifically collagen
      deposition and myofibroblast infiltration, were worse compared with wild type
      mice at three months of pressure overload. Conclusion: Taken together, these data
      demonstrate that tuning down cardiac OPN signalling by an OPN RNA aptamer is a
      novel and effective approach for preventing cardiac hypertrophy and fibrosis,
      improving cardiac function, and reversing pressure overload-induced heart
      failure.

PMID- 28453727
TI  - Endothelial glycocalyx breakdown is mediated by angiopoietin-2.
AB  - Aims: The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the
      luminal surface of the endothelium, provides a first vasoprotective barrier
      against vascular leakage and adhesion in sepsis and vessel inflammation.
      Angiopoietin-2 (Angpt-2), an antagonist of the endothelium-stabilizing receptor
      Tie2 secreted by endothelial cells, promotes vascular permeability through
      cellular contraction and junctional disintegration. We hypothesized that Angpt-2
      might also mediate the breakdown of the eGC. Methods and results: Using confocal
      and atomic force microscopy, we show that exogenous Angpt-2 induces a rapid loss
      of the eGC in endothelial cells in vitro. Glycocalyx deterioration involves the
      specific loss of its main constituent heparan sulphate, paralleled by the
      secretion of the heparan sulphate-specific heparanase from late
      endosomal/lysosomal stores. Corresponding in vivo experiments revealed that
      exogenous Angpt-2 leads to heparanase-dependent eGC breakdown, which contributes
      to plasma leakage and leukocyte recruitment in vivo. Conclusion: Our data
      indicate that eGC breakdown is mediated by Angpt-2 in a non-redundant manner.

PMID- 28453728
TI  - Cardiac mGluR1 metabotropic receptors in cardioprotection.
AB  - Aims: In a previous study using a genome-wide microarray strategy, we identified
      metabotropic glutamate receptor 1 (mGluR1) as a putative cardioprotective
      candidate in ischaemic postconditioning (PostC). In the present study, we
      investigated the role of cardiac mGluR1 receptors during cardioprotection against
      myocardial ischaemia-reperfusion injury in the mouse myocardium. Methods and
      results: mGluR1 activation by glutamate administered 5 min before reperfusion in
      C57Bl/6 mice subjected to a myocardial ischaemia protocol strongly decreased both
      infarct size and DNA fragmentation measured at 24 h reperfusion. This
      cardioprotective effect was mimicked by the mGluR1 agonist, DHPG (10 MUM), and
      abolished when glutamate was coinjected with the mGluR1 antagonist YM298198 (100
      nM). Wortmannin (100 nM), an inhibitor of PI3-kinase, was able to prevent
      glutamate-induced cardioprotection. A glutamate bolus at the onset of reperfusion
      failed to protect the heart of mGluR1 knockout mice subjected to a myocardial
      ischaemia-reperfusion protocol, although PostC still protected the mGluR1 KO
      mice. Glutamate-treatment improved post-infarction functional recovery as
      evidenced by an echocardiographic study performed 15 days after treatment and by
      a histological evaluation of fibrosis 21 days post-treatment. Interestingly,
      restoration of functional mGluR1s by a PostC stimulus was evidenced at the
      transcriptional level. Since mGluR1s were localized at the surface membrane of
      cardiomyocytes, they might contribute to the cardioprotective effect of ischaemic
      PostC as other Gq-coupled receptors. Conclusion: This study provides the first
      demonstration that mGluR1 activation at the onset of reperfusion induces
      cardioprotection and might represent a putative strategy to prevent ischaemia
      reperfusion injury.

PMID- 28453730
TI  - Reply: Glycine as a key element of remote ischaemic conditioning cardioprotective
      signalling.

PMID- 28453729
TI  - Ablation of periostin inhibits post-infarction myocardial regeneration in
      neonatal mice mediated by the phosphatidylinositol 3 kinase/glycogen synthase
      kinase 3beta/cyclin D1 signalling pathway.
AB  - Aims: To resolve the controversy as to whether periostin plays a role in
      myocardial regeneration after myocardial infarction (MI), we created a neonatal
      mouse model of MI to investigate the influence of periostin ablation on
      myocardial regeneration and clarify the underlying mechanisms. Methods and
      results: Neonatal periostin-knockout mice and their wildtype littermates were
      subjected to MI or sham surgery. In the wildtype mice after MI, fibrosis was
      detectable at 3 days and fibrotic tissue was completely replaced by regenerated
      myocardium at 21 days. In contrast, in the knockout mice, significant fibrosis in
      the infarcted area was present at even 3 weeks after MI. Levels of phosphorylated
      histone 3 and aurora B in the myocardium, detected by immunofluorescence and
      western blotting, were significantly lower in knockout than in wildtype mice at 7
      days after MI. Similarly, angiogenesis was decreased in the knockout mice after
      MI. Expression of both the endothelial marker CD-31 and alpha-smooth muscle actin
      was markedly lower in the knockout than in wildtype mice at 7 days after MI. The
      knockout MI group had elevated levels of glycogen synthase kinase (GSK) 3beta and
      decreased phosphatidylinositol 3-kinase (PI3K), phosphorylated serine/threonine
      protein kinase B (p-Akt), and cyclin D1, compared with the wildtype MI group.
      Similar effects were observed in experiments using cultured cardiomyocytes from
      neonatal wildtype or periostin knockout mice. Administration of SB216763, a
      GSK3beta inhibitor, to knockout neonatal mice decreased myocardial fibrosis and
      increased angiogenesis in the infarcted area after MI. Conclusion: Ablation of
      periostin suppresses post-infarction myocardial regeneration by inhibiting the
      PI3K/GSK3beta/cyclin D1 signalling pathway, indicating that periostin is
      essential for myocardial regeneration.

PMID- 28453732
TI  - Corrigendum to: Multilevel analyses of SCN5A mutations in arrhythmogenic right
      ventricular dysplasia/cardiomyopathy suggest non-canonical mechanisms for disease
      pathogenesis.

PMID- 28453733
TI  - Corrigendum to: A landscape of circular RNA expression in the human heart.

PMID- 28453731
TI  - Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A
      and SEMA6D.
AB  - Aims: Vessel maturation involves the recruitment of mural cells such as pericytes
      and smooth muscle cells. Laminar shear stress is a major trigger for vessel
      maturation, but the molecular mechanisms by which shear stress affects
      recruitment of pericytes are unclear. MicroRNAs (miRs) are small non-coding RNAs,
      which post-transcriptionally control gene expression. The aim of the present
      study was to unveil the mechanism by which shear stress-regulated microRNAs
      contribute to vessel maturation. Methods and results: Here, we show that laminar
      shear stress increased miR-27a and miR-27b expression in vitro and in ex vivo in
      mouse femoral artery explants. Overexpression of miR-27b in endothelial cells
      increased pericyte adhesion and pericyte recruitment in vitro. In vitro barrier
      function of endothelial-pericyte co-cultures was augmented by miR-27b
      overexpression, whereas inhibition of miR-27a/b reduced adhesion and pericyte
      coverage and decreased barrier functions. In vivo, pharmacological inhibition of
      miR-27a/b by locked nucleic acid antisense oligonucleotides significantly reduced
      pericyte coverage and increased water content in the murine uterus. MiR-27b
      overexpression repressed semaphorins (SEMA), which mediate repulsive signals, and
      the vessel destabilizing human but not mouse Angiopoietin-2 (Ang-2). Silencing of
      SEMA6A and SEMA6D rescued the reduced pericyte adhesion by miR-27 inhibition.
      Furthermore, inhibition of SEMA6D increased barrier function of an endothelial
      pericyte co-culture in vitro. Conclusion: The present study demonstrates for the
      first time that shear stress-regulated miR-27b promotes the interaction of
      endothelial cells with pericytes, partly by repressing SEMA6A and SEMA6D.

PMID- 28453735
TI  - Layer upon layer: the functional consequences of disrupting the glycocalyx
      endothelial barrier in vivo and in vitro.

PMID- 28453736
TI  - Analysis of genes to predict the effects of proprotein convertase
      subtilisin/kexin type 9-inhibitors and statins.

PMID- 28453734
TI  - Novel targets and future strategies for acute cardioprotection: Position Paper of
      the European Society of Cardiology Working Group on Cellular Biology of the
      Heart.
AB  - Ischaemic heart disease and the heart failure that often results, remain the
      leading causes of death and disability in Europe and worldwide. As such, in order
      to prevent heart failure and improve clinical outcomes in patients presenting
      with an acute ST-segment elevation myocardial infarction and patients undergoing
      coronary artery bypass graft surgery, novel therapies are required to protect the
      heart against the detrimental effects of acute ischaemia/reperfusion injury
      (IRI). During the last three decades, a wide variety of ischaemic conditioning
      strategies and pharmacological treatments have been tested in the clinic-however,
      their translation from experimental to clinical studies for improving patient
      outcomes has been both challenging and disappointing. Therefore, in this Position
      Paper of the European Society of Cardiology Working Group on Cellular Biology of
      the Heart, we critically analyse the current state of ischaemic conditioning in
      both the experimental and clinical settings, provide recommendations for
      improving its translation into the clinical setting, and highlight novel
      therapeutic targets and new treatment strategies for reducing acute myocardial
      IRI.

PMID- 28453737
TI  - Dr Smart talks to Prof Pries and Prof Dirnagl on animal experimentation in
      biomedical research.

PMID- 28453738
TI  - Transfer of mitochondria after stroke: a new hope for cardioprotection coming
      from the brain?

PMID- 28453739
TI  - Relaxin: reproductive safeguard turned cardiac?

PMID- 28453740
TI  - Enhanced Coupling Within Gonadotropic and Adrenocorticotropic Axes by Moderate
      Exercise in Healthy Men.
AB  - Context: Exercise elicits incompletely defined adaptations of metabolic and
      endocrine milieu, including the gonadotropic and corticotropic axes. Objective:
      To quantify the impact of acute exercise on coordinate luteinizing hormone (LH)
      and testosterone (T) and adrenocorticotropic hormone (ACTH) and cortisol
      secretion in healthy men in relation to age. Participants and Design:
      Prospectively randomized, within-subject crossover study in 23 men aged 19 to 77
      years old. Subjects underwent rest and 30 minutes of mixed exercise at 65% of
      maximal aerobic capacity with 10-minute blood sampling between 7:00 am and 1:00
      pm, 2 weeks apart. Main Outcome Measures: Incremental changes in LH, T, ACTH, and
      cortisol concentrations, the feedforward and feedback strength between exercise
      and rest, quantified by approximate entropy (ApEn), and bihormonal synchrony,
      quantitated by cross-ApEn. Results: Mean hourly exercise-minus-rest LH and ACTH
      increments increased from -0.055 +/- 0.187 to 0.755 +/- 0.245 IU/L (P = 0.003)
      and from 2.9 +/- 2.2 to 71.2 +/- 16.1 ng/L (P < 0.0001), respectively, during
      exercise. T and cortisol increments increased concurrently from -9.6 +/- 16.7 to
      47.6 +/- 17.1 ng/dL (P < 0.0001) and 0.45 +/- 0.76 to 7.27 +/- 0.64 ug/dL (P <
      0.0001), respectively. During exercise, feedforward and feedback LH-T and ACTH
      cortisol cross-ApEn decreased markedly quantifying enhanced hormonal coupling.
      Conclusions: Acute moderate mixed exercise in healthy men rapidly enhances
      feedforward LH-T and ACTH-cortisol coordination and reciprocal feedback within
      the gonadotropic and corticotropic axes. In principle, enhancement of both LH-T
      and ACTH-cortisol secretory synchrony by exercise could reflect augmented
      coupling between brain-testicular and brain-adrenal neural outflow.

PMID- 28453741
TI  - Application of Pheromone Traps for Managing Hessian Fly (Diptera: Cecidomyiidae)
      in the Southern Great Plains.
AB  - The Hessian fly, Mayetiola destructor Say, is an important pest of winter wheat
      in the Southern Great Plains of the United States. As larvae feed behind the leaf
      sheath, infestations often go undetected until crop damage is evident, and there
      are no remedial actions that can prevent economic loss once a field is infested.
      The recent discovery of the sex-attractant pheromone of the Hessian fly provides
      an opportunity to use pheromone traps to detect and monitor adult activity and
      potentially better manage this pest. Adult male Hessian fly activity was
      monitored during 4 yr at six locations from northcentral Oklahoma, 36 degrees  N
      latitude, south to central Texas, 31 degrees  N latitude. In Oklahoma, trap
      captures were low in the fall, no flies were captured during the winter, and the
      largest number of flies was captured in the spring. However, in southcentral
      Texas, adults were captured throughout the fall, winter, and in the spring when
      trap captures were again the greatest. The relationship between trap captures and
      density of Hessian fly larvae per tiller was investigated during the fall and
      spring. Although large numbers of adults (>100 per trap per day) were often
      captured, economic infestation of larvae rarely developed. Results identify
      optimum times for field sampling to determine immature Hessian fly infestations
      in wheat in Oklahoma and Texas.

PMID- 28453742
TI  - Blinded Contractility Analysis in hiPSC-Cardiomyocytes in Engineered Heart Tissue
      Format: Comparison With Human Atrial Trabeculae.
AB  - Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) may serve
      as a new assay for drug testing in a human context, but their validity
      particularly for the evaluation of inotropic drug effects remains unclear. In
      this blinded analysis, we compared the effects of 10 indicator compounds with
      known inotropic effects in electrically stimulated (1.5 Hz) hiPSC-CM-derived 3
      dimensional engineered heart tissue (EHT) and human atrial trabeculae (hAT).
      Human EHTs were prepared from iCell hiPSC-CM, hAT obtained at routine heart
      surgery. Mean intra-batch variation coefficient in baseline force measurement was
      17% for EHT and 49% for hAT. The PDE-inhibitor milrinone did not affect EHT
      contraction force, but increased force in hAT. Citalopram (selective serotonin
      reuptake inhibitor), nifedipine (LTCC-blocker) and lidocaine (Na+ channel
      blocker) had negative inotropic effects on EHT and hAT. Formoterol (beta-2
      agonist) had positive lusitropic but no inotropic effect in EHT, and positive
      clinotropic, lusitropic, and inotropic effects in hAT. Tacrolimus (calcineurin
      inhibitor) had a negative inotropic effect in EHTs, but no effect in hAT. Digoxin
      (Na+-K+-ATPase-inhibitor) showed a positive inotropic effect only in EHTs, but no
      effect in hAT probably due to short incubation time. Ryanodine (ryanodine
      receptor-inhibitor) reduced contraction force in both models. Rolipram and
      acetylsalicylic acid showed noninterpretable results in hAT. Contraction
      amplitude and kinetics were more stable over time and less variable in hiPSC-EHTs
      than hAT. HiPSC-EHT faithfully detected cAMP-dependent and -independent positive
      and negative inotropic effects, but limited beta-2 adrenergic or PDE3 effects,
      compatible with an immature CM phenotype.

PMID- 28453743
TI  - Targeted next-generation sequencing of pediatric neuro-oncology patients improves
      diagnosis, identifies pathogenic germline mutations, and directs targeted
      therapy.
AB  - Background: Molecular profiling is revolutionizing cancer diagnostics and leading
      to personalized therapeutic approaches. Herein we describe our clinical
      experience performing targeted sequencing for 31 pediatric neuro-oncology
      patients. Methods: We sequenced 510 cancer-associated genes from tumor and
      peripheral blood to identify germline and somatic mutations, structural variants,
      and copy number changes. Results: Genomic profiling was performed on 31 patients
      with tumors including 11 high-grade gliomas, 8 medulloblastomas, 6 low-grade
      gliomas, 1 embryonal tumor with multilayered rosettes, 1 pineoblastoma, 1 uveal
      ganglioneuroma, 1 choroid plexus carcinoma, 1 chordoma, and 1 high-grade
      neuroepithelial tumor. In 25 cases (81%), results impacted patient management by:
      (i) clarifying diagnosis, (ii) identifying pathogenic germline mutations, or
      (iii) detecting potentially targetable alterations. The pathologic diagnosis was
      amended after genomic profiling for 6 patients (19%), including a high-grade
      glioma to pilocytic astrocytoma, medulloblastoma to pineoblastoma, ependymoma to
      high-grade glioma, and medulloblastoma to CNS high-grade neuroepithelial tumor
      with BCOR alteration. Multiple patients had pathogenic germline mutations, many
      of which were previously unsuspected. Potentially targetable alterations were
      identified in 19 patients (61%). Additionally, novel likely pathogenic
      alterations were identified in 3 cases: an in-frame RAF1 fusion in a BRAF wild
      type pleomorphic xanthoastrocytoma, an inactivating ASXL1 mutation in a histone
      H3 wild-type diffuse pontine glioma, and an in-frame deletion within exon 2 of
      MAP2K1 in a low-grade astrocytic neoplasm. Conclusions: Our experience
      demonstrates the significant impact of molecular profiling on diagnosis and
      treatment of pediatric brain tumors and confirms its feasibility for use at the
      time of diagnosis or recurrence.

PMID- 28453744
TI  - Significance of low mTORC1 activity in defining the characteristics of brain
      tumor stem cells.
AB  - Background: The significance of mammalian target of rapamycin complex 1 (mTORC1)
      activity in the maintenance of cancer stem cells (CSCs) remains controversial.
      Previous findings showed that mTORC1 activation depleted the population of
      leukemia stem cells in leukemia, while maintaining the stemness in pancreatic
      CSCs. The purpose of this study was to examine the currently unknown role and
      significance of mTORC1 activity in brain tumor stem cells (BTSCs). Methods: Basal
      mTORC1 activity and its kinetics were investigated in BTSC clones isolated from
      patients with glioblastoma and their differentiated progenies (DIFFs). The
      effects of nutrient deprivation and the mTORC1 inhibitors on cell proliferation
      were compared between the BTSCs and DIFFs. Tissue sections from patients with
      brain gliomas were examined for expression of BTSC markers and mTORC1 activity by
      immunohistochemistry. Results: BTSCs presented lower basal mTORC1 activity under
      each culture condition tested and a more rapid decline of mTORC1 activity after
      nutrient deprivation than observed in DIFFs. The self-renewal capacity of BTSCs
      was unaffected by mTORC1 inhibition, whereas it effectively suppressed DIFF
      proliferation. In agreement, immunohistochemical staining of glioma tissues
      revealed low mTORC1 activity in tumor cells positive for BTSC markers. In in
      vitro culture, BTSCs exhibited resistance to the antitumor agent temozolomide.
      Conclusions: Our findings indicated the importance of low mTORC1 activity in
      maintaining the undifferentiated state of BTSCs, implicating the relevance of
      manipulating mTORC1 activity when developing future strategies that target BTSCs.

PMID- 28453745
TI  - Percentage of mesenchymal stem cells in high-grade glioma tumor samples
      correlates with patient survival.
AB  - Background: Human mesenchymal stem cells (hMSCs) have been shown to reside as
      stromal cells in human gliomas as glioma-associated hMSCs (GA-hMSCs), but their
      biological role remains unclear. Because recent evidence indicates that GA-hMSCs
      drive tumor cell proliferation and stemness, we hypothesized that a higher
      percentage of GA-hMSCs in tumors predicts poor patient prognosis. Method: We
      determined the percentage of cells coexpressing GA-hMSC markers
      CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and
      analyzed the association between this percentage and overall survival (OS) in 3
      independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9),
      cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome
      Atlas (TCGA) database. Results: In all cohorts, patient OS correlated with the
      percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with
      tumors with a low percentage of triple-positive cells was 46 months, and for
      tumors with a high percentage of triple-positive cells, it was 12 months (hazard
      ratio [HR] = 0.24; 95% CI: 0.02-0.5, P = .02). For cohort 2, the median OS of
      patients with tumors with a low percentage of GA-hMSCs was 66 months, and for
      tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P =
      .04). In the database of TCGA, the median OS times in patients with high and low
      coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4;
      95% CI: 0.1-0.88; P = .04), respectively. Conclusions: The percentage of GA-MSCs
      inversely correlates with OS, suggesting a role for GA-MSCs in promoting
      aggressive behavior of gliomas.

PMID- 28453746
TI  - Activation of CECR1 in M2-like TAMs promotes paracrine stimulation-mediated glial
      tumor progression.
AB  - Background: The majority of glioma-associated microglia/macrophages have been
      identified as M2-type macrophages with immune suppressive and tumor supportive
      action. Recently, the extracellular adenosine deaminase protein Cat Eye Syndrome
      Critical Region Protein 1 (CECR1) was shown to regulate macrophage maturation. In
      this study, we investigate the role of CECR1 in the regulation of the glioma
      associated macrophage response. Methods: Expression of CECR1 was assessed in
      human glioma samples. CECR1-mediated macrophage response was studied in vitro,
      using donor derived CD14+ monocytes and the THP-1 monocytic cell line. The
      response of the human glioma cell line U87 to conditioned medium of macrophages
      preconditioned with recombinant human CECR1 or CECR1 silencing was also assessed.
      Results: CECR1 was strongly expressed in high-grade gliomas (P < .001) and
      correlated positively with the M2 phenotype markers in tumor-associated
      microglia/macrophages (TAMs) (overall, P < .05). In vitro studies confirmed the
      presence of a significantly higher level of CECR1 expression in M2-like
      macrophages exposed to U87 conditioned medium (P < .001). CECR1 knockdown or
      stimulation of macrophages affected differentiation toward the M2-like phenotype.
      Stimulation of U87 cells with conditioned medium of CECR1 knockdown or stimulated
      macrophages affected tumor cell proliferation and migration, coinciding with
      altered intracellular signaling of mitogen-activated protein kinase (MAPK). In
      glioma tissue samples, CECR1 expression correlated with Ki67 and MAPK signaling
      protein. Conclusions: CECR1 is a potent regulator of TAM polarization and is
      consistently highly expressed by M2-type TAMs, particularly in high-grade glioma.
      Paracrine effects induced by CECR1 in M2-like TAMs activate MAPK signaling and
      stimulate the proliferation and migration of glioma cells.

PMID- 28453748
TI  - Incidence of pseudoprogression in low-grade gliomas treated with radiotherapy.
AB  - Background: As the incidence of pseudo-progressive disease (psPD), or
      pseudoprogression, in low-grade glioma (LGG) is unknown, we retrospectively
      investigated this phenomenon in a cohort of LGG patients given radiotherapy (RT).
      Methods: All MRI scans and clinical data from patients with histologically proven
      LGG treated with radiation between 2000 and 2011 were reviewed. PsPD was scored
      when a new enhancing lesion occurred after RT and subsequently disappeared or
      remained stable for at least a year without therapy, including dexamethasone.
      Results: Sixty-three out of 71 patients who received RT for LGG were deemed
      eligible for evaluation of psPD. The median follow-up was 5 years (range 1-10 y).
      PsPD was seen in 13 patients (20.6%). PsPD occurred after a median of 12 months
      with a range of 3-78 months. The median duration of psPD was 6 months, with a
      range of 2-26 months and always occurred within the RT high dose fields of at
      least 45 Gy. The area of the enhancement at the time of psPD was significantly
      smaller compared with the area of enhancement during "true" progression (median
      size 54mm2 [range 12-340mm2] vs 270mm2 [range 30-3420mm2], respectively; P =
      .009). Conclusions: PsPD occurs frequently in LGG patients receiving RT. This
      supports the policy to postpone a new line of treatment until progression is
      evident, especially when patients have small contrast enhancing lesions within
      the RT field.

PMID- 28453747
TI  - Natural course and prognosis of anaplastic gangliogliomas: a multicenter
      retrospective study of 43 cases from the French Brain Tumor Database.
AB  - Background: Anaplastic gangliogliomas (GGGs) are rare tumors whose natural
      history is poorly documented. We aimed to define their clinical and imaging
      features and to identify prognostic factors. Methods: Consecutive cases of
      anaplastic GGGs in adults prospectively entered into the French Brain Tumor
      Database between March 2004 and April 2014 were screened. After diagnosis was
      confirmed by pathological review, clinical, imaging, therapeutic, and outcome
      data were collected retrospectively. Results: Forty-three patients with
      anaplastic GGG (median age, 49.4 y) from 18 centers were included. Presenting
      symptoms were neurological deficit (37.2%), epileptic seizure (37.2%), or
      increased intracranial pressure (25.6%). Typical imaging findings were unifocal
      location (94.7%), contrast enhancement (88.1%), central necrosis (43.2%), and
      mass effect (47.6%). Therapeutic strategy included surgical resection (95.3%),
      adjuvant radiochemotherapy (48.8%), or radiotherapy alone (27.9%). Median
      progression-free survival (PFS) and overall survival (OS) were 8.0 and 24.7
      months, respectively. Three- and 5-year tumor recurrence rates were 69% and 100%,
      respectively. The 5-year survival rate was 24.9%. Considering unadjusted
      significant prognostic factors, tumor midline crossing and frontal location were
      associated with shorter OS. Temporal and parietal locations were associated with
      longer and shorter PFS, respectively. None of these factors remained
      statistically significant in multivariate analysis. Conclusions: We report a
      large series providing clinical, imaging, therapeutic, and prognostic features of
      adult patients treated for an intracerebral anaplastic GGG. Our results show that
      pathological diagnosis is difficult, that survivals are only slightly better than
      for glioblastomas, and that complete surgical resection followed with adjuvant
      chemoradiotherapy offers longer survival.

PMID- 28453750
TI  - NovoTTF: where to go from here?

PMID- 28453749
TI  - An independently validated nomogram for individualized estimation of survival
      among patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and
      0825.
AB  - Background: Glioblastoma (GBM) is the most common primary malignant brain tumor.
      Nomograms are often used for individualized estimation of prognosis. This study
      aimed to build and independently validate a nomogram to estimate individualized
      survival probabilities for patients with newly diagnosed GBM, using data from 2
      independent NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials.
      Methods: This analysis included information on 799 (RTOG 0525) and 555 (RTOG
      0825) eligible and randomized patients with newly diagnosed GBM and contained the
      following variables: age at diagnosis, race, gender, Karnofsky performance status
      (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT)
      methylation status, and survival (in months). Survival was assessed using Cox
      proportional hazards regression, random survival forests, and recursive
      partitioning analysis, with adjustment for known prognostic factors. The models
      were developed using the 0525 data and were independently validated using the
      0825 data. Models were internally validated using 10-fold cross-validation, and
      individually predicted 6-, 12-, and 24-month survival probabilities were
      generated to measure the predictive accuracy and calibration against the actual
      survival status. Results: A final nomogram was built using the Cox proportional
      hazards model. Factors that increased the probability of shorter survival
      included greater age at diagnosis, male gender, lower KPS, not having total
      resection, and unmethylated MGMT status. Conclusions: A nomogram that assesses
      individualized survival probabilities (6-, 12-, and 24-mo) for patients with
      newly diagnosed GBM could be useful to health care providers for counseling
      patients regarding treatment decisions and optimizing therapeutic approaches.
      Free software for implementing this nomogram is provided:
      http://cancer4.case.edu/rCalculator/rCalculator.html.

PMID- 28453752
TI  - NANO, a practical scale for neurologic assessments in patients with brain tumors?

PMID- 28453751
TI  - The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess
      neurologic function for integration into the Response Assessment in Neuro
      Oncology (RANO) criteria.
AB  - Background: The Macdonald criteria and the Response Assessment in Neuro-Oncology
      (RANO) criteria define radiologic parameters to classify therapeutic outcome
      among patients with malignant glioma and specify that clinical status must be
      incorporated and prioritized for overall assessment. But neither provides
      specific parameters to do so. We hypothesized that a standardized metric to
      measure neurologic function will permit more effective overall response
      assessment in neuro-oncology. Methods: An international group of physicians
      including neurologists, medical oncologists, radiation oncologists, and
      neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment
      in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of
      neurologic function evaluable during a routine office examination. The scale was
      subsequently tested in a multicenter study to determine its overall reliability,
      inter-observer variability, and feasibility. Results: The NANO scale is a
      quantifiable evaluation of 9 relevant neurologic domains based on direct
      observation and testing conducted during routine office visits. The score defines
      overall response criteria. A prospective, multinational study noted a >90% inter
      observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to
      almost perfect agreement), and a median assessment time of 4 minutes
      (interquartile range, 3-5). Conclusion: The NANO scale provides an objective
      clinician-reported outcome of neurologic function with high inter-observer
      agreement. It is designed to combine with radiographic assessment to provide an
      overall assessment of outcome for neuro-oncology patients in clinical trials and
      in daily practice. Furthermore, it complements existing patient-reported outcomes
      and cognition testing to combine for a global clinical outcome assessment of well
      being among brain tumor patients.

PMID- 28453753
TI  - Effects of commercial organic acid blends on male broilers challenged with E.
      coli K88: Performance, microbiology, intestinal morphology, and immune response.
AB  - This study assessed the effects of 3 commercial organic acid (OA) preparations on
      growth performance, intestinal morphology, cecal microbiology, and immunity of
      Escherichia coli K88-challenged (ETEC) broiler chickens. One thousand one-day-old
      male broiler chickens were divided into 8 treatments of 5 replicate pens:
      Negative control (NC) birds received a basal diet (BD) and were not challenged
      with ETEC; positive control (PC) birds fed the BD and challenged with ETEC; BD +
      0.2% (S1) or 0.4% (S2) of an OA mixture (Salkil) from one to 35 d; BD + 0.1,
      0.075, and 0.05% (O1) of another OA mixture (Optimax) in the starter (one to 10
      d), grower (11 to 24 d), and finisher (25 to 35 d) diets, respectively, or 0.1%
      (O2) from one to 35 d; BD + 0.07, 0.05, and 0.05% (P1) or 0.1, 0.07, and 0.05%
      (P2) of a further OA mixture (pHorce) in the starter, grower, and finisher diets,
      respectively. All groups (not NC) were challenged with one mL of ETEC (1 * 108
      cfu/mL) at 7 d of age. The 3 OA mixtures are commercial formic and propionic acid
      preparations. Birds challenged with ETEC (PC) had reduced (P < 0.05) growth
      performance, ileal morphological parameters (not crypt depth, which was
      increased), cecal lactobacilli, and immune responses, and increased cecal E. coli
      compared with unchallenged, NC birds. The addition of OA to the diets of ETEC
      challenged birds (S1-P2) either numerically or significantly (P < 0.05) improved
      growth performance, ileal morphology and immune responses, increased cecal
      lactobacilli, and reduced cecal E. coli. For most OA additions, the assessed
      parameters were generally enhanced to equivalence to NC birds. The results
      suggest that dietary OA supplementation can enhance the growth performance, ileal
      morphology, cecal microbiota, and immunity of ETEC-challenged broilers to an
      extent that, under such circumstances, the formulations used in this study
      provided similar performance and assessed parameters as non-challenged birds.

PMID- 28453754
TI  - Once- Versus Twice-daily Mesalazine to Induce Remission in Paediatric Ulcerative
      Colitis: A Randomised Controlled Trial.
AB  - Background: Trials in adults suggested that, in ulcerative colitis [UC], once
      daily [OD] dosing of 5-ASA [5-amino salicylic acid] may be as or more effective
      than twice-daily [BD] dosing. In this induction of remission, investigator
      blinded, randomised controlled-trial, we aimed to compare effectiveness and
      safety of once- versus twice-daily mesalazine in paediatric UC. Methods:
      Children, aged 4-18 years with a PUCAI [Paediatric Ulcerative Colitis Activity
      Index] of 10-55 points at inclusion, were randomised in blocks of six with
      blinded allocation to OD or BD mesalazine, using a weight-based dosing table. The
      primary outcome was mean PUCAI score at Week 6. Results: A total of 83/86
      randomised children were eligible and analysed: 43 in the OD group and 40 in the
      BD group (mean age 14 +/- 2.7 years, 43 [52%] males, 51 [62%] extensive colitis).
      The groups did not differ with regard to disease activity or any other parameter
      at baseline. There was no difference in median PUCAI score between the OD group
      and BD group at Week 6: 15 ( interquartile range [IQR] 5-40) versus 10 [0-40]; p
      = 0.48]. Response was seen in 25 [60%] OD versus 25 [63%] BD dosing [p = 0.78].
      Proportion of children in remission [PUCAI < 10] at Week 6 was 13 [30%] OD versus
      16 [40%] BD; p = 0.35]. Most adverse events were related to disease aggravation;
      the rates of serious adverse events were similar [p > 0.2]. Conclusions: In this
      first randomised controlled trial in children, no differences were found between
      OD and BD dosing for any clinical outcome. Remission was achieved in 35% of
      children treated with mesalazine for active UC.

PMID- 28453755
TI  - Association of Induction Infliximab Levels With Clinical Response in Perianal
      Crohn's Disease.
AB  - Background: The association of infliximab [IFX] trough levels with clinical and
      endoscopic outcomes in inflammatory bowel disease is well established. However,
      there is scarce data regarding the association of perianal fistula response with
      IFX. The aim of this study was to establish whether early induction infliximab
      levels and anti-infliximab antibodies [ATIs] are associated with perianal fistula
      response. Methods: Consecutive CD patients with perianal fistulae that were
      treated with IFX between 2008 and 2016 were included in the study. Response was
      defined as cessation or significant improvement of fistula drainage. Patients
      with unavailable IFX level or ATI measurements and/or missing clinical follow-up
      at Week 14 were excluded. Results: A total of 36 patients with perianal fistulae
      were included; 25/36 [69.4%] responded to treatment by Week 14. The median
      induction IFX levels at Weeks 2, 6 and 14 in the responders group at Week 14 were
      higher compared with those of the non-responders group [20/5.6 ug/mL, P = 0.0001;
      13.3/2.55 ug/mL P = 0.0001; 4.1/0.14 ug/mL, P = 0.01]. On multivariate analysis,
      IFX leve at Weeks 2 and 6 were significantly associated with fistula response at
      Weeks 14 and 30. IFX drug levels of 9.25 ug/mL at Week 2 and 7.25 ug/mL at Week 6
      were the best predictors of fistula response. Conclusion: High IFX trough levels
      during induction are associated with favorable fistula response to anti-TNF
      treatment. If validated in a larger prospective study, our findings may help
      guide anti-TNF treatment in patients with perianal CD, and suggest serum level
      guided treatment escalation in non-responders or prompt changing of biologic
      treatment in non-responders.

PMID- 28453756
TI  - Malignancies in Patients with Inflammatory Bowel Disease: Results from 20 Years
      of Follow-up in the IBSEN Study.
AB  - Background and Aims: Whether patients with inflammatory bowel diseases [IBDs]
      have increased risk of developing cancer has been debated. The aims of the study
      were to determine the prevalence of intestinal/extraintestinal cancers in an IBD
      cohort 20 years after diagnosis and to assess whether these patients had an
      increased cancer-specific risk compared with a matched control population.
      Methods: Patients with ulcerative colitis [UC] and Crohn's disease [CD] diagnosed
      1990-1993 have been prospectively followed up for 20 years. Follow-up visits were
      carried out 1, 5, 10, and 20 years after inclusion. Data on all cancer cases,
      deaths, and causes of death were collected from the Cancer Registry of Norway and
      from the Norwegian Cause of Death Registry. Results: In all, 756 patients [519 UC
      and 237 CD] were diagnosed with IBD. Increased risk of cancer was seen in UC
      patients (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.08-1.81, p <
      0.01), but not in CD patients [HR = 1.23, 95% CI 0.80-2.03, p = 0.30]. Stratified
      by gender, our data revealed a statistically increased risk for all cancers only
      in male UC patients compared with the controls [HR = 1.51, 95% CI 1.08-2.11, p =
      0.017]. In both groups breast cancer was seen more often than expected.
      Conclusions: Male UC patients display an increased risk of development of
      colorectal cancer and, also all cancers combined, compared with the controls. In
      both UC and CD, standardized incidence ratio for breast cancer was increased.

PMID- 28453757
TI  - Incidence and Phenotype at Diagnosis of Very-early-onset Compared with Later
      onset Paediatric Inflammatory Bowel Disease: A Population-based Study [1988
      2011].
AB  - Background and Aims: Very-early-onset inflammatory bowel disease [VEO-IBD] is a
      form of IBD that is distinct from that of children with an older onset. We
      compared changes over time in the incidence and phenotype at diagnosis between
      two groups according to age at IBD diagnosis: VEO-IBD diagnosed before the age of
      6 years, and early-onset IBD [EO-IBD] diagnosed between 6 and 16 years of age.
      Methods: Data were obtained from a cohort enrolled in a prospective French
      population-based registry from 1988 to 2011. Results: Among the 1412 paediatric
      cases [< 17 years], 42 [3%] were VEO-IBD. In the VEO-IBD group, the incidence
      remained stable over the study period. In contrast, the incidence of EO-IBD
      increased from 4.4/105 in 1988-1990 to 9.5/105 in 2009-2011 [+116%; p < 10-4].
      Crohn's disease [CD] was the most common IBD, regardless of age, but ulcerative
      colitis [UC] and unclassified IBD were more common in VEO-IBD cases [40% vs 26%;
      p = 0.04]. VEO-IBD diagnosis was most often performed in hospital [69% vs 43%; p
      < 10-3]. Rectal bleeding and mucous stools were more common in patients with VEO
      IBD, whereas weight loss and abdominal pain were more frequent in those with EO
      IBD. Regarding CD, isolated colonic disease was more common in the VEO-IBD group
      [39% vs 14%; p = 0.003]. Conclusions: In this large population-based cohort, the
      incidence of VEO-IBD was low and stable from 1988 to 2011, with a specific
      clinical presentation. These results suggest a probable genetic origin for VEO
      IBD, whereas the increase in EO-IBD might be linked to environmental factors.

PMID- 28453758
TI  - Training Programs on Endoscopic Scoring Systems for Inflammatory Bowel Disease
      Lead to a Significant Increase in Interobserver Agreement Among Community
      Gastroenterologists.
AB  - Background and Aims: Endoscopic outcomes are increasingly used in clinical trials
      and in routine practice for inflammatory bowel disease [IBD] in order to reach
      more objective patient evaluations than possible using only clinical features.
      However, reproducibility of endoscopic scoring systems used to categorize
      endoscopic activity has been reported to be suboptimal. The aim of this study was
      to analyse the inter-rated agreement of non-dedicated gastroenterologists on IBD
      endoscopic scoring systems, and to explore the effects of a dedicated training
      programme on agreement. Methods: A total of 237 physicians attended training
      courses on IBD endoscopic scoring systems, and they independently scored a set of
      IBD endoscopic videos for ulcerative colitis [with Mayo endoscopic subscore],
      post-operative Crohn's disease [with Rutgeerts score] and luminal Crohn's disease
      (with the Simple Endoscopic Score for Crohn's Disease [SESCD] and Crohn's
      Endoscopic Index of Severity [CDEIS]). A second round of scoring was collected
      after discussion about determinants of discrepancy. Interobserver agreement was
      measured by means of the Fleiss' kappa [kappa] or intraclass correlation
      coefficient [ICC] as appropriate. Results: The inter-rater agreement increased
      from kappa 0.51 (95% confidence interval [95% CI] 0.48-0.55) to 0.76 [95% CI 0.72
      0.79] for the Mayo endoscopic subscore, and from 0.45 [95% CI 0.40-0.50] to 0.79
      [0.74-0.83] for the Rutgeerts score before and after the training programme,
      respectively, and both differences were significant [P < 0.0001]. The ICC was
      0.77 [95% CI 0.56-0.96] for SESCD and 0.76 [0.54- 0.96] for CDEIS, respectively,
      with only one measurement. Discussion: The basal inter-rater agreement of
      inexperienced gastroenterologists focused on IBD management is moderate; however,
      a dedicated training programme can significantly impact on inter-rater agreement,
      increasing it to levels expected among expert central reviewers.

PMID- 28453759
TI  - Randomised, Double-blind, Placebo-controlled Trial of CCR9-targeted Leukapheresis
      Treatment of Ulcerative Colitis Patients.
AB  - Background and Aims: Ulcerative colitis patients display increased numbers of
      circulating pro-inflammatory monocyte human leukocyte antigen-DR [HLA-DRhi]
      monocytes expressing high levels of the gut-homing C-C chemokine receptor 9
      [CCR9] and tumour necrosis factor [TNF]-alpha. The aim of this first-in-human,
      double-blind, randomised, placebo-controlled trial was to evaluate selective
      removal of circulating CCR9-expressing monocytes by leukapheresis in patients
      with moderate to severe ulcerative colitis, with regards to safety, tolerability,
      and immunological response. Methods: Patients with ulcerative colitis were
      treated every second day with leukapheresis during five sessions with a C-C
      chemokine ligand 25 [CCL25; CCR9 ligand] column or a placebo column. Results: No
      major safety concerns were raised and the procedure was well tolerated. Pro
      inflammatory HLA-DRhi cells decreased significantly in the active treatment group
      [p = 0.0391] whereas no statistically significant change was seen in the placebo
      group [p = 0.4688]. There was a significant decrease of HLA-DRhi monocytes in the
      active group compared with the placebo group when corrected for the imbalance in
      weight between the groups [p = 0.0105]. Mayo score decreased in the active group
      [p = 0.0156] whereas the change in the placebo group was not significant [p =
      0.1250]. Mayo score <= 3 was observed in five out of 14 patients [35.7%] in the
      active group compared with one out of eight [12.5%] receiving placebo. The number
      of responders in the active treatment group was eight out of 14 patients [57.1%],
      whereas in the corresponding placebo group three out of eight patients [37.5%]
      responded to placebo. A dose-response correlation was observed between the blood
      volume processed and clinical outcome. Conclusion: This clinical induction trial
      using CCL25-tailored leukapheresis demonstrates a safe and effective removal of
      activated monocytes with a clinical effect in patients with ulcerative colitis.

PMID- 28453760
TI  - Long-term Inflammation Transforms Intestinal Epithelial Cells of Colonic
      Organoids.
AB  - Background and Aims: Patients with ulcerative colitis [UC] are at an increased
      risk of developing colitis-associated cancer [CAC], suggesting that continuous
      inflammation in the colon promotes the transformation of colonic epithelial
      cells. However, the mechanisms underlying cell transformation in UC remain
      unknown. We therefore aimed to investigate the effect of long-term inflammation
      on intestinal epithelial cells [IECs] using organoid culture. Methods: IECs were
      isolated from mouse colon, and were cultured according to a method for a three
      dimensional [3D] organoid culture. To mimic chronic inflammation, a mixture of
      cytokines and bacterial components were added to the medium for over a year. Cell
      signal intensity was assessed by 3D immunofluorescence. Cell transformation was
      assessed by microarray with gene set enrichment analysis. Results: Stimulation
      with cytokines resulted in a significant induction of target genes for the
      nuclear factor [NF]-kappaB pathway in colonic organoids. Following 60 weeks of
      continuous stimulation, cell differentiation was suppressed. Continuous
      stimulation also resulted in significant amplification of NF-kappaB signalling.
      Amplified NF-kappaB signalling by long-term stimulation remained in colonic
      organoids even 11 weeks after the removal of all cytokines. Some genes were
      specifically upregulated only in colonic organoids after the removal all
      cytokines following long-term stimulation. Conclusions: Colonic organoids
      stimulated with cytokines for a prolonged period were established as in vitro
      model to assess long-term epithelial responses to inflammatory cytokines. Chronic
      inflammation led to sustained NF-kappaB signalling activation in colonic
      organoids, resulting in cell transformation that might be related to the
      carcinogenesis of CAC in UC.

PMID- 28453761
TI  - The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in
      Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.
AB  - Background and Aims: Inflammatory bowel disease [IBD] is a chronic disease which
      affects up to 0.5% of the population. Various extraintestinal manifestations
      occur, among which are rheumatic manifestations, grouped together under the name
      spondyloarthritis. The objective of this systematic review and meta-analysis was
      to give a systematic overview of the prevalence and incidence of
      spondyloarthritis in patients with inflammatory bowel disease. Methods: We
      systematically searched Embase, Pubmed, OvidSP, Scopus, and Web-of-Science
      databases from inception to August 2016. All articles that addressed the
      prevalence or incidence of the different features of spondyloarthritis in adult
      inflammatory bowel disease patients were included. Methodological quality was
      assessed using a modified quality assessment tool developed for prevalence
      studies. Results: A total of 71 studies were included, reporting on the
      prevalence of sacroiliitis, ankylosing spondylitis, arthritis, enthesitis, and
      dactylitis. Pooled prevalences were calculated for sacroiliitis (10%; 95%
      confidence interval [CI] 8-12%), ankylosing spondylitis [3%; 95% CI 2-4%], and
      arthritis [13%; 95% CI 12-15%]. Geographical area, setting and use of different
      criteria contribute to the large heterogeneity. Few estimates were available for
      enthesitis [prevalence range from 1% to 54%] and dactylitis [prevalence range
      from 0% to 6%]. Only three incidence studies were identified, which report
      cumulative incidences from 5 to 30 years. Conclusions: Spondyloarthritis occurs
      in up to 13% of patients with IBD. Ankylosing spondylitis is the least common
      [3%] followed by sacroiliitis [10%] and peripheral arthritis [13%].

PMID- 28453762
TI  - Estimates of Disease Course in Inflammatory Bowel Disease Using Administrative
      Data: A Population-level Study.
AB  - Background and Aims: We sought develop a predictive model of disease course in
      inflammatory bowel disease [IBD] using health care utilization measures from
      administrative health data, and to apply this model to estimate disease course at
      a population level over time. Methods: Study participants were IBD patients who
      were prospectively followed for a 1-year period between 2009 and 2010 in a
      Canadian clinic setting to assess their IBD disease course [i.e. remission, mild,
      moderate, severe]. Clinic data were linked with population-based administrative
      health data. A multivariable partial proportional odds model tested health care
      utilization measures that discriminated disease course groups. The model was
      applied to project the distribution of disease course for the Manitoba IBD
      population for 1995-2013. Results: There were 407 participants (54.3% females,
      64.4% Crohn's disease [CD]) with mean age at diagnosis of 29.8 years [SD 14.9].
      Forty-one per cent of participants were clinically in remission, while 14.0% had
      severe IBD. Mild, moderate or severe disease was associated with three or more
      gastroenterologist visits (odds ratio [OR] = 3.33, 95% confidence interval [CI]:
      2.03-5.54) or three or more general practitioner visits [OR = 2.97, 95% CI: 1.44
      6.37] with an IBD diagnosis and >=1 radiology test [OR = 2.22, 95% CI: 1.31
      3.80]. The percentages of the Manitoba IBD population in remission rose steadily
      from 1995 to 2013 [43.6 to 59.9%], while the percentages of individuals with
      mild, moderate or severe disease declined. Conclusion: This study demonstrated
      that health care utilization measures from administrative data can be used to
      predict disease course in the IBD population.

PMID- 28453763
TI  - Development of the Harvey-Bradshaw Index-pro (HBI-PRO) Score to Assess Endoscopic
      Disease Activity in Crohn's Disease.
AB  - Background: There is a need for better, less-invasive disease activity indices
      that provide a representative assessment of endoscopic disease activity. We
      developed a new clinical score that incorporates the Harvey-Bradshaw index [HBI]
      with modified patient-reported outcomes [PROp] and physician [clinician]-reported
      outcomes [PROc] and assessed its ability to measure endosopic disease activity in
      ileocolonic Crohn's disease [CD]. Methods: A cohort of 88 CD patients undergoing
      colonoscopy was accrued in a prospective fashion. In total, 48 of the subjects
      were CD cases and 40 had already undergone a post-operative ileocolonic resection
      [post-op CD]. Each patient underwent multiple, endoscopist-blinded assessments
      including: HBI score, a PROp question asking for patient perception of disease
      activity status, a PROc question for clinician perception of disease activity
      status and C-reactive protein [CRP]. Active endoscopic disease was defined as
      Simple Endoscopic Score for CD [SES-CD] >= 3 for CD subjects and Rutgeerts score
      > i1 for post-op CD subjects. Results: Clinical remission as defined by the HBI
      did not accurately reflect endoscopic remission as defined by the SES-CD (area
      under the curve [AUC] = 0.54). Combining the HBI with PROp and PROc scores and
      then further adding CRP significantly improved the correlation with SES-CD [AUC =
      0.78 and AUC = 0.88, respectively, p < 0.00001]. In post-op CD, HBI-defined
      remission also performed poorly against endoscopic remission defined by the
      Rutgeerts score [AUC = 0.52]. Combining HBI with PROp and the PROc scores and
      then further adding CRP did not significantly improve the model [AUC = 0.65 and
      AUC = 0.61, respectively, p = NS]. Conclusion: In CD, the HBI correlates poorly
      with endoscopic disease activity. However, the HBI-PRO score, which incorporated
      PROp, PROc, CRP and HBI, significantly improved its ability to predict endoscopic
      activity in ileocolonic CD without prior surgery.

PMID- 28453764
TI  - Response to 'Preoperative Vedolizumab and Postoperative Outcomes in Inflammatory
      Bowel Disease: Does Smoke Always Mean Fire?'

PMID- 28453765
TI  - CCL20 Is Negatively Regulated by TGF-beta1 in Intestinal Epithelial Cells and
      Reduced in Crohn's Disease Patients With a Successful Response to Mongersen, a
      Smad7 Antisense Oligonucleotide.
AB  - Background and Aims: The chemokine CCL20 is over-produced in epithelium of
      Crohn's disease [CD] patients and contributes to recruiting immune cells to
      inflamed gut. Tumour necrosis factor-alpha [TNF-alpha] is a powerful inducer of
      CCL20 in intestinal epithelial cells. In CD, high levels of Smad7 block the
      activity of transforming growth factor-beta1 [TGF-beta1], a negative regulator of
      TNF signalling. We investigated whether intestinal epithelial cell-derived CCL20
      is negatively regulated by TGF-beta1 and whether Smad7 knock-down reduces CCL20
      in CD. Methods: CCL20 was evaluated in NCM460, a normal colonic epithelial cell
      line, stimulated with TGF-beta1 and TNF-alpha, and in Smad7 over-expressing
      NCM460 cells. CCL20 and Smad7 expression were assessed in sections of CD
      intestinal specimens by immunochemistry, and in CD colonic explants treated with
      mongersen, a Smad7 antisense oligonucleotide. CCL20 was examined in serum samples
      taken from 95 of 166 active CD patients receiving mongersen or placebo for 2
      weeks and participating in a phase II, multicentre, double-blind, placebo
      controlled study. Results: CCL20 expression was increased by TNF-alpha, and this
      effect was inhibited by TGF-beta1 in NCM460 cells, but not in Smad7 over
      expressing NCM460 cells. In CD, epithelium CCL20 and Smad7 co-localised, and
      treatment of CD explants with mongersen reduced CCL20 production. During follow
      up, in responders to mongersen, serum CCL20 levels significantly decreased,
      whereas patients without response/remission to mongersen and placebo patients did
      not have change in CCL20. Conclusions: TGF-beta1 reduces intestinal epithelial
      cell-derived CCL20 production, an effect abrogated by Smad7. CD patients
      responding to mongersen demonstrated a reduction in serum CCL20.

PMID- 28453766
TI  - Comparable Immune Function Inhibition by the Infliximab Biosimilar CT-P13:
      Implications for Treatment of Inflammatory Bowel Disease.
AB  - Background and Aims: CT-P13 is the first biosimilar monoclonal antibody to
      infliximab, and was recently approved in the European Union, Japan, Korea, and
      USA for all six indications of infliximab. However, studies directly assessing
      the biologic activity of CT-P13 versus inflximab in the context of inflammatory
      bowel disease [IBD] are still scanty. In the present study, we aimed to compare
      the biological activities of CT-P13 and infliximab with specific focus on
      intestinal cells so as to gain insight into the potential biosimilarity of these
      two agents for treatment of IBD. Methods: CT-P13 and infliximab were investigated
      and compared by in vitro experiments for their neutralisation ability of soluble
      tumour necrosis factor alpha [sTNFalpha] and membrane-bound tumour necrosis
      factor alpha [mTNFalpha], suppression of cytokine release by reverse signalling,
      induction of regulatory macrophages and wound healing, and antibody-dependent
      cell cytotoxicity [ADCC]. Results: CT-P13 showed similar biological activities to
      infliximab as gauged by neutralisation of soluble TNFalpha, as well as blockade
      of apoptosis and suppression of pro-inflammatory cytokines in intestinal Caco-2
      cells. Infliximab and CT-P13 equally induced apoptosis and outside-to-inside
      signals through transmembrane TNFalpha [tmTNFalpha]. Moreover, regulatory
      macrophage induction and ensuing wound healing were similarly exerted by CT-P13
      and infliximab. However, neither CT-P13 nor infliximab exerted any significant
      ADCC of ex vivo-stimulated peripheral blood monocytes or lamina propria
      mononuclear cells from IBD patients. Conclusions: These findings indicate that CT
      P13 and infliximab exert highly similar biological activities in intestinal
      cells, and further support a mechanistic comparability of these two drugs in the
      treatment of IBD.

PMID- 28453767
TI  - The Pattern of Underlying Cause of Death in Patients with Inflammatory Bowel
      Disease in England: A Record Linkage Study.
AB  - Background and Aims: Numerous studies have established that mortality risk in
      inflammatory bowel disease [IBD] patients is higher than in the general
      population, but the causes of death have seldom been examined. We aimed to
      describe causes of death in IBD. Methods: A matched cohort study using UK general
      practice data from Clinical Practice Research Datalink linked to death
      registration records. We described the distribution of causes of death among IBD
      patients by age at death and time since IBD diagnosis. We estimated age-specific
      mortality rates and hazard ratios of death in multivariable Cox proportional
      hazards models. Results: 20293 IBD patients were matched to 83261 non IBD
      patients. The mortality rate was 40% higher in IBD patients [2005 deaths] than in
      non IBD patients [6024 deaths] (adjusted overall hazard ratio: = 1.4, 95%
      confidence interval [CI]: = 1.4-1.5], with greater risk of death in Crohn's
      disease [hazard ratio: = 1.6, 1.5-1.7] than in ulcerative colitis [1.3, 1.3-1.4].
      Causes attributable to IBD constituted 3.7% of all deaths in ulcerative colitis
      and 8.3% in Crohn's disease. Among IBD patients, death was less likely to be due
      to circulatory, respiratory or neoplastic diseases than among non IBD patients.
      In both IBD and non IBD patients all these causes became more clinically
      important with advancing age, with the commonest neoplastic cause of death being
      lung cancer rather than gastrointestinal cancers. Conclusions: IBD patients have
      an additional risk of death. Most IBD patients die of circulatory or respiratory
      causes, and the contribution to mortality from long-term complications of IBD is
      clinically less important.

PMID- 28453769
TI  - Preoperative Vedolizumab and Postoperative Outcomes in Inflammatory Bowel
      Disease: Does Smoke Always Mean Fire?

PMID- 28453768
TI  - alphaEbeta7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T
      Lymphocytes in Ulcerative Colitis.
AB  - Background and Aims: The alphaEbeta7 integrin is crucial for retention of T
      lymphocytes at mucosal surfaces through its interaction with E-cadherin.
      Pathogenic or protective functions of these cells during human intestinal
      inflammation, such as ulcerative colitis [UC], have not previously been defined,
      with understanding largely derived from animal model data. Defining this
      phenotype in human samples is important for understanding UC pathogenesis and is
      of translational importance for therapeutic targeting of alphaEbeta7-E-cadherin
      interactions. Methods: alphaEbeta7+ and alphaEbeta7- colonic T cell localization,
      inflammatory cytokine production and expression of regulatory T cell-associated
      markers were evaluated in cohorts of control subjects and patients with active UC
      by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell
      populations. Results: CD4+alphaEbeta7+ T lymphocytes from both healthy controls
      and UC patients had lower expression of regulatory T cell-associated genes,
      including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+alphaEbeta7- T
      lymphocytes. In UC, CD4+alphaEbeta7+ lymphocytes expressed higher levels of
      IFNgamma and TNFalpha in comparison with CD4+alphaEbeta7- lymphocytes.
      Additionally the CD4+alphaEbeta7+ subset was enriched for Th17 cells and the
      recently described Th17/Th1 subset co-expressing both IL-17A and IFNgamma, both
      of which were found at higher frequencies in UC compared to control. Conclusion:
      alphaEbeta7 integrin expression on human colonic CD4+ T cells was associated with
      increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with
      reduced expression of regulatory T cell-associated markers. These data suggest
      colonic CD4+alphaEbeta7+ T cells are pro-inflammatory and may play a role in UC
      pathobiology.

PMID- 28453770
TI  - Mitochondrial Genome Evolution and a Novel RNA Editing System in Deep-Branching
      Heteroloboseids.
AB  - Discoba (Excavata) is an evolutionarily important group of eukaryotes that
      includes Jakobida, with the most bacterial-like mitochondrial genomes known, and
      Euglenozoa, many of which have extensively fragmented mitochondrial genomes.
      However, little is known about the mitochondrial genomes of Heterolobosea, the
      third main group of Discoba. Here, we studied two heteroloboseids-an undescribed
      amoeba "BB2" and Pharyngomonas kirbyi. Phylogenomic analysis revealed that they
      form a clade that is a sister group to all other Heterolobosea. We characterized
      the mitochondrial genomes of BB2 and P. kirbyi, which encoded 44 and 48 putative
      protein-coding genes respectively. Their gene contents were similar to that of
      Naegleria. In BB2, mitochondrially encoded RNAs were heavily edited, with ~500
      mononucleotide insertion events, mostly guanosines. These insertions always have
      the same identity as an adjacent nucleotide. Editing occurs in all ribosomal RNAs
      and protein-coding transcripts except one, and half of the transfer RNAs.
      Analysis of Illumina deep-sequencing data suggested that this RNA editing is very
      accurate and efficient, and most likely co-transcriptional. The dissimilarity of
      this editing process to other RNA editing phenomena in discobids, as well as its
      apparent absence in P. kirbyi, suggest that this remarkably extensive system of
      insertional editing evolved independently in the BB2 lineage, after its
      divergence from the P. kirbyi lineage.

PMID- 28453771
TI  - From the Cover: Interplay Between IFN-gamma and IL-6 Impacts the Inflammatory
      Response and Expression of Interferon-Regulated Genes in Environmental-Induced
      Autoimmunity.
AB  - IFN-gamma has been found to be robustly important to disease pathogenesis in both
      idiopathic and induced models of murine lupus. In transgenic mice, over
      production of IFN-gamma in the skin results in an inflammatory response and
      autoimmunity. This suggests that localized exposure to environmental factors that
      induce autoimmunity may be associated with expression of an IFN-gamma-dependent
      inflammatory response. Using murine mercury-induced autoimmunity (mHgIA), the
      severity of inflammation and proinflammatory cytokine expression, including the
      cellular source of IFN-gamma, were assessed at the site of subcutaneous exposure
      and in secondary lymphoid organs. Exposure induced a localized chronic
      inflammation comprising both innate and adaptive immune cells but only CD8+ T and
      NK cells were reduced in the absence of IFN-gamma. IFN-gamma+ cells began to
      appear as early as day 1 and comprised both resident (gammadelta T) and
      infiltrating cells (CD8+ T, NKT, CD11c+). The requirements for inflammation were
      examined in mice deficient in genes required (Ifng, Il6) or not required (Casp1)
      for mHgIA. None of these genes were essential for induction of inflammation,
      however IFN-gamma and IL-6 were required for exacerbation of other
      proinflammatory cytokines. Additionally, lack of IFN-gamma or IL-6 impacted
      expression of genes regulated by either IFN-gamma or type I IFN. Significantly,
      both IFN-gamma and IL-6 were required for increased expression of IRF-1 which
      regulates IFN stimulated genes and is required for mHgIA. Thus IRF-1 may be at
      the nexus of the interplay between IFN-gamma and IL-6 in exacerbating a
      xenobiotic-induced inflammatory response, regulation of interferon responsive
      genes and autoimmunity.

PMID- 28453772
TI  - Hepatic Hazard Assessment of Silver Nanoparticle Exposure in Healthy and
      Chronically Alcohol Fed Mice.
AB  - Silver (Ag) nanoparticles (NPs) are currently among one of the most widely used
      nanomaterials. This in turn, implies an increased risk of human and environmental
      exposure. Alcohol abuse is a global issue with millions of people in the general
      population affected by the associated adverse effects. The excessive consumption
      of alcohol is a prominent cause of chronic liver disease which manifest in
      multiple disorders. In this study, the adverse health effects of Ag NP exposure
      were investigated in models of alcoholic hepatic disease in vitro and in vivo.
      The data showed that Ag NP induced hepatic health effects were aggravated in the
      alcohol pretreated mice in comparison to controls with regards to an organ
      specific inflammatory response, changes in blood biochemistry, acute phase
      response and hepatic pathology. In addition, alcoholic disease influenced the
      organ's ability for recovery post-NP challenge. Additionally, it is demonstrated
      that the in vivo data correlated well with in vitro findings where ethanol
      pretreatment of hepatocytes resulted in significantly increased inflammatory
      response post-Ag NP exposure. To the best of our knowledge this is the first
      study of its kind to investigate nano-sized material-induced hepatic pathology in
      models representative of susceptible individuals (those with pre-existing alcohol
      liver disease) within the population. This is an area of research in the field of
      nanotoxicology, and in particular with regard to NP risk assessment that is
      almost entirely overlooked.

PMID- 28453774
TI  - Effect of dietary bacteriophage supplementation on internal organs, fecal
      excretion, and ileal immune response in laying hens challenged by Salmonella
      Enteritidis.
AB  - With the current researches on replacing antibiotics with different dietary
      interventions, bacteriophages (BP) are potential antimicrobial intervention
      because of their ability to affect specific bacteria. A study was conducted to
      evaluate the role of BP against Salmonella enterica serovar Enteritidis (SE) on
      SE internal organs colonization and ileum immune response in laying hens. Hens
      were challenged both orally and intracloacally with 108 cfu/mL cells of nalidixic
      acid resistant Salmonella Enteritidis (SENAR). Thirty-two Single Comb White
      Leghorns were randomly allocated to 4 dietary treatments: 1) unchallenged control
      (negative control; T1), 2) SENAR challenged control (positive control; T2), 3)
      SENAR challenged + 0.1% BP (T3), and 4) SENAR challenged + 0.2% BP (T4). The
      number of SENAR in the ceca was significantly reduced by 0.2% BP supplementation
      (P < 0.05) at 7 d post infection (dpi). The respective number of SENAR was
      reduced from 2.9 log cfu/gm in T2 and T3 to 2.0 log cfu/gm in T4. There was no
      significant effect of T3 on reduction of numbers of cecal SENAR. A significant
      reduction of SENAR was observed in the liver with gall bladder (LGB) from 0.75 in
      T2 to 0.18 log cfu/gm in T4. In the spleen, T4 significantly reduced (P < 0.05)
      SENAR to 0.56 log cfu/gm compared to T2 and T3 (0.94 log cfu/gm). There was no
      significant effect of T3 in reduction of prevalence of spleen SENAR. By
      supplementing 0.2% BP (T4), the SENAR in the ovary was reduced to 0 log cfu/gm.
      There was a significant reduction (P < 0.05) in fecal SENAR at 6 dpi by T4 (0.71
      log cfu/gm) compared to the positive control (1.57 log cfu/gm). The expression of
      interferon (IFN)-Gamma, interleukin (IL)-6, and IL-10 was significantly increased
      in the ileum by SENAR challenge compared to the negative control. This study
      suggests that apart from commonly used prebiotics or probiotics, BP are pathogen
      specific and can be used as one of the dietary strategies to reduce SE
      colonization and induce immune modulation in laying hens.

PMID- 28453773
TI  - Increased cerebrospinal fluid levels of GABA, testosterone and estradiol in women
      with polycystic ovary syndrome.
AB  - STUDY QUESTION: Do cerebrospinal fluid (CSF) concentrations of gamma-aminobutyric
      acid (GABA), testosterone (T) and estradiol (E2) differ in women with polycystic
      ovary syndrome (PCOS) as compared to eumenorrheic, ovulatory women (EW)? SUMMARY
      ANSWER: Women with PCOS displayed higher CSF levels of GABA and E2, and possibly
      T, than EW. WHAT IS KNOWN ALREADY: The chronic anovulation characteristic of PCOS
      has been attributed to increased central GnRH drive and resulting gonadotropin
      aberrations. Androgens are thought to regulate GABA, which in turn regulates the
      neural cascade that modulates GnRH drive. STUDY DESIGN, SIZE, DURATION: This
      cross-sectional observational study included 15 EW and 12 non-obese women with
      PCOS who consented to a lumbar puncture in addition to 24 h of serum blood
      collection at 15-min intervals. PARTICIPANTS/MATERIALS, SETTING, METHODS: In
      total, 27 women were studied at a the General Clinical Research Center (GCRC) at
      the University of Pittsburgh. Serum analytes included T, E2 and androstenedione.
      CSF analytes included GABA, glutamate, glucose, T and E2. MAIN RESULTS AND THE
      ROLE OF CHANCE: Women with PCOS had higher CSF GABA as compared to EW (9.04
      versus 7.04 MUmol/L, P < 0.05). CSF glucose and glutamate concentrations were
      similar between the two groups. CSF T was 52% higher (P = 0.1) and CSF E2 was 30%
      higher (P < 0.01) in women with PCOS compared to EW. Circulating T was 122%
      higher (P < 0.01) and circulating E2 was 75% higher (P < 0.01) in women with PCOS
      than in EW. LIMITATIONS REASONS FOR CAUTION: The study is limited by its small
      sample size and the technical limitations of measuring CSF analytes that are
      pulsatile and have short half-lives. WIDER IMPLICATIONS OF THE FINDINGS: Women
      with PCOS displayed significantly higher circulating levels of T and E2,
      significantly higher CSF levels of E2, and higher levels of CSF testosterone,
      although the latter was not statistically significant. A better understanding of
      the central milieu informs our understanding of the mechanisms mediating
      increased the GnRH drive in PCOS and lends a new perspective for understanding
      the presentation, pathogenesis and potential health consequences of PCOS,
      including gender identity issues. STUDY FUNDING/COMPETING INTEREST(S): No
      conflicts of interest. The study was funded by NIH grants to SLB (RO1-MH50748,
      U54-HD08610) and NIH RR-00056 to the General Clinical Research Center of the
      University of Pittsburgh. TRIAL REGISTRATION NUMBER: NCT01674426.

PMID- 28453775
TI  - Deconvoluting Kinase Inhibitor Induced Cardiotoxicity.
AB  - Many drugs designed to inhibit kinases have their clinical utility limited by
      cardiotoxicity-related label warnings or prescribing restrictions. While this
      liability is widely recognized, designing safer kinase inhibitors (KI) requires
      knowledge of the causative kinase(s). Efforts to unravel the kinases have
      encountered pharmacology with nearly prohibitive complexity. At therapeutically
      relevant concentrations, KIs show promiscuity distributed across the kinome.
      Here, to overcome this complexity, 65 KIs with known kinome-scale
      polypharmacology profiles were assessed for effects on cardiomyocyte (CM)
      beating. Changes in human iPSC-CM beat rate and amplitude were measured using
      label-free cellular impedance. Correlations between beat effects and kinase
      inhibition profiles were mined by computation analysis (Matthews Correlation
      Coefficient) to identify associated kinases. Thirty kinases met criteria of
      having (1) pharmacological inhibition correlated with CM beat changes, (2)
      expression in both human-induced pluripotent stem cell-derived cardiomyocytes and
      adult heart tissue, and (3) effects on CM beating following single gene
      knockdown. A subset of these 30 kinases were selected for mechanistic follow up.
      Examples of kinases regulating processes spanning the excitation-contraction
      cascade were identified, including calcium flux (RPS6KA3, IKBKE) and action
      potential duration (MAP4K2). Finally, a simple model was created to predict
      functional cardiotoxicity whereby inactivity at three sentinel kinases (RPS6KB1,
      FAK, STK35) showed exceptional accuracy in vitro and translated to clinical KI
      safety data. For drug discovery, identifying causative kinases and introducing a
      predictive model should transform the ability to design safer KI medicines. For
      cardiovascular biology, discovering kinases previously unrecognized as
      influencing cardiovascular biology should stimulate investigation of
      underappreciated signaling pathways.

PMID- 28453776
TI  - Modulating and evaluating receptor promiscuity through directed evolution and
      modeling.
AB  - The promiscuity of G-protein-coupled receptors (GPCRs) has broad implications in
      disease, pharmacology and biosensing. Promiscuity is a particularly crucial
      consideration for protein engineering, where the ability to modulate and model
      promiscuity is essential for developing desirable proteins. Here, we present
      methodologies for (i) modifying GPCR promiscuity using directed evolution and
      (ii) predicting receptor response and identifying important peptide features
      using quantitative structure-activity relationship models and grouping-exhaustive
      feature selection. We apply these methodologies to the yeast pheromone receptor
      Ste2 and its native ligand alpha-factor. Using directed evolution, we created
      Ste2 mutants with altered specificity toward a library of alpha-factor variants.
      We then used the  Vectors of Hydrophobic, Steric, and Electronic properties and
      partial least squares regression to characterize receptor-ligand interactions,
      identify important ligand positions and properties, and predict receptor response
      to novel ligands. Together, directed evolution and computational analysis enable
      the control and evaluation of GPCR promiscuity. These approaches should be
      broadly useful for the study and engineering of GPCRs and other protein-small
      molecule interactions.

PMID- 28453777
TI  - Mass spectrometry, immunoassay and valid steroid measurements in reproductive
      medicine and science.

PMID- 28453778
TI  - Exploring a causal role of DNA methylation in the relationship between maternal
      vitamin B12 during pregnancy and child's IQ at age 8, cognitive performance and
      educational attainment: a two-step Mendelian randomization study.
AB  - An adequate intake of vitamin B12 during pregnancy plays an important role in
      offspring neurodevelopment, potentially via epigenetic processes. We used a two
      step Mendelian randomization approach to assess whether DNA methylation plays a
      mediating and causal role in associations between maternal vitamin B12 status and
      offspring's cognition. Firstly, we estimated the causal effect of maternal
      vitamin B12 levels on cord blood DNA methylation using the maternal FUT2
      genotypes rs492602:A > G and rs1047781:A > T as proxies for circulating vitamin
      B12 levels in the Avon Longitudinal Study of Parents and Children (ALSPAC) and we
      tested the observed associations in a replication cohort. Secondly, we estimated
      the causal effect of DNA methylation on IQ using the offspring genotype at sites
      close to the methylated CpG site as a proxy for DNA methylation in ALSPAC and in
      a replication sample. The first step Mendelian randomization estimated that
      maternal vitamin B12 had a small causal effect on DNA methylation in offspring at
      three CpG sites, which was replicated for one of the sites. The second step
      Mendelian randomization found weak evidence of a causal effect of DNA methylation
      at two of these sites on childhood performance IQ which was replicated for one of
      the sites. The findings support a causal effect of maternal vitamin B12 levels on
      cord blood DNA methylation, and a causal effect of vitamin B12-responsive DNA
      methylation changes on children's cognition. Some limitations were identified and
      future studies using a similar approach should aim to overcome such issues.

PMID- 28453779
TI  - First Record of Lutzomyia (Lutzomyia) longipalpis (Diptera: Psychodidae:
      Phlebotominae) on the Trinational Frontier (Brazil-Peru-Bolivia) of South-Western
      Amazonia.
AB  - In South America, the main sand fly species involved in the transmission of
      Leishmania infantum chagasi (Cunha & Chagas, 1937), etiological agent of the
      visceral leishmaniasis (VL), is Lutzomyia longipalpis (Lutz & Neiva, 1912). The
      species has been recorded in Colombia, Venezuela, Bolivia, Argentina, Paraguay,
      Uruguay, and Brazil, where it is recorded in 24 of the 27 Brazilian states,
      except Acre, Amazonas, and Santa Catarina. Collections were carried out for one
      year (April 2013 to March 2014) using modified CDC light traps in different
      environments in Assis Brasil municipality, state of Acre. Two males of Lu.
      longipalpis were found in peridomiciliary location in a peri-urban area. This is
      the first record of the species in Acre. This finding may be considered by the
      health agencies located in the trinational frontier, and new collections are
      needed to evaluate the real distribution of the species.

PMID- 28453781
TI  - Dramatic science or scientific drama?

PMID- 28453782
TI  - SeMPI: a genome-based secondary metabolite prediction and identification web
      server.
AB  - The secondary metabolism of bacteria, fungi and plants yields a vast number of
      bioactive substances. The constantly increasing amount of published genomic data
      provides the opportunity for an efficient identification of gene clusters by
      genome mining. Conversely, for many natural products with resolved structures,
      the encoding gene clusters have not been identified yet. Even though genome
      mining tools have become significantly more efficient in the identification of
      biosynthetic gene clusters, structural elucidation of the actual secondary
      metabolite is still challenging, especially due to as yet unpredictable post
      modifications. Here, we introduce SeMPI, a web server providing a prediction and
      identification pipeline for natural products synthesized by polyketide synthases
      of type I modular. In order to limit the possible structures of PKS products and
      to include putative tailoring reactions, a structural comparison with annotated
      natural products was introduced. Furthermore, a benchmark was designed based on
      40 gene clusters with annotated PKS products. The web server of the pipeline
      (SeMPI) is freely available at: http://www.pharmaceutical
      bioinformatics.de/sempi.

PMID- 28453780
TI  - Variation in Maturity-Onset Diabetes of the Young Genes Influence Response to
      Interventions for Diabetes Prevention.
AB  - Context: Variation in genes that cause maturity-onset diabetes of the young
      (MODY) has been associated with diabetes incidence and glycemic traits.
      Objectives: This study aimed to determine whether genetic variation in MODY genes
      leads to differential responses to insulin-sensitizing interventions. Design and
      Setting: This was a secondary analysis of a multicenter, randomized clinical
      trial, the Diabetes Prevention Program (DPP), involving 27 US academic
      institutions. We genotyped 22 missense and 221 common variants in the MODY
      causing genes in the participants in the DPP. Participants and Interventions: The
      study included 2806 genotyped DPP participants randomized to receive intensive
      lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944). Main
      Outcome Measures: Association of MODY genetic variants with diabetes incidence at
      a median of 3 years and measures of 1-year beta-cell function, insulinogenic
      index, and oral disposition index. Analyses were stratified by treatment group
      for significant single-nucleotide polymorphism * treatment interaction (Pint <
      0.05). Sequence kernel association tests examined the association between an
      aggregate of rare missense variants and insulinogenic traits. Results: After 1
      year, the minor allele of rs3212185 (HNF4A) was associated with improved beta
      cell function in the metformin and lifestyle groups but not the placebo group;
      the minor allele of rs6719578 (NEUROD1) was associated with an increase in
      insulin secretion in the metformin group but not in the placebo and lifestyle
      groups. Conclusions: These results provide evidence that genetic variation among
      MODY genes may influence response to insulin-sensitizing interventions.

PMID- 28453783
TI  - Sleep-Related Breathing Disorders in Chiari Malformation Type 1: A Prospective
      Study of 90 Patients.
AB  - Study objective: The aim of the present study is to describe the prevalence of
      sleep disorders in a large group of patients with Chiari malformation type 1 (CM
      1) and determine the presence of risk factors associated with these
      abnormalities. Methods: Prospective study with consecutive patient selection. We
      included 90 adult patients with CM-1, defined by the presence of a cerebellar
      tonsillar descent (TD) >=3 mm. Clinical, neuroradiological studies, and nocturnal
      polysomnography (PSG) was carried out. In addition, patients were also
      subclassified into 2 CM subtypes: CM-1, with the obex above the foramen magnum
      (FM) and CM-1.5, in which along with a TD >=3 mm, the obex was located below the
      FM. Results: We observed a high prevalence (50%) of sleep-related breathing
      disorders (SRBDs) with predominant hypopnea. Only six patients showed a central
      apnea index of >=5. Hypoventilation was observed in only three patients. SRBD
      severity was associated with male sex, older age, excess weight, and the presence
      of hydrocephalus. No differences in clinical or PSG parameters were found when
      comparing CM subtypes (CM-1 and CM-1.5). Sleep architecture study showed
      decreased sleep efficiency with an increase in arousal and waking after sleep
      onset. The presence of SRBDs was found to be associated with poorer sleep
      architecture parameters. Conclusions: This study confirms a high prevalence of
      SRBDs in patients with CM-1 and CM-1.5, with a predominant obstructive component.
      Nocturnal PSG recordings should be systematically conducted in these patients,
      especially those who are male, older, or overweight or those who present
      hydrocephalus.

PMID- 28453784
TI  - Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived
      extracellular vesicles of glioblastoma patients.
AB  - Background: RNAs within extracellular vesicles (EVs) have potential as diagnostic
      biomarkers for patients with cancer and are identified in a variety of biofluids.
      Glioblastomas (GBMs) release EVs containing RNA into cerebrospinal fluid (CSF).
      Here we describe a multi-institutional study of RNA extracted from CSF-derived
      EVs of GBM patients to detect the presence of tumor-associated amplifications and
      mutations in epidermal growth factor receptor (EGFR). Methods: CSF and matching
      tumor tissue were obtained from patients undergoing resection of GBMs. We
      determined wild-type (wt)EGFR DNA copy number amplification, as well as wtEGFR
      and EGFR variant (v)III RNA expression in tumor samples. We also characterized
      wtEGFR and EGFRvIII RNA expression in CSF-derived EVs. Results: EGFRvIII-positive
      tumors had significantly greater wtEGFR DNA amplification (P = 0.02) and RNA
      expression (P = 0.03), and EGFRvIII-positive CSF-derived EVs had significantly
      more wtEGFR RNA expression (P = 0.004). EGFRvIII was detected in CSF-derived EVs
      for 14 of the 23 EGFRvIII tissue-positive GBM patients. Conversely, only one of
      the 48 EGFRvIII tissue-negative patients had the EGFRvIII mutation detected in
      their CSF-derived EVs. These results yield a sensitivity of 61% and a specificity
      of 98% for the utility of CSF-derived EVs to detect an EGFRvIII-positive GBM.
      Conclusion: Our results demonstrate CSF-derived EVs contain RNA signatures
      reflective of the underlying molecular genetic status of GBMs in terms of wtEGFR
      expression and EGFRvIII status. The high specificity of the CSF-derived EV
      diagnostic test gives us an accurate determination of positive EGFRvIII tumor
      status and is essentially a less invasive "liquid biopsy" that might direct
      mutation-specific therapies for GBMs.

PMID- 28453787
TI  - Reply I. Cord blood androgen measurement: the importance of assay validation.

PMID- 28453785
TI  - Structural and functional characterization of the PNKP-XRCC4-LigIV DNA repair
      complex.
AB  - Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling
      eukaryotic cells. NHEJ relies on polynucleotide kinase/phosphatase (PNKP), which
      generates 5?-phosphate/3?-hydroxyl DNA termini that are critical for ligation by
      the NHEJ DNA ligase, LigIV. PNKP and LigIV require the NHEJ scaffolding protein,
      XRCC4. The PNKP FHA domain binds to the CK2-phosphorylated XRCC4 C-terminal tail,
      while LigIV uses its tandem BRCT repeats to bind the XRCC4 coiled-coil. Yet, the
      assembled PNKP-XRCC4-LigIV complex remains uncharacterized. Here, we report
      purification and characterization of a recombinant PNKP-XRCC4-LigIV complex. We
      show that the stable binding of PNKP in this complex requires XRCC4
      phosphorylation and that only one PNKP protomer binds per XRCC4 dimer. Small
      angle X-ray scattering (SAXS) reveals a flexible multi-state complex that
      suggests that both the PNKP FHA and catalytic domains contact the XRCC4 coiled
      coil and LigIV BRCT repeats. Hydrogen-deuterium exchange indicates protection of
      a surface on the PNKP phosphatase domain that may contact XRCC4-LigIV. A mutation
      on this surface (E326K) causes the hereditary neuro-developmental disorder, MCSZ.
      This mutation impairs PNKP recruitment to damaged DNA in human cells and provides
      a possible disease mechanism. Together, this work unveils multipoint contacts
      between PNKP and XRCC4-LigIV that regulate PNKP recruitment and activity within
      NHEJ.

PMID- 28453786
TI  - A-to-I RNA Editing in the Earliest-Diverging Eumetazoan Phyla.
AB  - The highly conserved ADAR enzymes, found in all multicellular metazoans, catalyze
      the editing of mRNA transcripts by the deamination of adenosines to inosines.
      This type of editing has two general outcomes: site specific editing, which
      frequently leads to recoding, and clustered editing, which is usually found in
      transcribed genomic repeats. Here, for the first time, we looked for both editing
      of isolated sites and clustered, non-specific sites in a basal metazoan, the
      coral Acropora millepora during spawning event, in order to reveal its editing
      pattern. We found that the coral editome resembles the mammalian one: it contains
      more than 500,000 sites, virtually all of which are clustered in non-coding
      regions that are enriched for predicted dsRNA structures. RNA editing levels were
      increased during spawning and increased further still in newly released gametes.
      This may suggest that editing plays a role in introducing variability in coral
      gametes.

PMID- 28453788
TI  - From the Cover: Usage of Dexamethasone Increases the Risk of Cranial Neural Crest
      Dysplasia in the Chick Embryo.
AB  - Dexamethasone (Dex) is commonly used in the treatment of a variety of benign and
      malignant conditions. Unfortunately, although it has a variety of teratogenic
      effects, it remains used in clinical practice for pregnant women mainly due to
      limited alternatives. However, there is limited knowledge of the mechanisms that
      lead to the observed teratogenic effects. In this study, the effects of Dex
      during embryogenesis on neural crest development were evaluated in the early
      chick embryos. First, we demonstrated that 100 ul 10-6 M Dex treatment leads to
      craniofacial developmental defects, and also retards embryo growth and plausibly
      can cause embryo demise. Second, we demonstrated that Dex represses the
      production of HNK-1, PAX7, and AP-2alpha labeled cranial neural crest cells, the
      progenitor cells of the craniofacial skeleton. Third, double immunofluorescent
      staining of pHIS3/PAX7 and AP-2alpha/c-Caspase3 revealed that Dex promotes cell
      apoptosis but does not change cell proliferation rates. Last, fibroblast growth
      factor signaling molecules were inhibited by Dex treatment. Dex also inhibited
      neural crest cells production by repressing Msx1 expression in the developing
      neural tube and by altering expression of epithelial-mesenchymal transition
      related adhesion molecules and cell migration genes. Overall, we obtained
      experimental evidence that Dex treatment during embryogenesis disrupts cranial
      neural crest development which in turn causes defective cranial bone development.

PMID- 28453790
TI  - Does the Law on Compensation for Research-Related Injury in the UK, Australia,
      and New Zealand Meet Ethical Requirements?
AB  - Despite a consensus that society owes an ethical obligation to compensate for
      research-related injury, and that no-fault is the best ethical response, an
      assessment of the compensation arrangements in place in the UK, Australia and New
      Zealand shows that in general compensation arrangements fall below this ethical
      expectation. Most subjects rely on ex gratia payment or an unenforceable
      assurance of payment in the event of injury. It is also likely that, given
      significant deficiencies in participant information about compensation
      arrangements in place for trials recommended by the supervisory ethics agencies
      in each jurisdiction, subjects only find out about their financial exposure in
      the event of injury. Industry-drafted guidelines governing compensation in
      commercially sponsored trials do not protect subjects' interests, but operate
      primarily to protect the interests of industry. The article considers potential
      solutions to the ethical deficiency of the compensation arrangements, and argues
      that the ethical corollary of the fact that society is the ultimate beneficiary
      of its members' participation in clinical research, is that society as a whole
      should bear the cost of participant injuries, through establishment of a central
      no-fault compensation fund financed either by the state or those directly
      involved in biomedical research.

PMID- 28453789
TI  - Association Between Serum Tumor Necrosis Factor Receptor 1 and Trajectories of
      Functional Status: The Northern Manhattan Study.
AB  - We hypothesized that tumor necrosis factor receptor 1 (TNFR1) levels are
      associated with long-term trajectories of functional status independently of
      vascular risk factors and the occurrence of stroke and myocardial infarction (MI)
      during follow-up. In the Northern Manhattan Study, stroke-free persons aged >=40
      years in northern Manhattan (New York, New York) had annual assessments with the
      Barthel index (BI) for a median of 13 years (1993-2015). Assessment of baseline
      demographic factors, risk factors, and laboratory studies included measurement of
      TNFR1 (n = 1,863). Generalized estimating equations models were used to estimate
      standardized associations between TNFR1 and 1) baseline functional status and 2)
      change in function over time, adjusting for demographic factors, vascular risk
      factors, social variables, cognition, and depression, as well as stroke and MI
      occurrence during follow-up. The mean age of participants was 70 (standard
      deviation (SD), 10) years; 66% were women, and 55% were Hispanic. The mean TNFR1
      level was 2.57 mg/L. TNFR1 was associated with baseline BI (-0.93 BI points per
      SD increment in TNFR1; 95% confidence interval: -1.59, -0.26) and change over
      time (-0.36 BI points per year per SD increment in TNFR1; 95% confidence
      interval: -0.69, -0.03). In this large population-based study, higher TNFR1
      levels were associated with greater baseline disability and disability over time,
      even with adjustment for baseline covariates and stroke and MI occurrence during
      follow-up.

PMID- 28453791
TI  - Progranulin functions as a cathepsin D chaperone to stimulate axonal outgrowth in
      vivo.
AB  - Loss of function mutations in progranulin (GRN) cause frontotemporal dementia,
      but how GRN haploinsufficiency causes neuronal dysfunction remains unclear. We
      previously showed that GRN is neurotrophic in vitro. Here, we used an in vivo
      axonal outgrowth system and observed a delayed recovery in GRN-/- mice after
      facial nerve injury. This deficit was rescued by reintroduction of human GRN and
      relied on its C-terminus and on neuronal GRN production. Transcriptome analysis
      of the facial motor nucleus post injury identified cathepsin D (CTSD) as the most
      upregulated gene. In aged GRN-/- cortices, CTSD was also upregulated, but the
      relative CTSD activity was reduced and improved upon exogenous GRN addition.
      Moreover, GRN and its C-terminal granulin domain granulinE (GrnE) both stimulated
      the proteolytic activity of CTSD in vitro. Pull-down experiments confirmed a
      direct interaction between GRN and CTSD. This interaction was also observed with
      GrnE and stabilized the CTSD enzyme at different temperatures. Investigating the
      importance of this interaction for axonal regeneration in vivo we found that,
      although individually tolerated, a combined reduction of GRN and CTSD
      synergistically reduced axonal outgrowth. Our data links the neurotrophic effect
      of GRN and GrnE with a lysosomal chaperone function on CTSD to maintain its
      proteolytic capacity.

PMID- 28453792
TI  - Triple valve surgery through a less invasive approach: early and mid-term
      results.
AB  - OBJECTIVES: A partial upper sternotomy has become established as a less invasive
      approach mainly for single and double valve surgery. This report evaluates the
      clinical outcomes of triple valve surgery performed through a partial upper
      sternotomy. METHODS: We reviewed the medical records of 37 consecutive patients
      (28 men, 76%) who underwent triple valve surgery through a partial upper
      sternotomy between 2005 and 2015. The patients' mean age was 67 +/- 17 years; 27
      (73%) were in New York Heart Association Class III or IV. Aortic and mitral valve
      insufficiency was more common than stenosis. Ninety-three percent of surviving
      patients were followed for a mean period of 58 +/- 24 months. RESULTS: Aortic
      valve procedures consisted of 24 (65%) replacements and 13 (35%) repairs. The
      mitral valve was repaired in 28 (76%) patients, whereas tricuspid valve repair
      was feasible in all patients. No conversion to full sternotomy was necessary.
      Myocardial infarction was not observed. Chest tube drainage was 330 +/- 190 ml,
      and 4 patients required reopening for bleeding (1, 3%) or tamponade (3, 8%). One
      stroke was observed due to heparin-induced thrombocytopaenia after initial
      unremarkable neurological recovery. Early mortality included 5 (13.5%) patients.
      Actuarial survival at 5 years was 52 +/- 10%. CONCLUSIONS: A partial upper
      sternotomy provides adequate exposure to all heart valves. We did not experience
      technical limitations with this approach. Wound dehiscence, postoperative
      bleeding, intensive care unit and hospital stay and early deaths were low
      compared to data from other published series of triple valve surgery through a
      full median sternotomy. Early and mid-term outcomes were not adversely affected
      by this less invasive approach.

PMID- 28453793
TI  - Impact of gender on long-term outcomes after surgical repair for acute Stanford A
      aortic dissection: a propensity score matched analysis.
AB  - OBJECTIVES: Previous research suggests that female gender is associated with
      increased mortality rates after surgery for Stanford A acute aortic dissection
      (AAD). However, women with AAD usually present with different clinical symptoms
      that may bias outcomes. Moreover, there is a lack of long-term results regarding
      overall mortality and freedom from major cerebrovascular events. We analysed the
      impact of gender on long-term outcomes after surgery for Stanford A AAD by
      comparing genders with similar risk profiles using propensity score matching.
      METHODS: A total of 240 patients operated for Stanford A AAD were included in
      this study. To control for selection bias and other confounders, propensity score
      matching was applied to gender groups. RESULTS: After propensity score matching,
      the gender groups were well balanced in terms of risk profiles. There were no
      statistically significant differences regarding duration of cardiopulmonary
      bypass ( P  = 0.165) and duration of aortic cross-clamp time ( P  = 0.111).
      Female patients received less fresh frozen plasma ( P  = 0.021), had shorter
      stays in the intensive care unit ( P  = 0.031), lower incidence of temporary
      neurological dysfunction ( P  < 0.001) and lower incidence of dialysis ( P  =
      0.008). There were no significant differences regarding intraoperative mortality
      ( P  = 1.000), 30-day mortality ( P  = 0.271), long-term overall cumulative
      survival ( P  = 0.954) and long-term freedom from cerebrovascular events ( P  =
      0.235) with up to a 9-year follow-up. CONCLUSIONS: Considering patients with
      similar risk profiles, female gender per se is not associated with worse long
      term survival and freedom from stroke after surgical aortic repair. Moreover,
      female patients might even benefit from a smoother early postoperative course and
      lower incidence of early postoperative complications.

PMID- 28453794
TI  - Blood flow competition after aortic valve bypass: an evaluation using
      computational fluid dynamics.
AB  - OBJECTIVES: Aortic valve bypass (AVB) (apico-aortic conduit) remains an effective
      surgical alternative for patients in whom surgical aortic valve replacement or
      transcatheter aortic valve implantation is not feasible. However, specific
      complications include thrombus formation, possibly caused by stagnation arising
      from flow competition between the antegrade and retrograde flow, but this has not
      been fully investigated. The aim of this study was to analyse flow
      characteristics after AVB and to elucidate mechanisms of intra-aortic thrombus
      using computational fluid dynamics (CFD). METHODS: Flow simulation was performed
      on data obtained from a 73-year-old postoperative AVB patient. Three-dimensional
      cine phase-contrast magnetic resonance imaging at 3 Tesla was used to acquire
      flow data and to set up the simulation. The vascular geometry was reconstructed
      using computed tomography angiograms. Flow simulations were implemented at
      various ratios of the flow rate between the ascending aorta and the graft.
      Results were visualized by streamline and particle tracing. RESULTS: CFD
      demonstrated stagnation in the ascending aorta-arch when retrograde flow was
      dominant, indicating that the risk of thrombus formation exists in the ascending
      arch in cases with severe aortic stenosis and/or poor left ventricular function.
      Meanwhile, stagnation was observed in the proximal descending aorta when the
      antegrade and retrograde flow were equivalent, suggesting that the descending
      aorta is critical when aortic stenosis is not severe. CONCLUSIONS: Flow
      stagnation in the aorta which may cause thrombus was observed when retrograde
      flow was dominant and antegrade/retrograde flows were equivalent. Our results
      suggest that anticoagulants might be recommended even in patients who receive
      biological valves.

PMID- 28453795
TI  - Closing the gap in paediatric ventricular assist device therapy with the Berlin
      Heart EXCOR(r) 15-ml pump.
AB  - OBJECTIVES: The Berlin Heart EXCOR (r) (EXCOR) paediatric ventricular assist
      device is used worldwide for mechanical support of infants and small children
      with end-stage heart failure. A clinically important gap between the smallest
      EXCOR blood pump (10 ml) and the next larger size (25 ml) limited the choice of
      pump size in patients with a body surface area (BSA) between 0.33 and 0.5 m 2 .
      We present the first clinical experience from the early product surveillance
      (EPS) of the new EXCOR 15-ml blood pump. METHODS: After CE and U.S. Food and Drug
      Administration approval in January 2013, 20 patients with a mean age of 1.6 years
      (range 0.5-3.5 years) and a mean BSA of 0.45 m 2 (range 0.33-0.59 m 2 ) were
      enrolled in the EPS. The main diagnosis was idiopathic cardiomyopathy in 13
      patients; the majority ( n =  16) of children were in INTERMACS level 1 or 2.
      Data from high-volume paediatric transplant centres were collected prospectively
      for a defined follow-up period of 60 days after device implantation. RESULTS:
      Mean time on the EXCOR 15-ml blood pump was 43 days; the survival rate was 100%
      at the end of the EPS period. Seven patients underwent a heart transplant from
      the device; 2 children were weaned; and 11 patients remained on support.
      Infection of cannula exit sites occurred in 3 patients. Two patients had minor
      thromboembolic strokes but made a complete neurological recovery. CONCLUSIONS:
      The new EXCOR 15-ml blood pump demonstrated optimal ventricular assist device
      support of children with a BSA of 0.33-0.5 m 2 .

PMID- 28453796
TI  - Descendo-bifemoral bypass grafting and renal artery revascularization to treat
      complex obliterative arteriopathy.
AB  - OBJECTIVES: Our goal was to describe a new standardized approach in patients with
      extensive obliterative arteriopathy aimed at distal revascularization and
      surgical kidney recruitment via descendo-bifemoral bypass grafting and renal
      artery revascularization. METHODS: Three patients with Leriche's syndrome and
      either a compromised single kidney or unilateral significant renal artery
      stenosis were treated with a standardized surgical approach, restoration of
      distal perfusion via descendo-bifemoral bypass with synchronous ( n  = 2) left
      sided renal artery revascularization or metachronous ( n  = 1) right-sided renal
      artery revascularization. RESULTS: The intended surgical aim was achieved
      successfully in all 3 cases. All patients showed a decline in serum creatinine
      levels. One patient who needed substitution therapy was free from dialysis 3
      months after surgery. Additionally, blood pressure management was substantially
      reduced because uncontrolled peak systolic episodes were no longer observed and
      pharmacotherapeutic agents could be partially withdrawn. CONCLUSIONS: Distal
      revascularization and surgical kidney recruitment via descendo-bifemoral bypass
      and renal artery revascularization is a promising option to treat complex
      obliterative arteriopathy.

PMID- 28453797
TI  - Coronary artery bypass surgery in young adults: excellent perioperative results
      and long-term survival.
AB  - OBJECTIVES: To analyse perioperative results, long-term survival and freedom from
      complications after coronary artery bypass grafting (CABG) in young adults.
      METHODS: A total of 163 patients, 40 years old or younger, had isolated CABG from
      January 1989 to December 2010. Pre- and perioperative demographic and clinical
      data were retrieved from a prospectively organised database. Follow-up data were
      obtained by letter or telephone interviews. The mean age of the patients was 37.6
      +/- 2.9 years and 146 were men (90%). Fifty-three patients (32.5%) had angina
      class III/IV; 106 (65.0%), previous myocardial infarction; and 23 (14.1%),
      impaired left ventricular function (ejection fraction <40%). Indication for
      surgery was 3-vessel disease in 101 cases (62.0%), 2-vessel disease in 30 (18.4%)
      and single-vessel disease in 32 (19.6%). The left main stem was affected in 16
      patients (9.8%). The mean EuroSCORE II was 0.92 +/- 0.71. A total of 417 grafts
      were constructed (mean 2.6 grafts/patient), 247 of which (59.2%) were arterial.
      RESULTS: There were no in-hospital deaths. The mean hospital stay was 7.1 +/- 4.0
      days. Four patients (2.5%) were lost to follow-up, which extended from 3 to 25
      years (mean 15.1 +/- 5.5 years). There were 22 late deaths, 72.7% of cardiac or
      unknown origin. The 5-, 10- and 20-year survival rates were 98.7 +/- 10.9, 95.2
      +/- 1.8 and 79.4 +/- 4.4%, respectively. Twenty-six patients (18.1%) had non
      fatal cardiac adverse complications (myocardial infarct, percutaneous re
      revascularization or class III/IV angina), for 5-, 10- and 20-year freedom from
      complications of 97.9 +/- 1.2, 91.9 +/- 2.5 and 65.7 +/- 7.1%, respectively.
      Twenty-two patients (17.5%) needed re-revascularization, for 5-, 10- and 20-year
      freedom from re-revascularization of 97.6 +/- 1.4, 91.9 +/- 2.6 and 69.5 +/-
      6.7%, respectively. CONCLUSIONS: Despite the aggressive nature of coronary artery
      disease in young patients, perioperative death and morbidity rates are low, with
      good long-term survival and low rates of re-revascularization.

PMID- 28453798
TI  - Caveolin 2: a facultative marker of unfavourable prognosis in long-term patency
      rate of internal thoracic artery grafts used in coronary artery bypass grafting.
      Preliminary report.
AB  - OBJECTIVES: Intimal hyperplasia leading to graft failure in patients undergoing
      coronary artery bypass grafting (CABG) is related to vascular smooth muscle cells
      (SMCs) proliferation. SMCs respond to a variety of mediators, the most important
      of which is platelet-derived growth factor (PDGF). The platelet-derived growth
      factor-induced cellular response has been shown to be mediated by caveolins. The
      aim of this study was to analyze CAV1-3 expression in internal thoracic artery
      (ITA) grafts used in CABG and correlate their expression with graft occlusion.
      METHODS: Six hundred patients undergoing CABG with the use of ITA grafts between
      2008 and 2014 were enrolled into this prospective study. CAV1-3 expression in the
      ITA grafts was analyzed prior to graft transplantation into the coronary
      circulation via immunohistochemistry. Estimated caveolins expression pattern was
      then correlated with the occurrence of ITA graft failure observed within 24
      months of surgery. RESULTS: Thirty-four patients developed ITA graft failure
      (subgroup A) and 566 study participants presented no adverse events (subgroup B).
      CAV1 and CAV3 expression levels in SMCs of the tunica media of the ITA grafts did
      not differ between the study subgroups and were not associated with the risk of
      graft failure. CAV2 was expressed within SMCs of the ITA grafts in 94.1% of the
      patients from subgroup A and 2.5% from subgroup B, and its expression was
      associated with ITA graft occlusion observed within 24-months after CABG.
      CONCLUSIONS: CAV2 expression in SMCs of the tunica media in autologous ITA
      transplants might indicate the risk of graft failure.

PMID- 28453799
TI  - Early to mid-term results after total cavopulmonary connection performed in the
      second decade of life.
AB  - OBJECTIVES: Total cavopulmonary connection (TCPC) performed in the second decade
      of life has rarely been studied. Thus, we investigated (bicentric study) early
      and late morbidity and mortality following completion of TCPC in these patients.
      METHODS: From January 1999 to June 2014, 63 patients (14.5 +/- 2.9 years)
      underwent TCPC (extracardiac conduit). Palliation before completion was an
      isolated bidirectional cavopulmonary shunt (BCPS) in 3 patients or BCPS
      associated with additional pulmonary blood flow (APBF) that was either antegrade
      (Group 1) in 38 (63%) or retrograde (Group 2) in 22 (37%). Preoperative and
      perioperative data were reviewed retrospectively. RESULTS: Mean pulmonary
      arterial and ventricular end-diastolic pressures were 12.2 and 9.2 mmHg,
      respectively. Mean Nakata index was 279 +/- 123 and 228 +/- 87 mm 2 /m 2 in
      Groups 1 and 2, respectively ( P  =   0.01). Aortic cross-clamping was performed
      in 22 from Group 1 and 8 from Group 2 ( P  =   0.04). Mean follow-up was 4.57
      years [0.8-15]. Nine patients had prolonged stays in the intensive care unit (>6
      days). There were 1 early and 2 late deaths (non-cardiac related). Actuarial
      survival was 96% at 4 years. At last follow-up, single-ventricle function
      remained normal or improved in all patients (Group 1) compared to 82% in Group 2
      ( P  =   0.02). New York Heart Association (NYHA) class had improved in both
      groups: 47 patients were NYHA class II and 16 class III preoperatively vs 50
      class I and 10 class II postoperatively ( P  <   0.001). CONCLUSIONS: Single
      ventricle palliation with BCPS and APBF allowed completion of TCPC in the second
      decade of life, with encouraging mid-term results. However, BCPS with retrograde
      APBF was associated with single-ventricle dysfunction: thus, this technique needs
      to be used cautiously as long-lasting palliation.

PMID- 28453800
TI  - Coronary sinus injury resulting from endarterectomy during multivessel bypass
      surgery.
AB  - Coronary sinus injury is a very rare complication of cardiac surgery and is
      usually related to coronary sinus perfusion catheter placement for retrograde
      cardioplegia infusion. It can be either a catheter-related perforation or high
      perfusion pressure-related injury to the coronary sinus. Primary repair of the
      coronary sinus or over-sewing are two possible options to resolve this
      complication. Decellularized extracellular matrix from porcine intestinal
      submucosa is widely used as an approved material for repairing cardiac
      structures. We report a case of coronary sinus stenosis resulting from coronary
      artery endarterectomy during multivessel coronary artery bypass surgery, causing
      injury to the proximal part of the middle cardiac vein (MCV). Closure of the MCV
      resulted in a coronary sinus obstruction that was bypassed with a CorMatrix tube
      graft from the coronary sinus of the MVC to the right atrium.

PMID- 28453801
TI  - Does perioperative chemotherapy improve survival in patients with resectable lung
      metastases of colorectal cancer?
AB  - A best evidence topic was constructed according to a structured protocol. The
      question addressed was whether the administration of perioperative chemotherapy
      (CT) is effective in improving survival in patients with resectable lung
      metastases of colorectal cancer (CRC). Of the 44 papers found using a report
      search, 6 investigated the effect of perioperative CT (adjuvant-CT, preoperative
      CT or both) on outcomes in patients undergoing lung metastasectomy for CRC. These
      6 studies presented the best evidence to answer the clinical question. The
      authors, journal, date and country of publication, study type, group studied,
      relevant outcomes and results of these papers are given. Overall, none of the
      studies were successful in demonstrating that CT had an independent effect on
      overall survival in patients undergoing lung resection surgery for CRC
      metastasis. Indeed, beneficial outcomes have been shown in particular sub-groups
      of patients: multiple metastases, metachronous lung metastasis, low-risk
      patients, particular molecular marker expression and oxaliplatin-based regimen.
      All the studies indicated a benefit in disease-free survival or progression-free
      survival. Administration of tailored perioperative CT might be effective after an
      accurate patient selection. We conclude that the current evidence does not
      support the administration of unselective perioperative CT in patients with
      resectable lung metastases of colorectal cancer.

PMID- 28453802
TI  - Propensity matched comparison of extrapleural pneumonectomy and
      pleurectomy/decortication for mesothelioma patients.
AB  - OBJECTIVES: The objective of this retrospective study was to assess perioperative
      outcomes, overall survival and freedom from recurrence after induction
      chemotherapy followed by extrapleural pneumonectomy (EPP) or
      pleurectomy/decortication (P/D) in patients with mesothelioma in a propensity
      score matched analysis. METHODS: Between September 1999 and August 2015, 167
      patients received multimodality treatment (platinum-based chemotherapy followed
      by EPP [ n =  141] or P/D [ n =  26]). We performed 2:1 propensity score matching
      for gender, laterality, epithelioid histological subtype and International
      Mesothelioma Interest Group (iMig) stage (52 EPP and 26 P/D). RESULTS:
      Postoperative major morbidity (48% vs 58%, P =  0.5) was similar in both groups;
      however, the complication profile and severity were different and favoured P/D;
      the 90-day mortality (8% vs 0%, P =  0.3) rate was lower in P/D although not
      statistically significant. Prolonged air leak (>=10 days) occurred in 15 patients
      (58%) undergoing P/D. The intensive care unit stay was significantly longer after
      EPP ( P =  0.001). Freedom from recurrence was similar for both groups (EPP:
      median 15 months, 95% confidence interval [CI]: 10-21; P/D: 13 months, 95% CI: 11
      17) ( P =  0.2). Overall survival was significantly longer for patients
      undergoing P/D (median 32 months, 95% CI: 29-35) compared to EPP (23 months, 95%
      CI: 21-25) ( P =  0.031), but in the P/D group many cases were censored (73%) and
      the follow-up time was relatively short. CONCLUSIONS: P/D and EPP seem to have
      similar rates of major morbidity, although the profile of complications is
      different and more severe after EPP. Freedom from recurrence is comparable in
      both groups whereas improved overall survival needs to be confirmed in a large
      patient group with longer follow-up.

PMID- 28453803
TI  - Does cervical lymph node recurrence after oesophagectomy or definitive
      chemoradiotherapy for thoracic oesophageal squamous cell carcinoma benefit from
      salvage treatment?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was 'Does cervical lymph node recurrence after
      oesophagectomy or definitive chemoradiotherapy for thoracic oesophageal squamous
      cell carcinoma benefit from salvage treatment?' Altogether, 659 articles were
      found using the reported search, of which 8 represented the best evidence to
      answer the clinical question. The authors, journal, date, country of publication,
      patient group studied, study type, relevant outcomes and results of these
      articles were tabulated. All were retrospective or institutional reports. Seven
      of the 8 articles suggested that cervical lymphadenectomy (LD) or multimodal
      treatment with LD and radiotherapy (RT)/chemoradiotherapy (CRT) was associated
      with good outcomes in patients with cervical lymph node (LN) recurrence after
      curative oesophagectomy for thoracic oesophageal squamous cell carcinoma (ESCC).
      Salvage cervical LD was the main treatment and could achieve locoregional disease
      control and prolonged survival. It was safe with no postoperative mortality,
      although minor LD complications such as recurrent laryngeal nerve palsy were
      observed. Most reports highlighted that a solitary cervical LN relapse after
      curative oesophagectomy could be considered a good prognostic indicator for
      salvage cervical LD or multimodal treatment. Patients with microscopic residual
      tumour after salvage cervical LD or suspected extensive metastasis might benefit
      from a combination of LD and CRT. One article described salvage RT alone, again
      with a positive effect on survival. Conversely, data suggested that salvage LD in
      patients after definitive CRT for thoracic ESCC was not likely to control
      locoregional disease.

PMID- 28453804
TI  - Left video-assisted thoracoscopic surgery for hemidiaphragm traumatic rupture
      repair.
AB  - Diaphragmatic laceration is not a rare condition after blunt thoraco-abdominal
      trauma following road traffic accidents. Diagnosis is sometime difficult and
      clinical presentation devious. Video-assisted thoracic surgery is a safe approach
      in order to confirm diagnosis and treat, like in this this case of an 86-year-old
      lady with grade IV injury.

PMID- 28453805
TI  - Pathological investigation of graft-related oesophageal fistula.
AB  - Oesophageal fistulae after thoracic endovascular aneurysm repair (TEVAR) for
      thoracic aortic aneurysm (TAA) have been reported, although the causes are
      unknown. One hypothesis is that the structural configuration of the aortic
      aneurysm, as it protrudes towards the oesophagus, may affect oesophageal fistula
      formation. The pathological findings of an oesophageal fistula following TEVAR
      are reviewed here. This report presents the case of a 68-year-old man with a
      stent graft-related oesophageal fistula after TEVAR for TAA. The oesophageal
      fistula suddenly appeared on the 11th day after TEVAR, and oesophagectomy was
      performed, without stent graft extirpation. The pathological findings showed
      neutrophil infiltration from the adventitia to the mucosa and congestion in the
      capillaries of the oesophageal wall around the site of penetration and no
      bacterial infection. There have been reports with logical hypotheses about the
      causes of stent graft-related oesophageal fistulae. Our pathological findings
      support the theory that pressure necrosis or ischaemic insult by physical
      compression of a rigid thrombosed aneurysm may result in fistula formation. For
      descending aortic aneurysms that protrude toward the oesophagus, caution must be
      exercised to prevent oesophageal fistula formation after TEVAR.

PMID- 28453806
TI  - Coil embolization for pulmonary artery injury caused by chest tube drainage.
AB  - Pulmonary artery injury caused by chest tube drainage is rare, but it requires
      prompt diagnosis to perform urgent surgical repair. We report that a 53-year-old
      man who suffered from pulmonary artery injury by chest tube drainage was
      successfully treated by coil embolization.

PMID- 28453807
TI  - Attrition in patients with single ventricle and trisomy 21: outcomes after a
      total cavopulmonary connection.
AB  - OBJECTIVES: Data are limited regarding the management of children with trisomy 21
      (T21) syndrome and a functional single ventricle (FSV). We evaluated patients
      with T21 and a FSV who had a total cavopulmonary connection (TCPC). METHODS: From
      September 1999 to August 2012, 139 patients with a FSV underwent a TCPC. Sixty
      five had unbalanced atrioventricular septal defect. Thirteen had T21. Three (of
      13) had heterotaxy syndrome. The mean age at the Fontan operation was 27.6 +/-
      12.1 months. RESULTS: The initial procedure was pulmonary artery banding in 9
      patients, systemic-to-pulmonary shunt in 2 and Damus-Kaye-Stansel/Norwood
      procedure in 2. Median follow-up was 69 months (interquartile range 25-75, 21
      99). There was 1 death after a Damus-Kaye-Stansel/Norwood procedure and one
      interstage death after a bidirectional Glenn procedure. Nine (of 11) survivors
      underwent a Fontan operation. A fenestrated Fontan procedure was the predominate
      operation in 78%. One patient was deemed unsuitable for a Fontan operation. There
      was 1 takedown and 1 late death after the Fontan operation. Heterotaxy syndrome
      did not affect outcome ( P  > 0.05). There was no statistical difference in the
      pre-Fontan McGoon ratio, hospital length of stay, duration of pleural drainage
      and Fontan-related adverse events between patients with a dominant right
      ventricle and those with a left ( P  > 0.05). CONCLUSIONS: A TCPC in patients
      with T21 and an FSV is associated with reproducible, satisfactory outcomes. An
      assisted-Glenn procedure with pulsatile pulmonary blood flow and a fenestrated
      Fontan may be associated with attenuated perioperative morbidity and late
      attrition.

PMID- 28453808
TI  - Long-term pulmonary function after surgery for lung cancer.
AB  - OBJECTIVES: Many patients with lung cancer have been cured by surgical
      intervention. However, the long-term effects of lung resection on pulmonary
      function are unclear. Therefore, we investigated long-term pulmonary function
      after surgery. METHODS: We retrospectively reviewed the medical records of
      patients who underwent surgery for lung cancer between 2001 and 2009. A total of
      445 patients who had survived more than 5 years since the surgery were included.
      The patients were divided into lobectomy, segmentectomy and partial resection
      groups. The time-dependent changes in pulmonary function were investigated.
      RESULTS: The percentages of the vital capacity and forced expiratory volume in 1
      second (FEV 1 ) at postoperative year (POY) 1 vs preoperative values were 92.9 +/
      11.1% and 91.3 +/- 13.0% in the lobectomy group, 95.9 +/- 9.0% and 93.8 +/-
      10.5% in the segmentectomy group and 97.8 +/- 7.3% and 98.1 +/- 8.3% in the
      partial resection group, respectively. The values in the lobectomy group were
      significantly lower than those in the segmentectomy and partial resection groups.
      The percentages of vital capacity and FEV 1 at POY 5 vs preoperative values were
      90.0 +/- 11.5% and 86.2 +/- 11.9% in the lobectomy group, 93.4 +/- 9.8% and 91.1
      +/- 9.8% in the segmentectomy group and 94.3 +/- 8.8% and 94.0 +/- 8.0% in the
      partial resection group, respectively. The decrease in the rates from POY 1 to
      POY 5 were not significantly different among the procedures. CONCLUSIONS:
      Pulmonary function declined with pulmonary resection. After the patient recovered
      from the operation, pulmonary function decreased with time regardless of the
      surgical procedure.

PMID- 28453809
TI  - In patients undergoing lung resection is it safe to administer amiodarone either
      as prophylaxis or treatment of atrial fibrillation?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was whether the administration of amiodarone is
      safe in patients undergoing lung resection either for prophylaxis or treatment of
      de novo postoperative atrial fibrillation (POAF). A total of 30 papers were
      identified, of which 13 represented the best evidence to answer the clinical
      question. The authors, journal, date, study type, country of publication, patient
      demographics, relevant outcomes and results were tabulated. Among the identified
      papers, there were 2 meta-analyses, 1 best evidence topic and 3 randomized
      studies, while the remainder were retrospective. When considering perioperative
      amiodarone for the prophylaxis of POAF, 3 randomized studies reported no
      significantly increased postoperative complications or amiodarone-related side
      effects. Mortality and length of hospital stay were similar in patients receiving
      amiodarone compared with either no amiodarone or other prophylactic
      antiarrhythmic medication. When considering amiodarone for the treatment of POAF,
      1 study reported a significantly increased incidence of ARDS after anatomical
      lung resection (P < 0.001). Two case series reported that patients developing
      POAF after lung resection and managed with amiodarone also had either none or
      acceptable rates of side effects, with no serious respiratory complications. Two
      retrospective and 1 prospective observational study reported that amiodarone used
      either for the treatment of POAF, or for prophylaxis against it, had similar
      rates of postoperative respiratory complications, length of hospital stay and
      mortality, compared with either no treatment or treatment with other prophylactic
      or therapeutic agents. In accordance with the Society of Thoracic Surgeons
      guidelines on prophylaxis and management of POAF in general thoracic surgery,
      these data suggest that amiodarone is a safe agent for the management of POAF
      after lung resection. Careful monitoring in patients treated with amiodarone
      after pneumonectomy should be considered because development of acute lung
      toxicity can increase length of hospital stay, morbidity and mortality. Further
      studies may also be needed to identify the subset of pneumonectomy patients at
      risk of pulmonary toxicity after use of amiodarone.

PMID- 28453810
TI  - eComment. The thoracic aorta as an antegrade inflow source for chronic mesenteric
      ischaemia.

PMID- 28453811
TI  - eComment. Descendo-bifemoral bypass grafting with renal revascularization for
      complex obliterative arteriopathy.

PMID- 28453812
TI  - eComment. Amiodarone-induced pulmonary toxicity in patients with atrial
      fibrillation undergoing lung resection.

PMID- 28453814
TI  - Graphene specimen support technique for low voltage STEM imaging.
AB  - The scanning transmission electron microscopy (STEM) mode of today's field
      emission scanning electron microscopes enables sub-nanometer resolution imaging.
      Graphene is a single-atom thick, electrically conductive material, making it an
      excellent specimen support for the low voltage STEM imaging of nanometer-sized
      objects such as viruses. Here we present low voltage STEM images of bacteriophage
      T4 recorded on highly cleaned graphene films. The results show that ultrathin
      graphene support films markedly improve image signal at low accelerating
      voltages. Staining with a low atomic number methylamine vanadate stain combined
      with the graphene support film enables the clear visualization of the fine
      structure of the T4 tail by the low voltage STEM technique. Despite the
      advantages of graphene support films, difficulties are often encountered in
      placing hydrophilic biological samples on hydrophobic graphene electron
      microscopy grids. We employed a spin sedimentation sample loading method to
      overcome this problem.

PMID- 28453815
TI  - Comparing docetaxel plus cisplatin versus fluorouracil plus cisplatin in
      esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy.
AB  - Objective: The optimal neoadjuvant chemoradiotherapy (CRT) regimen in esophageal
      cancer has not yet been defined. This study was aimed to compare the differences
      in pathologic response and survival between docetaxel/cisplatin and
      fluorouracil/cisplatin as neoadjuvant CRT in locally advanced esophageal squamous
      cell carcinoma (SCC). Methods: We retrospectively analyzed patients with thoracic
      esophageal SCC who received neoadjuvant CRT followed by esophagectomy from 2000
      to 2014. After adjusting for sex, age, performance status, tumor length, tumor
      location and clinical TNM stage, 32 docetaxel/cisplatin-treated patients were
      matched to 62 patients who received fluorouracil/cisplatin at a ratio of 1:2.
      Treatment toxicity, pathologic complete response (pCR) and survival outcomes were
      compared between groups. Results: Baseline characteristics were well balanced
      between groups. The pCR rate in the docetaxel/cisplatin group was higher than
      that in the fluorouracil/cisplatin group but without significant difference
      (40.6% vs. 30.6%, P = 0.333). The 3-year overall survival rate in the
      docetaxel/cisplatin group was 64.9% versus 46.0% in the fluorouracil/cisplatin
      group (P = 0.039). There were no significant differences in incidence of
      treatment toxicity during CRT or surgical complications between groups, with the
      exception of Grade 3-4 hematologic toxicity (37.5% vs. 17.7%, P = 0.035), which
      was more frequent in the docetaxel/cisplatin group. Conclusions:
      Docetaxel/cisplatin might be associated with more favorable survival than
      fluorouracil/cisplatin in esophageal SCC treated with neoadjuvant CRT.
      Prospective validation is warranted.

PMID- 28453813
TI  - Identification and allelic dissection uncover roles of lncRNAs in secondary
      growth of Populus tomentosa.
AB  - Long non-coding RNAs (lncRNAs) function in various biological processes. However,
      their roles in secondary growth of plants remain poorly understood. Here, 15,691
      lncRNAs were identified from vascular cambium, developing xylem, and mature xylem
      of Populus tomentosa with high and low biomass using RNA-seq, including 1,994
      lncRNAs that were differentially expressed (DE) among the six libraries. 3,569
      cis-regulated and 3,297 trans-regulated protein-coding genes were predicted as
      potential target genes (PTGs) of the DE lncRNAs to participate in biological
      regulation. Then, 476 and 28 lncRNAs were identified as putative targets and
      endogenous target mimics (eTMs) of Populus known microRNAs (miRNAs),
      respectively. Genome re-sequencing of 435 individuals from a natural population
      of P. tomentosa found 34,015 single nucleotide polymorphisms (SNPs) within 178
      lncRNA loci and 522 PTGs. Single-SNP associations analysis detected 2,993
      associations with 10 growth and wood-property traits under additive and dominance
      model. Epistasis analysis identified 17,656 epistatic SNP pairs, providing
      evidence for potential regulatory interactions between lncRNAs and their PTGs.
      Furthermore, a reconstructed epistatic network, representing interactions of 8
      lncRNAs and 15 PTGs, might enrich regulation roles of genes in the
      phenylpropanoid pathway. These findings may enhance our understanding of non
      coding genes in plants.

PMID- 28453816
TI  - The incidence, predictive factors and prognosis of acute pulmonary complications
      after transcatheter aortic valve implantation.
AB  - OBJECTIVES: Although acute pulmonary complications (APCs), such as the
      exacerbation of pulmonary disease (PD) or a newly developed pulmonary event, are
      thought to be catastrophic after invasive therapy, little is known about the
      occurrence of APCs after transcatheter aortic valve implantation (TAVI). This
      study aims to clarify the incidence, predictive factors and impact of APCs on
      prognosis after TAVI. METHODS: We identified 749 patients who underwent TAVI,
      using data from the Optimized CathEter vAlvular iNtervention (OCEAN-TAVI)
      Japanese multicentre registry. APCs were defined as exacerbation of a comorbidity
      or newly developed PD during hospitalization. Patients were divided into 2
      groups: an APC group (1.5%, 11/749) and a non-APC group (98.5%, 738/749).
      Clinical and prognostic outcomes were compared, and predictive factors for APCs
      were assessed. RESULTS: Procedure-related death did not differ between the groups
      (0.4% vs 0.0%, P = 1.00), although 30-day mortality was significantly higher in
      the APC group than in the non-APC group (27.3% vs 1.6%, P = 0.001) and the
      difference in cumulative 1-year mortality increased further (72.7% vs 8.6%, log
      rank test: P < 0.001). In particular, concomitant PD and transapical (TA)
      approach were identified as predictors of APCs after TAVI [univariable odds ratio
      (uOR) = 24.2, 95% confidence interval (CI) = 3.08-189.9, P = 0.002; uOR = 3.69,
      95% CI = 1.11-12.3, P = 0.033, respectively]. CONCLUSIONS: Although rare, the
      occurrence of APCs after TAVI was associated with extremely poor prognosis.
      Patients undergoing TAVI with concomitant PD and/or TA require careful
      consideration to avoid the risk of APCs.

PMID- 28453817
TI  - Epidemiology of sudden cardiac death in Cameroon: the first population-based
      cohort survey in sub-Saharan Africa.
AB  - Background: Incidence estimates of sudden cardiac death (SCD) in sub-Saharan
      Africa (SSA) are unknown. Method: Over 12 months, the household administrative
      office and health community committee within neighbourhoods in two health areas
      of Douala, Cameroon, registered all deaths among 86 188 inhabitants aged >18
      years. As part of an extended multi-source surveillance system, the Emergency
      Medical Service (EMS), local medical examiners and district hospital mortuaries
      were also surveyed. Whereas two physicians investigated every natural death, two
      cardiologists reviewed all unexpected natural deaths. Results: There were 288 all
      cause deaths and 27 (9.4%) were SCD. The crude incidence rate was 31.3 [95%
      confidence interval (CI): 20.3-40.6]/100 000 person-years. The age-standardized
      rate by the African standard population was 33.6 (95% CI: 22.4-44.9)/100 000
      person-years. Death occurred at night in 37% of cases, including 11% of patients
      who died while asleep. Out-of-hospital sudden cardiac arrest occurred in 63% of
      cases, 55.5% of which occurred at home. Of the 88.9% cases of witnessed cardiac
      arrest, 63% occurred in the presence of a family member and cardiopulmonary
      resuscitation was attempted only in 3.7%. Conclusion: The burden of SCD in this
      African population is heavy with distinct characteristics, whereas awareness of
      SCD and prompt resuscitation efforts appear suboptimal. Larger epidemiological
      studies are required in SSA in order to implement preventive measures, especially
      in women and young people.

PMID- 28453819
TI  - Evaluation of a care transition program with pharmacist-provided home-based
      medication review for elderly Singaporeans at high risk of readmissions.
AB  - Objective: This study aimed to determine whether pharmacist-provided home-based
      medication review (HBMR) can reduce readmissions in the elderly. Design:
      Retrospective cohort study. Setting: Patient's home. Participants: Records of
      patients referred to a care transition program from March 2011 through March 2015
      were reviewed. Patients aged 60 years and older taking more than 5 medications
      and had at least 2 unplanned admissions within 3 months preceding the first home
      visit were included. Intervention: Pharmacist-provided HBMR. Main outcome
      measures: Primary outcome was readmission rate over 6 months after the first home
      visit. Secondary outcomes included emergency department (ED) visits, outpatient
      visits and mortality. Drug-related problems (DRPs) were reported for the HBMR
      group. Multivariate incidence rate ratios (IRR) and hazard ratio (HR) were
      calculated with adjustments for covariates. Results: The study included 499
      patients (97 HBMR, 402 no HBMR). Pharmacist-provided HBMR reduced readmissions by
      26% (IRR = 0.74, 95% CI: 0.59-0.92, P = 0.007), reduced ED visits by 20% (IRR =
      0.80, 95% CI: 0.66-0.98, P = 0.030) and increased outpatient visits by 16% (IRR =
      1.16, 95% CI: 0.95-1.41, P = 0.150). There were 8 and 44 deaths in the HBMR and
      no HBMR groups respectively (HR = 0.73, 95% CI: 0.29-1.81, P = 0.492).
      Pharmacists identified 464 DRPs, with 169 (36.4%) resolved within 1 month after
      the home visit. Conclusions: The study suggests that pharmacist-provided HBMR is
      effective in reducing readmissions and ED visits in the elderly. More studies in
      the Asian population are needed to determine its long term benefits and patient's
      acceptability.

PMID- 28453818
TI  - Downstream element determines RNase Y cleavage of the saePQRS operon in
      Staphylococcus aureus.
AB  - In gram-positive bacteria, RNase J1, RNase J2 and RNase Y are thought to be major
      contributors to mRNA degradation and maturation. In Staphylococcus aureus, RNase
      Y activity is restricted to regulating the mRNA decay of only certain
      transcripts. Here the saePQRS operon was used as a model to analyze RNase Y
      specificity in living cells. A RNase Y cleavage site is located in an intergenic
      region between saeP and saeQ. This cleavage resulted in rapid degradation of the
      upstream fragment and stabilization of the downstream fragment. Thereby, the
      expression ratio of the different components of the operon was shifted towards
      saeRS, emphasizing the regulatory role of RNase Y activity. To assess cleavage
      specificity different regions surrounding the sae CS were cloned upstream of
      truncated gfp, and processing was analyzed in vivo using probes up- and
      downstream of CS. RNase Y cleavage was not determined by the cleavage site
      sequence. Instead a 24-bp double-stranded recognition structure was identified
      that was required to initiate cleavage 6 nt upstream. The results indicate that
      RNase Y activity is determined by secondary structure recognition determinants,
      which guide cleavage from a distance.

PMID- 28453821
TI  - Quality of antenatal care and client satisfaction in Kenya and Namibia.
AB  - Objective: Despite much progress in maternal health service coverage, the quality
      of care has not seen parallel improvement. This study assessed the quality of
      antenatal care (ANC), an entry point to the health system for many women. Design:
      The study used data from recent Service Provision Assessment (SPA) surveys of
      nationally representative health facilities in Kenya and Namibia. Setting: Kenya
      and Namibia represent the situation in much of sub-Saharan Africa, where ANC is
      relatively common but maternal mortality remains high. Participants: The SPA
      comprised an inventory of health facilities that provided ANC, interviews with
      ANC providers and clients, and observations of service delivery. Interventions:
      Not applicable. Main Outcome Measures: Quality was measured in terms of structure
      and process of service provision, and client satisfaction as the outcome of
      service provision. Results: Wide variations in structural and process attributes
      of quality of care existed in both Kenya and Namibia; however, better structural
      quality did not translate to better service delivery process or greater client
      satisfaction. Long waiting time was a common problem and was generally more
      serious in hospitals and health centers than in clinics and smaller facilities;
      it was consistently associated with lower client satisfaction. The study also
      indicates that the provider's technical preparedness may not be sufficient to
      provide good-quality services and to ensure client satisfaction. Conclusions:
      Findings highlight important program implications, including improving ANC
      services and promoting their use at health clinics and lower-level facilities,
      and ensuring that available supplies and equipment are used for service
      provision.

PMID- 28453820
TI  - Reliability of clinical impact grading by healthcare professionals of common
      prescribing error and optimisation cases in critical care patients.
AB  - Objective: To identify between and within profession-rater reliability of
      clinical impact grading for common critical care prescribing error and
      optimisation cases. To identify representative clinical impact grades for each
      individual case. Design: Electronic questionnaire. Setting: 5 UK NHS Trusts.
      Participants: 30 Critical care healthcare professionals (doctors, pharmacists and
      nurses). Intervention: Participants graded severity of clinical impact (5-point
      categorical scale) of 50 error and 55 optimisation cases. Main Outcome Measures:
      Case between and within profession-rater reliability and modal clinical impact
      grading. Methods: Between and within profession rater reliability analysis used
      linear mixed model and intraclass correlation, respectively. Results: The
      majority of error and optimisation cases (both 76%) had a modal clinical severity
      grade of moderate or higher. Error cases: doctors graded clinical impact
      significantly lower than pharmacists (-0.25; P < 0.001) and nurses (-0.53; P <
      0.001), with nurses significantly higher than pharmacists (0.28; P < 0.001).
      Optimisation cases: doctors graded clinical impact significantly lower than
      nurses and pharmacists (-0.39 and -0.5; P < 0.001, respectively). Within
      profession reliability grading was excellent for pharmacists (0.88 and 0.89; P <
      0.001) and doctors (0.79 and 0.83; P < 0.001) but only fair to good for nurses
      (0.43 and 0.74; P < 0.001), for optimisation and error cases, respectively.
      Conclusions: Representative clinical impact grades for over 100 common
      prescribing error and optimisation cases are reported for potential clinical
      practice and research application. The between professional variability
      highlights the importance of multidisciplinary perspectives in assessment of
      medication error and optimisation cases in clinical practice and research.

PMID- 28453822
TI  - Evaluation of a novel mentor program to improve surgical care for US hospitals.
AB  - Objective: To evaluate a novel mentor program for 27 US surgeons, charged with
      improving quality at their respective hospitals, having been paired 1:1 with 27
      surgeon mentors through a state-wide quality improvement (QI) initiative. Design:
      Mixed-methods utilizing quantitative surveys and in-depth semi-structured
      interviews. Setting: The Illinois Surgical Quality Improvement Collaborative
      (ISQIC) utilized a novel Mentor Program to guide surgeons new to QI.
      Participants: All mentor-mentee pairs received the survey (n = 27). Purposive
      sampling identified a subset of mentors (n = 8) and mentees (n = 4) for in-depth
      semi-structured interviews. Intervention: Surgeons with expertise in QI mentored
      surgeons new to QI. Main outcome measures: (i) Quantitative: self-reported
      satisfaction with the mentor program; (ii) Qualitative: key themes suggesting
      actions and strategies to facilitate mentorship in QI. Results: Mentees expressed
      satisfaction with the mentor program (n = 24, 88.9%) and agreed that mentorship
      is vital to ISQIC (n = 24, 88.9%). Analysis of interview data revealed four key
      themes: (i) nuances of data management, (ii) culture of quality and safety, (iii)
      mentor-mentee relationship and (iv) logistics. Strategies from these key themes
      include: utilize raw data for in-depth QI understanding, facilitate presentations
      to build QI support, identify opportunities for in-person meetings and establish
      scheduled conference calls. The mentor's role required sharing experiences and
      acting as a resource. The mentee's role required actively bringing questions and
      identifying barriers. Conclusions: Mentorship plays a vital role in advancing
      surgeon knowledge and engagement with QI in ISQIC. Key themes in mentorship
      reflect strategies to best facilitate mentorship, which may serve as a guide to
      other collaboratives.

PMID- 28453823
TI  - A flowchart for building evidence-based care bundles in intensive care: based on
      a systematic review.
AB  - Purpose: The Institute for Healthcare Improvement is the founder of the care
      bundled approach and described the methods used on how to develop care bundles.
      However, other useful methods are published as well. In this systematic review,
      we identified what different methods were used to design care bundles in
      intensive care units. The results were used to build a comprehensive flowchart to
      guide through the care bundle design process. Data sources: Electronic databases
      were searched for eligible studies in PubMed, EMBASE and CINAHL from January 2001
      to August 2014. Study selection: There were no restrictions on the types of study
      design eligible for inclusion. Methodological quality was assessed by using the
      Downs & Black-checklist or Appraisal of Guidelines, REsearch and Evaluation II.
      Data extraction: Data extraction was independently performed by two reviewers.
      Results of data synthesis: A total of 4665 records were screened and 18 studies
      were finally included. The complete process of designing bundles was reported in
      33% (6/18). In 50% (9/18), one of the process steps was described. A narrative
      report was written about care bundles in general in 17% (3/18). We built a
      comprehensive flowchart to visualize and structure the process of designing care
      bundles. Conclusion: We identified useful methods for designing evidence-based
      care bundles. We built a comprehensive flowchart to provide an overview of the
      methods used to design care bundles so that others could choose their own
      applicable method. It guides through all necessary steps in the process of
      designing care bundles.

PMID- 28453824
TI  - Professional attitudes toward incident reporting: can we measure and compare
      improvements in patient safety culture?
AB  - Objective: To establish categories of professionals' attitudes toward incident
      reporting by analyzing the trends in incident reporting while accounting for
      general risk indicators. Design: The incident reporting system was evaluated over
      6 years. Reporting rates, stratified by year and profession, were estimated using
      the non-mandatory reported events/full-time equivalent (NM-IR/FTE) rate. Other
      indicators were collected using the hospital's official database. Staff attitudes
      toward self-reporting were analyzed. Univariate and multivariable analyses were
      performed. Setting: A 1000-bed Italian academic hospital. Participants: Staff of
      the hospital (over 3200 professionals). Interventions: None. Main outcome
      measures: NM-IT/FTE rates, self-reported rates, patient complaints/praises, work
      accidents among professionals and 30-day readmissions. Results: The overall
      reporting rate was 0.44 (95% confidence interval [CI]: 0.42-0.46) among doctors
      and 0.40 (95% CI: 0.39-0.41) among nurses. Between 2010 and 2015, only the
      doctors' reporting rate increased significantly (P = 0.04), from 0.29 (95% CI:
      0.25-0.34) to 0.67 (95% CI: 0.60-0.73). Patient complaints decreased from 384 to
      224 (P < 0.001) and work accidents decreased from 296 to 235 (P = 0.01), while
      other indicators remained constant. Multivariable logistic regression showed that
      self-reporting was more likely among nurses than doctors (odds ratio: 1.51; 95%
      CI: 1.31-1.73) and for severe events than near misses (odds ratio: 1.78; 95% CI:
      1.11-2.87). Conclusions: Because the doctors' reporting rates increased during
      the study period, doctors may be more likely to report adverse events than
      nurses, although nurses reported more events. Incident reporting trends and other
      routinely collected risk indicators may be useful to improve our understanding
      and measurement of patient safety issues.

PMID- 28453825
TI  - Leveraging the full value and impact of accreditation.
AB  - Providing high quality and safe patient care is a challenge in the current
      rapidly changing and complex health care environment. A variety of independent
      tools and methodologies contribute to this effort, e.g. regulatory requirements,
      quality improvement tools and accreditation methodologies. A concern is that each
      alone will not achieve the tipping point in health care quality that is required.
      This paper suggests that the methodology and application of accreditation have
      the potential to be the force to bring these approaches into alignment and
      ultimately measurably improve the quality of care.

PMID- 28453826
TI  - Unplanned readmissions within 30 days after discharge: improving quality through
      easy prediction.
AB  - Objective: To propose an easy predictive model for the risk of rehospitalization,
      built from hospital administrative data, in order to prevent repeated admissions
      and to improve transitional care. Design: Retrospective cohort study. Setting:
      Azienda Ospedaliero Universitaria Pisana (Pisa University Hospital).
      Participants: Patients residing in the territory of the province of Pisa (Tuscany
      Region) with at least one unplanned hospital admission leading to a medical
      Diagnosis-Related Group (DRG) in the calendar year 2012. Intervention: We
      compared two groups of patients: patients coded as 'RA30' (readmitted within 30
      days after the previous discharge) and patients coded as 'NRA30' (either admitted
      only once or readmitted after 30 days since the latest discharge). Main Outcome
      Measures: The effect of age, sex, length of stay, number of diagnoses, normalized
      number of admissions and presence of diseases on the probability of
      rehospitalization within 30 days after discharge was evaluated. Results: The
      significant variables included in the predictive model were: age, odds ratio (OR)
      = 1.018, 95% confidence interval (CI) = 1.011-1.026; normalized number of
      admissions, OR = 1.257, CI = 1.225-1.290; number of diagnoses, OR = 1.306, CI =
      1.174-1.452 and presence of cancer diagnosis, OR = 1.479, CI = 1.088-2.011.
      Conclusions: The model can be easily applied when discharging patients who have
      been hospitalized after an access to the Emergency Department to predict the risk
      of rehospitalization within 30 days. The prediction can be used to activate
      focused hospital-primary care transitional interventions. The model has to be
      validated first in order to be implemented in clinical practice.

PMID- 28453828
TI  - Examining the nature of interprofessional interventions designed to promote
      patient safety: a narrative review.
AB  - Purpose: This narrative review aimed to scope the patient safety literature to
      identify interprofessional intervention approaches, sources of evidence and
      reported outcomes. Data sources: Two major databases (MEDLINE and CINAHL) were
      searched from 2005 to 2015. Study selection: A total of 1552 abstracts were
      initially identified. After screening these abstracts, 129 full papers were
      obtained. Further screening resulted in a total of 89 papers included in this
      review. Data extraction: The following information was extracted from each
      included paper: details on the patient safety intervention, study methods
      employed and outcomes reported. Results of data synthesis: It was found that the
      bulk of the included studies was undertaken in a North American acute care
      context. Most often, studies involved qualified professionals from nursing and
      medicine collaborating in hospitals and medical centres. Nearly half the studies
      reported in this review employed educational interventions, such as TeamSTEPPS,
      aimed at enhancing practitioners' competence of delivering safe patient care.
      Nearly a third of studies involved practice-based interventions (e.g. checklists)
      aimed at improving the delivery of safe care. Most of the studies used a quasi
      experimental design and typically gathered survey data. The majority reported
      outcomes related to changes in professionals' attitudes, knowledge and skills.
      There were, however, fewer studies reporting changes in practitioners' safety
      behaviours, organizational practices or patient benefit. Conclusion: The use of
      different interprofessional interventions are key activities involved in
      promoting safe patient care practices. However, further work is needed to
      strengthen these interventions and their evaluations.

PMID- 28453827
TI  - Factors constraining patient engagement in implantable medical device discussions
      and decisions: interviews with physicians.
AB  - Objective: Patient engagement (PE) is warranted when treatment risks and outcomes
      are uncertain, as is the case for higher risk medical devices. Previous research
      found that patients were not engaged in discussions or decisions about
      implantable medical devices. This study explored physician views about engaging
      patients in such discussions. Design: Qualitative interviews using a basic
      descriptive approach. Setting: Canada. Participants: Practicing cardiovascular
      and orthopaedic physicians. Main outcome measures: Level, processes and
      determinants of PE in medical device discussions and decisions. Results: Views
      were largely similar among 10 cardiovascular and 12 orthopaedic physicians
      interviewed. Most said that it was feasible to inform and sometimes involve
      patients in discussions, but not to partner with them in medical device decision
      making. PE was constrained by patient (comfort with PE, technical understanding,
      physiologic/demographic characteristics, prognosis), physician (device
      preferences, time), health system (purchasing contracts) and device factors
      (number of devices on market, comparative advantage). A framework was generated
      to help physicians engage patients in discussions about medical devices, even
      when decisions may not be preference sensitive due to multiple constraints on
      choice. Conclusions: This study identified that patients are not engaged in
      discussions or decisions about implantable medical devices. This may be due to
      multiple constraints. Further research should establish the legitimacy,
      prevalence and impact of constraining factors, and examine whether and how
      different levels and forms of PE are needed and feasible.

PMID- 28453829
TI  - Experimenting the hospital survey on patient safety culture in prevention
      facilities in Italy: psychometric properties.
AB  - Objective: The Agency for Healthcare Research and Quality Hospital Survey on
      Patient Safety Culture (HSOPS) was designed to assess staff views on patient
      safety culture in hospital. This study examines psychometrics of the Italian
      translation of the HSOPS for use in territorial prevention facilities. Design:
      After minimal adjustments and pre-test of the Italian version, a qualitative
      cross-sectional study was carried out. Setting: Departments of Prevention (DPs)
      of four Local Health Authorities in Northern Italy. Participants: Census of
      medical and non-medical staff (n. 479). Intervention: Web-based self-administered
      questionnaire. Main outcome measures: Descriptive statistics, internal
      reliability, Confirmatory Factor Analysis (CFA) and intercorrelations among
      survey composites. Results: Initial CFA of the 12 patient safety culture
      composites and 42 items included in the original version of the questionnaire
      revealed that two dimensions (Staffing and Overall Perception of Patient Safety)
      and nine individual items did not perform well among Italian territorial
      Prevention staff. After dropping those composites and items, psychometric
      properties were acceptable (comparative fit index = 0.94; root mean square error
      of approximation = 0.04; standardized root mean square residual = 0.04). Internal
      consistency for each remaining composite met or exceeded the criterion 0.70.
      Intercorrelations were all statistically significant. Conclusions: Psychometric
      analyses provided overall support for 10 of the 12 initial patient safety culture
      composites and 33 of the 42 initial composite items. Although the original
      instrument was intended for US Hospitals, the Italian translation of the HSOPS
      adapted for use in territorial prevention facilities performed adequately in
      Italian DPs.

PMID- 28453830
TI  - Patient's satisfaction and incentive programs for physicians.

PMID- 28453832
TI  - Study of Residual TL of CaSO4:Dy-based Thermoluminescence Dosemeter.
AB  - Thermoluminescence (TL) signal obtained during second readout of a TL dosemeter
      disc previously exposed to ionising radiation is termed as residual TL. The
      origin of residual TL has not been discussed in detail so far in the literature.
      In this work, experimentally obtained residual TL signal and its origin is
      studied for CaSO4:Dy-based TL dosemeter through numerical simulation and role of
      deeper traps has been discussed.

PMID- 28453831
TI  - Sortilin 1 Loss-of-Function Protects Against Cholestatic Liver Injury by
      Attenuating Hepatic Bile Acid Accumulation in Bile Duct Ligated Mice.
AB  - Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein
      sorting in the endocytic or secretory pathways. Recent studies revealed a role of
      Sort1 in the regulation of cholesterol and bile acid (BA) metabolism. This study
      further investigated the role of Sort1 in modulating BA detoxification and
      cholestatic liver injury in bile duct ligated mice. We found that Sort1 knockout
      (KO) mice had attenuated liver injury 24 h after bile duct ligation (BDL), which
      was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice
      had about 20% larger BA pool size than sham-operated wildtype (WT) mice, but 24 h
      after BDL Sort1 KO mice had significantly attenuated hepatic BA accumulation and
      smaller BA pool size. After 14 days BDL, Sort1 KO mice showed significantly lower
      hepatic BA concentration and reduced expression of inflammatory and fibrotic
      marker genes, but similar degree of liver fibrosis compared with WT mice.
      Unbiased quantitative proteomics revealed that Sort1 KO mice had increased
      hepatic BA sulfotransferase 2A1, but unaltered phase-I BA metabolizing cytochrome
      P450s or phase-III BA efflux transporters. Consistently, Sort1 KO mice showed
      elevated plasma sulfated taurocholate after BDL. Finally, we found that liver
      Sort1 was repressed after BDL, which may be due to BA activation of farnesoid x
      receptor. In conclusion, we report a role of Sort1 in the regulation of hepatic
      BA detoxification and cholestatic liver injury in mice. The mechanisms underlying
      increased hepatic BA elimination in Sort1 KO mice after BDL require further
      investigation.

PMID- 28453833
TI  - Vaccination to Reduce Reactivation of Herpes Simplex Virus Type 2.

PMID- 28453834
TI  - Overproduction of Outer Membrane Protein A by Acinetobacter baumannii as a Risk
      Factor for Nosocomial Pneumonia, Bacteremia, and Mortality Rate Increase.
AB  - Background: Outer membrane protein A (OmpA) is a porin involved in Acinetobacter
      baumannii pathogenesis. However, OmpA clinical implication in hospital-acquired
      infections remains unknown. We aimed to determine whether OmpA overproduction was
      a risk factor associated with pneumonia, bacteremia, and mortality. Methods: We
      analyzed demographic, microbiological, and clinical data from 100 patients
      included in a unicenter cohort and 246 included in a unicenter cohort and a
      multicenter cohort. Representative isolates were classified into 2 groups: (1)
      isolates from patients colonized by A. baumannii (16 from the unicenter and 20
      from the multicenter cohort) and (2) isolates from bacteremic or nonbacteremic
      patients with pneumonia (PP) caused by A. baumannii (13 from the unicenter and 23
      from the multicenter cohort) Expression of ompA was determined with quantitative
      reverse-transcription polymerase chain reaction. Results: Isolates from PP
      overexpressed more ompA than those from colonized patients from the unicenter
      (ratio, 1.76 vs 0.36; P < .001) and the multicenter (1.36 vs 0.91; P = .03)
      cohorts. Among isolates from PP, those from bacteremic patients overexpressed
      nonsignificantly more ompA than those from nonbacteremic patients in the
      unicenter (ratio, 2.37 vs 1.43; P = .06) and the multicenter (2.03 vs 0.91; P =
      .14) cohorts. Multivariate analysis in both cohorts together showed ompA
      overexpression as independent risk factor for pneumonia (P < .001), bacteremia (P
      = .005), and death (P = .049). Conclusions: These data suggest that ompA
      overexpression is an associated factor for pneumonia, bacteremia, and death due
      to A. baumannii.

PMID- 28453835
TI  - Herpes Simplex Virus Type 2 Acquisition Among HIV-1-Infected Adults Treated With
      Tenofovir Disoproxyl Fumarate as Part of Combination Antiretroviral Therapy:
      Results From the ACTG A5175 PEARLS Study.
AB  - Objective: Tenofovir disoproxyl fumarate (TDF) disoproxyl fumarate (TDF) has in
      vitro activity against herpes simplex virus type 2 (HSV-2) and reduced HSV-2
      acquisition as preexposure prophylaxis. Whether TDF-containing antiretroviral
      therapy (ART) reduces HSV-2 acquisition is unknown. Design: Secondary analysis of
      AIDS Clinical Trials Group A5175, a randomized, open-label study of 3 ART
      regimens among 1571 participants. Methods: HSV-2 serostatus was assessed at
      baseline, at study exit, and before a change in ART regimen. Results: Of 365 HSV
      2-seronegative persons, 68 acquired HSV-2, with 24 receiving TDF-containing ART
      and 44 receiving ART without TDF (HSV-2 seroconversion incidence, 6.42 and 6.63
      cases/100 person-years, respectively; hazard ratio, 0.89; 95% confidence
      interval, .55-1.44). Conclusions: HSV-2 acquisition was not reduced in HIV
      infected, HSV-2-uninfected persons during TDF-containing ART.

PMID- 28453836
TI  - Commonly Transmitted HIV-1 Drug Resistance Mutations in Reverse-Transcriptase and
      Protease in Antiretroviral Treatment-Naive Patients and Response to Regimens
      Containing Tenofovir Disoproxil Fumarate or Tenofovir Alafenamide.
AB  - Background: The presence of transmitted drug resistance mutations (TDRMs) in
      antiretroviral treatment (ART)-naive patients can adversely affect the outcome of
      ART. Methods: Resistance testing was conducted in 6704 ART-naive subjects
      predominantly from the United States and Europe in 9 clinical studies conducted
      by Gilead Sciences from 2000 to 2013. Results: The presence of TDRMs increased
      during this period (from 5.2% to 11.4%), primarily driven by an increase in
      nonnucleoside reverse-transcriptase (RT) inhibitor (NNRTI) resistance mutations
      (from 0.3% to 7.1%), particularly K103N/S (increase from 0.3% to 5.3%).
      Nucleoside/nucleotide RT inhibitor mutations were found in 3.1% of patients. Only
      1 patient had K65R (0.01%) and 7 had M184V/I (0.1%), despite high use of
      tenofovir disoproxil fumarate (TDF), emtricitabine, and lamivudine and potential
      transmission of resistance to these drugs. At least 1 thymidine-analogue
      mutations was present in 2.7% of patients with 0.07% harboring T215Y/F and 2.7%
      harboring T215 revertant mutations (T215rev). Patients with the combination of
      M41L + L210W + T215rev showed full human immunodeficiency virus RNA suppression
      while receiving a TDF- or tenofovir alafenamide-containing regimen. Conclusions:
      There was an overall increase of TDRMs among patients enrolling in clinical
      trials from 2000 through 2013, driven primarily by an increase in NNRTI
      resistance. However, the presence of common TDRMs, including thymidine-analogue
      mutations/T215rev, showed no impact on response to TDF- or tenofovir alafenamide
      containing regimens.

PMID- 28453837
TI  - Borrelia burgdorferi BBI39 Paralogs, Targets of Protective Immunity, Reduce
      Pathogen Persistence Either in Hosts or in the Vector.
AB  - Borrelia burgdorferi genome harbors several paralogous gene families (pgf) that
      can encode immunogenic proteins of unknown function. Protein-protein interaction
      assays using a transmission-blocking vaccine candidate, BBA52, as bait identified
      an interacting partner in spirochetes-a member of pgf 54, annotated as BBI39. We
      show that BBI39 is a surface-exposed membrane antigen that is immunogenic during
      spirochete infection, despite the gene being primarily transcribed in the vector
      with a transient expression in the host only at tick-bite sites. Immunization of
      rodents with BBI39, or a diverse paralog, BBI36, or their combination impaired
      pathogen acquisition by the vector, transmission from ticks to hosts, or
      induction of disease. High-titer BBI39 immunoglobulin G antibodies, which have
      borreliacidal properties, could be generated through routine subcutaneous or oral
      immunization, further highlighting use of BBI39 proteins as novel Lyme disease
      vaccines that can target pathogens in the host or in ticks.

PMID- 28453839
TI  - Virucidal Activity of World Health Organization-Recommended Formulations Against
      Enveloped Viruses, Including Zika, Ebola, and Emerging Coronaviruses.
AB  - The World Health Organization (WHO) published 2 alcohol-based formulations to be
      used in healthcare settings and for outbreak-associated infections, but
      inactivation efficacies of these products have not been determined against (re
      )emerging viruses. In this study, we evaluated the virucidal activity of these
      WHO products in a comparative analysis. Zika virus (ZIKV), Ebola virus (EBOV),
      severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East
      respiratory syndrome coronavirus (MERS-CoV) as (re-)emerging viral pathogens and
      other enveloped viruses could be efficiently inactivated by both WHO
      formulations, implicating their use in healthcare systems and viral outbreak
      situations.

PMID- 28453838
TI  - Impact of Pre-exposure History and Host Genetics on Antibody Avidity Following
      Norovirus Vaccination.
AB  - Background: Development of high avidity, broadly neutralizing antibodies (Abs) is
      a priority after vaccination against rapidly evolving, widely disseminated
      viruses like human norovirus. After vaccination with a multivalent GI.1 and
      GII.4c norovirus virus-like particle (VLP) vaccine candidate adjuvanted with alum
      and monophosphoryl lipid A (MPL), blockade Ab titers peaked early, with no
      increase in titer following a second vaccine dose. Methods: Blockade Ab relative
      avidity was evaluated by measuring the slope of blockade Ab neutralization
      curves. Results: Blockade Ab avidity to the GI.1 vaccine component peaked at day
      35 (7 days after dose 2). Avidities to heterotypic genogroup I VLPs were not
      sustained at day 35 after vaccination or GI.1 infection, as measured from
      archived sera. Only secretor-positive participants maintained high avidity
      blockade Ab to GI.1 at day 180. Avidity to the GII.4c vaccine component peaked at
      day 7, remained elevated through day 180, and was not secretor dependent. Avidity
      to an immunologically novel GII.4 strain VLP correlated with preexisting Ab titer
      to an ancestral strain Epitope A. Conclusions: Host genetics and pre-exposure
      history shape norovirus vaccine Ab responses, including blockade Ab avidity.
      Avidity of potentially neutralizing Ab may be an important metric for evaluating
      vaccine responses to highly penetrant viruses with cross-reactive serotypes.

PMID- 28453840
TI  - Modulation of the Host Environment by Human Cytomegalovirus with Viral
      Interleukin 10 in Peripheral Blood.
AB  - Background: Human cytomegalovirus (HCMV) is a herpesvirus with both lytic and
      latent life cycles. Human cytomegalovirus encodes 2 viral cytokines that are
      orthologs of human cellular interleukin 10 (cIL-10). Both cytomegalovirus
      interleukin 10 (cmvIL-10) and Latency-associated cytomegalovirus interleukin 10
      (LAcmvIL-10) (collectively vIL-10) are expressed during lytic infection and cause
      immunosuppressive effects that impede virus clearance. LAcmvIL-10 is also
      expressed during latent infection of myeloid progenitor cells and monocytes and
      facilitates persistence. Here, we investigated whether vIL-10 could be detected
      during natural infection. Methods: Plasma from healthy blood donors was tested by
      enzyme-linked immunosorbent assay for anti-HCMV immunoglobulin G and
      immunoglobulin M and for cIL-10 and vIL-10 levels using a novel vIL-10 assay that
      detects cmvIL-10 and LAcmvIL-10, with no cross-reactivity to cIL-10. Results: vIL
      10 was evident in HCMV+ donors (n = 19 of 26), at levels ranging 31-547 pg/mL. By
      comparison, cIL-10 was detected at lower levels ranging 3-69 pg/mL. There was a
      strong correlation between vIL-10 and cIL-10 levels (P = .01). Antibodies against
      vIL-10 were also detected and neutralized vIL-10 activity. Conclusions: vIL-10
      was detected in peripheral blood of healthy blood donors. These findings suggest
      that vIL-10 may play a key role in sensing or modifying the host environment
      during latency and, therefore, may be a potential target for intervention
      strategies.

PMID- 28453841
TI  - The Use of Quinacrine in Nitroimidazole-resistant Giardia Duodenalis: An Old Drug
      for an Emerging Problem.
AB  - Background: There is little evidence regarding the management of refractory
      giardiasis after treatment with nitroimidazoles. This study estimates the
      proportion of persistent giardiasis in 3 hospitals in Barcelona, describes
      associated risk factors and genotype, and evaluates the efficacy rate of
      quinacrine in those with persistent giardiasis. Methods: A clinical, prospective,
      observational study was conducted in patients with giardiasis treated with
      nitroimidazoles. Those with persistent giardiasis were provided quinacrine.
      Molecular characterization of Giardia isolates was performed by polymerase chain
      reaction amplification of a fragment of tpi and bg genes. Results: Seventy-seven
      patients were recruited and treated with nitroimidazoles, and in 14 of 71 (20%)
      of patients followed up, Giardia persisted. Refractory giardiasis was associated
      with malaise (P = .007) and anorexia (P = .02), with previous giardiasis (P =
      .03), and with previous antibiotic (P = .02) or antiparasitic(P = .04) use.
      Quinacrine had an effectiveness rate of 100% in refractory giardiasis (n = 13;
      95% confidence interval = 75-100). Molecular characterization showed that 17
      (25%) Giardia isolates belonged to assemblage A, and 31 (43%) belonged to
      assemblage B. In refractory giardiasis, assemblage A and B were found responsible
      in 4 and 6 cases, respectively. Conclusions: Almost 20% of patients presented
      persistent giardiasis, belonging to both assemblages A and B, after
      nitroimidazole. Short course of quinacrine was effective in treating refractory
      cases. Further controlled studies should evaluate its efficacy and safety.

PMID- 28453842
TI  - A Cluster of Fatal Tick-borne Encephalitis Virus Infection in Organ Transplant
      Setting.
AB  - Background: Tick-borne encephalitis virus (TBEV) infection has become a major
      health problem in Europe and is currently a common cause of viral brain infection
      in many countries. Encephalitis in transplant recipients, althrough rare, is
      becoming a recognized complication. Our study provides the first description of
      transmission of TBEV through transplantation of solid organs. Methods: Three
      patients who received solid organ transplants from a single donor (2 received
      kidney, and 1 received liver) developed encephalitis 17-49 days after
      transplantation and subsequently died. Blood and autopsy tissue samples were
      tested by next-generation sequencing (NGS) and reverse transcription polymerase
      chain reaction (RT-PCR). Results: All 3 recipients were first analyzed in autopsy
      brain tissue samples and/or cerebrospinal fluid by NGS, which yielded 24-52
      million sequences per sample and 9-988 matched TBEV sequences in each patient.
      The presence of TBEV was confirmed by RT-PCR in all recipients and in the donor,
      and direct sequencing of amplification products corroborated the presence of the
      same viral strain. Conclusions: We demonstrated transmission of TBEV by
      transplantation of solid organs. In such a setting, TBEV infection may be fatal,
      probably due to pharmacological immunosuppression. Organ donors should be
      screened for TBEV when coming from or visiting endemic areas.

PMID- 28453843
TI  - Inflammation and Immune Activation in Antiretroviral-Treated Human
      Immunodeficiency Virus Type 1-Infected African Infants and Rotavirus Vaccine
      Responses.
AB  - Biomarkers of inflammation and immune activation were correlated with rotavirus
      vaccine responses in 68 human immunodeficiency virus type 1 (HIV-1)-infected (and
      116 HIV-exposed but uninfected (HEU) African infants receiving pentavalent
      rotavirus vaccine (RV5) in a clinical trial. Prevaccination, HIV-1+ infants had
      significantly higher concentrations of interferon gamma (IFNgamma),
      interleukin1beta, interleukin 2, interleukin 6, interleukin 10 (IL-10), and
      soluble CD14 compared with HEU infants. Postvaccination concentrations of
      neutralizing antibodies to RV5 were negatively correlated with prevaccination
      concentrations of IL-10 (RV5 surface proteins G1 and P1) and IFNgamma (G1) in the
      HIV-1+ infants, whereas antirotavirus immunoglobulin A (IgA) levels were not.
      Heightened inflammation and immune activation in HIV-1+ infants did not alter IgA
      responses associated with protection from rotavirus disease.

PMID- 28453844
TI  - Association of Endothelial Glycocalyx and Tight and Adherens Junctions With
      Severity of Plasma Leakage in Dengue Infection.
AB  - Background: The role of vascular endothelial (VE) components in dengue infection
      with plasma leakage is unknown. Therefore, we conducted a study to determine the
      adjusted association of the endothelial glycocalyx layer (EGL) and tight and
      adherens junction markers with plasma leakage. Methods: A prospective
      observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan
      Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on
      the third day of fever from November 2013 through August 2015 were included in
      the study. Multiple regression analysis was used to determine the adjusted
      association of the VE biomarkers with the severity of the plasma leakage.
      Results: A total of 103 dengue-infected patients participated in the study. In
      the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence
      interval [CI] = 1.001-1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025
      1.307) had an adjusted association with plasma leakage, whereas levels of
      syndecan-1 (OR = 1.004; 95% CI = 1.000-1.008) and claudin-5 (OR = 1.038; 95% CI =
      1.004-1.074) had an adjusted association with severe plasma leakage. Conclusions:
      In dengue-infected patients, elevated levels of syndecan-1 and chondroitin
      sulfate are strongly associated with plasma leakage, and elevated levels of
      syndecan-1 and claudin-5 are strongly associated with severe plasma leakage.

PMID- 28453845
TI  - Effect of Repeated Vaccination With the Same Vaccine Component Against 2009
      Pandemic Influenza A(H1N1) Virus.
AB  - Background: The 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) vaccine component
      has remained unchanged from 2009. We estimate the effectiveness of current and
      prior inactivated influenza A(H1N1)pdm09 vaccination from influenza seasons 2010
      2011 to 2015-2016. Methods: Patients attended with influenza-like illness were
      tested for influenza. Four periods with continued A(H1N1)pdm09 circulation were
      included in a test-negative design. Results: We enrolled 1278 cases and 2343
      controls. As compared to individuals never vaccinated against influenza
      A(H1N1)pdm09, the highest effectiveness (66%; 95% confidence interval, 49%-78%)
      was observed in those vaccinated in the current season who had received 1-2 prior
      doses. The effectiveness was not statistically lower in individuals vaccinated in
      the current season only (52%) or in those without current vaccination and >2
      prior doses (47%). However, the protection was lower in individuals vaccinated in
      the current season after >2 prior doses (38%; P = .009) or those currently
      unvaccinated with 1-2 prior doses (10%; P < .001). Current-season vaccination
      improved the effect in individuals with 1-2 prior doses and did not modify
      significantly the risk of influenza in individuals with >2 prior doses.
      Conclusion: Current vaccination or several prior doses were needed for high
      protection. Despite the decreasing effect of repeated vaccination, current-season
      vaccination was not inferior to no current-season vaccination.

PMID- 28453846
TI  - No Interactive Effects of Sex and Persistent Cytomegalovirus on Immune Phenotypes
      in Young Children: The Generation R Study.
AB  - Persistent infections with cytomegalovirus (CMV) differentially affect the host
      immune phenotype in middle-aged males and females. Because CMV already impacts on
      T-cell memory at a young age, we studied whether these effects were modified by
      sex in 1,079 children with an average age of 6 years. Sex and CMV independently
      impacted on multiple B-cell and T-cell subsets. However, there was no significant
      effect of their interaction. Importantly, the effects of sex and CMV were in part
      explained by age and infection with other herpesviruses. Thus, immune aging is
      likely to be more complex, with involvement of hormonal changes with age,
      socioeconomic status, birth characteristics, and pathogen exposure.

PMID- 28453847
TI  - Human Immunodeficiency Virus Persistence and T-Cell Activation in Blood, Rectal,
      and Lymph Node Tissue in Human Immunodeficiency Virus-Infected Individuals
      Receiving Suppressive Antiretroviral Therapy.
AB  - Background: Immune activation and inflammation remain elevated in human
      immunodeficiency virus (HIV)-infected individuals receiving antiretroviral
      therapy (ART) and may contribute to HIV persistence. Methods: Using flow
      cytometry expression of CD38, HLA-DR and PD-1 were measured in blood (n = 48),
      lymph node (LN; n = 9), and rectal tissue (n = 17) from virally suppressed
      individuals. Total and integrated HIV DNA, 2-LTR circles, and cell-associated
      unspliced HIV RNA were quantified. Results: CD4+ T cells from rectal tissue had a
      higher frequency of integrated HIV DNA compared with blood (4.26 fold-change in
      DNA; 95% confidence interval [CI] = 2.61-7.00; P < .001) and LN (2.32 fold-change
      in DNA; 95% CI = 1.22-4.41; P = .01). In rectal tissue, there were positive
      associations between integrated HIV DNA with PD-1+ CD4+ T-cells (1.44 fold-change
      in integrated HIV DNA per 10-unit increase in PD-1+ CD4+ T cells; 95% CI = 1.01
      2.05; P = .045) and CD38+HLA-DR+ CD8+ T cells (1.40 fold-change in integrated HIV
      DNA per 1-unit increase in CD38+HLA-DR+ CD8+ T cells; 95% CI = 1.05-1.86; P =
      .02). Both associations were independent of current and nadir CD4+ T-cell counts.
      Conclusions: During ART, rectal tissue is an important reservoir for HIV
      persistence with a high frequency of activated CD4+ and CD8+ T cells. PD-1 may
      represent a marker of HIV persistence in rectal tissue.

PMID- 28453849
TI  - Association Between Frailty and Components of the Frailty Phenotype With
      Modifiable Risk Factors and Antiretroviral Therapy.
AB  - The impact of antiretroviral therapy (ART) on frailty among human
      immunodeficiency virus (HIV)-infected adults has not been well described. HIV
      infected participants aged >=40 years with initial ART receipt through a
      randomized, controlled AIDS Clinical Trials Group trial completed a frailty
      assessment. Ordinal logistic regression models examined factors associated with
      frailty. Of 1016 participants, 6% were frail, and 38% were prefrail. Frailty was
      associated with lower education, older age, Medicare/Medicaid, initial efavirenz,
      smoking, obesity, and neurocognitive impairment; physical activity and alcohol
      use were protective. The associations with ART require further investigation, and
      associations between frailty and modifiable factors provide targets for future
      interventions.

PMID- 28453848
TI  - Association of the Emergence of Acyclovir-Resistant Herpes Simplex Virus Type 1
      With Prognosis in Hematopoietic Stem Cell Transplantation Patients.
AB  - Background: Antiviral-resistant herpes simplex virus type 1 (HSV-1) has been
      recognized as an emerging clinical problem among patients undergoing
      hematopoietic stem cell transplantation (HSCT). Methods: A prospective
      observational study was conducted at a hematological center over a 2-year period.
      Oropharyngeal swab samples were serially collected each week from 1 week before
      and up to 100 days after HSCT and were tested for virus isolation. The HSV-1
      isolates were tested for sensitivity to acyclovir (ACV). The prognosis of
      patients with ACV-resistant (ACVr) HSV-1 and the genetic background of the ACVr
      HSV-1 isolates were assessed. Results: Herpes simplex virus type 1 was isolated
      in 39 of 268 (15%) HSCT patients within 100 days after transplantation. Acyclovir
      resistant HSV-1 emerged in 11 of these 39 patients (28%). The 100-day death rates
      of HSCT patients without HSV-1 shedding, those with only ACV-sensitive HSV-1
      shedding, and those with ACVr HSV-1 shedding were 31%, 39%, and 64%,
      respectively. Patients with HSV-1, including ACVr HSV-1, shedding showed a
      significantly higher mortality rate. Relapsed malignancies were a significant
      risk factor for the emergence of ACVr HSV-1. Acyclovir resistance was
      attributable to viral thymidine kinase and DNA polymerase mutations in 6 and 5
      patients, respectively. Conclusions: Herpes simplex virus type 1, including ACVr
      HSV-1, shedding was associated with poorer outcome in HSCT patients, even if HSV
      disease did not always occur. Patients with relapsed malignancies were at
      especially high risk for the emergence of ACVr HSV-1.

PMID- 28453850
TI  - A Novel Ligand of Toll-like Receptor 4 From the Sheath of Wuchereria bancrofti
      Microfilaria Induces Proinflammatory Response in Macrophages.
AB  - Background: Lymphatic filariasis, frequently caused from Wuchereria bancrofti
      infection, is endemic in several parts of the globe and responsible for human
      health problems and socioeconomic loss to a large extent. Inflammatory
      consequences originating from host-parasite interaction play a major role in the
      disease pathology and allied complications. The identity of the key mediator of
      this process is yet unknown in filarial research. Methods: Microfilarial protein
      (MfP) was isolated from the sheath of W. bancrofti microfilariae through
      ultrafiltration, followed by chromatographic separation. Expression of signaling
      molecules was studied by enzyme-linked immunosorbent assay and immunoblotting.
      Binding of MfP to Toll-like receptor 4 (TLR4) was determined by co
      immunoprecipitation, fluorescein isothiocyanate-probing, and surface plasmon
      resonance analysis. Results: We found that MfP (approximately 70 kDa) binds to
      macrophage-TLR4 and triggers nuclear factor kappa beta activation that
      upregulates secretion of proinflammatory cytokines. Microfilarial protein failed
      to induce inflammation in either TLRKO macrophage or macrophage treated with TLR4
      inhibitor, indicating that MfP acts through TLR4. We have also detected
      phenotypic transformation of macrophages from anti-inflammatory (M2) to
      proinflammatory (M1) subtype after incubation with MfP. Conclusions:
      Microfilarial protein appears to be a new ligand of TLR4 from W. bancrofti.
      Determination of its functional attributions in the host-parasite relationship,
      especially immunopathogenesis of filarial infection, may improve our
      understanding.

PMID- 28453852
TI  - Untangling the Effects of Prior Vaccination on Subsequent Influenza Vaccine
      Effectiveness.

PMID- 28453851
TI  - Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic
      Antimicrobial Peptides.
AB  - Here, we demonstrate that antimicrobial peptides (AMPs) are an effective
      antibiofilm treatment when applied as catheter lock solutions (CLSs) against S.
      aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18,
      Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature
      biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible
      S. aureus isolates from patients with device-related infections grown under in
      vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the
      AMPs against human cells and their immunomodulatory potential in human blood were
      also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP
      during in vitro studies and was also highly effective in eradicating S. aureus
      biofilm infection when used in a CLS rat central venous catheter infection model.
      These data support the potential use of D-Bac8c2,5Leu, alone or in combination
      with other AMPs, in the treatment of S. aureus intravenous catheter infections.

PMID- 28453853
TI  - Single-Molecule Sequencing Revealing the Presence of Distinct JC Polyomavirus
      Populations in Patients With Progressive Multifocal Leukoencephalopathy.
AB  - Background: Progressive multifocal leukoencephalopathy (PML) is a fatal disease
      caused by reactivation of JC polyomavirus (JCPyV) in immunosuppressed individuals
      and lytic infection by neurotropic JCPyV in glial cells. The exact content of
      neurotropic mutations within individual JCPyV strains has not been studied to our
      knowledge. Methods: We exploited the capacity of single-molecule real-time
      sequencing technology to determine the sequence of complete JCPyV genomes in
      single reads. The method was used to precisely characterize individual
      neurotropic JCPyV strains of 3 patients with PML without the bias caused by
      assembly of short sequence reads. Results: In the cerebrospinal fluid sample of a
      73-year-old woman with rapid PML onset, 3 distinct JCPyV populations could be
      identified. All viral populations were characterized by rearrangements within the
      noncoding regulatory region (NCCR) and 1 point mutation, S267L in the VP1 gene,
      suggestive of neurotropic strains. One patient with PML had a single neurotropic
      strain with rearranged NCCR, and 1 patient had a single strain with small NCCR
      alterations. Conclusions: We report here, for the first time, full
      characterization of individual neurotropic JCPyV strains in the cerebrospinal
      fluid of patients with PML. It remains to be established whether PML pathogenesis
      is driven by one or several neurotropic strains in an individual.

PMID- 28453854
TI  - The dynamics of the monomeric restriction endonuclease BcnI during its
      interaction with DNA.
AB  - Endonucleases that generate DNA double strand breaks often employ two independent
      subunits such that the active site from each subunit cuts either DNA strand.
      Restriction enzyme BcnI is a remarkable exception. It binds to the 5?-CC/SGG-3?
      (where S = C or G, '/' designates the cleavage position) target as a monomer
      forming an asymmetric complex, where a single catalytic center approaches the
      scissile phosphodiester bond in one of DNA strands. Bulk kinetic measurements
      have previously shown that the same BcnI molecule cuts both DNA strands at the
      target site without dissociation from the DNA. Here, we analyse the BcnI DNA
      binding and target recognition steps at the single molecule level. We find, using
      FRET, that BcnI adopts either 'open' or 'closed' conformation in solution. Next,
      we directly demonstrate that BcnI slides over long distances on DNA using 1D
      diffusion and show that sliding is accompanied by occasional jumping events,
      where the enzyme leaves the DNA and rebinds immediately at a distant site.
      Furthermore, we quantify the dynamics of the BcnI interactions with cognate and
      non-cognate DNA, and determine the preferred binding orientation of BcnI to the
      target site. These results provide new insights into the intricate dynamics of
      BcnI-DNA interactions.

PMID- 28453856
TI  - Papillon Lefevre syndrome.

PMID- 28453855
TI  - Newly characterized interaction stabilizes DNA structure: oligoethylene glycols
      stabilize G-quadruplexes CH-pi interactions.
AB  - Oligoethylene glycols are used as crowding agents in experiments that aim to
      understand the effects of intracellular environments on DNAs. Moreover, DNAs with
      covalently attached oligoethylene glycols are used as cargo carriers for drug
      delivery systems. To investigate how oligoethylene glycols interact with DNAs, we
      incorporated deoxythymidine modified with oligoethylene glycols of different
      lengths, such as tetraethylene glycol (TEG), into DNAs that form antiparallel G
      quadruplex or hairpin structures such that the modified residues were
      incorporated into loop regions. Thermodynamic analysis showed that because of
      enthalpic differences, the modified G-quadruplexes were stable and the hairpin
      structures were slightly unstable relative to unmodified DNA. The stability of G
      quadruplexes increased with increasing length of the ethylene oxides and the
      number of deoxythymidines modified with ethylene glycols in the G-quadruplex.
      Nuclear magnetic resonance analyses and molecular dynamics calculations suggest
      that TEG interacts with bases in the G-quartet and loop via CH-pi and lone pair
      pi interactions, although it was previously assumed that oligoethylene glycols do
      not directly interact with DNAs. The results suggest that numerous cellular co
      solutes likely affect DNA function through these CH-pi and lone pair-pi
      interactions.

PMID- 28453857
TI  - Fbxl19 recruitment to CpG islands is required for Rnf20-mediated H2B mono
      ubiquitination.
AB  - Histone H2B lysine 120 mono-ubiquitination (H2Bub1) catalyzed by Rnf20 has been
      implicated in normal differentiation of embryonic stem (ES) and adult stem cells.
      However, it remains unknown how Rnf20 is recruited to its specific target
      chromosomal loci for the establishment of H2Bub1. Here, we reveal that Fbxl19, a
      CxxC domain-containing protein, promotes H2Bub1 at the promoters of CpG island
      containing genes by interacting with Rnf20. We show that up-regulation of Fbxl19
      increases the level of global H2Bub1 in mouse ES cells, while down-regulation of
      Fbxl19 reduces the level of H2Bub1. Our genome-wide target mapping unveils the
      preferential occupancy of Fbxl19 on CpG island-containing promoters, and we
      further discover that chromosomal binding of Fbxl19 is required for H2Bub1 of its
      targets. Moreover, we reveal that Fbxl19 is critical for proper differentiation
      of ES cells in collaboration with Rnf20. Altogether, our results demonstrate that
      Fbxl19 recruitment to CpG islands is required for Rnf20-mediated H2B mono
      ubiquitination.

PMID- 28453859
TI  - Temporal and spatial characteristics of highly pathogenic avian influenza
      outbreaks in China during 2004 to 2015.
AB  - Identifying the temporal and spatial characteristics of highly pathogenic avian
      influenza (HPAI) outbreaks is very important for developing effective and
      appropriate countermeasures against HPAI and promoting sustainable development in
      the poultry industry. This study aimed to analyze four aspects of the temporal
      and spatial characteristics of HPAI outbreaks in China, including the frequency
      of HPAI outbreaks, numbers of dead animals (died or culled), types of HPAI
      viruses, and species of infected animals. Temporal characteristics showed that
      the frequency of HPAI outbreaks decreased and then increased, with some years
      deviating from the main trend in 2004 to 2010 and 2011 to 2015, while the largest
      number of dead animals due to HPAI outbreaks was in 2005. During 2004 to 2015,
      HPAI H5N1 was the major type of HPAI virus, and chickens had the greatest risk of
      being infected with HPAI, followed by ducks and geese. The HPAI outbreaks had
      obvious seasonal effects clustered in January to February, June, and November.
      Spatial characteristics revealed that outbreaks were more frequent in Xinjiang,
      Hubei, and Guangdong but caused a larger number of dead animals in Liaoning and
      Shanxi. HPAI H5N1 appeared in 25 provinces, while HPAI H5N2 was mainly localized
      in Hebei and Jiangsu, and HPAI H5N6 occurred in Heilongjiang, Jiangsu, Hunan, and
      Guangdong. HPAI viruses were most frequently detected in chickens and wild birds
      in northern China, while the majority of HPAI infections were identified in
      chickens, ducks, and geese in southern China. Regionally, HPAI outbreaks were
      most frequent in the western region but resulted in larger number of animals
      dying or being culled in the eastern region. These findings could provide a new
      understanding of the distributional characteristics of HPAI outbreaks and offer
      prospects for better prevention and control strategies.

PMID- 28453860
TI  - Different Tales: The Role of Gender in the Oral Narrative-Reading Link Among
      African American Children.
AB  - Evidence suggests that oral narrative skills are a linguistic strength for
      African American children, yet few studies have examined how these skills are
      associated with reading for African American boys and girls. The current study
      uses longitudinal data of a sample of 72 African American 4-year-olds to examine
      how preschool oral narrative skills predict reading from first through sixth
      grades and explores differences by gender. Findings indicate that although girls
      demonstrated stronger narrative skills, their narrative skills did not moderate
      change in reading. For boys, narrative skills moderated change in reading over
      time such that as preschool narrative skills increased, their reading scores
      showed greater change over time. Educational implications and directions for
      future research are discussed.

PMID- 28453858
TI  - Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption
      Syndrome.
AB  - Context: Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital
      defect of the pituitary gland characterized by the triad of a very
      thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary
      gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic
      patterns of inheritance of this disorder are increasingly recognized. Objective:
      The objective of this study was to identify a genetic cause of PSIS in an
      affected child. Methods: Whole exome sequencing (WES) was performed by using
      standard techniques, with prioritized genetic variants confirmed via Sanger
      sequencing. To investigate the effects of one candidate variant on mutant WDR11
      function, Western blotting and coimmunofluorescence were used to assess binding
      capacity, and leptomycin B exposure along with immunofluorescence was used to
      assess nuclear localization. Results: We describe a child who presented in
      infancy with combined pituitary hormone deficiencies and whose brain imaging
      demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin,
      interrupted stalk. WES demonstrated heterozygous missense mutations in two genes
      required for pituitary development, a known loss-of-function mutation in PROKR2
      (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11
      (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11
      loses its capacity to bind to its functional partner, EMX1, and to localize to
      the nucleus. Conclusions: WES in a child with PSIS and his unaffected family
      implicates a digenic mechanism of inheritance. In cases of hypopituitarism in
      which there is incomplete segregation of a monogenic genotype with the phenotype,
      the possibility that a second genetic locus is involved should be considered.

PMID- 28453862
TI  - Prenatal abnormal features of fetal mainstem bronchi: back to the basics.

PMID- 28453861
TI  - Functional lung avoidance and response-adaptive escalation (FLARE) RT:
      Multimodality plan dosimetry of a precision radiation oncology strategy.
AB  - PURPOSE: Nonsmall cell lung cancer (NSCLC) patient radiation therapy (RT) is
      planned without consideration of spatial heterogeneity in lung function or tumor
      response. We assessed the dosimetric and clinical feasibility of functional lung
      avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [99m
      Tc]MAA-SPECT/CT perfused lung while redistributing an escalated boost dose within
      [18 F]FDG-PET/CT-defined biological target volumes (BTV). METHODS: Eight stage
      IIB-IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning
      scans. Perfused lung objectives were derived from scatter/collimator/attenuation
      corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain < 20 Gy
      mean lung dose (MLD). Prescriptions included 60 Gy to the planning target volume
      (PTV) and concomitant boost of 74 Gy mean to biological target volumes (BTV = GTV
      + PET gradient segmentation) scaled to each BTV voxel by relative FDG-PET SUV.
      Dose-painting-by-numbers prescriptions were integrated into commercial treatment
      planning systems via uptake threshold discretization. Dose constraints for lung,
      heart, cord, and esophagus were defined. FLARE RT plans were optimized with
      volumetric modulated arc therapy (VMAT), proton pencil beam scanning (PBS) with
      3%-3 mm robust optimization, and combination of PBS (avoidance) plus VMAT
      (escalation). The high boost dose region was evaluated within a standardized
      SUVpeak structure. FLARE RT plans were compared to reference VMAT plans. Linear
      regression between radiation dose to BTV and normalized FDG PET SUV at every
      voxel was conducted, from which Pearson linear correlation coefficients and
      regression slopes were extracted. Spearman rank correlation coefficients were
      estimated between radiation dose to lung and normalized SPECT uptake. Dosimetric
      differences between treatment modalities were evaluated by Friedman nonparametric
      paired test with multiple sampling correction. RESULTS: No unacceptable
      violations of PTV and normal tissue objectives were observed in 24 FLARE RT
      plans. Compared to reference VMAT plans, FLARE VMAT plans achieved a higher mean
      dose to BTV (73.7 Gy 98195. 61.3 Gy), higher mean dose to SUVpeak (89.7 Gy vs.
      60.8 Gy), and lower mean dose to highly perfused lung (7.3 Gy vs. 14.9 Gy). These
      dosimetric gains came at the expense of higher mean heart dose (9.4 Gy vs. 5.8
      Gy) and higher maximum cord dose (50.1 Gy vs. 44.6 Gy) relative to the reference
      VMAT plans. Between FLARE plans, FLARE VMAT achieved higher dose to the SUVpeak
      ROI than FLARE PBS (89.7 Gy vs. 79.2 Gy, P = 0.01), while FLARE PBS delivered
      lower dose to lung than FLARE VMAT (11.9 Gy vs. 15.6 Gy, P < 0.001). Voxelwise
      linear dose redistribution slope between BTV dose and FDG PET uptake was higher
      in magnitude for FLARE PBS + VMAT (0.36 Gy per %SUVmax ) compared to FLARE VMAT
      (0.27 Gy per %SUVmax ) or FLARE PBS alone (0.17 Gy per %SUVmax ). CONCLUSIONS:
      FLARE RT is clinically feasible with VMAT and PBS. A combination of PBS for
      functional lung avoidance and VMAT for FDG PET dose escalation balanced target
      and normal tissue objective tradeoffs. These results provide a technical platform
      for testing of FLARE RT safety and efficacy within a precision radiation oncology
      trial.

PMID- 28453863
TI  - Use of a geographic information system to assess accessibility to health
      facilities providing emergency obstetric and newborn care in Bangladesh.
AB  - OBJECTIVE: To use a geographic information system (GIS) to determine
      accessibility to health facilities for emergency obstetric and newborn care
      (EmONC) and compare coverage with that stipulated by UN guidelines (5 EmONC
      facilities per 500 000 individuals, >=1 comprehensive). METHODS: A cross
      sectional study was undertaken of all public facilities providing EmONC in 24
      districts of Bangladesh from March to October 2012. Accessibility to each
      facility was assessed by applying GIS to estimate the proportion of catchment
      population (comprehensive 500 000; basic 100 000) able to reach the nearest
      facility within 2 hours and 1 hour of travel time, respectively, by existing road
      networks. RESULTS: The minimum number of public facilities providing
      comprehensive and basic EmONC services (1 and 5 per 500 000 individuals,
      respectively) was reached in 16 and 3 districts, respectively. However, after
      applying GIS, in no district did 100% of the catchment population have access to
      these services. A minimum of 75% and 50% of the population had accessibility to
      comprehensive services in 11 and 5 districts, respectively. For basic services,
      accessibility was much lower. CONCLUSION: Assessing only the number of EmONC
      facilities does not ensure universal coverage; accessibility should be assessed
      when planning health systems.

PMID- 28453864
TI  - Impact on spina bifida screening of shifting prenatal Down syndrome maternal
      serum screening from the second trimester to the first.
AB  - OBJECTIVES: Shifting screening for trisomy 21 to the first trimester has resulted
      in the loss of maternal serum alpha-fetoprotein screening for spina bifida. The
      aim of this study was to study the impact on open spina bifida prenatal
      screening. STUDY DESIGN: We reviewed prenatally diagnosed cases of spina bifida
      over three years: 2009 (only second-trimester screening, MSM2T), 2010 (transient
      period) and 2011 (majority first-trimester screening, MSM1T). Cases were assigned
      to three groups based on maternal serum markers (MSM2T, MSM1T and 'not
      performed'). Gestational age at diagnosis of spina bifida was compared between
      these three groups and between the years 2009 and 2011. RESULTS: Median
      gestational ages at diagnosis of the 742 spina bifida cases between the three
      groups were 22 weeks [18+6 -23], 22+1  weeks [21+3 -23] and 21+4  weeks [14+1 
      23], respectively (P < 0.005). The diagnosis was made at 14-20 weeks in 34.7% for
      MSM2T group versus 8.5% for MSM1T (P < 0.001). Spina bifida diagnosis at 14-20
      weeks declined from 38.8% in 2009 to 13.3% in 2011 (P < 0.001). CONCLUSION: Loss
      of maternal serum alpha-fetoprotein had a tangible effect on the gestational age
      at diagnosis of spina bifida and resulted in a decrease of 25% of cases of spina
      bifida detected before 20 weeks. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28453865
TI  - Saliva and plasma levels of cardiac-related biomarkers in post-myocardial
      infarction patients.
AB  - AIM: To relate cardiac biomarkers, such as cystatin C and growth differentiation
      factor-15 (GDF-15) in saliva to myocardial infarction (MI) and to periodontal
      status, and to investigate the relation between salivary and plasma cardiac
      biomarkers. MATERIALS AND METHODS: Two hundred patients with MI admitted to
      coronary care units and 200 matched controls without MI were included. Dental
      examination and collection of blood and saliva samples was performed 6-10 weeks
      after the MI for patients and in close proximity thereafter for controls.
      Analysing methods: ARCHITECT i4000SR, Immulite 2000 XPi or ELISA. RESULTS: The
      mean age was 62 +/- 8 years and 84% were male. Total probing pocket depth,
      fibrinogen, white blood cell counts and HbA1c were higher in patients than
      controls. GDF-15 levels correlated with most of the included clinical variables
      in both study groups. No correlation was found between plasma and saliva levels
      of cystatin C or GDF-15. CONCLUSION: Salivary cystatin C and GDF-15 could not
      differentiate between MI patients and controls.

PMID- 28453866
TI  - Use of 1-h post-load plasma glucose concentration to identify individuals at high
      risk of developing Type 2 diabetes.

PMID- 28453867
TI  - Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to
      haptens.
AB  - In human dendritic cells (DCs), we previously demonstrated in vitro that syndecan
      1 (SDC1) is downregulated during maturation correlating with enhanced motility.
      We investigated the effects of SDC1 on DC migration in vivo during TNCB(2,4,6
      trinitro-1-chlorobenzene)-induced cutaneous hypersensitivity reaction (CHS) in
      mice. We show that DC in SDC1-deficient mice migrated faster and at a higher rate
      to lymph nodes draining the hapten-painted skin. Adoptive transfer of SDC1
      deficient hapten- and fluorochrome-labelled DC into wild-type (WT) mice led to
      increased and faster migration of DC to paracortical lymph nodes, and to a
      stronger CHS compared to WT DC. In SDC1-/- mice, CCR7 remains longer on the DC
      surface within the first 15-minutes maturation (after LPS-induced maturation). In
      addition, a time-dependent upregulation of CCL2, CCL3, VCAM1 and talin was found
      during maturation in SDC1-/- DC. However, no difference in T-cell-stimulating
      capacity of SDC1-deficient DC was found compared to WT DC. Mechanistically, SDC1
      deficient DC showed enhanced migration towards CCL21 and CCL19. This may result
      from functional overexpression of CCR7 in SDC1-/- DC. Increased and accelerated
      migration of otherwise functionally intact SDC1-deficient DC leads to an
      exacerbated CHS. Based on our results, we conclude that SDC1 on DC negatively
      regulates DC migration.

PMID- 28453868
TI  - Combined aerobic and resistance training decreases inflammation markers in
      healthy men.
AB  - Our primary aim was to study the effects of 24 weeks of combined aerobic and
      resistance training performed on the same day or on different days on
      inflammation markers. Physically active, healthy young men were randomly divided
      into three groups that performed: aerobic and resistance training consecutively
      in the same training session (SS) 2-3 days wk-1 or on alternating days (AD) 4-6
      days wk-1 as well as control (C). The total training volume was matched in the
      training groups. The control group was asked to maintain their habitual physical
      activity and exercise level. Maximal leg press strength (1RM) and peak oxygen
      uptake (VO2peak ) were measured. Abdominal fat mass was estimated with dual
      energy absorptiometry (DXA). High-sensitivity C-reactive protein (hs-CRP),
      interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis
      factor alpha (TNF-alpha), and adipocytokines resistin, adiponectin, and leptin
      were analyzed from plasma samples. Training significantly reduced circulating hs
      CRP, leptin, and resistin in both training groups (P<.05), whereas MCP-1 and TNF
      alpha decreased only in AD (P<.05). Significant correlations were observed
      between changes in abdominal fat mass and corresponding changes in MCP-1, leptin,
      adiponectin, and resistin. Long-term combined aerobic and resistance training
      reduced markers of subclinical inflammation in healthy young men. The results
      indicate that a higher frequency of individual exercise sessions might be more
      beneficial with respect to the anti-inflammatory effects of physical activity.
      The decreases in inflammation markers seem to be related to decreases in
      abdominal fat mass.

PMID- 28453869
TI  - Non-surgical treatment of peri-implant mucositis and peri-implantitis at two
      piece zirconium implants: A clinical follow-up observation after up to 3 years.
AB  - OBJECTIVES: To assess the long-term clinical outcomes following non-surgical
      therapy of peri-implant diseases at two-piece zirconium implants. MATERIAL AND
      METHODS: A total of 27 patients suffering from either (i) peri-implant mucositis
      (n = 24 implants), or (ii) peri-implantitis (n = 16 implants) completed a mean
      follow-up period of 32.8 +/- 2.85 months (median: 34 months). The initial
      treatment procedures included (i) mechanical debridement + local antiseptic
      therapy using chlorhexidine digluconate (MD + CXH), or (ii) Er:YAG laser
      monotherapy (ERL). The primary outcome was disease resolution (i.e. absence of
      bleeding on probing (BOP) at mucositis sites/absence of BOP and probing pocket
      depths (PD) >=6 mm at peri-implantitis sites). RESULTS: Resolution of peri
      implant mucositis and peri-implantitis was obtained in 7/14 (50.0%; p = .003) and
      5/13 (38.5%; p = .001) of the patients investigated. This corresponded to 54.2%
      (13/24) and 50.0% (8/16) at the implant level respectively. CONCLUSION: Both MD +
      CHX and ERL were effective on the long-term, but failed to achieve a complete
      disease resolution.

PMID- 28453870
TI  - Clinically relevant discordances identified after tertiary reassessment of
      fetuses with isolated congenital diaphragmatic hernia.
AB  - OBJECTIVE: Fetoscopic endoluminal tracheal occlusion (FETO) may improve outcome
      of severe isolated congenital diaphragmatic hernia (iCDH). We aimed to identify
      any discrepancy between initial assessment at the referring hospital and the
      evaluation at the fetal surgery center, and to document parental decisions
      following counseling for fetal surgery. DESIGN: Single center retrospective study
      on patients with presumed iCDH either referred for assessment and counseling or
      referred for fetal surgery. Discordant findings were defined as either a >10%
      difference in lung size, discordant liver position or associated anomalies.
      RESULTS: Outcomes from 129 consecutive assessments over 24 months were analyzed.
      Among fetal surgery referrals, 2% did not have CDH, and 10% had undiagnosed
      associated anomalies. Liver position was discordant in 7%. Thirty-three per cent
      had discordant lung size. Ninety-four per cent of patients eligible for surgery
      underwent FETO. In patients referred because of suspicion of CDH, associated
      anomalies were found in 14%. Fetal liver and lung assessments were discordant in
      50% resp. 38%. Of those patients eligible for FETO, 26% requested termination.
      For three patients, the postnatal course was marked by a genetic or syndromic
      additional diagnosis. CONCLUSION: Discordances between initial assessment before
      referral and evaluation in our institution were frequent, some of them clinically
      relevant. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28453872
TI  - Cross-sectional study of the feasibility of urinating in a standing position
      among women in the third trimester of pregnancy.

PMID- 28453871
TI  - Elevated cerebrospinal fluid tumour necrosis factor is associated with acute and
      long-term neurocognitive impairment in cerebral malaria.
AB  - Systemic tumour necrosis factor-alpha (TNF-alpha) may contribute to the
      pathogenesis of cerebral malaria (CM) by promoting endothelial activation and
      parasite sequestration. However, less is known about the role of central nervous
      system (CNS) TNF-alpha in CM. We assessed plasma (n=249) and cerebrospinal fluid
      (CSF) (n=167) TNF-alpha levels in Ugandan children with CM, plasma TNF-alpha in
      Ugandan community control children (n=198) and CSF TNF-alpha in North American
      control children who had recovered from leukaemia (n=13). Plasma and CSF TNF
      alpha were measured by magnetic bead assay. We compared plasma and CSF TNF-alpha
      levels in children with CM to mortality, acute and chronic neurologic deficits
      and long-term neurocognitive impairment. Plasma and CSF TNF-alpha levels were
      higher in CM than control children (P<.0001 for both). CSF TNF-alpha levels were
      higher in children who had neurologic deficits at discharge or 6-month follow-up
      (P<=.05 for both). Elevated CSF but not plasma TNF-alpha was associated with
      longer coma duration (Spearman's rho .18, P=.02) and deficits in overall
      cognition in children 5 years and older (beta coefficient -.74, 95% CI -1.35 to 
      0.13, P=.02). The study findings suggest that CNS TNF-alpha may be involved in
      the development of acute and chronic neurologic and cognitive sequelae in
      children with CM.

PMID- 28453873
TI  - Induced-orientation of nitrogen monoxide and azide ion vibrations in human
      hemoglobin in bidistilled water solution under a static magnetic field.
AB  - In this study, we report the effects of static magnetic fields (SMFs) at 200 mT
      on different hemoglobin aqueous solutions, in the absence and in the presence of
      sucrose and trehalose, studied by FTIR spectroscopic techniques. Significant
      decrease in intensity of Amide I and Amide II vibration bands was observed after
      6 h exposure for hemoglobin in bidistilled water solution. Also, it was observed
      that the decrease in intensity of the Amide I band was larger than the Amide II
      after exposure. This result can be explained assuming that an SMF induces
      increase of hydrogen bonding in hemoglobin in bidistilled water solution. In
      particular, the use of second-derivative analysis highlighted two absorption
      peaks at 1907 and 2022 cm-1 that can be attributed to nitrogen monoxide vibration
      and antisymmetric stretch of azide ion bound, respectively. These vibrations
      increased significantly after exposure to the SMF (P < 0.01). This result can be
      explained assuming that exposure to an SMF induces the orientation of nitrogen
      monoxide and azide ion ligands toward the direction of the field. Finally, it was
      observed that the addition of sucrose and trehalose in hemoglobin aqueous
      solution inhibited such alterations, suggesting that bioprotective effectiveness
      of these disaccharides occurs after exposure to an SMF. Bioelectromagnetics.
      38:447-455, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 28453874
TI  - Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene
      and increased risk for myocardial infarction in patients with premature coronary
      artery disease.
AB  - BACKGROUND: A number of matrix metalloproteinase (MMP) gene polymorphisms has
      been identified which may be probably related to premature myocardial infarction
      (MI). OBJECTIVE: We assessed the relationship between the two polymorphisms of
      the MMP9 gene including R279Q and C1562T and occurrence of premature MI. METHODS:
      The study has two phases including a case-control study as the first phase and
      cohort study as the second phase. Initially, 1000 patients with premature
      coronary artery disease were classified into MI and non-MI groups. Genotyping of
      the polymorphism was conducted by PCRRFLP and high-resolution melting techniques.
      Given the two conditions of patients residing in Tehran and faced with their
      first episode of MI, 640 of 1000 study samples previously followed up with a
      median follow-up time of 45.74 months were assessed in a retrospective cohort
      phase regarding long-term major adverse cardiac events (MACE). RESULTS: The
      prevalence of wild, heterozygous, and mutant genotypes of R279Q polymorphism in
      MI group was 14.5%, 57.3%, and 28.2% and in non-MI group was 36.9%, 38.4%, and
      24.7%, respectively, with a considerable difference (P<.001). There was a
      significant difference in the prevalence of wild, heterozygous, and mutant
      genotypes of C1562T polymorphisms in MI group (12.4%, 41.2%, and 46.4%,
      respectively) and in non-MI group (46.8%, 38.6%, and 14.7%, respectively;
      P<.001). No difference was found in total MACE-free survival rate between
      genotypes of R279Q and C1562T polymorphisms. CONCLUSION: C1562T and R279Q
      polymorphisms are associated with the susceptibility to premature MI, but cannot
      predict long-term cardiac events in these patients.

PMID- 28453875
TI  - Depression symptoms are persistent in Type 2 diabetes: risk factors and outcomes
      of 5-year depression trajectories using latent class growth analysis.
AB  - AIMS: To describe the long-term trajectories of depression symptom severity in
      people with Type 2 diabetes, and to identify predictors and associates of these
      trajectories. METHODS: A community-dwelling cohort of 1201 individuals with Type
      2 diabetes from the Fremantle Diabetes Study Phase II was followed for 5 years.
      The nine-item version of the Patient Health Questionnaire was administered
      annually to assess depression symptoms, and biomedical and psychosocial measures
      were assessed at baseline and biennially. Latent class growth analysis was used
      to identify classes of depression severity trajectories and associated outcomes,
      and logistic regression models were used to determine predictors of class
      membership. RESULTS: Three trajectories of depression symptoms were identified:
      continuously low depression symptoms (85.2%); gradually worsening symptoms that
      then began to improve (persistent depression - low-start; 7.3%); and gradually
      improving symptoms which later worsened (persistent depression - high-start;
      7.5%). Younger age, being a woman, and a lifetime history of major depressive
      disorder, were associated with greater risk of persistent depression symptoms.
      Persistent depression was associated with consistently higher BMI over time, but
      not with changes in HbA1c or self-monitoring of blood glucose. CONCLUSIONS: A
      subset of individuals with Type 2 diabetes is at risk of depression symptoms that
      remain elevated over time. Younger, overweight individuals with a history of
      depression may benefit from early and intensive depression management and ongoing
      follow-up as part of routine Type 2 diabetes care.

PMID- 28453876
TI  - Age-associated changes in the blood-brain barrier: comparative studies in human
      and mouse.
AB  - AIMS: While vascular pathology is a common feature of a range of
      neurodegenerative diseases, we hypothesized that vascular changes occur in
      association with normal ageing. Therefore, we aimed to characterize age
      associated changes in the blood-brain barrier (BBB) in human and mouse cohorts.
      METHODS: Immunohistochemistry and Evans blue assays were used to characterize BBB
      dysfunction (tight junction protein expression and serum plasma protein
      accumulation), vascular pathology (pericyte loss and vascular density) and glial
      pathology (astrocyte and microglial density) in ageing neurological control human
      prefrontal cortex (a total of 23 cases from 5 age groups representing the
      spectrum of young adult to old age: 20-30 years, 31-45 years, 46-60 years, 61-75
      years and 75+) and C57BL/6 mice (3 months, 12 months, 18 months and 24 months, n
      = 5/6 per group). RESULTS: Quantification of the tight junction protein ZO-1
      within the cortex and cerebellum of the mouse cohort showed a significant trend
      to both increased number (cortex P < 0.001, cerebellum P < 0.001) and length
      (cortex P < 0.001, cerebellum P < 0.001) of junctional breaks associated with
      increasing age. GFAP expression significantly correlated with ageing in the mice
      (P = 0.037). In the human cohort, assessment of human protein accumulation
      (albumin, fibrinogen and human IgG) demonstrated cells morphologically resembling
      clasmatodendritic astrocytes, indicative of BBB dysfunction. Semiquantitative
      assessment of astrogliosis in the cortex expression revealed an association with
      age (P = 0.003), while no age-associated changes in microglial pathology,
      microvascular density or pericyte coverage were detected. CONCLUSIONS: This study
      demonstrates BBB dysfunction in normal brain ageing, both in human and mouse
      cohorts.

PMID- 28453877
TI  - Asymmetric changes in circulating insulin levels after an increase compared with
      a reduction in insulin pump basal rate in people with Type 1 diabetes.
AB  - AIMS: To investigate circulating insulin profiles after a clinically relevant
      insulin pump basal rate increase vs a reduction, and the associated glucose
      responses. METHODS: A cohort of 12 adults with Type 1 diabetes undertook this two
      stage university hospital study using Accu-Chek pumps (Roche Diagnostics,
      Mannheim, Germany) and insulin aspart. An insulin basal rate change of 0.2 unit/h
      (increase in first stage, reduction in second stage) was implemented at ~09:30 h,
      after a single overnight basal rate (without bolus insulin), while fasting
      participants rested. Frequent venous samples for the assessment of plasma free
      insulin, glucose and cortisol were collected from 60 min before until 300 min
      after rate change. The primary outcome was time to steady-state insulin. RESULTS:
      The 0.2-unit/h rate change represented a mean +/- sd alteration of 23 +/- 6%.
      After the rate increase, the median (interquartile range) times to 80% and 90%
      steady-state insulin were 170 (45) min and 197 (87) min, respectively. By
      contrast, after rate reduction, 80% steady-state insulin was not achieved. After
      the rate increase, mean +/- se insulin levels increased by 4.3 +/- 3.1%, 12.0 +/-
      2.9% and 25.6 +/- 2.6% at 60, 120 and 300 min, respectively (with no significant
      difference until 180 min). After the rate reduction, insulin decreased by 8.3 +/-
      3.0% at 300 min (with no significant difference until 300 min). After rate
      reduction, glucose levels paradoxically declined by 17.4 +/- 3.7% after 300 min;
      cortisol levels also fell during observation (P = 0.0003). CONCLUSIONS: The time
      to circulating insulin change after a 0.2-unit/h basal rate change was
      substantial, and was greater after a reduction than after an increase. Counter
      regulatory hormone circadian variation may affect glycaemia when implementing
      minor changes at low basal rates. Both direction of basal rate change, and time
      of day, warrant consideration when anticipating the clinical effects of basal
      rate changes.

PMID- 28453879
TI  - Computers in mass spectrometry.

PMID- 28453878
TI  - Titanium implant functionalization with phosphate-containing polymers may favour
      in vivo osseointegration.
AB  - AIM: Osseointegration of titanium implants is predictable, but can be improved
      via surface functionalization. MATERIALS AND METHODS: One hundred and twenty
      implants were installed in parietal bone of 12 domestic pigs and left to heal for
      1 or 3 months. Five groups were defined according surface treatments: immersion
      in water (H2 O), 10% polyphosphoric acid (PPA10), 1% phosphorylated pullulan
      (PPL1), 10% phosphorylated pullulan (PPL10) or 10% phosphorylated pullulan + 1
      MUg bone morphogenetic protein-2 (PPL10 BMP). As primary outcome, implant
      osseointegration was evaluated by quantitative histology, namely peri-implant
      bone formation (B/T in %) and bone-to-implant contact (BIC in %) for each healing
      period. The Wilcoxon signed-rank test and Mann-Whitney U-test with alpha = 0.05
      were performed. RESULTS: PPL10 and PPA10 groups showed significantly higher B/T
      and BIC results than the control (H2 O) group at 1-month (p < .05). No
      significant difference was found between PPL1 and H2 O or between PPL10 BMP and
      H2 O, irrespective of healing time (1 or 3 months) or investigated parameter (B/T
      and BIC; p > .05). After 3 months, no experimental group showed a significant
      difference compared to the control group (H2 O) for both investigated parameters
      (B/T and BIC; p > .05). CONCLUSION: Functionalizing titanium implants with
      inorganic or organic phosphate-containing polymers at 10 wt% concentration may
      stimulate peri-implant bone formation and implant osseointegration at early
      healing times.

PMID- 28453880
TI  - Predicting postnatal renal function of prenatally detected posterior urethral
      valves using fetal diffusion-weighted magnetic resonance imaging with apparent
      diffusion coefficient determination.
AB  - OBJECTIVE: The objective of this study was to evaluate the accuracy of fetal
      diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient
      (ADC) determination to predict postnatal renal function (nadir creatinine at 1
      year and eGFR) of men with posterior urethral valves (PUV). METHODS: Between 2003
      and 2014, 11 MRI were performed on fetuses (between 28 and 32 weeks) in whom
      second trimester sonography suggested severe bilateral urinary tract anomalies,
      suspected of PUV. RESULTS: The ADC of the 11 fetuses ranged from 1.3 to 2.86 mm2 
      s-1 (median = 1.79 mm2  s-1 , normal range for fetal kidney: 1.1-1.8). Two
      pregnancies with ADC > 2.6 mm2  s-1 were interrupted; the autopsy confirmed PUV
      and Potter syndrome. For the remaining nine babies, the follow-up was 5.4 years
      (0.8-10). Four children with abnormal ADC (1.8-2.3) had chronic kidney disease.
      The remaining five cases with normal nadir creatinine and eGFR had normal ADC.
      One case with unilateral elevated ADC had a poor ipsilateral renal function on
      dimercaptosuccinic acid scan. CONCLUSION: Here, it seems that diffusion-weighted
      magnetic resonance imaging with ADC determination could be useful in accurately
      evaluating fetal kidneys in PUV and predicting renal function. It may be an
      additional, non-invasive method when biologic and sonographic findings are
      inconclusive, especially in the case of oligohydramnios. Further studies are
      needed to confirm our data. (c) 2017 John Wiley & Sons, Ltd.

PMID- 28453881
TI  - Effect of an acute exercise bout on immediate post-exercise irisin concentration
      in adults: A meta-analysis.
AB  - Irisin is a recently discovered myokine that increases adipocyte metabolism,
      induces further "browning" of white adipose tissue, and enhances glucose
      metabolism. No study has ever determined how an acute bout of exercise impacts
      immediate post-exercise irisin concentration using a meta-analytic approach. The
      purpose of this study is to determine the impact of an acute bout of exercise on
      the magnitude of post-exercise irisin concentration in adults using meta-analytic
      procedures. Searches were performed on PubMed, EMBASE, CINAHL, PEDro, SCOPUS, and
      SPORTDiscus databases. Effect summaries were obtained using random-effects
      models. Random-effects single and multiple meta-regressions were performed to
      determine relationships between, and potential confounding effects of, variables
      of interest. Ten articles were retained for the final meta-analysis, producing 21
      study estimates. An acute bout of exercise was accompanied by a post-exercise
      average increase in irisin concentration of 15.0 (95% CI: 10.8%-19.3%). There was
      no significant relationship between post-exercise irisin concentration and age,
      intensity of aerobic exercise, or type of exercise training session (resistance
      vs aerobic training). Fitness level and body mass index were identified as
      significant predictive variables for post-exercise irisin concentration. However,
      a multiple meta-regression model identified fitness level as the single best
      predictor, with being fit (21.1%+/-2.2%) associated with a nearly twofold
      increase in post-exercise irisin concentration, compared with being unfit
      (11.8%+/-2.1%). Immediately following an acute bout of exercise, irisin
      concentration increases substantially in adults, with fitness level as an
      important modifier for the effect.

PMID- 28453882
TI  - The validity of the observed-to-expected lung-to-head ratio in congenital
      diaphragmatic hernia in an era of standardized neonatal treatment; a multicenter
      study.
AB  - OBJECTIVE: To assess the predictive value of observed-to-expected lung-to-head
      ratio (O/E LHR) for survival and chronic lung disease (CLD) in survivors of left
      sided congenital diaphragmatic hernia (CDH) in an era of standardized neonatal
      treatment, and to evaluate the predictive value of the O/E LHR trajectory for
      survival. METHODS: This retrospective cohort study was performed in two high
      volume CDH centers in the Netherlands in prenatally detected, isolated left-sided
      CDH patients born between 2008 and 2014. O/E LHR and liver position were
      determined using 2D-ultrasonography at three time points during gestation from 19
      weeks onwards. Ultrasound measurements were performed on stored ultrasound data
      by one single experienced operator blinded to postnatal outcome. RESULTS: Of the
      122 included cases, 77.9% survived of whom 38.9% developed CLD. A significant
      association was found between the first measured O/E LHR and survival and
      development of CLD in survivors. Prenatal liver position did not have additional
      predictive value. No significant association was found between the trajectory of
      the O/E LHR and survival. CONCLUSION: In an era of standardized neonatal
      treatment for neonates with CDH, the first measured O/E LHR per patient
      significantly predicts survival and development of CLD in survivors in isolated
      left-sided CDH infants. (c) 2017 The Authors. Prenatal Diagnosis published by
      John Wiley & Sons, Ltd.

PMID- 28453883
TI  - Stomatal function, density and pattern, and CO2 assimilation in Arabidopsis
      thaliana tmm1 and sdd1-1 mutants.
AB  - Stomata modulate the exchange of water and CO2 between plant and atmosphere.
      Although stomatal density is known to affect CO2 diffusion into the leaf and thus
      photosynthetic rate, the effect of stomatal density and patterning on CO2
      assimilation is not fully understood. We used wild types Col-0 and C24 and
      stomatal mutants sdd1-1 and tmm1 of Arabidopsis thaliana, differing in stomatal
      density and pattern, to study the effects of these variations on both stomatal
      and mesophyll conductance and CO2 assimilation rate. Anatomical parameters of
      stomata, leaf temperature and carbon isotope discrimination were also assessed.
      Our results indicate that increased stomatal density enhanced stomatal
      conductance in sdd1-1 plants, with no effect on photosynthesis, due to both
      unchanged photosynthetic capacity and decreased mesophyll conductance. Clustering
      (abnormal patterning formed by clusters of two or more stomata) and a highly
      unequal distribution of stomata between the adaxial and abaxial leaf sides in
      tmm1 mutants also had no effect on photosynthesis. Except at very high stomatal
      densities, stomatal conductance and water loss were proportional to stomatal
      density. Stomatal formation in clusters reduced stomatal dynamics and their
      operational range as well as the efficiency of CO2 transport.

PMID- 28453884
TI  - Shout in fury but smile at life: A portrait of an adolescent with cancer on the
      Youth Project in Milan.

PMID- 28453885
TI  - Lineage switch under blinatumomab treatment of relapsed common acute
      lymphoblastic leukemia without MLL rearrangement.
AB  - Blinatumomab is a bispecific T-cell engaging alphaCD19 antibody used in
      refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL).
      Recently, lineage switch to a myeloid phenotype has been described following CD19
      targeting treatment in three pediatric patients with mixed lineage leukemia (MLL)
      rearranged ALL. We report the case of a female who received blinatumomab for a
      first relapse of ALL without MLL alterations. She suffered from a second relapse
      early after hematopoietic stem cell transplantation and was treated with
      blinatumomab again. During this treatment, the leukemia lost CD19 expression as
      well as nearly all other B-cell markers, while still harboring the initial
      minimal residual disease marker, and switched to a myeloid phenotype.

PMID- 28453886
TI  - Remote diagnosis of traumatic dental injuries using digital photographs captured
      via a mobile phone.
AB  - BACKGROUND: Intra-oral photographs have been aided diagnosis of several
      pathologies in teledentistry. Mobile phone cameras may produce high-quality
      photographs, presenting itself as a viable tool for remote diagnosis of traumatic
      dental injuries. AIM: To evaluate the levels of interexaminer agreement in cases
      of traumatic dental injuries when comparing diagnoses conducted in person and
      remotely. MATERIAL AND METHODS: The sample included 40 patients with 73
      traumatized teeth, and a total of 90 diagnoses, who had presented to two dental
      clinics, one private, and the other public, in Brazil's Federal District. The
      dental history and clinical examination data were registered in electronic forms,
      and digital photographs were captured with a mobile phone camera and uploaded to
      a cloud drive. Six remote examiners formulated their diagnoses based solely on
      photographic analysis. Thereafter, they were provided with additional clinical
      data and asked to provide a second round of diagnoses. These diagnoses were
      compared to those conducted in person, which were considered the gold standard.
      The data were analyzed with Gwet's AC1 interexaminers' measure to evaluate the
      agreement between the in-surgery and remote diagnoses. RESULTS: The levels of
      interexaminer agreement between the in-surgery and remote diagnoses formulated
      exclusively with images were 0.83 or higher (95% confidence interval: 0.73-0.91),
      and 0.93 or higher (95% confidence interval: 0.88-0.97), when clinical
      information was available. CONCLUSION: The precision of the remote diagnoses was
      comparable to the diagnoses conducted in person. The levels of interexaminer
      agreement were higher when clinical data were included with the images. Mobile
      phones may be an effective tool for capturing images that assist in the remote
      diagnosis of traumatic dental injuries.

PMID- 28453887
TI  - Self-management strategies used by head and neck cancer survivors following
      completion of primary treatment: A directed content analysis.
AB  - OBJECTIVE: Head and neck cancer (HNC) survivors encounter unique challenges
      following treatment. This study aimed to identify self-management strategies that
      HNC survivors use to overcome these posttreatment challenges. METHODS: Twenty
      seven individuals from 4 designated cancer centres in Ireland were interviewed
      about self-management strategies that helped them overcome challenges following
      HNC treatment. Interviews were audio-recorded, transcribed, and analysed using
      directed content analysis. RESULTS: Twenty self-management strategy types
      (encompassing 77 specific strategies) were identified. The most frequently used
      self-management strategy types were self-sustaining (used by 26 survivors), self
      motivating (n = 25), and proactive problem solving (n = 25). The most frequently
      used specific strategies were adaptive approaches to ongoing physical
      consequences of HNC and its treatment (n = 24), customising dietary practices (n
      = 24), and maintaining a positive outlook (n = 22). CONCLUSIONS: The study
      identified strategies that helped HNC survivors to self-manage posttreatment
      challenges. This information could inform the design/development of self
      management interventions tailored towards HNC survivors.

PMID- 28453888
TI  - Live imaging of extracellular signal-regulated kinase and protein kinase A
      activities during thrombus formation in mice expressing biosensors based on
      Forster resonance energy transfer.
AB  - : Essentials Spatiotemporal regulation of protein kinases during thrombus
      formation remains elusive in vivo. Activities of protein kinases were live imaged
      in mouse platelets at laser-ablated arterioles. Protein kinase A was activated in
      the dislodging platelets at the downstream side of the thrombus. Extracellular
      signal-regulated kinase was activated at the core of contracting platelet
      aggregates. SUMMARY: Background The dynamic features of thrombus formation have
      been visualized by conventional video widefield microscopy or confocal microscopy
      in live mice. However, owing to technical limitations, the precise spatiotemporal
      regulation of intracellular signaling molecule activities, which have been
      extensively studied in vitro, remains elusive in vivo. Objectives To visualize,
      by the use of two-photon excitation microscopy of transgenic mice expressing
      Forster resonance energy transfer (FRET) biosensors for extracellular signal
      regulated kinase (ERK) and protein kinase A (PKA), ERK and PKA activities during
      thrombus formation in laser-injured subcutaneous arterioles. Results When a core
      of densely packed platelets had developed, ERK activity was increased from the
      basal region close to the injured arterioles. PKA was activated at the downstream
      side of an unstable shell overlaying the core of platelets. Intravenous
      administration of a MEK inhibitor, PD0325901, suppressed platelet tethering and
      dislodged platelet aggregates, indicating that ERK activity is indispensable for
      both initiation and maintenance of the thrombus. A cAMP analog, dbcAMP, inhibited
      platelet tethering but failed to dislodge the preformed platelet aggregates,
      suggesting that PKA can antagonize thrombus formation only in the early phase.
      Conclusion In vivo imaging of transgenic mice expressing FRET biosensors will
      open a new opportunity to visualize the spatiotemporal changes in signaling
      molecule activities not only during thrombus formation but also in other
      hematologic disorders.

PMID- 28453891
TI  - Toward a better risk stratification for late antibody-mediated rejection in ABO
      incompatible kidney recipients.

PMID- 28453889
TI  - Discrepant platelet and plasma von Willebrand factor in von Willebrand disease
      patients with p.Pro2808Leufs*24.
AB  - : Essentials von Willebrand factor (VWF) is synthesized in endothelial cells and
      platelet precursors. Type 3 patients with Pro2808Leufs*24 have lower bleeding
      scores than other type 3s. The Pro2808Leufs*24 variant was examined in patient
      platelets and endothelial cells. Type 3s with this variant contain releaseable
      VWF, possibly reducing bleeding. SUMMARY: Background A novel variant,
      p.Pro2808Leufs*24, in the von Willebrand factor (VWF) gene was previously
      identified in the Canadian von Willebrand disease (VWD) patient population.
      Clinical observations of type 3 VWD patients with this variant indicate a milder
      bleeding phenotype compared with other type 3 patients. Objective To assess the
      effect of the Pro2808Leufs*24 variant on the molecular pathogenesis of VWD and
      correlate this with the phenotype observed in patients. Patients/Methods
      Phenotypic data from individuals in the Canadian type 3 VWD study were analyzed.
      VWF expression in platelets and plasma was assessed via immunoblotting. Cellular
      expression of VWF in platelets and blood outgrowth endothelial cells (BOEC) was
      examined via immunofluorescence microscopy and biochemical analysis in a type 3
      index case and family member with Pro2808Leufs*24. Results Twenty-six individuals
      with the Pro2808Leufs*24 variant (16 type 3 VWD homozygous or compound
      heterozygous and 10 heterozygous family members) were studied. Bleeding scores
      were lower in type 3 patients with Pro2808Leufs*24 compared with type 3 patients
      with other variants, confirming a milder bleeding phenotype. Immunoblotting of
      platelet lysates detected VWF in the platelets of type 3 patients with
      Pro2808Leufs*24. Examination of an index case detected VWF within platelets via
      immunofluorescence microscopy, and in vitro experiments showed that this VWF was
      released upon platelet activation. Patient BOECs showed decreased VWF synthesis
      and secretion, although some VWF-containing granules were observed. Conclusion
      Type 3 VWD patients with the Pro2808Leufs*24 have bioavailable platelet-derived
      VWF that may produce a milder bleeding phenotype than other type 3s.

PMID- 28453890
TI  - Less is more: Patient-level meta-analysis reveals paradoxical dose-response
      effects of a computer-based social anxiety intervention targeting attentional
      bias.
AB  - BACKGROUND: The past decade of research has seen considerable interest in
      computer-based approaches designed to directly target cognitive mechanisms of
      anxiety, such as attention bias modification (ABM). METHODS: By pooling patient
      level datasets from randomized controlled trials of ABM that utilized a dot-probe
      training procedure, we assessed the impact of training "dose" on relevant
      outcomes among a pooled sample of 693 socially anxious adults. RESULTS: A
      paradoxical effect of the number of training trials administered was observed for
      both posttraining social anxiety symptoms and behavioral attentional bias (AB)
      toward threat (the target mechanism of ABM). Studies administering a large
      (>1,280) number of training trials showed no benefit of ABM over control
      conditions, while those administering fewer training trials showed significant
      benefit for ABM in reducing social anxiety (P = .02). These moderating effects of
      dose were not better explained by other examined variables and previously
      identified moderators, including patient age, training setting (laboratory vs.
      home), or type of anxiety assessment (clinician vs. self-report). CONCLUSIONS:
      Findings inform the optimal dosing for future dot-probe style ABM applications in
      both research and clinical settings, and suggest several novel avenues for
      further research.

PMID- 28453892
TI  - The psychosocial impact of contralateral risk reducing mastectomy (CRRM) on
      women: A rapid review.
AB  - OBJECTIVES: For women who have been diagnosed with unilateral breast cancer,
      there is an increasing trend for them to request removal of the contralateral
      healthy breast, the so-called contralateral risk reducing mastectomy (CRRM). The
      current literature is only just beginning to identify patient-reported reasons
      for undergoing CRRM and associated patient-reported outcomes. It is also unclear
      whether women at moderate/high risk of developing a subsequent primary
      contralateral breast cancer report similar outcomes to those considered to be at
      low/average risk. This lack of knowledge provides the rationale for this review.
      METHODS: A rapid review methodology was undertaken to identify and explore the
      published research literature focused on the longer term (>5 y) psychosocial
      impacts on women who undergo CRRM. RESULTS: Fifteen studies were identified. No
      UK studies were identified. High satisfaction and psychosocial well-being were
      consistently reported across all studies. Reducing the risk of a subsequent
      contralateral breast cancer and therefore reducing cancer-related anxiety, and
      satisfaction with cosmesis, were key themes running across all studies explaining
      satisfaction. Dissatisfaction was associated with adverse effects such as poor
      cosmesis, body image changes, femininity, sexual relationships, reoperations for
      acute and longer term complications, and reconstructive problems. CONCLUSIONS:
      Satisfaction and psychological well-being following CRRM was consistently high
      across all studies. However, the findings suggest women need to be more fully
      informed of the risks and benefits of CRRM and/or immediate/delayed
      reconstruction to support informed decision making.

PMID- 28453893
TI  - Who are the support persons of haematological cancer survivors and how is their
      performance perceived?
AB  - OBJECTIVE: To explore: (1) how haematological cancer survivors and their support
      persons perceive the overall performance of the support person; (2) disagreement
      between survivor and support person ratings; and (3) characteristics associated
      with support persons rating their performance poorly. METHODS: This is a substudy
      of a larger project of Australian haematological cancer survivors and their
      support persons. For this substudy, haematological cancer survivors were
      recruited from 4 Australian population-based cancer registries and asked to pass
      on a questionnaire package to their support persons. Survivors who passed on a
      questionnaire package to their support person were asked to answer questions
      about the support person and how they perceived the support person's performance.
      Similarly, support persons answered questions on their own performance as a
      support person. RESULTS: A total of 924 haematological cancer survivors and 821
      support persons were eligible for this study. Most survivors rated their support
      person as performing very well (84%) while less than half (48%) of support
      persons rated their own performance as very well. There was significant
      disagreement between survivor and their support person (dyad) ratings of the
      support person's performance. Support persons with above normal levels of
      depression (vs those with normal levels) had significantly higher odds of rating
      their own performance as "not well/somewhat well." CONCLUSIONS: Health care
      providers should consider providing additional education and skills-based
      interventions to support persons who experience increased symptoms of depression.

PMID- 28453894
TI  - Efficacy and safety of oral propranolol for infantile hemangioma in Japan.
AB  - BACKGROUND: There have been few reports on the efficacy and safety of oral
      propranolol at 3 mg/kg/day for infantile hemangioma (IH) in Japanese patients.
      METHODS: A multicenter, open-label phase III study was conducted to evaluate the
      efficacy and safety of oral propranolol solution in Japanese infants aged 35-150
      days with proliferating IH. Thirty-two patients were enrolled in the study,
      received propranolol solution for 24 weeks at 3 mg/kg/day, and completed the
      study. RESULTS: The success rate (complete or nearly complete resolution) at week
      24 (primary endpoint) was 78% (95%CI: 60-91%). The improvement rate since the
      previous visit was 100% (32/32) after week 5. Overall, the IH surface area,
      maximum diameter, and color intensity all decreased over time. Consistency in
      assessment between the centralized and the investigator on-site assessments was
      observed in 26 patients. Of the 32 patients, 11 needed further treatment other
      than the study drug. The incidence of adverse events (AE) and drug-related AE was
      97% and 31%, respectively. AE that occurred in >=two patients were either typical
      of propranolol use (such as blood pressure decrease) or common events in infants.
      AE that resulted in dose reduction were observed in two patients, but no serious
      AE or AE that led to study drug discontinuation were observed. CONCLUSION: Oral
      propranolol solution at 3 mg/kg/day is effective and safe in Japanese IH
      patients.

PMID- 28453895
TI  - A 1,2-Addition Pathway for C(sp2 )-H Activation at a Dinickel Imide.
AB  - A dinickel imido complex was synthesized using a redox-active naphthyridine
      diimine supporting ligand. Upon coordination of an external ligand, the Ni2 core
      was disrupted, triggering an aromatic C-H activation reaction to generate a Ni2
      (MU-NHAr)(Ar) species. This intermediate is capable of liberating free carbazole
      and phenanthridine products upon heating or treatment with excess tBuNC.
      Collectively, these studies establish a kinetically facile 1,2-addition mechanism
      for C(sp2 )-H activation, taking advantage of cooperative reactivity between two
      Ni centers.

PMID- 28453897
TI  - Clinical outcome of childhood chronic immune thrombocytopenia: A 38-year
      experience from a single tertiary center in Thailand.
AB  - BACKGROUND: There is limited information on long-term follow-up and prognostic
      factors for remission among children diagnosed with chronic immune
      thrombocytopenia (ITP). The aim of this study was to determine clinical outcomes
      and factors influencing remission in childhood chronic ITP. STUDY DESIGN: The
      hospital records of children aged 0-15 years diagnosed with chronic ITP were
      retrospectively reviewed. Kaplan-Meier curves were fit to estimate the median
      time to complete remission with 95% confidence intervals (CIs). Multivariate Cox
      proportional hazards regression models were used to identify independent factors
      for remission. RESULTS: A total of 113 patients were included in the analysis.
      The number of children achieving complete remission was 49 (46%) and the median
      time to remission was 7.1 years (95% CI: 4.8-11.0). The remission rates at 3, 5,
      10, and 20 years were 25, 43, 60, and 75%, respectively. Factors influencing
      remission were platelets >60 * 109 /L at the onset of chronic ITP (hazard ratio
      [HR]: 7.24, 95% CI: 3.0-17.5) and treatment with intravenous immunoglobulin (HR:
      0.37, 95% CI: 0.16-0.84). Age, gender, and clinical factors at the time of newly
      diagnosed ITP including bleeding manifestations, onset of symptoms, and history
      of preceding infection and vaccination were not predictive of remission.
      CONCLUSION: The spontaneous complete remission rates of chronic ITP were 43 and
      60% at 5 and 10 years, respectively, and reached 75% at 20 years. A higher
      platelet level at diagnosis of chronic ITP and form of treatment were
      statistically significant indicators for achieving complete remission.

PMID- 28453896
TI  - Clinical and patient-reported outcomes of SPARE - a randomised feasibility study
      of selective bladder preservation versus radical cystectomy.
AB  - OBJECTIVES: To test the feasibility of a randomised trial in muscle-invasive
      bladder cancer (MIBC) and compare outcomes in patients who receive neoadjuvant
      chemotherapy followed by radical cystectomy (RC) or selective bladder
      preservation (SBP), where definitive treatment [RC or radiotherapy (RT)] is
      determined by response to chemotherapy. PATIENTS AND METHODS: SPARE is a
      multicentre randomised controlled trial comparing RC and SBP in patients with
      MIBC staged T2-3 N0 M0, fit for both treatment strategies and receiving three
      cycles of neoadjuvant chemotherapy. Patients were randomised between RC and SBP
      before a cystoscopy after cycle three of neoadjuvant chemotherapy. Patients with
      <=T1 residual tumour received a fourth cycle of neoadjuvant chemotherapy in both
      groups, followed by radical RT in the SBP group and RC in in the RC group; non
      responders in both groups proceeded immediately to RC following cycle three.
      Feasibility study primary endpoints were accrual rate and compliance with
      assigned treatment strategy. The phase III trial was designed to demonstrate non
      inferiority of SBP in terms of overall survival (OS) in patients whose tumours
      responded to neoadjuvant chemotherapy. Secondary endpoints included patient
      reported quality of life, clinician assessed toxicity, loco-regional recurrence
      free survival, and rate of salvage RC after SBP. RESULTS: Trial recruitment was
      challenging and below the predefined target with 45 patients recruited in 30
      months (25 RC; 20 SBP). Non-compliance with assigned treatment strategy was
      frequent, six of the 25 patients (24%) randomised to RC received RT. Long-term
      bladder preservation rate was 11/15 (73%) in those who received RT per protocol.
      OS survival was not significantly different between groups. CONCLUSIONS:
      Randomising patients with MIBC between RC and SBP based on response to
      neoadjuvant chemotherapy was not feasible in the UK health system. Strong
      clinician and patient preferences for treatments impacted willingness to undergo
      randomisation and acceptance of treatment allocation. Due to the few
      participants, firm conclusions about disease and toxicity outcomes cannot be
      drawn.

PMID- 28453898
TI  - Electrophysiological effects of anthracyclines in adult survivors of pediatric
      malignancy.
AB  - BACKGROUND: Anthracycline use is limited by cardiotoxicity, including arrhythmias
      and left ventricular (LV) dysfunction. We aim to characterize the association
      between electrophysiological changes and LV dysfunction. METHODS: A retrospective
      chart review was conducted, including all 147 pediatric cancer survivors at our
      institution over 18 years of age and treated with an anthracycline. One hundred
      thirty-four patients who had at least one electrocardiogram (ECG) and
      echocardiogram were analyzed. The association between dysfunction and baseline
      characteristics, treatment history, and electrocardigraphic parameters were
      analyzed using multivariable logistic regression. Additionally, a longitudinal
      generalized estimating equation (GEE) model was used to examine the temporal
      association between repeated measure corrected QT (QTc) intervals and subsequent
      LV function. RESULTS: In our population, 24% of patients had LV dysfunction. The
      initial posttreatment QTc interval was longer in patients with LV dysfunction
      (438 +/- 35 vs. 420 +/- 20 msec, P = 0.002). In logistic regression analysis, QTc
      interval (P < 0.001) and cumulative radiation dose (P = 0.027) were associated
      with LV dysfunction. On ECGs performed prior to evidence of LV dysfunction, the
      QTc was longer than on ECGs preceding a normal echocardiogram (451 +/- 32 msec
      vs. 423 +/- 25 msec, P < 0.001). Mean time from QTc >= 450 msec to evidence of LV
      dysfunction was 1.8 +/- 2.9 years. In the longitudinal GEE model, QTc
      prolongation was associated with subsequent decreased fractional shortening.
      CONCLUSIONS: Among adult survivors of pediatric cancer treated with
      anthracyclines, prolongation of the QTc interval was associated with subsequent
      LV dysfunction.

PMID- 28453899
TI  - Blood flow after contraction and cuff occlusion is reduced in subjects with
      muscle soreness after eccentric exercise.
AB  - Delayed onset muscle soreness (DOMS) occurs within 1-2 days after eccentric
      exercise, but the mechanism mediating hypersensitivity is unclear. This study
      hypothesized that eccentric exercise reduces the blood flow response following
      muscle contractions and cuff occlusion, which may result in accumulated algesic
      substances being a part of the sensitization in DOMS. Twelve healthy subjects
      (five women) performed dorsiflexion exercise (five sets of 10 repeated eccentric
      contractions) in one leg, while the contralateral leg was the control. The
      maximal voluntary contraction (MVC) of the tibialis anterior muscle was recorded.
      Blood flow was assessed by ultrasound Doppler on the anterior tibialis artery
      (ATA) and within the anterior tibialis muscle tissue before and immediately after
      1-second MVC, 5-seconds MVC, and 5-minutes thigh cuff occlusion. Pressure pain
      thresholds (PPTs) were recorded on the tibialis anterior muscle. All measures
      were done bilaterally at day 0 (pre-exercise), day 2, and day 6 (post-exercise).
      Subjects scored the muscle soreness on a Likert scale for 6 days. Eccentric
      exercise increased Likert scores at day 1 and day 2 compared with day 0 (P<.001).
      Compared with pre-exercise (day 0), reduced PPT (~25%, P<.002), MVC (~22%,
      P<.002), ATA diameter (~8%, P<.002), ATA post-contraction/occlusion blood flow
      (~16%, P<.04), and intramuscular peak blood flow (~23%, P<.03) were found in the
      DOMS leg on day 2 but not in the control leg. These results showed that eccentric
      contractions decreased vessel diameter, impaired the blood flow response, and
      promoted hyperalgesia. Thus, the results suggest that the blood flow reduction
      may be involved in the increased pain response after eccentric exercise.

PMID- 28453900
TI  - The Kinetics of Growth of Metallo-supramolecular Polyelectrolytes in Solution.
AB  - Several transition metal ions, like Fe2+ , Co2+ , Ni2+ , and Zn2+ complex to the
      ditopic ligand 1,4-bis(2,2':6',2''-terpyridin-4'-yl)benzene (L). Due to the high
      association constant, metal-ion induced self-assembly of Fe2+ , Co2+ , and Ni2+
      leads to extended, rigid-rod like metallo-supramolecular coordination
      polyelectrolytes (MEPEs) even in aqueous solution. Here, we present the kinetics
      of growth of MEPEs. The species in solutions are analyzed by light scattering,
      viscometry and cryogenic transmission electron microscopy (cryo-TEM). At near
      stoichiometric amounts of the reactants, we obtained high molar masses, which
      follow the order Ni-MEPE~Co-MEPE<Fe-MEPE. The experiments indicate that the
      kinetics of MEPE growth follows a reversible step-growth mechanism. The forward
      polymerization rate constants follow the order Co-MEPE<Fe-MEPE<Ni-MEPE and the
      growth of MEPEs can be accelerated by adding potassium acetate.

PMID- 28453902
TI  - Lighting up kinase action in platelets.

PMID- 28453901
TI  - Quasi-static acoustic tweezing thromboelastometry.
AB  - : Essentials Blood coagulation measurement during contact with an artificial
      surface leads to unreliable data. Acoustic tweezing thromboelastometry is a novel
      non-contact method for coagulation monitoring. This method detects differences in
      the blood coagulation state within 10 min. Coagulation data were obtained using a
      much smaller sample volume (4 MUL) than currently used. SUMMARY: Background
      Thromboelastography is widely used as a tool to assess the coagulation status of
      critical care patients. It allows observation of changes in material properties
      of whole blood, beginning with early stages of clot formation and ending with
      clot lysis. However, the contact activation of the coagulation cascade at
      surfaces of thromboelastographic systems leads to inherent variability and
      unreliability in predicting bleeding or thrombosis risks. Objectives To develop
      acoustic tweezing thromboelastometry as a non-contact method for perioperative
      assessment of blood coagulation. Methods Acoustic tweezing is used to levitate
      microliter drops of biopolymer and human blood samples. By quasi-statically
      changing the acoustic pressure we control the sample drop location and
      deformation. Sample size, deformation and location are determined by digital
      imaging at each pressure. Results Simple Newtonian liquid solutions maintain a
      constant, reversible location vs. deformation curve. In contrast, the
      location/deformation curves for gelatin, alginate, whole blood and blood plasma
      uniquely change as the samples solidify. Increasing elasticity causes the sample
      to deform less, leading to steeper stress/strain curves. By extracting a linear
      regime slope, we show that whole blood or blood plasma exhibits a unique slope
      profile as it begins to clot. By exposing blood samples to pro- or antithrombotic
      agents, the slope profile changes, allowing detection of hyper- or hypocoagulable
      states. Conclusions We demonstrate that quasi-static acoustic tweezing can yield
      information about clotting onset, maturation and strength. The advantages of
      small sample size, non-contact and rapid measurement make this technique
      desirable for real-time monitoring of blood coagulation.

PMID- 28453903
TI  - Perfusion monitoring and intraventricular hemorrhage in preterm infants.
AB  - Cardiovascular instability in preterm infants during the early postnatal period
      correlates with the development of intraventricular hemorrhage (IVH). Due to the
      correlation between hypotension and fluctuation of blood pressure, treatment was
      targeted specifically at hypotension to prevent IVH, but this was not successful.
      Recently, several novel perfusion markers have been found to be correlated with
      the development of IVH, and they are of current interest in cardiovascular
      management. In this review, the correlation between IVH and conventional, as well
      as novel, perfusion markers is examined.

PMID- 28453904
TI  - Genetics and other factors in the aetiology of female pattern hair loss.
AB  - Pattern hair loss is the most common form of hair loss in both women and men.
      Male pattern hair loss, also termed male androgenetic alopecia (M-AGA), is an
      androgen-dependent trait that is predominantly genetically determined. Androgen
      mediated mechanisms are probably involved in female pattern hair loss (FPHL) in
      some women but the evidence is less strong than in M-AGA; other non-androgenic
      pathways, including environmental influences, may contribute to the aetiology.
      Genome-wide association studies have identified several genetic loci for M-AGA
      and have provided better insight into the underlying biology. However, the role
      of heritable factors in Female Pattern Hair Loss (FPHL) is largely unknown.
      Recently published studies have been restricted to candidate gene approaches and
      could not clearly identify any susceptibility locus/gene for FPHL but suggest
      that the aetiology differs substantially from that of M-AGA. Hypotheses about
      possible pathomechanisms of FPHL as well as the results of the genetic studies
      performed to date are summarized.

PMID- 28453906
TI  - Oral treponeme major surface protein: Sequence diversity and distributions within
      periodontal niches.
AB  - Treponema denticola and other species (phylotypes) of oral spirochetes are widely
      considered to play important etiological roles in periodontitis and other oral
      infections. The major surface protein (Msp) of T. denticola is directly
      implicated in several pathological mechanisms. Here, we have analyzed msp
      sequence diversity across 68 strains of oral phylogroup 1 and 2 treponemes;
      including reference strains of T. denticola, Treponema putidum, Treponema medium,
      'Treponema vincentii', and 'Treponema sinensis'. All encoded Msp proteins
      contained highly conserved, taxon-specific signal peptides, and shared a
      predicted 'three-domain' structure. A clone-based strategy employing 'msp
      specific' polymerase chain reaction primers was used to analyze msp gene sequence
      diversity present in subgingival plaque samples collected from a group of
      individuals with chronic periodontitis (n=10), vs periodontitis-free controls
      (n=10). We obtained 626 clinical msp gene sequences, which were assigned to 21
      distinct 'clinical msp genotypes' (95% sequence identity cut-off). The most
      frequently detected clinical msp genotype corresponded to T. denticola ATCC
      35405T , but this was not correlated to disease status. UniFrac and libshuff
      analysis revealed that individuals with periodontitis and periodontitis-free
      controls harbored significantly different communities of treponeme clinical msp
      genotypes (P<.001). Patients with periodontitis had higher levels of clinical msp
      genotype diversity than periodontitis-free controls (Mann-Whitney U-test, P<.05).
      The relative proportions of 'T. vincentii' clinical msp genotypes were
      significantly higher in the control group than in the periodontitis group
      (P=.018). In conclusion, our data clearly show that both healthy and diseased
      individuals commonly harbor a wide diversity of Treponema clinical msp genotypes
      within their subgingival niches.

PMID- 28453905
TI  - Transdiagnostic neural correlates of affective face processing in anxiety and
      depression.
AB  - BACKGROUND: It is unknown whether there are neurobiologic differences between
      various anxiety and depressive disorders, or whether they are characterized by
      shared neurobiologic variation that cuts across diagnostic boundaries. For
      instance, multiple anxiety disorders and depression may be characterized by
      abnormalities in blood oxygen-level dependent (BOLD) response during the
      processing of affective scenes and faces. To interrogate the shared or unique
      nature of these aberrations, research that examines the influence of
      transdiagnostic, dimensional predictors across multiple diagnoses is needed.
      METHODS: One hundred ninety-nine individuals, 142 with primary diagnoses of
      social anxiety disorder (SAD), generalized anxiety disorder (GAD), or major
      depressive disorder (MDD) and 57 free from psychiatric diagnoses (healthy
      controls, HCs), performed a face-matching task involving fearful, angry, and
      happy faces (and geometric shapes) while undergoing functional magnetic resonance
      imaging. RESULTS: Across the three primary diagnoses, anxiety symptom scores were
      associated with increased Angry > Shapes activation in the bilateral insula,
      anterior/midcingulate, and dorsolateral prefrontal cortex (dlPFC), while
      depressive symptoms were associated with reduced dlPFC activation for Angry >
      Shapes. Patient > HC differences were limited to non a priori regions, and no
      differences in BOLD activation were observed between diagnostic groups.
      CONCLUSIONS: (1) Activation in paralimbic, cingulate, and lateral prefrontal
      regions in response to angry faces is associated with transdiagnostic anxiety and
      depressive symptomatology. (2) Anxiety and depressive symptoms may exert opposing
      influences on lateral prefrontal activation. (3) Abnormal threat processing in
      GAD, SAD, and MDD may reflect shared neural dysfunction that varies with symptom
      load.

PMID- 28453907
TI  - Aggregation Behavior of Non-ionic Twinned Amphiphiles and Their Application as
      Biomedical Nanocarriers.
AB  - A new class of twinned amphiphiles was developed by conjugating a pair of
      hydrophilic head groups from mPEG chains (Mn : 350 or 1000) and a pair of
      hydrophobic segments from linear alkyl chains (C11 or C18 ) through a novel
      spacer synthesized from glycerol and p-hydroxybenzoic acid. The aggregation
      phenomena of the amphiphiles were proven by DLS and fluorescence experiments,
      whereas size and morphology of the aggregates were evaluated by cryo-TEM. The
      measurements proved the formation of globular, thread-like or rod-like micelles
      as well as planar double-layer assemblies, depending on the amphiphile's
      molecular structure. The applicability of these non-ionic amphiphilic systems as
      nanocarriers for hydrophobic guest molecules was demonstrated by encapsulating a
      hydrophobic dye, Nile Red, and a hydrophobic drug, Nimodipine. The transport
      capacity results for both Nimodipine and Nile Red prove them as a promising
      candidate for drug delivery.

PMID- 28453908
TI  - Sexual dysfunction in subjects treated with inhibitors of 5alpha-reductase for
      benign prostatic hyperplasia: a comprehensive review and meta-analysis.
AB  - Despite their efficacy in the treatment of benign prostatic hyperplasia, the
      popularity of inhibitors of 5alpha-reductase (5ARIs) is limited by their
      association with adverse sexual side effects. The aim of this study was to review
      and meta-analyze currently available randomized clinical trials evaluating the
      rate of sexual side effects in men treated with 5ARIs. An extensive Medline
      Embase and Cochrane search was performed including the following words:
      'finasteride', 'dutasteride', 'benign prostatic hyperplasia'. Only placebo
      controlled randomized clinical trials evaluating the effect of 5ARI in subjects
      with benign prostatic hyperplasia were considered. Of 383 retrieved articles, 17
      were included in this study. Randomized clinical trials enrolled 24,463 in the
      active and 22,270 patients in the placebo arms, respectively, with a mean follow
      up of 99 weeks and mean age of 64.0 years. No difference was observed between
      trials using finasteride or dutasteride as the active arm considering age, trial
      duration, prostate volume or International Prostatic Symptoms Score at
      enrollment. Overall, 5ARIs determined an increased risk of hypoactive sexual
      desire [OR = 1.54 (1.29; 1.82); p < 0.0001] and erectile dysfunction [OR = 1.47
      (1.29; 1.68); p < 0.0001]. No difference between finasteride and dutasteride
      regarding the risk of hypoactive sexual desire and erectile dysfunction was
      observed. Meta-regression analysis showed that the risk of hypoactive sexual
      desire and erectile dysfunction was higher in subjects with lower Qmax at
      enrollment and decreased as a function of trial follow-up. Conversely, no effect
      of age, low urinary tract symptom or prostate volume at enrollment as well as
      Qmax at end-point was observed. In conclusion, present data show that the use of
      5ARI significantly increases the risk of erectile dysfunction and hypoactive
      sexual desire in subjects with benign prostatic hyperplasia. Patients should be
      adequately informed before 5ARIs are prescribed.

PMID- 28453909
TI  - Cardiotoxicity and cardiomyopathy in children and young adult survivors of
      hematopoietic stem cell transplant.
AB  - Cardiomyopathy is common in long-term survivors of pediatric hematopoietic stem
      cell transplant (HSCT). Events occurring before and after HSCT when combined with
      specific insults during HSCT likely contribute to long-term risk. Strategies for
      detecting subclinical cardiomyopathy prior to patients developing overt heart
      failure are under investigation. Changes in HSCT preparative regimens and
      cardioprotective medications administered during chemotherapy may alter the risk
      for cardiomyopathy. Interventions in long-term survivors such as lifestyle
      modification and cardioactive medications are of increasing importance. Herein we
      review the causes of cardiac injury, discuss strategies for detection of
      cardiomyopathy, and evaluate therapeutic options for long-term HSCT survivors.

PMID- 28453910
TI  - Central nervous system disease in pediatric acute myeloid leukemia: A report from
      the Children's Oncology Group.
AB  - BACKGROUND: The prognostic impact of central nervous system (CNS) involvement in
      children with acute myeloid leukemia (AML) has varied in past trials, and
      controversy exists over the degree of involvement requiring intensified CNS
      therapy. Two recent Children's Oncology Group protocols, AAML03P1 and AAML0531,
      directed additional intrathecal (IT) therapy to patients with CNS2 (<=5 white
      blood cell [WBC] with blasts) or CNS3 (>5 WBC with blasts or CNS symptoms)
      disease at diagnosis. METHODS: We examined disease characteristics and outcomes
      of the 1,344 patients on these protocols, 949 with CNS1 (no blasts), 217 with
      CNS2, and 178 with CNS3, with the latter two receiving additional IT therapy.
      RESULTS: Young age (P = 0.003), hyperleukocytosis (P < 0.001), and the presence
      of inversion 16 (P < 0.001) were the only factors more prevalent in patients with
      CNS2 or CNS3 disease. Complete remission at the end of induction (EOI) 2 was
      achieved less often in patients with CNS involvement (P < 0.001). From diagnosis,
      event-free survival (EFS) for patients with CNS involvement was significantly
      worse (P < 0.001), whereas overall survival (OS) was not (P = 0.16). From the
      EOI1, there was a higher relapse rate (RR) and worse disease-free survival (DFS),
      but less impact on OS (CNS1:DFS 58.9%, RR 34.1%, OS 69.3%; CNS2:DFS 53.2%, RR
      40.9%, OS 74.7%; CNS3:DFS 45.2%, RR 48.8%, OS 60.8%; P = 0.006, P < 0.001, P =
      0.045, respectively). Multivariable analysis showed that independently CNS2 and
      CNS3 status adversely affected RR and DFS. Traumatic diagnostic lumbar puncture
      was not associated with worse outcome. CONCLUSIONS: CNS leukemia confers greater
      relapse risk despite more aggressive locally directed therapy. Novel approaches
      need to be investigated in this group of patients.

PMID- 28453911
TI  - Validation of biomechanical deformable image registration in the abdomen, thorax,
      and pelvis in a commercial radiotherapy treatment planning system.
AB  - PURPOSE: The accuracy of deformable image registration tools can vary widely
      between imaging modalities and specific implementations of the same algorithms. A
      biomechanical model-based algorithm initially developed in-house at an academic
      institution was translated into a commercial radiotherapy treatment planning
      system and validated for multiple imaging modalities and anatomic sites. METHODS:
      Biomechanical deformable registration (Morfeus) is a geometry-driven algorithm
      based on the finite element method. Boundary conditions are derived from the
      model-based segmentation of controlling structures in each image which
      establishes a point-to-point surface correspondence. For each controlling
      structure, material properties and fixed or sliding interfaces are assigned. The
      displacements of internal volumes for controlling structures and other structures
      implicitly deformed are solved with finite element analysis. Registration was
      performed for 74 patients with images (mean vector resolution) of thoracic and
      abdominal 4DCT (2.8 mm) and MR (5.3 mm), liver CT-MR (4.5 mm), and prostate MR
      (2.6 mm). Accuracy was quantified between deformed and actual target images using
      distance-to-agreement (DTA) for structure surfaces and the target registration
      error (TRE) for internal point landmarks. RESULTS: The results of the commercial
      implementation were as follows. The mean DTA was <= 1.0 mm for controlling
      structures and 1.0-3.5 mm for implicitly deformed structures on average. TRE
      ranged from 2.0 mm on prostate MR to 5.1 mm on lung MR on average, within 0.1 mm
      or lower than the image voxel sizes. Accuracy was not overly sensitive to changes
      in the material properties or variability in structure segmentations, as changing
      these inputs affected DTA and TRE by <= 0.8 mm. Maximum DTA > 5 mm occurred for
      88% of the structures evaluated although these were within the inherent
      segmentation uncertainty for 82% of structures. Differences in accuracy between
      the commercial and in-house research implementations were <= 0.5 mm for mean DTA
      and <= 0.7 mm for mean TRE. CONCLUSIONS: Accuracy of biomechanical deformable
      registration evaluated on a large cohort of images in the thorax, abdomen and
      prostate was similar to the image voxel resolution on average across multiple
      modalities. Validation of this treatment planning system implementation supports
      biomechanical deformable registration as a versatile clinical tool to enable
      accurate target delineation at planning and treatment adaptation.

PMID- 28453913
TI  - Bioprinting of biomimetic skin containing melanocytes.
AB  - This study reports a three-dimensional (3D) bioprinting technique that is capable
      of producing a full-thickness skin model containing pigmentation. Multiple layers
      of fibroblast (FB)-containing collagen hydrogel precursor were printed and
      crosslinked through neutralization using sodium bicarbonate, constituting the
      dermal layer. Melanocytes (MCs) and keratinocytes (KCs) were sequentially printed
      on top of the dermal layer to induce skin pigmentation upon subsequent air-liquid
      interface culture. Histological analysis was performed not only to confirm the
      formation of distinct skin layers, but also to identify the presence of
      pigmentation. The bioprinted skin structure showed the dermal and epidermal
      layers as well as the terminal differentiation of the KC that formed the stratum
      corneum. Moreover, the MC-containing epidermal layer showed freckle-like
      pigmentations at the dermal-epidermal junction, without the use of external
      ultraviolet light or chemical stimuli. The presented method offers the capability
      of producing engineered ephelides in biomimetic skin, thus rendering 3D
      bioprinting techniques as productive on-demand options for the creation of skin
      models available for therapeutic or research use.

PMID- 28453912
TI  - Perceived need for depression treatment among persons entering inpatient opioid
      detoxification.
AB  - BACKGROUND AND OBJECTIVES: Depression is common among persons with opioid use
      disorder. We examined the perceived need for depression treatment (PNDT) among
      opioid-dependent patients and the relationship of PNDT to depression screening
      result. METHODS: Between May and December 2015, we surveyed consecutive persons
      (n = 440) seeking inpatient opioid detoxification. We used the Patient Health
      Questionnaire-2 (PHQ-2) to screen for depression. To assess perceived need for
      depression services, participants were asked, "Do you believe you should be
      treated for depression?" Response options were recorded into four categories:
      "Not Depressed (ND)," "Perceive Need for Depression Treatment (PNDT),"
      "Depressed/Don't Want Treatment," and "Currently Treated." RESULTS: Participants'
      mean age was 32.3 (+/-8.7) years; 70.7% were male. Nearly two out of three
      persons screened positive for depression yet only 8.2% were being treated for
      depression prior to admission. Screening positive for depression was associated
      with a 2.95 (95%CI 1.82-4.81, p < .005) fold increase in the expected odds of
      PNDT. But nearly half of those depressed (48%) did not perceive the need for
      treatment. Approximately 40% of the participants (n = 177) perceived that they
      were not depressed; of these persons, 52% screened positive for depression.
      DISCUSSION AND CONCLUSIONS: Detoxification program staff should screen patients
      for depression, and if a clinical diagnosis is confirmed, discuss treatment
      options, exploring the level of interest in mental health treatment for
      depression. SCIENTIFIC SIGNIFICANCE: Screening for and addressing depression,
      including patients' interest in treatment, should be central to post
      detoxification aftercare planning. (Am J Addict 2017;26:395-399).

PMID- 28453914
TI  - The Shape of Things To Come: The Formation of Modulated Nematic Mesophases at
      Various Length Scales.
AB  - The twist-bend nematic (NTB ) phase is a recently discovered liquid-crystalline
      phase that exhibits macroscopic chirality even when formed from achiral
      materials, and as such presents a unique testbed for studies concerning the
      spontaneous breaking of mirror symmetry in soft matter. It is primarily exhibited
      by materials for which the molecular structure is composed of two rigid aromatic
      units (such as biphenyl connected by a flexible spacer). The local structure of
      the NTB phase is nematic-like-with molecules having an average orientational
      order but no positional order-with a nanoscale helix in which the pitch (i.e.,
      the repeat distance of the helix) is of the order of several nanometres. A helix
      is chiral, and so the bulk NTB phase-in the absence of a biasing chiral
      environment-spontaneously separates into macroscopic domains of opposite
      handedness. After discussing the structure of this mesophase and its elucidation,
      this concept article presents the molecular factors that determine its incidence.
      The apparent dependency primarily on molecular shape and bend angle rather than
      particular functional group combinations manifests in this mesophase being
      exhibited on length scales far beyond those of simple liquid-crystalline dimers,
      not only in oligomers and polymers, but also in aqueous suspensions of micron
      sized helical particles.

PMID- 28453915
TI  - Documenting and harnessing the biological potential of molecules in Distributed
      Drug Discovery (D3) virtual catalogs.
AB  - Virtual molecular catalogs have limited utility if member compounds are (i)
      difficult to synthesize or (ii) unlikely to have biological activity. The
      Distributed Drug Discovery (D3) program addresses the synthesis challenge by
      providing scientists with a free virtual D3 catalog of 73,024 easy-to-synthesize
      N-acyl unnatural alpha-amino acids, their methyl esters, and primary amides. The
      remaining challenge is to document and exploit the bioactivity potential of these
      compounds. In the current work, a search process is described that
      retrospectively identifies all virtual D3 compounds classified as bioactive hits
      in PubChem-cataloged experimental assays. The results provide insight into the
      broad range of drug-target classes amenable to inhibition and/or agonism by D3
      accessible molecules. To encourage computer-aided drug discovery centered on
      these compounds, a publicly available virtual database of D3 molecules prepared
      for use with popular computer docking programs is also presented.

PMID- 28453918
TI  - Value of brush cytology for optimal timing of liver transplantation in primary
      sclerosing cholangitis.
AB  - BACKGROUND AND AIMS: Primary sclerosing cholangitis is associated with a high
      risk of cholangiocarcinoma. Here, we investigated the value of surveillance for
      dysplasia using brush cytology, to determine the optimal timing of liver
      transplantation in primary sclerosing cholangitis. We compared our preoperative
      findings, with the final explanted liver histopathology. METHODS: 126 consecutive
      patients were transplanted for primary sclerosing cholangitis from 1984 to 2012.
      Patients were divided into two groups: symptomatic (n=91), and asymptomatic
      (n=35). RESULTS: Brush cytology was available for 101 patients; 66 symptomatic
      and 35 asymptomatic. Suspicious cytological findings were found in nine patients
      (14%) in the symptomatic group and 17 (49%) in the asymptomatic group. DNA flow
      cytometry was available for 49 patients (25 symptomatic, 24 asymptomatic), with
      aneuploidy detected in six patients (24%) in the symptomatic group and 15 (63%)
      in the asymptomatic group. Explanted liver histology showed biliary dysplasia or
      cholangiocarcinoma in 11 symptomatic patients (12%) and 15 asymptomatic patients
      (43%). A combination of cytological and DNA flow cytometry findings resulted in a
      test sensitivity of 68%, with a specificity of 86%. Ten-year survival in the
      asymptomatic group was 91%. CONCLUSIONS: Dysplasia surveillance using brush
      specimens may help to select those patients likely to benefit from early liver
      transplantation. It remains unclear as to whether surveillance with brush
      cytology improves long-term survival, but there is presently no better method
      with which to predict transplantation timing.

PMID- 28453919
TI  - Editor's Note.

PMID- 28453916
TI  - Digital technology and clinical decision making in depression treatment: Current
      findings and future opportunities.
AB  - Clinical decision making encompasses a broad set of processes that contribute to
      the effectiveness of depression treatments. There is emerging interest in using
      digital technologies to support effective and efficient clinical decision making.
      In this paper, we provide "snapshots" of research and current directions on ways
      that digital technologies can support clinical decision making in depression
      treatment. Practical facets of clinical decision making are reviewed, then
      research, design, and implementation opportunities where technology can
      potentially enhance clinical decision making are outlined. Discussions of these
      opportunities are organized around three established movements designed to
      enhance clinical decision making for depression treatment, including measurement
      based care, integrated care, and personalized medicine. Research, design, and
      implementation efforts may support clinical decision making for depression by (1)
      improving tools to incorporate depression symptom data into existing electronic
      health record systems, (2) enhancing measurement of treatment fidelity and
      treatment processes, (3) harnessing smartphone and biosensor data to inform
      clinical decision making, (4) enhancing tools that support communication and care
      coordination between patients and providers and within provider teams, and (5)
      leveraging treatment and outcome data from electronic health record systems to
      support personalized depression treatment. The current climate of rapid changes
      in both healthcare and digital technologies facilitates an urgent need for
      research, design, and implementation of digital technologies that explicitly
      support clinical decision making. Ensuring that such tools are efficient,
      effective, and usable in frontline treatment settings will be essential for their
      success and will require engagement of stakeholders from multiple domains.

PMID- 28453920
TI  - Papers based on data concerning organs from executed prisoners should not be
      published: Response to Zheng and Yan.

PMID- 28453921
TI  - Response to Real life Egyptian experience of efficacy / safety of Simeprevir?
      Sofosbuvir in HCV genotype IV.

PMID- 28453922
TI  - Predictive models for recurrence risk of hepatocellular carcinoma after liver
      transplantation: Still an unmet need.

PMID- 28453923
TI  - Liver transplant in acute-on-chronic liver failure: Evaluating the impact of
      organ dysfunction.

PMID- 28453924
TI  - Correlates of Common Mental Disorders Among Dutch Women Who Have Had an Abortion:
      A Longitudinal Cohort Study.
AB  - CONTEXT: Credible research has not found any evidence that abortion causes mental
      disorders. It is not known, however, whether abortion-specific risk indicators
      and other variables are associated with the incidence or recurrence of mental
      disorders after abortion. METHODS: As part of a prospective cohort study
      conducted in the Netherlands, 325 women were interviewed between April 2010 and
      January 2011, between 20 and 40 days after having an abortion; 264 were followed
      up an average of 2.7 years later. Associations between selected baseline
      variables and postabortion incident or recurrent mental disorders among the 199
      women at risk were investigated using bivariate and multivariate logistic
      regression analyses. RESULTS: Thirty-two percent of women at risk of an incident
      or recurrent mental disorder experienced one after the abortion. In multivariate
      analyses, no abortion-related variables (e.g., history of multiple abortions,
      second-trimester abortion, preabortion decision difficulty or uncertainty, and
      postabortion negative emotions) were associated with experience of any
      postabortion incident or recurrent mental disorders. The outcome was positively
      associated with having conceived within an unstable relationship (odds ratio,
      3.0), number of negative life events in the past year (1.4) and having a history
      of mental disorders (2.4). CONCLUSIONS: Correlates of postabortion mental
      disorders were variables that have been identified as general risk factors for
      mental disorders, which supports the idea that abortion does not pose specific
      risks to future mental health. Future research should investigate in what way
      unstable relationships, adverse life events and psychiatric history affect
      postabortion mental health.

PMID- 28453925
TI  - PKCiota is a target of 7,8,4'-trihydroxyisoflavone for the suppression of UVB
      induced MMP-1 expression.
AB  - The soy isoflavone daidzein is bioconverted to 7,8,4'-trihydroxyisoflavone
      (7,8,4'-THIF) by microorganisms. Here, we investigated the matrix
      metalloproteinase (MMP)-1 inhibitory properties of 7,8,4'-THIF that arise through
      the suppression of UVB-induced MMP-1 expression. 7,8,4'-THIF reduced UVB-induced
      MMP-1 expression at the transcriptional level in primary human dermal fibroblasts
      and inhibited UVB-induced transcriptional activity of AP-1, a major activator of
      MMP-1 expression. Additionally, it was observed that the mitogen-activated
      protein kinase (MAPK) pathway, a crucial signalling cascade for MMP-1 expression,
      was suppressed by 7,8,4'-THIF. Protein kinase C iota (PKCiota) was suspected to
      be a direct target of 7,8,4'-THIF. The direct interaction between 7,8,4'-THIF and
      PKCiota was confirmed using pull-down assays and immobilized metal ion affinity
      based fluorescence polarization assays. Finally, we observed that 7,8,4'-THIF
      inhibited UVB-induced MMP-1 expression in a human skin equivalent model. Taken
      together, these results suggest that 7,8,4'-THIF, a bioconversion product of
      daidzein, suppresses UVB-induced MMP-1 expression.

PMID- 28453926
TI  - Fluoropolymer-Stabilized Chromophore-Catalyst Assemblies in Aqueous Buffer
      Solutions for Water-Oxidation Catalysis.
AB  - Here, the application of the fluorinated polymer [Dupont AF, a copolymer of 4,5
      difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole and tetrafluoroethylene] is
      described in stabilizing phosphonate-derivatized molecular assemblies on oxide
      electrodes. In the procedure, the polymer was dip-coated onto the surfaces of
      oxide electrodes with pre-bound, phosphonate-derivatized chromophores and
      assemblies, including assemblies for water oxidation. The results of the
      experiments showed a high degree of stabilization by the added polymer and a
      demonstration of its use in stabilizing surface-bound assemblies for water
      oxidation catalysis.

PMID- 28453927
TI  - TIR-domain-containing adapter-inducing interferon-beta (TRIF) forms filamentous
      structures, whose pro-apoptotic signalling is terminated by autophagy.
AB  - The formation of amyloid-like protein structures has recently emerged as a
      feature in signal transduction, particularly in innate immunity. These structures
      appear to depend on defined domains for their formation but likely also require
      dedicated ways to terminate signalling. We, here, define the innate immunity
      protein/Toll-like receptor adaptor TIR-domain-containing adapter-inducing
      interferon-beta (TRIF) as a novel platform of fibril formation and probe signal
      initiation through TRIF as well as its termination in Toll-like receptor 3 (TLR3)
      stimulated melanoma cells. A main signalling pathway triggered by TLR3 caused
      apoptosis, which was controlled by inhibitor of apoptosis proteins and was
      dependent on RIPK1 and independent of TNF. Using correlative
      electron/fluorescence microscopy, we visualised fibrillar structures formed
      through both Toll/interleukin-1 receptor and RIP homotypic interacting motif
      regions of TRIF. We provide evidence that these fibrillary structures are active
      signalling platforms whose activity is terminated by autophagy. TRIF-signalling
      enhanced autophagy, and fibrillary structures were partly contained within
      autophagosomes. Inhibition of autophagy increased levels of pro-apoptotic TRIF
      complexes, leading to the accumulation of active caspase-8 and enhanced apoptosis
      while stimulation of autophagy reduced TRIF-dependent death. We conclude that pro
      death signals through TRIF are regulated by autophagy and propose that pro
      apoptotic signalling through TRIF/RIPK1/caspase-8 occurs in fibrillary platforms.

PMID- 28453928
TI  - The clinical severity of hemoglobin S/Black (A gammadeltabeta)0 -thalassemia.
AB  - Hemoglobin S/Black (A gammadeltabeta)0 -thalassemia is a rare sickle cell disease
      (SCD) variant. On the basis of limited descriptions in the literature, the
      disease is reported as a mild microcytic anemia with an uncomplicated course. We
      report the clinical and laboratory data of nine patients whose diagnoses were
      confirmed by DNA-based techniques. Despite having mild anemia and high fetal
      hemoglobin level postinfancy, these patients developed many of the classic
      complications of SCD, including vaso-occlusive crisis, acute chest syndrome,
      avascular necrosis, and cholelithiasis. On the basis of these findings, we
      recommend that patients with this rare disorder receive specialized hematology
      care according to SCD guidelines.

PMID- 28453929
TI  - Synthesis of Lipophilic Core-Shell Fe3O4@SiO2@Au Nanoparticles and Polymeric
      Entrapment into Nanomicelles: A Novel Nanosystem for in Vivo Active Targeting and
      Magnetic Resonance-Photoacoustic Dual Imaging.
AB  - In this work, iron/silica/gold core-shell nanoparticles (Fe3O4@SiO2@Au NPs)
      characterized by magnetic and optical properties have been synthesized to obtain
      a promising theranostic platform. To improve their biocompatibility, the obtained
      multilayer nanoparticles have been entrapped in polymeric micelles, decorated
      with folic acid moieties, and tested in vivo for photoacoustic and magnetic
      resonance imaging detection of ovarian cancer.

PMID- 28453930
TI  - The APOE epsilon4 Allele Is Associated with Lower Selenium Levels in the Brain:
      Implications for Alzheimer's Disease.
AB  - The antioxidant activity of selenium, which is mainly conferred by its
      incorporation into dedicated selenoproteins, has been suggested as a possible
      neuroprotective approach for mitigating neuronal loss in Alzheimer's disease.
      However, there is inconsistent information with respect to selenium levels in the
      Alzheimer's disease brain. We examined the concentration and cellular
      compartmentalization of selenium in the temporal cortex of Alzheimer's disease
      and control brain tissue. We found that Alzheimer's disease was associated with
      decreased selenium concentration in both soluble (i.e., cytosolic) and insoluble
      (i.e., plaques and tangles) fractions of brain homogenates. The presence of the
      APOE epsilon4 allele correlated with lower total selenium levels in the temporal
      cortex and a higher concentration of soluble selenium. Additionally, we found
      that age significantly contributed to lower selenium concentrations in the
      peripheral membrane-bound and vesicular fractions. Our findings suggest a
      relevant interaction between APOE epsilon4 and selenium delivery into brain, and
      show changes in cellular selenium distribution in the Alzheimer's disease brain.

PMID- 28453931
TI  - Ugi Reaction-Derived alpha-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3
      Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce
      Apoptosis in Multiple Myeloma Cells.
AB  - Heat shock transcription factor 1 (HSF1) has been identified as a therapeutic
      target for pharmacological treatment of multiple myeloma (MM). However, direct
      therapeutic targeting of HSF1 function seems to be difficult due to the shortage
      of clinically suitable pharmacological inhibitors. We utilized the Ugi
      multicomponent reaction to create a small but smart library of alpha-acyl
      aminocarboxamides and evaluated their ability to suppress heat shock response
      (HSR) in MM cells. Using the INA-6 cell line as the MM model and the strictly
      HSF1-dependent HSP72 induction as a HSR model, we identified potential HSF1
      inhibitors. Mass spectrometry-based affinity capture experiments with biotin
      linked derivatives revealed a number of target proteins and complexes, which
      exhibit an armadillo domain. Also, four members of the tumor-promoting and HSF1
      associated phosphatidylinositol 3-kinase-related kinase (PIKK) family were
      identified. The antitumor activity was evaluated, showing that treatment with the
      anti-HSF1 compounds strongly induced apoptotic cell death in MM cells.

PMID- 28453932
TI  - A Green Route to a Na2FePO4F-Based Cathode for Sodium Ion Batteries of High Rate
      and Long Cycling Life.
AB  - Sodium ion batteries (SIBs) are considered one of the most promising alternatives
      for large-scale energy storage due largely to the abundance and low cost of
      sodium. However, the lack of high-performance cathode materials at low cost
      represents a major obstacle toward broad commercialization of SIB technology. In
      this work, we report a green route strategy that allows cost-effective
      fabrication of carbon-coated Na2FePO4F cathode for SIBs. By using vitamin C as a
      green organic carbon source and environmentally friendly water-based polyacrylic
      latex as the binder, we have demonstrated that the Na2FePO4F phase in the as
      derived Na2FePO4F/C electrode shows a high reversible capacity of 117 mAh g-1 at
      a cycling rate of 0.1 C. More attractively, excellent rate capability is achieved
      while retaining outstanding cycling stability (~85% capacity retention after 1000
      charge-discharge cycles at a rate of 4 C). Further, in operando X-ray diffraction
      has been used to probe the evolution of phase structures during the charge
      discharge process, confirming the structural robustness of the Na2FePO4F/C
      cathode (even when charged to 4.5 V). Accordingly, the poor initial Coulombic
      efficiency of some anode materials may be compensated by extracting more sodium
      ions from Na2FePO4F/C cathode at higher potentials (up to 4.5 V).

PMID- 28453933
TI  - Computational Fluid Dynamics Studies of a Flow Reactor: Free Energies of Clusters
      of Sulfuric Acid with NH3 or Dimethyl Amine.
AB  - Computational fluid dynamics simulations of a flow reactor provided 3D spatial
      distributions of its temperature and flow profiles and abundances of sulfuric
      acid, nitrogeneous base, and the acid-base clusters formed from them. Clusters
      were simulated via their kinetic formation and decomposition involving sulfuric
      acid and base molecules. Temperature and flow profiles and the base and sulfuric
      acid distributions are characterized and the latter is compared to mass
      spectrometer measurements. Concentrations of simulated clusters of sulfuric acid
      with either NH3 or dimethylamine were compared to experimentally measured
      particle concentrations. Cluster thermodynamics were adjusted to better the
      agreement between simulated and experimental results. Free energies of acid-base
      clusters derived here are also compared to recent quantum chemistry calculations.
      Sensitivities to the thermodynamics were explored with a 2D laminar flow
      simulation and the abundance of large clusters was most sensitive to the
      thermodynamics of the smallest cluster, consisting of 1 base and 1 acid.
      Comparisons of this model to the computational fluid dynamics models provide
      verification of the implemented cluster chemistry. A box model was used to
      calculate nucleation rates for the conditions of other experimental work, and to
      provide predictions of nucleation for typical atmospheric conditions.

PMID- 28453934
TI  - Generalized Self-Energy Embedding Theory.
AB  - Ab initio quantum chemistry calculations for systems with large active spaces are
      notoriously difficult and cannot be successfully tackled by standard methods. We
      generalize a Green's function QM/QM embedding method called self-energy embedding
      theory (SEET) that has the potential to be successfully employed to treat large
      active spaces. In generalized SEET, active orbitals are grouped into intersecting
      groups of a few orbitals, allowing us to perform multiple parallel calculations
      yielding results comparable to the full active-space treatment. We examine
      generalized SEET on a series of examples and discuss a hierarchy of
      systematically improvable approximations.

PMID- 28453935
TI  - Synthesis of Trialkylhydroxylamines by Stepwise Reduction of O-Acyl N,N
      Disubstituted Hydroxylamines: Substituent Effects on the Reduction of O-(1
      Acyloxyalkyl)hydroxylamines and on the Conformational Dynamics of N
      Alkoxypiperidines.
AB  - The influence of the electron-withdrawing azide group on the reduction of O-(1
      acyloxy-omega-azido)hydroxylamines by triethylsilane in the presence of boron
      trifluoride etherate is studied and found to increase with increasing proximity
      to the reaction site, suggesting that the reaction proceeds by way of
      aminoxocarbenium ion intermediates. The ability to carry azides through the
      reaction sequence affords O-(omega-azidoalkyl-N,N-dialkylhydroxylamines thereby
      making such functionality available for use in click chemistry. A series of 4
      substituted N-alkoxypiperidines were prepared and studied by variable temperature
      NMR spectroscopy leading to the conclusion that the rate-determining step in the
      stereomutation of such piperidines is the piperidine ring flip and not nitrogen
      inversion or rotation about the N-O bond. The process of N-O bond rotation only
      becomes rate determining when in the presence of pervasive steric hindrance as is
      the case with the N-alkoxy-2,2,6,6-tetramethylpiperidines.

PMID- 28453936
TI  - Metallic Twin Grain Boundaries Embedded in MoSe2 Monolayers Grown by Molecular
      Beam Epitaxy.
AB  - Twin grain boundaries in MoSe2 are metallic and undergo a metal to insulator
      Peierls transition at low temperature. Growth of MoSe2 by molecular beam epitaxy
      results in the spontaneous formation of a high density of these twin grain
      boundaries, likely as a mechanism to incorporate Se deficiency in the film. Using
      scanning tunneling microscopy, we study the grain boundary network that is formed
      in homoepitaxially grown MoSe2 and for MoSe2 grown heteroepitaxially on MoS2 and
      HOPG substrates. No statistically relevant variation of the grain boundary
      concentration has been found for the different substrates, indicating that the
      grain boundary formation is substrate independent and depends mainly on the
      growth conditions. Twin grain boundaries exhibit three crystallographically
      identical orientations, and thus they form an intersecting network. Different
      intersection geometries are identified that imply varying defect configurations.
      These intersection points act as preferential nucleation sites for vapor
      deposited metal atoms, which we demonstrate on the example of selective gold
      cluster formation at grain boundary intersections. Scanning tunneling
      spectroscopy shows a band gap narrowing of MoSe2 in the immediate vicinity of the
      metallic grain boundary, which may be associated with lattice strain induced at
      the grain boundary. Tunneling noise spectra taken over the grain boundaries
      indicate random telegraphic noise, suggestive of pinning/depinning behavior of
      conductive channels in the metallic grain boundaries or their intersection
      points. Finally, indications for incommensurate and commensurate Peierls-driven
      charge density wave formation were observed in microprobe transport measurements
      at 205 and 227 K, respectively.

PMID- 28453937
TI  - Impact of Dielectric Constant on the Singlet-Triplet Gap in Thermally Activated
      Delayed Fluorescence Materials.
AB  - Thermally activated delayed fluorescence (TADF) relies on the presence of a very
      small energy gap, DeltaEST, between the lowest singlet and triplet excited
      states. DeltaEST is thus a key factor in the molecular design of more efficient
      materials. However, its accurate theoretical estimation remains challenging,
      especially in the solid state due to the influence of polarization effects. We
      have quantitatively studied DeltaEST as a function of dielectric constant,
      epsilon, for four representative organic molecules using the methodology we
      recently proposed at the Tamm-Dancoff approximation omegaB97X level of theory,
      where the range-separation parameter omega is optimized with the polarizable
      continuum model. The results are found to be in very good agreement with
      experimental data. Importantly, the polarization effects can lead to a marked
      reduction in the DeltaEST value, which is favorable for TADF applications. This
      DeltaEST decrease in the solid state is related to the hybrid characters of the
      lowest singlet and triplet excited states, whose dominant contribution switches
      to charge-transfer-like with increasing epsilon. The present work provides a
      theoretical understanding on the influence of polarization effect on the singlet
      triplet gap and confirms our methodology to be a reliable tool for the prediction
      and development of novel TADF materials.

PMID- 28453938
TI  - Simulated Force Quench Dynamics Shows GB1 Protein Is Not a Two State Folder.
AB  - Single molecule force spectroscopy is a useful technique for investigating
      mechanically induced protein unfolding and refolding under reduced forces by
      monitoring the end-to-end distance of the protein. The data is often interpreted
      via a "two-state" model based on the assumption that the end-to-end distance
      alone is a good reaction coordinate and the thermodynamic behavior is then
      ascribed to the free energy as a function of this one reaction coordinate. In
      this paper, we determined the free energy surface (PMF) of GB1 protein from
      atomistic simulations in explicit solvent under different applied forces as a
      function of two collective variables (the end-to-end-distance, and the fraction
      of native contacts rho). The calculated 2-d free energy surfaces exhibited
      several distinct states, or basins, mostly visible along the rho coordinate.
      Brownian dynamics (BD) simulations on the smoothed free energy surface show that
      the protein visits a metastable molten globule state and is thus a three state
      folder, not the two state folder inferred using the end-to-end distance as the
      sole reaction coordinate. This study lends support to recent experiments that
      suggest that GB1 is not a two-state folder.

PMID- 28453939
TI  - All-Atom Molecular Dynamics Simulations of Peptide Amphiphile Assemblies That
      Spontaneously Form Twisted and Helical Ribbon Structures.
AB  - Self-assembly of peptide amphiphiles (PAs) has been an active research area as
      the assemblies can be programmed into variously shaped nanostructures. Although
      cylindrical micelles are common structures, gold-binding peptide conjugates can
      self-assemble into chiral nanofibers with single or double helices. When gold
      nanoparticles bind to the helices, the resulting chiral nanoparticle assemblies
      have a collective plasmonic circular dichroism signal that can serve as nanoscale
      circular polarizers or chiroptical sensors. A better atomic-level understanding
      of the factors which lead to helical PA assemblies is therefore of significant
      importance. In this study we show that all-atom molecular dynamics simulations
      can describe the spontaneous structural transformation from a planar assembly of
      PAs to a twisted assembly or to a helical ribbon. The twist angle and the helical
      diameter calculated from the simulations closely match the experimental results,
      with the oxidation of a single Met residue in each PA leading to a change from
      bilayer to monolayer assemblies with significantly different ribbon properties. A
      secondary structure analysis shows how a combination of beta-sheet formation near
      the hydrophobic core of the micelle and PPII structures from proline-rich C
      terminus regions favors helix formation. The simulations presented here
      demonstrate the capability of predicting self-assembly in chiral structures,
      protocols that can easily be applied to the assembly of other amphiphilic
      molecules.

PMID- 28453940
TI  - Competition between Hydrogen Evolution and Carbon Dioxide Reduction on Copper
      Electrodes in Mildly Acidic Media.
AB  - Understanding the competition between hydrogen evolution and CO2 reduction is of
      fundamental importance to increase the faradaic efficiency for electrocatalytic
      CO2 reduction in aqueous electrolytes. Here, by using a copper rotating disc
      electrode, we find that the major hydrogen evolution pathway competing with CO2
      reduction is water reduction, even in a relatively acidic electrolyte (pH 2.5).
      The mass-transport-limited reduction of protons takes place at potentials for
      which there is no significant competition with CO2 reduction. This selective
      inhibitory effect of CO2 on water reduction, as well as the difference in onset
      potential even after correction for local pH changes, highlights the importance
      of differentiating between water reduction and proton reduction pathways for
      hydrogen evolution. In-situ FTIR spectroscopy indicates that the adsorbed CO
      formed during CO2 reduction is the primary intermediate responsible for
      inhibiting the water reduction process, which may be one of the main mechanisms
      by which copper maintains a high faradaic efficiency for CO2 reduction in neutral
      media.

PMID- 28453941
TI  - Probing Molecular Interactions between Human Carbonic Anhydrases (hCAs) and a
      Novel Class of Benzenesulfonamides.
AB  - On the basis of X-ray crystallographic studies of the complex of hCA II with 4
      (3,4-dihydro-1H-isoquinoline-2-carbonyl)benzenesulfonamide (3) (PDB code 4Z1J ),
      a novel series of 4-(1-aryl-3,4-dihydro-1H-isoquinolin-2
      carbonyl)benzenesulfonamides (23-33) was designed. Specifically, our idea was to
      improve the selectivity toward druggable isoforms through the introduction of
      additional hydrophobic/hydrophilic functionalities. Among the synthesized and
      tested compounds, the (R,S)-4-(6,7-dihydroxy-1-phenyl-3,4-tetrahydroisoquinoline
      1H-2-carbonyl)benzenesulfonamide (30) exhibited a remarkable inhibition for the
      brain-expressed hCA VII (Ki = 0.20 nM) and selectivity over wider distributed hCA
      I and hCA II isoforms. By enantioselective HPLC, we solved the racemic mixture
      and ascertained that the two enantiomers (30a and 30b) are equiactive inhibitors
      for hCA VII. Crystallographic and docking studies revealed the main interactions
      of these inhibitors into the carbonic anhydrase (CA) catalytic site, thus
      highlighting the relevant role of nonpolar contacts for this class of hCA
      inhibitors.

PMID- 28453942
TI  - Enzymatic Production of Melibiose from Raffinose by the Levansucrase from
      Leuconostoc mesenteroides B-512 FMC.
AB  - Melibiose, which is an important reducing disaccharide formed by alpha-1,6
      linkage between galactose and glucose, has been proven to have beneficial
      applications in both medicine and agriculture. In this study, a characterized
      levansucrase from Leuconostoc mesenteroides B-512 FMC was further used to study
      the bioproduction of melibiose from raffinose. The reaction conditions were
      optimized for melibiose synthesis. The optimal pH, temperature, substrate
      concentration, ratio of substrates, and units of enzymes were determined as pH
      6.0, 45  degrees C, 210 g/L, 1:1 (210 g/L:210 g/L), and 5 U/mL, respectively. The
      transfructosylation product of raffinose was determined to be melibiose by FTIR
      and NMR. A high raffinose concentration was found to strongly favor the
      production of melibiose. When 210 g/L raffinose and 210 g/L lactose were
      catalyzed using 5 U/mL purified levansucrase at pH 6.0 and 45  degrees C, the
      maximal yield of melibiose was 88 g/L.

PMID- 28453943
TI  - Supercharging a MnO2 Nanowire: An Amine-Altered Morphology Retains Capacity at
      High Rates and Mass Loadings.
AB  - The influence of hexamethylenetetraamine (HMTA) on the morphology of delta-MnO2
      and its properties for electrical energy storage are investigated-specifically
      for ultrathick delta-MnO2 layers in the micron scale. Planar arrays of gold@delta
      MnO2, core@shell nanowires, were prepared by electrodeposition with and without
      the HMTA and their electrochemical properties were evaluated. HMTA alters the
      MnO2 in three ways: First, it creates a more open morphology for the MnO2
      coating, characterized by "petals" with a thickness of 6 to 9 nm, rather than
      much thinner delta-MnO2 sheets seen in the absence of HMTA. Second, the
      electronic conductivity of the delta-MnO2 is increased by an order of magnitude.
      Third, delta-MnO2 prepared in HMTA shows a (001) interlayer spacing that is
      expanded by ~30% possibly accelerating Li transport. The net effect of "HTMA
      doping" is to dramatically improve high rate performance, culminating in an
      increase in the specific capacity for the thickest MnO2 shells examined here by a
      factor of 15 at 100 mV/s.

PMID- 28453944
TI  - Dietary intake and cardiometabolic biomarkers in relation to insulin resistance
      and hypertension in a middle-aged and elderly population in Beijing, China.
AB  - This study investigated the relationships of dietary intake and cardiometabolic
      biomarkers with insulin resistance and hypertension in rural middle-aged and
      elderly people in China. One hundred and eight middle-aged and elderly adults
      were recruited in Zhangfang village in May 2014. We measured blood pressure,
      anthropometric parameters, and biochemical indexes, including high-sensitivity C
      reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1),
      glucose, insulin, and blood lipids. Homeostasis model assessment of insulin
      resistance index (HOMA-IR) was assessed on the basis of fasting glucose and
      insulin. We recorded participant demographic characteristics, dietary intake, and
      lifestyle using questionnaires. Hypertensive participants had higher levels of
      triglycerides (TG), hsCRP, sICAM-1, body fat percentage (BF%), arm muscle
      circumference (AMC) and HOMA-IR than nonhypertensive individuals. Hypertensive
      participants had higher carbohydrate intake but lower intakes of protein and fat.
      Carbohydrate intake was positively correlated with hsCRP, sICAM-1, TG, BF%, and
      HOMA-IR, and was negatively correlated with AMC. Protein and fat intakes were
      negatively correlated with hsCRP and sICAM-1. Protein intake was also
      significantly negatively correlated with TG and HOMA-IR, and positively
      correlated with AMC. HOMA-IR was positively correlated with hsCRP, sICAM-1, TG
      and BF%, and negatively correlated with AMC. Multivariable linear regression
      indicated that TG, sICAM-1, and hsCRP were significantly associated with HOMA-IR.
      In conclusion, in a rural Chinese population, high intake of carbohydrate and low
      intake of fat and protein were associated with insulin resistance and
      hypertension, possibly by increasing inflammatory factors such as sICAM-1 and
      hsCRP, increasing BF% and increasing the level of plasma TG.

PMID- 28453945
TI  - An Approach to Reconciling Competing Ethical Principles in Aggregating
      Heterogeneous Health Preferences.
AB  - BACKGROUND: Health-related quality of life (HRQL) scores are used extensively to
      quantify the effectiveness of medical interventions. Societal preference-based
      HRQL scores aim to produce societal valuations of health by aggregating
      valuations from individuals in the general population, where each aggregation
      procedure embodies different ethical principles, as explained in social choice
      theory. METHODS: Using the Health Utilities Index as an exemplar, we evaluate
      societal preference-based HRQL measures in the social choice theory framework.
      RESULTS: We find that current preference aggregation procedures are typically
      justified in terms of social choice theory. However, by convention, they use only
      one of many possible aggregation procedures (the mean). Central to the choice of
      aggregation procedure is how to treat preference heterogeneity, which can affect
      analyses that rely on HRQL scores, such as cost-effectiveness analyses. We
      propose an analytical-deliberative framework for choosing one (or a set of)
      aggregation procedure(s) in a socially credible way, which we believe to be
      analytically sound and empirically tractable, but leave open the institutional
      mechanism needed to implement it. CONCLUSIONS: Socially acceptable decisions
      about aggregating heterogeneous preferences require eliciting stakeholders'
      preferences among the set of analytically sound procedures, representing
      different ethical principles. We describe a framework for eliciting such
      preferences for the creation of HRQL scores, informed by social choice theory and
      behavioral decision research.

PMID- 28453947
TI  - A Secondary Analysis of Mistreatment of Women During Childbirth in Health Care
      Facilities.
AB  - OBJECTIVE: To conduct a secondary qualitative analysis of a phenomenological
      study of traumatic childbirth to identify the types and frequency of mistreatment
      of women during childbirth in high-income countries. DESIGN: Analytic expansion
      was the type of secondary analysis chosen to make further use of a primary
      qualitative data set to ask a new question that was not included the original
      study aims. SETTING: The primary data set of women's experiences of traumatic
      childbirth was obtained via the Internet. PARTICIPANTS: The Internet sample of 40
      mothers consisted of 23 women from New Zealand, 8 from the United States, 6 from
      Australia, and 3 from the United Kingdom who experienced traumatic births.
      METHODS: Krippendorff's content analysis of categoric distinction was used to
      analyze the mothers' narratives of their traumatic births. The typology of
      mistreatment and abuse of women during childbirth in health care facilities
      worldwide outlined by Bohren et al. provided the categories for the content
      analysis. RESULTS: Six types of disrespectful and abusive treatment during
      childbirth were reported by participants, from those reported most often to least
      often: Failure to Meet Professional Standards of Care, Poor Rapport Between Women
      and Providers, Verbal Abuse, Physical Abuse, Health System
      Conditions/Constraints, and Stigma/Discrimination. CONCLUSION: Findings confirm
      results from studies of mistreatment of women during childbirth in health care
      facilities in low- and middle-income countries. Prevention and elimination of
      mistreatment of women during childbirth are the ethical responsibility of all
      obstetric health care providers.

PMID- 28453946
TI  - A Dermatologist's Approach to Genitourinary Syndrome of Menopause.
AB  - BACKGROUND: Genitourinary syndrome of menopause (GSM) is a debilitating condition
      caused by hypoestrogenism that presents with vaginal dryness and dyspareunia as
      well as other genital, sexual, and urinary symptoms. Previously known as atrophic
      vaginitis, the term GSM is now used. OBJECTIVE: To help familiarise
      dermatologists with diagnosing and managing GSM. METHODS: In total, 218 articles
      were identified and reviewed by 2 independent authors using PubMed. Articles
      included were from December 2005 to December 2015. Sixty-seven articles met our
      inclusion criteria. RESULTS: GSM is a clinical diagnosis, requiring the presence
      of symptoms that should be bothersome and not accounted for by another condition.
      A pH test may help with diagnosis as vaginal pH will be increased from acidic to
      neutral. The Papanicolaou test is not recommended because of poor clinical
      correlation. First-line treatment is low-dose local vaginal estrogen therapy,
      which has proven efficacy and safety. Serum estrogen levels are not significantly
      affected with the exception of creams containing high-dose conjugated equine
      estrogens. Other options have yet to be approved for use in Canada but show
      promise. CONCLUSION: GSM is a debilitating and common condition that suffers from
      barriers to diagnosis and treatment. Current treatments are well tolerated,
      rewarding, and effective with rapid onset.

PMID- 28453948
TI  - Depression and anxiety among chronic pain patients receiving prescription opioids
      and medical marijuana.
AB  - BACKGROUND: High rates of depression and anxiety have been consistently reported
      among patients suffering from chronic pain. Prescription opioids are one of the
      most common modalities for pharmacological treatment of pain, however in recent
      years medical marijuana(MM) has been increasingly used for pain control in the US
      and in several countries worldwide. The aim of this study was to compare levels
      of depression and anxiety among pain patients receiving prescription opioids and
      MM. METHODS: Participants were patients suffering from chronic pain treated with
      prescription opioids (OP,N=474), MM (N=329) or both (OPMM,N=77). Depression and
      anxiety were assessed using the depression module of the Patient Health
      Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7).
      RESULTS: Prevalence of depression among patients in the OP, MM and OPMM groups
      was 57.1%, 22.3% and 51.4%, respectively and rates of anxiety were 48.4%, 21.5%
      and 38.7%, respectively. After controlling for confounders, patients in the OP
      group were significantly more likely to screen positive for depression (Adjusted
      Odds Ratio(AOR)=6.18;95%CI=4.12-9.338) and anxiety(AOR=4.12;CI=3.84-5.71))
      compared to those in the MM group. Individuals in the OPMM group were more prone
      for depression (AOR for depression=3.34;CI=1.52-7.34)) compared to those in the
      MM group. LIMITATIONS: Cross-sectional study, restricting inference of causality.
      CONCLUSIONS: Levels of depression and anxiety are higher among chronic pain
      patients receiving prescription opioids compared to those receiving MM. Findings
      should be taken into consideration when deciding on the most appropriate
      treatment modality for chronic pain, particularly among those at risk for
      depression and anxiety.

PMID- 28453949
TI  - Replacing Heavily Damaged Teeth by Third Molar Autotransplantation With the Use
      of Cone-Beam Computed Tomography and Rapid Prototyping.
AB  - This article describes the autotransplantation of third molars to replace heavily
      damaged premolars and molars. Specifically, this article reports on the use of
      preoperative cone-beam computed tomographic planning and 3-dimensional (3D)
      printed replicas of donor teeth to prepare artificial tooth sockets. In the
      present case, an 18-year-old patient underwent autotransplantation of 3 third
      molars to replace 1 premolar and 2 molars that were heavily damaged after trauma.
      Approximately 1 year after the traumatic incident, autotransplantation with the
      help of 3D planning and rapid prototyping was performed. The right maxillary
      third molar replaced the right maxillary first premolar. The 2 mandibular wisdom
      teeth replaced the left mandibular first and second molars. During the surgical
      procedure, artificial tooth sockets were prepared with the help of 3D printed
      donor tooth copies to prevent iatrogenic damage to the actual donor teeth. These
      replicas of the donor teeth were designed based on the preoperative cone-beam
      computed tomogram and manufactured with the help of 3D printing techniques. The
      use of a replica of the donor tooth resulted in a predictable and straightforward
      procedure, with extra-alveolar times shorter than 2 minutes for all
      transplantations. The transplanted teeth were placed in infraocclusion and fixed
      with a suture splint. Postoperative follow-up showed physiologic integration of
      the transplanted teeth and a successful outcome for all transplants. In
      conclusion, this technique facilitates a straightforward and predictable
      procedure for autotransplantation of third molars. The use of printed analogues
      of the donor teeth decreases the risk of iatrogenic damage and the extra-alveolar
      time of the transplanted tooth is minimized. This facilitates a successful
      outcome.

PMID- 28453950
TI  - Histological Assessment of the Carotid Sheath in Patients With Oral Squamous Cell
      Carcinoma.
AB  - PURPOSE: During surgical management of the neck using various types of neck
      dissection, the carotid sheath is removed, in particular, the part adjacent to
      the jugular lymph node chain, with the intention of preventing recurrence from
      the lymphatics present within it. The role of the carotid sheath as a potential
      origin for nodal recurrence has not been proved thus far. Working in a tissue
      plane between the carotid sheath and the neurovascular structures of the neck can
      lead to a greater chance of damage to these structures. Also, the carotid sheath
      is a strong fibroelastic tissue barrier that shields the internal jugular vein
      and carotid artery from saliva and local infection during the postoperative
      period. Thus, this study investigated the histopathology of the carotid sheath in
      patients with oral squamous cell carcinoma (OSCC) and assessed the pathologic
      infiltration of the carotid sheath when grossly uninvolved. PATIENTS AND METHODS:
      Pathologic infiltration and histopathologic characteristics of the entire length
      of the carotid sheath were assessed in 30 biopsy-proved cases of OSCC; these
      patients underwent surgical excision of the lesion in addition to neck dissection
      from 2013 to 2015 in the craniofacial unit of the authors' institution. RESULTS:
      The carotid sheath consisted of fibrofatty tissue and interspersed nerve bundles.
      Neutrophilic infiltration and dilated lymphatic channels were seen in all 30
      cases. Miniature lymph nodes adherent to the carotid sheath were seen in 5 cases
      and some lymphoid aggregates were seen in 15 cases. The carotid sheath in all 30
      cases (metastatic and nonmetastatic) was free from tumor deposit and lymphatic
      tumor emboli, which are indicators of tumor cell infiltration. CONCLUSION:
      Indicators of tumor cell infiltration were not found in any of the 30 cases. The
      result did not vary with the age or gender of the patient, tumor size, location,
      staging or grading of the tumor, or even when there were metastatic lymph nodes
      in the gross specimen. Hence, the role of the carotid sheath as a potential
      origin for nodal recurrence is questionable and its removal needs
      reconsideration.

PMID- 28453951
TI  - Are Biodegradable Plates Applicable in Endoscope-Assisted Open Reduction and
      Internal Fixation of Mandibular Subcondyle Fractures?
AB  - PURPOSE: To investigate whether biodegradable plates are applicable in endoscope
      assisted open reduction and internal fixation (EAORIF) of mandibular subcondyle
      fractures. MATERIALS AND METHODS: This retrospective case-series study included
      patients with mandibular subcondyle fractures treated with EAORIF using an
      unsintered hydroxyapatite particles/poly-l-lactide biodegradable plate system,
      with at least 6 months of clinical follow-up data available. The outcome
      variables were fracture healing with postoperative stability and postoperative
      complications. Other variables included age, gender, fracture site, cause of
      injury, accompanying mandibular fracture, total follow-up period, fracture
      classification, extent of displacement, preoperative status of occlusion,
      preoperative mandibular movements, fixation materials in accompanying mandibular
      fracture, location and number of fixation plates, periods of intermaxillary
      fixation/elastic bands, and postoperative mandibular movements. Fracture healing
      in these patients was assessed by comparing the immediate postoperative cone-beam
      computed tomography (CBCT) images with those obtained at least 3 months after
      surgery. RESULTS: A total of 11 patients, 9 male and 2 female, with a mean +/-
      standard deviation age of 35.3 +/- 15.9 years, were included. The mean follow-up
      period was 18.8 +/- 7.8 months. Four patients had an accompanying mandibular
      fracture. Two 4-hole, 2.0-mm biodegradable plates were fixed with 6-mm screws
      along the posterior border of the mandibular ramus and near the sigmoid notch.
      Complete bone formation around the fracture lines or fading of the fracture
      lines, with no change in the position of the fractured segments, was observed on
      the postoperative CBCT images at 3 months. With the exception of 2 patients, no
      patient complained of plate palpability, deviation in occlusion, or discomfort
      during the postoperative follow-up period. CONCLUSIONS: EAORIF using
      biodegradable plates for mandible subcondylar fractures is a stable and reliable
      method, with considerable advantages compared with titanium plates.

PMID- 28453952
TI  - Where is the locus of the lowercase advantage during sentence reading?
AB  - While most models of visual word identification and reading posit that a word's
      visual codes are rapidly transformed onto case-invariant representations (i.e.,
      table and TABLE would equally activate the word unit corresponding to "table"), a
      number of experiments have shown a lowercase advantage in various word
      identification and reading tasks. In the present experiment, we examined the
      locus of this lowercase advantage by comparing the pattern of eye movements when
      reading sentences in lowercase vs. uppercase. Each sentence contained a target
      word that was high or low in word-frequency. Overall, results showed faster
      reading times for lowercase than for uppercase sentences. More important, while
      the word-frequency effect was sizeable in the first-fixation durations on the
      target word, the lowercase advantage only arose in the gaze durations (i.e., the
      sum of durations of first-pass fixations on the target word, including
      refixations). Furthermore, we found an effect of word-frequency, but not of
      letter case, in the first-fixation duration on target words with multiple first
      pass fixations. Taken together, these findings suggest that the lowercase
      advantage reflects operations that do not occur in the initial contact with the
      lexical entries.

PMID- 28453953
TI  - Dual-functioning peptides discovered by phage display increase the magnitude and
      specificity of BMSC attachment to mineralized biomaterials.
AB  - Design of biomaterials for cell-based therapies requires presentation of specific
      physical and chemical cues to cells, analogous to cues provided by native
      extracellular matrices (ECM). We previously identified a peptide sequence with
      high affinity towards apatite (VTKHLNQISQSY, VTK) using phage display. The aims
      of this study were to identify a human MSC-specific peptide sequence through
      phage display, combine it with the apatite-specific sequence, and verify the
      specificity of the combined dual-functioning peptide to both apatite and human
      bone marrow stromal cells. In this study, a combinatorial phage display
      identified the cell binding sequence (DPIYALSWSGMA, DPI) which was combined with
      the mineral binding sequence to generate the dual peptide DPI-VTK. DPI-VTK
      demonstrated significantly greater binding affinity (1/KD) to apatite surfaces
      compared to VTK, phosphorylated VTK (VTKphos), DPI-VTKphos, RGD-VTK, and peptide
      free apatite surfaces (p < 0.01), while significantly increasing hBMSC adhesion
      strength (tau50, p < 0.01). MSCs demonstrated significantly greater adhesion
      strength to DPI-VTK compared to other cell types, while attachment of MC3T3 pre
      osteoblasts and murine fibroblasts was limited (p < 0.01). MSCs on DPI-VTK coated
      surfaces also demonstrated increased spreading compared to pre-osteoblasts and
      fibroblasts. MSCs cultured on DPI-VTK coated apatite films exhibited
      significantly greater proliferation compared to controls (p < 0.001). Moreover,
      early and late stage osteogenic differentiation markers were elevated on DPI-VTK
      coated apatite films compared to controls. Taken together, phage display can
      identify non-obvious cell and material specific peptides to increase human MSC
      adhesion strength to specific biomaterial surfaces and subsequently increase cell
      proliferation and differentiation. These new peptides expand biomaterial design
      methodology for cell-based regeneration of bone defects. This strategy of
      combining cell and material binding phage display derived peptides is broadly
      applicable to a variety of systems requiring targeted adhesion of specific cell
      populations, and may be generalized to the engineering of any adhesion surface.

PMID- 28453954
TI  - Local delivery of chondroitinase ABC with or without stromal cell-derived factor
      1alpha promotes functional repair in the injured rat spinal cord.
AB  - Traumatic spinal cord injury (SCI) is a devastating event for which functional
      recovery remains elusive. Due to the complex nature of SCI pathology, a
      combination treatment strategy will likely be required for success. We
      hypothesized that tissue and functional repair would be achieved in a rat model
      of impact-compression SCI by combining degradation of the glial scar, using
      chondroitinase ABC (ChABC), with recruitment of endogenous neural precursor cells
      (NPCs), using stromal cell-derived factor 1alpha (SDF). To test this hypothesis,
      we designed a crosslinked methylcellulose hydrogel (XMC) for minimally invasive,
      localized, and sustained intrathecal drug delivery. ChABC was released from XMC
      using protein-peptide affinity interactions while SDF was delivered by
      electrostatic affinity interactions from polymeric nanoparticles embedded in XMC.
      Rats with SCI were treated acutely with a combination of SDF and ChABC, SDF
      alone, ChABC alone, or vehicle alone, and compared to injury only. Treatment with
      ChABC, both alone and in combination with SDF, resulted in faster and more
      sustained behavioural improvement over time than other groups. The significantly
      reduced chondroitin sulfate proteoglycan levels and greater distribution of NPCs
      throughout the spinal cord tissue with ChABC delivery, both alone and in
      combination with SDF, may explain the improved locomotor function. Treatment with
      SDF alone had no apparent effect on NPC number or distribution nor synergistic
      effect with ChABC delivery. Thus, in this model of SCI, tissue and functional
      repair is attributed to ChABC.

PMID- 28453955
TI  - Acoustic tweezing cytometry enhances osteogenesis of human mesenchymal stem cells
      through cytoskeletal contractility and YAP activation.
AB  - Human mesenchymal stem cells (hMSCs) have great potential for cell-based
      therapies for treating degenerative bone diseases. It is known that mechanical
      cues in the cell microenvironment play an important role in regulating osteogenic
      (bone) differentiation of hMSCs. However, mechanoregulation of lineage commitment
      of hMSCs in conventional two-dimensional (2D) monocultures or bioengineered three
      dimensional (3D) tissue constructs remains suboptimal due to complex biomaterial
      design criteria for hMSC culture. In this study, we demonstrate the feasibility
      of a novel cell mechanics and mechanobiology tool, acoustic tweezing cytometry
      (ATC), for mechanical stimulation of hMSCs. ATC utilizes ultrasound (US) pulses
      to actuate functionalized lipid microbubbles (MBs) which are covalently attached
      to hMSCs via integrin binding to exert forces to the cells. ATC stimulation
      increases cytoskeletal contractility of hMSCs regardless of the cell area.
      Furthermore, ATC application rescues osteogenic differentiation of hMSCs in
      culture conditions that are intrinsically repressive for hMSC osteogenesis (e.g.,
      soft cell culture surfaces). ATC application activates transcriptional regulator
      YAP to enhance hMSC osteogenesis. Our data further show that F-actin, myosin II,
      and RhoA/ROCK signaling functions upstream of YAP activity in mediating ATC
      stimulated hMSC osteogenesis. With the capability of applying controlled dynamic
      mechanical stimuli to cells, ATC provides a powerful tool for mechanoregulation
      of stem cell behaviors in tissue engineering and regenerative medicine
      applications.

PMID- 28453956
TI  - Molecular imaging of activated platelets via antibody-targeted ultra-small iron
      oxide nanoparticles displaying unique dual MRI contrast.
AB  - Magnetic resonance imaging (MRI) is a powerful and indispensable tool in medical
      research, clinical diagnosis, and patient care due to its high spatial resolution
      and non-limited penetration depth. The simultaneous use of positive and negative
      MRI imaging that employs the same contrast agents will significantly improve
      detection accuracy. Here we report the development of functional multimodal iron
      oxide nanoparticles for targeted MRI of atherothrombosis using a combination of
      chemical and biological conjugation techniques. Monodisperse, water-soluble and
      biocompatible ultra-small magnetic dual contrast iron oxide nanoparticles
      (DCIONs) were generated using a high-temperature co-precipitation route and
      appeared to be efficient positive and negative dual contrast agents for magnetic
      resonance imaging. Using a unique chemo-enzymatic approach involving copper-free
      click chemistry and Staphylococcus aureus sortase A enzyme conjugation, DCIONs
      were functionalized with single-chain antibodies (scFv) directed against
      activated platelets for targeting purposes. The DCIONs were also labelled with
      fluorescent molecules to allow for optical imaging. The antigen binding activity
      of the scFv was retained and resulted in the successful targeting of contrast
      agents to thrombosis as demonstrated in a range of in vitro and in vivo
      experiments. T1- and T2-weighted MRI of thrombi was recorded and demonstrated the
      great potential of dual T1/T2 contrast iron oxide particles in imaging of
      cardiovascular disease.

PMID- 28453957
TI  - A magnetic droplet vaporization approach using perfluorohexane-encapsulated
      magnetic mesoporous particles for ultrasound imaging and tumor ablation.
AB  - Phase change agents consisting of low boiling point perfluorocarbon (PFC)
      compounds have attracted increasing attention for ultrasound contrast-enhanced
      imaging and tumor therapy. However, the refraction, acoustic shadowing,
      reverberation, or limited penetration depth hamper their practical applications
      through previously reported acoustic droplet vaporization (ADV) or optical
      droplet vaporization (ODV) technique. Herein, we demonstrate a magnetic droplet
      vaporization (MDV) approach by loading perflurohexane (PFH) in magnetic
      mesoporous particles with a hollow space to carry out ultrasound imaging and
      tumor ablation. In vitro and in vivo magnetic thermal effects show that magnetic
      energy can be efficiently transformed into thermal energy by the PFH-encapsulated
      magnetic mesoporous particles, and then leading to vaporization of the loaded
      PFH. Owing to the generation of the PFH gas bubbles, the ultrasound signals are
      greatly improved in both harmonic mode and B mode. Simultaneously, anti-cancer
      experiments demonstrate that the tumor can be ablated after treating with the MDV
      method for 4 days, demonstrating highly efficient anti-cancer effects.

PMID- 28453958
TI  - The novel technique of post-hysterectomy vaginal vault prolapse repair: Apical
      sling and "neocervix" formation.
AB  - OBJECTIVE: We primarily aimed to evaluate the effectiveness of the novel
      technique: bilateral sacrospinous fixation by monofilament polypropylene apical
      sling combined with "neocervix" formation in surgical treatment of post -
      hysterectomy vaginal vault prolapse. The secondary objective was to estimate the
      impact of the surgery on voiding function and quality of life. STUDY DESIGN: This
      prospective study involved 61 women suffering from post-hysterectomy prolapse. We
      used the following criteria to evaluate the results of surgical treatment:
      results of vaginal examination (POP-Q system), uroflowmetry, bladder ultrasound,
      validated questionnaires were used. All listed parameters were determined before
      the surgery and at control examinations in 1, 6, 12 months after the treatment.
      RESULTS: Mean operation time was 35min. No cases of intraoperative damage to the
      bladder/rectum, as well as clinically significant bleeding were noted.At 12-month
      follow-up anatomical cure rate (<=stage I, POP-Q) was 100%, 94,4% and 100% for
      vaginal apex, anterior and posterior vaginal walls, respectively. The following
      long-term complications were noted stress urinary incontinence de novo and
      urgency de novo were noted in 6.5% and 4,9%, respectively. Statistically
      significant (P<0.05) improvement in peak flow rate was observed according to
      uroflowmetry. Comparison of the scores by the questionnaires revealed a
      significant improvement in the quality of life in the postoperative period.
      CONCLUSION: The novel technique: combination of the apical sling and purse-string
      "neocervix" formation appears to be effective and safe method for treatment
      patients with vaginal vault prolapse. The technique improves voiding function and
      quality of life.

PMID- 28453960
TI  - Implication of a novel Gla-containing protein, Gas6 in the pathogenesis of
      insulin resistance, impaired glucose homeostasis, and inflammation: A review.
AB  - Growth arrest specific 6 (Gas6), a vitamin K-dependent protein plays a
      significant role in the regulation of cellular homeostasis via binding with TAM
      receptor tyrosine kinases. Several studies reported the role of Gas6 in cancer,
      glomerular injury, obesity, and inflammation, however, very little is known about
      its role in insulin resistance (IR) and impaired glucose metabolism. Majority of
      the studies reported an inverse correlation of Gas6 protein levels or gene
      polymorphism with plasma glucose, HbA1c, IR, and inflammatory cytokines among
      type 2 diabetes (T2D) and obese subjects. However, few studies reported a
      positive correlation of Gas6 protein levels or gene polymorphism with IR and
      inflammation among obese subjects. This review for the first time provides an
      overview of the association of Gas6 protein levels or gene polymorphism with IR,
      glucose intolerance, and inflammation among T2D and obese subjects. This review
      also depicts the probable mechanism underlying the association of Gas6 with
      glucose intolerance and inflammation. The outcome of this review will increase
      the understanding about the role of Gas6 in the pathogenesis of IR, glucose
      intolerance and inflammation and that should in turn lead to the design of
      clinical interventions to improve glucose metabolism and the lives of the T2D
      patients.

PMID- 28453959
TI  - Uroflowmetric changes, success rate and complications following Tension-free
      Vaginal Tape Obturator (TVT-O) operation in obese females.
AB  - OBJECTIVE: The goal of this study was to evaluate the outcome of Tension-free
      Vaginal Tape Obturator (TVT-O) operation in the treatment of urodynamic stress
      incontinence (USI) in obese females, with respect to uroflowmetric changes,
      success rate and postoperative complications. METHODS: This prospective
      observational study included 26 patients with USI at the Obstetrics & Gynecology
      department-Cairo University hospital during the year 2015. The participants had
      body mass index (BMI)>=30. Patients underwent TVT-O operation. Follow up of the
      patients was performed by cough test and uroflowmetry after one week, one month,
      three months and six months. Postoperative complications such as groin pain,
      sense of incomplete emptying, need to strain to complete micturition and urinary
      tract infection were recorded. Comparisons between groups were done using Chi
      square, Phi-Cramer test for categorical variables. RESULTS: The mean age for the
      subjects was 43.58+/-9.01years. The mean BMI was 33.4+/-2.1. The success rate of
      TVT-O operation was 21 out of 26 patients (~81%). Normal maximum flow rate was in
      88% of patients at week one and was normal in 100% of patients at months three
      and six (p=0.101 & 0.101). Postoperative groin pain was the main complaint during
      the first week after operation and decreased significantly from week one to the
      1st month postoperative (84.62% & 65.38%, P=0.041). CONCLUSION: TVT-O operation
      showed a high success rate in treatment of USI in obese patients without
      affecting the voiding function of the bladder as proven by the uroflowmetry. The
      main postoperative complaint was the groin pain which significantly improved
      after one month.

PMID- 28453961
TI  - Diabetic nephropathy: New insights into established therapeutic paradigms and
      novel molecular targets.
AB  - Diabetic nephropathy is one of the most prevalent microvascular complication in
      patients suffering from diabetes and is reported to be the major cause of renal
      failure when compared to any other kidney disease. Currently, available therapies
      provide only symptomatic relief and unable to treat the underlying
      pathophysiology of diabetic nephropathy. This review will explore new insights
      into the established therapeutic paradigms targeting oxidative stress,
      inflammation and endoplasmic reticulum stress with the focus on recent clinical
      developments. Apart from this, the involvement of novel cellular and molecular
      mechanisms including the role of endothelin-receptor antagonists, Wnt signaling
      pathway, epigenetics and micro RNA is also discussed so that key molecular
      switches involved in the pathogenesis of diabetic nephropathy can be identified.
      Elucidating new molecular pathways will help in the development of novel
      therapeutics for the prevention and treatment of diabetic nephropathy.

PMID- 28453962
TI  - A bead-based immunofluorescence-assay on a microfluidic dielectrophoresis
      platform for rapid dengue virus detection.
AB  - The proof of concept of utilizing a microfluidic dielectrophoresis (DEP) chip was
      conducted to rapidly detect a dengue virus (DENV) in vitro based on the
      fluorescence immunosensing. The mechanism of detection was that the DEP force was
      employed to capture the modified beads (mouse anti-flavivirus monoclonal antibody
      coated beads) in the microfluidic chip and the DENV modified with fluorescence
      label, as the detection target, can be then captured on the modified beads by
      immunoreaction. The fluorescent signal was then obtained through fluorescence
      microscopy, and then quantified by ImageJ freeware. The platform can accelerate
      an immuno-reaction time, in which the on-chip detection time was 5min, and
      demonstrating an ability for DENV detection as low as 104 PFU/mL. Furthermore,
      the required volume of DENV samples dramatically reduced, from the commonly used
      ~50uL to ~15uL, and the chip was reusable (>50x). Overall, this platform provides
      a rapid detection (5min) of the DENV with a low sample volume, compared to
      conventional methods. This proof of concept with regard to a microfluidic
      dielectrophoresis chip thus shows the potential of immunofluorescence based-assay
      applications to meet diagnostic needs.

PMID- 28453963
TI  - Rare earth elements and their release dynamics under pre-definite redox
      conditions in a floodplain soil.
AB  - For the first time, the impact of pre-definite redox conditions on the release
      dynamics of rare earth elements (REEs) and the determining factors pH, iron (Fe),
      manganese (Mn), aluminum (Al), dissolved organic carbon (DOC), dissolved
      inorganic carbon (DIC), and sulfate (SO42-) in a floodplain soil was elucidated
      using an advanced, highly sophisticated automatic biogeochemical microcosm
      apparatus. The redox potential (EH) ranged between +82 and + 498 mV during the
      experiment. The systematic increase of EH caused a decreasing pH from 6.6 to 4.6
      which resulted in an enhanced mobilization and release of REEs along with Fe, Al,
      and Mn under oxic and acidic conditions. Also, organic matter seems to contribute
      to the mobilization of REEs under changing redox conditions. A factor analysis
      identified that the REEs form one group with EH, Fe, Al, and Mn what indicates
      that REEs and sesquioxides have a similar geochemical behavior. The pH, DOC, and
      DIC are together in another cluster which demonstrates that their behavior
      substantially differs from the other group. The sequential extraction procedure
      revealed that the majority of the REEs were bound in the residual fraction,
      followed by the reducible, the oxidisable and the water
      soluble/exchangeable/carbonate bound fraction. Future studies should further
      elucidate the specific release kinetics of REEs, the controlling factors on the
      release dynamics and the underlying mobilization processes in highly dynamic
      wetland soils around the globe.

PMID- 28453964
TI  - Degradation of sulfadimethoxine catalyzed by laccase with soybean meal extract as
      natural mediator: Mechanism and reaction pathway.
AB  - Natural laccase-mediator systems have been well recognized as an eco-friendly and
      energy-saving approach in environmental remediation, whose further application is
      however limited by the high cost of natural mediators and relatively long
      treatment time span. This study evaluated the water extract of soybean meal, a
      low-cost compound system, in mediating the laccase catalyzed degradation of a
      model contaminant of emerging concern, sulfadimethoxine (SDM), and demonstrated
      it as a promising alternative mediator for soil and water remediation. Removal of
      73.3% and 65.6% was achieved in 9 h using soybean meal extract (SBE) as the
      mediating system for laccase-catalyzed degradation of sulfadimethoxine at the
      concentration of 1 ppm and 10 ppm, respectively. Further degradation of
      sulfadimethoxine was observed with multiple SBE additions. Using SBE as mediator
      increased the 9-h removal of SDM at 1 ppm initial concentration by 52.9%, 49.4%,
      and 36.3% in comparison to the system mediated by 1-Hydroxybenzotriazole (HBT), p
      Coumaric acid (COU) and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) (ABTS),
      respectively. With the detection of stable coupling products formed with radical
      scavenger (5,5-Dimethyl-1-pyrroline N-oxide, DMPO), three phenolic compounds
      (vanillin, apocynin, and daidzein) in SBE were confirmed to serve as mediators
      for Trametes versicolor laccase. Reaction pathways were proposed based on the
      results of High Resolution Mass Spectrometry. SO2 excursion happened during SDM
      transformation, leading to elimination of antimicrobial activity. Therefore, as a
      natural, phenol rich, and affordable compound system, the future application of
      SBE in wastewater and soil remediation is worth exploring.

PMID- 28453965
TI  - Adsorption behavior and mechanism of different arsenic species on mesoporous
      MnFe2O4 magnetic nanoparticles.
AB  - Arsenic pollution poses severe threat to human health, therefore dealing with the
      problem of arsenic contamination in water bodies is extremely important. The
      adsorption behaviors of different arsenic species, such as arsenate (As(V)), p
      arsanilic acid (p-ASA), roxarsone (ROX), dimethylarsenate (DMA) from water using
      mesoporous bimetal oxide magnetic manganese ferrite nanoparticles (MnFe2O4) have
      been detailedly investigated. The adsorbent was synthesized via a facile co
      precipitation approach and recovered conveniently owing to its strong magnetic
      properties. The obtained MnFe2O4 with large surface area and abundant hydroxyly
      functional groups exhibited excellent adsorption performance for As(V) and p-ASA,
      in contrast to ROX and DMA with the maximum adsorption capacities of As(V), p
      ASA, ROX and DMA of 68.25 mg g-1, 59.45 mg g-1, 51.49 mg g-1, and 35.77 mg g-1,
      respectively. The Langmuir model and the pseudo-second-order kinetic model
      correlated satisfactorily with the adsorption thermodynamics and kinetics, and
      thermodynamic parameters depicted the spontaneous endothermic nature for the
      adsorption of different arsenic species. The adsorption mechanism of different
      arsenic species onto MnFe2O4 nanoparticles at various pH values could be
      explained by surface complexation and molecular structural variations. Attenuated
      Total internal Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and
      X-ray photoelectron spectroscopy (XPS) further proved that arsenic species were
      bonded to the surface of MnFe2O4 through the formation of an inner-sphere complex
      between the arsenic acid moiety and surface metal centers. The results would help
      to know the interaction of arsenic species with iron-manganese minerals and the
      mobility of arsenic species in natural environments.

PMID- 28453966
TI  - Psychotherapy for depression among advanced, incurable cancer patients: A
      systematic review and meta-analysis.
AB  - BACKGROUND: There is a high prevalence of depressive disorder and depressive
      symptoms among advanced, incurable cancer patients. Patients commonly report a
      preference for non-pharmacological treatments such as psychotherapy over
      pharmacological treatments for depression. The objective of this review was to
      investigate the effectiveness of psychotherapy for the treatment of depression in
      people with advanced, incurable cancer via a meta-analysis of randomized
      controlled trials (RCTs). METHODS: We searched research databases and clinical
      trial registries for studies published prior to June 2015. No language
      restrictions were applied when selecting studies. Cochrane Collaboration meta
      analysis review methodology was used. All relevant RCTs comparing psychotherapy
      with control conditions on depression outcomes for adults with advanced cancer
      were eligible for inclusion. We calculated pooled effect sizes using Hedges g and
      a standardized mean difference (SMD) of change between baseline and post
      treatment scores. Quality of evidence was rated using the Grading of
      Recommendations, Assessment, Development and Evaluation (GRADE) approach.
      RESULTS: Of 13 studies included in the review, 12 reported data suitable for meta
      analysis. Psychotherapy was associated with moderate decrease in depression score
      (SMD -0.67, 95% confidence interval -1.06 to -0.29, P=0.0005). Few studies
      focused on people with clinically diagnosed depression. Overall, quality of
      evidence across the included studies was rated as low, and heterogeneity was
      high. CONCLUSIONS: Low quality evidence suggests that psychotherapy is moderately
      more effective for the amelioration of symptoms of depression among advanced,
      incurable cancer patients than the control conditions. There is insufficient high
      quality evidence supporting the effectiveness of psychotherapy for patients with
      clinically diagnosed depression.

PMID- 28453967
TI  - Therapeutic vaccination for chronic hepatitis B.
AB  - A therapeutic vaccine is meant to activate the patient's immune system to fight
      and finally control or ideally eliminate an already established infectious
      pathogen. Whereas the success of prophylactic vaccination is based on rapid
      antibody-mediated neutralization of an invading pathogen, control and elimination
      of persistent viruses such as hepatitis, herpes or papilloma viruses requires
      multi-specific and polyfunctional effector T cell responses. These are ideally
      directed against continuously expressed viral antigens to keep the pathogen in
      check. Activation of a humoral immune response in order to lower viral antigen
      load and to limit virus spread, however, confers an additional benefit.
      Therapeutic vaccines are under development for a number of chronic infections and
      require an intelligent vaccine design. Hepatitis B virus (HBV) infection may
      serve as a prime example since a spontaneous, immune-mediated recovery of chronic
      hepatitis B and an elimination of the virus is possible even if it is observed
      only in very rare cases. In this review, we summarize the current knowledge and
      potential improvements of therapeutic vaccines for chronic hepatitis B.

PMID- 28453968
TI  - Association of altered collagen content and lysyl oxidase expression in
      degenerative mitral valve disease.
AB  - BACKGROUND: Collagen cross-linking is mediated by lysyl oxidase (LOX) enzyme in
      the extracellular matrix (ECM) of mitral valve leaflets. Alterations in collagen
      content and LOX protein expression in the ECM of degenerative mitral valve may
      enhance leaflet expansion and disease severity. METHODS: Twenty posterior
      degenerative mitral valve leaflets from patients with severe mitral regurgitation
      were obtained at surgery. Five normal posterior mitral valve leaflets procured
      during autopsy served as controls. Valvular interstitial cells (VICs) density was
      quantified by immunohistochemistry, collagen Types I and III by picro-sirius red
      staining and immunohistochemistry, and proteoglycans by alcian blue staining.
      Protein expression of LOX and its mediator TGFbeta1 were quantified by
      immunofluorescence and gene expression by PCR. RESULTS: VIC density was
      increased, structural Type I collagen density was reduced, while reparative Type
      III collagen and proteoglycan densities were increased (P<.0001) with an increase
      in spongiosa layer thickness in myxomatous valves. These changes were associated
      with a reduction in LOX (P<.0001) and increase in TGFbeta1 protein expression
      (P<.0001). However, no significant change was seen in gene expression. Linear
      regression analysis identified a correlation between Type I collagen density and
      LOX grade (R2=0.855; P<.0001). CONCLUSIONS: Reduced Type I collagen density with
      a simultaneous increase in Type III collagen and proteoglycan densities possibly
      contributes to spongiosa layer expansion resulting in incompetent mitral valve
      leaflets. Observed changes in Type I and III collagen densities in Degenerative
      Mitral Valve Disease may be secondary to alterations in LOX protein expression,
      contributing to disorganization of ECM and disease severity.

PMID- 28453970
TI  - On-chip ultrasonic manipulation of microparticles by using the flexural vibration
      of a glass substrate.
AB  - As biotechnology develops, techniques for manipulating and separating small
      particles such as cells and DNA are required in the life sciences. This paper
      investigates on-chip manipulation of microparticles in small channels by using
      ultrasonic vibration. The chip consists of a rectangular glass substrate with a
      cross-shaped channel (cross-section: 2.0*2.0mm2) and four lead zirconate titanate
      transducers attached to the substrate's four corners. To efficiently generate the
      flexural vibration mode on the chip, we used finite element analysis to optimize
      the configurations of the glass substrate and transducers. Silicon carbide
      microparticles with an average diameter of 50MUm were immersed in the channels,
      which were filled with ethanol. By applying an in-phase input voltage of 75V at
      225kHz to the four transducers, a flexural vibration mode with a wavelength of
      13mm was excited on the glass substrate, and this flexural vibration generated an
      acoustic standing wave in the channel. The particles could be trapped at the
      nodal lines of the standing wave. By controlling the driving phase difference
      between the two pairs of transducers, the vibrational distribution of the
      substrate could be moved along the channels so that the acoustic standing wave
      moved in the same direction. The trapped particles could be manipulated by the
      two-phase drive, and the transport direction could be switched at the junction of
      the channels orthogonally by changing the combination of the driving condition to
      four transducers.

PMID- 28453969
TI  - Reducing intrusive traumatic memories after emergency caesarean section: A proof
      of-principle randomized controlled study.
AB  - : Preventative psychological interventions to aid women after traumatic
      childbirth are needed. This proof-of-principle randomized controlled study
      evaluated whether the number of intrusive traumatic memories mothers experience
      after emergency caesarean section (ECS) could be reduced by a brief cognitive
      intervention. 56 women after ECS were randomized to one of two parallel groups in
      a 1:1 ratio: intervention (usual care plus cognitive task procedure) or control
      (usual care). The intervention group engaged in a visuospatial task (computer
      game 'Tetris' via a handheld gaming device) for 15 min within six hours following
      their ECS. The primary outcome was the number of intrusive traumatic memories
      related to the ECS recorded in a diary for the week post-ECS. As predicted,
      compared with controls, the intervention group reported fewer intrusive traumatic
      memories (M = 4.77, SD = 10.71 vs. M = 9.22, SD = 10.69, d = 0.647 [95% CI:
      0.106, 1.182]) over 1 week (intention-to-treat analyses, primary outcome). There
      was a trend towards reduced acute stress re-experiencing symptoms (d = 0.503 [95%
      CI: -0.032, 1.033]) after 1 week (intention-to-treat analyses). Times series
      analysis on daily intrusions data confirmed the predicted difference between
      groups. 72% of women rated the intervention "rather" to "extremely" acceptable.
      This represents a first step in the development of an early (and potentially
      universal) intervention to prevent postnatal posttraumatic stress symptoms that
      may benefit both mother and child. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.gov, NCT02502513.

PMID- 28453971
TI  - Segmented filamentous bacteria, Th17 inducers and helpers in a hostile world.
AB  - The Th17 cell composition in the murine gut is strikingly dependent on the
      presence of the commensal segmented filamentous bacteria (SFB). SFB potently
      stimulates innate and adaptive immune responses and protects the host from
      pathogens both in and outside of the gut, partly due to its unique ability to
      promote a Th17-fostering environment. Recent work has highlighted the role of the
      tight adherence of SFB to the intestinal surface in mediating the potent
      immunostimulatory potential of SFB. Progress has also been made in our
      understanding of how SFB fosters this protective immune environment on the
      cellular and molecular level. This review focuses on the ability of SFB to
      specifically stimulate Th17 immunity.

PMID- 28453972
TI  - Exposure to ambient PM2.5 associated with overall and domain-specific disability
      among adults in six low- and middle-income countries.
AB  - BACKGROUND: Exposure to particulate matter pollution is associated with various
      cardiopulmonary diseases, which are closely related with disability. The direct
      relationship between air pollution and disability, however, has not been fully
      explored. METHODS: We used data from 45,625 participants in the Study on global
      AGEing and adult health in six low- and middle-income countries. The 12-item
      version of the World Health Organization Disability Assessment Schedule (WHODAS
      2.0) was used to measure the disability with six domains (cognition, mobility,
      self-care, getting along, life activities, and participation in society).
      Participants' community addresses were used to estimate annual concentration of
      PM2.5 using satellite data. We used linear mixed models to examine the effects of
      PM2.5 on overall and domain-specific WHODAS scores. RESULTS: Exposure to PM2.5
      was significantly associated with greater disability score (a higher score
      implies a greater disability); each 10MUg/m3 increase corresponded to 0.72 (95%
      CI: 0.22, 1.22) increase in overall disability score. Compared with low PM2.5
      level (<14.33MUg/m3), moderate (14.33-27.83MUg/m3) and high exposure levels
      (>27.83MUg/m3) were associated with 3.43 (95% CI: 1.43, 5.43) and 3.72 (95% CI:
      1.59, 5.86) increase in disability scores. Among the six domains, cognition,
      mobility and getting along were found to be associated with PM2.5. Stratified
      analyses found that women and older subjects were more sensitive to this effect.
      CONCLUSION: Exposure to ambient PM2.5 might be one risk factor of disability in
      the low- and middle-income countries, women and older adults are the vulnerable
      population; and among the six domains, cognition, mobility and getting along are
      more relevant to this effect.

PMID- 28453973
TI  - Determinants of children's exposure to pyrethroid insecticides in western France.
AB  - Pyrethroids are insecticides frequently used in agriculture and in the home;
      exposure occurs through dietary and non-dietary pathways, including indoor and
      outdoor environmental contamination. Our objective was to study the potential
      determinants of pyrethroid metabolite concentrations measured in children's urine
      samples and in the dust of their homes. Specifically, we measured urinary
      metabolites from morning spot samples of 245 six-year-old children living in
      Brittany (France) in 2009-2012 and from dust vacuumed from the floor of their
      homes. Mothers reported home insecticide use, dietary habits, sociodemographic
      data; residential and school proximity to agricultural crops was assessed with
      spatialized data. The metabolites cis-DBCA, trans-DCCA, cis-DCCA, 3-PBA, and F
      PBA were detected in 84, 95, 64, 63, and 16% of the urine samples, respectively.
      Permethrin, cypermethrin, cyfluthrin, deltamethrin, and tetramethrin pyrethroids
      were detected in 100, 56, 9, 15, and 26% of the dust samples, respectively.
      Multiple regression analysis suggested diet plays a role in children's exposure,
      in particular, the food groups "pasta, rice or semolina" (for cis-DCCA and F
      PBA), fruit (3-PBA), "breakfast cereals and whole grain bread" (cis-DBCA), and
      the global proportion of organic food in diet (for cis-DBCA, trans-DCCA).
      Children with a parent occupationally exposed to pesticides were about 3-times
      more likely to have higher urinary concentrations of 3-PBA (OR=2.8, 95% CI [1.2;
      6.5]). Dust content was correlated mainly with household insecticide use: higher
      mean concentrations of permethrin (beta=0.8 [0.3; 1.3], in MUg/g) and an
      increased risk of a detectable level of cyfluthrin (OR=4.7 [1.7; 12.9]) were
      observed in home dust, for indoor use of at least twice a year. Outdoor
      insecticide use at least once a year was associated with detection in dust of
      cypermethrin (OR=3.0 [1.3; 6.7]) and tetramethrin (OR=3.7 [1.6; 8.3]). Three
      positive and one negative correlations (out of 11) between urinary metabolite
      concentrations and home dust contents of their possible corresponding parent
      compounds were observed. The strength of this study lies in its concurrent use of
      biomarkers, environmental measurements, and potential sources of exposure. Its
      limitations include the use of a single urine sample and imprecise data about
      pyrethroid use in local agriculture.

PMID- 28453974
TI  - Influences of dissolved oxygen concentration on biocathodic microbial communities
      in microbial fuel cells.
AB  - Dissolved oxygen (DO) at cathodic interface is a critical factor influencing
      microbial fuel cells (MFC) performance. In this work, three MFCs were operated
      with cathode under different DO conditions: i) air-breathing (A-MFC); ii) water
      submerged (W-MFC) and iii) assisted by photosynthetic microorganisms (P-MFC). A
      plateau of maximum current was reached at 1.06+/-0.03mA, 1.48+/-0.06mA and 1.66+/
      0.04mA, increasing respectively for W-MFC, P-MFC and A-MFC. Electrochemical and
      microbiological tools (Illumina sequencing, confocal microscopy and biofilm
      cryosectioning) were used to explore anodic and cathodic biofilm in each MFC
      type. In all cases, biocathodes improved oxygen reduction reaction (ORR) as
      compared to abiotic condition and A-MFC was the best performing system.
      Photosynthetic cultures in the cathodic chamber supplied high DO level, up to
      16mgO2L-1, which sustained aerobic microbial community in P-MFC biocathode.
      Halomonas, Pseudomonas and other microaerophilic genera reached >50% of the total
      OTUs. The presence of sulfur reducing bacteria (Desulfuromonas) and purple non
      sulfur bacteria in A-MFC biocathode suggested that the recirculation of sulfur
      compounds could shuttle electrons to sustain the reduction of oxygen as final
      electron acceptor. The low DO concentration limited the cathode in W-MFC. A model
      of two different possible microbial mechanisms is proposed which can drive
      predominantly cathodic ORR.

PMID- 28453975
TI  - Synaptic plasticity in dendrites: complications and coping strategies.
AB  - The elaborate morphology, nonlinear membrane mechanisms and spatiotemporally
      varying synaptic activation patterns of dendrites complicate the expression,
      compartmentalization and modulation of synaptic plasticity. To grapple with this
      complexity, we start with the observation that neurons in different brain areas
      face markedly different learning problems, and dendrites of different neuron
      types contribute to the cell's input-output function in markedly different ways.
      By committing to specific assumptions regarding a neuron's learning problem and
      its input-output function, specific inferences can be drawn regarding the
      synaptic plasticity mechanisms and outcomes that we 'ought' to expect for that
      neuron. Exploiting this assumption-driven approach can help both in interpreting
      existing experimental data and designing future experiments aimed at
      understanding the brain's myriad learning processes.

PMID- 28453976
TI  - A Compton scattering setup for pulse shape discrimination studies in germanium
      detectors.
AB  - Pulse shape discrimination is an important handle to improve sensitivity in low
      background experiments. A dedicated setup was built to investigate the response
      of high-purity germanium detectors to single Compton scattered events. Using
      properly collimated gamma-ray sources, it is possible to select events with known
      interaction location. The aim is to correlate the position dependent signal shape
      with geometrical and electrical properties of the detector. We report on design
      and performance of the setup with a first look on data.

PMID- 28453977
TI  - Measurement of the effective energy of pulsed X-rays emitted from a Mather-type
      plasma focus device.
AB  - The current study examined the effective energy of pulsed x-rays emitted from a
      Mather-type plasma focus device with copper anodes at an energy range of 2-3kJ
      using x-ray transmission radiography. Aluminum filters of different thicknesses
      and dental x-ray film were used. When air gas was used at a constant voltage of
      21kV at 0.3, 0.6, 0.9 and 1.2 mbar, the effective energy of pulsed the x-ray was
      10.9, 10.7, 17.3 and 15.8keV, respectively. At 0.6 mbar of air, as the operating
      voltage increased to 19, 21 and 23kV, the effective energy of the x-ray radiation
      was 10.6, 10.7 and 12.4keV, respectively. Comprehensive investigation of the
      characteristics of x-ray emission from plasma focus devices makes it feasible to
      use this device as an intensive x-ray generator for medical and industrial
      purposes. The present study is a part of a program which is planned to realize
      these applications.

PMID- 28453978
TI  - Oxytocin attenuates social and non-social avoidance: Re-thinking the social
      specificity of Oxytocin.
AB  - Re-examining decades of the social construal of Oxytocin, the General Approach
      Avoidance Hypothesis of Oxytocin (GAAO) predicts that Oxytocin will modulate
      responding to emotionally-evocative and personally-relevant social and non-social
      stimuli due to its action on the neural substrate of approach and avoidance
      motivation. We report the first critical experimental test of GAAO predictions by
      means of a double-blind intra-nasal administration of Oxytocin vs. placebo in 90
      healthy adults (N=90, 50% women). As predicted, we found that among men and women
      for whom negative emotion (anxious arousal) is motivationally-relevant, intra
      nasal administration of Oxytocin reduced behavioral avoidance of emotionally
      evocative negatively-valenced social and non-social stimuli, but not closely
      matched emotionally-neutral stimuli. Findings cannot be explained by extant
      social theories of Oxytocin. We discuss the implications of the present findings
      for basic and translational clinical Oxytocin research.

PMID- 28453979
TI  - Effects of replacement of beef fat with interesterified palm kernel oil on the
      quality characteristics of Turkish dry-fermented sausage.
AB  - The objective of this study was to investigate the effects of replacing beef fat
      with enzymatic interesterified palm kernel oil (IPKO) on the quality
      characteristics and storage stability of sucuk (Turkish dry-fermented sausage).
      The partial (25, 50, 75%) and complete (100%) replacement of added beef fat with
      IPKO were carried out during sucuk processing. According to the study results,
      replacement of beef fat with IPKO resulted in significant increase in the
      concentrations of caprylic, capric, lauric and mryistic acid and decrease in the
      concentrations of stearic, oleic and linoleic acid in sucuk (P<0.05). Even though
      replacement with IPKO did not affect TBARS of sucuk dough, a slightly higher
      TBARS values were determined in sucuk manufactured with IPKO at the end of
      storage compared to control (P<0.05). Hardness, gumminess and chewiness values of
      sucuks were decreased with IPKO replacement (P<0.05). Replacement with IPKO
      increased moisture and a* and b*, decreased protein, fat and pH in sucuks at the
      end of fermentation (P<0.05).

PMID- 28453980
TI  - Effect of ultimate pH and ageing on thermal denaturation of bovine muscle
      proteins.
AB  - The thermal denaturation of proteins was evaluated in the natural state of bovine
      muscle using differential scanning calorimetry (DSC). The Longissimus lumborum
      muscle was selected according to ultimate pH (pHu) values classified into two
      groups: low pHu with values between 5.4 and 5.8, and intermediate pHu with values
      between 5.81 and 6.19. The muscles were cut and aged at 2 degrees C up to 21d
      post mortem. The three maximum temperatures of denaturation (Tmax1, Tmax2, Tmax3)
      found in muscle were evaluated, showing higher thermal stability in the
      intermediate pHu group, which could be an indicator of protection of proteins
      against aggregation or enzymatic activity. The thermal behavior of muscle
      proteins could be defined by biochemical factors that are affected by pHu of the
      muscle, however, further studies are necessary to explain this process, which
      could have a great impact on the understanding of the final tenderness achieved
      in meat.

PMID- 28453981
TI  - Facile synthesis of flower-like Ag3VO4/Bi2WO6 heterojunction with enhanced
      visible-light photocatalytic activity.
AB  - Constructing novel semiconductor heterojunctions is one of the most significant
      approaches to improving the photocatalytic performance of a photocatalyst.
      Herein, the Ag3VO4/Bi2WO6 heterojunction was prepared through in-situ anchoring
      Ag3VO4 nanoparticles (size: ~21nm) on the surface of Bi2WO6 microflowers
      (diameter: 2.5-4.5MUm) by a facile deposition route. The photocatalytic activity
      of these heterojunctions were studied by decomposing cationic dye rhodamine B
      (RhB), anionic dye methyl orange (MO) and neutral para-chlorophenol (4-CP) under
      visible light irradiation (lambda>400nm). Among all the tested catalysts, the
      heterojunction with a Ag3VO4/Bi2WO6 molar ratio of 0.15/1 displays the maximum
      activity with the RhB degradation rate constant of up to 0.0392min-1, a 6.7 or
      1.7 times more enhancement compared with the pure Bi2WO6 or Ag3VO4. It is found
      that the introduction of Ag3VO4 is in favor of suppressing the electron-hole pair
      recombination of Bi2WO6, leading to an enhanced photocatalytic activity with good
      stability. The photogenerated holes (h+) and superoxide radicals (O2-) play
      critical roles during the photocatalytic process. Ag3VO4/Bi2WO6 will have great
      potential in applications for environmental remediation due to the facile
      preparation method and superior photocatalytic activity.

PMID- 28453982
TI  - Effect of microstructure and surface hydroxyls on the catalytic activity of
      Au/AlOOH for formaldehyde removal at room temperature.
AB  - A series of Au/AlOOH catalysts was prepared by impregnating different AlOOH
      supports with Au precursor followed by NaBH4-assisted reduction, and examined
      their activity toward oxidation of indoor formaldehyde (HCHO) pollutant at room
      temperature. The AlOOH supports used were synthesized by microemulsion, microwave
      and hydrothermal methods. Among these supports the catalyst obtained by
      deposition of Au nanoparticles (NPs) on AlOOH prepared by microemulsion method
      (Au/AlOOH-m) exhibited the highest catalytic activity. Based on the detailed
      characterization of the catalysts, the microstructure of AlOOH support,
      dispersion and size of Au NPs, surface hydroxyls, and interactions between Au and
      the support are important factors controlling the efficient removal of HCHO at
      room temperature. The superior catalytic performance of Au/AlOOH-m is attributed
      to its larger specific surface area, small size of Au NP, large amount of
      reactive surface hydroxyls, and better adsorption properties of this support.
      This study shows not only the importance of the microstructure and surface
      hydroxyls on the oxidative degradation of HCHO on Au/AlOOH at room temperature,
      but also provides a new insight into rational synthesis of high-efficiency
      catalysts for removal of indoor air pollutants.

PMID- 28453983
TI  - Discovery and mechanism of action of Novel Baicalein modified derivatives as
      potent antihepatitis agent.
AB  - Anti-hepatitis B virus (HBV) activity was evaluated in HepG2 2.2.15 cells by
      novel Baicalein derivatives. The result showed that compounds 4k and 4h was found
      to be effective anti-HBV agent. Further, the effect of compounds 4k and 4h showed
      dose-dependent inhibition of HBV-DNA as compared to control together with
      significant inhibition of HbeAG and HbsAG expression in the tested dose. Both
      compounds showed considerable affinity against the HepG2.2.15 cells. Moreover,
      the docking study of compound 4k was carried out with HLA molecule showing
      excellent intermolecular interactions with the receptor via creation of numerous
      bonds with Ser5, Thr27, Asp29 and Phe8. The compound 4k showed significant effect
      on the HO-1 expression in HepG2.2.15 cells together with excellent anti-HBV
      activity in transgenic mouse confirmed by biochemical and histopathological
      parameters. Compound 4k also showed excellent pharmacokinetic profile in
      experimental animal and thus, provide a novel class of potent anti-HBV agents.

PMID- 28453985
TI  - Realising the dream of becoming a nurse: Underrepresented BSc nursing students
      experiences.
AB  - BACKGROUND: This paper describes the experiences of underrepresented BSc nursing
      students in realising the dream of becoming a nurse in one university. In the
      past ten years, pre-registration nurse education has become established within
      higher education in Ireland. This development includes promoting access and
      inclusion of students from traditionally underrepresented groups in higher
      education. A third of nursing students currently access places on programmes
      through routes specifically designed for underrepresented groups. METHODS: A
      qualitative descriptive study design provided an opportunity for student voices
      to be heard. Ethical approval was sought and granted. Eleven students were
      interviewed nearing completion of a four year BSc Nursing programme. Data
      analysis followed a thematic approach, in generating themes. FINDINGS: Three
      themes emerged from the data: taking the first steps; finding a way and getting
      through. Findings highlight participants' challenges in balancing study, clinical
      practice and family life in achieving and realising their dream of becoming a
      nurse. CONCLUSION: This study illustrates the nature and complexities of
      participants' experiences throughout the BSc Nursing programmes towards becoming
      university graduates, eligible for registration as a nurse. Students from
      underrepresented groups bring rich and diverse life experiences in preparation
      for and becoming caring practitioners. It highlights the individuality within
      participants' experiences and draws attention to the value of personalised
      support for students. An opportunity to encourage the development of emotional
      intelligence needs to be fostered within nurse education programmes. Creating
      positive learning environments is critical to supporting student understanding of
      compassionate patient centred care. Findings have relevance for global curriculum
      design and structures to support individual student centred engagement. Further
      research is required to consider how best to support students from
      underrepresented groups.

PMID- 28453984
TI  - Functional and genetic evidence that nucleoside transport is highly conserved in
      Leishmania species: Implications for pyrimidine-based chemotherapy.
AB  - Leishmania pyrimidine salvage is replete with opportunities for therapeutic
      intervention with enzyme inhibitors or antimetabolites. Their uptake into cells
      depends upon specific transporters; therefore it is essential to establish
      whether various Leishmania species possess similar pyrimidine transporters
      capable of drug uptake. Here, we report a comprehensive characterization of
      pyrimidine transport in L. major and L. mexicana. In both species, two
      transporters for uridine/adenosine were detected, one of which also transported
      uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2'deoxyuridine
      (5F,2'dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other
      transporter mediated uptake of adenosine, uridine, 5F,2'dUrd and thymidine and
      was designated Nucleoside Transporter 1 (NT1). To verify the reported L. donovani
      model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2
      gene encoding an inosine transporter, we cloned the corresponding L. major and L.
      mexicana genes, expressing each in T. brucei. Consistent with the L. donovani
      reports, the NT1-like genes of either species mediated the adenosine-sensitive
      uptake of [3H]-uridine but not of [3H]-inosine. Conversely, the NT2-like genes
      mediated uptake of [3H]-inosine but not [3H]-uridine. Among pyrimidine
      antimetabolites tested, 5-FU and 5F,2'dUrd were the most effective
      antileishmanials; resistance to both analogs was induced in L. major and L.
      mexicana. In each case it was found that the resistant cells had lost the
      transport capacity for the inducing drug. Metabolomics analysis found that the
      mechanism of action of 5-FU and 5F-2'dUrd was similar in both Leishmania species,
      with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine
      salvage system is highly conserved in Leishmania species - essential information
      for the development of pyrimidine-based chemotherapy.

PMID- 28453986
TI  - Facilitating smallholder tree farming in fragmented tropical landscapes:
      Challenges and potentials for sustainable land management.
AB  - Under changing land use in tropical Asia, there is evidence of forest product
      diversification through implementation of tree-based farming by smallholders.
      This paper assesses in two locations, West Java, Indonesia and eastern
      Bangladesh, current land use conditions from the perspective of smallholder
      farmers, the factors that facilitate their adoption of tree farming, and the
      potential of landscape-scale approaches to foster sustainable land management.
      Data were collected through rapid rural appraisals, focus group discussions,
      field observations, semi-structured interviews of farm households and key
      informant interviews of state agricultural officers. Land at both study sites is
      typically fragmented due to conversion of forest to agriculture and community
      settlement. Local land use challenges are associated with pressures of population
      increase, poverty, deforestation, shortage of forest products, lack of community
      scale management, weak tenure, underdeveloped markets, government decision-making
      with insufficient involvement of local people, and poor extension services.
      Despite these challenges, smallholder tree farming is found to be successful from
      farmers' perspectives. However, constraints of local food crop cultivation
      traditions, insecure land tenure, lack of capital, lack of knowledge, lack of
      technical assistance, and perceived risk of investing in land due to local
      conflict (in Bangladesh) limit farmers' willingness to adopt this land use
      alternative. Overcoming these barriers to adoption will require management at a
      landscape scale, including elements of both segregation and integration of land
      uses, supported by competent government policies and local communities having
      sufficiently high social capital.

PMID- 28453987
TI  - Calcium-rich biochar from the pyrolysis of crab shell for phosphorus removal.
AB  - Calcium-rich biochars (CRB) prepared through pyrolysis of crab shell at various
      temperatures were characterized for physicochemical properties and P removal
      potential. Elemental analysis showed that CRB was rich in calcium (22.91%
      36.14%), while poor in carbon (25.21%-9.08%). FTIR, XRD and TG analyses showed
      that calcite-based CRB was prepared at temperature <=600  degrees C, while lime
      based CRB was prepared at temperature >=700  degrees C. Phosphorus removal
      experiment showed that P removal efficiencies in 80 mg P/L phosphate solution and
      biogas effluent ranged from 26% to 11%, respectively, to about 100% and 63%,
      respectively, depending on the pyrolysis temperature of the resulting biochar.
      Specifically, compared to common used CaCO3 and Ca(OH)2, P removal potential of
      calcite-based CRB was much higher than that of CaCO3; while that of lime-based
      CRB was close to that of Ca(OH)2. These results suggested that CRB was competent
      for P removal/recovery from wastewater.

PMID- 28453988
TI  - Conservation program delivery in the southern U.S.: Preferences and interactions.
AB  - A lingering challenge in implementation of ecosystem-based planning is
      translating high-level conservation objectives to discrete management
      initiatives. Recent research underscores this, emphasizing the importance of the
      processes by which plans are developed and how programs to implement plans are
      delivered to stakeholders. This study contributes to the existing program design,
      research methodology, and conservation practice literature through an assessment
      of landowner and conservation practitioner relationships in the Gulf Coastal
      Plains and Ozarks (GCPO) region of the southern U.S. The study utilizes online
      and mail surveys to gather data on landowner interactions with conservation
      practitioner organizations and interactions between practitioner organizations
      themselves. Data from the surveys suggest different patterns of interaction as
      reported by landowners and those reported by practitioner organizations working
      in the region, with landowners generally interacting more with extension and
      industry organizations and conservation practitioners interacting more with state
      and federal agencies. Key informant data also allows for analysis of the
      conservation practitioner network in the GCPO region. Resulting analysis suggests
      a well-connected network among the state and federal organizations critical to
      development and delivery of conservation programs in the GCPO LCC region. Though
      such configurations may be beneficial for the diffusion of innovative practices
      across a network, they may nonetheless require continued efforts to coordinate
      activities at the regional scale, an important component of practice-driven,
      ecosystem-level management.

PMID- 28453989
TI  - Recovery of lithium from the effluent obtained in the process of spent lithium
      ion batteries recycling.
AB  - A novel process of lithium recovery as lithium ion sieve from the effluent
      obtained in the process of spent lithium-ion batteries recycling is developed.
      Through a two-stage precipitation process using Na2CO3 and Na3PO4 as
      precipitants, lithium is recovered as raw Li2CO3 and pure Li3PO4, respectively.
      Under the best reaction condition (both the amounts of Na2CO3 and Li3PO4vs. the
      theoretical ones are about 1.1), the corresponding recovery rates of lithium
      (calculated based on the concentration of the previous stage) are 74.72% and
      92.21%, respectively. The raw Li2CO3 containing the impurity of Na2CO3 is used to
      prepare LiMn2O4 as lithium ion sieve, and the tolerant level of sodium on its
      property is studied through batch tests of adsorption capacity and corrosion
      resistance. When the weight percentage of Na2CO3 in raw Li2CO3 is controlled less
      than 10%, the Mn corrosion percentage of LiMn2O4 decreases to 21.07%, and the
      adsorption capacity can still keep at 40.08 mg g-1. The results reveal that the
      conventional separation sodium from lithium may be avoided through the
      application of the raw Li2CO3 in the field of lithium ion sieve.

PMID- 28453990
TI  - Thermo-chemo-sonic pre-digestion of waste activated sludge for yeast cultivation
      to extract lipids for biodiesel production.
AB  - The low cost biosynthesis of microbial lipids are an efficient feedstock to
      replace plant based oil for biodiesel production. The present study objective is
      to explore the effect of thermo-chemo-sonic pre-digestion of municipal Waste
      Activated Sludge (WAS) to cultivate oleaginous L. starkeyi MTCC-1400 as a model
      organism to produce high yield biomass and lipid. Higher Suspended Solids (SS)
      reduction (20 and 15.71%) and Chemical Oxygen Demand (COD) solubilization (27.6
      and 22.3%) were achieved at a Specific Energy (SE) input of 5569 kJ/kg for WAS
      digested with NaOH and KOH, respectively. The maximum biomass of 17.52 g L-1 and
      lipid 64.3% dwt were attained in NaOH pre-digested sample. The analyzed lipid
      profile exhibited high content of palmitic acid (45.6%) and oleic acid (38.7%)
      which are more suitable for biofuel production. Thus, these results strongly
      motivate the use of pre-digested WAS as an efficient and economical substrate for
      biodiesel production.

PMID- 28453991
TI  - Advocacy coalitions and protected areas creation process: Case study in the
      Amazon.
AB  - Protected areas are the cornerstones of conservation policies worldwide. However,
      only few researches are led to analyse the way they emerge, except for
      criticising top-down governmental choices. Yet, the historical approach and
      strategic analysis of public policy building over the long term allows a better
      understanding of the stakes of action capacity of these policies. We therefore
      mobilize the advocacy coalition framework to show that protected areas creation
      is always due to coalitions of actors who belong to different professional fields
      and act at different scales but nevertheless share common stakes. On the basis of
      a comparative study in French and Brazilian Amazon, we show that if all
      coalitions for protected areas share a common objective of limited deforestation,
      they are still very different according to the type of conservation they promote
      (strict biodiversity conservation, population-based conservation or sustainable
      forest management). We also show that the ability of the coalitions to build
      efficient public policies is highly depending on internal factors (i.e. their
      ability to gather strategic resources) and on external factors (i.e. socio
      political context and international pressure). Finally, the comparative analysis
      of coalitions pleading for the same type of protected areas in two different
      countries allows us to insist on the importance of qualitative embedded
      researches when it comes to understand why some protected areas have more chances
      to reach environmental effectiveness in one socio-political context than in
      another one.

PMID- 28453992
TI  - Salinomycin overcomes radioresistance in nasopharyngeal carcinoma cells by
      inhibiting Nrf2 level and promoting ROS generation.
AB  - Radiotherapy is the most important treatment for nasopharyngeal carcinoma (NPC).
      Radioresistant cancer cells have been shown to potentially result in residual
      disease that can lead to recurrence and metastasis. Salinomycin (SAL) has been
      identified as a promising anticancer drug during chemical screening, but it is
      unclear whether SAL plays a role in radioresistance. The nuclear factor erythroid
      2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant
      system. There are currently numerous data indicating that Nrf2 has an important
      role in cancer radioresistance. In the present study, we found that SAL can
      reverse radioresistance in radioresistant SUNE1 (SUNE1IR) cells using a clone
      formation assay. In addition, SAL promoted radiation-induced apoptosis in
      radioresistant NPC cells. Our data show that radioresistant SUNE1IR cells
      exhibited a significant increase in the protein level of Nrf2 compared to
      parental cells, and SAL inhibited increased Nrf2 in SUNE1IR cells. Moreover, we
      knocked down Nrf2 with shRNA in CNE2 cells and Western blot analysis demonstrated
      that irradiation (IR)-induced increase in Nrf2 protein expression was
      significantly downregulated by SAL. The clone formation assay showed that Nrf2
      deficient CNE2 cells were more sensitive to IR than parental cells. Importantly,
      we confirmed that combination treatment of Nrf2-deficient CNE2 cells with SAL and
      IR markedly increased the level of reactive oxygen species (ROS) and DNA damage.
      Taken together, our findings demonstrate, for the first time, that SAL sensitized
      radioresistant cells to IR by inhibition of Nrf2 and the promotion of ROS
      generation in NPC. These results may contribute to the development of SAL-based
      therapy for NPC patients.

PMID- 28453993
TI  - Sexual violence interventions: Considerations for humanitarian settings.
AB  - Sexual and gender based violence may result in a range of destructive
      consequences to the individual, their family and the wider community. Addressing
      such violence and its immediate aftermath in circumstances of civil turmoil
      requires a timely, planned and coordinated multidisciplinary response. Such
      interventions need to be cognisant of, and address a range of challenges which
      might include economic barriers, religious and cultural divides, a dearth of
      respect for human rights and limited access or capacity of medical, policing and
      legal services. In addition to addressing the immediate humanitarian prerogatives
      of health and safety issues, further objectives include the provision of support
      and justice for victims and the goal of ending impunity for perpetrators of
      sexual violence. Forensic medicine and its practitioners have the potential to
      make significant contributions in this field.

PMID- 28453994
TI  - Synthesis and applications of benzohydroxamic acid-based histone deacetylase
      inhibitors.
AB  - This paper provides an overview of the synthesis and biological activity of the
      most representative benzohydroxamic acid-based histone deacetylase inhibitors
      published to date. Benzohydroxamic acids comprise an important class of HDAC
      inhibitors, and recently several of these structures have been evaluated in
      clinical trials for the treatment of a variety of cancers. In this overview,
      benzohydroxamic acids were divided in four different classes based on their
      reported selectivity towards zinc-dependent HDACs: a first and major class
      consists of HDAC6 selective inhibitors, a second class deals with pan-HDAC
      inhibitors, a third class comprises HDAC8 selective inhibitors and a fourth,
      minor class includes dual HDAC6/8 selective inhibitors. Through this approach,
      structure-activity relationships were identified for each class, which could help
      future researchers in the design and development of novel benzohydroxamic acid
      based HDAC inhibitors.

PMID- 28453995
TI  - Synthesis and mechanistic evaluation of novel N'-benzylidene-carbohydrazide-1H
      pyrazolo[3,4-b]pyridine derivatives as non-anionic antiplatelet agents.
AB  - Cardiovascular diseases (CVDs) account for over 17 million deaths globally each
      year, with atherosclerosis as the underlying cause of most CVDs. Herein we
      describe the synthesis and in vitro mechanistic evaluation of novel N'
      benzylidene-carbohydrazide-1H-pyrazolo[3,4-b]pyridines (3-22) designed as non
      anionic antiplatelet agents and presenting a 30-fold increase in potency compared
      to aspirin. The mechanism underlying their antiplatelet activity was elucidated
      by eliminating potential targets through a series of in vitro assays including
      light transmission aggregometry, clot retraction, and quantitative ELISA, further
      identifying the reduction in biosynthesis of thromboxane B2 as their main
      mechanism of action. The intrinsic fluorescence of the compounds permits their
      binding to platelet membranes to be readily monitored. In silico structure
      activity relationship, molecular docking and dynamics studies support the
      biological profile of the series revealing the molecular basis of their activity
      and their potential as future molecular therapeutic agents.

PMID- 28453996
TI  - Broca's region: A causal role in implicit processing of grammars with crossed non
      adjacent dependencies.
AB  - Non-adjacent dependencies are challenging for the language learning machinery and
      are acquired later than adjacent dependencies. In this transcranial magnetic
      stimulation (TMS) study, we show that participants successfully discriminated
      between grammatical and non-grammatical sequences after having implicitly
      acquired an artificial language with crossed non-adjacent dependencies.
      Subsequent to transcranial magnetic stimulation of Broca's region, discrimination
      was impaired compared to when a language-irrelevant control region (vertex) was
      stimulated. These results support the view that Broca's region is engaged in
      structured sequence processing and extend previous functional neuroimaging
      results on artificial grammar learning (AGL) in two directions: first, the
      results establish that Broca's region is a causal component in the processing of
      non-adjacent dependencies, and second, they show that implicit processing of non
      adjacent dependencies engages Broca's region. Since patients with lesions in
      Broca's region do not always show grammatical processing difficulties, the result
      that Broca's region is causally linked to processing of non-adjacent dependencies
      is a step towards clarification of the exact nature of syntactic deficits caused
      by lesions or perturbation to Broca's region. Our findings are consistent with
      previous results and support a role for Broca's region in general structured
      sequence processing, rather than a specific role for the processing of
      hierarchically organized sentence structure.

PMID- 28453997
TI  - Between a conditional's antecedent and its consequent: Discourse coherence vs.
      probabilistic relevance.
AB  - Reasoning with conditionals is central to everyday life, yet there is long
      standing disagreement about the meaning of the conditional. One example is the
      puzzle of so-called missing-link conditionals such as "if raccoons have no wings,
      they cannot breathe under water." Their oddity may be taken to show that
      conditionals require a connection between antecedent ("raccoons have no wings")
      and consequent ("they cannot breathe under water"), yet most accounts of
      conditionals attribute the oddity to natural-language pragmatics. We present an
      experimental study disentangling the pragmatic requirement of discourse coherence
      from a stronger notion of connection: probabilistic relevance. Results indicate
      that mere discourse coherence is not enough to make conditionals assertable.

PMID- 28453998
TI  - Sleep slow oscillation and plasticity.
AB  - It is well documented that sleep contributes to memory consolidation and it is
      also accepted that long-term synaptic plasticity plays a critical role in memory
      formation. The mechanisms of this sleep-dependent memory formation are unclear.
      Two main hypotheses are proposed. According to the first one, synapses are
      potentiated during wake; and during sleep they are scaled back to become
      available for the learning tasks in the next day. The other hypothesis is that
      sleep slow oscillations potentiate synapses that were depressed due to persistent
      activities during the previous day and that potentiation provides physiological
      basis for memory consolidation. The objective of this review is to group
      information on whether cortical synapses are up-scaled or down-scaled during
      sleep. We conclude that the majority of cortical synapses are up-regulated by
      sleep slow oscillation.

PMID- 28453999
TI  - Symptoms of obsessive-compulsive disorder predict cannabis misuse.
AB  - INTRODUCTION: Cannabis use has been linked to many psychological disorders. There
      is, however, a paucity of research investigating the link between cannabis use
      and obsessive-compulsive disorder (OCD). The present study sought to examine this
      link by exploring associations between severity of OCD symptoms, cannabis use,
      and cannabis misuse; determining whether these associations exist above and
      beyond symptoms of anxiety, depression, and stress; and testing the mediating
      role of cannabis coping motives (i.e., using cannabis to cope with negative
      affect and other problems). METHODS: A large sample of young adult cannabis users
      (n=430) completed an online survey containing measures of OCD symptoms, cannabis
      use, cannabis misuse, and cannabis use motives. RESULTS: Severity of OCD (as
      indexed by higher scores on the Obsessive-Compulsive Inventory-Revised) was
      unrelated to frequency and quantity of cannabis use, but it was significantly,
      positively related to increased cannabis misuse. These effects persisted after
      controlling for anxiety, depression, and stress. The specific feature of
      obsessing was found to consistently predict cannabis misuse. Finally, an indirect
      effect of severity of OCD on cannabis misuse via coping motives was discovered.
      CONCLUSIONS: Together, these findings indicate that there may be an association
      between OCD and cannabis misuse that is independent of anxiety, depression, and
      stress, and that is mediated by coping motives. Based on these findings, we
      recommend that individuals with OCD symptoms avoid using cannabis because they
      may be more vulnerable to the development of problematic use and cannabis use
      disorder.

PMID- 28454000
TI  - Models describing metronidazole pharmacokinetics in relation to hemodynamics in
      turkeys.
AB  - Linking haemodynamic (HD) and pharmacokinetic (PK) parameters provides much
      insight into interrelations between circulatory system and drug disposition. This
      effect is particularly pronounced in rapidly growing animals. Heart rate (HR),
      cardiac output (CO) and stroke volume (SV) are tightly linked with the animal's
      age and correlate with the increasing body weight (BW). The aim of this study was
      to establish and validate the relations between BW, HD and chosen PK parameters
      of metronidazole (MTZ) and its metabolite - hydroxymetronidazole (MTZ-OH) in
      growing turkeys. The study was carried out on broiler turkeys (BUT-9, n=26). All
      individuals were subjected to single dose PK studies four times, that is when the
      mean BW in the group reached: 1.4 (group A); 2.7 (group B); 5.5 (group C); 10.7kg
      (group D). Some PK parameters normalized with regard to HR were found to take
      constant values in all the age groups under investigation. CO<->1/MRT, SV<->1/MRT
      and SV<->MRT model was validated with regard to both metabolite and drug PK. This
      study proposed a model for the analysis of the relations HD<->BW and HD<->PK.
      Models developed in this study provide empirical evidence that HD affect the PK
      of MTZ and MTZ-OH in a different fashion.

PMID- 28454001
TI  - Bacterial community shift and improved performance induced by in situ preparing
      dual graphene modified bioelectrode in microbial fuel cell.
AB  - Dual graphene modified bioelectrode (D-GM-BE) was prepared by in situ microbial
      induced reduction of graphene oxide (GO) and polarity reversion in microbial fuel
      cell (MFC). Next Generation Sequencing technology was used to elucidate bacterial
      community shift in response to improved performance in D-GM-BE MFC. The results
      indicated an increase in the relative ratio of Proteobacteria, but a decrease of
      Firmicutes was observed in graphene modified bioanode (GM-BA); increase of
      Proteobacteria and Firmicutes were observed in graphene modified biocathode (GM
      BC). Genus analysis demonstrated that GM-BE was beneficial to enrich electrogens.
      Typical exoelectrogens were accounted for 13.02% and 8.83% in GM-BA and GM-BC.
      Morphology showed that both GM-BA and GM-BC formed 3D-like graphene/biofilm
      architectures and revealed that the biofilm viability and thickness would
      decrease to some extent when GM-BE was formed. D-GM-BE MFC obtained the maximum
      power density by 124.58+/-6.32mWm-2, which was 2.34 times over C-BE MFC.

PMID- 28454002
TI  - Characterization of lipid accumulation and lipidome analysis in the oleaginous
      yeasts Rhodosporidium azoricum and Trichosporon oleaginosus.
AB  - The influence of cultural conditions on lipid production was investigated in two
      species, Trichosporon oleaginosus and Rhodosporidium azoricum. We showed that
      nitrogen limitation is not the main factor triggering the mechanism of lipid
      accumulation in T. oleaginosus. Moreover, a scarce availability of oxygen
      negatively affected lipid synthesis to a lesser extent in T. oleaginosus than in
      R. azoricum. This highlights how the importance of controlling fermentation
      parameters is strictly linked to the yeast species employed. We showed that these
      parameters affect the activity of important enzymes, influencing the metabolic
      fluxes into different pathways, in particular pentose phosphate pathway and
      cytoplasmic pyruvate bypass. Furthermore, T. oleaginosus exhibited wider
      substrate flexibility, faster growth and higher lipid accumulation in fed-batch
      cultivation. Microbial oils obtained from both yeasts proved a valuable
      feedstock, alternative to vegetable oils, for advanced diesel biofuel production.

PMID- 28454003
TI  - Relative evaluation of micronutrients (MN) and its respective nanoparticles (NPs)
      as additives for the enhanced methane generation.
AB  - In the present work, effect of micro nutrients (MN) (NiCl2, Fe2O3, CoCl2,
      (NH4)6Mo7O24) was compared with nanoparticles (NPs) of respective MN with cattle
      manure (CM) slurry in single and bi-phasic anaerobic digestion (AD) at a
      hydraulic residence time (HRT) of 20days at a mesophilic temperature of 37+/-2
      degrees C for the generation of biogas with enhanced methane (70-80%).
      Experiments were also carried out with CM slurry as control. During single phase
      AD, highest biogas production of 0.16L/(gVS reduced) and 0.14L/(gVS reduced) was
      obtained from Fe3O4 NPs and CoCl2 MN respectively whereas in bi-phasic AD
      0.3L/(gVS reduced) and 0.2L/(gVS reduced) was obtained from NiO NPs and NiCl2 MN
      correspondingly. The results elucidated that NiCl2 (either as MN or NPs) yielded
      highest biogas in comparison with either control or other MN and NPs.

PMID- 28454004
TI  - Growth and phycocyanin synthesis in the heterotrophic microalga Galdieria
      sulphuraria on substrates made of food waste from restaurants and bakeries.
AB  - Galdieria sulphuraria 074G (Rhodophyta) was grown heterotrophically in defined
      medium and on amylolytic and proteolytic hydrolysed food waste from restaurants
      and bakeries. Substrate uptake, growth, and phycocyanin content were quantified
      in the cultures. The alga utilised carbohydrates and amino acids from the waste
      but ammonium and other inorganic nutrients were needed to stimulate phycocyanin
      synthesis. Highest specific phycocyanin contents (20-22mgg-1) were observed in
      cells grown at 25 degrees C or 34 degrees C on the food wastes. Growth inhibition
      was observed when the hydrolysates were used in quantities resulting in glucose
      concentrations of 10 and 50gL-1 for bakery and restaurant waste, respectively.
      Still, G. sulphuraria 074G grew and produced phycocyanin efficiently on food
      waste under adequate conditions and may potentially be utilised for synthesise of
      high-valuable products from food waste.

PMID- 28454005
TI  - Competitive sorption affinity of sulfonamides and chloramphenicol antibiotics
      toward functionalized biochar for water and wastewater treatment.
AB  - Competitive sorption of sulfamethazine (SMT), sulfamethoxazole (SMX),
      sulfathiazole (STZ) and chloramphenicol (CP) toward functionalized biochar (fBC)
      was highly pH dependent with maximum sorption at pH ~4.0-4.25. Equilibrium data
      were well represented by the Langmuir and Freundlich models in the order
      STZ>SMX>CP>SMT. Kinetics data were slightly better fitted by the pseudo second
      order model than pseudo first-order and intra-particle-diffusion models. Maximum
      sorptive interactions occurred at pH 4.0-4.25 through H-bonds formations for
      neutral sulfonamides species and through negative charge assisted H-bond (CAHB)
      formation for CP, in addition to pi-pi electron-donor-acceptor (EDA)
      interactions. EDA was the main mechanism for the sorption of positive
      sulfonamides species and CP at pH<2.0. Sorption of negative sulfonamides species
      and CP at pH>7.0 was regulated by H-bond formation and proton exchange with water
      by forming CAHB, respectively. The results suggested fBC to be highly efficient
      in removing antibiotics mixture.

PMID- 28454006
TI  - Bioanode as a limiting factor to biocathode performance in microbial electrolysis
      cells.
AB  - The bioanode is important for a microbial electrolysis cell (MEC) and its
      robustness to maintain its catalytic activity affects the performance of the
      whole system. Bioanodes enriched at a potential of +0.2V (vs. standard hydrogen
      electrode) were able to sustain their oxidation activity when the anode potential
      was varied from -0.3 up to +1.0V. Chronoamperometric test revealed that the
      bioanode produced peak current density of 0.36A/m2 and 0.37A/m2 at applied
      potential 0 and +0.6V, respectively. Meanwhile hydrogen production at the
      biocathode was proportional to the applied potential, in the range from -0.5 to 
      1.0V. The highest production rate was 7.4L H2/(m2 cathode area)/day at -1.0V
      cathode potential. A limited current output at the bioanode could halt the
      biocathode capability to generate hydrogen. Therefore maximum applied potential
      that can be applied to the biocathode was calculated as -0.84V without
      overloading the bioanode.

PMID- 28454007
TI  - Groundwater remediation from the past to the future: A bibliometric analysis.
AB  - Groundwater is an important component of terrestrial ecosystems and plays a role
      in geochemical cycling. Groundwater is also used for agricultural irrigation and
      for the domestic supply of drinking water in most nations. However, groundwater
      contamination has led to many research efforts on groundwater remediation
      technologies and strategies. This study evaluated a total of 5486 groundwater
      remediation-related publications from 1995 to 2015 using bibliometric technology
      and social network analysis, to provide a quantitative analysis and a global view
      on the current research trend and future research directions. Our results
      underline a strong research interest and an urgent need to remediate groundwater
      pollution due to the increasing number of both groundwater contamination and
      remediation publications. In the past two decades, the United States (U.S.)
      published 41.1% of the papers and it was the core country of the international
      collaboration network, cooperating with the other 19 most productive countries.
      Besides the active international collaboration, the funding agencies also played
      positive roles to foster the science and technology publications. With respect to
      the analysis of the distribution of funding agencies, the National Science
      Foundation of China sponsored most of the groundwater remediation research. We
      also identified the most productive journals, Environmental Science and
      Technology and Journal of Contaminant Hydrology, which published 334 and 259
      scientific articles (including research articles and reviews) over the past 20
      years, respectively. In addition to journal publications, a patent analysis was
      performed to show the impact of intellectual property protection on journal
      publications. Three major remediation technologies, including chemical oxidation,
      biodegradation and adsorption, have received increasing interest in both journal
      publication and patent development. Our results provide a valuable reference and
      global overview to identify the potential obstacles and opportunities for
      researchers who currently work on groundwater contamination, remediation and
      related topics.

PMID- 28454008
TI  - Reactions of hypoiodous acid with model compounds and the formation of iodoform
      in absence/presence of permanganate.
AB  - The kinetics for the reactions of hypoiodous acid (HOI) with various phenols
      (phenol, 4-nitrophenol, 4-hydroxybenzoic acid), 3-oxopentanedioic acid (3-OPA)
      and flavone were investigated in the pH range of 6.0-11.0. The apparent second
      order rate constants for the reactions of HOI with phenolic compounds, 3-OPA,
      flavone and citric acid at pH 8.0 are 10-107 M-1s-1, (4.0 +/- 0.3) * 103 M-1s-1,
      (2.5 +/- 0.2) * 103 M-1s-1 and <1 M-1s-1, respectively. The effect of buffer type
      and concentration was investigated with acetate, phosphate and borate. All tested
      buffers promote the HOI reactions with phenols. The percentage of iodine
      incorporation for various (hydroxyl)phenolic compounds and two NOM extracts
      ranges from 5% to 98%, indicating that electrophilic aromatic substitution and/or
      electron transfer can occur. The extent of these reactions depends on the number
      and relative position of the hydroxyl moieties on the phenolic compounds.
      Iodoform formation rates increase with increasing pH and iodoform yields increase
      from 9% to 67% for pH 6.0-10.0 for the HOI/3-OPA reactions. In the
      permanganate/HOI/3-OPA and permanganate/iodide/3-OPA system at pH < 8.0, iodoform
      formation is elevated compared to the HOI/3-OPA system in absence of
      permanganate. For pH > 8.0, in presence of permanganate, iodoform formation is
      significantly inhibited and iodate formation enhanced, which is due to a faster
      permanganate-mediated HOI disproportionation to iodate compared to the iodination
      process. The production of reactive iodine in real waters containing iodide in
      contact with permanganate may lead to the formation of iodinated organic
      compounds.

PMID- 28454009
TI  - Environmental risk assessment of effluents as a whole emerging contaminant:
      Efficiency of alternative tertiary treatments for wastewater depuration.
AB  - Emerging contaminants (ECs) and regulated compounds (RCs) from three different
      WWTP effluents were measured in the current study. The efficiency of two tertiary
      treatments, Photobiotreatment (PhtBio) and Multi-Barrier Treatment (MBT), for
      removing contaminants was determined. Results indicated different percentages of
      removal depending on the treatment and the origin of the effluent. Risk Quotients
      (RQs) were determined for different species of algae, Daphnia, and fish. RQ
      results revealed diverse risk values depending on the bioindicator species.
      Tonalide, galaxolide (fragrances), and ofloxacin (antibiotic) were the most
      persistent and harmful substances in tested effluents. "Negligible risk" category
      was reached since a wide diversity of ECs were removed by MBT with high removal
      percentages. Contrarily, PhtBio was effective only in the depuration of certain
      chemical compounds, and its efficiency depended on the composition of the raw
      effluent.

PMID- 28454010
TI  - How economic recessions and unemployment affect illegal drug use: A systematic
      realist literature review.
AB  - BACKGROUND: Economic recessions may influence illegal drug use via different
      mechanisms, for example increased use due to more psychological distress or
      decreased use due to lower incomes and purchasing power. This paper reviews the
      literature on how economic recessions and unemployment affect the use of illegal
      drugs among adults. METHODS: We conducted a systematic realist literature review,
      which is an explanatory method that aims to understand underlying mechanisms that
      connect an event to an outcome in a specific context. A systematic search was
      performed in EconLit, Embase, Medline, PsycINFO, SocIndex, and Web of Science for
      studies examining mechanisms explaining how recessions or unemployment affect
      illegal drug use. RESULTS: We synthesized 28 studies published between 1990 and
      2015. Most evidence (17 studies) was found for the counter-cyclical mechanism
      that recessions and unemployment increase psychological distress, which increases
      drug use. Mainly supportive evidence for this mechanism was found in several high
      quality studies, in different contexts, and in a diverse number of countries and
      samples. In contrast, decreased income did not seem to decrease drug use (10
      studies). Little evidence was available on the non-working time mechanism (4
      studies) and the social exclusion mechanism (5 studies). Most of the studies that
      did examine these latter mechanisms confirmed the hypothesized counter-cyclical
      associations. CONCLUSION: The current evidence is in line with the hypothesis
      that drug use increases in times of recession because unemployment increases
      psychological distress which increases drug use. During times of recession,
      psychological support for those who lost their job and are vulnerable to drug use
      (relapse) is likely to be important.

PMID- 28454011
TI  - Nicotine and e-cigarettes: Rethinking addiction in the context of reduced harm.

PMID- 28454013
TI  - MRI-related magnetic field exposures and risk of commuting accidents - A cross
      sectional survey among Dutch imaging technicians.
AB  - BACKGROUND: Imaging technicians working with magnetic resonance imaging (MRI) may
      experience acute effects such as vertigo or dizziness when being exposed. A
      previous study also reported an increased risk of accidents in MRI exposed staff.
      OBJECTIVES: We aimed at evaluating commuting accident risk in Dutch imaging
      technicians. METHODS: Of invited imaging technicians, 490 (29%) filled in a
      questionnaire pertaining to (near) accidents when driving or riding a bike,
      health, lifestyle and work practices. We used logistic regression to evaluate the
      association between exposure to MRI-related electromagnetic fields and risk of
      commuting (near) accidents in the year prior to the survey, adjusted for a range
      of potential confounders. RESULTS: Our cross-sectional study indicated an
      increased risk of (near) accidents if imaging technicians had worked with MRI in
      the year prior to the survey (odds ratio OR 2.13, 95%CI 1.23-3.69). Risks were
      higher in persons who worked with MRI more often (OR 2.32, 95%CI 1.25-4.31)
      compared to persons who worked sometimes with MRI (OR 1.91, 95%CI 0.98-3.72), and
      higher in those who had likely experienced higher peak exposures to static and
      time-varying magnetic fields (OR 2.18, 95%CI 1.06-4.48). The effect was seen on
      commuting accidents that had occurred on the commute from home to work as well as
      accidents from work to home or elsewhere. CONCLUSION: Imaging technicians working
      with MRI scanners may be at an increased risk of commuting (near) accidents. This
      result needs confirmation and potential risks for other groups (volunteers,
      patients) should be investigated.

PMID- 28454012
TI  - Spatial clustering of childhood leukaemia with the integration of the Paediatric
      Environmental History.
AB  - BACKGROUND: Leukaemia remains the most common type of paediatric cancer and its
      aetiology remains unknown, but considered to be multifactorial. It is suggested
      that the initiation in utero by relevant exposures and/or inherited genetic
      variants and, other promotional postnatal exposures are probably required to
      develop leukaemia. This study aimed to map the incidence and analyse possible
      clusters in the geographical distribution of childhood acute leukaemia during the
      critical periods and to evaluate the factors that may be involved in the
      aetiology by conducting community and individual risk assessments. MATERIALS AND
      METHODS: We analysed all incident cases of acute childhood leukaemia (<15 years)
      diagnosed in a Spanish region during the period 1998-2013. At diagnosis, the
      addresses during pregnancy, early childhood and diagnosis were collected and
      codified to analyse the spatial distribution of acute leukaemia. Scan statistical
      test methodology was used for the identification of high-incidence spatial
      clusters. Once identified, individual and community risk assessments were
      conducted using the Paediatric Environmental History. RESULTS: A total of 158
      cases of acute leukaemia were analysed. The crude rate for the period was 42.7
      cases per million children. Among subtypes, acute lymphoblastic leukaemia had the
      highest incidence (31.9 per million children). A spatial cluster of acute
      lymphoblastic leukaemia was detected using the pregnancy address (p<0.05). The
      most common environmental risk factors related with the aetiology of acute
      lymphoblastic leukaemia, identified by the Paediatric Environmental History were:
      prenatal exposure to tobacco (75%) and alcohol (50%); residential and community
      exposure to pesticides (62.5%); prenatal or neonatal ionizing radiation (42.8%);
      and parental workplace exposure (37.5%) CONCLUSIONS: Our study suggests that
      environmental exposures in utero may be important in the development of childhood
      leukaemia. Due to the presence of high-incidence clusters using pregnancy
      address, it is necessary to introduce this address into the childhood cancer
      registers. The Paediatric Environmental History which includes pregnancy address
      and a careful and comprehensive evaluation of the environmental exposures will
      allow us to build the knowledge of the causes of childhood leukaemia.

PMID- 28454014
TI  - Reduced mouse allergen is associated with epigenetic changes in regulatory genes,
      but not mouse sensitization, in asthmatic children.
AB  - Chronic exposure to mouse allergen may contribute greatly to the inner-city
      asthma burden. We hypothesized that reducing mouse allergen exposure may modulate
      the immunopathology underlying symptomatic pediatric allergic asthma, and that
      this occurs through epigenetic regulation. To test this hypothesis, we studied a
      cohort of mouse sensitized, persistent asthmatic inner-city children undergoing
      mouse allergen-targeted integrated pest management (IPM) vs education in a
      randomized controlled intervention trial. We found that decreasing mouse allergen
      exposure, but not cockroach, was associated with reduced FOXP3 buccal DNA
      promoter methylation, but this was unrelated to mouse specific IgE production.
      This finding suggests that the environmental epigenetic regulation of an
      immunomodulatory gene may occur following changing allergen exposures in some
      highly exposed cohorts. Given the clinical and public health importance of inner
      city pediatric asthma and the potential impact of environmental interventions,
      further studies will be needed to corroborate changes in epigenetic regulation
      following changing exposures over time, and determine their impact on asthma
      morbidity in susceptible children.

PMID- 28454015
TI  - Air pollution characteristics and health risks in Henan Province, China.
AB  - Events of severe air pollution occurred frequently in China recently, thus
      understanding of the air pollution characteristics and its health risks is very
      important. In this work, we analyzed a two-year dataset (March 2014 - February
      2016) including daily concentrations of six criteria pollutants (PM2.5, PM10, CO,
      SO2, NO2, and O3) from 18 cities in Henan province. Results reveal the serious
      air pollution status in Henan province, especially the northern part, and
      Zhengzhou is the city with the worst air quality. Annual average PM2.5
      concentrations exceed the second grade of Chinese Ambient Air Quality Standard
      (75MUg/m3) at both 2014 and 2015. PM2.5 is typically the major pollutant, but
      ozone pollution can be significant during summer. Furthermore, as the commonly
      used air quality index (AQI) neglects the mutual health effects from multiple
      pollutants, we introduced the aggregate air quality index (AAQI) and health-risk
      based air quality index (HAQI) to evaluate the health risks. Results show that
      based on HAQI, the current AQI system likely significantly underestimate the
      health risks of air pollution, highlighting that the general public may need
      stricter health protection measures. The population-weighted two-year average
      HAQI data further demonstrates that all population in the studied cities in Henan
      province live with polluted air - 72% of the population is exposed to air that is
      unhealthy for sensitive people, while 28% of people is exposed to air that can be
      harmful to healthy people; and the health risks are much greater during winter
      than during other seasons. Future works should further improve the HAQI
      algorithm, and validate the links between the clinical/epidemiologic data and the
      HAQI values.

PMID- 28454016
TI  - Bohr effect of native and chemically modified hemoglobins: Quantitative analyses
      based on the Wyman equation.
AB  - Thirteen histidines and the alpha-chain terminal amino group (ACTA) make all of
      the contributions to the Bohr effect of human hemoglobin. The pKas of the 13
      histidines in carbonmonoxy- and deoxyhemoglobin are known from 1H NMR studies.
      Those of ACTA are not so precisely known. We employed the Wyman equation and the
      13 histidine pairs of pKas to determine the pKas of ACTA by curve-fitting to
      hemoglobin Bohr effect data. Using all 14 pairs of pKas as preliminary data, we
      employed the Wyman equation to fit the Bohr data for hemoglobin chemically
      modified at Cys93beta with cystamine, cystine and iodoacetamide. We demonstrate
      quantitatively that the reduction of the Bohr effect upon chemical modification
      is due to three negatively contributing Bohr groups: His2beta, His77beta and
      His143beta. These make twice their normal contributions to the Bohr effect in
      unmodified hemoglobin. We also find that the ACTA pKas increase with increasing
      ionic strength.

PMID- 28454017
TI  - The nexus between urbanization and PM2.5 related mortality in China.
AB  - The launch of China's new national urbanization plan, coupled with increasing
      concerns about air pollution, calls for better understandings of the nexus
      between urbanization and the air pollution-related health. Based on refined
      estimates of PM2.5 related mortality in China, we developed an Urbanization
      Excess Deaths Elasticity (U-EDE) indicator to measure the marginal PM2.5 related
      mortality caused by urbanization. We then applied statistical models to estimate
      U-EDE and examined the modification effects of income on U-EDE. Urbanization in
      China between 2004 and 2012 led to increased PM2.5 related mortality. A 1%
      increase in urbanization was associated with a 0.32%, 0.14%, and 0.50% increase
      in PM2.5 related mortality of lung cancer, stroke, and ischemic heart disease. U
      EDEs were modified by income with an inverted U curve, i.e., lower marginal
      impacts at the lowest and highest income levels. In addition, we projected the
      future U-EDE trend of China as a whole and found that China had experienced the
      peak of U-EDE and entered the second half of the inverted U-shaped curve. In the
      near future, national average U-EDE in China will decline along with the
      improvement of income level if no dramatic changes happen. However, the decreased
      U-EDE only implies that marginal PM2.5-related mortality brought by urbanization
      would decrease in China. Total health damage of urbanization will keep going up
      in the predictable future because the U-EDE is always positive.

PMID- 28454018
TI  - Chemical characteristic of PM2.5 emission and inhalational carcinogenic risk of
      domestic Chinese cooking.
AB  - To illustrate chemical characteristic of PM2.5 emission and assess inhalational
      carcinogenic risk of domestic Chinese cooking, 5 sets of duplicate cooking
      samples were collected, using the most used 5 types of oil. The mass abundance of
      14 elements, 5 water-soluble ions, organic carbon (OC), elemental carbon (EC) and
      11 polycyclic aromatic hydrocarbons (PAHs) were calculated; the signature and
      diagnostic ratio of cooking in the domestic kitchen were analyzed; and
      carcinogenic risks of heavy metals and PAHs via inhalation were assessed in two
      scenarios. The analysis showed that OC was the primary composition in the
      chemical profile; Na was the most abundant element that might be due to the usage
      of salt; Cr and Pb, NO3- and SO42-, Phe, FL and Pyr were the main heavy
      metals/water-soluble ions/PAHs, respectively. Phe and FL could be used to
      separate cooking and stationary sources, while diagnostic ratios of BaA/(BaA +
      CHR), BaA/CHR, BaP/BghiP and BaP/BeP should be applied with caution, as they were
      influenced by various cooking conditions. Carcinogenic risks of heavy metals and
      PAHs were evaluated in two scenarios, simulating the condition of cooking with no
      ventilation and with the range hood on, respectively. The integrated risk of
      heavy metals and PAHs was 2.7 * 10-3 and 5.8 * 10-6, respectively, during cooking
      with no ventilation. While with the usage of range hood, only Cr(VI), As and Ni
      might induce potential carcinogenic risk. The difference in the chemical
      abundance in cooking sources found between this and other studies underlined the
      necessity of constructing locally representative source profiles under real
      conditions. The comparison of carcinogenic risk suggested that the potentially
      adverse health effects induced by inorganic compositions from cooking sources
      should not be ignored. Meanwhile, intervention methods, such as the operation of
      range hood, should be applied during cooking for health protection.

PMID- 28454019
TI  - Adsorption of carbon dots onto Al2O3 in aqueous: Experimental and theoretical
      studies.
AB  - Increasing interests in carbon dots (CDs) research resulted in the increased
      production of CDs and the risk to be released into the environment, including
      surface water and groundwater. To assess the environmental behavior of CDs, the
      stability of CDs in aqueous solutions were first examined by different
      environmental conditions, followed by the systematic investigation of the
      adsorption behaviors of CDs onto Al2O3 surface. Electrostatic interactions were
      considered as the dominant forces in CDs adsorption onto Al2O3 process, which
      were further confirmed by controlling experiments as compared with other minerals
      or oxides, such as montmorillonite, kaolinite and SiO2. Theoretical calculations
      and characterization of Al2O3/CDs revealed chemisorptions exist in the adsorption
      process. Our investigation results provided fundamental understanding towards the
      interaction of CDs with Al2O3 surface, and potential fate of CDs under natural
      conditions in aquatic environment, as well as in soils and sediments.

PMID- 28454020
TI  - Toxicity of TiO2, in nanoparticle or bulk form to freshwater and marine
      microalgae under visible light and UV-A radiation.
AB  - Use of titanium dioxide nanoparticles (TiO2 NPs) has become a part of our daily
      life and the high environmental concentrations predicted to accumulate in aquatic
      ecosystems are cause for concern. Although TiO2 has only limited reactivity, at
      the nanoscale level its physico-chemical properties and toxicity are different
      compared with bulk material. Phytoplankton is a key trophic level in fresh and
      marine ecosystems, and the toxicity provoked by these nanoparticles can affect
      the structure and functioning of ecosystems. Two microalgae species, one
      freshwater (Chlamydomonas reinhardtii) and the other marine (Phaeodactylum
      tricornutum), have been selected for testing the toxicity of TiO2 in NP and
      conventional bulk form and, given its photo-catalytic properties, the effect of
      UV-A was also checked. Growth inhibition, quantum yield reduction, increase of
      intracellular ROS production, membrane cell damage and production of exo
      polymeric substances (EPS) were selected as variables to measure. TiO2 NPs and
      bulk TiO2 show a relationship between the size of agglomerates and time in
      freshwater and saltwater, but not in ultrapure water. Under two treatments, UV-A
      (6 h per day) and no UV-A exposure, NPs triggered stronger cytotoxic responses
      than bulk material. TiO2 NPs were also associated with greater production of
      reactive oxygen species and damage to membrane. However, microalgae exposed to
      TiO2 NPs and bulk TiO2 under UV-A were found to be more sensitive than in the
      visible light condition. The marine species (P. tricornutum) was more sensitive
      than the freshwater species, and higher Ti internalization was measured.
      Exopolymeric substances (EPS) were released from microalgae in the culture media,
      in the presence of TiO2 in both forms. This may be a possible defense mechanism
      by these cells, which would enhance processes of homoagglomeration and settling,
      and thus reduce bioavailability.

PMID- 28454021
TI  - Reactive mineral removal relative to soil organic matter heterogeneity and
      implications for organic contaminant sorption.
AB  - Soil organic matter (SOM) is generally treated as a static compartment of soil in
      pollutant fate studies. However, SOM might be altered or fractionated in soil
      systems, and the details of SOM property/composition changes when coupled with
      contaminant behavior are unknown. In this study, a mild acid treatment was
      adopted to remove reactive minerals and partially remove SOM components. After
      acid treatment, biomarker signatures showed that lignin-derived phenols were
      released and black carbon (as suggested by benzene-polycarboxylic acids) and
      lipids were enriched. The biomarker information was consistent with common bulk
      chemical characterization. The sorption coefficient Kd for PHE was two times
      higher after acid treatment, whereas Kd for OFL was three times lower. The
      organic carbon normalized sorption coefficient KOC values for PHE were higher for
      soils after acid treatment, indicating stronger interactions between PHE and SOM.
      The linear regression line between Kd and fOC for OFL showed lower intercepts and
      slopes after reactive mineral removal, suggesting a decreased contribution of
      minerals and reduced dependence on SOM. These results were attributed to the
      release of polar compositions in SOM accompanied by reactive mineral removal. Our
      results suggest that the mobility of ionic organic contaminants increases,
      whereas that of hydrophobic organic contaminants decreases after acid treatment
      with respect to reactive mineral depletion. This study emphasized that new
      insights into the coupling of SOM dynamics should be incorporated into organic
      contaminant behavior studies. SOM molecular biomarkers offer a useful technique
      for correlating SOM composition and sorption property changes.

PMID- 28454022
TI  - Quantitative analysis of adsorptive interactions of ionic and neutral
      pharmaceuticals and other chemicals with the surface of Escherichia coli cells in
      aquatic environment.
AB  - Since Escherichia coli is ubiquitous in nature and has been applied to
      biological, chemical, and environmental processes, molecular-level understanding
      of adsorptive interactions between chemicals and the bacterial surface is of
      great importance. To characterise the adsorption properties of the surface of E.
      coli cells in aquatic environment, the binding affinities (log Kd) of calibration
      compounds were experimentally measured, and then based on the values and
      numerically well-defined molecular interaction forces, i.e. linear free energy
      relationship (LFER) descriptors, a predictive model was developed. The examined
      substances are composed of cations, anions, and neutral compounds, and the used
      LFER descriptors are excess molar refraction (E), dipolarity/polarisability (S),
      H-bonding acidity (A) and basicity (B), McGowan volume (V), and coulombic
      interactions of cations (J+) and anions (J-). In experimental results, adsorption
      of anions on the bacterial surface was not observed, while cations exhibited high
      affinities. In case of neutral compounds, their low quantities were adsorbed,
      however whose affinities were mostly lower than those of cations. In a LFER
      study, it was shown that cationic interaction term has the best correlation in R2
      of 0.691 and sequential additions of S, A, and V help to increase the prediction
      accuracy. The LFER model (log Kd = - 0.72-0.79 S + 0.81 A + 0.41 V + 0.85 J+)
      could predict the log Kd in R2 of 0.871 and SE of 0.402 log unit, and then to
      check robustness and predictability of the model, we internally validated it by a
      leave-one-out cross validation (Q2LOO) study. As a result, the Q2LOO value was
      estimated to be 0.826, which was larger than standard of model acceptability
      (>0.5).

PMID- 28454023
TI  - Toxicity and accumulation of Copper oxide (CuO) nanoparticles in different life
      stages of Artemia salina.
AB  - Metal nanoparticles production rate and its applications have raised concerns
      about their release and toxicity to the aquatic and terrestrial organisms. The
      primary size of Copper Oxide nanoparticles (CuO NP's) was found to be 114+/-36nm
      using Scanning Electron Microscopy (SEM) and a significant increase in the
      hydrodynamic diameter of CuO NP was seen within 1h of interaction. The median
      lethal concentration (LC50) values obtained from the acute toxicity studies on
      different life stages of Artemia salina was found to be 61.4, 35, 12.2 and
      175.2mg/L for 1d, 2d, 7d old and adult, respectively. The toxicity associated
      changes in biochemical markers such as Catalase, Reduced glutathione and
      Glutathione-S-Transferase were evident. The accumulation of Cu nanoparticles into
      the gut of Artemia salina was the major reason for toxicity. This study
      demonstrate the toxicity of CuO NPs to Artemia salina, and the obtained results
      necessitate the detailed investigation on the possible eco-toxicological
      implication of these nanomaterials.

PMID- 28454024
TI  - Disentangling the effects of species diversity, and intraspecific and
      interspecific tree size variation on aboveground biomass in dry zone homegarden
      agroforestry systems.
AB  - The biodiversity - aboveground biomass relationship has been intensively studied
      in recent decades. However, no consensus has been arrived to consider the
      interplay of species diversity, and intraspecific and interspecific tree size
      variation in driving aboveground biomass, after accounting for the effects of
      plot size heterogeneity, soil fertility and stand quality in natural forest
      including agroforests. We tested the full, partial and no mediations effects of
      species diversity, and intraspecific and interspecific tree size variation on
      aboveground biomass by employing structural equation models (SEMs) using data
      from 45 homegarden agroforestry systems in Sri Lanka. The full mediation effect
      of either species diversity or intraspecific and interspecific tree size
      variation was rejected, while the partial and no mediation effects were accepted.
      In the no mediation SEM, homegarden size had the strongest negative direct effect
      (beta=-0.49) on aboveground biomass (R2=0.65), followed by strong positive direct
      effect of intraspecific tree size variation (beta=0.32), species diversity
      (beta=0.29) and interspecific tree size variation (beta=0.28). Soil fertility had
      a negative direct effect on interspecific tree size variation (beta=-0.31). Stand
      quality had a significant positive total effect on aboveground biomass
      (beta=0.28), but homegarden size had a significant negative total effect (beta=
      0.62), while soil fertility had a non-significant total effect on aboveground
      biomass. Similar to the no mediation SEM, the partial mediation SEMs had
      explained almost similar variation in aboveground biomass because species
      diversity, and intraspecific and interspecific tree size variation had non
      significant indirect effects on aboveground biomass via each other. Our results
      strongly suggest that a multilayered tree canopy structure, due to high
      intraspecific and interspecific tree size variation, increases light capture and
      efficient utilization of resources among component species, and hence, support
      the niche complementarity mechanism via plant-plant interactions.

PMID- 28454025
TI  - Review and analysis of strengths and weaknesses of agro-ecosystem models for
      simulating C and N fluxes.
AB  - Biogeochemical simulation models are important tools for describing and
      quantifying the contribution of agricultural systems to C sequestration and GHG
      source/sink status. The abundance of simulation tools developed over recent
      decades, however, creates a difficulty because predictions from different models
      show large variability. Discrepancies between the conclusions of different
      modelling studies are often ascribed to differences in the physical and
      biogeochemical processes incorporated in equations of C and N cycles and their
      interactions. Here we review the literature to determine the state-of-the-art in
      modelling agricultural (crop and grassland) systems. In order to carry out this
      study, we selected the range of biogeochemical models used by the CN-MIP
      consortium of FACCE-JPI (http://www.faccejpi.com): APSIM, CERES-EGC, DayCent,
      DNDC, DSSAT, EPIC, PaSim, RothC and STICS. In our analysis, these models were
      assessed for the quality and comprehensiveness of underlying processes related to
      pedo-climatic conditions and management practices, but also with respect to time
      and space of application, and for their accuracy in multiple contexts. Overall,
      it emerged that there is a possible impact of ill-defined pedo-climatic
      conditions in the unsatisfactory performance of the models (46.2%), followed by
      limitations in the algorithms simulating the effects of management practices
      (33.1%). The multiplicity of scales in both time and space is a fundamental
      feature, which explains the remaining weaknesses (i.e. 20.7%). Innovative aspects
      have been identified for future development of C and N models. They include the
      explicit representation of soil microbial biomass to drive soil organic matter
      turnover, the effect of N shortage on SOM decomposition, the improvements related
      to the production and consumption of gases and an adequate simulations of gas
      transport in soil. On these bases, the assessment of trends and gaps in the
      modelling approaches currently employed to represent biogeochemical cycles in
      crop and grassland systems appears an essential step for future research.

PMID- 28454026
TI  - Textural characteristics and sedimentary environment of sediment at eroded and
      deposited regions in the severely eroded coastline of Batu Pahat, Malaysia.
AB  - This study investigates the textural characteristics of sediments collected at
      eroded and deposited areas of highly severed eroded coastline of Batu Pahat,
      Malaysia. Samples were taken from systematically selected 23 locations along the
      67km stretch of coastline and are extended to the fluvial sediments of the main
      river of Batu Pahat. Grain size distribution analysis was conducted to identify
      its textural characteristics and associated sedimentary transport behaviours.
      Sediments obtained along the coastline were fine-grained material with averaged
      mean size of 7.25 phi, poorly sorted, positively skewed and has wide
      distributions. Samples from eroded and deposition regions displayed no
      distinctive characteristics and exhibited similar profiles. The high energy
      condition transported the sediments as suspension, mostly as pelagic and the
      sediments were deposited as shallow marine and agitated deposits. The fluvial
      sediments of up to 3km into the river have particularly similar profile of
      textural characteristics with the neighbouring marine sediments from the river
      mouth. Profiles were similar with marine sediments about 3km opposite the main
      current and can go up to 10km along the current of Malacca Straits.

PMID- 28454027
TI  - Levels and risk factors for urinary metabolites of polycyclic aromatic
      hydrocarbons in children living in Chongqing, China.
AB  - AIMS: Since childhood exposure to polycyclic aromatic hydrocarbons (PAHs) have
      been associated with a variety of adverse health outcomes, the aims of this study
      were to1) document PAH exposure levels among children in Chongqing, China by
      measuring urinary concentrations of four PAH metabolites, 1-hydroxypyrene (1
      OHPyr), 2-hydroxynaphthalene (2-OHNap), 2-hydroxyfluorine (2-OHFlu) and 9
      hydroxyphenanthrene (9-OHPhe), and 2) assess the associations of urinary
      concentrations of these PAH metabolites with risk factors related to sources of
      PAHs inhalation and ingestion exposures and with personal attributes such as sex,
      age, and BMI. METHODS: The present study is a cross-sectional analysis using data
      drawn from the third follow up of a longitudinal study. Purposive sampling was
      used with all students in grades one to four in four schools being eligible to
      participate. The baseline survey included a total of 1237 students 5.8 to
      12.2years of age. At the third follow up survey, 1.5years after the baseline
      survey, 1230 of the children had a physical exam and provided urine samples.
      Their parents completed a questionnaire including social-demographic information
      and possible sources of children's exposure to PAHs. Urine samples were measured
      for the four OH-PAHs using an HPLC-MS/MS technique. Concentrations were corrected
      by specific gravity. Linear regression analysis was used to investigate factors
      related to sources of PAHs exposure. RESULTS: The urinary concentrations were
      highest for 9-OHPhe (median at the range of 3661ng/L), followed by 2-OHNap
      (3189ng/L), 2-OHFlu (1116ng/L), and 1-OHPyr (250ng/L). In multiple linear
      regressions, being female (P=0.04), school location near a thermal power plant
      (P=0.02) and higher maternal age at birth (P<0.01) were associated with increased
      concentrations of urinary 1-OHPyr; no significant associations were found for 2
      OHNap; school location near a thermal power plant (P<0.01) and lower family
      income (P<0.01) were associated with increased concentrations of urinary 2-OHFlu;
      higher age (P<0.01), school location near a thermal power plant (P=0.01),
      frequent consumption of smoked foods (P=0.04) and lower family income (P=0.07)
      were all found to be associated with increased concentrations of 9-OHPhe.
      CONCLUSIONS: Urinary concentrations of OH-PAHs, especially 9-OHPhe, were elevated
      in Chongqing Children compared to children in other countries. Being female,
      older age, school location near an industrial site, frequent consumption of
      smoked foods and lower family income were all associated with higher OH-PAHs
      concentrations. Further cohort studies are needed to confirm the associations
      between potential exposure sources and children's exposure to PAHs, in order to
      provide recommendations to reduce exposure.

PMID- 28454028
TI  - Corrigendum to "Groundwater arsenic contamination in Burkina Faso, West Africa:
      Predicting and verifying regions at risk" [Sci. Total Environ. 584-585 (2017) 958
      970].

PMID- 28454029
TI  - Aerosol contributions at an urban background site in Eastern Mediterranean -
      Potential source regions of PAHs in PM10 mass.
AB  - In this paper, two backward air mass trajectory-based models (Potential Source
      Contribution Function [PSCF] and Concentration Weighted Trajectory [CWT]) were
      combined, aiming to identify sources and factors defining the load of PM in the
      city of Limassol (Cyprus). The study also focused on the determination of
      atmospheric pathways enriching the aerosol phase of four carcinogenic Polycyclic
      Aromatic Hydrocarbons (PAHs): Benzo(a)pyrene (BaP), Benzo(a)anthracene (BaA),
      Benzo(b)fluoranthene (BbF) and Benzo(k)fluoranthene (BkF), in PM10 mass. The
      analysis was performed on a 0.5 degrees .0.5 degrees  resolution grid for the two
      year period 2011-2012. During cold seasons, regional airflows triggered the
      accumulation of locally produced PM2.5, while the impact of dust plumes
      originated from deserts in NE Africa, Syria and the Middle East, was apparent on
      PM2.5 and principally on PMCOARSE levels. On the contrary, within warm seasons,
      weaker dust PMCOARSE contributions were detected in Limassol from areas in Egypt
      and Libya. Raised particulate-phase PAH concentrations in Limassol were clearly
      related to air parcels reaching Cyprus via continental areas. The use of outdated
      technologies for heating and transportation in Turkey and Syria, and fire events
      in central Turkey, are possible sources of exogenous PAHs throughout cold and
      warm period respectively. The influence of clean marine air masses dropped the
      levels of PAH compounds in all seasons.

PMID- 28454030
TI  - Pesticide impact study in the peri-urban horticultural area of Gran La Plata,
      Argentina.
AB  - Vegetable production systems are characterized by intense pesticide use, yet the
      effects on the surrounding environment are largely unknown and need to be
      studied. Given this knowledge gap, the objective of this work is to determine the
      impact of horticulture on a representative watercourse by conducting an
      integrated study of the occurrence and concentration of pesticides in bottom
      sediments and their relation to lethal and sublethal effects on benthic fauna.
      Two sampling campaigns were conducted during seasons of low and high pesticide
      application in five sites along the Carnaval creek, located in the peri-urban
      area of La Plata City (Buenos Aires, Argentina). The samples were tested for 36
      pesticide compounds by GC-MS and LC-MS, and whole-sediment laboratory toxicity
      tests were performed using the native amphipod Hyalella curvispina. The results
      showed a general but variable distribution in the concentrations detected along
      the stream. For each sampling campaign (first/second), the total pesticide loads,
      measured as the sum of herbicides, insecticides and fungicides, were 1080/2329,
      3715/88, and 367/5ngg-1 dw, respectively. Lethal and sublethal effects were
      observed in both sampling campaigns. In order to correlate both sets of results,
      data were assessed by multivariate analysis, including principal component
      analysis. The observed toxicity was considered to be mainly due to insecticides;
      thus, horticultural practices have an impact on nearby watercourses and can
      potentially endanger the benthic fauna. This is the first study in Argentina to
      assess the impact of pesticides on aquatic environments close to horticultural
      production areas.

PMID- 28454031
TI  - Automatic and adaptive paddy rice mapping using Landsat images: Case study in
      Songnen Plain in Northeast China.
AB  - Spatiotemporal explicit information on paddy rice distribution is essential for
      ensuring food security and sustainable environmental management. Paddy rice
      mapping algorithm through the Combined Consideration of Vegetation phenology and
      Surface water variations (CCVS) has been efficiently applied based on the 8day
      composites time series datasets. However, the great challenge for phenology-based
      algorithms introduced by unpromising data availability in middle/high spatial
      resolution imagery, such as frequent cloud cover and coarse temporal resolution,
      remained unsolved. This study addressed this challenge through developing an
      automatic and Adaptive paddy Rice Mapping Method (ARMM) based on the cloud
      frequency and spectral separability. The proposed ARMM method was tested on the
      Landsat 8 Operational Land Imager (OLI) image (path/row 118/028) in the Songnen
      Plain in Northeast China in 2015. First, the whole study region was automatically
      and adaptively subdivided into undisturbed and disturbed regions through a per
      pixel strategy based on Landsat image data availability during key phenological
      stage. Second, image objects were extracted from approximately cloud-free images
      in disturbed and undisturbed regions, respectively. Third, phenological metrics
      and other feature images from individual or multiple images were developed.
      Finally, a flexible automatic paddy rice mapping strategy was implemented. For
      undisturbed region, an object-oriented CCVS method was utilized to take the full
      advantages of phenology-based method. For disturbed region, Random Forest (RF)
      classifier was exploited using training data from CCVS-derived results in
      undisturbed region and feature images adaptively selected with full
      considerations of spectral separability and the spatiotemporal coverage. The ARMM
      method was verified by 473 reference sites, with an overall accuracy of 95.77%
      and kappa index of 0.9107. This study provided an efficient strategy to
      accommodate the challenges of phenology-based approaches through transferring
      knowledge in parts of a satellite scene with finer time series to targets (other
      parts) with deficit data availability.

PMID- 28454032
TI  - Identifying spatial clusters of flood exposure to support decision making in risk
      management.
AB  - A sound understanding of flood risk drivers (hazard, exposure and vulnerability)
      is essential for the effective and efficient implementation of risk-reduction
      strategies. In this paper, we focus on 'exposure' and study the influence of
      different methods and parameters of flood exposure analyses in Switzerland. We
      consider two types of exposure indicators and two different spatial aggregation
      schemes: the density of exposed assets (exposed numbers per km2) and the ratios
      of exposed assets (share of exposed assets compared to total amount of assets in
      a specific region) per municipality and per grid cells of similar size as the
      municipalities. While identifying high densities of exposed assets highlights
      priority areas for cost-efficient strategies, high exposure ratios can suggest
      areas of interest for strategies focused on the most vulnerable regions, i.e.
      regions with a low capacity to cope with a disaster. In Switzerland, the spatial
      distribution of high exposure densities and exposure ratios tend to be
      complementary. With regards to the methods, we find that the spatial cluster
      analysis provides more information for the prioritization of flood protection
      measures than 'simple' maps of spatially aggregated data represented in
      quantiles. In addition, our study shows that the data aggregation scheme
      influences the results. It suggests that the aggregation based on grid cells
      supports the comparability of different regions better than aggregation based on
      municipalities and is, thus, more appropriate for nationwide analyses.

PMID- 28454033
TI  - Comparing current chemical methods to assess biochar organic carbon in a
      Mediterranean agricultural soil amended with two different biochars.

PMID- 28454034
TI  - Immobilization of phenanthrene onto gemini surfactant modified sepiolite at
      solid/aqueous interface: Equilibrium, thermodynamic and kinetic studies.
AB  - The immobilization of phenanthrene from aqueous phase onto natural and gemini
      surfactant modified sepiolite was investigated with respect to contact time, pH,
      ionic strength and temperature. The surface modification was examined through FT
      IR characterization, SEM technique, and the thermogravimetric analysis. The
      maximum sorption capacity of phenanthrene on modified sepiolite was 95.15MUgg-1
      with initial PHE concentration 1.0mgL-1, temperature 293K, pH7, and ionic
      strength 1M. The corresponding PHE removal efficiency was higher than 95%. The
      Langmuir, Freundlich and Temkin isotherm models were applied to describe the
      phenanthrene sorption behavior and the Freundlich equation agreed well with the
      experimental data. The evaluation of the thermodynamic parameters indicated that
      the immobilization of phenanthrene onto gemini surfactant modified sepiolite was
      a spontaneous and exothermic process from 283 to 313K. The pseudo-first-order,
      pseudo-second-order, Elovich, and intraparticle diffusion models were used to
      evaluate the kinetic data. According to the calculated kinetic parameters, the
      immobilization process of phenanthrene followed the Elovich kinetic model with
      the highest correlation coefficients. The obtained results show that gemini
      surfactant modified sepiolite could be effectively utilized as one type of low
      cost clay material to remove polycyclic aromatic hydrocarbons from water
      effluents.

PMID- 28454035
TI  - Occurrence and genetic diversity of Cryptosporidium and Giardia in urban
      wastewater treatment plants in north-eastern Spain.
AB  - This study was designed to investigate the presence and removal efficiency of
      Cryptosporidium and Giardia in wastewater treatment plants at the 20 most
      populated towns in Aragon (north-eastern Spain). Samples of influent and effluent
      wastewater and dewatered sewage sludge were collected seasonally from 23 plants
      and processed according to USEPA Method 1623. All samples from raw and treated
      wastewater tested positive for Giardia, at an average concentration of 3247+/
      2039cysts/l and 50+/-28cysts/l, respectively. Cryptosporidium was identified in
      most samples from both raw (85/92) and treated (78/92) wastewaters in a
      concentration significantly lower than Giardia, at both influent (96+/
      105oocysts/l) and effluent samples (31+/-70oocysts/l) (P<0.001). The (oo)cyst
      counts peaked in summer in most plants. The removal efficiency was higher for
      Giardia (1.06-log to 2.34-log) than Cryptosporidium (0.35-log to 1.8-log).
      Overall, high removal efficiency values were found for Giardia after secondary
      treatment based on activated sludge, while tertiary treatment (microfiltration,
      chlorination and/or ultraviolet irradiation) was needed to achieve the greatest
      removal or inactivation of Cryptosporidium. Most samples of treated sludge were
      positive for Giardia (92/92) and Cryptosporidium (45/92), at an average
      concentration of 20-593cysts/g and 2-44oocyst/g, respectively. The molecular
      characterization of Cryptosporidium oocysts and Giardia cysts were attempted at
      the SSU rRNA/GP60 and bg/tpi loci, respectively. G. duodenalis sub-assemblage AII
      was identified in all plants, with a large proportion of samples (15/47)
      harboring mixed assemblages (AII+B). Nine Cryptosporidium species and six
      subtypes were identified, with C. parvum IIaA15G2R1 being the most prevalent. The
      presence of significant numbers of (oo)cysts in samples of final effluents and
      treated sludge reveals the limited efficacy of conventional treatments in
      removing (oo)cysts and highlights the potential environmental impact and public
      health risks associated with disposal and reclamation of wastewater.

PMID- 28454036
TI  - A clean environmental week: Let the nature breathe.
AB  - High levels of CO2 emissions in the atmosphere and toxic pollutants in air, water
      and food have serious repercussions on all life's systems, including living
      beings, environment and economy. Everyone on the Earth is concerned by pollution
      in some way or another, no matter where and how the pollution is produced as
      airborne and foodborne pollutants could circulate around the world in different
      ways, through for example climate components (wind, rain) and/or import and
      export of foodstuffs. Similarly to living beings that take advantage of day-night
      circadian rhythms to recover after diurnal hardships, the environment in its
      entirety could also be seen as a complex living system that needs regular breaks
      to assimilate or ingest toxic pollutants produced during intensive and continuous
      industrial processes. If greenhouses gas emissions and pollution rates continue
      to increase at the same rates as they are nowadays, uncontrollable climate
      effects might be inevitable and the air quality in some crowded cities in the
      world might be hardly respirable in the future. A global "Clean Environmental
      Week" is discussed as an attempt toward reducing air pollution and CO2 emissions
      through the interruption or reduction of industrial polluting activities
      regularly, for a week or so per year, to let the nature 'breathe' and recover
      from environmentally challenging pollutions. A clean environmental period of 10
      days per year could reduce CO2 emissions by about one billion tons of CO2 per
      annum.

PMID- 28454037
TI  - Agricultural expansion as risk to endangered wildlife: Pesticide exposure in wild
      chimpanzees and baboons displaying facial dysplasia.
AB  - Prenatal exposure to environmental endocrine disruptors can affect development
      and induce irreversible abnormalities in both humans and wildlife. The northern
      part of Kibale National Park, a mid-altitude rainforest in western Uganda, is
      largely surrounded by industrial tea plantations and wildlife using this area
      (Sebitoli) must cope with proximity to human populations and their activities.
      The chimpanzees and baboons in this area raid crops (primarily maize) in
      neighboring gardens. Sixteen young individuals of the 66 chimpanzees monitored
      (25%) exhibit abnormalities including reduced nostrils, cleft lip, limb
      deformities, reproductive problems and hypopigmentation. Each pathology could
      have a congenital component, potentially exacerbated by environmental factors. In
      addition, at least six of 35 photographed baboons from a Sebitoli troop (17%)
      have similar severe nasal deformities. Our inquiries in villages and tea
      factories near Sebitoli revealed use of eight pesticides (glyphosate,
      cypermethrin, profenofos, mancozeb, metalaxyl, dimethoate, chlorpyrifos and 2,4-D
      amine). Chemical analysis of samples collected from 2014 to 2016 showed that mean
      levels of pesticides in fresh maize stems and seeds, soils, and river sediments
      in the vicinity of the chimpanzee territory exceed recommended limits. Notably,
      excess levels were found for total DDT and its metabolite pp'-DDE and for
      chlorpyrifos in fresh maize seeds and in fish from Sebitoli. Imidacloprid was
      detected in coated maize seeds planted at the edge the forest and in fish samples
      from the Sebitoli area, while no pesticides were detected in fish from central
      park areas. Since some of these pesticides are thyroid hormone disruptors, we
      postulate that excessive pesticide use in the Sebitoli area may contribute to
      facial dysplasia in chimpanzees and baboons through this endocrine pathway.
      Chimpanzees are considered as endangered by IUCN and besides their intrinsic
      value and status as closely related to humans, they have major economic value in
      Uganda via ecotourism. Identifying and limiting potential threats to their
      survival such be a conservation priority.

PMID- 28454038
TI  - Long term variations measurement of electromagnetic field exposures in Alcala de
      Henares (Spain).
AB  - Electromagnetic radiowave exposure is a major concern in most countries due to
      possible adverse health effects. Over the last 10years, many technological
      changes (digital television, mobile technologies, wireless networks...) have led
      to variations in the electromagnetic field (EMF) levels. A large number of
      studies devoted to the analysis of EMF levels with personal dosimeters or
      computer models of the exposure of mobile stations have been conducted. However,
      the study of the exposure values, taking into account all the existing sources,
      and their evolution in a wide area, using measurements, has rarely been
      performed. In this paper, we provide a comparison of the EMF exposure levels for
      the city of Alcala de Henares (Spain) over a ten-year period using a broadband
      isotropic probe in the range from 100kHz to 3GHz. A statistical and spatial
      analysis of the measurements and their variations are also presented for the
      study of the global and local variations. The measured values in the period from
      2006 to 2015 were ranging from 0.02 to 2.05V/m. Our global results show a
      moderate increase from 2006 to 2010 and they are almost invariant from 2010 to
      2015. Although the whole dataset does not have relevant statistical difference,
      we have found marked local differences. In the city areas where the population
      density has remained unaltered, we have measured lower exposure levels.
      Conversely, new urban and industrial developments have demanded new resources,
      which have potentially contributed to the observed increase in the measured
      electric field levels within these areas.

PMID- 28454039
TI  - Land cover change during a period of extensive landscape restoration in Ningxia
      Hui Autonomous Region, China.
AB  - Environmental change has been a topic of great interest over the last century due
      to its potential impact on ecosystem services that are fundamental for
      sustainable development and human well-being. Here, we assess and quantify the
      spatial and temporal variation in land cover in Ningxia Hui Autonomous Region
      (NHAR), China. With high-resolution (30m) imagery from Landsat 4/5-TM and 8-OLI
      for the entire region, land cover maps of the region were created to explore
      local land cover changes in a spatially explicit way. The results suggest that
      land cover changes observed in NHAR from 1991 to 2015 reflect the main goals of a
      national policy implemented there to recover degraded landscapes. Forest,
      herbaceous vegetation and cultivated land increased by approximately 410,200ha,
      708,600ha and 164,300ha, respectively. The largest relative land cover change
      over the entire study period was the increase in forestland. Forest growth
      resulted mainly from the conversion of herbaceous vegetation (53.8%) and
      cultivated land (30.8%). Accurate information on the local patterns of land cover
      in NHAR may contribute to the future establishment of better landscape policies
      for ecosystem management and protection. Spatially explicit information on land
      cover change may also help decision makers to understand and respond
      appropriately to emerging environmental risks for the local population.

PMID- 28454040
TI  - The role of dissimilatory arsenate reducing bacteria in the biogeochemical cycle
      of arsenic based on the physiological and functional analysis of Aeromonas sp.
      O23A.
AB  - Dissimilatory arsenate reducing bacteria (DARB) are known to contribute to the
      mobilization of arsenic and other elements from minerals. Despite this, metabolic
      capabilities of only a few DARB strains have been thoroughly investigated so far,
      and the influence of these bacteria on the bioavailability of arsenic in the
      environment is still a topic for discussion. In this study, Aeromonas sp. O23A,
      one of the dominant DARB strains found in the Zloty Stok mine (SW Poland), was
      subjected to a detailed physiological and functional analysis aimed to identify
      the actual environmental impact of this strain. Physiological analyses revealed
      that O23A is a facultative anaerobe, capable of utilizing arsenate as a
      respiratory substrate and acetate, citrate and lactate as electron donors.
      Arsenate reduction was observed within the first 24h of culturing. The strain
      shows high resistance to arsenic and several other heavy metals (i.a. Cu, Fe, Ni
      and Zn) as well tolerance to a broad range of physico-chemical conditions.
      Metabolic preferences of O23A were thoroughly investigated using BiologTM
      MicroArray assay. The strain was found to produce hydroxamate siderophores,
      potentially involved in the mobilization of iron and co-occurring heavy metals
      from minerals. On the other hand, O23A showed high adherence abilities, and its
      involvement in biofilm formation may lead to the entrapment of dissolved arsenic
      species and other toxic ions. The results shed light on the importance of arsenic
      respiration and resistance in the overall metabolism of Aeromonas sp. O23A and
      confirmed its key role in the biogeochemical cycle of arsenic, also in the
      context of self-purification of heavy-metal-contaminated waters.

PMID- 28454041
TI  - Long-term intake of a high-protein diet increases liver triacylglycerol
      deposition pathways and hepatic signs of injury in rats.
AB  - Intake of high-protein (HP) diets has increased over the last years, mainly due
      to their popularity for body weight control. Liver is the main organ handling
      ingested macronutrients and it is associated with the beginning of different
      pathologies. We aimed to deepen our knowledge on molecular pathways affected by
      long-term intake of an HP diet. We performed a transcriptome analysis on liver of
      rats chronically fed with a casein-rich HP diet and analyzed molecular parameters
      related to liver injury. Chronic increase in the dietary protein/carbohydrate
      ratio up-regulated processes related with amino acid uptake/metabolism and lipid
      synthesis, promoting a molecular environment indicative of hepatic
      triacylglycerol (TG) deposition. Moreover, changes in expression of genes
      involved in acid-base maintenance and oxidative stress indicate alterations in
      the pH balance due to the high acid load of the diet, which has been linked to
      liver/health damage. Up-regulation of immune-related genes was also observed. In
      concordance with changes at gene expression level, we observed increased liver TG
      content and increased serum markers of hepatic injury/inflammation (aspartate
      transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly
      increased hepatic mRNA and protein levels of HSP90, a marker of liver injury.
      Thus, we show for the first time that long-term consumption of an HP diet,
      resulting in a high acid load, results in a hepatic transcriptome signature
      reflecting increased TG deposition and increased signs of health risk (increased
      inflammation, alterations in the acid-base equilibrium and oxidative stress).
      Persistence of this altered metabolic status could have unhealthy consequences.

PMID- 28454042
TI  - Cortical plasticity and levodopa-induced dyskinesias in Parkinson's disease:
      Connecting the dots in a multicomponent network.
AB  - Levodopa-induced dyskinesias are motor complications following long term
      dopaminergic therapy in Parkinson's disease (PD). Impaired brain plasticity
      resulting in the creation of aberrant motor maps intended to encode normal
      voluntary movement is proposed to result in the development of dyskinesias.
      Traditionally, the various nodes in the motor network like the striato-cortical
      and the cerebello-thalamic loops were thought to function independent of each
      other with little communication among them. Anatomical evidence from primates
      revealed the existence of reciprocal loops between the basal ganglia and the
      cerebellum providing an anatomical basis for communication between the motor
      network loops. Dyskinetic PD patients reveal impaired brain plasticity within the
      motor cortex which may be modulated by cortico-cortical, cerebello-cortical or
      striato-cortical connections. In this article, we review the evidence for altered
      plasticity in the multicomponent motor network in the context of levodopa induced
      dyskinesias in PD. Current evidence suggests a pivotal role for the cerebellum in
      the larger motor network with the ability to integrate sensorimotor information
      and independently influence multiple nodes in this network. Targeting the
      cerebellum seems to be a justified approach for future interventions aimed at
      attenuating levodopa-induced dyskinesias.

PMID- 28454043
TI  - Vacuum scanning capillary photoemission microscopy.
AB  - We demonstrate the use of a conical capillary in a scanning probe microscopy for
      surface analysis. The probe can measure photoemission from a substrate by
      transmitting photoelectrons along the capillary as a function of probe position.
      The technique is demonstrated on a model substrate consisting of a gold
      reflecting layer on a compact disc which has been illuminated by an unfocused
      laser beam with a wavelength 400nm, from a femtosecond laser with a beam size of
      4mm. A quartz capillary with a 2-um aperture has been used in the experiments.
      The period of gold microstructure, shown to be 1.6u, was measured by the conical
      probe operating in shear force mode. In shear force regime, the dielectric
      capillary has been used as a "classical" SPM tip, which provided images
      reflecting the surface topology. In a photoelectron regime photoelectrons passed
      through hollow tip and entered a detector. The spatial distribution of the
      recorded photoelectrons consisted of periodic mountain-valley strips, resembling
      the surface profile of the sample. Submicron spatial resolution has been
      achieved. This approach paves the way to study pulsed photodesorption of large
      organic molecular ions with high spatial and element resolution using the
      combination of a hollow-tip scanner with time-of-flight technique.

PMID- 28454045
TI  - Canadian harm reduction policies: A comparative content analysis of provincial
      and territorial documents, 2000-2015.
AB  - BACKGROUND: Access to harm reduction interventions among substance users across
      Canada is highly variable, and largely within the policy jurisdiction of the
      provinces and territories. This study systematically described variation in
      policy frameworks guiding harm reduction services among Canadian provinces and
      territories as part of the first national multimethod case study of harm
      reduction policy. METHODS: Systematic and purposive searches identified publicly
      accessible policy texts guiding planning and organization of one or more of seven
      targeted harm reduction services: needle distribution, naloxone, supervised
      injection/consumption, low-threshold opioid substitution (or maintenance)
      treatment, buprenorphine/naloxone (suboxone), drug checking, and safer inhalation
      kits. A corpus of 101 documents written or commissioned by provincial/territorial
      governments or their regional health authorities from 2000 to 2015 were
      identified and verified for relevance by a National Reference Committee. Texts
      were content analyzed using an a priori governance framework assessing managerial
      roles and functions, structures, interventions endorsed, client characteristics,
      and environmental variables. RESULTS: Nationally, few (12%) of the documents were
      written to expressly guide harm reduction services or resources as their primary
      named purpose; most documents included harm reduction as a component of broader
      addiction and/or mental health strategies (43%) or blood-borne pathogen
      strategies (43%). Most documents (72%) identified roles and responsibilities of
      health service providers, but fewer declared how services would be funded (56%),
      specified a policy timeline (38%), referenced supporting legislation (26%), or
      received endorsement from elected members of government (16%). Nonspecific
      references to 'harm reduction' appeared an average of 12.8 times per document-far
      more frequently than references to specific harm reduction interventions (needle
      distribution=4.6 times/document; supervised injection service=1.4
      times/document). Low-threshold opioid substitution, safer inhalation kits, drug
      checking, and buprenorphine/naloxone were virtually unmentioned. Two cases
      (Quebec and BC) produced about half of all policy documents, while 6 cases -
      covering parts of Atlantic and Northern Canada - each produced three or fewer.
      CONCLUSION: Canada exhibited wide regional variation in policies guiding the
      planning and organization of Canadian harm reduction services, with some areas of
      the country producing few or no policies. Despite a wealth of effectiveness and
      health economic research demonstrating the value of specific harm reduction
      interventions, policies guiding Canada from 2000 to 2015 did not stake out harm
      reduction interventions as a distinct, legitimate health service domain.

PMID- 28454044
TI  - Unintended impacts of regulatory changes to British Columbia Methadone
      Maintenance Program on addiction and HIV-related outcomes: An interrupted time
      series analysis.
AB  - BACKGROUND: In February 2014, several regulatory reforms were introduced to the
      methadone maintenance treatment (MMT) program in British Columbia, Canada,
      including a switch to a ten-times more concentrated methadone formulation and
      restrictions in pharmacy delivery services. We evaluated possible unintended
      effects of these changes on illicit drug use patterns and HIV treatment outcomes
      among HIV-positive opioid users. METHODS: Data was drawn from ACCESS, a
      prospective community-recruited cohort of HIV-positive people who use illicit
      drugs in Vancouver, Canada. Interrupted Time Series Analyses were used to
      evaluate impacts of the policy change on monthly rates of MMT enrolment, illicit
      heroin injection, antiretroviral therapy (ART) adherence, and HIV viral
      suppression among HIV-positive opioid users between November 2012 and May 2015.
      RESULTS: A total of 331 HIV-positive opioid users were included. The MMT policy
      change led to a significant immediate 11.5% increase in heroin injection, and
      15.9% drop in optimal ART adherence. A gradual increase in the prevalence of MMT
      enrolment after the policy change was also documented (0.9% per month). No
      changes in viral suppression rates were observed. CONCLUSION: We observed
      immediate increases in illicit heroin injection and decreases in ART adherence in
      the wake of regulatory changes to the local MMT program. These findings
      underscore the need to consider potential unintended effects of altering health
      programmes for vulnerable populations, the need to develop appropriate mitigation
      strategies, as well as to involve all relevant stakeholders in the planning and
      implementations of new policies.

PMID- 28454046
TI  - Preliminary investigation of catalytic, antioxidant, anticancer and bactericidal
      activity of green synthesized silver and gold nanoparticles using Actinidia
      deliciosa.
AB  - Herein we report a rapid low cost one step green synthetic method using Actinidia
      deliciosa fruit extract for preparation of stable and multifunctional silver and
      gold nanoparticles. The synthesized nanoparticles were successfully used as green
      catalysts for the reduction of 4-nitrophenol (4-NP) and methylene blue (MB). The
      enhanced biological activity of the prepared nanoparticles was investigated based
      on its highly stable antioxidant, anticancer and bactericidal effects. TEM
      micrographs showed that the silver nanoparticles (AgNPs) formed were
      predominantly spherical in shape having diameters ranging from 25 to 40nm, while
      gold nanoparticles (AuNPs) shown particle size ranges from 7 to 20nm. EDAX
      (energy-dispersive X-ray spectroscopy) and XPS (X-ray photoelectron spectroscopy)
      results confirmed the presence of elemental silver and gold. X-ray diffraction
      (XRD) pattern revealed the formation of face-centered cubic structure for AgNPs
      and AuNPs. The Fourier-transform infrared (FTIR) spectrum indicated the presence
      of possible functional groups in the biomolecule responsible for capping the
      nanoparticles. The AgNPs treated HCT116 cells showed 78% viability at highest
      concentration (350MUg/mL), while AuNPs showed 71% viability at highest
      concentration (350MUg/mL) using MTT assay, which provides promising approach for
      alternative nano-drug development. The antimicrobial activity of the
      nanoparticles was investigated using Pseudomonas aeruginosa (P.aeruginosa) in
      which damaging the cell membrane was observed by TEM images. Our results revealed
      that the green synthesis method is easy, rapid, inexpensive, eco-friendly and
      efficient in developing multifunctional nanoparticles in near future in the field
      of biomedicine, water treatment and nanobiotechnology.

PMID- 28454047
TI  - Use of light emitting diodes (LEDs) for enhanced lipid production in micro-algae
      based biofuels.
AB  - Microalgae are an alternative source for renewable energy to overcome the energy
      crises caused by exhaustion of fuel reserves. Algal biofuel technology demands a
      cost effective strategy for net profitable productivity. Inconsistent
      illumination intensities hinder microalgal growth. The light-utilizing efficiency
      of the cells is critical. Light scarcity leads to low production and high
      intensities cause photo-inhibition. We report effective usage of LEDs of
      different band wavelengths on the growth of microalgae in a closed, controlled
      environment to generate biomass and lipid yields. Among the different intensity
      and wavelengths tested. The light intensities of 500lx of blue-red combination
      gave maximum biomass in terms of cell density. LED of red light 220lx wavelength
      doubled the lipid dry weight from 30% (w/w) in white light to 60% (w/w). Thin
      layer lipid chromatogram demonstrated a dense and prominent spot of
      triacylglycerols in the red light, 220lx grown cultures. The FTIR profile
      indicates that different wavelength exposure did not alter the functional groups
      or change the chemical composition of the extracted lipids ensuring the quality
      of the product. We reiterate the fact that combination of red and blue LEDs is
      favoured over white light illumination for generation of biomass. In addition, we
      report an exciting finding of exposure to LEDs of red wavelength post-biomass
      generation lead to enhanced lipid production. This simple process doubled the
      lipid content harvested in 20days culture period.

PMID- 28454048
TI  - Antibacterial activity of biochemically capped iron oxide nanoparticles: A view
      towards green chemistry.
AB  - A green approach to fabricate nanoparticles has been evolved as a revolutionary
      discipline. Eco-compatible reaction set ups, use of non-toxic materials and
      production of highly active biological and photocatalytic products are few
      benefits of this greener approach. Here, we introduce a green method to
      synthesize Fe oxide NPs using Punica granatum peel extract. The formation of Fe
      oxide NPs was optimized using different concentrations of peel extract (20mL,
      40mL and 60mL) to achieve small size and better morphology. The results indicate
      that the FeNPs, obtained using 40mL concentration of peel extract possess the
      smallest size. The morphology, size and crystallinity of NPs was confirmed by
      implementing various techniques i.e. UV-Vis spectroscopy, X-ray diffraction,
      Scanning Electron Microscopy and Electron Diffraction Spectroscopy. The bio
      chemicals responsible for reduction and stabilization of FeNPs were confirmed by
      FT-IR analysis. The biogenic FeNPs were tested for their size dependent
      antibacterial activity. The biogenic FeNPs prepared in 40mL extract
      concentrations exhibited strongest antibacterial activity against Pseudomonas
      aeruginosa i.e. 22 (+/-0.5) mm than FeNPs with 20mL and 60mL extract
      concentrations i.e. 18 (+/-0.4) mm and 14 (+/-0.3) mm respectively. The optimized
      FeNPs with 40mL peel extract are not only highly active for ROS generation but
      also show no hemolytic activity. Thus, FeNPs synthesized using the greener
      approach are found to have high antibacterial activity along with
      biocompatibility. This high antibacterial activity can be referred to small size
      and large surface area.

PMID- 28454049
TI  - Response surface method optimization of a novel Hypericin formulation in P123
      micelles for colorectal cancer and antimicrobial photodynamic therapy.
AB  - The photodynamic properties of Hypericin (Hyp) may be used as an alternative
      treatment for malignancies of the lower gastrointestinal tract and for the
      prevention of surgical-site infection; however, its use in photodynamic therapy
      has been limited because of its poor hydrosolubility. Therefore, in order to
      improve its water solubility and its photodynamic effect, Hyp was encapsulated in
      Pluronic P123 (P123) and the photodynamic effects against intestinal and
      epidermal bacteria and against two lineages of intestinal colon carcinoma cells
      were investigated. Two response surface methods (RSM) were used to achieve the
      best in vitro photodynamic activity against Enterococcus faecalis, Escherichia
      coli and Staphylococcus aureus: in the first (full 23 RSM), Hyp concentration
      (HC*), incubation time (IT*) and LED-light time (LT*) were considered as the
      independent variables and E. faecalis inhibition as the dependent variable. In
      the second (full 32 RSM), Hyp concentration (HC*) and P123 concentration (CC*)
      were considered as independent variables and E. faecalis, E. coli and S. aureus
      inhibition as dependent variables. The optimized experimental conditions achieved
      were: Hyp concentration=37.5MUmol/L; P123 concentration=21.5 MUmol/L and
      6.3J/cm2, which resulted in 2.86+/-0.12 and 2.30+/-0.31CFU log-reductions of E.
      faecalis and S. aureus. No effect was seen against E. coli. The cytotoxic effects
      of Hyp/P123 were also investigated for Caco-2 and HT-29 intestinal colon
      carcinoma cells at Hyp/P123 concentrations of 1, 0.5, 0.25 and 0.1MUmol/L for
      Caco-2 cells and 4, 3, 2 and 1MUmol/L for HT-29 cells. The cytotoxic
      concentrations for 50% (CC50) and 90% (CC90) of Hyp/P123 were 0.443 and
      0.870MUmol/L for Caco-2 cells and 1.4 and 2.84MUmol/L for HT-29 cells. The P123
      nanocarrier played a significant role in the permeation of Hyp through the cell
      membrane leading to significant cell death, and showed itself to be a promising
      photosensitizer for PDT that could be suitable for the treatment of colonic
      diseases since it is effective against positive Gram bacteria and intestinal
      colon carcinoma cells.

PMID- 28454050
TI  - Forensic genetic analyses in isolated populations with examples of central
      European Valachs and Roma.
AB  - Isolated populations present a constant threat to the correctness of forensic
      genetic casework. In this review article we present several examples of how
      analyzing samples from isolated populations can bias the results of the forensic
      statistics and analyses. We select our examples from isolated populations from
      central and southeastern Europe, namely the Valachs and the European Roma. We
      also provide the reader with general strategies and principles to improve the
      laboratory practice (best practice) and reporting of samples from supposedly
      isolated populations. These include reporting the precise population data used
      for computing the forensic statistics, using the appropriate theta correction
      factor for calculating allele frequencies, typing ancestry informative markers in
      samples of unknown or uncertain ethnicity and establishing ethnic-specific
      forensic databases.

PMID- 28454051
TI  - No association between SLC6A2, SLC6A3, DRD2 polymorphisms and schizophrenia in
      the Han Chinese population.
AB  - This study was intended to ascertain whether SNPs in dopaminergic and
      serotoninergic pathway genes SLC6A2, SLC6A3 and DRD2 are associated with
      schizophrenia in Han Chinese people. We conducted a case-control study by
      genotyping 7 SNPs of the three genes in 1034 schizophrenia patients and 1034
      controls. No significant difference in the allelic or genotypic frequency was
      detected between cases and controls despite one positive haplotype (rs1362621
      rs2242446-rs5564). Stratified analysis of gender and gene-gene interaction
      analysis showed no positive results. In summary, our study denies the major role
      of these SNPs within the three genes for schizophrenia in Han Chinese.

PMID- 28454052
TI  - A multi-biomarker approach in scallop Chlamys farreri to assess the impact of
      contaminants in Qingdao coastal area of China.
AB  - A multi-biomarker approach was carried out to classify the environmental quality
      and the adverse effects of contaminants on scallop Chlamys farreri. The scallops
      were collected from three sampling stations in Qingdao coastal area of China in
      March, May, August and October of 2015. A suite of environmental factors and
      biomarkers, including temperature, salinity, pH, the concentrations of polycyclic
      aromatic hydrocarbons (PAHs), tetrabromobisphenol A (TBBPA) and metals (Cr, Mn,
      Cu, Zn, Cd, Pb, As) in seawater and soft tissue, mRNA expression of aryl
      hydrocarbon receptor (AhR) and P-glycoprotein (P-gp), 7-ethoxyresorufin O
      deethylase (EROD), glutathione-S-transferase (GST), uridine-diphosphate
      glucuronyl-transferase (UGT), sulfotransferase (SULT), metallothionein (MT),
      Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), lipid
      peroxidation (LPO) and protein carbonyl (PC) contents and DNA strand breaks, were
      measured in the gill and digestive gland. The results showed that S2 was the most
      polluted while S1 was identified the least polluted. Despite the differentiation
      of pollution levels and environmental parameters the selected biomarkers
      responded efficiently to contaminants. Principal component analysis (PCA)
      revealed that EROD for PAHs, AhR for TBBPA, MT for Cr, Pb and Mn, LPO and PC for
      Zn were the effective biomarkers respectively. This study demonstrated that the
      application of multi-biomarker approach in conjunction with the traditional
      analysis of environmental parameters and contaminants provided valuable
      information in environmental risk assessment.

PMID- 28454053
TI  - Source identification and exchangeability of heavy metals accumulated in
      vegetable soils in the coastal plain of eastern Zhejiang province, China.
AB  - Vegetable production in China is suffering increasingly heavy metal damages from
      various pollution sources including agricultural, industrial and other
      activities. It is of practical significance to understand the effects of human
      activities on the accumulation and exchangeability of soil heavy metals in
      vegetable fields. In this study, seventy-two arable layer samples of vegetable
      soils were collected from the Shaoxing coastal plain, a representative region of
      the coastal plain of eastern Zhejiang province, China for characterizing the
      effects of fertilization methods on accumulation and exchangeable heavy metals in
      soils (Exchangeable heavy metals in the soil samples were extracted by 0.01molL-1
      CaCl2). The different origins of heavy metals in the vegetable soils were
      investigated by multivariate statistical techniques, including principal
      component analysis (PCA) and cluster analysis (CA). Marked increases were noted
      for soil heavy metals due to long-term manure or chemical fertilizer application.
      Three significant components were extracted by PCA, explaining 78.86% of total
      variance. Mn, Co, Ni, Fe, and Al were associated in lithogenic components, while
      an anthropogenic origin was identified for Cu, Cr, Pb, Zn, Cd, Hg. However, As
      level was due to the geochemical background and was not linked to soil
      management. The results obtained by cluster analysis elucidated individual
      relationships between metals and agreed with PCA. Cu, Cr, Pb, and Zn in the soils
      that were mainly associated with the application of chemical fertilizers, organic
      manures or other activities regarding soil management. Although the origin of Cd,
      Hg, and As was also attributed to soil management, other sources like vehicle
      exhaust or aerial depositions were not discarded as possible contributors. Soil
      amended with organic fertilizer contained more Cu, Pb, Zn and Cr; whereas the
      soil amended with chemical fertilizer had more Cd. Application of fertilizers
      also had significant effect on the concentrations of exchangeable heavy metals.
      Higher mean concentrations of exchangeable Cd and Pb were found in the soils
      amended with chemical fertilizers, while those of exchangeable Cu and Zn were
      found in the soils amended with organic fertilizers.

PMID- 28454054
TI  - 1H NMR-based metabolomics investigation on the effects of petrochemical
      contamination in posterior adductor muscles of caged mussel Mytilus
      galloprovincialis.
AB  - Environmental metabolomics is a high-throughout approach that provides a snapshot
      of the metabolic status of an organism. In order to elucidate the biological
      effects of petrochemical contamination on aquatic invertebrates, mussels Mytilus
      galloprovincialis were caged at the "Augusta-Melilli-Priolo" petrochemical area
      and Brucoli (Sicily, south Italy), chosen as the reference site. After confirming
      the elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and
      mercury (Hg) in Augusta sediments in our previous work (Maisano et al., 2016a),
      herein an environmental metabolomics approach based on protonic nuclear magnetic
      resonance (1H NMR), coupled with chemometrics, was applied on the mussel
      posterior adductor muscle (PAM), the main muscular system in bivalve molluscs.
      Amino acids, osmolytes, energy storage compounds, tricarboxylic acid cycle
      intermediates, and nucleotides, were found in PAM NMR spectra. Principal
      Component Analysis (PCA) indicated that mussels caged at the polluted site
      clustered separately from mussels from the control area, suggesting a clear
      differentiation between their metabolic profiles. Specifically, disorders in
      energy metabolism, alterations in amino acids metabolism, and disturbance in the
      osmoregulatory processes were observed in mussel PAM. Overall, findings from this
      work demonstrated the usefulness of applying an active biomonitoring strategy for
      environmental risk assessment, and the effectiveness of metabolomics in
      elucidating changes in metabolic pathways of aquatic organisms caged at sites
      differentially contaminated, and thus its suitability to be applied in
      ecotoxicological studies.

PMID- 28454055
TI  - Evaluation of a commercially available radioimmunoassay and enzyme immunoassay
      for the analysis of progesterone and estradiol and the comparison of two
      extraction efficiency methods.
AB  - The measurement of progesterone (P4) and estradiol (E2) is essential for
      monitoring reproductive cycles and can aid in diagnosing the cause of poor
      reproductive performance in dairy cattle. Readily available, reproducible,
      accurate, non-radioactive assays are needed for the assessment of P4 and E2 in
      bovine serum. The gold standard for hormone assessment, radioimmunoassay (RIA),
      was compared with enzyme-linked immunoassay (EIA). Serum collected from various
      points in the estrous cycle was extracted with radiolabeled P4 (ie, 3H-P4; HE)
      and without 3H-P4 (CE) before being used in the assay. For the assessment of P4,
      there is a great degree of correlation between the RIA and EIA (adjusted R-square
      = 0.95; Pearson correlation coefficient (PCC) = 0.98, P < 0.001). A difference
      between the RIA and EIA methods was not detected for E2 concentrations (P =
      0.16), but the correlation between techniques was poor (adjusted R-squared =
      0.73; PCC = 0.87, P = 0.002). There was no difference in the serum extraction
      efficiency as measured with 3H-P4 as opposed to without (P = 0.94). The two
      methods for the measurement of serum extraction efficiency were highly correlated
      (adjusted R-square = 0.83; PCC = 0.92, P < 0.001). The concordance correlation
      coefficient (CCC) showed an excellent agreement between RIA and EIA for P4
      determination (0.89) and between HE and CE methods (0.90). Although the 95%
      limits of agreement of the Bland-Altman plots encompassed 89% (8/9) and 92%
      (12/13) of the differences between methods for P4 quantification and extraction
      respectively, the CCC indicated an excellent agreement among them. The CCC
      between RIA and EIA for E2 quantification was 0.68 which corresponds with a fair
      agreement; however, the 95% limits of agreement of the Bland-Altman plot
      encompassed 100% (9/9) of differences between methods. The EIA and CE methods are
      comparable alternatives to the RIA and HE methods, respectively and can be used
      to quantify P4 and E2 for bovine serum.

PMID- 28454056
TI  - Dialkyl anionic surfactant in field-amplified sample injection and sweeping
      micellar electrokinetic chromatography for determination of eight leanness
      promoting beta-agonists in animal feeds.
AB  - The beta-adrenergic agonists (beta-agonists) working as repartitioning agents
      that make the carcass leaner and enhance the feeding efficiency in animals have
      been banned in the European Union, China and Taiwan. Here, traditional anionic
      surfactants, such as sodium dodecyl sulfate (SDS) were replaced with sodium di-(2
      ethylhexyl)-sulfosuccinate (AOT) in field-amplified sample injection and sweeping
      micellar electrokinetic chromatography (FASI-sweeping MEKC) for simultaneous
      analysis of eight beta-agonists in animal feeds. The AOT vesicles provided a
      better resolution of beta-agonists than micelles of SDS. The detection limits of
      the eight beta-agonists were above 5ng/mL by using this stacking capillary
      electrophoresis (CE) method. In comparison of traditional MEKC method (sample
      injection, 1psi for 5s), the stacking strategy provided 400-2000 fold sensitivity
      enhancement. After method validation, this method was successfully applied for
      analyzing four animal feeds, and none beta-agonist was detected. This strategy
      possessing good resolution of eight beta-agonists was suitable for serving as a
      tool for routine analysis of animal feeds.

PMID- 28454057
TI  - Application of 2D-NMR with room temperature NMR probes for the assessment of the
      higher order structure of filgrastim.
AB  - The higher order structure (HOS) of biotherapeutics is a critical quality
      attribute that can be evaluated by nuclear magnetic resonance (NMR) spectroscopy
      at atomic resolution. NMR spectral mapping of HOS can be used to establish HOS
      consistency of a biologic across manufacturing changes or to compare a biosimilar
      to an innovator reference product. A previous inter-laboratory study performed
      using filgrastim drug products demonstrated that two-dimensional (2D)-NMR 1HN
      15NH heteronuclear correlation spectroscopy is a highly robust and precise method
      for mapping the HOS of biologic drugs at natural abundance using high sensitivity
      NMR 'cold probes.' Here, the applicability of the 2D-NMR method to fingerprint
      the HOS of filgrastim products is demonstrated using lower sensitivity, room
      temperature NMR probes. Combined chemical shift deviation and principal component
      analysis are used to illustrate the performance and inter-laboratory precision of
      the 2D-NMR method when implemented on room temperature probes.

PMID- 28454058
TI  - Identification and characterization of process-related substances and degradation
      products in apremilast: Process optimization and degradation pathway elucidation.
AB  - This study aims at investigating the separation, identification and
      characterization of related substances in apremilast by LC-MS hyphenated
      techniques, as well as the synthesis optimization and the degradation pathways
      elucidation. Forced degradation studies were conducted under the ICH prescribed
      stress conditions. The chromatographic separation was achieved on XBridge C18
      column (4.6mm*150mm, 3.5MUm) using a mobile phase consisting of water adjusted to
      pH 3.0 with formic acid as solvent A and acetonitrile as solvent B in linear
      gradient elution program. Twelve related substances were detected all together in
      apremilast and its stress samples. Their structures were identified mainly
      through positive ESI high-resolution TOF-MS analysis of the parent ions' accurate
      masses and elemental compositions, and the corresponding MS/MS spectra
      elucidation. There were three process-related substances and nine degradation
      products, seven of them were first reported. Two degradation products and one
      process-related substance were further verified by semi-preparation and NMR
      determination. Their origins and formation mechanisms were also discussed, based
      on which effective approaches for the synthesis optimization were conducted.
      Therefore, the related substances investigation are valuable for apremilast
      manufacturing process optimization and quality control.

PMID- 28454059
TI  - Outcome-focused judgements of moral dilemmas in schizophrenia.
AB  - Previous research on moral judgement in healthy adults suggests a complex
      interplay of automatic, emotional and deliberative processing. We aimed to
      advance understanding of these processes by examining moral judgement in
      individuals with schizophrenia, a population characterised by social-cognitive
      deficits and interpersonal difficulties. Forty-five patients with schizophrenia
      and 27 healthy controls judged high-conflict moral dilemmas in response to 3rd
      person (i.e. "Is it morally okay to [perform X]?") and 1st-person (i.e. "Would
      you [perform X]?") probes. Controls were less utilitarian for 3rd-person than 1st
      person probes, while this discrepancy did not hold for patients. Utilitarianism
      in patients correlated with higher levels of interpersonal conflict. Findings
      suggest that people with schizophrenia focus equally on outcomes across moral
      judgement conditions that ought normally to elicit an outcome-action discrepancy,
      suggesting that they are less influenced by an automatic aversive response to
      harmful acts in dilemma scenarios, consistent with a dual-process model of moral
      judgement.

PMID- 28454060
TI  - Heated humidified high-flow nasal cannula oxygen after thoracic surgery - A
      randomized prospective clinical pilot trial.
AB  - BACKGROUND: Thoracic surgery patients are at high-risk for adverse pulmonary
      outcomes. Heated humidified high-flow nasal cannula oxygen (HHFNC O2) may
      decrease such events. We hypothesized that patients randomized to prophylactic
      HHFNC O2 would develop fewer pulmonary complications compared to conventional O2
      therapy. METHODS AND PATIENTS: Fifty-one patients were randomized to HHFNC O2 vs.
      conventional O2. The primary outcome was a composite of postoperative pulmonary
      complications. Secondary outcomes included oxygenation and length of stay.
      Continuous variables were compared with t-test or Mann-Whitney-U test,
      categorical variables with Fisher's Exact test. RESULTS: There were no
      differences in postoperative pulmonary complications based on intention to treat
      [two in HHFNC O2 (n=25), two in control (n=26), p=0.680], and after exclusion of
      patients who discontinued HHFNC O2 early [one in HHFNC O2 (n=18), two in control
      (n=26), p=0.638]. Discomfort from HHFNC O2 occurred in 11/25 (44%); 7/25 (28%)
      discontinued treatment. CONCLUSIONS: Pulmonary complications were rare after
      thoracic surgery. Although HHFNC O2 did not convey significant benefits, these
      results need to be interpreted with caution, as our study was likely underpowered
      to detect a reduction in pulmonary complications. High rates of patient-reported
      discomfort with HHFNC O2 need to be considered in clinical practice and future
      trials.

PMID- 28454061
TI  - Evaluation of a pilot innovative cognitive-behavioral therapy-based
      psychoeducation group treatment for functional non-epileptic attacks.
AB  - A high proportion of patients presenting at epilepsy clinics experience
      functional non-epileptic attacks (FNEA), and while psychological treatment is
      generally thought to be the required intervention, evidence regarding
      psychological treatment of FNEA is limited. A small number of psychoeducation
      treatments have been evaluated, with promising results. As part of routine care
      within a neuropsychiatry service, a 3-session cognitive-behavior therapy- (CBT-)
      informed psychoeducation group was developed. Patients with comorbid epilepsy
      were included. The group's effectiveness was evaluated in terms of attack
      frequency, mood, illness perception, dissociative experiences, and patient
      feedback. Pre- and post-treatment data were obtained for 19 patients. The
      proportion of patients experiencing attacks significantly decreased, with almost
      40% of treatment completers reporting being attack-free at the end of treatment.
      Significant improvements were also found on level of psychological distress,
      illness beliefs, and understanding of the condition. No significant changes in
      mood or general functioning were observed. High satisfaction was reported by
      almost all patients. Treatment outcome was not significantly affected by the
      level of dissociative experiences. The results suggest that CBT-based
      psychoeducation group treatment can be a beneficial part of treatment for those
      with FNEA, even for those experiencing high levels of dissociation. Further
      controlled studies with larger sample sizes are required.

PMID- 28454062
TI  - Self-assembled dehydropeptide nano carriers for delivery of ornidazole and
      curcumin.
AB  - In the recent studies, it has been demonstrated that incorporation of unnatural
      amino acid, alpha,beta-dehydrophenylalanine, in small peptides results in stable
      self-assembled nanostructures with different sizes and shapes. Here, we have
      replaced the natural amino acid, phenylalanine, from our earlier reported work on
      self-assembled peptide, Boc-Pro-Phe-Gly-OMe, with a constrained dehydro amino
      acid, alpha,beta-dehydrophenylalanine, to study its influence on self-assembled
      nanostructures. Dehydrotripeptide, Boc-Pro-DeltaPhe-Gly-OMe, self-assembled into
      nanostructures in aqueous solutions and formed hydrophobic matrix with improved
      encapsulation efficiency of hydrophobic molecules. The hydrodynamic size of
      peptide nanostructures from DLS study was found to be ~257nm. The morphology and
      size of the loaded nanoparticles were also determined by TEM. To improve aqueous
      dispersibility the projected nanostructures for efficient use in drug delivery,
      self-assembled dehydropeptide nano carriers were further stabilized with Vitamin
      E-TPGS. The final complex drug nanoparticles provided controlled drug release.
      These findings demonstrated that incorporation of constrained dehydro amino acids
      in peptides have the potential to construct stable nanostructures for development
      of nano materials with controlled drug release.

PMID- 28454063
TI  - Interaction of amino acid-functionalized silver nanoparticles and Candida
      albicans polymorphs: A deep-UV fluorescence imaging study.
AB  - The interaction of the tryptophan functionalized Ag nanoparticles and live
      Candida albicans cells was studied by synchrotron excitation deep-ultraviolet
      (DUV) fluorescence imaging at the DISCO beamline of Synchrotron SOLEIL. DUV
      imaging showed that incubation of the fungus with functionalized nanoparticles
      results in significant increase in the fluorescence signal. The analysis of the
      images revealed that the interaction of the nanoparticles with (pseudo)hyphae
      polymorphs of the diploid fungus was less pronounced than in the case of yeast
      cells or budding spores. The changes in the intensity of the fluorescence signals
      of the cells after incubation were followed in [327-353nm] and [370-410nm]
      spectral ranges that correspond to the fluorescence of tryptophan in non-polar
      and polar environment, respectively. As a consequence of the environmental
      sensitivity of the silver-tryptophan fluorescent nanoprobe, we were able to
      determine the possible accumulation sites of the nanoparticles. The analysis of
      the intensity decay kinetics showed that the photobleaching effects were more
      pronounced in the case of the functionalized nanoparticle treated cells. The
      results of time-integrated emission in the mentioned spectral ranges suggested
      that the nanoparticles penetrate the cells, but that the majority of the
      nanoparticles attach to the cells' surfaces.

PMID- 28454064
TI  - Withaferin-A, a steroidal lactone encapsulated mannose decorated liposomes
      ameliorates rheumatoid arthritis by intriguing the macrophage repolarization in
      adjuvant-induced arthritic rats.
AB  - In order to develop a better therapeutic approach for the treatment of rheumatoid
      arthritis (RA), withaferin-A; a steroidal lactone incorporated with mannosylated
      liposomes (ML-WA) was administered to adjuvant induced arthritic rats in intent
      to target the synovial macrophages. The confocal microscopy studies showed a
      successful internalization of ML-WA in the primarily isolated synovial
      macrophages. Consequently, targeting synovial macrophages via ML-WA reduced the
      oxidative stress (ROS and NO), and paw edema, however, a progressive gain in the
      body weight was observed in AIA rats. ML-WA treatment upregulated the production
      of osteoprotegerin (OPG) and downregulated the release of receptor activator of
      nuclear factor-kappaB ligand (RANKL), favoring osteoclastogenesis negatively.
      Correspondingly, the ankle joints were found intact with no bone erosion and
      cartilage degradation in ML-WA treated AIA rats as evidenced by histopathological
      analysis. Also, synovial macrophage assessment showed that the concentration and
      the gene amplification of M1 macrophage mediated pro-inflammatory mediators (TNF
      alpha, IL-1beta, IL-6, MCP-1 and VEGF) were curtailed in ML-WA treated AIA rats.
      In contrast, anti-inflammatory cytokine (IL-10) was found abundantly released.
      Furthermore, the mRNA expression of the M1 surface marker (CD86) was found down
      regulated, whereas, M2 marker (CD163) was highly amplified in ML-WA treated
      synovial macrophages of arthritic rats. Cumulatively, our result signified that
      targeted delivery of ML-WA ameliorated the severity of inflammation and bone
      resorption in AIA rats via M1 to M2 macrophage repolarization.

PMID- 28454065
TI  - Quantitative measurements of intercellular adhesion between a macrophage and
      cancer cells using a cup-attached AFM chip.
AB  - Intercellular adhesion between a macrophage and cancer cells was quantitatively
      measured using atomic force microscopy (AFM). Cup-shaped metal hemispheres were
      fabricated using polystyrene particles as a template, and a cup was attached to
      the apex of the AFM cantilever. The cup-attached AFM chip (cup-chip) approached a
      murine macrophage cell (J774.2), the cell was captured on the inner concave of
      the cup, and picked up by withdrawing the cup-chip from the substrate. The cell
      attached chip was advanced towards a murine breast cancer cell (FP10SC2), and
      intercellular adhesion between the two cells was quantitatively measured. To
      compare cell adhesion strength, the work required to separate two adhered cells
      (separation work) was used as a parameter. Separation work was almost 2-fold
      larger between a J774.2 cell and FP10SC2 cell than between J774.2 cell and three
      additional different cancer cells (4T1E, MAT-LyLu, and U-2OS), two FP10SC2 cells,
      or two J774.2 cells. FP10SC2 was established from 4T1E as a highly metastatic
      cell line, indicates separation work increased as the malignancy of cancer cells
      became higher. One possible explanation of the strong adhesion of macrophages to
      cancer cells observed in this study is that the measurement condition mimicked
      the microenvironment of tumor-associated macrophages (TAMs) in vivo, and J774.2
      cells strongly expressed CD204, which is a marker of TAMs. The results of the
      present study, which were obtained by measuring cell adhesion strength
      quantitatively, indicate that the fabricated cup-chip is a useful tool for
      measuring intercellular adhesion easily and quantitatively.

PMID- 28454066
TI  - Direct measurement of IgM-Antigen interaction energy on individual red blood
      cells.
AB  - Most blood grouping tests rely on the principle of red blood cells (RBCs)
      agglutination. Agglutination is triggered by the binding of specific blood
      grouping antibodies to the corresponding RBC surface antigen on multiple cells.
      The interaction energies between blood grouping antibodies and antigens have been
      poorly defined in immunohaematology. Here for the first time, we functionalized
      atomic force microscope (AFM) cantilevers with the IgM form of blood grouping
      antibodies to probe populations of individual RBCs of different groups under
      physiological conditions. The force-mapping mode of AFM allowed us to measure
      specific antibody - antigen interactions, and simultaneously localize and
      quantify antigen sites on the scanned cell surface. This study provides a new
      insight of the interactions between IgM antibodies and its corresponding antigen.
      The technique and information can be translated to develop better blood typing
      diagnostics and optimize target-specific drug delivery for medical applications.

PMID- 28454067
TI  - Assessment of the SWAT model to simulate a watershed with limited available data
      in the Pampas region, Argentina.
AB  - Argentina has been among the world leaders in the production and export of
      agricultural products since the 1990s. The Carcarana River Lower Basin (CRLB), a
      cropland of the Pampas region supplied by extensive rainfall, is located in an
      area with few streamgauging and other hydrologic/water-quality stations.
      Therefore, limited hydrologic data are available resulting in limited water
      resources assessment. This work explores the application of Soil and Water
      Assessment Tool (SWAT) model to the CRLB in the Santa Fe province of the Pampas
      region. The analysis of field and remote-sensing data characterizing hydrology,
      water quality, soil types, land use/land cover, management practices, and crop
      yield, guarantee a comprehensive SWAT modeling approach. A combined manual and
      automated calibration and validation process incorporating sensitivity and
      uncertainty analysis is performed using information concerning interior watershed
      processes. Eleven N/P fertilizer rates are selected to simulate the impact of N
      fertilizer on crop yield, plant uptake, as well as runoff and leaching losses.
      Different indices (partial factor productivity, agronomic efficiency, apparent
      crop recovery efficiency of applied nutrient, internal utilization efficiency,
      and physiological efficiency) are considered to assess nitrogen-use efficiency.
      The overall quality of the fit is satisfactory considering the input data
      limitations. This work provides, for the first time in Argentina, a reliable tool
      to simulate yield response to soil quality and water availability capable to meet
      defined environmental targets to support decision making on planning public
      policies and private activities on the Pampas region.

PMID- 28454068
TI  - Biochar-based water treatment systems as a potential low-cost and sustainable
      technology for clean water provision.
AB  - Approximately 600 million people lack access to safe drinking water, hence
      achieving Sustainable Development Goal 6 (Ensure availability and sustainable
      management of water and sanitation for all by 2030) calls for rapid translation
      of recent research into practical and frugal solutions within the remaining 13
      years. Biochars, with excellent capacity to remove several contaminants from
      aqueous solutions, constitute an untapped technology for drinking water
      treatment. Biochar water treatment has several potential merits compared to
      existing low-cost methods (i.e., sand filtration, boiling, solar disinfection,
      chlorination): (1) biochar is a low-cost and renewable adsorbent made using
      readily available biomaterials and skills, making it appropriate for low-income
      communities; (2) existing methods predominantly remove pathogens, but biochars
      remove chemical, biological and physical contaminants; (3) biochars maintain
      organoleptic properties of water, while existing methods generate carcinogenic by
      products (e.g., chlorination) and/or increase concentrations of chemical
      contaminants (e.g., boiling). Biochars have co-benefits including provision of
      clean energy for household heating and cooking, and soil application of spent
      biochar improves soil quality and crop yields. Integrating biochar into the water
      and sanitation system transforms linear material flows into looped material
      cycles, consistent with terra preta sanitation. Lack of design information on
      biochar water treatment, and environmental and public health risks constrain the
      biochar technology. Seven hypotheses for future research are highlighted under
      three themes: (1) design and optimization of biochar water treatment; (2)
      ecotoxicology and human health risks associated with contaminant transfer along
      the biochar-soil-food-human pathway, and (3) life cycle analyses of carbon and
      energy footprints of biochar water treatment systems.

PMID- 28454070
TI  - Principles and applications of photoelectrochemical sensing strategies based on
      biofunctionalized nanostructures.
AB  - Photoelectrochemical (PEC) biosensing is a popular research hotspot that has
      attracted substantial attention from chemists and biologists due to its low cost
      and desirable sensitivity. The PEC biosensing mainly refers to the influence of
      the interaction between recognition element and analyte on photocurrent signal,
      which involves the charge and energy transfer of PEC reaction between electron
      donor/acceptor and photoactive material upon light irradiation. Understanding the
      fundamentals of PEC strategy benefits the development of next-generation PEC
      sensors. However, the research on detection mechanism of PEC sensors is in the
      initial stage and need to be further exploited. Thus, with a particular focus on
      the signal transduction formats, this review highlights the novel concept on PEC
      sensing strategies, and categorizes the recent illustrative examples into three
      signaling principles: reactant determinant, electron transfer and energy
      transfer, providing the comprehensive design guidelines for researchers to
      develop more advanced PEC sensors. The prospects and challenges for future work
      are also included.

PMID- 28454069
TI  - CNS bioavailability and radiation protection of normal hippocampal neurogenesis
      by a lipophilic Mn porphyrin-based superoxide dismutase mimic, MnTnBuOE-2-PyP5.
AB  - Although radiation therapy can be effective against cancer, potential damage to
      normal tissues limits the amount that can be safely administered. In central
      nervous system (CNS), radiation damage to normal tissues is presented, in part,
      as suppressed hippocampal neurogenesis and impaired cognitive functions. Mn
      porphyrin (MnP)-based redox active drugs have demonstrated differential effects
      on cancer and normal tissues in experimental animals that lead to protection of
      normal tissues and radio- and chemo-sensitization of cancers. To test the
      efficacy of MnPs in CNS radioprotection, we first examined the tissue levels of
      three different MnPs - MnTE-2-PyP5+(MnE), MnTnHex-2-PyP5+(MnHex), and MnTnBuOE-2
      PyP5+(MnBuOE). Nanomolar concentrations of MnHex and MnBuOE were detected in
      various brain regions after daily subcutaneous administration, and MnBuOE was
      well tolerated at a daily dose of 3mg/kg. Administration of MnBuOE for one week
      before cranial irradiation and continued for one week afterwards supported
      production and long-term survival of newborn neurons in the hippocampal dentate
      gyrus. MnP-driven S-glutathionylation in cortex and hippocampus showed
      differential responses to MnP administration and radiation in these two brain
      regions. A better understanding of how preserved hippocampal neurogenesis
      correlates with cognitive functions following cranial irradiation will be helpful
      in designing better MnP-based radioprotection strategies.

PMID- 28454071
TI  - Increased gait variability may not imply impaired stride-to-stride control of
      walking in healthy older adults: Winner: 2013 Gait and Clinical Movement Analysis
      Society Best Paper Award.
AB  - Older adults exhibit increased gait variability that is associated with fall
      history and predicts future falls. It is not known to what extent this increased
      variability results from increased physiological noise versus a decreased ability
      to regulate walking movements. To "walk", a person must move a finite distance in
      finite time, making stride length (Ln) and time (Tn) the fundamental stride
      variables to define forward walking. Multiple age-related physiological changes
      increase neuromotor noise, increasing gait variability. If older adults also
      alter how they regulate their stride variables, this could further exacerbate
      that variability. We previously developed a Goal Equivalent Manifold (GEM)
      computational framework specifically to separate these causes of variability.
      Here, we apply this framework to identify how both young and high-functioning
      healthy older adults regulate stepping from each stride to the next. Healthy
      older adults exhibited increased gait variability, independent of walking speed.
      However, despite this, these healthy older adults also concurrently exhibited no
      differences (all p>0.50) from young adults either in how their stride variability
      was distributed relative to the GEM or in how they regulated, from stride to
      stride, either their basic stepping variables or deviations relative to the GEM.
      Using a validated computational model, we found these experimental findings were
      consistent with increased gait variability arising solely from increased
      neuromotor noise, and not from changes in stride-to-stride control. Thus, age
      related increased gait variability likely precedes impaired stepping control.
      This suggests these changes may in turn precede increased fall risk.

PMID- 28454072
TI  - Fluorescent coumarin-based probe for cysteine and homocysteine with live cell
      application.
AB  - Cysteine (Cys) and homocysteine (Hcy) are two of important biological thiols and
      function as important roles in several biological processes. The development of
      Cys and Hcy probes will help to explore the functions of biothiols in biological
      systems. In this work, a new coumarin-based probe AC, containing an acryloyl
      moiety, was developed for Cys and Hcy detection in cells. Cys and Hcy undergo a
      nucleophilic addition and subsequent cyclization reaction to remove to the
      acryloyl group and yield a fluorescent product, 7-hydroxylcomuarin. The probe AC
      showed good selectivity for cysteine and homocysteine over glutathione and other
      amino acids and had low detection limits of 65nM for Cys and 79nM for Hcy,
      respectively. Additionally, confocal imaging experiments demonstrated that the
      probe AC can be applied to visualize Cys and Hcy in living cells.

PMID- 28454073
TI  - Low-temperature Raman spectra of the 2-(alpha-methylbenzylamino)-5-nitropyridine
      crystal.
AB  - The polar organic 2-(alpha-methylbenzylamino)-5-nitropyridine crystal (MBANP) has
      been studied by Raman spectroscopy at low temperatures (from 300 to 10K). The
      effect of temperature change on the vibrational spectrum is discussed with the
      aid of DFT calculations. The behavior of the Raman spectra indicates that MBANP
      molecules present a different conformation at low temperatures associated with
      the rotation of the phenyl and pyridine rings. Temperature-dependent X-ray
      measurements and differential scanning calorimetry (DSC) analysis were utilized
      as complementary techniques to investigate the structural stability of MBANP
      crystal.

PMID- 28454074
TI  - Photocatalytic degradation of dye using CeO2/SCB composite catalysts.
AB  - The main task of the present work is to enhance the photocatalytic degradation
      efficiency of methylene blue (MB) by using CeO2/sugarcane bagasse (SCB) composite
      catalysts. Homogeneous precipitation method was used to synthesis CeO2-SCB
      composite catalysts by adding SCB powder to precursor solution of Ce base-metal.
      The structural analytical data indicated the pure cubic fluorite structure of
      CeO2. Morphological images revealed the coating of CeO2 layer on high surface
      area of SCB core-shell. The chemical analysis presented spectrum of the Ce 3d in
      CeO2/SCB sample existed in the form of the Ce3+ and Ce4+ mixed- valence states.
      Optical spectra showed the shift of absorption edge towards longer visible region
      upon supporting CeO2 with SCB. The main chemical composition of the SCB was K,
      Ca, and Si. Furthermore, recombination of the photogenerated electrons and holes
      was identified by photoluminescence techniques (PL), the data suggested
      inhibition of electron-hole pairs recombination by the cations from SCB loaded in
      CeO2/SCB composite. Photocatalytic activity of CeO2/SCB catalyst was investigated
      via the degradation of MB under UV-A irradiation. Experimental kinetic data
      followed the pseudo-first order model. CeO2 supported with SCB adsorbent had
      higher photocatalytic activity in dye wastewater treatment compared to the pure
      CeO2. The proposed mechanism explaining the high photocatalytic efficiency of
      CeO2/SCB was associated with high surface properties and the suppression of
      recombination of the photogenerated electron-hole pairs by the SCB adsorbent.

PMID- 28454075
TI  - A novel, highly sensitive, selective, reversible and turn-on chemi-sensor based
      on Schiff base for rapid detection of Cu(II).
AB  - In this work, a novel optical fluoro-chemisensor was designed and synthesized for
      copper (II) ions detection. The sensor film is created by embedded N,N-Bis(2
      hydroxo-5-bromobenzyl)ethylenediamine in poly vinyl chloride (PVC) film in
      presence of dioctyl phthalate (DOP) as plasticizer. The receptor Schiff base
      reveals "off-on" mode with high selectivity, significant sensitivity to Cu(II)
      ions. The selectivity of optical sensor for Cu(II) ions is the result of
      chelation enhanced fluorescence (CHEF). The optimal conditions of pH and response
      time at which higher efficiency of sensor film is performed was found to be 6.8
      and 2.48min. The possible interference of other metal ions in solution was
      examined in presence of different types of metal ions. This film shows high
      selectivity and ultra-sensitivity with low detection limit LOD (1.1*10-8M). Thus,
      these considerable properties make it viable to monitor copper metal ions within
      very low concentration range (0-15*10-6M Cu(II)) and highly selective even in the
      presence of different types of metal ions. The sensor reversibility was achieved
      by utilizing EDTA solution with concentration of 0.1M solution.

PMID- 28454076
TI  - Carbazole based nanoprobe for selective recognition of Fe3+ ion in aqueous
      medium: Spectroscopic insight.
AB  - A simple carbazole based nanoprobe prepared by reprecipitation method shows
      selective sensing behavior for Fe3+ ion in aqueous medium. The prepared SDS
      capped 9-phenyl carbazole nanoparticles (9-PCzNPs) has narrower particle size
      distribution with an average diameter 35nm and zeta potential of -34.3mV
      predicted a good stability with negative surface charge over the nanoparticles.
      The Field Emission Scanning Electron Microscopy (FE-SEM) image showed cubic shape
      morphology of nanoparticles. The aqueous suspension of SDS capped 9-phenyl
      carbazole nanoparticles exhibited aggregation induced enhanced red shifted
      intense emission in comparison with the emission arising from dilute solution of
      9-phenyl carbazole in DCM. The cation recognition test based on fluorescence
      change shows Fe3+ ion induce significant fluorescence quenching, however
      remaining cations responds negligibly. The obtained quenching data fit into Stern
      Volmer relation in the concentration range of 0.0-1.0MUg.mL-1 of Fe3+ ion
      solution and the detection limit is 0.0811MUg.mL-1. The probable mechanism of
      fluorescence quenching of SDS capped 9-PCzNPs is because of adsorption of Fe3+
      ion over the negatively charged surface of NPs through electrostatic interaction.
      Thus the proposed method was successfully applied for the detection of Fe3+ ion
      in environmental water sample.

PMID- 28454077
TI  - Comparison of FTIR-ATR and Raman spectroscopy in determination of VLDL
      triglycerides in blood serum with PLS regression.
AB  - Hypertriglyceridemia, related with triglyceride (TG) in plasma above 1.7mmol/L is
      one of the cardiovascular risk factors. Very low density lipoproteins (VLDL) are
      the main TG carriers. Despite being time consuming, demanding well-qualified
      staff and expensive instrumentation, ultracentrifugation technique still remains
      the gold standard for the VLDL isolation. Therefore faster and simpler method of
      VLDL-TG determination is needed. Vibrational spectroscopy, including FT-IR and
      Raman, is widely used technique in lipid and protein research. The aim of this
      study was assessment of Raman and FT-IR spectroscopy in determination of VLDL-TG
      directly in serum with the isolation step omitted. TG concentration in serum and
      in ultracentrifugated VLDL fractions from 32 patients were measured with
      reference colorimetric method. FT-IR and Raman spectra of VLDL and serum samples
      were acquired. Partial least square (PLS) regression was used for calibration and
      leave-one-out cross validation. Our results confirmed possibility of reagent-free
      determination of VLDL-TG directly in serum with both Raman and FT-IR
      spectroscopy. Quantitative VLDL testing by FT-IR and/or Raman spectroscopy
      applied directly to maternal serum seems to be promising screening test to
      identify women with increased risk of adverse pregnancy outcomes and patient
      friendly method of choice based on ease of performance, accuracy and efficiency.

PMID- 28454078
TI  - New complexes of Cu(II) with dipicolinate and pyridyl-based ligands: An
      experimental and DFT approach.
AB  - The three novel mononuclear copper(II) complexes with dipicolinate and pyridyl
      based ligands [Cu(dipic)(L)(OH2)] (L=4-picoline, vinylpyridine, 4-styrylpyridine;
      dipic2-=dipicolinate) were afforded and structurally characterized. X-ray
      diffraction studies accounted for slight distorted square-pyramidal structures in
      which the dianion dipic2- acts as a tridentate ligand in a mer-fashion, the N
      donor species occupy an in-plane position, and a water molecule was detected
      apically coordinated. To assess the effect of the nature of the pyridyl
      substituent (para position) on electronic properties, other complexes were also
      synthesized: [Cu(dipic)(py)(OH2)], [{Cu(dipic)(OH2)}2(MU-pyz)] and
      [{Cu(dipic)(OH2)}(MU-pypy){Cu(dipic)}] (py=pyridine, pyz=pyrazine, pypy=(E)-1,2
      bis(pyridine-4-yl)ethane). Absorptive behavior in the UV-VIS region was studied
      in solution and in the solid state (reflectance measurements). Additionally,
      geometry and population analyses were conducted by means of DFT calculations.
      Electronic UV-VIS spectra were simulated for both dinuclear complexes in the
      framework of the TD-DFT methodology to assign the origin of the absorption bands.

PMID- 28454079
TI  - Burnout and its association with extracurricular activities among medical
      students in Saudi Arabia.
AB  - Objectives: To assess levels of burnout in medical students, and to explore the
      influence of extracurricular activities on burnout at a medical school in Saudi
      Arabia. Methods: This cross-sectional study was conducted with first to fourth
      year medical students at King Saud bin Abdulaziz University for Health Sciences
      (KSAU-HS) in Riyadh, Saudi Arabia. Socio-demographic, burnout level (the Maslach
      Burnout Inventory-Student Survey, MBI-SS) and participation in extracurricular
      activities data were collected using a self-administered questionnaire.
      Statistical analyses were performed using the Pearson's chi-square test and
      binary logistic regression. Results: From the 306 medical students approached,
      249 (81.4%) completed the questionnaire. The level of high burnout was 67.1%
      (n=167). The study revealed that the majority (62.3%, n=155) of students had high
      levels of cynicism, 58.6% (n=146) had high levels of emotional exhaustion, and
      60.2% (n=150) had low levels of professional efficacy. Most of the students
      (73.5%, n=183) participated in extracurricular activities, and 112 (45%) students
      were organizers of extracurricular activities. No significant association was
      found between burnout levels and the frequency of involvement in extracurricular
      activities (chi2=2.2, df=2, p=0.333). However, students who were organizing
      extracurricular activities were less likely to have low professional efficacy
      (OR=0.51, 95% CI: 0.27- 0.96). Conclusions: High levels of burnout were reported
      at this medical school. Although the burnout level is not significantly
      associated with the frequency of involvement in extracurricular activities,
      leading and organizing extracurricular activities might result in lower levels of
      burnout. Therefore, improving the students' leadership skills should be
      considered in curriculum planning, and greater emphasis should be placed on the
      quality of involvement in extracurricular activities rather than the quantity.

PMID- 28454081
TI  - Expression characteristic of CXCR1 in different breast tissues and the relevance
      between its expression and efficacy of neo-adjuvant chemotherapy in breast
      cancer.
AB  - OBJECTIVE: To investigate chemokine receptor CXCR1 expression characteristic in
      different breast tissues and analyze the relationship between CXCR1 expression
      changes in breast cancer tissue and efficacy of neo-adjuvant chemotherapy.
      RESULTS: Chemokine receptor CXCR1 was lowly expressed in normal breast tissues
      and breast fibroadenoma, but highly expressed in breast cancer. It was
      significantly correlated with pathological stage, tumor cell differentiation, and
      lymph node metastasis (P < 0.05). After neo-adjuvant chemotherapy, CXCR1
      expression in breast cancer tissues decreased. Among these 104 breast cancer
      patients with different molecular subtypes, the survival rate with Luminal A was
      the highest, followed by the Luminal B breast cancer, TNBC was the worst.
      MATERIALS AND METHODS: 104 cases with breast carcinoma, 20 cases with normal
      breast and 20 cases with breast fibroadenoma were included and followed up.
      Immunohistochemistry was used to detect the expression of CXCR1 in the various
      tissues. The relationship between the CXCR1 expression changes in breast cancer
      biopsies and surgical specimens, as well as the efficacy of neo-adjuvant
      chemotherapy, was analyzed. CONCLUSIONS: Chemokine receptor CXCR1 could be used
      as an indicator to predict benign or malignant breast disease, and it can even
      predict the malignancy degree of breast cancer, as well as its invasive ability
      and prognosis.

PMID- 28454085
TI  - Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib
      in germline BRCA1/2 mutated patients with advanced ovarian cancer.
AB  - BACKGROUND: The PARP inhibitor olaparib was recently granted Food and Drug
      Administration (FDA) accelerated approval in patients with advanced BRCA1/2
      mutation ovarian cancer. However, antitumor responses are observed in only
      approximately 40% of patients and the impact of baseline clinical factors on
      response to treatment remains unclear. Although platinum sensitivity has been
      suggested as a marker of response to PARP inhibitors, patients with platinum
      resistant disease still respond to olaparib. RESULTS: 108 patients with advanced
      BRCA1/2 mutation ovarian cancers were included. The interval between the end of
      the most recent platinum chemotherapy and PARPi (PTPI) was used to predict
      response to olaparib independent of conventional definition of platinum
      sensitivity. RECIST complete response (CR) and partial response (PR) rates were
      35% in patients with platinum-sensitive versus 13% in platinum-resistant
      (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates
      were 42% in patients with PTPI greater than 52 weeks and 18% in patients with
      PTPI less than 52 weeks (p=0.016). No association was found between baseline
      clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2
      mutations, prior history of breast cancer and prior chemotherapy for breast
      cancer, and the response to olaparib. METHODS: We conducted an international
      multicenter retrospective study to investigate the association between baseline
      clinical characteristics of patients with advanced BRCA1/2 mutation ovarian
      cancers from eight different cancer centers and their antitumor response to
      olaparib. CONCLUSION: PTPI may be used to refine the prediction of response to
      PARP inhibition based on the conventional categorization of platinum sensitivity.

PMID- 28454086
TI  - Association between genetic variants and esophageal cancer risk.
AB  - We investigated whether single nucleotide polymorphisms (SNPs) in the nuclear
      assembly factor 1 (NAF1) and TNFAIP3-interacting protein 1 (TNIP1) gene were
      associated with susceptibility to esophageal cancer in a Chinese Han population.
      Five SNPs were genotyped and their relationship with esophageal cancer risk was
      analyzed in a sample of 386 esophageal cancer patients and 495 unrelated healthy
      controls recruited from the First Affiliated Hospital of Xi'an Jiaotong
      University. Patients with the AG genotype of rs2320615 were at lower risk of
      developing esophageal cancer than those with the GG genotype (adjusted odds ratio
      [OR] = 0.64, 95% confidence interval [CI] = 0.46-0.90, P = 0.009). The rs2320615
      SNP was found to be associated with a decreased the risk of esophageal cancer in
      the dominant model (adjusted OR = 0.70, 95% CI = 0.51-0.96, P = 0.026). These
      results provide the first evidence that the rs2320615 in NAF1 was associated with
      reduced risk of esophageal cancer. Further studies with larger samples are
      warranted to confirm our findings.

PMID- 28454092
TI  - HOXB7 promotes tumor progression via bFGF-induced activation of MAPK/ERK pathway
      and indicated poor prognosis in hepatocellular carcinoma.
AB  - The homeobox-containing gene HOXB7 plays an important role in the pathogenesis
      and progression of many cancers, yet its role in hepatocellular carcinoma (HCC)
      remains unclear. This study comprehensively analyzed the expression and clinical
      significance of HOXB7 in HCC and explored its potential mechanism in tumor
      progression. We found HOXB7 was highly expressed in HCC cell lines with highly
      metastatic potential and cancerous tissues from patients with tumor recurrence.
      The abilities of proliferation, migration, and invasion were notably decreased by
      depletion of HOXB7, and were enhanced by its enforced expression in vitro. HOXB7
      expression was positively correlated with tumor progression and lung metastasis
      in vivo. The gene microarray data implied that HOXB7 affects biological functions
      of HCC cells through MAPK/ERK pathway activation. Further study confirmed that
      the effect of HOXB7 in activating MAPK/ERK pathway via induction of basic
      fibroblast growth factor (bFGF) secretion, and the inhibition of bFGF secretion
      could abolish MAPK/ERK pathway activation after ectopic expression of HOXB7.
      Chromatin immunoprecipitation experiments and luciferase reporter assays
      confirmed that HOXB7 promoted bFGF secretion via binding its promoter directly.
      Furthermore, the clinical significance of HOXB7 expression was confirmed using
      tissue microarrays containing 394 HCC tissue specimens. Patients with high HOXB7
      expression showed shorter survival times and higher recurrence rates, and HOXB7
      was an independent indicator for survival and recurrence. Overall, HOXB7 promotes
      HCC cell proliferation, migration, and invasion through the bFGF-induced MAPK/ERK
      pathway activation. It might be a novel prognostic factor in HCC and a promising
      therapeutic target for tumor metastasis and recurrence.

PMID- 28454097
TI  - Upregulation of calprotectin in mild IgE-mediated ovalbumin hypersensitivity.
AB  - Calprotectin, also known as S100A8/A9, has been linked to gut inflammation caused
      by IgE-mediated food hypersensitivities, but the pathophysiologic abnormalities
      it causes remain to be determined. We created a mild food hypersensitivity model
      through oral gavage of ovalbumin in Norway brown rats without using immune
      adjuvant. Changes in the levels of calprotectin and inflammation-associated
      cytokines were then observed over time. We found that fecal calprotectin as well
      as jejunal and liver TLR4, TNF-alpha, NF-kappaB, IL-1beta, and IL-6 were
      upregulated in hypersensitive rats. Additionally, the influence of calprotectin
      on CD4+ T and dendritic cells was observed by co-culturing CD4+ T cells with
      dendritic cells, which revealed a shift toward increased Th2 T cells in
      calprotectin-treated cultures. These results suggest that calprotectin, along
      with other inflammatory factors, promotes the inflammation seen in mild food
      allergy.

PMID- 28454098
TI  - The impact of receptor recycling on the exocytosis of alphavbeta3 integrin
      targeted gold nanoparticles.
AB  - Among the diverse factors that may influence the therapeutic outcomes, the
      exocytosis of targeted drug delivery systems (TDDS) and its relationship with the
      corresponding receptor receive little attentions. In this study, cRGDfK modified
      gold nanoparticles (cRGDfK-PEG-AuNPs) were synthesized, and their cellular
      transportation including endocytosis and exocytosis, as well as the potential
      relations with alphavbeta3 integrin were carefully studied. The results showed
      that the enhanced and fast internalization of cRGDfK-PEG-AuNPs into U87 cells was
      associated with the high expression level of alphavbeta3 integrin. Importantly,
      the significant exocytosis of cRGDfK-PEG-AuNPs, but not the PEG conjugated gold
      nanoparticles (PEG-AuNPs), was found under the in vivo-simulated serum containing
      conditions. Interestingly, the exocytosis kinetics of nanoparticles was
      demonstrated to be tightly related with the recycling of the alphavbeta3
      integrin, although the exocytosis of cRGDfK-PEG-AuNPs slightly lagged behind the
      receptor recycling. In effect, our findings uncover a new underlying behavior of
      receptor mediated TDDS and have implication for their rational design and
      application in the future.

PMID- 28454099
TI  - Homoharringtonine targets Smad3 and TGF-beta pathway to inhibit the proliferation
      of acute myeloid leukemia cells.
AB  - Homoharringtonine (HHT) has long and widely been used in China for the treatment
      of acute myeloid leukemia (AML), the clinical therapeutic effect is significant
      but the working mechanism is poorly understood. The purpose of this study is to
      screen the possible target for HHT with virtual screening and verify the findings
      by cell experiments. Software including Autodock, Python, and MGL tools were
      used, with HHT being the ligand and proteins from PI3K-Akt pathway, Jak-stat
      pathway, TGF-beta pathway and NK-kappaB pathway as the receptors. Human AML cell
      lines including U937, KG-1, THP-1 were cultured and used as the experiment cell
      lines. MTT assay was used for proliferation detection, flowcytometry was used to
      detect apoptosis and cell cycle arrest upon HHT functioning, western blotting was
      used to detect the protein level changes, viral shRNA transfection was used to
      suppress the expression level of the target protein candidate, and viral mRNA
      transfection was used for over-expression. Virtual screening revealed that smad3
      from TGF-beta pathway might be the candidate for HHT binding. In AML cell line
      U937 and KG-1, HHT can induce the Ser423/425 phosphorylation of smad3, and this
      phosphorylation can subsequently activate the TGF-beta pathway, causing cell
      cycle arrest at G1 phase in U937 cells and apoptosis in KG-1 cells, knockdown of
      smad3 can impair the sensitivity of U937 cell to HHT, and over-expression of
      smad3 can re-establish the sensitivity in both cell lines. We conclude that smad3
      is the probable target protein of HHT and plays an important role in the
      functioning mechanism of HHT.

PMID- 28454100
TI  - A mathematical theory of the transcription repression (TR) therapy of cancer -
      whether and how it may work.
AB  - Transcription repression (TR) therapy of cancer has been widely discussed. Here,
      TR refers to global repression of transcription rather than specific targeting of
      cancer-causing genes such as MYC. TR drugs inhibit transcription by binding to
      the transcribed DNA or to RNA polymerase; for example, actinomycin D has been
      extensively used in research and therapy to shut down transcription globally [1
      7]. As proliferating cells demand a high rate of transcription, restricting
      transcript production could be effective in slowing down cell proliferation.
      However, TR also deprives other less proliferative cells of new transcripts, thus
      leading to substantial toxicity [1, 8, 9]. We now develop a mathematical theory
      to exploit the greater demand for transcription in highly proliferating cells. A
      new strategy, referred to as the TRR (transcript repression-recovery) model,
      would insert a recovery phase to allow the more slowly proliferating cells to
      recover. It is most effective to have strong blocking for a short period (a few
      hours) followed by a longer recovery phase in each cell cycle. Hence, TRR can
      potentially achieve selective killing of cells based on their global
      transcription needs but precise fine-tuning is necessary.

PMID- 28454101
TI  - MiR-146a negatively regulates dectin-1-induced inflammatory responses.
AB  - Dectin-1 is the critical sensor for beta-glucan from Candida which is the most
      common human fungal pathogen and cause superficial and system infection.
      MicroRNAs (miRNAs) play crucial roles in regulating innate immunity. However, the
      functional role of miRNAs in inflammatory response dependent on the activation of
      dectin-1 pathway has not been defined. In the present study, we found insoluble
      beta-glucan from the cell wall of Candida albicans (CaIG) was able to increase
      the production of of IL-6 and TNFalpha through Dectin-1-Syk-NF-kappaB and p38MAPK
      pathway. MiRNAs profiles combined with real-time PCR validation revealed that miR
      146a, miR-30-5p, miR-210-3p expression level were increased in THP-1 cells
      treated with CaIG. The interaction between Dectin-1 and CaIG resulted in an long
      lasting increase of miR-146a expression dependent on Dectin-1-Syk-NF-kappaB,
      p38MAPK, contrasting with a rapid and transient increase of IL-6 and TNFalpha.
      Overexpression of miR-146a significantly suppressed the production of IL-6 and
      TNFalpha. MiR-146a mimics inhibited CaIG-induced activity of p-IkappaBalpha and
      translocation of NF-kappaB p65. Luciferase reporter assays showed miR-146a
      inhibited NF-kappaB promoter-binding activity. Together, our data suggest miR
      146a may play the potent negative feedback regulator in inflammatory response
      following Dectin-1 stimulation.

PMID- 28454102
TI  - An inverse association between tea consumption and colorectal cancer risk.
AB  - It is well known that the tea extracts, mainly polyphenols as chemo-preventive
      elements, could act as cancer progression blockers. Although the association
      between tea consumption and colorectal cancer risk has been widely investigated,
      the results still remain inconsistent. We conducted a dose-response meta-analysis
      to evaluate their relationships by enrolling qualified 29 literatures. The
      summary odds ratio (OR) of colorectal cancer for the highest vs. lowest tea
      consumption was 0.93 with 0.87-1.00 of 95% confidence intervals (CIs) among all
      studies with modest heterogeneity (P = 0.001, I2 = 43.4%). Stratified analysis
      revealed that tea, especially green tea, had a protective effect among female and
      rectal cancer patients. Particularly, the dose-response analysis showed that
      there was a significant inverse association between an increment of 1 cup/day of
      tea consumption and colorectal cancer risk in the subgroup of the green tea
      drinking (OR = 0.98, 95% CI = 0.96-1.01, Pnonlinear = 0.003) and female (OR =
      0.68, 95% CI = 0.56-0.81, Pnonlinear < 0.001). Our findings indicate that tea
      consumption has an inverse impact on colorectal cancer risk, which may have
      significant public health implications in the prevention of colorectal cancer and
      further similar researches.

PMID- 28454103
TI  - Subchronic arsenism-induced oxidative stress and inflammation contribute to
      apoptosis through mitochondrial and death receptor dependent pathways in chicken
      immune organs.
AB  - In many organ dysfunctions, arsenic and its compounds are well known to induce
      apoptosis by the mitochondria and death receptor apoptotic pathways in liver and
      airway. However, it is less reported that which signaling pathways contribute to
      excessive apoptosis of chicken immune organs, a major target of toxic metals
      biotransformation, which suffer from subchronic arsenism. In this study, we
      investigated whether the mitochondria or death receptor apoptotic pathways
      activated in the immune organs (spleen, thymus and bursa of Fabricius) of one-day
      old male Hy-line chickens exposed to arsenic trioxide (As2O3), which were fed on
      diets supplemented with 0, 0.625, 1.25 and 2.5 mg/kg BW of As2O3 for 30, 60 and
      90 days. We found that (1) Oxidative damage and inflammatory response were
      confirmed in the immune organs of chickens fed on As2O3 diet. (2) Subchronic
      arsenism induced typical apoptotic changes in ultrastructure. (3) TdT-mediated
      dUTP Nick-End Labeling (TUNEL) showed that the number of apoptotic cells
      significantly increased under subchronic arsenism. (4) As2O3-induced apoptosis of
      immune organs involved in mitochondrial pathway (decrease of B-cell lymphoma-2
      (Bcl-2) and increase of protein 53 (p53), Bcl-2 Associated X Protein (Bax),
      caspase-9, caspase-3) and death receptor pathway (increase of factor associated
      suicide (Fas) and caspase-8). In conclusion, this work is the first to
      demonstrate that the activation of mitochondria and death receptor apoptosis
      pathways can lead to excessive apoptosis in immune organs of chickens, which
      suffer from subchronic arsenism, meanwhile, oxidative stress as well as
      subsequent inflammatory is a crucial driver of apoptosis.

PMID- 28454104
TI  - RNA sequencing-based cell proliferation analysis across 19 cancers identifies a
      subset of proliferation-informative cancers with a common survival signature.
AB  - Despite advances in cancer diagnosis and treatment strategies, robust prognostic
      signatures remain elusive in most cancers. Cell proliferation has long been
      recognized as a prognostic marker in cancer, but the generation of comprehensive,
      publicly available datasets allows examination of the links between cell
      proliferation and cancer characteristics such as mutation rate, stage, and
      patient outcomes. Here we explore the role of cell proliferation across 19
      cancers (n = 6,581 patients) by using tissue-based RNA sequencing data from The
      Cancer Genome Atlas Project and calculating a 'proliferative index' derived from
      gene expression associated with Proliferating Cell Nuclear Antigen (PCNA) levels.
      This proliferative index is significantly associated with patient survival (Cox,
      p-value < 0.05) in 7 of 19 cancers, which we have defined as "proliferation
      informative cancers" (PICs). In PICs, the proliferative index is strongly
      correlated with tumor stage and nodal invasion. PICs demonstrate reduced baseline
      expression of proliferation machinery relative to non-PICs. Additionally, we find
      the proliferative index is significantly associated with gross somatic mutation
      burden (Spearman, p = 1.76 x 10-23) as well as with mutations in individual
      driver genes. This analysis provides a comprehensive characterization of tumor
      proliferation indices and their association with disease progression and
      prognosis in multiple cancer types and highlights specific cancers that may be
      particularly susceptible to improved targeting of this classic cancer hallmark.

PMID- 28454105
TI  - Tea consumption and the risk of biliary tract cancer: a systematic review and
      dose-response meta-analysis of observational studies.
AB  - Recent studies have shown that tea consumption is associated with the reduced
      incidence of some types of cancer, possibly including biliary tract cancer.
      However, the epidemiological evidences for the association with risk of biliary
      tract cancer are contradictory. Thus, we performed meta-analysis of published
      observational studies to assess the association between tea consumption and risk
      of biliary tract cancer. Relevant studies were identified by searching PubMed,
      EMBASE, and ISI Web of Science published before October 2016. The Newcastle
      Ottawa Scale was used to evaluate the quality of included studies, and
      publication bias was evaluated using funnel plots, and Begg's and Egger's tests.
      This meta-analysis includes eight studies comprising 18 independent reports. The
      incidence of biliary tract cancer reduced about 34% (significantly) for tea
      intake group in comparison with never intake group (summary odds ratio [OR] =
      0.66; 95% confidence interval [CI] = 0.48-0.85). Additionally, an inverse
      relationship between tea intake and risk of biliary tract cancer was
      statistically significant in women (OR = 0.65; 95 % CI = 0.47-0.83), but not in
      men (OR = 0.86; 95% CI = 0.58-1.13). Dose- response analysis indicated that the
      risk of biliary tract cancer decreased by 4% with each additional cup of tea one
      day (relative risk [RR] = 0.96, 95% CI = 0.93-0.98, p = 0.001). In summary, tea
      intake is associated with decreased risk of biliary tract cancer, especially for
      women.

PMID- 28454108
TI  - Telomere erosion in NF1 tumorigenesis.
AB  - Neurofibromatosis type 1 (NF1; MIM# 162200) is a familial cancer syndrome that
      affects 1 in 3,500 individuals worldwide and is inherited in an autosomal
      dominant fashion. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) represent a
      significant cause of morbidity and mortality in NF1 and currently there is no
      treatment or definite prognostic biomarkers for these tumors. Telomere shortening
      has been documented in numerous tumor types. Short dysfunctional telomeres are
      capable of fusion and it is considered that the ensuing genomic instability may
      facilitate clonal evolution and the progression to malignancy. To evaluate the
      potential role of telomere dysfunction in NF1-associated tumors, we undertook a
      comparative analysis of telomere length in samples derived from 10 cutaneous and
      10 diffused plexiform neurofibromas, and 19 MPNSTs. Telomere length was
      determined using high-resolution Single Telomere Length Analysis (STELA). The
      mean Xp/Yp telomere length detected in MPNSTs, at 3.282 kb, was significantly
      shorter than that observed in both plexiform neurofibromas (5.793 kb; [p =
      0.0006]) and cutaneous neurofibromas (6.141 kb; [p = 0.0007]). The telomere
      length distributions of MPNSTs were within the length-ranges in which telomere
      fusion is detected and that confer a poor prognosis in other tumor types. These
      data indicate that telomere length may play a role in driving genomic instability
      and clonal progression in NF1-associated MPNSTs.

PMID- 28454110
TI  - Personalizing Chinese medicine by integrating molecular features of diseases and
      herb ingredient information: application to acute myeloid leukemia.
AB  - Traditional Chinese Medicine (TCM) has been widely used as a complementary
      medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a
      new classification of Chinese Medicines (CMs) by integrating the latest
      discoveries in disease molecular mechanisms and traditional medicine theory. We
      screened out a set of chemical compounds on basis of AML differential expression
      genes and chemical-protein interactions and then mapped them to Traditional
      Chinese Medicine Integrated Database. 415 CMs contain those compounds and they
      were categorized into 8 groups according to the Traditional Chinese Pharmacology.
      Pathway analysis and synthetic lethality gene pairs were applied to analyze the
      dissimilarity, generality and intergroup relations of different groups. We
      defined hub CM pairs and alternative CM groups based on the analysis result and
      finally proposed a formula to form an effective anti-AML prescription which
      combined the hub CM pairs with alternative CMs according to patients' molecular
      features. Our method of formulating CMs based on patients' stratification
      provides novel insights into the new usage of conventional CMs and will promote
      TCM modernization.

PMID- 28454112
TI  - The challenge of treating hepatitis C virus-associated cryoglobulinemic
      vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral
      agents.
AB  - Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys,
      joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative,
      and neoplastic disorders have been associated with this disorder, hepatitis C
      virus (HCV) is known to be the etiologic agent in the majority of patients.
      Therefore, clinical research has focused on anti-viral drugs and, more recently,
      on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs
      assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their
      efficacy in patients with HCV-associated cryoglobulinemic vasculitis are
      disappointing, possibly due to the inability of the drugs to suppress the immune
      mediated process once it has been triggered.Despite the potential risk of
      exacerbation of the infection, immunosuppression has traditionally been regarded
      as the first-line intervention in cryoglobulinemic vasculitis, especially if
      renal involvement is severe. Biologic agents have raised hopes for more
      manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal
      antibody, is the most widely used biologic drug. It has proved to be safer than
      conventional immunosuppressants, thus substantially changing the natural history
      of HCV-associated cryoglobulinemic vasculitis by providing long-term remission,
      especially with intensive regimens.The present review focuses on the new
      therapeutic opportunities offered by the combination of biological drugs, mainly
      Rituximab, with DAAs.

PMID- 28454113
TI  - Systematic review and meta-analysis of the efficacy and safety of novel
      monoclonal antibodies for treatment of relapsed/refractory multiple myeloma.
AB  - Although two newly launched monoclonal antibodies (mAbs), elotuzumab and
      daratumumab, performed well in patients with relapsed or relapsed/refractory
      multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore
      performed a systematic review and meta-analysis of the most recent clinical
      trials that evaluated elotuzumab and/or daratumumab for the treatment of patients
      with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients
      participating. The overall response rate (ORR) was 57% (95% confidence interval
      [CI]: 38-76%), and the at least very good partial response rate (VGPR) was 32%
      (95% CI: 19-46%). mAb-based regimens prolonged progression-free survival (PFS,
      hazard ratio: 0.52, 95% CI: 0.36-0.75) compared to non-mAb-based regimens.
      Additionally, the efficacy of triplet regimens was superior to that of single or
      doublet regimens. The same trend was observed in a subgroup analysis of
      daratumumab and elotuzumab. The most common grade 3/4 adverse events included
      neutropenia, lymphopenia, thrombocytopenia, anemia, leukopenia, pneumonia, and
      fatigue. Elotuzumab and daratumumab improved the ORR, at least VGPR, and PFS
      compared to non-mAb-based regimens. In a pooled analysis, both mAbs had promising
      efficacy and safety profiles, particularly in triplet regimens. The same trend
      was observed in daratumumab- and elotuzumab-based regimens. Daratumumab triplet
      therapy (daratumumab, lenalidomide, and dexamethasone) was superior to other
      triplet regimens for the treatment of RRMM, and daratumumab monotherapy was more
      effective than either single agent in heavily pretreated MM patients, suggesting
      CD38 is an effective target for treatment of RRMM. Additional clinical studies of
      elotuzumab and daratumumab will be required to validate these results.

PMID- 28454114
TI  - Estimating the effects of transcription factors binding and histone modifications
      on gene expression levels in human cells.
AB  - Transcription factors and histone modifications are vital for the regulation of
      gene expression. Hence, to estimate the effects of transcription factors binding
      and histone modifications on gene expression, we construct a statistical model
      for the genome-wide 15 transcription factors binding data, 10 histone
      modifications profiles and DNase-I hypersensitivity data in three mammalian.
      Remarkably, our results show POLR2A and H3K36me3 can highly and consistently
      predict gene expression in three cell lines. And H3K4me3, H3K27me3 and H3K9ac are
      more reliable predictors than other histone modifications in human embryonic stem
      cells. Moreover, genome-wide statistical redundancies exist within and between
      transcription factors and histone modifications, and these phenomena may be
      caused by the regulation mechanism. In further study, we find that even though
      transcription factors and histone modifications offer similar effects on
      expression levels of genome-wide genes, the effects of transcription factors and
      histone modifications on predictive abilities are different for genes in
      independent biological processes.

PMID- 28454116
TI  - Neuroprotection by IFN-gamma via astrocyte-secreted IL-6 in acute
      neuroinflammation.
AB  - Inflammation eliminates pathogenic infections while also threatening the
      integrity of the central nervous system. In this study, using in vivo and in
      vitro models of acute neuroinflammation, we investigated the mechanisms by which
      inflammation and astrocytes affect neuronal apoptosis. The in vitro model
      mimicked acute neuroinflammation by incubation in IFN-gamma-containing media with
      primary cultured cerebellar granule neurons, with or without cultured astrocytes.
      This quickly induced neuronal apoptosis characterized by cleaved caspase-3
      expression, Hoechst 33342 staining, and intercellular Ca2+ influx, whereas the
      presence of astrocytes significantly protected neurons from these effects. IFN
      gamma in the inflammation media also promoted astrocyte secretion of IL-6,
      essential for protection. The supernatants of rat peripheral blood mononuclear
      cells stimulated by lymphocyte mitogen lipopolysaccharide or concanavalin A were
      used as inflammation media to verify the results. The in vivo model involved a
      peripheral challenge with lipopolysaccharide, with or without recombinant IFN
      gamma, in C57BL/6 mice. This confirmed the in vitro results: anti-IFN-gamma
      antibodies exacerbated the acute course of neuroinflammation and led to neurocyte
      apoptosis in vivo. The pro-inflammatory cytokine IFN-gamma provided
      neuroprotection during acute neuroinflammation via induction of astrocyte
      secreted IL-6. The findings provide novel insights into the mechanisms of
      neuroprotection by IFN-gamma during acute neuroinflammation, and may impact
      therapies for inflammation-related central nervous system injury and disease.

PMID- 28454117
TI  - Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS
      cells.
AB  - Epstein-Barr virus (EBV) latently infects malignant epithelial cells in
      approximately 10% of all gastric cancers. Latent membrane protein 1 (LMP1), an
      oncogenic protein, plays an important role in malignant transformation in EBV
      associated nasopharyngeal carcinoma and B-cell lymphoma; however, its expression
      has not been detected in EBV-associated gastric cancer. To address why LMP1 has
      not been detected in EBV-positive gastric tumors, we focused on the interactions
      between LMP1-positive and -negative cells and stably expressed LMP1 in the
      gastric cancer cell line AGS. We showed that the number of LMP1-positive cells
      decreased gradually with each cell passage when the cells were co-cultured with
      LMP1-negative cells. Time-lapse imaging showed that LMP1-positive cells were
      eliminated from a monolayer of LMP1-negative cells. Furthermore, LMP1-positive
      cells stimulated the proliferation of surrounding LMP1-negative cells, but not
      LMP1-positive cells, via exosome-mediated EGFR activation. Our data indicate that
      LMP1 expression drives cell competition between LMP1-positive and -negative
      cells, affecting the behavior of the cells within gastric tissue.

PMID- 28454118
TI  - Simultaneous exposure to FcgammaR and FcalphaR on monocytes and macrophages
      enhances antitumor activity in vivo.
AB  - Therapeutic antibodies are effective for tumor immunotherapy and exhibit
      prominent clinical effects. All approved antibody therapeutics utilize IgG as the
      molecular format. Antibody-dependent cell-mediated cytotoxicity (ADCC) is a key
      mechanism for tumor cell killing by antibodies. For IgG antibodies, ADCC depends
      on FcgammaR-expressing cells, such as natural killer (NK) cells. However, in
      patients with a high tumor burden, antibody therapeutics may lose efficacy owing
      to exhaustion of FcgammaR-expressing effector cells as well as the inhibitory
      effects of certain FcgammaRs on effector cells. To achieve more potent effector
      functions, we engineered an anti-CD20 antibody to contain both IgG Fc and IgA Fc
      domains. These engineered antibodies interacted with both IgG and IgA Fc
      receptors (FcgammaR and FcalphaR) and recruited a broader range of effector
      cells, including monocytes, macrophages, neutrophils, and NK cells, thereby
      enhancing antibody-dependent cellular phagocytosis. Using transgenic mice
      expressing the FcalphaRI (CD89) in macrophages, we demonstrated that recombinant
      antibodies bearing the chimeric IgG and IgA Fc exhibited potent in vivo antitumor
      activity. Additionally, in a short-term peritoneal model using CD20-transfected
      LLC target cells, the in vivo cytotoxic activity of hybrid recombinant antibodies
      was mediated by macrophages with significant reduction in the absence of
      FcalphaRI. Our findings supported targeting of FcalphaRI on monocytes and
      macrophages for improved tumor immunotherapy.

PMID- 28454119
TI  - Anti-proliferative and anti-secretory effects of everolimus on human pancreatic
      neuroendocrine tumors primary cultures: is there any benefit from combination
      with somatostatin analogs?
AB  - Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
      is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus
      recently obtained approval from the Food and Drug Administration for the
      treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs).
      Despite its promising antitumor efficacy observed in cell lines, clinical benefit
      for patients is unsatisfactory. The limited therapeutic potential of everolimus
      in cancer cells has been attributed to Akt activation due to feedback loops
      relief following mTOR inhibition. Combined inhibition of Akt might then improve
      everolimus antitumoral effect. In this regard, the somatostatin analog (SSA)
      octreotide has been shown to repress the PI3K/Akt pathway in some tumor cell
      lines. Moreover, SSAs are well tolerated and routinely used to reduce symptoms
      caused by peptide release in patients carrying functional GEP-NETs. We have
      recently established and characterized primary cultures of human pNETs and
      demonstrated the anti-proliferative effects of both octreotide and pasireotide.
      In this study, we aim at determining the antitumor efficacy of everolimus alone
      or in combination with the SSAs octreotide and pasireotide in primary cultures of
      pNETs. Everolimus reduced both Chromogranin A secretion and cell viability and
      upregulated Akt activity in single treatment. Its anti-proliferative and anti
      secretory efficacy was not improved combined with the SSAs. Both SSAs did not
      overcome everolimus-induced Akt upregulation. Furthermore, caspase-dependent
      apoptosis induced by SSAs was lost in combined treatments. These molecular events
      provide the first evidence supporting the lack of marked benefit in patients co
      treated with everolimus and SSA.

PMID- 28454120
TI  - Phosphodiesterase 3A: a new player in development of interstitial cells of Cajal
      and a prospective target in gastrointestinal stromal tumors (GIST).
AB  - We previously identified phosphodiesterase 3A (PDE3A) as a marker for
      interstitial cells of Cajal (ICC) in adult mouse gut. However, PDE3A expression
      and function during gut development and in ICC-derived gastrointestinal stromal
      tumors (GIST) remained unknown. Here we found that PDE3A was expressed throughout
      ICC development and that ICC density was halved in PDE3A-deficient mice. In the
      human imatinib-sensitive GIST882 cell line, the PDE3 inhibitor cilostazol halved
      cell viability (IC50 0.35 MUM) and this effect synergized with imatinib (Chou
      Talalay's CI50 0.15). Recently the compound 6-(4-(diethylamino)-3-nitrophenyl)-5
      methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP was found to be cytotoxic
      selectively for cells expressing both PDE3A and Schlafen12 (SLFN12) (de Waal L et
      al. Nat Chem Bio 2016), identifying a new, non-catalytic, role for PDE3A. 108 out
      of 117 (92%) of our human GIST samples displayed both PDE3A and SLFN12
      immunoreactivity. GIST882 cells express both PDE3A and SLFN12 and DNMDP decreased
      their viability by 90%. Our results suggest a role for PDE3A during ICC
      development and open novel perspectives for PDE3A in targeted GIST therapy, on
      one hand by the synergism between imatinib and cilostazol, a PDE3 inhibitor
      already in clinical use for other indications, and, on the other hand, by the
      neomorphic, druggable, PDE3A-SLFN12 cytotoxic interplay.

PMID- 28454123
TI  - Sensitivity and Specificity of the Modified Balance Error Scoring System in
      Concussed Collegiate Student Athletes.
AB  - OBJECTIVE: To assess the efficacy of the modified Balance Error Scoring System
      (mBESS) compared with the Balance Error Scoring System (BESS) in an acutely
      concussed population. DESIGN: Prospective observational study. SETTING:
      University athletic training room. PATIENTS: Thirty-five collegiate student
      athletes (18 Female, 18.9 +/- 0.8 year old, height: 1.71 +/- 0.12 m, weight: 76.3
      +/- 24.1 kg) with diagnosed concussions and baseline BESS/mBESS tests.
      INTERVENTIONS: All participants completed the BESS and mBESS on the day after the
      concussion (acute) and were retested daily until their BESS score achieved
      baseline value (recovery). MAIN OUTCOME MEASURES: The number of errors committed
      during the BESS and mBESS at each time point were recorded. The sensitivity and
      specificity of the BESS and mBESS compared with the baseline test was calculated
      for acute and recovery as well as the mBESS compared with the BESS. RESULTS: At
      acute, the sensitivity of the BESS and mBESS were 60.0% and 71.4%, respectively.
      Relative to mBESS baseline, 60% of participants were misclassified at either
      acute or recovery. CONCLUSIONS: The mBESS had higher sensitivity at acute and
      identified lingering deficits at BESS recovery. Use of the mBESS is likely to
      produce different results than the BESS; however, the clinical implications of
      this warrant further investigation.

PMID- 28454121
TI  - Kruppel-like factor 17 inhibits urokinase plasminogen activator gene expression
      to suppress cell invasion through the Src/p38/ MAPK signaling pathway in human
      lung adenocarcionma.
AB  - Kruppel-like factor 17 (KLF17) has been reported to be involved in invasion and
      metastasis suppression in lung cancer, but the molecular mechanisms underlying
      the anti-invasion and anti-metastasis roles of KLF17 in lung cancer are not fully
      illustrated. Here, we showed that KLF17 inhibited the invasion of A549 and H322
      cells; the anti-invasion effect of KLF17 was associated with the suppression of
      urokinase plasminogen activator (uPA/PLAU) expression. KLF17 can bind with the
      promoter of uPA and inhibit its expression. Enforced expression of uPA abrogated
      the anti-invasion effect of KLF17 in A549 and H322 cells. In addition,
      immunohistochemistry staining showed that the protein expression of KLF17 was
      negatively correlated with that of uPA in archived samples from patients with
      lymph node metastasis of lung adenocarcinoma (rho = -0.62, P = 0.01). The
      mutually exclusive expression of KLF17 with uPA could predict lymph node
      metastasis for lung adenocarcinoma (AUC = 0.758, P = 0.005). Enforced expression
      of KLF17 inhibited the expression of phosphorylated Src and phosphorylated
      p38/MAPK in A549 and H322 cells. The invasiveness of the cells were suppressed by
      treating with sb203580 (p38/MAPK inhibitor) or HY-13805 (PP2, Src inhibitor).
      furthermore, p38/MAPK inhibition could block the KLF17-induced reduction of p
      p38/MAPK and uPA, and Src inhibition enhanced the KLF17-induced suppression of p
      Src and uPA in A549 and H322 cells. In conclusion, our study indicated that KLF17
      suppressed the uPA-mediated invasion of lung adenocarcinoma. The Src and p38/MAPK
      signaling pathways were suggested as mediators of KLF17-induced uPA inhibition,
      thus providing evidence that KLF17 might be a potential anti-invasion candidate
      for lung adenocarcinoma.

PMID- 28454124
TI  - Influence of the rehabilitation outcome on returning to drive after neurological
      impairment.
AB  - In traumatic brain injury (TBI) and stroke rehabilitation, the question of
      reintegration of the driver into traffic is faced very often. Driving is an
      important domain and for some patients, return to driving represents a crucial
      event for community inclusion. The aim of our study was to examine the utility of
      Glasgow Coma Scale within the first 24 h of injury and the Functional
      Independence Measure (FIM) at rehabilitation admission for predicting the return
      to driving. We included 72 patients after TBI or stroke. Driving outcome was
      assessed in terms of being allowed to drive without restrictions as opposed to
      failing the test or being allowed to drive with restrictions. We examined two
      samples: the TBI patients only and the entire sample including patients after
      stroke. The results indicate that for TBI patients, Glasgow Coma Scale and motor
      FIM could be predictors of driving outcome; in the entire sample, the
      unrestricted driving outcome was also associated with a high score on the FIM
      motor scale. Early prediction of return to driving after TBI and stroke is
      important for the patients, their families and the rehabilitation teams to set
      realistic goals that enable the best possible reintegration after rehabilitation.

PMID- 28454122
TI  - Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients
      with advanced pancreatic cancer.
AB  - BACKGROUND: Olaparib is an oral inhibitor of polyadenosine 5'-diphosphoribose
      polymerization (PARP) that has previously shown signs of activity in patients
      with BRCA mutations and pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND
      METHODS: In this phase 1 dose-escalation trial in patients with unresectable
      PDAC, we determined the maximum tolerated dose (MTD) of olaparib (tablet
      formulation) in combination with irinotecan 70 mg/m2 on days 1 and 8 and
      cisplatin 25 mg/m2 on days 1 and 8 of a 28-day cycle (olaparib plus IC). We then
      studied the safety and tolerability of adding mitomycin C 5 mg/m2 on day 1 to
      this regimen (olaparib plus ICM). RESULTS: 18 patients with unresectable PDAC
      were enrolled. The MTD of olaparib plus IC was olaparib 100 mg twice-daily on
      days 1 and 8. The addition of mitomycin C to this dose level was not tolerated.
      Grade >=3 drug-related adverse events (AEs) were encountered in 16 patients
      (89%). The most common grade >=3 drug-related toxicities included neutropenia
      (89%), lymphopenia (72%), and anemia (22%). Two patients (11%), both of whom had
      remained on study for more than 12 cycles, developed drug-related myelodysplastic
      syndrome (MDS). The objective response rate (ORR) for all evaluable patients was
      23%. One patient who carried a deleterious germline BRCA2 mutation had a durable
      clinical response lasting more than four years, but died from complications of
      treatment-related MDS. CONCLUSIONS: Olaparib had substantial toxicity when
      combined with IC or ICM in patients with PDAC, and this treatment combination did
      not have an acceptable risk/benefit profile for further study. However, durable
      clinical responses were observed in a subset of patients and further clinical
      investigation of PARP inhibitors in PDAC is warranted. TRIAL REGISTRATION: This
      clinical trial was registered on ClinicalTrials.gov as NCT01296763.

PMID- 28454125
TI  - Polarization-dependent intermodal four-wave mixing in a birefringent multimode
      photonic crystal fiber.
AB  - In this Letter, polarization-dependent intermodal four-wave mixing (FWM) is
      demonstrated experimentally in a birefringent multimode photonic crystal fiber
      (BM-PCF) designed and fabricated in-house. Femtosecond pump pulses at wavelengths
      ~800  nm polarized along one of the principal axes of the BM-PCF are coupled into
      a normal dispersion region away from the zero-dispersion wavelengths of the
      fundamental guided mode of the BM-PCF. Anti-Stokes and Stokes waves are generated
      in the 2nd guided mode at visible and near-infrared wavelengths, respectively.
      For pump pulses at an average input power of 500 mW polarized along the slow
      axis, the conversion efficiencies eta<sub>as</sub> and eta<sub>s</sub> of the
      anti-Stokes and Stokes waves generated at wavelengths 579.7 and 1290.4 nm are 19%
      and 14%, respectively. For pump pulses polarized along the fast axis, the
      corresponding eta<sub>as</sub> and eta<sub>s</sub> at 530.4 and 1627 nm are 23%
      and 18%, respectively. We also observed that fiber bending and intermodal walk
      off have a small effect on the polarization-dependent intermodal FWM-based
      frequency conversion process.

PMID- 28454126
TI  - Stabilized microwave-frequency transfer using optical phase sensing and
      actuation.
AB  - We present a stabilized microwave-frequency transfer technique that is based on
      optical phase sensing and optical phase actuation. This technique shares several
      attributes with optical-frequency transfer and, therefore, exhibits several
      advantages over other microwave-frequency transfer techniques. We demonstrated
      the stabilized transfer of an 8000 MHz microwave-frequency signal over a 166 km
      metropolitan optical fiber network, achieving a fractional frequency stability of
      6.8*10<sup>-14</sup>  Hz/Hz at 1 s integration and 5.0*10<sup>-16</sup>  Hz/Hz at
      1.6*10<sup>4</sup>  s. This technique is being considered for use on the Square
      Kilometre Array SKA1-mid radio telescope.

PMID- 28454128
TI  - 2.3-MUm Tm<sup>3+</sup>:YLF laser passively Q-switched with a
      Cr<sup>2+</sup>:ZnSe saturable absorber.
AB  - We report, what is to our knowledge, the first passively Q-switched operation of
      a 2.3-MUm Tm<sup>3+</sup>:YLF laser by using a Cr<sup>2+</sup>:ZnSe saturable
      absorber. In the experiments, a tunable Ti<sup>3+</sup>:sapphire laser was used
      to end pump the Tm<sup>3+</sup>:YLF gain medium inside an x cavity. A
      Cr<sup>2+</sup>:ZnSe saturable absorber was also included in the cavity to
      initiate passive Q switching. At all pump power levels above lasing threshold,
      passively Q-switched operation of the Tm<sup>3+</sup>:YLF laser could be obtained
      at 2309 nm with pulse durations and repetition frequencies in the ranges of 1.2
      1.4 MUs and 0.3-2.1 kHz, respectively. Analysis of power dependent repetition
      rate data further gave an estimated value of 3.1% for the round-trip saturable
      loss of the Cr<sup>2+</sup>:ZnSe saturable absorber.

PMID- 28454127
TI  - Sn-based waveguide p-i-n photodetector with strained GeSn/Ge multiple-quantum
      well active layer.
AB  - We report on Sn-based p-i-n waveguide photodetectors (WGPD) with a pseudomorphic
      GeSn/Ge multiple-quantum-well (MQW) active layer on a Ge-buffered Si substrate. A
      reduced dark-current density of 59  mA/cm<sup>2</sup> was obtained at a reverse
      bias of 1 V due to the suppressed strain relaxation in the GeSn/Ge active layer.
      Responsivity experiments revealed an extended photodetection range covering the
      O, E, S, C, and L telecommunication bands completely due to the bandgap reduction
      resulting from Sn-alloying. Band structure analysis of the pseudomorphic GeSn/Ge
      quantum well structures indicated that, despite the stronger quantum confinement,
      the absorption edge can be shifted to longer wavelengths by increasing the Sn
      content, thereby enabling efficient photodetection in the infrared region. These
      results demonstrate the feasibility of using GeSn/Ge MQW planar photodetectors as
      building blocks of electronic-photonic integrated circuits for telecommunication
      and optical interconnection applications.

PMID- 28454129
TI  - Photostability of pulsed-laser-deposited As<sub>x</sub>Te<sub>100-x</sub> (x=40,
      50, 60) amorphous thin films.
AB  - As<sub>x</sub>Te<sub>100-x</sub> amorphous thin films were fabricated by a pulsed
      laser deposition technique with the aim of finding photostable layers in as
      deposited but preferably in relaxed (annealed) state. Photostability was studied
      in terms of the films' stability of refractive index and bandgap under near
      bandgap light irradiation. As<sub>40</sub>Te<sub>60</sub> and
      As<sub>50</sub>Te<sub>50</sub> layers were found to be photostable in both as
      deposited as well as relaxed states. Moreover, As<sub>50</sub>Te<sub>50</sub>
      layers present the lowest surface roughness. These characteristics make pulsed
      laser-deposited As<sub>50</sub>Te<sub>50</sub> thin films promising for
      applications in nonlinear optics.

PMID- 28454130
TI  - Directly modulated green-light diode-pumped solid-state laser for underwater
      wireless optical communication.
AB  - It is widely known that a diode-pumped solid-state laser (DPSSL) has very limited
      modulation bandwidth. Recently, we directed our attention toward the
      opportunities for directly modulating a DPSSL to generate high-speed green-light
      signals, with high power and superior beam quality, which are highly desirable in
      underwater wireless optical communication. The constraint imposed by the limited
      modulation bandwidth of a DPSSL is circumvented with the strategy of orthogonal
      frequency-division multiplexing and power loading. With a compact DPSSL
      dismantled from a low-cost laser pointer, we achieve net bit rates of 108.55 Mb/s
      for the 64 quadrature amplitude modulation (QAM) signal at a bit error rate (BER)
      of 6.42*10<sup>-4</sup> and 89.55 Mb/s for the 32 QAM signal at a BER of
      4.81*10<sup>-4</sup>, respectively, over a 2 m underwater channel. When the
      underwater transmission distance is increased to 6 m, the BERs are still below
      the forward error correction (FEC) limit of 3.8*10<sup>-3</sup>.

PMID- 28454131
TI  - Uni-directional wavelength conversion in silicon using four-wave mixing driven by
      cross-polarized pumps.
AB  - We demonstrate optical frequency conversion between telecom wavelengths using
      four-wave mixing Bragg scattering powered by two pump pulses polarized on
      orthogonal axes of a silicon waveguide. This allows conversion in a single
      frequency direction while, with co-polarized pumps, the signal is redshifted or
      blueshifted with similar efficiency. Our approach exploits the birefringence of
      the waveguide and its effect on the phase matching of the four-wave mixing
      process. The blue or red direction can be selected by the input polarization of
      the signal, and 20 dB extinction ratios are observed with the unintended
      direction. This technique will allow efficient and controlled conversion between
      specified wavelength channels in integrated photonic devices.

PMID- 28454132
TI  - Broadband single-mode single-polarization passive fully aperiodic large-pitch
      fibers.
AB  - Two evolutions of fully aperiodic large-pitch fiber designs employing few stress
      applying parts are presented. The induced elasto-optic stress discriminates the
      two orthogonal polarization modes (LP<sub>01x</sub> and LP<sub>01y</sub>) of the
      fundamental mode, selectively delocalizing one of them into the cladding via a
      suitable coupling to one or several cladding modes. This ensures the propagation
      of a single linear polarization mode. For the largest core dimensions, however,
      the applied stress can strongly influence the intensity distributions of core
      modes, and a tailored design process must thwart this. The polarization
      properties are investigated experimentally with core scalability over a large
      spectral bandwidth into passive structures, leading to the evidencing of a single
      mode single polarization over a large span from 1 to 1.6 MUm with a core
      dimension of 80 MUm and, notably, at 1400 nm for a core dimension of 140 MUm. The
      polarization extinction ratio is also determined.

PMID- 28454133
TI  - Aperture scalable, high-average power capable, hybrid-electrode Pockels cell.
AB  - We demonstrate a hybrid-electrode Pockels cell (HEPC) using a thin z-cut
      deuterated potassium dihydrogen phosphate (DKDP) crystal. The device is a
      reflective, longitudinally driven, longitudinally cooled Pockels cell,
      constructed with a plasma chamber providing the incident-side electrode and a
      silicon-substrate mirror serving the three purposes of a mirror, a back-side
      electrode, and a heat sink. The mirror and the DKDP are thermally coupled through
      a sub-millimeter, inert gas-filled gap. A time-multiplex pass-by driving method
      is proposed to favor low-voltage and fast-response operation. The experimental
      results support that the HEPC would be a competent device for high-energy and
      high-repetition-rate lasers.

PMID- 28454134
TI  - Self-stabilization of an optical frequency comb using a short-path-length
      interferometer.
AB  - We stabilized the repetition rate of an optical frequency comb using a self
      referenced phase-locked loop. The phase-locked loop generated its error signal
      with a fiber-optic delay-line interferometer that had a path-length difference of
      8 m. We used the stabilized repetition rate to generate a 10 GHz signal with a
      single-sideband phase noise that was limited by environmental noise to -120 
      dBc/Hz at an offset frequency of 1 kHz. Modeling results indicate that
      thermoconductive noise sets a fundamental phase noise limit for an 8 m
      interferometer of -152  dBc/Hz at a 1 kHz offset frequency. The short length of
      the interferometer indicates that it could be realized as a photonic integrated
      circuit, which may lead to a chip-scale stabilized optical frequency comb with an
      ultralow-phase-noise repetition rate.

PMID- 28454135
TI  - Fiber surface Bragg grating waveguide for refractive index measurements.
AB  - A fiber surface Bragg grating waveguide (BGW) fabricated in the surface of single
      mode fiber by direct femtosecond laser inscription is demonstrated and
      successfully applied for refractive index (RI) measurements. Prior to laser
      inscription of the fiber surface BGW, an X-coupler is first inscribed across the
      fiber core to couple light from the core to the fiber surface. The light
      transmitted in the fiber surface BGW efficiently interacts with the surrounding
      medium due to a strong evanescent field, and obtains an acceptable RI sensitivity
      approaching ~16  nm/RIU. The novel design efficiently couples the light guided in
      the core with the surrounding medium using a non-destructive, single-step
      micromachining process, and is expected to have potential applications in fiber
      biochemical sensing.

PMID- 28454136
TI  - Laser writing of nonlinear optical properties in silver-doped phosphate glass.
AB  - The formation of both local second- and third-harmonic generations (SHG and THG)
      induced by a train of femtosecond laser pulses in silver-doped phosphate glasses
      is addressed. Based on modeling calculations, including various diffusion and
      kinetic processes, THG is shown to result from the formation of silver clusters.
      The latter organize into a ring-shape structure, leading to the emergence of a
      static electric field. By breaking the glass centro-symmetry, this field gives
      rise to a local effective second-order susceptibility, inducing SHG. Both
      theoretically predicted SHG and THG evolutions with respect to the number of
      pulses in the train are in good agreement with experimental observations. In
      particular, the observed reaching of a maximum in the nonlinear optical responses
      after a few thousands of pulses is explained by the competition of various
      physical processes. A cooling of the glass is shown to improve the process
      efficiency of the laser writing of second-order nonlinearity.

PMID- 28454137
TI  - Dynamic Stark shift induced by a single photon packet.
AB  - The dynamic Stark shift results from the interaction of an atom with the
      electromagnetic field. We show how a propagating single-photon wave packet can
      induce a time-dependent dynamical Stark shift on a two-level system (TLS). A non
      perturbative fully quantum treatment is employed, where the quantum dynamics of
      both the field and the TLS are analyzed. We also provide the means to
      experimentally access such time-dependent frequency by measuring the interference
      pattern in the electromagnetic field inside a 1D waveguide. The effect we
      evidence here may find applications in the autonomous quantum control of quantum
      systems without classical external fields, which can be useful for quantum
      information processing as well as for quantum thermodynamical tasks.

PMID- 28454138
TI  - Programmable single-pixel-based broadband stimulated Raman scattering.
AB  - We report a simple add-on for broadband stimulated Raman scattering (SRS)
      microscopes to enable fast and programmable spectroscopy acquisition. It
      comprises a conventional dispersive spectrometer layout incorporating a fast
      digital micromirror device (DMD). The approach is validated by acquiring SRS
      spectra of standard chemicals. We demonstrate a DMD's advantage in broadband SRS
      by showing higher signal-to-noise ratio using a multiplexed Hadamard spectral
      basis and compressive sensing detection. Our results apply to a variety of
      frequency-domain pump-probe spectroscopy.

PMID- 28454139
TI  - Blueshift and phase tunability in planar THz metamaterials: the role of losses
      and toroidal dipole contribution.
AB  - We propose a model of tunable THz metamaterials. The main advantage is the
      blueshift of resonance and phase tunability due to inductive coupling in planar
      metallic metamolecules with incorporated silicon wires. We discuss the role of
      losses and toroidal dipole contribution to metamaterial response.

PMID- 28454140
TI  - Electro-optic sampling of terahertz waves by laser pulses with an edge-cut
      spectrum in birefringent crystal.
AB  - We demonstrate a terahertz detection technique based on variations of the energy
      of femtosecond laser pulses with an edge-cut spectrum in birefringent electro
      optic crystal-periodically poled lithium niobate (PPLN). The method is compared
      with the standard electro-optic detection scheme utilizing GaP crystal. The
      experimental results show that the studied technique is suited for use with
      birefringent crystals and allows one to achieve a much better response to the
      terahertz wave radiation at quasi-phase-matching frequencies of PPLN.

PMID- 28454141
TI  - Incoherent optical modulation of graphene based on an in-line fiber Mach-Zehnder
      interferometer.
AB  - We investigated the incoherent optical modulation of graphene based on an in-line
      fiber Mach-Zehnder interferometer fabricated by offset splicing of a D-shaped
      fiber and single-mode fibers. The D-shaped flat surface was coated with a single
      layer graphene whose refractive index can be modulated by an external laser. With
      a backward pump-probe setup, we found that the incoherent optical modulation
      occurred independently of the wavelength difference between the pump and probe
      lasers, supporting the theoretical analysis that the incoherent optical
      modulation is mainly contributed by the carrier-phonon process of graphene.
      Further, both the decrease of the pump wavelength and the increase of the pump
      power would deepen the modulation in an exponential trend. The experimental
      results are beneficial to understanding the incoherent optical modulation process
      in graphene. The proposed interferometer covered by graphene can also be used as
      a compact all-optical intensity modulator.

PMID- 28454142
TI  - In situ SERS monitoring of plasmonic nano-dopants during photopolymerization.
AB  - The motion of the plasmonic nano-dopant in photopolymers was monitored in situ
      and in real time using the surface-enhanced Raman scattering (SERS) technique.
      Here an Au@MBA@Ag (core-molecule-shell) nanoparticle colloid was synthesized to
      act as the nano-dopant and adsorbed 4-mercaptobenzoic acid (MBA) between the Au
      cells and Ag shells as the internal standard. The changes of the MBA signal
      closely reflect the motion of nanoparticles, since the MBA signal itself has time
      stability. Experimental data indicate that the optimized concentration of the
      nano-dopant can be obtained based on the peak intensity change of MBA at 1583 
      cm<sup>-1</sup>. This Letter provides a novel way for in situ monitoring of
      photophysicial and photochemical processes.

PMID- 28454143
TI  - Nondestructive distributed measurement of supercontinuum generation along highly
      nonlinear optical fibers.
AB  - Supercontinuum generation (SCG) in optical fibers arises from the spectral
      broadening of an intense light, which results from the interplay of both linear
      and nonlinear optical effects. In this Letter, a nondestructive optical time
      domain reflectometry method is proposed for the first time, to the best of our
      knowledge, to measure the spatial (longitudinal) evolution of the SC induced
      along an optical fiber. The method was experimentally tested on highly nonlinear
      fibers. The experimental results are in a good agreement with the optical spectra
      measured at the fiber outputs.

PMID- 28454144
TI  - Automatic focusing for multisectional objects in digital holography using the
      structure tensor.
AB  - Determining the axial position of the recorded object in digital holography is a
      crucial step for image reconstruction. When multiple discrete sections of a three
      dimensional object are overlapping each other, this issue becomes more
      challenging. In this Letter, an autofocusing algorithm using the structure tensor
      and its eigenvalues is proposed. This method can extract the focal distance of
      each section for a multi-sectional object irrespective of whether the sections
      are overlapping or not. We validate the applicability of the proposed technique
      with synthesized and experimental data using two types of holographic systems.

PMID- 28454145
TI  - Yb<sup>3+</sup>-doped CaF<sub>2</sub>-LaF<sub>3</sub> ceramics laser.
AB  - Highly transparent ceramic is an attractive gain medium for high-power lasers due
      to its high fracture toughness, homogeneity, and size scalability. Here we report
      the first Yb<sup>3+</sup>-doped CaF<sub>2</sub>-LaF<sub>3</sub> ceramics laser.
      Codoping of La<sup>3+</sup> ion can reduce the formation of Yb<sup>2+</sup> ions
      and enhance the laser efficiency. In the laser experiment, the maximum output
      power of 4.36 W and the maximum slope efficiency of 69.5% were obtained with a 3%
      La, 2% Yb sample and a 2% La, 1% Yb sample, respectively. Due to the combined
      properties of Yb:CaF<sub>2</sub> and a ceramic laser gain medium,
      Yb:CaF<sub>2</sub>-LaF<sub>3</sub> ceramic is a promising gain medium for a high
      power ultrashort pulse laser and amplifier.

PMID- 28454146
TI  - SNR enhancement in high-resolution phase-sensitive OTDR systems using chirped
      pulse amplification concepts.
AB  - Phase-sensitive optical time-domain reflectometry (phiOTDR) is widely used for
      the distributed detection of mechanical or environmental variations with
      resolutions of typically a few meters. The spatial resolution of these
      distributed sensors is related to the temporal width of the input probe pulses.
      However, the input pulse width cannot be arbitrarily reduced (to improve the
      resolution), since a minimum pulse energy is required to achieve a good level of
      signal-to-noise ratio (SNR), and the pulse peak power is limited by the advent of
      nonlinear effects. In this Letter, inspired by chirped pulse amplification
      concepts, we present a novel technique that allows us to increase the SNR by
      several orders of magnitude in phiOTDR-based sensors while reaching spatial
      resolutions in the centimeter range. In particular, we report an SNR increase of
      20 dB over the traditional architecture, which is able to detect strain events
      with a spatial resolution of 1.8 cm.

PMID- 28454147
TI  - Layout of NALM fiber laser with adjustable peak power of generated pulses.
AB  - The Letter proposes a new layout of a passively mode-locked fiber laser based on
      a nonlinear amplifying loop mirror (NALM) with two stretches of active fiber and
      two independently controlled pump modules. In contrast with conventional NALM
      configurations using a single piece of active fiber that yields virtually
      constant peak power, the proposed novel laser features larger than a factor of 2
      adjustment range of peak power of generated pulses. The proposed layout also
      provides independent adjustment of duration and peak power of generated pulses as
      well as power-independent control of generated pulse spectral width impossible in
      NALM lasers with a single piece of active fiber.

PMID- 28454148
TI  - Highly efficient graphene-on-gap modulator by employing the hybrid plasmonic
      effect.
AB  - We propose a highly efficient graphene-on-gap modulator (GOGM) by employing the
      hybrid plasmonic effect, whose modulation efficiency (up to 1.23 dB/MUm after
      optimization) is ~12-fold larger than that of the present graphene-on-silicon
      modulator (~0.1  dB/MUm). The proposed modulator has the advantage of a short
      modulation length of ~3.6  MUm, a relatively low insertion loss of ~0.32  dB, and
      a larger modulation bandwidth of ~0.48  THz. The physical insight is
      investigated, showing that both the slow light effect and the overlap between
      graphene and the mode field contribute. Moreover, an efficient taper coupler has
      been designed to convert the quasi-transverse electric mode of conventional
      silicon waveguide to the hybrid plasmonic mode of GOGM, with a high coupling
      efficiency of 91%. This Letter may promote the design of high-performance on-chip
      electro-optical modulators.

PMID- 28454149
TI  - Radially and azimuthally polarized nanosecond Yb-doped fiber MOPA system
      incorporating temporal shaping.
AB  - We report an Yb-doped fiber master-oscillator power-amplifier (MOPA) system with
      the capability of selectively generating doughnut-shaped radially and azimuthally
      polarized beams with user-defined temporal pulse shapes. The desired output
      polarization was generated with the aid of a nanograting spatially variant half
      waveplate (S-waveplate). The latter was used to convert the linearly polarized
      fundamental (LP<sub>01</sub>) mode output from the preamplification stages to a
      doughnut-shaped radially polarized beam prior to the power amplifier stage. A
      maximum output pulse energy of ~860  MUJ was achieved for ~100  ns pulses at 25
      kHz with user-defined pulse shape for both radial and azimuthal polarization
      states. The polarization purity and beam propagation factor (M<sup>2</sup>) were
      measured to be >12  dB and 2.2, respectively.

PMID- 28454150
TI  - Selective propagation and beam splitting of surface plasmons on metallic nanodisk
      chains.
AB  - Manipulating the propagation of surface plasmons (SPs) on a nanoscale is a
      fundamental issue of nanophotonics. By using focused electron beam, SPs can be
      excited with high spatial accuracy. Here we report on the propagation of SPs on a
      chain of gold nanodisks with cathodoluminescence (CL) spectroscopy. Experimental
      evidence for the propagation of SPs excited by the focused electron beam is
      demonstrated. The wavelength of the transmitted SPs depends on the geometrical
      parameters of the nanodisk chain. Furthermore, we design and fabricate a beam
      splitter, which selectively transmits SPs of certain wavelengths to a specific
      direction. By scanning the sample surface point by point and collecting the CL
      spectra, we obtain the spectral mapping and identify that the chain of the
      smaller nanodisks can efficiently transport SPs at shorter wavelengths. This
      Letter provides a unique approach to manipulate in-plane propagation of SPs.

PMID- 28454151
TI  - High-power frequency comb source tunable from 2.7 to 4.2  MUm based on difference
      frequency generation pumped by an Yb-doped fiber laser.
AB  - We demonstrate a broadband mid-infrared (MIR) frequency comb source based on
      difference frequency generation (DFG) in periodically poled lithium niobate
      crystal. MIR radiation is obtained via mixing of the output of a 125 MHz
      repetition rate Yb-doped fiber laser with Raman-shifted solitons generated from
      the same source in a highly nonlinear fiber. The resulting idler is tunable in
      the range of 2.7-4.2 MUm, with average output power reaching 237 mW and pulses as
      short as 115 fs. The coherence of the MIR comb is confirmed by spectral
      interferometry and heterodyne beat measurements. Applicability of the developed
      DFG source for laser spectroscopy is demonstrated by measuring absorption
      spectrum of acetylene at 3.0-3.1 MUm.

PMID- 28454152
TI  - 88% conversion efficiency with an atomic spin wave mediated mode selection.
AB  - In studying quantum correlation and quantum memory of continuous variables of
      light fields and atoms, a crucial step is the retrieval of the quantum fields by
      converting an atomic spin wave to light, and retrieval efficiency is a crucial
      parameter. In this Letter, we implement a double-pass Raman scheme in Rb87 by
      incorporating coherent feedback. We find that the transfer efficiency from an
      atomic spin wave, which is generated from a Raman process in a high gain regime,
      to light fields is enhanced by the double-pass scheme as compared to the commonly
      used single-pass scheme. An atomic spin wave as high as 88% is read out, limited
      only by decoherence of the atomic spin waves. Our analysis shows that the
      enhancement effect is because a double-pass scheme introduced the coherent
      feedback mechanism which selects the spatial mode of an atomic spin wave via the
      correlated optical field and enhances the coupling efficiency between the atom
      and light. The correlations between the write-in and readout signals generated in
      such a two-pass Raman process are also better than the single-pass case. We
      believe such a two-pass scheme with feedback mechanism should be useful for
      studying continuous variables in quantum systems.

PMID- 28454153
TI  - Akhmediev breathers and Peregrine solitary waves in a quadratic medium.
AB  - I investigate the formation of optical localized nonlinear structures, evolving
      upon a non-zero background plane wave in a dispersive quadratic medium. I show
      the existence of quadratic Akhmediev breathers and Peregrine solitary waves in
      the regime of cascading second-harmonic generation. This finding opens a novel
      path for the excitation of extreme rogue waves and for the description of
      modulation instability in quadratic nonlinear optics.

PMID- 28454154
TI  - Photoacoustic imaging of dental implants in a porcine jawbone ex vivo.
AB  - Currently, x-ray-based imaging is used before and after the dental implant
      treatment, but the ionizing radiation is potentially harmful to patients and
      operators. Here, we demonstrate ex vivo photoacoustic imaging of a dental implant
      embedded in a porcine jawbone. By layering biological tissue over the jawbone to
      mimic a clinical environment, we demonstrate 10 mm deep imaging. Our results show
      that photoacoustic imaging can provide jawbone anatomical information, the
      location of an embedded implant fixture, and the thickness of the soft tissue
      above the jawbone.

PMID- 28454155
TI  - Efficient terahertz anti-reflection properties of metallic anti-dot structures.
AB  - We report the use of micrometer-sized copper (Cu) anti-dot structures as a novel
      terahertz (THz) anti-reflection coating (ARC) material and their superior
      performance over conventionally used metallic (Cu) thin films. Cu anti-dot
      structures of two different thicknesses (7 and 10 nm) with varying anti-dot
      diameters (100, 200, and 300 MUm, inter-anti-dot separation fixed at 100 MUm) are
      deposited on silicon substrates by RF magnetron sputtering and e-beam
      evaporation. The anti-reflection performance of these samples is studied in the
      frequency range of 0.3-2.2 THz. While continuous metallic (Cu) thin film
      minimizes the Fabry-Perot (FP) peak, it also suppresses the primary transmission
      peak, reducing the advantage due to the former effect. On the contrary, the anti
      dot arrays reduce both the absolute amplitude of the FP peak and the amplitude
      ratio (AR) of the FP peak to the primary peak, making them a superior material
      for ARC applications. The AR can be further manipulated by varying the anti-dot
      size. A universal conductivity phase-matching condition, which is a prerequisite
      for the disappearance of the FP peak, is observed in these samples. The enhanced
      anti-reflection performance promotes these anti-dot structures as an efficient
      terahertz ARC material.

PMID- 28454156
TI  - Continuously wavelength-tunable high harmonic generation via soliton dynamics.
AB  - We report the generation of high harmonics in a gas jet pumped by pulses self
      compressed in a He-filled hollow-core photonic crystal fiber through the soliton
      effect. The gas jet is placed directly at the fiber output. As the energy
      increases, the ionization-induced soliton blueshift is transferred to the high
      harmonics, leading to emission bands that are continuously tunable from 17 to 45
      eV.

PMID- 28454157
TI  - Wavelength division multiplexed light source monolithically integrated on a
      silicon photonics platform.
AB  - We demonstrate monolithic integration of a wavelength division multiplexed light
      source for silicon photonics by a cascade of erbium-doped aluminum oxide
      (Al2O3:Er3+) distributed feedback (DFB) lasers. Four DFB lasers with uniformly
      spaced emission wavelengths are cascaded in a series to simultaneously operate
      with no additional tuning required. A total output power of -10.9  dBm is
      obtained from the four DFBs with an average side mode suppression ratio of 38.1+/
      2.5  dB. We characterize the temperature-dependent wavelength shift of the
      cascaded DFBs and observe a uniform dlambda/dT of 0.02 nm/ degrees C across all
      four lasers.

PMID- 28454158
TI  - Adding a spin to Kerker's condition: angular tuning of directional scattering
      with designed excitation.
AB  - We describe a method to control the directional scattering of a high-index
      dielectric nanosphere, which utilizes the unique focusing properties of an
      azimuthally polarized phase vortex and a radially polarized beam to independently
      excite inside the nanosphere a spinning magnetic dipole and a linearly polarized
      electric dipole mode normal to the magnetic dipole. We show that by simply
      adjusting the phase and amplitude of the field on the exit pupil of the optical
      system, the scattering of the nanosphere can be tuned to any direction within a
      plane, and the method works over a broad wavelength range.

PMID- 28454159
TI  - Modal interferometer based on a single mechanically induced long-period fiber
      grating and a nanoparticles-coated film section.
AB  - A modal interferometer by a single mechanically induced long-period fiber grating
      (MI-LPFG) using a half-length coating fiber is presented. The coating material
      used for this Letter is a film of silica nanoparticles doped with an organic
      chromophore. The silica nanoparticles, with diameters within the range of 40-50
      nm, were deposited over 3.5 cm length of fiber by the dip-coating method, forming
      a film with a thickness between 500 and 1250 nm. Then the modal interferometer
      was implemented by inscribing the MI-LPFG over the coated fiber section and a
      similar fiber length of the uncoated fiber. The experimental results show high
      contrast transmission bands, where the position and depth of the absorption
      envelope band are finely selected by the grating period, the pressure applied,
      and the film thickness. The novel modal interferometer architecture based on a
      single MI-LPFG, combined with a functionalized nanoparticles coating film, offers
      an attractive platform for the development of fiber sensors and other fiber-based
      devices.

PMID- 28454160
TI  - Spectral selectivity in optical fiber capillary dye lasers.
AB  - We explore the spectral properties of a capillary dye laser in the highly
      multimode regime. Our experiments indicate that the spectral behavior of the
      laser does not conform to a simple Fabry-Perot (FP) analysis; rather, it is
      strongly dictated by a Vernier resonant mechanism involving multiple modes, which
      propagate with different group velocities. The laser operates over a very broad
      spectral range and the Vernier effect gives rise to a free spectral range, which
      is orders of magnitude larger than that expected from a simple FP mechanism. The
      theoretical calculations presented confirm the experimental results. Propagating
      modes of the capillary fiber are calculated using the finite-element method and
      it is shown that the optical path lengths resulting from simultaneous beatings of
      these modes are in close agreement with the optical path lengths directly
      extracted from the Fourier transform of the experimentally measured laser
      emission spectra.

PMID- 28454161
TI  - Correlation and squeezing for optical transistor and intensity router
      applications in diamond NV center.
AB  - We study an optical transistor (switch and amplifier) and router by spontaneous
      parametric four-wave mixing and fluorescence in diamond nitrogen-vacancy (NV)
      center. The routing results from three peaks of fluorescence signal in the time
      domain, while the switching and amplification are realized by correlation and
      squeezing. The intensity switching speed is about 17 ns. The optical transistor
      and router are controlled by the power of incident beams. Our experimental
      results provide that the advance technique of peak division and channel
      equalization ratio of about 90% are applicable to all optical switching and
      routing.

PMID- 28454162
TI  - Three-dimensional electromagnetic Gaussian Schell-model sources.
AB  - We introduce three-dimensional (3D) stationary, electromagnetic Gaussian Schell
      model (GSM) sources in the space-frequency domain and derive the realizability
      conditions that the source parameters must obey. In particular, we extend to 3D
      GSM sources two approaches to the realizability conditions presented previously
      for beam-like GSM sources. The results are of interest in the analysis and
      synthesis of tunable non-paraxial, partially coherent, partially polarized light
      fields.

PMID- 28454163
TI  - Image recovery from defocused 2D fluorescent images in multimodal digital
      holographic microscopy.
AB  - A technique of three-dimensional (3D) intensity retrieval from defocused, two
      dimensional (2D) fluorescent images in the multimodal digital holographic
      microscopy (DHM) is proposed. In the multimodal DHM, 3D phase and 2D fluorescence
      distributions are obtained simultaneously by an integrated system of an off-axis
      DHM and a conventional epifluorescence microscopy, respectively. This gives us
      more information of the target; however, defocused fluorescent images are
      observed due to the short depth of field. In this Letter, we propose a method to
      recover the defocused images based on the phase compensation and backpropagation
      from the defocused plane to the focused plane using the distance information that
      is obtained from a 3D phase distribution. By applying Zernike polynomial phase
      correction, we brought back the fluorescence intensity to the focused imaging
      planes. The experimental demonstration using fluorescent beads is presented, and
      the expected applications are suggested.

PMID- 28454164
TI  - Multiple-wavelength distributed-feedback laser arrays with high coupling
      coefficients and precise channel spacing.
AB  - Special designs of sampled Bragg gratings have been used to fabricate distributed
      feedback semiconductor laser arrays with very precise wavelength spacing and
      strong coupling coefficients. By dividing one sampling period into two equal
      sections, each with a grating but with a pi-phase shift between the sections, the
      +/-1st-order channels are enhanced while eliminating the zeroth-order reflection.
      By using multiple phase-shifted sections, only the -1st-order channel is
      enhanced. Using a single electron beam lithography step and two pi-phase-shifted
      sections, we have fabricated an eight-channel laser array with a channel spacing
      of 100 GHz.

PMID- 28454165
TI  - Light field endoscopy and its parametric description.
AB  - In this Letter, we demonstrate the application of light field imaging to
      endoscopy. By introducing a microlens array into the image plane of a
      conventional endoscope, the 4D light field can be captured in one snapshot. This
      information can be used to obtain perspective images and to digitally refocus to
      different planes. These features allow for the recovery of 3D information in
      minimally invasive surgery. Important optical setup and performance parameters
      are derived to enable task specific engineering of the light field imaging
      system.

PMID- 28454166
TI  - Fabrication of multipoint side-firing optical fiber by laser micro-ablation.
AB  - A multipoint, side-firing design enables an optical fiber to output light at
      multiple desired locations along the fiber body. This provides advantages over
      traditional end-to-end fibers, especially in applications requiring fiber bundles
      such as brain stimulation or remote sensing. This Letter demonstrates that
      continuous wave (CW) laser micro-ablation can controllably create conical-shaped
      cavities, or side windows, for outputting light. The dimensions of these cavities
      determine the amount of firing light and their firing angle. Experimental data
      show that a single side window on a 730 MUm fiber can deliver more than 8% of the
      input light. This can be increased to more than 19% on a 65 MUm fiber with side
      windows created using femtosecond laser ablation and chemical etching. Fine
      control of light distribution along an optical fiber is critical for various
      biomedical applications such as light-activated drug-release and optogenetics
      studies.

PMID- 28454167
TI  - Nanofilm-induced spectral tuning of third harmonic generation.
AB  - Intermodal third-harmonic generation using waveguides is an effective frequency
      conversion process due to the combination of long interaction lengths and strong
      modal confinement. Here we introduce the concept of tuning the third harmonic
      phase-matching condition via the use of dielectric nanofilms located on an open
      waveguide core. We experimentally demonstrate that tantalum oxide nanofilms
      coated onto the core of an exposed core fiber allow tuning the third harmonic
      wavelength over 30 nm, as confirmed by qualitative simulations. Due to its
      generic character, the presented tuning scheme can be applied to any form of
      exposed core waveguide and will find applications in fields including microscopy,
      biosensing, and quantum optics.

PMID- 28454169
TI  - Speckle-based hyperspectral imaging combining multiple scattering and compressive
      sensing in nanowire mats.
AB  - Encoding of spectral information onto monochrome imaging cameras is of interest
      for wavelength multiplexing and hyperspectral imaging applications. Here, the
      complex spatiospectral response of a disordered material is used to demonstrate
      retrieval of a number of discrete wavelengths over a wide spectral range. Strong,
      diffuse light scattering in a semiconductor nanowire mat is used to achieve a
      highly compact spectrometer of micrometer thickness, transforming different
      wavelengths into distinct speckle patterns with nanometer sensitivity. Spatial
      multiplexing is achieved through the use of a microlens array, allowing
      simultaneous imaging of many speckles, ultimately limited by the size of the
      diffuse spot area. The performance of different information retrieval algorithms
      is compared. A compressive sensing algorithm exhibits efficient reconstruction
      capability in noisy environments and with only a few measurements.

PMID- 28454168
TI  - Laser waveform control of extreme ultraviolet high harmonics from solids.
AB  - Solid-state high-harmonic sources offer the possibility of compact, high
      repetition-rate attosecond light emitters. However, the time structure of high
      harmonics must be characterized at the sub-cycle level. We use strong two-cycle
      laser pulses to directly control the time-dependent nonlinear current in single
      crystal MgO, leading to the generation of extreme ultraviolet harmonics. We find
      that harmonics are delayed with respect to each other, yielding an atto-chirp,
      the value of which depends on the laser field strength. Our results provide the
      foundation for attosecond pulse metrology based on solid-state harmonics and a
      new approach to studying sub-cycle dynamics in solids.

PMID- 28454171
TI  - Depth resolution enhancement of terahertz deconvolution by autoregressive
      spectral extrapolation.
AB  - This Letter presents a method for enhancing the depth resolution of terahertz
      deconvolution based on autoregressive (AR) spectral extrapolation. The terahertz
      frequency components with a high signal-to-noise ratio (SNR) are modeled with an
      AR process, and the missing frequency components in the regions with low SNRs are
      extrapolated based on the AR model. In this way, the entire terahertz frequency
      spectrum of the impulse response function, corresponding to the material
      structure, is recovered. This method, which is verified numerically and
      experimentally, is able to provide a "quasi-ideal" impulse response function and,
      therefore, greatly enhances the depth resolution for characterizing optically
      thin layers in the terahertz regime.

PMID- 28454170
TI  - Origin and suppression of parasitic signals in Kagome lattice hollow core fibers
      used for SRS microscopy and endoscopy.
AB  - Hollow core fibers are considered as promising candidates to deliver intense
      temporally overlapping picosecond pulses in applications such as stimulated Raman
      scattering (SRS) microscopy and endoscopy because of their inherent low
      nonlinearity compared to solid-core silica fibers. Here we demonstrate that,
      contrary to prior assumptions, parasitic signals are generated in Kagome lattice
      hollow core fibers. We identify the origin of the parasitic signals as an
      interplay between the Kerr nonlinearity of air and frequency-dependent fiber
      losses. Importantly, we identify the special cases of experimental parameters
      that are free from parasitic signals, making hollow core fibers ideal candidates
      for noise-free SRS microscopy and endoscopy.

PMID- 28454172
TI  - Are optical fibers really uniform? Measurement of refractive index on a
      centimeter scale.
AB  - Many applications of optical fiber, such as specialized fiber Bragg gratings
      (FBGs), require high uniformity of a fiber's refractive index (RI) along its
      length. We show here that the mode effective index of most fibers is not
      constant, even on a short length scale. To help improve fiber manufacturing and
      selection, we demonstrate a technique for characterizing a meter length single
      mode optical fiber's effective RI over a centimeter scale with a precision of
      3*10<sup>-6</sup> RI units (RIUs) and an absolute accuracy of 2*10<sup>-4</sup>
      RIU. By writing several weak probe FBGs as frequency references and then
      measuring the frequency deviation of these probe FBGs along the length of the
      fiber with an optical frequency domain reflectometer, the RI distribution of the
      effective mode index may be found. We validate our measurements on reference and
      fibers under test with theoretical simulations.

PMID- 28454173
TI  - On the cancellation of OAM beams propagating through convective turbulence.
AB  - By means of an experimental setup, we study the time evolution of orbital angular
      momentum (OAM) crosstalk after a 5 m propagation path with a turbulence
      perturbation generated by a flat heater. This convective turbulence could
      simulate the beam passing over hot concrete or building roofs. We study the
      consequences of using a wide range of transmission OAM states. We also explore
      the effect of misalignment, and we propose two new different techniques for
      analyzing the vortex cancellation. Even though results are inconsistent with
      theoretical predictions, especially for low turbulence regimes, we state that
      signal-to-noise ratio is the key factor to understanding this discrepancy.
      Finally, a crosstalk correction method is proposed via image post-processing that
      would open the possibility of an adaptive optics approach that is different from
      conventional ones.

PMID- 28454174
TI  - Pilot-tone-based self-homodyne detection using optical nonlinear wave mixing.
AB  - An all-optical pilot-tone-based self-homodyne detection scheme using nonlinear
      wave mixing is experimentally demonstrated. Two scenarios are investigated using
      (1) multiple wavelength-division-multiplexed channels with sufficient power of
      the pilot tones and (2) a single channel with a low-power pilot tone. The eye
      diagram and bit error rate of the system are studied by tuning various parameters
      such as pump power, relative phase, and pilot-to-signal ratio.

PMID- 28454175
TI  - Estimation of photonic crystal fiber dispersion by means of supercontinuum
      generation.
AB  - We present a technique for photonic crystal fiber dispersion measurement. We
      demonstrate that investigating supercontinuum using cross-correlation frequency
      resolved optical gating (XFROG) technique can be used for quantitatively
      characterizing dispersion and observing orthogonal polarization modes in
      polarization maintaining photonic crystal fibers. In addition, an XFROG trace of
      supercontinuum generated in a polarization maintaining photonic crystal fiber
      reveals complex behavior of orthogonal polarization modes that is different in
      normal and anomalous dispersion regions of the photonic crystal fiber.

PMID- 28454176
TI  - Phaseless incoherent optical frequency domain spectroscopy.
AB  - We describe a new technique for incoherent optical frequency domain spectroscopy
      (I-OFDS) that does not require measurements of the RF phase spectrum in order to
      reconstruct the optical spectrum. It is based on the addition of either an
      optical or electronic reference line to the I-OFDS system. Compared to the
      spectrum acquired by a regular I-OFDS system, high accuracy (error<1%) is
      predicted and achieved.

PMID- 28454177
TI  - Thulium fiber pumped tunable Ho:CaF<sub>2</sub> laser.
AB  - The paper reports the first room-temperature operation of the in-band pumped
      Ho:CaF<sub>2</sub> laser. A set of Ho:CaF<sub>2</sub> crystals varying in holmium
      concentrations (from 0.1 up to 2.5 mol. % of HoF<sub>2</sub>), synthesized using
      the Bridgeman technique, was used for lasing and related spectroscopy
      investigation. A pulsed 1.94 MUm thulium fiber laser system was used for
      Ho:CaF<sub>2</sub> longitudinal pumping. For 1.5 mol. % of Ho:CaF<sub>2</sub>,
      the maximal wavelength tunability (from 2073 to 2114 nm) and output energy (1.6
      mJ at 2113 nm) were obtained for absorbed pumping energy 34 mJ. Without the
      tuning element, the slope efficiency up to 30% in respect to absorbed power was
      obtained using this sample.

PMID- 28454178
TI  - Optical Nyquist pulse generation by using a dual-electrode Mach-Zehnder
      modulator.
AB  - We demonstrate a simple and efficient optical Nyquist pulse generation by using a
      dual-electrode Mach-Zehnder modulator (MZM) driven by a combination of
      fundamental and second-harmonic RF signals. The method is based on a raised
      cosine-shaped time filter and time lens created in the MZM under operation
      conditions given by a simple equation. Optical Nyquist pulses with a roll-off
      factor of 0.52 and intrinsic conversion efficiency of 37% are experimentally
      confirmed. Numerical analyses indicate that the roll-off factor can be moderately
      controlled down to ~0.3 by increasing relative strength of fundamental RF
      signals.

PMID- 28454179
TI  - Simple effective medium approximation with Rayleigh scattering.
AB  - We present a simple analytical effective medium approximation (EMA) that can
      account for finite-sized and interacting inclusions in the Rayleigh scattering
      regime. The polarizability of an individual inclusion is calculated using the Mie
      solution and net polarizability is formed, leading to effective parameters. The
      Mie coefficients are expanded into polynomials and curtailed to the sixth order,
      which is accurate in the Rayleigh regime. Results obtained using the developed
      models are compared with experimental results and existing EMAs. The analytical
      formula outperforms other EMAs for large inclusion sizes, high filling factors,
      and high relative refractive indices.

PMID- 28454180
TI  - Cryogenically cooled CeF3 crystal as media for high-power magneto-optical
      devices.
AB  - The thermally induced depolarization and Verdet constant of CeF<sub>3</sub>
      crystals-their most important characteristics-have been studied in the 79-293 K
      temperature range. It has been found that thermal effects reduce substantially
      upon cooling down to 79 K and the Verdet constant grows in inverse proportion to
      the temperature. It was shown that CeF<sub>3</sub> crystals are not inferior to
      TGG as a medium for Faraday isolators, including cryogenic ones.

PMID- 28454181
TI  - Demonstration of a highly efficient terahertz flat lens employing tri-layer
      metasurfaces.
AB  - We demonstrate a terahertz flat lens based on tri-layer metasurfaces allowing for
      broadband linear polarization conversion, where the phase can be tuned through a
      full 2pi range by tailoring the geometry of the subwavelength resonators. The
      lens functionality is realized by arranging these resonators to create a
      parabolic spatial phase profile. The fabricated 124-MUm-thick device is
      characterized by scanning the beam profile and cross section, showing diffraction
      limited focusing and ~68% overall efficiency at the operating frequency of 400
      GHz. This device has potential for applications in terahertz imaging and
      communications, as well as beam control in general.

PMID- 28454182
TI  - The Female Pediatric Surgeon.

PMID- 28454183
TI  - Leadership in Pediatric Surgery from a Senior's Perspective.

PMID- 28454184
TI  - [Register of Difficult Surgical Situations].
AB  - Every surgical problem that increases the likelihood of intraoperative and
      postoperative complications is considered to be a difficult surgical situation.
      Based on this definition, Korenkov et al. proposed to classify patients according
      to the following intraoperative difficulty levels (I to IV): (I) ideal situation
      (easy to operate, no problems), (II) fairly easy/manageable/simple (some minor
      difficulties may occur), (III) difficult/problematic (difficult to operate; some
      operative techniques are considerably more difficult than others), and (IV) very
      difficult (every operative step is difficult/challenging). Kaafrani et al.
      proposed a severity classification for intraoperative adverse events. Depending
      on the severity level, classes range from I (injury requiring no repair) to VI
      (intraoperative death). Clavien and colleagues published a globally established
      classification system for postoperative complications. In this classification,
      the severity of postoperative complications ranges from severity grade I (minimal
      deviation from the normal postoperative course) to severity grade V (death of
      patient). Based on the proposed classifications and the problems of individual
      surgical decision-making, we had the idea to create a Register of Difficult
      Intraoperative Situations (DIS register). The basic principle of such a register
      is the collection of an individual expert's experiences. The scientific analysis
      should focus on patients with apparent modifications in treatment due to
      difficult intraoperative situations. Registration and processing of enrolled
      cases will be performed anonymously based on an appropriate IT platform. The main
      goal of this register is to develop an accessible database for practising
      surgeons. This will provide an opportunity for every surgeon to find out what
      other surgeons did in similar situations.

PMID- 28454185
TI  - Patella Dislocation in Children and Adolescents.
AB  - Introduction Patellar dislocation is one of the commonest knee injuries in
      adolescents. Although treatment usually leads to good results, the influence of
      anatomical and functional factors on therapeutic strategy has been
      underestimated, especially in cases of recurrence. Patients and Methods The
      course of treatment has been analysed in 88 patients with 136 patellar
      dislocations. The importance of anatomical conditions was studied using X-ray and
      MRI findings. The treatment results were critically evaluated in comparison with
      current recommendations. Results From 2000 to 2015, 109 patellar dislocations
      occurred in 88 patients; a further 27 previous dislocations were reported by the
      patients (mean age 14 years, 47 boys and 41 girls). About one-third of patients
      (35.2 %) suffered one or more recurrences. Almost half (48.6 %) of the
      dislocations occurred during physical exercise, particularly ball sports.
      Osteochondral flake fracture was found in 9 % of the patients, and a lesion of
      the medial patellofemoral ligament in 96 %. There was an anatomical
      predisposition to patellar dislocation in almost all cases. The sulcus angle,
      patellar and trochlear dysplasia, and patellar height were highly significantly
      different between the patient group and controls. The TT-TG distance was
      subsequently calculated, but had no impact on therapy. Seventy-seven patients
      were treated conservatively and 32 patients surgically. The conservative
      procedure included partial immobilisation for six weeks. Surgical reconstruction
      or tightening was performed in 27 cases; in five, in combination with other
      surgical procedures. Plasty of the medial patellofemoral ligament with a tendon
      graft was performed in five patients, and osteochondral or meniscal lesions were
      repaired in 10 patients. Recurrences occurred in 41.7 % of conservatively treated
      knees and in 29.6 % of surgically treated knees (without reconstruction with a
      tendon graft). No recurrence was seen after reconstruction of the medial
      patellofemoral ligament with a tendon graft. Fifty-four patients underwent a
      follow-up examination. Fourteen of these (25.9 %) had suffered a recurrence. The
      outcome 16 months after the end of treatment was mostly good, as were the results
      of self-assessment (Larson-Lauridsen Score). Conclusion An anatomical
      predisposition is detectable in almost all cases of patellar dislocation, but
      frequently occurs with an accident event, e.g. in ball sports. Primary patellar
      dislocations without serious concomitant injuries may be treated conservatively.
      In the event of recurrence, the indication for surgery is given, even in young
      patients and in any patient with an osteochondral flake fracture. Tightening
      reconstruction of the MPFL used to be frequently performed, but is associated
      with a high rate of recurrence.

PMID- 28454186
TI  - Distribution and Clearance of Blood Constituents after Intracerebral Hemorrhage
      in Rats: Mechanisms and Relevance for Functional Outcomes.
AB  - Background and Objective To evaluate the impact of blood clearance mechanisms on
      neurologic damage and functional outcomes after intracerebral hemorrhage (ICH) in
      rats. Methods A rat model of ICH was established through pre-cannulation and
      injection of autologous arterial blood into the caudate nucleus. Blood was
      supplemented with 6-amino-caproic acid (a procoagulant), low-molecular-weight
      heparin (an anticoagulant), or vehicle. Relationships between hematoma volume and
      edema size and neurologic damage were assessed at different times. Results At 6
      hours and 24 hours, hematoma volume was greater in rats that received
      anticoagulant than in the other two groups (p < 0.01). No significant differences
      were observed at 3 days, 5 days, or 7 days (p > 0.05). At 6 hours and 24 hours,
      the Neurological Severity Score in the procoagulant group was significantly
      higher than in the other two groups (comparison between groups, p < 0.01); and no
      significant differences were found at other times (p > 0.05). Conclusion Enhanced
      clearance of leaked blood was associated with larger hematomas within the first 3
      days of ICH and with less neurologic damage. The capacity to clear blood is an
      important determinant of functional recovery after ICH. Enhanced clearance may
      help reduce neurologic damage.

PMID- 28454187
TI  - Combination of Transforaminal and Interlaminar Percutaneous Endoscopic Lumbar
      Diskectomy for Extensive Down-migrated Disk Herniation.
AB  - BACKGROUND AND STUDY AIMS:  The technique and instrumentation of percutaneous
      endoscopic lumbar diskectomy (PELD) have significantly improved. Thus its
      indications have been gradually expanding. Down-migrated disk, in particular, is
      regarded inaccessible by rigid instrumentation due to poor visualization and
      limited accessibility. We introduce a combination of transforaminal and
      interlaminar PELD for extensive down-migrated disk herniation at the L4-L5 level.
      PATIENTS AND METHODS:  In the first case, a 48-year-old man had left L5 radicular
      pain. Magnetic resonance imaging (MRI) showed that L4-L5 disk herniation extended
      to the L5 lower end-plate level. In the second case, a 39-year-old man presented
      with right L5 and S1 radiculopathy. MRI showed right huge extensive down-migrated
      disk herniation from the L4-L5 disk space to the S1 pedicle level. Back pain and
      leg pain were measured using the visual analog scale (VAS). In the first case,
      transforaminal PELD with foraminoplasty removed the disk fragment from the L4-L5
      disk space to the mid-L5 pedicle level. Interlaminar PELD removed the remaining
      disk below the mid-L5 pedicle. In the second case, first, contralateral (left)
      transforaminal PELD at L4-L5 removed disk fragments located at the subannular and
      subligamentous area as well as the upper part of the down-migrated disk
      herniation. Second, interlaminar PELD via an ipsilateral (right) L5-S1
      interlaminar space removed the remains of the extensively down-migrated disk
      herniation. RESULTS:  In the first case, the VAS scores for back and leg pain
      were improved from 6 and 8 to 2 and 1, respectively. Postoperative MRI showed
      complete removal of the disk fragment. In the second case, the VAS scores for
      back and leg pain improved from 7 and 9 to 3 and 1, respectively, after PELD.
      Postoperative MRI showed complete removal of a huge disk herniation. Both
      patients were discharged the day after PELD. Follow-up examinations showed no
      recurrence. CONCLUSIONS:  It is difficult to remove entire disk fragments using
      only a transforaminal or interlaminar approach for extensive down-migrated disk
      herniation. Therefore a combination of transforaminal and interlaminar PELD may
      be effective for extensive down-migrated disk herniation at L4-L5.

PMID- 28454188
TI  - Metabolic Profiling of Hoodia, Chamomile, Terminalia Species and Evaluation of
      Commercial Preparations Using Ultrahigh-Performance Liquid Chromatography
      Quadrupole-Time-of-Flight Mass Spectrometry.
AB  - Ultrahigh-performance liquid chromatography quadrupole-time-of-flight mass
      spectrometry (UHPLC-QToF-MS) profiling was used for the identification of marker
      compounds and generation of metabolic patterns that could be interrogated using
      chemometric modeling software. UHPLC-QToF-MS was used to generate comprehensive
      fingerprints of three botanicals (Hoodia, Terminalia, and chamomile), each having
      different classes of compounds. Detection of a broad range of ions was carried
      out in full scan mode in both positive and negative modes over the range m/z 100
      1700 using high-resolution mass spectrometry. Multivariate statistical analysis
      was used to extract relevant chemical information from the data to easily
      differentiate between Terminalia species, chamomile varieties, and quality
      control of Hoodia products. Using nontargeted analysis, identification of 37
      compounds contributed to the differences between Terminalia species, 26
      flavonoids were identified to show the differences between German and Roman
      chamomile, and 43 pregnane glycosides were identified from Hoodia gordonii
      samples. The UHPLC-QToF-MS-based chemical fingerprinting with principal component
      analysis was able to correctly distinguish botanicals and their commercial
      products. This work can be used as a basis to assure the quality of botanicals
      and commercial products.

PMID- 28454189
TI  - Assessment of the Authenticity of Herbal Dietary Supplements: Comparison of
      Chemical and DNA Barcoding Methods.
AB  - About 7 % of the U. S. population reports using botanical dietary supplements.
      Increased use of such supplements has led to discussions related to their
      authenticity and quality. Reports of adulteration with substandard materials or
      pharmaceuticals are of concern because such substitutions, whether inadvertent or
      deliberate, may reduce the efficacy of specific botanicals or lead to adverse
      events. Methods for verifying the identity of botanicals include macroscopic and
      microscopic examinations, chemical analysis, and DNA-based methods including DNA
      barcoding. Macroscopic and microscopic examinations may fail when a supplement
      consists of botanicals that have been processed beyond the ability to provide
      morphological characterizations. Chemical analysis of specific marker compounds
      encounters problems when these compounds are not distinct to a given species or
      when purified reference standards are not available. Recent investigations
      describing DNA barcoding analysis of botanical dietary supplements have raised
      concerns about the authenticity of the supplements themselves as well as the
      appropriateness of using DNA barcoding techniques with finished botanical
      products. We collected 112 market samples of frequently consumed botanical
      dietary supplements of ginkgo, soy, valerian, yohimbe, and St. John's wort and
      analyzed each for specific chemical markers (i.e., flavonol glycosides, total
      isoflavones, total valerenic acids, yohimbine, and hypericins, respectively). We
      used traditional DNA barcoding techniques targeting the nuclear ITS2 gene and the
      chloroplast gene psbA-trnH on the same samples to determine the presence of DNA
      of the labelled ingredient. We compared the results obtained by both methods to
      assess the contribution of each in determining the identity of the samples.

PMID- 28454190
TI  - Evaluation of the Effect of Epilobium angustifolium Aqueous Extract on LNCaP Cell
      Proliferation in In Vitro and In Vivo Models.
AB  - Epilobium sp. are commonly used in traditional medicine in the treatment of early
      stages of benign prostatic hyperplasia and inflammation. It is suggested that a
      dominating constituent, oenothein B, is responsible for the extracts therapeutic
      effects. Several bioactivities were established for extracts and oenothein B in
      various in vitro models, but due to the questionable bioavailability of this
      dimeric macrocyclic ellagitannin, their significance in the in vivo effects
      remains unresolved. We have thus focused our attention on a complex comparative
      investigation of the in vitro and in vivo activities of phytochemically
      characterized Epilobium angustifolium aqueous extract and oenothein B on prostate
      cancer cells proliferation.Incubation of different cell lines with E.
      angustifolium aqueous extract resulted in a significant reduction of
      proliferation of PZ-HPV-7 and LNCaP cells, which was partly associated with
      antiandrogenic activity. These effects were fully congruent with oenothein B,
      examined in parallel. Oral supplementation of rats implanted with LNCaP cells
      with E. angustifolium aqueous extract 50-200 mg/kg b. w. resulted in a reduction
      of the occurrence of prostatic adenoma up to 13 %. Oenothein B was not detected
      in the urine and feces of the E. angustifolium aqueous extract-treated group,
      however, conjugates of nasutins gut microbiota metabolites of ellagitannins were
      detected in the urine, while in human volunteers supplemented with Epilobium tea,
      only urolithin conjugates were present.Despite observing significant and
      consistent effects in vitro and in vivo, we were unable to point out
      unequivocally the factors contributing to the observed E. angustifolium aqueous
      extract activity, facing the problems of an unknown metabolic fate of oenothein B
      and interspecies differences in E. angustifolium aqueous extract gut microbiota
      metabolism.

PMID- 28454191
TI  - [Distress, Main Burdens, Engagement Motivators and Needs of Fulltime and
      Volunteer Refugee Aid Workers].
AB  - In the psychosomatic department of the University Hospital of Erlangen trainings
      were conducted for active refugee aid workers with start in January, 2016.
      Meanwhile 49 helpers participated in the training and 45 of them filled out a
      survey questionnaire. Perceived distress when providing care for refugees, as
      well as engagement motivation and further training needs were explored.
      Furthermore, depressive symptoms as well as the prevalence of traumatic
      experiences were investigated. The main burden was experienced through lacking
      freedom of action on the background of legal regulations. Furthermore
      dissociative symptoms (15.4%) and aggressive behavior (26.9%) of refugees were
      reported as distress factors. To help others proved to be the highest motivator
      for their work with refugees. Only 2 workers (4.4%) showed elevated depressive
      symptom manifestations. In contrast, 93.3% of refugee helpers had experienced a
      traumatic event personally or as a witness. For the helpers the greatest training
      needs were the recognition of mental health problems and to learn concrete
      intervention strategies to help those affected.

PMID- 28454192
TI  - [Religious/Spiritual Needs and Psychosocial Burden of Melanoma Patients].
AB  - Questions of meaning and purpose in life are becoming relevant during cancer.
      Studies have shown that most patients have spiritual needs and that
      religion/spirituality can be an important ressource in coping with illness. So
      far, only few studies examine the psychosocial burden and the role of spiritual
      needs during the treatment process of patients with malignant melanoma. 22
      patients were included in this study and assessed for psychosocial distress and
      spiritual needs while being screened for cancer metastases (t1) and 8 weeks later
      (t2). Distress, anxiety and depression, furthermore spiritual needs and
      religiousness were examined with standardized assessments (HSI, DT, HADS, PHQ-2,
      SpNQ, SpREUK). All patients express spiritual needs independent of the time of
      measurement and overall burden. Important needs are the need to be complete and
      safe, the need for social support, for actively giving and for inner peace and
      the possibility to talk about anxiety and sorrow. Analyses have shown that
      religious patients are less distressed 8 weeks later, while there was no
      difference in the first time of measurement. The results show the importance to
      include spiritual needs in the process of treatment of cancer in a clinical and
      ambulatory context. Results indicate that religion/spirituality could be an
      important resource to cope with cancer. During the process of treatment,
      spiritual needs could be addressed by psychooncology and pastoral care with
      respect for their different approach and address this topic to support cancer
      patients.

PMID- 28454193
TI  - [Mental Stress of Professionals in Residential Care for Children and
      Adolescents].
AB  - An increasingly important issue is the mental strain of professionals in
      residential care for children and adolescents. However, only few studies
      investigate mental strain and overload of professionals in an educational context
      in general and even less in youth welfare institutions. The goal of this study
      was to examine mental strain experiences of professionals with the "Perceived
      Stress Questionnaire" (PSQ) in youth welfare institutions, as well as to
      investigate the relationship between age, duration of employment in this work
      environment and gender of participants. A total of 426 care providers
      participated in the online survey. The results tend to show higher stress levels
      among younger professionals and significantly higher values in tension compared
      to older employees, but no effect of gender. Furthermore, there is no relation
      between stress experience and duration of employment in this work environment,
      but a significant correlation between a feeling of security from violence in this
      institution and stress level. The total score for stress experience of
      professionals is similar to that of healthy adults, while in the subscales
      compared to the norm sample professionals show higher scores on requirements in
      terms of deadlines and time pressure as well as on tension. The results indicate
      a high vulnerability of young professionals, which could be addressed by
      institutional interventions. More studies are needed to clarify causal
      relationships.

PMID- 28454194
TI  - [Influence of Operative and Conservative Therapy on the Ability to Work of
      Patients With Subacromial Impingement: A Prospective Clinical Comparative Study].
AB  - Background Subacromial impingement is a common reason for pain in the shoulder.
      Treatment is difficult and patients are not able to work for a long time. An
      increasing number of operative treatments can be observed although conservative
      treatment is effective, too. There is no study that observed how operative and
      conservative treatment influence ability to work. Methods 86 persons were
      included in this prospective study. Surgery was performed with an arthroscopy of
      the shoulder. Conservative treatment was carried out by a physiotherapist under
      control of the physician. Reevaluation was conducted 3 and 6 months after the
      initial contact. Here we observed the time the participant was not able to work,
      Constant Score and pain on the numeric rating scale. Results Both therapies were
      able to improve pain and function. During conservative treatment, improvement was
      faster than under operative care. Time without ability to work was 7 +/- 5 weeks
      longer after operative treatment than under conservative therapy (p < 0.001). No
      relevant influence of acromioclavicular joint arthrosis could be observed.
      Bursitis subacromialis detected in the MRI was a predictor of faster recovery.
      Conclusion Conservative and operative treatment improved pain and function
      significantly. Properly carried out conservative therapy enables patients to get
      back to work earlier.

PMID- 28454195
TI  - [Unicompartmental vs. Total Knee Arthroplasty for Medial Osteoarthritis].
AB  - Background In end-stage medial osteoarthritis, the surgeon can decide whether to
      use unicompartmental or total knee arthroplasty for operative treatment of the
      patient. Despite the available literature there is a lack of evidence to suggest
      if one procedure can be rated as being superior to the other. With increasing
      demand for knee arthroplasty, treatment with the highest expectation of success
      will be of particular interest. The purpose of this manuscript was to analyse and
      compare the available literature on unicompartmental vs. total knee arthroplasty
      for the treatment of medial osteoarthritis. Material and Methods In this review
      of literature, the two procedures were compared regarding their clinical outcome,
      implant survival, and complication rates. Results Regarding the clinical outcome
      the unicompartmental knee arthroplasty was shown to be superior over total knee
      arthroplasty. However, studies were mostly retrospective and groups were also
      different preoperatively. Patients treated with unicompartmental knee
      arthroplasty had better preoperative range of motion and function scores.
      Unicompartmental and total knee arthroplasty showed comparably increased
      functional scores. Taking the implant survival as parameter, institutional
      registries, multicenter studies and arthroplasty registries found total knee
      arthroplasties to have a significantly better long-term survival in comparison to
      unicompartmental knee arthroplasty. However, data might be biased by the lower
      threshold to revise unicompartmental knee arthroplasty due to expected simple
      revision and more subjective indications for revision. Looking at the
      complication rate, one has to differentiate between general and implant-specific
      complications. While the unicompartmental knee arthroplasty was shown to be
      advantageous in terms of general complications and mortality, it was also shown
      to be inferior in terms of implant-specific complications. Conclusion The
      available literature does not show one procedure to be superior to the other. The
      trend to a better clinical outcome and a lower mortality rate is advantageous for
      unicompartmental knee arthroplasty, while the better long-term survival and a
      lower risk of implant-specific complications may make total knee arthroplasty
      preferable.

PMID- 28454196
TI  - [Diagnostic Procedures in Hereditary Diseases].

PMID- 28454197
TI  - [80-year-old Patient without Recognizable Heart on Transesophageal
      Echocardiografy].

PMID- 28454198
TI  - [No Magic Bullet: Genetic Diagnostics and Predictive Testing].
AB  - The enormous increase in knowledge about the genetic basis of human diseases,
      combined with the rapid development of genetic techniques, has led to the
      possible use of genetic tests in medical diagnostics to a degree previously
      unknown. In addition, predictive genetic diagnostics has the aim of identifying
      hereditary disease risks in healthy individuals in order to take precautionary
      measures. However, the assessment of genetic findings is still subject to
      numerous problems. In particular, in the case of disease prediction, only
      probability statements can be made since endogenous and exogenous factors
      influence the penetrance and expressivity of genetically determined diseases.

PMID- 28454199
TI  - [Genetic diagnostics for cardiomyopathies].
AB  - Cardiomyopathies often have a genetic etiology. New genetic diagnostic strategies
      based on next generation sequencing (NGS)-approaches will continuously increase
      our knowledge about the genetic basis of cardiomyopathies within the following
      years. Diagnostics and therapy of rare, genetically-induced cardiac diseases
      increasingly require special cardiac and genetic knowledge. Interestingly,
      mutations in the same gene or even identical gene mutations can be associated
      with different cardiomyopathy phenotypes and can exhibit incomplete penetrance or
      variable expressivity. In the future, the correct interpretation and
      classification of novel gene variants identified in patients with inherited
      cardiomyopathy forms will represent a great challenge. Genetic counselling and -
      if appropriate - subsequent genetic testing for cardiomyopathy patients and their
      asymptomatic relatives is essential for an early diagnosis of the disease, a
      prognostic evaluation and possibly for the start of preventive or therapeutic
      measures.

PMID- 28454200
TI  - [Genetic Causes of Endocrine Diseases Using the Example of Endocrine Tumor
      Syndromes].

PMID- 28454201
TI  - [Identical Variants Different Disease Course - Genetics of Chronic Pancreatitis].
AB  - Multiple genetic associations with chronic pancreatitis have been identified. In
      cases with hereditary pancreatitis family history is reported and mostly distinct
      causative variants in cationic trypsinogen (PRSS1) are identified. Furthermore,
      variants in other genes of proteases and anti-proteases of the digestive enzyme
      cascade (SPINK1, CTRC, CPA1), are also associated with chronic pancreatitis.
      Interestingly, penetrance of associated variants as well as the disease course
      are variable. As such environmental factors like smoking may play an important
      role. Patients with chronic pancreatitis of unknown etiology should be offered
      genetic testing after referral to a pancreatic center.

PMID- 28454202
TI  - [New Developments in Compression Treatment].
AB  - Patients with peripheral arterial occlusive disease who show an ankle arterial
      pressure of minimum 60 mmHg can be decongested by use of special padded bandages.
      Afterwards, medical compression stockings (class 1) with high strength and less
      elasticity are recommended. Mobile patients seem to benefit from progressive
      compression therapy with highest pressure above the calf. Compression after
      uncomplicated interventions of varicose veins or spider veins tends to be
      modified to a short and excentric compression in patients without risk factors.
      Valid datas are not available yet. Adaptive compression bandages show pros
      concerning efficiency, economy and more comfort for patients with edemas or
      ulcers.

PMID- 28454203
TI  - [Genetic Diagnosis in Familial Hypercholesterolemia - yes].

PMID- 28454204
TI  - [Genetic Diagnosis in Familial Hypercholesterolaemia - no].

PMID- 28454205
TI  - [Re: Disorders of the Acid-Base Balance and the Anion Gap].

PMID- 28454206
TI  - [In reply].

PMID- 28454207
TI  - ?

PMID- 28454208
TI  - ?

PMID- 28454209
TI  - Reply.

PMID- 28454210
TI  - Statins and pancreatic cancer.
AB  - Pancreatic cancer remains among the most lethal cancers, despite ongoing advances
      in treatment for all stages of the disease. Disease prevention represents another
      opportunity to improve patient outcome, with metabolic syndrome and its
      components, such as diabetes, obesity and dyslipidemia, having been recognized as
      modifiable risk factors for pancreatic cancer. In addition, statins have been
      shown to potentially reduce pancreatic cancer risk and to improve survival in
      patients with a combination of metabolic syndrome and pancreatic cancer.
      Furthermore, preclinical studies have demonstrated that statins exhibit antitumor
      effects in pancreatic cancer cell lines in vitro and animal models in vivo, in
      addition to delaying the progression of pancreatic intraepithelial neoplasia to
      pancreatic ductal adenocarcinoma (PDAC) and inhibiting PDAC formation in
      conditional K-Ras mutant mice. The mechanisms by which statins produce anticancer
      effects remain poorly understood, although appear to involve inhibition of the
      mevalonate/cholesterol synthesis pathway, thus blocking the synthesis of
      intermediates important for prenylation and activation of the Ras/mitogen
      activated protein kinase 1 signaling pathway. Furthermore, statins have been
      identified to modulate the phosphoinositide 3-kinase/Akt serine/threonine kinase
      1 and inflammation signaling pathways, and to alter the expression of genes
      involved in lipid metabolism, which are important for PDAC growth and
      proliferation. In addition, statins have been demonstrated to exhibit further
      antitumor mechanisms in a number of other cancer types, which are beyond the
      scope of the present review. In the present review, current evidence highlighting
      the potential of statins as chemopreventive agents in pancreatic cancer is
      presented, and the antitumor mechanisms of statins elucidated thus far in this
      disease are discussed.

PMID- 28454211
TI  - Targeting the Ras/Raf/MEK/ERK pathway in hepatocellular carcinoma.
AB  - Although the biological basis of hepatocellular carcinoma (HCC) remains unclear,
      effective treatments and improvement of the survival rate remain worthwhile
      research goals. Abnormal protein signaling pathways contributing to uncontrolled
      cell proliferation, differentiation, survival and apoptosis are biomarkers of the
      carcinogenic process. Certain mutated components or overexpression of the rat
      sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated
      protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling
      pathway are increasingly being studied in HCC carcinogenesis. The present review
      addresses the effect of the Ras/Raf/MEK/ERK signaling pathway on the pathogenesis
      of HCC, and provides an update on the preclinical and clinical development of
      various inhibitors targeting this core signaling pathway, which include various
      Ras inhibitors, Raf inhibitors and MEK inhibitors for HCC.

PMID- 28454212
TI  - Reciprocal regulation between microRNAs and epigenetic machinery in colorectal
      cancer.
AB  - Epigenetics encompasses changes in DNA methylation, histone and chromatin
      structure, and non-coding RNAs, specifically microRNA (miRNA) expression. Recent
      advances in the rapidly evolving field of colorectal cancer (CRC) epigenetics
      have revealed a complicated network of reciprocal interconnections between miRNAs
      and other epigenetic machinery. On the one hand, miRNA expression may be
      regulated by epigenetic mechanisms including DNA methylation and histone
      modifications. However, miRNAs may affect the epigenetic machinery by directly
      targeting its enzymatic components. In this study, we focus on the colorectal
      miRNA expression profile and further illustrate the reciprocal regulation in CRC,
      with the aim of offering new insights into the strategies of combatting the
      disease.

PMID- 28454213
TI  - Proteasome inhibitors in glioblastoma.
AB  - Glioblastomas (GBM) are the tumors originating from the star shaped supportive
      cells in brain known as astrocytes. These tumors are highly cancerous as they
      have the ability to proliferate very quickly. New therapeutic strategies are
      being developed worldwide to fight against deadly GBM, which has median survival
      time of just 14 months. Proteasome inhibition is an upcoming strategy for GBM.
      Proteasome inhibition has shown promising results in cancers such as myeloma.
      However, in the recent past this form of therapy has also shown positive results
      in brain tumors in the form of elevated apoptosis. We searched the electronic
      database PubMed for pre-clinical as well as clinical controlled trials reporting
      importance of proteasome inhibitors during GBM. It was observed clearly that this
      approach is evolving and has been observed to be promising therapeutic avenue
      against GBM. Thus, the present review aims to enlighten the present views on use
      of proteasome inhibition strategy in the case of GBM.

PMID- 28454215
TI  - Evaluation of ALDH1 expression in ipsilateral breast cancer recurrence.
AB  - Aldehyde dehydrogenase 1 (ALDH1) is a cancer stem cell (CSC) marker that is
      easily evaluable. The expression and clinical significance of ALDH1 in
      ipsilateral breast tumor recurrence (IBTR) has yet to be investigated. In the
      present study, the expression profile of ALDH1 and its correlation with prognosis
      in IBTR tissues was examined. Patients with IBTR from eight institutions were
      retrospectively enrolled in the study. Immunohistochemistry was used to examine
      ALDH1 expression patterns in the tissue specimens of primary cancers and IBTRs.
      ALDH1 expression levels were investigated in 182 IBTR tumors, which included
      cases of invasive carcinoma selected from 271 consecutive patients with IBTR.
      ALDH1 was expressed in 23% of the IBTR tissue samples. The rate of concordant
      expression between primary cancer and IBTR tissues was 68%. There was no
      significant association between disease-free survival (DFS) and ALDH1 expression
      levels in IBTR. IBTRs that expressed ALDH1 and Ki-67 had a poorer prognosis and
      this expression pattern was significantly associated with DFS (P=0.0073). The
      percentages of ALDH1 positive expression in each tissue subtype were as follows:
      Luminal A, 20%; luminal B, 24%; human epidermal growth factor 2 (HER2), 35%;
      triple-negative, 21%. There was a significant correlation between DFS and ALDH1
      expression levels in HER2-type IBTR tissue specimens (P=0.034). In conclusion, it
      is possible that ALDH1 and Ki-67 expression levels may be useful for predicting
      prognosis in patients with HER2-type tumors.

PMID- 28454214
TI  - Genome-wide analysis of gynecologic cancer: The Cancer Genome Atlas in ovarian
      and endometrial cancer.
AB  - Cancer typically develops due to genetic abnormalities, but a single gene
      abnormality cannot completely account for the onset of cancer. The Cancer Genome
      Atlas (CGA) project was conducted for the cross-sectional genome-wide analysis of
      numerous genetic abnormalities in various types of cancer. This approach has
      facilitated the identification of novel AT-rich interaction domain 1A gene
      mutations in ovarian clear cell carcinoma, frequent tumor protein 53 (TP53) gene
      mutations in high-grade ovarian serous carcinoma, and Kirsten rat sarcoma and B
      rapidly accelerated fibrosarcoma proto-oncogene, serine/threonine kinase gene
      mutations in low-grade ovarian serous carcinoma. Genome-wide analysis of
      endometrial cancers has led to the establishment of four subgroups: Polymerase
      ultramutated, microsatellite instability hypermutated, genome copy-number low and
      genome copy-number high. These results may facilitate the improvement of the
      prediction of patient prognosis and therapeutic sensitivity in various types of
      gynecologic cancer. The enhanced use of currently available therapeutic agents
      and the development of novel drugs may be facilitated by the novel classification
      of ovarian cancer based on TP53 mutations, the efficacy of poly (ADP-ribose)
      polymerase inhibitors for tumors with breast cancer 1/2 mutations and the effect
      of phosphoinositide-3-kinase (PI3K)/mammalian target of rapamycin inhibitors for
      tumors with mutations in the PI3K/protein kinase B signaling pathway. Important
      results have been revealed by genome-wide analyses; however, the pathogenic
      underlying mechanisms of gynecologic cancer will require further studies and
      multilateral evaluation using epigenetic, transcriptomic and proteomic analyses,
      in addition to genomic analysis.

PMID- 28454216
TI  - MicroRNA-31 functions as an oncogenic microRNA in cutaneous squamous cell
      carcinoma cells by targeting RhoTBT1.
AB  - Cutaneous squamous cell carcinoma (cSCC) is a malignancy of epidermal
      keratinocytes that is responsible for ~20% of annual skin cancer-associated
      mortalities. Accumulating evidence demonstrates that the dysregulation of micro
      (mi)RNAs serves a significant role in the tumorigenesis and progression of human
      cSCC. MicroRNA-31 (miR-31) is upregulated in cSCC and is involved in cSCC
      development. However, the underlying mechanism remains unclear. The present study
      demonstrated that miR-31 is upregulated in the cSCC cell line, A-431, and that
      miR-31 expression contributes to the cell proliferation and invasion of cSCC. In
      addition, bioinformatics combined with dual luciferase reporter analysis was
      applied to determine that the tumor suppressor RhoTBT1 was a direct target of miR
      31. In addition, miR-31 mimics reduced RhoBTB1 expression in A-431 cells. The
      results of MTT and Transwell assays demonstrated that knockdown of RhoBTB1 by
      short interfering RNA induced cell proliferation and invasion in A-431 cells.
      These results indicated that suppression of RhoBTB1 may be involved in cSCC
      tumorigenesis, which was directly affected by miR-31. In conclusion, the present
      study provides evidence that miR-31 acts as an oncogene through direct repression
      of RhoTBT1 expression in cSCC cancer, suggesting a potential application of miR
      31 in prognosis prediction and its therapeutic application in cSCC.

PMID- 28454217
TI  - Paraganglioma of the organ of Zuckerkandl associated with a somatic HIF2alpha
      mutation: A case report.
AB  - Paragangliomas of the organ of Zuckerkandl (OZ-PGL) are rare tumors that, in >70%
      of cases, occur in association with succinate dehydrogenase complex iron sulfur
      subunit B (SDHB) or SDHD gene mutations. The aim of the current study was to
      determine whether a somatic genetic defect in the hypoxia-inducible factor 2alpha
      (HIF2alpha) gene was present in a case of sporadic OZ-PGL. A 32-year-old African
      female presented with uncontrolled hypertension during the first trimester of
      pregnancy. A diagnostic hysteroscopy was performed 3 months after delivery,
      precipitating a hypertensive crisis. Thereafter, the patient was diagnosed with
      noradrenaline-secreting OZ-PGL. A complete blood count identified mild normocytic
      anemia of an inflammatory origin. Surgical removal of the tumor resulted in
      normalization of plasma and urinary normetanephrine levels. Genetic testing for
      germline mutations (including large deletions) in the von Hippel-Lindau tumor
      suppressor, SDHB, SDHC and SDHD genes was normal. However, a heterozygous
      missense mutation (c.1589Cys>Tyr) was detected in exon 12 of HIF2alpha, which
      results in a substitution of alanine 530 with valine (Ala530Val) in the HIF2alpha
      protein. A germline mutation was excluded based on the negative results of blood
      DNA testing. A three-dimensional homology model of Ala530Val was constructed,
      which showed impaired HIF2alpha/VHL interaction and decreased HIF2alpha
      ubiquitination. 1H-high-resolution magic-angle-spinning nuclear magnetic
      resonance spectroscopy detected low succinate levels and high alpha and beta
      glucose levels. To the best of our knowledge, the present case represents the
      first of its kind to associate a somatic HIF2alpha gain-of-function mutation with
      OZ-PGL. It is therefore recommended that patients without germline SDHx mutations
      should be tested for HIF2alpha mutations.

PMID- 28454218
TI  - Stereotactic body radiation therapy for oligoprogression of metastatic disease
      from gastrointestinal cancers: A novel approach to extend chemotherapy efficacy.
AB  - Chemotherapy and targeted therapies are effective palliative options for numerous
      unresectable or metastatic cancers. However, treatment resistance inevitably
      develops leading to mortality. In a subset of patients, systemic therapy appears
      to control the majority of tumors leaving 5 or less to progress, a phenomenon
      described as oligoprogression. Reasoning that the majority of lesions remain
      responsive to ongoing systemic chemotherapy, we hypothesized that local treatment
      of the progressing lesions would confer a benefit. The present study describes
      the cases of 5 patients whose metastatic disease was largely controlled by
      chemotherapy. The oligoprogressive lesions (<=5) were treated with stereotactic
      body radiotherapy (SBRT), justifying continued use of an effective systemic
      regimen. A total of 5 patients with metastatic disease on chemotherapy, with <=5
      progressing lesions amenable to SBRT, were treated with ablative intent. Primary
      tumor site and histology were as follows: 2 with metastatic colon adenocarcinoma,
      2 with metastatic rectal adenocarcinoma and 1 with metastatic pancreatic
      adenocarcinoma. Imaging was performed prior to SBRT and every 3 months after
      SBRT. In total, 4 out of the 5 patients achieved disease control for >7 months
      with SBRT, without changing chemotherapy regimen. The median time to chemotherapy
      change was 9 months, with a median follow-up time of 9 months. The patient who
      failed to respond developed progressive disease outside of the SBRT field at 3
      months. In conclusion, the addition of SBRT to chemotherapy is an option for the
      overall systemic control of oligoprogressive disease.

PMID- 28454219
TI  - Extracellular HSP70/HSP70-PCs regulate hepatocarcinoma cell migration and
      invasion via RhoA.
AB  - The effects of heat shock protein 70 (HSP70)/HSP70-peptide complexes (HSP70-PCs)
      on the invasion and metastasis ability of hepatocellular carcinoma (HCC) Huh-7
      cells were investigated. Wound healing assay revealed that cells treated with
      HSP70/HSP70-PCs healed faster than negative control cells. HSP70/HSP70-PCs
      treated cells also exhibited better migration ability and higher invasion ability
      than control cells. HSP70/HSP70-PCs treatment did not alter the messenger RNA
      (mRNA) or protein levels of matrix metalloproteinase-9; the opposite was true for
      Ras homolog family member A (RhoA) mRNA and protein levels. RNA interference of
      RhoA attenuated the migration of HSP70/HSP70-PCs-treated cells. The present
      findings indicate that regulation of HCC cell migration by HSP70/HSP70-PCs occurs
      via regulation of RhoA expression.

PMID- 28454220
TI  - Efficacy of pEgr-1-endostatin combined with ionizing radiation on hypoxic
      conditions in nude mice bearing SKOV3 ovarian carcinoma.
AB  - Hypoxia occurs in a wide range of solid tumors, and is strongly associated with
      radio-resistance of malignant tumors. The aim of the present study was to
      investigate the effect of endostatin combined with ionizing radiation (IR) on
      hypoxic conditions. A total of 24 mice bearing SKOV3 ovarian carcinoma were
      divided into three groups. Following injection with pEgr-1-endostatin plasmid for
      12 h, the mice in the endostatin-IR-treated group were exposed to 300 cGy/min X
      ray for 48 h, and the IR-treated group was exposed to the same condition. Then,
      the expression of endostatin, hypoxia-inducible factor (HIF)-1alpha and vascular
      endothelial growth factor (VEGF) was detected by reverse transcription-polymerase
      chain reaction, ELISA, immunohistochemistry and western blotting. In addition,
      the tumor microvessel density (MVD) was examined by immunohistochemistry analysis
      of cluster of differentiation 31-positive cells. The results revealed that pEgr-1
      endostatin was successfully induced by IR. The level of endostatin messenger RNA
      in the endostatin-IR-treated group was significantly higher than that in the
      control and IR-treated groups (F=380.078, P<0.001). Statistical differences were
      also examined at the protein level by western blotting and ELISA. An obvious
      increase in MVD was observed in the IR-treated group compared with that in the
      control group (t=7.040, P<0.001), and a significant decrease in MVD was observed
      in the endostatin-IR-treated group compared with that in the control group
      (t=18.153, P<0.001). By comparing the morphology of the tumor vasculature in the
      three groups, it was noticed that the microvessels in the endostatin-IR-treated
      group were more regularly distributed and had fewer giant branches than those in
      the IR-treated group. Further investigation revealed that the expression levels
      of HIF-1alpha and VEGF in the endostatin-IR-treated group were lower compared
      with those in the control (t=5.339, P=0.001; and t=13.880, P<0.001, respectively)
      and the IR-treated groups (t=12.930, P<0.001; and t=14.050, P<0.001,
      respectively). Our findings suggested that endostatin decreased the number of
      microvessels via the HIF-1/VEGF signaling pathway, and that pEgr-1-endostatin
      combined with IR may improve hypoxic conditions and may be a novel approach for
      treating solid tumors.

PMID- 28454221
TI  - Expression of inositol-requiring enzyme 1beta is downregulated in colorectal
      cancer.
AB  - The endoplasmic reticulum stress inositol-requiring enzyme (IRE) 1alpha/X-box
      binding protein (XBP) 1 signaling pathway is involved in the tumorigenesis of
      breast and prostate cancer. Mucin 2 (MUC2) protects colon tissues from the
      formation of tumors. In human colorectal cancer (CRC) the role of IRE1alpha, and
      its analogue, IRE1beta, has yet to be elucidated. In the present study, the
      expression levels of IRE1alpha, IRE1beta, un-spliced XBP1u, spliced XBP1s and
      MUC2 in surgically resected cancerous and adjacent non-cancerous tissues from
      patients with CRC were investigated. The IRE1alpha, IRE1beta, XBP1u, XBP1s and
      MUC2 mRNA expression levels were determined using reverse transcription
      quantitative polymerase chain reaction, and the protein expression levels were
      detected using immunohistochemistry and western blotting. The association between
      the expression levels of IRE1alpha, IRE1beta and MUC2 and the clinicopathological
      features of patients with CRC was subsequently analyzed. The mRNA expression
      levels of IRE1beta and MUC2 were decreased by ~2.1 and ~4.5-fold in CRC tissues,
      respectively, as compared with the adjacent normal tissues. The protein
      expression levels of IRE1beta and MUC2 were decreased by ~8.0 and ~2.0-fold in
      the CRC tissues, respectively. IRE1beta mRNA expression levels were positively
      correlated with MUC2 mRNA expression levels. IRE1beta expression levels were
      revealed to be significantly associated with lymph node metastasis, tumor stage
      and histological differentiation. However, IRE1alpha, XBP1u and XBP1s mRNA and
      IRE1alpha protein expression levels were not observed to significantly differ
      between cancerous tissues and the adjacent normal tissues. The results indicated
      that the expression of IRE1beta, but not IRE1alpha, may protect colon tissue from
      developing CRC by inducing MUC2 expression. Therefore, decreased IRE1beta
      expression levels may be associated with the development of CRC through the
      inhibition of MUC2 expression.

PMID- 28454222
TI  - Effects of RNA silencing of matrix metalloproteinase-2 on the growth of
      esophageal carcinoma cells in vivo.
AB  - Esophageal carcinoma is one of the most common malignancies in China. Previous
      studies reported that matrix metalloproteinases (MMPs) have important roles in
      the progression and invasion of numerous types of solid tumors. Among the MMPs,
      MMP-2 has been closely associated with tumor growth and invasion. In the present
      study, a short hairpin RNA (shRNA) lentiviral expression vector targeting the MMP
      2 gene was constructed in order to observe the inhibitory effect of MMP-2 gene
      silencing on the growth of the KYSE150 esophageal carcinoma cell line in vivo.
      Three small hairpin RNA sequences targeting MMP-2 were designed and cloned into
      lentiviral vectors. Following transfection of the lentiviral vectors into KTSE150
      cells, MMP-2 mRNA and protein expression levels were examined by reverse
      transcription-quantitative polymerase chain reaction and western blotting, and
      the growth rate of cells was analyzed by MTT assays. Subsequently, tumor growth
      was assessed in nude mice. Lentivirus-mediated RNA interference effectively
      inhibited the expression of MMP-2 mRNA and protein in KYSE150 esophageal
      carcinoma cells, and suppressed the growth of esophageal carcinoma cells in vivo.
      The results of the present study suggested that lentivirus-mediated gene therapy
      targeting MMP-2 may be an attractive strategy for the treatment of esophageal
      carcinoma and justifies the performance of further studies on the application of
      lentivirus vectors to cancer gene therapy.

PMID- 28454223
TI  - Surgical treatment of solid hemangioblastomas of the posterior fossa: A report of
      28 cases.
AB  - This study evaluated the clinical features, treatment strategies and outcomes of
      solid hemangioblastomas in 28 patients diagnosed with hypervascular lesions in
      the posterior fossa. Preoperative embolization of the feeding arteries had
      limited effects, with only 7 patients benefitting from it for the reduction of
      intraoperative hemorrhage. The tumor was completely removed in all patients, and
      22 patients had a full recovery, while 6 patients, all of whom had van Hippel
      Lindau disease, developed recurrences. The present study demonstrated that
      meticulous en bloc surgical resection was the optimal treatment for solid
      hemangioblastomas of the posterior fossa. For large tumors, preoperative
      embolization was critical for preventing postoperative morbidity. Given the
      improvements in microsurgical techniques and the understanding of the tumor
      vascular pattern, total tumor removal associated with a low mortality rate could
      be achieved.

PMID- 28454225
TI  - JS-K promotes apoptosis by inducing ROS production in human prostate cancer
      cells.
AB  - Reactive oxygen species (ROS) are chemical species that alter redox status, and
      are responsible for inducing carcinogenesis. The purpose of the present study was
      to assess the effects of the glutathione S transferase-activated nitric oxide
      donor prodrug, JS-K, on ROS accumulation and on proliferation and apoptosis in
      human prostate cancer cells. Cell proliferation and apoptosis, ROS accumulation
      and the activation of the mitochondrial signaling pathway were measured. The
      results demonstrated that JS-K may inhibit prostate cancer cell growth in a dose-
      and time-dependent manner, and induce ROS accumulation and apoptosis in a dose
      dependent manner. With increasing concentrations of JS-K, expression of pro
      apoptotic proteins increased, but Bcl-2 expression decreased. Additionally, the
      antioxidant N-acetylcysteine reversed JS-K-induced cell apoptosis; conversely,
      the pro-oxidant glutathione disulfide exacerbated JS-K-induced apoptosis. In
      conclusion, the data suggest that JS-K induces prostate cancer cell apoptosis by
      increasing ROS levels.

PMID- 28454224
TI  - Direct targeting of MAPK8IP1 by miR-10a-5p is a major mechanism for gastric
      cancer metastasis.
AB  - MicroRNA (miRNA) are endogenous non-coding RNAs that suppress gene expression at
      the transcriptional, post-transcriptional or translational level by targeting the
      3'-UTRs of specific mRNAs. miR-10a has been frequently reported to be aberrantly
      overexpressed in human tumors. In gastric cancer (GC), miR-10a has an important
      role in the metastasis from primary GC to lymph nodes. However, the role and
      relevant pathways of miR-10a in GC metastasis remain largely unknown. The present
      study was performed using 41 GC and 20 normal gastric mucosa tissues. Reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) analysis
      demonstrated that MAPK8IP1 was significant downregulated in GC tissue. A
      statistically significant inverse correlation was detected between miR-10a and
      MAPK8IP1 mRNA expression levels in GC specimens. Luciferase reporter assay and
      qPCR results suggested that MAPK8IP1 was a direct target of miR-10a in GC cells.
      Matrigel invasion assay and wound-healing assay results showed that MAPK8IP1
      overexpression rescued the increased migration ability of miR-10a effectors in
      MKN45 cells. Furthermore, the underlying mechanism of miR-10a functions in GC was
      explored. The findings indicated that miR-10a-5p directly targets MAPK8IP1, as a
      major mechanism for gastric cancer metastasis. The results of the present study
      suggested that miR-10a may be a potential target for the treatment of GC in the
      future.

PMID- 28454226
TI  - Long non-coding RNA HOTAIR enhances radioresistance in MDA-MB231 breast cancer
      cells.
AB  - The aim of the present study was to investigate the radiosensitizing effects of
      homeobox (HOX) transcript antisense RNA (HOTAIR) long non-coding RNA on breast
      cancer tumor cells and examine the underlying mechanisms. Recombinant plasmid
      vectors containing HOTAIR gene were constructed and MDA-MB231 cells were
      transfected with these plasmids using liposomes. The cells were treated with
      radiation and cell apoptosis, proliferation, and double-stranded DNA breaks were
      examined. HOXD10, phosphorylated AKT (p-AKT) and p-BAD expression levels were
      measured using western blot analysis. The results showed a higher expression of
      HOTAIR in advanced tumor cells. HOTAIR efficiently enhanced radioresistance in
      MDA-MB231 breast cancer cells and accelerated proliferation through the Akt
      pathway by targeting HOXD10. In conclusion, the findings demonstrated that HOTAIR
      gene is a valid therapeutic target for the reversal of radiotherapy resistance in
      breast cancer.

PMID- 28454227
TI  - Chromobox homolog 2 protein: A novel biomarker for predicting prognosis and Taxol
      sensitivity in patients with breast cancer.
AB  - Polycomb group (PcG) complexes modify histones to silence tumor suppressor genes,
      which exhibit an important function in tumorigenesis and progression. The
      chromobox (Cbx) protein family is a critical component of PcG-mediated
      repression. Cbx2, a member of the Cbx protein family, is hypothesized to exhibit
      a vital role in breast cancer. In the present study, immunohistochemical analysis
      using tissue microarrays was performed to determine the levels of Cbx2 protein
      expression in breast cancer. The association between Cbx2 expression and the
      clinical features and prognosis of 455 breast cancer patients was analyzed. In
      addition, the efficacy of Taxol was evaluated by comparing the survival of
      patients with high or low Cbx2 expression. The results revealed that Cbx2
      expression was higher in cancer tissues compared with adjacent normal tissues.
      Furthermore, high Cbx2 expression was significantly associated with large tumor
      size, lymph node metastasis, high TNM stage and positive human epidermal growth
      factor receptor-2 (HER-2) status. Patients with high Cbx2 expression also
      exhibited a shorter mean overall survival (OS) time (74.37 months) compared with
      patients with low Cbx2 expression (77.37 months). Univariate analysis indicated
      that high Cbx2 expression increased the risk of mortality by 1.826-fold compared
      with low Cbx2 expression [hazard ratio (HR), 1.826; 95% confidence interval (CI),
      1.069-3.116; P=0.027]. Among patients with high Cbx2 expression, the mean OS time
      of individuals treated with Taxol (71.01 months) was lower compared with patients
      that had not received Taxol treatment (78.43 months; log-rank test statistic,
      13.03; P<0.001). However, no significant difference in OS time was identified in
      the low expression group. The results of the current study revealed that Cbx2 may
      present a novel biomarker for predicting the prognosis of breast cancer patients.
      Cbx2 may also represent a potential target for treatment due to its important
      function in Taxol treatment responses.

PMID- 28454228
TI  - Prognostic factors of long-term outcome in surgically resectable pancreatic
      neuroendocrine tumors: A 12-year experience from a single center.
AB  - The present study was performed to assess the prognostic factors with respect to
      patient survival and clinicopathological characteristics for patients who
      underwent surgery for pancreatic neuroendocrine tumors (PNETs). A retrospective
      review of patients pathologically diagnosed with PNETs at the First Affiliated
      Hospital, Zhejiang University School of Medicine (Hangzhou, Zhejiang, China)
      between September 2002 and September 2013 was conducted. The clinicopathological
      findings, overall survival (OS) rate and disease-free survival (DFS) rate of the
      patients with PNETs were analyzed. Prognostic factors were determined by
      univariate and multivariate analyses. A total of 104 patients were selected. The
      median age at presentation was 52 years (range, 19-76 years). The most common
      surgical procedure was distal pancreatectomy (51.0%), followed by
      pancreaticoduodenectomy (27.9%) and local resection of the pancreas (16.3%). The
      majority of the tumors were of low or moderate grade (93.3%, grade 1 or 2) and
      were local or regional stage (92.3%). The 1-, 3- and 5-year OS rates were 95, 85
      and 73%, respectively. Meanwhile, the 1-, 3- and 5-year DFS rates were 86, 72 and
      68%, respectively. The OS and DFS rates were significantly different with regard
      to the grade (grades 1, 2 and 3; P<0.001) and stage (local, regional and distant
      disease; P<0.001). Furthermore, patients with a low Ki-67 index experienced
      superior OS and DFS rates compared with patients with a high Ki-67 index
      (P<0.001). The presence of lymph node metastasis was predictive of inferior OS
      and DFS rates compared with the absence of lymph node metastasis (P<0.001). OS
      rate for PNETs was significantly affected by resection margin status (P<0.001).
      In multivariable analysis, the significant factors associated with OS rate were
      stage (P=0.02), grade (P<0.001), lymph node status (P=0.025), Ki-67 index
      (P=0.031) and resection margin status (P<0.001). Meanwhile, stage (P=0.001),
      grade (P=0.017), lymph node status (P=0.02) and Ki-67 index (P=0.016) were
      prognostic factors for DFS rate. In conclusion, grade, stage, Ki-67 index and
      lymph node involvement are significant prognostic factors for OS and DFS rates in
      surgically resectable PNETs. Furthermore, surgical margin status may also be an
      independent predictor for the prognosis of PNETs. It is anticipated that these
      findings may provide useful predictors of clinical survival, particularly in the
      setting of resected disease.

PMID- 28454229
TI  - Somatostatin receptor expression indicates improved prognosis in
      gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting
      release is effective and safe in Chinese patients with advanced
      gastroenteropancreatic neuroendocrine tumors.
AB  - Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is known to overexpress
      somatostatin receptors (SSTRs), most commonly SSTR2 and SSTR5. The expression of
      SSTRs on tumor cells forms the basis for somatostatin analog treatment of
      patients with NEN. The present study detected the expression of SSTR2 and SSTR5
      in GEP-NEN and investigated the efficacy and safety of octreotide long-acting
      release (LAR) in the treatment of advanced gastroenteropancreatic neuroendocrine
      tumors (GEP-NET) in China. The present study reported that functionality of the
      pancreas, G1 and G2 grading, NET classification and Tumor-Node-Metastasis stages
      I and II were associated with higher SSTR2 positive expression. Similarly, SSTR5
      was increased in pancreatic and well-differentiated tumors. SSTR2 and SSTR5
      positive expression predicted improved survival in GEP-NEN patients. The median
      overall survival of patients treated with octreotide LAR was not reached. The
      median time to progression was 20.2 months, with the objective response rate
      being 5.6% and the stable disease rate being 79.6%. A total of 25.9% of the
      patients experienced adverse drug reactions. In conclusion, the present study
      demonstrated that SSTR2 and SSTR5 are heterogeneously expressed in GEP-NEN. Both
      markers may serve as potential prognostic factors. Octreotide LAR is effective
      and safe in the treatment of Chinese patients with advanced GEP-NET.

PMID- 28454230
TI  - A subpopulation of cancer stem cells identifies radiographic characteristics in
      glioblastoma.
AB  - Cancer stem cells (CSCs), defined by CD133 expression, harbor heterogeneous
      subpopulations of cells, including endothelial progenitor cells (EPCs). This
      study aimed to investigate whether a subpopulation of CSCs could affect the
      radiographic characteristics of glioblastoma. Tissue samples from 10 patients
      newly diagnosed with glioblastoma were selected according to the radiographic
      characteristics of their tumors. The patients were divided into two groups based
      on preoperative magnetic resonance imaging demonstrating contrast enhancement,
      necrosis and infiltrative patterns: the enhancement/necrosis group (E/N, n=5) and
      the non-enhancement/infiltration group (NE/I, n=5). Flow cytometry was used to
      assess the CSCs while immunohistochemistry was used to study microvessel density
      and the proliferation index. The EPC (CD34+/CD133+) fraction in CSCs (CD133+) was
      larger in the NE/I group. However, there was little difference in the angiogenic
      activity assessed using microvessel density between the two groups. The
      proliferation index (assessed using the antibody Ki-67) was higher in the E/N
      group and was negatively correlated with the EPC fraction. The non-EPC (CD34
      /CD133+) fraction is a major factor responsible for radiographic characteristics
      of contrast enhancement, thus establishing an association between a subpopulation
      fraction of CSCs and radiographic characteristics in glioblastoma. Therefore, the
      simple non-invasive assessment of studying contrast enhancement lesions in
      glioblastomas may be used to estimate CSC subpopulations.

PMID- 28454231
TI  - WIF-1 gene inhibition and Wnt signal transduction pathway activation in NSCLC
      tumorigenesis.
AB  - The aim of the present study is to explore the differential expression of key
      molecules associated with Wnt signaling in both clinical non-small cell lung
      cancer (NSCLC) tissue and adjacent normal lung tissue, and to discuss the
      tumorigenic role of the activation of Wnt signaling pathways in NSCLC. A total of
      52 NSCLC patients were employed in the present study. Lung cancer tissue samples
      and paracarcinoma tissue samples were obtained from these patients, who had
      undergone surgical resection of their primary cancer. The cases were diagnosed by
      hematoxylin and eosin staining. Using reverse transcription-quantitative
      polymerase chain reaction and immunohistochemical straining, the messenger RNA
      (mRNA) and protein expression levels of Wnt inhibitory factor-1 (WIF-1) and
      important molecules associated with Wnt signaling pathways were detected.
      Compared with normal tissues, a marked decreased in the mRNA and protein
      expression levels of WIF-1, and an increase in beta-catenin and cyclin D1
      expression, were observed in tumor tissues. This suggests that the activation of
      the Wnt/beta-catenin signaling pathway may be closely associated with lymph nodal
      metastasis and lower pathological classification. However, no obvious difference
      could be observed in adenomatous polyposis coli (APC) expression levels between
      lung cancer tissues and adjacent tissues to the carcinoma. The activation of the
      Wnt/beta-catenin signaling pathway in NSCLC could be initiated by WIF-1 gene
      inhibition without APC expression changes, and this may be different to the
      mechanism in other tumors.

PMID- 28454232
TI  - Philadelphia chromosome with acute myeloid leukemia and concurrent large B cell
      lymphoma of different origins: A case report.
AB  - Philadelphia chromosome with de novo acute myeloid leukemia (Ph + AML) arising
      from t(9;22) is an uncommon occurrence. Ph + AML is known to respond poorly to
      conventional chemotherapy. To the best of our knowledge, simultaneous diagnosis
      of de novo Ph + AML and lymphoma in a single patient has not yet been reported.
      The present study reports the case of a 37-year-old female patient who presented
      with bone pain, fever and lymphadenopathy, and was diagnosed as Ph + AML with
      concurrent diffuse large B cell lymphoma. Combined chemotherapy regimen covering
      AML and lymphoma was administered, achieving short-term response. However, the
      therapy soon failed and the patient succumbed to the disease. The present study
      reports the first case of Ph + AML occurring concurrently with diffuse large B
      cell lymphoma, and discusses certain differences between Ph + AML and chronic
      myelogenous leukemia in the myeloid blast crisis phase, as well as the
      appropriate therapeutic modalities for Ph + AML. In addition, the potential
      association between Ph + AML and diffuse large B cell lymphoma in this patient
      was investigated.

PMID- 28454233
TI  - Karyopherin alpha 2 expression is a novel diagnostic and prognostic factor for
      colorectal cancer.
AB  - Colorectal cancer (CRC) is the fourth most common cancer and the second leading
      cause of cancer-associated mortality in Western countries. CRC treatment is
      dependent on the preoperative and postoperative condition of patients. At
      present, the prognostic value of conventional parameters for the estimation of
      patient prognosis is limited. The aim of the present study was to investigate the
      expression of karyopherin alpha2 (KPNA2) in cancerous and healthy colon tissues
      and to evaluate the prognostic factors for patients with primary CRC. KPNA2
      expression in CRC and paired normal tissues was analyzed by immunohistochemistry
      and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In
      addition, serum KPNA2 expression was evaluated by enzyme-linked immunosorbent
      assay. Subsequently, the association between KPNA2 expression in CRC tissues and
      patient clinicopathological features was analyzed. Kaplan-Meier analysis was
      utilized to investigate the prognostic value of KPNA2 expression on overall
      survival rates following radical surgery for the treatment of CRC.
      Immunohistochemistry and RT-qPCR revealed that KPNA2 expression was significantly
      increased in CRC tissues compared with paired normal tissues. Serum KPNA2
      expression was significantly increased in CRC patients compared with healthy
      individuals. Furthermore, KPNA2 expression was observed to positively correlate
      with Tumor-Node-Metastasis stage, lymph node involvement, tumor differentiation,
      infiltration depth, lymphovascular invasion and perineural invasion, which are
      factors known to affect the prognosis of CRC patients following surgery. In
      addition, increased KPNA2 expression was associated with decreased overall
      survival and disease-free survival rates. Patients not suited for surveillance
      regimens may be identified at initial biopsy test with a positive KPNA2
      immunohistochemistry. Increased serum expression of KPNA2 may be utilized as a
      diagnostic factor for patients with CRC. High nuclear KPNA2 expression may serve
      as a novel predictor of survival following radical colorectal surgery in CRC
      patients. The results of the present study may improve individualized risk
      stratification, leading to the optimization of therapies for CRC patients.

PMID- 28454234
TI  - Gemcitabine-associated thrombotic microangiopathy in a patient with lung cancer:
      A case report.
AB  - Gemcitabine is frequently used for the treatment of a number of different cancer
      types. Gemcitabine-related thrombotic microangiopathy (TMA) has rarely been
      described, but it is a life-threatening complication. The incidence of the
      complication varies between 0.015 and 1.4%. The present study reports the case of
      a 63-year-old Caucasian male who was treated with 3 cycles of carboplatin plus
      gemcitabine, followed by 7 cycles of gemcitabine only, and developed clinical
      symptoms that, together with laboratory findings, were compatible with a
      diagnosis of hemolytic uremic syndrome TMA. The patient was admitted to Jean
      Godinot Cancer Center Institute with hemolysis, thrombocytopenia, macroscopic
      hematuria, renal dysfunction and worsening high blood pressure. Medical treatment
      for the high blood pressure, plasma infusion and hemodialysis were implemented
      without any improvement in creatine levels. The patient recovered from
      hematological disorders, left hospital and was followed-up. He required
      hemodialysis until he succumbed ~3 months subsequent to diagnosis of TMA. Even if
      thrombocytopenia, anemia and renal failure are common observations in patients
      treated by chemotherapy, clinicians should be aware of this potentially lethal
      complication. We recommend screening for TMA in such cases of anemia,
      thrombocytopenia and renal failure.

PMID- 28454235
TI  - Metabolic profiling of hepatitis B virus-related hepatocellular carcinoma with
      diverse differentiation grades.
AB  - The most effective diagnostic tool for the majority of hepatocellular carcinoma
      (HCC) patients is determining the differentiation grade of their tumors. However
      liver biopsies, which are currently the most effective way of determining tumor
      differentiation grade, have several limitations. The present study was designed
      to select serum characteristic metabolites that correlate with the
      differentiation grades of hepatitis B virus (HBV)-related HCC, and so could be
      used in the clinic as a non-invasive method of differentiating patients with
      different grades of HCC. A total of 58 patients with HBV-related HCC were
      included in the present study, and divided into three groups according to their
      tumor differentiation grade. A further 20 patients with HBV-related liver
      cirrhosis and 19 healthy volunteers were enrolled. Ultra-performance liquid
      chromatography-mass spectrometry was used to analyze endogenous metabolites.
      Multivariate statistical analysis was used to examine the data using MZmine 2.0
      software. The 14 metabolites that were highly correlated with specific
      differentiation grades of HCC were then selected for additional study. Receiver
      operator characteristic curve analysis was used to evaluate their clinical value.
      In total, 5 metabolites were finally identified, including
      lysophosphatidylcholine (16:0), oleamide, monoglyceride (0:0/15:0/0:0),
      lysophosphatidylcholine (18:0) and lysophosphatidylcholine
      [22:5(7Z,10Z,13Z,16Z,19Z)]. All these metabolites exhibited an excellent ability
      to distinguish different types of HCC with various differentiation grades and the
      area under the curve of these metabolites was up to 0.942, showing promising
      clinical value.

PMID- 28454236
TI  - Prognostic significance of CD30 expression in nasal natural killer/T-cell
      lymphoma.
AB  - The present study aimed to investigate the expression of tumor necrosis factor
      receptor superfamily member 8 (CD30) in extranodal natural killer/T-cell lymphoma
      (ENKTL) using immunohistochemistry, and to evaluate the association between CD30
      and clinicopathological and prognostic significance. CD30 expression was detected
      using immunohistochemistry on paraffin-embedded sections obtained from 122
      patients with ENKTL prior to treatment. In total, 70 of these patients with
      complete clinical data were collected for prognostic analysis. The level of CD30
      expression, of the 122 patients with ENKTL, was grouped on the basis of a 5
      tiered scale as follows: 0%, no staining; 1+, <25% positive cells; 2+, 25-50%
      positive cells; 3+, 50-75% positive cells; and 4+, >75% positive cells). In
      total, 36 (29.5%) were classified as 0; 46 (37.7%) as 1+; 22 (18.0%) as 2+; 12
      (9.8%) as 3+; and 6 (4.9%) as 4+. Among the 86 patients with scores between 1+
      and 4+, the membranous staining patterns of CD30 expression were sporadic
      (33.7%), focal (43.2%), diffuse (15.1%) and angiocentric (8.1%). When considering
      a score of >=3+ as CD30 positivity (CD30+), the CD30+ group had significantly
      shorter overall survival rates (P=0.0023) and progression-free survival rate
      (P=0.0008) compared with CD30 negative group. However, no statistically
      significant association was found between CD30 expression and clinicopathological
      features (P<0.05). The present study found that the expression of CD30 (>=3+) was
      significantly associated with poor prognosis but was not associated with clinical
      and histopathological parameters in ENKTL. Therefore, CD30 may be a useful
      prognostic marker in ENKTL.

PMID- 28454237
TI  - MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector
      domain leading to increased radiation sensitivity in lung cancer cell lines.
AB  - Lung cancer is the leading cause of cancer-associated mortality in the United
      States. Kinase hyperactivation is a known mechanism of tumorigenesis. The
      phosphorylation status of the plasma membrane-associated protein myristoylated
      alanine rich C-kinase substrate (MARCKS) effector domain (ED) was previously
      established as being important in the sensitivity of lung cancer to radiation.
      Specifically, when MARCKS ED was in a non-phosphorylated state, lung cancer cells
      were more susceptible to ionizing radiation and experienced prolonged double
      strand DNA breaks. Additional studies demonstrated that the phosphorylation
      status of MARCKS ED is important for gene expression and in vivo tumor growth.
      The present study used a peptide mimetic of MARCKS ED as a therapeutic
      intervention to modulate MARCKS phosphorylation. Culturing A549, H1792 and H1975
      lung cancer cell lines with the MARCKS ED peptide led to reduced levels of
      phosphorylated MARCKS and phosphorylated Akt serine/threonine kinase 1. Further
      investigation demonstrated that the peptide therapy was able to reduce lung
      cancer cell proliferation and increase radiation sensitivity. In addition, the
      MARCKS peptide therapy was able to prolong double-strand DNA breaks following
      ionizing radiation exposure. The results of the present study demonstrate that a
      peptide mimetic of MARCKS ED is able to modulate MARCKS phosphorylation, leading
      to an increase in sensitivity to radiation.

PMID- 28454238
TI  - Dopamine receptor D2 is correlated with gastric cancer prognosis.
AB  - It has been reported previously that a dopamine receptor D2 (DRD2) antagonist was
      able to induce cancer cell apoptosis and that DRD2 was expressed at high levels
      in pituitary adenomas. However, the expression of DRD2 in gastric cancer and its
      correlation with the prognosis of patients with gastric cancer remain to be
      elucidated. In the present study, the expression of DRD2 in 84 paired gastric
      cancer tissues and respective adjacent non-cancerous tissues were detected using
      an immunohistochemical assay. The correlation between the expression of DRD2 and
      the with survival durations of the patients with gastric cancer was analyzed
      using Kaplan-Meier analysis. In addition, online resources were utilized to
      further analyze the correlation between the mRNA expression level of DRD2 and
      prognosis. The effect of the DRD2 antagonist, thioridazine, on the proliferation
      of the AGS gastric cancer cells was determined. The results of the present study
      showed that the percentage of gastric cancer cases with a high expression level
      of DRD2 (51.2%) was higher, compared with that of cases with a low expression
      level of DRD2 (39.3%). Patients with a higher expression of DRD2 had shorter
      survival durations. The online database analysis revealed that the expression of
      DRD2 was also inversely correlated with the prognosis of patients with gastric
      cancer. Furthermore, the DRD2 antagonist, thioridazine, inhibited the growth of
      AGS gastric cancer cells. In conclusion, as the expression of DRD2 was negatively
      correlated with survival durations in patients with gastric cancer, it may be
      considered as a prognosis marker in the future. Developing DRD2 antagonists may
      assist in increasing the efficiency of cancer therapy.

PMID- 28454239
TI  - Downregulation of tumor protein 53-inducible nuclear protein 1 expression in
      hepatocellular carcinoma correlates with poor prognosis.
AB  - The expression of tumor protein 53-inducible nuclear protein 1 (TP53INP1) is
      upregulated in certain cancers and downregulated in others. However, its
      expression in hepatocellular carcinoma (HCC) is not clear. The present study
      aimed to investigate the expression and prognostic value of TP53INP1 and its
      association with clinicopathological parameters in HCC. TP53INP1 expression in
      HCC tissue samples was examined via immunohistochemistry, western blotting and
      reverse transcription-quantitative polymerase chain reaction. Expression was
      categorized as high or low. The correlations of TP53INP1 expression with clinical
      characteristics and patients' prognoses were determined. TP53INP1 was frequently
      decreased in HCC tissues compared with adjacent non-tumorous liver tissues. This
      decreased expression was significantly associated with American Joint Committee
      on Cancer stage (P=0.014) and vascular invasion (P=0.024). Kaplan-Meier analysis
      further revealed that recurrence-free survival (RFS) (P=0.001) and overall
      survival (OS) (P=0.002) were significantly worse among patients with low TP53INP1
      expression than among those with high TP53INP1 expression. In addition,
      multivariate analyses revealed that TP53INP1 was an independent predictor of OS
      [hazard ratio (HR)=2.680, 95% confidence interval (CI)=1.087-6.608, P=0.032) and
      RFS (HR=2.284, 95% CI=1.157-4.511, P=0.017). In conclusion, the expression of
      TP53INP1 was decreased in HCC, and TP53INP1 downregulation was an independent
      predictor of poor prognosis in patients with HCC.

PMID- 28454240
TI  - Squamous cell carcinoma antigen expression in tumor cells is associated with the
      chemosensitivity and survival of patients with cervical cancer receiving
      docetaxel-carboplatin-based neoadjuvant chemotherapy.
AB  - The present study examined the association between squamous cell carcinoma
      antigen (SCCA) expression and the response of patients with cervical cancer to
      docetaxel-carboplatin (DC) combination chemotherapy, in order to determine the
      prognostic potential of SCCA expression. A total of 21 patients were enrolled
      with stage IB2 or stage IIA2 SCC. Of these, 9 patients had chemotherapy-sensitive
      cancer (2 cases with a complete response and 7 cases with a partial response) and
      12 patients had chemotherapy-resistant cancer (12 cases of stable disease and no
      cases of progressive disease). Patients were treated with two cycles of DC
      chemotherapy (docetaxel 75 mg/m2 plus cisplatin 25 mg/m2) with 21-day intervals,
      followed by radical surgery. SCCA expression levels prior to and following
      chemotherapy were evaluated using immunohistochemistry. Following DC
      chemotherapy, the SCCA expression levels decreased in the patients with
      chemotherapy-sensitive cancer, but not in those with chemotherapy-resistant
      cancer (P=0.042). Significant survival differences between the SCCA-positive and 
      negative patients following chemotherapy (P=0.009) was observed. However, no
      statistically significant difference in survival between patients with
      chemotherapy-sensitive and chemotherapy-resistant cancer, or between patients
      with SCCA-positive and -negative expression prior to chemotherapy was observed.
      Overall, the chemotherapy sensitivity of patients with cervical cancer was
      associated with decreased SCCA expression levels following DC chemotherapy.
      Therefore, SCCA expression levels following DC chemotherapy may potentially be
      used in the clinical prognosis for cervical cancer patients who receive DC
      chemotherapy and subsequent radical surgery.

PMID- 28454241
TI  - Transthyretin regulates the migration and invasion of JEG-3 cells.
AB  - Preeclampsia (PE) is a pregnancy-specific disorder characterized by new-onset
      hypertension and proteinuria that occurs after 20 weeks of gestation. It involves
      several organs and continues to be a leading cause of maternal and perinatal
      morbidity and mortality worldwide. Shallow trophoblast invasion is a common
      pathological feature of PE. Transthyretin (TTR) is a 56-kDa homotetrameric
      protein that binds thyroid hormone and retinol binding protein. Dysregulated TTR
      expression has been found in cases of PE. The aim of the present study was to
      determine the functional role of TTR in the migration and invasion of JEG-3
      choriocarcinoma cells. JEG-3 cells were transfected with a plasmid construct
      expressing TTR (pCMV-Myc-TTR) or an empty plasmid (pCMV-Myc). Cell migration and
      invasion capacities were assessed by Transwell migration and invasion assays,
      respectively. These experiments demonstrated that TTR overexpression
      significantly increased the migration and invasion potential of JEG-3 cells.
      Matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases
      capable of degrading a wide range of extracellular matrix components. Western
      blot analysis revealed that TTR overexpression resulted in significantly
      increased levels of MMP2 and MMP9 in JEG-3 cells. In conclusion, our findings
      suggest an important role for TTR in regulating trophoblast invasion and
      migration, representing a possible underlying pathological and molecular
      mechanisms of PE.

PMID- 28454243
TI  - Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non
      small cell lung cancer.
AB  - Predictive biomarkers for the recurrence of non-small cell lung cancer (NSCLC) in
      patients who have received curative resection are important for cancer treatment.
      The functional microRNAs (miRNAs/miRs) in the exosomes of plasma and serum
      samples are of interest as stable and non-invasive biomarkers for recurrence in
      cancer patients. The aim of the present study was to clarify the usefulness of
      plasma exosomal miRNAs as biomarkers for the prediction of recurrence in NSCLC
      following curative resection. First, microarray-based expression profiling of
      miRNAs derived from exosomes in the plasma of 6 patients was employed to identify
      a biomarker that distinguishes between patients with and without NSCLC
      recurrence. In the miRNA microarray analyses, the exosomal miR-21 and miR-4257
      levels of the NSCLC patients showed marked upregulation in those individuals with
      recurrence compared with those without recurrence and healthy individuals. These
      two miRNAs were thus selected as recurrence-specific biomarkers and their
      potential was evaluated in a separate cohort of 195 NSCLC patients. In comparison
      to the levels in 30 healthy individuals, exosomal miR-21 and miR-4257 levels
      showed a significant increase in the NSCLC patients (P<0.01). When evaluating the
      clinicopathological significance of these miRNAs, exosomal miR-21 showed a
      significant association with tumor size and tumor-node-metastasis (TNM) stage
      (P<0.05). Exosomal miR-4257 showed a significant association with histological
      type, lymphatic invasion and TNM stage (P<0.05). The disease-free survival (DFS)
      rates of high exosomal miR-21 patients were significantly worse than those of low
      exosomal miR-21 patients (P<0.05), and the DFS rates of patients with high
      exosomal miR-4257 levels were significantly worse than those with low exosomal
      miR-4257 levels (P<0.01). In the Cox multivariate analysis, plasma exosomal miR
      21 and miR-4257 expression showed a significance association with DFS (P<0.05).
      These results suggest that plasma exosomal miR-21 and mir-4257 expression has
      potential as a predictive biomarker for recurrence in NSCLC patients who have
      received curative resection.

PMID- 28454242
TI  - Association of elevated risk of pancreatic cancer in diabetic patients: A
      systematic review and meta-analysis.
AB  - Pancreatic cancer has a five-year overall survival rate <5%, a situation that has
      not improved since for 40 years. Diabetes mellitus including type 2 diabetes
      mellitus (T2D) is a suspected risk factor for the development of pancreatic
      cancer and nearly 45% of the pancreatic cancer cases are likely to present as new
      onset diabetes cases; however, the nature of association between T2D and
      pancreatic cancer is still controversial. In this meta-analysis, we examined the
      association specifically of T2D with pancreatic cancer and the influence of
      insulin therapy. PubMed, EMBASE, Scholar, Web of Science and Scopus databases
      were searched to identify clinical and patient oriented studies that examined the
      incidence of diabetes in pancreatic cancer patients and vice versa, over the last
      10 years. All the authors independently screened the articles, and a collective
      decision was reached about the studies included in the meta-analysis. Parameters
      analyzed included, the Incidence of diabetes in pancreatic cancer patients;
      duration history of T2D in pancreatic cancer patients; influence of insulin
      therapy in T2D patients on pancreatic cancer incidence. Eleven studies with a
      total of 14,399 patients, of whom 4,080 were T2D-positive and 9,721 were non
      diabetic were included in this meta-analysis. T2D duration history was
      significantly related to pancreatic cancer incidence and insulin therapy effects.
      In conclusion, recent-onset T2D is probably a manifestation of pancreatic cancer
      whereas long-term T2D is likely a risk factor for this cancer. Insulin therapy
      appears to decrease the incidence of pancreatic cancer.

PMID- 28454244
TI  - Proliferation of sphere-forming hepatocellular carcinoma cells is suppressed in a
      medium without glucose and arginine, but with galactose and ornithine.
AB  - Resistance to sorafenib in hepatocellular carcinoma (HCC) cells exhibiting
      stemness was evaluated using a sphere formation assay. A hepatocyte selection
      medium (HSM) deficient in glucose and arginine was used to suppress the
      proliferation of cell spheres composed of HLF and PLC/PRF/5 HCC cells, which were
      subjected to a sphere formation assay. Cell spheres were cultured with sorafenib
      and subjected to a cell proliferation assay and the expression levels of
      cytochrome P450 (CYP3A4) were analyzed in RNA extracted from sphere-forming cells
      using reverse transcription-quantitative polymerase chain reaction. Sphere
      forming PLC/PRF/5 cells were more resistant to sorafenib, as compared with
      control cells, exhibiting higher expression levels of CYP3A4. When cultured in
      HSM, suppressed proliferation was observed in the sphere-forming PLC/PRF/5 cells
      and in the control cells, with no significant variation between them. The results
      suggest that deprivation of glucose and arginine is a potential novel treatment
      for HCC.

PMID- 28454245
TI  - Improving contrast enhancement in magnetic resonance imaging using 5
      aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.
AB  - Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the
      gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid
      (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells.
      In addition, fluorescence-guided resection with 5-ALA is widely used for imaging
      HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble.
      It was speculated whether converting from 5-ALA to PpIX may relatively increase
      intracellular water content, and consequently, might enhance the T2 signal
      intensity in HGG. The aim of the present study was to assess whether 5-ALA
      induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4
      patients who were candidates for HGG surgical treatment were prospectively
      analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg)
      3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images
      (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via
      fluorescence using a modified operating microscope. Fluorescent tumor tissues
      were obtained to analyze the accumulation of 5-ALA-induced PpIX within the
      tumors, which was confirmed quantitatively by high-performance liquid
      chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was
      evaluated prior to and following 5-ALA administration. Three glioblastoma
      multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the
      analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA
      induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis
      indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared
      with the AO sample. In total, 48 regions of interest were identified within the
      tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value
      within the tumors following 5-ALA administration was significantly increased
      compared with the T2 signal intensity value prior to 5-ALA administration
      (1.537+/-0.021 and 1.577+/-0.023, respectively; P=0.0055). No significant
      differences were observed in the AO group. These results suggest that the 5-ALA
      induced PpIX enhanced the T2 signal intensity in HGG. Therefore, 5-ALA may be a
      potentially useful MRI contrast reagent for HGG.

PMID- 28454246
TI  - Proliferation and motility of hepatocellular, pancreatic and gastric cancer cells
      grown in a medium without glucose and arginine, but with galactose and ornithine.
AB  - Human primary hepatocytes are able to survive in a medium without glucose and
      arginine, but supplemented with galactose and ornithine (hepatocyte selection
      medium; HSM). To address the possibility of the application of HSM in cancer
      therapy, hepatocellular carcinoma cells, pancreatic cancer cells and gastric
      cancer cells were cultured in HSM. Cell proliferation was analyzed using an MTS
      assay. Morphological changes were analyzed using hematoxylin and eosin staining.
      Apoptosis was analyzed using a TUNEL assay and cell motility was assessed with a
      scratch assay. Cell proliferation was significantly suppressed in cell lines
      grown in HSM (P<0.01 in all the cell lines). Hematoxylin and eosin staining
      revealed pyknotic nuclei, suggesting that these cells had undergone apoptosis.
      The number of TUNEL-positive cells was significantly increased in HSM. In the
      scratch assay, the distance between the growing edge and the scratched edge was
      significantly lower (P<0.01 in all the cell lines) in cells cultured in HSM,
      compared with those grown in Dulbecco's modified Eagle's medium or RPMI-1640.
      Therefore, the proliferation and motility of hepatocellular carcinoma cells,
      pancreatic cancer cells and gastric cancer cells was suppressed, and these cells
      subsequently underwent apoptosis in a medium without glucose and arginine, but
      containing galactose and ornithine.

PMID- 28454247
TI  - AMPD3 is associated with the malignant characteristics of gastrointestinal
      stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the
      gastrointestinal tract. It is well known that activating mutations in the
      receptor tyrosine kinases KIT and platelet-derived growth factor receptor-alpha
      have essential roles in the pathogenesis of GISTs. The activation of these
      receptor protein kinases triggers multiple signaling pathways that promote cell
      proliferation and survival; however, the exact mechanism by which the activation
      of these kinases promotes the progression of GISTs remains uncertain. The aim of
      the present was to search for genes that are associated with the progression of
      GIST. The present study used reverse transcription-quantitative polymerase chain
      reaction to demonstrate that adenosine monophosphate deaminase 3 (AMPD3) was
      highly expressed in GISTs. Furthermore, transfection of GIST-T1 cells with KIT
      specific small interfering RNA (siRNA) demonstrated that the expression of AMPD3
      was dependent on KIT expression, while the depletion of AMPD3 in human GIST-T1
      cells using AMPD3-specific siRNA resulted in the suppression of cell migration
      and invasion. In addition, AMPD3 depletion sensitized GIST-T1 cells to the
      tyrosine kinase inhibitor imatinib. The results of the present suggested that the
      combined inhibition of tyrosine kinases and AMPD3 may be effective for the
      treatment of GISTs.

PMID- 28454248
TI  - Primary bone mantle cell lymphomas with multiple vertebral compression fractures:
      A case report.
AB  - Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma. Patients with
      MCL generally present with extensive lymphadenopathy and extranodal involvement.
      To the best of our knowledge, no cases of primary bone MCL with multiple
      vertebral compression fractures have been reported in the literature thus far.
      The current study reports the case of a 75-year-old Chinese male patient
      presenting with lower back pain for 1 year. B symptoms were not observed in the
      patient's medical history. X-ray revealed osteoporosis, and mixed osteolytic and
      osteosclerotic lesions in the T10 and L1 vertebrae with decreased height.
      Computed tomography of the spine showed multiple vertebral compression fractures,
      particularly at T10 and L1. Furthermore, magnetic resonance imaging demonstrated
      a diffuse homogeneous abnormal signal with multiple vertebral compression
      fractures. The patient underwent vertebral biopsy and percutaneous balloon
      kyphoplasty. Histopathological examination of the biopsy revealed abnormal,
      diffuse, atypical, small-sized, slightly irregular lymphocytes with condensed
      chromatin. Immunohistochemical staining showed CD5+, CD20+ and cyclin D1+. Thus,
      the patient was diagnosed with primary bone MCLs and chemotherapy was
      administered. During the 2-month follow-up, the patient remained in a good
      clinical condition. The present study reports a rare case of primary osseous MCL
      and a review of the literature.

PMID- 28454249
TI  - Six1 expression is associated with a poor prognosis in patients with glioma.
AB  - Glioma is the most common human brain cancer and has poor prognosis. Messenger
      RNA profiling identified that sineoculis homeobox homolog 1 (Six1) is
      dysregulated in glioma tumor progenitor cells from glial progenitor cells
      isolated from normal white matter. However, the expression and role of Six1 in
      glioma remains unclear. The purpose of the present study was to investigate the
      expression level of Six1 in glioma tissues and the association between Six1
      expression and clinicopathological characteristics and prognosis of gliomas. The
      Six1 protein was detected by immunohistochemistry in 163 glioma tissues of
      distinct malignancy grades, and Kaplan-Meier survival analysis was performed to
      assess the prognosis of the patients. The Six1 protein was stained in 49.1% (80
      out of 163) of the glioma tissues, including 34.2% of low-grade [World Health
      Organization (WHO) I/II] gliomas and 80.8% of high-grade (WHO III/IV) gliomas.
      Normal brain tissues rarely expressed the Six1 protein. In addition, Six1
      expression was significantly associated with WHO grade (P<0.001). According to
      the log-rank test and Cox regression model, Six1 may be suggested as an
      independent prognostic factor, in addition to the WHO grade. Overall, Six1
      protein expression varies between different grades of glioma and is associated
      with the WHO grade. Upregulation of Six1 is more frequent in high-grade glioma
      and is an independent prognostic factor of poor clinical outcome.

PMID- 28454250
TI  - Intensity modulated radiation therapy to treat primary female mediastinal
      seminoma and massive pericardial effusion: A case report.
AB  - Primary mediastinal seminoma is a rare extragonadal germ cell tumour that mainly
      occurs in males. The present study reports the case of a 27-year-old woman that
      presented with superior vena cava syndrome and a large mass in the mediastinum,
      which was diagnosed as primary female mediastinal seminoma. The patient received
      6 cycles of cisplatin-based chemotherapy [4 cycles BEP chemotherapy (120 mg
      cisplatin, 0.45 g etoposide and 60 mg bleomycin, once every 3 weeks); 2 cycles
      IEP chemotherapy (120 mg cisplatin, 100 mg epirubicin and 6 g ifosfamide, once
      every 3 weeks)] and the patient showed an increase in the size of the mediastinal
      mass and hydropericardium, indicating a resistance to chemotherapy. Radiotherapy
      to the mediastinum (50 Gy over 18 fractions) and pericardium (30 Gy over 18
      fractions) was performed. Following radiotherapy, the patient was considered to
      have a complete response to the treatment, and subsequent to a 5-year follow-up,
      no recurrence or metastasis was identified. To the best of our knowledge, no
      similar cases have been reported in the literature at present.

PMID- 28454251
TI  - Laparoscopic resection of a sigmoid colon lipoma in a young female patient: A
      case report and review of the literature.
AB  - Lipomas of the sigmoid colon are rare entities. The present case describes a 27
      year-old Caucasian woman who underwent a laparoscopic sigmoidectomy following the
      detection of a giant lipoma. The young patient was referred to the Emergency
      Department of the University Hospital of Heraklion (Crete, Greece) in May 2013
      after experiencing intermittent abdominal cramping during defecation, and
      altering episodes of diarrhea and constipation. In addition, the patient
      described the protrusion of a solid tissue mass shaped like a 'champagne bottle
      cork' from the anus following defecation. These symptoms had been present for 1
      month prior to referral. Physical examination was unremarkable. An urgent
      colonoscopy revealed a polypoid lesion measuring 2.5 cm in diameter in the
      sigmoid colon, which was located ~12 cm above the anal ring, with a smooth
      surface and tissue fragility. Tissue samples were obtained and sent for
      histopathological analysis. Preoperative contrast-enhanced computed tomography
      was performed urgently and confirmed the presence of a solid mass in the sigmoid
      colon without enlargement of regional lymph nodes. Following adequate
      preparation, the patient underwent a laparoscopic sigmoidectomy with
      intracorporeal termino-terminal colorectal anastomosis, with the use of a
      circular stapler. The patient had a positive post-operative outcome without
      complications and was discharged on day 4 post-surgery in an optimal condition.
      Histopathological examination of the surgical specimen demonstrated a
      pedunculated lipoma shaped like a 'champagne bottle cork'. The tumor consisted of
      mature adipose cells. The overlying colonic mucosa showed hyperplastic crypts
      with regenerative changes. In the lamina propria mild inflammatory infiltration
      was observed. At 2 years post-surgery, the patient remains asymptomatic without
      any clinical evidence of recurrence.

PMID- 28454252
TI  - Multifactorial neutropenia in a patient with acute promyelocytic leukemia and
      associated large granular lymphocyte expansion: A case report.
AB  - Neutropenia in the setting of acute hematological malignancies may impact disease
      prognosis, thus affecting therapy dose intensity. This is often due to
      chemotherapy-induced aplasia as well as to the disease itself. However, chronic
      neutropenia deserves further investigation, as the management of reversible
      concomitant causes may avoid treatment delay. The present study describes a case
      of an acute promyelocytic leukemia patient with chronic severe neutropenia of
      multifactorial origin, including acute leukemia itself, chemotherapy, autoimmune
      activation with anti-platelets and anti-neutrophil antibodies positivity, and the
      rare association of large granular lymphocyte (LGL) expansion. As neutropenia may
      challenge the diagnosis and treatment of acute malignancies, clinicians and
      hematopathologists must discuss the differential diagnosis in order to avoid
      misdiagnosing and undertreating concomitant diseases. In particular, LGL chronic
      expansion and autoimmunity should be considered.

PMID- 28454253
TI  - Expression and clinical significance of YAP in laryngeal squamous cell carcinoma
      patients.
AB  - The aim of the present study was to investigate the expression levels of Yes
      associated protein (YAP) in different grades of laryngeal squamous cell carcinoma
      (LSCC) tissues and vocal cord polyps tissues, and to investigate any correlations
      with clinical factors. The expression of YAP in 128 cases of LSCC and 10 cases of
      vocal cord polyps tissues was tested using immunohistochemistry. YAP was
      primarily present in the nucleus of LSCC and controls, whereas phosphorylated YAP
      expression was present in the cytoplasm. The results indicated that YAP
      expression was upregulated in LSCC samples compared with vocal cord polyps
      tissues. YAP expression was positively correlated with the malignant degree of
      LSCC (P<0.01) and a high level of YAP expression in LSCC tissues was correlated
      with pathological type, lymphatic metastasis and clinical stage. The present
      study provided evidence for the expression and localization of YAP in LSCC and
      vocal cord polyps tissues. Thus, YAP may be involved in the occurrence and
      development of LSCC as an oncogene.

PMID- 28454254
TI  - Oculomotor nerve palsy as a preceding symptom of adult sporadic Burkitt lymphoma:
      A case report and review of the literature.
AB  - Adult sporadic Burkitt lymphoma (BL) is a rare aggressive neoplasm and represents
      ~1-5% of all lymphomas diagnosed in adults. The disease exhibits an aggressive
      clinical manifestation, which frequently involves the central nervous system
      (CNS) in the early stages, and is usually accompanied by abnormalities in
      cerebrospinal fluid (CSF) examinations and/or neuroradiography. The current study
      describes the rare case of a 29-year-old man who presented with oculomotor nerve
      palsy without palpated masses, B symptoms, peripheral blood anomaly and
      abnormalities of the nervous system. The patient was initially misdiagnosed with
      abducens diplopia, but was subsequently confirmed to have BL with early CNS
      invasion. Epstein-Barr virus and human immunodeficiency virus infection were
      negative. Intensive systemic chemotherapy with hyperfractionated
      cyclophosphamide, vincristine, therarubicin and dexamethasone (hyper-CVAD,
      cyclophosphamide 600 mg/m2 on days 2-4; vincristine 1.4 mg/m2 on days 5 and 12,
      therarubicin 50 mg/m2 on day 5 and dexamethasone 40 mg on days 2-5 and 12-15),
      including intrathecal chemotherapy with methotrexate (5 mg), arabinocytidine (5
      mg) and dexamethasone (5 mg), was determined as an appropriate treatment.
      Rituximab (375 mg/m2 on day 1) was administered alongside chemotherapy to
      increase treatment efficacy. The patient temporarily underwent complete
      remission, but subsequently relapsed as no suitable bone marrow donor was
      available. Adult sporadic BL with early CNS invasion, which traditional tests
      such as neuroradiography and CSF examination fail to identify, is uncommon.
      Therefore, appropriate diagnostic tests are critical for accurate diagnosis and
      must be performed immediately, particularly in patients that present with unusual
      image and laboratory manifestations.

PMID- 28454255
TI  - miR-219-5p suppresses the proliferation and invasion of colorectal cancer cells
      by targeting calcyphosin.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs involved in an array of biological
      processes, and their dysregulation is associated with tumor development and
      progression. One such miRNA, miR-219-5p, is abnormally expressed in patients with
      colorectal cancer (CRC). In the present study, reverse transcription-quantitative
      polymerase chain reaction was performed to measure miR-219-5p expression in cells
      from both CRC tumors, and surrounding healthy tissue. MTT and invasion assays
      were used to determine the role of miR-219-5p in regulating CRC cell
      proliferation and invasion, respectively. A luciferase assay was then performed
      to assess the binding of miR-219-5p to the CAPS gene that encodes calcyphosin
      protein. The present study confirmed that miR-219-5p expression is significantly
      downregulated in CRC tissue. miR-219-5p knockdown promoted the growth of HCT-8
      cells and increased the expression of calcyphosin protein (CAPS). On the other
      hand, overexpressing miR-219-5p inhibited HCT-8 cell growth and invasion, and
      downregulated CAPS expression. In addition, CAPS was identified as the functional
      downstream target of miR-219-5p by directly targeting its 3'-untranslated region.
      Therefore, miR-219-5p may function as a tumor suppressor by decreasing CAPS
      expression, and subsequently inhibit tumor proliferation and invasion. These
      results indicate that novel therapeutic strategies that increase miR-219-5p
      expression may be developed to treat CRC.

PMID- 28454256
TI  - High expression of MMP9 in glioma affects cell proliferation and is associated
      with patient survival rates.
AB  - Human gliomas are a heterogeneous group of primary malignant brain tumors, which
      most commonly occur in the central nervous system of children and adults.
      Previous studies have suggested a prognostic role of matrix metalloproteinase 9
      (MMP9) in glioma, however, the frequency and significance of the protein
      expression of MMP9 in glioma remain to be fully elucidated. In the present study,
      the expression of MMP9 was detected by reverse transcription-quantitative
      polymerase chain reaction (qPCR), western blotting and immunohistochemical
      staining. MTT and colony-forming assays were used to detect the role of MMP9 in
      the proliferation of glioma cells. MMP9 copy numbers in glioma were examined
      using qPCR. The results indicated that the expression level of MMP9 was
      significantly increased in glioma and was associated with World Health
      Organization (WHO) glioma grades. The high expression of MMP9 in tissues was an
      independent predictor of survival rates in patients with WHO grade III tumors.
      The overexpression of MMP9 promoted cell growth and induced a significant
      increase in clonogenic potential in U87 glioblastoma cell lines. These
      experimental data suggested that the overexpression of MMP9 in glioblastoma cells
      may occur primarily through an increase in gene copy number. The results of the
      present study suggested that the overexpression of MMP9 may be necessary for the
      transition to the more aggressive phenotype typical of WHO grade III gliomas,
      suggesting the likely involvement of the MMP9 gene in gliomagenesis and disease
      progression.

PMID- 28454257
TI  - Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation of the
      ureter: A case report and review of the literature.
AB  - Sarcomatoid urothelial carcinoma of the urinary tract is associated with poor
      prognosis. The majority of sarcomatoid urothelial carcinomas are found in the
      urinary bladder, while a small minority have been shown to arise from the ureter.
      In the present case, a 72-year-old male patient was diagnosed with sarcomatoid
      urothelial carcinoma with chondrosarcomatous differentiation of the left ureter,
      and subsequently underwent nephroureterectomy and retroperitoneal lymph node
      dissection. Two lymph nodes from the renal hilum and one paraaortic lymph node
      were also found to have metastatic involvement; however, the patient refused to
      receive chemotherapy or radiotherapy and succumbed to bone and omentum metastasis
      at 6 months after the initial diagnosis. Sarcomatoid urothelial carcinoma of the
      ureter is uncommon. Even rarer is the presence of malignant heterologous
      elements, such as chondrosarcoma. The present study reports a rare case of
      sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation of the
      ureter, as well as a review of the literature, in order to demonstrate the
      aggressive nature of this particular malignancy.

PMID- 28454258
TI  - Locally advanced paranasal sinus carcinoma: A study of 30 patients.
AB  - Sinonasal carcinomas (SNcs) are rare neoplasms arising from the paranasal sinuses
      and nasal cavity. Although these tumours have a heterogeneous histology, they are
      commonly diagnosed as a locally advanced disease and are associated with a poor
      prognosis. The present retrospective study reviewed 30 patients with locally
      advanced SNc, who were treated with surgery followed by chemoradiotherapy or
      radiotherapy, or radiotherapy with or without concomitant chemotherapy between
      January 1999 and January 2013 at the Department of Radiation Therapy, University
      of Naples 'Federico II' (Naples, Italy). A total of 19 patients were treated with
      upfront surgery followed by adjuvant radio- or chemoradiotherapy (group A), while
      the remaining 11 patients received exclusive radiotherapy with or without
      concomitant chemotherapy (group B). Concurrent cisplatin-based chemotherapy (100
      mg/m2, days 1, 22 and 43 for 3 cycles) was administered to 34% of patients in
      group A and 55% of patients in group B. At a median follow-up of 31 months, 33.3%
      of patients were alive. Cause-specific survival (CSS) and progression-free
      survival (PFS) times were 32 and 12 months, respectively. No difference in CSS
      rate was observed between the two treatment groups. Univariate analysis
      determined that disease stage was the only factor that significantly affected CSS
      (P=0.002) and PFS (P=0.0001) rates. Acute and chronic toxicities were mild, with
      only 23.3% of patients reporting G1-2 side effects and no treatment-related
      blindness. The present study reported moderate activity and efficacy of surgery
      followed by adjuvant radio- or chemoradiotherapy, and exclusive radiotherapy with
      or without chemotherapy in this poor prognosis category of patients.

PMID- 28454259
TI  - Intentional marginal resection of periosteal osteosarcoma in combination with
      neoadjuvant chemotherapy: A report of two cases and a review of the literature.
AB  - A wide resection of the tumor with or without chemotherapy is the treatment of
      choice for periosteal osteosarcoma (PO) of the extremities, however, post
      operative limb function and quality of life could be compromised. The present
      study reports two cases of 14-year-old boys who presented with progressively
      enlarging masses in their right knee regions. Computed tomography and magnetic
      resonance imaging scans indicated a fusiform space-occupying mass encircling the
      bone cortex, with stippled calcification. A diagnosis of PO was suspected. The
      histological findings confirmed the diagnosis of intermediate PO. Pre-operative
      chemotherapies were started, and good responses were detected by clinical
      evaluation and histological findings. Surgeries preserving the functional
      structures, including neurovascular bundles, tendons, muscles and epiphyses, were
      performed, followed by routine chemotherapy. The two patients experienced disease
      free survival with follow-up times of 37 and 108 months, respectively. The
      patients were satisfied with the results of the treatment and they returned to
      normal life activities. These two cases indicated that a marginal resection of
      the tumor in conjunction with effective neoadjuvant chemotherapy may be an ideal
      alternative treatment for intermediate PO, since survival along with well
      preserved limb function could be guaranteed. By contrast, a wide excision could
      result in the loss of limb function.

PMID- 28454260
TI  - K9(C4H4FN2O2)2Nd(PW11O39)2.25H2O induces apoptosis in human lung cancer A549
      cells.
AB  - Lung cancer is the leading cause of cancer-associated mortality worldwide. The
      present study investigated the effects of K9(C4H4FN2O2)2Nd(PW11O39)2.25H2O
      (FNdPW), a chemically synthesized polyoxometalate that contains rare earth
      elements, on lung cancer growth, and explored the mechanism underlying its
      actions. The effects of FNdPW on the cell viability and apoptosis of human lung
      cancer A549 cells were measured using MTT assay, acridine orange/ethidium bromide
      staining and electron microscopy. The expression of apoptosis-related proteins,
      including B-cell lymphoma (Bcl)-2-associated death promoter (Bad), phosphorylated
      (p)-Bad, X-linked inhibitor of apoptosis (XIAP), apoptosis-inducing factor (AIF),
      Bcl-2-associated X protein (Bax) and Bcl-2, was determined by western blotting.
      Caspase-3 activity was measured using a caspase-3 activity kit. After 72 h of
      incubation, FNdPW reduced cell viability and induced apoptosis in A549 cells in a
      concentration- and time-dependent manner. FNdPW upregulated the pro-apoptotic Bad
      and Bax proteins, and downregulated the anti-apoptotic p-Bad, Bcl-2 and XIAP
      proteins. Furthermore, FNdPW also enhanced caspase-3 activity and increased the
      protein level of AIF in A549 cells, which was independent of the caspase-3
      pathway. These events were associated with the regulation exerted by FNdPW on
      multiple targets involved in A549 cell proliferation. Therefore, FNdPW may be a
      novel drug for the treatment of lung cancer.

PMID- 28454261
TI  - Clinical significance of ADAM10 expression in laryngeal carcinoma.
AB  - Recent findings suggest that upregulated a disintegrin and metalloproteinase
      (ADAM)10 expression participates in the progression of multiple types of cancer.
      However, the expression pattern and clinicopathological significance of ADAM10,
      and its potential prognostic role in laryngeal carcinoma remains to be explored.
      The present study firstly determined the significantly elevated expression status
      of ADAM10 protein and messenger RNA in laryngeal carcinoma tissues compared with
      that in adjacent non-tumor tissues by western blotting and reverse transcription
      quantitative polymerase chain reaction analysis. Next, the expression of ADAM10
      and the proliferation marker Ki-67 was examined in 78 laryngeal carcinoma and 35
      adjacent non-tumor specimens using immunohistochemistry. Overexpressed ADAM10 in
      laryngeal carcinoma was detected, which correlated with T classification
      (P<0.01), clinical stage (P<0.01), pathology (P=0.034) and Ki-67 expression
      (P<0.01). Furthermore, the expression of ADAM10 was positively correlated with
      the expression of Ki-67 (R2=0.22; P<0.01). The Kaplan-Meier method revealed that
      the group with overexpressed ADAM10 exhibited shorter overall survival time
      compared with those with low ADAM10 expression. Our findings indicated that
      ADAM10 serves a notable role in the progression and prognosis of laryngeal
      carcinoma.

PMID- 28454262
TI  - Aberrant KLK4 gene promoter hypomethylation in pediatric hepatoblastomas.
AB  - DNA methylation has a crucial role in cancer biology and has been recognized as
      an activator of oncogenes and inactivator of tumor suppressor genes, both of
      which are mechanisms for tumorigenesis. Kallikrein-related peptidase 4 (KLK4),
      has been suggested to be an oncogene in various types of cancer. The aim of the
      present study was to assess the DNA methylation patterns of the KLK4 gene in
      cancerous samples harvested from patients with hepatoblastoma (HB). KLK4 mRNA
      expression levels were detected using reverse transcription-quantitative
      polymerase chain reaction and assessed its DNA methylation patterns using high
      throughput mass spectrometry on a matrix-assisted laser desorption/ionization
      time-of-flight mass array. A total of 10 HB and 10 normal liver tissue samples
      were obtained from patients with HB. The results of the present study showed that
      a significantly higher level of KLK4 mRNA expression levels were detected in HB
      tissues, as compared with the matched controls. Furthermore, the KLK4 gene
      promoter region was distinctively less methylated in the HB samples compared with
      the controls and negatively correlated with KLK4 mRNA expression levels. These
      findings indicate that aberrant methylation of KLK4 may contribute to its
      upregulated mRNA expression in HB.

PMID- 28454263
TI  - Investigation of the cytotoxicity, apoptosis and pharmacokinetics of Raddeanin A.
AB  - Raddeanin A, one of the triterpenoid saponins extracted from Anemone raddeana
      rhizome of the Ranunculaceae family, has demonstrated the ability to inhibit the
      growth of human hepatic and gastric cancer cells. However, the effects of
      Raddeanin A on human colon cancer cells have not been investigated extensively.
      The present study aimed to examine the antiproliferative and apoptosis-inducing
      effects of Raddeanin A on the HCT-116 human colon cancer cell line in vitro, and
      evaluate the pharmacokinetic and biodistribution properties of Raddeanin A in
      mice following a single oral administration. A 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay was used to assess the in vitro cytotoxicity of
      Raddeanin A against HCT-116 cells. 4',6-Diamidino-2-phenylindole, dihydrochloride
      staining and flow cytometry were performed to further examine the apoptosis
      inducing capability of Raddeanin A. The concentrations of Raddeanin A in the
      plasma and tissues were analyzed using liquid chromatography-tandem mass
      spectrometry. Raddeanin A showed a dose-dependent antiproliferative effect
      towards the HCT-116 cells, with a half maximal inhibitory concentration of ~1.4
      uM. Treatment with Raddeanin A resulted in a significant induction of apoptosis,
      observed as apparent morphological changes of the nuclei, with a total apoptotic
      ratio of 41.8% at a concentration of 3 uM. Low concentrations of Raddeanin A were
      detected in the heart, liver, spleen, lung, kidney and plasma of the mice
      following oral administration, however, the majority of the Raddeanin A was
      distributed in the intestinal tract, particularly in the colon and caecum. These
      present study confirmed the growth-inhibitory and apoptosis-inducing effects of
      Raddeanin A on HCT-116 cells and performed preliminary examinations of its
      pharmacokinetic properties, which provide a foundation for further investigating
      the inhibitory mechanism on the colon cancer cells in vivo.

PMID- 28454264
TI  - Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and
      migration in leukemia cells.
AB  - Ribosomal S6 kinases (RSKs) are directly regulated by extracellular signal
      regulated kinase (ERK) signaling and are implicated in cell growth, survival,
      motility and senescence. The present study observed that RSK1 was overexpressed
      in primary untreated leukemia patient bone marrow samples compared with the
      expression at the complete remission stage, using reverse transcription
      quantitative polymerase chain reaction (RT-qPCR). In addition, a high RSK1
      expression (relative expression >=10) was associated with a significantly shorter
      overall survival (P=0.038) compared with that in patients with low RSK1
      expression (relative expression <10). The current study also investigated the
      effect of luteolin, a novel p90 ribosomal S6 kinase (RSK) inhibitor extracted
      from Reseda odorata L., which shows strong biochemical functions including anti
      allergy, anti-inflammation and anti-cancer functions, in MOLM-13 and Kasumi-1
      leukemic cells. The cell viability, apoptosis and migration ability analysis were
      assessed by performing a cell counting kit-8 assay, Annexin V-FITC/PI double
      staining and migration filter assay, respectively. The results indicated that
      luteolin inhibited the growth of the leukemic cell lines through induction of
      apoptosis, while the migration ability was also suppressed. Overexpression of
      RSK1 by plasmid transfection was found to decrease the luteolin-induced apoptosis
      and migration capabilities. By contrast, knockdown of the RSK1 expression by
      small interfering RNA appeared to induce the same effect as luteolin on MOLM-13
      and Kasumi-1 leukemic cells. In conclusion, these results suggest that luteolin
      inhibits leukemic cell proliferation and induces apoptosis by inhibition of the
      RSK1 pathways.

PMID- 28454265
TI  - Downregulation of RASAL2 promotes the proliferation, epithelial-mesenchymal
      transition and metastasis of colorectal cancer cells.
AB  - RAS protein activator like 2 (RASAL2) is a RAS-GTPase-activating protein and has
      recently been identified to be a tumor suppressor in various types of human
      cancer; however, the function of RASAL2 in colorectal carcinoma (CRC) remains
      unclear. In the present study, the function of RASAL2 in CRC cells was
      investigated using a RASAL2 loss-of-function cell model. RASAL2 short hairpin RNA
      was transfected into the human CRC cell lines LoVo, SW620 and HCT116, and the
      wild-type colon cell line NCM460. The subsequent downregulation of RASAL2 was
      evaluated using western blot and reverse transcription-quantitative polymerase
      chain reaction analyses. It was observed that RASAL2 expression was significantly
      decreased in human CRC tissues and cell lines (P<0.01). In the loss-of-function
      cell models, RASAL2 expression was decreased significantly, while cell
      proliferation, colony formation, migration and invasion were increased (all
      P<0.01). These effects were associated with the induction of epithelial
      mesenchymal transition and Raf/mitogen-activated protein kinase hyperactivation.
      The results of the present study indicate that RASAL2 is a potential therapeutic
      target to inhibit CRC progression and metastasis.

PMID- 28454266
TI  - MicroRNA-146a affects the chemotherapeutic sensitivity and prognosis of advanced
      gastric cancer through the regulation of LIN52.
AB  - The present study aimed to evaluate the correlation between the expression of
      microRNA-146a (miR-146a) and its target gene, LIN52, in advanced gastric cancer,
      and determine their potential effects on chemotherapeutic sensitivity and
      prognosis. Total RNA was extracted from 93 tissue samples of advanced gastric
      cancer and corresponding adjacent non-tumor tissues to quantify the relative
      expression levels of miR-146a using reverse transcription-quantitative polymerase
      chain reaction analysis. The expression of LIN52 was detected in tumors and
      normal tissues using immunohistochemical analysis. Correlation analysis was
      performed to assess the correlation between the expression of miR-146a and LIN52
      and clinicopathological parameters of gastric cancer, including clinical
      diagnostic specificity, clinical tumor-necrosis-metastasis staging, lymph node
      metastasis, differentiation grade, chemotherapeutic sensitivity and prognosis.
      The expression of miR-146a in advanced gastric cancer tissues was lower, compared
      with that in the adjacent non-tumor tissues, and was negatively correlated with
      lymph node metastasis (P<0.05). Gastric cancer tissues with a low expression
      level of miR146a exhibited an increased expression level of LIN52 (P<0.05).
      Receiver operating characteristic curve regression analysis showed that miR-146a
      had 98% sensitivity in distinguishing gastric cancer tissues and adjacent non
      tumor tissues. A high expression of miR-146a in gastric cancer was associated
      with improved treatment efficacy in patients. The chemotherapeutic sensitivity of
      patients with tumors expressing high levels of miR-146a was significantly higher,
      compared with that of patients with tumors expressing low levels of miR-146a
      (P<0.05). The expression of miR-146a was low in advanced gastric cancer tissues.
      As a tumor suppressor gene in advanced gastric cancer, miR-146a had a significant
      negative correlation with LIN52. High expression levels of miR-146a in advanced
      gastric cancer tissue may be associated with improved treatment efficacy of
      chemotherapy, suggesting that miR-146a may be a molecular marker for the
      diagnosis, prediction of treatment efficacy and prognosis of advanced gastric
      cancer.

PMID- 28454267
TI  - Characteristics and outcome of laryngeal squamous cell carcinoma in young adults.
AB  - Laryngeal carcinoma rarely occurs in the young adult population. Therefore, the
      optimal treatment for this age group is unclear, specifically regarding organ
      preservation treatment. In order to assess the distinct characteristics of
      laryngeal squamous cell carcinoma (SCC) in young adults and describe the effect
      of treatment on survival, a retrospective chart review of all patients aged <40
      years, who were treated in a tertiary referral center for laryngeal SCC between
      January 1960 and December 2013, was performed. Patients who were treated prior to
      and following the Veterans study, representing an arbitrary point which started
      the organ preservation era, were compared. A total of 29 patients (male:female
      ratio, 2.6:1) were identified. The mean age at diagnosis was 35+/-5 years and 17
      patients (59%) were smokers. In total, 12 (41%) of patients were stage I, 4 (14%)
      were stage II, 8 (28%) were stage III and 5 (17%) were stage IV. Glottic tumors
      were present in 20 (69%) of patients and supraglottic tumors in 6 (21%); the site
      of tumor origin could not be determined in 3 (10%) of patients. Surgery was
      performed in 11 (38%) of patients, radiation in 21 (72%) and chemotherapy in 5
      (17%). A comparison between patients treated prior to and following the Veterans
      study demonstrated a 2-year higher laryngectomy-free survival rate of 53% and
      78%, respectively (P=0.299). The 2-year disease-free survival rate was 93% for
      patients who were treated prior to the Veterans study and 71% for patients who
      were treated after (P=0.001), with no significant change in overall survival
      (P=0.413). The results suggest that the characteristics and behavior of laryngeal
      carcinoma in young adults is similar to older adults. Higher rates of 2-year
      laryngectomy-free survival were noted in patients treated following the organ
      preservation era with no significant difference in survival compared with
      patients who were treated before.

PMID- 28454268
TI  - TCRP1 expression is associated with platinum sensitivity in human lung and
      ovarian cancer cells.
AB  - Platinum-based drugs, including cisplatin (DDP) and oxaliplatin (L-OHP), are
      among the most potent chemotherapy drugs, and are widely utilized for the
      treatment of human lung and ovarian cancer. However, certain patients do not
      respond to platinum-based agents, and even those who initially benefit from the
      treatment will eventually exhibit resistance to these drugs. Although certain
      factors have been investigated for their potential to predict platinum
      resistance, more effective predictors for the improved management of patients
      with lung and ovarian cancer are required. Tongue cancer resistance-associated
      protein 1 (TCRP1) is a newly identified gene, which was cloned from a multi-drug
      resistant cell line of tongue cancer. Previous data has shown that TCRP1 is able
      to mediate DDP resistance in human oral squamous cell carcinoma cells. However,
      the contribution of TCRP1 to the resistance of platinum agents in human lung and
      ovarian cancer cells remains to be elucidated. Our previous study showed that
      TCRP1 expression levels in samples of lung and ovarian cancer were significantly
      increased compared with normal controls. In the present study, it was
      demonstrated that TCRP1 contributed to the resistance to DDP and L-OHP in human
      lung and ovarian cancer cells. Knockdown of TCRP1 resensitized the cells to the
      platinum-based agents. The present study identified a positive correlation
      between TCRP1 expression and primary resistance to DDP and L-OHP in lung cancer
      cells. In addition, it was observed that cells treated with nuclear factor (NF)
      kappaB inhibitor BAY 11-7082 displayed increased sensitivity to DDP and L-OHP.
      The results of the present study suggested that TCRP1 may be associated with
      resistance to DDP and L-OHP in lung and ovarian cancer cells, and the Akt/NF
      kappaB signaling pathway may be involved in the functioning of TCRP1. These
      findings identify TCRP1 as a potential predictor of platinum resistance in the
      treatment of lung and ovarian cancer.

PMID- 28454269
TI  - Bone marrow-derived dendritic cells under influence of experimental breast cancer
      and physical activity.
AB  - Immune cells are required in the immune response against tumours, although
      sometimes without success. The present study aimed to investigate dendritic cell
      (DC) maturation in animals with induced immunosuppression that were subjected to
      physical activity (PA). Immunosuppression was induced using 7,12-dimethyl
      benzanthracene (DMBA). A total of 56 Balb/c mice were divided into four groups,
      including the control group, non-DMBA administered/PA group (GII), DMBA
      administered/non-PA group (GIII) and the DMBA administered/PA group (GIV). Bone
      marrow was removed from the leg bones following sacrifice. Bone marrow-derived
      DCs were stimulated to differentiate by granulocyte-macrophage colony-stimulating
      factor, interleukin (IL)-4 and tumour necrosis factor-alpha, after which the
      phenotype was assessed by flow cytometry and the cytokine profile was assessed
      using ELISAs. PA significantly increased the percentage of DCs in GII (55.38+/
      2.63%) and GIV (50.1+/-3.1%) mice, as compared with GI (34.61+/-1.28%) and GIII
      (36.25+/-1.85%) mice (P<0.05). In addition, GIV mice showed a significantly
      higher level of cluster of differentiation (CD) 80+/CD86+ DCs (76.38+/-6.31%), as
      compared with GI (54.03+/-6.52%) and GIII (52.07+/-5.74%) mice (P<0.05).
      Furthermore, GIV mice showed a significantly higher level of CD80+/major
      histocompatibility complex class II double labelling (P<0.05), as compared with
      GIV (95.35+/-1.22%) and GIII (76.15+/-5.53%) mice. The expression of interferon
      gamma was significantly increased in GIV mice [5.89 (5.2-7.12)], as compared with
      GIII mice [2.75 (1.33-4.4)] (P<0.05). Similarly, the expression of IL-12 was
      markedly increased in GIV mice [1.27 (0.26-2.57)] compared with GIII mice [0.73
      (0.44-1.47)], although the difference was not significant (P=0.063). The results
      of the present study suggested that PA was able to promote the maturation of DCs
      and their secretion of anti-tumour cytokines. Therefore, PA may emerge as a tool
      in immunotherapy.

PMID- 28454270
TI  - FosB transcription factor regulates COX-2 expression in colorectal cancer cells
      without affecting PGE2 expression.
AB  - The expression levels of cyclooxygenase (COX)-2 and the prostaglandin E2 (PGE2)
      content have been associated with poor prognosis in patients with colorectal
      cancer (CRC). There is a strong correlation between COX-2 expression and PGE2
      production in tissues from CRC patients, suggesting an important role for COX-2
      on the regulation of PGE2 production. Previous studies by the present authors,
      where CRC patients were divided into high- or low-COX-2 expressing tumors,
      displayed important differences in the expression levels of several transcription
      factors involved in carcinogenesis. Among them, FBJ murine osteosarcoma viral
      oncogene homolog B (FosB), which is a member of the activator protein-1 complex,
      was the highest upregulated transcription factor in patients with high expression
      levels of COX-2. The present study aimed to investigate the role of FosB on the
      COX-2/PGE2 axis in CRC cells with high COX-2 expression levels. Interference RNA
      technology was used to knockdown FosB expression in HCA-7 cells, and 72 h later
      the messenger (m)RNA expression levels of COX-1 and COX-2, as well as the PGE2
      content, were measured. The results indicated that FosB knockdown decreased the
      expression levels of COX-2 but did not affect the PGE2 content or the mRNA
      expression levels of COX-1. The present findings suggest an important role for
      FosB on the regulation of COX-2 expression, but no effect on the regulation of
      the PGE2 levels. In addition, the present results imply independent regulatory
      mechanisms for COX-2 expression and PGE2 content.

PMID- 28454271
TI  - Intracellular and extracellular factors influencing the genotoxicity of nitric
      oxide and reactive oxygen species.
AB  - A number of factors affect cellular responses to nitric oxide (NO*) and reactive
      oxygen species (ROS), including their source, concentration, cumulative dose,
      target gene and biological milieu. This limits the extrapolation of data to in
      vivo pathological states in which NO* and ROS may be important. The present study
      investigated lethality and mutagenesis in the HPRT and TK1 genes of human
      lymphoblastoid TK6 cells exposed to NO* and ROS derived from two delivery
      methods: A reactor system and a TranswellTM co-culture. The delivery of NO* into
      the medium at controlled steady-state concentrations (given in uM/min) and the
      production of NO* and ROS by activated macrophages, resulted in a time-dependent
      decrease in total cell numbers, and an increase in mutation frequency (MF),
      compared with untreated controls. This increase in MF was effectively suppressed
      by N-methyl-L-arginine monoacetate. Single base substitutions were the most
      common type of spontaneous and NO* induced mutations in HPRT, followed by exon
      exclusions and small deletions in both delivery systems. Among the single base
      pair substitutions, an equal frequency of four types of single base substitutions
      were identified in TK6 cells exposed to NO* delivered by the reactor system,
      whereas G:C to T:A transversions and A:T to G:C transitions were more frequent in
      the co-culture system. Taken together, these results demonstrate that both the
      delivery method of NO* and ROS, and the target genes are determinants of observed
      cytotoxic and mutagenic responses, indicating that these parameters need to be
      considered in assessing the potential effects of NO* and ROS in vivo.

PMID- 28454272
TI  - Dinitrophenyl hapten with laser immunotherapy for advanced malignant melanoma: A
      clinical study.
AB  - The present study aimed to evaluate the efficacy and safety of in situ
      immunotherapy with dinitrophenyl (DNP) hapten in combination with laser therapy
      for patients with malignant melanoma (MM). Between February 2008 and March 2012,
      72 patients with stage III or IV MM were enrolled. Patients received in situ DNP
      alone (n=32) or in combination with laser therapy (n=32), and each group received
      dacarbazine chemotherapy. The levels of peripheral cluster of differentiation
      (CD)4+CD25+ regulatory T cells (Tregs), interleukin (IL)-10 and tumor growth
      factor (TGF)-beta were detected by ELISA. The association between delayed-type
      hypersensitivity (DTH) and survival time was evaluated. Although peripheral Treg
      levels significantly decreased over time in the two groups (P<0.001), there was
      no significant difference between the treatment groups (P=0.098). Patients
      receiving the combination treatment exhibited significantly higher interferon
      gamma production by CD8+ and CD4+ T cells (both P<0.001), as well as
      significantly reduced levels of IL-10, TGF-beta1 and TGF-beta2. In addition,
      patients in the combination treatment group experienced significantly longer
      overall survival (OS; P=0.024) and disease-free survival (DFS; P=0.007) times; a
      DTH response of >=15 mm was also associated with increased OS time and DFS time
      (P<=0.001). Finally, no severe adverse events were observed in either treatment
      group. Overall, in situ immunization with DNP in combination with laser
      immunotherapy may activate focal T cells, producing a regional antitumor immune
      response that increases cell-mediated immunity and improves survival in MM
      patients. Thus, this may represent a novel therapeutic strategy for patients with
      unresectable, advanced MM.

PMID- 28454273
TI  - Repurposing cimetidine for cholangiocarcinoma: Antitumor effects in vitro and in
      vivo.
AB  - Cimetidine is a histamine type-2 (H2) receptor antagonist that has been
      demonstrated to have antitumor effects on various types of malignancy. However,
      its effect on cholangiocarcinoma (CCA), a chemotherapy-resistant bile duct tumor,
      has yet to be investigated. In the present study, the antitumor activity of
      cimetidine in vitro and in vivo was evaluated. A methylthiotetrazole assay
      revealed that the proliferation of certain CCA cell lines was inhibited by
      cimetidine, which induced the caspase-dependent apoptosis of CCA cells via
      suppression of the protein kinase B signaling pathway. Suppression of Akt
      phosphorylation, caspase-3, -8 and -9 activation, phosphotidylserine exposure
      determined by Annexin V binding assay and the presence of a sub-G1 population
      were demonstrated by western blotting and flow cytometry analysis. In a CCA
      xenograft mouse model cimetidine inhibited the growth of CCA cells without
      observable adverse effects. These results suggest that cimetidine has the
      potential to be an effective antitumor agent for the treatment of CCA.

PMID- 28454274
TI  - Role of endoplasmic reticulum stress on cisplatin resistance in ovarian
      carcinoma.
AB  - Endoplasmic reticulum (ER) is an essential site of cellular homeostasis
      regulation. ER stress (ERS) may induce autophagy in tumor cells that escape from
      apoptosis. The present study examined the effects and mechanism of ERS on
      cisplatin (DDP) sensitivity in ovarian carcinoma. SKOV3 tumor cells treated with
      Saquinavir were subjected to western blot and reverse transcription-quantitative
      polymerase chain reaction analysis to determine protein and messenger RNA (mRNA)
      expression levels of mechanistic target of rapamycin (mTOR) and Beclin 1. MTT
      assay was used to analyze the influence of Saquinavir on DDP resistance in SKOV3
      cells. Saquinavir induced glucose-regulated protein 78 expression, which is a
      marker of ERS. Following treatment with various doses of Saquinavir, the
      sensitivity of ovarian cancer cells to DDP decreased significantly. Protein and
      mRNA expression levels of mTOR and Beclin 1 in SKOV3 cells were increased when
      the cells were exposed to Saquinavir or DDP for 24 h. Moreover, mTOR and Beclin 1
      expression levels were highest in the Saquinavir + DDP group (0.684+/-0.072 and
      0.6467+/-0.0468, respectively). SKOV3 tumor cells were also exposed to the
      autophagy inhibitor, 3-methyladenine (3-MA), and different concentrations of
      Saquinavir. Analysis of half maximal inhibitory concentration (IC50) values of
      DDP after this treatment demonstrated that IC50 values were significantly
      decreased compared with Saquinavir alone (P<0.001), suggesting that the
      sensitivity to DDP was improved in ovarian cancer cells after 3-MA exposure.
      These findings demonstrated that Saquinavir is able to induce ERS in SKOV3 cells
      effectively, and ER-induced stress may decrease the sensitivity of DDP in SKOV3
      cells. Furthermore, ERS may regulate cell autophagy through the mTOR and Beclin 1
      pathways, leading to a reduction in the sensitivity of DDP in SKOV3 cells. ERS in
      tumor cells and autophagy may be a potential target to improve the therapeutic
      effect of chemotherapy and reduce drug resistance in tumors.

PMID- 28454275
TI  - Variations in the multimerization region of the Helicobacter pylori cytotoxin
      CagA affect virulence.
AB  - Helicobacter pylori colonizes the human stomach by infecting gastric epithelial
      cells. It is the primary cause of peptic ulcer disease and gastric cancer (GC).
      Cytotoxin-associated gene A (CagA) is a virulence factor produced by H. pylori.
      Strains positive for the CagA protein are associated with more severe gastric
      diseases. The 3' region of the cagA gene exhibits heterogeneity with respect to
      tyrosine phosphorylation motifs (EPIYA) and CagA multimerization motifs (CM).
      CagA proteins are categorized as either Western or Eastern based on EPIYA
      sequences. CM motifs are also identified as Western and Eastern based on CM
      sequences identified in Western and East Asian countries. It has been suggested
      that CagA proteins possessing an Eastern CM type are associated with less severe
      gastric disorders. In the present study, the effects of two CagA peptides with
      different CM motifs on cell function were compared: CagA with a Western and
      Eastern CM motif (CagA-WE), and CagA with two Western CM motifs (CagA-WW). CagA
      sequences were fused with green fluorescent protein (GFP) to form GFP-CagA fusion
      proteins. GFP-CagA and GFP control constructs were transfected into human gastric
      adenocarcinoma cells (AGS). GFP-CagA expression was verified by immunoblotting
      and immunofluorescence. The results demonstrated that, following 18 h, the CagA
      WE-transfected cells were less adherent compared with the CagA-WW transfected
      cells. CagA has also been reported to cause cell elongation in AGS cells. In the
      current study, cell elongation was more frequent in the CagA-WW-transfected cells
      compared with the CagA-WE transfected cells (8.34 vs. 3.97% cells, respectively).
      The CagA peptides did not affect proliferation or apoptosis rates. These results
      suggest that different CM motif types may affect CagA virulence.

PMID- 28454276
TI  - MicroRNA-134 reverses multidrug resistance in human lung adenocarcinoma cells by
      targeting FOXM1.
AB  - Multidrug resistance (MDR) is the primary barrier to the success of chemotherapy
      for lung adenocarcinoma. MicroRNA (miR)-134, which is downregulated in lung
      adenocarcinoma, influences cell proliferation, apoptosis and invasion of lung
      adenocarcinoma. However, the function of miR-134 in the MDR of lung
      adenocarcinoma remains unclear. In the present study, it was identified that miR
      134 expression is significantly downregulated in A549/cisplatin MDR lung
      adenocarcinoma cells, as compared with A549 parental cells. miR-134 regulates the
      sensitivity of lung adenocarcinoma cells to certain anticancer drugs.
      Furthermore, it was demonstrated that forkhead box M1 and multidrug resistance
      associated protein 1 are functional targets of miR-134. These data revealed an
      important role for miR-134 in the regulation of MDR in lung adenocarcinoma.

PMID- 28454277
TI  - Monocyte-derived dendritic cells from patients with cervical intraepithelial
      lesions.
AB  - Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of
      neoplasms. However, the obtainment and protocol of differentiation of these cells
      may depend on extrinsic factors such as the tumor itself. The aim of the present
      study was to verify the influence of cervical neoplasia on different protocols of
      differentiation of monocyte-derived DCs resulting in an increased maturation
      phenotype. A total of 83 women were included in the study. The patients were
      grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade
      squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy
      patients (n=21) groups. The mononuclear cells of patients were subjected to three
      differentiation protocols. In protocol I (pI), granulocyte-macrophage colony
      stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)
      alpha were used for the differentiation of mature DCs (pIDCs). In protocol II
      (pII), monocytes were stimulated with GM-CSF, IL-4, TNF-alpha and activated
      lymphocytes in the absence of non-adherent cells (pIIDCs). In protocol III
      (pIII), monocytes were stimulated with GM-CSF, IL-4, TNF-alpha and activated
      lymphocytes in the presence of non-adherent cells (pIIIDCs). These cells were
      evaluated by flow cytometry for the expression of maturation markers such as
      cluster of differentiation (CD)11c, CD86 and human leukocyte antigen-antigen D
      related (HLA-DR). The main cytokines secreted (IL-4, IL-12 and transforming
      growth factor-beta) were measured by ELISA. Our results indicate a significantly
      lower mature profile of pIIDCs and a significant increase in CD11c+ pIIIDCs able
      to produce IL-12 (P=0.0007). Furthermore, a significant reduction in cervical
      cancer HLA-DR+ pIDCs (P=0.0113) was also observed. HSIL patients exhibited a
      higher percentage of HLA-DR+ pIIDCs (P=0.0113), while LSIL patients had a lower
      percentage of CD11c+ pIIIDCs (P=0.0411). These findings suggest that the extent
      of cervical lesions affects the process of differentiation of DCs. Furthermore,
      activated lymphocytes may induce a better maturation of monocyte-derived DCs, and
      the presence of mononuclear cells appears to contribute to the DC differentiation
      process.

PMID- 28454278
TI  - The associated pyrazolopyrimidines PP1 and PP2 inhibit protein tyrosine kinase 6
      activity and suppress breast cancer cell proliferation.
AB  - Protein tyrosine kinase (PTK)6, also known as breast tumor kinase, is a non
      receptor tyrosine kinase. It is closely associated with, but evolutionarily
      distinct from, the Src family members. PTK6 has a role in proliferation,
      migration and invasion in various cancers, and therefore has been suggested as a
      potentially valuable therapeutic target. In an attempt to develop PTK6
      inhibitors, chemicals known to inhibit various kinases were screened for their
      ability to inhibit PTK6. Pyrazolopyrimidine (PP)1, PP2 and a lymphocyte-specific
      protein tyrosine kinase inhibitor strongly inhibited the catalytic activity of
      PTK6 in vitro. These chemicals suppressed the phosphorylation of PTK6 substrate
      proteins, including signal transducer and activator of transcription 3, in human
      embryonic kidney (HEK) 293 cells expressing hyperactive PTK6. They also expressed
      selectivity towards PTK6 over other PTK members in HEK 293 cells. PP1 and PP2
      specifically inhibited the PTK6-dependent proliferation of human breast carcinoma
      T-47D cells. PP1 and PP2 were more selective for PTK6 than for Src family
      kinases, and may be useful for the treatment of PTK6-positive malignant diseases
      such as breast cancer.

PMID- 28454279
TI  - Anticancer activity of Nelumbo nucifera stamen extract in human colon cancer HCT
      116 cells in vitro.
AB  - The aim of the present study was to investigate the anticancer activities of
      Nelumbo nucifera (Ba lotus) stamen ethanol crude extract (BLSEE) in human colon
      carcinoma HCT-116 cells. MTT assay, flow cytometry analysis and reverse
      transcription-polymerase chain reaction assay were employed to investigate the
      anticancer mechanisms of BLSEE (100, 200 and 400 ug/ml) in HCT-116 cells. BLSEE
      reduced HCT-116 cell proliferation in a dose-dependent manner. BLSEE treatment
      also significantly increased the sub-G1 population in HCT-116 cells (P=0.0020 at
      400 ug/ml), as shown by flow cytometry assay. Following treatment with BLSEE, the
      mRNA levels of the apoptosis-associated factors Fas, Fas ligand, tumor necrosis
      factor-related apoptosis-inducing ligand, death receptor 4 (DR4), death receptor
      5 (DR5), caspases 3, 8 and 9, and B-cell lymphoma-2 (Bcl-2) associated X protein
      were increased, and the expression of anti-apoptotic Bcl-2 and Bcl-extra large
      was decreased in HCT-116 cells. The mRNA levels of matrix metalloproteinase (MMP)
      2, MMP-9, TIMP metallopeptidase inhibitor 1 and TIMP metallopeptidase inhibitor 2
      were also regulated by BLSEE treatment. In addition, BLSEE was able to modulate
      the expression of inflammation-associated nuclear factor-kappaB, inhibitory
      kappaBalpha, inducible nitric oxide synthase and cyclooxygenase 2 in HCT-116
      cells. The present study clearly indicated the cytotoxicity of BLSEE in HCT-116
      cells through induced cellular apoptosis. These results also suggested the BLSEE
      may be a powerful agent against colon cancer cells.

PMID- 28454280
TI  - Imaging findings of extraventricular choroid plexus papillomas: A study of 10
      cases.
AB  - Extraventricular choroid plexus papillomas (CPPs) are rare. In this study, we
      reveal the imaging findings of CPPs located in extraventricular sites. The
      imaging findings of 11 masses [10 masses on magnetic resonance imaging (MRI) and
      one mass on computed tomography (CT)] of extraventricular CPP in 10 patients were
      retrospectively observed. The mass site, size, contour, signal intensity, cystic
      or solid appearance, calcification, capsules, degree and pattern of enhancement,
      and hydrocephalus were evaluated based on CT or MRI. The misdiagnosis rate of
      CPPs in extraventricular sites was 80.0% (8/10). Solitary masses and multiple
      masses were observed in nine patients (90.0%, 9/10) and one patient (10%, 1/10),
      respectively. In addition to the typical imaging findings [a lobulated,
      cauliflower-like or mulberry-like mass that is homogeneous isointense or slightly
      hypointense on T1-weighted imaging (T1WI) and heterogeneous isointense or
      slightly hyperintense on T2WI], four masses had round or oval contours and three
      had cystic components; abnormal signal intensity (mixed hyperintense signals on
      T1WI and T2WI or slightly hyperintense signals on T1WI or hypo-/hyperintense on
      T2WI) and low or no enhancements were observed in three and six masses,
      respectively; absence of hydrocephalus and mild or local hydrocephalus were each
      observed in four subjects, respectively. Hemorrhage and psammomatous bodies
      and/or calcification were observed in four and three masses, respectively. In
      conclusion, in addition to the typical imaging findings, atypical imaging
      findings, including atypical contours, abnormal signal intensity, low enhancement
      and absence of hydrocephalus were also observed in extraventricular CPPs.

PMID- 28454281
TI  - Current status of the prognostic molecular biomarkers in breast cancer: A
      systematic review.
AB  - Biomarkers that facilitate the prediction of breast cancer prognosis can improve
      the quality of life in patients during the long period of illness and treatment.
      Particularly in recent years, with the advent of a more exhaustive analysis of
      genetic information and gene products, the molecular mechanisms at play during
      breast cancer have gradually become clearer. In the present study, a systematic
      review of the literature between 2009 and 2014 was conducted by searching for the
      keywords 'breast cancer', 'biomarkers', 'diagnosis', 'prognosis' and 'drug
      response' to clarify the present state of knowledge regarding biomarkers. In the
      final analysis, 16 studies on biomarkers for the breast cancer prognosis were
      retrieved. From these, 7 biomarkers in 9 studies were found to be strongly
      reliable predictors of prognosis and a further 7 biomarkers in 7 studies were
      poorly reliable. The use of these prognostic biomarkers should increase the
      options available for treatment algorithms.

PMID- 28454284
TI  - Anti-apoptotic protein Lifeguard does not act as a tumor marker in breast cancer.
AB  - The aim of the present study was to use an enzyme-linked immunosorbent assay
      (ELISA) to determine the concentrations of Lifeguard (LFG) protein in the serum
      of 36 patients diagnosed with breast cancer and to compare these values with the
      concentrations of LFG protein in the serum of 7 healthy volunteers in order to
      detect a possible association between the expression of LFG in the serum and the
      degree of malignancy of the disease. Although there is no direct association
      between the LFG protein concentration in the serum and the degree of malignancy
      of breast cancer, a statistically significant distribution of the concentration
      in all investigated samples was observed. This indicated an association between
      the LFG protein concentration in human serum with a currently unknown factor.

PMID- 28454282
TI  - Gastrointestinal tract cancers: Genetics, heritability and germ line mutations.
AB  - Gastrointestinal (GI) tract cancers that arise due to genetic mutations affect a
      large number of individuals worldwide. Even though many of the GI tract cancers
      arise sporadically, few of these GI tract cancers harboring a hereditary
      predisposition are now recognized and well characterized. These include Cowden
      syndrome, MUTYH-associated polyposis, hereditary pancreatic cancer, Lynch
      syndrome, Peutz-Jeghers syndrome, familial adenomatous polyposis (FAP),
      attenuated FAP, serrated polyposis syndrome, and hereditary gastric cancer.
      Molecular characterization of the genes that are involved in these syndromes was
      useful in the development of genetic testing for diagnosis and also facilitated
      understanding of the genetic basis of GI cancers. Current knowledge on the
      genetics of GI cancers with emphasis on heritability and germ line mutations
      forms the basis of the present review.

PMID- 28454283
TI  - Targeting of growth factors in the treatment of hepatocellular carcinoma: The
      potentials of polysaccharides.
AB  - Hepatocellular carcinoma (HCC) has become a leading cause of cancer-associated
      mortality worldwide and is thus of great concern. Although various
      chemotherapeutic drugs are currently used for the treatment of HCC, severe side
      effects associated with these treatments have prompted interest in novel
      therapies, including the use of certain biological macromolecules such as
      polysaccharides. Several studies have shown that polysaccharides have anticancer
      and antiproliferative effects on HCC. Vascular endothelial growth factor,
      transforming growth factor beta, epidermal growth factor and fibroblast growth
      factor may be effective targets for polysaccharides and may modulate tumor growth
      and immunity through increasing the expression levels of cytokines. The present
      review focuses on the ways in which growth factors contribute to the development
      of HCC, and on the anti-growth factor activities of natural and synthetic
      polysaccharides, as well as their effect on proinflammatory cytokines.

PMID- 28454285
TI  - Stereotactic radiosurgery for brain metastasis from gynecological malignancies.
AB  - Brain metastases are relatively uncommon in gynecological malignancies, and there
      is limited available data on their management. The present study reports the
      outcomes of patients with brain metastasis from gynecological malignancies who
      were treated with stereotactic radiosurgery (SRS). Patients with brain metastasis
      from a gynecological primary site were treated with SRS using the CyberknifeTM
      frameless SRS system. Primary lesions were treated with a single fraction of 16
      22 Gy. A total of 3 resection cavities were treated with 8 Gy 3 times, meaning a
      total of 24 Gy, and 1 recurrent lesion was re-irradiated with 5 Gy 5 times,
      meaning a total of 25 Gy. All patients were followed up with regular magnetic
      resonance imaging and clinical examinations 1 month after treatment and every 2
      months thereafter. A total of 20 lesions in 8 patients were included in this
      study; 1 patient presented with metastatic endometrial cancer and the remaining 7
      presented with metastatic ovarian cancer. The median age was 61 years (range, 48
      78 years). All patients had received systemic therapy prior to developing brain
      metastasis. A total of 3 patients underwent surgical resection and 1 patient was
      administered re-irradiation for recurrence. There were 3 local failures in 2
      patients. The actuarial 1-, 2- and 3-year local control rates were 91, 91 and
      76%, respectively. The median overall survival time was 29 months. No SRS
      associated toxicities or neurological mortalities were observed. In conclusion,
      brain metastasis from gynecological malignancies is uncommon, however, SRS is a
      safe and effective treatment modality for local control as a primary or adjuvant
      treatment in patients with this disease.

PMID- 28454286
TI  - Suspected tumor-to-meningioma metastasis: A case report.
AB  - Tumor-to-meningioma metastasis (TMM) is a fairly uncommon phenomenon. Only 7
      cases of prostate cancer with TMM have previously been described in the
      literature. The present study aimed to report a case of prostate cancer TMM, and
      to discuss the relevant clinical and neuroimaging aspects of this condition. A 68
      year-old patient presented with headaches, poor visual acuity in the left eye and
      ipsilateral eyelid droop 3 years after a Simpson II resection of a left sphenoid
      wing meningioma. Computed tomography revealed a hyperdense area suggestive of a
      recurrent left sphenoid wing meningioma. During microsurgical resection of tumor,
      the tumor presented a fibrous aspect and bled profusely. In the histological
      examination, a metastatic adenocarcinoma was identified inside the transitional
      meningioma. The immunohistochemical exam favored a prostatic primary site. The
      patient died two months later of septic shock from pneumonia. This is a rare
      metastatic presentation. The pre-operative diagnosis of TMM remains challenging
      in the majority of cases.

PMID- 28454287
TI  - Smad3 mutant mice develop colon cancer with overexpression of COX-2.
AB  - Colon cancer is the second most common cause of cancer-associated mortality in
      human populations. The aim of the present study was to identify the role of
      cyclooxygenase-2 (COX-2) in Smad3 mutant mice, which are known to develop colon
      cancer. Homozygous Smad3 (-/-) mutant mice were generated from inbred and hybrid
      Smad3 mouse strains by intercrossing the appropriate heterozygotes.
      Immunohistochemistry with COX-2 antibody was performed throughout this experiment
      and the data was validated and cross-checked with reverse transcription
      polymerase chain reaction (RT-PCR). Homozygous mutant Smad3 mice were generated
      and the overexpression pattern of COX-2 was identified by immunohistochemistry
      and validated with RT-PCR. The results of the present study demonstrated a link
      between the Smad3 mutant mice, colon cancer and COX-2. In addition, the
      overexpression pattern of COX-2 in Smad3 mutant mice that develop colon cancer
      was identified.

PMID- 28454288
TI  - Development of a novel anti-human aspartyl-(asparaginyl) beta-hydroxylase
      monoclonal antibody with diagnostic and therapeutic potential.
AB  - Human aspartyl-(asparaginyl)-beta-hydroxylase (HAAH) has recently been the
      subject of several studies, as it was previously observed to be overexpressed in
      numerous types of carcinoma cells and tissues in patient tumor samples. HAAH has
      been implicated in tumor invasion and metastasis, indicating that it may be an
      important target and biomarker for tumor diagnosis and treatment. However, the
      immunological tools currently available for the study of this protein, including
      monoclonal antibodies, are limited, as is the present knowledge regarding the
      role of HAAH in tumor therapy and diagnosis. In the present study, a recombinant
      C-terminal domain of HAAH was expressed in Pichia pastoris and a novel monoclonal
      antibody (mAb) targeting HAAH (HAAH-C) was constructed. Immunofluorescence and
      antibody-dependent cellular cytotoxicity (ADCC) assays were used to demonstrate
      the specificity and ADCC activity of this antibody. The results demonstrated that
      this anti-C-terminal HAAH mAB, in combination with an existing anti-N terminal
      HAAH mAb, exhibited a high response to native HAAH from carcinoma cell culture
      supernatant, as measured with a double antibody sandwich enzyme-linked
      immunosorbent assay. This validated novel mAB-HAAH-C may prompt further studies
      into the underlying mechanisms of HAAH, and the exploration of its potential in
      tumor diagnosis and therapy.

PMID- 28454289
TI  - Iris metastasis as the first sign of small cell lung cancer: A case report.
AB  - The current study documents an unusual case of iris metastasis as the first sign
      of small cell lung cancer (SCLC) and reviews the relevant literature to increase
      understanding and awareness of this rare condition. A 59-year-old male chronic
      smoker presented with a painful and red right eye without any disturbance of
      vision. The patient also complained of associated chronic cough and anorexia.
      Upon examination, an exfoliative, pinkish-white lesion of the right iris was
      observed. A systemic work-up was performed, which incidentally detected
      metastatic SCLC in the lower lobe of the right lung and was confirmed by
      histopathological examination. A thorough evaluation demonstrated no organ
      metastases, except in the iris. Following the failure of conservative approaches,
      the eye had to be enucleated. The clinical features, treatment and prognosis of
      this condition are briefly reviewed and the results of contrast-enhanced
      ultrasound (CEUS) examination observed in this case are presented. Despite their
      rarity, iris lesions should be considered as possible manifestations of
      underlying malignancies. Imaging techniques, particularly CEUS, may aid the
      detection, diagnosis and monitoring of such lesions.

PMID- 28454290
TI  - A multi-shRNA vector enhances the silencing efficiency of exogenous and
      endogenous genes in human cells.
AB  - RNA interference (RNAi) is a powerful technology for suppressing gene function.
      In most studies, small interfering RNAs (siRNAs) consist of one short hairpin RNA
      (shRNA) and, therefore, are often unable to achieve loss-of-function of their
      target genes. In the current study, an RNAi vector containing three shRNAs under
      the control of three RNA polymerase III U6 promoters was constructed. RNAi
      vectors containing one or two shRNAs were generated for comparisons. A pilot
      study targeting exogenously expressed DsRed in the HEK293 cell line revealed
      promising effects and a high selectivity for the multi-shRNA RNAi vector. Akt2 is
      constitutively expressed in cultured SKOV3 human ovarian cancer cells, and the
      multi-shRNA RNAi vector showed a strong efficiency for downregulating the
      expression of Akt2 in these cells, with no apparent interferon response. In
      addition, the Akt2-3shRNA vector, containing three shRNAs targeting Akt2, showed
      the best effect of all the shRNA vectors in reversing paclitaxel-induced
      resistance in SKOV3 cells. This study developed a widely applicable resource for
      enhancing the efficiency of gene silencing and a novel technique for performing
      complex loss-of-function screens in mammalian cells.

PMID- 28454291
TI  - Thioridazine has potent antitumor effects on lung cancer stem-like cells.
AB  - Thioridazine (TDZ), originally an anti-psychotic drug, suppresses several types
      of cancer and has specificity for leukemia stem cells. The present study was
      performed to assess its effect on lung cancer stem-like cells, as its effect
      remains unknown. TDZ was utilized to treat lung cancer stem-like cells (A549
      sphere cells) and its cytotoxic effect and mechanism were evaluated in vitro and
      in vivo. TDZ elicited cytotoxicity in A549 sphere cells and inhibited their
      proliferation in a dose-dependent pattern. A549 sphere cells treated with TDZ
      showed nuclear fragmentation, increased G0/G1 phase distribution, positive
      Annexin V staining, and a change in the expression of caspase family and cell
      cycle-associated proteins. These results suggest the induction of caspase
      dependent apoptosis and cell cycle arrest. In addition, TDZ treatment resulted in
      significant inhibitory effect on mice xenografts established by A549 sphere
      cells. TDZ repressed growth of lung cancer stem-like cells in vitro and in vivo,
      indicating its potential application in targeting lung cancer stem-like cells.

PMID- 28454292
TI  - DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide
      and a KDEL sequence induces a potent therapeutic antitumor effect.
AB  - Cellular immune responses play a critical role in the eradication of
      intracellular infections and malignant cells through the recognition and
      subsequent removal of the infection or malignant cells. Effective antigen
      presentation is crucial for stimulating the immune system against malignant
      cells. Calreticulin (CRT) has been used to improve antigen presentation. However,
      CRT overexpression has been previously associated with the development of
      pancreatic and breast cancer. The import and retention signals of CRT in the
      endoplasmic reticulum (ER) can be used to overcome CRT overexpression. The
      present study describes the potent antitumor effect of a DNA vaccine encoding
      human papillomavirus type 16 E6 and E7 antigens flanked by ER import and
      retention signals (SP-E6E7m-KDEL). The effect of this vaccine was compared with
      that of E6 and E7 antigens fused to human full-length CRT (hCRT-E6E7m). In the
      present study, the effectiveness of SP-E6E7m-KDEL for inducing an interferon
      gamma antigen-specific, response and its therapeutic effect against tumors was
      demonstrated, which was as effective as immunization against those antigens fused
      to CRT. This simplified strategy, using ER import and retention signal peptides
      to direct antigens to this organelle, provides an efficient alternative to
      traditional vaccines and, more importantly, a safe and potent system to induce a
      therapeutic antitumor response.

PMID- 28454293
TI  - Changes in mitochondrial function during EMT induced by TGFbeta-1 in pancreatic
      cancer.
AB  - Mitochondrial dysfunction is linked to cancer. Differences in the number,
      morphology and function of mitochondria have been observed between normal cells
      and cancer cells. However, changes in mitochondrial function during epithelial
      mesenchymal transition (EMT) in pancreatic cancer are less known. In the present
      study, the cultured human pancreatic cancer cell line Panc-1 was treated with
      transforming growth factor (TGF)beta-1. Mitochondrial functions following TGFbeta
      1 exposure in pancreatic cancer were investigated. It was noticed that TGFbeta-1
      treatment induces morphologic changes and a shift from epithelial to mesenchymal
      phenotype in pancreatic cancer. Furthermore, increased mitochondrial mass was
      detected in pancreatic cancer following TGFbeta-1 treatment. Besides, the
      production of reactive oxygen species in TGFbeta-1-treated pancreatic cancer
      cells significantly increased compared with the control cells. Our results
      indicate that the phenomenon of EMT in pancreatic cancer has an association with
      mitochondrial dysfunction. Mitochondrial dysfunction may be a cause of EMT in
      pancreatic cancer, which leads to heterogeneity in pancreatic cancer, and may be
      a potential therapeutic target in the future.

PMID- 28454294
TI  - Mesenchymal stem cell-conditioned medium promotes MDA-MB-231 cell migration and
      inhibits A549 cell migration by regulating insulin receptor and human epidermal
      growth factor receptor 3 phosphorylation.
AB  - Various in vitro and in vivo studies have linked mesenchymal stem cells (MSCs)
      with cancer, but little is known about the effect of MSCs on tumor progression.
      The present study aimed to analyze the role of the MSCs from different tissues,
      consisting of human bone marrow, adipose and the umbilical cord tissues, and the
      heterogeneity of tumors in tumor progression. By collecting the culture
      supernatants of MSCs as MSC-conditioned media (CMs), the present study found that
      MSC-CM produces no significant effect on the proliferation of MDA-MB-231 and A549
      tumor cells. The migration of MDA-MB-231 cells was enhanced upon incubation with
      MSC-CM, while that of A549 cells was inhibited. Furthermore, the phosphorylation
      of insulin receptors (IRs) was upregulated in MSC-CM-treated MDA-MB-231 cells,
      while in MSC-CM-treated A549 cells, the phosphorylation of human epidermal growth
      factor receptor 3 (Her3) was downregulated. Taken together, the findings suggest
      that the phosphorylation of IR and Her3 may contribute to the discrepant effects
      of MSC-CM on the migration of the 2 cell lines.

PMID- 28454295
TI  - NIMA-related kinase 2 regulates hepatocellular carcinoma cell growth and
      proliferation.
AB  - NIMA-related kinase 2 (Nek2) is often upregulated in human cancer and is
      important in regulating the cell cycle and gene expression, and maintaining
      centrosomal structure and function. The present study aimed to investigate the
      expression pattern, clinical significance, and biological function of Nek2 in
      hepatocellular carcinoma (HCC). mRNA and protein levels of Nek2 were examined in
      HCC and corresponding normal liver tissues. The MTT and soft agar colony
      formation assays, and flow cytometry were employed to assess the roles of Nek2 in
      cell proliferation and growth. In addition, western blot analysis was performed
      to assess the expression of cell cycle- and proliferation-related proteins. The
      results revealed that Nek2 was upregulated in HCC tissues and cell lines. The
      clinical significance of Nek2 expression was also analyzed. Inhibiting Nek2
      expression by siRNA suppressed cell proliferation, growth, and colony formation
      in hepatocellular carcinoma cell line HepG2 cells, induced cell cycle arrest in
      the G2/M phase by retarding the S-phase, and promoted apoptosis. Furthermore,
      Nek2 depletion downregulated beta-catenin expression in HepG2 cells and
      diminished expression of Myc proto-oncogene protein (c-Myc), cyclins D1, B1, and
      E and cyclin-dependent kinase 1, whilst increasing protein levels of p27. This
      demonstrates that overexpression of Nek2 is associated with the malignant
      evolution of HCC. Targeting Nek2 may inhibit HCC cell growth and proliferation
      through the regulation of beta-catenin by the Wnt/beta-catenin pathway and
      therefore may be developed as a novel therapeutic strategy to treat HCC.

PMID- 28454296
TI  - Association between BRAFV600E mutation and the clinicopathological features of
      solitary papillary thyroid microcarcinoma.
AB  - The B-Raf proto-oncogene serine/threonine kinase (BRAF)V600E mutation is an
      important oncogene in the development of papillary thyroid carcinoma (PTC) and
      has been identified as a risk factor for poor prognosis in patients with PTC.
      However, whether the BRAFV600E mutation is a prognostic marker in patients with
      solitary papillary thyroid microcarcinoma (sPTMC) has not yet been established.
      The present study aimed to identify the association between BRAFV600E mutation
      and the clinicopathological features of patients with sPTMC. A total of 108
      patients with sPTMC who underwent surgery at the Cancer Institute and Hospital of
      the Chinese Academy of Medical Sciences between December 2010 and December 2012
      were analyzed retrospectively. Exon 15 of the BRAF gene was amplified using the
      polymerase chain reaction and direct sequencing was performed to detect the
      BRAFV600E mutation. Statistical analysis was subsequently performed using SPSS
      software (version 16.0). The association between BRAFV600E mutation and
      clinicopathological features of sPTMC was tested with the chi2 test or Fisher's
      exact test, as appropriate. There were 27 males and 81 females in the cohort, who
      were aged between 22 and 66 years old, with an average age of 42 years. The
      BRAFV600E mutation was found in 59 out of 108 (54.6%) patients with sPTMC. The
      presence of the BRAFV600E mutation was demonstrated to be significantly
      associated with extrathyroidal extension (P=0.019), advanced Tumor-Node
      Metastasis stage (P=0.007) and the presence of autoimmune thyroiditis (P=0.010).
      The BRAFV600E mutation was not significantly associated with gender, anatomic
      location or subtype of sPTMC (P>0.05). In addition, the BRAFV600E mutation
      indicated poor prognosis in patients with sPTMC. These results suggest that the
      BRAFV600E mutation is a risk factor for poor prognosis in patients with sPTMC.
      This knowledge will aid in the risk stratification and post-operative management
      of patients with sPTMC.

PMID- 28454297
TI  - Association between hyperpolarization-activated channel in interstitial cells of
      Cajal and gastrointestinal dysmotility induced by malignant ascites.
AB  - Advanced malignant ascites is accompanied by gastrointestinal dysmotility, and
      patients often feel abdominal pain, abdominal distention, nausea and
      constipation. Gastrointestinal dysmotility is not only painful for the patients,
      but it reduces the absorption of nutrients and affects the physical recovery of
      patients with malignant ascites. It is reported that changes in interstitial
      cells of Cajal (ICCs) are responsible for the gastrointestinal dysmotility
      induced by malignant ascites, but the mechanism is not completely understood. The
      present study observed a significantly decreased expression of ion channels,
      including hyperpolarization-activated cyclic nucleotide-gated potassium channel 2
      (HCN2) and cyclic adenosine monophosphate, in the condition of malignant ascites.
      Using electrophysiology, it was identified that malignant ascites led to lower
      amplitude and slower frequency signals in cells of the small intestine. In
      addition, when ICCs were cultured with malignant ascites in vitro, the expression
      of HCN2 of ICCs was significantly reduced, and the data of flow cytometry
      revealed that the Ca2+ concentration of ICCs was also decreased. The results of
      electron microscopy analysis demonstrated the nuclei of ICCs were pyknotic, and
      the processes of ICCs were reduced in malignant ascites. The present study
      suggests the small intestinal dysmotility caused by malignant ascites may be
      associated with changes in HCN2 of ICCs, which offers a potential therapeutic
      target for gastrointestinal dysmotility in advanced malignant ascites.

PMID- 28454298
TI  - Expression and prognostic relevance of MAGE-A3 and MAGE-C2 in non-small cell lung
      cancer.
AB  - Melanoma-associated antigen (MAGE)-A3 and MAGE-C2 are antigens encoded by cancer
      germline genes, and have been recognized as potential prognostic biomarkers and
      attractive targets for immunotherapy in multiple types of cancer. The present
      study aimed to analyze the clinicopathological significance of MAGE-A3/C2
      expression in non-small cell lung cancer (NSCLC). The association between MAGE
      A3/C2 mRNA and protein expression, and the pathological characteristics and
      overall survival of patients with NSCLC was analyzed. In addition, the functional
      role of MAGE-A3 in human NSCLC cell line A549 was examined in vitro. MAGE-A3/C2
      mRNA expression was identified in 73% (151/206) and 53% (109/206) of patients
      with NSCLC, respectively. MAGE-A3/C2 protein expression was identified in 58%
      (44/76) and 53% (40/76) of NSCLC cases, respectively. MAGE-A3 mRNA expression was
      observed to be associated with smoking history, disease stage and lymph node
      metastasis. However, no association was identified between MAGE-C2 mRNA
      expression and the clinicopathological characteristics of patients with NSCLC.
      MAGE-A3/C2-positive patients had a poorer survival rate compared with MAGE-A3/C2
      negative patients. Multivariate analysis identified that MAGE-A3 expression may
      serve as an independent marker of poor prognosis in patients with NSCLC.
      Downregulation of MAGE-A3 mRNA expression in A549 cells resulted in lower
      migration and colony formation rates, and a higher amount of epithelial marker
      and lower amount of mesenchymal marker expression compared with the control
      group. These results indicate that MAGE-A3 serves a role in NSCLC cell metastasis
      through the induction of epithelial-mesenchymal transition. In conclusion, MAGE
      A3 may serve as a diagnostic and prognostic biomarker for patients with NSCLC,
      due to its association with tumor progression and poor clinical outcome.

PMID- 28454299
TI  - RNA interference-mediated gene silencing of cyclophilin A enhances the
      radiosensitivity of PAa human lung adenocarcinoma cells in vitro.
AB  - Radiotherapy is currently the major therapeutic strategy for patients with lung
      cancer. However, radioresistance and various side effects continue to present
      challenging issues for this form of treatment. A recent study demonstrated that
      cyclophilin A (CyPA) was overexpressed in non-small cell lung cancer and,
      therefore, presents a novel potential therapeutic target. In addition, gene
      radiotherapy is a novel method for cancer treatment. Therefore, the objective of
      the present study was to investigate the potential effect of CyPA silencing on
      radiosensitivity in human lung adenocarcinoma in vitro. The stable CyPA-silencing
      lung adenocarcinoma (PAa) cell line was generated using lentivirus-mediated small
      hairpin RNAs. The knockdown of CyPA was determined using fluorescent microscopy
      and western blot analysis. Cells were irradiated using various doses of cobalt-60
      (0, 2, 4, 6 and 8 Gy). The radiosensitizing effects were determined by a
      clonogenic survival assay. Apoptosis and cell cycle distribution were evaluated
      using flow cytometry. Silencing of CyPA significantly increased the apoptosis of
      PAa cells. In addition, the radiosensitivity of cells was markedly enhanced
      following CyPA silencing. Furthermore, silencing of CyPA, in combination with
      irradiation, induced G2/M phase cell cycle arrest. Taken together, the data
      suggest that the silencing of CyPA, combined with radiation therapy, may increase
      the therapeutic efficacy of lung cancer treatment through regulation of the cell
      cycle and apoptosis-associated signaling pathways.

PMID- 28454300
TI  - Single-cell genomic profiling of acute myeloid leukemia for clinical use: A pilot
      study.
AB  - Although bulk high-throughput genomic profiling studies have led to a significant
      increase in the understanding of cancer biology, there is increasing awareness
      that bulk profiling approaches do not completely elucidate tumor heterogeneity.
      Single-cell genomic profiling enables the distinction of tumor heterogeneity, and
      may improve clinical diagnosis through the identification and characterization of
      putative subclonal populations. In the present study, the challenges associated
      with a single-cell genomics profiling workflow for clinical diagnostics were
      investigated. Single-cell RNA-sequencing (RNA-seq) was performed on 20 cells from
      an acute myeloid leukemia bone marrow sample. Putative blasts were identified
      based on their gene expression profiles and principal component analysis was
      performed to identify outlier cells. Variant calling was performed on the single
      cell RNA-seq data. The present pilot study demonstrates a proof of concept for
      clinical single-cell genomic profiling. The recognized limitations include
      significant stochastic RNA loss and the relatively low throughput of the current
      proposed platform. Although the results of the present study are promising,
      further technological advances and protocol optimization are necessary for single
      cell genomic profiling to be clinically viable.

PMID- 28454301
TI  - Immunohistochemical profile of ING3 protein in normal and cancerous tissues.
AB  - The inhibitor of growth family, member 3 (ING3) protein may be capable of
      blocking the cell cycle via activating p53-transactivated promoters of p21 and
      Bcl2-associated X protein, and may induce apoptosis via a Fas/caspase-8-dependent
      signaling pathway. In the present study, immunohistochemistry was performed in
      order to characterize the expression profile of ING3 protein in tissue
      microarrays containing mouse and human normal tissue, human hepatocellular
      (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell
      (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196),
      colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung carcinoma
      (n=192). In mouse tissue, ING3 protein was positively detected in the cytoplasm
      of cardiomyocytes, kidney and skeletal muscle cells, and was additionally
      detected in the cytoplasm and nucleus of bronchial and alveolar epithelium,
      gastric and intestinal gland, and mammary gland cells. In human tissues, ING3
      protein was principally distributed in the cytoplasm, but was observed in the
      cytoplasm and nucleus of tongue, esophagus, stomach, intestine, lung, skin,
      appendix, bladder, cervix and breast cells. ING3 immunoreactivity was strongly
      detected in the stomach, skin and cervical tissues, whereas a weak signal was
      detected in the cerebellum, brain stem, thymus, liver, skeletal muscle, testis
      and prostate. In total, ING3-positive specimens were identified in 424 of 1,194
      tested cancer entities (35.5%). In a number of cases, ING3 expression was
      observed to be restricted to the cytoplasm and nucleus, excluding the cytoplasmic
      distribution identified in breast and hepatocellular carcinoma. Among these
      cases, ING3 was more frequently expressed in breast and gynecological types of
      cancer, including ovarian (59.2%), endometrial (47.9%), breast (38.9%) and
      cervical (35.5%) cancer. ING3-positive cases were more rare in renal clear cell
      (17.7%), hepatocellular (16.1%) and esophageal carcinoma (17.8%). It is suggested
      that ING3 may be involved in the repair and regeneration of organs or tissues,
      and may be closely associated with gynecological carcinogenesis.

PMID- 28454302
TI  - Applied analysis of ultrasound-guided ilioinguinal and iliohypogastric nerve
      blocks in the radical surgery of aged cervical cancer.
AB  - In the present study, we evaluated the effects of ultrasound-guided ilioinguinal
      and iliohypogastric nerve blocks and intratracheal general anesthesia in the
      radical surgery of aged cervical cancer. From June 2014 to December 2014, 62
      patients diagnosed with aged cervical cancer were enrolled in this study. The
      patients conformed to the indication of cervical cancer radical surgery. Patients
      were randomly divided into the test group and the control group according to the
      random number table with 31 individuals in each group. General anesthesia and
      compound ultrasound-guided ilioinguinal and iliohypogastric nerve blocks were
      applied in the test group, while intratracheal general anesthesia was used in the
      control group. The results showed that the operative time, awake time and the
      total dosage of propofol and sufentanil in the test group were significantly
      lower than those in the control group. The postoperative VAS score, the times to
      press the automatic control bump and continuous application time of the automatic
      control bump in the test group were significantly less than those in the control
      group. The occurrence rate of anesthesia-related adverse reactions in the test
      group during the perioperative period was significantly lower than that in the
      control group. Differences were statistically significant (P<0.05). We concluded
      that ultrasound-guided ilioinguinal and iliohypogastric nerve blocks
      significantly improved the analgesic effects during the perioperative and
      postoperative period in cervical cancer radical surgeries.

PMID- 28454303
TI  - Expression of ERbeta gene in breast carcinoma and the relevance in neoadjuvant
      therapy.
AB  - In the present study, we examined the expression of the estrogen receptor beta
      (ERbeta) gene in breast cancer and its relevance in neoadjuvant therapy. In
      total, 120 breast cancer patients who were hospitalized in the Departments of
      Breast Disease and Medical Oncology served as the subjects of this study. The
      subjects were diagnosed with breast cancer phase II to phase IIIA, as confirmed
      by aspiration biopsy and iconography. The patients were divided into two groups
      in a randomized control manner, with 60 patients in each group. The experimental
      group was administered the taxotere + epirubicin + cyclophosphamide (TEC) plan
      for 3-4 cycles of chemotherapy before the modified radical operation of breast
      cancer. In the control group, no TEC chemotherapy was carried out prior to
      operation. Instead, the breast lesion was removed directly by operation. After
      the operation, the IHC method was used to stain the ERbeta protein in the lesion
      tissue. The patients were classified according to whether the basement membrane
      was broken through; 5 cases had non-infiltrative carcinoma and 115 cases had
      infiltrative carcinoma. According to the pathology of the lesion, 114 cases had
      breast ductal carcinoma, 2 cases had mucinous breast carcinoma (of which there
      were 2 cases combined with ductal carcinoma), and 4 cases had breast lobular
      carcinoma. The ERbeta gene was found to be expressed in normal and breast cancer
      tissues. When ERbeta gene expression was compared before and after the
      chemotherapy, its expression was significantly increased in breast cancer
      tissues, which shows a significant statistical difference (P<0.05). In the
      experimental group, the expression of ERbeta gene in carcinoma tissue was
      significantly lower than that in the control group, and differences were
      statistically significant (P<0.05). Therefore, expression of the ERbeta gene in
      breast carcinoma tissues was high. The application of adjuvant chemotherapy
      before the modified radical operation for breast carcinoma can significantly
      lower the level of ERbeta expression. The expression levels of ERbeta gene in the
      carcinoma tissue of the patients can be treated as the evaluation index for
      neoadjuvant chemotherapy. Regarding targeted therapy and corresponding drug
      development for breast carcinoma, ERbeta can act as one of the specific drug
      targets.

PMID- 28454304
TI  - Cisplatin plus vinorelbine as induction treatment in stage IIIA non-small cell
      lung cancer.
AB  - Survival rates in patients with stage IIIA non-small cell lung cancer (NSCLC)
      remain low despite curative treatment. This is due to tumor recurrence at distant
      sites. The aim of neoadjuvant chemotherapy (NA-CT) is to eradicate occult
      micrometastatic disease and improve survival in patients that are not candidates
      for surgery following induction therapy. A total of 21 patients with ipsilateral
      mediastinal node involvement (N2) with potentially resectable disease, who had
      been diagnosed with stage IIIA (T1-3 N1-2 and T4N0) NSCLC and who had received
      cisplatin and vinorelbine as induction treatment were included in this
      retrospective study. Patients who responded to the treatment underwent surgery,
      and those who were unresponsive received radical radiotherapy. Follow-up was
      conducted between March 2008 and April 2014. The median age of patients was 61
      years, and all patients exhibited a good Eastern Cooperative Oncology Group
      performance status. The majority of patients were histologically diagnosed with
      adenocarcinoma (48%) or squamous cell carcinoma (38%), which was a poor
      prognostic factor for overall survival (OS). A total of 7 patients underwent
      surgery (of which 6 were down-staged), with a 3-year survival rate of 42.8%. The
      most significant factor associated with response to induction treatment was
      multistation nodal involvement. The complete resection rate for surgical patients
      was 85.7%. Unresectable patients had a 3-year survival rate of 25.8%. OS time for
      the whole cohort was 28.5 months, and the 3- and 5-year OS rates were 28.5% and
      4.7%, respectively. CT-induced toxicity did not affect any treatment regime or
      surgical procedures. In conclusion, the use of cisplatin plus vinorelbine is
      feasible in a neoadjuvant setting, with good response rates and acceptable
      toxicity. Multistation N2 involvement is the main prognostic factor for a poor
      response to induction treatment.

PMID- 28454306
TI  - Inhibitory effect of norcantharidin on melanoma tumor growth and vasculogenic
      mimicry by suppressing MMP-2 expression.
AB  - A form of microcirculation called vasculogenic mimicry (VM), which constitutes a
      novel approach for tumor blood supply in certain highly aggressive malignant
      tumors, was recently reported to contribute to tumor metastasis and poor
      prognosis in melanoma patients. Development of strategies to target tumor VM may
      be significant to reduce the recurrence and metastasis of melanoma.
      Norcantharidin (NCTD) has been shown to inhibit tumor growth and VM of human
      gallbladder carcinomas. Besides, NCTD could induce melanoma cell apoptosis.
      However, whether NCTD can inhibit the growth and VM formation of melanoma has not
      been evaluated. The present study aims to investigate the anti-VM activity of
      NCTD as a VM inhibitor for melanoma and its potential mechanisms. The anti-VM
      activity of NCTD was determined in human melanoma A375 cells and xenografts in
      vitro and in vivo. The findings indicate that NCTD inhibits tumor growth and VM
      formation of melanoma both in vitro and in vivo by suppressing matrix
      metalloproteinase-2 expression. The results suggest that NCTD is a potential
      therapeutic agent targeting VM in melanoma.

PMID- 28454305
TI  - MicroRNA profile of hepatic epithelioid hemangioendothelioma: A case report.
AB  - A 72-year-old female was referred for further evaluation of epigastralgia.
      Abdominal contrast computed tomography revealed numerous tumors in the two lobes
      of the liver. Liver biopsy and immunohistochemical staining revealed that the
      tumor cells were positive for factor VIII-associated antigen, platelet
      endothelial cell adhesion molecule 1 and human hematopoietic progenitor cell
      antigen, concordant with a diagnosis of hepatic epithelioid hemangioendothelioma
      (HEH). To elucidate the etiology of HEH, particularly the microRNA (miRNA)
      profiles, tissue samples obtained from normal and tumor tissues were analyzed
      using a miRNA array system. A total of 14 miRNAs were significantly upregulated
      and 93 miRNAs were downregulated in the tumor tissues (P<0.01). Additionally,
      unsupervised hierarchical clustering analysis using Pearson's correlation
      revealed that the tumor tissues clustered separately from the normal tissues. The
      miRNA expression profile was analyzed in HEH and compared with angiosarcoma,
      which exhibits histology similar to HEH. Out of a total of 107 miRNAs, only miR
      122-5p and miR-1290 demonstrated a differential expression pattern in
      angiosarcoma. Therefore, these miRNAs may be novel biological markers for the
      determination of a diagnosis of HEH in primary mesenchymal tumors of the liver.
      To the best of our knowledge, this study is the first report of a miRNA
      microarray analysis in HEH.

PMID- 28454307
TI  - miR-141 promotes colon cancer cell proliferation by inhibiting MAP2K4.
AB  - MicroRNAs (miRNAs or miRs) can function as tumor-suppressor or oncogenic genes.
      Upregulation of miRNA-141 has been frequently observed in colorectal cancer (CRC)
      samples. The experimentally observed targets of miR-141 include the tumor
      suppressor gene mitogen-activated protein kinase kinase 4 (MAP2K4). The aim of
      the present study was to investigate the role of miR-141 in the proliferation of
      colonic cancer. Western blotting, immunohistochemistry and reverse transcription
      quantitative polymerase chain reaction were used to detect the expression levels
      of miR-141 and MAP2K4 in colonic adenocarcinoma (CAC) and adjacent non-cancerous
      (NC) tissue samples, as well as in human CAC cell lines (HT29, T94 and LS174).
      MTT assay was used to investigate the proliferation and apoptosis of these three
      cell lines. The expression levels of miR-141 were significantly upregulated in
      clinical samples of CAC, compared with adjacent NC tissues. By contrast, MAP2K4
      was downregulated in CAC. The in vitro assays demonstrated that overexpression of
      miR-141 resulted in cell proliferation of CAC by inhibiting MAP2K4 activity. Our
      study suggests that targeting the miR-141-MAP2K4 signaling pathway may represent
      a novel approach for the treatment of CRC.

PMID- 28454308
TI  - Longikaurin A, a natural ent-kaurane, suppresses stemness in nasopharyngeal
      carcinoma cells.
AB  - Cancer stem cells (CSCs) are a small proportion of tumor cells that may be
      responsible for tumor metastasis and recurrence. Our recent research indicated
      that longikaurin A (LK-A) exhibited anti-tumor activity in nasopharyngeal
      carcinoma (NPC) both in vitro and in vivo. Here, we further investigated whether
      LK-A could suppress the stemness of NPC cells. Sphere formation assay was used to
      assess the self-renewal ability of the cells treated with LK-A. Side population
      (SP) was determined by flow cytometry to measure the influence of LK-A on NPC
      SPs. The expression of the c-myc and fibronectin was detected by western
      blotting. The cytotoxicity of LK-A in combination with cisplatin to NPC cells was
      determined by MTT assay. Colony formation assay was used to verify whether LK-A
      could sensitize NPC cells to radiation and reverse the radiotherapy resistance.
      In the present study, we found that LK-A reduced the number and size of spheroid
      formation and decreased the SP cell percentage of the S18 cell line at a low
      concentration. Furthermore, LK-A treatment downregulated the expression of c-myc
      and fibronectin in NPC cell lines. Moreover, LK-A could significantly enhance the
      chemotherapeutic and radiotherapeutic sensitivity of NPC cell lines and reverse
      acquired radiotherapy resistance of Sune2-IR. Our data revealed that LK-A could
      suppress the stemness of NPC cells and may enhance the efficacy of radiotherapy
      and chemotherapy.

PMID- 28454309
TI  - Targeting CD146 in combination with vorinostat for the treatment of ovarian
      cancer cells.
AB  - Drug resistance is the predominant cause of mortality in late-stage patients with
      ovarian cancer. Histone deacetylase inhibitors (HDACis) have emerged as a novel
      type of second line drug with high specificity for tumor cells, including ovarian
      cancer cells. However, HDACis usually exhibit relatively low potencies when used
      as a single agent. The majority of current clinical trials are combination
      strategies. These strategies are more empirical than mechanism-based
      applications. Previously, it was reported that the adhesion molecule cluster of
      differentiation 146 (CD146) is significantly induced in HDACi-treated tumor
      cells. The present study additionally confirmed that the induction of CD146 is a
      common phenomenon in vorinostat-treated ovarian cancer cells. AA98, an anti-CD146
      monoclonal antibody (mAb), was used to target CD146 function. Synergistic
      antitumoral effects between AA98 and vorinostat were examined in vitro and in
      vivo. The potential effect of combined AA98 and vorinostat treatment on the
      protein kinase B (Akt) pathway was determined by western blotting. The present
      study found that targeting of CD146 substantially enhanced vorinostat-induced
      killing via the suppression of activation of Akt pathways in ovarian cancer
      cells. AA98 in combination with vorinostat significantly inhibited cell
      proliferation and increased apoptosis. In vivo, AA98 synergized with vorinostat
      to inhibit tumor growth and prolong survival in ovarian cancer. These data
      suggest that an undesired induction of CD146 may serve as a protective response
      to offset the antitumor efficacy of vorinostat. By contrast, targeting CD146 in
      combination with vorinostat may be exploited as a novel strategy to more
      effectively kill ovarian cancer cells.

PMID- 28454310
TI  - Downregulation of LKB1 promotes tumor progression and predicts unfavorable
      prognosis in patients with glioma.
AB  - The liver kinase B1 (LKB1)/5'-adenosine monophosphate-activated protein kinase
      pathway has been reported to facilitate glioma cell growth by improving growth
      conditions. To investigate the clinical significance of LKB1 in human gliomas
      western blot analysis and quantitative polymerase chain reaction experiments were
      performed. The present study demonstrated that LKB1 expression was markedly
      decreased at the messenger RNA and protein levels in 30 freshly prepared glioma
      tissues, compared with non-neoplastic brain tissues (P<0.001). Subsequently,
      immunohistochemical analysis demonstrated that LKB1 immunostaining in 180 glioma
      tissues was significantly decreased compared with that in the corresponding non
      neoplastic brain tissues (P<0.001). Notably, this downregulation frequently
      occurred in high-grade gliomas, and statistical analysis revealed that low LKB1
      expression was significantly associated with large tumor size (P=0.02), advanced
      World Health Organization grade (P=0.006) and low Karnofsky performance scale
      (P=0.01). The prognostic value of LKB1 expression in patients with glioma was
      additionally evaluated using Kaplan-Meier survival curves and Cox proportional
      hazards regression models. As a result, the overall survival time of patients
      with glioma with low LKB1 expression was shorter compared with that of patients
      with high LKB1 expression (P<0.001), and low LKB1 expression also indicated
      decreased survival time in patients with high-grade glioma (P<0.001).
      Collectively, the present data indicated that the downregulation of LKB1 was
      closely associated with the malignant degree of human gliomas, exhibiting lower
      expression at a higher grade. Notably, LKB1 may serve as a potential prognostic
      biomarker for patients with glioma following surgery.

PMID- 28454311
TI  - Antitumor effects and the underlying mechanism of licochalcone A combined with 5
      fluorouracil in gastric cancer cells.
AB  - Licochalcone A (LCA) is a flavonoid extracted from licorice root that has
      antiparasitic, antibacterial and antitumor properties. Previous studies have
      revealed that LCA may be a novel treatment for gastric cancer. The present study
      further assessed the potential antitumor effects of LCA alone or in combination
      with 5-fluorouracil (5-FU), and the underlying mechanisms responsible for those
      effects in gastric cancer cells. The effects of LCA alone or in combination with
      5-FU on SGC7901 and MKN-45 gastric cancer cell lines were studied using Cell
      Counting Kit-8, cell cycle, apoptosis and western blot analyses of cell check
      points and apoptosis-associated proteins. The results revealed that LCA inhibited
      cell proliferation, blocked cell cycle progression at the G2/M transition and
      induced apoptosis. Western blot analysis demonstrated that LCA treatment
      increased the levels of tumor proteins 21 and 27, as well as mouse double minute
      2 homolog in gastric cancer cells. In addition, LCA treatment increased the
      expression levels of Bax, cleaved-poly ADP ribose polymerase, tumor protein 53
      and caspase 3, and decreased the expression levels of Bcl-2. Therefore, the
      present study demonstrated that LCA alone or in combination with 5-FU may have
      significant anticancer effects on gastric cancer cells, and may be a novel
      therapeutic for the treatment of gastric cancer in the future.

PMID- 28454312
TI  - Treatment with a selenium-platinum compound induced T-cell acute lymphoblastic
      leukemia/lymphoma cells apoptosis through the mitochondrial signaling pathway.
AB  - T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive
      hematological disorder that is sensitive to chemotherapy; however, it exhibits
      frequent relapse rates. Platinum-containing therapeutics are the first-line
      salvage regimens used in the treatment of relapsed or refractory T-ALL/LBL. The
      selenium-platinum compound EG-Se/Pt is obtained from the combination of selenium
      containing molecules (EG-Se) with cisplatin (CDDP); however, its anticancer
      properties have been poorly investigated. In the present study, the Cell Counting
      Kit-8 assay was used to evaluate the inhibitory effect of treatment with EG-Se/Pt
      on cell viability. Cell cycle distribution, apoptosis, reactive oxygen species
      (ROS) content and the mitochondrial membrane potential were analyzed using flow
      cytometry. Intracellular platinum content was detected using inductively coupled
      plasma mass spectrometry. Caspase activity was determined using a colorimetric
      assay. The expression of several proteins associated with apoptosis was analyzed
      using western blotting. The results of the present study demonstrated that
      treatment with EG-Se/Pt increased the inhibition of Jurkat and Molt-4 T-ALL/LBL
      cell viability compared with CDDP, and induced apoptosis and cell cycle arrest.
      The intracellular platinum content of T-ALL/LBL cells treated with EG-Se/Pt was
      increased compared with that of T-ALL/LBL cells treated with CDDP. EG-Se/Pt
      induced apoptosis was mediated by caspase and ROS levels through the activation
      of the mitochondrial signaling pathway. The results of the present study suggest
      that EG-Se/Pt is a potential therapeutic candidate for the treatment of T
      ALL/LBL.

PMID- 28454313
TI  - A novel t(9;22;11) translocation involving 11q24 in a patient with chronic
      myeloid leukemia: A case report.
AB  - Variant Philadelphia chromosome translocations involving chromosomes other than 9
      and 22 have been reported in 5-10% of patients with chronic myeloid leukemia
      (CML). As part of the three-way variant t(9;22;11) in patients with CML, 11q24 is
      a novel region that has not previously been investigated. A 22-year-old male
      exhibiting chronic phase CML developed a recurrence of the same phase subsequent
      to the interruption of imatinib treatment and showed the same chromosomal
      abnormality, t(9;22;11)(q34;q11.2;q24), that was detected at the initial
      diagnosis. The recurrent CML responded well to imatinib therapy. These findings
      suggest that the three-way variant, t(9;22;11), involving 11q24 may be associated
      with a good prognosis and response to imatinib. This is the first report of three
      way variant involving 11q24 in a patient with CML.

PMID- 28454314
TI  - Synchronous and bilateral oncocytic carcinoma of the breast: A case report and
      review of the literature.
AB  - Synchronous bilateral breast cancer is rare, and oncocytic carcinoma is an even
      rarer breast cancer histological subtype. In general, oncocytic tumors are
      defined as neoplasms with eosinophilic granular cytoplasm and have been reported
      in various organs. Oncocytic carcinoma of the breast was first documented by
      Gadaleanu and Craciun in 1987, and 48 cases have since been reported. The present
      study reports a case of synchronous bilateral breast oncocytic carcinoma. The
      patient was a 78-year-old woman. Although she exhibited no symptoms, chest
      computed tomography revealed three multinodular breast tumors: Two in the right
      breast and one in the left. Core needle biopsy was performed on the three tumors,
      and the patient was diagnosed with invasive ductal carcinoma with potential
      apocrine carcinoma. A bilateral modified radical mastectomy was performed.
      Surgical specimens of the three tumors revealed cord- or nest-forming tumor cells
      with eosinophilic granular cytoplasm. Immunohistochemically, the tumor cells were
      markedly positive for mitochondria. Electron microscopy of the tumor samples
      additionally revealed numerous mitochondria filling the cytoplasm. Based on these
      findings, the tumors were diagnosed as oncocytic carcinoma. The pathogenesis of
      oncocytic carcinoma remains to be fully elucidated; thus, additional
      clinicopathological studies are required.

PMID- 28454315
TI  - Correlation between the efficacy of amrubicin and the previous chemotherapy
      regimen for relapsed small cell lung cancer.
AB  - Amrubicin has been demonstrated to be beneficial in the treatment of patients
      with relapsed small cell lung cancer (SCLC). The aim of the present study was to
      evaluate whether there is a significant difference in the efficacy of amrubicin
      between patients with relapsed SCLC who were previously treated with a platinum
      agent in combination with a topoisomerase I inhibitor, and those patients
      previously treated with a platinum agent in combination with a topoisomerase II
      inhibitor. The medical records of patients with SCLC, who were diagnosed as
      having relapsed following treatment with a platinum-based regimen and
      subsequently received amrubicin monotherapy, were retrospectively reviewed. Of a
      total of 48 patients with SCLC who were treated with amrubicin, the overall
      response rate, median progression-free survival (PFS) time and median survival
      time (MST) were determined to be 31.3%, 7.1 and 17.0 months, respectively. The
      response rate, PFS time and MST did not differ significantly between the patients
      treated previously with a platinum agent in combination with irinotecan, a
      topoisomerase I inhibitor, (36.4%, 5.7 and 11.4 months, respectively) and those
      treated previously with a platinum agent in combination with etoposide, a
      topoisomerase II inhibitor (30.0%, 4.7 and 14.8 months, respectively). The
      results indicate that amrubicin may be effective as a second-line
      chemotherapeutic agent for patients with SCLC, irrespective of which platinum
      agent and topoisomerase inhibitor-based chemotherapy regimen was previously
      administered.

PMID- 28454316
TI  - Overexpression of N-cadherin and beta-catenin correlates with poor prognosis in
      patients with nasopharyngeal carcinoma.
AB  - An increasing amount of evidence demonstrates that epithelial-mesenchymal
      transition (EMT) is important in tumor invasion and metastases. The cell-cell
      adhesion molecule N-cadherin and the Wnt/beta-catenin cascade protein beta
      catenin are two biomarkers of EMT. The present study aimed to measure the
      expression levels of N-cadherin and beta-catenin in samples from patients with
      nasopharyngeal carcinoma (NPC) and evaluate their prognostic significance. N
      cadherin and beta-catenin mRNA was evaluated using reverse transcription
      quantitative polymerase chain reaction in 26 NPC tissue samples and 8
      nasopharyngeal epithelium samples. Protein expression of N-cadherin and beta
      catenin was also detected using immunohistochemistry in 128 archival NPC paraffin
      embedded specimens. Finally, associations between clinical pathological
      parameters and prognostic values in NPC were evaluated. The results demonstrated
      that both the mRNA and protein levels of N-cadherin and beta-catenin were
      significantly increased in NPC tissues compared with the controls. Enhanced
      expression of N-cadherin and beta-catenin protein was strongly correlated with
      the status of lymph node metastasis and clinical stages in patients with NPC.
      Notably, high expression of N-cadherin and beta-catenin proteins was
      significantly correlated with lower overall survival (OS) rate in patients with
      NPC. Finally, multivariate analysis demonstrated that expression of N-cadherin
      protein and clinical stages were independent prognostic factors for patients with
      NPC. Therefore, the present study demonstrated that N-cadherin and beta-catenin
      expression may be used as potential prognostic biomarkers for patients with NPC.

PMID- 28454317
TI  - Usefulness of miRNA profiles for predicting pathological responses to neoadjuvant
      chemotherapy in patients with human epidermal growth factor receptor 2-positive
      breast cancer.
AB  - Pathological complete response (pCR) is considered to be a useful prognostic
      marker for neoadjuvant chemotherapy to improve the survival rate of patients with
      operable breast cancer. In the present study, we identified differentially
      expressed microRNAs (miRNAs) between pCR and non-pCR groups of patients with
      human epidermal growth factor receptor 2 (HER2)-positive breast cancer who
      received neoadjuvant chemotherapy with trastuzumab. Expression profiles were
      examined by miRNA microarrays using total RNA extracted from formalin-fixed,
      paraffin-embedded tissues from pretreatment biopsy specimens. Significant
      differences were observed in miRNAs associated with pCR between the luminal B
      like (HER2-positive) and HER2-positive (nonluminal) subtypes, which were further
      classified according to their estrogen receptor (ER) status. Prediction models
      constructed with differentially expressed miRNAs performed well. In conclusion,
      the combination of miRNA profiles and ER status may improve the accuracy of pCR
      prediction in patients with HER2-positive breast cancer and enable the
      development of personalized treatment regimens.

PMID- 28454318
TI  - Expression and prognostic value of matriptase in ovarian serous adenocarcinoma.
AB  - Previous studies have demonstrated that matriptase is involved in degradation of
      the extracellular matrix and angiogenesis, and is overexpressed in certain forms
      of epithelial cancer. The present study aimed to examine matriptase expression in
      ovarian serous adenocarcinoma, and to investigate its association with
      clinicopathological characteristics and patient prognosis. Matriptase expression
      was analyzed in 80 ovarian serous adenocarcinoma and 12 normal ovarian tissue
      samples by immunohistochemistry. All data were analyzed to evaluate the
      association between matriptase expression and clinicopathological parameters and
      overall survival. Immunohistochemistry demonstrated that matriptase protein was
      significantly overexpressed in the ovarian serous adenocarcinoma tissues compared
      with the normal ovarian tissues (P=0.0003). Furthermore, matriptase expression
      was significantly associated with clinical stage (P=0.0077) and lymph node
      metastasis (P=0.0111). Kaplan-Meier survival curves demonstrated that patients
      with positive matriptase expression had significantly greater survival times
      (P=0.0008). Matriptase expression is associated with early stage and a greater
      survival time; therefore, this protein may function as a novel diagnostic and
      prognostic marker.

PMID- 28454319
TI  - Construction and expression of a lentivirus expression vector carrying the
      VEGF165-EGFP fusion gene in breast cancer MCF-7 cells.
AB  - Vascular endothelial growth factor (VEGF)165 is one of the most abundant and
      potent angiogenic factors in both physiological and pathological conditions.
      However, the function and mechanism of VEGF165 in tumors and their environment
      remain to be elucidated. In the present study, a lentivirus vector (LV) that
      contained the VEGF165-enhanced green fluorescent protein (EGFP) fusion gene was
      constructed and transfected into the human breast cancer cell line MCF-7.
      Following transfection, the expression of VEGF165 in MCF-7 cells was detected by
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and
      western blotting. Further cellular localization of VEGF165 was observed through
      fluorescence microscopy. The titer of the recombinant lentivirus was 5.44*107
      TU/ml in the LV-VEGF165-EGFP group and 5.00*108 TU/ml in the LV-EGFP negative
      control group. RT-qPCR and western blotting demonstrated that the expression of
      VEGF165 was significantly increased in the LV-VEGF165-EGFP group compared with
      the control group. The present study lays the foundation for in vitro and in vivo
      studies on tumor cell derived-VEGF165. Furthermore, the present fusion gene
      expression vector may provide a potential approach for gene therapy treatment of
      cancer and other diseases that require regulation of angiogenesis.

PMID- 28454320
TI  - miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain
      containing protein 1.
AB  - The molecular mechanisms underlying the dysregulation of microRNAs (miRs) have
      been previously documented in breast cancer. miR-198 has been reported to be
      deregulated in several human cancers. However, the detailed effects of miR-198 on
      breast cancer progression remain unclear. Using quantitative polymerase chain
      reaction analysis, we demonstrated in the present study that miR-198 was
      downregulated in breast cancer tissues and cell lines, and that downregulation of
      miR-198 was significantly correlated with lymph node metastasis. Functional
      studies revealed that miR-198 inhibited cell proliferation and migration and
      promoted cell adhesion in aggressive breast cancer cells in vitro. In addition,
      we observed that CUB domain-containing protein 1 (CDCP1) was a direct target of
      miR-198, and that knockdown of CDCP1 inhibited cell proliferation and migration,
      and promoted cell adhesion, which was similar to the effects of overexpression of
      miR-198. Taken together, we provide evidence to characterize the role of miR
      198/CDCP1 interaction in breast cancer, which may be useful in breast cancer
      therapy.

PMID- 28454321
TI  - The loss of CASP4 expression is associated with poor prognosis in esophageal
      squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) has high biological malignant potential
      among the various digestive tract cancers and is associated with a poor
      prognosis. To identify novel genes involved in tumor progression, the present
      study analyzed the genetic and transcriptional alterations in two clinical
      cohorts, totaling 157 cases of ESCC (78 cases from the discovery set and 79 cases
      from the validation set). From the discovery set, gene expression and copy number
      profiles were analyzed using expression arrays and array-comparative genomic
      hybridization, respectively. Notably, a copy number loss of caspase-4 (CASP4) was
      observed in 82% of ESCC cases and CASP4 expression levels were significantly
      associated with copy number levels. Gene set enrichment analysis demonstrated
      that the upregulation of CASP4 expression levels was associated with the
      signaling pathways involved in apoptosis, inflammatory responses and immune
      responses. The present study demonstrated that CASP4 expression levels were
      significantly associated with the expression levels of the endoplasmic reticulum
      (ER) stress marker glucose-regulated protein 78, indicating that CASP4 has a role
      in cell death induced by ER stress in ESCC. In the survival analysis the CASP4
      low expression group exhibited a poor prognosis, compared with the CASP4 high
      expression group in the discovery set (P=0.003); this observation was reproduced
      in the validation set (P=0.037). Therefore, the results of the current study
      suggest that CASP4 may function as a tumor-suppressor gene and may have
      applications as a biomarker for the prediction of the prognosis in ESCC.

PMID- 28454322
TI  - Accumulation of low-dose BIX01294 promotes metastatic potential of U251
      glioblastoma cells.
AB  - BIX01294 (Bix) is known to be a euchromatic histone-lysine N-methyltransferase 2
      inhibitor and treatment with Bix suppresses cancer cell survival and
      proliferation. In the present study, it was observed that sequential treatment
      with low-dose Bix notably increases glioblastoma cell migration and metastasis.
      It was demonstrated that U251 cells sequentially treated with low-dose Bix
      exhibited induced characteristic changes in critical epithelial-mesenchymal
      transition (EMT) markers, including E-cadherin, N-cadherin, beta-catenin and zinc
      finger protein SNAI2. Notably, sequential treatment with Bix also increased the
      expression of cancer stem cell-associated markers, including sex determining
      region Y-box 2, octamer-binding transcription factor 4 and cluster of
      differentiation 133. Neurosphere formation was significantly enhanced in cells
      sequentially treated with Bix, compared with control cells (control: P=0.011;
      single treatment of Bix, P=0.045). The results of the present study suggest that
      accumulation of low-dose Bix enhanced the migration and metastatic potential of
      glioblastoma cells by regulating EMT-associated gene expression, which may be the
      cause of the altered properties of glioblastoma stem cells.

PMID- 28454323
TI  - MicroRNA-29a/b/c targets iNOS and is involved in protective remote ischemic
      preconditioning in an ischemia-reperfusion rat model of non-alcoholic fatty liver
      disease.
AB  - Remote ischemic preconditioning (RIPC) protects against the injury that is
      incurred by ischemia and reperfusion (IR); however, the role of RIPC in liver IR
      injury in non-alcoholic fatty liver disease (NAFLD) remains unclear. In this
      study, a NAFLD rat model was utilized in a series of different surgical
      procedures and molecular experiments. Rats of the IR group and the RIPC+IR group
      exhibited more severe injury than NAFLD control rats (in which the liver was
      prodded following a median-incision laparotomy). The liver condition, measured by
      serum alanine transaminase and aspartate transaminase levels, of the RIPC+IR
      group was better than that of the IR group. In addition, alanine transaminase and
      aspartate transaminase levels were lower in the RIPC+IR group compared with the
      IR group (P<0.001). Flow cytometry revealed that the cell apoptosis ratio was
      significantly lower in the RIPC+IR group than in the IR group (P<0.001). Reverse
      transcription-polymerase chain reaction (RT-qPCR) was used to assess miR-29a/b/c
      levels, revealing that they were significantly reduced in the RIPC and RIPC+IR
      groups, but did not vary in the IR group compared with the control group. RT-qPCR
      also revealed that iNOS mRNA levels were not significantly different among any of
      the NAFLD groups; however, western blot analysis indicated that iNOS protein
      levels were increased in the RIPC group and the RIPC+IR group compared with the
      control and IR groups. A luciferase reporter assay demonstrated that transfection
      with miR-29a/b/c mimics significantly decreased the luciferase activities of
      plasmids containing the wild-type iNOS 3'-untranslated region (UTR) (relative
      fluorescence intensity: 0.47+/-0.06 for miR-29a, 0.36+/-0.07 for miR-29b, 0.41+/
      0.04 for miR-29c; P<0.001), whereas the activities of plasmids containing the
      mutant iNOS 3'-UTR sequence were not markedly affected [relative fluorescence
      intensity: 0.99+/-0.08 for miR-29a (P=0.1349), 0.99+/-0.09 for miR-29b
      (P=0.1607), 0.97+/-0.07 for miR-29c (P=0.1824)]. This suggested that miR-29a/b/c
      downregulates iNOS by directly targeting its 3'-UTR. In summary, the results
      suggest that RIPC has a protective effect in NAFLD liver IR injury, which may be
      due to reduced miR-29a/b/c levels in the skeletal muscle, leading to increased
      iNOS and, therefore, nitric oxide.

PMID- 28454324
TI  - Stathmin 1 promotes the proliferation and malignant transformation of pancreatic
      intraductal papillary mucinous neoplasms.
AB  - Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are a type of
      pancreatic tumor, which have been identified following improvements in diagnostic
      imaging. However, the malignant transformation of IPMN has been difficult to
      diagnose clinically. To date, the mechanisms driving the progression of IPMN to
      cancer remain to be fully elucidated. The present study focused on Stathmin 1
      (STMN1), a protein that is associated with the development of various types of
      cancer. The expression of STMN1 was examined immunohistochemically in tissues
      from cases of IPMN. The correlation between the STMN1 staining and clinical
      pathological factors was evaluated, and the expression of STMN1, p27 and S-phase
      kinase-associated protein 2 (SKP2) were compared. High expression levels of STMN1
      were significantly correlated with regions of malignancy, and was associated with
      high expression of SKP2, low expression of nuclear p27 and a high Ki-67 index.
      High expression levels of STMN1 and SKP2 were significantly correlated with the
      transformation of IPMN to carcinoma. In addition, within the regions of
      carcinoma, the expression of STMN1 was weak in regions of adenoma and high in the
      cancerous regions. It was concluded that the high expression of STMN1 contributed
      to tumor proliferation and malignant transformation in the patients with IPMN.
      These results suggested that characterization of the expression of STMN1 may be a
      promising approach for predicting malignant transformation of pancreatic
      intraductal papillary mucinous adenoma.

PMID- 28454325
TI  - miR-600 inhibits cell proliferation, migration and invasion by targeting p53 in
      mutant p53-expressing human colorectal cancer cell lines.
AB  - Mutations of the tumor protein p53 gene, a tumor suppressor, are one of the most
      frequent genetic alterations observed in cancer. It has been reported that
      mutations in p53 result in the loss of wild-type p53 activity, and the gain of
      novel oncogenic properties that promote tumor growth and progression. Recent
      studies have demonstrated that a number of microRNAs (miRs) are involved in the
      post-transcriptional regulation of p53. The present study demonstrates that miR
      600 is a direct negative regulator of p53 through binding a site in the 3'
      untranslated region of p53 mRNA in human colorectal cancer (CRC) cells.
      Overexpression of miR-600 by lentiviral-mediated transduction decreased
      endogenous levels of p53 protein and inhibited cell proliferation, migration and
      invasion in mutant p53-expressing human CRC cell lines (SW480, SW620 and DLD-1)
      in vitro. In addition, silencing of p53 with small interfering RNA led to a
      similar phenotype. Furthermore, overexpression of miR-600 or p53 knockdown
      suppressed the expression of matrix metalloproteinase 9, and promoted the
      expression of E-cadherin and beta-catenin. The results of the current study
      demonstrate that miR-600 is an important negative regulator of p53, and suggest
      that targeting mutant p53 using lentiviral-mediated miR-600 overexpression is a
      promising therapeutic strategy for the treatment of CRCs with p53 mutations.

PMID- 28454326
TI  - TRIM24 promotes the aggression of gastric cancer via the Wnt/beta-catenin
      signaling pathway.
AB  - Tripartite motif-containing 24 (TRIM24) is important in tumor development and
      progression. However, the role of TRIM24 in gastric cancer (GC) and the
      mechanisms underlying the dysregulated expression of TRIM24 remain to be fully
      elucidated. In the present study, it was found that TRIM24 was frequently
      overexpressed in GC cell lines and tissues compared with normal controls, as
      determined by western blotting and immunohistochemical staining. The high nuclear
      expression of TRIM24 was correlated with the depth of invasion (P=0.007), tumor
      node-metastasis stage (P=0.005), and lymph node metastasis (P=0.027), and shorter
      overall survival rates (P=0.010) in patients with GC. Small interfering RNA
      mediated knockdown of TRIM24 inhibited cell proliferation, colony formation,
      migration, invasion and the nuclear accumulation of beta-catenin, and it delayed
      cell cycle progression and induced apoptosis. In addition, the expression of
      TRIM24 was positively correlated with that of beta-catenin in GC tissues. TRIM24
      knockdown decreased the expression of Wnt/beta-catenin target genes, whereas the
      activation of Wnt/beta-catenin signaling by lithium chloride reversed the effects
      of TRIM24 knockdown. Taken together, these data suggested that TRIM24 was a
      prognostic or potential therapeutic target for patients with GC and was important
      in the activation of the Wnt/beta-catenin pathway during the progression of GC.

PMID- 28454327
TI  - Stereotactic radiotherapy in the treatment of local recurrences of esophageal
      cancer.
AB  - Esophageal cancer (EC) consists of tumors with a generally poor prognosis, and
      treatment options for patients with disease recurrence are extremely limited. Due
      to this poor patient prognosis, the possible treatment toxicity should be
      carefully balanced against its potential benefit and patient quality of life.
      Stereotactic body radiotherapy (SBRT) is a rapidly expanding novel technique
      combining a short treatment time together with high local efficacy and an
      acceptable toxicity profile. There are no publications thus far presenting data
      regarding the usage of SBRT utilizing a conventional linear accelerator in
      locally recurrent EC patients. In the present study, 2 patients with recurrent EC
      in the neck lymph nodes were treated by SBRT in the Department of Oncology,
      University Hospital Olomouc, Czech Republic. The treatment dose was 30 and 40 Gy
      in 5 daily fractions, with a prescribed dose to 65 and 81% isodose, for each
      patient respectively, utilizing a volumetric arc therapy technique, a 6-MV photon
      beam and an Elekta Synergy linear accelerator. The treatment was delivered
      without any unintentional treatment interruptions and without any treatment
      related acute toxicity. The maximum dose in the patients was 45.9 and 49.2 Gy,
      respectively. The maximum doses for the surrounding major blood vessels were 35.4
      and 45.7 Gy, respectively. Maximum doses to the trachea and the esophagus in the
      first patient were 32.6 and 27.0 Gy. In the second patient, these doses were not
      clinically significant. SBRT utilizing linear accelerators should be considered
      in patients with localized recurrent EC, offering the patients the chance for
      local control with minimal treatment toxicity.

PMID- 28454328
TI  - Reconstruction of mandibular defects with autogenous bone and decellularized
      bovine bone grafts with freeze-dried bone marrow stem cell paracrine factors.
AB  - The gold standard following segmental mandibulectomy is vascularized autologous
      bone graft in the form of the fibula flap. However, in bone reconstruction the
      use of autogenous bone does not always guarantee a successful outcome. The aim of
      the present investigation was to develop a novel biologically active bone (BAB)
      graft, and to use it for the reconstruction of large size defects of the mandible
      bone following tumor resection. In the first part of the present study,
      biologically active bone graft was developed by using human freeze-dried bone
      marrow stem cells (BMSCs) paracrine factors and three-dimensional bone scaffold
      derived from cancellous bovine bone following decellularization. In the second
      part of the research, one male and three female patients with primary tumors of
      the mandible underwent hemimandibulectomy. The mandibular bone defects following
      tumor resection were reconstructed with autogenous rib grafts in three patients
      and BAB graft was used in one patient. The graft-host interfaces were covered
      with decellularized human amnion/chorion membrane graft. All patients were
      followed-up every five months following the reconstruction of the mandible, with
      no complications observed. Preliminary clinical investigations demonstrated that
      a BAB graft containing freeze-dried BMSC paracrine factors may be used for the
      reconstruction of large mandibular bone defects following tumor resection.

PMID- 28454329
TI  - Overexpression of heat-shock factor 1 is associated with a poor prognosis in
      esophageal squamous cell carcinoma.
AB  - Heat-shock factor 1 (HSF1) is the primary regulator of the response to various
      stressors. A previous study showed that HSF1 expression is associated with a poor
      prognosis in breast cancer and hepatocellular carcinoma; however, the prognostic
      significance of HSF1 in esophageal squamous cell carcinoma (ESCC) is unknown.
      Therefore, the present study investigated the association between HSF1 expression
      and the clinicopathological parameters of patients, as well as the association
      between HSF1 expression, and heat shock protein (Hsp)27, Hsp70 and Hsp90
      expression induced by HSF1, by cDNA microarray and immunohistochemistry analyses.
      HSF1 protein and mRNA expression were assessed in resected specimens from 270
      patients with ESCC in two independent cohorts. Hsp27, Hsp70 and Hsp90 expression
      were also assessed in 55/270 patients. Patients with high HSF1 expression had a
      significantly worse OS than those with low HSF1 expression in both cohorts. In
      multivariate analyses, pathological T stage [hazard ratio (HR), 2.21; 95%
      confidence interval (CI), 1.38-3.65; P=0.0008], pathological N stage (HR, 1.73;
      95% CI, 1.04-3.02; P=0.03) and HSF1 expression (HR, 2.29; 95% CI, 1.48-3.64;
      P=0.0002) were statistically significant independent prognostic factors.
      Furthermore, Hsp27 and Hsp90 expression were significantly correlated with HSF1
      expression (P<0.0001), but Hsp70 expression was not (P=0.38). These results
      indicate that HSF1 is a prognostic factor for patients with ESCC, and that Hsp27
      and Hsp90, but not Hsp70, may be the downstream targets of HSF1 in ESCC.

PMID- 28454330
TI  - High BIM mRNA levels are associated with longer survival in advanced gastric
      cancer.
AB  - Chemotherapy drugs, including 5-fluorouracil (5-FU), oxaliplatin and docetaxel,
      are commonly used in the treatment of gastric cancer (GC). Apoptosis-relevant
      genes may be associated with drug resistance. In the present study, the messenger
      RNA (mRNA) expression levels of B-cell lymphoma 2 interacting mediator of cell
      death (BIM), astrocyte elevated gene-1 (AEG-1) and AXL receptor tyrosine kinase
      (AXL) were investigated in 131 advanced GC samples, and the expression levels of
      these genes were correlated with patients' overall survival (OS). All 131
      patients received first-line FOLFOX combination chemotherapy with folinic acid
      and 5-FU, in which 56 patients were further treated with second-line docetaxel
      based chemotherapy. A correlation between the mRNA expression levels of BIM and
      AEG-1 was observed (rs=0.30; P=0.002). There was no association between the mRNA
      expression levels of any of the individual genes analyzed and OS in patients only
      receiving first-line FOLFOX chemotherapy. In a subgroup of patients receiving
      docetaxel-based second-line chemotherapy, those with high or intermediate levels
      of BIM exhibited a median OS of 18.2 months [95% confidence interval (CI), 12.8
      23.6], compared with 9.6 months (95% CI, 8.9-10.3) in patients with low BIM
      levels (P=0.008). However, there was no correlation between the mRNA expression
      levels of AEG-1 or AXL and OS. The risk of mortality was higher in patients with
      low BIM mRNA levels than in those with high or intermediate BIM mRNA levels
      (hazard ratio, 2.61; 95% CI, 1.21-5.62; P=0.010). Therefore, BIM may be
      considered as a biomarker to identify whether patients could benefit from
      docetaxel-based second-line chemotherapy in GC.

PMID- 28454331
TI  - Centrosome amplification in chondrosarcomas: A primary cell culture and
      cryopreserved tumor sample study.
AB  - The genetics background underlying the aggressiveness of chondrosarcoma (CS) is
      poorly understood. One possible cause of malignant transformation is chromosomal
      instability, which involves an error in mitotic segregation due to numerical
      and/or functional abnormalities of centrosomes. The present study aimed to
      evaluate centrosome amplification in cryopreserved samples of tumor tissue from
      patients with CS. An analysis was performed on 3 primary cultures of tumors from
      patients who underwent surgery between January 2012 and December 2012 at the
      Department of Orthopedics at the Barretos Cancer Hospital (Barretos, Brazil).
      Additionally, cryopreserved tumor specimens were analyzed from 10 patients. The
      data were assessed using immunocytochemistry and immunohistochemistry staining
      techniques with monoclonal antibody anti-gamma-tubulin. A total of 4 samples of
      CS cultured cells were obtained from 3 patients. A recurrence of a histological
      grade III tumor was detected in a female patient with Ollier's syndrome. The
      other 2 cases were grade I and III. The incidence of centrosome amplification in
      the primary cultures ranged from 15-64% of the cells. Whereas control cultured
      fibroblasts showed baseline levels of 4% amplified cells. For the cryopreserved
      specimens, two independent observers analyzed each sample and counted the cells
      stained with gamma-tubulin, verifying the percentage of affected cells to be a
      mean of 14%, with the number of clusters ranging between 0-6 per slide. In
      conclusion, centrosome amplification was found to be a consistent biological
      feature of CS and may underlie chromosomal instability in this tumor.

PMID- 28454332
TI  - Zoledronic acid reverses cisplatin resistance in nasopharyngeal carcinoma cells
      by activating the mitochondrial apoptotic pathway.
AB  - Despite improvements to radiotherapeutic strategies, resistance to adjuvant
      chemotherapy remains the main problem underlying the low 5-year survival rate in
      patients with nasopharyngeal carcinoma (NPC). In the present study, the human NPC
      cell line HNE1 was exposed to gradually increasing concentrations of cisplatin
      (CDDP) in order to establish a drug-resistant sub-cell line, HNE1/CDDP. HNE1/CDDP
      cells exhibited multidrug resistance and a prolonged doubling time, as compared
      with the parent HNE1 cells. Furthermore, pretreatment with zoledronic acid (ZOL)
      appeared to resensitize the CDDP-resistant cells by inducing S-phase cell cycle
      arrest and the mitochondrial apoptotic pathway by upregulating the expression of
      B-cell lymphoma-2 (BCL-2)-associated X protein and caspase-9 and downregulating
      the expression of BCL-2. The results of the present study suggested that
      HNE1/CDDP cells are a stable, multidrug-resistant NPC cell line that may serve as
      an important tool for research in drug resistance. In addition, the application
      of ZOL may hold clinical therapeutic potential for the treatment of drug
      resistance in NPC.

PMID- 28454333
TI  - A polysaccharide component from Strongylocentrotus nudus eggs inhibited
      hepatocellular carcinoma in mice by activating T lymphocytes.
AB  - A component purified from Strongylocentrotus nudus eggs on a diethylaminoethyl
      cellulose-52 chromatography column and eluted using a NaCl solution gradient (SEP
      S), is a homogeneous polysaccharide of alpha-D-glucan with a reduced molecular
      weight of 9.33*105 Da, compared with that of S. nudus egg polysaccharide (SEP).
      In an in vivo antitumor assay of histocompatibility-22 hepatocellular carcinoma
      in tumor-bearing mice, the inhibitory rates at SEP-S doses of 5, 10 and 20
      mg/kg/day were 38.8, 50.7 and 70.3%, respectively. In addition, the spleen and
      thymus indices and the percentages of cluster of differentiation (CD) 4+ and CD8+
      T cells were significantly increased, and the activity of cytotoxic T lymphocytes
      was notably enhanced, suggesting that the anti-hepatocellular carcinoma activity
      is mediated by boosting the immune system. In vitro experiments also demonstrated
      that splenocyte proliferation induced by SEP-S was inhibited by the toll-like
      receptor (TLR) 2 and TLR4 monoclonal antibodies. These data indicate that SEP-S
      is a polysaccharide component possessing high anti-hepatocellular carcinoma
      activity and may be a potential immunotherapy candidate for the treatment of
      liver cancer.

PMID- 28454334
TI  - Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts
      of breast invasive ductal cancer.
AB  - Breast cancer is the most common malignant tumor in women worldwide, and accounts
      for an estimated 29% of new cases and 15% of cancer-associated mortalities each
      year. Invasive ductal carcinoma represents 70-80% of all breast cancer cases,
      which are responsible for the majority of breast cancer fatalities. Though great
      progress has been made in understanding the tumorigenesis and development of
      breast cancer, problems surrounding treatment persist. It was previously reported
      that carcinoma-associated fibroblasts (CAFs) may be closely associated with
      chemotherapy resistance. In the present study, primary-cultured CAFs from
      surgically resected breast invasive ductal cancer tissues were prepared and
      tested to clarify the change of gene expression profile following treatment with
      20 ng/ml Taxotere(r) for 24 h through microarray analysis. In addition,
      quantitative polymerase chain reaction and western blotting were performed to
      compare the gene and protein expression of the candidate gene in CAFs prior to
      and following Taxotere treatment. Based on the obtained data, 35 differentially
      expressed genes were identified, including ACTA2, ACTC1, ACTG, ALDH1B1, AMY1A,
      C5orf13, CNN1, CXCR7, DDAH1, FGF1, PDLIM3, MAMLD1, MYH11, OXTR, PDLIM5, RARRES1,
      SERPINA3, TRIL, C14orf43, C1orf51, CXCL12, CXCL2, EGR2, EGR3, IER3, interleukin
      (IL)8, IRF1, JUNB, MMP1, NAV2, NFKBIA, NFKBIZ, TRIB1, WNT16 and ZC3H12A. It was
      observed that the expression of the candidate gene IL8 in the CAFs of breast
      invasive cancer following treatment with Taxotere was increased (P<0.05).
      Overall, elevated expression of IL8 induced by Taxotere in CAFs potentially
      supports the association between IL8 and chemotherapy response.

PMID- 28454335
TI  - Effect of laser therapy on plasma expression of VEGF and bFGF in infants with
      cutaneous hemangioma.
AB  - The present study aimed to investigate the effect of laser therapy on the
      expression of vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor (bFGF) in the plasma of infants diagnosed with cutaneous
      hemangioma, in order to identify biomarkers for assessing the clinical efficacy
      of laser therapy. In total, 109 infants with superficial abdominal hemangioma
      received laser treatment, of which 74 were diagnosed in the proliferation phase,
      20 in the regression phase and 15 in the involution phase. In addition, 10
      infants without cutaneous hemangioma were recruited as normal controls. The
      concentrations of VEGF and bFGF in peripheral plasma samples were measured using
      ELISAs. Dynamic changes in the VEGF and bFGF concentrations of 23 infants
      diagnosed in the proliferation phase were compared before and after laser
      therapy. The plasma concentration of VEGF in the proliferation phase group was
      significantly higher compared with that in the regression phase, involution phase
      and normal control groups (all P<0.01), whereas it did not differ significantly
      among the regression phase, involution phase and normal control groups (all
      P>0.05). The plasma concentration of bFGF in the proliferation phase group was
      significantly higher compared with that in the regression phase, involution phase
      and normal control groups (all P<0.01), while the bFGF level did not differ
      significantly among the regression phase, involution phase and normal control
      groups (all P>0.05). Following laser therapy, the plasma concentrations of VEGF
      and bFGF in infants with cutaneous hemangioma were significantly decreased (both
      P<0.01). These results suggested that VEGF and bFGF may serve as reliable indexes
      to evaluate the clinical efficacy of laser therapy for treating infantile
      cutaneous hemangioma.

PMID- 28454336
TI  - Promoter methylation and expression of Raf kinase inhibitory protein in
      esophageal squamous cell carcinoma.
AB  - Raf kinase inhibitory protein (RKIP) regulates multiple cellular processes, and
      its downregulation is associated with distinct human cancers. In the present
      study, the status of RKIP promoter methylation, as well as its expression and
      clinical significance in esophageal squamous cell carcinoma (ESCC), were
      examined. The promoter methylation status in the 5'-CpG island of the RKIP gene
      and the expression level of the RKIP protein were examined using a modified
      methylation-specific polymerase chain reaction (MSP) method and
      immunohistochemical staining, respectively, in 77 ESCC samples and matched
      paratumor normal tissues. The incidence of RKIP promoter methylation was
      significantly higher in tumor samples (75.3%) than in the matched normal tissues
      (27.3%; P<0.001). A higher incidence of promoter methylation was also detected in
      poorly differentiated cancers (93.5%) compared with well-differentiated cancers
      (50.0%; P<0.001), as well as in tumor samples with positive lymph node metastasis
      (86.7%) compared with those with negative lymph node metastasis (59.4%; P<0.001).
      Consistent with the promoter methylation status, the expression level of RKIP was
      significantly reduced in cancer tissues (36.4%) compared with matched normal
      tissues (76.6%; P<0.01), as well as in cancers with positive lymph node
      metastasis (24.4%) compared with those with negative lymph node metastasis
      (53.1%; P=0.01). Promoter methylation-induced gene silencing significantly
      correlated with the down regulation of RKIP and the development of ESCC. The
      results of the present study suggested that the methylation status of the RKIP
      promoter, when combined with its expression level, may serve as a biomarker for
      predicting the biological behaviors of ESCC.

PMID- 28454337
TI  - Inhibitory effect of Ginkgol C17:1 on the biological behavior of tumor cells.
AB  - Ginkgol C17:1 is a bioactive compound derived from Ginkgo biloba. In the present
      study, the effect and possible mechanisms of action of Ginkgol C17:1 on the
      biological behaviors of tumor cells were investigated. Whilst cell proliferation
      was assessed using the MTT assay, the behaviors of cell migration and invasion
      were explored using Transwell and modified Transwell assays. The results revealed
      that Ginkgol C17:1 significantly inhibited the proliferation, migration and
      invasion of human tumor cells in a dose-dependent manner. Furthermore, due to
      their associations with the biological behaviors of tumor cells, the protein
      expression of matrix metalloproteinase (MMP)-7, Ras homolog gene family, member A
      (RhoA) and phosphorylated-protein kinase B (Akt) was analyzed by western
      blotting. The results showed that the expression of the aforementioned proteins
      was decreased markedly following Ginkgol C17:1 treatment. The results of the
      present study suggested that Ginkgol C17:1 suppresses the biological behaviors of
      tumor cells by inhibiting the activation of the mitogen-activated protein
      kinase/MMP, Rho/Rho-associated protein kinase and phosphatidylinositol 3
      kinase/Akt signaling pathways.

PMID- 28454338
TI  - Ellagic acid and Annona muricata in the chemoprevention of HPV-related pre
      neoplastic lesions of the cervix.
AB  - Ellagic acid is a phenolic compound naturally present in nuts and berries.
      Several studies have demonstrated that this bioactive compound has antioxidant,
      chemopreventive and antiviral activity. Annona muricata is a type of fruit tree
      with a long history of traditional use. A number of properties have been
      attributed to different parts of the plant, including anticancer and antioxidant
      activities. In the current study, a complex based on ellagic acid, Annona
      Muricata and antioxidant factors (an ellagic acid complex) was administered to a
      group of human papilloma virus (HPV) infected women with and without cervical
      lesions, for 12 months. Its effect on HPV clearance and cervical cytological
      outcomes was assessed and a group of women with the same clinical features who
      did not receive the ellagic acid complex served as a control. A positive
      correlation was observed between intake of ellagic acid complex and negative Pap
      test following 6 and 12 months of treatment (chi2 test: 0.041 and 0.014,
      respectively). Women treated with the ellagic acid complex were less likely to be
      diagnosed with an abnormal Pap smear at 6 months [Odds ratio (OR): 0.39; 95%
      confidence interval (CI) 0.14-1.06] and 12 months (OR: 0.35; 95% CI 0.13-0.89),
      compared with the control group. After adjusting for confounding factors
      including age and smoking habit, this association remained significant. No effect
      was observed on HPV clearance or viral integration. The data from the current
      study suggest a protective effect of the ellagic acid complex on cervical cells,
      possibly through apoptosis, cell cycle arrest and repair mechanisms.

PMID- 28454340
TI  - Characterization of topoisomerase II alpha and minichromosome maintenance protein
      2 expression in anal carcinoma.
AB  - The present study aimed to ascertain the significance of topoisomerase II alpha
      (TOP2A) and minichromosome maintenance protein (MCM) 2 expression in anal
      carcinoma. A total of 75 anal lesions were retrieved from the files of the
      Department of Pathology of Barretos Cancer Hospital (Barretos, Brazil) in order
      to verify the human papillomavirus (HPV) statuses of these lesions and
      characterize the immunohistochemical expression levels of TOP2A and MCM2 in anal
      carcinoma, as these are important markers for cervical HPV-induced lesions; their
      expression was also compared with respect to p16 and Ki-67. The vast majority of
      the cases tested positive for HPV16 (84%); 1 case tested positive for both HPV16
      and HPV18. Positive HPV16 status was more frequent in early stages than in
      advanced stages (P=0.008). Positive immunohistochemical reactivity for MCM2 and
      TOP2A protein was observed in 71.6 and 100% of cases, respectively. Positive
      reactivity for p16 was significantly associated (P=0.001) with histological
      grade, and was more commonly expressed in squamous cell carcinoma than
      adenocarcinomas. HPV16 was strongly associated with positive p16 protein
      expression (76.6%). However, the high expression of Ki-67 combined with the high
      expression of p16 was predominantly observed in Stage III-IV cases. MCM2, TOP2A,
      p16 and Ki-67 exhibited intense positive staining in the anal lesions, indicating
      that these markers were significantly and constantly expressed in anal carcinoma.

PMID- 28454339
TI  - PUMA decreases the growth of prostate cancer PC-3 cells independent of p53.
AB  - PUMA (p53 upregulated modulator of apoptosis), a member of the B-cell lymphoma 2
      (Bcl-2) protein family, is a pro-apoptotic protein. PUMA expression is modulated
      by the tumor suppressor p53. PUMA has a role in rapid cell death via p53
      dependent and -independent mechanisms. To evaluate whether p53 is required for
      PUMA-mediated apoptosis in prostate cancer cells, p53 protein was silenced in
      human prostate cancer PC-3 cells by using p53 small interfering RNA (siRNA). The
      interference efficiency of p53 on RNA and protein levels was detected by reverse
      transcription-quantitative polymerase chain reaction and western blotting. Cell
      proliferation and p21 expression were subsequently examined by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and western
      blot analysis, respectively. p53-silenced or control PC-3 cells were transfected
      with pCEP4-(hemagglutinin)-PUMA plasmid, or non-carrier plasmid. Enzyme-linked
      immunosorbent assay was used to determine cell apoptosis by measuring histone
      release and caspase-3 activation, and MTT assay was used to measure cell
      viability. In addition, the expression of pro-apoptosis protein Bax and anti
      apoptosis protein Bcl-2 were evaluated. The results of the present study revealed
      that p53 siRNA significantly suppressed p53 RNA and protein expression in PC-3
      cells. Deficiency of p53 increased the cell growth rate and decreased p21
      expression. However, PUMA overexpression remained able to induce apoptosis in p53
      silenced and control cells by increasing Bax expression and decreasing Bcl-2
      expression, leading to the activation of caspase-3. These results suggest that
      PUMA may mediate apoptosis of prostate cancer PC-3 cells, potentially
      independently of p53. Furthermore, PUMA gene treatment to induce cancer cell
      apoptosis may be more efficient compared with p53-dependent apoptosis, where loss
      of p53 expression or function may lead to limited efficacy of PUMA expression.
      Therefore, the present study proposes the significant hypothesis that increasing
      PUMA expression may be an effective approach for the treatment of prostate
      cancer, regardless of p53 status.

PMID- 28454341
TI  - The role of FADD in pancreatic cancer cell proliferation and drug resistance.
AB  - Pancreatic cancer has one of the poorest patient outcomes and is highly resistant
      to chemotherapy. Identifying the molecular mechanisms involved in drug resistance
      is critical in the development of novel strategies to treat pancreatic cancer.
      The results of the present study demonstrate that Fas-associated death domain
      protein (FADD), a classical adaptor protein mediating apoptotic stimuli-induced
      cell death, protects pancreatic cancer cells from drug-induced apoptosis. In
      contrast to its classical apoptotic roles, it was observed that FADD is required
      for pancreatic cancer cell proliferation and that it is overexpressed to varying
      degrees in various types of pancreatic cancer cell. This leads to differing
      levels of drug resistance in pancreatic cancer cells, where drug resistance is
      positively correlated with FADD expression. Notably, the results of the present
      study demonstrate that FADD protects pancreatic cancer cells from drug-induced
      apoptosis, while RNA interference of FADD sensitizes drug-resistant cells to
      Adriamycin(r)-mediated apoptosis. The results of the present study reveal
      unexpected roles for FADD in pancreatic cancer cell proliferation and drug
      resistance.

PMID- 28454342
TI  - Feasibility and antitumor efficacy in vivo, of simultaneously targeting
      glycolysis, glutaminolysis and fatty acid synthesis using lonidamine, 6-diazo-5
      oxo-L-norleucine and orlistat in colon cancer.
AB  - The aim of the present study was to investigate in vivo the feasibility and
      efficacy of the combination of lonidamine (LND), 6-diazo-5-oxo-L-norleucine (DON)
      and orlistat to simultaneously target glycolysis, glutaminolysis and de novo
      synthesis of fatty acids, respectively. The doses of LND and DON used in humans
      were translated to mouse doses (77.7 mg/kg and 145.5 mg/kg, respectively) and
      orlistat was used at 240 mg/kg. Three schedules of LND, DON and orlistat at
      different doses were administered by intraperitoneal injection to BALB/c mice in
      a 21-day cycle (schedule 1: LND, 0.5 mg/day; DON, 0.25 mg/day 1, 5 and 9;
      orlistat, 240 mg/kg/day; schedule 2: LND, 0.1 mg/day; DON, 0.5 mg/day 1, 5 and 9;
      orlistat, 240 mg/kg/day; schedule 3: LND, 0.5 mg/day; DON, 0.08 mg/day 1, 5 and
      9; orlistat, 360 mg/kg/day) to assess tolerability. To determine the antitumor
      efficacy, a syngeneic tumor model in BALB/c mice was created using colon cancer
      CT26.WT cells, and a xenogeneic tumor model was created in nude mice using the
      human colon cancer SW480 cell line. Mice were treated with schedule 1. Animals
      were weighed, clinically inspected during the experiment and the tumor volume was
      measured at day 21. The 3 schedules assessed in the tolerability experiments were
      well tolerated, as mice maintained their weight and no evident clinical signs of
      toxicity were observed. Combination treatment with schedule 1 significantly
      decreased tumor growth in each mouse model. No evident signs of toxicity were
      observed and mice maintained their weight during treatment. The triple metabolic
      blockade of the malignant phenotype appears feasible and promising for cancer
      therapy.

PMID- 28454343
TI  - Promoter hypermethylation of the RECK gene is associated with its low expression
      and poor survival of esophageal squamous cell carcinoma.
AB  - The present study aimed to investigate the association between the methylation
      status of the reversion-inducing cysteine-rich protein with kazal motifs (RECK)
      gene and its mRNA expression levels in patients with esophageal squamous cell
      carcinoma (ESCC). The methylation status of RECK was analyzed by methylation
      specific polymerase chain reaction (PCR), and RECK mRNA expression levels were
      analyzed by quantitative PCR, in 310 paired ESCC tissues. The mean RECK
      methylation index (MI) was 0.65 in ESCCs and 0.49 in non-tumor samples. There was
      a significant association between RECK methylation and the American Joint
      Committee on Cancer stage and lymph node metastasis in ESCC (P<0.0001; P=0.001).
      The mRNA expression level of RECK was lower in ESCC tissues (mean-?Cq=-4.66)
      compared with non-tumor tissues (mean-?Cq=-2.79), and decreased RECK mRNA
      expression levels were associated with lymph node metastasis in ESCC. In
      addition, RECK mRNA levels were decreased in ESCC patients with hypermethylation
      of the RECK gene (?MI >0.16; mean-??Cq=-2.85) compared with those with
      hypomethylation of the RECK gene (?MI <=0.16; mean-??Ct=-0.83), and there was a
      significant difference in the mRNA expression levels of RECK between those with
      N0-1 and N2-3 lymph node metastasis (P<0.0001). A significant correlation was
      observed between RECK mRNA expression levels, the MI of RECK and poor
      postoperative survival (P=0.0003; P<0.0001). The results of the present study
      suggested that promoter hypermethylation may be an important factor for loss of
      RECK mRNA expression and may be an indicator of poor survival in ESCC.

PMID- 28454344
TI  - Galectin-7 promotes the invasiveness of human oral squamous cell carcinoma cells
      via activation of ERK and JNK signaling.
AB  - Galectin-7 is a member of the beta-galactoside-binding protein family, and is
      highly expressed in oral squamous cell carcinoma (OSCC). The aim of the present
      study was to investigate the effects of manipulating galectin-7 expression on the
      biological phenotype of human OSCC cells and the associated molecular mechanisms.
      Knockdown of endogenous galectin-7 via small interfering RNA (siRNA) was
      performed and cell proliferation, apoptosis, migration, and invasion were
      subsequently assessed. The data indicated that galectin-7 silencing had no impact
      on the proliferation or apoptosis of OSCC cells. However, compared with non
      transfected cells, percentage wound closure was significantly lower in galectin-7
      silenced cells following 24 h incubation, indicating decreased cell migration.
      Furthermore, Matrigel invasion assays demonstrated that galectin-7 knockdown
      significantly reduced the number of invaded cells, compared with the number in
      non-transfected cells. Western blot analysis indicated that galectin-7
      overexpression resulted in a significant increase in the expression of the
      proteins matrix metalloproteinase (MMP)-2 and MMP-9. The invasive abilities of
      cells overexpressing galectin-7 significantly decreased following co-transfection
      with MMP-2- or MMP-9-specific siRNA. Increasing galectin-7 expression
      significantly enhanced the phosphorylation of extracellular signal-related kinase
      (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2. Pharmacological inhibition of
      ERK or JNK activity significantly suppressed the invasiveness of galectin-7
      overexpressing cells and abrogated the upregulation of MMP-2 and MMP-9. Taken
      together, the results of the current study provide novel evidence for the pro
      invasive activity of galectin-7 in OSCC cells, which is associated with
      activation of ERK and JNK signaling and the induction of MMP-2 and MMP-9.

PMID- 28454345
TI  - High IL-17 expression is associated with an unfavorable prognosis in thyroid
      cancer.
AB  - Previous studies have indicated that cancer may be promoted and/or exacerbated by
      inflammation and infection. The cytokines produced by activated innate immune
      cells that stimulate tumor growth and progression are considered as important
      components in this process. The interleukin (IL)-23/T helper (Th)17 axis, which
      exerts marked pro-inflammatory effects, has emerged as an important mediator in
      inflammation-associated cancer. Increasing clinical evidence indicates that Th17
      may promote or inhibit tumor progression, however, the function of Th17 in the
      pathogenesis of benign and malignant thyroid neoplasms remains unclear. The
      present study investigated the association between the IL-23/Th17 axis and
      neoplastic and non-neoplastic thyroid lesions using immunohistochemistry. A total
      of 131 thyroid biopsy specimens were analyzed, which revealed high IL-17 and IL
      23 expression in differentiated thyroid cancer and medullary thyroid cancer
      tissues when compared with benign lesions, including follicular thyroid adenoma
      and goiter tissues. Furthermore, high IL-17 expression was associated with
      recurrence and mortality. These results indicate that the IL-23/Th17 axis
      exhibits a pivotal function in the development of thyroid neoplasms.

PMID- 28454346
TI  - MicroRNA-134 targets KRAS to suppress breast cancer cell proliferation, migration
      and invasion.
AB  - The expression patterns and functions of microRNA-134 (miR-134) have been
      previously studied in numerous types of cancer. To the best of our knowledge,
      this is the first study of miR-134 in human breast cancer. In the present study,
      the expression patterns, biological functions and underlying molecular mechanisms
      of miR-134 in human breast cancer were investigated. Reverse transcription
      quantitative polymerase chain reaction evaluated the expression of miR-134 in
      human breast cancer tissues, matched normal adjacent tissues, breast cancer cell
      lines and a normal mammary epithelial cell line. Following transfection with miR
      134, an MTT assay, cell migration assay, cell invasion assay, western blot
      analysis and a luciferase assay were performed on the MCF-7 and MDA-MB-231 human
      breast cancer cell lines. The findings revealed that miR-134 expression levels
      were significantly downregulated in breast cancer cells. Statistical analysis
      demonstrated that low expression of miR-134 was significantly associated with
      lymph node metastasis, TNM stage and reduced cell differentiation. It was
      observed that miR-134 inhibited the growth, migration and invasion of breast
      cancer cells. Additionally, the present study indicated that miR-134 may directly
      target the Kirsten rat sarcoma viral oncogene homolog in breast cancer tissues.
      These results suggest that miR-134 may be used as a potential therapeutic
      biomarker in breast cancers.

PMID- 28454347
TI  - Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic
      cell proliferation.
AB  - Pancreatic cancer is the fourth leading cause of cancer-associated mortality. The
      major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are
      commonly observed in human pancreatic cancers. The present study examined the
      hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras
      gene in the pancreas affects pancreatic cell proliferation in mice. Mice
      overexpressing the mutant Kras gene (KRasG12D) in the pancreas as well as wild
      type mice were exposed to environmental tobacco smoke for 2 weeks. Overexpression
      of mutant Kras increased cell proliferation in pancreatic ductal, acinar and
      islet cells. Notably, cigarette smoke exposure decreased cell proliferation in
      pancreatic ductal and acinar cells, and had no effect in islet cells. Cigarette
      smoke did not affect pancreatic protein levels of tumor necrosis factor
      (TNF)alpha, p53, or cyclin D1, but mutant Kras overexpression slightly decreased
      TNFalpha and p53 protein levels. Therefore, pancreatic cell proliferation in mice
      overexpressing mutant Kras is associated with the later development of pancreatic
      tumors, but effects of cigarette smoke on pancreatic cell proliferation do not
      provide a good model for human pancreatic carcinogenesis.

PMID- 28454348
TI  - Effects of PTCs on nonsense-mediated mRNA decay are dependent on PTC location.
AB  - The recepteur d'origine nantais (RON) gene is a proto-oncogene that is
      responsible for encoding the human macrophage-stimulating protein (MSP) 1
      receptor. MSP activation induces RON-mediated cell dissociation, migration and
      matrix invasion. Isoforms of RON that exclude exons 5 and 6 encode the
      RONDelta160 protein, which promotes cell transformation in vitro and tumor
      metastasis in vivo. Premature termination codons (PTCs) in exons activate the
      nonsense-mediated mRNA decay (NMD) signaling pathway. The present study
      demonstrated that PTCs at various locations in the alternative exons 5 and 6
      could induce NMD of the majority of the spliced, or partially spliced, isoforms.
      However, the isoforms that excluded exon 6 or exons 5 and 6 were markedly
      increased when produced from mutated minigenes with inserted PTCs. Furthermore,
      the unspliced isoform of intron 5 was not observed to be decreased by the
      presence of PTCs. Notably, these effects may be dependent on the location of the
      PTCs. The current study demonstrated a novel mechanism underlying the regulation
      of NMD in alternative splicing.

PMID- 28454349
TI  - Low serum testosterone is associated with tumor aggressiveness and poor prognosis
      in prostate cancer.
AB  - Serum testosterone is a potential marker to distinguish between indolent and
      aggressive prostate cancer (PCa). The present study aimed to investigate whether
      low levels of total serum testosterone at diagnosis were associated with
      aggressive PCa and poor clinical outcomes. In total, 762 non-Hispanic Caucasian
      men with previously untreated PCa were recruited from The University of Texas MD
      Anderson Cancer Center (Houston, TX, USA). Patients were categorized into three
      groups based on their total serum testosterone levels according to clinical
      guidelines [low (<230 ng/dl), intermediate (230-350 ng/dl) and normal (>350
      ng/dl)]. PCa aggressiveness (low-, intermediate- or high-risk, or metastatic) was
      compared using multinomial logistic regression. Rates of disease progression,
      mortality from any cause and PCa-specific mortality were compared using the
      multivariate Cox proportional hazards model. Testosterone levels significantly
      decreased as PCa aggressiveness increased (P<0.001). Compared with the normal
      testosterone group, the low testosterone group had 2.9-fold (OR, 2.92; 95% CI,
      1.74-4.90; P<0.001), 5.6-fold (OR, 5.63; 95% CI, 3.14-10.12; P<0.001) and 72.4
      fold (OR, 72.40; 95% CI, 20.89-250.89; P<0.001) increased risks of having
      intermediate-risk, high-risk and metastatic PCa, respectively. Furthermore, low
      levels of testosterone were significantly associated with a 10.7-fold (HR, 10.68;
      95% CI, 1.35-84.44; P=0.03) increased risk of PCa-specific mortality. The results
      of the present study indicate that low levels of total serum testosterone at
      diagnosis are associated with aggressive PCa and predict poor PCa-specific
      survival.

PMID- 28454350
TI  - miR-455-5p functions as a potential oncogene by targeting galectin-9 in colon
      cancer.
AB  - Although there is evidence that galectin-9 is a critical factor in health and
      disease, the upstream regulatory microRNA (miRNA or miR) of the protein remains
      poorly defined. miR-455-5p is characterized as a tumor-associated miRNA in cancer
      research. However, the actual role of miR-455-5p with respect to inhibiting or
      promoting tumorigenesis in colon cancer is unclear. The present study aimed to
      investigate the expression, role and target regulation association of galectin-9
      and miR-455-5p in colon cancer. Western blot analysis and reverse transcription
      quantitative polymerase chain reaction were used for the detection of the
      expression levels of galectin-9 and miRNAs. Cell Counting kit-8 test was used for
      the evaluation of cell proliferation, while flow cytometry was used for cell
      apoptosis analysis. A potential interaction between galectin-9 and miR-455-5p was
      predicted by target prediction programs and confirmed by luciferase assay and
      transfection with miRNA mimics. The present study revealed that elevated
      expression of galectin-9 and miR-455-5p in colon cancer was associated with HT29
      cell proliferation and apoptosis. Furthermore, the present study demonstrated
      that miR-455-5p reduced galectin-9 expression by directly targeting its 3'
      untranslated region. These data suggest that miR-455-5p functions as a potential
      oncogene in colon cancer by targeting galectin-9.

PMID- 28454351
TI  - The role of quercetin and vitamin C in Nrf2-dependent oxidative stress production
      in breast cancer cells.
AB  - The balance between the production and elimination of reactive oxygen species
      (ROS) is essential in determining whether cells survive or undergo apoptosis.
      Nuclear factor erythroid 2-related factor 2 (Nrf2) may act as a sensor for
      electrophilic stress, thus regulating the intracellular antioxidant response. The
      present study investigated the role of vitamin C (VC) and quercetin (Q) in the
      induction of Nrf2-mediated oxidative stress in cancer cells. An MTT assay was
      conducted to examine the anti-proliferative effects of VC and Q. Reverse
      transcription-quantitative polymerase chain reaction and western blot analysis
      were performed to determine the messenger RNA (mRNA) and protein expression of
      Nrf2, respectively. The activity of nicotinamide adenine dinucleotide phosphate
      dehydrogenase quinone 1, heme oxygenase 1, glutathione peroxidase, glutathione
      reductase and reduced glutathione were measured by spectrophotometric analysis.
      Intracellular generation of ROS was determined using 2'-7'
      dichlorodihydrofluorescein diacetate fluorescent probes. The results demonstrated
      that the cytotoxicity (50% inhibitory concentration) of VC and Q were 271.6-480.1
      and 155.1-232.9 uM, respectively. Additionally, there was a significant decrease
      in the expression of Nrf2 mRNA and protein levels following the treatment of
      breast cancer cells with VC and Q (P=0.024). Following treatment with VC and Q,
      the nuclear/cytosolic Nrf2 ratio was reduced by 1.7-fold in MDA-MB 231 cells, 2
      fold in MDA-MB 468 cells, 1.4-fold in MCF-7 cells and 1.2 fold in A549 cells.
      Sequential treatment with VC and Q decreased endogenous production of ROS in a
      dose-dependent manner (P=0.027). The results of the current study suggest that VC
      and Q treatment may be developed as an adjuvant for patients with cancer and
      overexpression of Nrf2.

PMID- 28454352
TI  - Analysis of circulating adipokines in patients newly diagnosed with solid cancer:
      Associations with measures of adiposity and tumor characteristics.
AB  - The development and progression of cancer is a complex and multifactorial process
      and the global prevalence of obesity is markedly increasing. A number of studies
      have made an association between obesity and increased rates of epithelial
      tumors. Obesity is associated with altered adipokine levels, potentially
      contributing to the process of tumor development and metastasis. In the current
      study, the associations between circulating adipokines and measures of adiposity
      and tumor characteristics among patients diagnosed with solid malignancies were
      examined at the time of presentation, and following the administration of
      chemotherapy. A total of 30 patients with cancer and matched healthy controls
      were enrolled in the present study. Plasma adipokine levels of hepatocyte growth
      factor (HGF), adiponectin and leptin were determined using commercially available
      ELISA kits. At baseline, plasma HGF, adiponectin and leptin levels were not
      significantly different between patients with cancer and the healthy controls.
      Circulating HGF levels were significantly associated with the stage of cancer at
      diagnosis (P=0.044), but lacked a significant association with lymph node status
      (P=0.194). Plasma adiponectin and leptin levels were not significantly associated
      with tumor characteristics at the time of diagnosis. Only leptin was positively
      correlated with the body mass index of patients with cancer (P<0.001). No
      significant correlations were detected between the evaluated adipokines and
      measures of visceral obesity, as determined by waist circumference and the waist
      hip ratio at presentation. Following administration of chemotherapy, adiponectin
      was the only adipokine evaluated in the current study that exhibited a
      significant difference, when compared with baseline plasma levels (P=0.013), and
      a significant positive correlation between baseline and follow-up circulating
      levels (P=0.002) among patients with cancer. In addition, there were no
      significant inter-correlations between circulating adipokines at baseline level
      and during follow-up in patients with cancer. Collectively, the findings of the
      current study suggest a lack of diagnostic roles for the adipokines investigated
      and no significant association with measures of adiposity. Adiponectin may be a
      potential adipokine to measure in patients with cancer, in order to further
      assess its prognostic and predictive potential.

PMID- 28454353
TI  - PRMT8 demonstrates variant-specific expression in cancer cells and correlates
      with patient survival in breast, ovarian and gastric cancer.
AB  - Recent emphasis has been placed on the role of epigenetic regulators and
      epigenetic marks as biomarkers for cancer diagnosis and prognosis, and as
      therapeutic targets for treatment. One such class of regulators is the protein
      arginine methyltransferase (PRMT) family. The present study examined available
      curated data regarding the expression and alteration of one of the least studied
      PRMT family members, PRMT8, in various types of cancer and cancer cell lines.
      Publicly available cancer data on PRMT8 expression were examined using the Human
      Protein Atlas and the Kaplan-Meier Plotter, and reverse transcription-polymerase
      chain reaction was used to screen a selection of human cell lines for variant
      specific PRMT8 expression. High levels of PRMT8 expression in breast, ovarian and
      cervical cancer was observed. Additionally, in patients with breast and ovarian
      cancer, high PRMT8 expression was correlated with increased patient survival,
      whereas in gastric cancer, high PRMT8 expression was correlated with decreased
      patient survival. The present study also investigated the expression of PRMT8
      variant 2, a novel transcript variant recently identified in our laboratory, in
      various cancer cell lines. Variant-specific expression of PRMT8 in numerous
      distinct cancer cell lines derived from different tissues, including the
      expression of the novel PRMT8 variant 2 in U87MG glioblastoma cells was
      demonstrated. The present study proposes the possibility of PRMT8 as a cancer
      biomarker, based on the high level of PRMT8 expression in various types of
      cancer, particularly in tissues that would not normally be expected to express
      PRMT8, and on the correlation of PRMT8 and patient lifespan in several cancer
      types. Variant-specific expression of PRMT8 in diverse cancer cell lines suggests
      the possibility of alternate PRMT8 isoforms to have diverse effects on cancer
      cell phenotypes.

PMID- 28454354
TI  - PT93, a novel caffeic acid amide derivative, suppresses glioblastoma cells
      migration, proliferation and MMP-2/-9 expression.
AB  - Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor
      in adults and can diffusely infiltrate adjacent normal tissue. GBM is therefore
      rarely cured by surgery or radiation therapy. Matrix metalloproteinases (MMPs)
      are involved in tissue remodeling and numerous other physiological progresses.
      The MMPs MMP-2 and MMP-9 are associated with the invasion ability of GBM. PT93 is
      a novel caffeic acid amide derivative that was first synthesized in 2013. In the
      present study, the human GBM T98G, U87 and U251 cell lines and the normal mouse
      neuron HT22 cell line were used to investigate the anticancer and cytotoxic
      effects of PT93 in vitro. The cytotoxicity of PT93 was measured using MTT and
      lactate dehydrogenase assays. The anti-proliferation effect was tested using a
      cell colony formation assay. Gelatin zymography analysis and a scratch test were
      used to investigate the anti-migration mechanism of PT93. Western blot analysis
      was used to measure the expression of MMP-2/-9. The experimental results showed
      that PT93 suppressed the proliferation of T98G cells, and showed cytotoxicity
      effects at high concentration in T98G, U87, U251 and HT22 cell lines.
      Furthermore, PT93 limited the migration ability of the cells and inhibited the
      extracellular MMP-2 and MMP-9 activity of T98G and U251 cells. Finally, the
      present study confirmed that PT93 affects the level of MMP-2/-9 expression in
      T98G cells in a concentration-dependent manner. The present study indicates that
      PT93, as a novel caffeic acid amide derivative, may be used in the treatment of
      GBM.

PMID- 28454356
TI  - Harnessing antitumor immunity: Employment of tumor recall antigens to optimize
      the inflammatory response to cancer.
AB  - The advent of immunotherapy for cancer has contributed to the era of personalized
      medicine for cancer. The various immunotherapy-based treatments that have been
      explored thus far include monoclonal antibody therapy, tumor vaccines, immune
      checkpoint blockade and adoptive T cell transfer, among others. The groundwork
      for all these immunotherapeutic modalities rests within the tumor
      microenvironment, specifically the immune factors that influence the tumor-drug
      interface. Prior to therapeutic design, the tumor microenvironmental interactions
      and the current barriers to successful treatment must first be understood. In the
      present review, it is proposed that cancer cell eradication within the tumor
      niche may be achieved by reprogramming of the immune microenvironment in favor of
      a pro-inflammatory antitumor profile at an early stage. This pro-inflammatory
      profile may, in turn, be influenced by tumor recall antigens, which function to
      stimulate the cell-mediated or humoral responses involved in antitumor immunity.
      These measures serve to counteract the immunotolerant state of the tumor
      microenvironment. Such measures are critical to therapeutic successes.

PMID- 28454355
TI  - What is known about melatonin, chemotherapy and altered gene expression in breast
      cancer.
AB  - Melatonin, synthesized in and released from the pineal gland, has been
      demonstrated by multiple in vivo and in vitro studies to have an oncostatic role
      in hormone-dependent tumors. Furthermore, several clinical trials point to
      melatonin as a promising adjuvant molecule to be considered for cancer treatment.
      In the past few years, evidence of a broader spectrum of action of melatonin as
      an antitumor agent has arisen; thus, melatonin appears to also have therapeutic
      effects in several types of hormone-independent cancer, including ovarian,
      leukemic, pancreatic, gastric and non-small cell lung carcinoma. In the present
      study, the latest findings regarding melatonin molecular actions when
      concomitantly administered with either radiotherapy or chemotherapy in cancer
      were reviewed, with a particular focus on hormone-dependent breast cancer.
      Finally, the present study discusses which direction should be followed in the
      next years to definitely clarify whether or not melatonin administration could
      protect against non-desirable effects (such as altered gene expression and post
      translational protein modifications) caused by chemotherapy or radiotherapy
      treatments. As treatments move towards personalized medicine, comparative gene
      expression profiling with and without melatonin may be a powerful tool to better
      understand the antitumor effects of melatonin, the pineal gland hormone.

PMID- 28454357
TI  - Expression, regulation and function of miR-495 in healthy and tumor tissues.
AB  - MicroRNA-495 (miR-495) is a small non-coding RNA encoded by a gene located on
      chromosome 14 (14q32.31). Its expression is regulated by the transcription
      factors EF12 and EF47, in addition to promoter methylation status and the fusion
      oncoprotein mixed-lineage leukemia-AF9. Previous studies suggest that miR-495 is
      involved in various developmental, immunological and inflammatory processes in
      healthy tissue, and in the proliferation, invasion, metastasis and drug
      resistance of cancer cells. The role miR-495 serves in tumors is controversial.
      miR-495 primarily functions as a tumor suppressor; however, in a number of cases
      it acts as an oncogene. miR-495 has potential applications as a diagnostic and
      prognostic marker, and as a therapeutic target for genetic and pharmacological
      manipulation in the treatment of various diseases.

PMID- 28454358
TI  - Prognostic relevance of DNA flow cytometry in breast cancer revisited: The 25
      year experience of the Portuguese Institute of Oncology of Lisbon.
AB  - The potential prognostic significance of DNA flow cytometric measurements (DNA
      ploidy and S-phase fraction) in breast cancer remains in dispute. Inconclusive
      data, primarily due to the lack of consistent standardization and quality control
      programs, have limited its translation into clinical practice. The aim of the
      present review, based on the 25-year experience of the Portuguese Institute of
      Oncology of Lisbon, is to assess the clinical relevance and application of DNA
      flow cytometry for the prognosis of breast cancer. Overall, data from Portuguese
      Institute of Oncology of Lisbon indicate that DNA flow cytometry provides
      significant prognostic information that is biologically relevant and clinically
      useful for the management of patients with breast cancer. Furthermore, this data
      has demonstrated the independent value of DNA aneuploidy as a prognostic
      indicator of poor clinical outcome in various subgroups of patients with early or
      locally advanced breast cancer at short- and long-term follow-up. Notably,
      aneuploidy identifies subsets of patients with grade (G)1 or G2 tumours who
      exhibit a poor clinical outcome. These patients may benefit from adjuvant
      chemotherapy, particularly those with luminal A and luminal B/human epidermal
      growth factor-2-negative endocrine-responsive breast cancer. In conclusion, data
      from Portuguese Institute of Oncology of Lisbon reinforces the clinical
      importance and utility of DNA flow cytometric analysis, particularly DNA ploidy,
      in the prognostic assessment and therapeutic planning for patients with breast
      cancer.

PMID- 28454360
TI  - Location of NLS-RARalpha protein in NB4 cell and nude mice.
AB  - In the majority of acute promyelocytic leukemia (APL) cases, translocons produce
      a promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARalpha)
      fusion gene. Studies have reported that neutrophil elastase (NE) cleaves bcr-1
      derived PML-RAalpha in early myeloid cells, leaving only the nuclear localization
      signal (NLS) of PML attached to RARalpha. NLS-RARalpha promotes cell growth and
      inhibits differentiation in response to ATRA. However, the mechanisms by which
      NLS-RARalpha affects cell biological characteristics are yet to be fully
      elucidated. The present study found that the location of RARalphawas altered
      after it was cleaved by NE. Firstly, NE was overexpressed during the preparation
      of recombinant plasmid NB-4/pCMV6-NE-Myc to cleave PML-RARalpha. The total
      protein expression levels of myc and NE and expression levels of NLS-RARalpha in
      nucleoprotein were detected by western blotting. Location of NLS-RARalpha protein
      was detected by immunofluorescence and confocal laser scanning. Secondly, a nude
      mice model was constructed and NE protein, NLS-RARalpha and RARalpha protein
      assays, and the location of NLS-RARalpha and RARalpha proteins were assessed as
      described. The present results showed that, compared with the control groups, the
      location of NLS-RARalpha protein was predominantly detected in the nucleus,
      whereas RARalpha was mainly distributed in the cytoplasm. These findings were
      consistent with those of the nude mice model, and these may be used as a
      foundation to explain the occurrence mechanism of APL.

PMID- 28454359
TI  - Modeling nasopharyngeal carcinoma in three dimensions.
AB  - Nasopharyngeal carcinoma (NPC) is a type of cancer endemic in Asia, including
      Malaysia, Southern China, Hong Kong and Taiwan. Treatment resistance,
      particularly in recurring cases, remains a challenge. Thus, studies to develop
      novel therapeutic agents are important. Potential therapeutic compounds may be
      effectively examined using two-dimensional (2D) cell culture models, three
      dimensional (3D) spheroid models or in vivo animal models. The majority of drug
      assessments for cancers, including for NPC, are currently performed with 2D cell
      culture models. This model offers economical and high-throughput screening
      advantages. However, 2D cell culture models cannot recapitulate the architecture
      and the microenvironment of a tumor. In vivo models may recapitulate certain
      architectural and microenvironmental conditions of a tumor, however, these are
      not feasible for the screening of large numbers of compounds. By contrast, 3D
      spheroid models may be able to recapitulate a physiological microenvironment not
      observed in 2D cell culture models, in addition to avoiding the impediments of in
      vivo animal models. Thus, the 3D spheroid model offers a more representative
      model for the study of NPC growth, invasion and drug response, which may be cost
      effective without forgoing quality.

PMID- 28454361
TI  - MicroRNA-30e-3p inhibits cell invasion and migration in clear cell renal cell
      carcinoma by targeting Snail1.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common type of neoplasm
      affecting the adult kidney. Previous studies on ccRCC have focused on microRNAs,
      a class of small non-coding RNAs that are important in cancer development and
      progression. The present study aimed to investigate the potential role of
      microRNA (miR)-30e-3p in ccRCC. The results revealed that overexpression of miR
      30e-3p in the A498 and 786O ccRCC cell lines was able to inhibit cell invasion
      and migration. The expression level of Snail1, a potential target gene of miR-30e
      3p, was inversely correlated with miR-30e-3p expression in ccRCC tissues and cell
      lines. Furthermore, Snail1 was revealed to be directly regulated by miR-30e-3p
      and had an important role in mediating the biological effects of miR-30e-3p in
      ccRCC. Restoration of Snail1 expression was able to reverse the inhibitory
      properties of miR-30e-3p. Therefore, the results of the current study suggest
      that miR-30e-3p exerts its anticancer functions through direct targeting of
      Snail1 in ccRCC cells, and may be a novel therapeutic agent for this form of
      cancer.

PMID- 28454362
TI  - Growth of tyrosine kinase inhibitor-resistant Philadelphia-positive acute
      lymphoblastic leukemia: Role of bone marrow stromal cells.
AB  - Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine
      kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However,
      there are certain differences in biology between CML and Philadelphia-positive
      acute lymphoblastic leukemia (Ph+ ALL). Little is known about the role and
      mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study co
      cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP
      B15 was detected using a Cell Counting Kit-8. Additionally, quantitative
      polymerase chain reaction and flow cytometry were used to detect the expression
      of the associated genes and proteins. The present study explores the role and
      mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study
      showed that hBMSCs promoted the proliferation of TKI-resistant Ph+ ALL. This was
      shown by the increase in cells in the S+G2-M phase of the cell cycle. It was also
      found that the expression of cyclins A, C, D1 and E was increased. Apoptosis was
      inhibited through upregulation of anti-apoptotic genes [B-cell lymphoma-2 (BCL-2)
      and BCL-extra large] and downregulation of apoptotic genes (BCL-XS, BCL-2
      associated X protein, and caspases 3, 7 and 9). Expression of the breakpoint
      cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL) gene,
      Wnt5a, and Wnt signaling pathway-associated genes (glycogen synthase kinase
      3beta, beta-catenin, E-cadherin and phosphoinositide 3-kinase) and transcription
      factors (c-myc, ephrin type-B2, fibroblast growth factor 20 and matrix
      metalloproteinase 7) was also increased. Furthermore, the expression of drug
      resistance genes (low-density lipoprotein receptor, multidrug resistance
      associated protein and multi-drug resistance gene) was increased and the
      expression of anti-oncogenes (death-associated protein kinase and interferon
      regulatory factor-1) was decreased. It was concluded that hBMSCs promote the
      growth of TKI-resistant Ph+ ALL by these aforementioned mechanisms. Therefore,
      targeting hBMSCs may be a promising approach for preventing the growth of TKI
      resistant Ph+ ALL.

PMID- 28454363
TI  - MicroRNA-124 regulates the radiosensitivity of non-small cell lung cancer cells
      by targeting TXNRD1.
AB  - Radiation treatment remains one of the major modalities in the treatment of lung
      cancer. Although the majority of patients initially respond to treatment with
      radiation, resistance inevitably develops and leads to treatment failure.
      Therefore, the identification of the underlying molecular mechanisms of radiation
      resistance may facilitate the development of novel approaches for overcoming
      resistance, and enhance the efficacy of treatment with radiation in lung and
      other types of cancer. In the present study we established three radiation
      resistant sub-cell lines derived from the radiation-sensitive lung cancer cell
      line HCC827. Using a polymerase chain reaction microRNA (miRNA) array, multiple
      miRNAs were identified to be markedly downregulated in radiation-resistant cells,
      including miRNA (miR)-124, miR-191 and miR-205. It was observed that
      overexpression of miR-124 sensitized the resistant cells to treatment with
      radiation and that thioredoxin reductase 1 (TXNRD1) is a novel target of miR-124.
      Furthermore, it was demonstrated that knockdown of TXNRD1 using small interfering
      RNA increased the basal level of reactive oxygen species and sensitized the cells
      to radiation treatment. The results of the present study demonstrated that
      multiple miRNAs are downregulated in radiation-resistant lung cancer cells and
      that downregulation of miR-124 mediates radiation resistance through the
      targeting of TXNRD1 mRNA expression. The present study revealed a novel molecular
      mechanism of miRNA-mediated radiation resistance and identified miR-124-regulated
      TXNRD1 as a novel therapeutic target for overcoming radiation resistance in the
      treatment of lung cancer.

PMID- 28454364
TI  - Personalized therapy tests for the monitoring of chronic lymphocytic leukemia
      development.
AB  - There is individual variation in the course of disease development and response
      to therapy of patients with chronic lymphocytic leukemia (CLL). Novel treatment
      options for CLL include a new generation of purine analogs, antibodies and
      inhibitors of specific cell signaling pathways, which typically induce apoptosis
      or necrosis. A prospective analysis of patient blood samples revealed that a
      combination of four tests allowed the most appropriate and effective type of
      treatment to be selected prior to drug administration, and for the analysis of
      leukemic cell sensitivity to anticancer drug(s) during disease development. The
      comparative analysis of blood from the stable and progressive form of CLL in an
      individual patient revealed diversity in the response to anticancer agents. CLL
      peripheral blood mononuclear cells were incubated with cladribine + mafosfamide
      (CM), fludarabine + mafosfamide, CM + rituximab, rituximab alone (Rit) or kinetin
      riboside (RK). A combination of cell viability, differential scanning calorimetry
      (DSC) profiles of nuclear preparations and poly(ADP-ribose) polymerase 1 (PARP-1)
      protein expression analysis of the leukemic cells was performed to evaluate the
      anticancer effects of the tested agents during CLL development. The results of
      the present study indicate that such studies are effective in determining the
      most appropriate anticancer drug and could monitor disease progression on an
      individual level. In addition, the results of the current study suggest that CLL
      progression leads to diversification of the cellular drug response. The most
      efficient apoptosis inducer for the patient was purine analog RK when the disease
      was stable, while the CM combination was the most effective agent for the
      progressive form of disease.

PMID- 28454366
TI  - Gene signatures associated with drug resistance to irinotecan and oxaliplatin
      predict a poor prognosis in patients with colorectal cancer.
AB  - The identification of novel survival predictors may help to improve the
      appropriate management of colorectal cancer (CRC). In the present study, two gene
      sets associated with irinotecan or oxaliplatin resistance in CRC cell lines were
      first identified and subsequently applied to the clinical CRC microarray dataset
      GSE14333. Subsequently, a 60-gene irinotecan resistance-associated signature and
      a 13-gene oxaliplatin resistance-associated signature were established, which
      were able to classify CRC patients into high- and low-risk subgroups with varied
      clinical outcomes [irinotecan-resistance gene signature: hazard ratio
      (HR)=0.4607, 95% confidence interval (CI)=0.3369-0.6300, P<0.0001; oxaliplatin
      resistance gene signature: HR=0.6119, 95% CI=0.4547-0.8233, P=0.0008]. The
      performance of these two gene expression signatures in predicting outcome risk
      were also validated in two other independent CRC gene expression microarray
      datasets, GSE17536 (irinotecan-resistance gene signature: HR=0.5318, 95%
      CI=0.3359-0.8419, P=0.0079; oxaliplatin-resistance gene signature: HR=0.5383, 95%
      CI=0.3400-0.8521, P=0.0114) and GSE17537 (irinotecan-resistance gene signature:
      HR=0.2827, 95% CI=0.1173-0.6813, P=0.0088; oxaliplatin-resistance gene signature:
      HR=0.2378, 95% CI=0.09773-0.5784, P=0.0023). Furthermore, the combination of
      these two gene classifiers demonstrated a superior performance in CRC prognosis
      prediction than either used individually. Therefore, this study proposed novel
      gene classifier models for CRC prognosis prediction, which may be potentially
      useful to inform treatment decisions for patients with CRC in clinical settings.

PMID- 28454365
TI  - Downregulation of EGFR in a metastatic brain lesion of EGFR-mutated non-small
      cell lung cancer using a tyrosine kinase inhibitor: A case report.
AB  - Brain metastasis is a common complication in patients with cancer, with lung
      cancer being the most frequent origin of brain metastases. Epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have begun to serve a
      pivotal role in lung cancer treatment and have been reported to demonstrate
      anticancer activity against brain metastases by penetrating the blood-brain
      barrier. The present study reports, to the best of our knowledge, the first case
      of EGFR-mutated non-small cell lung cancer (NSCLC) brain metastasis that was
      surgically resected while the lesion was responding to the EGFR-TKI erlotinib.
      The results of the present study demonstrated that EGFR-mutated NSCLC cells were
      able to evade the cytotoxic effect of EGFR-TKI by downregulating EGFR expression,
      without exhibiting the T790M EGFR mutation.

PMID- 28454367
TI  - Matrix metalloproteinases in Vietnamese patients with colorectal cancer.
AB  - Matrix metalloproteinases (MMPs), a family of endopeptidases also known as
      gelatinases, have been reported to affect the acquisition of the cell
      proliferative, cell invasive and metastatic phenotype of several types of cancer.
      In particular, the gelatinases MMP-2 and -9 have been revealed to facilitate
      tumor growth and invasion in patients with colorectal cancer (CRC). However, it
      is not known whether the gelatinase activity of MMP-2 and -9 is also elevated in
      Vietnamese patients with CRC. The activity of MMP-2 and -9 in the tissue samples
      of 103 patients with CRC was evaluated by gelatin zymography and quantified using
      ImageJ. The association between the level of activity of MMP-2 and -9 and various
      clinicopathological factors was analyzed, and Chisio BioPAX Editor software was
      used to visualize the biological pathways regulating the activity of the MMPs.
      The present study noticed significantly increased activity of active MMP-2 and
      MMP-9 in tumor tissues (P<0.01), and significantly decreased levels of pro-form
      MMP-2 and MMP-9 in tumor tissues (P<0.01), compared with that in adjacent tissues
      in patients with CRC. A correlation between the normalized different activity of
      MMP-2 and -9 and various clinicopathological features was observed. Furthermore,
      bioinformatics analysis indicated that the alteration in the activity of MMP-2
      and MMP-9 may have been controlled by biological pathways involving the tissue
      inhibitors of metalloprotease-2 and -1. These findings indicate that the activity
      of the gelatinases MMP-2 and -9 affects the tumor progression and metastasis of
      patients with CRC, providing a potential novel approach for determining the
      prognosis of CRC.

PMID- 28454368
TI  - Anti-osteoclastic agent, denosumab, for a giant cell tumor of the bone with
      concurrent Paget's disease: A case report.
AB  - Paget's disease of the bone may predispose the development of malignant bone
      tumors such as osteosarcoma. Giant cell tumor (GCT) as a consequence of Paget's
      disease is rare. Bone GCT is characterized by rapid growth, the destruction of
      bone, extension to the surrounding soft tissue and abnormal bone turnover caused
      by an abnormality of the receptor activator of nuclear factor-kappaB (RANK)-RANK
      ligand (RANKL) pathway. Denosumab is a RANK-RANKL inhibitor, which is used to
      treat osteoporosis and bone GCT. In the current study, a 60-year-old male
      presented with severe pain located between the right thigh and the knee. The
      patient could not bear weight on the affected leg. The patient had suffered from
      Paget's disease for 15 years. The complications from Paget's disease included
      degenerative hip disease, for which the patient underwent a right total hip
      replacement. A right periacetabular lesion was identified and confirmed as
      Paget's disease-induced GCT by needle biopsy. A positron emission tomography
      (PET) scan revealed significant tumor metabolic activity. Subsequent to obtaining
      informed consent, the patient started treatment with denosumab. A total of 2.5
      months after starting denosumab, a PET scan showed no residual pathological
      uptake at the site of the previously identified large PET avid tumor. After 1
      year, the patient exhibited a satisfactory clinical improvement. In conclusion,
      treatment with denosumab markedly reduced the size of the hemi-pelvic GCT and led
      to a complete metabolic response.

PMID- 28454369
TI  - Overexpression of erythropoietin-producing hepatocyte receptor B4 and ephrin-B2
      is associated with estrogen receptor expression in endometrial adenocarcinoma.
AB  - Endometrial adenocarcinoma (EC) is one of the most frequently diagnosed types of
      endometrial cancer and is typically a consequence of continuous estrogen receptor
      stimulation. Erythropoietin-producing hepatocyte receptor B4 (EphB4) and its
      ligand ephrin-B2 have been reported to be overexpressed in EC cells; however, the
      function in EC remains unclear. The present study aimed to elucidate the role of
      EphB4 and ephrin-B2 in EC. The protein expression pattern of EphB4 and ephrin-B2
      was analyzed through immunohistochemistry and western blot analysis in
      endometrium with adenomyosis or simple endometrial hyperplasia, atypical
      endometrial hyperplasia, double-positive estrogen receptor (ER)/progesterone
      receptor (PR) EC and double-negative ER/PR EC. The expression of EphB4 and ephrin
      B2 was demonstrated to be increased in atypical EH and ER/PR-positive EC, but not
      ER/PR-negative EC. Furthermore, EphB4 and ephrin-B2 expression was positively
      associated with ER expression in EC tissue. The results of the present study
      suggest that the overexpression of EphB4 and ephrin-B2 in the endometrium serves
      a role in the pathogenesis of EC, in addition to being associated with ER
      expression.

PMID- 28454370
TI  - Methylation of CDKN2B CpG islands is associated with upregulated telomerase
      activity in children with acute lymphoblastic leukemia.
AB  - The aim of the present study was to investigate the association between
      methylation of cyclin-dependent kinase inhibitor 2B (CDKN2B) CpG islands and
      telomerase activity in children with acute lymphoblastic leukemia (ALL). A total
      of 72 children with ALL and 12 children with immune thrombocytopenia (ITP) were
      subjected to bone marrow aspiration and methylation-specific polymerase chain
      reaction analysis, and modified telomeric repeat amplification protocol assay
      analyses, to evaluate CDKN2B methylation and telomerase activity, respectively.
      The results of the present study demonstrated that, of these 72 children with
      ALL, 31 exhibited CDKN2B methylation at diagnosis (43.1%), whereas 41 exhibited
      no CDKN2B methylation (36.9%). However, no CDKN2B methylation was detected in the
      ITP controls. Furthermore, the mean level of telomerase activity was 39.52+/
      39.33 total product generated (TPG) units in children with ALL, which was
      significantly increased compared with 2.49+/-2.27 TPG units in the ITP controls
      (P=0.002). The mean levels of telomerase were 49.09+/-44.43 and 29.99+/-32.43 TPG
      units in children with ALL with and without CDKN2B methylation, respectively
      (P=0.041), therefore children with ALL exhibited significantly increased levels
      of telomerase. The increased telomerase activity was significantly associated
      with increased risk of childhood ALL (P=0.023). A total of 22/31 children with
      ALL with methylated CDKN2B (71.0%) and 17/41 children with ALL with unmethylated
      CDKN2B (41.46%) exhibited increased telomerase activity (>15 TPG units). The
      results of the present study suggest that hypermethylation of CDKN2B CpG islands
      and hyperactivity of telomerase are common events in childhood ALL, and
      hypermethylation of CDKN2B CpG islands was significantly associated with
      upregulated telomerase activity (P=0.013).

PMID- 28454371
TI  - Synergistic effects of a novel lipid-soluble extract from Pinellia pedatisecta
      Schott and cisplatin on human cervical carcinoma cell lines through the
      regulation of DNA damage response signaling pathway.
AB  - Herbal medicines have been recognized as an attractive approach for cancer
      therapy with minimal side effects. The present study investigated the type of
      interaction between a novel lipid-soluble extract from Pinellia pedatisecta
      Schott (PE) and cisplatin (CDDP) on human cervical cancer SiHa and CaSki cell
      lines in vitro. The mechanism of this combination was studied using cell
      proliferation, invasion and apoptosis assays, and by analyzing cell cycle
      distribution and protein expression, with a focus on DNA damage response (DDR)
      activation. Equipotent combinations of PE and CDDP were determined by isobologram
      analysis, in order to evaluate potential synergy. The combination index for SiHa
      cells was 0.43, and the index for CaSki cells was 0.68, indicating synergy.
      Treatment with PE and CDDP combined resulted in a significantly greater
      inhibition of invasion in the two cells, compared with either drug alone (SiHa,
      P<0.01; CaSki, P<0.001). This co-treatment induced significantly more apoptosis
      in the two cell lines, and arrested cells at the G0/G1 phase and G2/M phase in
      SiHa and CaSki, respectively, with a significant decrease (P<0.01) in S phase
      cells in the two cell lines. Combined PE and CDDP targeting synergistically
      enhanced the expression of markers of DDR (phosphorylation of ataxia
      telangiectasia mutated, checkpoint kinase (Chk)-1, Chk-2, and gamma-H2A histone
      family member X) in cells. These results suggest that PE and cisplatin act
      synergistically in cervical cancer cells with high DDR activation. The approach
      presented in the present study may have important implications for the
      pharmacological mechanism of Pinellia pedatisecta Schott and cervical cancer
      therapeutic strategies.

PMID- 28454372
TI  - Distinguishing between intramural pregnancy and choriocarcinoma: A case report.
AB  - Intramural pregnancy is a rare type of ectopic pregnancy with an unclear
      etiology. It may be associated with uterine wall injury and/or abnormal uterine
      conditions, such as adenomyosis, in certain cases. In the present report, a case
      of intramural pregnancy associated with adenomyosis is discussed. The patient was
      34 years old and presented with amenorrhea for 40 days. Ultrasonography and
      magnetic resonance imaging revealed a mixed echogenic mass located within the
      posterior wall of the uterine fundus with abundant blood flow. In addition, the
      patient's beta-human chorionic gonadotropin levels were markedly elevated;
      however, these levels demonstrated a declining tendency. Clinically, it was
      difficult to distinguish the diagnosis of the case between intramural pregnancy
      and choriocarcinoma. Following initial treatment with methotrexate-based
      chemotherapy, a laparotomy was performed to confirm the diagnosis and excise the
      lesion. Pathological analysis confirmed a diagnosis of intramural pregnancy and
      adenomyosis within the uterine wall. The results of the present case report
      suggest that surgical intervention should be the first action performed when
      intramural pregnancy is suspected, in order to confirm the diagnosis and treat
      the disease.

PMID- 28454373
TI  - Inhibition of CYFIP2 promotes gastric cancer cell proliferation and
      chemoresistance to 5-fluorouracil through activation of the Akt signaling
      pathway.
AB  - Gastric cancer is a common gastrointestinal malignancy that accounts for a
      notable proportion of cancer-associated mortalities worldwide. Cytoplasmic
      fragile X mental retardation 1-interacting protein 2 (CYFIP2) is a novel p53
      mediated pro-apoptotic protein whose expression is decreased in gastric cancer.
      However, whether decreased expression of CYFIP2 contributes to gastric
      carcinogenesis remains unclear. In order to mimic in vivo gastric tumor CYFIP2
      expression levels, the present study used short hairpin RNA targeting CYFIP2 mRNA
      to silence CYFIP2 expression in MGC803 and SGC7901 gastric cancer cells. Gastric
      cancer cells with constitutively decreased CYFIP2 expression levels were
      successfully established. It was observed that CYFIP2 knockdown promoted
      proliferation and colony formation, and inhibited apoptosis in these cells.
      Furthermore, 5-fluorouracil (5-FU)-induced apoptosis was decreased following
      inhibition of CYFIP2 expression. In SGC7901 cells, protein expression of active
      caspase-3 and cleaved poly (ADP-ribose) polymerase was increased following
      treatment with 5-FU, while phosphorylated Akt serine/threonine kinase 1 (Akt)
      levels were decreased. These 5-FU-induced effects were reduced following CYFIP2
      knockdown. In addition, inhibition of the Akt signaling pathway using the Akt
      inhibitor LY294002 restored CYFIP2-knockdown SGC7901 cell chemosensitivity to 5
      FU. The results of the present study demonstrate that decreased CYFIP2 expression
      is associated with increased gastric tumor growth in vitro and that CYFIP2
      knockdown-induced activation of the Akt pro-survival signaling pathway confers
      resistance to 5-FU-based chemotherapy in gastric cancer cells. Therefore,
      combined treatment with an Akt inhibitor and chemotherapeutic drugs may improve
      the efficacy of gastric cancer therapy in patients with low CYFIP2 expression.

PMID- 28454374
TI  - Arsenic trioxide inhibits tumor-induced myeloid-derived suppressor cells and
      enhances T-cell activity.
AB  - Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of the
      immunosuppressive network, are associated with immune suppression and considered
      a prime target for cancer immunotherapy. At present, various strategies have been
      explored to deplete and/or inactivate MDSCs in vivo. In this study, we
      investigated the effect of arsenic trioxide (ATO) on MDSCs derived from tumor
      bearing mice. This study examined the in vitro and in vivo effects of ATO
      administration on MDSCs from C57/j mice bearing either the B16 or H22 tumor. The
      MDSCs were then characterized for phenotype, gene expression and function.
      Administration with ATO in vitro significantly induced MDSC differentiation,
      inhibited their proliferation and triggered apoptosis. Treatment with ATO in
      these murine tumor models significantly inhibited tumor growth and splenomegaly,
      decreased the percentages of MDSCs in the spleen, promoted their differentiation,
      reduced tumor necrosis factor-alpha and interleukin-10 levels and weakened the
      immune inhibition activity of MDSCs on T cells. In addition, we observed the
      underlying mechanism involved in the regulation of MDSCs by ATO, which included a
      panel of cytokines and signaling pathways. The findings showed the
      immunoregulatory effects of ATO by inducing apoptosis, promoting differentiation
      and inhibiting the function of MDSCs, suggesting that ATO has potential clinical
      benefit as it selectively attenuates MDSC-induced immunosuppression.

PMID- 28454375
TI  - A comprehensive analysis of cancer-driving mutations and genes in kidney cancer.
AB  - An accumulation of driver mutations is important for cancer formation and
      progression, and leads to the disruption of genes and signaling pathways. The
      identification of driver mutations and genes has been the subject of numerous
      previous studies. The present study was performed to identify cancer-driving
      mutations and genes in renal cell carcinoma (RCC), prioritizing noncoding
      variants with a high functional impact, in order to analyze the most informative
      features. Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping
      version 2 (Polyphen2) and MutationAssessor were applied to predict deleterious
      mutations in the coding genome. OncodriveFM and OncodriveCLUST were used to
      detect potential driver genes and signaling pathways. The functional impact of
      noncoding variants was evaluated using Combined Annotation Dependent Depletion,
      FunSeq2 and Genome-Wide Annotation of Variants. Noncoding features were analyzed
      with respect to their enrichment of high-scoring variants. A total of 1,327
      coding mutations in clear cell RCC, 258 in chromophobe RCC and 1,186 in papillary
      RCC were predicted to be deleterious by all three of MutationAssessor, Polyphen2
      and SIFT. In total, 77 genes were positively selected by OncodriveFM and 1 by
      OncodriveCLUST, 45 of which were recurrently mutated genes. In addition, 10
      signaling pathways were recurrently mutated and had a high functional impact bias
      (FM bias), and 31 novel signaling pathways with high FM bias were identified.
      Furthermore, noncoding regulatory features and conserved regions contained
      numerous high-scoring variants, and expression, replication time, GC content and
      recombination rate were positively correlated with the densities of high-scoring
      variants. In conclusion, the present study identified a list of cancer-driving
      genes and signaling pathways, features like regulatory elements, conserved
      regions, replication time, expression, GC content and recombination rate are
      major factors that affect the distribution of high-scoring non-coding mutations
      in kidney cancer.

PMID- 28454376
TI  - Expression and function of MutT homolog 1 in distinct subtypes of breast cancer.
AB  - Human MutT homolog 1 (MTH1) detoxifies the oxidized DNA precursor 8-oxo-2'
      deoxyguanosine-5'-triphosphate and serves a tumor suppressive role in distinct
      types of cancer. In the present study, the expression of MTH1 was examined in
      various subtypes of breast cancer, and the effect of its suppression on breast
      cancer growth was characterized in vitro and in vivo. MTH1 mRNA and protein
      levels were assessed using the reverse transcription-quantitative polymerase
      chain reaction and immunohistochemistry. The effect of MTH1 expression on the
      proliferation of breast cancer cells was investigated in vitro using Cell
      Counting Kit-8 and colony formation assays, and in vivo using breast cancer cell
      line xenografts in mice. The toxicity of the MTH1 inhibitor TH588 was
      investigated in nude mice. A marked increase in MTH1 protein and mRNA levels was
      demonstrated in breast cancer tissues compared with the non-cancerous control.
      However, no apparent differences in MTH1 expression were observed between
      distinct molecular subtypes of breast cancer. MTH1 overexpression was
      demonstrated to be independent of patient age, tumor size and lymph node
      metastasis. Inhibition of MTH1 decreased cancer cell viability and the clonogenic
      potential of cancer cells in a dose-dependent manner. These results were
      confirmed by decreased in vivo proliferation of MCF7, MDA-MB-231 and MDA-MB-453
      cancer cell lines, representing distinct subtypes of breast cancer. Although
      inhibition of MTH1 activity decreased xenograft growth in mice, no major adverse
      effects of TH588 were detected on the basis of blood biochemistry, and liver and
      kidney function. The results of the present study suggested that MTH1 is
      overexpressed in the majority of breast cancers, independent of the molecular
      identity and clinicopathological features of the tumor, including patient age,
      tumor size and lymph node metastasis. Inhibition of MTH1 activity suppressed the
      growth of three subtypes of breast cancer, including luminal, basal-like and
      human epidermal growth factor receptor 2-positive, in vitro and in vivo.
      Treatment with the MTH1 inhibitor appears to be safe; however, further studies
      are required prior to the clinical use of MTH1 inhibitors.

PMID- 28454377
TI  - Frequent expression of human leukocyte antigen class I and the status of
      intratumoral immune cells in alveolar soft part sarcoma.
AB  - The prognosis of alveolar soft part sarcoma is poor, despite the slow growth of
      the tumor. A number of cases with spontaneous regression of this rare tumor have
      been reported. Although the mechanisms underlying spontaneous regression remain
      uncertain, local immune reaction may be a possible contributing factor.
      Immunohistochemical expression of human leukocyte antigen (HLA) class I, cluster
      of differentiation (CD) 3, CD4, CD8, CD20, CD45, CD56, CD68, CD138 and CD163 were
      assessed in a series of 10 alveolar soft part sarcomas, and the expression
      profiles were associated with patients' clinicopathological parameters.
      Expression of HLA class I was observed in almost all the tumor cells of all
      cases. CD8(+) cells were identified in all tumors with varying densities.
      Moderate infiltration of CD8(+) cells was detected in three patients; one of
      these patients survived with long-term tumor remission. Infiltration of CD10(+),
      CD20(+), CD56(+) or CD138(+) cells was not revealed in all tumors. Moderate
      diffuse infiltration of CD163(+) cells was observed in all tumors. To the best of
      our knowledge, the present study represents the first report of intratumoral
      immune cells in alveolar soft part sarcoma. Frequent expression of HLA class I in
      tumor cells was observed. CD8(+) cells were identified at various densities and
      CD163(+) cells were observed in alveolar soft part sarcoma. Moderate infiltration
      of CD8(+) cells in patients with a good prognosis may indicate the antitumor
      effects of immune cells in alveolar soft part sarcoma.

PMID- 28454378
TI  - Prognostic value of intratumoral carbonic anhydrase IX expression in testicular
      germ cell tumors.
AB  - Testicular germ cell tumors (TGCTs) represent a highly curable malignancy,
      however a small proportion of patients fails to be cured with cisplatin-based
      chemotherapy. Carbonic anhydrase IX (CA IX) is upregulated by hypoxia in several
      cancer types and correlates with a poor prognosis. The present translational
      study evaluated expression and prognostic value of CA IX in TGCTs. Surgical
      specimens from 228 patients with TGCTs were processed by the tissue microarray
      method and subjected to immunohistochemistry with the M75 monoclonal antibody. CA
      IX expression was evaluated in tumors vs. adjacent normal testicular tissues and
      correlated with clinicopathological characteristics and clinical outcome. CA IX
      expression was detected in 62 (30.2%) of TGCTs compared to 0 (0%) of normal
      tissue adjacent to testicular tumor (P<0.001). The highest frequency of the CA IX
      expression was detected in teratoma (39.0%), followed by seminoma (22.7%), yolk
      sac tumor (22.2%), embryonal carcinoma (11.9%) and choriocarcinoma (7.7%). None
      of germ cell neoplasias in situ (GCNIS) exhibited CA IX expression. Patients
      without the CA IX tumor expression showed significantly better progression-free
      survival, but not overall survival, compared to patients with the CA IX
      expression [hazard ratio (HR), 0.57; 95% CI, 0.32-1.02; P=0.037 and HR, 0.58; 95%
      CI, 0.29-1.16; P=0.088, respectively]. There was no significant correlation
      between the CA IX expression and clinicopathological variables. The intratumoral
      CA IX expression can serve as a prognostic marker in the TGCT patients. These
      results suggest that activation of the hypoxia-induced pathways may be important
      in the treatment failure in TGCTs patients.

PMID- 28454379
TI  - Characterization of single lesion nonfunctioning pancreatic neuroendocrine
      carcinoma via computed tomography.
AB  - Nonfunctioning pancreatic neuroendocrine carcinoma (NPNEC) is a poorly
      differentiated neuroendocrine carcinoma and a rare type of pancreatic cancer.
      Computed tomography (CT)-based imaging is currently the most effective method for
      diagnosing and classifying NPNEC. The present study investigated the clinical
      features and CT manifestations of this disease. The CT manifestations and
      clinical data of 13 patients with NPNEC, confirmed by surgery or needle biopsy,
      were retrospectively analyzed. None of the 13 patients exhibited endocrine
      related symptoms and a single lesion with a variable position in the pancreatic
      was observed in all patients. The tumors were generally round or irregular, with
      inhomogeneous density and an average diameter of 7.45+/-3.92 cm (range, 4.0-16.0
      cm). Cystic necrosis zones were observed in 5 patients and calcification was
      observed in 2. A total of 4 patients exhibited intrahepatic metastases, and 2
      patients demonstrated spleen and colon invasion. Enhanced scanning indicated that
      tumors were markedly enhanced. There were 11 cases of middle or high-grade
      enhancement (84.6%) and 2 cases of mild enhancement (15.4%). Marked envelope
      enhancement was observed in 3/11 patients with high-grade enhancement. In
      conclusion, the majority of patients with NPNEC lacked characteristic
      manifestations. While the CT examination revealed certain characteristics,
      histological analysis was necessary to confirm diagnoses.

PMID- 28454380
TI  - miR-150 is downregulated in osteosarcoma and suppresses cell proliferation,
      migration and invasion by targeting ROCK1.
AB  - Osteosarcoma (OS) is the most common form of bone malignancy in children and
      adolescents. A class of molecules known as microRNAs (miRNAs) have been routinely
      associated in the development and progression of OS. The present study was
      centered on the less well-known miRNA, miRNA (miR)-150, and its role in OS was
      investigated. The levels of miR-150 were examined in 40 tissue specimens from
      patients with OS and adjacent normal tissues using reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) analysis. In addition the
      expression levels of miR-150 were examined in three OS cell lines and a normal
      osteoblast cell line. Cell proliferation, migration and invasion assays were
      performed to establish the correlation between miR-150 and metastasis. The
      potential targets of miR-150 were theoretically predicted and one high-scoring
      target, Rho-associated kinase 1 (ROCK1), was established to be a direct target
      using RT-qPCR and western blot analyses and Pearson's correlation analysis. The
      results indicated that miR-150 was downregulated in tissues from patients with OS
      and cell lines. Secondly, it was shown that the overexpression of miR-150 was
      inversely correlated with OS cell proliferation, migration and invasion. It was
      also shown that miR-150 negatively regulated the gene expression of ROCK1 in the
      OS cell lines. Finally, the interaction between miR-150 and ROCK1 was established
      and it was shown that miR-150 directly targeted ROCK1. In conclusion, miR-150 was
      found to be a tumor suppressor, and the suppression of miR-150 resulted in
      elevation in the levels of ROCK1. This interaction between miR-150 and ROCK1 may
      be key in the progression of OS. Furthermore, miR-150 or ROCK1 may be potential
      therapeutic targets for the treatment of OS.

PMID- 28454381
TI  - Optimized construction of MUC1-VNTRn DNA vaccine and its anti-pancreatic cancer
      efficacy.
AB  - Considering mucin 1-variable number tandem repeat (MUC1-VNTRn) as a novel target
      for pancreatic cancer immunotherapy, the present study aimed to screen and
      identify the pVAX1-MUC1-VNTRn DNA vaccine with the strongest immunogenicity.
      Following construction of a pVAX1-MUC1-VNTRn plasmid, immature dendritic cells
      (DCs) were subjected to transfection, and mature DCs were then co-cultured with
      autologous T-cells. The numbers of cytotoxic T lymphocytes (CTLs) secreting
      interferon (IFN)-gamma were determined using an enzyme-linked immunospot assay,
      and CytoTox(r) was also used to examine the MUC1-VNTRn-specific Lethal effect of
      CTLs on Capan2 cells. Additional in vivo experiments in mice were performed to
      confirm the antitumor effect of the DNA vaccine candidate. The present study
      successfully constructed the pVAX1-MUC1-VNTRn plasmid, which expresses the target
      protein in eukaryotic cells. Additionally, upon uptake of the pVAX1-MUC1-VNTRn
      plasmid, the immature DCs differentiated into mature DCs. The levels of the DC
      surface molecules cluster of differentiation (CD) 80, CD86, human leukocyte
      antigen-antigen D related, interleukin (IL)-12, IL-17 and IFN-gamma were
      significantly higher, while the levels of IL-10 and IL-14 were lower, in mature
      DCs of the stimulated groups compared with the immature DCs of the non-stimulated
      groups (all P<0.01). In addition, the MUC1-VNTR6 and MUC1-VNTR9 groups, in which
      DCs were capable of activating autologous T-cells, showed increased IFN-gamma
      producing T-cells compared with the other groups (strong MUC1-VNTR1, weak VNTR1,
      VNTR3, VNTR4 and MUC1-cDNA groups; all P<0.001). In addition, the Lethal effect
      of CTLs on Capan2 cells in these two groups was stronger compared with the other
      groups (all P<0.001). Furthermore, the induced protective and therapeutic immune
      responses in mouse experiments showed that the pVAX1-MUC1-VNTR6DNA vaccine likely
      possessed the strongest immunogenicity, and its ability to inhibit panc02-MUC1
      tumor growth was superior to other DNA vaccines (P<0.01). The present study
      provides compelling evidence that pVAX1-MUC1-VNTRn has the potential to express
      the target protein in eukaryotic cells, and thatpVAX1-MUC1-VNTR6 was
      characterized by the strongest Lethal effect in both in vivo and in vitro
      experiments.

PMID- 28454382
TI  - Increased B7-H4 expression during esophageal squamous cell carcinogenesis is
      associated with IL-6/STAT3 signaling pathway activation in mice.
AB  - B7-homolog 4 (B7-H4), one of the costimulatory molecules of the B7 family, has
      been reported to be widely expressed in multiple types of cancer tissues, and to
      be important in tumor progression and poor prognosis. However, the role of B7-H4
      in esophageal precancerous lesions has not been elucidated yet. In the present
      study, a model of esophageal squamous cell carcinogenesis was established in 208
      C57BL/6 mice by 4-nitroquinoline-1-oxide (4NQO) drinking water of mice, and the
      changes in the expression of B7-H4 during the whole pathological process were
      investigated. Hematoxylin and eosin staining results demonstrated that the
      pathological stage was exacerbated with the increase in time of 4NQO-mediated
      carcinogenesis induction, and the pathological features were similar to those
      observed in humans. Immunohistochemistry results revealed that B7-H4 expression
      was upregulated and positively correlated with pathological stage (P<0.0001) as
      well as with infiltration of cluster of differentiation (CD) 11b+ macrophage
      cells (P=0.0002). In addition, B7-H4 messenger RNA expression increased in the
      esophagi of model mice compared with that of control mice, which was positively
      associated with the gene expression of interleukin (IL)-6 and signal transducer
      and activator of transcription 3 (STAT3), according to the results of reverse
      transcription-quantitative polymerase chain reaction analysis. Similarly, B7-H4
      protein expression was upregulated in the esophageal tissues of model mice in
      comparison with that of control mice, and was positively associated with IL-6
      expression and STAT3 phosphorylation. In conclusion, the present data suggested
      that B7-H4 expression increased during esophageal squamous cell carcinogenesis in
      mice in association with IL-6/STAT3 signaling pathway activation.

PMID- 28454383
TI  - FAM53B truncation caused by t(10;19)(q26;q13) chromosome translocation in acute
      lymphoblastic leukemia.
AB  - RNA-sequencing of the patient's bone marrow detected fusion transcripts in which
      the coding sequence of the FAM53B gene (from 10q26) was fused to a genomic
      sequence (from 19q13) that mapped upstream of the SLC7A10 locus. Reverse
      transcription-polymerase chain reaction together with Sanger sequencing verified
      the presence of this fusion transcript. The FAM53B fusion transcript is not
      expected to produce any chimeric protein. However, it may code for a truncated
      FAM53B protein consisting of the first 302 amino acids of FAM53B together with
      amino acids from the 19q13 sequence. Functionally, the truncated FAM53B would be
      similar to the protein encoded by the FAM53B sequence with accession no.
      BC031654.1 (FAM53B protein accession no. AAH31654.1). Furthermore, the truncated
      protein contains the entire conserved domain of the FAM53 protein family. The
      chromosome aberration t(10;19)(q26;q13) detected in this study was previously
      reported in a single case of ALL, in which it was also the sole karyotypic
      change. Both patients entered complete hematological and cytogenetic remission
      following treatment.

PMID- 28454384
TI  - New applications of the acridine orange fluorescence staining method: Screening
      for circulating tumor cells.
AB  - The aim of the present study was to explore use of the acridine orange
      fluorescence (AO-F) staining method for screening of circulating tumor cells
      (CTCs) in renal cell carcinoma (RCC) patients. The AO-F positive staining rate of
      live and dead tumor cells was calculated. The positive staining rate in the live
      group was 93.4+/-3.0%, while the dead group failed to emit specific fluorescence.
      A known number of tumor cells were added to peripheral blood, and the detection
      sensitivity of the four groups (50, 100, 200 and 500 cells/tube) was 10.2+/-3.8,
      9.2+/-2.3, 10.8+/-2.6 and 10.5+/-1.9%, respectively. The average detection
      sensitivity of the four groups was 10.16+/-2.73%. There was a positive
      correlation between the number of cells that was positively stained with AO-F and
      the total number cells in the system (chi2=0.959; P<0.001). Subsequently, the AO
      F staining method was used to detect positive staining cells in 8 healthy
      volunteers (control group), and 112 non-metastatic and 27 metastatic RCC
      patients. The positive staining rate was 13.67% (19/139) in RCC patients, while
      none of the control group was positive. The AO-F positive staining rate was not
      significantly different between the metastatic and non-metastatic patients
      according to age, gender, the pathological pattern, T2/3 (according to the Tumor
      Node-Metastasis classification) or Fuhrman grade, while there was a significant
      difference according to T1. The positive staining rate was 8.93% (10/112) for non
      metastatic patients and 33.33% (9/27) for metastatic patients, which showed a
      significant difference (P<0.05). In 112 non-metastatic and 27 metastatic
      patients, the positive staining rate was not significantly associated with
      gender, age, tumor size, the pathological pattern, T classification, Fuhrman
      grade, the presence of a lesion or metastasis to the lungs. The present study
      demonstrated that the method of CTC staining with AO-F, which has high
      reproducibility and specificity, was feasible for identifying CTCs and warrants
      further study.

PMID- 28454385
TI  - Neuroendocrine differentiation is predictive of poor survival in patients with
      stage II colorectal cancer.
AB  - The diagnosis of neuroendocrine differentiation (NED) is made primarily on the
      basis of ultrastructure and/or immunohistochemistry (IHC). Synaptophysin (Syn)
      and chromogranin A (CgA) are two important frequently used NED markers in
      colorectal cancer (CRC). The association between NED and the prognosis of stage
      II CRC remains controversial. Administration of adjuvant chemotherapy remains
      challenging for stage II CRC. Identification of reliable factors that improve the
      selection of patients with stage II CRC at high risk following surgery is of
      great importance. A total of 151 cases of patients with stage II CRC who received
      radical surgery in The Second Affiliated Hospital of Zhejiang University
      (Hangzhou, China) between January 2002 and March 2011 were assayed for Syn and
      CgA using IHC, following which patients were classified as NED(+) or NED(-).
      Survival curves were constructed using the Kaplan-Meier estimator, and the
      prognostic value was determined using a log-rank test and Cox's regression test.
      In the 151 cases of stage II CRC examined, the incidence of NED was 34.44%. The
      overall survival of the NED(+) group was significantly less favorable than that
      of the NED(-) group (P=0.001). The 5-year survival rate was 68% for NED(+) (n=51)
      and 90% for NED(-) (n=97). The independent prognostic factors of survival of
      patients with stage II CRC following multivariate analysis were age >=65 years
      (P=0.007) and NED-positivity (P=0.014). NED was revealed to be an independent
      factor of poor prognosis for patients with stage II CRC, which may offer
      potential for improved therapy stratification.

PMID- 28454386
TI  - Decreased calpain 6 expression is associated with tumorigenesis and poor
      prognosis in HNSCC.
AB  - Calpains are a family of intracellular cysteine proteases involved in various
      biological processes. Previously, the family was identified to have abnormal
      expression in several types of malignant tumor. Calpain 6 was less well known;
      however, it was recently identified to be involved in the carcinogenesis of
      certain types of malignant tumor. However, the expression of calpain 6 in head
      and neck squamous cell carcinoma (HNSCC) remains unclear. A total of six datasets
      from the Gene Expression Omnibus (GEO) was analyzed and an association between
      calpain 6 expression levels and HNSCC was identified, with the expression of
      calpain 6 observed to be significantly decreased in HNSCC (P<0.01). However, the
      expression of calpain 6 may vary between distinct tumor stages of HNSCC.
      Furthermore, calpain 6 expression was positively associated with the survival
      rate in patients with HNSCC (P<0.05), with increased expression of calpain 6
      associated with an improved survival outcome. Calpain 6 expression was analyzed
      using an HNSCC tissue microarray and these results were consistent with the
      statistical analysis of the bioinformatics data from the GEO, indicating that
      calpain 6 may be a tumor suppressor protein in HNSCC.

PMID- 28454387
TI  - Association between Wnt inhibitory factor 1 and receptor tyrosine kinase-like
      orphan receptor 2 protein expression and the clinical pathological significance
      in benign and malignant pancreatic lesions.
AB  - Pancreatic cancer is one of the most malignant types of tumor. It is important to
      elucidate the underlying molecular mechanisms of pancreatic tumorigenesis and to
      identify novel biomarkers as therapeutic targets of pancreatic cancer. In the
      present study, the protein expression levels of Wnt inhibitory factor 1 (WIF1)
      and receptor tyrosine kinase-like orphan receptor 2 (ROR2) were examined in a
      collection of pancreatic ductal carcinoma and benign pancreatic lesion tissue
      samples using immunohistochemistry. The positive expression rate of WIF1 protein
      in pancreatic ductal carcinoma was demonstrated to be significantly decreased
      compared with that of the paracancerous tissue, benign lesions and wild-type
      pancreatic tissue (P=0.002, P<0.0001, P=0.001, respectively). The positive
      expression rate of ROR2 protein in pancreatic ductal carcinoma was demonstrated
      to be significantly increased compared with that of the paracancerous tissue,
      benign lesions and wild-type pancreatic tissue (P<0.0001). There was a negative
      association between WIF1 and ROR2 expression in the pancreatic ductal carcinoma
      samples (P=0.004). The survival period of patients with negative WIF1 and
      positive ROR2 protein expression was demonstrated to be significantly decreased
      compared with that of patients with positive WIF1 and negative ROR2 protein
      expression (P<0.0001). The expression levels of WIF1 and ROR2 protein reflected
      the incidence, development, clinical and biological behavior, and prognosis of
      pancreatic ductal carcinoma. Patients with negative WIF1 and positive ROR2
      protein expression had poor prognosis. The results indicate that WIF1 and ROR2
      are important biomarkers in pancreatic cancer.

PMID- 28454388
TI  - CXCR4 knockdown inhibits the growth and invasion of nasopharyngeal cancer stem
      cells.
AB  - Nasopharyngeal cancer is a type of malignant tumor with a high rate of incidence.
      Cancer stem cells are regarded as one of the main causes for the formation and
      recurrence of nasopharyngeal cancer. CXC chemokine receptor type 4 (CXCR4) has
      been reported to perform an important role in cancer; however, the association
      between CXCR4 and nasopharyngeal cancer stem cells remains unclear. The present
      study explored the effect of CXCR4 on cellular viability, apoptosis and invasion
      of nasopharyngeal cancer stem cells. Results of the present study demonstrated
      that knockdown of CXCR4 inhibited the viability and invasion of nasopharyngeal
      cancer stem cells and promoted cellular apoptosis. Further studies have revealed
      that the anti-tumor effect of CXCR4 knockdown was associated with the inhibition
      of the protein kinase B signal. These results demonstrate that the knockdown of
      CXCR4 resulted in an anti-tumor effect in nasopharyngeal cancer stem cells.
      Therefore, CXCR4 may become a promising therapeutic target in the treatment of
      nasopharyngeal cancer.

PMID- 28454389
TI  - Notch signaling is important for epithelial-mesenchymal transition induced by low
      concentrations of doxorubicin in osteosarcoma cell lines.
AB  - Osteosarcoma is an aggressive pediatric tumor affecting growing bones that
      typically occurs in adolescents and young adults. Although advances in treatment
      have been made in recent years, a high proportion of patients relapse due to
      metastases, which are frequently resistant to chemotherapy and pose a significant
      threat to long-term survival. Previous studies have demonstrated that the
      epithelial-mesenchymal transition (EMT) is associated with cancer occurrence and
      metastasis, and our previous study demonstrated the occurrence of EMT in
      osteosarcoma. Notch is a regulator involved in several cellular processes, and
      previous studies have identified that the Notch signaling pathway may be
      activated during chemotherapy. However, whether chemotherapy affects the EMT
      remains to be elucidated. To address this issue, in the present study
      osteosarcoma cells were exposed to sublethal doses of doxorubicin, which resulted
      in upregulation of the expression of genes in the Notch signaling pathway and its
      target genes. Furthermore, doxorubicin treatment promoted mesenchymal-like
      properties and enhanced the migration and invasion of cells. In addition,
      treatment with the selective gamma-secretase inhibitor DAPT was able to prevent
      the EMT and inhibit the in vitro migration of osteosarcoma cells. The results of
      this study suggested that there is a significant correlation between the Notch
      signaling pathway and the EMT, and revealed an underlying molecular mechanism by
      which doxorubicin may induce the EMT via Notch signaling.

PMID- 28454390
TI  - Expression of novel cancer/testis antigen TMEM31 increases during metastatic
      melanoma progression.
AB  - Cancer/testis (CT) antigens are promising targets for immunotherapy due to their
      restricted expression in the germ cells of the testis in healthy tissue and high
      immunogenicity. The aim of the present study was to determine whether
      transmembrane protein 31 (TMEM31) is a CT antigen and to investigate the pattern
      of TMEM31 expression during the progression of melanoma. The pattern of
      expression of human TMEM31 mRNA in multiple human tissues was determined through
      reverse transcription-polymerase chain reaction analysis. TMEM31 protein
      expression was analyzed in the human testis, in addition to 128 primary melanoma
      and 64 metastatic melanoma samples through immunohistochemistry analysis. TMEM31
      was identified to be predominantly expressed in the testis and weakly expressed
      in the placenta. In addition, TMEM31 protein expression was detected in 120/190
      (63.16%) melanoma samples (primary and metastatic). The intensity of TMEM31
      staining in metastatic and primary melanomas was determined through
      semiquantitative integrated optical density (IOD) analysis, and identified to be
      significantly increased in metastatic melanoma compared with primary melanoma
      (0.24+/-0.03 vs. 0.09+/-0.01 IOD/area; P<0.001). The expression of TMEM31 protein
      was significantly increased in metastatic compared with primary melanoma samples
      (76.56 vs. 56.35%; P=0.017). The results of the present study suggest that TMEM31
      is a novel CT antigen that serves an essential role in melanoma metastasis, in
      addition to being a potential immunotherapeutic target for the treatment of
      patients with melanoma.

PMID- 28454391
TI  - Upregulation of KIN17 is associated with non-small cell lung cancer invasiveness.
AB  - Kin17 DNA and RNA binding protein (Kin17) is a highly conserved protein that
      participates in DNA replication, DNA repair and cell cycle progression. Recently,
      the tumor-promoting function of Kin17 has been demonstrated and increasingly
      studied. In the present study, the role of Kin17 in the invasion and metastasis
      of non-small cells lung cancer (NSCLC) was investigated. Elevated Kin17 mRNA and
      protein expression was identified in a total of 97 NSCLC and benign lung lesion
      tissue specimens. Kin17 overexpression was significantly correlated with high
      tumor grade and lymph node metastasis, indicating poor patient prognosis. Scratch
      and Transwell assays demonstrated that the knockdown of KIN17 inhibited the
      ability of NSCLC cells to migrate and invade. Furthermore, reverse transcription
      quantitative polymerase chain reaction and western blot analyses confirmed that
      knockdown of KIN17 decreased the expression of matrix metalloproteinase 7,
      epidermal growth factor receptor and v-myc avian myelocytomatosis viral oncogene
      homolog. The results of the present study indicate that Kin17 is markedly
      overexpressed in NSCLC tissues compared with benign lung lesion and peritumoral
      tissue. The upregulation of KIN17 may serve an important role in the metastasis
      of NSCLC cells. These results indicate that Kin17 is a novel diagnostic and
      prognostic biomarker of NSCLC, in addition to being a potential therapeutic
      target for the treatment of patients with NSCLC.

PMID- 28454392
TI  - KLF7 overexpression in human oral squamous cell carcinoma promotes migration and
      epithelial-mesenchymal transition.
AB  - Kruppel-like factor 7 (KLF7) is a member of the KLF family of zinc finger
      transcription factors, and was the first KLF cloned using complementary DNA and
      polymerase chain reaction (PCR) techniques with human vascular endothelial cells
      as a template. In addition, KLF7 is known as the ubiquitous Kruppel-like factor,
      as it is widely expressed in numerous human tissues at low levels. In the present
      study, the function of KLF7 in migration and epithelial-mesenchymal transition
      (EMT), which are associated with tumor progression, was investigated in human
      oral squamous cell carcinoma (OSCC) cells. Genes that were differentially
      expressed in normal vs. OSCC tissue were identified in the Gene Expression
      Omnibus database, which identified upregulation of KLF7 in OSCC. The expression
      and subcellular location of KLF7 was then analyzed using immunohistochemistry.
      KLF7 expression was measured in three OSCC cell lines, and the two cell lines
      with the highest (HN13) and lowest (CAL27) KLF7 expression were selected for
      further analysis. Subsequently, HN13 cells with reduced KLF7 expression (sh-HN13)
      and CAL27 cells overexpressing KLF7 (OE-CAL27) were constructed. Transwell
      migration and wound healing assays were then used to analyze the migration of the
      cells. In addition, mRNA and protein expression levels of the EMT markers E
      cadherin, N-cadherin, vimentin and snail were detected using reverse
      transcription-quantitative PCR and western blotting. KLF7 overexpression in OSCC
      was validated using tissue immunohistochemistry, which identified moderate to
      high cytoplasmic staining of KLF7 in OSCC cells. KLF7 knockdown and
      overexpression altered the migration ability of sh-HN13 and OE-CAL27 cells, which
      decreased and increased significantly respectively. Expression of E-cadherin, N
      cadherin, vimentin and snail was markedly altered in sh-HN13 and OE-CAL27 cells,
      indicating changes in EMT status. The results of the present study suggest that
      KLF7 overexpression changes the migratory behavior of OSCC cells, and induces EMT
      and lymph node metastasis through the expression of snail.

PMID- 28454393
TI  - Diagnosing and discriminating between primary and secondary aneurysmal bone
      cysts.
AB  - Aneurysmal bone cysts (ABCs) are benign bony lesions frequently accompanied by
      multiple cystic lesions and aggressive bone destruction. They are relatively rare
      lesions, representing only 1% of bone tumors. The pathogenesis of ABCs has yet to
      be elucidated. In the present study, a series of 22 cases of primary and
      secondary ABC from patients treated in Department of Orthopedic Surgery,
      Kagoshima University Hospital (Kagoshima, Japan) from 2001-2015 were
      retrospectively analyzed. The average age at the time of diagnosis of primary ABC
      was 17.9 years. Intralesional curettage and artificial bone grafting were
      performed in the majority of the patients with primary ABC. The local recurrence
      rate following curettage for primary ABC was 18%, and the cause of local
      recurrence was considered to be insufficient curettage. Although no adjuvant
      therapy was administered during the surgeries, it may assist the prevention of
      local recurrence in certain cases. The cases of secondary ABC were preceded by
      benign bone tumors, including fibrous dysplasia, giant cell tumors,
      chondroblastoma and non-ossifying fibroma. The features of the secondary ABC
      typically reflected those of the preceding bone tumor. In the majority of cases,
      distinguishing the primary ABC from the secondary ABC was possible based on
      characteristic features, including age of the patient at diagnosis and the tumor
      location. In cases that exhibit ambiguous features, including a soft tissue mass
      or a thick septal enhancement on the preoperative magnetic resonance images, a
      biopsy must be obtained in order to exclude other types of aggressive bone
      tumors, including giant cell tumor, osteosarcoma and telangiectatic osteosarcoma.

PMID- 28454394
TI  - Variation and significance of secretory immunoglobulin A, interleukin 6 and
      dendritic cells in oral cancer.
AB  - The present study aimed to determine changes in the concentration of secretory
      immunoglobulin A (SIgA) and interleukin 6 (IL-6) in the saliva of patients with
      oral cancer, to evaluate the abnormal expression of cluster of differentiation
      (CD) 1a, CD83, CD80 and CD86 on dendritic cells (DCs) of oral cancer tissues and
      to discuss the interaction between SIgA, IL-6 and DCs in oral cancer. A total of
      40 patients between 27 and 70 years of age, median age 52 years, with primary
      oral cancer were enrolled in the present study, and a group of 20 healthy male
      and female volunteers was used as the control group. The concentration of SIgA
      and IL-6 in the saliva of the preoperative patients was determined by ELISA. The
      expression levels of CD1a, CD83, CD80 and CD86 were detected by
      immunohistochemistry and flow cytometry, which was performed on histopathological
      sections from paraffin-embedded tumor and corresponding adjacent control tissues.
      The specimens were assessed using the semi-quantitative immunoreactive score
      (IRS). The concentration of SIgA in the saliva from patients with oral cancer
      decreased, whereas the IL-6 level significantly increased compared with the
      control subjects (P<0.05). In addition, the decrease of SIgA level and increase
      of IL-6 level exhibited a negative correlation (r=-0.543, P<0.05). According to
      the IRS score, the expression levels of CD1a, CD83, CD80 and CD86 in the cancer
      tissue were lower than the expression levels of the control group (P<0.05).
      Furthermore, the expression of CD80 and CD86 exhibited no correlation with
      histological grade or pathological type (P>0.05), but exhibited a negative
      correlation with clinical stage and lymph node metastasis (P<0.05). The
      concentration of SIgA and IL-6 in saliva may be used as an auxiliary diagnostic
      indicator for oral cancer. The detection of CD80 and CD86 expressed on DCs in
      oral cancer tissue may be useful for the diagnosis and evaluation of the
      prognosis of tumors. The present study hypothesized that the use of SIgA vaccines
      or IL-6 inhibitors may be useful for reversing the immune deficiency associated
      with DCs in oral cancer.

PMID- 28454395
TI  - Notch1 targeted regulation of mir-224/LRIG2 signaling for the proliferation and
      apoptosis of cervical cancer cells.
AB  - In the present study, we explored the participation of Notch1 targeted regulation
      of mir-224/LRIG2 gene signal pathway in proliferation and apoptosis of cervical
      cancer cells. Forty-nine cases of cervical cancer lesion samples from cervical
      cancer patients treated in our hospital from February 2013 to February 2015 were
      chosen as subjects (the observation group), and cervical samples of healthy women
      (42 cases) during the same period were used as the control group. We determined
      the mRNA and protein expression of Notch1, mir-224, and LRIG2 genes. We also
      analyzed the mutual relationship between Notch1 gene expression and cervical
      cancer. The Notch1 genes in the cervical cancer cells (HeLa) were silenced and
      overexpressed to measure cancer apoptosis with flow cytometry. After obstruction
      of the Notch1 signal pathway, the mRNA and protein expression in the mir-224 and
      LRIG2 genes was also measured. It was found that in comparison to the control
      group, Notch1 gene expression in the observation group was significantly higher
      (p<0.05), cell growth was suppressed in Notch1 silent cell strains but
      accelerated in overexpressed Notch1 cells. The silencing of Notch1 genes can lead
      to the reduction of mir-224/LRIG gene and protein levels, while overexpression of
      the Notch1 genes increased the mir-224/LRIG gene and protein levels. In
      conclusion, the Notch1 gene is positively related to cervical cancer and can
      promote the occurrence of the disease. The potential mechanism shows that Notch1
      gene can regulate cervical cancer cell proliferation by regulating the mir
      224/LRIG2 signal pathway.

PMID- 28454396
TI  - Treatment with the herbal formula Songyou Yin inhibits epithelial-mesenchymal
      transition in hepatocellular carcinoma through downregulation of TGF-beta1
      expression and inhibition of the SMAD2/3 signaling pathway.
AB  - It was previously reported that treatment with the herbal formula Songyou Yin
      (SYY) may serve a role in attenuating epithelial-mesenchymal transition (EMT). In
      the present study, the effect of treatment with SYY on transforming growth factor
      beta1 (TGF-beta1)-induced EMT was investigated and the potential underlying
      molecular mechanisms were evaluated. MHCC97H cells were pretreated with SYY for 4
      weeks and subsequently named MHCC97HSYY cells. Simultaneously, MHCC97H cells were
      cultured for 4 weeks without SYY and used as a negative control. Western blot
      analysis and enzyme-linked immunosorbent assays demonstrated that treatment with
      SYY inhibited EMT-associated changes and TGF-beta1 expression in MHCC97H cells.
      MHCC97H and MHCC97HSYY cells were treated with 10 ng/ml TGF-beta1 to induce EMT.
      The results of the present study demonstrated that pretreatment with SYY markedly
      inhibited TGF-beta1-induced morphological changes, and reversed the expression of
      the EMT markers E-cadherin and N-cadherin. In addition, expression levels of the
      TGF-beta1 downstream proteins, phosphorylated mothers against decapentaplegic
      homologs (p-SMAD)2 and 3, were reduced. Transwell assays indicated that
      pretreatment with SYY inhibited TGF-beta1-induced cancer cell invasion and
      migration. The results of the present study indicate that SYY inhibited EMT
      through attenuation of TGF-beta1 expression, and downregulation of p-SMAD2 and 3.

PMID- 28454397
TI  - Sphingosine kinase 1: A novel independent prognosis biomarker in hepatocellular
      carcinoma.
AB  - Sphingosine kinase 1 (Sphk1) is an oncogenic kinase that is responsible for the
      phosphorylation of sphingosine to sphingosine-1-phosphate (S1P). Mounting
      evidence suggests that Sphk1 serves a crucial role in the proliferation and
      development of a variety of human cancer cells. However, the role of Sphk1 in
      hepatocellular carcinoma (HCC) has not been fully elucidated. Therefore, the
      expression of Sphk1 was examined in 127 formalin-fixed, paraffin-embedded HCC
      tissues using immunohistochemistry, and its clinical implications and prognostic
      significance were analyzed. As a result, the expression of Sphk1 in HCC tissue
      was revealed to be significantly higher than in normal tissue (P<0.01). In
      addition, Sphk1 expression was significantly associated with tumor size, tumor
      stage and histological differentiation (all P<0.05). The patients with low Sphk1
      expression had higher overall survival and recurrence-free survival rates
      compared with patients with high Sphk1 expression. Furthermore, Sphk1-specific
      shRNA was used to downregulate the expression of Sphk1 in HCC cell lines,
      including hepatoblastoma G2 and HCC-9724. The CRISPR/Cas9 based transcription
      activation system was used to upregulate Sphk1 expression in the normal live
      cell, L02. Cell proliferation, mRNA expression and protein expression were
      measured using Cell Counting Kit-8, reverse transcription polymerase chain
      reaction and western blot analysis in the transfected cells. To the best of our
      knowledge, the present study provides the first evidence that Sphk1 promotes HCC
      cell proliferation and is involved in tumor progression. Notably, the data
      presented suggest that Sphk1 may be a potential independent prognosis biomarker
      for the treatment of HCC.

PMID- 28454398
TI  - Immunological effects of vaccines combined with granulocyte colony-stimulating
      factor on a murine WEHI-3 leukemia model.
AB  - Granulocyte colony-stimulating factor (G-CSF) mobilizes regulatory T cells
      (Tregs) from bone marrow into the peripheral blood, by reducing the expression of
      stromal cell-derived factor-1alpha (SDF-1alpha). However, G-CSF has rarely been
      studied in acute myeloid leukemia (AML) immunotherapy. The present study
      performed a Transwell migration assay in vitro to determine the contribution of
      SDF-1alpha to the migration of leukemia cells, and the effects of G-CSF were
      evaluated. The effects of G-CSF on SDF-1alpha and Tregs in the AML
      microenvironment were examined, by employing a WEHI-3-grafted BALB/c mouse AML
      model (AML-M4). It is evident that G-CSF reversed immunosuppression of the AML
      microenvironment by reducing SDF-1alpha in bone marrow and elevating Tregs in the
      peripheral blood in in vivo studies. Furthermore, AML mice treated with vaccines
      combined with G-CSF achieved a longer survival time than those treated with
      vaccines without G-CSF, showing the efficiency of the regimen. The present study
      demonstrates the effects of G-CSF on the mobilization of leukemia cells and Tregs
      into the peripheral blood. In addition, immunotherapy with G-CSF priming
      represents a promising therapeutic strategy of targeting the immunosuppression.

PMID- 28454399
TI  - Inhibition of lung cancer growth by HangAmDan-B is mediated by macrophage
      activation to M1 subtype.
AB  - Re-education of tumor-associated macrophages (TAMs) toward antitumor effectors
      may be a promising therapeutic strategy for the successful treatment of cancer.
      HangAmDan-B (HAD-B), a herbal formula, has been used for stimulating immune
      function and activation of vital energy to cancer patients in traditional Korean
      Medicine. Previous studies have reported the anti-angiogenic and anti-metastatic
      effects of HAD-B; however, evidence on the immunomodulatory action of HAD-B was
      not demonstrated. In the present study, immunocompetent mice were used to
      demonstrate the suppression of the in vivo growth of allograft Lewis lung
      carcinoma (LLC) cells, by HAD-B. In addition, HAD-B inhibited the in vitro growth
      of LLC cells by driving macrophages toward M1 polarization, but not through
      direct inhibition of tumor cell growth. Furthermore, culture media transfer of
      HAD-B-treated macrophages induced apoptosis of LLC cells. Results of the present
      study suggest that the antitumor effect of HAD-B may be explained by stimulating
      the antitumor function of macrophages. Considering the importance of re-educating
      TAMs in the regulation of the tumor microenvironment, the present study may
      confer another option for anti-cancer therapeutic strategy, using herbal
      medicines such as HAD-B.

PMID- 28454400
TI  - Stevioside induced cytotoxicity in colon cancer cells via reactive oxygen species
      and mitogen-activated protein kinase signaling pathways-mediated apoptosis.
AB  - The role of mitogen-activated protein kinase (MAPK) signaling pathways in cell
      growth and differentiation has been well established. The present study aimed to
      investigate the anti-proliferative effect of stevioside on human colon cancer HT
      29 cells. Additionally, the effect of stevioside on cell cycle arrest and MAPK
      signaling pathways in HT-29 cells was explored. Stevioside was observed to
      significantly inhibit cancer cell growth at a dose of 5 uM at 48 and 72 h. A dose
      dependent increase in the apoptosis rate was observed with cell cycle arrest at
      G2/M phase. In addition, caspase-9 and caspase-3 activity also increased. An
      increase in reactive oxygen species (ROS) production and a decrease in the
      mitochondrial membrane potential indicated that the mitochondrial-mediated
      intrinsic pathway is responsible for apoptotic activity. These results were
      additionally verified by the elevated expression level of phosphorylated p38 and
      extracellular signal-regulated kinase mitogen-activated protein kinases (MAPKs).
      Additionally, by inhibiting ROS production and MAPK activation, the
      antiproliferative effect of stevioside was suppressed, confirming the hypothesis
      that ROS and MAPK proteins induce apoptosis in human colon cancer HT-29 cells.

PMID- 28454401
TI  - Safety and effectiveness of localized lung resection combined with neoadjuvant
      chemotherapy in the treatment of stage I-II non-small cell lung cancer.
AB  - This study was conducted to evaluate the safety and effectiveness of localized
      lung resection combined with neoadjuvant chemotherapy in the treatment of stage I
      II non-small cell lung cancer (NSCLC). A total of 88 patients, who were admitted
      to our hospital for first diagnosis and treatment, were selected. The patients
      were divided into control group (n=40 cases) and observation group (n=48 cases)
      according to the last digit of the admission number. The control group was
      treated with minimally invasive localized lung resection by thoracoscope. The
      observation group underwent the same procedure combined with two cycles of
      systemic neoadjuvant chemotherapy before the surgery was adopted in the
      observation group. The effects of both treatments were compared. The operation
      time, intraoperative blood loss and postoperative drainage volume of observation
      group were significantly lower than those of the control group (P<0.05). The
      surgical resection rate and margin negative rate of observation group were higher
      than those of control group, while the occurrence rate of complications was lower
      than that of control group; results were statistically significant (P<0.05). The
      serum neutrophil gelatinase associated lipocalin (lipocalin-2/NGAL), matrix
      metalloproteinase-9 (MMP-9) and carcinoembryonic antigen (CEA) levels of two
      groups after the treatment were lower than those before; however, levels in the
      observation group exhibited a distinct decrease. The difference has statistical
      significance (P<0.05). The follow-up time of two groups was 3-38 months and the
      median time was 20.5 months. The tumor survival period of observation group was
      not prolonged, however, the survival rate and quality rate of life were enhanced;
      the difference has statistical significance (P<0.05). Localized lung resection
      combined with neoadjuvant chemotherapy can effectively improve the surgical
      effect of stage I-II NSCLC, prolong the survival period, enhance the survival
      rate, decrease the occurrence rate of complications and reduce the tumor related
      factors lipocalin-2, MMP-9 and CEA levels.

PMID- 28454402
TI  - miR-215 suppresses proliferation and migration of non-small cell lung cancer
      cells.
AB  - The expression of microRNA-215 (miR-215) in non-small cell lung cancer (NSCLC)
      tissues and the effects of miR-215 on the proliferation and migration of NSCLC
      cells were investigated. qRT-PCR was used to detect the expression of miR-215 in
      NSCLC tissues and paired normal tumor-adjacent lung tissues; MTT assay, transwell
      assay and soft-agar assay were used in vitro to evaluate the role of miR-215 on
      proliferation, migration and cell clonality on NSCLC cells, after transfecting
      miR-215 mimics to NSCLC cell line A549 or miR-215 to H1299. miR-215 was
      significantly decreased in NSCLC tissues compared to the paired normal tissues;
      Overexpression of miR-215 in A549 cells resulted in reduction of the cell
      proliferation, migration and cell clonality, while downregulation of miR-215 in
      H1299 cells could promote cell proliferation, migration and clonality. In
      conclusion, miR-215 was downregulated in NSCLC tissues and may play a key role in
      the development of NSCLC.

PMID- 28454403
TI  - miR-22 promotes apoptosis of osteosarcoma cells via inducing cell cycle arrest.
AB  - To study the effects of miR-22 on the proliferation and the apoptosis of
      osteosarcoma MG-63 cell line and to explore the potential molecular mechanism
      that miR-22 regulates this biological process. Quantitive real-time polymerase
      chain reaction (RT-qPCR) was performed to explore the miRNA level of miR-22. The
      MG-63 cell line was infected with miR-22 mimics for establishment of miR-22
      overexpression. Non-infected cells were in blank group and cells infected with
      empty vector were served as negative control (NC group). MTT assay was conducted
      to measure cell viability. The cell cycle and apoptosis were explored using flow
      cytometry and the apoptosis-related markers were detected by western blotting. RT
      qPCR results revealed that the miR-22 miRNA level in the MG-63 cells was
      significantly lower than that in osteoblasts (P<0.05). MTT assay showed that the
      MG-63 cells infected with miR-22 mimics exhibited markedly decreased
      proliferation ability compared with blank and empty vector (NC) groups. Next, we
      found that overexpression of miR-22 remarkably increased the apoptosis of the MG
      63 cells, evidenced from the flow cytometry results and elevated Bax and reduced
      Bcl-2. Furthermore, results revealed that percentage of the cells at G0/G1 phase
      in miR-22 mimic group (66.75+/-3.67%) was significantly higher than blank (52.9+/
      2.58%) and NC (50.5+/-2.45%) groups. miR-22 attenuated the proliferation and
      induced the apoptosis of the MG-63 cells via promoting G0/G1 cell cycle arrest.
      Thus, miR-22 may have the potential to be a novel therapeutic in treatment of
      osteosarcoma.

PMID- 28454404
TI  - Correlation between epidermal growth factor receptor mutations and the expression
      of estrogen receptor-beta in advanced non-small cell lung cancer.
AB  - Epidermal growth factor receptor (EGFR) mutations are more common in non-small
      cell lung cancer (NSCLC) and in female patients of East Asian origin. Therefore,
      the present study investigated the presence of EGFR mutations in advanced NSCLC,
      and assessed its correlation with clinicopathologic factors, including the
      expression of estrogen receptor-beta (ER-beta) and patient prognosis. The present
      study performed a retrospective analysis of 83 patients with stage IIIB-IV NSCLC.
      The expression of ER-beta and p53 were examined using immunohistochemical
      methods. EGFR mutations were evaluated using the amplification refractory
      mutation system. The expression of ER-beta and p53 were detected in 37 (45.6%)
      and 48 (57.8%) of the patient tumors, respectively. EGFR mutations were
      identified in 36 (45.4%) cases. EGFR mutations were more frequently observed in
      ER-beta-negative tumors (26/46; 56.5%), compared with ER-beta-positive tumors
      (10/37; 27%). The expression of ER-beta was significantly associated with EGFR
      mutations with an odds ratio (OR) of 0.241 (P=0.029). However, no significant
      correlation was observed between the expression of p53 and mutations in EGFR
      (OR=1.792; P=0.340). In addition, the expression of ER-beta and lymph node
      metastasis were associated with poor prognosis, whereas EGFR mutations were
      significantly associated with favorable prognosis in terms of progression-free
      survival rates. However, there was no prognostic significance associated with the
      expression of p53. In conclusion, the expression of ER-beta was significantly
      correlated with the presence of EGFR mutations. The expression of ER-beta and
      mutations of EGFR were found to be prognostic factors for survival rates in
      patients with advanced NSCLC.

PMID- 28454405
TI  - Expression of B-cell translocation gene 2 is associated with favorable prognosis
      in hepatocellular carcinoma patients and sensitizes irradiation-induced
      hepatocellular carcinoma cell apoptosis in vitro and in nude mice.
AB  - B-cell translocation gene 2 (BTG2) proteins have been reported to be putative
      tumor suppressors in various cancer types. The present study first assessed BTG2
      expression in 44 human liver cancer tissue specimens, then investigated BTG2
      expression in the regulation of hepatocellular carcinoma (HCC) cell apoptosis
      with or without radiotherapy in vitro and in vivo. The results revealed that BTG2
      protein expression was significantly reduced in HCC tissues, and associated with
      better survival for HCC patients (P=0.05). BTG2 overexpression also sensitized
      Huh7 cells to radiation-induced apoptosis in vitro and in a nude mouse model,
      although restoration of BTG2 expression per se did not affect the viability and
      apoptosis of HCC cells. Future studies would confirm the role of BTG2 in
      hepatoma, and further develop BTG2 as a therapeutic strategy for controlling HCC.

PMID- 28454406
TI  - Carcinoid syndrome from a carcinoid tumor of the pancreas without liver
      metastases: A case report and literature review.
AB  - A carcinoid tumor of the pancreas (CTP) is a rare pancreatic neoplasm, and
      usually presents with carcinoid syndrome (CS). CS consists of the classic symptom
      triad of cutaneous flushing, diarrhea and valvular disease, and occurs in the
      majority of patients with liver metastases. In the present study, the patient
      presented with symptoms of CS. A diagnosis of CTP with CS was suspected due to
      high levels of urine 5-hydroxyindolacetic acid, and this was confirmed by a fine
      needle aspiration biopsy. Computed tomography showed extended lymphadenopathy,
      but no liver metastases. The patient was managed conservatively with octreotide
      long acting repeatable. To the best of our knowledge, this is the second
      literature case of CS associated with CTP without liver metastases.

PMID- 28454407
TI  - Downregulation of NPM expression by Her-2 reduces resistance of gastric cancer to
      oxaliplatin.
AB  - Nucleophosmin (NPM) and human epidermal growth factor receptor-2 (Her-2) are
      abnormally expressed in various types of human malignant tumors, including
      gastric cancer, and have been closely associated with cancer chemoresistance.
      However, their interaction and roles in oxaliplatin resistance are not fully
      understood. Therefore, the present study aimed to elucidate the relationship
      between NPM and Her-2 in gastric cancer cell lines and clinical samples, and
      further investigated their role in the resistance of gastric cancer to
      oxaliplatin. Western blotting and reverse transcription-quantitative polymerase
      chain reaction confirmed that NPM and Her-2 expression were significantly
      upregulated in gastric cancer cells and clinical samples, and that their
      expression levels were strongly correlated. However, Her-2 expression was not
      affected by upregulation or downregulation of NPM expression in gastric cancer
      cells. Cell counting kit-8 assays demonstrated that the cell sensitivity to
      oxaliplatin decreased simultaneously with an increase in NPM expression.
      Furthermore, inhibition of Her-2 expression using trastuzumab significantly
      increased the sensitivity of the cells to oxaliplatin, which occurred
      simultaneously with the downregulation of NPM. These results indicated that
      inhibition of NPM, as a Her-2 downstream signal, may be a novel strategy to
      overcome oxaliplatin-resistant gastric cancer, and that trastuzumab and
      oxaliplatin may exhibit a synergistic antitumor effect in Her-2-positive gastric
      cancer cells.

PMID- 28454408
TI  - Astrocyte elevated gene-1 promotes the proliferation and invasion of breast
      cancer cells by activating the Wnt/beta-catenin signaling pathway.
AB  - Astrocyte elevated gene-1 (AEG1) was identified to be overexpressed in breast
      cancer, and to be associated with the development of breast cancer. In the
      present study, AEG1 was identified as highly expressed in the MCF-7, MDA-MB-231
      and SK-BR-3 breast cancer cell lines and was detected in the MCF-10A normal
      breast epithelial cell line. The present study established an AEG1-knockdown MCF
      7 cell line to investigate the expression status of certain cancer-associated
      proteins. Western blotting demonstrated that AEG1 may affect cancer cell
      proliferation and invasion via activating the Wnt/beta-catenin signaling pathway,
      a hypothesis that has been supported by cell function tests. The results of the
      present study demonstrated that when AEG1 was significantly overexpressed in
      breast cancer cells it promoted cell proliferation and invasion via activating
      the Wnt/beta-catenin signaling pathway. Therefore, AEG1 may serve as a novel
      therapeutic target in breast cancer.

PMID- 28454409
TI  - Expression of IMP3 as a marker for predicting poor outcome in
      gastroenteropancreatic neuroendocrine neoplasms.
AB  - The aim of the present study was to investigate the expression and clinical
      significance of oncofetal protein insulin-like growth factor (IGF) II mRNA
      binding protein 3 (IMP3) in the differentiation of gastroenteropancreatic
      neuroendocrine neoplasm (GEP-NEN). A total of 162 patients who were diagnosed
      with GEP-NEN, and who underwent surgical or endoscopic resection from January
      2006 to March 2013, were enrolled in the study, including 85 cases of grade (G)1
      neuroendocrine tumors, 40 cases of G2 neuroendocrine tumors, 28 cases of G3
      neuroendocrine carcinomas and 9 cases of mixed stage adenoneuroendocrine
      carcinomas. The clinical and pathological data were recorded for analysis. The
      expression of IMP3, cluster of differentiation (CD)44, IGF1 receptor (IGF1R) and
      matrix metalloproteinase (MMP)2 was determined by immunohistochemistry. SPSS 13.0
      software was used for data processing and analyses, and P<0.05 was used to
      determine significance. Oncofetal protein IMP3 exhibited a high expression rate
      (74.69%) in GEP-NEN. IMP3-positive cases demonstrated significantly decreased
      overall and disease-free survival times, as compared with IMP3-negative cases
      (P=0.012). Overexpression of IMP3 was correlated with tumor grade, clinical
      stage, tumor size and poor prognosis (all P<0.05). Therefore, patients with
      overexpressed IMP3 had a poorer prognosis (P<0.01); COX regression analysis
      revealed that the overexpression of IMP3, the tumor grade, tumor size and
      metastasis of GEP-NEN were each associated with the clinical outcomes. The
      results also indicated that the expression rates of CD44, IGF1R and MMP2 in GEP
      NEN were 19.75, 53.7 and 55.56%, respectively. While it was negatively associated
      with the expression of CD44 (r=-0.131; P=0.096), the expression of IMP3 was
      positively correlated with the expression of IGF1R and MMP2 (r=0.288, P<0.01;
      r=0.208, P=0.008). In addition, the expression levels of IGF1R and MMP2 were
      positively associated (r=0.687; P<0.01). In conclusion, high IMP3 expression
      levels were determined to be associated with a high disease stage in patients
      with GEP-NEN, thus it may serve as a predictor for metastasis and poor clinical
      outcomes in GEP-NEN.

PMID- 28454410
TI  - Zerumbone inhibits melanoma cell proliferation and migration by altering
      mitochondrial functions.
AB  - It has been reported that zerumbone (ZER) has marked effects on the regulation of
      cell proliferation and migration in multiple types of cancer, and has anti-cancer
      effects on various types of malignant cell. However, the effects and underlying
      molecular mechanisms of treatment with ZER on melanoma cells remain unclear. In
      the present study, the effect of treatment with ZER on the proliferation,
      migration and mitochondrial function of the human melanoma cell line CHL-1 was
      investigated. The results of the present study indicated that treatment with ZER
      significantly inhibited CHL-1 cell proliferation (P<0.001). Cell migration
      analysis further demonstrated that ZER inhibited the migration of CHL-1 cells
      (P<0.001). Treatment with ZER significantly increased cellular reactive oxygen
      species levels (P<0.001), reduced matrix membrane potential (P<0.001), decreased
      ATP (P<0.001) and mitochondrial DNA (P<0.001) levels, and decreased mitochondrial
      transcription factor A mRNA levels (P=0.002). The results of the present study
      suggested that the inhibition of proliferation and migration was mediated by
      altered mitochondrial function. In conclusion, the results of the present study
      suggested that ZER has chemotherapeutic effects on human melanoma cells by
      altering mitochondrial function.

PMID- 28454411
TI  - Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell
      lung cancer.
AB  - Lung cancer is the most frequent cause of mortality in cancer patients; non-small
      cell lung cancer (NSCLC) accounts for ~80% of lung cancer cases. MicroRNAs
      (miRNAs) have been revealed to perform an important role in cancer development
      and progression. Based on a custom miRNA microarray analysis of patients with
      NSCLC, miRNA-615-3p (miR-615-3p) downregulation was identified in NSCLC tissues
      compared with normal lung tissues, which suggested that miR-615-3p acted as a
      tumor suppressor in lung cancer. The overexpression of miR-615-3p was then
      validated using 40 pairs of NSCLC and adjacent normal tissue samples using a
      TaqMan reverse transcription-quantitative polymerase chain reaction assay. In
      order to investigate the tumor suppressor function of miR-615-3p, the ectopic
      expression of miR-615-3p in the NSCLC A549, H1299 and H1650 cell lines was
      established. The results revealed that overexpressed miR-615-3p markedly
      inhibited cell proliferation and colony formation in the 3 NSCLC cell lines
      compared with the cells overexpressing the negative control sequence (NC).
      Additional investigation revealed that miR-615-3p overexpression significantly
      induced apoptosis and cell cycle arrest at the G1 phase in the A549, H1299 and
      H1650 cell lines compared with the cells overexpressing NC. Finally, ectopic
      expression of miR-615-3p was found to repress the cell migration and invasion of
      the 3 lung cancer cell lines. The results of the present study demonstrate, for
      the first time, that miR-615-3p functions as a tumor suppressor in NSCLC, and may
      be a novel potential molecular therapeutic target for patients with NSCLC.

PMID- 28454412
TI  - Comparison of the seleno-transcriptome expression between human non-cancerous
      mammary epithelial cells and two human breast cancer cell lines.
AB  - Breast cancer is the second most common cause of mortality in women; therefore,
      the identification of novel putative markers is required to improve its diagnosis
      and prognosis. Selenium is known to protect mammary epithelial cells from
      oxidative DNA damage, and to inhibit the initiation phase of carcinogenesis by
      stimulating DNA repair and apoptosis regulation. Consequently, the present study
      has focused attention on the selenoprotein family and their involvement in breast
      cancer. The present study performed a global analysis of the seleno-transcriptome
      expression in human breast cancer MCF-7 and MDA-MB231 cell lines compared with
      healthy breast MCF-10A cells using reverse transcription-quantitative polymerase
      chain reaction. The present data revealed the presence of differently expressed
      genes in MCF-7 and MDA-MB231 cells compared with MCF-10A cells: Four
      downregulated [glutathione peroxidase (GPX)1, GPX4, GPX5 and GPX7] and three
      upregulated (deiodinase iodothyronine, type II, GPX2 and GPX3) genes.
      Additionally, interactomic investigation were performed by the present study to
      evaluate the association between the downregulated and upregulated genes, and to
      identify putative HUB nodes, which represent the centers of association between
      the genes that are capable of direct control over the gene networks. Network
      analysis revealed that all differentially regulated genes, with the exception of
      selenoprotein T, are implicated in the same network that presents three HUB nodes
      interconnected to the selenoprotein mRNAs, including TP53, estrogen receptor 1
      and catenin-beta1 (CTNNB1). Overall, these data demonstrated for the first time,
      a profile of seleno-mRNAs specific for human breast cells, indicating that these
      genes alter their expression on the basis of the ER-positivity or negativity of
      breast cancer cells.

PMID- 28454413
TI  - Na7CrCuW11O39.16H2O induces apoptosis in human ovarian cancer SKOV3 cells through
      the p38 signaling pathway.
AB  - Ovarian carcinoma is a common malignant disease worldwide with a poor therapeutic
      response. The present study investigated the effects of Na7CrCuW11O39.16H2O
      (CrCuW11) on ovarian cancer cell growth and investigated the mechanisms
      underlying its actions. The effects of CrCuW11 on cell viability and apoptosis
      were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide
      (MTT) assay, acridine orange/ethidium bromide staining and electron microscopy in
      human ovarian cancer SKOV3 cells. The expression of bcl-2-like protein 4 (Bax), B
      cell lymphoma 2 (Bcl-2), cytochrome c, phosphorylated (p)-p38 and p38 was
      determined by western blot analysis. Caspase-3 activity was measured by caspase-3
      activity kit. CrCuW11 concentrations of 1.87*10-3 mol. l-1 at 12 h reduced
      viability induced apoptosis in SKOV3 cells in a concentration-and time-dependent
      manner. Forced expression of CrCuW11 upregulated the expression of certain
      proteins (Bax, cytochrome c, and p-p38), and downregulated Bcl-2 protein
      expression. Furthermore, CrCuW11 also enhanced caspase-3 activity. The p38
      inhibitor SB203580 was able to inhibit the activity of CrCuW11. Caspase-3 and p38
      signaling pathways were associated with CrCuW11-regulated multiple targets
      involved in SKOV3 cell proliferation. Therefore, the results of the present study
      indicated that CrCuW11 may be used as a novel clinical drug for the treatment of
      ovarian cancer.

PMID- 28454414
TI  - Analysis of EGFR mutation status in tissue and plasma for predicting response to
      EGFR-TKIs in advanced non-small-cell lung cancer.
AB  - The detection of mutations in the epidermal growth factor receptor (EGFR) gene in
      tumor tissues has been established as the gold standard for predicting the
      efficacy of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in
      advanced non-small-cell lung cancer (NSCLC). The current study aimed to
      investigate whether the presence of co-existing EGFR mutations in tumor tissue
      and in cell-free tumor DNA (ctDNA) in the plasma predicts a more favorable
      outcome of EGFR-TKI treatment in advanced NSCLC. A total of 287 NSCLC patients
      who had undergone EGFR-TKI treatment were enrolled and stratified into four
      subgroups: Wild-type EGFR in plasma and tissue specimens (B-/T-); mutated EGFR in
      plasma and tissue specimens (B+/T+); mutated EGFR in only in plasma samples (B+/T
      ); or mutated EGFR in only tissue specimens (B-/T+). EGFR mutations were tested
      using denaturing high-performance liquid chromatography and confirmed by
      amplification-refractory mutation system analysis. Of the 287 patients, 101 had
      mutations in both tissue and plasma samples and 103 had mutation in either tissue
      (n=65) or plasma (n=38). The median progression-free survival (mPFS) times were
      9.2 and 2.0 months in the B+/T+ and B-/T- groups, respectively. The mPFS times
      were 7.9 months in the B-/T+ group and 11.9 months in the B+/T-group (P=0.001).
      Among the 187 patients with available pre-EGFR-TKI plasma samples, 70 received
      first-line EGFR-TKI treatment, and the mPFS in the B+/T+ group was longer than in
      the B-/T+ or B+/T- groups (18.8 vs. 9.4 vs. 6.9 months; P=0.003). In second-line
      setting of EGFR-TKI therapy, the groups of patients with EGFR mutation in ctDNA,
      regardless of the mutation status in the tissues, exhibited longer mPFS times
      compared with the B-/T+ group (10.0 vs. 5.8 months; P=0.044). The results suggest
      that co-existence of EGFR mutations in tissue and ctDNA predict longer PFS times
      for NSCLC patients who receive first-line EGFR-TKI therapy. In addition, real
      time detection in ctDNA is an excellent predictor for the efficacy of second- or
      higher line EGFR-TKI therapy.

PMID- 28454415
TI  - STAT3 activation and risk of recurrence in meningiomas.
AB  - Several studies have suggested that activation of signal transducer and activator
      of transcription 3 (STAT3) is associated with initiation, progression and
      metastasis of numerous types of malignancy. However, the role of the Janus kinase
      interleukin 6-STAT3 signaling pathway in the pathogenesis and recurrence of
      meningiomas is unknown. The present study evaluated STAT3 activation by western
      blotting and immunohistochemistry and assessed its association with Ki-67
      labeling in 13 cases of meningioma in which frozen tissue and >=5.5-year follow
      up information were available, and in formalin-fixed meningioma tissues from 14
      cases with an 8.4-year follow-up. The results of the western blot analysis
      indicated that STAT3 phosphorylation was markedly higher in grade II meningiomas
      compared with that in grade I, with mean densitometric values of 8.6 and 1.7
      following normalization to actin, respectively. High STAT3
      phosphorylation/activation was identified in 2 of 3 recurrent World Health
      Organization (WHO) grade I meningiomas and 0 of 3 non-recurrent meningiomas.
      Strong STAT3 phosphorylation/activation signal was also found in 2 of 4 recurrent
      grade II meningiomas and 1 of 3 non-recurrent cases. According to the
      immunohistochemistry results, phospho-STAT3 was not increased in WHO grade II
      tumors compared with that in grade I tumors, and was not significantly different
      between recurrent and non-recurrent cases. Ki-67 labeling was significantly
      increased in grade II vs. grade I tumors, and was also significantly increased in
      recurrent compared with non-recurrent grade I meningiomas. The results of the
      current study suggest that, while detection of phosphorylated/activated STAT3 may
      be useful in isolated cases, identifying activation may be of little value in
      predicting recurrence.

PMID- 28454416
TI  - Survivin DEx3 as a biomarker of thyroid cancers: A study at the mRNA and protein
      level.
AB  - Survivin and its splice variants DEx3 and 2B are involved in pathogenesis of
      numerous types of cancer. Proliferating cell nuclear antigen (PCNA) level
      correlates with cellular proliferation. The present study aimed to analyze the
      potential utility of survivin and its splice variants DEx3 and 2B as biomarkers
      for thyroid cancer. PCNA, survivin and its splice variants DEx3 and 2B
      expressions were analyzed in 22 tissue samples (15 thyroid cancers and 7 benign
      lesions) by reverse transcription-quantitative polymerase chain reaction and
      immunohistochemistry (IHC). There was significantly higher staining for survivin
      (P=0.019), survivin DEx3 (P=0.001), survivin 2B (P=0.0149) and PCNA (P=0.0237) in
      thyroid malignant tumors when compared with benign lesions. The receiver
      operating characteristics curve analysis has shown that the cut-off points of
      survivin IHC expression >2 [sensitivity 46.7%; specificity 100%; area under curve
      (AUC) 0.810; P=0.0005] and survivin DEx3 IHC expression >0 (sensitivity 86.7%;
      specificity 100%; AUC 0.933; P<0.0001) were the best predictors of thyroid
      malignancy. Additionally, PCNA staining >1 (sensitivity 93.3%; specificity 71.4%;
      AUC 0.790; P=0.0243) and survivin 2B >2 (sensitivity 46.7%; specificity 100%; AUC
      0.824; P=0.0002) were the best predictors of thyroid cancer. In conclusion, the
      present study exhibited that survivin DEx3 expression has high specificity and
      sensitivity for discrimination between benign thyroid lesions and cancers.
      Survivin DEx3 may be considered a biological marker of thyroid malignancy and
      therefore applied in clinical practice.

PMID- 28454417
TI  - miR-185 enhances the inhibition of proliferation and migration induced by
      ionizing radiation in melanoma.
AB  - Melanoma is an aggressive malignancy that is increasingly common and exhibits a
      poor patient survival rate. Radiotherapy is the primary option for patients with
      melanoma, particularly those who are not candidates for surgery; however, the
      therapeutic effect is limited due to the relative radioresistance of melanoma to
      ionizing radiation (IR). It has been reported that microRNAs (miRNAs) serve a
      vital role in determining the radiosensitivity of tumors; however, little is
      known concerning the radiosensitization of melanoma using miRNA. In the present
      study, the radiosensitization effect of miRNA 185 (miR-185), which has been
      demonstrated to reduce renal cancer radioresistance, was investigated in B16
      cells, a skin melanoma cell line derived from C57/BL mice, was investigated. Cell
      proliferation and scratch wound healing assays were used to determine the
      proliferative and migratory abilities of B16 cells. Annexin V/propidium iodide
      double staining was used to determine the apoptosis induced by IR. A tumor
      formation assay was performed to determine the radiosensitization effect of miR
      185 on melanoma cells in vivo. Proliferation marker protein Ki-67, and
      hematoxylin and eosin staining were used to assess the proliferative activity and
      histological changes, respectively. The results of the present study demonstrated
      that miR-185 suppresses cellular proliferation and migration, and enhances IR
      induced apoptosis, and the inhibition of proliferation and migration, in vitro
      and in vivo, which provides an insight into understanding the radiosensitization
      of melanoma using miRNA.

PMID- 28454418
TI  - Epigenetic silencing of protocadherin 10 in colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common types of malignant tumor in the
      world and occurs through a multi-step process resulting from the accumulation of
      genetic and epigenetic alterations of the genome. Although the molecular
      mechanisms of the pathogenesis of CRC remain unclear, the inactivation of tumor
      suppressor genes (TSGs) through promoter methylation serves an important role.
      Aberrant methylation is a well-defined marker of CRC. At present, the epigenetic
      silencing of protocadherin 10 (PCDH10) has been identified as an important TSG
      with key roles in colorectal carcinogenesis, invasion and metastasis as a
      frequent and early event. Advances in gene methylation detection in tumor tissues
      and body fluids have led to the development of non-invasive screening methods for
      CRC. The present study aimed to review the epigenetic alteration of PCDH10 in CRC
      development, and the potential of PCDH10 to be a non-invasive biomarker for CRC.

PMID- 28454419
TI  - Neutrophil-lymphocyte ratio predicts survival in pancreatic neuroendocrine
      tumors.
AB  - Although the prognostic role of neutrophil-lymphocyte ratio (NLR) has been
      confirmed in a variety of tumors, the prognostic role of NLR in pancreatic
      neuroendocrine tumors (PNETs) has not been examined. The present study was
      performed to assess the role of NLR as a prognostic factor in patients with
      PNETs. Clinical data were retrospectively retrieved from a single institution.
      The best cut-off value for baseline NLR levels was determined by the receiver
      operating characteristic (ROC) curve and area under the ROC curve. The primary
      event was overall survival and event times were assessed by the Kaplan-Meier
      method. Potential factors associated with the elevation of NLR in PNETs were
      examined. A total of 165 consecutive patients with pathologically confirmed PNETs
      were included in this study. The cutoff value of NLR was 2.4 by ROC curve (area
      under ROC curve, 0.70). NLR >2.4 was found to be a poor prognostic factor in the
      univariate and multivariate analyses. Patients with a NLR value >2.4 had a higher
      proportion of tumor size at >3 cm (P=0.001), TNM stage III or IV (P=0.019), and
      G2/G3 (P=0.003). We concluded that NLR is an independent predictor of overall
      survival for patients with PNETs. Aberrant elevation of NLR identifies high-risk
      patients with aggressive characteristics.

PMID- 28454420
TI  - Study of the expression and function of ACY1 in patients with colorectal cancer.
AB  - Aminoacylase 1 (ACY1) is important for regulating the proliferation of numerous
      types of cancer. However, the expression and mechanisms underlying the function
      of ACY1 in colorectal cancer remain unclear. In order to investigate the
      expression and function of ACY1 in colorectal cancer, tumor tissue and blood
      samples were collected for analysis from 132 patients diagnosed with colorectal
      cancer. Reverse transcription-quantitative polymerase chain reaction analysis and
      western blotting identified significantly increased expression of ACY1 mRNA in
      colorectal tumor tissue (P<0.05 vs. adjacent normal tissue) and notably increased
      ACY1 protein levels. This ACY1 mRNA expression was found to be positively
      correlated with tumor stage. In addition, plasma ACY1 concentration was increased
      in patients with colorectal cancer compared with healthy controls. Furthermore,
      in vitro knockdown of ACY1 in human colorectal cancer HT-29 cells was shown to
      inhibit proliferation and increase apoptosis. This effect was found to be
      associated with the activation of ERK1 and TGF-beta1 signaling. In conclusion,
      the results of the present study suggest that ACY1 promotes tumor progression,
      and thus may be a potential target for the diagnosis and treatment of colorectal
      cancer.

PMID- 28454421
TI  - Notch is a critical regulator in cervical cancer by regulating Numb splicing.
AB  - Cervical cancer, which is the second most common female malignancy, is
      characterized by the consistent presence of human papillomavirus. Inappropriate
      activation of Notch signaling has been associated with various types of cancer;
      however, the role of Notch in cervical cancer remains unclear. The present study
      aimed to investigate the role of Notch in cervical cancer. The methods used
      included the generation of plasmids, viability assays, polymerase chain reaction
      and western blotting The present findings demonstrated that cervical cancer
      samples also consistently exhibit abnormal activation of the Notch pathway. The
      data also indicated that different Numb isoforms may have opposite effects on the
      proliferation of cervical cancer cells. As a result, the activated Notch
      signaling pathway regulates the alternative splicing of the Numb gene, which
      affects the proliferation of the cervical cancer cells. These findings suggest
      that activated Notch signaling may lead to the development of cervical cancer by
      regulating Numb splicing. Thus, Numb splice variants may be a potential clinical
      marker for indicating cervical cancer genesis and development.

PMID- 28454422
TI  - The role of MRP1 in the multidrug resistance of colorectal cancer.
AB  - The role of multidrug resistance associated protein 1 (MRP1) in the multidrug
      resistance (MDR) of colorectal cancer (CRC) remains unclear. The present study
      aimed to investigate the effect of MRP1 in MDR CRC and its therapeutic potential
      for the treatment of patients with this disease. The human MDR CRC cell lines HCT
      8 and Colo205 were established through stable exposure to 5-florouracil (5-FU)
      over a 5-month period. MRP1 was knocked-down in MDR CRC cells through the
      transfection of short hairpin RNA targeting MRP1 (shMRP1). Western blotting was
      performed to assess the efficiency of this silencing. MTT and apoptosis assays
      were conducted to detect cell viability and apoptosis, respectively. Compared
      with their parental cells, HCT-8/5-FU and Colo205/5-FU cells were 23.1 and 15.8
      times more resistant to 5-FU, and 17.2 and 20.9 times more resistant oxaliplatin,
      respectively. The knockdown of MRP1 resulted in the attenuation of the MDR
      phenotype through the induction of apoptosis. The shMRP1-transfected Colo205/5-FU
      cells were injected subcutaneously into the right scapular region of BALB/c nude
      mice and tumor size was measured for 15 days post-injection. This in vivo
      experiment demonstrated that MRP1 knockdown inhibited tumor growth. On the 9, 12
      and 15th day post-injection, tumor volume in the shMRP1-transfected Colo205/5-FU
      cell-injected group was significantly lower compared with that in the Colo205/5
      FU cell-injected group (day 9, 2.1+/-0.8 vs. 6.9+/-1.9 mm3, P=0.009; day 12,
      3.1+/-1.4 vs. 14.3+/-4.0 mm3, P=0.008; day 15, 4.8+/-2.7 vs. 21.3+/-3.4 mm3; all
      P<0.001). These results demonstrate that MRP1 serves a role in the MDR phenotype
      of CRC through inhibiting apoptosis and may serve as a potential therapeutic
      target for inhibition, which would increase the efficacy of other
      chemotherapeutic agents in the treatment of CRC.

PMID- 28454423
TI  - The nutritional herb Epimedium grandiflorum inhibits the growth in a model for
      the Luminal A molecular subtype of breast cancer.
AB  - The Luminal A subtype of breast cancer expresses the estrogen receptor (ER)-alpha
      and progesterone receptor (PR), but not the human epidermal growth factor
      receptor (HER)-2 oncogene. This subtype of breast cancer responds to endocrine
      therapy involving the use of selective estrogen receptor modulators and/or
      inhibitors of estrogen biosynthesis. However, these therapeutic agents are
      frequently associated with long-term systemic toxicity and acquired tumor
      resistance, emphasizing the need to identify non-toxic alternative treatments for
      chemo-endocrine therapy responsive breast cancer. The present study utilized the
      human mammary carcinoma-derived, ER+/PR+/HER-2- MCF-7 cell line as a model of the
      Luminal A subtype of breast cancer to examine the growth inhibitory effect of the
      Chinese nutritional herb Epimedium grandiflorum (EG) and determine the mechanisms
      underlying this effect. MCF-7 cells maintained in a serum-depleted culture medium
      retained their ability to grow in response to 17beta-estradiol (E2). Treatment of
      the MCF-7 cells with EG resulted in dose-dependent inhibition of E2-promoted
      growth. Mechanistically, EG inhibited E2-promoted cell cycle progression through
      G1 stage arrest and modulated the cellular metabolism of E2, increasing the
      formation of the anti-proliferative metabolites 2-hydroxyestrone and estriol.
      Long-term treatment of MCF-7 cells with EG inhibited E2-promoted anchorage
      independent growth, a surrogate in vitro biomarker of tumorigenesis. In
      conclusion, the results of the present study demonstrate the growth inhibitory
      effects of EG on MCF-7 cells and identified clinically relevant mechanistic leads
      for its anti-tumorigenic efficacy.

PMID- 28454424
TI  - Association between polymorphisms in TP53 and MDM2 genes and susceptibility to
      prostate cancer.
AB  - Tumor protein 53 (TP53), a tumor suppressor gene, is a vital cellular cancer
      suppressor in multicellular organisms. Murine double minute-2 (MDM2) is an
      oncoprotein that inhibits TP53 activity. A number of studies have examined the
      association of TP53 and MDM2 polymorphisms with the risk of common forms of
      cancer, but the findings remain inconclusive. The present study aimed to evaluate
      the impact of the 40-bp insertion/deletion (I/D) polymorphism (rs3730485) in the
      MDM2 promoter region and the 16-bp I/D polymorphism (rs17878362) in TP53 on the
      susceptibility of prostate cancer (PCa) in a sample of the Iranian population.
      This case-control study included 103 patients with pathologically confirmed PCa
      and 142 patients with benign prostatic hyperplasia. The MDM2 40-bp I/D and TP53
      16-bp I/D polymorphism was determined using polymerase chain reaction analysis.
      The results demonstrated that the MDM2 40-bp I/D polymorphism increased the risk
      of PCa in a co-dominant inheritance model [odds ratio (OR)=1.88; 95% confidence
      interval (CI)=1.11-3.19; P=0.023, D/D vs. I/I], while this variant marginally
      increased the risk of PCa in a dominant model (OR=1.69; 95% CI=1.00-2.83;
      P=0.051, I/D+D/D vs. I/I). No significant association was observed between the
      TP53 16-bp I/D polymorphism and PCa. In conclusion, the present study
      demonstrated that the 40-bp I/D polymorphism in the MDM2 promoter increased the
      risk of PCa in an Iranian population. Further investigations with diverse
      ethnicities and larger sample sizes are required to verify these results.

PMID- 28454425
TI  - Whole-body low-dose computed tomography in multiple myeloma staging: Superior
      diagnostic performance in the detection of bone lesions, vertebral compression
      fractures, rib fractures and extraskeletal findings compared to radiography with
      similar radiation exposure.
AB  - The primary objective of the present prospective study was to compare the
      diagnostic performance of conventional radiography (CR) and whole-body low-dose
      computed tomography (WBLDCT) with a comparable radiation dose reconstructed using
      hybrid iterative reconstruction technique, in terms of the detection of bone
      lesions, skeletal fractures, vertebral compressions and extraskeletal findings.
      The secondary objective was to evaluate lesion attenuation in relation to its
      size. A total of 74 patients underwent same-day skeletal survey by CR and WBLDCT.
      In CR and WBLDCT, two readers assessed the number of osteolytic lesions at each
      region and stage according to the International Myeloma Working Group (IMWG)
      criteria. A single reader additionally assessed extraskeletal findings and their
      significance, the number of vertebral compressions and bone fractures. The
      radiation exposure was 2.7+/-0.9 mSv for WBLDCT and 2.5+/-0.9 mSv for CR
      (P=0.054). CR detected bone involvement in 127 out of 486 regions (26%;
      P<0.0001), confirmed by WBLDCT. CR underestimated the disease stage in 16% and
      overestimated it in 8% of the patients (P=0.0077). WBLDCT detected more rib
      fractures compared with CR (188 vs. 47; P<0.0001), vertebral compressions (93 vs.
      67; P=0.010) and extraskeletal findings (194 vs. 52; P<0.0001). There was no
      correlation observed between lesion size (>=5 mm) and its attenuation (r=-0.006;
      P=0.93). The inter-observer agreement for the presence of osteolytic lesions was
      kappa=0.76 for WBLDCT, and kappa=0.55 for CR. The present study concluded that
      WBLDCT with hybrid iterative reconstruction technique demonstrates superiority to
      CR with an identical radiation dose in the detection of bone lesions, skeletal
      fractures, vertebral compressions and extraskeletal findings, which results in up
      or downstaging in 24% patients according to the IMWG criteria. The attenuation
      of osteolytic lesions can be measured with the avoidance of the partial volume
      effect.

PMID- 28454426
TI  - Prevalence of human papillomavirus infection of the anal canal in women: A
      prospective analysis of high-risk populations.
AB  - Infection with certain types of human papillomavirus (HPV) has been associated
      with the development of cervical and anal cancer. Worldwide, the incidence of
      anal cancer has increased markedly. The present study aimed to evaluate the
      prevalence of HPV infection of the uterine cervix and anal canal in human
      immunodeficiency virus (HIV)- and non-HIV-infected risk populations. Cervical and
      anal HPV swabs and cytology samples were collected from 287 patients at the
      University Hospital of Munich, Germany between 2011 and 2013. Patients were
      divided into HIV-negative controls (G1) and two risk groups, including HIV
      negative patients with cytological abnormalities of the cervix (G2) and HIV
      infected patients (G3). Data, including clinical parameters, were analysed. The
      risk groups had significantly more positive results for HPV in the anus (71.03
      and 83.15% for G2 and G3, respectively), as compared with G1. The predominant HPV
      genotypes found in the anus were high-risk HPV genotypes, which were
      significantly correlated with concomittant cervical HPV findings. In the risk
      groups, a significant association between the cytological findings and HPV
      detection in the cervix was found, while the results of the anus revealed no
      significance. The results of the present study suggested that the prevalence of
      HPV infection in the anal canal of risk populations is high. Furthermore,
      patients with abnormal cervical cytology results and HIV-infected women,
      irrespective of their individual cervical findings, may have a risk of
      concomittant anal high-risk HPV infection. Based on the predominant HPV genotypes
      found in the study, HPV vaccination could reduce the incidence of anal cancer.
      Nevertheless, high-risk patients should be intensively screened for anal squamous
      intraepithelial abnormalities to avoid invasive cancer stages.

PMID- 28454427
TI  - Chemoresistance in pancreatic cancer: Emerging concepts.
AB  - Pancreatic cancer is one of the most lethal types of cancer in the world. The
      incidence of pancreatic cancer increases each year with no significant decrease
      in mortality. Pancreatic cancer is a complex disease, and this complexity is
      partly attributed to late diagnosis, an aggressive phenotype, environmental
      factors and lack of effective treatment options. Surgical resection followed by
      adjuvant chemotherapy is the treatment of choice for early stage cancer, whereas
      gemcitabine is the standard first line therapy for patients with advanced stage
      disease. Treatment regimens comprising folinic acid, 5-fluorouracil, irinotecan,
      oxaliplatin and nab-paclitaxel have demonstrated modest effects in improving
      median survival rates. A number of other chemotherapeutics are currently
      undergoing clinical trials as components of combination therapies with
      gemcitabine. An increasing number of novel molecular targets and cellular
      pathways are being identified, which highlights the complexity of this disease.
      The development of chemoresistance to gemcitabine is multifactorial and there
      exists an interplay between pancreatic cancer cells, the tumor microenvironment
      and cancer stem cells. These components appear to be governed by a complex
      network of non-coding RNAs such as micro RNAs and long non-coding RNAs. In the
      present study, studies describing previous research on the understanding of the
      factors associated with the development of chemoresistance to gemcitabine in
      pancreatic cancer are reviewed. A comprehensive understanding of the multiple
      pathways of chemoresistance is key to develop next generation therapeutics to
      pancreatic cancer.

PMID- 28454428
TI  - The regulation of proteins associated with the cytoskeleton by hepatitis B virus
      X protein during hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is a major malignant disease worldwide, and
      chronic hepatitis B virus (HBV) infection is one of the primary causes for this
      type of cancer. Hepatitis B virus X protein (HBx) is a non-structural protein
      encoded by the viral genome that has significant effects on the pathogenesis of
      HCC. With the development of high-throughput assays and technologies, the
      abnormal HBx-induced expression of certain cellular proteins with assorted
      biological functions has been investigated. These target proteins identified by
      various methods include specific proteins associated with the cellular
      cytoskeleton, which contribute to HBx-induced hepatocarcinogenesis. In addition,
      the cytoskeletal proteins deregulated by HBx are involved in cell morphogenesis,
      adhesion, migration and proliferation. This review aims to summarize the current
      understanding of the expression profiles of HBx-associated cytoskeletal proteins,
      as well as their complex functions and underlying mechanisms in
      hepatocarcinogenesis. Considering that the potential therapeutics for various
      types of tumors may function through the stabilization of cytoskeletal proteins
      in order to restrict cellular movement and limit intracellular processes,
      clarifying the mechanisms underlying protein-associated cytoskeleton
      dysregulation by HBx may provide novel possibilities and potent therapeutic
      targets for HBV-associated HCC.

PMID- 28454429
TI  - Polyphenolic compounds from Korean Lonicera japonica Thunb. induces apoptosis via
      AKT and caspase cascade activation in A549 cells.
AB  - Lonicera japonica Thunb. (L. japonica T.) has historically been used in Korean
      herbal medicine due to its anticancer and protective effects on the respiratory
      system. In the present study, the polyphenolic compounds in L. japonica T. were
      investigated using high-performance liquid chromatography coupled with tandem
      mass spectrometry, and its anticancer effects on A549 non-small-cell lung cancer
      cells were studied. Polyphenolic compounds potentially inhibit A549 cells in a
      dose-dependent manner. Flow cytometry and western blot analysis demonstrated that
      polyphenolic compounds induce apoptosis by regulating the protein expression
      levels of caspases, poly-(ADP-ribose) polymerase and the B-cell lymphoma-2
      associated X-protein/B-cell lymphoma-extra large ratio. Furthermore, polyphenolic
      compounds inhibited mitochondrial membrane potential activity. Caspase-3 activity
      was increased in a dose-dependent manner and polyphenolic compounds inhibited the
      activation of protein kinase B by dephosphorylation. These results suggest that
      polyphenolic compounds in A549 cells indicate the anticancer activity through the
      induction of apoptosis.

PMID- 28454430
TI  - WT1-associated protein is a novel prognostic factor in pancreatic ductal
      adenocarcinoma.
AB  - Although Wilms tumor 1 (WT1)-associated protein (WTAP) was initially found to be
      a specific WT1-binding protein, it has increasingly attracted attention because
      of its oncogenic role in various types of malignancies, including
      cholangiocarcinoma, glioblastoma and acute myeloid leukemia. However, the
      clinical impact of WTAP on pancreatic ductal adenocarcinoma (PDAC) is still
      unknown. A total of 145 patients who underwent surgical treatment from 2004 to
      2008 were enrolled in the present study. The cytoplasmic and nuclear expression
      of WTAP in tumor and adjacent normal tissues was examined by immunohistochemical
      analysis in order to investigate the relationship between WTAP and the
      clinicopathological factors and prognosis of patients with PDAC. The nuclear and
      cytoplasmic expression of WTAP in tumor tissues was significantly higher compared
      with non-tumor tissues (P<0.001). High expression of WTAP in the nucleus was
      significantly associated with gender (P=0.010) and tumor stage (P=0.020), while
      high expression of WTAP in the cytoplasm was significantly associated with gender
      (P=0.018), histological grade (P=0.047) and perineural invasion (P=0.028). In
      addition, a univariate analysis revealed that high nuclear expression of WTAP in
      tumor tissues was significantly associated with poor overall survival (P<0.001),
      as well as several clinicopathological variables, including gender and N stage.
      In a multivariate Cox regression analysis, nuclear WTAP expression was identified
      as an independent prognostic indicator for PDAC (relative risk, 1.855; 95%
      confidence interval, 1.033-3.333; P=0.039). The results of the present study
      indicated that high nuclear expression of WTAP is a valuable molecular biomarker
      of a poor prognosis among patients with PDAC.

PMID- 28454431
TI  - Cytokeratin 17 and Ki-67: Immunohistochemical markers for the differential
      diagnosis of keratoacanthoma and squamous cell carcinoma.
AB  - The clinical and histopathological distinction between keratoacanthoma (KA) and
      squamous cell carcinoma (SCC) is essential, but frequently difficult to make. The
      utility of CK17 and Ki-67 expression in distinguishing between KA and SCC was
      investigated. Immunohistochemical staining patterns for CK17 and Ki-67 were
      evaluated in 24 KA and 27 SCC cases. The pattern of staining was evaluated as
      central, peripheral or diffuse, according to the basal/peripheral and
      suprabasal/central cell staining of tumor lobules. The sensitivity and
      specificity of the central CK17 staining pattern in the identification of KA were
      92 and 70%, respectively. Additionally, the sensitivity and specificity of the
      diffuse Ki-67 staining pattern in the identification of SCC were 81 and 100%,
      respectively. The results of the present study suggest that a diffuse Ki-67
      staining pattern may be used to diagnose SCC, while a central CK17 staining
      pattern indicates KA. However, the KA-like SCC cases exhibited mixed patterns,
      which limits the effectiveness of these markers.

PMID- 28454432
TI  - Prognostic and predictive role of COX-2, XRCC1 and RASSF1 expression in patients
      with esophageal squamous cell carcinoma receiving radiotherapy.
AB  - Identification of biomarkers for predicting radiosensitivity would be useful for
      administering individualized radiotherapy (RT) to patients with esophageal
      cancer. The aim of the present study was to evaluate the association between
      cyclooxygenase-2 (COX-2), X-ray repair cross complementing group 1 (XRCC1), ras
      association domain family 1 (RASSF1) protein expression, clinicopathological
      characteristics, radiosensitivity and survival rate in 76 patients with
      esophageal squamous cell carcinoma (ESCC) who were treated with RT. Positive
      expression of COX-2, XRCC1 and RASSF1 was identified by immunohistochemistry in
      81.6, 52.6 and 59.2% of ESCC cases, respectively. Negative COX-2 expression was
      associated with tumor (T) stage, node (N) stage, clinical stage and complete
      response (P<0.05), but not with gender, age, tumor location, differentiation
      degree, lesion length, progression-free survival (PFS) or overall survival (OS;
      P>0.05). XRCC1 expression was not associated with the clinicopathological
      features of ESCC, response to RT, PFS or OS. Positive RASSF1 expression was
      associated with the clinical stage, response to RT, PFS and OS (P<0.05), but not
      with gender, age, tumor location, T stage, N stage, differentiation degree or the
      lesion length (P>0.05). In the subgroup analysis, RASSF1 positive/XRCC1 negative
      expression was correlated with a longer median OS and PFS (P<0.05). Multivariate
      analyses revealed that the tumor response and RASSF1 expression were significant
      prognostic factors. Therefore, positive RASSF1 expression is associated with ESCC
      RT sensitivity, and may be a useful independent prognostic factor for ESCC.

PMID- 28454433
TI  - Deregulation of miR-193b affects the growth of colon cancer cells via
      transforming growth factor-beta and regulation of the SMAD3 pathway.
AB  - MicroRNA-193b (miRNA-193b) is often differentially expressed and is an important
      regulator of gene expression in colon cancer. The aim of the present study was to
      determine whether miRNA-193b affects cell growth in colon cancer and to
      investigate the potential underlying mechanisms. Patients with colorectal cancer
      (CRC; n=20) and healthy volunteers (n=10) were enrolled from the Department of
      Gastrointestinal Surgery Center, First Affiliated Hospital of Sun Yat-Sen
      University (Guangzhou, China). Western blot analysis was used to evaluate the
      protein expression of SMAD3 and transforming growth factor-beta (TGF-beta) in the
      patient samples. It was determined that miRNA-193b expression was markedly
      elevated in the CRC tissue samples. Furthermore, silencing of miRNA-193bin SW620
      CRC cells by specific inhibitors significantly reduced the cell proliferation and
      induced apoptosis. In addition, the downregulation of miRNA-193b significantly
      activated the protein expression of SMAD3 and TGF-beta, and promoted caspase-3
      activity in SW620 cells. The results of the present study suggested that the
      deregulation of miRNA-193b may affect cell growth in colon cancer via the TGF
      beta and SMAD3 signaling pathways.

PMID- 28454434
TI  - F10, a novel hydatidiform mole-associated gene, inhibits the paclitaxel
      sensitivity of A549 lung cancer cells by downregulating BAX and caspase-3.
AB  - F10 is a novel hydatidiform mole (HM)-associated gene that was initially
      identified during a study into the pathogenesis of HMs. However, the role of the
      F10 gene requires further investigation. Our, previous studies have indicated
      that F10 may be involved in the malignant transformation of HMs and the
      development of certain types of adenocarcinoma, and that the overexpression of
      F10 may lead to excessive proliferation and decreased apoptosis of A549 cells.
      The present study aimed to investigate whether F10 may suppress the sensitivity
      of A549 lung cancer cells to paclitaxel therapy. A previously established F10
      overexpressing A549 cell line (A549-F10) was treated with paclitaxel, using
      untransfected A549 cells and A549-mock cells (non-carrier A549) as the controls.
      These three groups of cells were subsequently examined by an MTT cell
      proliferation assay and a TUNEL-fluorescein isothiocyanate/Hoechst 33258
      apoptosis assay. A western blot analysis was used to determine the expression
      levels of the pro-apoptotic genes B-cell lymphoma-2-associated X protein (BAX)
      and caspase-3. The effects of paclitaxel treatment on the proliferation and
      apoptosis of A549 cells were compared between the aforementioned cell lines. It
      was revealed that F10 inhibited the chemosensitivity of A549 cells to paclitaxel,
      as demonstrated by the decreased rates of growth inhibition and apoptosis in the
      A549-F10 group compared with the two control groups. Furthermore, the A549-F10
      cells treated with paclitaxel exhibited significantly lower expression levels of
      the pro-apoptotic genes. The results of the current study demonstrate that F10
      may inhibit the chemosensitivity of A549 cells to paclitaxel and that this
      inhibitory effect may be mediated by the downregulation of BAX and caspase-3
      expression, which subsequently inhibits cell apoptosis.

PMID- 28454435
TI  - 15-Deoxy-Delta12,14-prostaglandin J2 inhibits migration of human thyroid
      carcinoma cells by disrupting focal adhesion complex and adherens junction.
AB  - Metastasis is frequently observed in human follicular thyroid carcinoma. The
      present study investigated the peroxisome proliferator-activated receptor gamma
      agonist, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), and its effect on the
      migration of CGTH W-2 human thyroid carcinoma cells. 15d-PGJ2 decreased the
      survival rate of CGTH W-2 cells in a dose-dependent manner. The Transwell
      migration assay demonstrated that 15d-PGJ2 reduced the migration rate of CGTH W-2
      cells by 35% following treatment with 30 uM 15d-PGJ2 compared with control cells.
      The cell adhesion assay indicated that, following 15d-PGJ2 treatment for 24 h,
      cell adhesion decreased by 26% compared with the control group. The expression
      levels of focal adhesion proteins, including integrin beta1, phospho-focal
      adhesion kinase and p-paxillin, were downregulated following treatment with 15d
      PGJ2. Immunostaining revealed that the puncta of vinculin were reduced and the
      actin stress fiber was disassembled following 15d-PGJ2 treatment. By contrast,
      p120-catenin (p120-ctn) and beta-catenin levels staining accumulated in the
      region of the lamellipodium following 15d-PGJ2 treatment. Membrane fractionation
      revealed that p120-ctn and N-cadherin were decreased in the cell membrane, but
      increased in the cytoplasm of 15d-PGJ2-treated cells. Therefore, 15d-PGJ2
      inhibited human thyroid carcinoma cell migration and this may be due to the
      impairment of focal adhesion complexes and the accumulation of p120-ctn in the
      cytoplasm in the region of the lamellipodium.

PMID- 28454436
TI  - SATB1 promotes epithelial-mesenchymal transition and metastasis in prostate
      cancer.
AB  - Special AT-rich sequence-binding protein-1 (SATB1) is associated with cancer
      progression and poor clinical outcome. The present study aims to evaluate whether
      SATB1 affects the biological behaviors of prostate cancer (PCa), and furthermore,
      to elucidate whether this effect works through the epithelial-mesenchymal
      transition (EMT) pathway. Firstly, the expression of SATB1 was investigated in a
      series of PCa tissues as well as in a panel of PCa cell lines. Cell
      proliferation, migration and invasion were evaluated in SATB1 knockdown and
      overexpressed PCa cell lines by MTT and Transwell assays. The results showed that
      the expression of SATB1 was markedly upregulated in PCa tissues and all PCa cell
      lines (P<0.001). Ectopic expression of SATB1 promoted PCa cell proliferation and
      migration. Knockdown of SATB1 repressed the ability of cell proliferation and
      migration of PCa cells. In addition, inhibition of SATB1 could reverse the EMT
      processes through upregulation of E-cadherin and downregulation of vimentin. The
      present study provided evidence that SATB1 may act as a potential therapeutic
      target in PCa patients.

PMID- 28454437
TI  - Polycomb group expression signatures in the malignant progression of gliomas.
AB  - Polycomb group (PcG) proteins form at least two key complexes, namely polycomb
      repressive complex 1 and polycomb repressive complex 2. These complexes are
      involved in the progression of various cancers. Systematic research has not been
      conducted on the aberrant expression of PcG members in gliomas. Using the Chinese
      Glioma Genome Atlas data set, PcG expression patterns between normal brain
      tissues and glioma samples were analyzed, and a PcG-based classifier was then
      developed using BRB Cox regression and risk-score model. These results were
      validated in an independent GSE16011 set. A total of six PcGs [chromobox protein
      homolog (CBX) 6, CBX7, PHD finger protein 1, enhancer of zeste homolog 2 (EZH2),
      DNA (cytosine-5-)-methyltransferase 3beta (DNMT3B) and polyhomeotic-like protein
      2] were identified to be associated with glioma grade. Survival analysis then
      revealed a five-PcG gene signature one protective gene (enhancer of zeste homolog
      1) and four risky genes (EZH2, PHD finger protein 19, DNMT3A and DNMT3B), which
      may identify patients with high risk of poor prognosis of glioma. Multivariate
      Cox analysis indicated that the five-PcG signature was an independent prognostic
      biomarker. These findings indicated that a novel prognostic classifier, five-PcG
      signature, served as an independent prognostic marker for patients with glioma.

PMID- 28454438
TI  - CHK2 is involved in the p53-independent radiosensitizing effects of valproic
      acid.
AB  - Radiotherapy is an effective treatment for the majority of types of localized
      solid cancer. However, the risk of side effects to the surrounding normal tissues
      limits radiotherapeutic approaches. Whilst the mechanism of action of valproic
      acid, an inhibitor of histone deacetylase, remains unknown, the inhibitor is a
      potential antineoplastic radiosensitizer. The present study demonstrated the in
      vitro radiosensitizing effects of valproic acid on the human breast cancer MCF7
      cell line, and revealed that valproic acid increased the level of DNA breakage,
      apoptosis and senescence. In addition, western blot analyses revealed that
      valproic acid induced tumor suppressor protein (p)53 and p21 expression, and
      activated checkpoint kinase 2 (CHK2) in MCF7 cells and primary mouse embryonic
      fibroblasts. Notably, treatment with valproic acid also induced increases in the
      level of p21 protein levels and CHK2 activity in p53-null colon cancer HCT116
      cells. Furthermore, the present study demonstrated that valproic acid-induced
      radiosensitization was largely dependent on the activity of CHK2. The results of
      the present study reveal that valproic acid may exhibit clinical utility with
      respect to increasing the anticancer efficacy of radiotherapy by affecting the
      level of p53.

PMID- 28454439
TI  - Oct4 induces EMT through LEF1/beta-catenin dependent WNT signaling pathway in
      hepatocellular carcinoma.
AB  - Octamer 4 (Oct4), a member of the Pit-Oct-Unc transcription factor family
      required to maintain self-renewal and pluripotency of embryonic stem cells, has
      been previously identified to be associated with tumorigenesis and malignant
      transformation of numerous types of cancer including hepatocellular carcinoma
      (HCC). The present data shows that Oct4 enhances cancer stem cell properties and
      increases invasion ability in the Huh7 cell line. To increase understanding of
      the role of Oct4 in HCC, the present study used a functional genomics approach
      and analyzed the resulting transcriptional profiles to identify Oct4-dependent
      genes in Huh7. Affymetrix GeneChip Human genome U133 Plus 2.0 Arrays were used to
      determine differential gene expression profiles and then validated by
      quantitative polymerase chain reaction. The present study found that altered
      expression of 673 genes (fold-change >=2) affected multiple signaling pathways
      linked with self-renew and metastasis. Among these differentially expressed
      genes, the present study noticed that the key component of the WNT signaling
      pathway lymphoid enhancer binding factor 1 (LEF1) and Twist Family BHLH
      transcription factor 1 were upregulated by Oct4, whilst cadherin 2 was
      downregulated. Additional studies found that the nuclear beta-catenin aggregation
      was increased in Oct4 overexpressed HCC cell lines. These results suggest that
      Oct4 regulates LEF1 to active LEF1/beta-catenin dependent WNT signaling pathway
      and promote epithelial-mesenchymal transition. The present findings provide novel
      mechanistic insight into an important role of Oct4 in HCC.

PMID- 28454440
TI  - FFJ-3 inhibits PKM2 protein expression via the PI3K/Akt signaling pathway and
      activates the mitochondrial apoptosis signaling pathway in human cancer cells.
AB  - Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor
      biomarker and potential therapeutic target for the treatment of cancer. In the
      present study, FFJ-3, a structurally modified version of mollugin, an extract of
      the Traditional Chinese herbal medicine Rubia tinctorum (madder) was used in
      order to determine the anticancer activity of the compound and investigate the
      potential mechanisms underlying this effect in human cancer cells. The results of
      the present study revealed that FFJ-3 inhibited the survival of HepG2 human
      hepatoma cells, MCF-7 human breast cancer cells and A549 human lung
      adenocarcinoma cells using the MTT assay. In addition, FFJ-3 arrested cell cycle
      progression at G2/M and G1 in HepG2 and A549 cells, respectively. Further
      analyses demonstrated that FFJ-3 attenuated the expression of PKM2 protein via
      the inhibition of the phosphoinositide 3-kinase (PI3K)/Akt serine/threonine
      kinase (Akt) signaling pathway. Furthermore, treatment of all three cell types
      with FFJ-3 significantly increased apoptosis and decreased the mitochondrial
      membrane potential compared with the untreated control group. In addition, FFJ-3
      treatment increased the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X and
      activated the caspase-3 cascade. In conclusion, the inhibition of the PI3K/Akt
      signaling pathway and activation of the caspase-3 cascade by FFJ-3 were primarily
      responsible for the inhibition of cell proliferation and induction of apoptosis
      in MCF-7, HepG2 and A549 cells. The results of the present study suggest a
      potential therapeutic role for FFJ-3 in the treatment of human cancer.

PMID- 28454441
TI  - MicroRNA-130b promotes cell migration and invasion by inhibiting peroxisome
      proliferator-activated receptor-gamma in human glioma.
AB  - Glioma is the most common and aggressive type of primary brain tumor. MicroRNA
      (miR)-130b functions as a tumor-associated miR. The dysregulation of miR-130b is
      involved in numerous biological characteristics and properties of certain types
      of cancer. The present study revealed the function and possible molecular
      mechanism of miR-130b in glioma cells, reporting that the level of miR-130b was
      markedly higher, increasing progressively as the histologic grade of the glioma
      increased, compared with the level in normal tissues. Additionally, the present
      study demonstrated that patients with high miR-130b expression exhibited a poor 3
      year survival rate and miR-130b was an independent factor for predicting the
      prognosis of patients with glioma. The downregulation of miR-130b reduced
      invasion and migration in U373 and U87 cells. Furthermore, the downregulation of
      miR-130b increased peroxisome proliferator-activated receptor-gamma (PPARgamma)
      expression and inhibited epithelial-mesenchymal transition (EMT) in glioma cells.
      The present study identified PPARgamma as a direct target of miR-130b in glioma
      in vitro. Furthermore, PPARgamma knockdown was revealed to reduce the effect on
      EMT caused by the downregulation of miR-130b in U87 cells. The present study
      demonstrated that miR-130b promotes glioma proliferation, migration and invasion
      by suppressing PPARgamma and subsequently inducing EMT.

PMID- 28454442
TI  - Identification of target genes of cediranib in alveolar soft part sarcoma using a
      gene microarray.
AB  - The aim of the present study was to identify the target genes of cediranib and
      the associated signaling pathways in alveolar soft part sarcoma (ASPS). A
      microarray dataset (GSE32569) was obtained from the Gene Expression Omnibus
      database. The R software package was used for data normalization and screening of
      differentially expressed genes (DEGs). The Database for Annotation, Visualization
      and Integrated Discovery was used to perform Gene Ontology analysis. Gene Set
      Enrichment Analysis was performed to obtain the up- and downregulated pathways in
      ASPS. The Distant Regulatory Elements of co-regulated genes database was used to
      identify the transcription factors (TFs) that were enriched in the signaling
      pathways. A protein-protein interaction (PPI) network was constructed using the
      Search Tool for the Retrieval of Interacting Genes/Proteins database and was
      visualized using Cytoscape software. A total of 71 DEGs, including 59 upregulated
      genes and 12 downregulated genes, were identified. Gene sets associated with ASPS
      were enriched primarily in four signaling pathways: The phenylalanine metabolism
      pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, the taste
      transduction pathway and the intestinal immune network for the production of
      immunoglobulin A. Furthermore, 107 TFs were identified to be enriched in the MAPK
      signaling pathway. Certain genes, including those coding for Fms-like tyrosine
      kinase 1, kinase insert domain receptor, E-selectin and platelet-derived growth
      factor receptor D, that were associated with other genes in the PPI network, were
      identified. The present study identified certain potential target genes and the
      associated signaling pathways of cediranib action in ASPS, which may be helpful
      in understanding the efficacy of cediranib and the development of new targets for
      cediranib.

PMID- 28454443
TI  - miR-185-3p regulates the invasion and metastasis of nasopharyngeal carcinoma by
      targeting WNT2B in vitro.
AB  - MicroRNAs (miRs) have been recognised as important regulators of malignant
      behaviour in different types of human cancer, including nasopharyngeal carcinoma
      (NPC). A previous study by our group revealed that miR-185-3p regulates the
      radioresistance of NPC cells. The present study aimed to investigate the effect
      of miR-185-3p on NPC invasion and metastasis. Human NPC CNE-2 and 5-8F cell lines
      were transfected with a miR-185-3p mimic and miR-185-3p inhibitor, respectively,
      and their effects on the invasion and metastasis of these cells was assessed
      using a wound healing assay and Matrigel invasion assay. The target gene of miR
      185-3p, Wnt family member 2B (WNT2B) was silenced in 5-8F cells using siRNA in
      order to investigate its function in NPC. Data from the present study
      demonstrated that the expression of miR-185-3p was the highest in 5-8F and lowest
      in CNE-2 cells out of a range of NPC cell lines. Following the transfection of
      miR-185-3p mimic into CNE-2 cells, the wound healing and Matrigel invasion assays
      indicated that the migration and invasion ability of CNE-2 cells was
      significantly reduced compared with the negative control group. In addition, the
      inhibition of miR-185-3p in 5-8F cells significantly increased the capacity for
      migration and invasion. Furthermore, silencing WNT2B expression resulted in a
      significant reduction in the invasion and metastasis in 5-8F cells. The
      inhibition of miR-185-3p, which promotes invasion and metastasis, could be
      reversed through the silencing of WNT2B in 5-8F cells. The results of the present
      study indicate that miR-185-3p mediates the invasion and metastasis of NPC by
      targeting WNT2B in vitro.

PMID- 28454444
TI  - Anterior mediastinum invasion by multiple myeloma: A case report.
AB  - Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells in the
      bone marrow (BM) that secretes monoclonal paraproteins in the blood serum and
      urine. Bone marrow MM cells can invade and damage the functions of other tissues
      and organs, such as the lungs, spleen, liver, pancreas, kidneys and lymph nodes.
      However, the invasion of MM cells primarily located in the BM to the anterior
      mediastinum at the site of the thymus is an extremely rare event. The current
      study reports the case of a 53-year-old female who presented with MM with
      involvement of the anterior mediastinum. The diagnosis was based on clinical
      imaging analyses and the results from BM and laboratory examinations, local
      biopsy pathology and immunohistochemistry. The patient was administered two
      courses of chemotherapy (epirubicin, dexamethasone and thalidomide). As a result,
      the tumor reduced in size, but the laboratory examination indicated no
      significant change. Next, the patient was switched to one course of PAD
      chemotherapy (bortezomib, epirubicin and dexamethasone). The original tumor was
      significantly reduced in size following this chemotherapy, and all the indicators
      improved. The present study suggests that invasion of the thymus by MM may lead
      to immune disturbance arising from the abnormal thymus gland. In the clinic,
      extramedullary plasmacytoma in the thymus should be carefully distinguished from
      thymoma.

PMID- 28454445
TI  - Role of reactive oxygen species in the anticancer activity of botanicals:
      Comparing sensitivity profiles.
AB  - Numerous botanicals have been shown to exhibit in vitro and in vivo anticancer
      activity, some of which is the result of the induction of reactive oxygen species
      (ROS) in cancer cells with a high ROS content. The present study compared
      sensitivities to a series of botanicals among cancer cell lines, using an XTT
      viability test, in order to create a specific cancer-herb profile. Of the 27
      botanicals screened, 10 exhibited a cytotoxic effect, 7 of which were ROS
      mediated. The sensitivity profiles of the ROS-inducing botanicals in 10 cancer
      cell lines were similar, unlike 3 cytotoxic ROS-independent botanicals that
      displayed divergent botanical-specific profiles. The correlation between
      sensitivity profiles of ROS-inducing botanicals suggests a common mechanism of
      action, in contrast to the varied mechanism of ROS-independent botanicals. This
      implies that the investigation of the anticancer activity of botanicals should
      start with the examination of ROS-mediated activity. Further investigation of ROS
      sensitivity among various tumor types is required in order to guide research into
      developing evidence-based guidelines in the use of botanicals for cancer
      treatment.

PMID- 28454446
TI  - Lentivirus-mediated RNA interference of tripartite motif 68 inhibits the
      proliferation of colorectal cancer cell lines SW1116 and HCT116 in vitro.
AB  - Colorectal cancer is one of the most common types of cancer worldwide. Previous
      studies have revealed that certain members of tripartite motif (TRIM) proteins
      are involved in carcin ogenesis regulation, but little is known about the
      function of TRIM68 in human colorectal cancer. To investigate the role of TRIM68
      in colorectal cancer SW1116 and HCT116 cell lines, the present study conducted
      lentivirus-mediated knockdown against TRIM68 and demonstrated that depletion of
      TRIM68 notably inhibits colorectal cancer cell proliferation and colony formation
      ability. Cell cycle arrest in the G0/G1 phase and cycle accumulation in sub-G1
      phase provided evidence that TRIM68 may participate in the regulation of
      colorectal cancer tumorigenesis. The results revealed the significant role of
      TRIM68 in regulating colorectal cancer cell mitosis and indicated that TRIM68 may
      be a promising therapeutic target.

PMID- 28454447
TI  - Inhibitory effect and mechanism of exogenous mammalian sterile 20-like kinase 1
      on the growth of human colorectal cancer.
AB  - The present study aimed to observe the inhibitory effect and preliminary
      mechanism of exogenous mammalian sterile 20-like kinase 1 (MST1) on the growth of
      colorectal cancer SW480 cells. The SW480 cells were randomly divided into the
      following groups: Control, empty enhanced green fluorescent protein (EGFP)
      plasmid (pEGFP-N1), MST1 EGFP plasmid (pEGFP-MST1), 20 umol/l fluorouracil (5-FU)
      and pEGFP-MST1 + 5-FU. An MTS colorimetric assay was used to detect cell
      viability, Hoechst 33342 staining was used to observe cell apoptosis, and western
      blotting and immunohistochemistry were used to detect the levels of the proteins
      MST1, yes-associated protein (YAP), phospho-YAP1 (Ser127), p53 and p53
      upregulated modulator of apoptosis (PUMA). In addition, nude mice were injected
      with SW480 cells to assess the tumor inhibition rates. Compared with the control
      group, the growth inhibition and apoptosis rates, the levels of MST1, p53 and
      PUMA, and the ratios of phospho-YAP1/YAP in the pEGFP-MST1 and pEGFP-MST1 + 5-FU
      groups were increased significantly (P<0.01). Additionally, relative to the
      control group, the tumor inhibition rates in the nude mice transplanted with
      SW480 cells of the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were 48.52+/-1.63 and
      87.28+/-2.58%, respectively, and the positive rates of phospho-YAP1 (Ser127)
      protein in nuclei increased significantly (P<0.01). Overall, exogenous MST1
      effectively inhibited the proliferation and growth of transplanted human
      colorectal cancer cells and promoted cancer cell apoptosis. The mechanism
      involved may be associated with the increase of intracellular phospho-YAP1
      (Ser127) protein.

PMID- 28454448
TI  - GNAQ mutation R183Q as a potential cause of familial Sturge-Weber syndrome: A
      case report.
AB  - Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder whose etiology
      remains unclear. To investigate the genetic contribution underlying this disease,
      the genetic variants of a 4-generation family with a history of SWS was analyzed
      in the present study. SWS was diagnosed in 3 of the family members (II-1, III-11
      and IV-6). Sanger sequencing was performed to identify mutations in G protein
      subunit alphaq (GNAQ) and RAS p21 protein activator 1 exons in the 3 patients
      with SWS and other unaffected family members. Notably, a non-synonymous single
      nucleotide variant at codon 183 on exon 4 of the GNAQ gene was identified as the
      only pathogenic site. This variant generated a substitution of arginine (R) with
      glutamine and resulted in a change of function of the encoded protein.
      Evolutionary conservation analysis revealed that the mutated residue 183 (R) of
      GNAQ is highly conserved across several vertebrate species. Furthermore, an
      immunofluorescence staining assay demonstrated that the substitution of arginine
      with glutamine resulted in a change in the sub-cellular localization of the GNAQ
      recombinant protein in vitro. These findings may aid in the development of novel
      diagnostic markers and/or therapeutic targets for the treatment of patients with
      familial SWS.

PMID- 28454449
TI  - Bioinformatics analysis of the prognostic value of Tripartite Motif 28 in breast
      cancer.
AB  - Tripartite motif containing 28 (TRIM28) is a transcriptional regulator acting as
      an essential corepressor for Kruppel-associated box zinc finger domain-containing
      proteins in multiple tissue and cell types. An increasing number of studies have
      investigated the function of TRIM28; however, its prognostic value in breast
      cancer (BC) remains unclear. In the present study, the expression of TRIM28 was
      identified to be significantly higher in cancerous compared with healthy tissue
      samples. Furthermore, it was demonstrated that TRIM28 expression was
      significantly correlated with several clinicopathological characteristics of
      patients with BC, such as p53 mutation, tumor recurrence and Elston grade of the
      tumor. In addition, a protein-protein interaction network was created to
      illustrate the interactions of TRIM28 with other proteins. The prognostic value
      of TRIM28 in patients with BC was investigated using the Kaplan-Meier Plotter
      database, which revealed that high expression of TRIM28 is a predictor of poor
      prognosis in patients with BC. In conclusion, the results of the present study
      indicate that TRIM28 provides a survival advantage to patients with BC and is a
      novel prognostic biomarker, in addition to being a therapeutic target for the
      treatment of BC.

PMID- 28454450
TI  - De novo myoepithelial carcinoma with multiple metastases arising from a
      submandibular salivary gland: A case report.
AB  - Salivary gland carcinomas are rare tumors, representing ~0.5% of all
      malignancies. Myoepithelioma is also uncommon, representing ~1% of all salivary
      gland tumors. Myoepithelial carcinoma (MC) is even rarer, representing 0.2 to
      0.6% of all salivary gland tumors. We herein report a case of MC with multiple
      metastases arising from a submandibular gland in a 71-year-old male patient and
      present the associated imaging findings. The patient was considered to have a de
      novo type of myoepithelial carcinoma, which is reportedly associated with higher
      malignancy than the transformation type of the disease (i.e., a malignant change
      from pleomorphic adenoma or myoepithelioma). This was reflected in the multiple
      lung and bone metastases sites and strong positivity for p53 and Ki-67.

PMID- 28454451
TI  - Expression of GLP-1 receptor and CD26 in human thyroid C-cells: The association
      of thyroid C-cell tumorigenesis with incretin-based medicine.
AB  - Recent reports have demonstrated that long-term and high dosage treatments with
      incretin-based medicine, such as hormone glucagon-like peptide-1 (GLP-1) may
      induce thyroid C-cell pathological changes in rodents, rather than in humans.
      Doubts regarding the tumorigenic potential of GLP-1 analogues in human thyroid C
      cells remain. The present study aimed to determine the expression levels of GLP-1
      receptor (GLP-1R) and cluster of differentiation 26 (CD26) in the C-cells of
      thyroid tissues from non-neoplastic, medullary carcinoma and hyperplasia
      subjects, and to explore the potential clinical significance. The following cases
      were analyzed: Medullary thyroid carcinoma (n=62, including 59 paraffin-embedded
      samples and 3 fresh frozen samples), C-cell hyperplasia (n=20, paraffin-embedded
      samples) and non-neoplastic thyroid tissue samples (n=7, paraffin-embedded
      samples). GLP-1R and CD26 expression was detected using immunohistochemical
      staining and western blotting. There were significant differences in the
      expression levels of the two markers between medullary thyroid carcinoma and C
      cell hyperplasia, in addition to between medullary thyroid carcinoma and non
      neoplastic thyroid tissue following immunohistochemical staining. Similar
      significant differences in the expression of GLP-1R and CD26 were detected using
      western blot analysis in the medullary thyroid carcinoma compared with non
      neoplastic thyroid tissue sectioned from the aforementioned fresh frozen samples.
      There was a significant negative correlation between GLP-1R and CD26 expression.
      In addition, the present data indicated that GLP-1R expression was associated
      with the age of the patients with medullary thyroid carcinoma. These results
      suggested that GLP-1R and CD26 may be closely associated with the development of
      thyroid C-cell hyperplasia and medullary thyroid carcinoma, and indicated the
      importance of being aware of the side effects of incretin medicine.

PMID- 28454452
TI  - Flow cytometry-based immunophenotypic analysis of primary systemic light chain
      amyloidosis.
AB  - Using flow cytometry, the present study aimed to investigate the immunophenotypic
      characteristics of malignant plasma cells (PCs) in the bone marrow of patients
      with primary systemic light chain amyloidosis (AL) compared with the
      characteristics of patients with multiple myeloma (MM). Flow cytometric results
      of 51 patients with AL and 150 patients with MM were reviewed. The proportion of
      total bone marrow PCs in the patients with AL was significantly lower than that
      in the patients with MM, 1.35% (0.3-9.5%) vs. 9.7% (0.4-75.7%); (P<0.001). The
      cells in 24/51 patients with AL comprised two distinct populations: Normal PCs
      and malignant PCs, whereas only 11/150 patients with MM exhibited two
      populations. Patients with AL exhibited an increased cluster of differentiation
      (CD)19 expression compared with patients with MM, 4.5% (0.1-80.9%) vs. 1.6% (0.1
      33.6%; P<0.001) and reduced CD138, with 90.8% (30.4-99.9%) vs. 95.0% (40.7-100%;
      P=0.006) and CD56, with 61.0% (1.5-99.2%) vs. 98.3% (0.1-100%; P<0.001)
      expression in malignant PCs. Light chain restriction was identified in all
      patients with AL, and the proportion of lambda light chain restriction was 72.5%.
      The immunophenotypic characteristics of patients with AL demonstrated by flow
      cytometry were different compared with the characteristics of patients with MM in
      the number and composition of plasma cells, and the intracellular and
      extracellular expression of antigens. These differences may be associated with a
      less malignant phenotype of clonal PCs in AL than MM.

PMID- 28454453
TI  - Targeting assay of a fusion protein applied in enzyme prodrug therapy.
AB  - Tumor growth and metastasis are dependent on angiogenesis. The overexpression of
      integrin alphavbeta3 on angiogenic vessels and on numerous malignant human tumor
      cells suggests that these labeled ligands of integrin are potentially suitable
      for molecular imaging and in targeted therapy of tumors. In previous studies, we
      added a beta-lactamase variant with reduced immunogenicity to the cyclic peptide
      RGD4C, resulting in the fusion protein RGD4CbetaL, which is suitable for use in
      targeted enzyme prodrug therapy (TEPT), a promising treatment for tumors. The
      targeting of the aforementioned fusion protein serves an important role in TEPT.
      In the present study, RGD4CbetaL was labeled with 125I and the targeting effect
      on integrin-positive tumors was evaluated. The results demonstrated that the 125I
      RGD4CbetaL protein exhibited high levels of accumulation at the tumor site and
      rapid renal clearance, which revealed the potency and efficiency of RGD4CbetaL in
      TEPT.

PMID- 28454454
TI  - Chemotherapy regimen based on sorafenib combined with 5-FU on HIF-1alpha and VEGF
      expression and survival in advanced gastric cancer patients.
AB  - The present study investigated the effect of combined sorafenib chemotherapy on
      hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth
      factor (VEGF) expression and survival time of patients with advanced gastric
      cancer. From January 2010 to December 2011, 92 patients diagnosed with advanced
      gastric cancer were selected and randomly divided into the treatment group and
      control group. The treatment group was treated with sorafenib chemotherapy
      combined with 5-fluorouracil (5-FU), and the control group received 5-FU. The
      treatment course was 3-4 cycles. During the same period, 46 healthy persons
      admitted to the Second People's Hospital of Huaian were selected as the controls.
      A volume of 3-4 ml peripheral blood from each patient and control was collected
      before and after treatment. The expression levels of HIF-1alpha and VEGF in
      peripheral blood were measured by ELISA. The survival time of patients with
      advanced gastric cancer was followed and analyzed. Compared with healthy
      controls, serum levels of HIF-1alpha and VEGF were significantly higher in
      patients with advanced gastric cancer (P<0.05). After chemotherapy combined with
      sorafenib, the peripheral blood levels of HIF-1alpha and VEGF decreased
      significantly in the treatment group (P<0.05). The 5-year survival rate of
      patients in the two groups was followed. Compared with the control group, the 1
      year survival rate of the treatment group was significantly higher (P<0.05). In
      conclusion, chemotherapy combined with sorafenib can effectively reduce serum
      levels of HIF-1alpha and VEGF in patients with advanced gastric cancer, and
      improve their 1-year survival rate and prognosis. Therefore, it has significant
      clinical application value.

PMID- 28454455
TI  - Brainstem tuberculous abscesses successfully treated by microsurgical excision: A
      case report and review of the literature.
AB  - In patients without systemic manifestations of tuberculosis, isolated brainstem
      tuberculous abscesses are infrequently observed. The present study reports a rare
      case of two cystic tuberculous abscesses involving the dorsal aspect of the
      medulla oblongata in an otherwise healthy 14-year-old Chinese girl, whose primary
      complaint was respiratory distress. These lesions were successfully treated using
      a microsurgical excision approach and anti-tuberculosis therapy. Although rare,
      tuberculous abscesses should be considered in the differential diagnosis of
      isolated cystic brainstem lesions. The results of the present study indicate that
      microsurgery, when combined with anti-tuberculosis therapy, is an effective and
      safe method to treat brainstem tuberculous abscesses.

PMID- 28454456
TI  - Pulmonary artery intimal sarcoma misdiagnosed as pulmonary embolism: A case
      report.
AB  - Intimal sarcoma of the pulmonary artery is rare, but false diagnosis of this
      sarcoma as pulmonary embolism is not infrequent. The present study reports a case
      of pulmonary artery intimal sarcoma misdiagnosed as pulmonary artery embolism in
      a 37-year-old female patient. The patient was admitted to the cardiac intensive
      care unit of Guangdong General Hospital (Guangzhou, China) with the complaint of
      progressive exertional dyspnea over the past two years. Multi-slice spiral
      computed tomography, transthoracic echocardiography, right-heart catheterization
      and cardiac magnetic resonance imaging revealed mimicking severe pulmonary
      embolism in the pulmonary trunk and right pulmonary artery, with symptoms
      including chest pain, cough and breathing difficulties. In addition, positron
      emission tomography-computed tomography results did not identify increased 18F
      fluorodeoxyglucose uptake and failed to distinguish whether the mass was a
      thrombus or a malignancy. The patient was diagnosed with pulmonary embolism and a
      subcutaneous injection of 5,000 AxaIU enoxaparin sodium (100 AXAIU/kg) was
      administered every 12 h, but no improvement was achieved after 5 days of
      treatment. Finally, pulmonary endarterectomy was performed to relieve the
      worsening clinical symptoms. The clinicopathological diagnosis was pulmonary
      artery intimal sarcoma with poor clinical outcome. For this type of tumor with
      fatal prognosis, early and correct diagnosis may lead to appropriate intervention
      and prolong survival.

PMID- 28454457
TI  - Detection of circulating tumor cells in patients with non-small cell lung cancer
      using a size-based platform.
AB  - The detection of circulating tumor cells (CTCs) is limited by the rarity of these
      cells in the peripheral blood of patients with cancer. Understanding tumor
      biology may be useful in the development of novel therapeutic strategies for
      patients with lung cancer. The present study evaluated a novel size-based
      filtration platform for enriching CTCs from patients with lung cancer. Blood
      samples were obtained from 82 patients with lung cancer for CTC analysis. CTC
      enrichment by size-based filtration was performed on 5-ml blood samples. The
      collected cells were detected by immunofluorescence using monoclonal anti-human
      antibodies against protein tyrosine phosphatase, receptor type C (CD45) and
      epithelial cell adhesion molecule (EpCAM; an epithelial cell marker), as well as
      a DAPI nucleic acid stain. CTCs were detected in 57 patients (69.5%) using the
      size-based filtration platform. The mean CTC counts, defined as the number of
      cells with DAPI-positive, CD45-negative and EpCAM-positive staining, were 1.48+/
      1.71 per 5 ml blood for the 66 stage I-III patients and 8.00+/-9.95 per 5 ml
      blood for the 16 stage IV patients. The presence of >=1 CTCs per 5-ml blood
      sample was significantly associated with pathological stage (stage IV vs. stage I
      III, P=0.009), but not with patient age or gender, tumor histology, tumor size or
      lymphovascular invasion. The mean CTC count of healthy donors was 0.25+/-0.55 per
      5 ml blood. In summary, CTCs from the blood of patients with lung cancer were
      enriched using a size-based filtration platform and immunofluorescent staining
      with DAPI, CD45 and EpCAM. The CTC counts of patients with stage IV cancer were
      higher than those of patients with stages I-III cancer. These results suggest
      that this novel platform may be a useful tool for determining the prognosis of
      patients with lung cancer.

PMID- 28454458
TI  - Survivin downregulation using siRNA nanoliposomes inhibits cell proliferation and
      promotes the apoptosis of MHCC-97H hepatic cancer cells: An in vitro and in vivo
      study.
AB  - At present, survivin is one of the most cancer-specific proteins that has been
      identified. The present study aimed to investigate the antitumor effects of novel
      survivin small interfering RNA (siRNA) nanoliposomes targeting survivin in human
      hepatocellular carcinoma MHCC-97H cells and xenograft mouse models. Survivin
      targeted siRNA nanoliposomes were prepared and transfected into MHCC-97H cells
      and MHCC-97H-bearing nude mice. Survivin expression was analyzed using reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) and western
      blotting. Cell viability was analyzed using an MTT assay and apoptosis was
      evaluated using Hoechst and Annexin V-fluorescein isothiocyanate/propidium iodide
      staining. Tumor growth in MHCC-97H-bearing mice was monitored following treatment
      and tumor samples were obtained for survivin expression analysis using RT-qPCR,
      western blotting and immunohistochemistry staining. Survivin expression levels
      were significantly downregulated by nanoliposome-mediated survivin siRNA delivery
      and this was associated with a significant inhibition of cell growth and an
      increase in the apoptosis of MHCC-97H cells. Downregulation of survivin
      expression using survivin siRNA nanoliposomes inhibited tumor growth in the MHCC
      97H xenograft models without significant treatment-associated toxicity.
      Therefore, a cationic nanoliposome-based survivin siRNA delivery system was
      constructed and demonstrated to be efficient for survivin siRNA delivery in in
      vitro and in vivo studies. These results demonstrate that survivin downregulation
      was able to significantly attenuate cell proliferation and induce the apoptosis
      of MHCC-97H cells, as well as inhibit tumor cell growth in MHCC-97H xenograft
      models, indicating that survivin suppression using siRNA may contribute to the
      inhibition of tumor development by suppressing cell proliferation and promoting
      apoptosis.

PMID- 28454459
TI  - Expression of CXCL12 and its receptor CXCR4 in patients with adenomyosis.
AB  - The aim of the present study was to investigate the role of chemokine (C-X-C
      motif) ligand 12 (CXCL12) and its receptor, chemokine (C-X-C motif) receptor 4
      (CXCR4) in the pathogenesis of adenomyosis (AD). Immunohistochemistry and reverse
      transcription-quantitative polymerase chain reaction analysis were used to
      measure the protein and mRNA expression of CXCL12 and CXCR4 in eutopic
      endometrial and ectopic foci tissue samples. Samples from a total of 36 patients
      with AD (study group) were compared with endometrial tissue samples from 33
      patients who underwent uterine fibroids surgery (control group) during the same
      period. All data are presented as the mean +/- standard deviation and were
      analyzed with SPSS software (version 16.0). Analysis of variance was used for
      between group analysis and pairwise comparison was performed using Fisher's least
      significant difference post hoc test. The results of the present study revealed
      that CXCL12 and CXCR4 protein expression was significantly increased in ectopic
      foci tissue compared with eutopic endometrial tissue samples from patients with
      AD. CXCL12 and CXCR4 protein expression in ectopic foci and eutopic endometrial
      tissue samples were significantly increased compared with the control group
      (P<0.05 for between group comparisons). No significant differences were
      identified in CXCL12 and CXCR4 protein expression between the proliferative and
      secretory phases within each group. Furthermore, CXCL12 and CXCR4 mRNA expression
      was significantly increased in ectopic foci tissue and eutopic endometrial tissue
      compared with the control group (P<0.05 for between group comparisons). CXCL12
      mRNA expression was markedly increased in ectopic foci tissue compared with
      eutopic endometrial tissue of patients with AD. The expression of CXCR4 mRNA was
      significantly increased in eutopic endometrial tissue compared with ectopic foci
      tissue and the control group (P<0.05 for between group comparisons). No
      significant differences were identified in CXCL12 and CXCR4 mRNA expression
      between proliferative and secretory phase within each group. In conclusion,
      CXCL12 and CXCR4 may induce the ectopia, and promote the spread and localized
      growth of endometrial cells in the development of AD.

PMID- 28454460
TI  - Melatonin treatment induces apoptosis through regulating the nuclear factor
      kappaB and mitogen-activated protein kinase signaling pathways in human gastric
      cancer SGC7901 cells.
AB  - Melatonin, which is synthesized by the pineal gland and released into the blood,
      exhibits antitumor properties. However, the mechanisms underlying these effects,
      particularly in stomach cancer, remain unknown. In the present study, the effect
      of melatonin on the nuclear factor (NF)-kappaB signaling pathway and the mitogen
      activated protein kinase signaling pathway, involving p38 and c-Jun-N-terminal
      kinase (JNK), were investigated in SGC7901 gastric cancer cells. In addition, the
      effect of melatonin on the survival, migration and apoptosis of these cells was
      investigated in vitro in order to evaluate the use of melatonin for the treatment
      of gastric cancer. The results of the present study revealed that melatonin
      decreased the viability and migration of SGC7901 cells. Furthermore, melatonin
      induced apoptosis. Melatonin was identified to elevate the expression levels of
      phosphorylated (p)-p38 and p-JNK protein, and decrease the expression level of
      nucleic p-p65. These results suggest that the protein levels of p65, p38 and JNK
      are associated with the survival of SGC7901 cells following treatment with
      melatonin. The optimal concentration of melatonin was demonstrated to be 2 mM,
      which significantly induced apoptosis following a 24 h treatment period. These
      findings suggest that conflicting growth signals in cells may inhibit the
      efficacy of melatonin in the treatment of gastric cancer. Therefore, adjunct
      therapy would be required to improve the efficacy of melatonin in the treatment
      of cancer.

PMID- 28454461
TI  - Prognostic value of MLH1 promoter methylation in male patients with esophageal
      squamous cell carcinoma.
AB  - The DNA mismatch repair (MMR) gene MutL homolog 1 (MLH1) is critical for the
      maintenance of genomic integrity. Methylation of the MLH1 gene promoter was
      identified as a prognostic marker for numerous types of cancer including
      glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to
      determine whether MLH1 promoter methylation was associated with survival in male
      patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin
      embedded ESCC tissues were collected from 87 male patients. MLH1 promoter
      methylation was assessed using the methylation-specific polymerase chain reaction
      approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate
      the association between MLH1 promoter methylation and overall survival (OS) in
      patients with ESCC. Cox regression analysis was used to obtain crude and
      multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present
      study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of
      male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1
      promoter hypermethylation was significantly associated with poorer prognosis in
      patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1
      promoter hypermethylation was an independent predictor of poor OS in male
      patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter
      hypermethylation may be a predictor of prognosis in male patients with ESCC.

PMID- 28454462
TI  - Effects of irradiation on radioresistance, HOTAIR and epithelial-mesenchymal
      transition/cancer stem cell marker expression in esophageal squamous cell
      carcinoma.
AB  - Radiotherapy is a common therapeutic strategy used to treat esophageal squamous
      cell carcinoma (ESCC). However, tumor cells often develop radioresistance,
      thereby reducing treatment efficacy. Here, we aimed to identify the mechanisms
      through which ESCC cells develop radioresistance and identify associated
      biomarkers. Eca109 cells were exposed to repeated radiation at 2 Gy/fraction for
      a total dose of 60 Gy (Eca109R60/2Gy cells). MTT and colony formation assays were
      performed to measure cell proliferation and compare the radiation biology
      parameters of Eca109 and Eca109R60/2Gy cells. Cell cycle distributions and
      apoptosis were assessed by flow cytometry. Reverse transcription-quantitative
      polymerase chain reaction and western blotting were employed to analyze the
      expression of HOX transcript antisense RNA (HOTAIR), in addition to biomarkers of
      the epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs).
      Eca109R60/2Gy cells exhibited increased cell proliferation and clone formation,
      with significantly higher radiobiological parameters compared with the parental
      Eca109 cells. The Eca109R60/2Gy cells also exhibited significantly decreased
      accumulation in G2 phase and increased accumulation in S phase. Additionally, the
      apoptosis rate was significantly lower in Eca109R60/2Gy cells than in parental
      Eca109 cells. Finally, HOTAIR expression levels and SNAI1 and beta-catenin mRNA
      and protein expression levels were significantly higher, whereas E-cadherin
      levels were significantly lower in Eca109R60/2Gy cells than in Eca109 cells.
      Therefore, our findings demonstrated that radioresistance was affected by the
      expression of HOTAIR and biomarkers of the EMT and CSCs.

PMID- 28454463
TI  - Reduced EBP50 expression levels are correlated with unfavorable
      clinicopathological features of extrahepatic bile duct carcinoma and promote the
      proliferation and migration of QBC939 cells.
AB  - The present study aimed to clarify the association between ezrin-radixin-moesin
      binding phosphoprotein-50 (EBP50) expression level and the tumor phenotype and
      clinicopathological features of extrahepatic bile duct carcinoma. Tissue samples
      from patients with extrahepatic bile duct carcinoma (54 cases) and patients with
      normal bile duct epithelia from gallbladder of cholecystitis (20 cases) were
      collected, and immunohistochemical staining was used to detect the expression
      levels of EBP50 in these tissues. In addition, small interfering (si)RNA-EBP50
      was used to knock down the expression of EBP50 in the QBC939 human
      cholangiocarcinoma (CC) cell line. The effect of EBP50 expression on QBC939 cell
      proliferation and migration was analyzed using the Cell Counting kit-8 and wound
      healing assays, respectively. EBP50 expression was significantly downregulated in
      CC tissue samples (P<0.01), with low EBP50 expression levels positively
      correlated with a high pathological stage and a poor differentiation degree
      (P<0.01 and P<0.001, respectively). EBP50 expression in QBC939 cells was knocked
      down by <=80% using siRNA-EBP50, and EBP50 knockdown significantly promoted
      QBC939 cell proliferation, as compared with the vector control cells (P=0.04).
      EBP50 knockdown also significantly enhanced the wound healing ability of QBC939
      cells (P=0.02). These results demonstrated that EBP50 expression levels are
      significantly correlated with a malignant phenotype in patients with CC, and
      decreased expression levels of EBP50 may promote CC cell proliferation and
      migration. These findings provide insight into novel potential diagnostic and
      therapeutic approaches for patients with CC.

PMID- 28454464
TI  - Metastasis from a primary hepatic angiosarcoma to the colon: A case report and
      literature review.
AB  - Primary hepatic angiosarcoma is a rare type of tumor with a poor prognosis. To
      the best of our knowledge, curative surgery of a metastatic gastrointestinal
      angiosarcoma from a hepatic angiosarcoma has not been reported previously. In the
      present report, a case of colonic metastasis from a primary hepatic angiosarcoma
      is discussed. A rapidly growing mass was identified in the liver of an 84-year
      old Japanese male who underwent a subsegmentectomy of the liver. Microscopic
      examination determined that the mass was an angiosarcoma composed of sheets of
      spindle cells. Immunohistochemical studies confirmed the diagnosis with positive
      CD31 staining, which indicated the endothelial nature of the malignancy. A total
      of 14 months following surgery, the patient did not exhibit any symptoms;
      however, follow-up positron emission tomography and computed tomography images
      revealed a mass in the cecum. The patient underwent an ileocolectomy, and the
      microscopic and immunohistochemical findings indicated that the mass was a
      metastasized colorectal angiosarcoma. At a 4-year post-surgery follow-up
      appointment the patient was alive with no evidence of recurrence or metastasis.

PMID- 28454465
TI  - Microarray based analysis of gene regulation by mesenchymal stem cells in breast
      cancer.
AB  - Breast cancer is one of the most common malignant tumors with a high case
      fatality rate among women. The present study aimed to investigate the effects of
      mesenchymal stem cells (MSCs) on breast cancer by exploring the potential
      underlying molecular mechanisms. The expression profile of GSE43306, which refers
      to MDA-MB-231 cells with or without a 1:1 ratio of MSCs, was downloaded from Gene
      Expression Omnibus database for differentially expressed gene (DEG) screening.
      The Database for Annotation, Visualization and Integrated Discovery was used for
      gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
      enrichment analysis for DEGs. The protein-protein interactional (PPI) network of
      DEGs was constructed using the Search Tool for the Retrieval of Interacting
      Genes/Proteins. The data was subsequently analyzed using molecular complex
      detection for sub-network mining of modules. Finally, DEGs in modules were
      analyzed using GO and KEGG pathway enrichment analyses. A total of 291 DEGs
      including 193 upregulated and 98 downregulated DEGs were obtained. Upregulated
      DEGs were primarily enriched in pathways including response to wounding
      (P=5.92*10-7), inflammatory response (P=5.92*10-4) and defense response
      (P=1.20*10-2), whereas downregulated DEGs were enriched in pathways including the
      cell cycle (P=7.13*10-4), mitotic cell cycle (P=6.81*10-3) and M phase (P=1.72
      *10-2). The PPI network, which contained 156 nodes and 289 edges, was
      constructed, and Fos was the hub node with the degree of 29. A total of 3 modules
      were mined from the PPI network. In total, 14 DEGs in module A were primarily
      enriched in GO terms, including response to wounding (P=4.77*10-6), wounding
      healing (P=6.25*10-7) and coagulation (P=1.13 *10-7), and these DEGs were also
      enriched in 1 KEGG pathway (complement and coagulation cascades; P=0.0036).
      Therefore, MSCs were demonstrated to exhibit potentially beneficial effects for
      breast cancer therapy. In addition, the screened DEGs, particularly in PPI
      network modules, including FN1, CD44, NGF, SERPINE1 and CCNA2, may be the
      potential target genes of MSC therapy for breast cancer.

PMID- 28454466
TI  - Identification of molecular characteristics induced by radiotherapy in rectal
      cancer based on microarray data.
AB  - The present study aimed to reveal the molecular characteristics induced by
      radiotherapy in rectal cancer at the transcriptome level. Microarray data (ID,
      GSE26027) downloaded from the Gene Expression Omnibus database were re-analyzed
      to identify differentially expressed genes (DEGs) between rectal cancer tissues
      during and prior to radiotherapy. The DEGs were then inputted into the database
      for annotation, visualization and integrated discovery, an online tool to perform
      enrichment analyses, and into the search tool for the retrieval of interacting
      genes/proteins database to identify protein-protein interactions (PPIs).
      Subsequently, a PPI network was constructed, which was screened for densely
      connected modules. Furthermore, protein domain enrichment analysis was performed.
      In total, 690 DEGs, including 179 upregulated and 511 downregulated DEGs, were
      found in rectal cancer tissues during and prior to radiotherapy. The upregulated
      DEGs were significantly enriched in 'positive regulation of transport' and
      'regulation of cardiac muscle contraction', while the downregulated DEGs were
      most markedly enriched in 'cell migration', 'cell-cell signaling', 'extracellular
      matrix organization' and 'blood vessel development', including prostaglandin
      endoperoxide synthase 2, transforming growth factor beta-induced, 68 kDa
      endothelin receptor type A, brain-derived neurotrophic factor, TIMP
      metallopeptidase inhibitor 1, and serpin family E member 1, which were the top 6
      hub nodes in the PPI network. Furthermore, 2 protein domains were significantly
      enriched by PPI modules, including: The collagen triple helix repeat (CTHR)
      family members collagen type (COL) 5A2, COL9A3, COL6A3, COL21A1, COL5A3, COL11A1,
      COL7A1 and CTHR-containing-1; and the olfactory receptor family (OR) members
      OR7E24, OR7A17, OR6A2, OR1F1, OR10H3 and OR7A10. A total of 7 upregulated DEGs
      were characterized as tumor suppressor genes, and 8 downregulated DEGs were
      characterized as oncogenes. The biological processes or protein domains enriched
      by upregulated or downregulated DEGs may improve the understanding of molecular
      characteristics in response to radiotherapy.

PMID- 28454467
TI  - Investigation of differentially-expressed microRNAs and genes in cervical cancer
      using an integrated bioinformatics analysis.
AB  - Cervical cancer is one of the most common types of cancer among women worldwide.
      In order to identify the microRNAs (miRNAs/miRs) and mRNAs associated with the
      carcinogenesis of cervical cancer, and to investigate the molecular mechanisms of
      cervical cancer, an miRNA microarray, GSE30656, and 3 mRNA microarrays, GSE63514,
      GSE39001 and GSE9750, for cervical cancer were retrieved from Gene Expression
      Omnibus. These datasets were analyzed in order to obtain differentially-expressed
      genes (DEGs) and miRNAs using the GEO2R tool. Gene Ontology (GO) and pathway
      enrichment analysis for DEGs were performed using the Database for Annotation,
      Visualization and Integrated Discovery. Protein-protein interaction (PPI)
      analysis for DEGs was conducted using The Search Tool for the Retrieval of
      Interacting Genes software and visualized using Cytoscape, followed by hub gene
      identification, and biological process and pathway enrichment analysis of the
      module selected from the PPI network using the Molecular Complex Detection
      plugin. In addition, miRecords was applied to predict the targets of
      differentially-expressed miRNAs. A total of 44 DEGs and 15 differentially
      expressed miRNAs were identified. These DEGs were mainly enriched in GO terms
      associated with the cell cycle. In the PPI network, cyclin-dependent kinase 1,
      topoisomerase DNA IIalpha, aurora kinase A (AURKA) and minichromosome maintenance
      complex component 2 (MCM2) had higher degrees of connectivity. A significant
      module was detected from the PPI network. AURKA, MCM2 and kinesin family member
      20A exhibited higher degrees in this module, while the genes in the module were
      mainly involved in the cell cycle and the DNA replication pathway. In addition,
      estrogen receptor 1 was predicted as the potential target of 13 miRNAs. A total
      of 10 DEGs were identified as potential targets of miR-203. In conclusion, the
      results indicated that microarray dataset analysis may provide a useful method
      for the identification of key genes and patterns to successfully identify
      determinants of the carcinogenesis of cervical cancer. The functional studies of
      candidate genes and miRNAs from these databases may lead to an increased
      understanding of the development of cervical cancer.

PMID- 28454468
TI  - Ethanolic extract of Thevetia peruviana flowers enhances TNF-alpha and TRAIL
      induced apoptosis of human cervical cancer cells via intrinsic and extrinsic
      pathways.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and TNF-related apoptosis-inducing ligand
      (TRAIL) are promising candidates for cancer treatment due to their ability to
      induce apoptosis through death receptor stimulation. However, their usage may be
      limited due to the resistance of cancer cells to TNF-alpha- and TRAIL-induced
      apoptosis. Currently, there is interest in screening for natural products that
      can sensitize cancer cells to TNF-alpha- and TRAIL-induced apoptosis for their
      use in combination with TNF-alpha or TRAIL. It was previously reported that the
      bark extract of Thevetia peruviana showed a reversal effect on TRAIL-resistance
      in human gastric adenocarcinoma cell lines. In the present study, the effects of
      the ethanolic extract of T. peruviana flowers on TNF-alpha- and TRAIL-induced
      apoptosis of human cervical cancer HeLa cells were investigated in vitro by
      determining cell viability and apoptosis using a WST-1 cell proliferation assay
      and immunoblot analysis, respectively. The ethanolic extract of T. peruviana
      flowers promoted TNF-alpha and TRAIL-mediated cell death through the activation
      of the caspase cascade, poly(ADP-ribose) polymerase and BH3-interacting domain
      death agonist cleavage. Combined treatment using the extract plus TNF-alpha
      resulted in downregulation of anti-apoptotic protein, including myeloid cell
      leukemia sequence-1, B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of
      apoptosis protein and survivin, while the combined treatment with TRAIL
      downregulated Bcl-XL. Thus, the ethanolic extract of T. peruviana flowers has
      potential in sensitizing the TNF-alpha- and TRAIL-induced apoptosis of HeLa cells
      via the intrinsic and extrinsic pathways.

PMID- 28454469
TI  - Regulation of cytotoxicity and apoptosis-associated pathways contributes to the
      enhancement of efficacy of cisplatin by baicalein adjuvant in human A549 lung
      cancer cells.
AB  - Scutellaria baicalensis (SB; Chinese name, huangqin) is widely used in Chinese
      medicine as a traditional adjuvant in the chemotherapy of lung and liver cancer.
      Baicalein is one of the bioactive flavonoid components isolated from the root of
      SB. The present study aimed to observe the effect of baicalein, in combination
      with platin-based systemic chemotherapy (cisplatin), on cytotoxicity and
      apoptosis of human A549 lung cancer cells. The cell cultures were treated with
      baicalein, cisplatin, or a combination of the two. Cell viability and
      cytotoxicity was assayed by XTT, and cell apoptosis was measured by flow
      cytometry. The apoptosis-associated proteins were detected by western blot
      analysis. The cytokines in the culture supernatant were detected by ELISA. The
      present study revealed that cisplatin and the baicalein-cisplatin combination
      inhibited viability and promoted cytotoxicity of A549 cells. Cisplatin, baicalein
      and baicalein-cisplatin combination treatments were effective in the promotion of
      apoptosis of A549 cells. Baicalein and baicalein-cisplatin combination treatments
      also inhibited B cell lymphoma-2 (Bcl-2) and increased Bcl-2-associated X protein
      (Bax) expression. Additionally, cisplatin, baicalein and the baicalein-cisplatin
      combination promoted caspase-3 expression. Furthermore, the baicalein-cisplatin
      combination suppressed the secretion of interleukin-6, and baicalein and the
      combination of baicalein cisplatin decreased the secretion of tumor necrosis
      factor-alpha of A549 cells. The present study concluded that baicalein combined
      with cisplatin induced cytotoxicity and apoptosis of A549 cells, and such
      activity may be associated with the regulation of Bcl-2, Bax and caspase-3,
      indicating a promising alternative method for lung cancer.

PMID- 28454470
TI  - Terrein performs antitumor functions on esophageal cancer cells by inhibiting
      cell proliferation and synergistic interaction with cisplatin.
AB  - Terrein is a bioactive fungal metabolite isolated from Aspergillus terreus.
      Besides being a melanogenesis inhibitor, previous studies have revealed that
      terrein has antiproliferative effects on a number of types of cancer tumors. In
      the present study, the inhibitory effect of terrein on esophageal cancer was
      evaluated and the possible underlying mechanisms were investigated. The results
      revealed that terrein inhibited the proliferation of Eca109 esophageal cancer
      cells in a dose- and time-dependent manner. Mechanistically, terrein treatment
      led to the G2/M phase arrest of Eca109 cells by indirectly regulating cyclin B1
      and phosphorylating the cell division cycle protein 2 genes. Notably, terrein
      exhibited a synergistic effect on Eca109 cells when combined with cisplatin,
      which is a commonly used chemotherapeutic drug. Taken together, these findings
      indicate that terrein suppresses the proliferation of esophageal cancer cells,
      and may prove to be a novel therapeutic approach for the treatment of esophageal
      cancer via inhibiting the proliferation of cancer cells.

PMID- 28454471
TI  - Downregulation of FKBP14 by RNA interference inhibits the proliferation, adhesion
      and invasion of gastric cancer cells.
AB  - FK506 binding protein (FBBP) 14 belongs to the family of FKBPs. Altered
      expression of FKBPs are observed in several malignancies. The present study aimed
      to explore the expression and biological function of FKBP14 in gastric cancer.
      FKBP14 expression levels in 40 gastric cancer samples and matched control samples
      were evaluated using quantitative polymerase chain reaction. Cell proliferation
      was evaluated using Cell Counting kit-8 assay. A cell adhesion and a Transwell
      assay were performed to detect cell adhesion and invasion. Protein expression was
      determined using western blot analysis. It was found that FKBP14 expression in
      gastric cancer tissues was elevated compared with normal tissues. Silencing of
      FKBP14 expression in the gastric cancer MKN-45 and AGS cell lines, which have a
      higher expression level of FKBP14 compared with four other gastric cancer cell
      lines, significantly inhibited cellular proliferation, adhesion and invasion. In
      addition, the protein levels of proliferating cell nuclear antigen, matrix
      metalloproteinase 2 and the epithelial-mesenchymal-transition (EMT) markers beta
      catenin, Snail1 and Twist were repressed in gastric cancer cells with FKBP14
      silenced. In conclusion, FKBP14 may act as an oncogene by suppressing cellular
      proliferation, adhesion and invasion and EMT in gastric carcinogenesis. FKBP14
      may be a diagnosis marker and potential therapeutic target in gastric cancer.

PMID- 28454472
TI  - Hsp90 inhibitor SY-016 induces G2/M arrest and apoptosis in paclitaxel-resistant
      human ovarian cancer cells.
AB  - The aim of the present study was to evaluate the in vitro effect of a heat shock
      protein (Hsp)90 inhibitor, SY-016, on the paclitaxel (PTX)-resistant human
      ovarian cancer cell line OVCAR-3PTX, and explore its mechanism of apoptosis. In
      the present study, SY-016 was used in combination with PTX to determine its
      effect on the cell proliferation and apoptosis of OVCAR-3PTX cells. The drug
      resistant tumor cells were established in vitro by stepwise sequential exposure
      to increasing concentrations of PTX. The cell viability and cell cycle
      distribution were measured by MTT assay and flow cytometric analysis,
      respectively. The induction of apoptosis was measured by caspase-3 activity, DNA
      fragmentation and western blot analyses. The cell viability significantly
      decreased following treatment with PTX and SY-016 as compared with either drug
      alone. The DNA fragmentation assay revealed an induction of apoptosis. The
      results from the flow cytometric analysis revealed an increase in the percentage
      of cells in the G2/M phase. Downregulation of B-cell lymphoma (Bcl)-2, X-linked
      inhibitor of apoptosis protein, survivin, Akt, nuclear factor-kappaB and cyclin
      dependent kinase 4, as well as upregulation of Bcl-2-associated X protein, were
      observed. SY-016 may contribute to the induction of apoptosis in OVCAR-3PTX
      cells. These results suggest that SY-016 in combination with PTX may be a
      beneficial chemotherapeutic strategy, particularly in patients with tumors
      refractory to PTX.

PMID- 28454473
TI  - Methylation pattern of preferentially expressed antigen of melanoma in acute
      myeloid leukemia and myelodysplastic syndromes.
AB  - Preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen,
      is overexpressed in a variety of hematologic malignancies with a great variation
      in expression. The majority of patients with acute myeloid leukemia (AML) 1-eight
      twenty one (ETO)+ AML and a certain number of myelodysplastic syndromes (MDS)
      have an abnormally high increase in PRAME expression level. The landscape of
      PRAME methylation requires evaluation in order to determine the most relevant
      sites and the exact association of its methylation with expression level and type
      of disease. In the present study, bone marrow samples collected from 8 AML1-ETO+
      AML, 4 MDS, 3 AML1-ETO- AML and 2 normal volunteers underwent bisulfate
      sequencing to analyze the methylation status of all four 5'-C-phosphate-G-3'
      (CpG) regions within the entire PRAME gene. The median PRAME transcript level of
      15 patients was 204.5% (range, 0.02-710.3%). PRAME transcript levels were
      inversely associated with the degree of methylation of the -389 to -146 CpG sites
      (r=-0.69; P=0.002) in the 3' part of the promoter region and the +132 to +363 CpG
      sites (r=-0.69; P=0.006) in the exon 1b region. However, not every sample
      strictly followed this correlation: Certain samples with high degrees of
      methylation demonstrated abnormally high expression levels, and vice versa. The
      methylation ratios of CpG sites in exon 1a were low for all samples (range, 0.0
      13.8%), and those in exon 2 were similar in 16 samples (range, 72.4-93.4%), with
      the exception of one patient with high expression (425.2%) and significantly low
      degree of methylation in the PRAME gene (22.2%). MDS patients revealed similar
      methylation ratios in the 3' section of the promoter region, but tended to have
      lower methylation ratios in the exon 1b region (P=0.62 and P=0.09, respectively)
      compared with those observed in AML1-ETO+ patients with AML and similar degree of
      PRAME overexpression. Therefore, the hypomethylation of CpG sites in the 3' part
      of the promoter region and in exon 1b was typically found with PRAME
      overexpression in AML and MDS. Methylation of other CpG islands, epigenetic and
      genetic mechanisms, and type of disease may also be involved.

PMID- 28454474
TI  - Incidence trends in high-grade primary brain tumors in males and females.
AB  - The focus of the present review is to investigate whether there is a variation in
      the incidence rates between male and female patients with high-grade primary
      brain tumors and if there are altered incidence rates associated with the time at
      which they were diagnosed. Previous studies identified in internationally peer
      reviewed journals were identified using a systematic search of the PubMed
      database. Due to the difficulties in data interpretation, studies that
      exclusively included patient data classified prior to the 2nd edition of the
      World Health Organization histological classification system of brain tumors were
      excluded. The overall incidence rates and incidence trends of male and female
      patients were analyzed separately. The mean age-adjusted overall incidence rate
      in the male population was 1.27 per 100,000 compared with 0.89 per 100,000 in the
      female population. The variance between the two genders differed and a Wilcoxon
      rank-sum test indicated that there was no significant difference in the incidence
      rate of high-grade primary brain tumors between males and females (P=0.3658).
      Furthermore, there was no significant difference in incidence rate trend between
      1996-2004 and 2005-2010 for male or female populations (P=0.101 and P=0.472,
      respectively). The results from the present systematic review did not demonstrate
      a significant difference in incidence rate between the two genders. Therefore,
      the results from the current study are considered to be preliminary and further
      studies are required to elucidate this issue.

PMID- 28454476
TI  - PARP inhibition sensitizes endometrial cancer cells to paclitaxel-induced
      apoptosis.
AB  - PARP inhibitors are used in the treatment of gynecological malignancies and it
      has been demonstrated in preclinical studies that PARP inhibition sensitizes
      cancer cells to cytotoxic agents. In the present study, PARP expression was
      detected in different endometrial cancer cell lines by western blot analysis, and
      PARP activity was measured using an enzymatic assay. In addition, the endometrial
      cancer cell lines were treated with paclitaxel or carboplatin in combination with
      the PARP inhibitor PJ34 prior to a cell viability assay and apoptotic nuclei
      measurement. PARP protein was detected in all four cell lines examined, although
      its activity varied between the cell lines. Treatment with PJ34 in combination
      with paclitaxel decreased endometrial cancer cell viability compared with
      treatment with paclitaxel alone. These results indicate that the inhibition of
      PARP with PJ34 sensitizes endometrial cancer cells to cytotoxic treatment with
      paclitaxel.

PMID- 28454475
TI  - Oridonin induces G2/M cell cycle arrest and apoptosis via the PI3K/Akt signaling
      pathway in hormone-independent prostate cancer cells.
AB  - Oridonin is an active constituent isolated from the traditional Chinese herb
      Rabdosia rubescens, which exerts antitumor effects in experimental and clinical
      settings. However, its antitumor effects and underlying mechanisms on prostate
      cancer cells have not yet been clearly identified. In the present study, the
      androgen-independent prostate cancer PC3 and DU145 cell lines were used as models
      to investigate the effects and possible mechanisms of oridonin on cellular
      proliferation and apoptosis. Results demonstrated that oridonin inhibited
      cellular proliferation, and was able to significantly induce G2/M cell cycle
      arrest and apoptosis. Detailed signaling pathway analysis by western blotting
      demonstrated that the expression levels of p53 and p21 were upregulated, whereas
      the expression of cyclin-dependent kinase 1 was downregulated following oridonin
      treatment, which led to cell cycle arrest in the G2/M phase. Oridonin also
      upregulated the proteolytic cleaved forms of caspase-3, caspase-9 and poly (ADP
      ribose) polymerase. Furthermore, the protein expression levels of B-cell lymphoma
      2 were decreased and those of Bcl-2-associated X protein were increased following
      oridonin treatment. In addition, oridonin treatment significantly inhibited the
      expression of phosphoiniositide-3 kinase (PI3K) p85 subunit and the
      phosphorylation of Akt. The downstream gene murine double minute 2 was also
      downregulated, which may contribute to the elevated expression of p53 following
      oridonin treatment. In conclusion, the results of the present study suggested
      that oridonin is able to inactivate the PI3K/Akt pathway and activate p53
      pathways in prostate cancer cells, resulting in the suppression of proliferation
      and the induction of caspase-mediated apoptosis.

PMID- 28454477
TI  - In Situ Analysis of Oxygen Vacancies and Band Alignment in HfO2/TiN Structure for
      CMOS Applications.
AB  - The density of oxygen vacancies characterization in high-k/metal gate is
      significant for semiconductor device fabrication. In this work, a new approach
      was demonstrated to detect the density of oxygen vacancies by in situ x-ray
      photoelectron spectroscopy (XPS) and ultraviolet photoelectron spectroscopy (UPS)
      measurement. Moreover, the band alignment of the structure with optical band gap
      measured by spectroscopic ellipsometry (SE) and valence band offset by UPS were
      reported. The specific areal density of oxygen vacancies in high-k dielectric of
      HfO2/TiN was obtained by fitting the experiment data to be 8.202 * 1010cm- 2.
      This study would provide an effective approach to characterize the oxygen
      vacancies based defects which cause threshold voltage shifts and enormous gate
      leakage in modern MOSFET devices.

PMID- 28454478
TI  - Enhanced MRI T 2 Relaxivity in Contrast-Probed Anchor-Free PEGylated Iron Oxide
      Nanoparticles.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs, ~11-nm cores) were PEGylated
      without anchoring groups and studied as efficient MRI T 2 contrast agents (CAs).
      The ether group of PEG is efficiently and directly linked to the positively
      charged surface of SPIONs, and mediated through a dipole-cation covalent
      interaction. Anchor-free PEG-SPIONs exhibit a spin-spin relaxivity of 123 +/- 6
      mM-1s-1, which is higher than those of PEG-SPIONs anchored with intermediate
      biomolecules, iron oxide nanoworms, or Feridex. They do not induce a toxic
      response for Fe concentrations below 2.5 mM, as tested on four different cell
      lines with and without an external magnetic field. Magnetic resonance phantom
      imaging studies show that anchor-free PEG-SPIONs produce a significant contrast
      in the range of 0.1-0.4 [Fe] mM. Our findings reveal that the PEG molecules
      attached to the cores immobilize water molecules in large regions of ~85 nm,
      which would lead to blood half-life of a few tens of minutes. This piece of
      research represents a step forward in the development of next-generation CAs for
      nascent-stage cancer detection. Contrast-probed anchor-free PEGylated iron oxide
      contrast agent.

PMID- 28454479
TI  - In Situ Immobilization on the Silica Gel Surface and Adsorption Capacity of
      Poly[N-(4-carboxyphenyl)methacrylamide] on Toxic Metal Ions.
AB  - In situ immobilization of poly[N-(4-carboxyphenyl)methacrylamide] has been
      performed on silica gel surface. Infrared (IR) and mass spectroscopies as well as
      thermogravimetry (TG) analysis have been used to elucidate the structure of
      immobilized polymer. An adsorption capacity of the synthesized composite towards
      Cu(II), Pb(II), Mn(II), Fe(III), Co(II), and Ni(II) ions has been estimated.
      Adsorption activity to microquantities of Pb(II), Cu(II), and Ni(II) in a neutral
      aqueous medium has been observed.

PMID- 28454480
TI  - Immobilization of pH-sensitive CdTe Quantum Dots in a Poly(acrylate) Hydrogel for
      Microfluidic Applications.
AB  - Microfluidic devices present the basis of modern life sciences and chemical
      information processing. To control the flow and to allow optical readout, a
      reliable sensor material that can be easily utilized for microfluidic systems is
      in demand. Here, we present a new optical readout system for pH sensing based on
      pH sensitive, photoluminescent glutathione capped cadmium telluride quantum dots
      that are covalently immobilized in a poly(acrylate) hydrogel. For an applicable
      pH sensing the generated hybrid material is integrated in a microfluidic sensor
      chip setup. The hybrid material not only allows in situ readout, but also
      possesses valve properties due to the swelling behavior of the poly(acrylate)
      hydrogel. In this work, the swelling property of the hybrid material is utilized
      in a microfluidic valve seat, where a valve opening process is demonstrated by a
      fluid flow change and in situ monitored by photoluminescence quenching. This
      discrete photoluminescence detection (ON/OFF) of the fluid flow change (OFF/ON)
      enables upcoming chemical information processing.

PMID- 28454481
TI  - AlN Surface Passivation of GaN-Based High Electron Mobility Transistors by Plasma
      Enhanced Atomic Layer Deposition.
AB  - We report a low current collapse GaN-based high electron mobility transistor
      (HEMT) with an excellent thermal stability at 150  degrees C. The AlN was grown
      by N2-based plasma enhanced atomic layer deposition (PEALD) and shown a
      refractive index of 1.94 at 633 nm of wavelength. Prior to deposit AlN on III
      nitrides, the H2/NH3 plasma pre-treatment led to remove the native gallium oxide.
      The X-ray photoelectron spectroscopy (XPS) spectroscopy confirmed that the native
      oxide can be effectively decomposed by hydrogen plasma. Following the in situ ALD
      AlN passivation, the surface traps can be eliminated and corresponding to a 22.1%
      of current collapse with quiescent drain bias (V DSQ) at 40 V. Furthermore, the
      high temperature measurement exhibited a shift-free threshold voltage (V th),
      corresponding to a 40.2% of current collapse at 150  degrees C. The thermal
      stable HEMT enabled a breakdown voltage (BV) to 687 V at high temperature,
      promising a good thermal reliability under high power operation.

PMID- 28454482
TI  - Effects of Environmental Factors and Metallic Electrodes on AC Electrical
      Conduction Through DNA Molecule.
AB  - BACKGROUND: Deoxyribonucleic acid (DNA) is one of the best candidate materials
      for various device applications such as in electrodes for rechargeable batteries,
      biosensors, molecular electronics, medical- and biomedical-applications etc.
      Hence, it is worthwhile to examine the mechanism of charge transport in the DNA
      molecule, however, still a question without a clear answer is DNA a molecular
      conducting material (wire), semiconductor, or insulator? The answer, after the
      published data, is still ambiguous without any confirmed and clear scientific
      answer. DNA is found to be always surrounded with different electric charges,
      ions, and dipoles. These surrounding charges and electric barrier(s) due to
      metallic electrodes (as environmental factors (EFs)) play a substantial role when
      measuring the electrical conductivity through lambda-double helix (DNA) molecule
      suspended between metallic electrodes. We found that strong frequency dependence
      of AC-complex conductivity comes from the electrical conduction of EFs. This
      leads to superimposing serious incorrect experimental data to measured ones.
      METHODS: At 1 MHz, we carried out a first control experiment on electrical
      conductivity with and without the presence of DNA molecule. If there are possible
      electrical conduction due to stray ions and contribution of substrate, we will
      detected them. This control experiment revealed that there is an important role
      played by the environmental-charges around DNA molecule and any experiment should
      consider this role. RESULTS AND DISCUSSION: We have succeeded to measure both
      electrical conductivity due to EFs (sigma ENV) and electrical conductivity due to
      DNA molecule (sigma DNA) independently by carrying the measurements at different
      DNA-lengths and subtracting the data. We carried out measurements as a function
      of frequency (f) and temperature (T) in the ranges 0.1 Hz < f < 1 MHz and 288 K <
      T < 343 K. The measured conductivity (sigma MES) portrays a metal-like behavior
      at high frequencies near 1 MHz. However, we found that sigma DNA was far from
      this behavior because the conduction due to EFs superimposes sigma DNA, in
      particular at low frequencies. By measuring the electrical conductivity at
      different lengths: 40, 60, 80, and 100 nm, we have succeeded not only to separate
      the electrical conduction of the DNA molecule from all EFs effects that surround
      the molecule, but also to present accurate values of sigma DNA and the dielectric
      constant of the molecule epsilon'DNA as a function of temperature and frequency.
      Furthermore, in order to explain these data, we present a model describing the
      electrical conduction through DNA molecule: DNA is a classical semiconductor with
      charges, dipoles and ions that result in creation of localized energy-states
      (LESs) in the extended bands and in the energy gap of the DNA molecule.
      CONCLUSIONS: This model explains clearly the mechanism of charge transfer
      mechanism in the DNA, and it sheds light on why the charge transfer through the
      DNA can lead to insulating, semiconducting, or metallic behavior on the same
      time. The model considers charges on DNA, in the extended bands, either could be
      free to move under electric field or localized in potential wells/hills.
      Localization of charges in DNA is an intrinsic structural-property of this
      solitaire molecule. At all temperatures, the expected increase in thermal-induced
      charge is attributed to the delocalization of holes (or/and electrons) in
      potential hills (or/and potential wells) which accurately accounts for the total
      electric and dielectric behavior through DNA molecule. We succeeded to fit the
      experimental data to the proposed model with reasonable magnitudes of potential
      hills/wells that are in the energy range from 0.068 eV.

PMID- 28454483
TI  - Efficient Carrier Injection, Transport, Relaxation, and Recombination Associated
      with a Stronger Carrier Localization and a Low Polarization Effect of Nonpolar m
      plane InGaN/GaN Light-Emitting Diodes.
AB  - Based on time-resolved electroluminescence (TREL) measurement, more efficient
      carrier injection, transport, relaxation, and recombination associated with a
      stronger carrier localization and a low polarization effect in a nonpolar m-plane
      InGaN/GaN light emitting diode (m-LED), compared with those in a polar c-LED, are
      reported. With a higher applied voltage in the c-LED, decreasing response time
      and rising time improve device performance, but a longer recombination time
      degrades luminescence efficiency. By using an m-LED with a stronger carrier
      localization and a low polarization effect, shorter response, rising, and
      recombination times provide more efficient carrier injection, transport,
      relaxation, and recombination. These advantages can be realized for high-power
      and high-speed flash LEDs. In addition, with a weaker carrier localization and a
      polarization effect in the c-LED, the slower radiative and faster nonradiative
      decay rates at a larger applied voltage result in the slower total decay rate and
      the lower luminescence efficiency. For the m-LED at a higher applied voltage, a
      slow decreasing nonradiative decay rate is beneficial to device performance,
      while the more slowly decreasing and overall faster radiative decay rate of the m
      LED than that of the c-LED demonstrates that a stronger carrier localization and
      a reduced polarization effect are efficient for carrier recombination. The
      resulting recombination dynamics are correlated with the device characteristics
      and performance of the c- and m-LEDs.

PMID- 28454485
TI  - Cheminformatics-Based Anticoagulant Study of Traditionally Used Medicinal Plants
AB  - Backgroung: Medicinal plants, as a complementary medicine, have been used to
      treat various diseases since ancient times. These plants have numerous beneficial
      applications and are the source of certain conventional drugs. In diseases such
      as stroke and ischemia, which are caused by several factors, abnormal coagulation
      is an important causative factor. Accordingly, novel and effective therapies such
      as herbal remedies should be practiced to prevent such lethal diseases. Methods:
      Using the available databases such as Google Scholar and PubMed, the previously
      reported anticoagulant compounds and plants possessing anticoagulant activity
      were identified and collected in two separate lists. Next, the fast and cost
      effective cheminformatics methods incorporated in PubChem were applied to detect
      some compounds similar to reported anticoagulants. Subsequently, 15 native
      medical plants of Iran containing the potential anticoagulants were selected. The
      selected plants were purchased and chopped, and the potential compounds were
      extracted by ethanol. Then three concentrations of extracts (1, 10, and 100 ug
      per ml) were made. Finally, anticoagulant effect of the selected plants was
      evaluated by in vitro prothrombin time and activated partial thromboplastin time
      coagulation tests. Results: Among the 15 selected medicinal plants, three plants,
      including Terminalia bellirica (P=0.0019), Astragalus arbusculinus (P=0.0021),
      and Origanum vulgare (P=0.0014) showed a more promising anticoagulant effect in
      comparison to the control. Conclusion: The anticoagulant activity was identified
      for the first time in these three plants. Further in vivo study and mechanism of
      action assay are required to be performed on these three plants, which could be
      suitable candidates for use as natural anticoagulant medicines.

PMID- 28454486
TI  - Binary agonist surface patterns prime platelets for downstream adhesion in
      flowing whole blood.
AB  - As platelets encounter damaged vessels or biomaterials, they interact with a
      complex milieu of surface-bound agonists, from exposed subendothelium to adsorbed
      plasma proteins. It has been shown that an upstream, surface-immobilized agonist
      is capable of priming platelets for enhanced adhesion downstream. In this study,
      binary agonists were integrated into the upstream position of flow cells and the
      platelet priming response was measured by downstream adhesion in flowing whole
      blood. A nonadditive response was observed in which platelets transiently exposed
      to two agonists exhibited greater activation and downstream adhesion than that
      from the sum of either agonist alone. Antibody blocking of one of the two
      upstream agonists eliminated nonadditive activation and downstream adhesion.
      Crosstalk between platelet activation pathways likely led to a synergistic effect
      which created an enhanced activation response in the platelet population. The
      existence of synergy between platelet priming pathways is a concept that has
      broad implications for the field of biomaterials hemocompatibility and platelet
      activity testing.

PMID- 28454487
TI  - Diffusion kurtosis imaging of the liver at 3 Tesla: in vivo comparison to
      standard diffusion-weighted imaging.
AB  - Background Functional techniques like diffusion-weighted imaging (DWI) are
      gaining more and more importance in liver magnetic resonance imaging (MRI).
      Diffusion kurtosis imaging (DKI) is an advanced technique that might help to
      overcome current limitations of DWI. Purpose To evaluate DKI for the
      differentiation of hepatic lesions in comparison to conventional DWI at 3 Tesla.
      Material and Methods Fifty-six consecutive patients were examined using a routine
      abdominal MR protocol at 3 Tesla which included DWI with b-values of 50, 400,
      800, and 1000 s/mm2. Apparent diffusion coefficient maps were calculated applying
      a standard mono-exponential fit, while a non-Gaussian kurtosis fit was used to
      obtain DKI maps. ADC as well as Kurtosis-corrected diffusion ( D) values were
      quantified by region of interest analysis and compared between lesions. Results
      Sixty-eight hepatic lesions (hepatocellular carcinoma [HCC] [n = 25]; hepatic
      adenoma [n = 4], cysts [n = 18]; hepatic hemangioma [HH] [n = 18]; and focal
      nodular hyperplasia [n = 3]) were identified. Differentiation of malignant and
      benign lesions was possible based on both DWI ADC as well as DKI D-values ( P
      values were in the range of 0.04 to < 0.0001). Conclusion In vivo abdominal DKI
      calculated using standard b-values is feasible and enables quantitative
      differentiation between malignant and benign liver lesions. Assessment of
      conventional ADC values leads to similar results when using b-values below 1000
      s/mm2 for DKI calculation.

PMID- 28454488
TI  - Perception and communication of risk in decision making by persons with dementia.
AB  - Communication of risks must involve people with dementia meaningfully to ensure
      informed and inclusive decision-making processes. This qualitative study explored
      concepts of risk from the perspective of persons with dementia and their
      experiences of communicating risk with family members and professionals. Data was
      analysed using grounded theory. Seventeen people in Northern Ireland with mild
      moderate dementia who had recently made a decision about their daily life or care
      involving consideration of risks were interviewed between November 2015 and
      November 2016. A wide range of actual or feared risks were identified relating
      to: daily activities; hobbies and socialising; mental health and medicines; and
      risks to and from others. 'Risk' often held emotional rather than probability
      connotations. Constructive communications to address issues were presented.
      Problem-solving models of both active and passive decision-making about risks
      were evident. Effective risk communication in informed decision-making processes
      about health and social care is discussed.

PMID- 28454489
TI  - Allergies, antibiotics use, and multiple sclerosis.
AB  - BACKGROUND: The associations between allergies, antibiotics use, and multiple
      sclerosis (MS) remain controversial and their mediating or moderating effects
      have not yet been examined. We aimed to assess the direct and indirect influences
      of allergies and antibiotics use on MS development, and their interactions.
      METHODS: A 1:3 matched case-control study was performed using the National
      Ambulatory Medical Care Survey database from 2006 to 2013 in the USA. Multiple
      sclerosis was identified based on the ICD-9 code (340.0) in any position. Cases
      were matched to their controls based on survey year, age, gender, race, payer
      type, region, and tobacco use. Allergy diseases and antibiotics prescriptions
      were extracted by ICD-9 code and drug classification code, respectively. Both
      generalized structural equation model and MacArthur approach were used to examine
      their intrinsic relationships. RESULTS: The weighted prevalence of MS was 133.7
      per 100,000 visits. A total of 829 MS patients and 2441 controls were matched.
      Both respiratory tract allergies (OR = 0.29, 95% CI: 0.18, 0.49) and other
      allergies (OR = 0.38, 95% CI: 0.19, 0.77) were associated with a reduction of the
      risk of MS. Patients with respiratory tract allergies were more likely to use
      penicillin (OR = 8.73, 95% CI: 4.12, 18.53) and other antibiotics (OR = 3.77, 95%
      CI: 2.72, 5.21), and those with other allergies had a higher likelihood of
      penicillin use (OR = 4.15, 95% CI: 1.27, 13.54); however, the link between
      antibiotics use and MS was not confirmed although penicillin use might mediate
      the relationship between allergies and MS. CONCLUSIONS: The findings supported
      allergy as a protective factor for MS development. We also suggest antibiotics
      use might not be a suitable indicator of bacterial infection to investigate the
      cause of MS.

PMID- 28454490
TI  - CT perfusion in predicting the morbidity and prognosis of hypoxic-ischemic
      encephalopathy after off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: To investigate the perfusion parameters of computed tomography (CT) in
      hypoxicischemic encephalopathy (HIE) after off-pump coronary artery bypass
      grafting (OPCABG), and its potential in predicting the occurrence and prognosis
      of hypoxic-ischemic encephalopathy. METHODS: We selected 830 patients. The
      patients were grouped into: HIE and no HIE. HIE patients were further divided
      into two groups: poor prognosis and better prognosis. RESULTS: (1) Patients with
      HIE, who had a history of stroke and hypertension, showed more severe stenosis on
      CTA and more perfusion abnormalities compared to non-HIE patients (p < 0.05). (2)
      The differences in frontal, temporal, occipital lobe rTTP, and occipital lobe
      rMTT in patients with or without HIE were statistically significant (p < 0.05).
      (3) Logistic regression analysis showed that the difference in occipital lobe
      rTTP was an independent risk factor for the morbidity in HIE. (4) HIE patients,
      if they had a history of an abnormal CT, showed poor prognosis (p < 0.05).
      Furthermore, in these patients, CT images showed significant differences in right
      frontal, occipital, basal ganglia rTTP, as well as left temporal, occipital,
      basal ganglia rTTP, as well as frontal lobe rMTT. (5) Three principal components
      (F1, F2, F3) can be used to generalize all indexes. CONCLUSION: The difference in
      occipital lobe rTTP on CTA perfusion may be a potential predictor of HIE.
      Furthermore, abnormal CT and rTTP may be used for predicting the prognosis in HIE
      patients. Three principal components (F1 as a reflection of CBF, F2 as reflection
      of TTP, F3 as a reflection of MTT) can be used to generally describe perfusion
      parameters.

PMID- 28454491
TI  - Extension of the clomiphene citrate stair-step protocol to gonadotropin treatment
      in women with clomiphene resistant polycystic ovarian syndrome.
AB  - Our objective was to evaluate the safety and efficacy of direct initiation of
      gonadotropin ovarian stimulation without prior withdrawal bleeding in anovulatory
      clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS) patients.
      Eighteen PCOS patients underwent ovulation induction with CC using a stair-step
      regimen. Patients who failed to respond to the maximal dose of CC initiated
      gonadotropin stimulation without inducing withdrawal bleeding, using the chronic
      low dose regimen. The primary outcome measure was the time to ovulation from the
      beginning of CC treatment until the day of ovulatory trigger. This was compared
      with the time to ovulation calculated according to the traditional approach,
      which includes inducing progesterone withdrawal bleeding between each CC dose
      increment and before gonadotropin therapy. The time to ovulation in the study
      group was 67.0 +/- 6.8 days. The estimated time to ovulation according to the
      traditional approach was approximately 110 days. The clinical pregnancy rate was
      44% (8/18), and all pregnancies were singletons. One patient miscarried; hence
      the live birth rate was 38.9% (7/18). Direct initiation of gonadotropin therapy
      without prior induction of withdrawal bleeding in clomiphene resistant PCOS
      patients results in considerable reduction of the time to ovulation and is both
      safe and efficacious.

PMID- 28454493
TI  - Validity in Phallometric Testing for Sexual Interests in Children: A Meta
      Analytic Review.
AB  - Valid assessment of pedohebephilic interests (i.e., sexual interest in children)
      is fundamental to forensic clinical practice. Phallometric testing-which measures
      changes in penile circumference or volume, while stimuli depicting different ages
      and sexual activities are presented-is widely used in clinical and research
      settings to detect such interests. This meta-analysis summarizes studies
      comparing sexual offenders against children and various types of controls on
      phallometric tests for pedohebephilic interests (37 samples; N = 6,785) and
      studies examining the relationship between phallometric test scores and sexual
      reoffending (16 samples; N = 2,709). The findings suggest that several
      phallometric testing procedures are valid indicators of pedohebephilic interest.
      Certain methodological features of phallometric tests were associated with
      greater validity, such as, slide or audio-plus-slide stimuli and z-score-based
      indices. In addition, phallometric tests for pedohebephilic, pedophilic, and
      hebephilic interests predicted sexual reoffending which provides further evidence
      that phallometric test scores are valid indicators of sexual interest in
      children. In general, the interpretation of phallometric test scores as
      indicators of pedohebephilic interests is supported.

PMID- 28454492
TI  - Evaluation of the isoflavones and estrogen effects on the rat adrenal.
AB  - The aim of this study was to evaluate the morphometry and the gene expression of
      Ki-67, VEGF and caspase 3 and the stress oxidative in the adrenal gland of
      ovariectomized rats treated with estrogen or isoflavones. We used 15 Wistar rats
      ovariectomized treated with isoflavones or estrogen during 30 days. At the end of
      the treatment, the left adrenal gland was removed for subsequent histological
      studies and the right was used to evaluate gene expression of angiogenesis (VEGF
      A), cell proliferation (Ki-67), apoptose (caspase 3 clivated) and oxidative
      stress. Treatment with estrogen showed a largest increase in the layers of the
      adrenal cortex than with isoflavones. These hypertrofic effects agree with higher
      expression elevation of Ki67 and VEGF, which did not occur with the caspase 3,
      indicating that isoflavones have great proliferative effect on the adrenal gland.
      Similar results were also observed on superoxide quantification show that
      isoflavone has a protective effect against oxidative stress. Our results indicate
      positively the trophic therapeutic potential of isoflavones has a protective
      effect and can contribute to the development of effective therapies to decrease
      the symptoms of menopause.

PMID- 28454494
TI  - Preparation and testing of cefquinome-loaded poly lactic-co-glycolic acid
      microspheres for lung targeting.
AB  - The aim of this study was to prepare cefquinome-loaded poly lactic-co-glycolic
      acid (PLGA) microspheres and to evaluate their in vitro and in vivo
      characteristics. Microspheres were prepared using a spry drier and were
      characterized in terms of morphology, size, drug-loading coefficient,
      encapsulation ratio and in vitro release. The prepared microspheres were
      spherical with smooth surfaces and uniform size (12.4 +/- 1.2 MUm). The
      encapsulation efficiency and drug loading of cefquinome was 91.6 +/- 2.6 and 18.3
      +/- 1.3%, respectively. In vitro release of cefquinome from the microspheres was
      sustained for 36 h. In vivo studies identified the lung as the target tissue and
      the region of maximum cefquinome release. A partial lung inflammation was
      observed but disappeared spontaneously as the microspheres were removed through
      in vivo decay. The sustained cefquinome release from the microspheres revealed
      its applicability as a drug delivery system that minimized exposure to healthy
      tissues while increasing the accumulation of therapeutic drug at the target site.
      These results indicated that the spray-drying method of loading cefquinome into
      PLGA microspheres is a straightforward method for lung targeting in animals.

PMID- 28454495
TI  - Prediction value of anti-Mullerian hormone (AMH) serum levels and antral follicle
      count (AFC) in hormonal contraceptive (HC) users and non-HC users undergoing IVF
      PGD treatment.
AB  - Use of hormone contraceptives (HC) is very popular in the reproductive age and,
      therefore, evaluation of ovarian reserve would be a useful tool to accurately
      evaluate the reproductive potential in HC users. We conducted a retrospective
      cohort study of 41 HC users compared to 57 non-HC users undergoing IVF
      preimplantation genetic diagnosis (PGD) aiming to evaluate the effect of HC on
      the levels of anti-Mullerian hormone (AMH), small (2-5 mm), large (6-10 mm) and
      total antral follicle count (AFC) and the ability of these markers to predict IVF
      outcome. Significant differences in large AFC (p = 0.04) and ovarian volume (p <
      0.0001) were seen, however, there were no significant differences in small and
      total AFC or in serum AMH and FSH levels. Oocyte number significantly correlated
      with AMH and total AFC in HC users (p < 0.001) while in non-HC users these
      correlations were weaker. In HC users, the significant predictors of achieving <6
      and >18 oocytes were AFC (ROC-AUC; 0.958, p = 0.001 and 0.883, p = 0.001) and AMH
      (ROC-AUC-0.858, p = 0.01 and 0.878, p = 0.001), respectively. The predictive
      values were less significant in non-HC users. These findings are important in
      women treated for PGD, in ovum donors and for assessing the fertility prognosis
      in women using HC and wishing to postpone pregnancy.

PMID- 28454496
TI  - Canakinumab for the treatment of TNF-receptor associated periodic syndrome.
AB  - INTRODUCTION: TNF-receptor-associated periodic syndrome is an autoinflammatory
      disorder caused by mutations in TNF receptor superfamily 1A gene. The molecular
      pathogenesis of TRAPS remains unclear; it is known that a key role is played by
      mutations in TNFRSF1A that induce the hypersecretion of pro-inflammatory
      cytokines as well as IL-1beta, resulting in uncontrolled inflammatory reactions.
      Furthermore, TNFRSF1A gene mutations result in intracellular stress ultimately
      leading to increased production of interleukin-1beta, but the exact mechanism
      referred to in the connection between TNFRSF1A mutation and increased release of
      IL-1beta, is still under study. This explains why IL-1 inhibition treatment can
      be effective in treating TRAPS patients. The purpose of this review is to discuss
      the safety and efficacy of canakinumab, a high-affinity human monoclonal anti IL
      1beta antibody. Areas covered: The data obtained from case reports, case series,
      Phase II study and a phase III randomized, double-blind, placebo controlled trial
      have been analyzed. Efficacy and safety profiles of canakinumab are discussed.
      Expert commentary: Was discussed an overview of treatment options in TRAPS
      patients. The understanding of pathogenesis of TNF-receptor-associated periodic
      syndrome led to realize why TRAPS patients respond to IL-1 inhibition.
      Canakinumab became approved for the treatment in TRAPS patients very recently.

PMID- 28454497
TI  - MicroRNA-34a alleviates steroid-induced avascular necrosis of femoral head by
      targeting Tgif2 through OPG/RANK/RANKL signaling pathway.
AB  - The study aims to investigate the effect of microRNA-34a (miR-34a) targeting
      Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating
      OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and
      model (RNAKL rat models) groups. The model group was further assigned into model
      control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR
      was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions.
      Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT
      PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG,
      RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene
      assay was used to testify the target relationship between miR-34a and Tgif2.
      Compared with the normal control group, the model group showed increased Tgif2,
      RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions.
      Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA
      expressions. Micro-CT showed cystic degeneration of femoral head, with decreased
      bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular
      number in the model control group compared with the normal control group.
      Compared with the model control group, the miR-34a mimics group showed increased
      BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the
      parameters decreased in the miR-34a inhibitors group. Compared with the normal
      control group, the other groups showed increased Tgif2, RANK and RANKL
      expressions but decreased miR-34a and OPG expressions. Compared with the model
      control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG
      expressions increased in the miR-34a mimics group, while the miR-34a inhibitors
      group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a
      target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through
      targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact
      statement miR-34a can alleviate SANFH through targeting Tgif2 and further
      regulating OPG/RANK/RANKL signaling pathway, which can be used as a new
      theoretical basis for SANFH treatment.

PMID- 28454498
TI  - Efficacy of Citalopram on Acute Ischemic Stroke Outcome: A Randomized Clinical
      Trial.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke (IS) is one of the main causes of death
      and disability in the adult population, and recovery from it is a major health
      concern worldwide. The aim of the present study was to evaluate the effectiveness
      of citalopram on 3-mounth outcome of nondepressed acute IS patients. METHODS: In
      a randomized, placebo-controlled clinical trial, 144 patients with acute IS were
      studied for 3 months. In one group, the patients received oral citalopram 20 mg
      (once daily), and in the other group, they received placebo. All patients
      received standard care, including physiotherapy. Patients with depression were
      excluded throughout the study. The primary outcome of the study was set to a 50%
      reduction in the 3-month National Institutes of Health Stroke Scale compared with
      the baseline scores (Clinical Trial Registration URL: http://www.irct.ir ; Unique
      identifier: IRCT201203192150N2). RESULTS: The mean age of patients was 66.4
      years. Of 144 eligible patients, 15 patients died (4 in the citalopram and 11 in
      the placebo group), and 21 patients did not complete the study follow-up period
      (10 in the citalopram and 11 in the placebo group). The primary outcome of the
      study was achieved in 57 patients (79%) in the citalopram and 39 patients (54%)
      in the placebo group ( P < .001), with risk ratio and number needed to treat of 2
      (CI = 1.2-3) and 4 (CI = 2.5-8.6), respectively. No major adverse events were
      found in either group. CONCLUSIONS: Citalopram is a safe and tolerable medication
      in patients with acute IS, which could improve the outcome in these patients.

PMID- 28454499
TI  - Phenotypic variation in anti-Mullerian hormone (AMH) production per follicle in
      women with polycystic ovary syndrome (PCOS) and isolated polycystic ovarian
      morphology (PCOM): an observational cross-sectional study.
AB  - This observational study compares the ratio of serum anti-Mullerian hormone (AMH)
      to the total antral follicle count (AFC) (as a marker of AMH production per
      follicle) in the various phenotypes of women with polycystic ovary syndrome
      (PCOS) and isolated polycystic ovarian morphology (PCOM). Two hundred and sixty
      two women were recruited. Women with PCOS were divided into four phenotypes based
      on the diagnostic inclusion criteria of oligo-anovulation (OA), hyperandrogenism
      (HA) and polycystic ovarian morphology (PCOM). These included Group A (OA + HA +
      PCOM), Group B (OA + HA), Group C (HA + PCOM) and Group D (OA + PCOM). A ratio of
      serum AMH to total AFC was calculated and expressed as the AMH/AFC ratio which
      was compared in the phenotypes of PCOS and isolated PCOM. The median AMH/AFC
      ratios in PCOS-A, PCOS-D, PCOS-C and PCOM were 1.5, 1.6, 1.2 and 1.1,
      respectively. There were significant differences in the groups compared [F(3,
      238) = 6.14, p = 0.000)]. The ratios were significantly higher in the oligo
      anovulatory phenotypes PCOS-A and PCOS-D than the PCOM (p = 0.004 and 0.002,
      respectively). There was no significant difference in the ratio between ovulatory
      phenotype PCOS-C and PCOM (p = 0.59). The role of androgens and LH in per
      follicle AMH production remains limited. The findings support the hypothesis of a
      key role for AMH in the mechanism of anovulation in PCOS.

PMID- 28454500
TI  - Recent progress in the development of small molecule Nrf2 modulators: a patent
      review (2012-2016).
AB  - INTRODUCTION: The NF-E2-related factor-2 (Nrf2) is a critical transcription
      factor that regulates the expression of many phase II and antioxidant genes to
      maintain the homeostasis. It has many biological functions and plays a central
      role in the cellular defensive machinery. The abnormal regulation of Nrf2 is
      closely associated with multiple diseases. Areas covered: This article first
      discusses the molecular regulatory mechanism of Nrf2-antioxidant response element
      (ARE) signaling. Then patents and publications about Nrf2 activators and
      inhibitors from 2012-2016 are reviewed. Several case studies are emphasized to
      introduce the molecular design strategy, especially on Keap1-Nrf2 protein-protein
      interaction (PPI) inhibitor. Expert opinion: Firstly, new chemotypes of Nrf2
      modulators can be designed in a combination of the progress of both covalent
      modifiers and target selective Keap1-Nrf2 interaction inhibitors. The aim is to
      balance the activity and toxicity of Nrf2 modulators. Secondly, considering many
      known Nrf2 activators, such as DMF and SFN, are electrophilic entities with very
      small molecular weight, we need to update the concept of how to recognize a drug
      candidate. Finally, per the mechanism of the Nrf2 modulator, compounds with the
      most active Nrf2 inductivity maybe not the best choice for the design of an ideal
      chemopreventive agent.

PMID- 28454501
TI  - Carry-over of antineoplastic drug contamination in Dutch hospital pharmacies.
AB  - Background To prevent occupational exposure of hospital staff to cytostatics, a
      mandatory national guideline describing a set of safety measures was issued in
      the Netherlands in 2004. The guideline includes, among other directives,
      obligatory annual wipe testing to assess the efficacy of the local cleaning
      protocol. Full implementation of this guideline was executed in all Dutch
      hospital pharmacies over the next couple of years. Objective We aimed to
      investigate the effect of the national guideline on contamination levels, and
      specifically on the phenomenon of carry-over of traces of antineoplastic drugs
      through contact with surfaces, since this is a potential route of exposure.
      Methods From a database including wipe sample results of 9 hospitals over 10
      years, we extracted all sampled locations in the compounding areas as well as in
      adjacent or bypass rooms and locks. We considered only the locations outside
      safety cabinets or isolators, to examine the containment of contamination and to
      address possible routes of how a contamination can migrate through the
      preparation and distribution areas. The dataset consisted of 2647 wipe samples.
      Results In adjacent rooms, 18 out of 275 wipe samples were contaminated (6%).
      Inside the compounding room, the extracted locations away from the safety
      workbench showed a positive percentage for contamination of 13% (39 out of 297).
      When stratifying the data to sample year, it was shown that contaminations
      outside the preparation room were no longer detectable after 2008. Conclusion
      With this study, we show that implementation of a set of guidelines on safety
      measures can prevent spreading of cytostatic traces from the compounding area in
      hospital pharmacies.

PMID- 28454502
TI  - Prediction of cardiovascular risk in cancer patients of South India using WHO/ISH
      risk prediction charts and Framingham score - A prospective study.
AB  - Objective Despite the fact that cancer and heart diseases are interconnected,
      there is lack of information about the prevalence of cardiovascular risk in
      cancer patients in the South Indian population. With this background, the present
      study sought to predict the cardiovascular disease in cancer patients. Methods A
      prospective, cross-sectional study was conducted in the Department of Medical
      Oncology, Sri Ramachandra University and Hospital, India. Patients' demographic
      details, medical information, height, weight, body mass index, blood pressure,
      total cholesterol and HDL-cholesterol were measured. Two risk prediction tools,
      namely World Health Organization/International Society of hypertension (WHO/ISH)
      risk prediction charts and Framingham score were used to assess the prevalence of
      cardiovascular risk over 10 years. Results A total of 70 patients were included
      for the study. Breast and stomach cancer were found to be most among the study
      patients. Cardiovascular disease was assessed using WHO/ISH and Framingham risk
      assessment tool. With respect to WHO/ISH risk, there is a significant difference
      in gender, type of cancer, smoking status and age between the risk groups. Males
      have a high risk compared to females, and smokers have a high risk compared to
      non-smokers. With respect to Framingham score, there is a significant difference
      in gender, smoking status and systolic blood pressure between the risk groups.
      Males have a high risk compared to females, and smokers have a high risk compared
      to non-smokers. A moderate degree of agreement exists between the two risk
      prediction tools. Conclusion The findings of the study revealed that there is a
      low risk of cardiovascular disease in cancer patients.

PMID- 28454503
TI  - Regulatory challenges and considerations for the clinical application of CAR-T
      cell anti-cancer therapy.

PMID- 28454504
TI  - Venous malformation as source of a tarsal tunnel syndrome: treat the source or
      the cause of the complaints? A case report.
AB  - Painful tarsal tunnel syndrome is a compression neuropathy with a variety of
      possible sources. As it presents a challenging differential diagnostic problem,
      it is often under-diagnosed. Among the intrinsic and extrinsic factors, varicose
      veins are the main source in case of a venous etiology. We report a case of a 39
      year old male patient who presented with complaints of paresthesia and excessive
      pain of the right foot, especially the medial side. Further work up by
      ultrasonography, magnetic resonance imaging and electromyography revealed an
      extensive congenital venous malformation of the right lower limb with subsequent
      compression of the tibial nerve in the tarsal tunnel. We did not treat the
      source, but the cause by open tarsal tunnel release. Excellent result with
      immediate full relieve of the patients complaints was achieved.

PMID- 28454505
TI  - Equisetum giganteum influences the ability of Candida albicans in forming
      biofilms over the denture acrylic resin surface.
AB  - CONTEXT: Equisetum giganteum L. (Equisetaceae) is an endemic plant of Central and
      South America used in traditional medicine. Natural drugs have been frequently
      used in the treatment of a myriad of diseases, proving to be an alternative to
      synthetic chemicals, and have been intensively studied in the prevention of
      sicknesses, including oral diseases. OBJECTIVE: This study evaluated the in vitro
      antiadherent activity of E. giganteum extract against Candida albicans biofilms.
      MATERIALS AND METHODS: Crystal violet and colony-forming units assays were used
      to quantify the total biofilm biomass and biofilm living cells on a denture base
      acrylic resin pretreated with hydroethanolic extract of E. giganteum in different
      concentrations (50, 25, 16, 8, and 4 mg/mL), after 24 h of biofilm development.
      RESULTS: Equisetum giganteum affected biofilms by reduction of biomass and living
      cells per area of acrylic specimens. The results revealed reduction of 15-44% of
      the biofilm mass and reduction of numbers of colony-forming units (CFUs) present
      in biofilms (79%) compared to the untreated control (CTRL/PBS). At all
      concentrations, it demonstrated important antiadherent activity on Candida
      albicans biofilms, the main microbe in denture stomatitis. DISCUSSION AND
      CONCLUSION: The present findings show that E. giganteum antimicrobial effects may
      qualify the extract as a promising natural alternative for topical treatment or
      prevention of denture stomatitis. The usage of drugs made of natural products
      shows advantages in relation to synthetic drugs on the market, such as lower
      cost, lower toxicity, and in relation to the occurrence of microbial resistance.

PMID- 28454506
TI  - Antioxidant and anti-inflammatory activities of Aerva pseudotomentosa leaves.
AB  - CONTEXT: Aerva pseudotomentosa Blatt. & Hallb. (Amaranthaceae), commonly called
      "Bui";, is a medicinal plant of the arid region. It is used for the treatment of
      inflammatory disorders, such as rheumatic pain, and healing of wounds, which are
      associated with oxidative stress. OBJECTIVE: The present study evaluated the
      antioxidant potential of Aerva pseudotomentosa leaves by in vitro models and its
      anti-inflammatory effect in rats. MATERIAL AND METHODS: The aqueous extract
      (APAE) was analyzed by HPTLC and HPLC. The antioxidant effect of APAE was
      evaluated by various in vitro methods [DPPH (1, 1-diphenyl-2-picryl-hydrazil) and
      hydrogen peroxide free radical scavenging, reducing power, and anti-lipid
      peroxidation assays]. Anti-inflammatory effect was studied in carrageenan and
      formalin-induced paw oedema models in rats. APAE (200 and 400 mg/kg) and standard
      drug, indomethacin (10 mg/kg), were administered orally 1 h before
      carrageenan/formalin administration and inflammation was noted up to 5 h.
      RESULTS: HPLC analysis of APAE revealed the presence of rutin. APAE showed
      significant scavenging effect on DPPH (IC50 49.37 MU g/mL) and peroxide (IC50
      288.2 MU g/mL) radicals. The extract exhibited reducing potential and inhibition
      of lipid peroxidation. APAE treatment significantly attenuated mean increase in
      paw volume and exhibited inhibition of paw oedema in both in vivo models with
      inhibition of 45.11% and 49.42%, respectively at 5 h. DISCUSSION AND CONCLUSION:
      APAE exhibited <italic>in vitro</italic> antioxidant and anti-inflammatory
      activities. Anti-inflammatory effect of APAE may be attributed to its antioxidant
      potential, due to the presence of rutin and other phenolics. This study
      substantiates folk use of leaves in inflammatory disorders.

PMID- 28454507
TI  - Serum chemerin level during the first trimester of pregnancy and the risk of
      gestational diabetes mellitus.
AB  - OBJECTIVE: To investigate the association between chemerin level in the first
      trimester of pregnancy and the risk of gestational diabetes mellitus. METHODS:
      The blood samples of 212 women at 8-12 weeks of gestation were collected. After
      screening for gestational diabetes mellitus (GDM), 19 women with GDM and 20 women
      randomly selected from 144 women with normal glucose tolerance (NGT) were
      included in the study. Blood samples were collected from these women.
      Triglycerides, glucose, total cholesterol, and HDL cholesterol, LDL cholesterol,
      insulin and chemerin were measured. Gestational weight gain and body mass index
      was assessed. RESULTS: Serum levels of chemerin were significantly elevated
      during late gestation, and the risk of GDM was positively associated with
      maternal serum chemerin in the first trimester. CONCLUSION: Serum chemerin level
      during the first trimester of pregnancy has the potential to predict risk of GDM.

PMID- 28454508
TI  - Endometrial flushing alphaVbeta3 integrin, glycodelin and PGF2alpha levels for
      evaluating endometrial receptivity in women with polycystic ovary syndrome, myoma
      uteri and endometrioma.
AB  - The aim of this cross-sectional study is to compare endometrial flushing fluid
      levels of alphaVbeta3 integrin, glycodelin and PGF2alpha during the midluteal
      phase of the menstrual cycle of women with polycystic ovary syndrome (PCOS, n =
      20), myoma uteri (n = 20) and endometrioma (n = 19) with the healthy controls (n
      = 20). After collecting samples at the midluteal phase of ovulatory volunteers
      and storing them at -80  degrees C, alphaVbeta3 integrin, glycodelin and
      PGF2alpha levels were analyzed using ELISA. The mean ages of the groups were
      28.90 +/- 5.45, 37.25 +/- 2.73, 32.84 +/- 6.62 and 32.15 +/- 5.18 in PCOS, myoma
      uteri, endometrioma and control groups, respectively. The alphaVbeta3 integrin
      level (ng/ml) was statistically significantly higher in endometrioma group (9.70
      +/- 1.72, p < 0.05) as compared to myoma uteri and control groups. Similarly,
      glycodelin level (ng/ml) was significantly higher in endometrioma group (341.04
      +/- 93.32) than PCOS (p < 0.01), myoma uteri (p < 0.001) and healthy subjects (p
      < 0.001). Moreover, PGF2alpha level (350.04 +/- 464.50 ng/ml) was significantly
      higher in PCOS group relative to myoma uteri (p < 0.001), endometrioma (p < 0.05)
      and control (p < 0.05) groups. In conclusion, alphaVbeta3 integrin level was
      significantly higher in endometrioma subjects than those with myoma uteri and
      control groups; glycodelin level was significantly higher in endometrioma group
      than other three groups, and lastly, PCOS patients had significantly higher
      PGF2alpha levels than those patients with myoma uteri, endometrioma and controls.

PMID- 28454509
TI  - Nutrition in peri-operative esophageal cancer management.
AB  - INTRODUCTION: Nutritional status and dietary intake are increasingly recognized
      as essential areas in esophageal cancer management. Nutritional management of
      esophageal cancer is a continuously evolving field and comprises an interesting
      area for scientific research. Areas covered: This review encompasses the current
      literature on nutrition in the pre-operative, peri-operative, and post-operative
      phases of esophageal cancer. Both established interventions and potential novel
      targets for nutritional management are discussed. Expert commentary: To ensure an
      optimal pre-operative status and to reduce peri-operative complications, it is
      key to assess nutritional status in all pre-operative esophageal cancer patients
      and to apply nutritional interventions accordingly. Since esophagectomy results
      in a permanent anatomical change, a special focus on nutritional strategies is
      needed in the post-operative phase, including early initiation of enteral
      feeding, nutritional interventions for post-operative complications, and
      attention to long-term nutritional intake and status. Nutritional aspects of pre
      optimization and peri-operative management should be incorporated in novel
      Enhanced Recovery After Surgery programs for esophageal cancer.

PMID- 28454510
TI  - Home oxygen therapy: evidence versus reality.
AB  - INTRODUCTION: LTOT is a well-established treatment option for hypoxemic patients.
      Scientific evidence for its benefits of LTOT dates back to the 1980s, when two
      randomized controlled trials showed prolonged survival in COPD-patients
      undergoing LTOT for at least 15 hours/day. In contrast, the potential benefits of
      LTOT in non-COPD-patients has not been well researched and the recommendations
      for its application are primarily extrapolated from trials on COPD-patients.
      Recently, a large trial confirmed that COPD-patients who don't meet classic
      indication criteria, and have moderate desaturation at rest or during exercise,
      do not benefit from oxygen therapy. Also the significant technical evolution of
      LTOT devices has improved its application. Areas covered: A literature research
      was performed in pubmed regarding home oxygen therapy (terms: LTOT, ambulatory
      oxygen therapy, short burst oxygen therapy, nocturnal oxygen therapy). Expert
      commentary: LTOT proved a survival benefit for COPD patients about 30 years ago.
      Whether the results of these trials are still valid for patients under modern
      treatment guidelines remains unknown. Nevertheless, the classic indication
      criteria for LTOT still persist in guidelines, since there is a lack of updated
      evidence for the effects of LTOT in more severe hypoxemic patients.

PMID- 28454511
TI  - Percutaneous laser disc decompression versus conventional microdiscectomy for
      patients with sciatica: Two-year results of a randomised controlled trial.
AB  - Background Percutaneous laser disc decompression is a minimally invasive
      treatment, for lumbar disc herniation and might serve as an alternative to
      surgical management of sciatica. In a randomised trial with two-year follow-up we
      assessed the clinical effectiveness of percutaneous laser disc decompression
      compared to conventional surgery. Materials and methods This multicentre
      randomised prospective trial with a non-inferiority design, was carried out
      according to an intent-to-treat protocol with full institutional review board
      approval. One hundred and fifteen eligible surgical candidates, with sciatica
      from a disc herniation smaller than one-third of the spinal canal, were randomly
      allocated to percutaneous laser disc decompression ( n = 55) or conventional
      surgery ( n = 57). The main outcome measures for this trial were the Roland
      Morris Disability Questionnaire for sciatica, visual analogue scores for back and
      leg pain and the patient's report of perceived recovery. Results The primary
      outcome measures showed no significant difference or clinically relevant
      difference between the two groups at two-year follow-up. The re-operation rate
      was 21% in the surgery group, which is relatively high, and with an even higher
      52% in the percutaneous laser disc decompression group. Conclusion At two-year
      follow-up, a strategy of percutaneous laser disc decompression, followed by
      surgery if needed, resulted in non-inferior outcomes compared to a strategy of
      microdiscectomy. Although the rate of reoperation in the percutaneous laser disc
      decompression group was higher than expected, surgery could be avoided in 48% of
      those patients that were originally candidates for surgery. Percutaneous laser
      disc decompression, as a non-surgical method, could have a place in the treatment
      arsenal of sciatica caused by contained herniated discs.

PMID- 28454512
TI  - Optimization of the French cystic fibrosis newborn screening programme by a
      centralized tracking process.
AB  - Objectives To evaluate the French cystic fibrosis newborn screening algorithm,
      based on data tracked by a centralized monitoring process, from 2002 to 2014. The
      programme aimed to attain European Standards in terms of positive predictive
      value, sensitivity, the ratio of screen positive patients diagnosed with cystic
      fibrosis to infants who screen positive but with inconclusive diagnosis (CFSPID),
      and time to diagnosis. Methods Retrospective analysis of programme performance,
      compliance with the algorithm, and changes in screening strategy. Results
      Modifications in the flow chart protocol improved the positive predictive value
      to 0.31 while maintaining the sensitivity at 0.95. Among infants diagnosed with
      cystic fibrosis, or identified as CFSPID, sweat test results were obtained for
      94%, and two mutations were identified after exhaustive screening for the gene,
      when applicable, in 99.6%. The rate of pending diagnosis was very low (0.5%). The
      ratio of infants with cystic fibrosis:CFSPID was 6.3:1. Age at initial visit at
      the CF centre was <= 35 days, respectively, in 53%/26%. Conclusion Performances
      were in agreement with European standards, but timeliness of initial visit needed
      improvement. Our data complement an accumulating body of evidence demonstrating
      that attention must be paid to such ethical considerations as limiting carrier
      detection and inconclusive diagnosis. Newborn screening programmes should have a
      rigorous centralized monitoring process to warrant adjustments for improving
      performance to attain consensus guidelines.

PMID- 28454513
TI  - MYCbase: a database of functional sites and biochemical properties of Myc in both
      normal and cancer cells.
AB  - BACKGROUND: Myc is an essential gene having multiple functions such as in cell
      growth, differentiation, apoptosis, genomic stability, angiogenesis, and disease
      biology. A large number of researchers dedicated to Myc biology are generating a
      substantial amount of data in normal and cancer cells/tissues including Burkitt's
      lymphoma and ovarian cancer. RESULTS: MYCbase (
      http://bicresources.jcbose.ac.in/ssaha4/mycbase ) is a collection of
      experimentally supported functional sites in Myc that can influence the
      biological cellular processes. The functional sites were compiled according to
      their role which includes mutation, methylation pattern, post-translational
      modifications, protein-protein interactions (PPIs), and DNA interactions. In
      addition, biochemical properties of Myc are also compiled, which includes
      metabolism/pathway, protein abundance, and modulators of protein-protein
      interactions. The OMICS data related to Myc- like gene expression, proteomics
      expression using mass-spectrometry and miRNAs targeting Myc were also compiled in
      MYCbase. The mutation and pathway data from the MYCbase were analyzed to look at
      the patterns and distributions across different diseases. There were few
      proteins/genes found common in Myc-protein interactions and Myc-DNA binding, and
      these can play a significant role in transcriptional feedback loops. CONCLUSION:
      In this report, we present a comprehensive integration of relevant information
      regarding Myc in the form of MYCbase. The data compiled in MYCbase provides a
      reliable data resource for functional sites at the residue level and biochemical
      properties of Myc in various cancers.

PMID- 28454514
TI  - QueryOR: a comprehensive web platform for genetic variant analysis and
      prioritization.
AB  - BACKGROUND: Whole genome and exome sequencing are contributing to the
      extraordinary progress in the study of human genetic variants. In this fast
      developing field, appropriate and easily accessible tools are required to
      facilitate data analysis. RESULTS: Here we describe QueryOR, a web platform
      suitable for searching among known candidate genes as well as for finding novel
      gene-disease associations. QueryOR combines several innovative features that make
      it comprehensive, flexible and easy to use. Instead of being designed on specific
      datasets, it works on a general XML schema specifying formats and criteria of
      each data source. Thanks to this flexibility, new criteria can be easily added
      for future expansion. Currently, up to 70 user-selectable criteria are available,
      including a wide range of gene and variant features. Moreover, rather than
      progressively discarding variants taking one criterion at a time, the
      prioritization is achieved by a global positive selection process that considers
      all transcript isoforms, thus producing reliable results. QueryOR is easy to use
      and its intuitive interface allows to handle different kinds of inheritance as
      well as features related to sharing variants in different patients. QueryOR is
      suitable for investigating single patients, families or cohorts. CONCLUSIONS:
      QueryOR is a comprehensive and flexible web platform eligible for an easy user
      driven variant prioritization. It is freely available for academic institutions
      at http://queryor.cribi.unipd.it/ .

PMID- 28454515
TI  - Identification and profiling of Cyprinus carpio microRNAs during ovary
      differentiation by deep sequencing.
AB  - BACKGROUND: MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate
      gene expression by targeting specific mRNAs. However, the possible role of miRNAs
      in the ovary differentiation and development of fish is not well understood. In
      this study, we examined the expression profiles and differential expression of
      miRNAs during three key stages of ovarian development and different developmental
      stages in common carp Cyprinus carpio. RESULTS: A total of 8765 miRNAs were
      identified, including 2155 conserved miRNAs highly conserved among various
      species, 145 miRNAs registered in miRBase for common carp, and 6505 novel miRNAs
      identified in common carp for the first time. Comparison of miRNA expression
      profiles among the five libraries identified 714 co-expressed and 2382 specific
      expressed miRNAs. Overall, 150, 628, and 431 specifically expressed miRNAs were
      identified in primordial gonad, juvenile ovary, and adult ovary, respectively.
      MiR-6758-3p, miR-3050-5p, and miR-2985-3p were highly expressed in primordial
      gonad, miR-3544-5p, miR-6877-3p, and miR-9086-5p were highly expressed in
      juvenile ovary, and miR-154-3p, miR-5307-5p, and miR-3958-3p were highly
      expressed in adult ovary. Predicted target genes of specific miRNAs in primordial
      gonad were involved in many reproductive biology signaling pathways, including
      transforming growth factor-beta, Wnt, oocyte meiosis, mitogen-activated protein
      kinase, Notch, p53, and gonadotropin-releasing hormone pathways. Target-gene
      prediction revealed upward trends in miRNAs targeting male-bias genes, including
      dmrt1, atm, gsdf, and sox9, and downward trends in miRNAs targeting female-bias
      genes including foxl2, smad3, and smad4. Other sex-related genes such as sf1 were
      also predicted to be miRNA target genes. CONCLUSIONS: This comprehensive miRNA
      transcriptome analysis demonstrated differential expression profiles of miRNAs
      during ovary development in common carp. These results could facilitate future
      exploitation of the sex-regulatory roles and mechanisms of miRNAs, especially in
      primordial gonads, while the specifically expressed miRNAs represent candidates
      for studying the mechanisms of ovary determination in Yellow River carp.

PMID- 28454517
TI  - Findings from a prospective cohort study evaluating the effects of International
      Health Advisors' work on recently settled migrants' health.
AB  - BACKGROUND: Several interventions have been carried out to tackle health
      inequalities between migrant groups, especially refugees, and native-born
      European populations. These initiatives are often address language or cultural
      barriers. One of them is the International Health Advisors (IHA) in Sweden; a
      peer education intervention aimed at providing health information for recently
      settled migrants. It is known that social determinants, such as educational level
      and access to social capital, affect health. Social determinants may also affect
      how health information is received and transformed into practice. The aims of
      this study was to a) assess the impact of the IHA on recently settled migrants'
      self-reported health status, and received health information; b) determine the
      moderating role of educational level and social capital; and c) critically
      discuss the outcomes and suggest implications for health promotion practice.
      METHODS: The study was designed as a prospective cohort study. A postal
      questionnaire translated to Arabic was sent to recently settled Iraqi migrants in
      eight counties in Sweden, in May 2008 and May 2010. Two of the counties were
      exposed to the intervention, and six were used as references. RESULTS: The
      proportion of individuals who reported that they had received information on
      healthy diet and physical exercise was higher in the intervention group than in
      the non-intervention group (OR 2.31, 95% CI 1.02-5.22), after adjustments. Low
      social participation was negatively associated with deteriorated or unchanged
      health needs (OR 0.47, 95% CI 0.24-0.92). No other statistically significant
      differences in health outcomes could be observed between the groups. No signs of
      effect modification on this association by social capital or educational level
      could be found. CONCLUSIONS: Health information provided by the IHA increased
      self-reported level of knowledge on healthy diet and physical exercise. The
      interpretation of the observed negative association between low social
      participation and deteriorated or unchanged health needs is that participation
      was limited to one's own social group, and therefore had limited positive
      influence on health seeking behaviour. The lack of measurable improvements in
      health status could be explained by limitations in the study, in the theoretical
      assumptions underlying the intervention, and in the implementation of the
      intervention. Further research is needed to understand success factors in health
      promoting interventions among recently settled migrants better.

PMID- 28454516
TI  - Early childhood obesity: a survey of knowledge and practices of physicians from
      the Middle East and North Africa.
AB  - BACKGROUND: Childhood obesity is one of the most serious public health issues of
      the twenty-first century affecting even low- and middle-income countries.
      Overweight and obese children are more likely to stay obese into adulthood. Due
      to the paucity of data on local practices, our study aimed to assess the
      knowledge and practices of physicians from the Middle East and North Africa
      region with respect to early-onset obesity. METHODS: A specific questionnaire
      investigating the perception and knowledge on early-onset obesity was circulated
      to healthcare providers (general physicians, pediatricians, pediatric
      gastroenterologist, neonatologists) practicing in 17 Middle East and North
      African countries. RESULTS: A total of 999/1051 completed forms (95% response)
      were evaluated. Of all respondents, 28.9% did not consistently use growth charts
      to monitor growth during every visit and only 25.2% and 46.6% of respondents were
      aware of the correct cut-off criterion for overweight and obesity, respectively.
      Of those surveyed, 22.3, 14.0, 36.1, 48.2, and 49.1% of respondents did not
      consider hypertension, type 2 diabetes, coronary heart disease, fatty liver
      disease, and decreased life span, respectively, to be a long-term complication of
      early childhood obesity. Furthermore, only 0.7% of respondents correctly answered
      all survey questions pertaining to knowledge of early childhood overweight and
      obesity. CONCLUSION: The survey highlights the low use of growth charts in the
      evaluation of early childhood growth in Middle East and North Africa region, and
      demonstrated poor knowledge of healthcare providers on the short- and long-term
      complications of early-onset obesity. This suggests a need for both continued
      professional education and development, and implementation of guidelines for the
      prevention and management of early childhood overweight and obesity.

PMID- 28454519
TI  - Factors affecting the accuracy of genomic selection for growth and wood quality
      traits in an advanced-breeding population of black spruce (Picea mariana).
AB  - BACKGROUND: Genomic selection (GS) uses information from genomic signatures
      consisting of thousands of genetic markers to predict complex traits. As such, GS
      represents a promising approach to accelerate tree breeding, which is especially
      relevant for the genetic improvement of boreal conifers characterized by long
      breeding cycles. In the present study, we tested GS in an advanced-breeding
      population of the boreal black spruce (Picea mariana [Mill.] BSP) for growth and
      wood quality traits, and concurrently examined factors affecting GS model
      accuracy. RESULTS: The study relied on 734 25-year-old trees belonging to 34 full
      sib families derived from 27 parents and that were established on two contrasting
      sites. Genomic profiles were obtained from 4993 Single Nucleotide Polymorphisms
      (SNPs) representative of as many gene loci distributed among the 12 linkage
      groups common to spruce. GS models were obtained for four growth and wood traits.
      Validation using independent sets of trees showed that GS model accuracy was
      high, related to trait heritability and equivalent to that of conventional
      pedigree-based models. In forward selection, gains per unit of time were three
      times higher with the GS approach than with conventional selection. In addition,
      models were also accurate across sites, indicating little genotype-by-environment
      interaction in the area investigated. Using information from half-sibs instead of
      full-sibs led to a significant reduction in model accuracy, indicating that the
      inclusion of relatedness in the model contributed to its higher accuracies. About
      500 to 1000 markers were sufficient to obtain GS model accuracy almost equivalent
      to that obtained with all markers, whether they were well spread across the
      genome or from a single linkage group, further confirming the implication of
      relatedness and potential long-range linkage disequilibrium (LD) in the high
      accuracy estimates obtained. Only slightly higher model accuracy was obtained
      when using marker subsets that were identified to carry large effects, indicating
      a minor role for short-range LD in this population. CONCLUSIONS: This study
      supports the integration of GS models in advanced-generation tree breeding
      programs, given that high genomic prediction accuracy was obtained with a
      relatively small number of markers due to high relatedness and family structure
      in the population. In boreal spruce breeding programs and similar ones with long
      breeding cycles, much larger gain per unit of time can be obtained from genomic
      selection at an early age than by the conventional approach. GS thus appears
      highly profitable, especially in the context of forward selection in species
      which are amenable to mass vegetative propagation of selected stock, such as
      spruces.

PMID- 28454518
TI  - Transcriptome-wide N 6 -methyladenosine methylome profiling of porcine muscle and
      adipose tissues reveals a potential mechanism for transcriptional regulation and
      differential methylation pattern.
AB  - BACKGROUND: N 6 -methyladenosine (m6A) is the most prevalent internal form of
      modification in messenger RNA in higher eukaryotes and potential regulatory
      functions of reversible m6A methylation on mRNA have been revealed by mapping of
      m6A methylomes in several species. m6A modification in active gene regulation
      manifests itself as altered methylation profiles in a tissue-specific manner or
      in response to changing cellular or species living environment. However, up to
      date, there has no data on m6A porcine transcriptome-wide map and its potential
      biological roles in adipose deposition and muscle growth. METHODS: In this work,
      we used methylated RNA immunoprecipitation with next-generation sequencing (MeRIP
      Seq) technique to acquire the first ever m6A porcine transcriptome-wide map.
      Transcriptomes of muscle and adipose tissues from three different pig breeds, the
      wild boar, Landrace, and Rongchang pig, were used to generate these maps.
      RESULTS: Our findings show that there were 5,872 and 2,826 m6A peaks
      respectively, in the porcine muscle and adipose tissue transcriptomes. Stop
      codons, 3'-untranslated regions, and coding regions were found to be mainly
      enriched for m6A peaks. Gene ontology analysis revealed that common m6A peaks in
      nuclear genes are associated with transcriptional factors, suggestive of a
      relationship between m6A mRNA methylation and nuclear genome transcription. Some
      genes showed tissue- and breed-differential methylation, and have novel
      biological functions. We also found a relationship between the m6A methylation
      extent and the transcript level, suggesting a regulatory role for m6A in gene
      expression. CONCLUSION: This comprehensive map provides a solid basis for the
      determination of potential functional roles for RNA m6A modification in adipose
      deposition and muscle growth.

PMID- 28454520
TI  - Physical inactivity and self-reported depression among middle- and older-aged
      population in South Asia: World health survey.
AB  - BACKGROUND: With the increase in the understanding of the influence of various
      lifestyle factors such as sedentary behaviour and level of physical activity (PA)
      on physical and mental health, there has been a growing research interest on how
      physical inactivity correlates with depressive outcomes across countries. The
      present study aimed to examine 1) the pattern of engaging in PA among middle- and
      older-aged population in four South Asian countries, and 2) whether PA is
      associated with higher prevalence of depression. METHODS: This cross-sectional
      study is based on country-representative data obtained from WHO's World Health
      Survey (WHS). Subjects were 7204 men and women aged above 50 years from
      Bangladesh, India, Nepal and Sri Lanka, all of which are classified as Low-and
      middle-income countries (LMICs) in World Bank reports. Outcome variables were
      self-ported depression (SRD) and ever being diagnosed with depression.
      Association between frequency of moderate (MPA) and vigorous physical activity
      (VPA) and depression was analysed by multivariable regression methods. RESULT:
      Prevalence of self-reported depression was respectively 47.7%, 40.3%, 40.4% and
      11.4% in Bangladesh, India, Nepal and Sri Lanka. Prevalence of being ever
      diagnosed with depression was highest in Nepal (38.7%), followed by India
      (17.7%), Bangladesh (2.5%) and Sri Lanka (2%). Multivariable analysis shown
      statistically significant association between PA and diagnosed depression in
      Bangladesh and India, but not with SRD. In Bangladesh, compared to those who
      reported engaging in MPA on daily basis, the odds of reporting diagnosed
      depression were more than five times higher [AOR = 5.512; 95% CI = 1.159-26.21]
      for those who never took MPA. In India, those never took VPA had 44% higher [AOR
      = 1.442; 95% CI = 1.046-1.987] odds of being diagnosed with depression compared
      those who never engaged in VPA. CONCLUSION: Lower frequency of vigorous physical
      activity were significantly associated with higher rates of depression diagnosed.
      Based on the findings, it is recommendable that health programs targeting mental
      health among middle- and older-aged population take steps to promote the level of
      PA within a multi-dimensional depression prevention framework. Longitudinal
      studies are needed to understand the role of vigorous and moderate physical
      activity on the onset and intervention of depression among elderly population in
      the region.

PMID- 28454521
TI  - Age and gender differences in the association between social participation and
      instrumental activities of daily living among community-dwelling elderly.
AB  - BACKGROUND: Although many studies have suggested social participation (SP) has
      beneficial effects on elderly people's health, most of them failed to deal with
      paid work. Additionally, few studies have focused on the age effect between SP
      and older people's health. To investigate whether the association between SP,
      including paid work, and instrumental activities of daily living (IADL), exhibits
      not only in gender, but also in age among community-dwelling older adults.
      METHODS: In 2014, we distributed self-administered questionnaires to all
      community-dwelling elderly aged >=65 in two medium-sized cities in Nara
      Prefecture, Japan (n = 32,825). 22,845 residents submitted the questionnaire
      (response rate, 69.6%). Analyzed subjects were limited to 17,680 persons who had
      neither dependency in basic ADL nor missing data for required items. SP was
      assessed based on participation frequency in seven types of social activities:
      volunteer groups, sports groups, hobby groups, cultural groups, senior citizens'
      clubs, neighborhood community associations, and paid work. Using Poisson
      regression models, prevalence ratio for poor IADL was calculated. To examine age
      and gender differences in the association between SP and IADL, we performed
      stratified analyses by age and gender group; male young-old (aged 65-74), male
      old-old (aged >=75), female young-old, and female old-old. RESULTS: Prevalence of
      those with poor IADL was 17.1% in males and 4.5% in females, showing a
      significant gender difference. After adjustment for relevant covariates,
      volunteer groups were inversely associated with poor IADL only in males and the
      relationship was stronger in the old-old group than in the young-old group.
      Conversely, only females had a significant inverse association between paid work
      and poor IADL, and the association was not reliant on their ages but only those
      who participated infrequently had a favorable effect. Influence of age in the
      beneficial association between SP and IADL was generally larger in the old-old
      group than in the young-old group, but hobby groups were inversely associated
      with poor IADL, regardless of age, gender, and frequency. CONCLUSIONS: Our
      results suggest that SP in older age is positively associated with IADL, however,
      the association seems to differ depending on the type of activities participated
      in, the participants' gender, and their age.

PMID- 28454522
TI  - From the neurobiological basis of comorbid alcohol dependence and depression to
      psychological treatment strategies: study protocol of a randomized controlled
      trial.
AB  - BACKGROUND: Alcohol use disorder and depression occur commonly in the community.
      Even though this high-prevalence comorbidity is associated with poorer
      posttreatment outcomes and greater utilization of costly treatment services,
      existing treatment trials often exclude patients with comorbid depressive and
      alcohol use disorders. Past research suggests that symptoms such as craving and
      anhedonia might be associated with alterations within the reward circuit, while
      emotion regulation deficits are related to disruptions within the default mode
      network. The aim of this clinical neuroimaging study is to transfer previous
      research about the reward circuit and default mode network underlying alcohol use
      disorder and depression to achieve a better understanding of neural signatures
      characterizing their comorbidity. In addition, the neurobiological results will
      be used to test whether two psychotherapeutic intervention programs, mindfulness
      based training and behavioral activation training, are able to positively
      influence the identified pathomechanisms. METHODS: By means of functional
      magnetic resonance imaging (fMRI), 60 comorbid alcohol dependent and depressed
      patients are compared to 30 patients with depression only, 30 patients with
      alcohol use disorder only and 30 healthy control participants. Comorbid patients
      are randomized to either receive a behavioral activation or mindfulness based
      training and asked to participate in a second fMRI session and 3 month follow-up
      assessment. Thereby, we plan to explore whether these brief group
      psychotherapeutic intervention programs are able to positively influence the
      identified neurobiological pathomechanisms. The primary outcomes are reward and
      default mode network activity and connectivity evoked by paradigms measuring
      different facets of reward and emotion processing. Secondary outcome measures
      include craving and depression scores, as well as relapse rates. Predictors
      include participants' characteristics, personality traits and indicators of
      mental health. DISCUSSION: The objective of the project is to identify common
      and/or distinct neural signatures underlying the comorbidity of alcohol
      dependence and depression. If the neurobiological understanding of alcohol
      addiction and depression is improved, this could potentially serve as a key
      predictor of treatment response to specific types of behavioral or mindfulness
      therapies hypothesized to alter reward and resting state systems. TRIAL
      REGISTRATION: German Clinical Trial Register DRKS00010249 . The trial was
      registered January 23th 2017.

PMID- 28454523
TI  - Evaluation of a community-based hypertension improvement program (ComHIP) in
      Ghana: data from a baseline survey.
AB  - BACKGROUND: Ghana faces an increasing burden of non-communicable disease with
      rates of hypertension estimated as high as 36% in adults. Despite these high
      rates, hypertension control remains very poor in Ghana (4%). The current project
      aims to implement and evaluate a community-based programme to raise awareness,
      and to improve treatment and control of hypertension in the Eastern Region of
      Ghana. In this paper, we present the findings of the baseline cross-sectional
      survey focusing on hypertension prevalence, awareness, treatment, and control.
      METHODS: To evaluate the ComHIP project, a quasi-experimental design consisted of
      a before and after evaluations are being implemented in the intervention and
      comparison districts. A cohort study component is being implemented in the
      intervention district to assess hypertension control. Background anthropometric
      and clinical data collected as part of the baseline survey were analyzed in STATA
      Version 11. We examined the characteristics of individuals, associated with the
      baseline study outcomes using logistic regression models. RESULTS: We interviewed
      2400 respondents (1200 each from the comparison and intervention districts),
      although final sample sizes after data cleaning were 1170 participants in the
      comparison district and 1167 in the intervention district. With the exception of
      ethnicity, the control and intervention districts compare favorably. Overall
      32.4% of the study respondents were hypertensive (31.4% in the control site; and
      33.4% in the intervention site); 46.2% of hypertensive individuals were aware of
      a previous diagnosis of hypertension (44.7% in the control site, and 47.7% in the
      intervention site), and only around 9% of these were being treated in either arm.
      Hypertension control was 1.3% overall (0.5% in the comparison site, and 2.1% in
      the intervention site). Age was a predictor of having hypertension, and so was
      increasing body mass index (BMI), waist, and hip circumferences. After adjusting
      for age, the risk factors with the greatest association with hypertension were
      being overweight (aOR = 2.30; 95% CI 1.53-3.46) or obese (aOR = 3.61; 95% CI 2.37
      5.51). Older individuals were more likely to be aware of their hypertension
      status than younger people. After adjusting for age people with a family history
      of hypertension or CVD, or having an unhealthy waist hip ratio, were more likely
      to be aware of their hypertension status. CONCLUSIONS: The high burden of
      hypertension among the studied population, coupled with high awareness, yet very
      low level of hypertension treatment and control requires in-depth investigation
      of the bottlenecks to treatment and control. The low hypertension treatment and
      control rates despite current and previous general educational programs
      particularly in the intervention district, may suggest that such programs are not
      necessarily impactful on the health of the population.

PMID- 28454524
TI  - Cost-effectiveness of ceftolozane/tazobactam compared with
      piperacillin/tazobactam as empiric therapy based on the in-vitro surveillance of
      bacterial isolates in the United States for the treatment of complicated urinary
      tract infections.
AB  - BACKGROUND: A challenge in the empiric treatment of complicated urinary tract
      infection (cUTI) is identifying the initial appropriate antibiotic therapy
      (IAAT), which is associated with reduced length of stay and mortality compared
      with initial inappropriate antibiotic therapy (IIAT). We evaluated the cost
      effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam
      (one of the standard of care antibiotics), for the treatment of hospitalized
      patients with cUTI. METHODS: A decision-analytic Monte Carlo simulation model was
      developed to compare the costs and effectiveness of empiric treatment with either
      ceftolozane/tazobactam or piperacillin/tazobactam in hospitalized adult patients
      with cUTI infected with Gram-negative pathogens in the US. The model applies the
      baseline prevalence of resistance as reported by national in-vitro surveillance
      data. RESULTS: In a cohort of 1000 patients, treatment with
      ceftolozane/tazobactam resulted in higher total costs compared with
      piperacillin/tazobactam ($36,413 /patient vs. $36,028/patient, respectively),
      greater quality-adjusted life years (QALYs) (9.19/patient vs. 9.13/patient,
      respectively) and an incremental cost-effectiveness ratio (ICER) of $6128/QALY.
      Ceftolozane/tazobactam remained cost-effective at a willingness to pay of
      $100,000 per QALY compared to piperacillin/tazobactam over a range of input
      parameter values during one-way and probabilistic sensitivity analysis.
      CONCLUSIONS: Model results show that ceftolozane/tazobactam is likely to be cost
      effective compared with piperacillin/tazobactam for the empiric treatment of
      hospitalized cUTI patients in the United States.

PMID- 28454525
TI  - Influence of presence/absence of thyroid gland on the cutoff value for
      thyroglobulin in lymph-node aspiration to detect metastatic papillary thyroid
      carcinoma.
AB  - BACKGROUND: Thyroglobulin measurement with fine-needle aspiration (Tg-FNA) is a
      sensitive method for detecting metastatic papillary thyroid carcinoma (PTC).
      However, the diagnostic threshold is not well established and the influence of
      the thyroid gland on the cutoff value is also controversial. In this study,
      patients were classified into two groups according to the presence or absence of
      thyroid tissue, to determine an appropriate cutoff value for clinical practice.
      METHODS: Patients with a history of thyroid nodules or surgery for PTC and with
      enlarged cervical lymph nodes on an FNA examination were enrolled for Tg-FNA
      detection. RESULTS: One hundred ninety-six lymph nodes (189 patients) were
      included: 100 from preoperative patients, 49 from patients treated with partial
      thyroid ablation, and 47 from patients with total thyroid ablation. In 149 lymph
      nodes from patient with thyroids, the cutoff value for Tg-FNA was 55.99 ng/mL
      (sensitivity, 95.1%; specificity, 100%), whereas in 47 lymph nodes from patients
      without a thyroid, it was 9.71 ng/mL (sensitivity, 96.7%; specificity, 100%).
      Thus, the cutoff value for Tg-FNA was higher in patients with thyroids than in
      patients without thyroids. CONCLUSIONS: The cutoff value for Tg-FNA is influenced
      by residual thyroid tissue, and a higher cutoff value is recommended for patients
      with thyroids than for patients without thyroids.

PMID- 28454526
TI  - Efficacy and tolerability of preservative-free 0.0015% tafluprost in glaucoma
      patients: a prospective crossover study.
AB  - BACKGROUND: The aim of this work is to evaluate efficacy and tolerability of
      preservative containing 0.0015% tafluprost and preservative-free 0.0015%
      tafluprost using a prospective crossover study. METHODS: Primary open angle
      glaucoma (POAG) and normotensive glaucoma (NTG) patients were randomized
      enrolled. Group 1 ("NPT to PT") patients used preservative-free 0.0015%
      tafluprost (NPT) for 6 months and then changed to preservative containing 0.0015%
      tafluprost(PT) for 6 months. Group 2 ("PT to NPT") patients used preservative
      containing 0.0015% tafluprost for 6 months and changed to preservative-free
      0.0015% tafluprost for 6 months. At 1, 3, 6, 7, 9, and 12 months, we measured
      intraocular pressure for efficacy and graded corneal erosion, tear break-up time
      (TBUT), and subjective discomfort. RESULTS: A total of 20 patients and 20 eyes
      were enrolled. In Group 1 and 2, intraocular pressure was well controlled to
      approximately 14 mmHg (9.38-18.46% decrease). Generally, subjective satisfaction
      was improved after changing from PT to NPT (p = 0.03) and TBUT using PT was
      numerically inferior to that using NPT (p = 0.06) but not when changing from NPT
      to PT. CONCLUSION: Both preservative containing and preservative-free 0.0015%
      tafluprost reduced intraocular pressure significantly. In addition, changing
      medication from PT to NPT might improve subjective satisfaction and tear break up
      time. TRIAL REGISTRATION: The trial registration number is NCT 03104621
      (Apr/1/2017). Retrospectively registered.

PMID- 28454527
TI  - Effect of ivabradine on cardiovascular outcomes in patients with stable angina:
      meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Although there are established drugs for treatment of cardiovascular
      diseases, due to adverse effects these drugs may not be clinically applicable to
      all patients. Recent trends have seen the emergence of drugs which act on funny
      current channels to induce selective heart rate reduction. Ivabradine is one such
      drug developed for coronary artery disease and heart failure. There is
      inconsistent evidence about the effect of this selective inhibitor in reduction
      of cardiovascular related mortality and morbidity. Such an inconsistency warrants
      the need for a meta-analysis to consider the effectiveness and efficacy of
      Ivabradine in the treatment of coronary artery disease and heart failure.
      METHODS: Randomized controlled trials with a minimum follow-up period of one year
      were searched in Pub Med/Medline, Embase, Cochrane Central Register of Controlled
      Trials published between 1980 and 2016.Each eligible study was assessed for risk
      of bias by using the Cochrane Risk of Bias Assessment tool. The outcomes assessed
      in this study included: all cause mortality, cardiovascular-related mortality,
      hospitalization for new or worsening heart failure, and adverse events. Subgroup
      analysis and publication bias were assessed. We used Mantel-Haenszel method for
      random-effects. Analysis was done using RevMan5.1TM.This study was registered in
      PROSPERO as [PROSPERO 2016:CRD42016035597]. RESULT: Three trials with a total of
      36,577 participants met the meta-analysis criteria. Pooled analysis showed that
      ivabradine is not effective in reducing cardiovascular deaths (OR: 1.02; CI:0.91
      1.15,P = 0.74), all-cause mortality (OR:1.00; CI:0.91-1.10,P = 0.98), coronary
      revascularization (OR: 0.93, CI: 0.77-1.11, P = 0.41) and hospital admission for
      worsening of heart failure (OR: 0.94, CI: 0.71-1.25, P = 0.69). However, the drug
      was found to significantly increase adverse events: phosphenes (OR:7.77, CI: 4.4
      14.6,P < 0.00001), blurred vision (OR:3.07,CI:2.18-4.32,P < 0.00001), symptomatic
      bradycardia (OR: 6.23, CI: 4.2-9.26, P < 0.00001), and atrial fibrillation (OR:
      1.35, CI: 1.19-1.53, P < 0.0001). Subgroup analysis by duration of follow up on
      cardiovascular outcomes found that there is no difference in effect of ivabradine
      depending on the duration of follow up. There was no publication bias in
      reporting of included studies. CONCLUSION: This meta-analysis suggests that
      ivabradine is not effective in reducing cardiovascular-related morbidity and
      mortality unless used for specific conditions. On the contrary, the use of this
      drug was strongly associated with the onset of untoward and new adverse events.
      This finding strongly supports previous findings and further informs the rational
      and evidence-informed clinical use of ivabradine.

PMID- 28454528
TI  - Asthma control using fluticasone propionate/salmeterol in Asian and non-Asian
      populations: a post hoc analysis of the GOAL study.
AB  - BACKGROUND: To analyse the efficacy of fluticasone propionate (FP) alone and
      combined with salmeterol (SAL) in achieving guideline-defined asthma control in
      Asian patients. METHODS: A post hoc analysis of the GOAL study in which patients
      were stratified by prior-medication use into inhaled corticosteroid (ICS)-naive
      (Stratum [S] 1), low-dose ICS (S2), and medium-dose ICS (S3), and randomised to
      receive FP/SAL or FP. Doses were stepped-up every 12 weeks until Totally
      Controlled asthma or maximum dose was reached (PhI) and then maintained until
      study end (PhII). The primary endpoint was the proportion of patients achieving
      Well-Controlled asthma during PhI. Additional endpoints included Total Control
      and adverse events. Asian and non-Asian patients were analysed separately.
      RESULTS: In Asian patients in PhI, 74% (n = 87/118) in S1 achieved Well
      Controlled asthma with FP/SAL versus 74% (n = 89/121) with FP alone (p = 0.839);
      corresponding values were 76% (n = 81/107) versus 60% (n = 62/104; p = 0.005) in
      S2, and 58% (n = 59/102) versus 43% (n = 41/95; p = 0.015) in S3. More patients
      in all three strata achieved Totally Controlled asthma with FP/SAL versus FP
      alone. Control was achieved more rapidly and with lower ICS doses with FP/SAL
      versus FP. A high proportion of patients who achieved control during PhI
      maintained control during PhII. Similar trends were found in non-Asian patients.
      No new safety concerns were identified. CONCLUSIONS: A greater proportion of
      Asian patients (S2 and S3, for Well-Controlled; all strata, for Totally
      Controlled) achieved guideline-defined asthma control with FP/SAL versus FP
      alone. High proportions of Asian patients in S1 achieved Well-Controlled asthma
      in both treatment groups.

PMID- 28454529
TI  - Association of vertebral compression fractures with physical performance measures
      among community-dwelling Japanese women aged 40 years and older.
AB  - BACKGROUND: Numerous reported studies have shown that vertebral compression
      fractures are associated with impaired function or disability; however, few
      examined their association with objective measures of physical performance or
      functioning. METHODS: We examined the association of vertebral compression
      fractures with physical performance measures in 556 Japanese women aged 40-89
      years. Lateral spine radiographs were obtained and radiographic vertebral
      compression fractures were assessed by quantitative morphometry, defined as
      vertebral heights more than 3 SD below the normal mean. Measures of physical
      performance included walking speed, chair stand time and functional reach.
      Adjusted means of performance-based measures according to the number and severity
      of vertebral compression fractures were calculated using general linear modeling
      methods. RESULTS: After adjusting for age, body mass index, back pain, number of
      painful joints, number of comorbidities and regular physical activities, the
      walking speed of women with two or more compression fractures (1.17 m/s) was
      significantly slower than that of women without compression fracture (1.24 m/s)
      (p = 0.03). Compared with women without compression fracture, chair stand time
      was longer in women with two or more compression fractures (p = 0.01), and
      functional reach was shorter (p = 0.01). No significant differences were observed
      in walking speed, chair stand time, or functional reach between women with one
      compression fracture and those without compression fracture. CONCLUSIONS: Having
      multiple vertebral compression fractures affects physical performance in
      community-dwelling Japanese women. Poor physical functioning may lead to
      functional dependence, accelerated bone loss, and increased risk for falls,
      injuries, and fractures. Preventing vertebral compression fracture is considered
      important for preserving the independence of older adults.

PMID- 28454530
TI  - Dyslipidemia and reference values for fasting plasma lipid concentrations in
      Danish/North-European White children and adolescents.
AB  - BACKGROUND: Dyslipidemia is reported in 27 - 43% of children and adolescents with
      overweight/obesity and tracks into adulthood, increasing the risk of
      cardiovascular morbidity. Cut-off values for fasting plasma lipid concentrations
      are typically set at fixed levels throughout childhood. The objective of this
      cross-sectional study was to generate fasting plasma lipid references for a
      Danish/North-European White population-based cohort of children and adolescents,
      and investigate the prevalence of dyslipidemia in this cohort as well as in a
      cohort with overweight/obesity. METHODS: A population-based cohort of 2141 (1275
      girls) children and adolescents aged 6 - 19 (median 11.5) years was recruited
      from 11 municipalities in Denmark. Additionally, a cohort of children and
      adolescents of 1421 (774 girls) with overweight/obesity aged 6 - 19 years (median
      11.8) was recruited for the study. Height, weight, and fasting plasma lipid
      concentrations were measured on all participants. Smoothed reference curves and
      percentiles were generated using the Generalized Additive Models for Location
      Scale and Shape package in the statistical software R. RESULTS: In the population
      based cohort, plasma concentrations of total cholesterol (TC) (P < 0.05), low
      density lipoprotein cholesterol (LDL) (P < 0.005), and high-density lipoprotein
      cholesterol (HDL) (P < 0.005) were higher in the youngest compared to the oldest
      tertile. Fasting plasma levels of triglycerides (TG) (P < 0.005) increased with
      age in both sexes. In boys, non-HDL was lower in the oldest compared to the
      youngest tertile (P < 0.0005). Concentrations of TC, LDL, non-HDL, and TG were
      higher (P < 0.05), and HDL lower (P < 0.05) in the cohort with overweight/obesity
      in both sexes and for all ages except for TC in the youngest girls. The overall
      prevalence of dyslipidemia was 6.4% in the population-based cohort and 28.0% in
      the cohort with overweight/obesity. The odds ratio for exhibiting dyslipidemia in
      the cohort with overweight/obesity compared with the population-based cohort was
      6.2 (95% CI: 4.9 - 8.1, P < 2*10-16). CONCLUSION: Fasting plasma lipid
      concentrations change during childhood and adolescence and differ with sex and
      age. Children and adolescents with obesity have increased concentrations of
      circulating lipids and exhibit an increased prevalence of dyslipidemia. TRIAL
      REGISTRATION: The study is part of The Danish Childhood Obesity Biobank;
      ClinicalTrials.gov ID-no.: NCT00928473 retrospectively registered on June 25th
      2009.

PMID- 28454531
TI  - The health Oriented pedagogical project (HOPP) - a controlled longitudinal school
      based physical activity intervention program.
AB  - BACKGROUND: The prevalence of non-communicable diseases (NCDs) is increasing
      worldwide, also among children. Information about primary prevention of NCD's is
      increasing; however, convincing strategies among children is needed. The present
      paper describes the design and methods in the Health Oriented Pedagogical Project
      (HOPP) study. The main objective is to evaluate the effects of a school-based
      physical activity intervention program on cardio-metabolic risk factors.
      Secondary objectives include assessment of physical, psychological and academic
      performance variables. METHODS: The HOPP study is a 7 years longitudinal large
      scale controlled intervention in seven elementary schools (n = 1545) with two
      control schools (n = 752); all aged 6-11 years at baseline. The school-based
      physical activity intervention program includes an increase in physical activity
      (PA) of 225 min/week as an integrated part of theoretical learning, in addition
      to the curriculum based 90 min/week of ordinary PA. Primary outcomes include
      cardio-metabolic risk factors measured as PA level, BMI status, waist
      circumference, muscle mass, percent fat, endurance test performance, total serum
      cholesterol, high-density lipoprotein (HDL), non-HDL, micro C-reactive protein
      (mCRP) and long-term blood sugar (HbA1c). In addition, secondary outcomes include
      anthropometric growth measures, physical fitness, quality of life (QoL), mental
      health, executive functions, diet and academic performance. DISCUSSION: HOPP will
      provide evidence of effects on cardio-metabolic risk factors after a long-term PA
      intervention program in elementary schoolchildren. School-based PA intervention
      programs may be an effective arena for health promotion and disease prevention.
      TRIAL REGISTRATION: The study is registered in Clinical trials
      (ClinicalTrials.gov Identifier: NCT02495714 ) as of June 20th - 2015,
      retrospectively registered. The collection of baseline values was initiated in
      mid-January 2015.

PMID- 28454532
TI  - Protocol for the Delirium and Cognitive Impact in Dementia (DECIDE) study: A
      nested prospective longitudinal cohort study.
AB  - BACKGROUND: Delirium is common, affecting at least 20% of older hospital
      inpatients. It is widely accepted that delirium is associated with dementia but
      the degree of causation within this relationship is unclear. Previous studies
      have been limited by incomplete ascertainment of baseline cognition or a lack of
      prospective delirium assessments. There is an urgent need for an improved
      understanding of the relationship between delirium and dementia given that
      delirium prevention may plausibly impact upon dementia prevention. A well
      designed, observational study could also answer fundamental questions of major
      importance to patients and their families regarding outcomes after delirium. The
      Delirium and Cognitive Impact in Dementia (DECIDE) study aims to explore the
      association between delirium and cognitive function over time in older
      participants. In an existing population based cohort aged 65 years and older, the
      effect on cognition of an episode of delirium will be measured, independent of
      baseline cognition and illness severity. The predictive value of clinical
      parameters including delirium severity, baseline cognition and delirium subtype
      on cognitive outcomes following an episode of delirium will also be explored.
      METHODS: Over a 12 month period, surviving participants from the Cognitive
      Function and Ageing Study II-Newcastle will be screened for delirium on admission
      to hospital. At the point of presentation, baseline characteristics along with a
      number of disease relevant clinical parameters will be recorded. The
      progression/resolution of delirium will be monitored. In those with and without
      delirium, cognitive decline and dementia will be assessed at one year follow-up.
      We will evaluate the effect of delirium on cognitive function over time along
      with the predictive value of clinical parameters. DISCUSSION: This study will be
      the first to prospectively elucidate the size of the effect of delirium upon
      cognitive decline and incident dementia. The results will be used to inform
      future dementia prevention trials that focus on delirium intervention.

PMID- 28454533
TI  - Associations between compulsory community treatment and continuity of care in a
      three year follow-up of the Oxford Community Treatment Order Trial (OCTET)
      cohort.
AB  - BACKGROUND: Most studies investigating the effectiveness of Community Treatment
      Orders (CTOs) use readmission to hospital as the primary outcome. Another aim of
      introducing CTOs was to improve continuity of care. Our study was a 3-year
      prospective follow-up which tested for associations between CTOs and continuity
      of care. METHODS: Our study sample included 333 patients recruited to the Oxford
      Community Treatment Order Trial (OCTET). We collected data on continuity of care
      using eight previously operationalized measures. We analysed the association
      between CTOs and continuity of care in two ways. First, we tested the association
      between continuity of care and OCTET randomisation arm (CTO versus voluntary care
      via Section 17 leave). Second, we analysed continuity of care and CTO exposure
      independent of randomisation; using any exposure to CTO, number of days on CTO,
      and proportion of outpatient days on CTO as outcomes. RESULTS: 197 (61%) patients
      were made subject to CTO during the 36-month follow-up. Randomisation to CTO arm
      was significantly associated with having a higher proportion of clinical
      documents copied to the user but no other measures of continuity. Having a higher
      proportion of outpatient days on CTO (irrespective of randomisation) was
      associated with fewer 60 day breaks without community contact. A sensitivity
      analysis found that any exposure to CTO and a higher proportion of outpatient
      days on CTO were associated with fewer days between community mental health team
      contacts and 60 day breaks without contact. CONCLUSION: We found some evidence of
      an association between CTO use and better engagement with the community team in
      terms of increased contact and fewer breaks in care. Those with CTO experience
      had a higher number of inpatient admissions which may have acted as a mediator of
      this association. We found limited evidence for an association between CTO use
      and other measures of continuity of care.

PMID- 28454534
TI  - Palliative care for people with dementia in the terminal phase: a mixed-methods
      qualitative study to inform service development.
AB  - BACKGROUND: When entering the dying phase, the nature of physical, psychosocial
      and spiritual care needs of people with dementia and their families may change.
      Our objective was to understand what needs to be in place to develop optimal
      palliative care services for the terminal phase in the face of a small evidence
      base. METHODS: In 2015-2016, we performed a mixed-methods qualitative study in
      which we (1) analysed the domains and recommendations from the European
      Association for Palliative Care (EAPC) dementia white paper and identified those
      with particular relevance for the terminal phase; (2) performed a series of focus
      group discussions with Dutch family caregivers of people with dementia in
      variable stages; (3) conducted interviews with experts involved in 15 special
      forms of terminal care for people with dementia in five countries. The terminal
      phase was defined as dying but because of the difficulty predicting it, we
      included advanced dementia. We initially analysed the three parts separately,
      followed by an integrated analysis of (1)-(3) to inform service development.
      RESULTS: (1) The EAPC domain of "avoiding overly aggressive, burdensome, or
      futile treatment" was regarded of particular relevance in the terminal phase,
      along with a number of recommendations that refer to providing of comfort. (2)
      Families preferred continuity in care and living arrangements. Despite a
      recognition that this was a time when they had complex support needs, they found
      it difficult to accept involvement of a large team of unfamiliar (professional)
      caregivers. Mostly, terminal care was preferred at the place of residence. (3)
      The expert interviews identified preferred, successful models in which a
      representative of a well-trained team has the time, authority and necessary
      expertise to provide care and education of staff and family to where people are
      and which ensure continuity of relationships with and around the patient.
      CONCLUSION: A mobile team that specializes in palliative care in dementia and
      supports professional and family caregivers is a promising model. Compared to
      transfer to a hospice in the last weeks or days, it has the potential to address
      the priorities of families and patients for continuity of care, relationships and
      specialist expertise.

PMID- 28454535
TI  - Erratum to: Rescue strategy for advanced liver malignancy with retrohepatic
      inferior vena cava thrombi: experience to promote surgical oncological benefit.

PMID- 28454536
TI  - Erratum to: Sophorae Flos extract inhibits RANKL-induced osteoclast
      differentiation by suppressing the NF-kappaB/NFATc1 pathway in mouse bone marrow
      cells.

PMID- 28454537
TI  - Increase in the prevalence of mutations associated with sulfadoxine-pyrimethamine
      resistance in Plasmodium falciparum isolates collected from early to late
      pregnancy in Nanoro, Burkina Faso.
AB  - BACKGROUND: Pregnant women are a high-risk group for Plasmodium falciparum
      infections, which may result in maternal anaemia and low birth weight newborns,
      among other adverse birth outcomes. Intermittent preventive treatment with
      sulfadoxine-pyrimethamine during pregnancy (IPTp-SP) is widely implemented to
      prevent these negative effects of malaria. However, resistance against SP by P.
      falciparum may decrease efficacy of IPTp-SP. Combinations of point mutations in
      the dhps (codons A437, K540) and dhfr genes (codons N51, C59, S108) of P.
      falciparum are associated with SP resistance. In this study the prevalence of SP
      resistance mutations was determined among P. falciparum found in pregnant women
      and the general population (GP) from Nanoro, Burkina Faso and the association of
      IPTp-SP dosing and other variables with mutations was studied. METHODS: Blood
      spots on filter papers were collected from pregnant women at their first
      antenatal care visit (ANC booking) and at delivery, from an ongoing trial and
      from the GP in a cross-sectional survey. The dhps and dhfr genes were amplified
      by nested PCR and products were sequenced to identify mutations conferring
      resistance (ANC booking, n = 400; delivery, n = 223; GP, n = 400). Prevalence was
      estimated with generalized estimating equations and for multivariate analyses
      mixed effects logistic regression was used. RESULTS: The prevalence of the triple
      dhfr mutation was high, and significantly higher in the GP and at delivery than
      at ANC booking, but it did not affect birth weight. Furthermore, quintuple
      mutations (triple dhfr and double dhps mutations) were found for the first time
      in Burkina Faso. IPTp-SP did not significantly affect the occurrence of any of
      the mutations, but high transmission season was associated with increased
      mutation prevalence in delivery samples. It is unclear why the prevalence of
      mutations was higher in the GP than in pregnant women at ANC booking. CONCLUSION:
      The high number of mutants and the presence of quintuple mutants in Burkina Faso
      confirm concerns about the efficacy of IPTp-SP in the near future. Other drug
      combinations to tackle malaria in pregnancy should, therefore, be explored. An
      increase in mutation prevalence due to IPTp-SP dosing could not be confirmed.

PMID- 28454539
TI  - Workplace violence against nurses in the Gambia: mixed methods design.
AB  - BACKGROUND: The aim of this study was to assess the prevalence, perpetrators and
      factors associated with workplace violence against nurses in public secondary
      health care facilities from two health regions in the Gambia. METHODS: Data was
      collected from 219 nurses using self-administered questionnaire and 35 face-to
      face interviews. The data collection was conducted between July and September
      2014 in 14 public secondary health care facilities. RESULTS: A sizable majority
      of respondents (62.1%) reported exposure to violence in the 12 months prior to
      the survey; exposure to verbal abuse, physical violence, and sexual harassment
      was 59.8%, 17.2%, and 10% respectively. The perpetrators were mostly patients'
      escorts/relatives followed by patients themselves. Perceived reasons of workplace
      violence were mainly attributed to nurse-client disagreement, understaffing,
      shortage of drugs and supplies, security vacuum, and lack of management attention
      to workplace violence. CONCLUSIONS: Nurses in the Gambia are at a relatively high
      risk of violent incidents at work. Policies and strategies that are sensitive to
      local circumstances and needs should be developed for the prevention of workplace
      violence.

PMID- 28454538
TI  - Transcriptomic and proteomic insight into the effects of a defined European
      mistletoe extract in Ewing sarcoma cells reveals cellular stress responses.
AB  - BACKGROUND: The hydrophobic triterpenes, oleanolic and betulinic acid as well as
      the hydrophilic mistletoe lectins and viscotoxins possess anticancer properties.
      They do all occur in combination in European mistletoe (Viscum album L.).
      Commercial Viscum album L. extracts are aqueous, excluding the insoluble
      triterpenes. We have previously shown that mistletoe lectins and triterpene acids
      are effective against Ewing sarcoma in vitro, ex vivo and in vivo. METHODS: We
      recreated a total mistletoe effect (viscumTT) by combining an aqueous extract
      (viscum) and a triterpene extract (TT) solubilised with cyclodextrins and
      analysed the effects of viscumTT and the single extracts on TC-71 Ewing sarcoma
      cells in vitro by transcriptomic and proteomic profiling. RESULTS: Treatment with
      the extracts strongly impacted Ewing sarcoma cell gene and protein expression.
      Apoptosis-associated and stress-activated genes were upregulated, proteasomal
      protein abundance enhanced and ribosomal and spliceosomal proteins downregulated.
      The mechanism of action of viscum, TT and viscumTT in TC-71 and MHH-ES-1 cells
      suggests the involvement of the unfolded protein response. While viscum and
      viscumTT extract treatment indicate response to oxidative stress and activation
      of stress-mediated MAPK signalling, TT extract treatment suggests the involvement
      of TLR signalling and autophagy. CONCLUSIONS: Since the combinatory extract
      viscumTT exerts highly effective pro-apoptotic effects on Ewing sarcoma cells in
      vitro, this phytopolychemotherapy could be a promising adjuvant therapeutic
      option for paediatric patients with Ewing sarcoma.

PMID- 28454540
TI  - Low physical activity, high television viewing and poor sleep duration cluster in
      overweight and obese adults; a cross-sectional study of 398,984 participants from
      the UK Biobank.
AB  - BACKGROUND: An unhealthy lifestyle is one of the greatest contributors to
      obesity. A number of behaviours are linked with obesity, but are often measured
      separately. The UK Biobank cohort of >500,000 participants allows us to explore
      these behaviours simultaneously. We therefore aimed to compare physical activity,
      television (TV) viewing and sleep duration across body mass index (BMI)
      categories in a large sample of UK adults. METHODS: UK Biobank participants were
      recruited and baseline measures were taken between 2007 and 2010 and data
      analysis was performed in 2015. BMI was measured objectively using trained staff.
      Self-report questionnaires were used to measure lifestyle behaviours including
      the international physical activity questionnaire (IPAQ-short form) for physical
      activity. During data analysis, six groups were defined based on BMI;
      'Underweight' (n = 2026), 'Normal weight' (n = 132,372), 'Overweight (n =
      171,030), 'Obese I' (n = 67,903), 'Obese II' (n = 18,653) and 'Obese III' (n =
      7000). The odds of reporting unhealthy lifestyle behaviours (low physical
      activity, high TV viewing or poor sleep duration) were compared across BMI groups
      using logistic regression analysis. RESULTS: Overweight and obese adults were
      more likely to report low levels of physical activity (<=967.5 MET.mins/wk)
      ('Overweight'-OR [95% CI]: 1.23 [1.20 to 1.26], 'Obese I' 1.66 [1.61-1.71],
      'Obese II' 2.21 [2.12-2.30], and 'Obese III' 3.13 [2.95 to 3.23]) compared to
      'Normal weight' adults. The odds of reporting high TV viewing (3 h/day) was
      greater in 'Overweight' (1.52 [1.48 to 1.55]) and obese adults ('Obese I' 2.06
      [2.00-2.12], 'Obese II' 2.69 [2.58-2.80], 'Obese III' 3.26 [3.07 to 3.47]), and
      poor sleep duration (<7, >8 h/night) was higher in 'Overweight' (1.09 [1.07 to
      1.12]) and obese adults ('Obese I' 1.31 [1.27-1.34], 'Obese II' 1.50 [1.44-1.56],
      'Obese III' (1.78 [1.68 to 1.89]) compared to the 'Normal weight' group. These
      lifestyle behaviours were clustered, the odds of reporting simultaneous low
      physical activity, high TV viewing and poor sleep (unhealthy behavioural
      phenotype) was higher than reporting these behaviours independently, in
      overweight and obese groups. 'Obese III' adults were almost six times more likely
      (5.47 [4.96 to 6.05]) to report an unhealthy behavioural phenotype compared to
      the 'Normal weight' group. CONCLUSIONS: Overweight and obese adults report low
      levels of physical activity, high TV viewing and poor sleep duration. These
      behaviours seem to cluster and collectively expose individuals to greater risk of
      obesity. Multiple lifestyle behaviours should be targeted in future
      interventions.

PMID- 28454541
TI  - Relationship between activity limitation and health-related quality of life in
      school-aged children with cerebral palsy: a cross-sectional study.
AB  - BACKGROUND: Information on health-related quality of life is becoming
      increasingly important in children with cerebral palsy. This study investigated
      the relationship between activity limitation and health-related quality of life
      in school-aged children with cerebral palsy. METHODS: Data were collected from 71
      children aged 6-15 years with cerebral palsy. Activity limitations were assessed
      using functional classification systems, including the Korean-Gross Motor
      Function Classification System (K-GMFCS) and the Korean-Manual Ability
      Classification System (K-MACS). Health-related quality of life was assessed using
      the Korean version of the Childhood Health Assessment Questionnaire. Physical
      therapists collected the data by interviewing the parents of the subjects.
      RESULTS: Both the K-GMFCS and the K-MACS were significantly positively correlated
      with the Childhood Health Assessment Questionnaire. The Childhood Health
      Assessment Questionnaire score differed significantly with respect to the
      functional classification systems. The differences in the ratings according to
      the K-GMFCS levels were significant, except those between levels I and II, levels
      II and III, levels III and IV, and levels IV and V. In the K-MACS, there were no
      significant differences between levels I and II, levels III and IV, and levels IV
      and V. The K-GMFCS and the K-MACS were significant predictors of health-related
      quality of life, demonstrating 75.5% of the variance (p < 0.05). CONCLUSION:
      Comprehensive information on children with cerebral palsy should be gathered to
      provide professionals with a better understanding of health-related quality of
      life.

PMID- 28454542
TI  - Perilipins: a diversity of intracellular lipid droplet proteins.
AB  - Intracellular lipid droplets (LDs) are found in a wide variety of cell types and
      have been recognized as organelles with unique spherical structures. Although LDs
      are not stable lipid-depots, they are active sites of neutral lipid metabolism,
      and comprise neutral lipid or cholesterol cores surrounded by phospholipid
      monolayers containing specialized proteins. However, sizes and protein
      compositions vary between cell and tissue types. Proteins of the perilipin family
      have been associated with surfaces of LDs and all carry a conserved 11-mer repeat
      motif. Accumulating evidence indicates that all perilipins are involved in LD
      formation and that all play roles in LD function under differing conditions. In
      this brief review, we summarize current knowledge of the roles of perilipins and
      lipid metabolizing enzymes in a variety of mammalian cell types.

PMID- 28454544
TI  - Attenuation of acute lung injury in a rat model by Semen Cassiae.
AB  - BACKGROUND: Acute lung injury (ALI) is an inflammatory disorder. Semen Cassiae
      has potent anti-inflammatory activities. The aim of our study was to investigate
      whether Semen Cassiae plays a protective effect on lipopolysaccharide (LPS)
      induced ALI and, if so, to elucidate its potential mechanism. METHODS: Male
      Sprague-Dawley rat lungs were injured by intratracheal instillation of LPS. Rats
      were treated with Semen Cassiae or vehicle 3 h after LPS challenge. Samples were
      harvested 24 h post-LPS administration. We also investigated the effects of Semen
      Cassiae on LPS stimulation in RAW 264.7 cells. RESULTS: LPS administration
      markedly induced pulmonary edema and polymorphonuclear neutrophil influxes. These
      changes were significantly attenuated in Semen Cassiae treated group. Moreover,
      Semen Cassiae markedly reduced pulmonary interleukin (IL)-6, tumor necrosis
      factor (TNF)-alpha, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. The
      pulmonary soluble epoxide hydrolase (sEH) activity and the DNA binding activity
      of Nuclear factor (NF)-kappaB were significantly inhibited in Semen Cassiae
      treated group. Furthermore, Semen Cassiae treatment significantly increased
      epoxyeicosatrienoic acids (EETs), and heme oxygenase-1 (HO-1) activity. Our in
      vitro study demonstrates that Semen Cassiae treatment may inhibit LPS induced
      IkappaBalpha phosphorylation and NF-kappaB p65 nucleus translocation. CONCLUSION:
      Semen Cassiae protects LPS-induced ALI in rats. Semen Cassiae can be developed as
      a novel treatment for ALI.

PMID- 28454543
TI  - TREM-1 associated macrophage polarization plays a significant role in inducing
      insulin resistance in obese population.
AB  - BACKGROUND: TREM-1 acts as an amplifier of inflammation expressed on macrophages.
      The objective of this study was to evaluate the relationship between TREM-1 and
      macrophage polarization, and association of TREM-1 and M1 macrophage polarization
      with insulin resistance (IR) in obese population compared to non-obese
      population. METHODS: We enrolled 38 patients after obtaining IRB approval for
      this study. We evaluated the mRNA and protein expression levels of general
      macrophage marker (CD68), M1 marker (CD86, CCR7, iNOS, IFNgamma, TNF-alpha and IL
      6,), M2 marker (CD206, CD163, IL-10, IL-4) and chemokine axis (MCP-1, CCR2 and
      CCR5) along with TREM-1 and TREM-2 in omentum fat, subcutaneous fat, and liver
      biopsy tissues of non-obese (N = 5), obese non-diabetics, (N = 16) and obese
      diabetics (N = 17). RESULTS: The results of our study showed over-expression of
      TREM-1, M1 markers and down-regulation of TREM-2 and M2 markers in the omentum,
      subcutaneous and liver biopsies of obese patients (diabetics and non-diabetics)
      compared to non-obese patients. Overall, the obese diabetic group showed a
      significant (p < 0.05) higher number of patients with over expression of M1
      markers (TREM-1, CD68, CD86, CCR-7, iNOS, IFN-gamma, TNF-alpha, IL-6, MCP-1, CCR
      2 and CCR-5) and down-regulation of M2 markers (CD206, CD163 and IL-4) in liver
      biopsy compared to obese non-diabetics. CONCLUSIONS: TREM-1 expression is
      significantly increased along with the M1 markers in liver biopsy of obese
      diabetic (17/17) and obese non-diabetic patients (9/16). Our data suggests that
      TREM-1 overexpression and M1 macrophage polarization are associated with obesity
      induced IR.

PMID- 28454545
TI  - Cleavage modification did not alter blastomere fates during bryozoan evolution.
AB  - BACKGROUND: Stereotypic cleavage patterns play a crucial role in cell fate
      determination by precisely positioning early embryonic blastomeres. Although
      misplaced cell divisions can alter blastomere fates and cause embryonic defects,
      cleavage patterns have been modified several times during animal evolution.
      However, it remains unclear how evolutionary changes in cleavage impact the
      specification of blastomere fates. Here, we analyze the transition from spiral
      cleavage - a stereotypic pattern remarkably conserved in many protostomes - to a
      biradial cleavage pattern, which occurred during the evolution of bryozoans.
      RESULTS: Using 3D-live imaging time-lapse microscopy (4D-microscopy), we
      characterize the cell lineage, MAPK signaling, and the expression of 16
      developmental genes in the bryozoan Membranipora membranacea. We found that the
      molecular identity and the fates of early bryozoan blastomeres are similar to the
      putative homologous blastomeres in spiral-cleaving embryos. CONCLUSIONS: Our work
      suggests that bryozoans have retained traits of spiral development, such as the
      early embryonic fate map, despite the evolution of a novel cleavage geometry.
      These findings provide additional support that stereotypic cleavage patterns can
      be modified during evolution without major changes to the molecular identity and
      fate of embryonic blastomeres.

PMID- 28454546
TI  - Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple
      blood-stage proteins in a low-transmission region of western Thailand.
AB  - BACKGROUND: Thailand is aiming to eliminate malaria by the year 2024. Plasmodium
      vivax has now become the dominant species causing malaria within the country, and
      a high proportion of infections are asymptomatic. A better understanding of
      antibody dynamics to P. vivax antigens in a low-transmission setting, where
      acquired immune responses are poorly characterized, will be pivotal for
      developing new strategies for elimination, such as improved surveillance methods
      and vaccines. The objective of this study was to characterize total IgG antibody
      levels to 11 key P. vivax proteins in a village of western Thailand. METHODS:
      Plasma samples from 546 volunteers enrolled in a cross-sectional survey conducted
      in 2012 in Kanchanaburi Province were utilized. Total IgG levels to 11 different
      proteins known or predicted to be involved in reticulocyte binding or invasion
      (ARP, GAMA, P41, P12, PVX_081550, and five members of the PvRBP family), as well
      as the leading pre-erythrocytic vaccine candidate (CSP) were measured using a
      multiplexed bead-based assay. Associations between IgG levels and infection
      status, age, and spatial location were explored. RESULTS: Individuals from a low
      transmission region of western Thailand reacted to all 11 P. vivax recombinant
      proteins. Significantly greater IgG levels were observed in the presence of a
      current P. vivax infection, despite all infected individuals being asymptomatic.
      IgG levels were also higher in adults (18 years and older) than in children. For
      most of the proteins, higher IgG levels were observed in individuals living
      closer to the Myanmar border and further away from local health services.
      CONCLUSIONS: Robust IgG responses were observed to most proteins and IgG levels
      correlated with surrogates of exposure, suggesting these antigens may serve as
      potential biomarkers of exposure, immunity, or both.

PMID- 28454548
TI  - Effective communication of public health guidance to emergency department
      clinicians in the setting of emerging incidents: a qualitative study and
      framework.
AB  - BACKGROUND: Evidence to inform communication between emergency department
      clinicians and public health agencies is limited. In the context of diverse,
      emerging public health incidents, communication is urgent, as emergency
      department clinicians must implement recommendations to protect themselves and
      the public. The objectives of this study were to: explore current practices,
      barriers and facilitators at the local level for communicating public health
      guidance to emergency department clinicians in emerging public health incidents;
      and develop a framework that promotes effective communication of public health
      guidance to clinicians during emerging incidents. METHODS: A qualitative study
      was conducted using semi-structured interviews with 26 key informants from
      emergency departments and public health agencies in Ontario, Canada. Data were
      analyzed inductively and the analytic approach was guided by concepts of
      complexity theory. RESULTS: Emergent themes corresponded to challenges and
      strategies for effective communication of public health guidance. Important
      challenges related to the coordination of communication across institutions and
      jurisdictions, and differences in work environments across sectors. Strategies
      for effective communication were identified as the development of partnerships
      and collaboration, attention to specific methods of communication used, and the
      importance of roles and relationship-building prior to an emerging public health
      incident. Following descriptive analysis, a framework was developed that consists
      of the following elements: 1) Anticipate; 2) Invest in building relationships and
      networks; 3) Establish liaison roles and redundancy; 4) Active communication; 5)
      Consider and respond to the target audience; 6) Leverage networks for
      coordination; and 7) Acknowledge and address uncertainty. The qualities inherent
      in local relationships cut across framework elements. CONCLUSIONS: This research
      indicates that relationships are central to effective communication between
      public health agencies and emergency department clinicians at the local level.
      Our framework which is grounded in qualitative evidence focuses on strategies to
      promote effective communication in the emerging public health incident setting
      and may be useful in informing practice.

PMID- 28454547
TI  - PARP1 expression drives the synergistic antitumor activity of trabectedin and
      PARP1 inhibitors in sarcoma preclinical models.
AB  - BACKGROUND: Enhancing the antitumor activity of the DNA-damaging drugs is an
      attractive strategy to improve current treatment options. Trabectedin is an
      isoquinoline alkylating agent with a peculiar mechanism of action. It binds to
      minor groove of DNA inducing single- and double-strand-breaks. These kinds of
      damage lead to the activation of PARP1, a first-line enzyme in DNA-damage
      response pathways. We hypothesized that PARP1 targeting could perpetuate
      trabectedin-induced DNA damage in tumor cells leading finally to cell death.
      METHODS: We investigated trabectedin and PARP1 inhibitor synergism in several
      tumor histotypes both in vitro and in vivo (subcutaneous and orthotopic tumor
      xenografts in mice). We searched for key determinants of drug synergism by
      comparative genomic hybridization (aCGH) and gene expression profiling (GEP) and
      validated their functional role. RESULTS: Trabectedin activated PARP1 enzyme and
      the combination with PARP1 inhibitors potentiated DNA damage, cell cycle arrest
      at G2/M checkpoint and apoptosis, if compared to single agents. Olaparib was the
      most active PARP1 inhibitor to combine with trabectedin and we confirmed the
      antitumor and antimetastatic activity of trabectedin/olaparib combination in mice
      models. However, we observed different degree of trabectedin/olaparib synergism
      among different cell lines. Namely, in DMR leiomyosarcoma models the combination
      was significantly more active than single agents, while in SJSA-1 osteosarcoma
      models no further advantage was obtained if compared to trabectedin alone. aCGH
      and GEP revealed that key components of DNA-repair pathways were involved in
      trabectedin/olaparib synergism. In particular, PARP1 expression dictated the
      degree of the synergism. Indeed, trabectedin/olaparib synergism was increased
      after PARP1 overexpression and reduced after PARP1 silencing. CONCLUSIONS: PARP1
      inhibition potentiated trabectedin activity in a PARP1-dependent manner and PARP1
      expression in tumor cells might be a useful predictive biomarker that deserves
      clinical evaluation.

PMID- 28454549
TI  - Does age really matter? Radiotherapy in elderly patients with glioblastoma, the
      Munich experience.
AB  - BACKGROUND: Glioblastoma is usually diagnosed around the age of 60-70 years.
      Patients older than 65 years are frequently described as "elderly". Several
      trials with monotherapy have established treatment regimens that offer therapies
      with reduced side effects but reduced efficacy. We analysed the outcome of
      elderly glioblastoma patients treated at our facility. METHODS: We performed a
      retrospective analysis of 62 consecutive patients older than 65 years treated for
      a primary glioblastoma at our facility from 2009 to 2015. RESULTS: Median age was
      69.6 years (range 65.1-85.6 years); median OS of the entire cohort was 10.9
      months. ECOG, MGMT and extent of resection but not age and the time from surgery
      to radiotherapy were associated with longer survival. Patients treated with
      adjuvant chemotherapy had a significantly longer survival (20.5 vs. 7.8 months).
      Furthermore, salvage therapies were associated with significant improved survival
      when compared to Best Supportive Care (22.3 vs. 8.8 months). CONCLUSION: Also
      elderly patients are likely to benefit from an aggressive treatment after primary
      diagnosis of glioblastoma.

PMID- 28454550
TI  - Occupational factors and low back pain: a cross-sectional study of Bangladeshi
      female nurses.
AB  - BACKGROUND: The suffering from low back pain (LBP) is very common among nurses.
      The high prevalence rates of LBP are observed in many countries. Many back
      injuries are due to individual and work-related factors. Our aim is to
      investigate whether there is an association of occupational factors with LBP
      among the female nurses who are currently working in tertiary hospitals of
      Bangladesh. METHODS: We conducted a cross-sectional study with 229 female nurses
      from two selected tertiary hospitals in Bangladesh. Data was collected through
      face-to-face interview using a standard structured questionnaire on four
      different measures of LBP along with questions on socio-demographic, occupational
      factors, physical and psychological factors. RESULTS: Prevalence rates of LBP
      that lasted for at least 1 day, chronic LBP, intense pain and sought medical care
      because of LBP during the last 12 months were 72.9, 31.8, 24.4 and 36.2%,
      respectively. The multiple logistic regression analyses indicates that
      insufficient supporting staffs, overtime working hours and manual lifting in a
      working environment are associated with LBP. Besides, age and parity are found
      positively associated with chronic LBP. CONCLUSION: The prevalence of LBP among
      nurses in Bangladesh is high and should be actively addressed. Certain
      occupational factors play a key role in developing LBP among nurses. Nurses to
      patients ratio should be taken into consideration to reduce the occurrence of LBP
      among nurses employed in hospitals.

PMID- 28454551
TI  - Mitochondrial DNA mutations in Parkinson's disease brain.

PMID- 28454552
TI  - How common is ponticulus posticus on lateral cephalograms?
AB  - BACKGROUND: Ponticulus posticus is an anomaly of first cervical vertebra visible
      on lateral cephalogram and has some serious medical and surgical implications.
      Unfortunately, it is often overlooked or undetected by orthodontists. The general
      objective of this study is to sensitize orthodontists about this anomaly by
      depicting its prevalence among a group of Nepalese orthodontic patients. METHODS:
      Four hundred and fourteen digital lateral cephalograms of orthodontic patients
      were retrieved from the archives of the department. The lateral cephalograms were
      carefully assessed for the presence of ponticulus posticus in the posterior spine
      of atlas vertebra by two investigators independently and the findings were
      recorded. RESULTS: Ponticulus posticus was observed in 35.7% of the cases, of
      which 30.9% had partial ponticulus posticus and 4.8% had complete ponticulus
      posticus. Even though there was some female predilection, no statistically
      significant association was found between gender of the patient and presence of
      ponticulus posticus. CONCLUSION: Ponticulus posticus is a fairly common anomaly
      with more than one-third (35.7%) of a group of Nepalese orthodontic patients
      affected and is independent of gender. Since, this anomaly is associated with
      numerous medical conditions and has surgical implications, orthodontists should
      use lateral cephalogram as screening radiograph for this anomaly.

PMID- 28454553
TI  - Ambulatory oxygen in fibrotic lung disease (AmbOx): study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Fibrotic interstitial lung diseases (ILDs) are chronic and often
      progressive conditions resulting in substantial morbidity and mortality.
      Shortness of breath, a symptom often linked to oxygen desaturation on exertion,
      is tightly linked to worsening quality of life in these patients. Although
      ambulatory oxygen is used empirically in their treatment, there are no ILD
      specific guidelines on its use. To our knowledge, no studies are available on the
      effects of ambulatory oxygen on day-to-day life in patients with ILD.
      METHODS/DESIGN: Ambulatory oxygen in fibrotic lung disease (AmbOx) is a
      multicentre, randomised controlled crossover trial (RCT) funded by the Research
      for Patient Benefit Programme of the National Institute for Health Research. The
      trial will compare ambulatory oxygen used during daily activities with no
      ambulatory oxygen in patients with fibrotic lung disease whose oxygen saturation
      (SaO2) is >=94% at rest, but drops to <=88% on a 6-min Walk Test. The randomised
      controlled trial (RCT) will evaluate the effects on health status (measured by
      the King's Brief ILD Questionnaire: K-BILD) of ambulatory oxygen used at home, at
      an optimal flow rate determined by titration at screening visit, and administered
      for a 2-week period, compared to 2 weeks off oxygen. Key secondary outcomes will
      include breathlessness on activity scores, as measured by the University of
      California San Diego Shortness of Breath Questionnaire, global patient assessment
      of change scores, as well as quality of life scores (St George's Respiratory
      Questionnaire), anxiety and depression scores (Hospital Anxiety and Depression
      Scale), activity markers measured by SenseWear Armbands, pulse oximetry
      measurements, patient-reported daily activities, patient- and oxygen company
      reported oxygen cylinder use. The study also includes a qualitative component and
      will explore in interviews patients' experiences of the use of a portable oxygen
      supply and trial participation in a subgroup of 20 patients and carers.
      DISCUSSION: This is the first RCT of the effects of ambulatory oxygen during
      daily life on health status and breathlessness in fibrotic lung disease. The
      results generated should provide the basis for setting up ILD-specific guidelines
      for the use of ambulatory oxygen. TRIAL REGISTRATION: National Clinical Trials
      Registry, identifier: NCT02286063 . Registered on 8 October 2014 (retrospectively
      registered).

PMID- 28454554
TI  - Impaired lysosomal activity mediated autophagic flux disruption by graphite
      carbon nanofibers induce apoptosis in human lung epithelial cells through
      oxidative stress and energetic impairment.
AB  - BACKGROUND: Graphite carbon nanofibers (GCNF) have emerged as a potential
      alternative of carbon nanotubes (CNT) for various biomedical applications due to
      their superior physico-chemical properties. Therefore in-depth understanding of
      the GCNF induced toxic effects and underlying mechanisms in biological systems is
      of great interest. Currently, autophagy activation by nanomaterials is recognized
      as an emerging toxicity mechanism. However, the association of GCNF induced
      toxicity with this form of cell death is largely unknown. In this study, we have
      assessed the possible mechanism; especially the role of autophagy, underlying the
      GCNF induced toxicity. METHODS: Human lung adenocarcinoma (A549) cells were
      exposed to a range of GCNF concentrations and various cellular parameters were
      analyzed (up to 48 h). Transmission electron microscopy, immunofluorescent
      staining, western blot and quantitative real time PCR were performed to detect
      apoptosis, autophagy induction, lysosomal destabilization and cytoskeleton
      disruption in GCNF exposed cells. DCFDA assay was used to evaluate the reactive
      oxygen species (ROS) production. Experiments with N-acetyl-L-cysteine (NAC), 3
      methyladenine (3-MA) and LC3 siRNA was carried out to confirm the involvement of
      oxidative stress and autophagy in GCNF induced cell death. Comet assay and
      micronucleus (MN) assay was performed to assess the genotoxicity potential.
      RESULTS: In the present study, GCNF was found to induce nanotoxicity in human
      lung cells through autophagosomes accumulation followed by apoptosis via
      intracellular ROS generation. Mechanistically, impaired lysosomal function and
      cytoskeleton disruption mediated autophagic flux blockade was found to be the
      major cause of accumulation rather than autophagy induction which further
      activates apoptosis. The whole process was in line with the increased ROS level
      and their pharmacological inhibition leads to mitigation of GCNF induced cell
      death. Moreover the inhibition of autophagy attenuates apoptosis indicating the
      role of autophagy as cell death process. GCNF was also found to induce genomic
      instability. CONCLUSION: Our present study demonstrates that GCNF perturbs
      various interrelated signaling pathway and unveils the potential nanotoxicity
      mechanism of GCNF through targeting ROS-autophagy-apoptosis axis. The current
      study is significant to evaluate the safety and risk assessment of fibrous carbon
      nanomaterials prior to their potential use and suggests caution on their
      utilization for biomedical research.

PMID- 28454556
TI  - Molecular and epidemiological characterization of HIV-1 subtypes among Libyan
      patients.
AB  - BACKGROUND: The epidemiological and clinical aspects of human immunodeficiency
      virus subtypes are of great interest worldwide. These subtypes are rarely studied
      in North African countries. Libya is a large country with the longest coast on
      the Mediterranean Sea, facing the Southern European countries. Studies on the
      characterization of HIV-1 subtypes are limited in Libya. This study aimed to
      determine the magnitude of the HIV problem among the Libyan population and to
      better understand the genetic diversity and the epidemiologic dynamics of HIV 1,
      as well as to correlate that with the risk factors involved. METHODS: A total of
      159 HIV-1 strains were collected from 814 HIV positive patients from the four
      Libyan regions during a 16-year period (1995-2010). To determine the HIV-1
      subtypes, genetic analysis and molecular sequencing were carried out using
      provirus polygene. Epidemiologic and demographic information was obtained from
      each participant and correlated with HIV-1 subtypes using logistic regression.
      RESULTS: The overall prevalence of HIV among Libyans ranged from 5 to 10 per
      100,000 during the study period. It was higher among intravenous drug users
      (IVDUs) (53.9%), blood recipients (25.9%) and heterosexuals (17.6%) than by
      vertical transmission (2.6%). Prevalence was higher among males aged 20-40 years
      (M:F 1:6, P > 0.001). Among the 159 strains of HIV-1 available for typing, 117
      strains (73.6%) were subtype B, 29 (18.2%) were CRF02_AG, and 13 (8.2%) were
      subtype A. HIV-1 subtype B was the most prevalent all over the country, and it
      was more prevalent in the Northern region, particularly among IVDUs (P < 0.001).
      GRF02_AG was common in the Eastern region, particularly among blood recipients
      while subtype A emerged in the Western region, particularly among IVDUs.
      CONCLUSIONS: HIV-1 infection is emerging in Libya with a shifting prevalence of
      subtypes associated with the changing epidemiology of HIV-1 among risk groups. A
      genetic analysis of HIV-1 strains demonstrated low subtype heterogeneity with the
      evolution of subtype B, and CRF_20 AG, as well as HIV-1 subtype A. Our study
      highlights the importance of expanded surveillance programs to control HIV
      infection and the necessity of introducing public health strategies to target the
      risk groups, particularly IVDUs.

PMID- 28454555
TI  - A critical assessment of the "sterile womb" and "in utero colonization"
      hypotheses: implications for research on the pioneer infant microbiome.
AB  - After more than a century of active research, the notion that the human fetal
      environment is sterile and that the neonate's microbiome is acquired during and
      after birth was an accepted dogma. However, recent studies using molecular
      techniques suggest bacterial communities in the placenta, amniotic fluid, and
      meconium from healthy pregnancies. These findings have led many scientists to
      challenge the "sterile womb paradigm" and propose that microbiome acquisition
      instead begins in utero, an idea that would fundamentally change our
      understanding of gut microbiota acquisition and its role in human development. In
      this review, we provide a critical assessment of the evidence supporting these
      two opposing hypotheses, specifically as it relates to (i) anatomical,
      immunological, and physiological characteristics of the placenta and fetus; (ii)
      the research methods currently used to study microbial populations in the
      intrauterine environment; (iii) the fecal microbiome during the first days of
      life; and (iv) the generation of axenic animals and humans. Based on this
      analysis, we argue that the evidence in support of the "in utero colonization
      hypothesis" is extremely weak as it is founded almost entirely on studies that
      (i) used molecular approaches with an insufficient detection limit to study "low
      biomass" microbial populations, (ii) lacked appropriate controls for
      contamination, and (iii) failed to provide evidence of bacterial viability. Most
      importantly, the ability to reliably derive axenic animals via cesarean sections
      strongly supports sterility of the fetal environment in mammals. We conclude that
      current scientific evidence does not support the existence of microbiomes within
      the healthy fetal milieu, which has implications for the development of clinical
      practices that prevent microbiome perturbations after birth and the establishment
      of future research priorities.

PMID- 28454558
TI  - Response to Simon et al.

PMID- 28454557
TI  - Longitudinal genomic surveillance of Plasmodium falciparum malaria parasites
      reveals complex genomic architecture of emerging artemisinin resistance.
AB  - BACKGROUND: Artemisinin-based combination therapies are the first line of
      treatment for Plasmodium falciparum infections worldwide, but artemisinin
      resistance has risen rapidly in Southeast Asia over the past decade. Mutations in
      the kelch13 gene have been implicated in this resistance. We used longitudinal
      genomic surveillance to detect signals in kelch13 and other loci that contribute
      to artemisinin or partner drug resistance. We retrospectively sequenced the
      genomes of 194 P. falciparum isolates from five sites in Northwest Thailand, over
      the period of a rapid increase in the emergence of artemisinin resistance (2001
      2014). RESULTS: We evaluate statistical metrics for temporal change in the
      frequency of individual SNPs, assuming that SNPs associated with resistance
      increase in frequency over this period. After Kelch13-C580Y, the strongest
      temporal change is seen at a SNP in phosphatidylinositol 4-kinase, which is
      involved in a pathway recently implicated in artemisinin resistance. Furthermore,
      other loci exhibit strong temporal signatures which warrant further investigation
      for involvement in artemisinin resistance evolution. Through genome-wide
      association analysis we identify a variant in a kelch domain-containing gene on
      chromosome 10 that may epistatically modulate artemisinin resistance.
      CONCLUSIONS: This analysis demonstrates the potential of a longitudinal genomic
      surveillance approach to detect resistance-associated gene loci to improve our
      mechanistic understanding of how resistance develops. Evidence for additional
      genomic regions outside of the kelch13 locus associated with artemisinin
      resistant parasites may yield new molecular markers for resistance surveillance,
      which may be useful in efforts to reduce the emergence or spread of artemisinin
      resistance in African parasite populations.

PMID- 28454559
TI  - Dose tracking assessment for image-guided radiotherapy of the prostate bed and
      the impact on clinical workflow.
AB  - BACKGROUND: The cumulative dose was compared with the planned dose among fourteen
      patients undergoing image-guided, intensity-modulated radiotherapy of the
      prostate bed. Moreover, we investigated the feasibility of adding dose tracking
      to the routine workflow for radiotherapy. METHODS: Daily cone beam computed
      tomography was conducted for image-guided radiotherapy, and weekly cumulative
      delivered doses were calculated for dose tracking. Deformable image registration
      was applied to map weekly dose distributions to the original treatment plan and
      to create a cumulative dose distribution. The dose-volume histogram (DVH) cut-off
      points for the rectum and bladder and the planning target volume (PTV), were used
      to compare the planned and cumulative delivered doses. The additional time
      required by the departmental staff to complete these duties was recorded.
      RESULTS: The PTV coverage of the delivered treatment did not satisfy the expected
      goal for three patients (V98% >98%). In another three patients, the DVH cut-off
      point for the bladder was higher than the limits, while for the rectum, treatment
      was as expected in all cases (two patients failed both their bladder constraints
      and the PTV coverage). Overall, four patients did not satisfy one or more
      criteria at the end of their treatment. CONCLUSIONS: A well-defined strategy for
      dose tracking assessment is feasible, would have minimal impact on the workload
      of a radiotherapy department, and may offer objective information to support
      radiation oncologists in making decisions about adaptive procedures.

PMID- 28454560
TI  - Fecal shedding and tissue infections demonstrate transmission of Mycobacterium
      avium subsp. paratuberculosis in group-housed dairy calves.
AB  - Current Johne's disease control programs primarily focus on decreasing
      transmission of Mycobacterium avium subsp. paratuberculosis (MAP) from infectious
      adult cows to susceptible calves. However, potential transmission between calves
      is largely overlooked. The objective was to determine the extent of MAP infection
      in calves contact-exposed to infectious penmates. Thirty-two newborn Holstein
      Friesian calves were grouped into 7 experimental groups of 4, consisting of 2
      inoculated (IN) calves, and 2 contact-exposed (CE) calves, and 1 control pen with
      4 non-exposed calves. Calves were group housed for 3 months, with fecal samples
      were collected 3 times per week, blood and environmental samples weekly, and
      tissue samples at the end of the trial. The IN calves exited the trial after 3
      months of group housing, whereas CE calves were individually housed for an
      additional 3 months before euthanasia. Control calves were group-housed for the
      entire trial. All CE and IN calves had MAP-positive fecal samples during the
      period of group housing; however, fecal shedding had ceased at time of individual
      housing. All IN calves had MAP-positive tissue samples at necropsy, and 7 (50%)
      of the CE had positive tissue samples. None of the calves had a humoral immune
      response, whereas INF-gamma responses were detected in all IN calves and 5 (36%)
      CE calves. In conclusion, new MAP infections occurred due to exposure of
      infectious penmates to contact calves. Therefore, calf-to-calf transmission is a
      potential route of uncontrolled transmission on cattle farms.

PMID- 28454561
TI  - A comprehensive multi-omics approach uncovers adaptations for growth and survival
      of Pseudomonas aeruginosa on n-alkanes.
AB  - BACKGROUND: Examination of complex biological systems has long been achieved
      through methodical investigation of the system's individual components. While
      informative, this strategy often leads to inappropriate conclusions about the
      system as a whole. With the advent of high-throughput "omic" technologies,
      however, researchers can now simultaneously analyze an entire system at the level
      of molecule (DNA, RNA, protein, metabolite) and process (transcription,
      translation, enzyme catalysis). This strategy reduces the likelihood of improper
      conclusions, provides a framework for elucidation of genotype-phenotype
      relationships, and brings finer resolution to comparative genomic experiments.
      Here, we apply a multi-omic approach to analyze the gene expression profiles of
      two closely related Pseudomonas aeruginosa strains grown in n-alkanes or
      glycerol. RESULTS: The environmental P. aeruginosa isolate ATCC 33988 consumed
      medium-length (C10-C16) n-alkanes more rapidly than the laboratory strain PAO1,
      despite high genome sequence identity (average nucleotide identity >99%). Our
      data shows that ATCC 33988 induces a characteristic set of genes at the
      transcriptional, translational and post-translational levels during growth on
      alkanes, many of which differ from those expressed by PAO1. Of particular
      interest was the lack of expression from the rhl operon of the quorum sensing
      (QS) system, resulting in no measurable rhamnolipid production by ATCC 33988.
      Further examination showed that ATCC 33988 lacked the entire lasI/lasR arm of the
      QS response. Instead of promoting expression of QS genes, ATCC 33988 up-regulates
      a small subset of its genome, including operons responsible for specific alkaline
      proteases and sphingosine metabolism. CONCLUSION: This work represents the first
      time results from RNA-seq, microarray, ribosome footprinting, proteomics, and
      small molecule LC-MS experiments have been integrated to compare gene expression
      in bacteria. Together, these data provide insights as to why strain ATCC 33988 is
      better adapted for growth and survival on n-alkanes.

PMID- 28454562
TI  - Diagnosis and outcomes of acute kidney injury using surrogate and imputation
      methods for missing preadmission creatinine values.
AB  - BACKGROUND: Missing preadmission serum creatinine (SCr) values are a common
      obstacle to assess acute kidney injury (AKI) diagnosis and outcomes. The Kidney
      Disease Improving Global Outcomes (KDIGO) guidelines suggest using a SCr computed
      from the Modification of Diet in Renal Disease (MDRD) with an estimated
      glomerular filtration rate of 75 ml/min/1.73 m2. We aimed to identify the best
      surrogate method for baseline SCr to assess AKI diagnosis and outcomes. METHODS:
      We compared the use of 1) first SCr at hospital admission 2) minimal SCr over 2
      weeks after intensive care unit admission 3) MDRD computed SCr and 4) Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) computed SCr to assess AKI
      diagnosis and outcomes. We then performed multilinear regression models to
      predict preadmission SCr and imputation strategies to assess AKI diagnosis.
      RESULTS: Our one-year retrospective cohort study included 1001 critically ill
      adults; 498 of them had preadmission SCr values. In these patients, AKI incidence
      was 25.1% using preadmission SCr. First SCr had the best agreement for AKI
      diagnosis (22.5%; kappa = 0.90) and staging (kappa = 0.81). MDRD, CKD-EPI and
      minimal SCr overestimated AKI diagnosis (26.7%, 27.1% and 43.2%;kappa = 0.86,
      0.86 and 0.60, respectively). However, MDRD and CKD-EPI computed SCr had a better
      sensitivity than first SCr for AKI (93% and 94% vs. 87%). Eighty-eight percent of
      patients experienced renal recovery at least 3 months after hospital discharge.
      All methods except the first SCr significantly underestimated the percentage of
      renal recovery. In a multivariate model, age, male gender, hypertension, heart
      failure, undergoing surgery and log first SCr best predicted preadmission SCr
      (adjusted R2 = 0.56). Imputation methods with first SCr increased AKI incidence
      to 23.9% (kappa = 0.92) but not with MDRD computed SCr (26.7%;kappa = 0.89).
      CONCLUSION: In our cohort, first SCr performed better for AKI diagnosis and
      staging, as well as for renal recovery after hospital discharge than MDRD, CKD
      EPI or minimal SCr. However, MDRD SCr and CKD-EPI SCr improved AKI diagnosis
      sensitivity. Imputation methods minimally increased agreement for AKI diagnosis.

PMID- 28454563
TI  - Setting-related influences on physical inactivity of older adults in residential
      care settings: a review.
AB  - BACKGROUND: Despite the detrimental effects of physical inactivity for older
      adults, especially aged residents of residential care settings may spend much
      time in inactive behavior. This may be partly due to their poorer physical
      condition; however, there may also be other, setting-related factors that
      influence the amount of inactivity. The aim of this review was to review setting
      related factors (including the social and physical environment) that may
      contribute to the amount of older adults' physical inactivity in a wide range of
      residential care settings (e.g., nursing homes, assisted care facilities).
      METHODS: Five databases were systematically searched for eligible studies, using
      the key words 'inactivity', 'care facilities', and 'older adults', including
      their synonyms and MeSH terms. Additional studies were selected from references
      used in articles included from the search. Based on specific eligibility
      criteria, a total of 12 studies were included. Quality of the included studies
      was assessed using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Based on
      studies using different methodologies (e.g., interviews and observations), and of
      different quality (assessed quality range: 25-100%), we report several aspects
      related to the physical environment and caregivers. Factors of the physical
      environment that may be related to physical inactivity included, among others,
      the environment's compatibility with the abilities of a resident, the presence of
      equipment, the accessibility, security, comfort, and aesthetics of the
      environment/corridors, and possibly the presence of some specific areas.
      Caregiver-related factors included staffing levels, the available time, and the
      amount and type of care being provided. CONCLUSIONS: Inactivity levels in
      residential care settings may be reduced by improving several features of the
      physical environment and with the help of caregivers. Intervention studies could
      be performed in order to gain more insight into causal effects of improving
      setting-related factors on physical inactivity of aged residents.

PMID- 28454564
TI  - Intravoxel incoherent motion DWI of the pancreatic adenocarcinomas:
      monoexponential and biexponential apparent diffusion parameters and
      histopathological correlations.
AB  - BACKGROUND: To investigate the associations between the diffusion parameters
      obtained from multiple-b-values diffusion weighted imaging (DWI) of pancreatic
      ductal adenocarcinoma (PDAC) and the aggressiveness and local stage prediction,
      and assess the values of the quantitative parameters for the discrimination of
      tumors from healthy pancreas. METHODS: Fifty-one patients with surgical pathology
      proven PDAC (size, 35 +/- 12 mm) and fifty-seven healthy volunteers were
      enrolled. Diffusion parameters including monoexponential apparent diffusion
      coefficient (ADCb and ADCtotal) and biexponential intravoxel incoherent motion
      (IVIM) parameters (ADCslow, ADCfast and f) based on 9 b-values (0 to 1000s/mm2)
      DWI were calculated for the lesions and the healthy pancreas. These parameters
      were compared by grades of differentiation, lymph node status, tumor stage and
      location. The diagnostic performances were calculated and compared by using the
      receiver operating characteristic curves (ROC) analyses. RESULTS: There was no
      statistically significant difference in ADCb, ADCtotal, ADCslow, ADCfast or f
      between PDAC stage T1/T2 and stage T3/T4 or moderately differentiated versus
      poorly differentiated PDAC (p = 0.060-0.941). In addition, no significant
      differences were observed for the quantitative parameters between tumors located
      in the pancreatic head versus other pancreatic regions (p = 0.203-0.954) or
      between tumors with and without metastatic peri-pancreatic lymph nodes (p = 0.313
      0.917). ADC25-600, ADC1000, ADCtotal and ADCfast were significantly lower for
      PDAC compared the healthy pancreas (all p < 0.05). ROC analyses showed the area
      under curve for ADC20 was the largest (0.911) to distinguish PDAC from normal
      pancreas (cut-off value, 5.58 * 10-3mm2/s) and had the highest combined
      sensitivity (89.5%) and specificity (82.4%). CONCLUSIONS: Multiple-b-values DWI
      derived monoexponential and biexponential parameters of PDAC do not exhibit
      significance dependence on tumor grade or tumor characteristics. ADC20 provided
      the best accuracy for differentiating PDAC from healthy pancreas in the study.

PMID- 28454565
TI  - Combined GWAS and 'guilt by association'-based prioritization analysis identifies
      functional candidate genes for body size in sheep.
AB  - BACKGROUND: Body size in sheep is an important indicator of productivity, growth
      and health as well as of environmental adaptation. It is a composite quantitative
      trait that has been studied with high-throughput genomic methods, i.e. genome
      wide association studies (GWAS) in various mammalian species. Several genomic
      markers have been associated with body size traits and genes have been identified
      as causative candidates in humans, dog and cattle. A limited number of related
      GWAS have been performed in various sheep breeds and have identified genomic
      regions and candidate genes that partly account for body size variability. Here,
      we conducted a GWAS in Frizarta dairy sheep with phenotypic data from 10 body
      size measurements and genotypic data (from Illumina ovineSNP50 BeadChip) for 459
      ewes. RESULTS: The 10 body size measurements were subjected to principal
      component analysis and three independent principal components (PC) were
      constructed, interpretable as width, height and length dimensions, respectively.
      The GWAS performed for each PC identified 11 significant SNPs, at the chromosome
      level, one on each of the chromosomes 3, 8, 9, 10, 11, 12, 19, 20, 23 and two on
      chromosome 25. Nine out of the 11 SNPs were located on previously identified
      quantitative trait loci for sheep meat, production or reproduction. One hundred
      and ninety-seven positional candidate genes within a 1-Mb distance from each
      significant SNP were found. A guilt-by-association-based (GBA) prioritization
      analysis (PA) was performed to identify the most plausible functional candidate
      genes. GBA-based PA identified 39 genes that were significantly associated with
      gene networks relevant to body size traits. Prioritized genes were identified in
      the vicinity of all significant SNPs except for those on chromosomes 10 and 12.
      The top five ranking genes were TP53, BMPR1A, PIK3R5, RPL26 and PRKDC.
      CONCLUSIONS: The results of this GWAS provide evidence for 39 causative candidate
      genes across nine chromosomal regions for body size traits, some of which are
      novel and some are previously identified candidates from other studies (e.g.
      TP53, NTN1 and ZNF521). GBA-based PA has proved to be a useful tool to identify
      genes with increased biological relevance but it is subjected to certain
      limitations.

PMID- 28454566
TI  - Apoptosis-induced effects of extract from Artemisia annua Linne by modulating
      PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116
      colon cancer cells.
AB  - BACKGROUND: The extracts from Artemisia annua Linne (AAE) has been known to
      possess various functions including anti-bacterial, anti-virus and anti-oxidant
      effects. However, the mechanism of those effects of AAE is not well known.
      Pursuantly, we determined the apoptotic effects of extract of AAE in HCT116 cell.
      In this study, we suggested that AAE may exert cancer cell apoptosis through
      PTEN/PDK1/Akt/p53signal pathway and mitochondria-mediated apoptotic proteins.
      METHODS: We measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay, lactate dehydrogenase (LDH) assay, Hoechst 33342 staining, Annexin V
      PI staining, Mitopotential assay, immunofluorescence (IF) and Western blotting.
      Accordingly, our study showed that AAE treatment to HCT116 cells resulted in
      inhibition of PDK1, Akt, MDM2, Bcl-2, and pro-caspase 3 as well as activation of
      PTEN, p53-upregulated modulator of apoptosis (PUMA), Bax and Bak expression. Also
      we measured in vivo assay that xenograft model, H&E assay, TUNEL assay and IHC.
      RESULTS: AAE induced apoptosis via PTEN/p53/PDK1/Akt signal pathways through
      PTEN/p53-independent manner. AAE inhibit cell viability and increase LDH release
      in HCT116 colon cancer cell. Also, AAE increase apoptotic bodies, caspase -3,7
      activation and reduces mitochondria membrane potential. AAE regulates cytochrome
      c translocation to the cytoplasm and Bax translocation to the mitochondrial
      membrane in an Immunofluorescence staining and increase PTEN and p53 expression
      in an in vivo tumor xenograft model. To elucidate the role of the
      PTEN/p53/PDK1/Akt signal pathways in cancer control, we conditionally inactivated
      PTEN/p53/PDK1/Akt signal pathways. We used inhibitors of PTEN, p53, PDK1, Akt. In
      consequence, these results indicate that AAE induced apoptosis by means of a
      mitochondrial event through the regulation of proteins such as Bax, Bak and
      cytochrome c in PDK1/Akt signaling pathways via PTEM/p53-independent manner.
      CONCLUSIONS: We confirmed the apoptotic effect of extracts of AAE by Modulating
      PTEN/p53/PDK1/Akt/Signal Pathways through PTEN/p53-independent pathwaysin HCT116
      colon cancer cell.

PMID- 28454567
TI  - Patterns and predictors of antimicrobial resistance among Staphylococcus spp.
      from canine clinical cases presented at a veterinary academic hospital in South
      Africa.
AB  - BACKGROUND: Antimicrobial resistance in staphylococci, often associated with
      treatment failure, is increasingly reported in veterinary medicine. The aim of
      this study was to investigate patterns and predictors of antimicrobial resistance
      among Staphylococcus spp. isolates from canine samples submitted to the
      bacteriology laboratory at the University of Pretoria academic veterinary
      hospital between 2007 and 2012. Retrospective data of 334 Staphylococcus isolates
      were used to calculate the proportion of samples resistant to 15 antimicrobial
      agents. The Cochran-Armitage trend test was used to investigate temporal trends
      and logistic regression models were used to investigate predictors of
      antimicrobial resistance in Staphylococcus aureus and Staphylococcus
      pseudintermedius. RESULTS: Results show that 98.2% (55/56) of the S. aureus
      isolates were resistant to at least one drug while 42.9% were multidrug
      resistant. Seventy-seven percent (214/278) of the S. pseudintermedius isolates
      were resistant to at least one drug and 25.9% (72/278) were multidrug resistant.
      Resistance to lincospectin was more common among S. aureus (64.3%) than S.
      pseudintermedius (38.9%). Similarly, resistance to clindamycin was higher in S.
      aureus (51.8%) than S. pseudintermedius (31.7%) isolates. There was a significant
      (p = 0.005) increase in S. aureus resistance to enrofloxacin over the study
      period. Similarly, S. pseudintermedius exhibited significant increasing temporal
      trend in resistance to trimethoprim-sulphamethoxazole (p = 0.004), clindamycin (p
      = 0.022) and orbifloxacin (p = 0.042). However, there was a significant
      decreasing temporal trend in the proportion of isolates resistant to doxycycline
      (p = 0.041), tylosin (p = 0.008), kanamycin (p = 0.017) and
      amoxicillin/clavulanic acid (p = 0.032). CONCLUSIONS: High levels of multidrug
      resistance and the increasing levels of resistance to sulphonamides, lincosamides
      and fluoroquinolones among Staphylococcus spp. isolates in this study are
      concerning. Future studies will need to investigate local drivers of
      antimicrobial resistance to better guide control efforts to address the problem.

PMID- 28454568
TI  - Double-adjustment in propensity score matching analysis: choosing a threshold for
      considering residual imbalance.
AB  - BACKGROUND: Double-adjustment can be used to remove confounding if imbalance
      exists after propensity score (PS) matching. However, it is not always possible
      to include all covariates in adjustment. We aimed to find the optimal imbalance
      threshold for entering covariates into regression. METHODS: We conducted a series
      of Monte Carlo simulations on virtual populations of 5,000 subjects. We performed
      PS 1:1 nearest-neighbor matching on each sample. We calculated standardized mean
      differences across groups to detect any remaining imbalance in the matched
      samples. We examined 25 thresholds (from 0.01 to 0.25, stepwise 0.01) for
      considering residual imbalance. The treatment effect was estimated using logistic
      regression that contained only those covariates considered to be unbalanced by
      these thresholds. RESULTS: We showed that regression adjustment could
      dramatically remove residual confounding bias when it included all of the
      covariates with a standardized difference greater than 0.10. The additional
      benefit was negligible when we also adjusted for covariates with less imbalance.
      We found that the mean squared error of the estimates was minimized under the
      same conditions. CONCLUSION: If covariate balance is not achieved, we recommend
      reiterating PS modeling until standardized differences below 0.10 are achieved on
      most covariates. In case of remaining imbalance, a double adjustment might be
      worth considering.

PMID- 28454570
TI  - Erratum to: Do the correlates of screen time and sedentary time differ in
      preschool children?

PMID- 28454569
TI  - Psychometric properties of the 10-item ruminative response scale in Chinese
      university students.
AB  - BACKGROUND: Rumination increases vulnerability to depression, exacerbates and
      perpetuates negative moods. This study was aimed to examine the psychometric
      properties of the Chinese version of the 10-item Ruminative Response Scale (RRS
      10) in a large undergraduate sample. METHODS: A sample of 5,236 university
      students finished the RRS and the Center for Epidemiological Studies Depression
      Scale (CES-D). Confirmatory Factor Analysis (CFA) was performed to examine the
      two-factor structure and the measurement equivalence of the RRS-10 across gender.
      The internal consistency, test-retest reliability, correlations among RRS, RRS-10
      and CES-D were also explored. In addition, gender difference on rumination and
      the relationship between rumination and depression were further investigated.
      RESULTS: The two-factor model of RRS-10 fit the data reasonably and had
      acceptable internal consistency and test-retest reliability in Chinese
      undergraduates sample. And the measurement equivalence of the RRS-10 was
      acceptable across gender in Chinese university students. Findings in respect of
      latent means and manifest means revealed non-significant gender difference in RRS
      10. Besides, participants with high-level rumination had more depressive symptoms
      than those with low-level rumination. CONCLUSIONS: The Chinese version of the RRS
      10 showed good psychometric properties and was measurement invariant across
      gender in undergraduates.

PMID- 28454571
TI  - A vicious cycle among cognitions and behaviors enhancing risk for eating
      disorders.
AB  - BACKGROUND: Establishing the sequence in which risk factors for eating disorders
      (ED) emerge would enable more effective ED prevention. Thus, in our study we
      investigated reciprocal and indirect associations between three cognitive and
      behavioral ED determinants (appearance orientation, appearance worries, and
      dieting) emphasized in the transdiagnostic model of ED. METHODS: Data were
      collected in a non-clinical group of adolescents at Time 1 (T1), and then 2
      months (Time 2, T2)    and 13-months later (Time 3, T3). Participants (N = 1260)
      aged 13-19 completed a questionnaire encompassing their nutrition behaviors,
      beliefs about appearance, health and well-being. Weight and height were measured
      objectively. RESULTS: Higher levels of appearance orientation (T1) were
      associated with higher levels of appearance worries (T2) which in turn predicted
      dieting (T3). Dieting (T1) predicted higher levels of appearance orientation (T2)
      which in turn predicted higher levels of appearance worries (T3). Higher levels
      of appearance worries (T1) were associated with higher levels of appearance
      orientation (T2) which in turn predicted dieting (T3). Also, higher levels of
      appearance worries (T1) were associated with dieting (T2), and higher levels of
      appearance orientation (T3). CONCLUSIONS: The three transdiagnostic model
      variables formed a vicious cycle. Therefore, higher levels of one of ED
      determinants (appearance orientation, appearance worries or dieting) increase the
      likelihood of the elevated levels of two other ED determinants at follow-ups and
      thus enhances the risk for ED.

PMID- 28454572
TI  - Invasive pulmonary mucormycosis: rare presentation with pulmonary eosinophilia.
AB  - BACKGROUND: Fungi can cause a variety of infectious diseases, including invasive
      mycosis and non-invasive mycosis, as well as allergic diseases. The different
      forms of mycosis usually have been described as mutually exclusive, independent
      entities, with few descriptions of overlapping cases. Here, we describe the first
      reported case of a patient with the complication of pulmonary eosinophilia in the
      course of invasive mucormycosis. CASE PRESENTATION: A 74-year-old Japanese man
      with asthma-COPD overlap underwent emergency surgery for a ruptured abdominal
      aortic aneurysm. The surgery was successful, but fever and worsening dyspnea
      appeared and continued from postoperative day (POD) 10. A complete blood count
      showed leukocytosis with neutrophilia and eosinophilia, and the chest X-ray
      showed consolidation of the left upper lung at POD 15. We suspected nosocomial
      pneumonia together with an exacerbation of the asthma-COPD overlap, and both
      antibiotics and bronchodilator therapy were initiated. However, the symptoms,
      eosinophilia and imaging findings deteriorated. We then performed a bronchoscopy,
      and bronchoalveolar lavage (BAL) fluid analysis revealed an increased percentage
      of eosinophils (82% of whole cells) as well as filamentous fungi. We first
      suspected that this was a case of allergic bronchopulmonary mycosis (ABPM) caused
      by Aspergillus infection and began corticosteroid therapy with an intravenous
      administration of voriconazole at POD 27. However, the fungal culture examination
      of the BAL fluid revealed mucormycetes, which were later identified as
      Cunninghamella bertholletiae by PCR and DNA sequencing. We then switched the
      antifungal agent to liposomal amphotericin B for the treatment of the pulmonary
      mucormycosis at POD 29. Despite replacing voriconazole with liposomal
      amphotericin B, the patient developed septic shock and died at POD 39. The
      autopsy revealed that filamentous fungi had invaded the lung, heart, thyroid
      glands, kidneys, and spleen, suggesting that disseminated mucormycosis had
      occurred. CONCLUSIONS: We describe the first reported case of pulmonary
      mucormycosis with pulmonary eosinophilia caused by Cunninghamella bertholletiae,
      which resulted in disseminated mucormycosis. Although it is a rather rare case,
      two important conclusions can be drawn: i) mycosis can simultaneously cause both
      invasive infection and a host allergic reaction, and ii) Cunninghamella
      bertholletiae rarely infects immunocompetent patients.

PMID- 28454573
TI  - Long-term results of early adjuvant concurrent chemoradiotherapy for high-risk,
      early stage uterine cervical cancer patients after radical hysterectomy.
AB  - BACKGROUND: The aim of the present study was to investigate the long-term
      survival outcomes and toxicities associated with our experienced early
      administration of adjuvant concurrent chemoradiotherapy (CCRT). METHODS: Ninety
      eight patients with pelvic lymph node metastasis, positive resection margin,
      and/or parametrial invasion who received adjuvant CCRT between 1995 and 2011 were
      analyzed retrospectively. The first cycle of platinum-based adjuvant chemotherapy
      was initiated within 2-3 weeks after surgery (median, 12 days) and continued
      every 4 weeks for a total of 4 cycles. Adjuvant radiotherapy was performed during
      the second and third cycles of chemotherapy. RESULTS: After a median follow-up
      period of 119 months for survivors, 13 patients (13.3%) experienced recurrence
      and 11 patients died of cancer during the follow-up period. The 5-year recurrence
      free survival and cancer specific survival rates were 87.6% and 90.6%,
      respectively. Ninety-four patients (95.9%) received >=3 cycles of chemotherapy.
      Total radiation dose of >=45 Gy was delivered in 91 patients (92.9%). Grade 3-4
      hematologic and gastrointestinal toxicities developed in 37 (37.8%) and 14
      (14.3%) patients during CCRT, respectively. CONCLUSION: The present study
      confirmed the long-term safety and encouraging survival outcomes of early
      administration of adjuvant CCRT, suggesting the benefits of early time to
      initiation of adjuvant treatments.

PMID- 28454574
TI  - Erratum to: Detection of a novel circovirus PCV3 in pigs with cardiac and multi
      systemic inflammation.

PMID- 28454575
TI  - Ziziphi spinosae lily powder suspension in the treatment of depression-like
      behaviors in rats.
AB  - BACKGROUND: Depression is a chronic, recurring and potentially life-threatening
      illness. Current treatments for depression are characterized by a low success
      rate and associated with a wide variety of side effects. The aim of the present
      study was to evaluate the behavioral anti-depressant effect of a novel herbal
      compounds named ziziphi spinosae lily powder suspension, as well as to
      investigate its potential mechanisms. METHODS: Except for body weight, depressive
      like behaviors were also evaluated using forced swimming test, sucrose
      consumption test and open field test. In order to investigate the underlying
      potential mechanisms, serum 5-HT and brain 5-HIAA were measured using ultrahigh
      performance liquid chromatography and high-performance liquid chromatography,
      respectively. RESULTS: Results showed that the herbal compounds ziziphi spinosae
      lily suspension could alleviate depressive symptoms in rat model of chronic
      depression. Biochemical analysis revealed that the herbal compounds elevated
      serum 5-HT and brain 5-HIAA. CONCLUSION: Ziziphi spinosae lily powder suspension
      could alleviate depressive behaviors in depression model animals. The underlying
      mechanisms may be related to the increase of serum 5-HT in peripheral blood and 5
      HIAA in brain. The study provides important mechanistic insights into the
      protective effect of the herbal compounds against chronic depressive disorder and
      suggests that the herbal compounds may be a potential pharmacological agent for
      treatment of major depressive disorder.

PMID- 28454576
TI  - A field trial of a fixed combination of permethrin and fipronil (Effitix(r)) for
      the treatment and prevention of flea infestation in dogs living with sheep.
AB  - BACKGROUND: A large number of fleas parasitize dogs living with sheep in Greece.
      The primary aim of this randomized, blinded, placebo-controlled trial was to
      examine the efficacy of a permethrin-fipronil combination (Effitix(r)) for the
      treatment and prevention of flea infestation in dogs living with sheep and the
      secondary aim was to examine the efficacy of this intervention on flea
      infestation, pruritus and skin lesions of the people in contact with these dogs.
      METHODS: Thirty dogs living with sheep and infested by at least 10 fleas and all
      80 sheep living on the same premises were randomly allocated into equal groups.
      Group A dogs were treated three times, every 4 weeks, with a spot-on containing
      54.5% permethrin and 6.1% fipronil, group A sheep were treated, on the same days,
      with a pour-on containing 1% deltamethrin, whereas group B dogs were sham-treated
      and group B sheep were placebo-treated. Flea counting was performed at the
      beginning of the trial (day 0) and after 14, 28, 56 and 84 days and the first
      five fleas from each animal were used for species identification. At the same
      time points, flea infestation, pruritus and skin lesions of the people in contact
      with the dogs were assessed. RESULTS: The percentage of dogs with zero flea
      counts was significantly higher in group A than in group B on days 14, 28, 56 and
      84 and flea counts were significantly lower in group A dogs than in group B dogs
      at the same time points. The percent efficacy of the permethrin-fipronil
      combination was higher than 78% (arithmetic means) or than 96% (geometric means)
      throughout the study. No adverse reactions were recorded. Between the two flea
      species found on dogs, Ctenocephalides canis was predominant over C. felis. Flea
      infected sheep were not found at the beginning or during the study and no
      significant changes in flea infestation, pruritus and skin lesions of the people
      in contact with the dogs were witnessed throughout the study. CONCLUSIONS: A spot
      on solution containing 54.5% permethrin and 6.1% fipronil is safe and effective
      for the treatment and prevention of C. canis and C. felis infestations in dogs
      living with sheep.

PMID- 28454577
TI  - The landscape of BRAF transcript and protein variants in human cancer.
AB  - BACKGROUND: The BRAF protein kinase is widely studied as a cancer driver and
      therapeutic target. However, the regulation of its expression is not completely
      understood. RESULTS: Taking advantage of the RNA-seq data of more than 4800
      patients belonging to 9 different cancer types, we show that BRAF mRNA exists as
      a pool of 3 isoforms (reference BRAF, BRAF-X1, and BRAF-X2) that differ in the
      last part of their coding sequences, as well as in the length (BRAF-ref: 76 nt;
      BRAF-X1 and BRAF-X2: up to 7 kb) and in the sequence of their 3'UTRs. The
      expression levels of BRAF-ref and BRAF-X1/X2 are inversely correlated, while the
      most prevalent among the three isoforms varies from cancer type to cancer type.
      In melanoma cells, the X1 isoform is expressed at the highest level in both
      therapy-naive cells and cells with acquired resistance to vemurafenib driven by
      BRAF gene amplification or expression of the Delta[3-10] splicing variant. In
      addition to the BRAF-ref protein, the BRAF-X1 protein (the full length as well as
      the Delta[3-10] variant) is also translated. The expression levels of the BRAF
      ref and BRAF-X1 proteins are similar, and together they account for BRAF
      functional activities. In contrast, the endogenous BRAF-X2 protein is hard to
      detect because the C-terminal domain is selectively recognized by the ubiquitin
      proteasome pathway and targeted for degradation. CONCLUSIONS: By shedding light
      on the repertoire of BRAF mRNA and protein variants, and on the complex
      regulation of their expression, our work paves the way to a deeper understanding
      of a crucially important player in human cancer and to a more informed
      development of new therapeutic strategies.

PMID- 28454578
TI  - Evaluating the variation in the projected benefit of community-wide mass
      treatment for schistosomiasis: Implications for future economic evaluations.
AB  - BACKGROUND: The majority of schistosomiasis control programmes focus on targeting
      school-aged children. Expanding the use of community-wide mass treatment to reach
      more adults is under consideration. However, it should be noted that this would
      require a further increase in programmatic resources, international aid, and
      commitment for the provision of praziquantel. Consequently, it is important to
      understand (i) where a change of strategy would have the greatest benefit, and
      (ii) how generalisable the conclusions of field trials and analytical studies
      based on mathematical models investigating the impact of community-wide mass
      treatment, are to a broad range of settings. METHODS: In this paper, we employ a
      previously described deterministic fully age-structured schistosomiasis
      transmission model and evaluate the benefit of community-wide mass treatment both
      in terms of controlling morbidity and eliminating transmission for Schistosoma
      mansoni, across a wide range of epidemiological settings and programmatic
      scenarios. This included variation in the baseline relative worm pre-control
      burden in adults, the overall level of transmission in defined settings, choice
      of effectiveness metric (basing morbidity calculations on prevalence or
      intensity), the level of school enrolment and treatment compliance. RESULTS:
      Community-wide mass treatment was found to be more effective for controlling the
      transmission of schistosome parasites than using a school-based programme only
      targeting school-aged children. However, in the context of morbidity control, the
      potential benefit of switching to community-wide mass treatment was highly
      variable across the different scenarios analysed. In contrast, for areas where
      the goal is to eliminate transmission, the projected benefit of community-wide
      mass treatment was more consistent. CONCLUSION: Whether community-wide mass
      treatment is appropriate will depend on the local epidemiological setting (i.e.
      the relative pre-control burden in adults and transmission intensity), and
      whether the goal is morbidity control or eliminating transmission. This has
      important implications regarding the generalisability of cost-effectiveness
      analyses of schistosomiasis interventions. Our results indicate that areas with
      poor school-enrolment/coverage could benefit more from community-wide treatment
      of praziquantel and should potentially be prioritised for any change in strategy.
      This work highlights the importance of not over-generalising conclusions and
      policy in this area, but of basing decisions on high quality epidemiological data
      and quantitative analyses of the impact of interventions in a range of settings.

PMID- 28454579
TI  - A retro-inverso cell-penetrating peptide for siRNA delivery.
AB  - BACKGROUND: Small interfering RNAs (siRNAs) are powerful tools to control gene
      expression. However, due to their poor cellular permeability and stability, their
      therapeutic development requires a specific delivery system. Among them, cell
      penetrating peptides (CPP) have been shown to transfer efficiently siRNA inside
      the cells. Recently we developed amphipathic peptides able to self-assemble with
      siRNAs as peptide-based nanoparticles and to transfect them into cells. However,
      despite the great potential of these drug delivery systems, most of them display
      a low resistance to proteases. RESULTS: Here, we report the development and
      characterization of a new CPP named RICK corresponding to the retro-inverso form
      of the CADY-K peptide. We show that RICK conserves the main biophysical features
      of its L-parental homologue and keeps the ability to associate with siRNA in
      stable peptide-based nanoparticles. Moreover the RICK:siRNA self-assembly
      prevents siRNA degradation and induces inhibition of gene expression.
      CONCLUSIONS: This new approach consists in a promising strategy for future in
      vivo application, especially for targeted anticancer treatment (e.g. knock-down
      of cell cycle proteins). Graphical abstract RICK-based nanoparticles: RICK
      peptides and siRNA self-assemble in peptide-based nanoparticles to penetrate into
      the cells and to induce target protein knock-down.

PMID- 28454581
TI  - Changing the culture of assessment: the dominance of the summative assessment
      paradigm.
AB  - BACKGROUND: Despite growing evidence of the benefits of including assessment for
      learning strategies within programmes of assessment, practical implementation of
      these approaches is often problematical. Organisational culture change is often
      hindered by personal and collective beliefs which encourage adherence to the
      existing organisational paradigm. We aimed to explore how these beliefs
      influenced proposals to redesign a summative assessment culture in order to
      improve students' use of assessment-related feedback. METHODS: Using the
      principles of participatory design, a mixed group comprising medical students,
      clinical teachers and senior faculty members was challenged to develop radical
      solutions to improve the use of post-assessment feedback. Follow-up interviews
      were conducted with individual members of the group to explore their personal
      beliefs about the proposed redesign. Data were analysed using a socio-cultural
      lens. RESULTS: Proposed changes were dominated by a shared belief in the primacy
      of the summative assessment paradigm, which prevented radical redesign solutions
      from being accepted by group members. Participants' prior assessment experiences
      strongly influenced proposals for change. As participants had largely only
      experienced a summative assessment culture, they found it difficult to
      conceptualise radical change in the assessment culture. Although all group
      members participated, students were less successful at persuading the group to
      adopt their ideas. Faculty members and clinical teachers often used indirect
      techniques to close down discussions. The strength of individual beliefs became
      more apparent in the follow-up interviews. CONCLUSIONS: Naive epistemologies and
      prior personal experiences were influential in the assessment redesign but were
      usually not expressed explicitly in a group setting, perhaps because of cultural
      conventions of politeness. In order to successfully implement a change in
      assessment culture, firmly-held intuitive beliefs about summative assessment will
      need to be clearly understood as a first step.

PMID- 28454580
TI  - Association of skewed X-chromosome inactivation with FMR1 CGG repeat length and
      anti-Mullerian hormone levels: a cohort study.
AB  - BACKGROUND: Premutation range CGGn repeats of the FMR1 gene denote risk toward
      primary ovarian insufficiency (POI), also called premature ovarian failure (POF).
      This prospective cohort study was undertaken to determine if X-chromosome
      inactivation skew (sXCI) is associated with variations in FMR1 CGG repeat length
      and, if so, is also associated with age adjusted antimullerian hormone (AMH)
      levels as an indicator of functional ovarian reserve (FOR). METHODS: DNA samples
      of 58 women were analyzed for methylation status and confirmation of CGGn repeat
      length. Based on previously described FMR1 genotypes, there were 18 women with
      norm FMR1 (both alleles in range of CGG n=26-34), and 40 women who had at least
      one allele at CGGn<26 or CGG>34 ( not-norm FMR1). As part of a routine evaluation
      of ovarian reserve, patients at our fertility center have their serum AMH
      assessed at first visit. Regression models were used to test the association of
      ovarian reserve, as indicated by serum AMH, with sXCI. RESULTS: sXCI was
      significantly lower among infertility patients with norm FMR1 (6.5 +/- 11.1,
      median and IQR) compared to those with not-norm FMR1 (12.0 +/- 14.6, P = 0.005),
      though among young oocyte donors the opposite effect was observed. Women age >30
      to 38 years old demonstrated greater ovarian reserve in the presence of lower
      sXCI as evidenced by significantly higher AMH levels (GLM sXCI_10%, f = 11.27; P
      = 0.004). CONCLUSIONS: Together these findings suggest that FMR1 CGG repeat
      length may have a role in determining X-chromosome inactivation which could
      represent a possible mechanism for previously observed association of low age
      adjusted ovarian reserve with FMR1 variations in repeat length. Further, larger,
      investigations will be required to test this hypothesis.

PMID- 28454582
TI  - Analysis of necroptotic proteins in failing human hearts.
AB  - BACKGROUND: Cell loss and subsequent deterioration of contractile function are
      hallmarks of chronic heart failure (HF). While apoptosis has been investigated as
      a participant in the progression of HF, it is unlikely that it accounts for the
      total amount of non-functional tissue. In addition, there is evidence for the
      presence of necrotic cardiomyocytes in HF. Therefore, the objective of this study
      was to investigate the necroptotic proteins regulating necroptosis, a form of
      programmed necrosis, and thereby assess its potential role in human end-stage HF.
      METHODS: Left ventricular samples of healthy controls (C) and patients with end
      stage HF due to myocardial infarction (CAD) or dilated cardiomyopathy (DCM) were
      studied. Immunoblotting for necroptotic and apoptotic markers was performed.
      Triton X-114 fractionated samples were analyzed to study differences in
      subcellular localization. RESULTS: Elevated expression of RIP1 (receptor
      interacting protein), pSer227-RIP3 and its total levels were observed in HF
      groups compared to controls. On the other hand, caspase-8 expression, a
      proapoptotic protease negatively regulating necroptosis, was downregulated
      suggesting activation of necroptosis signaling. Total mixed-lineage kinase domain
      like protein (MLKL) expression did not differ among the groups; however, active
      cytotoxic forms of MLKL were present in all HF samples while they were expressed
      at almost undetectable levels in controls. Interestingly, pThr357-MLKL unlike
      pSer358-MLKL, was higher in DCM than CAD. In HF, the subcellular localization of
      both RIP3 and pThr357-MLKL was consistent with activation of necroptosis
      signaling. Expression of main apoptotic markers has not indicated importance of
      apoptosis. CONCLUSIONS: This is the first evidence showing that human HF of CAD
      or DCM etiology is positive for markers of necroptosis which may be involved in
      the development of HF.

PMID- 28454584
TI  - Direct expression of active human tissue inhibitors of metalloproteinases by
      periplasmic secretion in Escherichia coli.
AB  - BACKGROUND: As regulators of multifunctional metalloproteinases including MMP,
      ADAM and ADAMTS families, tissue inhibitors of metalloproteinases (TIMPs) play a
      pivotal role in extracellular matrix remodeling, which is involved in a wide
      variety of physiological processes. Since abnormal metalloproteinase activities
      are related to numerous diseases such as arthritis, cancer, atherosclerosis, and
      neurological disorders, TIMPs and their engineered mutants hold therapeutic
      potential and thus have been extensively studied. Traditional productions of
      functional TIMPs and their N-terminal inhibitory domains (N-TIMPs) rely on costly
      and time-consuming insect and mammalian cell systems, or tedious and inefficient
      refolding from denatured inclusion bodies. The later process is also associated
      with heterogeneous products and batch-to-batch variation. RESULTS: In this study,
      we developed a simple approach to directly produce high yields of active TIMPs in
      the periplasmic space of Escherichia coli without refolding. Facilitated by
      disulfide isomerase (DsbC) co-expression in protease-deficient strain BL21 (DE3),
      N-TIMP-1/-2 and TIMP-2 which contain multiple disulfide bonds were produced
      without unwanted truncations. 0.2-1.4 mg purified monomeric TIMPs were typically
      yielded per liter of culture media. Periplasmically produced TIMPs exhibited
      expected inhibition potencies towards MMP-1/2/7/14, and were functional in
      competitive ELISA to elucidate the binding epitopes of MMP specific antibodies.
      In addition, prepared N-TIMPs were fully active in a cellular context, i.e.
      regulating cancer cell morphology and migration in 2D and 3D bioassays.
      CONCLUSION: Periplasmic expression in E. coli is an excellent strategy to
      recombinantly produce active TIMPs and N-TIMPs.

PMID- 28454585
TI  - Modulatory role of regulatory T cells in a murine model of severe equine asthma.
AB  - BACKGROUND: It is accepted that T regulatory cells (Treg) control different types
      of immune responses. In connection with this role, we have recently described an
      important increase in CD4+, CD25high, Foxp3+ lymphocytes in the airway system of
      horses coursing with an exacerbation of severe equine asthma (EA). To explore the
      potential role of this population in the resolution of EA inflammation, we used a
      murine experimental model in which airway neutrophilic inflammation, which is
      similar to that observed in EA, is induced in mice by continual exposure to
      Aspergillus fumigatus contaminated hay. This model has the advantage that in mice
      we may induce a reduction of the Treg population using low doses of
      cyclophosphamide (Cy). RESULTS: The results indicated that the percentage of Treg
      cells increased with allergen exposure, as in horses; and animals partially
      depleted of Treg cells by treatment with Cy showed increased airway inflammation,
      demonstrated by an increased percentage of neutrophils and specific
      immunoglobulins in bronchoalveolar lavage fluid (BALF). Furthermore, a
      histopathologic study of animals that were pretreated with Cy before antigenic
      challenge showed higher cellular infiltration in the lung and deeper remodeling
      changes in the bronchi, including epithelial and goblet cell hyperplasia as well
      as airway smooth muscle hypertrophy. CONCLUSION: In this murine model of EA, the
      reduced number and function of Treg induced by low doses of Cy, which directly
      correlates with increased airway inflammation and lung infiltration, indicates
      that Treg may play a major role in the regulation and resolution of EA.

PMID- 28454583
TI  - Lymphoma InterVEntion (LIVE) - patient-reported outcome feedback and a web-based
      self-management intervention for patients with lymphoma: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Patients with lymphoma are at risk of experiencing adverse physical
      and psychosocial problems from their cancer and its treatment. Regular screening
      of these symptoms by the use of patient-reported outcomes (PROs) could increase
      timely recognition and adequate symptom management. Moreover, self-management
      interventions intend to enhance knowledge and skills and empower patients to
      better manage their disease and related problems. The objective of the Lymphoma
      InterVEntion (LIVE) trial is to examine whether feedback to patients on their
      PROs and access to a web-based, self-management intervention named Living with
      lymphoma will increase self-management skills and satisfaction with information,
      and reduce psychological distress. METHODS/DESIGN: The LIVE randomised controlled
      trial consists of three arms: (1) standard care, (2) PRO feedback, and (3) PRO
      feedback and the Living with lymphoma intervention. Patients who have been
      diagnosed with Hodgkin lymphoma, non-Hodgkin lymphoma, including chronic
      lymphocytic leukaemia, as registered in the Netherlands Cancer Registry in
      various hospitals will be selected for participation. Patients are invited via
      their haemato-oncologist 6 to 15 months after diagnosis. The PRO feedback
      includes a graphical overview of patients' own symptom and functioning scores and
      an option to compare their scores with those of other patients with lymphoma and
      a normative population of the same age and sex. The Living with lymphoma
      intervention is based on cognitive behavioural therapy components and includes
      information, assignments, assessments, and videos. Changes in outcomes from
      baseline to 16 weeks, 12, and 24 months post intervention will be measured.
      Primary outcomes are self-management skills, satisfaction with information, and
      psychological distress. Secondary outcomes are health-related quality of life,
      illness perceptions, fatigue, and health care use. DISCUSSION/DESIGN: The results
      of the LIVE trial will provide novel insights into whether access to PRO feedback
      and the Living with lymphoma intervention will be effective in increasing self
      management skills and satisfaction with information, and reducing distress. The
      LIVE trial is embedded in a population-based registry, which provides a unique
      setting to ascertain information on response, uptake, and characteristics of
      patients with lymphoma in web-based intervention(s). When effective, PRO feedback
      and Living with lymphoma could serve as easily and widely accessible
      interventions for coping with lymphoma. TRIAL REGISTRATION: Netherlands Trial
      Register, identifier NTR5953 . Registered on 14 July 2016.

PMID- 28454586
TI  - n-Hexane intoxication in a Chinese medicine pharmaceutical plant: a case report.
AB  - BACKGROUND: n-Hexane is a well-known neurotoxicant. Polyneuropathy due to
      occupational n-hexane exposure has been reported worldwide, however, our case is
      the first report in the Chinese herb industry. CASE PRESENTATION: A 25-year-old
      Asian man experienced progressive weakness and numbness in his hands and feet
      after working as an operator in a Chinese medicine pharmaceutical plant for the
      manufacture of Chinese herbal pain relief patches for 10 months.
      Electrophysiological studies indicated a reduction in nerve conduction velocity,
      prolongation of distal latencies, mildly positive sharp waves, and reduced
      recruitment with polyphasic potentials, particularly at distal sites.
      Demyelination with axonal degeneration caused by occupational n-hexane exposure
      was strongly suspected. Through investigation of our patient's workplace, the
      ambient n-hexane concentration in air was found to considerably exceed the
      permissible exposure limit/time-weighted average for n-hexane in Taiwan. His
      symptoms were gradually relieved after 4 months of cessation of exposure to n
      hexane. He was then confirmed as a case of occupational n-hexane intoxication.
      Further effective control measures should be implemented as soon as possible to
      prevent exposure of workers to n-hexane. CONCLUSIONS: Despite a typical clinical
      presentation, his exposure at workplace was appropriately investigated. Chemical
      exposure in Chinese medicine pharmaceutical plants could be an emerging issue
      that may affect workers' health. The lack of knowledge and management of solvents
      could endanger the health of workers. This case has profound educational
      implications for occupational health and is worthy of further follow-up for
      improving hazards control.

PMID- 28454588
TI  - A case matched study examining the reliability of using ImPACT to assess effects
      of multiple concussions.
AB  - BACKGROUND: Approximately 3.8 million sport and recreational concussions occur
      per year, creating a need for accurate diagnosis and management of concussions.
      Researchers and clinicians are exploring the potential dose-response cumulative
      effects of concussive injuries using computerized neuropsychological exams,
      however, results have been mixed and/or contradictory. This study starts with a
      large adolescent population and applies strict inclusion criteria to examine how
      previous mild traumatic brain injuries affect symptom reports and neurocognitive
      performance on the Immediate Post-concussion Assessment and Cognitive Testing
      (ImPACT) computerized tool. METHODS: After applying exclusion criteria and case
      matching, 204 male and 99 female participants remained. These participants were
      grouped according to sex and the number of previous self-reported concussions and
      examined for overall differences on symptoms reported and scores obtained on the
      ImPACT neurocognitive battery composites. In an effort to further reduce
      confounding factors due to the varying group sizes, participants were then case
      matched on age, sex, and body mass index and analyzed for differences on symptoms
      reported and scores obtained on the ImPACT neurocognitive battery composites.
      RESULTS: Case matched analysis demonstrated males with concussions experience
      significantly higher rates of dizziness (p = .027, eta2 = .035), fogginess (p =
      .038, eta2 = .032), memory problems (p = .003, eta2 = .055), and concentration
      problems (p = .009, eta2 = .046) than males with no reported previous
      concussions. No significant effects were found for females, although females
      reporting two concussions demonstrated a slight trend for experiencing higher
      numbers of symptoms than females reporting no previous concussions. CONCLUSIONS:
      The results suggest that male adolescent athletes reporting multiple concussions
      have lingering concussive symptoms well after the last concussive event; however,
      these symptoms were found to be conflicting and better explained by complainer
      versus complacent attitudes in the population examined. Our results conflict with
      a significant portion of the current literature that uses relatively lenient
      inclusion and exclusion criteria, providing evidence of the importance of strict
      inclusion and exclusion criteria and examination of confounding factors when
      assessing the effects of concussions.

PMID- 28454587
TI  - Emerging therapies for breast cancer.
AB  - HER2 and CDK4/6 are undoubted two most important biological targets for breast
      cancer. Anti-HER2 treatments enhance objective response and progression-free
      survival/disease-free survival as well as overall survival. Three CDK4/6
      inhibitors consistently improve objective response and progression-free survival;
      however, overall survival data are waited. Optimization of chemotherapy and
      endocrine strategies remains an unmet need. Check point inhibitor-based
      immunotherapy combined with chemotherapy is a promising field, especially for
      triple-negative breast cancer.

PMID- 28454589
TI  - Prevalence and antimicrobial resistance profile of Staphylococcus in dairy farms,
      abattoir and humans in Addis Ababa, Ethiopia.
AB  - BACKGROUND: Staphylococcus species cause mastitis and wound infection in
      livestock and food poisoning in humans through ingestion of contaminated foods,
      including meat and dairy products. They are evolving pathogens in that they
      readily acquire drug resistance, and multiple drug-resistant (MDR) isolates are
      increasing in human and veterinary healthcare. Therefore, this study was
      conducted to evaluate the prevalence of Staphylococci and their drug resistance
      in dairy farms and abattoir settings of Addis Ababa. METHODS: In this cross
      sectional study, 193 samples of milk, meat, equipment and humans working in the
      dairy farms and abattoir were collected (dairy farms = 72 and abattoir sources =
      121). Staphylococcus isolation and identification at the species level was done
      according to ISO-6888-3 using biochemical characteristics. An antimicrobial
      susceptibility test was conducted for 43 of the isolates using 15 antimicrobial
      agents commonly used for humans and livestock by the Kirby Bauer disk diffusion
      method following CLSI guidelines. RESULTS: Staphylococcus organism were isolated
      from 92 (47.7%) of the total 193 samples, 50% in the dairy farms and 46.3% in the
      abattoir. The isolated species were S. aureus (n = 31; 16.1%), S. intermedius (n
      = 21; 10.9%), S. hyicus (n = 16; 8.3%), and coagulase negative Staphylococcus
      (CNS) (n = 24; 12.4%). Gentamycin was effective drug as all isolates (n = 43;
      100%) were susceptible to it and followed by kanamycin (n = 39; 90.7%). However,
      the majority of the isolates showed resistance to penicillin-G (95.3%), nalidixic
      acid (88.4%), cloxacillin (79.1%), vancomycin (65.1%) and cefoxitin (55.8%). Of
      the 15 S. aureus tested for drug susceptibility, 73.3% of them were
      phenotypically resistant to vancomycin (VRSA) and all of the 15 isolates showed
      multi-drug resistance (MDR) to >3 drugs. Also, all of the tested CNS (100%), S.
      hyicus (100%) and the majority of S. intermedius isolates (88.9%) developed MDR.
      CONCLUSION: Alarmingly, the Staphylococcus isolates circulating in the dairy
      farms and abattoir in the study area harbor MDR. High level of Staphylococcus
      species isolation from personnel and equipment besides food (meat and milk)
      samples in dairy farms and abattoir settings reveals that the hygiene practice in
      the dairy farm and abattoir is substandard. Prudent drug use and improved
      hygienic practice is recommended in the dairy farms and abattoir to safeguard the
      public from the risk of acquiring infections and MDR pathogenic Staphylococcus.

PMID- 28454592
TI  - Increasing HIV testing among hard-to-reach groups: examination of RAPID, a
      community-based testing service in Queensland, Australia.
AB  - BACKGROUND: The success of 'treatment as prevention' (TasP) to control HIV relies
      on the uptake of testing across priority population groups. Innovative strategies
      including; rapid HIV testing (RHT) in community and outreach settings, engaging
      peer service providers, and not requiring disclosure of sexual history have been
      designed to increase access. This paper reports on the implementation of 'RAPID',
      a community-based testing program in Queensland, Australia that employs these
      strategies to increase access to testing. METHODS: Service data, including client
      registration forms and a satisfaction survey from all clients attending RAPID
      between August 2014 and July 2015 were analysed. RESULTS: In 2014/2015 1,199
      people attended RAPID to receive a free HIV test. The majority were urban-based
      gay men. 17.1% were first-time testers and 20.1% of participants were not
      eligible to access Medicare, Australia's universal health care scheme.
      CONCLUSIONS: RAPID's evidence-based strategies appear to facilitate access to HIV
      testing, particularly among those who have never tested before; however the
      implications for the ongoing treatment and care of people ineligible for
      Medicare, who test positive to HIV warrants careful consideration.

PMID- 28454591
TI  - Lost in translation: returning germline genetic results in genome-scale cancer
      research.
AB  - BACKGROUND: The return of research results (RoR) remains a complex and well
      debated issue. Despite the debate, actual data related to the experience of
      giving individual results back, and the impact these results may have on clinical
      care and health outcomes, is sorely lacking. Through the work of the Australian
      Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to
      the patient where actionable research data were identified; and (2) report the
      clinical utilisation of individual results returned. Using this experience, we
      discuss barriers and opportunities associated with a comprehensive process of RoR
      in large-scale genomic research that may be useful for others developing their
      own policies. METHODS: We performed whole-genome (n = 184) and exome (n = 208)
      sequencing of matched tumour-normal DNA pairs from 392 patients with sporadic
      pancreatic cancer (PC) as part of the APGI. We identified pathogenic germline
      mutations in candidate genes (n = 130) with established predisposition to PC or
      medium-high penetrance genes with well-defined cancer associated syndromes or
      phenotypes. Variants from candidate genes were annotated and classified according
      to international guidelines. Variants were considered actionable if clinical
      utility was established, with regard to prevention, diagnosis, prognostication
      and/or therapy. RESULTS: A total of 48,904 germline variants were identified,
      with 2356 unique variants undergoing annotation and in silico classification.
      Twenty cases were deemed actionable and were returned via previously described
      RoR framework, representing an actionable finding rate of 5.1%. Overall, 1.78% of
      our cohort experienced clinical benefit from RoR. CONCLUSION: Returning research
      results within the context of large-scale genomics research is a labour
      intensive, highly variable, complex operation. Results that warrant action are
      not infrequent, but the prevalence of those who experience a clinical difference
      as a result of returning individual results is currently low.

PMID- 28454593
TI  - Disseminated hyaline ring granuloma in the omentum of a dog.
AB  - BACKGROUND: Hyaline ring granuloma (HRG) is an uncommon histopathologic finding
      of unsolved etiopathogenesis. According to the exogenous theory, HRG develops due
      to implantation of foreign material, most probably indigestible plant fragments.
      HRG is a comparatively rare condition in humans, mostly involving the oral cavity
      with very rare extraoral locations. CASE PRESENTATION: An 1-year-old mixed-breed
      dog in good condition was presented for routine ovariohysterectomy. Disseminated
      HGR were accidentally found in the omental adipose tissue during surgery.
      Histopathology revealed the presence of ring-like hyaline structures surrounded
      by granulomatous inflammation including foreign body-type multinucleated giant
      cells. The histochemical examinations indicated the exogenous plant origin of the
      foreign material. CONCLUSIONS: The lesions were similar to the findings in humans
      with HRG. The definitive diagnosis remains largely based on histopathological
      examination supported by special histochemical stains. To the best of our
      knowledge, this is the first case of hyaline ring granuloma reported in a non
      human species. Moreover, the omentum is an uncommon location for this condition.

PMID- 28454594
TI  - Longitudinal study of Plasmodium pathogens identifies new loci associated with
      artemisinin resistance.
AB  - A longitudinal analysis of malaria parasite genomes has revealed new markers that
      can be used in public health efforts to limit the spread of multidrug-resistant
      malaria.

PMID- 28454596
TI  - Opioids Cause Central and Complex Sleep Apnea in Humans and Reversal With
      Discontinuation: A Plea for Detoxification.
AB  - ABSTRACT: Central sleep apnea (CSA) and continuous positive airway pressure
      (CPAP) emergent CSA are common in patients for whom opioids have been prescribed
      for chronic pain management. It is not known if opioids are the potential cause
      of CSA. We report the case of a patient who underwent multiple full nights of
      polysomnography testing while on opioids, off opioids, and with various positive
      airway pressure devices. While on opioids, the patient had severe CSA that
      persisted during both CPAP and bilevel titration but was eliminated with adaptive
      servoventilation therapy. Some time later, opioid use was discontinued by the
      patient. Repeat polysomnography showed resolution of the sleep-disordered
      breathing. Later-while the patient was still off opioids-she had gained weight
      and become symptomatic; polysomnography showed obstructive sleep apnea without
      CSA. This time, therapy with CPAP showed elimination of sleep apnea without
      emergent CSA. These data collectively indicate that opioids were the cause of CSA
      as well as emergent CSA.

PMID- 28454595
TI  - Expenditure and financial burden for the diagnosis and treatment of colorectal
      cancer in China: a hospital-based, multicenter, cross-sectional survey.
AB  - BACKGROUND: The increasing prevalence of colorectal cancer (CRC) in China and the
      paucity of information about relevant expenditure highlight the necessity of
      better understanding the financial burden and effect of CRC diagnosis and
      treatment. We performed a survey to quantify the direct medical and non-medical
      expenditure as well as the resulting financial burden of CRC patients in China.
      METHODS: We conducted a multicenter, cross-sectional survey in 37 tertiary
      hospitals in 13 provinces across China between 2012 and 2014. Each enrolled
      patient was interviewed using a structured questionnaire. All expenditure data
      were inflated to the 2014 Chinese Yuan (CNY; 1 CNY = 0.163 USD). We quantified
      the overall expenditure and financial burden and by subgroup (hospital type, age
      at diagnosis, sex, education, occupation, insurance type, household income,
      clinical stage, pathologic type, and therapeutic regimen). We then performed
      generalized linear modeling to determine the factors associated with overall
      expenditure. RESULTS: A total of 2356 patients with a mean age of 57.4 years were
      included, 57.1% of whom were men; 13.9% of patients had stage I cancer; and the
      average previous-year household income was 54,525 CNY. The overall average direct
      expenditure per patient was estimated to be 67,408 CNY, and the expenditures for
      stage I, II, III, and IV disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and
      82,729 CNY, respectively. Non-medical expenditure accounted for 8.3% of the
      overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed
      patient was 32,649 CNY, which accounted for 59.9% of their previous-year
      household income and caused 75.0% of families to suffer an unmanageable financial
      burden. Univariate analysis showed that financial burden and overall expenditure
      differed in almost all subgroups (P < 0.05), except for sex. Multivariate
      analysis showed that patients who were treated in specialized hospitals and those
      who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely
      to spend more, whereas those with a lower household income and those who
      underwent surgery spent less (all P < 0.05). CONCLUSIONS: For patients in China,
      direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,
      and non-medical expenditure was non-ignorable. The financial burden varied among
      subgroups, especially among patients with different clinical stages of disease,
      which suggests that, in China, CRC screening might be cost-effective.

PMID- 28454590
TI  - Protective intraoperative ventilation with higher versus lower levels of positive
      end-expiratory pressure in obese patients (PROBESE): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Postoperative pulmonary complications (PPCs) increase the morbidity
      and mortality of surgery in obese patients. High levels of positive end
      expiratory pressure (PEEP) with lung recruitment maneuvers may improve
      intraoperative respiratory function, but they can also compromise hemodynamics,
      and the effects on PPCs are uncertain. We hypothesized that intraoperative
      mechanical ventilation using high PEEP with periodic recruitment maneuvers, as
      compared with low PEEP without recruitment maneuvers, prevents PPCs in obese
      patients. METHODS/DESIGN: The PRotective Ventilation with Higher versus Lower
      PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a
      multicenter, two-arm, international randomized controlled trial. In total, 2013
      obese patients with body mass index >=35 kg/m2 scheduled for at least 2 h of
      surgery under general anesthesia and at intermediate to high risk for PPCs will
      be included. Patients are ventilated intraoperatively with a low tidal volume of
      7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with
      lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment
      maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed
      composite of single adverse pulmonary events and represents the primary endpoint.
      DISCUSSION: To our knowledge, the PROBESE trial is the first multicenter,
      international randomized controlled trial to compare the effects of two different
      levels of intraoperative PEEP during protective low tidal volume ventilation on
      PPCs in obese patients. The results of the PROBESE trial will support
      anesthesiologists in their decision to choose a certain PEEP level during general
      anesthesia for surgery in obese patients in an attempt to prevent PPCs. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May
      2014; last updated 7 June 2016.

PMID- 28454597
TI  - Time Trends in the Family Physician Management of Insomnia: The Australian
      Experience (2000-2015).
AB  - STUDY OBJECTIVES: To evaluate changes in rates of family physician (FP)
      management of insomnia in Australia from 2000-2015. METHODS: The Bettering the
      Evaluation And Care of Health (BEACH) program is a nationally representative
      cross-sectional survey of 1,000 newly randomly sampled family physicians'
      activity in Australia per year, who each record details of 100 consecutive
      patient encounters. This provided records of approximately 100,000 encounters
      each year. We identified all encounters with patients older than 15 years where
      insomnia or difficulty sleeping was managed and assessed trends in these
      encounters from 2000-2015. RESULTS: There was no change in the management rate of
      insomnia from 2000-2007 (1.54 per 100 encounters [95% confidence interval [CI]:
      1.49-1.58]). This rate was lower from 2008-2015 (1.31 per 100 encounters [95% CI:
      1.27-1.35]). There was no change in FP management: pharmacotherapy was used in
      approximately 90% of encounters; nonpharmacological advice was given at
      approximately 20%; and onward referral at approximately 1% of encounters.
      Prescription of temazepam changed from 54.6 [95% CI: 51.4-57.9] per 100 insomnia
      problems in 2000-2001 to 43.6 [95% CI: 40.1-47.0] in 2014-2015, whereas zolpidem
      increased steadily from introduction in 2000 to 14.6 [95% CI: 12.2-17.1] per 100
      insomnia problems in 2006-2007, and then decreased to 7.3 [95% CI: 5.4-9.2] by
      2014-2015. CONCLUSIONS: Insomnia management frequency decreased after 2007 in
      conjunction with ecologically associated Australian media reporting of adverse
      effects linked to zolpidem use. Australian FPs remain reliant on pharmacotherapy
      for the management of insomnia.

PMID- 28454598
TI  - The Accuracy, Night-to-Night Variability, and Stability of Frontopolar Sleep
      Electroencephalography Biomarkers.
AB  - STUDY OBJECTIVES: To assess the validity of sleep architecture and sleep
      continuity biomarkers obtained from a portable, multichannel forehead
      electroencephalography (EEG) recorder. METHODS: Forty-seven subjects
      simultaneously underwent polysomnography (PSG) while wearing a multichannel
      frontopolar EEG recording device (Sleep Profiler). The PSG recordings
      independently staged by 5 registered polysomnographic technologists were compared
      for agreement with the autoscored sleep EEG before and after expert review. To
      assess the night-to-night variability and first night bias, 2 nights of self
      applied, in-home EEG recordings obtained from a clinical cohort of 63 patients
      were used (41% with a diagnosis of insomnia/depression, 35% with
      insomnia/obstructive sleep apnea, and 17.5% with all three). The between-night
      stability of abnormal sleep biomarkers was determined by comparing each night's
      data to normative reference values. RESULTS: The mean overall interscorer
      agreements between the 5 technologists were 75.9%, and the mean kappa score was
      0.70. After visual review, the mean kappa score between the autostaging and five
      raters was 0.67, and staging agreed with a majority of scorers in at least 80% of
      the epochs for all stages except stage N1. Sleep spindles, autonomic activation,
      and stage N3 exhibited the least between-night variability (P < .0001) and
      strongest between-night stability. Antihypertensive medications were found to
      have a significant effect on sleep quality biomarkers (P < .02). CONCLUSIONS: A
      strong agreement was observed between the automated sleep staging and human
      scored PSG. One night's recording appeared sufficient to characterize abnormal
      slow wave sleep, sleep spindle activity, and heart rate variability in patients,
      but a 2-night average improved the assessment of all other sleep biomarkers.
      COMMENTARY: Two commentaries on this article appear in this issue on pages 771
      and 773.

PMID- 28454599
TI  - A Turbulent Night.

PMID- 28454601
TI  - Tympanic Membrane Perforation as a Complication of Continuous Positive Airway
      Pressure.

PMID- 28454602
TI  - Advancing Treatment of Comorbid PTSD and OSA.

PMID- 28454600
TI  - Sleep and Breathing the First Night After Adenotonsillectomy in Obese Children
      With Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: There are few studies measuring postoperative respiratory
      complications in obese children with obstructive sleep apnea (OSA) undergoing
      adenotonsillectomy (AT). These complications are further compounded by
      perioperative medications. Our objective was to study obese children with OSA for
      their respiratory characteristics and sleep architecture on the night of AT.
      METHODS: This was a prospective study at a tertiary pediatric hospital between
      January 2009-February 2012. Twenty obese children between 8-17 years of age with
      OSA and adenotonsillar hypertrophy were recruited. Patients underwent baseline
      polysomnography (PSG) and AT with or without additional debulking procedures,
      followed by a second PSG on the night of surgery. Demographic and clinical
      variables, surgical details, perioperative anesthetics and analgesics, and PSG
      respiratory and sleep architecture parameters were recorded. Statistical tests
      included Pearson correlation coefficient for correlation between continuous
      variables and chi-square and Wilcoxon rank-sum tests for differences between
      groups. RESULTS: Baseline PSG showed OSA with mean obstructive apnea-hypopnea
      index (oAHI) 27.1 +/- 22.9, SpO2 nadir 80.1 +/- 7.9%, and sleep fragmentation
      arousal index 25.5 +/- 22.0. Postoperatively, 85% of patients had abnormal sleep
      studies similar to baseline, with postoperative oAHI 27.0 +/- 34.3 (P = .204),
      SpO2 nadir, 82.0 +/- 8.7% (P = .462), and arousal index, 24.3 +/- 24.0 (P =
      .295). Sleep architecture was abnormal after surgery, showing a significant
      decrease in REM sleep (P = .003), and a corresponding increase in N2 (P = .017).
      CONCLUSIONS: Obese children undergoing AT for OSA are at increased risk for
      residual OSA on the night of surgery. Special considerations should be taken for
      postoperative monitoring and treatment of these children. COMMENTARY: A
      commentary on this article appears in this issue on page 775.

PMID- 28454603
TI  - Adverse Effects of Hypnotic Medications.

PMID- 28454604
TI  - WITHDRAWN: A Position Statement.

PMID- 28454605
TI  - A chaperone surveillance system in plant circadian rhythms.
AB  - The circadian clock is an internal system that is synchronized by external
      stimuli, such as light and temperature, and influences various physiological and
      developmental processes in living organisms. In the model plant Arabidopsis,
      transcriptional, translational and post-translational processes are interlocked
      by feedback loops among morning- and eveningphased genes. In a post-translational
      loop, plant-specific singlegene encoded GIGANTEA (GI) stabilize the F-box protein
      ZEITLUPE (ZTL), driving the targeted-proteasomal degradation of TIMING OF CAB
      EXPRESSION 1 (TOC1) and PSEUDORESPONSE REGULATOR 5 (PRR5). Inherent to this, we
      demonstrate the novel biochemical function of GI as a chaperone and/or co
      chaperone of Heat-Shock Protein 90 (HSP90). GI prevents ZTL degradation as a
      chaperone and facilitates ZTL maturation together with HSP90/HSP70, enhancing ZTL
      activity in vitro and in planta. GI is known to be involved in a wide range of
      physiology and development as well as abiotic stress responses in plants, but it
      could also interact with diverse client proteins to increase protein maturation.
      Our results provide evidence that GI helps proteostasis of ZTL by acting as a
      chaperone and a co-chaperone of HSP90 for proper functioning of the Arabidopsis
      circadian clock. [BMB Reports 2017; 50(5): 235-236].

PMID- 28454607
TI  - An FCA-mediated epigenetic route towards thermal adaptation of autotrophic
      development in plants.
AB  - Plants are able to recognize even small changes in surrounding temperatures to
      optimize their growth and development. At warm temperatures, plants exhibit
      diverse architectural adjustments, including hypocotyl and petiole elongation,
      leaf hyponasty, and reduced stomatal density. However, it was previously unknown
      how such warm temperatures affected the early stages of seedling development. In
      our recent study, we demonstrated that the RNA-binding protein, FCA, is critical
      for sustaining chlorophyll biosynthesis during early seedling development, which
      is a prerequisite for autotrophic transition at warm temperatures. FCA plays a
      dual role in this thermal response. It inhibits the rapid degradation of
      protochlorophyllide oxidoreductases (PORs) that mediate chlorophyll biosynthesis.
      In addition, it induces the expression of POR genes at the chromatin level, which
      contributes to maintaining functional enzyme levels. Our findings provide
      molecular basis for the thermal adaptation of chlorophyll biosynthesis during the
      early stages of seedling development in nature. [BMB Reports 2017; 50(7): 343
      344].

PMID- 28454608
TI  - Embrace Action: Take Charge of Your Health.

PMID- 28454606
TI  - Therapeutic implication of autophagy in neurodegenerative diseases.
AB  - Autophagy, a catabolic process necessary for the maintenance of intracellular
      homeostasis, has recently been the focus of numerous human diseases and
      conditions, such as aging, cancer, development, immunity, longevity, and
      neurodegeneration. However, the continued presence of autophagy is essential for
      cell survival and dysfunctional autophagy is thought to speed up the progression
      of neurodegeneration. The actual molecular mechanism behind the progression of
      dysfunctional autophagy is not yet fully understood. Emerging evidence suggests
      that basal autophagy is necessary for the removal of misfolded, aggregated
      proteins and damaged cellular organelles through lysosomal mediated degradation.
      Physiologically, neurodegenerative disorders are related to the accumulation of
      amyloid beta peptide and alpha-synuclein protein aggregation, as seen in patients
      with Alzheimer's disease and Parkinson's disease, respectively. Even though
      autophagy could impact several facets of human biology and disease, it generally
      functions as a clearance for toxic proteins in the brain, which contributes novel
      insight into the pathophysiological understanding of neurodegenerative disorders.
      In particular, several studies demonstrate that natural compounds or small
      molecule autophagy enhancer stimuli are essential in the clearance of amyloid
      beta and alpha-synuclein deposits. Therefore, this review briefly deliberates on
      the recent implications of autophagy in neurodegenerative disorder control, and
      emphasizes the opportunities and potential therapeutic application of applied
      autophagy. [BMB Reports 2017; 50(7): 345-354].

PMID- 28454609
TI  - Examining the Significance of Infection Prevention Practices.

PMID- 28454610
TI  - Indwelling Urinary Catheters: A Pathway to Health Care-Associated Infections.
AB  - When a urinary catheter is not inserted using proper technique, becomes unclean,
      or remains in place for too long, microorganisms can travel through the catheter
      lumen or along the outside of the catheter and infect the bladder or kidneys,
      resulting in a catheter-associated urinary tract infection (CAUTI). Urinary tract
      infections resulting from catheter use are one of the most common health care
      associated infections. The insertion of a urinary catheter is considered to be
      routine care. Improving practices of placement and removal of urinary catheters
      requires education aimed at changing the habits of nurses and physicians.
      Clinicians should follow evidence-based guidelines, including using aseptic
      technique for site preparation and supplies and limiting use and duration of the
      placement of urinary catheters. Perioperative personnel need to be aware of the
      risks of catheterization and take steps to prevent CAUTIs. This article discusses
      CAUTIs, including causes and strategies for prevention.

PMID- 28454611
TI  - Inadvertent Perioperative Hypothermia: Current Nursing Knowledge.
AB  - Inadvertent perioperative hypothermia is estimated to affect 70% of surgical
      patients and is associated with adverse clinical outcomes, lengthened hospital
      stays, and increased costs. To better understand the current level of nursing
      knowledge on this subject since the release of the "Guideline for prevention of
      unplanned patient hypothermia," we conducted an e-mail survey of AORN members.
      The overall response rate was 6.5% (N = 324), and most responding nurses
      overestimated or underestimated the lower and upper limits for normothermia. When
      asked about the most common complications associated with hypothermia,
      respondents identified shivering (68.2%), surgical site infections (65.4%), and
      cardiac events (61.7%); only 44.8% and 33.6% identified blood loss and pressure
      injuries, respectively. These results indicate a need for ongoing interventions
      to increase awareness and promote best practices to prevent and manage
      inadvertent perioperative hypothermia.

PMID- 28454612
TI  - Postoperative Distress of Orthopedic Ambulatory Surgery Patients.
AB  - Patients who undergo orthopedic ambulatory surgery have reported high levels of
      symptom distress during recovery at home. Content analysis of this qualitative
      descriptive study identified techniques of symptom management that effectively
      reduce postoperative symptom distress after orthopedic ambulatory surgery and
      provided insight into facilitators and barriers to postsurgery self-management.
      Focus groups consisted of 19 patients and caregivers recruited from a university
      orthopedic surgery office. The authors identified the common themes as
      distressing symptoms and consequences of surgery, management of symptoms, and
      self-management facilitators and barriers. Participants in our study noted the
      lack of continuity of care after discharge and wanted to know the realities of
      symptoms and receive more detailed information from care providers on how to self
      manage symptoms. Nurses involved in the care of these patients should focus not
      only on short-term recovery, but on preparing patients to manage sustained
      recovery issues at home.

PMID- 28454613
TI  - Back to Basics: Sterile Technique.
AB  - Sterile technique is an essential patient safety principle that reduces the risk
      of microbial transmission to patients during surgery. The ability to establish
      and maintain a sterile environment is an important skill for all perioperative
      team members. Understanding the principles of sterile technique is crucial for
      anyone entering the perioperative environment. This Back to Basics article
      reviews sterile technique and the importance of all perioperative team members
      adhering to aseptic principles.

PMID- 28454615
TI  - Guideline Summary: Surgical Smoke Safety.

PMID- 28454614
TI  - Guideline Implementation: Surgical Smoke Safety.
AB  - Research conducted during the past four decades has demonstrated that surgical
      smoke generated from the use of energy-generating devices in surgery contains
      toxic and biohazardous substances that present risks to perioperative team
      members and patients. Despite the increase in information available, however,
      perioperative personnel continue to demonstrate a lack of knowledge of these
      hazards and lack of compliance with recommendations for evacuating smoke during
      surgical procedures. The new AORN "Guideline for surgical smoke safety" provides
      guidance on surgical smoke management. This article focuses on key points of the
      guideline to help perioperative personnel promote smoke-free work environments;
      evacuate surgical smoke; and develop education programs and competency
      verification tools, policies and procedures, and quality improvement initiatives
      related to controlling surgical smoke. Perioperative RNs should review the
      complete guideline for additional information and for guidance when writing and
      updating policies and procedures.

PMID- 28454616
TI  - Self-Care Promotes Safer Patient Care.

PMID- 28454617
TI  - Clinical Issues-May 2017.
AB  - Standardized room layouts for minimally invasive surgery in a hybrid OR Key
      words: room setup, equipment placement, no-fly zone, collision. Measuring fluids
      during minimally invasive surgery procedures Key words: fluid distention media,
      hyponatremia, isotonic solution, hypotonic solution. Magnetic resonance imaging
      safety zones Key words: MRI, safety, zones, screening. Robot-assisted surgery
      competencies Key words: robotics, credentialing, competency verification.

PMID- 28454618
TI  - Evidence appraisal of Sandini M, Mattavelli I, Nespoli L, Uggeri F, Gianotti L.
      Systematic review and meta-analysis of sutures coated with triclosan for the
      prevention of surgical site infection after elective colorectal surgery according
      to the PRISMA statement.: Medicine. 2016;95(35):e4057.
      doi:10.1097/MD.0000000000004057.

PMID- 28454619
TI  - Guideline at a Glance: Specimen Management.

PMID- 28454620
TI  - The Risks of Absent Interoperability: Medication-Induced Hemolysis in a Patient
      With a Known Allergy.

PMID- 28454621
TI  - It Is Time to Address the Crisis in the Pharmacotherapy of Posttraumatic Stress
      Disorder: A Consensus Statement of the PTSD Psychopharmacology Working Group.

PMID- 28454622
TI  - Basic research and applied science in forensic entomology.

PMID- 28454623
TI  - Effects of different storage and measuring methods on larval length values for
      the blow flies (Diptera: Calliphoridae) Lucilia sericata and Calliphora vicina.
AB  - : In forensic entomology, the methods of sampling, killing, and storing
      entomological samples can affect larval age estimation, and, hence, the
      estimation of the minimum post-mortem interval. In the existing manuals, there is
      a certain amount of heterogeneity regarding methods and the recommendations for
      best practice in forensic entomology are insufficiently validated. This study
      evaluated three different length-measurement methods for larval stages and
      examined the influence of different killing and storing methods on the larval
      length of two forensically important blow flies, Lucilia sericata and Calliphora
      vicina. The three different measuring methods were a) a ruler with a 0.1mm scale,
      b) a geometrical micrometer, and c) a computer-aided stereomicroscope. They were
      used to measure the length of L1-L3C. vicina larvae and detect no significant
      differences. This supports the view that a simple tool like a geometrical
      micrometer can produce reliable results in forensic entomology. Newly hatched
      larvae of L. sericata and C. vicina were killed with hot water (HW) and divided
      into two equal subsamples. Lengths of all larvae were measured immediately after
      killing, then every 24h until day 4, and once more after 7days of storage in
      >=70%-ethanol. L. sericata larvae only showed significant changes in length in
      the HW group stored at room temperature. After 4 and 7days of storage, these 24-h
      and 72-h-old larvae showed a significant decrease in length compared with those
      in a fridge at 6 degrees C. This decrease can, however, be considered a
      negligible natural variation without forensically relevant consequences for
      larval age estimation of L. sericata samples. For C. vicina, an increase in
      length was observed over time. This was significant only for younger larvae (24
      48h old) stored in 70%-ethanol. This variance in length can lead to a wrong
      estimation of age; however, only for larvae stored in 70%-ethanol, not for those
      stored in 96%-ethanol. NOVELTY STATEMENT: We examined the influence of different
      killing and storing methods on two forensically important blow flies, Lucilia
      sericata and Calliphora vicina. For the latter species we additionally were
      evaluating three different length measurement methods. The results of both
      experiments suggest that it is possible to kill and store fly larvae directly in
      (not hot) >=70%-ethanol. This simplifies the sampling and storing of fly evidence
      at the crime scene. We also compared the influence of three different measuring
      methods for estimating the length of L1-L3 C. vicina larvae by using a) a ruler
      with a 0,1mm scaling, b) a geometrical micrometer and c) a computer-aided
      stereomicroscope. No significant differences were detected, supporting the view,
      that a simple tool like a geometrical micrometer can produce reliable results.
      This study helps to simplify the sampling and evaluation of entomological
      evidence and to backup or questioning existing guidelines and best practice
      recommendations.

PMID- 28454625
TI  - Age estimation by chest plate radiographs in a Thai male population.
AB  - Costal cartilage ossification on chest plate radiographs is one of the useful
      methods in age estimation for adults. This study was performed in 136 remains
      yielding a regression formula for age estimation in Thai male population. Eight
      features on chest plate imaging were scored based on Garvin's method. Composite
      scores were calculated by summation of all scores and analyzed to generate the
      regression of age as: Age=16.664*e0.161 (composite score) with a 95% prediction
      interval. The predicted age intervals in all composite scores were overlapping
      except for score 0 and 7. It could be concluded that if all features are
      absent/present, the person is likely to be less/more than 29years old.

PMID- 28454624
TI  - The use of immunochromatographic rapid test for soft tissue remains
      identification in order to distinguish between human and non-human origin.
AB  - Clear identification of soft tissue remains as being of non-human origin may be
      visually difficult in some cases e.g. due to decomposition. Thus, an additional
      examination is required. The use of an immunochromatographic rapid tests (IRT)
      device can be an easy solution with the additional advantage to be used directly
      at the site of discovery. The use of these test devices for detecting human blood
      at crime scenes is a common method. However, the IRT is specific not only for
      blood but also for differentiation between human and non-human soft tissue
      remains. In the following this method is discussed and validated by means of two
      forensic cases and several samples of various animals.

PMID- 28454626
TI  - Combined recovery of biological and fibre traces.
AB  - We present a method in which DNA and fibre traces are jointly recovered by
      taping. The DNA traces are isolated by standard laboratory procedures. Fibre
      traces are isolated afterwards in order to improve efficiency. Two tests have
      been carried out to evaluate the suitability of the presented method. In the
      first test, possible changes in appearance of fibres due to the DNA isolation
      procedures are investigated. In the second test, the recovery of fibres from a
      contaminated surface and their possible loss due to the DNA isolation procedure
      are investigated. It is concluded that polyester fibres are hardly affected by
      the DNA isolation procedure. In contrast, a relatively large number of the
      investigated cotton fibres were altered. The observed differences do not indicate
      a structural damage to the fibre or the dyes, but rather the washing-out of some
      components. The observed changes may require that fibres from a known source are
      also exposed to the DNA isolation procedures to assess the induced changes, but
      do not prevent a meaningful comparison. The recovery of fibres is slightly lower
      than the routine procedures for fibre recovery. Therefore, it was decided to
      perform extra taping of the recipient in cases where fibre investigation is
      requested. During DNA-isolation, some of the fibres present are released from the
      tapes. These fibres are not lost however, as they can be found on the filter in
      the used DNA isolation vials.

PMID- 28454627
TI  - Implementation and assessment of a likelihood ratio approach for the evaluation
      of LA-ICP-MS evidence in forensic glass analysis.
AB  - For the comparative analysis of glass fragments, a method using Laser Ablation
      Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) is in use at the NFI,
      giving measurements of the concentration of 18 elements. An important question is
      how to evaluate the results as evidence that a glass sample originates from a
      known glass source or from an arbitrary different glass source. One approach is
      the use of matching criteria e.g. based on a t-test or overlap of confidence
      intervals. An important drawback of this method is the fact that the rarity of
      the glass composition is not taken into account. A similar match can have widely
      different evidential values. In addition the use of fixed matching criteria can
      give rise to a "fall off the cliff" effect. Small differences may result in a
      match or a non-match. In this work a likelihood ratio system is presented,
      largely based on the two-level model as proposed by Aitken and Lucy [1], and
      Aitken, Zadora and Lucy [2]. Results show that the output from the two-level
      model gives good discrimination between same and different source hypotheses, but
      a post-hoc calibration step is necessary to improve the accuracy of the
      likelihood ratios. Subsequently, the robustness and performance of the LR system
      are studied. Results indicate that the output of the LR system is robust to the
      sample properties of the dataset used for calibration. Furthermore, the empirical
      upper and lower bound method [3], designed to deal with extrapolation errors in
      the density models, results in minimum and maximum values of the LR outputted by
      the system of 3.1*10-3 and 3.4*104. Calibration of the system, as measured by
      empirical cross-entropy, shows good behavior over the complete prior range. Rates
      of misleading evidence are small: for same-source comparisons, 0.3% of LRs
      support a different-source hypothesis; for different-source comparisons, 0.2%
      supports a same-source hypothesis. The authors use the LR system in reporting of
      glass cases to support expert opinion in the interpretation of glass evidence for
      origin of source questions.

PMID- 28454628
TI  - Accessible biometrics: A frustrated total internal reflection approach to imaging
      fingerprints.
AB  - Fingerprints are widely used as a means of identifying persons of interest
      because of the highly individual nature of the spatial distribution and types of
      features (or minuta) found on the surface of a finger. This individuality has led
      to their wide application in the comparison of fingerprints found at crime scenes
      with those taken from known offenders and suspects in custody. However, despite
      recent advances in machine vision technology and image processing techniques,
      fingerprint evidence is still widely being collected using outdated practices
      involving ink and paper - a process that can be both time consuming and
      expensive. Reduction of forensic service budgets increasingly requires that
      evidence be gathered and processed more rapidly and efficiently. However, many of
      the existing digital fingerprint acquisition devices have proven too expensive to
      roll out on a large scale. As a result new, low-cost imaging technologies are
      required to increase the quality and throughput of the processing of fingerprint
      evidence. Here we describe an inexpensive approach to digital fingerprint
      acquisition that is based upon frustrated total internal reflection imaging. The
      quality and resolution of the images produced are shown to be as good as those
      currently acquired using ink and paper based methods. The same imaging technique
      is also shown to be capable of imaging powdered fingerprints that have been
      lifted from a crime scene using adhesive tape or gel lifters.

PMID- 28454629
TI  - Study of fingerprints in Argentina population for application in personal
      identification.
AB  - The fingerprints of the Buenos Aires and Chubut provinces in Argentina have been
      studied, with the aim of knowing and quantifying the variability of these
      features, which are used in the identification process. The data studied for this
      research was obtained from 330 individuals, of both sexes, from two Argentinian
      population samples (170 individuals from Buenos Aires and 160 from Chubut), which
      amounts to a total of 3300 fingerprints. The different types of minutiae were
      located, identified, and visually quantified in four areas on the fingerprint.
      Two perpendicular axes were drawn whose intersection was located in the center of
      fingerprint. In addition, a circle was defined on these quadrants whose radius
      cut fifteen ridges. This method divides the fingerprints into four quadrants with
      two sectors apiece. The results obtained for both populations were compared
      statistically with those published previously for an Argentinian population
      sample, which had been collected using the same methodology. Therefore, Argentina
      becomes the country with the most information in this matter. For both
      populations, the highest frequencies were of ridge endings, followed by
      bifurcations and convergences. In this study of minutiae, statistically
      significant differences were found between the area of the fingerprint (inside
      and outside the circle), males and females, and types of main pattern for both
      samples. However, although the results show common patterns in the distribution
      of minutiae, there are also significant differences between populations. This
      reveals a significant ancestral and frequency effect of the minutiae, which would
      indicate that the minutiae are more genetically dependent than has been suspected
      so far. Furthermore, the non-equiprobability found for the frequency of the types
      of minutiae indicates that the weight provided by these characteristics is not
      the same when applied in identification processes, whether used quantitatively
      (numerical standard) or qualitatively (holistic method).

PMID- 28454630
TI  - Towards a Bayesian evaluation of features in questioned handwritten signatures.
AB  - In this work, we propose the construction of a evaluative framework for
      supporting experts in questioned signature examinations. Through the use of
      Bayesian networks, we envision to quantify the probative value of well defined
      measurements performed on questioned signatures, in a way that is both formalised
      and part of a coherent approach to evaluation. At the current stage, our project
      is explorative, focusing on the broad range of aspects that relate to comparative
      signature examinations. The goal is to identify writing features which are both
      highly discriminant, and easy for forensic examiners to detect. We also seek for
      a balance between case-specific features and characteristics which can be
      measured in the vast majority of signatures. Care is also taken at preserving the
      interpretability at every step of the reasoning process. This paves the way for
      future work, which will aim at merging the different contributions to a single
      probabilistic measure of strength of evidence using Bayesian networks.

PMID- 28454631
TI  - Understanding forensic expert evaluative evidence: A study of the perception of
      verbal expressions of the strength of evidence.
AB  - Verbal expressions of evidential strength are routinely used when presenting
      forensic expert evaluative evidence. The degree to which these verbal expressions
      are interpreted uniformly among different individuals requires further empirical
      study. This study focussed on groups of individuals with different roles within
      the criminal justice system and individuals with varying degrees of expertise and
      knowledge. Three groups of individuals were identified: laypeople, legal
      professionals and those with some forensic or investigative knowledge. The
      participants in the study (n=230) were provided with a case summary to which a
      verbal expression of the strength of evidence was randomly assigned. Participants
      were subsequently invited to indicate their perception of the strength of the
      evidence on a scale that was provided. Generally, across the study groups, the
      trend was one of increased perceived strength of evidence as the intended
      strength of the verbal expression was increased, with some notable exceptions. In
      general, there was good concordance between the groups in the way the different
      expressions were perceived. It was found that participants performed poorly when
      it came to differentiating between expressions at the 'strong' end of the scale
      ('strong', 'very strong' and 'extremely strong'). The findings resonate with
      calls for validated and robust communication frameworks for evaluative opinions.
      Further empirical research in this area is warranted and that such research can
      represent an important contribution towards improving the communication and
      presentation of forensic evidence.

PMID- 28454632
TI  - Evaluating evidence in linked crimes with multiple offenders.
AB  - In de Zoete et al. (2015) a framework for the evaluation of evidence when an
      individual is a suspect of two separate offenses (based on Evett et al., 2006) is
      implemented using a Bayesian network. Here, we extend this to situations with
      multiple offenders. When we have multiple offenders, new questions arise: (1) Can
      we distinguish between the offenders, even if we do not know their identity? (2)
      Do we know that certain pieces of evidence originate from the same person? (3) Do
      we know the number of offenders? With the aid of a mock case example, we show
      that such subtle differences between situations can lead to substantially
      different conclusions in terms of posterior probabilities of a certain suspect
      being one of the offenders in a particular crime. We reach our conclusions by
      constructing appropriate Bayesian networks for each situation. Although we find
      it undesirable that Bayesian networks are demonstrated in court, they can be very
      helpful in guiding expert and legal reasoning, identifying pitfalls and assist in
      preventing them. Bayesian networks can be used as a tool to understand how the
      different pieces of evidence influence each others evidential value, and the
      probabilities of the hypotheses of interest.

PMID- 28454633
TI  - Effective Cardiac Index and Systemic-Pulmonary Collaterals Evaluated by Cardiac
      Magnetic Resonance Late After Fontan Palliation.
AB  - The regulation of cardiac output in the Fontan circuit is not completely
      understood. Systemic-pulmonary collaterals (SPCs) are frequent in patients with
      univentricular heart, and their clinical significance and management remain
      controversial. The aims of our study were to identify factors associated with
      SPCs' flow at late follow-up after Fontan and evaluate the relation between SPCs
      flow (QSPCs) and the effective cardiac index (CI). From our cardiac magnetic
      resonance database, we identified all Fontan patients with a complete set of flow
      measurements allowing calculation of QSPCs and effective CI. QSPCs was calculated
      as (left pulmonary veins flow + right pulmonary veins flow) - (right pulmonary
      artery flow + left pulmonary artery flow). Effective CI was calculated as (Aortic
      flow (QAo) - QSPCs)/BSA. Medical, surgical history, and clinical status were
      recorded. Sixty-four post-Fontan patients (36 male; mean age 19 +/- 10 years)
      were included in the study. Median QSPCs was 0.7 L/min/m2 (interquartile [IQ]
      range 0.386-0.983) accounting for a median of 21% (IQ range 13-28) of aortic
      flow. The effective CI in our population was 2.4 +/- 0.6 L/min/m2. QSPCs
      inversely correlate with left pulmonary artery area (r = -0.37, p = 0.004) and
      total antegrade pulmonary flow (r = -0.32, p = 0.01). QSPCs correlate with
      indexed aortic flow (r = 0.6, p <0.001) and inversely correlate with effective CI
      (r = -0.39, p = 0.002). Effective CI inversely correlates with age at study and
      age at the Fontan palliation (r = -0.35, p = 0.005, and r = -0.29, p = 0.02,
      respectively) and positively with ventricular ejection fraction (r = 0.3, p =
      0.01). In conclusion, SPCs are common in Fontan patients, correlate inversely
      with effective CI, and are associated with a reduced antegrade pulmonary flow. In
      cardiac magnetic resonance evaluation of post-Fontan patients, effective CI
      should be taken into account rather than the total CI.

PMID- 28454634
TI  - Vibrations Generated by Several Nickel-titanium Endodontic File Systems during
      Canal Shaping in an Ex Vivo Model.
AB  - INTRODUCTION: This study aimed to compare the vibration generated by several
      nickel-titanium (NiTi) file systems and transmitted to teeth under 2 different
      motions (continuous rotation motion and reciprocating motion). METHODS: Sixty J
      shaped resin blocks (Endo Training Bloc-J; Dentsply Maillefer, Ballaigues,
      Switzerland) were trimmed to a root-shaped form and divided into 2 groups
      according to the types of electric motors: WaveOne motor (WOM, Dentsply
      Maillefer) and X-Smart Plus motor (XSM, Dentsply Maillefer). Each group was
      further subdivided into 3 subgroups (n = 10 each) according to the designated
      file systems: ProTaper Next (PTN, Dentsply Maillefer), ProTaper Universal (PTU,
      Dentsply Maillefer), and WaveOne (WOP, Dentsply Maillefer) systems. Vibration was
      measured during the pecking motion using an accelerometer attached to a
      predetermined consistent position. The average vibration values were subjected to
      2-way analysis of variance as well as the t test and Duncan test for post hoc
      comparison at the 95% confidence interval. RESULTS: Both motor types and
      instrument types produced significantly different ranges of average vibrations.
      Regardless of the instrument types, the WOM group generated greater vibration
      than the XSM group (P < .05). Although PTN and PTU did not show significant
      differences, the WOP group showed significantly greater vibration than the other
      groups regardless of motor types (P < .05). CONCLUSIONS: Under the limitations of
      this study design, the reciprocating NiTi file system may generate greater
      vibration than the continuous rotation NiTi file systems. The motor type also has
      a significant effect to amplify the vibrations.

PMID- 28454635
TI  - Corrigendum to "Protective effects of maslinic acid against alcohol-induced acute
      liver injury in mice" [Food and Chem. Toxicol. 74 (2014 Dec) 149-55].

PMID- 28454636
TI  - Carotid artery disease and perioperative stroke risk after surgical aortic valve
      replacement: A nationwide inpatient sample analysis.
AB  - To study the role of carotid stenosis (CS) and cerebrovascular disease as
      independent risk factors for perioperative stroke following surgical aortic valve
      replacement (SAVR). The National Inpatient Sample (NIS) database was used for our
      study. All patients who underwent SAVR from 1999 to 2011 were identified using
      ICD-9 codes. Univariate and multivariate analysis of baseline characteristics,
      Elixhauser comorbidities and other covariates were examined to identify
      independent predictors of perioperative strokes following SAVR. Data on 50,979
      patients who underwent SAVR from 1999 to 2011 was obtained. The mean age of the
      study cohort was 60.5. The study patients were predominantly Caucasian (79.3%)
      and males (60.01%). The incidence of perioperative stroke was 2.48%. CS (OR 1.8,
      95%CI 1.1-2.8, p=0.009) and cerebral arterial occlusion (OR 3.4, 95% CI 1.3-8.9)
      significantly increased perioperative stroke risk following SAVR. Infective
      endocarditis (OR 4.6, 95%CI 3.8-5.6, p=0.00) and neurological disorders (OR 4.8,
      95% CI 4-5.8, p=0.00) appeared to be the strongest risk factors for strokes.
      Other risk factors found to be significant predictors of perioperative strokes
      (p<0.05) were - age, higher VWR scores, CS, cerebral arterial occlusion,
      infective endocarditis, DM, HTN, renal failure, neurological disorders,
      coagulopathy and hypothyroidsm. In conclusion, perioperative stroke risk has
      remained more or less constant despite advancements in surgical techniques with
      risk having gone up in patients <65years of age. CS and cerebral arterial
      occlusion significantly increase stroke risk following SAVR. Improved patient
      selection with pre-operative risk stratification and institution of preventive
      strategies are necessary to improve operative outcomes following SAVR.

PMID- 28454637
TI  - Uptake and translocation of imidacloprid, thiamethoxam and difenoconazole in rice
      plants.
AB  - Uptake and translocation of imidacloprid (IMI), thiamethoxam (THX) and
      difenoconazole (DFZ) in rice plants (Oryza sativa L.) were investigated with a
      soil-treated experiment at two application rates: field rate (FR) and 10*FR under
      laboratory conditions. The dissipation of the three compounds in soil followed
      the first-order kinetics and DFZ showed greater half-lives than IMI and THX.
      Detection of the three compounds in rice tissues indicated that rice plants could
      take up and accumulate these pesticides. The concentrations of IMI and THX
      detected in leaves (IMI, 10.0 and 410 mg/kg dw; THX, 23.0 and 265 mg/kg dw) were
      much greater than those in roots (IMI, 1.37 and 69.3 mg/kg dw; THX, 3.19 and 30.6
      mg/kg dw), which differed from DFZ. The DFZ concentrations in roots (15.6 and
      79.1 mg/kg dw) were much greater than those in leaves (0.23 and 3.4 mg/kg dw).
      The bioconcentration factor (BCF), representing the capability of rice to
      accumulate contaminants from soil into plant tissues, ranged from 1.9 to 224.3
      for IMI, from 2.0 to 72.3 for THX, and from 0.4 to 3.2 for DFZ at different
      treated concentrations. Much higher BCFs were found for IMI and THX at 10*FR
      treatment than those at FR treatment, however, the BCFs of DFZ at both treatments
      were similar. The translocation factors (TFs), evaluating the capability of rice
      to translocate contaminants from the roots to the aboveground parts, ranged from
      0.02 to 0.2 for stems and from 0.02 to 9.0 for leaves. The tested compounds were
      poorly translocated from roots to stems, with a TF below 1. However, IMI and THX
      were well translocated from roots to leaves. Clothianidin (CLO), the main
      metabolite of THX, was detected at the concentrations from 0.02 to 0.5 mg kg-1 in
      soil and from 0.07 to 7.0 mg kg-1 in plants. Concentrations of CLO in leaves were
      almost 14 times greater than those in roots at 10*FR treatment.

PMID- 28454638
TI  - Foreword.

PMID- 28454639
TI  - Shorter Door-To-Balloon ST-Elevation Myocardial Infarction Time: Should There Be
      a Minimum Limit?
AB  - In ST-elevation myocardial infarction (STEMI) ischemic time is directly related
      to permanent myocardial damage and mortality. Therefore, it is crucial to restore
      myocardial perfusion rapidly. Door-to-balloon (DTB) time is defined as the
      duration between the arrival time of the patient to the medical facility until
      the time he or she is treated with percutaneous coronary intervention. Currently,
      DTB is the criterion that measures the quality of care provided to patients with
      STEMI at any given institution. It is well documented in the literature that
      longer DTB is associated with higher mortality; however, lowering DTB beyond
      current recommendations has not shown to decrease mortality rates. The current
      recommendations call for a DTB less than 90 minutes from the patient's first
      contact within the healthcare system, typically the arrival to the emergency
      department, to the time of the balloon inflation of the culprit coronary artery.
      Conversely, efforts to keep reducing DTB time may lead to unnecessary
      percutaneous coronary intervention (in false-positive STEMI) and delay
      appropriate therapy when needed, possibly missing an alternate potentially life
      threatening diagnosis. In conclusion, we herein review the literature on DTB and
      mortality rate. We also make suggestions about ideal DTB time and hazards of
      shortening it beyond the recommended guidelines.

PMID- 28454641
TI  - Design of PIlambdaDMU controller for global power control of Pressurized Heavy
      Water Reactor.
AB  - In this paper, a robust stabilizing controller design method is presented for
      global power control of a Pressurized Heavy Water Reactor (PHWR) under step-back
      condition scheme using a Fractional Order Proportional Integral Derivative
      (PIlambdaDMU) controller resulting into robust performance. The method is
      applicable to design a controller for One Non Integer Order Plus Time Delay
      (NIOPTD-I) plant which satisfies design specifications such as phase margin and
      gain crossover frequency. Stability boundary locus method is used in (Kp, Ki, Kd)
      parameter space for NIOPTD-I plants to obtain stability region. The robust
      performance is obtained by satisfying flat phase condition at gain crossover
      frequency where phase is almost constant for large span of frequencies. The
      simulation result of the proposed PIlambdaDMU controller shows active step-back
      control to the insertion of the rod with no undershoot and with the robust
      performance, hence safe to the plant for gain variations from 500% lower side to
      1000% upper side. The PIlambdaDMU controller with a plant shows that 30% and 50%
      global power drop from initial 100% is achieved in a reasonable time without
      undershoot.

PMID- 28454640
TI  - The advantage of digital tomosynthesis for pulmonary nodule detection concerning
      influence of nodule location and size: a phantom study.
AB  - AIM: To investigate the advantage of digital tomosynthesis (DTS) over chest
      radiography (CXR) and dual-energy subtraction radiography (DES) for pulmonary
      nodule detection according to the location and size of solid simulated pulmonary
      nodules (SPNs). MATERIALS AND METHODS: Ninety-six SPNs of variable sizes were
      inserted into eight different regions of a lung phantom. These regions were
      further classified into two groups of danger and non-danger zones based on
      anatomical location influencing the detection of pulmonary nodules. The 96 cases
      with inserted SPNs and an additional nodule-free 96 control cases all underwent
      CXR, DES, and DTS examinations. Three observers independently reviewed all the
      images. The jackknife alternative free-response receiver operating characteristic
      was used to analyse diagnostic performance for each technique. RESULTS: DTS was
      superior to CXR and DES for detection of smaller SPNs, except in the
      retrodiaphragmatic and apical regions. DTS outperformed CXR and DES for detection
      of larger SPNs in the paramediastinal region. For 5- and 8-mm SPNs, DTS was
      superior to CXR and DES in the apical, paramediastinal and lateral pulmonary
      regions. In the retrodiaphragmatic region, the three techniques showed similar
      diagnostic performance regardless of the SPN size. DES was similar to DTS for
      detection of 8-mm SPN in the apical region. For 10- and 12-mm SPNs, CXR and DES
      showed similar diagnostic performance to DTS in the apical and lateral pulmonary
      regions; however, DTS was superior to CXR and DES in the paramediastinal region.
      CONCLUSIONS: DTS significantly improved the capability to detect synthetic
      pulmonary nodules compared with CXR and DES, for detection of smaller nodules in
      the apical, paramediastinal, and lateral pulmonary regions, and larger nodules
      located in the paramediastinal region in a thoracic phantom.

PMID- 28454642
TI  - New results on Hinfinity filtering for Markov jump systems with uncertain
      transition rates.
AB  - In this paper, we study the Hinfinity filtering problem for a class of continuous
      time Markov jump systems with time-varying uncertainties in transition rates, in
      which the uncertain transition rates are assumed to be affine parameter-dependent
      uncertainty models. By converting the affine parameter-dependent uncertainty
      models for transition rates into time-varying polytopic ones and using the
      Lyapunov function approach, a sufficient condition on the existence of an
      Hinfinity filter is obtained in terms of a parameter-dependent matrix inequality.
      Also, the parameter-dependent matrix inequality is converted into a set of
      parameter-free linear matrix inequalities which can be solved numerically.
      Illustrative examples are given to demonstrate the effectiveness and advantages
      of the approach.

PMID- 28454643
TI  - The application of fractional order control for an air-based contactless
      actuation system.
AB  - Industry pushes towards ever faster and more accurate production of thin
      substrates. Contactless positioning offers advantages, especially in terms of
      risk of breakage and contamination. A system is considered designed for
      contactless positioning by floating a silicon wafer on a thin film of air. This
      paper focuses on the design of a control system, including actuators, sensors and
      control method, suitable for this purpose. Two cascaded control loops, with
      decoupled SISO controllers, are implemented for this moving mass controlled on a
      mass-spring system, which can be modelled as a fourth order system. The SISO
      controllers are first designed with classic loopshaping tools, which are then
      modified using fractional control. Two arguments based on examples in this system
      are given for the application of fractional control. Firstly, to increase the
      bandwidth of a regular mass-spring system, and secondly to control a plant which
      behaves fundamentally fractional, such as the moving mass in this cascaded fourth
      order system. By merely the application of fractionality, the bandwidths are
      extended by 14.6 % and 62 %, for the inner and outer loop respectively. A closed
      loop positioning bandwidth of the wafer of 60Hz is achieved, resulting in a
      positioning error of 104nm (2sigma value), which is limited by sensor noise and
      pressure disturbances. This paper shows how the extension of classic loopshaping
      tools with fractional control can directly improve the performance, without
      adding to the complicatedness of the control system. Moreover it demonstrates a
      working concept of a novel type of contactless actuator.

PMID- 28454644
TI  - Genetic diversity of immune-related antigens in Region of Difference 2 of
      Mycobacterium tuberculosis strains.
AB  - Region of Difference 2 (RD2) was lost during the ongoing propagation of BCG
      between 1927 and 1931, a time that coincides with reports of the ongoing
      attenuation of the vaccine. Some data demonstrate that RD2 plays a role in
      mycobacterial virulence, and that its deletion from Mycobacterium tuberculosis
      leads to a decrease in bacterial growth in both a macrophage and a murine model.
      Human T-cell epitopes of M. tuberculosis are evolutionarily hyperconserved and
      thus it was deduced that M. tuberculosis lacks antigenic variation and immune
      evasion. However, two antigens, Rv1986 and MPT64, encoded by RD2 harbored more
      than one amino acid changes. In this study, we used same set of clinical M.
      tuberculosis complex (MTBC) isolates from China, amplified the five genes
      containing T and B cell epitopes other than MPT64 encoded by RD2, and compared
      the sequences. It turned out that proteins in RD2 region, especially Rv1980c,
      Rv1985 and Rv1986 may be a special region that undergo antigenic variation in
      response to host immune pressure and may be involved in ongoing immune evasion.
      The dN/dS value of all six genes (including MPT64) were 2.33, much higher than 1,
      which means T cell antigens in RD2 region appeared to be under diversifying
      selection. Our data support the view that RD2 regions tend to be more variable
      than we expected to evade host immunity and the immune-related antigens in RD2
      were more variable than we expected, especially in T-cell epitope regions.

PMID- 28454645
TI  - Revisiting the Hunter Gaston discriminatory index: Note of caution and courses of
      change.
AB  - Hunter Gaston Discriminatory Index (HGDI) is a widely used estimator of
      discriminatory power of genotyping methods and diversity of molecular markers in
      bacterial pathogens, including Mycobacterium tuberculosis. In my opinion, the
      index is somewhat misleading: a closer look at common practice and particular
      studies reveals that values in the range of 0.6-0.9 are modest but uncritically
      perceived as high. I propose and discuss three courses of change: (i) to continue
      using HGDI but be aware of the true meaning behind its value and increase a
      threshold of acceptable resolution to the more adequate values of 0.90-0.99,
      depending on study design; (ii) to turn to other known indices of diversity
      (e.g., Shannon index), in order to complement HGDI; (iii) to develop new,
      intuitively more realistic estimator.

PMID- 28454646
TI  - Activity of rifampicin and linezolid combination in Mycobacterium tuberculosis.
AB  - BACKGROUND: Linezolid (LZD) is not commonly used for treating tuberculosis (TB),
      but in some patients with drug-resistant TB it is being used. However, the in
      vitro LZD activity, in combination with rifampicin (RIF) against Mycobacterium
      tuberculosis has not been fully elucidated. AIMS: The aim of this study was to
      evaluate the in vitro activity of RIF/LZD combination against M. tuberculosis
      clinical isolates. MATERIALS AND METHODS: The activity of the RIF/LZD combination
      was firstly determined in M. tuberculosis H37Rv, 14 susceptible, 9 isoniazid
      nonresistant and 14 multi-drug resistant (MDR) M. tuberculosis clinical isolates
      by modified checkerboard assay, Resazurin Drugs Combination Microtiter Assay
      (REDCA). After, the Time Kill Curve Assay, at 0.5 * MIC of drugs, in combination
      and alone, was performed in M. tuberculosis H37Rv and 8 (20.5%) of those clinical
      isolates, which the RIF/LZD combination showed to have synergistic effect by the
      checkerboard assay. RESULTS AND CONCLUSION: By Time Kill Curve Assay, we could
      observe in M. tuberculosis H37Rv and susceptible isolates, that LZD alone, at sub
      inhibitory concentration, has poor effect on the bacillus death. In some cases,
      the bacillus growth stayed constant while in others showed regrowth at the eighth
      day of drug exposure. RIF alone exhibits potent concentration-dependent
      bactericidal activity, and was strongly dependent by the drug exposure time. The
      RIF/LZD combination accomplished a bacteriostatic effect in the reference strain
      and susceptible isolates. For the RIF resistant isolates, the RIF/LZD combination
      did not enhance the effect in killing bacillus. In this sense, additional, in
      vitro and in vivo studies are needed to evaluate the effect of RIF/LZD
      combination in order to better understand the adjunctive action of LZD in the
      treatment of TB and prevent the emergence of mutants with resistance to the
      available anti-TB drugs.

PMID- 28454647
TI  - Genotyping and rifampicin and isoniazid resistance in Mycobacterium bovis strains
      isolated from the lymph nodes of slaughtered cattle.
AB  - In developing nations, 10-20% of the human cases of tuberculosis are caused by
      Mycobacterium bovis. However, this percentage may be underestimated because most
      laboratories in developing countries do not routinely perform mycobacterial
      cultures, and only a few have the systems in place to identify M. bovis. There
      are few studies investigating genotypic diversity and drug resistance in M. bovis
      from animal and/or human infections. The genotypic diversity of M. bovis strains
      obtained from bovine lymph nodes were investigated by spacer oligonucleotide
      typing (spoligotyping) and mycobacterial interspersed repetitive unit-variable
      number tandem repeat typing (MIRU-VNTR). The phenotypic resistance to isoniazid
      and rifampicin and MIC values of the isolates were determined using the resazurin
      microtiter assay plate method (REMA). The evaluation of the possible genetic
      basis for such resistance was performed with GenoType MTBDRplus. Sixty-seven
      isolates were obtained, of which 11 (16%) were MDR-TB, 8 (12%) were isoniazid
      resistant, and 2 (3%) were rifampicin-resistant. Mutations associated with drug
      resistance were not found. Genotyping techniques enabled the grouping of the
      strains into 12 clusters and 21 isolates with unique profiles. The high frequency
      of M. bovis reinforces the impact of the pathogen as a major causal agent of
      bovine tuberculosis in the study area. The resistance of the strains to drugs
      used for first-line treatment of human tuberculosis raises public health
      concerns. Further studies are required to elucidate the basis of drug resistance
      and genotypic diversity in M. bovis.

PMID- 28454648
TI  - The SIGLEC14 null allele is associated with Mycobacterium tuberculosis- and BCG
      induced clinical and immunologic outcomes.
AB  - Humans exposed to Mycobacterium tuberculosis (Mtb) have variable susceptibility
      to tuberculosis (TB) and its outcomes. Siglec-5 and Siglec-14 are members of the
      sialic-acid binding lectin family that regulate immune responses to pathogens
      through inhibitory (Siglec-5) and activating (Siglec-14) domains. The SIGLEC14
      coding sequence is deleted in a high proportion of individuals, placing a SIGLEC5
      like gene under the expression of the SIGLEC14 promoter (the SIGLEC14 null
      allele) and causing expression of a Siglec-5 like protein in monocytes and
      macrophages. We hypothesized that the SIGLEC14 null allele was associated with
      Mtb replication in monocytes, T-cell responses to the BCG vaccine, and clinical
      susceptibility to TB. The SIGLEC14 null allele was associated with protection
      from TB meningitis in Vietnamese adults but not with pediatric TB in South
      Africa. The null allele was associated with increased IL-2 and IL-17 production
      following ex-vivo BCG stimulation of blood from 10 week-old South African infants
      vaccinated with BCG at birth. Mtb replication was increased in THP-1 cells
      overexpressing either Siglec-5 or Siglec-14 relative to controls. To our
      knowledge, this is the first study to demonstrate an association between SIGLEC
      expression and clinical TB, Mtb replication, or BCG-specific T-cell cytokines.

PMID- 28454649
TI  - Variable BCG efficacy in rhesus populations: Pulmonary BCG provides protection
      where standard intra-dermal vaccination fails.
AB  - M.bovis BCG vaccination against tuberculosis (TB) notoriously displays variable
      protective efficacy in different human populations. In non-human primate studies
      using rhesus macaques, despite efforts to standardise the model, we have also
      observed variable efficacy of BCG upon subsequent experimental M. tuberculosis
      challenge. In the present head-to-head study, we establish that the protective
      efficacy of standard parenteral BCG immunisation varies among different rhesus
      cohorts. This provides different dynamic ranges for evaluation of investigational
      vaccines, opportunities for identifying possible correlates of protective
      immunity and for determining why parenteral BCG immunisation sometimes fails. We
      also show that pulmonary mucosal BCG vaccination confers reduced local pathology
      and improves haematological and immunological parameters post-infection in
      animals that are not responsive to induction of protection by standard intra
      dermal BCG. These results have important implications for pulmonary TB
      vaccination strategies in the future.

PMID- 28454651
TI  - Clinical evaluation of the Abbott RealTime MTB Assay for direct detection of
      Mycobacterium tuberculosis-complex from respiratory and non-respiratory samples.
AB  - Rapid and reliable diagnosis is crucial for correct management of tuberculosis.
      The Abbott RealTime MTB Assay represents a novel qualitative real-time PCR assay
      for direct detection of M. tuberculosis-complex (MTB) DNA from respiratory
      samples. The test targets two highly conserved sequences, the multi-copy
      insertion element IS6110 and the protein antigen B (PAB) gene of MTB, allowing
      even the detection of IS6610-deficient strains. We evaluated this commercial
      diagnostic test by analyzing 200 respiratory and, for the first time, 87 non
      respiratory clinical specimens from our tertiary care institution and compared
      its results to our IS6110-based in-house real-time PCR for MTB as well as MTB
      culture. Overall sensitivity for Abbott RealTime MTB was 100% (19/19) in smear
      positive and 87.5% (7/8) in smear negative specimens, while the specificity of
      the assay was 100% (260/260). For both non-respiratory smear positive and smear
      negative specimens Abbott RealTime MTB tests showed 100% (8/8) sensitivity and
      100% (8/8) specificity. Cycle threshold (Ct) value analysis of 16 MTB positive
      samples showed a slightly higher Ct value of the Abbott RealTime MTB test
      compared to our in-house MTB assay (mean delta Ct = 2.55). In conclusion, the
      performance of the new Abbott RealTime MTB Assay was highly similar to culture
      and in-house MTB PCR. We document successful analysis of 87 non-respiratory
      samples with the highly automated Abbott RealTime MTB test with no inhibition
      observed.

PMID- 28454650
TI  - Significant under expression of the DosR regulon in M. tuberculosis complex
      lineage 6 in sputum.
AB  - Mycobacterium africanum lineage (L) 6 is an important pathogen in West Africa,
      causing up to 40% of pulmonary tuberculosis (TB). The biology underlying the
      clinical differences between M. africanum and M. tuberculosis sensu stricto
      remains poorly understood. We performed ex vivo expression of 2179 genes of the
      most geographically dispersed cause of human TB, M. tuberculosis L4 and the
      geographically restricted, M. africanum L6 directly from sputa of 11 HIV-negative
      TB patients from The Gambia who had not started treatment. The DosR regulon was
      the most significantly decreased category in L6 relative to L4. Further, we
      identified nonsynonymous mutations in major DosR regulon genes of 44 L6 genomes
      of TB patients from The Gambia and Ghana. Using Lebek's test, we assessed
      differences in oxygen requirements for growth. L4 grew only at the aerobic
      surface while L6 grew throughout the medium. In the host, the DosR regulon is
      critical for M. tuberculosis in adaptation to oxygen limitation. However, M.
      africanum L6 appears to have adapted to growth under hypoxic conditions or to
      different biological niches. The observed under expression of DosR in L6 fits
      with the genomic changes in DosR genes, microaerobic growth and the association
      with extrapulmonary disease.

PMID- 28454652
TI  - Selection, characterization, and application of DNA aptamers for detection of
      Mycobacterium tuberculosis secreted protein MPT64.
AB  - Rapid detection of Mycobacterium tuberculosis (Mtb), an etiological agent of
      tuberculosis (TB), is important for global control of this disease. Aptamers have
      emerged as a potential rival for antibodies in therapeutics, diagnostics and
      biosensing due to their inherent characteristics. The aim of the current study
      was to select and characterize single-stranded DNA aptamers against MPT64
      protein, one of the predominant secreted proteins of Mtb pathogen. Aptamers
      specific to MPT64 protein were selected in vitro using systematic evolution of
      ligands through exponential enrichment (SELEX) method. The selection was started
      with a pool of ssDNA library with randomized 40-nucleotide region. A total of 10
      cycles were performed and seventeen aptamers with unique sequences were
      identified by sequencing. Dot Blot analysis was performed to monitor the SELEX
      process and to conduct the preliminary tests on the affinity and specificity of
      aptamers. Enzyme linked oligonucleotide assay (ELONA) showed that most of the
      aptamers were specific to the MPT64 protein with a linear correlation of R2 =
      0.94 for the most selective. Using Surface Plasmon Resonance (SPR), dissociation
      equilibrium constant KD of 8.92 nM was obtained. Bioinformatics analysis of the
      most specific aptamers revealed the existence of a conserved as well as distinct
      sequences and possible binding site on MPT64. The specificity was determined by
      testing non-target ESAT-6 and CFP-10. Negligible cross-reactivity confirmed the
      high specificity of the selected aptamer. The selected aptamer was further tested
      on clinical sputum samples using ELONA and had sensitivity and specificity of
      91.3% and 90%, respectively. Microscopy, culture positivity and nucleotide
      amplification methods were used as reference standards. The aptamers studied
      could be further used for the development of medical diagnostic tools and
      detection assays for Mtb.

PMID- 28454654
TI  - The diacylglycerol acyltransferase Rv3371 of Mycobacterium tuberculosis is
      required for growth arrest and involved in stress-induced cell wall alterations.
AB  - Triacylglycerol (TAG) is important to mycobacteria both as cell envelope
      component and energy reservoir. Mycobacterium tuberculosis (Mtb) genome encodes
      at least 15 putative TAG synthase (tgs)s. We report that one of these genes,
      Rv3371, specific to pathogenic mycobacteria, when expressed in M. smegmatis leads
      to modifications in colony morphotype, bacterial architecture, cell surface
      properties and elevated TAG levels. Rv3371 was found to largely localize in the
      cell membrane. The Rv3371 promoter is minimally active during exponential growth
      in vitro, however, is up-regulated under stationary phase, hypoxia, nutrient
      starvation, nitrosative stress, low iron, in IFN-gamma activated macrophages and
      infected mice. The low iron-induced expression of Rv3371 is likely due to the de
      repression by Rv1404, which is probably activated by ideR. An Rv3371 deletion
      mutant of Mtb showed impaired non-replicating persistence in vitro and altered
      sensitivity to anti-mycobacterial drugs. In low iron medium, the Rv3371 deletion
      mutant showed reduced formation of TAG containing extracellular vesicles.
      Therefore Rv3371 is likely involved in Mtb growth arrest and cell wall
      alterations during persistence.

PMID- 28454653
TI  - Strains of Mycobacterium tuberculosis transmitting infection in Brazilian
      households and those associated with community transmission of tuberculosis.
AB  - Molecular epidemiologic studies have shown that the dynamics of tuberculosis
      transmission varies geographically. We sought to determine which strains of
      Mycobacterium tuberculosis (MTB) were infecting household contacts (HHC), and
      which were causing clusters of tuberculosis (TB) disease in Vitoria-ES, Brazil. A
      total of 741 households contacts (445 TST +) and 139 index cases were
      characterized according to the proportion of contacts in each household that had
      a tuberculin skin test positive: low (LT) (<=40% TST+), high (HT) (>=70% TST+)
      and (40-70% TST+) intermediate (IT) transmission. IS6110-RFLP and spoligotyping
      analysis were performed only 139 MTB isolates from index cases and 841 community
      isolates. Clustering occurred in 45% of the entire study population. There was no
      statistically significant association between MTB household transmission category
      and clustering. Within the household study population, the proportion of clusters
      in HT and LT groups was similar (31% and 36%, respectively; p = 0.82). Among
      index cases isolates associated with households demonstrating TST conversion, the
      frequency of unique pattern genotypes was higher for index cases of the LT
      compared to HT households (p = 0.03). We concluded that clusters and lineages
      associated with MTB infection in HT households had no proclivity for increased
      transmission of TB in the community.

PMID- 28454655
TI  - Toll-like receptor (TLR) diversity influences mycobacterial growth in African
      buffalo.
AB  - Understanding the role of wildlife in the maintenance or spread of emerging
      infectious diseases is a growing priority across the world. Bovine tuberculosis
      (BTB) is a chronic, infectious disease caused by Mycobacterium bovis (M. bovis).
      BTB is widespread within game reserves in southern Africa, and within these
      ecosystems the primary wildlife host of this disease is the African buffalo. We
      used a modified bacterial killing assay for mycobacteria to investigate the
      effect of Toll-like receptor (TLR) genetic diversity and demographic parameters
      on the ability of African buffalo to restrict mycobacterial growth. Eosinophil
      count, time delay, bovine PPD response and avian PPD response were negatively
      correlated with mycobacterial growth. TLR6 diversity and the interaction of age
      group and sex were positively correlated with mycobacterial growth. Our results
      suggest that both demographic and individual immune parameters influence the
      ability to control mycobacterial infection in African buffalo. TLR6 diversity is
      particularly interesting as this locus has also shown associations with BTB in
      cattle, suggesting that further research into the effects, selection and role of
      TLR6 variants in bovine tuberculosis will be productive.

PMID- 28454656
TI  - Selection and identification of specific glycoproteins and glycan biomarkers of
      macrophages involved in Mycobacterium tuberculosis infection.
AB  - Macrophages are the primary host target cells of Mycobacterium tuberculosis
      (M.tb). However, little is known about the changes of membrane glycopatterns of
      macrophages in response to M. tb infection. Using lectin microarrays we compared
      the differential expression of glycopatterns of macrophages upon stimulation with
      the heat-inactivated virulent M.tb H37Rv or attenuate M.tb H37Ra. We found that
      widespread alteration of macrophage membrane glycopatterns were induced by the
      heat-inactivated virulent M. tb H37Rv, as shown by the significantly changed
      binding abilities of 11 lectins (sugar binding proteins) among 40 lectins tested.
      The binding ability of the lectin ABA to macrophages showed the greatest increase
      after virulent M. tb H37Rv treatment, which suggests that the expression of N
      acetyl-d-lactosamine (ABA binding ligand Galbeta1-3GalNAc, O-link glycan) is
      mainly increased on macrophages during virulent M.tb infection. Addition of ABA
      blocked the attachment/engulfment of M. tb H37Rv, but not H37Ra, to macrophages.
      Further, increased glycosylated CD44, one of ABA-binding glycoproteins on
      macrophages, was identified by pull-down assays with ABA-agarose, followed by
      mass spectrometry and western blotting. ABA directly binds with Galbeta1-3GalNAc
      glycosylated CD44 on macrophage, and inhibits M. tb mannose-capped
      lipoarabinomannan (ManLAM) binding to glycosylated CD44. Moreover, ABA increases
      IL-6, but reduces IL-10 production of ManLAM-treated macrophages and inhibits M.
      tb H37Rv-induced necrosis in macrophages. Our study will help to reveal the
      mechanism of pathogenicity and virulence of M. tb from a new perspective and
      provide a potential new diagnostic and therapeutic strategy for tuberculosis
      based on glycopatterns, ABA and its ligand Galbeta1-3GalNAc-glycosylated CD44
      target molecule on macrophage.

PMID- 28454657
TI  - Vitamin D and Atopy.

PMID- 28454658
TI  - Managing hereditary breast cancer risk in women with and without ovarian cancer.
AB  - Current guidelines recommend that all women with ovarian cancer undergo germline
      genetic testing for BRCA1/2. Increasingly, genetic testing is being performed via
      panels that include other genes that confer a high or moderate risk of breast
      cancer. In addition, many women with a family history of breast or ovarian cancer
      are not found to have a mutation, but may have increased risk of breast cancer
      for which surveillance and risk reduction strategies are indicated. This review
      discusses how to assess and manage an increased risk of breast cancer through
      surveillance, preventive medications, and risk-reducing surgery. Assessing and
      managing the increased risk of breast cancer in BRCA1/2 mutation carriers after a
      diagnosis of ovarian cancer can be challenging. For the first few years after an
      ovarian cancer diagnosis, BRCA1/2 mutation carriers have a relatively low risk of
      breast cancer, and their prognosis is largely determined by the ovarian cancer.
      However, if these women remain in remission after two years, the risk of breast
      cancer becomes comparable with, and in some cases exceeds, their risk of ovarian
      cancer recurrence. For these women, breast cancer surveillance and risk reduction
      becomes important to their overall health. Specifically, for BRCA1/2 carriers who
      are diagnosed with early-stage ovarian cancer, we recommend regular breast cancer
      surveillance and consideration of risk reduction with medication and/or
      prophylactic mastectomy. For women with advanced ovarian cancer who do not
      achieve remission, breast cancer surveillance or prophylaxis is not of value.
      However, among carriers with more favorable advanced disease, it is reasonable to
      initiate breast cancer surveillance. Patients with less favorable advanced stage
      disease who achieve sustained remission (>2-5years) should also consider more
      aggressive strategies for breast cancer screening and prevention. For mutation
      carriers who remain in remission after five years, prophylactic mastectomy can be
      considered.

PMID- 28454659
TI  - Impact of primary platinum-free interval and BRCA1/2 mutation status on treatment
      and survival in patients with recurrent ovarian cancer.
AB  - OBJECTIVE: To understand the relationship between primary platinum-free interval
      (PFI), BRCA mutation status, and overall survival (OS) in patients with recurrent
      ovarian cancer receiving multiple lines of therapy in a multicenter, community
      based, retrospective observational cohort study of adult patients with stage III
      IV high-grade ovarian cancer. METHODS: Data were retrospectively obtained from
      the electronic health record (EHR) of a US community oncology network, including
      patient characteristics, subsequent treatments, primary PFI, and BRCA status. OS
      was analyzed by the Kaplan-Meier method, stratified by primary PFI and BRCA
      status. RESULTS: 750 patient charts were reviewed. BRCA testing status was known
      in 267 patients (16% BRCA mutation). Among patients with identified recurrent
      disease, 41% had a primary PFI <6months and 59% had a primary PFI >=6months. Of
      second-line patients, 59% received third-line therapy, and 60% of third-line
      patients received fourth-line therapy within the period of observation. Median OS
      from the start of primary treatment for the entire population was 41.4months (95%
      CI, 39.0-48.3months). Median OS was significantly increased in patients with
      primary PFI >=6months at second-line and third-line (P<0.0001 and P=0.002,
      respectively). Survival was observed to be increased among patients with BRCA
      mutations across multiple treatment lines, although this was not statistically
      significant. CONCLUSIONS: Patients with a primary PFI >=6months demonstrated
      improved outcomes over multiple lines of therapy. BRCA status was known in 36% of
      patients, and those patients with a BRCA mutation demonstrated a trend toward
      delayed primary recurrence and improved clinical outcomes.

PMID- 28454660
TI  - Management of hepatocellular carcinoma recurrence after liver transplant is far
      from perfect.

PMID- 28454661
TI  - RECISTing the Temptation to Prematurely Stop Nivolumab.

PMID- 28454662
TI  - Adjunct Screening of NKX3.1 Expression Supports 5alpha-Reductase Inhibition
      Intervention in Prostate Cancer Active Surveillance.

PMID- 28454664
TI  - End of life and bereavement care in the intensive care unit: A need for more
      quality empirical research.

PMID- 28454663
TI  - A thematic analysis of messages posted by moderators within health-related
      asynchronous online support forums.
AB  - OBJECTIVE: To identify and describe the activities performed by online support
      community moderators. METHODS: A total of 790 messages were downloaded for
      analysis. Messages were written by 59 moderators from 6 forums that represent a
      diverse range of conditions (arthritis, complex regional pain syndrome, Crohn's
      disease, depression, diabetes and Huntington's disease). RESULTS: Thematic
      analysis revealed four themes: supportive tasks supportive tasks involve
      providing help to members, moderators sharing experiences shows how they use
      forums to fulfil their own personal support needs, making announcements about new
      discoveries and upcoming events, and administrative tasks such as enforcing rules
      and deleting spam. CONCLUSION: These results are consistent with the helper
      therapy principle and provide a new insight into the diverse and varied range of
      activities carried out by moderators. PRACTICE IMPLICATIONS: Moderators perform
      many roles, including using forums for their own support needs.

PMID- 28454666
TI  - Three-dimensional surface scanners compared with standard anthropometric
      measurements for head shape.
AB  - Three-dimensional (3D) surface imaging devices designed to capture and quantify
      craniofacial surface morphology are becoming more common in clinical
      environments. Such scanners overcome the limitations of two-dimensional
      photographs while avoiding the ionizing radiation of computed tomography. The
      purpose of this study was to compare standard anthropometric cranial measurements
      with measurements taken from images acquired with 3D surface scanners. Two 3D
      scanners of different cost were used to acquire head shape data from thirteen
      adult volunteers: M4D scan and Structure Sensor. Head circumference and cephalic
      index were measured directly on the patients as well as on 3D scans acquired with
      the two scanners. To compare head volume measurements with a gold standard,
      magnetic resonance imaging scans were used. Repeatability and accuracy of both
      devices were evaluated. Intra-rater repeatability for both scanners was excellent
      (intraclass correlation coefficients > 0.99, p < 0.001). Direct and digital
      measures of head circumference, cephalic index and head volume were strongly
      correlated (0.85 < r < 0.91, p < 0.001). Compared to direct measurements,
      accuracy was highest for M4D scan. Both 3D scanners provide reproducible data of
      head circumference, cephalic index and head volume and show a strong correlation
      with traditional measurements. However, care must be taken when using absolute
      values.

PMID- 28454665
TI  - Area racism and birth outcomes among Blacks in the United States.
AB  - There is increasing evidence that racism is a cause of poor health outcomes in
      the United States, including adverse birth outcomes among Blacks. However,
      research on the health consequences of racism has faced measurement challenges
      due to the more subtle nature of contemporary racism, which is not necessarily
      amenable to assessment through traditionally used survey methods. In this study,
      we circumvent some of these limitations by examining a previously developed
      Internet query-based proxy of area racism (Stephens-Davidowitz, 2014) in relation
      to preterm birth and low birthweight among Blacks. Area racism was measured in
      196 designated market areas as the proportion of total Google searches conducted
      between 2004 and 2007 containing the "n-word." This measure was linked to county
      level birth data among Blacks between 2005 and 2008, which were compiled by the
      National Center for Health Statistics; preterm birth and low birthweight were
      defined as <37 weeks gestation and <2500 g, respectively. After adjustment for
      maternal age, Census region, and county-level measures of urbanicity, percent of
      the Black population, education, and poverty, we found that each standard
      deviation increase in area racism was associated with relative increases of 5% in
      the prevalence of preterm birth and 5% in the prevalence of low birthweight among
      Blacks. Our study provides evidence for the utility of an Internet query-based
      measure as a proxy for racism at the area-level in epidemiologic studies, and is
      also suggestive of the role of racism in contributing to poor birth outcomes
      among Blacks.

PMID- 28454667
TI  - Optimal extent of prophylactic central neck dissection for papillary thyroid
      carcinoma: Comparison of unilateral versus bilateral central neck dissection.
AB  - OBJECTIVE: The aim of the study was to determine the optimal extent of
      prophylactic central neck dissection (pCND) in papillary thyroid carcinoma (PTC).
      MATERIALS AND METHODS: We studied 384 patients with clinically node-negative
      unilateral PTC who had undergone total thyroidectomy with pCND. Of these, 169
      patients underwent unilateral pCND, and 215, bilateral pCND. RESULTS: Age, sex,
      and TNM stage did not differ between the two groups. The rates of occult central
      lymph node metastasis were 34.3% and 37.2% in the unilateral and bilateral pCND
      groups, respectively (p = 0.558). Metastasis to the contralateral paratracheal
      lymph node occurred in 4.2% of the bilateral pCND group. Major complication rates
      did not differ between the two groups, except for transient hypoparathyroidism,
      which was higher in the bilateral group (43.7% vs. 33.7%, p = 0.047). Stimulated
      thyroglobulin and RAI ablation uptake rates were similar in the two groups, as
      were recurrence and disease-free survival. CONCLUSION: Contralateral paratracheal
      node dissection may be not indicated for prophylactic central neck dissection in
      clinically node-negative unilateral PTC because the rate of contralateral
      paratracheal node metastasis is low and transient hypoparathyroidism is higher
      following bilateral dissection.

PMID- 28454669
TI  - Synthesis and evaluation of phenylisoserine derivatives for the SARS-CoV 3CL
      protease inhibitor.
AB  - Synthesis and evaluation of new scaffold phenylisoserine derivatives connected
      with the essential functional groups against SARS CoV 3CL protease are described.
      The phenylisoserine backbone was found by simulation on GOLD software and the
      structure activity relationship study of phenylisoserine derivatives gave SK80
      with an IC50 value of 43MUM against SARS CoV 3CL R188I mutant protease.

PMID- 28454668
TI  - Choosing Wisely? Measuring the Burden of Medications in Older Adults near the End
      of Life: Nationwide, Longitudinal Cohort Study.
AB  - BACKGROUND: The burden of medications near the end of life has recently come
      under scrutiny, because several studies suggested that people with life-limiting
      illness receive potentially futile treatments. METHODS: We identified 511,843
      older adults (>65 years) who died in Sweden between 2007 and 2013 and
      reconstructed their drug prescription history for each of the last 12 months of
      life through the Swedish Prescribed Drug Register. Decedents' characteristics at
      time of death were assessed through record linkage with the National Patient
      Register, the Social Services Register, and the Swedish Education Register.
      RESULTS: Over the course of the final year before death, the proportion of
      individuals exposed to >=10 different drugs rose from 30.3% to 47.2% (P <.001 for
      trend). Although older adults who died from cancer had the largest increase in
      the number of drugs (mean difference, 3.37; 95% confidence interval, 3.35 to
      3.40), living in an institution was independently associated with a slower
      escalation (beta = -0.90, 95% confidence interval, -0.92 to -0.87). During the
      final month before death, analgesics (60.8%), anti-throm-botic agents (53.8%),
      diuretics (53.1%), psycholeptics (51.2%), and beta-blocking agents (41.1%) were
      the 5 most commonly used drug classes. Angiotensin-converting enzyme inhibitors
      and statins were used by, respectively, 21.4% and 15.8% of all individuals during
      their final month of life. CONCLUSION: Polypharmacy increases throughout the last
      year of life of older adults, fueled not only by symptomatic medications but also
      by long-term preventive treatments of questionable benefit. Clinical guidelines
      are needed to support physicians in their decision to continue or discontinue
      medications near the end of life.

PMID- 28454671
TI  - Cytotoxic steroidal saponins from Trillium kamtschaticum.
AB  - Eight new steroidal saponins, trillikamtosides K-R (1-8), along with three known
      analogues, were isolated from the whole plants of Trillium kamtschaticum. Their
      structures were unambiguously established by interpretation of spectroscopic data
      (MS and NMR) and chemical methods. Compound 1 had a rare aglycone featuring a
      skeleton of 16-oxaandrost-5-en-3-ol-17-one, which was reported for the first
      time. The isolated saponins were tested for cytotoxicities against HCT116 cells,
      and trillikamtoside R (8) was found to show the most cytotoxic effect with an
      IC50 value of 4.92MUM.

PMID- 28454670
TI  - Structure-related protein tyrosine phosphatase 1B inhibition by naringenin
      derivatives.
AB  - Naturally occurring flavonoids co-exist as glycoside conjugates, which dominate
      aglycones in their content. To unveil the structure-activity relationship of a
      naturally occurring flavonoid, we investigated the effects of the glycosylation
      of naringenin on the inhibition of enzyme systems related to diabetes (protein
      tyrosine phosphatase 1B (PTP1B) and alpha-glycosidase) and on glucose uptake in
      the insulin-resistant state. Among the tested naringenin derivatives, prunin, a
      single-glucose-containing flavanone glycoside, potently inhibited PTP1B with an
      IC50 value of 17.5+/-2.6uM. Naringenin, which lacks a sugar molecule, was the
      weakest inhibitor compared to the reference compound, ursolic acid (IC50: 5.4+/
      0.30uM). In addition, prunin significantly enhanced glucose uptake in a dose
      dependent manner in insulin-resistant HepG2 cells. Regarding the inhibition of
      alpha-glucosidase, naringenin exhibited more potent inhibitory activity (IC50:
      10.6+/-0.49uM) than its glycosylated forms and the reference inhibitor, acarbose
      (IC50: 178.0+/-0.27uM). Among the glycosides, only prunin (IC50: 106.5+/-4.1uM)
      was more potent than the positive control. A molecular docking study revealed
      that prunin had lower binding energy and higher binding affinity than glycosides
      with higher numbers of H-bonds, suggesting that prunin is the best fit to the
      PTP1B active site cavity. Therefore, in addition to the number of H-bonds
      present, possible factors affecting the protein binding and PTP1B inhibition of
      flavanones include their fit to the active site, hydrogen-bonding affinity, Van
      der Waals interactions, H-bond distance, and H-bond stability. Furthermore, this
      study clearly depicted the association of the intensity of bioactivity with the
      arrangement and characterization of the sugar moiety on the flavonoid skeleton.

PMID- 28454672
TI  - Discovery of a novel and potent class of anti-HIV-1 maturation inhibitors with
      improved virology profile against gag polymorphisms.
AB  - A new class of betulin-derived alpha-keto amides was identified as HIV-1
      maturation inhibitors. Through lead optimization, GSK8999 was identified with
      IC50 values of 17nM, 23nM, 25nM, and 8nM for wild type, Q369H, V370A, and T371A
      respectively. When tested in a panel of 62 HIV-1 isolates covering a diversity of
      CA-SP1 genotypes including A, AE, B, C, and G using a PBMC based assay, GSK8999
      was potent against 57 of 62 isolates demonstrating an improvement over the first
      generation maturation inhibitor BVM. The data disclosed here also demonstrated
      that the new alpha-keto amide GSK8999 has a mechanism of action consistent with
      inhibition of the proteolytic cleavage of CA-SP1.

PMID- 28454673
TI  - Synthesis of octapeptin C4 and biological profiling against NDM-1 and polymyxin
      resistant bacteria.
AB  - The first synthesis of octapeptin C4 was achieved using a combination of solid
      phase synthesis and off-resin cyclisation. Octapeptin C4 displayed antibiotic
      activity against multi-drug resistant, NDM-1 and polymyxin-resistant Gram
      negative bacteria, with moderate activity against Staphylococcus aureus. The
      linear analogue of octapeptin C4 was also prepared, which showed reduced
      activity.

PMID- 28454675
TI  - Maximising the impact of inactivated polio vaccines.

PMID- 28454674
TI  - Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with
      reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in
      young infants in the Dominican Republic: a phase 2, non-inferiority, observer
      blinded, randomised, and controlled dose investigation trial.
AB  - BACKGROUND: Cost and supply constraints are key challenges in the use of
      inactivated polio vaccine (IPV). Dose reduction through adsorption to aluminium
      hydroxide (Al) is a promising option, and establishing its effectiveness in the
      target population is a crucial milestone in developing IPV-Al. The aim of this
      clinical trial was to show the non-inferiority of three IPV-Al vaccines to
      standard IPV. METHODS: In this phase 2, non-inferiority, observer-blinded,
      randomised, controlled, single-centre trial in the Dominican Republic, healthy
      infants aged 6 weeks, not previously polio vaccinated, were allocated after
      computer-generated randomisation by block-size of four, to receive one of four
      IPV formulations (three-times reduced dose [1/3 IPV-Al], five-times reduced dose
      [1/5 IPV-Al], ten-times reduced dose [1/10 IPV-Al], or IPV) intramuscularly in
      the thigh at 6, 10, and 14 weeks of age. The primary outcome was seroconversion
      for poliovirus types 1, 2, and 3 with titres more than or equal to four-fold
      higher than the estimated maternal antibody titre and more than or equal to 8
      after three vaccinations. Non-inferiority was concluded if the lower two-sided
      90% CI of the seroconversion rate difference between IPV-Al and IPV was greater
      than -10%. The safety analyses were based on the safety analysis set (randomly
      assigned participants who received at least one trial vaccination) and the
      immunogenicity analyses were based on the per-protocol population. This study is
      registered with ClinicalTrials.gov registration, number NCT02347423. FINDINGS:
      Between Feb 2, 2015, and Sept 26, 2015, we recruited 824 infants. The per
      protocol population included 820 infants; 205 were randomly assigned to receive
      1/3 IPV-Al, 205 to receive 1/5 IPV-Al, 204 to receive 1/10 IPV-Al, and 206 to
      receive IPV. The proportion of individuals meeting the primary endpoint of
      seroconversion for poliovirus types 1, 2, and 3 was already high for the three
      IPV-Al vaccines after two vaccinations, but was higher after three vaccinations
      (ie, after completion of the expanded programme of immunisation schedule): 1/3
      IPV-Al 98.5% (n=202, type 1), 97.6% (n=200; type 2), and 99.5% (n=204, type 3);
      1/5 IPV-Al: 99.5% (n=204, type 1), 96.1% (n=197, type 2), and 98.5% (n=202, type
      3); and 1/10 IPV-Al: 98.5% (n=201, type 1), 94.6% (n=193, type 2), and 99.5%
      (n=203, type 3). All three IPV-Al were non-inferior to IPV, with absolute
      differences in percentage seroconversion for each poliovirus type being greater
      than -10% (1/3 IPV-Al type 1, -1.46 [-3.60 to 0.10], type 2, -0.98 [-3.62 to
      1.49], and type 3, -0.49 [-2.16 to 0.86]; 1/5 IPV-Al type 1, -0.49 [-2.16 to
      0.86], type 2, -2.45 [-5.47 to 0.27], and type 3, -1.46 [-3.60 to 0.10]; and 1/10
      IPV-Al type 1, -1.47 [-3.62 to 0.10], type 2, -3.94 [-7.28 to -0.97], and type 3,
      -0.49 [-2.17 to 0.86]). Three serious adverse events occurred that were unrelated
      to the vaccine. INTERPRETATION: The lowest dose (1/10 IPV-Al) of the vaccine
      performed well both after two and three doses. Based on these results, this new
      vaccine is under investigation in phase 3 trials. FUNDING: Bill & Melinda Gates
      Foundation.

PMID- 28454677
TI  - Clinical algorithms for the diagnosis and prognosis of interstitial lung disease
      in systemic sclerosis.
AB  - INTRODUCTION: Interstitial lung disease (ILD) is currently the primary cause of
      death in systemic sclerosis (SSc). Thoracic high-resolution computed tomography
      (HRCT) is considered the gold standard for diagnosis. Recent studies have
      proposed several clinical algorithms to predict the diagnosis and prognosis of
      SSc-ILD. OBJECTIVE: To test the clinical algorithms to predict the presence and
      prognosis of SSc-ILD and to evaluate the association of extent of ILD with
      mortality in a cohort of SSc patients. METHODS: Retrospective cohort study,
      including 177 SSc patients assessed by clinical evaluation, laboratory tests,
      pulmonary function tests, and HRCT. Three clinical algorithms, combining lung
      auscultation, chest radiography, and percentage predicted forced vital capacity
      (FVC), were applied for the diagnosis of different extents of ILD on HRCT.
      Univariate and multivariate Cox proportional models were used to analyze the
      association of algorithms and the extent of ILD on HRCT with the risk of death
      using hazard ratios (HR). RESULTS: The prevalence of ILD on HRCT was 57.1% and 79
      patients died (44.6%) in a median follow-up of 11.1 years. For identification of
      ILD with extent >=10% and >=20% on HRCT, all algorithms presented a high
      sensitivity (>89%) and a very low negative likelihood ratio (<0.16). For
      prognosis, survival was decreased for all algorithms, especially the algorithm C
      (HR = 3.47, 95% CI: 1.62-7.42), which identified the presence of ILD based on
      crackles on lung auscultation, findings on chest X-ray, or FVC <80%. Extensive
      disease as proposed by Goh et al. (extent of ILD > 20% on HRCT or, in
      indeterminate cases, FVC < 70%) had a significantly higher risk of death (HR =
      3.42, 95% CI: 2.12-5.52). Survival was not different between patients with extent
      of 10% or 20% of ILD on HRCT, and analysis of 10-year mortality suggested that a
      threshold of 10% may also have a good predictive value for mortality. However,
      there is no clear cutoff above which mortality is sharply increased. CONCLUSION:
      Clinical algorithms had a good diagnostic performance for extents of SSc-ILD on
      HRCT with clinical and prognostic relevance (>=10% and >=20%), and were also
      strongly related to mortality. Non-HRCT-based algorithms could be useful when
      HRCT is not available. This is the first study to replicate the prognostic
      algorithm proposed by Goh et al. in a developing country.

PMID- 28454676
TI  - Effects of monosulfuron-ester on metabolic processes of nitrogen-fixing
      cyanobacteria Anabaena flos-aquae and Anabaena azotica.
AB  - Presence of the relatively new sulfonylurea herbicide monosulfuron-ester at 0.03
      300nmol/L affected the growth of two non-target nitrogen-fixing cyanobacteria
      (Anabaena flos-aquae and Anabaena azotica) and substantially inhibited in vitro
      Acetolactate synthase activity, with IC50 of 3.3 and 101.3nmol/L for A. flos
      aquae and A. azotica, respectively. Presenting in 30-300nmol/L, it inhibited
      protein synthesis of the cyanobacteria with less amino acids produced as its
      concentration increased. Our findings support the view that monosulfuron-ester
      toxicity in both nitrogen-fixing cyanobacteria is due to its interference with
      protein metabolism via inhibition of branch-chain amino acid biosynthesis, and
      particularly Acetolactate synthase activity.

PMID- 28454678
TI  - Turning Over a New Leaf in Lipid Droplet Biology.
AB  - Lipid droplets (LDs) in plants have long been viewed as storage depots for
      neutral lipids that serve as sources of carbon, energy, and lipids for membrane
      biosynthesis. While much of our knowledge of LD function in plants comes from
      studies of oilseeds, a recent surge in research on LDs in non-seed cell types has
      led to an array of new discoveries. It is now clear that both evolutionarily
      conserved and kingdom-specific mechanisms underlie the biogenesis of LDs in
      eukaryotes, and proteomics and homology-based approaches have identified new
      protein players. This review highlights some of these recent discoveries and
      other new areas of plant LD research, including their role in stress responses
      and as targets of metabolic engineering strategies aimed at increasing oil
      content in bioenergy crops.

PMID- 28454679
TI  - A pilot study comparing custom contoured and planar support surfaces for pressure
      ulcer risk over the heels for night time postural management using interface
      pressure mapping and discomfort scores.
AB  - PURPOSE: Custom contouring techniques are effective for reducing pressure ulcer
      risk in wheelchair seating. These techniques may assist the management of
      pressure ulcer risk during sleep for night time postural management. OBJECTIVES:
      To investigate the effectiveness of custom contoured night time postural
      management components against planar support surfaces for pressure ulcer risk
      measures over the heels. METHOD: Supine posture was captured from five healthy
      participants using vacuum consolidation and 3-dimensional laser scanning. Custom
      contoured abduction wedges were carved from polyurethane and chipped foams.
      Pressure mapping and the visual analog scale were used to evaluate the
      effectiveness of the contoured foams in reducing pressure and discomfort under
      the posterior heel against standard planar support surfaces. RESULTS: Custom
      contoured shapes significantly reduced interface pressures (p < 0.05) and
      discomfort scores (p < 0.05) when compared to planar support surfaces.
      Polyurethane foam was the most effective material but it did not differ
      significantly from chipped foam. Linear regression revealed a significant
      relationship between the Peak Pressure Index and discomfort scores (r = 0.997, p
      = 0.003). CONCLUSIONS: The findings of this pilot study suggested that custom
      contoured shapes were more effective than planar surfaces at reducing pressure
      ulcer risk surrogate measures over the posterior heels with polyurethane foam
      being the most effective material investigated. It is recommended that Evazote
      foam should not be used as a support surface material for night time postural
      management.

PMID- 28454680
TI  - Healing potential of zerumbone ointment on experimental full-thickness excision
      cutaneous wounds in rat.
AB  - Zerumbone is a monocyclic sesquiterpene compound. Based on report, it is the
      predominant bioactive compound from the rhizomes of Zingiber zerumbet. The study
      was undertaken to evaluate the therapeutic effects of topical zerumbone on
      excision wounds in rats. A 1% (w/w) simple ointment containing zerumbone was
      applied topically (100 mg ointment per rat) once a day on full-thickness excision
      wounds created on rats. The wound tissue was removed and used for estimation of
      antioxidant activity and to observe histopathological changes.
      Immunohistochemical staining was performed to study the expression pattern of
      vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1
      and collagen IV. Zerumbone exhibited antimicrobial activity against
      Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida
      albicans and Candida tropicali. Zerumbone ointment has potent wound healing
      capacity as evident from the wound contraction on 15th post wounding day. The
      histopathological examinations of healed wound sections showed greater tissue
      regeneration, more fibroblasts and angiogenesis in zerumbone ointment-treated
      group. VEGF, TGF-beta1 and collagen IV expression were also correlative with the
      healing pattern observed. Zerumbone possesses potent antioxidant activity by
      increasing superoxide dismutase, catalase, glutathione and decreased lipid
      peroxidation. The synergistic effects of both antimicrobial and antioxidant
      activities in zerumbone are deduced to have accelerated the wound repair. The
      results demonstrate that zerumbone possessed strong wound healing potential and
      can be exploited to accelerate excision wound healing.

PMID- 28454681
TI  - Human mesenchymal stem cells with enhanced telomerase activity acquire resistance
      against oxidative stress-induced genomic damage.
AB  - BACKGROUND: Human mesenchymal stem cells (MSC) are important tools for several
      cell-based therapies. However, their use in such therapies requires in vitro
      expansion during which MSCs quickly reach replicative senescence. Replicative
      senescence has been linked to macromolecular damage, and especially oxidative
      stress-induced DNA damage. Recent studies on the other hand, have implicated
      telomerase in the cellular response to oxidative damage, suggesting that
      telomerase has a telomere-length independent function that promotes survival.
      METHODS: Here, we studied the DNA damage accumulation and repair during in vitro
      expansion as well as after acute external oxidative exposure of control MSCs and
      MSCs that overexpress the catalytic subunit of telomerase (hTERT MSCs). RESULTS:
      We showed that hTERT MSCs at high passages have a significant lower percentage of
      DNA lesions as compared to control cells of the same passages. Additionally, less
      damage was accumulated due to external oxidative insult in the nuclei of hTERT
      overexpressing cells as compared to the control cells. Moreover, we demonstrated
      that oxidative stress leads to diverse nucleus malformations, such as
      multillobular nuclei or donut-shaped nuclei, in the control cells whereas hTERT
      MSCs showed significant resistance to the formation of such defects. Finally,
      hTERT MSCs were found to possess higher activities of the basic antioxidant
      enzymes, superoxide dismutase and catalase, than control MSCs. DISCUSSION: On the
      basis of these results, we propose that hTERT enhancement confers resistance to
      genomic damage due to the amelioration of the cell's basic antioxidant machinery.

PMID- 28454682
TI  - The adipose tissue-derived stromal vascular fraction cells from lipedema
      patients: Are they different?
AB  - BACKGROUND AIMS: Lipedema is a hormone-related disease of women characterized by
      enlargement of the extremities caused by subcutaneous deposition of adipose
      tissue. In healthy patients application of autologous adipose tissue-derived
      cells has shown great potential in several clinical studies for engrafting of
      soft tissue reconstruction in recent decades. The majority of these studies have
      used the stromal vascular fraction (SVF), a heterogeneous cell population
      containing adipose-derived stromal/stem cells (ASC), among others. Because cell
      identity and regenerative properties might be affected by the health condition of
      patients, we characterized the SVF cells of 30 lipedema patients in comparison to
      22 healthy patients. METHODS: SVF cells were analyzed regarding cell yield,
      viability, adenosine triphosphate content, colony forming units and proliferative
      capacity, as well as surface marker profile and differentiation potential in
      vitro. RESULTS: Our results demonstrated a significantly enhanced SVF cell yield
      isolated from lipedema compared with healthy patients. In contrast, the
      adipogenic differentiation potential of SVF cells isolated from lipedema patients
      was significantly reduced compared with healthy patients. Interestingly,
      expression of the mesenchymal marker CD90 and the endothelial/pericytic marker
      CD146 was significantly enhanced when isolated from lipedema patients.
      DISCUSSION: The enhanced number of CD90+ and CD146+ cells could explain the
      increased cell yield because the other tested surface marker were not reduced in
      lipedema patients. Because the cellular mechanism and composition in lipedema is
      largely unknown, our findings might contribute to a better understanding of its
      etiology.

PMID- 28454683
TI  - The Importance of Prolonged Provocation in Drug Allergy - Results From a Danish
      Allergy Clinic.
AB  - BACKGROUND: Drug provocation is the "Gold Standard" in drug allergy
      investigation. Recent studies suggest that a negative drug provocation on first
      dose should be followed by a prolonged provocation over several days. OBJECTIVE:
      To evaluate drug allergy investigations on the basis of drug provocation,
      including prolonged provocation. METHODS: Data from adult patients investigated
      for drug allergy in a Danish Allergy Clinic during the period 2010 to 2014 were
      entered into a database. Data included clinical details and results of
      provocations with suspected culprit drug (for penicillins performed only in
      specific IgE-negative patients). If provocation was negative on first dose,
      treatment was continued for 3 to 10 days. RESULTS: A total of 1,913 provocations
      were done in 1,659 patients, median age 46 years, of whom 1,237 (74.6%) were
      females. Drugs investigated were antibiotics, 1,776 (92.8%), of which 1,590
      (89.5%) were penicillins; analgesics, 59 (3.1%); local anesthetics, 33 (1.7%);
      and other drugs, 45 (2.4%). In total, 211 of 1,913 (11.0%) provocations were
      positive. Causes were antibiotics, 198 (93.8%), of which 167 (84.3%) were
      penicillins; analgesics, 7 (3.3%); local anesthetics, 0; and other drugs, 6
      (2.8%). Only 43 (20.4%) provocations were positive on first dose, whereas 95
      (45.0%) turned positive more than 3 days later. CONCLUSIONS: Only 11.0% of the
      provocations were positive. Importantly, only 1 of 5 patients tested positive on
      the first dose, indicating that prolonged exposure should always be considered
      when drug provocation is included in allergy investigations. Most provocations
      were with penicillins, reflecting the pattern of antibiotic use in Denmark, which
      differs from that in other countries, especially outside Northern Europe.

PMID- 28454684
TI  - Half of systemic reactions to allergen immunotherapy are delayed, majority
      require treatment with epinephrine.

PMID- 28454685
TI  - In Reply to 'Opioid Overuse or NSAID Underuse? A Response to the Pain Guide'.

PMID- 28454686
TI  - Opioid Overuse or NSAID Underuse? A Response to the Pain Guide.

PMID- 28454687
TI  - Development of motor coordination during joint action in mid-childhood.
AB  - The ability to act jointly with others is a hallmark of primate evolution and is
      fundamental for human development. In recent years, the study of coordination
      strategies between individuals performing joint actions has received growing
      attention. However, when, in the course of post-natal development, this cognitive
      motor function emerges is still unknown. Here, we studied dyads of peers aged 6-9
      years, as well as adult subjects, while they performed a task where the same
      action, namely, exerting hand force on an isometric joystick to move a visual
      cursor from a central toward a peripheral target, was performed in a "solo" and
      in a social "cooperative" context. The results revealed that during joint action
      planning, an attempt to synchronize one's own action with that of a partner
      emerges at 7 years of age, together with a reduction in the duration and
      variability of the reaction times. A critical time is 8 years, when "solo"
      performance reaches a high level of accuracy. From this age, another coordination
      strategy, based on the online monitoring of the peer's behavior, seems to be
      implemented during the execution of joint action. The motor and cognitive
      development occurring during childhood are discussed as possible mechanisms
      mediating, respectively, the capability and the propensity to take into account
      the peer's behavior for implementing a common action plan.

PMID- 28454688
TI  - Loma Linda Global Surgery Elective: First 1000 Cases.
AB  - OBJECTIVE: To determine the nature and volume of surgical cases being performed
      by US general surgery residents during a global surgery elective. DESIGN:
      Retrospective review of case logs from 2012 to 2016. SETTING: Malamulo Mission
      Hospital is a rural hospital in southern Malawi. PARTICIPANTS: Rotating residents
      from a US-based general surgery residency program. RESULTS: Residents performed
      12 cases per week from a variety of surgical disciplines. CONCLUSION: Global
      surgery rotations with dedicated faculty can provide excellent surgical variety
      and volume to enhance the training of residents.

PMID- 28454689
TI  - Identification of appropriate reference genes for qPCR analyses of placental
      expression of SLC7A3 and induction of SLC5A1 in porcine endometrium.
AB  - INTRODUCTION: Endometria and placentae undergo developmental changes that affect
      the stability of genes used as references for normalization of qPCR data. We
      identified genes that are stable within the porcine endometrium and placenta
      throughout pregnancy, and elucidated the temporal/spatial mRNA localization of
      the glucose and arginine transporters, solute carrier family (SLC) 5A1 and
      SLC7A3, respectively. MATERIALS AND METHODS: qPCR was performed for 10 genes
      within porcine endometria from Days 5, 11, and 15 of the estrous cycle and 11,
      15, 25, 40, 60, and 85 of pregnancy; and chorioallantois from Days 30, 35, 45,
      50, 60, and 85. Gene stability was analyzed using GeNorm and NormFinder
      algorithms. qPCR and in situ hybridization determined temporal/spatial
      localization of SLC5A1 and SLC7A3 at the uterine-placental interface. RESULTS:
      The geometric mean of TATA-binding protein (TBP), hypoxanthine phosphoribosyl
      transferase 1 (HPRT1), and tubulin alpha 1B (TUBA1B) provides acceptable
      reference values for porcine placenta. The geometric mean of TBP, beta actin
      (ACTB), and succinate dehydrogenase complex subunit A flavoprotein (SDHA) is
      acceptable for endometria. SLC5A1 is induced by estrogen in endometrial luminal
      epithelium (LE) on Days 12 and 13 of pregnancy. SLC7A3 is expressed in the
      chorion. DISCUSSION AND CONCLUSION: Using appropriate reference genes resulted in
      complementary results between qPCR and in situ hybridization techniques for
      SLC5A1 and SLC7A3 mRNAs. SLC5A1 is induced in uterine LE by estrogen of
      trophectoderm origin when the blastocyst is free-floating and dependent on
      glucose from the endometrium, and SLC7A3 is expressed by the established placenta
      to support fetal growth.

PMID- 28454690
TI  - Placental soluble fms-like tyrosine kinase expression in small for gestational
      age infants and risk for adverse outcomes.
AB  - INTRODUCTION: Soluble fms-like tyrosine kinase 1 (sFLT-1) is an anti-angiogenic
      factor implicated in the pathogenesis of preterm preeclampsia. We evaluated sFLT
      1 expression and placental pathology in pregnancies complicated by small for
      gestational age (SGA) infants (<10th percentile), without evidence of
      preeclampsia. METHODS: Clinical and histologic data were compared between groups
      with high or low sFLT-1 expression determined by immunohistochemistry on archived
      placentas. RESULTS: Nineteen of 69 placentas showed high sFLT-1 expression. The
      high sFLT-1 group had higher predelivery median systolic blood pressure (BP); 140
      (interquartile range (IQR) 133-152) vs. 126 (118-139) mm Hg (p = 0.003), and
      median diastolic BP; 87 (78-94) vs. 77.5 (71-86) mm Hg (p = 0.02). Abnormal
      umbilical Doppler abnormalities were more prevalent; 89.5% vs. 46% (p = 0.001).
      These pregnancies delivered earlier; 31.9 weeks (28.3-34.7 weeks) vs. 37.1 weeks
      (33.7-38.7 weeks) (p < 0.001), and infants had lower birthweight; 980 grams (520
      1545 grams) vs. 2087.5 grams (1455-2340 grams) (p < 0.001). Placental-weight to
      fetal-weight ratios, a marker of vascular insufficiency, was increased in the
      high sFlt-1 group: 0.18 (0.14-0.28) vs 0.15 (0.13-0.18), p = 0.03. Placentas with
      high sFLT-1 showed more decidual vasculopathy; 42.1% vs. 10.0% (p = 0.005),
      infarction; 36.8% vs. 14.0% (p = 0.048), distal villous hypoplasia; 78.9% vs.
      36.0% (p = 0.001), and fetal thrombotic vasculopathy; 47.4% vs. 16.0% (p = 0.01).
      DISCUSSION: Placental sFLT-1 expression is upregulated in approximately 28% of
      non-preeclamptic pregnancies complicated by SGA infants. These pregnancies showed
      increased placental vascular pathology, more umbilical Doppler abnormalities, and
      earlier delivery with lower birthweight. A subgroup of non-preeclamptic fetal
      growth restriction with upregulated sFlt-1 expression may share a common
      pathogenic pathway with preterm preeclampsia. This subgroup is worthy of
      additional study.

PMID- 28454691
TI  - Fetal DNA does not induce preeclampsia-like symptoms when delivered in late
      pregnancy in the mouse.
AB  - INTRODUCTION: The etiology of preeclampsia is unclear. Fetal DNA is present in
      higher concentrations in the plasma of pregnant women suffering from preeclampsia
      than in the plasma of healthy pregnant women. A previously published study has
      shown that human fetal DNA injected into pregnant mice induces preeclampsia-like
      symptoms when administered between gestation days 10-14. The aim of our
      experiment was to determine whether or not similar effects would be induced by
      administration of human and mouse fetal DNA, as well as mouse adult DNA and
      lipopolysaccharide during late pregnancy in the mouse. METHODS: Experimental
      animals were injected daily intraperitoneally during gestation days 14-18 with
      either saline - negative control, lipopolysaccharide - positive control, or
      various types of DNA. On gestation day 19, blood pressure and proteinuria were
      measured, and placental and fetal weights were recorded. RESULTS: Fetal and
      placental hypotrophy were induced only by lipopolysaccharide (p < 0.001). Neither
      fetal nor adult DNA induced changes in fetal/placental weight. None of the
      experimental groups had higher blood pressure or urinary protein in comparison to
      saline treated animals. DISCUSSION: In our experiment, we found that there was no
      effect from intraperitoneally injected human fetal DNA, mouse fetal DNA, or mouse
      adult DNA on pregnant mice. Additionally, relatively high doses of various types
      of DNA did not induce preeclampsia-like symptoms in mice when administered in
      late pregnancy. Our negative results support the hypothesis that the increase of
      fetal DNA circulating in maternal circulation during the third trimester is
      rather a consequence than a cause of preeclampsia.

PMID- 28454693
TI  - Cytogenetic features of human trophoblast cell lines SWAN-71 and 3A-subE.
AB  - Immortalization of primary cells with telomerase is thought to maintain normal
      phenotypic properties and avoid chromosomal abnormalities and other cancer
      associated changes that occur following simian virus 40 tumor antigen (SV40 Tag)
      induced immortalization. However, we report that the human telomerase reverse
      transcriptase (hTERT)-immortalized SWAN-71 trophoblast cell line has a near
      pentaploid 103~119,XXXX[cp20] karyotype. Additionally, DNA typing analysis
      indicated that SWAN-71 cells have acquired microsatellite instability. In
      comparison, the post-crisis SV40-transformed trophoblast cell line 3A-subE was
      hypertriploid 69~81,XX[cp20]. Both cell lines contained multiple specific clonal
      rearrangements. These findings emphasize the need to monitor for genetic
      instability in hTERT-immortalized cells.

PMID- 28454692
TI  - Maternal vascular malperfusion of the placental bed associated with hypertensive
      disorders in the Boston Birth Cohort.
AB  - INTRODUCTION: The associations of maternal conditions, before or during
      pregnancy, with placental lesions have not been adequately studied in
      populations. METHODS: In the Boston Birth Cohort, we evaluated associations
      between three maternal medical conditions (hypertensive disorders [HDs],
      gestational/pre-gestational diabetes and obesity), and placental histological
      findings, using a standardized classification system proposed by the Amsterdam
      Placental Workshop Group. Placental pathology diagnoses and clinical data from
      3074 mothers with clinical indications who delivered singleton live births at the
      Boston Medical Center between October 1998 and November 2013 were evaluated.
      Associations between each maternal condition and maternal vascular malperfusion
      (MVM) of the placental bed and its standardized subgroups were examined using
      multivariate logistic and multinomial regressions. RESULTS: Women with HDs
      (chronic hypertension, eclampsia, preeclampsia, HELLP syndrome) had significantly
      increased odds of MVM lesions when compared to women with no HD (aOR 2.08 95% CI
      1.74-2.50), after adjusting for demographics, substance use, diabetes and body
      mass index. No significant differences in frequencies or aORs were seen in women
      with and without diabetes, or across body mass index categories. Co-morbid
      condition patterns that included HDs were more likely to be associated with MVM
      than those without. DISCUSSION: Using a standardized classification system, we
      showed that MVM is strongly and specifically associated with maternal HDs, but
      not other maternal conditions. Additional studies are needed to confirm and
      validate our findings, and evaluate the role of maternal vascular lesions of the
      placental bed in relation to postnatal growth and development of the offspring
      and effect modifiers.

PMID- 28454694
TI  - Review on intrauterine programming: Consequences in rodent models of mild
      diabetes and mild fat overfeeding are not mild.
AB  - An adverse intrauterine programming occurs in diabetes and obesity as the
      consequence of an adverse maternal environment that affects the appropriate
      fetoplacental development and growth. Experimental models of diabetes and fat
      overfeeding have provided relevant tools to address putative mechanisms of the
      adverse intrauterine programming. The current knowledge far extends from the
      original thoughts of the resulting intrauterine programming of metabolic and
      cardiovascular diseases to a full range of alterations that affect multiple
      tissues, organs, and systems that will compromise the long-life health of the
      offspring. This review examines the postnatal effects of rodent models of mild
      diabetes and fat overfeeding, identifying the multiple organ derangements in the
      offspring resulting from mild maternal adverse conditions. In addition, the
      comparison of experimental models of severe diabetes and fat overfeeding and the
      crucial role of the placenta are discussed, providing an update of the actual
      scenario of the putative mechanisms and adverse consequences of maternal
      metabolic derangements.

PMID- 28454695
TI  - MiR133b is involved in endogenous hydrogen sulfide suppression of sFlt-1
      production in human placenta.
AB  - Increased production of soluble fms-like tyrosine kinase-1 (sFlt-1) from placenta
      is one of the major contributors to the development of preeclampsia. Our previous
      study has shown that hydrogen sulfide (H2S) inhibits sFlt-1 release in placenta.
      In the present study, we sought to investigate whether endogenous H2S affects
      sFlt-1 production and elucidate which H2S-producing enzyme is responsible for its
      effect in placenta. It was found that, besides cystathionine beta-synthase (CBS)
      and cystathionine gamma-lyase (CSE), 3-mercaptopyruvatesulfurtransferase (3-MST)
      was identified in human placenta and mainly localized in syncytiotrophoblasts.
      There was no significant difference in expression level of 3-MST among
      preeclamptic and normal placentas. Treatment of cultured syncytiotrophoblasts
      with NaHS and l-cysteine suppressed sFlt-1 mRNA expression and caused a decrease
      in sFlt-1 protein content in culture media of the cells. Transfection of
      syncytiotrophoblasts with CBS siRNA and CSE siRNA reversed the above effects of l
      cysteine. Furthermore, NaHS and l-cysteine treatment decreased the half-life of
      sFlt-1 mRNA and increased the expression of miR-133b targeting sFlt-1. MiR-133b
      expression was downregulated in preeclamptic placentas and correlated with the
      level of CBS and CSE. These results indicate that H2S is an important regulatory
      factor in sFlt-1 production in placenta. Reduced H2S generation in placenta
      contributes to development of preeclampsia by enhancing sFlt-1 production.

PMID- 28454696
TI  - Effect of glucocorticoids on mechanisms of placental angiogenesis.
AB  - The benefits of antenatal glucocorticoid (GC) treatment to promote human fetal
      lung maturation are well established. However, reports have emerged indicating
      that maternal exposure to high concentrations of circulating GCs alters placental
      and fetal development. Because many adult-onset metabolic and cardiovascular
      disorders have their origins in utero, the importance of prenatal conditions
      should be considered in detail. Therefore, this review aims to present an
      overview of the GC effect on placental and fetal development, specifically with
      regard to mechanisms of placental angiogenesis. We assumed that GC overexposure
      affects fetal development by altering placental angiogenesis. Disturbances in the
      development of the villous tree and pathological changes in the villous vascular
      system with insufficient uteroplacental blood flow have been linked to the
      pathogenesis of intrauterine growth retardation. Moreover, low birth weight is a
      serious risk factor known to correlate with an increased risk of adult-onset
      diseases. Although there have been many circumstances in which maternal GCs are
      elevated, we focused on exogenous synthetic GCs that are applied for therapeutic
      reasons. However, some questions about the use of steroids remain unanswered,
      which will require further studies that lead us to review alterations in
      placental angiogenesis under the perspective of GC overexposure.

PMID- 28454697
TI  - Tissue differences in DNA methylation changes at AHRR in full term low birth
      weight in maternal blood, placenta and cord blood in Chinese.
AB  - INTRODUCTION: Very few study addressed the relationship between Aryl-hydrocarbon
      receptor repressor (AHRR) DNA methylation and low birth weight, especially in
      multiple tissues of mother-infant pairs. In this study, we aimed to investigate
      AHRR DNA methylation modification in cord blood, placenta and maternal blood
      between full term low birth weight (FT-LBW) and full term normal birth weight (FT
      NBW) newborns. METHODS: We enrolled 90 FT-LBW and 90 FT-NBW mother-infant pairs,
      of which all placenta and cord blood samples were collected while 45 maternal
      blood samples of each group were collected. We measured AHRR DNA methylation
      (Chr5: 373013-373606) using Sequenom MassARRAY, and assessed associations between
      AHRR DNA methylation and FT-LBW using logistic regression adjusting for maternal
      age, education, family income, delivery mode, and passive smoking. RESULTS: FT
      LBW babies had 3% lower methylation at Chr5: 373378 (CpG 13) in cord blood, and 4
      9% higher methylation levels at Chr5: 373315, 373378, 373423, 373476 and
      373490/373494 (CpG 10; 13; 15; 16; 17/18 respectively) in maternal blood,
      comparing with FT-NBW. The methylation of Chr5: 373378 (CpG 13) remained
      significant association with FT-LBW both in cord blood (OR = 0.90; 95% CI: 0.82,
      0.98) and maternal blood (OR = 1.14; 95% CI: 1.04, 1.25) further adjusting for
      each other in the same model. We observed no significant difference at any CpG
      sites in placenta. DISCUSSION: AHRR DNA methylation of cord and maternal blood
      might be independently associated with FT-LBW in different ways.

PMID- 28454698
TI  - Placental pathology and clinical trials: Histopathology data from prior and study
      pregnancies may improve analysis.
AB  - Placental pathology may explain adverse outcomes and reveal likely recurrent
      lesions. Stratifying women into intervention arms of a perinatal trial on the
      basis of the placental histopathological findings of the index pregnancy and
      evaluating the effect of the interventions against the placental findings at
      conclusion of a trial may enhance the trial. The Cochrane Central Register of
      Controlled Trials with "obstetrics" or "perinatal" in the Title, Abstract, or
      Keywords published in 2015 were classified as to whether placental pathological
      findings from a previous pregnancy could have been used to stratify the women
      into the trial and placental pathology (findings) at the end of the study trial
      could have explained differences in the trial results, and whether these were
      performed. Two hundred and twenty three of the 275 studies were not relevant.
      Placental pathology was an outcome measure in 2 of the remaining 52 studies.
      Seven trials could have benefitted by stratifying women based on previous
      placental pathology findings, and placental pathology findings at the end of the
      trial could have explained the trial results but in none of them were these
      performed. There were 30 trials where placental pathology could have provided an
      explanation for the result but review of the pathology was not undertaken in any.
      In the remaining 13 trials, placental pathology was unlikely to be an influence
      before or after the trial; however, placental pathology would have been of
      interest or be indicated in most of them. Placental pathology appears to be
      omitted from perinatal clinical trials. Seventy-four percent (37 of 50) could
      have benefitted by using placental pathology results of a prior pregnancy to
      stratify women into intervention arms or incorporating placental pathology
      results in the evaluation of the interventions.

PMID- 28454699
TI  - Altered placental tryptophan metabolic pathway in human fetal growth restriction.
AB  - INTRODUCTION: Tryptophan is a substrate for kynurenine pathway metabolism in the
      placenta. We investigated if kynurenine metabolites change over gestation, if
      they are different between pregnancies with normal and fetal growth restriction
      (FGR), and if the oxygen environment modulated kynurenine pathway activity in the
      human placenta. METHODS: Tryptophan, kynurenine, and downstream kynurenine
      metabolites were determined in maternal venous blood, umbilical cord blood, and
      placental samples obtained in 1st and 3rd trimester pregnancies including FGR,
      and in the media of placental explants incubated with 20% or 5-8% O2 for 24, 48
      or 72 h. RESULTS: All the major kynurenine metabolites were present in cord
      blood, and in general were higher than in maternal blood. IDO and TDO mRNA and
      protein expression, responsible for kynurenine production from tryptophan, were
      significantly lower in placentas from FGR pregnancies compared with control.
      Explants prepared from 1st and 3rd trimester placentas actively produced all the
      major kynurenine pathway metabolites which, together with expression of IDO, TDO,
      KYN-OHase and 3HAO mRNAs, were significantly lower after 24 h exposure to 5-8% O2
      compared to 20% O2 CONCLUSIONS: Expression and activity of the kynurenine pathway
      is present in the placenta from early gestation, and is down-regulated by hypoxia
      and in FGR pregnancies.

PMID- 28454700
TI  - What is the impact of placental tissue damage after laser surgery for twin-twin
      transfusion syndrome? A secondary analysis of the Solomon trial.
AB  - BACKGROUND: The introduction of the Solomon technique for the treatment of twin
      twin transfusion syndrome (TTTS) increased placental exposure to laser energy.
      This study aims to identify the impact of power and energy used in laser
      treatment on placental tissue and pregnancy outcome. METHODS: Pictures of all dye
      injected placentas since the start of the Solomon trial were analyzed. Placental
      damage was scored using a grading system including visual scar depth and affected
      proportion of the vascular equator. Parameters analyzed included laser power and
      total energy, gestational age (GA) at laser, GA at birth, laser-to-delivery
      interval and preterm prelabor rupture of membranes (PPROM). RESULTS: We included
      122 cases in the analysis. More placental damage occurred more often in the
      Solomon group (42%) compared to the selective group (15%) (p < 0.001). In
      multivariate analysis, more placental damage was associated with higher laser
      energy (regression coefficient B 0.002) but not with higher power setting
      (regression coefficient B -0.442). More damage was associated with earlier GA at
      birth (regression coefficient B -0.167), higher incidence of PPROM <32 weeks
      (regression coefficient B 0.003) and a shorter laser-to-delivery interval
      (regression coefficient B -0.168). CONCLUSIONS: Placental damage is positively
      associated with more laser energy but negatively associated with higher power
      setting. More placental damage was associated with a lower GA at birth, shorter
      laser-to-delivery interval and higher PPROM rate. Whether these results should
      lead to a change in surgical technique requires more research, both further ex
      vivo experiments on human placentas and clinical studies.

PMID- 28454701
TI  - Expression profiling of maternal plasma and placenta microRNAs in preeclamptic
      pregnancies by microarray technology.
AB  - Preeclampsia (PE) is one of the leading causes of maternal and fetal morbidity
      and mortality, occurring usually in the second half of pregnancy and affecting
      approximately 5-8% of pregnancies in the world. miRNAs play critical role in the
      regulation of placental development processes. We aimed to determine specific
      novel miRNAs for early diagnosis of preeclampsia which is one of the most
      dangerous pregnancy diseases. In this study 72 samples, maternal age 22 <= and
      <=36, have been analyzed; maternal plasma and placental miRNAs were isolated from
      18 severe preeclampsia (sPE) patients and 18 controls, respectively. Profiling of
      human miRNAs (1368 probe) was performed in samples with Agilent v16 microarrays
      for detection of the differences in miRNA expression between two groups. The
      results were validated by using TaqMan RT-qPCR method. The analysis indicated
      that 406 of these miRNAs in all placentas and 42 of these miRNAs in all maternal
      plasma were expressed. The relative expression analysis has shown that 12 miRNAs
      (p < 0.05 and >2-fold) in maternal plasma were differentially expressed in PE and
      control group. However, five miRNAs were validated by qRT-PCR. Once validated
      miRNAs have been searched in databases for their target genes and function, it
      has been shown that there are some preeclampsia related pathways as a target such
      as angiogenesis, cardiovascular, hypertension, placental abruption and
      preeclampsia disorders. Differentially expressed and validated plasma miRNAs
      might be used as notable biomarkers for non-invasive early diagnosis of
      preeclampsia and treatment of disease.

PMID- 28454702
TI  - Creatine biosynthesis and transport by the term human placenta.
AB  - INTRODUCTION: Creatine is an amino acid derivative that is involved in preserving
      ATP homeostasis. Previous studies suggest an important role for the creatine
      kinase circuit for placental ATP turnover. Creatine is obtained from both the
      diet and endogenous synthesis, usually along the renal-hepatic axis. However,
      some tissues with a high-energy demand have an inherent capacity to synthesise
      creatine. In this study, we determined if the term human placenta has the
      enzymatic machinary to synthesise creatine. METHODS: Eleven placentae were
      collected following elective term caesarean section. Samples from the 4 quadrants
      of each placenta were either fixed in formalin or frozen. qPCR was used to
      determine the mRNA expression of the creatine synthesising enzymes
      arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase
      (GAMT), and the creatine transporter (SLC6A8). Protein expression of AGAT and
      GAMT was quantified by Western blot, and observations of cell localisation of
      AGAT, GAMT and SLC6A8 made with immunohistochemistry. Synthesis of
      guanidinoacetate (GAA; creatine precursor) and creatine in placental homogenates
      was determined via GC-MS and HPLC, respectively. RESULTS: AGAT, GAMT and SLC6A8
      mRNA and protein were detected in the human placenta. AGAT staining was
      identified in stromal and endothelial cells of the fetal capillaries. GAMT and
      SLC6A8 staining was localised to the syncytiotrophoblast of the fetal villi. Ex
      vivo, tissue homogenates produce both GAA (4.6 nmol mg protein-1h-1) and creatine
      (52.8 nmol mg protein-1h-1). DISCUSSION: The term human placenta has the capacity
      to synthesise creatine. These data present a new understanding of placental
      energy metabolism.

PMID- 28454703
TI  - Correlation of placental pathology and perinatal outcomes with Hemoglobin A1c in
      early pregnancy in gravidas with pregestational diabetes mellitus.
AB  - INTRODUCTION: Data on the correlation among Hemoglobin A1c (HbA1c), placental
      pathology, and perinatal outcome in the pregestational diabetic population is
      severely lacking. We believe that this knowledge will enhance the management of
      pregnancies complicated by pregestational diabetes. We hypothesize that placental
      pathology correlates with glycemic control at an early gestational age. METHODS:
      This is a retrospective cohort study conducted from 2003 to 2011 at a large
      tertiary care center. Women included had a singleton gestation, preexisting
      diabetes mellitus, and information about delivery and placental pathology
      available for review. Placental pathology and perinatal outcomes were compared
      across three groups of patients with differing HbA1c levels (<6.5%, 6.5-8.4%, and
      >=8.5%). RESULTS: 293 placentas were examined. HbA1c was measured at a mean of
      9.5week gestation. Median HbA1c was 7.5%, interquartile range 6.5%-8.9%. 23% of
      the cohort had HbA1c <6.5%, 41.9% between 6.5% and 8.4%, and 34.8% > 8.5%. BMI
      varied significantly by group (35.4 vs. 34.4 vs. 32.0 respectively, P = 0.04).
      Individual placental lesions did not vary with HbA1c levels. The incidence of
      acute chorioamnionitis differed significantly in the type 1 population and
      "distal villous hypoplasia" varied in the type 2 population. DISCUSSION: The
      results show that HbA1c values in early pregnancy are poor predictors of future
      placental pathologies. As a result, HbA1c values obtained during early gestation
      (which reflect the level of glycemic control over an extended period of time) do
      not correlate with any particular placental pathology, despite reflecting the
      potential for placental insults secondary to pre-gestational diabetes.

PMID- 28454704
TI  - The normal vaginal and uterine bacterial microbiome in giant pandas (Ailuropoda
      melanoleuca).
AB  - While the health effects of the colonization of the reproductive tracts of
      mammals by bacterial communities are widely known, there is a dearth of knowledge
      specifically in relation to giant panda microbiomes. In order to investigate the
      vaginal and uterine bacterial diversity of healthy giant pandas, we used high
      throughput sequence analysis of portions of the 16S rRNA gene, based on samples
      taken from the vaginas (GPV group) and uteri (GPU group) of these animals.
      Results showed that the four most abundant phyla, which contained in excess of
      98% of the total sequences, were Proteobacteria (59.2% for GPV and 51.4% for
      GPU), Firmicutes (34.4% for GPV and 23.3% for GPU), Actinobacteria (5.2% for GPV
      and 14.0% for GPU) and Bacteroidetes (0.3% for GPV and 10.3% for GPU). At the
      genus level, Escherichia was most abundant (11.0%) in the GPV, followed by
      Leuconostoc (8.7%), Pseudomonas (8.0%), Acinetobacter (7.3%), Streptococcus
      (6.3%) and Lactococcus (6.0%). In relation to the uterine samples,
      Janthinobacterium had the highest prevalence rate (20.2%), followed by
      Corynebacterium (13.2%), Streptococcus (19.6%), Psychrobacter (9.3%), Escherichia
      (7.5%) and Bacteroides (6.2%). Moreover, both Chao1 and abundance-based coverage
      estimator (ACE) species richness indices, which were operating at the same
      sequencing depth for each sample, demonstrated that GPV had more species richness
      than GPU, while Simpson and Shannon indices of diversity indicated that GPV had
      the higher bacterial diversity. These findings contribute to our understanding of
      the potential influence abnormal reproductive tract microbial communities have on
      negative pregnancy outcomes in giant pandas.

PMID- 28454705
TI  - Two low complexity ultra-high throughput methods to identify diverse chemically
      bioactive molecules using Saccharomyces cerevisiae.
AB  - The budding yeast S. cerevisiae is widely used as a eukaryotic model organism to
      elucidate the mechanism of action of low molecular weight compounds. This report
      describes the development of two high throughput screening methods based on cell
      viability either by monitoring the reduction of alamarBlue(r) (resazurin) or by
      direct optical measurement of cell growth. Both methods can be miniaturized to
      allow screening of large numbers of samples, and can be performed using S.
      cerevisiae in 384 and 1536-well format. The alamarBlue(r) approach achieves Z'
      values of >0.7 with signal to basal ratios of >6.5, and around 1.1 million low
      molecular weight compounds were screened, identifying approximately 25,000
      primary hits. Dose response curves generated for a subset (1930) using both
      alamarBlue(r) and optical density methods showed significant overlap. In genome
      wide haploinsufficiency profiling (HIP), 572 of these hits demonstrated a diverse
      mechanism of action, affecting >25% of all yeast strains.

PMID- 28454706
TI  - Microbial diversity of the hypersaline and lithium-rich Salar de Uyuni, Bolivia.
AB  - Salar de Uyuni, situated in the Southwest of the Bolivian Altiplano, is the
      largest salt flat on Earth. Brines of this athalassohaline hypersaline
      environment are rich in lithium and boron. Due to the ever- increasing commodity
      demand, the industrial exploitation of brines for metal recovery from the world's
      biggest lithium reservoir is likely to increase substantially in the near future.
      Studies on the composition of halophilic microbial communities in brines of the
      salar have not been published yet. Here we report for the first time on the
      prokaryotic diversity of four brine habitats across the salar. The brine is
      characterized by salinity values between 132 and 177 PSU, slightly acidic to near
      neutral pH and lithium and boron concentrations of up to 2.0 and 1.4g/L,
      respectively. Community analysis was performed after sequencing the V3-V4 region
      of the 16S rRNA genes employing the Illumina MiSeq technology. The mothur
      software package was used for sequence processing and data analysis. Metagenomic
      analysis revealed the occurrence of an exclusively archaeal community comprising
      26 halobacterial genera including only recently identified genera like
      Halapricum, Halorubellus and Salinarchaeum. Despite the high diversity of the
      halobacteria-dominated community in sample P3 (Shannon-Weaver index H'=3.12 at 3%
      OTU cutoff) almost 40% of the Halobacteriaceae-assigned sequences could not be
      classified on the genus level under stringent filtering conditions. Even if the
      limited taxonomic resolution of the V3-V4 region for halobacteria is considered,
      it seems likely to discover new, hitherto undescribed genera of the family
      halobacteriaceae in this particular habitat of Salar de Uyuni in future.

PMID- 28454707
TI  - Piriformospora indica promotes growth, seed yield and quality of Brassica napus
      L.
AB  - In current scenario, crop productivity is being challenged by decreasing soil
      fertility. To cope up with this problem, different beneficial microbes are
      explored to increase the crop productivity with value additions. In this study,
      Brassica napus L., an important agricultural economic oilseed crop with rich
      source of nutritive qualities, was interacted with Piriformospora indica, a
      unique root colonizing fungus with wide host range and multifunctional aspects.
      The fungus-treated plants showed a significant increase in agronomic parameters
      with plant biomass, lodging-resistance, early bolting and flowering, oil yield
      and quality. Nutritional analysis revealed that plants treated by P. indica had
      reduced erucic acid and glucosinolates contents, and increased the accumulation
      of N, Ca, Mg, P, K, S, B, Fe and Zn elements. Low erucic acid and glucosinolates
      contents are important parameters for high quality oil, because oils high in
      erucic acid and glucosinolates are considered undesirable for human nutrition.
      Furthermore, the expression profiles of two encoding enzyme genes, Bn-FAE1 and
      BnECR, which are responsible for regulating erucic acid biosynthesis, were down
      regulated at mid- and late- life stages during seeds development in colonized
      plants. These results demonstrated that P. indica played an important role in
      enhancing plant growth, rapeseed yield and quality improvement of B. napus.

PMID- 28454708
TI  - Functional characterisation of Burkholderia pseudomallei biotin protein ligase: A
      toolkit for anti-melioidosis drug development.
AB  - Burkholderia pseudomallei (Bp) is the causative agent of melioidosis. The
      bacterium is responsible for 20% of community-acquired sepsis cases and 40% of
      sepsis-related mortalities in northeast Thailand, and is intrinsically resistant
      to aminoglycosides, macrolides, rifamycins, cephalosporins, and
      nonureidopenicillins. There is no vaccine and its diagnosis is problematic.
      Biotin protein ligase (BirA) which is essential for fatty acid synthesis has been
      proposed as a drug target in bacteria. Very few bacterial BirA have been
      characterized, and a better understanding of these enzymes is necessary to
      further assess their value as drug targets. BirA within the Burkholderia genus
      have not yet been investigated. We present for the first time the cloning,
      expression, purification and functional characterisation of the putative Bp BirA
      and orthologous B. thailandensis (Bt) biotin carboxyl carrier protein (BCCP)
      substrate. A GFP-tagged Bp BirA was produced and applied for the development of a
      high-throughput (HT) assay based on our differential scanning fluorimetry of GFP
      tagged proteins (DSF-GTP) principle as well as an electrophoretic mobility shift
      assay. Our biochemical data in combination with the new HT DSF-GTP and
      biotinylation activity assay could facilitate future drug screening efforts
      against this drug-resistant organism.

PMID- 28454709
TI  - Involvement of phenazine-1-carboxylic acid in the interaction between Pseudomonas
      chlororaphis subsp. aureofaciens strain M71 and Seiridium cardinale in vivo.
AB  - Pseudomonas chlororaphis subsp. aureofaciens encompasses bacterial strains that
      effectively control phytopathogenic fungi through the production of the natural
      antibiotics named phenazines. In this work, the involvement of phenazine
      production in the interaction between the biological control agent P.
      chlororaphis subsp. aureofaciens M71 and the fungus Seiridium cardinale, a
      serious cypress pathogen, was investigated. Field trials were carried out to
      assess the role of phenazines in the control of S. cardinale in vivo. Results
      showed that P. chlororaphis subsp. aureofaciens M71 and 30-84, both able to
      produce phenazine-1-carboxylic acid (PCA), drastically reduced the canker
      development incited by S. cardinale. Conversely, strain M71b, a natural gacA
      mutant of P. chlororaphis subsp. aureofaciens M71, showed a decrease in PCA
      production and a reduction in controlling S. cardinale. These results were
      enforced by the reduction of canker size higher than 94% registered when 6MUg of
      pure PCA was directly applied on each cypress wound. Furthermore, PCA was
      detected in cypress plant tissues only when P. chlororaphis subsp. aureofaciens
      M71 was interacting with S. cardinale for 30 days. All these data support that
      the biological control of S. cardinale achieved by the application of P.
      chlororaphis subsp. aureofaciens M71 relies mainly on the ability of the
      bacterial strain to produce PCA in planta.

PMID- 28454710
TI  - Identification of putative effector genes and their transcripts in three strains
      related to 'Candidatus Phytoplasma aurantifolia'.
AB  - Molecular mechanisms underlying phytoplasma interactions with host plants are
      largely unknown. In this study attempts were made to identify effectors of three
      phytoplasma strains related to 'Ca. P. aurantifolia', crotalaria phyllody (CrP),
      faba bean phyllody (FBP), and witches' broom disease of lime (WBDL), using
      information from draft genome of peanut witches' broom phytoplasma. Seven
      putative effectors were identified in WBDL genome (SAP11, SAP21, Eff64, Eff115,
      Eff197, Eff211 and EffSAP67), five (SAP11, SAP21, Eff64, Eff99 and Eff197) in CrP
      and two (SAP11, Eff64) in FBP. No homologs to Eff64, Eff197 and Eff211 in
      phytoplasmas of other phylogenetic groups were found. SAP11 and Eff64 homologs of
      'Ca. P. aurantifolia' strains shared at least 95.9% identity and were detected in
      the three phytoplasmas, supporting their role within the group. Five of the
      putative effectors (SAP11, SAP21, Eff64, Eff115, and Eff99) were transcribed from
      total RNA extracts of periwinkle plants infected with these phytoplasmas.
      Transcription profiles of selected putative effectors of CrP, FBP and WBDL
      indicated that SAP11 transcripts were the most abundant in the three
      phytoplasmas. SAP21 transcript levels were comparable to those of SAP11 for CrP
      and not measurable for the other phytoplasmas. Eff64 had the lowest transcription
      level irrespective of sampling date and phytoplasma isolate. Eff115 transcript
      levels were the highest in WBDL infected plants. This work reports the first
      sequence information for 14 putative effectors in three strains related to 'Ca.
      P. aurantifolia', and offers novel insight into the transcription profile of five
      of them during infection of periwinkle.

PMID- 28454711
TI  - Microbial interference mitigates Meloidogyne incognita mediated oxidative stress
      and augments bacoside content in Bacopa monnieri L.
AB  - Microbial interference plays an imperative role in plant development and response
      to various stresses. However, its involvement in mitigation of oxidative stress
      generated by plant parasitic nematode in plants remains elusive. In the present
      investigation, the efficacy of microbe's viz., Chitiniphilus sp. MTN22 and
      Streptomyces sp. MTN14 single and in combinations was examined to mitigate
      oxidative stress generated by M. incognita in medicinal plant, Bacopa monnieri.
      Microbial combination with and without pathogen also enhanced the growth
      parameters along with secondary metabolites (bacoside) of B. monnieri than the
      pathogen inoculated control. The study showed that initially the production of
      hydrogen peroxide (H2O2) was higher in dual microbes infected with pathogen which
      further declined over M. incognita inoculated control plants. Superoxide
      dismutase and free radical scavenging activity were also highest in the same
      treatment which was linearly related with least lipid peroxidation and root gall
      formation in B. monnieri under the biotic stress. Microscopic visualization of
      total reactive oxygen species (ROS), H2O2, superoxide radical and programmed cell
      death in host plant further extended our knowledge and corroborated well with the
      above findings. Furthermore, scanning electron microscopy confirmed good
      microbial colonization on the host root surface around nematode penetration sites
      in plants treated with dual microbes under pathogenic stress. The findings offer
      novel insight into the mechanism adopted by the synergistic microbial strains in
      mitigating oxidative stress and simultaneously stimulating bacoside production
      under pathogenic stress.

PMID- 28454712
TI  - Transcriptome-based analysis of the saprophytic fungus Abortiporus biennis -
      response to oxalic acid.
AB  - In this study, the transcriptomic-based response of the white rot fungus
      Abortiporus biennis to oxalic acid induction was reported. The whole
      transcriptome of A. biennis was analysed using the RNA-based sequencing
      technology and Solid 5500 platform. De novo assembly of reads generated 37,719
      contigs. A molecular function for 26,280 unique transcripts was assigned. The
      analysis of the A. biennis transcriptome predicted 635 hypothetical open reading
      frames encoding carbohydrate active enzymes distributed in 122 families. 82 genes
      were identified, whose expression level was significantly changed after oxalic
      acid addition. Among them, 18 genes were up-regulated and 64 genes were down
      regulated. Genes coding for putative cellulose and hemicellulose degrading
      enzymes were predominantly up-regulated in the mycelium induced with oxalic acid;
      it was in the case of cellulases and xylanases (hemicellulases), in particular,
      beta-glucosidase and endo-1,4-beta-xylanases. On the contrary, several genes
      coding for lignolytic enzymes were down-regulated, with the significant
      repression level in the case of versatile peroxidase. Finally, we identified
      putative genes involved in oxalate metabolism. Among the transcripts detected in
      the A. biennis transcriptome, one was annotated as coding for putative oxalate
      decarboxylase (ODC) and nine transcripts were annotated as formate dehydrogenases
      (FDH). The addition of oxalic acid to the culture caused upregulation of the gene
      coding for ODC and three genes for FDH. Amongst the transcripts of putative FDH
      genes, one designated as NODE_36057, demonstrated the highest induction level
      recorded in this study after the oxalic acid addition.

PMID- 28454713
TI  - Fengycin produced by Bacillus subtilis 9407 plays a major role in the biocontrol
      of apple ring rot disease.
AB  - Apple ring rot, caused by Botryosphaeria dothidea, is a serious apple disease in
      China. Bacillus subtilis 9407 was isolated from healthy apples and showed strong
      antifungal activity against B. dothidea. To identify the primary antifungal
      compound of B. subtilis 9407 and determine its role in controlling apple ring
      rot, a transposon mutant library was constructed using TnYLB-1, and a mutant
      completely defective in antifungal activity was obtained. The gene inactivated in
      the antifungal activity mutant had 98.5% similarity to ppsB in B. subtilis subsp.
      subtilis str. 168, which encodes one of the five synthetases responsible for
      synthesizing fengycin. A markerless ppsB deletion mutant was constructed.
      Compared with the wild-type strain, lipopeptide crude extracts from DeltappsB
      showed almost no inhibition of B. dothidea mycelial growth. Furthermore, fengycin
      like lipopeptides (retention factor 0.1-0.2) that exhibited antifungal activity
      against B. dothidea were observed in the wild-type strain by thin-layer
      chromatography (TLC)-bioautography analysis, but not in DeltappsB.
      Semipreparative reverse-phase high performance liquid chromatography (RP-HPLC)
      detection revealed that DeltappsB lost the ability to synthesize fengycin. These
      results suggest that ppsB is responsible for synthesizing fengycin and that
      fengycin is the major antifungal compound produced by B. subtilis 9407 against B.
      dothidea. Moreover, a biocontrol assay showed that the control efficacy of
      DeltappsB was reduced by half compared with the wild-type strain, indicating that
      fengycin plays a major role in controlling apple ring rot disease. This is the
      first report on the use of a B. subtilis strain as a potential biological control
      agent to control apple ring rot disease by the production of fengycin.

PMID- 28454714
TI  - Growth promotion of peanut (Arachis hypogaea L.) and maize (Zea mays L.) plants
      by single and mixed cultures of efficient phosphate solubilizing bacteria that
      are tolerant to abiotic stress and pesticides.
AB  - The aims of this study were, to analyze in vitro phosphate solubilization
      activity of six native peanut bacteria and to determine the effect of single and
      mixed inoculation of these bacteria on peanut and maize plants. Ability to
      produce organic acids and cofactor PQQ, to solubilize FePO4 and AlPO4 and
      phosphatase activity were analyzed. Also, the ability to solubilize phosphate
      under abiotic stress and in the presence of pesticides of the selected bacteria
      was determined. The effect of single and mixed bacterial inocula was analyzed on
      seed germination, maize plant growth and in a crop rotation plant assay with
      peanut and maize. The six strains produced gluconic acid and five released
      cofactor PQQ into the medium. All bacteria showed ability to solubilize phosphate
      from FePO4 and AlPO4 and phosphatase activity. The ability of the bacteria to
      solubilize tricalcium phosphate under abiotic stress and in presence of
      pesticides indicated encouraging results. Bacterial inoculation on peanut and
      maize increased seed germination, plants growth and P content. Phosphate
      solubilizing bacteria used in this study showed efficient phosphate mineralizing
      and solubilization ability and would be potential P-biofertilizers for peanut and
      maize.

PMID- 28454716
TI  - Definition: Spatial neglect.

PMID- 28454715
TI  - A PCR-based method for quantifying neutrophils in human nasal secretions.
AB  - Neutrophil recruitment to the nasopharynx (NP) is a central event in resolution
      of NP-initiated microbial infections. A vigorous neutrophil response in infected
      tissues is also associated with the outcome of adverse tissue pathology.
      Therefore, differences in infection-induced tissue neutrophil numbers may
      correlate with pathogenesis events. Existing methods of quantifying neutrophils
      require evaluation of NP samples within hours of procurement as flow cytometry
      based cell quantification methods require live neutrophil cells. Therefore, we
      developed a novel RT-PCR method that could reliably quantify neutrophil counts in
      frozen NP wash samples. mRNA transcripts of the genes encoding CD16, CD18, and
      CD62L were identified as neutrophil-specific in NP samples and not significantly
      variable in response to stimulation by heat killed bacteria, and can be used to
      derive an accurate assessment of neutrophil content in a sample even in the
      presence of epithelial cells. Using flow cytometry as a comparator, the method
      was validated in human NP wash samples. We conclude that this PCR-based method
      should prove useful for providing a quantitative estimate of neutrophil
      recruitment to the NP during infection and pathogenesis.

PMID- 28454717
TI  - Errors in interception can be predicted from errors in perception.
AB  - It has been hypothesised that our actions are less susceptible to visual
      illusions than our perceptual judgements because similar information is processed
      for perception and action in separate pathways. We test this hypothesis for
      subjects intercepting a moving object that appears to move at a different speed
      than its true speed due to an illusion. The object was a moving Gabor patch: a
      sinusoidal grating of which the luminance contrast is modulated by a two
      dimensional Gaussian. We manipulated the patch's apparent speed by moving the
      grating relative to the Gaussian. We used separate two-interval forced choice
      discrimination tasks to determine how moving the grating influenced ten people's
      judgements of the object's position and velocity while they were fixating. Based
      on their perceptual judgements, and knowing that our ability to correct for
      errors that arise from relying on incorrect judgements are limited by a
      sensorimotor delay of about 100 msec, we predicted the extent to which subjects
      would tap ahead of or behind similar targets when trying to intercept them at the
      fixation location. The predicted errors closely matched the actual errors that
      subjects made when trying to intercept the targets. This finding does not support
      the two visual streams hypothesis. The results are consistent with the idea that
      the extent to which an illusion influences an action tells us something about the
      extent to which the action relies on the percept in question.

PMID- 28454718
TI  - Effects of co-administration of ketamine and ethanol on the dopamine system via
      the cortex-striatum circuitry.
AB  - AIM: Ketamine and ethanol are increasingly being used together as recreational
      drugs in rave parties. Their effects on the dopamine (DA) system remain largely
      unknown. This study aimed to investigate the effects of consuming two different
      concentrations of ketamine with and without alcohol on the DA system. MATERIALS
      AND METHODS: We employed the conditioned place preference (CPP) paradigm to
      evaluate the rewarding effects of the combined administration of two different
      doses of ketamine (30mg/kg and 60mg/kg) with ethanol (0.3156g/kg). We evaluated
      the effects of the combined drug treatment on the transcriptional output of
      tyrosine hydroxylase (TH), dopa decarboxylase (DDC), synaptosomal-associated
      protein 25 (SNAP25), and vesicular monoamine transporter 2 (VMAT2) as well as
      protein expression level of brain-derived neurotrophic factor (BDNF) in rat
      prefrontal cortex (PFC) and striatum. KEY FINDINGS: We found that rats exhibited
      a dose-dependent, drug-paired, place preference to ketamine and ethanol
      associated with an elevated DA level in the striatum but not in the PFC.
      Moreover, treatment involving low- or high-dose ketamine with or without ethanol
      caused a differential regulatory response in the mRNA levels of the four DA
      metabolism genes and the cellular protein abundance of BDNF via the cortex
      striatum circuitry. SIGNIFICANCE: This study investigated the molecular
      mechanisms that occur following the combined administration of ketamine and
      ethanol in the DA system, which could potentially lead to alterations in the
      mental status and behavior of ketamine/ethanol users. Our findings may aid the
      development of therapeutic strategies for substance abuse patients.

PMID- 28454719
TI  - Prioritizing Information during Working Memory: Beyond Sustained Internal
      Attention.
AB  - Working memory (WM) has limited capacity. This leaves attention with the
      important role of allowing into storage only the most relevant information. It is
      increasingly evident that attention is equally crucial for prioritizing
      representations within WM as the importance of individual items changes.
      Retrospective prioritization has been proposed to result from a focus of internal
      attention highlighting one of several representations. Here, we suggest an
      updated model, in which prioritization acts in multiple steps: first orienting
      towards and selecting a memory, and then reconfiguring its representational state
      in the service of upcoming task demands. Reconfiguration sets up an optimized
      perception-action mapping, obviating the need for sustained attention. This view
      is consistent with recent literature, makes testable predictions, and links WM
      with task switching and action preparation.

PMID- 28454720
TI  - A two-year dietary carcinogenicity study of cyadox in Sprague-Dawley rats.
AB  - To investigate the potential carcinogenicity of cyadox, an antimicrobial agent,
      four groups of Sprague-Dawley rats (50 rats/sex/group) were fed diets containing
      cyadox (0, 200, 600 or 2000 mg/kg) for up to two years. There were significant
      decreases in body weight, feed intake and feed efficiency in both genders during
      most of the period in the 2000 mg/kg group. Significant decreases in serum ALT
      were observed in the 2000 mg/kg group at weeks 52, 78 and 104. For the control,
      200, 600, and 2000 mg/kg groups, the tumor incidence in females was 33.3%, 37.2%,
      40.0% and 19.0%, while it in males it was 18.9%, 2.6%, 17.1% and 13.6%,
      respectively. At histopathology, no increases in tumor incidence were attributed
      to treatment with cyadox. The mild swelling and fatty degeneration in
      hepatocytes, and mild swelling and tubular necrosis in the kidney were observed
      in 2000 mg/kg group. The no-observed-effect-level (NOEL) for carcinogenicity of
      cyadox fed to rats was 2000 mg/kg diet (132.18-156.28 mg/kg b.w./day). In
      conclusion, cyadox was not carcinogenic to rats with the liver and kidney as the
      target organs, and the side chain may be involved in toxicity and carcinogenicity
      mediated by QdNOs.

PMID- 28454721
TI  - The Treatment of Brain Arteriovenous Malformation Study (TOBAS): A preliminary
      inter- and intra-rater agreement study on patient management.
AB  - OBJECT: The best management of brain arteriovenous malformation (bAVM) patients
      remains unknown. Randomized allocation may be more readily accepted when there is
      uncertainty and disagreement regarding the management of potential participants.
      In planning for a trial, we aimed to assess variability and agreement among
      physicians managing bAVM patients. METHODS: A portfolio composed of 35 patients
      was sent to 47 clinicians of various specialties managing bAVM patients. For each
      patient, physicians were asked their best management decision
      (surgery/embolization/radiosurgery/conservative), their confidence level, and
      whether they would include the patient in a randomized trial comparing
      conservative and curative management. Seven physicians, who had access to all
      images of each patient, independently responded twice, to assess inter and intra
      rater agreement using kappa statistics. RESULTS: The inter-rater agreement (30
      raters, including 16 neuroradiologists) for best management decision was only
      "fair" (kappa [95%CI]=0.210[0.157; 0.295]). Agreement remained below
      'substantial' (kappa<.6) between physicians of the same specialty, and when no
      distinctions were made between various treatments (when responses were
      dichotomized as conservative versus curative). With access to all images the
      inter-rater agreement remained fair. The intra-rater agreement reached
      "substantial" only for the dichotomized decisions. Responding clinicians were
      willing to include 54.4% of patients (mainly unruptured bAVMs) in a randomized
      trial. CONCLUSION: There is a lack of agreement among clinicians involved in the
      management of bAVM patients. In this study a substantial proportion of clinicians
      were willing to offer randomized allocation of management options to a
      substantial number of patients.

PMID- 28454722
TI  - Suprasellar atypical teratoid/rhabdoid tumor.

PMID- 28454723
TI  - Role of androgen receptor on cyclic mechanical stretch-regulated proliferation of
      C2C12 myoblasts and its upstream signals: IGF-1-mediated PI3K/Akt and MAPKs
      pathways.
AB  - OBJECTS: To detect the effects of androgen receptor (AR) on cyclic mechanical
      stretch-modulated proliferation of C2C12 myoblasts and its pathways: roles of IGF
      1, PI3K and MAPK. METHODS: C2C12 were randomly divided into five groups: un
      stretched control, six or 8 h of fifteen percent stretch, and six or 8 h of
      twenty percent stretch. Cyclic mechanical stretch of C2C12 were completed using a
      computer-controlled FlexCell Strain Unit. Cell proliferation and IGF-1
      concentration in medium were detected by CCK8 and ELISA, respectively.
      Expressions of AR and IGF-1R, and expressions and activities of PI3K, p38 and
      ERK1/2 in stretched C2C12 cells were determined by Western blot. RESULTS: 1The
      proliferation of C2C12 cells, IGF-1 concentration in medium, expressions of AR
      and IGF-1R, and activities of PI3K, p38 and ERK1/2 were increased by 6 h of
      fifteen percent stretch, while decreased by twenty percent stretch for six or 8 h
      2The fifteen percent stretch-increased proliferation of C2C12 cells was reversed
      by AR inhibitor, Flutamide. 3The increases of AR expression, activities of PI3K,
      p38 and ERK1/2 resulted from fifteen percent stretch were attenuated by IGF-1
      neutralizing antibody, while twenty percent stretch-induced decreases of the
      above indicators were enhanced by recombinant IGF-1. 4Specific inhibitors of p38,
      ERK1/2 and PI3K all decreased the expression of AR in fifteen percent and twenty
      percent of stretched C2C12 cells. CONCLUSIONS: Cyclic mechanical stretch
      modulated the proliferation of C2C12 cells, which may be attributed to the
      alterations of AR via IGF-1-PI3K/Akt and IGF-1-MAPK (p38, ERK1/2) pathways in
      C2C12 cells.

PMID- 28454724
TI  - Protein Phosphatase 1alpha enhances renal aldosterone signaling via
      mineralocorticoid receptor stabilization.
AB  - Stimulation of the mineralocorticoid receptor (MR) by aldosterone controls
      several physiological parameters including blood pressure, inflammation or
      metabolism. We previously showed that MR turnover constitutes a crucial
      regulatory step in the responses of renal epithelial cells to aldosterone. Here,
      we identified Protein Phosphatase 1 alpha (PP1alpha), as a novel cytoplasmic
      binding partner of MR that promotes the receptor activity. The RT-PCR expression
      mapping of PP1alpha reveals a high expression in the kidney, particularly in the
      distal part of the nephron. At the molecular level, we demonstrate that PP1alpha
      inhibits the ubiquitin ligase Mdm2 by dephosphorylation, preventing its
      interaction with MR. This results in the accumulation of the receptor due to
      reduction of its proteasomal degradation and consequently a greater aldosterone
      induced Na+ uptake by renal cells. Thus, our findings describe an original
      mechanism involving a phosphatase in the regulation of aldosterone signaling and
      provide new and important insights into the molecular mechanism underlying the MR
      turnover.

PMID- 28454725
TI  - Reliability and validity of active and passive pectoralis minor muscle length
      measures.
AB  - BACKGROUND: Pectoralis minor muscle length is believed to play an important role
      in shoulder pain and dysfunction. Current clinical procedures for assessing
      pectoralis minor muscle length may not provide the most useful information for
      clinical decision making. OBJECTIVE: To establish the reliability and construct
      validity of a novel technique to measure pectoralis minor muscle length under
      actively and passively lengthened conditions. DESIGN: Cross-sectional repeated
      measures. METHODS: Thirty-four healthy adults (age: 23.9, SD=1.6 years; 18
      females) participated in this study. Pectoralis minor muscle length was measured
      on the dominant arm in three length conditions: resting, actively lengthened, and
      passively lengthened. Based upon availability, two raters, out of a pool of five,
      used a caliper to measure the distance between the coracoid process and the 4th
      rib. The average of two pectoralis minor muscle length measures was used for all
      muscle length conditions and analyses. Intraclass correlation coefficients
      determined intra-and inter-rater reliability, and measurement error was
      determined via standard error of measurement and minimal detectable change.
      Construct validity was assessed by ANOVA to determine differences in muscle
      length across the three conditions. RESULTS: Our intra- and inter-rater
      reliability values across all three conditions ranged from 0.84 to 0.92 and from
      0.80 to 0.90, respectively. Significant differences (p<0.001) in muscle length
      were found among all three conditions: rest-active (3.66; SD=1.36cm), rest
      passive (4.72, SD=1.41cm), and active-passive (1.06, SD=0.47cm). CONCLUSIONS: The
      techniques described in this study for measuring pectoralis minor muscle length
      under resting and actively and passively lengthened conditions have acceptable
      reliability for clinical decision making.

PMID- 28454726
TI  - Predictive Value of Early Tumor Shrinkage and Density Reduction of Lung
      Metastases in Patients With Metastatic Colorectal Cancer Treated With
      Regorafenib.
AB  - INTRODUCTION: The benefit of regorafenib in colorectal cancer is not very
      pronounced. At present, there is lack of predictive biological or radiological
      markers. We studied if density reduction or small changes in size of lung
      metastases could be a predictive marker. METHODS: We retrospectively measured
      density in size of lung metastases of all patients included in the CORRECT and
      CONSIGN trials at our center. Contrast-enhanced CT scan at baseline and at week 8
      were compared. Data of progressive-free survival and overall survival were
      collected from the CORRECT and CONSIGN trials. RESULTS: A significant difference
      in progressive-free survival was seen in 3 groups: response or stable disease in
      size (5.36 vs. 3.96 months), response in density (6.03 vs. 2.72 months), and
      response in corrected density (6.14 vs. 3.08 months). No difference was seen for
      response in size versus stable disease or progressive disease in size. For
      overall survival, a difference was observed in the same 3 groups: response or
      stable disease in size (9.89 vs. 6.44 months), response in density (9.59 vs. 7.04
      months), and response in corrected density (9.09 vs. 7.16 months). No difference
      was seen for response in size versus stable disease or progressive disease in
      size. CONCLUSION: Density reduction in lung metastases might be a good predictive
      parameter to predict outcome for regorafenib. Early tumor progression might be a
      negative predictive factor. If further validated, density reduction and early
      tumor progression might be useful to ameliorate the cost-benefit of regorafenib.

PMID- 28454727
TI  - Proteomic approach to characterize biochemistry of meat quality defects.
AB  - Proteomics can be used to characterize quality defects including pale, soft, and
      exudative (PSE) meat (pork and poultry), woody broiler breast meat, reddish
      catfish fillets, meat toughness, and beef myoglobin oxidation. PSE broiler meat
      was characterized by 15 proteins that differed in abundance in comparison to
      normal broiler breast meat, and eight proteins were differentially expressed in
      woody breast meat in comparison to normal breast meat. Hemoglobin was the only
      protein that was differentially expressed between red and normal catfish fillets.
      However, inducing low oxygen and/or heat stress conditions to catfish fillets did
      not lead to the production of red fillets. Proteomic data provided information
      pertaining to the protein differences that exist in meat quality defects.
      However, these data need to be evaluated in conjunction with information
      pertaining to genetics, nutrition, environment of the live animal, muscle to meat
      conversion, meat quality analyses and sensory attributes to understand causality,
      protein biomarkers, and ultimately how to prevent quality defects.

PMID- 28454728
TI  - [CD30 lymphocytic infiltrate and acute generalized exanthematous pustulosis].

PMID- 28454730
TI  - 2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure
      and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical
      Competence Statement on Management of Patients With Advanced Heart Failure and
      Cardiac Transplant): A Report of the ACC Competency Management Committee.

PMID- 28454729
TI  - Activation of Parathyroid Hormone 2 Receptor Induces Decorin Expression and
      Promotes Wound Repair.
AB  - In this study, we report that TIP39, a parathyroid hormone ligand family member
      that was recently identified to be expressed in the skin, can induce decorin
      expression and enhance wound repair. Topical treatment of mice with TIP39
      accelerated wound repair, whereas TIP39-deficient mice had delayed repair that
      was associated with formation of abnormal collagen bundles. To study the
      potential mechanism responsible for the action of TIP39 in the dermis,
      fibroblasts were cultured in three-dimensional collagen gels, a process that
      results in enhanced decorin expression unless activated to differentiate to
      adipocytes, whereupon these cells reduce expression of several proteoglycans,
      including decorin. Small interfering RNA-mediated silencing of parathyroid
      hormone 2 receptor (PTH2R), the receptor for TIP39, suppressed the expression of
      extracellular matrix-related genes, including decorin, collagens, fibronectin,
      and matrix metalloproteases. Skin wounds in TIP39-/- mice had decreased decorin
      expression, and addition of TIP39 to cultured fibroblasts induced decorin and
      increased phosphorylation and nuclear translocation of CREB. Fibroblasts
      differentiated to adipocytes and treated with TIP39 also showed increased decorin
      and production of chondroitin sulfate. Furthermore, the skin of PTH2R-/- mice
      showed abnormal extracellular matrix structure, decreased decorin expression, and
      skin hardness. Thus, the TIP39-PTH2R system appears to be a previously
      unrecognized mechanism for regulation of extracellular matrix formation and wound
      repair.

PMID- 28454731
TI  - Executive Summary of the SCAI/HFSA Clinical Expert Consensus Document on the Use
      of Invasive Hemodynamics for the Diagnosis and Management of Cardiovascular
      Disease.

PMID- 28454733
TI  - Capillary electrochromatography immunoassay for alpha-fetoprotein based on
      poly(guanidinium ionic liquid) monolithic material.
AB  - Alpha-fetoprotein (AFP) is widely used as a tumor marker for the serum diagnosis
      of primary hepatoma. Sensitive detection of AFP level plays an important role in
      the early diagnosis of disease and highly reliable prediction. In this study, a
      novel non-competitive immunoassay (IA) based on poly(guanidinium ionic liquid)
      monolithic material was developed for detecting ultra trace levels of AFP in
      capillary electrochromatography (CEC) mode. The AFP was mixed with an excess
      amount of fluorescently labeled antibody. After incubation, the immunocomplex was
      separated from the free labeled antibody and detected by CEC coupled with laser
      induced fluorescence detector. Under the optimized conditions, the developed CEC
      IA performed a low detection limit of 0.05 MUg L-1 (S/N = 3) and a wide linearity
      ranging from 0.1 to 1000 MUg L-1 for AFP, which can be largely attributed to the
      high separation and enrichment efficiency of poly(guanidinium ionic liquid)
      monolithic material for the targets. The application of this method was
      demonstrated by determining AFP in human serum.

PMID- 28454734
TI  - Conservative Treatments of Ocular Melanomas: Technology Used Wisely.

PMID- 28454732
TI  - Fluvastatin Prevents Lung Adenocarcinoma Bone Metastasis by Triggering Autophagy.
AB  - Bone is one of the most preferred sites of metastasis in lung cancer. Currently,
      bisphosphonates and denosumab are major agents for controlling tumor-associated
      skeletal-related events (SREs). However, both bisphosphonates and denosumab
      significantly increase the risk for jaw osteonecrosis. Statins, 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and the most frequently
      prescribed cholesterol-lowering agents, have been reported to inhibit tumor
      progression and induce autophagy in cancer cells. However, the effects of statin
      and role of autophagy by statin on bone metastasis are unknown. In this study, we
      report that fluvastatin effectively prevented lung adenocarcinoma bone metastasis
      in a nude mouse model. We further reveal that fluvastatin-induced anti-bone
      metastatic property was largely dependent on its ability to induce autophagy in
      lung adenocarcinoma cells. Atg5 or Atg7 deletion, or 3-methyadenine (3-MA) or
      Bafilomycin A1 (Baf A1) treatment prevented the fluvastatin-induced suppression
      of bone metastasis. Furthermore, we reveal that fluvastatin stimulation increased
      the nuclear p53 expression, and fluvastatin-induced autophagy and anti-bone
      metastatic activity were mostly dependent on p53.

PMID- 28454735
TI  - Biosynthesis-inspired deracemizative production of d-luciferin by combining
      luciferase and thioesterase.
AB  - Due to the strict enantioselectivity of firefly luciferase, only d-luciferin can
      be used as a substrate for bioluminescence reactions. Unfortunately, luciferin
      racemizes easily and accumulation of nonluminous l-luciferin has negative
      influences on the light emitting reaction. Thus, maintaining the enantiopurity of
      luciferin in the reaction mixture is one of the most important demands in
      bioluminescence applications using firefly luciferase. In fireflies, however, l
      luciferin is the biosynthetic precursor of d-luciferin, which is produced from
      the L-form undergoing deracemization. This deracemization consists of three
      successive reactions: l-enantioselective thioesterification by luciferase, in
      situ epimerization, and hydrolysis by thioesterase. In this work, we introduce a
      deracemizative luminescence system inspired by the biosynthetic pathway of d
      luciferin using a combination of firefly luciferase from Luciola cruciata (LUC-G)
      and fatty acyl-CoA thioesterase II from Escherichia coli (TESB). The enzymatic
      reaction property analysis indicated the importance of the concentration balance
      between LUC-G and TESB for efficient d-luciferin production and light emission.
      Using this deracemizative luminescence system, a highly sensitive quantitative
      analysis method for l-cysteine was constructed. This LUC-G-TESB combination
      system can improve bioanalysis applications using the firefly bioluminescence
      reaction by efficient deracemization of D-luciferin.

PMID- 28454736
TI  - A new cryptic host defense peptide identified in human 11-hydroxysteroid
      dehydrogenase-1 beta-like: from in silico identification to experimental
      evidence.
AB  - BACKGROUND: Host defence peptides (HDPs) are evolutionarily conserved components
      of innate immunity. Human HDPs, produced by a variety of immune cells of
      hematopoietic and epithelial origin, are generally grouped into two families:
      beta structured defensins and variably-structured cathelicidins. We report the
      characterization of a very promising cryptic human HDP, here called GVF27,
      identified in 11-hydroxysteroid dehydrogenase-1 beta-like protein. METHODS:
      Conformational analysis of GVF27 and its propensity to bind endotoxins were
      performed by NMR, Circular Dichroism, Fluorescence and Dynamic Light Scattering
      experiments. Crystal violet and WST-1 assays, ATP leakage measurement and colony
      counting procedures were used to investigate antimicrobial, anti-biofilm,
      cytotoxicity and hemolytic activities. Anti-inflammatory properties were
      evaluated by ELISA. RESULTS: GVF27 possesses significant antibacterial properties
      on planktonic cells and sessile bacteria forming biofilm, as well as promising
      dose dependent abilities to inhibit attachment or eradicate existing mature
      biofilm. It is unstructured in aqueous buffer, whereas it tends to assume a
      helical conformation in mimic membrane environments as well as it is able to bind
      lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Notably it is not toxic
      towards human and murine cell lines and triggers a significant innate immune
      response by attenuating expression levels of pro-inflammatory interleukins and
      release of nitric oxide in LPS induced macrophages. CONCLUSION: Human GVF27 may
      offer significant advantages as leads for the design of human-specific
      therapeutics. GENERAL SIGNIFICANCE: Human cryptic host defence peptides are
      naturally no immunogenic and for this they are a real alternative for solving the
      lack of effective antibiotics to control bacterial infections.

PMID- 28454737
TI  - Characterization of beta-lactamase activity using isothermal titration
      calorimetry.
AB  - BACKGROUND: Hydrolysis of beta-lactam antibiotic by beta-lactamase is the most
      common mechanism of beta-lactam resistance in clinical isolates. Timely detection
      and characterization of beta-lactamases are therefore of utmost biomedical
      importance. Conventional spectrophotometric method is time-consuming and cannot
      provide thermodynamic information on beta-lactamases. METHODS: A new assay was
      developed for the study of beta-lactamase activity in protein solutions (Metallo
      beta-lactamase L1) and in clinical bacterial cells, based on heat-flow changes
      derived from enzymatic hydrolysis of beta-lactams using isothermal titration
      calorimetry. RESULTS: (1) The thermokinetic parameters of three antibiotics
      (penicillin G, cefazolin and imipenem) and the inhibition constant of an
      azolylthioacetamide inhibitor were determined using the calorimetric assay. The
      results from the calorimetric assays were consistent with the data from the
      spectrophotometric assay. (2) The values of heat change in the calorimetric assay
      using two clinical Escherichia coli strains correlated well with their antibiotic
      susceptibility results from the broth dilution experiment. The subtypes of beta
      lactamase were also determined in the calorimetric assay. CONCLUSIONS: The ITC
      assay is a reliable and fast method to study beta-lactamase enzyme kinetics and
      inhibition. It can also provide thermodynamic information on antibiotic
      hydrolysis, which has been taken advantage of in this work to study beta
      lactamase activity in two clinical Escherichia coli isolates. GENERAL
      SIGNIFICANCE: As the first calorimetric study of beta-lactamase activity, it may
      provide a new assay to assist biomedical validation of new beta-lactamase
      inhibitors, and also has potential applications on rapid antibiotic
      susceptibility testing and screening beta-lactamase producing bacteria.

PMID- 28454738
TI  - Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side
      effects by different mechanisms.
AB  - Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive
      dyskinesia) treatment with antipsychotics, including haloperidol, varies
      substantially among people. CYP2D can metabolize many antipsychotics and variable
      brain CYP2D metabolism can influence local drug and metabolite levels
      sufficiently to alter behavioral responses. Here we investigated a role for brain
      CYP2D in acutely and chronically administered haloperidol levels and side-effects
      in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly
      inhibited with intracerebral propranolol and/or induced by seven days of
      subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was
      investigated in rat models of acute (catalepsy) and chronic (vacuous chewing
      movements, VCMs) haloperidol side-effects. Selective inhibition and induction of
      brain, but not liver, CYP2D decreased and increased catalepsy after acute
      haloperidol, respectively. Catalepsy correlated with brain, but not hepatic,
      CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic
      haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity,
      haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D
      activity and plasma haloperidol levels were unchanged by brain CYP2D
      manipulations. Variable rat brain CYP2D alters side-effects from acute and
      chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a
      brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs.
      These data provide novel mechanistic evidence for brain CYP2D altering side
      effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting
      that variation in human brain CYP2D may be a risk factor for antipsychotic side
      effects.

PMID- 28454739
TI  - Antibodies to Shiga toxins in Brazilian cattle.
AB  - Cattle are considered a reservoir of Shiga toxin-producing Escherichia coli
      (STEC). There is no information about the presence of antibodies against Shiga
      toxins in Brazilian bovine serum. Using ELISA, all sera tested showed antibodies
      against the two main STEC virulence factors; Stx1 and Stx2. Neutralizing
      antibodies against Stx1 and/or Stx2 were detected in all but one serum. In
      conclusion, our results indicated that these animals had been exposed to STEC
      producing both toxins.

PMID- 28454740
TI  - Analysis of basophil activation in patients with aspirin-exacerbated respiratory
      disease.

PMID- 28454741
TI  - Peanut-free schools: What does it really mean, and are they necessary?

PMID- 28454742
TI  - Consequences of Epithelial Inflammasome Activation by Bacterial Pathogens.
AB  - Inflammasome signaling impinges on the activation of inflammatory caspases (i.e.,
      caspase-1 and caspase-4/5/11) and endows host cells with a sentinel system to
      sense microbial intrusion and thereby initiate appropriate immune responses.
      Lately, it has become evident that mammalian inflammasome-dependent responses to
      infection are not confined solely to cells of hematopoietic origin. Epithelial
      cells that line the body's mucosal surfaces use inflammasome signaling to sense
      and counteract pathogenic microorganisms that compromise barrier integrity. Many
      of the molecular mechanisms of epithelial inflammasome signaling remain
      unexplored. However, it now seems clear that epithelial inflammasome activation
      has a profound impact both on the infected cell itself and on its ability to
      communicate with other cell types of the mucosa. Here, we summarize current
      knowledge regarding the output of epithelial inflammasome activation during
      bacterial infection. Well-established downstream effects include epithelial cell
      death, release of soluble mediators, and subsequent recruitment of effector cell
      types, including NK cells, mast cells, and neutrophils, to sites of mucosal
      infection. We discuss the implications of recent findings for antibacterial
      defense in the mucosa and sketch out areas for future exploration.

PMID- 28454744
TI  - Imaging Probes and Modalities for the Study of Solute Carrier O (SLCO)-Transport
      Function In Vivo.
AB  - Transporters of the solute carrier O (SLCO) family, former organic anion
      transporting polypeptides, are now recognized as key players in pharmacokinetics.
      Imaging is increasingly regarded as a relevant method to elucidate and decipher
      the intrinsic role of SLCO in controlling drug disposition in plasma and tissues.
      Current research in this representative field of translational research is based
      on different imaging modalities including nuclear imaging, such as single-photon
      emission computed tomography or positron emission tomography, and magnetic
      resonance imaging. Imaging modalities can be compared in terms of sensitivity,
      quantitative properties, spatial resolution, variety of ligands, and radiation
      exposure. All these approaches rely on the use of SLCO substrates that are
      detected using corresponding modalities. The present review aims at reporting and
      comparing the imaging probes that have been proposed to study SLCO-transport
      function, in terms of in vitro specificity, in vivo behavior, and clinical
      validation.

PMID- 28454743
TI  - Amyloid beta-Sheet Secondary Structure Identified in UV-Induced Cataracts of
      Porcine Lenses using 2D IR Spectroscopy.
AB  - Cataracts are formed by the aggregation of crystallin proteins in the eye lens.
      Many in vitro studies have established that crystallin proteins precipitate into
      aggregates that contain amyloid fibers when denatured, but there is little
      evidence that ex vivo cataracts contain amyloid. In this study, we collect two
      dimensional infrared (2D IR) spectra on tissue slices of porcine eye lenses. As
      shown in control experiments on in vitro alphaB- and gammaD-crystallin, 2D IR
      spectroscopy can identify the highly ordered beta-sheets typical of amyloid
      secondary structure even if the fibers themselves are too short to be resolved
      with TEM. In ex vivo experiments of acid-treated tissues, characteristic 2D IR
      features are observed and fibers >50nm in length are resolved by transmission
      electron microscopy (TEM), consistent with amyloid fibers. In UV-irradiated lens
      tissues, fibers are not observed with TEM, but highly ordered beta-sheets of
      amyloid secondary structure is identified from the 2D IR spectra. The
      characteristic 2D IR features of amyloid beta-sheet secondary structure are
      created by as few as four or five strands and so identify amyloid secondary
      structure even if the aggregates themselves are too small to be resolved with
      TEM. We discuss these findings in the context of the chaperone system of the
      lens, which we hypothesize sequesters small aggregates, thereby preventing long
      fibers from forming. This study expands the scope of heterodyned 2D IR
      spectroscopy to tissues. The results provide a link between in vitro and ex vivo
      studies and support the hypothesis that cataracts are an amyloid disease.

PMID- 28454746
TI  - Involvement of Proton-Coupled Organic Cation Antiporter in Varenicline Transport
      at Blood-Brain Barrier of Rats and in Human Brain Capillary Endothelial Cells.
AB  - Varenicline is a selective partial alpha4beta2 nicotinic acetylcholine receptor
      agonist, which is used to help achieve smoking cessation. Here, we investigated
      varenicline transport at the blood-brain barrier by means of in vivo
      microdialysis, in situ brain perfusion, and brain efflux index measurements in
      rats, and in vitro uptake studies in human brain capillary endothelial cells.
      Microdialysis demonstrated that varenicline is actively transported from blood to
      brain in rats. Blood-to-brain uptake transport of varenicline, as measured by the
      in situ brain perfusion technique, was strongly inhibited by diphenhydramine, a
      potent inhibitor of proton-coupled organic cation (H+/OC) antiporter. However,
      brain efflux index study showed that brain-to-blood efflux transport of
      varenicline was not inhibited by diphenhydramine. In human brain capillary
      endothelial cells, varenicline was taken up time- and concentration-dependently.
      The uptake was dependent on an oppositely directed proton gradient, but was
      independent of extracellular sodium and membrane potential. The uptake was
      inhibited by a metabolic inhibitor, and by substrates of H+/OC antiporter, but
      not by substrates or inhibitors of OCTs, OCTNs, PMAT, and MATE1, which are known
      organic cation transporters. The present results suggest that the H+/OC
      antiporter contributes predominantly to varenicline uptake at the blood-brain
      barrier.

PMID- 28454748
TI  - Myomectomy at the Time of Caesarean Section.

PMID- 28454747
TI  - SGLT1-Mediated Transport in Caco-2 Cells Is Highly Dependent on Cell Bank Origin.
AB  - The human colon adenocarcinoma (Caco-2) cell line is a well-established in vitro
      model for studying transport phenomena for prediction of intestinal nutrient and
      drug absorption. However, substances depending on transporters such predictions
      are complicated due to variable transporter expression and limited knowledge
      about transporter function during multiple cell passaging and cell thawings. In
      the case of sodium glucose transporter 1 (SGLT1), a key transporter of oral
      absorption of d-glucose, one reason for compromised prediction could be
      inadequate expression of SGLT1 in Caco-2 cells and thereby limited sensitivity in
      the determination of SGLT1-mediated permeability (PSGLT1). Here, the objective is
      to characterize and compare SGLT1-mediated uptake in Caco-2 cells obtained from
      different cell banks. SGLT1-mediated uptake of the standard SGLT1 substrate,
      methyl-alpha-d-glucopyranoside, in Caco-2 cells was shown to be highly dependent
      on cell bank origin. The most robust and reliable SGLT1 functionality was
      identified in Caco-2 cells from Deutsche Sammlung fur Mikroorganismen und
      Zellkulturen (DSMZ), whereas cells from the American Type Culture Collection and
      European Collection of Authenticated Cell Cultures have lower SGLT1 transport
      activity. Transepithelial PSGLT1 across Caco-2 cells from DSMZ showed that PSGLT1
      likely accounts for approximately 97% of absorptive methyl-alpha-d
      glucopyranoside Papp(a-b). In conclusion, Caco-2 cells from DSMZ provide a robust
      in vitro model for studying SGLT1-mediated uptake and transport-over multiple
      cell passages and independent cell stock thawings.

PMID- 28454745
TI  - Retina-to-Blood Transport of 1-Methyl-4-Phenylpyridinium Involves Carrier
      Mediated Process at the Blood-Retinal Barrier.
AB  - 1-Methyl-4-phenylpyridinium (MPP+) transport at the blood-retinal barrier (BRB)
      was investigated. The retinal uptake index estimated for [3H]MPP+ was similar to
      that of [3H]d-mannitol, and was insensitive to unlabeled MPP+, suggesting no
      positive evidence to support the involvement of carrier-mediated transport in the
      blood-to-retina transport of MPP+ at the BRB. A microdialysis investigation
      showed that the concentration of [3H]MPP+ in the vitreous humor decreased in a
      biexponential manner, and the rate constant for [3H]MPP+ elimination during the
      terminal phase was greater than that of [14C]d-mannitol. The inhibition study of
      [3H]MPP+ elimination showed its substrate specificity, suggesting that the retina
      to-blood transport of MPP+ at the BRB involves a carrier-mediated process. The in
      vitro study with model cells showed the concentration-dependent transport of
      MPP+, supporting carrier-mediated MPP+ transport at the inner and outer BRB, and
      suggested membrane potential-sensitive and Na+-, Cl--, and pH-insensitive MPP+
      transport at the BRB. In the in vitro inhibition study, the transport of [3H]MPP+
      was significantly inhibited by organic cations, and further reverse transcription
      PCR analysis and knockdown study suggested that the retina-to-blood transport of
      MPP+ at the BRB is carried out by an unknown transporter of which transport
      function is similar to plasma membrane monoamine transporter (PMAT/SLC29A4).

PMID- 28454749
TI  - ?

PMID- 28454750
TI  - Management of Women with Short Cervix.

PMID- 28454751
TI  - ?

PMID- 28454752
TI  - Excerpts from the World Medical Literature.

PMID- 28454753
TI  - ?

PMID- 28454754
TI  - Independent Scientists Provide Guidance for the Future of Cervical Cancer
      Screening.

PMID- 28454755
TI  - Pregnancy Outcomes of Women Admitted to a Tertiary Care Centre with Short Cervix.
AB  - OBJECTIVE: Our aim was to characterize the management and outcome of women
      admitted to a tertiary high-risk obstetrics unit with a short cervix (<=25 mm),
      measured on transvaginal ultrasound (TVS), and to determine the latency period
      from diagnosis to delivery. METHODS: A retrospective chart review of women
      admitted to the High Risk Obstetrics Unit at Sunnybrook Health Sciences Centre
      between 2005-2011 with an ultrasound-identified short cervix was done. RESULTS: A
      total of 110 women admitted for a short cervix between 2005-2011 (N = 56
      singletons; N = 54 twin gestations) met the inclusion criteria. The mean latency
      to delivery was 62.6 days; mean GA at delivery was 33.9 weeks. Following 7 and 14
      days of admission, 5.5% and 11.8% of women had delivered, respectively. Preterm
      birth occurred in 70% of all women. Cervical length was a significant factor in
      predicting latency among singletons, whereas the length of stay in hospital for
      activity restriction was not. CONCLUSIONS: Although many women with a short
      cervix delivered preterm, only a small proportion delivered within 2 weeks of
      admission. Although it is not clear whether inpatient management improves the
      pregnancy outcome, these findings have implications for both patient care and
      health resources.

PMID- 28454756
TI  - Pregnancy of Unknown Location: A Survey-Based Evaluation of When and Why
      Physicians Intervene?
AB  - INTRODUCTION: Management of pregnancies of unknown location (PUL) is a complex
      challenging clinical situation with possibilities for pitfalls. Obstetricians and
      gynaecologists of varied levels of training and experience from Canada and the
      Nordic countries were questioned about their approach when faced with PUL.
      METHOD: A 13-item web-based questionnaire was used to evaluate physicians'
      behaviors by surveying their management of a PUL encountered at different levels
      of human chorionic gonadotropin (hCG). They were queried regarding the level of
      hCG at which they would take management action in an asymptomatic PUL, in a given
      scenario. RESULTS: Three hundred fifty three questionnaires were completed
      resulting in a response rate, representing completeness of the survey, of 78.6%.
      Three distinct hCG thresholds, at which intervention to interrupt a PUL would be
      considered, dominated the responses. Thirty seven percent of physicians would
      intervene at hCG levels between 1000-3000 IU, 22% selected the 4000-6000 IU
      range, and 13% would only intervene if the hCG level exceeded 10 000 IU. These
      ranges were similar across different levels of clinical experience. In addition
      to hCG values, a patient's desire to keep the pregnancy, the development of new
      symptoms, and the expected gestational age were the other principal factors
      influencing the decision to intervene. CONCLUSION: There appears to be little
      consensus regarding the hCG threshold at which medical intervention should be
      initiated in an asymptomatic pregnancy of unknown location and further studies to
      justify earlier or later intervention are needed to determine the appropriate
      time for intervention.

PMID- 28454757
TI  - No. 343-Routine Non-invasive Prenatal Prediction of Fetal RHD Genotype in Canada:
      The Time is Here.
AB  - : The optimal management of the D-negative pregnant woman is now based on the non
      invasive antenatal prediction of fetal D-blood group by cell-free DNA (cfDNA) in
      maternal plasma, with targeted prophylaxis for women carrying RHD-positive
      fetuses. This provides the optimal care for D-negative pregnant women and has
      been adopted as the standard approach in a growing number of countries around the
      world. This paper is the result of a consensus meeting of the Canadian National
      Rh Working Group, an interdisciplinary group formed to review the current status
      of fetal RHD genotyping based on cfDNA in Canada. The group, in collaboration
      with the SOGC Genetics committee, reviewed the benefits and challenges of
      implementing RHD genotyping with targeted prophylaxis in the context of the
      existing routine antenatal anti D prophylaxis program in Canada. The following
      summary statements and recommendations are based on this review. SUMMARY
      STATEMENTS: RECOMMENDATIONS.

PMID- 28454758
TI  - ?
AB  - Actuellement, la meilleure facon de prendre en charge les femmes enceintes Rh
      negatives consiste a predire la presence ou l'absence de l'antigene D chez le
      foetus au moyen d'un test non invasif analysant l'ADN acellulaire (ADNa) dans le
      plasma maternel, et a administrer une prophylaxie a celles dont l'enfant est RHD
      positif. Cette approche, prise pour norme dans un nombre croissant de pays,
      assure aux femmes enceintes Rh negatives des soins optimaux. La presente
      directive est le fruit d'une reunion de consensus du groupe de travail national
      sur le facteur Rh du Canada, un groupe interdisciplinaire forme pour examiner la
      situation nationale actuelle du genotypage RHD foetal effectue sur l'ADNa. En
      collaboration avec le Comite de genetique de la SOGC, le groupe s'est penche sur
      les avantages et les difficultes associes au genotypage RHD combine a une
      prophylaxie ciblee dans le contexte du programme de prophylaxie antenatale anti-D
      de routine canadien existant. De ce travail ont emerge les declarations sommaires
      et recommandations suivantes. DeCLARATIONS SOMMAIRES: RECOMMANDATIONS.

PMID- 28454759
TI  - Pattern and consequences of cardiologic medications management for patients with
      elevated troponin I upon admission into an intensive care unit not linked to type
      1 acute myocardial infarction: A prospective observational cohort study.
AB  - OBJECTIVES: No recommendations are currently available to help the clinician with
      the pharmacological management of intensive care unit (ICU) patients with
      elevated cardiac troponin (cTn) not linked to type 1 AMI. The aim of this study
      was to evaluate the pattern of cardiologic medications for patients with elevated
      cTnI in ICU not link to type 1 AMI and their effects on in-hospital mortality.
      MATERIAL AND METHODS: A prospective observational cohort study conducted in two
      ICU units. Patients with increased plasma concentration of cTnI at admission not
      linked to type 1 AMI were consecutively included. RESULTS: One hundred and ninety
      of the 835 patients admitted (23%) had an increased plasma concentration of cTnI
      not related to type 1 AMI. Antiplatelet therapy (AT) and statin were prescribed
      in 56 (29.5%) and 50 (26.3%) of patients, respectively. Others cardiologic
      medications were prescribed in less than 5% of all cases and were considered as
      contraindicated in more than 50% of cases. Antiplatelet therapy was the only
      cardiologic treatment associated with reduction of in-hospital mortality
      following uni- and multivariate analysis. The death rate was 23% and 40% in these
      patients treated with and without AT, respectively (aOR=0.39 [95% CI: 0.15
      0.97]). CONCLUSIONS: Statin and AT were frequently prescribed to patients with a
      cTnI elevation not linked to type 1 AMI. This study suggests that AT in patients
      with an increased plasma concentration of cTnI, not related to type 1 AMI in ICU,
      could reduce in-hospital mortality.

PMID- 28454760
TI  - Tropism and virulence of Cutibacterium (formerly Propionibacterium) acnes
      involved in implant-associated infection.
AB  - The recognition of the pathogenicity of Cutibacterium acnes in implant-associated
      infection is not always obvious. In this paper, we aimed to distinguish
      pathogenic and non-pathogenic C. acnes isolates. To reach this goal, we
      investigated the clonal complex (CC) of a large collection of C. acnes clinical
      isolates through Multi-Locus Sequence Typing (MLST), we established a
      Caenorhabditis elegans model to assess C. acnes virulence and we investigated the
      presence of virulence factors in our collection. Ours results showed that CC36
      and CC53 C. acnes isolates were more frequently observed in prosthetic joint
      infections (PJI) than CC18 and CC28 C. acnes isolates (p = 0.021). The C. elegans
      model developed here showed two distinct virulence groups of C. acnes (p < 0.05).
      These groups were not correlated to CC or clinical origin. Whole genome
      sequencing allowed us to identify a putative gene linked to low virulent strains.
      In conclusion, MLST remains a good method to screen pathogenic C. acnes isolates
      according to their clinical context but mechanisms of C. acnes virulence need to
      be assess thought transcriptomic analysis to investigate regulatory process.

PMID- 28454761
TI  - Bio-effect-monitoring of long-term thermal wastes on the oyster, Crassostrea
      gigas, using heat shock proteins.
AB  - We bio-monitored the stress of oyster, Crassostrea gigas, for possible long term
      effects of thermal waste from a power plant. The expression level of its heat
      shock proteins (HSPs) was measured by real time-reverse transcript PCR along with
      their density and growth in the field. Oyster size varied in a distance dependent
      pattern. Physics modeling for evaluation of spreading of the thermal effluent
      revealed that station A is affected by the thermal effluents abundance, and the
      size of C. gigas showed a negative relationship with distance to the power plant.
      The abundance and size of C. gigas were smallest at station A, which was closest
      to the thermal effluent outlet. The kinetics of changes in the hsp70 and hsp90
      mRNA levels in the mantle of C. gigas were also investigated. Regardless of the
      higher expression level of hsp70 mRNA than hsp90, both hsp70 and hsp90 mRNA
      levels were significantly higher at station A. The expression levels decreased
      inversely with distance from the thermal effluent outlet, with expression of
      hsp70 mRNA at station A being approximately 7-fold higher than at station B and
      15-fold higher than at station C. Similarly, expression of hsp90 mRNA at station
      A was approximately 14-fold higher than at station B and 22-fold higher than at
      station C. The present findings provide new insights on biological correlation
      among the growth of individuals and population size and the molecular index in C.
      gigas following thermal effects.

PMID- 28454762
TI  - Accumulation of endocrine disrupting chemicals in the liver of Diplodus sargus
      sargus in Torre Guaceto Natural Reserve.
AB  - Studies on the quality of marine environments in Italy have traditionally
      favoured heavily impacted areas, such as harbours and industrial areas, while
      there are few investigations aimed at the evaluation of the presence of organic
      pollutants in the areas of marine reserve. The aim of this study was to determine
      endocrine-disrupting compounds (EDCs) in the liver of white seabreams (Diplodus
      sargus sargus) from the Natural Reserve of Torre Guaceto, Italy. Among EDCs,
      alkyl-phenols 2,6-DTBP, 2,4-DTBP, OP, and BPA were identified and quantified. The
      mean concentration of 2,6-DTBP, 2,4-DTBP, OP, and BPA were 2.2, 2.0, 1.2 and
      3.6ng/g of liver, respectively, confirming the occurrence and transfer of these
      organic pollutants in the food web of marine organisms in marine reserves.

PMID- 28454763
TI  - Sources and distribution of polycyclic aromatic hydrocarbons (PAHs) and organic
      matter in surface sediments of an estuary under petroleum activity influence,
      Todos os Santos Bay, Brazil.
AB  - The present study evaluated the origin and distribution of polycyclic aromatic
      hydrocarbons (PAHs) and the organic matter (OM) in the surface sediment of the
      Sao Paulo River estuary, Todos os Santos Bay (TSB), Brazil. The samples were
      collected in the rainy (CP1) and the dry (CP2) seasons. We analyzed the 16 PAHs
      from the United States Environmental Protection Agency (US EPA) priority
      pollutant list, total organic carbon (TOC), total nitrogen (N), and stable carbon
      isotope (delta13C). The total concentration of PAHs ranged from 11.45+/-1.28 to
      1825.35+/-107.96ngg-1, while TOC ranged from 3.8 to 27.7gkg-1. CP1 showed the
      highest concentrations for all parameters. The delta13C ratio indicated
      terrigenous OM (-23.81 to -26.630/00). The TOC/N ratio (C/N) indicated
      transitional OM (12.32 to 24.39), in addition to the continental origin. The
      diagnostic ratios of PAHs origin revealed only pyrolytic source, although close
      to areas with a history of petroleum contamination.

PMID- 28454764
TI  - Ribosomal proteins as documents of the transition from unstructured
      (poly)peptides to folded proteins.
AB  - For the most part, contemporary proteins can be traced back to a basic set of a
      few thousand domain prototypes, many of which were already established in the
      Last Universal Common Ancestor of life on Earth, around 3.5 billion years ago.
      The origin of these domain prototypes, however, remains poorly understood. One
      hypothesis posits that they arose from an ancestral set of peptides, which acted
      as cofactors of RNA-mediated catalysis and replication. Initially, these peptides
      were entirely dependent on the RNA scaffold for their structure, but as their
      complexity increased, they became able to form structures by excluding water
      through hydrophobic contacts, making them independent of the RNA scaffold. Their
      ability to fold was thus an emergent property of peptide-RNA coevolution. The
      ribosome is the main survivor of this primordial RNA world and offers an
      excellent model system for retracing the steps that led to the folded proteins of
      today, due to its very slow rate of change. Close to the peptidyl transferase
      center, which is the oldest part of the ribosome, proteins are extended and
      largely devoid of secondary structure; further from the center, their secondary
      structure content increases and supersecondary topologies become common, although
      the proteins still largely lack a hydrophobic core; at the ribosomal periphery,
      supersecondary structures coalesce around hydrophobic cores, forming folds that
      resemble those seen in proteins of the cytosol. Collectively, ribosomal proteins
      thus offer a window onto the time when proteins were acquiring the ability to
      fold.

PMID- 28454765
TI  - Black-blood T2* mapping with delay alternating with nutation for tailored
      excitation.
AB  - PURPOSE: To develop a black-blood T2* mapping method using a Delay Alternating
      with Nutation for Tailored Excitation (DANTE) preparation combined with a multi
      echo gradient echo (GRE) readout (DANTE-GRE). MATERIALS AND METHODS: Simulations
      of the Bloch equation for DANTE-GRE were performed to optimize sequence
      parameters. After optimization, the sequence was applied to a phantom scan and to
      neck and lower extremity scans conducted on 12 volunteers at 3T using DANTE-GRE,
      Motion-Sensitized Driven Equilibrium (MSDE)-GRE, and multi-echo GRE. T2* values
      were measured using an offset model. Statistical analyses were conducted to
      compare the T2* values between the three sequences. RESULTS: Simulation results
      showed that blood suppression can be achieved with various DANTE parameter
      adjustments. T2* maps acquired by DANTE-GRE were consistent and comparable to
      those acquired with multi-echo GRE in phantom experiments. In the in vivo
      experiments, DANTE-GRE was more comparable to multi-echo GRE than MSDE-GRE
      regarding the measurement of muscle T2* values. CONCLUSION: Due to its high
      signal intensity retention and effective blood signal suppression, DANTE-GRE
      allows for robust and accurate T2* quantification, superior to that of MSDE-GRE,
      while overcoming blood flow artifacts associated with traditional multi-echo GRE.

PMID- 28454766
TI  - Mixture effects of azole fungicides on the adrenal gland in a broad dose range.
AB  - Consumers are exposed to low concentrations of a variety of pesticide residues in
      or on food. Some of them might interfere with the endocrine system. While each
      individual active substance has been extensively tested for toxicity and safety,
      potential combination effects possibly resulting from combined exposure to
      different pesticides have seldomly been tested so far, especially in vivo. Since
      the adrenal gland is a key endocrine organ, we investigated if and how substances
      of a group of fungicides presumed to interfere with the biosynthesis of steroid
      hormones affect this organ when applied individually and in combination in a
      broad dose range. A 28-day feeding study was conducted in Wistar rats by using
      three (tri)azole fungicides considered to potentially affect the endocrine system
      (cyproconazole, epoxiconazole and prochloraz) individually at five dose levels,
      ranging from 0.9ppm to 2400ppm, and in combination at three dose levels. The
      parameters analysed included classical toxicology (pathology, histopathology,
      clinical chemistry) and molecular toxicology endpoints (gene expression arrays
      and quantitative real time PCR e.g. of Star, HSD3beta, Cyp11a1, Cyp11b1, Cyp11b2,
      Cyp 21, ApoE), as well as hormone analysis. A dose-dependent decrease in the
      adrenal gland weight of rats treated with epoxiconazole alone, which was
      accompanied by an atrophy of the adrenal gland as well as by an increase in the
      serum cholesterol level and which only became statistically significant at the
      top dose levels, was observed. These effects were attenuated in the combination
      experiments, although the same epoxiconazole concentration was used.

PMID- 28454767
TI  - Emergence of tissue shape changes from collective cell behaviours.
AB  - Anyone watching a movie of embryonic development immediately appreciates the
      importance of morphogenetic movements and cell flows that reshape tissue. Dynamic
      tissue shape changes are genetically choreographed, but their execution is
      essentially a mechanical event. How the interplay between genetics and tissue
      mechanics controls tissue shape is a fundamental question. Key insights into this
      problem have emerged from studies in different model organisms as well as in
      cultured epithelia. These studies have revealed how gene expression patterns can
      generate patterns of planar cell polarity that orient cellular force generation
      and give rise to anisotropic mechanical properties of cells and tissues. These
      can autonomously bias the rate and orientation of cellular events such as cell
      divisions, extrusions, neighbor exchanges and shape changes that drive
      morphogenesis. However recent studies also highlight how autonomously controlled
      cell dynamics lead to tissue-wide stress patterns framed by mechanical
      constraints such as cellular connections to extracellular matrices. These stress
      patterns themselves can orient the cell behaviours underlying morphogenesis. As a
      result of this interplay, tissue shape emerges in a mechanical process that
      tightly couples mechanics and genetics.

PMID- 28454768
TI  - Association of hospital contact precaution policies with emergency department
      admission time.
AB  - BACKGROUND: Contact precautions are a widely accepted strategy to reduce in
      hospital transmission of meticillin-resistant Staphylococcus aureus (MRSA) and
      vancomycin-resistant enterococci (VRE). However, these practices may have
      unintended deleterious effects on patients. AIM: To evaluate the effect of a
      modification in hospital-wide contact precaution practices on emergency
      department (ED) admission times. METHODS: During the study period, the hospital
      changed its contact precaution policy from requiring contact precautions for all
      patients with a history of MRSA or VRE to only those who presented with clinical
      conditions likely to contaminate the environment with pathogens. An interrupted
      time series analysis of ED admission times for adults for one year preceding and
      one year following this change was performed at a two-campus hospital. The main
      outcome was admission time, defined as time from decision to admit to arrival in
      an inpatient bed, for patients with MRSA or VRE compared with all other patients.
      The in-hospital MRSA and VRE acquisition rates were evaluated over the same
      period and have been published previously. FINDINGS: At one campus, admission
      time decreased immediately by 161min for MRSA patients (P=0.008) and 135min for
      VRE patients (P=0.003), and both continued to decrease over the duration of the
      study. There was no significant change in admission time at the second campus.
      CONCLUSIONS: Modifying contact precaution requirements for MRSA and VRE may be
      associated with improved ED admission time without significantly altering in
      hospital MRSA and VRE acquisition.

PMID- 28454769
TI  - Long-lasting outbreak due to CTX-M-15-producing Klebsiella pneumoniae ST336 in a
      rehabilitation ward: report and literature review.
AB  - BACKGROUND: Whereas Klebsiella species are the most frequently occurring agents
      in nosocomial outbreaks due to multidrug-resistant Gram-negative organisms, very
      few outbreaks have been reported from rehabilitation wards. AIM: To describe a
      long-lasting outbreak due to extended-spectrum beta-lactamase-producing (ESBL)
      Klebsiella pneumoniae in a rehabilitation ward. METHODS: ESBL K. pneumoniae from
      all in- and outpatients whose specimens were tested at a tertiary care university
      hospital between 2007 and 2012 were typed by pulsed-field gel electrophoresis and
      selected isolates were submitted to multi-locus sequence typing and ESBL
      genotyping. Outbreak characteristics and infection control interventions were
      summarized. The literature was searched for K. pneumoniae-related outbreaks in
      rehabilitation wards. FINDINGS: ESBL K. pneumoniae was detected in 69 out of 2478
      K. pneumoniae-positive patients (2.8%) during the study period. Eight related
      outbreak clones from 35 patients, 25 of whom were in the rehabilitation ward,
      produced CTX-M-15 and belonged to ST336. The outbreak lasted for more than three
      years and was controlled by sequentially increasing measures culminating in
      review of all patient-related care, compulsory educational meetings for
      personnel, profession-specific guidelines and educational flyers for patients.
      CONCLUSION: Half of ESBL K. pneumoniae-positive patients identified over six
      years at a tertiary care university hospital harboured related clones, and more
      than a third were hospitalized in a rehabilitation ward. Rehabilitation wards
      pose particular challenges for infection control because of patient dependency
      and an environment that encourages socializing. They are, however, rarely
      involved in K. pneumoniae-related outbreaks.

PMID- 28454770
TI  - From the Editor.

PMID- 28454772
TI  - Effects of client-centered multimodal treatment on impairment, function, and
      satisfaction of people with thumb carpometacarpal osteoarthritis.
AB  - STUDY DESIGN: Prepost design. INTRODUCTION: Previous research regarding the non
      surgical treatment of thumb carpometacarpal joint osteoarthritis has been based
      on protocol driven research designs that primarily examined impairment level
      changes. Exploration is therefore needed to determine the benefits of
      individually prescribed orthoses, joint protection and assistive device education
      programs that are based on the activities the person needs to regularly perform.
      PURPOSE OF THE STUDY: The primary objective of this study was to examine the
      effect of client-centered multimodal treatment on activity, participation,
      impairment, and satisfaction of people with thumb carpometacarpal joint
      osteoarthritis. METHODS: A total of 60 participants completed the study that used
      a prepost design. The Canadian Occupational Performance Measure (COPM) was used
      to identify the participants' performance and satisfaction concerning their self
      identified occupational performance issues. Additional outcome measures that were
      used included the Disabilities of the Arm, Shoulder and Hand (DASH)
      questionnaire, total active range of motion (TAROM), lateral pinch strength, and
      the visual analog scale for pain. All participants completed a client-centered 6
      week program that consisted of the use of an orthosis, joint protection, and
      assistive device education as well as exercises. RESULTS: At 6 weeks after
      initiation of treatment, pain, pinch strength, TAROM, the DASH questionnaire and
      the performance and satisfaction scales of the COPM had significantly improved.
      The changes in pain, TAROM, and the performance and satisfaction scales of the
      COPM were all greater than the minimal clinically important difference. The
      changes in pain and lateral pinch strength were significantly associated with
      changes in activity and participation. DISCUSSION: This study demonstrated that a
      multimodal, client-centered treatment approach resulted in statistically and
      clinically significant improvement in pain, TAROM and performance and
      satisfaction as measured by the COPM. The improvement in pain was associated with
      the participants' improved ability to engage in activities assessed by the DASH.
      CONCLUSIONS: Our results support the use of client-centered treatment strategies
      that are targeted to control pain during meaningful activity when working with
      patients with thumb carpometacarpal joint osteoarthritis therapists. LEVEL OF
      EVIDENCE: 4.

PMID- 28454771
TI  - Next-generation superparamagnetic iron oxide nanoparticles for cancer
      theranostics.
AB  - Superparamagnetic iron oxide (SPIO) nanoparticles have been intensively studied
      for the development of contrast agents in MRI. First-generation SPIO
      nanoparticles had diagnostic capabilities only, whereas a new generation of SPIO
      nanoparticle has multifunctional characteristics for combined therapeutic and
      diagnostic applications. These theranostic nanoparticles hold great potential for
      image-guided cancer therapies. In particular, polymer-coated theranostic SPIO
      nanoparticles have enjoyed increasing attention as a result of good
      biocompatibility, biodegradability and versatile functionality endowed by
      polymeric matrices. This review provides an overview of recently developed
      polymer-coated multifunctional SPIO nanoparticles for cancer theranostics and
      discusses current challenges and future perspectives.

PMID- 28454773
TI  - Efficacy of 3 therapeutic taping configurations for children with brachial plexus
      birth palsy.
AB  - STUDY DESIGN: Cross-sectional clinical measurement study. INTRODUCTION: Scapular
      winging is a frequent complaint among children with brachial plexus birth palsy
      (BPBP). Therapeutic taping for scapular stabilization has been reported to
      decrease scapular winging. PURPOSE OF THE STUDY: This study aimed to determine
      which therapeutic taping construct was most effective for children with BPBP.
      METHODS: Twenty-eight children with BPBP participated in motion capture
      assessment with 4 taping conditions: (1) no tape, (2) facilitation of rhomboid
      major and rhomboid minor, (3) facilitation of middle and lower trapezius, and (4)
      facilitation of rhomboid major, rhomboid minor, and middle and lower trapezius
      (combination of both 2 and 3, referred to as combined taping). The participants
      held their arms in 4 positions: (1) neutral with arms by their sides, (2) hand to
      mouth, (3) hand to belly, and (4) maximum crossbody adduction (CBA). The
      scapulothoracic, glenohumeral and humerothoracic (HT) joint angles and joint
      angular displacements were compared using multivariate analyses of variance with
      Bonferroni corrections. RESULTS: Scapular winging was significantly decreased in
      both the trapezius and combined taping conditions in all positions compared with
      no tape. Rhomboids taping had no effect. Combined taping reduced HT CBA in the
      CBA position. CONCLUSIONS: Rhomboid taping cannot be recommended for treatment of
      children with BPBP. Both trapezius and combined taping approaches reduced
      scapular winging, but HT CBA was limited with combined taping. Therefore,
      therapeutic taping of middle and lower trapezius was the most effective
      configuration for scapular stabilization in children with BPBP. Resting posture
      improved, but performance of the positions was not significantly improved. LEVEL
      OF EVIDENCE: Level II.

PMID- 28454775
TI  - Iluminated by foreign letters - Strategies for site-specific cyclopropene
      modification of large functional RNAs via in vitro transcription.
AB  - The synthesis of sequence-specifically modified long RNA molecules, which cannot
      entirely be prepared via solid phase synthesis methods is experimentally
      challenging. We are using a new approach based on an expanded genetic alphabet
      preparing site-specifically modified RNA molecules via standard in vitro
      transcription. In this report, the site-specific labeling of functional RNAs, in
      particular ribozymes and a long non-coding RNA with cyclopropene moieties, is
      presented. We provide detailed instructions for RNA labeling via in vitro
      transcription and include required analytical methods to verify production and
      identity of the transcript. We further present post-transcriptional inverse
      electron demand Diels-Alder cycloaddition reactions on the cyclopropene-modified
      sequences and discuss applications of the genetic alphabet expansion
      transcription for in vitro preparation of labeled functional RNAs with complex
      foldings. In detail, the glmS and CPEB3 ribozymes were site-specifically
      decorated with methyl cyclopropene moieties using the unnatural TPT3CP
      triphosphate and were proven to be still functional. In addition, the
      structurally complex A region of the Xist lncRNA (401nt) was site-specifically
      modified with methyl cyclopropene and detected by fluorescence after
      cycloaddition reaction with a tetrazine-BODIPY conjugate.

PMID- 28454774
TI  - Identification of N6-methyladenosine reader proteins.
AB  - The reversible N6-methyladenosine (m6A) modification of eukaryotic messenger RNAs
      (mRNAs) is a widespread regulatory mechanism that impacts every step in the mRNA
      life cycle. The effect of m6A on mRNA fate depends on the binding of "m6A reader"
      proteins - RNA binding proteins that specifically bind to RNAs containing m6A.
      Here, we describe an RNA pull-down method that can be used to identify novel m6A
      reader proteins starting from a known m6A-modified site in cellular or viral RNA.
      We further describe how a combination of immunoprecipitation-based sequencing
      methods can be used to identify m6A-modified sites bound by an m6A reader protein
      on a transcriptome-wide level. The discovery of new m6A reader proteins and their
      m6A-modified targets would provide further insight into the mechanisms and
      functions of m6A in the cell.

PMID- 28454776
TI  - Functional association prediction by community profiling.
AB  - Recent years have witnessed unprecedented accumulation of DNA sequences and
      therefore protein sequences (predicted from DNA sequences), due to the advances
      of sequencing technology. One of the major sources of the hypothetical proteins
      is the metagenomics research. Current annotation of metagenomes (collections of
      short metagenomic sequences or assemblies) relies on similarity searches against
      known gene/protein families, based on which functional profiles of microbial
      communities can be built. This practice, however, leaves out the hypothetical
      proteins, which may outnumber the known proteins for many microbial communities.
      On the other hand, we may ask: what can we gain from the large number of
      metagenomes made available by the metagenomic studies, for the annotation of
      metagenomic sequences as well as functional annotation of hypothetical proteins
      in general? Here we propose a community profiling approach for predicting
      functional associations between proteins: two proteins are predicted to be
      associated if they share similar presence and absence profiles (called community
      profiles) across microbial communities. Community profiling is conceptually
      similar to the phylogenetic profiling approach to functional prediction, however
      with fundamental differences. We tested different profile construction methods,
      the selection of reference metagenomes, and correlation metrics, among others, to
      optimize the performance of this new approach. We demonstrated that the community
      profiling approach alone slightly outperforms the phylogenetic profiling approach
      for associating proteins in species that are well represented by sequenced
      genomes, and combining phylogenetic and community profiling further improves
      (though only marginally) the prediction of functional association. Further we
      showed that community profiling method significantly outperforms phylogenetic
      profiling, revealing more functional associations, when applied to a more
      recently sequenced bacterial genome.

PMID- 28454777
TI  - Identification of causative organism in cardiac implantable electronic device
      infections.
AB  - BACKGROUND: The causative organism in cardiovascular implantable electronic
      device (CIED) infection is usually diagnosed with the cultures from blood,
      removed leads, and/or infected pocket material. The cultured organism, however,
      is sometimes different among these samples. METHODS: Two hundred sixty patients
      with CIED infection, who underwent lead extraction between April 2005 and
      December 2014, were analyzed. More than two blood culture sets, all the extracted
      leads, and swab culture of the pocket were sent to the laboratory for culture.
      Among the patients all of whose microbiological examinations were available, we
      analyzed the causative organism defined as the species detected in at least two
      different sites. RESULTS: All the culture results were available in the 208
      patients, showing 69 systemic infections (including 30 cases of infectious
      endocarditis) and 139 local infections. Blood culture, lead culture, and swab
      culture were positive in 57 (27%), 169 (81%), and 152 (73%), respectively.
      Staphylococcus aureus [37% including methicillin-resistant S. aureus (MRSA)
      (12%)] and coagulase-negative staphylococci (CoNS, 36%) were the most common
      causative organism, followed by non-staphylococci (23%), and poly-microbial
      infection (4%). The detection of S. aureus from pocket or removed leads rendered
      higher predictive value of a causative organism than that of CoNS. The detection
      of Gram-negative bacteria, fungi, and mycobacteria indicated that it was most
      likely a causative organism. Gram-positive bacteria excluding Staphylococcus,
      such as Corynebacterium spp., tended to coexist as a benign organism.
      CONCLUSIONS: The causative organism is mostly S. aureus and CoNS. Detection of S.
      aureus or Gram-negative bacteria means that it is more likely a causative
      organism.

PMID- 28454779
TI  - Congenital extensor tendon dislocation causing pseudotriggering of the little
      finger.
AB  - The main complaints in extensor tendon dislocations are pain, swelling, sense of
      discomfort, snapping and difficulty in writing and forceful flexion. However,
      congenital extensor tendon subluxations may present with triggering of the
      fingers due to tendon dislocations. Unnecessary A1 pulley release may be
      performed for pseudotriggerring with unsuccessful results. Here, we report an
      unusual case of congenital extensor tendon subluxation of multiple digits with
      triggering of the left little finger and aim to attract notice to
      pseudotriggering of the digits due to tendon dislocations. An extensor hood
      reconstruction performed by an extensor digitorum communis tendon slip which is
      passed beneath the deep intermetacarpal ligament is a successful choice of
      treatment for these patients.

PMID- 28454778
TI  - Decision analysis to identify the ideal treatment for adult spinal deformity:
      What is the impact of complications on treatment outcomes?
AB  - OBJECTIVE: The aim of this study was to analyze the impact of treatment
      complications on outcomes in adult spinal deformity (ASD) using a decision
      analysis (DA) model. METHODS: The study included 535 ASD patients (371 with non
      surgical (NS) and 164 with surgical (S) treatment) from an international
      multicentre database of ASD patients. DA was structured in two main steps; 1)
      Baseline analysis (Assessing the probabilities of outcomes, Assessing the values
      of preference -utilities-, Combining information on probability and utility and
      assigning the quality adjusted life expectancy (QALE) for each treatment) and 2)
      Sensitivity analysis. Complications were analyzed as life threatening (LT) and
      nonlife threatening (NLT) and their probabilities were calculated from the
      database as well as a thorough literature review. Outcomes were analyzed as
      improvement, no change and deterioration. Death/complete paralysis was considered
      as a separate category. RESULTS: All 535 patients were analyzed in regard to
      complications. Overall, there were 78 NLT and 12 LT complications and 3
      death/paralysis. Surgical treatment offered significantly higher chances of
      clinical improvement but also was significantly more prone to complications
      (31.7% vs. 11.1%, p < 0.001). CONCLUSION: Surgical treatment of ASD is more
      likely to cause complications compared to NS treatment. On the other hand,
      surgery has been shown to provide a higher likelihood of improvement in HRQoL
      scores. So, the decision on the type of treatment in ASD needs to take both
      chances of improvement and burden associated with S or NS treatments and better
      be arrived by the active participation of patients and physicians equipped with
      the present information. LEVEL OF EVIDENCE: Level II, Decision analysis.

PMID- 28454780
TI  - A comparison of rat degloving injury models.
AB  - OBJECTIVE: Two different rat models for degloving injury were described in the
      literature. Our aim in this study is to compare these rat models to determine
      which one is more reliable and reproducible. METHODS: We surgically induced
      degloving injury on tails and left hindlimbs of Wistar albino rats (n = 8), and
      sutured the avulsed tissues back in their original positions after a waiting
      period. We observed the changes in the avulsed flaps every other day for 10 days.
      At the end of follow-up period we evaluated the lesions in avulsed flaps by
      macroscopic measurement of necrosis and histological ulcer scoring using the
      National Pressure Ulcer Advisory Panel (NPUAP) Scale. RESULTS: The average length
      of necrosis in avulsed tail flaps was 28.42 +/- 3.04 mm, whereas there was no
      necrosis in avulsed hindlimb flaps (p < 0.05). The average ulcer score of the
      lesions in tail and left hindlimb were 3.42 +/- 0.78, and 1.28 +/- 0.48,
      respectively (p < 0.05). Despite the lack of visible necrosis TUNEL staining
      revealed an increased amount of apoptotic cells in avulsed hindlimb flaps.
      Literature review revealed a significant variability in previous studies in terms
      of the amount of necrosis observed in tail degloving injury model. CONCLUSION:
      Tail degloving injury model proved to be a more reliable animal model for
      degloving injuries. However, standardization of the magnitude of degloving force
      is required to decrease the variability of necrosis observed in the literature.

PMID- 28454781
TI  - Incredible position of broken sliding dynamic hip screw implant in the medial of
      thigh.
AB  - We report a case with implant failure after nailing of an unstable
      pertrochanteric fracture with dynamic hip screw. The patient presented with a
      medial sided thigh pain at 5 years after the surgery. Plain radiographs showed
      nonunion of the fracture with distant migration of assembled hip screw and side
      plate to the subcutaneous area of the inner thigh.

PMID- 28454782
TI  - Radiation dose and risks to fetus from nuclear medicine procedures.
AB  - This article discusses issues regarding administration of radiopharmaceuticals to
      pregnant women. Standardized dose estimates and possible biological effects on
      the unborn child are presented. Current and future mathematical models (phantoms)
      are discussed. Standardized dose estimates for pregnant women at several stages
      of gestation based on the current generation of phantoms are given. Issues
      related to administration of radioiodines, particularly 131I-NaI, are presented.
      Iodine concentrates in the fetal thyroid and therefore can give very high doses,
      even resulting in complete destruction of the fetal thyroid. Strategies for
      preventing unwanted administrations of radiopharmaceuticals to these patients,
      and for strategies for mitigating radiation doses, should an unwanted
      administration occur, are discussed.

PMID- 28454783
TI  - Lack of genotoxicity in vivo for food color additive Tartrazine.
AB  - Tartrazine is approved as a food color additive internationally with INS number
      102, in the United States as food color subject to batch certification "Food,
      Drug, and Cosmetic" (FD&C) Yellow No. 5, and in Europe as food color additive
      with E number 102. In their evaluation of the color (2013), the European Food
      Safety Authority (EFSA) expressed concerns of potential genotoxicity, based
      primarily on one genotoxicity study that was not conducted according to
      Guidelines. The present in vivo genotoxicity study was conducted according to
      OECD Guidelines in response to EFSA's request for additional data. The animal
      species and strain, and the tissues examined were selected specifically to
      address the previously reported findings. The results of this study show clear
      absence of genotoxic activity for Tartrazine, in the bone marrow micronucleus
      assay and the Comet assay in the liver, stomach, and colon. These data addressed
      EFSA's concerns for genotoxicity. The Joint WHO/FAO Committee on Food Additives
      (JECFA) (2016) also reviewed these data and concluded that there is no
      genotoxicity concern for Tartrazine. Negative findings in parallel genotoxicity
      studies on Allura Red AC and Ponceau 4R (published separately) are consistent
      with lack of genotoxicity for azo dyes used as food colors.

PMID- 28454784
TI  - Evaluation of cytotoxic, apoptotic, mutagenic, and chemopreventive activities of
      semi-synthetic esters of gallic acid.
AB  - Gallic acid and its derivatives are phenolic compounds widely used as food
      supplements in the form of capsules, liquid extracts, and ointments owing to
      their good antioxidant properties. Besides, these compounds are potent inhibitors
      of fungi, bacteria, and some viruses and possess strong antiproliferative and
      chemopreventive activities. However, gallic acid derivatives are also known to
      exert harmful effects like mutagenicity and cytotoxicity. The present study aimed
      to understand and explore the toxicological risks of these compounds. For this, a
      series of alkyl gallates with side chains varying from five to eight carbons
      (pentyl, hexyl, heptyl, and octyl gallates) were evaluated for their cytotoxic
      and pro-apoptotic potential. In addition, the genotoxic effects of alkyl gallates
      were measured in HepG2 cells using the single cell gel electrophoresis
      (SCGE)/comet assay and the cytokinesis-blocked micronucleus (CBMN) test. In both
      the tests, the substances did not induce any significant differences when
      compared to the control group. In addition, alkyl gallates exhibited a
      chemopreventive effect, thereby considerably reducing the mutagenicity caused by
      H2O2. In conclusion, our results suggest that alkyl gallates are non-genotoxic,
      non-mutagenic, and pro-apoptotic agents, which may serve as suitable and
      promising candidates for preventing chemically-induced chromosomal damage.

PMID- 28454785
TI  - RIFM fragrance ingredient safety assessment, 1-cyclohexylethyl butyrate, CAS
      Registry Number 63449-88-7.

PMID- 28454786
TI  - RIFM fragrance ingredient safety assessment, 3,7-dimethyl-1-octanyl acetate, CAS
      Registry Number 20780-49-8.

PMID- 28454787
TI  - RIFM fragrance ingredient safety assessment, 3-methylbutyl 2-methylpropanoate,
      CAS Registry Number 2050-01-3.

PMID- 28454788
TI  - Good or bad patient: Labels that affect the patient's ability to make decisions.

PMID- 28454790
TI  - The impact of hepatitis B carrier on cardiac troponin I in 100-km ultramarathon
      runners.
AB  - BACKGROUND: Prolonged endurance exercise is known to cause elevation of cardiac
      troponin I (cTnI). Previous studies have reported the correlation of several
      factors with exercise-induced cTnI release. However, the investigation of the
      predictors for elevated cTnI and postrace kinetics of cTnI after ultramarathon
      running is lacking, especially in an Oriental population. METHODS: Twenty-six
      participants, including eight hepatitis B virus carrier (HBVc) runners, who
      finished a 100-km ultramarathon in Taiwan were enrolled. For each participant,
      blood samples were collected 1 week before the race, as well as immediately and
      24 hours after the finish. RESULTS: The results showed that 19 runners (73.1%)
      had postrace elevated cTnI levels and eight (30.8%) had elevated cTnI values
      lasting more than 24 hours after the run. A multiple linear regression analysis
      demonstrated that the HBV status was a factor related to the high level of cTnI
      after 24 hours of running (beta=0.03, p=0.08). The recovery of plasma cTnI levels
      was delayed in ultramarathon runners with latent HBV infection. Among HBVc
      runners, multiple linear regression analyses showed age (beta=-0.01), previous
      running experience (beta=-0.06), training distance (beta=0.37), and 4 hours of
      running distance (beta=-0.04) as significant predictors of higher postrace cTnI
      levels. CONCLUSION: For most athletes, cTnI values significantly increased
      immediately following the race in the absence of adverse clinical sequelae, and
      HBVc runners had higher and prolonged cTnI levels. While several factors are
      identified for such HBV effects, the specific causes need further elucidation.

PMID- 28454789
TI  - CXCR5-Overexpressing Mesenchymal Stromal Cells Exhibit Enhanced Homing and Can
      Decrease Contact Hypersensitivity.
AB  - Mesenchymal stromal cells (MSCs) can modulate inflammation and contribute to
      tissue regeneration and, thus, have emerged as a promising option for cell-based
      therapy. However, the ability of MSCs to migrate to injured tissues still needs
      to be improved. In this study, we investigated whether genetically engineered
      MSCs could exhibit increased migratory properties and improved therapeutic
      efficacy. Using a mouse model of contact hypersensitivity (CHS), chemokine gene
      expression screening revealed that CXCL13 changed most significantly in injured
      tissue. Unfortunately, MSCs hardly express the corresponding receptor, CXCR5.
      Thus, CXCR5-overexpressing MSCs (MSCCXCR5) were generated that retained their
      abilities of proliferation, differentiation, and immunomodulation. Furthermore,
      MSCCXCR5 showed significantly increased migrating ability toward CXCL13.
      Importantly, systemic infusion of MSCCXCR5 dramatically suppressed CHS in mice,
      as evidenced by decreased levels of inflammatory cell infiltration and pro
      inflammatory cytokine production. Numerous MSCCXCR5 migrated into inflamed ears,
      localized with T cells, inhibited T cell proliferation, promoted T cell
      apoptosis, and suppressed the production of T cell-derived pro-inflammatory
      factors. Collectively, these findings demonstrate that CXCR5 overexpression
      increases the ability of MSCs to respond to migratory stimuli and highly
      intensifies their immunomodulatory effects in vivo. This strategy for enhancing
      targeted stem/progenitor cell homing may improve the efficacy of MSC-based
      therapies.

PMID- 28454791
TI  - Transesophageal echocardiography for incremental value of Amplatezer cribriform
      septal occluder for percutaneous transcatheter closure of complex septal defects:
      Case series.
AB  - BACKGROUND: The anatomy of septal defects can be complex and morphologically
      unpredictable. Balloon sizing of such defects may not be feasible, and an
      appropriately sized commercial occluder may not be available. Therefore,
      percutaneous transcatheter closure of such defects can be challenging because of
      an increased risk of complications. In this study, we have described the efficacy
      and safety of transcatheter closure of complex septal defects using Amplatzer
      cribriform occluder devices, assessed by real time three-dimensional (RT 3D)
      color Doppler transesophageal echocardiography (TEE). METHODS AND RESULTS: Four
      complex septal defects were involved in this investigation: (1) reimplanted
      multiple atrial septal defects (ASD) with one device embolization; (2)
      postinfarction ventricular septal defect; (3) long tunnel patent foramen ovale;
      and (4) postoperative residual ASD. All patients underwent percutaneous
      transcatheter interventions due to the high risk of surgical complications, and
      one of the three available cribriform ASD device sizes (18 mm, 25 mm, or 35 mm)
      was implanted. Perioperative RT 3D TEE combined with fluoroscopy was used for
      monitoring during the procedure. All defects were successfully occluded by
      cribriform septal occluder devices using the transcatheter technique. CONCLUSION:
      Our patients with complex septal defects were successfully treated by
      transcatheter closure using an Amplazter cribriform septal occluder device with
      careful planning based on patient presentation and close interdisciplinary
      collaboration. RT 3D color Doppler TEE provided precise information for the
      selection of the appropriate occluder device and facilitated the procedure by
      guiding the catheter through the often challenging patient anatomy.

PMID- 28454792
TI  - Baseline characteristics of patients enrolled in the Exenatide Study of
      Cardiovascular Event Lowering (EXSCEL).
AB  - BACKGROUND: EXSCEL is a randomized, double-blind, placebo-controlled trial
      examining the effect of exenatide once-weekly (EQW) versus placebo on time to the
      primary composite outcome (cardiovascular death, nonfatal myocardial infarction
      or nonfatal stroke) in patients with type 2 diabetes mellitus (DM) and a wide
      range of cardiovascular (CV) risk. METHODS: Patients were enrolled at 688 sites
      in 35 countries. We describe their baseline characteristics according to prior CV
      event status and compare patients with those enrolled in prior glucagon-like
      peptide-1 receptor agonist (GLP-1RA) outcomes trials. RESULTS: Of a total of
      14,752 participants randomized between June 2010 and September 2015, 6,788
      (46.0%) patients were enrolled in Europe; 3,708 (25.1%), North America; 2,727
      (18.5%), Latin America; and 1,529 (10.4%), Asia Pacific. Overall, 73% had at
      least one prior CV event (70% coronary artery disease, 24% peripheral arterial
      disease, 22% cerebrovascular disease). The median (IQR) age was 63 years (56,
      69), 38% were female, median baseline HbA1c was 8.0% (7.3, 8.9) and 16% had a
      prior history of heart failure. Those without a prior CV event were younger with
      a shorter duration of diabetes and better renal function than those with at least
      one prior CV event. Compared with prior GLP-1RA trials, EXSCEL has a larger
      percentage of patients without a prior CV event and a notable percentage who were
      taking a dipeptidyl peptidase-4 inhibitor at baseline (15%). CONCLUSIONS: EXSCEL
      is one of the largest global GLP-1RA trials, evaluating the safety and efficacy
      of EQW with a broad patient population that may extend generalizability compared
      to prior GLP-1RA trials (ClinicalTrials.gov number, NCT01144338).

PMID- 28454793
TI  - Determinants of operator radiation exposure during percutaneous coronary
      procedures.
AB  - BACKGROUND: Radiation exposure is an important issue for interventional
      cardiologists that is often underevaluated. Our aim was to evaluate determinants
      of operator radiation exposure during percutaneous coronary procedures. METHODS:
      The RADIANT (NCT01974453) is a prospective, single-center observational study
      involving 4 expert operators and 2 fellows performing percutaneous coronary
      procedures. The operator radiation dose was evaluated using dedicated electronic
      dosimeters in 2,028 procedures: 1,897 transradial access (TRA; 1,120 right and
      777 left TRA) and 131 transfemoral access (TFA). RESULTS: In the whole
      population, operator radiation dose at the thorax did not differ between TFA
      (9MUSv [interquartile range 5-18MUSv]) and TRA (9MUSv [4-21MUSv]), but after
      propensity score matching analysis, TFA showed lower dose (9MUSv [5-18MUSv])
      compared with TRA (17MUSv [9-28MUSv], P<.001). In the whole transradial group,
      left TRA (5MUSv [2-12MUSv]) was associated with significant lower operator dose
      compared with right TRA (13MUSv [6-26MUSv], P<.001).The use of adjunctive
      protective pelvic drapes was significantly associated with lower radiation doses
      compared with procedures performed without drapes (P<.001). Among the operators,
      an inverse relation between height and dose was observed. Finally, left
      projections and the use of angiographic systems not dedicated for coronary and
      high frame rates were all associated with a significant higher operator radiation
      exposure. CONCLUSIONS: In a high-volume center for transradial procedures, TFA is
      associated with lower operator radiation dose compared with TRA. The use of
      adjunctive anti-rx drapes seems a valuable tool to reduce the higher operator
      radiation exposure associated with TRA.

PMID- 28454794
TI  - Reduced duration of dual antiplatelet therapy using an improved drug-eluting
      stent for percutaneous coronary intervention of the left main artery in a real
      world, all-comer population: Rationale and study design of the prospective
      randomized multicenter IDEAL-LM trial.
AB  - BACKGROUND: Continuous improvements in stent technology make percutaneous
      coronary intervention (PCI) a potential alternative to surgery in selected
      patients with unprotected left main coronary artery (uLMCA) disease. The optimal
      duration of dual antiplatelet therapy (DAPT) in these patients remains
      undetermined, and in addition, new stent designs using a bioabsorbable polymer
      might allow shorter duration of DAPT. STUDY DESIGN: IDEAL-LM is a prospective,
      randomized, multicenter study that will enroll 818 patients undergoing uLMCA PCI.
      Patients will be randomized in a 1:1 fashion to intravascular ultrasound-guided
      PCI with the novel everolimus-eluting platinum-chromium Synergy stent with a
      biodegradable polymer (Boston Scientific, Natick, MA) followed by 4 months of
      DAPT or the everolimus-eluting cobalt-chromium Xience stent (Abbott Vascular,
      Santa Clara, CA) followed by 12 months of DAPT. The total follow-up period will
      be 5 years. A subset of 100 patients will undergo optical coherence tomography at
      3 months. END POINTS: The primary end point will be major adverse cardiovascular
      events (composite of all-cause mortality, myocardial infarction, and ischemia
      driven target vessel revascularization) at 2 years. Secondary end points will
      consist of the individual components of the primary end point, procedural
      success, a device-oriented composite end point, stent thrombosis as per Academic
      Research Consortium criteria, and bleeding as per Bleeding Academic Research
      Consortium criteria. SUMMARY: IDEAL-LM is designed to assess the safety and
      efficacy of the novel Synergy stent followed by 4 months of DAPT vs the Xience
      stent followed by 12 months of DAPT in patients undergoing uLMCA PCI. The study
      will provide novel insights regarding optimal treatment strategy for patients
      undergoing PCI of uLMCA disease (www.clinicaltrials.gov, NCT 02303717).

PMID- 28454795
TI  - Rationale and design of the Japan-USA harmonized assessment by randomized,
      multicenter study of OrbusNEich's combo StEnt (Japan-USA HARMONEE): Assessment of
      a novel DES platform for percutaneous coronary revascularization in patients with
      ischemic coronary disease and non-ST-elevation acute coronary syndrome.
AB  - Tissue trauma associated with stent implantation continues to generate early
      thrombosis rates of 0.9% to 1.3% for both bare-metal and drug-eluting stent
      platforms. The Combo sirolimus-eluting stent combines an abluminal, bioabsorbable
      polymer with a luminal CD34+ antibody designed to capture endothelial progenitor
      cells. This article describes the design and methods of the HARMONEE trial
      (NCT02073565), which represents the first randomized controlled trial of the
      Combo design against a best-in-class contemporary everolimus-eluting stent. Up to
      50 sites in Japan and the United States will enroll 286 subjects (271 evaluable)
      in each of 2 arms, for a total sample size of 572 subjects (542 evaluable). The
      statistical plan includes both superiority to imputed bare-metal stent control
      and noninferiority to everolimus-eluting stent on a primary clinical end point of
      target vessel failure at 1 year. In addition, fractional flow reserve assessment
      to evaluate the physiology of target vessels in the entire population will
      augment the end point definition of ischemia-driven target vessel
      revascularization. Finally, key safety considerations will be evaluated with a
      subpopulation with optical coherence tomography imaging for strut coverage, late
      strut malapposition, and plaque volume, as well as serial human antimurine
      antibody assessments. As the first international prospective randomized coronary
      intervention study under the "Harmonization by Doing" program, this study
      represents a unique collaboration between regulators and investigators in Japan
      and the United States.

PMID- 28454796
TI  - Atrial fibrillation detected by continuous electrocardiographic monitoring using
      implantable loop recorder to prevent stroke in individuals at risk (the LOOP
      study): Rationale and design of a large randomized controlled trial.
AB  - : Atrial fibrillation (AF) increases the rate of stroke 5-fold, and AF-related
      strokes have a poorer prognosis compared with non-AF-related strokes. Atrial
      fibrillation and stroke constitute an intensifying challenge, and health care
      organizations are calling for awareness on the topic. Previous studies have
      demonstrated that AF is often asymptomatic and consequently undiagnosed. The
      implantable loop recorder (ILR) allows for continuous, long-term
      electrocardiographic monitoring with daily transmission of arrhythmia
      information, potentially leading to improvement in AF detection and stroke
      prevention. METHODS: The LOOP study is an investigator-initiated, randomized
      controlled trial with 6,000 participants randomized 3:1 to a control group or to
      receive an ILR with continuous electrocardiographic monitoring. Participants are
      identified from Danish registries and are eligible for inclusion if 70years or
      older and previously diagnosed as having at least one of the following
      conditions: hypertension, diabetes mellitus, heart failure, or previous stroke.
      Exclusion criteria include history of AF and current oral anticoagulation
      treatment. When an AF episode lasting >=6minutes is detected, oral
      anticoagulation will be initiated according to guidelines. Expected follow-up is
      4years. The primary end point is time to stroke or systemic embolism, whereas
      secondary end points include time to AF diagnosis and death. CONCLUSION: The LOOP
      study will evaluate health benefits and cost-effectiveness of ILR as a screening
      tool for AF to prevent stroke in patients at risk. Secondary objectives include
      identification of risk factors for the development of AF and characterization of
      arrhythmias in the population. The trial holds the potential to influence the
      future of stroke prevention.

PMID- 28454797
TI  - Toward evidence-based diagnosis of myocarditis in children and adolescents:
      Rationale, design, and first baseline data of MYKKE, a multicenter registry and
      study platform.
AB  - : The aim of this registry is to provide data on age-related clinical features of
      suspected myocarditis and to create a study platform allowing for deriving
      diagnostic criteria and, at a later stage, testing therapeutic interventions in
      patients with myocarditis. STUDY DESIGN AND RESULTS: After an initial 6-month
      pilot phase, MYKKE was opened in June 2014 as a prospective multicenter registry
      for patients from pediatric heart centers, university hospitals, and community
      hospitals with pediatric cardiology wards in Germany. Inclusion criteria
      consisted of age<18 years and hospitalization for suspected myocarditis as
      leading diagnosis at the discretion of the treating physician. By December 31,
      2015, fifteen centers across Germany were actively participating and had enrolled
      149 patients. Baseline data reveal 2 age peaks (<2 years, >12 years), show higher
      proportions of males, and document a high prevalence of severe disease courses in
      pediatric patients with suspected myocarditis. Severe clinical courses and early
      adverse events were more prevalent in younger patients and were related to
      severely impaired leftventricular ejection fraction at initial presentation.
      SUMMARY: MYKKE represents a multicenter registry and research platform for
      children and adolescents with suspected myocarditis that achieve steady
      recruitment and generate a wide range of real-world data on clinical course,
      diagnostic workup, and treatment of this group of patients. The baseline data
      reveal the presence of 2 age peaks and provide important insights into the
      severity of disease in children with suspected myocarditis. In the future, MYKKE
      might facilitate interventional substudies by providing an established
      collaborating network using common diagnostic approaches.

PMID- 28454798
TI  - The Design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric
      Hypertrophic Cardiomyopathy (VANISH) Trial.
AB  - : Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations,
      resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and
      increased risk of sudden cardiac death and heart failure. Studies in mouse models
      of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor
      blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human
      studies using ARBs for HCM have targeted heterogeneous adult cohorts with well
      established disease. The VANISH trial is testing the safety and feasibility of
      disease-modifying therapy with an ARB in genotyped HCM patients with early
      disease. METHODS: A randomized, placebo-controlled, double-blind clinical trial
      is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM
      and no/minimal symptoms, or those with early phenotypic manifestations but no
      LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily
      (depending on age and weight) or placebo. The primary endpoint is a composite of
      9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac
      morphology, and function. Total z-scores reflecting change from baseline to final
      visits will be compared between treatment groups. Secondary endpoints will assess
      the impact of treatment on mutation carriers without LVH, and analyze the
      influence of age, sex, and genotype. CONCLUSIONS: The VANISH trial is testing a
      new strategy of disease modification for treating sarcomere mutation carriers
      with early HCM, and those at risk for its development. In addition, further
      insight into disease mechanisms, response to therapy, and phenotypic evolution
      will be gained.

PMID- 28454799
TI  - Long-term electrocardiographic safety monitoring in clinical drug development: A
      report from the Cardiac Safety Research Consortium.
AB  - This white paper, prepared by members of the Cardiac Safety Research Consortium
      (CSRC), discusses important issues regarding scientific and clinical aspects of
      long-term electrocardiographic safety monitoring during clinical drug
      development. To promote multistakeholder discussion of this topic, a Cardiac
      Safety Research Consortium-sponsored Think Tank was held on 2 December 2015 at
      the American College of Cardiology's Heart House in Washington, DC. The goal of
      the Think Tank was to explore how and under what circumstances new and evolving
      ambulatory monitoring technologies could be used to improve and streamline drug
      development. This paper provides a detailed summary of discussions at the Think
      Tank: it does not represent regulatory guidance.

PMID- 28454800
TI  - Rationale and Design of Family-Based Approach in a Minority Community Integrating
      Systems-Biology for Promotion of Health (FAMILIA).
AB  - BACKGROUND: The 2020 American Heart Association Impact Goal aims to improve
      cardiovascular health of all Americans by 20% while reducing deaths from
      cardiovascular disease and stroke by 20%. A large step toward this goal would be
      to better understand and take advantage of the significant intersection between
      behavior and biology across the entire life-span. In the proposed FAMILIA
      studies, we aim to directly address this major knowledge and clinical health gap
      by implementing an integrated family-centric health promotion intervention and
      focusing on the intersection of environment and behavior, while understanding the
      genetic and biologic basis of cardiovascular disease. METHODS: We plan to recruit
      600 preschool children and their 600 parents or caregivers from 12-15 Head Start
      schools in Harlem, NY, and perform a 2:1 (2 intervention/1 control) cluster
      randomization of the schools. The preschool children will receive our intensive
      37-hour educational program as the intervention for 4 months. For the adults,
      those in the "intervention" group will be randomly assigned to 1 of 2
      intervention programs: an "individual-focused" or "peer-to-peer based." The
      primary outcome in children will be a composite score of knowledge (K), attitudes
      (A), habits (H), related to body mass index Z score (B), exercise (E), and
      alimentation (A) (KAH-BEA), using questionnaires and anthropometric measurements.
      For adults, the primary outcome will be a composite score for behaviors/outcomes
      related to blood pressure, exercise, weight, alimentation (diet) and tobacco
      (smoking; Fuster-BEWAT score). Saliva will be collected from the children for SNP
      genotyping, and blood will be collected from adults for RNA sequencing to
      identify network models and predictors of primary prevention outcomes.
      CONCLUSION: The FAMILIA studies seek to demonstrate that targeting a younger age
      group (3-5 years) and using a family-based approach may be a critical strategy in
      promoting cardiovascular health across the life-span.

PMID- 28454801
TI  - Randomized Evaluation of the Effects of Anacetrapib through Lipid-modification
      (REVEAL)-A large-scale, randomized, placebo-controlled trial of the clinical
      effects of anacetrapib among people with established vascular disease: Trial
      design, recruitment, and baseline characteristics.
AB  - : Patients with prior vascular disease remain at high risk for cardiovascular
      events despite intensive statin-based treatment. Inhibition of cholesteryl ester
      transfer protein by anacetrapib reduces low-density lipoprotein (LDL) cholesterol
      by around 25% to 40% and more than doubles high-density lipoprotein (HDL)
      cholesterol. However, it is not known if these apparently favorable lipid changes
      translate into reductions in cardiovascular events. METHODS: The REVEAL study is
      a randomized, double-blind, placebo-controlled clinical trial that is assessing
      the efficacy and safety of adding anacetrapib to effective LDL-lowering treatment
      with atorvastatin for an average of at least 4years among patients with
      preexisting atherosclerotic vascular disease. The primary assessment is an
      intention-to-treat comparison among all randomized participants of the effects of
      allocation to anacetrapib on major coronary events (defined as the occurrence of
      coronary death, myocardial infarction, or coronary revascularization). RESULTS:
      Between August 2011 and October 2013, 30,449 individuals in Europe, North
      America, and China were randomized to receive anacetrapib 100mg daily or matching
      placebo. Mean (SD) age was 67 (8) years, 84% were male, 88% had a history of
      coronary heart disease, 22% had cerebrovascular disease, and 37% had diabetes
      mellitus. At the randomization visit (after at least 8weeks on a protocol-defined
      atorvastatin regimen), mean plasma LDL cholesterol was 61 (15) mg/dL and HDL
      cholesterol was 40 (10) mg/dL. INTERPRETATION: The REVEAL trial will provide a
      robust evaluation of the clinical efficacy and safety of adding anacetrapib to an
      effective statin regimen. Results are anticipated in 2017.

PMID- 28454802
TI  - Association of measured platelet reactivity with changes in P2Y12 receptor
      inhibitor therapy and outcomes after myocardial infarction: Insights into routine
      clinical practice from the TReatment with ADP receptor iNhibitorS: Longitudinal
      Assessment of Treatment Patterns and Events after Acute Coronary Syndrome
      (TRANSLATE-ACS) study.
AB  - BACKGROUND: Little is known about the use of platelet function testing to guide
      choice of P2Y12 receptor inhibitor therapy in routine clinical practice. METHODS:
      We studied 671 myocardial infarction (MI) patients treated with percutaneous
      coronary intervention in the TRANSLATE-ACS Registry who had VerifyNow platelet
      function testing performed while on clopidogrel treatment during their index
      hospitalization (April 2010-October 2012). RESULTS: High platelet reactivity
      (>208 platelet reactivity units [PRU]) was present in 261 (38.9%) patients.
      Clopidogrel was switched in-hospital to prasugrel in 80 (30.7%) patients with
      high platelet reactivity and 18 (4.4%) patients with therapeutic platelet
      reactivity (<=208 PRU). Among high platelet reactivity patients, switch to
      prasugrel was associated with lower major adverse cardiovascular events (death,
      MI, stroke, or unplanned revascularization) at 1year (10.0% vs 22.7%, P=.02;
      adjusted odds ratio [OR] 0.39, 95% CI 0.18-0.85, P=.02) and no significant
      difference in Bleeding Academic Research Consortium type 2 or higher bleeding
      (23.8% vs 22.1%, P=.77; adjusted OR 0.91, 95% CI 0.48-1.7, P=.77) compared with
      patients continued on clopidogrel. No significant differences in major adverse
      cardiovascular event (22.2% vs 12.8%, P=.25; adjusted OR 1.8, 95% CI 0.47-7.3,
      P=.38) or bleeding (22.2% vs 19.4%, P=.77; adjusted OR 1.3, 95% CI 0.27-6.8,
      P=.72) were observed among therapeutic platelet reactivity patients between
      switching and continuation on clopidogrel. CONCLUSIONS: Only one-third of
      percutaneous coronary intervention-treated MI patients with high on-clopidogrel
      platelet reactivity were switched to a more potent P2Y12 receptor inhibitor.
      Intensification of antiplatelet therapy was associated with lower risk of
      ischemic events at 1year among HPR patients.

PMID- 28454803
TI  - Recurrent MI and stroke post-acute coronary syndrome: Which is the lesser evil?

PMID- 28454804
TI  - Differential occurrence, profile, and impact of first recurrent cardiovascular
      events after an acute coronary syndrome.
AB  - OBJECTIVE: Acute coronary syndrome (ACS) trials typically use a composite primary
      outcome (myocardial infarction [MI], stroke, or cardiovascular death), but
      differential patient characteristics, timing, and consequences associated with
      individual component end points as first events have not been well studied. We
      compared patient characteristics and prognostic significance associated with
      first cardiovascular events in the post-ACS setting for initially stabilized
      patients. METHODS: We combined patient-level data from 4 trials of post-ACS
      antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to
      characterize the timing of and characteristics associated with first
      cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at
      7 days after index ACS presentation was used to focus on spontaneous,
      postdischarge events that were not confounded by in-hospital procedural
      complications. Using a competing risk framework, we tested for differential
      associations between prespecified covariates and the occurrence of nonfatal
      stroke vs MI as the first event, and we examined subsequent events after the
      first nonfatal event. RESULTS: Among 46,694 patients with a median follow-up of
      358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in
      4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n =
      477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior
      stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic
      blood pressure were associated with a significantly greater risk of stroke vs MI,
      whereas prior percutaneous coronary intervention was associated with a greater
      risk of MI vs stroke. Second events occurred in 32% of those with a first
      nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32%
      of those with a first nonfatal MI at a median of 35 (5, 137) days after the first
      event. The most common second event was a recurrent MI among those with MI as the
      first event and cardiovascular death among those with stroke as the first event.
      CONCLUSIONS: Approximately 9% of patients experienced a first cardiovascular
      event in the post-ACS setting during a median follow-up of 1 year. Although the
      profile and prognostic implications of stroke vs MI as the first nonfatal event
      differ substantially, approximately one-third of these patients experienced a
      second event, typically soon after the first event. These findings have
      implications for improving post-ACS care and influencing the design of future
      cardiovascular trials.

PMID- 28454805
TI  - Managing subfertility in patients with heart disease: What are the choices?
AB  - More women with heart disease are reaching reproductive age and will want to
      embark upon pregnancy. Furthermore, many of these women are delaying pregnancy
      until later in life when they may be exposed to a greater number of complications
      from their heart disease. A relatively high proportion of these women will pursue
      fertility treatment to achieve a pregnancy; consequently, the management of
      subfertile couples where the woman (or man) has heart disease is of growing
      importance. In this review, we discuss how fertility investigations and treatment
      can impact a women with heart disease and how some of the potential complications
      can be minimized or avoided. We also consider surrogacy, which is an important
      option when pregnancy is contraindicated.

PMID- 28454806
TI  - Assessing MICRO-vascular resistances via IMR to predict outcome in STEMI patients
      with multivessel disease undergoing primary PCI (AMICRO): Rationale and design of
      a prospective multicenter clinical trial.
AB  - BACKGROUND: In STEMI patients treated with primary percutaneous coronary
      angioplasty (PPCI) the evaluation of coronary microcirculatory resistance index
      (IMR) predict the extent of microvascular damage and left ventricular (LV)
      remodeling. However, the impact of IMR on the clinical outcome after PPCI in
      patients with multivessel disease (MVD) remains unsettled. AIM: We designed a
      prospective multicenter controlled clinical trial to evaluate the prognostic
      value of IMR in terms of clinical outcome and left ventricular remodeling in
      STEMI patients with MVD undergoing PPCI. METHODS AND DESIGN: The study will
      involve 242 patients with MVD defines as the presence of at least a non-culprit
      lesion of >50% stenosis at index coronary angiography. Both fractional flow
      reserve (FFR) and IMR will be measured in the infarct-related artery (IRA) after
      successful PPCI. Measurements of FFR and IMR will be repeated in the IRA and
      performed in the non-culprit vessels at staged angiography. The non-culprit
      vessel lesions will be treated only in the presence of a FFR<0.75. A 2D
      echocardiographic evaluation of the left ventricular (LV) volumes and ejection
      fraction will be performed before hospital discharge and at 1-year follow-up. The
      primary end-point of the study will be the composite of cardiovascular death, re
      hospitalization for heart failure and resuscitation or appropriate ICD shock
      during 1-year of follow-up. Secondary end-points will be the impact of IMR in
      predicting LV remodeling during follow-up and correlations between IMR and ST
      segment resolution. Other secondary endpoints will be need for new
      revascularization, stent thrombosis and re-infarction of the non-culprit vessels
      territory. IMPLICATIONS: If IMR significantly correlates with differences in
      outcome and LV remodeling, it will emerge as a potential prognostic index after
      PPCI in patients with MVD.

PMID- 28454807
TI  - Clinical decision support for stroke prevention in atrial fibrillation (CDS-AF):
      Rationale and design of a cluster randomized trial in the primary care setting.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity, in
      particular stroke. Despite good evidence for the reduction of stroke risk with
      anticoagulant therapy, there remains a significant undertreatment. The main aim
      of the current study is to investigate whether a clinical decision support tool
      for stroke prevention (CDS) integrated in the electronic health record can
      improve adherence to guidelines for stroke prevention in patients with AF.
      METHODS: We will conduct a cluster randomized trial where 43 primary care clinics
      in the county of Ostergotland, Sweden (population 444,347), will be randomized to
      be part of the CDS intervention or serve as controls. The CDS will alert
      responsible physicians of patients with AF and increased risk for thromboembolism
      according to the CHA2DS2VASc (Congestive heart failure, Hypertension, Age >= 74
      years, Diabetes mellitus, previous Stroke/TIA/thromboembolism, Vascular disease,
      Age 65-74 years, Sex category (i.e. female sex)) algorithm without anticoagulant
      therapy. The primary end point will be adherence to guidelines after 1 year.
      CONCLUSION: The present study will investigate whether a clinical decision
      support system integrated in an electronic health record can increase adherence
      to guidelines regarding anticoagulant therapy in patients with AF.

PMID- 28454808
TI  - An examination of the relationship between serum uric acid level, a clinical
      history of gout, and cardiovascular outcomes among patients with acute coronary
      syndrome.
AB  - BACKGROUND: Studies have suggested a relationship between higher baseline serum
      uric acid (sUA) levels and an elevated risk of subsequent ischemic cardiovascular
      outcomes among acute coronary syndrome (ACS) patients; this relationship may be
      modified by a clinical history of gout and has not been studied in large patient
      cohorts. We sought to understand the effect of sUA and gout on ACS outcomes.
      METHODS: Using PLATO and TRACER data on 27,959 ACS patients, we evaluated
      baseline sUA levels in relation to a composite of cardiovascular death,
      myocardial infarction (MI), or stroke. We assessed interaction terms to determine
      if a baseline clinical diagnosis of gout modified this putative relationship; 46%
      (n=12,882) had sUA levels elevated >6.0 mg/dL. RESULTS: Patients with elevated
      levels were more often male with a history of prior MI, diabetes, and heart
      failure compared with those with sUA <6.0 mg/dL. The unadjusted risk of the
      composite endpoint increased with corresponding elevations in sUA levels (per 1
      mg/dL increase) (HR=1.23 [95% CI: 1.20-1.26]) above the statistical inflection
      point of 5.0 mg/dL. After adjustment, the association between sUA level and the
      composite outcome remained significant (HR=1.07 [95% CI: 1.04-1.10]), and
      baseline gout did not modify this relationship. CONCLUSIONS: In patients with
      ACS, increasing levels of sUA are associated with an elevated risk of
      cardiovascular events, regardless of a clinical diagnosis of gout. Further
      investigation is warranted to determine the mechanism behind this relationship
      and to delineate whether sUA is an appropriate therapeutic target to reduce
      cardiovascular risk.

PMID- 28454809
TI  - Day vs night: Does time of presentation matter in acute heart failure? A
      secondary analysis from the RELAX-AHF trial.
AB  - BACKGROUND: Signs and symptoms of heart failure can occur at any time.
      Differences between acute heart failure (AHF) patients who present at nighttime
      vs daytime and their outcomes have not been well studied. Our objective was to
      determine if there are differences in baseline characteristics and clinical
      outcomes between AHF patients presenting during daytime vs nighttime hours within
      an international, clinical trial. METHODS: This is a post hoc analysis of the
      RELAX AHF trial, which randomized 1,161 AHF patients to serelaxin vs placebo,
      both in addition to usual AHF therapy. Prespecified end points of the primary
      trial were used: dyspnea, 60-day heart failure/renal failure rehospitalization or
      cardiovascular (CV) death, and 180-day CV death. Both unadjusted and adjusted
      analyses for outcomes stratified by daytime vs nighttime presentation were
      performed. RESULTS: Of the 1,161 RELAX-AHF patients, 775 (66.8%) patients
      presented during daytime and 386 (33.2%) at nighttime. Baseline characteristics
      were largely similar, although daytime patients were more likely to be male, have
      greater baseline body weight, have higher New York Heart Association class, have
      history of atrial fibrillation, and have more peripheral edema compared with
      nighttime patients. No differences in dyspnea relief or 60-day outcomes were
      observed. However, daytime presentation was associated with greater risk for 180
      day CV death after adjustment (hazard ratio 2.28, 95% CI 1.34-3.86; c statistic =
      0.82, 95% CI 0.78-0.86). CONCLUSION: In this secondary analysis of the RELAX-AHF
      trial, baseline characteristics suggest that daytime-presenting patients may have
      more gradual worsening of chronic HF. Patients with AHF who presented at night
      had less risk for 180-day CV death, but similar risk for 60-day CV death or
      rehospitalization and symptom improvement for patients who presented during the
      daytime.

PMID- 28454810
TI  - Time to achieving therapeutic international normalized ratio increases hospital
      length of stay after heart valve replacement surgery.
AB  - BACKGROUND: Achieving a therapeutic international normalized ratio (INR) before
      hospital discharge is an important inpatient goal for patients undergoing
      mechanical cardiac valve replacement (MCVR). The use of clinical algorithms has
      reduced the time to achieve therapeutic INR (TTI) with warfarin therapy. Whether
      TTI prolongs length of stay (LOS) is unknown. METHODS: Patients who underwent
      MCVR over a consecutive 42-month period were included. Clinical data were
      obtained from the Society of Thoracic Surgeons Adult Cardiac Surgery database and
      electronic medical records. Therapeutic INR was defined as per standard
      guidelines. Warfarin dose was prescribed using an inpatient pharmacy-managed
      algorithm and computer-based dosing tool. International normalized ratio
      trajectory, procedural needs, and drug interactions were included in warfarin
      dose determination. RESULTS: There were 708 patients who underwent MCVR, of which
      159 were excluded for reasons that would preclude or interrupt warfarin use.
      Among the remainder of 549 patients, the average LOS was 6.4days and mean TTI was
      3.5days. Landmark analysis showed that subjects in hospital on day 4 (n=542) who
      achieved therapeutic INR were more likely to be discharged by day 6 compared with
      those who did not achieve therapeutic INR (75% vs 59%, P<.001). Multivariable
      proportional hazards regression with TTI as a time-dependent effect showed a
      strong association with discharge (P=.0096, hazard ratio1.3) after adjustment for
      other significant clinical covariates. CONCLUSIONS: Time to achieve therapeutic
      INR is an independent predictor of LOS in patients requiring anticoagulation with
      warfarin after MCVR surgery. Alternative dosing and anticoagulation strategies
      will need to be adopted to reduce LOS in these patients.

PMID- 28454811
TI  - Compliance with guideline-directed therapy in diabetic patients admitted with
      acute coronary syndrome: Findings from the American Heart Association's Get With
      The Guidelines-Coronary Artery Disease (GWTG-CAD) program.
AB  - BACKGROUND: To evaluate and compare baseline characteristics, outcomes and
      compliance with guideline based therapy at discharge among diabetic and non
      diabetic patients admitted with acute coronary syndromes (ACS). METHODS AND
      RESULTS: Study population consisted of 151,270 patients admitted with ACS from
      2002 through 2008 at 411 sites participating in the American Heart Association's
      Get with the Guidelines (GWTG) program. Demographic variables, physical exam
      findings, laboratory data, left ventricular ejection fraction, length of stay, in
      hospital mortality and discharge medications were compared between diabetic and
      non-diabetic patients. Temporal trends in compliance with guidelines directed
      therapy were evaluated. Of 151,270 patients, 48,938 (32%) had diabetes. Overall,
      diabetic patients were significantly older and more likely non-white. They had
      significantly more hypertension, atherosclerotic disease, CKD, and LV dysfunction
      and were more likely to present as NSTEMI. They had longer hospital stay and
      higher hospital mortality than non-diabetic patients. Diabetic patients were less
      likely to get LDL checks (65% vs 70%) and less frequently prescribed statins (85%
      vs 89%), RAAS blockers for LV dysfunction (80% vs 84%) and dual-antiplatelet
      therapy (69% vs 74%). Diabetic patients were less likely to achieve BP goals
      before discharge (75% vs 82%). Fewer diabetic patients met first medical contact
      to PCI time for STEMI (44% vs 52%). Temporal trends, however, showed continued
      progressive improvement in most performance measures from 2002 to 2008 (all
      P<.001). CONCLUSIONS: These data from a large cohort of ACS patients demonstrate
      gaps in compliance with guidelines directed therapy in diabetic patients but also
      indicate significant and continued improvement in most performance measures over
      time. Concerted efforts are needed to continue this positive trend.

PMID- 28454812
TI  - Factors associated with rhythm control treatment decisions in patients with
      atrial fibrillation-Insights from the NCDR PINNACLE registry.
AB  - BACKGROUND: Decisions to use rhythm control in atrial fibrillation (AF) should
      generally be dictated by patient factors, such as quality of life, heart failure,
      and other comorbidities. Whether or not other factors affect decisions about the
      use of rhythm control, and catheter ablation in particular, is unknown. METHODS:
      A cohort of all patients diagnosed with nonvalvular AF were identified from the
      National Cardiovascular Data Registry's Practice Innovation and Clinical
      Excellence (PINNACLE) AF registry of US outpatient cardiology practices during
      the study period from May 1, 2008, to December 31, 2014. Overall and practice
      specific rates of rhythm control (cardioversion, antiarrhythmic drug therapy, or
      catheter ablation) were assessed. We assessed patient and practice factors
      associated with rhythm control and determined the relative contribution of
      patient, practice, and unmeasured practice factors with its use. RESULTS: Among
      511,958 PINNACLE AF patients, 22.3% were treated with rhythm control and 2.9%
      underwent catheter ablation. Significant practice variation in rhythm control was
      present (median rate of rhythm control across practices 22.8%, range 0.2%-62.9%).
      Significant patient factors associated with rhythm control therapy included white
      (vs nonwhite) race (odds ratio [OR] 2.43, P<.001), private (vs nonprivate)
      insurance (OR 1.04, P<.001), and whether a patient was seen by an
      electrophysiologist (OR 1.77, P<.001). In an analysis of the relative
      contribution of patient, practice, and unmeasured practice factors with rhythm
      control, the contribution of unmeasured practice factors (95% range OR 0.29-3.44)
      exceeded that of either patient (95% range OR 0.46-2.30) or practice (95% range
      OR 0.15-2.77) factors. CONCLUSIONS: One in 5 AF patients in the PINNACLE registry
      received rhythm control, and 1 in 50 received catheter ablation, suggesting that
      rhythm control may be underused. A variety of measured and unmeasured practice
      factors unrelated to patient characteristics play a disproportionate role in the
      use of rhythm control treatment decisions. Understanding the drivers of these
      decisions may identify inappropriate treatment variation and better inform
      optimal use of these therapies.

PMID- 28454813
TI  - Percutaneous revascularization in patients treated with thoracic radiation for
      cancer.
AB  - OBJECTIVES: To assess coronary revascularization outcomes in patients with
      previous thoracic radiation therapy (XRT). BACKGROUND: Previous chest radiation
      has been reported to adversely affect long term survival in patients with
      coronary disease treated with percutaneous coronary interventions (PCI). METHODS:
      Retrospective, single center cohort study of patients previously treated with
      thoracic radiation and PCI. Patients were propensity matched against control
      patients without radiation undergoing revascularization during the same time
      period. RESULTS: We identified 116 patients with radiation followed by PCI (XRT
      PCI group) and 408 controls. Acute procedural complications were similar between
      groups. There were no differences in all-cause and cardiac mortality between
      groups (all-cause mortality HR 1.31, P=.078; cardiac mortality 0.78, P=.49).
      CONCLUSION: Patients with prior thoracic radiation and coronary disease treated
      with PCI have similar procedural complications and long term mortality when
      compared to control subjects.

PMID- 28454814
TI  - beta-Blocker after acute myocardial infarction.

PMID- 28454815
TI  - Response to letter to the editor by Dr Tomoyuki Kawada.

PMID- 28454816
TI  - Letter to Editor.

PMID- 28454817
TI  - Reply to comment by Elbadawi et al.

PMID- 28454818
TI  - Plasma immune protein analysis in the orange-spotted grouper Epinephelus
      coioides: Evidence for altered expressions of immune factors associated with a
      choline-supplemented diet.
AB  - This study aimed to unravel the regulatory roles of choline in activating immune
      responses and disease resistance of the orange-spotted grouper Epinephelus
      coioides. Fish were fed a choline-supplemented diet at 1 g kg-1 of feed for 30
      days. Fish fed a fish meal basal diet without choline-supplement served as
      controls. At the end of the feeding trial, fish were challenged with Vibrio
      alginolyticus. Meanwhile, plasma proteomics of fish in each group were also
      evaluated by two-dimensional gel electrophoresis (2-DE), and differentially
      expressed proteins were identified by tandem mass spectrophotometry (MS/MS), then
      a Western blot analysis or real-time polymerase chain reaction was used to
      confirm differential expressions of immune-enhancing proteins. Results showed
      that choline significantly increased survival of E. coioides 48 days after being
      injected with V. alginolyticus. From maps of plasma proteins, a comparative
      analysis between the control and choline groups revealed that 111 spots matched,
      with 26 altered expression spots in the choline group. Of these 26 spots, 16 were
      upregulated and 10 downregulated. After protein identification by reverse-phase
      nano-high-performance liquid chromatography-electrospray ionization MS/MS
      analysis, eight of 26 proteins were found to be immune-related proteins, all of
      which were upregulated, including complement 3 (C3), alpha-2-macroglobulin-P-like
      isoform (A2M), fibrinogen beta chain precursor (FBG), and immunoglobulin heavy
      constant mu (Ighm) proteins. Expression of the A2M protein and A2M enzyme
      activity in plasma of fish fed choline significantly increased compared to the
      control group. Additionally, A2M messenger (m)RNA transcripts were also
      upregulated in the liver and kidneys. Significantly higher C3 expressions at both
      the mRNA and protein levels were detected in the liver of fish in the choline
      group. Moreover, FBG gene expressions in the liver and kidneys significantly
      increased, while Ighm increased in the kidneys and spleen of fish in the choline
      group. Our results suggest that dietary administration of choline can protect
      grouper against bacterial infections through activating the complement system,
      thereby inducing antiprotease activity and natural antibodies that play important
      roles in the innate immune system of fish.

PMID- 28454819
TI  - Causal role of the posterior parietal cortex for two-digit mental subtraction and
      addition: A repetitive TMS study.
AB  - Although parietal areas of the left hemisphere are known to be involved in simple
      mental calculation, the possible role of the homologue areas of the right
      hemisphere in mental complex calculation remains debated. In the present study,
      we tested the causal role of the posterior parietal cortex of both hemispheres in
      two-digit mental addition and subtraction by means of neuronavigated repetitive
      TMS (rTMS), investigating possible hemispheric asymmetries in specific parietal
      areas. In particular, we performed two rTMS experiments, which differed only for
      the target sites stimulated, on independent samples of participants. rTMS was
      delivered over the horizontal and ventral portions of the intraparietal sulcus
      (HIPS and VIPS, respectively) of each hemisphere in Experiment 1, and over the
      angular and supramarginal gyri (ANG and SMG, respectively) of each hemisphere in
      Experiment 2. First, we found that each cerebral area of the posterior parietal
      cortex is involved to some degree in the two-digit addition and subtraction.
      Second, in Experiment 1, we found a stronger pattern of hemispheric asymmetry for
      the involvement of HIPS in addition compared to subtraction. In particular,
      results showed a greater involvement of the right HIPS than the left one for
      addition. Moreover, we found less asymmetry for the VIPS. Taken together, these
      results suggest that two-digit mental addition is more strongly associated with
      the use of a spatial mapping compared to subtraction. In support of this view, in
      Experiment 2, a greater role of left and right ANG was found for addition needed
      in verbal processing of numbers and in visuospatial attention processes,
      respectively. We also revealed a greater involvement of the bilateral SMG in two
      digit mental subtraction, in response to greater working memory load required to
      solve this latter operation compared to addition.

PMID- 28454820
TI  - Dynamic spatiotemporal variability of alpha-BOLD relationships during the resting
      state and task-evoked responses.
AB  - Accurate characterization of the spatiotemporal relationship between two of the
      most prominent neuroimaging measures of neuronal activity, the 8-13Hz, occipito
      parietal EEG alpha oscillation and the BOLD fMRI signal, must encompass the
      intrinsically dynamic nature of both alpha power and brain function. Here, during
      the eyes-open resting state, we use a 16s sliding-window analysis and demonstrate
      that the mean spatial network of dynamic alpha-BOLD correlations is highly
      comparable to the static network calculated over six minutes. However, alpha-BOLD
      correlations showed substantial spatiotemporal variability within-subjects and
      passed through many different configurations such that the static network was
      fully represented in only ~10% of 16s epochs, with visual and parietal regions
      (coherent on average) often opposingly correlated with each other or with alpha.
      We find that the common assumption of static-alpha BOLD correlations greatly
      oversimplifies temporal variation in brain network dynamics. Fluctuations in
      alpha-BOLD coupling significantly depended upon the instantaneous amplitude of
      alpha power, and primary and lateral visual areas were most strongly negatively
      correlated with alpha during different alpha power states, possibly suggesting
      the action of multiple alpha mechanisms. Dynamic alpha-BOLD correlations could
      not be explained by eye-blinks/movements, head motion or non-neuronal
      physiological variability. Individual's mean alpha power and frequency were found
      to contribute to between-subject variability in alpha-BOLD correlations.
      Additionally, application to a visual stimulation dataset showed that dynamic
      alpha-BOLD correlations provided functional information pertaining to the brain's
      response to stimulation by exhibiting spatiotemporal fluctuations related to
      variability in the trial-by-trial BOLD response magnitude. Significantly weaker
      visual alpha-BOLD correlations were found both preceding and following small
      amplitude BOLD response trials compared to large response trials.

PMID- 28454821
TI  - Attentional processes, not implicit mentalizing, mediate performance in a
      perspective-taking task: Evidence from stimulation of the temporoparietal
      junction.
AB  - Mentalizing is a fundamental process underpinning human social interaction.
      Claims of the existence of 'implicit mentalizing' represent a fundamental shift
      in our understanding of this important skill, suggesting that preverbal infants
      and even animals may be capable of mentalizing. One of the most influential tasks
      supporting such claims in adults is the dot perspective-taking task, but
      demonstrations of similar performance on this task for mentalistic and non
      mentalistic stimuli have led to the suggestion that this task in fact measures
      domain-general processes, rather than implicit mentalizing. A mentalizing
      explanation was supported by fMRI data claiming to show greater activation of
      brain areas involved in mentalizing, including right temporoparietal junction
      (rTPJ), when participants made self-perspective judgements in a mentalistic, but
      not in a non-mentalistic condition, an interpretation subsequently challenged.
      Here we provide the first causal test of the mentalizing claim using disruptive
      transcranial magnetic stimulation of rTPJ during self-perspective judgements. We
      found no evidence for a distinction between mentalistic and non-mentalistic
      stimuli: stimulation of rTPJ impaired performance on all self-perspective trials,
      regardless of the mentalistic/non-mentalistic nature of the stimulus. Our data
      support a domain-general attentional interpretation of performance on the dot
      perspective-taking task, a role which is subserved by the rTPJ.

PMID- 28454822
TI  - Noncardiac chest pain after acute myocardial infarction: Frequency and
      association with health status outcomes.
AB  - BACKGROUND: The frequency of noncardiac chest pain (CP) hospitalization after
      acute myocardial infarction (AMI) is unknown, and its significance from patients'
      perspectives is not studied. OBJECTIVES: To assess the frequency of noncardiac CP
      admissions after AMI and its association with patients' self-reported health
      status. METHODS: We identified cardiac and noncardiac CP hospitalizations in the
      year after AMI from the 24-center TRIUMPH registry. Hierarchical repeated
      measures regression was used to identify the association of these
      hospitalizations with patients' self-reported health status using the Seattle
      Angina Questionnaire Quality of Life domain (SAQ QoL) and Short Form 12 (SF-12)
      physical (PCS) and mental (MCS) component summary scores. RESULTS: Of 3,099
      patients, 318 (10.3%) were hospitalized with CP, of whom 92 (28.9%) were
      hospitalized for noncardiac CP. Compared with patients not hospitalized with CP,
      noncardiac CP hospitalization was associated with poorer health status (SAQ QoL
      adjusted differences: -8.9 points [95% CI -12.1 to -5.6]; SF-12 PCS: -2.5 points
      [95% CI -4.2 to -0.8] and SF-12 MCS: -3.5 points [95% CI -5.1 to -1.9]). The SAQ
      QoL for patients hospitalized with noncardiac CP was similar to patients
      hospitalized with cardiac CP (adjusted difference: 0.6 points [95% CI -3.2 to
      4.5]; SF-12 PCS (0.9 points [95% CI -1.1 to 2.9]), but was worse with regard to
      SF-12 MCS (adjusted difference: -2.0 points [95% CI -3.9 to -0.2]). CONCLUSIONS:
      Noncardiac CP accounted for a third of CP hospitalizations within 1 year of AMI
      and was associated with similar disease-specific QoL as well as general physical
      and mental health status impairment compared with cardiac CP hospitalization.

PMID- 28454824
TI  - The impact of body mass index on the wearable cardioverter defibrillator shock
      efficacy and patient wear time.
AB  - BACKGROUND: The impact of body mass index (BMI) on the shock efficacy and patient
      adherence among patients using a wearable cardioverter defibrillator (WCD) is
      unknown. METHODS: Patients prescribed the WCD between January 1, 2008 and June 1,
      2013, who experienced at least one episode of sustained ventricular tachycardia
      (VT) or ventricular fibrillation (VF) and who received appropriate WCD therapy,
      were identified within a registry maintained by the manufacturer for regulatory,
      reimbursement, and administrative purposes. The registry contained patients' Body
      Mass Index (BMI) which was categorized as normal (18.0<BMI<25.0), overweight
      (25.0<=BMI<30.0) or obese (30.0>=BMI). Demographics, indication for WCD
      prescription and other clinical information were reviewed. Device-stored ECG,
      transthoracic impedance (TTI) and time worn were downloaded for analyses. A post
      shock rhythm which was no longer VT or VF was considered a successful
      tachyarrhythmia conversion. Only the first-shock arrhythmia conversion and TTI
      were included in the analyses. RESULTS: A total of 574 patients were included in
      the final analyses. Patient characteristics were similar across all groups except
      the obese group (60+/-11 years) was younger than the normal (63+/-16 years) and
      overweight (64+/-12 years, P=.001) groups. Mean length of use for normal,
      overweight and obese groups was 79+/-131, 82+/-202 and 55+/-97 days (P=.12),
      respectively; the median daily wear time was 21 hours among all groups. In a
      total of 623 VT/VF events, the median TTI was 44 ohms, 51 ohms and 65 ohms for
      normal, overweight and obese groups, respectively; TTI was positively correlated
      to BMI (r=0.33, P<.01). First-shock conversion rate was 92.9% in the normal
      group, 93.6% and 93.9% in the overweight and obese groups, respectively (P=.93).
      There was no difference in 24-hour survival among the three groups (91.9%, 94.1%
      and 92.3%, P=.66). CONCLUSION: The WCD first-shock success rate and post-event 24
      hour survival were high and independent from BMI. TTI was positively correlated
      with BMI but did not impact early clinical outcome. WCD was safe to all BMI
      groups and the patient wear time was excellent across all groups.

PMID- 28454823
TI  - Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The
      iNOPE trial.
AB  - BACKGROUND: The study hypothesis is that administration of inhaled nitric oxide
      (NO) plus oxygen to subjects with submassive pulmonary embolism (PE) will improve
      right ventricular (RV) systolic function and reduce RV strain and necrosis, while
      improving patient dyspnea, more than treatment with oxygen alone. METHODS: This
      article describes the rationale and protocol for a registered (NCT01939301),
      nearly completed phase II, 3-center, randomized, double-blind, controlled trial.
      Eligible patients have pulmonary imaging-proven acute PE. Subjects must be
      normotensive, and have RV dysfunction on echocardiography or elevated troponin or
      brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen
      or placebo for 24 hours (+/-3 hours) with blood sampling before and after
      treatment, and mandatory echocardiography and high-sensitivity troponin
      posttreatment to assess the composite primary end point. The sample size of N=78
      was predicated on 30% more NO-treated patients having a normal high-sensitivity
      troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with
      alpha=.05 and beta=.20. Safety was ensured by continuous spectrophotometric
      monitoring of percentage of methemoglobinemia and a predefined protocol to
      respond to emergent changes in condition. Blinding was ensured by identical
      tanks, software, and physical shielding of the device display and query of the
      clinical care team to assess blinding efficacy. RESULTS: We have enrolled 78
      patients over a 31-month period. No patient has been withdrawn as a result of a
      safety concern, and no patient has had a serious adverse event related to NO.
      CONCLUSIONS: We present methods and a protocol for the first double-blinded,
      randomized trial of inhaled NO to treat PE.

PMID- 28454825
TI  - Incomplete revascularization for percutaneous coronary interventions: Variation
      among operators, and association with operator and hospital characteristics.
AB  - BACKGROUND: Many studies have compared outcomes for incomplete revascularization
      (IR) among patients undergoing percutaneous coronary interventions (PCIs), but
      little is known about the correlates of IR, the extent to which complete
      revascularization (CR) was attempted unsuccessfully, and the variation across
      operators in the use of IR. METHODS: New York's PCI registry was used to examine
      medium-term mortality for IR, the variables associated with the use of IR, and
      the variation across operators in the utilization of IR after controlling for
      patient factors. RESULTS: Incomplete revascularization occurred for 63% of all
      patients and was significantly associated with higher 3-year mortality (adjusted
      hazard ratio1.35, 95% CI 1.23-1.48) than for CR. A total of 96% of all attempted
      CRs were successful. Operators with 15 or fewer years in practice (the lowest
      half) used IR significantly more (65% vs 61%, adjusted odds ratio [AOR] 1.17, 95%
      CI 1.00-1.37) than other operators, and operators with annual volumes of 171 or
      lower (the lowest 3 quartiles) used IR more than other operators (68% vs 60%, AOR
      1.35, 95% CI 1.14-1.59). Also, hospitals with annual volumes of 645 and lower
      (the lowest 50% of hospitals) used IR more (67% vs 62%, AOR 1.46, 95% CI 1.07
      1.99) than other hospitals. CONCLUSIONS: Percutaneous coronary intervention
      patients without myocardial infarction who undergo IR continue to have higher
      medium-term (3-year) risk-adjusted mortality rates. There is a large amount of
      variability among operators in the frequency with which IR occurs. Operators who
      have been in practice longer, and higher-volume operators and hospitals have
      lower rates of IR. Failed attempts at CR occur very infrequently.

PMID- 28454826
TI  - Outcomes in adult Fontan patients with atrial tachyarrhythmias.
AB  - BACKGROUND: The optimal management strategy for atrial tachyarrhythmia in the
      Fontan population is unknown. METHODS: Retrospective review of 264 adult Fontan
      patients with atrial tachyarrhythmia evaluating 3 clinically adopted scenarios:
      antiarrhythmic drug (AAD) therapy, catheter ablation (CA), and Fontan conversion
      (FC). These patients were followed up at Mayo Clinic from 1994 to 2014. The study
      objective was to compare freedom from atrial tachyarrhythmia recurrence (AR) and
      occurrence of composite adverse events (stroke, heart failure hospitalization,
      death, or heart transplant) between treatment groups. RESULTS: The age of atrial
      tachyarrhythmia onset was 25 +/- 4 years, time from Fontan operation was 13 +/- 6
      years, follow-up was 74 +/- 18 months, atriopulmonary Fontan was 215 (81%), and
      atrial flutter/intra-atrial reentry tachycardia was 173 (65%). In those managed
      with AAD (n = 110), freedom from AR was 7% at 60 months. Catheter ablation (n =
      31) was associated with an acute procedural success of 94%, and freedom from AR
      was 41% at 60 months. Fontan conversion (n = 33) resulted in a perioperative
      mortality of 3%, and freedom from AR was 51% at 60 months. Fontan conversion and
      CA were similar with regard to AR (P = .14) and significantly better compared
      with AAD (P < .0001). Adverse events were found to occur more frequently in the
      patients with AR (P < .0001) and the patients treated with AAD only (P < .0001).
      CONCLUSIONS: Catheter ablation and FC operations are associated with less
      recurrence of atrial tachyarrhythmia compared with AAD. Atrial tachyarrhythmias
      are more likely to recur in patients with a longer history of the arrhythmia and
      are associated with more adverse events. Early referral to a specialty center for
      these interventions should be considered.

PMID- 28454827
TI  - Cardiac rehabilitation in heart failure with reduced ejection fraction: A "take
      it or leave it" intervention.

PMID- 28454828
TI  - Aerobic exercise training and general health status in ambulatory heart failure
      patients with a reduced ejection fraction-Findings from the Heart Failure and A
      Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)trial.
AB  - BACKGROUND: Although aerobic exercise improves quality of life as assessed by a
      disease-specific instrument in ambulatory HF patients with a reduced ejection
      fraction (EF), the impact of an exercise intervention on general health status
      has not been previously reported. METHODS: A secondary analysis was performed of
      the HF-ACTION trial (ClinicalTrials.gov Number: NCT00047437), which enrolled 2331
      medically stable outpatients with HF and an EF <=35% and randomized them to
      aerobic exercise training, consisting of 36 supervised sessions followed by home
      based training versus usual care for a median follow-up of 30 months. The EuroQOL
      5-dimension questionnaire (EQ-5D) was administered to study participants at
      baseline, 3 months, and 12 months. EQ-5D includes functional dimensions (ie,
      mobility, self-care, usual activities, pain/discomfort, and anxiety/depression),
      which were mapped to corresponding utility scores (ie, 0=death and 1=perfect
      health), and a visual analogue scale (VAS) ranging from 0 (ie, "worst imaginable
      health state") to 100 (ie, "best imaginable health state"). RESULTS: Study
      participants had a median (25th, 75th) age of 59 (51, 68) years and 71% were
      male. A history of ischemic heart disease was reported in 51% of participants and
      the EF was 25% (20%, 30%). Baseline VAS and mapped utility scores were 65+/-19
      and 0.81+/-0.14. Exercise training led to an improvement in VAS score compared
      with usual care from baseline to 3 months (exercise training: 6+/-17 vs usual
      care: 3+/-20; P <.01) although there were no further significant changes at 12
      months. Aerobic exercise training did not favorably change mapped utility scores
      over either timeframe. After multivariable adjustment, lower mapped utility
      (hazard ratio [HR] 1.19 per 0.1 decrease, 95% CI 1.09-1.29; P < .0001) and VAS
      scores (HR 1.05 per 10 point decrease, 95% CI 1.02-1.08; P < .01) at baseline
      were associated with increased risk of death or hospitalization. CONCLUSION:
      Ambulatory HF patients with a reduced EF had impaired health status at baseline
      which was associated with increased morbidity and mortality, in part mitigated by
      a structured aerobic exercise regimen.

PMID- 28454829
TI  - Design and rationale of the COMPARE-ACUTE trial: Fractional flow reserve-guided
      primary multivessel percutaneous coronary intervention to improve guideline
      indexed actual standard of care for treatment of ST-elevation myocardial
      infarction in patients with multivessel coronary disease.
AB  - : What the best strategy is for nonculprit lesions in ST-elevation myocardial
      infarction (STEMI) patients presenting with multivessel disease remains a
      clinical dilemma. Based on recent clinical studies suggesting that complete
      revascularization in the acute phase is beneficial, the European Society of
      Cardiology and American College of Cardiology/American Heart Association
      guidelines have been recently changed from class 3 discouragement to a class 2B
      recommendation concerning the treatment of the nonculprit lesions in the acute
      index procedure. However, in these recent studies, nonculprit lesion treatment
      was guided by angiography, which is known for its poor accuracy in determining
      ischemia. Fractional flow reserve (FFR) guidance for treatment of nonculprit
      vessels seems to be a reasonable approach, and in the acute setting of STEMI, it
      is not yet investigated. The COMPARE-ACUTE trial aims to investigate FFR-guided
      complete revascularization in comparison to a culprit lesion treatment-only
      strategy in STEMI patients with multivessel disease presenting for primary
      percutaneous coronary intervention. METHODS AND RESULTS: COMPARE-ACUTE is an
      investigator-initiated, prospective multicenter randomized controlled trial.
      After successful primary percutaneous coronary intervention, patients will be
      randomized in a 1:2 fashion toward FFR-guided complete revascularization or
      culprit lesion treatment-only strategies. The chosen primary end point is a
      composite of all-cause mortality, nonfatal myocardial infarction, any
      revascularization, and cerebrovascular events (major adverse cardiac and
      cerebrovascular events) at 12 months, with 3-year follow-up. Based on estimated
      event rates, a sample size of 885 patients is needed to show superiority of the
      FFR-guided revascularization with 80% power. CONCLUSION: The aim of the COMPARE
      ACUTE trial is to assess whether FFR-guided complete revascularization in the
      acute setting is superior to culprit lesion treatment-only therapy.

PMID- 28454830
TI  - National patterns in intensity and frequency of outpatient care for apparent
      treatment-resistant hypertension.
AB  - BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is associated with
      an increased risk of adverse cardiovascular outcomes. We studied the frequency
      and intensity of care for aTRH among participants aged 65 years and older in the
      US-based REGARDS study linked with Medicare claims. METHODS: Blood pressure (BP)
      was measured twice and averaged. aTRH was defined by the use of >=3 classes of
      antihypertensive medication and uncontrolled BP (UaTRH, systolic/diastolic BP
      >=140/90 mmHg), or >=4 classes with controlled BP (CaTRH). Participants were
      categorized as not having aTRH (no aTRH), CaTRH or UaTRH. RESULTS: Among 4650
      participants with hypertension, 468 (10.1%) had UaTRH, 247 (5.3%) had CaTRH, and
      3935 (84.6%) had hypertension but did not have aTRH. For hypertension-related
      visits, those with UaTRH saw primary care physicians and cardiologists more
      frequently than those without aTRH (mean primary care visits per year: 2.77 vs
      2.27, P<.001; cardiologists: 0.50 vs 0.35, P=.014). Among those with UaTRH,
      CaTRH, and no aTRH, respectively 73.5%, 68.0%, and 67.5% had >1 hypertension
      related visit per year. Among those with UaTRH, males vs females (prevalence
      ratio=0.78; 95% CI 0.69-0.89), whites vs blacks (0.88; 95% CI 0.78-0.99), and
      current smokers vs non-smokers (0.66; 95% CI 0.48-0.89) were less likely to
      receive >1 hypertension-related visit per year. Diagnostic intensity, measured by
      testing for end organ damage and secondary hypertension, was similar between
      groups. CONCLUSIONS: Many people with UaTRH are not seen more than once per year
      for hypertension and may benefit from increased care.

PMID- 28454831
TI  - Rationale and design of the Medication adherence Improvement Support App For
      Engagement-Blood Pressure (MedISAFE-BP) trial.
AB  - BACKGROUND: Hypertension is a major contributor to the health and economic burden
      imposed by stroke, heart disease, and renal insufficiency. Antihypertensives can
      prevent many of the harmful effects of elevated blood pressure, but medication
      nonadherence is a known barrier to the effectiveness of these treatments.
      Smartphone-based applications that remind patients to take their medications,
      provide education, and allow for social interactions between individuals with
      similar health concerns have been widely advocated as a strategy to improve
      adherence but have not been subject to rigorous testing. METHODS/DESIGN: The
      MedISAFE-BP study is a prospective, randomized control trial designed to evaluate
      the impact on blood pressure and medication adherence of an mhealth application
      (Medisafe). Four hundred thirteen patients with uncontrolled hypertension have
      been enrolled and randomized in a 1:1 fashion to usual care or to the use of the
      Medisafe mhealth platform. Patients will be followed up for 12 weeks and the
      trial's co-primary outcomes will be change in systolic blood pressure and self
      reported medication adherence. DISCUSSION: The MedISAFE-BP trial is the first
      study to rigorously evaluate an mhealth application's effect on blood pressure
      and medication adherence. The results will inform the potential effectiveness of
      this simple system in improving cardiovascular disease risk factors and clinical
      outcomes.

PMID- 28454832
TI  - Rationale and design of the Coronary Computed Tomographic Angiography for
      Selective Cardiac Catheterization: Relation to Cardiovascular Outcomes, Cost
      Effectiveness and Quality of Life (CONSERVE) trial.
AB  - : Although coronary computed tomography angiography (CCTA) has shown promise as a
      "gatekeeper" to invasive coronary angiography (ICA) in longitudinal cohort
      studies, it remains unknown whether the strategy of selective ICA by initial
      performance of CCTA is either safe or effective when compared with a direct ICA
      strategy in patients with an American Heart Association (AHA)/American College of
      Cardiology (ACC) guideline-directed indication for ICA. OBJECTIVES: The CONSERVE
      trial is a prospective randomized multicenter trial to determine the clinical
      effectiveness of "selective catheterization" vs "direct catheterization"
      strategies for stable patients with suspected but without known coronary artery
      disease, who meet AHA/ACC guideline indication for ICA. METHODS: Patients being
      referred for clinically indicated nonemergent ICA with an AHA/ACC class II
      guideline indication for ICA will be randomized to either direct catheterization
      or selective catheterization strategy. Patients in the direct catheterization arm
      will proceed directly to ICA as planned, whereas patients in the select
      catheterization arm will undergo initial CCTA, followed by ICA at the discretion
      of the site physician. All CCTAs and ICAs will be interpreted on site. Follow-up
      testing and/or therapy after CCTA or ICA will be at the discretion of the site
      physician. RESULTS: This trial will report a primary clinical end point of
      noninferiority rates of major adverse cardiac events, as defined by the composite
      of death, nonfatal myocardial infarction, unstable angina, stroke, urgent or
      emergent coronary revascularization, or cardiac hospitalization. CONCLUSION: The
      CONSERVE trial will determine whether selective catheterization strategy, based
      on initial CCTA in patients being referred to ICA, is safe and effective.

PMID- 28454833
TI  - Changes in cardiovascular medication after coronary artery calcium scanning and
      normal single photon emission computed tomography myocardial perfusion imaging in
      symptomatic patients.
AB  - : The impact of coronary artery calcium (CAC) scoring on subsequent changes in
      cardiovascular medication use in symptomatic patients with normal myocardial
      perfusion imaging (MPI) findings is not well established. The aim of the current
      study was to evaluate changes in aspirin and statin use in patients suspected for
      coronary artery disease after CAC scoring and normal single photon emission
      computed tomography (SPECT) MPI. METHODS: In the current study, 1,033 stable
      symptomatic patients without a known history of coronary artery disease with
      normal SPECT MPI who underwent concomitant CAC scoring were included. All
      patients had a clinical indication for imaging, mainly atypical chest pain and
      dyspnea, and were referred from the outpatient clinic of our hospital. Data
      regarding posttest medication change (either starting or discontinuation of
      aspirin and statin therapy at the subsequent outpatient visit) were
      retrospectively collected. Patients were categorized into 4 groups based on their
      CAC score. RESULTS: Mean age of the patients was 61+/-11 years and 39% were male.
      At baseline, 35% of the patients used aspirin and 39% used statin. In patients
      with CAC scores 0, 1-99, 100-399, and >=400, aspirin was started in 1%, 4%, 9%,
      and 9%, respectively, and statin was started in 0%, 7%, 18%, and 24% of the
      patients, respectively (P<.001). Aspirin was discontinued in 19%, 11%, 7%, and 1%
      and statin was discontinued in 8%, 6%, 2%, and 0% (P<.001) of the patients in
      these respective CAC score categories. After correction for differences in risk
      factors and baseline medication use, increased CAC was independently associated
      with posttest aspirin (odds ratio 4.6, 11.2, and 27.1 for CAC scores 1-99, 100
      399, and >=400, respectively; P<.001) and statin use (odds ratio 4.4, 19.4, and
      60.9 for CAC scores 1-99, 100-399, and >=400, respectively; P<.001). CONCLUSIONS:
      Higher CAC scores are associated with the initiation of aspirin and statin
      therapy in patients with normal SPECT MPI. In patients with lower CAC scores,
      discontinuation of cardioprotective medication is more likely. CAC score is
      independently associated with posttest statin and aspirin use.

PMID- 28454834
TI  - Trends in health care expenditure among US adults with heart failure: The Medical
      Expenditure Panel Survey 2002-2011.
AB  - : Population-based national data on the trends in expenditures related to heart
      failure (HF) are scarce. Assessing the time trends in health care expenditures
      for HF in the United States can help to better define the burden of this
      condition. METHODS: Using 10-year data (2002-2011) from the national Medical
      Expenditure Panel Survey (weighted sample of 188,708,194US adults aged >=18years)
      and a 2-part model (adjusting for demographics, comorbidities, and time); we
      estimated adjusted mean and incremental medical expenditures by HF status. The
      costs were direct total health care expenditures (out-of-pocket payments and
      payments by private insurance, Medicaid, Medicare, and other sources) from
      various sources (office-based visits, hospital outpatient, emergency department,
      inpatient hospital, pharmacy, home health care, and other medical expenditures).
      RESULTS: Compared with expenditures for individuals without HF ($5511 [95% CI
      5405-5617]), individuals with HF had a 4-fold higher mean expenditures of
      ($23,854 [95% CI 21,733-25,975]). Individuals with HF had $3446 (95% CI 2592
      4299) higher direct incremental expenditures compared with those without HF,
      after adjusting for demographics and comorbidities. Among those with HF, costs
      continuously increased by $5836 (28% relative increase), from $21,316 (95% CI
      18,359-24,272) in 2002/2003 to $27,152 (95% CI 20,066-34,237) in 2010/2011, and
      inpatient costs ($11,318 over the whole period) were the single largest component
      of total medical expenditure. The estimated unadjusted total direct medical
      expenditures for US adults with HF were $30 billion/y and the adjusted total
      incremental expenditure was $5.8 billion/y. CONCLUSIONS: Heart failure is costly
      and over a recent 10-year period, and direct expenditure related to HF increased
      markedly, mainly driven by inpatient costs.

PMID- 28454835
TI  - Noncardiovascular deaths are more common than cardiovascular deaths in patients
      with cardiovascular disease or cardiovascular risk factors and impaired glucose
      tolerance: Insights from the Nateglinide and Valsartan in Impaired Glucose
      Tolerance Outcomes Research (NAVIGATOR) trial.
AB  - BACKGROUND: Patients with impaired glucose tolerance have an elevated risk of
      cardiovascular (CV) death; however, the causes and risk factors associated with
      non-CV deaths are poorly understood. METHODS: The NAVIGATOR trial enrolled 9,306
      participants with impaired glucose tolerance and CV disease or at high CV risk,
      with a median follow-up of 6.4years. Using this population, we identified (1) the
      proportion of deaths attributed to CV, non-CV, and unknown causes, and (2) the
      risk factors associated with non-CV death. RESULTS: During the NAVIGATOR trial
      follow-up, 622 patients died. Investigators reported 244 (39.2%) CV deaths, 313
      (50.3%) non-CV deaths, and 65 (10.5%) deaths of unknown cause. Myocardial
      infarction was the leading cause of investigator-reported death (57/622 [9.2%]).
      Among non-CV deaths, the most commonly identified cause related to malignancy
      (177/313 [56.5%]). Using adjudicated causes of death, Cox proportional hazard
      models identified 3 independent prognostic markers that increased the risk of non
      CV death: history of non-melanoma skin cancer (hazard ratio 2.67 [95% CI 1.65
      4.33]; P<.0001), white blood cell count (1 unit >5000/mm3; 1.10 [1.02-1.18];
      P=.011), and serum potassium levels (per 1mmol/L above any value; 1.67
      [1.302.15]; P<.0001). CONCLUSIONS: Despite the high baseline CV risk among
      patients in the NAVIGATOR trial, the most common cause of death was non-CV. The
      high burden of non-CV death in this population has potential implications for
      future CV event-driven trials.

PMID- 28454836
TI  - Right vEntricular Dysfunction in tEtralogy of Fallot: INhibition of the rEnin
      angiotensin-aldosterone system (REDEFINE) trial: Rationale and design of a
      randomized, double-blind, placebo-controlled clinical trial.
AB  - : Renin-angiotensin-aldosterone system (RAAS) inhibition with angiotensin II
      receptor blockers or angiotensin-converting enzyme inhibitors is beneficial in
      patients with acquired left ventricular dysfunction. Adult patients with
      tetralogy of Fallot (TOF) with right ventricular (RV) dysfunction are at high
      risk for heart failure, arrhythmias, and sudden cardiac death. However, the
      efficacy of RAAS inhibition has not been established in these patients. METHODS:
      The REDEFINE is an investigator-initiated, multicenter, prospective, randomized,
      double-blind, placebo-controlled trial to study the effects of the angiotensin II
      receptor blocker losartan (target dosage of 150 mg once daily) in adult patients
      with TOF. Patients with RV dysfunction in the absence of severe valvular
      dysfunction are eligible for inclusion. The primary end point is the change in RV
      ejection fraction after 18 to 24 months, as measured by cardiovascular magnetic
      resonance imaging. In addition, laboratory measurements, echocardiography, and
      cardiopulmonary exercise testing are performed. CONCLUSION: The REDEFINE trial
      will study the effects of RAAS inhibition with losartan in TOF patients with RV
      dysfunction.

PMID- 28454837
TI  - Balancing the risk of spontaneous ischemic and major bleeding events in acute
      coronary syndromes.
AB  - : Evaluation of antithrombotic treatments for acute coronary syndromes (ACS)
      requires balancing ischemic and bleeding risks to assess net benefit. We sought
      to compare the relative effects of ischemic and bleeding events on mortality.
      METHODS: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we
      compared spontaneous ischemic events (myocardial infarction or stroke) with
      spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial
      Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect
      to risk of mortality using time-dependent Cox proportional hazards models. The
      comparison was performed using ratio of hazard ratios for mortality increase
      after ischemic vs bleeding events. RESULTS: A total of 822 patients (4.4%) had
      >=1 spontaneous ischemic event; 485 patients (2.6%), >=1 spontaneous PLATO major
      bleed, 282 (1.5%), >=1 spontaneous TIMI major bleed; and 207 (1.1%), >=1
      spontaneous severe GUSTO bleed. In patients who had both events, bleeding
      occurred first in most patients. Regardless of classification, major bleeding
      events were associated with increased short- and long-term mortality that were
      not significantly different from the increase associated with spontaneous
      ischemic events: ratio of hazard ratios (95% CIs) for short- and long-term
      mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and
      0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI
      major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P>0.05)
      CONCLUSIONS: In patients with ACS on dual antiplatelet therapy, spontaneous major
      bleeding events seem "prognostically equivalent" to spontaneous ischemic
      complications. This result allows quantitative comparisons between both actual
      and predicted bleeding and ischemic risks. Our findings help to better define net
      clinical benefit of antithrombotic treatments and more accurately estimate
      mortality after ischemic and bleeding events in patients with ACS.

PMID- 28454838
TI  - Bendopnea: The next prognostic marker of advanced heart failure?

PMID- 28454839
TI  - Response to letter by Dziewierz et al on "Influence of access site choice for
      cardiac catheterization on risk of adverse neurological events: A systematic
      review and meta-analysis". Am Heart J 2016;181:107-119.

PMID- 28454840
TI  - Transradial access and the risk of periprocedural stroke.

PMID- 28454841
TI  - Assisted and Unassisted Protein Insertion into Liposomes.
AB  - The insertion of newly synthesized membrane proteins is a well-regulated and
      fascinating process occurring in every living cell. Several translocases and
      insertases have been found in prokaryotic and eukaryotic cells, the Sec61 complex
      and the Get complex in the endoplasmic reticulum and the SecYEG complex and YidC
      in bacteria and archaea. In mitochondria, TOM and TIM complexes transport nuclear
      encoded proteins, whereas the Oxa1 is required for the insertion of mitochondria
      encoded membrane proteins. Related to the bacterial YidC and the mitochondrial
      Oxa1 are the Alb3 and Alb4 proteins in chloroplasts. These membrane insertases
      are comparably simple and can be studied in vitro, after their biochemical
      purification and reconstitution in artificial lipid bilayers such as liposomes or
      nanodiscs. Here, we describe the recent progress to study the molecular mechanism
      of YidC-dependent and unassisted membrane insertion at the single molecule level.

PMID- 28454842
TI  - Inactivation of Planktonic Escherichia coli by Focused 2-MHz Ultrasound.
AB  - This study was motivated by the desire to develop a non-invasive means to treat
      abscesses, and represents the first steps toward that goal. Non-thermal, high
      intensity focused ultrasound (HIFU) was used to inactivate Escherichia coli (~1 *
      109 cells/mL) in suspension. Cells were treated in 96-well culture plate wells
      using 1.95-MHz ultrasound and incident focal acoustic pressures as high as 16 MPa
      peak positive and 9.9 MPa peak negative (free field measurements). The surviving
      fraction was assessed by coliform culture and the alamarBlue assay. No
      biologically significant heating was associated with ultrasound exposure.
      Bacterial inactivation kinetics were well described by a half-life model, with a
      half-time of 1.2 min. At the highest exposure levels, a 2log inactivation was
      typically achieved within 10 min. The free field-equivalent peak negative
      acoustic pressure threshold for inactivation was ~7 MPa. At the highest acoustic
      pressures used, inactivation efficacy was insensitive to reciprocal changes in
      pulse length and pulse repetition frequency at constant duty factor. Although
      treated volumes were very small, proof of principle was provided by these
      experiments.

PMID- 28454844
TI  - Serum miRNAs miR-206, 143-3p and 374b-5p as potential biomarkers for amyotrophic
      lateral sclerosis (ALS).
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative condition
      characterized by loss of motor neurones and progressive muscle wasting. There is
      no diagnostic test for ALS therefore robust biomarkers would not only be valuable
      for diagnosis, but also for the classification of disease subtypes, monitoring
      responses to drugs and tracking disease progression. As regulators of gene
      expression, microRNAs (miRNAs) are increasingly used for diagnostic and
      prognostic purposes in various disease states with increasing exploration in
      neurodegenerative disorders. We hypothesize that circulating blood-based miRNAs
      will serve as biomarkers and use miRNA profiling to determine miRNA signatures
      from the serum of sporadic ALS patients compared to healthy controls and patients
      with diseases that mimic ALS. A number of differentially expressed miRNAs were
      identified in each set of patient comparisons. Validation in an additional
      patient cohort showed that miR-206 and miR-143-3p were increased and miR-374b-5p
      was decreased compared to controls. A continued change in miRNA expression
      persisted during disease progression indicating the potential use of these
      particular miRNAs as longitudinal biomarkers in ALS.

PMID- 28454843
TI  - Monitoring Microwave Ablation of Ex Vivo Bovine Liver Using Ultrasonic
      Attenuation Imaging.
AB  - Thermal ablation of soft tissue changes the tissue microstructure and,
      consequently, induces changes in its acoustic properties. Although B-mode
      ultrasound provides high-resolution and high-frame-rate images of ablative
      therapeutic procedures, it is not particularly effective at delineating
      boundaries of ablated regions because of poor contrast in echogenicity between
      ablated and surrounding normal tissue. Quantitative ultrasound techniques can
      provide quantitative estimates of acoustic properties, such as backscatter and
      attenuation coefficients, and differentiate ablated and unablated regions more
      effectively, with the potential for monitoring minimally invasive thermal
      therapies. In this study, a previously introduced attenuation estimation method
      was used to create quantitative attenuation coefficient maps for 11 microwave
      ablation procedures performed on refrigerated ex vivo bovine liver. The
      attenuation images correlate well with the pathologic images of the ablated
      region. The mean attenuation coefficient for regions of interest drawn inside and
      outside the ablated zones were 0.9 (+/-0.2) and 0.45 (+/-0.15) dB/cm/MHz,
      respectively. These estimates agree with reported values in the literature and
      establish the usefulness of non-invasive attenuation imaging for monitoring
      therapeutic procedures in the liver.

PMID- 28454846
TI  - AIDS-Related Mycoses: Current Progress in the Field and Future Priorities.
AB  - Opportunistic fungal infections continue to take an unacceptably heavy toll on
      the most disadvantaged living with HIV-AIDS, and are a major driver for HIV
      related deaths. At the second EMBO Workshop on AIDS-Related Mycoses, clinicians
      and scientists from around the world reported current progress and key priorities
      for improving outcomes from HIV-related mycoses.

PMID- 28454845
TI  - Abnormalities of cortical neural synchronization mechanisms in patients with
      dementia due to Alzheimer's and Lewy body diseases: an EEG study.
AB  - The aim of this retrospective exploratory study was that resting state eyes
      closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in
      patients with dementia due to Alzheimer's disease dementia (ADD), Parkinson's
      disease dementia (PDD), and dementia with Lewy body (DLB). Clinical and rsEEG
      data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were
      available in an international archive. Demography, education, and Mini-Mental
      State Evaluation score were not different between the patient groups. Individual
      alpha frequency peak (IAF) determined the delta, theta, alpha 1, alpha 2, and
      alpha 3 frequency bands. Fixed beta 1, beta 2, and gamma bands were also
      considered. rsEEG cortical sources were estimated by means of the exact low
      resolution brain electromagnetic source tomography and were then classified
      across individuals, on the basis of the receiver operating characteristic curves.
      Compared to Nold, IAF showed marked slowing in PDD and DLB and moderate slowing
      in ADD. Furthermore, all patient groups showed lower posterior alpha 2 source
      activities. This effect was dramatic in ADD, marked in DLB, and moderate in PDD.
      These groups also showed higher occipital delta source activities, but this
      effect was dramatic in PDD, marked in DLB, and moderate in ADD. The posterior
      delta and alpha sources allowed good classification accuracy (approximately 0.85
      0.90) between the Nold subjects and patients, and between ADD and PDD patients.
      In quiet wakefulness, delta and alpha sources unveiled different spatial and
      frequency features of the cortical neural synchronization underpinning brain
      arousal in ADD, PDD, and DLB patients. Future prospective cross-validation
      studies should test these rsEEG markers for clinical applications and drug
      discovery.

PMID- 28454847
TI  - Inherited mutations in DNA repair genes and cancer risk.
AB  - Although most cancer cases are due to somatic mutations, up to 10% of cases are
      attributable to germline mutations. This inherited cancer predisposition is
      mostly due to the loss of function of suppressor genes rather than the activation
      of oncogenes. Defects in DNA repair genes are the genetic events most commonly
      involved in hereditary cancers. The implementation of high-throughput sequencing
      in diagnostic testing has uncovered new predisposition genes. Furthermore, for
      some tumor types these sequencing techniques have also unveiled a prevalence of
      germline mutations significantly higher than previous estimations. The clinical
      implications of many of these repair defects are yet to be defined. Further
      studies will need to be conducted to establish the most appropriated management
      of unaffected carriers that are likely to grow in numbers. On the contrary, the
      presence of DNA repair defects provides a unique opportunity for the development
      of treatments that take advantage of a tumor feature. In this review article, we
      summarize not only the most common syndromes linked to DNA repair defects but
      also less known entities. We address the underlying genetics and the clinical
      implications of each DNA repair defect as well as the current recommendations for
      cancer surveillance.

PMID- 28454848
TI  - Design, synthesis, and evaluation of multitarget-directed ligands against
      Alzheimer's disease based on the fusion of donepezil and curcumin.
AB  - By fusing donepezil and curcumin, a novel series of compounds were obtained as
      multitarget-directed ligands against Alzheimer's disease. Among them, compound
      11b displayed potent acetylcholinesterase (AChE) inhibition (IC50=187nM) and the
      highest BuChE/AChE selectivity (66.3). Compound 11b also inhibited 45.3% Abeta1
      42 self-aggregation at 20MUM and displayed remarkable antioxidant effects. The
      metal-chelating property of compound 11b was elucidated by determining the 1:1
      stoichiometry for the 11b-Cu(II) complex. The excellent blood-brain barrier
      permeability of 11b also indicated the potential for the compound to penetrate
      the central nervous system.

PMID- 28454849
TI  - Synthesis and biological evaluation of novel selective androgen receptor
      modulators (SARMs) Part III: Discovery of 4-(5-oxopyrrolidine-1-yl)benzonitrile
      derivative 2f as a clinical candidate.
AB  - We previously reported that 4-(pyrrolidin-1-yl)benzonitrile derivative 1b was a
      selective androgen receptor modulator (SARM) that exhibited anabolic effects on
      organs such as muscles and the central nervous system (CNS), but neutral effects
      on the prostate. From further modification, we identified that 4-(5
      oxopyrrolidine-1-yl)benzonitrile derivative 2a showed strong AR binding affinity
      with improved metabolic stabilities. Based on these results, we tried to enhance
      the AR agonistic activities by modifying the substituents of the 5-oxopyrrolidine
      ring. As a consequence, we found that 4-[(2S,3S)-2-ethyl-3-hydroxy-5
      oxopyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile (2f) had ideal SARM profiles
      in Hershberger assay and sexual behavior induction assay. Furthermore, 2f showed
      good pharmacokinetic profiles in rats, dogs, monkeys, excellent nuclear
      selectivity and acceptable toxicological profiles. We also determined its binding
      mode by obtaining the co-crystal structures with AR.

PMID- 28454850
TI  - Procalcitonin for the early diagnosis of sepsis in burn patients: A retrospective
      study.
AB  - BACKGROUND: The gold standard for sepsis diagnosis in burn patient still relies
      on microbiological cultures, which take 48-72h to provide results, delaying the
      start of antimicrobial therapy. Thus, biomarkers allowing an earlier sepsis
      diagnosis in burn patients are needed. METHODS: This retrospective observational
      study included 150 burn patients with total burned surface area >=15%. Clinical
      diagnosis of sepsis among these patients was done according to the American Burn
      Association criteria. Biomarker (procalcitonin, white blood cells and platelet
      countings, prothrombinemia, D-dimers, C-reactive protein, blood lactate and
      temperature) values were available for 48 patients without sepsis (2767
      timepoints) and 102 patients with sepsis (652 timepoints). Quantitative variables
      were compared with Mann-Whitney tests and qualitative variables were compared
      with Pearson chi-square test. Effect size was measured by the probability of
      superiority. Receiver operating characteristic (ROC) curves evaluate capacity for
      sepsis diagnosis. Sensitivity, specificity, positive and negative predictive
      values were calculated for some cut-off values, including the best cut-off
      defined by the maximum of Youden index. RESULTS: Statistically significant
      differences between the groups of septic and non-septic patients, with medium to
      large effect size, were detected for all the biomarkers considered, except
      temperature. PCT was the biomarker with the largest AUC and effect size
      (AUC=0.71). Analysis of the PCT ROC curve showed that 0.5ng/mL cut-off presented
      highest sensitivity and lowest specificity, whereas 1.5ng/mL cut-off was
      associated with lowest sensitivity and highest specificity. CONCLUSION:
      Procalcitonin showed to be the best of the biomarkers studied for an early
      diagnosis of sepsis. Its use should be considered in antimicrobial stewardship
      programs in Burn Units.

PMID- 28454851
TI  - RE: "Ultrasound is a reproducible and valid tool for measuring scar height in
      children with burn scars: A cross-sectional study of the psychometric properties
      and utility of the ultrasound and 3D camera" by M. Simons, E. Gee Kee, R. Kimble,
      Z. Tyack [Burns 43 (2017) 993-1001].

PMID- 28454852
TI  - Epstein-Barr virus-positive mucocutaneous ulcer in Crohn's disease. A condition
      to consider in immunosuppressed IBD patients.
AB  - Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a little known entity
      that can affect the oropharyngeal mucosa, the gastrointestinal tract and the
      skin. The main risk factor for the development of this lesion is
      immunosuppression. Because its features are similar to other Epstein-Barr virus
      associated lymphoproliferative disorders, a differential diagnosis can sometimes
      prove challenging. Here, we report the case of a man diagnosed with Crohn's
      disease and treated with azathioprine and infliximab who developed ulceration at
      the rectum that was refractory to conventional medical treatment. Although the
      histological characteristics were suggestive of an EBVMCU, lymphoproliferative
      disease could not be ruled out. The patient did not improve after discontinuation
      of the treatment, a proctectomy was performed and the diagnosis of this disease
      was confirmed. Although very few cases of EBVMCU affecting the colon have been
      reported, its diagnosis should be always considered in refractory cases of
      inflammatory bowel disease with patients undergoing immunosuppressive treatment.

PMID- 28454853
TI  - Value of cross-sectional imaging in assessing active Crohn's disease before stoma
      reversal.
AB  - BACKGROUND: There are currently no guidelines on the need to assess disease
      activity before stoma reversal in Crohn's disease (CD). We sought to determine
      the value of cross-sectional imaging for detecting active CD before stoma
      reversal. METHODS: 38 CD patients underwent cross-sectional imaging before stoma
      reversal. CD activity was blindly evaluated by an independent radiologist.
      Postoperative outcomes were recorded. RESULTS: Before stoma reversal, cross
      sectional imaging identified active CD in 20 of the 38 study participants
      (52.6%). In 9 out of 10 tested patients, radiologic and endoscopic assessments
      gave concordant findings with regard to CD recurrence before stoma reversal.
      Stoma reversal was delayed in half of the patients with active CD and in none of
      the patients without active CD. Before stoma reversal, tumor necrosis factor
      alpha antagonists or immunosuppressants were initiated in 45% of the patients
      with active CD and 5.6% of the patients without active CD. In the year following
      stoma reversal, the recurrence rate (in a radiologic assessment) was higher in
      patients with active CD than in patients without active CD (75.0% vs. 30.8%,
      respectively; p=0.04). CONCLUSION: Cross-sectional imaging revealed postoperative
      recurrence in about a quarter of patients before stoma reversal; this finding may
      influence the postoperative treatment strategy and outcomes.

PMID- 28454854
TI  - Technological advances for improving adenoma detection rates: The changing face
      of colonoscopy.
AB  - Worldwide, colorectal cancer is the third commonest cancer. Over 90% follow an
      adenoma-to-cancer sequence over many years. Colonoscopy is the gold standard
      method for cancer screening and early adenoma detection. However, considerable
      variation exists between endoscopists' detection rates. This review considers the
      effects of different endoscopic techniques on adenoma detection. Two areas of
      technological interest were considered: (1) optical technologies and (2)
      mechanical technologies. Optical solutions, including FICE, NBI, i-SCAN and high
      definition colonoscopy showed mixed results. In contrast, mechanical advances,
      such as cap-assisted colonoscopy, FUSE, EndoCuff and G-EYETM, showed promise,
      with reported detections rates of up to 69%. However, before definitive
      recommendations can be made for their incorporation into daily practice, further
      studies and comparison trials are required.

PMID- 28454855
TI  - Validation of the abrasion resistance test protocols and performance criteria of
      EN13595: The probability of soft tissue injury to motorcycle riders by abrasion
      resistance of their clothing.
AB  - INTRODUCTION: Motorcyclists represent an increasing proportion of road users
      globally and are increasingly represented in crash statistics. Soft tissue
      injuries are the most common type of injuries to crashed motorcyclists. These
      injuries can be prevented through the use of protective clothing designed for
      motorcycle use. However, the quality of such clothing is not controlled in many
      countries around the world. A European Standard was developed to assess the
      performance of clothing but as this is not mandatory, clothing certified to this
      Standard is difficult to obtain. Given the importance of this Standard, and that
      it has been validated only once, further validation work is required. METHODS: In
      depth crash investigation data were used to investigate the relationship between
      the abrasion resistance performance of clothing and real-world injury outcome.
      Clothing was collected from riders who crashed on public roads in Sydney and
      Newcastle, Australia. This clothing was tested according to the EU Standard and
      the time to hole was recorded. Hospital medical records were reviewed and the
      association between a rider suffering a soft tissue injury and the time-to-hole
      for the garment was examined. RESULTS: The probability of soft tissue injury for
      Level 1 Standard garments was between 40-60%, but more than 60% of garments
      tested failed to meet the minimum requirement. CONCLUSIONS: The findings of this
      study provide qualified support for the Standard, with a marginal association
      between time-to-hole and injury being found. PRACTICAL IMPLICATIONS: This work
      supports the need for improved safety performance and an increased number of high
      performing garments being available to motorcyclists.

PMID- 28454856
TI  - Safety impacts of bicycle infrastructure: A critical review.
AB  - PROBLEM AND METHOD: This paper takes a critical look at the present state of
      bicycle infrastructure treatment safety research, highlighting data needs. Safety
      literature relating to 22 bicycle treatments is examined, including findings,
      study methodologies, and data sources used in the studies. Some preliminary
      conclusions related to research efficacy are drawn from the available data and
      findings in the research. RESULTS AND DISCUSSION: While the current body of
      bicycle safety literature points toward some defensible conclusions regarding the
      safety and effectiveness of certain bicycle treatments, such as bike lanes and
      removal of on-street parking, the vast majority treatments are still in need of
      rigorous research. Fundamental questions arise regarding appropriate exposure
      measures, crash measures, and crash data sources. PRACTICAL APPLICATIONS: This
      research will aid transportation departments with regard to decisions about
      bicycle infrastructure and guide future research efforts toward understanding
      safety impacts of bicycle infrastructure.

PMID- 28454857
TI  - Organizational culture and a safety-conscious work environment: The mediating
      role of employee communication satisfaction.
AB  - INTRODUCTION: A safety-conscious work environment allows high-reliability
      organizations to be proactive regarding safety and enables employees to feel free
      to report any concern without fear of retaliation. Currently, research on the
      antecedents to safety-conscious work environments is scarce. METHOD: Structural
      equation modeling was applied to test the mediating role of employee
      communication satisfaction in the relationship between constructive culture and a
      safety-conscious work environment in several nuclear power plants. RESULTS:
      Employee communication satisfaction partially mediated the positive relationships
      between a constructive culture and a safety-conscious work environment.
      CONCLUSIONS: Constructive cultures in which cooperation, supportive
      relationships, individual growth and high performance are encouraged facilitate
      the establishment of a safety-conscious work environment. This influence is
      partially explained by increased employee communication satisfaction. PRACTICAL
      APPLICATION: Constructive cultures should be encouraged within organizations. In
      addition, managers should promote communication policies and practices that
      support a safety-conscious work environment.

PMID- 28454858
TI  - The relationship between cell phone use and management of driver fatigue: It's
      complicated.
AB  - INTRODUCTION: Voice communication may enhance performance during monotonous,
      potentially fatiguing driving conditions (Atchley & Chan, 2011); however, it is
      unclear whether safety benefits of conversation are outweighed by costs. The
      present study tested whether personalized conversations intended to simulate
      hands-free cell phone conversation may counter objective and subjective fatigue
      effects elicited by vehicle automation. METHOD: A passive fatigue state (Desmond
      & Hancock, 2001), characterized by disengagement from the task, was induced using
      full vehicle automation prior to drivers resuming full control over the driving
      simulator. A conversation was initiated shortly after reversion to manual
      control. During the conversation an emergency event occurred. RESULTS: The
      fatigue manipulation produced greater task disengagement and slower response to
      the emergency event, relative to a control condition. Conversation did not
      mitigate passive fatigue effects; rather, it added worry about matters unrelated
      to the driving task. Conversation moderately improved vehicle control, as
      measured by SDLP, but it failed to counter fatigue-induced slowing of braking in
      response to an emergency event. Finally, conversation appeared to have a hidden
      danger in that it reduced drivers' insights into performance impairments when in
      a state of passive fatigue. CONCLUSIONS: Automation induced passive fatigue,
      indicated by loss of task engagement; yet, simulated cell phone conversation did
      not counter the subjective automation-induced fatigue. Conversation also failed
      to counter objective loss of performance (slower braking speed) resulting from
      automation. Cell phone conversation in passive fatigue states may impair drivers'
      awareness of their performance deficits. Practical applications: Results suggest
      that conversation, even using a hands-free device, may not be a safe way to
      reduce fatigue and increase alertness during transitions from automated to manual
      vehicle control.

PMID- 28454859
TI  - Effects of turning on and off red light cameras on fatal crashes in large U.S.
      cities.
AB  - INTRODUCTION: This study updates estimates of effects of activating red light
      cameras and offers a first look at effects of turning them off. METHOD: Among 117
      large U.S. cities with more than 200,000 residents in 2014, trends in citywide
      per capita rates of fatal red light running crashes and of all fatal crashes at
      signalized intersections were compared between 57 cities that initiated camera
      programs during 1992-2014 and 33 cities without cameras to examine effects of
      activating camera programs. Trends also were compared between 19 cities that
      removed cameras and 31 regionally matched cities with continuous camera programs
      to evaluate effects of terminating camera programs. Because several cities
      removed cameras during 2005-2008 and estimated effects might have been confounded
      by the subsequent economic downturn, primary analyses were limited to the 14
      cities that removed cameras during 2010-2014 and 29 regionally matched cities
      with continuous camera programs. Poisson regression examined the relationship of
      activating and deactivating cameras with fatal crash rates. RESULTS: After
      controlling for temporal trends in annual fatal crash rates, population density,
      and unemployment rates, rates of fatal red light running crashes and of all fatal
      crashes at signalized intersections were 21% and 14% lower, respectively, in
      cities with cameras after cameras were turned on than would have been expected
      without cameras; 30% and 16% higher, respectively, in 14 cities that terminated
      cameras during 2010-2014 after cameras were terminated than expected had cameras
      remained; and 18% and 8% higher, respectively, in all 19 cities that removed
      cameras, but not significantly. CONCLUSIONS: This study adds to the body of
      evidence that red light cameras can reduce the most serious crashes at signalized
      intersections, and is the first to demonstrate that removing cameras increases
      fatal crashes. PRACTICAL APPLICATIONS: Communities thinking about removing
      cameras should consider impacts to safety.

PMID- 28454860
TI  - Assessing drivers' response during automated driver support system failures with
      non-driving tasks.
AB  - INTRODUCTION: With the increase in automated driver support systems, drivers are
      shifting from operating their vehicles to supervising their automation. As a
      result, it is important to understand how drivers interact with these automated
      systems and evaluate their effect on driver responses to safety critical events.
      This study aimed to identify how drivers responded when experiencing a safety
      critical event in automated vehicles while also engaged in non-driving tasks.
      METHOD: In total 48 participants were included in this driving simulator study
      with two levels of automated driving: (a) driving with no automation and (b)
      driving with adaptive cruise control (ACC) and lane keeping (LK) systems engaged;
      and also two levels of a non-driving task (a) watching a movie or (b) no non
      driving task. In addition to driving performance measures, non-driving task
      performance and the mean glance duration for the non-driving task were compared
      between the two levels of automated driving. RESULTS: Drivers using the automated
      systems responded worse than those manually driving in terms of reaction time,
      lane departure duration, and maximum steering wheel angle to an induced lane
      departure event. These results also found that non-driving tasks further impaired
      driver responses to a safety critical event in the automated system condition.
      CONCLUSION: In the automated driving condition, driver responses to the safety
      critical events were slower, especially when engaged in a non-driving task.
      PRACTICAL APPLICATION: Traditional driver performance variables may not
      necessarily effectively and accurately evaluate driver responses to events when
      supervising autonomous vehicle systems. Thus, it is important to develop and use
      appropriate variables to quantify drivers' performance under these conditions.

PMID- 28454861
TI  - Comparative analysis of zonal systems for macro-level crash modeling.
AB  - INTRODUCTION: Macro-level traffic safety analysis has been undertaken at
      different spatial configurations. However, clear guidelines for the appropriate
      zonal system selection for safety analysis are unavailable. In this study, a
      comparative analysis was conducted to determine the optimal zonal system for
      macroscopic crash modeling considering census tracts (CTs), state-wide traffic
      analysis zones (STAZs), and a newly developed traffic-related zone system labeled
      traffic analysis districts (TADs). METHOD: Poisson lognormal models for three
      crash types (i.e., total, severe, and non-motorized mode crashes) are developed
      based on the three zonal systems without and with consideration of spatial
      autocorrelation. The study proposes a method to compare the modeling performance
      of the three types of geographic units at different spatial configurations
      through a grid based framework. Specifically, the study region is partitioned to
      grids of various sizes and the model prediction accuracy of the various macro
      models is considered within these grids of various sizes. RESULTS: These model
      comparison results for all crash types indicated that the models based on TADs
      consistently offer a better performance compared to the others. Besides, the
      models considering spatial autocorrelation outperform the ones that do not
      consider it. CONCLUSIONS: Based on the modeling results and motivation for
      developing the different zonal systems, it is recommended using CTs for socio
      demographic data collection, employing TAZs for transportation demand
      forecasting, and adopting TADs for transportation safety planning. PRACTICAL
      APPLICATIONS: The findings from this study can help practitioners select
      appropriate zonal systems for traffic crash modeling, which leads to develop more
      efficient policies to enhance transportation safety.

PMID- 28454862
TI  - Impact of individual resilience and safety climate on safety performance and
      psychological stress of construction workers: A case study of the Ontario
      construction industry.
AB  - INTRODUCTION: The construction industry has hit a plateau in terms of safety
      performance. Safety climate is regarded as a leading indicator of safety
      performance; however, relatively little safety climate research has been done in
      the Canadian construction industry. Safety climate may be geographically
      sensitive, thus it is necessary to examine how the construct of safety climate is
      defined and used to improve safety performance in different regions. On the other
      hand, more and more attention has been paid to job related stress in the
      construction industry. Previous research proposed that individual resilience may
      be associated with a better safety performance and may help employees manage
      stress. Unfortunately, few empirical research studies have examined this
      hypothesis. This paper aims to examine the role of safety climate and individual
      resilience in safety performance and job stress in the Canadian construction
      industry. METHOD: The research was based on 837 surveys collected in Ontario
      between June 2015 and June 2016. Structural equation modeling (SEM) techniques
      were used to explore the impact of individual resilience and safety climate on
      physical safety outcomes and on psychological stress among construction workers.
      RESULTS: The results show that safety climate not only affected construction
      workers' safety performance but also indirectly affected their psychological
      stress. In addition, it was found that individual resilience had a direct
      negative impact on psychological stress but had no impact on physical safety
      outcomes. CONCLUSIONS: These findings highlight the roles of both organizational
      and individual factors in individual safety performance and in psychological well
      being. PRACTICAL APPLICATIONS: Construction organizations need to not only
      monitor employees' safety performance, but also to assess their employees'
      psychological well-being. Promoting a positive safety climate together with
      developing training programs focusing on improving employees' psychological
      health - especially post-trauma psychological health - can improve the safety
      performance of an organization.

PMID- 28454863
TI  - Distracting behaviors among teenagers and young, middle-aged, and older adult
      drivers when driving without and with warnings from an integrated vehicle safety
      system.
AB  - INTRODUCTION: Negative reinforcement from crash warnings may reduce the
      likelihood that drivers engage in distracted driving. Alternatively, drivers may
      compensate for the perceived safety benefit of crash warnings by engaging in
      distractions more frequently, especially at higher speeds. The purpose of this
      study was to examine whether warning feedback from an integrated vehicle-based
      safety system affected the likelihood that various secondary behaviors were
      present among drivers ages 16-17, 20-30, 40-50, and 60-70. METHOD: Participants
      drove an instrumented sedan with various collision warning systems for an
      extended period. Ten 5-second video clips were randomly sampled from driving
      periods at speeds above 25mph and below 5mph each week for each driver and coded
      for the presence of 11 secondary behaviors. RESULTS: At least one secondary
      behavior was present in 46% of video clips; conversing with a passenger (17%),
      personal grooming (9%), and cellphone conversation (6%) were the most common. The
      likelihood that at least one secondary behavior was present was not significantly
      different during periods when drivers received warnings relative to periods
      without warnings. At least one secondary behavior was 21% more likely to be
      present at speeds below 5mph relative to speeds above 25mph; however, the effect
      of vehicle speed was not significantly affected by warning presence. Separate
      models for each of the five most common secondary behaviors also indicated that
      warnings had no significant effect on the likelihood that each behavior was
      present. CONCLUSIONS: Collision warnings were not associated with significant
      increases or decreases in the overall likelihood that teen and adult drivers
      engaged in secondary behaviors or the likelihood of the behaviors at speeds above
      25mph or below 5mph. PRACTICAL APPLICATIONS: There was no evidence that forward
      collision warning and other technologies like those in this study will increase
      or decrease distracted driving.

PMID- 28454864
TI  - The relationship between patient safety climate and occupational safety climate
      in healthcare - A multi-level investigation.
AB  - INTRODUCTION: Patient safety climate/culture is attracting increasing research
      interest, but there is little research on its relation with organizational
      climates regarding other target domains. The aim of this study was to investigate
      the relationship between patient safety climate and occupational safety climate
      in healthcare. METHOD: The climates were assessed using two questionnaires:
      Hospital Survey on Patient Safety Culture and Nordic Occupational Safety Climate
      Questionnaire. The final sample consisted of 1154 nurses, 886 assistant nurses,
      and 324 physicians, organized in 150 work units, within hospitals (117units),
      primary healthcare (5units) and elderly care (28units) in western Sweden, which
      represented 56% of the original sample contacted. RESULTS: Within each type of
      safety climate, two global dimensions were confirmed in a higher order factor
      analysis; one with an external focus relative the own unit, and one with an
      internal focus. Two methods were used to estimate the covariation between the
      global climate dimensions, in order to minimize the influence of bias from common
      method variance. First multilevel analysis was used for partitioning variances
      and covariances in a within unit part (individual level) and a between unit part
      (unit level). Second, a split sample technique was used to calculate unit level
      correlations based on aggregated observations from different respondents. Both
      methods showed associations similar in strength between the patient safety
      climate and the occupational safety climate domains. CONCLUSIONS: The results
      indicated that patient safety climate and occupational safety climate are
      strongly positively related at the unit level, and that the same organizational
      processes may be important for the development of both types of organizational
      climate. PRACTICAL APPLICATIONS: Safety improvement interventions should not be
      separated in different organizational processes, but be planned so that both
      patient safety and staff safety are considered concomitantly.

PMID- 28454865
TI  - The impact of the 2007 graduated driver licensing law in Massachusetts on the
      rate of citations and licensing in teenage drivers.
AB  - OBJECTIVE: We recently demonstrated that the 2007 Massachusetts Graduated Driving
      Licensing (GDL) law decreased the rate of motor vehicle crashes in teenage
      drivers. To better understand this decrease, we sought to examine the law's
      impact on the issuance of driving licenses and traffic citations to teenage
      drivers. METHODS: Citation and license data were obtained from the Massachusetts
      Department of Transportation. Census data were obtained from the Census Data
      Center. Two study periods were defined: pre-GDL (2002-2006) and post-GDL (2007
      2012). Two populations were defined: the study population (aged 16-17) and the
      control population (aged 25-29). The rates of licenses per population were
      compared pre- vs. post-GDL for the study group. The numbers of total, state, and
      local citations per population were compared pre- vs. post-GDL for both
      populations. A sensitivity analysis was performed for the rates of citations
      using licenses issued as a denominator. RESULTS: While licenses per population
      obtained by the study group decreased over the entire period, there was no change
      in the rate of decrease per year pre- vs. post-GDL (2.0% vs. 1.4%; p=0.6392). In
      the study population, total, state, and local citations decreased post-GDL (17.8%
      vs. 8.1%, p<0.0001; 3.7% vs. 2.2%, p<0.0001; 14.1% vs. 5.8%, p<0.0001,
      respectively). In the control group, total and state citations did not change
      (26.7% vs. 23.9%, p=0.3606; 9.2% vs. 10.2%, p=0.3404, respectively), and local
      citations decreased (17.5% vs. 13.7%, p=0.0389). The rates of decrease per year
      for total, state, and local citations were significantly greater in the study
      population compared with control (p<0.0001, p=0.0002, p<0.0001, respectively).
      CONCLUSIONS: The 2007 GDL law in Massachusetts was associated with fewer traffic
      citations without a change in the rate of licenses issued to teenagers. These
      findings suggest that 2007 GDL may be improving driving habits as opposed to
      motivating teenagers to delay the issuing of licenses.

PMID- 28454866
TI  - How do older adult drivers self-regulate? Characteristics of self-regulation
      classes defined by latent class analysis.
AB  - PROBLEM: Motor-vehicle crashes were the second leading cause of injury death for
      adults aged 65-84years in 2014. Some older drivers choose to self-regulate their
      driving to maintain mobility while reducing driving risk, yet the process remains
      poorly understood. METHODS: Data from 729 older adults (aged >=60years) who
      joined an older adult ride service program between April 1, 2010 and November 8,
      2013 were analyzed to define and describe classes of driving self-regulation.
      Latent class analysis was employed to characterize older adult driving self
      regulation classes using driving frequency and avoidance of seven driving
      situations. Logistic regression was used to explore associations between
      characteristics affecting mobility and self-regulation class. RESULTS: Three
      classes were identified (low, medium, and high self-regulation). High self
      regulating participants reported the highest proportion of always avoiding seven
      risky driving situations and the lowest driving frequency followed by medium and
      low self-regulators. Those who were female, aged 80years or older, visually
      impaired, assistive device users, and those with special health needs were more
      likely to be high self-regulating compared with low self-regulating. CONCLUSIONS
      AND PRACTICAL APPLICATIONS: Avoidance of certain driving situations and weekly
      driving frequency are valid indicators for describing driving self-regulation
      classes in older adults. Understanding the unique characteristics and mobility
      limitations of each class can guide optimal transportation strategies for older
      adults.

PMID- 28454867
TI  - A review of CDC's Web-based Injury Statistics Query and Reporting System
      (WISQARSTM): Planning for the future of injury surveillance.
AB  - INTRODUCTION: The Centers for Disease Control and Prevention (CDC) developed the
      Web-based Injury Statistics Query and Reporting System (WISQARSTM) to meet the
      data needs of injury practitioners. In 2015, CDC completed a Portfolio Review of
      this system to inform its future development. METHODS: Evaluation questions
      addressed utilization, technology and innovation, data sources, and tools and
      training. Data were collected through environmental scans, a review of peer
      reviewed and grey literature, a web search, and stakeholder interviews. RESULTS:
      Review findings led to specific recommendations for each evaluation question.
      RESPONSE: CDC reviewed each recommendation and initiated several enhancements
      that will improve the ability of injury prevention practitioners to leverage
      these data, better make sense of query results, and incorporate findings and key
      messages into prevention practices.

PMID- 28454868
TI  - Brake reactions of distracted drivers to pedestrian Forward Collision Warning
      systems.
AB  - INTRODUCTION: Forward Collision Warning (FCW) can be effective in directing
      driver attention towards a conflict and thereby aid in preventing or mitigating
      collisions. FCW systems aiming at pedestrian protection have been introduced onto
      the market, yet an assessment of their safety benefits depends on the accurate
      modeling of driver reactions when the system is activated. This study contributes
      by quantifying brake reaction time and brake behavior (deceleration levels and
      jerk) to compare the effectiveness of an audio-visual warning only, an added
      haptic brake pulse warning, and an added Head-Up Display in reducing the
      frequency of collisions with pedestrians. Further, this study provides a detailed
      data set suited for the design of assessment methods for car-to-pedestrian FCW
      systems. METHOD: Brake response characteristics were measured for heavily
      distracted drivers who were subjected to a single FCW event in a high-fidelity
      driving simulator. The drivers maintained a self-regulated speed of 30km/h in an
      urban area, with gaze direction diverted from the forward roadway by a secondary
      task. RESULTS: Collision rates and brake reaction times differed significantly
      across FCW settings. Brake pulse warnings resulted in the lowest number of
      collisions and the shortest brake reaction times (mean 0.8s, SD 0.29s). Brake
      jerk and deceleration were independent of warning type. Ninety percent of drivers
      exceeded a maximum deceleration of 3.6m/s2 and a jerk of 5.3m/s3. CONCLUSIONS:
      Brake pulse warning was the most effective FCW interface for preventing
      collisions. In addition, this study presents the data required for driver
      modeling for car-to-pedestrian FCW similar to Euro NCAP's 2015 car-to-car FCW
      assessment. Practical applications: Vehicle manufacturers should consider the
      introduction of brake pulse warnings to their FCW systems. Euro NCAP could
      introduce an assessment that quantifies the safety benefits of pedestrian FCW
      systems and thereby aid the proliferation of effective systems.

PMID- 28454869
TI  - Hierarchical ordered model for injury severity of pedestrian crashes in South
      Korea.
AB  - INTRODUCTION: The high percentage of fatalities in pedestrian-involved crashes is
      a critical social problem. The purpose of this study is to investigate factors
      influencing injury severity in pedestrian crashes by examining the demographic
      and socioeconomic characteristics of the regions where crashes occurred. METHOD:
      To understand the correlation between the unobserved characteristics of
      pedestrian crashes in a defined region, we apply a hierarchical ordered model, in
      which we set crash characteristics as lower-level variables and municipality
      characteristics as upper-level. Pedestrian crash data were collected and analyzed
      for a three-year period from 2011 to 2013. The estimation results show the
      statistically significant factors that increase injury severity of pedestrian
      crashes. RESULTS: At the crash level, the factors associated with increased
      severity of pedestrian injury include intoxicated drivers, road-crossing
      pedestrians, elderly pedestrians, heavy vehicles, wide roads, darkness, and fog.
      At the municipality level, municipalities with low population density, lower
      level of financial independence, fewer doctors, and a higher percentage of
      elderly residents experience more severe pedestrian crashes. Municipalities
      ranked as having the top 10% pedestrian fatality rate (fatalities per 100,000
      residents) have rates 7.4 times higher than municipalities with the lowest 10%
      rate of fatalities. Their demographic and socioeconomic characteristics also have
      significant differences. The proposed model accounts for a 7% unexplained
      variation in injury severity outcomes between the municipalities where crashes
      occurred. CONCLUSION: To enhance the safety of vulnerable pedestrians,
      considerable investments of time and effort in pedestrian safety facilities and
      zones should be made. More certain and severe punishments should be also given
      for the traffic violations that increase injury severity of pedestrian crashes.
      Furthermore, central and local governments should play a cooperative role to
      reduce pedestrian fatalities. Practical applications: Based on our study results,
      we suggest policy directions to enhance pedestrian safety.

PMID- 28454870
TI  - Temporary jobs and the severity of workplace accidents.
AB  - INTRODUCTION: From the point of view of workplace safety, it is important to know
      whether having a temporary job has an effect on the severity of workplace
      accidents. We present an empirical analysis on the severity of workplace
      accidents by type of contract. METHOD: We used microdata collected by the Italian
      national institute managing the mandatory insurance against work related
      accidents. We estimated linear models for a measure of the severity of the
      workplace accident. We controlled for time-invariant fixed effects at worker and
      firm levels to disentangle the impact of the type of contract from the spurious
      one induced by unobservables at worker and firm levels. RESULTS: Workers with a
      temporary contract, if subject to a workplace accident, were more likely to be
      confronted with severe injuries than permanent workers. When correcting the
      statistical analysis for injury under-reporting of temporary workers, we found
      that most of, but not all, the effect is driven by the under-reporting bias.
      CONCLUSIONS: The effect of temporary contracts on the injury severity survived
      the inclusion of worker and firm fixed effects and the correction for temporary
      workers' injury under-reporting. This, however, does not exclude the possibility
      that, within firms, the nature of the work may vary between different categories
      of workers. For example, temporary workers might be more likely to be assigned
      dangerous tasks because they might have less bargaining power. PRACTICAL
      IMPLICATIONS: The findings will help in designing public policy effective in
      increasing temporary workers' safety at work and limiting their injury under
      reporting.

PMID- 28454871
TI  - Time of day effects on railroad roadway worker injury risk.
AB  - INTRODUCTION: The purpose of this study is to examine how time of day affects
      injury risk of railroad maintenance of way employees and signalmen (roadway
      workers). Railroads reported 15,654 serious roadway worker injuries between 1997
      and 2014. Roadway workers primarily work outdoors on or near railroad tracks and
      frequently encounter hazardous conditions. To avoid closing an active rail line
      during peak hours, railroads sometimes require roadway workers to work at night.
      Previous studies of roadway worker injury have not adequately accounted for
      exposure to time of day effects, nor have they investigated the human factors
      issues contributing to roadway worker injury. METHOD: The Federal Railroad
      Administration (FRA) database of injury reports provided data for circadian
      rhythm models of the odds of fatal and nonfatal injuries. The FRA database and
      fatal injury investigation reports also permitted an analysis of the
      circumstances and the human factors issues associated with injuries that occur at
      different times of day. RESULTS: Odds of injury increased during nighttime work.
      The odds of nonfatal injury for both roadway worker crafts rose above 9:1 in the
      early morning hours. The relative odds of a fatal injury also increased
      significantly at night. A human factors analysis suggested that during all three
      shifts most nonfatal injuries involve workload, but workload was not identified
      as a factor in fatal injuries. CONCLUSIONS: Nighttime work is more hazardous for
      roadway workers than daytime work. Several factors related to fatigue and other
      conditions appear to increase the risk of injury during the outdoor, nighttime
      work required of roadway workers. PRACTICAL APPLICATION: For practical reasons,
      nighttime roadway work is sometimes unavoidable. Therefore, new practices for
      nighttime work must be developed to adequately address fatigue and protect
      roadway workers from harm.

PMID- 28454872
TI  - Effects of an integrated collision warning system on teenage driver behavior.
AB  - INTRODUCTION: Crash warning systems have been shown to provide safety benefits,
      but no studies have examined how teenagers respond. This study sought to find out
      whether young, inexperienced drivers change behavior in response to warnings.
      METHODS: Forty 16-17 year-olds drove an instrumented vehicle equipped with a
      system that warned for lane departures and potential rear-end and lane
      change/merge crashes. Participants were randomly assigned to experimental or
      control groups, and their driving was monitored for 14weeks during 2011-12. For
      the experimental group, this included a treatment period, when crash alerts were
      received by drivers, and baseline and post-treatment periods, when warnings were
      recorded but not received. The control group never received warnings. Data were
      analyzed to determine whether warnings were associated with changes in driving
      behavior. RESULTS: A total of 15,039 trips were analyzed. Lane drifts accounted
      for 73% of warnings. Forward collision warning rates doubled for all drivers
      during the treatment period and continued at an increased rate post-treatment.
      This was likely a result of the fact that, as time went on, all drivers spent
      more time following vehicles at close distances. Receiving alerts was associated
      with effects on following and lane-changing behavior, including more time spent
      following at close distances (17%), fewer lateral drifts (37%) and fewer
      unsignaled lane changes (80%). Receiving warnings wasn't associated with an
      increased likelihood of engaging in secondary tasks. CONCLUSIONS: Warning systems
      may result in improved lane-keeping and turn-signal behaviors by novice drivers,
      but there is some indication they may result in more close-following behaviors.
      PRACTICAL APPLICATIONS: There is some evidence that lane departure warning may
      improve turn-signal use for young drivers. While there is no evidence of safety
      benefits from the other types of warnings, there is some evidence of an increase
      in close-following behavior but no increase in secondary tasks due to the
      presence of those capabilities.

PMID- 28454873
TI  - Predicting workers' compensation claims and disciplinary actions using
      SecureFit(r): Further support for integrative models of workplace safety.
AB  - INTRODUCTION: A growing body of applied research has identified certain
      psychological traits that are predictive of worker safety. However, most of these
      studies suffer from an overreliance on common method bias caused by self-report
      measures of both: (a) personal factors such as personality traits; and (b)
      outcomes such as safety behaviors and injuries. METHOD: This study utilized
      archival data from 796 employees at a large U.S. automobile manufacturer. Data
      were gathered on a pre-employment assessment, SecureFit(r), that measured key
      personality characteristics such as conscientiousness, locus of control, and risk
      taking. In addition, objective measures of workers' compensation claims and
      disciplinary actions were also gathered. RESULTS: The results indicated that
      disciplinary actions and workers' compensation claims were strongly correlated.
      It also demonstrated that the pre-employment assessment was able to predict both
      disciplinary actions and workers' compensation claims up to 12months in the
      future. Screening out just 8% of the applicant sample using the assessment would
      have resulted in a 35% reduction in disciplinary actions and 46% in workers'
      compensation claims, respectively. CONCLUSIONS: The study found a very strong
      relationship between counterproductive work behaviors (CWBs), such as not
      following rules, and workers' compensation claims. It also found a strong
      relationship between a combination of personality traits that have been shown to
      be associated with both variables, although the current study was able to
      demonstrate that relationship with objective measure of both variables. PRACTICAL
      APPLICATIONS: Individuals who receive disciplinary actions for things such as not
      following rules, not coming to work on time, etc. are significantly more likely
      to also be involved in serious safety incidents, and vice versa. Identifying
      those individuals early on in the hiring process and screening them out can
      significantly reduce the number of CWBs as well as workers' compensation claims.

PMID- 28454874
TI  - Raising the speed limit from 75 to 80mph on Utah rural interstates: Effects on
      vehicle speeds and speed variance.
AB  - INTRODUCTION: In November 2010 and October 2013, Utah increased speed limits on
      sections of rural interstates from 75 to 80mph. Effects on vehicle speeds and
      speed variance were examined. METHODS: Speeds were measured in May 2010 and May
      2014 within the new 80mph zones, and at a nearby spillover site and at more
      distant control sites where speed limits remained 75mph. Log-linear regression
      models estimated percentage changes in speed variance and mean speeds for
      passenger vehicles and large trucks associated with the speed limit increase.
      Logistic regression models estimated effects on the probability of passenger
      vehicles exceeding 80, 85, or 90mph and large trucks exceeding 80mph. RESULTS:
      Within the 80mph zones and at the spillover location in 2014, mean passenger
      vehicle speeds were significantly higher (4.1% and 3.5%, respectively), as were
      the probabilities that passenger vehicles exceeded 80mph (122.3% and 88.5%,
      respectively), than would have been expected without the speed limit increase.
      Probabilities that passenger vehicles exceeded 85 and 90mph were non
      significantly higher than expected within the 80mph zones. For large trucks, the
      mean speed and probability of exceeding 80mph were higher than expected within
      the 80mph zones. Only the increase in mean speed was significant. Raising the
      speed limit was associated with non-significant increases in speed variance.
      CONCLUSIONS: The study adds to the wealth of evidence that increasing speed
      limits leads to higher travel speeds and an increased probability of exceeding
      the new speed limit. Results moreover contradict the claim that increasing speed
      limits reduces speed variance. PRACTICAL APPLICATIONS: Although the estimated
      increases in mean vehicle speeds may appear modest, prior research suggests such
      increases would be associated with substantial increases in fatal or injury
      crashes. This should be considered by lawmakers considering increasing speed
      limits.

PMID- 28454875
TI  - Incorporating real-time traffic and weather data to explore road accident
      likelihood and severity in urban arterials.
AB  - INTRODUCTION: The effective treatment of road accidents and thus the enhancement
      of road safety is a major concern to societies due to the losses in human lives
      and the economic and social costs. The investigation of road accident likelihood
      and severity by utilizing real-time traffic and weather data has recently
      received significant attention by researchers. However, collected data mainly
      stem from freeways and expressways. Consequently, the aim of the present paper is
      to add to the current knowledge by investigating accident likelihood and severity
      by exploiting real-time traffic and weather data collected from urban arterials
      in Athens, Greece. METHOD: Random Forests (RF) are firstly applied for
      preliminary analysis purposes. More specifically, it is aimed to rank candidate
      variables according to their relevant importance and provide a first insight on
      the potential significant variables. Then, Bayesian logistic regression as well
      finite mixture and mixed effects logit models are applied to further explore
      factors associated with accident likelihood and severity respectively. RESULTS:
      Regarding accident likelihood, the Bayesian logistic regression showed that
      variations in traffic significantly influence accident occurrence. On the other
      hand, accident severity analysis revealed a generally mixed influence of traffic
      variations on accident severity, although international literature states that
      traffic variations increase severity. Lastly, weather parameters did not find to
      have a direct influence on accident likelihood or severity. CONCLUSIONS: The
      study added to the current knowledge by incorporating real-time traffic and
      weather data from urban arterials to investigate accident occurrence and accident
      severity mechanisms. PRACTICAL APPLICATION: The identification of risk factors
      can lead to the development of effective traffic management strategies to reduce
      accident occurrence and severity of injuries in urban arterials.

PMID- 28454876
TI  - Developing leading indicators from OHS management audit data: Determining the
      measurement properties of audit data from the field.
AB  - INTRODUCTION: OHS management audits are one means of obtaining data that may
      serve as leading indicators. The measurement properties of such data are
      therefore important. This study used data from Workwell audit program in Ontario,
      a Canadian province. The audit instrument consisted of 122 items related to 17
      OHS management elements. The study sought answers regarding (a) the ability of
      audit-based scores to predict workers' compensation claims outcomes, (b)
      structural characteristics of the data in relation to the organization of the
      audit instrument, and (c) internal consistency of items within audit elements.
      METHOD: The sample consisted of audit and claims data from 1240 unique firms that
      had completed one or two OHS management audits during 2007-2010. Predictors
      derived from the audit results were used in multivariable negative binomial
      regression modeling of workers' compensation claims outcomes. Confirmatory factor
      analyses were used to examine the instrument's structural characteristics. Kuder
      Richardson coefficients of internal consistency were calculated for each audit
      element. RESULTS: The ability of audit scores to predict subsequent claims data
      could not be established. Factor analysis supported the audit instrument's
      element-based structure. KR-20 values were high (>=0.83). CONCLUSIONS: The
      Workwell audit data display structural validity and high internal consistency,
      but not, to date, construct validity, since the audit scores are generally not
      predictive of subsequent firm claim experience. Audit scores should not be
      treated as leading indicators of workplace OHS performance without supporting
      empirical data. PRACTICAL APPLICATIONS: Analyses of the measurement properties of
      audit data can inform decisionmakers about the operation of an audit program,
      possible future directions in audit instrument development, and the appropriate
      use of audit data. In particular, decision-makers should be cautious in their use
      of audit scores as leading indicators, in the absence of supporting empirical
      data.

PMID- 28454877
TI  - Ancient bacterial endosymbionts of insects: Genomes as sources of insight and
      springboards for inquiry.
AB  - Ancient associations between insects and bacteria provide models to study
      intimate host-microbe interactions. Currently, a wealth of genome sequence data
      for long-term, obligately intracellular (primary) endosymbionts of insects
      reveals profound genomic consequences of this specialized bacterial lifestyle.
      Those consequences include severe genome reduction and extreme base compositions.
      This minireview highlights the utility of genome sequence data to understand how,
      and why, endosymbionts have been pushed to such extremes, and to illuminate the
      functional consequences of such extensive genome change. While the static
      snapshots provided by individual endosymbiont genomes are valuable, comparative
      analyses of multiple genomes have shed light on evolutionary mechanisms. Namely,
      genome comparisons have told us that selection is important in fine-tuning gene
      content, but at the same time, mutational pressure and genetic drift contribute
      to genome degradation. Examples from Blochmannia, the primary endosymbiont of the
      ant tribe Camponotini, illustrate the value and constraints of genome sequence
      data, and exemplify how genomes can serve as a springboard for further
      comparative and experimental inquiry.

PMID- 28454878
TI  - Salinomycin acts through reducing AKT-dependent thymidylate synthase expression
      to enhance erlotinib-induced cytotoxicity in human lung cancer cells.
AB  - Erlotinib (TarcevaR) is a selective epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor in the treatment of human non-small cell lung cancer
      (NSCLC). Salinomycin, a polyether antibiotic, has been promising a novel
      therapeutic agent for lung cancer, and down-regulated the expression of
      thymidylate synthase (TS) in NSCLC cell lines. Previous study showed that against
      EGFR and TS was strongly synergistic cytotoxicity in NSCLC cells. In this study,
      we showed that erlotinib (1.25-10MUM) treatment down-regulating of TS expression
      in an AKT inactivation manner in two NSCLC cell lines, human lung squamous cell
      carcinoma H1703 and adenocarcinoma H1975 cells. Knockdown of TS using small
      interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002
      enhanced the cytotoxicity and cell growth inhibition of erlotinib. A combination
      of erlotinib and salinomycin resulted in synergistic enhancement of cytotoxicity
      and cell growth inhibition in NSCLC cells, accompanied with reduced protein
      levels of phospho-AKT(Ser473), phospho-AKT(Thr308), and TS. Overexpression of a
      constitutive active AKT (AKT-CA) or Flag-TS expression vector reversed the
      salinomycin and erlotinib-induced synergistic cytotoxicity. Our findings
      suggested that the down-regulation of AKT-mediated TS expression by salinomycin
      enhanced the erlotinib-induced cytotoxicity in NSCLC cells. These results may
      provide a rationale to combine salinomycin with erlotinib for lung cancer
      treatment.

PMID- 28454879
TI  - Expansion of CD26 positive fibroblast population promotes keloid progression.
AB  - BACKGROUND: Keloid is a skin fibrosis disease that characterised by invasive
      growth of fibroblasts and aberrant deposition of extracellular matrix. Studies
      indicated that keloid fibroblasts (KFs) is a class of 'activated' fibroblasts,
      which show accelerated proliferation and excessive extracellular matrix formation
      as compared with normal fibroblasts (NFs). However, the mechanism underlying
      keloid fibroblasts dysfunction is still unknown. OBJECTIVE: To verify CD26
      expression difference between KFs and NFs, and investigate the function of CD26
      positive fibroblasts in keloid progression. METHODS: KFs and NFs were isolated
      from Keloid tissues and normal skin tissues respectively. Flow cytometry was
      performed to isolate CD26+/CD26- fibroblasts from KFs and NFs. Proliferation of
      different fibroblasts were analyzed by CCK8 assay and Ki 67 straining.
      Profibrotic phenotype difference was detected by qRT-PCR, western blot, ELISA and
      immunofluorescence. Scratching experiment and transwell assay were used to assess
      invasion ability of CD26+/CD26- fibroblasts. Diprotin A was used as a CD26
      inhibitor to further investigated the function of CD26 fibroblasts in keloid
      disease. RESULT: CD26 expression was increased in KFs, and the proportion of
      CD26+ fibroblasts was significantly increased in KFs. Cell viability analysis
      showed that CD26+ fibroblasts was more active in proliferation. Furthermore, the
      expression of profibrotic genes were increased in CD26+ fibroblasts, including
      TGF-beta1, IGF-1, IL6, collagen 1, collagen 3 and fibronectin. And meanwhile,
      CD26+ fibroblasts showed stronger invasion ability as compared to CD26-
      fibroblasts. Moreover, Diprotin A significantly suppressed proliferation and
      extracellular matrix secretion of CD26+ fibroblasts isolated from keloid tissues.
      CONCLUSION: Our findings suggest that CD26+ fibroblasts possess proliferation
      advantage in compare to CD26- fibroblasts, and the advantage caused expansion of
      CD26 positive fibroblast population promotes keloid progression.

PMID- 28454880
TI  - Expression of negative immune regulatory molecules, pro-inflammatory chemokine
      and cytokines in immunopathology of ECM developing mice.
AB  - The pathological events in human cerebral malaria are mimicked in the
      experimental cerebral malaria (ECM) in Plasmodium berghei ANKA (PBA)-infected
      C57BL/6 mice. Although previously implied in ECM, the kinetics of cytokines and
      chemokines expression-an essential functional feature for defining causality in
      ECM development-remained untested. Herein, we characterized the
      immunopathological changes and the expression of negative immune regulatory
      molecules, cytokines and chemokines through asymptomatic (3days after infection,
      3dpi), symptomatic (5dpi) and ECM (7dpi) stages in PBA-infected C57BL/6 mice.
      Parasitized RBCs were first detected in brain on 3dpi, edema and tissue
      alterations on 5dpi, and hemorrhages in different areas of brain on 7dpi.
      Increased cerebellar PD-1, CTLA-4 and LAG-3 expression and reduced hippocampal
      CXCL-4 expression on 3dpi were the first observed immunological changes. The
      negative immune regulatory molecules (PD-L1, CTLA-4), cytokines (TNF-alpha, sFAS
      L), and chemokines (CXCL-10, MIP-1beta) transcript levels varied in different
      brain areas in symptomatic and ECM phases. By 5dpi, TNF-alpha, CXCL10 and MIP
      1beta significantly increased in all brain parts studied; IL-1RA in whole brain,
      whereas CXCL4 reduced in hippocampus and cerebrum. By 7dpi, the hippocampal PD-1,
      CXCL4 and CTLA-4 expression decreased but the cerebral, cerebellar and
      hippocampal PD-L1 expression were elevated. TNF-alpha, CXCL10, MIP-1beta, PD-1,
      CTLA-4 and PD-L1 expression were up-regulated in different brain areas. The
      TNFR2, IFN-gamma receptor, Lymphotoxin-beta receptor and sFAS-L transcripts
      significantly increased in brain in ECM. Our data characterize key dynamic
      immunopathological changes in brain to imply relationship to ECM development.

PMID- 28454881
TI  - Prevalence of Leishmania species in rodents: A systematic review and meta
      analysis in Iran.
AB  - Leishmaniasis are diverse group of diseases caused by numerous species of genus
      Leishmania. Herein we have contrived a systematic review and meta-analysis on the
      prevalence of Leishmania species in rodents of Iran. For this purpose, following
      the general methodology recommended for systematic reviews and meta-analysis, six
      English databases (PubMed, Science Direct, Scopus, Ovid, Web of Science and
      Google Scholar) and four Persian databases (Magiran, SID, Iran Doc and Iran
      Medex) were explored during January 1995 till June 2015. Papers were selected
      based on 8 pre-defined inclusion criteria. During the years, a total number of
      4485 different rodents were captured; among which 1291 cases were Leishmania
      positive. The calculated weighted prevalence of Leishmania species in rodents was
      23% (95% CI=18-28). Given geographical zones of Iran, the highest and lowest
      prevalence rate was belonged to North 50% (95% CI=40-61) and West 11% (95% CI=5
      17), respectively. Rhombomys opimus (1766), Meriones lybicus (1258) and Tatera
      indica (488) were the three most abundant captured rodents, while the highest
      prevalence of Leishmania species was observed in Nesokia indica 48% (95% CI=42
      54) and followed by R. opimus 39% (95% CI=30-47). Egger's regression test was
      performed to detect publication bias, which revealed it may not have a
      significant influence on overall weighted prevalence estimate (P=0.317). Meta
      regression analysis demonstrated that there is no significant relationship
      between overall prevalence with sample size (P=0.1) and year of publication
      (P=0.7). The results showed remarkable prevalence of Leishmania species in rodent
      reservoirs. In future, adopting a suitable strategy for control and combat with
      rodents is necessary.

PMID- 28454882
TI  - New frontiers for environmental epidemiology in a changing world.
AB  - BACKGROUND: In the next 25years, transformative changes, in particular the rapid
      pace of technological development and data availability, will require
      environmental epidemiologists to prioritize what should (rather than could) be
      done to most effectively improve population health. OBJECTIVES: In this essay, we
      map out key driving forces that will shape environmental epidemiology in the next
      25years. We also identify how the field should adapt to best take advantage of
      coming opportunities and prepare for challenges. DISCUSSION: Future environmental
      epidemiologists will face a world shaped by longer lifespans but also larger
      burdens of chronic health conditions; shifting populations by region and into
      urban areas; and global environmental change. Rapidly evolving technologies,
      particularly in sensors and OMICs, will present opportunities for the field. How
      should it respond? We argue, the field best adapts to a changing world by
      focusing on healthy aging; evidence gaps, especially in susceptible populations
      and low-income countries; and by developing approaches to better handle
      complexity and more formalized analysis. CONCLUSIONS: Environmental epidemiology
      informing disease prevention will continue to be valuable. However, the field
      must adapt to remain relevant. In particular, the field must ensure that public
      health importance drives research questions, while seizing the opportunities
      presented by new technologies. Environmental epidemiologists of the future will
      require different, refined skills to work effectively across disciplines, ask the
      right questions, and implement appropriate study designs in a data-rich world.

PMID- 28454883
TI  - Treatment of inflammatory bowel disease by leukocytapheresis.
AB  - Studies about leukocytapheresis have emerged with the need of search for
      alternatives to conventional treatment in inflammatory bowel diseases (IBD).
      Leukocytapheresis is a novel non-pharmacologic approach for active ulcerative
      colitis (UC) and Crohn's disease (CD), in which leukocytes are mechanically
      removed from the circulatory system. Patients with active IBD treated with
      leukocytapheresis using a Cellsorba E column between 2012 and 2015, were enrolled
      in Turkey. In our experience, the results of leukocytapheresis therapy in 6
      patients with CD and 20 patients with active UC were overviewed.
      Leukocytapheresis (10 sessions for remission induction therapy, 6 sessions for
      maintenance therapy) was applied to the patients with their concomitant
      medications. Intensive leukocytapheresis (>=4 leukocytapheresis sessions within
      the first 2 weeks) was used in 30% patients with active severe UC. The overall
      clinical remission rate in patients with UC was 80%, and the mucosal healing rate
      was 65%. Patients were followed for an average of 24 months. It was observed that
      clinical remission has continued in 65% of patients with UC. Mild relapse was
      observed in 3 patients with UC during follow up period. In 5 patients with CD
      significant clinical remission was achieved except only one patient. Surgical
      needs were disappeared in 3 patients with obstructive type Crohn's disease.
      Adverse events were seen in only 4.3% of 416 sessions. Any concomitant
      medications did not increase the incidence of adverse events. Our results
      indicate that leukocytapheresis is efficacious in improving remission rates with
      excellent tolerability and safety in patients with IBD.

PMID- 28454884
TI  - Immunoglobulin G levels during collection of large volume plasma for
      fractionation.
AB  - BACKGROUND: There is a need of comprehensive work dealing with the quality of
      plasma for fractionation with respect to the IgG content as today most plasma
      derivates are used to treat patients with immunodeficiencies and autoimmune
      disorders. Therefore, a prospective study was carried out to analyse IgG levels
      before plasmapheresis and every 200ml collected plasma. MATERIALS AND METHODS:
      Fifty-four experienced plasmapheresis donors were recruited for subsequent 850ml
      plasmapheresis using the Aurora Plasmapheresis System. Donors peripheral blood
      counts were analysed before and after plasmapheresis using an electronic counter.
      Total protein, IgG and citrate were measured turbidometrically before, during and
      after apheresis as well as in the plasma product. Furthermore, platelets, red and
      white blood cells were analysed as parameters of product quality. RESULTS: An
      average of 2751+/-247ml blood was processed in 47+/-6min. The collected plasma
      volume was 850+/-1mL and citrate consumption was 177+/-15mL. A continuous drop of
      donors' IgG level was observed during plasmapheresis. The drop was 13% of the IgG
      baseline value at 800mL collected plasma. Total protein, IgG and cell counts of
      the plasma product met current guidelines of plasma for fractionation.
      CONCLUSION: Donors' IgG levels during apheresis showed a steady decrease without
      compromising the quality of plasma product.

PMID- 28454885
TI  - Corrigendum to "Developmental exposure to bisphenol A (BPA) alters sexual
      differentiation in painted turtles (Chrysemys picta)" [Gen. Comp. Endocr. 216
      (2015) 77-85].

PMID- 28454886
TI  - Aortic Arch in Marfan Syndrome Repaired Using the XL-stent.

PMID- 28454887
TI  - Trends in Pulmonary Hypertension Over a Period of 30 Years: Experience From a
      Single Referral Centre.
AB  - INTRODUCTION AND OBJECTIVES: Pulmonary arterial hypertension (PAH) is
      characterized by increased pulmonary vascular resistance, right ventricular
      dysfunction and death. Despite scientific advances, is still associated with high
      morbidity and mortality. The aim is to describe the clinical approach and
      determine the prognostic factors of patients with PAH treated in a national
      reference center over 30 years. METHODS: Three hundred and seventy nine
      consecutive patients with PAH (January 1984 to December 2014) were studied. Were
      divided into 3 periods of time: before 2004, 2004-2009 and 2010-2014. Prognostic
      factors (multivariate analysis) were analyzed for clinical deterioration.
      RESULTS: Median age was 44 years (68.6% women), functional class III-IV: 72%. An
      increase was observed in more complex etiologies in the last period of time:
      Pulmonary venooclusive disease and portopulmonary hypertension. Upfront
      combination therapy significantly increased (5% before 2004 vs 27% after 2010; P
      < .05). Multivariate analysis showed prognostic significance in age, sex,
      etiology and combined clinical variables as they are independent predictors of
      clinical deterioration (P < .05). Survival free from death or transplantation for
      the 1st, 3rd and 5th year was 92.2%, 80.6% and 68.5% respectively. The median
      survival was 9 years (95% confidence interval, 7.532-11.959) CONCLUSIONS: The PAH
      is a heterogeneous and complex disease, the median survival free from death or
      transplantation in our series is 9 years after diagnosis. The structure of a
      multidisciplinary unit PAH must adapt quickly to changes that occur over time
      incorporating new diagnostic and therapeutic techniques.

PMID- 28454888
TI  - Cardiogenic Shock and Cardiac Tamponade in the Context of Influenza A
      Myopericarditis.

PMID- 28454889
TI  - Detection of High-sensitivity Troponin T in Patients With Cardiovascular Risk.

PMID- 28454890
TI  - Plasticity of vagal afferent signaling in the gut.
AB  - Vagal sensory neurons mediate the vago-vagal reflex which, in turn, regulates a
      wide array of gastrointestinal functions including esophageal motility, gastric
      accommodation and pancreatic enzyme secretion. These neurons also transmit
      sensory information from the gut to the central nervous system, which then
      mediates the sensations of nausea, fullness and satiety. Recent research
      indicates that vagal afferent neurons process non-uniform properties and a
      significant degree of plasticity. These properties are important to ensure that
      vagally regulated gastrointestinal functions respond rapidly and appropriately to
      various intrinsic and extrinsic factors. Similar plastic changes in the vagus
      also occur in pathophysiological conditions, such as obesity and diabetes,
      resulting in abnormal gastrointestinal functions. A clear understanding of the
      mechanisms which mediate these events may provide novel therapeutic targets for
      the treatment of gastrointestinal disorders due to vago-vagal pathway
      malfunctions.

PMID- 28454891
TI  - When more is less.

PMID- 28454892
TI  - DNA damage response activation and cell cycle dysregulation in infiltrative
      ameloblastomas: A proposed model for ameloblastoma tumor evolution.

PMID- 28454893
TI  - Transfer of learned category-response associations is modulated by instruction.
AB  - Although instructions often emphasize categories (e.g., odd number->left hand
      response) rather than specific stimuli (e.g., 3->left hand response), learning is
      often interpreted in terms of stimulus-response (S-R) bindings or, less
      frequently, stimulus-classification (S-C) bindings with little attention being
      paid to the importance of category-response (C-R) bindings. In a training
      transfer paradigm designed to investigate the early stages of category learning,
      participants were required to classify stimuli according to the category
      templates presented prior to each block (Experiments 1-4). In some transfer
      blocks the stimuli, categories and/or responses could be novel or repeated from
      the preceding training phase. Learning was assessed by comparing the transfer
      training performance difference across conditions. Participants were able to
      rapidly transfer C-R associations to novel stimuli but evidence of S-C transfer
      was much weaker and S-R transfer was largely limited to conditions where the
      stimulus was classified under the same category. Thus, even though there was some
      evidence that learned S-R and S-C associations contributed to performance,
      learned C-R associations seemed to play a much more important role. In a final
      experiment (Experiment 5) the stimuli themselves were presented prior to each
      block, and the instructions did not mention the category structure. In this
      experiment, the evidence for S-R learning outweighed the evidence for C-R
      learning, indicating the importance of instructions in learning. The implications
      for these findings to the learning, cognitive control, and automaticity
      literatures are discussed.

PMID- 28454894
TI  - The antimalarial drug artemisinin induces an additional, Sod1-supressible anti
      mitochondrial action in yeast.
AB  - The molecular action of artemisinins (ARTs) is not well understood. To determine
      the molecular and cellular basis that might underlie their differential effects
      observed in anti-malarial and anti-cancer studies, we utilized the yeast
      Saccharomyces cerevisiae to examine their toxicity profiles and properties.
      Previously we reported that while both low levels (2-8MUM) of artemisinin (ART)
      and dihydroartemisinin (DHA) partly depolarize the mitochondrial membranes,
      inhibiting yeast growth on non-fermentable media, only DHA at moderate levels
      (such as 40MUM) potently represses yeast growth on fermentable media via a heme
      mediated pathway. Here we show that the lack of toxicity of ART even at high
      levels (200-400MUM) on fermentable medium is due to the presence of Sod1. While
      we expected this normally Sod1-supressed action to be heme-mediated like DHA,
      surprisingly, this toxicity of ART is due to further depolarization of the
      mitochondrial membrane. We also found that for DHA, the Sod1-suppressible anti
      mitochondrial action is hidden by its heme-mediated cytotoxicity, and becomes
      readily noticeable only when the heme-mediated action is compromised and Sod1 is
      inactivated. Based on these findings, we propose that depending on the cell type
      and particular compound, ARTs work via one or more of the three types of
      activities: a Sod1-independent, partial mitochondria-depolarizing action; a Sod1
      suppressible, more severe mitochondria-depolarizing action; and a heme-mediated
      general cytotoxicity. These action properties may underlie the disparities seen
      in the efficacy and toxicity of various ARTs, and additionally suggest it is
      important for researchers to clearly detail the particular compound when
      reporting on the effects of ARTs.

PMID- 28454895
TI  - Sustained attention to objects' motion sharpens position representations:
      Attention to changing position and attention to motion are distinct.
AB  - In tasks where people monitor moving objects, such the multiple object tracking
      task (MOT), observers attempt to keep track of targets as they move amongst
      distracters. The literature is mixed as to whether observers make use of motion
      information to facilitate performance. We sought to address this by two means:
      first by superimposing arrows on objects which varied in their informativeness
      about motion direction and second by asking observers to attend to motion
      direction. Using a position monitoring task, we calculated mean error magnitudes
      as a measure of the precision with which target positions are represented. We
      also calculated perceptual lags versus extrapolated reports, which are the times
      at which positions of targets best match position reports. We find that the
      presence of motion information in the form of superimposed arrows made no
      difference to position report precision nor perceptual lag. However, when we
      explicitly instructed observers to attend to motion, we saw facilitatory effects
      on position reports and in some cases reports that best matched extrapolated
      rather than lagging positions for small set sizes. The results indicate that
      attention to changing positions does not automatically recruit attention to
      motion, showing a dissociation between sustained attention to changing positions
      and attention to motion.

PMID- 28454896
TI  - "Did You Climax or Are You Just Laughing at Me?" Rare Phenomena Associated With
      Orgasm.
AB  - INTRODUCTION: The study of the human orgasm has shown a core set of physiologic
      and psychological symptoms experienced by most individuals. The study of normal
      sheds light on the abnormal and has spotlighted rare physical and psychological
      symptoms experienced by some individuals in association with orgasm. These
      phenomena are rare and, as is typical of rare phenomena, their documentation in
      the medical literature is largely confined to case studies. AIM: To identify peri
      orgasmic phenomena, defined as unusual physical or psychological symptoms
      subjectively experienced by some individuals as part of the orgasm response,
      distinct from the usual or normal orgasm response. METHODS: A list of peri
      orgasmic phenomena was made with help from sexual health colleagues and, using
      this list as a foundation, a literature search was performed of articles
      published in English. MAIN OUTCOME MEASURES: Publications included in this review
      report on physical or psychological phenomena at the time of orgasm that are
      distinct from psychological, whole-body, and genito-pelvic sensations commonly
      experienced at the time of orgasm. Cases of physical symptoms related to the
      physiology of sexual intercourse and not specifically to orgasm were excluded.
      RESULTS: Case studies of peri-orgasmic phenomena were reviewed, including cases
      describing cataplexy (weakness), crying, dysorgasmia, dysphoria, facial and/or
      ear pain, foot pain, headache, pruritus, laughter, panic attack, post-orgasm
      illness syndrome, seizures, and sneezing. CONCLUSION: The literature review
      confirms the existence of diverse and frequently replicated peri-orgasmic
      phenomena. The value of case studies is in the collection and recording of
      observations so that hypotheses can be formed about the observed phenomena.
      Accordingly, this review could inspire further research on the neurophysiologic
      mechanisms of orgasm. Reinert AE, Simon JA. "Did You Climax or Are You Just
      Laughing at Me?" Rare Phenomena Associated With Orgasm. Sex Med Rev 2017;5:275
      281.

PMID- 28454897
TI  - Collagenase Clostridium Histolyticum in the Treatment of Urologic Disease:
      Current and Future Impact.
AB  - INTRODUCTION: Peyronie's disease (PD) is a connective tissue disorder resulting
      in the abnormal accumulation of type I to III collagen, fibrin, and disorganized
      elastic fibers in the tunica albuginea of the penis. Many medical and non
      pharmacologic modalities have been used in the treatment of PD; however, these
      approaches have proved largely ineffective, with surgery being the only
      definitive treatment. Intralesional injection of collagenase Clostridium
      histolyticum (CCH) has recently become the gold standard for minimally invasive
      treatment of PD, and studies have suggested the role of CCH could expand to the
      treatment of other urologic conditions such as urethral stricture disease. AIM:
      To provide an update on available data on the use of CCH in the treatment of PD
      and other urologic conditions. METHODS: Comprehensive review of recent clinical
      trials and in vivo studies that examined the safety and efficacy of CCH in
      urologic disease. MAIN OUTCOME MEASURES: Assessing the efficacy of CCH in the
      management of PD as determined by improvement in the severity of penile fibrosis,
      curvature deformity, and pain. RESULTS: Several well-designed clinical trials
      have demonstrated the efficacy and tolerability of CCH in the treatment of PD.
      CCH has demonstrated significant decreases in penile curvature and plaque
      consistency and improvements in patient satisfaction. Treatment durability and
      long-term adverse effects are still being assessed; however, outcomes of PD
      management with CCH continue to replicate the results obtained during the IMPRESS
      clinical trials. Preliminary studies support the premise that CCH can modify
      disease progression in patients with acute-phase PD. Furthermore, one in vivo
      study showed that CCH also could be applied to urethral stricture disease without
      serious adverse complications. CONCLUSION: CCH continues to be the mainstay for
      non-surgical management of stable-phase PD. However, its role in the treatment of
      acute-phase PD, PD with ventral plaques, and urethral stricture disease could
      expand in the coming years. Gabrielson AT, Spitz JT, Hellstrom WJG. Collagenase
      Clostridium Histolyticum in the Treatment of Urologic Disease: Current and Future
      Impact. Sex Med Rev 2018;6:143-156.

PMID- 28454898
TI  - Prospective study of filtering blebs after XEN45 surgery.
AB  - OBJECTIVE: To qualitatively analyse the evolution of filtering blebs after XEN
      surgery, by using anterior segment optical coherence tomography (AS-OCT).
      METHODS: A prospective study was performed on filtering blebs of 30 eyes with
      cataracts and glaucoma, surgically operated on using phacoemulsification and
      XEN45 implantation (PHACO-XEN). AS-OCT was used to analyse bleb morphology and
      reflectivity at 3, 6, and 12 months after surgery. Functionality was studied
      considering an intraocular pressure (IOP)<=18mmHg without antihypertensive
      medication. RESULTS: The IOP enabled the blebs to be classified into non
      functional: flat (6.67%) and encapsulated (3.33%); and functional (90%), which
      were then divide by their morphology into cystic (5/27), diffuse (2/27), and
      layered (20/27). Cystic types had a mean IOP of 12.8, 12.6, and 14.0mmHg at 3, 6
      and 12 months, respectively. In the diffuse type, the mean IOP was 13.0, 11.5 and
      13.0mmHg at 3, 6 and 12 months, respectively. In the layers pattern the mean IOP
      was 14.45, 14.55 and 14.8mmHg at 3, 6 and 12 months respectively. The percentage
      of blebs with high reflectivity was 48.15%, 62.96%, and 77.78%, at 3, 6 and 12
      months, with a mean IOP of 14.23, 14.59, and 15.14mmHg in each time period,
      respectively. CONCLUSION: AS-OCT could be a good predictor of bleb functionality
      in PHACO-XEN surgery. Those with a cystic pattern or low reflectivity seem to
      have better post-operative success. Nevertheless, more long-term studies are
      required.

PMID- 28454899
TI  - Population-Level Outcomes with a 2-Step Approach for Gestational Diabetes
      Screening and Diagnosis.
AB  - OBJECTIVES: To examine outcomes associated with alternative glucose thresholds in
      a 2-step approach for screening and diagnosing gestational diabetes mellitus
      (GDM). METHODS: We studied 178,527 pregnancies between 2008 and 2012 in Alberta,
      Canada. They were categorized retrospectively as normal 50 g screen (n=144,191);
      normal 75 g oral glucose tolerance test (OGTT) (n=21,248); abnormal at glucose
      thresholds suggested by the International Association of Diabetes and Pregnancy
      Group (IADPSG) (HAPO 1.75, n=4308); abnormal at glucose thresholds associated
      with an odds ratio of 2.0 for adverse events in the Hyperglycemia and Adverse
      Pregnancy Outcomes (HAPO) study. This latter group, which would have been treated
      for GDM based on customary care, was further divided into those with 1 (HAPO 2-1
      n=5528) or 2 or more abnormal glucose values (HAPO 2-2 n=3252). Main outcomes
      were large for gestational age (LGA), induced labour and Cesarean-section rates.
      RESULTS: LGA rates were 8.2%, 10.5%, 14.2%, 11.8% and 16.5% among normal 50 g,
      normal 75 g OGTT, HAPO 1.75, HAPO 2-1, and HAPO 2-2 groups, respectively. Labour
      induction and caesarean-section rates were 29.6% and 36.2% in the IADPSG, 38.2%
      and 36.8% in the HAPO 2-1 group, and 42.3% and 41.1% in the HAPO 2-2 groups,
      respectively. Excessive maternal weight (>=91 kg) was associated with a higher
      risk for all adverse outcomes. CONCLUSIONS: The 2-step approach effectively
      identifies pregnancies at low risk for adverse outcomes. Labelling influences
      induction practice. Any glucose intolerance increases risk for adverse outcomes,
      and pregnancies with highest (2 or higher) abnormal glucose values remain at
      greatest risk. Further research is needed to determine whether glycemic
      thresholds for GDM diagnosis should incorporate information about maternal
      weight.

PMID- 28454900
TI  - DBH: A de Bruijn graph-based heuristic method for clustering large-scale 16S rRNA
      sequences into OTUs.
AB  - Recent sequencing revolution driven by high-throughput technologies has led to
      rapid accumulation of 16S rRNA sequences for microbial communities. Clustering
      short sequences into operational taxonomic units (OTUs) is an initial crucial
      process in analyzing metagenomic data. Although many heuristic methods have been
      proposed for OTU inferences with low computational complexity, they just select
      one sequence as the seed for each cluster and the results are sensitive to the
      selected sequences that represent the clusters. To address this issue, we present
      a de Bruijn graph-based heuristic clustering method (DBH) for clustering massive
      16S rRNA sequences into OTUs by introducing a novel seed selection strategy and
      greedy clustering approach. Compared with existing widely used methods on several
      simulated and real-life metagenomic datasets, the results show that DBH has
      higher clustering performance and low memory usage, facilitating the
      overestimation of OTUs number. DBH is more effective to handle large-scale
      metagenomic datasets. The DBH software can be freely downloaded from
      https://github.com/nwpu134/DBH.git for academic users.

PMID- 28454901
TI  - A computational model for predicting integrase catalytic domain of retrovirus.
AB  - Integrase catalytic domain (ICD) is an essential part in the retrovirus for
      integration reaction, which enables its newly synthesized DNA to be incorporated
      into the DNA of infected cells. Owing to the crucial role of ICD for the
      retroviral replication and the absence of an equivalent of integrase in host
      cells, it is comprehensible that ICD is a promising drug target for therapeutic
      intervention. However, annotated ICDs in UniProtKB database have still been
      insufficient for a good understanding of their statistical characteristics so
      far. Accordingly, it is of great importance to put forward a computational ICD
      model in this work to annotate these domains in the retroviruses. The proposed
      model then discovered 11,660 new putative ICDs after scanning sequences without
      ICD annotations. Subsequently in order to provide much confidence in ICD
      prediction, it was tested under different cross-validation methods, compared with
      other database search tools, and verified on independent datasets. Furthermore,
      an evolutionary analysis performed on the annotated ICDs of retroviruses revealed
      a tight connection between ICD and retroviral classification. All the datasets
      involved in this paper and the application software tool of this model can be
      available for free download at
      https://sourceforge.net/projects/icdtool/files/?source=navbar.

PMID- 28454902
TI  - Iron Supplementation, Response in Iron-Deficiency Anemia: Analysis of Five
      Trials.
AB  - BACKGROUND: Oral iron-replacement therapy is the mainstay of treatment for iron
      deficiency anemia, but it is often poorly tolerated or ineffective. Hemoglobin
      response at day 14 of oral iron may be useful in assessing whether and when to
      transition patients from oral to intravenous (IV) iron. METHODS: Pooled data from
      5 randomized trials were analyzed to compare oral and IV iron-replacement therapy
      for iron-deficiency anemia. Treatment criteria and assignment to oral versus IV
      iron were defined per protocol; this analysis included only subjects receiving
      oral iron. Responders were subjects with >=1.0-g/dL increases in hemoglobin at
      day 14, and nonresponders were those with smaller increases. Demographic and
      clinical characteristics were evaluated for association with hemoglobin response
      at multiple timepoints. RESULTS: Most subjects (72.8%) were classified as
      responders. The proportion of subjects with hemoglobin increases >=1.0, >=2.0,
      and >=3.0 g/dL was greatest among those with postpartum anemia, intermediate
      among those with heavy uterine bleeding or gastrointestinal-related causes of
      anemia, and lowest among those with other causes; this proportion was also
      significantly greater among responders than nonresponders. A >=1.0-g/dL increase
      in hemoglobin on day 14 most accurately predicted satisfactory overall hemoglobin
      response to oral iron on day 42/56 (sensitivity 90.1%; specificity 79.3%;
      positive and negative predictive values of 92.9% and 72.7%, respectively). Iron
      replacement therapy improved quality of life and reduced fatigue. CONCLUSION:
      Hemoglobin responses <1.0 g/dL at day 14 of oral iron identify subjects with iron
      deficiency anemia who should be transitioned to IV iron supplementation.

PMID- 28454903
TI  - How Exemplary Inpatient Teaching Physicians Foster Clinical Reasoning.
AB  - BACKGROUND: Clinical reasoning is a crucial component of training in health
      professions. These cognitive skills are necessary to provide quality care and
      avoid diagnostic error. Much previous literature has focused on teaching clinical
      reasoning in nonclinical environments and does not include learner reflections.
      The authors sought to explore, through multiple perspectives including learners,
      techniques used by exemplary inpatient clinician-educators for explicitly
      cultivating clinical reasoning. METHODS: The authors conducted (2014-2015) a
      multisite, exploratory qualitative study examining how excellent clinician
      educators foster clinical reasoning during general medicine rounds. This was
      accomplished through interviews of educators, focus group discussions with
      learners, and direct observations of clinical teaching. The authors reviewed
      field notes and transcripts using techniques of thematic analysis. RESULTS:
      Twelve clinician-educators, 57 current learners, and 26 former learners
      participated in observations and interviews. The techniques and behaviors of
      educators were categorized into 4 themes, including 1) emphasizing organization
      and prioritization, 2) accessing prior knowledge, 3) thinking aloud, and 4)
      analyzing the literature. CONCLUSIONS: The findings of this comprehensive study
      both confirm strategies found in previous literature and provide novel
      approaches. This is the first study to incorporate the perspectives of learners.
      Educators' techniques and behaviors, identified through direct observation and
      supported by reflections from the entire team, can inform best practices for the
      teaching of clinical reasoning.

PMID- 28454904
TI  - Massive Asymptomatic Extrahepatic Portal Vein Aneurysm.

PMID- 28454905
TI  - Why California's Proposition 61 Was a Bad Idea.

PMID- 28454906
TI  - Association Between Patient-Reported Medication Adherence and Anticoagulation
      Control.
AB  - BACKGROUND: The prevention of thromboembolism events remains challenging in cases
      of poor medication adherence. Unfortunately, clinical prediction of future
      adherence has been suboptimal. The objective of this study was to examine the
      correlation between 2 measures of real-time, self-reported adherence and
      anticoagulation control. METHODS: The IN-RANGE2 cohort recruited patients
      initiating warfarin therapy in 3 urban anticoagulation clinics. At each study
      visit, participants reported adherence using a 100-point visual analogue scale
      (VAS, marking percentage of pills taken since prior visit on a linear scale) and
      7-day recall of pill-taking behavior. Anticoagulation control was measured by
      between-visit percent time in international normalized ratio range (BVTR),
      dichotomized at the cohort median. The longitudinal association between adherence
      and anticoagulation control was estimated using generalized estimating equations,
      controlling for clinical and demographic characteristics, prior BVTR, and
      warfarin dose changes. RESULTS: Among 598 participants with 3204 (median 4)
      visits, the median BVTR was 36.8% (interquartile range 0%-73.9%). Participants
      reported <=80% adherence in 182 visits (5.7%) and missed pills in the past 7 days
      in 377 visits (11.8%). Multivariable regression analysis found poorer
      anticoagulation control (BVTR <36.8%) in those with a VAS <=80% (odds ratio 1.89;
      95% confidence interval, 1.12-3.18; P = .02) and self-reported change in
      adherence since last visit (odds ratio 1.55; 95% confidence interval, 1.20-2.01;
      P = .001). CONCLUSION: Self-reported VAS medication adherence at a clinic visit
      and changes in reported adherence since the last visit are independently
      associated with BVTR. Clinicians may gain additional insight into patients'
      medication adherence by incorporating this information into patient management.

PMID- 28454907
TI  - A methodology for developing anisotropic AAA phantoms via additive manufacturing.
AB  - An Abdominal Aortic Aneurysm (AAA) is a permanent focal dilatation of the
      abdominal aorta at least 1.5 times its normal diameter. The criterion of maximum
      diameter is still used in clinical practice, although numerical studies have
      demonstrated the importance of biomechanical factors for rupture risk assessment.
      AAA phantoms could be used for experimental validation of the numerical studies
      and for pre-intervention testing of endovascular grafts. We have applied multi
      material 3D printing technology to manufacture idealized AAA phantoms with
      anisotropic mechanical behavior. Different composites were fabricated and the
      phantom specimens were characterized by biaxial tensile tests while using a
      constitutive model to fit the experimental data. One composite was chosen to
      manufacture the phantom based on having the same mechanical properties as those
      reported in the literature for human AAA tissue; the strain energy and
      anisotropic index were compared to make this choice. The materials for the matrix
      and fibers of the selected composite are, respectively, the digital materials
      FLX9940 and FLX9960 developed by Stratasys. The fiber proportion for the
      composite is equal to 0.15. The differences between the composite behavior and
      the AAA tissue are small, with a small difference in the strain energy (0.4%) and
      a maximum difference of 12.4% in the peak Green strain ratio. This work
      represents a step forward in the application of 3D printing technology for the
      manufacturing of AAA phantoms with anisotropic mechanical behavior.

PMID- 28454908
TI  - Accuracy of mobile biplane X-ray imaging in measuring 6-degree-of-freedom
      patellofemoral kinematics during overground gait.
AB  - The aim of this study was to evaluate the accuracy with which mobile biplane X
      ray imaging can be used to measure patellofemoral kinematics of the intact knee
      during overground gait. A unique mobile X-ray imaging system tracked and recorded
      biplane fluoroscopic images of two human cadaver knees during simulated
      overground walking at a speed of 0.7m/s. Six-degree-of-freedom patellofemoral
      kinematics were calculated using a bone volumetric model-based method and the
      results then compared against those derived from a gold-standard bead-based
      method. RMS errors for patellar anterior translation, superior translation and
      lateral shift were 0.19mm, 0.34mm and 0.37mm, respectively. RMS errors for
      patellar flexion, lateral tilt and lateral rotation were 1.08 degrees , 1.15
      degrees  and 1.46 degrees , respectively. The maximum RMS error for
      patellofemoral translations was approximately one-half that reported previously
      for tibiofemoral translations using the same mobile X-ray imaging system while
      the maximum RMS error for patellofemoral rotations was nearly two times larger
      than corresponding errors reported for tibiofemoral rotations. The lower accuracy
      in measuring patellofemoral rotational motion is likely explained by the
      symmetric nature of the patellar geometry and the smaller size of the patella
      compared to the tibia.

PMID- 28454909
TI  - Asymmetric interlimb role-sharing in mechanical power during human sideways
      locomotion.
AB  - Sideways movement at a wide variety of speeds is required in daily life and
      sports. The purpose of this study was to identify the characteristics of
      asymmetry in power output between lower limbs during sideways gait patterns.
      Seven healthy men performed steady-state sideways locomotion at various speeds.
      The mechanical external power of each limb was calculated and decomposed to the
      lateral and vertical components by the center of mass velocity and ground
      reaction force. We acquired data from 126 steps of sideways walking at 0.44
      1.21m/s, and from 41 steps of sideways galloping at 1.04-3.00m/s. The results
      showed asymmetric power production between the limbs during sideways locomotion.
      During sideways walking, the trailing limb predominantly produced positive
      external power and the leading limb produced predominantly negative external
      power, and these amplitudes increased with step speed. In contrast, during
      sideways galloping, negative and subsequent positive power production was
      observed in both limbs. These differences in asymmetric interlimb role-sharing
      were mainly due to the vertical component. During sideways galloping, the
      trailing limb absorbs vertical power produced by the leading limb due to the
      longer flight time. This characteristic of vertical power production in the
      trailing limb may explain the presence of a double-support phase, which is not
      observed during forward running, even at high speeds. Our results will help to
      elucidate the asymmetric movements of the limbs in lateral directions at various
      speeds.

PMID- 28454910
TI  - Evaluation of an aortic valve prosthesis: Fluid-structure interaction or
      structural simulation?
AB  - Bio-inspired polymeric heart valves (PHVs) are excellent candidates to mimic the
      structural and the fluid dynamic features of the native valve. PHVs can be
      implanted as prosthetic alternative to currently clinically used mechanical and
      biological valves or as potential candidate for a minimally invasive treatment,
      like the transcatheter aortic valve implantation. Nevertheless, PHVs are not
      currently used for clinical applications due to their lack of reliability. In
      order to investigate the main features of this new class of prostheses, pulsatile
      tests in an in-house pulse duplicator were carried out and reproduced in silico
      with both structural Finite-Element (FE) and Fluid-Structure interaction (FSI)
      analyses. Valve kinematics and geometric orifice area (GOA) were evaluated to
      compare the in vitro and the in silico tests. Numerical results showed better
      similarity with experiments for the FSI than for the FE simulations. The maximum
      difference between experimental and FSI GOA at maximum opening time was only 5%,
      as compared to the 46.5% between experimental and structural FE GOA. The stress
      distribution on the valve leaflets clearly reflected the difference in valve
      kinematics. Higher stress values were found in the FSI simulations with respect
      to those obtained in the FE simulation. This study demonstrates that FSI
      simulations are more appropriate than FE simulations to describe the actual
      behaviour of PHVs as they can replicate the valve-fluid interaction while
      providing realistic fluid dynamic results.

PMID- 28454911
TI  - Biomechanical and morphological properties of the multiparous ovine vagina and
      effect of subsequent pregnancy.
AB  - Pelvic floor soft tissues undergo changes during the pregnancy. However, the
      degree and nature of this process is not completely characterized. This study
      investigates the effect of subsequent pregnancy on biomechanical and structural
      properties of ovine vagina. Vaginal wall from virgin, pregnant (in their third
      pregnancy) and parous (one year after third vaginal delivery) Swifter sheep (n=5
      each) was harvested. Samples for biomechanics and histology, were cut in
      longitudinal axis (proximal and distal regions). Outcome measurements describing
      Young's modulus, ultimate stress and elongation were obtained from stress-strain
      curves. For histology samples were stained with Miller's Elastica staining.
      Collagen, elastin and muscle cells and myofibroblasts contents were estimated,
      using image processing techniques. Statistical analyses were performed in order
      to determine significant differences among experimental groups. Significant
      regional differences were identified. The proximal vagina was stiffer than
      distal, irrespective the reproductive status. During the pregnancy proximal
      vagina become more compliant than in parous (+47.45%) or virgin sheep (+64.35%).
      This coincided with lower collagen (-15 to -21%), higher elastin (+30 to +60%),
      and more smooth muscle cells (+17 to +37%). Vaginal tissue from parous ewes was
      weaker than of virgins, coinciding with lower collagen (-10%), higher elastin
      (+50%), more smooth muscle cells (+20%). It could be proposed that after
      pregnancy biomechanical properties of vagina do not recover to those of virgins.
      Since elastin has a significant influence on the compliance of soft tissues and
      collagen is the main "actor" regarding strength, histological analysis performed
      in this study justifies the mechanical behavior observed.

PMID- 28454912
TI  - Phosphonoamidate prodrugs of C5-substituted pyrimidine acyclic nucleosides for
      antiviral therapy.
AB  - Acyclic nucleoside phosphonates (ANPs) are nowadays one of the key drugs in the
      treatment of DNA virus and retrovirus infections. In this work, we report the
      synthesis and antiviral evaluation of phosphonoamidate and diamidates prodrugs of
      C5-pyrimidine acyclic nucleosides derivatives functionalized with but-2-enyl-
      chain. In the phosphonoamidate series, the most active compound 15, showed sub
      micromolar activity against varicella zoster virus (VZV) (EC50 = 0.09-0.5 MUM)
      and MUM activity against human cytomegalovirus (HCMV) and herpes simplex virus
      (HSV). Separation of single diastereoisomers for compound 14, showed that 14b had
      better anti-herpesvirus activity and no cytotoxicity compared to the
      diastereoisomeric mixture 14. Very interestingly, phosphonodiamidate 21 showed
      anti-herpesvirus activity with excellent activity against wild type and thymidine
      kinase-deficient (TK-) VZV strains (EC50 = 0.47 and 0.2 MUM, respectively) and
      HCMV (EC50 = 3.5-7.2 MUM) without any cytotoxicity (CC50 > 100).

PMID- 28454913
TI  - Coinjection of a vaccine and anti-viral agents can provide fast-acting protection
      from foot-and-mouth disease.
AB  - Foot-and-mouth disease (FMD) is the cause of an economically devastating animal
      disease. With commercial inactivated FMD vaccines, the protection against FMD
      virus (FMDV) begins a minimum of 4 days post vaccination (dpv). Therefore,
      antiviral agents could be proposed for rapid protection and to reduce the spread
      of FMDV during outbreaks until vaccine-induced protective immunity occurs. In
      previous studies, we have developed two recombinant adenoviruses that
      simultaneously express porcine interferon-alpha and interferon-gamma (Ad-porcine
      IFN-alphagamma) and multiple siRNAs that target the non-structural protein
      regions of FMDV (Ad-3siRNA), and we have shown that the combination of the two
      antiviral agents (referred to here as Ad combination) induced robust protection
      against FMDV in pigs. In an attempt to provide complete protection against FMDV,
      we co-administered Ad combination and the FMD vaccine to mice and pigs. In the
      C57BL/6 mice model, we observed rapid and continuous protection against
      homologous FMDV challenge from 1 to 3 dpv-the period in which vaccine-mediated
      immunity is absent. In the pig experiments, we found that most of the pigs (five
      out of six) that received vaccine + Ad combination and were challenged with FMDV
      at 1 or 2 dpv were clinically protected from FMDV. In addition, most of the pigs
      that received vaccine + Ad combination and all pigs inoculated with the vaccine
      only were clinically protected from an FMDV challenge at 7 dpv. We believe that
      the antiviral agent ensures early protection from FMDV, and the vaccine
      participates in protection after 7 dpv. Therefore, we can say that the
      combination of the FMD vaccine and effective antiviral agents may offer both fast
      acting and continuous protection against FMDV. In further studies, we plan to
      design coadministration of Ad combination and novel vaccines.

PMID- 28454915
TI  - Brain microglia in psychiatric disorders.
AB  - The role of immune activation in psychiatric disorders has attracted considerable
      attention over the past two decades, contributing to the rise of a new era for
      psychiatry. Microglia, the macrophages of the brain, are progressively becoming
      the main focus of the research in this field. In this Review, we assess the
      literature on microglia activation across different psychiatric disorders,
      including post-mortem and in-vivo studies in humans and experimental studies in
      animals. Although microglia activation has been noted in all types of psychiatric
      disorder, no association was seen with specific diagnostic categories.
      Furthermore, the findings from these studies highlight that not all psychiatric
      patients have microglial activation. Therefore, the cause of the
      neuroinflammation in these cohorts and its implications are unclear. We discuss
      psychosocial stress as one of the main factors determining microglial activation
      in patients with psychiatric disorders, and explore the relevance of these
      findings for future treatment strategies.

PMID- 28454914
TI  - Genetic and epigenetic regulation of arrhythmogenic cardiomyopathy.
AB  - Arrhythmogenic cardiomyopathy (AC) is most commonly characterized as a disease of
      the intercalated disc that promotes abnormal cardiac conduction. Previously,
      arrhythmogenic cardiomyopathy was frequently referred to as arrhythmogenic right
      ventricular cardiomyopathy/dysplasia (ARVC/D); however, genotype-phenotype
      studies have defined a broader phenotypic spectrum; with the identification of
      left-dominant and biventricular subtypes. Molecular insight into AC has primarily
      focused on mutations in desmosomal proteins and the downstream signaling
      pathways; however, desmosomal gene mutations can only be identified in
      approximately 50% of patients with AC. Animal and cellular studies have shown
      that in addition to abnormal biomechanical properties from changes in desmosome
      function, crosstalk from the desmosome to the nucleus, gap junctions, and ion
      channels are implicated in the pathobiology of AC. In this review, we highlight
      some of the newly identified genetic and epigenetic mechanisms that may lead to
      the development of AC including the role of the Hippo pathway and microRNAs. This
      article is part of a Special Issue entitled: Genetic and epigenetic control of
      heart failure - edited by Jun Ren & Megan Yingmei Zhang.

PMID- 28454916
TI  - Behavioral laterality in Yangtze finless porpoises (Neophocaena asiaeorientalis
      asiaeorientalis).
AB  - The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) is a
      critically endangered species with less than 1000 individuals expected to be left
      in the wild. While many studies have been conducted on laterality among several
      cetacean species, no studies investigating the Yangtze finless porpoise have been
      conducted. Using event sampling methods, several behaviors such as flipper-body
      touching, object touching, barrel-rolls, side swimming, and swimming direction
      were recorded from six captive porpoises (three males and three females).
      Analyses of 360 observations recorded over two months revealed that, at group
      level, porpoises showed laterality in swimming behaviors. Porpoises swam
      preferentially with their right pectoral fin upward and their left pectoral fin
      downward with a clockwise swimming direction and also displayed a consistent bias
      for a counterclockwise barrel-roll direction. No significant differences were
      reported for flipper use either during the interaction with conspecifics or with
      objects. The results from the current study provide novel insight into the
      cerebral asymmetry in a species previously ignored within the literature, thus
      improving our understanding on the extent of laterality in cetaceans and on the
      evolutionary history of hemispheric laterality for vertebrates in general.

PMID- 28454917
TI  - To be so bold: boldness is repeatable and related to within individual
      behavioural variability in North Island robins.
AB  - Behavioural research traditionally focusses on the mean responses of a group of
      individuals rather than variation in behaviour around the mean or among
      individuals. However, examining the variation in behaviour among and within
      individuals may also yield important insights into the evolution and maintenance
      of behaviour. Repeatability is the most commonly used measure of variability
      among individuals in behavioural research. However, there are other forms of
      variation within populations that have received less attention. One such measure
      is intraindividual variation in behaviour (IIV), which is a short-term
      fluctuation of within-individual behaviour. Such variation in behaviour might be
      important during interactions because it could decrease the ability of
      conspecific and heterospecific individuals to predict the behaviour of the
      subject, thus increasing the cost of the interaction. In this experiment, we made
      repeated measures of the latency of North Island robins to attack a prey in a
      novel situation (a form of boldness) and examined (i) repeatability of boldness
      (the propensity to take a risk), (ii) IIV of boldness, and (iii) whether there
      was a significant relationship between these two traits (a behavioural syndrome).
      We found that boldness was highly repeatable, that there were high levels of IIV
      in boldness, and that there was a negative relationship between boldness and IIV
      in boldness. This suggests that despite high levels of repeatability for this
      behaviour, there were also still significant differences in IIV among different
      individuals within the population. Moreover, bolder individuals had significantly
      less IIV in their boldness, which suggests that they were forming routines (which
      reduces behavioural variability) compared to shyer individuals. Our results
      definitively demonstrate that IIV itself varies across individuals and is linked
      with key behavioural traits, and we argue for the importance of future studies
      aimed at understanding its causes and consequences for behavioural interactions.

PMID- 28454918
TI  - Targeting Leishmania amazonensis amastigotes through macrophage internalisation
      of a hydroxymethylnitrofurazone nanostructured polymeric system.
AB  - Dextran-coated poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NPs) were
      prepared and were evaluated for enhanced delivery of a promising anti-Leishmania
      drug candidate, hydroxymethylnitrofurazone (NFOH), to phagocytic cells. Currently
      available chemotherapy for leishmaniasis, such as pentavalent antimonials,
      presents low safety and efficacy. Furthermore, widespread drug resistance in
      leishmaniasis is rapidly emerging. To overcome these drawbacks, the use of
      nanosized delivery systems can reduce systemic drug toxicity and increase the
      drug concentration in infected macrophages, therefore improving treatment of
      leishmaniasis. PBCA-NPs containing NFOH (PBCA-NFOH-NPs) were prepared by an
      anionic emulsion polymerisation method. The z-average and polydispersity index
      (PDI) were determined by photon correlation spectroscopy, the zeta potential by
      microelectrophoresis and the entrapment efficiency by HPLC. Cytotoxicity was
      determined using macrophages from BALB/c mice. Efficacy tests were performed
      using Leishmania amazonensis promastigotes and amastigotes. The z-average of PBCA
      NFOH-NPs was 151.5 +/- 61.97 nm, with a PDI of 0.104 +/- 0.01, a zeta potential
      of -10.1 +/- 6.49 mV and an entrapment efficiency of 64.47 +/- 0.43%. Efficacy in
      amastigotes revealed IC50 values of 0.33 uM and 31.2 uM for the nanostructured
      and free NFOH, respectively (95-fold increase). The cytotoxicity study indicated
      low toxicity of the PBCA-NFOH-NPs to macrophages. The selectivity index was
      370.6, which is 49-fold higher than free NFOH (7.6). Such findings indicated that
      improved efficacy could be due to NP internalisation following site-specific drug
      delivery and reactivation of immune protective reactions by the NP components.
      Thus, PBCA-NFOH-NPs have the potential to significantly improve the treatment of
      leishmaniasis, with reduced systemic side effects.

PMID- 28454919
TI  - New amino acid-Schiff base derived from s-allyl cysteine and methionine
      alleviates carbon tetrachloride-induced liver dysfunction.
AB  - In spite of the tremendous stride in modern medicine, conventional drugs used in
      the hepatotoxic management are mostly inadequate. The present study aims in the
      synthesis of novel Schiff base compound derived using s-allyl cystiene and
      methionine. The newly synthesized compound, 2-((2-((2-(allylthio)-1
      carboxyethyl)imino)ethylidene)amino)-4-(methylthio)butanoic acid (ACEMB) was
      characterized using UV-visible spectrophotometer, FTIR, 1HNMR, and GC-MS. ACEMB
      showed potent in vitro antioxidant property. Chronic administration of ACEMB
      prior to CCl4 intoxication: i) attenuated the leakage of liver injury markers,
      such as, enzymes (AST, ALT, GGT, ALP and LDH) and biomolecules (bilirubin) into
      the blood circulation; ii) normalized the concentration of total proteins,
      albumin and globulin to control level; and iii) protected the liver against
      dyslipidemia. These effects of ACEMB show the preservation of endoplasmic
      reticulum function against CCl4 toxicity in the liver. The protective effect of
      ACEMB was due to its antioxidant property, which was revealed by reduced
      oxidative stress (TBARS and HP) and enhanced functions of the endogenous
      antioxidative system (SOD, catalase, GPx, GST, GSH, vitamin E and C) against CCl4
      intoxication. Also, ACEMB protected the functional activities of the various
      mitochondrial tricarboxylic acid cycle and oxidative phosphorylation enzymes. The
      biochemical alterations are in concurrence with the histological observations,
      wherein ACEMB pretreatment prevented the vacuolation, degeneration of nuclei and
      necrosis of hepatocytes. In addition, in silico analysis reveals the interaction
      of ACEMB in the active site of cytochrome P450. ACEMB mediates hepatoprotective
      effect by substituting itself as an antioxidant and decreasing oxidative stress,
      thereby diminishing the intracellular organelle dysfunction against CCl4 toxicity
      in the liver.

PMID- 28454920
TI  - Automated analysis of written narratives reveals abnormalities in referential
      cohesion in youth at ultra high risk for psychosis.
AB  - Schizophrenia and at-risk populations are suggested to exhibit referential
      cohesion deficits in language production (e.g., producing fewer pronouns or nouns
      that clearly link to concepts from previous sentences). Much of this work has
      focused on transcribed speech samples, while no work to our knowledge has
      examined referential cohesion in written narratives among ultra high risk (UHR)
      youth using Coh-Metrix, an automated analysis tool. In the present study, written
      narratives from 84 individuals (UHR=41, control=43) were examined. Referential
      cohesion variables and relationships with symptoms and relevant cognitive
      variables were also investigated. Findings reveal less word "stem" overlap in
      narratives produced by UHR youth compared to controls, and correlations with
      symptom domains and verbal learning. The present study highlights the potential
      usefulness of automated analysis of written narratives in identifying at-risk
      youth and these data provide critical information in better understanding the
      etiology of psychosis. As writing production is commonly elicited in educational
      contexts, markers of aberrant cohesion in writing represent significant potential
      for identifying youth who could benefit from further screening, and utilizing
      software that is easily accessible and free may provide utility in academic and
      clinical settings.

PMID- 28454921
TI  - Interpersonal sensitivity in those at clinical high risk for psychosis mediates
      the association between childhood bullying victimisation and paranoid ideation: A
      virtual reality study.
AB  - BACKGROUND: Experience of bullying victimisation in childhood and heightened
      interpersonal sensitivity have been independently linked to the clinical high
      risk for psychosis. AIM: To examine the potential mediating effect of
      interpersonal sensitivity in explaining the link between childhood bullying
      victimisation and real-time paranoid ideation in adult participants at clinical
      high risk for psychosis. METHOD: In a cross-sectional study data were collected
      for 64 individuals at clinical high risk for psychosis. Measures included history
      of bullying victimisation, interpersonal sensitivity and state paranoid ideation
      following exposure to a social virtual reality environment. The virtual reality
      scenario was a London Underground journey. RESULTS: Path analysis indicated that
      interpersonal sensitivity fully explained the significant association between
      severe bullying victimisation in childhood and paranoid ideation in the clinical
      high risk group. Based on AIC criteria the best model selected was the full
      mediation model: severe bullying->interpersonal sensitivity->state paranoid
      ideation. The results suggest that severity of bullying is more important than
      frequency of bullying in explaining state paranoid ideation. CONCLUSIONS: The
      significant role played by interpersonal sensitivity in the association between
      being bullied in childhood and paranoid ideation in the clinical high risk group
      suggests that this could become a target for intervention.

PMID- 28454922
TI  - Paliperidone palmitate once-monthly maintains improvement in functioning domains
      of the Personal and Social Performance scale compared with placebo in subjects
      with schizoaffective disorder.
AB  - OBJECTIVE: Evaluate the effect of paliperidone palmitate once-monthly (PP1M)
      injectable on the specific functioning domains of the Personal and Social
      Performance (PSP) scale in patients with schizoaffective disorder (SCA)
      participating in a long-term study. METHODS: This study (NCT01193153) included
      both in- and outpatient subjects with SCA experiencing an acute exacerbation of
      psychotic and mood symptoms. Subjects were treated with PP1M either as
      monotherapy or in combination with antidepressants or mood stabilizers during a
      25-week open-label (OL) phase. Stabilized subjects were randomly assigned 1:1
      (PP1M or placebo) into a 15-month double-blind (DB) relapse-prevention period.
      Functioning of the randomized subjects during OL and DB phases was evaluated
      using the PSP scale (four domains: socially useful activities, personal/social
      relationships, self-care, and disturbing/aggressive behaviors). Three statistical
      approaches were utilized to analyze PSP scores to assess robustness and
      consistency of findings. No adjustments were made for multiplicity. RESULTS: 334
      of 667 enrolled subjects were stabilized with PP1M, randomly assigned to PP1M
      (n=164) or placebo (n=170) in the DB phase, and included in this analysis.
      Improvements in all PSP domain scores were observed during the OL phase and were
      maintained during the DB phase with PP1M, but decreased with placebo. Differences
      compared to placebo were significant in all four PSP domains during the DB phase
      (P<=0.008). CONCLUSION: The analysis in this study showed that PP1M improves
      functioning, as measured by the four PSP domain scores, in symptomatic subjects
      with SCA. Functioning was maintained compared with placebo.

PMID- 28454923
TI  - Prevalence and predictors of metabolic syndrome in patients with schizophrenia
      and healthy controls: A study in rural South Indian population.
AB  - INTRODUCTION: Metabolic syndrome (MetS) has been extensively studied as a co
      morbidity in patients with schizophrenia. A disparity is noted between hospital
      and community based estimates in India. We aimed to examine the prevalence and
      predictors of MetS in schizophrenia patients and general population controls in a
      rural population in South India. METHODS: Patients (n=157) and general population
      controls (n=263) were recruited from a rural area in South India. Diagnosis of
      MetS was established using International Diabetes Federation (IDF) criteria.
      Patients were also assessed on clinical parameters, treatment details, dietary
      and physical activity patterns. Predictors of MetS were estimated based on
      subgrouping of patients with and without MetS. RESULTS: 50 (31.8%) of the
      patients and 76 (28.9%) of the controls were diagnosed to have MetS. Female
      gender and ongoing antipsychotic exposure were noted to be significant predictors
      of MetS with odds ratio (95% confidence interval) of 2.87 (1.2-6.86) and 4.42
      (1.37-14.25) respectively. Three empirically defined treatment groups 'never
      treated', 'ever treated' and 'continuous treatment' groups had odds ratios (95%
      CI) of 0.53 (1.68-6.58), 0.92 (0.5-1.69) and 3.33 (1.68-6.58) when compared to
      the control group. CONCLUSIONS: Patients who were naive to antipsychotics had a
      significantly lower prevalence of MetS compared to general population. This
      finding doesn't support the antipsychotic independent risk for MetS in patients
      with schizophrenia. Female gender and regular antipsychotic exposure predicted
      MetS.

PMID- 28454924
TI  - Dual effect of silymarin on experimental non-alcoholic steatohepatitis induced by
      irinotecan.
AB  - Irinotecan-based regimens are commonly used for treatment of colorectal cancer,
      which is limited by mucositis and non-alcoholic steatohepatitis (NASH). Silymarin
      (SIL) prevents fatty liver disease in the clinical setting and in models of liver
      damage induced chemically. This study investigated the possible effect of SIL on
      irinotecan (IRI)-induced NASH. Swiss female mice were injected with saline (SAL
      5ml/kg i.p.), IRI (50mg/kg i.p.), SIL (150mg/kg p.o.) or IRI (50mg/kg i.p.)+(SIL
      1.5, 15 or 150mg/kg p.o.) thrice/week/7weeks. On the seventh week, blood samples
      were collected for transaminases assay and livers were collected for
      histopathology, measurement of the total lipids, malondyadehyde (MDA), non
      protein sulfhydryl groups (NPSH), cytokines (IL-1beta, IL 6 and IL-10), 3
      nitrotyrosine (N-Tyr) and toll-like receptor 4 (TLR4) immunoexpression,
      quantification of NF-kB, alpha-smooth muscle actin (alpha-SMA), and Escherichia
      coli 16S rRNA gene (RRS) expression. IRI increased liver transaminases,
      neutrophil infiltration, lipid accumulation, MDA, IL-1beta and IL-6 levels, N-Tyr
      and TLR4 immunostaining, NF-kB, alpha-SMA expression and RRS versus the SAL group
      (p<0.05). Additionally, SIL (1.5mg/kg) improved these parameters (p<0.05), except
      neutrophil infiltration and RSS versus the IRI group. Furthermore, the SIL
      (15mg/kg) only improved the inflammatory parameters, the expression of alpha-SMA
      and RRS versus the IRI group (p<0.05). The higher dose of SIL (150mg/kg) was even
      more deleterious than the intermediate dose. Therefore, silymarin showed a dual
      effect on liver damage induced by IRI. Hepatoprotection seems to involve the
      inhibition of oxidative stress and protein nitrosylation, preventing activation
      of hepatic fibrosis mechanisms.

PMID- 28454925
TI  - Cross-tolerance effects due to adult heat hardening, desiccation and starvation
      acclimation of tropical drosophilid-Zaprionus indianus.
AB  - Some insect taxa from polar or temperate habitats have shown cross-tolerance for
      multiple stressors but tropical insect taxa have received less attention.
      Accordingly, we considered adult flies of a tropical drosophilid-Zaprionus
      indianus for testing direct as well as cross-tolerance effects of rapid heat
      hardening (HH), desiccation acclimation (DA) and starvation acclimation (SA)
      after rearing under warmer and drier season specific simulated conditions. We
      observed significant direct acclimation effects of HH, DA and SA; and four cases
      of cross-tolerance effects but no cross-tolerance between desiccation and
      starvation. Cross-tolerance due to heat hardening on desiccation showed 20%
      higher effect than its reciprocal effect. There is greater reduction of water
      loss in heat hardened flies (due to increase in amount of cuticular lipids) as
      compared with desiccation acclimated flies. However, cross-tolerance effect of SA
      on heat knockdown was two times higher than its reciprocal. Heat hardened and
      desiccation acclimated adult flies showed substantial increase in the level of
      trehalose and proline while body lipids increased due to heat hardening or
      starvation acclimation. However, maximum increase in energy metabolites was
      stressor specific i.e. trehalose due to DA; proline due to HH and total body
      lipids due to SA. Rapid changes in energy metabolites due to heat hardening seem
      compensatory for possible depletion of trehalose and proline due to desiccation
      stress; and body lipids due to starvation stress. Thus, observed cross-tolerance
      effects in Z. indianus represent physiological changes to cope with multiple
      stressors related to warmer and drier subtropical habitats.

PMID- 28454926
TI  - Predictive Factors for Nonsentinel Lymph Node Metastasis in Patients With
      Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy: Nomogram for
      Predicting Nonsentinel Lymph Node Metastasis.
AB  - INTRODUCTION: Axillary lymph node (ALN) status is an important prognostic factor
      for breast cancer patients. With increasing numbers of patients undergoing
      neoadjuvant chemotherapy (NAC), issues concerning sentinel lymph node biopsy
      (SLNB) after NAC have emerged. PATIENTS AND METHODS: We analyzed the
      clinicopathologic features and developed a nomogram to predict the possibility of
      nonsentinel lymph node (NSLN) metastases in patients with positive SLNs after
      NAC. A retrospective medical record review was performed of 140 patients who had
      had clinically positive ALNs at presentation, had a positive SLN after NAC on
      subsequent SLNB, and undergone axillary lymph node dissection (ALND) from 2008 to
      2014. RESULTS: On multivariate stepwise logistic regression analysis, pathologic
      T stage, lymphovascular invasion, SLN metastasis size, and number of positive SLN
      metastases were independent predictors for NSLN metastases (P < .05). The NAC
      nomogram was based on these 4 variables. A receiver operating characteristic
      curve was plotted, and the area under the curve (AUC) was 0.791 for the NAC
      nomogram. In the internal validation of performance, the AUCs for the training
      and test sets were 0.801 and 0.760, respectively. The nomogram was validated in
      an external patient cohort, with an AUC of 0.705. CONCLUSION: The Samsung Medical
      Center NAC nomogram was developed to predict the likelihood of additional
      positive NSLNs. The Samsung Medical Center NAC nomogram could provide information
      to surgeons regarding whether to perform additional ALND when the permanent
      biopsy revealed positive findings, although the intraoperative SLNB findings were
      negative.

PMID- 28454927
TI  - Antifungal activity of essential oils extract from Origanum floribundum Munby,
      Rosmarinus officinalis L. and Thymus ciliatus Desf. against Candida albicans
      isolated from bovine clinical mastitis.
AB  - OBJECTIVE: The aim of this study is to limit the antibiotic use in mastitis
      treatment and to find other alternatives. The antifungal activity of the
      essential oils from Origanum floribundum Munby., Rosmarinus officinalis L. and
      Thymus ciliatus Desf. is studied in the present work against a Candida albicans
      reference strain and ten C. albicans isolated strains from bovine clinical
      mastitis. MATERIALS AND METHODS: Essential oils were extracted by
      hydrodistillation technique using Clevenger apparatus. Their chromatographic
      analysis was performed with a Gas Chromatograph/Mass Spectrometer (GC/MS).
      Antifungal activities of essential oils were investigated by macrobroth method of
      dilution in tubes to determine the Minimum Inhibitory Concentrations (MIC 80%).
      RESULTS: Analysis of the essential oil showed chemical profile dominated by
      thymol (50.47 and 62.41%) and P-cymene (24.22 and 15.51%) in the oregano and the
      thyme respectively, 1, 8-cineol (31.50%) and alpha-pinene (18.33%) in Rosemary.
      The three essential oils revealed highly effective anticandidal activity, with an
      MIC of 80% values ranged from 15.02 to 31.08MUg/mL. CONCLUSION: These results
      suggest that essential oils studied can be real alternatives in the control of
      mastitis fungi but deserving studies more in-depth and detailed on their
      application in vivo.

PMID- 28454928
TI  - Community-Partnered Research With Urban School Districts That Serve Children With
      Autism Spectrum Disorder.
AB  - OBJECTIVE: To illustrate the process of community-partnered participatory
      research to develop and evaluate interventions for children with autism in urban
      school districts. METHODS: We formed partnerships of school personnel, parents,
      and researchers to guide the project. We then conducted focus groups, key
      informant interviews, and town halls to explore how public schools currently
      serve students with autism. We used findings from these activities to adapt
      interventions for public schools. We then tested interventions in randomized
      clinical trials (RCTs). RESULTS: Community input indicated a particular need for
      interventions to improve children's social interaction and instructional supports
      to promote their success throughout the day. On the basis of this input, we
      adapted 2 interventions: Remaking Recess for improving peer engagement during
      social times; and Schedules, Tools, and Activities for Transition (STAT) for
      facilitating successful transitions between activities throughout the daily
      routine. Results of the RCT of Remaking Recess are not yet available. The RCT of
      STAT involved 150 children and 56 teachers. Teachers reported high buy-in and
      increased their proficiency at implementing STAT; children with ASD reduced their
      disruptive behavior and made progress toward teacher-nominated goals. However,
      teachers' implementation remained inconsistent, and children did not reliably
      improve in academic engagement or independence. CONCLUSIONS: The findings suggest
      that although community-partnered participatory research has limitations, it can
      assist in selecting interventions to address community priorities and produce
      some favorable outcomes for children with autism in public schools. An important
      next step is to evaluate the sustainability of the interventions introduced in
      this project.

PMID- 28454929
TI  - Real-World Usage of Educational Media Does Not Promote Parent-Child Cognitive
      Stimulation Activities.
AB  - OBJECTIVE: To determine whether educational media as actually used by low-income
      families promote parent-child cognitive stimulation activities. METHODS: We
      performed secondary analysis of the control group of a longitudinal cohort of
      mother-infant dyads enrolled postpartum in an urban public hospital. Educational
      media exposure (via a 24-hour recall diary) and parent-child activities that may
      promote cognitive stimulation in the home (using StimQ) were assessed at 6, 14,
      24, and 36 months. RESULTS: Data from 149 mother-child dyads, 93.3% Latino, were
      analyzed. Mean (standard deviation) educational media exposure at 6, 14, 24, and
      36 months was, respectively, 25 (40), 42 (58), 39 (49), and 39 (50) minutes per
      day. In multilevel model analyses, prior educational media exposure had small
      positive relationship with subsequent total StimQ scores (beta = 0.11, P = .03)
      but was nonsignificant (beta = 0.08, P = .09) after adjusting for confounders
      (child: age, gender, birth order, noneducational media exposure, language;
      mother: age, ethnicity, marital status, country of origin, language, depressive
      symptoms). Educational media did predict small increases in verbal interactions
      and toy provision (adjusted models, respectively: beta = 0.13, P = .02; beta =
      0.11; P = .03). In contrast, more consistent relationships were seen for models
      of the relationship between prior StimQ (total, verbal interactions and teaching;
      adjusted models, respectively: beta = 0.20, P = .002; beta = 0.15, P = .006; beta
      = 0.20, P = .001) and predicted subsequent educational media. CONCLUSIONS:
      Educational media as used by this sample of low-income families does not promote
      cognitive stimulation activities important for early child development or
      activities such as reading and teaching.

PMID- 28454930
TI  - Integrative inference of population history in the Ibero-Maghrebian endemic
      Pleurodeles waltl (Salamandridae).
AB  - Inference of population histories from the molecular signatures of past
      demographic processes is challenging, but recent methodological advances in
      species distribution models and their integration in time-calibrated
      phylogeographic studies allow detailed reconstruction of complex biogeographic
      scenarios. We apply an integrative approach to infer the evolutionary history of
      the Iberian ribbed newt (Pleurodeles waltl), an Ibero-Maghrebian endemic with
      populations north and south of the Strait of Gibraltar. We analyzed an extensive
      multilocus dataset (mitochondrial and nuclear DNA sequences and ten polymorphic
      microsatellite loci) and found a deep east-west phylogeographic break in Iberian
      populations dating back to the Plio-Pleistocene. This break is inferred to result
      from vicariance associated with the formation of the Guadalquivir river basin. In
      contrast with previous studies, North African populations showed exclusive mtDNA
      haplotypes, and formed a monophyletic clade within the Eastern Iberian lineage in
      the mtDNA genealogy. On the other hand, microsatellites failed to recover
      Moroccan populations as a differentiated genetic cluster. This is interpreted to
      result from post-divergence gene flow based on the results of IMA2 and Migrate
      analyses. Thus, Moroccan populations would have originated after overseas
      dispersal from the Iberian Peninsula in the Pleistocene, with subsequent gene
      flow in more recent times, implying at least two trans-marine dispersal events.
      We modeled the distribution of the species and of each lineage, and projected
      these models back in time to infer climatically favourable areas during the mid
      Holocene, the last glacial maximum (LGM) and the last interglacial (LIG), to
      reconstruct more recent population dynamics. We found minor differences in
      climatic favourability across lineages, suggesting intraspecific niche
      conservatism. Genetic diversity was significantly correlated with the
      intersection of environmental favourability in the LIG and LGM, indicating that
      populations of P. waltl are genetically more diverse in regions that have
      remained environmentally favourable through the last glacial cycle, particularly
      southern Iberia and northern Morocco. This study provides novel insights into the
      relative roles of geology and climate on the biogeography of a biodiversity
      hotspot.

PMID- 28454931
TI  - Neuroprotective effect of minocycline on cognitive impairments induced by
      transient cerebral ischemia/reperfusion through its anti-inflammatory and anti
      oxidant properties in male rat.
AB  - Memory deficit is the most visible symptom of cerebral ischemia that is
      associated with loss of pyramidal cells in CA1 region of the hippocampus.
      Oxidative stress and inflammation may be involved in the pathogenesis of
      ischemia/reperfusion (I/R) damage. Minocycline, a semi-synthetic tetracycline
      derived antibiotic, has anti-inflammatory and antioxidant properties. We
      evaluated the neuroprotective effect of minocycline on memory deficit induced by
      cerebral I/R in rat. I/R was induced by occlusion of common carotid arteries for
      20min. Minocycline (40mg/kg, i.p.) was administered once daily for 7days after
      I/R. Learning and memory were assessed using the Morris water maze test. Nissl
      staining was used to evaluate the viability of CA1 pyramidal cells. The effects
      of minocycline on the microglial activation was also investigated by Iba1
      (Ionized calcium binding adapter molecule 1) immunostaining. The content of
      malondialdehyde (MDA) and pro-inflammatory cytokines (IL-1beta and TNF-alpha) in
      the hippocampus were measured by thiobarbituric acid reaction substances method
      and ELISA, respectively. Minocycline reduced the increase in escape latency time
      and in swimming path length induced by cerebral I/R. Furthermore, the ischemia
      induced reduction in time spent in the target quadrant during the probe trial was
      increased by treatment with minocycline. Histopathological results indicated that
      minocycline prevented pyramidal cells death and microglial activation induced by
      I/R. Minocycline also reduced the levels of MDA and pro-inflammatory cytokines in
      the hippocampus in rats subjected to I/R. Minocycline has neuroprotective effects
      on memory deficit induced by cerebral I/R in rat, probably via its anti
      inflammatory and antioxidant properties.

PMID- 28454932
TI  - Single-cannula, single-incision thoracoscopic anatomic segmentectomy after
      pneumonectomy.

PMID- 28454933
TI  - Is it time for some new ideas for patients undergoing the Fontan operation? Here
      is some food for thought.

PMID- 28454934
TI  - Changes in the hop-derived volatile profile upon lab scale boiling.
AB  - Hop terpenes might be oxidized during kettle boiling into more water soluble
      compounds that could contribute to 'hoppy' aroma of kettle hopped lager beers.
      Our current research proves that the boiling process induces significant changes
      in the hop oil volatile profile. The discrimination between volatile profiles of
      unboiled and boiled hop essential oil was evaluated via principal component and
      cluster analysis (PCA and CA). HS-SPME-GC-MS analysis revealed quantitative
      changes (e.g. increases in the levels of oxygenated alpha-humulene and beta
      caryophyllene derivatives) as well as qualitative changes (i.e. detection of
      compounds, not found in unboiled hop essential oil) in the hop oil volatile
      profile upon boiling. Many of these compounds were previously found in lager beer
      and may therefore contribute to beer flavor. Interestingly, the analytical
      difference between unboiled and boiled hop essential oil proved to be more
      pronounced as the initial hop essential oil concentration used for boiling was
      increased. In addition, lager beers spiked with boiled hop oil were described as
      'hoppy/spicy' during sensory evaluations. Therefore, the newly formed products
      and hop oil constituents that are characterized by an increased recovery after
      boiling, are candidate compounds for 'hoppy' aroma in real brewing practice.

PMID- 28454935
TI  - NMR fingerprinting as a tool to evaluate post-harvest time-related changes of
      peaches, tomatoes and plums.
AB  - The time-related changes of three agricultural products, coming from two
      distribution routes, have been followed using NMR fingerprinting to monitor
      metabolic variations occurring during several days of cold storage. An NMR
      profiling approach was employed to evaluate the variations in metabolic profile
      and metabolite content in three different agricultural products highly consumed
      in Italy (peaches, tomatoes and plums) coming from Tuscanian farms and how they
      change with time after collection. For each product, we followed the time-related
      changes during cold storage along three different collection periods. We
      monitored the variations in metabolic fingerprint and the trend of a set of
      metabolites, focusing our attention on nutritive and health-promoting metabolites
      (mainly, essential amino acids and antioxidants) as well as metabolites that
      contribute to the taste. Concurrently, for comparison, the time-dependent changes
      of the same kind of products coming from large-scale distribution have been also
      analyzed under the same conditions. In this second category, only slight
      variations in the metabolic fingerprint and metabolite levels were seen during
      cold storage. Unsupervised and supervised multivariate statistics was also
      employed to enlighten the differences between the three collections. In
      particular it seems that the metabolic fingerprint of large-scale distribution
      products is quite similar in the early, middle and late collection, while peaches
      and plums locally collected are markedly different among the three periods. The
      metabolic profiles of the agricultural products belonging to these two different
      distribution routes are intrinsically different, and they show different changes
      during the time of cold storage.

PMID- 28454936
TI  - Modelling the effect of pH, sodium chloride and sodium pyrophosphate on the
      thermal resistance of Escherichia coli 0157:H7 in ground beef.

PMID- 28454937
TI  - Development of an ultrasonic shear reflection technique to monitor the
      crystallization of cocoa butter.
AB  - The quasi-isothermal crystallization process of cocoa butter was monitored by an
      ultrasonic shear reflection technique utilizing a custom-built experimental set
      up in a temperature controlled environment. To facilitate the interpretation of
      the measurement results, the propagation of shear waves was first theoretically
      studied in different configurations of gas, liquid or solid layers with varying
      thickness for the case of normal incidence, yielding theoretical equations of the
      shear wave reflection coefficient (swRC) for different layering conditions. The
      typical experimentally observed pattern of the swRC during quasi-isothermal cocoa
      butter crystallization was subsequently linked to the theoretical equations. The
      remarkable oscillatory damped response in the swRC as function of the
      crystallization time could be explained by constructive and destructive
      interference of a first reflection at the boundary between a plexiglass delay
      line and the crystallized cocoa butter and a second reflection occurring at the
      interface between crystallized and liquid substance. This hypothesis was
      supported by the excitation frequency dependence of the oscillations. The quality
      of the fit of the theoretical model to the experimental results was very good and
      also the reproducibility between different independent measurements was
      acceptable. Finally, measurements at different temperatures (18 degrees C and 20
      degrees C) suggested that the technique was able to detect differences in
      crystallization behavior, as measurements at 18 degrees C displayed faster
      oscillations compared to measurements at 20 degrees C. Moreover, this was also
      confirmed by the theoretical model, as a higher value of the crystallization rate
      parameter K, exhibited more rapid oscillations.

PMID- 28454938
TI  - Cell Wall Disruption of Rape Bee Pollen Treated with Combination of Protamex
      Hydrolysis and Ultrasonication.
AB  - Bee pollen possesses a broad range of potential biological activities, but
      nutrient absorption and biological activities of bee pollen may be restricted due
      to complex pollen wall. This study aimed to investigate wall-disruption
      variations of Brassica campestris L. (rape) bee pollen treated with protamex
      hydrolysis, ultrasonication, and combination of protamex hydrolysis and
      ultrasonication. Pollen sample treated with these three treatments had higher
      specific surface area values and smaller particle sizes than the untreated
      sample. Protamex hydrolysis degraded the pollen coat and disintegrated the intine
      at the germinal apertures. Ultrasonication treatment cracked the pollen exine
      into fragments, but seemed to have little effect on the intine. The combination
      of protamex hydrolysis and ultrasonication can degrade pollen coat and entirely
      disrupt both the exine and the intine. The exine of rape bee pollen was disrupted
      into three fragments along germinal apertures.

PMID- 28454939
TI  - The effects of food advertising on food-related behaviours and perceptions in
      adults: A review.
AB  - The purpose of this research is to gain an understanding of how exposure to food
      advertising affects food related behaviours and perceptions in adults. This
      review assessed other reviews, commentaries as well as experimental studies. The
      results varied; however, the majority of the literature reported a significant
      positive association between food advertising and food choices. Additional
      significant findings include: gender differences in regard to the tendency to
      become immersed in what one is viewing and how that impacts food choice; the role
      of image type on taste perception; and the influence of healthy food advertising
      on consumer behaviour. The goal of this research is to increase public awareness
      in regard to the behavioural and perceptual impacts of food advertising, and to
      inform and influence the decisions of health professionals and policy makers.

PMID- 28454940
TI  - Dynamics of moisture diffusivity in solid triacylglycerol matrices.
AB  - The effects of lipid formulation in combination with two crystallization
      conditions, shearing and non-shearing, on the mechanism of water diffusivity were
      investigated. Five formulations of lipid which varied in fatty acid compositions,
      solid fat particles, and emulsifier levels were assessed at 5, 20, and 30 degrees
      C. Polarized light microscopy was used to study microstructural properties of the
      samples under dynamic and static conditions; and their moisture permeability was
      examined using gravimetric technique (ASTM E-96). All formulations and
      crystallization techniques were confirmed to have a large impact on the
      crystallization properties and dynamics of moisture migration. Dynamic
      crystallized samples showed altered structures with different patterns of
      crystalline clusters. Different values of water diffusivity suggested that
      shearing affected moisture diffusivity of the samples differently. This effect of
      shearing was more pronounced in the presence of lecithin. A higher migration rate
      was observed in sheared samples that contained higher amount of long chain
      saturated fatty acids.

PMID- 28454941
TI  - Ultrasound treatments improve the microbiological quality of water reservoirs
      used for the irrigation of fresh produce.
AB  - Irrigation water has been highlighted as a source of microbial contamination in
      produce. Water treatment has been recommended as an intervention strategy to
      reduce microbial risks associated to irrigation water. Commercial water
      treatments mostly depend on chemical agents; although growers search for greener
      alternatives to chemical biocides. Ultrasounds (US) have been proposed as an
      environmentally friendly technology for irrigation water. In the present study,
      the suitability of two US treatments (20kHz: US20 and 40kHz: US40 at a specific
      energy (Es) of 745J/L) and one chlorine treatment (1-2ppm free chlorine) was
      evaluated and compared to the untreated control. Five water reservoirs belonging
      to five commercial intensive farms were selected as representative of irrigation
      practices generally used in south of Europe. All tested water treatments were
      able to reduce microbial loads, including Escherichia coli (0.5-0.6 log units),
      to values that were accepted in most of the recommended guidelines of good
      agricultural practices (<=2logunits). The obtained reductions were lower than
      those previously reported for these water treatment technologies in lab-scale
      tests. High microbial reductions are commonly obtained in laboratory studies,
      yielding impressive results. However, when the same treatments are applied under
      real commercial conditions, microbial reductions are usually less impressive. All
      water treatments were able to reduce COD of irrigation water when compared to the
      untreated control. COD reductions obtained using chlorine (>=430mg/L) and US 20
      (~100mg/L) were higher than those observed using US 40 (<50mg/L). The impact of
      the water quality on the efficacy of US treatments was evaluated in two types of
      water including surface water and treated wastewater. It was found that the
      quality of the irrigation water significantly influences the efficacy of the
      ultrasound treatment. Correlations between indicator parameters have been also
      evaluated. Obtained results showed that high algae counts were well correlated
      with high levels of coliforms and E. coli. It could be concluded that US can be
      proposed as an alternative water treatment to chemical treatments to preserve
      microbial quality of irrigation water stored in water reservoirs reducing the
      environmental impact.

PMID- 28454942
TI  - Sugar reduction in probiotic chocolate-flavored milk: Impact on dynamic sensory
      profile and liking.
AB  - Reducing the sugar content of processed products has been claimed to be one of
      the most efficient strategies for decreasing sugar intake. The present work aimed
      at studying the influence of sugar reduction on the dynamic sensory profile and
      consumers' liking of probiotic chocolate-flavored milks using a novel temporal
      methodology, and to evaluate two alternatives (vanilla flavor and thaumatin) to
      attenuate the sensory changes caused by sugar reduction. Probiotic chocolate
      flavored milks were formulated with different reductions in added sugar (0, 20,
      40 and 60%). Vanilla flavor and thaumatin were added to the sugar-reduced samples
      at two concentrations. Samples were evaluated by trained assessors using Temporal
      check-all-that-apply (TCATA). Additionally, consumers evaluated the dynamic
      sensory profile of a subset of the samples using TCATA and indicated their
      overall liking using a 9-point hedonic scale. Results from the present work
      showed that the main effect of sugar reduction on the dynamic sensory profile of
      the probiotic chocolate-flavored milks was related to changes in sweetness,
      bitterness and thickness. A reduction in added sugar of 20% led to changes in
      sweetness intensity, which were perceived by both trained assessors and
      consumers. However, consumers' liking was not significantly affected by sugar
      reduction up to 40%. The addition of vanilla flavor at suprathreshold
      concentrations was not efficient in increasing sweetness perception in chocolate
      flavored milks with the lowest sugar reduction percentage, suggesting that it may
      not be a feasible alternative for reducing sugar in this product category. These
      results suggest that in many situations sugar content of food products could be
      decreased without a relevant impact on consumers' sensory and hedonic perception.

PMID- 28454943
TI  - Nanocomplexation of soy protein isolate with curcumin: Influence of ultrasonic
      treatment.
AB  - Soy protein isolate (SPI) can act as effective nanocarriers for water-insoluble
      curcumin, however, the maximal capacity of this protein to load curcumin and
      molecular mechanism for the formation of the nanocomplexes are still little
      known. This work investigated the formation and properties of SPI-curcumin
      nanocomplexes formed at a low concentration of 0.05% (w/v), as well as the
      influence of a high intensity ultrasonic treatment on the nanocomplexation. Most
      of the particles in non- or ultrasonic-treated SPIs were present in nanoparticle
      form with z-average sizes of about 50-52nm. The load amount (LA) of curcumin in
      the non-treated nanocomplexes reached 103.9MUg/mg SPI. The ultrasonic treatment
      of the protein solution further significantly increased the LA, while the LA was
      considerably decreased by the treatment after the nanocomplexation. The
      complexation with curcumin significantly increased the particle size and zeta
      potential of both non- and ultrasonic-treated SPIs, but led to a considerable
      reduction in surface hydrophobicity, with the greater changes observed for
      ultrasonic-treated SPI. The nanocomplexation with SPIs remarkably improved the
      storage stability of curcumin, with much better improvement observed for the
      ultrasonic-treated SPI. Both the number and nature of hydrophobic sites are
      important for the nanoparticles in SPI to exhibit high capacity to load curcumin
      molecules. This study confirmed that SPI exhibited a high capacity to load water
      insoluble curcumin, and an ultrasonic pretreatment could further improve its
      encapsulation efficiency and stability of curcumin.

PMID- 28454944
TI  - Digestibility and structural parameters of spray-dried casein clusters under
      simulated gastric conditions.
AB  - The digestibility of casein clusters prepared from sodium caseinate solution
      (plain or pH-adjusted (pH=6.0)) was studied. The prepared solutions were spray
      dried at different inlet air temperatures (150 degrees C and 180 degrees C), and
      the properties (i.e. encapsulation efficiency, surface hydrophobicity, and
      digestibility) of the resultant powders were investigated. The specimens obtained
      from the pH-adjusted solution had higher encapsulation efficiencies than the
      specimens obtained from the plain solution. A higher spray-drying temperature
      resulted in lower encapsulation efficiencies and higher surface hydrophobicities.
      Simulated gastric digestion tests were carried out to study the digestibility of
      the obtained casein clusters, which was analyzed in terms of reaction kinetics
      and structural changes during digestion. The effects of drying temperature and pH
      on the amount of casein digested were not significant; that is, approximately 30%
      of casein was digested in 120min for all specimens. Small-angle and ultra-small
      angle X-ray scattering measurements were used to analyze the structure of the
      obtained clusters and their changes during digestion. The results suggested that
      all the obtained casein clusters, with an average size of approximately 428nm,
      had a rough, fractal-structured surface with many dense primary clusters. These
      structures changed during digestion; specifically, the cluster size increased
      both in the overall diameter and on the primary structure scale. The fractal
      characteristics changed from surface to mass fractals, and simultaneously, the
      cluster density decreased. The drying temperature affected the cluster size
      during digestion, and the trends were different in the specimens obtained from
      the plain and pH-adjusted solutions. These results could be useful in the design
      of protein-based encapsulation systems with desirable digestibility and
      bioavailability.

PMID- 28454945
TI  - Predicting chemical degradation during storage from two successive concentration
      ratios: Theoretical investigation.
AB  - When a vitamin's, pigment's or other food component's chemical degradation
      follows a known fixed order kinetics, and its rate constant's temperature
      dependence follows a two parameter model, then, at least theoretically, it is
      possible to extract these two parameters from two successive experimental
      concentration ratios determined during the food's non-isothermal storage. This
      requires numerical solution of two simultaneous equations, themselves the
      numerical solutions of two differential rate equations, with a program especially
      developed for the purpose. Once calculated, these parameters can be used to
      reconstruct the entire degradation curve for the particular temperature history
      and predict the degradation curves for other temperature histories. The concept
      and computation method were tested with simulated degradation under rising and/or
      falling oscillating temperature conditions, employing the exponential model to
      characterize the rate constant's temperature-dependence. In computer simulations,
      the method's predictions were robust against minor errors in the two
      concentration ratios. The program to do the calculations was posted as freeware
      on the Internet. The temperature profile can be entered as an algebraic
      expression that can include 'If' statements, or as an imported digitized time
      temperature data file, to be converted into an Interpolating Function by the
      program. The numerical solution of the two simultaneous equations requires close
      initial guesses of the exponential model's parameters. Programs were devised to
      obtain these initial values by matching the two experimental concentration ratios
      with a generated degradation curve whose parameters can be varied manually with
      sliders on the screen. These programs too were made available as freeware on the
      Internet and were tested with published data on vitamin A.

PMID- 28454946
TI  - Physical stability of emulsion encapsulated in alginate microgel particles by the
      impinging aerosol technique.
AB  - Emulsion filled alginate microgel particles can be applied as carrier systems for
      lipophilic actives in pharmaceutical and food formulations. In this study, the
      effects of oil concentration, emulsifier type and oil droplet size on the
      physical stability of emulsions encapsulated in calcium alginate microgel
      particles (20-80MUm) produced by a continuous impinging aerosol technique were
      studied. Oil emulsions emulsified by using either sodium caseinate (SCN) or Tween
      80 were encapsulated at different oil concentrations (32.55, 66.66 and 76.68% w/w
      of total solids content). The emulsions were analysed before and after
      encapsulation for changes in emulsion size distribution during storage, and
      compared to unencapsulated emulsions. The size distribution of encapsulated fine
      emulsion (mean size ~0.20MUm) shifted to a larger size distribution range during
      encapsulation possibly due to the contraction effect of the microgel particles.
      Coarse emulsion droplets (mean size ~18MUm) underwent a size reduction during
      encapsulation due to the shearing effect of the atomizing nozzle. However, no
      further size changes in the encapsulated emulsion were detected over four weeks.
      The type of emulsifier used and emulsion concentration did not significantly
      affect the emulsion stability. The results suggest that the rigid gel matrix is
      an effective method for stabilising lipid emulsions and can be used as a carrier
      for functional ingredients.

PMID- 28454947
TI  - Modeling the protective effect of aw and fat content on the high pressure
      resistance of Listeria monocytogenes in dry-cured ham.
AB  - High pressure processing (HPP) is a promising food preservation technology as an
      alternative to thermal processing for microbial inactivation. The technological
      parameters, the type of microorganism, and the food composition can greatly
      affect the microbicidal potential of HPP against spoilage and pathogenic
      microorganisms. Presently, the number of available models quantifying the
      influence of food characteristics on the pathogen inactivation is scarce. The aim
      of this study was to model the inactivation of Listeria monocytogenes CTC1034 in
      dry-cured ham, as a function of pressure (347-852MPa, 5min/15 degrees C), water
      activity (aw, 0.86-0.96) and fat content (10-50%) according to a Central
      Composite Design. The response surface methodology, based on the equation
      obtained with a stepwise multivariate linear regression, was used to describe the
      relationship between bacterial inactivation and the studied variables. According
      to the best fitting polynomial equation, besides pressure intensity, both aw and
      fat content exerted a significant influence on HP-inactivation of L.
      monocytogenes. A clear linear piezoprotection trend was found lowering the aw of
      the substrate within the whole range of tested pressure. Fat content was included
      in the model through the quadratic term and as interaction term with pressure,
      resulting in a particular behavior. A protective effect due to the presence of
      high fat content was identified for pressure treatments above ca. 700MPa. At
      lower pressure, higher inactivation of L. monocytogenes occurred by increasing
      the fat content above 30%. The results emphasize the relevant influence of
      intrinsic factors on the L. monocytogenes inactivation by HPP, making necessary
      to assess and validate the effectiveness of HPP on specific food products and
      consequently set process criteria adjusted to each particular food product.

PMID- 28454948
TI  - Reactions of polyphenols in masticated apple fruit with nitrite under stomach
      simulating conditions: Formation of nitroso compounds and thiocyanate conjugates.
AB  - By the ingestion of fresh apple fruit, it is masticated squeezing apple juice
      into the oral cavity and the juice is mixed with saliva. The mixture of saliva
      and apple juice is swallowed into the stomach where the pH is around 2. This
      paper deals with the reactions of polyphenols in the juice obtained by
      mastication of apple fruit with salivary nitrite under acidic conditions. The
      concentrations of catechins, procyanidins, and chlorogenic acid in the apple
      juice were approximately 55, 55, and 170MUM, respectively, and the polyphenols
      were oxidized by salivary nitrite under conditions of the stomach. Rates of the
      oxidation increased in order chlorogenic acid<catechins<procyanidins. The
      oxidation of catechins and procyanidins resulted in the formation of the nitroso
      compounds, and the oxidation of chlorogenic acid resulted in the formation of the
      thiocyanate conjugate. The production of dinitroso compounds is proposed to be
      due to the addition of nitric oxide (NO) to radicals of catechins and
      procyanidins. As the mechanism of thiocyanate conjugate formation, reaction of o
      quinone of chlorogenic acid with a salivary component thiocyanate is proposed,
      and the formation of the thiocyanate conjugate is discussed from the point of
      detoxification of chlorogenic acid quinone.

PMID- 28454949
TI  - Wheat bread aroma compounds in crumb and crust: A review.
AB  - Bread is one of the most widely consumed foods in the world. Among the different
      properties that define its quality, the aroma of bread is considered essential to
      its approval by consumers. Knowing what the compounds found in bread are, as well
      as the most important ones in crumb and crust, and understanding their biological
      sources and how they affect the final aroma of bread, could make it possible to
      modify the steps of bread manufacturing in order to enhance those with a positive
      impact and reduce those with a negative impact. The aim of this review is to
      provide a guideline correlating a great deal of the information now available
      regarding wheat bread aroma. For this purpose, a total of 326 volatile compounds
      reported in the literature have been included. The sensorial correlation of these
      compounds with the final aroma of wheat bread has also been explained, as well as
      the biological sources that generate them. Finally, it is shown how modifying the
      production stages of wheat bread could also affect the odour quality.

PMID- 28454950
TI  - First evaluation of the antimutagenic effect of mangaba fruit in vivo and its
      phenolic profile identification.
AB  - The chemical composition and functional effects of mangaba fruit pulp were
      evaluated through a multi-endpoint assay in mice, consisting of the bone marrow
      micronucleus test, gut micronucleus test, and the apoptosis, oxidative stress,
      and comet assays. Mangaba fruit pulp was administered in three doses, 10, 20, and
      40ml/kg body weight (b.w.), by gavage to male Swiss mice against doxorubicin and
      dimethylhydrazine-induced mutagenicity. The phenolic profile of the mangaba fruit
      pulp was evaluated by HPLC, and seven compounds were identified: gallic acid,
      catechin, chlorogenic acid, vanillic acid, o-coumaric acid, rosmarinic acid, and
      rutin. The in vivo tests revealed that mangaba fruit pulp showed no
      toxic/mutagenic effects in any of the assays performed, and also showed
      protective effects at all endpoints. At the three administered extract
      concentrations, the main results about the protective effects were as follows:
      bone marrow micronucleus test (42.33, 58.14, and 77.21%), micronucleus gut test
      (34.21, 63.15, and 78.07%), and apoptosis index (57.5, 43.68, and 65.52%). This
      study provides scientific evidence for the antimutagenic potential of mangaba
      fruit pulp and emphasizes its potential as a functional food with widespread
      applicability in the food industry.

PMID- 28454951
TI  - Does food complexity have a role in eliciting expectations of satiating capacity?
AB  - New strategies for formulating healthy, balanced food with enhanced expected
      satiating capacity are a hot topic. The present work tests the hypothesis that
      adding complexity to food will result in higher expectations of satiating
      capacity. Different kinds of "visible" particles (wheat bran, ground coconut,
      flaxseeds and oat meal) were added to cheese pies with the aim of increasing the
      complexity of both their appearance and their texture. Two more basic recipes
      were also prepared with no particles added. Instrumental texture measurements,
      complexity and expected satiating capacity consumer scoring and sensory profiling
      of the six pie formulations were performed. In addition, the consumers were asked
      to write down the characteristics they took into account in their pie complexity
      scores. For pies with very similar instrumental TPA hardness and resistance to
      penetration values, a clear trend that emerged was that the more complex the
      texture, the higher the satiating capacity expectations. The qualitative analysis
      of the terms mentioned by consumers was of great value for understanding the
      concepts underlying the appraisal of the samples' complexity.

PMID- 28454952
TI  - The challenge of challenge testing to monitor Listeria monocytogenes growth on
      ready-to-eat foods in Europe by following the European Commission (2014)
      Technical Guidance document.
AB  - European Regulation (EC) No. 2073/2005 lays down the microbiological criteria for
      certain microorganisms in foods and the implementing rules to be complied with by
      food business operators (FBOs) in Europe when implementing general and specific
      hygiene measures. In relation to Listeria monocytogenes, this regulation covers
      primarily ready-to-eat (RTE) food products, and requires different
      microbiological criteria depending on the ability of the food product to support
      growth of L. monocytogenes. In addition, this regulation establishes that food
      safety is the responsibility of the FBO. The FBO can conduct studies to evaluate
      the growth of L. monocytogenes that may be present in the product during the
      shelf-life under reasonably foreseeable storage conditions of distribution,
      storage and use in order to investigate compliance with the criteria throughout
      the shelf-life of the product. The European Union Community Reference Laboratory
      for L. monocytogenes published a revised technical guidance document in June 2014
      for conducting shelf-life studies on L. monocytogenes in RTE foods. This review
      article describes the recently published European guidance document, with special
      focus on the design of challenge studies to determine the growth potential of L.
      monocytogenes on foods. Information is given particularly on what a challenge
      test is and when one is advisable. The factors to be considered and the
      laboratory methodology to be applied when performing a challenge test to
      determine the growth potential of L. monocytogenes in a defined food matrix are
      also described. Results of recent research articles applying challenge tests to
      determine the growth of L. monocytogenes in a range of foodstuffs are summarized
      and discussed. Finally, recommendations for obtaining data that can contribute to
      any further revision of the guidance document and for addressing the main
      challenges of challenge testing for FBOs are presented.

PMID- 28454953
TI  - Cross-linking proteins by laccase: Effects on the droplet size and rheology of
      emulsions stabilized by sodium caseinate.
AB  - The aim of this work was to evaluate the influence of laccase and ferulic acid on
      the characteristics of oil-in-water emulsions stabilized by sodium caseinate at
      different pH (3, 5 and 7). Emulsions were prepared by high pressure
      homogenization of soybean oil with sodium caseinate solution containing varied
      concentrations of laccase (0, 1 and 5mg/mL) and ferulic acid (5 and 10mM).
      Laccase treatment and pH exerted a strong influence on the properties with a
      consequent effect on stability, structure and rheology of emulsions stabilized by
      Na-caseinate. At pH7, O/W emulsions were kinetically stable due to the negative
      protein charge which enabled electrostatic repulsion between oil droplets
      resulting in an emulsion with small droplet size, low viscosity, pseudoplasticity
      and viscoelastic properties. The laccase treatment led to emulsions showing shear
      thinning behavior as a result of a more structured system. O/W emulsions at pH5
      and 3 showed phase separation due to the proximity to protein pI, but the laccase
      treatment improved their stability of emulsions especially at pH3. At pH3, the
      addition of ferulic acid and laccase produced emulsions with larger droplet size
      but with narrower droplet size distribution, increased viscosity,
      pseudoplasticity and viscoelastic properties (gel-like behavior). Comparing
      laccase treatments, the combined addition of laccase and ferulic acid generally
      produced emulsions with lower stability (pH5), larger droplet size (pH3, 5 and 7)
      and higher pseudoplasticity (pH5 and 7) than emulsion with only ferulic acid. The
      results suggested that the cross-linking of proteins by laccase and ferulic acid
      improved protein emulsifying properties by changing functional mechanisms of the
      protein on emulsion structure and rheology, showing that sodium caseinate can be
      successfully used in acid products when treated with laccase.

PMID- 28454954
TI  - Pressurized aqueous ethanol extraction of beta-glucans and phenolic compounds
      from waxy barley.
AB  - Beta-glucans and phenolics were extracted from waxy barley using pressurized
      aqueous ethanol in a stirred batch reactor at 25bar and 500rpm. The effect of
      temperature (135-175 degrees C), extraction time (15-55min) and ethanol content
      (5-20%) was evaluated. Temperature had an opposite effect on the extraction of
      both compounds. The higher the temperature, the lower the beta-glucan extraction
      yield due to fragmentation, but a significant increase on the phenolic recovery
      was observed. Long extraction times favored the extraction of beta-glucans at low
      temperatures and phenolics at any temperature. The ethanol content was not
      statistically significant on the beta-glucan extraction, but helped to maintain
      the molecular weight of the extracted beta-glucan. To obtain liquid extracts rich
      in high molecular weight beta-glucans and phenolics, mild conditions of 151
      degrees C, 21min and 16% ethanol are needed, leading to 51% beta-glucan
      extraction yield with a molecular weight of 500-600kDa and 5mgGAE/g barley.

PMID- 28454955
TI  - Effects of defoliation on quality attributes of Nero di Troia (Vitis vinifera L.)
      grape and wine.
AB  - Field studies were conducted in Puglia (Italy) to evaluate the influence of
      defoliation around cluster zones on grape and wine quality. Nero di Troia grapes
      were subjected to four different treatments: N: no leaf removal; E: leaf removal
      in the area of the clusters along the east side (at complete veraison); E/W: leaf
      removal in the area of the clusters along the east and west side (at complete
      veraison); and F: almost complete leaf removal along the west side (at complete
      veraison) and at pre-harvest also along the east side. Grapes of defoliated vines
      generally showed higher sugar content, lower titratable acidity, total
      flavonoids, flavonoids different from anthocyanins, and total phenolic content
      than grapes from non-defoliated vines while their total anthocyanin concentration
      was not affected by defoliation at a significant level. Concerning wines, alcohol
      content, residual soluble solids, different forms of anthocyanins but also
      volatile acidity were generally higher in samples from defoliated vines.
      Differences were also highlighted among the defoliation treatments: the best
      results in terms of dry matter, sugar and alcohol content were observed in the
      samples submitted to the more severe defoliation as a consequence of the higher
      light availability and berry temperature. Concerning the concentration of the
      individual phenolics, significant differences were highlighted for: caffeic and
      caftaric acids, peonidin- and malvidin-3-p-coumaroylglucoside, which were higher
      in the E wines; quercetin-3-glucoside, galactoside, and rhamnoside, and
      procyanidins, which were higher in F wines.

PMID- 28454956
TI  - The existence of optimistic bias about foodborne disease by food handlers and its
      association with training participation and food safety performance.
AB  - A positive outlook regarding future events, in which individuals find themselves
      less likely than others to experience negative events, is called optimistic bias
      (OB). The aims of this study were: 1. To ascertain the existence and measure the
      OB phenomenon in food handlers in relation to foodborne disease and 2. To examine
      the association of OB with food handlers' risk perceptions, knowledge, attitudes,
      self-reported practices, training participation, food safety performance of the
      establishments and microbiological analysis. This study examined different food
      businesses in Santos city, in Brazil, as follows: street food kiosks, beach
      kiosks, restaurants, hospitals, and school meal services. The food handlers
      indicated their own risk and their peers' risk of causing a foodborne disease.
      Responses were given on a 10cm linear scale anchored with descriptors of
      intensity ranging from "none" to "very high". The difference between these risk
      perceptions characterized a score of tendency of an OB. A structured
      questionnaire was administered to evaluate knowledge, attitudes, self-reported
      practices and food safety performance. A total of 183 food handlers participated
      in the study. Microbiological analyses were conducted with ready-to-eat
      foods/preparations from selected sites. The food handlers perceived themselves as
      less likely than their peers to cause a foodborne disease (p<0.001),
      demonstrating the tendency of an OB. Food handlers who had undergone some
      training presented lower scores for the perceived risk of themselves being
      responsible for a foodborne disease and higher knowledge than did untrained
      individuals. Hospitals, schools and restaurants performed better than street food
      group considering food safety performance. However, microorganisms were found in
      food samples from hospitals. This result may be motivated by OB and other
      subjective factors. Apparently, this positive outlook of food handlers is
      associated with training participation, lethality perception and correlating
      positively with age. No association was found between OB scores and knowledge,
      attitudes and self-reported practices. Since OB may lead individuals to adopt
      inappropriate or dangerous behavior, strategies for debiasing food handlers
      should be designed.

PMID- 28454957
TI  - The use of statistical software in food science and technology: Advantages,
      limitations and misuses.
AB  - Strict requirements of scientific journals allied to the need to prove the
      experimental data are (in)significant from the statistical standpoint have led to
      a steep increase in the use and development of statistical software. In this
      aspect, it is observed that the increasing number of software tools and packages
      and their wide usage has created a generation of 'click and go' users, who are
      eagerly destined to obtain the p-values and multivariate graphs (projection of
      samples and variables on the factor plane), but have no idea on how the
      statistical parameters are calculated and the theoretical and practical reasons
      he/she performed such tests. However, in this paper, some published examples are
      listed and discussed in detail to provide a holistic insight (positive points and
      limitations) about the uses and misuses of some statistical methods using
      different available statistical software. Additionally, a brief description of
      several commercial and free statistical software is made highlighting their
      advantages and limitations.

PMID- 28454958
TI  - Identification of odour-active compounds of pasteurised orange juice using
      multidimensional gas chromatography techniques.
AB  - Odour-active compounds present in pasteurised orange juice were identified by gas
      chromatography-olfactometry (GC-O) employing heart-cut multidimensional GC
      techniques with olfactometry (O) and mass spectrometry (H/C MDGC-O/MS) and
      comprehensive two-dimensional gas chromatography-accurate mass time-of-flight MS
      (GC*GC-accTOFMS). Headspace solid phase microextraction sampling proved to be
      qualitatively adequate for the analysis of pasteurised orange juice. The GC-O
      approach distinguished 13 potent odour regions (detection frequency>=3) in the
      orange juice extract, in which 7 regions were then subjected to detailed
      identification of the compounds that contribute to the odour, by using higher
      resolution H/C MDGC-O/MS. This analysis permitted the odour-active peaks to be
      better resolved on the 2D column, with removal from background matrix, for the
      seven regions. GC*GC-FID and GC*GC-accTOFMS reveal the overall complexity of the
      volatile compounds in the product and assisted in assignment of the isolated
      peaks of the odour-active compounds, confirming the identification in a number of
      cases. Four aldehydes (hexanal, heptanal, octanal, citral), 2 esters (ethyl
      butanoate, methyl hexanoate), and 4 monoterpenes (alpha-pinene, D-limonene,
      linalool, alpha-terpineol) were confirmed in accordance with olfactometry
      assessment in the processed juice. This multi-assessment instrument approach of
      GC-O, GC*GC, and H/C MDGC provided an effective insight into the processed orange
      juice aroma.

PMID- 28454959
TI  - Mode of pancreatic lipase inhibition activity in vitro by some flavonoids and non
      flavonoid polyphenols.
AB  - Numerous reports have shown plant metabolites as potential inhibitors of
      pancreatic lipase (PL). The most notable group is plant polyphenols. However, a
      limited number of reports diagnosed their mode of inhibition delineating
      conflicting results. To elucidate the kinetic mode of PL inhibition, some
      selected flavonoid and non-flavonoid polyphenol standards were first screened for
      their lipase inhibition potency by their half maximal inhibitory concentration
      (IC50) followed by inhibition kinetic analysis. Of the phenolics tested, only
      gallic acid (GA) and galloyl moiety containing epicatechin, viz.,
      epigallocatechin (EGC) and epigallocatechin gallate (EGCG) showed, comparative to
      others, higher PL inhibitions (IC50, 387.2, 237.3, and 391.2MUM respectively).
      Analysis of enzyme inhibition modalities at various substrate concentrations
      revealed a dose-dependent inhibition of reaction velocity. Inhibitory rates
      decreased by the order of EGCG>EGC>GA (Ki, 13.29>35.0>44.61MUM respectively). The
      results, when verified by visual inspection of Lineweaver-Burk as well as Dixon
      plots, showed inhibitions of PL by GA, EGC, and EGCG that were best fit to
      competitive inhibitions. A role of the galloyl moiety in enzyme-inhibitor binding
      has been evident from their structural resemblance. Depicting it further, ethyl
      gallate (EG), showed a similar competitive inhibition, therefore, indicating a
      galloyl moiety driven competitive inhibition of PL.

PMID- 28454960
TI  - Study of chemical changes in pasteurised orange juice during shelf-life: A
      fingerprinting-kinetics evaluation of the volatile fraction.
AB  - The current work used fingerprinting-kinetics for the first time to monitor shelf
      life changes in a low-pH, pasteurised, shelf-stable product, more particular in
      orange juice. Orange juice samples were stored as a function of time at four
      different storage temperatures (20, 28, 35 and 42 degrees C). To obtain insight
      into chemical changes in the volatile food fraction, samples were fingerprinted
      with headspace GC-MS. The objectives of this work were twofold: (i) to identify
      major chemical changes of pasteurised orange juice during shelf-life and (ii) to
      study the kinetics of selected shelf-life compounds in the context of accelerated
      shelf-life testing (ASLT). At 20 degrees C, changes in terpenes and a decrease in
      aldehydes were observed. Oxides and sulphur compounds increased and esters
      decreased at increased storage temperatures (at 28 degrees C and above).
      Concerning ASLT, four volatile compounds had clear temperature and time dependent
      kinetics within the investigated temperature range.

PMID- 28454961
TI  - Proteomic and high-throughput analysis of protein expression and microbial
      diversity of microbes from 30- and 300-year pit muds of Chinese Luzhou-flavor
      liquor.
AB  - Luzhou-flavor liquor is fermented based on the metabolism of special microbial
      communities in pit. In this study, total proteins and DNAs of microbes from 30-
      and 300-year pit muds were firstly extracted. Meanwhile, an efficient approach
      for protein extraction with increased protein content was optimized. iTRAQ-based
      proteomic was then applied to investigate the aroma-forming functional protein
      expression of microbes from the samples. Furthermore, high-throughput sequencing
      of 16S rDNA was employed to reveal microbial diversity. We comparatively
      identified 63 proteins of aroma-forming functional microbes in these samples, and
      found that 59 of these proteins were highly expressed in the 300-year pit mud.
      Those aroma-forming functional proteins were found to be involved in
      methanogenesis, as well as the formation of caproic acid and butyric acid during
      the liquor fermentation. High-throughput sequencing revealed that the microbes
      most commonly found in both samples were members of phylum Firmicutes (by 97%
      sequence similarity), both of which, along with another common Methanobacterium,
      were important components of aroma-forming functional colonies in the pit muds
      for the brewing of Chinese liquor. The findings in this study afford us new
      insight into the different protein expression levels and microbial communities in
      two pit muds.

PMID- 28454962
TI  - Chemical characterization and antioxidant capacity of the araca-pera (Psidium
      acutangulum): An exotic Amazon fruit.
AB  - The "araca-pera" (Psidium acutangulum DC) is an exotic guava consumed by the
      Brazilian Amazon population. This paper describes 22 compounds from this fruit by
      UHPLC-HRMS and NMR methods, being one disaccharide, five monosaccharides, two
      organic acids, one trihydroxycinnamic acid glucopyranosyl, one tannine digalloyl
      glucopyranosyl, five triterpenoid acids, and six fatty acids. It also quantifies
      the level of ascorbic acid (AA) by HPLC-MS (74.32+/-1.23mg/100g of fresh fruit),
      and defines the chemical antioxidant activities by DPPH and ABTS+ assays (24.96+/
      0.75, 90.57+/-0.63mg of vitamin C/100g fresh fruit, respectively), and a cell
      based assays (76-100%). These results have shown that this exotic guava can be
      consumed as a nutraceutical ingredient, as well as be used in the production of
      functional foods in the Amazonian diet to prevent chronic and oxidative diseases.

PMID- 28454963
TI  - Effects of dicarbonyl trapping agents, antioxidants, and reducing agents on the
      formation of furan and other volatile components in canned-coffee model systems.
AB  - The formation of furan and certain volatiles related to furan formation
      mechanisms was studied using gas chromatography-mass spectrometry combined with
      solid-phase micro extraction after adding dicarbonyl trapping agents [epicatechin
      (EC), epigallocatechin gallate (EGCG), and catechin], water-soluble antioxidants
      (Trolox, caffeic acid, ferulic acid, and chlorogenic acid), fat-soluble
      antioxidants (alpha-tocopherol, BHT, and beta-carotene), and reducing agents
      (glutathione and sodium sulfite) to canned-coffee model systems (CMS). The level
      of furan formation decreased significantly following the addition of EC (by
      65.3%), EGCG (by 60.0%), and catechin (by 44.7%). In addition, the formation of
      Maillard reaction products, including furan derivatives (furfural and 5
      methylfurfural), Strecker aldehyde (2-methylbutanal), pyrazines (2,6
      dimethylpyrazine), and lipid oxidation products (including hexanal and 2
      pentylfuran) was suppressed when any of the dicarbonyl trapping agents was added.
      Among the water-soluble antioxidants studied, chlorogenic acid most significantly
      decreased the furan level, by 67.0%, followed by ferulic acid (57.6%), Trolox
      (50.1%), and caffeic acid (48.2%) in the CMS. Chlorogenic acid also reduced the
      formation of furfural and lipid oxidation products. However, the addition of
      caffeic acid, ferulic acid, and chlorogenic acid decreased the generation of key
      coffee aroma components, such as Strecker aldehydes (2-methylpropanal and 2
      methylbutanal), 5-methylfurfural, and pyrazines (2,6-dimethylpyrazine and 2-ethyl
      5-methylpyrazine). Among the fat-soluble antioxidants, BHT and alpha-tocopherol
      decreased the furan level by 49.3% and 39.3%, respectively, while beta-carotene
      increased the furan level by 34.8%. The addition of sodium sulfite and
      glutathione to CMS also led to considerable reductions in furan, of 64.1% and
      44.9%, respectively.

PMID- 28454964
TI  - Influence of the temperature and oxygen exposure in red Port wine: A kinetic
      approach.
AB  - Although phenolics are recognized to be related with health benefits by limiting
      lipid oxidation, in wine, they are the primary substrates for oxidation resulting
      in the quinone by-products with the participation of transition metal ions.
      Nevertheless, high quality Port wines require a period of aging in either bottle
      or barrels. During this time, a modification of sensory properties of wines such
      as the decrease of astringency or the stabilization of color is recognized to
      phenolic compounds, mainly attributed to anthocyanins and derived pigments. The
      present work aims to illustrate the oxidation of red Port wine based on its
      phenolic composition by the effect of both thermal and oxygen exposures. A
      kinetic approach toanthocyanins degradation was also achieved. For this purpose a
      forced red Port wine aging protocol was performed at four different storage
      temperatures, respectively, 20, 30, 35 and 40 degrees C, and two adjusted oxygen
      saturation levels, no oxygen addition (treatment I), and oxygen addition
      (treatment II). Three hydroxycinnamic esters, three hydroxycinnamic acids, three
      hydroxybenzoic acids, two flavan-3-ols, and six anthocyanins were quantitated
      weekly during 63days, along with oxygen consumption. The most relevant phenolic
      oxidation markers were anthocyanins and catechin-type flavonoids, which had the
      highest decreases during the thermal and oxidative red Port wine process. Both
      temperature and oxygen treatments affected the rate of phenolic degradation. In
      addition, temperature seems to influence mostly the phenolics kinetic
      degradation.

PMID- 28454965
TI  - Impact of a food-grade cationic biopolymer (epsilon-polylysine) on the digestion
      of emulsified lipids: In vitro study.
AB  - epsilon-Polylysine (epsilon-PL) is a cationic biopolymer that may be used as a
      food ingredient because of its strong antimicrobial activity and potential to
      inhibit pancreatic lipase. We examined the effect of polylysine on the digestion
      of corn oil-in-water emulsions stabilized by either a natural anionic surfactant
      (quillaja saponin) or a synthetic non-ionic surfactant (Tween 20). Emulsions were
      prepared using high pressure homogenization (microfluidization) and then
      subjected to in vitro digestion in the absence or presence of polylysine at the
      maximum level allowed in foods by the FDA. Samples were characterized before and
      after in vitro digestion using electrophoresis, confocal microscopy, and static
      light scattering. The presence of polylysine decreased the hydrolytic activity of
      pancreatic lipase by around 53% and 28% in the Tween 20- and saponin-stabilized
      emulsions, respectively. The lipase-inhibiting properties of cationic polylysine
      were attributed to its electrostatic interaction with anionic components, such as
      bile salts, free fatty acids, and digestive enzymes. These results have important
      implications for the incorporation of polylysine into food systems, particularly
      those containing lipophilic nutrients.

PMID- 28454966
TI  - Conducting starter culture-controlled fermentations of coffee beans during on
      farm wet processing: Growth, metabolic analyses and sensorial effects.
AB  - In this study, the potential use of Pichia fermentans YC5.2 as a starter culture
      to conduct controlled coffee bean fermentations during on-farm wet processing was
      investigated. Inoculated fermentations were conducted with or without the
      addition of 2% (w/v) sucrose, and the resultant microbial growth and metabolism,
      bean chemistry and beverage quality were compared with spontaneous (control)
      fermentation. In both inoculated treatments, P. fermentans prevailed over
      indigenous microbiota and a restricted microbial composition was observed at the
      end of fermentation process. The inoculation also increased the production of
      specific volatile aroma compounds (e.g., ethanol, acetaldehyde, ethyl acetate and
      isoamyl acetate) and decreased the production of lactic acid during the
      fermentation process. Sucrose supplementation did not significantly interfere
      with the growth and frequency of P. fermentans YC5.2 inoculum but maintained high
      levels of wild bacteria population and lactic acid production similar to the
      spontaneous process. In roasted beans, the content of sugars and organic acids
      were statistically (p<0.05) similar for all the treatments. However, the
      inoculated fermentations were shown to influence the volatile fraction of roasted
      coffee beans by increasing the concentration of yeast-derived metabolites
      compared to control. Sensory analysis of coffee beverages demonstrated that the
      use of the YC5.2 strain was favorable for the production of high-quality coffees
      with distinctive characteristics, e.g., intense perception of 'vanilla' taste and
      'floral' aromas. In conclusion, the use of P. fermentans YC5.2 in coffee
      processing was shown to be a viable alternative to control the fermentation step
      and to ensure consistent quality of finished products.

PMID- 28454967
TI  - Ultra-High Pressure Homogenization enhances physicochemical properties of soy
      protein isolate-stabilized emulsions.
AB  - The effect of Ultra-High Pressure Homogenization (UHPH, 100-300MPa) on the
      physicochemical properties of oil-in-water emulsions prepared with 4.0% (w/v) of
      soy protein isolate (SPI) and soybean oil (10 and 20%, v/v) was studied and
      compared to emulsions treated by conventional homogenization (CH, 15MPa). CH
      emulsions were prepared with non-heated and heated (95 degrees C for 15min) SPI
      dispersions. Emulsions were characterized by particle size determination with
      laser diffraction, rheological properties using a rotational rheometer by
      applying measurements of flow curve and by transmission electron microscopy. The
      variation on particle size and creaming was assessed by Turbiscan(r) analysis,
      and visual observation of the emulsions was also carried out. UHPH emulsions
      showed much smaller d3.2 values and greater physical stability than CH emulsions.
      The thermal treatment of SPI prior CH process did not improve physical stability
      properties. In addition, emulsions containing 20% of oil exhibited greater
      physical stability compared to emulsions containing 10% of oil. Particularly,
      UHPH emulsions treated at 100 and 200MPa with 20% of oil were the most stable due
      to low particle size values (d3.2 and Span), greater viscosity and partial
      protein denaturation. These results address the physical stability improvement of
      protein isolate-stabilized emulsions by using the emerging UHPH technology.

PMID- 28454968
TI  - Volunteer study and serum protein profiling to understand inflammatory response
      induced by Satsuma mandarin.
AB  - It has been observed that consumption of a certain amount of Satsuma, lychee, and
      longan often caused a symptom characterized by dry or sore throat, gum swelling
      and even mouth ulcer, which significantly impaired the life quality of a large
      population. We define the adverse reaction to Satsuma as Satsuma-induced syndrome
      (SIS). Volunteers were assigned to oral Satsuma challenge in an open manner. The
      results showed that SIS was characterized with symptoms affecting the throat,
      oral cavity, face, gastrointestinal system and eye either individually or in
      combination. A comparative proteomic study was performed to investigate the
      differences of serum proteins in the Post-SC (after Satsuma challenge) and Pre-SC
      (before Satsuma challenge) serum samples of 15 volunteers with severe SIS. Ten
      proteins were identified to be differentially expressed (P<0.05). Of these,
      levels of complement component C9 precursor were elevated significantly in the
      Post-SC serum samples and were further verified by enzyme-linked immunosorbent
      assay, indicating that the complement system may be activated and plays a
      significant role in inflammatory response. Meanwhile, serum samples were
      subjected to immobilized metal affinity capture (IMAC3) protein chip surfaces and
      tested by surface-enhanced laser desorption/ionization-time of flight-mass
      spectrometry. The data were analyzed by Ciphergen ProteinChip Software. A
      diagnostic model was constructed to discriminate the SIS from normal samples,
      using principal component analysis. A total of 50 detected biomarkers were found
      to be different with statistical significance (P<0.05). The multivariate logistic
      analysis demonstrates a complete distinction between the two groups. Our findings
      suggest that these assays may provide potential biomarkers for the diagnosis of
      SIS.

PMID- 28454969
TI  - Pre-drying and submerged cap winemaking: Effects on polyphenolic compounds and
      sensory descriptors. Part I: BRS Rubea and BRS Cora.
AB  - In contrast to the most worldwide used grape varieties, wine production in Brazil
      is mainly devoted to the elaboration of table wines from American grapes and
      hybrids. These grapes show initial disadvantages such as low soluble solids
      content in their optimal stage of ripening and poor color quality. Based on this,
      the Brazilian Agency EMBRAPA Grape and Wine has developed BRS type cultivars in
      order to enhance the quality of the table wines. This study analyzed the phenolic
      composition and sensory profile of BRS Rubea and BRS Cora red wines elaborated by
      traditional and two alternative winemaking technologies: grape pre-drying and
      submerged cap of chaptalized musts. Pre-dried wines presented low concentrations
      of anthocyanins/pyranoanthocyanins and flavonols, suggesting that they were
      partially degraded by the thermal treatment (60 degrees C). These wines were
      described as bitter and full-bodied because of their higher flavan-3-ols content,
      suggesting that these compounds were not greatly influenced by thermal
      degradation. Submerged cap was described as persistent to the palate and with an
      intense violet hue due to its high anthocyanin and flavonol concentrations. The
      antioxidant capacity presented a weak relationship with the anthocyanins and
      stilbenes, but was intensely related to the % of galloylated flavan-3-ols.

PMID- 28454970
TI  - Corrigendum to "Mare's and cow's milk: Promote similar metabolic effects and
      expression of innate markers in Caco-2 cells?" [Food Res. Int. 72 (2015) 184
      190].

PMID- 28454971
TI  - Chemical composition, digestibility and emulsification properties of octenyl
      succinic esters of various starches.
AB  - Octenyl succinate starches are commonly used as emulsifiers and texturizing
      agents in many food-systems. Rice, tapioca, corn, wheat and potato starches were
      modified with octenyl succinic anhydride (OSA) at 3% level. Structural
      characterization, molecular weight, starch digestibility and physical properties
      of starch granule stabilized emulsions were studied for modified starches.
      Modified potato (0.022) and wheat (0.018) starches had the highest and lowest
      degrees of OSA substitution, respectively. For all starches, amylose and
      amylopectin molecular mass was significantly (P<0.05) lower for OSA starches. OSA
      modification may have hydrolyzed the small amylose and amylopectin chains, or
      caused rearrangement of the starch molecules. Although the starch modification
      improved emulsification properties, botanical source showed more influence on
      this parameter. Overall, botanical source had more influence on functional
      properties than degree of substitution. Further studies on OSA group distribution
      and fine molecular structure of amylopectin and relationship with functional
      properties will be important.

PMID- 28454972
TI  - Ameliorating effects of ethyl acetate fraction from onion (Allium cepa L.) flesh
      and peel in mice following trimethyltin-induced learning and memory impairment.
AB  - The anti-amnesic effects of onion (Allium cepa L.) flesh (OF)1 and peel (OP)2 on
      trimethyltin (TMT)3-induced learning and memory dysfunction were investigated to
      confirm learning and memory function. The inhibitory effect against cellular
      acetylcholinesterase (AChE)4 showed that the EtOAc fraction of OP (EOP5, IC50
      value=37.11MUg/mL) was higher than the EtOAc fraction of OF (EOF6, IC50
      value=433.34MUg/mL). The cognitive effects in ICR mice were also evaluated using
      Y-maze, passive avoidance, and Morris water maze tests. After the behavioral
      tests, AChE activity (control=100%, TMT=128%, EOF 20=108%, EOP 10=104%, and EOP
      20=98%), superoxide dismutase (SOD)7 activity, oxidized glutathione (GSSG)8/total
      glutathione (GSH)9 and malondialdehyde (MDA)10 production were examined. These
      results indicate that both EOF and EOP improved learning and memory function. The
      main compounds of the EOF and EOP were analyzed by Q-TOF UPLC/MS, and the results
      were as follows: The EOF (quercetin and quercetin-4'-glucoside) and the EOP
      (quercetin-4'-glucoside and isorhamnetin-4'-glucoside). Consequently, our results
      suggest that both EOF and EOP could be efficacious in improving cognitive
      function through AChE inhibition and antioxidant activity in mice brains.

PMID- 28454973
TI  - Olive paste as vehicle for delivery of potential probiotic Lactobacillus
      plantarum 33.
AB  - Use of probiotic bacteria and consumes in large - in novel foods to provide
      beneficial health effects has attracted an increasing interest by the food
      industry and fermented olives are an excellent example of a new generation of
      those foods from plant origin so as to assure maximum viability by the time of
      ingestion during processing and storage of food products, as well as during
      transit through the gastrointestinal tract. Our study focused on production,
      characterization and assessment of efficacy of microencapsulation upon survival
      of probiotic strains and sensory properties of the final olive paste throughout
      refrigerated storage. Microencapsulation appears to be an effective technique for
      strain survival, depending on the operating temperature and experimental results
      on tolerance to gastrointestinal-like conditions, and ability to adhere to
      intestinal epithelium is thereby presented and discussed. The sensory panel rated
      all experienced matrices as good, including overall acceptance without
      significant preference between them. However, the success of microencapsulation
      was more limited when incorporated into olive paste. Free cells of Lactobacillus
      plantarum 33 proved able to survive in olive paste during storage at refrigerated
      temperatures.

PMID- 28454974
TI  - Influence of lipid type on gastrointestinal fate of oil-in-water emulsions: In
      vitro digestion study.
AB  - The potential gastrointestinal fate of oil-in-water emulsions containing lipid
      phases from different sources was examined: vegetable oils (corn, olive,
      sunflower, and canola oil); marine oils (fish and krill oil); flavor oils (orange
      and lemon oil); and, medium chain triglycerides (MCT). The lowest rates and
      extents of lipid digestion were observed for emulsified flavor oil, followed by
      emulsified krill oil. There was no appreciable difference between the final
      amounts of free fatty acids released for emulsified digestible oils. Differences
      in the digestibility of emulsions prepared using different oils were attributed
      to differences in their compositions, e.g., fatty acid chain length and
      unsaturation. The particle size distribution, particle charge, microstructure,
      and macroscopic appearance of the emulsions during passage through the simulated
      GIT depended on oil type. The results of this study may facilitate the design of
      functional foods that control the digestion and absorption of triglycerides, as
      well as the bioaccessibility of hydrophobic bioactives.

PMID- 28454975
TI  - Kinetics of migration of colloidal particles in meat muscles in the absence and
      presence of a proteolytic enzyme to simulate non-motile bacteria penetration.
AB  - In this study, migration rate and spatial distribution of colloidal particles
      with and without proteolytic enzymes were studied after injection in pork loin
      muscle cubes for 5days at 25 degrees C to simulate behavior of non-motile
      bacteria. Samples were monitored daily by light microscopy and confocal laser
      scanning microscopy and particle distribution and movement analyzed by image
      analysis (MATLAB(r)). The extent of proteolytic activity was assessed by
      determining the tyrosine content in muscle tissue. Results showed that particles
      diffused from the injection hot spot into the inner structure of the meat (1.35+/
      0.99*10-12 to 2.39+/-2.02*10-12m2/s). Upon addition of protease, the migration
      rate increased, i.e. the particle distribution became more widespread due to
      proteolysis of meat proteins reducing resistance to mass transfer. Results
      indicate that particles are able to diffuse into the densely packed fiber
      structure of meat muscles, which is contrary to the long held belief that such
      penetration may not occur in the absence of extensive proteolysis or mechanical
      damage of tissue.

PMID- 28454976
TI  - Impact of the industrial freezing process on selected vegetables -Part II. Colour
      and bioactive compounds.
AB  - In the present study, the impact of the different steps (i.e. blanching,
      freezing, storage following the industrial freezing process and the final cooking
      prior to consumption) of the industrial freezing process was evaluated on colour,
      chlorophylls, lutein, polyphenols and ascorbic acid content of asparagus, green
      beans and zucchini. In addition, the domestic boiling of raw samples was compared
      with the boiling of frozen storage vegetables. Results showed that the blanching
      treatment retained phytochemicals in all studied green vegetables and the frozen
      storage up to 2months did not negatively affected phytochemicals, in particular
      lutein and flavonoids in almost all samples. On the contrary, colour
      significantly changed during blanching and frozen storage. The changes of b*
      (yellowness) and the shift of H degrees  (hue angle) were not coherent with the
      increase of pheophytin. In addition, the greenness (-a*) was found to increase
      with the exception of boiled samples in all vegetables. Generally, in boiled
      frozen vegetables there was a better or comparable retention of bioactive
      compounds with respect to raw ones, and this was especially true for green beans
      and zucchini. Colour changes after cooking did not exhibit the same trends among
      vegetables, being more remarkable for frozen asparagus in comparison with those
      boiled from raw, but overall comparable for green beans and zucchini. In
      conclusion, the overall results of the present study suggest that, when the
      industrial freezing process is well performed, the boiled frozen vegetables do
      not have a lower nutritional value than the fresh ones.

PMID- 28454977
TI  - Curcumin encapsulated in the complex of lysozyme/carboxymethylcellulose and
      implications for the antioxidant activity of curcumin.
AB  - A facile approach was investigated to encapsulate and protect curcumin (Cur) by
      self-assembly of lysozyme (Ly) and carboxymethylcellulose (CMC) of different
      degrees of substitution (DSs). This work studied the influence of Ly-CMC
      coacervates on the binding, solubility and stability of Cur. The interactions of
      Cur with Ly-CMC coacervates were researched by UV-vis, steady-state fluorescence,
      synchronous fluorescence and circular dichroism spectra. These results were
      explained in terms of the formation of Ly-CMC coacervates with electrostatic
      interaction, which led to unfold the structure of Ly for providing Cur with more
      hydrophobic microenvironment than free Ly. Meanwhile, the CMC of higher DS
      provide more negative charges, and produce more attraction to Ly than that of
      lower DS values. Moreover, the coacervates of Ly-CMC of higher DS are found to be
      superior for enhancing the stability of Cur. Our work provided a new insight for
      understanding the biomolecule protective system based on protein/polysaccharide
      complexes.

PMID- 28454978
TI  - Health decentralization at a dead-end: towards new recovery plans for Italian
      hospitals.
AB  - The recent introduction by the central government of recovery plans (RPs) for
      Italian hospitals provides useful insights into the recentralization tendencies
      that are being experienced within the country's decentralized, regional health
      system. The measure also contributes evidence to the debate on whether there is a
      long-term structural shift in national health strategy towards more centralized
      stewardship. The hospital RPs aim to improve the clinical, financial and
      managerial performance of public-hospitals, teaching-hospitals and research
      hospitals through monitoring trends in individual hospitals' expenditure and
      tackling improvements in clinical care. As such they represent the central
      governments recognition of the weaknesses of the decentralization process in the
      health sector. The opponents of the reform argue that financial stability will be
      restored mainly through across-the-board reductions in hospital expenditure,
      personnel layoffs and closing of wards, with considerable negative effects on the
      most vulnerable groups of patients. While hospital RPs are comprehensive and
      complex, unresolved issues remain as to whether hospitals have the necessary
      managerial skills for the development of effective and achievable plans. Without
      also devising an overall plan to tackle the long-standing managerial weaknesses
      of public hospitals, the objectives of the hospital RPs will be undermined and
      the decentralization process in the health system will gradually reach a dead
      end.

PMID- 28454979
TI  - Lutein and its oxidized forms in eye structures throughout prenatal human
      development.
AB  - The presence of carotenoids in the vitreous body, retina, lens, retinal pigment
      epithelium together with choroid (hereinafter RPE), and ciliary body and iris
      together with choroidal stroma (hereinafter CBI) was studied throughout the
      second trimester of prenatal development of the human eye. It has been found that
      the vitreous body, retina, and RPE contain lutein and its oxidized forms.
      Zeaxanthin was not found in the tissues studied. The presence of lutein in the
      vitreous body is transient and no longer detected after 28 weeks of gestation.
      Lutein was not detected in the lens and CBI, but its oxidized forms were found.
      The presence of carotenoids in different tissues of the eye in the course of
      normal eye development and the antioxidant role of carotenoids are discussed.

PMID- 28454980
TI  - Are the results of intravenous thrombolysis trials reproduced in clinical
      practice? Comparison of observed and expected outcomes with the stroke
      thrombolytic predictive instrument (STPI).
AB  - AIM: In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue
      plasminogen activator (rt-PA) increases survival without handicap or dependency
      despite an increased risk of bleeding. This study evaluated whether the results
      of randomized controlled trials are reproduced in clinical practice. METHOD: Data
      from a registry of consecutive patients treated by rt-PA at Lille University
      Hospital were retrospectively analyzed for outcomes, using modified Rankin Scale
      (mRS) scores, at 3 months. The observed outcomes were then compared with the
      probability of good (mRS 0-1) and of catastrophic (mRS 5-6) outcomes, as
      predicted by the stroke-thrombolytic predictive instrument (STPI). RESULTS: Of
      the 1000 consecutive patients (469 male, median age 74 years, median baseline
      National Institutes of Health Stroke Scale 11, median onset-to-needle time
      143min), 438 (43.8%) had a good outcome, 565 (56.5%) had an mRS score 0-2 or
      similar to their pre-stroke mRS, 155 (15.5%) died within 3 months and 74 (7.4%)
      developed symptomatic intracerebral hemorrhage according to ECASS-II (Second
      European-Australasian Acute Stroke Study) criteria. Of the 613 patients (61.3%)
      eligible for evaluation by the s-TPI, the observed rate of good outcomes was
      41.3% (95% CI: 37.5-45.3%), while expected rates with and without rt-PA were
      48.8% (95% CI: 44.8-52.7%) and 32.5% (95% CI: 28.8-36.2%), respectively; the
      observed rate of catastrophic outcomes was 17.0% (95% CI: 14.0-19.9%), while the
      expected rate was 19.2% (95% CI: 16.1-22.4%) with or without rt-PA. CONCLUSION:
      In clinical practice, the rate of good outcomes is slightly lower than expected,
      according to the s-TPI, except for the most severe cases, whereas the rate of
      catastrophic outcomes is roughly similar. However, the rate of good outcomes is
      higher than predicted without treatment. This finding suggests that rt-PA is
      effective for improving outcomes in clinical practice.

PMID- 28454981
TI  - Neuropharmacological characterization of the new psychoactive substance
      methoxetamine.
AB  - The use of new psychoactive substances (NPS) is steadily increasing. One commonly
      used NPS is methoxetamine (MXE), a ketamine analogue. Several adverse effects
      have been reported following MXE exposure, while only limited data are available
      on its neuropharmacological modes of action. We investigated the effects of MXE
      and ketamine on several endpoints using multiple in vitro models. These included
      rat primary cortical cells, human SH-SY5Y cells, human induced pluripotent stem
      cell (hiPSC)-derived iCell(r) Neurons, DopaNeurons and astrocyte co-cultures, and
      human embryonic kidney (HEK293) cells. We investigated effects on several
      neurotransmitter receptors using single cell intracellular calcium [Ca2+]i
      imaging, effects on neuronal activity using micro-electrode array (MEA)
      recordings and effects on human monoamine transporters using a fluorescence-based
      plate reader assay. In rat primary cortical cells, 10 MUM MXE increased the
      glutamate-evoked increase in [Ca2+]i, whereas 10 MUM ketamine was without effect.
      MXE and ketamine did not affect voltage-gated calcium channels (VGCCs), but
      inhibited spontaneous neuronal activity (IC50 0.5 MUM and 1.2 MUM respectively).
      In human SH-SY5Y cells, 10 MUM MXE slightly inhibited the K+- and acetylcholine
      evoked increase in [Ca2+]i. In hiPSC-derived iCell(r)(Dopa)Neurons, only the ATP
      evoked increase in [Ca2+]i was slightly reduced. Additionally, MXE inhibited
      spontaneous neuronal activity (IC50 between 10 and 100 MUM). Finally, MXE
      potently inhibits uptake via monoamine transporters (DAT, NET and SERT), with
      IC50 values in the low micromolar range (33, 20, 2 MUM respectively). Our
      combined in vitro data provide an urgently needed first insight into the multiple
      modes of action of MXE. The use of different models and different (neuronal)
      endpoints can be complementary in pharmacological profiling. Rapid in vitro
      screening methods as those presented here, could be of utmost importance for
      gaining a first mechanistic insight to aid the risk assessment of emerging NPS.

PMID- 28454982
TI  - Dopamine transporter (DAT) genetic hypofunction in mice produces alterations
      consistent with ADHD but not schizophrenia or bipolar disorder.
AB  - ADHD, schizophrenia and bipolar disorder are psychiatric diseases with a strong
      genetic component which share dopaminergic alterations. Dopamine transporter
      (DAT) genetics might be potentially implicated in all these disorders. However,
      in contrast to DAT absence, the effects of DAT hypofunction especially in
      developmental trajectories have been scarcely addressed. Thus, we comprehensively
      studied DAT hypofunctional mice (DAT+/-) from adolescence to adulthood to
      disentangle DAT-dependent alterations in the development of psychiatric-relevant
      phenotypes. From pre-adolescence onward, DAT+/- displayed a hyperactive
      phenotype, while responses to external stimuli and sensorimotor gating abilities
      were unaltered. General cognitive impairments in adolescent DAT+/- were partially
      ameliorated during adulthood in males but not in females. Despite this,
      attentional and impulsivity deficits were evident in DAT+/- adult males. At the
      molecular level, DAT+/- mice showed a reduced expression of Homer1a in the
      prefrontal cortex, while other brain regions as well as Arc and Homer1b
      expression were mostly unaffected. Amphetamine treatments reverted DAT+/-
      hyperactivity and rescued cognitive deficits. Moreover, amphetamine shifted DAT
      dependent Homer1a altered expression from prefrontal cortex to striatal regions.
      These behavioral and molecular phenotypes indicate that a genetic-driven DAT
      hypofunction alters neurodevelopmental trajectories consistent with ADHD, but not
      with schizophrenia and bipolar disorders.

PMID- 28454984
TI  - Cannabidiol Treatment for Refractory Seizures in Sturge-Weber Syndrome.
AB  - BACKGROUND: Sturge-Weber syndrome results in leptomeningeal vascular
      malformations, medically refractory epilepsy, stroke(s), and cognitive
      impairments. Cannabidiol, a cannabinoid without psychoactive properties, has been
      demonstrated in preclinical models to possibly have anticonvulsant, antioxidant,
      and neuroprotective actions. METHODS: Five subjects with Sturge-Weber syndrome
      brain involvement and treatment-resistant epilepsy were enrolled. Motor seizure
      frequency, quality of life, and adverse events were recorded from the eighth week
      of the pretreatment period, eight weeks after starting maintenance dose (week
      14), and the most recent visit. RESULTS: Four subjects had data through week 14,
      one of whom initially withdrew for lack of efficacy but because of other benefits
      re-enrolled with a lower dose. Two subjects at week 14 and three subjects with
      bilateral brain involvement had at the last visit a greater than 50% seizure
      reduction, reported an improved quality of life, and remained on cannabidiol 63
      80 weeks after starting the drug. Three subjects reported mild side effects
      considered related to cannabidiol. CONCLUSION: This study suggests that
      cannabidiol may be well tolerated as adjunctive medication for seizure management
      and provides initial data supporting further study of cannabidiol in individuals
      with Sturge-Weber syndrome.

PMID- 28454983
TI  - Emerging pharmacotherapies for alcohol use disorder.
AB  - The identification of different stages within the alcohol use disorder (AUD)
      cycle that are linked to neurocircuitry changes in pathophysiology associated
      with the negative emotional states of abstinence has provided a view of
      medication development for AUD that emphasizes changes in the brain reward and
      stress systems. Alcohol use disorder can be defined as a chronic relapsing
      disorder that involves compulsive alcohol seeking and taking, loss of control
      over alcohol intake, and emergence of a negative emotional state during
      abstinence. The focus of early medications development was to block the
      motivation to seek alcohol in the binge/intoxication stage. More recent work has
      focused on reversing the motivational dysregulations associated with the
      withdrawal/negative affect and preoccupation/anticipation stages during
      protracted abstinence. Advances in our understanding of the neurocircuitry and
      neuropharmacological mechanisms that are involved in the development and
      maintenance of the withdrawal/negative affect stage using validated animal models
      have provided viable targets for future medications. Another major advance has
      been proof-of-concept testing of potential therapeutics and clinical validation
      of relevant pharmacological targets using human laboratory models of protracted
      abstinence. This review focuses on future targets for medication development
      associated with reversal of the loss of reward function and gain in brain stress
      function that drive negative reinforcement in the withdrawal/negative affect
      stage of addiction. Basic research has identified novel neurobiological targets
      associated with the withdrawal/negative affect stage and
      preoccupation/anticipation stage, with a focus on neuroadaptive changes within
      the extended amygdala that account for the transition to dependence and
      vulnerability to relapse. This article is part of the Special Issue entitled
      "Alcoholism".

PMID- 28454985
TI  - Use of a 17-Gene Prognostic Assay in Contemporary Urologic Practice: Results of
      an Interim Analysis in an Observational Cohort.
AB  - OBJECTIVE: To study the impact of genomic testing in shared decision making for
      men with clinically low-risk prostate cancer (PCa). MATERIALS AND METHODS:
      Patients with clinically low-risk PCa were enrolled in a prospective, multi
      institutional study of a validated 17-gene tissue-based reverse transcription
      polymerase chain reaction assay (Genomic Prostate Score [GPS]). In this paper we
      report on outcomes in the first 297 patients enrolled in the study with valid 17
      gene assay results and decision-change data. The primary end points were shared
      decision on initial management and persistence on active surveillance (AS) at 1
      year post diagnosis. AS utilization and persistence were compared with similar
      end points in a group of patients who did not have genomic testing (baseline
      cohort). Secondary end points included perceived utility of the assay and patient
      decisional conflict before and after testing. RESULTS: One-year results were
      available on 258 patients. Shift between initial recommendation and shared
      decision occurred in 23% of patients. Utilization of AS was higher in the GPS
      tested cohort than in the untested baseline cohort (62% vs 40%). The proportion
      of men who selected and persisted on AS at 1 year was 55% and 34% in the GPS and
      baseline cohorts, respectively. Physicians reported that GPS was useful in 90% of
      cases. Mean decisional conflict scores declined in patients after GPS testing.
      CONCLUSION: Patients who received GPS testing were more likely to select and
      persist on AS for initial management compared with a matched baseline group.
      These data indicate that GPS help guide shared decisions in clinically low-risk
      PCa.

PMID- 28454986
TI  - Old Tools, Old Problems, New Solution: The Use of a Modified Cecil-Culp Concept
      in the Trauma Setting.
AB  - A 12-year-old boy sustained a close-range shotgun wound with buckshot to the
      penis and lower abdomen. The proximal two-thirds of the corpora cavernosa was
      obliterated and the distal third was thrombosed. All dorsal penile skin was lost.
      The urethra remained intact. The patient underwent multiple debridements,
      allowing the wound to declare its borders. Employing the tissue transfer concept
      used by Cecil and Culp in hypospadias repairs, the penis was marsupialized onto
      the suprapubic area where it remained for 8 months. After 8 months, the patient
      underwent a graft delaying procedure followed by a graft harvest 2 months later
      and penoplasty tubularization.

PMID- 28454987
TI  - Expanding Immunotherapy Options for Bladder Cancer: Commentary on: Pembrolizumab
      as Second-Line Therapy for Advanced Urothelial Carcinoma.

PMID- 28454988
TI  - Physicians' Perceptions of Factors Influencing the Treatment Decision-making
      Process for Men With Low-risk Prostate Cancer.
AB  - OBJECTIVE: To assess physicians' attitudes regarding multiple factors that may
      influence recommendations for active surveillance (AS) vs active treatment (AT)
      given the central role physicians play in the treatment decision-making process.
      MATERIALS AND METHODS: We conducted semistructured interviews to assess factors
      that physicians consider important when recommending AS vs AT, as well as
      physicians' perceptions of what their patients consider important in the
      decision. Participants included urologists (N = 11), radiation oncologists (N =
      12), and primary care physicians (N = 10) from both integrated and fee-for
      service healthcare settings. RESULTS: Across the specialties, quantitative data
      indicated that most physicians reported that their recommendations for AS were
      influenced by patients' older age, willingness and ability to follow a
      surveillance protocol, anxiety, comorbidities, life expectancy, and treatment
      preferences. Qualitative findings highlighted physicians' concerns about
      malpractice lawsuits, given the possibility of disease progression. Additionally,
      most physicians noted the role of the healthcare setting, suggesting that
      financial incentives may be associated with AT recommendations in fee-for-service
      settings. Finally, most physicians reported spouse or family opposition to AS due
      to their own anxiety or lack of understanding of AS. CONCLUSION: We found that
      patient and physician preferences, healthcare setting, and family or spouse
      factors influence physicians' treatment recommendations for men with low-risk
      PCa. These were consistent themes across physician subspecialties in both an
      Health Maintenance Organization and in fee-for-service settings.

PMID- 28454989
TI  - Differences in male and female subjective experience and physiological reactions
      to emotional stimuli.
AB  - Research based on self-reported data often indicates that women are the more
      emotional sex. The present study examined differences in emotion between the
      sexes across two components of the emotional process: subjective experience and
      physiological reactions to emotional stimuli. During the experimental study,
      participants (N=124; 22.5+/-2.88; 51 males) subjectively rated their emotional
      experience (valence and intensity) towards presented positive and negative
      affective stimuli, while physiological reactions (facial electromyography, heart
      rate, skin conductance, and finger skin temperature) were measured during
      expositions. Results from self-reports suggest that women declared more intensive
      emotional experiences for positive and negative stimuli and rated negative
      stimuli as more negative in comparison to men. Physiological measurements showed
      differences between the sexes in the physiological baseline measurements (facial
      electromyography, skin conductance and finger skin temperature). However,
      physiological responses towards positive or negative emotional stimuli did not
      prove to be different between men and women, except for finger skin temperature.
      Relations between self-reported subjective experiences and physiological changes
      were weak and insignificant. Collectively, our findings suggest certain emotional
      differences experienced between men and women. These differences can be found
      specifically in self-reported subjective experiences, while significant
      differences were not predominantly present in recorded physiological reactions.

PMID- 28454990
TI  - Brain disease, connectivity, plasticity and cognitive therapy: A neurological
      view of mental disorders.
AB  - INTRODUCTION: Our conception of the mind-brain relationship has evolved from the
      traditional idea of dualism to current evidence that mental functions result from
      brain activity. This paradigm shift, combined with recent advances in
      neuroimaging, has led to a novel definition of brain functioning in terms of
      structural and functional connectivity. The purpose of this literature review is
      to describe the relationship between connectivity, brain lesions, cerebral
      plasticity, and functional recovery. DEVELOPMENT: Assuming that brain function
      results from the organisation of the entire brain in networks, brain dysfunction
      would be a consequence of altered brain network connectivity. According to this
      approach, cognitive and behavioural impairment following brain damage result from
      disrupted functional organisation of brain networks. However, the dynamic and
      versatile nature of these circuits makes recovering brain function possible.
      Cerebral plasticity allows for functional reorganisation leading to recovery,
      whether spontaneous or resulting from cognitive therapy, after brain disease.
      CONCLUSIONS: Current knowledge of brain connectivity and cerebral plasticity
      provides new insights into normal brain functioning, the mechanisms of brain
      damage, and functional recovery, which in turn serve as the foundations of
      cognitive therapy.

PMID- 28454991
TI  - Gravity of Intracranial Pressure Shifts in Outer Space.

PMID- 28454992
TI  - Accuracy of VarioGuide Frameless Stereotactic System Against Frame-Based
      Stereotaxy: Prospective, Randomized, Single-Center Study.
AB  - INTRODUCTION: Frameless stereotactic brain biopsy systems are widely used today.
      VarioGuide (VG) is a relatively novel frameless system. Its accuracy was studied
      in a laboratory setting but has not yet been studied in the clinical setting. The
      purpose of this study was to determine its accuracy and diagnostic yield and to
      compare this with frame-based (FB) stereotaxy. MATERIAL AND METHODS: Overall, 53
      patients (33 males and 20 females, 60 +/- 15 years old) were enrolled into this
      prospective, randomized, single-center study. Twenty-six patients were randomized
      into the FB group and 27 patients into the VG group. Real trajectory was pointed
      on intraoperative magnetic resonance. The distance of the targets and angle
      deviation between the planned and real trajectories were computed. The overall
      discomfort of the patient was subjectively assessed by the visual analog scale
      score. RESULTS: The median lesion volume was 5 mL (interquartile range [IQR]: 2
      16 mL) (FB) and 16 mL (IQR: 2-27 mL) (VG), P = 0.133. The mean distance of the
      targets was 2.7 +/- 1.1 mm (FB) and 2.9 +/- 1.3 mm (VG), P = 0.456. Mean angle
      deviation was 2.6 +/- 1.3 deg (FB) and 3.5 +/- 2.1 deg (VG), P = 0.074.
      Diagnostic yield was 93% (25/27) in VG and 96% (25/26) in FB, P = 1.000. Mean
      operating time was 47 +/- 26 minutes (FB) and 59 +/- 31 minutes (VG), P = 0.140.
      One minor bleeding was encountered in the VG group. Overall patient discomfort
      was significantly higher in the FB group (visual analog scale score 2.5 +/- 2.1
      vs. 1.2 +/- 0.6, P = 0,004). CONCLUSIONS: The VG system proved to be comparable
      in terms of the trajectory accuracy, rate of complications and diagnostic yield
      compared with the "gold standard" represented by the traditional FB stereotaxy
      for patients undergoing brain biopsy. VG is also better accepted by patients.

PMID- 28454993
TI  - Frameless Stereotactic Radiosurgery for Treatment of Multiple Sclerosis-Related
      Trigeminal Neuralgia.
AB  - BACKGROUND: Trigeminal neuralgia (TN) affects 7% of patients with multiple
      sclerosis (MS). In such patients, TN is difficult to manage either
      pharmacologically and surgically. Radiosurgical rhizotomy is an effective
      treatment option. The nonisocentric geometry of radiation beams of CyberKnife
      introduces new concepts in the treatment of TN. Its efficacy for MS-related TN
      has not yet been demonstrated. METHODS: Twenty-seven patients with refractory TN
      and MS were treated. A nonisocentric beams distribution was chosen; the maximal
      target dose was 72.5 Gy. The maximal dose to the brainstem was <12 Gy. Effects on
      pain, medications, sensory disturbance, rate, and time of pain recurrence were
      analyzed. RESULTS: Median follow-up was 37 (18-72) months. Barrow Neurological
      Institute pain scale score I-III was achieved in 23/27 patients (85%) within 45
      days. Prescription isodose line (80%) accounting for a dose of 58 Gy incorporated
      an average of 4.85 mm (4-6 mm) of the nerve and mean nerve volume of 26.4 mm3
      (range 20-38 mm3). Seven out of 27 patients (26%) had mild, not bothersome,
      facial numbness (Barrow Neurological Institute numbness score II). The rate of
      pain control decreased progressively after the first year, and only 44% of
      patients retained pain control 4 years later. CONCLUSIONS: Frameless radiosurgery
      can be effectively used to perform retrogasserian rhizotomy. Pain relief was
      satisfactory and, with our dose/volume constraints, no sensory complications were
      recorded. Nonetheless, long-term pain control was possible in less than half of
      the patients. This is a limitation that CyberKnife radiosurgery shares with other
      techniques in MS patients.

PMID- 28454994
TI  - Molecular masquerading of rare EGFR L858M/L861R mutations as common L858R/L861Q
      mutations by PNA clamping assay.

PMID- 28454996
TI  - Reduction Osteotomy of the Prominent Tibial Tubercle After Osgood-Schlatter
      Disease.
AB  - PURPOSE: To evaluate the functional and clinical outcome of a new closing-wedge
      osteotomy for the prominent tibial tubercle after Osgood-Schlatter disease.
      METHODS: Between 2010 and 2014, 7 consecutive adults (mean age, 28.6 years;
      range, 26-35 years) were treated by closing-wedge reduction osteotomy of a
      painful tibial tubercle. All patients had prior nonsurgical and surgical
      treatment. Preoperative and postoperative tubercular prominence, Caton-Deschamps
      index for patellar height, the Kujala Anterior Knee Pain Scale, Lysholm Knee
      Score as well as visual analog scale score and Tegner activity scores were
      recorded. RESULTS: Mean follow-up after reduction osteotomy was 31.3 months (27
      41 months). The bony prominence of the tibial tubercle was significantly reduced
      (mean 8 mm, P < .001) and the Caton-Deschamps index was lowered from 1.29 to 1.09
      (P < .001). From preoperative to last follow-up, the Kujala Anterior Knee Pain
      Scale increased from 54.71 preoperative to 84.71 (P < .001); the Lysholm Knee
      Score improved from 72.42 to 94.14 (P < .001); the Tegner activity score
      increased from 3.1 to 5.7 (P < .001), whereas the visual analog scale
      significantly decreased from 5.8 to 1.2 (P < .001). No complications were
      recorded, and all patients were satisfied with clinical outcome. CONCLUSIONS:
      Closing-wedge osteotomy of the tibial tubercle effectively reduced the bony
      prominence after Osgood-Schlatter disease and consecutively improved the outcome
      in terms of knee pain and function. Thus, we can recommend this procedure in
      selected patients. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 28454995
TI  - A multicenter clinical exome study in unselected cohorts from a consanguineous
      population of Saudi Arabia demonstrated a high diagnostic yield.

PMID- 28454997
TI  - Retrospective Comparative Analysis of Elbow Arthroscopy Used to Treat Primary
      Osteoarthritis With and Without Release of the Posterior Band of the Medial
      Collateral Ligament.
AB  - PURPOSE: To evaluate the clinical and functional outcomes of arthroscopic
      debridement arthroplasty with the release of the posterior band of the medial
      collateral ligament in patients with primary osteoarthritis. METHODS: We
      evaluated 43 patients treated with arthroscopic debridement arthroplasty for
      elbow osteoarthritis from February 2006 to February 2014. In group A (n = 19),
      the posterior band of the medial collateral ligament was released, and in group B
      (n = 24), it was not released. The mean follow-up period in groups A and B was
      55.4 months (range, 24-100 months) and 62.2 months (range, 24-103 months),
      respectively. Clinical results were evaluated by measuring the preoperative and
      postoperative range of motion (ROM) of the elbow, visual analog scale score, and
      Mayo Elbow Performance Score. RESULTS: Both groups showed significant improvement
      in clinical outcome (visual analog scale and Mayo Elbow Performance Score) at the
      final follow-up compared with preoperative evaluation (group A, P = .009 and
      .013, respectively; group B, P = .015 and .008, respectively). Group A showed
      significant improvement in increased flexion at 6 months of follow-up (P = .043).
      However, there was no statistically significant difference in postoperative ROM
      and clinical results between the 2 groups at the final follow-up (P = .482).
      CONCLUSIONS: Arthroscopic debridement arthroplasty with the release of the
      posterior band of the medial collateral ligament was associated with improved
      flexion at the 6-month postoperative follow-up, but no significant difference
      between the groups was observed at the final follow-up. Therefore, the additional
      release of the posterior band of the medial collateral ligament may be
      unnecessary for improving postoperative ROM. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 28454998
TI  - Finite Element Analysis of the Biomechanical Effects of 3 Posterolateral Corner
      Reconstruction Techniques for the Knee Joint.
AB  - PURPOSE: To compare the forces exerted on the cruciate ligaments and the contact
      stresses on the tibiofemoral (TF) and patellofemoral (PF) joints with respect to
      3 different tibial- and fibular-based posterolateral corner (PLC) reconstructions
      under dynamic loading conditions. METHODS: A subject-specific finite element knee
      model was developed by using 3-dimensional anatomic data from motion captures in
      gait and squat activities, including in vivo knee joint kinematics and muscle
      forces for the single subject. Cruciate ligament forces and contact stresses on
      the TF and PF joints under 3 PLC reconstruction techniques (tibial-based, TBR;
      modified fibular-based, mFBR; conventional fibular-based, cFBR) and PLC-deficient
      models were compared with those of the intact model in gait and squat loading
      conditions. RESULTS: The cruciate ligament forces in the 3 surgical models
      differed from those in the intact model. The greatest differences in ligament
      forces from the intact model were found in the cFBR model, whereas there were no
      remarkable differences between the TBR and mFBR models in both gait and squat
      loading conditions. Contact stresses on the lateral TF and PF joints of the 3
      surgical models were greater than those of the intact model under the squat
      loading condition. CONCLUSIONS: The biomechanical effects achieved using the
      anatomic reconstruction technique were found to be improved compared with those
      using nonanatomic reconstruction techniques. However, the ligament forces and
      contact stresses under normal conditions could not be restored through any of the
      3 techniques. CLINICAL RELEVANCE: Anatomic TBR and FBR for grade III PLC injuries
      could restore better biomechanics in the knee joint compared with nonanatomic
      reconstruction. However, discrepancy with the normal condition requires further
      modification of surgical techniques.

PMID- 28454999
TI  - Research Pearls: The Significance of Statistics and Perils of Pooling. Part 1:
      Clinical Versus Statistical Significance.
AB  - Patient-reported outcomes (PROs) are increasingly being used in today's rapidly
      evolving health care environment. The value of care provision emphasizes the
      highest quality of care at the lowest cost. Quality is in the eye of the
      beholder, with different stakeholders prioritizing different components of the
      value equation. At the center of the discussion are the patients and their
      quantification of outcome via PROs. There are hundreds of different PRO
      questionnaires that may ascertain an individual's overall general health, quality
      of life, activity level, or determine a body part-, joint-, or disease-specific
      outcome. As providers and patients increasingly measure outcomes, there exists
      greater potential to identify significant differences across time points due to
      an intervention. In other words, if you compare groups enough, you are bound to
      eventually detect a significant difference. However, the characterization of
      significance is not purely dichotomous, as a statistically significant outcome
      may not be clinically relevant. Statistical significance is the direct result of
      a mathematical equation, irrelevant to the patient experience. In clinical
      research, despite detecting statistically significant pre- and post-treatment
      differences, patients may or may not be able to perceive those differences.
      Thresholds exist to delineate whether those differences are clinically important
      or relevant to patients. PROs are unique, with distinct parameters of clinical
      importance for each outcome score. This review highlights the most common PROs in
      clinical research and discusses the salient pearls and pitfalls. In particular,
      it stresses the difference between statistical and clinical relevance and the
      concepts of minimal clinically important difference and patient acceptable
      symptom state. Researchers and clinicians should consider clinical importance in
      addition to statistical significance when interpreting and reporting
      investigation results.

PMID- 28455000
TI  - Ethylglucuronide in the urine as a marker of alcohol consumption during
      pregnancy: Comparison with four alcohol screening questionnaires.
AB  - Ethyl glucuronide (EtG) is an ethanol metabolite and EtG is used as a biomarker
      of alcohol drinking. EtG can be detected in the blood and in several biological
      matrices including urine, hair and nails. Alcohol consumption during pregnancy is
      a strong risk factor for fetus health so in the recent years different strategies
      to reveal alcohol use have been planning including the use of screening
      questionnaires as the AUDIT-C, T-ACE and TWEAK. The present study aims to
      investigate in pregnant women the specificity and predictive value of the AUDIT
      C, T-ACE and TWEAK plus a food diary in use in Sapienza University Hospital
      compared with the results of urine EtG measurement. Seventy pregnant women were
      enrolled and examined. Urine samples were provided by pregnant women immediately
      after the interviews. EtG determinations were performed by Enzyme Immunoassay
      with a cut-off established at 100ng/mL. Data show that 34.28% of the enrolled
      pregnant women overcame the EtG cut off. No direct correlation was found between
      EtG data and the alcohol screening interviews showing lower levels of alcohol
      consumption, although T-ACE revealed the same at risk percentage. However, a
      significant concordance was observed with food diary data and T-ACE only in
      patients with higher EtG urinary concentration. This study provides clinical
      evidence that the diagnosis of maternal alcohol consumption during pregnancy only
      based on indirect methods, such as questionnaires and food diary, may
      significantly underestimate alcohol use.

PMID- 28455001
TI  - The influence of AICAR - direct activator of AMP-activated protein kinase (AMPK) 
      on liver proteome in apoE-knockout mice.
AB  - There is a growing body of evidence that altered functioning of apoE may
      aggravate cellular energy homeostasis and stress response, leading to oxidative
      stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress and
      inflammation, leading to hypercholesterolemia, dyslipidemia, liver steatosis and
      neurodegeneration. One of the key cellular responses to mitochondria and ER
      stress related processes and cellular energy imbalance is AMP-activated protein
      kinase (AMPK), considered as a cellular master energy sensor and critical
      regulator of mitochondrial homeostasis. The aim of our study was to use
      differential proteomics and transcriptomics approach to elucidate the effect of
      direct AMPK activator AICAR on liver proteome in apoE-/- mice - experimental
      model of atherosclerosis and moderate nonalcoholic steatosis. We applied Isobaric
      Tags for Relative and Absolute Quantitation (iTRAQ) labeling and two-dimensional
      chromatography coupled with mass spectrometry (2DLC-MS/MS) MudPIT strategy, as
      well as RT-PCR to investigate the changes in mitochondrial and cytosolic proteins
      and transcripts expression in 6-month old AICAR-treated apoE-/-. AICAR elicited
      induction of proteins related to mitochondrial beta-oxidation, protein
      degradation and energy producing pathways (i.a. tricarboxylic acid cycle members
      and mitochondrial adenylate kinase 2). On the other hand, AICAR repressed
      inflammatory and pro-apoptotic markers in the apoE-/- mice liver, alongside
      reduction in several peroxisomal proteins, possibly suggesting induction of anti
      oxidative pexophagy.

PMID- 28455002
TI  - Treatment schedule and estrogen receptor-status influence acquisition of
      doxorubicin resistance in breast cancer cells.
AB  - Breast cancer is the most common cancer in women for which doxorubicin is still
      the mainstay treatment. However, chemotherapy resistance is a major limitation in
      breast cancer treatment. Role of treatment schedule and estrogen receptor (ER)
      status in subtypes of breast cancers in acquired resistance development is not
      clear. Therefore, objective of this study was to evaluate whether the treatment
      schedule and ER status in breast cancer cells influence the doxorubicin
      resistance. To address these questions, ER-positive MCF-7 and triple-negative MDA
      MB-231 breast cancer cell lines were given either continuous or intermittent
      exposure with clinically relevant concentration of doxorubicin and the influence
      of these two treatment strategies on resistance to drug sensitivity was
      evaluated. Results revealed that intermittent treatment but not the continuous
      treatment induced resistance in breast cancer cells against doxorubicin. MCF-7
      cells developed relatively earlier and high level of resistance when compared to
      MDA-MB-231 cells. Acquisition of epithelial to mesenchymal transition (EMT) and
      cancer stem cell-like phenotype was also observed during resistance development
      in MCF-7 cells. Changes in the expression of selected marker genes including drug
      transporters confirmed doxorubicin resistance in these cells. In summary, this
      study suggests that acquisition of resistance against doxorubicin depends on the
      treatment schedule of this drug as well as the estrogen receptor-based subtypes
      of breast cancer. Additionally, acquisition of EMT and stem cell-like phenotype
      further provided a molecular basis for breast cancer subtype-dependent
      chemotherapeutic resistance development. Findings of this study will have
      significant clinical implications in optimizing the chemotherapy schedule to
      minimize chemoresistance in breast cancer patients.

PMID- 28455003
TI  - Simultaneous head and facial computed tomography scans for assessing facial
      fractures in patients with traumatic brain injury.
AB  - INTRODUCTION: Patients with traumatic brain injury (TBI) may have concomitant
      facial fractures. While most head injury patients receive head computed
      tomography (CT) scans for initial evaluation, the objective of our study was to
      investigate the value of simultaneous facial CT scans in assessing facial
      fractures in patients with TBI. METHODS: From January 1, 2015 to December 31,
      2015, 1649 consecutive patients presenting to our emergency department (ED) with
      a TBI who received CT scans using the protocol for head and facial bones were
      enrolled. The clinical data and CT images were reviewed via a standardized
      format. RESULTS: In our cohort, 200 patients (12.1%) had at least one facial
      fracture shown on the CT scans. Patients with facial fractures were more likely
      to have initial loss of consciousness (ILOC; p<0.001), a Glasgow coma scale of 8
      or less (p<0.001), moderate or severe degrees of head injury severity scale
      (p<0.001), positive physical examination findings (p<0.001), and positive CT
      cranial abnormalities (p<0.001). A total of 166 (83.0%) patients with facial
      fractures required further facial CT scans instead of conventional head CT scans
      alone. Surgical intervention was mandatory in 73 (44.0%) of the 166 patients, who
      more frequently exhibited fractures of the lower third of the face (p<0.001) and
      orbital fractures (p=0.019). CONCLUSIONS: TBI patients with risk factors may have
      a higher probability of concomitant facial fractures. Fractures of the lower
      third of the face and orbit are easily overlooked in routine head CT scans but
      often require surgical intervention. Therefore, simultaneous head and facial CT
      scans are suggested in selected TBI patients.

PMID- 28455004
TI  - Editor's perspective on the 4th edition of the WHO head and neck tumor
      classification.

PMID- 28455005
TI  - Outcomes of Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid
      Leukemia Patients with Abnormalities of the Short Arm of Chromosome 17.
AB  - We retrospectively analyzed a Japanese nationwide database to elucidate the
      impact of abnormalities in the short arm of chromosome 17 (abnl[17p]) on the
      outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in
      patients with acute myeloid leukemia. Of 10,923 patients, 262 (2.4%) had
      abnl(17p), 235 of whom were classified into the poor cytogenetic risk group
      according to the National Comprehensive Cancer Network criteria. The median
      follow-up period was 1425 days. In abnl(17p) versus non-abnl(17p) patients of
      poor cytogenetic risk group, overall survival (OS), disease-free survival,
      cumulative incidence of disease relapse, and nonrelapse mortality rates at 5
      years after allo-HSCT were 9.2% versus 27.4%, 7.8% versus 25.0%, 66.6% versus
      49.4%, and 25.6% versus 25.6%, respectively. In contrast to the other types of
      abnl(17p), isochromosome 17q rarely encompassed the poor cytogenetic risk traits
      and did not adversely affect OS. Among the abnl(17p) patients, male sex,
      nonremission disease status at transplantation, and poor cytogenetic risk group
      were significantly associated with shorter OS. In conclusion, the presence of an
      abnl(17p) negatively affects allo-HSCT outcomes, which are influenced by the type
      of abnormality. Prompt initiation of allo-HSCT during complete remission may
      improve outcomes.

PMID- 28455007
TI  - 5alpha-reductase inhibitors and depression.

PMID- 28455006
TI  - Association of Plasma CD163 Concentration with De Novo-Onset Chronic Graft-versus
      Host Disease.
AB  - Chronic graft-versus-host disease (GVHD) is the leading cause of long-term
      morbidity and mortality after allogeneic hematopoietic cell transplantation. To
      identify prognostic plasma proteins associated with de novo- or quiescent-onset
      chronic GVHD (cGVHD), we performed a discovery and validation proteomic study.
      The total study cohort included 167 consecutive patients who had no clinical
      evidence of GVHD under minimum glucocorticoid administration and had available
      plasma samples obtained at 80 +/- 14 days after transplantation. We first used
      high-throughput mass spectrometry to screen pooled plasma using 20 cases with
      subsequent cGVHD and 20 controls without it, and we identified 20 candidate
      proteins. We then measured 12 of the 20 candidate proteins by ELISA on the same
      individual samples and identified 4 proteins for further verification (LGALS3BP,
      CD5L, CD163, and TXN for de novo onset, and LGALS3BP and CD5L for quiescent
      onset). The verification cohort included 127 remaining patients. The cumulative
      incidence of de novo-onset cGVHD was higher in patients with higher plasma
      soluble CD163 concentrations at day 80 than those with lower concentrations (75%
      versus 40%, P = .018). The cumulative incidence of de novo- or quiescent-onset
      cGVHD did not differ statistically according to concentrations of the 3 other
      proteins at day 80. CD163 is a macrophage scavenger receptor and is elevated in
      oxidative conditions. These results suggest that monocyte or macrophage
      activation or increased oxidative stress may contribute to the pathogenesis of
      cGVHD.

PMID- 28455008
TI  - An unusual case of an angioplasty wire entrapped and fractured within the struts
      of a recently implanted coronary stent: Treatment with the implantation of a
      "jailing" stent.

PMID- 28455009
TI  - Influence of heating treatment and membrane concentration on the formation of
      soluble aggregates.
AB  - This study investigated the effect of thermal denaturation on milk concentrated
      by ultrafiltration (UF) with or without diafiltration (DF) at various time
      temperature combinations. The non-sedimentable protein fractions present in milk
      after heating were analyzed using size exclusion chromatography and their
      composition was determined. The extent of whey protein denaturation and the
      composition of the soluble complexes depended not only on heating temperature and
      time, but also on the protein concentration. There was a greater extent of
      protein aggregation in concentrated milk compared to 1* milk, and there was a
      significant difference in the size and composition of the aggregates present in
      the non-sedimentable fraction depending on whether the milk was concentrated only
      by UF or if DF was also used. DF milk contained a higher concentration of non
      sedimentable protein compared to UF milk. In all samples, kappa-casein and beta
      lactoglobulin were the main proteins present in the soluble aggregates, but
      higher temperatures and longer heating times resulted in greater extents of
      denaturation of alpha-lactalbumin. This work clearly identified differences in
      the extent of aggregation between milk concentrated by UF or UF and DF, and
      unconcentrated milk, with important consequences on the processing functionality
      of caseins.

PMID- 28455010
TI  - Impact of information and in-home sensory exposure on liking and willingness to
      pay: The beginning of Fairtrade labeled coffee in France.
AB  - This study was conducted to assess how the Fairtrade label interacts with the
      perception of intrinsic product characteristics on liking and purchase decisions
      and to estimate the evolution of this interaction after exposure to coffees
      and/or exposure to ethical information. In the first session, 119 consumers gave
      liking scores for 2 regular and 2 Fairtrade coffees under a blind tasting
      condition. Then, they were asked to indicate the maximum price they would pay for
      each product in 2 auctions taking place under different information conditions.
      In the first auction, participants saw the packaging but did not taste the
      coffee; in the second auction, they could both taste the coffee and see the
      packaging. After the first session, the consumers were randomly split into 4
      groups, and these groups were exposed for one month to different conditions
      before returning to the lab for exactly the same measurements as in the first
      session. The first of the 4 groups was not exposed to sensory characteristics or
      ethical information. Each consumer of the second group was only exposed to
      sensory characteristics of the coffees (one packet of his/her least liked regular
      and ethical coffees delivered in blind packaging for home consumption). The third
      group was exposed to sensory characteristics and ethical information (the same as
      the second group but using the original coffee packaging showing fair trade
      information). The final group was only exposed to ethical information. Results
      showed that the hedonic scores of the least liked ethical and regular products
      increased from sessions 1 to 2, but not significantly more when consumers were
      exposed to these products between the sessions. However, while consumers offered
      lower prices for ethical products at the first session, those who were exposed to
      ethical information increased their willingness to pay for ethical products. This
      effect became statistically significant when consumers could taste the products
      before making their bid. The effect of exposure to ethical information was also
      transferred to the willingness to pay for the ethical product to which the
      consumers were not exposed. This study highlights the interest of a design, which
      makes it possible to assess the impact over time of sensory and external
      information on the willingness to pay.

PMID- 28455011
TI  - Use of Schizosaccharomyces pombe and Torulaspora delbrueckii strains in mixed and
      sequential fermentations to improve red wine sensory quality.
AB  - One of the main opportunities in the use of non-Saccharomyces yeasts is its great
      intraspecific variability in relation to the synthesis of secondary products of
      fermentation. Thus, mixed or sequential fermentation with non-Saccharomyces can
      increase the synthesis of certain metabolites that are important for colour
      stability, such as acetaldehyde and pyruvic acid (vitisin precursors) or
      vinylphenols (vinylphenolic pyranoanthocyanin precursors). Furthermore, the
      selection and use of non-Saccharomyces yeast strains with good yields in the
      production of certain volatile compounds (ethyl lactate, 2,3-butanediol, 2
      phenylethyl acetate), with limited formation of higher alcohols, is a way to
      improve the aromatic profile of red wine. The main aim of this work was to
      evaluate the influence of sequential and mixed fermentations with
      Schizosaccharomyces pombe and Torulaspora delbrueckii strains on red wine's
      sensory quality. Anthocyanins and aromatic profiles, as well as glycerol and
      organic acid content, were analysed in the red wines obtained. Results show that,
      in general, mixed fermentations can promote an increment in polyols synthesis,
      while sequential fermentations can enhance the herbaceous aroma. Moreover, the
      use of T. delbrueckii in mixed fermentations allowed an increase to the fruity
      character of red wine. The use of S. pombe in sequential fermentations increased
      the stability of the colouring matter by favouring vitisins and vinylphenolic
      pyranoanthocyanin formation.

PMID- 28455012
TI  - 1H NMR based metabolic profiling of eleven Algerian aromatic plants and
      evaluation of their antioxidant and cytotoxic properties.
AB  - Eleven Algerian medicinal and aromatic plants (Aloysia triphylla, Apium
      graveolens, Coriandrum sativum, Laurus nobilis, Lavandula officinalis, Marrubium
      vulgare, Mentha spicata, Inula viscosa, Petroselinum crispum, Salvia officinalis,
      and Thymus vulgaris) were selected and their hydroalcoholic extracts were
      screened for their antiradical and antioxidant properties in cell-free systems.
      In order to identify the main metabolites constituting the extracts, 1H NMR-based
      metabolic profiling was applied. Data obtained emphasized the antiradical
      properties of T. vulgaris, M. spicata and L. nobilis extracts (RACI 1.37, 0.97
      and 0.93, respectively), whereas parsley was the less active as antioxidant (RACI
      -1.26). When the cytotoxic effects of low and antioxidant doses of each extract
      were evaluated towards SK-N-BE(2)C neuronal and HepG2 hepatic cell lines, it was
      observed that all the extracts weakly affected the metabolic redox activity of
      the tested cell lines. Overall, data strongly plead in favor of the use of these
      plants as potential food additives in replacement of synthetic compounds.

PMID- 28455013
TI  - Inactivation of murine norovirus-1 and hepatitis A virus on fresh meats by
      atmospheric pressure plasma jets.
AB  - In the current study, inactivation effect of atmospheric pressure plasma (APP)
      jets (10s-20min) was investigated against murine norovirus (MNV-1), as a
      norovirus (NoV) surrogate and hepatitis A virus (HAV) associated with three types
      of fresh meats (beef loin, pork shoulder and chicken breast). The quality
      characteristics of fresh meats, such as surface color, moisture content and
      thiobarbituric acid reactive substance (TBARS) were also examined. After 5-20min
      of treatment with APP jets, the reduction in MNV-1 titers (initial inoculums of
      107 plaque-forming units (PFU)) were >2log10PFU/mL in the three types of meat.
      After 5-20min treatment with APP jets, the reduction in HAV titers (initial
      inoculums of 106PFU) were >1log10PFU/mL in the three types of meat. There was no
      significant difference (p>0.05) in the L*, a*, and b* values for APP jet
      treatment times below 5min. Furthermore, there was no significant difference
      (p>0.05) in the water content (%) value for treatment times under 5min. Although
      the TBARS values gradually increased with increase in APP jet treatment times,
      these TBA values were below 1.0mgMA/kg (an indicator of meat rancidity). The
      results of the current study indicate that 5min of APP jet treatment showed >99%
      reduction (2log10PFU/mL) of MNV-1 titer and >90% reduction (1log10PFU/mL) of HAV
      titer without concomitant changes in meat quality; thus, this procedure can be
      considered in fresh meat production, processing and distribution processes to
      enhance fresh meat safety.

PMID- 28455014
TI  - Gastrointestinal digestion of dairy and soy proteins in infant formulas: An in
      vitro study.
AB  - An in vitro digestion simulating infant gastrointestinal tract studied the
      digestion of caseins, whey and soy proteins, commonly used in infant
      formulations, in the presence of proteases only (without lipolytic enzymes).
      60min of gastric phase and 120min of intestinal phase coupled with gel
      electrophoresis, confocal microscopy, mastersizer and pH were employed to monitor
      the degradation of proteins, microstructure, particle size distribution and pH
      drop of the digesta through the in vitro digestion process. Obtained results
      showed around 20% of caseins and almost no components of whey were hydrolysed
      after 60min in the simulated stomach. In the simulated duodenal phase, 8% of
      alpha-lactalbumin was hydrolysed while caseins and beta-lactoglobulin completely
      digested immediately and 30min respectively after addition of duodenal digestive
      proteases. Overall, soy proteins indicated lower level of hydrolysis than dairy
      proteins during in vitro infant digestion as observed by SDS-PAGE. The soy
      protein fractions glycinin and beta-conglycinin were partially hydrolysed during
      the gastrointestinal phase. The observed pH drop confirms that caseins are easily
      digested in the duodenal phase compared to whey and soy protein. Gastric
      digestion resulted in a decrease of the particle size of protein aggregates, but
      no fat coalescence was observed during both gastric and duodenal digestions in
      the given conditions.

PMID- 28455015
TI  - Pitfalls of using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay to assess the
      radical scavenging activity of peptides: Its susceptibility to interference and
      low reactivity towards peptides.
AB  - DPPH assay is widely used to evaluate the radical scavenging activities of
      peptides. Effects of pH and buffers on the stability of DPPH* and its reduced
      product (DPPHH) in the ethanol-buffer solution were investigated in this study
      and the reactivity of DPPH* towards several dipeptides was compared to that of
      2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) and the peroxyl
      radicals in oxygen radical absorbance capacity (ORAC) assay. Results showed that
      the deprotonation of DPPHH under basic condition could interfere with the
      spectrophotometric measurement at 515-525nm. It was suggested that the reaction
      mixture be maintained at a final pH range of 5.0-6.5 in 1:1 ethanol
      acetate/citrate buffer medium when evaluating the activities of peptides.
      Additionally, among tested dipeptides, only Cys-containing dipeptides displayed
      DPPH* scavenging activity with 0.14-0.28MUmol TE (Trolox equivalent)/MUmol, while
      Tyr/Trp-containing dipeptides with high reactivity towards ABTS*+ and peroxyl
      radicals were inert to DPPH* with TE values less than 0.02.

PMID- 28455016
TI  - Antihyperlipidemic and antihyperglycemic effects of the Brazilian salsaparrilhas
      Smilax brasiliensis Spreng. (Smilacaceae) and Herreria salsaparrilha Mart.
      (Agavaceae) in mice treated with a high-refined-carbohydrate containing diet.
AB  - Roots of Smilax species (Smilacaceae), named as salsaparrilha, have been used for
      centuries in Asia and Americas as depurative (=for "cleaning blood"), diuretic
      and sudorific. In southeast of Brazil, roots of Herreria salsaparrilha Mart.
      (Agavaceae) are also named as salsaparrilha and are used for the same purpose. In
      this study, we have evaluated the antihyperlipidemic and antihyperglycemic
      effects of extracts from roots of Smilax brasiliensis and H. salsaparrilha in
      mice fed with high-refined carbohydrate diet (HC). The chemical composition of
      the products was determined by LC-DAD and LC-MS. Groups of mice that received the
      HC diet showed an increase in plasma concentrations of glucose, triglycerides and
      total cholesterol, compared to control group, without treatment (p<0.05).
      Triglycerides were reduced significantly (p<0.05) in HC diet group that received
      100 and 200mg/kg BW/day of both salsaparrilha extracts. Glucose and total
      cholesterol levels were reduced significantly (p<0.05) in the groups that
      received the higher doses (200mg/kg BW/day) of both extracts of salsaparrilha.
      Extracts of S. brasiliensis, at this dose also showed a higher reduction in
      triglycerides levels (p<0.001) and promoted a significant reduction in the
      adipocyte area (p<0.05). Both extracts showed the presence of saponins in LC
      analysis but S. brasiliensis has a higher concentration of phenolics, mainly
      chlorogenic acid. The presence of steroidal saponins might be responsible for the
      reduction of the cholesterol levels, while phenolics in S. brasiliensis by the
      metabolism of triglycerides and better fat distribution. The result is according
      with the traditional use of these plants and shown their potential for use as
      functional foods.

PMID- 28455017
TI  - A comprehensive review on in vitro digestion of infant formula.
AB  - Although mothers' milk is the best food for babies, infant formula has become an
      alternative when breastfeeding is not possible or inadequate for babies. To
      design a proper formula for babies, understanding digestibility of macronutrients
      and their bio-accessibility in the gastrointestinal tract is essential. In vivo
      gastrointestinal studies on human infants are restricted by ethical constraint,
      cost issues, and intensive resource. However, in vitro models offer many
      advantages with low cost, easy sampling accessibility and no ethical issues. This
      article aims at reviewing the main aspects of the infant physiological
      gastrointestinal tract and providing an insight on recent in vitro research on
      infant formula.

PMID- 28455018
TI  - Discovery of characteristic chemical markers for inspecting sulfur-fumigated
      Radix Angelicae Sinensis by ultra-high performance liquid chromatography
      quadrupole/time-of-flight mass spectrometry based metabolomics and chemical
      profiling approach.
AB  - An UHPLC-QTOF-MS/MS based metabolomics and chemical profiling approach was
      developed to identify the characteristic chemical markers for inspecting sulfur
      fumigated Radix Angelicae Sinensis (S-RAS). Two sulfur-containing compounds in S
      RAS were discovered and deduced to be (3Z)-6-sulfite-ligustilide and (3E)-6
      sulfite-ligustilide. Furthermore, utilizing extraction ion method with the
      typical ion (m/z 271.06) of (3Z)-6-sulfite-ligustilide/(3E)-6-sulfite-ligustilide
      as the diagnostic ion, another six sulfur-containing components were determined
      in S-RAS, and identified as 6, 8-disulfite-ligustilide and 8-sulfite-ligustilide
      or their isomers. The generation mechanisms of these compounds were proposed as
      the addition reaction of sulfurous acid with (Z)-ligustilide and/or (E)
      ligustilide, two major naturally occurring components in RAS, at the double bonds
      of C6C7 and C3C8 positions. Using (3Z)-6-sulfite-ligustilide and (3E)-6-sulfite
      ligustilide as the chemical markers, fourteen of sixteen batches of commercial
      RAS samples were inspected to be S-RAS, suggesting that the newly generated
      sulfur-containing compounds could be used as characteristic chemical markers for
      inspecting S-RAS among commercial RAS samples.

PMID- 28455019
TI  - Positive impact of a functional ingredient on hunger and satiety after ingestion
      of two meals with different characteristics.
AB  - The ingestion of unavailable carbohydrates - functional ingredients - has
      presented an inverse relationship with the risk for chronic non-communicable
      diseases. The objective of this work was to evaluate the effects of addition of
      inulin to two ready-to-eat frozen meals on the release of gastrointestinal
      hormones and other parameters related to hunger and satiety. Prototypes of two
      different kinds of frozen meals were elaborated by the food industry: control
      meal (C1 and C2); and test meals, added inulin (T1 and T2). Three sequential
      clinical assays were performed with healthy volunteers: 1) evaluation of glycemic
      response (n=16); 2) evaluation of gastrointestinal hormones related to satiety
      (n=15); and 3) evaluation of satiety (by Visual Analogue Scale - VAS and energy
      intake) (n=52). The meals showed low glycemic index and glycemic load, and T1
      showed a decreased glycemic response peak compared to C1. The addition of inulin
      (~8g) to the test meals (lunch) provided significant satiety, resulting in an
      decrease in energy intake of 419 (group 1) and 586kJ (group 2) in the two
      subsequent meals (after 180min and 360min) and a decrease in hunger and increase
      in satiety at 120 and 180min when comparing with control meals. A positive post
      prandial variation was observed in the plasmatic levels of ghrelin and insulin in
      relation to the control meal (hormones related to hunger in high levels), after
      the intake of both two test meals. Inulin is an ingredient that presents several
      positive characteristics for the elaboration of products that stimulate healthy
      eating habits. These effects are currently being evaluated in medium-term trials.

PMID- 28455020
TI  - Effect of extruded wheat flour and pre-gelatinized cassava starch on process and
      quality parameters of French-type bread elaborated from frozen dough.
AB  - This study aimed to verify the potential of extruded wheat flour (EWF) or pre
      gelatinized cassava starch (PGS) to improve the process and the quality of French
      bread elaborated from frozen dough. Three formulations were prepared: 100%
      control wheat flour (CWF) and the other two formulations with 5% substitution of
      wheat flour by EWF or PGS. Frozen doughs were frozen stored for seven days and
      after this period they were thawed, fermented, baked and evaluated for physical,
      chemical and technological characteristics. Available glucose levels found for
      EWF (12g/100g), and PGS (11.7g/100g) in relation to CWF (7.1g/100g) showed higher
      sugar availability for yeasts at the initial stage of proofing, and may also have
      had a cryoprotective effect when freezing bread doughs. The frozen doughs with
      EWF or PGS, when thawed and fermented, presented higher volume increase, but
      after baking, they presented lower volume when compared to the control bread. The
      results of this study are promising for the use of extruded wheat flour or pre
      gelatinized cassava starch as sugar providers for doughs' post-freezing proofing
      process, improving frozen dough process of French-type bread.

PMID- 28455021
TI  - First comprehensive characterization of volatile profile of north Moroccan olive
      oils: A geographic discriminant approach.
AB  - Herewith we have evaluated the variability of the composition in terms of
      volatile compounds of monovarietal "Picholine marocaine" olive oils and checked
      the possible influence of their geographical origin. For this purpose, 92 olive
      samples were collected during the harvesting period 2012/2013 from 7 north
      Moroccan regions, and the analysis of the volatile profiles of the obtained oils
      was performed by using headspace solid-phase microextraction coupled to gas
      chromatography with flame ionization and mass spectrometry detectors (HS-SPME/GC
      FID-MS). A total of 40 volatile compounds belonging to different chemical classes
      were identified and quantified. Significant differences in the concentration
      levels of volatile constituents from oils of different geographical origins were
      found. Furthermore, for testing the ability of the identified volatile compounds
      for the geographical origin discrimination of the investigated oils, a stepwise
      linear discriminant analysis (s-LDA) was applied. Results revealed a very
      satisfactory classification of the studied oils according their geographic
      origin.

PMID- 28455022
TI  - Foamy polystyrene trays for fresh-meat packaging: Life-cycle inventory data
      collection and environmental impact assessment.
AB  - Food packaging systems are designed to perform series of functions mainly aimed
      at containing and protecting foods during their shelf-lives. However, to perform
      those functions a package causes environmental impacts that affect food supply
      chains and that come from its life-cycle phases. Therefore, package design should
      be done based upon not only the issues of cost, food shelf-life and safety, as
      well as practicality, but also of environmental sustainability. For this purpose,
      Life Cycle Assessment (LCA) can be applied in the packaging field with the aim of
      highlighting environmental hotspots and improvement potentials, thus enabling
      more eco-friendly products. In this context, an LCA of foamy polystyrene (PS)
      trays used for fresh meat packaging was performed here. The study highlighted
      that the highest environmental impacts come from PS-granule production and
      electricity consumption. In this regard, the authors underscored that there are
      no margins for improvement in the production of the granules and in the transport
      of the material inputs involved as well as of the trays to users. On the
      contrary, changing the energy source into a renewable one (by installing, for
      instance, a wind power plant) would enable a 14% damage reduction. In this way,
      the authors documented that alternative ways can be found for global
      environmental improvement of the system analysed and so for enhanced
      environmental sustainability of food packaging systems.

PMID- 28455023
TI  - Modeling moisture migration in a multi-domain food system: Application to storage
      of a sandwich system.
AB  - Moisture transport in a food system involving two different materials of unequal
      moisture content was modeled with water activity as the driving force using a
      porous media framework. This model was applied to a bread-barbecue chicken pocket
      sandwich stored in isothermal conditions. The model successfully predicted the
      equilibrium condition, where the two materials, bread and chicken, reached the
      same water activity, but not the same water content. The transient changes in the
      moisture content in the bread and chicken were predicted and shown to be
      significantly affected by air gap between the bread and chicken. The prediction
      process was also sensitive to the Darcy permeability values for the materials.
      The modeling framework presented for a sandwich system is very general and can
      easily be extended to other multicomponent food systems.

PMID- 28455024
TI  - Molecular characterization of silver-stearate nanoparticles (AgStNPs): A
      hydrophobic and antimicrobial material against foodborne pathogens.
AB  - In this study, silver-stearate nanoparticles (AgStNPs) have been produced from
      silver nitrate solutions by replacing the nitrate by stearate ions and then
      reducing by thermal treatment. AgStNPs were characterized by particle size, zeta
      potential, ATR-FTIR, contact angle and SEM (scanning electron microscopy)
      analyses. The mean particle size and zeta potential of AgStNPs were determined to
      be 69.22+/-7.30nm and +8.02+/-0.88mV. ATR-FTIR analysis showed characteristic IR
      bands of stearate, revealing the two strong peaks at 2848 and 2915cm-1 associated
      to symmetric (nus(CH2)) and asymmetric (nuas(CH2)) stretching vibrations of
      methylene groups, respectively. On the other hand, the scissoring and rocking
      modes of methylene group were observed at 1470 and 718cm-1, respectively.
      Nanomorphological characterization by SEM revealed a layered morphology of
      AgStNPs. Contact angle measurements demonstrated that a contact angle of water
      drop on glass coated with AgStNPs was found to be 108.76 degrees , which proved
      the strong hydrophobic properties of AgStNPs. AgStNPs seemed to be very effective
      in inhibiting foodborne pathogens (Salmonella Typhimurium, Escherichia coli
      O157:H7, Staphylococcus aureus, Listeria monocytogenes and Candida albicans). The
      results suggest the use of AgStNPs as a coating material to reduce biofilm or
      biofouling formation in terms of achieving appropriate food contact surfaces and
      higher hygiene/easier sanitation due to their strong hydrophobic and
      antimicrobial properties.

PMID- 28455025
TI  - Metabolite profiling, antioxidant and antibacterial activities of Brazilian
      propolis: Use of correlation and multivariate analyses to identify potential
      bioactive compounds.
AB  - The production of propolis by honeybees results from a selective collection of
      exudates from various plant species and present many potentialities in the
      pharmaceutical industry. The objective of this study was to investigate the
      chemical profile of Brazilian propolis, as well as their in vitro antioxidant and
      antibacterial activities. Gas chromatography-mass spectrometry was applied for
      chemical profiling of propolis extracts. Total phenolic compounds were quantified
      by Folin-Ciocalteu and antioxidant properties were assessed by 2,2-diphenyl-1
      picrylhydrazyl radical scavenging assay. Antibacterial activity was assessed
      against Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus.
      Correlation and multivariate statistical analysis were used to identify potential
      bioactive compounds in the extracts. Twenty-nine metabolites were identified
      along with 34 other metabolites that were classified into the following classes:
      triterpenoids (12), acetyltriterpenoids (3), sesquiterpenes (6), steroids (4),
      and hydrocarbons (9). The antioxidant capacity (IC50) ranged from 21.50 to
      78.77MUg/mL, whereas the content of total phenolic compounds ranged from 31.88 to
      204.30mg GAE/g of dry weight. Total phenolic compounds and methyl retinoate
      showed a positive correlation with the antioxidant capacity, whereas
      tetradecanal, gamma-palmitolactone and ethyl hydrocinnamate showed a negative
      correlation. Different sets of metabolites are shown to correlate with the
      antibacterial activity of the extracts, which is largely dependent on the type of
      microorganism. This innovative approach allowed us to identify likely bioactive
      compounds in the extracts, although the mechanism(s) underlying antibacterial
      activity encompass a complex trait, which might involve synergistic effects.

PMID- 28455026
TI  - Optimal difference test sequence and power for discriminating soups of varying
      sodium content: DTFM version of dual-reference duo-trio with unspecified tetrad
      tests.
AB  - As sodium reduction has become very important in the food industry, various types
      of unspecified duo-trio tests have been studied to improve its efficiency for
      studying samples with high sodium content, and a constant-saltier-reference duo
      trio test with dual reference, one reference in the first position and the second
      reference in the middle between the two test stimuli (DTFM), has been
      recommended. For the duo-trio test, a 'comparison of distance' (COD) strategy has
      been generally assumed. Yet, theoretically for DTFM, the 2-AFC reminder (2-AFCR)
      tau-strategy is also possible, which would make DTFM more efficient than the
      unspecified tetrad test. In this study, the hypothesis was that when subjects are
      pre-exposed to two types of samples, the 2-AFCR tau-strategy can be adopted in a
      constant-reference DTFM using a fixed design experiment. In order to test this
      hypothesis, unspecified tetrad tests involving categorization tasks were used as
      a means of pre-exposure to the two types of samples for DTFM, and a performance
      comparison was conducted. Two groups of 39 untrained/naive subjects performed
      both the unspecified tetrad and DTFM tests in varying orders for the purpose of
      discriminating two different soup samples of varying sodium content. A comparison
      of the d' estimate across different methods supported the hypothesis that the
      more efficient 2-AFCR tau-strategy was appropriate when the tetrad test preceded
      DTFM, while when DTFM was performed first without pre-categorization of samples,
      the conventional duo-trio COD strategy was appropriate for the constant-reference
      DTFM.

PMID- 28455027
TI  - Detailed polyphenolic profiling of Annurca apple (M. pumila Miller cv Annurca) by
      a combination of RP-UHPLC and HILIC, both hyphenated to IT-TOF mass spectrometry.
AB  - Annurca apple, a Southern Italian cultivar, possesses not only a particular taste
      and flavor, different from other types of apple, but also several healthy
      properties. With the aim to thoroughly elucidate the polyphenolic profile of this
      variety, listed as Protected Geographical Indication product, an extensive
      qualitative profiling of Annurca apple polyphenolic peel extract was carried out,
      by employing a combination of ultra high performance reversed phase (RP-UHPLC)
      and hydrophilic liquid chromatography (HILIC) coupled to ion trap-time of flight
      (IT-TOF) mass spectrometry. A total of 63 compounds were tentatively identified,
      25 of which not reported in Annurca apple extract so far. Furthermore, thanks to
      the different selectivity obtained with the HILIC, in combination with accurate
      mass measurements, an improved separation and detection of procyanidins, was
      obtained. Moreover, the obtained profiles were compared with those of a
      conventional variety, such as Red Delicious (RD), highlighting their differences.
      This work contributes to increase the knowledge about the polyphenolic
      fingerprint of this typical apple variety.

PMID- 28455028
TI  - The mechanisms of the protective effects of reconstituted skim milk during
      convective droplet drying of lactic acid bacteria.
AB  - Reconstituted skim milk (RSM) is a reputed protective carrier for improving the
      survival ratio of lactic acid bacteria (LAB) after spray drying; however the
      underlying mechanisms of the prominent protection remains unclear. In this study,
      the inactivation histories of two LAB strains during droplet drying with four
      carriers were experimentally determined, and the effects of droplet drying
      parameters on LAB inactivation were investigated. For the first time, the
      possible contribution of each RSM components to the maintenance of LAB viability
      during drying was discussed. Rapid inactivation of LAB cells only started at the
      later stage of drying, where RSM could maintain viability better upon both high
      droplet temperature and low moisture content than the other three carriers
      tested. Such protective effects was attributed to calcium and milk proteins
      rather than lactose. Upon the rapidly increasing droplet temperature at the later
      stage, calcium might enhance the heat resistance of LAB cells, whereas proteins
      might lead to a mild temperature variation rate which was beneficial to cell
      survival. LAB cells dried in the reconstituted whole milk showed the most
      advanced transition of rapid viability loss, with transition temperature at
      around 60 degrees C, in contrast to 65-70 degrees C in lactose and MRS carriers
      and 75 degrees C in the RSM carrier. The detrimental effects could be due to the
      high level of milk fat content. The proposed effects of each RSM components on
      LAB viability would be useful for constructing more powerful protectants for
      production of active dry LAB cells via spray drying.

PMID- 28455029
TI  - A metabolomics approach for authentication of Ophiocordyceps sinensis by liquid
      chromatography coupled with quadrupole time-of-flight mass spectrometry.
AB  - Ophiocordyceps sinensis (DCXC) is a well-known traditional Chinese medicine that
      exhibits various health-promoting effects. However, counterfeits and mimics of
      DCXC are frequently found in markets. In the present study, we examined the
      potential of quadrupole time-of-flight mass spectrometry (QTOF-MS) coupled with
      ultrafast liquid chromatography (UFLC) for use in the authentication of DCXC.
      Metabolite fingerprinting was obtained and subjected to multivariate statistical
      analysis. Discrimination of genuine DCXC, its counterfeits, cultured mycelia, and
      mimics was carried out by principal component analysis-discriminant analysis (PCA
      DA). Furthermore, 18 characteristic markers efficiently distinguishing DCXC and
      its adulterants were selected by creation of profile plots displaying the
      abundances of markers. Determination of molecular formulae and tentative
      identification of marker compounds were conducted using elemental formula
      calculation and online database searches based on accurate MS mass and MS/MS
      fragmentation information. These results suggested that UFLC-QTOF-based
      metabolomics has great potential for the rapid detection of DCXC adulteration.

PMID- 28455030
TI  - Fast determination of intact glucosinolates in broccoli leaf by pressurized
      liquid extraction and ultra high performance liquid chromatography coupled to
      quadrupole time-of-flight mass spectrometry.
AB  - In this study, we investigate for the first time the efficiency of an
      environmentally sustainable extraction technique (pressurized liquid extraction,
      PLE) in conjunction with a fast separation technique (ultra-high performance
      liquid chromatography, UHPLC) coupled to a selective mass spectrometry (MS)
      detector (quadrupole time-of-flight, qTOF) to extract, separate and quantify
      fifteen intact-glucosinolates (GLSs) in broccoli leaves. Firstly, we have
      developed and optimized by means of an experimental design an efficient
      extraction procedure based on PLE (using ethanol/water as a solvent), giving
      complete extraction within 15min; meanwhile, the average analyte recoveries were
      between 85% and 96% in all cases. Chromatography was performed on a UHPLC BEH
      Shield RP18 1.7MUm 110A (2.1*100mm) analytical column with a mobile phase
      composed by formic acid in water (0.5%, v/v) and formic acid in acetonitrile
      (0.5%, v/v) in gradient elution mode at 0.3mL/min, resulted in baseline-separated
      peaks and a run time of 13min. The method was fully validated in terms of
      selectivity, limits of detection (LOD) and quantification (LOQ), linearity,
      precision, and trueness; meanwhile a study of the matrix effect was also
      performed. A good selectivity, low LODs and LOQs, ranging from 2 to 26MUg/g, wide
      linear ranges from LOQ to 2500MUg/g, and satisfactory precision and trueness with
      relative standard deviation and relative error values lower than or equal to 9%,
      were obtained for the studied GLSs. Finally, the proposed method was successfully
      applied to the analysis of intact-GLSs in fifteen broccoli leaf samples from
      three different cultivars (Parthenon, Nubia, and Naxos). Nine intact-GLSs were
      detected in all the varieties, although in different concentrations, which ranged
      between 14 and 1136MUg/g, depending on the broccoli cultivar. In addition, the
      highest total content of GLSs was found in broccoli leaf samples from Parthenon
      cultivar, being the Naxos cultivar the poorest in GLS content. This study
      demonstrates the efficiency of PLE as an environmentally sustainable alternative
      to extract intact-GLS from broccoli leaves, and that UHPLC-qTOF-MS allowed a
      rapid, selective and sensitive determination of intact-GLSs in this matrix.

PMID- 28455031
TI  - Radical scavenging activity characterization of synthetic isochroman-derivatives
      of hydroxytyrosol: A gas-phase DFT approach.
AB  - Hydroxytyrosol (HT) and a set of synthetic isochroman derivatives of HT have been
      studied with regards to their radical scavenging activity in the gas employing
      density functional theory (DFT) and the Becke's 3 Lee Yang Parr (B3LYP)
      functional. Values of molecular descriptors (bond dissociation enthalpy, BDE;
      ionization potential, IP; proton dissociation enthalpy, PDE; proton affinity, PA;
      electron transfer energy, ETE; electron accepting power, omega+; electron
      donating power, omega-; net electrophilicity, Deltaomega+/-) characterizing the
      hydrogen atom or electron donating efficiency of test compounds were used.
      Published experimental findings for the radical scavenging activity of the same
      compounds using methods such as Rancimat, 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulphonic acid) radical cation and oxygen radical absorbance capacity were
      discussed. All the synthetic isochromans were predicted to be more potent
      hydrogen atom and electron donors than HT, though polarity may affect their
      performance in lipidic systems. Present findings point out that HT and examined
      isochromans prefer to scavenge free radicals via hydrogen atom transfer instead
      of electron donation and that allylic hydrogen atoms are expected to account for
      a higher activity in comparison to other phenolic antioxidants. The most potent
      hydrogen atom donor was the one bearing two catechol groups which can form
      stepwise a di-quinone and then scavenge additional radicals via allylic hydrogen
      atom donation and subsequent adduct formation. The total enthalpy required for
      all hydrogen atoms donated by test compounds was the most appropriate index of
      experimental activity prediction instead of common descriptors.

PMID- 28455032
TI  - The influence of glycosylation on the antigenicity, allergenicity, and structural
      properties of 11S-lactose conjugates.
AB  - Soybean is nutritious and is an excellent source of high-quality protein for
      human food and animal feed. However, glycinin (11S) is considered as the major
      allergenic protein that causes soybean allergies. Glycosylation is widely used to
      remove food protein allergens. In this study, soybean 11S was isolated and used
      in a glycation reaction with lactose at a weight ratio of 4:1 at 55 degrees C and
      79% relative humidity for different periods of time. The effects of glycosylation
      on the antigenicity and residual allergenicity of 11S were investigated, using
      the specific IgG polyclonal antibodies for glycinin and soy-allergic patient sera
      by indirect competitive, enzyme-linked immunosorbent assay (indirect competitive
      ELISA). Meanwhile, the degree of glycation was determined by the trinitrobenzene
      sulfonic acid (TNBS) method. The structural properties of 11S-lactose conjugates
      were characterized by SDS-PAGE, Fourier transform infrared spectrum (FTIR), and
      ultraviolet spectroscopy. Glycosylation effectively decreased the antigenicity
      and allergenicity of 11S if we increased the reaction time. The antigenicity of
      11S after glycosylation was reduced by approximately 30% compared with raw 11S,
      while allergenicity of 11S was reduced by 9%. The changes in secondary structures
      of glycated 11S may have influenced the allergic epitopes of protein. Therefore,
      we suggest that introducing lactose in 11S is an effective method to remove the
      antigenicity and allergenicity of glycinin.

PMID- 28455033
TI  - Hydrophobicity exerts different effects on bioavailability and stability of
      antioxidant peptide fractions from casein during simulated gastrointestinal
      digestion and Caco-2 cell absorption.
AB  - Alcalase-treated casein hydrolysates were separated into three hydrophobic
      chromatography fractions (HC-F1, HC-F2 and HC-F3) using YMC ODS C18 column.
      Simulated gastrointestinal (GI) digestion (stage I digestion) and Caco-2 cell
      absorption (stage II digestion) were sequentially applied for producing
      corresponding digests and adsorbates of collected peptide fractions. ANS probe
      and reverse-phase (RP)-HPLC were applied to detect peptide hydrophobicity,
      whereas trolox equivalent antioxidant capacity and oxygen radical antioxidant
      capacity were used to determine their antioxidant activity. Peptide nitrogen was
      used to evaluate bioavailability (BA) and remaining peptide content. In addition,
      RP-HPLC and electrospray ionization mass spectrometry were performed to obtain
      peptide sequences. Results showed that high hydrophobic peptide fractions (HC-F3)
      had excellent BA and remaining antioxidant activity, but poor digestive stability
      in stage I digestion. Two peptides, NTVP and IV, were identified from the
      adsorbate of HC-F3 to be GI-resistant peptides. Therefore, utilizing high
      hydrophobic peptides from casein as potential functional foods or nutraceuticals
      was feasible.

PMID- 28455034
TI  - Influence of evoked contexts on consumers' rejection of two products:
      Implications for shelf life estimation.
AB  - Consumers' increasing demand for fresh, safe and high quality products requires
      food companies to accurately estimate sensory shelf life and tolerance limits for
      sensory defects. Sensory shelf-life and acceptance limits for sensory defects
      have been estimated with consumers' rejection data using survival analysis
      without considering contextual variables, which could have a major influence on
      consumers' perception. The aim of the present study was to study how consumers'
      rejection is affected by different evoked contexts in a laboratory setting. Two
      studies were carried out to study the influence of evoked contexts on consumers'
      rejection. In the first study consumers' rejection for consumption at home and
      purchase at a supermarket was compared using orange juice samples with different
      storage times. In the second study, consumers' rejection for consumption at home
      and purchase at a supermarket for brands of different familiarities was compared
      using dulce de leche with different plastic flavour intensities as samples.
      Consumers' rejection data were analysed using survival analysis. The use of
      written scenarios to evoke different contexts affected consumers' rejection of
      products with different storage times and intensities of a sensory defect. Shelf
      lives that were estimated based on consumers' rejection to purchase were shorter
      than those estimated considering consumers' rejection to consume. In the second
      study, consumers' rejection under the consumption at home evoked context was
      similar to rejection to repeat purchase of a usual brand. However, a large
      difference existed between the evoked contexts that involved a usual and a new
      brand. Consumers were harsher when considering to repeat purchase of a new brand
      compared to their usual brand. These results suggest that the consideration of
      evoked contexts could contribute to increase the accuracy of sensory shelf life
      estimation and acceptance limits of sensory defects, leading to more informed
      business decisions.

PMID- 28455035
TI  - In vitro study on the cell adhesion ability of immobilized lactobacilli on
      natural supports.
AB  - The aim of the present study was to investigate the effect of probiotic
      immobilization onto wheat grains, both wet and freeze dried, on the adhesion
      properties of the probiotic cells and make comparisons with wet and freeze dried
      free cells. Lactobacillus casei ATCC 393 and Lactobacillus plantarum NCIMB 8826
      were used as model probiotic strains. The results showed satisfactory adhesion
      ability of free cells to a monolayer of Caco-2 cells (>1000CFU/100 Caco-2 cells
      for wet cells). Cell immobilization resulted in a significant decrease in
      adhesion, for both wet and freeze dried formulations, most likely because
      immobilized cells did not have direct access to the Caco-2 cells, but it still
      remained in adequate levels (>100CFU/100 Caco-2 cells for wet cells). No clear
      correlation could be observed between cell adhesion and the hydrophobicity of the
      bacterial cells, measured by the hexadecane adhesion assay. Most notably,
      immobilization enhanced the monolayer integrity of Caco-2 cells, demonstrated by
      a more than 2-fold increase in transepithelial electrical resistance (TEER)
      compared to free cells. SEM micrographs ascertained the adhesion of both
      immobilized and free cells to the brush border microvilli. Finally, the impact of
      the food matrix on the adhesion properties of probiotic bacteria and on the
      design of novel functional products is discussed.

PMID- 28455036
TI  - Aroma compounds in Ontario Vidal and Riesling icewines. I. Effects of harvest
      date.
AB  - Icewine is a sweet dessert wine made from pressing grapes naturally frozen on the
      vines. It is likely that freeze/thaw cycles endured by icewine grapes change
      their chemical and sensory profiles due to climatic events. Our objective was to
      determine the influence of harvest date on icewine must and wine basic chemical
      variables and aroma compounds. Riesling and Vidal icewines were made from grapes
      picked between December 2004 and February 2005; Harvest 1 (H1): 19 December;
      Harvest 2: 29 December; Harvest 3 (H3): 18 January; and Harvest 4 (H4): 11
      February (Vidal only). Icewine musts differed in titratable acidity and pH (Vidal
      only). All basic wine chemical analytes differed across harvest dates. All aroma
      compounds differed in Vidal and Riesling wines. Highest concentrations for most
      aroma compounds were in the last harvest date; 16 of 24 for Vidal and 17 of 23
      for Riesling. The latest harvest date had highest ethyl isobutyrate, ethyl 3
      methylbutyrate, 1-hexanol, 1-octen-3-ol, 1-octanol, cis-rose oxide, nerol oxide,
      ethyl benzoate, ethyl phenylacetate, gamma-nonalactone and beta-damascenone. H1
      had highest ethyl butyrate, ethyl hexanoate, linalool, 4-vinylguaiacol and ethyl
      octanoate. Based on odor activity values, the most odor-potent compounds were
      beta-damascenone, cis-rose oxide, 1-octen-3-ol, ethyl octanoate, ethyl hexanoate,
      and 4-vinylguaiacol across harvest dates. PCA found most aroma compounds
      associated with the last harvest date, 4-vinylguaicol excepted, which was
      associated with H1. Harvest date was considered a discriminating dimension using
      canonical variant analysis for volatile compounds.

PMID- 28455037
TI  - Aroma compounds in Ontario Vidal and Riesling icewines. II. Effects of crop
      level.
AB  - Icewine is a dessert wine of substantial commercial value to the Canadian wine
      industry. Many grapegrowers crop icewine-designated vines at levels double those
      for table wines; therefore, the experimental objective was to ascertain whether
      reducing crop level might impact icewine chemical and aroma compound profiles.
      Three treatments [control (fully-cropped); cluster thin at fruit set to one
      (basal) cluster per shoot (TFS); cluster thin at veraison (TV)] were evaluated in
      randomized block experiments for Riesling and Vidal over two seasons (2003-04;
      2004-05). Treatments differed in must pH and titratable acidity (both years) and
      although wines differed for most standard chemical variables, no clear trends
      existed. Vidal icewines had the highest aroma compound concentrations in the
      control and TV (2003) and in TFS (2004). Most Vidal aroma compounds differed with
      crop level: 17/24 (2003) and 23/24 (2004). Vidal odor activity values (OAVs) were
      highest for: beta-damascenone, ethyl octanoate, cis-rose oxide, 1-octen-3-ol,
      ethyl hexanoate, isoamyl acetate (2003); beta-damascenone, 1-octen-3-ol, ethyl
      octanoate, cis-rose oxide, and ethyl hexanoate (2004). Principal component
      analysis (PCA) found beta-damascenone, ethyl 2- and 3-methylbutyrate, ethyl
      isobutyrate, ethyl butyrate and 1-heptanol correlated and associated with the
      control (2003), but most compounds were positively loaded on PC1 and associated
      with replicate, not crop level (2004). All Riesling aroma compounds differed with
      crop level (2003) and 22/23 (2004). Both years, most aroma compounds were highest
      in TV and lowest in TFS wines. Riesling OAVs were highest for: beta-damascenone,
      ethyl octanoate, and ethyl hexanoate (2003, 2004); cis-rose oxide was highly odor
      potent (2004). PCA of Riesling showed most compounds loaded on PC1 and associated
      with TV wines (2003). Freeze/thaw events in November/December appeared more
      important in aroma compound development than adjustment of crop level, and it is
      therefore concluded that reduction of crop level in Vidal and Riesling vines
      would not substantially impact icewine aroma composition.

PMID- 28455038
TI  - Methodology for determination of two new sensory thresholds: Compromised
      acceptance threshold and rejection threshold.
AB  - The existing methodologies for determining thresholds generate unreliable
      estimates of the point at which the intensity of a stimulus begins to compromise
      acceptance or result in sensory rejection of a product. Thus, a new methodology
      was proposed for determination of two new sensory thresholds: the compromised
      acceptance threshold (CAT) and the rejection threshold (RT). In this new
      methodology, increasing or decreasing series of stimulus intensity are measured
      together with a standard stimulus (control sample) by means of acceptance tests.
      In the present study, the CAT and RT were determined for sucrose concentrations
      in grape nectar, demonstrating that when reducing the sucrose concentration of
      grape nectar form 9.00% (w/v) to 6.87% there begins to occur impairment of
      product acceptance (CAT), and when reducing the sucrose concentration from 9.00%
      to 3.83% there begins to occur sensory rejection (RT) of the product. When
      compared to existing threshold determination methodologies, the proposed
      methodology permitted for calculating, with greater reliability, the points at
      which compromise of acceptance (CAT) and sensory rejection (RT) of the product
      begin to occur. In addition to the case study presented, the proposed methodology
      has a wide range of applications in science and in the food, cosmetic and
      pharmaceutical industries.

PMID- 28455039
TI  - Flow and foam properties of extruded maize flour and its biopolymer blends
      expanded by microwave.
AB  - Maize flour and blends from starch and zein biopolymers were processed as dense
      materials by extrusion (120 degrees C, 300J.g-1) and press-molding (140 degrees
      C, 10min) at a constant moisture content (26%wb), and then foamed by microwave
      heating. The mechanical properties of foams, determined by a 3-point bending
      test, were governed by density, in agreement with an open solid foam model. The
      density and 3D cellular structure of the foams were determined by X-ray
      tomography. In the same interval of density [0.15, 0.3g.cm-3], foams from
      microwaved materials had a finer cellular structure than directly expanded
      materials at extruder outlet. The study of melt rheological behavior with
      Rheoplast(r) (100-160 degrees C, SME<=200J.g-1) showed that protein content (0
      15%) did not affect shear viscosity but increased elongational viscosity. This
      trend, similar to the one reported for the storage modulus in a rubbery state,
      could be attributed to dissipative effects in a starch/protein interphase,
      explaining the difference of expansion between starch, blends and flour.

PMID- 28455040
TI  - Hydrosols of orange blossom (Citrus aurantium), and rose flower (Rosa damascena
      and Rosa centifolia) support the growth of a heterogeneous spoilage microbiota.
AB  - Hydrosols are hydrodistillation products of aromatic plants. They contain less
      than 1g/L of dispersed essential oils giving organoleptic properties. Hydrosols
      are subjected to microbial proliferation. Reasons for spoilage have to be found
      in the nature of substrates supporting growth and of microbiological
      contaminants. The composition in essential oils and the microbiota of 22 hydrosol
      samples of Citrus aurantium L. ssp. amara L. (orange blossom), Rosa damascena
      Miller (rose D.), and Rosa centifolia L. (rose C.) flowers were analyzed to
      determine the factors responsible for decay. The median concentrations in
      essential oils were 677mg/L for orange blossom hydrosols, 205mg/L for rose D.
      hydrosols, and 116mg/L for rose C. hydrosols. The dry matter content of these
      hydrosols varied between 4.0mg/L and 702mg/L, and the carbohydrate content varied
      between 0.21mg/L and 0.38mg/L. These non-volatile compounds were likely carried
      over during distillation by a priming and foaming effect, and could be used as
      nutrients by microorganisms. A microbial proliferation at ambient temperature and
      also at 5 degrees C has been observed in all studied hydrosols when stored in a
      non-sterile container. In contaminated hydrosols, maximal counts were about
      7log10CFU/mL, while the French pharmacopeia recommends a maximal total bacterial
      count of 2log10CFU/mL. Neither yeast nor mold was detected. The isolated
      microbial population was composed of environmental Gram-negative bacteria,
      arranged in four major genera: Pseudomonas sp., Burkholderia cepacia complex, and
      presumably two new genera belonging to Acetobacteraceae and Rhodospirillaceae.
      Among those bacteria, Burkholderia vietnamiensis and Novosphingobium capsulatum
      were able to metabolize volatile compounds, such as geraniol to produce 6-methyl
      5-hepten-2-one or geranic acid, or phenylethyl acetate to produce 2
      phenylethanol. EO concentrations in hydrosols or cold storage are not sufficient
      to insure microbiological stability. Additional hurdles such as chemical
      preservatives or aseptic packaging will be necessary to insure microbial
      stability.

PMID- 28455041
TI  - Effect of temperature abuse on frozen army rations: Part 2: Predicting microbial
      spoilage.
AB  - Numerically simulated heat transfer model of frozen US military rations was
      combined with microbial kinetics to predict the microbial spoilage of the food
      products, during two possible temperature abuse scenarios. An army breakfast menu
      box containing five different food items was selected for conducting this
      research. One of the food item in the menu box, beefsteak, was chosen for
      detailed microbial study. A microbial predictive tool was used to identify and
      evaluate the kinetics of the most prone microorganism that can grow in a
      beefsteak. Numerical predictions suggested that the food items exposed to
      external temperatures ranging from 20 degrees C to 40 degrees C can be allowed to
      stay at those temperatures for maximum times of 28.7h to 11.9h, respectively. The
      food items can be allowed to stay inside the broken freezer for a maximum time of
      186h, to ensure microbial safety in the case of freezer failure.

PMID- 28455042
TI  - Effect of temperature abuse on frozen army rations. Part 1: Developing a heat
      transfer numerical model based on thermo-physical properties of food.
AB  - Numerical simulation was carried out to predict the effect of external
      temperature conditions on thermal behavior of frozen US military rations, during
      storage and transportation. An army breakfast menu box containing beefsteaks,
      concentrated orange juice, peppers & onions, French toast, and Danishes, was
      selected for conducting this study. Thermo-physical properties of each food item
      were characterized using their composition and differential scanning calorimeter
      (DSC). Apparent heat capacity method was used to account for the latent heat of
      phase change during simulation of thawing and freezing. Numerically simulated
      results were experimentally validated using a gel-based model food system and the
      food items in the menu box. The average deviation between numerically predicted
      temperature and experimentally measured temperature for the model food system was
      approximately 1 degrees C and for the targeted food items the deviation ranged
      from 2 degrees C to 5 degrees C, depending on the food item.

PMID- 28455043
TI  - Comparative evaluation of tannic acid inhibiting alpha-glucosidase and trypsin.
AB  - In this work, the inhibitory effects of tannic acid on the alpha-glucosidase and
      trypsin were systematically evaluated by comparing with the clinical diabetes
      healer acarbose and the soybean-derived trypsin inhibitor using fluorescence
      spectroscopy and enzymatic kinetics methods. We showed that the anti-alpha
      glucosidase activity of tannic acid (IC50=0.44MUg/mL) was higher than that of
      acarbose (IC50>0.60MUg/mL), while its anti-trypsin activity (IC50=0.79mg/mL) was
      significantly lower than that of the trypsin inhibitor from soybean
      (IC50<0.20mg/mL). Enzymatic kinetics measurements confirmed that the inhibitory
      pattern of tannic acid toward two tested enzymes was a mixed competitive and
      noncompetitive inhibition. Tannic acid could bind the enzymes to form new
      complexes, presenting a strong static fluorescence quenching. The presence of
      tannic acid led to the hypsochromic shift of the maximum fluorescence in trypsin,
      but not in alpha-glucosidase. The thermodynamic parameters indicated that the
      main driving force between tannic acid and both the enzymes was the hydrophobic
      interaction followed by the electrostatic interaction. Our work suggests that
      tannic acid is a strong anti-alpha-glucosidase natural inhibitor with a low
      inhibitory activity for trypsin, thus its roles in functional food and medicinal
      plants should be re-recognized.

PMID- 28455044
TI  - Hypertension parameters are attenuated by the continuous consumption of probiotic
      Minas cheese.
AB  - The aim of this study was to investigate the effects of ingestion of probiotic
      Minas Frescal cheese (PMFC) on hypertension parameters in spontaneously
      hypertensive rats (SHRs). Twenty-eight animals were divided into four groups fed
      with different experimental diets: control initial (CI), control final (CF),
      traditional Minas Frescal cheese (CMFC), and PMFC. The latter two groups were fed
      with 20g of cheese per day for 15days. All groups were assessed for blood
      pressure and health parameters. The results show that the group fed with PMFC
      exhibited significantly lower blood pressure when compared to the group fed with
      CMFC, CI, and CF. Regarding the other health parameters, an improvement in blood
      lipids (triglycerides and cholesterol) was observed for the group fed with PMFC
      as compared with CMFC. No significant differences were observed in renal function
      parameters. Our findings suggest that consumption of probiotic cheese can be
      potentially useful to improve the cardiovascular health parameters.

PMID- 28455045
TI  - Chemical properties and reactive oxygen and nitrogen species quenching activities
      of dry sugar-amino acid maillard reaction mixtures exposed to baking
      temperatures.
AB  - Maillard reaction products (MRPs) derived from 10 different, dry sugar-amino acid
      reaction model systems were examined for changes in color index (E), sugar loss,
      and formation of alpha-dicarbonyl compounds; the changes were correlated with
      relative activities to quench both reactive oxygen (ROS) and reactive nitrogen
      (RNS) species. Reducing sugars, xylose, ribose, fructose, glucose, and non
      reducing sucrose were reacted with glycine (Xyl-Gly, Rib-Gly, Fru-Gly, Glc-Gly,
      and Suc-Gly), or lysine (Xyl-Lys, Rib-Lys, Fru-Lys, Glc-Lys, and Suc-Lys),
      respectively, at temperatures of 150 degrees C and 180 degrees C for time periods
      ranging from 5 to 60min. ROS quenching capacity was negatively correlated with
      color index (E) (r=-0.604, P<0.001), and positively correlated with sugar loss
      (r=0.567, P<0.001). MRPs also exhibited activity to quench RNS as assessed by
      nitric oxide (NO) inhibition in differentiated Caco-2 cells that were induced
      with interferon-gamma (IFN-gamma) and phorbol ester (PMA) cocktail. We also
      showed a correlation between RNS and color index, sugar loss, and ROS quenching
      activities for MR mixtures that were heated for a short time (e.g. 10min) at 150
      degrees C. MRP quenching of ROS was largely influenced by sugar type, whereas,
      RNS quenching was dependent more so on the interaction between reactants and
      reaction conditions used to generate MRPs.

PMID- 28455046
TI  - A review of the bioactivity of coffee, caffeine and key coffee constituents on
      inflammatory responses linked to depression.
AB  - Coffee is a widely consumed beverage containing numerous biologically active
      constituents predominantly belonging to the polyphenol and alkaloid classes. It
      has been established that coffee has a beneficial effect on numerous disease
      states including depression. A number of prospective and retrospective cohort
      studies have assessed the effects of coffee consumption on the relative risk of
      developing major depressive disorder in humans. These studies have identified an
      inverse relationship between the consumption of caffeinated coffee and the risk
      of developing depression. Caffeine, chlorogenic acid, ferulic acid and caffeic
      acid, all important constituents of coffee, have been shown to possess biological
      activities that highlight a possible mechanistic link to the pathology of
      depression. This review aims to assess the evidence from the biological
      evaluation of these constituents of coffee on markers of inflammation associated
      with depression in in vitro and in vivo models of inflammation, neuroinflammation
      and depression. The ability of bioactive coffee constituents to modulate the
      parameters of neuroinflammation has been shown with caffeine having strong
      antioxidant properties in vitro, chlorogenic acid and caffeic acid having strong
      anti-inflammatory and antioxidant properties in vitro and ferulic acid having
      activities in in vivo animal models of depression.

PMID- 28455047
TI  - Identification of important mechanical and acoustic parameters for the sensory
      quality of cocoa butter alternatives.
AB  - In this study, the correlation between sensory attributes and the mechanical and
      acoustic properties of cocoa butter alternatives was elucidated. Needle
      penetration, cone penetration and compression tests were used to characterise
      mechanical properties and acoustic properties were evaluated by simultaneous
      texture and sound analyses. Results were correlated with a descriptive sensory
      evaluation. A significant correlation was found between hardness (needle
      penetration) and sensory hardness evaluated upon biting (r=0.91, p<0.05) and
      between Hencky strain (compression test) and the sensory toughness (r=0.94,
      p<0.05). In contrast, no significant correlation was found between brittleness
      (cone penetration) and the sensory brittleness. The use of different mechanical
      methods shed light on a complex rheological behaviour of fat which demonstrates
      the importance of not simply relying on results from penetration tests when
      evaluating fat texture. For instance, a hard fat was perceived very differently
      depending on the degree of elasticity. A significant correlation was found
      between sound pressure level (simultaneous sound and texture analyses) and the
      sensory evaluation of the sound intensity upon breakage (r=0.96 and 0.97,
      p<0.05). Both hardness and elasticity were found to be of great importance for
      the intensity of the sound emission i.e. a hard texture with a low degree of
      flexibility (less elastic) is more likely to provide a rapid energy release upon
      breakage and thus a high intensity sound emission.

PMID- 28455048
TI  - Assessment of the differences in the phenolic composition and color
      characteristics of new strawberry (Fragaria x ananassa Duch.) cultivars by HPLC
      MS and Imaging Tristimulus Colorimetry.
AB  - The phenolic composition (by HPLC-DAD-MS) and color characteristics (by Imaging
      Tristimulus Colorimetry) of four strawberry cultivars that have shown good
      climate adaptation to subtropical area (Nikte, Zamorana, Jacona and Pakal) have
      been assessed. 24 monomeric phenolics were identified, including 15 anthocyanins,
      5 phenolic acids, 1 flavanol and 4 flavonols. Nikte and Zamorana showed the
      highest phenolic potential mainly due to their higher content of anthocyanins,
      while Pakal was richer in phenolic acids. Regarding color, Nikte and Zamorana
      were the more similar cultivars having the lowest values of lightness and hue. On
      the contrary, the color of Pakal was quite different from all the rest, due to
      the specific distribution between pelargonidin and cyanidin. The inclusion of
      both phenolic and colorimetric information in the Linear Discriminant Analysis
      allowed reaching very good discriminations among cultivars.

PMID- 28455049
TI  - Effect of the smoking process and firewood type in the phytochemical content and
      antioxidant capacity of red Jalapeno pepper during its transformation to chipotle
      pepper.
AB  - Chipotle pepper is a dry smoked red Jalapeno pepper well appreciated in the
      Mexican and American cuisines. Phytochemical content and antioxidant activity of
      red Jalapeno pepper has been previously reported, however, the effect of the
      smoking process in the content of phytochemicals, antioxidant capacity and
      capsaicinoids has not been previously reported. In the present study we found
      that the smoking process had a significant effect on the content of polyphenolic
      compounds and antioxidant capacity of red Jalapeno pepper. It induced a nearly
      50% increase in total phenols and 15% increase in antioxidant capacity in
      chipotle pepper compared to fresh samples (in dry weight basis). Capsaicinoids
      and ascorbic acid content decreased in smoked samples, while carotenoids remained
      practically unchanged. The strongest effect of smoking was observed in the
      content of total flavonoids and catechin determined by HPLC. Therefore we can
      conclude that smoking process has a positive effect in the fruit because it
      raises its phytochemical properties. The type of wood used in the smoking process
      also had an effect on the phytochemical content and antioxidant capacity with
      traditional pecan wood being the best.

PMID- 28455050
TI  - Effects of pH on the formation of 4(5)-Methylimidazole in glucose/ammonium
      sulfate and glucose/ammonium sulfite caramel model reactions.
AB  - The objective of the present study was to detail the change of 4(5)
      Methylimidazole (4-MI) in sulfite and sulfate reactions with different initial pH
      values. Glucose/ammonium sulfate and glucose/ammonium sulfite reaction systems
      with initial pH conditions 4.9, 5.9, 6.9, 8.0 and 8.6, were heated at 100 degrees
      C for 2h, respectively. Higher concentration of methylglyoxal (MGO) and 4-MI was
      detected in thermal treated glucose/ammonium sulfite reaction system than that in
      sulfate system. The SO32- reacting with MGO and other precursors of 4-MI at
      higher pH conditions prevented 4-MI formation. However, no inhibition of 4-MI was
      found at lower pH conditions due to higher reactivity of the nucleophilic NH4+
      than SO32-. The browning intensity of the sulfite system changed scarcely at
      higher pH values, which was possibly caused by the polyreaction between SO32- and
      carbonyl, instead of the intermolecular polymerisation of carbonyl in the
      advanced stage of the Maillard reaction.

PMID- 28455051
TI  - Antioxidant potential of dietary chia seed and oil (Salvia hispanica L.) in diet
      induced obese rats.
AB  - This study aimed to investigate the effects of dietary chia seed and oil on
      plasma and liver oxidative status in diet-induced obese rats. Thirty-six Wistar
      rats were divided in six groups (6 animals each): control group was fed the
      American Institute of Nutrition (AIN)-93M diet; HFF group was fed a high-fat and
      high-fructose (HFF) diet; chia seed short (6-weeks) and long (12-weeks)
      treatments received an HFF diet with chia seed; chia oil short (6-weeks) and long
      (12-weeks) treatments received an HFF diet with chia oil. Plasma and hepatic
      biomarkers of lipid peroxidation, endogenous enzymatic and non-enzymatic
      antioxidant systems and antioxidant capacity were determined. HFF diet induced
      weight gain, oxidative stress and lipid peroxidation in plasma and liver of
      animals. Compared to HFF group chia seed and chia oil (12 and 6weeks) intake
      increased plasma reduced thiol (GSH) levels, plasma catalase (CAT) and
      glutathione peroxidase (GPx) activities. In the liver glutathione reductase (GRd)
      activity was enhanced, while CAT and GPx activities did not change. There were no
      differences in plasma and liver superoxide dismutase activity among chia diets
      and HFF group. Chia (seed and oil) intake did not modify liver lipid
      peroxidation, but was able to reduce plasma thiobarbituric acid reactive
      substances (TBARS) and 8-isoprostane levels increased by HFF group. Plasma and
      hepatic antioxidant capacity values were increased in chia seed and oil groups
      about 35% and 47%, respectively, compared to HFF group. Chia groups presented
      similar antioxidant potential, regardless of treatment time. Dietary chia seed
      and oil reduced oxidative stress in vivo, since it improved antioxidant status
      and reduced lipid peroxidation in diet-induced obese rats.

PMID- 28455052
TI  - The morphology of salt crystals affects the perception of saltiness.
AB  - High intake of salt (NaCl) has been associated with risk of non-communicable
      diseases, including hypertension, cardiovascular disease and stroke. Several
      strategies for reducing salt in foods are under study, including the relation of
      crystal morphology on dissolution properties of salt in the mouth. The aim of
      this paper was to study the dissolution of salt crystals with different
      morphologies in artificial saliva and to correlate the findings with the
      perception of saltiness over time. The morphology of five commercial salts was
      analyzed by scanning electronic microscopy and micro-CT studies. Shape parameters
      of crystals were determined using images from an optical microscope. Crystal
      dissolution in artificial saliva was evaluated using video-microscopy and the
      perception of saltiness was evaluated using sensorial test of time-intensity at
      standardized sodium content. Salt morphology was correlated well with dissolution
      rate and certain time-intensity parameters (time to maximum intensity, intensity
      at maximum and increase angle). Non-cubic and agglomerated crystals, such as
      Kosher and Maldon salts, were dissolved faster (dissolution rate up to 3.8 times
      higher) and experienced maximum saltiness (up to 17% more) at shorter times (up
      to 40% less). Crystal morphology may be a variable to consider to achieve sodium
      reduction while maintaining salt intensity.

PMID- 28455053
TI  - Monitoring of lactic fermentation driven by different starter cultures via direct
      injection mass spectrometric analysis of flavour-related volatile compounds.
AB  - In this work, we used Proton Transfer Reaction-Mass Spectrometry (PTR-ToF-MS),
      coupled with an automated sampling system, to monitor lactic fermentation driven
      by different yogurt commercial starter cultures via direct injection mass
      spectrometric analysis of flavour-related volatile compounds. The aim is the
      identification of markers for real-time and non-invasive bioprocess control and
      optimisation as an industrial driver of innovation in food technology and
      biotechnology. We detected more than 300 mass peaks, tentatively identifying all
      major yogurt aroma volatiles. Thirteen mass peaks showed statistically
      significant differences among the four commercial starters. Among these are
      acetaldehyde, methanethiol, butanoic acid, 2-butanone, diacetyl, acetoin, 2
      hydroxy-3-pentanone/pentanoic acid, heptanoic acid and benzaldehyde which play a
      key role in yogurt flavour. These volatile described the diverse flavour
      properties claimed by food biotechnological companies and, considering the
      possible contribution to yogurt flavour, are potential markers for the rapid
      screening of starter cultures and for the quality design in this fermentation
      driven production. The strength of our approach lies in the identification, for
      the first time, of specific depletion kinetics of four sulphur containing
      compounds occurring during fermentation (hydrogen sulphide, methanethiol, S
      methyl thioacetate/S-ethyl thioformate, pentane-thiol), which suggest a new
      possible protechnological feature of yogurt starter cultures.

PMID- 28455054
TI  - Production and structural characterization of solid lipid microparticles loaded
      with soybean protein hydrolysate.
AB  - The aims of this study were to produce and evaluate solid lipid microparticles
      (SLMs) loaded with soy protein hydrolysate (HP). The SLMs were produced by spray
      chilling with an active material and carrier ratio of 1:5 and 1:10 and in two
      feed preparations: emulsion and suspension. The rheological parameters of the
      feeds produced by emulsions were studied, morphological characteristics of the
      SLMs were examined via scanning electron microscopy (SEM) and confocal
      microscopy, the particle size and distribution were measured via laser light
      diffraction, and the structural properties of the SLMs were characterized via
      infrared (FTIR) spectroscopy and X-ray diffraction (XRD). SEM images showed that
      SLMs were spherical and agglomerated. The analysis of X-ray diffraction indicated
      that the microparticles after 90days of storage had beta polymorphic form. The
      preparation methods for feeds, emulsion and suspension, had no influence on the
      rheological parameters, and the median particle size of the SLMs and interactions
      between the ingredients were not detected via FTIR spectroscopy; however, the
      SLMs prepared by emulsion contained pores and had a higher incorporation
      efficiency of HP. The spray chilling technique is suitable method for
      microencapsulation of soy protein hydrolysate. So, this technique could be useful
      for attenuating HP unpleasant taste, for its protection and also for promoting
      its release in the intestine, during fat digestion.

PMID- 28455055
TI  - Pre-drying and submerged cap winemaking: Effects on polyphenolic compounds and
      sensory descriptors. Part II: BRS Carmem and Bordo (Vitis labrusca L.).
AB  - Brazilian wine production is dominated by the use of American grape cultivars
      (Vitis labrusca L.) and their hybrids. In this context, this study analyzed the
      phenolic composition and sensory profile of Bordo and BRS Carmem red wines
      elaborated from traditional and two alternative winemaking technologies: grape
      pre-drying and submerged cap of chaptalized musts. Anthocyanins and
      pyranoanthocyanins apparently seemed to be affected by the thermal process (60
      degrees C), causing their degradation. In addition, the decrease of the
      concentration of these compounds could be suggested as a result of possible
      oxidation and hydrolysis reactions of anthocyanin 3-glucosides. Stilbenes were
      also affected by thermal degradation; however, flavan-3-ols and HCAD seemed to be
      less affected by the drying process. Submerged cap winemaking resulted in an
      increase of the anthocyanin and pyranoanthocyanin compounds due to the constant
      contact between the must and pomace during the alcoholic fermentation. The
      antioxidant capacity seemed not to be affected by thermal degradation, since the
      products of Maillard reaction also present antioxidant properties. Pre-dried
      wines were described as structured due to their higher flavan-3-ols content, and
      with high color intensity probably due to the formation of Maillard reaction
      products. The submerged cap wines presented an intense violet hue due to their
      high anthocyanin derivative concentrations and showed strong correlation with all
      other classes of the phenolic compounds.

PMID- 28455056
TI  - Conversion of ginsenosides by Lactobacillus plantarum studied by liquid
      chromatography coupled to quadrupole trap mass spectrometry.
AB  - Ginsenosides are the active components responsible for the pharmacological
      properties of ginseng, a commonly used medicinal plant and food ingredient. This
      study aimed to determine the changes of ginsenosides during fermentation of
      ginseng extract or reference ginsenosides with Lactobacillus plantarum.
      Chemically acidified ginseng extracts served as controls. High performance liquid
      chromatography coupled with quadrupole-trap (Q-TRAP) mass spectrometry method was
      employed for analysis and quantification of ginsenosides, and for identification
      of metabolites. A total of 14 metabolites were identified; the quantification of
      metabolites was achieved by tandem mass spectrometry in MRM mode. Metabolism of
      L. plantarum removed glucosyl moieties from ginsenosides Rb1, Rd, and Re at the C
      20 position to produce a racemic mixture of products. Remarkably, removal of
      glycosyl residues occurred not only by hydrolysis but also by dehydration to
      produce racemic mixtures of Delta20(21) or Delta20(22) products.
      Biotransformation occurred more rapidly with the di-substituted ginsenoside Rb1
      when compared to the mono-substituted ginsenoside Rd. This study thus extends the
      knowledge of biotransformation of ginsenosides to produce bioactive derivatives.

PMID- 28455057
TI  - Functional and physicochemical properties of a protein isolate from AluProt-CGNA:
      A novel protein-rich lupin variety (Lupinus luteus).
AB  - This study describes the isolation of proteins from the novel lupin variety
      AluProt-CGNA (Lupinus luteus) and the influence of pH and NaCl on their
      functional properties. AluProt-CGNA variety showed to have a great protein
      content in dehulled seeds (60.60g protein/100g, dry matter), which is higher than
      soybean and other lupin varieties. A lupin protein isolate (97.54g protein/100g)
      from AluProt-CGNA, LPIA, was prepared from lupin flour by alkali solubilization
      and isoelectric precipitation. The solubility profile of the LPIA was affected by
      pH, where the minimal values were observed at pH values close to its isoelectric
      point range (pH4-5). The highest values of water absorption capacity
      (1.71cm3H2O/g protein), oil absorption capacity (1.43g trapped oil/g protein),
      emulsifying capacity (61.94%), emulsion stability (96.43%), foaming capacity
      (114.29%), foam stability (65.69%) and least gelation concentration (20g/100cm3)
      were observed at pH values lower and higher than its isoelectric point. In the
      presence of 100mM of NaCl, their functional properties were improved. SDS-PAGE
      showed that LPIA mainly contained high molecular weight proteins (alpha and beta
      conglutin). These results are useful for increasing the utilization of this
      protein isolate as a potential functional ingredient in food industry.

PMID- 28455058
TI  - Check all that apply and free listing to describe the sensory characteristics of
      low sodium dry fermented sausages: Comparison with trained panel.
AB  - The urgent need for sodium reduction in meat products to enable healthy food
      choices has led food industry to search for more dynamic and fast methodological
      approaches to assess the sensory characteristics of their products. In the
      present study, dry fermented sausages with reduction in NaCl, replaced by KCl,
      CaCl2, and a blend of KCl and CaCl2 were evaluated for their sensory properties
      using a check all that apply questionnaire (CATA) and a free listing task. The
      results were compared with those of a trained panel using quantitative
      descriptive analysis (QDA). The absence of concordance was observed between the
      CATA and free listing towards the two bidimensional sensory maps and
      configuration of the samples in comparison to QDA. However, free listing was able
      to generate a similar and resumed vocabulary when compared to QDA. Our findings
      suggest the potential of free listing as sensory descriptive methodology in the
      development of reformulated food products with respect to sodium reduction.

PMID- 28455059
TI  - Carotenoids from fruits and vegetables: Chemistry, analysis, occurrence,
      bioavailability and biological activities.
AB  - Fruits and vegetables are generally considered as important contributors to a
      healthy diet and their intake is extremely helpful to reduce the risk of specific
      diseases like cancers, cardiovascular diseases, neural tube defects, and
      cataracts. Bioactive constituents from fruits and vegetables, such as
      carotenoids, folic acid and dietary fiber appear to play important roles in the
      prevention of these diseases. Carotenoids and their derivatives are versatile
      isoprenoids and play a vital role in plants and animals, starting from cellular
      antioxidant to gene regulation and so their importance at cellular and molecular
      level is well established. The most significant aspect of carotenoids in our diet
      is the antioxidant and provitamin A activity, and also the color that they impart
      to our food. The composition and bioavailability of carotenoids in food are
      significantly influenced by processing and other post-harvest technologies. This
      review discusses the theoretical aspects and recent developments in structural
      properties, biosynthesis and enhancement, processing, methods of analysis,
      composition in fruits and vegetables, and bioaccessibility and bioavailability of
      carotenoids. Additionally, future research challenges in this context are
      identified.

PMID- 28455060
TI  - Simulation and flavor compound analysis of dealcoholized beer via one-step vacuum
      distillation.
AB  - The coupled operation of vacuum distillation process to produce alcohol free beer
      at laboratory scale and Aspen HYSYS simulation software was studied to define the
      chemical changes during the dealcoholization process in the aroma profiles of 2
      different lager beers. At the lab-scale process, 2 different parameters were
      chosen to dealcoholize beer samples, 102mbar at 50 degrees C and 200mbar at 67
      degrees C. Samples taken at different steps of the process were analyzed by HS
      SPME-GC-MS focusing on the concentration of 7 flavor compounds, 5 alcohols and 2
      esters. For simulation process, the EoS parameters of the Wilson-2 property
      package were adjusted to the experimental data and one more pressure was tested
      (60mbar). Simulation methods represent a viable alternative to predict results of
      the volatile compound composition of a final dealcoholized beer.

PMID- 28455061
TI  - Enhanced stability of anthocyanin-based color in model beverage systems through
      whey protein isolate complexation.
AB  - Anthocyanins are often used in functional foods and beverages as colorants and
      nutraceuticals. However, these natural compounds may undergo chemical degradation
      during storage leading to color fading and loss of bioactivity. In particular,
      vitamin C (l-ascorbic acid) is known to accelerate anthocyanin degradation. In
      this study, the influence of various food-grade biopolymers on the physical and
      chemical stability of model beverages containing anthocyanin (0.025%), ascorbic
      acid (0 or 0.05%), and calcium salt (0 or 0.01%) was examined under accelerated
      conditions (40 degrees C for 7days). Four biopolymers (1%) were examined for
      their potential to inhibit anthocyanin degradation: native whey protein;
      denatured whey protein; citrus pectin; and beet pectin. The physical stability
      was determined by measuring changes in absorbance, color, and visual appearance.
      Solutions containing anthocyanin and calcium salt (0 or 0.01%) were stable
      throughout storage, while those with added ascorbic acid were the least stable.
      The addition of biopolymers, particularly heat denatured whey protein,
      significantly enhanced the stability of the anthocyanin during storage.
      Fluorescence quenching studies showed that the anthocyanin may have formed
      complexes with the whey protein through hydrogen bonding that resulted in their
      enhanced stability in the presence of ascorbic acid. This study provides
      information that may improve the stability of anthocyanins in food and beverage
      systems.

PMID- 28455062
TI  - Potential impact of biopolymers (epsilon-polylysine and/or pectin) on
      gastrointestinal fate of foods: In vitro study.
AB  - Food-grade biopolymers, such as proteins and polysaccharides, may impact the
      gastrointestinal fate of foods through various mechanisms. In this study, we
      examined the influence of epsilon-polylysine (an antimicrobial) and pectin (a
      thickening agent) on the behavior of a standard rodent diet (full-fat and fat
      free) in a simulated gastrointestinal tract that included mouth, stomach, and
      small intestine phases. Powdered biopolymers were incorporated into the standard
      diet in either individual or complexed form. The presence of the biopolymers
      altered the microstructure and charge characteristics of the gastrointestinal
      contents. In particular, the presence of pectin appeared to increase the rate and
      extent of lipid digestion, which may have been due to its ability to inhibit
      protein aggregation. Our results do not support the hypothesis that polylysine
      inhibits lipid digestion, as has been reported previously. Overall, the results
      of this study may be useful for interpreting animal feeding studies of the
      influence of biopolymers on the gastrointestinal fate of foods.

PMID- 28455063
TI  - Design of reduced-fat food emulsions: Manipulating microstructure and rheology
      through controlled aggregation of colloidal particles and biopolymers.
AB  - The objective of this study was to develop model reduced-calorie food emulsions
      with desirable textural and optical properties based on controlled aggregation of
      food-grade colloidal particles and biopolymers. The model food emulsion consisted
      of fat droplets (5wt.%), starch granules (4wt.%), and xanthan gum (0 to 0.02wt.%)
      under acidic conditions (pH3). The fat droplets were stabilized by a protein
      based emulsifier (whey protein isolate). Fat droplet aggregation was induced by
      adding anionic xanthan gum to promote bridging flocculation of the cationic
      protein-coated fat droplets. Thermal processing (95 degrees C) did not have a
      major impact on fat droplet aggregation, but it did promote starch granule
      swelling. The structural organization of the fat droplets could be regulated by
      altering xanthan levels. Relatively small droplet aggregates were formed at low
      xanthan concentrations that coated the starch granule surfaces. Conversely, large
      irregular shaped droplet aggregates were formed throughout the system at higher
      xanthan levels. The rheological and optical properties of the model emulsions
      could therefore be controlled by altering fat droplet organization. Addition of
      low levels of xanthan significantly increased the viscosity, yield stress, and
      complex modulus of the model food emulsions. However, high levels of xanthan led
      to the formation of large visible aggregates that would negatively impact on
      sensory quality. This study has important implications for the development of
      cost-effective and clean-label reduced-fat products with desirable quality
      attributes, such as dressings and sauces.

PMID- 28455064
TI  - Microbiological and chemical parameters during cassava based-substrate
      fermentation using potential starter cultures of lactic acid bacteria and yeast.
AB  - Traditional Brazilian indigenous fermented foods and beverages are potential
      sources of new food products that promote health, but they are still produced by
      natural fermentation. In the present work, Lactobacillus fermentum CCMA 0215
      isolated from the indigenous fermented cassava beverage yakupa was used as single
      or mixed starter culture with five different yeast strains (Torulaspora
      delbrueckii CCMA 0234 and CCMA 0235, Pichia caribbica CCMA 0198, and
      Saccharomyces cerevisiae CCMA 0232 and CCMA 0233) to ferment cassava.
      Fermentations using each yeast as single starter culture were also performed. The
      microbial population and metabolites produced during cassava fermentation were
      investigated. In all assays, the inoculated microorganisms fermented cassava,
      judged by lowering the pH from 6.0 to 4.0-5.0 within 24h. Lactic acid bacteria
      (LAB) and yeast population increased during fermentation. Lactic acid was the
      main organic acid produced, reaching a maximum value of 4.5g/L at 24h in the co
      culture with L. fermentum CCMA 0215 and T. delbrueckii CCMA 0234. Other organic
      acids, such as malic, tartaric, and succinic acids, were detected in low
      concentrations (less than 0.5g/L). Ethanol and glycerol were produced in all
      assays inoculated with yeasts (single and co-cultured with LAB), reaching the
      maximum concentration of approximately 2.3g/L and 0.6g/L, respectively. Twenty
      two volatile compounds were detected after 48h of fermentation, varying widely
      between single and co-cultures. The compounds 2-phenylethyl alcohol, 1-butanol, 3
      methyl (isoamyl alcohol), and acetoin were detected in single and co-cultures.
      This study demonstrated co-cultures of yeasts and LAB had the ability to improve
      the aroma profile of the final product and the safety of the product by lowering
      the pH.

PMID- 28455065
TI  - Green propolis modulates gut microbiota, reduces endotoxemia and expression of
      TLR4 pathway in mice fed a high-fat diet.
AB  - Due to the various beneficial effects attributed to propolis, which include anti
      inflammatory and anti-bacterial infection properties, the objective of the study
      was to evaluate the effect of propolis supplementation on the composition of the
      intestinal microbiota and its anti-inflammatory action. Forty male C57BL/6 mice
      were fed either a standard diet (control), a high-fat (HF) diet, or a high-fat
      diet supplemented with 0.2% crude propolis (HFP) for 2 or 5weeks prior to
      sacrifice. Blood samples were collected for the determination of
      lipopolysaccharide (LPS) and classical biochemical parameters. Expression of the
      TLR4 pathway in muscle, and DNA sequencing for the 16S rRNA of the gut microbiota
      were performed. The HF diet increased the proportion of the phylum Firmicutes and
      inflammatory biomarkers, while supplementation with propolis for five weeks
      rendered the microbiota profile nearly normal. Consistently with the above, the
      supplementation reduced levels of circulating LPS and down-regulated the TLR4
      pathway and inflammatory cytokine expressions in muscle. Moreover, propolis
      improved such biochemical parameters as serum triacylglycerols and glucose
      levels. The data suggest that propolis supplementation reduces inflammatory
      response and endotoxemia by preventing dysbiosis in mice challenged with a high
      fat diet.

PMID- 28455066
TI  - Comparative study on characteristics and in vitro fibril formation ability of
      acid and pepsin soluble collagen from the skin of catla (Catla catla) and rohu
      (Labeo rohita).
AB  - Catla (Catla catla) and Rohu (Labeo rohita) are the major carp fish produced by
      freshwater aquaculture in India. Processing of these carp fish generates
      potentially large quantities of by-products (waste) from non-edible fish parts by
      fish-processing factories and fish shops. The paper focuses on the extraction of
      the acid soluble collagen (ASC) and pepsin soluble collagen (PSC) from the skin
      of carp fish and subsequently their characteristics and in vitro fibril-forming
      ability. The extracted collagens are characterized as type I collagen based on
      the electrophoretic pattern. The denaturation temperature for all the collagens
      extracted was found to be 30.69-35.19 degrees C by differential scanning
      calorimetry (DSC) analysis. The extracted collagens exhibited higher solubility
      at low concentration of NaCl (0-0.4M). All the ASC and PSC displayed different
      degrees of fibril-forming abilities and the scanning electron microscopy (SEM)
      analysis confirmed their well-defined fibril morphologies. The degree of collagen
      fibril formation was significantly (p<=0.05) higher (78%) in rohu skin collagen
      than catla skin collagen (36%). In general, the characteristics of two carp skin
      collagens were unique as evidenced by the electrophoretic, DSC, SEM and fibril
      forming patterns. Overall, the results indicated the feasibility of using the
      carp skin as a good alternative source of realistic high-quality collagen.

PMID- 28455067
TI  - Effects of cooking and in vitro digestion of rice on phenolic profiles and
      antioxidant activity.
AB  - The aim of this study was to analyze the content and distribution of free and
      bound phenolic components and the oxygen radical absorbance capacity (ORAC)
      antioxidant activity of brown and polished rice after cooking and in vitro
      digestion. The results showed that cooking decreased the free and bound phenolic
      and flavonoid contents and ORAC values. Cooking decreased the total phenolic
      content of brown and polished rice by 47.9% and 71.0%, total flavonoid content by
      72.8% and 82.5%, and total ORAC values by 31.8% and 72.9%, respectively. After in
      vitro digestion, the total phenolic content, total flavonoid content, and total
      ORAC values had increased by 195.6%, 34.6% and 185.7%, respectively, in brown
      rice, and by 403.3%, 13.1% and 293.4% respectively, in polished rice, compared
      with the cooked samples. Seven individual phenolics (gallic, protocatechuic,
      chlorogenic, caffeic, syringic, coumaric, and ferulic acids) were detected in
      both free and bound forms. The results showed that the phytochemical content and
      its antioxidant activity after cooking will be underestimated if the bound
      fraction after in vitro digestion is not included in calculations. The results of
      this study show that cooking affects the phenolic content and antioxidant
      capacity of rice. However, the in vitro digestion process could actually improve
      the digestion and absorption of beneficial components of cooked rice at the
      intestinal level.

PMID- 28455068
TI  - The contribution of phenolic acids to the anti-inflammatory activity of
      mushrooms: Screening in phenolic extracts, individual parent molecules and
      synthesized glucuronated and methylated derivatives.
AB  - In the present study, the ethanolic extracts of fourteen edible mushrooms were
      investigated for their anti-inflammatory potential in LPS (lipopolysaccharide)
      activated RAW 264.7 macrophages. Furthermore the extracts were chemically
      characterized in terms of phenolic acids and related compounds. The identified
      molecules (p-hydroxybenzoic, p-coumaric and cinnamic acids) and their
      glucuronated and methylated derivatives obtained by chemical synthesis were also
      evaluated for the same bioactivity, in order to establish structure-activity
      relationships and to comprehend the effects of in vivo metabolism reactions in
      the activity of the compounds. The extracts of Pleurotus ostreatus, Macrolepiota
      procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti
      inflammatory potential (EC50 values 96+/-1 to 190+/-6MUg/mL), and also the
      highest concentration of cinnamic acid (656 to 156MUg/g), which was also the
      individual compound with the highest anti-inflammatory activity. The derivatives
      of p-coumaric acid revealed the strongest properties, specially the derivative
      methylated in the carboxylic group (CoA-M1) that exhibited similar activity to
      the one showed by dexamethasone used as anti-inflammatory standard; by contrast,
      the derivatives of p-hydroxybenzoic revealed the lowest inhibition of NO
      production. All in all, whereas the conjugation reactions change the chemical
      structure of phenolic acids and may increase or decrease their activity, the
      glucuronated and methylated derivatives of the studied compounds are still
      displaying anti-inflammatory activity.

PMID- 28455069
TI  - Effects of added Lactobacillus acidophilus and Bifidobacterium lactis probiotics
      on the quality characteristics of goat ricotta and their survival under simulated
      gastrointestinal conditions.
AB  - This study evaluated the effects of incorporating the probiotics Bifidobacterium
      animalis subsp. lactis Bb-12 (B. lactis) or Lactobacillus acidophilus La-05 (L.
      acidophilus) into goat ricotta on the technological, physicochemical, physical
      and sensory parameters of this product during refrigerated storage, as well as
      the protective effects of the goat ricotta on the survival of the tested
      probiotics during exposure to simulated gastrointestinal conditions.
      Incorporating the tested probiotics did not affect the yield or syneresis of the
      obtained goat ricotta. The counts of L. acidophilus and B. lactis during the
      chosen storage period were approximately 6 log CFU/g. The ricotta samples
      containing a probiotic strain presented smaller and greater amounts of lactose
      and lactic acid, respectively, and exhibited greater hardness and lower
      brightness after storage compared with the samples lacking a probiotic. No
      differences were observed in the fatty acid profiles of the goat ricotta
      containing or not containing a probiotic. All of the ricotta samples were
      described as a soft cheese with a homogeneous texture; however, the goat ricotta
      cheeses containing L. acidophilus or B. lactis were described as having a more
      acidic flavor. At the end of a challenge using experimental human digestive
      conditions, the counts of each of the tested probiotic strains were approximately
      6 log CFU/g if it had been incorporated into goat ricotta. These results
      demonstrated the feasibility of incorporating L. acidophilus or B. lactis into
      goat ricotta because these probiotics did not negatively affect the quality
      characteristics of this product and suggested that goat ricotta is an efficacious
      food matrix for maintaining the viability of these probiotics during storage and
      under the stressful conditions imposed by the human gastrointestinal tract.

PMID- 28455070
TI  - Hard-to-cook bean (Phaseolus vulgaris L.) proteins hydrolyzed by alcalase and
      bromelain produced bioactive peptide fractions that inhibit targets of type-2
      diabetes and oxidative stress.
AB  - The objective was to evaluate the effect of bioactive peptide fractions from de
      hulled hard-to-cook (HTC) bean on enzyme targets of type-2 diabetes and oxidative
      stress. Protein isolates from Pinto Durango and Negro 8025 beans were hydrolyzed
      (120min) with either alcalase(r) or bromelain and separated into five peptide
      fractions (<1, 1-3.5, 3.5-5, 5-10, and >10kDa) using an ultrafiltration membrane
      system. The <1kDa pinto Durango-bromelain fraction showed the best inhibition of
      alpha-amylase (49.9+/-1.4%), and the <1kDa pinto Durango-alcalase fraction
      inhibited both, alpha-glucosidase (76.4+/-0.5%), and dipeptidyl peptidase-IV (DPP
      IV, 55.3+/-1.6%). Peptides LLSL, QQEG and NEGEAH were present in the most potent
      fractions. Hydrolysates and peptide fractions showed antioxidant capacity (ORAC:
      159.6+/-2.9 to 932.6+/-1.1mmolTE/g) and nitric oxide inhibition (57.5+/-0.9 to
      68.3+/-4.2%). Hydrolysates and fractions <1 and 1-3kDa were able to increase
      glucose-stimulated insulin secretion from iNS-1E cells up to 57% compared to
      glucose control. Hydrolysates from HTC beans inhibited enzymes related to
      diabetes management, being the smallest peptides (<1kDa) the most potent. HTC
      bean could be a source of protein to produce bioactive peptides with potential
      antidiabetic properties.

PMID- 28455071
TI  - The nutraceutical response of two globe artichoke cultivars to contrasting NPK
      fertilizer regimes.
AB  - Globe artichoke contributes to the healthiness of the Mediterranean diet, but its
      nutraceutical value in response to its agronomy has not been investigated in any
      detail to date. Here, the effect of two contrasting fertilizer regimes (one
      balanced and the other excessive) on the sugar, ascorbic acid and total
      polyphenol content, the polyphenol profile and the antioxidant activity of the
      two cultivars 'Apollo' and 'Tema 2000' were monitored in plants grown in three
      locations in Sicily ('Landolina', 'Iannarello' and 'Zotto'), which contrasted for
      soil type. The balanced fertilizer regime favored the content of sucrose, inulin,
      ascorbic acid and polyphenols (in particular that of 1,5-di- and 5-O
      caffeoylquinic acid, along with apigenin 7-O-glucuronide). It was also more
      supportive of a high antioxidant activity. There was a pronounced cultivar and
      trial location effect, especially in terms of the accumulation of antioxidant
      compounds. Plants grown at 'Landolina' responded more strongly than at the other
      two locations to the fertilizer regime with respect to both ascorbic acid and
      total polyphenol content. The conclusion was that providing a balanced supply of
      nitrogen/phosphorus/potassium (NPK) via fertilizer application can enhance the
      nutraceutical value of globe artichoke, although the effect is modulated by both
      genetic factors and soil type.

PMID- 28455072
TI  - Impact of gas formation kinetics on dough development and bread quality.
AB  - The baking performance and gas retention capacity of wheat dough depends on
      production rate and total volume of CO2 during fermentation. This study aims to
      examine the effect of the CO2 formation kinetics and the gas volume fraction on
      the structural integrity of wheat dough and the resulting bread quality. The gas
      release characteristics were evaluated using a rheofermentometer with varied
      concentrations of compressed yeast and instant dry yeast (CY and IDY
      respectively). For this purpose, the maximum CO2 formation rate was calculated
      through the derivation of hydrostatic pressure curves measured in the
      rheofermentometer. For CY, the time when gas escapes the dough matrix (Tx, time
      of porosity) as well as the corresponding gas volume depended on the gas
      formation rate, whereas the gas retention capacity of wheat dough leavened with
      IDY was not affected by the CO2 formation rate. Although the dough leavened with
      IDY showed improved extensibility during fermentation, the specific bread volume
      was 21% below that of the samples leavened with CY. These results indicate that
      an increase in the maximum gas formation rate considerably affects the structural
      integrity of the dough matrix. Because of the reduction of the loaf volume, the
      effect is reinforced by the application of IDY.

PMID- 28455073
TI  - Physical stability of l-ascorbic acid amorphous solid dispersions in different
      polymers: A study of polymer crystallization inhibitor properties.
AB  - The effects of different polymer types on inhibiting the crystallization of
      ascorbic acid (VitC) from amorphous solid dispersions at various temperatures and
      relative humidities (RHs) were studied. Polymer properties (ability to form
      hydrogen bonds with VitC, hygroscopicity, and glass transition temperature (Tg))
      were correlated to their crystallization inhibitor performance. Solid dispersions
      of VitC with different pectins, polyvinylpyrrolidone (PVP), and polyacrylic acid
      (PAA) were formed from lyophilized solutions. Crystallinity, VitC-polymer
      interactions, hygroscopicity, and Tg were determined using X-ray powder
      diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), moisture
      sorption isotherm, and differential scanning calorimetry (DSC) methods,
      respectively. XRPD amorphous VitC could not be formed by lyophilization in the
      absence of a polymer, nor in PAA dispersions, but could be formed in pectin and
      PVP dispersions. The VitC-pectin and PVP dispersions remained amorphous when
      stored at low RHs, but some crystallization occurred within one week at high RHs.
      Evidence of hydrogen bonding between VitC and both pectins and PVP, but not PAA,
      was found in FTIR spectra, and correlated better with physical stability than the
      Tg. The hygroscopicity of the polymer also influenced the stability of the
      amorphous VitC solid dispersions. A ranking of the polymer crystallization
      inhibitor properties was: PVP>pectin with lower degree of esterification
      (DE)>pectin with higher DE >>PAA.

PMID- 28455075
TI  - Agar dilution minimum inhibitory concentrations under-represent oritavancin in
      vitro activity against staphylococci and enterococci.

PMID- 28455074
TI  - Management strategies and possible risk factors for ventricular septal defects
      after transcatheter aortic valve replacement: Case series from a single center
      and review of literature.
AB  - Development of membranous ventricular septal defects (VSD) is a rare complication
      of transcatheter aortic valve replacements (TAVR), and is recognized using
      intraoperative and postoperative imaging. We present two cases of this rare but
      serious complication; one was successfully managed conservatively and the other
      with valve-in-valve therapy. Management strategies for post-TAVR VSDs varies, but
      should be individualized to the clinical scenario. We performed a literature
      search and sought to identify various risk factors which may predispose patients
      to the development of VSD after TAVR.

PMID- 28455076
TI  - Diversity of blaOXA-51 variants and its clonal complexes in multidrug-resistant
      Acinetobacter baumannii strains in patients with ventilator-associated pneumonia.

PMID- 28455077
TI  - Prescription of antibiotics for pulpal and periapical pathology among dentists in
      southern Saudi Arabia.
AB  - OBJECTIVES: Few dental conditions require treatment with antibiotics, yet
      dentists account for 7% of antimicrobial prescribing. In light of the emerging
      global problem of antibiotic resistance, this fact is problematic. Little is
      known about the antibiotic prescribing practices of dentists in Saudi Arabia.
      This study therefore aimed to investigate the attitudes of dentists in Saudi
      Arabia towards the prescription of antibiotics for pulpal and periapical
      pathology. METHODS: This was a cross-sectional study involving an online
      questionnaire on antibiotic prescribing practices. A total of 195 dentists in
      three areas of southern Saudi Arabia (Najran, Gizan and Asser) completed the
      survey. RESULTS: No significant differences in prescribing habits were found
      among respondents according to age, sex, level of education or time in endodontic
      practice. The percentage of respondents who reported that they would prescribe
      antibiotics for five endodontic conditions not requiring antibiotic treatment
      ranged from 8.1% to 28.1%. Most respondents (81.9%) would correctly prescribe
      antibiotics for a necrotic pulp with acute apical periodontitis and swelling;
      this result was consistent with previous studies. Reported antibiotic usage among
      the surveyed dentists was quite high. CONCLUSIONS: Relatively high antibiotic use
      suggests a need to educate both dentists and patients about restricting the use
      of antibiotics to cases of severe infection and when indicated. More educational
      initiatives to rationalise the use of antibiotics in dental practice are needed
      to avoid further contributing to antibiotic resistance.

PMID- 28455078
TI  - Sexual function in infertile women with polycystic ovary syndrome and unexplained
      infertility.
AB  - BACKGROUND: While female sexual dysfunction is a frequent occurrence,
      characteristics in infertile women are not well delineated. Furthermore, the
      impact of infertility etiology on the characteristics in women with differing
      androgen levels observed in women with polycystic ovary syndrome and unexplained
      infertility has not been assessed. OBJECTIVE: The objective of the study was to
      determine the characteristics of sexual dysfunction in women with polycystic
      ovary syndrome and unexplained infertility. STUDY DESIGN: A secondary data
      analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child
      Health and Human Development Cooperative Reproductive Medicine Networks clinical
      trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of
      Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols
      assessed female sexual function using the Female Sexual Function Inventory and
      the Female Sexual Distress Scale. RESULTS: Women with polycystic ovary syndrome
      had higher weight and body mass index than women with unexplained infertility
      (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum
      score, and acne score; each P < .001), and hormonal (testosterone, free
      testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen
      excess. Sexual function scores, as assessed by the Female Sexual Function
      Inventory, were nearly identical. The Female Sexual Distress Scale total score
      was higher in women with polycystic ovary syndrome. The mean Female Sexual
      Function Inventory total score increased slightly as the free androgen index
      increased, mainly as a result of the desire subscore. This association was more
      pronounced in the women with unexplained infertility. CONCLUSION: Reproductive
      age women with infertility associated with polycystic ovary syndrome and
      unexplained infertility, despite phenotypic and biochemical differences in
      androgenic manifestations, do not manifest clinically significant differences in
      sexual function.

PMID- 28455079
TI  - Impact of USPSTF recommendations for aspirin for prevention of recurrent
      preeclampsia.
AB  - BACKGROUND: The US Preventive Services Task Force recommends low-dose aspirin for
      the prevention of preeclampsia among women at high risk for primary occurrence or
      recurrence of disease. Recommendations for the use of aspirin for preeclampsia
      prevention were issued by the US Preventive Services Task Force in September
      2014. OBJECTIVES: The objective of the study was to evaluate the incidence of
      recurrent preeclampsia in our cohort before and after the US Preventive Services
      Task Force recommendation for aspirin for preeclampsia prevention. STUDY DESIGN:
      This was a retrospective cohort study designed to evaluate the rates of recurrent
      preeclampsia among women with a history of preeclampsia. We utilized a 2
      hospital, single academic institution database from August 2011 through June
      2016. We excluded multiple gestations and included only the first delivery for
      women with multiple deliveries during the study period. The cohort of women with
      a history of preeclampsia were divided into 2 groups, before and after the
      release of the US Preventive Services Task Force 2014 recommendations. Potential
      confounders were accounted for in multivariate analyses, and relative risk and
      adjusted relative risk were calculated. RESULTS: A total of 17,256 deliveries
      occurred during the study period. A total of 417 women had a documented history
      of prior preeclampsia: 284 women before and 133 women after the US Preventive
      Services Task Force recommendation. Comparing the before and after groups, the
      proportion of Hispanic women in the after group was lower and the method of
      payment differed between the groups (P <.0001). The prevalence of type 1 diabetes
      was increased in the after period, but overall rates of pregestational diabetes
      were similar (6.3% before vs 5.3% after [P > .05]). Risk factors for recurrent
      preeclampsia included maternal age >35 years (relative risk, 1.83; 95% confidence
      interval, 1.34-2.48), Medicaid insurance (relative risk, 2.08; 95% confidence
      interval, 1.15-3.78), type 2 diabetes (relative risk, 2.13; 95% confidence
      interval, 1.37-3.33), and chronic hypertension (relative risk, 1.96; 95%
      confidence interval, 1.44-2.66). The risk of recurrent preeclampsia was decreased
      by 30% in the after group (adjusted relative risk, 0.70; 95% confidence interval,
      0.52-0.95). CONCLUSION: Rates of recurrent preeclampsia among women with a
      history of preeclampsia decreased by 30% after release of the US Preventive
      Services Task Force recommendation for aspirin for preeclampsia prevention.
      Future prospective studies should include direct measures of aspirin compliance,
      gestational age at initiation, and explore the influence of race and ethnicity on
      the efficacy of this primary prevention.

PMID- 28455080
TI  - The maternal childbirth experience more than a decade after delivery.
AB  - BACKGROUND: Maternal satisfaction with the birth experience is multidimensional
      and influenced by many factors, including mode of delivery. To date, few studies
      have investigated maternal satisfaction outside of the immediate postpartum
      period. OBJECTIVE: This study investigated whether differences in satisfaction
      based on mode of delivery are observed more than a decade after delivery. STUDY
      DESIGN: This was a planned, supplementary analysis of data collected for the
      Mothers' Outcomes after Delivery study, a longitudinal cohort study of pelvic
      floor disorders in parous women and their association with mode of delivery.
      Obstetric and demographic data were obtained through patient surveys and
      obstetrical chart review. Maternal satisfaction with childbirth experience was
      assessed via the Salmon questionnaire, administered to Mothers' Outcomes after
      Delivery study participants >10 years from their first delivery. This validated
      questionnaire yields 3 scores: fulfillment, distress, and difficulty. These 3
      scores were compared by mode of delivery (cesarean prior to labor, cesarean
      during labor, spontaneous vaginal delivery, and operative vaginal delivery). In
      addition, the impact of race, age, education level, parity, episiotomy, labor
      induction, and duration of second stage of labor on maternal satisfaction were
      examined. RESULTS: Among 576 women, 10.1-17.5 years from delivery, significant
      differences in satisfaction scores were noted by delivery mode. Salmon scale
      scores differed between women delivering by cesarean and those delivering
      vaginally: women delivering vaginally reported greater fulfillment (0.40 [-0.37
      to 0.92] vs 0.15 [-0.88 to 0.66], P < .001) and less distress (-0.34 [-0.88 to
      0.38] vs 0.20 [-0.70 to 0.93], P < .001) than those who delivered by cesarean.
      Women who delivered by cesarean prior to labor reported the greatest median
      fulfillment scores and the lowest median difficulty scores. Median distress
      scores were lowest among those who delivered by spontaneous vaginal birth. Among
      women who underwent cesarean delivery, labor induction and prolonged second stage
      were associated with higher difficulty scores. These factors did not affect
      satisfaction scores among women who delivered vaginally. Among women who
      delivered vaginally, operative vaginal delivery was associated with less
      favorable scores across all 3 scores. CONCLUSION: Maternal satisfaction with
      childbirth is influenced by mode of delivery. The birth experience leaves an
      impression on women more than a decade after delivery.

PMID- 28455081
TI  - Optimizing postpartum care for the patient with gestational diabetes mellitus.
AB  - Gestational diabetes mellitus poses well-established risks to both the mother and
      infant. As >50% of women with gestational diabetes mellitus will develop type 2
      diabetes mellitus in their lifetime, performing postpartum oral glucose tolerance
      testing is paramount to initiation of appropriate lifestyle interventions and
      pharmacologic therapy. Nonetheless, test completion among women with gestational
      diabetes mellitus is estimated to be <50%, with particularly low rates in Latina
      patients, as well as patients with public insurance, low education levels, and
      low health literacy. Data suggest our current health services infrastructure
      loses patients in the postpartum gap between pregnancy-focused care and primary
      care. Previous studies have suggested strategies to promote oral glucose
      tolerance testing completion to identify type 2 diabetes mellitus. Based on
      existing evidence, we propose best practices for the postpartum care of women
      with gestational diabetes mellitus: (1) enhanced patient support for identifying
      long-term health care providers, (2) patient-centered medical home utilization
      when possible, (3) patient and provider test reminders, and (4) formalized
      obstetrician-primary care provider hand offs using the Situation Background
      Assessment Recommendation (SBAR) mnemonic. These strategies deserve future
      investigation to solidify a multilevel approach for identifying and preventing
      the continuum of diabetes.

PMID- 28455082
TI  - Ovarian reserve following cesarean section with salpingectomy vs tubal ligation:
      a randomized trial.
AB  - BACKGROUND: Epithelial ovarian cancer is assumed to derive from the fallopian
      tube. Salpingectomy has been previously demonstrated to reduce the risk of
      ovarian cancer, and may be used as a means of sterilization. OBJECTIVE: We aimed
      to compare short-term ovarian reserve and operative complications in cases of
      salpingectomy and tubal ligation during cesarean section. STUDY DESIGN: Study
      patients who underwent elective cesarean section at our institution and requested
      sterilization were randomized to bilateral salpingectomy or tubal ligation. Prior
      to surgery, blood samples were obtained for antimullerian hormone. Surgical
      course was noted, including overall time, complications, and postoperative
      hemoglobin. Repeat antimullerian hormone samples were obtained from patients 6-8
      weeks following surgery. RESULTS: In all, 46 patients were recruited for
      participation, of whom 33 completed a follow-up visit, and for whom repeat
      antimullerian hormone levels were available. Patients in the salpingectomy group
      were slightly older (37.0 +/- 3.9 vs 34.3 +/- 4.1 years, P = .02). No differences
      were noted in patient parity, body mass index, or gestational age between the
      groups. Pregnancy and postdelivery antimullerian hormone levels were not
      significantly different between the groups, with an average increase of 0.58 +/-
      0.98 vs 0.39 +/- 0.41 ng/mL in the salpingectomy and tubal ligation groups,
      respectively (P = .45). Surgeries including salpingectomy were longer by an
      average 13 minutes (66.0 +/- 20.5 vs 52.3 +/- 15.8 minutes, P = .01). No
      difference was demonstrated between the groups regarding surgical complications
      and postoperative hemoglobin decrease. CONCLUSION: Sterilization by salpingectomy
      appears to be as safe as tubal ligation regarding operative complications and
      subsequent ovarian reserve. As salpingectomy offers the advantage of cancer risk
      reduction, it may be offered in the settings of elective preplanned surgeries.

PMID- 28455083
TI  - Ureteral stone diagnosed with 3-dimensional transvaginal ultrasonography.

PMID- 28455084
TI  - Recipient umbilical artery elongation (redundancy) in twin-twin transfusion
      syndrome.
AB  - BACKGROUND: Chronic hypertension in adults causes arterial lengthening in major
      arteries, but the effects of early fetal hypertension on the twin-twin
      transfusion syndrome recipient's vascular architecture remains unknown.
      OBJECTIVE: We hypothesize that arterial cord redundancy is related to recipient
      hypertension and subsequent heart failure. Our objectives were to: (1) establish
      a 3-dimensional color Doppler ultrasound method of measuring umbilical arterial
      length relative to its corresponding venous segment in the umbilical cord using
      artery vein angle; (2) compare recipient artery vein angle to gestational age
      matched controls; and (3) test the association of artery vein angle with
      recipient heart failure. STUDY DESIGN: We compared 3 groups prospectively: twin
      twin transfusion syndrome pregnancies undergoing fetoscopic laser surgery
      (preoperatively) and 2 groups of gestational age-matched controls: uncomplicated
      monochorionic-diamniotic twin pregnancies and healthy singletons. Using a 3
      dimensional color-Doppler volume image of 5 cm of cord near the placental
      insertion, we traced the umbilical artery and vein producing umbilical
      artery:vein length, (artery vein index) and measured the artery vein angle
      between umbilical artery and vein. Correlation of artery vein angle to twin-twin
      transfusion syndrome stage, maximum vertical pocket, umbilical arterial indices,
      ductus venosus Doppler, and brain natriuretic peptide were performed. We used
      pulsed-wave and tissue Doppler to measure tissue Doppler velocities and indexed
      cardiac output and correlated these with artery vein angle. Comparative
      statistics, including multivariable linear regression, examined the relationship
      between umbilical arterial Doppler indices and artery vein angle. RESULTS: Artery
      vein angle and artery vein index correlated significantly (R2, 0.86; P < .0001),
      hence, artery vein angle was used for analysis. Mean artery vein angle was 33.1
      +/- 31.5 degrees in recipients (n = 44), 9.5 +/- 6 degrees in monochorionic
      diamniotic (n = 11; 22 fetuses), and 8.9 +/- 8.3 degrees in singleton controls (n
      = 16) (P < .001). An artery vein angle >=26 degrees (>95th percentile for
      controls) was measured in 52% recipients. Artery vein angle was higher in twin
      twin transfusion syndrome stage 3R vs 1 (P = .001). Artery vein angle increased
      with increasing umbilical arterial pulsatility index (P < .001), and decreased
      with increasing resistance index (P = .02) after adjusting for gestational age.
      Interrater agreements to categorize abnormal artery vein angle values was 95% (P
      < .001). Abnormal ductus venosus Doppler and elevated recipient amniotic fluid N
      terminal pro-brain natriuretic peptide/protein levels correlated significantly
      with artery vein angle. Abnormal artery vein angles were associated with
      decreased indexed cardiac output, lower tissue Doppler velocities, higher right
      sided Tei indices, and severe tricuspid regurgitation. CONCLUSION: Umbilical
      arterial lengthening occurs in 52% of recipients and is associated with abnormal
      Doppler flows, low systolic tissue Doppler velocities, reduced cardiac output,
      and elevated markers of cardiac failure. This may reflect chronicity and severity
      of hypertension in the recipient fetus. Further research is needed to explore the
      mechanisms of elongation and long-term implications.

PMID- 28455085
TI  - Randomized controlled trial of intravenous acetaminophen for postcesarean
      delivery pain control.
AB  - BACKGROUND: Cesarean delivery is a common surgery in the United States, with 1.3
      million performed during 2009.1 Obstetricians must balance the growing concern
      with opioid abuse, dependence, and side effects with optimal postoperative pain
      control. Intravenous acetaminophen may represent an additional method to decrease
      the reliance on opioid medications and improve postoperative pain following
      cesarean delivery. OBJECTIVE: The objective of the study was to determine whether
      the administration of intravenous acetaminophen following routine scheduled
      cesarean delivery would decrease the need for narcotic medications to control
      postoperative pain. STUDY DESIGN: This was an institutional review board
      approved, double-blind, placebo-controlled, randomized trial, registered on
      clinicaltrials.gov (number 02046382). Women scheduled to undergo cesarean
      delivery with regional anesthesia at term were recruited. All perioperative and
      postpartum care was standardized via study order sets. Study patients were given
      all medications in a standardized manner receiving either acetaminophen 1000 mg
      intravenously or 100 mL saline (placebo) every 8 hours for 48 hours for a total
      of 6 doses. The pharmacy prepared intravenous acetaminophen and saline in
      identical administration bags labeled study drug to ensure blinding. The initial
      dose of study drug was given within 60 minutes of skin incision. Quantity of
      breakthrough and scheduled analgesic medications and self-reported pain levels on
      the Faces Pain Scale (0-10) before and after study drug administration were
      collected. Patient demographics were extracted from the chart. Power calculation
      determined that 45 patients per arm were required to detect a 30% reduction in
      postcesarean narcotic requirement with 80% power and a significance level of P =
      .05. RESULTS: A total of 133 patients were consented for the study. Twenty-nine
      were excluded and 104 patients completed the study: 57 received intravenous
      acetaminophen and 47 received placebo. There were no differences in baseline
      demographic characteristics including patient age, body mass index, gravidity,
      parity, race, comorbidities, or number of prior cesarean deliveries. There were
      no differences between groups in estimated blood loss or length of stay. The
      total amount of oral narcotic medications consumed by patients receiving
      intravenous acetaminophen was significantly reduced when compared with the
      placebo group (47 mg vs 65 mg of oxycodone; P = .034). The total amount of
      ibuprofen used between groups was not different. There was no difference in pain
      scores between groups before and after study dose administration. There was no
      significant difference in narcotic side effects (nausea/emesis, respiratory
      depression, constipation) in either study arm. CONCLUSION: Intravenous
      acetaminophen in the postoperative period following cesarean delivery resulted in
      a significant decrease in oral narcotic consumption for pain control.

PMID- 28455088
TI  - Emergency Department Registered Nurses' conceptualisation of recovery for people
      experiencing mental illness.
AB  - BACKGROUND: The Emergency Department (ED) is an integral link to both mental
      health inpatient and community services and people experiencing mental health
      crisis often access mental healthcare through EDs. As such EDs have a significant
      role in enabling optimal transition of mental health consumers between services.
      The notion of recovery as it is understood by people who experience mental
      illness, and the delivery of recovery oriented mental healthcare services, are
      now embedded in mental health service provision in Australia and documented in
      policy. However, disparity exists in the meaning of recovery with the term
      meaning different things depending on the lens through which the concept is
      viewed. This research aimed to understand how Registered Nurses (RNs) working in
      the ED conceptualise recovery for people experiencing mental illness. METHODS:
      Using a phenomenographic approach, individual semi structured interviews were
      undertaken with 14 RNs working in Australian EDs. A seven stage cycle of data
      analysis resulted in the identification of six categories of description.
      RESULTS: The categories were - recovery not occurring; seeking help from the ED;
      getting through the acute mental health crisis; referral to other areas of mental
      healthcare; implementing strategies for ongoing care, and living in the
      community. CONCLUSIONS: Findings conclude that ED RNs have limited cognisance of
      the meaning of recovery as it is understood by people with lived experience of
      mental illness. Their conceptualisation of recovery for mental health consumers
      predominantly remains bound to the dominant medical notion of recovery.

PMID- 28455087
TI  - Assessing the potential impact of extending antenatal steroids to the late
      preterm period.
AB  - BACKGROUND: In 2016, guidance statements were issued by the Society for Maternal
      Fetal Medicine and the American Congress of Obstetricians and Gynecologists about
      extending antenatal steroid use to selected late preterm singleton pregnancies.
      OBJECTIVE: We sought to review antenatal steroid use prior to the 2016 guidance
      statements and assess the potential impact of these. STUDY DESIGN: This cohort
      study used chart-abstracted data from singleton deliveries from Jan. 1, 2012,
      through March 31, 2016, at 12 centers participating in the Obstetrics Clinical
      Outcomes Assessment Program, a quality initiative in Washington State.
      Pregnancies with missing gestation at delivery, fetal anomalies, or antepartum
      demise were excluded. Antenatal steroid use prior to the 2016 guidance was
      evaluated based on the percentage of early preterm deliveries (23+0-33+6 weeks)
      and the percentage of all pregnancies that received antenatal steroids. Newborn
      complication rates were calculated for late preterm deliveries (34+0+0-36+6
      weeks), grouped by whether they would be potentially eligible or ineligible for
      antenatal steroids based on the 2016 guidance statements. RESULTS: The
      opportunity for antenatal steroids was missed in 21.8% (226/1034) of early
      preterm deliveries and of all those who received antenatal steroids, 32.2%
      (614/1908) delivered at term. Of preterm deliveries, 74% (n = 2942) were in the
      late preterm period. In all, 80% (n = 2363) of late preterm deliveries were
      potentially eligible for antenatal steroids and 60% of these (n = 1411) delivered
      at 36 weeks. The rate of respiratory complications in newborns delivering at 34
      and 35 weeks was higher in the group potentially eligible for late preterm
      antenatal steroids compared to those in the ineligible group. Of those delivering
      at 36 weeks, no differences were detected in prevalence of respiratory
      complications by potential eligibility for antenatal steroids; however, compared
      with the ineligible group, those potentially eligible had a lower risk of
      neonatal intensive care unit admission (P < .001). More than two thirds (69%;
      171/248) of newborn respiratory complications among late preterm deliveries
      potentially eligible for antenatal steroids occurred in those delivering at 34-35
      weeks. The highest rate of respiratory complications was in those ineligible for
      antenatal steroids due to prepregnancy diabetes or chorioamnionitis, regardless
      of gestational age at delivery. CONCLUSION: Careful consideration of which
      pregnancies should receive late preterm antenatal steroids and how to identify
      these pregnancies is important to optimize benefits and mitigate potential risks
      of this intervention.

PMID- 28455086
TI  - Adverse pregnancy, birth, and infant outcomes in twins: effects of maternal
      fertility status and infant gender combinations; the Massachusetts Outcomes Study
      of Assisted Reproductive Technology.
AB  - BACKGROUND: It is unknown whether the risk of adverse outcomes in twin
      pregnancies among subfertile women, conceived with and without in vitro
      fertilization, differs from those conceived spontaneously. OBJECTIVE: We sought
      to evaluate the effects of fertility status on adverse perinatal outcomes in twin
      pregnancies on a population basis. STUDY DESIGN: All twin live births of >=22
      weeks' gestation and >=350 g birthweight to Massachusetts resident women in 2004
      through 2010 were linked to hospital discharge records, vital records, and in
      vitro fertilization cycles. Women were categorized by their fertility status as
      in vitro fertilization, subfertile, or fertile, and by twin pair genders (all,
      like, unlike). Women whose births linked to in vitro fertilization cycles were
      classified as in vitro fertilization; those with indicators of subfertility but
      without in vitro fertilization treatment were classified as subfertile; all
      others were classified as fertile. Risks of 6 adverse pregnancy outcomes
      (gestational diabetes, pregnancy hypertension, uterine bleeding, placental
      complications [placenta abruptio, placenta previa, and vasa previa], prenatal
      hospitalizations, and primary cesarean) and 9 adverse infant outcomes (very low
      birthweight, low birthweight, small-for-gestation birthweight, large-for
      gestation birthweight, very preterm [<32 weeks], preterm, birth defects, neonatal
      death, and infant death) were modeled by fertility status with the fertile group
      as reference, using multivariate log binomial regression and reported as adjusted
      relative risk ratios and 95% confidence intervals. RESULTS: The study population
      included 10,352 women with twin pregnancies (6090 fertile, 724 subfertile, and
      3538 in vitro fertilization). Among all twins, the risks for all 6 adverse
      pregnancy outcomes were significantly increased for the subfertile and in vitro
      fertilization groups, with highest risks for uterine bleeding (adjusted relative
      risk ratios, 1.92 and 2.58, respectively) and placental complications (adjusted
      relative risk ratios, 2.07 and 1.83, respectively). Among all twins, the risks
      for those born to subfertile women were significantly increased for very preterm
      birth and neonatal and infant death (adjusted relative risk ratios, 1.36, 1.89,
      and 1.87, respectively). Risks were significantly increased among in vitro
      fertilization twins for very preterm birth, preterm birth, and birth defects
      (adjusted relative risk ratios, 1.28, 1.07, and 1.26, respectively). CONCLUSION:
      Risks of all maternal and most infant adverse outcomes were increased for
      subfertile and in vitro fertilization twins. Among all twins, the highest risks
      were for uterine bleeding and placental complications for the subfertile and in
      vitro fertilization groups, and neonatal and infant death in the subfertile
      group. These findings provide further evidence supporting single embryo transfer
      and more cautious use of ovulation induction.

PMID- 28455090
TI  - Parkour injuries presenting to United States emergency departments, 2009-2015.
AB  - BACKGROUND: Few studies have examined injuries resulting from practicing parkour.
      The current study provides details on more parkour-related emergency department
      visits than existed in the combined research literature. METHODS: Cross-sectional
      data from the U.S. Consumer Product Safety Commission's National Electronic
      Injury Surveillance System were used to examine parkour-related injuries
      presenting to U.S. emergency departments over a seven year period. RESULTS: Most
      parkour injuries were reportedly caused by landing or from striking objects.
      Common diagnoses included fractures, sprains/strains, abrasions/contusions, and
      lacerations. More than half of reported injuries (57.7%) affected the patients'
      extremities. In this data, there appears to be a trend of increasing parkour
      injuries over time. Patients as young as 8years old have presented to emergency
      departments with parkour-related injuries in recent years. CONCLUSIONS: Given the
      relatively severe injuries obtained by youth participants, more research is
      needed to guide injury prevention efforts. Understanding the nature of parkour
      related injuries may help inform prevention efforts. However, more systematic
      monitoring of participation in parkour and related injuries is needed.

PMID- 28455091
TI  - Differences in test ordering between nurse practitioners and attending emergency
      physicians when acting as Provider in Triage.
AB  - STUDY OBJECTIVES: To compare diagnostic test ordering practices of NPs with those
      of physicians in the role of Provider in Triage (PIT). METHODS: This was a
      secondary analysis of data from a prospective RCT of waiting room diagnostic
      testing, where 770 patients had diagnostic studies ordered from the waiting room.
      The primary outcome was the number of test categories ordered by provider type.
      Other outcomes included total tests ordered by the end of ED stay, and time in an
      ED bed. We compared variables between groups using t-test and chi-square,
      constructed logistic regression models for individual test categories, and
      univariate and multivariate negative binomial models. RESULTS: Physicians ordered
      significantly more diagnostic test categories than NPs (1.75 vs. 1.54, p<0.001).
      By the end of their ED stay, there was no significant difference in total test
      categories ordered between provider type: physician 2.67 vs. NP 2.53 (p=0.08),
      using a nonbinomial model, incidence rate ratio (IRR) 1.07 (0.98-1.17). Patient
      time in an ED bed was not significantly different between physicians and NPs (NP
      244min, SD=133, Physicians 248min, SD=152) difference 4min (-24.3-16.1) p=0.688.
      CONCLUSION: NPs in the PIT role ordered slightly less diagnostic tests than
      attending physicians. This slight difference did not affect time spent in an ED
      bed. By the end of the ED stay, there was no significant difference in total test
      categories ordered between provider types. PIT staffing with NPs does not appear
      to be associated with excess test ordering or prolonged ED patient stays.

PMID- 28455092
TI  - Use of 3D transabdominal ultrasound imaging for treatment planning in cervical
      cancer brachytherapy: Comparison to magnetic resonance and computed tomography.
AB  - PURPOSE: To evaluate if the addition of 3D transabdominal ultrasound (3DTAUS)
      imaging to computed tomography (CT) can improve treatment planning in 3D adaptive
      brachytherapy when compared with CT-based planning alone, resulting in treatment
      plans closer to the ones obtained using magnetic resonance imaging (MRI)-based
      planning. METHODS AND MATERIALS: Five patients with cervical cancer undergoing
      brachytherapy underwent three imaging modalities: MRI, CT, and CT-3DTAUS. Volumes
      were delineated by a radiation oncologist and treatment plans were optimized on
      each imaging modality. To compare treatment plans, the dwell times optimized on
      MRI were transferred on CT and CT-3DTAUS images and dose parameters were reported
      on volumes of the receiving imaging modality. The plans optimized on CT and CT
      3DTAUS were also copied and evaluated on MRI images. RESULTS: Treatment plans
      optimized and evaluated on the same imaging modalities were clinically acceptable
      but statistically different (p < 0.05) from one another. MR-based plans had the
      highest target coverage (98%) and CT-based plans the lowest (93%). For all
      treatment plans evaluated on MRI, the target coverage was equivalent. However, a
      decrease in target coverage (V100) was observed when MR-based plans were applied
      on CT-3DTAUS (6%) and CT (13%) with p < 0.05. An increase in the rectum/sigmoid
      dose (D2cc) was observed with both CT-3DTAUS-based (0.6 Gy) and CT-based planning
      (1 Gy) when compared with MR-based plans, whereas bladder dose stayed similar.
      CONCLUSIONS: When compared with CT-based planning, the addition of 3DTAUS to CT
      results in treatment plans closer to MR-based planning. Its use reduces the high
      risk clinical target volume overestimation typically observed on CT, improving
      coverage of the target volume while reducing dose to the organs at risk.

PMID- 28455089
TI  - A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies.
AB  - There are currently no disease-modifying therapies for the treatment of
      tauopathies, a group of progressive neurodegenerative disorders that are
      pathologically defined by the presence of tau protein aggregates in the brain.
      Current challenges for the treatment of tauopathies include the inability to
      diagnose early and to confidently discriminate between distinct tauopathies in
      patients, alongside an incomplete understanding of the cellular mechanisms
      involved in pathogenic tau-induced neuronal death and dysfunction. In this
      review, we describe current diagnostic and therapeutic strategies, known drivers
      of pathogenic tau formation, recent contributions to our current mechanistic
      understanding of how pathogenic tau induces neuronal death, and potential
      diagnostic and therapeutic approaches.

PMID- 28455093
TI  - [Giant mesocolic cystic lymphangioma: A treacherous prenatal presentation. Case
      report].
AB  - Cystic lymphangiomas are usually located in the neck region. Less frequently,
      they can be found in the abdomen. In those cases, pre- and neonatal diagnosis is
      extremely difficult. We report on the case of a giant mesocolic cystic
      lymphangioma, diagnosed at birth, in a child who had been monitored during the
      prenatal period for what was believed to be a digestive dilatation. The
      progression was marked by excellent tolerance despite a complete lack of
      regression in the first 10 months of life. The authors discuss the prenatal signs
      that should suggest this diagnosis and an MRI, as well as management during the
      1st year of life.

PMID- 28455094
TI  - Layer-by-Layer polyelectrolyte assemblies for encapsulation and release of active
      compounds.
AB  - Soft assemblies obtained following the Layer-by-Layer (LbL) approach are
      accounted among the most interesting systems for designing biomaterials and drug
      delivery platforms. This is due to the extraordinary versatility and flexibility
      offered by the LbL method, allowing for the fabrication of supramolecular
      multifunctional materials using a wide range of building blocks through different
      types of interactions (electrostatic, hydrogen bonds, acid-base or coordination
      interactions, or even covalent bonds). This provides the bases for the building
      of materials with different sizes, shapes, compositions and morphologies,
      gathering important possibilities for tuning and controlling the physico-chemical
      properties of the assembled materials with precision in the nanometer scale, and
      consequently creating important perspective for the application of these
      multifunctional materials as cargo systems in many areas of technological
      interest. This review studies different physico - chemical aspects associated
      with the assembly of supramolecular materials by the LbL method, paying special
      attention to the description of these aspects playing a central role in the
      application of these materials as cargo platforms for encapsulation and release
      of active compounds.

PMID- 28455095
TI  - Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100
      Chinese patients with congenital hypothyroidism and athyreosis.
AB  - BACKGROUND: The abnormal expression of certain transcription factors (NKX2.1,
      FOXE1, NKX2.5, and PAX8) and thyroid stimulating hormone receptor (TSHR) genes
      has been associated with athyreosis, which is a form of thyroid dysgenesis (TD).
      We aimed to identify candidate gene mutations in CH patients with athyreosis and
      to establish the genotype-phenotype correlations in a Chinese population.
      METHODS: The exons and flanking sequences of NKX2.1, FOXE1, NKX2.5, PAX8, and
      TSHR were screened by next-generation sequencing and further confirmed by direct
      Sanger sequencing. The mutation frequencies were calculated and compared against
      databases. The relationship between genotype and phenotype was also determined.
      RESULTS: Seven variants were detected in TSHR-p.P52T, p.G132R, p.M164K, p.R450H,
      p.C700E, p.A522V, and p.R528S. The p. G132R, p. M164K and p. R528S variants were
      first identified in public databases. Five variants (p.G44D, p.G360V, p.R401Q,
      p.L418I, and p.E453Q) were found in NKX2.1 and one variant (p.P243T) was detected
      in FOXE1. In addition, one variant (p.N291I) was found in NKX2.5 and two variants
      (p.A355V and c.-26G>A) were detected in PAX8. CONCLUSIONS: Our study indicated
      that TSHR mutations have phenotypic variability and has further expanded the
      mutation spectrum of TSHR. We also revealed that the rate of NKX2.1, FOXE1,
      NKX2.5, and PAX8 mutations were low in patients with CH and athyreosis, in
      contrast to the higher rate of TSHR mutations.

PMID- 28455096
TI  - Androgenic mechanisms of sexual differentiation of the nervous system and
      behavior.
AB  - Testicular androgens are the major endocrine factor promoting masculine
      phenotypes in vertebrates, but androgen signaling is complex and operates via
      multiple signaling pathways and sites of action. Recently, selective androgen
      receptor mutants have been engineered to study androgenic mechanisms of sexual
      differentiation of the nervous system and behavior. The focus of these studies
      has been to evaluate androgenic mechanisms within the nervous system by
      manipulating androgen receptor conditionally in neural tissues. Here we review
      both the effects of neural loss of AR function as well as the effects of neural
      overexpression of AR in relation to global AR mutants. Although some studies have
      conformed to our expectations, others have proved challenging to assumptions
      underlying the dominant hypotheses. Notably, these studies have called into
      question both the primacy of direct, neural mechanisms and also the linearity of
      the relationship between androgenic dose and sexual differentiation of brain and
      behavior.

PMID- 28455097
TI  - Severity of Acute Kidney Injury in the Post-Lung Transplant Patient Is Associated
      With Higher Healthcare Resources and Cost.
AB  - OBJECTIVE: Perioperative risk factors and the clinical impact of acute kidney
      injury (AKI) and failure after lung transplantation are not well described. The
      incidences of AKI and acute renal failure (ARF), potential perioperative
      contributors to their development, and postdischarge healthcare needs were
      evaluated. DESIGN: Retrospective. SETTING: University hospital. PARTICIPANTS:
      Patients undergoing lung transplantation between January 1, 2011 and December 31,
      2015. MEASURED DATA: The incidences of AKI and ARF, as defined using the Risk,
      Injury, Failure, Loss, End-Stage Renal Disease criteria, were measured.
      Perioperative events were analyzed to identify risk factors for renal compromise.
      A comparison of ventilator days, intensive care unit (ICU) and hospital lengths
      of stay (LOS), 1-year readmissions, and emergency department visits was performed
      among AKI, ARF, and uninjured patients. MEASUREMENTS AND MAIN RESULTS: Ninety
      seven patients underwent lung transplantation; 22 patients developed AKI and 35
      patients developed ARF. Patients with ARF had significantly longer ICU LOS (12
      days v 4 days, p < 0.001); ventilator days (4.5 days v 1 day, p < 0.001); and
      hospital LOS (22.5 days v 14 days, p < 0.001) compared with uninjured patients.
      Patients with AKI also had significantly longer ICU and hospital LOS. Patients
      with ARF had significantly more emergency department visits and hospital
      readmissions (2 v 1 readmissions, p = 0.002) compared with uninjured patients. A
      univariable analysis suggested that prolonged surgical time, intraoperative
      vasopressor use, and cardiopulmonary bypass use were associated with the highest
      increased risk for AKI. Intraoperative vasopressor use and cardiopulmonary bypass
      mean arterial pressure <60 mmHg were identified as independent risk factors by
      multivariable analysis for AKI. CONCLUSION: The severity of AKI was associated
      with an increase in the use of healthcare resources after surgery and discharge.
      Certain risk factors appeared modifiable and may reduce the incidence of AKI and
      ARF.

PMID- 28455099
TI  - Membrane localization and dynamics of geranylgeranylated Rab5 hypervariable
      region.
AB  - The small GTPase Rab5 is a key regulator of endosomal trafficking processes and a
      marker for the early endosome. The C-terminal hypervariable region (HVR) of Rab5
      is post-translationally modified at residues Cys212 and Cys213 to accommodate two
      geranylgeranyl anchors (C20 carbon chain length) in order to associate Rab5 with
      the membrane. The structural role of the HVR regarding protein-early endosome
      membrane recruitment is not resolved due to its high degree of flexibility and
      lack of crystallographic information. Here, full-atomistic and coarse-grained
      molecular dynamics simulations of the truncated Rab5 HVR206-215 in three model
      membranes of increasing complexity (pure phospholipid bilayer, ternary membrane
      with cholesterol, six-component early endosome) were performed. Specific
      electrostatic interactions between the HVR206-215 Arg209 residue and the
      phosphate group of the inositol ring of PI(3)P were detected. This shows that
      PI(3)P acts as a first contact site of protein recruitment to the early endosome.
      The free energy change of HVR206-215 extraction from the bilayer was largest for
      the physiological negatively charged membrane. 5MUs coarse-grained simulations
      revealed an active recruitment of PI(3)P to the HVR206-215 supporting the
      formation of Rab5- and PI(3)P enriched signaling platforms.

PMID- 28455098
TI  - Computing osmotic permeabilities of aquaporins AQP4, AQP5, and GlpF from near
      equilibrium simulations.
AB  - Measuring or computing the single-channel permeability of
      aquaporins/aquaglyceroporins (AQPs) has long been a challenge. The measured
      values scatter over an order of magnitude but the corresponding Arrhenius
      activation energies converge in the current literature. Osmotic flux through an
      AQP was simulated as water current forced through the channel by kilobar
      hydraulic pressure or theoretically approximated as single-file diffusion. In
      this paper, we report large scale simulations of osmotic current under sub M
      gradient through three AQPs (water channels AQP4 and AQP5 and glycerol-water
      channel GlpF) using the mature particle mesh Ewald technique (PME) for which the
      established force fields have been optimized with known accuracy. These
      simulations were implemented with hybrid periodic boundary conditions devised to
      avoid the artifactitious mixing across the membrane in a regular PME simulation.
      The computed single-channel permeabilities at 5 degrees C and 25 degrees C are in
      agreement with recently refined experiments on GlpF. The Arrhenius activation
      energies extracted from our simulations for all the three AQPs agree with the in
      vitro measurements. The single-file diffusion approximations from our large-scale
      simulations are consistent with the current literature on smaller systems. From
      these unambiguous agreements among the in vitro and in silico studies, we observe
      the quantitative accuracy of the all-atom force fields of the current literature
      for water-channel biology. We also observe that AQP4, that is particularly rich
      in the central nervous system, is more efficient in water conduction and more
      temperature-sensitive than other water-only channels (excluding glycerol channels
      that also conduct water when not inhibited by glycerol).

PMID- 28455100
TI  - Acquisition and reversal of visual discrimination learning in APPSwDI/Nos2-/-
      (CVN) mice.
AB  - Studies of cognitive behavior in rodent models of Alzheimer's disease (AD) are
      the mainstay of academic and industrial efforts to find effective treatments for
      this disorder. However, in the majority of such studies, the nature of rodent
      behavioral tests is considerably different from the setting associated with
      cognitive assessments of individuals with AD. The recently developed touchscreen
      technique provides a more translational way of rodent cognitive testing because
      the stimulus (images in different locations on the screen) and reaction (touch)
      are similar to those employed in human test routines, such as the Cambridge
      Neuropsychological Test Automated Battery. Here, we used Visual Discrimination
      and Reversal of Visual Discrimination touchscreen tasks to assess cognitive
      performance of APPSwDI/Nos2-/- (CVN) mice, which express mutated human APP and
      have a homozygous deletion of the Nos2 gene. We revealed that CVN mice made more
      first-time errors and received more correction trials than WT mice across both
      discrimination and reversal phases, although mutation effect size was larger
      during the latter phase. These results indicate sensitivity of touchscreen-based
      measurements to AD-relevant mutations in CVN mice and warrant future touchscreen
      experiments aimed at evaluating other cognitive and motivational phenotypes in
      this AD mouse model.

PMID- 28455101
TI  - Sip-1 mutations cause disturbances in the activity of NMDA- and AMPA-, but not
      kainate receptors of neurons in the cerebral cortex.
AB  - Smad-interacting protein-1 (Sip1) [Zinc finger homeobox (Zfhx1b), Zeb2] is a
      transcription factor implicated in the genesis of Mowat-Wilson syndrome (MWS) in
      humans. MWS is a rare genetic autosomal dominant disease caused by a mutation in
      the Sip1 gene (aka Zeb2 or Zfhx1b) mapped to 2q22.3 locus. MWS affects 1 in every
      50-100 newborns worldwide. It is characterized by mental retardation, small
      stature, typical facial abnormalities as well as disturbances in the development
      of the cardio-vascular and renal systems as well as some other organs. Sip1
      mutations cause abnormal neurogenesis in the brain during development as well as
      susceptibility to epileptic seizures. In the current study we investigated the
      role of the Sip1 gene in the activity of NMDA-, AMPA- and KA- receptors. We
      showed that a particular Sip1 mutation in the mouse causes changes in the
      activity of both NMDA- and AMPA- receptors in the neocortical neurons in vitro.
      We demonstrate that neocortical neurons that have only one copy of Sip1
      (heterozygous, Sip1fI/wt), are more sensitive to both NMDA- and AMPA- receptors
      agonists as compared to wild type neurons (Sip1wt/wt). This is reflected in
      higher amplitudes of agonist induced Ca2+ signals as well as a lower half maximal
      effective concentration (EC50). In contrast, neurons from homozygous Sip1 mice
      (Sip1fI/fI), demonstrate higher resistance to these respective receptor agonists.
      This is reflected in lower amplitudes of Ca2+-responses and so a higher
      concentration of receptor activators is required for activation.

PMID- 28455102
TI  - Sleep deprivation accelerates the progression of alzheimer's disease by
      influencing Abeta-related metabolism.
AB  - Sleep disorders have previously been connected with the neurodegenerative
      pathology of Alzheimer's disease (AD) due to the aggregation of beta
      amyloid(Abeta)peptides and tau proteinsinduced by sleep deprivation (SD).
      However, the underlying mechanisms remain unclear. Therefore, this study was
      performed to clarify how Abeta-related metabolism is regulated after SD. Three
      month-old Sprague-Dawley rats (250-300g) were randomly divided into 5 groups: two
      SD groups(i.e.,SD-2d and SD-4d), two platform control groups(i.e.,PC-2d and PC
      4d) and a home cage control group (CC). For the two SD groups, themodified
      multiple platform method (MMPM) was used to induce SD.Our experiments confirmed
      that SD impaired cognitive function and increased the levels of Abeta peptides, a
      hallmark of AD. Additionally, we found that SD significantly increasedthe levels
      of the beta-site amyloid precursor protein (APP)-cleaving enzyme 1(BACE1, beta
      secretase), but had little impacton the levels of Abeta-degradationenzymes.This
      resultmay be the main cause of the over-expression of Abeta1-42 and Abeta1-40.
      Our results suggested that SD accelerates the progression of AD bymodulating
      Abeta-related metabolism. This findinghasimportant implications for the diagnosis
      and prevention of AD.

PMID- 28455103
TI  - Transcranial Doppler ultrasonography in the assessment of neurovascular coupling
      responses to cognitive examination in healthy controls: A feasibility study.
AB  - BACKGROUND: We tested the hypothesis that paradigms from the Addenbrooke's
      Cognitive Examination (ACE-III), including those that had not been studied using
      TCD previously (novel) versus those which had been (established), would elicit
      changes in CBF velocity (CBFv). NEW METHOD: Healthy subjects were studied with
      bilateral transcranial Doppler (TCD), beat-to-beat blood pressure (Finapres),
      continuous electrocardiogram (ECG), and end-tidal CO2 (nasal capnography). After
      a 5-min baseline recording, cognitive tests of the ACE-III were presented to
      subjects, covering attention (SUB7, subtracting 7 from 100 sequentially),
      language (REP, repeating words and phrases), fluency (N-P, naming words),
      visuospatial (DRAW, clock-drawing), and memory (MEM, recalling name and address).
      An event marker noted question timing. RESULTS: Forty bilateral data sets were
      obtained (13 males, 37 right-hand dominant) with a median age of 31 years (IQR 22
      52). Population normalized mean peak CBFv% in the dominant and non-dominant
      hemispheres, respectively, were: SUB7 (11.3+/-9.6%, 11.2+/-10.5%), N-P (12.7+/
      11.7%, 11.5+/-12.0%), REP (12.9+/-11.7%, 11.6+/-11.6%), DRAW (13.3+/-11.7%,
      13.2+/-15.4%) and MEM (13.2+/-10.3%, 12.0+/-10.1%). There was a significant
      difference between the dominant and non-dominant CBFv responses (p<0.008), but no
      difference between the amplitude of responses. COMPARISON WITH EXISTING METHODS:
      For established paradigms, our results are in excellent agreement to what has
      been found previously in the middle cerebral artery. CONCLUSIONS: Cognitive
      paradigms derived from the ACE-III led to significant lateralised changes in CBFv
      that were not distinct for novel paradigms. Further work is needed to assess the
      potential of paradigms to improve the interpretation of cognitive assessments in
      patients at risk of mild cognitive impairment.

PMID- 28455104
TI  - A comparison of tuberculosis diagnostic systems in a retrospective cohort of HIV
      infected children in Rio de Janeiro, Brazil.
AB  - OBJECTIVES: The diagnosis of pediatric tuberculosis (TB) presents many
      challenges, and is further complicated in HIV-infected patients. While many
      diagnostic systems have been proposed, there is no pediatric TB diagnosis gold
      standard. The outcomes of four TB diagnostic systems in HIV-infected children
      were compared in this study. METHODS: A retrospective cohort study was conducted
      at a TB/HIV reference hospital in Rio de Janeiro. HIV-infected pediatric patients
      evaluated for TB from 1998 to 2010 were reassessed using four diagnostic systems:
      Kenneth Jones, 1969; Tidjani, 1986; Ben Marais, 2006; Brazilian Ministry of
      Health, 2010. Results were compared to standardized diagnoses made by an expert
      panel of physicians. RESULTS: Of the 121 patients in the study cohort, the expert
      panel diagnosed 64 as TB and 57 as not TB cases. The Tidjani system showed the
      highest diagnostic accuracy, with and without the inclusion of microbiological
      data. The Tidjani and Kenneth Jones systems produced fewer false-positives, and
      the Ben Marais and Ministry of Health fewer false-negatives. Across systems,
      there was little agreement between TB diagnoses. CONCLUSIONS: In HIV-infected
      pediatric patients, the Ben Marais and Ministry of Health systems are useful for
      TB diagnostic screening, whereas the Tidjani and Kenneth Jones systems are best
      used in a reference center setting.

PMID- 28455105
TI  - Trace element intakes should be revisited in burn nutrition protocols: A cohort
      study.
AB  - BACKGROUND & AIMS: Due to inflammatory and hypermetabolic responses and to
      extensive exudative trace element (TEs) losses, major burn patients have
      substantially increased nutritional requirements. To date, information is only
      available for Cu, Se, and Zn. We aimed at analyzing losses of 12 TEs and Mg
      through burn wound exudation and corresponding plasma concentrations during the
      first week after burn injury, and to evaluate the impact of current TE repletion
      protocols. METHODS: Burn wound exudate was collected under negative pressure in
      15 adult patients burned 29 +/- 20% of body surface (TBSA) for 8 days after
      injury. Two samples were collected daily. The TE concentrations were measured by
      inductively coupled plasma mass spectrometry (ICP-MS). Losses and serum
      concentrations were compared to intakes. RESULTS: For the majority of 12 TEs, the
      highest losses were observed on day 1, and declined thereafter. Despite Cu
      supplementation (4.23 mg/day) serum levels remained below reference values. Se
      supplements (745 MUg/day) normalized and even increased serum levels to upper
      normal value. Despite large supplements (Zn 67.5 mg/day), serum Zn values
      remained below reference range. Large exudative losses of B, Br and Mg were
      found, as well as of Fe and I, with the latter being probably due to
      contamination. CONCLUSION: Current nutritional Cu, Se, Zn repletion protocols in
      major burn patients which were based on measured exudative losses should be
      revised to include higher Cu and lower Se doses, as well as planned Mg
      administration. In burns <20% TBSA and for the other TEs the recommended
      parenteral nutrition TE doses appear sufficient.

PMID- 28455106
TI  - Late dinner impairs glucose tolerance in MTNR1B risk allele carriers: A
      randomized, cross-over study.
AB  - BACKGROUND & AIMS: Late-night dinner eating is associated with increased risk for
      type-2 diabetes. The underlying mechanism is unclear. One explanatory hypothesis
      is that the concurrence of elevated circulating melatonin and high glucose
      concentrations (characterizing late eating) leads to impaired glucose tolerance.
      However, to date no study has tested the influence of physiological melatonin
      concentrations on glucose-tolerance. The discovery of melatonin receptor MTNR1B
      as a diabetes risk gene provides evidence for a role of physiological levels of
      melatonin in glucose control. The aim of our study was to test the hypothesis
      that elevated endogenous melatonin concentrations worsen glucose control when
      eating late. Registered under ClinicalTrials.gov Identifier no. NCT03003936.
      METHODS: We performed a randomized, cross-over trial to compare glucose tolerance
      in the presence (late dinner) or absence (early dinner) of elevated physiological
      melatonin concentrations and we compared the results between homozygous carriers
      and non-carriers of the MTNR1B risk allele. RESULTS: The concurrence of meal
      timing with elevated endogenous melatonin concentrations resulted in impaired
      glucose tolerance. This effect was stronger in MTNR1B risk-carriers than in non
      carriers. Furthermore, eating late significantly impaired glucose tolerance only
      in risk-carriers and not in the non-risk carriers. CONCLUSIONS: The interaction
      of dinner timing with MTNR1B supports a causal role of endogenous melatonin in
      the impairment of glucose tolerance. These results suggest that moving the dinner
      to an earlier time may result in better glucose tolerance specially in MTNR1B
      carriers. CLINICAL TRIAL REGISTRATION:
      https://clinicaltrials.gov/ct2/show/NCT03003936.

PMID- 28455107
TI  - Sleep quality and duration in relation to memory in the elderly: Initial results
      from the Hellenic Longitudinal Investigation of Aging and Diet.
AB  - BACKGROUND: Sleep is crucial for cognition, particularly for memory, given its
      complex association with neurodegenerative processes. The aim of the present
      study was to examine the association between sleep quality as well as sleep
      duration and memory performance in a Greek elderly population. SETTING: Cross
      sectional design in the Hellenic Longitudinal Investigation of Aging and Diet
      (HELIAD), a population representative study of Greek elderly (65years or older).
      METHODS: Data from 1589 participants free of sleep medication were included.
      Sleep quality was estimated by using the Sleep Scale from the Medical Outcomes
      Study. An extensive neuropsychological assessment examining memory was
      administered to each participant. Linear regression analyses were used to examine
      whether sleep quality (higher score, poor quality) and/or sleep duration were
      associated with memory expressed in the form of a z-score. Age, sex, education,
      and body mass index were included as covariates. The main analyses were conducted
      first on the total sample, then with the exclusion of demented participants, and
      finally with the exclusion of both demented and participants with Mild Cognitive
      Impairment (MCI). We then conducted further analyses on the non-demented, non-MCI
      group, initially stratified by Apolipoprotein E-epsilon4 gene. We further
      examined the role of co-morbidities, as well as the association between sleep
      duration groups and memory. We also explored any interaction effect between sex
      and sleep quality/duration on memory. We then examined the associations between
      components of sleep measures and memory scores. Lastly, we examined the
      associations between sleep quality/duration and verbal/non-verbal memory
      separately. RESULTS: In the total sample, we noted significant associations
      between sleep duration and memory (B=-0.001, p<=0.0001), but not for sleep
      quality and memory (B=-0.038, p=0.121). After excluding the demented
      participants, the associations were significant for: sleep quality and memory (B=
      0.054, p=0.023), and sleep duration and memory (B=-0.001, p<=0.0001). After
      excluding both the MCI and the demented subjects, the associations between sleep
      quality and memory (B=-0.065, p=0.006), and sleep duration and memory (B=-0.001,
      p=0.003) were still significant. The association between the sleep duration
      groups and memory function was also significant, such that poor memory
      performance was associated with the longer sleep duration group. The results
      remained significant even after controlling for the co-morbidities, as well as
      after adding in the model anxiety and depression as covariates. Associations
      between sleep quality and memory, and sleep duration and memory were present in
      the ApoE-epsilon4 non-carriers. The individual sleep questions that were probably
      shown to be driving the associations between sleep and memory were: time to fall
      asleep, sleep not quiet, getting enough sleep to feel rested upon waking in the
      morning, and getting the amount of sleep needed. Sleep duration was associated
      with both verbal and non-verbal memory, while sleep quality was only associated
      with verbal memory. CONCLUSION: Poor sleep quality and longer sleep duration were
      linked to low memory performance, independent of demographic and clinical
      factors, in a large sample of cognitively healthy older Greek adults. Other
      parameters than sleep and memory measurements could play an important role on the
      association. Levels of melatonin, or circadian rhythms dysregulation might play a
      crucial role in the above associations.

PMID- 28455108
TI  - Implementing consultation audio-recordings and question prompt lists into routine
      cancer care: How can we address healthcare providers' barriers?

PMID- 28455110
TI  - [Combination of hemodialysis and hemofiltration in severe caffeine intoxication].
AB  - A 21-year-old man ingested 75g of pure caffeine, in an attempt to commit suicide.
      This represents 7.5 times the minimal lethal dose. Caffeine, 1,3,7
      trimethylxanthine, is the most widely consumed psychoactive compound worldwide.
      It is mostly found in coffee, tea, energizing drinks and in some drugs. However,
      it has become really easy to obtain pure caffeine (powder or tablets) on the
      Internet. Mechanisms of action are dose-dependent. When caffeine overdosing
      occurs, neurologic, cardiovascular and renal systems are mainly affected. Severe
      intoxication can be fatal. No antidote is available and treatment is purely
      symptomatic. Hemoperfusion has previously been carried out in the 1990's to treat
      patients with caffeine intoxication. Since 2009, hemodialysis and hemofiltration
      have proposed as well. Our patient was successfully treated with a combination of
      hemodiafiltration, intermittent and then continuous.

PMID- 28455109
TI  - Bronchoprotective mechanisms for specialized pro-resolving mediators in the
      resolution of lung inflammation.
AB  - Bronchi are exposed daily to irritants, microbes and allergens as well as
      extremes of temperature and acid. The airway mucosal epithelium plays a pivotal
      role as a sentinel, releasing alarmins when danger is encountered. To maintain
      homeostasis, an elaborate counter-regulatory network of signals and cellular
      effector mechanisms are needed. Specialized pro-resolving mediators (SPMs) are
      chemical mediators that enact resolution programs in response to injury,
      infection or allergy. SPMs are enzymatically derived from essential
      polyunsaturated fatty acids with potent cell-type specific immunoresolvent
      properties. SPMs signal by engaging cell-based receptors to turn off acute
      inflammatory responses and restore tissue homeostasis. Several common lung
      diseases involving the airways, including asthma, chronic obstructive pulmonary
      disease (COPD), and cystic fibrosis (CF), are characterized by unresolved
      bronchial inflammation. In preclinical murine models of lung disease, SPMs carry
      potent bronchoprotective actions. Here, we review cellular and molecular effects
      for SPM-initiated catabasis in the lung and their human translation.

PMID- 28455111
TI  - The incongruity of workplace bullying victimization and inclusive excellence.
AB  - PURPOSE: Bullying occurs frequently-and with significant negative outcomes-in
      workplace settings. Once established, bullying endures in the workplace,
      requiring the interaction of a bully perpetrator and an intended target who takes
      on the role of victim. Not every target becomes a victim, however. The purpose of
      this study is to investigate the processes by which targets, intended objects of
      bullies' affronts, become victims, those individuals who experience ongoing
      emotional injury in response to bullies' affronts, and to clarify how bullying
      victimization impedes inclusive excellence in the workplace. DESIGN: The design
      for this study was pragmatic utility, an inductive research approach grounded in
      assumptions of hermeneutics. METHODS: The pragmatic utility process involved the
      investigators' synthesis of descriptions from a broad, interdisciplinary
      published literature. Integrating knowledge from their previous research and
      practice experiences with the pragmatic utility process, they derived qualitative
      features of victims' experiences, differentiating target from victim in bullying
      encounters. FINDINGS: For those targets who ultimately are victimized, response
      to bullies' affronts extends far beyond the immediate present. Redolence of
      personal, lived experience revives bygone vulnerabilities, and naive
      communication and relationship expectations reinforce a long-standing,
      impoverished sense. That sense couples with workplace dynamics to augment a
      context of exclusion. CONCLUSION: Findings suggest that, as Heidegger contended,
      we are our histories. Personal history demonstrates a significance influence on
      the manifestation of bullying victimization, acting to distance them from their
      workplace peers and to impede inclusive excellence.

PMID- 28455113
TI  - A synopsis of brown adipose tissue imaging modalities for clinical research.
AB  - Body weight gain results from a chronic excess of energy intake over energy
      expenditure. Accentuating endogenous energy expenditure has been accorded
      considerable attention ever since the presence of brown adipose tissue (BAT) in
      adult humans was recognized, given that BAT is known to increase energy
      expenditure via thermogenesis. Besides classic BAT, significant strides in our
      understanding of inducible brown adipocytes have been made regarding its
      development and function. While it is ideal to study BAT histologically, its
      relatively inaccessible anatomical locations and the inherent risks associated
      with biopsy preclude invasive techniques to evaluate BAT on a routine basis.
      Thus, there has been a surge in interest to employ non-invasive methods to
      examine BAT. The gold standard of non-invasive detection of BAT activation is 18F
      fluorodeoxyglucose positron emission tomography (PET) with computed tomography
      (CT). However, a major limitation of PET/CT as a tool for human BAT studies is
      the clinically significant doses of ionizing radiation. More recently, several
      other imaging methods, including single-photon emission computed tomography
      (SPECT), magnetic resonance imaging (MRI), infrared thermography (IRT)/thermal
      imaging and contrast ultrasonography (US) have been developed in hopes that they
      would allow non-invasive, quantitative measures of BAT mass and activity with
      lower costs. This review focuses on such methods to detect human BAT activation
      and white adipose tissue (WAT) browning to prompt the establishment of BAT
      centric strategies for augmenting energy expenditure and combatting obesity.
      Clinical validation of these methods will most likely expand the scope and
      flexibility of future BAT studies.

PMID- 28455112
TI  - Building a mentoring network.
AB  - BACKGROUND: Mentoring has long been regarded as one of the key components of
      research training and faculty development. PURPOSE: The Robert Wood Johnson
      Foundation Nurse Faculty Scholars program purposely facilitated scholars'
      development of a mentoring network by providing each individual with three
      mentors: a school-of-nursing mentor (primary), a university-based non-nurse
      research mentor (research), and a nationally-recognized nurse leader at another
      university (national). METHOD: The Mentorship Effectiveness Scale was used to
      assess the effectiveness of each type of mentor in the first five completed
      cohorts. DISCUSSION: The ratings of mentorship effectiveness for all three kinds
      of mentors were generally high. Scholars valued most their mentors' support and
      advocacy; the biggest weakness in dealing with all mentors was accessibility.
      CONCLUSION: Even when one mentor proved a poor match, another mentor turned out
      to be an advocate and helpful, thus reaffirming the benefits of a mentoring
      network as opposed to only a single mentoring relationship. One lesson learned is
      the importance of preparing mentors for their role via written materials, in
      person or phone orientations, and discussions at the annual meeting.

PMID- 28455114
TI  - Association of fasting serum insulin and cancer mortality in a healthy population
      - 28-year follow-up of the French TELECOM Study.
AB  - AIMS: Epidemiologic, pharmacoepidemiologic and pathophysiologic evidence points
      consistently to an association between type 2 diabetes and cancer. This
      association could be explained by hyperinsulinemia induced by insulin resistance.
      We studied the association between fasting serum insulin (FSI) and cancer
      mortality in a population of non-diabetic individuals. METHODS: We followed 3117
      healthy workers (50.2% women), included in the TELECOM cohort study, between 1985
      and 1987; their median age was 38 years (Q1-Q3=30-50). Baseline FSI was measured
      by radioimmunoassay, the INSI-PR method. People with diabetes or cancer at
      baseline were excluded. Vital status and causes of death were available until
      December 2013. The association between FSI and cancer deaths was analysed by sex,
      using a Cox proportional hazards model with age as the time scale, adjusting for
      body mass index, smoking habits, alcohol consumption, occupational category and
      ethnic origin. RESULTS: After a 28-year follow-up, 330 (10.6%) deaths were
      reported, among which, 150 were cancer-related (80 men, 70 women). In men, the
      association between FSI and death by cancer was J-shaped: compared to the average
      FSI of 7.1mU/L, men with 5mU/L and 12.9mU/L had respectively adjusted hazard
      ratios (HR) of 1.88 (95% confidence interval, 1.00-3.56) and 2.30 (95% CI, 1.34
      3.94). Among women, no significant association was found (adjusted HR, 1.03; 95%
      CI, 0.96-1.11) for an increase of 1mU/L in FSI. CONCLUSION: These results
      strengthen the hypothesis of an independent risk of cancer death associated with
      extreme values of FSI, mainly the highest, among men, but not among women.

PMID- 28455115
TI  - Reduced Free Communication of the Subarachnoid Space Within the Optic Canal in
      the Human.
AB  - PURPOSE: Recent studies in patients demonstrated that cerebrospinal fluid does
      not flow continuously between the intracranial subarachnoid space (SAS) and the
      space around the optic nerve in the orbit. Its anatomic basis remains elusive.
      The objective of this study was to use a novel anatomic technology, the epoxy
      sheet plastination, to reveal the configuration of the fibrous structures within
      the optic canal and their relationship with the optic nerve, SAS, and ophthalmic
      artery. DESIGN: A human cadaveric study. METHODS: Nine cadaveric heads (subject
      age 54-87 years) without optic neuropathy were prepared as sets of transverse,
      coronal, and sagittal plastinated sections. Three of them were pretreated with
      hematoxylin staining via the SAS irrigation before sectioning and plastination.
      The prepared sections were examined under a stereoscope and a confocal
      microscope. RESULTS: The results showed that (1) the pia and arachnoid maters
      merged within the optic canal, (2) a dense trabecular mesh network was
      distributed in the orbital part of the canal, and (3) some optic nerve sheath
      (ONS) fibers intermingled with the tendinous fibers of the extraocular muscles
      and attached to the periosteum of the sphenoid bone, rather than entirely
      continuing with the inner layer of the dura mater. CONCLUSIONS: This study
      identified and traced the fibrous components within the optic canal and revealed
      their nature, architecture, and relationship with surroundings and concluded that
      in the human, free communication of the SAS between the intracranial cavity and
      ONS was significantly reduced.

PMID- 28455116
TI  - Self-reported Receipt of Dilated Fundus Examinations Among Patients With
      Diabetes: Medicare Expenditure Panel Survey, 2002-2013.
AB  - PURPOSE: To evaluate self-reported adherence to diabetic retinopathy screening
      examinations among diabetic subjects. DESIGN: Retrospective, population-based
      cross-sectional study. METHODS: Medical Expenditure Panel Survey (MEPS)
      consolidated full-year and prescribed drugs data from 2002-2013 were reviewed;
      multivariable logistic regression was used to identify patient characteristics as
      potential barriers to receiving examinations. RESULTS: Of 13 299 persons in the
      MEPS sample, only 39.62% (95% confidence interval [CI] 38.56%-40.67%) reported
      receiving annual dilated eye examinations, and 90.31% (CI 89.70%-90.91%) reported
      ever having received an eye examination. Significant factors related to ever
      receiving an eye examination included completed high school (odds ratio [OR] =
      1.53; CI, 1.33-1.75), bachelor's degree or higher (OR = 1.94; CI, 1.56-2.41),
      private health insurance (OR = 2.07; CI, 1.70-2.52), public insurance (OR = 1.90;
      CI, 1.56-2.31), household income >400% of the poverty threshold (OR = 1.75; CI,
      1.36-2.25), prescribed diabetes medication (OR = 1.45; CI, 1.27-1.65), diabetic
      kidney disease (OR = 1.31; CI, 1.08-1.59), prior foot examination (OR = 1.49; CI,
      1.28-1.74), prior hemoglobin A1c test (OR = 1.45; CI, 1.28-1.64), and having a
      usual care provider (OR = 1.50; CI, 1.25-1.80). Self-reported Asian ethnicity (OR
      = 0.51; CI, 0.39-0.65), needing assistance for at least 3 months (OR = 0.79; CI,
      0.62-1.00), and proxy needed to fill out the survey (OR = 0.72; CI, 0.61-0.85)
      were associated with lower odds of reporting ever having received a dilated eye
      examination. CONCLUSIONS: In this national-representative sample, 90.31% of
      patients with diabetes reported ever having a dilated eye examination; only
      39.62% reported receiving one annually as recommended. These low rates appear
      associated with possibly modifiable factors, including having a regular care
      provider, increasing access to care, enrollment in health insurance, and higher
      education.

PMID- 28455117
TI  - European Paediatric Association, the Union of National European Paediatric
      Societies and Associations Turns 40 Years: What This European Platform Offers to
      Pediatricians.

PMID- 28455118
TI  - Author's reply: sliding versus conventional functional end-to-end anastomosis for
      colon cancer surgery: a randomized controlled trial.

PMID- 28455121
TI  - Comprehensive two-dimensional gas chromatography: A perspective on processes of
      modulation.
AB  - The first comprehensive two-dimensional gas chromatography (GC*GC) experiment was
      reported about 25 years ago [J. Chromatogr. Sci. 29 (1991) 227-231]; the GC*GC
      process was made possible by the development of a transfer device, defined as
      modulator. The process of modulation enables the isolation of effluent segments
      from the first column, and their re-injection onto the second column, in a
      continuous and sequential manner throughout the analysis. Over the years, many
      types of modulation systems have been introduced, each with specific advantages
      and disadvantages. Cryogenic systems are, at present, the most popular devices
      and represent the most effective form of modulation. The present contribution is
      focused on possible future scenarios, with respect to modulation, and as a
      consequence related to comprehensive GC, in general. The development of new forms
      of modulation may open the road to a more widespread use of GC*GC technologies.

PMID- 28455119
TI  - Changes of cecal microflora in chickens following Eimeria tenella challenge and
      regulating effect of coated sodium butyrate.
AB  - Eimeria tenella, one of the most important parasitic protozoa in the genus
      Eimeria, is responsible for chicken caecal coccidiosis resulting in huge economic
      losses to poultry industry. The present study investigated the changes in caecal
      microflora of E. tenella-infected chickens and the regulating effect of coated
      sodium butyrate, a potential alternative to antibiotics. Using high-throughput
      sequencing of 16S rRNA V3-V4 region of bacteria we found significant changes in
      caecal microflora of E. tenella-infected chickens indicated by an increase of
      Firmicutes (mainly Ruminococcaceae, Lachnospiraceae and vadin BB60) and
      Proteobacteria (mainly Enterobacteriaceae) and a decrease of Bacteroidetes
      (predominantly Bacteroidaceae). Inclusion of coated sodium butyrate in the diet
      of chickens per se had no significant effect on caecal microflora of normal
      healthy chickens but significantly prevented the increase in Firmicute abundance
      and decrease of Bacteroidetes abundance in E. tenella-infected birds. No
      significant changes to caecal microflora were observed at the phylum level
      between control and E. tenella-infected birds given coated sodium butyrate. In
      conclusion, our results show that coated sodium butyrate can balance the
      disorders of cecal microflora caused by E. tenella; thus, it can be a useful
      supplement for the control of avian coccidiosis.

PMID- 28455120
TI  - Obstructive sleep apnea is associated with increased QT corrected interval
      dispersion: the effects of continuous positive airway pressure.
AB  - INTRODUCTION: Severe obstructive sleep apnea is associated with increased QT
      corrected interval dispersion and continuous positive airway pressure is thought
      to improve this arrhythmogenic marker. OBJECTIVE: The aim of the study was to
      determine the decrease of ratio of cardiovascular risk in patients with
      obstructive sleep apnea. METHODS: The study included 65 patients with severe
      obstructive sleep apnea who had an apnea-hypopnea index score of >30. Each
      patient underwent 12-channel electrocardiogram monitoring and polysomnography.
      Patients with an apnea-hypopnea index score of <5 were used as the control group.
      The control group also underwent electrocardiogram monitoring and polysomnography
      testing. The QT corrected interval dispersion levels of both groups were
      calculated. Three months after continuous positive airway pressure treatment,
      electrocardiogram recordings were obtained from the 65 patients with severe
      obstructive sleep apnea again, and their QT corrected interval dispersion values
      were calculated. RESULTS: There were 44 male and 21 female patients with severe
      obstructive sleep apnea syndrome. The age, gender, body mass index, initial
      saturation, minimum saturation, average saturation, and desaturation index were
      determined in both groups. The QT corrected intervals of the obstructive sleep
      apnea patients (62.48+/-16.29ms) were significantly higher (p=0.001) than those
      of the control group (29.72+/-6.30ms). There were statistically significant
      differences between the QT corrected values before and after the continuous
      positive airway pressure treatment, with pretreatment QT corrected intervals of
      62.48+/-16.29ms and 3-month post-treatment values of 41.42+/-16.96ms (p=0.001).
      There was a positive and significant correlation between QT corrected interval
      dispersion periods and the apnea-hypopnea index and hypopnea index in obstructive
      sleep apnea patients (p=0.001; r=0.71; p=0.001; r=0.679, respectively).
      CONCLUSION: Continuous positive airway pressure treatment reduced the QT
      corrected interval dispersion in patients with severe obstructive sleep apnea. In
      addition, shortening the QT corrected interval dispersion periods in patients
      with severe obstructive sleep apnea may reduce their risk of arrhythmias and
      cardiovascular disease.

PMID- 28455122
TI  - Kids'Cam: An Objective Methodology to Study the World in Which Children Live.
AB  - INTRODUCTION: This paper reports on a new methodology to objectively study the
      world in which children live. The primary research study (Kids'Cam Food
      Marketing) illustrates the method; numerous ancillary studies include exploration
      of children's exposure to alcohol, smoking, "blue" space and gambling, and their
      use of "green" space, transport, and sun protection. METHODS: One hundred sixty
      eight randomly selected children (aged 11-13 years) recruited from 16 randomly
      selected schools in Wellington, New Zealand used wearable cameras and GPS units
      for 4 days, recording imagery every 7 seconds and longitude/latitude locations
      every 5 seconds. Data were collected from July 2014 to June 2015. Analysis
      commenced in 2015 and is ongoing. Bespoke software was used to manually code
      images for variables of interest including setting, marketing media, and product
      category to produce variables for statistical analysis. GPS data were extracted
      and cleaned in ArcGIS, version 10.3 for exposure spatial analysis. RESULTS:
      Approximately 1.4 million images and 2.2 million GPS coordinates were generated
      (most were usable) from many settings including the difficult to measure aspects
      of exposures in the home, at school, and during leisure time. The method is
      ethical, legal, and acceptable to children and the wider community. CONCLUSIONS:
      This methodology enabled objective analysis of the world in which children live.
      The main arm examined the frequency and nature of children's exposure to food and
      beverage marketing and provided data on difficult to measure settings. The
      methodology will likely generate robust evidence facilitating more effective
      policymaking to address numerous public health concerns.

PMID- 28455124
TI  - [Isolated conjunctival lymphangioma: A case report].

PMID- 28455123
TI  - Neighborhood Environment and Cognition in Older Adults: A Systematic Review.
AB  - CONTEXT: Some evidence suggests that treating vascular risk factors and
      performing mentally stimulating activities may delay cognitive impairment onset
      in older adults. Exposure to a complex neighborhood environment may be one
      mechanism to help delay cognitive decline. EVIDENCE ACQUISITION: PubMed, Web of
      Science, and ProQuest Dissertation and Theses Global database were systematically
      reviewed, identifying 25 studies published from February 1, 1989 to March 5, 2016
      (data synthesized, May 3, 2015 to October 7, 2016). The review was restricted to
      quantitative studies focused on: (1) neighborhood social and built environment
      and cognition; and (2) community-dwelling adults aged >=45 years. EVIDENCE
      SYNTHESIS: The majority of studies were cross-sectional, U.S.-based, and found at
      least one significant association. The diversity of measures and neighborhood
      definitions limited the synthesis of findings in many instances. Evidence was
      moderately strong for an association between neighborhood SES and cognition, and
      modest for associations between neighborhood demographics, design, and
      destination accessibility and cognition. Most studies examining effect
      modification found significant associations, with some evidence for effect
      modification of the neighborhood SES-cognition association by individual-level
      SES. No studies had low risk of bias and many tested multiple associations that
      increased the chance of a statistically significant finding. Considering the
      studies to date, the evidence for an association between neighborhood
      characteristics and cognition is modest. CONCLUSIONS: Future studies should
      include longitudinal measures of neighborhood characteristics and cognition;
      examine potential effect modifiers, such as sex and disability; and study
      mediators that may help elucidate the biological mechanisms linking neighborhood
      environment and cognition.

PMID- 28455125
TI  - Relapse to cocaine seeking in an invertebrate.
AB  - Addiction is characterised by cycles of compulsive drug taking, periods of
      abstinence and episodes of relapse. The extinction/reinstatement paradigm has
      been extensively used in rodents to model human relapse and explore underlying
      mechanisms and therapeutics. However, relapse to drug seeking behaviour has not
      been previously demonstrated in invertebrates. Here, we used a cocaine
      conditioned place preference (CPP) paradigm in the flatworm, planarian, followed
      by extinction and reinstatement of drug seeking. Once baseline preference was
      established for one of two distinctly textured environments (i.e. compartments
      with a coarse or smooth surface), planarian received pairings of cocaine (5MUM)
      in the non-preferred, and vehicle in the most preferred, environment, and were
      tested for conditioning thereafter. Cocaine produced robust CPP, measured as a
      significant increase in the time spent in the cocaine-paired compartment.
      Subsequently, planarian underwent extinction training, reverting back to their
      original preference within three sessions. Brief exposure to cocaine (5MUM) or
      methamphetamine (5MUM) reinstated cocaine-seeking behaviour. By contrast, the
      high affinity dopamine transporter inhibitor, (N-(n-butyl)-3alpha-[bis (4
      fluorophenyl) methoxy]-tropane) (JHW007), which in rodents exhibits a
      neurochemical and behavioural profile distinct from cocaine, was ineffective. The
      present findings demonstrate for the first time reinstatement of extinguished
      cocaine seeking in an invertebrate model and suggest that the long-term
      adaptations underlying drug conditioning and relapse are highly conserved through
      evolution.

PMID- 28455126
TI  - Neurochemical arguments for the use of dopamine D4 receptor stimulation to
      improve cognitive impairment associated with schizophrenia.
AB  - BACKGROUND: Dopamine (DA) D4 receptors have been implicated in schizophrenia and
      the ability of some atypical antipsychotic drugs (APDs) to improve the cognitive
      impairment associated with schizophrenia (CIAS). Systemic administration of a D4
      agonist, PD168077, at a sub-effective dose, together with a sub-effective dose of
      lurasidone, an atypical APD which is a weak D4 receptor antagonist, reversed the
      deficit in novel object recognition (NOR) in rats treated subchronically with
      phencyclidine (PCP), a rodent model of CIAS. Atypical APDs potentially stimulate
      D4Rs via their ability to enhance DA release in key brain areas related to
      cognition. However, some atypical APDs are relatively potent D4 antagonists at
      clinical dosages, including clozapine, and risperidone. The D4 antagonist,
      L745870, blocked the ability of clozapine, but not lurasidone, to reverse the NOR
      deficit in rats. METHODS: The purpose of this study was to determine the effects
      of a selective D4 agonist and antagonist, alone, and as pretreatment with
      lurasidone, on neurotransmitter efflux in mouse medial prefrontal cortex (mPFC)
      and dorsal striatum (dSTR), using in vivo microdialysis. RESULTS AND DISCUSSION:
      PD168077 alone, and in combination with sub-effective dose lurasidone, increased
      DA and acetylcholine (ACh) efflux in mPFC, but only DA efflux in dSTR. L745870
      had no effect on neurotransmitter efflux on its own or on the ability of
      lurasidone to increase cortical or striatal neurotransmitter efflux. These
      results indicate D4 receptor agonism alone is sufficient to increase cortical DA
      and ACh efflux without interfering with the effects of lurasidone and possibly
      other atypical APDs on extracellular cortical DA and ACh levels. A D4 agonist may
      be useful for treating CIAS, especially as augmentation of those atypical APDs
      which are not potent D4 antagonists.

PMID- 28455127
TI  - Oxidative stress in Mayaro virus infection.
AB  - Mayaro virus (MAYV) is a neglected tropical arbovirus that causes a febrile
      syndrome that is sometimes accompanied by incapacitating arthritis/arthralgia.
      The pathogenesis of MAYV has not been completely defined and oxidative stress
      mediated by an increase in reactive oxygen species (ROS) and/or depletion of
      antioxidant defences has been found to contribute to several aspects of viral
      disease. To investigate whether MAYV induced oxidative stress in host cells, we
      monitored ROS production, oxidative stress markers and antioxidant defences at
      different time points after infection. Our results show that MAYV induced
      significant oxidative stress in infected HepG2 cells, as indicated by the
      increase of malondialdehyde (MDA) and protein carbonyl levels, and by a
      significant decrease of the reduced versus oxidized glutathione (GSH/GSSG) ratio.
      Generally, MAYV-infected HepG2 cells also showed an increase in antioxidant
      defences. We observed an increase in the superoxide dismutase (SOD) and catalase
      (CAT) activities and the total glutathione content. To determine whether similar
      effects occurred in other cell types, we evaluated the ROS, MDA and SOD activity
      levels in J774 cells after MAYV infection. Similar to our observations in HepG2
      cells, the J774 cells showed an increase in ROS, MDA and total SOD activity
      following MAYV infection. Thus, since the cellular redox environment is
      influenced by the production and removal of ROS, we hypothesize that the
      overproduction of ROS was responsible for the oxidative stress in response to the
      MAYV infection despite the increase in the antioxidant status. This study is the
      first report on the involvement of oxidative stress during MAYV infection.
      Collectively, our data shed light on some mechanisms that are operational in host
      cells following exposure to MAYV.

PMID- 28455129
TI  - Pediatrician-Parent Conversations About Human Papillomavirus Vaccination: An
      Analysis of Audio Recordings.
AB  - PURPOSE: We sought to establish which human papillomavirus (HPV) vaccine
      communication approaches by pediatricians were associated with same-day HPV
      vaccination of 11- to 12-year-olds by evaluating audio recordings of visits.
      METHODS: Verilogue, a market research company maintaining a panel of primary care
      pediatricians, provided audio recordings and transcriptions of well-child visits
      for 11- to 12-year-old patients from January through June 2013. Seventy-five
      transcripts from 19 pediatricians were coded for use of presumptive language
      (i.e., words conveying assumption of vaccine delivery), offer of delay,
      recommendation strength, and information provision. Using logistic regression, we
      evaluated the association between pediatrician communication approaches and
      agreement to same-day HPV vaccination. Generalized estimating equations accounted
      for clustering of patients within pediatricians. RESULTS: Same-day agreement to
      HPV vaccination occurred in 29% of encounters. Pediatricians in the sample often
      provided parents with inconsistent, mixed messages and sometimes offered
      information about HPV or HPV vaccination that was inaccurate. Pediatricians used
      presumptive language in only 11 of 75 encounters; when used, presumptive language
      was associated with higher odds of accepting HPV vaccine (73% vs. 22%; odds ratio
      = 8.96; 95% confidence interval = 2.32-34.70). Pediatricians offered or
      recommended delay in most encounters (65%). HPV vaccine acceptance occurred far
      more often when pediatricians did not mention delaying vaccination (82% vs. 6%;
      odds ratio = 80.84; 95% confidence interval = 15.72-415.67). Same-day vaccination
      was not associated with strength of recommendation or pediatrician reference to
      vaccinating their own children. CONCLUSIONS: Our findings highlight the need to
      develop and evaluate physician-focused trainings on using presumptive language
      for same-day HPV vaccination.

PMID- 28455128
TI  - Burden of Adult Community-acquired, Health-care-Associated, Hospital-Acquired,
      and Ventilator-Associated Pneumonia: New York City, 2010 to 2014.
AB  - BACKGROUND: Although pneumonia is a leading cause of death in New York City
      (NYC), limited data exist about the settings in which pneumonia is acquired
      across NYC. Cases of pneumonia acquired in community settings are more likely to
      be preventable with vaccines and treatable with first-line antibiotics than those
      acquired in noncommunity settings. The objective of this study was to estimate
      the burden of hospitalizations associated with community-acquired (CAP), health
      care-associated (HCAP), hospital-acquired (HAP), and ventilator-associated (VAP)
      pneumonia from 2010 to 2014. METHODS: This retrospective analysis was performed
      by using an all-payer reporting system of hospital discharges that included NYC
      residents aged >= 18 years. Pneumonia-associated hospitalizations were defined as
      any hospitalization that included a diagnostic code for pneumonia among any of
      the discharge diagnoses. Using published clinical guidelines, we classified
      hospitalizations into mutually exclusive categories of CAP, HCAP, HAP, and VAP
      and defined pneumonia acquired in the community setting as the combination of CAP
      and HCAP. RESULTS: Of 4,614,108 hospitalizations during the reporting period,
      283,927 (6.2%) involved pneumonia. Among pneumonia-associated hospitalizations,
      154,158 (54.3%) were CAP, 85,656 (30.2%) were HCAP, 39,712 (14.0%) were HAP, and
      4,401 (1.6%) were VAP. Death during hospitalization occurred in 7.9% of CAP
      associated hospitalizations, compared with 15.6% of HCAP-associated
      hospitalizations, 20.7% of HAP-associated hospitalizations, and 21.6% of VAP
      associated hospitalizations. CONCLUSIONS: Most pneumonia-associated
      hospitalizations in NYC involve pneumonias acquired in the community setting.
      Although 15.6% of pneumonia-associated hospitalizations were categorized as HAP
      or VAP, these pneumonias accounted for > 25% of deaths from pneumonia-associated
      hospitalizations. Public health pneumonia prevention efforts need to target both
      community and hospital settings.

PMID- 28455130
TI  - A Nonsurgical Approach to Adolescent Breast Asymmetry Using External Prostheses.
AB  - PURPOSE: Currently, there are few nonsurgical treatment options for pediatric
      patients with developmental breast asymmetry. Our group established a partnership
      with a prosthetic unit within a local oncology center to provide custom-fit
      breast prostheses for young women with breast asymmetry. The purpose of this
      study was to describe the effect of this experience on patients' self-esteem and
      body image. METHODS: Patients were administered an anonymous satisfaction survey
      at least 1 month after their first fitting at the prosthetic unit. The survey was
      designed to evaluate body image, self-esteem, as well as social and emotional
      well-being before and after treatment. Thematic analysis was used to assess their
      experiences. RESULTS: Seventeen patients, aged 12-19 years, visited the
      prosthetic unit and subsequently completed the retrospective survey. After using
      the breast prostheses, 14 (82.4%) patients reported an improvement in body image
      and 12 (70.6%) patients reported an improvement in self-esteem. Benefits
      pertaining to three emergent themes were revealed: "body wholeness/symmetry,"
      "body image and psychological well-being," and "esthetic outcome." CONCLUSIONS:
      Results from the survey demonstrate the ease and efficacy of a form of
      nonsurgical treatment for adolescent breast asymmetry. Our partnership with an
      adult oncology center can serve as a national model to support the development of
      similar treatment programs. Existing resources that have been previously used
      only for adult breast cancer survivors can be effectively applied to the
      adolescent population to ameliorate the negative psychological effects of breast
      asymmetry.

PMID- 28455131
TI  - Echocardiographic pulmonary artery pressure estimation and heart failure
      rehospitalization burden in patients with acute heart failure.
AB  - : Pulmonary hypertension (PH) is a strong predictor of mortality in patients with
      heart failure (HF). However, the relationship between PH, through
      echocardiographic pulmonary artery pressure (PASP) estimation, and the risk of HF
      rehospitalizations remains unclear. METHODS: We prospectively included 2343
      consecutive patients discharged for acute heart failure (AHF). PH was estimated
      by echocardiography through PASP determination during the index admission.
      Patients were categorized as follows across PASP: non-measurable, normal
      (<=35mmHg), mild (36-45mmHg), moderate (46-60mmHg), or severe PH (>60mmHg).
      Negative binomial regression method was used to evaluate the association between
      PASP and recurrent HF hospitalizations across preserved (HFpEF: >=50%), mid-range
      (HFmrEF: 40-49%) and reduced ejection fraction (HFrEF: <40%). RESULTS: Mean age
      of the cohort was 72.8+/-11.2years, 1187 (50.5%) were women, and 1252 (53.4%) and
      410 (17.5%) showed HFpEF and HFmrEF, respectively. At a median (interquartile
      range) follow-up of 2.3 (0.8-4.5) years, we registered 1114 (47.6%) deaths, and
      1834 HF-related rehospitalizations in 943 (40.2%) patients. After multivariable
      adjustment, and compared to patients with normal PASP, severe PH exhibited an
      independent higher risk of recurrent HF admissions only in HFpEF (IRR=1.66; 95%
      confidence interval (CI), 1.16-2.38; p=0.005), whereas in HFmrEF patients there
      was a non-significant trend to higher HF readmissions (IRR: 1.73; 95% CI, 0.85
      3.55; p=0.132). Severe PH was not related with recurrent hospitalizations in
      HFrEF (IRR: 1.19; 95% CI, 0.66-2.14; p=0.553). CONCLUSIONS: Echocardiography
      derived PASP evaluated during an episode of AHF is related to HF readmission
      burden, particularly in those patients with HFpEF.

PMID- 28455132
TI  - Garcinia mangostana pericarp extract protects against oxidative stress and
      cardiovascular remodeling via suppression of p47phox and iNOS in nitric oxide
      deficient rats.
AB  - Nomega-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension and
      cardiovascular remodeling are associated with oxidative stress and inflammation.
      Garcinia mangostana Linn., has been reported to have antioxidant and anti
      inflammatory properties. This study investigated whether G. mangostana pericarp
      extract (GME) could prevent l-NAME-induced hemodynamic alterations,
      cardiovascular remodeling, oxidative stress and inflammation in rats. Male
      Sprague-Dawley rats were given 40mg/kg/day of l-NAME in drinking water to induce
      hypertension, and were simultaneously treated with GME at a dose of 200mg/kg/day.
      Rats that received l-NAME for five weeks had high blood pressure, left
      ventricular hypertrophy and thickening of aortic wall. Vascular superoxide
      production, plasma malondialdehyde (MDA), and plasma tumor necrosis factor alpha
      (TNF-alpha) were significantly increased in l-NAME-hypertensive rats (p<0.05).
      This was consistent with up-regulation of the p47phox NADPH oxidase subunit and
      iNOS protein expression in aortic tissues (p<0.05). Low levels of plasma nitric
      oxide metabolites were observed in l-NAME hypertension. GME prevented the
      development of hypertension and cardiovascular remodeling induced by l-NAME with
      reduced oxidative stress and inflammation. These data suggest that GME had a
      protective effect against l-NAME-induced hypertension and cardiovascular
      remodeling via suppressing p47phox NADPH oxidase subunit and iNOS protein
      expression resulting in enhancing NO bioavailability.

PMID- 28455133
TI  - Development and application of a quantitative PCR assay to study equine
      herpesvirus 5 invasion and replication in equine tissues in vitro and in vivo.
AB  - Equine herpesvirus 5 (EHV-5) infection is associated with pulmonary fibrosis in
      horses, but further studies on EHV-5 persistence in equine cells are needed to
      fully understand viral and host contributions to disease pathogenesis. Our aim
      was to develop a quantitative PCR (qPCR) assay to measure EHV-5 viral copy number
      in equine cell cultures, blood lymphocytes, and nasal swabs of horses.
      Furthermore, we used a recently developed equine primary respiratory cell culture
      system to study EHV-5 pathogenesis at the respiratory tract. PCR primers and a
      probe were designed to target gene E11 of the EHV-5 genome. Sensitivity and
      repeatability were established, and specificity was verified by testing multiple
      isolates of EHV-5, as well as DNA from other equine herpesviruses. Four-week old
      fully differentiated (mature), newly seeded (immature) primary equine respiratory
      epithelial cell (ERECs), and equine dermal cell cultures were inoculated with EHV
      5 and the cells and supernatants collected daily for 14days. Blood lymphocytes
      and nasal swabs were collected from horses experimentally infected with equine
      herpesvirus 1 (EHV-1). The qPCR assay detected EHV-5 at stable concentrations
      throughout 14days in inoculated mature EREC and equine dermal cell cultures
      (peaking at 202 and 5861 viral genomes per 106 cellular beta actin,
      respectively). EHV-5 copies detected in the immature EREC cultures increased over
      14days and reached levels greater than 10,000 viral genomes per 106 cellular beta
      actin. Moreover, EHV-5 was detected in the lymphocytes of 76% of horses and in
      the nasal swabs of 84% of horses experimentally infected with EHV-1 pre
      inoculation with EHV-1. Post-inoculation with EHV-1, EHV-5 was detected in
      lymphocytes of 52% of horses while EHV-5 levels in nasal swabs were not
      significantly different from pre-inoculation levels. In conclusion, qPCR was a
      reliable technique to investigate viral load in in vivo and in vitro samples, and
      EHV-5 replication in equine epithelial cells may be influenced by cellular stages
      of differentiation.

PMID- 28455134
TI  - Cyclodextrin nanosystems in oral drug delivery: A mini review.
AB  - Oral delivery of many therapeutic agents remains challenging due to gastric
      insolubility/poor dissolution, inefficient intestinal permeability and pre
      systemic inactivation. These problems limit the advantages of convenience and
      increased compliance they provide in the therapy of many chronic diseases.
      Cyclodextrin nanosystems have emerged as promising platforms for drug-specific
      construction of the oral delivery nanosystems able to optimize the desired
      physicochemical properties and pharmacokinetic parameters; without a compromise
      on safety. This review focuses on some recent and encouraging advances in the
      application of cyclodextrin nanosystems for oral drug delivery. A general
      overview of cyclodextrins and pharmaceutical nanotechnology in oral delivery
      systems is provided. Some of the strategies being exploited for the synthesis of
      these nanosystems, and their potential for the intelligent navigation of the
      gastrointestinal tract for optimal bioavailability and biodistribution are then
      illustrated. Perspectives for translating these nanosystems from laboratory
      efficient formulations to clinically useful medicines are also discussed.

PMID- 28455135
TI  - SN38 conjugated hyaluronic acid gold nanoparticles as a novel system against
      metastatic colon cancer cells.
AB  - Combination of chemotherapy and photothermal therapy has been proposed for better
      treatment of metastatic colon cancer. In this study SN38, a highly potent
      cytotoxic agent, was conjugated to negatively charged hyaluronic acid (HA), which
      was deposited on the surface of the positively charged gold nanoparticles via
      electrostatic interaction. The drug conjugation and its interaction with gold
      nanoparticles were verified by 1H NMR and UV-vis spectroscopies, respectively.
      The prepared SN38-HA gold NPs are negatively charged spherical nanoparticles with
      an average size of 75+/-10nm. In vitro release study revealed that drug release
      in acidic conditions (pH 5.2) was faster than that in physiological pH. Red light
      emitting diode (LED, 630nm, 30mW) was used as a light source for photothermal
      experiments. The drug release in acidic conditions was increased up to 30% using
      red LED illumination (6min) in comparison with experiment carried out indark. The
      cytotoxicity study on MUC1 positive HT29, SW480 colon cancer cells and MUC1
      negative CHO cells, showed higher toxicity of the nanoparticles on HT29 and SW480
      cell lines compared to CHO cells. Confocal microscopy images along with flow
      cytometry analysis confirm the cytotoxicity results. The incubation time for
      reaching IC50 decreases from 48h to 24h by LED illumination after nanoparticle
      treatment. Migratory potential of the HT29 and SW480 cell lines was reduced by co
      application of SN38-HA gold NPs and LED radiation. Also anti-proliferative study
      indicates that LED radiation has increased the cytotoxicity of the nanoparticles
      and this effect is remained up to 8days.

PMID- 28455136
TI  - In vivo distribution of zoledronic acid in a bisphosphonate-metal complex-based
      nanoparticle formulation synthesized by a reverse microemulsion method.
AB  - Bisphosphonates are used to treat bone diseases such as osteoporosis and cancer
      induced bone pain and fractures. It is thought that modifying the
      pharmacokinetics and biodistribution profiles of bisphosphonates (i.e. rapid
      renal clearance and extensive bone absorption) will not only reduce their side
      effects, but also expand their clinical applications to extraskeletal tissues. In
      the present work, using zoledronic acid (Zol) and calcium as model bisphosphonate
      and metal molecules, respectively, we prepared DOPA (an anionic lipid)-coated
      spherical Zol-Ca nanocomposites (Zol-Ca@DOPA) and developed Zol-nanoparticle
      formulations (i.e. Zol-Ca@bi-lipid NPs) based on the nanocomposites. The
      influence of the inputted weight ratio of Zol-Ca@DOPA to DSPE-PEG2k on the
      properties (e.g. size, size distribution, loading efficiency, encapsulation
      efficiency, zeta potential, and polydispersity) of Zol-Ca@bi-lipid NPs was
      investigated, and a type of Zol-Ca@bi-lipid NPs with size around 25nm was
      selected for further studies. In a mouse model, the Zol-Ca@bi-lipid NPs
      significantly reduced the bone distribution of Zol, increased the blood
      circulating time of Zol, and altered the distribution of Zol in major organs, as
      compared to free Zol. It is expected that similar nanoparticles prepared with
      bisphosphonate-metal complexes can be explored to expand the applications to
      bisphosphonates in extraskeletal tissues.

PMID- 28455137
TI  - Influence of static magnetic field exposure on fatty acid composition in
      Salmonella Hadar.
AB  - We have been interested, in this work, to investigate the effect of the exposure
      to static magnetic field at 200 mT (SMF) on the fatty acid (FA) composition of
      Salmonella enterica subsp Enterica serovar Hadar isolate 287: effects on the
      proportion of saturated and unsaturated fatty acids (SFAs, UFAs), cyclopropane
      fatty acids (CFAs) and hydroxy fatty acids after exposure to the static magnetic
      field at 200 mT (SMF). Analysis with Gas Chromatography-Mass Spectrometry (GC-MS)
      of total lipid showed that the proportion of the most fatty acids was clearly
      affected. The comparison of UFAs/SFAs ratio in exposed bacteria and controls
      showed a diminution after 3 and 6 h of exposure. This ration reached a balance
      after 9 h of treatment with SMF. So we can conclude that S. Hadar tries to adapt
      to magnetic stress by changing the proportions of SFAs and UFAs over time to
      maintain an equilibrium after 9 h of exposure, thus to maintain the inner
      membranes fluidity. Also, a decrease in the proportion of hydroxy FAs was
      observed after 6 h but an increase of this proportion after 9 h of exposure.
      Concerning CFAs, its proportion raised after 6 h of exposure to the SMF but it
      decreased after 9 h of exposure. These results are strongly correlated with those
      of cfa (cyclopropane fatty acid synthase) gene expression which showed a decrease
      of its expression after 9 h of exposure.

PMID- 28455138
TI  - Evaluation of Merkel cell polyomavirus in non-small cell lung cancer and adjacent
      normal cells.
AB  - Several risk factors have been linked to lung cancer (LC). Nevertheless, a viral
      etiology has been mentioned for a subset of patients developing LC. The aim of
      this study was to evaluate the effect of Merkel cell polyomavirus (MCPyV) on
      developing non-small cell lung cancer (NSCLCs). In total, 96 paraffin-embedded
      NSCLC biopsies and 96 adjacent non-LC normal specimens were analyzed by
      quantitative real-time polymerase chain reaction (PCR) for the existence of the
      MCPyV DNA and the expressions of RNA transcripts. Among the 96 enrolled
      participants, 42 patients were adenocarcinomas (ADs) and 54 patients were
      squamous cell carcinoma (SCC). Of the 42 ADs, MCPyV DNA was determined in 15
      (35.7%) samples and of the 54 SCC, MCPyV DNA was detected in 22 (40.7%) samples.
      Only one non-cancerous sample in SCC subjects was positive for MCPyV LT-Ag DNA
      load (0.216 * 10-3). In MCPyV-positive subjects, the median MCPyV copy number was
      higher in the patients with ADs (0.016 * 10-3 copies/cell) compared to SCCs
      (0.005 * 10-3 copies/cell); but this difference was not statistically significant
      (P = 0.913). In the seven stages of LC, the MCPyV LT-Ag was quantified in stage
      IV (0.204 * 10-3 copies/cell) more than in other stages. There was statistically
      significant difference between stages of cancer and MCPyV LT-Ag DNA load (P =
      0.002). These results revealed for the first time the presence of MCPyV in a
      subset of patients with NSCLCs in Iran. Further studies should be carried out to
      clarify the role of MCPyV in lung carcinogenesis.

PMID- 28455140
TI  - [Systemic corticosteroids during acute COPD exacerbations].

PMID- 28455139
TI  - Evaluation of Adenovirus-36 (Ad-36) antibody seropositivity and adipokine levels
      in obese children.
AB  - Adenovirus 36 (Ad-36) has recently been suggested as a possible contributor to
      the current obesity epidemic. The aim of this study was to investigate the
      prevalence of Ad-36 antibodies in obese children, as well as investigate the role
      of serum leptin and lipid levels in Ad-36-obesity. Seventy-one obese children and
      62 non-obese children were included as the patient group (PG), including the
      healthy control group (HCG), respectively. Simultaneously, Ad-36 antibodies and
      adipokine levels were assessed with serum neutralization assays (SNA) and ELISA.
      Ad-36 antibody was detected in 9 patients (12.7%) and 1 patient (1.6%) in both
      the PG and HCG, respectively, while a significant difference was detected between
      groups (p < 0.05). Although serum LDL, total cholesterol, triglycerides and
      leptin levels were detected significantly higher, adiponectin level was detected
      paradoxically lower in the PG. However, a significant difference was not detected
      for lipids and leptin levels; adiponectin levels were found to be significantly
      lower in Ad-36 antibody-positive PG (p < 0.05). In conclusion, we suggest there
      is an association between Ad-36 and obesity in children, including IL-6 levels
      increasing in obese children with Ad-36 seropositivity. Conversely, adiponectin
      levels in obese children with Ad-36 seropositivity were higher. As such, there is
      a need for studies to understand the mechanisms underlying this observation.

PMID- 28455141
TI  - Identification of potential therapeutic compounds for Parkinson's disease using
      Drosophila and human cell models.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      after Alzheimer's disease. It is caused by a loss of dopaminergic neurons in the
      substantia nigra pars compacta, leading to a decrease in dopamine levels in the
      striatum and thus producing movement impairment. Major physiological causes of
      neurodegeneration in PD are oxidative stress (OS) and mitochondrial dysfunction;
      these pathophysiological changes can be caused by both genetic and environmental
      factors. Although most PD cases are sporadic, it has been shown that 5-10% of
      them are familial forms caused by mutations in certain genes. One of these genes
      is the DJ-1 oncogene, which is involved in an early-onset recessive PD form.
      Currently, PD is an incurable disease for which existing therapies are not
      sufficiently effective to counteract or delay the progression of the disease.
      Therefore, the discovery of alternative drugs for the treatment of PD is
      essential. In this study we used a Drosophila PD model to identify candidate
      compounds with therapeutic potential for this disease. These flies carry a loss
      of-function mutation in the DJ-1beta gene, the Drosophila ortholog of human DJ-1,
      and show locomotor defects reflected by a reduced climbing ability. A pilot
      modifier chemical screen was performed, and several candidate compounds were
      identified based on their ability to improve locomotor activity of PD model
      flies. We demonstrated that some of them were also able to reduce OS levels in
      these flies. To validate the compounds identified in the Drosophila screen, a
      human cell PD model was generated by knocking down DJ-1 function in SH-SY5Y
      neuroblastoma cells. Our results showed that some of the compounds were also able
      to increase the viability of the DJ-1-deficient cells subjected to OS, thus
      supporting the use of Drosophila for PD drug discovery. Interestingly, some of
      them have been previously proposed as alternative therapies for PD or tested in
      clinical trials and others are first suggested in this study as potential drugs
      for the treatment of this disease.

PMID- 28455142
TI  - A fish oil diet induces mitochondrial uncoupling and mitochondrial unfolded
      protein response in epididymal white adipose tissue of mice.
AB  - White adipose tissue (WAT) mitochondrial dysfunction is linked to the
      pathogenesis of obesity driven insulin resistance. Dietary conditions that alter
      fat mass are known to affect white adipocyte mitochondrial function, however, the
      impact of high calorie diets on white adipocyte mitochondria is not fully
      understood. The aim of this study is to assess the effect of a diet rich in
      saturated or polyunsaturated fat on mitochondrial unfolded protein response
      (UPRmt), a retrograde signaling response that maintains mitochondrial
      homeostasis, in epididymal WAT (eWAT). Mice were fed a low fat diet (LFD),
      saturated fat diet (SFD) or fish oil (unsaturated fat diet, UFD) and assessed
      changes in eWAT mitochondria. Compared to mice fed a LFD, SFD-fed mice have
      reduced mitochondrial biogenesis markers, mitochondrial fatty acid oxidation
      enzymes and TCA cycle enzymes, suggesting an impaired mitochondrial function that
      could contribute to increased fat mass. In contrast, isocaloric UFD-fed mice have
      increased expression of mitochondrial uncoupling protein 1 (UCP1) and peroxisomal
      fatty acid oxidation enzymes suggesting that elevated mitochondrial uncoupling
      and peroxisomal fatty acid oxidation could contribute to the reduction in fat
      mass. Interestingly, expression of UPRmt-associated proteins caseinolytic
      peptidase (ClpP) and heat shock protein 60 (Hsp60) are induced by UFD, whereas
      SFD reduced the expression of ClpP. Based on our data, we propose that induction
      of UPRmt helps to preserve a functional mitochondria and efficient utilization of
      fat by UFD whereas a dampened UPRmt response might impair mitochondrial function
      and promote fat accumulation by SFD. Thus, our findings suggest a potential role
      of UPRmt in mediating the beneficial effects of fish oil.

PMID- 28455143
TI  - IRE1alpha links Nck1 deficiency to attenuated PTP1B expression in HepG2 cells.
AB  - PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine
      phosphatase superfamily, plays a key role in regulating intracellular signaling
      from various receptor and non-receptor protein tyrosine kinases. Previously, we
      reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells
      enhances basal and growth factor-induced activation of the PI3K-Akt pathway
      through attenuating PTP1B expression. However, the underlying mechanism by which
      Nck1 depletion represses PTP1B expression remains unclear. In this study, we
      found that silencing Nck1 attenuates PTP1B expression in HepG2 cells through down
      regulation of IRE1alpha. Indeed, we show that silencing Nck1 in HepG2 cells leads
      to decreased IRE1alpha expression and signaling. Accordingly, IRE1alpha depletion
      using siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor
      induced Akt activation, reproducing the effects of silencing Nck1 on activation
      of this pathway. In addition, depletion of IRE1alpha also leads to reduced PTP1B
      expression, which was rescued by ectopic expression of IRE1alpha in Nck1-depleted
      cells. Mechanistically, we found that silencing either Nck1 or IRE1alpha in HepG2
      cells decreases PTP1B mRNA levels and stability. However, despite miR-122 levels,
      a miRNA targeting PTP1B 3' UTR and inducing PTP1B mRNA degradation in HepG2
      cells, are increased in both Nck1- and IRE1alpha-depleted HepG2 cells, a miR-122
      antagomir did not rescue PTP1B expression in these cells. Overall, this study
      highlights an important role for Nck1 in fine-tuning IRE1alpha expression and
      signaling that regulate PTP1B expression and subsequent activation of the PI3K
      Akt pathway in HepG2 cells.

PMID- 28455144
TI  - Identification of NCK1 as a novel downstream effector of STAT3 in colorectal
      cancer metastasis and angiogenesis.
AB  - Signal transducer and activator of transcription 3 (STAT3) is known to activate
      targets associated with invasion, proliferation, and angiogenesis in a wide
      variety of cancers. The adaptor protein NCK1 is involved in cytoskeletal movement
      and was identified as a STAT3-associated target in human tumors. However, the
      underlying molecular mechanism associated with colorectal cancer (CRC) metastasis
      is not yet completely understood. In this study, we report a novel STAT3 to NCK1
      signaling pathway in colorectal cancer (CRC). We investigated the expression of
      NCK1 and its potential clinical and biological significance in CRC. NCK1 was
      noticeably up-regulated in human CRC tissues. NCK1 was also significantly
      associated with serosal invasion, lymph metastasis, and tumor-node-metastasis
      classification but was inversely correlated with differentiation. Gain-of
      function and loss-of-function studies have shown that ectopic expression of NCK1
      enhanced metastasis and angiogenesis in CRC cells. By gene expression analyses,
      we revealed a high co-overexpression of STAT3 and NCK1 in CRC tissues. Ectopic
      overexpression of STAT3 in CRC cells induced the expression of NCK1, whereas
      STAT3 knockdown decreased the expression of NCK1. Promoter activation and binding
      analyses demonstrated that STAT3 promoted the expression of NCK1 via direct
      action on the NCK1 promoter. The knock down of NCK1 partially reduced the CRC
      cell metastasis and angiogenesis promoted by STAT3. Additionally, by co
      immunoprecipitation assays, we verified that NCK1 interacted with PAK1, which
      resulted in the activation of the PAK1/ERK pathway. STAT3 induced the
      transcription of NCK1 and triggered a PAK1/ERK cascade in CRC. These findings
      suggest a novel STAT3 to NCK1 to PAK1/ERK signaling mechanism that is potentially
      critical for CRC metastasis and angiogenesis.

PMID- 28455145
TI  - Managing expense and expectation in a treatment revolution: Problematizing
      prioritisation through an exploration of hepatitis C treatment 'benefit'.
AB  - BACKGROUND: Direct-acting antivirals (DAAs) have transformed the hepatitis C
      (HCV) treatment landscape. These highly effective drugs are, however, not
      available to all. In a context of DAA rationing, clinicians are advised to
      "manage patient expectations" about the benefits of a HCV cure. This directive
      particularly pertains to people with minimal liver damage and those who have
      ceased injecting: populations negated in contemporary prioritisation debates.
      METHODS: This paper engages with the assumptions underpinning HCV treatment
      prioritisation discourses to explore the concept of treatment 'benefit' from
      patient perspectives. Data are from a qualitative longitudinal study exploring
      treatment transitions and decision-making from 2012-2015. Participants comprised
      28 people living with HCV, ten treatment providers and eight stakeholders, based
      in London, United Kingdom (UK). One hundred hours of clinic observations were
      conducted at two HCV treatment hospitals. Thematic analyses pertaining to
      treatment expectation and outcome inform this paper. RESULTS: Twenty-two
      participants commenced treatment. The majority who were unable to access DAAs
      chose to commence interferon-based treatment immediately rather than wait.
      Participants accounted for treatment urgency in relation to three interrelated
      narratives of hope and expectation. HCV treatment promised: social reconnection;
      social redemption and a return to 'normality'. For many with successful treatment
      outcomes, these benefits appeared to be realised. CONCLUSION: The DAA era heralds
      a discursive shift: from 'managing [interferon] risk and difficulty' to 'managing
      [DAA] expense and expectation'. Calls to 'manage patient expectations' about the
      benefits of HCV cure are predicated on clinical benefits only, negating the
      social impacts of living with HCV. The public health priorities commonly
      articulated in treatment prioritisation debates are not consistent with those of
      people managing illness in their daily lives. During this 'treatment revolution'
      there is a need to be cognisant of the multiple publics living with the virus and
      the treatment needs of those who do not fit population-health scenarios.

PMID- 28455146
TI  - Detection of Anomalous Cervical Internal Carotid Artery Branches by Colour Duplex
      Ultrasound.
AB  - OBJECTIVES: Conventional anatomical descriptions of the cervical internal carotid
      artery (ICA) report that no branches arise from this segment. However reports of
      ICA branches exist. The study aim was to determine the prevalence of anomalous
      branches of the ICA using colour duplex ultrasound (CDU). METHODS: Four hundred
      consecutive patients (800 carotid vessels) referred to a tertiary hospital
      vascular laboratory for investigation of carotid disease were included. A clear
      differentiation of a low resistive ICA and a high resistive external carotid
      artery (ECA) waveform was required. CDU was performed on a Philips IU22
      ultrasound system with a 9-3 MHz linear array transducer employing a standard
      carotid imaging protocol. The origin of each ICA branch was identified using B
      mode and CDU. Anatomical orientation of ICA branches and distance from
      bifurcation was recorded and spectral CDU analysis was performed. RESULTS: Twenty
      ICA branches, tracking cephaladly, were detected in 16 patients (4%), or 2.5%
      (20/800) vessels. The median age was 73 years; 50% were female and 50% male. All
      patients demonstrated a single branch [unilateral anomaly (n = 12 patients),
      bilateral anomaly (n = 4) patients]. Eighty-five percent arose from the posterior
      wall of the ICA. The median distance from ICA bifurcation was 4 mm (range 0-18
      mm). ICA branch diameters ranged from 1.2 mm to 2.4 mm (median 1.4 mm, mean 1.6
      mm). Eighty percent of ICA branches had less than 50% stenosis. Spectral analysis
      revealed high resistive waveforms in all branches. CONCLUSIONS: Branches from the
      ICA exist and can be characterised with CDU. Prevalence in a tertiary hospital
      referral cohort is 4%. Given their potential clinical implications, standard
      carotid imaging protocols should consider routine assessment and reporting of ICA
      branches.

PMID- 28455147
TI  - Thresholds in women with abdominal aortic aneurysm.

PMID- 28455149
TI  - Patterns of Care and Treatment Outcomes of Elderly Patients with Stage I
      Esophageal Cancer: Analysis of the National Cancer Data Base.
AB  - INTRODUCTION: This study analyzes practice patterns, treatment-related mortality,
      survival, and predictors thereof in elderly patients with early-stage esophageal
      cancer (EC). METHODS: The National Cancer Data Base was queried for cT1-2 N0 EC
      in patients 80 years of age and older. Patients were divided into four treatment
      groups: observation (Obs), chemoradiotherapy (CRT), local excision (LE), and
      esophagectomy (Eso). Patient, tumor, and treatment parameters were extracted and
      compared. Analyses were performed on overall survival (OS) and postoperative 30-
      and 90-day mortality. RESULTS: A total of 923 patients from 2004 to 2012 were
      analyzed. Of these, 43% underwent clinical Obs, 22% underwent CRT, 25% underwent
      LE, and 10% underwent Eso. Patients undergoing Obs were older, had more
      comorbidities, were treated at nonacademic centers, and lived 25 miles or less
      from the facility. Patients receiving an operation (Eso or LE) were more often
      younger, male, white, and in the top income quartile. The postoperative 30-day
      mortality rates in the LE and Eso groups were 1.3% and 9.6%, respectively (p <
      0.001) and increased to 2.6% and 20.2% at 90 days, respectively (p < 0.001). The
      5-year OS rate was 7% for Obs, 20% for CRT, 33% for LE, and 45% for Eso (p <
      0.001). Multivariate analyses showed improved OS with any local definitive
      therapy: CRT (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.34-0.52,
      p < 0.001), LE (HR = 0.3, 95% CI: 0.24-0.38, p < 0.001), and Eso (HR = 0.32, 95%
      CI: 0.23-0.44, p < 0.001). CONCLUSIONS: There are noteworthy demographic,
      socioeconomic, and regional disparities influencing management of elderly
      patients with stage I EC. Despite high rates of Obs, careful consideration of all
      local therapy options is warranted, given the improved outcomes with treatment.

PMID- 28455148
TI  - Morphological suitability for endovascular repair, non-intervention rates, and
      operative mortality in women and men assessed for intact abdominal aortic
      aneurysm repair: systematic reviews with meta-analysis.
AB  - BACKGROUND: Prognosis for women with abdominal aortic aneurysm might be worse
      than the prognosis for men. We aimed to systematically quantify the differences
      in outcomes between men and women being assessed for repair of intact abdominal
      aortic aneurysm using data from study periods after the year 2000. METHODS: In
      these systematic reviews and meta-analysis, we identified studies (randomised,
      cohort, or cross-sectional) by searching MEDLINE, Embase, CENTRAL, and grey
      literature published between Jan 1, 2005, and Sept 2, 2016, for two systematic
      reviews and Jan 1, 2009, and Sept 2, 2016, for one systematic review. Studies
      were included if they were of both men and women, with data presented for each
      sex separately, with abdominal aortic aneurysms being assessed for aneurysm
      repair by either endovascular repair (EVAR) or open repair. We conducted three
      reviews based on whether studies reported the proportion morphologically suitable
      (within manufacturers' instructions for use) for EVAR (EVAR suitability review),
      non-intervention rates (non-intervention review), and 30-day mortality (operative
      mortality review) after intact aneurysm repair. Studies had to include at least
      20 women (for the EVAR suitability review), 20 women (for the non-intervention
      review), and 50 women (for the operative mortality review). Studies were excluded
      if they were review articles, editorials, letters, or case reports. For the
      operative review, studies were also excluded if they only provided hazard ratios
      or only reported in-hospital mortality. We assessed the quality of the studies
      using the Newcastle-Ottawa scoring system, and contacted authors for the
      provision of additional data if needed. We combined results across studies by
      random-effects meta-analysis. This study is registered with PROSPERO, number
      CRD42016043227. FINDINGS: Five studies assessed the morphological eligibility for
      EVAR (1507 men, 400 women). The overall pooled proportion of women eligible (34%)
      for EVAR was lower than it was in men (54%; odds ratio [OR] 0.44, 95% CI 0.32
      0.62). Four single-centre studies reported non-intervention rates (1365 men, 247
      women). The overall pooled non-intervention rates were higher in women (34%) than
      men (19%; OR 2.27, 95% CI 1.21-4.23). The review of 30-day mortality included
      nine studies (52 018 men, 11 076 women). The overall pooled estimate for EVAR was
      higher in women (2.3%) than in men (1.4%; OR 1.67, 95% CI 1.38-2.04). The overall
      estimate for open repair also was higher in women (5.4%) than in men (2.8%; OR
      1.76, 95% CI 1.35-2.30). INTERPRETATION: Compared with men, a smaller proportion
      of women are eligible for EVAR, a higher proportion of women are not offered
      intervention, and operative mortality is much higher in women for both EVAR and
      open repair. The management of abdominal aortic aneurysm in women needs
      improvement. FUNDING: National Institute for Health Research (UK).

PMID- 28455150
TI  - Evaluation of a rule-based method for epidemiological document classification
      towards the automation of systematic reviews.
AB  - INTRODUCTION: Most data extraction efforts in epidemiology are focused on
      obtaining targeted information from clinical trials. In contrast, limited
      research has been conducted on the identification of information from
      observational studies, a major source for human evidence in many fields,
      including environmental health. The recognition of key epidemiological
      information (e.g., exposures) through text mining techniques can assist in the
      automation of systematic reviews and other evidence summaries. METHOD: We
      designed and applied a knowledge-driven, rule-based approach to identify targeted
      information (study design, participant population, exposure, outcome, confounding
      factors, and the country where the study was conducted) from abstracts of
      epidemiological studies included in several systematic reviews of environmental
      health exposures. The rules were based on common syntactical patterns observed in
      text and are thus not specific to any systematic review. To validate the general
      applicability of our approach, we compared the data extracted using our approach
      versus hand curation for 35 epidemiological study abstracts manually selected for
      inclusion in two systematic reviews. RESULTS: The returned F-score, precision,
      and recall ranged from 70% to 98%, 81% to 100%, and 54% to 97%, respectively. The
      highest precision was observed for exposure, outcome and population (100%) while
      recall was best for exposure and study design with 97% and 89%, respectively. The
      lowest recall was observed for the population (54%), which also had the lowest F
      score (70%). CONCLUSION: The generated performance of our text-mining approach
      demonstrated encouraging results for the identification of targeted information
      from observational epidemiological study abstracts related to environmental
      exposures. We have demonstrated that rules based on generic syntactic patterns in
      one corpus can be applied to other observational study design by simple
      interchanging the dictionaries aiming to identify certain characteristics (i.e.,
      outcomes, exposures). At the document level, the recognised information can
      assist in the selection and categorization of studies included in a systematic
      review.

PMID- 28455151
TI  - Symptom severity prediction from neuropsychiatric clinical records: Overview of
      2016 CEGS N-GRID shared tasks Track 2.
AB  - The second track of the CEGS N-GRID 2016 natural language processing shared tasks
      focused on predicting symptom severity from neuropsychiatric clinical records.
      For the first time, initial psychiatric evaluation records have been collected,
      de-identified, annotated and shared with the scientific community. One-hundred
      ten researchers organized in twenty-four teams participated in this track and
      submitted sixty-five system runs for evaluation. The top ten teams each achieved
      an inverse normalized macro-averaged mean absolute error score over 0.80. The top
      performing system employed an ensemble of six different machine learning-based
      classifiers to achieve a score 0.86. The task resulted to be generally easy with
      the exception of two specific classes of records: records with very few but
      crucial positive valence signals, and records describing patients predominantly
      affected by negative rather than positive valence. Those cases proved to be very
      challenging for most of the systems. Further research is required to consider the
      task solved. Overall, the results of this track demonstrate the effectiveness of
      data-driven approaches to the task of symptom severity classification.

PMID- 28455152
TI  - Defining a Leader Role curriculum for radiation oncology: A global Delphi
      consensus study.
AB  - BACKGROUND AND PURPOSE: The need for radiation oncologists and other radiation
      oncology (RO) professionals to lead quality improvement activities and contribute
      to shaping the future of our specialty is self-evident. Leadership knowledge,
      skills and behaviours, like other competencies, can be learned (Blumenthal et
      al., 2012). The objective of this study was to define a globally applicable
      competency set specific to radiation oncology for the CanMEDS Leader Role (Frank
      et al., 2015). METHODS: A modified Delphi consensus process delivering two rounds
      of on-line surveys was used. Participants included trainees, radiation/clinical
      oncologists and other RO team members (radiation therapists, physicists, and
      nurses), professional educators and patients. RESULTS: 72 of 95 (76%) invitees
      from nine countries completed the Round 1 (R1) survey. Of the 72 respondents to
      RI, 70 completed Round 2 (R2) (97%). In R1, 35 items were deemed for 'inclusion'
      and 21 for 'exclusion', leaving 41 'undetermined'. After review of items,
      informed by participant comments, 14 competencies from the 'inclusion' group went
      into the final curriculum; 12 from the 'undetermined' group went to R2. In R2, 6
      items reached consensus for inclusion. CONCLUSION: This process resulted in 20 RO
      Leader Role competencies with apparent global applicability. This is the first
      step towards developing learning, teaching and assessment tools for this
      important area of training.

PMID- 28455153
TI  - Multi-institutional analysis of radiation modality use and postoperative outcomes
      of neoadjuvant chemoradiation for esophageal cancer.
AB  - PURPOSE: Relative radiation dose exposure to vital organs in the thorax could
      influence clinical outcomes in esophageal cancer (EC). We assessed whether the
      type of radiation therapy (RT) modality used was associated with postoperative
      outcomes after neoadjuvant chemoradiation (nCRT). PATIENTS AND METHODS:
      Contemporary data from 580 EC patients treated with nCRT at 3 academic
      institutions from 2007 to 2013 were reviewed. 3D conformal RT (3D), intensity
      modulated RT (IMRT) and proton beam therapy (PBT) were used for 214 (37%), 255
      (44%), and 111 (19%) patients, respectively. Postoperative outcomes included
      pulmonary, GI, cardiac, wound healing complications, length of in-hospital stay
      (LOS), and 90-day postoperative mortality. Cox model fits, and log-rank tests
      both with and without Inverse Probability of treatment Weighting (IPW) were used
      to correct for bias due to non-randomization. RESULTS: RT modality was
      significantly associated with the incidence of pulmonary, cardiac and wound
      complications, which also bore out on multivariate analysis. Mean LOS was also
      significantly associated with treatment modality (13.2days for 3D (95%CI 11.7
      14.7), 11.6days for IMRT (95%CI 10.9-12.7), and 9.3days for PBT (95%CI 8.2-10.3)
      (p<0.0001)). The 90day postoperative mortality rates were 4.2%, 4.3%, and 0.9%,
      respectively, for 3D, IMRT and PBT (p=0.264). CONCLUSIONS: Advanced RT
      technologies (IMRT and PBT) were associated with significantly reduced rate of
      postoperative complications and LOS compared to 3D, with PBT displaying the
      greatest benefit in a number of clinical endpoints. Ongoing prospective
      randomized trial will be needed to validate these results.

PMID- 28455154
TI  - Fetal costello syndrome with neuromuscular spindles excess and p.Gly12Val HRAS
      mutation.
AB  - Costello syndrome (CS) is a rare multiple congenital disorder caused by
      activating germline mutations in HRAS gene and is characterized by coarse facial
      features, severe feeding difficulties, failure to thrive, mild to severe
      intellectual disability, severe postnatal growth retardation, cardiac
      abnormalities or cancer predisposition. Phenotypic spectrum associated with HRAS
      mutations is broad, ranging from attenuated CS phenotype to neonatal and lethal
      forms with limited genotype-phenotype correlations. Congenital myopathy with
      neuromuscular spindle excess has been rarely described in the literature. We
      report a new severe fetal case of CS with distal arthrogryposis due to
      neuromuscular spindle excess, confirmed by the detection of the p.Gly12Val
      mutation in HRAS gene. This case emphasizes the fact that HRAS is the only gene
      responsible for neuromuscular spindle excess, underlines a correlation between
      p.Gly12Val mutation and severe CS phenotype and points out the importance of a
      muscle biopsy performed according to the suitable procedure in neuromuscular
      disorders for any fetal arthrogryposis.

PMID- 28455155
TI  - "Spike" in acute asthma exacerbations during enterovirus D68 epidemic in Japan: A
      nation-wide survey.
AB  - BACKGROUND: In September 2015, Japan experienced an unusual increase in acute
      asthma hospitalizations of children that coincided with an enterovirus D68 (EV
      D68) epidemic. The objective of this study is to investigate whether EV-D68 had a
      causal relationship with the spike in asthma hospitalizations. METHODS: A nation
      wide retrospective survey of asthma hospitalizations of children was performed
      for the period from January 2010 through October 2015. The Japanese Society of
      Pediatric Allergy and Clinical Immunology asked its affiliated hospitals to
      report monthly numbers of hospitalizations, ICU admissions and mechanical
      ventilations due to acute asthma exacerbation. The data were retrieved from
      medical databases using predefined search criteria: diagnosis of asthma or
      asthmatic bronchitis, admission, and age <20 years. Monthly numbers of EV-D68
      detection were also obtained from the Infectious Disease Surveillance Center of
      Japan. A Granger causality test was used to analyze the association of EV-D68
      detections for asthma exacerbation. RESULTS: A total of 157 hospitals reported
      87,189 asthma hospitalizations, including 477 ICU admissions and 1193 mechanical
      ventilations, during the survey period of 5 years and 10 months. The numbers of
      these events increased drastically in September 2015. The Granger causality test
      verified the association between EV-D68 and asthma hospitalizations/mechanical
      ventilations. The most-affected age group was 3-6 years old. CONCLUSIONS: The
      spike in pediatric asthma hospitalizations in Japan in September 2015 was found
      to be associated with the EV-D68 epidemic. Respiratory pathogens can cause
      "epidemics" of asthma exacerbation. Coordinated surveillance of infectious
      diseases and asthma may be beneficial for prevention and better control of both
      illnesses.

PMID- 28455156
TI  - Pentoxifylline increase sperm motility in devitrified spermatozoa from
      asthenozoospermic patient without damage chromatin and DNA integrity.
AB  - The freeze-thaw process results in reduced motility, viability and fertilization
      potential of human spermatozoa. So, a variety of substances were evaluated in
      order to enhance human sperm resistance to the stress of cryopreservation, such
      as Pentoxifylline (PTX) for improving the Intracytoplasmic sperm injection (ICSI)
      outcomes. The aim was to investigate the effect of PTX on sperm parameters and
      chromatin/DNA integrity of asthenozoospermic semen post vitrification. A total of
      30 semen specimens were obtained from infertile men with asthenozoospermia. The
      cryoprotectant-free vitrification was performed for the samples after assessment
      of sperm parameters. After warming, each sample was exposed for 30 min to 3.6
      mmol/l PTX in experimental group and the control group without any treatment
      apposing at 37  degrees C for 30 min in regard, to repeat all in vitro analysis
      (sperm parameters and DNA integrity assay). Regardless of the vitrification
      devastating impacts on sperm parameters, incubation of post vitrified samples
      with PTX increased the rate of progressive motility (P < 0.01). Moreover, PTX
      addition did not significantly damage DNA integrity of asthenozoospermic sperm
      samples. The data showed that PTX was able to improve sperm movement without any
      adverse effects on sperm chromatin/DNA integrity in vitrification program.

PMID- 28455157
TI  - A rare fundal papillary adenofibromatous uterine cyst in a postmenopausal woman:
      A first case report.

PMID- 28455158
TI  - Costs associated with Barrett's esophagus screening in the community: an economic
      analysis of a prospective randomized controlled trial of sedated versus hospital
      unsedated versus mobile community unsedated endoscopy.
AB  - BACKGROUND AND AIMS: Data on the economic impact associated with screening for
      Barrett's esophagus (BE) are limited. As part of a comparative effectiveness
      randomized trial of unsedated transnasal endoscopy (uTNE) and sedated EGD (sEGD),
      we assessed costs associated with BE screening. METHODS: Patients were randomly
      allocated to 3 techniques: sEGD or uTNE in a hospital setting (huTNE) versus uTNE
      in a mobile research van (muTNE). Patients were called 1 and 30 days after
      screening to assess loss of work (because of the screening procedure) and medical
      care sought after procedure. Direct medical costs were extracted from billing
      claims databases. Indirect costs (loss of work for subject and caregiver) were
      estimated using patient reported data. Statistical analyses including
      multivariable analysis accounting for comorbidities were conducted to compare
      costs. RESULTS: Two hundred nine patients were screened (61 sEGD, 72 huTNE, and
      76 muTNE). Thirty-day direct medical costs and indirect costs were significantly
      higher in the sEGD than the huTNE and muTNE groups. Total costs (direct medical +
      indirect costs) were also significantly higher in the sEGD than in the uTNE
      group. The muTNE group had significantly lower costs than the huTNE group.
      Adjustment for age, sex, and comorbidities on multivariable analysis did not
      change this conclusion. CONCLUSIONS: Short-term direct, indirect, and total costs
      of screening are significantly lower with uTNE compared with sEGD. Mobile uTNE
      costs were lower than huTNE costs, raising the possibility of mobile screening as
      a novel method of screening for BE and esophageal adenocarcinoma.

PMID- 28455159
TI  - Metal versus plastic stents for anastomotic biliary strictures after liver
      transplantation: a randomized controlled trial.
AB  - BACKGROUND AND AIMS: Biliary anastomotic stricture occurs in 15% to 20% of
      patients after deceased orthotopic liver transplantation (OLT). It is usually
      treated endoscopically with multiple plastic stents (MPSs), although the use of
      fully covered self-expandable metal stents (cSEMSs) is emerging. This study aims
      to compare the efficacy and safety of cSEMSs versus MPSs in these patients.
      METHODS: A single-center, open-label, randomized clinical trial was performed.
      Patients were randomized to single cSEMSs for 6 months or to MPS placement,
      exchanged every 3 months over 1 year. The primary outcome was stricture
      resolution. Crossover therapy was considered for failure or recurrence. Secondary
      outcomes were sustained improvement, morbidity, and mortality. RESULTS: Between
      October 2009 and January 2014, 162 patients with post-OLT biliary adverse events
      were assessed for eligibility. Sixty-four were prospectively randomized (1:1) to
      cSEMSs or MPSs. Baseline characteristics were comparable. Technical success was
      100%. Median follow-up was 36.4 and 32.9 months for the cSEMS and MPS groups,
      stricture resolution at last stent removal was achieved in 83.3% and 96.5% (P =
      .19), and stricture recurrence was observed in 32% and 0%, respectively (P <
      .01). Adverse events occurred in 23.3% and 6.4% of ERCPs in the cSEMS and MPS
      groups, respectively (P < .01), with 13.3% of acute pancreatitis in the cSEMS
      group and 2.1% in the MPS group (P < .01). CONCLUSIONS: cSEMSs were comparable
      with MPSs regarding post-OLT biliary anastomotic stricture resolution. cSEMSs
      allowed fewer procedures and had a positive effect on cost. Duration of treatment
      with cSEMSs should be further investigated. Sphincterotomy should be considered
      for all patients. (Clinical trial registration number: NCT 01148199.).

PMID- 28455160
TI  - Long-term follow-up results of stepwise radical endoscopic resection for
      Barrett's esophagus with early neoplasia.
AB  - BACKGROUND AND AIMS: Stepwise radical endoscopic resection (SRER) has shown to be
      effective in eradicating Barrett's esophagus (BE) and its associated dysplasia.
      The aim of this study was to assess the long-term durability after successful
      SRER for early Barrett's neoplasia. METHODS: Patients treated with SRER for BE
      <=5 cm with high-grade dysplasia (HGD) or early cancer (EC) and who had reached
      complete eradication of intestinal metaplasia (CE-IM) and neoplasia (CE-neo) were
      included. Primary outcomes were recurrence of neoplasia (HGD/EC), recurrence of
      dysplasia (indefinite for dysplasia included), and recurrence of endoscopically
      visible BE. Secondary outcomes were buried Barrett's glands, IM in biopsy
      specimens obtained distal to a normal-appearing neo-squamocolumnar junction (neo
      SCJ), need for retreatment, and sustained CE-IM and CE-neo at the last follow-up
      endoscopy. RESULTS: Seventy-three patients were included (64 men; mean age, 66
      years; median BE, C2M3). Median follow-up was 76 months. Recurrence of neoplasia
      was observed in 1 patient (T1bN0M0) after 129 months of follow-up and was treated
      with curative surgery (annual incidence of .22% per patient-year of follow-up).
      In 4 patients, recurrence of dysplasia was found (.87% per patient-year of follow
      up). Twelve patients had recurrent endoscopically visible BE after a median
      follow-up of 22 months (2.6% per patient-year of follow-up), mostly small islands
      or tongues. Five patients had a single finding of buried Barrett's glands (1.1%
      per patient-year of follow-up), and 27 patients (5.9% per patient-year of follow
      up) showed IM in biopsy specimens just distal to the neo-SCJ, which was not
      reproduced in 56%. Retreatment was performed in 9 patients. CE-IM and CE-neo
      (excluding IM in the neo-SCJ) at the last follow-up endoscopy was seen in 95% and
      97% of patients, respectively. CONCLUSIONS: This study presents the longest
      published follow-up data on SRER to date. The 6-year outcomes show that
      successful SRER is a durable treatment for BE <=5 cm with HGD/EC.

PMID- 28455161
TI  - Outcomes of screening gastroscopy in first-degree relatives of patients
      fulfilling hereditary diffuse gastric cancer criteria.
AB  - BACKGROUND AND AIMS: The aim of this study was to determine the yield of
      endoscopic screening in first-degree relatives (FDRs) of CDH1-negative hereditary
      diffuse-type gastric cancer (HDGC) patients. METHODS: In this retrospective
      observational cohort study, in 2 expert centers in the Netherlands data were
      collected on FDRs from families fulfilling the international HDGC criteria that
      underwent endoscopic screening. Extensive inspection of the stomach was performed
      by gastroscopy, taking random and/or targeted stomach biopsy specimens to
      identify diffuse-type gastric cancer. RESULTS: Between 2004 and 2016, 90 persons
      (40% men; mean age, 48 years) from 40 families were offered endoscopic screening.
      The mean number of endoscopies per person was 3. The mean follow-up time was 46
      months and mean endoscopic interval 20 months. Signet ring cell carcinoma foci
      restricted to the mucosa (pT1a) were identified in 4 persons (4%) from 1 family,
      which afterward was diagnosed with a germline CTNNA1 mutation. Advanced poorly
      cohesive gastric carcinoma was diagnosed in 1 person from another family.
      Intestinal metaplasia was diagnosed in 38 persons (42%) and low-grade dysplasia
      in 4 persons (4%). Additionally, in 40 persons (44%) scar tissue was observed in
      the gastric mucosa, which can hinder the endoscopic detection of small white
      lesions typical for HDGC. CONCLUSIONS: Endoscopic screening in HDGC families
      without a pathogenic CDH1 mutation may be reasonable, as we detected signet ring
      cell carcinomas in 6% of persons screened. However, the criteria and frequency of
      screening may have to be reconsidered.

PMID- 28455162
TI  - The EPISOD study: long-term outcomes.
AB  - BACKGROUND AND AIMS: The EPISOD (Evaluating Predictors and Interventions in
      Sphincter of Oddi Dysfunction) study randomized patients with post
      cholecystectomy pain, and little or no objective evidence for biliary
      obstruction, to sphincterotomy or sham intervention. Results at 1 year showed no
      benefit for the active treatment. We now report the outcomes at up to 5 years.
      METHODS: One hundred three patients completing 1 year, and still blinded to
      treatment allocation, were enrolled and followed by phone every 6 months for a
      median of 58 months (range, 17-71 months). Their success was assessed at the
      final visit by 2 criteria: (1) a low pain score (Recurrent Abdominal Pain and
      Disability instrument [RAPID] <6) and (2) much or very much improved on the
      Patients' Global Impression of Change (PGIC) questionnaire (both with no repeat
      intervention and not taking narcotics). RESULTS: By the RAPID criteria, success
      rates for the patients in the sphincterotomy and sham arms were similar: 26/65
      (40%) versus 16/38 (42%), respectively. However, by the PGIC criteria, actively
      treated patients fared worse: 16/43 (37%) versus 16/22 (73%). A total of 75
      patients underwent active treatment during the entire study. Their success rate
      by the RAPID criteria was 31 (41%) compared with 16 (62%) who had no active
      treatment at any time. CONCLUSIONS: These data confirm our initial report that
      endoscopic sphincterotomy is no better than sham intervention in these patients
      (and, by some criteria, worse), and that ERCP can no longer be recommended. The
      patients have genuine and often severe symptoms, and further research is needed
      to establish effective management. (Clinical trial registration number: 00688662
      05/3/2008.).

PMID- 28455163
TI  - Sex Differences in Outcomes After Discharge from the Emergency Department for
      Atrial Fibrillation/Flutter.
AB  - BACKGROUND: Atrial fibrillation and flutter (AFF) are the most common arrhythmias
      presenting to emergency departments (EDs). We examined sex differences in
      outcomes for patients with AFF discharged from the ED in Alberta, Canada.
      METHODS: ED presentations for AFF during 1999-2011 that ended in discharge were
      extracted from administrative databases for all Alberta residents (age >= 35
      years). Multivariable models determined the effect of sex on the time to ED
      return for AFF, the first follow-up visit with a physician, the first follow-up
      visit with a specialist (cardiologist or internal medicine physician), and death.
      RESULTS: There were 21,062 patients/ED presentations (47.5% women). About 10%
      returned to the ED for AFF after discharge; the time to return was similar for
      both sexes (P = 0.39). Time to a first physician visit was shorter (unadjusted
      hazard ratio [uHR] = 1.10) and time to a specialist follow-up visit was longer
      (uHR = 0.93) for women than for men. Interactions between sex and age,
      socioeconomic groups, and comorbidities were identified that changed the effect
      of sex on time to follow-up. More women died by 30 (1.3% vs 0.9%; P = 0.009) and
      90 (2.9% vs 2.4%, P = 0.02) days. The time between ED discharge and death was
      shorter for women in 1 socioeconomic group (P = 0.008) and for those with
      peripheral vascular disease (P = 0.02) or diabetes (P = 0.03). CONCLUSIONS: We
      identified sex differences for time to return to the ED, follow-up visit, and
      death (most importantly, increased mortality rates among women at 30 and 90
      days), and time to death remained significant after adjustment for other
      demographic and health-related variables. Our findings have important potential
      implications for physicians in the emergency setting.

PMID- 28455164
TI  - Microvascular complications and their associated risk factors in type 2 diabetes
      mellitus.
AB  - AIMS: The aim of this study was to determine the prevalence of microvascular
      complications and to identify the various risk factors related to these
      complications in subjects with diabetes. MATERIALS AND METHODS: The study was
      cross-sectional and conducted in Outdoor of BIRDEM, from July 2014 to December
      2014. Subjects were considered at age 30 to 60 years and duration of diabetes was
      2-10 years. Investigations included socio-demographic, anthropometry and blood
      pressure. Blood samples were collected for HbA1c, fasting plasma glucose (FBG), 2
      h after breakfast (2-hBG), total cholesterol (chol), triglyceride (TG), LDL, HDL,
      Hb% and serum creatinine. All the complications were taken from the medical
      record books which was diagnosed by physician. RESULTS: A total of 400 type 2
      diabetes mellitus patients were investigated in this study. The mean and SD of
      age was 50.05+/-7.54. The male and female subjects were 41.5% and 58.5%
      respectively. The prevalence of diabetic retinopathy, nephropathy, neuropathy was
      12.3%, 21.3% and 16.8% respectively. Logistic regression model estimated that
      increasing age (age>50y; OR=3.04; p=<0.001), female participants (OR=1.35;
      p=<0.04), rural patients (OR=3.75; p=<0.001), housewife (OR=1.89; p=<0.01) and
      retired patients (2.50; p=<0.03), lack of physical exercise, increasing HbA1c
      (p=<0.001), FBG (p=<0.001), 2-hBG (<0.001) and blood pressure (p=0.000) had
      independent significant risk factors for any of three microvascular
      complications. CONCLUSION: This study observed that about all the microvascular
      complications were developed from first three years after registration at BIRDEM.
      Increasing age, HbA1c, FBG, 2-hBG and blood pressure had significant risk factors
      for any type of microvascular complications.

PMID- 28455165
TI  - Angelica dahurica ameliorates the inflammation of gingival tissue via regulation
      of pro-inflammatory mediators in experimental model for periodontitis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Anti-inflammatory effects of Angelica dahurica
      (AD) have been reported in previous studies. In this study, we investigated the
      anti-inflammatory effects of AD on periodontitis. MATERIALS AND METHODS: Male
      Sprague-Dawley rats aged 7 weeks (n=7) were subjected to ligature around
      bilateral mandibular first molars. 1 and 100mg/mL of AD were topically applied to
      first molars for 14 days. Histological changes were observed in gingival
      epithelial layer, and the thickness of the gingival epithelial layer as well as
      the number of epithelial cells were quantified. To investigate the mRNA
      expression of pro-inflammatory cytokines in gingival tissues, reverse
      transcriptase polymerase chain reaction was performed. To confirm the anti
      inflammatory effects of AD, pro-inflammatory mediators including cytokines and NF
      kB, COX-2, and iNOS were analyzed in LPS-stimulated Raw 264.7 cells. RESULTS:
      Topical application of AD attenuated not only the thickness of epithelial layer,
      also the number of epithelial cells in gingival tissue. The expressions of IL
      1beta, IL-6, IL-8, and IFN-gamma in gingiva were significantly reduced by AD
      treatment. Additionally, the expressions of IL-1beta, IL-6, IL-8 and IFN-gamma
      mRNA were inhibited by AD in LPS-treated RAW264.7 macrophage cells. Furthermore,
      AD treatment decreased LPS-induced elevation of NF-kappaB, COX-2 and iNOS protein
      levels in RAW264.7 cells. CONCLUSION: Taken together, AD application ameliorated
      the hyperplasia of gingival epithelial layer by down-regulating pro-inflammatory
      mediators. AD might have therapeutic potentials for periodontal diseases.

PMID- 28455167
TI  - Protective and pathogenic memory plasma cells.
AB  - The immune system can be divided into two major parts: innate and adaptive
      immunity. Adaptive immunity is characterized by its major cellular players: the B
      and T cells. B cells will, in the context of an immune reaction, differentiate
      into plasma cells. These plasma cells produce antibodies, which are secreted.
      Antibodies are characterized by their specificity against a selected antigen and
      by their isotype. The isotype changes with the duration or phase of the immune
      reaction. Early immune reactions are usually characterized by the predominant
      production of IgM antibodies. With the persistence of the immune reaction
      immunoglobulin class switch occurs and plasma cells will produce IgG, IgE or IgA
      antibodies (Radbruch et al., 2006) [1].

PMID- 28455166
TI  - Biomechanical performance of a collagen meniscus implant with regard to suture
      material and irrigation fluid.
AB  - BACKGROUND: The role of meniscus scaffolds remains controversial as failure rates
      remain high. The aim of this study was to evaluate the pullout strength of
      different suture materials used for fixation of the Collagen Meniscus Implant
      (CMI) regarding different suture materials, and type or temperature of irrigation
      fluid. METHODS: One-hundred and twelve specimens were utilized with horizontal
      sutures and mounted to a dedicated test device. Loads were applied perpendicular
      to the CMI, until failure. Two differing suture materials - polydioxanone (PDS)
      and non-absorbable, braided polyester sutures (NABP) - were evaluated.
      Additionally, two common irrigation fluids - lactated Ringer's and electrolyte
      free, hypotonic Mannitol-Sorbitol solution - were evaluated. Specimens were
      further evaluated according to different temperatures of the irrigation fluid.
      Half of the constructs were tested at room temperature (20 degrees C) and half
      were evaluated at near-core body temperature (37 degrees C). RESULTS: PDS sutures
      showed a significantly higher load-to-failure compared to NABP sutures
      (P=0.0008). Regarding the type of irrigation fluid, the electrolyte-free Mannitol
      Sorbitol solution showed a significantly higher load-to-failure compared to the
      overall Ringer group (P b 0.0001). This was equivalent for both the PDS (P=0.015)
      and for the NABP sutures (P b 0.0001). The temperature of the irrigation fluid
      did not significantly influence load-to-failure. CONCLUSIONS: PDS sutures and
      electrolyte-free Mannitol-Sorbitol irrigation fluid provided the best
      biomechanical properties regarding load-to-failure testing. This study underlines
      the potential to improve construct stability for the CMI by alteration of the
      suture material and the type of irrigation fluid, which should be considered
      whenever scaffold fixation is conducted.

PMID- 28455168
TI  - ATRP-grown protein-polymer conjugates containing phenylpiperazine selectively
      enhance transepithelial protein transport.
AB  - Despite its patient-friendliness, the oral route is not yet a viable strategy for
      the delivery of biomacromolecular therapeutics. This is, in part, due to the
      large size of proteins, which greatly limits their absorption across the
      intestinal epithelium. Although chemical permeation enhancers can improve
      macromolecular transport, their positive impact is often accompanied by toxicity.
      One element potentially contributing to this toxicity is the lack of co
      localization of the enhancer with the protein drug, which can result in non
      specific permeation of the intestine as well as enhancer overdosing in some areas
      due to non-uniform distribution. To circumvent these issues, this study describes
      a new way of increasing protein permeability via a polymer conjugation process
      that co-localizes permeation enhancer with the protein. Based on previous reports
      demonstrating the utility of 1-phenylpiperazine as an intestinal permeation
      enhancer, we synthesized protein-polymer conjugates with a phenylpiperazine
      containing polymer using polymer-based protein engineering. A novel
      phenylpiperazine acrylamide monomer was synthesized and chain extended using atom
      transfer radical polymerization from the model protein bovine serum albumin
      (BSA). At non-cytotoxic doses, the protein-polymer conjugates induced a dose
      dependent reduction in the trans-epithelial electrical resistance of Caco-2
      monolayers and an impressive ~30-fold increase in BSA permeability. Furthermore,
      this permeability increase was selective, as the permeability of the small
      molecule calcein co-incubated with the protein-polymer conjugate increased only 5
      fold. Together, these data represent an important first step in the development
      of protein polymer conjugates that facilitate selective protein transport across
      membranes that are typically impermeable to macromolecules.

PMID- 28455170
TI  - Two-dose schedules for human papillomavirus vaccine: Systematic review and meta
      analysis.
AB  - Simpler schedules for human papillomavirus (HPV) vaccine delivery could improve
      vaccine coverage and the effectiveness of cervical cancer prevention. The
      objective of this study was to systematically review evidence about the effects
      of two-dose compared with three-dose schedules for human papillomavirus (HPV)
      vaccine and to describe the uptake of two-dose HPV vaccination schedules
      globally. We searched PubMed, the Cochrane Central Registry of Controlled Trials,
      trials registers, and manufacturers' databases from their earliest date to
      February 2016. We selected randomised controlled trials and controlled clinical
      trials that directly compared HPV vaccine schedules with two or three doses. We
      extracted data on immunological and clinical outcomes and used meta-analysis
      where appropriate. We also described the use of two-dose HPV vaccine schedules
      globally. We screened 1464 items and included seven eligible noninferiority
      trials in 11 countries. In randomised comparisons amongst adolescent girls (three
      trials), geometric mean concentrations (GMC) of antibodies against HPV16 and
      HPV18 were non-inferior or inconclusive, up to 24months after a two-dose compared
      with a three-dose schedule. One trial with a clinical outcome found no persistent
      HPV infections occurred after either two or three doses. In non-randomised
      comparisons, GMC were non-inferior or superior in adolescent girls receiving the
      two-dose schedule compared with women receiving the three-dose schedule for at
      least 21months after vaccination. By February 2017, 23 low and middle income and
      25 high income countries had adopted a two-dose HPV vaccination schedule. A two
      dose HPV vaccine schedule provides satisfactory immunological outcomes in
      adolescent girls, but uptake globally is limited, particularly in countries with
      the highest burden of cervical cancer.

PMID- 28455169
TI  - Economic impact of thermostable vaccines.
AB  - BACKGROUND: While our previous work has shown that replacing existing vaccines
      with thermostable vaccines can relieve bottlenecks in vaccine supply chains and
      thus increase vaccine availability, the question remains whether this benefit
      would outweigh the additional cost of thermostable formulations. METHODS: Using
      HERMES simulation models of the vaccine supply chains for the Republic of Benin,
      the state of Bihar (India), and Niger, we simulated replacing different existing
      vaccines with thermostable formulations and determined the resulting clinical and
      economic impact. Costs measured included the costs of vaccines, logistics, and
      disease outcomes averted. RESULTS: Replacing a particular vaccine with a
      thermostable version yielded cost savings in many cases even when charging a
      price premium (two or three times the current vaccine price). For example,
      replacing the current pentavalent vaccine with a thermostable version without
      increasing the vaccine price saved from $366 to $10,945 per 100 members of the
      vaccine's target population. Doubling the vaccine price still resulted in cost
      savings that ranged from $300 to $10,706, and tripling the vaccine price resulted
      in cost savings from $234 to $10,468. As another example, a thermostable
      rotavirus vaccine (RV) at its current (year) price saved between $131 and $1065.
      Doubling and tripling the thermostable rotavirus price resulted in cost savings
      ranging from $102 to $936 and $73 to $808, respectively. Switching to
      thermostable formulations was highly cost-effective or cost-effective in most
      scenarios explored. CONCLUSION: Medical cost and productivity savings could
      outweigh even significant price premiums charged for thermostable formulations of
      vaccines, providing support for their use.

PMID- 28455171
TI  - Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is
      associated with decreased immune responsiveness.
AB  - BACKGROUND: Indigenous adults residing in the Northern Territory of Australia
      experience elevated rates of invasive pneumococcal disease despite the routine
      use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised
      that the limited protection from 23vPPV may be due to hyporesponsiveness as a
      result of vaccine failure from repeated vaccination. To explore this possibility,
      we evaluated the immune response to a first and second dose of 23vPPV in
      Indigenous adults and a first dose of 23vPPV in non-Indigenous adults. METHODS:
      Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at
      baseline and at one month post-vaccination. Individuals were considered to have
      an adequate immune response if paired sera demonstrated either: a four-fold rise
      in antibody concentration; a two-fold rise if the post vaccination antibody was
      >1.3MUg/ml but <4.0MUg/ml; or a post-vaccination antibody concentration
      >4.0MUg/ml for at least half of the serotypes tested (12/23). Our per-protocol
      analysis included the comparison of outcomes for three groups: Indigenous adults
      receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous
      adults (N=25) receiving their first 23vPPV dose. RESULTS: All non-Indigenous
      adults receiving a first dose of 23vPPV mounted an adequate immune response
      (25/25). There was no significant difference in the proportion of individuals
      with an adequate response using our definition (primary endpoint), with 88% of
      Indigenous adults mounted an adequate response following first dose 23vPPV
      (53/60) compared to 70% having an adequate response following a second dose of
      23vPPV (14/20; p=0.05). The risk difference between Indigenous participants
      receiving first dose compared to non-Indigenous participants receiving first dose
      was significant when comparing a response threshold of at least 70% (-27%, 95%
      CI: -43% to -11%; p=0.01) and 90% (-38%, 95% CI: -60% to -16%; p=0.006) of
      serotypes with a positive response. CONCLUSION: Indigenous participants
      demonstrated a poorer response to a first dose 23vPPV compared to their non
      Indigenous counterparts, with lower IgG following a second 23vPPV dose. These
      findings highlight the critical need to evaluate the efficacy of future
      pneumococcal vaccine programs in the Australian Indigenous populations that
      recommend repeated doses of 23vPPV.

PMID- 28455172
TI  - Inactivated polio vaccines from three different manufacturers have equivalent
      safety and immunogenicity when given as 1 or 2 additional doses after bivalent
      OPV: Results from a randomized controlled trial in Latin America.
AB  - BACKGROUND: Since April 2016 inactivated poliovirus vaccine (IPV) has been the
      only routine source of polio type 2 protection worldwide. With IPV supply
      constraints, data on comparability of immunogenicity and safety will be important
      to optimally utilize available supplies from different manufacturers. METHODS: In
      this multicenter phase IV study, 900 Latin American infants randomly assigned to
      six study groups received three doses of bOPV at 6, 10 and 14weeks and either one
      IPV dose at 14weeks (groups SP-1, GSK-1 and BBio-1) or two IPV doses at 14 and
      36weeks (groups SP-2, GSK-2 and BBio-2) from three different manufacturers.
      Children were challenged with mOPV2 at either 18 (one IPV dose) or 40weeks (two
      IPV doses) and stools were collected weekly for 4weeks to assess viral shedding.
      Serum neutralizing antibodies were measured at various time points pre and post
      vaccination. Serious adverse events and important medical events (SAE and IME)
      were monitored for 6months after last study vaccine. RESULTS: At week 18, 4weeks
      after one dose of IPV, overall type 2 seroconversion rates were 80.4%, 80.4% and
      73.3% for SP-1, GSK-1 and BBio-1 groups, respectively; and 92.6%, 96.8% and 88.0%
      in those who were seronegative before IPV administration. At 40weeks, 4weeks
      after a second IPV dose, type 2 seroconversion rates were >=99% for any of the
      three manufacturers. There were no significant differences in fecal shedding
      index endpoint (SIE) after one or two IPV doses (SP: 2.3 [95% CI: 2.1-2.6]); GSK:
      2.2 [1.7-2.5]; BBio 1.8 [1.5-2.3]. All vaccines appeared safe, with no vaccine
      related SAE or IME. CONCLUSION: Current WHO prequalified IPV vaccines are safe
      and induce similar humoral and intestinal immunity after one or two doses. The
      parent study was registered with ClinicalTrials.gov, number NCT01831050.

PMID- 28455173
TI  - The impacts of email reminder/recall on adolescent influenza vaccination.
AB  - BACKGROUND: We sought to: (1) explore the feasibility of using email for seasonal
      influenza vaccination reminders to parents of adolescents and (2) assess
      influenza vaccination rates among adolescents whose parents were randomized to
      either receive or not receive email reminders. METHODS: Email addresses were
      obtained for parents of patients 10-18years from 4 practices in Michigan.
      Addresses were randomized to either receive email reminders, or not. Reminder
      messages were sent during October 2012-March 2013 (Season 1) and October 2013
      March 2014 (Season 2). Vaccination status was determined 60days following the
      last email reminder for each season using the statewide Michigan Care Improvement
      Registry (MCIR); per protocol bivariate and multivariate logistic regression
      analyses were conducted to evaluate reminder notification. RESULTS: After email
      cleaning, testing, and matching with MCIR, approximately half of email addresses
      (2348 of 5312 in Season 1; 3457 of 6549 in Season 2) were randomized. Bivariate
      analyses found that influenza vaccination within 60days after notification date
      was similar among those notified (34%) versus not notified (29%) in both Season 1
      (p=0.06) and Season 2 (39% vs. 37%, p=0.20). However, multivariate models
      adjusted for season, site, and receipt of notification in two seasons found a
      higher likelihood of influenza vaccination among children that received
      notification (aOR=1.28, 95% CI=1.09, 1.51); in addition, differences in influenza
      vaccination were also observed between practice sites (range: p=0.15 to p<0.001).
      CONCLUSIONS: We found that practice-based email influenza vaccine reminders to
      parents of adolescents are feasible, but not without complications. Our study
      demonstrates that email reminders from practices can yield increases in influenza
      vaccination rates among adolescents. Practices should consider email as an option
      for influenza reminders and establish business practices for collecting and
      maintaining patient email addresses. This study is registered at
      www.ClinicalTrials.gov id #NCT01732315.

PMID- 28455174
TI  - Improving adult immunization equity: Where do the published research literature
      and existing resources lead?
AB  - Evidence suggests that disparities in adult immunization (AI) rates are growing.
      Providers need adequate patient resources and information about successful
      interventions to help them engage in effective practices to reduce AI
      disparities. The primary purposes of this paper were to review and summarize the
      evidence base regarding interventions to reduce AI disparities and to scan for
      relevant resources that could support providers in their AI efforts to
      specifically target disparities. First, building on a literature review conducted
      by the U.S. Centers for Disease Control and Prevention, we searched the peer
      reviewed literature to identify articles that either discussed interventions to
      reduce AI disparities or provided reasons and associations for disparities. We
      scanned the articles and conducted an internet search to identify tools and
      resources to support efforts to improve AI rates. We limited both searches to
      resources that addressed influenza, pneumococcal, hepatitis B, Tdap, and/or
      herpes zoster vaccinations. We found that most articles characterized AI
      disparities, but several discussed strategies for reducing AI disparities,
      including practice-based changes, communication and health literacy approaches,
      and partnering with community-based organizations. The resources we identified
      were largely fact sheets and handouts for patients and journal articles for
      providers. Most resources pertain to influenza vaccination and Spanish was the
      most prevalent language after English. More evaluation is needed to assess the
      health literacy levels of the materials. We conclude that additional research is
      needed to identify effective ways to reduce AI disparities and more resources are
      needed to support providers in their efforts. We recommend identifying best
      practices of high performers, further reviewing the appropriateness and
      usefulness of available resources, and prioritizing which gaps should be
      addressed.

PMID- 28455175
TI  - Morbid Obesity in Total Knee Arthroplasty: Joint-Specific Variance in Outcomes
      for Operative Time, Length of Stay, and Readmission.
AB  - BACKGROUND: It is increasingly apparent that the effect of obesity in
      arthroplasty is joint-specific. This study evaluates the effects of morbid
      obesity on primary total knee arthroplasty by comparing short-term outcomes
      between a morbidly obese (body mass index >=40 kg/m2) and a normal weight (body
      mass index 18.5-<25 kg/m2) cohort at our institution between January 2003 and
      December 2010. METHODS: One hundred seventeen morbidly obese patients were
      compared with 94 normal weight patients. Operative time, length of stay,
      complications, 30-day readmission, and readmission length were compared. RESULTS:
      Morbid obesity conveyed no significant increase in 30-day readmission. Operative
      time was increased at 100 minutes in the morbidly obese group, compared with 90.5
      minutes (P = .026). CONCLUSION: Morbid obesity conveyed no increased risk of
      length of stay or readmission in this cohort.

PMID- 28455176
TI  - Prolonged Conservative Management in Total Joint Arthroplasty: Harming the
      Patient?
AB  - BACKGROUND: It is important to understand the long-term consequences of
      postponing total joint arthroplasty until the onset of severe functional
      impairment. Therefore, the purpose of this investigation was to determine and
      compare the midterm to long-term postoperative outcomes of patients who underwent
      total joint arthroplasty with severe vs less severe preoperative functional
      impairment. METHODS: A total of 105 primary unilateral total hip/knee
      arthroplasty patients were studied. Patients were divided into 2 groups-severely
      functionally impaired (preoperative Western Ontario and McMaster Osteoarthritis
      Index function >=51 points) and functionally impaired (preoperative Western
      Ontario and McMaster Osteoarthritis Index function <51 points). RESULTS: At an
      average of 11.2 years postoperatively, the patients who were severely
      functionally impaired preoperatively had worse outcomes than did the patients
      with less severe preoperative functional impairment. CONCLUSION: Our data suggest
      that, after surgery, it is unlikely that patients who are severely functionally
      impaired preoperatively will ever catch up to patients who have the surgery with
      less severe functional impairment.

PMID- 28455177
TI  - Temporal Relations of Unplanned Readmissions Following Total Knee Arthroplasty: A
      Study of Large State Inpatient Databases.
AB  - BACKGROUND: Centers for Medicare & Medicaid Services stipulate a 90-day global
      period for hospitals for unplanned readmissions after primary total knee
      arthroplasty (TKA). However, not all readmissions are directly attributable to
      index surgery, and reasons for readmissions vary during this time period. This
      study identifies causes and temporal relations of readmissions using large state
      inpatient databases. METHODS: State inpatient databases of New York and
      California were queried for all primary TKAs performed from 2005 to 2011 and
      frequencies of all causes of unplanned readmission were identified from 0 to 90
      days after index surgery using the International Classification of Diseases,
      Ninth Revision, codes. Temporal differences in proportions of readmission
      diagnoses were tested using the Pearson chi-square test. RESULTS: The query
      identified 419,805 cases of primary TKA from 2005 to 2011. There were 26,924
      readmissions during the 90-day recovery period, with 15,547 (57.7%) at 0-30 days,
      6593 (24.5%) at 31-60 days, and 4784 (17.8%) at 61-90 days. Primary diagnoses at
      readmission that were identified to be directly attributable to surgery comprised
      38.3% readmissions at 0-30 days, 24.0% at 31-60 days, and 16.3% at 60-90 days.
      Proportion of readmissions directly attributable to surgery decreased over the 90
      day period after index surgery. CONCLUSION: From this analysis of 2 large state
      inpatient databases, primary diagnoses at readmission vary with time, and
      majority of these may not be directly attributable to index surgery or
      postoperative state up to 90 days. These findings suggest that the current 90-day
      global period policy for this procedure should be reformed to better reflect the
      profile of unplanned readmissions after TKA.

PMID- 28455178
TI  - The Patient Experience: An Analysis of Orthopedic Surgeon Quality on Physician
      Rating Sites.
AB  - BACKGROUND: With the advent of the Consensus Core of Orthopedic Measures,
      arthroplasty surgeons are increasingly subjected to public performance reviews on
      physician-rating sites. Therefore, we evaluated (1) web site details of physician
      rating sites, (2) differences between sites and the Consensus Core, (3) published
      patient experiences, (4) search rank among sites, and (5) differences between
      academic vs nonacademic and arthroplasty vs nonarthroplasty surgeons. METHODS:
      The 5 busiest physician-rating sites were analyzed. To compare physician-rating
      sites to the Consensus Core, 3 reviewers analyzed the web site details. To
      evaluate patient ratings and reviews, orthopedists from the top 5 academic and
      nonacademic hospitals (2016 US News & World Report) were analyzed. Institution
      produced rating sites were also analyzed. Findings were stratified between
      academic vs nonacademic and arthroplasty vs nonarthroplasty surgeons. Five
      hundred and six staff surgeons across 10 academic and nonacademic affiliated
      hospitals yielded 27,792 patient-generated ratings and reviews for 1404 accounts.
      RESULTS: Features on all sites were practice location, languages spoken, and
      patient experience. Two sites autogenerated profiles of surgeons without consent.
      No physician-rating site contained all Consensus Core domains. The composite
      orthopedic surgeon rating was 4.1 of 5. No significant differences were found
      between academic and nonacademic affiliated surgeons. Arthroplasty surgeons had a
      greater number of reviews and ratings on 2 sites. CONCLUSION: Reliability of
      physician-rating sites is questionable, as none contained all Consensus Core
      domains. Autogeneration of surgeon profiles is occurring, and no differences
      between academic vs nonacademic or arthroplasty vs nonarthroplasty surgeons were
      found. Institution-produced sites may serve to better promote and market
      surgeons.

PMID- 28455179
TI  - Nonelective Primary Total Hip Arthroplasty: The Effect of Discharge Destination
      on Postdischarge Outcomes.
AB  - BACKGROUND: Medicare has enacted a mandatory bundled payment program for primary
      total joint arthroplasty that includes nonelective primary total hip arthroplasty
      (THA). Efficient postacute care management has been identified as an opportunity
      to improve value for patients. We aimed to identify risk factors for and compare
      rates of complications by discharge destination and then use those factors to
      risk-stratify non-elective THA patients. METHODS: Patients who underwent
      nonelective primary THA from 2011 to 2014 were identified in the American College
      of Surgeons National Surgical Quality Improvement Program database and
      categorized into those discharged to skilled nursing facility or inpatient
      rehabilitation facility vs home self-managed/home health (HHH). Bivariate and
      multivariate analyses of risk factors for postdischarge adverse events were
      performed using patient characteristics and intraoperative variables. RESULTS: In
      bivariate analysis, skilled nursing facility or inpatient rehabilitation facility
      patients compared with HHH patients, had lower rates of postdischarge severe
      adverse events (SAEs; 49% vs 58%; P < .001) and unplanned 30-day readmissions
      (71% vs 83%; P < .001). HHH discharged patients with 1 or more of risk factors
      had a 1.85-6.18 times odds of complications within the first 14 days. CONCLUSION:
      The most important risk factors for predicting postdischarge SAE and readmission
      are predischarge SAE, dependent functional status, body mass index >40 kg/m2,
      smoking, diabetes, chronic steroid use, and American Society of Anesthesiologists
      class 3/4. Nonelective THA patients without these risk factors may be safely
      discharged to home after THA. Orthopedic surgeons and their nonelective THA
      patients must agree on the most appropriate discharge destination through a
      shared decision-making process that takes into account these significant risk
      factors and other psychosocial factors.

PMID- 28455180
TI  - The Cost of Unnecessary Hospital Days for Medicare Joint Arthroplasty Patients
      Discharging to Skilled Nursing Facilities.
AB  - BACKGROUND: The 72-hour Medicare mandate (3-night stay rule) requires a 3-day
      inpatient stay for patients discharging to skilled nursing facilities (SNFs).
      Studies show that 48%-64% of Medicare total joint arthroplasty (TJA) patients are
      safe for discharge to SNFs on postoperative day (POD) #2. The purpose of this
      study was to extrapolate the financial impact of the 3-night stay rule. METHODS:
      The American College of Surgeons National Surgical Quality Improvement Program
      database was queried for all primary TJAs performed in 2015. Discharge
      destination was recorded. Institutional cost accounting examined costs for
      patients discharging on POD #2 vs POD #3. RESULTS: A total of 42,423 TJAs (14,395
      total hip arthroplasties [THAs] and 28,028 total knee arthroplasties [TKAs]) were
      performed in patients over the age of 65 years. Of these patients, 5252 THAs
      (36.5%) and 12,022 TKAs (42.9%) were discharged from the hospital on POD #3, with
      2404 THAs (16.7%) and 5083 TKAs (18.1%) being discharged to SNFs. Institutional
      cost accounting revealed hospital costs for THA were $2014 more, whereas hospital
      costs for TKA were $1814 more for a 3-day length of stay when compared with a 2
      day length of stay (P < .001). The mean charge per day for an SNF was $486.
      CONCLUSION: The National Surgical Quality Improvement Program database is a
      representative sample of all surgeries performed in the United States.
      Extrapolating our findings to all Medicare TJAs nationally gives an estimated $63
      million in annual savings. Medicare mandated, but potentially medically
      unnecessary inpatient days at a higher level of care increase the total cost for
      TJAs. Policies regarding minimum stay requirements before discharge should be re
      evaluated.

PMID- 28455181
TI  - Discharge to Inpatient Facilities After Total Hip Arthroplasty Is Associated With
      Increased Postdischarge Morbidity.
AB  - BACKGROUND: Discharge disposition accounts for significant variability in costs
      after elective total hip arthroplasty (THA). Therefore, institutions must
      evaluate the short-term clinical outcomes associated with postdischarge care
      options. The present study intends to characterize the associations between short
      term morbidity after primary THA and discharge destination. METHODS: Primary
      elective unilateral THA cases performed for osteoarthritis were identified in the
      American College of Surgeons National Surgical Quality Improvement Program
      registry from 2011 to 2014. Propensity scores were used to adjust for selection
      bias in discharge destination, based on demographics, obesity class, preoperative
      functional status, modified Charlson comorbidity index, American Society of
      Anesthesiologists (ASA) class, and the presence of predischarge complications.
      Propensity-adjusted multivariate logistic regressions were used to examine
      associations between discharge destination and postdischarge complications,
      controlling for selection bias based on observable patient characteristics.
      RESULTS: Among 54,837 THA cases included in the study, 40,576 (74%) were
      discharged home, and 14,261 (26%) were discharged to inpatient facilities. In
      multivariate propensity-adjusted analyses, patients discharged to continued
      inpatient care after THA were more likely to have septic complications (odds
      ratio, 2.34; 95% confidence interval, 1.58-3.45), urinary complications (1.51;
      1.21-1.90), readmission (1.44; 1.29-1.59), wound complications (1.31; 1.09-1.57),
      and respiratory complications (1.93; 1.21-3.07). CONCLUSION: Discharge to
      continued inpatient care following THA is associated with increased odds of
      postdischarge morbidity and unplanned readmission, after propensity score
      adjustment for predischarge characteristics. Additional research is needed on the
      impact of devoting resources toward facilitating discharge to home after THA.

PMID- 28455182
TI  - Comparison of 3 Routes of Administration of Tranexamic Acid on Primary Unilateral
      Total Knee Arthroplasty: A Prospective, Randomized, Controlled Study.
AB  - BACKGROUND: The mode of administration for tranexamic acid (TXA) to significantly
      reduce the decrease in hemoglobin (Hb), number of transfusions, relevant costs,
      and side effects in patients undergoing primary unilateral total knee
      arthroplasty (TKA) has not been resolved. METHODS: A total of 560 patients
      undergoing primary unilateral TKA were randomized into 4 groups: intravenous
      group (140 patients receiving 2 doses of 20 mg/kg intravenous TXA), topical group
      (140 patients administered 3.0 g topical TXA), oral group (140 patients given 2
      doses of 20 mg/kg oral TXA), and a control group (140 patients not given TXA).
      The primary outcomes included postoperative 48-hour Hb loss and drainage volume,
      number of transfusions, transfusion and TXA costs, and thromboembolic
      complications. Secondary outcomes were postoperative inpatient time and wound
      healing 3 weeks after TKA. RESULTS: Baseline data among the 4 groups were
      similar. The 48-hour Hb loss and drainage volume in the intravenous, topical, and
      oral groups were significantly less (P < .05) than those in the control group,
      and the latter had significantly more transfusions and transfusion costs than the
      other 3 groups (P < .05). The TXA cost was lowest in the oral group compared with
      that in the topical and intravenous groups (P < .05). No differences in
      thromboembolic complications, postoperative inpatient time, or wound healing were
      observed among the groups. However, wound dehiscence and continuous wound
      discharge occurred in the topical group. CONCLUSION: All the 3 modes of TXA
      administration significantly reduced postoperative Hb loss, the number of
      transfusions, and transfusion costs compared with those in the control group. No
      pulmonary embolism or infection was observed. Oral TXA is recommended because it
      provided a similar clinical benefit and resulted in the lowest TXA cost compared
      with the other 2 modes of TXA administration.

PMID- 28455183
TI  - The effects of competition and implicit power motive on men's testosterone,
      emotion recognition, and aggression.
AB  - A contribution to a special issue on Hormones and Human Competition. We
      investigated the effects of competition on men's testosterone levels and assessed
      whether androgen reactivity was associated with subsequent emotion recognition
      and reactive and proactive aggression. We also explored whether personalized
      power (p Power) moderated these relationships. In Study 1, 84 males competed on a
      number tracing task and interpreted emotions from facial expressions. In Study 2,
      72 males competed on the same task and were assessed on proactive and reactive
      aggression. In both studies, contrary to the biosocial model of status (Mazur,
      1985), winners' testosterone levels decreased significantly while losers' levels
      increased, albeit not significantly. Personalized power moderated the effect of
      competition outcome on testosterone change in both studies. Using the aggregate
      sample, we found that the effect of decreased testosterone levels among winners
      (compared to losers) was significant for individuals low in p Power but not for
      those with medium or high p Power. Testosterone change was positively related to
      emotion recognition, but unrelated to either aggression subtype. The testosterone
      mediated relationship between winning and losing and emotion recognition was
      moderated by p Power. In addition, p Power moderated the direct (i.e., non
      testosterone mediated) path between competition outcome and emotion recognition
      and both types of aggression: high p-Power winners were more accurate at
      deciphering others' emotions than high p-Power losers. Finally, among high p
      Power men, winners aggressed more proactively than losers, whereas losers
      aggressed more reactively than winners. Collectively, these studies highlight the
      importance of implicit power motivation in modulating hormonal, cognitive, and
      behavioral outcomes arising from human competition.

PMID- 28455184
TI  - Arabidopsis glucosinolates trigger a contrasting transcriptomic response in a
      generalist and a specialist herbivore.
AB  - Phytophagous insects have to deal with toxic defense compounds from their host
      plants. Although it is known that insects have evolved genes and mechanisms to
      detoxify plant allochemicals, how specialist and generalist precisely respond to
      specific secondary metabolites at the molecular level is less understood. Here we
      studied the larval performance and transcriptome of the generalist moth Heliothis
      virescens and the specialist butterfly Pieris brassicae feeding on Arabidopsis
      thaliana genotypes with different glucosinolate (GS) levels. H. virescens larvae
      gained significantly more weight on the GS-deficient mutant quadGS compared to
      wild-type (Col-0) plants. On the contrary, P. brassicae was unaffected by the
      presence of GS and performed equally well on both genotypes. Strikingly, there
      was a considerable differential gene expression in H. virescens larvae feeding on
      Col-0 compared to quadGS. In contrast, compared to H. virescens, P. brassicae
      displayed a much-reduced transcriptional activation when fed on both plant
      genotypes. Transcripts coding for putative detoxification enzymes were
      significantly upregulated in H. virescens, along with digestive enzymes and
      transposable elements. These data provide an unprecedented view on
      transcriptional changes that are specifically activated by GS and illustrate
      differential molecular responses that are linked to adaptation to diet in
      lepidopteran herbivores.

PMID- 28455185
TI  - Gaps exist in the current guidance on the use of randomized controlled trial
      study protocols in systematic reviews.
AB  - OBJECTIVES: The use of trial registry records and randomized controlled trial
      (RCT) study protocols can assist systematic reviewers in evaluating and,
      possibly, minimizing publication and selective reporting biases. This study
      examined current guidance on the use of registry records and RCT study protocols
      from key systematic review organizations, institutes, and collaborations. STUDY
      DESIGN AND SETTING: Handbooks, guidelines, and standard documents from key
      systematic review organizations and the EQUATOR network database were identified.
      Textual excerpts providing guidance on the use of trial registry records, RCT
      protocols, and ongoing/unpublished studies were extracted independently by two
      reviewers and coded into a systematic review framework. RESULTS: Eleven documents
      published in English between 2009 and 2016 were included. Guidance for using RCT
      protocols and trial registry records was provided for 7 of 16 framework
      categories, and guidance for using unpublished and ongoing studies was available
      for 8 of 16 categories. CONCLUSION: This study identified gaps and ambiguities in
      language in guidance on the use of RCT protocols and trial registry records. To
      encourage and assist reviewers to use trial registry records and RCT study
      protocols in systematic reviews, current guidance should be expanded and
      clarified.

PMID- 28455186
TI  - Further evidence supporting the need for improved risk stratification of thin
      melanoma.

PMID- 28455188
TI  - Near-infrared light-activatable polymeric nanoformulations for combined therapy
      and imaging of cancer.
AB  - Near infrared (NIR) light allows deep tissue penetration and high spatial
      resolution due to the reduced scattering of long-wavelength photons. NIR light
      activatable polymer nanoparticles are widely exploited for enhanced cancer
      imaging (diagnosis) and therapy owing to their superior photostability,
      photothermal conversion efficiency (or high emission rate), and minimal toxicity
      to cells and tissues. This review surveys the most recent advances in the
      synthesis of different NIR-absorbing and emissive polymer nanoformulations, and
      their applications for cancer imaging, photothermal therapy, theranostics and
      combination therapy by delivering multiple small molecule chemotherapeutics.
      Photo-responsive drug delivery systems for NIR light-triggered drug release are
      also discussed with particular emphasis on their molecular designs and
      formulations as well as photo-reaction mechanisms. Finally, outlook and
      challenges are presented regarding potential clinical applications of NIR light
      activatable nanoformulations.

PMID- 28455187
TI  - Progress and opportunities for enhancing the delivery and efficacy of checkpoint
      inhibitors for cancer immunotherapy.
AB  - Despite the advent of immune checkpoint blockade for effective treatment of
      advanced malignancies, only a minority of patients responds to therapy and
      significant immune-related adverse events remain to be minimized. Innovations in
      engineered drug delivery systems and controlled release strategies can improve
      drug accumulation at and retention within target cells and tissues in order to
      enhance therapeutic efficacy while simultaneously reducing drug exposure in off
      target tissues to minimize the potential for treatment-associated toxicities.
      This review will outline basic principles of the immune physiology of checkpoint
      signaling, the existing knowledge of dose-efficacy relationships in checkpoint
      inhibition, the influence of administration route on treatment efficacy, as well
      as the resulting checkpoint inhibitor antibody biodistribution profiles amongst
      target versus systemic tissues. It will also highlight recent successes in the
      application of drug delivery principles and technologies towards augmenting
      checkpoint blockade therapy in cancer. Delivery strategies that have been
      developed for other therapeutic and immunotherapy applications with as-of-yet
      underexplored potential in checkpoint inhibition therapy will also be discussed.

PMID- 28455190
TI  - Association of Traumatic Brain Injury With Chronic Pain in Iraq and Afghanistan
      Veterans: Effect of Comorbid Mental Health Conditions.
AB  - OBJECTIVE: To characterize the association between traumatic brain injury (TBI)
      and chronic pain and pain disability in the context of comorbid conditions,
      posttraumatic stress disorder (PTSD), and depression to better inform care of
      combat veterans. DESIGN: Retrospective cohort study. SETTING: Medical centers and
      community clinics. PARTICIPANTS: Combat veterans (N=116,913) who received
      Veterans Affairs care between October 1, 2007 and March 31, 2015, completed a
      Comprehensive Traumatic Brain Injury Evaluation, and received a criterion
      standard diagnosis of TBI (none, mild, or moderate to severe). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Chronic pain defined as >=2 of the same pain
      diagnoses >=90 days apart and pain disability defined as self-reported pain
      causing moderate to very severe interference with daily functioning. RESULTS:
      Fifty-seven percent received >=1 chronic pain diagnosis. Compared to those with
      no TBI, PTSD, or depression, there was an independent risk for chronic pain in
      veterans with mild TBI, which was higher in veterans with moderate to severe TBI.
      The risk of chronic pain was additive and highest when all 3 conditions-TBI,
      depression, and PTSD-were copresent (adjusted relative risk, 1.53 and 1.62 [95%
      confidence interval, 1.50-1.66] for mild and moderate or severe TBI,
      respectively, plus other diagnoses). The relation of pain disability to TBI,
      PTSD, and depression followed a similar additive pattern. CONCLUSIONS: In combat
      veterans, chronic pain and pain disability are most commonly associated with TBI
      in conjunction with PTSD, depression, or both. Integrated models of care that
      simultaneously address pain in conjunction with TBI, PTSD, and depression will
      likely be the most clinically effective.

PMID- 28455191
TI  - Electroacupuncture for Poststroke Spasticity: A Systematic Review and Meta
      Analysis.
AB  - OBJECTIVE: To evaluate the effects and safety of electroacupuncture (EA) for
      stroke patients with spasticity. DATA SOURCES: Five English databases (PubMed,
      EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Allied and
      Complementary Medicine Database) and 4 Chinese databases (Chinese Biomedical
      Database, Chinese National Knowledge Infrastructure, Chongqing VIP Database,
      Wanfang Database) were searched from their inception to September 2016. STUDY
      SELECTION: Randomized controlled trials were included if they measured spasticity
      with the Modified Ashworth Scale (MAS) in stroke patients and investigated the
      add-on effects of electroacupuncture to routine pharmacotherapy and
      rehabilitation therapies. DATA EXTRACTION: Information on patients, study design,
      treatment details and outcomes assessing spasticity severity, motor function, and
      activities of daily living was extracted. DATA SYNTHESIS: In total, 22 trials
      involving 1425 participants met the search criteria and were included. The
      estimated add-on effects of EA to reduce spasticity in the upper limbs as
      measured by the MAS (standardized mean difference [SMD]=-.57; 95% confidence
      interval [CI], -.84 to -.29), and to improve overall motor function as measured
      by the Fugl-Meyer Assessment of Sensorimotor Recovery (mean difference
      [MD]=10.60; 95% CI, 8.67-12.53) were significant. Significant add-on effects of
      EA were also shown for spasticity in the lower limbs, lower-limb motor function,
      and activities of daily living ([SMD=-.88; 95% CI, -1.42 to -.35;], [MD=4.42; 95%
      CI, .06-8.78], and [MD=6.85; 95% CI, 3.64-10.05], respectively), although with
      high heterogeneity. For upper-limb motor function, no significant add-on effects
      of EA were found. CONCLUSIONS: EA combined with conventional routine care has the
      potential of reducing spasticity in the upper and lower limbs and improving
      overall and lower extremity motor function and activities of daily living for
      patients with spasticity, within 180 days poststroke. Further studies of high
      methodological and reporting quality are needed to confirm the effects and safety
      of EA, and to explore the adequate and optimal protocol of EA for poststroke
      spasticity, incorporating a group of comprehensive outcome measures in different
      populations.

PMID- 28455189
TI  - Biomaterial strategies for generating therapeutic immune responses.
AB  - Biomaterials employed to raise therapeutic immune responses have become a complex
      and active field. Historically, vaccines have been developed primarily to fight
      infectious diseases, but recent years have seen the development of
      immunologically active biomaterials towards an expanding list of non-infectious
      diseases and conditions including inflammation, autoimmunity, wounds, cancer, and
      others. This review structures its discussion of these approaches around a
      progression from single-target strategies to those that engage increasingly
      complex and multifactorial immune responses. First, the targeting of specific
      individual cytokines is discussed, both in terms of delivering the cytokines or
      blocking agents, and in terms of active immunotherapies that raise neutralizing
      immune responses against such single cytokine targets. Next, non-biological
      complex drugs such as randomized polyamino acid copolymers are discussed in terms
      of their ability to raise multiple different therapeutic immune responses,
      particularly in the context of autoimmunity. Last, biologically derived matrices
      and materials are discussed in terms of their ability to raise complex immune
      responses in the context of tissue repair. Collectively, these examples reflect
      the tremendous diversity of existing approaches and the breadth of opportunities
      that remain for generating therapeutic immune responses using biomaterials.

PMID- 28455192
TI  - Associations Between Resilience, Community Belonging, and Social Participation
      Among Community-Dwelling Older Adults: Results From the Eastern Townships
      Population Health Survey.
AB  - OBJECTIVE: To examine the associations between resilience, community belonging,
      and social participation, and the moderating effect of resilience on the
      association between community belonging and social participation among community
      dwelling older adults. DESIGN: Cross-sectional; secondary analyses of the Eastern
      Townships Population Health Survey. SETTING: Community. PARTICIPANTS: A sample
      (N=4541) of women (n=2485) and men (n=2056) aged >=60 years was randomly selected
      according to area. Most participants had <14 years of schooling, owned their
      dwelling, were retired, had 1 or 2 chronic conditions, and did not have
      depressive symptoms. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self
      reported data on age, education, depressive symptoms, social participation,
      community belonging, and resilience were collected by phone interviewer
      administered questionnaire. A social participation scale measured frequency of
      participation in 8 community activities. A 4-point Likert scale ranging from
      "very strong" to "very weak" estimated sense of belonging to the local community.
      Social participation and sense of belonging questions came from Statistics Canada
      surveys. Resilience was assessed with the 10-item Connor-Davidson Resilience
      Scale, capturing the ability to cope with adversity. RESULTS: Controlling for
      age, education, and psychological distress, greater resilience and community
      belonging were associated with greater social participation among women (R2=.13;
      P<.001) and men (R2=.09; P<.001). The association between community belonging and
      social participation varied as a function of resilience, especially in men.
      Greater community belonging further enhanced social participation, especially
      among women (P=.03) and men (P<.01) with greater resilience (moderator effect).
      CONCLUSIONS: Resilience moderates the association between community belonging and
      social participation among community-dwelling older women and, especially, men.
      Interventions targeting social participation should consider the potential impact
      of resilience on improving community belonging. Future studies should investigate
      why resilience moderates associations between community belonging and social
      participation, and how to enhance resilience among older adults.

PMID- 28455193
TI  - Associations Between Self-Efficacy and Secondary Health Conditions in People
      Living With Spinal Cord Injury: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To describe the association between self-efficacy and secondary health
      conditions (SHCs) in people living with spinal cord injury (SCI). DATA SOURCES:
      PubMed, EMBASE, the Cochrane Library, and CINAHL were systematically searched
      from database inception to September 2016. STUDY SELECTION: Studies describing
      patients living with SCI in which self-efficacy was measured by a standardized
      questionnaire and an association was made with somatic or psychological SHCs.
      DATA EXTRACTION: An independent extraction by multiple observers was performed
      based on the Strengthening the Reporting of Observational Studies in Epidemiology
      statements checklist. A meta-analysis concerning the association between self
      efficacy and SHCs in people with SCI was performed if a minimum of 4 comparable
      studies were available. DATA SYNTHESIS: Of 670 unique articles screened, 22 met
      the inclusion criteria. Seven of these 22 studies investigated associations
      between self-efficacy and somatic SHCs. Only a trend toward an association
      between higher self-efficacy and less pain, fatigue, number of SHCs, and
      limitations caused by SHCs was found. Twenty-one studies described the
      association between self-efficacy and psychological SHCs. All correlations of
      higher self-efficacy with fewer depressive (18 studies) and anxiety symptoms (7
      studies) were significant, and meta-analysis showed a strong negative correlation
      of -.536 (-.584 to -.484) and -.493 (-.577 to -.399), respectively. A small
      number of studies (2) showed a trend toward a positive correlation between self
      efficacy and quality of life. CONCLUSIONS: Self-efficacy is negatively associated
      with depressive and anxiety symptoms in SCI. Therefore, self-efficacy seems an
      important target in the rehabilitation of patients living with SCI. More research
      is necessary to clarify the associations between self-efficacy and somatic SHCs.
      Future research should also focus on different types of self-efficacy and their
      association with SHCs.

PMID- 28455194
TI  - Improving medication information transfer between hospitals, skilled-nursing
      facilities, and long-term-care pharmacies for hospital discharge transitions of
      care: A targeted needs assessment using the Intervention Mapping framework.
AB  - INTRODUCTION: Patients transitioning from the hospital to a skilled nursing home
      (SNF) are susceptible to medication-related errors resulting from fragmented
      communication between facilities. Through continuous process improvement efforts
      at the hospital, a targeted needs assessment was performed to understand the
      extent of medication-related issues when patients transition from the hospital
      into a SNF, and the gaps between the hospital's discharge process, and the needs
      of the SNF and long-term care (LTC) pharmacy. We report on the development of a
      logic model that will be used to explore methods for minimizing patient care
      medication delays and errors while further improving handoff communication to SNF
      and LTC pharmacy staff. METHODS: Applying the Intervention Mapping (IM)
      framework, a targeted needs assessment was performed using quantitative and
      qualitative methods. Using the hospital discharge medication list as reference,
      medication discrepancies in the SNF and LTC pharmacy lists were identified. SNF
      and LTC pharmacy staffs were also interviewed regarding the continuity of
      medication information post-discharge from the hospital. RESULTS: At least one
      medication discrepancy was discovered in 77.6% (n = 45/58) of SNF and 76.0% (n =
      19/25) of LTC pharmacy medication lists. A total of 191 medication discrepancies
      were identified across all SNF and LTC pharmacy records. Of the 69 SNF staff
      interviewed, 20.3% (n = 14) reported patient care delays due to omitted documents
      during the hospital-to-SNF transition. During interviews, communication between
      the SNF/LTC pharmacy and the discharging hospital was described by facility staff
      as unidirectional with little opportunity for feedback on patient care concerns.
      CONCLUSIONS: The targeted needs assessment guided by the IM framework has lent to
      several planned process improvements initiatives to help reduce medication
      discrepancies during the hospital-to-SNF transition as well as improve
      communication between healthcare entities. Opening lines of communication along
      with aligning healthcare entity goals may help prevent medication-related errors.

PMID- 28455195
TI  - A nationwide study of the extent and factors associated with fentanyl use in
      Australia.
AB  - OBJECTIVE: To examine fentanyl utilisation in the Australian community and
      determine the geographic and socio-demographic factors associated with higher
      rates of fentanyl utilisation. METHODS: National sales data (supplied by IMS
      Health) were used to estimate fentanyl utilisation (in pack sales and milligrams)
      in Australia during 2013, mapped to Australian Bureau of Statistics (ABS)
      Statistical Local Areas (SLAs) and Remoteness Areas. Socio-demographic
      characteristics and total population estimates of SLAs were obtained from the
      ABS. SLA-level data on sex, age distribution, income, occupations involving
      physical labour and number of pharmacies, were included in linear regression
      analyses to examine their association with fentanyl use. RESULTS: An estimated
      12.3 kg (or 859,518 packs) of fentanyl was sold across Australia in 2013,
      equating to an average of 0.55 mg/person over the year. Transdermal patches
      accounted for the majority (99%; 850,923 packs) of fentanyl sales. South
      Australia had the highest rate of utilisation per person. Rates of fentanyl
      utilisation were higher among more remote areas in three jurisdictions. Overall,
      higher utilisation rates were observed in SLAs that were less populated (beta
      0.12; p < 0.001) and those with a higher proportion of older people (beta 0.12; p
      < 0.001), low-income households (beta 0.12; p < 0.001) and people working in jobs
      requiring physical labour (beta 0.08; p < 0.05). CONCLUSIONS: Transdermal
      fentanyl patches account for the majority of fentanyl utilisation in the
      Australian community. There is marked variation in fentanyl utilisation across
      geographic areas, with higher use apparent in areas with a higher proportion of
      older people and indicators of greater socio-economic disadvantage.

PMID- 28455197
TI  - From Obamacare to Trumpcare: Implications for Gastroenterologists.

PMID- 28455198
TI  - Residence at Moderate Versus Low Altitude Is Effective at Maintaining Higher
      Oxygen Saturation During Exercise and Reducing Acute Mountain Sickness Following
      Fast Ascent to 4559 m.
AB  - OBJECTIVE: To continuously monitor oxygen saturation (SpO2) by pulse oximeter and
      assess the development of acute mountain sickness (AMS) using the Lake Louise
      Score (LLS) during ascent from 1154 to 4559 m in 2 groups of subjects: 10
      moderate-altitude residents (MAR; >=1000-<=2500 m) and 34 low-altitude residents
      (LAR). MAR are reported to have a lower incidence of AMS during ascent to higher
      altitudes compared with LAR. Whether this is related to higher SpO2 is still open
      to debate. METHODS: Seventy subjects were recruited; 24-hour SpO2 monitoring with
      finger pulse oximetry was performed. All subjects rode a cable car from 1154 to
      3275 m and then climbed to 3647 m, where 60 subjects (LAR) overnighted. The
      second day, 34/60 LAR reached the highest altitude. Ten subjects who lived
      permanently at 1100 to 1400 m (MAR) climbed directly to 4559 m without an
      overnight stop. RESULTS: One LAR was excluded from the analysis because he
      performed a preacclimatization. We compared data of 10 MAR with data of 33 LAR
      who reached 4559 m. Two MAR had an LLS of 3, and 8 scored <3. Six LAR had an LLS
      of 3 to 4, 8 scored >=5, and 19 scored <3. SpO2 monitoring showed higher mean
      SpO2 in MAR during ascent above 3600 m compared with LAR (MAR, 79+/-4% vs LAR,
      76+/-5%; analysis of variance, P = .03). CONCLUSIONS: The results of this
      preliminary study suggest that residence at moderate altitude allows maintenance
      of higher SpO2 and reduces risk of developing AMS during rapid ascent to higher
      altitude.

PMID- 28455199
TI  - Upper Body Compression Garment: Physiological Effects While Cycling in a Hot
      Environment.
AB  - OBJECTIVE: The purpose of the present study was to investigate the effects of an
      upper body compression garment (UBCG) on physiologic and perceptual responses
      while cycling in a hot environment. METHODS: Twenty recreational road cyclists
      were pair-matched for age, anthropometric data, and fitness level (VO2max) and
      randomly assigned to a control (CON) group (n=10) of cyclists who wore a
      conventional t-shirt or to a group (n=10) of cyclists who wore UBCG. Test session
      consisted of cycling at a fixed load (~50% VO2max) for 30 minutes at an ambient
      temperature of ~40oC (39.9+/-0.4oC), followed by 10 minutes of recovery. RESULTS:
      Significantly greater (P = .002) rectal temperature (Trec) was observed at the
      end of exercise in the UBCG group (38.3+/-0.2oC) versus CON group (37.9+/-0.3oC).
      Significantly greater heart rate (HR) was observed in the UBCG group at minute 15
      (P = .01) and at the end of exercise (187+/-9 vs 173+/-10 beats/min; P = .004)
      for UBCG and CON, respectively. Furthermore, participants who wore UBCG perceived
      a significantly greater (P = .03) thermal sensation at the end of exercise.
      During recovery HR and Trec remained significantly greater (P < .05) in the UBCG
      group. CONCLUSIONS: The use of an UBCG increased cardiovascular and
      thermoregulatory strain during cycling in a hot environment and did not aid
      during recovery.

PMID- 28455200
TI  - Traumatic Pneumothorax Associated With Penetrating Neck Injury Caused by a
      Stingray: A Case Report.
AB  - We describe a patient with missed traumatic pneumothorax due to penetrating neck
      injury that was presumably caused by a stingray while diving. The barb can result
      in significant injuries to deep structures and organs despite a deceptively small
      entrance wound. This case underscores the importance of performing a thorough
      examination and having a high suspicion of distant injury in patients with
      penetrating neck injuries.

PMID- 28455201
TI  - Erratum in Wilderness Environ Med. 2016.

PMID- 28455196
TI  - Maternal IL-17A in autism.
AB  - Although autism spectrum disorder (ASD) has a strong genetic basis, its etiology
      is complex, with several genetic factors likely to be involved as well as
      environmental factors. Immune dysregulation has gained significant attention as a
      causal mechanism in ASD pathogenesis. ASD has been associated with immune
      abnormalities in the brain and periphery, including inflammatory disorders and
      autoimmunity in not only the affected individuals but also their mothers.
      Prenatal exposure to maternal immune activation (MIA) has been implicated as an
      environmental risk factor for ASD. In support of this notion, animal models have
      shown that MIA results in offspring with behavioral, neurological, and
      immunological abnormalities similar to those observed in ASD. This raises the
      question of how MIA exposure can lead to ASD in susceptible individuals. Recent
      evidence points to a potential inflammation pathway linking MIA-associated ASD
      with the activity of T helper 17 (Th17) lymphocytes and their effector cytokine
      interleukin-17A (IL-17A). IL-17A has been implicated from human studies and
      elevated IL-17A levels in the blood have been found to correlate with phenotypic
      severity in a subset of ASD individuals. In MIA model mice, elevated IL-17A
      levels also have been observed. Additionally, antibody blockade to inhibit IL-17A
      signaling was found to prevent ASD-like behaviors in offspring exposed to MIA.
      Therefore, IL-17A dysregulation may play a causal role in the development of ASD.
      The source of increased IL-17A in the MIA mouse model was attributed to maternal
      Th17 cells because genetic removal of the transcription factor RORgammat to
      selectively inhibit Th17 differentiation in pregnant mice was able to prevent ASD
      like behaviors in the offspring. Similar to ASD individuals, the MIA-exposed
      offspring also displayed cortical dysplasia which could be prevented by
      inhibition of IL-17A signaling in pregnant mice. This finding reveals one
      possible cellular mechanism through which ASD-related cognitive and behavioral
      deficits may emerge following maternal inflammation. IL-17A can exert strong
      effects on cell survival and differentiation and the activity of signal
      transduction cascades, which can have important consequences during cortical
      development on neural function. This review examines IL-17A signaling pathways in
      the context of both immunity and neural function that may contribute to the
      development of ASD associated with MIA.

PMID- 28455202
TI  - Don't Kick the Coral!

PMID- 28455203
TI  - Deuterium kinetic isotope effect (DKIE) in copper-induced LDL peroxidation:
      Interrelated effects of on inhibition and propagation.
AB  - LDL peroxidation plays a major role in many physiological and pathophysiological
      processes. The mechanisms of LDL peroxidation induced by transition metal ions
      have therefore been studied intensively. It has been proposed that the mechanism
      involves free radical production that occurs via decomposition of hydroperoxides.
      This, in turn, requires the cleavage of O-H bonds. Cleavage of O-D bond is slower
      and comparison of the kinetics in D2O to the kinetics in H2O is therefore a
      straightforward way to test this aspect of the alleged mechanism. The kinetics of
      peroxidation exhibit marked deuterium kinetic isotope effects at all the stages
      of oxidation under all the studied conditions. We found that the rate of
      propagation of copper-induced peroxidation is a monotonically decreasing function
      of D2O fraction in D2O/H2O mixtures. The only elementary reaction that involves
      "exchangeable" hydrogen at this stage is copper-induced decomposition of
      conjugated hydroperoxides. Therefore, we conclude that the latter step is rate
      limiting reaction including cleavage of oxygen-hydrogen bond of hydroperoxide.
      The lag preceding rapid peroxidation exhibits a biphasic dependence on the
      fraction of D2O. This may be understood on the basis of the effect of
      substituting hydrogen atoms by deuterium. Specifically, such substitution is
      expected to decrease both the rate of initiation of peroxidation and the potency
      of the antioxidant. We interpret our results in terms of the effects of isotopic
      substitution on the rates of the reactions that involve the abstraction of
      "exchangeable" hydrogen atoms of OH groups in tocopherol and hydroperoxides.

PMID- 28455204
TI  - Light-controlled gene expression in yeast using photocaged Cu2.
AB  - The manipulation of cellular function, such as the regulation of gene expression,
      is of great interest to many biotechnological applications and often achieved by
      the addition of small effector molecules. By combining effector molecules with
      photolabile protecting groups that mask their biological activity until they are
      activated by light, precise, yet minimally invasive, photocontrol is enabled.
      However, applications of this trendsetting technology are limited by the small
      number of established caged compound-based expression systems. Supported by
      computational chemistry, we used the versatile photolabile chelator DMNP-EDTA,
      long-established in neurobiology for photolytic Ca2+ release, to control Cu2+
      release upon specific UV-A irradiation. This permits light-mediated control over
      the widely used Cu2+-inducible pCUP1 promoter from S. cerevisiae and thus
      constitutes the first example of a caged metal ion to regulate recombinant gene
      expression. We screened our novel DMNP-EDTA-Cu system for best induction time and
      expression level of eYFP with a high-throughput online monitoring system equipped
      with an LED array for individual illumination of every single well. Thereby, we
      realized a minimally invasive, easy-to-control, parallel and automated optical
      expression regulation via caged Cu2+ allowing temporal and quantitative control
      as a beneficial alternative to conventional induction via pipetting CuCl2 as
      effector molecule.

PMID- 28455205
TI  - Meningococcal disease in the Middle East and Africa: Findings and updates from
      the Global Meningococcal Initiative.
AB  - The Global Meningococcal Initiative (GMI) has recently considered current issues
      in Middle Eastern and African countries, and produced two recommendations: (i)
      that vaccination of attendees should be considered for some types of mass
      gathering events, as some countries mandate for the Hajj, and (ii) vaccination of
      people with human immunodeficiency virus should be used routinely, because of
      increased meningococcal disease (MD) risk. Differences exist between Middle
      Eastern and African countries regarding case and syndrome definitions,
      surveillance, and epidemiologic data gaps. Sentinel surveillance provides an
      overview of trends and prevalence of different capsular groups supporting vaccine
      selection and planning, whereas cost-effectiveness decisions require
      comprehensive disease burden data, ideally counting every case. Surveillance data
      showed importance of serogroup B MD in North Africa and serogroup W expansion in
      Turkey and South Africa. Success of MenAfriVac(r) in the African "meningitis
      belt" was reviewed; the GMI believes similar benefits may follow development of a
      low-cost meningococcal pentavalent vaccine, currently in phase 1 clinical trial,
      by 2022. The importance of carriage and herd protection for controlling invasive
      MD and the importance of advocacy and awareness campaigns were also highlighted.

PMID- 28455206
TI  - Mucoadhesive properties of low molecular weight chitosan- or glycol chitosan- and
      corresponding thiomer-coated poly(isobutylcyanoacrylate) core-shell
      nanoparticles.
AB  - The aim of the present work was to evaluate the mucoadhesive properties of
      poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles (NPs) coated with Low
      Molecular Weight (LMW) chitosan (CS)- and glycol chitosan (GCS)-based thiomers as
      well as with the corresponding LMW unmodified polysaccharides. For this purpose,
      all the CS- and GCS-based thiomers were prepared under simple and mild conditions
      starting from the LMW unmodified polymers CS and GCS. The resulting NPs were of
      spherical shape with diameters ranging from 400 to 600nm and 187 to 309nm, for CS
      and GCS-based NPs, respectively. The mucoadhesive characteristics of these core
      shell NPs were studied in Ussing chambers measuring the percentage of NPs stuck
      on the mucosal of fresh intestinal tissue after 2h of incubation. Moreover,
      incubation of nanoparticle formulations with the intestinal tissue induced
      changes in transmucosal electrical resistance which were measured to gain
      information into the opening of tight junctions and to control the integrity of
      the mucosa. Thus, it was found that PIBCA NPs coated with the GCS-Glutathione
      conjugate (GCGPIBCA NPs) possessed the most favorable mucoadhesive performances.
      Moreover, both GCGPIBCA- and GCS-N-acetyl-cysteine (GCNPIBCA)-core-shell NPs
      might induced an enlargement of the epithelial cell tight junctions. In
      conclusion, coating of PIBCA NPs with GCS-based thiomers may be useful for
      improving the mucoadhesive and permeation properties of these nanocarriers.

PMID- 28455207
TI  - Role of regional absorption and gastrointestinal motility on variability in oral
      absorption of a model drug.
AB  - Variability in oral absorption in pre-clinical species makes human dose
      projection challenging. In this study, we investigated the mechanistic basis of
      variability in oral absorption of a model hydrophobic compound with pH-dependent
      solubility, BMS-955829, after oral dosing in rats, dogs, and cynomolgus monkeys.
      The contribution of regional absorption to pharmacokinetic variability was
      assessed in ported monkeys by direct intraduodenal and intraileal administration.
      The effect of BMS-955829 on gastric emptying and intestinal motility was
      investigated by radiography after co-administration of barium. BMS-955829
      exhibited species dependent oral bioavailability, with high variability in
      monkeys. During regional absorption studies, highest rate of drug absorption was
      observed after direct intraduodenal administration. Radiography studies indicated
      that BMS-955829 slowed gastric emptying and intestinal motility. The effect of
      rate and site of drug release on oral exposure was studied using different drug
      product formulations. Reducing the rate of drug release reduced oral exposure
      variability without compromising exposure in cynomolgus monkeys. This effect was
      likely mediated by avoidance of rapid initial absorption and drug effect on
      gastric emptying and intestinal transit within the biorelevant timeframe. Thus,
      drug release rate can modulate the effect of physiological factors on variability
      in the oral absorption of sensitive compounds.

PMID- 28455208
TI  - Soap production: A green prospective.
AB  - A green prospective based on the reuse of waste materials such as almond shells,
      orange peel and used cooking oil to manufacture soap is presented. In Portugal,
      thousands of tons of waste are generated from used cooking oil and production of
      nut shells' residues is growing every year. In addition, the high consumption of
      citrus fruits, oranges in particular, generates large amounts of citrus peel.
      Therefore, it is necessary to diversify reuse mechanisms of these wastes, in
      order to make them back into raw materials. Complying with this trend, this work
      was carried out by processing and grinding almond shells, treating used oil,
      processing orange peels and extracting limonene, formulating and producing soap,
      and performing an acceptance study of the final product. Results validated a high
      potential of the idea in the field of environmental education, so it can be
      replicated in practical classes. It can also be useful for waste management, and
      it can support the development of community projects on an ecological approach.

PMID- 28455209
TI  - A dynamic model for organic waste management in Quebec (D-MOWIQ) as a tool to
      review environmental, societal and economic perspectives of a waste management
      policy.
AB  - A dynamic systems model of organic waste management for the province of Quebec,
      Canada, was built. Six distinct modules taking into account social, economical
      and environmental issues and perspectives were included. Five scenarios were
      designed and tested to identify the potential consequences of different
      governmental and demographic combinations of decisions over time. Among these
      scenarios, one examines Quebec's organic waste management policy (2011-2015),
      while the other scenarios represent business as usual or emphasize ecology,
      economy or social benefits in the decision-making process. Model outputs suggest
      that the current governmental policy should yield favorable environmental
      benefits, energy production and waste valorization. The projections stemming from
      the current policy action plan approach the benefits gained by another scenario
      emphasizing the environmental aspects in the decision-making process. As
      expected, without the current policy and action plan in place, or business as
      usual, little improvements are expected in waste management compared to current
      trends, and strictly emphasizing economic imperatives does not favor sustainable
      organic waste management.

PMID- 28455210
TI  - Low temperature circulating fluidized bed gasification and co-gasification of
      municipal sewage sludge. Part 1: Process performance and gas product
      characterization.
AB  - Results from five experimental campaigns with Low Temperature Circulating
      Fluidized Bed (LT-CFB) gasification of straw and/or municipal sewage sludge (MSS)
      from three different Danish municipal waste water treatment plants in pilot and
      demonstration scale are analyzed and compared. The gasification process is
      characterized with respect to process stability, process performance and gas
      product characteristics. All experimental campaigns were conducted at maximum
      temperatures below 750 degrees C, with air equivalence ratios around 0.12 and
      with pure silica sand as start-up bed material. A total of 8600kg of MSS dry
      matter was gasified during 133h of operation. The average thermal loads during
      the five experiments were 62-100% of nominal capacity. The short term stability
      of all campaigns was excellent, but gasification of dry MSS lead to substantial
      accumulation of coarse and rigid, but un-sintered, ash particles in the system.
      Co-gasification of MSS with sufficient amounts of cereal straw was found to be an
      effective way to mitigate these issues as well as eliminate thermal MSS drying
      requirements. Characterization of gas products and process performance showed
      that even though gas composition varied substantially, hot gas efficiencies of
      around 90% could be achieved for all MSS fuel types.

PMID- 28455211
TI  - Comparison of intratesticular lidocaine, sacrococcygeal epidural lidocaine and
      intravenous methadone in cats undergoing castration: a prospective, randomized,
      investigator-blind clinical trial.
AB  - OBJECTIVE: The objective of this study was to compare three analgesic protocols
      for feline castration. STUDY DESIGN: Prospective, randomized clinical study.
      ANIMALS: Forty-nine client-owned cats. METHODS: Cats were injected with
      intramuscular (IM) dexmedetomidine (15 MUg kg-1) and alfaxalone (3 mg kg-1) and
      assigned randomly to one of three treatment groups. Group ITL (n = 15) were
      administered intratesticular 2% lidocaine (0.05 mL each testicle), group SCL (n =
      15) a sacrococcygeal epidural injection of 2% lidocaine (0.1 mL kg-1) and group
      IVM (n = 19) intravenous (IV) methadone (0.3 mg kg-1), before surgery.
      Cardiorespiratory variables were recorded. In case of autonomic nociceptive
      response, IV fentanyl (2 MUg kg-1) was administered. During recovery, time from
      IM atipamezole (75 MUg kg-1, administered at the end of surgery) to sternal
      recumbency and to active interaction was recorded. Quality of recovery was
      assessed using a simple descriptive scale. Postoperative analgesia was evaluated
      using a visual analogue scale and the UNESP-Botucatu multidimensional composite
      pain scale (MCPS) at return of active interaction and then 1, 2 and 3 hours
      later. RESULTS: The three analgesic protocols were comparable in terms of
      intraoperative fentanyl and propofol requirement. Cardiorespiratory variables
      stayed within normal ranges in the majority of the cases, although group IVM had
      the lowest intraoperative respiratory rate (p = 0.0009). No differences were
      detected between groups in UNESP-Botucatu MCPS scores (p = 0.21). However, group
      ITL showed higher visual analogue scale score than group IVM (p = 0.001). Four
      cats enrolled in group ITL, as well as three of group SCL and one of group IVM,
      required rescue analgesics before the completion of pain assessment. CONCLUSIONS
      AND CLINICAL RELEVANCE: Intratesticular and sacrococcygeal epidural lidocaine
      injections could be regarded as good alternatives to systemic opioids in cats
      undergoing castration, although the benefits of these techniques seem to be of
      shorter duration than IV methadone.

PMID- 28455212
TI  - Cardiovascular effects and intraoperative pharmacokinetics of tramadol in sheep
      undergoing spinal surgery.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of two doses of tramadol during
      isoflurane anaesthesia in sheep and their ability to prevent the cardiovascular
      response induced by surgical stimulation. STUDY DESIGN: Prospective randomized
      controlled study. ANIMALS: A total of 12 healthy sheep (mean weight, 47.5+/-7.9
      kg) undergoing lumbar transpedicular intervertebral disk nucleotomy. METHODS:
      Sheep were sedated with medetomidine, anaesthesia was induced with propofol and
      maintained with isoflurane at 1.5 vol.%. Baseline heart rate and blood pressure
      were measured and sheep were randomly assigned an intravenous injection of
      tramadol (4 or 6 mg kg-1). Fentanyl was injected as rescue analgesic if
      cardiovascular parameters were increased more than 20% compared to baseline. If
      those variables were below 20% of baseline, the concentration of isoflurane was
      gradually decreased until parameters returned to the original value. Blood
      collections were performed at pre-assigned times, and concentrations of tramadol
      and O-desmethyltramadol (M1) assessed by high-performance liquid chromatography.
      RESULTS: Time from premedication to anaesthesia induction, anaesthesia time,
      propofol dose and intraoperative body temperature were similar between doses.
      Cardiovascular variables remained between +/-20% of baseline value, and no
      statistical difference was observed between treatments. Regardless of the dose of
      tramadol administered, arterial blood pressure was statistically higher than
      baseline 10 minutes after tramadol administration, but it gradually returned to
      previous values. A two-compartment model and a non-compartment model described
      the pharmacokinetics of tramadol and M1, respectively. Plasma concentrations of
      tramadol rapidly decreased in the first 2 hours for both doses with an
      elimination half-life of more than 40 minutes. The M1 maximum concentration was
      similar for both doses, and it was detected in plasma after 35 minutes.
      CONCLUSIONS AND CLINICAL RELEVANCE: Both doses of tramadol provided adequate
      cardiovascular stability during spinal surgery in sheep. The pharmacokinetic
      variables may be used to plan the dosage regime during general anaesthesia.

PMID- 28455213
TI  - Localization of zinc transporters in the spinal cord of cynomolgus monkey.
AB  - Zinc is abundant in the spinal cord, where it participates in several
      physiological and pathophysiological processes, including neurotransmission,
      spinal cord injury, and amyotrophic lateral sclerosis. However, the mechanisms
      underlying zinc homeostasis in the spinal cord are largely unknown. Zinc
      transporters (ZnTs) are responsible for transporting zinc from the cytoplasm to
      the extracellular space or to intracellular compartments. In the present study,
      we examined the distribution of ZnT1-10 proteins in the spinal cord of cynomolgus
      monkey. Immunohistochemical studies demonstrate that all detected ZnT family
      members are expressed in the gray matter. ZnT1-10 immunoreactivity can be seen in
      both motor and sensory neurons in the dorsal and ventral horn from the cervical
      to sacral segments. No obvious immunostaining was found in the glia cells. The
      present study demonstrates that ZnT proteins are functionally important for
      regulating zinc metabolism in both motor and sensory functions in monkey spinal
      cord.

PMID- 28455214
TI  - Conserved signaling pathways underlying heterotopic ossification.
AB  - Heterotopic ossification (HO), a serious disorder of extra-skeletal bone
      formation, occurs as a common complication of trauma or in rare genetic
      disorders. Many conserved signaling pathways have been implicated in HO; however,
      the exact underlying molecular mechanisms for many forms of HO are still unclear.
      The emerging picture is that dysregulation of bone morphogenetic protein (BMP)
      signaling plays a central role in the process, but that other conserved signaling
      pathways, such as Hedgehog (HH), Wnt/beta-catenin and Fibroblast growth factors
      (FGF), are also involved, either through cross-talk with BMP signaling or through
      other independent mechanisms. Deep understanding of the conserved signaling
      pathways is necessary for the effective prevention and treatment of HO. In this
      review, we update and integrate recent progress in this area. Hopefully, our
      discussion will point to novel promising, druggable loci for further
      translational research and successful clinical applications.

PMID- 28455215
TI  - Effect of the lipoxygenase-inhibitors baicalein and zileuton on the vertebra in
      ovariectomized rats.
AB  - Osteoporosis is one of the most common diseases worldwide. In osteoporosis,
      vertebral fractures represent a major burden. Lipoxygenase (LOX) inhibitors such
      as baicalein and zileuton may represent a promising therapeutic option owing to
      their antioxidative effects and suppression of various inflammatory processes in
      muscle and bone. The effect of these LOX inhibitors on the spine was studied in
      osteopenic rats. Female Sprague-Dawley rats were divided two times into five
      groups: four groups each were ovariectomized (OVX) and one control group was non
      ovariectomized (NON-OVX). Eight weeks after ovariectomy, three concentrations of
      baicalein (1mg/kg body weight [BW], 10mg/kgBW, and 100mg/kgBW) were administered
      subcutaneously daily in three OVX groups for 4weeks. Similarly, zileuton was
      administered in three concentrations via food for 5weeks. In vivo computed
      tomography (pQCT) of the spine was performed before the treatments and at the end
      of the experiment. Lumbar vertebrae were subjected to a compression test, micro
      CT, and ashing analyses. After baicalein treatment, cortical bone mineral density
      (BMD) was improved; trabecular connectivity and trabecular BMD were diminished at
      high dose. After zileuton treatment, the total BMD, anorganic weight, trabecular
      nodes, and trabecular area were improved. The in vivo stress-strain index was
      increased and alkaline phosphatase activity in serum was enhanced after both
      treatments. A dose-dependent effect was not clearly observed after both
      treatments. The treatments using baicalein for 4 and zileuton for 5weeks were not
      sufficient to change the biomechanical properties and bone volume fraction
      (BV/TV). Overall, baicalein improved the cortical bone parameters whereas
      zileuton had a favorable effect on the trabecular structure. Moreover, both
      treatments increased the bone formation rate. Longer trials, a combination of
      both LOX inhibitors, and their effect at the cellular and molecular levels should
      be investigated in further studies.

PMID- 28455216
TI  - Impairment of the type I interferon response by HIV-1: Potential targets for HIV
      eradication.
AB  - By interfering with the type I interferon (IFN1) response, human immunodeficiency
      virus 1 (HIV-1) can circumvent host antiviral signalling and establish persistent
      viral reservoirs. HIV-1-mediated defects in the IFN pathway are numerous, and
      include the impairment of protein receptors involved in pathogen detection,
      downstream signalling cascades required for IFN1 upregulation, and expression or
      function of key IFN1-inducible, antiviral proteins. Despite this, the activation
      of IFN1-inducible, antiviral proteins has been shown to facilitate the killing of
      latently HIV-infected cells in vitro. Understanding how IFN1 signalling is
      blocked in physiologically-relevant models of HIV-1 infection, and whether these
      defects can be reversed, is therefore of great importance for the development of
      novel therapeutic strategies aimed at eradicating the HIV-1 reservoir.

PMID- 28455217
TI  - Subthalamic nucleus deep brain stimulation for the treatment of secondary
      dystonia: A case series and review of literature.

PMID- 28455218
TI  - Age-dependent functional crosstalk between cardiac fibroblasts and cardiomyocytes
      in a 3D engineered cardiac tissue.
AB  - : Complex heterocellular interactions between cardiomyocytes and fibroblasts in
      the heart involve their bidirectional signaling via cell-cell contacts, paracrine
      factors, and extracellular matrix (ECM). These interactions vary with heart
      development and pathology leading to changes in cardiac structure and function.
      Whether cardiac fibroblasts of different ages interact differentially with
      cardiomyocytes to distinctly impact their function remains unknown. Here, we
      explored the direct structural and functional effects of fetal and adult cardiac
      fibroblasts on cardiomyocytes using a tissue-engineered 3D co-culture system. We
      show that the age of cardiac fibroblasts is a strong determinant of the
      structure, function, and molecular properties of co-cultured tissues. In
      particular, in vitro expanded adult, but not fetal, cardiac fibroblasts
      significantly deteriorated electrical and mechanical function of the co-cultured
      cardiomyocytes, as evidenced by slower action potential conduction, prolonged
      action potential duration, weaker contractions, higher tissue stiffness, and
      reduced calcium transient amplitude. This functional deficit was associated with
      structural and molecular signatures of pathological remodeling including
      fibroblast proliferation, interstitial collagen deposition, and upregulation of
      pro-fibrotic markers. Our studies imply critical roles of the age of supporting
      cells in engineering functional cardiac tissues and provide a new physiologically
      relevant in vitro platform to investigate influence of heterocellular
      interactions on cardiomyocyte function, development, and disease. STATEMENT OF
      SIGNIFICANCE: Previous studies have shown that cardiomyocytes and fibroblasts in
      the heart interact through direct contacts, paracrine factors, and matrix
      mediated crosstalk. However, whether cardiac fibroblasts of different ages
      distinctly impact cardiomyocyte function remains elusive. We employed a tissue
      engineered hydrogel-based co-culture system to study interactions of
      cardiomyocytes with fetal or adult cardiac fibroblasts. We show that the age of
      cardiac fibroblasts is a strong determinant of the structure, function, and
      molecular properties of engineered cardiac tissues and that key features of
      fibrotic myocardium are replicated by supplementing cardiomyocytes with expanded
      adult but not fetal fibroblasts. These findings relate to implantation of stem
      cell-derived cardiomyocytes in adult myocardium and warrant further studies of
      how age and source of non-myocytes impact cardiac function and maturation.

PMID- 28455220
TI  - Site-specific characterization of beetle horn shell with micromechanical bending
      test in focused ion beam system.
AB  - : Biological materials are the result of years of evolution and possess a number
      of efficient features and structures. Researchers have investigated the
      possibility of designing biomedical structures that take advantage of these
      structural features. Insect shells, such as beetle shells, are among the most
      promising types of biological material for biomimetic development. However, due
      to their intricate geometries and small sizes, it is challenging to measure the
      mechanical properties of these microscale structures. In this study, we developed
      an in-situ testing platform for site-specific experiments in a focused ion beam
      (FIB) system. Multi-axis nano-manipulators and a micro-force sensor were utilized
      in the testing platform to allow better results in the sample preparation and
      data acquisition. The entire test protocol, consisting of locating sample, ion
      beam milling and micro-mechanical bending tests, can be carried out without
      sample transfer or reattachment. We used our newly devised test platform to
      evaluate the micromechanical properties and structural features of each separated
      layer of the beetle horn shell. The Young's modulus of both the exocuticle and
      endocuticle layers was measured. We carried out a bending test to characterize
      the layers mechanically. The exocuticle layer bent in a brick-like manner, while
      the endocuticle layer exhibited a crack blunting effect. STATEMENT OF
      SIGNIFICANCE: This paper proposed an in-situ manipulation/test method in focused
      ion beam for characterizing micromechanical properties of beetle horn shell. The
      challenge in precise and accurate fabrication for the samples with complex
      geometry was overcome by using nano-manipulators having multi-degree of freedom
      and a micro-gripper. With the aid of this specially designed test platform,
      bending tests were carried out on cantilever-shaped samples prepared by focused
      ion beam milling. Structural differences between exocuticle and endocuticle
      layers of beetle horn shell were explored and the results provided insight into
      the structural advantages of each biocomposite structure.

PMID- 28455219
TI  - pH-sensitive polymeric nanoparticles for co-delivery of doxorubicin and curcumin
      to treat cancer via enhanced pro-apoptotic and anti-angiogenic activities.
AB  - : Co-delivery of multiple drugs with complementary anticancer mechanisms by nano
      carriers offers an effective strategy to treat cancer. The combination of drugs
      with pro-apoptotic and anti-angiogenic activities is potentially effective in
      treating human hepatocellular carcinoma (HCC). Herein, we developed a co-delivery
      system for doxorubicin (Dox), a pro-apoptotic drug, and curcumin (Cur), a potent
      drug for antiangiogenesis, in pH-sensitive nanoparticles (NPs) constituted with
      amphiphilic poly(beta-amino ester) copolymer. Dox & Cur co-loaded NPs ((D+C)/NPs)
      were prepared with optimized drug ratio, showing low polydispersity, high
      encapsulation efficiency, and enhanced release in the acidic environment of
      cancer cells. Furthermore, enhanced cellular internalization of cargoes delivered
      from (D+C)/NPs were observed in human liver cancer SMMC 7721 cells and human
      umbilical vein endothelial cells (HUVECs) compared to the use of free drugs. The
      (D+C)/NPs induced a high rate of apoptosis in SMMC 7721 cells through decreased
      mitochondrial membrane potential. Additionally, (D+C)/NPs exhibited stronger anti
      angiogenic effects including inhibition of HUVEC proliferation, migration,
      invasion, and tube formation mediated VEGF pathway modulation in vitro and in
      vivo. Taken together, encapsulation of the pro-apoptotic drug Dox and
      antiangiogenic agent Cur in pH-sensitive NPs provides a promising strategy to
      effectively inhibit HCC progression in a synergistic manner. STATEMENT OF
      SIGNIFICANCE: The combination of multiple drugs has been demonstrated to be more
      effective than single treatment. However, the different physicochemical and
      pharmacokinetic profiles of each drug render optimal delivery challenging. In
      view of the great delivery advantage of nanocarriers to unify the multiple drugs
      in vivo, stimulus-responsive nano-carriers are more crucial to increase efficacy
      and reduce toxicity from off-target exposure. Therefore, herein the pH-sensitive
      nanoparticles, composed by d-alpha-tocopheryl polyethylene glycol 1000-block-poly
      (beta-amino ester) (TPGS-PAE) polymers, have been fabricated for doxorubicin
      (Dox) and curcumin (Cur) co-delivery, which exhibited diverse anticancer
      approaches, i.e. pro-apoptosis and antiangiogenesis. The precise intracellular
      target site and effective drug combination concentration result in the enhanced
      antitumor efficiency and the reduced systematic toxicity of Dox. The co
      encapsulation of the pro-apoptotic drug and antiangiogenic agent in pH-sensitive
      NPs provides a promising strategy to effectively inhibit malignant neoplasm
      progression in a synergistic manner.

PMID- 28455221
TI  - An increase in sexually transmitted infections seen in US emergency departments.
AB  - Surveillance data show that there is an increase in the incidence of sexually
      transmitted infections (STI) and we believe that because of this increased
      incidence, coupled with a deteriorating public health infrastructure, these STIs
      are being seen more often in emergency departments. Therefore, we used six years
      of the most recently available nationally-representative emergency department
      data to show an increase in the number of emergency department visits where a
      sexually transmitted infection was treated. We further described the population
      for these visits.

PMID- 28455222
TI  - Rising longitudinal trajectories in suicide rates: The role of firearm suicide
      rates and firearm legislation.
AB  - Firearms account for approximately half of all US suicide deaths each year
      despite being utilized in only a small minority of suicide attempts. We examined
      the extent to which overall suicide rates fluctuated relative to firearm and non
      firearm suicide rates across a period of 16years (1999-2015). We further tested
      the notion of means substitution by examining the association between firearm
      suicide rates and non-firearm suicide rates. Lastly, we examined the extent to
      which the presence of specific laws related to handgun ownership previously shown
      cross-sectionally to be associated with lower suicide rates (universal background
      checks, mandatory waiting periods) were associated with an attenuated trajectory
      in suicide rates across the study period. As anticipated, whereas decreases in
      firearm suicide rates were associated with decreases in overall suicide rates
      (b=0.46, SE=0.07, p<0.001), decreases in firearm suicides were not associated
      with off-setting increases in suicides by other methods (b=-0.04, SE=0.05,
      p=0.36). Furthermore, the absence of universal background check (b=0.12, SE=0.05,
      p=0.028) and mandatory waiting period (b=0.16, SE=0.06, p=0.008) laws was
      associated with a more steeply rising trajectory of statewide suicide rates.
      These results mitigate concerns regarding means substitution and speak to the
      potential high yield impact of systematically implemented means safety prevention
      efforts focused on firearms.

PMID- 28455223
TI  - A longitudinal assessment of adherence to breast and cervical cancer screening
      recommendations among women with and without intellectual disability.
AB  - Each year in the United States, about 4000 deaths are attributed to cervical
      cancer, and over 40,000 deaths are attributed to breast cancer (U.S. Cancer
      Statistics Working Group, 2015). The purpose of this study was to identify
      predictors of full, partial, and no screening for breast and cervical cancer
      among women with and without intellectual disability (ID) who are within the age
      group for screening recommended by the U.S. Preventive Service Task Force
      (USPSTF), while accounting for changes in recommendations over the study period.
      Women with ID and an age matched comparison group of women without ID were
      identified using merged South Carolina Medicaid and Medicare files from 2000 to
      2010. The sample consisted of 9406 and 16,806 women for mammography screening and
      Papanicolaou (Pap) testing adherence, respectively. We estimated multinomial
      logistic regression models and determined that women with ID were significantly
      less likely than women without ID to be fully adherent compared to no screening
      with mammography recommendations (adjusted odds ratio [AOR]: 0.63, 95% confidence
      interval [CI] 0.55-0.72), and Pap testing recommendations (AOR: 0.17, 95% CI 0.16
      0.19). For the 70% of women with ID for whom we had residential information,
      those who lived in a group home, medical facility, or supervised community living
      setting were more likely to be fully adherent with both preventive services than
      those living alone or with family members. For both outcomes, women residing in a
      supervised nonmedical community living setting had the highest odds of full
      adherence, adjusting for other covariates.

PMID- 28455224
TI  - Comparison of anthropometric measurements associated with the risk of endoscopic
      erosive esophagitis: A cross-sectional study.
AB  - BACKGROUND: In this cross-sectional study, we assessed five anthropometric
      measurements to determine the most reliable indicator of the erosive esophagitis
      (EE) risk: body mass index (BMI), waist circumference (WC), waist to height ratio
      (WHtR), a body shape index (ABSI), and body roundness index (BRI). METHODS: This
      study included 182,407 participants who underwent an esophagogastroduodenoscopy
      as part of a routine health check-up. We used the area under the receiver
      operating characteristic curve (AUC) to assess the discriminatory power of each
      anthropometric measure as an indicator of EE risk. RESULTS: The prevalence of EE
      increased per quartile for all five anthropometric measurements in patients of
      both sexes (1st quartile vs. 4th quartile, all P<0.05). ABSI had the lowest AUCs
      for EE in both sexes (AUC: 0.524, 95% CI: 0.519-0.529 for male patients; AUC:
      0.524, 95% CI: 0.513-0.535 for female patients). In contrast, BRI was the best
      predictor of EE in male patients (OR: 2.095, 95% CI: 1.982-2.215, P<0.0001), and
      WC was the best predictor of EE in female patients (OR: 2.028, 95% CI: 1.785
      2.307, P<0.0001). WC showed the highest AUC values for EE in both male patients
      (AUC: 0.571, 95% CI: 0.566-0.576) and female patients (AUC: 0.596, 95% CI: 0.585
      0.608). CONCLUSIONS: BRI and WC were the most relevant indicators of EE risk in
      male and female patients, respectively. ABSI was the least reliable indicator of
      EE risk in patients of both sexes.

PMID- 28455225
TI  - Temporal and spatiotemporal variability in comprehensive forearm skin
      microcirculation assessment during occlusion protocols.
AB  - Forearm skin hyperemia during release after brachial occlusion has been proposed
      for evaluating peripheral arterial disease and endothelial dysfunction. We used a
      novel fiberoptic system integrating Laser Doppler Flowmetry and Diffuse
      Reflectance Spectroscopy for a comprehensive pointwise model based
      microcirculation characterization. The aim was to evaluate and compare the
      temporal and the spatiotemporal variabilities in forearm skin microcirculation
      parameters (speed resolved perfusion; low speed <1mm/s, PerfSR, <1; mid-speed 1
      10mm/s, high speed >10mm/s, and total perfusion (PerfSR, tot); the concentration
      and oxygenation of red blood cells, CRBC and SO2). Ten healthy subjects underwent
      arterial and venous forearm occlusions (AO, VO), repeated within one week. The
      repeatability was calculated as the coefficient of variation (CV) and the
      agreement as the intra-class correlation coefficient (ICC). The temporal CVs for
      conventional perfusion, Perfconv, PerfSR, tot, CRBC and SO2 were 14%, 12%, 9% and
      9%, respectively, while the ICC were >0.75 (excellent). The perfusion measures
      generally had a higher spatiotemporal than temporal variability, which was not
      the case for SO2 and CRBC. The corresponding spatiotemporal CVs were 33%, 32%,
      18% and 15%, respectively. During VO, CRBC had a CV<35% and ICC>0.40 (fair-good),
      and after release this was the case for CRBC (AO and VO), SO2 (VO) and PerfSR, <1
      (VO). In conclusion, the skin microcirculation parameters showed excellent
      temporal repeatability, while the spatiotemporal repeatability especially for
      perfusion was poorer. The parameters with acceptable repeatability and fair-good
      agreement were: CRBC during and after release of VO, the PerfSR, <1 after release
      of VO, the SO2 and the CRBC after release of AO. However, the value of these
      parameters in discriminating endothelial function remains to be studied.

PMID- 28455226
TI  - The effect of selective opioid receptor agonists and antagonists on epileptiform
      activity in morphine-dependent infant mice hippocampal slices.
AB  - Hippocampal slices of mouse brain were used to estimate how selective agonist and
      antagonist of opioid receptors alter Low-Mg+2 artificial cerebrospinal fluid (LM
      ACSF)-induced epileptiform activities in normal and morphine-dependent mice.
      Brain slices were obtained from control and morphine-dependent mice. The morphine
      dependent group received morphine once a day for 5 consecutive days, and the
      control group received saline. All injections were administered subcutaneously
      (s.c) in a volume of 0.1mL on postnatal days 14-18. Brain slices were perfused
      with LM-ACSF along with selective agonist and antagonist of MU, kappa and delta
      opioid receptors. Changes in spike count per unit of time were used as indices to
      quantify the effects of LM-ACSF exposure in the slices. In both groups, DAMGO
      (selective MU opioid receptor agonist) and DPDPE (selective delta opioid receptor
      agonist) suppressed while Dyn-A (selective kappa opioid receptor agonist)
      potentiated the epileptiform activity. Meanwhile, BFN-A (selective MU opioid
      receptor antagonist) recovered epileptiform activity in normal brain slices but
      not in morphine-dependent ones. NTI (selective delta opioid receptor antagonist)
      and nor-BNI (selective kappa opioid receptor antagonist) decreased epileptiform
      activity. It seems that the excitatory effect of morphine on epileptiform
      activity was mediated through kappa receptors and its inhibitory effect was
      mediated via the mu receptor and, to a lesser degree, through the delta receptor.
      The pattern of effect was similar in normal and morphine-dependent slices, but
      the intensity of the effect was significantly stronger in normal mice. Finding of
      this study might be considered for further research and attention in epilepsy
      treatment.

PMID- 28455227
TI  - Suppression of OGT by microRNA24 reduces FOXA1 stability and prevents breast
      cancer cells invasion.
AB  - O-GlcNAc transferase (OGT) catalyzes the addition of O-GlcNAc to certain serine
      or threonine residue on a wide variety of cytosolic and nuclear proteins and
      regulates cellular activities such as signaling and transcription. Although there
      are emerging evidences that OGT plays important roles in breast cancer
      metastasis, the underlying mechanism is not fully understood. In this study, we
      demonstrated that up-regulation of OGT correlates with breast cancer cells
      invasion. Over-expression of OGT stimulates cells invasion, while OGT silence
      exhibits the opposite effects. OGT is further identified as a target of
      microRNA24 (miR24). miR24 down-regulates OGT expression and subsequently
      suppresses cells invasion. Re-expression of OGT significantly rescues miR24
      mediated invasion repression. Furthermore, our data showed that FOXA1 is
      subjected to O-GlcNAcylation, which instabilizes FOXA1 protein and promotes
      breast cancer cells invasion. In conclusion, our results demonstrated that miR24
      inhibits breast cancer cells invasion by targeting OGT and reducing FOXA1
      stability. These results also indicated that OGT might be a potential target for
      the diagnosis and therapy of breast cancer metastasis.

PMID- 28455228
TI  - Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via
      JNK/p38 MAPK/NF-kappab/Stat3/Bcl-2 signaling pathway.
AB  - Brusatol, isolated from brucea, has been proved to exhibit anticancer influence
      on various kind of human malignancies. However, the role that brusatol plays in
      pancreatic cancer is seldom known by the public. Through researches brusatol was
      proved to inhibit growth and induce apoptosis in both PATU-8988 and PANC-1 cells
      by decreasing the expression level of Bcl-2 and increasing the expression levels
      of Bax, Cleaved Caspase-3. Then we found the activation of the JNK, p38 MAPK and
      inactivation of the NF-kappab, Stat3 are related with the potential pro-apoptotic
      signaling pathways. However, SP600125 could not only abrogated the JNK activation
      caused by brusatol, but also reverse the p38 activation and the decrease of Bcl-2
      as SB203580 did. Besides, SP600125 and SB203580 also reversed the inactivation of
      NF-kappab and Stat3. Furthermore, BAY 11-7082 and S3I-201 indeed had the similar
      effect as brusatol had on the expression of Phospho-Stat3 and Bcl-2. To sum up,
      we came to a conclusion that in pancreatic cancer, brusatol do inhibit growth and
      induce apoptosis. And we inferred that brusatol illustrates anticancer
      attribution via JNK/p38 MAPK/NF-kappab/Stat3/Bcl-2 signaling pathway.

PMID- 28455229
TI  - iTRAQ quantitative proteomic study in patients with thoracic ossification of the
      ligamentum flavum.
AB  - Thoracic ossification of the ligamentum flavum (TOLF) is a unique disease with
      ectopic ossification, and is a major cause of thoracic spinal stenosis and
      myelopathy. However, the underlying etiology remains largely unknown. In this
      study, the ligamentum flavum was systematically analyzed in TOLF patients by
      using comprehensive iTRAQ labeled quantitative proteomics. Among 1285 detected
      proteins, there were 282 proteins identified to be differentially expressed. The
      Gene Ontology (GO) analysis regarding functional annotation of proteins consists
      of the following three aspects: the biological process, the molecular function,
      and the cellular components. The function clustering analysis revealed that ten
      of the above proteins are related to inflammation, such as tumor necrosis factor
      (TNF). This finding was subsequently validated by ELISA, which indicated that
      serum TNF-alpha of TOLF patients was significantly higher compared with the
      control group. To address the effect of TNF-alpha on ossification-related gene
      expression, we purified and cultured primary cells from thoracic ligamentum
      flavum of patients with TOLF. TNF-alpha was then used to stimulate cells. RNA was
      isolated and analyzed by RT-PCR. Our results showed that TNF-alpha was able to
      induce the expressions of osteoblast-specific transcription factor Osterix (Osx)
      in ligamentum flavum cells, suggesting that it can promote osteoblast
      differentiation. In addition, as the Osx downstream osteoblast genes OCN and ALP
      were also activated by TNF-alpha. This is the first proteomic study to identify
      inflammation factors such as TNF-alpha involved in ossified ligamentum flavum in
      TOLF, which may contribute to a better understanding of the cause of TOLF.

PMID- 28455230
TI  - Mangiferin attenuates blast-induced traumatic brain injury via inhibiting NLRP3
      inflammasome.
AB  - There is growing evidence that Mangiferin possess therapeutic benefit during
      neuroinflammation on various brain injury models due to its anti-inflammatory
      properties. It is reported that inflammatory plays a crucial role in the
      pathogenesis of secondary injury induced by the blast-induced traumatic brain
      injury (bTBI). However, the role of mangiferin in bTBI is yet to be studied. In
      our study, the potential effect of mangiferin in the duration of bTBI was
      examined first. Fortunately, the amelioration of cerebral cortex damage was found
      in rats suffering bTBI after mangiferin administration. Furthermore, the detail
      mechanism of mangiferin's beneficial actions in bTBI was also studied. The
      results revealed that mangiferin might alleviate brain damage in rats with bTBI
      by inhibiting the NOD-like receptor family, pyrin domain-containing 3 (NLRP3)
      inflammasome activation, which was accompanied by mangiferin's inhibition of
      oxidative stress and pro-inflammatory cytokines production. Therefore, this
      research allows us to speculate that, for first time, NLRP3 is involved in the
      anti-inflammatory effect of mangiferin in the cerebral cortex, and mangiferin
      could be a potential therapy drug for bTBI.

PMID- 28455231
TI  - Multiple functional attributes of glucose-monitoring neurons in the medial
      orbitofrontal (ventrolateral prefrontal) cortex.
AB  - Multiple functional attributes of glucose-monitoring neurons in the medial
      orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX
      XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons,
      reportedly involved in the central feeding control, exist in the medial
      orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological,
      metabolic and behavioral studies reveal complex functional attributes of these
      cells and raise their homeostatic significance. Single neuron recordings, by
      means of the multibarreled microelectrophoretic technique, elucidate differential
      sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to
      glucose and other chemicals, whereas gustatory stimulations demonstrate their
      distinct taste responsiveness. Metabolic examinations provide evidence for
      alteration of blood glucose level in glucose tolerance test and elevation of
      plasma triglyceride concentration after destruction of the local GM cells by
      streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC
      fails to interfere with the acquisition of saccharin conditioned taste avoidance,
      does cause, however, taste perception deficit in taste reactivity tests. Multiple
      functional attributes of GM neurons in the mVLPFC, within the frame of the
      hierarchically organized central GM neuronal network, appear to play important
      role in the maintenance of the homeostatic balance.

PMID- 28455232
TI  - Bayesian randomized clinical trials: From fixed to adaptive design.
AB  - Randomized controlled studies are the gold standard for phase III clinical
      trials. Using alpha-spending functions to control the overall type I error rate,
      group sequential methods are well established and have been dominating phase III
      studies. Bayesian randomized design, on the other hand, can be viewed as a
      complement instead of competitive approach to the frequentist methods. For the
      fixed Bayesian design, the hypothesis testing can be cast in the posterior
      probability or Bayes factor framework, which has a direct link to the frequentist
      type I error rate. Bayesian group sequential design relies upon Bayesian decision
      theoretic approaches based on backward induction, which is often computationally
      intensive. Compared with the frequentist approaches, Bayesian methods have
      several advantages. The posterior predictive probability serves as a useful and
      convenient tool for trial monitoring, and can be updated at any time as the data
      accrue during the trial. The Bayesian decision-theoretic framework possesses a
      direct link to the decision making in the practical setting, and can be modeled
      more realistically to reflect the actual cost-benefit analysis during the drug
      development process. Other merits include the possibility of hierarchical
      modeling and the use of informative priors, which would lead to a more
      comprehensive utilization of information from both historical and longitudinal
      data. From fixed to adaptive design, we focus on Bayesian randomized controlled
      clinical trials and make extensive comparisons with frequentist counterparts
      through numerical studies.

PMID- 28455233
TI  - Example-based illustrations of design, conduct, analysis and result
      interpretation of multi-regional clinical trials.
AB  - Extensive research has been conducted in the Multi-Regional Clinical Trial (MRCT)
      area. To effectively apply an appropriate approach to a MRCT, we need to
      synthesize and understand the features of different approaches. In this paper,
      examples are used to illustrate considerations regarding design, conduct,
      analysis and interpretation of result of MRCTs. We start with a brief discussion
      of region definitions and the scenarios where different regions have differing
      requirements for a MRCT. We then compare different designs and models as well as
      the corresponding interpretation of the results. We highlight the importance of
      paying special attention to trial monitoring and conduct to prevent potential
      issues associated with the final trial results. Besides evaluating the overall
      treatment effect for the entire MRCT, we also consider other key analyses
      including quantification of regional treatment effects within a MRCT, and
      assessment of consistency of these regional treatment effects.

PMID- 28455234
TI  - Optimal adaptive group sequential design with flexible timing of sample size
      determination.
AB  - Flexible sample size designs, including group sequential and sample size re
      estimation designs, have been used as alternatives to fixed sample size designs
      to achieve more robust statistical power and better trial efficiency. In this
      work, a new representation of sample size re-estimation design suggested by Cui
      et al. [5,6] is introduced as an adaptive group sequential design with flexible
      timing of sample size determination. This generalized adaptive group sequential
      design allows one time sample size determination either before the start of or in
      the mid-course of a clinical study. The new approach leads to possible design
      optimization on an expanded space of design parameters. Its equivalence to sample
      size re-estimation design proposed by Cui et al. provides further insight on re
      estimation design and helps to address common confusions and misunderstanding.
      Issues in designing flexible sample size trial, including design objective,
      performance evaluation and implementation are touched upon with an example to
      illustrate.

PMID- 28455235
TI  - Computational prediction and analysis of deleterious cancer associated missense
      mutations in DYNC1H1.
AB  - Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene encodes a subunit of human
      cytoplasmic dynein complex, which has several crucial functions in the cell, such
      as intracellular transport of DNA damage proteins and mitotic spindle
      positioning. Recent studies reported the altered expression of DYNC1H1 in
      different cancers and DYNC1H1 was suggested to be potential biomarker in
      colorectal cancers. Previously, DYNC1H1 mutations have been associated with
      neurodegenerative diseases, however mutations of DYNC1H1 have not been fully
      investigated in cancers except for different types of pancreatic cancers. In this
      study we aimed to identify the cancer related mutations in DYNC1H1, which are
      deleterious for the DYNC1H1 structure and/or function. We investigated 523 cancer
      related missense mutations in DYNC1H1, which were collected from COSMIC database,
      to predict the effect of mutations on DYNC1H1 function. Of the 523 mutations, we
      identified 28 amino acid substitutions, which were predicted to be deleterious by
      PredictSNP1.0. When we searched for the effect of 28 deleterious mutations on
      protein stability by MUpro and I-Mutant2.0, we observed that most of the
      mutations decrease the protein stability. We analyzed the localization of
      deleterious mutations on primary protein structure and identified that predicted
      deleterious mutations were mainly located in the motor domain, which is crucial
      for the DYNC1H1 function. In addition, we detected close positioning of mutated
      residues in AAA + regions on 3D structure by STRUM and UCSF Chimera. When we
      searched the mutations in COSMIC database, we observed the occurrence of the
      mutations in different cancers, which might show the importance of these regions
      in corresponding cancers. Therefore, our findings provide potential structural
      and functional mutations and hotspots for DYNC1H1.

PMID- 28455236
TI  - Genomics and epigenetics of sexual commitment in Plasmodium.
AB  - Malaria is the disease caused by the apicomplexan parasites belonging to the
      genus Plasmodium. Expanding our arsenal to include transmission-blocking agents
      in our fight against malaria is becoming increasingly important. Such an
      implementation requires detailed understanding of the biology of the Plasmodium
      life cycle stages that are transmissible. Plasmodium gametocytes are the only
      parasite stage that can be transmitted to the mosquito vector and are the product
      of sexual development in a small percentage of parasites that continually
      proliferate in host blood. The critical decision made by asexual erythrocytic
      stages to cease further proliferation and differentiate into gametocytes, as well
      as the first steps they take into maturity, have long remained unknown. Recent
      studies have contributed to a breakthrough in our understanding of this branch
      point in development. In this review, we will discuss the findings that have
      allowed us to make this major leap forward in our knowledge of sexual commitment
      in Plasmodium. We will further propose a model for the mechanism triggering the
      switch to sexual development, constructed around the proteins currently known to
      regulate this process. Further insight into sexual commitment and gametocyte
      development will help identify targets for the development of transmission
      blocking malaria therapies.

PMID- 28455237
TI  - Lungworms and gastrointestinal parasites of domestic cats: a European
      perspective.
AB  - With the exception of Aelurostrongylus abstrusus, feline lungworms have been
      poorly studied. Information on their distribution is patchy and mostly limited to
      case reports. In this study, the occurrence of feline lungworms and co-infecting
      gastrointestinal parasites has been investigated in 12 European countries (i.e.
      Austria, Belgium, Bulgaria, France, Greece, Hungary, Italy, Portugal, Romania,
      Spain, Switzerland and the United Kingdom). An average of 10 domestic cats, with
      regular outdoor access, was sampled each month for 12months, and freshly passed
      faeces were collected. Stools were processed using a McMaster assay and a
      quantitative Baermann-Wetzel method. Animals positive for lungworms and/or
      gastrointestinal parasites were treated with a formulation containing fipronil,
      (S)-methoprene, eprinomectin, and praziquantel (Broadline(r), Merial), and re
      sampled 28days post-treatment. The association between lungworm infection and
      risk factors was analysed using statistical medians/means and the efficacy of the
      treatment against each lungworm species was assessed. Of 1990 cats sampled, 613
      (30.8%) were positive for at least one parasite, while 210 (10.6%) were infected
      by lungworms. The prevalence of lungworm infection varied between the sampled
      sites, with the highest recorded in Bulgaria (35.8%) and the lowest in
      Switzerland (0.8%). None of the cats from Austria or the United Kingdom were
      infected by lungworms. Aelurostrongylus abstrusus was the species most frequently
      detected (78.1%), followed by Troglostrongylus brevior (19.5%), Eucoleus
      aerophilus (14.8%) and Oslerus rostratus (3.8%). The overall efficacy of the
      treatment was 99% for A. abstrusus and 100% for T. brevior, O. rostratus and E.
      aerophilus. Data presented provide a comprehensive account of the diagnosis,
      epidemiology and treatment of feline lungworms in Europe, as well as of the
      occurrence of co-infections by gastrointestinal parasites.

PMID- 28455238
TI  - A novel ex vivo immunoproteomic approach characterising Fasciola hepatica
      tegumental antigens identified using immune antibody from resistant sheep.
AB  - A more thorough understanding of the immunological interactions between Fasciola
      spp. and their hosts is required if we are to develop new immunotherapies to
      control fasciolosis. Deeper knowledge of the antigens that are the target of the
      acquired immune responses of definitive hosts against both Fasciola hepatica and
      Fasciola gigantica will potentially identify candidate vaccine antigens.
      Indonesian Thin Tail sheep express a high level of acquired immunity to infection
      by F. gigantica within 4weeks of infection and antibodies in Indonesian Thin Tail
      sera can promote antibody-dependent cell-mediated cytotoxicity against the
      surface tegument of juvenile F. gigantica in vitro. Given the high protein
      sequence similarity between F. hepatica and F. gigantica, we hypothesised that
      antibody from F. gigantica-infected sheep could be used to identify the
      orthologous proteins in the tegument of F. hepatica. Purified IgG from the sera
      of F. gigantica-infected Indonesian Thin Tail sheep collected pre-infection and
      4weeks p.i. were incubated with live adult F. hepatica ex vivo and the
      immunosloughate (immunoprecipitate) formed was isolated and analysed via liquid
      chromatography-electrospray ionisation-tandem mass spectrometry to identify
      proteins involved in the immune response. A total of 38 proteins were identified
      at a significantly higher abundance in the immunosloughate using week 4 IgG,
      including eight predicted membrane proteins, 20 secreted proteins, nine proteins
      predicted to be associated with either the lysosomes, the cytoplasm or the
      cytoskeleton and one protein with an unknown cellular localization. Three of the
      membrane proteins are transporters including a multidrug resistance protein, an
      amino acid permease and a glucose transporter. Interestingly, a total of 21 of
      the 38 proteins matched with proteins recently reported to be associated with the
      proposed small exosome-like extracellular vesicles of adult F. hepatica,
      suggesting that the Indonesian Thin Tail week 4 IgG is either recognising
      individual proteins released from extracellular vesicles or is
      immunoprecipitating intact exosome-like extracellular vesicles. Five
      extracellular vesicle membrane proteins were identified including two proteins
      predicted to be associated with vesicle transport/ exocytosis (VPS4, vacuolar
      protein sorting-associated protein 4b and the Niemann-Pick C1 protein). RNAseq
      analysis of the developmental transcription of the 38 immunosloughate proteins
      showed that the sequences are expressed over a wide abundance range with 21/38
      transcripts expressed at a relatively high level from metacercariae to the adult
      life cycle stage. A notable feature of the immunosloughates was the absence of
      cytosolic proteins which have been reported to be secreted markers for damage to
      adult flukes incubated in vitro, suggesting that the proteins observed are not
      inadvertent contaminants leaking from damaged flukes ex vivo. The identification
      of tegument protein antigens shared between F. gigantica and F. hepatica is
      beneficial in terms of the possible development of a dual purpose vaccine
      effective against both fluke species.

PMID- 28455239
TI  - Minimally invasive microbiopsies: a novel sampling method for identifying
      asymptomatic, potentially infectious carriers of Leishmania donovani.
AB  - Visceral leishmaniasis (VL) is a potentially lethal, sand fly-borne disease
      caused by protozoan parasites belonging to the Leishmania donovani species
      complex. There are several adequate methods for diagnosing VL, but the majority
      of infected individuals remain asymptomatic, comprising potential parasite
      reservoirs for transmission of the disease. The gold standard for assessing host
      infectiousness to biting vector insects is xenodiagnosis (i.e. scoring infection
      rates among insectary-reared insects that had fed on humans suspected of being
      infected). However, when it comes to sand flies and leishmaniasis, xenodiagnosis
      is an intricate operation burdened by logistical hurdles and ethical concerns
      that prevent its effective application for mass screening of widely dispersed
      communities, particularly in rural regions of underdeveloped countries. Minimally
      invasive microbiopsy (MB) devices were designed to penetrate the skin to a depth
      of ~200um and absorb blood as well as skin cell lysates, mimicking the mode by
      which phlebotomine sand flies acquire blood meals, as well as their composition.
      MBs taken from 137 of 262 volunteers, living in endemic VL foci in Ethiopia,
      detected Leishmania parasites that could potentially be imbibed by feeding sand
      flies. Although the volume of MBs was 10-fold smaller than finger-prick blood
      samples, Leishmania DNA detection rates from MBs were significantly higher,
      implying that skin, more often than blood, was the source of parasites.
      Volunteers with histories of VL were almost as likely as healthy volunteers to
      test positive by MBs (southern Ethiopian focus: 95% CI: 0.35-2.59, P=1.0.
      northern Ethiopian focus 0.87: 95% CI: 0.22-3.76, P=1), suggesting the importance
      of asymptomatic patients as reservoirs of L. donovani. Minimally invasive,
      painless MBs should be considered for reliably and efficiently evaluating both L.
      donovani infection rates among large numbers of asymptomatic carriers and their
      infectiousness to blood-feeding sand flies.

PMID- 28455240
TI  - Hepatitis B virus PreS1 facilitates hepatocellular carcinoma development by
      promoting appearance and self-renewal of liver cancer stem cells.
AB  - Hepatitis B virus (HBV) is a major etiologic agent of hepatocellular carcinoma
      (HCC). However, the molecular mechanism by which HBV infection contributes to HCC
      development is not fully understood. Here, we initially showed that HBV
      stimulates the production of cancer stem cells (CSCs)-related markers (CD133,
      CD117 and CD90) and CSCs-related genes (Klf4, Sox2, Nanog, c-Myc and Oct4) and
      facilitates the self-renewal of CSCs in human hepatoma cells. Cellular and
      clinical studies revealed that HBV facilitates hepatoma cell growth and
      migration, enhances white blood cell (WBC) production in the sera of patients,
      stimulates CD133 and CD117 expression in HCC tissues, and promotes the CSCs
      generation of human hepatoma cells and clinical cancer tissues. Detailed studies
      revealed that PreS1 protein of HBV is required for HBV-mediated CSCs generation.
      PreS1 activates CD133, CD117 and CD90 expression in normal hepatocyte derived
      cell line (L02) and human hepatoma cell line (HepG2 and Huh-7); facilitates L02
      cells migration, growth and sphere formation; and finally enhances the abilities
      of L02 cells and HepG2 cells to induce tumorigeneses in nude mice. Thus, PreS1
      acts as a new oncoprotein to play a key role in the appearance and self-renewal
      of CSCs during HCC development.

PMID- 28455241
TI  - In vitro and in vivo anti-uveal melanoma activity of JSL-1, a novel HDAC
      inhibitor.
AB  - Uveal melanoma (UM) is the most common intraocular malignant neoplasm in adults.
      Despite the availability of enucleation, radiation and chemotherapy, the
      prognosis of patients with metastasis remains poor. Therefore, novel effective
      therapies for patients with metastatic UM are urgently needed. In the present
      study, we demonstrated that JSL-1, a novel HDAC inhibitor, effectively inhibited
      the proliferation. JSL-1 induced apoptosis with increased expression of
      proapoptotic BH3-only protein BIM in UM cells. JSL-1 suppressed migration and
      invasion of UM cells with MMP-2 decreased. Furthermore, JSL-1 blocked the
      canonical Wnt/beta-catenin pathway, impaired self-renewal capacity and decreased
      percentage of ALDH+ cells, thereby reflecting elimination of UM cancer stem-like
      cells (CSCs) which are believed seeds of metastasis. Importantly, JSL-1 potently
      inhibited the growth of uveal melanoma xenograft in NOD-SCID mice. These results
      suggested that JSL-1 may be a promising therapeutic agent for UM.

PMID- 28455242
TI  - The role of the NORE1A tumor suppressor in Oncogene-Induced Senescence.
AB  - The Ras genes are the most frequently mutated oncogenes in human cancer. However,
      Ras biology is quite complex. While Ras promotes tumorigenesis by regulating
      numerous growth promoting pathways, activated Ras can paradoxically also lead to
      cell cycle arrest, death, and Oncogene-Induced Senescence (OIS). OIS is thought
      to be a critical pathway that serves to protect cells against aberrant Ras
      signaling. Multiple reports have highlighted the importance of the p53 and Rb
      tumor suppressors in Ras mediated OIS. However, until recently, the molecular
      mechanisms connecting Ras to these proteins remained unknown. The RASSF family of
      tumor suppressors has recently been identified as direct effectors of Ras. One of
      these members, NORE1A (RASSF5), may be the missing link between Ras-induced
      senescence and the regulation of p53 and Rb. This occurs both quantitatively, by
      promoting protein stability, as well as qualitatively via promoting critical pro
      senescent post-translational modifications. Here we review the mechanisms by
      which NORE1A can activate OIS as a barrier against Ras-mediated transformation,
      and how this could lead to improved therapeutic strategies against cancers having
      lost NORE1A expression.

PMID- 28455243
TI  - The second-generation ALK inhibitor alectinib effectively induces apoptosis in
      human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic
      neuroblastoma mouse model.
AB  - Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most
      cases of hereditary neuroblastoma (NB) and the constitutively active kinase
      activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK
      kinase is a potential therapeutic target for NB. In this study, we show that the
      novel ALK inhibitor alectinib effectively suppressed cell proliferation and
      induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK
      (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling. In
      addition, alectinib enhanced doxorubicin-induced cytotoxicity and apoptosis in NB
      cells. Furthermore, alectinib induced apoptosis in an orthotopic xenograft NB
      mouse model. Also, in the TH-MYCN transgenic mouse model, alectinib resulted in
      decreased tumor growth and prolonged survival time. These results indicate that
      alectinib may be a promising therapeutic agent for the treatment of NB.

PMID- 28455245
TI  - RCCD1 depletion attenuates TGF-beta-induced EMT and cell migration by stabilizing
      cytoskeletal microtubules in NSCLC cells.
AB  - Lung cancer is one of the most lethal cancers due to its highly metastatic
      spreading. The motility of lung cancer cells is regulated by paracrine factors,
      such as TGF-beta, in the tumor microenvironment through the induction of
      epithelial-to-mesenchymal transition (EMT). The stability of microtubules is
      reported to be associated with the EMT process and the migration of cancer cells.
      Here, we observed that RCC1 domain-containing protein 1 (RCCD1) is highly
      expressed in non-small cell lung cancer (NSCLC) patients with poor prognosis, and
      RCCD1 is much higher expressed in tumor tissues compared with adjacent normal
      tissues. Depletion of RCCD1 using siRNAs significantly inhibits the migration of
      lung cancer cells. Subsequent studies reveal that the loss of RCCD1 results in
      upregulation of acetylated alpha-tubulin levels and stabilizes cytoskeletal
      microtubules. Mechanistically, we observed that RCCD1 modulates the stability of
      microtubules through interacting with JMJD5. Furthermore, RCCD1 depletion
      significantly attenuates the TGF-beta-induced EMT process, as assessed by altered
      expression of epithelial and mesenchymal markers (Occludin, Vimentin and Snail),
      and inhibits TGF-beta-induced cell migration. Collectively, these findings
      support RCCD1 as a novel regulator of TGF-beta-induced EMT in NSCLC.

PMID- 28455244
TI  - GOT1-mediated anaplerotic glutamine metabolism regulates chronic acidosis stress
      in pancreatic cancer cells.
AB  - The increased rate of glycolysis and reduced oxidative metabolism are the
      principal biochemical phenotypes observed in pancreatic ductal adenocarcinoma
      (PDAC) that lead to the development of an acidic tumor microenvironment. The pH
      of most epithelial cell-derived tumors is reported to be lower than that of
      plasma. However, little is known regarding the physiology and metabolism of
      cancer cells enduring chronic acidosis. Here, we cultured PDAC cells in chronic
      acidosis (pH 6.9-7.0) and observed that cells cultured in low pH had reduced
      clonogenic capacity. However, our physiological and metabolomics analysis showed
      that cells in low pH deviate from glycolytic metabolism and rely more on
      oxidative metabolism. The increased expression of the transaminase enzyme GOT1
      fuels oxidative metabolism of cells cultured in low pH by enhancing the non
      canonical glutamine metabolic pathway. Survival in low pH is reduced upon
      depletion of GOT1 due to increased intracellular ROS levels. Thus, GOT1 plays an
      important role in energy metabolism and ROS balance in chronic acidosis stress.
      Our studies suggest that targeting anaplerotic glutamine metabolism may serve as
      an important therapeutic target in PDAC.

PMID- 28455246
TI  - Fn14.TRAIL fusion protein is oligomerized by TWEAK into a superefficient TRAIL
      analog.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates
      specific anti-cancer activity, but insufficient efficacy in patients. A fusion
      protein Fn14.TRAIL, that combines soluble TRAIL molecule with a specific TWEAK
      receptor Fn14, is a better apoptosis-inducer for hepatocellular carcinomas than
      soluble TRAIL. However, Fn14.TRAIL does not effectively induce apoptosis in
      tumors of the lymphoid origin. As malignant cell apoptosis is strongly enhanced
      by secondary oligomerization of TRAIL, we tested the hypothesis that soluble
      Fn14.TRAIL can be oligomerized and become more active by adding TWEAK, a cytokine
      secreted in the tumor environment. We revealed that TWEAK and Fn14.TRAIL
      spontaneously formed a stable complex that induced apoptosis of malignant
      lymphoblasts earlier and more efficiently than TRAIL. The TWEAK-modified
      Fn14.TRAIL oligomer bound to target cells and delivered apoptotic signaling via
      TRAIL receptors. The oligomer induced faster and stronger cleavage of procaspase
      8, -9, and -3; BID; poly-ADP ribose polymerase; and RIP compared to TRAIL. The
      oligomer also reduced expression of the anti-apoptotic proteins c-FLIP short and
      cIAP-1. Our data indicate that Fn14.TRAIL can be converted into a highly
      effective TRAIL oligomer upon binding to TWEAK.

PMID- 28455247
TI  - RE: Cancer incidence and mortality in China, 2013 by Chen et al.

PMID- 28455248
TI  - Placebo Analgesia From a Rubber Hand.
AB  - : Placebo analgesia, reductions in pain after administration of an inert
      treatment, is a well documented phenomenon. We report, to our knowledge, the
      first demonstration that placebo analgesia can be experienced when a sham
      analgesic is applied onto a rubber hand. The effect was obtained by exploiting
      the rubber hand illusion, in which ownership is felt over a rubber arm that is
      unattached to the body. Under conditions of synchronous as well as asynchronous
      visuotactile stimulation, a thermal pain stimulus was delivered on the real arm
      of 20 participants and seemingly also on the rubber arm, before and after
      applying a sham analgesic and a control cream only to the rubber arm. During
      synchronous visuotactile stimulation, pain was experienced on the rubber arm, and
      the application of the sham analgesic to the rubber arm significantly decreased
      the severity of reported pain. This shows that experience of the body can
      modulate expectations and the induction of placebo analgesia. PERSPECTIVE: This
      article presents an experiment suggesting that a placebo treatment applied to a
      rubber hand during the rubber hand illusion can produce placebo analgesia. This
      finding indicates that embodiment may influence the placebo effect, a previously
      unexamined factor in the treatment process with potential applications to
      treatment administration.

PMID- 28455249
TI  - Predictors of Treatment Outcome in Contextual Cognitive and Behavioral Therapies
      for Chronic Pain: A Systematic Review.
AB  - : There is increasing evidence that contextual forms of cognitive-behavioral
      therapy (CBT) are effective in the management of chronic pain, yet little is
      understood about the factors that moderate or predict outcomes in these
      treatments. This systematic review aimed to identify pretreatment participant
      characteristics associated with positive treatment responses in contextual CBT
      for chronic pain. Medline, EMBASE, PsychINFO, and CENTRAL were searched to
      identify eligible studies. Studies were included if the participants were adults
      with chronic pain, designs were longitudinal, treatments focused on psychological
      flexibility or mindfulness, and reported results allowed for examination of
      moderators or predictors of standard treatment outcomes. Of 991 records initially
      identified, 20 were eligible for inclusion in the review. Some evidence suggested
      that baseline emotional functioning predicts treatment response, but the
      direction of this association varied between studies. Substantive findings were
      inconsistent and inconclusive, however, methodological limitations were
      consistent. These included treatment heterogeneity, and a lack of theoretical, a
      priori guidance in examining potential predictors. Future research should adopt a
      theoretically based approach to examining moderators in relation to specific
      treatment methods and therapeutic processes. Considering moderation without first
      considering mediation is probably a limited strategy. PERSPECTIVE: In this
      systematic review we examined evidence for potential predictors or moderators of
      outcomes in contextual CBT for chronic pain. Substantive findings were
      inconclusive but important methodological limitations and a lack of theoretical
      guidance were found. Future research should explicitly plan relevant methods and
      follow clear theoretical models.

PMID- 28455250
TI  - A Longitudinal Randomized Trial of the Effect of Consistent Pain Management for
      Infant Vaccinations on Future Vaccination Distress.
AB  - : The objective was to determine if consistent pain management during vaccine
      injections has a beneficial effect on future infant pain reactivity. This was a
      multicenter, longitudinal, double-blind, double-dummy, add-on, randomized
      controlled trial. Healthy infants were randomized to 1 of 4 add-on pain
      management regimens for all vaccinations in the first year of life: 1) placebo
      control (standard care), 2) parent video education about infant soothing (video),
      3) video and oral sucrose solution (sucrose), 4) video and sucrose and topical
      liposomal lidocaine (lidocaine). At 15-month vaccinations, all active pain
      interventions were administered (video and sucrose and lidocaine); however,
      individuals remained blinded to the original treatments given. Pain at 15 months
      was evaluated during 3 procedure phases (baseline, needle injection, and
      recovery) by a researcher unaware of group allocation using a validated measure,
      the Modified Behavioural Pain Scale (range, 0-10). Altogether, 352 infants
      participated; characteristics did not differ among groups (P > .05). Pain scores
      did not differ among groups during baseline (P = .642), needle injection (P =
      .739), or recovery (P = .750) phases. In conclusion, there was no evidence of a
      long-term benefit of consistent use of pain interventions in the first year of
      life on future infant pain responsivity at 15-month vaccinations. PERSPECTIVE:
      This randomized controlled trial did not find a long-term benefit of consistent
      pain management during infant vaccinations on future infant pain responsivity at
      15 months. The results are relevant to clinicians and researchers studying and
      evaluating pain interventions in children undergoing medical procedures.

PMID- 28455251
TI  - Triphasic Dynamic Contrast-Enhanced Computed Tomography in the Differentiation of
      Benign and Malignant Gallbladder Polypoid Lesions.
AB  - BACKGROUND: With triphasic, dynamic contrast-enhanced CT scan to identify benign
      and malignant gallbladder polypoid lesions, we hope to determine an accurate
      diagnosis before surgery. STUDY DESIGN: Ninety patients with gallbladder polypoid
      lesions were treated surgically in the Department of Hepatobiliary Surgery, the
      First Affiliated Hospital of China Medical University, Shenyang, China, from July
      2013 to July 2016, and divided into 2 groups according to postoperative
      pathologic results: a malignant group with 44 patients and a benign group with 46
      patients. Triphasic, dynamic contrast-enhanced CT scan was performed in 90
      patients within 2 weeks before surgery. The CT image parameters were measured and
      analyzed by 2 senior radiologists and a hepatobiliary surgeon in blind. RESULTS:
      Mean age of the malignant group was significantly older than that of the benign
      lesion group (p < 0.01). With the CT image parameters, the maximal diameter of
      the lesion was significantly longer in malignant lesions than in benign lesions
      (p < 0.01). There was a significant difference in plain CT, delayed phase CT, and
      DeltaCT values (DeltaCT = portal venous phase CT value minus delayed phase CT
      value) between the 2 groups (all p < 0.01). In terms of differentiating malignant
      and benign gallbladder polypoid lesions, the DeltaCT value was superior to that
      of plain and delayed phase CT in both sensitivity and specificity (p < 0.05).
      CONCLUSIONS: In triphasic, dynamic contrast-enhanced CT scan, plain CT value,
      delayed phase CT value, and DeltaCT value could detect malignant lesions of
      gallbladder polyps, with the highest sensitivity and specificity of DeltaCT.

PMID- 28455252
TI  - Fabrication of an ultrafine fish gelatin nanofibrous web from an aqueous solution
      by electrospinning.
AB  - Electrospinning of aqueous gelatin solution obtained from bovine or porcine
      sources has been difficult to achieve without additional facilities, such as a
      temperature control oven or heating cover. Gelatin from cold-water fish has low
      contents of proline (Pro) and hydroxyproline (Hyp) compared with mammalian
      derived gelatin. For this reason, the fish-derived gelatin maintains a sol state
      without showing gelation behavior at room temperature. In the present study, we
      prepared an ultrafine fish gelatin nanofibrous web by electrospinning from
      aqueous solutions without any additive polymers or temperature control
      facilities. The concentration and viscosity of fish gelatin are the most
      important factor in determining the electrospinnability and fiber diameter.
      Electrospinning of aqueous fish gelatin has the highest nanofiber productivity
      compared to other organic solvent systems. Using glutaraldehyde vapor (GTA), the
      water stability was improved and substantial enhancement was achieved in the
      mechanical properties. Finally, the cytotoxicity of a fish gelatin nanofibrous
      scaffold was evaluated based on a cell proliferation study by culturing human
      dermal fibroblasts (HDFs) compared with a fish gelatin film and nanofibrous mat
      from mammalian gelatin. The result shows better initial cell attachment and
      proliferation compared with the fish gelatin film and no significant difference
      compared with mammalian-derived gelatin nanofibrous mat. We expect that
      electrospinning of aqueous fish gelatin could be an effective alternative
      mammalian gelatin source.

PMID- 28455253
TI  - Thermal and dynamic mechanical properties of cellulose nanofibers reinforced
      epoxy composites.
AB  - The current study presents about the effect of cellulose nanofibers (CNFs) filler
      on the thermal and dynamic mechanical analysis (DMA) of epoxy composites as a
      function of temperature. In this study hand lay-up method was used to fabricate
      CNF reinforced Epoxy nanocomposites with CNF loading of 0.5%, 0.75%, and 1% into
      epoxy resin. The obtained thermal and DMA results illustrates that thermal
      stability, char content, storage modulus (E'), loss modulus (E") and glass
      transition temperature (Tg) increases for all CNF/epoxy nanocomposites compared
      to the pure epoxy. Thermal results revealed that 0.75% offers superior resistance
      or stability towards heat compared to its counterparts. In addition, 0.75%
      CNF/epoxy nanocomposites confers highest value of storage modulus as compared to
      0.5% and 1% filler loading. Hence, it is concluded that 0.75% CNFs loading is the
      minimal to enhance both thermal and dynamic mechanical properties of the epoxy
      composites and can be utilized for advance material applications where thermal
      stability along with renewability are prime requirements.

PMID- 28455254
TI  - Effects of Chrysanthemum indicum polysaccharide and its phosphate on anti-duck
      hepatitis a virus and alleviating hepatic injury.
AB  - To explore new effective anti-duck hepatitis A virus drugs, Chrysanthemum indicum
      polysaccharide (CIPS) was phosphorylation modified using STMP-STPP method, and
      phosphorylated Chrysanthemum indicum polysaccharide (pCIPS) was obtained.
      Characteristic absorption peaks were observed in pCIPS using IR spectrum,
      suggested that CIPS was successfully modified. In addition, field emission
      scanning electron micro-scope (FE-SEM) was used to observe the polysaccharides'
      surface features. In vitro, we found that the survival rate of DHAV-infected
      hepatocytes increased after the two drugs treatment, indicated that the two drugs
      possess good anti-DHAV activity. The results of real-time PCR showed that pCIPS
      inhibited the virus gene replication more effectively than CIPS. Reed-Muench
      assay was used to observe the changes of the virulence, and the expression level
      of IFN-beta was observed to verify the changes of virulence. In vivo experiment,
      the blood virus content reduced after CIPS and pCIPS treatment. To evaluate the
      ducklings' hepatic injury, the serum ALT, AST, TP and ALB levels were detected.
      Results showed that both CIPS and pCIPS could alleviate the hepatic injury of
      ducklings infected DHAV, especially for pCIPS. All the results above mentioned
      demonstrated that the anti-DHAV activity of CIPS was enhanced after
      phosphorylation modification.

PMID- 28455255
TI  - A novel laccase from white rot fungus Trametes orientalis: Purification,
      characterization, and application.
AB  - A novel laccase (Tolacc-T) from white rot fungus Trametes orientalis was enriched
      to apparent homogeneity with a specific activity of 20.667U/mg protein and
      recovery yield of 47.33%. The SDS-PAGE gave a single band indicating that Tolacc
      T appears as a monomeric protein with a molecular mass of 44.0kDa. Domain
      structure analysis revealed that Tolacc-T contained a typical copper II binding
      domain and shared three potential N-glycosylation sites, but had no copper I
      binding domain, demonstrating that the enzyme is really a laccase, but a novel
      laccase. Optimal pH and temperature of Tolacc-T was 4.0 and 80 degrees C,
      respectively, and it retained more than 80% of its original activity after 2h
      incubation at 10 degrees C to 50 degrees C. The enzyme exhibited strict substrate
      specificity towards ABTS but showed no or trace activities towards other
      substrates. Among the metals tested, Mn2+ was proved to be the best activator for
      enhancing the laccase activity. A strongly inhibiting effect was found when NaN3,
      L-cysteine, and DTT were added to the enzyme. However, Tolacc-T activity was
      little bit inhibited in the presence of chelator EDTA. Furthermore, the enzyme
      was capable of degrading structurally different synthetic dyes in the absence of
      a redox mediator.

PMID- 28455256
TI  - alpha-Glucosidase inhibition by prenylated and lavandulyl compounds from Sophora
      flavescens roots and in silico analysis.
AB  - The enzyme alpha-glucosidase is a good drug target for the treatment of diabetes
      mellitus. Four minor flavonoids (1-4) from roots of Sophora flavescens showed the
      inhibitory activity, with IC50 values ranging from 11.0+/-0.3 to 50.6+/-1.3MUM,
      toward alpha-glucosidase. An enzyme kinetics analysis of them revealed that the
      compounds 1 and 4 were non-competitive, and compounds 2 and 3 were un-competitive
      inhibitors. For molecular docking, 3-dimensional structure of alpha-glucosidase
      was built by homology modeling. As the result, four compounds 1-4 were confirmed
      to interact into common binding site of alpha-glucosidase. In addition, all of
      the four prenylated and lavandulyl compounds (1-4) were abundant in an ethyl
      acetate fraction separated from a methanol extract, and the potential inhibitor
      (3) was extracted best using tetrahydrofuran.

PMID- 28455257
TI  - Molecular insights into the inhibitory mechanism of rifamycin SV against beta2
      microglobulin aggregation: A molecular dynamics simulation study.
AB  - Dialysis-related amyloidosis (DRA) is a severe condition characterized by the
      accumulation of amyloidogenic beta2-microglobulin (beta2m) protein around
      skeletal joints and bones. The small molecules that modulate beta2m aggregation
      have been identified in vitro, however, the underlying inhibitory mechanism
      remain elusive. In the present study, molecular docking and molecular dynamics
      (MD) simulations were performed to elucidate the inhibitory mechanism of an
      antibiotic, rifamycin SV (C1) reported for its in vitro anti-aggregation activity
      against beta2m. The molecular docking analysis highlight that C1 display
      hydrophobic contacts with residues in the aggregation prone region of beta2m. MD
      simulations reveal enhanced structural stability of beta2m in the presence of C1.
      C1 inhibit the conformational transition of the C-terminal region of beta2m from
      a beta-sheet to random coil conformation, which is reported for the initiation of
      fibrillogenesis of beta2m. The results of the present study provide insight into
      the key interactions and underlying inhibitory mechanism of a small molecule
      against beta2m aggregation that will help in the design and development of more
      potent, novel inhibitors of beta2m aggregation.

PMID- 28455258
TI  - Protective effect of pilose antler peptide on cerebral ischemia/reperfusion (I/R)
      injury through Nrf-2/OH-1/NF-kappaB pathway.
AB  - The purpose of the current study was to detect the effect of pilose antler
      peptide (PAP) on cerebral ischemia and explore its potential mechanism. Middle
      cerebral artery occlusion (MCAO) was performed to investigate the effects of PAP
      on cerebral ischemia. The rats were randomly divided into five groups: sham
      group, model(I/R) group, I/R+Clopidogrel group, I/R+PAP (50mg/kg) group, I/R+PAP
      (100mg/kg) group. The results showed that PAP significantly reduced brain infarct
      size, inhibited cerebral edema, decreased th eneurological deficits. Treatment
      with PA reduced the contents of malondialdehyde(MDA) and restore the activity of
      superoxide dismutase(SOD) in serum and brains. Lig also could effectively
      decrease the levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and
      tumor necrosis factor-alpha (TNF-alpha) in serum and brain tissues of the MCAO
      rats. Western blot results demonstrated that PAP up-regulated the expressions of
      Nrf-2 and HO-1, also blocked the phosphorylations of IkappaB kinases(IKK)alpha,
      IKKbeta, inhibitor of NF-kappaB(IkappaB)alpha, nuclear factor kappa B(NF-kappaB)
      p65 in I/R-induced brains. Our findings suggested that PAP effectively attenuated
      the I/R-induced cerebral ischemia through Nrf-2/HO-1/NF-kappaB pathway.

PMID- 28455259
TI  - The effect of social norms messaging regarding skin carotenoid concentrations
      among college students.
AB  - Descriptive social-normative messaging positively influences short-term dietary
      choices and healthy food intake. The purpose of this study was to evaluate the
      effects of descriptive normative messages on college students' skin carotenoid
      concentrations (a biomarker of carotenoid-containing fruit and vegetable [FV]
      intake) over an 8-week period. 251 college students consented to participate and
      74% completed the study. Students were randomly assigned to groups who, following
      a baseline evaluation of skin-carotenoid levels, were told how their score ranked
      within a peer group of college students attending the same university
      (Individualized Normative group), that their score was in the lower 20th
      percentile of the peer group (Manipulated Normative group), or were given no
      information about their score or the peer group (Control group). Skin carotenoid
      concentrations were reassessed 8 weeks after the normative messages were
      presented or withheld. Skin carotenoid levels of those in the Manipulated
      Normative group increased significantly more than did scores of those in the
      Control group (t (126) = 3.74, p < 0.001; d = 0.67), but these students' self
      reported FV intake did not increase. This finding suggests normative messaging
      can influence behavior for up to 8 weeks, but future research must better
      evaluate if the increase in skin carotenoids reflects increased FV consumption,
      increased consumption of carotenoid-containing FV (with decreased consumption of
      other FV), or is accounted for by some other behavior change (e.g., increased use
      of supplements). These findings support further exploration of normative
      messaging as a technique for producing the long-term behavior change needed to
      impact public health.

PMID- 28455260
TI  - TAS2R38 and CA6 genetic polymorphisms, frequency of bitter food intake, and blood
      biomarkers among elderly woman.
AB  - OBJECTIVE: Taste sensitivity is one of the most important biological determinants
      of food choice. Three SNPs of the TAS2R38 gene (rs713598, rs1726866, and
      rs10246939) give rise to two common haplotypes: PAV and AVI. These haplotypes, as
      well as an SNP within the CA6 gene (rs2274333) that encodes carbonic anhydrase VI
      (CA6), correlate with bitterness perception. The extent of consumption of bitter
      food may influence some health outcomes. The aim of this study is thus to
      investigate the impact of the TAS2R38 and CA6 genetic polymorphisms on the choice
      of bitter food, BMI, blood lipoprotein, and glucose concentrations as well as
      systemic inflammation in elderly women. METHODS: The associations between the
      TAS2R38 diplotype, CA6 genotype, and the intake of bitter-tasting foods were
      studied in a group of 118 Polish women over 60 years of age. The intake of
      Brassica vegetables, grapefruit, and coffee was assessed using a food frequency
      questionnaire. Biochemical parameters were measured using the spectrophotometric
      method. Genotyping was performed using the high resolution melting method.
      RESULTS: We found a correlation between lipid profile, glucose and CRP levels,
      and frequency of bitter food intake. The AVI/AVI subjects drank coffee more
      frequently than did the PAV/PAV homozygotes, as did the A carriers of CA6 in
      comparison with the GG homozygotes. We also observed that simultaneous carriers
      of the PAV haplotype and A allele of TAS2R38 and CA6, respectively, choose white
      cabbage more frequent and had lower plasma levels of CRP and glucose than did
      AVI/AVI and GG homozygotes. CONCLUSIONS: In elderly women, the TAS2R38 and CA6
      polymorphisms may affect the frequency of consumption of coffee and white
      cabbage, but not of other bitter-tasting foods.

PMID- 28455261
TI  - When hunger does (or doesn't) increase unhealthy and healthy food consumption
      through food wanting: The distinctive role of impulsive approach tendencies
      toward healthy food.
AB  - OBJECTIVE: Hunger indirectly triggers unhealthy high-calorie food consumption
      through its positive effect on the incentive value (or "wanting") for food. Yet,
      not everyone consumes unhealthy food in excess, suggesting that some individuals
      react differently when they are exposed to unhealthy high-calorie food, even when
      they are hungry. The purpose of the present study was to investigate whether
      individual differences in impulsive approach tendencies toward food may explain
      how, and for whom, hunger will influence unhealthy food consumption through its
      effect on food wanting. A complementary goal was to explore whether these
      individual differences also influence healthy food consumption. METHODS: Students
      (N = 70) completed a questionnaire measuring their hunger and food wanting. Then,
      they performed a manikin task designed to evaluate their impulsive approach
      tendencies toward unhealthy food (IAUF) and healthy food (IAHF). The main
      outcomes variables were the amount of sweets (i.e., unhealthy food) and raisins
      (i.e., healthy food) consumed during a product-testing task. RESULTS: A moderated
      mediation analysis revealed that the indirect effect of hunger on unhealthy
      consumption through food wanting was moderated by IAHF. Specifically, hunger
      positively predicted sweets consumption through wanting for food among
      individuals with a low or moderate, but not high IAHF. The moderated mediation
      pattern was, however, not confirmed for IAUF. Finally, results revealed a direct
      and positive effect of IAHF on raisins consumption. CONCLUSION: These findings
      showed that IAHF play a protective role by preventing hunger to indirectly
      increase unhealthy food consumption through wanting for food. It confirms the
      importance of considering how individuals may differ in their impulsive approach
      tendencies toward food to better understand why some individuals will increase
      their unhealthy food intake when they are hungry, whereas other will not.

PMID- 28455262
TI  - Examining the impact of a school-based fruit and vegetable co-op in the Hispanic
      community through documentary photography.
AB  - Hispanic families are at elevated risk for certain diet related illnesses
      including obesity and diabetes. Brighter Bites is a 16-week school-based program
      that delivers produce and nutrition education to high-need areas. The purpose of
      this study was to explore the adoption of Brighter Bites healthy eating
      strategies in low-income Spanish-speaking families as well as barriers to the
      sustainability of improved dietary behaviors using Photovoice. Two researchers
      worked with a predominately Hispanic, low-income public school to conduct the
      project. Spanish speaking parents participating in Brighter Bites were recruited
      and five mothers completed the study. Participants developed research questions,
      took documentary photos, attended group analysis sessions, and organized a
      community event. Photos from participants were gathered at two time points: i)
      during the Brighter Bites produce distributions, and ii) when the distributions
      were no longer in session. Participants organized resulting photos into themes
      during discussion groups that proceeded each photo-taking period. Themes that
      emerged during the produce distribution period included: cost savings, increased
      variety and accessibility of fresh produce, and ability to practice healthy
      eating. Themes that emerged when the weekly produce distributions were no longer
      in session included: increased costs, lack of variety, the continued effect of
      Brighter Bites, and innovative ways to cook with produce. Overall, participants
      were enthusiastic about the benefits they experienced with the program, but noted
      hardships in accessing nutritious food without the produce distributions in
      session. Innovative approaches are needed to create sustainable pathways to
      healthful food access after community nutrition interventions are complete.

PMID- 28455263
TI  - An historical perspective on variety in United States dining based on menus.
AB  - While food variety continues to be of major interest to those studying eating and
      health, research has been mainly limited to laboratory research of simple meals.
      This paper seeks to enlarge the scope of eating research by examining the food
      offered in the earliest menus in United States restaurants and hotels of the
      early and mid-19th c, when restaurants began. This reveals a very large variety
      in what food was offered. The paper discusses why variety has declined in the US
      and probably elsewhere, including changes in the customer, changes in food
      service, changes of food availability, and the industrialization of the food
      supply. Menu analysis offers another approach to studying dietary variety across
      cultures and across time.

PMID- 28455265
TI  - Age and sex in drug development and testing for adults.
AB  - Individualization of drug therapy requires that the right drug be administered at
      the correct dose to patients who are likely to achieve the highest benefit and
      lowest risk. Female sex and age comprise two important risk factors for altered
      drug exposure and response. This review summarizes the current state of science
      for considering age and sex-related factors along the drug development pipeline,
      from cell culture and animal research through all phases of clinical trials in
      humans. A set of recommendations is provided to improve standards for integrating
      age and sex into the study design, analysis, and reporting of pre-clinical and
      clinical assessment of new molecular entities and biologics in adults.

PMID- 28455264
TI  - Using functional and molecular MRI techniques to detect neuroinflammation and
      neuroprotection after traumatic brain injury.
AB  - This study was designed to investigate whether functional and molecular MRI
      techniques are sensitive biomarkers for assessment of neuroinflammation and drug
      efficacy after traumatic brain injury (TBI) in rats. We subjected rats to a
      controlled cortical impact model and used behavioral tests, histology, and
      immunofluorescence to assess whether flavonoid pinocembrin provides cerebral
      protection and improves functional recovery. Most importantly, we used multiple
      noninvasive structural, functional, and molecular MRI techniques to examine
      whether the pinocembrin-related neuroprotection and attenuation of
      neuroinflammation can be detected in vivo. Significant increases in cerebral
      blood flow (CBF) and amide proton transfer-weighted (APTw) MRI signals were
      observed in the perilesional areas in untreated TBI rats at 3days and could be
      attributed to increased glial response. In addition, increased apparent diffusion
      coefficient and decreased magnetization transfer ratio signals in untreated TBI
      rats over time were likely due to edema. Post-treatment with pinocembrin
      decreased microglial/macrophage activation at 3days, consistent with the recovery
      of CBF and APTw MRI signals in regions of secondary injury. These findings
      suggest that pinocembrin provides cerebral protection for TBI and that multiple
      MRI signals, CBF and APTw in particular, are sensitive biomarkers for
      identification and assessment of neuroinflammation and drug efficacy in the TBI
      model.

PMID- 28455266
TI  - Suppression of ABCG2 mediated MDR in vitro and in vivo by a novel inhibitor of
      ABCG2 drug transport.
AB  - Cancer is a disease whose treatment is often limited due to the development of a
      phenomenon known as multidrug resistance (MDR). There is an immense demand for
      development of novel agents that can overcome the MDR in cancer. A group of
      transmembrane proteins called ATP-binding cassette transporters, present
      ubiquitously in the human body possesses a modular architecture, contributing
      immensely towards the development of MDR. An analysis of structural congeners
      among a group of compounds led to the discovery of CCTA-1523 that could
      selectively reverse ABCG2-mediated MDR in cancer cells in vitro and in vivo. CCTA
      1523 (5MUM) sensitized the ABCG2 overexpressing cancer cells and ABCG2
      transfected cells to the substrate chemotherapeutic drugs. The reversal ability
      of CCTA-1523 was primarily due to the inhibition of the efflux function of ABCG2;
      also there was no change in the protein expression or the localization of the
      ABCG2 in the presence of CCTA-1523. The reversal effect of CCTA-1523 was
      reversible. Importantly, co-administration of CCTA-1523 restored the in vivo
      antitumor activity of doxorubicin in ABCG2 overexpressing tumor xenografts. Taken
      together, our findings indicate that CCTA-1523 is a potent, selective and
      reversible modulator of ABCG2 that may offer therapeutic promise for multidrug-
      resistant malignancies.

PMID- 28455267
TI  - Metabotropic glutamate receptor 5 mediates the suppressive effect of 6-OHDA
      induced model of Parkinson's disease on liver cancer.
AB  - Numerous epidemiological studies suggested that there is a variable cancer risk
      in patients with Parkinson's disease (PD). However, the underlying mechanisms
      remain unclear. In the present study, the role of metabotropic glutamate receptor
      5 (mGluR5) has been investigated in 6-hydroxydopamine (6-OHDA)-induced PD
      combined with liver cancer both in vitro and in vivo. We found that PD cellular
      model from 6-OHDA-lesioned MN9D cells suppressed the growth, migration, and
      invasion of Hepa1-6 cells via down-regulation of mGluR5-mediated ERK and Akt
      pathway. The application of 2-methyl-6-(phenylethyl)-pyridine and knockdown of
      mGluR5 further decreased the effect on Hepa-1-6 cells when co-cultured with
      conditioned media. The effect was increased by (S)-3,5-dihydroxyphenylglycine and
      overexpression of mGluR5. Moreover, more release of glutamate from 6-OHDA
      lesioned MN9D cells suppressed mGluR5-mediated effect of Hepa1-6 cells.
      Application of riluzole eliminated the increased glutamate release induced by 6
      OHDA in MN9D cells and aggravated the suppressive effect on Hepa-1-6 cells. In
      addition, the growth of implanted liver cancer was inhibited in 6-OHDA induced PD
      like rats, and was associated with increased glutamate release in the serum and
      down-regulation of mGluR5 in tumor tissue. Collectively, these results indicate
      that selective antagonism of glutamate and mGluR5 has a potentially beneficial
      effect in both liver cancer and PD, and thus may provide more understanding for
      the clinical investigation and further an additional therapeutic target for these
      two diseases.

PMID- 28455268
TI  - NSAID-activated gene 1 and its implications for mucosal integrity and
      intervention beyond NSAIDs.
AB  - In spite of the beneficial actions of non-steroid anti-inflammatory drugs
      (NSAIDs) in epithelial inflammation and cancers, their use is limited because of
      their cyclooxygenase-dependent or independent gastrointestinal toxicity. As an
      eicosanoid-independent mediator, NSAID-activated gene 1 (NAG-1) has been assessed
      for its involvement in cellular integrity and pathogenesis in mucosal
      inflammation and carcinogenesis. At the cellular levels, NAG-1 is involved in the
      cell growth regulation (cell death, cell cycle arrest, or proliferation) in
      epithelial and mesenchymal tissues. Moreover, NAG-1 can modulate inflammatory
      responses in either direct or indirect manner, which ultimately affects
      fibrogenic and tumorigenic processes in various disease states. Finally, NAG-1
      has been assessed for its contribution to cellular behavior, such as the mobility
      of epithelial and malignant cells in response to the external insults or
      oncogenic stimulation in the mucosa. This review on the "Yin-Yang" nature of NAG
      1-mediated responses provides comprehensive insights into therapeutic and
      diagnostic interventions for mucosal health and integrity in the human body.

PMID- 28455269
TI  - Long QT syndrome presents not only as QT prolongation but also as abnormal T-wave
      morphology.

PMID- 28455270
TI  - Assessing the clinical efficacy of quinidine in Brugada syndrome: "Mission:
      Impossible"?

PMID- 28455271
TI  - Evaluation of ablation catheter technology: Comparison between thigh preparation
      model and an in vivo beating heart.
AB  - BACKGROUND: An in vivo animal thigh model is the standard technique for
      evaluation of ablation catheter technologies, including efficacy and safety of
      ablation. However, the biophysics of ablation in a thigh model may not be similar
      to a beating heart. OBJECTIVE: The purpose of this study was to compare efficacy
      and safety of ablation between a thigh preparation model and a beating heart.
      METHODS: In 7 swine, radiofrequency ablation using a 3.5-mm open irrigated
      catheter (ThermoCool Smart Touch) was performed sequentially in a thigh muscle
      and in vivo beating ventricles. Ablation was performed at low (30 W for 40 s) and
      high (40 W for 60 s) energy settings and at similar contact force. Ablation
      lesions were scanned in high resolution and measured using electronic calipers.
      RESULTS: A total of 152 radiofrequency ablation lesions were measured (86 thigh
      and 66 heart). At low energy, lesion width was greater in the thigh model (12.19
      +/- 1.8 mm vs 8.99 +/- 2.1 mm; P <.001), whereas lesion depth was similar between
      the thigh and heart (5.71 +/- 0.8 mm vs 5.95 +/- 1.3 mm, respectively; P = .18).
      The planar cross-sectional lesion area was greater in the thigh model (thigh 54.8
      +/- 10.8 mm2 vs heart 43.1 +/- 16.1 mm2; P <.001). At the high-energy setting,
      lesion depth, width, and area were all greater in the thigh model (thigh 91.5 +/-
      16.8 mm2 vs heart 56.0 +/- 15.5 mm2; P <.001). The incidence of steam pop and
      char formation was similar between the models. CONCLUSION: The thigh preparation
      model is a reasonable technique for evaluation of ablation catheter technology;
      however it often results in overestimation of lesion size, especially at higher
      energy settings.

PMID- 28455272
TI  - The need for MR conditional devices: a sand castle at the seashore?

PMID- 28455273
TI  - Exploring Workarounds Related to Electronic Health Record System Usage: A Study
      Protocol.
AB  - BACKGROUND: Health care providers resort to informal temporary practices known as
      workarounds for handling exceptions to normal workflow that are unintentionally
      imposed by electronic health record (EHR) systems. Although workarounds may seem
      favorable at first sight, they are generally suboptimal and may jeopardize
      patient safety, effectiveness, and efficiency of care. Identifying workarounds
      and understanding their motivations, scope, and impact is pivotal to support the
      design of user-friendly EHRs and achieve closer alignment between EHRs and work
      contexts. OBJECTIVE: We propose a study protocol to identify EHR workarounds and
      subsequently determine their scope and impact on health care providers'
      workflows, patient safety, effectiveness, and efficiency of care. First, knowing
      whether a workaround solely affects the health care provider who devised it, or
      whether its effects extends beyond the EHR user to the work context of other
      health care providers, is key to accurately assessing its degree of influence on
      the overall patient care workflow. Second, knowing whether the consequence of an
      EHR workaround is favorable or unfavorable provides insights into how to address
      EHR-related safety, effectiveness, and efficiency concerns. Knowledge of both
      perspectives can provide input on optimizing EHR designs. METHODS: In the study,
      a combination of direct observations, semistructured interviews, and qualitative
      coding techniques will be used to identify, analyze, and classify EHR
      workarounds. The research project will be conducted within three distinct
      pediatric care processes and settings at a large university hospital. RESULTS:
      Data was collected using the described approach from January 2016 to March 2017.
      Data analysis is underway and is expected to be completed in May 2017. We aim to
      report the results of this study in a follow-up publication. CONCLUSIONS: This
      study protocol provides a grounded framework to explore EHR workarounds from a
      holistic and integral perspective. Insights from this study can inform the design
      and redesign of EHRs to further align with work contexts of healthcare
      professionals, and subsequently lead to better organization and safer provision
      of care.

PMID- 28455274
TI  - Protocol of a Pilot Study of Technology-Enabled Coproduction in Pediatric Chronic
      Illness Care.
AB  - BACKGROUND: Pediatric chronic illness care models are traditionally organized
      around acute episodes of care and may not meet the needs of patients and their
      families. Interventions that extend the patient-clinician interaction beyond the
      health care visit, allow for asynchronous and bidirectional feedback loops that
      span visits and daily life, and facilitate seamless sharing of information are
      needed to support a care delivery system that is more collaborative, continuous,
      and data-driven. Orchestra is a mobile health technology platform and
      intervention designed to transform the management of chronic diseases by
      optimizing patient-clinician coproduction of care. OBJECTIVE: The aim of this
      study is to assess the feasibility, acceptability, and preliminary impact of the
      Orchestra technology and intervention in the context of pediatric chronic illness
      care. METHODS: This study will be conducted in the cystic fibrosis and
      inflammatory bowel disease clinics at Cincinnati Children's Hospital Medical
      Center. We will enroll interested patients and their caregivers to work with
      clinicians to use the Orchestra technology platform and care model over a 6-month
      period. In parallel, we will use quality improvement methods to improve processes
      for integrating Orchestra into clinic workflows and patient/family lifestyles. We
      will use surveys, interviews, technology use data, and measures of clinical
      outcomes to assess the feasibility, acceptability, and preliminary impact of
      Orchestra. Outcome measures will include assessments of: (1) enrollment and
      dropout rates; (2) duration of engagement/sustained use; (3) symptom and patient
      reported outcome tracker completion rates; (4) perceived impact on treatment
      plan, communication with the clinical team, visit preparation, and overall care;
      (5) changes in disease self-efficacy and engagement in care; and (6) clinical
      outcomes and health care utilization. RESULTS: Participant recruitment began in
      mid-2015, with results expected in 2017. CONCLUSIONS: Chronic disease management
      needs a dramatic transformation to support more collaborative, effective, and
      patient-centered care. This study is unique in that it is testing not only the
      impact of technology, but also the necessary processes that facilitate patient
      and clinician collaboration. This pilot study is designed to examine how
      technology-enabled coproduction can be implemented in real-life clinical
      contexts. Once the Orchestra technology and intervention are optimized to ensure
      feasibility and acceptability, future studies can test the effectiveness of this
      approach to improve patient outcomes and health care value.

PMID- 28455275
TI  - Association Between Workarounds and Medication Administration Errors in Bar Code
      Assisted Medication Administration: Protocol of a Multicenter Study.
AB  - BACKGROUND: Information technology-based methods such as bar code-assisted
      medication administration (BCMA) systems have the potential to reduce medication
      administration errors (MAEs) in hospitalized patients. In practice, however,
      systems are often not used as intended, leading to workarounds. Workarounds may
      result in MAEs that may harm patients. OBJECTIVE: The primary aim is to study the
      association of workarounds with MAEs in the BCMA process. Second, we will
      determine the frequency and type of workarounds and MAEs and explore the
      potential risk factors (determinants) for workarounds. METHODS: This is a
      multicenter prospective study on internal medicine and surgical wards of 4 Dutch
      hospitals using BCMA systems to administer medication. We will include a total of
      6000 individual drug administrations using direct observation to collect data.
      RESULTS: The project was funded in 2014 and enrollment was completed at the end
      of 2016. Data analysis is under way and the first results are expected to be
      submitted for publication at the end of 2017. CONCLUSIONS: If an association
      between workarounds and MAEs is established, this information can be used to
      reduce the frequency of MAEs. Information on determinants of workarounds can aid
      in a focused approach to reduce workarounds and thus increase patient safety.
      TRIAL REGISTRATION: Netherlands Trial Register NTR4355;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4355 (Archived by
      WebCite at http://www.webcitation.org/6pqTLxc6i).

PMID- 28455278
TI  - The Physical Activity Tracker Testing in Youth (P.A.T.T.Y.) Study: Content
      Analysis and Children's Perceptions.
AB  - BACKGROUND: Activity trackers are widely used by adults and several models are
      now marketed for children. OBJECTIVE: The aims of this study were to (1) perform
      a content analysis of behavioral change techniques (BCTs) used by three
      commercially available youth-oriented activity trackers and (2) obtain feedback
      describing children's perception of these devices and the associated websites.
      METHODS: A content analysis recorded the presence of 36 possible BCTs for the
      MovBand (MB), Sqord (SQ), and Zamzee (ZZ) activity trackers. In addition, 16
      participants (mean age 8.6 years [SD 1.6]; 50% female [8/16]) received all three
      trackers and were oriented to the devices and websites. Participants were
      instructed to wear the trackers on 4 consecutive days and spend >=10 min/day on
      each website. A cognitive interview and survey were administered when the
      participant returned the devices. Qualitative data analysis was used to analyze
      the content of the cognitive interviews. Chi-square analyses were used to
      determine differences in behavioral monitoring and social interaction features
      between websites. RESULTS: The MB, SQ, and ZZ devices or websites included 8, 15,
      and 14 of the possible 36 BCTs, respectively. All of the websites had a
      behavioral monitoring feature (charts for tracking activity), but the percentage
      of participants indicating that they "liked" those features varied by website
      (MB: 8/16, 50%; SQ: 6/16, 38%; ZZ: 11/16, 69%). Two websites (SQ and ZZ) included
      an "avatar" that the user could create to represent themselves on the website.
      Participants reported that they "liked" creating and changing their avatar (SQ:
      12/16, 75%, ZZ: 15/16, 94%), which was supported by the qualitative analyses of
      the cognitive interviews. Most participants (75%) indicated that they would want
      to wear the devices more if their friends were wearing a tracker. No significant
      differences were observed between SQ and ZZ devices in regards to liking or use
      of social support interaction features (P=.21 to .37). CONCLUSIONS: The websites
      contained several BCTs consistent with previously identified strategies. Children
      "liked" the social aspects of the websites more than the activity tracking
      features. Developers of commercial activity trackers for youth may benefit from
      considering a theoretical perspective during the website design process.

PMID- 28455276
TI  - Therapist-Supported Internet-Based Cognitive Behavior Therapy for Stress,
      Anxiety, and Depressive Symptoms Among Postpartum Women: A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: A growing number of meta-analyses have supported the application of
      therapist-supported Internet-based cognitive behavior therapy (iCBT) for
      psychological disorders across different populations, but relatively few meta
      analyses have concentrated on postpartum women. OBJECTIVE: This meta-analysis
      evaluated the efficacy of therapist-supported iCBT in improving stress, anxiety,
      and depressive symptoms among postpartum women. METHODS: A total of 10 electronic
      databases were used to search for published and unpublished trials. Cochrane
      Collaboration tool for assessing risk of bias was utilized to measure
      methodological quality. Meta-analysis was performed using the RevMan software
      (Review Manager version 5.3 for Windows from the Nordic Cochrane Centre, the
      Cochrane Collaboration, 2014). Among the 789 studies identified, 8 randomized
      controlled trials were selected, involving 1523 participants across 6 countries.
      RESULTS: More than half (65%) of the eligible studies had a low risk of bias with
      no heterogeneity. Results revealed that therapist-supported iCBT significantly
      improved stress (d=0.84, n=5), anxiety (d=0.36, n=6), and depressive symptoms
      (d=0.63, n=8) of the intervention group compared with those of the control group
      at post-intervention. CONCLUSIONS: This review revealed that therapist-supported
      iCBT significantly improves stress, anxiety, and depressive symptoms among
      postpartum women with small to large effects. Future effectiveness studies should
      establish the essential components, format, and approach of iCBT with optimal
      levels of human support to maximize a long-term effect.

PMID- 28455277
TI  - Evidence of Benefit of Telerehabitation After Orthopedic Surgery: A Systematic
      Review.
AB  - BACKGROUND: In addition to traditional physiotherapy, studies based on
      telerehabilitation programs have published the results of effectiveness,
      validity, noninferiority, and important advantages in some neurological,
      cognitive, and musculoskeletal disorders, providing an opportunity to define new
      social policies and interventions. OBJECTIVES: The aim of this systematic review
      is to investigate the effects of telerehabilitation after surgical procedures on
      orthopedic conditions as well as to describe how interventions are designed and
      to determine whether telerehabilitation is comparable with conventional methods
      of delivery. This systematic review summarizes the levels of evidence and grades
      of recommendation regarding telerehabilitation intervention (synchronous or
      asynchronous provided via the telerehabilitation medium, either in conjunction
      with, or in isolation of, other treatment interventions) after surgical
      procedures on orthopedic conditions. METHODS: Study quality was assessed using
      the Physiotherapy Evidence Database (PEDro) scores and grade of recommendation
      following the recommendation of the Oxford Centre for Evidence-Based Medicine.
      RESULTS: We found 3 studies with PEDro scores between 6 and 8, which is
      considered as level 1 evidence (good; 20% [3/15]), 4 studies with a score of 5,
      which is considered as level 2 evidence (acceptable; 27% [4/15]), and the
      remaining 8 studies had scores of 4 or less, which is considered (poor; 53%
      [8/15]). A total of 1316 participants received telerehabilitation intervention in
      the selected studies, where knee and hip replacement were 75% of all the studies.
      Strong and moderate grades of evidence (grade of recommendation A-B) were found
      in knee and hip replacement interventions. Studies on the upper limb were 25% of
      the studies, but only 1 study presented a moderate grade of evidence (grade of
      recommendation B) and the rest were of poor methodological quality with weak
      evidence (grade of recommendation C). CONCLUSIONS: Conclusive evidence on the
      efficacy of telerehabilitation for treatment after an orthopedic surgery,
      regardless of pathology, was not obtained. We found strong evidence in favor of
      telerehabilitation in patients following total knee and hip arthroplasty and
      limited evidence in the upper limb interventions (moderate and weak evidence).
      Future research needs to be more extensive and conclusive. To the best of the
      authors' knowledge, this is the first attempt at evaluating the quality of
      telerehabilitation intervention research after surgical procedures on orthopedic
      conditions in a systematic review. Clinical messages and future research
      recommendations are included in the review.

PMID- 28455279
TI  - Engaging Patients and Caregivers Managing Rare Diseases to Improve the Methods of
      Clinical Guideline Development: A Research Protocol.
AB  - BACKGROUND: Clinical guidelines provide systematically developed recommendations
      for deciding on appropriate health care options for specific conditions and
      clinical circumstances. Up until recently, patients and caregivers have rarely
      been included in the process of developing care guidelines. OBJECTIVE: This
      project will develop and test a new online method for including patients and
      their caregivers in this process using Duchenne muscular dystrophy (DMD) care
      guidelines as an example. The new method will mirror and complement the RAND/UCLA
      Appropriateness Method (RAM)-the gold standard approach for conducting clinical
      expert panels that uses a modified Delphi format. RAM is often used in clinical
      guideline development to determine care appropriateness and necessity in
      situations where existing clinical evidence is uncertain, weak, or unavailable.
      METHODS: To develop the new method for engaging patients and their caregivers in
      guideline development, we will first conduct interviews with experts on RAM,
      guideline development, patient engagement, and patient-centeredness and engage
      with Duchenne patients and caregivers to identify how RAM should be modified for
      the purposes of patient engagement and what rating criteria should patients and
      caregivers use to provide their input during the process of guideline
      development. Once the new method is piloted, we will test it by conducting two
      concurrently run patient/caregiver panels that will rate patient-centeredness of
      a subset of DMD care management recommendations already deemed clinically
      appropriate and necessary. The ExpertLensTM system-a previously evaluated online
      modified Delphi system that combines two rounds of rating with a round of
      feedback and moderated online discussions-will be used to conduct these panels.
      In addition to developing and testing the new engagement method, we will work
      with the members of our project's Advisory Board to generate a list of best
      practices for enhancing the level of patient and caregiver involvement in the
      guideline development process. We will solicit input on these best practice from
      Duchenne patients, caregivers, and clinicians by conducting a series of round
      table discussions and making a presentation at an annual conference on Duchenne.
      RESULTS: The study protocol was reviewed by RAND's Human Subjects Protection
      Committee, which determined it to be exempt from review. Interviews with RAM
      experts have been completed. The projected study completion date is May 2020.
      CONCLUSIONS: We expect that the new method will make it easier to engage large
      numbers of patients and caregivers in the process of guideline development in a
      rigorous and culturally appropriate manner that is consistent with the way
      clinicians participate in guideline development. Moreover, this project will
      develop best practices that could help involve patients and caregivers in the
      clinical guideline development process in other clinical areas, thereby
      facilitating the work of guideline developers.

PMID- 28455280
TI  - "The patient is speaking": discovering the patient voice in ophthalmology.
AB  - Eye disease can be devastating. The most feared impact is sight loss, but in a
      number of ophthalmic conditions, there can be wide-ranging systemic,
      psychological, emotional and social effects of both the disease and its
      treatment. External tests of visual function, such as visual acuity, are
      inadequate to understand the overall impact of ophthalmic disease on a patient's
      functional vision or daily life. This can lead to a discordance between the
      patient's priorities and perspective on the one hand and the efforts of
      clinicians and other stakeholders on the other hand. In this review, we discuss
      how the patient is uniquely placed to understand the impact of the disease and
      can use that position to transform ophthalmic care at the individual and
      collective level, from research to care delivery. We highlight how the "patient
      voice" can contribute to key areas, including priority setting in the research
      agenda, communicating the wide-ranging impact of disease and its treatment as
      assessed through qualitative research, identifying the outcome measures that
      matter to the patient through core outcome set development and reporting these
      outcomes through appropriate patient-reported outcome measures. We also consider
      the increasing power of the patient voice on health institutions, ranging from
      broadcasting an individual's experience of care he/she has received to patient
      societies influencing future health policy. Finally, we reflect on the challenges
      that need to be overcome for the patient voice to increasingly influence and
      improve the delivery of eye care in the future.

PMID- 28455281
TI  - Cardiometabolic Disease Staging Predicts Effectiveness of Weight-Loss Therapy to
      Prevent Type 2 Diabetes: Pooled Results From Phase III Clinical Trials Assessing
      Phentermine/Topiramate Extended Release.
AB  - OBJECTIVE: To assess the ability of medication-assisted weight loss to prevent
      diabetes as a function of the baseline weighted Cardiometabolic Disease Staging
      (CMDS) score. RESEARCH DESIGN AND METHODS: We pooled data from 3,040 overweight
      and obese participants in three randomized controlled trials-CONQUER, EQUIP, and
      SEQUEL-assessing efficacy and safety of phentermine/topiramate extended release
      (ER) for weight loss. In these double-blind phase III trials, overweight/obese
      adult patients were treated with a lifestyle intervention and randomly assigned
      to placebo versus once-daily oral phentermine/topiramate ER. The weighted CMDS
      score was calculated using baseline quantitative clinical data including waist
      circumference, blood glucose, blood pressure, and blood lipids. Incident diabetes
      was defined based on serial measures of fasting glucose, 2-h oral glucose
      tolerance test glucose, and/or HbA1c. RESULTS: The absolute decrease in 1-year
      diabetes incidence rates in subjects treated with medication versus placebo was
      greatest in those with high-risk CMDS scores at baseline (10.43-6.29%),
      intermediate in those with moderate CMDS risk (4.67-2.37%), and small in the low
      risk category (1.51-0.67%). The number of participants needed to treat to prevent
      one new case of diabetes over a 56-week period was 24, 43, and 120 in those with
      baseline CMDS scores of >=60, 30-59, and 0-29, respectively. CONCLUSIONS: Numbers
      needed to treat to prevent one case of type 2 diabetes are markedly lower in
      patients with high-risk scores. CMDS can be used to quantify risk of diabetes in
      overweight/obese individuals and predict the effectiveness of weight-loss therapy
      to prevent diabetes.

PMID- 28455283
TI  - Workload pressure no defence against clinical negligence, barrister warns.

PMID- 28455284
TI  - A multidisciplinary approach to reducing alarm fatigue and cost through
      appropriate use of cardiac telemetry.
AB  - BACKGROUND: Alarm fatigue (AF) is a distressing factor for staff and patients in
      the hospital. Using cardiac telemetry (CT) without clinical indications can
      create unnecessary alarms, and increase AF and cost of healthcare. We sought to
      reduce AF and cost associated with CT monitoring. METHODS: After implementing a
      new protocol for CT placement, data were collected on telemetry orders, alarms
      and bed cost for 13 weeks from 1 January 2015 through 31 March 2015. We also
      retrospectively collected data on the same variables for the 13 weeks prior to
      the intervention. A survey was administered to nurses to assess past and present
      perceptions of AF. Interventions included protocol creation and education for
      participants. RESULTS: At baseline, 77% of patients were monitored with CT. A
      total of 145 (31%) order discrepancies were discovered during data collection, of
      which 72% had no indication for CT, so CT was discontinued. The other 28% had
      indications, so orders were placed. A total of 8336 alarms were recorded during 4
      weeks of data collection, of which 333 (4%) were classified as true actionable
      alarms. Postintervention data showed 67% CT assignment with 10% reduction in CT
      usage, with no increase in mortality (p<0.001 and >0.05, respectively). A 42%
      cost reduction was achieved after adjusting the patient status. Nurses reported
      27% perceived reduction in AF. One-year follow-up revealed that 69% of patients
      were being monitored by CT, and the rate of order discrepancies due to lack of
      indication was 9%. CONCLUSION: All hospital units may benefit from the protocols
      created during this study. If applied appropriately, these protocols can lead to
      reduced AF and cost per episode of care.

PMID- 28455285
TI  - Association of HLA-DQB1 polymorphisms with rheumatoid arthritis: a meta-analysis.
AB  - AIM: Studies investigating the association between HLA-DQB1 alleles and
      rheumatoid arthritis (RA) have reported conflicting results. The purpose of this
      study was to evaluate whether DQB1 alleles confer susceptibility to RA. DESIGN: A
      comprehensive literature search up to May 2016 was conducted to identify case
      control studies on the association of HLA-DQB1 alleles with RA. Pooled ORs with
      95% CIs were used to assess the strength of association. SETTING: The literature
      indicates that HLA-DQB1 is associated with susceptibility to RA. MAIN OUTCOME
      MEASURES: Frequencies of HLA-DQB1 alleles and phenotype in RA patients and
      healthy controls. RESULTS: Fifteen studies with 1250 cases and 1621 controls were
      included in this meta-analysis. DQB1 alleles were associated with RA
      susceptibility. The frequencies of DQB1*06 were lower in RA (p-value for
      comparability=0.007, OR 0.726,95% CI 0.576 to 0.916; p=0.004, OR 0.611,95% CI
      0.438 to 0.852). The frequencies of DQB1*02 were lower in RA (p=0.044, OR
      0.731,95% CI 0.597 to 0.895). A higher frequency of DQB1*04 was observed in RA
      (p=0.023, OR 1.604,95% CI 1.067 to 2.410). CONCLUSIONS: This meta-analysis
      demonstrates that DQB1*02 and DQB1*06 may be negatively associated with RA.
      Conversely, DQB1*04 may confer susceptibility to RA.

PMID- 28455282
TI  - Identifying and enriching platelet-producing human stem cell-derived
      megakaryocytes using factor V uptake.
AB  - Stem cell-derived platelets have the potential to replace donor platelets for
      transfusion. Defining the platelet-producing megakaryocytes (MKs) within the
      heterogeneous MK culture may help to optimize the in vitro generation of
      platelets. Using 2 human stem cell models of megakaryopoiesis, we identified
      novel MK populations corresponding to distinct maturation stages. An immature,
      low granular (LG) MK pool (defined by side scatter on flow cytometry) gives rise
      to a mature high granular (HG) pool, which then becomes damaged by apoptosis and
      glycoprotein Ib alpha chain (CD42b) shedding. We define an undamaged HG/CD42b+ MK
      subpopulation, which endocytoses fluorescently labeled coagulation factor V (FV)
      from the media into alpha-granules and releases functional FV+CD42b+ human
      platelet-like particles in vitro and when infused into immunodeficient mice.
      Importantly, these FV+ particles have the same size distribution as infused human
      donor platelets and are preferentially incorporated into clots after laser
      injury. Using drugs to protect HG MKs from apoptosis and CD42b shedding, we also
      demonstrate that apoptosis precedes CD42b shedding and that apoptosis inhibition
      enriches the FV+ HG/CD42b+ MKs, leading to increased platelet yield in vivo, but
      not in vitro. These studies identify a transition between distinct MK populations
      in vitro, including one that is primed for platelet release. Technologies to
      optimize and select these platelet-ready MKs may be important to efficiently
      generate functional platelets from in vitro-grown MKs.

PMID- 28455286
TI  - Ultrasound biomicroscopy validation of a murine model of cardiac hypertrophic
      preconditioning: comparison with a hemodynamic assessment.
AB  - In mice, myocardial hypertrophic preconditioning (HP), which is produced by the
      removal of short-term transverse aortic constriction (TAC), was recently reported
      to render the heart resistant to hypertrophic responses induced by subsequent
      reconstriction (Re-TAC). However, there is no efficient noninvasive method for
      ensuring that the repeated aortic manipulations were successfully performed. We
      previously demonstrated that ultrasound biomicroscopy (UBM) is a noninvasive and
      effective approach for predicting TAC success. Here, we investigated the value of
      UBM for serial predictions of load conditions in establishing a murine HP model.
      C57BL/6J mice were subjected to a sham operation, TAC, or Re-TAC, and the peak
      flow velocity at the aortic banding site (PVb) was measured by UBM. Left
      ventricular end-systolic pressure (LVESP) was examined by micromanometric
      catheterization. The PVb was positively associated with LVESP (R2 = 0.8204, P <
      0.001, for TAC at 3 days and R2 = 0.7746, P < 0.001, for Re-TAC at 4 wk). PVb and
      LVESP values were markedly elevated after aortic banding, became attenuated to
      the sham-operated level after debanding, and increased after aortic rebanding.
      The cardiac hypertrophic responses were examined by UBM, histology, RT-PCR, and
      Western blot analysis. Four weeks after the last operation, with PVb >= 3.5 m/s
      as an indicator of successful aortic constriction, Re-TAC mice showed less
      cardiac hypertrophy, fetal gene expression, and ERK1/2 activation than TAC mice.
      Therefore, we successfully established a UBM protocol for the serial assessment
      of aortic flow and the prediction of LVESP during repeated aortic manipulations
      in mice, which might be useful for noninvasive evaluations of the murine HP
      model.NEW & NOTEWORTHY We successfully developed an ultrasound biomicroscopy
      protocol for the serial assessment of aortic bandings and the relevant left
      ventricular pressure in a murine model of cardiac hypertrophic preconditioning.
      The protocol may be of great importance in the successful establishment of the
      hypertrophic preconditioning model for further mechanistic and pharmacological
      studies.

PMID- 28455287
TI  - Desmin loss and mitochondrial damage precede left ventricular systolic failure in
      volume overload heart failure.
AB  - Heart failure due to chronic volume overload (VO) in rats and humans is
      characterized by disorganization of the cardiomyocyte desmin/mitochondrial
      network. Here, we tested the hypothesis that desmin breakdown is an early and
      continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula
      (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later.
      Desmin/mitochondrial ultrastructure was examined by transmission electron
      microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were
      performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass
      spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40%
      decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with
      ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4
      and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering,
      IHC evidence of disorganization associated with desmin breakdown, and desmin
      protein cleavage verified by Western blot analysis and mass spectrometry. IHC
      results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear
      translocation of alphaB-crystallin from the Z disk with increased alpha, beta
      unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification
      by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte
      apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of
      mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is
      indicative of an inability to complete autophagy. An early and continuous
      disruption of the desmin/mitochondrial architecture, accompanied by oxidative
      stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV
      dilatation and systolic dysfunction in VO.NEW & NOTEWORTHY This study provides
      new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement
      and disruption of the normal sarcomeric and mitochondrial architecture throughout
      the progression of volume overload heart failure, suggesting a causal link
      between desmin cleavage and mitochondrial disorganization and damage.

PMID- 28455288
TI  - Cardiac myofibrillar contractile properties during the progression from
      hypertension to decompensated heart failure.
AB  - Heart failure arises, in part, from a constellation of changes in cardiac
      myocytes including remodeling, energetics, Ca2+ handling, and myofibrillar
      function. However, little is known about the changes in myofibrillar contractile
      properties during the progression from hypertension to decompensated heart
      failure. The aim of the present study was to provide a comprehensive assessment
      of myofibrillar functional properties from health to heart disease. A rodent
      model of uncontrolled hypertension was used to test the hypothesis that myocytes
      in compensated hearts exhibit increased force, higher rates of force development,
      faster loaded shortening, and greater power output; however, with progression to
      overt heart failure, we predicted marked depression in these contractile
      properties. We assessed contractile properties in skinned cardiac myocyte
      preparations from left ventricles of Wistar-Kyoto control rats and spontaneous
      hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate
      the time course of myofilament properties associated with normal aging processes
      compared with myofilaments from rats with a predisposition to heart failure. In
      control rats, the myofilament contractile properties were virtually unchanged
      throughout the aging process. Conversely, in SHHF rats, the rate of force
      development, loaded shortening velocity, and power all increased at ~12 mo and
      then significantly fell at the >20-mo time point, which coincided with a decrease
      in left ventricular fractional shortening. Furthermore, these changes occurred
      independent of changes in beta-myosin heavy chain but were associated with
      depressed phosphorylation of myofibrillar proteins, and the fall in loaded
      shortening and peak power output corresponded with the onset of clinical signs of
      heart failure.NEW & NOTEWORTHY This novel study systematically examined the power
      generating capacity of cardiac myofilaments during the progression from
      hypertension to heart disease. Previously undiscovered changes in myofibrillar
      power output were found and were associated with alterations in myofilament
      proteins, providing potential new targets to exploit for improved ventricular
      pump function in heart failure.

PMID- 28455289
TI  - Diminished responsiveness to dobutamine as an inotrope in mice with cecal
      ligation and puncture-induced sepsis: attribution to phosphodiesterase 4
      upregulation.
AB  - Dobutamine has been used in septic shock for many years as an only inotrope, but
      its benefit has been questioned. We weighed the effects of dobutamine and
      milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced
      polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac
      inflammation, as indicated by greatly increased mRNAs of proinflammatory
      cytokines and robust infiltration of inflammatory cells in the ventricular
      myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP
      mice. Noninvasive echocardiographic assessment of cardiac function revealed that
      despite preserved left ventricular function in the presence of fluid replacement,
      the dobutamine inotropic response was significantly impaired in CLP mice compared
      with sham-operated controls. By contrast, milrinone exerted inotropic effects in
      sham-operated and CLP mice in an equally effective manner. Surface expression
      levels of beta1-adrenoceptors and alpha-subunits of three main G protein families
      in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were
      significantly elevated in both sham-operated and CLP mice in response to
      milrinone but only in sham-operated controls in response to dobutamine. Of
      phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are
      responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP
      mouse myocardium. We define a novel mechanism for the impaired responsiveness to
      dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in
      modulating cardiac functional responsiveness in sepsis may open the potential of
      a PDE4D-targeted therapeutic option in septic patients with low cardiac output
      who have a need for inotropic support.NEW & NOTEWORTHY Advisability of the
      usefulness of dobutamine in septic shock management is limited. Here, we reveal
      that the effect of dobutamine as a positive inotrope is impaired in mice with
      cecal ligation and puncture-induced sepsis without changes in cardiac beta1
      adrenoceptor signaling as a result of cAMP breakdown achieved by upregulated
      phosphodiesterase 4D.

PMID- 28455290
TI  - Quantitative cardiac phosphoproteomics profiling during ischemia-reperfusion in
      an immature swine model.
AB  - Ischemia-reperfusion (I/R) results in altered metabolic and molecular responses,
      and phosphorylation is one of the most noted regulatory mechanisms mediating
      signaling mechanisms during physiological stresses. To expand our knowledge of
      the potential phosphoproteomic changes in the myocardium during I/R, we used
      Isobaric Tags for Relative and Absolute Quantitation-based analyses in left
      ventricular samples obtained from porcine hearts under control or I/R conditions.
      The data are available via ProteomeXchange with identifier PXD006066. We
      identified 1,896 phosphopeptides within left ventricular control and I/R porcine
      samples. Significant differential phosphorylation between control and I/R groups
      was discovered in 111 phosphopeptides from 86 proteins. Analysis of the
      phosphopeptides using Motif-x identified five motifs: (..R..S..), (..SP..),
      (..S.S..), (..S...S..), and (..S.T..). Semiquantitative immunoblots confirmed
      site location and directional changes in phosphorylation for phospholamban and
      pyruvate dehydrogenase E1, two proteins known to be altered by I/R and identified
      by this study. Novel phosphorylation sites associated with I/R were also
      identified. Functional characterization of the phosphopeptides identified by our
      methodology could expand our understanding of the signaling mechanisms involved
      during I/R damage in the heart as well as identify new areas to target
      therapeutic strategies.NEW & NOTEWORTHY We used Isobaric Tags for Relative and
      Absolute Quantitation technology to investigate the phosphoproteomic changes that
      occur in cardiac tissue under ischemia-reperfusion conditions. The results of
      this study provide an extensive catalog of phosphoproteins, both predicted and
      novel, associated with ischemia-reperfusion, thereby identifying new pathways for
      investigation.

PMID- 28455292
TI  - betahCG-secreting osteosarcoma.
AB  - A 35-year-old woman presented to our institution with tender, right knee
      swelling. Radiological and pathological work-up revealed metastatic osteosarcoma.
      Prior to the initiation of chemotherapy, she underwent a routine urine pregnancy
      test and was surprised with a positive result. Serum beta human chorionic
      gonadotropin (betahCG) levels were also consistently positive and rising. No
      gestational sac was seen at transvaginal ultrasound. The paraneoplastic ectopic
      secretion of betahCG has been well described in gestational trophoblastic and
      gonadal tumours but has very rarely been associated with other tumour types. This
      patient's betahCG level was reflective of osteosarcoma activity and normalised
      with response to chemotherapy. The prognostic implications of betahCG expression
      in more diverse tumours is unclear; however, where raised, it can be used to
      monitor disease activity.

PMID- 28455291
TI  - Hyper-phosphorylation of Sequestosome-1 Distinguishes Resistance to Cisplatin in
      Patient Derived High Grade Serous Ovarian Cancer Cells.
AB  - Platinum-resistance is a major limitation to effective chemotherapy regimens in
      high-grade serous ovarian cancer (HGSOC). To better understand the mechanisms
      involved we characterized the proteome and phosphoproteome in cisplatin sensitive
      and resistant HGSOC primary cells using a mass spectrometry-based proteomic
      strategy. PCA analysis identified a distinctive phosphoproteomic signature
      between cisplatin sensitive and resistant cell lines. The most phosphorylated
      protein in cisplatin resistant cells was sequestosome-1 (p62/SQSTM1). Changes in
      expression of apoptosis and autophagy related proteins Caspase-3 and SQSTM1,
      respectively, were validated by Western blot analysis. A significant increase in
      apoptosis in the presence of cisplatin was observed in only the sensitive cell
      line while SQSTM1 revealed increased expression in the resistant cell line
      relative to sensitive cell line. Furthermore, site-specific phosphorylation on 20
      amino acid residues of SQSTM1 was detected indicating a hyper-phosphorylation
      phenotype. This elevated hyper-phosphorylation of SQSTM1 in resistant HGSOC cell
      lines was validated with Western blot analysis. Immunofluoresence staining of s28
      pSQSTM1 showed inducible localization to autophagosomes upon cisplatin treatment
      in the sensitive cell line while being constitutively expressed to autophagosomes
      in the resistant cell. Furthermore, SQSTM1 expression was localized in cancer
      cells of clinical high-grade serous tumors. Here, we propose hyper
      phosphorylation of SQSTM1 as a marker and a key proteomic change in cisplatin
      resistance development in ovarian cancers by activating the autophagy pathway and
      influencing down-regulation of apoptosis.

PMID- 28455293
TI  - True Anemia-Red Blood Cell Volume Deficit-in Heart Failure: A Systematic Review.
AB  - BACKGROUND: Anemia in heart failure (HF) is commonly diagnosed according to
      hemoglobin concentration [Hb], hence may be the result of hemodilution or true
      red blood cell volume (RBCV) deficit. Whether true (nonhemodilutional) anemia in
      HF can or cannot be generally inferred by [Hb] measurements and clinical
      correlates remains unclear. The purpose of this study was to systematically
      review the literature and investigate the status and correlates of RBCV in
      patients with HF. METHODS AND RESULTS: MEDLINE, Scopus, and Web of Science were
      searched since their inceptions until April 2016 for articles directly reporting
      or allowing the calculation of intravascular volumes (RBCV, plasma volume) in
      patients with HF according to the International Council for Standardization in
      Hematology. Eighteen studies were included after systematic review, comprising a
      total of 368 patients with HF (limits for mean age=49-80 years, sex=0%-92%
      females, left ventricular ejection fraction=26%-61%). Mean RBCV was reduced
      (limits=67%-88% of normal) in all studies including HF patients with anemia (low
      [Hb]) (7 studies, n=127), whereas only 2 of 10 studies in nonanemic patients with
      HF presented lower than normal mean RBCV (90% and 96%). In metaregression
      analyses, RBCV was positively associated with [Hb] (B=6.10, SE=1.44) and
      negatively associated with age (B=-1.14, SE=0.23), % females (B=-0.38, SE=0.04),
      left ventricular ejection fraction (B=-0.81, SE=0.20), and body mass index (B=
      3.55, SE=0.46; P<0.001). CONCLUSIONS: Presence or absence of true anemia in
      patients with HF as determined by RBCV status mainly concurs with diagnosis based
      on [Hb] and presents negative relationships with age, female sex, left
      ventricular ejection fraction, and body mass index.

PMID- 28455294
TI  - Stroke volume index in mild-moderate aortic stenosis: more than a barometer of
      systolic function?

PMID- 28455295
TI  - Impact of stroke volume on cardiovascular risk during progression of aortic valve
      stenosis.
AB  - OBJECTIVE: In severe aortic valve stenosis (AS), low left ventricular (LV) stroke
      volume has been associated with increased cardiovascular (CV) mortality, but this
      association has not been explored during progression of AS in a large prospective
      study. METHODS: In 1671 patients from the Simvastatin Ezetimibe in Aortic
      Stenosis (SEAS) study, the association of stroke volume indexed for body surface
      area (SVI) with major CV events during a median of 4.3-year follow-up was
      assessed in Cox and time-varying Cox regression analyses. Low SVI was defined as
      <35 mL/m2. RESULTS: Peak aortic jet velocity in the total study population was
      3.1 +/-0.7 m/s. Low SVI was found in 23% at baseline and associated with higher
      age, body mass index (BMI), heart rate and global LV load, and with lower mean
      aortic gradient, aortic valve area index, energy loss index, LV mass and ejection
      fraction and more often inconsistent AS grading (all p<0.05). A 5 mL/m2 lower SVI
      at baseline was associated with higher HRs of major CV events (n=544) (HR 1.09,
      95% CI 1.05 to 1.13, p<0.001) and higher total mortality (n=147) (HR 1.08, 95% CI
      1.01 to 1.16, p=0.038), independent of age, sex, atrial fibrillation, mean aortic
      gradient, LV ejection fraction, LV mass, BMI and study treatment. Adjusting for
      the same covariates, low SVI at baseline and in-study low SVI were also
      associated with increased rate of major CV events. CONCLUSION: In patients with
      AS in the SEAS study, lower baseline SVI was associated with higher HR of major
      CV events and total mortality independent of major confounders. TRIAL
      REGISTRATION NUMBER: NCT00092677: Results.

PMID- 28455296
TI  - Streamlining cardiovascular clinical trials to improve efficiency and
      generalisability.
AB  - Controlled trials provide the most valid determination of the efficacy and safety
      of an intervention, but large cardiovascular clinical trials have become
      extremely costly and complex, making it difficult to study many important
      clinical questions. A critical question, and the main objective of this review,
      is how trials might be simplified while maintaining randomisation to preserve
      scientific integrity and unbiased efficacy assessments. Experience with
      alternative approaches is accumulating, specifically with registry-based
      randomised controlled trials that make use of data already collected. This
      approach addresses bias concerns while still capitalising on the benefits and
      efficiencies of a registry. Several completed or ongoing trials illustrate the
      feasibility of using registry-based controlled trials to answer important
      questions relevant to daily clinical practice. Randomised trials within
      healthcare organisation databases may also represent streamlined solutions for
      some types of investigations, although data quality (endpoint assessment) is
      likely to be a greater concern in those settings. These approaches are not
      without challenges, and issues pertaining to informed consent, blinding, data
      quality and regulatory standards remain to be fully explored. Collaboration among
      stakeholders is necessary to achieve standards for data management and analysis,
      to validate large data sources for use in randomised trials, and to re-evaluate
      ethical standards to encourage research while also ensuring that patients are
      protected. The rapidly evolving efforts to streamline cardiovascular clinical
      trials have the potential to lead to major advances in promoting better care and
      outcomes for patients with cardiovascular disease.

PMID- 28455297
TI  - Enlarged left atrium, atrial fibrillation and adverse outcome in hypertrophic
      cardiomyopathy: is there a difference between apical and non-apical phenotype?

PMID- 28455298
TI  - It is not how old you are, it is how you are old: need for changes in the
      management of infective endocarditis in the elderly.

PMID- 28455299
TI  - Basil Doumas.

PMID- 28455300
TI  - A Case of Unusual Drug Screening Results.

PMID- 28455301
TI  - Commentary.

PMID- 28455302
TI  - Commentary.

PMID- 28455303
TI  - Intracellular Inclusions Detected in Stained Urinary Sediment.

PMID- 28455304
TI  - Home or Hospital? Point-of-Care CRP as a Triage Biomarker in the Primary Care
      Setting.

PMID- 28455305
TI  - Mapping Thermal Flow under the Skin.

PMID- 28455306
TI  - Photographic Film, Clinical Chemistry, and Art.

PMID- 28455307
TI  - Edward Hopper: American Spaces.

PMID- 28455308
TI  - Most drugs paid for by L1.27bn Cancer Drugs Fund had no "meaningful benefit".

PMID- 28455310
TI  - Exercise-induced modification of the skeletal muscle transcriptome in Arabian
      horses.
AB  - It has been found that Arabian and Thoroughbred horses differ in muscle fiber
      structure and thus in physiological changes occurring in muscles during exercise.
      The aim of the present study was to identify the global gene expression
      modifications that occur in skeletal muscle following a training regime to
      prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were
      compared between three time points of tissue collection: T0 (untrained horses),
      T1 (horses after intense gallop phase), and T2 (horses at the end of racing
      season), 23 samples in total. The numerous groups of exercise-regulated
      differentially expressed genes (DEGs) were related to muscle cell structure and
      signaling and included insulin-like growth factor 1 receptor (IGF1R), insulin
      receptor (INSR), transforming growth factor beta receptors 1 and 2 (TGFBR1,
      TGFBR2), vascular endothelial growth factor B (VEGFB); epidermal growth factor
      (EGF), hepatocyte growth factor (HGF), and vascular endothelial growth factor D
      (FIGF). In Arabian horses, exercise modified the expression of genes belonging to
      the PPAR signaling pathway (e.g., PPARA, PPARD, and PLIN2), calcium signaling
      pathway, and pathways associated with metabolic processes (e.g., oxidative
      phosphorylation, fatty acid metabolism, glycolysis/gluconeogenesis, and citrate
      cycle). According to detected gene expression modifications, our results
      suggested that in Arabian horses, exercise switches energy generation toward
      fatty acid utilization and enhances glycogen transport and calcium signaling. The
      use of the RNA-Seq approach in analyzing the skeletal muscle transcriptome
      allowed for the proposal of a panel of new candidate genes potentially related to
      body homeostasis maintenance and racing performance in Arabian horses.

PMID- 28455309
TI  - Molecular structure and function of big calcium-activated potassium channels in
      skeletal muscle: pharmacological perspectives.
AB  - The large-conductance Ca2+-activated K+ (BK) channel is broadly expressed in
      various mammalian cells and tissues such as neurons, skeletal muscles (sarco-BK),
      and smooth muscles. These channels are activated by changes in membrane
      electrical potential and by increases in the concentration of intracellular
      calcium ion (Ca2+). The BK channel is subjected to many mechanisms that add
      diversity to the BK channel alpha-subunit gene. These channels are indeed subject
      to alternative splicing, auxiliary subunits modulation, posttranslational
      modifications, and protein-protein interactions. BK channels can be modulated by
      diverse molecules that may induce either an increase or decrease in channel
      activity. The linkage of these channels to many intracellular metabolites and
      pathways, as well as their modulation by extracellular natural agents, have been
      found to be relevant in many physiological processes. BK channel diversity is
      obtained by means of alternative splicing and modulatory beta- and gamma
      subunits. The association of the alpha-subunit with beta- or with gamma-subunits
      can change the BK channel phenotype, functional diversity, and pharmacological
      properties in different tissues. In the case of the skeletal muscle BK channel
      (sarco-BK channel), we established that the main mechanism regulating BK channel
      diversity is the alternative splicing of the KCNMA1/slo1 gene encoding for the
      alpha-subunit generating different splicing isoform in the muscle phenotypes.
      This finding helps to design molecules selectively targeting the skeletal muscle
      subtypes. The use of drugs selectively targeting the skeletal muscle BK channels
      is a promising strategy in the treatment of familial disorders affecting muscular
      skeletal apparatus including hyperkalemia and hypokalemia periodic paralysis.

PMID- 28455311
TI  - Robert John Cairns.

PMID- 28455313
TI  - Transient transcription factor (OSKM) expression is key towards clinical
      translation of in vivo cell reprogramming.
AB  - Reprogramming adult, fully differentiated cells to pluripotency in vivo via
      Oct3/4, Sox2, Klf4 and c-Myc (OSKM) overexpression has proved feasible in various
      independent studies and could be used to induce tissue regeneration owing to the
      proliferative capacity and differentiation potential of the reprogrammed cells.
      However, a number of these reports have described the generation of teratomas
      caused by sustained reprogramming, which precludes the therapeutic translation of
      this technology. A recent study by the Izpisua-Belmonte laboratory described a
      cyclic regime for short-term OSKM expression in vivo that prevents complete
      reprogramming to the pluripotent state as well as tumorigenesis. We comment here
      on this and other studies that provide evidence that in vivo OSKM induction can
      enhance tissue regeneration, while avoiding the feared formation of teratomas.
      These results could inspire more research to explore the potential of in vivo
      reprogramming in regenerative medicine.

PMID- 28455312
TI  - Administration of RANKL boosts thymic regeneration upon bone marrow
      transplantation.
AB  - Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs),
      which result in delayed de novo thymopoiesis and a prolonged period of T-cell
      immunodeficiency. Understanding the mechanisms that govern thymic regeneration is
      of paramount interest for the recovery of a functional immune system notably
      after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL)
      is upregulated in CD4+ thymocytes and lymphoid tissue inducer (LTi) cells during
      the early phase of thymic regeneration. Importantly, whereas RANKL neutralization
      alters TEC recovery after irradiation, ex vivo RANKL administration during BMT
      boosts the regeneration of TEC subsets including thymic epithelial progenitor
      enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis.
      RANKL increases specifically in LTi cells, lymphotoxin alpha, which is critical
      for thymic regeneration. RANKL treatment, dependent on lymphotoxin alpha, is
      beneficial upon BMT in young and aged individuals. This study thus indicates that
      RANKL may be clinically useful to improve T-cell function recovery after BMT by
      controlling multiple facets of thymic regeneration.

PMID- 28455314
TI  - Sleep-Time Ambulatory BP Is an Independent Prognostic Marker of CKD.
AB  - The prognostic value of clinic and ambulatory BP in predicting incident CKD and
      whether CKD risk reduction associates with progressive treatment-induced decrease
      of clinic, awake, or asleep BP are unknown. We prospectively evaluated 2763
      individuals without CKD, 1343 men and 1420 women (mean+/-SD age: 51.5+/-14.3
      years old), with baseline ambulatory BP ranging from normotension to
      hypertension. On recruitment and annually thereafter (more frequently if
      hypertension treatment was adjusted on the basis of ambulatory BP), we
      simultaneously monitored BP and physical activity (wrist actigraphy) for 48 hours
      to accurately derive individualized mean awake and asleep BP. During a median 5.9
      year follow-up, 404 participants developed CKD. Mean asleep systolic BP was the
      most significant predictor of CKD in a Cox proportional hazard model adjusted for
      age, diabetes, serum creatinine concentration, urinary albumin concentration,
      previous cardiovascular event, and hypertension treatment time (on awakening
      versus at bedtime; per 1-SD elevation: hazard ratio, 1.44; 95% confidence
      interval, 1.31 to 1.56; P<0.001). The predictive values of mean clinic BP and
      mean awake or 48-hour ambulatory BP was not significant when corrected by mean
      asleep BP. Analyses of BP changes during follow-up revealed 27% reduction in the
      risk of CKD per 1-SD decrease in mean asleep systolic BP, independent of changes
      in mean clinic BP or awake ambulatory BP. In conclusion, sleep-time BP is a
      highly significant independent prognostic marker for CKD. Furthermore,
      progressive treatment-induced decrease of asleep BP, a potential therapeutic
      target requiring ambulatory BP evaluation, might be a significant method for
      reducing CKD risk.

PMID- 28455315
TI  - Wake-Up Stroke Is Associated With Greater Nocturnal Mean Arterial Pressure
      Variability.
AB  - BACKGROUND AND PURPOSE: Wake-up strokes (WUS) account for ~20% to 30% of ischemic
      strokes. Studies have shown that increased autonomic instability as measured by
      blood pressure variability (BPV) is greater in stroke patients than nonstroke
      patients, but no studies have compared BPV in WUS versus non-WUS patients.
      METHODS: From a single-center prospective registry, we identified consecutive
      ischemic stroke patients. BPV was calculated as the coefficient of variation of
      the mean arterial pressure during the first 24 hours after hospitalization. We
      assessed 24-hour BPV as a continuous measure and in quartiles in WUS versus non
      WUS patients using univariable and multivariable statistics. RESULTS: Among 369
      patients (64.9+/-16.5 years; 50.1% male; 64.7% white), 78 were WUS (21.1%).
      Clinical characteristics and medical history were not different between WUS and
      non-WUS patients except WUS patients were older (69.0 versus 63.8 years; P=0.015)
      and more frequently had previous ischemic stroke (29.5% versus 17.2%; P=0.012).
      Initial 24-hour BPV (11.77 versus 10.76; P=0.098) was similar between groups.
      However, WUS patients had greater nocturnal BPV (10.50 versus 8.95; P=0.030),
      whereas daytime BPV was similar between groups (10.96 versus 10.47, P=0.459). In
      multivariate analysis, the highest quartile (>=11.48 mm Hg) of nocturnal BPV was
      independently associated with WUS (adjusted odds ratio, 1.95; confidence
      interval, 1.13-3.39; P=0.017). CONCLUSIONS: In this single-center study, we
      observed that greater nocturnal BPV during the first 24 hours after
      hospitalization occurred in WUS than non-WUS patients. Nocturnal autonomic
      instability warrants further study as a potential mechanism of WUS.

PMID- 28455316
TI  - Response by Bai et al to Letter Regarding Article, "Rivaroxaban Versus Dabigatran
      or Warfarin in Real-World Studies of Stroke Prevention in Atrial Fibrillation:
      Systematic Review and Meta-Analysis".

PMID- 28455317
TI  - Letter by Machado-Alba et al Regarding Article, "Rivaroxaban Versus Dabigatran or
      Warfarin in Real-World Studies of Stroke Prevention in Atrial Fibrillation:
      Systematic Review and Meta-Analysis".

PMID- 28455318
TI  - Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in
      Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4
      Randomized Controlled Trials.
AB  - BACKGROUND AND PURPOSE: Patients undergoing carotid endarterectomy (CEA) for
      symptomatic stenosis of the internal carotid artery benefit from early
      intervention. Heterogeneous data are available on the influence of timing of
      carotid artery stenting (CAS) on procedural risk. METHODS: We investigated the
      association between timing of treatment (0-7 days and >7 days after the
      qualifying neurological event) and the 30-day risk of stroke or death after CAS
      or CEA in a pooled analysis of individual patient data from 4 randomized trials
      by the Carotid Stenosis Trialists' Collaboration. Analyses were done per
      protocol. To obtain combined estimates, logistic mixed models were applied.
      RESULTS: Among a total of 4138 patients, a minority received their allocated
      treatment within 7 days after symptom onset (14% CAS versus 11% CEA). Among
      patients treated within 1 week of symptoms, those treated by CAS had a higher
      risk of stroke or death compared with those treated with CEA: 8.3% versus 1.3%,
      risk ratio, 6.7; 95% confidence interval, 2.1 to 21.9 (adjusted for age at
      treatment, sex, and type of qualifying event). For interventions after 1 week,
      CAS was also more hazardous than CEA: 7.1% versus 3.6%, adjusted risk ratio, 2.0;
      95% confidence interval, 1.5 to 2.7 (P value for interaction with time interval
      0.06). CONCLUSIONS: In randomized trials comparing stenting with CEA for
      symptomatic carotid artery stenosis, CAS was associated with a substantially
      higher periprocedural risk during the first 7 days after the onset of symptoms.
      Early surgery is safer than stenting for preventing future stroke. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00190398;
      URL: http://www.controlled-trials.com. Unique identifier: ISRCTN57874028; Unique
      identifier: ISRCTN25337470; URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00004732.

PMID- 28455319
TI  - Oxygenation-Sensitive Magnetic Resonance Imaging in Acute Ischemic Stroke Using
      T2'/R2' Mapping: Influence of Relative Cerebral Blood Volume.
AB  - BACKGROUND AND PURPOSE: Quantitative T2'/R2' mapping detect locally increased
      concentrations of deoxygenated hemoglobin-causing a decrease of T2' and increase
      of R2'-and might reflect increased cerebral oxygen extraction fraction. Because
      increases of (relative) cerebral blood volume (rCBV) may influence T2' and R2'
      through accumulation of deoxygenated hemoglobin, we aimed to investigate the
      impact of rCBV on T2'/R2' in patients with ischemic stroke. METHODS: Data from
      patients with acute internal carotid artery and middle cerebral artery occlusion
      were analyzed. T2', R2', and rCBV were measured within the ischemic core,
      slightly and severely hypoperfused areas, and their relationship was examined.
      RESULTS: A strong negative correlation with rCBV was found for R2' (r=-0.544;
      P=0.002), and T2' correlated positively with rCBV (r=0.546; P=0.001) in time-to
      peak-delayed areas. T2'/R2' within hypoperfused tissue remained unchanged at
      normal or elevated rCBV levels. CONCLUSIONS: T2' decrease/R2' increase within
      hypoperfused areas in ischemic stroke is not caused by local elevations of rCBV
      but most probably only by increased cerebral oxygen extraction fraction. However,
      considering rCBV is crucial to assess extent of oxygen extraction fraction
      changes by means of T2'/R2'.

PMID- 28455320
TI  - CHA2DS2-VASc Score (Congestive Heart Failure, Hypertension, Age >=75 [Doubled],
      Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular
      Disease, Age 65-74, Female) for Stroke in Asian Patients With Atrial
      Fibrillation: A Korean Nationwide Sample Cohort Study.
AB  - BACKGROUND AND PURPOSE: The CHA2DS2-VASc stroke score (congestive heart failure,
      hypertension, age >=75 (doubled), diabetes mellitus, prior stroke or transient
      ischemic attack (doubled), vascular disease, age 65-74, female) is used in most
      guidelines for risk stratification in atrial fibrillation (AF), but most data for
      this score have been derived in Western populations. Ethnic differences in stroke
      risk may be present. Our objective was to investigate risk factors for stroke in
      AF and application of the CHA2DS2-VASc score in an Asian AF population from
      Korea. METHODS: A total of 5855 oral anticoagulant-naive nonvalvular AF patients
      aged >=20 years were enrolled from Korea National Health Insurance Service Sample
      cohort from 2002 to 2008 and were followed up until December 2013. RESULTS: The
      incidence rates (per 100 person-years) of ischemic stroke were 3.32 in the total
      population, being 0.23 in low-risk (CHA2DS2-VASc score 0 [male] or 1 [female])
      and 4.59 in high-risk patients (CHA2DS2-VASc >=2). Incidence rates of ischemic
      stroke or the composite thromboembolism end point showed a clear increase with
      increasing CHA2DS2-VASc score. On multivariable analysis, significant
      associations between CHA2DS2-VASc risk factors and ischemic stroke were observed;
      however, the significance of vascular disease or diabetes mellitus was attenuated
      after multivariate adjustment, and female sex (hazard ratio, 0.73; 95% confidence
      interval, 0.64-0.84) had a lower risk of ischemic stroke than males. Patients who
      were categorized as low risk consistently had an event rate <1% per year.
      CONCLUSIONS: The performance of CHA2DS2-VASc score in Asians is comparable with
      that in Western populations. The score shows good performance in defining the
      truly-low-risk AF patients for stroke/thromboembolism.

PMID- 28455322
TI  - Classification of Bleeding Events: Comparison of ECASS III (European Cooperative
      Acute Stroke Study) and the New Heidelberg Bleeding Classification.
AB  - BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) after acute ischemic stroke
      treatments represents a feared complication with possible prognostic
      implications. In recent years, ICHs were commonly classified according to the
      ECASS (European Cooperative Acute Stroke Study). To improve the clinical
      applicability and relevance, the new Heidelberg Bleeding Classification (HBC) has
      been proposed in 2015. Here, we compared the ECASS and HBC classification with
      regard to observed events and prognostic relevance. METHODS: A retrospective
      analysis of a prospectively compiled database of patients with acute ischemic
      stroke in the anterior circulation who received mechanical thrombectomy between
      February 2011 and March 2016 was performed. Presence of ICH after mechanical
      thrombectomy was evaluated on postinterventional computed tomographic imaging.
      ICHs were specified according to both ECASS III and HBC classification and
      analyzed with regard to their symptoms and outcome. RESULTS: ICHs were observed
      in 156 of 768 patients (20.3%). Using ECASS III classification, 101 ICHs could be
      unambiguously assigned, of which 28 (27.7%; 3.6% of all treated patients) were
      symptomatic ICHs. Using HBC, 55 additional ICHs could be categorized. Of these
      total 156 ICHs, 29 (18.6%; 3.8% of all treated patients) were classified as
      symptomatic according to HBC. CONCLUSIONS: Classification of ICH by ECASS III and
      HBC criteria show distinct differences. These differences warrant special
      attention during interpretation and comparison of scientific publications.

PMID- 28455321
TI  - Nonprocedural Symptomatic Infarction and In-Stent Restenosis After Intracranial
      Angioplasty and Stenting in the SAMMPRIS Trial (Stenting and Aggressive Medical
      Management for the Prevention of Recurrent Stroke in Intracranial Stenosis).
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the
      frequency of symptomatic in-stent restenosis (ISR) and its contribution to
      nonprocedural symptomatic infarction in the SAMMPRIS trial (Stenting and
      Aggressive Medical Management for the Prevention of Recurrent Stroke in
      Intracranial Stenosis). METHODS: Patients without a periprocedural primary end
      point were followed up to determine the occurrence of any of the following
      events: ischemic stroke, cerebral infarct with temporary signs, or transient
      ischemic attack in the territory of the stented artery. Vascular imaging
      performed after these events was reviewed for ISR. Annual rates for symptomatic
      ISR were calculated using Kaplan-Meier estimates. RESULTS: Of 183 patients in the
      stenting group without a periprocedural primary end point, 27 (14.8%) had a
      symptomatic infarction (stroke or cerebral infarct with temporary signs) and 16
      (8.7%) had transient ischemic attack alone in the territory during a median
      follow-up of 35.0 months. Of the 27 patients with infarctions, 17 (9.3%) had an
      ischemic stroke and 10 (5.5%) had a cerebral infarct with temporary signs alone.
      Adequate vascular imaging to evaluate ISR was available in 24 patients with
      infarctions (showing ISR in 16 [66.7%]) and in 10 patients with transient
      ischemic attack alone (showing ISR in 8 [80%]). The 1-, 2-, and 3-year rates
      (with 95% confidence limits) for symptomatic ISR in the SAMMPRIS stent cohort
      were 9.6% (6.1%-14.9%), 11.3% (7.5%-17.0%), and 14.0% (9.6%-20.2%), respectively.
      CONCLUSIONS: Symptomatic ISR occurred in at least 1 of 7 patients in SAMMPRIS by
      3 years of follow-up and was likely responsible for the majority of nonprocedural
      cerebral infarctions. CLINICAL TRIAL REGISTRATION: URL:
      https://clinicaltrials.gov. Unique identifier: NCT00576693.

PMID- 28455323
TI  - Response by Grossberg et al to Letter Regarding Article, "Cervical Carotid Pseudo
      Occlusions and False Dissections: Intracranial Occlusions Masquerading as
      Extracranial Occlusions".

PMID- 28455324
TI  - Long-Term Exposure to Ambient Air Pollution and Subclinical Cerebrovascular
      Disease in NOMAS (the Northern Manhattan Study).
AB  - BACKGROUND AND PURPOSE: Long-term exposure to ambient air pollution is associated
      with higher risk of cardiovascular disease and stroke. We hypothesized that long
      term exposure to air pollution would be associated with magnetic resonance
      imaging markers of subclinical cerebrovascular disease. METHODS: Participants
      were 1075 stroke-free individuals aged >=50 years drawn from the magnetic
      resonance imaging subcohort of the Northern Manhattan Study who had lived at the
      same residence for at least 2 years before magnetic resonance imaging. Cross
      sectional associations between ambient air pollution and subclinical
      cerebrovascular disease were analyzed. RESULTS: We found an association between
      distance to roadway, a proxy for residential exposure to traffic pollution, and
      white matter hyperintensity volume; however, after adjusting for risk factors,
      this relationship was no longer present. All other associations between pollutant
      measures and white matter hyperintensity volume were null. There was no clear
      association between exposure to air pollutants and subclinical brain infarcts or
      total cerebral brain volume. CONCLUSIONS: We found no evidence that long-term
      exposure to ambient air pollution is independently associated with subclinical
      cerebrovascular disease in an urban population-based cohort.

PMID- 28455325
TI  - Letter by Ng et al Regarding Article, "Cervical Carotid Pseudo-Occlusions and
      False Dissections: Intracranial Occlusions Masquerading as Extracranial
      Occlusions".

PMID- 28455326
TI  - Acupuncture Therapy and Incidence of Depression After Stroke.
AB  - BACKGROUND AND PURPOSE: We investigated whether use of acupuncture within a 3
      month poststroke period after hospital discharge is associated with reduced risk
      of depression. METHODS: This cohort study included 16 046 patients aged >=18
      years with an initial hospitalization for stroke during 2000 and 2012 in the
      claims database of a universal health insurance program. Patients who had
      received acupuncture therapies within 3 months of discharge were defined as
      acupuncture users (n=1714). All patients were followed up for incidence of
      depression until the end of 2013. We assessed the association between use of
      acupuncture and incidence of depression using Cox proportional hazards models in
      all subjects and in propensity score-matched samples consisting of 1714 pairs of
      users and nonusers. RESULTS: During the follow-up period, the incidence of
      depression per 1000 person-years was 11.1 and 9.7 in users and nonusers,
      respectively. Neither multivariable-adjusted Cox models (hazard ratio, 1.04; 95%
      confidence interval, 0.84-1.29) nor the propensity score-matching model (hazard
      ratio, 1.06; 95% confidence interval, 0.79-1.42) revealed an association between
      use of acupuncture and incidence of depression. CONCLUSIONS: In patients admitted
      to hospital for stroke, acupuncture therapy within 3 months after discharge was
      not associated with subsequent incidence of depression.

PMID- 28455327
TI  - Novel Method for Reliable Identification of Siccibacter and Franconibacter
      Strains: from "Pseudo-Cronobacter" to New Enterobacteriaceae Genera.
AB  - In the last decade, strains of the genera Franconibacter and Siccibacter have
      been misclassified as first Enterobacter and later Cronobacter Because
      Cronobacter is a serious foodborne pathogen that affects premature neonates and
      elderly individuals, such misidentification may not only falsify epidemiological
      statistics but also lead to tests of powdered infant formula or other foods
      giving false results. Currently, the main ways of identifying Franconibacter and
      Siccibacter strains are by biochemical testing or by sequencing of the fusA gene
      as part of Cronobacter multilocus sequence typing (MLST), but in relation to
      these strains the former is generally highly difficult and unreliable while the
      latter remains expensive. To address this, we developed a fast, simple, and most
      importantly, reliable method for Franconibacter and Siccibacter identification
      based on intact-cell matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI-TOF MS). Our method integrates the following steps: data
      preprocessing using mMass software; principal-component analysis (PCA) for the
      selection of mass spectrum fingerprints of Franconibacter and Siccibacter
      strains; optimization of the Biotyper database settings for the creation of main
      spectrum projections (MSPs). This methodology enabled us to create an in-house
      MALDI MS database that extends the current MALDI Biotyper database by including
      Franconibacter and Siccibacter strains. Finally, we verified our approach using
      seven previously unclassified strains, all of which were correctly identified,
      thereby validating our method.IMPORTANCE We show that the majority of methods
      currently used for the identification of Franconibacter and Siccibacter bacteria
      are not able to properly distinguish these strains from those of Cronobacter
      While sequencing of the fusA gene as part of Cronobacter MLST remains the most
      reliable such method, it is highly expensive and time-consuming. Here, we
      demonstrate a cost-effective and reliable alternative that correctly
      distinguishes between Franconibacter, Siccibacter, and Cronobacter bacteria and
      identifies Franconibacter and Siccibacter at the species level. Using intact-cell
      MALDI-TOF MS, we extend the current MALDI Biotyper database with 11
      Franconibacter and Siccibacter MSPs. In addition, the use of our approach is
      likely to lead to a more reliable identification scheme for Franconibacter and
      Siccibacter strains and, consequently, a more trustworthy epidemiological picture
      of their involvement in disease.

PMID- 28455328
TI  - Coxiella burnetii Circulation in a Naturally Infected Flock of Sheep: Individual
      Follow-Up of Antibodies in Serum and Milk.
AB  - The control of Q fever, a zoonotic disease caused by the Coxiella burnetii
      bacterium, remains a scientific challenge. Domestic ruminants are considered the
      main reservoir, shedding C. burnetii essentially through parturition products
      during abortion or birth. Sheep are particularly frequently associated with human
      outbreaks, but there are insufficient field data to fully understand disease
      dynamics and to instigate efficient control measures. A longitudinal follow-up
      study of a naturally infected sheep flock was performed (i) to investigate
      relationships between seropositivity and bacterial shedding in the vaginal mucus,
      (ii) to describe the kinetics of antibodies, including responses to vaccination,
      (iii) to monitor maternal antibodies in ewe lambs, and (iv) to compare
      serological results for milk and serum samples. For 8 months, we collected blood
      samples every 3 weeks from 11 aborting and 26 nonaborting dairy ewes, 20
      nonaborting suckler ewes, and 9 ewe lambs. Individual milk samples were also
      obtained from lactating females. All serum and milk samples were tested by enzyme
      linked immunosorbent assay (ELISA), whereas vaginal swabs were tested by
      quantitative PCR. We found that some dairy females did not seroconvert despite
      shedding C. burnetii in their vaginal mucus. Overall, antibody levels in adult
      females were found to remain stable over time, with exceptions during the mating
      and lambing periods. Maternal antibodies decreased during the first month after
      birth. Interestingly, antibody levels in milk were correlated with those in
      serum. This study provides valuable field data that will help improve Q fever
      surveillance and within-flock management measures.IMPORTANCE Field data are
      necessary to improve the surveillance, diagnosis, and sanitary management of Q
      fever in livestock. Here, we provide extensive serological data obtained from
      serum and milk samples from infected and vaccinated ewes belonging to a naturally
      infected flock of sheep. We show that antibody levels are stable over time and
      seropositivity and vaginal shedding are not clearly correlated, whereas antibody
      levels in milk are strongly correlated with those in serum. Accordingly, we find
      that antibody levels in bulk tank milk are consistent with the variations
      observed in the serum of dairy females over time. We report the existence of
      maternal antibody transmission to ewe lambs and we show that the presence of
      maternal antibodies at birth does not prevent the development of a serological
      response to vaccination at the age of 4 months. Finally, we report that adult
      ewes generally seroconvert after vaccination, including during pregnancy.

PMID- 28455329
TI  - Rational Engineering of a Cold-Adapted alpha-Amylase from the Antarctic Ciliate
      Euplotes focardii for Simultaneous Improvement of Thermostability and Catalytic
      Activity.
AB  - The alpha-amylases are endo-acting enzymes that hydrolyze starch by randomly
      cleaving the 1,4-alpha-d-glucosidic linkages between the adjacent glucose units
      in a linear amylose chain. They have significant advantages in a wide range of
      applications, particularly in the food industry. The eukaryotic alpha-amylase
      isolated from the Antarctic ciliated protozoon Euplotes focardii (EfAmy) is an
      alkaline enzyme, different from most of the alpha-amylases characterized so far.
      Furthermore, EfAmy has the characteristics of a psychrophilic alpha-amylase, such
      as the highest hydrolytic activity at a low temperature and high thermolability,
      which is the major drawback of cold-active enzymes in industrial applications. In
      this work, we applied site-directed mutagenesis combined with rational design to
      generate a cold-active EfAmy with improved thermostability and catalytic
      efficiency at low temperatures. We engineered two EfAmy mutants. In one mutant,
      we introduced Pro residues on the A and B domains in surface loops. In the second
      mutant, we changed Val residues to Thr close to the catalytic site. The aim of
      these substitutions was to rigidify the molecular structure of the enzyme.
      Furthermore, we also analyzed mutants containing these combined substitutions.
      Biochemical enzymatic assays of engineered versions of EfAmy revealed that the
      combination of mutations at the surface loops increased the thermostability and
      catalytic efficiency of the enzyme. The possible mechanisms responsible for the
      changes in the biochemical properties are discussed by analyzing the three
      dimensional structural model.IMPORTANCE Cold-adapted enzymes have high specific
      activity at low and moderate temperatures, a property that can be extremely
      useful in various applications as it implies a reduction in energy consumption
      during the catalyzed reaction. However, the concurrent high thermolability of
      cold-adapted enzymes often limits their applications in industrial processes. The
      alpha-amylase from the psychrophilic Antarctic ciliate Euplotes focardii (named
      EfAmy) is a cold-adapted enzyme with optimal catalytic activity in an alkaline
      environment. These unique features distinguish it from most alpha-amylases
      characterized so far. In this work, we engineered a novel EfAmy with improved
      thermostability, substrate binding affinity, and catalytic efficiency to various
      extents, without impacting its pH preference. These characteristics can be
      considered important properties for use in the food, detergent, and textile
      industries and in other industrial applications. The enzyme engineering strategy
      developed in this study may also provide useful knowledge for future optimization
      of molecules to be used in particular industrial applications.

PMID- 28455330
TI  - Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by
      Arginine and Glucose in Clostridium botulinum ATCC 3502.
AB  - Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most
      potent biological toxin known and the causative agent of the paralytic disease
      botulism. The nutritional, environmental, and genetic regulation of BoNT
      synthesis, activation, stability, and toxin complex (TC) formation is not well
      studied. Previous studies indicated that growth and BoNT formation were affected
      by arginine and glucose in Clostridium botulinum types A and B. In the present
      study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with
      different levels of arginine and glucose and of three products of arginine
      metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth
      (optical density at 600 nm [OD600]), spore formation, and BoNT and TC formation
      by Western blotting and immunoprecipitation and for BoNT activity by mouse
      bioassay. A high level of arginine (20 g/liter) repressed BoNT production
      approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore
      production by greater than 1,000-fold. Similar effects on toxin production were
      seen with equivalent levels of citrulline but not ornithine or proline. In TPM
      lacking glucose, levels of formation of BoNT/A1 and TC were significantly
      decreased, and extracellular BoNT and TC proteins were partially inactivated
      after the first day of culture. An understanding of the regulation of C.
      botulinum growth and BoNT and TC formation should be valuable in defining
      requirements for BoNT formation in foods and clinical samples, improving the
      quality of BoNT for pharmaceutical preparations, and elucidating the biological
      functions of BoNTs for the bacterium.IMPORTANCE Botulinum neurotoxin (BoNT) is a
      major food safety and bioterrorism concern and is also an important
      pharmaceutical, and yet the regulation of its synthesis, activation, and
      stability in culture media, foods, and clinical samples is not well understood.
      This paper provides insights into the effects of critical nutrients on growth,
      lysis, spore formation, BoNT and TC production, and stability of BoNTs of C.
      botulinum We show that for C. botulinum ATCC 3502 cultured in a complex medium, a
      high level of arginine repressed BoNT expression by ca. 1,000-fold and also
      strongly reduced sporulation. Arginine stimulated growth and compensated for a
      lack of glucose. BoNT and toxin complex proteins were partially inactivated in a
      complex medium lacking glucose. This work should aid in optimizing BoNT
      production for pharmaceutical uses, and furthermore, an understanding of the
      nutritional regulation of growth and BoNT formation may provide insights into
      growth and BoNT formation in foods and clinical samples and into the enigmatic
      function of BoNTs in nature.

PMID- 28455331
TI  - Approaches for Reverse Line Blot-Based Detection of Microbial Pathogens in Ixodes
      ricinus Ticks Collected in Austria and Impact of the Chosen Method.
AB  - Ticks transmit a large number of pathogens capable of causing human disease. In
      this study, the PCR-reverse line blot (RLB) method was used to screen for
      pathogens in a total of 554 Ixodes ricinus ticks collected from all provinces of
      Austria. These pathogens belong to the genera Borrelia, Rickettsiae,
      Anaplasma/Ehrlichia (including "Candidatus Neoehrlichia"), Babesia, and Coxiella
      The pathogens with the highest detected prevalence were spirochetes of the
      Borrelia burgdorferisensu lato complex, in 142 ticks (25.6%). Borrelia afzelii
      (80/142) was the most frequently detected species, followed by Borrelia
      burgdorferisensu stricto (38/142) and Borrelia valaisiana (36/142). Borrelia
      garinii/Borrelia bavariensis, Borrelia lusitaniae, and Borrelia spielmanii were
      found in 28 ticks, 5 ticks, and 1 tick, respectively. Rickettsia spp. were
      detected in 93 ticks (16.8%): R. helvetica (39/93), R. raoultii (38/93), R.
      monacensis (2/93), and R. slovaca (1/93). Thirteen Rickettsia samples remain
      uncharacterized. "Candidatus Neoehrlichia mikurensis," Babesia spp. (B.
      venatorum, B. divergens, B. microti), and Anaplasma phagocytophilum were found in
      4.5%, 2.7%, and 0.7%, respectively. Coxiella burnetii was not detected. Multiple
      microorganisms were detected in 40 ticks (7.2%), and the cooccurrence of Babesia
      spp. and "Candidatus Neoehrlichia mikurensis" showed a significant positive
      correlation. We also compared different PCR-RLBs for detection of Borrelia
      burgdorferisensu lato and Rickettsia spp. and showed that different detection
      approaches provide highly diverse results, indicating that analysis of
      environmental samples remains challenging.IMPORTANCE This study determined the
      wide spectrum of tick-borne bacterial and protozoal pathogens that can be
      encountered in Austria. Surveillance of (putative) pathogenic microorganisms
      occurring in the environment is of medical importance, especially when those
      agents can be transmitted by ticks and cause disease. The observation of
      significant coinfections of certain microorganisms in field-collected ticks is an
      initial step to an improved understanding of microbial interactions in ticks. In
      addition, we show that variations in molecular detection methods, such as in
      primer pairs and target genes, can considerably influence the final results. For
      instance, detection of certain genospecies of borreliae may be better or worse by
      one method or the other, a fact of great importance for future screening studies.

PMID- 28455332
TI  - Absence of ppGpp Leads to Increased Mobilization of Intermediately Accumulated
      Poly(3-Hydroxybutyrate) in Ralstonia eutropha H16.
AB  - In this study, we constructed a set of Ralstonia eutropha H16 strains with
      single, double, or triple deletions of the (p)ppGpp synthase/hydrolase (spoT1),
      (p)ppGpp synthase (spoT2), and/or polyhydroxybutyrate (PHB) depolymerase (phaZa1
      or phaZa3) gene, and we determined the impact on the levels of (p)ppGpp and on
      accumulated PHB. Mutants with deletions of both the spoT1 and spoT2 genes were
      unable to synthesize detectable amounts of (p)ppGpp and accumulated only minor
      amounts of PHB, due to PhaZa1-mediated depolymerization of PHB. In contrast,
      unusually high levels of PHB were found in strains in which the (p)ppGpp
      concentration was increased by the overexpression of (p)ppGpp synthase (SpoT2)
      and the absence of (p)ppGpp hydrolase. Determination of (p)ppGpp levels in wild
      type R. eutropha under different growth conditions and induction of the stringent
      response by amino acid analogs showed that the concentrations of (p)ppGpp during
      the growth phase determine the amount of PHB remaining in later growth phases by
      influencing the efficiency of the PHB mobilization system in stationary growth.
      The data reported for a previously constructed DeltaspoT2 strain (C. J. Brigham,
      D. R. Speth, C. Rha, and A. J. Sinskey, Appl Environ Microbiol 78:8033-8044,
      2012, https://doi.org/10.1128/AEM.01693-12) were identified as due to an
      experimental error in strain construction, and our results are in contrast to the
      previous indication that the spoT2 gene product is essential for PHB accumulation
      in R. eutrophaIMPORTANCE Polyhydroxybutyrate (PHB) is an important intracellular
      carbon and energy storage compound in many prokaryotes and helps cells survive
      periods of starvation and other stress conditions. Research activities in several
      laboratories over the past 3 decades have shown that both PHB synthase and PHB
      depolymerase are constitutively expressed in most PHB-accumulating bacteria, such
      as Ralstonia eutropha This implies that PHB synthase and depolymerase activities
      must be well regulated in order to avoid a futile cycle of simultaneous PHB
      synthesis and PHB degradation (mobilization). Previous reports suggested that the
      stringent response in Rhizobium etli and R. eutropha is involved in the
      regulation of PHB metabolism. However, the levels of (p)ppGpp and the influence
      of those levels on PHB accumulation and PHB mobilization have not yet been
      determined for any PHB-accumulating species. In this study, we optimized a
      (p)ppGpp extraction procedure and a high-performance liquid chromatography-mass
      spectrometry (HPLC-MS)-based detection method for the quantification of (p)ppGpp
      in R. eutropha This enabled us to study the relationship between the
      concentrations of (p)ppGpp and the accumulated levels of PHB in the wild type and
      in several constructed mutant strains. We show that overproduction of the
      alarmone (p)ppGpp correlated with reduced growth and massive overproduction of
      PHB. In contrast, in the absence of (p)ppGpp, mobilization of PHB was
      dramatically enhanced.

PMID- 28455333
TI  - A Novel Quorum-Quenching N-Acylhomoserine Lactone Acylase from Acidovorax sp.
      Strain MR-S7 Mediates Antibiotic Resistance.
AB  - N-Acylhomoserine lactone acylase (AHL acylase) is a well-known enzyme responsible
      for disrupting cell-cell communication (quorum sensing) in bacteria. Here, we
      isolated and characterized a novel and unique AHL acylase (designated MacQ) from
      a multidrug-resistant bacterium, Acidovorax sp. strain MR-S7. The purified MacQ
      protein heterologously expressed in Escherichia coli degraded a wide variety of
      AHLs, ranging from C6 to C14 side chains with or without 3-oxo substitutions. We
      also observed that AHL-mediated virulence factor production in a plant pathogen,
      Pectobacterium carotovorum, was dramatically attenuated by coculture with MacQ
      overexpressing Escherichia coli, whereas E. coli with an empty vector was unable
      to quench the pathogenicity, which strongly indicates that MacQ can act in vivo
      as a quorum-quenching enzyme and interfere with the quorum-sensing system in the
      pathogen. In addition, this enzyme was found to be capable of degrading a wide
      spectrum of beta-lactams (penicillin G, ampicillin, amoxicillin, carbenicillin,
      cephalexin, and cefadroxil) by deacylation, clearly indicating that MacQ is a
      bifunctional enzyme that confers both quorum quenching and antibiotic resistance
      on strain MR-S7. MacQ has relatively low amino acid sequence identity to any of
      the known acylases (<39%) and has among the broadest substrate range. Our
      findings provide the possibility that AHL acylase genes can be an alternative
      source of antibiotic resistance genes posing a threat to human health if they
      migrate and transfer to pathogenic bacteria.IMPORTANCEN-Acylhomoserine lactones
      (AHLs) are well-known signal molecules for bacterial cell-cell communication
      (quorum sensing), and AHL acylase, which is able to degrade AHLs, has been
      recognized as a major target for quorum-sensing interference (quorum quenching)
      in pathogens. In this work, we succeeded in isolating a novel AHL acylase (MacQ)
      from a multidrug-resistant bacterium and demonstrated that the MacQ enzyme could
      confer multidrug resistance as well as quorum quenching on the host organism.
      Indeed, the purified MacQ protein was found to be bifunctional and capable of
      degrading not only various AHL derivatives but also multiple beta-lactam
      antibiotics by deacylation activities. Although quorum quenching and antibiotic
      resistance have been recognized to be distinct biological functions, our findings
      clearly link the two functions by discovering the novel bifunctional enzyme and
      further providing the possibility that a hitherto-overlooked antibiotic
      resistance mechanism mediated by the quorum-quenching enzyme may exist in natural
      environments and perhaps in clinical settings.

PMID- 28455334
TI  - Validation of the Hirst-Type Spore Trap for Simultaneous Monitoring of
      Prokaryotic and Eukaryotic Biodiversities in Urban Air Samples by Next-Generation
      Sequencing.
AB  - Pollen, fungi, and bacteria are the main microscopic biological entities present
      in outdoor air, causing allergy symptoms and disease transmission and having a
      significant role in atmosphere dynamics. Despite their relevance, a method for
      monitoring simultaneously these biological particles in metropolitan environments
      has not yet been developed. Here, we assessed the use of the Hirst-type spore
      trap to characterize the global airborne biota by high-throughput DNA sequencing,
      selecting regions of the 16S rRNA gene and internal transcribed spacer for the
      taxonomic assignment. We showed that aerobiological communities are well
      represented by this approach. The operational taxonomic units (OTUs) of two traps
      working synchronically compiled >87% of the total relative abundance for
      bacterial diversity collected in each sampler, >89% for fungi, and >97% for
      pollen. We found a good correspondence between traditional characterization by
      microscopy and genetic identification, obtaining more-accurate taxonomic
      assignments and detecting a greater diversity using the latter. We also
      demonstrated that DNA sequencing accurately detects differences in biodiversity
      between samples. We concluded that high-throughput DNA sequencing applied to
      aerobiological samples obtained with Hirst spore traps provides reliable results
      and can be easily implemented for monitoring prokaryotic and eukaryotic entities
      present in the air of urban areas.IMPORTANCE Detection, monitoring, and
      characterization of the wide diversity of biological entities present in the air
      are difficult tasks that require time and expertise in different disciplines. We
      have evaluated the use of the Hirst spore trap (an instrument broadly employed in
      aerobiological studies) to detect and identify these organisms by DNA-based
      analyses. Our results showed a consistent collection of DNA and a good
      concordance with traditional methods for identification, suggesting that these
      devices can be used as a tool for continuous monitoring of the airborne
      biodiversity, improving taxonomic resolution and characterization together. They
      are also suitable for acquiring novel DNA amplicon-based information in order to
      gain a better understanding of the biological particles present in a scarcely
      known environment such as the air.

PMID- 28455335
TI  - Yersinia pestis Resists Predation by Acanthamoeba castellanii and Exhibits
      Prolonged Intracellular Survival.
AB  - Plague is a flea-borne rodent-associated zoonotic disease caused by Yersinia
      pestis The disease is characterized by epizootics with high rodent mortalities,
      punctuated by interepizootic periods when the bacterium persists in an unknown
      reservoir. This study investigates the interaction between Y. pestis and the
      ubiquitous soil free-living amoeba (FLA) Acanthamoeba castellanii to assess if
      the bacterium can survive within soil amoebae and whether intracellular
      mechanisms are conserved between infection of mammalian macrophages and soil
      amoebae. The results demonstrate that during coculture with amoebae,
      representative Y. pestis strains of epidemic biovars Medievalis, Orientalis, and
      Antiqua are phagocytized and able to survive within amoebae for at least 5 days.
      Key Y. pestis determinants of the intracellular interaction of Y. pestis and
      phagocytic macrophages, PhoP and the type three secretion system (T3SS), were
      then tested for their roles in the Y. pestis-amoeba interaction. Consistent with
      a requirement for the PhoP transcriptional activator in the intracellular
      survival of Y. pestis in macrophages, a PhoP mutant is unable to survive when
      cocultured with amoebae. Additionally, induction of the T3SS blocks phagocytic
      uptake of Y. pestis by amoebae, similar to that which occurs during macrophage
      infection. Electron microscopy revealed that in A. castellanii, Y. pestis resides
      intact within spacious vacuoles which were characterized using lysosomal trackers
      as being separated from the lysosomal compartment. This evidence for prolonged
      survival and subversion of intracellular digestion of Y. pestis within FLA
      suggests that protozoa may serve as a protective soil reservoir for Y.
      pestisIMPORTANCEYersinia pestis is a reemerging flea-borne zoonotic disease.
      Sylvatic plague cycles are characterized by an epizootic period during which the
      disease spreads rapidly, causing high rodent mortality, and an interepizootic
      period when the bacterium quiescently persists in an unknown reservoir. An
      understanding of the ecology of Y. pestis in the context of its persistence in
      the environment and its reactivation to initiate a new epizootic cycle is key to
      implementing novel surveillance strategies to more effectively predict and
      prevent new disease outbreaks. Here, we demonstrate prolonged survival and
      subversion of intracellular digestion of Y. pestis within a soil free-living
      amoeba. This suggests the potential role for protozoa as a protective soil
      reservoir for Y. pestis, which may help explain the recrudescence of plague
      epizootics.

PMID- 28455336
TI  - Insights into Nitrate-Reducing Fe(II) Oxidation Mechanisms through Analysis of
      Cell-Mineral Associations, Cell Encrustation, and Mineralogy in the
      Chemolithoautotrophic Enrichment Culture KS.
AB  - Most described nitrate-reducing Fe(II)-oxidizing bacteria (NRFeOB) are
      mixotrophic and depend on organic cosubstrates for growth. Encrustation of cells
      in Fe(III) minerals has been observed for mixotrophic NRFeOB but not for
      autotrophic phototrophic and microaerophilic Fe(II) oxidizers. So far, little is
      known about cell-mineral associations in the few existing autotrophic NRFeOB.
      Here, we investigate whether the designated autotrophic Fe(II)-oxidizing strain
      (closely related to Gallionella and Sideroxydans) or the heterotrophic nitrate
      reducers that are present in the autotrophic nitrate-reducing Fe(II)-oxidizing
      enrichment culture KS form mineral crusts during Fe(II) oxidation under
      autotrophic and mixotrophic conditions. In the mixed culture, we found no
      significant encrustation of any of the cells both during autotrophic oxidation of
      8 to 10 mM Fe(II) coupled to nitrate reduction and during cultivation under
      mixotrophic conditions with 8 to 10 mM Fe(II), 5 mM acetate, and 4 mM nitrate,
      where higher numbers of heterotrophic nitrate reducers were present. Two pure
      cultures of heterotrophic nitrate reducers (Nocardioides and Rhodanobacter)
      isolated from culture KS were analyzed under mixotrophic growth conditions. We
      found green rust formation, no cell encrustation, and only a few mineral
      particles on some cell surfaces with 5 mM Fe(II) and some encrustation with 10 mM
      Fe(II). Our findings suggest that enzymatic, autotrophic Fe(II) oxidation coupled
      to nitrate reduction forms poorly crystalline Fe(III) oxyhydroxides and proceeds
      without cellular encrustation while indirect Fe(II) oxidation via heterotrophic
      nitrate-reduction-derived nitrite can lead to green rust as an intermediate
      mineral and significant cell encrustation. The extent of encrustation caused by
      indirect Fe(II) oxidation by reactive nitrogen species depends on Fe(II)
      concentrations and is probably negligible under environmental conditions in most
      habitats.IMPORTANCE Most described nitrate-reducing Fe(II)-oxidizing bacteria
      (NRFeOB) are mixotrophic (their growth depends on organic cosubstrates) and can
      become encrusted in Fe(III) minerals. Encrustation is expected to be harmful and
      poses a threat to cells if it also occurs under environmentally relevant
      conditions. Nitrite produced during heterotrophic denitrification reacts with
      Fe(II) abiotically and is probably the reason for encrustation in mixotrophic
      NRFeOB. Little is known about cell-mineral associations in autotrophic NRFeOB
      such as the enrichment culture KS. Here, we show that no encrustation occurs in
      culture KS under autotrophic and mixotrophic conditions while heterotrophic
      nitrate-reducing isolates from culture KS become encrusted. These findings
      support the hypothesis that encrustation in mixotrophic cultures is caused by the
      abiotic reaction of Fe(II) with nitrite and provide evidence that Fe(II)
      oxidation in culture KS is enzymatic. Furthermore, we show that the extent of
      encrustation caused by indirect Fe(II) oxidation by reactive nitrogen species
      depends on Fe(II) concentrations and is probably negligible in most environmental
      habitats.

PMID- 28455337
TI  - Laboratory Evolution to Alternating Substrate Environments Yields Distinct
      Phenotypic and Genetic Adaptive Strategies.
AB  - Adaptive laboratory evolution (ALE) experiments are often designed to maintain a
      static culturing environment to minimize confounding variables that could
      influence the adaptive process, but dynamic nutrient conditions occur frequently
      in natural and bioprocessing settings. To study the nature of carbon substrate
      fitness tradeoffs, we evolved batch cultures of Escherichia coli via serial
      propagation into tubes alternating between glucose and either xylose, glycerol,
      or acetate. Genome sequencing of evolved cultures revealed several genetic
      changes preferentially selected for under dynamic conditions and different
      adaptation strategies depending on the substrates being switched between; in some
      environments, a persistent "generalist" strain developed, while in another, two
      "specialist" subpopulations arose that alternated dominance. Diauxic lag
      phenotype varied across the generalists and specialists, in one case being
      completely abolished, while gene expression data distinguished the
      transcriptional strategies implemented by strains in pursuit of growth
      optimality. Genome-scale metabolic modeling techniques were then used to help
      explain the inherent substrate differences giving rise to the observed distinct
      adaptive strategies. This study gives insight into the population dynamics of
      adaptation in an alternating environment and into the underlying metabolic and
      genetic mechanisms. Furthermore, ALE-generated optimized strains have phenotypes
      with potential industrial bioprocessing applications.IMPORTANCE Evolution and
      natural selection inexorably lead to an organism's improved fitness in a given
      environment, whether in a laboratory or natural setting. However, despite the
      frequent natural occurrence of complex and dynamic growth environments,
      laboratory evolution experiments typically maintain simple, static culturing
      environments so as to reduce selection pressure complexity. In this study, we
      investigated the adaptive strategies underlying evolution to fluctuating
      environments by evolving Escherichia coli to conditions of frequently switching
      growth substrate. Characterization of evolved strains via a number of different
      data types revealed the various genetic and phenotypic changes implemented in
      pursuit of growth optimality and how these differed across the different growth
      substrates and switching protocols. This work not only helps to establish general
      principles of adaptation to complex environments but also suggests strategies for
      experimental design to achieve desired evolutionary outcomes.

PMID- 28455338
TI  - Enzymes Required for Maltodextrin Catabolism in Enterococcus faecalis Exhibit
      Novel Activities.
AB  - Maltose and maltodextrins are formed during the degradation of starch or
      glycogen. Maltodextrins are composed of a mixture of maltooligosaccharides formed
      by alpha-1,4- but also some alpha-1,6-linked glucosyl residues. The alpha-1,6
      linked glucosyl residues are derived from branching points in the
      polysaccharides. In Enterococcus faecalis, maltotriose is mainly transported and
      phosphorylated by a phosphoenolpyruvate:carbohydrate phosphotransferase system.
      The formed maltotriose-6"-phosphate is intracellularly dephosphorylated by a
      specific phosphatase, MapP. In contrast, maltotetraose and longer
      maltooligosaccharides up to maltoheptaose are taken up without phosphorylation
      via the ATP binding cassette transporter MdxEFG-MsmX. We show that the maltose
      producing maltodextrin hydrolase MmdH (GenBank accession no. EFT41964) in strain
      JH2-2 catalyzes the first catabolic step of alpha-1,4-linked
      maltooligosaccharides. The purified enzyme converts even-numbered alpha-1,4
      linked maltooligosaccharides (maltotetraose, etc.) into maltose and odd-numbered
      (maltotriose, etc.) into maltose and glucose. Inactivation of mmdH therefore
      prevents the growth of E. faecalis on maltooligosaccharides ranging from
      maltotriose to maltoheptaose. Surprisingly, MmdH also functions as a maltogenic
      alpha-1,6-glucosidase, because it converts the maltotriose isomer isopanose into
      maltose and glucose. In addition, E. faecalis contains a glucose-producing alpha
      1,6-specific maltodextrin hydrolase (GenBank accession no. EFT41963, renamed
      GmdH). This enzyme converts panose, another maltotriose isomer, into glucose and
      maltose. A gmdH mutant had therefore lost the capacity to grow on panose. The
      genes mmdH and gmdH are organized in an operon together with GenBank accession
      no. EFT41962 (renamed mmgT). Purified MmgT transfers glucosyl residues from one
      alpha-1,4-linked maltooligosaccharide molecule to another. For example, it
      catalyzes the disproportionation of maltotriose by transferring a glucosyl
      residue to another maltotriose molecule, thereby forming maltotetraose and
      maltose together with a small amount of maltopentaose.IMPORTANCE The utilization
      of maltodextrins by Enterococcus faecalis has been shown to increase the
      virulence of this nosocomial pathogen. However, little is known about how this
      organism catabolizes maltodextrins. We identified two enzymes involved in the
      metabolism of various alpha-1,4- and alpha-1,6-linked maltooligosaccharides. We
      found that one of them functions as a maltose-producing alpha-glucosidase with
      relaxed linkage specificity (alpha-1,4 and alpha-1,6) and exo- and
      endoglucosidase activities. A third enzyme, which resembles amylomaltase,
      exclusively transfers glucosyl residues from one maltooligosaccharide molecule to
      another. Similar enzymes are present in numerous other Firmicutes, such as
      streptococci and lactobacilli, suggesting that these organisms follow the same
      maltose degradation pathway as E. faecalis.

PMID- 28455339
TI  - Improved alpha-Amylase Production by Dephosphorylation Mutation of CreD, an
      Arrestin-Like Protein Required for Glucose-Induced Endocytosis of Maltose
      Permease and Carbon Catabolite Derepression in Aspergillus oryzae.
AB  - Aspergillusoryzae produces copious amount of amylolytic enzymes, and MalP, a
      major maltose permease, is required for the expression of amylase-encoding genes.
      The expression of these genes is strongly repressed by carbon catabolite
      repression (CCR) in the presence of glucose. MalP is transported from the plasma
      membrane to the vacuole by endocytosis, which requires the homolog of E6-AP
      carboxyl terminus ubiquitin ligase HulA, an ortholog of yeast Rsp5. In yeast,
      arrestin-like proteins mediate endocytosis as adaptors of Rsp5 and transporters.
      In the present study, we examined the involvement of CreD, an arrestin-like
      protein, in glucose-induced MalP endocytosis and CCR of amylase-encoding genes.
      Deletion of creD inhibited the glucose-induced endocytosis of MalP, and CreD
      showed physical interaction with HulA. Phosphorylation of CreD was detected by
      Western blotting, and two serine residues were determined as the putative
      phosphorylation sites. However, the phosphorylation state of the serine residues
      did not regulate MalP endocytosis and its interaction with HulA. Although alpha
      amylase production was significantly repressed by creD deletion, both
      phosphorylation and dephosphorylation mimics of CreD had a negligible effect on
      alpha-amylase activity. Interestingly, dephosphorylation of CreD was required for
      CCR relief of amylase genes that was triggered by disruption of the
      deubiquitinating enzyme-encoding gene creB The alpha-amylase activity of the creB
      mutant was 1.6-fold higher than that of the wild type, and the dephosphorylation
      mimic of CreD further improved the alpha-amylase activity by 2.6-fold. These
      results indicate that a combination of the dephosphorylation mutation of CreD and
      creB disruption increased the production of amylolytic enzymes in A.
      oryzaeIMPORTANCE In eukaryotes, glucose induces carbon catabolite repression
      (CCR) and proteolytic degradation of plasma membrane transporters via
      endocytosis. Glucose-induced endocytosis of transporters is mediated by their
      ubiquitination, and arrestin-like proteins act as adaptors of transporters and
      ubiquitin ligases. In this study, we showed that CreD, an arrestin-like protein,
      is involved in glucose-induced endocytosis of maltose permease and carbon
      catabolite derepression of amylase gene expression in Aspergillusoryzae
      Dephosphorylation of CreD was required for CCR relief triggered by the disruption
      of creB, which encodes a deubiquitinating enzyme; a combination of the
      phosphorylation-defective mutation of CreD and creB disruption dramatically
      improved alpha-amylase production. This study shows the dual function of an
      arrestin-like protein and provides a novel approach for improving the production
      of amylolytic enzymes in A. oryzae.

PMID- 28455340
TI  - Engineering Escherichia coli Nicotinic Acid Mononucleotide Adenylyltransferase
      for Fully Active Amidated NAD Biosynthesis.
AB  - NAD and its reduced form NADH function as essential redox cofactors and have
      major roles in determining cellular metabolic features. NAD can be synthesized
      through the deamidated and amidated pathways, for which the key reaction involves
      adenylylation of nicotinic acid mononucleotide (NaMN) and nicotinamide
      mononucleotide (NMN), respectively. In Escherichia coli, NAD de novo biosynthesis
      depends on the protein NadD-catalyzed adenylylation of NaMN to nicotinic acid
      adenine dinucleotide (NaAD), followed by NAD synthase-catalyzed amidation. In
      this study, we engineered NadD to favor NMN for improved amidated pathway
      activity. We designed NadD mutant libraries, screened by a malic enzyme-coupled
      colorimetric assay, and identified two variants, 11B4 (Y84V/Y118D) and 16D8
      (A86W/Y118N), with a high preference for NMN. Whereas in the presence of NMN both
      variants were capable of enabling the viability of cells of E. coli BW25113
      derived NAD-auxotrophic strain YJE003, for which the last step of the deamidated
      pathway is blocked, the 16D8 expression strain could grow without exogenous NMN
      and accumulated a higher cellular NAD(H) level than BW25113 in the stationary
      phase. These mutants established fully active amidated NAD biosynthesis and
      offered a new opportunity to manipulate NAD metabolism for biocatalysis and
      metabolic engineering.IMPORTANCE Adenylylation of nicotinic acid mononucleotide
      (NaMN) and adenylylation of nicotinamide mononucleotide (NMN), respectively, are
      the key steps in the deamidated and amidated pathways for NAD biosynthesis. In
      most organisms, canonical NAD biosynthesis follows the deamidated pathway. Here
      we engineered Escherichia coli NaMN adenylyltransferase to favor NMN and
      expressed the mutant enzyme in an NAD-auxotrophic E. coli strain that has the
      last step of the deamidated pathway blocked. The engineered strain survived in M9
      medium, which indicated the implementation of a functional amidated pathway for
      NAD biosynthesis. These results enrich our understanding of NAD biosynthesis and
      are valuable for manipulation of NAD homeostasis for metabolic engineering.

PMID- 28455341
TI  - Lack of Methylated Hopanoids Renders the Cyanobacterium Nostoc punctiforme
      Sensitive to Osmotic and pH Stress.
AB  - To investigate the function of 2-methylhopanoids in modern cyanobacteria, the
      hpnP gene coding for the radical S-adenosyl methionine (SAM) methylase protein
      that acts on the C-2 position of hopanoids was deleted from the filamentous
      cyanobacterium Nostoc punctiforme ATCC 29133S. The resulting DeltahpnP mutant
      lacked all 2-methylhopanoids but was found to produce much higher levels of two
      bacteriohopanepentol isomers than the wild type. Growth rates of the DeltahpnP
      mutant cultures were not significantly different from those of the wild type
      under standard growth conditions. Akinete formation was also not impeded by the
      absence of 2-methylhopanoids. The relative abundances of the different hopanoid
      structures in akinete-dominated cultures of the wild-type and DeltahpnP mutant
      strains were similar to those of vegetative cell-dominated cultures. However, the
      DeltahpnP mutant was found to have decreased growth rates under both pH and
      osmotic stress, confirming a role for 2-methylhopanoids in stress tolerance.
      Evidence of elevated photosystem II yield and NAD(P)H-dependent oxidoreductase
      activity in the DeltahpnP mutant under stress conditions, compared to the wild
      type, suggested that the absence of 2-methylhopanoids increases cellular
      metabolic rates under stress conditions.IMPORTANCE As the first group of
      organisms to develop oxygenic photosynthesis, Cyanobacteria are central to the
      evolutionary history of life on Earth and the subsequent oxygenation of the
      atmosphere. To investigate the origin of cyanobacteria and the emergence of
      oxygenic photosynthesis, geobiologists use biomarkers, the remnants of lipids
      produced by different organisms that are found in geologic sediments. 2
      Methylhopanes have been considered indicative of cyanobacteria in some
      environmental settings, with the parent lipids 2-methylhopanoids being present in
      many contemporary cyanobacteria. We have created a Nostoc punctiforme DeltahpnP
      mutant strain that does not produce 2-methylhopanoids to assess the influence of
      2-methylhopanoids on stress tolerance. Increased metabolic activity in the mutant
      under stress indicates compensatory alterations in metabolism in the absence of 2
      methylhopanoids.

PMID- 28455343
TI  - 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the
      Management of Heart Failure: A Report of the American College of
      Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
      and the Heart Failure Society of America.

PMID- 28455344
TI  - Temporal Trends in Incidence, Prevalence, and Mortality of Atrial Fibrillation in
      Primary Care.
AB  - BACKGROUND: Incidence and prevalence of atrial fibrillation (AF) are expected to
      increase dramatically; however, we currently lack comprehensive data on temporal
      trends in unselected clinical populations. METHODS AND RESULTS: Analysis of the
      UK Clinical Practice Research Datalink (CPRD) from 1998 to 2010 of patients with
      incident AF, excluding major valvular disease, linked to hospital admission data
      and national statistics. Fifty-seven thousand eight hundred eighteen adults were
      identified with mean age 74.2 (SD, 11.7) years and 48.3% women. Overall age
      adjusted incidence of AF per 1000 person years was 1.11 (95% CI, 1.09-1.13) in
      1998-2001, 1.33 (1.31-1.34) in 2002-2006, and 1.33 (1.31-1.35) in 2007-2010.
      Ongoing increases in incidence were noted for patients aged >=75 years, with
      similar temporal patterns in women and men. Associated comorbidities varied over
      time, with a constant prevalence of previous stroke, increases in hypertension
      and diabetes mellitus, and decreases in ischemic heart disease. Among patients
      aged 55 to 74 years, there was a significant reduction in mortality over time
      (P<0.001), but mortality rates in patients aged >=75 years remained static at 14%
      to 15% per year (P=0.84). Projections of AF prevalence demonstrated a constant
      yearly rise, increasing from 700 000 patients in 2010 to between 1.3 and 1.8
      million patients with AF in the United Kingdom by 2060. CONCLUSIONS: In a large
      general practice population, incident AF increased and then plateaued overall,
      with a continued increase in patients aged >=75 years. The large projected
      increase in AF prevalence associated with temporal changes in AF-related
      comorbidities suggests the need for comprehensive implementation of AF prevention
      and management strategies.

PMID- 28455346
TI  - Mandatory reporting of fitness to drive doesn't work.

PMID- 28455345
TI  - Bilirubin Decreases Macrophage Cholesterol Efflux and ATP-Binding Cassette
      Transporter A1 Protein Expression.
AB  - BACKGROUND: Mild but chronically elevated circulating unconjugated bilirubin is
      associated with reduced total and low-density lipoprotein cholesterol
      concentration, which is associated with reduced cardiovascular disease risk. We
      aimed to investigate whether unconjugated bilirubin influences macrophage
      cholesterol efflux, as a potential mechanism for the altered circulating
      lipoprotein concentrations observed in hyperbilirubinemic individuals. METHODS
      AND RESULTS: Cholesterol efflux from THP-1 macrophages was assessed using plasma
      obtained from normo- and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per
      group) or (heterozygote/homozygote Gunn) rats (n=20 per group) as an acceptor.
      Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats
      induced significantly reduced cholesterol efflux compared with normobilirubinemic
      plasma. Unconjugated bilirubin (3-17.1 MUmol/L) exogenously added to plasma- or
      apolipoprotein A1-supplemented media also decreased macrophage cholesterol efflux
      in a concentration- and time-dependent manner. We also showed reduced protein
      expression of the ATP-binding cassette transporter A1 (ABCA1), a transmembrane
      cholesterol transporter involved in apolipoprotein A1-mediated cholesterol
      efflux, in THP-1 macrophages treated with unconjugated bilirubin and in
      peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals.
      Furthermore, we demonstrated that bilirubin accelerates the degradation rate of
      the ABCA1 protein in THP-1 macrophages. CONCLUSIONS: Cholesterol efflux from THP
      1 macrophages is decreased in the presence of plasma obtained from humans and
      rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on
      cholesterol efflux was demonstrated and is associated with decreased ABCA1
      protein expression. These data improve our knowledge concerning bilirubin's
      impact on cholesterol transport and represent an important advancement in our
      understanding of bilirubin's role in cardiovascular disease.

PMID- 28455347
TI  - Still no "credible plan" to increase GP numbers, say MPs.

PMID- 28455348
TI  - A spectrum of modularity in multi-functional gene circuits.
AB  - A major challenge in systems biology is to understand the relationship between a
      circuit's structure and its function, but how is this relationship affected if
      the circuit must perform multiple distinct functions within the same organism? In
      particular, to what extent do multi-functional circuits contain modules which
      reflect the different functions? Here, we computationally survey a range of bi
      functional circuits which show no simple structural modularity: They can switch
      between two qualitatively distinct functions, while both functions depend on all
      genes of the circuit. Our analysis reveals two distinct classes: hybrid circuits
      which overlay two simpler mono-functional sub-circuits within their circuitry,
      and emergent circuits, which do not. In this second class, the bi-functionality
      emerges from more complex designs which are not fully decomposable into distinct
      modules and are consequently less intuitive to predict or understand. These non
      intuitive emergent circuits are just as robust as their hybrid counterparts, and
      we therefore suggest that the common bias toward studying modular systems may
      hinder our understanding of real biological circuits.

PMID- 28455349
TI  - A Notch positive feedback in the intestinal stem cell niche is essential for stem
      cell self-renewal.
AB  - The intestinal epithelium is the fastest regenerative tissue in the body, fueled
      by fast-cycling stem cells. The number and identity of these dividing and
      migrating stem cells are maintained by a mosaic pattern at the base of the crypt.
      How the underlying regulatory scheme manages this dynamic stem cell niche is not
      entirely clear. We stimulated intestinal organoids with Notch ligands and
      inhibitors and discovered that intestinal stem cells employ a positive feedback
      mechanism via direct Notch binding to the second intron of the Notch1 gene.
      Inactivation of the positive feedback by CRISPR/Cas9 mutation of the binding
      sequence alters the mosaic stem cell niche pattern and hinders regeneration in
      organoids. Dynamical system analysis and agent-based multiscale stochastic
      modeling suggest that the positive feedback enhances the robustness of Notch
      mediated niche patterning. This study highlights the importance of feedback
      mechanisms in spatiotemporal control of the stem cell niche.

PMID- 28455350
TI  - The Genomic Architecture of Flowering Time Varies Across Space and Time in
      Mimulus guttatus.
AB  - The degree to which genomic architecture varies across space and time is central
      to the evolution of genomes in response to natural selection. Bulked-segregant
      mapping combined with pooled sequencing provides an efficient means to estimate
      the effect of genetic variants on quantitative traits. We develop a novel
      likelihood framework to identify segregating variation within multiple
      populations and generations while accommodating estimation error on a sample- and
      SNP-specific basis. We use this method to map loci for flowering time within
      natural populations of Mimulus guttatus, collecting the early- and late-flowering
      plants from each of three neighboring populations and two consecutive
      generations. Structural variants, such as inversions, and genes from multiple
      flowering-time pathways exhibit the strongest associations with flowering time.
      We find appreciable variation in genetic effects on flowering time across both
      time and space; the greatest differences evident between populations, where
      numerous factors (environmental variation, genomic background, and private
      polymorphisms) likely contribute to heterogeneity. However, the changes across
      years within populations clearly identify genotype-by-environment interactions as
      an important influence on flowering time variation.

PMID- 28455352
TI  - Correction for Xu et al., "Interaction of the Small GTPase Cdc42 with Arginine
      Kinase Restricts White Spot Syndrome Virus in Shrimp".

PMID- 28455353
TI  - Classic Spotlight, 1986 and 1987: Articles of Significant Interest Selected from
      the Journal of Virology Archives by the Editors.

PMID- 28455351
TI  - The Nucleoporin Nup2 Contains a Meiotic-Autonomous Region that Promotes the
      Dynamic Chromosome Events of Meiosis.
AB  - Meiosis is a specialized cellular program required to create haploid gametes from
      diploid parent cells. Homologous chromosomes pair, synapse, and recombine in a
      dynamic environment that accommodates gross chromosome reorganization and
      significant chromosome motion, which are critical for normal chromosome
      segregation. In Saccharomyces cerevisiae, Ndj1 is a meiotic telomere-associated
      protein required for physically attaching telomeres to proteins embedded in the
      nuclear envelope. In this study, we identified additional proteins that act at
      the nuclear periphery from meiotic cell extracts, including Nup2, a nonessential
      nucleoporin with a known role in tethering interstitial chromosomal loci to the
      nuclear pore complex. We found that deleting NUP2 affects meiotic progression and
      spore viability, and gives increased levels of recombination intermediates and
      products. We identified a previously uncharacterized 125 aa region of Nup2 that
      is necessary and sufficient for its meiotic function, thus behaving as a meiotic
      autonomous region (MAR). Nup2-MAR forms distinct foci on spread meiotic
      chromosomes, with a subset overlapping with Ndj1 foci. Localization of Nup2-MAR
      to meiotic chromosomes does not require Ndj1, nor does Ndj1 localization require
      Nup2, suggesting these proteins function in different pathways, and their
      interaction is weak or indirect. Instead, several severe synthetic phenotypes are
      associated with the nup2Delta ndj1Delta double mutant, including delayed turnover
      of recombination joint molecules, and a failure to undergo nuclear divisions
      without also arresting the meiotic program. These data suggest Nup2 and Ndj1
      support partially overlapping functions that promote two different levels of
      meiotic chromosome organization necessary to withstand a dynamic stage of the
      eukaryotic life cycle.

PMID- 28455354
TI  - Correction for Devhare et al., "Exosome-Mediated Intercellular Communication
      between Hepatitis C Virus-Infected Hepatocytes and Hepatic Stellate Cells".

PMID- 28455358
TI  - Erratum.

PMID- 28455357
TI  - Fission yeast neddylation ligase Dcn1 facilitates cohesin cleavage and chromosome
      segregation at anaphase.
AB  - Post-translational protein modification such as phosphorylation and
      ubiquitination are critical during mitosis to ensure proper timing and
      progression of chromosome segregation. It has been recently recognized that
      another type of protein modification - neddylation - may also regulate mitosis
      and chromosome segregation. The conserved protein DCN1 (defective cullin
      neddylation 1) has been shown, when knocked-down by RNAi, to result in
      multinucleated cells and/or blockage of cell proliferation. However, how DCN1
      functions in mitosis and chromosome segregation is not known. We report here the
      fission yeast dcn1+ and its role in mitosis and chromosome segregation. Dcn1-GFP
      localizes to the nucleus throughout the cell cycle. dcn1-deletion (dcn1Delta)
      leads to chromosome and kinetochore lagging at anaphase, resulting from delayed
      and attenuated cohesin cleavage and sister chromatids separation. These results
      put Dcn1 upstream of the anaphase promoting complex/cyclosome (APC/C) pathway. We
      propose a mechanism for Dcn1 function at mitosis.

PMID- 28455356
TI  - The coordinating role of IQGAP1 in the regulation of local, endosome-specific
      actin networks.
AB  - IQGAP1 is a large, multi-domain scaffold that helps orchestrate cell signaling
      and cytoskeletal mechanics by controlling interactions among a spectrum of
      receptors, signaling intermediates, and cytoskeletal proteins. While this
      coordination is known to impact cell morphology, motility, cell adhesion, and
      vesicular traffic, among other functions, the spatiotemporal properties and
      regulatory mechanisms of IQGAP1 have not been fully resolved. Herein, we describe
      a series of super-resolution and live-cell imaging analyses that identified a
      role for IQGAP1 in the regulation of an actin cytoskeletal shell surrounding a
      novel membranous compartment that localizes selectively to the basal cortex of
      polarized epithelial cells (MCF-10A). We also show that IQGAP1 appears to both
      stabilize the actin coating and constrain its growth. Loss of compartmental
      IQGAP1 initiates a disassembly mechanism involving rapid and unconstrained actin
      polymerization around the compartment and dispersal of its vesicle contents.
      Together, these findings suggest IQGAP1 achieves this control by harnessing both
      stabilizing and antagonistic interactions with actin. They also demonstrate the
      utility of these compartments for image-based investigations of the spatial and
      temporal dynamics of IQGAP1 within endosome-specific actin networks.

PMID- 28455360
TI  - Rb Loss and KRAS Mutation Are Predictors of the Response to Platinum-Based
      Chemotherapy in Pancreatic Neuroendocrine Neoplasm with Grade 3: A Japanese
      Multicenter Pancreatic NEN-G3 Study.
AB  - Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3)
      show variable responses to platinum-based chemotherapy. Recent studies indicated
      that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET
      G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3
      and assessed the responsiveness to chemotherapy and survival.Experimental Design:
      A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and
      after central review characteristics of each histologic subtype [NET-G3 vs.
      pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical,
      radiological, and molecular features. Factors that correlate with response to
      chemotherapy and survival were assessed.Results: Seventy patients analyzed
      included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling
      index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS
      (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and
      KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based
      chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3.
      Chemotherapeutic outcomes were worse in NET-G3 (P < 0.001). When we stratified
      PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS
      showed significantly higher RRs to platinum-based chemotherapy than those without
      (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS, 77% versus wild type,
      23%, P = 0.023). Rb was a predictive marker of response to platinum-based
      chemotherapy even in NEC-G3 (P = 0.035).Conclusions: NET-G3 and NEC-G3 showed
      distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to
      platinum-based chemotherapy. Rb and KRAS are promising predictors of response to
      platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res;
      23(16); 4625-32. (c)2017 AACR.

PMID- 28455361
TI  - What is the difference in concussion management in children as compared with
      adults? A systematic review.
AB  - AIM: To evaluate the evidence regarding the management of sport-related
      concussion (SRC) in children and adolescents. The eight subquestions included the
      effects of age on symptoms and outcome, normal and prolonged duration, the role
      of computerised neuropsychological tests (CNTs), the role of rest, and strategies
      for return to school and return to sport (RTSp). DESIGN: Systematic review. DATA
      SOURCES: MEDLINE (OVID), Embase (OVID) and PsycInfo (OVID). ELIGIBILITY CRITERIA
      FOR SELECTING STUDIES: Studies were included if they were original research on
      SRC in children aged 5 years to 18 years, and excluded if they were review
      articles, or did not focus on childhood SRC. RESULTS: A total of 5853 articles
      were identified, and 134 articles met the inclusion criteria. Some articles were
      common to multiple subquestions. Very few studies examined SRC in young children,
      aged 5-12 years. SUMMARY/CONCLUSIONS: This systematic review recommends that in
      children: child and adolescent age-specific paradigms should be applied; child
      validated symptom rating scales should be used; the widespread routine use of
      baseline CNT is not recommended; the expected duration of symptoms associated
      with SRC is less than 4 weeks; prolonged recovery be defined as symptomatic for
      greater than 4 weeks; a brief period of cognitive and physical rest should be
      followed with gradual symptom-limited physical and cognitive activity; all
      schools be encouraged to have a concussion policy and should offer appropriate
      academic accommodations and support to students recovering from SRC; and children
      and adolescents should not RTSp until they have successfully returned to school,
      however early introduction of symptom-limited physical activity is appropriate.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2016:CRD42016039184.

PMID- 28455362
TI  - A systematic review of potential long-term effects of sport-related concussion.
AB  - OBJECTIVE: Systematic review of possible long-term effects of sports-related
      concussion in retired athletes. DATA SOURCES: Ten electronic databases. STUDY
      SELECTION: Original research; incidence, risk factors or causation related to
      long-term mental health or neurological problems; individuals who have suffered a
      concussion; retired athletes as the subjects and possible long-term sequelae
      defined as >10 years after the injury. DATA EXTRACTION: Study population,
      exposure/outcome measures, clinical data, neurological examination findings,
      cognitive assessment, neuroimaging findings and neuropathology results. Risk of
      bias and level of evidence were evaluated by two authors. RESULTS: Following
      review of 3819 studies, 47 met inclusion criteria. Some former athletes have
      depression and cognitive deficits later in life, and there is an association
      between these deficits and multiple prior concussions. Former athletes are not at
      increased risk for death by suicide (two studies). Former high school American
      football players do not appear to be at increased risk for later life
      neurodegenerative diseases (two studies). Some retired professional American
      football players may be at increased risk for diminishment in cognitive
      functioning or mild cognitive impairment (several studies), and neurodegenerative
      diseases (one study). Neuroimaging studies show modest evidence of
      macrostructural, microstructural, functional and neurochemical changes in some
      athletes. CONCLUSION: Multiple concussions appear to be a risk factor for
      cognitive impairment and mental health problems in some individuals. More
      research is needed to better understand the prevalence of chronic traumatic
      encephalopathy and other neurological conditions and diseases, and the extent to
      which they are related to concussions and/or repetitive neurotrauma sustained in
      sports.

PMID- 28455363
TI  - What is the physiological time to recovery after concussion? A systematic review.
AB  - AIM OR OBJECTIVE: The aim of this study is to consolidate studies of
      physiological measures following sport-related concussion (SRC) to determine if a
      time course of postinjury altered neurobiology can be outlined. This biological
      time course was considered with respect to clinically relevant outcomes such as
      vulnerability to repeat injury and safe timing of return to physical contact
      risk. DESIGN: Systematic review. DATA SOURCES: PubMed, CINAHL, Cochrane Central,
      PsychINFO. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if
      they reported original research on physiological or neurobiological changes after
      SRC. Excluded were cases series <5 subjects, reviews, meta-analyses, editorials,
      animal research and research not pertaining to SRC. RESULTS: A total of 5834
      articles were identified, of which 80 were included for full-text data extraction
      and review. Relatively few longitudinal studies exist that follow both
      physiological dysfunction and clinical measures to recovery. SUMMARY/CONCLUSIONS:
      Modalities of measuring physiological change after SRC were categorised into the
      following: functional MRI, diffusion tensor imaging, magnetic resonance
      spectroscopy, cerebral blood flow, electrophysiology, heart rate, exercise, fluid
      biomarkers and transcranial magnetic stimulation. Due to differences in
      modalities, time course, study design and outcomes, it is not possible to define
      a single 'physiological time window' for SRC recovery. Multiple studies suggest
      physiological dysfunction may outlast current clinical measures of recovery,
      supporting a buffer zone of gradually increasing activity before full contact
      risk. Future studies need to use generalisable populations, longitudinal designs
      following to physiological and clinical recovery and careful correlation of
      neurobiological modalities with clinical measures.

PMID- 28455365
TI  - A unique opportunity to use football to improve birth registration awareness and
      completeness in Nigeria.

PMID- 28455364
TI  - Role of advanced neuroimaging, fluid biomarkers and genetic testing in the
      assessment of sport-related concussion: a systematic review.
AB  - OBJECTIVE: To conduct a systematic review of published literature on advanced
      neuroimaging, fluid biomarkers and genetic testing in the assessment of sport
      related concussion (SRC). DATA SOURCES: Computerised searches of Medline, PubMed,
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO,
      Scopus and Cochrane Library from 1 January 2000 to 31 December 2016 were done.
      There were 3222 articles identified. STUDY SELECTION: In addition to medical
      subject heading terms, a study was included if (1) published in English, (2)
      represented original research, (3) involved human research, (4) pertained to SRC
      and (5) involved data from neuroimaging, fluid biomarkers or genetic testing
      collected within 6 months of injury. Ninety-eight studies qualified for review
      (76 neuroimaging, 16 biomarkers and 6 genetic testing). DATA EXTRACTION: Separate
      reviews were conducted for neuroimaging, biomarkers and genetic testing. A
      standardised data extraction tool was used to document study design, population,
      tests employed and key findings. Reviewers used a modified quality assessment of
      studies of diagnostic accuracy studies (QUADAS-2) tool to rate the risk of bias,
      and a modified Grading of Recommendations Assessment, Development, and Evaluation
      (GRADE) system to rate the overall level of evidence for each search. DATA
      SYNTHESIS: Results from the three respective reviews are compiled in separate
      tables and an interpretive summary of the findings is provided. CONCLUSIONS:
      Advanced neuroimaging, fluid biomarkers and genetic testing are important
      research tools, but require further validation to determine their ultimate
      clinical utility in the evaluation of SRC. Future research efforts should address
      current gaps that limit clinical translation. Ultimately, research on
      neurobiological and genetic aspects of SRC is predicted to have major
      translational significance to evidence-based approaches to clinical management of
      SRC, much like applied clinical research has had over the past 20 years.

PMID- 28455366
TI  - Effect of cardiorespiratory and strength exercises on disease activity in
      patients with inflammatory rheumatic diseases: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To investigate the effects of cardiorespiratory and strength exercises
      on disease activity for patients with inflammatory rheumatic diseases (IRDs).
      DESIGN: A systematic review with meta-analysis registered at PROSPERO
      (CRD42015020004). PARTICIPANTS: Patients with IRDs. DATA SOURCES: The databases
      MEDLINE, AMED, Embase and CINAHL were searched from inception up to April 2016.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Trials were included if they were
      randomised controlled trials of adults with IRDs, comparing the effect of
      cardiorespiratory and strength exercises with usual care on disease activity and
      followed the American College of Sports Medicine's exercise recommendations. The
      primary outcome was disease activity in terms of inflammation, joint damage and
      symptoms. DATA SYNTHESIS: Data were pooled in a random-effect model for all
      outcomes, and standardised mean differences (SMDs) were calculated. The quality
      of evidence was evaluated according to the Grading of Recommendations Assessment,
      Development and Evaluation approach. RESULTS: Twenty-six trials with a total of
      1286 participants were included. There was high to moderate quality evidence, for
      a small beneficial effect on disease activity scores (0.19 (95% CI 0.05 to 0.33),
      p<0.01) and joint damage (SMD 0.27 (95% CI 0.07 to 0.46), p<0.01). Furthermore,
      moderate quality evidence for a small beneficial effect on erythrocyte
      sedimentation rate (SMD 0.20 (95% CI 0.0 to 0.39), p=0.04) and for no effect on C
      reactive protein (SMD -0.14 (95% CI -0.37 to 0.08), p=0.21). Beneficial effects
      were also seen for symptoms. CONCLUSIONS: The results of this review suggest
      beneficial effects of exercises on inflammation, joint damage and symptoms in
      patients with IRDs.

PMID- 28455368
TI  - Is it time to loosen the restrictions on athletes with cardiac disorders
      competing in sport?

PMID- 28455369
TI  - Complement C5aR1 Signaling Promotes Polarization and Proliferation of Embryonic
      Neural Progenitor Cells through PKCzeta.
AB  - The complement system, typically associated with innate immunity, is emerging as
      a key controller of nonimmune systems including in development, with recent
      studies linking complement mutations with neurodevelopmental disease. A key
      effector of the complement response is the activation fragment C5a, which,
      through its receptor C5aR1, is a potent driver of inflammation. Surprisingly,
      C5aR1 is also expressed during early mammalian embryogenesis; however, no clearly
      defined function is ascribed to C5aR1 in development. Here we demonstrate
      polarized expression of C5aR1 on the apical surface of mouse embryonic neural
      progenitor cells in vivo and on human embryonic stem cell-derived neural
      progenitors. We also show that signaling of endogenous C5a during mouse
      embryogenesis drives proliferation of neural progenitor cells within the
      ventricular zone and is required for normal brain histogenesis. C5aR1 signaling
      in neural progenitors was dependent on atypical protein kinase C zeta, a mediator
      of stem cell polarity, with C5aR1 inhibition reducing proliferation and symmetric
      division of apical neural progenitors in human and mouse models. C5aR1 signaling
      was shown to promote the maintenance of cell polarity, with exogenous C5a
      increasing the retention of polarized rosette architecture in human neural
      progenitors after physical or chemical disruption. Transient inhibition of C5aR1
      during neurogenesis in developing mice led to behavioral abnormalities in both
      sexes and MRI-detected brain microstructural alterations, in studied males,
      demonstrating a requirement of C5aR1 signaling for appropriate brain development.
      This study thus identifies a functional role for C5a-C5aR1 signaling in mammalian
      neurogenesis and provides mechanistic insight into recently identified complement
      gene mutations and brain disorders.SIGNIFICANCE STATEMENT The complement system,
      traditionally known as a controller of innate immunity, now stands as a
      multifaceted signaling family with a broad range of physiological actions. These
      include roles in the brain, where complement activation is associated with
      diseases, including epilepsy and schizophrenia. This study has explored
      complement regulation of neurogenesis, identifying a novel relationship between
      the complement activation peptide C5a and the neural progenitor proliferation
      underpinning formation of the mammalian brain. C5a was identified as a regulator
      of cell polarity, with inhibition of C5a receptors during embryogenesis leading
      to abnormal brain development and behavioral deficits. This work demonstrates
      mechanisms through which dysregulation of complement causes developmental disease
      and highlights the potential risk of complement inhibition for therapeutic
      purposes in pregnancy.

PMID- 28455371
TI  - Mandatory reporting of medically unsafe drivers is common sense.

PMID- 28455370
TI  - Decorrelated Input Dissociates Narrow Band gamma Power and BOLD in Human Visual
      Cortex.
AB  - Although fMRI using the BOLD contrast is widely used for noninvasively mapping
      hemodynamic brain activity in humans, its exact link to underlying neural
      processing is poorly understood. Whereas some studies have reported that BOLD
      signals measured in visual cortex are tightly linked to neural activity in the
      narrow band gamma (NBG) range, others have found a weak correlation between the
      two. To elucidate the mechanisms behind these conflicting findings, we
      hypothesized that BOLD reflects the strength of synaptic inputs to cortex,
      whereas NBG is more dependent on how well these inputs are correlated. To test
      this, we measured NBG, BOLD, and cerebral blood flow responses to stimuli that
      either correlate or decorrelate neural activity in human visual cortex. Next, we
      simulated a recurrent network model of excitatory and inhibitory neurons that
      reproduced in detail the experimental NBG and BOLD data. Results show that the
      visually evoked BOLD response was solely predicted by the sum of local inputs,
      whereas NBG was critically dependent on how well these inputs were correlated. In
      summary, the NBG-BOLD relationship strongly depends on the nature of sensory
      input to cortex: stimuli that increase the number of correlated inputs to visual
      cortex will increase NBG and BOLD in a similar manner, whereas stimuli that
      increase the number of decorrelated inputs will dissociate the two. The NBG-BOLD
      relationship is therefore not fixed but is rather highly dependent on input
      correlations that are both stimulus- and state-dependent.SIGNIFICANCE STATEMENT
      It is widely believed that gamma oscillations in cortex are tightly linked to
      local hemodynamic activity. Here, we present experimental evidence showing how a
      stimulus can increase local blood flow to the brain despite suppressing gamma
      power. Moreover, using a sophisticated model of cortical neurons, it is proposed
      that this occurs when synaptic input to cortex is strong yet decorrelated.
      Because input correlations are largely determined by the state of the brain, our
      results demonstrate that the relationship between gamma and local hemodynamics is
      not fixed, but rather context dependent. This likely explains why certain
      neurodevelopmental disorders are characterized by weak gamma activity despite
      showing normal blood flow.

PMID- 28455372
TI  - Regulation of neuromuscular junction organization by Rab2 and its effector ICA69
      in Drosophila.
AB  - The mechanisms underlying synaptic differentiation, which involves neuronal
      membrane and cytoskeletal remodeling, are not completely understood. We performed
      a targeted RNAi-mediated screen of Drosophila BAR-domain proteins and identified
      islet cell autoantigen 69 kDa (ICA69) as one of the key regulators of
      morphological differentiation of the larval neuromuscular junction (NMJ). We show
      that Drosophila ICA69 colocalizes with alpha-Spectrin at the NMJ. The conserved N
      BAR domain of ICA69 deforms liposomes in vitro Full-length ICA69 and the ICAC but
      not the N-BAR domain of ICA69 induce filopodia in cultured cells. Consistent with
      its cytoskeleton regulatory role, ICA69 mutants show reduced alpha-Spectrin
      immunoreactivity at the larval NMJ. Manipulating levels of ICA69 or its
      interactor PICK1 alters the synaptic level of ionotropic glutamate receptors
      (iGluRs). Moreover, reducing PICK1 or Rab2 levels phenocopies ICA69 mutation.
      Interestingly, Rab2 regulates not only synaptic iGluR but also ICA69 levels.
      Thus, our data suggest that: (1) ICA69 regulates NMJ organization through a
      pathway that involves PICK1 and Rab2, and (2) Rab2 functions genetically upstream
      of ICA69 and regulates NMJ organization and targeting/retention of iGluRs by
      regulating ICA69 levels.

PMID- 28455374
TI  - New alleles of the wheat domestication gene Q reveal multiple roles in growth and
      reproductive development.
AB  - The advantages of free threshing in wheat led to the selection of the
      domesticated Q allele, which is now present in almost all modern wheat varieties.
      Q and the pre-domestication allele, q, encode an AP2 transcription factor, with
      the domesticated allele conferring a free-threshing character and a subcompact
      (i.e. partially compact) inflorescence (spike). We demonstrate that mutations in
      the miR172 binding site of the Q gene are sufficient to increase transcript
      levels via a reduction in miRNA-dependent degradation, consistent with the
      conclusion that a single nucleotide polymorphism in the miRNA binding site of Q
      relative to q was essential in defining the modern Q allele. We describe novel
      gain- and loss-of-function alleles of Q and use these to define new roles for
      this gene in spike development. Q is required for the suppression of 'sham
      ramification', and increased Q expression can lead to the formation of ectopic
      florets and spikelets (specialized inflorescence branches that bear florets and
      grains), resulting in a deviation from the canonical spike and spikelet
      structures of domesticated wheat.

PMID- 28455373
TI  - ChIP-seq analysis of genomic binding regions of five major transcription factors
      highlights a central role for ZIC2 in the mouse epiblast stem cell gene
      regulatory network.
AB  - To obtain insight into the transcription factor (TF)-dependent regulation of
      epiblast stem cells (EpiSCs), we performed ChIP-seq analysis of the genomic
      binding regions of five major TFs. Analysis of in vivo biotinylated ZIC2, OTX2,
      SOX2, POU5F1 and POU3F1 binding in EpiSCs identified several new features. (1)
      Megabase-scale genomic domains rich in ZIC2 peaks and genes alternate with those
      rich in POU3F1 but sparse in genes, reflecting the clustering of regulatory
      regions that act at short and long-range, which involve binding of ZIC2 and
      POU3F1, respectively. (2) The enhancers bound by ZIC2 and OTX2 prominently
      regulate TF genes in EpiSCs. (3) The binding sites for SOX2 and POU5F1 in mouse
      embryonic stem cells (ESCs) and EpiSCs are divergent, reflecting the shift in the
      major acting TFs from SOX2/POU5F1 in ESCs to OTX2/ZIC2 in EpiSCs. (4) This shift
      in the major acting TFs appears to be primed by binding of ZIC2 in ESCs at
      relevant genomic positions that later function as enhancers following the
      disengagement of SOX2/POU5F1 from major regulatory functions and subsequent
      binding by OTX2. These new insights into EpiSC gene regulatory networks gained
      from this study are highly relevant to early stage embryogenesis.

PMID- 28455375
TI  - microRNA172 plays a crucial role in wheat spike morphogenesis and grain
      threshability.
AB  - Wheat domestication from wild species involved mutations in the Q gene. The q
      allele (wild wheats) is associated with elongated spikes and hulled grains,
      whereas the mutant Q allele (domesticated wheats) confers subcompact spikes and
      free-threshing grains. Previous studies showed that Q encodes an AP2-like
      transcription factor, but the causal polymorphism of the domestication traits
      remained unclear. Here, we show that the interaction between microRNA172 (miR172)
      and the Q allele is reduced by a single nucleotide polymorphism in the miRNA
      binding site. Inhibition of miR172 activity by a miRNA target mimic resulted in
      compact spikes and transition from glumes to florets in apical spikelets. By
      contrast, overexpression of miR172 was sufficient to induce elongated spikes and
      non-free-threshing grains, similar to those observed in three Q loss-of-function
      mutations. These lines showed transitions from florets to glumes in the basal
      spikelets. These localized homeotic changes were associated with opposing
      miR172/Q gradients along the spike. We propose that the selection of a nucleotide
      change at the miR172 binding site of Q contributed to subcompact spikes and free
      threshing grains during wheat domestication.

PMID- 28455377
TI  - Lmx1b-targeted cis-regulatory modules involved in limb dorsalization.
AB  - Lmx1b is a homeodomain transcription factor responsible for limb dorsalization.
      Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of
      function) limb phenotypes, no direct gene targets in the limb have been
      confirmed. To determine direct targets, we performed a chromatin
      immunoprecipitation against Lmx1b in mouse limbs at embryonic day 12.5 followed
      by next-generation sequencing (ChIP-seq). Nearly 84% (n=617) of the Lmx1b-bound
      genomic intervals (LBIs) identified overlap with chromatin regulatory marks
      indicative of potential cis-regulatory modules (PCRMs). In addition, 73 LBIs
      mapped to CRMs that are known to be active during limb development. We compared
      Lmx1b-bound PCRMs with genes regulated by Lmx1b and found 292 PCRMs within 1 Mb
      of 254 Lmx1b-regulated genes. Gene ontological analysis suggests that Lmx1b
      targets extracellular matrix production, bone/joint formation, axonal guidance,
      vascular development, cell proliferation and cell movement. We validated the
      functional activity of a PCRM associated with joint-related Gdf5 that provides a
      mechanism for Lmx1b-mediated joint modification and a PCRM associated with Lmx1b
      that suggests a role in autoregulation. This is the first report to describe
      genome-wide Lmx1b binding during limb development, directly linking Lmx1b to
      targets that accomplish limb dorsalization.

PMID- 28455379
TI  - Robert Desmond Gibson Creery.

PMID- 28455378
TI  - G9a controls placental vascular maturation by activating the Notch Pathway.
AB  - Defective fetoplacental vascular maturation causes intrauterine growth
      restriction (IUGR). A transcriptional switch initiates placental maturation,
      during which blood vessels elongate. However, the cellular mechanisms and
      regulatory pathways involved are unknown. We show that the histone
      methyltransferase G9a, also known as Ehmt2, activates the Notch pathway to
      promote placental vascular maturation. Placental vasculature from embryos with
      G9a-deficient endothelial progenitor cells failed to expand owing to decreased
      endothelial cell proliferation and increased trophoblast proliferation. Moreover,
      G9a deficiency altered the transcriptional switch initiating placental maturation
      and caused downregulation of Notch pathway effectors including Rbpj Importantly,
      Notch pathway activation in G9a-deficient endothelial progenitors extended
      embryonic life and rescued placental vascular expansion. Thus, G9a activates the
      Notch pathway to balance endothelial cell and trophoblast proliferation and
      coordinates the transcriptional switch controlling placental vascular maturation.
      Accordingly, G9A and RBPJ were downregulated in human placentae from IUGR
      affected pregnancies, suggesting that G9a is an important regulator in placental
      diseases caused by defective vascular maturation.

PMID- 28455376
TI  - Negative regulation of endothelin signaling by SIX1 is required for proper
      maxillary development.
AB  - Jaw morphogenesis is a complex event mediated by inductive signals that establish
      and maintain the distinct developmental domains required for formation of hinged
      jaws, the defining feature of gnathostomes. The mandibular portion of pharyngeal
      arch 1 is patterned dorsally by Jagged-Notch signaling and ventrally by
      endothelin receptor A (EDNRA) signaling. Loss of EDNRA signaling disrupts normal
      ventral gene expression, the result of which is homeotic transformation of the
      mandible into a maxilla-like structure. However, loss of Jagged-Notch signaling
      does not result in significant changes in maxillary development. Here we show in
      mouse that the transcription factor SIX1 regulates dorsal arch development not
      only by inducing dorsal Jag1 expression but also by inhibiting endothelin 1
      (Edn1) expression in the pharyngeal endoderm of the dorsal arch, thus preventing
      dorsal EDNRA signaling. In the absence of SIX1, but not JAG1, aberrant EDNRA
      signaling in the dorsal domain results in partial duplication of the mandible.
      Together, our results illustrate that SIX1 is the central mediator of dorsal
      mandibular arch identity, thus ensuring separation of bone development between
      the upper and lower jaws.

PMID- 28455380
TI  - US targets companies touting unproven cancer cures.

PMID- 28455381
TI  - Eric Lewis Blair.

PMID- 28455382
TI  - Endovascular therapy for ischemic stroke: Save a minute-save a week.
AB  - OBJECTIVE: To quantify the patient lifetime benefits gained from reduced delays
      in endovascular therapy for acute ischemic stroke. METHODS: We used observational
      prospective data of consecutive stroke patients treated with IV thrombolysis in
      Helsinki (1998-2014; n = 2,474) to describe distributions of age, sex, stroke
      severity, onset-to-treatment times, and 3-month modified Rankin Scale (mRS) in
      routine clinical practice. We used treatment effects by time of endovascular
      therapy in large vessel occlusion over and above thrombolysis as reported by the
      Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute
      Ischemic Stroke in the Netherlands (MR CLEAN) study to model the shift in 3-month
      mRS distributions with reducing treatment delays. From the 3-month outcomes we
      derived patient-expected lifetimes and cumulative long-term disability with
      incremental treatment delay reductions. RESULTS: Each minute saved in onset-to
      treatment time granted on average 4.2 days of extra healthy life, with a 95%
      prediction interval 2.3-5.4. Women gained slightly more than men due to their
      longer life expectancies. Patients younger than 55 years with severe strokes of
      NIH Stroke Scale score above 10 gained more than a week per each minute saved. In
      the whole cohort, every 20 minutes decrease in treatment delays led to a gain of
      average equivalent of 3 months of disability-free life. CONCLUSIONS: Small
      reductions in endovascular delays lead to marked health benefits over patients'
      lifetimes. Services need to be optimized to reduce delays to endovascular
      therapy.

PMID- 28455383
TI  - Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta
      analysis.
AB  - OBJECTIVE: To summarize the evidence on immunoablative therapy followed by
      autologous hematopoietic stem cell transplantation (aHSCT) to manage severe and
      treatment-refractory multiple sclerosis (MS). METHODS: We collected all the
      published studies of aHSCT in any form of MS from 1995 to 2016, carefully
      excluding reports that were updated in subsequent studies. Endpoints were
      transplant-related mortality (TRM), rate of disease progression, and no evidence
      of disease activity (NEDA) status. A weighted metaregression based on a Poisson
      model was run, assessing whether there were study-specific characteristics with
      an effect on TRM and progression. RESULTS: Fifteen studies including 764
      transplanted patients were pooled in the meta-analysis. The pooled estimate of
      TRM was 2.1% (95% confidence interval [CI] 1.3%-3.4%). TRM was higher in older
      studies (p = 0.014) and in studies with a lower proportion of patients with
      relapsing-remitting MS (RRMS) (p = 0.028). A higher baseline Expanded Disability
      Status Scale (p = 0.013) was also significantly associated with a higher TRM.
      Pooled rate of progression was 17.1% at 2 years (95% CI 9.7%-24.5%) and 23.3%
      (95% CI 16.3%-31.8%) at 5 years. Lower 2-year progression rate was significantly
      associated with higher proportions of patients with RRMS (p = 0.004). The pooled
      proportion of NEDA patients at 2 years was 83% (range 70%-92%) and at 5 years was
      67% (range 59%-70%). CONCLUSIONS: The emerging evidence on this therapeutic
      approach in MS indicates that the largest benefit/risk profile form this
      therapeutic approach can be obtained in patients with aggressive MS with a
      relapsing-remitting course and who have not yet accumulated a high level of
      disability.

PMID- 28455384
TI  - Autologous hematopoietic stem cell transplantation for MS: Safer than previously
      thought.

PMID- 28455385
TI  - Endovascular thrombectomy: Time is still brain.

PMID- 28455386
TI  - Monthly variation in pediatric visits for headache to US emergency departments.
AB  - Headache is a common pediatric symptom often associated with stress and fatigue
      which may be more common during the school year. The purpose of this study is to
      determine if visits for headache are more common during the months of the school
      year. This study is a secondary analysis of the National Hospital Ambulatory
      Medical Care Survey (NHAMCS) database from 2001 to 2010. Patient visits in those
      aged 18 years or younger not associated with injury were examined. Only visits
      with an International Classification of Diseases, ninth revision (ICD-9) code
      consistent with headache were included. Data were analyzed using cumulative
      binomial probabilities. This statistic was used to establish the chance of seeing
      up to the observed number of visits for headache in a given month assuming that
      all months have an equal number of visits. A total of 660 unweighted visits
      representing 3.2 million patient encounters met the inclusion and exclusion
      criteria. Visits for headache were more common during the months of January,
      September, and October and less common in March, April, July, and November.
      Subgroup analysis was performed for children aged 13-18 years. In this subgroup,
      headaches were more common in January, September, and October. They were less
      common in July and December. Headache is more common during the first 2 months
      back to school in the fall as well as after the winter break in January. While we
      are not able to establish causality, we propose that children with headache
      require additional attention during the school year, particularly in the months
      following summer and winter breaks.

PMID- 28455387
TI  - Will the real bile acid sulfotransferase please stand up? Identification of
      Sult2a8 as a major hepatic bile acid sulfonating enzyme in mice.

PMID- 28455388
TI  - PCDH19-related epilepsy: a rare but recognisable clinical syndrome in females.
AB  - Protocadherin 19 (PCDH19)-related epilepsy (OMIM 300088) is a distinctive
      clinical syndrome limited to females. We describe a 17-year-old girl who
      presented to a regional epilepsy clinic with a history of recurrent febrile
      seizures in infancy. Genetic analysis of the PCDH19 gene revealed a novel
      heterozygous mutation within a highly conserved region of the gene. Patients with
      PCDH19 mutations present with clusters of seizures associated with fever. While
      fever-induced seizures are common to children with PCDH19 and SCN1A mutations,
      there are certain clinical features that distinguish these genetic syndromes from
      each other. PCDH19 mutation demonstrates an unusual form of transmission such
      that only heterozygous females develop the phenotype. De novo mutations account
      for most cases although the inheritance is sometimes familial patterns of
      inheritance. Hemizygous males are typically unaffected. Identification of the
      mutation provides patients and their families with an explanation for their
      clinical presentation, important prognostic information and an opportunity for
      genetic counselling.

PMID- 28455389
TI  - The neurology of ageing: what is normal?
AB  - Ageing is associated with changes in the nervous system with consequent
      alterations in some neurological examination findings: understanding what is
      'normal' at different ages is essential when evaluating patients. In seminal
      papers published in 1931, Dr MacDonald Critchley summarised his observations and
      the prevailing evidence on the effects of ageing on, among others, sensation,
      reflexes, ocular function, olfaction, movement and cognition. In this review,
      these observations are re-evaluated in light of contemporary evidence. Factors
      influencing the measurement and interpretation of these clinical findings are
      then discussed, including reproducibility, the influence of comorbidities,
      secular trends, how 'normality' should best be defined, the problems of
      extrapolating group data to individuals and the influence of presymptomatic
      neurodegenerative disease states. The case is made that context is critical, and
      that combining life course data with detailed clinical and biomarker phenotyping
      is required to understand the determinants of normal neurological function
      associated with ageing.

PMID- 28455390
TI  - Global functions of extracellular, transmembrane and cytoplasmic domains of
      organic solute transporter beta-subunit.
AB  - Transport of bile acids across the basolateral membrane of the intestinal
      enterocyte is carried out by the organic solute transporter (Ost) composed of a
      seven-transmembrane domain (TMD) subunit (Ostalpha) and an ancillary single TMD
      subunit (Ostbeta). Although previous investigations have demonstrated the
      importance of the TMD of Ostbeta for its activity, further studies were conducted
      to assess the contributions of other regions of the Ostbeta subunit. Transport
      activity was retained when Ostbeta was truncated to contain only the TMD with 15
      additional residues on each side and co-expressed with Ostalpha, whereas shorter
      fragments were inactive. To probe the broader functions of Ostbeta segments,
      chimeric proteins were constructed in which N-terminal, TMD or C-terminal regions
      of Ostbeta were fused to corresponding regions of receptor activity-modifying
      protein (RAMP1), a single TMD protein required by several seven-TMD G-protein
      coupled receptors including the calcitonin receptor-like receptor (CLR).
      Ostbeta/RAMP1 chimeras were expressed with Ostalpha and CLR. As expected,
      replacing the Ostbeta TMD abolished transport activity; however, replacing either
      the entire N-terminal or entire C-terminal domain of Ostbeta with RAMP1 sequences
      did not prevent plasma membrane localization or the ability to support
      [3H]taurocholate uptake. Co-immunoprecipitation experiments revealed that the C
      terminus of Ostbeta is a previously unrecognized site of interaction with
      Ostalpha. All chimeras containing N-terminal RAMP1 segments allowed co-expressed
      CLR to respond to agonists with strong increases in cyclic AMP. These results
      provide new insights into the structure and function of the heteromeric Ost
      transporter complex.

PMID- 28455391
TI  - NHS managers should face same regulation as doctors, says Francis.

PMID- 28455395
TI  - Three Cancer Researchers Win CZ Biohub Prizes.
AB  - Three cancer researchers are among the first of 47 investigators to receive 5
      years of funding through the Chan Zuckerberg Biohub. The financial awards,
      granted to scientists at the Biohub's three member institutions, will support
      early stage, high-risk foundational work at the intersection of biology and
      engineering.

PMID- 28455399
TI  - Drug Blocks Synaptic Hijacking in Gliomas.
AB  - An enzyme called ADAM10 cleaves a protein found in synaptic membranes, creating a
      soluble factor that can fuel the growth of brain tumors. Blocking this enzyme
      shrinks tumors in xenograft models of pediatric glioblastoma and diffuse
      intrinsic pontine glioma, two brain cancers with few to no effective drug
      options, researchers reported at the American Academy of Neurology 2017 Annual
      Meeting.

PMID- 28455400
TI  - Photosynthetic Efficiency as Bioindicator of Environmental Pressure in A.
      halleri.
AB  - In earlier ecophysiological studies that were conducted on Arabidopsis halleri
      plants, scientists focused on the mechanisms of Cd and Zn hyperaccumulation but
      did not take into consideration the environmental factors that can significantly
      affect the physiological responses of plants in situ. In this study, we
      investigated A. halleri that was growing on two nonmetalliferous and three
      metalliferous sites, which were characterized by different environmental
      conditions. We compared these populations in order to find differences within the
      metallicolous and nonmetallicolous groups that have not yet been investigated.
      The concentrations of several elements in the plant and soil samples also were
      investigated. To our knowledge, the concentration and fluorescence of chlorophyll
      were measured for A. halleri in situ for the first time. Our study confirmed the
      hyperaccumulation of Cd and Zn for each metallicolous population. For the
      metallicolous populations, the inhibition of parameters that describe the
      efficiency of the photosynthetic apparatus with increasing accumulations of heavy
      metals in the shoots also was observed. It was found that the nonmetallicolous
      plant populations from the summit of Ciemniak Mountain had larger antenna
      dimensions and chlorophyll content but a lower percentage of active reaction
      centers. To our knowledge, in this study, the internal high physiological
      diversity within the populations that inhabit metalliferous and nonmetalliferous
      sites is presented for the first time.

PMID- 28455392
TI  - Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF
      Melanoma.
AB  - Genomic diversity among melanoma tumors limits durable control with conventional
      and targeted therapies. Nevertheless, pathologic activation of the ERK1/2 pathway
      is a linchpin tumorigenic mechanism associated with the majority of primary and
      recurrent disease. Therefore, we sought to identify therapeutic targets that are
      selectively required for tumorigenicity in the presence of pathologic ERK1/2
      signaling. By integration of multigenome chemical and genetic screens, recurrent
      architectural variants in melanoma tumor genomes, and patient outcome data, we
      identified two mechanistic subtypes of BRAFV600 melanoma that inform new cancer
      cell biology and offer new therapeutic opportunities. Subtype membership defines
      sensitivity to clinical MEK inhibitors versus TBK1/IKBKepsilon inhibitors.
      Importantly, subtype membership can be predicted using a robust quantitative five
      feature genetic biomarker. This biomarker, and the mechanistic relationships
      linked to it, can identify a cohort of best responders to clinical MEK inhibitors
      and identify a cohort of TBK1/IKBKepsilon inhibitor-sensitive disease among
      nonresponders to current targeted therapy.Significance: This study identified two
      mechanistic subtypes of melanoma: (1) the best responders to clinical BRAF/MEK
      inhibitors (25%) and (2) nonresponders due to primary resistance mechanisms
      (9.9%). We identified robust biomarkers that can detect these subtypes in patient
      samples and predict clinical outcome. TBK1/IKBKepsilon inhibitors were
      selectively toxic to drug-resistant melanoma. Cancer Discov; 7(8); 832-51.
      (c)2017 AACR.See related commentary by Jenkins and Barbie, p. 799This article is
      highlighted in the In This Issue feature, p. 783.

PMID- 28455401
TI  - Roles of Dicer-Like Proteins 2 and 4 in Intra- and Intercellular Antiviral
      Silencing.
AB  - RNA silencing is an innate antiviral mechanism conserved in organisms across
      kingdoms. Such a cellular defense involves DICER or DICER-LIKEs (DCLs) that
      process plant virus RNAs into viral small interfering RNAs (vsiRNAs). Plants
      encode four DCLs that play diverse roles in cell-autonomous intracellular virus
      induced RNA silencing (known as VIGS) against viral invasion. VIGS can spread
      between cells. However, the genetic basis and involvement of vsiRNAs in non-cell
      autonomous intercellular VIGS remains poorly understood. Using GFP as a reporter
      gene together with a suite of DCL RNAi transgenic lines, here we show that
      despite the well-established activities of DCLs in intracellular VIGS and vsiRNA
      biogenesis, DCL4 acts to inhibit intercellular VIGS whereas DCL2 is required
      (likely along with DCL2-processed/dependent vsiRNAs and their precursor RNAs) for
      efficient intercellular VIGS trafficking from epidermal to adjacent cells. DCL4
      imposed an epistatic effect on DCL2 to impede cell-to-cell spread of VIGS. Our
      results reveal previously unknown functions for DCL2 and DCL4 that may form a
      dual defensive frontline for intra- and intercellular silencing to double-protect
      cells from virus infection in Nicotiana benthamiana.

PMID- 28455402
TI  - SDG2-Mediated H3K4me3 Is Crucial for Chromatin Condensation and Mitotic Division
      during Male Gametogenesis in Arabidopsis.
AB  - Epigenetic reprogramming occurring during reproduction is crucial for both animal
      and plant development. Histone H3 Lys 4 trimethylation (H3K4me3) is an
      evolutionarily conserved epigenetic mark of transcriptional active euchromatin.
      While much has been learned in somatic cells, H3K4me3 deposition and function in
      gametophyte is poorly studied. Here, we demonstrate that SET DOMAIN GROUP2 (SDG2)
      mediated H3K4me3 deposition participates in epigenetic reprogramming during
      Arabidopsis male gametogenesis. We show that loss of SDG2 barely affects meiosis
      and cell fate establishment of haploid cells. However, we found that SDG2 is
      critical for postmeiotic microspore development. Mitotic cell division
      progression is partly impaired in the loss-of-function sdg2-1 mutant,
      particularly at the second mitosis setting up the two sperm cells. We demonstrate
      that SDG2 is involved in promoting chromatin decondensation in the pollen
      vegetative nucleus, likely through its role in H3K4me3 deposition, which prevents
      ectopic heterochromatic H3K9me2 speckle formation. Moreover, we found that
      derepression of the LTR retrotransposon ATLANTYS1 is compromised in the
      vegetative cell of the sdg2-1 mutant pollen. Consistent with chromatin
      condensation and compromised transcription activity, pollen germination and
      pollen tube elongation, representing the key function of the vegetative cell in
      transporting sperm cells during fertilization, are inhibited in the sdg2-1
      mutant. Taken together, we conclude that SDG2-mediated H3K4me3 is an essential
      epigenetic mark of the gametophyte chromatin landscape, playing critical roles in
      gamete mitotic cell cycle progression and pollen vegetative cell function during
      male gametogenesis and beyond.

PMID- 28455403
TI  - Concerted Divergence after Gene Duplication in Polycomb Repressive Complexes.
AB  - Duplicated genes are a major contributor to genome evolution and phenotypic
      novelty. There are multiple possible evolutionary fates of duplicated genes.
      Here, we provide an example of concerted divergence of simultaneously duplicated
      genes whose products function in the same complex. We studied POLYCOMB REPRESSIVE
      COMPLEX2 (PRC2) in Brassicaceae. The VERNALIZATION (VRN)-PRC2 complex contains
      VRN2 and SWINGER (SWN), and both genes were duplicated during a whole-genome
      duplication to generate FERTILIZATION INDEPENDENT SEED2 (FIS2) and MEDEA (MEA),
      which function in the Brassicaceae-specific FIS-PRC2 complex that regulates seed
      development. We examined the expression of FIS2, MEA, and their paralogs,
      compared their cytosine and histone methylation patterns, and analyzed the
      sequence evolution of the genes. We found that FIS2 and MEA have reproductive
      specific expression patterns that are correlated and derived from the broadly
      expressed VRN2 and SWN in outgroup species. In vegetative tissues of Arabidopsis
      (Arabidopsis thaliana), repressive methylation marks are enriched in FIS2 and
      MEA, whereas active marks are associated with their paralogs. We detected
      comparable accelerated amino acid substitution rates in FIS2 and MEA but not in
      their paralogs. We also show divergence patterns of the PRC2-associated
      VERNALIZATION5/VIN3-LIKE2 that are similar to FIS2 and MEA These lines of
      evidence indicate that FIS2 and MEA have diverged in concert, resulting in
      functional divergence of the PRC2 complexes in Brassicaceae. This type of
      concerted divergence is a previously unreported fate of duplicated genes. In
      addition, the Brassicaceae-specific FIS-PRC2 complex modified the regulatory
      pathways in female gametophyte and seed development.

PMID- 28455405
TI  - Respiration driven excessive sinus tachycardia treated with clonidine.
AB  - A 26-year-old man presented to our syncope service with debilitating daily
      palpitations, shortness of breath, presyncope and syncope following a severe
      viral respiratory illness 4 years previously. Mobitz type II block had previously
      been identified, leading to a permanent pacemaker and no further episodes of
      frank syncope. Transthoracic echocardiography, electophysiological study and
      repeated urine metanepherines were normal. His palpitations and presyncope were
      reproducible on deep inspiration, coughing, isometric hand exercise and passive
      leg raises. We demonstrated rapid increases in heart rate with no change in
      morphology on his 12 lead ECG. His symptoms were resistant to fludrocortisone,
      flecainide, beta blockers and ivabradine. Initiation of clonidine in combination
      with ivabradine led to rapid resolution of his symptoms. We suggest that an
      excessive respiratory sinus arrhythmia was responsible for his symptoms and
      achieved an excellent response with the centrally acting sympatholytic clonidine,
      where previous peripherally acting treatments had failed.

PMID- 28455406
TI  - Role of narrow band imaging in the diagnostics of sinonasal pathology.
AB  - Malignancies of the nasal cavity and paranasal sinuses are well known, but have
      uncommon presentations. Late diagnosis and local extension are significant
      prognostic factors associated with a poorer treatment outcome. Thus, refinements
      of the diagnostic procedures to enhance the sensitivity of the clinical
      evaluation are desirable. We here describe a case of endonasal lymphoma, in which
      the lesion was hardly visible and initially ignored at ordinary white light (WLI)
      nasoendoscopy, but easily recognisable, clearly pathogenic and well demarcated
      when illuminated with narrow band imaging (NBI) at a later session. In general,
      with regard to mucosal-derived pathology of the upper aerodigestive tract, the
      diagnostic gain of NBI-assisted endoscopy in comparison with that of WLI has been
      proved in several articles. The focus has however been on neoplasm in
      laryngopharynx and oesophagus. The authors recommend broadening the use of NBI to
      include all evaluations of nasal mucosa, when malignancy is suspected.

PMID- 28455407
TI  - Masochistic enzymology: Dennis Vance's work on phosphatidylcholine.

PMID- 28455408
TI  - Occupancy of the zinc-binding site by transition metals decreases the substrate
      affinity of the human dopamine transporter by an allosteric mechanism.

PMID- 28455404
TI  - A Rice PECTATE LYASE-LIKE Gene Is Required for Plant Growth and Leaf Senescence.
AB  - To better understand the molecular mechanisms behind plant growth and leaf
      senescence in monocot plants, we identified a mutant exhibiting dwarfism and an
      early-senescence leaf phenotype, termed dwarf and early-senescence leaf1 (del1).
      Histological analysis showed that the abnormal growth was caused by a reduction
      in cell number. Further investigation revealed that the decline in cell number in
      del1 was affected by the cell cycle. Physiological analysis, transmission
      electron microscopy, and TUNEL assays showed that leaf senescence was triggered
      by the accumulation of reactive oxygen species. The DEL1 gene was cloned using a
      map-based approach. It was shown to encode a pectate lyase (PEL) precursor that
      contains a PelC domain. DEL1 contains all the conserved residues of PEL and has
      strong similarity with plant PelC. DEL1 is expressed in all tissues but
      predominantly in elongating tissues. Functional analysis revealed that mutation
      of DEL1 decreased the total PEL enzymatic activity, increased the degree of
      methylesterified homogalacturonan, and altered the cell wall composition and
      structure. In addition, transcriptome assay revealed that a set of cell wall
      function- and senescence-related gene expression was altered in del1 plants. Our
      research indicates that DEL1 is involved in both the maintenance of normal cell
      division and the induction of leaf senescence. These findings reveal a new
      molecular mechanism for plant growth and leaf senescence mediated by PECTATE
      LYASE-LIKE genes.

PMID- 28455409
TI  - DDR1 receptor tyrosine kinase promotes prosurvival pathway through Notch1
      activation.

PMID- 28455410
TI  - Into the linker's DENN: A tyrosine's control of autophagy.
AB  - The small GTP-binding protein Rab12 plays an important role in the initiation of
      starvation-induced macroautophagy (autophagy) and is activated by the guanine
      nucleotide exchange factor DENND3. However, the molecular mechanism by which
      DENND3 becomes activated has remained elusive. Xu and McPherson now identify a
      novel mechanism of DENND3 intramolecular binding that is regulated by the
      phosphorylation of a single tyrosine residue.

PMID- 28455411
TI  - The VPS34 PI3K negatively regulates RAB-5 during endosome maturation.
AB  - The GTPase Rab5 and phosphatidylinositol-3 phosphate [PI(3)P] coordinately
      regulate endosome trafficking. Rab5 recruits Vps34, the class III
      phosphoinositide 3-kinase (PI3K), to generate PI(3)P and recruit PI(3)P-binding
      proteins. Loss of Rab5 and loss of Vps34 have opposite effects on endosome size,
      suggesting that our understanding of how Rab5 and PI(3)P cooperate is incomplete.
      Here, we report a novel regulatory loop whereby Caenorhabditis elegans VPS-34
      inactivates RAB-5 via recruitment of the TBC-2 Rab GTPase-activating protein. We
      found that loss of VPS-34 caused a phenotype with large late endosomes, as with
      loss of TBC-2, and that Rab5 activity (mice have two Rab5 isoforms, Rab5a and
      Rab5b) is increased in Vps34-knockout mouse embryonic fibroblasts (Vps34 is also
      known as PIK3C3 in mammals). We found that VPS-34 is required for TBC-2 endosome
      localization and that the pleckstrin homology (PH) domain of TBC-2 bound PI(3)P.
      Deletion of the PH domain enhanced TBC-2 localization to endosomes in a VPS-34
      dependent manner. Thus, PI(3)P binding of the PH domain might be permissive for
      another PI(3)P-regulated interaction that recruits TBC-2 to endosomes. Therefore,
      VPS-34 recruits TBC-2 to endosomes to inactivate RAB-5 to ensure the
      directionality of endosome maturation.

PMID- 28455412
TI  - In vivo reprogramming of non-mammary cells to an epithelial cell fate is
      independent of amphiregulin signaling.
AB  - Amphiregulin (AREG)-/- mice demonstrate impaired mammary development and form
      only rudimentary ductal epithelial trees; however, AREG-/- glands are still
      capable of undergoing alveologenesis and lactogenesis during pregnancy.
      Transplantation of AREG-/- mammary epithelial cells into cleared mouse mammary
      fat pads results in a diminished capacity for epithelial growth (~15%) as
      compared to that of wild-type mammary epithelial cells. To determine whether
      estrogen receptor alpha (ERalpha, also known as ESR1) and/or AREG signaling were
      necessary for non-mammary cell redirection, we inoculated either ERalpha-/- or
      AREG-/- mammary cells with non-mammary progenitor cells (WAP-Cre/Rosa26LacZ+ male
      testicular cells or GFP-positive embryonic neuronal stem cells). ERalpha-/- cells
      possessed a limited ability to grow or reprogram non-mammary cells in
      transplanted mammary fat pads. AREG-/- mammary cells were capable of redirecting
      both types of non-mammary cell populations to mammary phenotypes in regenerating
      mammary outgrowths. Transplantation of fragments from AREG-reprogrammed chimeric
      outgrowths resulted in secondary outgrowths in six out of ten fat pads,
      demonstrating the self-renewing capacity of the redirected non-mammary cells to
      contribute new progeny to chimeric outgrowths. Nestin was detected at the leading
      edges of developing alveoli, suggesting that its expression may be essential for
      lobular expansion.

PMID- 28455413
TI  - Pseudostratified epithelia - cell biology, diversity and roles in organ formation
      at a glance.
AB  - Pseudostratified epithelia (PSE) are widespread and diverse tissue arrangements,
      and many PSE are organ precursors in a variety of organisms. While cells in PSE,
      like other epithelial cells, feature apico-basal polarity, they generally are
      more elongated and their nuclei are more densely packed within the tissue. In
      addition, nuclei in PSE undergo interkinetic nuclear migration (IKNM, also
      referred to as INM), whereby all mitotic events occur at the apical surface of
      the elongated epithelium. Previous reviews have focused on the links between IKNM
      and the cell cycle, as well as the relationship between IKNM and neurogenesis,
      which will not be elaborated on here. Instead, in this Cell Science at a Glance
      article and the accompanying poster, I will discuss the cell biology of PSEs,
      highlighting how differences in PSE architecture could influence cellular
      behaviour, especially IKNM. Furthermore, I will summarize what we know about the
      links between apical mitosis in PSE and tissue integrity and maturation.

PMID- 28455414
TI  - HDAC Inhibitors Disrupt Programmed Resistance to Apoptosis During Drosophila
      Development.
AB  - We have previously shown that the ability to respond to apoptotic triggers is
      regulated during Drosophila development, effectively dividing the fly life cycle
      into stages that are either sensitive or resistant to apoptosis. Here, we show
      that the developmentally programmed resistance to apoptosis involves
      transcriptional repression of critical proapoptotic genes by histone deacetylases
      (HDACs). Administration of HDAC inhibitors (HDACi), like trichostatin A or
      suberoylanilide hydroxamic acid, increases expression of proapoptotic genes and
      is sufficient to sensitize otherwise resistant stages. Conversely, reducing
      levels of proapoptotic genes confers resistance to otherwise sensitive stages.
      Given that resistance to apoptosis is a hallmark of cancer cells, and that HDACi
      have been recently added to the repertoire of FDA-approved agents for cancer
      therapy, our results provide new insights for how HDACi help kill malignant cells
      and also raise concerns for their potential unintended effects on healthy cells.

PMID- 28455415
TI  - Genomic-Enabled Prediction in Maize Using Kernel Models with Genotype *
      Environment Interaction.
AB  - Multi-environment trials are routinely conducted in plant breeding to select
      candidates for the next selection cycle. In this study, we compare the prediction
      accuracy of four developed genomic-enabled prediction models: (1) single
      environment, main genotypic effect model (SM); (2) multi-environment, main
      genotypic effects model (MM); (3) multi-environment, single variance G*E
      deviation model (MDs); and (4) multi-environment, environment-specific variance
      G*E deviation model (MDe). Each of these four models were fitted using two kernel
      methods: a linear kernel Genomic Best Linear Unbiased Predictor, GBLUP (GB), and
      a nonlinear kernel Gaussian kernel (GK). The eight model-method combinations were
      applied to two extensive Brazilian maize data sets (HEL and USP data sets),
      having different numbers of maize hybrids evaluated in different environments for
      grain yield (GY), plant height (PH), and ear height (EH). Results show that the
      MDe and the MDs models fitted with the Gaussian kernel (MDe-GK, and MDs-GK) had
      the highest prediction accuracy. For GY in the HEL data set, the increase in
      prediction accuracy of SM-GK over SM-GB ranged from 9 to 32%. For the MM, MDs,
      and MDe models, the increase in prediction accuracy of GK over GB ranged from 9
      to 49%. For GY in the USP data set, the increase in prediction accuracy of SM-GK
      over SM-GB ranged from 0 to 7%. For the MM, MDs, and MDe models, the increase in
      prediction accuracy of GK over GB ranged from 34 to 70%. For traits PH and EH,
      gains in prediction accuracy of models with GK compared to models with GB were
      smaller than those achieved in GY. Also, these gains in prediction accuracy
      decreased when a more difficult prediction problem was studied.

PMID- 28455418
TI  - Rita Phiroz Anklesaria.

PMID- 28455416
TI  - NuA4 Lysine Acetyltransferase Complex Contributes to Phospholipid Homeostasis in
      Saccharomyces cerevisiae.
AB  - Actively proliferating cells constantly monitor and readjust their metabolic
      pathways to ensure the replenishment of phospholipids necessary for membrane
      biogenesis and intracellular trafficking. In Saccharomyces cerevisiae, multiple
      studies have suggested that the lysine acetyltransferase complex NuA4 plays a
      role in phospholipid homeostasis. For one, NuA4 mutants induce the expression of
      the inositol-3-phosphate synthase gene, INO1, which leads to excessive
      accumulation of inositol, a key metabolite used for phospholipid biosynthesis.
      Additionally, NuA4 mutants also display negative genetic interactions with sec14
      1ts , a mutant of a lipid-binding gene responsible for phospholipid remodeling of
      the Golgi. Here, using a combination of genetics and transcriptional profiling,
      we explore the connections between NuA4, inositol, and Sec14 Surprisingly, we
      found that NuA4 mutants did not suppress but rather exacerbated the growth
      defects of sec14-1ts under inositol-depleted conditions. Transcriptome studies
      reveal that while loss of the NuA4 subunit EAF1 in sec14-1ts does derepress INO1
      expression, it does not derepress all inositol/choline-responsive phospholipid
      genes, suggesting that the impact of Eaf1 on phospholipid homeostasis extends
      beyond inositol biosynthesis. In fact, we find that NuA4 mutants have impaired
      lipid droplet levels and through genetic and chemical approaches, we determine
      that the genetic interaction between sec14-1ts and NuA4 mutants potentially
      reflects a role for NuA4 in fatty acid biosynthesis. Altogether, our work
      identifies a new role for NuA4 in phospholipid homeostasis.

PMID- 28455417
TI  - Predictive Genomic Analyses Inform the Basis for Vitamin Metabolism and
      Provisioning in Bacteria-Arthropod Endosymbioses.
AB  - The requirement of vitamins for core metabolic processes creates a unique set of
      pressures for arthropods subsisting on nutrient-limited diets. While
      endosymbiotic bacteria carried by arthropods have been widely implicated in
      vitamin provisioning, the underlying molecular mechanisms are not well
      understood. To address this issue, standardized predictive assessment of vitamin
      metabolism was performed in 50 endosymbionts of insects and arachnids. The
      results predicted that arthropod endosymbionts overall have little capacity for
      complete de novo biosynthesis of conventional or active vitamin forms. Partial
      biosynthesis pathways were commonly predicted, suggesting a substantial role in
      vitamin provisioning. Neither taxonomic relationships between host and symbiont,
      nor the mode of host-symbiont interaction were clear predictors of endosymbiont
      vitamin pathway capacity. Endosymbiont genome size and the synthetic capacity of
      nonsymbiont taxonomic relatives were more reliable predictors. We developed a new
      software application that also predicted that last-step conversion of
      intermediates into active vitamin forms may contribute further to vitamin
      biosynthesis by endosymbionts. Most instances of predicted vitamin conversion
      were paralleled by predictions of vitamin use. This is consistent with
      achievement of provisioning in some cases through upregulation of pathways that
      were retained for endosymbiont benefit. The predicted absence of other enzyme
      classes further suggests a baseline of vitamin requirement by the majority of
      endosymbionts, as well as some instances of putative mutualism. Adaptation of
      this workflow to analysis of other organisms and metabolic pathways will provide
      new routes for considering the molecular basis for symbiosis on a comprehensive
      scale.

PMID- 28455419
TI  - CXCL1 Is Critical for Premetastatic Niche Formation and Metastasis in Colorectal
      Cancer.
AB  - Emerging evidence suggests that the primary tumor influences the development of
      supportive metastatic microenvironments, referred to as premetastatic niches, in
      certain distant organs before arrival of metastatic cells. However, the
      mechanisms underlying the contributions of the primary tumor to premetastatic
      niche formation are not fully understood. Here, we demonstrate that colorectal
      carcinoma cells secrete VEGFA, which stimulates tumor-associated macrophages to
      produce CXCL1 in the primary tumor. Elevation of CXCL1 in premetastatic liver
      tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a
      premetastatic niche that ultimately promoted liver metastases. Importantly,
      premetastatic liver-infiltrating MDSCs induced tumor cell survival without
      involvement of innate or adaptive immune responses. Our study provides the first
      evidence that primary malignant cell-secreted VEGFA stimulates tumor-associated
      macrophages to produce CXCL1, which recruits CXCR2-positive MDSCs to form a
      premetastatic niche to promote liver metastases. Our findings not only shed light
      on how the tumor microenvironment contributes to premetastatic niche formation at
      distant sites, but they also provide comprehensive insights into how MDSCs are
      recruited to other organs where they contribute to metastatic spread of disease.
      Moreover, our work also provides a rationale for development of CXCR2 antagonists
      to inhibit or prevent metastatic spread of disease. Cancer Res; 77(13); 3655-65.
      (c)2017 AACR.

PMID- 28455420
TI  - Widespread Use of Misidentified Cell Line KB (HeLa): Incorrect Attribution and
      Its Impact Revealed through Mining the Scientific Literature.
AB  - Continuous cell lines are widely used, but can result in invalid, irreproducible
      research data. Cell line misidentification is a common problem that can be
      detected by authentication testing; however, misidentified cell lines continue to
      be used in publications. Here we explore the impact of one misidentified cell
      line, KB (HeLa), on the scientific literature. We identified 574 articles between
      2000 and 2014 that provided an incorrect attribution for KB, in accordance with
      its false identity as oral epidermoid carcinoma, but only 57 articles that
      provided a correct attribution for KB, as HeLa or cervical adenocarcinoma.
      Statistical analysis of 57 correct and 171 incorrect articles showed that the
      number of citations to these articles increased over time. Content analysis of
      200 citing articles showed there was a tendency to describe the cell line in
      accordance with the description in the cited paper. Analysis of journal impact
      factor showed no significant difference between correct and incorrect groups.
      Articles using KB or citing that usage were most frequently published in the
      subject areas of pharmacology, pharmacy, oncology, and medicinal chemistry. These
      findings are important for science policy and support the need for journals to
      require authentication testing as a condition of publication. Cancer Res; 77(11);
      2784-8. (c)2017 AACR.

PMID- 28455421
TI  - Therapeutic Rationale to Target Highly Expressed CDK7 Conferring Poor Outcomes in
      Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) patients commonly exhibit poor prognosis and
      high relapse after treatment, but there remains a lack of biomarkers and
      effective targeted therapies for this disease. Here, we report evidence
      highlighting the cell-cycle-related kinase CDK7 as a driver and candidate
      therapeutic target in TNBC. Using publicly available transcriptomic data from a
      collated set of TNBC patients (n = 383) and the METABRIC TNBC dataset (n = 217),
      we found CDK7 mRNA levels to be correlated with patient prognosis. High CDK7
      protein expression was associated with poor prognosis within the RATHER TNBC
      cohort (n = 109) and the METABRIC TNBC cohort (n = 203). The highly specific CDK7
      kinase inhibitors, BS-181 and THZ1, each downregulated CDK7-mediated
      phosphorylation of RNA polymerase II, indicative of transcriptional inhibition,
      with THZ1 exhibiting 500-fold greater potency than BS-181. Mechanistic
      investigations revealed that the survival of MDA-MB-231 TNBC cells relied heavily
      on the BCL-2/BCL-XL signaling axes in cells. Accordingly, we found that combining
      the BCL-2/BCL-XL inhibitors ABT-263/ABT199 with the CDK7 inhibitor THZ1
      synergized in producing growth inhibition and apoptosis of human TNBC cells.
      Collectively, our results highlight elevated CDK7 expression as a candidate
      biomarker of poor prognosis in TNBC, and they offer a preclinical proof of
      concept for combining CDK7 and BCL-2/BCL-XL inhibitors as a mechanism-based
      therapeutic strategy to improve TNBC treatment. Cancer Res; 77(14); 3834-45.
      (c)2017 AACR.

PMID- 28455422
TI  - Impact of RNA structure on ZFP36L2 interaction with luteinizing hormone receptor
      mRNA.
AB  - ZFP36L2 (L2) destabilizes AU-rich element (ARE)-containing transcripts and has
      been implicated in female fertility. We have shown that only one of three
      putative AREs within the 3' UTR of murine luteinizing hormone receptor mRNA,
      ARE2197 (UAUUUAU), is capable of interacting with L2. To assess whether
      structural elements of ARE2197 could explain this unique binding ability, we
      performed whole-transcript SHAPE-MaP (selective 2' hydroxyl acylation by primer
      extension-mutational profiling) of the full-length mLHR mRNA. The data revealed
      that the functional ARE2197 is located in a hairpin loop structure and most
      nucleotides are highly reactive. In contrast, each of the nonbinding AREs, 2301
      and 2444, contains only a pentamer AUUUA; and in ARE2301 much of the ARE sequence
      is poorly accessible. Because the functional mARE was also found to be conserved
      in humans at the sequence level (ARE 2223), we decided to investigate whether
      binding and structure are also preserved. Similar to mouse, only one ARE in hLHR
      mRNA is capable of binding to L2; and it is also located in a hairpin structure,
      based on our SHAPE-MaP data. To investigate the role of secondary structure in
      the binding, we mutated specific nucleotides in both functional AREs. Mutations
      in the flexible stem region proximal to the loop that enforce strong base
      pairing, drastically reduced L2 binding affinity; this confirms that the
      structural context is critical for L2 recognition of hARE2223. Collectively, our
      results suggest that a combination of minimal ARE sequence, placement of the ARE
      in a hairpin loop, and stem flexibility mediate high-affinity L2 binding to hLHR
      mRNA.

PMID- 28455423
TI  - Can care staff accurately assess health-related quality of life of care home
      residents? A secondary analysis of data from the OPERA trial.
AB  - OBJECTIVES: To compare assessments of health-related quality of life outcomes of
      care home residents reported by residents and care staff acting as proxies.
      DESIGN: Linear regression and bivariate modelling of paired assessments from care
      home residents and care staff. SETTING: 78 care homes in 2 regions in England.
      PARTICIPANTS: 556 care home residents aged 65 years or older and care staff. MAIN
      OUTCOME MEASURES: EQ-5D utility scores and responses to individual EQ-5D
      dimensions. RESULTS: The depression status, cognitive function, physical
      function, activities of daily living, social engagement, pain and dementia
      diagnosis of care home residents all predicted discrepancies in EQ-5D reporting.
      For residents with no depressive symptoms, care staff underestimated residents'
      mean EQ-5D utility score by 0.134 (95% CI 0.097 to 0.171) and for those with
      severe depressive symptoms they overstated mean utility scores by 0.222 (95% CI
      0.104 to 0.339). With increasing levels of pain in residents the care staff
      progressively estimated EQ-5D utilities above self-reported values; by 0.236 (95%
      CI 0.003 to 0.469) in those with the second highest pain scores. For those with
      no cognitive impairment, proxies overstated mean utility scores by 0.097 (95% CI
      0.049 to 0.146), while for those with severe cognitive impairment they
      underestimated mean utility scores by 0.192 (95% CI 0.143 to 0.241). CONCLUSIONS:
      Care home residents and staff appear to differ fundamentally in their assessment
      of the health-related quality of life, as measured by the EQ-5D, of residents
      with different levels of depression, pain and/or cognitive impairment. This could
      lead to interventions evaluated using proxy-based quality-adjusted life year
      estimates being wrongly rejected on cost-effectiveness grounds and may also make
      it difficult for carers to act as advocates with health and social care
      professionals for certain groups of residents. A more resident-focussed approach
      to assessment of health-related quality of life is needed.

PMID- 28455424
TI  - Accuracy of testing for anti-Helicobacter pylori IgG in urine for H. pylori
      infection diagnosis: a systematic review and meta-analysis.
AB  - OBJECTIVES: This meta-analysis aims to systematically measure the potential
      diagnostic value of anti-Helicobacter pylori IgG in urine for infection
      diagnosis, using all eligible studies published in English and Chinese languages.
      DESIGN: The random effect model was used to analyse the pooled sensitivity,
      specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic OR
      (DOR), together with the summary receiver operator characteristic curve. SETTING:
      Literature searches of databases including PubMed, EMBASE, MEDLINE, Web of
      Science, Chinese National Knowledge Infrastructure and Wanfang databases were
      performed to retrieve studies evaluating the diagnostic value of urine IgG
      antibody for H.pylori infection. PRIMARY OUTCOME MEASURE: Twenty-three studies
      with 4963 subjects were included in the current meta-analysis. RESULTS: The
      pooled sensitivity, specificity, PLR, NLR, DOR and area under the curve (AUC)
      were 0.83 (95% CI 0.82 to 0.85), 0.89 (95% CI 0.88 to 0.90), 8.81 (95% CI 6.37 to
      12.2), 0.13 (95% CI 0.09 to 0.2), 73 (95% CI 46.45 to 114.74) and 0.9551,
      respectively. Subgroup analyses showed that diagnostic accuracy of the urine IgG
      assay was no different in age, region, study population and assay method.
      CONCLUSIONS: Anti-H. pylori antibody in urine might serve as a good marker in
      diagnosing H. pylori infection. However, further validation based on a larger
      sample is still required.

PMID- 28455425
TI  - What is the difference between comprehensive and selective primary health care?
      Evidence from a five-year longitudinal realist case study in South Australia.
AB  - BACKGROUND: Since the WHO's Alma Ata Declaration on Primary Health Care (PHC)
      there has been debate about the advisability of adopting comprehensive or
      selective PHC. Proponents of the latter argue that a more selective approach will
      enable interim gains while proponents of a comprehensive approach argue that it
      is needed to address the underlying causes of ill health and improve health
      outcomes sustainably. METHODS: This research is based on four case studies of
      government-funded and run PHC services in Adelaide, South Australia. Program
      logic models were constructed from interviews and workshops. The initial model
      represented relatively comprehensive service provision in 2010. Subsequent
      interviews in 2013 permitted the construction of a selective PHC program logic
      model following a series of restructuring service changes. RESULTS: Comparison of
      the PHC service program logic models before and after restructuring illustrates
      the changes to the operating context, underlying mechanisms, service qualities,
      activities, activity outcomes and anticipated community health outcomes. The PHC
      services moved from focusing on a range of community, group and individual
      clinical activities to a focus on the management of people with chronic disease.
      Under the more comprehensive model, activities were along a continuum of
      promotive, preventive, rehabilitative and curative. Under the selective model,
      the focus moved to rehabilitative and curative with very little other activities.
      CONCLUSION: The study demonstrates the difference between selective and
      comprehensive approaches to PHC in a rich country setting and is useful in
      informing debates on PHC especially in the context of the Sustainable Development
      Goals.

PMID- 28455426
TI  - Essential components of integrated care for youth with mental health and
      addiction needs: protocol for a scoping review.
AB  - INTRODUCTION: Efforts to move towards integrated care have been met with
      increased interest and enthusiasm in recent years given the potential to improve
      care and population health while containing costs. However, there is a need to
      better understand community-based integrated care approaches for youth with
      mental health and/or addiction concerns to guide future implementation efforts
      and develop a set of standards for key components. The objectives of this scoping
      review are to: (1) identify the populations, settings, service providers,
      interventions, infrastructure and care coordination methods that have been
      included in integrated care for youth with mental health and/or addiction needs
      and (2) identify constructs that have been measured and evaluated (eg, outcomes,
      engagement) in the context of youth integrated care. METHODS AND ANALYSIS: Seven
      electronic databases and several grey literature sources will be searched for
      material from 2001 to 2016. Inclusion criteria will be broad with respect to type
      of work, as we will include all types of research studies as well as non-research
      studies that provide information relevant to characteristics and constructs
      measured in the context of integrated care for youth mental health. Titles and
      abstracts will be independently screened for eligibility by two raters using
      inclusion criteria. Full-text articles will then be accessed and independently
      screened for inclusion. A formal data extraction method will be employed,
      enabling synthesis of results in quantitative and qualitative formats. ETHICS AND
      DISSEMINATION: Results will be widely disseminated to various stakeholders to
      inform implementation and research efforts. Findings will also launch a Delphi
      method study leading to the development of an assessment tool for youth mental
      health services integration. This review does not require ethics approval.

PMID- 28455427
TI  - Geoffrey Munro Gill.

PMID- 28455428
TI  - Mortality studies for multiple sclerosis: still a useful tool to analyse long
      term outcome.

PMID- 28455429
TI  - MPs raise concern that health department is not prepared for Brexit negotiations.

PMID- 28455430
TI  - Endocrine targets of hypoxia-inducible factors.
AB  - Endocrine is an important and tightly regulated system for maintaining body
      homeostasis. Endocrine glands produce hormones, which are released into blood
      stream to guide the target cells responding to all sorts of stimulations. For
      maintaining body homeostasis, the secretion and activity of a particular hormone
      needs to be adjusted in responding to environmental challenges such as changes in
      nutritional status or chronic stress. Hypoxia, a status caused by reduced oxygen
      availability or imbalance of oxygen consumption/supply in an organ or within a
      cell, is a stress that affects many physiological and pathological processes.
      Hypoxic stress in endocrine organs is especially critical because endocrine
      glands control body homeostasis. Local hypoxia affects not only the particular
      gland but also the downstream cells/organs regulated by hormones secreted from
      this gland. Hypoxia-inducible factors (HIFs) are transcription factors that
      function as master regulators of oxygen homeostasis. Recent studies report that
      aberrant expression of HIFs in endocrine organs may result in the development
      and/or progression of diseases including diabetes, endometriosis, infertility and
      cancers. In this article, we will review recent findings in HIF-mediated
      endocrine organ dysfunction and the systemic syndromes caused by these disorders.

PMID- 28455431
TI  - Hypothalamic effects of neonatal diet: reversible and only partially leptin
      dependent.
AB  - Early life diet influences metabolic programming, increasing the risk for long
      lasting metabolic ill health. Neonatally overfed rats have an early increase in
      leptin that is maintained long term and is associated with a corresponding
      elevation in body weight. However, the immediate and long-term effects of
      neonatal overfeeding on hypothalamic anorexigenic pro-opiomelanocortin (POMC) and
      orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) circuitry, and if
      these are directly mediated by leptin, have not yet been examined. Here, we
      examined the effects of neonatal overfeeding on leptin-mediated development of
      hypothalamic POMC and AgRP/NPY neurons and whether these effects can be
      normalised by neonatal leptin antagonism in male Wistar rats. Neonatal
      overfeeding led to an acute (neonatal) resistance of hypothalamic neurons to
      exogenous leptin, but this leptin resistance was resolved by adulthood. While
      there were no effects of neonatal overfeeding on POMC immunoreactivity in
      neonates or adults, the neonatal overfeeding-induced early increase in arcuate
      nucleus (ARC) AgRP/NPY fibres was reversed by adulthood so that neonatally
      overfed adults had reduced NPY immunoreactivity in the ARC compared with
      controls, with no further differences in AgRP immunoreactivity. Short-term
      neonatal leptin antagonism did not reverse the excess body weight or
      hyperleptinaemia in the neonatally overfed, suggesting factors other than leptin
      may also contribute to the phenotype. Our findings show that changes in the
      availability of leptin during early life period influence the development of
      hypothalamic connectivity short term, but this is partly resolved by adulthood
      indicating an adaptation to the metabolic mal-programming effects of neonatal
      overfeeding.

PMID- 28455432
TI  - Skeletal energy homeostasis: a paradigm of endocrine discovery.
AB  - Throughout the last decade, significant developments in cellular, molecular and
      mouse models have revealed major endocrine functions of the skeleton. More recent
      studies have evolved the interplay between bone-specific hormones, the skeleton,
      marrow adipose tissue, muscle and the brain. This review focuses on literature
      from the last decade, addressing the endocrine regulation of global energy
      metabolism via the skeleton. In addition, we will highlight several recent
      studies that further our knowledge of new endocrine functions of some organs;
      explore remaining unanswered questions; and, finally, we will discuss future
      directions for this more complex era of bone biology research.

PMID- 28455433
TI  - AKT2 Regulates Pulmonary Inflammation and Fibrosis via Modulating Macrophage
      Activation.
AB  - Idiopathic pulmonary fibrosis (IPF) is a highly lethal pathological process that
      is characterized by inflammation, fibroblast accumulation, and excessive collagen
      deposition. Although AKT2-mediated signaling pathways modulate inflammatory
      responses, their role in IPF has not been defined. We report that AKT2 deficiency
      (Akt2-/-) protected against bleomycin-induced pulmonary fibrosis and
      inflammation. Adoptive transfer of wild-type macrophages or administration of IL
      13 to Akt2-/- mice could restore pulmonary fibrosis. In response to IL-33
      treatment, Akt2-/- macrophages displayed decreased production of IL-13 and TGF
      beta1 and attenuated phosphorylation of FoxO3a compared with Akt2+/+ macrophages.
      Furthermore, the expression of IL-13 was increased by small interfering RNA
      knockdown of FoxO3a or in FoxO3a-deficient macrophages. By evaluating lung
      sections from pulmonary fibrosis patients, we found that the phosphorylation of
      AKT2 and FoxO3a was remarkably upregulated. Collectively, these results indicate
      that AKT2 modulates pulmonary fibrosis through inducing TGF-beta1 and IL-13
      production by macrophages, and inhibition of AKT2 may be a potential strategy for
      treating IPF.

PMID- 28455434
TI  - Oil-Soluble Contrast Medium (OSCM) for Hysterosalpingography Modulates Dendritic
      Cell and Regulatory T Cell Profiles in the Peritoneal Cavity: A Possible
      Mechanism by Which OSCM Enhances Fertility.
AB  - Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) is known to
      enhance fertility, although the mechanism is unclear. OSCM remains in the
      peritoneal cavity for several months after HSG. We hypothesized that OSCM that
      remains in the peritoneal cavity modulates dendritic cell (DC) and regulatory T
      cell (Treg) profiles and contributes to enhanced fertility. We characterized the
      profiles of DCs and Tregs in the peritoneal fluid from women who had undergone
      HSG. In vitro and in vivo effects of OSCM on monocyte-derived DCs and mouse
      peritoneal T cells were also evaluated. In comparison with women who have never
      experienced HSG, samples from women who had undergone HSG contained myeloid DCs
      with greater complexity and maturation, as well as had a marginally greater
      proportion of Tregs in their peritoneal fluid. OSCM is incorporated by monocyte
      derived DCs, which causes their maturation and contributes to the increase in
      Treg proportions. Samples from OSCM-injected mice contained greater proportions
      of Tregs in comparison with controls. These studies demonstrate that OSCM
      modulates T cell profiles that are compatible with the condition observed in
      women who have undergone HSG. This study demonstrates that exogenous lipids
      administered to the peritoneal cavity are incorporated by DCs and that they
      significantly alter the immune environment in the peritoneal cavity. This
      immunological impact may contribute to enhanced fertility and the development of
      alternative therapeutic strategies for managing other pathological conditions
      associated with immunological abnormalities in the peritoneal cavity.

PMID- 28455435
TI  - CD40L-Dependent Pathway Is Active at Various Stages of Rheumatoid Arthritis
      Disease Progression.
AB  - The inflammatory CD40-CD40L pathway is implicated in various autoimmune diseases,
      but the activity status of this pathway in various stages of rheumatoid arthritis
      (RA) progression is unknown. In this study, we used gene signatures of CD40L
      stimulation derived from human immature dendritic cells and naive B cells to
      assess the expression of CD40-downstream genes in synovial tissues from anti
      citrullinated protein Ab-positive arthralgia, undifferentiated arthritis (UA),
      early RA, and established RA cohorts in comparison with healthy donors.
      Interestingly, the expression of CD40LG and active full-length CD40 was increased
      in the disease tissues, whereas that of a dominant-negative CD40 isoform was
      decreased. Gene set variation analysis revealed that CD40L-responsive genes in
      immature dendritic cells and naive B cells were significantly enriched in
      synovial tissues from UA, early RA, and established RA patients. Additionally,
      CD40L-induced naive B cell genes were also significantly enriched in synovial
      tissues from arthralgia patients. In our efforts to characterize downstream
      mediators of CD40L signaling, we have identified GPR120 and KDM6B as novel
      components of the pathway. In conclusion, our data suggest that therapeutic CD40
      CD40L blocking agents may prove efficacious not only in early and established RA,
      but also in inhibiting the progression of the disease from arthralgia or UA to
      RA.

PMID- 28455437
TI  - Working in bigger groups of practices must not sacrifice core values, GP leader
      warns.

PMID- 28455436
TI  - Egr2 and 3 Inhibit T-bet-Mediated IFN-gamma Production in T Cells.
AB  - T-bet is important for differentiation of cytotoxic CD8 and Th1 CD4 T cells. We
      have discovered that Egr2 and 3 are potent inhibitors of T-bet function in CD4
      and CD8 effector T cells. Egr2 and 3 were essential to suppress Th1
      differentiation in Th2 and Th17 conditions in vitro and also to control IFN-gamma
      producing CD4 and CD8 T cells in response to virus infection. Together with Egr2
      and 3, T-bet is induced in naive T cells by Ag stimulation, but Egr2 and 3
      expression was inhibited by Th1-inducing cytokines. We found that Egr2 and 3
      physically interact with the T-box domain of T-bet, blocking T-bet DNA binding
      and inhibiting T-bet-mediated production of IFN-gamma. Thus, Egr2 and 3 are
      antagonists of T-bet function in effector T cells and are important for the
      control of inflammatory responses of T cells.

PMID- 28455438
TI  - Infusion reactions during infliximab treatment are not associated with IgE anti
      infliximab antibodies.
AB  - OBJECTIVES: Controversy exists on the role of IgE antidrug antibodies (IgE-ADA)
      in infusion reactions (IR) on infliximab treatment, partly due to the lack of a
      positive control used for assay validation. We sought to (1) develop a robust
      assay to measure IgE-ADA, including a positive control, (2) determine the
      association between IgE-ADA and IR and (3) determine the incidence of IgE-ADA in
      infliximab treated patients. METHODS: A recombinant human IgE anti-infliximab
      monoclonal antibody was developed as standard and positive control. With this
      antibody, we set up a novel robust assay to measure IgE-ADA. IgE-ADA was
      determined in three retrospective cohorts (n=159) containing IR+ (n=37) and IR-
      (n=39), and longitudinal sera of 83 spondyloarthritis. RESULTS: IgE-ADA was found
      in 0/39 IR-, whereas 4/37 (11%) IR+ showed low levels (0.1-0.3 IU/mL, below the
      0.35 IU/mL threshold associated with elevated risk of allergic symptoms). All
      patients who were IgE-ADA positive also had (very) high IgG-ADA levels. The
      incidence of IgE-ADA in patients with infliximab-treated spondyloarthritis was
      estimated at less than approximately 1%. CONCLUSIONS: IgE-ADA is rarely detected
      in infliximab-treated patients. Moreover, the absence of IgE-ADA in the majority
      of IR+ patients suggests that IgE-ADA is not associated with infusion reactions.

PMID- 28455439
TI  - Cancer incidence attributable to excess body weight in Alberta in 2012.
AB  - BACKGROUND: Excess body weight has been consistently associated with colorectal,
      breast, endometrial, esophageal, gall bladder, pancreatic and kidney cancers. The
      objective of this analysis was to estimate the proportion of total and site
      specific cancers attributable to excess body weight in adults in Alberta in 2012.
      METHODS: We estimated the proportions of attributable cancers using population
      attributable risk. Risk estimates were obtained from recent meta-analyses, and
      exposure prevalence estimates were obtained from the Canadian Community Health
      Survey. People with a body mass index of 25.00-29.99 kg/m2 and of 30 kg/m2 or
      more were categorized as overweight and obese, respectively. RESULTS: About 14%
      47% of men and 9%-35% of women in Alberta were classified as either overweight or
      obese; the proportion increased with increasing age for both sexes. We estimate
      that roughly 17% and 12% of obesity-related cancers among men and women,
      respectively, could be attributed to excess body weight in Alberta in 2012. The
      heaviest absolute burden in terms of number of cases was seen for breast cancer
      among women and for colorectal cancer among men. Overall, about 5% of all cancers
      in adults in Alberta in 2012 were estimated to be attributable to excess body
      weight in 2000-2003. INTERPRETATION: Excess body weight contributes to a
      substantial proportion of cases of cancers associated with overweight and obesity
      annually in Alberta. Strategies to improve energy imbalance and reduce the
      proportion of obese and overweight Albertans may have a notable impact on cancer
      incidence in the future.

PMID- 28455440
TI  - Sperm in hot water: direct and indirect thermal challenges interact to impact on
      brown trout sperm quality.
AB  - Climate change alters the thermal habitat of aquatic species on a global scale,
      generating novel environmental challenges during all life stages, including
      reproduction. Changes in water temperature profoundly influence the performance
      of ectothermic aquatic organisms. This is an especially crucial issue for
      migratory fish, because they traverse multiple environments in order to
      reproduce. In externally fertilizing migratory fish, gametes are affected by
      water temperature indirectly, within the reproductive organ in which they are
      produced during migration, as well as directly, upon release into the surrounding
      medium at the spawning grounds. Both direct (after release) and indirect (during
      production) thermal impacts on gamete quality have been investigated, but never
      in conjunction. Here, we assessed the cumulative influence of temperature on
      brown trout, Salmo trutta, sperm quality during sperm production (male
      acclimation temperature) as well as upon release (sperm activation water
      temperature) on two consecutive dates during the brown trout spawning season.
      Early in the season, warm acclimation of males reduced their fertilization
      probability (lower sperm velocity) when compared with cold-acclimated males,
      especially when the activation water temperature was also increased beyond the
      thermal optimum (resulting in a lower proportion of motile sperm with lower
      velocity). Later in the season, sperm quality was unaffected by acclimation
      temperature and thermal sensitivity of sperm was reduced. These results give
      novel insights into the complex impacts of climate change on fish sperm, with
      implications for the reproduction and management of hatchery and wild trout
      populations in future climate scenarios.

PMID- 28455441
TI  - Avian thermoregulation in the heat: evaporative cooling in five Australian
      passerines reveals within-order biogeographic variation in heat tolerance.
AB  - Evaporative heat loss pathways vary among avian orders, but the extent to which
      evaporative cooling capacity and heat tolerance vary within orders remains
      unclear. We quantified the upper limits to thermoregulation under extremely hot
      conditions in five Australian passerines: yellow-plumed honeyeater (Lichenostomus
      ornatus; ~17 g), spiny-cheeked honeyeater (Acanthagenys rufogularis; ~42 g),
      chestnut-crowned babbler (Pomatostomus ruficeps; ~52 g), grey butcherbird
      (Cracticus torquatus; ~86 g) and apostlebird (Struthidea cinerea; ~118 g). At air
      temperatures (Ta) exceeding body temperature (Tb), all five species showed
      increases in Tb to maximum values around 44-45 degrees C, accompanied by rapid
      increases in resting metabolic rate above clearly defined upper critical limits
      of thermoneutrality and increases in evaporative water loss (EWL) to levels
      equivalent to 670-860% of baseline rates at thermoneutral Ta Maximum cooling
      capacity, quantified as the fraction of metabolic heat production dissipated
      evaporatively, ranged from 1.20 to 2.17, consistent with the known range for
      passerines, and well below the corresponding ranges for columbids and
      caprimulgids. Heat tolerance limit (HTL, the maximum Ta tolerated) scaled
      positively with body mass, varying from 46 degrees C in yellow-plumed honeyeaters
      to 52 degrees C in a single apostlebird, but was lower than that of three
      southern African ploceid passerines investigated previously. We argue this
      difference is functionally linked to a smaller scope for increases in EWL above
      baseline levels. Our data reiterate the reliance of passerines in general on
      respiratory evaporative heat loss via panting, but also reveal substantial within
      order variation in heat tolerance and evaporative cooling capacity.

PMID- 28455442
TI  - Increased mitochondrial energy efficiency in skeletal muscle after long-term
      fasting: its relevance to animal performance.
AB  - In the final stage of fasting, skeletal muscle mass and protein content
      drastically decrease when the maintenance of efficient locomotor activity becomes
      crucial for animals to reactivate feeding behaviour and survive a very long
      period of starvation. As mitochondrial metabolism represents the main
      physiological link between the endogenous energy store and animal performance,
      the aim of this study was to determine how a very long, natural period of fasting
      affected skeletal muscle mitochondrial bioenergetics in king penguin (Aptenodytes
      patagonicus) chicks. Rates of mitochondrial oxidative phosphorylation were
      measured in pectoralis permeabilized fibres and isolated mitochondria.
      Mitochondrial ATP synthesis efficiency and the activities of respiratory chain
      complexes were measured in mitochondria isolated from pectoralis muscle. Results
      from long-term (4-5 months) naturally fasted chicks were compared with those from
      short-term (10 day) fasted birds. The respiratory activities of muscle fibres and
      isolated mitochondria were reduced by 60% and 45%, respectively, on average in
      long-term fasted chicks compared with short-term fasted birds. Oxidative capacity
      and mitochondrial content of pectoralis muscle were lowered by long-term fasting.
      Bioenergetic analysis of pectoralis muscle also revealed that mitochondria were,
      on average, 25% more energy efficient in the final stage of fasting (4-5 months)
      than after 10 days of fasting (short-term fasted birds). These results suggest
      that the strong reduction in respiratory capacity of pectoralis muscle was partly
      alleviated by increased mitochondrial ATP synthesis efficiency. Such oxidative
      phosphorylation optimization can impact animal performance, e.g. the metabolic
      cost of locomotion or the foraging efficiency.

PMID- 28455443
TI  - Metalloriboswitches: RNA-based inorganic ion sensors that regulate genes.
AB  - Divalent ions fulfill essential cellular roles and are required for virulence by
      certain bacteria. Free intracellular Mg2+ can approach 5 mm, but at this level
      Mn2+, Ni2+, or Co2+ can be growth-inhibitory, and magnesium fluoride is toxic. To
      maintain ion homeostasis, many bacteria have evolved ion sensors embedded in the
      5'-leader sequences of mRNAs encoding ion uptake or efflux channels. Here, we
      review current insights into these "metalloriboswitches," emphasizing ion
      specific binding by structured RNA aptamers and associated conformational changes
      in downstream signal sequences. This riboswitch-effector interplay produces a
      layer of gene regulatory feedback that has elicited interest as an antibacterial
      target.

PMID- 28455444
TI  - Endophilin B2 facilitates endosome maturation in response to growth factor
      stimulation, autophagy induction, and influenza A virus infection.
AB  - Endocytosis, and the subsequent trafficking of endosomes, requires dynamic
      physical alterations in membrane shape that are mediated in part by endophilin
      proteins. The endophilin B family of proteins contains an N-terminal
      Bin/amphiphysin/Rvs (N-BAR) domain that induces membrane curvature to regulate
      intracellular membrane dynamics. Whereas endophilin B1 (SH3GLB1/Bif-1) is known
      to be involved in a number of cellular processes, including apoptosis, autophagy,
      and endocytosis, the cellular function of endophilin B2 (SH3GLB2) is not well
      understood. In this study, we used genetic approaches that revealed that
      endophilin B2 is not required for embryonic development in vivo but that
      endophilin B2 deficiency impairs endosomal trafficking in vitro, as evidenced by
      suppressed endosome acidification, EGFR degradation, autophagic flux, and
      influenza A viral RNA nuclear entry and replication. Mechanistically, although
      the loss of endophilin B2 did not affect endocytic internalization and lysosomal
      function, endophilin B2 appeared to regulate the trafficking of endocytic
      vesicles and autophagosomes to late endosomes or lysosomes. Moreover, we also
      found that despite having an intracellular localization and tissue distribution
      similar to endophilin B1, endophilin B2 is dispensable for mitochondrial
      apoptosis. Taken together, our findings suggest that endophilin B2 positively
      regulates the endocytic pathway in response to growth factor signaling, autophagy
      induction, and viral entry.

PMID- 28455445
TI  - The soluble protease ADAMDEC1 released from activated platelets hydrolyzes
      platelet membrane pro-epidermal growth factor (EGF) to active high-molecular
      weight EGF.
AB  - Platelets are the sole source of EGF in circulation, yet how EGF is stored or
      released from stimulated cells is undefined. In fact, we found platelets did not
      store EGF, synthesized as a single 6-kDa domain in pro-EGF, but rather expressed
      intact pro-EGF precursor on granular and plasma membranes. Activated platelets
      released high-molecular-weight (HMW)-EGF, produced by a single cleavage between
      the EGF and the transmembrane domains of pro-EGF. We synthesized a fluorogenic
      peptide encompassing residues surrounding the putative sessile arginyl residue
      and found stimulated platelets released soluble activity that cleaved this pro
      EGF1020-1027 peptide. High throughput screening identified chymostatins,
      bacterial peptides with a central cyclic arginyl structure, as inhibitors of this
      activity. In contrast, the matrix metalloproteinase/TACE (tumor necrosis factor
      alpha-converting enzyme) inhibitor GM6001 was ineffective. Stimulated platelets
      released the soluble protease ADAMDEC1, recombinant ADAMDEC1 hydrolyzed pro
      EGF1020-1027, and this activity was inhibited by chymostatin and not GM6001.
      Biotinylating platelet surface proteins showed ADAMDEC1 hydrolyzed surface pro
      EGF to HMW-EGF that stimulated HeLa EGF receptor (EGFR) reporter cells and EGFR
      dependent tumor cell migration. This proteolysis was inhibited by chymostatin and
      not GM6001. Metabolizing pro-EGF Arg1023 to citrulline with recombinant
      polypeptide arginine deiminase 4 (PAD4) abolished ADAMDEC1-catalyzed pro-EGF1020
      1027 peptidolysis, while pretreating intact platelets with PAD4 suppressed
      ADAMDEC1-, thrombin-, or collagen-induced release of HMW-EGF. We conclude that
      activated platelets release ADAMDEC1, which hydrolyzes pro-EGF to soluble HMW
      EGF, that HMW-EGF is active, that proteolytic cleavage of pro-EGF first occurs at
      the C-terminal arginyl residue of the EGF domain, and that proteolysis is the
      regulated and rate-limiting step in generating soluble EGF bioactivity from
      activated platelets.

PMID- 28455446
TI  - Enterovirus 71 suppresses interferon responses by blocking Janus kinase
      (JAK)/signal transducer and activator of transcription (STAT) signaling through
      inducing karyopherin-alpha1 degradation.
AB  - Enterovirus 71 (EV71) has emerged as one of the most important enteroviruses
      since the eradication of poliovirus, and it causes severe neurological symptoms
      for which no effective antiviral drugs are available. Type I interferons (IFN)
      alpha/beta have been used clinically as antiviral therapy as the first line of
      defense against virus infections successfully for decades. However, treatment
      with type I interferons has not been effective in patients with EV71 infection.
      In this study, we found that in cells pretreated with IFN-beta, EV71 infection
      could still lead to a cytopathic effect, and the viral replication was not
      affected. The mechanism by which EV71 antagonizes interferon signaling, however,
      has been controversial. Our study indicated that EV71 infection did not inhibit
      phosphorylation of STAT1/2 induced by IFN-beta stimulation, but p-STAT1/2
      transport into the nucleus was significantly blocked. We showed that EV71
      infection reduced the formation of STAT/karyopherin-alpha1 (KPNA1) complex upon
      interferon stimulation and that the virus down-regulated the expression of KPNA1,
      a nuclear localization signal receptor for p-STAT1. Using specific caspase
      inhibitors and siRNA for caspase-3, we demonstrated that EV71 infection induced
      degradation of cellular KPNA1 in a caspase-3-dependent manner, which led to
      decreased induction of interferon-inducible genes and IFN response. Viral 2A and
      3C proteases did not degrade KPNA1, inhibit the activity of ISRE or suppress the
      transcription of interferon-inducible genes induced by IFN-beta. Our study
      demonstrates a novel mechanism by which antiviral signaling is suppressed through
      degradation of KPNA1 by activated caspase-3 induced in an enteroviral infection.

PMID- 28455447
TI  - Acetylation of lysine epsilon-amino groups regulates aminoacyl-tRNA synthetase
      activity in Escherichia coli.
AB  - Previous proteomic analyses have shown that aminoacyl-tRNA synthetases in many
      organisms can be modified by acetylation of Lys. In this present study, leucyl
      tRNA synthetase and arginyl-tRNA synthetase from Escherichia coli (EcLeuRS and
      EcArgRS) were overexpressed and purified and found to be acetylated on Lys
      residues by MS. Gln scanning mutagenesis revealed that Lys619, Lys624, and Lys809
      in EcLeuRS and Lys126 and Lys408 in EcArgRS might play important roles in enzyme
      activity. Furthermore, we utilized a novel protein expression system to obtain
      enzymes harboring acetylated Lys at specific sites and investigated their
      catalytic activity. Acetylation of these Lys residues could affect their
      aminoacylation activity by influencing amino acid activation and/or the affinity
      for tRNA. In vitro assays showed that acetyl-phosphate nonenzymatically
      acetylates EcLeuRS and EcArgRS and suggested that the sirtuin class deacetylase
      CobB might regulate acetylation of these two enzymes. These findings imply a
      potential regulatory role for Lys acetylation in controlling the activity of
      aminoacyl-tRNA synthetases and thus protein synthesis.

PMID- 28455448
TI  - Molecular impact of covalent modifications on nonribosomal peptide synthetase
      carrier protein communication.
AB  - Nonribosomal peptide synthesis involves the interplay between covalent protein
      modifications, conformational fluctuations, catalysis, and transient protein
      protein interactions. Delineating the mechanisms involved in orchestrating these
      various processes will deepen our understanding of domain-domain communication in
      nonribosomal peptide synthetases (NRPSs) and lay the groundwork for the rational
      reengineering of NRPSs by swapping domains handling different substrates to
      generate novel natural products. Although many structural and biochemical studies
      of NRPSs exist, few studies have focused on the energetics and dynamics governing
      the interactions in these systems. Here, we present detailed binding studies of
      an adenylation domain and its partner carrier protein in apo-, holo-, and
      substrate-loaded forms. Results from fluorescence anisotropy, isothermal
      titration calorimetry, and NMR titrations indicated that covalent modifications
      to a carrier protein modulate domain communication, suggesting that chemical
      modifications to carrier proteins during NRPS synthesis may impart directionality
      to sequential NRPS domain interactions. Comparison of the structure and dynamics
      of an apo-aryl carrier protein with those of its modified forms revealed
      structural fluctuations induced by post-translational modifications and mediated
      by modulations of protein dynamics. The results provide a comprehensive molecular
      description of a carrier protein throughout its life cycle and demonstrate how a
      network of dynamic residues can propagate the molecular impact of chemical
      modifications throughout a protein and influence its affinity toward partner
      domains.

PMID- 28455450
TI  - Microvascular function in pre-eclampsia is influenced by insulin resistance and
      an imbalance of angiogenic mediators.
AB  - In preeclampsia, maternal microvascular function is disrupted and angiogenesis is
      dysfunctional. Insulin resistance that occurs in some pregnancies also
      pathologically affects microvascular function. We wished to examine the
      relationship of angiogenic mediators and insulin resistance on microvascular
      health in pregnancy. We performed a nested, case-control study of 16 women who
      developed preeclampsia with 17 normal pregnant controls. We hypothesized that the
      impaired microvascular blood flow in preeclamptic women associated with an
      increased ratio of the antiangiogenic factors; (s-endoglin [sEng] and soluble fms
      like tyrosine kinase-1 [sFlt-1]) and proangiogenic molecule (placental growth
      factor [PlGF]) could be influenced by insulin resistance. Serum samples taken
      after 28 weeks of gestation were measured for the angiogenic factors, insulin,
      and glucose alongside the inflammatory marker; tumor necrosis factor-alpha and
      endothelial activation, namely; soluble vascular cell adhesion molecule 1,
      intercellular adhesion molecule-1, and e-selectin. Maternal microvascular blood
      flow, measured by strain gauge plethysmography, correlated with ratios of pro-
      and antiangiogenic mediators independently of preeclampsia. Decreased
      microvascular function measured in preeclampsia strongly correlated with both the
      antiangiogenic factor (sFlt-1 + sEng): PlGF ratio and high levels of insulin
      resistance, and combining insulin resistance with antiangiogenic factor ratios
      further strengthened this relationship. In pregnancy, microvascular blood flow is
      strongly associated with perturbations in pro- and antiangiogenic mediators. In
      preeclampsia, the relationship of maternal microvascular dysfunction with
      antiangiogenic mediators is strengthened when combined with insulin resistance.

PMID- 28455449
TI  - Identification of a new small ubiquitin-like modifier (SUMO)-interacting motif in
      the E3 ligase PIASy.
AB  - Small ubiquitin-like modifier (SUMO) conjugation is a reversible post
      translational modification process implicated in the regulation of gene
      transcription, DNA repair, and cell cycle. SUMOylation depends on the sequential
      activities of E1 activating, E2 conjugating, and E3 ligating enzymes. SUMO E3
      ligases enhance transfer of SUMO from the charged E2 enzyme to the substrate. We
      have previously identified PIASy, a member of the Siz/protein inhibitor of
      activated STAT (PIAS) RING family of SUMO E3 ligases, as essential for mitotic
      chromosomal SUMOylation in frog egg extracts and demonstrated that it can mediate
      effective SUMOylation. To address how PIASy catalyzes SUMOylation, we examined
      various truncations of PIASy for their ability to mediate SUMOylation. Using NMR
      chemical shift mapping and mutagenesis, we identified a new SUMO-interacting
      motif (SIM) in PIASy. The new SIM and the currently known SIM are both located at
      the C terminus of PIASy, and both are required for the full ligase activity of
      PIASy. Our results provide novel insights into the mechanism of PIASy-mediated
      SUMOylation. PIASy adds to the growing list of SUMO E3 ligases containing
      multiple SIMs that play important roles in the E3 ligase activity.

PMID- 28455451
TI  - Long-term miR-29b suppression reduces aneurysm formation in a Marfan mouse model.
AB  - Aortic root aneurysm formation and subsequent dissection and/or rupture remain
      the leading cause of death in patients with Marfan syndrome. Our laboratory has
      reported that miR-29b participates in aortic root/ascending aorta extracellular
      matrix remodeling during early aneurysm formation in Fbn1C1039G/+ Marfan mice.
      Herein, we sought to determine whether miR-29b suppression can reduce aneurysm
      formation long-term. Fbn1C1039G/+ Marfan mice were treated with retro-orbital LNA
      anti-miR-29b inhibitor or scrambled-control-miR before aneurysms develop either
      (1) a single dose prenatally (pregnant Fbn1C1039G/+ mice at 14.5 days post
      coitum) (n = 8-10, each group) or (2) postnatally every other week, from 2 to 22
      weeks of age, and sacrificed at 24 weeks (n = 8-10, each group). To determine if
      miR-29b blockade was beneficial even after aneurysms develop, a third group of
      animals were treated every other week, starting at 8 weeks of age, until
      sacrificed (n = 4-6, each group). miR-29b inhibition resulted in aneurysm
      reduction, increased elastogenesis, decreased matrix metalloproteinase activity
      and decreased elastin breakdown. Prenatal LNA-anti-miR-29b inhibitor treatment
      decreased aneurysm formation up to age 32 weeks, whereas postnatal treatment was
      effective up to 16 weeks. miR-29b blockade did not slow aortic growth once
      aneurysms already developed. Systemic miR-29b inhibition significantly reduces
      aneurysm development long-term in a Marfan mouse model. Drug administration
      during aortic wall embryologic development appears fundamental. miR-29b
      suppression could be a potential therapeutic target for reducing aneurysm
      formation in Marfan syndrome patients.

PMID- 28455452
TI  - Corticospinal excitability to the biceps brachii and its relationship to
      postactivation potentiation of the elbow flexors.
AB  - We examined the effects of a submaximal voluntary elbow flexor contraction
      protocol on measures of corticospinal excitability and postactivation
      potentiation of evoked muscle forces and if these measures were state-dependent
      (rest vs. voluntary muscle contraction). Participants completed four experimental
      sessions where they rested or performed a 5% maximum voluntary contraction (MVC)
      of the elbow flexors prior to, immediately, and 5 min following a submaximal
      contraction protocol. During rest or 5% MVC, transcranial magnetic stimulation,
      transmastoid electrical stimulation, electrical stimulation of biceps brachii
      motor point and Erb's point were elicited to induce motor-evoked potentials
      (MEPs), cervicomedullary MEPs (CMEPs), potentiated twitch (PT) force, and maximal
      muscle compound action potential (Mmax), respectively prior to, immediately, and
      5 min postcontraction protocol. MEP amplitudes increased (215 and 165%Mmax, P <=
      0.03) only at 1 and 6s postcontraction protocol, respectively during rest but not
      5% MVC CMEP amplitudes decreased during rest and 5% MVC (range:21-58%Mmax, P <=
      0.04) for up to 81 sec postcontraction protocol. Peak twitch force increased
      immediately postcontraction protocol and remained elevated for 90 sec (range:122
      147% increase, P < 0.05). There was a significant positive correlation between
      MEP and PT force during rest (r = 0.88, P = 0.01) and a negative correlation
      between CMEP and PT force during rest (r = -0.85, P < 0.02 and 5% MVC (r = -0.96,
      P < 0.01) immediately postcontraction protocol. In conclusion, the change in
      corticospinal and spinal excitability was state- and time-dependent whereas
      spinal excitability and postactivation potentiation were time-dependent following
      the contraction protocol. Changes in corticospinal excitability and
      postactivation potentiation correlated and were also state-dependent.

PMID- 28455453
TI  - Short-term heat stress alters redox balance in porcine skeletal muscle.
AB  - Heat stress contributes to higher morbidity and mortality in humans and animals
      and is an agricultural economic challenge because it reduces livestock
      productivity. Redox balance and associated mitochondrial responses appear to play
      a central role in heat stress-induced skeletal muscle pathology. We have
      previously reported increased oxidative stress and mitochondrial content in
      oxidative muscle following 12 h of heat stress. The purposes of this
      investigation were to characterize heat stress-induced oxidative stress and
      changes in mitochondrial content and biogenic signaling in oxidative skeletal
      muscle. Crossbred gilts were randomly assigned to either thermal neutral (21
      degrees C; n = 8, control group) or heat stress (37 degrees C) conditions for 2 h
      (n = 8), 4 h (n = 8), or 6 h (n = 8). At the end, their respective environmental
      exposure, the red portion of the semitendinosus muscle (STR) was harvested. Heat
      stress increased concentration of malondialdehyde (MDA) following 2 and 4 h
      compared to thermal neutral and 6 h, which was similar to thermal neutral, and
      decreased linearly with time. Protein carbonyl content was not influenced by
      environment. Catalase activity was increased following 4 h of heat stress and
      superoxide dismutase activity was decreased following 6 h of heat stress compared
      to thermal neutral conditions. Heat stress-mediated changes in antioxidant
      activity were independent of altered protein abundance or transcript expression.
      Mitochondrial content and mitochondrial biogenic signaling were similar between
      groups. These data demonstrate that heat stress caused a transient increase in
      oxidative stress that was countered by a compensatory change in catalase
      activity. These findings contribute to our growing understanding of the
      chronology of heat stress-induced intracellular dysfunctions in skeletal muscle.

PMID- 28455455
TI  - Sexual healthcare must not be allowed to become "Cinderella" of NHS, warns royal
      college chair.

PMID- 28455454
TI  - Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic
      obstructive pulmonary disease.
AB  - RATIONALE: Cellular senescence is observed in the lungs of patients with COPD and
      may contribute to the disease pathogenesis. Growth differentiation factor 11
      (GDF11) belongs to the transforming growth factor beta superfamily and was
      recently reported to be a circulating protein that may have rejuvenating effects
      in mice. We aimed to investigate the amounts of GDF11 in the plasma and the lungs
      of patients with COPD and elucidate the possible roles of GDF11 in cellular
      senescence. METHODS: The plasma levels of GDF11 were investigated in two separate
      cohorts by western blotting. The localisation and expression of GDF11 in the
      lungs were investigated by immunohistochemistry and quantitative reverse
      transcription PCR, respectively. The effects of GDF11 on both cigarette smoke
      extract (CSE)-induced cellular senescence in vitro and on elastase-induced
      cellular senescence in vivo were investigated. RESULTS: The levels of plasma
      GDF11 in the COPD group were decreased compared with the control groups in the
      two independent cohorts. The levels of plasma GDF11 were significantly positively
      correlated with pulmonary function data. The mRNA expression of GDF11 in
      mesenchymal cells from the COPD group was decreased. Chronic exposure to CSE
      decreased the production of GDF11. Treatment with GDF11 significantly inhibited
      CSE-induced cellular senescence and upregulation of inflammatory mediators,
      partly through Smad2/3 signalling in vitro. Daily GDF11 treatment attenuated
      cellular senescence and airspace enlargement in an elastase-induced mouse model
      of emphysema. CONCLUSIONS: The decrease in GDF11 may be involved in the cellular
      senescence observed in COPD.

PMID- 28455456
TI  - Crohn's disease presenting as gastric outlet obstruction: a therapeutic
      challenge?
AB  - Isolated gastric Crohn's disease with initial presentation related to gastric
      outlet obstruction is an unusual clinicopathological entity. We undertake here a
      literature review of this rare initial presentation of isolated gastric Crohn's
      disease and discuss the formidable diagnostic and therapeutic challenges
      encountered in such patients.

PMID- 28455457
TI  - Odontogenic abscess mimicking acute dacryocystitis.
AB  - A middle-aged poorly controlled diabetic man developed left-sided orbital and
      facial swelling several days after extraction of a left upper wisdom tooth. The
      clinical impression was that of acute dacryocystitis. Opening the skin above the
      lacrimal sac failed to reveal an inflamed sac establishing the diagnosis of deep
      facial cellulitis. Complete resolution occurred few weeks after systemic
      antibiotics and repeated dental drainage of the tooth abscess.

PMID- 28455458
TI  - An interesting case of opium tea toxicity.
AB  - We present an unusual cause of respiratory arrest resulting from sole ingestion
      of home-brewed opium tea. A 64-year-old woman was found unresponsive and in
      respiratory arrest by a first responder. There were no obvious signs of regular
      recreational drug use. On presentation to the local district general hospital,
      the patient was in extremis, with severe physiological and biochemical
      derangements. A naloxone infusion was commenced and she later made a good
      recovery. It was subsequently discovered that she had brewed opium tea from opium
      buds she had picked from a nearby commercial poppy farm, a practice she had
      learnt while in Afghanistan.

PMID- 28455459
TI  - The use of CT angiography for preoperative evaluation of large foreign body
      retention following penetrating trauma.

PMID- 28455460
TI  - Erdheim-Chester disease associated with a novel, complex BRAF
      p.Thr599_Val600delinsArgGlu mutation.
AB  - BRAF mutation testing to determine eligibility for treatment with vemurafenib was
      performed on archival skin lesions of a 54-year-old patient diagnosed with
      Erdheim-Chester disease (ECD) in 1999. Sanger sequencing of DNA extracted from a
      2008 skin lesion identified two non-contiguous base substitutions in BRAF, which
      were shown by next-generation sequencing (NGS) to be located in the same allele.
      Due to its long-standing duration, molecular evolution of disease was possible;
      however, both Sanger and NGS of a 2000 skin lesion were unsuccessful due to the
      poor quality of DNA. Finally, droplet digital PCR using a probe specific for this
      novel mutation detected the complex BRAF mutation in both the 2000 and 2008
      lesions, indicating this case to be ECD with a novel underlying BRAF
      p.Thr599_Val600delinsArgGlu mutation. Although well at present, molecular
      modelling of the mutant BRAF suggests suboptimal binding of vemurafenib and hence
      reduced therapeutic effectiveness.

PMID- 28455461
TI  - A rare tumour of hand: angioleiomyoma.
AB  - Angioleiomyoma is a benign tumour composed of smooth muscle and vascular tissue.
      Because of the paucity of smooth muscles in the hand other than tunica media of
      the blood vessels, its occurrence is quite rare in the hand and only few cases
      are reported in the English literature. We present the case of a 49-year-old man
      with benign painless swelling on the dorsum of hand. Differential diagnosis of
      ganglion cyst and tendon sheath tumour were considered. However, excision biopsy
      revealed angioleiomyoma. At 2-year follow-up, the patient remained asymptomatic
      with no evidence of recurrence.

PMID- 28455462
TI  - Even the winners are losers.

PMID- 28455463
TI  - Becoming confident about confidence intervals.

PMID- 28455464
TI  - When is it safe to resume driving after total hip and total knee arthroplasty? a
      meta-analysis of literature on post-operative brake reaction times.
AB  - AIMS: The aim of this study was to assess the current available evidence about
      when patients might resume driving after elective, primary total hip (THA) or
      total knee arthroplasty (TKA) undertaken for osteoarthritis (OA). MATERIALS AND
      METHODS: In February 2016, EMBASE, MEDLINE, Web of Science, Scopus, Cochrane,
      PubMed Publisher, CINAHL, EBSCO and Google Scholar were searched for clinical
      studies reporting on 'THA', 'TKA', 'car driving', 'reaction time' and 'brake
      response time'. Two researchers (CAV and JJT) independently screened the titles
      and abstracts for eligibility and assessed the risk of bias. Both fixed and
      random effects were used to pool data and calculate mean differences (MD) and 95%
      confidence intervals (CI) between pre- and post-operative total brake response
      time (TBRT). RESULTS: A total of 19 studies were included. The assessment of the
      risk of bias showed that one study was at high risk, six studies at moderate risk
      and 12 studies at low risk. Meta-analysis of TBRT showed a MD decrease of 25.54
      ms (95% CI -32.02 to 83.09) two weeks after right-sided THA, and of 18.19 ms (95%
      CI -6.13 to 42.50) four weeks after a right-sided TKA, when compared with the pre
      operative value. CONCLUSION: The TBRT returned to baseline two weeks after a
      right-sided THA and four weeks after a right-sided TKA. These results may serve
      as guidelines for orthopaedic surgeons when advising patients when to resume
      driving. However, the advice should be individualised. Cite this article: Bone
      Joint J 2017;99-B:566-76.

PMID- 28455465
TI  - Vitamin E diffused highly cross-linked polyethylene in total hip arthroplasty at
      five years: a randomised controlled trial using radiostereometric analysis.
AB  - AIMS: The objective of this five-year prospective, blinded, randomised controlled
      trial (RCT) was to compare femoral head penetration into a vitamin E diffused
      highly cross-linked polyethylene (HXLPE) liner with penetration into a medium
      cross-linked polyethylene control liner using radiostereometric analysis.
      PATIENTS AND METHODS: Patients scheduled for total hip arthroplasty (THA) were
      randomised to receive either the study E1 (32 patients) or the control ArComXL
      polyethylene (35 patients). The median age (range) of the overall cohort was 66
      years (40 to 76). RESULTS: The five-year median (interquartile range) proximal
      femoral head penetration into the E1 was -0.05 mm (-0.13 to -0.02) and 0.07 mm (
      0.03 to 0.16) for ArComXL. At three and five years, the penetration was
      significantly greater in the ArComXL group compared with the E1 group (p = 0.029
      and p = 0.019, respectively). All patient-reported outcomes (PROs) improved
      significantly from the pre-operative interval compared with those at one year,
      and remained favourable at five years. There were no differences between the two
      groups at any interval. CONCLUSION: The five-year results showed that E1
      polyethylene does not wear more than the control, ArComXL. This is the longest
      term RCT comparing the wear performance and clinical outcome of vitamin E
      diffused HXLPE with a previous generation of medium cross-linked polyethylene.
      Cite this article: Bone Joint J 2017;99-B:577-84.

PMID- 28455466
TI  - Dislocation of a primary total hip arthroplasty is more common in patients with a
      lumbar spinal fusion.
AB  - AIMS: Lumbar fusion is known to reduce the variation in pelvic tilt between
      standing and sitting. A flexible lumbo-pelvic unit increases the stability of
      total hip arthroplasty (THA) when seated by increasing anterior clearance and
      acetabular anteversion, thereby preventing impingement of the prosthesis. Lumbar
      fusion may eliminate this protective pelvic movement. The effect of lumbar fusion
      on the stability of total hip arthroplasty has not previously been investigated.
      PATIENTS AND METHODS: The Medicare database was searched for patients who had
      undergone THA and spinal fusion between 2005 and 2012. PearlDiver software was
      used to query the database by the International Classification of Diseases, 9th
      Revision, Clinical Modification (ICD-9-CM) procedural code for primary THA and
      lumbar spinal fusion. Patients who had undergone both lumbar fusion and THA were
      then divided into three groups: 1 to 2 levels, 3 to 7 levels and 8+ levels of
      fusion. The rate of dislocation in each group was established using ICD-9-CM
      codes. Patients who underwent THA without spinal fusion were used as a control
      group. Statistical significant difference between groups was tested using the chi
      squared test, and significance set at p < 0.05. RESULTS: At one-year follow-up,
      14 747 patients were found to have had a THA after lumbar spinal fusion (12 079 1
      to 2 levels, 2594 3 to 7 levels, 74 8+ levels). The control group consisted of
      839 004 patients. The dislocation rate in the control group was 1.55%. A higher
      rate of dislocation was found in patients with a spinal fusion of 1 to 2 levels
      (2.96%, p < 0.0001) and 3 to 7 levels (4.12%, p < 0.0001). Patients with 3 to 7
      levels of fusion had a higher rate of dislocation than patients with 1 to 2
      levels of fusion (odds ratio (OR) = 1.60, p < 0.0001). When groups were matched
      for age and gender to the unfused cohort, patients with 1 to 2 levels of fusion
      had an OR of 1.93 (95% confidence interval (CI) 1.42 to 2.32, p < 0.001), and
      those with 3 to 7 levels of fusion an OR of 2.77 (CI 2.04 to 4.80, p < 0.001) for
      dislocation. CONCLUSION: Patients with a previous history of lumbar spinal fusion
      have a significantly higher rate of dislocation of their THA than age- and gender
      matched patients without a lumbar spinal fusion. Cite this article: Bone Joint J
      2017;99-B:585-91.

PMID- 28455467
TI  - Risk factors for failure of the 36 mm metal-on-metal Pinnacle total hip
      arthroplasty system: a retrospective single-centre cohort study.
AB  - AIMS: To determine ten-year failure rates following 36 mm metal-on-metal (MoM)
      Pinnacle total hip arthroplasty (THA), and identify predictors of failure.
      PATIENTS AND METHODS: We retrospectively assessed a single-centre cohort of 569
      primary 36 mm MoM Pinnacle THAs (all Corail stems) followed up since 2012
      according to Medicines and Healthcare Products Regulation Agency recommendations.
      All-cause failure rates (all-cause revision, and non-revised cross-sectional
      imaging failures) were calculated, with predictors for failure identified using
      multivariable Cox regression. RESULTS: Failure occurred in 97 hips (17.0%). The
      ten-year cumulative failure rate was 27.1% (95% confidence interval (CI) 21.6 to
      33.7). Primary implantation from 2006 onwards (hazard ratio (HR) 4.30; 95% CI
      1.82 to 10.1; p = 0.001) and bilateral MoM hip arthroplasty (HR 1.59; 95% CI 1.03
      to 2.46; p = 0.037) predicted failure. The effect of implantation year on failure
      varied over time. From four years onwards following surgery, hips implanted since
      2006 had significantly higher failure rates (eight years 28.3%; 95% CI 23.1 to
      34.5) compared with hips implanted before 2006 (eight years 6.3%; 95% CI 2.4 to
      15.8) (HR 15.2; 95% CI 2.11 to 110.4; p = 0.007). CONCLUSION: We observed that 36
      mm MoM Pinnacle THAs have an unacceptably high ten-year failure rate, especially
      if implanted from 2006 onwards or in bilateral MoM hip patients. Our findings
      regarding implantation year and failure support recent concerns about the device
      manufacturing process. We recommend all patients undergoing implantation since
      2006 and those with bilateral MoM hips undergo regular investigation, regardless
      of symptoms. Cite this article: Bone Joint J 2017;99-B:592-600.

PMID- 28455468
TI  - Radiographic scoring system for the evaluation of stability of cementless
      acetabular components in the presence of osteolysis.
AB  - AIMS: The stability of cementless acetabular components is an important factor
      for surgical planning in the treatment of patients with pelvic osteolysis after
      total hip arthroplasty (THA). However, the methods for determining the stability
      of the acetabular component from pre-operative radiographs remain controversial.
      Our aim was to develop a scoring system to help in the assessment of the
      stability of the acetabular component under these circumstances. PATIENTS AND
      METHODS: The new scoring system is based on the mechanism of failure of these
      components and the location of the osteolytic lesion, according to the DeLee and
      Charnley classification. Each zone is evaluated and scored separately. The sum of
      the individual scores from the three zones is reported as a total score with a
      maximum of 10 points. The study involved 96 revision procedures which were
      undertaken for wear or osteolysis in 91 patients between July 2002 and December
      2012. Pre-operative anteroposterior pelvic radiographs and Judet views were
      reviewed. The stability of the acetabular component was confirmed intra
      operatively. RESULTS: Intra-operatively, it was found that 64 components were
      well-fixed and 32 were loose. Mean total scores in the well-fixed and loose
      components were 2.9 (0 to 7) and 7.2 (1 to 10), respectively (p < 0.001). In hips
      with a low score (0 to 2), the component was only loose in one of 33 hips (3%).
      The incidence of loosening increased with increasing scores: in those with scores
      of 3 and 4, two of 19 components (10.5%) were loose; in hips with scores of 5 and
      6, eight of 19 components (44.5%) were loose; in hips with scores of 7 or 8, 13
      of 17 components (70.6%) were loose; and for hips with scores of 9 and 10, nine
      of nine components (100%) were loose. Receiver-operating-characteristic curve
      analysis demonstrated very good accuracy (area under the curve = 0.90, p <
      0.001). The optimal cutoff point was a score of >= 5 with a sensitivity of 0.79,
      and a specificity of 0.87. CONCLUSION: There was a strong correlation between the
      scoring system and the probability of loosening of a cementless acetabular
      component. This scoring system provides a clinically useful tool for pre
      operative planning, and the evaluation of the outcome of revision surgery for
      patients with loosening of a cementless acetabular component in the presence of
      osteolysis. Cite this article: Bone Joint J 2017;99-B:601-6.

PMID- 28455469
TI  - Management of massive acetabular bone defects in revision arthroplasty of the hip
      using a reconstruction cage and porous metal augment.
AB  - AIMS: It may not be possible to undertake revision total hip arthroplasty (THA)
      in the presence of massive loss of acetabular bone stock using standard
      cementless hemispherical acetabular components and metal augments, as
      satisfactory stability cannot always be achieved. We aimed to study the outcome
      using a reconstruction cage and a porous metal augment in these patients.
      PATIENTS AND METHODS: A total of 22 acetabular revisions in 19 patients were
      performed using a combination of a reconstruction cage and porous metal augments.
      The augments were used in place of structural allografts. The mean age of the
      patients at the time of surgery was 70 years (27 to 85) and the mean follow-up
      was 39 months (27 to 58). The mean number of previous THAs was 1.9 (1 to 3). All
      patients had segmental defects involving more than 50% of the acetabulum and
      seven hips had an associated pelvic discontinuity. RESULTS: Three failures were
      observed in two hips, both of which had undergone a previous resection of a
      tumour affecting the acetabulum. Other complications included a late arterial
      injury, a sciatic nerve palsy, a dislocation treated with a femoral revision, a
      deep infection treated with irrigation and debridement and a fracture of the
      greater trochanter treated conservatively. The mean Oxford Hip Score
      significantly increased from 13.9 (2 to 23) to 28.7 (13 to 38) (p < 0.00001). The
      mean vertical distance between the centre of rotation of the hip and its normal
      location decreased from 30 mm to 10 mm. CONCLUSIONS: Acceptable early
      survivorship can be achieved using this novel technique, but it may be unsuitable
      for use in patients who have previously undergone the resection of a tumour
      involving the acetabulum. Cite this article: Bone Joint J 2017;99-B:607-13.

PMID- 28455470
TI  - Functional outcome of debridement, antibiotics and implant retention in
      periprosthetic joint infection involving the hip: a case-control study.
AB  - AIMS: Advocates of debridement, antibiotics and implant retention (DAIR) in hip
      periprosthetic joint infection (PJI) argue that a procedure not disturbing a
      sound prosthesis-bone interface is likely to lead to better survival and
      functional outcome compared with revision. This case-control study aims were to
      compare outcome of DAIRs for infected primary total hip arthroplasty (THA) with
      outcomes following primary THA and two-stage revision of infected primary THAs.
      PATIENTS AND METHODS: We retrospectively reviewed all DAIRs, performed for
      confirmed infected primary hip arthropasty (n = 82) at out institution, between
      1997 and 2013. Data recorded included full patient information and type of
      surgery. Outcome measures included complications, mortality, implant survivorship
      and functional outcome. Outcome was compared with two control groups matched for
      gender and age; a cohort of primary THAs (n = 120) and a cohort of two-stage
      revisions for infection (n = 66). RESULTS: Mean age at DAIR was 69 years (33 to
      87) and mean follow-up was eight years (2 to 17; standard deviation (sd) 5). A
      total of 52 (63%) of DAIRs were for early PJI (less than six weeks). Greater
      success in the eradication of infection with DAIR was identified with early PJI,
      comprising an interval less than a week between onset of symptoms and exchange of
      modular components with the DAIR procedure. Eradication of infection,
      complications and re-operation rates were similar in the DAIR and two-stage
      revision groups. For hips with successful eradication of infection with DAIR, the
      five-year survival (98%; 95% confidence interval (CI) 94 to 100) was similar to
      the primary THA group (98%; 95% CI 95 to 100) (n = 43; p = 0.3). The DAIR group
      had inferior mean Oxford Hip Scores (OHS) (38; 12 to 48) compared with the
      primary THA group (42; 15 to 48) (p = 0.02) but a significantly better mean OHS
      compared with the two-stage revision group (31; 0 to 48) (p = 0.008). Patients
      who required only one DAIR for eradication of infection had a similar mean OHS
      (41; 20 to 48) to the primary THA group (p = 0.2). CONCLUSION: The DAIR procedure
      is associated with a similar complication rate and ability to eradicate infection
      as two-stage revision. This study emphasises the need for exchange of modular
      components for improved chances of eradication of infection. This is the first
      study showing that DAIR is better than a two-stage revision regarding functional
      outcome. Cite this article: Bone Joint J 2017;99-B:614-22.

PMID- 28455471
TI  - Five-year clinical and radiological outcomes in 257 consecutive cementless Oxford
      medial unicompartmental knee arthroplasties.
AB  - AIMS: Our aim was to examine the clinical and radiographic outcomes in 257
      consecutive Oxford unicompartmental knee arthroplasties (OUKAs) (238 patients),
      five years post-operatively. PATIENTS AND METHODS: A retrospective evaluation was
      undertaken of patients treated between April 2008 and October 2010 in a regional
      centre by two non-designing surgeons with no previous experience of UKAs. The
      Oxford Knee Scores (OKSs) were recorded and fluoroscopically aligned radiographs
      were assessed post-operatively at one and five years. RESULTS: The median age of
      the 238 patients was 65.0 years (interquartile range (IQR) 59.0 to 73.0), the
      median body mas index was 30.0 (IQR 27.5 to 33.0) and 51.7% were male. There were
      no intra-operative complications. There was a significant improvement in the
      median OKS at six weeks (34, IQR 31.0 to 37.0), one year (38, IQR 29.0 to 43.0)
      and five years (37, IQR 27.0 to 42.0) when compared with the pre-operative scores
      (16, IQR 13.0 to 19.0) (all p = < 0.01). No patient had progressive radiolucent
      lines or loosening. A total of 16 patients had died by five years. The cumulative
      survival at five years was 98.8% and the mean survival time was 5.8 years (95%
      confidence interval 5.6 to 5.9). A total of seven OUKAs (2.7%) were revised;
      three within five years and four thereafter, between 5.1 and 5.7 years post
      operatively. Five (1.9%) had re-operations within five years. CONCLUSION: The
      proportion of patients requiring revision at five years is lower than that
      generally reported for UKA. These findings add support for the use of the
      cementless OUKA outside the design centre. Longer follow-up is required. Cite
      this article: Bone Joint J 2017;99-B:623-31.

PMID- 28455472
TI  - Anterior knee pain and evidence of osteoarthritis of the patellofemoral joint
      should not be considered contraindications to mobile-bearing unicompartmental
      knee arthroplasty: a 15-year follow-up.
AB  - AIMS: It is not clear whether anterior knee pain and osteoarthritis (OA) of the
      patellofemoral joint (PFJ) are contraindications to medial unicompartmental knee
      arthroplasty (UKA). Our aim was to investigate the long-term outcome of a
      consecutive series of patients, some of whom had anterior knee pain and PFJ OA
      managed with UKA. PATIENTS AND METHODS: We assessed the ten-year functional
      outcomes and 15-year implant survival of 805 knees (677 patients) following
      medial mobile-bearing UKA. The intra-operative status of the PFJ was documented
      and, with the exception of bone loss with grooving to the lateral side, neither
      the clinical or radiological state of the PFJ nor the presence of anterior knee
      pain were considered a contraindication. The impact of radiographic findings and
      anterior knee pain was studied in a subgroup of 100 knees (91 patients). RESULTS:
      There was no relationship between functional outcomes, at a mean of ten years, or
      15-year implant survival, and pre-operative anterior knee pain, or the presence
      or degree of cartilage loss documented intra-operatively at the medial patella or
      trochlea, or radiographic evidence of OA in the medial side of the PFJ. In 6% of
      cases there was full thickness cartilage loss on the lateral side of the patella.
      In these cases, the overall ten-year function and 15-year survival was similar to
      those without cartilage loss; however they had slightly more difficulty with
      descending stairs. Radiographic signs of OA seen in the lateral part of the PFJ
      were not associated with a definite compromise in functional outcome or implant
      survival. CONCLUSION: Severe damage to the lateral side of the PFJ with bone loss
      and grooving remains a contraindication to mobile-bearing UKA. Less severe damage
      to the lateral side of the PFJ and damage to the medial side, however severe,
      does not compromise the overall function or survival, so should not be considered
      to be a contraindication. However, if a patient does have full thickness
      cartilage loss on the lateral side of the PFJ they may have a slight compromise
      in their ability to descend stairs. Pre-operative anterior knee pain also does
      not compromise the functional outcome or survival and should not be considered to
      be a contraindication. Cite this article: Bone Joint J 2017;99-B:632-9.

PMID- 28455473
TI  - Radiological and clinical comparison of kinematically versus mechanically aligned
      total knee arthroplasty.
AB  - AIMS: The aim of this study was to compare the post-operative radiographic and
      clinical outcomes between kinematically and mechanically aligned total knee
      arthroplasties (TKAs). PATIENTS AND METHODS: A total of 60 TKAs (30 kinematically
      and 30 mechanically aligned) were performed in 60 patients with varus
      osteoarthritis of the knee using a navigation system. The angles of orientation
      of the joint line in relation to the floor, the conventional and true mechanical
      axis (tMA) (the line from the centre of the hip to the lowest point of the
      calcaneus) were compared, one year post-operatively, on single-leg and double-leg
      standing long leg radiographs between the groups. The range of movement and 2011
      Knee Society Scores were also compared between the groups at that time. RESULTS:
      The angles of orientation of the joint line in the kinematic group changed from
      slight varus on double-leg standing to slight valgus with single-leg standing.
      The mechanical axes in the kinematic group passed through a neutral position of
      the knee in the true condition when the calcaneus was considered. The post
      operative angles of flexion and functional activity scores were significantly
      better in the kinematic than in the mechanical group (p < 0.003 and 0.03,
      respectively). CONCLUSION: A kinematically aligned TKA results in a joint line
      which has a more parallel orientation in relation to the floor during single- and
      double-leg standing, and more neutral weight-bearing in tMA than a mechanically
      aligned TKA. Cite this article: Bone Joint J 2017;99-B:640-6.

PMID- 28455474
TI  - Contemporary failure aetiologies of the primary, posterior-stabilised total knee
      arthroplasty.
AB  - AIMS: The number of revision total knee arthroplasties (TKA) that are performed
      is expected to increase. However, previous reports of the causes of failure after
      TKA are limited in that they report the causes at specific institutions, which
      are often dependent on referral patterns. Our aim was to report the most common
      indications for re-operations and revisions in a large series of posterior
      stabilised TKAs undertaken at a single institution, excluding referrals from
      elsewhere, which may bias the causes of failure. PATIENTS AND METHODS: A total of
      5098 TKAs which were undertaken between 2000 and 2012 were included in the study.
      Re-operations, revisions with modular component exchange, and revisions with non
      modular component replacement or removal were identified from the medical
      records. The mean follow-up was five years (two to 12). RESULTS: The Kaplan-Meier
      ten-year survival without a re-operation, modular component revision and non
      modular component revision was 95.7%, 99.3% and 95.3%, respectively. The most
      common indications for a re-operation were: post-operative stiffness (58%),
      delayed wound healing (21%), and patellar clunk (11%). The indications for
      isolated modular component revision were acute periprosthetic joint infection
      (PJI) (64%) and instability (36%). The most common indications for non-modular
      component revision were chronic PJI (52%), aseptic loosening (17%),
      periprosthetic fracture (10%), and instability (10%). CONCLUSION: Post-operative
      stiffness remains the most common indication for re-operation after TKA.
      Infection is the most common indication for modular and non-modular component
      revision. Aseptic loosening was not an uncommon cause of failure, however, it was
      much less common than in national registry and non-registry data. Focusing on
      posterior-stabilised TKAs initially performed at our institution allowed for an
      accurate assessment of the causes of failure in a contemporary specialty
      practice. Cite this article: Bone Joint J 2017;99-B:647-52.

PMID- 28455475
TI  - High failure rates in treatment of streptococcal periprosthetic joint infection:
      results from a seven-year retrospective cohort study.
AB  - AIMS: To investigate the outcomes of treatment of streptococcal periprosthetic
      joint infection (PJI) involving total knee and hip arthroplasties. PATIENTS AND
      METHODS: Streptococcal PJI episodes which occurred between January 2009 and
      December 2015 were identified from clinical databases. Presentation and clinical
      outcomes for 30 streptococcal PJIs in 30 patients (12 hip and 18 knee
      arthroplasties) following treatment were evaluated from the medical notes and at
      review. The Kaplan-Meier survival method was used to estimate the probability of
      infection-free survival. The influence of the biofilm active antibiotic rifampin
      was also assessed. RESULTS: The infection was thought to have been acquired
      haematogenously in 16 patients and peri-operatively in 14. The median follow-up
      time for successfully treated cases was 39.2 months (12 to 75), whereas failure
      of the treatment occurred within the first year following treatment on every
      occasion. The infection-free survival at three years with 12 patients at risk was
      59% (95% confidence interval 39% to 75%). Failure of the treatment was observed
      in ten of 22 PJIs (45%) treated with a two-stage revision arthroplasty, two of
      six (33%) treated by debridement and prosthesis retention, and in neither of the
      two PJIs treated with one-stage revision arthroplasty. Streptococcal PJI treated
      with or without rifampin included in the antibiotic regime showed no difference
      in treatment outcome (p = 0.175). CONCLUSION: The success of treatment of
      streptococcal PJI in our patient cohort was poor (18 of 30 cases, 59%). New
      therapeutic approaches for treating streptococcal PJI are needed. Cite this
      article: Bone Joint J 2017;99-B:653-9.

PMID- 28455476
TI  - Synovial calprotectin: a potential biomarker to exclude a prosthetic joint
      infection.
AB  - AIMS: Recently, several synovial biomarkers have been introduced into the
      algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin
      is a promising biomarker, with a high sensitivity and specificity, but it is
      expensive. Calprotectin is a protein that is present in the cytoplasm of
      neutrophils, is released upon neutrophil activation and exhibits anti-microbial
      activity. Our aim, in this study, was to determine the diagnostic potential of
      synovial calprotectin in the diagnosis of a PJI. PATIENTS AND METHODS: In this
      pilot study, we prospectively collected synovial fluid from the hip, knee,
      shoulder and elbow of 19 patients with a proven PJI and from a control group of
      42 patients who underwent revision surgery without a PJI. PJI was diagnosed
      according to the current diagnostic criteria of the Musculoskeletal Infection
      Society. Synovial fluid was centrifuged and the supernatant was used to measure
      the level of calprotectin after applying a lateral flow immunoassay. RESULTS: The
      median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to
      1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p <
      0.0001). Using a cut-off value of 50 mg/L, this level showed an excellent
      diagnostic accuracy, with an area under the curve of 0.94. The overall
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) was 89%, 90%, 81% and 95% respectively. The NPV was 97% in the nine
      patients with a chronic PJI. CONCLUSION: Synovial calprotectin may be a valuable
      biomarker in the diagnosis of a PJI, especially in the exclusion of an infection.
      With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be
      made. The measurement is cheap and is easy to use. Cite this article: Bone Joint
      J 2017;99-B:660-5.

PMID- 28455477
TI  - Long-term outcomes of cemented versus cementless humeral components in
      arthroplasty of the shoulder: a propensity score-matched analysis.
AB  - AIMS: In the initial development of total shoulder arthroplasty (TSA), the
      humeral component was usually fixed with cement. Cementless components were
      subsequently introduced. The aim of this study was to compare the long-term
      outcome of cemented and cementless humeral components in arthroplasty of the
      shoulder. PATIENTS AND METHODS: All patients who underwent primary arthroplasty
      of the shoulder at our institution between 1970 and 2012 were included in the
      study. There were 4636 patients with 1167 cemented humeral components and 3469
      cementless components. Patients with the two types of fixation were matched for
      nine different covariates using a propensity score analysis. A total of 551 well
      balanced pairs of patients with cemented and cementless components were available
      after matching for comparison of the outcomes. The clinical outcomes which were
      analysed included loosening of the humeral component determined at revision
      surgery, periprosthetic fractures, post-operative infection and operating time.
      RESULTS: The overall five-, ten-, 15- and 20-year rates of survival were 98.9%,
      97.2%, 95.5%, and 94.4%, respectively. Survival without loosening at 20 years was
      98% for cemented components and 92.4% for cementless components. After propensity
      score matching including fixation as determined by the design of the component,
      humeral loosening was also found to be significantly higher in the cementless
      group. Survival without humeral loosening at 20 years was 98.7% for cemented
      components and 91.0% for cementless components. There was no significant
      difference in the risk of intra- or post-operative fracture. The rate of survival
      without deep infection and the mean operating time were significantly higher in
      the cemented group. CONCLUSION: Both types of fixation give rates of long-term
      survival of > 90%. Cemented components have better rates of survival without
      loosening but this should be weighed against increased operating time and the
      risk of bony destruction of the proximal humerus at the time of revision of a
      cemented humeral component. Cite this article: Bone Joint J 2017;99-B:666-73.

PMID- 28455478
TI  - Early migration of a partially cemented fluted glenoid component inserted using a
      cannulated preparation system.
AB  - AIMS: Radiostereometric analysis (RSA) allows an extremely accurate measurement
      of early micromotion of components following arthroplasty. PATIENTS AND METHODS:
      In this study, RSA was used to measure the migration of 11 partially cemented
      fluted pegged glenoid components in patients with osteoarthritis who underwent
      total shoulder arthroplasty using an improved surgical technique (seven men, four
      women, mean age 68). Patients were evaluated clinically using the American
      Shoulder and Elbow Surgeons (ASES) and Constant-Murley scores and by CT scans two
      years post-operatively. RESULTS: There were two patterns of migration, the first
      showing little, if any, migration and the second showing rotation by > 6 degrees 
      as early as three months post-operatively. At two years, these two groups could
      be confirmed on CT scans, one with osseointegration around the central peg, and
      the second with cystic changes. Patients with osteolysis around the central peg
      were those with early migration and those with osseointegration had minimal early
      migration. Both groups,however,had similar clinical results. CONCLUSION: Rapid
      early migration associated with focal lucency and absence of osseointegration was
      observed in three of 11 glenoid components, suggesting that lack of initial
      stability leads to early movement and failure of osseointegration. Cite this
      article: Bone Joint J 2017;99-B:674-9.

PMID- 28455479
TI  - Induced membrane technique for treating tibial defects gives mixed results.
AB  - AIMS: This study describes the use of the Masquelet technique to treat segmental
      tibial bone loss in 12 patients. PATIENTS AND METHODS: This retrospective case
      series reviewed 12 patients treated between 2010 and 2015 to determine their
      clinical outcome. Patients were mostly male with a mean age of 36 years (16 to
      62). The outcomes recorded included union, infection and amputation. The mean
      follow-up was 675 days (403 to 952). RESULTS: The mean tibial defect measured 5.8
      cm (2 to 15) in length. Of the 12 patients, 11 had an open fracture. Eight
      underwent fixation with an intramedullary nail, three with plates and one with a
      Taylor Spatial Frame. The mean interval between stages was 57 days (35 to 89).
      Bony union was achieved in only five patients. Five patients experienced
      infective complications during treatment, with two requiring amputation because
      of severe infection. CONCLUSION: The Masquelet technique was relatively
      ineffective in achieving union in this series, and was associated with a high
      rate of infection. Cite this article: Bone Joint J 2017;99-B:680-5.

PMID- 28455480
TI  - The outcome of the surgical treatment of pelvic chondrosarcomas: a competing risk
      analysis of 58 tumours from a single centre.
AB  - AIMS: Few studies dealing with chondrosarcoma of the pelvis are currently
      available. Different data about the overall survival and prognostic factors have
      been published but without a detailed analysis of surgery-related complications.
      We aimed to analyse the outcome of a series of pelvic chondrosarcomas treated at
      a single institution, with particular attention to the prognostic factors. Based
      on a competing risk model, our objective was to identify risk factors for the
      development of complications. PATIENTS AND METHODS: In a retrospective single
      centre study, 58 chondrosarcomas (26 patients alive, 32 patients dead) of the
      pelvis were reviewed. The mean follow-up was 13 years (one week to 23.1 years).
      RESULTS: A total of 26 patients (45%) were alive and 32 patients (55%) had died.
      Overall survival was 76%, 55% and 45% at one, five and ten years post
      operatively, respectively. In a competing risk model the cumulative risk of the
      development of a surgery-related complication was 64% at six months and 69% at
      one year, post-operatively, respectively. Endoprosthetic reconstruction was a
      significant risk factor for the development of complications (p = 0.006).
      Complications were not significantly related to age or the location or grade of
      the tumour (p = 0.823, p = 0.976, p = 0.858). The development of complications
      did not have a negative effect on survival (p = 0.147). CONCLUSION: This is the
      first study with competing risk analysis of surgery-related complications in
      patients with a pelvic chondrosarcoma. The surgery in these patients remains
      prone to complications. Endoprosthetic reconstruction significantly increases the
      risk of the development of complications (p = 0.006). A competing risk model
      showed that the development of complications does not have a negative influence
      on overall survival (p = 0.147). An aggressive, surgical resection with the goal
      of achieving wide margins whenever possible remains the mainstay of treatment.
      Cite this article: Bone Joint J 2017;99-B:686-96.

PMID- 28455481
TI  - Use of inlet radiographs in the assessment of reduction after the surgical
      treatment of developmental dysplasia of the hip.
AB  - AIMS: This pilot study aimed to evaluate prospectively the use of inlet
      radiographs of the hip as an alternative method of the assessment of reduction
      after the surgical treatment of developmental dysplasia of the hip (DDH).
      PATIENTS AND METHODS: The children in this study underwent surgery between
      January 2013 and January 2015. All had inlet radiographs and CT scans post
      operatively. Data were analysed by determining inter-observer reliability and
      intra-observer reproducibility, using the kappa value (K). Differences were
      settled by discussion between the two observers until a consensus was reached.
      The sensitivity and specificity of the radiographic and CT results were compared.
      A total of 26 radiographs were obtained from 23 children, with a mean age of 2.38
      years (one to five). RESULTS: Similar high levels of intra- and inter-observer
      agreement were observed (K = 0.834, 95% confidence interval (CI)). There was a
      high agreement between the radiographic and CT results (K = 0.834, 5% CI), with
      excellent sensitivity and a specificity of 95.5%. CONCLUSION: These results
      suggest that inlet radiographs may be a reliable method of assessing the
      reduction of the hip after the surgical treatment of DDH. Cite this article: Bone
      Joint J 2017;99-B:697-701.

PMID- 28455482
TI  - Retraction: Post-operative neuropathy after total hip arthroplasty.
AB  - Post-operative neuropathy after total hip arthroplasty. Bone Joint J 2017;99-B:(1
      Supple A):46-49.This article is retracted at the request of the author. The paper
      contains data which forms part of a collaborative research effort at the author's
      institution. The data in this paper was used without the authority or permission
      of the co-authors. The data contained in the paper is at a preliminary stage and
      the author believes it unreliable. More robust statistical analysis has since
      been performed which has resulted in changes to the findings, for example the
      data in the paper was no adjusted for age or gender in the multivariate
      analysis.The author regrets any inconvenience and difficulties that this action
      may cause and apologise sincerely to the readers, reviewers, and editors of The
      Bone & Joint Journal

PMID- 28455483
TI  - Errata.
AB  - Khan OH, Malviya A, Subramanian P, Agolley D, Witt JD Minimally invasive
      periacetabular osteotomy using a modified Smith-Petersen approach. Bone Joint J
      2017;99-B:22-28.

PMID- 28455484
TI  - Errata.
AB  - Bsat S, Frei H, Beaule PE The acetabular labrum: review of its functionBone Joint
      J;2016;98-B:730-735.

PMID- 28455485
TI  - Errata.
AB  - De Martino I, D'Apolito R, Soranoglou VG, Poultsides LA, Sculco PK, Sculco TP.
      Dislocation following total hip arthroplasty using dual mobility acetabular
      components. Bone Joint J;2017;99-B:18-24.

PMID- 28455486
TI  - Errata.
AB  - van der Vegt AE, Grond R, Gruschke JS, Boomsma MF, Emmelot CH, Dijkstra PU, van
      der Sluis CK. The effect of two different orthoses on pain, hand function,
      patient satisfaction and preference in patients with thumb carpometacarpal
      osteoarthritis. Bone Joint J;2017;99-B:237-244.

PMID- 28455487
TI  - Errata.
AB  - Haefeli PC, Marecek GS, Keel MJB, Siebenrock KA, Tannast M. Patients undergoing
      surgical hip dislocation for the treatment of acetabular fractures show
      favourable long-term outcome. Bone Joint J;2017;99-B:508-515.

PMID- 28455488
TI  - Correction to: "The Cardenolide Glycoside Acovenoside A Affords Protective
      Activity in Doxorubicin-Induced Cardiotoxicity in Mice."

PMID- 28455489
TI  - ST-Segment Elevation Myocardial Infarction with Acute Stent Thrombosis Presenting
      as Intractable Hiccups: An Unusual Case.
AB  - BACKGROUND Acute coronary syndrome (ACS) can present with atypical chest pain or
      symptoms not attributed to heart disease, such as indigestion. Hiccups, a benign
      and self-limited condition, can become persistent or intractable with overlooked
      underlying etiology. There are various causes of protracted hiccups, including
      metabolic abnormalities, psychogenic disorders, malignancy, central nervous
      system pathology, medications, pulmonary disorders, or gastrointestinal
      etiologies. It is rarely attributed to cardiac disease. CASE REPORT We report a
      case of intractable hiccups in a 51-year-old male with cocaine related myocardial
      infarction (MI) before and after stent placement. Coronary angiogram showed in
      stent thrombosis of the initial intervention. Following thrombectomy, balloon
      angioplasty, and stent, the patient recovered well without additional episodes of
      hiccups. Although hiccups are not known to present with a predilection for a
      particular cause of myocardial ischemia, this case may additionally be explained
      by the sympathomimetic effects of cocaine, which lead to vasoconstriction of
      coronary arteries. CONCLUSIONS Hiccups associated with cardiac enzyme elevation
      and EKG ST-segment elevation before and after percutaneous coronary intervention
      (PCI) maybe a manifestation of acute MI with or without stent. The fact that this
      patient was a cocaine user may have contributed to the unique presentation.

PMID- 28455490
TI  - 1,25(OH)2D3 Protects Liver Fibrosis Through Decreasing the Generation of TH17
      Cells.
AB  - BACKGROUND The aim of this study was to study the effects of 1-alpha,25-dihydroxy
      cholecalcifero (1,25(OH)2D3) on liver fibrosis and the generation of Th17 cells
      in vivo and in vitro. MATERIAL AND METHODS Thirty C57 mice were randomly divided
      into control, model, and treatment groups. Hepatic fibrosis was induced by
      subcutaneous injection of CCl4. Liver fibrosis condition was evaluated through
      pathological inspection and blood biochemical examination of liver function.
      Immunohistochemical assays were used to detect the expression of alpha-SMA, TGF
      beta, and collagen I to observe hepatic stellate cell activation level. Flow
      cytometry, ELISA, and RT-PCR were performed to explore the association between
      1,25(OH)2D3 and Th17 cell differentiation. RESULTS Collagen I, TGF-beta, and
      alpha-SMA were decreased after 1,25(OH)2D3 treatment. Consistently, RORgammat
      mRNA and the rate of Th17 cells was significantly reduced after 1,25(OH)2D3
      treatment. In vitro, the proportion of Th17 cells was also obviously reduced in
      the 1,25(OH)2D3 group, and mRNA levels of IL-17A, IL-22, RORgammat, and RORa were
      significantly decrease in the 1,25(OH)2D3 group compared to the control group.
      CONCLUSIONS Treatment with 1,25(OH)2D3 can alleviate the damage caused by liver
      fibrosis. Experiments in vivo and in vitro showed that 1,25(OH)2D3 treatment
      deceased the rates of Th1 and Th17 cells and increased the rate of Th2 cells. The
      level of IL-17A, IL-22 and IFN-gamma were decreased, while the level of IL-4 was
      increased by the treatment of 1,25(OH)2D3.

PMID- 28455491
TI  - Melatonin and its metabolites protect human melanocytes against UVB-induced
      damage: Involvement of NRF2-mediated pathways.
AB  - Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as
      6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which
      further cause damage to the skin cells. Irradiation of cultured human melanocytes
      with UVB stimulated ROS production, which was reduced in cells treated with
      melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5
      methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5
      MT). Melatonin and its derivatives also stimulated the expression of NRF2
      (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and
      proteins that play an important role in cell protection from different damaging
      factors including UVB. Silencing of NRF2 using siRNA diminished the protective
      effects of melatonin, while the membrane melatonin receptors (MT1 or MT2) did not
      change the activities of either melatonin or its derivatives. Melatonin and its
      metabolites enhanced the DNA repair in melanocytes exposed to UVB and stimulated
      expression of p53 phosphorylated at Ser-15. In conclusion, melatonin and its
      metabolites protect melanocytes from UVB-induced DNA damage and oxidative stress
      through activation of NRF2-dependent pathways; these actions are independent of
      an effect on the classic membrane melatonin receptors. Thus, melatonin and its
      derivatives can serve as excellent protectors of melanocytes against UVB-induced
      pathology.

PMID- 28455492
TI  - Seasonal variations of leaf and canopy properties tracked by ground-based NDVI
      imagery in a temperate forest.
AB  - Changes in plant phenology affect the carbon flux of terrestrial forest
      ecosystems due to the link between the growing season length and vegetation
      productivity. Digital camera imagery, which can be acquired frequently, has been
      used to monitor seasonal and annual changes in forest canopy phenology and track
      critical phenological events. However, quantitative assessment of the structural
      and biochemical controls of the phenological patterns in camera images has rarely
      been done. In this study, we used an NDVI (Normalized Difference Vegetation
      Index) camera to monitor daily variations of vegetation reflectance at visible
      and near-infrared (NIR) bands with high spatial and temporal resolutions, and
      found that the infrared camera based NDVI (camera-NDVI) agreed well with the leaf
      expansion process that was measured by independent manual observations at Harvard
      Forest, Massachusetts, USA. We also measured the seasonality of canopy structural
      (leaf area index, LAI) and biochemical properties (leaf chlorophyll and nitrogen
      content). We found significant linear relationships between camera-NDVI and leaf
      chlorophyll concentration, and between camera-NDVI and leaf nitrogen content,
      though weaker relationships between camera-NDVI and LAI. Therefore, we recommend
      ground-based camera-NDVI as a powerful tool for long-term, near surface
      observations to monitor canopy development and to estimate leaf chlorophyll,
      nitrogen status, and LAI.

PMID- 28455493
TI  - Host-probiotic interaction: new insight into the role of the endocannabinoid
      system by in vivo and ex vivo approaches.
AB  - The endocannabinoid system plays an important role in regulating inflammation in
      several chronic or anomalous gut inflammatory diseases. In vivo and ex vivo
      studies showed that 30 days treatment with a probiotic mix activated the
      endocannabinoid system in zebrafish. These results highlight the potential of
      this probiotic mixture to regulate immune cell function, by inducing gene
      expression of toll-like receptors and other immune related molecules.
      Furthermore, TUNEL assay showed a decrease in the number of apoptotic cells, and
      this finding was supported by a reduction in pro-apoptotic factors and an
      increase in anti-apoptotic molecules. The results presented here strengthen the
      molecular mechanisms activated by probiotic mix controlling immune response and
      inflammation.

PMID- 28455494
TI  - Novel 1.5 GPa-strength with 50%-ductility by transformation-induced plasticity of
      non-recrystallized austenite in duplex steels.
AB  - Needs for steel designs of ultra-high strength and excellent ductility have been
      an important issue in worldwide automotive industries to achieve energy
      conservation, improvement of safety, and crashworthiness qualities. Because of
      various drawbacks in existing 1.5-GPa-grade steels, new development of formable
      cold-rolled ultra-high-strength steels is essentially needed. Here we show a
      plausible method to achieve ultra-high strengths of 1.0~1.5 GPa together with
      excellent ductility above 50% by actively utilizing non-recrystallization region
      and TRansformation-Induced Plasticity (TRIP) mechanism in a cold-rolled and
      annealed Fe-Mn-Al-C-based steel. We adopt a duplex microstructure composed of
      austenite and ultra-fine ferrite in order to overcome low-yield-strength
      characteristics of austenite. Persistent elongation up to 50% as well as ultra
      high yield strength over 1.4 GPa are attributed to well-balanced mechanical
      stability of non-crystallized austenite with critical strain for TRIP. Our
      results demonstrate how the non-recrystallized austenite can be a metamorphosis
      in 1.5-GPa-grade steel sheet design.

PMID- 28455495
TI  - Repeated inoculation of cattle rumen with bison rumen contents alters the rumen
      microbiome and improves nitrogen digestibility in cattle.
AB  - Future growth in demand for meat and milk, and the socioeconomic and
      environmental challenges that farmers face, represent a "grand challenge for
      humanity". Improving the digestibility of crop residues such as straw could
      enhance the sustainability of ruminant production systems. Here, we investigated
      if transfer of rumen contents from bison to cattle could alter the rumen
      microbiome and enhance total tract digestibility of a barley straw-based diet.
      Beef heifers were adapted to the diet for 28 days prior to the experiment. After
      46 days, ~70 percent of rumen contents were removed from each heifer and replaced
      with mixed rumen contents collected immediately after slaughter from 32 bison.
      This procedure was repeated 14 days later. Intake, chewing activity, total tract
      digestibility, ruminal passage rate, ruminal fermentation, and the bacterial and
      protozoal communities were examined before the first and after the second
      transfer. Overall, inoculation with bison rumen contents successfully altered the
      cattle rumen microbiome and metabolism, and increased protein digestibility and
      nitrogen retention, but did not alter fiber digestibility.

PMID- 28455496
TI  - On the pH Dependence of the Potential of Maximum Entropy of Ir(111) Electrodes.
AB  - Studies over the entropy of components forming the electrode/electrolyte
      interface can give fundamental insights into the properties of electrified
      interphases. In particular, the potential where the entropy of formation of the
      double layer is maximal (potential of maximum entropy, PME) is an important
      parameter for the characterization of electrochemical systems. Indeed, this
      parameter determines the majority of electrode processes. In this work, we
      determine PMEs for Ir(111) electrodes. The latter currently play an important
      role to understand electrocatalysis for energy provision; and at the same time,
      iridium is one of the most stable metals against corrosion. For the experiments,
      we used a combination of the laser induced potential transient to determine the
      PME, and CO charge-displacement to determine the potentials of zero total charge,
      (EPZTC). Both PME and EPZTC were assessed for perchlorate solutions in the pH
      range from 1 to 4. Surprisingly, we found that those are located in the potential
      region where the adsorption of hydrogen and hydroxyl species takes place,
      respectively. The PMEs demonstrated a shift by ~30 mV per a pH unit (in the RHE
      scale). Connections between the PME and electrocatalytic properties of the
      electrode surface are discussed.

PMID- 28455497
TI  - Decreased Circulating Levels of Dickkopf-1 in Patients with Exudative Age-related
      Macular Degeneration.
AB  - Aberrant activation of the Wnt/beta-catenin signaling pathway plays a pathogenic
      role in retinal inflammation and neovascularization. Here, we investigated
      whether circulating levels of Dickkopf-1 (DKK-1), a specific inhibitor of this
      pathway, are altered in patients with exudative age-related macular degeneration
      (AMD). Plasma was obtained from 128 patients with exudative AMD, 46 patients with
      atrophic AMD and 111 healthy controls. DKK-1 levels in plasma were measured using
      ELISA, and data analyzed with one-way ANOVA, logistic regression analysis and
      receiver-operating characteristic analysis (ROC). We found that DKK-1 levels were
      decreased in exudative AMD patients, compared with healthy controls (P < 0.001)
      and atrophic AMD patients (P < 0.001). The decrease was more prominent in
      patients with classic choroidal neovascularization (CNV) than those with occult
      CNV (P < 0.001). The odds ratio (OR) of exudative AMD was 11.71 (95% CI; 5.24
      6.13) for lowest versus upper quartile of DKK-1 levels. For discriminating
      exudative AMD patients, the optimum diagnostic cutoff of DKK-1 was 583.1 pg/mL
      with the area under curve (AUC) 0.76 (95% CI, 0.70-0.82; P < 0.001), sensitivity
      78.1% and specificity 63.1%. These findings suggested that decreased circulating
      DKK-1 levels are associated with the development and severity of exudative AMD,
      and have potential to become a biomarker for exudative AMD.

PMID- 28455498
TI  - Grb2 carboxyl-terminal SH3 domain can bivalently associate with two ligands, in
      an SH3 dependent manner.
AB  - Src homology domain containing leukocyte protein of 65 kDa (SLP65), the growth
      factor receptor binding protein 2 (Grb2), and the guanine nucleotide exchange
      factor for the Rho family GTPases (Vav), self associate in unstimulated B cells
      as components of the preformed B cell receptor transducer module, in an SH3
      dependent manner. The complex enables the B cell to promptly respond to BCR
      aggregation, resulting in signal amplification. It also facilitates Vav
      translocation to the membrane rafts, for activation. Here we uncover the
      molecular mechanism by which the complex may be formed in the B cell. The C
      terminal SH3 domain (SH3C) of Grb2 bivalently interacts with the atypical non
      PxxP proline rich region of SLP65, and the N-terminal SH3 domain (SH3N) of Vav,
      both the interactions crucial for the proper functioning of the B cell. Most
      surprisingly, the two ligands bind the same ligand binding site on the surface of
      Grb2 SH3C. Addition of SLP65 peptide to the Grb2-Vav complex abrogates the
      interaction completely, displacing Vav. However, the addition of Vav SH3N to the
      SLP65-Grb2 binary complex, results in a trimeric complex. Extrapolating these
      results to the in vivo conditions, Grb2 should bind the SLP65 transducer module
      first, and then Vav should associate.

PMID- 28455499
TI  - Families of stable solitons and excitations in the PT-symmetric nonlinear
      Schrodinger equations with position-dependent effective masses.
AB  - Since the parity-time-([Formula: see text]-) symmetric quantum mechanics was put
      forward, fundamental properties of some linear and nonlinear models with
      [Formula: see text]-symmetric potentials have been investigated. However,
      previous studies of [Formula: see text]-symmetric waves were limited to constant
      diffraction coefficients in the ambient medium. Here we address effects of
      variable diffraction coefficient on the beam dynamics in nonlinear media with
      generalized [Formula: see text]-symmetric Scarf-II potentials. The broken linear
      [Formula: see text] symmetry phase may enjoy a restoration with the growing
      diffraction parameter. Continuous families of one- and two-dimensional solitons
      are found to be stable. Particularly, some stable solitons are analytically
      found. The existence range and propagation dynamics of the solitons are
      identified. Transformation of the solitons by means of adiabatically varying
      parameters, and collisions between solitons are studied too. We also explore the
      evolution of constant-intensity waves in a model combining the variable
      diffraction coefficient and complex potentials with globally balanced gain and
      loss, which are more general than [Formula: see text]-symmetric ones, but feature
      similar properties. Our results may suggest new experiments for [Formula: see
      text]-symmetric nonlinear waves in nonlinear nonuniform optical media.

PMID- 28455500
TI  - Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast
      like cells.
AB  - Autophagy is a crucial and physiological process for cell survival from yeast to
      mammals, including protozoan parasites. Toxoplasma gondii, an intracellular
      parasite, typically exploits autophagic machinery of host cell; however host cell
      upregulates autophagy to combat the infection. Herein we tested the efficacy of
      Rottlerin, a natural polyphenol with autophagic promoting properties, against
      Toxoplasma infection on the chorioncarcinoma-derived cell line BeWo. We found
      that Rottlerin, at sub-toxic doses, induced morphological and biochemical
      alterations associated with autophagy and decreased Toxoplasma growth in infected
      cells. Although autophagy was synergically promoted by Toxoplasma infection in
      combination with Rottlerin treatment, the use of the autophagy inhibitor
      chloroquine revealed that Rottlerin anti-parasitic effect was largely autophagy
      independent and likely mediated by the converging inhibitory effect of Rottlerin
      and Toxoplasma in host protein translation, mediated by mTOR inhibition and
      eIF2alpha phosphorylation. Both events, which on one hand could explain the
      additive effect on autophagy induction, on the other hand led to inhibition of
      protein synthesis, thereby depriving Toxoplasma of metabolically essential
      components for multiplication. We suggest that modulation of the competition
      between pathogen requirement and host cell defense might be an attractive, novel
      therapeutic approach against Toxoplasma infection and encourage the development
      of Rottlerin-based new therapeutic formulations.

PMID- 28455502
TI  - Bio-Engineered Graphene-Based Cage for Efficient Local Enrichment and
      Biodegradation of Aqueous Organic Wastes.
AB  - Microorganism immobilization has attracted great attention as a traditional
      method to overcome aqueous organic wastes containing N, N-dimethylformamide
      (DMF). In this approach, graphene oxide was modified with functional polymer
      firstly to obtain micro-composites material (PGO), and then the prepared
      composites were deposited on the surface of copper mesh (CM) to block the meshes
      and CM@PGO was achieved. Moreover, cage-shaped model was designed based on CM@PGO
      and P. denitrificans was packed inside the cage for batch experiments. This
      strategy could enrich the local concentration of DMF due to the formation of
      hydrogen bonds with the oxygen-containing groups from PGO and the character of
      bacteria in captivity could also contribute to the process of degradation.
      Results showed that the approach could remove DMF more efficiently about 15%
      compared with free microorganism and presented excellent cycling performance.
      Meantime, physical adsorption and chemical adsorption were both contributed to
      the process of PGO adsorption, and the adsorption isotherm fits Langmuir model
      well, furthermore, the theoretical maximum of adsorption ability calculated
      through Langmuir model is 95 mg/g. In other words, this cage-shaped CM@PGO
      provided a facile platform for treating various wastewaters by altering the
      species of packed microorganisms, which exhibited considerable prospects for
      wastewater treatment.

PMID- 28455501
TI  - Structural alterations in the prefrontal cortex mediate the relationship between
      Internet gaming disorder and depressed mood.
AB  - Adaptive gaming use has positive effects, whereas depression has been reported to
      be prevalent in Internet gaming disorder (IGD). However, the neural correlates
      underlying the association between depression and Internet gaming remain unclear.
      Moreover, the neuroanatomical profile of the striatum in IGD is relatively less
      clear despite its important role in addiction. We found lower gray matter (GM)
      density in the left dorsolateral prefrontal cortex (DLPFC) in the IGD group than
      in the Internet gaming control (IGC) group and non-gaming control (NGC) group,
      and the GM density was associated with lifetime usage of Internet gaming,
      depressed mood, craving, and impulsivity in the gaming users. Striatal volumetric
      analysis detected a significant reduction in the right nucleus accumbens (NAcc)
      in the IGD group and its association with lifetime usage of gaming and
      depression. These findings suggest that alterations in the brain structures
      involved in the reward system are associated with IGD-related behavioral
      characteristics. Furthermore, the DLPFC, involved in cognitive control, was
      observed to serve as a mediator in the association between prolonged gaming and
      depressed mood. This finding may provide insight into an intervention strategy
      for treating IGD with comorbid depression.

PMID- 28455503
TI  - Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell
      precursors through FHOD1.
AB  - LINC complexes are crucial for the response of muscle cell precursors to the
      rigidity of their environment, but the mechanisms explaining this behaviour are
      not known. Here we show that pathogenic mutations in LMNA or SYNE-1 responsible
      for severe muscle dystrophies reduced the ability of human muscle cell precursors
      to adapt to substrates of different stiffness. Plated on muscle-like stiffness
      matrix, mutant cells exhibited contractile stress fibre accumulation, increased
      focal adhesions, and higher traction force than controls. Inhibition of Rho
      associated kinase (ROCK) prevented cytoskeletal defects, while inhibiting myosin
      light chain kinase or phosphorylation of focal adhesion kinase was ineffective.
      Depletion or inactivation of a ROCK-dependent regulator of actin remodelling, the
      formin FHOD1, largely rescued morphology in mutant cells. The functional
      integrity of lamin and nesprin-1 is thus required to modulate the FHOD1 activity
      and the inside-out mechanical coupling that tunes the cell internal stiffness to
      match that of its soft, physiological-like environment.

PMID- 28455504
TI  - Novel nano-semiconductor film layer supported nano-Pd Complex Nanostructured
      Catalyst Pd/F-MeOx/AC for High Efficient Selective Hydrogenation of Phenol to
      Cyclohexanone.
AB  - Supported metal as a type of heterogeneous catalysts are the most widely used in
      industrial processes. High dispersion of the metal particles of supported
      catalyst is a key factor in determining the performance of such catalysts. Here
      we report a novel catalyst Pd/F-MeOx/AC with complex nanostructured, Pd
      nanoparticles supported on the platelike nano-semiconductor film/activated
      carbon, prepared by the photocatalytic reduction method, which exhibited high
      efficient catalytic performance for selective hydrogenation of phenol to
      cyclohexanone. Conversion of phenol achieved up to more than 99% with a lower
      mole ratio (0.5%) of active components Pd and phenol within 2 h at 70  degrees C.
      The synergistic effect of metal nanoparticles and nano-semiconductors support
      layer and the greatly increasing of contact interface of nano-metal
      semiconductors may be responsible for the high efficiency. This work provides a
      clear demonstration that complex nanostructured catalysts with nano-metal and
      nano-semiconductor film layer supported on high specific surface AC can yield
      enhanced catalytic activity and can afford promising approach for developing new
      supported catalyst.

PMID- 28455505
TI  - APOE-E4 effects on longitudinal decline in olfactory and non-olfactory cognitive
      abilities in middle-aged and old adults.
AB  - Characterizing aging-related decline trajectories in mental abilities, and
      relationships of the E4 allele of the Apolipoprotein gene, helps to identify
      individuals at high risk for dementia. However, longitudinal changes in olfactory
      and non-olfactory cognitive abilities have not been investigated in relation to
      the E4 allele. In the present study, participants from a large population-based
      study (657 middle-aged and 556 old) were tested over 10 years on their
      performance on an odor identification task and three non-olfactory cognitive
      tasks; MMSE, episodic memory, and semantic memory. Our key finding is that in
      middle-aged participants, odor identification declined twice as fast for E4/4
      homozygotes, compared to non-carriers. However, in old participants, the E4/4
      homozygotes showed an impaired odor identification ability, but they declined at
      a similar rate as the non-carriers. Furthermore, in old participants all
      assessments displayed aging-related declines, but exaggerated declines in E4
      carriers were found only in MMSE and episodic memory assessments. In sum, we
      present evidence that odor identification ability starts to decline already in
      middle-aged, and that carriers of E4/4, who are at highest risk of developing
      dementia, decline twice as fast. Our results may have implications for use of
      odor identification assessment in detection of early-stage dementia.

PMID- 28455507
TI  - Importance of surface topography on pulsed laser-induced damage threshold of
      Sapphire crystals.
AB  - We measure the laser-induced damage threshold (LIDT) fluence under single shot at
      the surface of Sapphire samples prepared following the standards of two methods
      yielding to different surface finish and used in optical and laser industry. We
      use AFM microscopy to measure the roughness parameter Ra and power spectral
      density (PSD) of the sample surface. We show that the quality of surface
      topography resulting from surface preparation affects the damage threshold of
      Sapphire crystals exposed to femtosecond, picosecond, and nanosecond laser
      conditions at visible and near-infrared wavelengths. We observe a higher
      resistance to laser damage or macroscopic modification when the surface finish
      presents a smooth and regular topography. We indeed measure a 1.4 to 2 times
      increase of the LIDT fluence in femtosecond and picosecond regimes and up to 5
      times with nanosecond pulses. Using simple damage model and PSD data, we
      correlate the LIDT reduction of Sapphire samples of lower quality of surface
      finish with the high-frequency tail component of their PSD distribution
      corresponding to striations of the width of a fraction of the laser wavelength.
      This study emphasizes the importance of detailed assessment of surface topography
      for laser damage evaluation and understanding and for indicating directions of
      improvement.

PMID- 28455508
TI  - The paradox of a long grounding during West Antarctic Ice Sheet retreat in Ross
      Sea.
AB  - Marine geological data show that the West Antarctic Ice Sheet (WAIS) advanced to
      the eastern Ross Sea shelf edge during the Last Glacial Maximum (LGM) and
      eventually retreated ~1000 km to the current grounding-line position on the inner
      shelf. During the early deglacial, the WAIS deposited a voluminous stack of
      overlapping grounding zone wedges (GZWs) on the outer shelf of the Whales Deep
      Basin. The large sediment volume of the GZW cluster suggests that the grounding
      line position of the paleo-Bindschadler Ice Stream was relatively stationary for
      a significant time interval. We used an upper bound estimate of paleo-sediment
      flux to investigate the lower bound duration over which the ice stream would have
      deposited sediment to account for the GZW volume. Our calculations show that the
      cluster represents more than three millennia of ice-stream sedimentation. This
      long duration grounding was probably facilitated by rapid GZW growth. The
      subsequent punctuated large-distance (~200 km) grounding-line retreat may have
      been a highly non-linear ice sheet response to relatively continuous external
      forcing such as gradual climate warming or sea-level rise. These findings
      indicate that reliable predictions of future WAIS retreat may require
      incorporation of realistic calculations of sediment erosion, transport and
      deposition.

PMID- 28455506
TI  - Genome-wide fitness analyses of the foodborne pathogen Campylobacter jejuni in in
      vitro and in vivo models.
AB  - Campylobacter is the most common cause of foodborne bacterial illness worldwide.
      Faecal contamination of meat, especially chicken, during processing represents a
      key route of transmission to humans. There is a lack of insight into the
      mechanisms driving C. jejuni growth and survival within hosts and the
      environment. Here, we report a detailed analysis of C. jejuni fitness across
      models reflecting stages in its life cycle. Transposon (Tn) gene-inactivation
      libraries were generated in three C. jejuni strains and the impact on fitness
      during chicken colonisation, survival in houseflies and under nutrient-rich and 
      poor conditions at 4  degrees C and infection of human gut epithelial cells was
      assessed by Tn-insertion site sequencing (Tn-seq). A total of 331 homologous gene
      clusters were essential for fitness during in vitro growth in three C. jejuni
      strains, revealing that a large part of its genome is dedicated to growth. We
      report novel C. jejuni factors essential throughout its life cycle. Importantly,
      we identified genes that fulfil important roles across multiple conditions. Our
      comprehensive screens showed which flagella elements are essential for growth and
      which are vital to the interaction with host organisms. Future efforts should
      focus on how to exploit this knowledge to effectively control infections caused
      by C. jejuni.

PMID- 28455509
TI  - Three-stage anaerobic co-digestion of food waste and horse manure.
AB  - A novel compact three-stage anaerobic digester (HM3) was developed to combine the
      advantages of high solids anaerobic digestion (AD) and wet AD for co-digestion of
      food waste and horse manure. By having three separate chambers in the three-stage
      anaerobic digester, three different functional zones were created for high-solids
      hydrolysis, acidogenesis and wet methanogenesis. The results showed that the
      functionalized partitioning in HM3 significantly accelerated the solubilization
      of solid organic matters and the formation of volatile fatty acids, resulting in
      an increase of 11~23% in methane yield. VS reduction in the HM3 presents the
      highest rate of 71% compared to the controls. Pyrosequencing analysis indicated
      that different microbial communities in terms of hydrolyzing bacteria, acidogenic
      bacteria and methanogenic archaea were selectively enriched in the three separate
      chambers of the HM3. Moreover, the abundance of the methanogenic archaea was
      increased by 0.8~1.28 times compared to controls.

PMID- 28455510
TI  - Effects of fertilization on crop production and nutrient-supplying capacity under
      rice-oilseed rape rotation system.
AB  - Incredible accomplishments have been achieved in agricultural production in
      China, but many demanding challenges for ensuring food security and environmental
      sustainability remain. Field experiments were conducted from 2011-2013 at three
      different sites, including Honghu, Shayang, and Jingzhou in China, to determine
      the effects of fertilization on enhancing crop productivity and indigenous
      nutrient-supplying capacity (INuS) in a rice (Oryza sativa L.)-rapeseed (Brassica
      napus L.) rotation. Four mineral fertilizer treatments (NPK, NP, NK and PK) were
      applied in a randomized complete block design with three replicates. Crop yields
      were increased by 19-41% (rice) and 61-76% (rapeseed) during the two years of
      rice-rapeseed rotation under NPK fertilization compared to PK fertilization
      across the study sites. Yield responses to fertilization were ranked NPK > NP >
      NK > PK, illustrating that N deficiency was the most limiting condition in a rice
      rapeseed rotation, followed by P and K deficiencies. The highest and lowest N, P
      and K accumulations were observed under NPK and PK fertilization, respectively.
      The INuS of the soil decreased to a significant extent and affected rice-rapeseed
      rotation productivity at each site under NP, NK, and PK fertilization when
      compared to NPK. Based on the study results, a balanced nutrient application
      using NPK fertilization is a key management strategy for enhancing rice-rapeseed
      productivity and environmental safety.

PMID- 28455511
TI  - A microfabricated low-profile wideband antenna array for terahertz
      communications.
AB  - While terahertz communications are considered to be the future solutions for the
      increasing demands on bandwidth, terahertz equivalents of radio frequency front
      end components have not been realized. It remains challenging to achieve
      wideband, low profile antenna arrays with highly directive beams of radiation.
      Here, based on the complementary antenna approach, a wideband 2 * 2 cavity-backed
      slot antenna array with a corrugated surface is proposed. The approach is based
      on a unidirectional antenna with a cardiac radiation pattern and stable frequency
      characteristics that is achieved by integrating a series-resonant electric dipole
      with a parallel-resonant magnetic dipole. In this design, the slots work as
      magnetic dipoles while the corrugated surface radiates as an array of electric
      dipoles. The proposed antenna is realized at 1 THz operating frequency by
      stacking multiple metallized layers using the microfabrication technology. S
      parameter measurements of this terahertz low-profile metallic antenna array
      demonstrate high efficiency at terahertz frequencies. Fractional bandwidth and
      gain are measured to be 26% and 14 dBi which are consistent with the simulated
      results. The proposed antenna can be used as the building block for larger
      antenna arrays with more directive beams, paving the way to develop high gain low
      profile antennas for future communication needs.

PMID- 28455512
TI  - Systematic identification and characterization of cardiac long intergenic
      noncoding RNAs in zebrafish.
AB  - Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as
      potential key regulators of heart development and related diseases, but their
      identities and functions remain elusive. In this study, we sought to identify and
      characterize the cardiac lincRNA transcriptome in the experimentally accessible
      zebrafish model by integrating bioinformatics analysis with experimental
      validation. By conducting genome-wide RNA sequencing profiling of zebrafish
      embryonic hearts, adult hearts, and adult muscle, we generated a high-confidence
      set of 813 cardiac lincRNA transcripts, 423 of which are novel. Among these
      lincRNAs, 564 are expressed in the embryonic heart, and 730 are expressed in the
      adult heart, including 2 novel lincRNAs, TCONS_00000891 and TCONS_00028686, which
      exhibit cardiac-enriched expression patterns in adult heart. Using a method
      similar to a fetal gene program, we identified 51 lincRNAs with differential
      expression patterns between embryonic and adult hearts, among which
      TCONS_00009015 responded to doxorubicin-induced cardiac stress. In summary, our
      genome-wide systematic identification and characterization of cardiac lincRNAs
      lays the foundation for future studies in this vertebrate model to elucidate
      crucial roles for cardiac lincRNAs during heart development and cardiac diseases.

PMID- 28455514
TI  - Enterovirus D68 Subclade B3 Strain Circulating and Causing an Outbreak in the
      United States in 2016.
AB  - In 2014 the United States experienced a nationwide outbreak of Enterovirus D68
      (EV-D68) infection. There were no confirmed cases of EV-D68 in 2015 and CDC was
      only aware of limited sporadic EV-D68 detection in the US in 2016. In this
      report, we analyzed 749 nasopharyngeal (NP) specimens collected in 2015 and 2016
      from patients in the Lower Hudson Valley, New York using a previously validated
      EV-D68-specific rRT-PCR assay. EV-D68 was detected in none of 199 NP specimens
      collected in 2015, and in one of 108 (0.9%) samples from January to May and 159
      of 442 (36.0%) samples from July to October 2016. Complete EV-D68 genome
      sequences from 22 patients in 2016 were obtained using a metagenomic next
      generation sequencing assay. Comparative genome analysis confirmed that a new EV
      D68 strain belonging to subclade B3, with 3.2-4.8% divergence in nucleotide from
      subclade B1 strains identified during the 2014 US outbreak, was circulating in
      the US in 2016 and caused an outbreak in the Lower Hudson Valley, New York with
      160 laboratory-confirmed cases. Our data highlight the genetic variability and
      capacity in causing outbreak by diverse EV-D68 strains, and the necessity of
      awareness and more surveillance on their active circulation worldwide.

PMID- 28455513
TI  - Role of activating transcription factor 4 in the hepatic response to amino acid
      depletion by asparaginase.
AB  - : The anti-leukemic agent asparaginase activates the integrated stress response
      (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin
      complex 1 (mTORC1). The study objective was to investigate the protective role of
      activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome
      and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene
      expression patterns in livers from wildtype, Gcn2 -/-, and Atf4 -/- mice treated
      with asparaginase or excipient and further explored selected responses in livers
      from Atf4 +/- mice. Here, we show that ATF4 controls a hepatic gene expression
      profile that overlaps with GCN2 but is not required for downregulation of mTORC1
      during asparaginase. Ingenuity pathway analysis indicates GCN2 independently
      influences inflammation-mediated hepatic processes whereas ATF4 uniquely
      associates with cholesterol metabolism and endoplasmic reticulum (ER) stress.
      Livers from Atf4 -/- or Atf4 +/- mice displayed an amplification of the amino
      acid response and ER stress response transcriptional signatures. In contrast,
      reduction in hepatic mTORC1 signaling was retained in Atf4 -/- mice treated with
      asparaginase. CONCLUSIONS: GCN2 and ATF4 serve complementary roles in the hepatic
      response to asparaginase. GCN2 functions to limit inflammation and mTORC1
      signaling whereas ATF4 serves to limit the amino acid response and prevent ER
      stress during amino acid depletion by asparaginase.

PMID- 28455515
TI  - Mediastinal pulmonary artery is associated with greater artery diameter and
      lingular division volume.
AB  - Pulmonary vessels have numerous variation and aberrant branching patterns.
      Mediastinal lingular artery (MLA), the most common aberrant branch, might
      contribute to greater blood flow to lingular division. Hence, we investigated a
      correlation between lingular division volume and MLA using three-dimensional CT
      volumetry. We included 199 consecutive patients who underwent surveillance chest
      CT to detect possible malignancies in April 2015. We measured lingular division
      volume and cross-sectional area of lingular arteries using three-dimensional CT
      volumetry. MLA was identified in 58 cases (29.1%). The MLA group had
      significantly greater lingular division volume (median +/- quartile deviation:
      378.3 +/- 75.5 mL vs. 330.0 +/- 87.5 mL; p = 0.021) and percentage lingular
      division to left lung volume (19.0 +/- 2.62% vs. 16.6 +/- 2.39%; p < 0.001) than
      the non-MLA group. Total cross-sectional area of lingular arteries of the MLA
      group was significantly larger than that of the non-MLA group (46.1 +/- 9.46 vs.
      40.2 +/- 5.76 mm2; p = 0.003). The total cross-sectional area of the lingular
      arteries strongly correlated to the percentage of lingular division to left lung
      volume (r = 0.689, p < 0.001). This is the first report demonstrating a positive
      correlation between branching pattern of pulmonary artery and lung volume.

PMID- 28455516
TI  - Facile control of nanoporosity in Cellulose Acetate using Nickel(II) nitrate
      additive and water pressure treatment for highly efficient battery gel
      separators.
AB  - We succeed in fabricating nearly straight nanopores in cellulose acetate (CA)
      polymers for use as battery gel separators by utilizing an inorganic hexahydrate
      (Ni(NO3)2.6H2O) complex and isostatic water pressure treatment. The continuous
      nanopores are generated when the polymer film is exposed to isostatic water
      pressure after complexing the nickel(II) nitrate hexahydrate (Ni(NO3)2.6H2O) with
      the CA. These results can be attributed to the manner in which the polymer chains
      are weakened because of the plasticization effect of the Ni(NO3)2.6H2O that is
      incorporated into the CA. Furthermore, we performed extensive molecular dynamics
      simulation for confirming the interaction between electrolyte and CA separator.
      The well controlled CA membrane after water pressure treatment enables
      fabrication of highly reliable cell by utilizing 2032-type coin cell structure.
      The resulting cell performance exhibits not only the effect of the physical
      morphology of CA separator, but also the chemical interaction of electrolyte with
      CA polymer which facilitates the Li-ion in the cell.

PMID- 28455517
TI  - Neural Activity while Imitating Emotional Faces is Related to Both Lower and
      Higher-Level Social Cognitive Performance.
AB  - Imitation and observation of actions and facial emotional expressions activates
      the human fronto-parietal mirror network. There is skepticism regarding the role
      of this low-level network in more complex high-level social behaviour. We sought
      to test whether neural activation during an observation/imitation task was
      related to both lower and higher level social cognition. We employed an
      established observe/imitate task of emotional faces during functional MRI in 28
      healthy adults, with final analyses based on 20 individuals following extensive
      quality control. Partial least squares (PLS) identified patterns of relationships
      between spatial activation and a battery of objective out-of-scanner assessments
      that index lower and higher-level social cognitive performance, including the
      Penn emotion recognition task, reading the mind in the eyes, the awareness of
      social inference test (TASIT) parts 1, 2, and 3, and the relationships across
      domains (RAD) test. Strikingly, activity in limbic, right inferior frontal, and
      inferior parietal areas during imitation of emotional faces correlated with
      performance on emotion evaluation (TASIT1), social inference - minimal (TASIT2),
      social inference - enriched (TASIT3), and the RAD tests. These results show a
      role for this network in both lower-level and higher-level social cognitive
      processes which are collectively critical for social functioning in everyday
      life.

PMID- 28455518
TI  - Variability in bacterial flagella re-growth patterns after breakage.
AB  - Many bacteria swim through liquids or crawl on surfaces by rotating long
      appendages called flagella. Flagellar filaments are assembled from thousands of
      subunits that are exported through a narrow secretion channel and polymerize
      beneath a capping scaffold at the tip of the growing filament. The assembly of a
      flagellum uses a significant proportion of the biosynthetic capacities of the
      cell with each filament constituting ~1% of the total cell protein. Here, we
      addressed a significant question whether a flagellar filament can form a new cap
      and resume growth after breakage. Re-growth of broken filaments was visualized
      using sequential 3-color fluorescent labeling of filaments after mechanical
      shearing. Differential electron microscopy revealed the formation of new cap
      structures on broken filaments that re-grew. Flagellar filaments are therefore
      able to re-grow if broken by mechanical shearing forces, which are expected to
      occur frequently in nature. In contrast, no re-growth was observed on filaments
      that had been broken using ultrashort laser pulses, a technique allowing for very
      local damage to individual filaments. We thus conclude that assembly of a new cap
      at the tip of a broken filament depends on how the filament was broken.

PMID- 28455519
TI  - Calcium-Sensing Receptor Antagonist NPS 2143 Restores Amyloid Precursor Protein
      Physiological Non-Amyloidogenic Processing in Abeta-Exposed Adult Human
      Astrocytes.
AB  - Physiological non-amyloidogenic processing (NAP) of amyloid precursor holoprotein
      (hAPP) by alpha-secretases (e.g., ADAM10) extracellularly sheds
      neurotrophic/neuroprotective soluble (s)APPalpha and precludes amyloid-beta
      peptides (Abetas) production via beta-secretase amyloidogenic processing (AP).
      Evidence exists that Abetas interact with calcium-sensing receptors (CaSRs) in
      human astrocytes and neurons, driving the overrelease of toxic Abeta42/Abeta42-os
      (oligomers), which is completely blocked by CaSR antagonist (calcilytic) NPS
      2143. Here, we investigated the mechanisms underlying NPS 2143 beneficial effects
      in human astrocytes. Moreover, because Alzheimer's disease (AD) involves
      neuroinflammation, we examined whether NPS 2143 remained beneficial when both
      fibrillary (f)Abeta25-35 and a microglial cytokine mixture (CMT) were present.
      Thus, hAPP NAP prevailed over AP in untreated astrocytes, which extracellularly
      shed all synthesized sAPPalpha while secreting basal Abeta40/42 amounts.
      Conversely, fAbeta25-35 alone dramatically reduced sAPPalpha extracellular
      shedding while driving Abeta42/Abeta42-os oversecretion that CMT accelerated but
      not increased, despite a concurring hAPP overexpression. NPS 2143 promoted hAPP
      and ADAM10 translocation to the plasma membrane, thereby restoring sAPPalpha
      extracellular shedding and fully suppressing any Abeta42/Abeta42-os
      oversecretion, but left hAPP expression unaffected. Therefore, as anti-AD
      therapeutics calcilytics support neuronal viability by safeguarding astrocytes
      neurotrophic/neuroprotective sAPPalpha shedding, suppressing neurons and
      astrocytes Abeta42/Abeta42-os build-up/secretion, and remaining effective even
      under AD-typical neuroinflammatory conditions.

PMID- 28455520
TI  - A humanized mouse model identifies key amino acids for low immunogenicity of H7N9
      vaccines.
AB  - Influenza vaccines of H7N9 subtype are consistently less immunogenic in humans
      than vaccines developed for other subtypes. Although prior immunoinformatic
      analysis identified T-cell epitopes in H7 hemagglutinin (HA) which potentially
      enhance regulatory T cell response due to conservation with the human genome, the
      links between the T-cell epitopes and low immunogenicity of H7 HA remains unknown
      due to the lack of animal models reproducing the response observed in humans.
      Here, we utilized a humanized mouse model to recapitulate the low immunogenicity
      of H7 HA. Our analysis demonstrated that modification of a single H7 epitope by
      changing 3 amino acids so that it is homologous with a known H3 immunogenic
      epitope sequence significantly improved the immunogenicity of the H7 HA in the
      humanized mouse model, leading to a greater than 4-fold increase in HA-binding
      IgG responses. Thus, we provide experimental evidence for the important
      contribution of this H7-specific T cell epitope in determining the immunogenicity
      of an influenza vaccine. Furthermore, this study delineates strategies that can
      be used for screening and selecting vaccine strains using immunoinformatics tools
      and a humanized mouse model.

PMID- 28455521
TI  - Importance of the novel organic cation transporter 1 for tyrosine kinase
      inhibition by saracatinib in rheumatoid arthritis synovial fibroblasts.
AB  - Recent therapeutic approaches of rheumatoid arthritis (RA) address the use of
      small molecules such as tyrosine kinase inhibitors (TKIs). However, the TKIs
      developed to date have important side effects and/or scarce efficacy in
      inflammatory diseases such as RA. Since intracellular effective TKIs must enter
      the cell to reach their intracellular targets, here we investigated the
      interaction of the TKI saracatinib, a dual inhibitor of c-Src and c-Abl
      signaling, with transporters for organic cations as well as the role of these
      transporters for the biological effect of saracatinib in human RA-synovial
      fibroblasts (hRASF). Saracatinib significantly reduced proliferation of hRASF.
      The cellular saracatinib uptake was mainly dependent on the human novel organic
      cation transporter 1 (hOCTN1), which showed the highest apparent affinity for
      saracatinib among all other transporters for organic cations analyzed here. In
      hRASF, saracatinib biologic function was dependent on hOCTN1. Further analysis
      showed that disease specific factors (pH, inflammatory cytokines such as
      TNFalpha) regulated saracatinib uptake in hRASF. The knowledge of which
      transporters mediate the specific uptake of TKIs in target cells and of how the
      expression and function of such transporters are regulated in RA is of highest
      priority to develop effective drugs for successful therapy with minimal side
      effects.

PMID- 28455522
TI  - Genome of Paulownia (Paulownia fortunei) illuminates the related transcripts,
      miRNA and proteins for salt resistance.
AB  - Polyploidy in plants can bestow long-term evolutionary flexibility and resistance
      to biotic and abiotic stresses. The upstream activation mechanisms of salt
      response remain unknown. Here we integrated transcriptome, miRNA and proteome
      data to describe the link between abscisic acid (ABA)-effectors and salt
      resistance against the background of Paulownia genome. Combing GO and KEGG
      pathway annotation of differentially expressed genes and proteins, as well as
      differentially expressed miRNA, these results reflect endogenous signal ABA
      activate the downstream effectors, such as ion channel effectors and oxido
      reduction effectors, to maintain the homeostasis of Paulownia's growth. The
      cascaded metabolic network involved ABA biosynthesis, signaling transduction and
      the response of effectors. Our results will contribute to a comprehensive
      understanding of the genetic basis of salt tolerance, which may help to expand
      the available arable land for P. fortunei cultivation.

PMID- 28455523
TI  - Continuous daylight in the high-Arctic summer supports high plankton respiration
      rates compared to those supported in the dark.
AB  - Plankton respiration rate is a major component of global CO2 production and is
      forecasted to increase rapidly in the Arctic with warming. Yet, existing
      assessments in the Arctic evaluated plankton respiration in the dark. Evidence
      that plankton respiration may be stimulated in the light is particularly relevant
      for the high Arctic where plankton communities experience continuous daylight in
      spring and summer. Here we demonstrate that plankton community respiration
      evaluated under the continuous daylight conditions present in situ, tends to be
      higher than that evaluated in the dark. The ratio between community respiration
      measured in the light (Rlight) and in the dark (Rdark) increased as the 2/3 power
      of Rlight so that the Rlight:Rdark ratio increased from an average value of 1.37
      at the median Rlight measured here (3.62 umol O2 L-1 d-1) to an average value of
      17.56 at the highest Rlight measured here (15.8 umol O2 L-1 d-1). The role of
      respiratory processes as a source of CO2 in the Arctic has, therefore, been
      underestimated and is far more important than previously believed, particularly
      in the late spring, with 24 h photoperiods, when community respiration rates are
      highest.

PMID- 28455524
TI  - Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome
      are distinct from other RASopathy mouse models.
AB  - RASopathies, characterized by germline mutations in genes encoding proteins of
      the RAS-ERK signaling pathway, show overlapping phenotypes, which manifest
      themselves with a varying severity of intellectual disability. However, it is
      unclear to what extent they share the same downstream pathophysiology that
      underlies the cognitive deficits. Costello syndrome (CS) is a rare RASopathy
      caused by activating mutations in the HRAS gene. Here we investigated the
      mechanisms underlying the cognitive deficits of HRas G12V/G12V mice. HRas
      G12V/G12V mice showed robust upregulation of ERK signaling, neuronal hypertrophy,
      increased brain volume, spatial learning deficits, and impaired mGluR-dependent
      long-term depression (LTD). In contrast, long-term potentiation (LTP), which is
      affected in other RASopathy mouse models was unaffected. Treatment with
      lovastatin, a HMG-CoA-Reductase inhibitor which has been shown to rescue the
      behavioral phenotypes of mouse models of NF1 and Noonan syndrome, was unable to
      restore ERK signaling and the cognitive deficits of HRas G12V/G12V mice.
      Administration of a potent mitogen-activated protein kinase (MEK) inhibitor
      rescued the ERK upregulation and the mGluR-LTD deficit of HRas G12V/G12V mice,
      but failed to rescue the cognitive deficits. Taken together, this study indicates
      that the fundamental molecular and cellular mechanisms underlying the cognitive
      aspects of different RASopathies are remarkably distinct, and may require disease
      specific treatments.

PMID- 28455525
TI  - ER retention receptor, MoERR1 is required for fungal development and
      pathogenicity in the rice blast fungus, Magnaporthe oryzae.
AB  - ER retention receptor is a seven trans-membrane protein that plays pivotal roles
      in function and integrity of endoplasmic reticulum (ER). Insertional mutagenesis
      of Magnaporthe oryzae identified MoERR1 as a pathogenicity gene encoding putative
      ER retention receptor orthologous to ERD2 in Saccharomyces cerevisiae. Search
      through the genome identified that M. oryzae possesses another ortholog of ERD2,
      which is designated as MoERR2. When MoERR1 and MoERR2 were tagged with GFP, both
      were localized to ER. Targeted disruption of MoERR1 showed pleiotropic effects on
      phenotypes, while deletion of MoERR2 had no effect on phenotypes we examined. The
      disruption mutant of MoERR1 showed growth retardation and produced significantly
      reduced number of conidia with aberrant morphology. Appressoria from the mutant
      were unable to penetrate into plant tissues presumably due to defect in cell wall
      integrity, thereby rendering the mutant non-pathogenic. The MoERR1 mutant also
      appeared to display abnormal ER structure and mis-regulation of genes involved in
      chaperone function and unfolded protein response under ER stress condition. Taken
      together, these results suggest that MoERR1 is a ER retention receptor required
      for function and integrity of ER, and that MoERR1-mediated ER functionalities are
      essential for fungal development and pathogenesis.

PMID- 28455526
TI  - Genome editing in the mushroom-forming basidiomycete Coprinopsis cinerea,
      optimized by a high-throughput transformation system.
AB  - Mushroom-forming basidiomycetes produce a wide range of metabolites and have
      great value not only as food but also as an important global natural resource.
      Here, we demonstrate CRISPR/Cas9-based genome editing in the model species
      Coprinopsis cinerea. Using a high-throughput reporter assay with cryopreserved
      protoplasts, we identified a novel promoter, CcDED1 pro , with seven times
      stronger activity in this assay than the conventional promoter GPD2. To develop
      highly efficient genome editing using CRISPR/Cas9 in C. cinerea, we used the
      CcDED1 pro to express Cas9 and a U6-snRNA promoter from C. cinerea to express
      gRNA. Finally, CRISPR/Cas9-mediated GFP mutagenesis was performed in a stable GFP
      expression line. Individual genome-edited lines were isolated, and loss of GFP
      function was detected in hyphae and fruiting body primordia. This novel method of
      high-throughput CRISPR/Cas9-based genome editing using cryopreserved protoplasts
      should be a powerful tool in the study of edible mushrooms.

PMID- 28455527
TI  - Neural coding of prior expectations in hierarchical intention inference.
AB  - The ability to infer other people's intentions is crucial for successful human
      social interactions. Such inference relies on an adaptive interplay of sensory
      evidence and prior expectations. Crucially, this interplay would also depend on
      the type of intention inferred, i.e., on how abstract the intention is. However,
      what neural mechanisms adjust the interplay of prior and sensory evidence to the
      abstractness of the intention remains conjecture. We addressed this question in
      two separate fMRI experiments, which exploited action scenes depicting different
      types of intentions (Superordinate vs. Basic; Social vs. Non-social), and
      manipulated both prior and sensory evidence. We found that participants
      increasingly relied on priors as sensory evidence became scarcer. Activity in the
      medial prefrontal cortex (mPFC) reflected this interplay between the two sources
      of information. Moreover, the more abstract the intention to infer (Superordinate
      > Basic, Social > Non-Social), the greater the modulation of backward
      connectivity between the mPFC and the temporo-parietal junction (TPJ), resulting
      in an increased influence of priors over the intention inference. These results
      suggest a critical role for the fronto-parietal network in adjusting the relative
      weight of prior and sensory evidence during hierarchical intention inference.

PMID- 28455528
TI  - FlavonoidSearch: A system for comprehensive flavonoid annotation by mass
      spectrometry.
AB  - Currently, in mass spectrometry-based metabolomics, limited reference mass
      spectra are available for flavonoid identification. In the present study, a
      database of probable mass fragments for 6,867 known flavonoids (FsDatabase) was
      manually constructed based on new structure- and fragmentation-related rules
      using new heuristics to overcome flavonoid complexity. We developed the
      FlavonoidSearch system for flavonoid annotation, which consists of the FsDatabase
      and a computational tool (FsTool) to automatically search the FsDatabase using
      the mass spectra of metabolite peaks as queries. This system showed the highest
      identification accuracy for the flavonoid aglycone when compared to existing
      tools and revealed accurate discrimination between the flavonoid aglycone and
      other compounds. Sixteen new flavonoids were found from parsley, and the
      diversity of the flavonoid aglycone among different fruits and vegetables was
      investigated.

PMID- 28455529
TI  - Kanglaite sensitizes colorectal cancer cells to Taxol via NF-kappaBeta inhibition
      and connexin 43 upregulation.
AB  - Taxol, a first-line anti-tumour drug, has low effectiveness against colorectal
      cancer. Combination with other agents is an effective strategy to enhance Taxol
      cytotoxicity. Kanglaite injection is an extract from Coix lacryma-jobi seed and
      is usually combined with other agents to treat cancer. The aim of this study was
      to investigate the treatment effect of Taxol combined with Kanglaite on
      colorectal cancer cell lines. Kanglaite pretreatment followed by Taxol treatment
      was found to show the best synergism among all combination strategies. This
      combination also resulted in the smallest tumour volume in a Balb/c mice model.
      Kanglaite inhibited the expression of nuclear factor (NF)-kappaBeta and
      upregulated that of connexin 43, both of which sensitized cancer cells to Taxol.
      Moreover, Kanglaite increased many cellular variations caused by Taxol, including
      tubulin polymerization, caspase-3 cleavage, and upregulated expression of
      survivin and cyclin B1. These results suggest that Kanglaite pretreatment may
      increase the effect of Taxol on colorectal cancer.

PMID- 28455531
TI  - Temporal Characteristics of the Chinese Aviation Network and their Effects on the
      Spread of Infectious Diseases.
AB  - Aviation transportation systems have developed rapidly in recent years and have
      become a focus for research on the modeling of epidemics. However, despite the
      number of studies on aggregated topological structures and their effects on the
      spread of disease, the temporal sequence of flights that connect different
      airports have not been examined. In this study, to analyze the temporal pattern
      of the Chinese Aviation Network (CAN), we obtain a time series of topological
      statistics through sliding the temporal CAN with an hourly time window. In
      addition, we build two types of Susceptible-Infectious (SI) spreading models to
      study the effects of linking sequence and temporal duration on the spread of
      diseases. The results reveal that the absence of links formed by flights without
      alternatives at dawn and night causes a significant decrease in the
      centralization of the network. The temporal sparsity of linking sequence slows
      down the spread of disease on CAN, and the duration of flights intensifies the
      sensitiveness of CAN to targeted infection. The results are of great significance
      for further understanding of the aviation network and the dynamic process, such
      as the propagation of delay.

PMID- 28455530
TI  - NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent
      Manner in Systemic Lupus Erythematosus.
AB  - Systemic lupus erythematosus (SLE) features a decreased pool of CD4+CD25+Foxp3+ T
      regulatory (Treg) cells. We had previously observed NKG2D+CD4+ T cell expansion
      in contrast to a decreased pool of Treg cells in SLE patients, but whether
      NKG2D+CD4+ T cells contribute to the decreased Treg cells remains unclear. In the
      present study, we found that the NKG2D+CD4+ T cells efficiently killed NKG2D
      ligand (NKG2DL)+ Treg cells in vitro, whereby the surviving Treg cells in SLE
      patients showed no detectable expression of NKG2DLs. It was further found that
      MRL/lpr lupus mice have significantly increased percentage of NKG2D+CD4+ T cells
      and obvious decreased percentage of Treg cells, as compared with wild-type mice.
      Adoptively transferred NKG2DL+ Treg cells were found to be efficiently killed in
      MRL/lpr lupus mice, with NKG2D neutralization remarkably attenuating this
      killing. Anti-NKG2D or anti-interferon-alpha receptor (IFNAR) antibodies
      treatment in MRL/lpr mice restored Treg cells numbers and markedly ameliorated
      the lupus disease. These results suggest that NKG2D+CD4+ T cells are involved in
      the pathogenesis of SLE by killing Treg cells in a NKG2D-NKG2DL-dependent manner.
      Targeting the NKG2D-NKG2DL interaction might be a potential therapeutic strategy
      by which Treg cells can be protected from cytolysis in SLE patients.

PMID- 28455532
TI  - Left Ventricular Stiffness in Adolescents and Young Adults with Repaired
      Tetralogy of Fallot.
AB  - Left ventricular (LV) remodeling after tetralogy of Fallot (TOF) repair may
      influence LV stiffness. We hypothesized that LV stiffness is altered after TOF
      repair and related to myocardial calibrated integrated backscatter (cIB) and LV
      diastolic myocardial deformation. Seventy-seven TOF patients and 80 controls were
      studied. LV stiffness was assessed by diastolic wall strain (DWS) as defined by
      (LVPWsystole-LVPWdiastole)/LVPWsystole, where LVPW is LV posterior wall
      thickness, and stiffness index as defined by (E/e/LV end-diastolic dimension),
      where E and e are respectively early diastolic transmitral inflow and mitral
      annular velocities. Septal and LVPW cIB and LV diastolic strain rates were
      determined. Patients had significantly lower DWS (p < 0.001), higher stiffness
      index (p < 0.001), and greater cIB (p < 0.001). LV DWS correlated negatively with
      LV stiffness index (r = -0.31, p < 0.001), septal cIB (r = -0.21, p = 0.01), E/e
      ratio (r = -0.30, p < 0.001) and RV end-diastolic area (r = -0.31, p < 0.001),
      and positively with LV early (r = 0.33, p < 0.001) and late (r = 0.20, p = 0.01)
      diastolic strain rates and RV fractional area change (FAC) (r = 0.24, p = 0.003).
      Multivariate analysis revealed E/e (beta = -0.26, p = 0.008), RV end-diastolic
      area (beta = -0.20, p = 0.02), and RV FAC (beta = 0.18, p = 0.01) as significant
      correlates of DWS. Left ventricular stiffening occurs after TOF repair and is
      related to impaired LV diastolic myocardial deformation, myocardial cIB, and RV
      volume overload.

PMID- 28455533
TI  - First-principles design of nanostructured hybrid photovoltaics based on layered
      transition metal phosphates.
AB  - The performance of bulk organic and hybrid organic-inorganic heterojunction
      photovoltaics is often limited by high carrier recombination arising from
      strongly bound excitons and low carrier mobility. Structuring materials to
      minimize the length scales required for exciton separation and carrier collection
      is therefore a promising approach for improving efficiency. In this work, first
      principles computations are employed to design and characterize a new class of
      photovoltaic materials composed of layered transition metal phosphates (TMPs)
      covalently bound to organic absorber molecules to form nanostructured
      superlattices. Using a combination of transition metal substitution and organic
      functionalization, the electronic structure of these materials is systematically
      tuned to design a new hybrid photovoltaic material predicted to exhibit very low
      recombination due to the presence of a local electric field and spatially
      isolated, high mobility, two-dimensional electron and hole conducting channels.
      Furthermore, this material is predicted to have a large open-circuit voltage of
      1.7 V. This work suggests that hybrid TMPs constitute an interesting class of
      materials for further investigation in the search for achieving high efficiency,
      high power, and low cost photo Zirconium phosphate was chosen, in part, due to
      previous experiment voltaics.

PMID- 28455535
TI  - One-Step Fabrication of pH-Responsive Membranes and Microcapsules through
      Interfacial H-Bond Polymer Complexation.
AB  - Biocompatible microencapsulation is of widespread interest for the targeted
      delivery of active species in fields such as pharmaceuticals, cosmetics and agro
      chemistry. Capsules obtained by the self-assembly of polymers at interfaces
      enable the combination of responsiveness to stimuli, biocompatibility and scaled
      up production. Here, we present a one-step method to produce in situ membranes at
      oil-water interfaces, based on the hydrogen bond complexation of polymers between
      H-bond acceptor and donor in the oil and aqueous phases, respectively. This
      robust process is realized through different methods, to obtain capsules of
      various sizes, from the micrometer scale using microfluidics or rotor-stator
      emulsification up to the centimeter scale using drop dripping. The polymer layer
      exhibits unique self-healing and pH-responsive properties. The membrane is
      viscoelastic at pH = 3, softens as pH is progressively raised, and eventually
      dissolves above pH = 6 to release the oil phase. This one-step method of
      preparation paves the way to the production of large quantities of functional
      capsules.

PMID- 28455534
TI  - Xanthine oxidase inhibition by febuxostat attenuates stress-induced
      hyperuricemia, glucose dysmetabolism, and prothrombotic state in mice.
AB  - Chronic stress is closely linked to the metabolic syndrome, diabetes,
      hyperuricemia and thromboembolism, but the mechanisms remain elusive. We reported
      recently that stress targets visceral adipose tissue (VAT), inducing lipolysis,
      low-grade inflammation with production of inflammatory adipokines, metabolic
      derangements such as insulin resistance, and prothrombotic state. In the present
      study, we hypothesized the involvement of VAT xanthine oxidoreductase (XOR), a
      source of reactive oxygen species (ROS) and uric acid (UA) in the above
      processes. Restraint stress in mice resulted in upregulation of XOR and xanthine
      oxidase activity, accumulation of ROS in VAT as well as liver and intestine,
      increase in serum UA levels, upregulation of NADPH oxidase subunits and
      downregulation of antioxidant enzymes. Immunohistochemistry and RT-PCR analysis
      also showed that restraint stress induced VAT monocyte accumulation and
      proinflammatory adipokine production, resulting in reduced insulin sensitivity
      and induction of plasminogen activator inhibitor-1 and tissue factor in VAT.
      Treatment with febuxostat, a potent XO inhibitor, suppressed stress-induced ROS
      production and VAT inflammation, resulting in improvement of serum UA levels,
      insulin sensitivity, and prothrombotic tendency. Our results suggest that stress
      perturbs glucose and UA metabolism, and promotes prothrombotic status, and that
      XO inhibition by febuxostat might be a potential therapy for stress-related
      disorders.

PMID- 28455536
TI  - Cation and voltage dependence of lidocaine inhibition of the hyperpolarization
      activated cyclic nucleotide-gated HCN1 channel.
AB  - Lidocaine is known to inhibit the hyperpolarization-activated mixed cation
      current (Ih) in cardiac myocytes and neurons, as well in cells transfected with
      cloned Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels.
      However, the molecular mechanism of Ih inhibition by this drug has been limitedly
      explored. Here, we show that inhibition of Ih by lidocaine, recorded from Chinese
      hamster ovary (CHO) cells expressing the HCN1 channel, reached a steady state
      within one minute and was reversible. Lidocaine inhibition of Ih was greater at
      less negative voltages and smaller current amplitudes whereas the voltage
      dependence of Ih activation was unchanged. Lidocaine inhibition of Ih measured at
      -130 mV (a voltage at which Ih is fully activated) was reduced, and Ih amplitude
      was increased, when the concentration of extracellular potassium was raised to 60
      mM from 5.4 mM. By contrast, neither Ih inhibition by the drug nor Ih amplitude
      at +30 mV (following a test voltage-pulse to -130 mV) were affected by this rise
      in extracellular potassium. Together, these data indicate that lidocaine
      inhibition of Ih involves a mechanism which is antagonized by hyperpolarizing
      voltages and current flow.

PMID- 28455537
TI  - Interfacial chemical bonding-mediated ionic resistive switching.
AB  - In this paper, we present a unique resistive switching (RS) mechanism study of
      Pt/TiO2/Pt cell, one of the most widely studied RS system, by focusing on the
      role of interfacial bonding at the active TiO2-Pt interface, as opposed to a
      physico-chemical change within the RS film. This study was enabled by the use of
      a non-conventional scanning probe-based setup. The nanoscale cell is formed by
      bringing a Pt/TiO2-coated atomic force microscope tip into contact with a flat
      substrate coated with Pt. The study reveals that electrical resistance and
      interfacial bonding status are highly coupled together. An oxygen-mediated
      chemical bonding at the active interface between TiO2 and Pt is a necessary
      condition for a non-polar low-resistance state, and a reset switching process
      disconnects the chemical bonding. Bipolar switching mode did not involve the
      chemical bonding. The nature of chemical bonding at the TiO2-metal interface is
      further studied by density functional theory calculations.

PMID- 28455538
TI  - [APHAB scores for individual assessment of the benefit of hearing aid fitting].
AB  - OBJECTIVE: The Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire
      measures subjective hearing impairment on four different subscales pertaining to
      different listening situations. Using a very large patient cohort, this study
      aims to show how answers are distributed within the four subscales before and
      after hearing aid fitting, and what benefit the patients experience. The results
      are discussed on the basis of the available literature. PATIENTS AND METHODS:
      Between April 2013 and March 2016, 35,000 APHAB questionnaires from nine German
      statutory health insurance providers were evaluated. The average values before
      and after hearing aid fitting, as well as the benefit, were determined for all
      four APHAB subscales and analyzed graphically. RESULTS: The results of the
      subjective evaluation of hearing impairment before and after hearing aid fitting
      and the resultant benefit were plotted by percentile distribution graphs and
      boxplots. The data were analyzed statistically. There was no overlap of the
      interquartile ranges before and after hearing aid fitting in any of the APHAB
      subscales. In three scales (EC, BN and RV), the median improvement after hearing
      aid fitting was nearly 30 percentage points. In the AV subscale, this value was
      slightly negative. DISCUSSION: The percentile distribution graphs used in this
      study allow individual evaluation of subjective hearing impairment before and
      after hearing aid fitting, as well as of the resultant benefit, on the background
      of a huge database. Additionally, it is demonstrated why presentation as boxplots
      and the average benefit values calculated from these is problematic.

PMID- 28455539
TI  - Morphological and topographical anatomy of nutrient foramens in human metacarpals
      and their surgical importance.
AB  - PURPOSE: Trauma to the hand is extremely common, often resulting in metacarpal
      fractures and dislocations. The surgical intervention may be required for
      restoration of function and appearance. The preoperative, topographical knowledge
      of the nutrient foramens is valuable in such operative procedures to preserve the
      circulation for healing and good postoperative results. METHODS: The topographic
      and morphometric analysis of 250 non-pathological metacarpals (fifty each from
      first to fifth) was performed and the foraminal index of each metacarpal was
      evaluated. RESULTS: All the metacarpals were having single nutrient foramen
      except the second metacarpal which showed double nutrient foramens in two cases.
      The nutrient foramen was situated on the medial surface of first and second
      metacarpals and on lateral surface in third, fourth and fifth metacarpals in
      majority of the cases; however, their presence on anterior border (2.8%) was also
      noticed. The direction of the foramen was always away from the growing end. In
      88, 98.1, 90, 94 and 100% of first to fifth consecutive metacarpals, foraminal
      index ranged between 33.3 and 66.6, indicating their presence on middle third of
      the shaft. CONCLUSIONS: Though the majority (94%) of foramens were present on the
      middle third of the shaft, their presence on the proximal (2.8%) and distal third
      (3.2%) of the shaft cannot be ruled out. The presence of nutrient foramens on the
      anterior border of third metacarpal has not been classically reported. This
      information may be important for radiologists to avoid misdiagnosing them as
      pathology.

PMID- 28455540
TI  - A prospective study of corpus callosum regional volumes and neurocognitive
      outcomes following cranial radiation for pediatric brain tumors.
AB  - PURPOSE/OBJECTIVE(S): Cranial radiation therapy (CRT) may disrupt the corpus
      callosum (CC), which plays an important role in basic motor and cognitive
      functions. The aim of this prospective longitudinal study was to assess changes
      in CC mid-sagittal areas, CC volumes, and performance on neuropsychological (NP)
      tests related to the CC in children following CRT. MATERIALS/METHODS: Twelve
      pediatric patients were treated with CRT for primary brain malignancies. Thirteen
      age-matched healthy volunteers served as controls. Brain MRIs and NP assessment
      emphasizing motor dexterity, processing speed, visuomotor integration, and
      working memory (visual and verbal) were performed at baseline and at 6, 15, and
      27 months following completion of CRT. Linear mixed effects (LME) analyses were
      used to evaluate patient NP performance and changes in regional CC volumes (genu,
      anterior body, mid-body, posterior body, and splenium) and mid-sagittal areas
      over time and with radiation doses, correcting for age at CRT start. RESULTS: The
      mean age at CRT was 9.41 (range 1.2-15.7) years. The median prescription dose was
      54 (range 18-59.4) Gy. LME analysis revealed a significant decrease in overall CC
      volumes over time (p < 0.00001), with no overall effect of radiation dose.
      Analysis of individual CC regions demonstrated a significant decrease in all
      regional volumes over time (p < 0.00001) in patients, with no effect of radiation
      dose. Only in the splenium was there a trend toward a dose-dependent effect (p =
      0.093). Patients had significantly reduced NP performance across visits-most
      notably in motor dexterity and visual working memory (both p < 0.0001).
      CONCLUSIONS: These prospective data demonstrate a significant decrease in CC
      regional volumes after CRT, with associated decline in neurocognitive function,
      most notably in manual dexterity, attention, and working memory. Further
      prospective study of larger cohorts of patients is needed to establish the
      relationship between CRT dose, neuroanatomical, and functional changes in the CC.

PMID- 28455541
TI  - Review of management and morbidity of pediatric craniopharyngioma patients in a
      low-middle-income country: a 12-year experience.
AB  - BACKGROUND: Management of craniopharyngioma in children is challenging, and their
      quality of life can be significantly affected. Series describing this from low
      middle income countries (LMIC) are few. PATIENTS AND METHODS: The study provides
      a retrospective chart review of pediatric patients <18 years old, diagnosed with
      craniopharyngioma between 2003 and 2014, and treated at King Hussein Cancer
      Center, Jordan. RESULTS: Twenty-four patients (12 males) were identified. Median
      age at diagnosis was 7.4 years (0.9-16.4 years). Commonest symptoms were visual
      impairment and headache (71%). Review of seventeen preoperative MRIs showed
      hypothalamic involvement in 88% and hydrocephalus in 76%. Thirteen patients (54%)
      had multiple surgical interventions. Five patients (21%) had initial gross total
      resection. Eleven patients (46%) received radiotherapy and six (25%) intra-cystic
      interferon. Five years' survival was 87 +/- 7% with a median follow-up of 4.5
      years (0.3-12.3 years). Four patients (17%) died; one after post-operative
      cerebral infarction and three secondary to hypothalamic damage. At their last
      evaluation, all but one patient required multiple hormonal supplements. Ten
      patients (42%) had best eye visual acuity (VA) >20/40, and four (16%) were
      legally blind. Eleven patients (46%) were overweight/obese; one had gastric
      bypass surgery. Seven patients had hyperlipidemia, and eight developed fatty
      liver infiltration. Eleven patients (65%) were attending schools and one at
      college. Nine of the living patients (53%) expressed difficulty to engage in the
      community. CONCLUSIONS: Management of pediatric craniopharyngioma is particularly
      complex and demanding in LMIC. Multidisciplinary care is integral to optimize the
      care and minimize the morbidities. A management outline for LMIC is proposed.

PMID- 28455542
TI  - Antibacterial activities of sulfamethoxazolyl-azo-phenols and their Cu(II)
      complexes along with molecular docking properties.
AB  - Sulfamethoxazolyl-azo-phenols [SMX-N=N-C6H2(R)(R/)-OH] (1a, 2a) and their Cu(II)
      complexes, [Cu(SMX-N=N-C6H2(R)(R/)-O)2] (1b, 2b) (R = p-OMe, R/ = H, 1a/1b; R = p
      Cl, R/ = m-CH3, 2a/2b) show antibacterial sensitivity against Gram-positive
      bacteria, B. subtillis; IC50: 281.47 +/- 1.84 MUM (1a), 126.39 +/- 1.66 MUM (1b),
      and 279.94 +/- 3.15 MUM (2a), 123.62 +/- 1.27 MUM(2b), and Gram-negative
      bacteria, E. coli; IC50: 204.66 +/- 3.31 MUM (1a) and 89.05 +/- 1.48 MUM (1b),
      223.13 +/- 2.71 MUM (2a), and 98.26 +/- 1.59 MUM (2b). Interaction of DNA with
      free ligand (1a and 2a) is insignificant, while the complexes (1b and 2b)
      interact strongly and the binding constants are K b, 8.413 * 104 M-1 (1b) and
      6.56 * 105 M-1 (2b). Optimized structures of the compounds are docked with
      protein structure of DHPS (E. coli) to propose the most favoured binding mode of
      the drugs in the active site. The in silico test of the compound helps to
      understand drug metabolism, drug-protein interactions, and toxicity (ADMET).

PMID- 28455543
TI  - [Early atrophy of the conjunctiva after trabeculectomy with mitomycin C and
      collagen matrix implant].
AB  - Complete atrophy of the filtration bleb is a very rare complication after
      trabeculectomy with mitomycin C and collagen matrix implant (Ologen(r), Aeon
      Astron Corporation, Taipei, Taiwan). Clinically, the atrophy can present similar
      to blebitis. We report the case of a 71-year-old woman, in whom we resected the
      atrophic conjunctiva and reconstructed a filtration bleb using an amniotic
      membrane.

PMID- 28455544
TI  - Response to letter of the editor.

PMID- 28455545
TI  - Reliability and validity of the Pittsburgh Sleep Quality Index in breast cancer
      patients.
AB  - PURPOSE: We aimed to assess the factor structure, internal consistency, test
      retest reliability, and construct validity of the European Portuguese version of
      the Pittsburgh Sleep Quality Index (PSQI) in breast cancer patients. METHODS:
      This study was based on a cohort of breast cancer patients, among whom the PSQI
      was used to measure sleep quality three years after cancer diagnosis (N = 474). A
      sample of 62 participants underwent additional PSQI testing, wore a wrist
      actigraph for five consecutive days, and was reevaluated with the PSQI after one
      month. A confirmatory factor analysis, considering the components suggested by
      the principal component analysis (PCA), was performed to determine model fit. To
      evaluate internal consistency and test-retest reliability, Cronbach's alpha and
      intraclass correlation coefficient (ICC) were calculated, respectively. To assess
      construct validity, Spearman's correlation coefficients were computed between
      PSQI scores and actigraphy measures and other theoretical related constructs.
      RESULTS: PCA suggested one or two components. The latter showed better fit to the
      data, though the two factors were strongly correlated (r = 0.76) and internal
      consistency was not satisfactory for one of the factors. Regarding the one-factor
      model, internal consistency (Cronbach's alpha = 0.70) and test-retest reliability
      (ICC = 0.76) were adequate. Sleep duration, habitual sleep efficiency, and sleep
      disturbance dimensions were significantly correlated with the corresponding
      actigraphy measures; the PSQI global score derived from the one-factor model was
      more strongly correlated with subjective sleep complaints (r >= 0.60).
      CONCLUSIONS: The unidimensional construct of the European Portuguese version of
      the PSQI showed adequate reliability and validity among breast cancer patients.

PMID- 28455546
TI  - Safety of BTZ retreatment for patients with low-grade peripheral neuropathy
      during the initial treatment.
AB  - OBJECTIVE: Neuropathy is an important complication that may limit treatment
      options for patients with multiple myeloma. Previous studies have focused on
      treatment efficacy and have shown that retreatment with bortezomib (BTZ) is an
      effective treatment option. The goal of this study was to focus on the clinical
      manifestations of peripheral neuropathy (PN) and to retrospectively compare the
      incidence and severity of PN between the initial BTZ regimen and upon
      retreatment. Furthermore, this study evaluated how certain factors affect BIPN,
      which will help determine what conditions should be considered prior to
      retreatment. METHODS: Charts were reviewed from 93 patients who were retreated
      with a BTZ-containing regimen after previously being treated with this drug.
      RESULTS: Among the patients who developed PN, most patients in the study had low
      grade neuropathy during the initial BTZ treatment (n = 52, 68%). The results
      showed no evidence of cumulative toxicity, and there was no significant
      difference in the incidence and severity of PN upon retreatment. Factors such as
      the presence of baseline PN, number of prior treatments, dose of BTZ, and
      comorbidities did not increase the severity of PN upon retreatment. The lapse of
      time between the two regimens also did not affect the severity of PN. CONCLUSION:
      The results suggest that retreatment with BTZ may be a feasible option, without
      additional risks of PN, for MM patients even with peripheral neuropathy during
      their initial treatment with this drug.

PMID- 28455547
TI  - Associations of sleep disturbance with physical function and cognition in older
      adults with cancer.
AB  - PURPOSE: Although sleep disturbances are common in older adults, studies
      evaluating the prevalence of sleep disturbance and its influence on functional
      outcomes in older adults with cancer are few. In this study, we examined the
      prevalence of sleep disturbance and its association with physical function and
      cognition in older adults with cancer. METHODS: This is a cross-sectional study
      of patients who were referred and evaluated in the Specialized Oncology Care &
      Research in the Elderly (SOCARE) clinics at the Universities of Rochester and
      Chicago from May 2011 to October 2015. All patients underwent a geriatric
      assessment (GA) as part of their routine evaluation. Our final study cohort
      included patients who completed a sleep assessment and consented to the study. We
      collected demographics (age, sex, race, marital status, and education level) and
      clinical characteristics (depression, comorbidity, cancer type, and stage) from
      the GA and medical chart reviews. Presence of sleep disturbance was self-reported
      (yes/no). Physical function was assessed using Instrumental Activities of Daily
      Living (IADLs), physical activity (PA) survey, falls in the preceding 6 months,
      and Short Physical Performance Battery (SPPB). Cognition was screened using the
      Blessed Orientation-Memory-Concentration Test (impairment >4) or Montreal
      Cognitive Assessment (impairment <26). Bivariate and multivariable analyses were
      used to examine the associations between sleep disturbance with functional
      outcomes and cognition. RESULTS: We included 389 older patients. The prevalence
      of sleep disturbance was 40%. Sixty-eight percent had >=1 IADL impairment, 76%
      had PA limitation, 37% had >=1 fall, 70% had impairment on SPPB, and 47% screened
      positive for cognitive impairment. On bivariate analyses, sleep disturbance was
      associated with IADL impairment (odds ratio [OR] 1.96, 95% confidence interval
      [CI] 1.23-3.13, P = 0.005), and PA limitation (OR 2.43, 95% CI 1.38-4.28, P =
      0.002). The associations remained significant on multivariable analyses. Sleep
      disturbance was not significantly associated with falls, impairment on SPPB, and
      performance on the cognitive screen. CONCLUSION: Sleep disturbance was associated
      with IADL impairment and PA limitation. It is important for oncologists to
      inquire about sleep problems, and these patients should also be screened for
      functional impairment if sleep disturbance was present.

PMID- 28455548
TI  - Feasibility of objectively measured physical activity and sedentary behavior in
      patients with malignant pleural effusion.
AB  - PURPOSE: Malignant pleural effusion (MPE) affects 1 million people worldwide
      annually and can significantly impair physical activity. Accelerometry is a
      validated method of objectively assessing physical activity. The purpose of this
      study was to determine the compliance in patients with MPE to accelerometry and
      describe their activity. METHODS: Patients with MPE wore an Actigraph GT3X
      accelerometer over a 7-day continuous wear protocol. Compliance was measured as
      the percent of patients who had >=4 valid days (i.e., 8-h/day of waking wear
      time). Eastern Cooperative Oncology Group performance status was documented the
      day of actigraphy initialization. RESULTS: Forty-six patients with MPE received
      accelerometers; 44 (95.7%) returned their device. No complications were reported
      on their use. Forty subjects (90.9%) had >=4 valid days of wear-time. Patients
      spent most of their waking hours sedentary [mean 11.0 h (SD 1.95)], with limited
      participation in moderate and vigorous physical activity [mean 9.5 min (SD
      14.16)]. Compared to patients with better performance status (n = 32), patients
      with poorer performance status (n = 11) spent significantly more hours/day
      sedentary [mean difference 2.1 (CI 0.86-3.32); p = 0.001], as did those who
      survived <3 months (n = 5) compared to >12 months (n = 27) [mean difference 2.6
      (CI 0.49-4.77); p = 0.013). CONCLUSION: Accelerometry was applied successfully in
      patients with MPE with high compliance and no adverse events. This is the first
      reported objectively measured physical activity in patients with MPE and revealed
      high sedentary behavior and low physical activity. The data reflected patient
      performance status and discriminated between survival groups. Accelerometry can
      provide a useful measure for future interventional studies in patients with MPE.

PMID- 28455549
TI  - Involution processes of follicular atresia and post-ovulatory complex in a
      characid fish ovary: a study of apoptosis and autophagy pathways.
AB  - Recent studies seem to indicate that apoptosis and autophagy can act
      cooperatively in fish ovaries in order to achieve more effective ovarian
      regression after spawning. Considering the importance of tissue remodeling in
      ovarian functioning, we sought to morphologically characterize the involution
      processes of follicular atresia and post-ovulatory complexes using Astyanax
      altiparanae as an experimental model, and to determine the location of proteins
      involved in apoptosis and autophagy throughout this process. Fifteen females were
      collected after reproductive management. Fragments of the left ovaries were
      removed, fixed, and prepared for light microscopy and immunofluorescence
      analyses. The main characteristics of the involution processes were found to be
      consistent with previous descriptions. However, there were certain morphological
      peculiarities that do not appear to have been described for any other species
      thus far. These peculiarities may be related to the focus of this study on a
      single species, which allows for a more detailed investigation into morphological
      changes than studies on multiple species. Autophagy was also found to precede
      apoptosis in both involution processes in A. altiparanae. This may be related to
      the energy recycling process required before the removal of degenerated
      follicular cells by apoptosis. Thus, these results support the idea that there is
      crosstalk between autophagy and apoptosis pathways in ovarian involution
      processes, as well as the idea that the cell death pathways of these processes
      are conserved between teleost species with external fertilization.

PMID- 28455550
TI  - Contribution of native phosphorous-solubilizing bacteria of acid soils on
      phosphorous acquisition in peanut (Arachis hypogaea L.).
AB  - The present investigation analyzes the in vitro P solubilization [Ca-P, Al-P,
      Fe(II)-P, and Fe(III)-P] efficiency of native PSB strains from acid soils of
      Odisha and exploitation of the same through biofertilization in peanut (Arachis
      hypogaea L.) growth and P acquisition. One hundred six numbers of soil samples
      with pH <= 5.50 were collected from five districts of Odisha viz., Balasore,
      Cuttack, Khordha, Keonjhar, and Mayurbhanj. One bacterial isolate from each
      district were selected and analyzed for their P solubilization efficiency in
      National Botanical Research Institute Phosphate broths with Ca, Al, and Fe
      complexed phosphates. CTC12 and KHD08 transformed more amount of soluble P from
      Ca-P (CTC12 393.30 mg/L; KHD08 465.25 mg/L), Al-P (CTC12 40.00 mg/L; KHD08 34.50
      mg/L), Fe(III)-P (CTC12 175.50 mg/L; KHD08 168.75 mg/L), and Fe(II)-P (CTC12
      47.40 mg/L; KHD08 42.00 mg/L) after 8 days of incubation. The bioconversion of P
      by all the five strains in the broth medium followed the order Ca-P > Fe(III)-P >
      Fe(II)-P > Al-P. The identified five strains were Bacillus cereus BLS18
      (KT582541), Bacillus amyloliquefaciens CTC12 (KT633845), Burkholderia cepacia
      KHD08 (KT717633), B. cepacia KJR03 (KT717634), and B. cepacia K1 (KM030037) and
      further studied for biofertilization effects on peanut. CTC12 and KHD08 enhanced
      the soil available P around 65 and 58% and reduced the amount of each Al3+ about
      79 and 81%, respectively, over the uninoculated control pots in the peanut
      rhizosphere. Moreover, all tested PSB strains could be able to successfully
      mobilize P from inorganic P fractions (non-occluded Al-P and Fe-P). The strains
      CTC12 and KHD08 increased the pod yield (114 and 113%), shoot P (92 and 94%), and
      kernel P (100 and 101%), respectively, over the control. However, B.
      amyloliquefaciens CTC12 and B. cepacia KHD08 proved to be the potent P
      solubilizers in promoting peanut growth and yield.

PMID- 28455551
TI  - Erratum to: Older age at the completion of linear growth is associated with an
      increased risk of adult glioma.

PMID- 28455552
TI  - Two new antimalarial quassinoid derivatives from the stems of Brucea javanica.
AB  - Phytochemical investigation of the stems from Brucea javanica led to the
      isolation of two new quassinoids, brujavanol C (1) and brujavanol D (2), together
      with six known compounds (3-8). The chemical structures were elucidated by means
      of various spectroscopic methods. All the isolated compounds were evaluated for
      antimalarial activity against Plasmodium falciparum and compounds 6 and 7
      exhibited the most potent activity against the K1 strain, with IC50 values of
      1.41 and 1.06 MUM, respectively.

PMID- 28455553
TI  - New ellagitannins from Tiencha and their inhibitory activity against dental
      plaque.
AB  - Four new galloyl-oxygen-diphenyl (GOD)-type ellagitannins, brambliins A-D (1-4),
      were isolated from the leaves of Rubus suavissimus. Their structures were
      elucidated by extensive spectroscopic analyses and the absolute configurations of
      1-4 were determined by chemical and phytochemical evidence. These GOD-type
      ellagitannins inhibited the formation of dental plaque, which is beneficial for
      oral hygiene.

PMID- 28455554
TI  - Placing negative multi-gene panel results into clinical context.

PMID- 28455555
TI  - Improved Sleep, Diet, and Exercise in Adults with Serious Mental Illness: Results
      from a Pilot Self-Management Intervention.
AB  - Compared to the general population, adults with serious mental illnesses have
      elevated rates of medical morbidity resulting in a reduced life expectancy of
      approximately 15 years. Chronic disease self-management programs for adults with
      serious mental and chronic medical illnesses show some promise in improving
      physical health-related outcomes, yet none of them address sleep quality. Poor
      sleep affects a majority of adults with serious mental illness and is robust risk
      factor for physical morbidity and premature mortality. This pilot project
      examined the impact of a 14-week educational and support group that included
      sleep quality as a cornerstone in promoting wellness and self-management in 78
      adults with serious mental illness and poor health. Results provide preliminary
      data that the self-management program was associated with significant
      improvements in self-reported sleep quality at post-intervention. At 3-month
      follow-up, participants reported additional increases in sleep quality as well as
      in healthy diet and exercise frequency. Addressing sleep quality as part of self
      management and wellness programs may be a viable approach to assist adults with
      chronic mental and physical illnesses to adopt health-promoting changes.

PMID- 28455556
TI  - Fusarium diseases of maize associated with mycotoxin contamination of
      agricultural products intended to be used for food and feed.
AB  - Infections of maize with phytopathogenic and toxinogenic Fusarium spp. may occur
      throughout the cultivation period. This can cause different types of diseases in
      vegetative and generative organs of the plant. Along with these infections,
      mycotoxins are often produced and accumulated in affected tissues, which could
      pose a significant risk on human and animal health when entering the food and
      feed chain. Most important fungal species infecting European maize belong to the
      Fusarium sections Discolour and Liseola, the first being more prevalent in cooler
      and humid climate regions than the second predominating in warmer and dryer
      areas. Coexistence of several Fusarium spp. pathogens in growing maize under
      field conditions is the usual case and may lead to multi-contamination with
      mycotoxins like trichothecenes, zearalenone and fumonisins. The pathways how the
      fungi gain access to the target organs of the plant are extensively described in
      relation to specific symptoms of typical rot diseases regarding ears, kernels,
      rudimentary ears, roots, stem, leaves, seed and seedlings. Both Gibberella and
      Fusarium ear rots are of major importance in affecting the toxinogenic quality of
      grain or ear-based products as well as forage maize used for human or animal
      nutrition. Although rudimentary ears may contain high amounts of Fusarium toxins,
      the contribution to the contamination of forage maize is minor due to their small
      proportion on the whole plant dry matter yield. The impact of foliar diseases on
      forage maize contamination is regarded to be low, as Fusarium infections are
      restricted to some parts on the leaf sheaths and husks. Mycotoxins produced in
      rotted basal part of the stem may contribute to forage maize contamination, but
      usually remain in the stubbles after harvest. As the probability of a more severe
      disease progression is increasing with a prolonged cultivation period, maize
      should be harvested at the appropriate maturity stage to keep Fusarium toxin
      contamination as low as possible. Ongoing surveillance and research is needed to
      recognise changes in the spectrum of dominating Fusarium pathogens involved in
      mycotoxin contamination of maize to ensure safety in the food and feed chain.

PMID- 28455559
TI  - Prevalence of rheumatoid arthritis in the United States adult population in
      healthcare claims databases, 2004-2014.
AB  - This study aimed to determine the prevalence of rheumatoid arthritis in the
      United States (US) adult insured population from 2004 to 2014. This was an
      observational, retrospective, cross-sectional study based on US administrative
      health insurance claims databases (Truven Health MarketScan(r) Research database
      and IMS PharMetrics Plus database). Trends in RA prevalence focusing on the 10
      year period covering January 1, 2004-December 31, 2014 were analyzed using a
      validated algorithm for the identification of RA. Prevalence rates in the
      databases were determined and age- and gender-adjusted rates were projected to
      the US population in 2014. Analysis of data from the two databases indicated that
      the RA prevalence rate in commercially insured adult US population ranged from
      0.41 to 0.54% from 2004 to 2014. The prevalence varied substantially by gender
      and age in each year and increased gradually across the years for most subgroups.
      In 2014, out of 31,316,902 adult patients with continuous enrollment in the
      Truven Health MarketScan(r) Research database, 157,634 (0.50%) patients met our
      criteria for RA. Similarly, out of 35,083,356 adult patients in the IMS
      PharMetrics Plus database, 139,300 (0.50%) patients met our criteria for RA. In
      2014, the overall age-adjusted prevalence of RA ranged from 0.53 to 0.55% (0.29
      0.31% for males and 0.73-0.78% for females). The prevalence of RA in the US
      appeared to increase during the period from 2004 to 2014, affecting a
      conservative estimate of 1.28-1.36 million adults in 2014.

PMID- 28455557
TI  - Three Cdk1 sites in the kinesin-5 Cin8 catalytic domain coordinate motor
      localization and activity during anaphase.
AB  - The bipolar kinesin-5 motors perform essential functions in mitotic spindle
      dynamics. We previously demonstrated that phosphorylation of at least one of the
      Cdk1 sites in the catalytic domain of the Saccharomyces cerevisiae kinesin-5 Cin8
      (S277, T285, S493) regulates its localization to the anaphase spindle. The
      contribution of these three sites to phospho-regulation of Cin8, as well as the
      timing of such contributions, remains unknown. Here, we examined the function and
      spindle localization of phospho-deficient (serine/threonine to alanine) and
      phospho-mimic (serine/threonine to aspartic acid) Cin8 mutants. In vitro, the
      three Cdk1 sites undergo phosphorylation by Clb2-Cdk1. In cells, phosphorylation
      of Cin8 affects two aspects of its localization to the anaphase spindle,
      translocation from the spindle-pole bodies (SPBs) region to spindle microtubules
      (MTs) and the midzone, and detachment from the mitotic spindle. We found that
      phosphorylation of S277 is essential for the translocation of Cin8 from SPBs to
      spindle MTs and the subsequent detachment from the spindle. Phosphorylation of
      T285 mainly affects the detachment of Cin8 from spindle MTs during anaphase,
      while phosphorylation at S493 affects both the translocation of Cin8 from SPBs to
      the spindle and detachment from the spindle. Only S493 phosphorylation affected
      the anaphase spindle elongation rate. We conclude that each phosphorylation site
      plays a unique role in regulating Cin8 functions and postulate a model in which
      the timing and extent of phosphorylation of the three sites orchestrates the
      anaphase function of Cin8.

PMID- 28455558
TI  - Enzyme-substrate relationships in the ubiquitin system: approaches for
      identifying substrates of ubiquitin ligases.
AB  - Protein ubiquitylation is an important post-translational modification,
      regulating aspects of virtually every biochemical pathway in eukaryotic cells.
      Hundreds of enzymes participate in the conjugation and deconjugation of
      ubiquitin, as well as the recognition, signaling functions, and degradation of
      ubiquitylated proteins. Regulation of ubiquitylation is most commonly at the
      level of recognition of substrates by E3 ubiquitin ligases. Characterization of
      the network of E3-substrate relationships is a major goal and challenge in the
      field, as this expected to yield fundamental biological insights and
      opportunities for drug development. There has been remarkable success in
      identifying substrates for some E3 ligases, in many instances using the standard
      protein-protein interaction techniques (e.g., two-hybrid screens and co
      immunoprecipitations paired with mass spectrometry). However, some E3s have
      remained refractory to characterization, while others have simply not yet been
      studied due to the sheer number and diversity of E3s. This review will discuss
      the range of tools and techniques that can be used for substrate profiling of E3
      ligases.

PMID- 28455560
TI  - Factors associated with adverse postoperative outcomes in patients with long bone
      post-traumatic osteomyelitis.
AB  - AIMS: To evaluate short-term clinical and functional outcomes following operative
      treatment of long bone post-traumatic osteomyelitis (PTOM). METHODS: We
      retrospectively analyzed a consecutive cohort of 142 adult patients undergoing
      operative treatment of long bone PTOM at our Level I trauma center over a 10-year
      study period. In addition to subjective patient evaluations, surveyed
      postoperative outcomes included incidence of residual infection, fracture
      malunion or nonunion, and requirement for limb amputation. All included patients
      had a minimum follow-up of 12 months postoperatively. RESULTS: Patients suffering
      an adverse postoperative outcome tended to have a higher incidence of
      polymicrobial infection (25.4 vs. 11.4%, p = 0.042) and requirement for skin
      grafting (58.1 vs. 37.9%, p = 0.024) and free-flap procedures (43.6 vs. 19.5%, p
      = 0.003) compared to those achieving complete healing. Sequential administration
      of parenteral and oral antibiotic therapies was associated with a reduced
      incidence of adverse postoperative outcome (p = 0.047). DISCUSSION: Patients with
      long bone PTOM and extensive soft tissue defects often fail to develop complete
      remission of their symptoms by 12 months postoperatively. Sequential
      administration of parenteral and oral antibiotics may help to limit infection
      recurrence. Further research is required to inform optimal treatment strategy.

PMID- 28455562
TI  - Erratum to: Bone Matrix Maturation in a Rat Model of Intra-Cortical Bone
      Remodeling.

PMID- 28455561
TI  - Radiographic assessment of distal femur cemented stems in tumor endoprostheses.
AB  - BACKGROUND: Distal femoral endoprosthesis (DFE) has become the optimal method of
      reconstruction in the skeletally mature patients treated for malignant bone
      tumor. Albeit literature has reported wide range of aseptic loosening in cemented
      components (6-32%), few authors showed that cement was not detrimental to long
      term success of primary distal femoral implants possibly relating to cementing
      technique. METHODS: A series of consecutive of DFE (MRS and GMRS, Styker
      Orthopaedics, Mahwah, NJ) was retrospectively reviewed for evidence of loosening
      on plain radiographs. All prostheses had the standard straight 127-mm stem and a
      cemented polyethylene tibial component. Cementing technique involved reaming line
      to line to the selected stem size and cementing without pressurization.
      Radiographs were assessed by two independent blinded reviewers and scored for
      radiolucent zones (>1 mm) and graded as not loose, possibly, probable and
      definite loose. Furthermore, the final reamer/stem diameters, length of
      resection, tumor type, adjuvant treatment modalities, bushing exchange/revision
      surgery and infection rate were recorded. RESULTS: There were 70 patients and
      none were lost to follow-up. The average radiographic follow-up was 7.2 years
      (58% had f/u >5 years). Examiner A found 89% of femoral components to be "Not
      Loose" and 11% (n = 6) "Possibly Loose". Examiner B found 96% of femoral
      components to be "Not Loose" and 4% (n = 2) to be "Possibly Loose". No components
      scored as probably or definitely loose. Two DFE stems were reported as "Possibly
      Loose" by both reviewers. No femoral stem required revisions for either
      loosening, femur fracture or metal failure. Although infection was frequent,
      there was no septic loosening. CONCLUSION: Despite our study limitations, no
      radiographic evidence of loosening was found. Cementing distal femur prosthesis
      with a tight canal fit and with a thin and inconsistent cement mantle appears to
      be a viable option at short and medium term.

PMID- 28455563
TI  - Feeling the Impact of Long-Term Total Parenteral Nutrition.

PMID- 28455564
TI  - Sorption of sulfathiazole in the soil treated with giant Miscanthus-derived
      biochar: effect of biochar pyrolysis temperature, soil pH, and aging period.
AB  - Agricultural soil was treated with biochar (5% w/w) produced from two pyrolysis
      temperatures (400 and 700  degrees C) of giant Miscanthus (GMC-400 and GMC-700,
      respectively), and the subsequent sorption of sulfathiazole (STZ) was evaluated
      as a function of pH (2, 5, and 7) and aging period (0, 3, and 6 months). Because
      sorption was nonlinear, with 0.51 < N < 0.75, the linearized sorption coefficient
      (K d*) was used for the comparison across samples. The K d* of GMC-400 treatment
      (3.96-9.96 L kg-1) was higher than that of GMC-700 treatment (1.27-3.38 L kg-1).
      In laps of aging period over 6 months, the sorption of GMC-400-treated soil had
      gradually increased to be 3.3 times higher than that of untreated soil, whereas
      there was no statistical difference for GMC-700 treatment. Results of FTIR and
      SEM analyses revealed that the number of O-containing functional groups in the
      GMC-400 treatment increases and the micropores of GMC-700 are deformed over time.
      Sorption was also pH-dependent in the order of pH 2 > pH 5 > pH 7. The sorption
      hysteresis (H) index for the GMC-400 treatment was higher at pH 7 (3.99) than at
      pH 5(2.53), and both values had increased after 6 months (4.18 and 3.17,
      respectively). The results of this study clearly demonstrate that the sorption of
      STZ on GMC-treated soils is greatly enhanced, mainly through the greater
      micropore surfaces, the abundance of hydrophilic functional groups over time, and
      pi+-pi electron donor-acceptor interaction at low pH.

PMID- 28455565
TI  - Validation of ozone response functions for annual Mediterranean pasture species
      using close-to-field-conditions experiments.
AB  - Ozone (O3) critical levels have been established under the Long-Range
      Transboundary Air Pollution Convention to assess the risk of O3 effects in
      European vegetation. A recent review study has led to the development of O3
      critical levels for annual Mediterranean pasture species using plants growing in
      well-watered pots at a coastal site and under low levels of competition. However,
      uncertainties remain in the extrapolation of the O3 sensitivity of these species
      under natural conditions. The response of two O3-sensitive annual Mediterranean
      pasture Trifolium species at the coastal site was compared with the response of
      the same species growing at a continental site, in natural soil and subject to
      water-stress and inter-specific competition, representing more closely their
      natural habitat. The slopes of exposure- and dose-response relationships derived
      for the two sites showed differences in the response to O3 between sites
      attributed to differences in environmental growing conditions, growing medium and
      the level of inter-specific competition, but the effect of the individual factors
      could not be assessed separately. Dose-based O3 indices partially explained
      differences due to environmental growing conditions between sites. The slopes
      showed that plants were more sensitive to O3 at the continental site, but
      homogeneity of slopes tests revealed that results from both experimental sites
      may be combined. Although more experimental data considering complex inter
      specific competition situations and the effect of important interactive factors
      such as nitrogen would be needed, these results confirm the validity of applying
      the current flux-based O3 critical level under close to natural growing
      conditions. The AOT40-based O3 critical level derived at the coastal site was
      also considered a suitable risk indicator in close to natural growing conditions
      in the absence of soil moisture limitations on plant growth.

PMID- 28455566
TI  - Toxicological effects of Sphaeranthus indicus Linn. (Asteraceae) leaf essential
      oil against human disease vectors, Culex quinquefasciatus Say and Aedes aegypti
      Linn., and impacts on a beneficial mosquito predator.
AB  - Use of environmentally friendly, decomposable natural products for effective
      vector control has gained considerable momentum in modern society. In this study,
      essential oil of Sphaeranthus indicus (Si-EO) was extracted and further
      phytochemical screening revealed fourteen compounds with prominent peak area
      percentage of 24.9 and 22.54% in 3,5-di-tert-butyl-4-hydroxybenzaldehyde and
      benzene,2-(1,1-dimethylethyl)-1,4-dimethoxy, respectively. The Si-EO was further
      evaluated for their larvicidal response against Culex quinquefasciatus and Aedes
      aegypti at different dosages (62.5, 125, 250 and 500 ppm). The Si-EO displayed
      prominent larvicidal activity at higher concentration (500 ppm) against both
      species of mosquitoes. The LC50 and LC90 values of oils were observed at 130 and
      350 ppm against C. quinquefasciatus larvae and at 140 and 350 ppm against A.
      aegypti larvae, respectively. Repellent bioassay established higher protection
      rate at 200 ppm up to 120 min against both the mosquitoes. However, adulticidal
      response displayed higher mortality rate only at 700 and 800 ppm against C.
      quinquefasciatus and A. aegypti, respectively. Toxicological screening against
      mosquito predator Toxorhynchites splendens revealed that the Si-EO was harmless
      even at the concentration of 1500 ppm. Overall, these results suggest that the Si
      EO plays a significant role as a new bio-rational product against ecological
      burden mosquito vectors which provides an eco-friendly alternative to synthetic
      pesticides.

PMID- 28455567
TI  - Effect of low-molecular-weight organic acids on hematite dissolution promoted by
      desferrioxamine B.
AB  - Siderophores, as strong chelators specific to iron, have been intensively studied
      in relation to the facilitation of biological iron acquisition from iron oxides.
      In this study, the dissolution of hematite in the presence of the siderophore
      desferrioxamine B (DFOB) and three low-molecular-weight organic acids (LMWOAs,
      i.e., oxalic, citric, or malic acid) was investigated at three pH conditions
      (3.0, 5.5, and 9.0). Hematite dissolution was pH-dependent and LMWOA-specific.
      The adsorption of DFOB on hematite was significantly higher at pH 9.0 than at the
      other pH values. The adsorption of oxalic acid on hematite, however, showed a
      descending trend as pH was increased, and adsorption of citric and malic acids
      was not significantly affected by pH. The Fourier transform infrared (FTIR)
      results also indicated the occurrence of these ligands' adsorption. After
      acidification, dissolved iron was detected only in suspensions of hematite pre
      adsorbed with oxalic acid at pH 5.5 and 9.0 or pre-adsorbed with citric acid at
      pH 5.5, indicating that these LMWOAs promoted the formation of labile iron on the
      hematite surface. Based on previous research and the results of this study, a
      hypothetical model is proposed. These results provide insight into the effect of
      LMWOAs on the dissolution of hematite promoted by DFOB.

PMID- 28455568
TI  - Chemical characteristics and source apportionment of PM2.5 using PCA/APCS, UNMIX,
      and PMF at an urban site of Delhi, India.
AB  - The present study investigated the comprehensive chemical composition [organic
      carbon (OC), elemental carbon (EC), water-soluble inorganic ionic components
      (WSICs), and major & trace elements] of particulate matter (PM2.5) and
      scrutinized their emission sources for urban region of Delhi. The 135 PM2.5
      samples were collected from January 2013 to December 2014 and analyzed for
      chemical constituents for source apportionment study. The average concentration
      of PM2.5 was recorded as 121.9 +/- 93.2 MUg m-3 (range 25.1-429.8 MUg m-3),
      whereas the total concentration of trace elements (Na, Ca, Mg, Al, S, Cl, K, Cr,
      Si, Ti, As, Br, Pb, Fe, Zn, and Mn) was accounted for ~17% of PM2.5. Strong
      seasonal variation was observed in PM2.5 mass concentration and its chemical
      composition with maxima during winter and minima during monsoon seasons. The
      chemical composition of the PM2.5 was reconstructed using IMPROVE equation, which
      was observed to be in good agreement with the gravimetric mass. Source
      apportionment of PM2.5 was carried out using the following three different
      receptor models: principal component analysis with absolute principal component
      scores (PCA/APCS), which identified five major sources; UNMIX which identified
      four major sources; and positive matrix factorization (PMF), which explored seven
      major sources. The applied models were able to identify the major sources
      contributing to the PM2.5 and re-confirmed that secondary aerosols (SAs),
      soil/road dust (SD), vehicular emissions (VEs), biomass burning (BB), fossil fuel
      combustion (FFC), and industrial emission (IE) were dominant contributors to
      PM2.5 in Delhi. The influences of local and regional sources were also explored
      using 5-day backward air mass trajectory analysis, cluster analysis, and
      potential source contribution function (PSCF). Cluster and PSCF results indicated
      that local as well as long-transported PM2.5 from the north-west India and
      Pakistan were mostly pertinent.

PMID- 28455569
TI  - Photolysis of pharmaceuticals and personal care products in the marine
      environment under simulated sunlight conditions: irradiation and identification.
AB  - The photochemical fate of 16 pharmaceuticals and personal care products (PPCPs)
      found in the environment has been studied under controlled laboratory conditions
      applying a sunlight simulator. Aqueous samples containing PPCPs at
      environmentally relevant concentrations were extracted by solid-phase extraction
      (SPE) after irradiation. The exposed extracts were subsequently analysed by
      liquid chromatography combined with triple quadrupole mass spectrometry (HPLC
      MS/MS) for studying the kinetics of photolytic transformations. Almost all
      exposed PPCPs appeared to react with a half-life time (tau 1/2) of less than 30
      min. For ranitidine, sulfamethoxazole, diclofenac, warfarin, sulfamethoxazole and
      ciprofloxacin, tau1/2 was found to be even less than 5 min. The structures of
      major photolysis products were determined using quadrupole-time-of-flight mass
      spectrometry (QToF) and spectroscopic data reported in the literature. For
      diclofenac, the transformation products carbazol-1-yl-acidic acid and 8-chloro-9H
      carbazol-1-yl-acetic acid were identified based on the mass/charge ratio of
      protonated ions and their fragmentation pattern in negative electrospray
      ionization (ESI--QTOF). Irradiation of carbamazepine resulted in three known
      products: acridine, carbamazepine-10,11-epoxide, and 10,11-dihydro-10,11
      dihydroxy-carbamazepine, whereas acetaminophen was photolytically transformed to
      1-(2-amino-5 hydroxyphenyl) ethenone. These photochemical products were
      subsequently identified in seawater or fish samples collected at sites exposed to
      wastewater effluents on the Saudi Arabian coast of the Red Sea.

PMID- 28455570
TI  - Fast atrazine degradation by the mixed cultures enriched from activated sludge
      and analysis of their microbial community succession.
AB  - In this study, fast atrazine degradation by the mixed bacterial cultures from
      sewage sludge was investigated. The acquired activated cultures showed great
      capability in atrazine degradation. The biodegradation process was well fitted
      into a pseudo-first reaction kinetic model. Atrazine could inhibit the
      propagation of ammonium oxidation bacteria and nitrite oxidation bacteria,
      decreasing the ammonium removal rate and the accumulation of nitrite. Only 162
      172 reads of Nitrosomonadaceae and no Nitrospirales were detected after atrazine
      was exposed to the mixed cultures. The bacterial community structures in the
      cultures under different inoculation conditions (with or without atrazine) were
      investigated to explore the mechanism of atrazine degradation. Our results show
      that the genera Thiobacillus and Ferruginibacter were the most possible
      candidates responsible for the degradation of atrazine.

PMID- 28455571
TI  - Urinary levels of phthalate metabolites and associations with demographic
      characteristics in Korean adults.
AB  - The objective of this study is to assess human exposure to phthalates and its
      associations with demographic characteristics of the subjects in the Korean
      National Human Biomonitoring Survey. The subjects aged between 18 and 69 were
      selected through nationwide stratified sampling. A total of 1874 urine samples
      were collected and stored at -20  degrees C until measurement for ten selected
      metabolites of phthalates (MnBP, MiBP, MBzP, MCHP, MnOP, MEHP, MEOHP, MEHHP,
      MiNP, and MiDP) using high-performance liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). The difference in the level of urinary phthalate
      metabolites by the characteristics of the subjects was tested for statistical
      significance using SAS Surveyreg procedure. The coefficients and standard errors
      from multiple linear regressions were exponentiated to estimate the adjusted
      proportional change (APC) and 95% CIs compared with a referent level. The
      proportion of data above LOQ was less than 20% for MCHP, MnOP, MiNP, and MiDP.
      Geometric means of creatinine-adjusted concentrations (unit: MUg/g creatinine) of
      six other phthalate metabolites among Korean adults were 41.7 (95% CI 39.6-43.9)
      for MnBP, 17.1 (95% CI 16.1-18.1) for MiBP, 15.7 (95% CI 14.4-17.1) for MBzP,
      8.65 (95% CI 8.10-9.22) for MEHP, 17.5 (95% CI 16.8-18.3) for MEOHP, and 38.1
      (95% CI 36.2-40.2) for MEHHP. Urinary level of phthalates tended to be higher
      among subjects with older age, females, and those with vigorous daily physical
      activity and tended to be lower among drinkers and those with higher income. Our
      results suggest that the level of phthalate exposure is significant among Korean
      adults and thus warrants further studies to identify major source and route of
      exposure to phthalates.

PMID- 28455572
TI  - Accumulation of heavy metals in soil-crop systems: a review for wheat and corn.
AB  - The health risks arising from heavy metal pollution (HMP) in agricultural soils
      have attracted global attention, and research on the accumulation of heavy metals
      in soil-plant systems is the basis for human health risk assessments. This review
      studied the accumulation of seven typical heavy metals-Cd, Cr, As, Pb, Hg, Cu,
      and Zn-in soil-corn and soil-wheat systems. The findings indicated that, in
      general, wheat was more likely to accumulate heavy metals than corn.
      Bioconcentration factor (BCF) of the seven heavy metals in wheat and corn grains
      decreased exponentially with their average concentrations in soil. The seven
      heavy metals were ranked as follows, in ascending order of accumulation in corn
      grains: Pb < Cr < Zn < As < Cu < Cd <Hg. As for the order of accumulation in
      wheat grains, their ranking was as follows: Zn < Pb < Cr < Cu < As < Hg <Cd. The
      minimum BCFs of Cd, Cr, As, Pb, Hg, Cu, and Zn in corn grains were 0.054, 6.65 *
      10-4, 7.94 * 10-4, 0.0044, 0.028, 0.13, and 0.19, respectively. The corresponding
      BCFs values for wheat grains were 0.25, 0.0045, 5.42 * 10-4, 0.009, 4.03 * 10-4,
      0.11, and 0.054, respectively.

PMID- 28455573
TI  - Filaggrin gene polymorphism associated with Epstein-Barr virus-associated tumors
      in China.
AB  - Mutations of filaggrin gene (FLG) have been identified as the cause of ichthyosis
      vulgaris, while recently FLG mutations were found to be associated with gastric
      cancer. This study aimed to investigate the association of filaggrin polymorphism
      with Epstein-Barr virus-associated tumors in China. A total of 200 patients with
      three types of tumors and 117 normal control samples were genotyped at three
      common FLG mutation loci (rs3126085, K4671X, R501X) by using Sequenom MassARRAY
      technique. The chi 2 test was used to evaluate the relationship between the
      mutation and the three kinds of tumors. A two-sided P value of <0.05 was
      considered statistically significant. The results showed that two single
      nucleotide polymorphism (SNP) loci (rs3126085, K4671X) were significantly
      associated with nasopharyngeal carcinoma in genetic model. In addition, the two
      SNPs K4671X and rs3126085 were related to Epstein-Barr virus (EBV)-associated
      gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC),
      respectively. Furthermore, allele distributions in EBVaGC and EBVnGC were
      verified to be different in both SNP loci.

PMID- 28455574
TI  - Action steps using ACEs and trauma-informed care: a resilience model.
AB  - This paper 1) discusses two important contributions that are shaping work with
      vulnerable and under-resourced populations: Kaiser Permanente's (1998) Adverse
      Childhood Experiences Study (ACE) which includes the impact of adverse
      experiences in childhood on adult health and health behaviors and the more recent
      advent of what has come to be known as Trauma-Informed Care (TIC), programs which
      incorporate knowledge of the impact of early trauma into policies and programs.
      2) Despite many positive benefits that have come from both contributions there
      are unintended consequences, described in the paper, that have an impact on
      research and program evaluation as well as social policies and programs. 3) Three
      key neuroscience concepts are recommended for inclusion in Trauma-Informed Care
      programs and practices in ways that can enrich program design and guide the
      development of practical, resilience-oriented interventions that can be evaluated
      for outcomes. 4) Finally, a resilience-oriented approach to TIC is recommended
      that moves from trauma information to neuroscience-based action with practical
      skills to build greater capacity for self-regulation and self-care in both
      service providers and clients. Examples from criminal justice are used.

PMID- 28455575
TI  - [Prophylaxis of infectious complications following prostate biopsy].
AB  - Different strategies have been developed to reduce infectious complications
      following prostate biopsy. Various technical aspects like number of biopsies,
      needle size, route of biopsy, periprostatic nerve blockade, rectal preparation by
      enema, or disinfection with povidone-iodine have to be discussed. Regarding
      antibiotic therapy, choosing the optimal antibiotic, the duration of prophylaxis,
      combination therapy, and rectal swab-based antimicrobial therapy are of major
      interest. The current review gives answers to the different aspects.

PMID- 28455576
TI  - [Pathogenesis of urinary tract infections : An update].
AB  - Urinary tract infections are among the most common bacterial infections
      worldwide. The management has become a public health concern of socioeconomic
      importance. Every second woman will experience at least one episode in her
      lifetime. Due to the emergence of multiresistant pathogens and the developmental
      void, treatment has become more challenging over the years. Deciphering the
      complex molecular interaction between host and pathogen is necessary to identify
      potent treatment targets for future approaches. The objective of this review is
      to present novel aspects on the pathogenesis of urinary tract infections and its
      relevance for clinical practice.

PMID- 28455577
TI  - [One decade of HPV vaccination in Germany].
AB  - As a worldwide very common sexually transmitted infection (STI), HPV causes
      millions of genital warts every year and is responsible for 5% of all cancers in
      men and women. With strong empirical evidence for both vaccine safety and
      efficacy, the HPV vaccines proved to protect against these HPV-related conditions
      over the last decade. But current HPV vaccination coverage is suboptimal in many
      countries. Even in Germany the absence of a school-based immunization program and
      the recommendation of a publicly funded girls-only HPV vaccination strategy are
      the main reasons for a female coverage rate under 40%, which does not achieve
      herd immunity for the boys. Therefore, the German immunization program urgently
      needs revision to fight an increasing number of young Germans missing out on the
      most important development in cancer prevention. Gender-neutral bundling of the
      HPV vaccine to other routinely recommended vaccines for preteens at one visit
      will have many advantages at the same time: Lowering the age of HPV vaccination
      to 9-12 years will improve the cost-effectiveness because a two-dose vaccination
      schedule is established on this score. Time-consuming and redundant explanations
      of the attending physician as well as parent's discussion on feeling stigmatized
      by the STI nature of HPV could be avoided in a combined vaccination setting. By
      expanding the HPV vaccination to boys, the resulting gender-neutral vaccination
      program can be cost-effective if all HPV-related diseases which can be prevented
      by vaccination are considered.

PMID- 28455579
TI  - [New microbiological techniques].
AB  - Microbiological diagnostic procedures have changed rapidly in recent years. This
      is especially true in the field of molecular diagnostics. Classical culture-based
      techniques are still the gold standard in many areas; however, they are already
      complemented by automated and also molecular techniques to guarantee faster and
      better quality results. The most commonly used techniques include real-time
      polymerase chain reaction (RT-PCR) based systems and nucleic acid hybridization.
      These procedures are used most powerfully from direct patient samples or in
      assays to detect the presence of nonculturable or fastidious organisms. Further
      techniques such as DNA sequencing are not yet used routinely for urological
      samples and can be considered experimental. However, in conjunction with dropping
      prices and further technical developments, these techniques promise to be used
      much more in the near future. Regarding bacterial identification from culture,
      mass spectrometry (MALDI-TOF MS) has become the technique of choice in recent
      years especially in Europe. It has tremendously shortened the time to result.
      This is now going to be extended to antibiotic susceptibility testing. This is of
      paramount importance in view of ever rising antimicrobial resistance rates.
      Techniques described in this review offer a faster and better microbiological
      diagnosis. Such continuous improvements are critical especially in times of cost
      pressure and rising antimicrobial resistance rates. It is in our interest to
      provide the best possible care for patients and in this regard a good and
      effective communication between the laboratory and the clinician is of vital
      importance.

PMID- 28455578
TI  - [Epidemiology, diagnostics, therapy, prevention and management of uncomplicated
      bacterial outpatient acquired urinary tract infections in adult patients : Update
      2017 of the interdisciplinary AWMF S3 guideline].
AB  - BACKGROUND: Update of the 2010 published evidence-based S3 guideline on
      epidemiology, diagnostics, therapy and management of uncomplicated, bacterial,
      outpatient-acquired urinary tract infections in adult patients. The guideline
      contains current evidence for the rational use of antimicrobial substances,
      avoidance of inappropriate use of certain antibiotic classes and development of
      resistance. METHODOLOGY: The update was created under the leadership of the
      German Association of Urology (DGU). A systematic literature search was conducted
      for the period 01 January 2008 to 31 December 2015. International guidelines have
      also been taken into account. Evidence level and risk of bias were used for
      quality review. RESULTS: Updated information on bacterial susceptibility,
      success, collateral damage and safety of first- and second-line antibiotics was
      given. For the treatment of uncomplicated cystitis the first line antibiotics are
      fosfomycin trometamol, nitrofurantoin, nitroxoline, pivmecillinam, trimethoprim
      (with consideration of the local resistance rates). Fluoroquinolones and
      cephalosporins should not be used as first choice antibiotics. In the case of
      uncomplicated pyelonephritis of mild to moderate forms, preferably cefpodoxime,
      ceftibuten, ciprofloxacin or levofloxacin should be used as oral antibiotics.
      CONCLUSION: The updated German S3 guideline provides comprehensive evidence- and
      consensus-based recommendations on epidemiology, diagnostics, therapy, prevention
      and management of uncomplicated bacterial outpatient acquired urinary tract
      infections in adult patients. Antibiotic stewardship aspects have significantly
      influenced the therapeutic recommendations. A broad implementation in all
      clinical practice settings is necessary to ensure a foresighted antibiotic policy
      and thus t improve clinical care.

PMID- 28455581
TI  - Frozen-thawed blastocyst transfer in natural cycle: feasibility in everyday
      clinical practice.
AB  - PURPOSE: Transfer of frozen-thawed embryos in natural cycle is gaining consensus
      but evidence on this approach is scanty. The aim of this study is reporting on
      the feasibility of this type of policy in everyday clinical practice. METHODS: We
      retrospectively selected all women undergoing the procedure between July 2013 and
      December 2014. During the study period, women were systematically scheduled for
      natural cycle if they referred regular menstrual cycles. Hormone replacement
      therapy (HRT) was conversely prescribed if the woman had irregular menstrual
      cycles or if the monitoring of the natural cycle failed. The analysis exclusively
      focussed on the first cycle per woman. RESULTS: Overall, 251 women were selected.
      HRT was initially chosen in 52 women, leaving 199 women suitable for the natural
      cycle. This procedure could be performed in 194 of these women (97%, 95% CI 95
      99%). Two additional women initially allocated to HRT ultimately performed the
      blastocyst transfer with natural cycle. Overall, 196 were thus treated with
      natural cycle (78%, 95% CI 73-83%). The basal characteristics of the women who
      did and did not undergo natural cycles were similar with the exceptions of serum
      FSH (p < 0.001) and AMH (p = 0.03). The live birth rate did not also differ (34%
      versus 31%, p = 0.63). Characteristics of women treated with the natural cycle
      who did (n = 67) and did not (n = 129) achieve a live birth did not differ.
      CONCLUSION: Frozen-thawed blastocyst transfer in natural cycle can be
      successfully performed in the vast majority of women.

PMID- 28455580
TI  - Cardiovascular risk in patients with rheumatoid arthritis.
AB  - Substantial epidemiologic data have shown an increased risk of cardiovascular
      (CV) disease in rheumatoid arthritis (RA) patients. Traditional CV risk factors
      may partly contribute to CV disease in RA; however, current evidence underlines
      the important role of inflammation in the pathogenesis of atherosclerosis and
      amplification of CV risk. Interplays between inflammation and lipid metabolism in
      the development of atherosclerosis have been established by recent scientific
      advances. Atherosclerosis is currently viewed as an inflammatory disease, and
      modifications of lipoproteins during inflammation accelerate atherogenesis. The
      role of inflammation in the increased CV risk in RA has been further demonstrated
      by the CV protective effect of methotrexate and TNF antagonists, particularly in
      patients responding to these treatments. The management of CV risk in RA should
      include the use of effective disease-modifying anti-rheumatic drugs to control
      disease activity and the treatment of traditional CV risk factors.

PMID- 28455582
TI  - Glutathione S-transferases deletions may act as prognosis and therapeutic markers
      in breast cancer.
AB  - Breast cancer (BC) is the main worldwide neoplasia in women. The metabolic
      balance between xenobiotic absorption and elimination rates plays an important
      role in preventing DNA damage and, consequently, tumor development. The
      glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the NAD(P)H
      quinone oxidoreductase are important enzymes involved in phase II detoxification
      reactions. Deletions in GSTM1 and GSTT1, and single-nucleotide polymorphism (SNP)
      in NQO1 (rs1800655) have been investigated in cancer context, revealing
      conflicting results. The present study analyzed these genetic polymorphisms in
      121 BC patients and 151 BC-free controls in order to verify if they could act as
      susceptibility modifiers and/or prognostic factors. Binary logistic regressions
      adjusted by age were performed to assess associations between allelic variants
      and interactions in polymorphisms combination with BC susceptibility, but no
      significant association was found. Genotypes distribution was also compared
      between BC subtypes, but no significant difference was observed (p > 0.05). GSTM1
      deletion was significantly associated with histopathological grade, with a
      greater proportion of patients presenting grade III tumors (p = 0.007).
      Univariate analysis identified tumor size as the only clinicopathological
      parameter potentially associated with recurrence risk in patients that received
      adjuvant chemotherapy (p < 0.1). Thus, logistic regression analysis adjusted by
      tumor size revealed a positive association between GSTT1 deletion and recurrence
      risk in general BC (OR 4.25; p = 0.04), while GSTM1 was negatively associated
      with recurrence risk in ER/PR+HER2- samples (OR 0.07; p = 0.03). In conclusion,
      the present study indicated that GSTT1 deletion was associated with increased
      recurrence risk, while GSTM1 correlated with worst prognosis parameters at
      diagnosis, but was negatively associated with recurrence risk in luminal subtype
      samples.

PMID- 28455583
TI  - Neurotoxicity after high-dose methotrexate (MTX) is adequately explained by
      insufficient folinic acid rescue.
AB  - PURPOSE: To challenge the view that the dose of folinic acid rescue after high
      dose methotrexate (MTX) has no significance in the prevention of neurotoxicity
      and to present the minority view that neurotoxicity can be prevented by an
      adequate dose of folinic acid, without compromising treatment results. Several
      fallacies that led to the misunderstanding of post MTX neurotoxicity are
      presented. METHODS: Data mining using search engines was used to find relevant
      publications, and an e-mail survey of more than 60 authors of articles in this
      field was performed. All relevant articles identified were read in their
      entirety. RESULTS: Examples of clinical studies with neurotoxicity following
      inadequate rescue are given. Some studies demonstrated no neurotoxicity when
      adequate doses of folinic acid rescue were started 24-36 h after the start of
      HDMTX rescue even after mega doses of MTX. Rescue started after 42 h was
      associated with neurotoxicity except in patients with low serum MTX levels after
      24 and 36 h. ALL protocols with neurotoxicity, especially BFM-like protocols, are
      presented. Protocol is reported in which single protocol changes prevented
      neurotoxicity. CONCLUSIONS: From the published data, when folinic acid rescue is
      given in a sufficiently high enough dose and is started 24-36 h after the
      beginning of the methotrexate exposure, and virtually all forms of post MTX
      neurotoxicity can be prevented without compromising therapeutic results.

PMID- 28455584
TI  - Phase II study of S-1 plus bevacizumab combination therapy for patients
      previously treated for non-squamous non-small cell lung cancer.
AB  - PURPOSE: To assess the efficacy and toxicity of S-1 and bevacizumab combination
      therapy for patients previously treated for advanced non-squamous non-small cell
      lung cancer (NSCLC). METHODS: This was a prospective, multi-center, single-arm
      phase II study. Patients with non-squamous NSCLC who had experienced progression
      after cytotoxic chemotherapy were enrolled. Oral S-1 was administered on days 1
      14 of a 21-day cycle, and bevacizumab (15 mg/kg) was given intravenously on day
      1. Patients received S-1 adjusted on the basis of their creatinine clearance and
      body surface area. The primary endpoint was response rate (RR); secondary
      endpoints were progression-free survival (PFS), overall survival (OS), and
      safety. RESULTS: We enrolled 30 patients. One patient had never received platinum
      based therapy. Five patients had activating mutations of the epidermal growth
      factor receptor gene, of whom four had received tyrosine kinase inhibitors before
      this study. The RR was 6.7% [95% confidence interval (CI) 1.8-21.3%], and the
      disease control rate (DCR) was 80% (95% CI 62.7-90.5%). Median PFS was 4.8 months
      (95% CI 2.7-6.4 months], and median OS was 13.8 months (95% CI 8.4 months-not
      applicable). Patients did not experience any Grade 4 toxicity or treatment
      related death. Grade 3 hematologic toxicity (anemia) occurred in one patient
      (3.3%). The main Grade 3 non-hematologic toxicities were anorexia (10%),
      infection (10%), and diarrhea (6.7%). CONCLUSION: The addition of bevacizumab to
      S-1 was tolerable, but not beneficial for patients with previously treated non
      squamous NSCLC. We do not recommend further study of this regimen.

PMID- 28455585
TI  - The incidence and risk factors of febrile neutropenia in chemotherapy-naive lung
      cancer patients receiving etoposide plus platinum.
AB  - PURPOSE: This study was to determine the incidence and risk factors of febrile
      neutropenia in chemotherapy-naive Japanese patients treated systemically with
      etoposide plus platinum for lung cancer. METHODS: The study was a retrospective
      analysis of 244 patients who were monitored for febrile neutropenia through
      multiple cycles of the combination of etoposide with platinum, and the
      associations between incidence of febrile neutropenia and patient characteristics
      were evaluated. RESULTS: Eighty-eight patients were treated with etoposide plus
      cisplatin and 156 were treated with etoposide plus carboplatin. Of the 244
      patients treated, 198 (81.1%) completed 4 cycles for chemotherapy. Febrile
      neutropenia was observed in 48 of 244 patients (19.7%), including 18 of 88
      (20.5%) patients who received etoposide plus cisplatin and 30 of 156 (19.2%)
      patients who received etoposide plus carboplatin. Grade 3 or 4 of neutropenia was
      experienced by a total of 208 patients (85.2%); 79 of 88 (89.8%) receiving
      etoposide plus cisplatin and 129 of 156 (82.7%) receiving etoposide plus
      carboplatin. Male gender and previous radiotherapy were identified by
      multivariate analysis as independent risk factors for febrile neutropenia.
      CONCLUSIONS: These results contrast with findings in Western patients and suggest
      that ethnic differences exist in the incidence of febrile neutropenia in patients
      receiving etoposide plus platinum chemotherapy. In addition, our results suggest
      that primary prophylaxis with granulocyte colony-stimulating factor should be
      considered for patients with these risk factors for febrile neutropenia prior to
      treatment with etoposide plus platinum.

PMID- 28455586
TI  - Primary lymphocyte infection models for KSHV and its putative tumorigenesis
      mechanisms in B cell lymphomas.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the latest addition to the
      human herpesvirus family. Unlike alpha- and beta-herpesvirus subfamily members,
      gamma-herpesviruses, including Epstein-Barr virus (EBV) and KSHV, cause various
      tumors in humans. KSHV primarily infects endothelial and B cells in vivo, and is
      associated with at least three malignancies: Kaposi's sarcoma and two B cell
      lymphomas, respectively. Although KSHV readily infects endothelial cells in vitro
      and thus its pathogenic mechanisms have been extensively studied, B cells had
      been refractory to KSHV infection. As such, functions of KSHV genes have mostly
      been elucidated in endothelial cells in the context of viral infection but not in
      B cells. Whether KSHV oncogenes, defined in endothelial cells, play the same
      roles in the tumorigenesis of B cells remains an open question. Only recently,
      through a few ground-breaking studies, B cell infection models have been
      established. In this review, those models will be compared and contrasted and
      putative mechanisms of KSHV-induced B cell transformation will be discussed.

PMID- 28455587
TI  - Comprehensive analysis of fungal diversity and enzyme activity in nuruk, a Korean
      fermenting starter, for acquiring useful fungi.
AB  - Nuruk is a fermenting starter that is involved in the production of alcoholic
      beverages, and has been used in South Korea for a very long time. To analyze the
      fungal diversity, we collected a total of 59 nuruk samples from several companies
      and persons in 2013 to 2014, and obtained 364 isolates. All of the single
      isolated fungi were identified, both morphologically and molecularly, based on
      the sequences of ribosomal RNA gene [18S, ITS1-5.8S-ITS2, and 26S (D1/D2
      region)]. In 46 nuruk samples out of 59 (78%), Saccharomycopsis fibuligera, a
      dimorphic yeast, was most frequently isolated. Among the filamentous fungi,
      Aspergillus and Lichtheimia were found in more than 50% of the samples with lower
      colony forming unit (CFU/g of sample) than those of yeasts. The yeasts S.
      fibuligera and Wickerhamomyces anomalus were counted with maximum 1.3-1.8 * 108
      CFU/g. Among Mucorales fungi, Lichtheimia and Mucor were isolated in much higher
      numbers than Rhizopus and Rhizomucor. Overall, the home-made nuruks tend to
      contain more diverse filamentous fungi than the commercial nuruks. To acquire
      industrially useful filamentous fungi and yeasts, we analyzed the enzyme
      activities of alpha-amylase, glucoamylase and acid protease associated with
      brewing properties for 131 strains. Aspergillus oryzae and S. fibuligera had high
      alpha- and glucoamylase activities and most isolates of Lichtheimia ramosa had
      high acid protease activity. For further applications, 27 fungal strains were
      chosen based on isolation frequencies from nuruk, and the ability to produce
      useful enzyme.

PMID- 28455588
TI  - A diversity study of Saccharomycopsis fibuligera in rice wine starter nuruk,
      reveals the evolutionary process associated with its interspecies hybrid.
AB  - The amylolytic yeast Saccharomycopsis fibuligera is the predominant yeast in the
      starter product, nuruk, which is utilized for rice wine production in South
      Korea. Latest molecular studies explore a recently developed interspecific
      hybridization among stains of S. fibuligera with a unique genetic feature.
      However, the origin of the natural hybridization occurrence is still unclear.
      Thus, to respectively distinguish parental and hybrid strains, specific primer
      sets were applied on 141 yeast strains isolated from different nuruk samples
      fermented in different provinces. Sixty-seven strains were defined accordingly as
      parental species with genome A while 8 strains were defined as hybrid strains.
      Unexpectedly, another parental species with genome B could not be found among the
      strain pools yet. Furthermore, it was observed that hybrid strains are
      phenotypically different from A genome strains; asci containing tetrad ascospores
      were observed in A genome strains more frequent than in hybrid strains.
      Nevertheless, hybrid strains were slightly more thermotolerant than A genome
      strains. Interestingly, all hybrid strains were located only in Jeju province.
      Based on these sets of data, we speculated that the unique climate of Jeju
      province might play an evolutionary role in the interspecific hybridization
      between A genome strains, as well as the unculturable allopatric B genome
      strains.

PMID- 28455589
TI  - N-acetylcysteine prevents the development of gastritis induced by Helicobacter
      pylori infection.
AB  - Helicobacter pylori (H. pylori) is a human gastric pathogen, causing various
      gastric diseases ranging from gastritis to gastric adenocarcinoma. It has been
      reported that combining N-acetylcysteine (NAC) with conventional antibiotic
      therapy increases the success rate of H. pylori eradication. We evaluated the
      effect of NAC itself on the growth and colonization of H. pylori, and development
      of gastritis, using in vitro liquid culture system and in vivo animal models. H.
      pylori growth was evaluated in broth culture containing NAC. The H. pylori load
      and histopathological scores of stomachs were measured in Mongolian gerbils
      infected with H. pylori strain 7.13, and fed with NAC-containing diet. In liquid
      culture, NAC inhibited H. pylori growth in a concentration-dependent manner. In
      the animal model, 3-day administration of NAC after 1 week from infection reduced
      the H. pylori load; 6-week administration of NAC after 1 week from infection
      prevented the development of gastritis and reduced H. pylori colonization.
      However, no reduction in the bacterial load or degree of gastritis was observed
      with a 6-week administration of NAC following 6-week infection period. Our
      results indicate that NAC may exert a beneficial effect on reduction of bacterial
      colonization, and prevents the development of severe inflammation, in people with
      initial asymptomatic or mild H. pylori infection.

PMID- 28455590
TI  - Crystal structure of Streptomyces coelicolor RraAS2, an unusual member of the
      RNase E inhibitor RraA protein family.
AB  - Bacterial ribonuclease E (RNase E) plays a crucial role in the processing and
      decay of RNAs. A small protein named RraA negatively regulates the activity of
      RNase E via protein-protein interaction in various bacteria. Recently, RraAS1 and
      RraAS2, which are functional homologs of RraA from Escherichia coli, were
      identified in the Gram-positive species Streptomyces coelicolor. RraAS1 and
      RraAS2 inhibit RNase ES ribonuclease activity in S. coelicolor. RraAS1 and RraAS2
      have a C-terminal extension region unlike typical bacterial RraA proteins. In
      this study, we present the crystal structure of RraAS2, exhibiting a hexamer
      arranged in a dimer of trimers, consistent with size exclusion chromatographic
      results. Importantly, the C-terminal extension region formed a long alpha-helix
      at the junction of the neighboring subunit, which is similar to the trimeric RraA
      orthologs from Saccharomyces cerevisiae. Truncation of the C-terminal extension
      region resulted in loss of RNase ES inhibition, demonstrating its crucial role.
      Our findings present the first bacterial RraA that has a hexameric assembly with
      a C-terminal extension alpha-helical region, which plays an essential role in the
      regulation of RNase ES activity in S. coelicolor.

PMID- 28455591
TI  - Mutational analysis of the RNA helicase Dhh1 in Ste12 expression and yeast
      mating.
AB  - Dhh1 and Dhh1 homologues (RCK/p54/DDX6) are members of the DEAD-box protein
      family of RNA helicases. These proteins display conserved sequence motifs for
      ATPase and RNA binding activities. Dhh1 is a component of the P-bodies
      (processing bodies) of mRNA granules and functions as an mRNA decapping activator
      in Saccharomyces cerevisiae. Dhh1 also contributes to gene-specific regulation
      during yeast mating. The dhh1 deletion mutation results in a significant decrease
      in the expression of Ste12, a mating-specific transcription factor, showing
      severe mating defects. Here, we introduced amino-acid substitution mutations in
      the ATPase and RNA binding domains of Dhh1 and also constructed a deletion of 79
      amino acids at the Q/P-rich C-terminal region. The mutations in ATPase A and B
      motif (K96R, D195A) and C-terminus deletion showed reduced levels of mating
      efficiency as well as Ste12 protein expression. The Q/P-rich C-terminal region of
      Dhh1 was dispensable for growth at nonpermissive temperature 37 degrees C but
      appeared to play an important role in regulating the Ste12 protein expression and
      mating processes. The P-body accumulation induced by treatment with alpha-mating
      factor required ATPase, RNA-binding and the Q/P-rich C-terminal domains of Dhh1.

PMID- 28455592
TI  - [88th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and
      Neck Surgery : With good hearing and without vertigo through everyday life-but
      how?]

PMID- 28455593
TI  - ?

PMID- 28455594
TI  - [Polyneuropathy in the elderly].
AB  - The peripheral nervous system is subject to changes during the ageing process, e.
      g. deep tendon reflexes decrease, as does proprioception. Polyneuropathies, on
      the other hand, need to be distinguished from age-related changes as independent
      diseases with etiologies similar to those at younger ages. Etiologies includes
      metabolic disorders, primary inflammatory polyneuropathies, and systemic
      disorders. Neuropathies associated with diabetes, malignancy, and monoclonal
      gammopathies appear to be more common in older patients. Using a systematic
      approach, it is possible to establish a specific diagnosis in the majority of
      cases. Since polyneuropathies contribute to reduced mobility in the elderly, an
      assessment of functional skills is mandatory. Polyneuropathy therapy is primarily
      based on the treatment of underlying conditions and neuropathic pain management.
      Physiotherapy and rehabilitation target pain relief and maintaining activities of
      daily living.

PMID- 28455595
TI  - CREBH mediates metabolic inflammation to hepatic VLDL overproduction and
      hyperlipoproteinemia.
AB  - : Metabolic inflammation is closely associated with hyperlipidemia and
      cardiovascular disease. However, the underlying mechanisms are not fully
      understood. The current study established that cAMP-responsive-element-binding
      protein H (CREBH), an acute-phase transcription factor, enhances very-low-density
      lipoprotein (VLDL) assembly and secretion by upregulating apolipoprotein B (apoB)
      expression and contributes to metabolic inflammation-associated
      hyperlipoproteinemia induced by TNFalpha, lipopolysaccharides (LPS), and high-fat
      diet (HFD) in mice. Specifically, overexpression of CREBH significantly induced
      mRNA and protein expression of apoB in McA-7777 cells. Luciferase assay further
      revealed that the presence of CREBH could significantly increase the activity of
      the apoB gene promoter. In contrast, genetic depletion of CREBH in mice resulted
      in significant reduction in expression of hepatic apoB mRNA. Challenging mice
      with an acute fat load led to upregulation of triglyceride (TG)-rich lipoprotein
      secretion in wild type mice, but not in CREBH-null mice. TNFalpha treatment
      activated hepatic CREBH expression, which in turn enhanced hepatic apoB
      biosynthesis and VLDL secretion. Metabolic inflammation induced by LPS or HFD
      also resulted in overproduction of apoB and hyperlipoproteinemia in wild type
      mice, but not in CREBH-null mice. This study demonstrates that CREBH could be a
      mediator between metabolic inflammation and hepatic VLDL overproduction in
      chronic metabolic disorders. This novel finding establishes CREBH as the first
      transcription factor that regulates apoB expression on the transcriptional level
      and the subsequent VLDL biosynthesis in response to metabolic inflammation. The
      study also provides novel insight into the pathogenesis of hyperlipidemia in
      metabolic syndrome. KEY MESSAGES: CREBH mediates inflammatory signaling to VLDL
      overproduction in metabolic stress. Activation of CREBH in inflammation enhances
      mRNA and protein expression of apoB. CREBH presents a potential novel therapeutic
      target for hyperlipoproteinemia.

PMID- 28455596
TI  - Clinical decision support systems in child and adolescent psychiatry: a
      systematic review.
AB  - Psychiatric disorders are amongst the most prevalent and impairing conditions in
      childhood and adolescence. Unfortunately, it is well known that general
      practitioners (GPs) and other frontline health providers (i.e., child protection
      workers, public health nurses, and pediatricians) are not adequately trained to
      address these ubiquitous problems (Braddick et al. Child and Adolescent mental
      health in Europe: infrastructures, policy and programmes, European Communities,
      2009; Levav et al. Eur Child Adolesc Psychiatry 13:395-401, 2004). Advances in
      technology may offer a solution to this problem with clinical decision support
      systems (CDSS) that are designed to help professionals make sound clinical
      decisions in real time. This paper offers a systematic review of currently
      available CDSS for child and adolescent mental health disorders prepared
      according to the PRISMA-Protocols (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses Protocols). Applying strict eligibility criteria, the
      identified studies (n = 5048) were screened. Ten studies, describing eight
      original clinical decision support systems for child and adolescent psychiatric
      disorders, fulfilled inclusion criteria. Based on this systematic review, there
      appears to be a need for a new, readily available CDSS for child neuropsychiatric
      disorder which promotes evidence-based, best practices, while enabling
      consideration of national variation in practices by leveraging data-reuse to
      generate predictions regarding treatment outcome, addressing a broader cluster of
      clinical disorders, and targeting frontline practice environments.

PMID- 28455597
TI  - Association of digitalis treatment with outcomes following myocardial infarction
      in patients with heart failure or evidence of left ventricular dysfunction: an
      analysis from the High-Risk Myocardial Infarction Database Initiative.
AB  - BACKGROUND: Contradictory findings have been reported regarding the safety and
      efficacy of digitalis in patients recovering from acute myocardial infarction
      (MI). We studied the association of digitalis use with long-term and short-term
      prognosis in patients presenting with an acute MI complicated with heart failure
      (HF), left ventricular dysfunction, or both. METHODS AND RESULTS: Using the High
      Risk MI Database Initiative combining data from 4 major clinical trials, totaling
      27,673 patients, we investigated the association between digitalis use at
      baseline (3093 patients with digitalis and 24,580 without) with the rate of all
      cause death, sudden cardiac death, cardiovascular death, HF hospitalization and
      the combination of the latter two, over a mean follow-up time of 2.7 years.
      Patients with and without atrial fibrillation (AF) were studied separately. After
      a propensity score-based analysis, among patients without AF, those receiving
      digitalis experienced a higher rate of all-cause [hazard ratio (HR) 1.54, 95%
      confidence interval (CI) 1.42-1.67] and sudden cardiac death (HR 1.65, 95% CI
      1.44-1.89), compared to those not receiving digitalis; similar results were found
      for the other 3 endpoints (all HR around 1.6). In contrast, in AF patients,
      digitalis had a milder effect on all outcomes (all HR <= 1.12), with significant
      association only for the composite endpoint (HR 1.10, 95% CI 1.00-1.21, p =
      0.049); comparable results were obtained at 30 days. Finally, the detrimental
      effect associated with digitalis use appeared to be more pronounced in patients
      with ejection fraction >= 40%. CONCLUSIONS: In MI survivors with HF and/or
      systolic dysfunction, digitalis was associated with a significant increased risk
      of death in patients without AF with mild to neutral associations for patients
      with AF. These findings raise concerns regarding the safety of digitalis in MI
      survivors with HF, especially for those without AF.

PMID- 28455598
TI  - A lateral paracarotid approach for ultrasound-guided stellate ganglion block with
      a linear probe.
AB  - Recent reports suggest that ultrasound-guided stellate ganglion block (SGB) is
      safer and more accurate than classic SGB by the using the surface anatomical
      landmark. However, previous reports concern the classic paratracheal approach
      using a small specialized curved probe, which may not be appropriate in some
      patients. The authors have attempted several approaches, including paratracheal,
      trans-thyroidal, lateral paracarotid, and lateral approaches, to find a safe and
      suitable method for real-time ultrasound-guided SGB using a standard high
      frequency linear probe. A total of 27 injections were performed on 27 patients
      with sensorineural hearing loss. The lateral paracarotid out-of-plane and lateral
      in-plane approaches were identified as the easiest and safest methods among the
      four tested. In this report, we describe a new lateral paracarotid approach for
      ultrasound-guided SGB. An ipsilateral paratracheal short-axis transverse scan was
      acquired at the C6 level with a linear probe (6-13 MHz). The probe was moved
      laterally, scanning the thyroid, carotid artery, internal jugular vein, longus
      colli muscle, and the transverse process of the C6, placing the carotid artery in
      the middle of the view. Light pressure was applied to the probe postero-medially
      to displace the carotid artery medially and completely compress the internal
      jugular vein. The needle was inserted out-of-plane between the lateral margin of
      the carotid artery and Chassaignac's tubercle, traversing the collapsed internal
      jugular vein, and targeted between the longus colli muscle and the prevertebral
      fascia. A total of 4 ml of 0.2% ropivacaine was injected for each procedure after
      a negative aspiration test. Successful blockade was confirmed with the onset of
      Horner's sign. All 27 injections resulted in successful blockade with Horner's
      sign presenting within 5 min after injection. Side effects were minor and caused
      minimal discomfort; they included hoarseness and a foreign body sensation. No
      hematomas formed after any injections. We suggest that this new lateral
      paracarotid approach, with out-of plane needle insertion at the C6 tubercle under
      transverse scan, is a convenient and safe method for performing real-time
      ultrasound-guided SGB, as it provides a wide, safe space for needle passage
      without risking thyroid or esophageal injury.

PMID- 28455599
TI  - An update on the management of postoperative nausea and vomiting.
AB  - Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting
      (PDNV) remain common and distressing complications following surgery. PONV and
      PDNV can delay discharge and recovery and increase medical costs. The high
      incidence of PONV has persisted in part because of the tremendous growth in
      ambulatory surgery and the increased emphasis on earlier mobilization and
      discharge after both minor and major operations. Pharmacological management of
      PONV should be tailored to the patients' risk level using the PONV and PDNV
      scoring systems to minimize the potential for these adverse side effects in the
      postoperative period. A combination of prophylactic antiemetic drugs should be
      administered to patients with moderate-to-high risk of developing PONV in order
      to facilitate the recovery process. Optimal management of perioperative pain
      using opioid-sparing multimodal analgesic techniques and preventing PONV using
      prophylactic antiemetics are key elements for achieving an enhanced recovery
      after surgery. Strategies that include reductions of the baseline risk (e.g.,
      adequate hydration, use of opioid-sparing analgesic techniques) as well as a
      multimodal antiemetic regimen will improve the likelihood of preventing both PONV
      and PDNV.

PMID- 28455600
TI  - Protective multimodal analgesia with etoricoxib and spinal anesthesia in inguinal
      hernia repair: a randomized controlled trial.
AB  - BACKGROUND: Inguinal hernia repair is a common procedure, and can be performed
      under spinal anesthesia. Although adequate analgesia is crucial to postoperative
      recovery, the optimal protective analgesic regimen remains to be established.
      PURPOSE: To investigate the effects of preoperative etoricoxib within a
      protective multimodal analgesic regimen with respect to pain control following
      open inguinal hernia repair. METHODS: Sixty adult patients undergoing open
      inguinal hernia repair participated in a single-center, randomized, double
      blinded, placebo-controlled trial in a general academic medical center. The
      intervention group (n = 30) received 120 mg of oral etoricoxib 1 h
      preoperatively, and 10-12 mg bupivacaine with 25 MUg fentanyl as spinal
      anesthesia. The control group (n = 30) received oral placebo 1 h preoperatively,
      and spinal anesthesia as above. Postoperative Visual Analog Scale pain scores at
      rest and on active straight leg raise were recorded and analyzed. RESULTS:
      Resting pain scores were significantly lower in the intervention than the control
      group at 16 h, 24 h, and on discharge (3.00 vs. 4.35; 1.57 vs. 4.00; 1.24 vs.
      3.76, respectively; p < 0.05). Pain scores on active straight leg raise were
      significantly lower in the intervention than the control group at 16 h, 24 h, and
      on discharge (3.85 vs. 5.59, p < 0.01; 2.84 vs. 4.90, p < 0.05; 3.55 vs. 5.32, p
      < 0.05, respectively). CONCLUSION: The addition of etoricoxib to spinal
      anesthesia as a multimodal protective regimen can improve pain control after
      inguinal hernia repair. The optimal dose and applicability to other operations
      remains to be established.

PMID- 28455601
TI  - Paravertebral block catheter breakage by electrocautery during thoracic surgery.
AB  - Advantages of thoracic paravertebral analgesia (TPA) include placement of the
      catheter closer to the surgical field; however, the catheter can become damaged
      during the operation. We experienced a case of intraoperative TPA catheter
      breakage that prompted us to perform an experiment to investigate possible
      causes. A 50-year-old male underwent a thoracoscopic lower lobectomy under
      general anesthesia with TPA via an intercostal approach. Following surgery, it
      was discovered that the catheter had become occluded, as well as cut and fused,
      so we reopened the incision and removed the residual catheter. From that
      experience, we performed an experiment to examine electrocautery-induced damage
      in normal (PortexTM, Smith's Medical), radiopaque (Perifix SoftTipTM, BBraun),
      and reinforced (Perifix FXTM, BBraun) epidural catheters (n = 8 each). Chicken
      meat was penetrated by each catheter and then cut by electrocautery. In the
      normal group, breakage occurred in 8 and occlusion in 6 of the catheters, and in
      the radiopaque group breakage occurred in 8 and occlusion in 7. In contrast,
      breakage occurred in only 3 and occlusion in none in the reinforced group, with
      the 5 without breakage remaining connected only by the spring coil. Furthermore,
      in 7 of the reinforced catheters, electric arc-induced thermal damage was
      observed at the tip of the catheter. A TPA catheter for thoracic surgery should
      be inserted via the median approach, or it should be inserted after surgery to
      avoid catheter damage during surgery.

PMID- 28455602
TI  - Comparison of the incidences of hyponatremia in adult postoperative critically
      ill patients receiving intravenous maintenance fluids with 140 mmol/L or 35
      mmol/L of sodium: retrospective before/after observational study.
AB  - PURPOSE: The purpose of this study was to compare the incidences of hyponatremia
      in adult postoperative critically ill patients receiving isotonic and hypotonic
      maintenance fluids. METHODS: In this single-center retrospective before/after
      observational study, we included patients who had undergone an elective operation
      for esophageal cancer or for head and neck cancer and who received postoperative
      intensive care for >48 h from August 2014 to July 2016. In those patients, sodium
      poor solution (35 mmol/L of sodium; Na35) had been administered as maintenance
      fluid until July 2015. From August 2015, the protocol for postoperative
      maintenance fluid was revised to the use of isotonic fluid (140 mmol/L of sodium;
      Na140). The primary outcome was the incidence of hyponatremia (<135 mmol/L) until
      the morning of postoperative day (POD) 2. RESULTS: We included 179 patients
      (Na35: 87 patients, Na140: 92 patients) in the current study. The mean volume of
      fluid received from ICU admission to POD 2 was not significantly different
      between the two groups (3291 vs 3337 mL, p = 0.84). The incidence of
      postoperative hyponatremia was 16.3% (15/92) in the Na140 cohort, which was
      significantly lower than that of 52.9% (46/87) in the Na35 group (odds ratio =
      0.17, 95% confidence interval 0.09-0.35, p < 0.001]. The incidences of
      hypernatremia, defined as serum sodium concentration >145 mmol/L, were not
      significantly different between the two groups. CONCLUSION: In this study, the
      use of intravenous maintenance fluid with 35 mmol/L of sodium was significantly
      associated with an increased risk of hyponatremia compared to that with 140
      mmol/L of sodium in adult postoperative critically ill patients.

PMID- 28455603
TI  - An Active Drimane-Type Lactone from Polygonum jucundum Attenuates
      Lipopolysaccharide-Induced Acute Lung Injury in Mice Through TLR4-MAPKs Signaling
      Pathway.
AB  - The herbs of Polygonum jucundum Lindex. (Polygonaceae) is a traditional Chinese
      medicine for inflammatory diseases. 2alpha-Hydroxyl-3beta-angeloylcinnamolide
      (HAC), a drimane-type sesquiterpenoid, was the major active compound of the
      ethanol extract of P. jucundum which inhibited the production of inflammatory
      mediators. However, the biological mechanism of HAC for anti-inflammatory
      activity has not been reported. In the current study, we investigated whether HAC
      could suppress the production of inflammatory mediators in lipopolysaccharide
      (LPS)-induced acute lung injury in mice (ALI) through downregulation of Toll-like
      receptor 4 (TLR4) and activations of mitogen-activated protein kinases (MAPKs)
      and inducible protein nitric oxide synthase (iNOS). Moreover, our data indicated
      that HAC inhibits the overexpression of iNOS and TLR4 in LPS-treated RAW264.7,
      and also inhibits MAPK signal. These findings suggest that HAC shows anti
      inflammatory effects in ALI mice through suppressing TLR4-mediated MAPK pathway
      in activated macrophages. In addition, six derivatives of HAC obtained by
      structure modification were investigated for their inhibitory effects on the
      production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha),
      suggesting that the acetylation could increase the inhibition of HAC on TNF-alpha
      release in LPS-treated RAW264.7 cells. In summary, all these results showed that
      HAC may be a potential anti-inflammatory lead compound for the treatment of acute
      lung injury.

PMID- 28455604
TI  - Biological incorporation of human acellular dermal matrix used in Achilles tendon
      repair.
AB  - Human acellular dermal matrices (ADMs) are used successfully in a variety of
      procedures, including sports medicine related, wound repair, and breast
      reconstructions, but the mechanism of repair is still not fully understood. An
      opportunity to explore this mechanism presented itself when a patient experienced
      a rerupture of the native tendon due to a fall that occurred 2 months after
      undergoing an Achilles tendon repair using Matracell treated ADM. The ADM was
      removed and an extensive histology analysis was performed on the tissue.
      Additionally, a literature review was conducted to determine the mechanism of ADM
      integration into the tendon structure and explore if differences in this
      mechanism exist for different types of human ADMS. The histology analysis
      demonstrated that the healing process during a tendon reconstruction procedure is
      similar to that of wound healing. Furthermore, the literature review showed that
      differences exist in the mechanism for integration among various human ADMs and
      that these differences may be due to variances in the methods and technologies
      that manufactures use to process human ADMs.

PMID- 28455605
TI  - How Can Geography and Mobile Phones Contribute to Psychotherapy?
AB  - Interdisciplinary relationships between Geography and Psychotherapy are an
      opportunity for innovation. Indeed, scientific works found on bibliographic
      databases and concerning this theme are scarce. Geographical sub-fields, such as
      the Geography of Emotions or Psychoanalytical Geography have started to emerge,
      theorizing about and interpreting feelings, emotions, moods, sufferings, of the
      chronically ill or diversified social groups and sites. But a less theoretical
      and more practical approach, in the sense of proposing, predicting and
      intervening, is lacking; as well as research into the possibilities offered by
      communication technologies and mobile phones. In the present work, we present the
      results of a review of the most relevant scientific works published
      internationally; we reflect on the contributions of Geography and mobile phones
      to psychosocial therapies and define the orientation and questions that should be
      posed in future research, from the point of view of geography and regarding
      psychotherapy. We conclude that the production of georeferenced data via mobile
      phones concerning the daily lives of people opens great possibilities for
      cognitive behavioural therapy and mental health. They allow for the development
      of personalized mood maps that locate the places where a person experiences
      greater or lesser stress on a daily basis; they allow for a cartography of
      emotions, a cognitive cartography of the places we access physically or through
      the Internet, of our feelings and psychosocial experiences. They open the door to
      the possibility of offering personalized psychotherapy treatments focusing on the
      ecological-environmental analysis of the places frequented by the person on a
      daily basis.

PMID- 28455606
TI  - Using Social Media to Identify Sources of Healthy Food in Urban Neighborhoods.
AB  - An established body of research has used secondary data sources (such as
      proprietary business databases) to demonstrate the importance of the neighborhood
      food environment for multiple health outcomes. However, documenting food
      availability using secondary sources in low-income urban neighborhoods can be
      particularly challenging since small businesses play a crucial role in food
      availability. These small businesses are typically underrepresented in national
      databases, which rely on secondary sources to develop data for marketing
      purposes. Using social media and other crowdsourced data to account for these
      smaller businesses holds promise, but the quality of these data remains unknown.
      This paper compares the quality of full-line grocery store information from Yelp,
      a crowdsourced content service, to a "ground truth" data set (Detroit Food Map)
      and a commercially-available dataset (Reference USA) for the greater Detroit
      area. Results suggest that Yelp is more accurate than Reference USA in
      identifying healthy food stores in urban areas. Researchers investigating the
      relationship between the nutrition environment and health may consider Yelp as a
      reliable and valid source for identifying sources of healthy food in urban
      environments.

PMID- 28455607
TI  - Effect of spineless cactus intake (Opuntia ficus-indica) on blood glucose levels
      in lactating sows and its impact on feed intake, body weight loss, and weaning
      estrus interval.
AB  - The effect of spineless cactus intake (Opuntia ficus-indica) on blood glucose
      (BG) levels in lactating sows and its impact on daily and total feed intake (dFI
      1 and TFI, respectively), body weight loss (BWL), and weaning-estrus interval
      length (WEI) were evaluated. Thirty-four hybrid (Yorkshire * Landrace * Pietrain)
      sows in lactation phase were used. Sows were divided into two groups: G1 (n = 17)
      where they received commercial feed and G2 (n = 17) provided with commercial feed
      plus an average of 2.0 +/- 0.5 kg spineless cactus, based on a sow's body weight.
      The variables evaluated were BG, dFI-1, TFI, BWL, and WEI. Statistical analysis
      was performed by using a fixed and mixed model methodology, under a repeated
      measurements experiment. Group effects were found on all analyzed variables (P <
      0.05). The BG was lower in G2 (55.2 and 64.5 mg/dL pre- and post-prandial,
      respectively), compared to that in G1 (70.9 and 80.1 mg/dL pre- and post
      prandial, respectively) (P < 0.05). G2 showed better performance than G1 for dFI
      1, BWL, and WEI (P < 0.05) whose averages were 5.5 +/- 1.8 kg, 7.4 +/- 4.5%, and
      5.3 +/- 1.2 days, respectively. Averages for these variables in G1 were 4.7 +/-
      1.5 kg, 16.8 +/- 4.6%, and 6.1 +/- 1.6 days, respectively. Intake of spineless
      cactus reduced BG levels in lactating sows, generating greater dFI-1, lower BWL
      at the end of lactation, and a lower WEI.

PMID- 28455609
TI  - Erratum to: Measurement of Macrophage-Specific In Vivo Reverse Cholesterol
      Transport in Mice.

PMID- 28455608
TI  - Expansion of CD11b+Ly6Ghigh and CD11b+CD49d+ myeloid cells with suppressive
      potential in mice with chronic inflammation and light-at-night-induced circadian
      disruption.
AB  - OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) are important negative
      regulators of immune processes in cancer and other pathological conditions. We
      suggested that MDSCs play a key role in pathogenesis of chronic inflammation,
      which precedes and, to a certain extent, induces carcinogenesis. The present
      study aimed at investigation of MDSCs arising during chronic inflammation and
      light-at-night (LN)-induced stress, which is shown to accelerate chronic
      diseases. SUBJECTS: 67 CD-1 mice and in vitro MDSC cultures. TREATMENT: Adjuvant
      arthritis was induced by a subdermal injection of complete Freund's adjuvant. LN
      was induced by illumination of 750 lx at night. METHODS: Flow cytometry for
      evaluation of cell phenotypes and MTT standard test for cell proliferation were
      used. RESULTS: Increased levels of splenic CD11b+Ly6Ghigh and CD11b+CD49d+
      myeloid cells possessing suppressive potential in mice with adjuvant arthritis
      are shown. LN amplifies the process of CD11b+Ly6Ghigh expansion in mice with
      adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid
      cells during exposure to LN. CONCLUSIONS: Our study raises the possibility that
      CD11b+Ly6Ghigh and CD11b+CD49d+ MDSCs play an important role in the induction of
      immunosuppressive environment typical for chronic inflammation. Also, LN can
      affect immune responses during chronic inflammation through recruitment of MDSCs
      from the bone marrow.

PMID- 28455610
TI  - Inhibition of Late Sodium Current as an Innovative Antiarrhythmic Strategy.
AB  - PURPOSE OF REVIEW: Over the last years, evidence is accumulating that enhanced
      late sodium current (INaL) in cardiac pathologies has fundamental consequences
      for cellular electrophysiology. This review discusses the underlying mechanisms
      of INaL-induced arrhythmias and the significance of INaL-inhibition as a possible
      therapeutic approach. RECENT FINDINGS: Inhibition of enhanced INaL, e.g., by
      ranolazine, was shown to reverse these effects in different myocardial diseases
      including heart failure. The antianginal drug ranolazine has already been
      examined in larger clinical trials with promising antiarrhythmic actions.
      Enhanced INaL was found to be present in several cardiac pathologies like
      ischemia, long QT syndromes, hypertrophic cardiomyopathy, and heart failure. In
      settings of enhanced INaL, a sodium-dependent calcium overload leads to severe
      impairment of excitation-contraction coupling and therefore has a high
      proarrhythmogenic potential. Experimental data showed that inhibition of INaL has
      a high antiarrhythmic potential which could be confirmed in further clinical
      trials.

PMID- 28455611
TI  - Evaluation of Virus Reduction by Ultrafiltration with Coagulation-Sedimentation
      in Water Reclamation.
AB  - The evaluation of virus reduction in water reclamation processes is essential for
      proper assessment and management of the risk of infection by enteric viruses.
      Ultrafiltration (UF) with coagulation-sedimentation (CS) is potentially effective
      for efficient virus removal. However, its performance at removing indigenous
      viruses has not been evaluated. In this study, we evaluated the reduction of
      indigenous viruses by UF with and without CS in a pilot-scale water reclamation
      plant in Okinawa, Japan, by measuring the concentration of viruses using the real
      time polymerase chain reaction (qPCR). Aichi virus (AiV) and pepper mild mottle
      virus (PMMoV) were targeted in addition to the main enteric viruses of concern
      for risk management, namely, norovirus (NoV) genogroups I and II (GI and GII) and
      rotavirus (RoV). PMMoV, which is a plant pathogenic virus and is present at high
      concentrations in water contaminated by human feces, has been suggested as a
      useful viral indicator. We also investigated the reduction of a spiked model
      virus (F-specific RNA bacteriophage MS2) to measure the effect of viral
      inactivation by both qPCR and plaque assay. Efficiencies of removal of NoV GI,
      NoV GII, RoV, and AiV by UF with and without CS were >0.5 to 3.7 log10, although
      concentrations were below the detection limit in permeate water. PMMoV was the
      most prevalent virus in both feed and permeate water following UF, but CS
      pretreatment could not significantly improve its removal efficiency (mean removal
      efficiency: UF, 3.1 log10; CS + UF, 3.4 log10; t test, P > 0.05). CS increased
      the mean removal efficiency of spiked MS2 by only 0.3 log10 by qPCR (t-test, P >
      0.05), but by 2.8 log10 by plaque assay (t-test, P < 0.01). This difference
      indicates that the virus was inactivated during CS + UF. Our results suggest that
      PMMoV could be used as an indicator of removal efficiency in water reclamation
      processes, but cultural assay is essential to understanding viral fate.

PMID- 28455612
TI  - Hsp90 inhibitors radicicol and geldanamycin have opposing effects on Leishmania
      Aha1-dependent proliferation.
AB  - Hsp90 and its co-chaperones are essential for the medically important parasite
      Leishmania donovani, facilitating life cycle control and intracellular survival.
      Activity of Hsp90 is regulated by co-chaperones of the Aha1 and P23 families. In
      this paper, we studied the expression of L. donovani Aha1 in two life cycle
      stages, its interaction with Hsp90 and the phenotype of Aha1 null mutants during
      the insect stage and inside infected macrophages. This study provides a detailed
      in vitro analysis of the function of Aha1 in Leishmania parasites and the first
      instance of a reverse genetic analysis of Aha1 in a protozoan parasite. While
      Aha1 is non-essential under standard growth conditions and at elevated
      temperature, Aha1 protects against ethanol stress. However, both overexpression
      and lack of Aha1 affected parasite growth in the presence of the Hsp90 inhibitors
      radicicol (RAD) and geldanamycin (GA). Under RAD pressure, P23 and Aha1 act in an
      antagonistic way. By contrast, expression levels of both co-chaperones have
      similar effects under GA treatment, indicating different inhibition mechanisms by
      the two compounds. Aha1 is also secreted in virulence-enhancing exosomes. This
      may explain why the loss of Aha1 reduces the infectivity of L. donovani in ex
      vivo mouse macrophages, indicating a role during the intracellular mammalian
      stage.

PMID- 28455613
TI  - Polymyxin B inhibits the chaperone activity of Plasmodium falciparum Hsp70.
AB  - Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important
      role in cellular proteostasis. Hsp70s are also implicated in the survival and
      pathogenicity of malaria parasites. The main agent of malaria, Plasmodium
      falciparum, expresses six Hsp70s. Of these, two (PfHsp70-1 and PfHsp70-z)
      localize to the parasite cytosol. Previously conducted gene knockout studies
      suggested that PfHsp70-z is essential, and it has been demonstrated that small
      molecule inhibitors targeting PfHsp70-1 cause parasite death. For this reason,
      both PfHsp70-1 and PfHsp70-z are potential antimalarial targets. Two cyclic
      lipopeptides, colistin and polymyxin B (PMB), have been shown to bind another
      heat shock protein, Hsp90, inhibiting its chaperone function. In the current
      study, we investigated the effect of PMB on the structure-function features of
      PfHsp70-1 and PfHsp70-z. Using surface plasmon resonance analysis, we observed
      that PMB directly interacts with both PfHsp70-1 and PfHsp70-z. In addition, using
      circular dichroism spectrometric analysis combined with tryptophan fluorescence
      measurements, we observed that PMB modulated the secondary and tertiary
      structures of Hsp70. Furthermore, PMB inhibited the basal ATPase activity and
      chaperone function of the two Hsp70s. Our findings suggest that PMB associates
      with Hsp70 to inhibit its function. In light of the central role of Hsp70 in
      cellular proteostasis and its essential role in the development of malaria
      parasites in particular, our findings expand the library of small-molecule
      inhibitors that target this medically important class of molecular chaperones.

PMID- 28455614
TI  - [Importance of investigation of fetal eyes : Supplement to fetal autopsy].
AB  - The investigation of fetal eyes is a subspecialty, which is performed by only a
      few ophthalmic pathologists and pathologists in specialized centers. If a certain
      fetal syndrome is suspected, the fetal eyes should be removed and submitted for
      ophthalmic pathological investigation in a specialized center. This can provide
      additional diagnostic information allowing a final classification of a syndrome
      and the comprehensive genetic counselling of parents with respect to future
      pregnancies. This article provides an overview of the histopathological findings
      in fetal eyes, which are of particular relevance for the pediatric pathological
      autopsy. In addition, the basic points of ocular development, the preparation of
      fetal eyes and frequent artifacts are presented.

PMID- 28455615
TI  - Enhancement of antibiotic productions by engineered nitrate utilization in
      actinomycetes.
AB  - Nitrate is necessary for primary and secondary metabolism of actinomycetes and
      stimulates the production of a few antibiotics, such as lincomycin and rifamycin.
      However, the mechanism of this nitrate-stimulating effect was not fully
      understood. Two putative ABC-type nitrate transporters were identified in
      Streptomyces lincolnensis NRRL2936 and verified to be involved in lincomycin
      biosynthesis. With nitrate supplementation, the transcription of nitrogen
      assimilation genes, nitrate-specific ABC1 transporter genes, and lincomycin
      exporter gene lmrA was found to be enhanced and positively regulated by the
      global regulator GlnR, whose expression was also improved. Moreover, heterologous
      expression of ABC2 transporter genes in Streptomyces coelicolor M145 resulted in
      an increased actinorhodin production. Further incorporation of a nitrite-specific
      transporter gene nirC, as in nirC-ABC2 cassette, led to an even higher
      actinorhodin production. Similarly, the titers of salinomycin, ansamitocin,
      lincomycin, and geldanamycin were increased with the integration of this cassette
      to Streptomyces albus BK3-25, Actinosynnema pretiosum ATCC31280, S. lincolnensis
      LC-G, and Streptomyces hygroscopicus XM201, respectively. Our work expanded the
      nitrate-stimulating effect to many antibiotic producers by utilizing the nirC
      ABC2 cassette for enhanced nitrate utilization, which could become a general tool
      for titer increase of antibiotics in actinomycetes.

PMID- 28455616
TI  - Development and application of anticancer fluorescent CdS nanoparticles enriched
      Lactobacillus bacteria as therapeutic microbots for human breast carcinoma.
AB  - Applications of probiotic bacteria and nanoparticles (NPs) as therapeutic agents
      have great importance. This study demonstrates a combinatorial approach of both
      the probiotic Lactobacillus spp. (Lactobacillus fermentum and Lactobacillus
      plantarum) with fluorescent cadmium sulfide (CdS) NPs as therapeutic agents to
      target MCF-7 cancer cells (human breast cancer cells). In this study, facultative
      anaerobic Lactobacillus was successfully used as a vehicle to transport NPs into
      MCF-7 cancer cells. The cell viability assay and invasion study along with
      confocal and field emission scanning electron microscopy (FESEM) confirmed the
      release of payload (CdS NPs) into cytoplasm without any external stimuli. The
      biosynthesized CdS NPs of ~22 nm were characterized by FESEM, transmission
      electron microscopy (TEM), atomic force microscopy (AFM), and fluorescence
      spectroscopy. The bacteria-NPs (microbots) interaction was investigated by growth
      curve studies, attenuated total reflection Fourier transform infrared
      spectroscopy (ATR-FTIR), FESEM, energy dispersive X-ray spectroscopy (EDX), and
      fluorescence and confocal microscopy. This alternative approach showed an
      approved and inexpensive delivering mode of specific functional cargos or
      therapeutic agents into the cancer cells.

PMID- 28455617
TI  - Progressive response of large intestinal bacterial community and fermentation to
      the stepwise decrease of dietary crude protein level in growing pigs.
AB  - The study aimed to determine the effects of reduction of dietary crude protein
      (CP) level with balanced essential amino acids (EAA) on intestinal bacteria and
      their metabolites of growing pigs. Forty pigs (initial BW 13.50 +/- 0.50 kg, 45
      +/- 2 days of age) were randomly assigned to four dietary treatments containing
      CP levels at 20.00% (normal crude protein, NP); 17.16% (medium crude protein,
      MP); 15.30% (low crude protein, LP); and 13.90% (extremely low crude protein,
      ELP), respectively. Crystalline AAs were added to meet the EAA requirement of
      pigs. After 4-week feeding, eight pigs per treatment (n = 8) were randomly
      selected and slaughtered for sampling of ileal, cecal, and colonic digesta and
      mucosa. Pigs with moderately reduced CP level had increased bacterial diversity,
      with the Shannon diversity indices for the colon digesta in the LP group and
      mucosa in the MP and LP groups significantly (P < 0.05) higher than those in the
      NP and ELP groups. As the CP level reduces, the Bifidobacterium population were
      linearly decreased (P < 0.05) both in ileum, cecum, and colon, and the ELP group
      had the lowest Bifidobacterium population in the cecum and colon, with its value
      significantly lower than NP and MP groups (P < 0.05). However, the ELP group had
      the highest population of Escherichia coli in the colon, with its value
      significantly higher than the LP group (P < 0.05). For bacterial metabolites, as
      CP level decreased, total short-chain fatty acid (T-SCFA), acetate, and butyrate
      were linearly increased (linear, P < 0.05) in the ileum, while all SCFAs except
      formate in the cecum and T-SCFA and acetate in the colon, were linearly decreased
      (P < 0.05). Reducing CP level led to a linear decrease of microbial crude protein
      (MCP) in the ileum (P < 0.05) and ammonia in all intestine segments (P < 0.05).
      The spermidine in cecum and total amines, cadaverine, methylamine, and spermidine
      in colon were shown a quadratic change (P < 0.05) as dietary CP decreases, with
      the highest concentration in LP group. These findings suggest that moderate
      reduction of dietary CP level may benefit large intestinal bacterial community
      and its fermentation, which was negatively affected by extremely low CP diet.

PMID- 28455619
TI  - Reply to Trends in Education-Specific Life Expectancy, Data Quality, and Shifting
      Education Distributions: A Note on Recent Research.

PMID- 28455618
TI  - [Imaging techniques in modern trauma diagnostics].
AB  - Modern trauma room management requires interdisciplinary teamwork and synchronous
      communication between a team of anaesthesists, surgeons and radiologists. As the
      length of stay in the trauma room influences morbidity and mortality of a
      severely injured person, optimizing time is one of the main targets. With the
      direct involvement of modern imaging techniques the injuries caused by trauma
      should be detected within a very short period of time in order to enable a
      priority-orientated treatment. Radiology influences structure and process
      quality, management and development of trauma room algorithms regarding the use
      of imaging techniques. For the individual case interventional therapy methods can
      be added. Based on current data and on the Frankfurt experience the current
      diagnostic concepts of trauma diagnostics are presented.

PMID- 28455620
TI  - Trends in Economic Homogamy: Changes in Assortative Mating or the Division of
      Labor in Marriage?
AB  - The growing economic resemblance of spouses has contributed to rising inequality
      by increasing the number of couples in which there are two high- or two low
      earning partners. The dominant explanation for this trend is increased
      assortative mating. Previous research has primarily relied on cross-sectional
      data and thus has been unable to disentangle changes in assortative mating from
      changes in the division of spouses' paid labor-a potentially key mechanism given
      the dramatic rise in wives' labor supply. We use data from the Panel Study of
      Income Dynamics (PSID) to decompose the increase in the correlation between
      spouses' earnings and its contribution to inequality between 1970 and 2013 into
      parts due to (a) changes in assortative mating, and (b) changes in the division
      of paid labor. Contrary to what has often been assumed, the rise of economic
      homogamy and its contribution to inequality is largely attributable to changes in
      the division of paid labor rather than changes in sorting on earnings or earnings
      potential. Our findings indicate that the rise of economic homogamy cannot be
      explained by hypotheses centered on meeting and matching opportunities, and they
      show where in this process inequality is generated and where it is not.

PMID- 28455621
TI  - Characteristics of advanced gastric cancer with negative or only perigastric
      lymph node metastasis in elderly patients.
AB  - OBJECTIVES: After gastrectomy with extended lymph node (LN) dissection, the
      damage of celiac plexus seems to cause of disorder of eating habits. To clarify
      the indication of gastrectomy with limited LN dissection for elderly patients,
      the pathological characteristics of advanced gastric cancer in elderly patients
      were examined in this study. METHODS: Forty-seven patients aged >=80 years with
      advanced gastric cancer (deeper than pT2) who underwent curative gastrectomy from
      1998 to 2015 were enrolled. Patients were classified into two groups by extent of
      LN metastasis: Group A, with N0 or only perigastric LN metastasis (n = 33); Group
      B, LN metastasis beyond the perigastric area (n = 14). Pathological factors were
      then evaluated. RESULTS: No significant differences were observed in age, sex,
      body mass index, American Society of Anesthesiologists physical status
      classification, serum level of carcinoembryonic antigen, surgical procedure,
      extent of LN dissection, and number of dissected LNs. Pathological findings
      showed no significant differences in tumor location, macroscopic type, histologic
      type, and lymphovascular invasion. However, significant differences were observed
      in tumor maximum diameter at the cut-off level of 40 mm (Group A: <=40 mm, n = 10
      and >40 mm, n = 23; Group B: <=40 mm, n = 0 and >40 mm, n = 14; P = 0.02).
      CONCLUSION: In the elderly patients, LN metastasis in advanced gastric cancer of
      <=40 mm in diameter was limited to be within the perigastric area. Gastrectomy
      with only perigastric LN dissection may be adopted in these patients.

PMID- 28455622
TI  - Focal nodular hyperplasia that mimicked a liver metastasis from a soft tissue
      sarcoma: a case report.
AB  - BACKGROUND: Imaging modalities (computed tomography (CT), ultrasonography, and
      magnetic resonance imaging (MRI)) have only limited ability to distinguish liver
      focal nodular hyperplasia (FNH) from metastatic liver tumors. Here, we report a
      patient who underwent surgery for benign FNH that mimicked a liver metastasis
      from soft tissue sarcoma (STS). CASE PRESENTATION: A 23-year-old man with a
      history of several surgeries for metastatic abdominal STS, developed a hepatic
      tumor accompanying peritoneal STS recurrence. He was diagnosed with a metastatic
      liver tumor from the STS, based on imaging studies for the hepatic tumor that
      showed a growing hypervascular lesion and hypo-intensity in hepatic phase on
      dynamic CT and MRI. However, when the liver and peritoneal tumors were resected,
      histological diagnosis showed the hepatic tumor to be benign liver FNH.
      CONCLUSIONS: Although FNH should be considered as a differential diagnosis for
      hypervascular hepatic tumors, it has few typical findings, and its appropriate
      management is controversial. A lesion strongly suspected of being a metastatic
      liver tumor might require surgical resection.

PMID- 28455623
TI  - Classification of normal sagittal spine alignment: refounding the Roussouly
      classification.
AB  - PURPOSE: Although the Roussouly classification of common variants in spinal
      sagittal alignment is well accepted, no studies have implemented it in an
      asymptomatic adult population. In addition, no study investigated the
      radiographic features of asymptomatic patients with an anteverted pelvis. The aim
      of this prospective radiographic study of 296 asymptomatic adults without spinal
      pathology was to investigate how the Roussouly classification could include the
      anteverted pelvis concept. METHODS: Pelvic incidence (PI), sacral slope (SS),
      pelvic tilt (PT), and the lumbar parameters lumbar lordosis (Global LL), lordosis
      tilt angle (LTA), total number of lordotic vertebra (LL verteb), and C7
      plumbline/sacrofemoral distance ratio (C7PL ratio) were evaluated in 296 healthy
      volunteers (126 males, 170 females; mean age, 27 years; range 18-48 years).
      Comparison between the five types of the Roussouly classification used Student,
      ANOVA, and Tukey tests for quantitative variables and chi 2, Fischer, and Holm
      tests for qualitative variables. RESULTS: Mean PI and PT were, respectively, (39
      degrees , 10 degrees ) for type 1, (41 degrees , 10 degrees ) for type 2, (53
      degrees , 13 degrees ) for type 3, and (62 degrees , 12 degrees ) for type 4 (p <
      0.0001 and p < 0.01). A sizable portion (16%) of the population (type 3 AP)
      showed low-grade PI (mean, 48 degrees  +/- 6 degrees ) despite having SS > 35
      degrees . PT was low or negative (mean 4 degrees  +/- 3 degrees ). C7PL ratio was
      >1 (in front of the hip axis) in 13% of all cases, and between 0 and 1 (between
      sacrum and hip axis) in 49%. CONCLUSION: Although asymptomatic adults stood with
      stable global balance, the sagittal spinal alignment of healthy subjects, newly
      divided in 5 sagittal types, varied significantly. Type 3 AP appears as a new and
      unusual sagittal shape with low-grade PI, very low or negative PT, and
      hyperlordosis. Whereas most asymptomatic adults stood with C7PL behind the hip
      axis, a sizeable portion had C7 in front of the hip axis. This could be a new
      controversial aspect of ideal spinal balance.

PMID- 28455624
TI  - [Time interval between neoadjuvant radiochemotherapy and resection in rectal
      cancer].

PMID- 28455625
TI  - Toward a consensus on SNP and STR mutation rates on the human Y-chromosome.
AB  - The mutation rate on the Y-chromosome matters for estimating the time-to-the-most
      recent-common-ancestor (TMRCA, i.e. haplogroup age) in population genetics, as
      well as for forensic, medical, and genealogical studies. Large-scale sequencing
      efforts have produced several independent estimates of Y-SNP mutation rates.
      Genealogical, or pedigree, rates tend to be slightly faster than evolutionary
      rates obtained from ancient DNA or calibrations using dated (pre)historical
      events. It is, therefore, suggested to report TMRCAs using an envelope defined by
      the average aDNA-based rate and the average pedigree-based rate. The current
      estimate of the "envelope rate" is 0.75-0.89 substitutions per billion base pairs
      per year. The available Y-SNP mutation rates can be applied to high-coverage data
      from the entire X-degenerate region, but other datasets may demand recalibrated
      rates. While a consensus on Y-SNP rates is approaching, the debate on Y-STR rates
      has continued for two decades, because multiple genealogical rates were
      consistent with each other but three times faster than the single evolutionary
      estimate. Applying Y-SNP and Y-STR rates to the same haplogroups recently helped
      to clarify the issue. Genealogical and evolutionary STR rates typically provide
      lower and upper bounds of the "true" (SNP-based) age. The genealogical rate often
      but not always-works well for haplogroups less than 7000 years old. The
      evolutionary rate, although calibrated using recent events, inflates ages of
      young haplogroups and deflates the age of the entire Y-chromosomal tree, but
      often provides reasonable estimates for intermediate ages (old haplogroups).
      Future rate estimates and accumulating case studies should further clarify the Y
      SNP rates.

PMID- 28455626
TI  - Influences of flavones on cell viability and cAMP-dependent steroidogenic gene
      regulation in MA-10 Leydig cells.
AB  - Testicular Leydig cells are major contributors of androgen synthesis and
      secretion, which play an important role in testis development, normal
      masculinization, maintenance of spermatogenesis, and general male fertility. The
      rate-limiting step in testosterone biosynthesis involves the transfer of
      cholesterol to the mitochondrial inner membrane by the steroidogenic acute
      regulatory (Star) protein, a critical factor in steroid hormone biosynthesis.
      Once inside the mitochondria, cholesterol is metabolized by the steroidogenic
      enzyme Cyp11a1 to pregnenolone, which is further converted to testosterone by the
      action of other steroidogenic enzymes. Interestingly, the Star protein level
      declines during Leydig cell aging, resulting in defective mitochondrial
      cholesterol transfer and lower testosterone production. It is possible to delay
      the age-related decline in testosterone production by increasing Star and/or
      Cyp11a1 gene expression using supplementation with flavonoids, a group of
      polyphenolic compounds widely distributed in fruits and vegetables. In this
      study, we examined whether the distribution of hydroxyl groups among flavones
      could influence their potency to stimulate steroidogenesis within Leydig cells.
      Low levels of apigenin, luteolin, chrysin, and baicalein (10 MUM) stimulated cAMP
      dependent Star, Cyp11a1, and Fdx1 promoters' activation and may increase
      steroidogenesis within Leydig cells. Indeed, luteolin effectively increased cAMP
      dependent accumulation of progesterone from MA-10 Leydig cells, possibly through
      activation of Star and Fdx1 transcription. Thus, dietary luteolin could be
      potentially effective to maintain steroid production within aging males.

PMID- 28455627
TI  - Immunization with recombinant schistosome adenylate kinase 1 partially protects
      mice against Schistosoma japonicum infection.
AB  - Highly effective and safe prophylactic vaccines are urgently needed to
      sustainably control schistosomiasis, one of the most serious endemic zoonoses in
      China. In this study, we characterized adenylate kinase 1 from Schistosoma
      japonicum (SjAK1), a phosphotransferase that regulates cellular energy and
      metabolism, and evaluated its potential as a recombinant vaccine. Based on real
      time quantitative PCR, western blot, and immunolocalization, SjAK1 is active
      throughout the life of the worm, although its expression is higher in 21-day-old
      schistosomula, adult worms, and eggs deposited in the host liver. Further, the
      enzyme accumulates in the eggshell, intestinal epithelium, integument of adult
      worms and in the vitellaria tissue in female worms. A 594-bp full-length
      complementary DNA (cDNA) encoding SjAK1 was synthesized from total RNA of 3-day
      old schistosomes, and immunization with recombinant SjAK1 reduced worm burden by
      50%, decreased the density of eggs deposited in the host liver by 40%, and
      reduced the area of granulomas in the host liver by 56%. ELISA results showed
      that recombinant SjAK1 also stimulated Th1 cytokines such as IL-2 and IFN-gamma,
      but not IL-5 and IL-4. Collectively, a recombinant form of the enzyme SjAK1
      elicits partial protective immunity against Schistosoma japonicum infection and
      the induction of Th1 cytokines. Thus, the enzyme has potential as a component of
      a multivalent vaccine against schistosomiasis.

PMID- 28455628
TI  - Identification of antigenic proteins in Strongyloides stercoralis by proteomic
      analysis.
AB  - Strongyloides stercoralis is an intestinal helminth that infects people
      worldwide. Hyperinfection or disseminated human strongyloidiasis can involve
      vital organs, leading to lethal outcomes. We analyzed immunoproteomics of
      antigenic spots, derived from S. stercoralis third-stage larvae and reacted with
      human strongyloidiasis sera, by two-dimensional gel electrophoresis and
      immunoblotting. Of 26 excised antigenic spots analyzed by liquid chromatography
      electrospray ionization-tandem mass spectrometry, 20 proteins were identified.
      Most proteins were associated with enzymes involved in the metabolic process,
      energy generation, and oxidation-reduction. The proteins relate to promotion of
      worm development, cell division, cell signaling and transportation, and
      regulation of muscular contraction. Identification of antigenic proteins shows
      promise in helping to discover potential diagnostic protein markers or vaccine
      candidates for S. stercoralis infection.

PMID- 28455629
TI  - Validation of an active shape model-based semi-automated segmentation algorithm
      for the analysis of thigh muscle and adipose tissue cross-sectional areas.
AB  - OBJECTIVE: To validate a semi-automated method for thigh muscle and adipose
      tissue cross-sectional area (CSA) segmentation from MRI. MATERIALS AND METHODS:
      An active shape model (ASM) was trained using 113 MRI CSAs from the
      Osteoarthritis Initiative (OAI) and combined with an active contour model and
      thresholding-based post-processing steps. This method was applied to 20 other
      MRIs from the OAI and to baseline and follow-up MRIs from a 12-week lower-limb
      strengthening or endurance training intervention (n = 35 females). The agreement
      of semi-automated vs. previous manual segmentation was assessed using the Dice
      similarity coefficient and Bland-Altman analyses. Longitudinal changes observed
      in the training intervention were compared between semi-automated and manual
      segmentations. RESULTS: High agreement was observed between manual and semi
      automated segmentations for subcutaneous fat, quadriceps and hamstring CSAs. With
      strength training, both the semi-automated and manual segmentation method
      detected a significant reduction in adipose tissue CSA and a significant gain in
      quadriceps, hamstring and adductor CSAs. With endurance training, a significant
      reduction in adipose tissue CSAs was observed with both methods. CONCLUSION: The
      semi-automated approach showed high agreement with manual segmentation of thigh
      muscle and adipose tissue CSAs and showed longitudinal training effects similar
      to that observed using manual segmentation.

PMID- 28455630
TI  - Relationship between carotid plaque surface morphology and perfusion: a 3D DCE
      MRI study.
AB  - OBJECTIVE: This study aims to explore the relationship between plaque surface
      morphology and neovascularization using a high temporal and spatial resolution 4D
      contrast-enhanced MRI/MRA sequence. MATERIALS AND METHODS: Twenty one patients
      with either recent symptoms or a carotid artery stenosis >=40% were recruited in
      this study. Plaque surface morphology and luminal stenosis were determined from
      the arterial phase MRA images. Carotid neovascularization was evaluated by a
      previously validated pharmacokinetic (PK) modeling approach. K trans (transfer
      constant) and v p (partial plasma volume) were calculated in both the adventitia
      and plaque. RESULTS: Image acquisition and analysis was successfully performed in
      28 arteries. Mean luminal stenosis was 44% (range 11-82%). Both adventitial and
      plaque K trans in ulcerated/irregular plaques were significantly higher than
      smooth plaques (0.079 +/- 0.018 vs. 0.064 +/- 0.011 min-1, p = 0.02; 0.065 +/-
      0.013 vs. 0.055 +/- 0.010 min-1, p = 0.03, respectively). Positive correlations
      between adventitial K trans and v p against stenosis were observed (r = 0.44, p =
      0.02; r = 0.55, p = 0.01, respectively). CONCLUSION: This study demonstrates the
      feasibility of using a single sequence to acquire both high resolution 4D CE-MRA
      and DCE-MRI to evaluate both plaque surface morphology and function. The results
      demonstrate significant relationships between lumen surface morphology and
      neovascularization.

PMID- 28455631
TI  - Real-time three dimensional CT and MRI to guide interventions for congenital
      heart disease and acquired pulmonary vein stenosis.
AB  - To validate the feasibility and spatial accuracy of pre-procedural 3D images to
      3D rotational fluoroscopy registration to guide interventional procedures in
      patients with congenital heart disease and acquired pulmonary vein stenosis.
      Cardiac interventions in patients with congenital and structural heart disease
      require complex catheter manipulation. Current technology allows registration of
      the anatomy obtained from 3D CT and/or MRI to be overlaid onto fluoroscopy.
      Thirty patients scheduled for interventional procedures from 12/2012 to 8/2015
      were prospectively recruited. A C-arm CT using a biplane C-arm system (Artis zee,
      VC14H, Siemens Healthcare) was acquired to enable 3D3D registration with pre
      procedural images. Following successful image fusion, the anatomic landmarks
      marked in pre-procedural images were overlaid on live fluoroscopy. The accuracy
      of image registration was determined by measuring the distance between overlay
      markers and a reference point in the image. The clinical utility of the
      registration was evaluated as either "High", "Medium" or "None". Seventeen
      patients with congenital heart disease and 13 with acquired pulmonary vein
      stenosis were enrolled. Accuracy and benefit of registration were not evaluated
      in two patients due to suboptimal images. The distance between the marker and the
      actual anatomical location was 0-2 mm in 18 (64%), 2-4 mm in 3 (11%) and >4 mm in
      7 (25%) patients. 3D3D registration was highly beneficial in 18 (64%),
      intermediate in 3 (11%), and not beneficial in 7 (25%) patients. 3D3D
      registration can facilitate complex congenital and structural interventions. It
      may reduce procedure time, radiation and contrast dose.

PMID- 28455632
TI  - Utility of stress perfusion-cardiac magnetic resonance in follow-up of patients
      undergoing percutaneous coronary interventions of the left main coronary artery.
AB  - To assess the accuracy of cardiac magnetic resonance (CMR) for the diagnosis of
      angiographic stenosis after percutaneous coronary intervention (PCI) of left main
      coronary artery (LMCA). Patients undergone in the last year PCI of unprotected
      LMCA and scheduled for conventional X-ray coronary angiography (CXA) were
      evaluated with stress perfusion CMR within 2 weeks before CXA. Main
      contraindications to CMR were exclusion criteria. Stress perfusion CMR was
      performed to follow a bolus of contrast Gadobutrol after 3 min of adenosine
      infusion. Between the 50 patients enrolled, only 1 did not finish the CMR
      protocol and 49 patients with median age 71 (65-75) years (38 male, 11 female)
      were analyzed. Between 784 coronary angiographic segments evaluated we found 75
      stenosis or occlusions (prevalence 9.5%), but only 13 stenosis or occlusions in
      proximal segments (prevalence 6.6%). Patients with coronary stenosis (n = 12,
      24%) showed a significantly (p = 0.002) higher prevalence of diabetes (7 of 12,
      58%). At CMR examination, late gadolinium enhancement was present in 25 (51%),
      reversible perfusion defects in 12 (24%), and fixed perfusion defects in 6
      subjects (12%). The only patient with LMCA restenosis resulted positive at
      perfusion CMR. The accuracy of stress perfusion CMR in diagnosis of coronary
      stenosis was higher when the analysis was performed only in proximal coronary
      arteries (95%, CI 86-99) compared to overall vessels (84%, CI 70-92). Stress
      perfusion CMR could strongly reduce the need for elective CXA in follow up of
      LMCA PCI and should be validated in further multicenter prospective studies.

PMID- 28455633
TI  - Evaluation of left ventricular myocardial mechanics by three-dimensional speckle
      tracking echocardiography in the patients with different graded coronary artery
      stenosis.
AB  - To investigate the relationship between left ventricular (LV) myocardial
      mechanics evaluated by three-dimensional speckle tracking echocardiography (3D
      STE) and degree of coronary artery stenosis in patients with coronary artery
      disease (CAD). Ninety-seven suspected CAD patients without LV regional wall
      motion abnormality (RWMA) observed visually form traditional echocardiography
      were divided into four groups according to coronary artery angiography (CAG): 23
      patients in slight stenosis group [stenosis rate (SR) <=25%], 26 patients in mild
      stenosis group (25< SR <=50%), 28 patients in moderate stenosis group (50< SR
      <=75%), and 20 patients in severe stenosis group (SR >75%). Global longitudinal
      strain (GLS), circumferential strain (GCS), radial strain (GRS), area strain (AS)
      and three dimensional strain (3D-Strain) were obtained. The parameters from 3D
      STE were compared between different groups and then the diagnostic value of
      global strains indicating different graded coronary artery stenosis was analyzed
      by the receiver operating characteristic curve. (1) There were significant
      difference in GLS, GCS, GRS, GAS and 3D-Strain between the severe stenosis group
      and any other group while all 3D-STE parameters except GCS in the moderate
      stenosis group were remarkably different from those respectively in mild group.
      (2) Receiver operator characteristic curve (ROC) analysis showed that the area
      under the curve of GLS, GRS, GCS, GAS, 3D-Strain were 0.899, 0.873, 0.723, 0.856
      and 0.863 respectively for the identification of stenosis rate >50%, and 0.896,
      0.866, 0.797, 0.909 and 0.899 respectively for the identification of severe
      stenosis. GAS less than -29.13% allowed a sensitivity of 95% and a specificity of
      71.4%, while 3D strain less than 41.35% allowed a sensitivity of 90% and a
      specificity of 80.5% for evaluating serve coronary artery stenosis. The
      myocardial mechanics from 3D-STE in the CAD patients were characteristic. It
      could be expected to identify serve coronary stenosis with a good sensitivity and
      an acceptable specificity by using GAS or 3D-strain especially in the suspected
      CAD patients without RWMA on conventional echocardiography.

PMID- 28455634
TI  - Depression of leukocyte protein synthesis, immune function and growth performance
      induced by high environmental temperature in broiler chickens.
AB  - In tropical and semitropical regions, raising broiler chickens out of their
      thermal comfort zone can cause an added economic loss in the poultry industry.
      The cause for the deleterious effects on immunity and growth performance of
      broilers under high environmental temperatures is still poorly understood.
      Therefore, the aim of the current investigation was to evaluate the effect of
      heat stress on leukocytes protein synthesis and immune function as a possible
      direct cause of low performance in broiler chickens under such condition. In this
      study, 300 one-day-old male broiler chicks (Cobb500TM) were randomly assigned
      into 2 groups with 5 replicates of 30 chicks each. From 21 to 42 days of age, one
      group was exposed to non-stressed condition at 24  degrees C and 50% relative
      humidity (control group), while the other group was exposed to heat stress at 35 
      degrees C and 50% relative humidity (HS group). At 42 days of age, blood samples
      were collected from each group to evaluate stress indicators, immune function,
      and leukocytes protein synthesis. Production performance was also recorded.
      Noteworthy, protein synthesis in leukocytes was significantly (P < 0.05)
      inhibited in HS group by 38% compared to control group. In contrast, the
      phosphorylation level on threonine 56 site (Thr56) of eukaryotic elongation
      factor (eEF2), which indicates the suppression of protein translation process
      through altering the protein elongation phase, was significantly threefold higher
      in HS group than in control (P < 0.05). In addition, an increase in stress
      indicators was markedly (P < 0.05) presented in the HS birds by twofold increase
      in heterophil/lymphocyte (H/L) ratio and threefold increase in plasma
      corticosterone level compared to control. Furthermore, the immune function was
      significantly (P < 0.05) suppressed in HS birds than control (0.99 vs. 1.88 mg/mL
      plasma IgG, 89.2 vs. 148.0 MUg/mL plasma IgM, 4.80 vs. 7.20 antibody titer
      against SRBC, and 1.38 vs. 3.39 stimulation index of lymphocyte proliferation in
      HS vs. control group, respectively). Moreover, results on the broiler performance
      indicate that HS birds had a significant (P < 0.05) lower body weight gain by
      58%, lower feed consumption by 39%, higher conversion ratio by 27%, and higher
      mortality by more than three times, compared to control birds. In conclusion, our
      results demonstrate that the inhibition of leukocyte protein synthesis through
      increasing the level of eEF2 Thr56 phosphorylation may play a key role in the
      observed decrease in immune function and growth performance with the high
      mortality rate encountered in broiler chickens under heat stress environment.

PMID- 28455635
TI  - Seasonality in hospital admissions of Crimean-Congo hemorrhagic fever and its
      dependence on ambient temperature-empirical evidence from Pakistan.
AB  - Crimean-Congo hemorrhagic fever (CCHF) has been reported from all provinces of
      Pakistan. Little is known about the seasonal variations in the disease and its
      association with weather conditions. In this study, we explored time-series data
      about monthly number of CCHF admissions (2007-2010) in three public sector
      hospitals of Quetta-the capital city of Baluchistan province of Pakistan. Cosinor
      analysis was carried out to investigate seasonality in the data. To assess the
      effect of average monthly ambient temperature ( degrees C) on disease, a
      distributed lag nonlinear model (DLNM) was applied. Cosinor model revealed
      statistically significant seasonality in monthly number of CCHF patients admitted
      to the study hospitals. The estimated amplitude was 3.24 cases per month with
      phase in mid-June and low point in mid-December. DLNM confirmed nonlinear and
      delayed effect of temperature on hospital admissions. At a lag of 2 months, the
      cumulative relative risk was more than 1 at temperature at 18.37  degrees C and
      above. In addition, relative risk was significantly high at 60th (21.98  degrees
      C), 70th (24.50  degrees C), 80th (27.33  degrees C), and 90th (29.25  degrees C)
      percentiles of temperature (relative to median value, 18.37  degrees C).
      Inclusion of Eid-al-Adha as a predictor did not improve the fitness of DLNM.
      Based on our analysis, we concluded significant seasonality in CCHF hospital
      admissions. Our findings also suggested average monthly ambient temperature (
      degrees C) as a significant predictor of CCHF hospitalizations. DLNM presented in
      this study may be improved with inclusion of other possible time-varying
      predictors particularly meteorological conditions of this region.

PMID- 28455636
TI  - Childhood Neglect, Internalizing Symptoms and Adolescent Substance Use: Does the
      Neighborhood Context Matter?
AB  - Childhood neglect is associated with risk behaviors in adolescence, including
      substance use. There is evidence that internalizing behaviors may serve as a
      mechanism linking childhood neglect and substance use; however, further research
      is needed to examine this developmental pathway. According to developmental and
      ecological approaches, the neighborhood context and the developmental timing of
      maltreatment should both be considered when examining the sequelae of childhood
      neglect. Hence, the present study uses a longitudinal sample of youth (N = 965,
      49.1% female, 59.2% African-American) to examine the influence of timing in the
      relationship between childhood neglect and adolescent psychopathology, and to
      examine the indirect effects of child neglect on substance use via internalizing
      symptoms in adolescence. Furthermore, the role of neighborhood disorder in this
      indirect effect was tested. Five data collection time points were used: Time 1(M
      age  = 4.557, SD age  = .701), Time 2 (M age  = 6.422, SD age  = .518), Time 3 (M
      age  = 12.370, SD age  = .443), Time 4 (M age  = 14.359, SD age  = .452), and
      Time 5 (M age  = 16.316, SD age  = .615). The findings showed that internalizing
      problems mediated the link between the severity of neglect in early childhood and
      adolescent substance use, and this pathway was moderated by neighborhood
      disorder. These results have implications for preventative interventions aimed
      toward reducing substance use for at-risk adolescents.

PMID- 28455637
TI  - Optical and electronic structure description of metal-doped phthalocyanines.
AB  - Phthalocyanines represent a crucial class of organic compounds with high
      technological appeal. By doping the center of these systems with metals, one
      obtains the so-called metal-phthalocyanines, whose property of being an effective
      electron donor allows for potentially interesting uses in organic electronics. In
      this sense, investigating optical and electronic structure changes in the
      phthalocyanine profiles in the presence of different metals is of fundamental
      importance for evaluating the appropriateness of the resulting system as far as
      these uses are concerned. In the present work, we carry out this kind of effort
      for phthalocyanines doped with different metals, namely, copper, nickel, and
      magnesium. Density functional theory was applied to obtain the absorption
      spectra, and electronic and structural properties of the complexes. Our results
      suggest that depending on the dopant, a different level of change is achieved.
      Moreover, electrostatic potential energy mapping shows how the charge
      distribution can be affected by solar radiation. Our contribution is crucial in
      describing the best possible candidates for use in different organic photovoltaic
      applications. Graphical Abstract Representation of meta-phthalocyanine systems.
      All calculations of this work are based on varying metal position along z axis,
      considering the z-axis has its zero point matching with the center of
      phthalocyanine cavityconsidering.

PMID- 28455638
TI  - Radiologist Digital Workspace Use and Preference: a Survey-Based Study.
AB  - Literature regarding the heterogeneity of and preferences for radiology
      workstation design-and, in particular, the digital workspace of the radiology
      workstation-is scant. The purpose of this study was to determine the nature of
      the digital environments across the specialty and the degree of satisfaction
      users associated with the particular facets of those environments. A survey was
      sent to the membership of the Association of University Radiologists in February
      2015. The survey comprised 10 questions establishing demographics, current
      typical workstation setup, perceived satisfaction with that setup, and
      preferences for potential altered setups. A total of 336 radiologists responded,
      with a cross-section similar to that described in the 2015 ACR annual workforce
      survey (1). Although there was a rough split in the number of radiologists using
      one or two non-diagnostic monitors (46 vs. 51%, respectively), the strong
      majority (75%) of radiologists use two diagnostic monitors. Users of two non
      diagnostic monitors were more likely to keep open the case info (87 vs. 68%) and
      EMR (84 vs 68%). More senior radiologists tended to find the current setup easy
      more frequent than younger radiologists, and the latter group was more likely to
      believe additional monitors would be helpful. Although many radiologists are
      comfortable with their computing workflows, a significant number indicate
      dissatisfaction and may be interested in being able to specify the amount of
      monitor space with which they can work. Additional monitors may promote improved
      quality in addition to any potential productivity gains.

PMID- 28455639
TI  - The association between fear of cancer recurrence and quality of life among
      Chinese cancer survivors: main effect hypothesis and buffering hypothesis.
AB  - PURPOSE: The aim of the present study is to examine whether fear of cancer
      recurrence (FCR) is related to health-related quality of life (HRQOL) among
      Chinese cancer survivors, an understudied population (i.e., main effect
      hypothesis). Also, we investigated whether the FCR-HRQOL link is moderated by two
      coping strategies, avoidance and positive reappraisal (i.e., buffering
      hypothesis). METHODS: This is a cross-sectional study conducted among 238 Chinese
      cancer survivors in Beijing. Participants completed a set of questionnaires
      including FCR, coping, and HRQOL. RESULTS: FCR was related to lower physical,
      psychological, social, and spiritual well-beings, even when demographics, cancer
      related factors, and coping were taken into account. There was only one
      moderation effect between FCR and avoidance coping. Surprisingly, the detrimental
      effect of FCR on spiritual well-being was lessened among those with high
      avoidance coping such that the negative association between FCR and spiritual
      well-being was only found in those with low avoidance coping and not among those
      with high avoidance coping. CONCLUSIONS: Findings largely supported the main
      effect hypothesis. FCR was associated with diverse domains of HRQOL among Chinese
      cancer survivors. The buffering hypothesis was largely not supported in this
      population. Rather, in some cases, the effects of FCR and coping strategies on
      HRQOL were independent. Thus, ways to attenuate the harmful effects of FCR on
      HRQOL among Chinese cancer survivors remain unresolved. It is urgent and timely
      that future studies focus on FCR and HRQOL in this population.

PMID- 28455640
TI  - Enrollment in early head start and oral health-related quality of life.
AB  - PURPOSE: Dental problems in young children are widespread and can negatively
      impact quality of life. We examined the effect of enrollment in North Carolina
      Early Head Start (EHS)-a federally funded early education program for children
      under three years of age and their families-on oral health-related quality of
      life (OHRQoL). METHODS: In this quasi-experimental study, we interviewed 479 EHS
      and 699 Medicaid matched parent-child dyads at baseline (children's average age
      10 months) and 24 months later. Parents reported OHRQoL using the Early Childhood
      Oral Health Impact Scale (ECOHIS), a 0-52 point scale with higher scores
      representing more negative impacts. We used a marginalized semicontinuous two
      part model to estimate: (1) the effect of EHS on the probability of reporting any
      follow-up impacts (ECOHIS >= 1), and (2) the difference in overall mean ECOHIS
      follow-up scores. We controlled for baseline ECOHIS, language, and EHS and non
      EHS group imbalances using a propensity score. RESULTS: At follow-up, negative
      OHRQoL impacts were more often reported by parents of non-EHS than EHS children
      (45 versus 37%, P < .01). In the adjusted model, EHS parents reported a lower
      odds of negative OHRQoL impacts (OR 0.70; 95% CI 0.52, 0.94). Mean adjusted
      ECOHIS scores were not significantly different (EHS: 1.59 +/- 3.34 versus non
      EHS: 2.11 +/- 3.85, P > 0.05). CONCLUSIONS: This study is the first to
      demonstrate that families of young children enrolled in EHS report improved
      OHRQoL compared to their non-enrolled peers. These results highlight the
      potential effectiveness of improving the quality of life of low-resource families
      through early childhood education.

PMID- 28455641
TI  - Response of performance and bacterial community to oligotrophic stress in biofilm
      systems for raw water pretreatment.
AB  - Understanding the dynamics of performance and bacterial community of biofilm
      under oligotrophic stress is necessary for the process optimization and risk
      management in biofilm systems for raw water pretreatment. In this study, biofilm
      obtained from a pilot-scale biofilm reactor was inoculated into a pilot-scale
      experimental tank for the treatment of oligotrophic raw water. Results showed
      that the removal of NH4+-N was impaired in biofilm systems when influent NH4+-N
      was less than 0.35 mg L-1 or NH4+-N loading rate of less than 7.51 mg L-1 day-1.
      The dominant bacteria detected in biofilm of different carrier were obvious
      distinct from phylum to genus level under oligotrophic stress. The dominant
      bacteria in elastic stereo media carrier changed from Proteobacteria (51.1%) to
      Firmicutes (32.7%), while Proteobacteria was always dominant in suspended ball
      carrier after long-term operation under oligotrophic conditions. Oligotrophic
      stress largely decreased the functional bacteria for the removal of nitrogen and
      organics including many genera in Proteobacteria and Nitrospirae, but increased
      several genera with spore forming organisms or potential bacterial pathogens in
      ESM carrier mainly including Bacillus, Mycobacterium, Pseudomonas, etc.

PMID- 28455642
TI  - Double bubble with the big-bubble technique during deep anterior lamellar
      keratoplasty.
AB  - PURPOSE: To report a case of intraoperative double bubble that formed during big
      bubble DALK surgery in a patient with corneal scarring secondary to herpetic
      stromal keratitis. METHODS: Case report. RESULTS: A 22 year old woman presented
      with a large corneal scar, likely secondary to previous herpetic stromal
      keratitis. She underwent big-bubble DALK surgery for visual rehabilitation.
      Intraoperatively, a mixed bubble with persistent type 2 bubble postoperatively
      was noted. The second bubble resorbed with clearance of the graft and good visual
      outcome after 6 weeks. CONCLUSIONS: This case report describes the unusual
      development of a mixed bubble during big-bubble DALK surgery. This graft cleared
      with resolution of the second bubble postoperatively without further surgical
      intervention.

PMID- 28455643
TI  - Evaluating the Change in Medical Marijuana Dispensary Locations in Los Angeles
      Following the Passage of Local Legislation.
AB  - In May 2013, Los Angeles voters approved Proposition D, a regulatory measure that
      set zoning restrictions and capped the number of dispensaries at those that
      opened before 2007. Specifically, Proposition D stated that only 135 dispensaries
      were allowed to be in operation and set zoning restrictions prohibiting
      dispensaries from operating in certain areas. We first assessed whether the
      legislation changed the physical availability of medical marijuana via
      dispensaries in Los Angeles. We then used two data points 1 year prior to and 1
      year following the implementation of Proposition D to determine if the locations
      of where the dispensaries are located changed after the enactment of Proposition
      D. Using a cross-sectional, ecological design, we investigated the change in
      dispensaries from 2012 to 2014 for Census tracts within the city of Los Angeles
      (N = 1000). We analyzed data using spatial error regression models that included
      controls for spatial autocorrelation due to the spatial structure of the data. We
      found that while the total number of dispensaries in Los Angeles remained largely
      unchanged, the spatial distribution of dispensaries did change in meaningful
      ways. Census tracts with more dispensaries in 2014 were significantly and
      positively associated with the proportion of African American residents and
      negatively associated with the percent of area that was commercially zoned. In
      other words, dispensaries opened in areas with a higher proportion of Black
      residents and closed in Census tract areas that had a higher percentage of
      commercially zoned land. Findings from this study highlight the importance of
      continuously regulating dispensary locations. Results suggest that likely as a
      result of changing regulations, dispensaries may be attempting to conceal their
      presence and locate in areas that will not advocate against their presence.

PMID- 28455645
TI  - On Medicine and Boundaries: Frost's Mending Wall.
AB  - Published just over a century ago, Robert Frost's Mending Wall stands as one of
      the most eloquent meditations on boundaries and the complex and nuanced role they
      play in interpersonal relationships. Often anthologized, and perhaps as often
      misunderstood, Mending Wall has much to teach medical educators and practicing
      clinicians about the physician-patient relationship and the evolving dynamic
      between healer and patient. Remembered mostly for the seemingly contradictory
      repetition of the adage "Good fences make good neighbors," and the opening
      "something there is that doesn't love a wall," Frost mischievously navigates
      through the many meanings and functions of boundaries; how they separate, unite,
      and ultimately, how they might mend. Mending Wall offers physicians an
      opportunity to look closely at the barriers and thresholds prevalent in medicine
      and explore how they both preclude and allow for intimate and healing
      relationships.

PMID- 28455644
TI  - Treatment of Pediatric Chronic Kidney Disease-Mineral and Bone Disorder.
AB  - PURPOSE OF REVIEW: In this paper, we review the pathogenesis and treatment of
      chronic kidney disease-mineral and bone disorder (CKD-MBD), especially as it
      relates to pediatric CKD patients. RECENT FINDINGS: Disordered regulation of bone
      and mineral metabolism in CKD may result in fractures, skeletal deformities, and
      poor growth, which is especially relevant for pediatric CKD patients. Moreover,
      CKD-MBD may result in extra-skeletal calcification and cardiovascular morbidity.
      Early increases in fibroblast growth factor 23 (FGF23) levels play a key, primary
      role in CKD-MBD pathogenesis. Therapeutic approaches in pediatric CKD-MBD aim to
      minimize complications to the growing skeleton and prevent extra-skeletal
      calcifications, mainly by addressing hyperphosphatemia and secondary
      hyperparathyroidism. Ongoing clinical trials are focused on assessing the benefit
      of FGF23 reduction in CKD. CKD-MBD is a systemic disorder that has significant
      clinical implications. Treatment of CKD-MBD in children requires special
      consideration in order to maximize growth, optimize skeletal health, and prevent
      cardiovascular disease.

PMID- 28455646
TI  - Controlling Hypertension: We Have the Tools-We Just Need to Use Them.

PMID- 28455647
TI  - CMML: Clinical and molecular aspects.
AB  - Chronic Myelomonocytic Leukemia is a chronic myeloid neoplasm occurring mostly in
      the elderly with overlapping features of myelodysplastic syndromes (MDS) and
      myeloproliferative neoplasms (MPN) characterized by chronic monocytosis. Recent
      progresses in the molecular and cellular pathogenesis of CMML have stirred a
      renewed interest in this clinically heterogeneous disorder. Here, we review the
      recent progresses in the biology of CMML and how it affects its current and
      future clinical management.

PMID- 28455648
TI  - Overexpression of PSP1 enhances growth of transgenic Arabidopsis plants under
      ambient air conditions.
AB  - The importance of the phosphorylated pathway (PPSB) of L-serine (Ser)
      biosynthesis in plant growth and development has been demonstrated, but its
      specific role in leaves and interaction with photorespiration, the main leaf Ser
      biosynthetic pathway at daytime, are still unclear. To investigate whether
      changes in biosynthesis of Ser by the PPSB in leaves could have an impact on
      photorespiration and plant growth, we overexpressed PSP1, the last enzyme of this
      pathway, under control of the Cauliflower Mosaic Virus 35S promoter in
      Arabidopsis thaliana. Overexpressor plants grown in normal air displayed larger
      rosette diameter and leaf area as well as higher fresh and dry weight than the
      wild type. By contrast, no statistically significant differences to the wild type
      were observed when the overexpressor seedlings were transferred to elevated CO2,
      indicating a relationship between PSP1 overexpression and photorespiration.
      Additionally, the transgenic plants displayed higher photorespiration, an
      increase in CO2 net-uptake and stronger expression in the light of genes encoding
      enzymes involved in photorespiration. We further demonstrated that expression of
      many genes involved in nitrogen assimilation was also promoted in leaves of
      transgenic plants and that leaf nitrate reductase activity increased in the
      light, too, although not in the dark. Our results suggest a close correlation
      between the function of PPSB and photorespiration, and also nitrogen metabolism
      in leaves.

PMID- 28455649
TI  - Human parainfluenza virus type 2 V protein inhibits induction of tetherin.
AB  - Tetherin is an anti-viral factor that restricts viral budding through tethering
      virions to the cell surface. The human parainfluenza virus type 2 (hPIV-2) V
      protein decreases cell surface tetherin in HeLa cells, which constitutively
      express endogenous tetherin. However, the role of the hPIV-2 V protein in
      tetherin induction remains unclear. Here, we examined whether hPIV-2 infection
      itself induces tetherin in HEK293 cells that have no basal expression of
      tetherin. Unlike influenza A virus (IAV) infection, hPIV-2 infection induced
      neither tetherin mRNA nor protein expression. In contrast, robust tetherin
      induction was observed by infection of rPIV-2s carrying V mutants, in which
      either three Trp residues (W178H/W182E/W192A) or Cys residues (C209/211/214A)
      that are important for decreasing cell surface tetherin are mutated. hPIV-2
      infection also inhibited the induction of tetherin expression by IFN-alpha and
      IAV infection. Furthermore, hPIV-2 V protein but not P and VW178H/W182E/W192A
      suppressed tetherin induction. Our data collectively suggest that the hPIV-2 V
      protein inhibits tetherin expression induced by several external stimuli.

PMID- 28455650
TI  - [Use of cognitive aids in pediatric emergency care : Interdisciplinary consensus
      statement].
AB  - Preclinical pediatric emergencies are rare events and are therefore often
      associated with stress and uncertainty for emergency medical service personnel.
      To ensure adequate treatment of pediatric patients a variety of different
      cognitive aids exist (e.g. books, apps, rulers, weight-adapted bag systems).
      Especially the size specifications of the medical equipment and the dosage of
      emergency medication are individually very different in children and are
      dependent on parameters, such as body height and weight. Therefore, cognitive
      aids often enable length measurement whereby it is possible to draw conclusions
      on body weight for calculating the child's medication dosage. These aids may help
      to avoid the wrong medication dose or the wrong therapy of children but
      uncritical and untrained usage of these aids carries a potential risk of
      mistakes. This recommendation gives an overview of the general requirements and
      different problems of cognitive aids and should help improve the general
      framework and the rational basis for the use and further development of cognitive
      aids in emergency medicine.

PMID- 28455652
TI  - Attentional capture by spatiotemporally task-irrelevant faces: supportive
      evidence for Sato and Kawahara (2015).
AB  - Visual attention is captured exogenously by stimuli that are congruent with the
      viewer's current behavioral goals or intentions. However, Sato and Kawahara
      (Psychol Res 79:523-533, 2015) recently suggested that distractor faces capture
      attention in an entirely stimulus-driven manner without top-down control of
      attention, which then attenuates subsequent target identification, using a rapid
      serial visual presentation paradigm. We tested this suggestion, developing a
      hypothesis that the faces used in the previous study served as task-relevant
      temporal cues that predicted target timing. To evaluate this hypothesis, we
      eliminated the task relevance by widely varying distractor-target temporal lags
      (Experiment 1) and by counterbalancing the distractor-target temporal order
      (Experiment 2). In both experiments, the deterioration in performance resulting
      from attentional capture by the peripheral distractor face preceding the target
      remained robust; this effect was, however, eliminated when the face was inverted
      (Experiment 3). The present results provide clear evidence that upright faces
      capture attention exogenously even when they are spatiotemporally task
      irrelevant.

PMID- 28455651
TI  - [Management of hemorrhage in patients treated with direct oral anticoagulants].
AB  - The introduction of nonvitamin K antagonistic, direct oral anticoagulants (DOAC)
      made thromboembolic prophylaxis easier for patients. For many physicians,
      however, there is still uncertainty about monitoring, preoperative
      discontinuation, and restarting of DOAC therapy. Guidelines for the management of
      bleeding are provided, but require specific therapeutic skills in the management
      of diagnostics and therapy of acute hemorrhage. Small clinical studies and case
      reports indicate that unspecific therapy with prothrombin complex concentrates
      (PCC) and activated PCC (aPCC) concentrate may reverse DOAC-induced
      anticoagulation. However, PCC or aPCC at higher doses potentially provoke
      thromboembolic complications. However, idarucizumab, a specific, fast-acting,
      antidote for dabigatran, provides immediate and sustained reversal with no
      intrinsic or prohemostatic activity. This review article provides an overview of
      the pharmacology and potential risk of DOAC and the management in the
      perioperative period with a focus of current concepts in the treatment of DOAC
      associated bleeding.

PMID- 28455653
TI  - High prevalence of antibodies reacting to mimotopes of Simian virus 40 large T
      antigen, the oncoprotein, in serum samples of patients affected by non-Hodgkin
      lymphoma.
AB  - A new immunological investigation was carried out to study the association
      between non-Hodgkin lymphoma and Simian virus 40 (SV40). To this end, a new
      indirect ELISA was employed with two mimotopes from SV40 large T antigen (Tag),
      the viral oncoprotein, to analyse for specific reactions to antibodies in sera
      from non-Hodgkin lymphoma patients and controls, represented by healthy subjects
      (HS) and breast carcinoma (BC) patients. This study allowed us to assay a new
      sera collection from non-Hodgkin lymphoma patients (NHL, n = 254). To verify the
      association between NHL and SV40 Tag, two totally independent cohorts were
      analysed: NHL1 n = 150 and NHL2 n = 104. The epidemiological survey included sera
      from HS1, n = 150; HS2, n = 104 and BC, n = 78. This new indirect ELISA revealed
      that antibodies against SV40 Tag mimotopes are detectable in NHL1 and NHL2 sera
      with a prevalence of 37 and 36%, respectively. The prevalence of SV40-antibodies
      detected in both NHL1 and NHL2 cohorts differs statistically from controls, at
      19% for HS1 (p < 0.01), HS2 (p < 0.05) and BC patients (p < 0.05). This study,
      carried out with an immunological assay with specific Tag oncoprotein mimotopes
      of Simian virus 40, reports the presence of IgG antibodies against the large
      Tumour antigen in non-Hodgkin lymphomas for the first time. Our immunological
      data with two independent NHL cohorts show a statistically significant
      association between Simian virus 40 Tag and non-Hodgkin lymphoma. These results
      suggest that SV40-positive non-Hodgkin lymphomas could be treated differently
      from those tested SV40-negative.

PMID- 28455655
TI  - Greenlight(r) users should move from photoselective vaporization to endoscopic
      enucleation in larger prostates.

PMID- 28455654
TI  - Metabolically inactive insulin analogue does not prevent autoimmune diabetes in
      NOD mice.
AB  - AIMS/HYPOTHESIS: Insulin is widely considered to be a driver antigen in type 1
      diabetes in humans and in mouse models of the disease. Therefore, insulin or
      insulin analogues are candidates for tolerogenic drugs to prevent disease onset
      in individuals with risk of diabetes. Previous experiments have shown that
      autoimmune diabetes can be prevented in NOD mice by repeated doses of insulin
      administered via an oral, nasal or parenteral route, but clinical trials in
      humans have not succeeded. The hypoglycaemic activity of insulin is dose-limiting
      in clinical studies attempting tolerance and disease prevention. Here, we aimed
      to investigate the therapeutic potential of metabolically inactive insulin
      analogue (MII) in NOD mice. METHODS: The tolerogenic potential of MII to prevent
      autoimmune diabetes was studied by administering multiple i.v. or s.c. injections
      of MII to non-diabetic 7-12-week-old female NOD mice in three geographical colony
      locations. The incidence of diabetes was assessed from daily or weekly blood
      glucose measurements. The effect of MII on insulin autoantibody levels was
      studied using an electrochemiluminescence-based insulin autoantibody assay. The
      effect on the number of insulin-reactive CD8+ and CD4+ T lymphocytes in
      peripheral lymphoid tissue was studied with MHC class I and MHC class II
      tetramers, respectively. RESULTS: We found that twice-weekly s.c. administration
      of MII accelerates rather than prevents diabetes. High-dose i.v. treatment did
      not prevent disease or affect insulin autoantibody levels, but it increased the
      amount of insulin-reactive CD4+ T lymphocytes in peripheral lymphoid tissue.
      CONCLUSIONS/INTERPRETATION: Our data suggest that parenteral MII, even when used
      in high doses, has little or no therapeutic potential in NOD mice and may
      exacerbate disease.

PMID- 28455656
TI  - Nomogram predicting long-term survival after the diagnosis of intrahepatic
      recurrence of hepatocellular carcinoma following an initial liver resection:
      methodological issues.

PMID- 28455657
TI  - [Prostate artery embolization (PAE) : Technique and results].
AB  - CLINICAL/METHODICAL ISSUE: In the treatment of the benign prostatic hyperplasia
      (BPH) medical and surgical therapies have been established. STANDARD RADIOLOGICAL
      METHODS: Prostate artery embolization (PAE) is an innovative endovascular
      technique that might close the gap between both these procedures. PERFORMANCE:
      The PAE procedure is safe and has a low incidence of side effects. The efficacy
      of PAE has been proven for medium sized and large sized glands as well as for
      intravesical protrusions. ACHIEVEMENTS: The complex mechanism of PAE carries the
      potential to cure lower urinary tract symptoms as well as to retard the
      progression of the hyperplasia. PRACTICAL RECOMMENDATIONS: Data concerning the
      long-term efficacy are missing at present.

PMID- 28455658
TI  - Hemodialysis is associated with higher serum FGF23 level when compared with
      peritoneal dialysis.
AB  - BACKGROUND: Considering the growing relevance of fibroblast growth factor-23
      (FGF23) and increased cardiovascular mortality in dialysis population, an
      analysis was performed to assess the influence of dialysis modality (peritoneal
      dialysis and hemodialysis) on level of FGF23. METHODS: A cross-sectional study
      was performed in 80 continuous ambulatory peritoneal dialysis (CAPD) and 65
      hemodialysis (HD) patients without residual renal function. Levels of calcium,
      phosphate, parathyroid hormone and FGF23 were measured, and their correlations
      were analyzed. Data on demographics, dialysis modality and FGF23 level were also
      analyzed. RESULTS: A significant correlation was found between FGF23 and serum
      calcium, serum phosphate and dialysis vintage in dialysis patients. Level of
      FGF23 was significantly higher in hemodialysis patients than that in peritoneal
      dialysis population. Multivariable regression revealed that, compared to CAPD,
      hemodialysis was found to be a predictor for higher FGF23 level, which was
      independent of serum calcium and phosphate level (P < 0.05). CONCLUSIONS: These
      findings demonstrate that FGF23 levels are significantly higher in hemodialysis
      patients than that in peritoneal dialysis patients. We demonstrate an important
      association between dialysis modality (HD vs CAPD) and higher FGF23, independent
      of classical determinants (serum calcium and phosphate level).

PMID- 28455659
TI  - Differential expression of circulating miR-21, miR-142-3p and miR-155 in renal
      transplant recipients with impaired graft function.
AB  - BACKGROUND: The discovery of circulating microRNAs (miRNAs), as potential
      noninvasive diagnostic biomarkers, has opened new avenues of research for
      identifying patients with chronic failure in renal transplantation. The present
      study aimed to investigate the expression levels of four immune-related miRNAs
      (miR-21, miR-31, miR-142-3p and miR-155) in plasma samples of renal recipients.
      METHODS: The plasma expression levels of the miRNAs were evaluated by
      quantitative real-time PCR (qPCR) in 53 renal recipients with long-term stable
      allograft function, SGF (N = 27), and with biopsy-proven interstitial fibrosis
      and tubular atrophy (IFTA) (N = 26) and also healthy controls (N = 15). The
      possible correlation between clinical parameters and the circulating miRNAs and
      the receiver-operating characteristic (ROC) analysis were performed. RESULTS: Our
      results showed that expression of miR-21 (p = 0.023), miR-142-3p (p = 0.048) and
      miR-155 (p = 0.005) was significantly upregulated in plasma samples of recipients
      with IFTA in comparison with SGF and healthy control groups. Concentration of miR
      21 (?Ct value) in plasma was negatively correlated with creatinine (r = -0.432, p
      = 0.028) and positively correlated with eGFR (r = 0.423, p = 0.031). The
      multivariate ROC curve analysis indicated that miR-21, miR-142-3p and miR-155 in
      plasma samples could discriminate almost most of the IFTA patients (area under
      curve = 0.802, sensitivity = 81%, specificity = 92%). CONCLUSION: Our data
      suggested that altered expression of miR-21, miR-142-3p and miR-155 in plasma
      samples may be associated with renal dysfunction and can be used for graft
      monitoring.

PMID- 28455660
TI  - Radial artery sclerostin expression in chronic kidney disease stage 5 predialysis
      patients: a cross-sectional observational study.
AB  - PURPOSE: Bone metabolism disorder is often associated with cardiovascular
      calcification in patients with chronic kidney disease (CKD). Sclerostin, a novel
      candidate protein, has been identified to be involved in the bone-vascular axis.
      The aims of the current investigation were to assess vessel sclerostin expression
      and its relationship with circulating sclerostin levels. METHODS: A cross
      sectional observational study was conducted from January 2012 to December 2014.
      Thirty-two predialysis patients with CKD stage 5 who received arteriovenous
      fistula (AVF) operations were enrolled in this study. Radial arteries were
      collected and paraffin-embedded during the AVF operation, followed by
      immunohistochemical staining for sclerostin expression. In addition, serum
      sclerostin levels were measured by the enzyme-linked immunosorbent assay.
      RESULTS: The prevalence of positive sclerostin staining in the radial arteries
      was 56.25%. Sclerostin expression was localized in the artery media layer. Serum
      sclerostin levels in patients with positive sclerostin expression were much
      higher than in those with negative expression (p = 0.018). Multivariate logistic
      regression analyses including potential confounders as age, gender, systolic
      blood pressure (BP), diastolic BP, serum sclerostin, corrected calcium (Ca),
      phosphate (P), Ca * P product, alkaline phosphatase, intact parathyroid hormone,
      and estimated glomerular filtration rate showed that only serum sclerostin levels
      were closely related to vessel sclerostin expression (p = 0.025). The area under
      the curve of serum sclerostin levels for predicting positive vessel sclerostin
      expression was 0.742 with 61.1% sensitivity and 85.7% specificity (p  = 0.008).
      The cutoff point for vessel sclerostin expression of serum sclerostin was 1591.53
      pg/mL. CONCLUSIONS: Positive expression of sclerostin in the radial artery media
      layer was related to high serum sclerostin levels. Sclerostin may act as both a
      local and systemic regulator involved in vascular calcification.

PMID- 28455661
TI  - Modified laparoscopic placement of peritoneal dialysis catheter with intra
      abdominal fixation.
AB  - PURPOSE: Peritoneal dialysis (PD) is a commonly accepted method of treating end
      stage renal disease (ESRD). Various laparoscopic techniques for the placement of
      PD catheter have been described. In this study, we developed a novel modified
      laparoscopic technique for PD catheter placement and evaluated the early results.
      METHODS: A straight Tenckhoff PD catheter was placed employing the modified
      technique in 39 consecutive patients with ESRD from May 2013 to April 2016. The
      technique is laparoscopically guided intra-abdominal fixation of the PD catheter
      tip at one point by using suture passer hernia forceps. Individual information
      including sex, age, primary disease etiology, complications, surgical duration,
      morbidity, mortality and catheter survival was collected and analyzed. RESULTS:
      The modified laparoscopic procedure was effectively performed in all patients
      with a mean operative time of 45 +/- 7 min. No conversions from laparoscopy to
      open surgery of catheter placement occurred. There was one case showing early
      pericatheter leakage. There were no serious complications, such as bleeding,
      abdominal wall hernias, distal catheter cuff extrusion and infections of the exit
      site or tunnel during surgery or the postoperative duration. No mortality was
      observed in this group of patients. The 6-month follow-up study showed 100%
      catheter-related complication-free survival. CONCLUSIONS: Our modified
      laparoscopic intra-abdominal fixation technique using suture passer hernia
      forceps is a simple and safe method for PD catheter placement and is effective in
      minimizing the risk of catheter migration.

PMID- 28455662
TI  - Close correlation between the ankle-brachial index and symptoms of depression in
      hemodialysis patients.
AB  - BACKGROUND: As both of peripheral arterial disease (PAD) and depression carried a
      poor prognosis in patients on maintenance hemodialysis (MHD), we investigated the
      correlation between the ankle-brachial index (ABI), an indicator of subclinical
      PAD, and symptoms of depression in patients on MHD. METHODS: One hundred and
      twenty-nine patients on MHD (75 males and 54 females, mean age 64.8 +/- 12 years)
      were enrolled in this cross-sectional study, which aimed at evaluating the
      relationship between symptoms of depression and ABI. Demographic as well as
      clinical and laboratory variables including status of diabetes, chronic hepatitis
      C infection, dialysis duration, Charlson comorbidity index (CCI), plasma levels
      of albumin, C-peptide, insulin, high-sensitive C-reactive protein (hsCRP),
      interleukin-6 (IL-6), adiponectin, and lipid profile were obtained. The self
      administered beck depression inventory (BDI) was used to determine the presence
      or absence of symptoms of depression, and depression was defined as a BDI score
      ?14. Multivariable-adjusted linear regression models were constructed to confirm
      the independent association of biologic parameters of symptoms of depression.
      Significance was defined as P < 0.05. Statistical analyses were performed using
      SPSS/Windows software (SPSS Science, v. 15.0, Chicago, IL). RESULTS: The mode of
      multivariate analysis showed that diabetes (beta = 3.594; P = 0.040), hepatitis C
      infection (beta = 4.057; P = 0.008), levels of serum albumin (beta = -5.656; P =
      0.024), C-peptide (beta = -0.292; P = 0.002), ABI (beta = -9.041; P = 0.031), and
      Ln-transformed hsCRP were significantly associated with BDI. CONCLUSIONS:
      Hepatitis C infection, serum levels of albumin, C-peptide, and ABI levels were
      found to be correlated with BDI (P < 0.05).

PMID- 28455663
TI  - Predictors and outcomes of non-adherence in patients receiving maintenance
      hemodialysis.
AB  - PURPOSE: Predictors of and outcomes associated with non-adherent behavior among
      patients on chronic hemodialysis (HD) have been incompletely elucidated. We
      conducted a post hoc analysis of data from the SMILE trial to identify patient
      factors associated with non-adherence to dialysis-related treatments and the
      associations of non-adherence with clinical outcomes. METHODS: We defined non
      adherence as missed HD and abbreviated HD. We used negative binomial regression
      to model the associations of demographic and clinical factors with measures of
      non-adherence, and negative binomial and Cox regression to analyze the
      associations of non-adherence with hospitalizations and mortality, respectively.
      RESULTS: We followed 286 patients for up to 24 months. Factors independently
      associated with missing HD included Tuesday/Thursday/Saturday HD schedule
      [incident rate ratio (IRR) 1.85, p < 0.01], current smoking (IRR 2.22, p < 0.01),
      higher pain score (IRR 1.04, p < 0.01), lower healthy literacy (IRR 3.01, p <
      0.01), lower baseline quality of life (IRR 0.89, p = 0.01), and younger age (IRR
      1.35, p < 0.01). Factors independently associated with abbreviating HD included
      dialysis vintage (IRR 1.07, p < 0.01), higher pain score (IRR 1.02, p < 0.01),
      current non-smoking (IRR 1.32, p = 0.03), and younger age (IRR 1.22, p < 0.01).
      Abbreviating HD was independently associated with an increased number of total
      (IRR 1.70, p < 0.01) and ESRD-related (IRR 1.66, p < 0.01) hospitalizations,
      while missing HD was independently associated with mortality (HR 2.36, p = 0.04).
      CONCLUSIONS: We identified several previously described and novel factors
      independently associated with non-adherence to HD-related treatments, and
      independent associations of non-adherence with hospitalization and mortality.
      These findings should inform the development and implementation of interventions
      to improve adherence and reduce health resource utilization.

PMID- 28455664
TI  - Proteomic analysis of astaxanthin biosynthesis in Xanthophyllomyces dendrorhous
      in response to low carbon levels.
AB  - The ratio of carbon to nitrogen (C/N) in media plays a crucial role in the
      production of microbial carotenoids. However, the effects of a high C/N ratio on
      carotenoid production are ambiguous, and the mechanism of how C/N ratio affects
      astaxanthin accumulation in X. dendrorhous is unclear. In this study, the
      influence of C/N ratio on astaxanthin biosynthesis in X. dendrorhous at a fixed
      nitrogen concentration was investigated, and comparative proteomics were applied
      to address how C/N ratio affects cell growth and astaxanthin accumulation in X.
      dendrorhous. The results showed that cell growth and astaxanthin accumulation in
      X. dendrorhous were strongly related to the ratio of carbon to nitrogen with
      increasing C/N ratio in medium. However, the astaxanthin content per cell showed
      an inverse relationship, decreasing with an increasing C/N ratio. Differential
      proteomics showed the proteins with highest degree of change in expression under
      varying C/N ratios were mainly involved in carbohydrate metabolic pathways and
      carotenogenesis metabolism. In addition, several redox- and stress-associated
      proteins were up-regulated along with the carotenogenesis proteins, implying the
      environmental stress may affect metabolism and astaxanthin synthesis. A possible
      regulatory mechanism in response to glucose in X. dendrorhous is discussed.

PMID- 28455665
TI  - Cross-coupling vestibular stimulation: motion sickness and the vestibulo
      sympathetic reflex.
AB  - Motion sickness is associated with a variety of autonomic symptoms, presumably
      due to proximity or functional interconnectivity between the autonomic centers in
      the brainstem and the vestibular system. A direct influence of the vestibular
      system on cardiovascular variables, defined as the vestibulo-sympathetic reflex,
      has been reported previously. Our aim was to investigate the sudomotor components
      of the autonomic responses associated with motion sickness during passive cross
      coupling stimulation ("roll while rotating"). Healthy subjects (n = 17) were
      rotated at 40 degrees /s around an earth-vertical yaw axis alone and in
      combination with sinusoidal roll oscillations (0.2 Hz). Motion sickness was
      assessed verbally every minute using a 1-10 scale, while recording DC and AC skin
      conductance levels (SCL) from the forehead. Yaw rotation alone provoked neither
      motion sickness nor variations of forehead sweating. Yet during cross-coupling
      stimulation all subjects reported motion sickness. Higher motion sickness scores
      (>5) were associated with significantly higher amplitudes of AC-SCL events
      compared to the lower scores (0.22 +/- 0.01 vs. 0.11 +/- 0.01 uS, respectively).
      Frequency domain analysis of the AC-SCL events revealed a peak at 0.2 Hz,
      coinciding with the frequency of the chair rolls. The total power of AC-SCL
      signals did not match the trend of motion sickness scores across conditions. We
      conclude that: (1) although SCL is related to motion sickness, it does not follow
      the perceived sickness closely; (2) the discrepancy between SCL and motion
      sickness and the rhythmic AC-SCL events could reflect a sudomotor component of
      the vestibulo-sympathetic reflex.

PMID- 28455666
TI  - Revisiting 'progressive stroke': incidence, predictors, pathophysiology, and
      management of unexplained early neurological deterioration following acute
      ischemic stroke.
AB  - Early neurological deterioration (END) following acute ischemic stroke is a
      serious clinical event strongly associated with poor outcome. Regarding
      specifically END occurring within 24 h following stroke onset, apart from
      straightforward causes such as symptomatic intracranial haemorrhage and malignant
      edema, the cause of END remains unclear in more than a half of cases. In the
      latter situation, patients are often referred to as 'progressive stroke', a
      default clinical category that does not imply underlying mechanisms, precluding
      informed management. In this review article, we summarize the available evidence
      on the incidence, predictors, and associated factors of unexplained END, and
      discuss its underlying pathophysiology. We particularly address the hemodynamic
      and thrombotic mechanisms that likely play a critical role in unexplained END,
      and in turn highlight potential new avenues to prevent and manage this ominous
      event.

PMID- 28455667
TI  - Adult-onset ataxia or developmental disorder with seizures: two sides of missense
      changes in CACNA1A.

PMID- 28455668
TI  - Isolation and genomic characterization of a canine parainfluenza virus type 5
      strain in China.
AB  - A canine parainfluenza virus type 5 strain was isolated from a lung sample from a
      diseased dog. The genome sequene of this isolate, named HeN0718, was determined
      and compared tho those of other previously reported canine parainfluenza viruses.
      Unlike previously reported viruses, the HeN0718 strain contained several
      nucleotide mutations in the SH gene that led to a frame shift in the open reading
      frame. Phylogenetic analysis based on the complete virus genome and the P, F, and
      HN genes showed that HeN0718 was genetically closest to D277, a Korean strain
      that was isolated in 2008.

PMID- 28455669
TI  - Complete genome sequence of a new isolate of potato virus M in Yunnan, China.
AB  - The complete genome sequence of a new potato virus M (PVM) isolate (PVM-YN),
      collected from potato (Solanum tuberosum) in Yunnan, China, was determined. It
      was 8,530 nucleotides (nt) in length, excluding the poly(A) tail at the 3' end,
      and shared 71.4-72.0% nucleotide sequence identity with available PVM isolates in
      the NCBI database. The coat proteins (CP) of PVM-YN shared 79.0-97.4% amino acid
      sequence identity with that of other isolates. It is the first report of the
      complete genomic sequence of a new PVM isolate infecting S. tuberosum in China.

PMID- 28455670
TI  - Complete nucleotide sequence and annotation of the temperate corynephage phi16
      genome.
AB  - The complete genome of phi16, a temperate corynephage from Corynebacterium
      glutamicum ATCC 21792, was sequenced and annotated (GenBank: KY250482). The
      electron microscopy study of phi16 virion confirmed that it belongs to the family
      Siphoviridae. The phi16 genome consists of a linear double-stranded DNA molecule
      of 58,200 bp (G+C = 52.2%) with protruding cohesive 3'-ends of 14 nt. Four major
      structural proteins were separated by SDS-PAGE and identified by peptide mass
      fingerprinting technique. Using bioinformatics analysis, 101 putative ORFs and 5
      tRNA genes were predicted. Only 27 putative gene products could be assigned to
      known biological functions. The phi16 genome was divided into functional modules.
      Seven putative promoters and eight putative unidirectional intrinsic terminators
      were predicted. One site of putative "-1" programmed ribosomal frameshifting was
      proposed in the phage tail assembly genome region. C. glutamicum genetic tools
      could be broadened by exploiting the known integrase gene (gp33) and the newly
      identified excisionase gene (gp47), participating in site-specific recombination
      between phi16-attP/attB.

PMID- 28455671
TI  - Perceptions of Cervical Cancer Screening, Screening Behavior, and Post-Migration
      Living Difficulties Among Bhutanese-Nepali Refugee Women in the United States.
AB  - Bhutanese-Nepali refugees are one of the largest refugee groups to be resettled
      in the U.S. in the past decade. Cervical cancer is a leading cause of cancer
      disparity in this population, yet screening rates are suboptimal. Nepali-speaking
      interviewers administered a community health needs questionnaire to a convenience
      sample of Bhutanese-Nepali refugees in a Midwestern city between July to October
      of 2015. Descriptive statistics were used to describe socio-demographic
      characteristics, Pap smear beliefs, post-migration living difficulties, and
      screening status. Differences in Pap test uptake between groups were tested using
      t test and Chi square statistics. Of the 97 female participants, 44.3% reported
      ever having had a Pap smear. Screening rates were lowest among women who did not
      know English at all. Most women had positive perceptions of Pap smears (80%) and
      44.4% had received a Pap test recommendation from their healthcare provider,
      family, or friends. Pap testing was significantly higher among those who had
      positive perceptions (58.3 vs. 11.1% for women of negative perception, p = 0.01)
      and those who had received a recommendation (87.5 vs. 18.6% for women who had no
      recommendations, p < 0.001). Significant predictors of having a Pap smear were
      having a healthcare provider/family/friends recommendation (OR 65.3, 95% CI 11.4
      373.3) and greater number of post-migration living difficulties (OR 1.18, 95% CI
      1.02-1.37). The results of this study have important implications for the
      development of cervical cancer prevention programs targeting Bhutanese-Nepali
      refugees. Providing cancer prevention interventions early in the resettlement
      process could impact Pap test uptake in this population.

PMID- 28455672
TI  - Race is a Strong Predictor of Receipt of a Written Survivorship Care Plan:
      Results from the National Health Interview Survey.
AB  - The purpose of this study is to investigate the prevalence of receipt of written
      documentation of follow up care and of cancer treatments and to examine the
      predictors of receipt of such written documentation. Data from the 2010 National
      Health Interview Survey was used to identify individuals 18 years or older with a
      history of cancer. Binary and multinomial logistic regression were used to
      investigate patient-level variables associated with receipt of written
      documentation of cancer treatment, written advice about follow-up care, or both
      written documents. Patient-level variables included in the analysis were age,
      gender, region of residence, race/ethnicity, marital status, education level,
      insurance coverage, cancer type, employment status, and psychosocial support. Of
      the 1185 responses to the questions used to access receipt of a SCP, the
      prevalence of any receipt of a written documentation was 68%, where 30% obtained
      written advice only and 8% were provided a written treatment summary only; only
      31% received both. Non-white race, cancer type, and psychosocial services were
      associated with increased odds of receiving written documentation. Patient-level
      characteristics are associated with receipt of care plan documentation. Further
      work needs to investigate the interaction of provider and patient-level
      characteristics. Understanding patient-level characteristics associated with
      receipt of written documentation may help uncover strategies for improved
      survivorship care plan implementation.

PMID- 28455673
TI  - Population-Based Analysis of Breast Cancer Incidence and Survival Outcomes in
      Women Diagnosed with Lobular Carcinoma In Situ.
AB  - PURPOSE: A diagnosis of lobular carcinoma in situ (LCIS) is associated with an
      increased risk of developing breast cancer, although little data exist on long
      term patient outcomes, including those who develop subsequent breast
      malignancies. METHODS: The Surveillance, Epidemiology, and End Results (SEER)
      database was used to identify women with a histological diagnosis of LCIS between
      1983 and 2014. The incidence and clinicopathologic features of subsequent
      malignancies were then examined, and the Kaplan-Meier method and multivariable
      Cox PH regression used to obtain breast cancer-specific survival (BCSS) estimates
      and associated hazard ratios. RESULTS: Overall, 19,462 women swith a mean age at
      LCIS diagnosis of 53.7 years, and a 10- and 20-year cumulative incidence of
      subsequent breast malignancy of 11.3% [95% confidence interval (CI) 10.7-11.9%]
      and 19.8% (95% CI 18.8-20.9) met the eligibility criteria. At a median follow-up
      of 8.1 years (range 0-30.9) a total of 1837 primary breast cancers were
      diagnosed, of which 55.2% were diagnosed in the ipsilateral breast. Most breast
      cancers were of low/intermediate grade, hormone receptor-positive, and diagnosed
      in early stages. Of subsequent malignancies, invasive ductal carcinoma (IDC)
      distributed equally across both breasts, whereas invasive lobular carcinoma (ILC)
      was more likely to present in the ipsilateral breast (69.0% ILC vs. 49.2% IDC; p
      < 0.001). On multivariable analysis, type of surgical treatment for LCIS had no
      affect on long-term survival (p = 0.44). The 10- and 20-year BCSS for women with
      LCIS was 98.9 and 96.3%, respectively. CONCLUSION: Women with LCIS who are
      diagnosed with a subsequent primary breast cancer are often diagnosed in early
      stages and have excellent BCSS.

PMID- 28455674
TI  - Androgens and Hypertension in Men and Women: a Unifying View.
AB  - PURPOSE OF REVIEW: This review was designed to revaluate the androgen role on the
      mechanisms of hypertension and cardiovascular risks in both men and women. Sex
      steroids are involved in the regulation of blood pressure, but pathophysiological
      mechanism is not well understood. Androgens have an important effect on
      metabolism, adipose and endothelial cell function, and cardiovascular risk in
      both men and women. A focal point in this contest is represented by the possible
      gender-specific regulation of different tissues and in particular of the adipose
      cell. Available data confirm that androgen deficiency is linked to increased
      prevalence of hypertension and cardiovascular diseases. Adipocyte dysfunction
      seems to be the main involved mechanism. Androgen replacement reduces
      inflammation state in man, protecting by metabolic syndrome progression. In
      women, androgen excess has been considered as promoting factor of cardiovascular
      risk. However, recent data suggest that excessive androgen production has little
      effect per se in inducing hypertension in young women of reproductive age. Also
      in postmenopausal women, data on relative androgen excess and hypertension are
      missing, while adrenal androgen deficiency has been associated to increased
      mortality. RECENT FINDINGS: Molecular mechanisms linking androgen dysregulation
      to hypertension are almost Unknown, but they seem to be related to increased
      visceral fat, promoting a chronic inflammatory state through different
      mechanisms. One of these may involve the recruitment and over-activation of NF
      kB, a ubiquitous transcription factor also expressed in adipose cells, where it
      may cause the production of cytokines and other immune factors. The NF-kB
      signalling pathway may also influence brown adipogenesis leading to the
      preferential enlargement of visceral adipocytes. Chronic inflammation and
      adipocyte dysfunction may alter endothelial function leading to hypertension.
      Both in men and in women, particularly in the post-menopausal period,
      hypoandrogenism seems to be a major determinant of the increased prevalence of
      hypertension. The relationship between androgen signalling and NF-kB might
      explain the pathophysiological mechanism leading to the development of
      endothelium dysfunction and hypertension.

PMID- 28455675
TI  - Relationship between size of disc and early postoperative outcomes after lumbar
      discectomy.
AB  - BACKGROUND: Previous studies suggest that patients with larger disc herniations
      (greater than 6 mm) will have better outcomes following discectomy. This has not
      been validated in a large series of patients. PURPOSE: We sought to empirically
      evaluate this relationship in a series of patients who had data collected
      prospectively as part of a randomized trial. METHODS: This retrospective review
      included 63 consecutive adult patients who underwent a single-level, primary
      lumbar discectomy. Outcomes were VAS for leg and back pain and the modified
      oswestry disability index (MODI). Statistical tests were used to compare patients
      using different cutoffs of preoperative disc diameters and disc volume removed.
      Regression analysis was performed to determine if there was a relationship
      between outcomes and the measured parameters. RESULTS: While patients who
      achieved substantial clinical benefit (SCB) for MODI had larger disc diameters,
      this relationship was not found for leg or back pain for any of the measured
      parameters. Using 5, 6, 7, or 8 mm as a cutoff for disc diameter demonstrated no
      differences. Regression analysis did not demonstrate a significant relationship
      between disc volume removed and final MODI scores. CONCLUSION: While patients
      with larger disc herniations on average might have a greater likelihood of
      superior clinical outcomes, the previously suggested "6 mm rule" was not
      supported.

PMID- 28455676
TI  - Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by
      Cunninghamella elegans.
AB  - The knowledge of metabolic profile of synthetic cannabinoids is important for the
      detection of drugs in urinalysis due to the typical absence or low abundance of
      parent cannabinoids in human urine. The fungus Cunninghamella elegans has been
      reported to be a useful tool for metabolism study and thus applicability to
      synthetic cannabinoid metabolism was examined. In this study, 8-quinolinyl 1-(5
      fluoropentyl)-1H-indole-3-carboxylate (5F-PB-22), 8-quinolinyl 1-pentyl-1H-indole
      3-carboxylate (PB-22), [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3
      tetramethylcyclopropyl)methanone (XLR-11) and (1-pentyl-1H-indol-3-yl)(2,2,3,3
      tetramethylcyclopropyl)methanone (UR-144) were incubated with C. elegans and the
      metabolites were identified using liquid chromatography-quadrupole time-of-flight
      mass spectrometry. The obtained metabolites were compared with reported human
      metabolites to assess the suitability of the fungus to extrapolate human
      metabolism. 5F-PB-22 underwent dihydroxylation, dihydrodiol formation, oxidative
      defluorination, oxidative defluorination to carboxylic acid, ester hydrolysis and
      glucosidation, alone and/or in combination. The metabolites of PB-22 were
      generated by hydroxylation, dihydroxylation, trihydroxylation, dihydrodiol
      formation, ketone formation, carboxylation, ester hydrolysis and glucosidation,
      alone and/or in combination. XLR-11 was transformed through hydroxylation,
      dihydroxylation, aldehyde formation, carboxylation, oxidative defluorination,
      oxidative defluorination to carboxylic acid and glucosidation, alone and/or in
      combination. UR-144 was metabolised by hydroxylation, dihydroxylation,
      trihydroxylation, aldehyde formation, ketone formation, carboxylation, N
      dealkylation and combinations. These findings were consistent with previously
      reported human metabolism except for the small extent of ester hydrolysis
      observed and the absence of glucuronidation. Despite the limitations, C. elegans
      demonstrated the capacity to produce a wide variety of metabolites including some
      major human metabolites of XLR-11 and UR-144 at high abundance, showing the
      potential for metabolism of newly emerging synthetic cannabinoids.

PMID- 28455677
TI  - Obesity Prevention for Individuals with Spina Bifida.
AB  - PURPOSE OF REVIEW: Obesity is a common comorbidity in individuals with spina
      bifida. Carrying excess weight exacerbates the inherent health challenges
      associated with spina bifida, impedes the individual's ability to self-manage
      their condition, and creates further challenges for family members and
      caregivers. This manuscript provides a narrative review of key issues for
      understanding and prevention of obesity in persons with spina bifida within the
      context of the social ecological model. RECENT FINDINGS: Specific variables
      related to obesity and spina bifida include individual factors (i.e., body
      composition and measurement issues, energy needs, eating patterns, physical
      activity, and sedentary activity) family factors (i.e., parenting/family, peers),
      community factors (i.e., culture, built environment, healthcare and healthcare
      providers, and school), and societal factors (i.e., policy issues). Due to the
      complex etiology of obesity and its increased prevalence in individuals with
      spina bifida, it is critical to initiate prevention efforts early with a
      multifactorial approach for this at-risk population. Increased research is
      warranted to support these efforts.

PMID- 28455678
TI  - Early Nutrition and Physical Activity Interventions in Childhood Cancer
      Survivors.
AB  - PURPOSE OF REVIEW: Childhood cancer survivors experience excessive weight gain
      early in treatment. Lifestyle interventions need to be initiated early in cancer
      care to prevent the early onset of obesity and cardiovascular disease (CVD). We
      reviewed the existing literature on early lifestyle interventions in childhood
      cancer survivors and consider implications for clinical care. RECENT FINDINGS:
      Few lifestyle interventions focus on improving nutrition in childhood cancer
      survivors. A consistent effect on reducing obesity and CVD risk factors is not
      evident from the limited number of studies with heterogeneous intervention
      characteristics, although interventions with a longer duration and follow-up show
      more promising trends. Future lifestyle interventions should be of a longer
      duration and include a nutrition component. Interventions with a longer duration
      and follow-up are needed to assess the timing and sustainability of the
      intervention effect. Lifestyle interventions introduced early in cancer care are
      both safe and feasible.

PMID- 28455679
TI  - Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and
      Over.
AB  - PURPOSE OF REVIEW: One begins to see improvement in glycemic measures and
      triglycerides with small amounts of weight loss, but with greater levels of
      weight loss there is even greater improvement. In fact, the relationship between
      weight loss and glycemia is one that is very close. RECENT FINDINGS: This is
      fortunate for diabetes prevention; it takes only small amounts of weight loss to
      prevent progression to type 2 diabetes from impaired glucose tolerance, and after
      the 10 kg of weight loss, one cannot demonstrate much additional improvement in
      risk reduction. Modest weight loss (5 to 10%) is also associated with improvement
      in systolic and diastolic blood pressure and HDL cholesterol. With all these risk
      factors, more weight loss produces more improvement. Further, for patients with
      higher BMI levels (>40 kg/m2), the ability to lose the same proportion of weight
      with lifestyle intervention is equal to that of those with lower BMI levels, and
      there is equal benefit in terms of risk factor improvement with modest weight
      loss. For some comorbid conditions, more weight loss is needed-10 to 15%-to
      translate into clinical improvement. This is true with obstructive sleep apnea
      and non-alcoholic steatotic hepatitis. There is a graded improvement in
      improvements in measures of quality of life, depression, mobility, sexual
      dysfunction, and urinary stress incontinence, whereby improvements are
      demonstrable with modest weight loss (5-10%) and with further weight loss there
      are further improvements. For polycystic ovarian syndrome and infertility, modest
      weight loss (beginning at 2-5%) can bring improvements in menstrual
      irregularities and fertility. Moderate weight loss (5-10%) has been shown to be
      associated with reduced health care costs. Reduction in mortality may take more
      than 10% weight loss, although definitive studies have not been done to
      demonstrate that weight loss per se is associated with mortality reduction.
      Clinicians in medical weight management should bear in mind that the target
      should be health improvement rather than a number on the scale. The individual
      patient's targeted health goal should be assessed for response rather than a
      prescribed percentage weight loss.

PMID- 28455680
TI  - Directly measured free 25-hydroxy vitamin D levels show no evidence of vitamin D
      deficiency in young Swedish women with anorexia nervosa.
AB  - PURPOSE: Anorexia nervosa (AN) is an eating disorder characterized by low fat
      mass complicated by osteoporosis. The role of circulating vitamin D in the
      development of bone loss in AN is unclear. Fat mass is known to be inversely
      associated with vitamin D levels measured as serum levels of total, protein-bound
      25-hydroxyvitamin D, but the importance of directly measured, free levels of
      25(OH)D has not been determined in AN. The aim of this study was to investigate
      vitamin D status, as assessed by serum concentrations of total and free serum
      25(OH)D in patients with AN and healthy controls. METHODS: In female AN patients
      (n = 20), and healthy female controls (n = 78), total 25(OH)D was measured by LC
      MS/MS, and free 25(OH)D with ELISA. In patients with AN bone mineral density
      (BMD) was determined with DEXA. RESULTS: There were no differences between
      patients and controls in total or free S-25(OH)D levels (80 +/- 31 vs 72 +/- 18
      nmol/L, and 6.5 +/- 2.5 vs 5.6 +/- 1.8 pg/ml, respectively), and no association
      to BMD was found. In the entire group of patients and controls, both vitamin D
      parameters correlated with BMI, leptin, and PTH. CONCLUSIONS: The current study
      did not demonstrate a vitamin D deficiency in patients with AN and our data does
      not support vitamin D deficiency as a contributing factor to bone loss in AN.
      Instead, we observed a trend toward higher vitamin D levels in AN subjects
      compared to controls. Measurement of free vitamin D levels did not contribute to
      additional information.

PMID- 28455682
TI  - Shoplifting and eating disorders: an anonymous self-administered survey.
AB  - PURPOSE: To explore the characteristics of eating disorders related to
      shoplifting behavior and identify the risk and protective factors related to
      shoplifting among patients with eating disorders. METHODS: Eighty females with
      eating disorders were recruited from an eating disorders clinic. They were asked
      to complete anonymous self-report questionnaires on demographic characteristics,
      shoplifting behavior, psychological characteristics and eating disorder
      symptomology. We investigated differences in clinical characteristics between
      those with and without shoplifting history or a current drive to shoplift.
      RESULTS: The response rate was 92.5%. Of the respondents, 37.8% reported a
      history of shoplifting and 16.2% a current drive for shoplifting. The patients
      with shoplifting history had lower socioeconomic status (SES), higher impulsivity
      and higher symptom severity of eating disorders compared with those without this
      history. The patients with a current drive for shoplifting had more depressive
      symptoms, more severe anxiety, more obsessional traits, and higher symptom
      severity of eating disorders. CONCLUSIONS: Severity of illness and SES seem to
      have a serious impact on shoplifting behavior among eating disordered patients.
      These findings may suggest risk and protective factors related to shoplifting
      among eating disordered patients.

PMID- 28455684
TI  - So You Want to Publish in Lipids: Tips for Authors to Enhance Their Potential for
      Success.

PMID- 28455681
TI  - Multidimensional improvements induced by an intensive obesity inpatients
      rehabilitation programme.
AB  - PURPOSE: To analyse the short-term effectiveness of an intensive multidimensional
      inpatient programme specifically developed for patients with severe obesity.
      METHODS: A multidisciplinary team managed a 3-week residential programme
      characterised by the integration of nutritional and physical rehabilitation with
      psychological and educational intervention. All patients consecutively admitted
      in 10 months were analysed at admission and discharge for changes in the
      following domains: anthropometry (weight, body mass index (BMI), waist and neck
      circumferences), cardiovascular risk factors (glycaemia, HbA1c, lipid profile,
      blood pressure), quality of life, eating behaviour, and physical performance
      (VO2peak by incremental cycle ergometer test, 6-min walking test (6MWT), chair
      stands test). RESULTS: 136 subjects (61% females, median age 52.7 years) with
      obesity (mean BMI 43.2 kg/m2) and multiple comorbidities were analysed. A 3.9%
      BMI reduction and a reduction in waist (-3.8%) and neck (-3.3%) circumferences
      were observed. Glycaemic control was achieved in 68% of patients with
      uncontrolled diabetes at admission. Blood pressure control was achieved in all
      patients with uncontrolled hypertension at admission. Total cholesterol (-16%),
      LDL-cholesterol (-19%) and triglycerides (-9%) were significantly reduced.
      Psychometric assessment showed improvements in quality of life perception and
      binge eating disorder. Finally, a significant improvement in physical performance
      (+4.7% improvement in VO2peak, with longer distances in 6MWT and a higher number
      of standings) was observed. CONCLUSIONS: Our preliminary data prove that a 3-week
      programme determined a clinically significant multi-dimensional improvement in
      patients with severe obesity. Long-term follow-up data are needed to confirm the
      efficacy of our rehabilitation setting.

PMID- 28455685
TI  - Inferring Intracellular Signal Transduction Circuitry from Molecular Perturbation
      Experiments.
AB  - The development of network inference methodologies that accurately predict
      connectivity in dysregulated pathways may enable the rational selection of
      patient therapies. Accurately inferring an intracellular network from data
      remains a very challenging problem in molecular systems biology. Living cells
      integrate extremely robust circuits that exhibit significant heterogeneity, but
      still respond to external stimuli in predictable ways. This phenomenon allows us
      to introduce a network inference methodology that integrates measurements of
      protein activation from perturbation experiments. The methodology relies on logic
      based networks to provide a predictive approximation of the transfer of signals
      in a network. The approach presented was validated in silico with a set of test
      networks and applied to investigate the epidermal growth factor receptor
      signaling of a breast epithelial cell line, MFC10A. In our analysis, we predict
      the potential signaling circuitry most likely responsible for the experimental
      readouts of several proteins in the mitogen-activated protein kinase and
      phosphatidylinositol-3 kinase pathways. The approach can also be used to identify
      additional necessary perturbation experiments to distinguish between a set of
      possible candidate networks.

PMID- 28455686
TI  - Flightless-I homolog regulates glucocorticoid receptor-mediated transcription via
      direct interaction of the leucine-rich repeat domain.
AB  - Flightless-I homolog (FLII) is a member of the gelsolin family of proteins, and
      has been identified as a coactivator of estrogen receptor-mediated transcription.
      Here, we investigate the role of FLII in the glucocorticoid receptor (GR)
      signaling pathway. Reporter gene assay and real-time quantitative PCR in A549
      were performed to investigate the function of FLII in the expression of GR target
      genes. Co-immunoprecipitation assay and in vitro binding assay were used to
      identify binding domain of FLII. Chromatin immunoprecipitation assay were carried
      out with FLII-depleted A549 cells to determine the role of FLII at GR binding
      sites. We demonstrate that FLII potentiates GR-mediated reporter gene activity
      synergistically with CARM1 and p300 to enhance GR transcriptional activity in the
      presence of dexamethasone (Dex) in A549 cells. Depletion of endogenous FLII
      inhibited the expression of Dex-regulated GR target genes in A549 cells,
      indicating that FLII is required for GR-mediated transcription. Further, we
      observed that FLII binds to GR via its N-terminal leucine-rich repeat (LRR)
      region, suggesting that the enhancement of GR activation may occur through the
      interaction of GR and FLII. Moreover, chromatin immunoprecipitation analysis
      demonstrated that FLII is recruited to the GR binding sites. In addition,
      depletion of endogenous FLII decreased the recruitment of p300, and subsequently
      RNA polymerase II, to specific sites of GR target genes. Taken together, these
      studies reveal a functional involvement of FLII in activating transcription of GR
      target genes, suggesting a physiological role for FLII in the GR signaling
      pathway.

PMID- 28455687
TI  - Assessing Child Body Mass Index Perceptions Among African American Caregivers in
      a Rural Community.
AB  - In the USA, African American children residing in rural areas are
      disproportionately affected by childhood obesity. One strategy for preventing
      childhood obesity is helping caregivers to recognize their child is overweight or
      obese. The purpose of this study is to assess African American caregivers'
      perceived level of their child's obesity status and concordance between
      caregiver's reported height and weight of their children compared to the
      objective measure of their child's height and weight. Caregivers completed a
      paper-based survey about perceptions of their child's weight status including
      body silhouettes (n = 119) and self-reported their child's body mass index status
      (n = 68). Children's (n = 71) height and weight were objectively measured.
      Spearman rho and independent sample t tests were calculated to assess the
      relationship between caregiver's self-reported and objective BMI status.
      Caregiver's visually perceived their child's weight status to be underweight;
      yet, self-reported that their child's body mass index status was obese. The
      Spearman's rho correlation indicated a significant relationship between
      caregiver's self-reported and objective body mass index (r = .39, p < .001). The
      independent sample t test reflected that the mean self-reported body mass index
      and objective body mass index were statistically significant with calculated body
      mass index perception. The investigation of three different methods for assessing
      body mass index perceptions may contribute to the development of tailored
      programs and interventions that include counseling strategies that increase
      parental education about their child's body mass index.

PMID- 28455688
TI  - Detailed Structural Characterization of Sphingolipids via 193 nm Ultraviolet
      Photodissociation and Ultra High Resolution Tandem Mass Spectrometry.
AB  - Sphingolipids serve not only as components of cellular membranes but also as
      bioactive mediators of numerous cellular functions. As the biological activities
      of these lipids are dependent on their structures, and due to the limitations of
      conventional ion activation methods employed during tandem mass spectrometry
      (MS/MS), there is a recognized need for the development of improved structure
      specific methods for their comprehensive identification and characterization.
      Here, positive-ionization mode 193 nm ultraviolet photodissociation (UVPD)-MS/MS
      has been implemented for the detailed structural characterization of lipid
      species from a range of sphingolipid classes introduced to the mass spectrometer
      via electrospray ionization as their lithiated or protonated adducts. These
      include sphingosine d18:1(4E), dihydrosphingosine (sphinganine) d18:0,
      sphingadiene d18:2(4E,11Z), the isomeric sphingolipids ceramide d18:1(4E)/18:0
      and dihydroceramide d18:0/18:1(9Z), ceramide-1-phosphate d18:1(4Z)/16:0,
      sphingomyelin d18:1(4E)/18:1(9Z) the glycosphingolipids galactosyl ceramide
      d18:1(4E)/24:1(15Z) and lactosyl ceramide d18:1(4E)/24:0, and several endogenous
      lipids present within a porcine brain total lipid extract. In addition to the
      product ions formed by higher energy collision dissociation (HCD), UVPD is shown
      to yield a series of novel structurally diagnostic product ions resulting from
      cleavage of both sphingosine carbon-carbon and acyl chain carbon-carbon double
      bonds for direct localization of site(s) of unsaturation, as well as via
      diagnostic cleavages of the sphingosine backbone and N-C amide bond linkages.
      With activation timescales and dissociation efficiencies similar to those found
      in conventional MS/MS strategies, this approach is therefore a promising new tool
      in the arsenal of ion activation techniques toward providing complete structural
      elucidation in automated, high-throughput lipid analysis workflows. Graphical
      Abstract ?.

PMID- 28455689
TI  - Aggregation and Adhesion Activity of Lactobacilli Isolated from Fermented
      Products In Vitro and In Vivo: a Potential Probiotic Strain.
AB  - Approximately 25 strains of lactobacilli isolated from different dairy products
      and fermented vegetables were screened according to their possibility to show the
      high auto-aggregation and co-aggregation. The strains Lactobacillus helveticus
      INRA-2010-H11, Lactobacillus rhamnosus INA-5.1, and Lactobacillus acidophilus JM
      2012 were determined to have the high auto-aggregation (approximately 73, 46, and
      70.5% correspondingly). A high co-aggregation capacity (75.53%) for strains INRA
      2010-H11 and JM-2012 was shown. The adhesion degree of INRA-2010-H11 on the
      surface of buccal epithelial cells was 88.23%. The study of INRA-2010-H11, JM
      2012, and both strains' mixture (1:1) adhesion capacity on the surface of
      epithelial HeLa cells revealed the adhesion of 1.1 * 106, 6.3 * 104, and 2.3 *
      105 CFU, respectively, from starter amount of CFU 107 and 108 for both strains.
      In vivo experiments of LAB adhesion in gastrointestinal tract of mouse revealed
      the presence of 2.5 * 109, 1.2 * 109, and 1.5 * 109 CFU of LAB in control and
      groups of mouse, fed by INRA-2010-H11 and mixture, respectively. Feeding by
      investigated lactobacilli was suggested to lead to microbiota biodiversity
      reduction in small intestine and colon and its augmentation in stomach. Thus,
      INRA-2010-H11 demonstrated a high aggregation and adhesion activity so it has the
      potential as a good probiotic strain.

PMID- 28455690
TI  - Comparative Growth Behaviour and Biofunctionality of Lactic Acid Bacteria During
      Fermentation of Soy Milk and Bovine Milk.
AB  - The study reports the growth, acidification and proteolysis of eight selected
      lactic acid bacteria in skim and soy milk. Angiotensin-converting enzyme
      inhibition and antimicrobial profiles of skim and soy milk fermented by the
      lactic acid bacteria were also determined. Among eight lactic cultures (S.
      thermophilus MD2, L. helveticus V3, L. rhamnosus NS6, L. rhamnosus NS4, L.
      bulgaricus NCDC 09, L. acidophilus NCDC 15, L. acidophilus NCDC 298 and L.
      helveticus NCDC 292) studied, L. bulgaricus NCDC 09 and S. thermophilus MD2
      decreased the pH of skim and soy milk in greater extent. Acid production (i.e.
      titratable acidity) by L. bulgaricus NCDC 09 and L. helveticus V3 was higher than
      other strains. Higher viable counts were observed in S. thermophilus MD2 and L.
      helveticus V3. Higher proteolysis was exhibited by S. thermophilus MD2 and L.
      rhamnosus NS6 in both skim and soy milk. Milk fermented by S. thermophilus (MD2)
      exhibited highest angiotensin-converting enzyme inhibition. Antimicrobial
      activities of cell-free supernatant of milk fermented by S. thermophilus MD2 and
      L. helveticus V3 were higher. All the tested lactic acid bacteria performed
      better in skim milk as compared to soy milk.

PMID- 28455691
TI  - Long-Lasting Cerebral Vasospasm, Microthrombosis, Apoptosis and Paravascular
      Alterations Associated with Neurological Deficits in a Mouse Model of
      Subarachnoid Hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality and
      morbidity. Long-term cognitive and sensorimotor deficits are serious
      complications following SAH but still not well explained and described in mouse
      preclinical models. The aim of our study is to characterize a well-mastered SAH
      murine model and to establish developing pathological mechanisms leading to
      cognitive and motor deficits, allowing identification of specific targets
      involved in these long-term troubles. We hereby demonstrate that the double blood
      injection model of SAH induced long-lasting large cerebral artery vasospasm
      (CVS), microthrombosis formation and cerebral brain damage including defect in
      potential paravascular diffusion. These neurobiological alterations appear to be
      associated with sensorimotor and cognitive dysfunctions mainly detected 10 days
      after the bleeding episode. In conclusion, this characterized model of SAH in
      mice, stressing prolonged neurobiological pathological mechanisms and associated
      sensitivomotor deficits, will constitute a validated preclinical model to better
      decipher the link between CVS, long-term cerebral apoptosis and cognitive
      disorders occurring during SAH and to allow investigating novel therapeutic
      approaches in transgenic mice.

PMID- 28455692
TI  - Transependymal Cerebrospinal Fluid Flow: Opportunity for Drug Delivery?
AB  - Drug delivery to the central nervous system (CNS) is complicated by the blood
      brain barrier. As a result, many agents that are found to be potentially
      effective at their site of action cannot be sufficiently or effectively delivered
      to the CNS and therefore have been discarded and not developed further for
      clinical use, leaving many CNS diseases untreated. One way to overcome this
      obstacle is intracerebroventricular (ICV) delivery of the therapeutics directly
      to cerebrospinal fluid (CSF). Recent experimental and clinical findings reveal
      that CSF flows from the ventricles throughout the parenchyma towards the
      subarachnoid space also named minor CSF pathway, while earlier, it was suggested
      that only in pathological conditions such as hydrocephalus this form of CSF flow
      occurs. This transependymal flow of CSF provides a route to distribute ICV
      infused drugs throughout the brain. More insight on transependymal CSF flow will
      direct more rational to ICV drug delivery and broaden its clinical indications in
      managing CNS diseases.

PMID- 28455694
TI  - Increased Root Canal Endotoxin Levels are Associated with Chronic Apical
      Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression,
      Severity of Depression, and a Lowered Quality of Life.
AB  - Evidence indicates that major depression is accompanied by increased
      translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent
      activation of oxidative and nitrosative (O&NS) pathways. This present study
      examined the associations among chronic apical periodontitis (CAP), root canal
      endotoxin levels (lipopolysaccharides, LPS), O&NS pathways, depressive symptoms,
      and quality of life. Measurements included advanced oxidation protein products
      (AOPP), nitric oxide metabolites (NOx), lipid peroxides (LOOH), -sulfhydryl (SH)
      groups, total radical trapping antioxidant parameter (TRAP), and paraoxonase
      (PON)1 activity in participants with CAP, with and without depression, as well as
      healthy controls (no depression, no CAP). Root canal LPS levels were positively
      associated with CAP, clinical depression, severity of depression (as measured
      with the Hamilton Depression Rating Scale (HDRS) and the Beck Depression
      Inventory) and O&NS biomarkers, especially NOx and TRAP. CAP-related depression
      was accompanied by increased levels of NOx, LOOH, AOPP, and TRAP. In CAP
      participants, there was a strong correlation (r = 0.734, p < 0.001) between root
      canal LPS and the HDRS score. There were significant and positive associations
      between CAP or root canal endotoxin with the vegetative and physio-somatic
      symptoms of the HDRS as well as a significant inverse association between root
      canal endotoxin and quality of life with strong effects on psychological,
      environmental, and social domains. It is concluded that increased root canal LPS
      accompanying CAP may cause depression and a lowered quality of life, which may be
      partly explained by activated O&NS pathways, especially NOx thereby enhancing
      hypernitrosylation and thus neuroprogressive processes. Dental health and "leaky
      teeth" may be intimately linked to the etiology and course of depression, while
      significantly impacting quality of life.

PMID- 28455693
TI  - Therapeutic Strategies Under Development Targeting Inflammatory Mechanisms in
      Amyotrophic Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by
      the progressive loss of cortical, bulbar, and spinal motor neurons (MNs). The
      cardinal manifestation of ALS is a progressive paralysis which leads to death
      within a time span of 3 to 5 years after disease onset. Despite similar final
      output of neuronal death, the underlying pathogenic causes are various and no
      common cause of neuronal damage has been identified to date. Inflammation
      mediated neuronal injury is increasingly recognized as a major factor that
      promotes disease progression and amplifies the MN death-inducing processes. The
      neuroimmune activation is not only a physiological reaction to cell-autonomous
      death but is an active component of nonautonomous cell death. Such injury
      perpetuating phenomenon is now proved to be a common mechanism in many human
      disorders characterized by progressive neurodegeneration. Therefore, it
      represents an interesting therapeutic target. To date, no single cell population
      has been proved to play a major role. The existing evidence points to a complex
      cross talk between resident immune cells and nonresident cells, like monocytes
      and T lymphocytes, and to a dysregulation in cytokine profile and in phenotype
      commitment. After a summary of the most important mechanisms involved in the
      inflammatory reaction in ALS, this review will focus on novel therapeutic tools
      that rely on tackling inflammation to improve motor function and survival.
      Herein, completed, ongoing, or planned clinical trials, which aim to modify the
      rapidly fatal course of this disease, are discussed. Anti-inflammatory compounds
      that are currently undergoing preclinical study and novel suitable molecular
      targets are also mentioned.

PMID- 28455695
TI  - PKA-GSK3beta and beta-Catenin Signaling Play a Critical Role in Trans-Resveratrol
      Mediated Neuronal Differentiation in Human Cord Blood Stem Cells.
AB  - The role of resveratrol (RV), a natural polyphenol, is well documented, although
      its role on neurogenesis is still controversial and poorly understood. Therefore,
      to decipher the cellular insights of RV on neurogenesis, we investigated the
      potential effects of the compound on the survival, proliferation, and neuronal
      differentiation of human cord blood-derived mesenchymal stem cells (hCBMSCs). For
      neuronal differentiation, purified and characterized hCBMSCs were exposed to
      biological safe doses of RV (10 MUM) alone and in combination with nerve growth
      factor (NGF-50 ng). The cells exposed only to NGF (50 ng/mL) served as positive
      control for neuronal differentiation. The genes showing significant involvement
      in the process of neuronal differentiation were further funneled down at
      transcriptional and translational level. It was observed that RV promotes PKA
      mediated neuronal differentiation in hCBMSCs by inducing canonical pathway. The
      studies with pharmacological inhibitors also confirmed that PKA significantly
      induces beta-catenin expression via GSK3beta induction and stimulates CREB
      phosphorylation and pERK1/2 induction. Besides that, the studies also revealed
      that RV additionally possesses the binding sites for molecules other than PKA and
      GSK3beta, with which it interacts. The present study therefore highlights the
      positive impact of RV over the survival, proliferation, and neuronal
      differentiation in hCBMSCs via PKA-mediated induction of GSK3beta, beta catenin,
      CREB, and ERK1/2.

PMID- 28455696
TI  - Viruses and Multiple Sclerosis: From Mechanisms and Pathways to Translational
      Research Opportunities.
AB  - Viruses are directly or indirectly implicated in multiple sclerosis (MS). Here,
      we review the evidence on the virus-related pathophysiology of MS, introduce
      common experimental models, and explore the ways in which viruses cause
      demyelination. By emphasizing knowledge gaps, we highlight future research
      directions for effective MS diagnostics and therapies: (i) identifying biomarkers
      for at-risk individuals, (ii) searching for direct evidence of specific causative
      viruses, (iii) establishing the contribution of host genetic factors and viruses,
      and (iv) investigating the contribution of immune regulation at extra-CNS sites.
      Research in these areas is likely to be facilitated by the application of high
      throughput technologies, the development of systems-based bioinformatic
      approaches, careful selection of experimental models, and the acquisition of high
      quality clinical material for tissue-based research.

PMID- 28455697
TI  - The Differentiation of Skin Mesenchymal Stem Cells Towards a Schwann Cell
      Phenotype: Impact of Sigma-1 Receptor Activation.
AB  - Neural crest stem cells (NCSCs) are the source of mature Schwann cells in the
      peripheral nervous system (PNS). The NCSC population resides in the bulge of hair
      follicles and in the dermis. Recently, it was shown that 2-3% of the human dermis
      mesenchymal stem cell (MSC) population expresses the NCSC marker CD271, thus
      enabling the use of skin MSCs for studying Schwann cell differentiation in vitro.
      The aims of this study were to establish a protocol for human skin MSC
      differentiation towards Schwann cell-like cells (SC-lcs) and to analyse the
      expression of sigma-1 receptor (S1R) in SC-lcs. The impact of S1R ligands, namely
      the selective agonist PRE-084, the positive allosteric modulator E1R and the
      selective antagonist NE-100, on Schwann cell differentiation was assessed. The
      expression of the neuron-specific genes Tubulin-betaIII and Integrin-6alpha, the
      Schwann cell-specific gene S100b, MBP and the NCSC-specific genes p75NTR, Sox10,
      Notch1, Integrin-4alpha, Ap2alpha and Pax6 was analysed in MSCs and SC-lcs by
      real-time RT-PCR. BDNF secretion was evaluated by ELISA. The effect of S1R
      ligands on SC-lc differentiation was measured using BDNF ELISA and MBP flow
      cytometry. After MSC differentiation, NCSC markers p75NTR and Integrin-4alpha
      were downregulated 3.5-fold and 2-fold, respectively. To the contrary, MBP and
      S100b were significantly upregulated in SC-lcs. S1R ligands showed a tendency to
      increase the secretion of BDNF by the SC-lc population. PRE-084 and E1R increased
      MBP expression in the SC-lc population, whereas 3 MUM NE-100 inhibited MBP
      expression in SC-lcs. In conclusion, our data demonstrate that S1R plays an
      important role in skin MSC differentiation towards myelinating Schwann cells.

PMID- 28455698
TI  - TMEM230 Mutations Are Rare in Han Chinese Patients with Autosomal Dominant
      Parkinson's Disease.
AB  - Mutations in the gene encoding the transmembrane protein 230 (TMEM230) have been
      reported in patients with familial, autosomal dominant inherited Parkinson's
      disease (ADPD). The aim of the present study was to explore the role and the
      prevalence of TMEM230 mutations in Chinese patients with ADPD. A cohort of 120
      patients with ADPD and 650 healthy controls (HCs) from the Department of
      Neurology, West China Hospital of Sichuan University was screened. The entire
      coding exons of TREM230 in all the patients, as well as exon 5 of this gene in
      the 650 HCs, were directly sequenced with the Sanger sequencing approach. Novel
      identified mutations or variants of Parkinson's disease were tested in all HCs in
      the corresponding chromosomal regions. Two novel variants of the TMEM230 gene
      were identified. The c.46G>T [p. Gly16Trp] variant in exon 1 was identified in a
      male PD patient, while a heterozygous frameshift variant, c.429delT [p.
      Val143ValfsX4], in exon 5 was found in an HC. However, the most commonly reported
      mutation, p.*184ProGlyext*5, was not detected in either the patients or control
      subjects in this study. Our findings suggested that TMEM230 mutations are very
      rare in the ADPD Han Chinese population. Further evaluation of genetic data from
      a larger sample population is required to understand the genetic role of TMEM230
      in the etiology of PD.

PMID- 28455699
TI  - An In Vivo 11C-(R)-PK11195 PET and In Vitro Pathology Study of Microglia
      Activation in Creutzfeldt-Jakob Disease.
AB  - Microgliosis is part of the immunobiology of Creutzfeldt-Jakob disease (CJD).
      This is the first report using 11C-(R)-PK11195 PET imaging in vivo to measure 18
      kDa translocator protein (TSPO) expression, indexing microglia activation, in
      symptomatic CJD patients, followed by a postmortem neuropathology comparison. One
      genetic CJD (gCJD) patient, two sporadic CJD (sCJD) patients, one variant CJD
      (vCJD) patient (mean +/- SD age, 47.50 +/- 15.95 years), and nine healthy
      controls (mean +/- SD age, 44.00 +/- 11.10 years) were included in the study.
      TSPO binding potentials were estimated using clustering and parametric analyses
      of reference regions. Statistical comparisons were run at the regional and at the
      voxel-wise levels. Postmortem evaluation measured scrapie prion protein (PrPSc)
      immunoreactivity, neuronal loss, spongiosis, astrogliosis, and microgliosis. 11C
      (R)-PK11195-PET showed a significant TSPO overexpression at the cortical level in
      the two sCJD patients, as well as thalamic and cerebellar involvement; very
      limited parieto-occipital activation in the gCJD case; and significant increases
      at the subcortical level in the thalamus, basal ganglia, and midbrain and in the
      cerebellum in the vCJD brain. Along with misfolded prion deposits, neuropathology
      in all patients revealed neuronal loss, spongiosis and astrogliosis, and a
      diffuse cerebral and cerebellar microgliosis which was particularly dense in
      thalamic and basal ganglia structures in the vCJD brain. These findings confirm
      significant microgliosis in CJD, which was variably modulated in vivo and more
      diffuse at postmortem evaluation. Thus, TSPO overexpression in microglia
      activation, topography, and extent can vary in CJD subtypes, as shown in vivo,
      possibly related to the response to fast apoptotic processes, but reaches a large
      amount at the final disease course.

PMID- 28455700
TI  - Short-Term Fructose Feeding Induces Inflammation and Oxidative Stress in the
      Hippocampus of Young and Adult Rats.
AB  - The drastic increase in the consumption of fructose encouraged the research to
      focus on its effects on brain physio-pathology. Although young and adults differ
      largely by their metabolic and physiological profiles, most of the previous
      studies investigated brain disturbances induced by long-term fructose feeding in
      adults. Therefore, we investigated whether a short-term consumption of fructose
      (2 weeks) produces early increase in specific markers of inflammation and
      oxidative stress in the hippocampus of young and adult rats. After the high
      fructose diet, plasma lipopolysaccharide and tumour necrosis factor (TNF)-alpha
      were found significantly increased in parallel with hippocampus inflammation,
      evidenced by a significant rise in TNF-alpha and glial fibrillar acidic protein
      concentrations in both the young and adult groups. The fructose-induced
      inflammatory condition was associated with brain oxidative stress, as increased
      levels of lipid peroxidation and nitro-tyrosine were detected in the hippocampus.
      The degree of activation of the protein kinase B, extracellular signal-regulated
      kinase 1/2, and insulin receptor substrate 1 pathways found in the hippocampus
      after fructose feeding indicates that the detrimental effects of the fructose
      rich diet might largely depend on age. Mitochondrial function in the hippocampus,
      together with peroxisome proliferator-activated receptor gamma coactivator 1
      alpha content, was found significantly decreased in fructose-treated adult rats.
      In vitro studies with BV-2 microglial cells confirmed that fructose treatment
      induces TNF-alpha production as well as oxidative stress. In conclusion, these
      results suggest that unbalanced diet, rich in fructose, may be highly deleterious
      in young people as in adults and must be strongly discouraged for the prevention
      of diet-associated neuroinflammation and neurological diseases.

PMID- 28455701
TI  - Chronic REM Sleep Restriction in Juvenile Male Rats Induces Anxiety-Like Behavior
      and Alters Monoamine Systems in the Amygdala and Hippocampus.
AB  - Adolescence is marked by major physiological changes, including those in the
      sleep-wake cycle, such as phase delay, which may result in reduced sleep hours.
      Sleep restriction and/or deprivation in adult rats activate stress response and
      seem to be a risk factor for triggering emotional disorders. In the present
      study, we sought to evaluate the behavioral and neurobiological consequences of
      prolonged REM sleep restriction in juvenile male rats. Immediately after weaning,
      on postnatal day 21, three males from each litter were submitted to REM sleep
      deprivation and the other three animals were maintained in their home-cages. REM
      sleep restriction (REMSR) was accomplished by placing the animals in the modified
      multiple platform method for 18 h and 6 h in the home-cage, where they could
      sleep freely; the sleep restriction lasted 21 consecutive days, during which all
      animals were measured and weighed every 3 days. After the end of this period, all
      animals were allowed to sleep freely for 2 days, and then the behavioral tests
      were performed for evaluation of depressive and anxiety-like profiles (sucrose
      negative contrast test and elevated plus maze, EPM). Blood sampling was performed
      5 min before and 30 and 60 min after the EPM for determination of corticosterone
      plasma levels. The adrenals were weighed and brains collected and dissected for
      monoamine levels and receptor protein expression. REMSR impaired the physical
      development of adolescents, persisting for a further week. Animals submitted to
      REMSR exhibited higher basal corticosterone levels and a greater anxiety index in
      the EPM, characteristic of an anxious profile. These animals also exhibited
      higher noradrenaline levels in the amygdala and ventral hippocampus, without any
      change in the expression of beta1-adrenergic receptors, as well as higher
      serotonin and reduced turnover in the dorsal hippocampus, with diminished
      expression of 5-HT1A. Finally, greater concentration of BDNF was observed in the
      dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during
      puberty impaired physical development and induced anxiety-like behavior,
      attributed to increased noradrenaline and serotonin levels in the amygdala and
      hippocampus.

PMID- 28455704
TI  - Development and Functional Differentiation of Tissue-Resident Versus Monocyte
      Derived Macrophages in Inflammatory Reactions.
AB  - Mononuclear phagocytes are key cells in tissue integrity and defense. Tissue
      resident macrophages are abundantly present in all tissues of the body and have a
      complex role in ensuring tissue functions and homeostatic balance. Circulating
      blood monocytes can enter tissue both in steady-state conditions, for helping in
      replenishing the tissue-resident macrophage pool and, in particular, for acting
      as potent effector cells during inflammatory events such as infections, traumas,
      and diseases. The heterogeneity of monocytes and macrophages depends on their
      ontogeny, their tissue location, and their functional programming, with both
      monocytes and macrophages able to exert distinct or similar functions depending
      on the tissue-specific and stimulus-specific microenvironment. In this short
      review, we will review the current hypotheses on tissue-resident macrophage
      ontogeny and functions, as compared to blood-derived monocytes, with a particular
      focus on inflammatory conditions.

PMID- 28455702
TI  - Allosteric Inhibition of Serotonin 5-HT7 Receptors by Zinc Ions.
AB  - The allosteric regulation of G protein-coupled receptors (GPCRs) is a well-known
      phenomenon, but there are only a few examples of allosteric modulation within the
      metabotropic serotonergic receptor family. Recently, we described zinc non
      competitive interactions toward agonist binding at serotonin 5-HT1A receptors, in
      which biphasic effects, involving potentiation at sub-micromolar concentrations
      (10 MUM) and inhibition at sub-millimolar concentrations (500 MUM) of Zn2+ in
      radioligand binding assays, were consistent with both the agonist and antagonist
      like effects of zinc ions observed in in vivo studies. Here, we showed new data
      demonstrating zinc allosteric inhibition of both agonist and antagonist binding
      at human recombinant 5-HT7 receptors stably expressed in HEK293 cells as observed
      by radioligand binding studies as well as zinc neutral antagonism displayed by
      the concentration of 10 MUM in the functional LANCE assay. The allosteric nature
      of the effect of Zn on 5-HT7 receptors was confirmed (1) in saturation studies in
      which zinc inhibited the binding of potent orthosteric 5-HT7 receptor
      radioligands, the agonist [3H]5-CT, and the two antagonists [3H]SB-269970 and
      [3H]mesulergine, showing ceiling effect and differences in the magnitude of
      negative cooperativity (alpha = 0.15, 0.06, and 0.25, respectively); (2) in
      competition experiments in which 500 MUM of zinc inhibited all radioligand
      displacements by non-labeled orthosteric ligands (5-CT, SB-269970, and
      clozapine), and the most significant reduction in affinity was observed for the 5
      CT agonist (4.9-16.7-fold) compared with both antagonists (1.4-3.9-fold); and (3)
      in kinetic experiments in which 500 MUM zinc increased the dissociation rate
      constants for [3H]5-CT and [3H]mesulergine but not for [3H]SB-269970.
      Additionally, in the functional LANCE test using the constitutively active HEK293
      cell line expressing the 5-HT7 receptor, 10 MUM zinc had features of neutral
      antagonism and increased the EC50 value of the 5-CT agonist by a factor of 3.2.
      Overall, these results showed that zinc can act as a negative allosteric
      inhibitor of 5-HT7 receptors. Given that the inhibiting effects of low
      concentrations of zinc in the functional assay represent the most likely
      direction of zinc activity under physiological conditions, among numerous zinc
      regulated proteins, the 5-HT7 receptor can be considered a serotonergic target
      for zinc modulation in the CNS.

PMID- 28455705
TI  - Hofbauer Cells: Placental Macrophages of Fetal Origin.
AB  - Pregnancy complications such as preterm birth, miscarriage, maternal and/or
      neonatal morbidities, and mortality can be manifestations of underlying placental
      pathology. Hofbauer cells refer to a heterogeneous population of fetal
      macrophages that reside within the functional unit of the placenta known as the
      chorionic villus. Hofbauer cells can be detected within the connective tissue
      matrix of the placenta as early as 4 weeks post-conception and are present
      throughout pregnancy. These cells are implicated in a wide array of functions
      important for a successful pregnancy including placental morphogenesis, immune
      regulation, control of stromal water content, and the transfer of ions and serum
      proteins across the maternal-fetal barrier. Derangements in Hofbauer cell
      homeostasis are associated with placental pathologies involving infection,
      inflammation, and inadequate placental development. Despite a growing body of
      evidence that these cells are important, our knowledge about Hofbauer cell
      function in both normal and dysfunctional pregnancy is rudimentary. The goal of
      this chapter is to provide an overview of what is known about Hofbauer cell
      origins and their potential roles in normal and complicated pregnancy. We also
      review established and emerging methodologies available for the study of Hofbauer
      cells during in vitro and in vivo conditions.

PMID- 28455703
TI  - Evolutionary Aspects of Macrophages Polarization.
AB  - Macrophages constitute a heterogeneous population of myeloid cells that are
      essential for maintaining homeostasis and as a first line of innate responders
      controlling and organizing host defenses against pathogens. Monocyte-macrophage
      lineage cells are among the most functionally diverse and plastic cells of the
      immune system. They undergo specific activation into functionally distinct
      phenotypes in response to immune signals and microbial products. In mammals,
      macrophage functional heterogeneity is defined by two activation states, M1 and
      M2, which represent two polar ends of a continuum exhibiting pro-inflammatory and
      tissue repair activities, respectively. While the ancient evolutionary origin of
      macrophages as phagocytic defenders is well established, the evolutionary roots
      of the specialized division of macrophages into subsets with polarized activation
      phenotypes is less well defined. Accordingly, this chapter focuses on recent
      advances in the understanding of the evolution of macrophage polarization and
      functional heterogeneity with a focus on ectothermic vertebrates.

PMID- 28455706
TI  - Mesenchymal Stem Cells Direct the Immunological Fate of Macrophages.
AB  - Mesenchymal stem cells (MSC) are multipotent stem cells with a broad well
      described immunosuppressive potential. They are able to modulate both the innate
      and the adaptive immune response. Particularly, MSC are able to regulate the
      phenotype and function of macrophages that are critical for different biological
      processes including wound healing, inflammation, pathogenesis of several
      autoimmune diseases, and tumor growth. These multifunctional roles of macrophages
      are due to their high plasticity, which enable them to adopt different phenotypes
      such as a pro-inflammatory M1 and anti-inflammatory M2 phenotype. MSC promote
      macrophage differentiation toward an M2-like phenotype with a high tissue
      remodeling potential and anti-inflammatory activity but also a pro-tumorigenic
      function. MSC regulatory effect on macrophages is mediated through the secretion
      of different immunomodulatory molecules such as PGE2, IL1RA, and IL-6. Moreover,
      the presence of macrophages in damaged tissue and inflammation is essential for
      MSC to exert their therapeutic function. In this chapter, we discuss how the
      interplay between macrophages and MSC mutually modulates their phenotypes and
      functions, orchestrates tissue repair, and controls inflammation during
      autoimmunity and tumor growth.

PMID- 28455707
TI  - Monocyte/Macrophage: NK Cell Cooperation-Old Tools for New Functions.
AB  - Monocyte/macrophage and natural killer (NK) cells are partners from a
      phylogenetic standpoint of innate immune system development and its evolutionary
      progressive interaction with adaptive immunity. The equally conservative ways of
      development and differentiation of both invertebrate hemocytes and vertebrate
      macrophages are reviewed. Evolutionary conserved molecules occurring in
      macrophage receptors and effectors have been inherited by vertebrates after their
      common ancestor with invertebrates. Cytolytic functions of mammalian NK cells,
      which are rooted in immune cells of invertebrates, although certain NK cell
      receptors (NKRs) are mammalian new events, are characterized. Broad heterogeneity
      of macrophage and NK cell phenotypes that depends on surrounding microenvironment
      conditions and expression profiles of specific receptors and activation
      mechanisms of both cell types are discussed. The particular tissue specificity of
      macrophages and NK cells, as well as their plasticity and mechanisms of their
      polarization to different functional subtypes have been underlined. The chapter
      summarized studies revealing the specific molecular mechanisms and regulation of
      NK cells and macrophages that enable their highly specific cross-cooperation.
      Attention is given to the evolving role of human monocyte/macrophage and NK cell
      interaction in pathogenesis of hypersensitivity reaction-based disorders,
      including autoimmunity, as well as in cancer surveillance and progression.

PMID- 28455708
TI  - Macrophages in Invertebrates: From Insects and Crustaceans to Marine Bivalves.
AB  - Macrophages are critical components of the antimicrobial response. The recent
      explosion of knowledge on the evolutionary, genetic, and biochemical aspects of
      the interaction between macrophages and microbes has renewed scientific interest
      in macrophages. The conservation of immune components or mechanisms between
      organisms during the evolutionary process allows us to elucidate antimicrobial
      mechanisms or discover new immune functions through the study of basal-branching
      organisms, such as invertebrates. As a result, immunity in non-vertebrates has
      attracted the attention of researchers in the last few decades. In this review,
      we summarize what is presently known about macrophage-like cells in various
      invertebrate species.

PMID- 28455709
TI  - F4/80 as a Major Macrophage Marker: The Case of the Peritoneum and Spleen.
AB  - Tissue macrophages are a heterogeneous cell population residing in all body
      tissues that contribute to the maintenance of homeostasis and trigger immune
      activation in response to injurious stimuli. This heterogeneity may be associated
      with tissue-specific functions; however, the presence of distinct macrophage
      populations within the same microenvironment indicates that macrophage
      heterogeneity may also be influenced outside of tissue specialization. The F4/80
      molecule was established as a unique marker of murine macrophages when a
      monoclonal antibody was found to recognize an antigen exclusively expressed by
      these cells. However, recent research has shown that F4/80 is expressed by other
      immune cells and is not equivalently expressed across tissue-specific macrophage
      lineages, including those residing in the same microenvironment, such as the
      peritoneum and spleen. In this context, two murine macrophage subtypes with
      distinct F4/80 expression patterns were recently found to coexist in the
      peritoneum, termed large peritoneal macrophages (LPMs) and small peritoneal
      macrophages (SPMs). However, the presence of phenotypic and functional
      heterogeneous macrophage subpopulations in the spleen was already known. Thus,
      although F4/80 surface expression continues to be the best method to identify
      tissue macrophages, additional molecules must also be examined to distinguish
      these cells from other immune cells.

PMID- 28455710
TI  - Immunobiology of Nitric Oxide and Regulation of Inducible Nitric Oxide Synthase.
AB  - Nitric oxide (NO) is a bioactive gas that has multiple roles in innate and
      adaptive immune responses. In macrophages, nitric oxide is produced by inducible
      nitric oxide synthase upon microbial and cytokine stimulation. It is needed for
      host defense against pathogens and for immune regulation. This review will
      summarize the role of NO and iNOS in inflammatory and immune responses and will
      discuss the regulatory mechanisms that control inducible nitric oxide synthase
      expression and activity.

PMID- 28455711
TI  - Role for Mechanotransduction in Macrophage and Dendritic Cell Immunobiology.
AB  - Tissue homeostasis is not only controlled by biochemical signals but also through
      mechanical forces that act on cells. Yet, while it has long been known that
      biochemical signals have profound effects on cell biology, the importance of
      mechanical forces has only been recognized much more recently. The types of
      mechanical stress that cells experience include stretch, compression, and shear
      stress, which are mainly induced by the extracellular matrix, cell-cell contacts,
      and fluid flow. Importantly, macroscale tissue deformation through stretch or
      compression also affects cellular function.Immune cells such as macrophages and
      dendritic cells are present in almost all peripheral tissues, and monocytes
      populate the vasculature throughout the body. These cells are unique in the sense
      that they are subject to a large variety of different mechanical environments,
      and it is therefore not surprising that key immune effector functions are altered
      by mechanical stimuli. In this chapter, we describe the different types of
      mechanical signals that cells encounter within the body and review the current
      knowledge on the role of mechanical signals in regulating macrophage, monocyte,
      and dendritic cell function.

PMID- 28455712
TI  - Macrophages' Role in Tissue Disease and Regeneration.
AB  - Inflammation is an essential component of the normal mammalian host tissue
      response and plays an important role during cardiovascular and musculoskeletal
      diseases. Given the important role of inflammation on the host tissue response
      after injury, understanding this process represents essential aspects of
      biomedical research, tissue engineering, and regenerative medicine. Macrophages
      are central players during the inflammatory response with an extensive role
      during wound healing. These cells exhibit a spectrum of activation states that
      span from pro-inflammatory to pro-healing phenotypes. The phenotype of the
      macrophages can have profound influences on the progression of disease or injury.
      As such, understanding and subsequent modulation of macrophage phenotype
      represents an exciting target area for regenerative medicine therapies. In this
      chapter, we describe the role of macrophages in specific cases of injury and
      disease. After myocardial infarction, a biphasic response of pro- and anti
      inflammatory macrophages are involved in the remodeling process. In volumetric
      muscle loss, there is an intricate communication between inflammatory cells and
      progenitor cells affecting repair processes. Osteoarthritis is characterized by
      increased levels of pro-inflammatory macrophages over an extended period of time
      with significant impact on the progression of the disease. By harnessing the
      complex role of macrophages, enhanced therapeutic treatments can be developed
      that enhance the normal healing response as well as help the survival of
      therapeutic cells delivered to the site of injury.

PMID- 28455713
TI  - Macrophages and Their Contribution to the Development of Atherosclerosis.
AB  - Atherosclerosis can be regarded as chronic inflammatory disease driven by lipid
      accumulation in the arterial wall. Macrophages play a key role in the development
      of local inflammatory response and atherosclerotic lesion growth. Atherosclerotic
      plaque is a complex microenvironment, in which different subsets of macrophages
      coexist executing distinct, although in some cases overlapping functions.
      According to the classical simplified nomenclature, lesion macrophages can belong
      to pro-inflammatory or anti-inflammatory or alternatively activated types. While
      the former promote the inflammatory response and participate in lipid
      accumulation, the latter are responsible for the inflammation resolution and
      plaque stabilisation. Atherosclerotic lesion dynamics depends therefore on the
      balance between these macrophages populations. The diverse functions of
      macrophages make them an attractive therapeutic target for the development of
      novel anti-atherosclerotic treatments. In this chapter, we discuss different
      types of macrophages and their roles in atherosclerotic lesion dynamics and
      describe the results of several experiments studying macrophage polarisation in
      atherosclerosis.

PMID- 28455714
TI  - Macrophage Dysfunction in Respiratory Disease.
AB  - In the healthy lung, macrophages maintain homeostasis by clearing inhaled
      particles, bacteria, and removing apoptotic cells from the local pulmonary
      environment. However, in respiratory diseases including chronic obstructive
      pulmonary disease (COPD), asthma, and cystic fibrosis, macrophages appear to be
      dysfunctional and may contribute to disease pathogenesis. In COPD, phagocytosis
      of bacterial species and apoptotic cells by both alveolar macrophages and
      monocyte-derived macrophages is significantly reduced, leading to colonization of
      the lung with pathogenic bacteria. COPD macrophages also release high levels of
      pro-inflammatory cytokines and chemokines, including CXCL8, TGFbeta, and CCL2,
      driving recruitment of other inflammatory cells including neutrophils and
      monocytes to the lungs and promoting disease progression.In asthma, defective
      phagocytosis and efferocytosis have also been reported, and macrophages appear to
      have altered cell surface receptor expression; however, it is as yet unclear how
      this contributes to disease progression but may be important in driving Th2
      mediated inflammation. In cystic fibrosis, macrophages also display defective
      phagocytosis, and reduced bacterial killing, which may be driven by the pro
      inflammatory environment present in the lungs of these patients.The mechanisms
      behind defective macrophage function in lung diseases are not currently
      understood, but potential mechanisms include alterations in phagocytic receptor
      expression levels, oxidative stress, but also the possibility that specific
      diseases are associated with a specific, altered, macrophage phenotype that
      displays reduced function. Identification of the mechanisms responsible may
      present novel therapeutic opportunities for treatment.

PMID- 28455715
TI  - Activation of Macrophages in Response to Biomaterials.
AB  - Macrophages are the initial biologic responders to biomaterials. These highly
      plastic immune sentinels control and modulate responses to materials, foreign or
      natural. The responses may vary from immune stimulatory to immune suppressive.
      Several parameters have been identified that influence macrophage response to
      biomaterials, specifically size, geometry, surface topography, hydrophobicity,
      surface chemistry, material mechanics, and protein adsorption. In this review,
      the influence of these parameters is supported with examples of both synthetic
      and naturally derived materials and illustrates that a combination of these
      parameters ultimately influences macrophage responses to the biomaterial. Having
      an understanding of these properties may lead to highly efficient design of
      biomaterials with desirable biologic response properties.

PMID- 28455716
TI  - Macrophage Differentiation in Normal and Accelerated Wound Healing.
AB  - Chronic wounds pose considerable public health challenges and burden. Wound
      healing is known to require the participation of macrophages, but mechanisms
      remain unclear. The M1 phenotype macrophages have a known scavenger function, but
      they also play multiple roles in tissue repair and regeneration when they
      transition to an M2 phenotype. Macrophage precursors (mononuclear
      cells/monocytes) follow the influx of PMN neutrophils into a wound during the
      natural wound-healing process, to become the major cells in the wound. Natural
      wound-healing process is a four-phase progression consisting of hemostasis,
      inflammation, proliferation, and remodeling. A lag phase of 3-6 days precedes the
      remodeling phase, which is characterized by fibroblast activation and finally
      collagen production. This normal wound-healing process can be accelerated by the
      intracellular delivery of ATP to wound tissue. This novel ATP-mediated
      acceleration arises due to an alternative activation of the M1 to M2 transition
      (macrophage polarization), a central and critical feature of the wound-healing
      process. This response is also characterized by an early increased release of pro
      inflammatory cytokines (TNF, IL-1 beta, IL-6), a chemokine (MCP-1), an activation
      of purinergic receptors (a family of plasma membrane receptors found in almost
      all mammalian cells), and an increased production of platelets and platelet
      microparticles. These factors trigger a massive influx of macrophages, as well as
      in situ proliferation of the resident macrophages and increased synthesis of
      VEGFs. These responses are followed, in turn, by rapid neovascularization and
      collagen production by the macrophages, resulting in wound covering with
      granulation tissue within 24 h.

PMID- 28455717
TI  - Macrophages and RhoA Pathway in Transplanted Organs.
AB  - RhoA is a small GTPase that, via its downstream effectors, regulates a variety of
      cell functions such as cytokinesis, cell migration, vesicular trafficking, and
      phagocytosis. As such the RhoA pathway is also pivotal for proper functioning of
      immune cells including macrophages. By controlling actin cytoskeleton
      organization, RhoA pathway modulates macrophage's polarity and basic functions:
      phagocytosis, migration, and extracellular matrix degradation. Numerous studies
      indicate that macrophages are very important effectors contributing to acute and
      chronic rejection of transplanted organs. In this review we discuss the role of
      RhoA pathway in governance of macrophage's functions in terms of transplanted
      organs.

PMID- 28455718
TI  - Time Trend Analysis of Hypertension Prevalence, Awareness, Treatment and Control
      in Italy: Novel Insights from Recent National Surveys in the General Population.

PMID- 28455719
TI  - Valgus slipped capital femoral epiphysis with contralateral pre-slip.
AB  - Slipped capital femoral epiphysis (SCFE) is a common hip disorder in older
      children and adolescents, classically with medial and posterior slippage of the
      proximal femoral epiphysis. However, valgus SCFE is a very rare entity, where the
      proximal femoral epiphysis slips laterally and posteriorly. To our knowledge,
      valgus SCFE with magnetic resonance imaging (MRI) features of contralateral pre
      slip has not yet been reported. We present a case of a 9 year old girl with
      symptomatic valgus SCFE on the left and asymptomatic contralateral pre-slip on
      the right with concurrent radiographic, sonographic, and MRI findings. Such
      findings include bilateral coxa valga, radiographic irregularity of the left
      proximal femoral physis, bilateral hip effusions, abnormal MRI signal and
      enhancement about both proximal femoral physes, and minimal posterolateral
      slippage of the left proximal femoral epiphysis. We highlight these pertinent
      imaging findings and review the importance of accurately diagnosing this rare
      entity for appropriate surgical management.

PMID- 28455720
TI  - Effect of different fermentation strategies on beta-mannanase production in fed
      batch bioreactor system.
AB  - Mannanases, one of the important enzyme group for industry, are produced by
      numerous filamentous fungi, especially Aspergillus species with different
      fermentation methods. The aim of this study was to show the best fermentation
      method of beta-mannanase production for fungal growth in fermenter. Therefore,
      different fermentation strategies in fed-batch fermentation (suspended,
      immobilized cell, biofilm and microparticle-enhanced bioreactor) were applied for
      beta-mannanase production from glucose medium (GM) and carob extract medium (CEM)
      by using recombinant Aspergillus sojae. The highest beta-mannanase activities
      were obtained from microparticle-enhanced bioreactor strategy. It was found to be
      347.47 U/mL by adding 10 g/L of Al2O3 to GM and 439.13 U/mL by adding 1 g/L of
      talcum into CEM. The maximum beta-mannanase activities for suspended,
      immobilization, and biofilm reactor remained at 72.55 U/mL in GM, 148.81 U/mL in
      CEM, and 194.09 U/mL in GM, respectively. The reason for that is the excessive,
      and irregular shaped growth and bulk formation, inadequate oxygen transfer or
      substrate diffusion in bioreactor. Consequently, the enzyme activity was
      significantly enhanced by addition of microparticles compared to other fed-batch
      fermentation strategies. Also, repeatable beta-mannanase activities were obtained
      by controlling of the cell morphology by adding microparticle inside the
      fermenter.

PMID- 28455722
TI  - Insufficient sleep is prevalent among migraineurs: a population-based study.
AB  - BACKGROUND: Sleep disorder and sleep complaints are common in subjects with
      migraine. Although the association between sleep disorders and migraine has been
      reported, the association between perceived insufficient sleep and migraine has
      rarely reported. The aim of this study is to evaluate the association between
      insufficient sleep and migraine using the data of the Korean Headache-Sleep Study
      (KHSS). METHODS: The KHSS is a nation-wide cross-sectional population-based
      survey regarding headache and sleep for Korean adults aged 19 to 69 years. A
      difference of one hour or more between sleep need and average sleep time
      indicated insufficient sleep. RESULTS: Of 2,695 participants, 727 (27.0%)
      individuals were classified as having insufficient sleep. The prevalence of
      insufficient sleep among individuals with migraine (45.5%) was significantly
      higher compared to that among individuals with non-migraine headache (32.9%, p =
      0.004) or among non-headache (20.4%, p < 0.001). Average sleep time did not
      differ among migraine, non-migraine headache, and non-headache groups (7.3 +/-
      1.2 vs. 7.2 +/- 1.2 vs. 7.3 +/- 1.4, p = 0.207). Multivariable logistic
      regression analyses demonstrated that migraine had an increased odds ratio (OR)
      for insufficient sleep after adjusting for sociodemographic variables, short
      sleep time, insomnia, poor sleep quality, anxiety, and depression (OR = 1.8, 95%
      confidence interval [CI] = 1. 2 - 2.7, p = 0.002). CONCLUSIONS: The prevalence of
      insufficient sleep was significantly higher among migraineurs compared to that in
      non-migraine headache or non-headache group.

PMID- 28455721
TI  - Broad Cognitive Profile in Children and Adolescents with HF-ASD and in Their
      Siblings: Widespread Underperformance and its Clinical and Adaptive Correlates.
AB  - Despite evidence supporting the presence of cognitive deficits in children and
      adolescents with high-functioning autism spectrum disorder (HF-ASD), the nature
      of these deficits and their clinical and adaptive correlates remain unclear.
      Moreover, there are few cognitive studies of ASD siblings as a high risk
      population. We compared 50 children and adolescents with HF-ASD, 22 unaffected
      siblings of the HF-ASD sample and 34 community controls using an extensive
      neuropsychological battery. Planning, cognitive flexibility, verbal and working
      memory, visual local-global processing and emotion recognition are impaired in HF
      ASD. Worse cognitive performance, especially in verbal and working memory, was
      significantly correlated with more severe symptoms and poorer adaptive
      functioning, also when controlling for intelligence quotient. Results in siblings
      may suggest an intermediate profile.

PMID- 28455723
TI  - Synthesis, localization and possible function of serine (or cysteine) peptidase
      inhibitor, clade B, member 6a (Serpinb6a) in mouse submandibular gland.
AB  - The granular convoluted tubule (GCT) in the duct system of the submandibular
      gland (SMG) develops preferentially in male mice and produces a number of
      bioactive peptides including proteases such as renin and kallikrein. We examine
      the synthesis and localization of the serine (or cysteine) peptidase inhibitor,
      clade B, member 6a (Serpinb6a), the mouse ortholog of the human intracellular
      serine protease inhibitor SERPINB6, in the mouse SMG by using reverse
      transcription plus the polymerase chain reaction, in situ hybridization,
      immunoblotting and immunohistochemistry. Serpinb6a mRNA expression was more
      abundant in the male than in the female SMG and in the GCT than in other duct
      portions or acini. Within GCT cells, immunoreactivity for Serpinb6a was localized
      in the nucleus and cytosol but was absent in the secretory granules. The binding
      target of Serpinb6a in the SMG was investigated by using a mass spectrometric
      analysis of immunoprecipitation products and kallikrein-1-related peptidase b26
      (Klk1b26), a serine protease, was identified. These results raise the possibility
      that Serpinb6a functions in the protection of GCT cells from intracellular
      kallikreins that may leak from secretory granules.

PMID- 28455724
TI  - Reevaluation of Pholiota squarrosa lectin-reactive haptoglobin as a pancreatic
      cancer biomarker using an improved ELISA system.
AB  - An increase in Lewis- and core-type fucosylation of haptoglobin has been reported
      in patients with pancreatic cancer (PC), suggesting that fucosylated haptoglobin
      is a candidate PC biomarker. Previously, we developed a Pholiota squarrosa lectin
      antibody enzyme-linked immunosorbent assay (PhoSL-ELISA) system for the detection
      of core-fucosylated haptoglobin. However, with this methodology, positive results
      were only obtained for some patients with PC, demonstrating the need for a more
      sensitive detection system. In the current study, we developed an improved PhoSL
      ELISA system with higher sensitivity to detect core-fucosylated haptoglobin using
      high-concentration urea as a denaturing agent with lectin to facilitate
      detection. We then reevaluated the performance of PhoSL reactive-core-fucosylated
      haptoglobin (PhoSL-HP) as a PC biomarker using the improved PhoSL-ELISA system.
      PhoSL-HP levels in the sera of patients with PC were significantly higher than
      those in healthy volunteers, with an area under the curve (AUC) value of 0.753.
      Furthermore, the AUC value of CA19-9 improved from 0.793 to 0.907 when combined
      with PhoSL-HP. Additionally, several CA19-9-negative cases among the patients
      with PC were diagnosed as positive for PhoSL-HP. In conclusion, PhoSL-HP
      detection using our improved ELISA system might allow PhoSL-HP to serve as a
      potential biomarker for PC and thus might be useful to complement the detection
      of CA19-9 in PC diagnosis.

PMID- 28455725
TI  - Can ultrasonography-guided aspiration and steroid injection treat reflux venous
      blood flow around symptomatic Baker's cysts? Our short-term experience.
AB  - OBJECTIVE: The aim of the current study was to investigate the efficacy of
      ultrasonography-guided aspiration treatment with concomitant steroid injection on
      relieving reflux blood flow in veins located next to symptomatic Baker's cyst.
      METHODS: All patients were examined by ultrasonography at administration and 1
      month follow-up after intervention. Puncture and aspiration of the cyst, as well
      as injection of 1 ml dexamethasone were performed by the same radiologist.
      Compression on popliteal vein and vena saphena parva and the degrees of reflux
      before and after treatment were recorded. RESULTS: Twenty-six patients were
      included in the study. An overall reduction of the cyst's size was observed in
      all patients of the study group. Reduction of the cyst size is more evident
      during the 1st week, which was observed by a slight enlargement during the 1st
      and the 3rd months controls. CONCLUSION: Ultrasonography-guided puncture,
      aspiration and steroid injection seems to yield promising outcomes in terms of
      relieving venous reflux flow around simple Baker's cysts.

PMID- 28455727
TI  - Perioperative considerations for patients with sickle cell disease: a narrative
      review.
AB  - PURPOSE: Approximately 200,000 individuals worldwide are born annually with
      sickle cell disease (SCD). Regions with the highest rates of SCD include Africa,
      the Mediterranean, and Asia, where its prevalence is estimated to be 2-6% of the
      population. An estimated 70,000-100,000 people in the United States have SCD. Due
      to enhanced newborn screening, a better understanding of this disease, and more
      aggressive therapy, many sickle cell patients survive into their adult years and
      present more frequently for surgery. SOURCE: The authors identified relevant
      medical literature by searching PubMed, MEDLINE(r), EMBASETM, ScopusTM, Web of
      Science, and Google Scholar databases for English language publications appearing
      from 1972-September 2016. Case reports, abstracts, review articles, and original
      research articles were reviewed-with particular focus on the pathophysiology and
      medical management of SCD and any anesthesia-related issues. PRINCIPAL FINDINGS:
      Perioperative physicians should be familiar with the triggers of a sickle cell
      crisis and vaso-occlusive disease. Sickle cell disease affects various organ
      systems, including the central nervous, cardiovascular, pulmonary, genitourinary,
      and musculoskeletal systems. Preoperative assessment should focus on end-organ
      dysfunction. Controversy continues regarding if and when sickle cell patients
      should receive transfusions and which anesthetic technique (regional or general)
      confers any benefits. Timely, appropriate, and sufficient analgesia is critical,
      especially when patients experience a vaso-occlusive crisis, acute chest
      syndrome, or acute postoperative pain. CONCLUSION: Effective management of SCD
      patients in the perioperative setting requires familiarity with the epidemiology,
      pathophysiology, clinical manifestations, and treatment of SCD.

PMID- 28455726
TI  - Developmental Expression of Claudins in the Mammary Gland.
AB  - Claudins are a large family of membrane proteins whose classic function is to
      regulate the permeability of tight junctions in epithelia. They are tetraspanins,
      with four alpha-helices crossing the membrane, two extracellular loops, a short
      cytoplasmic N-terminus and a longer and more variable C-terminus. The
      extracellular ends of the helices are known to undergo side-to-side (cis)
      interactions that allow the formation of claudin polymers in the plane of the
      membrane. The extracellular loops also engage in head-to-head (trans)
      interactions thought to mediate the formation of tight junctions. However,
      claudins are also present in intracellular structures, thought to be vesicles,
      with less well-characterized functions. Here, we briefly review our current
      understanding of claudin structure and function followed by an examination of
      changes in claudin mRNA and protein expression and localization through mammary
      gland development. Claudins-1, 3, 4, 7, and 8 are the five most prominent members
      of the claudin family in the mouse mammary gland, with varied abundance and
      intracellular localization during the different stages of post-pubertal
      development. Claudin-1 is clearly localized to tight junctions in mammary ducts
      in non-pregnant non-lactating animals. Cytoplasmic puncta that stain for claudin
      7 are present throughout development. During pregnancy claudin-3 is localized
      both to the tight junction and basolaterally while claudin-4 is found only in
      sparse puncta. In the lactating mouse both claudin-3 and claudin-8 are localized
      at the tight junction where they may be important in forming the paracellular
      barrier. At involution and under challenge by lipopolysaccharide claudins -1, -3,
      and -4 are significantly upregulated. Claudin-3 is still colocalized with tight
      junction molecules but is also distributed through the cytoplasm as is claudin-4.
      These largely descriptive data provide the essential framework for future
      mechanistic studies of the function and regulation of mammary epithelial cell
      claudins.

PMID- 28455728
TI  - Editorial: Getting the Most from What You Read in Orthopaedic Journals.

PMID- 28455729
TI  - CORR Insights(r): Can a Three-component Prosthesis be Used for Conversion of
      Painful Ankle Arthrodesis to Total Ankle Replacement?

PMID- 28455730
TI  - Knee Abduction Affects Greater Magnitude of Change in ACL and MCL Strains Than
      Matched Internal Tibial Rotation In Vitro.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injures incur over USD 2 billion in
      annual medical costs and prevention has become a topic of interest in
      biomechanics. However, literature conflicts persist over how knee rotations
      contribute to ACL strain and ligament injury. To maximize the efficacy of ACL
      injury prevention, the effects of underlying mechanics need to be better
      understood. QUESTIONS/PURPOSES: We applied robotically controlled, in vivo
      derived kinematic stimuli to the knee to assess ligament biomechanics in a
      cadaver model. We asked: (1) Does the application of abduction rotation increase
      ACL and medial collateral ligament (MCL) strain relative to the normal condition?
      (2) Does the application of internal tibial rotation impact ACL strain relative
      to the neutral condition? (3) Does combined abduction and internal tibial
      rotation increase ligament strain more than either individual contribution?
      METHODS: A six-degree-of-freedom robotic manipulator was used to position 17
      cadaveric specimens free from knee pathology outside of low-grade osteoarthritis
      (age, 47 +/- 8 years; 13 males, four females) into orientations that mimic
      initial contact recorded from in vivo male and female drop vertical jump and
      sidestep cutting activities. Four-degree rotational perturbations were applied in
      both directions from the neutral alignment position (creating an 8 degrees 
      range) for each frontal, transverse, and combined planes while ACL and MCL
      strains were continuously recorded with DVRT strain gauges implanted directly on
      each ligament. Analysis of variance models with least significant difference post
      hoc analysis were used to assess differences in ligament strain and joint loading
      between sex, ligament condition, or motion task and rotation type. RESULTS: For
      the female drop vertical jump simulation in the intact knee, isolated abduction
      and combined abduction/internal rotational stimuli produced the greatest change
      in strain from the neutral position as compared with all other stimuli within the
      ACL (1.5% +/- 1.0%, p <= 0.035; 1.8% +/- 1.3%, p <= 0.005) and MCL (1.8% +/-
      1.0%, p < 0.001; 1.6% +/- 1.3%, p < 0.001) compared with all other applied
      stimuli. There were no differences in mean peak ACL strain between any rotational
      stimuli (largest mean difference = 2.0%; 95% confidence interval [CI], -0.9% to
      5.0%; p = 0.070). These trends were consistent for all four simulated tasks. Peak
      ACL strain in the intact knee was larger than peak MCL strain for all applied
      rotational stimuli in the drop vertical jump simulations (smallest mean
      difference = 2.1%; 95% CI, -0.4% to 4.5%; p = 0.047). CONCLUSIONS: Kinematically
      constrained cadaveric knee models using peak strain as an outcome variable
      require greater than 4 degrees  rotational perturbations to elicit changes in
      intraarticular ligaments. CLINICAL RELEVANCE: Because combined rotations and
      isolated abduction produced greater change in strain relative to the neutral
      position for the ACL and MCL than any other rotational stimuli in this cadaver
      study, hypotheses for in vivo investigations aimed toward injury prevention that
      focuses on the reduction of frontal plane knee motion should be considered.
      Furthermore, reduced strain in the MCL versus the ACL may help explain why only
      30% of ACL ruptures exhibit concomitant MCL injuries.

PMID- 28455731
TI  - Trends in land use and land cover change in the protected and communal areas of
      the Zambezi Region, Namibia.
AB  - Land management decisions have extensively modified land use and land cover in
      the Zambezi Region. These decisions are influenced by land tenure
      classifications, legislation, and livelihoods. Land use and land cover change is
      an important indicator for quantifying the effectiveness of different land
      management strategies. However, there has been no evidence on whether protected
      or communal land tenure is more affected by land use and land cover changes in
      southern Africa and particularly Namibia. Our study attempted to fill this gap by
      analyzing the relationship between land use and land cover change and land tenure
      regimes stratified according to protected and communal area in the Zambezi
      Region. Multi-temporal Landsat TM and ETM+ imagery were used to determine the
      temporal dynamics of land use and land cover change from 1984 to 2010. The
      landscape showed distinctive modifications over the study period; broad trends
      include the increase in forest land after 1991. However, changes were not uniform
      across the study areas. Two landscape development stages were deduced: (1) 1984
      1991 represented high deforestation and gradual increase in shrub land; (2) 1991
      2000 and 2000-2010 represented lower deforestation and slower agropastoral
      expansion. The results further show clear patterns of the dynamics, magnitude,
      and direction of land use and land cover change by tenure regime. The study
      concluded that land tenure has a direct impact on land use and land cover, since
      it may restrict some activities carried out on the land in the Zambezi Region.

PMID- 28455732
TI  - Using public participation to sample trace metals in lake surface sediments: the
      OPAL Metals Survey.
AB  - Members of the public in England were invited in 2010 to take part in a national
      metals survey, by collecting samples of littoral sediment from a standing water
      body for geochemical analysis. To our knowledge, this is the first national
      sediment metals survey using public participation and reveals a snapshot of the
      extent of metals contamination in ponds and lakes across England. Hg, Ni, Cu, Zn
      and Pb concentrations exceeding sediment quality guidelines for the health of
      aquatic biota are ubiquitous in ponds and lakes, not just in areas with a legacy
      of industrial activity. To validate the public sampling approach, a calibration
      exercise was conducted at ten water bodies selected to represent a range of lakes
      found across England. Sediment concentrations of Hg, Ni, Cu, Zn and Pb were
      measured in samples of soil, stream and littoral and deep water sediment to
      assess inputs. Significant differences between littoral sediment metal
      concentrations occur due to local variability, but also organic content,
      especially in upland, peat soil catchments. Variability of metal concentrations
      between littoral samples is shown to be low in small (<20 ha) lowland lakes.
      Larger and upland lakes with more complex inputs and variation in organic content
      of littoral samples have a greater variability. Collection of littoral sediments
      in small lakes and ponds, with or without voluntary participation, can provide a
      reliable sampling technique for the preliminary assessment of metal contamination
      in standing waters. However, the heterogeneity of geology, soils and
      history/extent of metal contamination in the English landscape, combined with the
      random nature of sample collection, shows that systematic sampling for evaluating
      the full extent of metal contamination in lakes is still required.

PMID- 28455733
TI  - Carotid atherosclerotic plaques standardised uptake values: software challenges
      and reproducibility.
AB  - BACKGROUND: Positron emission tomography-computed tomography (PET-CT) carotid
      standardised uptake values (SUV) of 18F-fluorodeoxyglucose (18FDG) have been
      proposed as an inflammatory biomarker for determining cerebrovascular diseases
      such as stroke. Consideration of varying methodological approaches and software
      packages is critical to the calculation of accurate SUVs in cross-sectional and
      longitudinal patient studies. The aim of this study was to investigate whether or
      not carotid atherosclerotic plaque SUVs are consistent and reproducible between
      software packages. 18FDG-PET SUVs of carotids were taken in 101 patients using
      two different software packages. Quality assurance checks were performed to
      standardise techniques before commencing the analysis where data from five to
      seven anatomical sites were measured. A total of ten regions of interest were
      drawn on each site analysed. Statistical analyses were then performed to compare
      SUV measurements from the two software packages and to explore reproducibility of
      measurements. Lastly, the time taken to complete each analysis was measured and
      compared. RESULTS: Statistically significant differences in SUV measurements,
      between the two software packages, ranging from 9 to 21.8% were found depending
      on ROI location. In 79% (n = 23) of the ROI locations, the differences between
      the SUV measurements from each software package were found to be statistically
      significant. The time taken to perform the analyses and export data from the
      software packages also varied considerably. CONCLUSIONS: This study highlights
      the importance of standardising all aspects of methodological approaches to
      ensure accuracy and reproducibility. Physicians must be aware that when a PET-CT
      data set is analysed, subsequent follow-ups must be verified, if possible, with
      the same software package or cross-calibration between packages should be
      performed.

PMID- 28455734
TI  - Formula for predicting OSA and the Apnea-Hypopnea Index in Koreans with suspected
      OSA using clinical, anthropometric, and cephalometric variables.
AB  - PURPOSE: This study developed formulas to predict obstructive sleep apnea (OSA)
      and the Apnea-Hypopnea Index (AHI) in Korean patients with suspected OSA using
      clinical, anthropometric, and cephalometric variables. METHODS: We evaluated
      relevant variables in 285 subjects with suspected OSA. These included demographic
      characteristics, sleep-related symptoms, medical history, clinical scales,
      anthropometric measurements including facial surface measurements, and
      cephalometric measurements. All participants underwent full-night laboratory
      polysomnography. The prediction formula for the probability of OSA was created by
      logistic regression analysis and confirmed by the bootstrap resampling technique.
      The formula for predicting the AHI was developed using multiple linear regression
      analysis. RESULTS: The probability of having OSA was as follows: p = 1 / (1 +
      exponential (exp)-f ), where f = -16.508 + 1.445 * loudness of snoring 4 + 0.485
      * loudness of snoring 3 + 0.078 * waist circumference + 0.209 * subnasale-to
      stomion distance + 0.183 * thickness of the uvula (UTH) supine + 0.041 * age. The
      AHI prediction formula was as follows: -112.606 + 3.516 * body mass index + 0.683
      * mandibular plane-hyoid supine + 10.915 * loudness of snoring 4 + 6.933 *
      loudness of snoring 3 + 1.297 * UTH supine + 0.272 * age. CONCLUSION: This is the
      first study to establish formulas to predict OSA and the AHI in Koreans with
      suspected OSA using cephalometric and other variables. These results will
      contribute to prioritizing the order in which patients with suspected OSA are
      referred for polysomnography.

PMID- 28455735
TI  - Public priorities for osteoporosis and fracture research: results from a general
      population survey.
AB  - : This is the first national study of public and patient research priorities in
      osteoporosis and fracture. We have identified new research areas of importance to
      members of the public, particularly 'access to information from health
      professionals'. The findings are being incorporated into the research strategy of
      the National Osteoporosis Society. PURPOSE: This study aimed to prioritise, with
      patients and public members, research topics for the osteoporosis research
      agenda. METHODS: An e-survey to identify topics for research was co-designed with
      patient representatives. A link to the e-survey was disseminated to supporters of
      the UK National Osteoporosis Society (NOS) in a monthly e-newsletter. Responders
      were asked to indicate their top priority for research across four topics
      (understanding and preventing osteoporosis, living with osteoporosis, treating
      osteoporosis and treating fractures) and their top three items within each topic.
      Descriptive statistics were used to describe demographics and item ranking. A
      latent class analysis was applied to identify a substantive number of clusters
      with different combinations of binary responses. RESULTS: One thousand one
      hundred eighty-eight (7.4%) respondents completed the e-survey. The top three
      items overall were 'Having easy access to advice and information from health
      professionals' (63.8%), 'Understanding further the safety and benefit of
      osteoporosis drug treatments' (49.9%) and 'Identifying the condition early by
      screening' (49.2%). Latent class analysis revealed distinct clusters of responses
      within each topic including primary care management and self-management. Those
      without a history of prior fracture or aged under 70 were more likely to rate
      items within the cluster of self-management as important (21.0 vs 12.9 and 19.8
      vs 13.3%, respectively). CONCLUSION: This is the first study of public research
      priorities in osteoporosis and has identified new research areas of importance to
      members of the public including access to information. The findings are being
      incorporated into the research strategy of the National Osteoporosis Society.

PMID- 28455736
TI  - Concomitant glenohumeral pathologies associated with acute and chronic grade III
      and grade V acromioclavicular joint injuries.
AB  - PURPOSE: The purpose of this study was to identify the risk of concomitant
      glenohumeral pathologies with acromioclavicular joint injuries grade III and V.
      METHODS: Patients who underwent arthroscopically-assisted stabilization of
      acromioclavicular joint injuries grade III or grade V between 01/2007 and 12/2015
      were identified in the patient databases of two surgical centres. Gender, age at
      index surgery, grade of acromioclavicular joint injury (Rockwood III or Rockwood
      V), and duration between injury and index surgery (classified as acute or
      chronic) were of interest. Concomitant glenohumeral pathologies were noted and
      their treatment was classified as debridement or reconstructive procedure.
      RESULTS: A total of 376 patients (336 male, 40 female) were included. Mean age at
      time of arthroscopic acromioclavicular joint reconstruction surgery was 42.1 +/-
      14.0 years. Overall, 201 patients (53%) had one or more concomitant glenohumeral
      pathologies. Lesions of the biceps tendon complex and rotator cuff were the most
      common. Forty-five patients (12.0%) had concomitant glenohumeral pathologies that
      required an additional repair. The remaining 156 patients (41.5%) received a
      debridement of their concomitant pathologies. Rockwood grade V compared to
      Rockwood grade III (p = 0.013; odds ratio 1.7), and chronic compared to acute
      injury were significantly associated with having a concomitant glenohumeral
      pathology (p = 0.019; odds ratio 1.7). The probability of having a concomitant
      glenohumeral pathology was also significantly associated with increasing age (p <
      0.0001). CONCLUSIONS: Concomitant glenohumeral pathologies were observed in 53%
      of surgically treated patients with an acute or chronic acromioclavicular joint
      injury of either grade III or V. Twenty-two percent of these patients with
      concomitant glenohumeral pathologies received an additional dedicated repair
      procedure. Although a significant difference in occurrence of concomitant
      glenohumeral pathologies was seen between Rockwood grades III and V, and between
      acute and chronic lesions, increasing age was identified as the most dominant
      predictor. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 28455737
TI  - Treatment of irreparable cuff tears with smoothing of the humeroscapular motion
      interface without acromioplasty.
AB  - PURPOSE: We sought to determine whether shoulders with irreparable rotator cuff
      tears and retained active elevation can be durably improved using a conservative
      surgical procedure that smoothes the interface between the proximal humeral
      convexity and the concave undersurface of the coracoacromial arch followed by
      immediate range of motion exercises. METHODS: We reviewed 151 patients with a
      mean age of 63.4 (range 40-90) years at a mean of 7.3 (range 2-19) years after
      this surgery. RESULTS: In 77 shoulders with previously unrepaired irreparable
      tears, simple shoulder test (SST) scores improved from an average of 4.6 (range 0
      12) to 8.5 (range 1-12) (p < 0.001). Fifty-four patients (70%) improved by at
      least the minimally clinically important difference (MCID) of 2 SST points. For
      74 shoulders with irreparable failed prior repairs, SST scores improved from 4.0
      (range 0-11) to 7.5 (range 0-12) (p < 0.001). Fifty-four patients (73%) improved
      by the MCID of 2 SST points. CONCLUSION: Smoothing of the humeroscapular
      interface can improve symptomatic shoulders with irreparable cuff tears and
      retained active elevation. This conservative procedure offers an alternative to
      more complex procedures in the management of irreparable rotator cuff tears.
      LEVEL OF EVIDENCE: Level IV.

PMID- 28455738
TI  - Mental imagery skills predict the ability in performing environmental directional
      judgements.
AB  - Mental imagery plays a crucial role in several cognitive processes, including
      human navigation. According to the Kosslyn's Model, mental imagery is subserved
      by three components: generation, inspection and transformation. The role of
      transformation, where by individuals recognise, from a different perspective, a
      place they have already visited, is no longer a matter of debate. However, the
      role of the other two components when recalling a map from different
      perspectives, has never been fully investigated. In the present study, we
      enrolled forty-nine college students and asked them to learn a schematic map and
      to provide directional judgements aligned or counter-aligned compared to the
      learnt map orientation. Their mental imagery generation, inspection and
      transformation skills were also investigated. Results demonstrated that all three
      visual mental imagery components negatively correlate with errors in providing
      directional judgements. Specifically, generation assumes a role in aligned
      directional judgements, while inspection and transformation predict the
      capability to provide counter-aligned directional judgements. Although all mental
      imagery components play a role in mentally recalling a map, only the proficiency
      in inspection and mental rotation can predict the accuracy in changing
      perspective.

PMID- 28455739
TI  - Postural responses in the upper limbs evoked by axial impulses: a role for
      reticulospinal projections.
AB  - We studied the short-latency (SL) postural effects of axial impulses in 11
      subjects (22 +/- 2 years old). Recordings were made bilaterally from soleus and
      tibialis anterior (TA) muscles. We confirmed that with leaning anteriorly and
      posteriorly, reflex EMG increases occurred in both muscle groups at short latency
      following brief perturbations applied over C7 or the sternum (soleus mean
      latencies 57.5 and 66.4 ms; TA mean 51.7 and 55.4 ms, respectively). While the
      size of the SL reflexes was affected by the direction of lean when standing we
      found that light touch did not affect the amplitudes or latencies significantly.
      We investigated the presence of SL responses in the upper limb muscle triceps
      brachii during an isometric contraction and when the arm muscles had a direct
      role in supporting approximately 40% of the body weight. Similar levels of tonic
      EMG activity occurred in triceps in both conditions but significantly larger SL
      reflexes occurred when used posturally compared to the isometric contraction
      (23.0 vs 3.3%) while the reverse occurred for SL responses in soleus and TA,
      which were significantly attenuated. The responses were present with the head in
      the neutral position but with head rotation were larger contralateral to the
      direction of rotation. Calculations based upon the relative latencies suggest
      that the pathway responsible is not the corticospinal tract. We conclude that
      axially evoked SL postural reflexes are unaffected by light tactile input but are
      present in upper limb muscles when used for postural support. We propose that the
      pathway mediating these responses is the reticulospinal tract.

PMID- 28455740
TI  - Motor equivalence and structure of variance: multi-muscle postural synergies in
      Parkinson's disease.
AB  - We explored posture-stabilizing multi-muscle synergies with two methods of
      analysis of multi-element, abundant systems: (1) Analysis of inter-cycle
      variance; and (2) Analysis of motor equivalence, both quantified within the
      framework of the uncontrolled manifold (UCM) hypothesis. Data collected in two
      earlier studies of patients with Parkinson's disease (PD) were re-analyzed. One
      study compared synergies in the space of muscle modes (muscle groups with
      parallel scaling of activation) during tasks performed by early-stage PD patients
      and controls. The other study explored the effects of dopaminergic medication on
      multi-muscle-mode synergies. Inter-cycle variance and absolute magnitude of the
      center of pressure displacement across consecutive cycles were quantified during
      voluntary whole-body sway within the UCM and orthogonal to the UCM space. The
      patients showed smaller indices of variance within the UCM and motor equivalence
      compared to controls. The indices were also smaller in the off-drug compared to
      on-drug condition. There were strong across-subject correlations between the
      inter-cycle variance within/orthogonal to the UCM and motor equivalent/non-motor
      equivalent displacements. This study has shown that, at least for cyclical tasks,
      analysis of variance and analysis of motor equivalence lead to metrics of
      stability that correlate with each other and show similar effects of disease and
      medication. These results show, for the first time, intimate links between
      indices of variance and motor equivalence. They suggest that analysis of motor
      equivalence, which requires only a handful of trials, could be used broadly in
      the field of motor disorders to analyze problems with action stability.

PMID- 28455741
TI  - Lymphoepithelioma-like carcinoma of the upper urinary tract.
AB  - In this report, we summarized the clinicopathologic features of ten cases of
      lymphoepithelioma-like carcinoma (LELC) of the upper urinary tract (ureter n = 6;
      renal pelvis n = 4), a rare variant of urothelial cancer characterized by a
      malignant epithelial component densely infiltrated by lymphoid cells. The initial
      diagnosis was made on radical nephrectomy in five cases, nephroureterectomy in
      three cases, and ureterectomy in two others. Four patients had pathologic stage
      T1 (n = 2) or T2 (n = 2) tumors, and six patients had stage pT3 disease.
      Microscopically, all tumors contained pure (n = 3) or predominant (n = 7) LELC,
      which composed 60 to 80% of the entire tumor. Non-LELC tumor component was
      adenocarcinoma (n = 2), spindle cell carcinoma (n = 1), or high-grade
      conventional urothelial carcinoma (n = 4). The LELC component was characterized
      by indistinct cytoplasmic borders and a syncytial growth pattern.
      Immunohistochemical staining showed LELC to be positive for cytokeratin AE1/AE3,
      CK7, CK34betaE12 (rare cells), CK5/6 (rare cells), and CK20 (rare cells); rare
      cells were p40 positive. GATA 3 was positive in all cases in a variable
      proportion of cells (20-80%). Lymphoid markers showed a polyclonal proliferation
      of predominant T cells admixed with B cells. In situ hybridization for the HPV
      genome was negative in all ten cases. Survival analysis showed no differences
      between LELC and conventional upper urinary tract urothelial carcinoma, pT
      classification being the only significant prognostic parameter. Morphologic
      recognition and distinction from other (non-)neoplastic lesions with prominent
      lymphoid stroma are critical for its clinical management.

PMID- 28455743
TI  - Topical issue on non-isothermal transport in complex fluids.

PMID- 28455742
TI  - Eosinophilic Otitis Media: the Aftermath of Eosinophil Extracellular Trap Cell
      Death.
AB  - PURPOSE OF REVIEW: Eosinophilic otitis media (EOM) is a refractory disease
      characterized by the accumulation of eosinophils in middle ear effusion and
      mucosa. We summarize current knowledge regarding the clinical characteristics and
      management of EOM. Although eosinophil activation in inflamed foci is involved in
      the pathogenesis of EOM, little is known about the fate of the eosinophils and
      aftermath of their cell death. We discuss the possibility that eosinophils
      undergo non-apoptotic cell death that worsens tissue damage and increases
      effusion viscosity. RECENT FINDINGS: Unlike chronic otitis media, EOM is strongly
      associated with an allergic background. Corticosteroids are currently the only
      effective pharmacological treatment, and surgical intervention is often required.
      Mucosal eosinophils infiltrate extensively into the middle ear cavity where they
      are stimulated by locally produced activators including interleukin-5 and
      eotaxin. The eosinophils undergo cytolysis in the effusion, which represents a
      major fate of activated eosinophils in vivo. Recent data revealed cytolysis could
      be renamed as extracellular trap cell death (ETosis). ETosis represents suicidal
      cell death involving total cell degranulation and development of sticky chromatin
      structures (extracellular traps (ETs)). The characteristics of eosinophil- and
      neutrophil-derived ET polymers might contribute to the difference in viscosity of
      secretions between EOM and common chronic otitis media. The extracellular
      products remaining after eosinophil ETosis are an important aspect of EOM
      pathology. The concept of ETosis also has novel implications for potential
      therapeutic modalities in various eosinophilic disorders.

PMID- 28455744
TI  - Stability of a gravity-driven thin electrolyte film flowing over a heated
      substrate.
AB  - The stability of a thin electrolyte liquid film driven by gravity over a vertical
      substrate is presented. A film thickness evolution equation is derived and solved
      numerically. The substrate is non-uniformly heated from below which is modeled by
      imposing a temperature profile at the liquid-solid interface. The
      electrohydrodynamics is included in the model with Maxwell's stress tensor. The
      governing flow and energy equations are simplified using the lubrication
      approximation. The Poisson-Boltzmann equation with Debye-Huckel approximation is
      used for the potential which is generated inside the film due to a charged layer
      at the liquid-solid interface. The positive temperature gradient at the substrate
      leads to the formation of a thermocapillary ridge due to an opposing Marangoni
      stress. This thermocapillary ridge becomes unstable beyond critical parameters
      related to Marangoni stress and convective energy loss at the free surface. The
      electroosmotic flow has no effect on the base profile of the film, but enhances
      its instability. A parameter space is presented delineating the stable and
      unstable regimes for the film dynamics.

PMID- 28455746
TI  - Cephalometric changes in growing patients with increased vertical dimension
      treated with cervical headgear.
AB  - PURPOSE: The aim of the present study was to investigate the cephalometric
      changes in patients with increased vertical dimension after treatment with
      cervical headgear compared to controls. METHODS: The sample of the present
      retrospective study consisted of 20 Class II patients (10 males, 10 females; mean
      age 8.54 +/- 1.15 years) with increased vertical dimension treated with cervical
      headgear (treatment group) and 21 Class II patients (11 males, 10 females; mean
      age 8.41 +/- 1.15 years) with increased vertical dimension who underwent no
      treatment (control group). Cephalograms were available for each subject at
      baseline (T1) and after treatment/observation time (T2) for both groups and
      cephalometric analysis allowed for evaluation of changes between time points and
      between groups. RESULTS: Regarding facial axis, N-ANS/ANS-Me, and overbite, there
      were no negatively significant changes in the treated group showing no
      significant worsening in the vertical dimension. Regarding facial angle, there
      was a significant increase in the treated group between the time points and when
      compared to the control group, showing counterclockwise rotation of the mandible
      in the treated group. CONCLUSIONS: The vertical dimension was not significantly
      altered after cervical headgear treatment although the anterior facial height was
      higher at the beginning of treatment. There was significant counterclockwise
      rotation of the mandible, and clockwise rotation and distal displacement of the
      maxilla after treatment.

PMID- 28455745
TI  - Expanding the role of vasopressin antagonism in polycystic kidney diseases: From
      adults to children?
AB  - Polycystic kidney disease (PKD) encompasses a group of genetic disorders that are
      common causes of renal failure. The two classic forms of PKD are autosomal
      recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic
      kidney disease (ADPKD). Despite their clinical differences, ARPKD and ADPKD share
      many similarities. Altered intracellular Ca2+ and increased cyclic adenosine
      monophosphate (cAMP) concentrations have repetitively been described as central
      anomalies that may alter signaling pathways leading to cyst formation. The
      vasopressin V2 receptor (V2R) antagonist tolvaptan lowers cAMP in cystic tissues
      and slows renal cystic progression and kidney function decline when given over 3
      years in adult ADPKD patients. Tolvaptan is currently approved for the treatment
      of rapidly progressive disease in adult ADPKD patients. On the occasion of the
      recent initiation of a clinical trial with tolvaptan in pediatric ADPKD patients,
      we aim to describe the most important aspects in the literature regarding the AVP
      cAMP axis and the clinical use of tolvaptan in PKD.

PMID- 28455747
TI  - Oxidative stress promotes myocardial fibrosis by upregulating KCa3.1 channel
      expression in AGT-REN double transgenic hypertensive mice.
AB  - The intermediate-conductance Ca2+-activated K+ (KCa3.1) channels play a pivotal
      role in the cardiac fibroblast proliferation and inflammatory reaction during the
      progression of myocardial fibrosis. However, the relationship between KCa3.1
      expression and oxidative stress, the important factor of promoting fibrosis, has
      not been clearly established. This study was designed to investigate whether the
      role of oxidative stress in promoting myocardial fibrosis is related to KCa3.1
      channel by using biochemical approaches. It was found that mean blood pressure,
      plasma Ang II level, and myocardium malondialdehyde (MDA) content of
      angiotensinogen-renin (AGT-REN) double transgenic hypertension (dTH) mice were
      higher than those in wild-type (WT) mice of the same age (4, 8 and 12 months) and
      were significantly increased with age. However, plasma Ang (1-7) level and
      myocardium superoxide dismutase (SOD) activity showed a downward trend and were
      lower than those of the same-aged WT mice (4, 8 and 12 months). In addition,
      protein expression of myocardium KCa3.1 channel in 4-, 8-, and 12-month-old dTH
      mice were significantly higher than that of the same-aged WT mice and gradually
      increased with age. TRAM-34, a blocker of KCa3.1 channel, and losartan mitigated
      the myocardial structural and functional damage by inhibiting collagen deposition
      and decreasing the expression of beta-MHC. After intervention of ROS scavenger N
      acetyl cysteine (NAC) and NADPH inhibitor apocynin (Apo) in 6-month-old dTH mice
      for 4 weeks, myocardial oxidative stress level was reduced and KCa3.1 channel
      protein expression was decreased. Meanwhile, Apo inhibited the myocardium p
      ERK1/2/T-ERK protein expression in dTH mice, and after blockage of ERK1/2 pathway
      with PD98059, the KCa3.1 protein expression was reduced. These results
      demonstrate for the first time that KCa3.1 channel is likely to be a critical
      target on the oxidative stress for its promoting role in myocardial fibrosis, and
      the ERK1/2 pathway may be involved in the regulation of oxidative stress to
      KCa3.1.

PMID- 28455748
TI  - CK2 is a key regulator of SLC4A2-mediated Cl-/HCO3- exchange in human airway
      epithelia.
AB  - Transepithelial bicarbonate secretion by human airway submucosal glands and
      surface epithelial cells is crucial to maintain the pH-sensitive innate defence
      mechanisms of the lung. cAMP agonists stimulate HCO3- secretion via coordinated
      increases in basolateral HCO3- influx and accumulation, as well as CFTR-dependent
      HCO3- efflux at the luminal membrane of airway epithelial cells. Here, we
      investigated the regulation of a basolateral located, DIDS-sensitive, Cl-/HCO3-
      exchanger, anion exchanger 2 (AE2; SLC4A2) which is postulated to act as an acid
      loader, and therefore potential regulator of HCO3- secretion, in human airway
      epithelial cells. Using intracellular pH measurements performed on Calu-3 cells,
      we demonstrate that the activity of the basolateral Cl-/HCO3- exchanger was
      significantly downregulated by cAMP agonists, via a PKA-independent mechanism and
      also required Ca2+ and calmodulin under resting conditions. AE2 contains
      potential phosphorylation sites by a calmodulin substrate, protein kinase CK2,
      and we demonstrated that AE2 activity was reduced in the presence of CK2
      inhibition. Moreover, CK2 inhibition abolished the activity of AE2 in primary
      human nasal epithelia. Studies performed on mouse AE2 transfected into HEK-293T
      cells confirmed almost identical Ca2+/calmodulin and CK2 regulation to that
      observed in Calu-3 and primary human nasal cells. Furthermore, mouse AE2 activity
      was reduced by genetic knockout of CK2, an effect which was rescued by exogenous
      CK2 expression. Together, these findings are the first to demonstrate that CK2 is
      a key regulator of Cl--dependent HCO3- export at the serosal membrane of human
      airway epithelial cells.

PMID- 28455749
TI  - Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals
      in a Danish population.
AB  - : Bone turnover markers are used for monitoring osteoporosis treatment.
      Therefore, we evaluated the agreement between different assays for CTX and PINP
      and established reference intervals in a cohort of 2300 individuals. We found
      poor agreement between assays and different reference intervals. This highlights
      the importance of harmonization of the assays. INTRODUCTION: Two reference
      markers for bone turnover have been proposed: CTX bone resorption and P1NP for
      bone formation. The purpose of the current study was to establish reference
      intervals for the two markers in a Danish cohort and to determine the agreement
      on the two platforms. METHODS: Fasting sera from 2308 individuals (1250 males and
      1058 females, age range 24-76 years) participating in the Health2006 study were
      analyzed for CTX and P1NP using the automated IDS-iSYS analyzer and the automated
      Cobas e411 analyzer. Participants in anti-osteoporotic treatment were excluded,
      while subjects on hormonal contraceptives were included. RESULTS: There was
      significant disagreement between both the two P1NP assays with a mean difference
      of -3 MUg/L (LoA -19 to 14) (p < 0.001) and the two CTX assays with a mean
      difference of 13 ng/L (LoA-187 to 214) (p < 0.001). For CTX, there was a
      systematic bias: at low values, Cobas measured a higher value than iSYS and at
      higher concentrations, iSYS measured increasingly higher values than Cobas. Based
      on the results, we propose three reference intervals for each sex: 25-29, 30-39,
      and 40-80 years for men, and 25-29, >30 (pre-menopausal), and >30 years (post
      menopausal) for women. CONCLUSIONS: There is significant disagreement between the
      IDS-iSYS and Roche Cobas assays for both reference markers. Consequently, the
      reference intervals for an adult, healthy population are different depending on
      the analysis method used. Therefore, repeated measurements of patient samples
      used for monitoring of treatment should be done on the same assay. Moreover,
      assay-specific reference intervals should be used. Harmonization of assays for
      BTM is highly warranted.

PMID- 28455750
TI  - Use of dipeptidyl peptidase-4 inhibitors and risk of bone fracture in patients
      with type 2 diabetes in Germany-A retrospective analysis of real-world data.
AB  - : In type 2 diabetes patients treated in German primary care practices, the use
      of dipeptidyl peptidase-4 inhibitor (DPP4i) in combination with metformin was
      associated with a significant decrease in the risk of developing bone fractures
      compared to metformin monotherapy. INTRODUCTION: The goal of this study was to
      analyze the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) use on the risk of
      bone fracture in patients diagnosed with type 2 diabetes mellitus (T2DM) in
      Germany. METHODS: Patients with an initial prescription of metformin between 2008
      and 2014 from 1262 German general practitioner practices were selected. We
      matched 4160 DPP4i ever users to never users (1:1) based on age, sex, diabetes
      duration, body mass index, index year, and physician type. The primary outcome
      measure was the rate of bone fractures within five years of the start of
      metformin or DPP-4i therapy. Time-dependent Cox regression models were used to
      estimate hazard ratios (HRs) for fractures as a function of the DPP4i therapy.
      RESULTS: The mean age among the patients was 61.6 years (SD = 11.1 years), 59.6%
      were men, and 3.1% were followed in diabetologist practices. The mean diabetes
      duration was 1.5 years (SD = 2.4 years), HbA1c levels were 7.1% in DPP4i users
      and 6.6% in non-users, and body mass index was 31.5 kg/m2 (SD = 5.0 kg/m2).
      Within five years of the index date, 6.4% of users and 8.3% of non-users
      developed bone fractures (log-rank p-value < 0.001). Within five years of the
      index date, 7.4% of female and 4.7% of male users and 13.3% of female and 8.8% of
      male non-users were diagnosed with bone fractures (both log-rank p-values <
      0.001). The use of DPP4i was associated with a significant decrease in the risk
      of developing bone fractures (all patients HR = 0.67, 95% CI 0.54-0.84; women HR
      = 0.72, 95% CI 0.54-0.97; men HR = 0.62, 95% CI 0.44-0.88). CONCLUSION: DPP4i use
      was associated with a decrease in the risk of bone fracture.

PMID- 28455751
TI  - National trends and outcomes of autologous in vitro fertilization cycles among
      women ages 40 years and older.
AB  - PURPOSE: The purpose of the study was to describe trends in and investigate
      variables associated with clinical pregnancy and live birth in autologous in
      vitro fertilization (IVF) cycles among women >=40 years. METHODS: We used
      autologous IVF cycle data from the National ART Surveillance System (NASS) for
      women >=40 years at cycle start. We assessed trends in fresh and frozen cycles (n
      = 371,536) from 1996 to 2013. We reported perinatal outcomes and determined
      variables associated with clinical pregnancy and live birth in fresh cycles
      between 2007 and 2013. RESULTS: From 1996 to 2013, the total number of cycles in
      women >=40 years increased from 8672 to 28,883 (p < 0.0001), with frozen cycles
      almost tripling in the last 8 years. Cycles in women >=40 years accounted for
      16.0% of all cycles in 1996 and 21.0% in 2013 (p < 0.0001). For fresh cycles from
      2007 to 2013 (n = 157,890), the cancelation rate was 17.1%. Among cycles
      resulting in transfer (n = 112,414), the live birth rate was 16.1%. The following
      were associated with higher live birth rates: multiparity, fewer prior ART
      cycles, use of standard agonist or antagonist stimulation, lower gonadotropin
      dose, ovarian hyperstimulation syndrome, more oocytes retrieved, use of pre
      implantation genetic screening/diagnosis, transferring more and/or blastocyst
      stage embryos, and cryopreserving more supernumerary embryos. Of the singleton
      infants born (n = 14,992), 86.9% were full term and 88.3% normal birth weight.
      CONCLUSIONS: The NASS allows for a comprehensive description of IVF cycles in
      women >=40 years in the USA. Although live birth rate is less than 20%,
      identifying factors associated with IVF success can facilitate treatment option
      counseling.

PMID- 28455752
TI  - Erratum to: The association between coenzyme Q10 concentrations in follicular
      fluid with embryo morphokinetics and pregnancy rate in assisted reproductive
      techniques.

PMID- 28455753
TI  - Erratum to: Dehydroepiandrosterone (DHEA) supplementation results in
      supraphysiologic DHEA-S serum levels and progesterone assay interference that may
      impact clinical management in IVF.

PMID- 28455754
TI  - DHEA supplementation can result in assay changes which may impact clinical
      decisions in IVF.

PMID- 28455760
TI  - Adapting Meaning-Centered Psychotherapy in Advanced Cancer for the Chinese
      Immigrant Population.
AB  - The Chinese immigrant community faces multiple barriers to quality cancer care
      and cancer survivorship. Meaning-centered psychotherapy (MCP) is an empirically
      based treatment shown to significantly reduce psychological distress while
      increasing spiritual well-being and a sense of meaning and purpose in life in
      advanced cancer patients. However, it has not yet been adapted for racial and
      ethnic minority populations for whom the concept of "meaning" may likely differ
      from that of westernized White populations. In this study, we conducted a
      community needs assessment to inform the cultural adaptation of MCP for Chinese
      patients with advanced cancer, in accordance with Bernal et al. ecological
      validity model and the cultural adaptation process model of Domenech-Rodriquez
      and Weiling. We conducted interviews until saturation with 11 key Chinese-serving
      community leaders and health professionals with a range of areas of expertise
      (i.e. oncology, psychology, palliative care, cancer support services), to examine
      community needs, priorities, and preferences within the context of the MCP
      intervention. Sessions were audio recorded and transcribed. The research team
      analyzed the transcripts using Atlas.ti. Six frequently occurring themes were
      identified. Interviewees described the role of the family, traditional Chinese
      values, cancer stigma, and social norms (e.g. saving face) in adapting MCP.
      Researchers and clinicians should consider the role of the family in treatment,
      as well as specific social and cultural values and beliefs in adapting and
      delivering MCP for Chinese patients with advanced cancer.

PMID- 28455761
TI  - Women's Decision-Making Autonomy and their Attitude towards Wife-Beating:
      Findings from the 2011 Ethiopia's Demographic and Health Survey.
AB  - The study examined the extent of wife-beating acceptance and factors that
      influence women's attitude towards wife-beating in Ethiopia from a nationally
      representative sample of 11,658 participants in the 2011 Ethiopian Demographic
      and Health Survey. Multivariate logistic regressions were fitted to investigate
      the relationships between women's attitude towards wife-beating and women's
      decision-making autonomy after controlling for socio-demographic factors. The
      majority (56%) of women agreed that wife-beating is justified when wife neglects
      children, 53% when wife burns the food, 50% when wife argues with husband, 48%
      when wife goes out without telling husband, and nearly 45% when wife refuses to
      have sex with husband. Overall, 51% of women had shown highly favorable attitude
      towards wife-beating. Women's place of residence, household wealth quintiles,
      educational levels, marital status, and husband/partner's employment status have
      shown significant association with women's attitude towards wife-beating. Women's
      decision-making autonomy was also a significant predictor of women's attitude
      towards wife-beating. The odds of having highly favorable attitude towards wife
      beating deceased significantly as the level of decision-making autonomy of women
      improved. Given the widespread acceptance of wife-beating among Ethiopian women,
      social policies that empower women could serve as a positive force in changing
      attitudes towards wife-beating and violence against women.

PMID- 28455762
TI  - Expression of the stress-response regulators CtsR and HrcA in the uropathogen
      Staphylococcus saprophyticus during heat shock.
AB  - The uropathogen Staphylococcus saprophyticus is an ubiquitous bacterium but
      little is known about mechanisms that allow its persistence in diverse
      environments. Here we evaluated S. saprophyticus growth and survival during heat
      shock, the expression of stress response regulators ctsR and hrcA through qRT-PCR
      and heat shock protein synthesis through 35S-Met metabolic labeling. S.
      saprophyticus does not tolerate temperatures much higher than the optimal 37 
      degrees C, as its growth is greatly affected at 42  degrees C, though viability
      is maintained up to 48  degrees C. At 42  degrees C, the expression of ctsR and
      hrcA repressor genes approximately triple when compared to 37  degrees C and
      continue to increase together with temperature till 48  degrees C. Expression of
      hrcA peaks after 20 min of heat shock and decreases significantly after 30 min,
      indicating that heat stress response regulated by this gene may last 20-30 min.
      An increase in temperature is accompanied by the synthesis of at least eight
      proteins, three of which are likely the chaperones DnaK, GroEL and ClpB. In
      silico analysis indicate that the groEL gene may be regulated by HrcA, clpB by
      CtsR and dnaK by both repressors. This is the first work to discuss heat stress
      response in S. saprophyticus and a step forward in the understanding of
      mechanisms that make this a widespread and emergent pathogen.

PMID- 28455755
TI  - Is early embryo development as observed by time-lapse microscopy dependent on
      whether fresh or frozen sperm was used for ICSI? A cohort study.
AB  - PURPOSE: The aim of this study was to compare timings of key events of embryo
      development from those originating from either fresh or cryopreserved ejaculate
      sperm using time-lapse technology. METHODS: In this retrospective observational
      cohort study, time-lapse technology was used to monitor 1927 embryos from 234
      women undergoing intracytoplasmic sperm injection (ICSI) and utilizing either
      fresh (n = 172 cycles) or cryopreserved ejaculate sperm (n = 62 cycles) for
      insemination were included in the study. Key developmental events as described in
      time-lapse were compared with the use of generalized estimating equations (GEE)
      to adjust for any auto-correlation between the observations. In addition,
      multivariable logit regression models were used to account for any known baseline
      differences between the two groups. RESULTS: There were no differences in
      conventional embryo development such as number of 8-cell embryos by 72 h (p =
      0.359), the number of blastocysts by 120 h (p = 0.417), and the number of top
      quality blastocysts (p = 0.956) between the two groups compared. There were no
      statistical differences in the timings of any of the key embryo developmental
      events (PN_t1, NEBD, cytokinesis, t2, t3, t4, t5, t6, t7, t8, tM, tSB, tEB, tHB,
      s1, s2, s3, cc2, and cc3) when either fresh or cryopreserved ejaculate sperm was
      used for ICSI. This was also confirmed with conventional morphological
      assessment. CONCLUSIONS: This observational cohort study has shown that there are
      no differences in the morphokinetic parameters of early embryo development when
      either fresh or frozen ejaculate sperm are used for ICSI insemination.

PMID- 28455763
TI  - Terrimonas suqianensis sp. nov., isolated from a tetrabromobisphenol A
      contaminated soil.
AB  - Strain C3-5T, a Gram-negative, asporogenous, rod-shaped bacterium, was isolated
      from a tetrabromobisphenol A contaminated soil. Growth was observed at 10-37 
      degrees C (optimum 30  degrees C) and at pH 5.5-9.5 (optimum pH 7.0).
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain C3-5T
      is a member of the genus Terrimonas and exhibits high sequence similarities with
      Terrimonas pekingensis QHT (99.0%) and Terrimonas rhizosphaerae CR94T (97.3%),
      and exhibits low (<97%) sequence similarities with other known Terrimonas
      species. Chemotaxonomic analysis revealed that strain C3-5T possesses menaquinone
      7 (MK-7) as the major isoprenoid quinone and iso-C15:0, iso-C15:1 G, iso-C17:0 3
      OH and summed feature 3 (C16:1 omega6c and/or C16:1 omega7c) as the major (>5% of
      total) fatty acids. The polar lipids were determined to be a lipid, glycolipid,
      phospholipid, phosphoaminolipid and phosphatidylethanolamine. The DNA G+C content
      was found to be 42.6 mol%. The DNA-DNA relatedness values with the closely
      related strains T. pekingensis QHT and T. rhizosphaerae CR94T were 25.2 and
      48.5%, respectively. Based on phylogenetic analysis, phenotypic characteristics
      and chemotaxonomic data, strain C3-5T is considered to represent a novel species
      of the genus Terrimonas, for which the name Terrimonas suqianensis sp. nov. is
      proposed. The type strain is C3-5T (= CCTCC AB 2017042T = KCTC 52676T).

PMID- 28455764
TI  - Heterologous expression of three Camellia sinensis small heat shock protein genes
      confers temperature stress tolerance in yeast and Arabidopsis thaliana.
AB  - KEY MESSAGE: CsHSP17.7, CsHSP18.1, and CsHSP21.8 expressions are induced by heat
      and cold stresses, and CsHSP overexpression confers tolerance to heat and cold
      stresses in transgenic Pichia pastoris and Arabidopsis thaliana. Small heat shock
      proteins (sHSPs) are crucial for protecting plants against biotic and abiotic
      stresses, especially heat stress. However, knowledge concerning the functions of
      Camellia sinensis sHSP in heat and cold stresses remains poorly understood. In
      this study, three C. sinensis sHSP genes (i.e., CsHSP17.7, CsHSP18.1, and
      CsHSP21.8) were isolated and characterized using suppression subtractive
      hybridization (SSH) technology. The CsHSPs expression levels in C. sinensis
      leaves were significantly up-regulated by heat and cold stresses. Phylogenetic
      analyses revealed that CsHSP17.7, CsHSP18.1, and CsHSP21.8 belong to sHSP Classes
      I, II, and IV, respectively. Heterologous expression of the three CsHSP genes in
      Pichia pastoris cells enhanced heat and cold stress tolerance. When exposed to
      heat and cold treatments, transgenic Arabidopsis thaliana plants overexpressing
      CsHSP17.7, CsHSP18.1, and CsHSP21.8 had lower malondialdehyde contents, ion
      leakage, higher proline contents, and transcript levels of stress-related genes
      (e.g., AtPOD, AtAPX1, AtP5CS2, and AtProT1) compared with the control line. In
      addition, improved seed germination vigor was also observed in the CsHSP
      overexpressing seeds under heat stress. Taken together, our results suggest that
      the three identified CsHSP genes play key roles in heat and cold tolerance.

PMID- 28455765
TI  - Generic thrombus segmentation from pre- and post-operative CTA.
AB  - PURPOSE: Abdominal aortic aneurysm (AAA) is a localized, permanent and
      irreversible enlargement of the artery, with the formation of thrombus into the
      inner wall of the aneurysm. A precise patient-specific segmentation of the
      thrombus is useful for both the pre-operative planning to estimate the rupture
      risk, and for post-operative assessment to monitor the disease evolution. This
      paper presents a generic approach for 3D segmentation of thrombus from patients
      suffering from AAA using computed tomography angiography (CTA) scans. METHODS: A
      fast and versatile thrombus segmentation approach has been developed. It is
      composed of initial centerline detection and aorta lumen segmentation, an
      optimized pre-processing stage and the use of a 3D deformable model. The approach
      has been designed to be very generic and requires minimal user interaction. The
      proposed method was tested on different datasets with 145 patients overall,
      including pre- and post-operative CTAs, abdominal aorta and iliac artery
      sections, different calcification degrees, aneurysm sizes and contrast
      enhancement qualities. RESULTS: The thrombus segmentation approach showed very
      accurate results with respect to manual delineations for all datasets ([Formula:
      see text] and [Formula: see text] for abdominal aorta sections on pre-operative
      CTA, iliac artery sections on pre-operative CTAs and aorta sections on post
      operative CTA, respectively). Experiments on the different patient and image
      conditions showed that the method was highly versatile, with no significant
      differences in term of precision. Comparison with the level-set algorithm also
      demonstrated the superiority of the 3D deformable model. Average processing time
      was [Formula: see text]. CONCLUSION: We presented a near-automatic and generic
      thrombus segmentation algorithm applicable to a large variability of patient and
      imaging conditions. When integrated in an endovascular planning system, our
      segmentation algorithm shows its compatibility with clinical routine and could be
      used for pre-operative planning and post-operative assessment of endovascular
      procedures.

PMID- 28455766
TI  - Grasper having tactile sensing function using acoustic reflection for
      laparoscopic surgery.
AB  - PURPOSE: In current minimally invasive surgery techniques, the tactile
      information available to the surgeon is limited. Improving tactile sensation
      could enhance the operability of surgical instruments. Considering surgical
      applications, requirements such as having electrical safety, a simple structure,
      and sterilization capability should be considered. The current study sought to
      develop a grasper that can measure grasping force at the tip, based on a
      previously proposed tactile sensing method using acoustic reflection. This method
      can satisfy the requirements for surgical applications because it has no
      electrical element within the part that is inserted into the patient's body.
      METHODS: We integrated our acoustic tactile sensing method into a conventional
      grasping forceps instrument. We designed the instrument so that acoustic cavities
      within a grasping arm and a fork sleeve were connected by a small cavity in a
      pivoting joint. In this design, when the angle between the two grasping arms
      changes during grasping, the total length and local curvature of the acoustic
      cavity remain unchanged. Thus, the grasping force can be measured regardless of
      the orientation of the grasping arm. RESULTS: We developed a prototype sensorized
      grasper based on our proposed design. Fundamental tests revealed that sensor
      output increased with increasing contact force applied to the grasping arm, and
      the angle of the grasping arm did not significantly affect the sensor output.
      Moreover, the results of a grasping test, in which objects with different
      softness characteristics were held by the grasper, revealed that the grasping
      force could be appropriately adjusted to handle different objects on the basis of
      sensor output. CONCLUSIONS: Experimental results demonstrated that the prototype
      grasper can measure grasping force, enabling safe and stable grasping.

PMID- 28455767
TI  - Incorporating pleiotropic quantitative trait loci in dissection of complex
      traits: seed yield in rapeseed as an example.
AB  - KEY MESSAGE: A comprehensive linkage atlas for seed yield in rapeseed. Most
      agronomic traits of interest for crop improvement (including seed yield) are
      highly complex quantitative traits controlled by numerous genetic loci, which
      brings challenges for comprehensively capturing associated markers/genes. We
      propose that multiple trait interactions underlie complex traits such as seed
      yield, and that considering these component traits and their interactions can
      dissect individual quantitative trait loci (QTL) effects more effectively and
      improve yield predictions. Using a segregating rapeseed (Brassica napus)
      population, we analyzed a large set of trait data generated in 19 independent
      experiments to investigate correlations between seed yield and other complex
      traits, and further identified QTL in this population with a SNP-based genetic
      bin map. A total of 1904 consensus QTL accounting for 22 traits, including 80 QTL
      directly affecting seed yield, were anchored to the B. napus reference sequence.
      Through trait association analysis and QTL meta-analysis, we identified a total
      of 525 indivisible QTL that either directly or indirectly contributed to seed
      yield, of which 295 QTL were detected across multiple environments. A majority
      (81.5%) of the 525 QTL were pleiotropic. By considering associations between
      traits, we identified 25 yield-related QTL previously ignored due to contrasting
      genetic effects, as well as 31 QTL with minor complementary effects.
      Implementation of the 525 QTL in genomic prediction models improved seed yield
      prediction accuracy. Dissecting the genetic and phenotypic interrelationships
      underlying complex quantitative traits using this method will provide valuable
      insights for genomics-based crop improvement.

PMID- 28455768
TI  - Sleep disturbance in mild cognitive impairment: a systematic review of objective
      measures.
AB  - Sleep disturbance frequently occurs in patients with mild cognitive impairment
      (MCI) and appears to be involved in the cellular and molecular mechanisms of
      cognitive decline. The aim of this systematic review is to clarify whether
      patients with MCI demonstrate alterations in certain sleep parameters: total
      sleep time (TST), sleep efficiency (SE), sleep latency (SL), rapid eye movement
      latency (REML), percent of rapid eye movement (REM%), arousal index (AI), wake
      after sleep onset (WASO), slow-wave sleep (SWS), periodic leg movement in sleep
      (PLMS), and cyclic alternating pattern (CAP) through polysomnography (PSG) and
      actigraphy. Databases including PubMed, Web of Science, Embase, ScienceDirect,
      Cochrane, CBM, CNKI, Wanfang Data, and VIP were searched up to January 2016 to
      collect literature on the correlation between sleep disturbance and MCI as
      assessed by objective measures. Meta-analysis was conducted using the Review
      Manager 5.3 software. A total of ten case-control studies involving 225 MCI
      patients and 235 healthy elders (HE) were deemed eligible and included in our
      meta-analysis. Every type of sleep disturbance was present in our studies with
      significant differences in the MCI subtypes. Compared with HE, overall MCI
      patients as a group expressed more SL and less SE; MCI patients showed less TST
      and SE and more SL and CAP; patients with amnestic mild cognitive impairment
      (aMCI) had less AI; patients with non-amnestic mild cognitive impairment (naMCI)
      had more TST and less AI. Patients with naMCI expressed more AI than those with
      aMCI. The results indicate that MCI patients might experience more serious sleep
      disturbance and that different MCI subtypes have different patterns of sleep
      disturbance.

PMID- 28455769
TI  - High asymmetric dimethylarginine, symmetric dimethylarginine and L-arginine
      levels in migraine patients.
AB  - Experimental and clinical data strongly suggests that nitric oxide (NO) plays a
      pivotal role in migraine. This is also supported by studies of migraine induced
      by substances that release NO. NO is synthesized from L-arginine by endothelial
      NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is the major endogenous
      competitive inhibitor of NOS. Symmetric dimethylarginine (SDMA) is an inactive
      stereoisomer of ADMA. It may reduce NO production by competing with arginine for
      cellular uptake. The aim of this study was to measure the levels of ADMA, SDMA
      and L-arginine in migraine patients during the interictal period. One hundred
      migraine patients and 100 healthy volunteers were recruited. The patients were in
      the interictal period and classified into two groups as having migraine with aura
      and migraine without aura. Their serum ADMA, SDMA and L-arginine levels were
      measured by high-performance liquid chromotography (HPLC) method. ADMA, SDMA and
      L-arginine levels were significantly higher in migraine patients compared to the
      control group. But there was no difference between the patients with and without
      aura. These results suggest that NOS inhibitors and L-arginine/NO pathway plays
      an important role in migraine pathopysiology.

PMID- 28455770
TI  - Autism, epilepsy, and synaptopathies: a not rare association.
AB  - Autism spectrum disorders (ASD) are neurodevelopmental disorders typically
      diagnosed in childhood, characterized by core social dysfunction, rigid and
      repetitive behaviors, restricted interests, and abnormal sensorial sensitivity.
      ASD belong to multifactorial diseases: both genetic and environmental factors
      have been considered as potential risk factors for their onset. ASD are often
      associated with neurological conditions: the co-occurrence of epilepsy is well
      documented and there is also evidence of a higher prevalence of EEG abnormalities
      with 4-86% of individuals with ASD presenting epileptiform or not epileptiform
      EEG abnormalities. The presence of epilepsy in people with ASD may be determined
      by several structural alterations, genetic conditions, or metabolic dysfunctions,
      known to play a role in the emergence of both epilepsy and autism. The purpose of
      this article is to discuss precisely such latter cause of the autism-epilepsy
      association, focusing specifically on those "synaptic genes," whose mutation
      predisposes to both the diseases.

PMID- 28455771
TI  - Cadmium and zinc activate adaptive mechanisms in Nicotiana tabacum similar to
      those observed in metal tolerant plants.
AB  - MAIN CONCLUSION: Tobacco germinated and grew in the presence of high
      concentrations of cadmium and zinc without toxic symptoms. Evidence suggests that
      these ions are sequestered into the vacuole by heavy metal/H + exchanger
      mechanisms. Heavy metal hyperaccumulation and hypertolerance are traits shared by
      a small set of plants which show specialized physiological and molecular
      adaptations allowing them to accumulate and sequester toxic metal ions. Nicotiana
      tabacum was used to test its potential as a metal-accumulator in a glass house
      experiment. Seed germination was not affected in the presence of increasing
      concentrations of zinc and cadmium. Juvenile and adult plants could concentrate
      CdCl2 and ZnSO4 to levels exceeding those in the hydroponic growth medium and
      maintained or increased their leaf dry weight when treated with 0.5- or 1-mM
      CdCl2 or 1-mM ZnSO4 for 5 days. Accumulation of heavy metals did not affect the
      chlorophyll and carotenoid levels, while variable effects were observed in cell
      sap osmolarity. Heavy metal-dependent H+ transport across the vacuole membrane
      was monitored using quinacrine fluorescence quenching. Cadmium- or zinc-dependent
      fluorescence recovery revealed that increasing concentrations of heavy metals
      stimulated the activities of the tonoplast Cd2+ or Zn2+/H+ exchangers.
      Immunodetection of the V-ATPase subunits showed that the increased proton
      transport by zinc was not due to changes in protein amount. MTP1 and MTP4
      immunodetection and semiquantitative RT-PCR of NtMTP1, NtNRAMP1, and NtZIP1
      helped to identify the genes that are likely involved in sequestration of cadmium
      and zinc in the leaf and root tissue. Finally, we demonstrated that cadmium and
      zinc treatments induced an accumulation of zinc in leaf tissues. This study shows
      that N. tabacum possesses a hyperaccumulation response, and thus could be used
      for phytoremediation purposes.

PMID- 28455772
TI  - Ergonomics perspective for identifying and reducing internal operative flow
      disruption for laparoscopic urological surgery.
AB  - BACKGROUND: The aim of this study is to examine operative flow disruption that
      occurs inside the surgical field, (internal operative flow disruption (OFD)),
      during urological laparoscopies, and to relate those events to external
      ergonomics environment in terms of monitor location, level of instruments'
      handles, and location of surgical team members. According to the our best
      knowledge, this is the first study of its kind. METHODS: A combination of real
      and video-aided observational study was conducted in the operating rooms at
      hospitals in Australia and China. Brain storming sessions were first conducted to
      identify the main internal OFD events, and the observable reasons, potential
      external, and latent ergonomic factors were listed. A prospective observational
      study was then conducted. The observer's records and the related video records of
      internal surgical fields were analysed. Procedures were categorised into groups
      based on similarity in ergonomics environment. RESULTS: The mapping process
      revealed 39 types of internal OFD events resulted from six reasons. A total of 24
      procedures were selected and arranged into two groups, each with twelve
      procedures. Group A was carried out under satisfactory ergonomics environment,
      while Group B was conducted under unsatisfactory ergonomics environment. A total
      of 1178 OFD events were detected delaying the total observed operative times
      (2966 min) by 220 min (7.43%). Average OFD/h in group A was less than 15, while
      in group B about 29 OFD/h. CONCLUSION: There are two main latent ergonomics
      factors affecting the surgeon's performance; non-physiological posture and long
      period static posture. The delays and number of internal OFD were nearly doubled
      where procedures were conducted under unsatisfactory external ergonomics
      environment. Some events such as stopping operation and irrelevant conversations
      during long procedures may have a positive influence on the surgeon's
      performance.

PMID- 28455774
TI  - Applications of fusion-fluorescence imaging using indocyanine green in
      laparoscopic hepatectomy.
AB  - BACKGROUND: Indocyanine green (ICG)-fluorescence imaging has been developed for
      real-time identification of hepatic tumors and segmental boundaries during
      hepatectomy. Fusion ICG-fluorescence imaging (real-time visualization of
      pseudocolor-fluorescence signals on white-light color images) may serve as a
      reliable navigation tool especially in laparoscopic hepatectomy, in which gross
      inspection and palpation are limited. METHODS: The study population consisted of
      41 patients undergoing laparoscopic hepatectomy. Hepatic tumors were identified
      by fluorescence imaging following the preoperative intravenous administration of
      ICG (0.5 mg/kg body weight). To visualize hepatic perfusion and segmental
      boundaries, ICG (1.25 mg) was injected intravenously during surgery, following
      closure of the proximal portal pedicle. A laparoscopic imaging system, which
      enabled superimposition of the pseudocolor-fluorescence images on white color
      images, was used for the fusion ICG-fluorescence imaging. RESULTS: Among the 53
      malignant tumors resected, fusion ICG-fluorescence imaging revealed 45 nodules
      (85%), including three nodules of colorectal liver metastasis unidentifiable by
      white-light color images or intraoperative ultrasonography. It also delineated
      the segmental boundaries on the hepatic raw surfaces as well as on the
      phrenic/visceral surfaces in all 12 patients evaluated using this technique.
      CONCLUSIONS: Fusion imaging enhances the feasibility of intraoperative ICG
      fluorescence imaging in the identification of hepatic tumors and segmental
      boundaries. It may therefore help surgeons in the safe and accurate completion of
      laparoscopic hepatectomies.

PMID- 28455773
TI  - Laparoscopy may decrease morbidity and length of stay after elective colon cancer
      resection, especially in frail patients: results from an observational real-life
      study.
AB  - BACKGROUND: Advantages of laparoscopic approach in colon cancer surgery have been
      previously demonstrated in controlled, randomized trials and in retrospective
      analysis of large administrative databases. Nevertheless, evidence of these
      advantages in prospective, observational studies from real-life settings is
      scarce. METHODS: This is a prospective, observational study, including a
      consecutive series of patients that underwent elective colonic resection for
      cancer in 52 Spanish hospitals. Pre-/intraoperative data, related to patient,
      tumor, surgical procedure, and hospital, were recorded as well as 60-day post
      operative outcomes, including wound infection, complications, anastomotic leak,
      length of stay, and mortality. A univariate and multivariate analysis was
      performed to determine the influence of laparoscopy on short-term post-operative
      outcome. A sub-analysis of the effect of laparoscopy according to patients' pre
      operative risk (ASA Score I-II vs. III-IV) was also performed. RESULTS: 2968
      patients were included: 44.2% were initially operated by laparoscopy, with a
      13.9% conversion rate to laparotomy. At univariate analysis, laparoscopy was
      associated with a decreased mortality (p = 0.015), morbidity (p < 0.0001), wound
      infection (p < 0.0001), and post-operative length of stay (p < 0.0001). At
      multivariate analysis, laparoscopy resulted as an independent protective factor
      for morbidity (OR 0.7; p = 0.004), wound infection (OR 0.6; p < 0.0001), and
      length of post-operative stay (Effect-2 days; p < 0.0001), compared to open
      approach. These advantages were more relevant in high-risk patients (ASA III-IV),
      even if the majority of them were operated by open approach (67.1%). CONCLUSIONS:
      In a real-life setting, laparoscopy decreases wound infection rate, post
      operative complications, and length of stay, especially in ASA III-IV patients.

PMID- 28455775
TI  - Surgical tuition within Irish hospitals: a national survey.
AB  - INTRODUCTION: The General Medical Council (GMC) of the UK states that doctors
      have a duty to train and contribute to the education of colleagues, and that
      those involved in formal clinical teaching should have a teaching qualification.
      OBJECTIVES: We sought to evaluate the current levels of engagement of surgical
      trainees and recently appointed surgical consultants in clinical teaching.
      METHODS: All trainees who commenced a basic or higher surgical training post
      during or after 2007 were invited to participate. The electronic questionnaire
      was administered using the survey tool GetFeedback, collecting information
      regarding subspecialty, current role, quantity of teaching that respondents
      engaged in and who they taught and teaching motivations and barriers. RESULTS:
      There were 128 respondents out of 358 invitations to participate (36% response
      rate). Less than half (39%) of respondents had attended formal courses on
      clinical education. Over 70% of respondents engaged in clinical teaching for two
      or more hours each week. A lack of time and resources were noted as barriers to
      engaging in teaching. We found a low number of those involved in teaching seeking
      feedback after teaching sessions. CONCLUSION: In surgery, the apprenticeship
      model is still the framework for developing the surgeons of the future. In
      attempting to produce a highly skilled workforce for the future, we rely on those
      in senior positions to train those coming through; higher surgical trainees are
      relied on to teach the core surgical trainees and so on. Our study shows a low
      level of formalisation of this model.

PMID- 28455776
TI  - The significance of regression in thin melanoma of the skin.

PMID- 28455777
TI  - Insights into Nano- and Micron-Scale Phase Separation in Amorphous Solid
      Dispersions Using Fluorescence-Based Techniques in Combination with Solid State
      Nuclear Magnetic Resonance Spectroscopy.
AB  - PURPOSE: Miscibility between the drug and the polymer in an amorphous solid
      dispersion (ASD) is considered to be one of the most important factors impacting
      the solid state stability and dissolution performance of the active
      pharmaceutical ingredient (API). The research described herein utilizes emerging
      fluorescence-based methodologies to probe (im)miscibility of itraconazole (ITZ)
      hydroxypropyl methylcellulose (HPMC) ASDs. METHODS: The ASDs were prepared by
      solvent evaporation with varying evaporation rates and were characterized by
      steady-state fluorescence spectroscopy, confocal imaging, differential scanning
      calorimetry (DSC), and solid state nuclear magnetic resonance (ssNMR)
      spectroscopy. RESULTS: The size of the phase separated domains for the ITZ-HPMC
      ASDs was affected by the solvent evaporation rate. Smaller domains (<10 nm) were
      observed in spray-dried ASDs, whereas larger domains (>30 nm) were found in ASDs
      prepared using slower evaporation rates. Confocal imaging provided visual
      confirmation of phase separation along with chemical specificity, achieved by
      selectively staining drug-rich and polymer-rich phases. ssNMR confirmed the
      results of fluorescence-based techniques and provided information on the size of
      phase separated domains. CONCLUSIONS: The fluorescence-based methodologies proved
      to be sensitive and rapid in detecting phase separation, even at the nanoscale,
      in the ITZ-HPMC ASDs. Fluorescence-based methods thus show promise for
      miscibility evaluation of spray-dried ASDs.

PMID- 28455778
TI  - On the Role of Mining Exposure in Epigenetic Effects in Parkinson's Disease.
AB  - To explore the possible influence of heavy metal mining on incidence of
      Parkinson's disease (PD), global DNA methylation was assessed in blood samples
      from a population of PD patients (n = 45) and control subjects (n = 52) in
      Antofagasta neighborhood, a Chilean city built for exclusive use of mining
      companies. Comparisons were made with PD subjects (n = 52) and control subjects
      (n = 59) from Santiago Chile, a city having little association with mining. All
      subjects were assessed by two neurologists and PD diagnosis was based on UK
      Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria. From blood
      samples obtained from each individual, a decrease in global DNA methylation was
      observed in PD patients either exposed (49% of control, P < 0.001) or not exposed
      (47% of control, P < 0.001) to mining activity. Although there was no difference
      in levels of DNA methylation between PD patients from the two cities, there was a
      lower level of DNA methylation in control subjects from Santiago versus
      Antofagasta.

PMID- 28455779
TI  - Microvascular reactivity measured by vascular occlusion test is an independent
      predictor for postoperative bleeding in patients undergoing cardiac surgery.
AB  - The purpose of the study is to investigate the relationship between microvascular
      reactivity and postoperative bleeding in cardiac surgery. The authors
      retrospectively analyzed a prospectively collected registry of cardiac surgery
      patients. Data from 154 patients enrolled in the registry were analyzed. A linear
      mixed model was performed to evaluate the association between the amount of
      postoperative chest tube output (CTO, milliliter, repeatedly measured at 0-8, 8
      24, and 24-48 h) and tissue oxygen saturation (StO2) recovery slope (%/s)
      measured by vascular occlusion test (VOT) at skin closure. A logistic regression
      was carried out to see the relationship between StO2 recovery slope and packed
      red blood cell (PRBC) transfusion during the 48-h postoperative period. In the
      multivariable adjusted model, the effect of StO2 recovery slope on postoperative
      CTO (log-transformed) was statistically significant, and the degree of StO2
      recovery slope was inversely related to the amount of CTO (exp(estimate) = 0.935;
      exp(95% CI) 0.881-0.992; p = 0.027). StO2 recovery slope was also inversely
      associated with postoperative PRBC transfusion possibility (OR = 0.795; 95% CI
      0.633-0.998; p = 0.048). Microvascular reactivity measured by VOT is
      independently and inversely associated with postoperative bleeding in patients
      undergoing cardiac surgery.

PMID- 28455780
TI  - Increase of circulating endocan over sepsis follow-up is associated with
      progression into organ dysfunction.
AB  - How circulating inflammatory mediators change upon sepsis progression has not
      been studied. We studied the follow-up changes of circulating vasoactive peptides
      and cytokines until the improvement or the worsening of a patient and progression
      into specific organ dysfunctions. In a prospective study, concentrations of tumor
      necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, IL-10, interferon
      gamma (IFNgamma), endocan and angiopoietin-2 (Ang-2) were measured in serum by an
      enzyme immunoassay in 175 patients at baseline; this was repeated within 24 h
      upon progression into new organ dysfunction (n = 141) or improvement (n = 34).
      Endocan and Ang-2 were the only parameters that were significantly increased
      among patients who worsened. Any increase of endocan was associated with
      worsening with odds ratio 16.65 (p < 0.0001). This increase was independently
      associated with progression into acute respiratory distress syndrome (ARDS) as
      shown after logistic regression analysis (odds ratio 2.91, p: 0.002). Changes of
      circulating cytokines do not mediate worsening of the critically ill patients.
      Instead endocan and Ang2 are increased and this may be interpreted as a key
      playing role in the pathogenesis of ARDS and septic shock. Any increase of
      endocan is a surrogate of worsening of the clinical course.

PMID- 28455781
TI  - Reduction in fecal microbiota diversity and short-chain fatty acid producers in
      Methicillin-resistant Staphylococcus aureus infected individuals as revealed by
      PacBio single molecule, real-time sequencing technology.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) may cause potentially lethal
      infections. Increasing evidence suggests that the gut microbiota is associated
      with human health. Yet, whether patients with MRSA infections carry specific
      signatures in their fecal microbiota composition has not been determined. Thus,
      this study aimed to compare the fecal microbiota profile of MRSA-positive
      patients (n=15) with individuals without MRSA infection (n=15) by using the
      PacBio single molecule, real-time (SMRT) DNA sequencing system and real-time
      quantitative polymerase chain reaction (qPCR). Mann-Whitney tests and unweighted
      UniFrac principal coordinate analysis (PCoA) showed that the profile of fecal
      microbiota was apparently different between the two populations. Both the
      community richness and diversity were reduced in the MRSA-positive group
      (p<0.050). The genera Acinetobacter and Enterococcus were highly enriched in the
      MRSA-positive group, whereas less short-chain fatty acid (SCFA)-producing
      bacteria, including Butyricimonas, Faecalibacterium, Roseburia, Ruminococcus,
      Megamonas and Phascolarctobacterium, were detected in the MRSA-positive group. At
      species level, the species Acinetobacter baumannii and Bacteroides
      thetaiotaomicron were prevalent in the MRSA-positive group, whereas opposite
      trends were observed in 17 other species, such as Faecalibacterium prausnitzii,
      Lactobacillus rogosae, Megamonas rupellensis and Phascolarctobacterium faecium.
      Positive correlations were observed between Acinetobacter baumannii and
      erythrocyte sedimentation rate (ESR) (R=0.554, p=0.001), as well as
      hypersensitive C reactive protein (hsCRP) (R=0.406, p=0.026). Faecalibacterium
      prausnitzii was negatively associated with ESR (R=-0.545, p=0.002), hsCRP (R=
      0.401, p=0.028) and total bile acids (TBA) (R=-0.364, p=0.048). In conclusion,
      the fecal microbiota structure was different between MRSA-positive and -negative
      patients. The increase in potential pathogens with the reduction of beneficial
      populations, such as SCFA-producing bacteria, in MRSA-positive patients may
      affect prognosis.

PMID- 28455782
TI  - RPC4046, A Novel Anti-interleukin-13 Antibody, Blocks IL-13 Binding to IL-13
      alpha1 and alpha2 Receptors: A Randomized, Double-Blind, Placebo-Controlled, Dose
      Escalation First-in-Human Study.
AB  - INTRODUCTION: A unique anti-interleukin (IL)-13 monoclonal antibody, RPC4046, was
      generated on the basis of differential IL-13 receptor (R) blockade as assessed in
      a murine asthma model; the safety, tolerability, pharmacokinetics, and
      pharmacodynamics of RPC4046 were evaluated in a first-in-human study. METHODS:
      Anti-IL-13 antibodies with varying receptor blocking specificity were evaluated
      in the ovalbumin-induced murine asthma model. A randomized, double-blind, placebo
      controlled, dose-escalation first-in-human study (NCT00986037) was conducted with
      RPC4046 in healthy adults and patients with mild to moderate controlled asthma.
      RESULTS: In the ovalbumin model, blocking IL-13 binding to both IL-13Rs (IL
      13Ralpha1 and IL-13Ralpha2) inhibited more asthma phenotypic features and more
      fully normalized the distinct IL-13 gene transcription associated with asthma
      compared with blocking IL-13Ralpha1 alone. In humans, RPC4046 exposure increased
      dose-dependently; pharmacokinetics were similar in healthy and asthmatic
      subjects, and blockade of both IL-13Rs uniquely affected IL-13 gene
      transcription. A minority of participants (28%) had antidrug antibodies, which
      were transient and appeared not to affect pharmacokinetics. Adverse event
      profiles were similar in healthy and asthmatic subjects, without dose-related or
      administration route differences, systemic infusion-related reactions, or asthma
      symptom worsening. Adverse events were mild to moderate, with none reported as
      probably related to RPC4046 or leading to discontinuations. Non-serious upper
      respiratory tract infections were more frequent with RPC4046 versus placebo.
      CONCLUSION: RPC4046 is a novel anti-IL-13 antibody that blocks IL-13 binding to
      both receptors and more fully blocks the asthma phenotype. These results support
      further investigation of RPC4046 for IL-13-related allergic/inflammatory diseases
      (e.g., asthma and eosinophilic esophagitis). FUNDING: AbbVie Inc. sponsored the
      studies and contributed to the design and conduct of the studies, data
      management, data analysis, interpretation of the data, and in the preparation and
      approval of the manuscript.

PMID- 28455783
TI  - Management of Grass Pollen Allergy with 5-Grass Pollen Tablet: Results of a 2
      Year Real-Life Study.
AB  - INTRODUCTION: Allergen immunotherapy is the only treatment option for allergic
      rhinitis with disease-altering potential. It was the objective of this study to
      assess the effectiveness and tolerability of a 5-grass pollen tablet in a large
      population of non-selected grass pollen allergic patients, i.e. patients with
      different clinical profiles in daily clinical practice. METHODS: In a 2-year,
      prospective, open-label, multicenter, non-controlled, observational study
      patients were included from 327 centers across Germany. Rhinoconjunctivitis
      symptoms, symptomatic medication intake and adverse events were recorded.
      RESULTS: A total of 1482 patients aged 4-75 years were included. During the 2
      year period of 5-grass pollen tablet therapy, mean rhinoconjunctivitis score
      decreased significantly in the overall study population by 65.5% (P < 0.001). The
      percentage of patients taking symptomatic medication decreased from 83.8% to
      42.7%. Mean 2-year improvements in rhinoconjunctivitis scores and decreases in
      the percentage of patients taking symptomatic medication were broadly similar in
      adults, adolescents and children, in patients with polyallergy versus
      monoallergy, and in patients with/without asthma. Among polyallergic patients,
      concomitant application of another specific immunotherapy did not impair
      treatment outcomes. Adverse drug reactions, predominantly affecting the local
      application area, occurred in 15.4% of the overall patient population (n = 229).
      No cases of anaphylaxis or epinephrine use were documented. CONCLUSION: This
      study indicates that sublingual immunotherapy with the 5-grass pollen tablet is
      well tolerated and provides sustained effectiveness over 2 years in patients with
      different clinical profiles, producing a significant decrease in allergic
      symptoms and a reduction in the use of symptomatic medication. FUNDING:
      Stallergenes GmbH.

PMID- 28455784
TI  - Clinical Features of Patients with Diffuse Alveolar Hemorrhage due to Negative
      Pressure Pulmonary Edema.
AB  - PURPOSE: Diffuse alveolar hemorrhage (DAH) with negative-pressure pulmonary edema
      (NPPE) is an uncommon yet life-threatening condition. We aimed at describing the
      circumstances, clinical, radiological, and bronchoscopic features, as well as the
      outcome of patients with NPPE-related DAH. METHODS: We performed a retrospective,
      observational cohort study, using data prospectively collected over 35 years in
      an intensive care unit (ICU). RESULTS: Of the 149 patients admitted for DAH, we
      identified 18 NPPE episodes in 15 patients, one admitted four times for recurrent
      NPPE-related DAH. The patients were primarily young, male, and athletic. The NPPE
      setting was postoperative (n = 12/18, 67%) or following generalized tonic-clonic
      seizures (n = 6/18, 33%). Hemoptysis was almost constant (n = 17/18, 94%), yet
      rarely massive (>200 cc, n = 1/18, 6%), with anemia observed in 10 (56%)
      episodes. The DAH triad (hemoptysis, anemia, and pulmonary infiltrates) was
      observed in 50% of episodes (n = 9/18), and acute respiratory failure in 94% (n =
      17/18). Chest computed tomography revealed diffuse bilateral ground glass
      opacities (n = 10/10, 100%), while bronchoscopy detected bilateral hemorrhage (n
      = 12/12, 100%) and macroscopically bloody bronchoalveolar lavage, with
      siderophage absence in most (n = 7/8, 88%), indicating acute DAH. While one
      episode proved fatal, the other 17 recovered rapidly, with a mean ICU stay
      lasting 4.6 (2-15) days. Typically, the evolution was rapidly favorable under
      supportive care. CONCLUSION: NPPE-related DAH is a rare life-threatening
      condition occurring primarily after tonic-clonic generalized seizure or
      generalized anesthesia. Clinical circumstances are a key to its diagnosis. Early
      diagnosis and recognition likely allow for successful management of this
      potentially serious complication, whereas ictal-DAH appears ominous in epileptic
      patients.

PMID- 28455785
TI  - Hypertonic Saline as a Useful Tool for Sputum Induction and Pathogen Detection in
      Cystic Fibrosis.
AB  - PURPOSE: The aim of this study was to compare the qualitative and semi
      quantitative detection of pathogens in the airway secretions of patients with
      cystic fibrosis (CF) and the sputum induction capacity before and after
      inhalation of 7% hypertonic saline solution (HSS). METHODS: The study enrolled 64
      patients with CF. Airway secretions were collected from all enrolled patients
      with CF before and after inhalation of 7% HSS, and the samples were screened for
      pathogens. RESULTS: Inhalation of 7% HSS increased the probability of producing
      sputum from 36 to 52% (p = 0.002) in children with CF. The effect was most in
      children under 11 years. Inhalation of 7% HSS improved qualitative pathogen
      identification (p = 0.008). Inhalation of 7% HSS increased the mucoid Pseudomonas
      aeruginosa (p = 0.002) and non-mucoid P. aeruginosa in the semi-quantitative
      analysis (p = 0.035). Four new pathogens (Aspergillus fumigatus, Achromobacter
      xylosoxidans, Ochrobactrum anthropi, and Elizabethkingia meningoseptica) were
      identified in the sputum samples collected from the airways of patients with CF
      following 7% HSS. CONCLUSIONS: Inhalation of 7% HSS increased sputum production
      and pathogen identification in children with CF. The inhalation of 7% HSS was
      feasible and should be implemented for routine pathogen detection in the airways
      of patients with CF, particularly in those patients who do not produce sputum.

PMID- 28455786
TI  - Individual Impact Magnitude vs. Cumulative Magnitude for Estimating Concussion
      Odds.
AB  - Helmeted impact devices have allowed researchers to investigate the biomechanics
      of head impacts in vivo. While increased impact magnitude has been associated
      with greater concussion risk, a definitive concussive threshold has not been
      established. It is likely that concussion risk is not determined by a single
      impact itself, but a host of predisposing factors. These factors may include
      genetics, fatigue, and/or prior head impact exposure. The objective of the
      current paper is to investigate the association between cumulative head impact
      magnitude and concussion risk. It is hypothesized that increased cumulative
      magnitudes will be associated with greater concussion risk. This retrospective
      analysis included participants that were recruited from regional high-schools in
      Illinois and Michigan from 2007 to 2014 as part of an ongoing study on concussion
      biomechanics. Across seven seasons, 185 high school football athletes were
      instrumented with the Head Impact Telemetry system. Out of 185 athletes, 31 (17%)
      sustained a concussion, with two athletes sustaining two concussions over the
      study period, yielding 33 concussive events. The system recorded 78,204 impacts
      for all concussed players. Linear acceleration, rotational acceleration, and head
      impact telemetry severity profile (HITsp) magnitudes were summed within five
      timeframes: the day of injury, three days prior to injury, seven days prior to
      injury, 30 days prior to injury, and prior in-season exposure. Logistic
      regressions were modeled to explain concussive events based on the singular
      linear acceleration, rotational acceleration, and HITsp event along with the
      calculated summations over time. Linear acceleration, rotational acceleration,
      and HITsp all produced significant models estimating concussion (p < 0.05). The
      strongest estimators of a concussive impact were the linear acceleration (OR =
      1.040, p < 0.05), rotational acceleration (OR = 1.001, p < 0.05), and HITsp (OR =
      1.003, p < 0.05) for the singular impact rather than any of the cumulative
      magnitude calculations. Moreover, no cumulative count measure was significant for
      linear or rotational acceleration. Results from this investigation support the
      growing literature indicating cumulative magnitude is not related to concussion
      likelihood. Cumulative magnitude is a simplistic measure of the total exposure
      sustained by a player over a given period. However, this measure is limited as it
      assumes the brain is a static structure unable to undergo self-repair. Future
      research should consider how biological recovery between impacts may influence
      concussion risk.

PMID- 28455787
TI  - Elevated Expression of TRPC4 in Cortical Lesions of Focal Cortical Dysplasia II
      and Tuberous Sclerosis Complex.
AB  - Focal cortical dysplasia type II (FCD II) and tuberous sclerosis complex (TSC)
      are well-known causes of chronic refractory epilepsy in children. Canonical
      transient receptor potential channels (TRPCs) are non-selective cation channels
      that are commonly activated by phospholipase C (PLC) stimulation. Previous
      studies found that TRPC4 may participate in the process of epileptogenesis. This
      study aimed to examine the expression and distribution of TRPC4 in FCD II (n =
      24) and TSC (n = 11) surgical specimens compared with that in age-matched autopsy
      control samples (n = 12). We found that the protein levels of TRPC4 and its
      upstream factor, PLC delta 1 (PLCD1), were elevated in FCD II and TSC samples
      compared to those of control samples. Immunohistochemistry assays revealed that
      TRPC4 staining was stronger in malformed cells, such as dysmorphic neurons,
      balloon cells and giant cells. Moderate-to-strong staining of the upstream factor
      PLCD1 was also identified in abnormal neurons. Moreover, double
      immunofluorescence staining revealed that TRPC4 was colocalised with
      glutamatergic and GABAergic neuron markers. Taken together, our results indicate
      that overexpression of TRPC4 protein may be involved in the epileptogenesis of
      FCD II and TSC.

PMID- 28455788
TI  - Diagnosis and treatment patterns for patients with leptomeningeal metastasis from
      solid tumors across Europe.
AB  - Leptomeningeal metastases are a late manifestation of systemic cancer which
      affects up to 10% of patients with solid tumors. Prognosis is poor, and overall
      survival at 1 year is only approximately 10%. Management depends mainly on
      general and neurological condition, primary tumor, and patterns of metastasis,
      notably absence or presence of concurrent systemic or solid brain metastases.
      Here we set out to characterize current practice patterns of diagnosis and
      treatment of patients with leptomeningeal metastasis in Europe. We prepared a web
      based survey including 25 simple or multiple choices questions on best practice
      supplemented by eight case vignettes with various diagnosis and management
      options. The survey was sent to the membership of the European Association of
      Neuro-Oncology and the European Organisation for Research and Treatment of Cancer
      Brain Tumor Group. Between April 7, 2016 and August 8, 2016, 224 colleagues from
      26 countries initiated the survey, 115 colleagues completed the whole survey.
      There were major differences both in the general diagnostic and therapeutic
      approach, e.g., regarding the use of cerebrospinal fluid (CSF) flow studies,
      intra-CSF chemotherapy, various types of radiotherapy, and even more so when
      selecting decisions on diagnostic and therapeutic measures for single case
      vignettes. Diagnosis and treatment decisions for patients with leptomeningeal
      metastasis from solid tumors vary widely across Europe. Standardization of
      diagnosis and evaluation tools as well as controlled studies to improve the level
      of evidence for all therapeutic approaches to LM are required.

PMID- 28455789
TI  - Functional and structural consequences of chemokine (C-X-C motif) receptor 4
      activation with cognate and non-cognate agonists.
AB  - Chemokine (C-X-C motif) receptor 4 (CXCR4) regulates cell trafficking and plays
      important roles in the immune system. Ubiquitin has recently been identified as
      an endogenous non-cognate agonist of CXCR4, which activates CXCR4 via interaction
      sites that are distinct from those of the cognate agonist C-X-C motif chemokine
      ligand 12 (CXCL12). As compared with CXCL12, chemotactic activities of ubiquitin
      in primary human cells are poorly characterized. Furthermore, evidence for
      functional selectivity of CXCR4 agonists is lacking, and structural consequences
      of ubiquitin binding to CXCR4 are unknown. Here, we show that ubiquitin and
      CXCL12 have comparable chemotactic activities in normal human peripheral blood
      mononuclear cells, monocytes, vascular smooth muscle, and endothelial cells.
      Chemotactic activities of the CXCR4 ligands could be inhibited with the selective
      CXCR4 antagonist AMD3100 and with a peptide analogue of the second transmembrane
      domain of CXCR4. In human monocytes, ubiquitin- and CXCL12-induced chemotaxis
      could be inhibited with pertussis toxin and with inhibitors of phospholipase C,
      phosphatidylinositol 3 kinase, and extracellular signal-regulated kinase 1/2.
      Both agonists induced inositol trisphosphate production in vascular smooth muscle
      cells, which could be inhibited with AMD3100. In beta-arrestin recruitment
      assays, ubiquitin did not sufficiently recruit beta-arrestin2 to CXCR4 (EC50 > 10
      MUM), whereas the EC50 for CXCL12 was 4.6 nM (95% confidence interval 3.1-6.1
      nM). Both agonists induced similar chemical shift changes in the 13C-1H
      heteronuclear single quantum correlation (HSQC) spectrum of CXCR4 in membranes,
      whereas CXCL11 did not significantly alter the 13C-1H-HSQC spectrum of CXCR4. Our
      findings point towards ubiquitin as a biased agonist of CXCR4.

PMID- 28455790
TI  - Advanced glycation end products attenuate the function of tumor necrosis factor
      like weak inducer of apoptosis to regulate the inflammatory response.
AB  - Advanced glycation end products (AGEs) are formed from the non-enzymatic
      glycation reaction of reducing sugars or their metabolites with the free amino
      groups of several biomolecules and are known to play pathophysiological roles in
      various inflammatory diseases. In an earlier study, it was suggested that tumor
      necrosis factor-like weak inducer of apoptosis (TWEAK) has a unique role to
      regulate the tumor necrosis factor alpha (TNFalpha)-induced inflammatory
      response. In this study, we investigated the effect of the AGEs-TWEAK interaction
      on proinflammatory signaling responses in endothelial cells and the influence of
      AGEs on the cellular function of TWEAK in the inflammatory process. The effect of
      AGEs on the TWEAK/TNFalpha-induced gene expression of interleukin-8 (IL-8) was
      determined by real-time RT-PCR in endothelial-like EA.hy.926 cells. The pull-down
      assay was performed using recombinant His-tagged TWEAK and AGEs. The NF-kappaB
      activation was analyzed by Western blotting with canonical and non-canonical
      pathway-specific antibodies. AGEs dose-dependently inhibited TWEAK-induced IL-8
      gene expression, whereas AGEs themselves had almost no effect on IL-8 expression.
      AGEs were found to bind directly to TWEAK in the pull-down assay. TNFalpha
      induced IL-8 production and canonical NF-kappaB activation were suppressed by
      TWEAK pretreatment, whereas TWEAK-induced non-canonical NF-kappaB activation was
      enhanced by pretreatment. These effects induced by TWEAK pretreatment were
      abolished by the co-addition of AGEs. Our findings suggest that AGEs attenuate
      the function of TWEAK to regulate the TNFalpha-induced inflammatory responses,
      which provide important clues for understanding the significance of the AGEs
      TWEAK interaction in inflammatory processes.

PMID- 28455791
TI  - Resveratrol inhibits hepatocellular carcinoma progression driven by hepatic
      stellate cells by targeting Gli-1.
AB  - Hepatocellular carcinoma (HCC) is characterized by hypervascularity. Hepatic
      stellate cells (HSCs) play very important roles in HCC malignant progression, as
      these cells facilitate HCC tumorigenesis and metastasis. We demonstrated that
      HSCs induce angiogenesis in HCC by upregulating the expression of Gli-1, which
      stimulates reactive oxygen species (ROS) production and potentiates increases in
      HCC cell invasiveness. Resveratrol abolished HSC-induced angiogenesis and
      suppressed ROS production and IL-6 and CXCR4 receptor expression in HepG2 cells
      by down-regulating Gli-1 expression. These findings indicate that Gli-1 may be a
      target for the prevention of angiogenesis in HCC and that resveratrol may have
      beneficial effects with respect to preventing HCC progression.

PMID- 28455792
TI  - C14orf28 downregulated by miR-519d contributes to oncogenicity and regulates
      apoptosis and EMT in colorectal cancer.
AB  - C14orf28 [alias dopamine receptor-interacting protein (DRIP1)] is belonging to
      the family of DRIPs. However, the function of C14orf28 in cancer remains unclear.
      Herein, we found that C14orf28 was upregulated in colorectal cancer tissues
      compared to the adjacent non-tumor tissues. Overexpression of C14orf28 promoted
      the cellular proliferation, migration, invasion of colorectal cancer cells. In
      addition, C14orf28 inhibited apoptosis and promoted the EMT process. To explore
      the mechanism of dysregulation, C14orf28 was identified to be a target of miR
      519d by targeting its 3'UTR. Furthermore, in agreement, C14orf28 overexpression
      counteracted the inhibitory effect of miR-519d. Together, these results evidenced
      that C14orf28 downregulated by miR-519d contributes to tumorigenesis and might
      provide new potential targets for colorectal cancer therapy.

PMID- 28455793
TI  - Detecting Signals of Disproportionate Reporting from Singapore's Spontaneous
      Adverse Event Reporting System: An Application of the Sequential Probability
      Ratio Test.
AB  - INTRODUCTION: The ability to detect safety concerns from spontaneous adverse drug
      reaction reports in a timely and efficient manner remains important in public
      health. OBJECTIVE: This paper explores the behaviour of the Sequential
      Probability Ratio Test (SPRT) and ability to detect signals of disproportionate
      reporting (SDRs) in the Singapore context. METHODS: We used SPRT with a
      combination of two hypothesised relative risks (hRRs) of 2 and 4.1 to detect
      signals of both common and rare adverse events in our small database. We compared
      SPRT with other methods in terms of number of signals detected and whether
      labelled adverse drug reactions were detected or the reaction terms were
      considered serious. The other methods used were reporting odds ratio (ROR),
      Bayesian Confidence Propagation Neural Network (BCPNN) and Gamma Poisson Shrinker
      (GPS). RESULTS: The SPRT produced 2187 signals in common with all methods, 268
      unique signals, and 70 signals in common with at least one other method, and did
      not produce signals in 178 cases where two other methods detected them, and there
      were 403 signals unique to one of the other methods. In terms of sensitivity, ROR
      performed better than other methods, but the SPRT method found more new signals.
      The performances of the methods were similar for negative predictive value and
      specificity. CONCLUSIONS: Using a combination of hRRs for SPRT could be a useful
      screening tool for regulatory agencies, and more detailed investigation of the
      medical utility of the system is merited.

PMID- 28455795
TI  - Bayes factors for the linear ballistic accumulator model of decision-making.
AB  - Evidence accumulation models of decision-making have led to advances in several
      different areas of psychology. These models provide a way to integrate response
      time and accuracy data, and to describe performance in terms of latent cognitive
      processes. Testing important psychological hypotheses using cognitive models
      requires a method to make inferences about different versions of the models which
      assume different parameters to cause observed effects. The task of model-based
      inference using noisy data is difficult, and has proven especially problematic
      with current model selection methods based on parameter estimation. We provide a
      method for computing Bayes factors through Monte-Carlo integration for the linear
      ballistic accumulator (LBA; Brown and Heathcote, 2008), a widely used evidence
      accumulation model. Bayes factors are used frequently for inference with simpler
      statistical models, and they do not require parameter estimation. In order to
      overcome the computational burden of estimating Bayes factors via brute force
      integration, we exploit general purpose graphical processing units; we provide
      free code for this. This approach allows estimation of Bayes factors via Monte
      Carlo integration within a practical time frame. We demonstrate the method using
      both simulated and real data. We investigate the stability of the Monte-Carlo
      approximation, and the LBA's inferential properties, in simulation studies.

PMID- 28455794
TI  - The Montreal Protocol for Identification of Amusia.
AB  - The Montreal Battery for the Evaluation of Amusia (MBEA; Peretz, Champod, & Hyde
      Annals of the New York Academy of Sciences, 999, 58-75, 2003) is an empirically
      grounded quantitative tool that is widely used to identify individuals with
      congenital amusia. The use of such a standardized measure ensures that the
      individuals tested will conform to a specific neuropsychological profile,
      allowing for comparisons across studies and research groups. Recently, a number
      of researchers have published credible critiques of the usefulness of the MBEA as
      a diagnostic tool for amusia. Here we argue that the MBEA and its online
      counterpart, the AMUSIA tests (Peretz et al. Music Perception, 25, 331-343,
      2008), should be considered steps in a screening process for amusia, rather than
      standalone diagnostic tools. The goal of this article is to present, in detailed
      and easily replicable format, the full protocol through which congenital amusics
      should be identified. In providing information that has often gone unreported in
      published articles, we aim to clarify the strengths and limitations of the MBEA
      and to make recommendations for its continued use by the research community as
      part of the Montreal Protocol for Identification of Amusia.

PMID- 28455796
TI  - Effect of Brood Pheromone on Survival and Nutrient Intake of African Honey Bees
      (Apis mellifera scutellata) under Controlled Conditions.
AB  - The influence of pheromones on insect physiology and behavior has been thoroughly
      reported for numerous aspects, such as attraction, gland development,
      aggregation, mate and kin recognition. Brood pheromone (BP) is released by honey
      bee larvae to indicate their protein requirements to the colony. Although BP is
      known to modulate pollen and protein consumption, which in turn can affect
      physiological and morphological parameters, such as hypopharyngeal gland (HPG)
      development and ovarian activation, few studies have focused on the effect of BP
      on nutritional balance. In this study, we exposed newly emerged worker bees for
      14 d and found that BP exposure increased protein intake during the first few
      days, with a peak in consumption at day four following exposure. BP exposure
      decreased survival of caged honey bees, but did not affect either the size of the
      HPG acini or ovarian activation stage. The uncoupling of the BP releaser effect,
      facilitated by working under controlled conditions, and the presence of larvae as
      stimulating cues are discussed.

PMID- 28455797
TI  - The Fungus Raffaelea lauricola Modifies Behavior of Its Symbiont and Vector, the
      Redbay Ambrosia Beetle (Xyleborus Glabratus), by Altering Host Plant Volatile
      Production.
AB  - The redbay ambrosia beetle Xyleborus glabratus is the vector of the symbiotic
      fungus, Raffaelea lauricola that causes laurel wilt, a highly lethal disease to
      members of the Lauraceae family. Pioneer X. glabratus beetles infect live trees
      with R. lauricola, and only when tree health starts declining more X. glabratus
      are attracted to the infected tree. Until now this sequence of events was not
      well understood. In this study, we investigated the temporal patterns of host
      volatiles and phytohormone production and vector attraction in relation to laurel
      wilt symptomology. Following inoculations with R. lauricola, volatile collections
      and behavioral tests were performed at different time points. Three days after
      infection (DAI), we found significant repellency of X. glabratus by leaf odors of
      infected swamp bay Persea palustris as compared with controls. However, at 10 and
      20 DAI, X. glabratus were more attracted to leaf odors from infected than non
      infected host plants. GC-MS analysis revealed an increase in methyl salicylate
      (MeSA) 3 DAI, whereas an increase of sesquiterpenes and leaf aldehydes was
      observed 10 and 20 DAI in leaf volatiles. MeSA was the only behaviorally active
      repellent of X. glabratus in laboratory bioassays. In contrast, X. glabratus did
      not prefer infected wood over healthy wood, and there was no associated
      significant difference in their volatile profiles. Analyses of phytohormone
      profiles revealed an initial increase in the amount of salicylic acid (SA) in
      leaf tissues following fungal infection, suggesting that the SA pathway was
      activated by R. lauricola infection, and this activation caused increased release
      of MeSA. Overall, our findings provide a better understanding of X. glabratus
      ecology and underline chemical interactions with its symbiotic fungus. Our work
      also demonstrates how the laurel wilt pathosystem alters host defenses to impact
      vector behavior and suggests manipulation of host odor by the fungus that attract
      more vectors.

PMID- 28455798
TI  - Internal anal sphincter achalasia: data from a nationwide survey of allied
      disorders of Hirschsprung's disease in Japan.
AB  - PURPOSE: To investigate the incidence and treatment of internal anal sphincter
      achalasia (IASA) in Japan based on an analysis of data from a nationwide
      retrospective cohort study of the allied disorders of Hirschsprung's disease.
      METHODS: Five cases of definitive IASA were collected from a nationwide
      retrospective cohort study conducted from 2001 to 2010 and a search of the
      Japanese literature. RESULTS: Symptoms developed during the neonatal period in
      two patients, during early childhood in two, and at school age in one. Symptoms
      included abdominal distension with severe constipation (n = 4) and enterocolitis
      (n = 1). Rectocolonography showed megarectum and no narrow segment in most of the
      patients. All patients were negative for rectosphincteric reflex. The presence of
      ganglion cells was demonstrated by H&E or AChE staining from rectal mucosal
      biopsies or resected full-thickness segments. Two patients were treated
      conservatively, and three were treated surgically by internal anal sphincter
      myotomy (n = 2) or Lynn procedure (n = 1), with satisfactory outcomes.
      CONCLUSION: IASA is a rare but distinct entity in Japan. Although the clinical
      features of IASA resemble those of short- and ultrashort-segment HD,
      characteristic pathological findings include the presence of ganglion cells. The
      outcomes of both conservative and surgical treatment are good.

PMID- 28455799
TI  - Periarterial papaverine to treat renal artery vasospasm during robot-assisted
      laparoscopic partial nephrectomy.
AB  - Renal artery vasospasm can be a troublesome complication during robot-assisted
      laparoscopic partial nephrectomy. Urologists performing this procedure,
      especially if utilizing selective arterial vascular microdissection, should be
      aware of using papaverine for both prevention and treatment of renal artery
      vasospasm. We present a 33-year-old male who developed severe renal artery
      vasospasm just with hilar dissection causing the kidney to become ischemic.
      Papaverine was topically applied on the renal arteries resulting in vasodilation
      and reperfusion of the kidney. Our objective of this report is to raise awareness
      of this complication as well as to review the literature on periarterial
      papaverine use and the dosing for topical applications.

PMID- 28455800
TI  - Global trends in paediatric robot-assisted urological surgery: a bibliometric and
      Progressive Scholarly Acceptance analysis.
AB  - The inaugural robot-assisted urological procedure in a child was performed in
      2002. This study aims to catalogue the impact of this technology by utilizing
      bibliographic data as a surrogate measure for global diffusion activity and to
      appraise the quality of evidence in this field. A systematic literature search
      was performed to retrieve all reported cases of paediatric robot-assisted
      urological surgery published between 2003 and 2016. The status of scientific
      community acceptance was determined using a newly developed analysis model named
      progressive scholarly acceptance. A total of 151 publications were identified
      that reported 3688 procedures in 3372 patients. The most reported procedures were
      pyeloplasty (n = 1923) and ureteral reimplantation (n = 1120). There were 16
      countries and 48 institutions represented in the literature. On average, the
      total case volume reported in the literature more than doubled each year (mean
      value increase 236.6% per annum). The level of evidence for original studies
      remains limited to case reports, case series and retrospective comparative
      studies. Progressive Scholarly Acceptance charts indicate that robot-assisted
      techniques for pyeloplasty or ureteral reimplantation are yet to be accepted by
      the scientific community. Global adoption trends for robotic surgery in
      paediatric urology have been progressive but remain low volume. Pyeloplasty and
      ureteral reimplantation are dominant applications. Robot-assisted techniques for
      these procedures are not supported by high quality evidence at present. Next
      generation robots are forecast to be smaller, cheaper, more advanced and
      customized for paediatric patients. Ongoing critical evaluation must occur
      simultaneously with expected technology evolution.

PMID- 28455801
TI  - Weight Loss Failure and Reoperation After Laparoscopic Adjustable Gastric Banding
      and Gastric Bypass: a Case-Matched Cohort Study.
AB  - INTRODUCTION: Not long ago, laparoscopic adjustable gastric banding (LAGB) was
      considered a safe and effective treatment of morbid obesity; however, long-term
      outcomes revealed significant complication and failure rates. We hypothesized
      that LAGB has higher rates of weight loss failure, reoperation, and overall
      failure compared to laparoscopic gastric bypass (LRYGB) at long-term follow-up.
      METHODS: A matched case-control study was performed. Patients who underwent
      primary LAGB or LRYGB at a university hospital between 2004 and 2011 were
      propensity matched for age, gender, race, body mass index (BMI), and weight
      related co-morbidities. Outcomes included demographics, percent excess weight
      loss (% EWL) and reoperation, weight loss failure (<50% EWL), and overall failure
      (procedure-related reoperation and/or <50% EWL) at 3- and 5-year follow-up.
      RESULTS: In all, 228 LAGB and 228 LRYGB patients matched. LAGB patients had less
      mean EWL at 3 years (35 vs. 71%, P < 0.05) and 5 years (29.3 vs. 66.7%, P <
      0.05). LAGB (11%) and LRYGB (11.5%) patients required procedure-related
      reoperation. More LAGB patients suffered weight loss failure at 3 years (75 vs.
      10.5%, P < 0.05) and 5 years (81.5 vs. 15.4%, P < 0.05). Overall failure rates
      were higher after LAGB. The most common complication after LAGB was
      pouch/esophageal enlargement (9.7%) and after LRYGB was internal hernia (4.8%).
      LAGB patients had higher morbidity (19 vs. 12.7%, P = 0.04) but similar procedure
      related mortality (0 vs. 0.4%). CONCLUSIONS: LAGB has significantly higher rates
      of weight loss failure compared to LRYGB with similar rates of procedure-related
      reoperation. Overall failure rates are higher after LAGB. These data suggest the
      long-term effectiveness of LAGB might be limited.

PMID- 28455802
TI  - Gastroesophageal Reflux Disease After Laparoscopic Sleeve Gastrectomy with
      Concomitant Hiatal Hernia Repair: an Unresolved Question.
AB  - PURPOSE: The effectiveness of the concomitant repair of hiatal hernia (HHR)
      during laparoscopic sleeve gastrectomy (LSG) in reducing gastroesophageal reflux
      disease (GERD) symptoms is still unclear. The aim of this study is to assess the
      effect of concomitant HHR on postoperative GERD symptoms in our patient
      population. MATERIALS AND METHODS: A retrospective review of patients who
      underwent LSG with or without HHR between 2011and 2014 was performed. Pre- and
      postoperative GERD symptoms were assessed at different time intervals until a
      maximum of 2 years after the surgery. RESULTS: The study included 165 patients;
      76 (46%) underwent LSG with concomitant HHR (group A) while the rest underwent
      only LSG (group B). Baseline GERD complaints were more prevalent in group A (61.8
      vs 41.6%, p = 0.04), in which 44 patients (57.9%) had evidence of hiatal hernia
      on preoperative EGD. In the remaining 32 patients, it was diagnosed
      intraoperatively. GERD symptoms did not significantly differ between the two
      groups after years 1 and 2. GERD remission was observed in 21.3% of the 76
      patients who underwent concomitant HHR (group A) and in 29.7% of those who did
      not (group B) while new-onset GERD symptoms were reported in 12 patients (41.4%)
      in group A and in 24 patients (46.2%) in group B. CONCLUSIONS: Routine HHR at the
      time of LSG does not show an improvement in GERD symptoms. More prospective
      studies are needed to clarify the role of the routine dissection, identification,
      and repair of concomitant hiatal hernia during LSG.

PMID- 28455803
TI  - Experience with an Enhanced Recovery After Surgery (ERAS) Program for Bariatric
      Surgery: Comparison of MGB and LSG in 374 Patients.
AB  - BACKGROUND: Strategic multidisciplinary protocols for "enhanced recovery after
      surgery" (ERAS) have demonstrated reductions in length of hospital stay (LOS),
      morbidity, and costs in conjunction with bariatric procedures. METHODS: We
      prospectively investigated the effectiveness and safety of an ERAS protocol with
      laparoscopic omega loop gastric bypass ("mini" gastric bypass, MGB) and LSG in
      morbidly obese patients. RESULTS: Average LOS was 1.24 days (range 1-14); 86.1%
      discharged on day 1; 96.9% by day 2, a value comparable or better than that of
      other ERAS studies vs standard care according to meta-analysis. Complications
      2.9%; readmission 2.1%; reintervention 1.3%. CONCLUSION: The program was equally
      safe with both procedures. Postoperative antithrombotic heparin does not appear
      necessary in low-risk patients. Bariatric surgical ERAS programs are evolving and
      not yet standardized.

PMID- 28455804
TI  - Microbial Catalyzed Regio-Selective Demethylation of Colchicine by Streptomyces
      griseus ATCC 13273.
AB  - Colchicinoids and their derivatives are of great importance in pharmaceutical
      applications, and colchicine is usually used as the first choice for the
      treatment of gout. To expand the structural diversities and clinical application
      of colchicinoids, many attempts have been established for the derivatives with
      better activity or less toxicity. Herein, in this paper, we report a direct
      microbial transformation of colchicine into 2-O-demethyl-colchicine (M1) and 3-O
      demethl-colchicine (M2) by Streptomyces griseus ATCC 13273. It is noteworthy that
      when DMF was used as co-solvent, the yield of M1 and M2 could reach up to 51 and
      31%, respectively. All the structures of the metabolites were elucidated
      unambiguously by ESI-MS, 1H-NMR, 13C-NMR, and 2D-NMR spectroscopy.

PMID- 28455805
TI  - The Influence of Different Strategies for the Saccharification of the Banana
      Plant Pseudostem and the Detoxification of Concentrated Broth on Bioethanol
      Production.
AB  - Pseudostem of the Musa cavendishii banana plant was submitted to chemical
      pretreatments with acid (H2SO4 2%, 120  degrees C, 15 min) and with alkali (NaOH
      3%, 120  degrees C, 15 min), saccharified by commercial enzymes Novozymes(r)
      (Cellic CTec2 and HTec2). The influences of the pretreatments on the degradation
      of the lignin, cellulose and hemicellulose, porosity of the surface, particle
      crystallinity, and yield in reducing sugars after saccharification (Y RS), were
      established. Different concentrations of biomass (70 and 100 g/L in dry matter
      (dm)), with different physical differences (dry granulated, crushed wet bagasse,
      and whole pseudostem), were used. The broth with the highest Y RS among the
      different strategies tested was evaporated until the concentration of reducing
      sugars (RS) was to the order of 100 g/L and fermented, with and without prior
      detoxification with active carbon. Fermentation was carried out in Erlenmeyer
      flasks, at 30  degrees C, initial pH 5.0, and 120 rpm. In comparison to the
      biomass without chemical pretreatment and to the biomass pretreated with NaOH,
      the acid pretreatment of 70 g/L of dry granulated biomass enabled greater
      digestion of hemicellulose, lower index of cellulose crystallinity, and higher Y
      RS (45.8 +/- 0.7%). The RS increase in fermentation broth to 100 g/L, with
      posterior detoxification, presented higher productivity ethanol (Q P = 1.44 +/-
      0.02 g/L/h) with ethanol yield (Y P/RS) of 0.41 +/- 0.02 g/g. The value of Q P
      was to the order of 75% higher than Q P obtained with the same broth without
      prior detoxification.

PMID- 28455806
TI  - Ampicillin Mineralization by Denitrifying Process: Kinetic and Metabolic Effects.
AB  - The impact of the antibiotic ampicillin (AMP) on the metabolic and kinetics of
      denitrification process as well as the sludge ability for oxidizing it was
      evaluated in batch assays. Denitrifying reference assays with acetate-C and
      nitrate-N (C/N ratio of 1.1) were conducted for establishing the metabolic and
      kinetic performance of the denitrifying sludge. Assays amended with 10 mg AMP-C L
      1 were also performed. In reference assays, acetate and nitrate consumption
      efficiencies of 100% with a total conversion to HCO3- and N2 were achieved within
      1.5 h. When 10 mg AMP-C L-1 was added, total and simultaneous consumption of
      nitrate-N, acetate-C, and AMP-C was achieved within 12 h. The substrates were
      completely reduced to N2 and oxidized to HCO3-, respectively. No nitrite-N was
      registered at the end of culture. AMP caused a reversible inhibitory effect on
      specific nitrate and acetate consumption and N2 production rates. Complete
      consumption and mineralization of AMP associated to nitrate reduction to N2 were
      achieved. This work provides the first evidences on the metabolic and kinetic
      performance of a denitrifying sludge exposed to AMP. These results might be
      considered for proposing useful wastewater treatments where beta-Lactam
      antibiotics can be present.

PMID- 28455807
TI  - Bioethanol Production Using Waste Seaweed Obtained from Gwangalli Beach, Busan,
      Korea by Co-culture of Yeasts with Adaptive Evolution.
AB  - Conditions for ethanol production were evaluated using waste seaweed obtained
      from Gwangalli beach, Busan, Korea, after strong winds on January 15, 2015.
      Eleven types of seaweed were identified, and the proportions of red, brown, and
      green seaweed wastes were 26, 46, and 28%, respectively. Optimal pretreatment
      conditions were determined as 8% slurry content, 286 mM H2SO4 for 90 min at 121 
      degrees C. Enzymatic saccharification with 16 units/mL Celluclast 1.5L and
      Viscozyme L mixture at 45  degrees C for 48 h was carried out as optimal
      condition. A maximum monosaccharide concentration of 30.2 g/L was obtained and
      used to produce ethanol. Fermentation was performed with single or mixed yeasts
      of non-adapted and adapted Saccharomyces cerevisiae KCTC 1126 and Pichia
      angophorae KCTC 17574 to galactose and mannitol, respectively. The maximum
      ethanol concentration and yield of 13.5 g/L and YEtOH of 0.45 were obtained using
      co-culture of adapted S. cerevisiae and P. angophorae.

PMID- 28455808
TI  - Model-Based Nutrient Feeding Strategies for the Increased Production of
      Polyhydroxybutyrate (PHB) by Alcaligenes latus.
AB  - Polyhydroxyalkanoates (PHAs) are biodegradable polymers which are considered as
      an effective alternative for conventional plastics due to their mechanical
      properties similar to the latter. However, the widespread use of these polymers
      is still hampered due to their higher cost of production as compared to plastics.
      The production cost could be overcome by obtaining high yields and productivity.
      The goal of the present research was to enhance the yield of polyhydroxybutyrate
      (PHB) with the help of two simple fed-batch cultivation strategies. In the
      present study, average batch kinetic and substrate limitation/inhibition study
      data of Alcaligenes latus was used for the development of PHB model which was
      then adopted for designing various off-line nutrient feeding strategies to
      enhance PHB accumulation. The predictive ability of the model was validated by
      experimental implementation of two fed-batch strategies. One such dynamic
      strategy of fed-batch cultivation under pseudo-steady state with respect to
      nitrogen and simultaneous carbon feeding strategy resulted in significantly high
      biomass and PHB concentration of 39.17 g/L and 29.64 g/L, respectively. This
      feeding strategy demonstrated a high PHB productivity and PHB content of 0.6 g/L
      h and 75%, respectively, which were remarkably high in comparison to batch
      cultivation. The mathematical model can also be employed for designing various
      other nutrient feeding strategies.

PMID- 28455809
TI  - Renal Denervation Therapy for Drug-Resistant Hypertension: Does It Still Work?
AB  - OPINION STATEMENT: Hypertension is a global public health problem affecting one
      fourth of the world's population. A subset of these patients with resistant
      hypertension presents a particular management problem and suffers a marked
      increase in cardiovascular risk. Treatment options have been limited, but the
      past decade has witnessed the emergence of catheter-based renal denervation to
      interrupt the sympathetic nervous system, long considered to play an important
      role in the development and maintenance of hypertension. Phase 1 and 2 studies
      reported remarkable reductions in blood pressure and sparked an excessive
      exuberance that ground to a halt with negative results of the SYMPLICITY HTN-3
      pivotal trial. The subsequent and sober reappraisal has shed light on potential
      failure modes. Armed with appropriately cautious optimism, the field has resumed
      its move forward to realize the potential for therapeutic application in
      hypertension and other conditions characterized by sympathetic overactivity. This
      article summarizes the rich experimental data, early surgical experience, and
      available clinical trial results for catheter platforms. It concludes with
      discussion of knowledge gaps, lessons learned, and future directions.

PMID- 28455810
TI  - The Role of Religiousness/Spirituality and Social Networks in Predicting
      Depressive Symptoms among Older Korean Americans.
AB  - This study (1) examined the effects of religiousness/spirituality and social
      networks as predictors of depressive symptoms in older Korean Americans and (2)
      compared the best predictors of depressive symptoms. A cross-sectional survey was
      conducted with 200 older Korean Americans residing in the New York City area in
      2009. Best-subsets regression analyses were used to evaluate the best predictors
      of depressive symptoms. Nearly 30% of older Korean participants reported mild or
      severe depressive symptoms. The best model fit for depressive symptoms involved
      four predictors: physical health status, religious/spiritual coping skills,
      social networks, and annual household income. Social networks and
      religious/spiritual coping skills contributed significantly to the variance of
      depressive symptoms. Adding additional variables to the model did not enhance
      predictive and descriptive power. Religiousness/spirituality and social networks
      are important for coping with life stress and may be useful in developing
      effective health care strategies in the management of depression among older
      Korean Americans. Health education and intervention could be framed in ways that
      strengthen such coping resources for this population. Future research is needed
      to best guide prevention and intervention strategies.

PMID- 28455811
TI  - Historical Trends of Polycyclic Aromatic Hydrocarbons in the Reservoir Sediment
      of the Dianchi Watershed, Southwest China.
AB  - Using gas-chromatography/mass spectrometry (GC-MS) method dating data (210Pb and
      137Cs) and OCPs signatures, the temporal distribution of polycyclic aromatic
      hydrocarbons (PAHs) was investigated in dated sediment core from Baoxianghe
      reservoir in Dianchi watershed, Southwest China. The concentrations of total PAHs
      were in the range of 162.3-762.2 ng g-1 from 1945 to 2013. There showed an
      obvious increase from 1960s to 2000s. The distributions of PAHs were influenced
      by local population and Gross Domestic Product (GDP) during the period
      between1962 and 2004. PAHs sources changed from biomass or domestic coal
      combustion (before 1980) to liquid fossil fuel combustion (after 1980). Total
      toxic toxicity equivalents (TEQs) of the carcinogenic PAHs were very low (3.03
      28.08 ng g-1).

PMID- 28455812
TI  - Treatment Patterns among Children and Adolescents with Attention
      Deficit/Hyperactivity Disorder with or without Psychiatric or Neurologic
      Comorbidities in Sweden: A Retrospective Cohort Study.
AB  - INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a common
      psychiatric disorder in children/adolescents and occurs frequently with
      psychiatric/neurologic comorbidities. The objective of this study was to assess
      the impact of psychiatric/neurologic comorbidities on pharmacotherapy patterns
      among patients with ADHD in Sweden. METHODS: A retrospective cohort analysis was
      conducted using medical records from a regional database in Sweden. Patients aged
      6-17 years, with >=1 prescription for ADHD medication between July 1, 2007 and
      June 30, 2009, and continuously active in the database for >=12 months before and
      after their prescription index date were selected. Patients were categorized as
      ADHD alone (ADHD-only) or with comorbidities (ADHD-comorbid). Between-group
      differences were analyzed before and after adjusting for potentially confounding
      variables. RESULTS: Data on 1794 patients (1083 ADHD-only; 711 ADHD-comorbid)
      were analyzed. Among newly treated patients, 21.7% augmented their index therapy
      (ADHD-only, 20.5%; ADHD-comorbid, 24.4%; p = 0.23). After adjustment, ADHD-only
      patients were less likely (p = 0.002) to augment versus ADHD-comorbid patients
      [odds ratio = 0.44, 95% confidence interval (CI) 0.27, 0.73]. ADHD-comorbid
      patients received more prescriptions versus ADHD-only patients (mean 13.1 vs
      10.0; p < 0.001), and had more outpatient visits (mean 11.9 vs. 8.1; p < 0.001)
      and hospitalizations (10.7% vs. 6.0%; p < 0.001). After adjustment, ADHD-only
      patients had fewer outpatient visits (p < 0.001) and referrals (p < 0.001) versus
      ADHD-comorbid patients (visits: beta = -0.21, 95% CI -0.28, -0.13; referrals:
      beta = -0.25, 95% CI -0.33, -0.18). CONCLUSION: Patients with ADHD with
      comorbidities had more hospitalizations, physician visits, and medication
      prescriptions during 12 months' follow-up than did those with ADHD alone. ADHD
      therapy augmentation was prevalent among children/adolescents with ADHD, even
      among those without psychiatric/neurologic comorbidities.

PMID- 28455813
TI  - Prostaglandin actions in established insect cell lines.
AB  - Prostaglandins (PGs) are oxygenated metabolites of arachidonic acid (AA) and two
      other C20 polyunsaturated fatty acids that serve as biochemical signals mediating
      physiological functions. We reported that PGs influence protein expression in
      insect cell lines, which prompted the question: do PGs influence cell
      proliferation or viability in insect cell lines? Here, we report on the outcomes
      of experiments designed to address the question in cell lines from three insect
      orders: Hemiptera (squash bug, Anasa tristis, BCIRL-AtE-CLG15A), Coleoptera (red
      flour beetle, Tribolium castaneum, BCIRL-TcA-CLG1), and Lepidoptera (tobacco
      budworm, Heliothis virescens, BCIRL-HvAM1). Treating the insect cell lines with
      PGA1, PGA2, or PGD2 led to dose-dependent reductions in cell numbers. All three
      cell lines were sensitive to PGA1 and PGA2 (IC50s = 9.9 to 26.9 MUM) and were
      less sensitive to PGD2 (IC50s = 31.6 to 104.7 MUM). PG treatments also led to
      cell death at higher concentrations, as seen in mammalian cell lines. PGE1, PGE2,
      and PGF2alpha treatments did not influence AtE-CLG15A or HvAM1 cell numbers at
      lower concentrations, but led to dose-related reductions in TcA-CLG1 cells at
      higher concentrations. Similar treatments with pharmaceutical inhibitors of PG
      biosynthesis also led to reduced cell numbers: MAFP (inhibits phospholipase A2),
      indomethacin (inhibits PG biosynthesis), and esculetin (inhibits lipoxygenase).
      Because these pharmaceuticals are used to relieve inflammation and other medical
      issues in human medicine, they are not toxic to animal cells. We infer PGs are
      necessary in optimal quantities for ongoing homeostatic functions in established
      cell lines; in quantities outside the optimal concentrations, PGs are
      deleterious.

PMID- 28455814
TI  - Adaptations in corticospinal excitability and inhibition are not spatially
      confined to the agonist muscle following strength training.
AB  - PURPOSE: We used transcranial magnetic stimulation (TMS) to determine the
      corticospinal responses from an agonist and synergist muscle following strength
      training of the right elbow flexors. METHODS: Motor-evoked potentials were
      recorded from the biceps brachii and flexor carpi radialis during a submaximal
      contraction from 20 individuals (10 women, 10 men, aged 18-35 years; training
      group; n = 10 and control group; n = 10) before and after 3 weeks of strength
      training at 80% of 1-repetition maximum (1-RM). To characterise the input-output
      properties of the corticospinal tract, stimulus-response curves for corticospinal
      excitability and inhibition of the right biceps brachii and flexor carpi radialis
      were constructed and assessed by examining the area under the recruitment curve
      (AURC). RESULTS: Strength training resulted in a 29% (P < 0.001) increase in 1-RM
      biceps brachii strength and this was accompanied by a 19% increase in isometric
      strength of the wrist flexors (P = 0.001). TMS revealed an increase in
      corticospinal excitability AURC and a decrease in silent period duration AURC for
      the biceps brachii and flexor carpi radialis following strength training (all P <
      0.05). However, the changes in corticospinal function were not associated with
      increased muscle strength. CONCLUSION: These findings show that the corticospinal
      responses to strength training of a proximal upper limb muscle are not spatially
      restricted, but rather, results in a change in connectivity, among an agonist and
      a synergistic muscle relevant to force production.

PMID- 28455815
TI  - Perfusion Abnormalities are Frequently Detected by Early CT Perfusion and Predict
      Unfavourable Outcome Following Severe Traumatic Brain Injury.
AB  - BACKGROUND: In patients with severe traumatic brain injury (TBI), early CT
      perfusion (CTP) provides additional information beyond the non-contrast CT (NCCT)
      and may alter clinical management. We hypothesized that this information may
      prognosticate functional outcome. METHODS: Five-year prospective observational
      study was performed in a level-1 trauma centre on consecutive severe TBI
      patients. CTP (obtained in conjunction with first routine NCCT) was interpreted
      as: abnormal, area of altered perfusion more extensive than on NCCT, and the
      presence of ischaemia. Six months Glasgow Outcome Scale-Extended of four or less
      was considered an unfavourable outcome. Logistic regression analysis of CTP
      findings and core variables [preintubation Glasgow Coma Scale (GCS), Rotterdam
      score, base deficit, age] was conducted using Bayesian model averaging to
      identify the best predicting model for unfavourable outcome. RESULTS: Fifty
      patients were investigated with CTP (one excluded for the absence of TBI) [male:
      80%, median age: 35 (23-55), prehospital intubation: 7 (14.2%); median GCS: 5 (3
      7); median injury severity score: 29 (20-36); median head and neck abbreviated
      injury scale: 4 (4-5); median days in ICU: 10 (5-15)]. Thirty (50.8%) patients
      had an unfavourable outcome. GCS was a moderate predictor of unfavourable outcome
      (AUC = 0.74), while CTP variables showed greater predictive ability (AUC for
      abnormal CTP = 0.92; AUC for area of altered perfusion more extensive than NCCT =
      0.83; AUC for the presence of ischaemia = 0.81). CONCLUSION: Following severe
      TBI, CTP performed at the time of the first follow-up NCCT, is a non-invasive and
      extremely valuable tool for early outcome prediction. The potential impact on
      management and its cost effectiveness deserves to be evaluated in large-scale
      studies. LEVEL OF EVIDENCE III: Prospective study.

PMID- 28455816
TI  - A case of sarcoidosis with isolated hepatosplenic onset and development of
      inflammatory bowel disease during recovery stage.
AB  - Sarcoidosis is a systemic disease characterized by an immune-mediated disorder,
      which leads to the development of non-caseating granulomas in the involved
      organs. More than 90% of patients with sarcoidosis present lungs and lymphatic
      system involvement at onset, while less than 10% has an isolated extrapulmonary
      localization. Here, we describe the case of an elderly patient with isolated
      hepato-splenic onset (multiple splenic lesions at imaging and cholestasis), and
      subsequent pulmonary involvement. The liver biopsy showed the presence of non
      caseating granulomas, suggesting sarcoidosis. Despite the complete recovery was
      obtained with steroid therapy, after dosage reduction the patient presented
      watery diarrhea. Endoscopic investigations with biopsies were performed,
      describing the presence of an important lympho-plasmacytic infiltrate of terminal
      ileum mucosa with typical aspects of inflammatory bowel disease. The
      symptomatology completely disappeared after steroid dosage increase. This case
      confirms that sarcoidosis could present in a very atypical way, involving several
      organs in a different manner at the same time and that every symptom should not
      be underestimated, despite the rare presentation.

PMID- 28455818
TI  - Analysis of fatty acids in mouse tissue via in situ transmethylation with
      biochar.
AB  - Lipid derivatization technology-mediated fatty acid profiling studies have been
      suggested to dissect the contents of lipids in white fat and brown fat tissue.
      The focus of this study is to profile fatty acid lipidomics in brown adipose
      tissue and white adipose tissue of mice by derivatizing their lipids into fatty
      acid methyl esters via in situ transmethylation using a rice husk-derived biochar
      as porous media. The in situ transmethylation using biochar is advantageous in
      biological analysis because there was no loss of samples inevitably occurring in
      the loss of lipid in solvent extraction and purification steps.

PMID- 28455817
TI  - Induction of IL-10 cytokine and the suppression of T cell proliferation by
      specific peptides from red cell band 3 and in vivo effects of these peptides on
      autoimmune hemolytic anemia in NZB mice.
AB  - PURPOSE: The anion channel protein band 3 is the main target of the pathogenic
      red blood cells (RBC) autoantibodies in New Zealand black (NZB) mice. CD4 T cells
      from NZB mice with autoimmune hemolytic anemia respond to band 3. Previously, we
      have shown that IL-10 and peptides containing a dominant T cell epitope from red
      cell band 3 modulate autoimmune hemolytic anemia in NZB mice. Because of the
      immunoregulatory role of IL-10 in autoimmune diseases, we aim to identify
      individual band 3 peptides that induce high IL-10 production and simultaneously
      suppress CD4 T cell proliferation and to investigate the effect intranasal
      administration of IL-10 producing band 3 peptides on autoantibody responses of
      NZB mice. METHODS: Splenic CD4 T cells of NZB mice were isolated and stimulated
      by co-culture of T cells with individual band 3 peptides. IL-10 production was
      measured by enzyme-linked immunosorbent assay and proliferative response of CD4 T
      cells was estimated by incorporation of [3H] thymidine assay. NZB mice were given
      either PBS, or peptides 25 (241-251) and 29 (282-296) or both peptides
      intranasally on three occasions at 2-day intervals. The mice were bled at 6, 10
      and 18 weeks after peptide inhalation, and the number of RBC auto-antibodies was
      measured by DELAT and hematocrit values were assessed. RESULTS: Peptides 25 (241
      251) and 29 (282-296) induced the highest IL-10 production by CD4 T cells. These
      peptides also inhibited the peak T cell proliferative response. 6 and 10 weeks
      after peptide inhalation, the total IgG, IgG1 and IgG2a in mice treated with both
      peptides 241-251 and 282-296 were significantly higher than control (P < 0.05).
      However, no significant difference in the mean hematocrit between of the peptide
      treated mice and the control group was found. CONCLUSIONS: Although band 3
      peptides 241-251 and 282-296 induced to the highest IL-10 production by CD4 T
      cells in vitro but fail to reverse the RBC autoantibody response in vivo.
      Modifications to improve solubility these peptides might help to modulate the
      immune response toward a T helper-2 profile and decrease the severity of anemia.

PMID- 28455819
TI  - Preparation of nitrogen-doped Cu-biochar and its application into catalytic
      reduction of p-nitrophenol.
AB  - Nitrogen-doped copper-biochar (N-Cu-biochar) was synthesized via pyrolysis of
      glucose in the presence of copper and melamine and used as a catalyst in the
      reduction of p-nitrophenol by NaBH4. N-Cu-biochar was characterized by field
      emission scanning electron microscopy/energy-dispersive spectroscopy, Raman
      spectroscopy, X-ray Diffraction, and Brunauer-Emmett-Teller surface analyzer. The
      catalytic performance of N-Cu-biochar was evaluated under varying conditions of
      NaBH4 concentration, biochar dosage, and initial p-nitrophenol concentration. N
      Cu-biochar was composed of ~83% C, ~9% O, and ~8% Cu, with Cu/Cu2O phases evenly
      dispersed on graphitic carbon aggregates possessing both macro- and meso-pores. N
      Cu-biochar showed superior catalytic ability in mediating p-nitrophenol reduction
      as compared to Cu-biochar and N-doped biochar, achieving complete reduction of
      0.35 mM p-nitrophenol within 30 min at a dose of 0.25 g L-1. Reduction of p
      nitrophenol catalyzed by N-Cu-biochar followed pseudo-first-order kinetics, and
      the reaction rate was dependent upon NaBH4 concentration. The overall results
      indicate that biochar can be a suitable candidate as a support for catalyst
      synthesis, and N-doped Cu-biochar can be a promising catalyst for the reduction
      of p-nitrophenol.

PMID- 28455821
TI  - Erratum to: Rationale for the use of a fixed-dose combination in the management
      of hypertension: efficacy and tolerability of lercanidipine/enalapril.

PMID- 28455820
TI  - A review of source tracking techniques for fine sediment within a catchment.
AB  - Excessive transport of fine sediment, and its associated pollutants, can cause
      detrimental impacts in aquatic environments. It is therefore important to perform
      accurate sediment source apportionment to identify hot spots of soil erosion.
      Various tracers have been adopted, often in combination, to identify sediment
      source type and its spatial origin; these include fallout radionuclides,
      geochemical tracers, mineral magnetic properties and bulk and compound-specific
      stable isotopes. In this review, the applicability of these techniques to
      particular settings and their advantages and limitations are reviewed. By
      synthesizing existing approaches, that make use of multiple tracers in
      combination with measured changes of channel geomorphological attributes, an
      integrated analysis of tracer profiles in deposited sediments in lakes and
      reservoirs can be made. Through a multi-scale approach for fine sediment
      tracking, temporal changes in soil erosion and sediment load can be reconstructed
      and the consequences of changing catchment practices evaluated. We recommend that
      long-term, as well as short-term, monitoring of riverine fine sediment and
      corresponding surface and subsurface sources at nested sites within a catchment
      are essential. Such monitoring will inform the development and validation of
      models for predicting dynamics of fine sediment transport as a function of hydro
      climatic and geomorphological controls. We highlight that the need for monitoring
      is particularly important for hilly catchments with complex and changing land
      use. We recommend that research should be prioritized for sloping farmland
      dominated catchments.

PMID- 28455822
TI  - Erratum to: Subjective effects and safety of whole and tampered morphine sulfate
      and naltrexone hydrochloride (ALO-01) extended-release capsules versus morphine
      solution and placebo in experienced non-dependent opioid users: a randomized,
      doubleblind, placebo-controlled, crossover study.

PMID- 28455823
TI  - [Impact of conflicts of interest on guideline recommendations : Empirical study
      within the second update of the German interdisciplinary S3 guidelines on
      fibromyalgia syndrome].
AB  - BACKGROUND: The impact of conflicts of interest (COI) in general and of academic
      COI in particular on guideline recommendations in pain medicine has not yet been
      studied. Whether the inclusion of patients and of representatives of all relevant
      healthcare professions into a guidelines group is protective against a systematic
      bias of decisions of a guidelines group is currently unknown. METHODS: All
      members of the guidelines group declared their COI before the consensus
      conferences by a standard form according to the rules and standards of the
      Association of the German Medical and Scientific Societies. The acceptance or
      rejection and the strength of consensus of recommendations of the second update
      of the interdisciplinary guidelines on fibromyalgia syndrome was analyzed twice
      by first including and then excluding the votes of the guideline group members
      with COI related to a recommendation from the results of anonymous voting via an
      internet platform. RESULTS: A total of 42 persons from different healthcare
      professions and patients participated in the online voting on recommendations. Of
      the participants 29% had no COI according to the predefined criteria, 53% met the
      criteria of academic and 33% the criteria of financial COI. In the case of
      exclusion of participants with a COI related to a specific recommendation, 2 out
      of 23 recommendations (homeopathy, tramadol) were not accepted. In all votes,
      there were more participants without COI than with COI. CONCLUSION: Academic COI
      were more frequent than financial COI in the second update of the German
      interdisciplinary guidelines group on fibromyalgia syndrome. The impact of COI on
      guideline recommendations was low. The inclusion of patients and of all relevant
      healthcare professionals into a guidelines group is a protective factor against
      the influence of COI on guideline recommendations.

PMID- 28455824
TI  - Diallyl trisulfide ameliorates myocardial ischemia-reperfusion injury by reducing
      oxidative stress and endoplasmic reticulum stress-mediated apoptosis in type 1
      diabetic rats: role of SIRT1 activation.
AB  - Diallyl trisulfide (DATS) protects against apoptosis during myocardial ischemia
      reperfusion (MI/R) injury in diabetic state, although the underlying mechanisms
      remain poorly defined. Previously, we and others demonstrated that silent
      information regulator 1 (SIRT1) activation inhibited oxidative stress and
      endoplasmic reticulum (ER) stress during MI/R injury. We hypothesize that DATS
      reduces diabetic MI/R injury by activating SIRT1 signaling. Streptozotocin (STZ)
      induced type 1 diabetic rats were subjected to MI/R surgery with or without
      perioperative administration of DATS (40 mg/kg). We found that DATS treatment
      markedly improved left ventricular systolic pressure and the first derivative of
      left ventricular pressure, reduced myocardial infarct size as well as serum
      creatine kinase and lactate dehydrogenase activities. Furthermore, the myocardial
      apoptosis was also suppressed by DATS as evidenced by reduced apoptotic index and
      cleaved caspase-3 expression. However, these effects were abolished by EX527 (the
      inhibitor of SIRT1 signaling, 5 mg/kg). We further found that DATS effectively
      upregulated SIRT1 expression and its nuclear distribution. Additionally,
      PERK/eIF2alpha/ATF4/CHOP-mediated ER stress-induced apoptosis was suppressed by
      DATS treatment. Moreover, DATS significantly activated Nrf-2/HO-1 antioxidant
      signaling pathway, thus reducing Nox-2/4 expressions. However, the ameliorative
      effects of DATS on oxidative stress and ER stress-mediated myocardial apoptosis
      were inhibited by EX527 administration. Taken together, these data suggest that
      perioperative DATS treatment effectively ameliorates MI/R injury in type 1
      diabetic setting by enhancing cardiac SIRT1 signaling. SIRT1 activation not only
      upregulated Nrf-2/HO-1-mediated antioxidant signaling pathway but also suppressed
      PERK/eIF2alpha/ATF4/CHOP-mediated ER stress level, thus reducing myocardial
      apoptosis and eventually preserving cardiac function.

PMID- 28455825
TI  - Taxol alleviates collagen-induced arthritis in mice by inhibiting the formation
      of microvessels.
AB  - The objective of the present study is to evaluate the inhibitory effects of taxol
      (PTX) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. Collagen
      II (C II) and complete Freund's adjuvant (CFA) were used in C57BL/6 (H-2b) mice
      to generate the CIA model. Random grouping was performed in the normal control
      group, CIA model group, PTX 1.5 mg/kg group, PTX 1.0 mg/kg group, and PTX 0.5
      mg/kg group. Arthritis index scores, tissue pathology scores, and synovium
      microvessel density (MVD) analysis were performed. Immunohistochemistry and
      enzyme-linked immunosorbent assay were used to detect the expression of vascular
      endothelial growth factor (VEGF) and hypoxia-inducible factor-alpha (HIF-1alpha).
      The correlation between MVD and pathological scores and between MVD and the
      expression of VEGF as well as HIF-1alpha in the synovium were also evaluated.
      After PTX treatment, the three intervention group arthritis index scores were
      reduced when compared with the CIA group. The total histological scores in the
      three PTX treatment groups were lower than those in the CIA group. Similarly, PTX
      significantly alleviated the scores for synovitis, pannus formation, and bone
      destruction. Compared with the CIA group, the MVD of the three intervention
      groups decreased in a dose-dependent manner. The expression of VEGF and HIF
      1alpha in synovial tissues and serum also significantly decreased after PTX
      treatment. Further analysis showed that MVD and pathological scores and MVD and
      expression of VEGF as well as HIF-1alpha in the synovium were positively
      correlated. PTX may alleviate CIA by suppressing angiogenesis, providing new
      insights into the treatment of rheumatoid arthritis (RA). VEGF and HIF-1alpha may
      be targets for PTX suppression of microvessel formation.

PMID- 28455826
TI  - Subendocardial viability ratio in patients with rheumatoid arthritis: comparison
      with healthy controls and identification of prognostic factors.
AB  - Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability
      ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet
      it remains unclear whether it is affected in rheumatoid arthritis patients. We
      additionally sought predictors of SEVR in rheumatoid arthritis among a wide range
      of disease-related parameters, cardiac and hemodynamic factors, and markers of
      atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was
      estimated in rheumatoid arthritis patients and healthy controls by applanation
      tonometry, which was also used to evaluate arterial stiffness (pulse wave
      velocity and augmentation index). In the rheumatoid arthritis group, carotid
      intima-media thickness (cIMT) was additionally estimated by ultrasound, cardiac
      and hemodynamic parameters by impedance cardiography, and endothelial dysfunction
      by measurement of asymmetric dimethylarginine (ADMA). In a total of 122
      participants, SEVR was lower among 91 patients with rheumatoid arthritis compared
      to 31 controls (141.4 +/- 21.9 vs 153.1 +/- 18.7%, p = 0.009) and remained so
      among 29 rheumatoid arthritis patients without hypertension, diabetes, or
      cardiovascular diseases, compared to the control group (139.7 +/- 21.7 vs 153.1
      +/- 18.7%, p = 0.013). SEVR did not significantly correlate with arterial
      stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis
      revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025),
      cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular
      ejection time (p = 0.004) as independent predictors of SEVR among patients with
      rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of
      SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather
      than functional indices of endothelial and macrovascular dysfunction, may be
      useful as predictors of myocardial perfusion in rheumatoid arthritis.

PMID- 28455827
TI  - Characteristics and risk factors of lymphoproliferative disorders among patients
      with rheumatoid arthritis concurrently treated with methotrexate: a nested case
      control study of the IORRA cohort.
AB  - The purpose of the study is to demonstrate the characteristics of
      lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA)
      and risk factors for LPD among RA patients concurrently treated with methotrexate
      (MTX). Among patients who participated in the Institute of Rheumatology,
      Rheumatoid Arthritis (IORRA) cohort study in October 2010, past existence of LPD
      from patient's report was confirmed through medical charts. Background factors,
      LPD pathological findings, and the clinical courses of LPD and RA after LPD were
      assessed. To analyze the risk of MTX-associated LPD among RA patients
      concurrently treated with MTX, a nested case-control study design was used to
      select control patients who had received MTX but did not develop LPD by matching
      calendar date, sex, and age (within 5 years) at a 1:10 ratio. Odds ratios (ORs)
      with 95% confidence intervals (95% CIs) for occurrence of LPD were analyzed by
      multivariate analysis. Forty-eight patients experienced LPD among 5757 patients,
      and 25 (52.1%) of those had lymphoma. LPD regressed in 60.4% of all LPD patients
      and 24.0% of lymphoma patients. In the 26 cases who developed LPD during MTX
      treatment, multivariate analysis revealed that 28-joint disease activity score
      (DAS28) (OR 1.57 [95% CI, 1.12-1.57]; p < 0.01) and lactate dehydrogenase (LDH)
      level (OR 1.01 [95% CI, 1.00-1.02]; p < 0.01), but not concomitant dose of MTX,
      were risk factors for LPD. Among RA patients concomitantly treated with MTX, high
      disease activity, but not MTX dose, was a risk factor for the occurrence of LPD.

PMID- 28455828
TI  - Prevalence of hearing impairment in patients with rheumatoid arthritis,
      granulomatosis with polyangiitis (GPA, Wegener's granulomatosis), or systemic
      lupus erythematosus.
AB  - Hearing loss in patients with autoimmune diseases, such as systemic lupus
      erythematosus (SLE), granulomatosis with polyangiitis (GPA, Wegener's
      granulomatosis), or rheumatoid arthritis (RA), is controversial. Many studies
      lack measurements of bone-conduction thresholds to sufficiently differentiate
      between sensorineural hearing loss and conductive hearing loss. In addition, many
      studies lack control groups or comparisons to an age-related normal hearing
      threshold. This study investigates hearing performance with an extended
      audiological battery using psychoacoustic and objective measures. A total of 22
      adults with RA, 16 with GPA, 20 with SLE, and two age- and gender-matched control
      groups (n = 34 for GPA and RA and n = 42 for SLE) were included. Pure-tone
      hearing thresholds, speech perception in quiet and noise, tympanometry, and high
      resolution otoacoustic emissions were assessed. GPA patients exhibited impaired
      pure-tone hearing compared to the control group, whereas SLE and RA patients did
      not. In GPA patients, a larger air-bone gap indicated conductive hearing loss. In
      addition, speech perception was reduced exclusively in GPA patients. A
      significant correlation was found between hearing loss and both the cumulative
      steroid dose and number of organ manifestations in GPA and SLE patients. Our data
      indicate that GPA and SLE patients are at moderate-to-high risk of conductive
      hearing loss. In contrast, RA patients are at low risk of disease-associated
      hearing loss.

PMID- 28455829
TI  - A Novel Apremilast Nail Lacquer Formulation for the Treatment of Nail Psoriasis.
AB  - The objective was to prepare a novel nail lacquer formulation to improve the
      ungual and trans-ungual delivery of apremilast for the potential treatment of
      nail psoriasis. Nail lacquer formulation was prepared using Eudragit(r) S 100 as
      a film-forming polymer and the mixture of ethanol, ethyl acetate, and water as a
      solvent system. As a result of high-throughput screening studies, dexpanthenol
      and salicylic acid were found to be the potential penetration enhancers. After 7
      days of in vitro studies, the cumulative amount of apremilast delivered by the
      nail lacquer formulation across the nail plate was found to be ~3-fold (0.52 +/-
      0.07 MUg/cm2) more compared to control (nail lacquer formulation without
      enhancers) (0.19 +/- 0.02 MUg/cm2). The cumulative amount of apremilast retained
      in the nail plate in the case of nail lacquer formulation was 1.26 +/- 0.18
      MUg/mg which was found to be ~2-fold more compared to control (0.57 +/- 0.07
      MUg/mg). Human subject studies were performed on the nails of thumb and index
      finger of six volunteers for 15 days. As a result, the cumulative amount of
      apremilast retained in the free distal edge of the nail plate in the case of nail
      lacquer was found to be ~2-fold (0.93 +/- 0.14 MUg/mg) more related to control
      (0.41 +/- 0.04 MUg/mg). As a conclusion, nail lacquer formulation was found to be
      capable of delivering a substantial amount of apremilast into the nail apparatus;
      thus, it can be a potential option for the treatment of nail psoriasis.

PMID- 28455830
TI  - The "iatrogenic triad": polypharmacy, drug-drug interactions, and potentially
      inappropriate medications in older adults.
AB  - Background The elderly population is often in continuous use of several
      medications and is more subject to the "iatrogenic triad" of polypharmacy,
      potentially inappropriate medication use and drug-drug interactions. However, few
      studies have investigated these three factors concomitantly. Purpose To assess
      the prevalence and inter-relationship of potentially inappropriate medication
      (PIM) use, polypharmacy and drug-drug interactions in older adults, together with
      their associated factors. Setting city of Juiz de Fora, Brazil. Methods a cross
      sectional, observational and door-to-door epidemiologic study in community
      dwelling older adults was conducted. Main outcome measure The primary outcomes
      were polypharmacy, inappropriate medication use (2012 Beers and 2015 STOPP
      criteria) and drug-drug interactions. Associated factors were also investigated
      using bivariate and multivariate analyses. Results a total of 368 (92%) older
      adults were in continuous use of at least one drug. There was a high prevalence
      of polypharmacy (44.6%), drug-drug interaction (72.3%) and PIMs by Beers (42.1%)
      and PIMs by STOPP (46.2%). Analysis of the inter-relationship of the criteria
      (polypharmacy, PIMs STOPP and drug-drug interactions) revealed that 108 (29.3%)
      of the older adults had all three criteria concomitantly and multivariate
      analysis showed that frailty and having a caregiver were associated with this
      "iatrogenic triad". Conclusion A high prevalence of iatrogenic effects from drugs
      was found in the older adults assessed. One in every three elderly participants
      of the study had all three iatrogenic criteria concomitantly, highlighting the
      major public health impact of this problem. The results of this study can serve
      to inform new preventive and educational strategies for health professionals.

PMID- 28455831
TI  - Greater ability to express positive emotion is associated with lower projected
      cardiovascular disease risk.
AB  - Positive emotion is associated with lower cardiovascular disease (CVD) risk, yet
      some mechanisms remain unclear. One potential pathway is via emotional
      competencies/skills. The present study tests whether the ability to facially
      express positive emotion is associated with CVD risk scores, while controlling
      for potential confounds and testing for sex moderation. Eighty-two men and women
      underwent blood draws before completing self-report assessments and a performance
      test of expressive skill. Positive expressions were scored for degree of
      'happiness' using expression coding software. CVD risk scores were calculated
      using established algorithms based on biological, demographic, and behavioral
      risk factors. Linear regressions revealed a main effect for skill, with skill in
      expressing positive emotion associated with lower CVD risk scores. Analyses also
      revealed a sex-by-skill interaction whereby links between expressive skill and
      CVD risk scores were stronger among men. Objective tests of expressive skill have
      methodological advantages, appear to have links to physical health, and offer a
      novel avenue for research and intervention.

PMID- 28455832
TI  - Structure and Function of the Two-Component Cytotoxins of Staphylococcus aureus -
      Learnings for Designing Novel Therapeutics.
AB  - Staphylococcus aureus can produce up to five different bi-component cytotoxins:
      two gamma-hemolysins HlgAB and HlgCB, and leukocidins SF-PV (Panton Valentine
      leukocidin), ED (LukED) and GH (LukGH, also called LukAB). Their major function
      in S. aureus pathogenesis is to evade innate immunity by attacking phagocytic
      cells and to support bacterial growth by lysing red blood cells. The five
      cytotoxins display different levels of amino acid sequence conservation (30-82%),
      but all form a remarkably similar beta-barrel type pore structure (greatly
      resembling the mono-component toxin alpha-hemolysin) that inserts into the target
      cell membrane leading to necrotic cell death. This review provides an overview of
      the culmination of decades of research on the structure of these toxins, their
      unique sequence and structural features that helps to explain the observed
      functional differences, such as toxin potency towards different cell types and
      species, receptor specificity and formation of functional non-cognate toxin
      pairs. The vast knowledge accumulated in this field supports novel approaches and
      the design of therapeutics targeting these cytotoxins to tame virulence and fight
      S. aureus infections.

PMID- 28455833
TI  - Article on ketogenic dietary regimes for cancer highly misleading.

PMID- 28455834
TI  - Does the Public Prefer Health Gain for Cancer Patients? A Systematic Review of
      Public Views on Cancer and its Characteristics.
AB  - BACKGROUND: Policies such as the Cancer Drugs Fund in England assumed a societal
      preference to fund cancer care relative to other conditions, even if that
      resulted in lower health gain for the population overall. OBJECTIVE: The aim of
      this study was to investigate the evidence for such a preference among the UK
      public. METHODS: The MEDLINE, PubMed and Econlit electronic databases were
      searched for studies relating to preferences for prioritising cancer treatment,
      as well as studies relating to preferences for the characteristics of cancer
      (severity of disease, end-of-life). The searches were run in November 2015 and
      updated in March 2017. Empirical preference studies, studies of public views, and
      studies in English were included. RESULTS: We identified 24 studies relating to
      cancer preferences. Two directly addressed health trade-offs in the UK-one showed
      a preference for health gain in cancer, while the other found no such preference
      but provided results consistent with population health maximisation. Other
      studies mostly showed support for cancer but did not require a direct health
      trade-off. Severity and end-of-life searches identified 12 and 6 papers,
      respectively, which were additional to existing reviews. There is consistent
      evidence that people give priority to severe illness, while results for end-of
      life are mixed. CONCLUSION: We did not find consistent support for a preference
      for health gains to cancer patients in the context of health maximisation. The
      evidence base is small and the results are highly sensitive to study design.
      There remains a contradiction between these findings and the popular view of
      cancer, and further work is required to determine the features of cancer which
      contribute to that view.

PMID- 28455835
TI  - Surgical approaches in hereditary endocrine tumors.
AB  - Endocrine tumors of thyroid, adrenal and parathyroid glands may be due to
      germline and inheritable mutations in 5-30% of patients. Medullary Thyroid
      Carcinoma, Pheochromocytoma, Paraganglioma, and Familial Primary
      Hyperparathyroidism are the most frequent entity. Hereditary endocrine tumors
      usually have a suggestive familial history; they occur earlier than sporadic
      variants, are multifocal, and have increased recurrence rates. They may be
      present as isolated variant or associated to other neoplasms in a syndromic
      setting. Genetic diagnosis should be preferably available before surgery because
      specific and targeted operative management are needed to achieve the best chance
      of cure. This review was aimed to discuss the surgical approaches for some of the
      most frequent hereditary endocrine tumors of thyroid, adrenal and parathyroid
      glands, focusing on medullary thyroid carcinoma, Pheochromocytoma, Paraganglioma
      and hereditary primary hyperparathyroidism (pHPT). Hereditary Medullary Thyroid
      Carcinoma is caused by RET mutations, and may be associated to Pheochromocytomas
      in MEN 2 setting. Total thyroidectomy and at least central neck nodal dissection
      is required. The availability of genetic screening allows prophylactic or early
      surgery in asymptomatic patients, with subsequent definitive cure. Hereditary
      Pheochromocytomas may be present in several syndromes (MEN 2, VHL, NF1,
      Paraganglioma/Pheochromocytoma syndrome); it may involve both adrenals; in these
      cases, a cortical sparing adrenalectomy should be performed to avoid permanent
      hypocorticosurrenalism. Hereditary Primary Hyperparathyroidism may frequently
      occur associated to MEN 1, MEN 2A, MEN 4, Hyperparathyroidism-Jaw Tumor Syndrome;
      it may involve all the parathyroid glands, requiring subtotal parathyroidectomy
      or total parathyroidectomy plus autotransplantation. In some cases, a selective
      parathyroidectomy might be performed.

PMID- 28455836
TI  - Access to safe abortion in Uganda: Leveraging opportunities through the harm
      reduction model.
AB  - Access to safe and legal abortion services is a far reach for women and girls in
      Uganda. Although unsafe abortion rates have fallen from 54 to 39 per 1000 women
      aged 15-45 years over a decade, absolute figures show a rise from 294 000 in 2003
      to 314 000 women having unsafe abortions in 2013. Unfortunately, only 50% of the
      women who develop abortion complications are able to reach facilities for
      postabortion care. Despite the clinical evidence and the stories from
      undocumented cases, debate on access to safer and legal abortion is constricted,
      moralized, and stigmatized. The harm reduction model has shown evidence of
      benefit in reducing maternal mortality and morbidity due to unsafe abortion while
      addressing related stigma and discrimination and advancing women's reproductive
      health rights. This article presents a case for promoting the model in Uganda.

PMID- 28455837
TI  - Valve interstitial cell culture: Production of mature type I collagen and precise
      detection.
AB  - Collagen often acts as an extracellular and intracellular marker for in vitro
      experiments, and its quality defines tissue constructs. To validate collagen
      detection techniques, cardiac valve interstitial cells were isolated from pigs
      and cultured under two different conditions; with and without ascorbic acid. The
      culture with ascorbic acid reached higher cell growth and collagen deposition,
      although the expression levels of collagen gene stayed similar to the culture
      without ascorbic acid. The fluorescent microscopy was positive for collagen
      fibers in both the cultures. Visualization of only extracellular collagen
      returned a higher correlation coefficient when comparing the immunolabeling and
      second harmonic generation microscopy images in the culture with ascorbic acid.
      Lastly, it was proved that the hydroxyproline strongly contributes to the second
      order susceptibility tensor of collagen molecules, and therefore the second
      harmonic generation signal is impaired in the culture without ascorbic acid.

PMID- 28455842
TI  - Body frame size in school children is related to the amount of adipose tissue in
      different depots but not to adipose distribution.
AB  - OBJECTIVES: The main aim of this study was to test the hypothesis that body frame
      size is related to the amount of fat in different adipose tissue depots and to
      fat distribution in schoolchildren. METHODS: Children aged between 5 and 10 years
      were included in this cross-sectional study (n = 565). Body frame size, adiposity
      markers (anthropometric, skinfolds thickness, and ultrasound measures), and fat
      distribution indices were analyzed. Correlation coefficients adjusted by
      reliability were estimated and analyzed by sex; the significance of the
      difference between two correlation coefficients was assessed using the Fisher z
      transformation. RESULTS: The sample included primarily urban children; 58.6% were
      normal weight, 16.1% overweight, 19.6% obese, and the rest were underweight.
      Markers of subcutaneous adiposity, fat mass and fat-free mass, and preperitoneal
      adiposity showed higher and significant correlations with the sum of the
      biacromial + bitrochanteric diameter than with the elbow diameter, regardless of
      sex. The fat distribution conicity index presented significant but weak
      correlations; and visceral adipose tissue, hepatic steatosis, and the waist-for
      hip ratio were not significantly correlated with body frame size measures.
      CONCLUSIONS: Body frame size in school children was related to the amount of
      adipose tissue in different depots, but not adipose distribution. More studies
      are needed to confirm this relationship and its importance to predict changes in
      visceral fat deposition during growth.

PMID- 28455843
TI  - Does the intercept of the heat-stress relation provide an accurate estimate of
      cardiac activation heat?
AB  - KEY POINTS: The heat of activation of cardiac muscle reflects the metabolic cost
      of restoring ionic homeostasis following a contraction. The accuracy of its
      measurement depends critically on the abolition of crossbridge cycling. We
      abolished crossbridge activity in isolated rat ventricular trabeculae by use of
      blebbistatin, an agent that selectively inhibits myosin II ATPase. We found
      cardiac activation heat to be muscle length independent and to account for 15-20%
      of total heat production at body temperature. We conclude that it can be
      accurately estimated at minimal muscle length. ABSTRACT: Activation heat arises
      from two sources during the contraction of striated muscle. It reflects the
      metabolic expenditure associated with Ca2+ pumping by the sarcoplasmic reticular
      Ca2+ -ATPase and Ca2+ translocation by the Na+ /Ca2+ exchanger coupled to the Na+
      ,K+ -ATPase. In cardiac preparations, investigators are constrained in estimating
      its magnitude by reducing muscle length to the point where macroscopic twitch
      force vanishes. But this experimental protocol has been criticised since, at zero
      force, the observed heat may be contaminated by residual crossbridge cycling
      activity. To eliminate this concern, the putative thermal contribution from
      crossbridge cycling activity must be abolished, at least at minimal muscle
      length. We achieved this using blebbistatin, a selective inhibitor of myosin II
      ATPase. Using a microcalorimeter, we measured the force production and heat
      output, as functions of muscle length, of isolated rat trabeculae from both
      ventricles contracting isometrically at 5 Hz and at 37 degrees C. In the presence
      of blebbistatin (15 MUmol l-1 ), active force was zero but heat output remained
      constant, at all muscle lengths. Activation heat measured in the presence of
      blebbistatin was not different from that estimated from the intercept of the heat
      stress relation in its absence. We thus reached two conclusions. First,
      activation heat is independent of muscle length. Second, residual crossbridge
      heat is negligible at zero active force; hence, the intercept of the cardiac heat
      force relation provides an estimate of activation heat uncontaminated by
      crossbridge cycling. Both results resolve long-standing disputes in the
      literature.

PMID- 28455844
TI  - Open Probe fast GC-MS - combining ambient sampling ultra-fast separation and in
      vacuum ionization for real-time analysis.
AB  - An Open Probe inlet was combined with a low thermal mass ultra-fast gas
      chromatograph (GC), in-vacuum electron ionization ion source and a mass
      spectrometer (MS) of GC-MS for obtaining real-time analysis with separation. The
      Open Probe enables ambient sampling via sample vaporization in an oven that is
      open to room air, and the ultra-fast GC provides ~30-s separation, while if no
      separation is required, it can act as a transfer line with 2 to 3-s sample
      transfer time. Sample analysis is as simple as touching the sample, pushing the
      sample holder into the Open Probe oven and obtaining the results in 30 s. The
      Open Probe fast GC was mounted on a standard Agilent 7890 GC that was coupled
      with an Agilent 5977A MS. Open Probe fast GC-MS provides real-time analysis
      combined with GC separation and library identification, and it uses the low-cost
      MS of GC-MS. The operation of Open Probe fast GC-MS is demonstrated in the 30-s
      separation and 50-s full analysis cycle time of tetrahydrocannabinol and
      cannabinol in Cannabis flower, sub 1-min analysis of trace trinitrotoluene
      transferred from a finger onto a glass surface, vitamin E in canola oil, sterols
      in olive oil, polybrominated flame retardants in plastics, alprazolam in Xanax
      drug pill and free fatty acids and cholesterol in human blood. The extrapolated
      limit of detection for pyrene is <1 fg, but the concentration is too high and the
      software noise calculation is untrustworthy. The broad range of compounds
      amenable for analysis is demonstrated in the analysis of reserpine. The possible
      use with alternate standard GC-MS and Open Probe fast GC-MS is demonstrated in
      the analysis of heroin in its street drug powder. The use of Open Probe with the
      fast GC acting as a transfer line is demonstrated in <10-s analysis without
      separation of ibuprofen and estradiol. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28455845
TI  - Do traumatic events have more impact on the development of dental anxiety than
      negative, non-traumatic events?
AB  - The importance of exposure to traumatic events for the development of dental
      anxiety has not been investigated. The aim of the present study was to test the
      hypotheses that individuals who reported having been exposed to a traumatic event
      [that is, fulfilling Criterion A of the Diagnostic and Statistical Manual of
      Mental Disorders, 5th Edition (DSM-5), for post-traumatic stress disorder (PTSD)]
      as the cause of their dental anxiety would report significantly higher levels of
      dental anxiety, typical trauma-related (PTSD) symptoms, and greater disturbance
      of memories involving these events than those who reported being exposed to non
      traumatic events. Patients of a specialized dental fear clinic (n = 90) were
      divided into those who reported a traumatic event that initiated their dental
      trait anxiety and those who did not. The two groups did not differ in their
      severity of dental anxiety and number of PTSD symptoms, but the memories of those
      who had been exposed to traumatic events were significantly more vivid than the
      memories of those in the reference group. Length of time since the event took
      place did not play a role. Hence, traumatic events are remembered more vividly,
      but do not seem to initiate more severe forms of dental anxiety than other
      events.

PMID- 28455846
TI  - Tool use in neurodegenerative diseases: Planning or technical reasoning?
AB  - Recent works showed that tool use can be impaired in stroke patients because of
      either planning or technical reasoning deficits, but these two hypotheses have
      not yet been compared in the field of neurodegenerative diseases. The aim of this
      study was to address the relationships between real tool use, mechanical problem
      solving, and planning skills in patients with Alzheimer's disease (AD, n = 32),
      semantic dementia (SD, n = 16), and corticobasal syndrome (CBS, n = 9). Patients
      were asked to select and use ten common tools, to solve three mechanical
      problems, and to complete the Tower of London test. Motor function and episodic
      memory were controlled using the Purdue Pegboard Test and the BEC96
      questionnaire, respectively. A data-transformation method was applied to avoid
      ceiling effects, and single-case analysis was performed based on raw scores and
      completion time. All groups demonstrated either impaired or slowed tool use.
      Planning deficits were found only in the AD group. Mechanical problem-solving
      deficits were observed only in the AD and CBS groups. Performance in the Tower of
      London test was the best predictor of tool use skills in the AD group, suggesting
      these patients had general rather than mechanical problem-solving deficits.
      Episodic memory seemed to play little role in performance. Motor dysfunction
      tended to be associated with tool use skills in CBS patients, while tool use
      disorders are interpreted as a consequence of the semantic loss in SD in line
      with previous works. These findings may encourage caregivers to set up disease
      centred interventions.

PMID- 28455847
TI  - Assessment of sexual function in Japanese men with prostate cancer undergoing
      permanent brachytherapy without androgen deprivation therapy: Analysis from the
      Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation
      database.
AB  - OBJECTIVES: To evaluate male sexual function in Japanese prostate cancer patients
      undergoing permanent brachytherapy without endocrine treatment, using quality of
      life measures of the Expanded Prostate Cancer Index Composite. METHODS: A total
      of 482 patients were selected as analysis subjects from the nationwide database
      for the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed
      Implantation. The patients were asked to complete the Expanded Prostate Cancer
      Index Composite questionnaires before and at 3, 12, 24, and 36 months after the
      permanent brachytherapy. Changes in their responses were analyzed, and any
      association of the outcomes was investigated. Furthermore, changes over time in
      their answers to Q18 (usual quality of your erections) were analyzed. RESULTS: A
      total of 72 patients (14.9%) had received external beam radiation. A total of 68
      patients (14.1%) had taken any 5-phosphodiesterase inhibitor medications.
      Regarding Q18, 232 patients (48.2%) selected either "There was no sexual
      activity" or "There was no desire for erection" before receiving permanent
      brachytherapy. Of all the 482 patients, sexual function was preserved in 138
      patients (28.7%) 3 years after permanent brachytherapy. Overall satisfaction has
      significantly improved without regard for the deterioration of sexual function.
      Significant factors for maintaining sexual activity were patient age and sexual
      activity before permanent brachytherapy. CONCLUSIONS: In Japanese patients
      undergoing permanent brachytherapy alone for prostate cancer, the sexual function
      is not well preserved. However, decreased sexual function does not seem to
      represent a major factor determining patients' overall satisfaction. These
      findings might be peculiar to Japanese patients, in whom elderly subjects account
      for the majority.

PMID- 28455848
TI  - 1 H and 13 C NMR spectral assignments for 24 novel naphthalenylphenylpyrazolines.

PMID- 28455849
TI  - Coupling I-125 permanent implant prostate brachytherapy Monte Carlo dose
      calculations with radiobiological models.
AB  - PURPOSE: To investigate the coupling of radiobiological models with patient
      specific Monte Carlo (MC) dose calculations for permanent implant prostate
      brachytherapy (PIPB). To compare radiobiological indices evaluated with different
      radiobiological models using MC and simulated AAPM TG-43 dose calculations.
      METHODS: Three-dimensional dose distributions previously computed using MC
      techniques with two types of patient models, TG43sim (AAPM TG-43 water-based
      conditions) and MCDmm (realistic tissues and interseed effects), for 613 PIPB
      patients are coupled with biological dose and tumour control probability (TCP)
      models. Two approaches and their extensions are considered to evaluate biological
      doses, biologically effective dose (BED) and isoeffective dose (IED), as well as
      two methods to evaluate TCP. Three novel extensions of equivalent uniform
      biologically effective dose (EUBED) are suggested which consider the spatial
      distribution of doses within the target volume. Adopted radiobiological model
      parameter values (alpha, beta, etc) are those suggested by AAPM TG-137, and
      sensitivity to parameter choice is discussed. RESULTS: MCDmm dose calculations
      can reveal low doses in the prostate target volume, due to tissue heterogeneities
      or inter-seed effects; considering these low doses in EUBED calculations can
      lower TCP estimates by up to 70%, with largest differences in patients with
      calcifications. There are large variations in biological doses and TCPs evaluated
      over the 613 patient cohort for each radiobiological model considered, reflecting
      the spectrum of physical doses calculated for these patients with either MCDmm or
      TG43sim. Depending on the model details, BED, IED and EUBED are, on average, 6.0
      9.8%, 7.4-9.2% and 1.8-15% higher, respectively, with TG43sim than MCDmm. TCP
      estimates computed using MCDmm dose distributions are much lower than expected
      based on past treatment outcome studies, suggesting a need to re-assess model
      parameters when evaluating radiobiological indices coupled with heterogeneous
      tissue model-based dose calculations. CONCLUSIONS: Cohort average differences in
      biological dose and TCP estimates between radiobiological models are generally
      larger than differences for any one radiobiological model evaluated with TG43sim
      or MCDmm dose calculations. However, heterogeneous tissue dose calculations, like
      MCDmm, can identify clinically-relevant low dose volumes, e.g., in patients with
      calcifications, which would otherwise be missed with TG-43. In addition to
      affecting physical dose distributions, these low dose volumes can largely impact
      radiobiological dose and TCP estimates, which further motivates the clinical
      implementation of model-based dose calculations for PIPB.

PMID- 28455850
TI  - Major trauma in the older patient: Evolving trauma care beyond management of
      bumps and bruises.

PMID- 28455851
TI  - Fragmentation behavior of DOTA complexes under different activation conditions.
AB  - We have investigated the fragmentation behavior of a number of DOTA-metal
      complexes under collision-induced dissociation, infrared-multiphoton dissociation
      and higher-energy collisional dissociation activation conditions. Both, positive
      and negative ion mode electrospray ionization was applied. The results show that
      characteristic fragmentations were obtained for the metal-complexes under the
      investigated conditions. All elemental compositions of fragment ions have been
      unambiguously identified by high resolution-accurate mass measurements. Certain
      trends, for instance eliminations of carbon dioxide, alkyl and amine residues,
      were observed that coincide with the size of the metal and its location within
      the periodic table. Additionally, lanthanide, aluminium and indium species with
      even oxidation state or containing a radical have been detected. To further
      investigate the observed water capture during activation, deuterium labeling
      experiments have also been carried out. Copyright (c) 2017 John Wiley & Sons,
      Ltd.

PMID- 28455852
TI  - Practical application of in silico fragmentation based residue screening with ion
      mobility high-resolution mass spectrometry.
AB  - RATIONALE: A screening concept for residues in complex matrices based on liquid
      chromatography coupled to ion mobility high-resolution mass spectrometry LC/IMS
      HRMS is presented. The comprehensive four-dimensional data (chromatographic
      retention time, drift time, mass-to-charge and ion abundance) obtained in data
      independent acquisition (DIA) mode was used for data mining. An in silico
      fragmenter utilizing a molecular structure database was used for suspect
      screening, instead of targeted screening with reference substances. METHODS: The
      utilized data-independent acquisition mode relies on the MSE concept; where two
      constantly alternating HRMS scans (low and high fragmentation energy) are
      acquired. Peak deconvolution and drift time alignment of ions from the low
      (precursor ion) and high (product ion) energy scan result in relatively clean
      product ion spectra. A bond dissociation in silico fragmenter (MassFragment)
      supplied with mol files of compounds of interest was used to explain the observed
      product ions of each extracted candidate component (chromatographic peak).
      RESULTS: Two complex matrices (fish and bovine liver extract) were fortified with
      98 veterinary drugs. Out of 98 screened compounds 94 could be detected with the
      in silico based screening approach. The high correlation among drift time and m/z
      value of equally charged ions was utilized for an orthogonal filtration
      (ranking). Such an orthogonal ion mobility based filter removes multiply charged
      ions (e.g. peptides and proteins from the matrix) as well as noise and artefacts.
      Most significantly, this filtration dramatically reduces false positive findings
      but hardly increases false negative findings. CONCLUSIONS: The proposed screening
      approach may offer new possibilities for applications where reference compounds
      are hardly or not at all commercially available. Such areas may be the analysis
      of metabolites of drugs, pyrrolizidine alkaloids, marine toxins, derivatives of
      sildenafil or novel designer drugs (new psychoactive substances). Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 28455853
TI  - Exploring the optimal sequence of abiraterone and enzalutamide in patients with
      chemotherapy-naive castration-resistant prostate cancer: The Kyoto-Baltimore
      collaboration.
AB  - OBJECTIVES: To evaluate and compare the efficacy of sequential treatment with
      abiraterone followed by enzalutamide or vice versa for castration-resistant
      prostate cancer. METHODS: We retrospectively evaluated data on 198 consecutive
      chemotherapy-naive patients who had received both abiraterone and enzalutamide
      for castration-resistant prostate cancer at Kyoto University Hospital (including
      satellite hospitals) and at Johns Hopkins Cancer Center. Prostate-specific
      antigen progression-free survival and overall survival in patients treated with
      sequential abiraterone-to-enzalutamide versus enzalutamide-to-abiraterone without
      intervening therapies were compared. RESULTS: Overall, 113 patients were treated
      with the abiraterone-to-enzalutamide sequence and 85 with the enzalutamide-to
      abiraterone sequence. Median prostate-specific antigen progression-free survival
      was not significantly different between abiraterone and enzalutamide in the first
      line setting (hazard ratio 0.88, 95% confidence interval 0.66-1.19, P = 0.412),
      but there was an advantage favoring enzalutamide compared with abiraterone in the
      second-line setting (hazard ratio 0.67, 95% confidence interval 0.49-0.91, P =
      0.009). Furthermore, the combined prostate-specific antigen progression-free
      survival was significantly longer in the abiraterone-to-enzalutamide sequence
      than in the enzalutamide-to-abiraterone sequence (hazard ratio 0.56, 95%
      confidence interval 0.41-0.76, P < 0.001). The difference was significant even in
      multivariate analyses (hazard ratio 0.65, 95% confidence interval 0.42-0.99, P =
      0.044). There was no statistical difference in overall survival between the two
      sequences in univariate (hazard ratio 0.88, 95% confidence interval 0.53-1.43, P
      = 0.599) and multivariate analyses (hazard ratio 0.81, 95% confidence interval
      0.49-1.35, P = 0.427). CONCLUSIONS: The abiraterone-to-enzalutamide sequence
      might have more favorable efficacy in terms of combined prostate-specific antigen
      progression-free survival than the enzalutamide-to-abiraterone sequence, although
      no differences in overall survival were observed. This could possibly be
      attributable to longer prostate-specific antigen progression-free survival with
      second-line enzalutamide compared with abiraterone.

PMID- 28455855
TI  - Global ESRD Costs Associated with a Short Daily Hemodialysis Program in the
      United States.
AB  - In spite of the growing evidence that daily hemodialysis (DHD) improves clinical
      outcomes and quality of life, the additional dialysis costs are not currently
      reimbursed in the United States. Nor have there been reports of the effects of
      DHD on end-stage renal disease (ESRD) global costs, which would help predict the
      financial impact of DHD on the ESRD program. Since 1996, 22 patients (20 in
      center, 2 home) have switched from conventional thrice-weekly dialysis to short,
      daily dialysis with six treatments per week. Eighteen patients started for
      medical indications, and four started for nonmedical reasons. Causes of ESRD were
      the following: diabetes mellitus (6), hypertension (4), glomerulonephritis (6),
      hereditary (2), and other (4). Mean age was 56 +/- 16 years. Patients had an
      average of 3.3 major comorbidities. Weekly conventional HD dialysis times were
      divided into six DHD treatments, each 2.0 +/- 0.3 hours. Weekly Kt/V remained
      unchanged. Twenty-two patients were followed on DHD for 220 patient-months: 7
      patients died after 1.8 +/- 1.3 months, 2 were transplanted at 4.3 +/- 3.2
      months, and 2 discontinued DHD at 3.6 +/- 4.8 months. Eleven patients remain on
      DHD at 17.4 +/- 8.3 months. Actual costs per extra dialysis session are as
      follows: $14.30 for supplies and $3.20 for labor for setup/cleanup time (15
      minutes at $12.80/hour). Annualized DHD savings are based on comparison of doses
      of epoetin alpha (Epogen) and blood pressure medication at the start and after 12
      months of DHD. Hospitalization rates include all enrolled patients, comparing
      rates for the 12 months prior to DHD with the first year on DHD, or annualized
      rates for those on DHD less than one year. Cost assumptions are $9/ 1000 U
      Epogen, $1/blood pressure pill, and $1200/per day of hospitalization. Extra
      transportation costs were covered by the patients. No increased access problems
      were observed. For patients on short DHD longer than 12 months, supply and labor
      costs increased to $2733/patient/year; however, Epogen use was reduced 55%, and
      blood pressure medications were reduced 40%. For all patients who switched to
      DHD, hospitalization rates were reduced 24%. This resulted in a net savings of
      about $4241/patient/ year after 12 months on DHD. Overall ESRD costs were
      substantially decreased on DHD. These cost savings must be passed on to providers
      before DHD becomes more widely available.

PMID- 28455854
TI  - Establishing the True Structure of the Sorbicillinoid-Derived Isolate Rezishanone
      C by Total Synthesis.
AB  - The enantiomer, ent-4, of the true structure, 4, of the sorbicillinoid
      rezishanone C (sorbivinetone) has been synthesized from a homochiral cis-1,2
      dihydrocatechol that is itself generated through the whole-cell biotransformation
      of toluene. These studies together with dispersion-corrected DFT calculations
      support the proposal that rezishanone C is an artefact of the isolation process
      and arises through a Diels-Alder reaction between ethyl vinyl ether and
      sorbicillinol (3).

PMID- 28455856
TI  - Nightly Home Hemodialysis: Fifteen Months of Experience in Lynchburg, Virginia.
AB  - What constitutes adequate dialysis has been debated in the nephrology literature
      over the past eight years. The mortality rate of patients on dialysis in the
      United States is about 20% per year. We believed that short and infrequent
      dialysis sessions contributed to poor outcomes. To improve the results, Lynchburg
      Nephrology started the nightly home hemodialysis (NHHD) program in September
      1997. Ten patients were trained in the first 15 months of the program. Patients
      dialyzed 7 - 9 hours, 6 nights/week, using the Fresenius 2008H machine. A
      standard dialysis solution with 2.0 mEq/L potassium, calcium concentration of 3.0
      - 3.5 mEq/L was used. Dialysis solution flow rates were 200 - 300 mL/min. Serum
      phosphate levels were maintained above 2.5 mg/dL by adding 0 - 45 mL Fleet's
      Phosphosoda to the bicarbonate bath. Patients had marked improvement in quality
      of life as measured with the SF-36. Blood pressure was better controlled with
      fewer medications. All phosphate binders were eliminated. Caloric intake and
      protein intake increased to normal levels as measured by three-day dietary
      histories pre-NHHD, and at 3, 6, and 12 months on NHHD. Epoetin alfa dosages were
      reduced by about 50%. Nightly home hemodialysis should be considered as a
      valuable modality option for end-stage renal disease patients; it is potentially
      superior to conventional thrice-weekly hemodialysis.

PMID- 28455857
TI  - Blood Flow, Negative Pressure, and Hemolysis During Hemodialysis.
AB  - Blood flow, measured by an ultrasound flowmeter, and the extent of hemolysis were
      assessed during a single, routine dialysis in 100 patients. Before and after the
      hemodialysis session, blood was drawn for measurements of haptoglobin (HPT),
      hemoglobin (HGB), albumin (ALB), and lactate dehydrogenase (LDH). The average
      values were as follows: pump speed 510 mL/ min, real blood flow 422 mL/min,
      arterial chamber pressure -350 mm Hg, and venous chamber pressure 279 mm Hg.
      Haptoglobin concentrations were higher in patients with central vein catheters
      compared to patients with arteriovenous access. The meaning of this finding is
      unclear. Mean HPT concentrations increased significantly less during hemodialysis
      (2.37%) than concentrations of ALB (11.3%), HGB (9.17%), and LDH (18.2%),
      indicating that some hemolysis is present in all dialyses. In dialyses with
      arterial chamber pressures more negative than -350 the median concentration of
      ALB (8.70%) increased significantly more than the median concentration of HGB
      (7.99%). This indicates significantly more hemolysis in dialyses with more
      negative pressures compared to those with less negative arterial chamber
      pressures. Median LDH increased more in dialyses with more negative prepump
      chamber pressures (16.19% vs 13.78%), but not significantly; however, LDH
      increases were significantly higher than either HGB or ALB, thus indicating
      significantly more hemolysis in dialyses with more negative pressures compared to
      those with less negative arterial chamber pressures. Erythropoietin dose was not
      significantly different in patients dialyzed with more or less negative arterial
      chamber pressures (17 645 +/- 1226 U/week vs 16 308 +/- 1506 U/week). We conclude
      that dialyses with negative arterial chamber pressures greater than -350 mm Hg
      cause slightly higher hemolysis than dialyses with less negative arterial chamber
      pressures, but this increased hemolysis is not associated with an increased
      requirement of erythropoietin dose. Whether this increased hemolysis is of
      clinical significance is uncertain.

PMID- 28455858
TI  - Length of Dialysis Session Is More Important Than Large Kt/V in Hemodialysis.
AB  - Long, slow hemodialysis (3 * 8 hours/week) has been used without significant
      modification in Tassin, France, for 30 years with excellent morbidity and
      mortality rates. A long dialysis session easily provides high Kt/Vurea and allows
      for good control of nutrition and correction of anemia with a limited need for
      erythropoietin (EPO). Control of serum phosphate and potassium is usually
      achieved with low-dose medication. The good survival achieved by long
      hemodialysis sessions is essentially due to lower cardiovascular morbidity and
      mortality than in short dialysis sessions. This, in turn, is mainly explained by
      good blood pressure (BP) control without the need for antihypertensive
      medication. Normotension in this setting is due to the gentle but powerful
      ultrafiltration provided by the long sessions, associated with a low salt diet
      and moderate interdialytic weight gains. These allow for adequate control of
      extracellular volume (dry weight) in most patients without important
      intradialytic morbidity. Therefore, increasing the length of the dialysis session
      seems to be the best way of achieving satisfactory long-term clinical results.

PMID- 28455859
TI  - Laudatio: Professor Paul E. Teschan.

PMID- 28455860
TI  - Evolution of Daily Hemodialysis in Acute Renal Failure: From the Korean War to
      the Present.
AB  - Over half a century of hemodialysis therapy has brought significant progress in
      technology and in our approach to its use. This brief review has three
      objectives: (1) to describe what dialysis was like in the beginning, 50 years
      ago; (2) to review the origins and interval evolution of the paradigm of daily
      hemodialysis; and (3) to introduce some vistas for the future.

PMID- 28455861
TI  - Dialysis Therapy in the United States: A Historical Perspective.

PMID- 28455862
TI  - Effect of Low Dialysate Flow Rate on Hemodialyzer Mass Transfer Area Coefficients
      for Urea and Creatinine.
AB  - Recent work has shown that the dialyzer mass transfer area coefficient (Ko A) for
      urea increases when the dialysate flow rate is increased from 500 to 800 mL/min.
      In this study we determined urea and creatinine clearances for two commercial
      dialyzers containing polysulfone hollow fibers in vitro at 37 degrees C, a
      nominal blood flow rate of 300 mL/ min, and dialysate flow rates (Qd ) ranging
      from 100 to 800 mL/min. A standard bicarbonate dialysis solution was used in both
      the blood and dialysate flow pathways, and clearances were calculated from solute
      concentrations in the input and output flows on both the blood and dialysate
      sides. Urea and creatinine Ko A values, calculated from the mean of the blood and
      dialysate side clearances, increased (p < 0.01) with increasing Qd over the
      entire range studied. The increase in both urea and creatinine Ko A with
      increasing Qd was proportional to the Ko A value. These data show that changes in
      Qd alter small solute clearances greater than predicted assuming a constant Ko A.

PMID- 28455863
TI  - Daily Hemodialysis versus Standard Hemodialysis: TAC, TAD, Weekly eKt/V,
      std(Kt/V), and PCRn.
AB  - Seven patients, mean age 42.57 +/- 15.69 years (range 21 - 67 years), on standard
      hemodialysis (SHD), 4 - 5 hours, three times per week for 11.0 +/- 6.63 years
      (range 1 - 18 years), were switched to daily hemodialysis (DHD), 2 - 2.5 hours,
      six times per week. For each type of treatment similar parameters were applied,
      and the total weekly time was the same. Mean duration of DHD was 15.4 +/- 4.98
      months (range 7 - 20 months). We report here our results of quantification in
      each method, including time-averaged concentration (TAC), normalized protein
      catabolic rate (PCRn), equilibrated Kt/V (eKt/V), equivalent normalized
      continuous standard clearance [std(Kt/V)], equivalent renal urea clearance
      (eKRn), and time-averaged deviation (TAD). With DHD, urea TAC was reduced from
      19.09 +/- 3.47 to 15.16 +/- 3.21 mmol/L (p = 0.026), urea TAD diminished from
      4.76 +/- 1.04 to 2.52 +/- 0.57 mmol/L (p = 0.000 53), PCRn increased from 1.11 +/
      0.23 to 1.42 +/- 0.24 g/kg/day (p = 0.001), weekly eKt/V increased from 4.11 +/-
      0.31 to 4.74 +/- 0.43 (p = 0.000 25), std(Kt/V) rose from 2.17 +/- 0.06 to 4.02
      +/- 0.25 (p = 0.0001), and eKRn increased from 12.96 +/- 0.60 to 21.7 +/- 3.09
      mL/min (p = 0.000 45). On DHD the most important quantitative variation is the
      decrease of urea TAD (closer to that of a healthy kidney), due to the increased
      frequency of dialysis; std(Kt/V) practically doubled and represents 30% of that
      of normal renal function. These changes are probably the main explanation for the
      clinical improvements, but it is difficult to dissociate the effects of increased
      dialysis dose from the effects of decreased TAD.

PMID- 28455864
TI  - Prevention of Damage to Cuffed Catheters.
AB  - Cuffed catheters, although not ideal for long-term use, are now used more
      frequently due to an increase in the aging population, in whom the vessels are
      not suitable for either arteriovenous fistulas or polytetrafluoroethylene (PTFE)
      grafts. Infections and thrombosis remain the major causes for removal or change
      of catheters. We recently identified eight catheter defects that required
      replacement of catheters. Of these, two were due to patient negligence: one
      catheter was accidentally severed while the patient was shaving; the other was
      snipped during a haircut. One was believed to have a manufacturing defect. One
      catheter sustained needle-prick damage near the hub while irrigating the
      catheter. Two catheters were lost due to needle pricks during skin closure, and
      one catheter sustained similar damage while fixing the suture wing to the skin.
      The other two were damaged by suture material slicing through the lumen of the
      catheter as it expanded due to increased blood flow during repeated dialyses.
      Importantly, several of these injuries to the catheters were not immediately
      obvious and were detected only after repeated use of the catheters. Delayed
      bleeding of cuffed catheters necessitating change or removal has not been
      reported. Such bleeding may be due to manufacturing defects, patient
      carelessness, or iatrogenic causes. Avoiding the use of sutures can minimize the
      latter. Skin closure strips and a double transparent dressing may serve the same
      purposes, such as securing the catheter and aiding wound healing. In addition,
      these dressings have the added advantage of being waterproof, bacteria-proof, and
      cost effective.

PMID- 28455865
TI  - Modeling the Dose of Home Dialysis.
AB  - The growing interest in daily dialysis and combined continuous and intermittent
      dialysis treatments has created the need for a dialysis dosing model that is
      valid over a wide range of dosing frequency and intensity. Three models have been
      described for this purpose and are reviewed here. They have in common the concept
      of a continuous clearance value which is equivalent to the summed intermittent
      dialysis prescribed. The continuous clearance models all define a point on the
      saw-toothed blood urea nitrogen (BUN) concentration profile and calculate the
      continuous clearance required to achieve this at the same urea generation rate.
      The points modeled are the peak predialysis concentration (pkKt/V), the average
      Co (standard Kt/V, stdKt/V), and time-averaged urea concentration (TAC), which is
      termed equivalent renal clearance (EKRt/V). At the present time the only data for
      evaluation of clinical relevance of the three models is continuous ambulatory
      peritoneal dialysis (CAPD) outcome. The stdKt/V predicts that optimal CAPD
      outcome requires weekly stdKt/V 2.0, while the pkKt/V and EKRt/V models predict
      optimal doses of 1.8 and 3.0. These results suggest that the stdKt/V is the most
      realistic model, but data over much higher levels of therapy are not yet
      available to judge generalizability. The stdKt/V model was used to assess dose in
      two hemodialysis studies with 5 to 6 dialyses per week and showed that in one
      study the stdKt/V was only 2.0, while in the second study it was 5.6. These
      results show that dose can vary widely with a similar number of dialyses per week
      and point to the need for a generalized dosing model to guide and compare studies
      of daily home dialysis.

PMID- 28455866
TI  - Telematics Service for Home and Satellite Hemodialysis.
AB  - Home hemodialysis (HD) for the treatment of end-stage renal disease was first
      implemented about 30 years ago. In this paper the application of telematics
      monitoring services for supporting patients who need home HD or satellite HD is
      described. Two modified HD machines were located in two renal units, and a
      central control station (CCS, UNIX workstation with multimedia PC terminal) was
      located in another room of the hospital. Bidirectional communication between the
      modified HD machines and the CCS was managed using ISDN (Integrated Services
      Digital Network) links. Nine patients had 150 HD sessions performed using these
      HD machines over a period of 5 months. This system, called the HOMER-D system,
      provided on-line, remote supervision of the HD machine-related functions and the
      clinical condition of the patients through measurement of blood pressure, pulse
      rate, PO2 (pulse oxymetry), and ECG from the CCS. Any disturbances in the
      functioning of the HD machines were both visible and audible in the CCS, and the
      observer could give teleconsultation to the renal unit staff. No major dialysis
      associated complications were observed; all data and alarms were transmitted
      correctly; and patients received adequate HD treatment.

PMID- 28455867
TI  - Reflections on 24 Years of Renal Care.

PMID- 28455868
TI  - A Proposed Peritoneal-Based Wearable Artificial Kidney.
AB  - Ideally, an artificial kidney should simulate the normal kidney in providing
      continuous metabolic control, removal of toxins, and unrestricted patient
      freedom. Of the dialysis procedures available, continuous ambulatory peritoneal
      dialysis (CAPD) comes the closest to this ideal but provides inadequate dialysis
      and fails to remove protein-bound toxins. A continuous, wearable, peritoneal
      based artificial kidney is proposed in which the spent peritoneal dialysate is
      regenerated using a REDY sorbent cartridge one-tenth the size of the present
      cartridge, with the urease chemically bound to an inert support to eliminate the
      possibility of its displacement by protein in the spent dialysate. To simplify
      the flow path and to increase clearance, the dialysate flow will be through the
      peritoneal cavity using a dual lumen catheter instead of the traditional
      in/outflow through a single catheter. At a flow rate of 4 L/hour through the
      peritoneal cavity, of which 2 L/hour will pass through the sorbent cartridge, it
      is estimated that the weekly Kt/V will be 6.5 and the creatinine clearance will
      be 250 L. In addition, any protein in the spent peritoneal dialysate will be
      stripped of toxins by the sorbents and returned to the patient, thereby
      minimizing protein loss. The only disposables will be the sorbent cartridge and
      infusate, which will be changed every 8 hours.

PMID- 28455869
TI  - Time Needed to Improve Clinical Parameters By Daily Hemodialysis.
AB  - Daily hemodialysis therapy (DHD), 2 hours, 6 times per week, is able to cure
      complications that persist on standard hemodialysis (SHD), 4 hours, 3 times per
      week. Cardiovascular manifestations (high blood pressure, left ventricular
      hypertrophy), nutritional deficient states, and postdialysis asthenia are
      improved during the first month of DHD therapy and are usually cured at 3 months.
      Daily hemodialysis may be considered as a rescue therapy. The next step will be
      to select which patients can return to the classical SHD therapy without
      recurrence of their complications.

PMID- 28455870
TI  - Measurement of Hemodialysis Adequacy in a Changing World.
AB  - Defining adequacy of dialysis remains an elusive goal. The application of the
      Kt/Vurea concept to clinical dialysis was a major improvement in trying to define
      a dialysis dose. Intuitively, the Kt/V concept makes a great deal of sense: the
      urea clearance of the dialyzer during dialysis (K), multiplied by the time (t) of
      dialysis, divided by the patient's urea distribution volume (V) ought to give the
      best number to compare the efficiency of dialyses that patients receive. There
      are, however, many pitfalls associated with the whole Kt/Vurea concept.

PMID- 28455871
TI  - Nocturnal Home Hemodialysis: Patients' Personal Experiences.

PMID- 28455872
TI  - Blood Urea Nitrogen Stability: A Feasibility Study for Home Hemodialysis Adequacy
      Testing Through Mail.
AB  - Urea kinetic modeling measures the delivered dose of hemodialysis and is used to
      monitor dialysis adequacy. Obtaining samples for adequacy calculations is a
      challenge for home hemodialysis (HHD) patients. Ideally, the urea reduction ratio
      (URR) should be measured at a typical dialysis session; therefore, for HHD
      patients test specimens should be drawn at home and transferred to a clinical
      laboratory. Would blood urea nitrogen (BUN) remain stable if samples were mailed
      to the laboratory? To answer this question, BUN was measured in pre- and
      postdialysis samples from 20 patients over 8 days of laboratory storage. While
      BUN values varied among the patient population, neither pre- nor postdialysis
      values showed any significant variation during the 8-day storage time. These
      results suggest that BUN values are sufficiently stable for specimens to be drawn
      at home and mailed to a testing laboratory.

PMID- 28455873
TI  - Exogenous protease supplementation of poultry by-product meal-based diets for
      broilers: Effects on growth, carcass characteristics and nutrient digestibility.
AB  - An experiment was conducted to investigate the effects of three levels (0%, 3%
      and 6%) of poultry by-product meal (PBM) with or without protease on broiler
      growth, carcass characteristics and nutrient digestibility from 1 to 35 days. Two
      hundred and forty birds (n = 240) were fed equi-caloric and equi-nitrogenous (ME
      2850 kcal/kg; CP 20%) diets throughout the experiment. The enzyme supplementation
      increased feed intake (p < .01) and body weight gain (p < .01), but feed:gain
      remained unaffected (p > .05) from 1 to 21 days. Increasing level of PBM
      decreased feed intake (p < .05), but body weight gain was improved (p < .05) at
      3% PBM level during 1 to 21 days. The feed:gain was improved (p < .05) in birds
      fed diets containing 3% PBM. The feed:gain was also improved in birds fed diets
      containing 3% PBM from 1 to 35 days. However, feed intake and body weight gain in
      birds fed diets containing PBM remained unaffected. An interaction (p < .01) on
      feed intake between enzyme and PBM was noticed during 1 to 21 days. However, no
      interaction was recorded for body weight gain and feed:gain. The per cent carcass
      yield improved (p < .01) in birds fed diets supplemented with enzyme. The per
      cent breast meat yield was depressed (p < .005) in birds fed diets containing
      PBM. Apparent metabolizable energy (p < .001), nitrogen retention (p < .01),
      apparent metabolizable energy corrected for nitrogen (p < .001), and apparent
      digestibility coefficient for nitrogen (p < .01) improved in birds fed diets
      containing enzyme; however, a reverse was noticed in those fed diets containing
      only PBM. In conclusion, inclusion of 3% PBM along with supplementation of
      exogenous protease improved performance and nutrient digestibility in broilers.

PMID- 28455874
TI  - Quantitative identification of senescent cells in aging and disease.
AB  - Senescent cells are present in premalignant lesions and sites of tissue damage
      and accumulate in tissues with age. In vivo identification, quantification and
      characterization of senescent cells are challenging tasks that limit our
      understanding of the role of senescent cells in diseases and aging. Here, we
      present a new way to precisely quantify and identify senescent cells in tissues
      on a single-cell basis. The method combines a senescence-associated beta
      galactosidase assay with staining of molecular markers for cellular senescence
      and of cellular identity. By utilizing technology that combines flow cytometry
      with high-content image analysis, we were able to quantify senescent cells in
      tumors, fibrotic tissues, and tissues of aged mice. Our approach also yielded the
      finding that senescent cells in tissues of aged mice are larger than nonsenescent
      cells. Thus, this method provides a basis for quantitative assessment of
      senescent cells and it offers proof of principle for combination of different
      markers of senescence. It paves the way for screening of senescent cells for
      identification of new senescence biomarkers, genes that bypass senescence or
      senolytic compounds that eliminate senescent cells, thus enabling a deeper
      understanding of the senescent state in vivo.

PMID- 28455875
TI  - Effects of heavy metal pollution on pigmented macrophages in kidney of Vardar
      chub (Squalius vardarensis Karaman).
AB  - Pollution with heavy metals may influence the immune system of fish, leading to
      impairment of their health or even increase their mortality. The fish kidney is
      one of the first fish organs to be affected by water contamination. Amounts of
      kidney macrophages (MACs), which are involved in fish immune response, as well as
      the qualitative and quantitative changes in the pigmented MACs in fish kidney,
      are used as biomarkers of pollution. Therefore, in this study, we have evaluated
      relative and total volumes of trunk kidney pigmented MACs, and analyzed the
      pigments accumulated within them. Fish were sampled from two mining impacted
      rivers, Kriva and Zletovska, highly contaminated with heavy metals, and from one
      reference river, Bregalnica, in spring and autumn of 2012. We have observed that
      main pigments found in kidney MACs of Vardar chub were melanin and
      lipofuscin/ceroid, as well as that relative volumes of MACs ranged from 0.56 to
      1.68%. Moreover, the results showed that relative volumes of pigmented MACs were
      higher in metal contaminated rivers, especially in autumn season in the Zletovska
      River, concurrently with extremely high metal exposure. In addition, condition
      factors and kidney somatic indices were found significantly lower in the
      Zletovska River in both seasons, autumn and spring, possibly also as a
      consequence of high water pollution. Our data confirm that increase in relative
      volumes of pigmented MACs may serve as warning sign of potential heavy metal
      pollution in aquatic environment.

PMID- 28455876
TI  - Synthesis and Multi-Responsive Self-Assembly of Cationic Poly(caprolactone)
      Poly(ethylene glycol) Multiblock Copolymers.
AB  - Individual dissimilar blocks were combined to obtain well-defined An Bn and (A-B
      A)n types of cationic amphiphilic multiblock copolymers (MBCs) through mild
      sequential nucleophilic substitution without formation of byproducts. MBCs were
      synthesized by reacting end-functional polymer blocks of poly(caprolactone)
      (PCL), poly(ethylene glycol) (PEG), and PCL-b-PEG-b-PCL. For selective
      degradation, acid- and base-labile ester as well as reducible disulfide groups
      were introduced as linkers between the blocks. The micellar self-assemblies of
      these MBCs showed exceptional stability under normal physiological conditions
      with negligible release of the guest molecules. Selective disassembly under
      mildly acidic and basic conditions or in the presence of reducing agents caused
      triggered release of the guest molecules. This strategy is versatile and opens an
      opportunity to obtain a variety of tailor-made MBCs for selective and triggered
      release of therapeutics.

PMID- 28455878
TI  - Impact of plerixafor (mozobil) on hospital efficiency: A single center
      experience.
AB  - Plerixafor (Mozobil) in combination with granulocyte colony-stimulating factor (G
      CSF) has shown to increase mobilization of peripheral blood stem cells (PBSC) as
      compared to G-CSF alone in patients undergoing autologous stem cell
      transplantation (ASCT). However, up to 25% of patients treated with G-CSF alone
      still fail mobilization. Adding plerixafor to poor mobilizers allows to rescue
      these patients from mobilization failure and to reduce the number of apheresis
      sessions. The goal of this retrospective study was to capture the impact of
      plerixafor on treatment outcome and on apheresis department efficiency. The
      latter was measured in terms of time-slots lost, that is, the number of apheresis
      sessions scheduled but not carried out due to poor mobilization, and the number
      of elective apheresis sessions performed for patients undergoing extracorporeal
      photopheresis (ECP). Hospital records of patients treated before and after
      introduction of plerixafor were collected and analyzed. With plerixafor, the
      mobilization failure rate dropped from 12% to 4% and the mean number of time
      slots lost per patient dropped from 1.39 to 0.89. Additional drug costs due to
      plerixafor were partially balanced by a reduction in apheresis sessions,
      resulting in an additional cost of 759? per ASCT candidate. More importantly,
      with the use of plerixafor, the availability of time-slots turned from erratic to
      predictable such that freed capacity could be dedicated to other apheresis
      procedures. As a result, the number of ECP sessions increased from 0 in 2005 to
      685 sessions in 2014.

PMID- 28455877
TI  - Assessment of Left Atrial Deformation and Function by 2-Dimensional Speckle
      Tracking Echocardiography in Healthy Dogs and Dogs With Myxomatous Mitral Valve
      Disease.
AB  - BACKGROUND: The assessment of left atrial (LA) function by 2-dimensional speckle
      tracking echocardiography (STE) holds important clinical implications in human
      medicine. Few similar data are available in dogs. OBJECTIVES: To assess LA
      function by STE in dogs with and without myxomatous mitral valve disease (MMVD),
      analyzing LA areas, systolic function, and strain. ANIMALS: One hundred and fifty
      dogs were divided according to the American College of Veterinary Internal
      Medicine classification of heart failure: 23 dogs in class A, 52 in class B1, 36
      in class B2, and 39 in class C + D. METHODS: Prospective observational study.
      Conventional morphologic and Doppler variables, LA areas, and STE-based LA strain
      analysis were performed in all dogs and results were compared among groups.
      Correlation analysis was carried out between LA STE variables and other
      echocardiographic variables. RESULTS: Variability study showed good
      reproducibility for all the tested variables (coefficient of variation <16%).
      Left atrial areas, fractional area change, peak atrial longitudinal strain
      (PALS), peak atrial contraction strain, and contraction strain index (CSI)
      differed significantly between groups B2 and C + D and all the other groups
      (overall P < .001), whereas only PALS differed between groups B1 and A (P = .01).
      Left atrial areas increased with progression of the disease, whereas LA
      functional parameters decreased. Only CSI increased nonsignificantly from group A
      to group B1 and then progressively decreased. Thirty-one significant correlations
      (P < .001, r > .3) were found between conventional left heart echocardiographic
      variables and LA areas and strain variables. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Left atrial STE analysis provides useful information on atrial function in the
      dog, highlighting a progressive decline in atrial function with worsening of
      MMVD.

PMID- 28455879
TI  - Suprasternal Doppler as a haemodynamic tool in emergency care.

PMID- 28455880
TI  - NMR chemical shift and J coupling parameterization and quantum mechanical
      reference spectrum simulation for selected nerve agent degradation products in
      aqueous conditions.
AB  - The spectral parameters of selected nerve agent degradation products relevant to
      the Chemical Weapons Convention, namely, ethyl methylphosphonate, isopropyl
      methylphosphonate, pinacolyl methylphosphonate and methylphosphonic acid, were
      studied in wide range of pH conditions and selected temperatures. The pH and
      temperature dependence of chemical shifts and J couplings was parameterized using
      Henderson-Hasselbalch-based functions. The obtained parameters allowed
      calculation of precise chemical shifts and J coupling constants in arbitrary pH
      conditions and typical measurement temperatures, thus facilitating quantum
      mechanical simulation of reference spectra in the chosen magnetic field strength
      for chemical verification. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28455881
TI  - Mentoring in emergency medicine: The intersection of professional and personal
      development.

PMID- 28455882
TI  - Effect on Rendement Napole genotype on metabolic markers in Ossabaw pigs fed
      different levels of fat.
AB  - We investigated effects of Rendement Napole (RN) genotype on metabolic markers in
      Ossabaw pigs fed diets with different levels of dietary fat. Thirty-two pigs,
      belonging to either the wild-type (WT, rn+ /rn+ ) or carrier (CAR, RN- /rn+ )
      genotypes (n = 16/genotype), were divided into two dietary groups, (high fat [HF]
      or low fat [LF]) diets, for 12 weeks (n = 8 pigs/genotype/diet) after which pigs
      were killed for gene expression analysis by RT-PCR. Feeding HF diet caused
      increased daily gain (ADG, p < .05) and final body weight (BW) (p < .05) in
      comparison with the LF diet (p < .05). Feed efficiency (gain:feed) was higher (p
      < .05) in pigs on the HF and was higher (p < .05) in CAR pigs compared to WT.
      There was genotype * diet interaction (p = .05) on final BW such that CAR animals
      on LF diet had the same final BW as animals of both genotypes on HF diet. Carrier
      pigs on LF diet had higher (p < .05) average daily gain and gain:feed than WT
      pigs. There was a trend (p < .08) for a higher feed consumption in pigs on the LF
      diet. Backfat thickness was higher (p < .01) in pigs on the HF diet. Serum
      triglyceride was higher (0.62 vs. 0.33 mg/dl, p < .01) in pigs on HF diet. Serum
      insulin was higher (p < .05) in CAR versus WT pigs (0.40 vs. 0.015 MUg/ml). Pigs
      on the HF diet had a higher (p < .05) serum insulin compared to those on the LF
      diet (0.032 vs. 0.023 MUg/ml). Carnitine palmitoyl transferase 1-alpha was higher
      (p < .05) in the longissimus dorsi and semitendinosus muscles of pigs on HF diet.
      Acyl-CoA oxidase I was elevated (p < .05) in the liver of pigs on HF diet. Fatty
      acid synthase was lower in the longissimus dorsi muscle, liver and mesenteric fat
      (p < .05) of carrier pigs. The RN gene regulates specific metabolic markers in
      the Ossabaw pigs.

PMID- 28455883
TI  - Dietary pea fibre alters the microbial community and fermentation with increase
      in fibre degradation-associated bacterial groups in the colon of pigs.
AB  - This study was attempted to investigate the influence of dietary pea fibre (PF)
      on the community and quantity of colonic bacteria of piglets and finisher pigs
      using pyrosequencing data and real-time PCR. The concentration of acetate in
      colonic digesta from PF-fed piglets was significantly higher than that from
      control (p < .05). Feeding PF diet to finisher pigs increased the ratio of
      acetate to total volatile fatty acids (VFAs) but decreased the ratio of butyrate,
      as compared with the control pigs (p < .05 in both cases). The lower ratio of
      butyrate in samples from finisher pigs receiving PF suggested that this dietary
      fibre did not favour butyrate production in the hindgut. Supplementation of PF to
      piglets reduced abundance of Bacteroidetes, as compared with control animals.
      However, PF had opposite effects in finisher pigs, higher abundance of
      Bacteroidetes but lower of Firmicutes. Lactobacillus and Prevotella were found as
      the predominant genera in PF piglets. Prevotella accounted for nearly half of the
      total bacteria in the colon of finisher pigs in the PF group, but only one-third
      in the control animals. Quantitative PCR showed that Firmicutes/Bacteroidetes
      were significantly increased in the colon of PF piglets (p < .05) as compared
      with control animals, but decreased in PF finisher pigs. Bacteroidetes-Prevotella
      Porphyromonas and Desulfovibrio desulfuricans which are involved in degradation
      of dietary fibres were more abundant in the PF finisher pigs than in the controls
      (p < .05), suggesting mutualism between host and its gut microbes.

PMID- 28455884
TI  - Two Hour Evaluation and Referral Model for Shorter Turnaround Times in the
      emergency department.
AB  - OBJECTIVE: The objective of this study was to assess the implementation of a
      novel ED model of care, which combines clinical streaming, team-based assessment
      and early senior consultation to reduce length of stay. METHODS: A pre-post
      intervention study was used to compare ED performance following an extensive
      clinical redesign programme. Clinical teams and work sequences were reconfigured
      to promote the role of the staff specialist, with a focus on earlier decisions
      regarding disposition. Primary outcome measures were ED length of stay and
      National Emergency Access Target (NEAT) compliance. Secondary outcomes included
      referral and workup times, wait times by triage category, ambulance offload
      times, ward discharges and unit transfers within 24 h of admission,
      representation within 48 h, and Medical Emergency Response Team (MERT) calls
      within 24 h of admission. RESULTS: Two seasonally matched 26 week intervals were
      compared with adjustment for demographics, triage category and arrival by
      ambulance. Overall, there was an 18.4% rise in NEAT performance (95% confidence
      interval (CI): 17.7-19.1) while ED length of stay decreased by a total of 86.8
      min (95% CI: 83.6-90.1). Time series analysis did not suggest any preexisting
      trends to explain these results. The average time to referral decreased by 74.7
      min (95% CI: 69.8-79.6) and waiting times decreased across all triage categories.
      Rates of MERT activation and unplanned representation were unchanged. CONCLUSION:
      A facilitated team leader role for senior doctors can help to reduce length of
      stay by via early disposition, without significant risks to the patient.

PMID- 28455885
TI  - An extremely rare splice site mutation in the gene encoding complement factor I
      in a patient with atypical hemolytic uremic syndrome.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease
      characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute
      kidney failure. The disease is difficult to diagnose due to its similarity with
      other hematologic disorders, such as thrombotic thrombocytopenic purpura (TTP).
      However, genetic mutations are found in 50-70% of patients with aHUS and can be
      useful in its diagnosis. STUDY DESIGN AND METHODS: A 40-year-old male presented
      to our hospital with acute kidney injury, evidenced by high creatinine levels
      (8.3 mg/dL) and kidney biopsy results. The patient was preliminarily diagnosed
      with TTP and therapeutic plasma exchange (TPE) was initiated. After four
      treatments, TPE was discontinued due to lack of ADAMTS13 activity and inhibitor
      assay results that were not consistent with TTP, improved hematologic laboratory
      results, and aHUS genetic testing results. RESULTS: Next-generation sequencing
      showed a rare mutation at a splice site in the gene encoding complement factor I
      (CFI). Implication of this mutation in aHUS has not been previously described.
      Treatment with eculizumab reduced creatinine levels below 4.0 mg/dL, and the
      patient remained on maintenance dosage of eculizumab (1200 mg/14 days) to prevent
      aHUS recurrence. CONCLUSION: An extremely rare, heterozygous mutation in the gene
      encoding CFI likely affecting splicing was associated for the first time with
      aHUS. Sequencing was critical for rapid diagnosis and subsequent timely treatment
      with eculizumab, which resulted in improved renal function.

PMID- 28455886
TI  - Optimization of electrospray ionization conditions to enhance formation of doubly
      protonated peptide ions with and without addition of chromium(III).
AB  - RATIONALE: Production of multiply protonated ions by electrospray ionization
      (ESI) is important to the analysis of peptides by mass spectrometry. For small
      neutral and acidic peptides, addition of chromium(III) greatly increases the
      intensity of doubly protonated ions. The current study examines instrumental and
      solution parameters that maximize peptide ion charge by ESI. METHODS: The neutral
      and basic heptapeptides AAAAAAA (A7) and AAAKAAA (A3KA3) were used as test
      compounds and electrosprayed from a solution containing chromium(III) nitrate at
      a peptide to metal molar ratio of 1:10. Positive ion mode experiments were
      performed on a Bruker HCTultra PTM Discovery System quadrupole ion trap mass
      spectrometer. Source voltages and drying/nebulizer gases were systematically
      altered. The effects of rinsing, brand, and color of plastic microcentrifuge
      tubes (vials) employed were also investigated. RESULTS: Nebulizer gas pressure
      and drying gas flow rate are crucial parameters for production of [M + 2H]2+ ,
      while drying gas temperature alone has minimal effect. Optimization of the
      capillary exit and skimmer voltages are important both to maximize [M + 2H]2+ and
      reduce unwanted ion dissociation. Protonation is enhanced and fewer impurity
      peaks are observed when solutions are prepared in colorless plastic vials that
      have been rinsed briefly with propan-2-ol (isopropanol). CONCLUSIONS:
      Optimization of instrument and sample preparation factors for enhanced
      protonation with and without Cr(III) is necessary to allow maximum formation of
      [M + 2H]2+ . Proteomics researchers should find these procedures to be of use for
      increasing multiply protonated signal intensity even in the absence of Cr(III).
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 28455890
TI  - Editorial.
AB  - no summary.

PMID- 28455887
TI  - Human adipose stromal cell therapy improves survival and reduces renal
      inflammation and capillary rarefaction in acute kidney injury.
AB  - Damage to endothelial cells contributes to acute kidney injury (AKI) by causing
      impaired perfusion, while the permanent loss of the capillary network following
      AKI has been suggested to promote chronic kidney disease. Therefore, strategies
      to protect renal vasculature may impact both short-term recovery and long-term
      functional preservation post-AKI. Human adipose stromal cells (hASCs) possess pro
      angiogenic and anti-inflammatory properties and therefore have been tested as a
      therapeutic agent to treat ischaemic conditions. This study evaluated hASC
      potential to facilitate recovery from AKI with specific attention to capillary
      preservation and inflammation. Male Sprague Dawley rats were subjected to
      bilateral ischaemia/reperfusion and allowed to recover for either two or seven
      days. At the time of reperfusion, hASCs or vehicle was injected into the
      suprarenal abdominal aorta. hASC-treated rats had significantly greater survival
      compared to vehicle-treated rats (88.7% versus 69.3%). hASC treatment showed
      hastened recovery as demonstrated by lower creatinine levels at 48 hrs, while
      tubular damage was significantly reduced at 48 hrs. hASC treatment resulted in a
      significant decrease in total T cell and Th17 cell infiltration into injured
      kidneys at 2 days post-AKI, but an increase in accumulation of regulatory T
      cells. By day 7, hASC-treated rats showed significantly attenuated capillary
      rarefaction in the cortex (15% versus 5%) and outer medulla (36% versus 18%)
      compared to vehicle-treated rats as well as reduced accumulation of interstitial
      alpha-smooth muscle actin-positive myofibroblasts. These results suggest for the
      first time that hASCs improve recovery from I/R-induced injury by mechanisms that
      contribute to decrease in inflammation and preservation of peritubular
      capillaries.

PMID- 28455891
TI  - Paliperidone palmitate: effectiveness, safety, and the use for treatment of
      schizophrenia.
AB  - The aim of the study was to summarize the efficacy and tolerability of
      paliperidone palmitate, an atypical long-acting antipsychotic drug. Paliperidone
      is a 9-hydroxy metabolite of risperidone with a slightly different receptor
      profile and significantly different pharmacokinetic profile. After the short
      review of its pharmacological properties, the efficacy of the drug in comparison
      to placebo or to an active comparator was described. The studies revealed the
      effectiveness of paliperidone palmitate in the treatment of psychotic symptoms,
      mainly schizophrenia. The drug proved to be efficacious in both acute psychotic
      symptoms treatment and long-term treatment. Its efficacy in patients with
      schizophrenia was similar and sometimes even better than the efficacy of other
      long-acting drugs, such as risperidone or olanzapine. In the pharmacoeconomic
      studies, paliperidone proved to be cost-effective in comparison to risperidone or
      olanzapine. The review of the literature also underlined that paliperidone
      palmitate is well tolerated, compared with placebo. Frequency and severity of
      side-effects such as extrapyramidal symptoms, hyperprolactinemia and weight gain,
      was similar or less than those found in treatment with other atypical
      antipsychotics, including long-acting ones.

PMID- 28455892
TI  - Psychotic symptoms as a complication of electroconvulsive therapy - a case
      report.
AB  - We report a patient who experienced atypical symptoms in the course of
      electroconvulsive therapy (ECT). During ECT treatment patient experienced
      psychotic symptoms which should be differentiated with prolonged delirium and
      nonconvulsive status epilepticus. 46-year-old female was referred to hospital
      with a diagnosis of major depressive disorder with no psychotic features in the
      course of recurrent depression. Despite several changes of pharmacological
      treatment no improvement was achieved, therefore it was decided to initiate ECT.
      Physical and neurological examination revealed no deviations from the norm. The
      results of other tests (CT and EEG) were normal. 4 bilateral, bitemporal ECT
      procedures were performed. The course of each procedure was typical, the same
      doses of anesthetic medication and pulse dose was administered throughout all of
      the procedures. The duration of seizure was 32-40 s. Despite this mental symptoms
      observed during the course of the treatment differed from known to the authors
      from both their own experience and from literature. Delusions of reference,
      persecution, agitation, oneiric delusions and olfactory hallucinations which
      appeared after the 4th ECT session maintained for 14 days and resolved after
      treatment with olanzapine. To the best of our knowledge, this is the first report
      on delusions of reference and persecution, oneiric delusions and olfactory
      hallucinations associated with the course of ECT.

PMID- 28455893
TI  - The attitudes of psychiatrists toward people suffering from mental illnesses.
AB  - OBJECTIVES: Stigmatizing convictions, emotions and behaviors toward the mentally
      ill have impact on the social distance and more acute course of the illness.
      Research shows that the sufferers are the object of stigmatization also by
      representatives of medical professionals, including psychiatrists. The aim of the
      study was to examine the opinions of Polish psychiatrists regarding the mentally
      ill and to compare them with similar studies in the general population. METHODS:
      Polish psychiatrists were the investigated group. A diagnostic survey was
      conducted with a self-completion questionnaire. 232 questionnaires were analyzed.
      RESULTS: The results were compared with the general population. 61.5% of the
      respondents (59% in the general population) believe that a person who is mentally
      ill has a chance of recovery and 79% (vs. 77%) that coercion in Polish psychiatry
      is used frequently enough. 95% (vs. 75%) consider mental illness a health problem
      which is concealed from the others. 43% (vs. 56%) believe that mental illness
      significantly reduces the ability of regular employment, 13.5% (vs. 30%) believe
      that it reduces the ability to work in a team and 33% (vs. 71%) that it reduces
      the ability to do work which requires a lot of self-reliance. 16% (vs. 22%) is
      opposed to having institutions for the mentally ill near their place of
      residence. Psychiatrists more often declared a close friendship with people
      suffering from mental illness (87.5% vs. 32%), and a positive attitude toward the
      mentally ill and their participation in social life (86.5% vs. 65%). CONCLUSIONS:
      1. A relatively large group of the investigated psychiatrists compared with the
      general population has a family member suffering from a mental illness or they
      themselves suffer from mental illness. 2. Despite their education and
      professional mission, Polish psychiatrists present similarly stigmatizing
      attitudes toward the mentally ill as does the general population. 3. Through
      their attitudes, Polish psychiatrists co-create a support system, but also
      participate in the process of stigmatization.

PMID- 28455894
TI  - The influence of early psychosocial intervention on the long-term clinical
      outcomes of people suffering from schizophrenia.
AB  - OBJECTIVES: To compare the treatment outcomes of DSM-IV-TR schizophrenia patients
      in either a Community Treatment Program or an Individual Treatment Program (CTP
      vs. ITP). The assessment was made after the first hospitalization, and then after
      three and twelve years. METHODS: Participants were randomly assigned to CTP
      (experimental) and ITP (traditional) group, with 40 people in each group. 67
      people (84%) participated in all three assessments. The socio-demographic and
      clinical indicators were the same for both groups. In the first three years only
      the CTP group participated in day-care treatment, patient and family
      psychoeducation and community treatment. Later, both groups received this
      treatment. The following tools were used: Anamnestic and Catamnestic
      Questionnaire, the GAF scale, the BPRS LA and Lehman's Quality of Life Interview.
      RESULTS: It was only after twelve years that there was a significant beneficial
      improvement in the mean GAF score in the CTP group (p = 0.036), which was
      comparable with the results obtained by Watt and Shepherd for the course of the
      illness in favorable remission cases (p = 0.038). The difference in the number of
      relapses was also significantly in favor of the CTP group only after 12 years (p
      = 0.045), as was the difference in the number of rehospitalizations (p = 0.013).
      The general severity of symptoms was found to be significantly lower for the CPT
      group after 3 (p = 0.008) and 12 years (p = 0.030), whereas it was significantly
      lower in the case of positive syndrome only after 3 years (p = 0.044).
      CONCLUSIONS: 1. A greater number of favorable differences were identified for the
      CTP group at the twelve-year point than at the conclusion of the experiment. 2.
      The three-year delay in introducing psycho-social treatment was associated with a
      poorer long-term outcome for the clinical course of schizophrenia.

PMID- 28455895
TI  - Risk factors of anxiety and depressive symptoms in female patients experiencing
      intimate partner violence.
AB  - OBJECTIVES: The aim of the study was to find factors associated with higher
      severity of anxiety and depressive symptoms in female patients experiencing
      intimate partner violence (IPV). METHODS: The study was conducted in six randomly
      selected primary healthcare centers in Lublin province. The HADS (Hospital
      Anxiety and Depression Scale) and a structured questionnaire designed by the
      authors were administered to a total of 350 consecutive female patients visiting
      a GP. Fully completed questionnaire forms were obtained from 200 women. 102 (51%)
      participants who confirmed experiencing IPV ultimately made up the study cohort.
      Sequential models were created using backward stepwise multiple regression to
      investigate the potential risk and the protective factors associated with higher
      severity of anxiety and depressive symptoms in the study group. RESULTS: 68% and
      56% of the participants respectively had positive scores on the HADS anxiety and
      depression subscales. Living in a small town or in the countryside was associated
      with higher scores on the anxiety subscale (b = -1.18, p = 0.003), but not on the
      depression subscale. Chronic physical illness (b = 2.42, p = 0.013; b = 2.86, p =
      0.015), being unemployed (b = 0.58, p = 0.024; b = 0.69, p = 0.008), and exposure
      to economic violence (b = 3.97, p < 0.001; b = 3.88, p = 0.001) were associated
      with higher scores on both subscales of the HADS. The fact of receiving financial
      support (b = 2.67, p = 0.002; b = 2.68, p = 0.003) was a protective factor
      against both kinds of symptoms. Exposure to physical violence was associated with
      higher scores on the depression subscale (b = 3.09, p = 0.005), but not on
      anxiety subscale. CONCLUSIONS: The type of violence and socioeconomic
      characteristics were more strongly associated with anxiety and depressive
      symptoms in women experiencing IPV than demographic variables.

PMID- 28455896
TI  - Sexual problems in homo- and bisexual men - the context of the issue.
AB  - The aim of the paper is to present a specific context for the occurrence of
      sexual problems, i.e., sexual dysfunction in the population of homo - and
      bisexual men. Sexual problems and revealing them are usually a big challenge for
      men. In case of homo - and bisexual men additional psychological and social
      factors may contribute to the occurrence of these problems, as well as make
      experiencing them more painful, but also impede looking for and receiving an
      adequate help. These factors are connected to the specific features of gay men
      sexuality, such as: lack of obvious sexual scripts for homosexual men, full
      reversibility of all sexual roles and positions in contacts between two men or no
      fear of unwanted pregnancy, but also with the unique psychosocial context such
      as: minority stress and internalized homophobia. Clinicians - psychiatrists,
      sexologists and psychologists - should be aware of their existence to deliver a
      more effective professional and culturally competent care, which is free of
      prejudice, based on deepened reflection and void of automatic transference of
      experiences with work with heterosexual men.

PMID- 28455897
TI  - Sexual dysfunctions in non-heterosexual men - literature review.
AB  - The paper aims to present results and discuss methodology of research conducted
      so far on sexual dysfunction in non-heterosexual men, as well as to form
      suggestions for future research and clinical practice. The present paper is a
      continuation of our earlier paper, which discussed the specific context of the
      issue connected with the characteristics of gay sexual orientation and the social
      situation those men face. There is little research on dysfunctions and sexual
      problems in non-heterosexual men, and none has been conducted in Poland. The
      research that has been done is characterized by inconsistent methodology that is
      far from perfect, and varied results which cannot be compared. There are still
      many unanswered questions in the field. The issues connected with research that
      require attention include the choice of samples and their representativeness, and
      the accuracy of the methods used for identifying sexual dysfunctions. It is also
      still not clear whether sexual problems occur more often in non-heterosexual than
      heterosexual men, how non-heterosexual men deal with those problems, and how the
      problems influence their functioning. Another issue that requires a deeper
      understanding is the connections between sexual dysfunctions in this group and
      various aspects of the so-called minority stress, such as internalized homophobia
      and experiencing discrimination, psychoactive substance abuse, HIV infection, and
      the sexual and partnership lifestyle.

PMID- 28455898
TI  - Polish adaptation of Sexual Addiction Screening Test - Revised.
AB  - OBJECTIVES: Addictive sexual behaviours are gaining more and more attention from
      researchers. There are actually 25 different questionnaires for assessing the
      level of loss of control over sexual. The main aim of this work was to make such
      an adaptation of the Sexual Addiction Screening Test-Revised (SAST-R; the most
      popular and questionnaire). behaviours (LoCoSB). None of them have been adapted
      and validated in a Polish language version. METHODS: For the purpose of
      psychometric features examination and validation of the Polish version of SAST-R
      (SAST-PL-M), we recruited 116 heterosexual men receiving psychological treatment
      due to LoCoSB and meeting the criteria for hypersexual disorder. The control
      group consisted of 442 heterosexual males having never looked for any
      psychological or psychiatric help due to LoCoSB. RESULTS: SAST-PL-M has high
      reliability (Cronbach's alpha = 0.904) and good filtering characteristics for
      identification of people who are potentially experiencing difficulty with control
      over sexual behaviours (the ROC curve for a threshold of 5 out of a maximum 20
      points is characterised by a sensitivity of 99.1% and a specificity of 78.3%).
      CONCLUSIONS: SAST-PL-M can be used as an efficient screening test for symptoms of
      LoCoSB in clinical and research setups. Results below 5 points indicate a high
      probability of no problems, while more than 5 points can indicate the need for
      additional clinical interviews. SAST-PL-M results may be successfully referred to
      the results of SAST-R when used with heterosexual male populations for research
      purposes.

PMID- 28455899
TI  - Persistent genital arousal disorder - a case report.
AB  - The persistent genital arousal disorder (PGAD) may coexist with restless legs
      syndrome and overactive bladder syndrome and share some similarities with these
      conditions. Thus, the new term: restless genital syndrome (RGS) is proposed. The
      purpose of this paper is to present a case of PGAD, including the description of
      the etiology, the diagnostics and the treatment of the disorder. The described
      patient meets the criteria for PGAD. Organic lesions within nervous and
      urogenital system were excluded and the psychogenic background of the syndrome
      was assumed in this case. The patient was diagnosed with personality disorder
      with a predominance of dependent personality traits and emotional lability. After
      the failure of pharmacological treatment, systemic psychotherapy with cognitive
      behavioral elements was initiated with moderate effect.

PMID- 28455900
TI  - Barriers in the access to alcohol treatment in outpatient clinics in urban and
      rural community.
AB  - OBJECTIVES: The aim of the study was identification of the barriers making it
      notably more challenging to access clinics in urban and rural communities.
      METHODS: The method, which was used in this study adopts the qualitative research
      perspective. The research tool was an interview with a standardized list of
      desired information. The interviews were conducted with alcohol dependent
      patients and therapists. 64 interviews were performed in two outpatient clinics
      located in Warsaw, and in rural area. RESULTS: Respondents identified similar
      barriers for the clinics located in Warsaw and in the rural community. Those
      were: shame associated with seeking help, waiting time for stationary support,
      meeting intensity, and general clinic condition. Barriers identified by
      respondents from Warsaw were associated with long waiting time for outpatient
      treatment and individual appointment, therapeutic offer excluding deaf and
      mentally ill individuals from the therapy, and unattractive program requiring
      complete abstinence. Barriers in access to treatment spotted by the respondents
      from the rural community related to the lack of anonymity of treatment associated
      with too low number of clinics in the district, lack of choice in terms of
      preferred facility, commutation time and costs, as well as no inter-institutional
      cooperation. CONCLUSIONS: The barriers identified in the study were similar to
      the ones specified in the research conducted in Poland in the 1990s, and at the
      end of first decade of 21st century. Barriers were psychological in character and
      had the form of internal withdrawal and anxiety to start treatment. Certain
      structural barriers were indicated as well.

PMID- 28455901
TI  - Social networks and social functioning level among occupational therapy workshops
      and community-based support centers users.
AB  - OBJECTIVES: Community-Based Support Centers (CSC) and Occupational Therapy
      Workshops (OTW) have been functioning for over 20 years in Poland. However, the
      effectiveness of their rehabilitation programs as well as the users profile has
      not been examined yet. The aim of the study was to determine social functioning
      level and support network effectiveness of CSC and OTW users. METHODS: Research
      tools: GAS (Global Assessment Scale), social network and social support
      assessment, Social Functioning Scale, Sociodemographic Questionnaire. RESULTS:
      Results show that investigated groups (except for participants' age) show no
      significant differences in sociodemographic variables and illness profile.
      Significant differences were found in the aspect of number and quality of support
      networks and the functioning level. CONCLUSIONS: Analyzed support institutions
      have different aims and offer different support programs which show differences
      in support networks and social functioning level. It can result from that the
      goal of OTW is to activate its users and assist them with their reintegration
      into the labor market, whereas CSCs are oriented on users' current issues and
      hospitalization prevention. It is important to have knowledge of these specifics
      during referring a person to such service.

PMID- 28455902
TI  - Letter to Editor. Depression and cytokines - a different perspective. Author's
      response.
AB  - no summary.

PMID- 28455903
TI  - The physiological phosphorylation of tau is critically changed in fetal brains of
      individuals with Down syndrome.
AB  - AIMS: Down syndrome (DS) is a common cause of mental retardation accompanied by
      cognitive impairment. Comprehensive studies suggested a link between development
      and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like
      pathology. However, there is still a paucity of data on tau in early DS to
      support this notion. METHODS: Using morphometric immunohistochemistry we compared
      tau phosphorylation in normal brains and in brains of individuals with DS from
      early development until early postnatal life. RESULTS: We observed in DS a
      critical loss of physiological phosphorylation of tau. Rhombencephalic structures
      showed prominent differences between controls and DS using antibodies AT8 (Ser
      202/Thr-205) and AT180 (Thr-231). In contrast, in the subiculum only a small
      portion of controls deviated from DS using antibodies AT100 (Thr-212/Ser-214) and
      AT270 (Thr-181). With exception of the subiculum, phosphorylation-independent tau
      did not differ between groups, as confirmed by immunostaining for the HT-7
      antibody (epitope between 159 and 163 of the human tau) as well. DISCUSSION: Our
      observations suggest functional tau disturbance in DS brains during development,
      rather than axonal loss. This supports the role of tau as a further important
      player in the pathophysiology of cognitive impairment in DS and related AD.

PMID- 28455904
TI  - The Structure of the Elusive Simplest Dipeptide Gly-Gly.
AB  - Among the hundreds of peptide compounds for which conformations have been
      determined by using different spectroscopic techniques, the structure of the
      simplest dipeptide glycylglycine (Gly-Gly) is conspicuously absent. Herein, for
      the first time, solid samples of Gly-Gly have been vaporized by laser ablation
      and three different structures have been revealed in a supersonic expansion by
      Fourier transform microwave spectroscopy. The intramolecular hydrogen bonding
      interactions that stabilize the observed forms have been established based on the
      14 N nuclear quadrupole hyperfine structure. We have illustrated how conformer
      interconversion distorts the equilibrium conformational distribution, giving rise
      to missing conformers in the conformational landscape.

PMID- 28455905
TI  - RE: Futyma et al. use of uroflow parameters in diagnosing an overactive bladder
      Back to the drawing board and ICS News 613.

PMID- 28455906
TI  - The Need for an Alternative to Radicals as the Cause of Fragmentation of a
      Thiamin-Derived Breslow Intermediate.
AB  - Mandelylthiamin (1) is a conjugate of benzoylformate and thiamin that loses CO2
      to form the classic Breslow intermediate (2), whose expected fate is formation of
      the thiamin conjugate of benzaldehyde (3). Surprisingly, it was observed that 2
      decomposes to 4 and 5 and rearranges to 6 in competition with the expected
      protonation to give 3. Recent reports propose that the alternatives to
      protonation arise from homolysis followed by radical-centered processes. It is
      now found, instead, that the spectroscopic observations cited in support of the
      proposed radical pathways are likely to be the result of other events. An
      alternative explanation is that ionization of the enolic hydroxy group of 2 and
      resultant electronic reorganization leads to C-C bond cleavage and non-radical
      intermediates that readily form 4, 5, and 6.

PMID- 28455907
TI  - The Effect of Surface Site Ensembles on the Activity and Selectivity of Ethanol
      Electrooxidation by Octahedral PtNiRh Nanoparticles.
AB  - Direct ethanol fuel cells are attractive power sources based on a biorenewable,
      high energy-density fuel. Their efficiency is limited by the lack of active anode
      materials which catalyze the breaking of the C-C bond coupled to the 12-electron
      oxidation to CO2 . We report shape-controlled PtNiRh octahedral ethanol oxidation
      electrocatalysts with excellent activity and previously unachieved low onset
      potentials as low as 0.1 V vs. RHE, while being highly selective to complete
      oxidation to CO2 . Our comprehensive characterization and in situ electrochemical
      ATR studies suggest that the formation of a ternary surface site ensemble around
      the octahedral Pt3 Ni1 Rhx nanoparticles plays a crucial mechanistic role for
      this behavior.

PMID- 28455908
TI  - The Sapir-Whorf hypothesis and inference under uncertainty.
AB  - The Sapir-Whorf hypothesis holds that human thought is shaped by language,
      leading speakers of different languages to think differently. This hypothesis has
      sparked both enthusiasm and controversy, but despite its prominence it has only
      occasionally been addressed in computational terms. Recent developments support a
      view of the Sapir-Whorf hypothesis in terms of probabilistic inference. This view
      may resolve some of the controversy surrounding the Sapir-Whorf hypothesis, and
      may help to normalize the hypothesis by linking it to established principles that
      also explain other phenomena. On this view, effects of language on nonlinguistic
      cognition or perception reflect standard principles of inference under
      uncertainty. WIREs Cogn Sci 2017, 8:e1440. doi: 10.1002/wcs.1440 For further
      resources related to this article, please visit the WIREs website.

PMID- 28455909
TI  - Emergency department utilization in pediatric heart transplant recipients.
AB  - We used the NEDS database (2010) to evaluate ED utilization in PED HT recipients
      compared to other patient populations with focus on characteristics of ED visits,
      risk factors for admission, and charges. We analyzed 433 ED visits by PED HT
      recipients (median age 8 [range: 0-18] years). The most common primary diagnosis
      category was infectious (n=163, 37.6%), with pneumonia being the most common
      infectious etiology. When compared to all PED visits, HT visits were more likely
      to result in hospital admission (32.6% versus 3.9%, P<.001), had greater hospital
      LOS (median of 3 days [IQR 2-4] versus 2 days [IQR 1-4], P=.001), and accumulated
      greater total hospital charges (median $26 317 [IQR $11 438-$46 407] versus $12
      332 [IQR $7092-$22 583], P<.001). When compared to visits by other SOT
      recipients, results varied with similar rates of hospital admission for HT,
      LUNGT, and KT visits and similar LOS for HT and KT visits but differing total
      hospital charges. Although PED HT recipients account for a small percentage of
      overall ED visits, they are more likely to be hospitalized and require greater
      resource utilization compared to the general PED population, but not when
      compared to other SOT recipients.

PMID- 28455910
TI  - Delayed Dialyzer Reprocessing for Home Hemodialysis.
AB  - Although dialyzer reuse for home hemodialysis (done by patients at home) has been
      in practice since the 1960s, it is now almost completely abandoned. The need for
      dialyzer reuse resurfaced with the renewed interest in daily/nightly forms of
      home hemodialysis and the associated increase in operating costs. We describe a
      method of dialyzer reuse based on reprocessing of dialyzers at the center, after
      they had been stored in a refrigerator at home for 1 week by the patient.
      Transportation of the dialyzers by either the patient or a transportation service
      was acceptable to the patients. Despite the lower number of reuses, possibly
      related to the delayed processing, dialyzer reuse in this setting provided
      significant financial benefits. Experience with this process for 3 years has not
      disclosed any negative effects after the initial logistical issues related to
      dialyzer transportation were resolved. In summary, weekly dialyzer reprocessing
      at the center provides a solution to the need for dialyzer reuse for the home
      hemodialysis patient.

PMID- 28455911
TI  - Concentrated Sodium Citrate (23%) for Catheter Lock.
AB  - For chronic central venous dialysis catheters, the standard method for
      maintaining catheter patency between treatments is to instill (lock) catheters
      with 5000 - 10 000 units of heparin in each lumen. Sodium citrate (citrate) is an
      anticoagulant with intrinsic antibacterial activity (at 20% concentration or
      higher). Citrate has only transient anticoagulant effects if accidentally infused
      to the patient. Prior studies of citrate as a catheter lock solution have
      utilized citrate concentrations of 1% in combination with 27 mg/mL gentamicin. We
      changed clinical protocols for catheter locks using various solutions, including
      concentrated citrate, in a dialysis unit with 50% of patients having chronic
      central venous catheters [40 catheters total, mostly Ash Split Cath (Medcomp,
      Harleysville, PA, U.S.A.) but some Tesio (Medcomp) and Hickman (BARD, Salt Lake
      City, UT, U.S.A.) catheters]. At 3- to 4-month intervals, the standard catheter
      lock solution for the unit was varied on the following schedule: heparin; 10%
      citrate with 3 mg/mL gentamicin; 20% citrate with 3 mg/mL gentamicin; heparin;
      and 23% citrate. Catheters were not routinely removed during treatment of
      bacteremia. Incidence of bacteremia in patients with catheters using heparin as
      catheter lock was 4.32 episodes per 3000 patient-days (equivalent to percent of
      patients with catheters having bacteremia per month). The incidence of bacteremia
      decreased to 1.68 using 20% citrate/gentamicin as catheter lock (p < 0.05) and to
      0% with 47% citrate (p < 0.05). Incidence of bacteremia increased on return to
      heparin and decreased again with use of 23% citrate to 1.79 (p < 0.05). Use of
      urokinase for occluded catheters also significantly decreased with citrate during
      the time that it was available (p = 0.02). Life table analysis indicated an 83%
      survival of Ash Split Cath catheters at 1 year, in this unit. Concentrated
      citrate is an effective catheter lock solution that may provide prolonged central
      venous catheter use with a diminution in catheter-related infections and
      occlusion.

PMID- 28455912
TI  - Does Blood Pressure Control by Gentle Ultrafiltration Improve Survival in
      Hemodialysis Patients?
AB  - Agentle ultrafiltration can be achieved using a long and slow hemodialysis. It is
      easier to achieve gentle ultrafiltration if the interdialytic weight intake is
      moderate ( i.e., if the patient maintains a low sodium diet) and if diffusion
      allows for a negative or nil sodium balance during the session ( i.e., dialysate
      sodium < 140 mmol/L). A gentle ultrafiltration allows control of blood pressure
      by reducing the extracellular volume to its ideal level, the "dry weight," at the
      end of the session. Controlling blood pressure reduces cardiovascular mortality,
      which is by far the foremost cause of death in hemodialysis. Controlling blood
      pressure means reducing the occurrence of both hypertension and hypotension.
      Hypotension has been reported to correlate with mortality in hemodialysis as much
      as or more than hypertension itself. This "U-curve" phenomenon is not
      paradoxical. It displays two distinct facts on the same figure: an increased
      early mortality in hypotensive patients (hypotension is a marker of frailty or
      congestive heart failure, both of which cause increased mortality) and, on the
      other hand, the well-established, long-term increased mortality in hypertensive
      patients. Hypotension is not a mandate to undertreat hypertension.

PMID- 28455913
TI  - Use of Systemic Blood Urea Nitrogen Levels Obtained 30 Minutes before the End of
      Hemodialysis to Portray Equilibrated, Postdialysis Blood Urea Nitrogen Values.
AB  - Blood urea nitrogen (BUN) levels obtained at 30 minutes before the end of
      dialysis were found to be closely similar to equilibrated, postdialysis BUN
      values obtained 30 minutes after the end of dialysis. Because of this similarity,
      the former BUN values can be used to derive equilibrated urea reduction ratio, or
      equilibrated Kt/V instead.

PMID- 28455914
TI  - What Went Wrong with Home Hemodialysis in the United States and What Can Be Done
      Now?
AB  - In 1973, almost 40% of the more than 10 000 dialysis patients were treated by
      home hemodialysis. Today, with more than a quarter of a million dialysis patients
      in the United States, fewer than 2000 are on home hemodialysis. A number of
      factors have contributed to this change. First, many nephrologists and
      administrators who were developing new dialysis units had little or no practical
      experience with dialysis for chronic renal failure. Second, more elderly and
      diabetic patients were admitted to treatment. Home hemodialysis was more
      difficult for such patients, and often their helpers were themselves were
      elderly. Third, hemodialysis machines were difficult to learn and operate.
      Fourth, following publication of the results of the National Cooperative Dialysis
      Study, there developed the erroneous concept that a Kt/V equal to 1.0 was
      "adequate dialysis." As bigger dialyzers became available, there was a widespread
      shortening of dialysis time. This decrease in time was embraced by for-profit
      dialysis facilities and inadequately educated patients, and assembly-line
      dialysis became generally accepted. Finally, continuous ambulatory peritoneal
      dialysis, with its simplicity and short training time, began to fill the need of
      many patients for home dialysis and independence, at least temporarily.
      Fortunately, the trend is now reversing. Two developments clearly have benefits
      for home hemodialysis. The first is an increasing interest in the use of more
      frequent dialysis. The second is the development of new equipment designed
      specifically for use by the patient, and requiring a minimum of effort on the
      patient's part.

PMID- 28455915
TI  - Stepwise Anticoagulation with Warfarin for Prevention of Intravenous Catheter
      Thrombosis.
AB  - Warfarin is the most commonly used anticoagulant for prevention and therapy of
      thrombosis. Warfarin is a vitamin K antagonist and inhibits synthesis of clotting
      factors II, VII, IX, and X, and anticoagulant proteins C and S. Whereas there is
      extensive information about the efficacy of warfarin and target International
      Normalized Ratio (INR) for patients with artificial heart valves, atrial
      fibrillation, pulmonary emboli, deep venous thrombosis, and lupus anticoagulant,
      there is little in the literature on the role of warfarin in maintaining the
      patency of hemodialysis catheters. Much more is reported about the value of
      minidose warfarin in maintaining the patency of infusion catheters. Many centers
      have tried low-dose warfarin (1 mg per day), and found this not to be effective
      in preventing catheter thrombosis in many patients. Although most support the use
      of warfarin following catheterproblems, individual units have their own
      guidelines, with doses ranging from 2 mg per day (normal INR) to formal systemic
      anticoagulation with INR from 1.5 to 3.0. Stepwise anticoagulation with warfarin
      is emerging as useful in preventing catheter-associated thrombosis. With this
      method, patients are placed on low-dose warfarin after the first clotting
      episode. With each subsequent episode, the dose is increased, raising INR by 0.5
      until clotting episodes do not recur. Warfarin doses similar to those in patients
      with artificial heart valves have been used in selected patients (target INR 3.0 
      4.0) to prevent clotting.

PMID- 28455916
TI  - Is Hypertension Beneficial to the Conventional Hemodialysis Patient?
AB  - Hypertension is common in the conventional hemodialysis population. While
      hypertension in the general population has been shown to reduce survival, the
      issue is less clear in the dialysis population. This review focuses on recent
      studies showing a favorable outcome in hypertensive hemodialysis patients
      compared to those with lower blood pressure. Possible explanations for this
      paradoxical relationship are examined and practical suggestions given for the
      management of hypertension in the hemodialysis patient.

PMID- 28455917
TI  - Laudatio: Professor Carl Magnus F. T:son Kjellstrand.

PMID- 28455918
TI  - The Case for Every-Other-Day Dialysis.
AB  - Until daily dialysis becomes widely available, we believe that hemodialysis
      patients would benefit enormously from every-other-day dialysis (EODD), which may
      be implemented both by home patients and in centers. Benefits of EODD over the
      routine, three-times-weekly schedule would include decreased mortality after the
      weekend interval without dialysis; increased weekly dose of dialysis, resulting
      in better rehabilitation; and improved blood pressure control.

PMID- 28455919
TI  - Outpatient High-Dose Urokinase Infusion Improves Dialysis Catheter Longevity: A
      Prospective Observational Study.
AB  - Catheter thrombosis is a major limiting factor affecting catheter survival in
      hemodialysis (HD). A previous retrospective study highlighted the utility of
      outpatient intradialytic high-dose urokinase (HDU) infusion in the treatment of
      HD catheter thrombosis. The present study was designed to prospectively evaluate
      the effectiveness of 250 000 IU urokinase given as a 3-hour infusion during HD.
      The infusion would follow detection of a drop in blood flow thought to be
      secondary to thrombosis [a "thrombotic event" (TE)] after exclusion of
      nonthrombotic causes of drop in blood flow [a "nonthrombotic event" (NTE)], such
      as systemic hypotension or suboptimal position of the catheter on x ray. An
      "event" was defined as a drop in pump blood flow by greater than or equal to 20%
      of the prescribed blood flow. Twenty patients (mean age 57.7 years; 13 males)
      with documented or potentially long-term catheters were recruited (total
      catheters used, 30) from an outpatient HD unit. A variety of catheter types were
      used. Catheter position was confirmed on x ray. Hemodialysis sessions were
      monitored for 6 months or until catheter removal (whichever was earlier).
      Thrombotic and NTEs (mostly related to drop in blood flow) were noted. The use of
      intradialytic HDU infusions was monitored. Improvement was defined as
      reestablishment of blood flow to within 10% of prescription. There were 24 TEs in
      11 patients and 15 NTEs in 7 patients. Twenty-one of 22 (95%) TEs responded to
      HDU, with complete restoration of blood flow; in 1/22 HDU-treated instances there
      was a partial response. For 2/24 TEs the patients underwent catheter stripping
      with good results. Twelve of 15 NTEs occurred in the first 2 weeks of catheter
      placement versus 6/24 TEs (p = 0.001, chi-square). Catheter survival was longer
      than 24 weeks in 12/30 catheters. Nine catheters were lost to NTEs. No catheter
      was lost secondary to a TE. It is therefore concluded that intradialytic
      outpatient HDU is useful for the treatment of HD catheter thrombosis. It may
      obviate/reduce the need for catheter stripping or replacement. Randomized
      controlled trials with this approach are needed. A higher proportion of NTEs
      tended to occur earlier after catheter placement compared to TEs.

PMID- 28455920
TI  - Why Our Patients Like Daily Hemodialysis.
AB  - The option of daily hemodialysis (HD) was discussed in November 1998 with a group
      of 35 HD patients on home or self-care/limited-care HD in a single, freestanding
      unit. After the meeting, 3 patients on home HD chose to switch to daily HD. The
      clinical success of the first patient and the immediate followers was one of the
      main reasons for further extension of this experience. At the time of this
      writing (February 2000), 10 patients were on a daily HD program (8 at home and 2
      in a self-care/limited-care center) and one was in training for home daily HD.
      One further patient who tried 1 month of daily HD dropped out for logistic
      reasons. On daily HD, patients are dialyzed 2 - 3 hours/day, 6 days/ week, with
      blood flow of 270 - 300 mL/min, on bicarbonate dialysate with individually
      determined levels of Na and K. The schedule is flexible and a switch to 3 - 4
      dialyses/week is occasionally allowed for working needs or for vacation. In
      addition to the well-known clinical advantages (better well-being, blood pressure
      control, nutrition, etc.), some patients preferred daily HD because of easier
      organization of daily activities, including work schedule. Patients initially
      feared frequent needle punctures and excessive burden on partners, but those
      concerns proved to be less a problem than anticipated. All current patients are
      willing to continue daily HD; only a nursing shortage limits further extension of
      the program in the self-care/limited-care center.

PMID- 28455921
TI  - Effect of Valsalva Maneuver on QT Dispersion in Hemodialysis Patients.
AB  - Increased QT dispersion seems to be related to an increased risk of arrhythmia
      and sudden death, a common cause of mortality in hemodialysis (HD) patients.
      Increase in sympathetic tone has been documented in HD patients. In this study,
      we aimed to investigate the effect of changes in the autonomic tone on QT
      dispersion (QTd) in HD patients. Twenty HD patients (M/F 13/7; age, mean +/-SD,
      28 +/- 10 years) and 22 age- and sex-matched healthy controls (M/F 12/10; age, 30
      +/- 10 years) were included. The patients were dialyzed three-times weekly; time
      on dialysis was 17 +/- 8 months. The QT durations were measured from 12 lead
      surface EKGs and were corrected for RR intervals. Corrected maximum (QTc max) and
      minimum (QTc min) QT intervals and their difference (QT c d) were recorded. The
      effect of the Valsalva maneuver in the release phase on QT c intervals and
      dispersion was assessed. The HD patients had prolonged values compared to
      controls: QT c d, 59 +/- 17 ms versus 35 +/- 7 ms, p < 0.001; QT c max, 458 +/-
      41 ms versus 397 +/- 21 ms, p < 0.001; and QT c min, 398 +/- 36 ms versus 362 +/-
      25 ms, p < 0.001. After the Valsalva maneuver no changes were observed in
      controls: QT c max, 397 +/- 21 ms versus 396 +/- 22 ms, p = 0.9; QT c min, 362 +/
      24 ms versus 358 +/- 19 ms, p = 0.5; and QT c d, 35 +/- 7 ms versus 38 +/- 10
      ms, p = 0.15. Whereas, in HD patients all values were significantly shortened:
      QTc max, 458 +/- 41 ms versus 427 +/- 35 ms, p = 0.003; QTc min, 398 +/- 36 ms
      versus 379 +/- 34 ms, p = 0.04; and QTc d, 59 +/- 17 ms versus 48 +/- 15 ms, p =
      0.01. The decrease in QTmax was more prominent than the decrease in QTmin, hence
      QT dispersion was significantly decreased after the Valsalva maneuver, but
      differences from controls were still significant. In conclusion, increased
      sympathetic activity may have a role in the prolonged QT duration and increased
      QT dispersion in HD patients.

PMID- 28455922
TI  - Continuous Blood Volume Monitoring and Ultrafiltration Control.
AB  - Continuous blood volume monitoring (CBVM) is believed to be a promising method
      for making the determination of patients' "dry weight" more objective, and
      ultrafiltration (UF) control more appropriate. Although blood volume response to
      UF and the interrelation between blood volume changes and changes in hemodynamic
      parameters are highly individual, certain principles of this response and
      interrelation can be identified and exploited for effective use of CBVM. The
      present work summarizes the authors' findings from practical CBVM application
      over the past 5 years and their opinions on the future development of this
      method. Four distinct types of blood volume response to constant UF rate were
      identified: Type 1, flat line throughout the whole session; Type 2, flat line
      during the first part of dialysis, followed by a linear decrease during the
      remaining time; Type 3, linear decrease right from dialysis start; and Type 4,
      linear decrease first, followed by a flat line during the remaining time. The
      possibility of a shift from one type to the other was verified. Blood volume
      reduction due to UF was found to have a static and a dynamic component. The most
      important factors affecting both components were found to be, by sensitivity
      analysis of a three-pool kinetic model, degree of overhydration, vascular system
      compliance, and UF volume (for the static component); and UF coefficient of the
      capillary wall and UF rate (for the dynamic component). Type 3 response, induced
      by more vigorous UF, was found to significantly decrease the volume of residual
      daily diuresis on the first postdialysis day. If confirmed, this finding may
      serve as a basis for the response type choice in patients with still significant
      residual renal function. Exploitation of the existence of dynamic blood volume
      reduction component for the first generation of automated biofeedback UF
      controllers may be complemented by automated identification of patient's plasma
      refilling capacity and/or position of his/her point on the Guytonian
      pressure/volume characteristics curves, and thus may more advanced "intelligent"
      UF controllers be constructed in the future.

PMID- 28455923
TI  - Blood Access Outcomes Associated with Short Daily Hemodialysis.
AB  - With the growing number of reports that daily hemodialysis (DHD) improves
      clinical outcomes and quality of life, there has been increased interest in the
      effects of more frequent venipunctures on blood accesses. Since 1996, we have
      converted 30 patients (27 in-center, 3 home) from conventional 3/week dialysis to
      short, daily, 6/week dialysis (sDHD). Twenty-five patients started for medical
      indications. End-stage renal disease (ESRD) causes were diabetes mellitus (in 7),
      hypertension (6), glomerulonephritis (8), hereditary nephritis (2), and other
      (7). Mean (+/-SD) age was 57 +/- 16 years. Patients had an average of 3.8 major
      comorbidities in addition to ESRD. Thirty patients were followed on sDHD for 388
      patient-months: 9 patients died after 4.2 +/- 6.7 months, 3 were transplanted at
      5.4 +/- 2.2 months, and 3 were disenrolled at 9.3 +/- 10.5 months. Fifteen
      patients remain on sDHD at 20.4 +/- 14.1 months. Access problems for the 12
      months prior to sDHD were compared to those that occurred while the patient was
      on sDHD. Problems were tracked by access type. There were 40 different accesses
      in 30 patients with a cumulative 28.07 access-years pre-DHD; 24 of these accesses
      were artificial bridge grafts (ABG) of either polytetrafluoroethylene or bovine
      material. There were 27 access problems pre-DHD, or 0.962 problems per access
      year. On sDHD these same 30 patients had 41 accesses for 34.44 access-years; 23
      of these were ABGs. There were 31 access problems or 0.900 problems per access
      year. There were no significant differences in access problems comparing pre-DHD
      with on-sDHD, either in aggregate or when analyzed by access type. After 39
      months of observation, there does not appear to be an increase in blood access
      problems when patients are converted from conventional dialysis to sDHD.

PMID- 28455924
TI  - Thrombolytic Agents.
AB  - Thrombus dissolution is dependent on activators of plasminogen, the principal
      enzyme of fibrinolysis, reaching plasminogen bound to the surface of fibrin, and
      overcoming the many inhibitors of clot lysis present in the plasma milieu. In
      dialysis patients with occluded catheters and grafts, three activators -
      streptokinase, urokinase, and tissue plasminogen activator (tPA) - have been
      used. Streptokinase has fallen out of favor because of its adverse effect
      profile; urokinase has been the mainstay of therapy. Urokinase has been used
      alone and in conjunction with mechanical methods for clearance of thrombi from
      arteriovenous grafts. It has also been instilled into occluded central venous
      catheters, but often is more effective if given systemically during dialysis in
      order to lyse the fibrin sheath that surrounds the catheter tip. Due of
      manufacturing problems, urokinase is no longer available and management with tPA
      is being actively investigated. One small trial showed that recombinant tPA was
      significantly more effective than urokinase for restoring catheter patency, but
      the drug is not yet approved for this purpose by the FDA, and current packaging
      is not optimal. The problems with thrombolytic agents may be obviated in the
      future by better methods of prevention of thrombus formation, monitoring flow to
      anticipate occlusion, and early mechanical interventions to restore patency.

PMID- 28455925
TI  - Volume Control in Hemodialysis Patients.
AB  - Cardiovascular disease is the main cause of the high mortality of dialysis
      patients and is largely due to poor control of blood pressure. Establishing and
      maintaining normal extracellular volume (ECV) is required to achieve
      normotension. The dry weight concept links ECV and blood pressure by a simple
      clinical relationship. Dry weight is the ideal postdialysis weight that allows a
      constantly normal blood pressure to be maintained without using antihypertensive
      medications. Maintenance of normal ECV requires control of salt intake to reduce
      interdialytic weight gain ( i.e., saline overload) combined with the diffusive
      and convective removal of salt and water from the body during dialysis sessions.
      Several problems are to be faced when using the dry weight method. Clinical
      evaluation must take into account the following confounding factors: weight
      varies with nutrition, clinical symptoms are unspecific and sometimes discordant,
      and there is a lag time between ECV and blood pressure changes. On the other
      hand, achievement of dry weight is hampered by dialysis times that are too short
      (and weight gains that are too high), by antihypertensive medications, and by
      poor heart conditions. A longer session time allows for a slower, easier, and
      more comfortable ultrafiltration.

PMID- 28455926
TI  - Central Venous Catheters for Hemodialysis: How to Overcome the Problems.
AB  - The use of central venous dialysis catheters is increasing in clinical practice.
      These devices, although relatively easy to insert, do have problems. Catheter
      size limits the amount of dialysis that can be delivered. Central venous
      hemodialysis catheters minimize cardiopulmonary recirculation, but have increased
      potential for access recirculation compared to native or artificial arteriovenous
      (AV) fistulas and grafts. Developments in catheter design and optimal positioning
      have improved the amount of dialysis that can be delivered. Similarly, infection
      rates are improving with careful attention to peri-insertion care and the use of
      topical antiseptics and antibiotics. Although catheter thrombus remains a
      problem, the introduction of recombinant tissue plasminogen activator and
      mechanical dislodgement with an endoluminal brush have improved patency rates,
      but some patients may require long-term warfarin therapy.

PMID- 28455927
TI  - Laudatio: Dr. Belding H. Scribner.

PMID- 28455928
TI  - Outcomes of Severe Methanol Intoxication Treated with Hemodialysis: Report of
      Seven Cases and Review of Literature.
AB  - To identify factors associated with the outcome of severe methanol intoxication
      treated with hemodialysis, we analyzed the clinical course of 7 patients admitted
      with serum methanol level higher than 50 mg/dL, and therefore requiring
      hemodialysis. Four patients (group A) had adverse outcomes (1 death, 3 severe
      neurological deficits and/or blindness) and 3 patients (group B) had no adverse
      outcomes. Compared to group B, group A appeared to have a longer delay between
      ingestion of methanol and arrival at the emergency department (ED), a longer wait
      in the ED until ethanol infusion was started (3.6 +/- 2.7 vs 1.3 +/- 0.9 hr, p <
      0.05), and, on admission, higher serum methanol (504 +/- 219 vs 321 +/- 228
      mg/dL, p < 0.05), higher serum osmolality (460.5 +/- 98.2 vs 397.6 +/- 52.3
      mOsm/kg, p < 0.05), higher serum osmolal gap (162.6 +/- 76.7 vs 105.6 +/- 52.9
      mOsm/kg, p < 0.05), lower arterial pH (6.86 +/- 0.08 vs 7.38 +/- 0.16, p < 0.01),
      lower serum bicarbonate (4.6 +/- 1.6 vs 19.9 +/- 5.7 mmol/L, p < 0.01), and
      higher serum anion gap (36.5 +/- 1.3 vs 14.3 +/- 6.7 mEq/L, p < 0.01). Delay in
      the ED until hemodialysis was started did not differ (group A 6.4 +/- 2.6 hr,
      group B 5.3 +/- 3.5 hr), while duration of hemodialysis until serum methanol
      levels became permanently undetectable was longer in group A (15.0 +/- 0.5 vs 8.4
      +/- 4.4 hr, p < 0.01). The ingested dose of methanol and the delay between
      ingestion and initiation of therapy to block methanol metabolism (ethanol
      infusion) and remove methanol from the body (hemodialysis) appear to be the
      critical factors influencing the outcome of methanol intoxication. Early
      diagnosis and initiation of treatment before substantial parts of the ingested
      methanol have been metabolized are of paramount importance in ensuring a
      favorable outcome.

PMID- 28455929
TI  - Comparison of Preventive Care Provided to Dialysis Patients by Nephrologists and
      to Patients Followed in General Medical Clinics: Compliance with American College
      of Physicians Guidelines.
AB  - Most end-stage renal disease (ESRD) patients do not have primary-care providers,
      and preventive medicine often is provided by their nephrologists. Little has been
      written about their success in providing this care. We studied all patients on
      dialysis at our hospital and compared their preventive care to a control group
      followed in the general medical clinic. The general medical group showed higher
      compliance with Pap smears (89% vs 48%), mammography (87% vs 62%), fecal occult
      blood testing (75% vs 50%), and pneumococcal vaccination (55% vs 28%). The ESRD
      group had better compliance with influenza vaccination (70% vs 55%) and lipid
      profile (100% vs 75%). When the subgroup of patients on hemodialysis (HD) was
      compared with patients on peritoneal dialysis (PD), it was shown that HD patients
      were more likely than PD patients to receive preventive care. We also compared
      diabetes-specific care. The ESRD group had a higher rate of HbA 1C (100% vs 78%)
      and lipid monitoring (100% vs 76%), diabetes education (100% vs 84%), and
      podiatry visits (70% vs 38%). There was no difference in ophthalmologic
      examination or influenza vaccination. We found that nephrologists provide
      preventive care to ESRD patients with success approximately equal to primary-care
      physicians in our institution, although in different parameters. Ready access to
      dialysis patients and their blood and unit-specific policies contribute to
      compliance that is above national averages. Further improvements can be made by
      additional preventative measures policies, by physician and patient education,
      and by monitoring primary-care compliance in the chart.

PMID- 28455930
TI  - The Middle Molecule Hypothesis Revisited. Should Short, Three Times Weekly
      Hemodialysis Be Abandoned?
AB  - When the middle molecule (MM) hypothesis was formulated in 1975, no MM had yet
      been identified as a uremic toxin. Meanwhile, the birth and implementation of the
      Kt/Vurea concept gained wide acceptance and has remained the world standard for
      assessing dialysis adequacy. However, over the past 20 years, accumulating
      evidence has made it clear that MM's are important uremic toxins, and that the
      dose of dialysis based on removal of small molecular substances does not protect
      against excessive hemodialysis mortality, morbidity, or the presence of uremic
      signs and symptoms. These poor results are, in one way or another, linked to the
      accumulation of MM's and other substances behaving like MM's, such as phosphate.
      Dialysis schedules yielding the best clinical results, such as longer dialysis
      and more frequent dialysis, favor increased removal of middle molecular
      substances. The observation that short daily dialysis is giving results similar
      to long nocturnal quotidian dialysis supports early observations that the volume
      from which middle molecular substances are extracted mainly by hemodialysis is
      small (about as large as the extracellular volume), and that transfer of MM's
      from cells to extracellular fluid is very slow. This behavior of MM's is markedly
      different from that of small molecular substances, which are more rapidly
      transferred from intracellular to extracellular compartments and are more readily
      extracted from total body water during hemodialysis. In order to achieve even
      minimum adequate dialysis, it is now scientifically validated that toxic MM's
      must be removed in larger amounts than currently attained. This can only be
      accomplished by long dialysis sessions with a 3-times per week schedule or more
      frequent dialyses. Five hours 3 times per week represents the absolute minimum
      treatment. Dialy sis 6 to 7 times per week is the ideal schedule for patients who
      are willing to commit the time and effort in exchange for maximum well-being and
      long survival.

PMID- 28455931
TI  - A Composite Index of Compliance for Chronic In-Center Hemodialysis Patients.
AB  - We developed a composite compliance index as the sum of the compliance scores for
      interdialytic weight gain (IDWG), pre-dialysis serum potassium and phosphorus
      concentrations (each scored from zero to 3, with 3 indicating the poorest
      compliance), and skipping hemodialysis sessions (scored from zero to 9, with 9
      indicating the poorest compliance). We used this composite score to prospectively
      evaluate compliance in 25 prevalent hemodialysis patients over a period of 1
      year. We then followed these patients for another 3.5 years. The patients studied
      were divided into two groups: group A (poor compliance) consisted of 9 subjects
      with composite score >= 9 (13.2 +/- 3.2); group B (better compliance) consisted
      of 16 subjects with composite score < 9 (4.7 +/- 1.8). Age, duration of
      hemodialysis, and frequency of diabetes mellitus did not differ between the
      groups. Group A contained higher fractions of subjects with history of alcoholism
      (66.7% vs 12.5%, p = 0.010), other substance addiction (44.4% vs 0%, p = 0.010),
      and severe psychosocial problems (88.9% vs 18.8%, p = 0.002). Mean survival from
      the beginning of observation, estimated by actuarial life-table survival
      analysis, was 1.19 years in group A and 2.60 years in group B (p = 0.0265). A
      composite compliance index incorporating domains indicating adherence to diet,
      medications, and dialysis schedule identified other behavioral problems in poorly
      compliant patients. Hemodialysis patients characterized by this composite index
      as poorly compliant had shortened survival.

PMID- 28455932
TI  - EKR c Versus stdKt/V: What's the Difference? What's the Meaning?

PMID- 28455933
TI  - Do Catheter Side Holes Provide Better Blood Flows?
AB  - Four catheters (Ash Split Cath, Tesio, Duo-Split, and Duo--Flow; Medcomp,
      Harleysville, PA, U.S.A.) were tested in a temperature-controlled in vitro setup
      filled with 50% aqueous glycerin solution to determine hydraulic resistance at
      different flow rates. All these catheters have side holes; hydraulic resistance
      was determined with these holes open and closed. Due to extra pressure losses
      near the catheter tip, the pressure-flow relationship deviates from Poiseuillian
      theory and is generally quadratic in nature. An equivalent diameter was derived
      from the data. This equivalent diameter can be used to evaluate performance using
      a single number. Permanent catheters can easily deliver 300 mL/minute under
      optimal circumstances, but acute catheters are, in practice, limited to 200
      mL/minute, and even somewhat less in the coaxial Duo-Flow type. Permanent
      catheters have larger equivalent internal diameters (1.8 vs 1.45 mm). Covering
      the side holes does not influence hydraulic resistance to a great degree, except
      in the arterial limb of acute catheters. These results indicate that, especially
      in acute catheters, obstruction of the side holes or fibrin sleeve/thrombus
      formation over the inlet holes may severely impact the available blood flow rate
      during dialysis. On the other hand, side holes in permanent catheters or venous
      limbs seem to be superfluous for performance reasons.

PMID- 28455934
TI  - Phosphorus Clearance Using Two Hemodialyzers Placed in Parallel.
AB  - Control of hyperphosphatemia is a major goal in patients with end-stage renal
      disease. However, removal of retained inorganic phosphorus during hemodialysis
      remains a major problem. We compared clearances and total phosphate removal in
      large patients treated with two F-80 dialyzers (Fresenius Medical Care of North
      America, Lexington, MA, U.S.A.) placed in parallel, and small patients dialyzed
      with a single F-80 dialyzer (SD). Clearances were obtained using total dialysate
      collections. Eight dialysate collections (5 patients) using double parallel
      dialyzers (DD group) were compared with 5 dialysate collections (4 patients)
      using single dialyzers (SD group). Blood and dialysate flow rates and time of
      dialysis treatment were identical between the groups. The DD group's Kt/V urea
      was 1.46 +/- 0.13; SD group's Kt/V urea was 1.35 +/- 0.09 (p = 0.2). Absolute
      phosphorus removal was 1594 +/- 300 mg for the DD group, compared to 1108 +/- 285
      mg in the SD group (p = 0.03). Urea clearance in the DD group was 285 +/- 25
      mL/minute and 251 +/- 27 mL/ min in the SD group (p = 0.082). Phosphorus
      clearance was 178 +/- 32 mL/min in the DD group and 149 +/- 38 mL/min in the SD
      group (p = 0.039). There was no correlation between phosphorus clearance and
      dialyzer reuse. The bulk of phosphorus removal was achieved during the first 2
      hours of hemodialysis. This finding is consistent with the hypothesis that there
      are at least two pools of body phosphorus. Using hemodialyzers placed in parallel
      led to higher phosphate clearance and total phosphorus removal. This higher
      phosphate removal may be related in part to increasing the concentration gradient
      for transfer out of a second compartment.

PMID- 28455935
TI  - Cardioprotection in the ESRD Population: How Do We Get There?
AB  - Cardiovascular mortality for end-stage renal disease (ESRD) patients is about 30
      times the risk in the general population. About 30% of ESRD patients have
      hyperlipidemia. The 1998 National Kidney Foundation Task Force on Cardiovascular
      Disease recommends implementation of effective measures to prevent and treat
      cardiovascular disease in this population. Our intent was to evaluate the extent
      of use of cardioprotective drugs in ESRD patients through a quality improvement
      project. Twenty-eight dialysis facilities throughout Ohio volunteered for this
      project. Data regarding use of angiotensin-converting enzyme inhibitors (ACE-I)
      and angiotensin receptor blockers (ARB) in heart failure, beta-blockers in
      myocardial infarction (MI), aspirin in coronary artery disease, and 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) were collected
      using chart abstraction for the period March through May 2000. The results were
      compared to Ohio hospital discharges from July through September 2000. This
      latter population was comprised of non--ESRD patients. Dialysis facilities were
      visited and interviews were conducted with staff members. Information was
      gathered regarding facility infrastructure, quality improvement process, and
      existing protocols. 27% of ESRD patients with a history of heart failure were on
      ACE-I, compared to 75.7% of non-ESRD patients. 34.8% of ESRD patients with a
      previous MI were taking beta-blockers, compared with 68.0% of non-ESRD patients
      with a prior MI. Aspirin use in ESRD patients with a previous MI was 52.8%,
      compared to 88% in non-ESRD patients with a prior MI. 17.3% of ESRD patients were
      on statins. Hyperlipidemia is found in 30% to 50% of ESRD patients. The use of
      cardioprotective drugs in the Medicare ESRD patient is lower than in the Medicare
      non-dialysis counterpart. Reasons for this are related to fragmentation of health
      care arising from communication and infrastructure issues. Until these issues are
      addressed and resolved, efforts at initiation of cardioprotective strategies will
      be slowed.

PMID- 28455936
TI  - Knowledge of Home Dialysis Among Inner-City Satellite Hemodialysis Patients.
AB  - There is limited use of home renal replacement therapies in the U.S.A. One
      percent of dialysis patients are on home hemodialysis (HHD) and only 9% undergo
      peritoneal dialysis (PD). In an effort to better understand this, 161 satellite
      hemodialysis patients in 6 units in Brooklyn were surveyed. Forty-eight percent
      of patients were women, 86% were black, 5% white, 8% Hispanic, and 1% other. Mean
      age was 49.4 years (range 22 - 69 years). Etiology of renal disease was
      hypertension (41%), diabetes mellitus (31%), polycystic kidney disease (3%),
      systemic lupus erythematosus (4%), and other or unknown (21%). Patients were
      queried about knowledge of and attitudes toward home therapies. Seventy-nine
      percent of patients knew of home dialysis. The source of this information was the
      nephrologist (59%), the social worker (14%), a nurse (8%), other patients (4%),
      and other sources (15%). Only 10% of patients had ever considered HHD. Fifty-four
      percent were afraid to do self-care at home and 35% were not interested.
      Surprisingly, only 3% felt they had no reliable helper and 8% felt that their
      housing was not suitable. Similarly, 78% of patients had been spoken to about PD,
      but only 11% had considered it. Forty-one percent were afraid of doing self-care
      on PD, and 45% were not interested. We conclude that, although the majority of
      patients in six inner-city dialysis units had heard of home dialysis, only a
      small number ever considered it. As many patients were afraid of doing home
      therapy, better education about the risks and benefits needs to be disseminated.

PMID- 28455937
TI  - Pitfalls in the Use of Anticoagulants.
AB  - Anticoagulants are in widespread use for the management of a variety of
      conditions, ranging from thrombus prevention to the treatment of arterial and
      venous occlusion. As with any effective therapy, recognition of adverse effects
      is critically important for the safe use of these drugs. Pitfalls in the use of
      heparins include dosing in close proximity to invasive procedures; not closely
      monitoring patients in whom dose adjustments may be required, such as the very
      obese, the elderly, and patients with renal or hepatic failure; failing to make
      dose adjustments during pregnancy; and not recognizing when patients are
      developing heparin-induced thrombocytopenia or osteoporosis. Pitfalls in the use
      of unfractionated heparin include delays in achieving a therapeutic activated
      partial thromboplastin time (aPTT) and failure to consider the effects of protein
      binding in acutely ill patients. A pitfall in the use of low molecular weight
      heparin is giving prophylactic doses when therapeutic doses are indicated.
      Pitfalls in the use of warfarin are stopping heparin before the warfarin is fully
      effective; failing to maintain the International Normalized Ratio within the
      therapeutic range; failing to adjust the dose of warfarin because of changes in
      diet, renal or hepatic failure, and exposure to new drugs; failing to stop
      warfarin at an appropriate interval before an invasive procedure; and giving
      warfarin during pregnancy. Pitfalls in the use of thrombin inhibitors include
      using them with thrombolytic agents; giving them in proximity to invasive
      procedures; not adjusting the dose for renal or hepatic failure; and failing to
      consider the effect of these agents on the prothrombin time when initiating
      warfarin therapy.

PMID- 28455938
TI  - Comparison of Staff-Assisted Home Hemodialysis with In-Center Hemodialysis and In
      Hospital Hemodialysis.
AB  - Home hemodialysis (HHD) is superior to in-center hemodialysis (ICHD) in terms of
      survival, quality of life, and cost-effectiveness. However, assistance from
      family members in performing HHD is not always available to patients, and
      professional assistance for HHD can be cost prohibitive. For certain patients,
      ICHD can be impractical due to difficulties in transportation, which may
      necessitate ambulance transportation or hospitalization for in-hospital
      hemodialysis (IHHD). We describe 4 patients that have had problems receiving ICHD
      for various reasons. Two of these patients had problems with transportation,
      while the other two could not remain on dialysis for the prescribed duration of
      time and, therefore, received inadequate dialysis. These patients had difficulty
      while receiving ICHD in meeting the adequacy criteria set by Dialysis Outcomes
      Quality Initiative. One of these patients had a neuropsychiatric disorder and
      displayed disruptive behavior. When these 4 patients were switched to staff
      assisted home hemodialysis (SAHD), the dialysis core indicators improved compared
      with ICHD, and the patients needed significantly fewer hospitalization days. In
      this paper, we demonstrate that, in patients that cannot be easily transferred,
      and in patients with neuropsychiatric disorders, SAHD can be a less expensive and
      more efficacious modality of dialysis.

PMID- 28455939
TI  - 2003 Hemodialysis Symposium to Be Held in Seattle.

PMID- 28455940
TI  - Unleashing the Potential of 17 O NMR Spectroscopy Using Mechanochemistry.
AB  - 17 O NMR spectroscopy has been the subject of vivid interest in recent years,
      because there is increasing evidence that it can provide unique insight into the
      structure and reactivity of many molecules and materials. However, due to the
      very poor natural abundance of oxygen-17, 17 O labeling is generally a
      prerequisite. This is a real obstacle for most research groups, because of the
      high costs and/or strong experimental constraints of the most frequently used 17
      O-labeling schemes. Here, we show for the first time that mechanosynthesis offers
      unique opportunities for enriching in 17 O a variety of organic and inorganic
      precursors of synthetic interest. The protocols are fast, user-friendly, and low
      cost, which makes them highly attractive for a broad research community, and
      their suitability for 17 O solid-state NMR applications is demonstrated.

PMID- 28455941
TI  - Molecularly Imprinted Nanogels Acquire Stealth In Situ by Cloaking Themselves
      with Native Dysopsonic Proteins.
AB  - Protein corona formation was regulated on the surface in vivo by molecular
      imprinting to enable polymeric nanogels to acquire stealth upon intravenous
      administration. Albumin, the most abundant protein in blood, was selected as a
      distinct protein component of protein corona for preparing molecularly imprinted
      nanogels (MIP-NGs) to form an albumin-rich protein corona. Intravital
      fluorescence resonance energy transfer imaging of rhodamine-labeled albumin and
      fluorescein-conjugated MIP-NGs showed that albumin was captured by MIP-NGs
      immediately after injection, forming an albumin-rich protein corona. MIP-NGs
      circulated in the blood longer than those of non-albumin-imprinted nanogels, with
      almost no retention in liver tissue. MIP-NGs also passively accumulated in tumor
      tissue. These data suggest that this strategy, based on regulation of the protein
      corona in vivo, may significantly influence the development of drug nanocarriers
      for cancer therapy.

PMID- 28455942
TI  - The evaluation of pelvic floor muscle strength in women with pelvic floor
      dysfunction: A reliability and correlation study.
AB  - AIMS: The purposes of this study were: (i) to evaluate the reliability of vaginal
      palpation, vaginal manometry, vaginal dynamometry; and surface (transperineal)
      electromyography (sEMG), when evaluating pelvic floor muscle (PFM) strength
      and/or activation; and (ii) to determine the associations among PFM strength
      measured using these assessments. METHODS: One hundred and fifty women with
      pelvic floor disorders participated on one occasion, and 20 women returned for
      the same investigations by two different raters on 3 different days. At each
      session, PFM strength was assessed using palpation (both the modified Oxford
      Grading Scale and the Levator ani testing), manometry, and dynamometry; and PFM
      activation was assessed using sEMG. RESULTS: The interrater reliability of
      manometry, dynamometry, and sEMG (both root-mean-square [RMS] and integral
      average) was high (Lin's Concordance Correlation Coefficient [CCC] = 0.95, 0.93,
      0.91, 0.86, respectively), whereas the interrater reliability of both palpation
      grading scales was low (Cohen's Kappa [k] = 0.27-0.38). The intrarater
      reliability of manometry (CCC = 0.96), and dynamometry (CCC = 0.96) were high,
      whereas intrarater reliability of both palpation scales (k = 0.78 for both), and
      of sEMG (CCC = 0.79 vs 0.80 for RMS vs integral average) was moderate. The Bland
      Altman plot showed good inter and intrarater agreement, with little random
      variability for all instruments. The correlations among palpation, manometry, and
      dynamometry were moderate (coefficient of determination [r2 ] ranged from 0.52 to
      0.75), however, transperineal sEMG amplitude was only weakly correlated with all
      measures of strength (r2  = 0.23-0.30). CONCLUSIONS: Manometry and dynamometry
      are more reliable tools than vaginal palpation for the assessment of PFM strength
      in women with pelvic floor disorders, especially when different raters are
      involved. The different PFM strength measures used clinically are moderately
      correlated; whereas, PFM activation recorded using transperineal sEMG is only
      weakly correlated with PFM strength. Results from perineal sEMG should not be
      interpreted in the context of reporting PFM strength.

PMID- 28455943
TI  - Achilles tendon adaptation in cross-country runners across a competitive season.
AB  - Ultrasound tissue characterization (UTC) is an imaging tool used to quantify
      tendon structural integrity. UTC has quantified Achilles tendon (AT) acute
      response to load in athletes; however, AT response to cumulative load over a
      season is unknown. The purpose of this study was to evaluate AT response across a
      four-month competitive season in collegiate cross-country (XC) runners.
      Participants (n=21; male=9, female=12; age=19.8+/-1.2 years; height=171.9+/-8.9
      cm; weight=60.2+/-8.5 kg) were imaged using the UTC device with a 10-MHz linear
      array transducer mounted in a tracking device. The device captures images at 0.2
      mm intervals along the AT. UTC algorithms quantified the stability of pixel
      brightness over every 17 contiguous transverse images into four echo types (I
      IV). A total of 168 scans (n=21, bilateral limbs) were performed monthly across
      the four-month season (Aug=M1, Sep=M2, Oct=M3, Nov=M4). Echo-type percentages (%)
      were calculated from each scan. Generalized estimating equations (GEE) linear
      regression models evaluated echo-type % change (beta) over the season
      (M1=reference). Type I increased from M1 to M4 (beta=9.10, P<.01; 95%CI: 7.01,
      11.21) and Type II decreased from M1 to M3 (beta=-2.71, P=.018; 95%CI: -4.96, 
      0.47) and M1 to M4 (beta=-10.19, P<.01; 95%CI: -12.22, -8.17). Type III increased
      from M1 to M3 (beta=0.42, P=.003; 95%CI: 0.19, 0.65) and M1 to M4 (beta=0.49,
      P=.002; 95%CI: 0.18, 0.81), Type IV increased from M1 to M4 (beta=0.57, P<.01;
      95%CI: 0.29, 0.84). A positive adaptation in AT structural integrity was observed
      over the XC season, with a ~10% shift from Type II to Type I UTC echo types,
      suggesting AT resilience to a competitive season of repetitive loading in highly
      trained runners.

PMID- 28455944
TI  - Patterns of medical management of overactive bladder (OAB) and benign prostatic
      hyperplasia (BPH) in the United States.
AB  - AIMS: Overactive bladder (OAB) and benign prostatic hyperplasia (BPH) are highly
      prevalent conditions that place a large burden on the United States (US) health
      care system. We sought to analyze patterns of prescription medication usage for
      incident OAB in men and women, and for incident BPH in men using US health
      insurance claims data. MATERIALS AND METHODS: This study used Truven Health
      MarketScan(r) Commercial and Medicare Supplemental Research databases. The data
      were pooled from diverse points of care. BPH subjects included men age 18+ with
      the first and last two diagnoses of BPH >=30 days apart and no BPH diagnosis for
      1 year prior. OAB subjects included men and women age 18+, who were diagnosed
      similarly with incident OAB. The type of medication, medication continuation
      (persistence), and switching to a different medication were analyzed through
      September 30, 2013. RESULTS: Medication persistence was much higher overall for
      BPH than OAB (56% vs 34%, respectively, P < 0.0001), and was highest among men
      with BPH age 65+ (62%). Patients age 18-64 were less likely to continue
      medication than older adults (age 65+) for both BPH and OAB. A 9.4% of patients
      in the OAB cohort and 6.9% of men with BPH switched from one medication to
      another. CONCLUSIONS: Persistence was higher with BPH than OAB medications
      overall, whereas switching rates were higher in the OAB group. The lower
      persistence of OAB medication may be due to less efficacy or tolerability. The
      possibility of under treatment of OAB also warrants future investigations.

PMID- 28455945
TI  - The influence of delipidation on triglyceride and LIPIN1 of porcine embryos
      derived from parthenogenetic activation.
AB  - Proteins in the LIPIN family play key roles in lipid synthesis mainly on
      triacylglycerol (TAG) biosynthesis, and they also act as transcriptional
      coactivators to regulate the expression of genes involved in lipid metabolism
      with other nuclear factors. Hence, this study was designed to investigate LIPIN1
      in pig oocytes and embryos by the delipidation. After delipidation, the content
      of lipids (LDs) and TAG in MII oocyte was significantly reduced; however, a
      similar increasing tendency of TAG was shown during embryos development.
      Subsequently, the expression of genes related to TAG biosynthesis including
      GPAT1, AGPAT1, AGPAT2, LIPIN1, DGAT and the nuclear factors interacted with
      LIPIN1 including PPARalpha and PPARgamma was investigated. It is obvious that
      DGAT and GPAT1, and LIPIN1 increased significantly after delipidation at 1-cell
      and 4-cell stage, and the expression of PPARalpha and PPARgamma also increased at
      4-cell stage. By immunofluorescence staining and Western blots, LIPIN1 was found
      to exhibit a dynamic localization pattern and gradually increase with the
      development of delipated embryo. In the early developmental stages (1-, 2- and 4
      cell stages), it was distributed over the cortical layer. But at the blastocyst
      stage, a homogeneous distribution of LIPIN1 was observed in cytoplasm. At 2-cell
      stage, the expression of PPARalpha decreased when LIPIN1 was interfered by small
      interfering RNA, but PPARgamma has no significant difference. Therefore, in this
      study, we find after delipidation, the content of TAG and LIPIN1 will gradually
      increase during embryo development and nuclear factor PPARalpha and PPARgamma can
      also be affected by delipidation. The interaction of LIPIN1 and PPARalpha exists
      in porcine embryo.

PMID- 28455946
TI  - Response to "Pharmacogenetics of Voriconazole: CYP2C19 but Also CYP3A4 Need to Be
      Genotyped" - The Role of CYP3A4 and CYP3A5 Polymorphisms in Clinical
      Pharmacokinetics of Voriconazole.

PMID- 28455947
TI  - Extended day length in late winter/early spring, with a return to natural day
      length of shorter duration, increased plasma testosterone and sexual performance
      in rams with or without melatonin implants.
AB  - Sixteen rams were used to quantify the effects of long days, imposed during late
      winter/early spring, with or without exogenous melatonin, on plasma testosterone
      concentrations and ram serving capacity. Rams were assigned to two groups:
      photoperiod-treated rams (Artificial Photoperiod, AP; n = 8), exposed to 2 months
      of long days (16 hr of light/day) between 22 December and 22 February, and
      control rams (Natural Photoperiod, NP; n = 8). At the end of the long-day period,
      AP rams were returned to the natural photoperiod, and each ram in the two groups
      either did (+M) or did not (-M) receive three subcutaneous melatonin implants.
      Four groups were created as follows: AP+M (n = 4), AP-M (n = 4), NP+M (n = 4) and
      NP-M (n = 4). Thirty days after of the onset of photoperiodic treatment, AP rams
      (13.5 +/- 2.8 ng/ml) had significantly (p < .05) lower testosterone levels than
      NP rams (36.7 +/- 1.0), and similar differences were not apparent at the end of
      the photoperiod treatment. A month later, AP rams (24.3 +/- 7.9) had higher (p <
      .10) testosterone levels than NP rams (13.1 +/- 5.0), with no effect of melatonin
      treatment. Fifty days after melatonin implantations, rams were exposed for 20 min
      to three oestrous ewes. AP rams (2.50 +/- 0.42) exhibited significantly (p < .05)
      more serves than did NP rams (1.11 +/- 0.39), and melatonin treatment had no
      significant effect; however, the interaction between treatments was significant.
      Time to first serve was significantly (p < .05) shorter in AP (2.30 +/- 1.20 min)
      than it was in NP rams (5.58 +/- 0.68 min). In conclusion, exposure to 2 months
      of long days in late winter/early spring, with a return to natural day length of
      shorter duration, increased plasma testosterone concentrations and sexual
      performance in rams with or without exogenous melatonin. This particular
      management is an option if a non-hormonal reproductive strategy is scheduled;
      yet, if the use of exogenous hormones is feasible, melatonin implants increase
      the mating efficiency of rams.

PMID- 28455948
TI  - Mobile phone text messaging to improve medication adherence in secondary
      prevention of cardiovascular disease.
AB  - BACKGROUND: Worldwide at least 100 million people are thought to have prevalent
      cardiovascular disease (CVD). This population has a five times greater chance of
      suffering a recurrent cardiovascular event than people without known CVD.
      Secondary CVD prevention is defined as action aimed to reduce the probability of
      recurrence of such events. Drug interventions have been shown to be cost
      effective in reducing this risk and are recommended in international guidelines.
      However, adherence to recommended treatments remains sub-optimal. In order to
      influence non-adherence, there is a need to develop scalable and cost-effective
      behaviour-change interventions. OBJECTIVES: To assess the effects of mobile phone
      text messaging in patients with established arterial occlusive events on
      adherence to treatment, fatal and non-fatal cardiovascular events, and adverse
      effects. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Conference
      Proceedings Citation Index - Science on Web of Science on 7 November 2016, and
      two clinical trial registers on 12 November 2016. We contacted authors of
      included studies for missing information and searched reference lists of relevant
      papers. We applied no language or date restrictions. SELECTION CRITERIA: We
      included randomised trials with at least 50% of the participants with established
      arterial occlusive events. We included trials investigating interventions using
      short message service (SMS) or multimedia messaging service (MMS) with the aim to
      improve adherence to medication for the secondary prevention of cardiovascular
      events. Eligible comparators were no intervention or other modes of
      communication. DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures expected by Cochrane. In addition, we attempted to contact all authors
      on how the SMS were developed. MAIN RESULTS: We included seven trials (reported
      in 13 reports) with 1310 participants randomised. Follow-up ranged from one month
      to 12 months. Due to heterogeneity in the methods, population and outcome
      measures, we were unable to conduct meta-analysis on these studies. All seven
      studies reported on adherence, but using different methods and scales. Six out of
      seven trials showed a beneficial effect of mobile phone text messaging for
      medication adherence. Dale 2015a, reported significantly greater medication
      adherence score in the intervention group (Mean Difference (MD) 0.58, 95%
      confidence interval (CI) 0.19 to 0.97; 123 participants randomised) at six
      months. Khonsari 2015 reported less adherence in the control group (Relative Risk
      (RR) 4.09, 95% CI 1.82 to 9.18; 62 participants randomised) at eight weeks.
      Pandey 2014 (34 participants randomised) assessed medication adherence through
      self-reported logs with 90% adherence in the intervention group compared to 70%
      in the control group at 12 months. Park 2014a (90 participants randomised)
      reported a greater increase of the medication adherence score in the control
      group, but also measured adherence with an event monitoring system for a number
      of medications with adherence levels ranging from 84.1% adherence to 86.2% in the
      intervention group and 79.7% to 85.7% in the control group at 30 days. Quilici
      2013, reported reduced odds of non-adherence in the intervention group (Odds
      Ratio (OR) 0.43, 95% CI 0.22 to 0.86, 521 participants randomised) at 30 days.
      Fang 2016, reported that participants given SMS alone had reduced odds of being
      non-adherent compared to telephone reminders (OR 0.40 95% CI 0.18 to 0.63; 280
      patients randomised). Kamal 2015 reported higher levels of adherence in the
      intervention arm (adjusted MD 0.54, 95% CI 0.22 to 0.85; 200 participants
      randomised). Khonsari 2015 was the only study to report fatal cardiovascular
      events and only reported two events, both in the control arm. No study reported
      on the other primary outcomes. No study reported repetitive thumb injury or road
      traffic crashes or other adverse events that were related to the
      intervention.Four authors replied to our questionnaire on SMS development. No
      study reported examining causes of non-adherence or provided SMS tailored to
      individual patient characteristics.The included studies were small, heterogeneous
      and included participants recruited directly after acute events. All studies were
      assessed as having high risk of bias across at least one domain. Most of the
      studies came from high-income countries, with two studies conducted in an upper
      middle-income country (China, Malaysia), and one study from a lower middle-income
      country (Pakistan). The quality of the evidence was found to be very low. There
      was no obvious conflicts of interest from authors, although only two declared
      their funding. AUTHORS' CONCLUSIONS: While the results of this systematic review
      are promising, there is insufficient evidence to draw conclusions on the
      effectiveness of text message-based interventions for adherence to medications
      for secondary prevention of CVD. Sufficiently powered, high-quality randomised
      trials are needed, particularly in low- and middle-income countries.

PMID- 28455949
TI  - Detection of intracellular reactive oxygen species (superoxide anion and hydrogen
      peroxide) and lipid peroxidation during cryopreservation of alpaca spermatozoa.
AB  - The objective of this study was to detect changes in intracellular reactive
      oxygen species (superoxide anion and hydrogen peroxide) production and lipid
      peroxidation during cryopreservation of alpaca spermatozoa. Twelve alpaca semen
      samples were conventionally cryopreserved. Intracellular superoxide anion and
      hydrogen peroxide were evaluated by fluorescence microscopy using dihydroethidium
      (DHE)/YO-PRO-1 and dichlorofluorescein diacetate (H2DCFDA)/propidium iodide (PI),
      respectively. Evaluations were performed during cooling curve at (1) 25 degrees
      C, (2) 15 degrees C, (3) 5 degrees C/0 min, (4) 5 degrees C/15 min, (5) 5 degrees
      C/30 min and (6) after freezing/thawing. Evaluation of lipid peroxidation by
      measuring malondialdehyde (MDA) was performed at 25 degrees C, 5 degrees C/30 min
      and after thawing. Maximum percentages of total spermatozoa producing superoxide
      anion and hydrogen peroxide were found at 5 degrees C/30 min (62.8 +/- 6.3% and
      30.5 +/- 5.6%, respectively), and these results were higher (p < .05) than
      initial (25 degrees C: 10.8 +/- 3.8% and 6.8 +/- 0.7%, respectively) and after
      thawing (29.8 +/- 9.5% and 7.5 +/- 1.8%, respectively) values. However,
      considering only viable spermatozoa, production of superoxide anion and hydrogen
      peroxide during overall stabilization at 5 degrees C (>76% and >91%,
      respectively) and after thawing (74.9 +/- 5.0% and 78.9 +/- 2.2%, respectively)
      was higher (p < .05) than initial values at 25 degrees C (38.7 +/- 3.1% and 53.6
      +/- 2.0%, respectively). Lipid peroxidation at 25 degrees C, 5 degrees C/30 min,
      and post-thawing were 346.5 +/- 99.8, 401.1 +/- 64.8 and 527.7 +/- 142.8 ng/ml
      MDA, respectively. These results showed that high percentage of viable alpaca
      spermatozoa produces intracellular reactive species oxygen (ROS) during the
      cryopreservation process of alpaca semen.

PMID- 28455950
TI  - Rhadinoviral interferon regulatory factor homologues.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV8) is
      a gammaherpesvirus and the etiological agent of Kaposi's sarcoma, primary
      effusion lymphoma and multicentric Castleman disease. The KSHV genome contains
      genes for a unique group of proteins with homology to cellular interferon
      regulatory factors, termed viral interferon regulatory factors (vIRFs). This
      review will give an overview over the oncogenic, antiapoptotic and
      immunomodulatory characteristics of KSHV and related vIRFs.

PMID- 28455951
TI  - Chronic viral hepatitis and its association with liver cancer.
AB  - Chronic infection with hepatitis viruses represents the major causative factor
      for end-stage liver diseases, including liver cirrhosis and primary liver cancer
      (hepatocellular carcinoma, HCC). In this review, we highlight the current
      understanding of the molecular mechanisms that drive the hepatocarcinogenesis
      associated with chronic hepatitis virus infections. While chronic inflammation
      (associated with a persistent, but impaired anti-viral immune response) plays a
      major role in HCC initiation and progression, hepatitis viruses can also directly
      drive liver cancer. The mechanisms by which hepatitis viruses induce HCC include:
      hepatitis B virus DNA integration into the host cell genome; metabolic
      reprogramming by virus infection; induction of the cellular stress response
      pathway by viral gene products; and interference with tumour suppressors.
      Finally, we summarise the limitations of hepatitis virus-associated HCC model
      systems and the development of new techniques to circumvent these shortcomings.

PMID- 28455952
TI  - Risk of preterm birth by maternal age at first and second pregnancy and
      race/ethnicity.
AB  - We examined the risk of preterm birth (PTB, <37 weeks' gestation) in a second
      pregnancy and analyzed the extent to which this risk varies by maternal age and
      race/ethnicity. The sample included nulligravida mothers in California who
      delivered two singletons between 2005 and 2011. Logistic regression was used to
      calculate the odds of PTB in the second pregnancy. Within each race/ethnicity
      stratum, women delivering term infants in their first pregnancy and between 25
      and 34 years old for both pregnancies served as the referent group. There were
      2,90,834 women included in the study. Among women who delivered their first
      infant at term, the odds of delivering their second infant early differed by race
      and age. Hispanic, Black and Asian non-Hispanic women who were <18 years for both
      pregnancies were at higher odds of having a PTB in their second pregnancy
      (adjusted odds ratios 1.7, 3.3 and 2.9, respectively). Asian non-Hispanic women
      who were <18 years for their first delivery at term and between 18 and 24 years
      for their second delivery, or were >34 years for both, were also at higher odds
      of delivering their second baby prematurely (adjusted odds ratios 1.9 and 1.3,
      respectively). Women who deliver their first infant at <37 weeks of gestation are
      at 3 to 7 times higher odds of delivering their second infant preterm. Providers
      should consider including information about these risks in counseling their
      patients.

PMID- 28455953
TI  - Biotechnology for bioenergy dedicated trees: meeting future energy demands.
AB  - With the increase in human demands for energy, purpose-grown woody crops could be
      part of the global renewable energy solution, especially in geographical regions
      where plantation forestry is feasible and economically important. In addition,
      efficient utilization of woody feedstocks would engage in mitigating greenhouse
      gas emissions, decreasing the challenge of food and energy security, and
      resolving the conflict between land use for food or biofuel production. This
      review compiles existing knowledge on biotechnological and genomics-aided
      improvements of biomass performance of purpose-grown poplar, willow, eucalyptus
      and pine species, and their relative hybrids, for efficient and sustainable
      bioenergy applications. This includes advancements in tree in vitro regeneration,
      and stable expression or modification of selected genes encoding desirable
      traits, which enhanced growth and yield, wood properties, site adaptability, and
      biotic and abiotic stress tolerance. Genetic modifications used to alter
      lignin/cellulose/hemicelluloses ratio and lignin composition, towards effective
      lignocellulosic feedstock conversion into cellulosic ethanol, are also examined.
      Biotech-trees still need to pass challengeable regulatory authorities' processes,
      including biosafety and risk assessment analyses prior to their commercialization
      release. Hence, strategies developed to contain transgenes, or to mitigate
      potential transgene flow risks, are discussed.

PMID- 28455955
TI  - Sphingosine kinase 2 and multiple myeloma.

PMID- 28455954
TI  - Galectin-1 expression imprints a neurovascular phenotype in proliferative
      retinopathies and delineates responses to anti-VEGF.
AB  - Neovascular retinopathies are leading causes of irreversible blindness. Although
      vascular endothelial growth factor (VEGF) inhibitors have been established as the
      mainstay of current treatment, clinical management of these diseases is still
      limited. As retinal impairment involves abnormal neovascularization and neuronal
      degeneration, we evaluated here the involvement of galectin-1 in vascular and non
      vascular alterations associated with retinopathies, using the oxygen-induced
      retinopathy (OIR) model. Postnatal day 17 OIR mouse retinas showed the highest
      neovascular profile and exhibited neuro-glial injury as well as retinal
      functional loss, which persisted until P26 OIR. Concomitant to VEGF up
      regulation, galectin-1 was highly expressed in P17 OIR retinas and it was mainly
      localized in neovascular tufts. In addition, OIR induced remodelling of cell
      surface glycophenotype leading to exposure of galectin-1-specific glycan
      epitopes. Whereas VEGF returned to baseline levels at P26, increased galectin-1
      expression persisted until this time period. Remarkably, although anti-VEGF
      treatment in P17 OIR improved retinal vascularization, neither galectin-1
      expression nor non-vascular and functional alterations were attenuated. However,
      this functional defect was partially prevented in galectin-1-deficient (Lgals1-/
      ) OIR mice, suggesting the importance of targeting both VEGF and galectin-1 as
      non-redundant independent pathways. Supporting the clinical relevance of these
      findings, we found increased levels of galectin-1 in aqueous humor from patients
      with proliferative diabetic retinopathy and neovascular glaucoma. Thus, using an
      OIR model and human samples, we identified a role for galectin-1 accompanying
      vascular and non-vascular retinal alterations in neovascular retinopathies.

PMID- 28455956
TI  - Targeting AXL overcomes resistance to docetaxel therapy in advanced prostate
      cancer.
AB  - Resistance to docetaxel is a major clinical problem in advanced prostate cancer.
      The overexpression of AXL receptor tyrosine kinase (AXL) has been correlated with
      chemotherapeutic drug resistance. However, the role of AXL expression in
      docetaxel resistance in prostate cancer is yet unclear. In this study, we
      demonstrate that AXL is overexpressed and activated independent of Gas6 in
      docetaxel-resistant prostate cancer cells (PC3-DR and DU145-DR). Moreover, we
      show that forced overexpression of AXL in PC3 and DU145 cells is sufficient to
      induce resistance to docetaxel in these cell lines. Notably, genetic or
      pharmacologic inhibition of AXL in the resistant models suppressed cell
      proliferation, migration, invasion, and tumor growth, and these effects were
      significantly augmented when AXL inhibition was combined with docetaxel
      treatment. Mechanistically, we found that AXL inhibition led to reversion of the
      epithelial-mesenchymal transition (EMT) phenotype and decreased the expression of
      ATP-binding cassette B1 (ABCB1). Overall, our results identify AXL as an
      important mediator of docetaxel resistance in prostate cancer. We propose that
      AXL-targeted therapy, in combination with docetaxel, has the potential to improve
      the response to docetaxel therapy and reduce resistance induced by prolonged
      docetaxel therapy in prostate cancer.

PMID- 28455958
TI  - CSFV induced mitochondrial fission and mitophagy to inhibit apoptosis.
AB  - Classical swine fever virus (CSFV), which causes typical clinical characteristics
      in piglets, including hemorrhagic syndrome and immunosuppression, is linked to
      hepatitis C and dengue virus. Oxidative stress and a reduced mitochondrial
      transmembrane potential are disturbed in CSFV-infected cells. The balance of
      mitochondrial dynamics is essential for cellular homeostasis. In this study, we
      offer the first evidence that CSFV induces mitochondrial fission and mitophagy to
      inhibit host cell apoptosis for persistent infection. The formation of
      mitophagosomes and decline in mitochondrial mass relevant to mitophagy were
      detected in CSFV-infected cells. CSFV infection increased the expression and
      mitochondrial translocation of Pink and Parkin. Upon activation of the PINK1 and
      Parkin pathways, Mitofusin 2 (MFN2), a mitochondrial fusion mediator, was
      ubiquitinated and degraded in CSFV-infected cells. Mitophagosomes and
      mitophagolysosomes induced by CSFV were, respectively, observed by the
      colocalization of LC3-associated mitochondria with Parkin or lysosomes. In
      addition, a sensitive dual fluorescence reporter (mito-mRFP-EGFP) was utilized to
      analyze the delivery of mitophagosomes to lysosomes. Mitochondrial fission caused
      by CSFV infection was further determined by mitochondrial fragmentation and Drp1
      translocation into mitochondria using a confocal microscope. The preservation of
      mitochondrial proteins, upregulated apoptotic signals and decline of viral
      replication resulting from the silencing of Drp1 and Parkin in CSFV-infected
      cells suggested that CSFV induced mitochondrial fission and mitophagy to enhance
      cell survival and viral persistence. Our data for mitochondrial fission and
      selective mitophagy in CSFV-infected cells reveal a unique view of the
      pathogenesis of CSFV infection and provide new avenues for the development of
      antiviral strategies.

PMID- 28455959
TI  - OVOL2 antagonizes TGF-beta signaling to regulate epithelial to mesenchymal
      transition during mammary tumor metastasis.
AB  - Great progress has been achieved in the study of the role of TGF-beta signaling
      in triggering epithelial-mesenchymal transition (EMT) in a variety of cancers;
      however, the regulation of TGF-beta signaling during EMT in mammary tumor
      metastasis has not been completely defined. In the present study, we demonstrated
      that OVOL2, a zinc finger transcription factor, inhibits TGF-beta signaling
      induced EMT in mouse and human mammary tumor cells, as well as in mouse tumor
      models. Data from the Oncomine databases indicated a strong negative relationship
      between OVOL2 expression and breast cancer progression. Moreover, our experiments
      revealed that OVOL2 inhibits TGF-beta signaling at multiple levels, including
      inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the
      binding between Smad4 and target DNA, and interfering with complex formation
      between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls
      the TGF-beta signaling output level in vitro and in vivo. The modulation of these
      molecular processes may represent a strategy for inhibiting breast cancer
      invasion by restoring OVOL2 expression.

PMID- 28455960
TI  - A-to-I RNA editing of BLCAP lost the inhibition to STAT3 activation in cervical
      cancer.
AB  - Bladder cancer-associated protein (BLCAP) gene is a highly conserved gene with
      tumor-suppressor function in different carcinomas. It is also a novel ADAR
      mediated editing substrate undergoes multiple A-to-I RNA editing events. Although
      the anti-tumorigenic role of BLCAP has been examined in preliminarily studies,
      the relationship between BLCAP function and A-to-I RNA editing in cervical
      carcinogenesis still require further exploration. Herein, we analyzed the coding
      sequence of BLCAP transcripts in 35 paired cervical cancer samples using high
      throughput sequencing. Of note, editing levels of three novel editing sites were
      statistically different between cancerous and adjacent cervical tissues, and
      editing of these three sites was closely correlated. Moreover, two editing sites
      of BLCAP coding region were mapped-in the key YXXQ motif which can bind to SH2
      domain of STAT3. Further studies revealed that BLCAP interacted with signal
      transducer and activator of transcription 3 (STAT3) and inhibited its
      phosphorylation, while A-to-I RNA editing of BLCAP lost the inhibition to STAT3
      activation in cervical cancer cell lines. Our findings reveal that A-to-I RNA
      editing events alter the genetically coded amino acid in BLCAP YXXQ motif, which
      drive the progression of cervical carcinogenesis through regulating STAT3
      signaling pathway.

PMID- 28455962
TI  - RUNX1 and breast cancer.

PMID- 28455961
TI  - Repositioning chlorpromazine for treating chemoresistant glioma through the
      inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit.
AB  - Patients with glioblastoma have one of the lowest overall survival rates among
      patients with cancer. Standard of care for patients with glioblastoma includes
      temozolomide and radiation therapy, yet 30% of patients do not respond to these
      treatments and nearly all glioblastoma tumors become resistant. Chlorpromazine is
      a United States Food and Drug Administration-approved phenothiazine widely used
      as a psychotropic in clinical practice. Recently, experimental evidence revealed
      the anti-proliferative activity of chlorpromazine against colon and brain tumors.
      Here, we used chemoresistant patient-derived glioma stem cells and chemoresistant
      human glioma cell lines to investigate the effects of chlorpromazine against
      chemoresistant glioma. Chlorpromazine selectively and significantly inhibited
      proliferation in chemoresistant glioma cells and glioma stem cells.
      Mechanistically, chlorpromazine inhibited cytochrome c oxidase (CcO, complex IV)
      activity from chemoresistant but not chemosensitive cells, without affecting
      other mitochondrial complexes. Notably, our previous studies revealed that the
      switch to chemoresistance in glioma cells is accompanied by a switch from the
      expression of CcO subunit 4 isoform 2 (COX4-2) to COX4-1. In this study,
      chlorpromazine induced cell cycle arrest selectively in glioma cells expressing
      COX4-1, and computer-simulated docking studies indicated that chlorpromazine
      binds more tightly to CcO expressing COX4-1 than to CcO expressing COX4-2. In
      orthotopic mouse brain tumor models, chlorpromazine treatment significantly
      increased the median overall survival of mice harboring chemoresistant tumors.
      These data indicate that chlorpromazine selectively inhibits the growth and
      proliferation of chemoresistant glioma cells expressing COX4-1. The feasibility
      of repositioning chlorpromazine for selectively treating chemoresistant glioma
      tumors should be further explored.

PMID- 28455964
TI  - Bispecific protein targets prostate cancer.

PMID- 28455963
TI  - TrkC promotes colorectal cancer growth and metastasis.
AB  - The current work reveals that TrkC receptor is crucial to many aspects of
      tumorigenicity and metastasis of cancer. However, with only a few exceptions,
      such as colorectal cancer (CRC), where suppressing tumorigenic and metastatic
      ability via expression of TrkC as tumor suppressor have been proposed. These
      diverse lines of evidence led us to investigate whether TrkC is involved in CRC
      progression. By using mouse models and molecular biology analyses, we demonstrate
      that TrkC acts as an activator in tumorigenicity and metastasis of colorectal
      cancer. In this study, TrkC was frequently overexpressed in CRC cells, patients'
      tumor samples and an azoxymethane/dextran sulphate sodium-induced mouse model of
      colitis-associated CRCs. TrkC expression was associated with a high-grade CRC
      phenotype, leading to significantly poorer survival. Also, TrkC expression
      promoted the acquisition of motility and invasiveness in CRC. Moreover, TrkC
      increased the ability to form tumor spheroids, a property associated with cancer
      stem cells. Importantly, knockdown of TrkC in malignant mouse or human CRC cells
      inhibited tumor growth and metastasis in a mouse xenograft model. Furthermore,
      TrkC enhanced metastatic potential and induced proliferation by aberrant gain of
      AKT activation and suppression of transforming growth factor (TGF)-beta
      signalling. Interestingly, TrkC not only modulated the actions of TGF-beta type
      II receptor, but also attenuated expression of this receptor. These findings
      reveal an unexpected physiological role of TrkC in the pathogenesis of CRC.
      Therefore, TrkC is a potential target for designing effective therapeutic
      strategies for CRC development.

PMID- 28455965
TI  - Prognosis of stage III colorectal carcinomas with FOLFOX adjuvant chemotherapy
      can be predicted by molecular subtype.
AB  - Individualizing adjuvant chemotherapy is important in patients with advanced
      colorectal cancers (CRCs), and the ability to identify molecular subtypes
      predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could
      be highly beneficial. We performed microarray-based gene expression analysis on
      101 fresh-frozen primary samples from patients with stage III CRCs treated with
      FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC
      samples were classified into four molecular subtypes using nonnegative matrix
      factorization, and for comparison, we also grouped CRC samples using the proposed
      consensus molecular subtypes (CMSs). Of the 101 cases, 80 were classified into a
      CMS group, which shows a 79% correlation between the CMS classification and our
      four molecular subtypes. We found that two of our subtypes showed significantly
      higher disease-free survival and overall survival than the others. Group 2, in
      particular, which showed no disease recurrence or death, was characterized by
      high microsatellite instability (MSI-H, 6/21), abundant mucin production (12/21),
      and right-sided location (12/21); this group strongly correlated with CMS1
      (microsatellite instability immune type). We further identified the molecular
      characteristics of each group and selected 10 potential biomarker genes from
      each. When these were compared to the previously reported molecular classifier
      genes, we found that 31 out of 40 selected genes were matched with those
      previously reported. Our findings indicate that molecular classification can
      reveal specific molecular subtypes correlating with clinicopathologic features of
      CRCs and can have predictive value for the prognosis for stage III CRCs with
      FOLFOX adjuvant chemotherapy.

PMID- 28455967
TI  - Early effective treatment of small pulmonary nodules with video-assisted
      thoracoscopic surgery combined with CT-guided dual-barbed hookwire localization.
AB  - PURPOSE: To assess the feasibility of computed tomography (CT)-guided
      localization using a specific long dual-barbed hookwire in resection of pulmonary
      nodules with the size of 20mm or less by video-assisted thoracoscopic surgery
      (VATS) and to discuss the necessity of early treatment of small pulmonary nodules
      by VATS. RESULTS: All the nodules were successfully localized with hook wire
      under CT guidance. The 34 nodules had a mean diameter of 8.9 +/- 3.8 mm and a
      mean distance from the most superficial edge of the nodules to the visceral
      pleura of 21.4 +/- 12.4 mm. The mean length of time for CT-guided percutaneous
      localization was 9.0 +/- 3.8 minutes. Asymptomatic pneumothorax and parenchyma
      hemorrhage were observed in 1 patient (3.2%) and 5 patients (16.1%),
      respectively. VATS successfully resected all the lesions after localization. The
      mean VATS operation time was 2.6 +/- 1.2 hours (range, 0.8-5.2 hours). 24 (70.6%)
      malignant nodules and 10 benign nodules were discovered after surgery. MATERIALS
      AND METHODS: Between March 2012 and August 2014, 31 patients with 34 small
      pulmonary lesions underwent CT-guided hook wire localization and VATS resection.
      The efficacy of preoperative localization was evaluated in terms of procedure
      time, VATS success rate and associated complications of localization. And the
      pathology and imaging diagnosis of all nodules were recorded. CONCLUSIONS: The CT
      guided Hook-wire localization for pulmonary nodules with the size of 20 mm or
      less is an effective and safe technique to assist VATS. Once small pulmonary
      nodules change in size or number, it is necessary to treat in an early and
      aggressive way with minimally invasive surgery.

PMID- 28455966
TI  - Arginine deiminase expressed in vivo, driven by human telomerase reverse
      transcriptase promoter, displays high hepatoma targeting and oncolytic
      efficiency.
AB  - Arginine starvation has the potential to selectively treat both primary tumor and
      (micro) metastatic tissue with very low side effects. Arginine deiminase (ADI; EC
      3.5.3.6), an arginine-degrading enzyme, has been studied as a potential anti
      tumor drug for the treatment of arginine-auxotrophic tumors. Though ADI-PEG20
      (pegylated ADI by PEG 20,000) already passed the phase I/II clinical trials [1],
      it is just used as adjuvant therapy because of its low efficiency and less
      targeting. Then, this paper discussed the efficiency of arginine starvation
      mediated by ADI expressed in cytoplasm for liver cancers. In order to guarantee
      the tumor targeting, human telomerase reverse transcriptase (hTERT) promoter was
      used to drive the expression of ADI in vivo. To access the anti-tumor efficiency
      of ADI, p53 gene was used as the positive control. Thus, ADI displayed obvious
      cytotoxicity to BEL7402 and HUH7 cell lines in cytoplasm. The apoptosis rates
      rose from 15% to nearly 60% after changing the expression vectors from pcDNA4
      plasmid to adenovirus. Compared with p53-adenovirus, ADI-adenovirus showed the
      higher oncolytic activity in the intratumoral injection model of mice. Tumor
      disappeared after the treatment of ADI-adenovirus for two weeks, and the mice
      pulled through all. Therefore, ADI is an ideal anti-tumor gene for caner
      targeting therapy with the help of hTERT promoter.

PMID- 28455968
TI  - Dishevelled-3 phosphorylation is governed by HIPK2/PP1Calpha/ITCH axis and the
      non-phosphorylated form promotes cancer stemness via LGR5 in hepatocellular
      carcinoma.
AB  - Dishevelled-3 (Dvl3) is regarded as a binding hub with many different interacting
      partners. However, its regulation and mechanism on cancer stemness remain to be
      explored. In this study, we showed that Dvl3 was significantly overexpressed in
      human hepatocellular carcinomas (HCCs) and promoted cancer stemness both in vitro
      and in vivo. We found that the non-phosphorylated (NP)-Dvl3 was more stable than
      the phosphorylated form, more active in activating beta-catenin transcriptional
      activity, and more potent in enhancing self-renewal ability in HCC cells.
      Mechanistically, we confirmed that the homeodomain-interacting protein kinase-2
      (HIPK2) and E3 ubiquitin ligase ITCH were able to physically bind to Dvl3
      protein. Knockdown of HIPK2 and the protein phosphatase regulatory unit C-alpha
      (PP1Calpha) resulted in sustained Dvl3 phosphorylation and hence decrease in the
      NP form of Dvl3. On the other hand, knockdown of E3 ubiquitin ligase ITCH reduced
      the phosphorylation-induced degradation and stabilized the phosphorylated Dvl3
      protein. Furthermore, the NP-Dvl3 enhanced the LGR5 promoter activity to
      upregulate LGR5 expression, which was associated with increased cancer stemness
      in HCC. Our findings established that HIPK2/PP1Calpha/ITCH axis sustains the de
      phosphorylation of Dvl3. This post-translational modification of Dvl3 in turn
      maintains LGR5 expression and enhances the cancer stemness properties in HCC.

PMID- 28455969
TI  - BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via
      mTORC1 pathway.
AB  - Bone morphogenetic protein-2 (BMP2) is a secreted protein that highly expressed
      in a variety of cancers and contributes to cell proliferation, migration,
      invasiveness, mobility, metastasis and EMT. However, its clinical significance
      and biological function in nasopharyngeal carcinoma (NPC) remain unknown up to
      now. Up-regulation of BMP2 was first observed in NPC cell lines by a genome-wide
      transcriptome analysis in our previous study. In this study, BMP2 mRNA was
      detected by qRT-PCR and data showed that it was upregulated in NPC compared with
      non-cancerous nasopharynx samples. Immunohistochemistry (IHC) analysis in NPC
      specimens revealed that high BMP2 expression was significantly associated with
      clinical stage, distant metastasis and shorter survival of NPC patients.
      Moreover, overexpression of BMP2 in NPC cells promoted cell proliferation,
      migration, invasiveness and epithelial-mesenchymal transition (EMT).
      Mechanistically, BMP2 overexpression increase phosphorylated protein level of
      mTOR, S6K and 4EBP1. Correspondingly, mTORC1 inhibitor rapamycin blocked the
      effect of BMP2 on NPC cell proliferation and invasion. In conclusion, our results
      suggest that BMP2 overexpression in NPC enhances proliferation, invasion and EMT
      of tumor cells through the mTORC1 signaling pathway.

PMID- 28455970
TI  - Mitochondrial replacement in an iPSC model of Leber's hereditary optic
      neuropathy.
AB  - Cybrid technology was used to replace Leber hereditary optic neuropathy (LHON)
      causing mitochondrial DNA (mtDNA) mutations from patient-specific fibroblasts
      with wildtype mtDNA, and mutation-free induced pluripotent stem cells (iPSCs)
      were generated subsequently. Retinal ganglion cell (RGC) differentiation
      demonstrates increased cell death in LHON-RGCs and can be rescued in cybrid
      corrected RGCs.

PMID- 28455971
TI  - 2nd interventions in aging conference.

PMID- 28455972
TI  - Metabolism, microbiome and colorectal cancer.

PMID- 28455974
TI  - Strategies for HCC target discovery.

PMID- 28455973
TI  - Markers of arterial health could serve as accurate non-invasive predictors of
      human biological and chronological age.
AB  - The decline in functional capacity is unavoidable consequence of the process of
      aging. While many anti-aging interventions have been proposed, clinical
      investigations into anti-aging medicine are limited by lack of reliable
      techniques for evaluating the rate of ageing. Here we present simple, accurate
      and cost-efficient techniques for estimation of human biological age, Male and
      Female Arterial Indices. We started with developing a model which accurately
      predicts chronological age. Using machine learning, we arrived on a set of four
      predictors, all of which reflect the functioning of the cardiovascular system. In
      Arterial Indices models, results of carotid artery duplex scan that show the
      thickness of the intima media complex and quantitatively describe the degree of
      stenosis are combined with pulse wave velocity and augmentation index
      measurements performed by applanation tonometry. In our cohort, the age of men
      was determined with MAE = 6.91 years (adjusted R-squared = 0.55), and the age of
      women with MAE = 5.87 years (adjusted R2 = 0.69). The Epsilon-accuracies of age
      predicting models were at 86.5% and 80% for women and men, respectively.
      Substantially higher differences between the predicted age and the calendar age
      were noted for patients with Type 2 Diabetes Mellitus (T2D) as compared to non
      T2D controls, indicating that the model could serve as a good approximation for
      an elusive biological age. Notably, in females with chronological and biological
      ages mismatching by 5 or more years, significant increases in in Framingham CVD
      scores and lower levels of IGF-1 were observed. Proposed Male and Female Arterial
      Indices derive biological age from the results of functional tests which do not
      require specialized laboratory equipment and, therefore, could be performed in
      hospitals and community health clinics.

PMID- 28455995
TI  - Boschniakia Rossica Polysaccharide Triggers Laryngeal Carcinoma Cell Apoptosis by
      Regulating Expression of Bcl-2, Caspase-3, and P53.
AB  - BACKGROUND Laryngeal cancer is a malignant head and neck tumor with high
      morbidity and high mortality in humans. Recently, treatments with Chinese
      medicines and their extracts have gradually received great attention, and studies
      suggest that Boschniakia rossica polysaccharide (BRP) has potential anti-tumor
      activity. Therefore, this study investigating the role of BRP in inducing
      apoptosis in human laryngeal carcinoma cells. MATERIAL AND METHODS The BRP was
      extracted with organic solvent and HR column. We treated Hep2 laryngeal carcinoma
      cells with different concentrations of BRP, then assessed cell growth inhibition
      rate by flow cytometry and apoptosis index by TUNEL staining. The protein
      expression of p53, Bcl-2, Bax, and caspase-3 were analyzed by Western blot.
      RESULTS Flow cytometry results showed that BRP inhibited Hep2 cell proliferation
      in a dose-dependent manner (p<0.05), and TUNEL staining indicated that BRP
      significantly increased Hep2 apoptosis index (p<0.05). Western blot results
      showed that the expression levels of p53 and activation of caspase-3 in Hep2
      cells were significantly up-regulated (p<0.05), while the expression of Bcl-2 was
      significantly down-regulated (p<0.05). CONCLUSIONS BRP might induce cell
      apoptosis by regulating the expression level of cell apoptosis-associated
      proteins, suggesting strong anti-laryngeal cancer activity.

PMID- 28455996
TI  - Aliskiren reduces albuminuria after kidney transplantation.
AB  - BACKGROUND: The renoprotective effects of the direct renin inhibitor, aliskiren,
      in renal transplant recipients have been supposed, but not finally proven. We
      performed an exploratory double-blind, losartan controlled, cross-over study to
      evaluate the influence of aliskiren, direct renin inhibitor, on albuminuria and
      other surrogate markers of kidney injury in patients after renal transplantation.
      The safety of this therapy was also evaluated. METHOD: 16 of 18 patients (12 M, 4
      F), 48.3 +/- 9.0 years, 57.7 +/- 9.1 months after kidney transplantation, with
      hypertension and stable serum creatinine 1.4 +/- 0.08 mg/dl without proteinuria,
      completed the protocol. Each patient underwent two 8-week treatment periods (one
      with 150 mg of aliskiren, and one with 50 mg of losartan) in random order,
      allowing an 8-week placebo washout between them. RESULTS: There were no
      differences in albuminuria, transforming growth factor beta-1 and 15-F2t
      isoprostanes urine excretion between aliskiren and losartan. Creatinine serum
      level, eGFR, 24 h systolic and 24 h diastolic blood pressure were stable through
      the study. There were no differences in haemoglobin and potassium serum
      concentration between studied drugs. CONCLUSION: Aliskiren decreases albuminuria
      in renal transplant recipients with clinically minimal side effects. The effect
      does not differ from that of losartan.

PMID- 28455997
TI  - Prognostic value of perioperative assessment of plasma cardiac troponin I in
      patients undergoing liver transplantation.
AB  - : An elevation in plasma cardiac troponins is an indicator of increased
      perioperative risk in orthopaedic and vascular surgery, however, data on liver
      transplantation (LTx) are scarce. The aim of the study was to evaluate the
      prevalence of cardiac troponin I (cTnI) elevation in the perioperative period of
      LTx, and its potential relationship with 1-year mortality. MATERIAL AND METHODS:
      Analysis included 79 patients with liver cirrhosis. During LTx all patients
      underwent hemodynamic measurements. cTnI level was determined before the
      operation, 24, 48 and 72 hours afterwards. One-year mortality was assessed.
      RESULTS: 12.7% patients died, all during in-hospital period. cTnI level on day 1.
      was identified as the most promising marker of increased death risk with optimal
      cut-off value of 0.215 ng/mL (the sensitivity of 60.0%, specificity of 87.0%,
      positive predictive value of 40.0%, negative predictive value of 93.8%). The most
      important predictor of cTnI increase was the duration of the LTx procedure
      followed by amount of packed red blood cells transfused, basic stroke volume
      index, and cardiac output index. IN CONCLUSION: value of cTnI level assessed 24
      hours post-surgery was a reliable predictor of death following LTx with optimal
      cut-off value of 0.215 ng/mL. The surgery time was the most important predictor
      of cTnI elevation.

PMID- 28455998
TI  - New mutations in GJA8 expand the phenotype to include total sclerocornea.
AB  - This project expands the disease spectrum for mutations in GJA8 to include total
      sclerocornea, rudimentary lenses and microphthalmia, in addition to this gene's
      previously known role in isolated congenital cataracts. Ophthalmic findings
      revealed bilateral total sclerocornea in 3 probands, with small abnormal lenses
      in 2 of the cases, and cataracts and microphthalmia in 1 case. Next-generation
      sequencing revealed de novo heterozygous mutations affecting the same codon of
      GJA8 : (c.281G>A; p.(Gly94Glu) and c.280G>C; p.(Gly94Arg)) in 2 of the probands,
      in addition to the c.151G>A; p.(Asp51Asn) mutation we had previously identified
      in the third case. In silico analysis predicted all of the mutations to be
      pathogenic. These cases show that deleterious, heterozygous mutations in GJA8 can
      lead to a severe ocular phenotype of total sclerocornea, abnormal lenses, and/or
      cataracts with or without microphthalmia, broadening the phenotype associated
      with this gene. GJA8 should be included when investigating patients with the
      severe anterior segment abnormality of total sclerocornea.

PMID- 28455999
TI  - Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after
      intravenous and oral administration.
AB  - The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8)
      was investigated. Single doses of posaconazole were administered intravenously
      (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma
      samples collected over 24 and 36 hr, respectively. Plasma concentrations of
      posaconazole were quantified by validated high-performance liquid chromatography.
      A noncompartmental pharmacokinetic analysis of data was performed. Following i.v.
      administration, estimates of the median (range) of plasma clearance (CL) and
      steady-state volume of distribution (Vss ) were 0.15 (0.13-0.18) L hr-1  kg-1 and
      1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life
      (t1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22
      16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median:
      0.66). Following oral administration, maximum plasma concentration (Cmax ;
      median: 0.72, range: 0.55-0.93 MUg/ml) was achieved in 8 (range 6-12) hr. The in
      vitro plasma protein binding of posaconazole incubated at 37 degrees C was 99.25
      +/- 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD)
      targets for some yeasts such as disseminated candidiasis suggests that
      posaconazole could be an efficacious treatment for cryptococcosis in koalas.

PMID- 28456000
TI  - Pharmacokinetics of firocoxib after intravenous administration of multiple
      consecutive doses in neonatal foals.
AB  - The purpose of this study was to determine the pharmacokinetic profile of
      intravenous firocoxib in neonatal foals. Six healthy foals were administered 0.09
      mg/kg firocoxib intravenously once a day for 7 days. Blood was collected for
      plasma firocoxib analysis using high-performance liquid chromatography with
      fluorescence detection at times 0 (day 1 of study only) and 0.08, 0.25, 1, 2, 4,
      6, 8, 16 and 24 hr on dose numbers 1, 5 and 7. Blood was also collected
      immediately prior to doses 3, 4, 5 and 7. Final samples were collected at 36, 48,
      72 and 96 hr following the final dose. Noncompartmental analysis using the
      trapezoidal method with linear interpolation revealed a moderate half-life (15.9
      +/- 9.1 hr) with a large volume of distribution at steady state (1.79 +/- 0.57
      L/kg) and a clearance (96.0 +/- 59.2 ml h-1  kg-1 ) that was more rapid than that
      observed in adult horses.

PMID- 28456001
TI  - High-milking sheep have a lower ovulation rate and tend to yield fewer embryos in
      response to superovulation and intrauterine artificial insemination.
AB  - Antagonistic relationship between milk yield and reproduction is reported in
      several livestock species. This study aimed to investigate whether genetic merit
      for milk production in dairy sheep affects responses to superovulation, embryo
      yield and quality. A total of 21 cross-bred Sarda x Lacaune ewes homogeneous for
      age, parity and stage of lactation were included. The ewes were stratified as
      high-producing or low-producing based on their genetic merit for milk production
      estimated by a pentatrait repeatability animal model. Oestrus was synchronized
      using an intravaginal progesterone pessary inserted on Day 0 and removed on Day
      14. Superovulatory treatment consisted of 350 I.U. of porcine FSH administered in
      eight decreasing intramuscular doses every 12 hr with a total dose of 10 ml of
      solution starting 12 days after insertion of sponges. Laparoscopic artificial
      insemination (AI) was performed 48 hr after pessary removal. Surgical embryo
      recovery was performed at Day 8 after pessary removal. Correlation between
      breeding value for milk production and the number of corpora lutea (CL) was
      significantly different from zero (-0.49). High-producing ewes had a lower number
      of CL than low-producing counterparts (7.6 +/- 2.50 vs 12.1 +/- 5.16
      respectively; p < .02). Furthermore, there was a tendency for high-producing ewes
      to yield fewer embryos than low-producing females (5.3 +/- 3.46 vs 9.18 +/- 5.11;
      p = .09). No differences were observed between ewes in both genetic groups with
      regard to the number of embryos of grades 1, 2 and 3. To our knowledge, this is
      the first report highlighting an antagonism between genetic merit for milk
      production and the ability to produce embryos in sheep. These results deserve to
      be considered in sheep breeding programmes.

PMID- 28456002
TI  - Multiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap
      between neurofibromatosis type 1 and Noonan phenotype.
AB  - Neurofibromatosis type 1 (NF1) has long been considered a well-defined,
      recognizable monogenic disorder, with neurofibromas constituting a pathognomonic
      sign. This dogma has been challenged by recent descriptions of patients with
      enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and
      hypertrophic neuropathy may be a complication of Noonan syndrome with multiple
      lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose
      mother previously received clinical diagnosis of NF1 due to presence of bilateral
      cervical and lumbar spinal lesions resembling plexiform neurofibromas and
      features suggestive of NS. NF1 molecular analysis was negative in the mother. The
      boy presented with Noonan features, multiple lentigines and pectus excavatum.
      Next-generation sequencing analysis of all RASopathy genes identified p.Ser548Arg
      missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal
      magnetic resonance imaging scans were negative in the boy. No heart involvement
      or deafness was observed in proband or mother. This is the first report of a SOS1
      mutation associated with hypertrophic neuropathy resembling plexiform
      neurofibromas, a rare complication in Noonan phenotypes with mutations in
      RASopathy genes. Our results highlight the overlap between RASopathies,
      suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of
      RASopathy genes should be considered when diagnosis is uncertain.

PMID- 28456003
TI  - Sodium-dependent Vitamin C transporter 2 deficiency impairs myelination and
      remyelination after injury: Roles of collagen and demethylation.
AB  - Peripheral nerve myelination involves rapid production of tightly bound lipid
      layers requiring cholesterol biosynthesis and myelin protein expression, but also
      a collagen-containing extracellular matrix providing mechanical stability. In
      previous studies, we showed a function of ascorbic acid in peripheral nerve
      myelination and extracellular matrix formation in adult mice. Here, we sought the
      mechanism of action of ascorbic acid in peripheral nerve myelination using
      different paradigms of myelination in vivo and in vitro. We found impaired
      myelination and reduced collagen expression in Sodium-dependent Vitamin C
      Transporter 2 heterozygous mice (SVCT2+/- ) during peripheral nerve development
      and after peripheral nerve injury. In dorsal root ganglion (DRG) explant
      cultures, hypo-myelination could be rescued by precoating with different collagen
      types. The activity of the ascorbic acid-dependent demethylating Ten-eleven
      translocation (Tet) enzymes was reduced in ascorbic acid deprived and SVCT2+/-
      DRG cultures. Further, in ascorbic acid-deprived DRG cultures, methylation of a
      CpG island in the collagen alpha1 (IV) and alpha2 (IV) bidirectional promoter
      region was increased compared to wild-type and ascorbic acid treated controls.
      Taken together, these results provide further evidence for the function of
      ascorbic acid in myelination and extracellular matrix formation in peripheral
      nerves and suggest a putative molecular mechanism of ascorbic acid function in
      Tet-dependent demethylation of collagen promoters.

PMID- 28456004
TI  - Control of weft yarn or density improves biocompatibility of PET small diameter
      artificial blood vessels.
AB  - Polyethylene glycol terephthalate (PET) fabrics with woven structures have proved
      to be quite effective for use on large diameter artificial blood vessels.
      However, their use within small-diameter artificial blood vessels has been
      associated with poor long-term patency, a problem resulting from slow
      endothelialization on PET and an over hyperplasia of smooth muscle cells.
      Previous research from our laboratory has revealed that ICAM-1 can be used as a
      marker to investigate cell adhesion, an effect which was closely associated with
      cell behavior on the surface of polycaprolactone (PCL) films. Moreover, we found
      that the coarseness or pore size of the surface exerts considerable influence on
      cell adhesion and proliferation on PCL films. In this study, we successfully
      fabricated six types of PET woven fabrics with varying gradients of tightness and
      porosities. Levels of ICAM-1 expression (membrane ICAM-1 & soluble ICAM-1) were
      then determined in these woven fabrics. Our results show that increased levels of
      mICAM-1 and decreased levels of sICAM-1 expression were obtained in HUVECs seeded
      on these six samples. These findings indicate that cell adhesion and
      proliferation on fabric surfaces were strongly influenced by their structural
      parameters, in particular the initial adhesion between the cell and fabric
      surface. In addition, we also found that extracellular matrix adhesion tends to
      prefer flat and tight surfaces, which promotes cell-cell and cell-matrix
      interactions, as well as the endothelialization on the surface of PET fabrics.
      These findings provide some novel insights with regard to the design and
      application of small-diameter artificial blood vessels. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 954-964, 2018.

PMID- 28456005
TI  - A History of Cord Blood Banking and Transplantation.

PMID- 28456006
TI  - Transforming the Approach to Cell-Based Therapies.

PMID- 28456007
TI  - Announcing a New Journal Section: Cord Blood.

PMID- 28456008
TI  - Donor-Dependent and Other Nondefined Factors Have Greater Influence on the
      Hepatic Phenotype Than the Starting Cell Type in Induced Pluripotent Stem Cell
      Derived Hepatocyte-Like Cells.
AB  - Drug-induced liver injury is the greatest cause of post-marketing drug
      withdrawal; therefore, substantial resources are directed toward triaging
      potentially dangerous new compounds at all stages of drug development. One of the
      major factors preventing effective screening of new compounds is the lack of a
      predictive in vitro model of hepatotoxicity. Primary human hepatocytes offer a
      metabolically relevant model for which the molecular initiating events of
      hepatotoxicity can be examined; however, these cells vary greatly between donors
      and dedifferentiate rapidly in culture. Induced pluripotent stem cell (iPSC)
      derived hepatocyte-like cells (HLCs) offer a reproducible, physiologically
      relevant and genotypically normal model cell; however, current differentiation
      protocols produce HLCs with a relatively immature phenotype. During the
      reprogramming of somatic cells, the epigenome undergoes dramatic changes;
      however, this "resetting" is a gradual process, resulting in an altered
      differentiation propensity, skewed toward the lineage of origin, particularly in
      early passage cultures. We, therefore, performed a comparison of human hepatocyte
      and dermal fibroblast-derived iPSCs, assessing the impact of epigenetic memory
      at all stages of HLC differentiation. These results provide the first isogenic
      assessment of the starting cell type in human iPSC-derived HLCs. Despite a trend
      toward improvement in hepatic phenotype in albumin secretion and gene expression,
      few significant differences in hepatic differentiation capacity were found
      between hepatocyte and fibroblast-derived iPSCs. We conclude that the donor and
      inter-clonal differences have a greater influence on the hepatocyte phenotypic
      maturity than the starting cell type. Therefore, it is not necessary to use human
      hepatocytes for generating iPSC-derived HLCs. Stem Cells Translational Medicine
      2017;6:1321-1331.

PMID- 28456009
TI  - Umbilical Cord Blood Transplantation: Challenges and Future Directions.
AB  - Since the first successful allogeneic transplants performed in Seattle 50 years
      ago, the field of transplantation has evolved considerably, with improvements in
      human leukocyte antigen typing, patient selection, reduced intensity regimens,
      and graft-versus-host disease prophylaxis. A major breakthrough has been the
      availability of more donor options, first via the National Marrow Donor Program
      Be the Match [Biol Blood Marrow Transplant 2008;14:2-7]. Then, in the 1990s,
      unrelated umbilical cord blood transplantation became available, first for
      children and then for adults [New Engl J Med 1996;35:157-166]. More recently
      mismatched unrelated transplants and haploidentical donor options became
      available [Blood 2011;118:282-288]. In 2017, there is a donor for almost every
      patient who needs a transplant. In this review, we will discuss the state of the
      science (and art) of cord blood transplant, focusing on successes, challenges,
      and future directions. Stem Cells Translational Medicine 2017;6:1312-1315.

PMID- 28456010
TI  - Substance use and suicide risk in a sample of young Colombian adults: An
      exploration of psychosocial factors.
AB  - BACKGROUND AND OBJECTIVES: Young adults might engage in many risk behaviors,
      including alcohol and drug use, which could lead to mental health problems, such
      as suicide. The aim of this study was to examine specific psychosocial and
      clinical factors that could influence the possible relationship between
      polysubstance use (PSU) and suicide risk in a sample of young Colombian
      participants. METHODS: A sample of 274 young participants (mean age = 21.3 years)
      was evaluated with two substance use screening tests (ASSIST and AUDIT) and five
      scales for clinical and psychosocial factors and suicide risk: The Center for
      Epidemiologic Studies Depression scale, Zung Self-Rating Anxiety scale, Family
      APGAR, the Childhood Trauma Questionnaire, and the Plutchik Suicide Risk scale.
      Correlation and multiple regression analyses were conducted. RESULTS: Use of
      cannabis and tobacco was significantly correlated with suicide risk in the total
      sample (p < .05). Depressive and anxiety symptoms, family functioning, and
      emotional abuse during childhood were significantly associated with suicide risk
      (p < .001), while alcohol use, anxiety symptoms, and family functioning were
      variables significantly related to PSU. DISCUSSION AND CONCLUSIONS: Our findings
      are consistent with previous evidence suggesting a relationship between substance
      use, several psychosocial factors, and suicide risk in young participants.
      SCIENTIFIC SIGNIFICANCE: Our study is one of the first reports the relationship
      between substance use and suicide risk in a Latin American population. (Am J
      Addict 2017;26:388-394).

PMID- 28456012
TI  - Neuregulin-1 positively modulates glial response and improves neurological
      recovery following traumatic spinal cord injury.
AB  - Spinal cord injury (SCI) results in glial activation and neuroinflammation, which
      play pivotal roles in the secondary injury mechanisms with both pro- and
      antiregeneration effects. Presently, little is known about the endogenous
      molecular mechanisms that regulate glial functions in the injured spinal cord. We
      previously reported that the expression of neuregulin-1 (Nrg-1) is acutely and
      chronically declined following traumatic SCI. Here, we investigated the potential
      ramifications of Nrg-1 dysregulation on glial and immune cell reactivity
      following SCI. Using complementary in vitro approaches and a clinically-relevant
      model of severe compressive SCI in rats, we demonstrate that immediate delivery
      of Nrg-1 (500 ng/day) after injury enhances a neuroprotective phenotype in
      inflammatory cells associated with increased interleukin-10 and arginase-1
      expression. We also found a decrease in proinflammatory factors including IL
      1beta, TNF-alpha, matrix metalloproteinases (MMP-2 and 9) and nitric oxide after
      injury. In addition, Nrg-1 modulates astrogliosis and scar formation by reducing
      inhibitory chondroitin sulfate proteoglycans after SCI. Mechanistically, Nrg-1
      effects on activated glia are mediated through ErbB2 tyrosine phosphorylation in
      an ErbB2/3 heterodimer complex. Furthermore, Nrg-1 exerts its effects through
      downregulation of MyD88, a downstream adaptor of Toll-like receptors, and
      increased phosphorylation of Erk1/2 and STAT3. Nrg-1 treatment with the
      therapeutic dosage of 1.5 MUg/day significantly improves tissue preservation and
      functional recovery following SCI. Our findings for the first time provide novel
      insights into the role and mechanisms of Nrg-1 in acute SCI and suggest a
      positive immunomodulatory role for Nrg-1 that can harness the beneficial
      properties of activated glia and inflammatory cells in recovery following SCI.

PMID- 28456013
TI  - The History of Cesarean Birth From 1900 to 2016.
AB  - Nurses struggle with conflicting priorities regarding the care of women during
      childbirth and the expectations of physicians and employers. Nurses are expected
      to perform technologically sophisticated interventions that were once performed
      by physicians, which can affect the perception of comfort that nurses
      traditionally offered. In this historical overview, I suggest that scientific
      childbirth advances have contributed to soaring cesarean rates and identify the
      role of the nurse as a contributor to this trend.

PMID- 28456011
TI  - Neurosteroid biosynthesis down-regulation and changes in GABAA receptor subunit
      composition: a biomarker axis in stress-induced cognitive and emotional
      impairment.
AB  - By rapidly modulating neuronal excitability, neurosteroids regulate physiological
      processes, such as responses to stress and development. Excessive stress affects
      their biosynthesis and causes an imbalance in cognition and emotions. The
      progesterone derivative, allopregnanolone (Allo) enhances extrasynaptic and
      postsynaptic inhibition by directly binding at GABAA receptors, and thus,
      positively and allosterically modulates the function of GABA. Allo levels are
      decreased in stress-induced psychiatric disorders, including depression and post
      traumatic stress disorder (PTSD), and elevating Allo levels may be a valid
      therapeutic approach to counteract behavioural dysfunction. While benzodiazepines
      are inefficient, selective serotonin reuptake inhibitors (SSRIs) represent the
      first choice treatment for depression and PTSD. Their mechanisms to improve
      behaviour in preclinical studies include neurosteroidogenic effects at low non
      serotonergic doses. Unfortunately, half of PTSD and depressed patients are
      resistant to current prescribed 'high' dosage of these drugs that engage
      serotonergic mechanisms. Unveiling novel biomarkers to develop more efficient
      treatment strategies is in high demand. Stress-induced down-regulation of
      neurosteroid biosynthesis and changes in GABAA receptor subunit expression offer
      a putative biomarker axis to develop new PTSD treatments. The advantage of
      stimulating Allo biosynthesis relies on the variety of neurosteroidogenic
      receptors to be targeted, including TSPO and endocannabinoid receptors.
      Furthermore, stress favours a GABAA receptor subunit composition with higher
      sensitivity for Allo. The use of synthetic analogues of Allo is a valuable
      alternative. Pregnenolone or drugs that stimulate its levels increase Allo but
      also sulphated steroids, including pregnanolone sulphate which, by inhibiting
      NMDA tonic neurotransmission, provides neuroprotection and cognitive benefits. In
      this review, we describe current knowledge on the effects of stress on
      neurosteroid biosynthesis and GABAA receptor neurotransmission and summarize
      available pharmacological strategies that by enhancing neurosteroidogenesis are
      relevant for the treatment of SSRI-resistant patients. Linked Articles This
      article is part of a themed section on Pharmacology of Cognition: a Panacea for
      Neuropsychiatric Disease? To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.

PMID- 28456014
TI  - Template-Based Orbital Wall Fracture Treatment Using Statistical Shape Analysis.
AB  - PURPOSE: Aim of this study was to investigate whether a mold generated from a
      statistical shape model of the orbit could be generated to provide a cost
      efficient means for the treatment of orbital fractures. MATERIALS AND METHODS: A
      statistical shape model was created from 131 computed tomographic (CT) scans of
      unaffected adult middle European human orbits. To generate the model, CT scans
      were segmented in Brainlab software, preregistered using anatomic landmarks,
      trimmed to an identical size, and definitely registered. Then, the model was
      created using the global master algorithm. Based on this model, a mold consisting
      of a male part and a female part was constructed and printed using a rapid
      prototyping technique. RESULTS: A statistical shape model of the human orbit was
      generated from 125 CT scans. Six scans (4.5%) presented major anatomic deviations
      and were discarded. A solid mold based on this model was printed. Using this
      mold, flat titanium mesh could be successfully deformed to serve as an orbital
      implant. CONCLUSION: A mold based on the statistical orbital shape could serve as
      a cost-effective means for the treatment of orbital fractures. It allows the
      anatomic preformation of titanium or resorbable implant material for orbital
      reconstruction. Because these materials could be cut from larger sheets, the use
      of a mold would be a cost-effective treatment alternative.

PMID- 28456015
TI  - Do Autotransplanted Teeth Require Elective Root Canal Therapy? A Long-Term Follow
      Up Case Series.
AB  - PURPOSE: To determine the long-term survival and outcomes of 252 autotransplanted
      teeth with a novel root canal therapy (RCT) and follow-up protocol and to
      establish whether elective RCT after autotransplantation is routinely required
      for teeth with complete root formation. PATIENTS AND METHODS: A retrospective
      analysis of 209 patients 10 to 58 years old, with a total of 252 autotransplants
      was carried out with a minimum observational period of 1 year and a maximum
      period of 29 years. Patients were reviewed at specified intervals. Only the teeth
      showing any radiographic or clinical signs of internal resorption (IR), external
      resorption (ER), or pulpal necrosis underwent RCT. A failure was considered the
      loss or extraction of the autotransplanted tooth. RESULTS: Ten of the 252
      autotransplants constituted failures, with 249, 190, 155, 97, 70, and 35 teeth
      surviving at 1, 2, 3, 5, 7, and 10 years, respectively; the remainder were lost
      to follow-up. Eighteen percent of teeth (n = 46) showed radiographic signs of IR,
      ER, and apical pathology (AP). Most cases of ER were observed by 3 years (18 of
      28 teeth) and then at 5 to -8 years. Only 3 teeth showed signs of IR, which were
      observed within 5 years. Most cases of AP were observed within the first year (8
      of 15 teeth) and then at 3 to 6 years. Five teeth showed signs of pulp
      obliteration or sclerosis and did not require RCT, with a maximum period of 16
      years after identification of sclerosis. Retrospective analysis of the data
      showed that 184 autotransplanted teeth had complete root formation and 68 had
      incomplete root formation at the time of autotransplantation. Of the teeth that
      were followed for at least 5 years, 59.3% had complete root formation with no
      signs of pathology and required no RCT. CONCLUSION: Despite the limitation of
      this long-term study of patients lost to follow-up, the results suggest that,
      with close monitoring, some autotransplanted teeth with complete root formation
      that do not undergo RCT could have the potential for revascularization. Hence,
      one could reconsider the protocol of routinely providing RCT after
      autotransplantation. Future long-term studies will be beneficial to assess the
      vascularity of autotransplanted teeth using Doppler flowmetry with a larger
      cohort of patients.

PMID- 28456016
TI  - Building evaluation capacity of local substance abuse prevention programs serving
      LGBQ populations.

PMID- 28456017
TI  - Internship training in computer science: Exploring student satisfaction levels.
AB  - The requirement of employability in the job market prompted universities to
      conduct internship training as part of their study plans. There is a need to
      train students on important academic and professional skills related to the
      workplace with an IT component. This article describes a statistical study that
      measures satisfaction levels among students in the faculty of Information
      Technology and Computer Science in Jordan. The objective of this study is to
      explore factors that influence student satisfaction with regards to enrolling in
      an internship training program. The study was conducted to gather student
      perceptions, opinions, preferences and satisfaction levels related to the
      program. Data were collected via a mixed method survey (surveys and interviews)
      from student-respondents. The survey collects demographic and background
      information from students, including their perception of faculty performance in
      the training poised to prepare them for the job market. Findings from this study
      show that students expect internship training to improve their professional and
      personal skills as well as to increase their workplace-related satisfaction. It
      is concluded that improving the internship training is crucial among the students
      as it is expected to enrich their experiences, knowledge and skills in the
      personal and professional life. It is also expected to increase their level of
      confidence when it comes to exploring their future job opportunities in the
      Jordanian market.

PMID- 28456018
TI  - Unique features in the presentation of insulin epitopes in autoimmune diabetes:
      an update.
AB  - Although an autoimmune disease involves diverse self-antigens, the initiation
      stage may require recognition of a limited number. This concept is verified in
      the non-obese diabetic (NOD) mouse model of autoimmune diabetes, in which strong
      evidence points to insulin as the prime antigen. The NOD mouse bears the I-Ag7
      class II-MHC molecules (MHCII) that share common biochemical features and
      peptidome selection with the human diabetes-susceptible HLA-DQ8. Furthermore,
      both NOD mice and patients with type 1 diabetes (T1D) display an early appearance
      of insulin autoantibodies (IAAs) and subsequent insulin-reactive T cell
      infiltration into the islets. Therefore, a better understanding of insulin
      presentation is crucial for assessing disease pathogenesis and therapeutic
      intervention. Here, we summarize recent advances in insulin presentation events
      that underlie the essential role of this autoantigen in driving autoimmune
      diabetes.

PMID- 28456020
TI  - Deep sequencing of H7N8 avian influenza viruses from surveillance zone supports
      H7N8 high pathogenicity avian influenza was limited to a single outbreak farm in
      Indiana during 2016.
AB  - In mid-January 2016, an outbreak of H7N8 high-pathogenicity avian influenza virus
      (HPAIV) in commercial turkeys occurred in Indiana. Surveillance within the 10km
      control zone identified H7N8 low-pathogenicity avian influenza virus (LPAIV) in
      nine surrounding turkey flocks but no other HPAIV-affected premises. We sequenced
      four of the H7N8 HPAIV isolated from the single farm and nine LPAIV identified
      during control zone surveillance. Evaluation included phylogenetic network
      analysis indicating close relatedness across the HPAIV and LPAIV, and that the
      progenitor H7N8 LPAIV spread among the affected turkey farms in Indiana, followed
      by spontaneous mutation to HPAIV on a single premise through acquisition of three
      basic amino acids at the hemagglutinin cleavage site. Deep sequencing of the
      available viruses failed to identify subpopulations in either the HPAIV or LPAIV
      suggesting mutation to HPAIV likely occurred on a single farm and the HPAIV did
      not spread to epidemiologically linked LPAIV-affected farms.

PMID- 28456019
TI  - Dual host specificity of phage SP6 is facilitated by tailspike rotation.
AB  - Bacteriophage SP6 exhibits dual-host adsorption specificity. The SP6 tailspikes
      are recognized as important in host range determination but the mechanisms
      underlying dual host specificity are unknown. Cryo-electron tomography and sub
      tomogram classification were used to analyze the SP6 virion with a particular
      focus on the interaction of tailspikes with host membranes. The SP6 tail is
      surrounded by six V-shaped structures that interconnect in forming a hand-over
      hand hexameric garland. Each V-shaped structure consists of two trimeric
      tailspike proteins: gp46 and gp47, connected through the adaptor protein gp37.
      SP6 infection of Salmonella enterica serovars Typhimurium and Newport results in
      distinguishable changes in tailspike orientation, providing the first direct
      demonstration how tailspikes can confer dual host adsorption specificity. SP6
      also infects S. Typhimurium strains lacking O antigen; in these infections
      tailspikes have no apparent specific role and the phage tail must therefore
      interact with a distinct host receptor to allow infection.

PMID- 28456021
TI  - PARP1 restricts Epstein Barr Virus lytic reactivation by binding the BZLF1
      promoter.
AB  - The Epstein Barr virus (EBV) genome persists in infected host cells as a
      chromatinized episome and is subject to chromatin-mediated regulation. Binding of
      the host insulator protein CTCF to the EBV genome has an established role in
      maintaining viral latency type, and in other herpesviruses, loss of CTCF binding
      at specific regions correlates with viral reactivation. Here, we demonstrate that
      binding of PARP1, an important cofactor of CTCF, at the BZLF1 lytic switch
      promoter restricts EBV reactivation. Knockdown of PARP1 in the Akata-EBV cell
      line significantly increases viral copy number and lytic protein expression.
      Interestingly, CTCF knockdown has no effect on viral reactivation, and CTCF
      binding across the EBV genome is largely unchanged following reactivation.
      Moreover, EBV reactivation attenuates PARP activity, and Zta expression alone is
      sufficient to decrease PARP activity. Here we demonstrate a restrictive function
      of PARP1 in EBV lytic reactivation.

PMID- 28456023
TI  - Paternal psychopathological risk and psychological functioning in children with
      eating disorders and Disruptive Behavior Disorder.
AB  - Several studies demonstrated that maternal psychopathological risk is related to
      child's maladjustment, but until recently research has relatively neglected
      fathers. Disruptive Behavior Disorder (DBD) and Eating disorders (ED) have a
      large prevalence during childhood but a few studies have focused on their
      association with paternal psychopathological risk. One-hundred and thirty-nine
      children and their fathers were recruited from pediatric hospitals and outpatient
      clinics and paired with a healthy control group (CG). Fathers were administered
      the SCL-90/R and the CBCL 6-18 to assess: 1) psychopathological risk of fathers
      of children with DBD, ED and CG; 2) significant differences between ED and DBD
      fathers' psychopathological profiles; and 3) associations between specific
      fathers' psychopathological symptoms and children's emotional-behavioral
      problems. Fathers of children with ED showed a higher psychopathological risk
      than fathers of DBD offspring. Children with DBD showed higher externalizing
      symptoms. Paternal hostility was associated with internalizing problems in
      children with DBD. Paternal hostility showed a non-significant but clinically
      interesting association with internalizing problems in DBD children;
      interpersonal sensitivity was associated with internalizing problems in ED
      children. This study can constitute a contribution to a better understanding of
      the clinical characteristics of fathers of children with DBD and ED.

PMID- 28456022
TI  - Cellular DEAD-box RNA helicase DDX6 modulates interaction of miR-122 with the 5'
      untranslated region of hepatitis C virus RNA.
AB  - Hepatitis C virus (HCV) subverts the cellular DEAD-box RNA helicase DDX6 to
      promote virus infection. Using polysome gradient analysis and the subgenomic HCV
      Renilla reporter replicon genome, we determined that DDX6 does not affect HCV
      translation. Rather expression of the subgenomic HCV Renilla luciferase reporter
      at late times, as well as labeling of newly synthesized viral RNA with 4
      thiouridine showed that DDX6 modulates replication. Because DDX6 is an effector
      protein of the microRNA pathway, we also investigated its role in miR-122
      directed HCV gene expression. Similar to sequestering miR-122, depletion of DDX6
      modulated HCV RNA stability. Interestingly, miR-122-HCV RNA interaction assays
      with mutant HCV genomes sites and compensatory exogenous miR-122 showed that DDX6
      affects the function of miR-122 at one particular binding site. We propose that
      DDX6 facilitates the miR-122 interaction with HCV 5' UTR, which is necessary for
      stabilizing the viral genome and the switch between translation and replication.

PMID- 28456024
TI  - Accelerometer-measured sedentary behaviour and physical activity of inpatients
      with severe mental illness.
AB  - Sedentary behaviour and lack of physical activity threatens health. Research
      concerning these behaviours of inpatients with severe mental illness is limited
      but urgently needed to reveal prevalence and magnitude. In total, 184 inpatients
      (men n =108, women n =76, mean age 57,4, 20% first generation antipsychotics, 40%
      second generation antipsychotics, 43% antidepressants, mean years hospitalisation
      13 years), with severe mental illness of a Dutch psychiatric hospital wore an
      accelerometer for five days to objectively measure total activity counts per hour
      and percentages in sedentary behaviour, light intensity physical activity and
      moderate to vigorous physical activity. Accelerometer data were compared with
      data of 54 healthy ward employees. Patients showed significantly less activity
      counts per hour compared to employees (p=0.02), although the differences were
      small (d=0.32). Patients were sedentary during 84% of the wear time (50min/h),
      spend 10% in light intensity physical activity and 6% in moderate to vigorous
      physical activity. Age was the only significant predictor, predicting less total
      activity counts/h in higher ages. Decreasing sedentary behaviour and improving
      physical activity in this population should be a high priority in clinical
      practice.

PMID- 28456025
TI  - Relationships among alexithymia, therapeutic alliance, and psychotherapy outcome
      in major depressive disorder.
AB  - Previous studies have found that alexithymia predicts process and outcome of
      psychodynamic psychotherapy across a range of psychiatric disorders. There is
      preliminary evidence that alexithymia may exert its effects on outcome through
      the therapist. Other studies have found that alexithymia does not influence
      outcome of cognitive-behavioral therapy (CBT). The aim of the current study was
      to investigate the capacity of alexithymia to predict therapist- and patient
      rated therapeutic alliance and response to CBT and interpersonal psychotherapy
      (IPT) for major depressive disorder. A total of 75 adults with major depressive
      disorder were randomized to receive weekly sessions of manualized individual CBT
      or IPT for a period of 16 weeks. Pre-treatment alexithymia exhibited a positive
      direct effect on depression change, and a negative indirect effect on depression
      change via patient-rated alliance at week 13. There was no mediating role of
      therapist-rated alliance. Although these findings are preliminary, they suggest
      that pre-treatment alexithymia has meaningful links to psychotherapy process and
      outcome, and that nuanced analyses incorporating intervening variables are
      necessary to elucidate the nature of these links.

PMID- 28456026
TI  - Quality of life in Chinese patients with schizophrenia treated in primary care.
AB  - In China, maintenance treatment for clinically stable patients with schizophrenia
      is usually provided by primary care physicians. This study examined the quality
      of life (QOL) in patients with schizophrenia treated in primary care and explored
      the demographic and clinical characteristics associated with QOL. Altogether, 612
      patients with schizophrenia treated in 22 randomly selected primary care services
      in China formed the study sample. QOL, psychotic and depressive symptoms, extra
      pyramidal symptoms and insight were assessed using standardized instruments. Data
      analyses were conducted with the one sample t-test and multiple linear regression
      analyses. Compared with the normative data for the Chinese general population,
      significantly lower scores in physical and mental QOL domains were found in the
      patient group. Older age, being unemployed, major medical conditions, no smoking,
      more severe depressive and negative symptoms, more frequent insomnia, and
      suicidality were independently associated with poor physical QOL. Male gender,
      more severe depressive and anxiety symptoms, more frequent insomnia, and
      suicidality were independently associated with poor mental QOL. Patients with
      schizophrenia treated in primary care had lower level of QOL in comparison with
      general population. Effective measures need to be implemented to improve their
      QOL.

PMID- 28456027
TI  - Improved sensitivity and specificity of pediatric hospital-acquired venous
      thromboembolism case identification by addition of radiographic and pharmacologic
      elements.

PMID- 28456028
TI  - Bacterial community structure and removal performances in IFAS-MBRs: A pilot
      plant case study.
AB  - The paper reports the results of an experimental campaign carried out on a
      University of Cape Town (UCT) integrated fixed-film activated sludge (IFAS)
      membrane bioreactor (MBR) pilot plant. The pilot plant was analysed in terms of
      chemical oxygen demand (COD) and nutrients removal, kinetic/stoichiometric
      parameters, membrane fouling and sludge dewaterability. Moreover, the cultivable
      bacterial community structure was also analysed. The pilot plant showed excellent
      COD removal efficiency throughout experiments, with average value higher than
      98%, despite the slight variations of the influent wastewater. The achieved
      nitrification efficiency was close to 98% for most of the experiments, suggesting
      that the biofilm in the aerobic compartment might have sustained the complete
      nitrification of the influent ammonia, even for concentrations higher than 100 mg
      L-1. The irreversible resistance due to superficial cake deposition was the
      mechanism that mostly affected the membrane fouling. Moreover, it was noticed an
      increase of the resistance due pore blocking likely due to the increase of the
      EPSBound fraction that could derive by biofilm detachment. The bacterial strains
      isolated from aerobic tank are wastewater bacteria known for exhibiting efficient
      heterotrophic nitrification-aerobic denitrification and producing biofilm.

PMID- 28456029
TI  - Advances in microbe-assisted reclamation of heavy metal contaminated soils over
      the last decade: A review.
AB  - Contamination of agricultural soils with trace metals present lethal consequences
      in terms of diverse ecological and environmental problems that entail entry of
      metal in food chain, soil deterioration, plant growth suppression, yield
      reduction and alteration in microbial community. Metal polluted soils have become
      a major concern for scientists around the globe. Phytoremediation involves the
      hyperaccumulation of metals in different plant parts. Phytoremediation of metals
      from polluted soils could be enhanced through inoculation with metal resistant
      plant growth promoting (PGP) bacteria. These PGP bacteria not only promote plant
      growth but also enhance metal uptake by plants. There are a number of reports in
      the literature where PGP bacterial inoculation improves metal accumulation in
      different plant parts without influencing plant growth. Therefore, there is a
      need to select PGP bacterial strains which possess the potential to improve plant
      growth as well as expedite the phytoremediation of metals. In this review, we
      have discussed the mechanisms possessed by PGP bacteria to promote plant growth
      and phytoremediation of metals. The central part of this review deals with the
      recent advances in microbial assisted-phytoremediation of metals.

PMID- 28456030
TI  - The evaluation of 1,4-benzoquinones as inhibitors of human monoamine oxidase.
AB  - The monoamine oxidase (MAO) enzymes are of considerable pharmacological interest
      and inhibitors are used in the clinic for the treatment of major depressive
      disorder and Parkinson's disease. A limited number of studies have shown that the
      quinone class of compounds possesses MAO inhibition properties. Most notable
      among these is a report that 2,3,6-trimethyl-1,4-naphthoquinone (TMN), present in
      extracts of cured tobacco leafs, is a non-selective inhibitor of both MAO
      isoforms. An older study reports that 1,4-benzoquinone inhibits MAO-A and MAO-B
      from human synaptosomes. Both 1,4-naphthoquinones and 1,4-benzoquinone are
      reported to inhibit the MAOs with a reversible mode of action. Since the MAO
      inhibition properties of additional members of the 1,4-benzoquinone class of
      compounds have not yet been explored, the present study investigates a small
      series of four 1,4-benzoquinones which incorporate phenyl, benzyl, benzyloxy and
      cyclopentyl monosubstitution on C2. The 1,4-benzoquinones were found to be
      moderately potent MAO inhibitors with IC50 values of 5.03-13.2 MUM (MAO-A) and
      3.69-23.2 MUM (MAO-B). These values are comparable to those recorded for 1,4
      benzoquinone of 4.82 MUM (MAO-A) and 10.2 MUM (MAO-B). Of interest however, is
      the finding that the 1,4-benzoquinones are irreversible inhibitors of MAO-A since
      prolonged incubation results in near complete inhibition, and enzyme activity is
      not recovered by dialysis. MAO-B is much less sensitive to inactivation by the
      1,4-benzoquinones. These findings are discussed with reference to a possible
      mechanism by which irreversible inhibition occurs. It may be concluded that
      irreversible 1,4-benzoquinone-derived inhibitors may act as probes for
      investigating quinone reactive sites in the MAOs.

PMID- 28456031
TI  - Identification of thiazolo[5,4-d]pyrimidine derivatives as potent
      antiproliferative agents through the drug repurposing strategy.
AB  - A series of thiazolo[5,4-d]pyrimidine derivatives were synthesized and evaluated
      for their antiproliferative activities on three cancer cell lines. The structure
      activity relationship studies were conducted through the variation in the three
      regions of the thiazolo-pyrimidine core. Substitution with morpholine led to
      compound 24, which exerted the most potent antiproliferative activity as well as
      good selectivity between cancer and normal cells (IC50 values of 1.03 MUM against
      MGC803 and 38.95 MUM against GES-1). In addition, compound 24 inhibited the
      colony formation and migration of MGC803 as well as induced apoptosis. Western
      blot experiments indicated the expression changes of apoptosis-related proteins,
      including up-regulation of Bax and caspase-3/9, as well as down-regulation of Bcl
      2.

PMID- 28456032
TI  - Self-recognition of the racemic ligand in the formation of homochiral dinuclear
      V(V) complex: In vitro anticancer activity, DNA and HSA interaction.
AB  - The reaction of a racemic mixture of Schiff base tridentate ligand with
      vanadium(V) affords homochiral vanadium complex, (VO(R-L))2O and (VO(S-L))2O due
      to ligand "self-recognition" process. The formation of homochiral vanadium
      complex was confirmed by 1H NMR, 13C NMR and X-ray diffraction. The HSA- and DNA
      binding of the resultant complex is assessed by absorption, fluorescence and
      circular dichroism (CD) spectroscopy methods. Based on the results, the HSA- and
      DNA-binding constant, Kb, were found to be 8.0 * 104 and 1.9 * 105 M-1,
      respectively. Interestingly, in vitro cytotoxicity assay revealed the potent
      anticancer activity of this complex on two prevalent cancer cell lines of MCF-7
      (IC50 value of 14 MUM) and HeLa (IC50 value of 36 MUM), with considerably low
      toxicity on normal human fibroblast cells. The maximum cell mortality of 12.3%
      obtained after 48 h incubation of fibroblast cells with 100 MUM of the complex.
      Additionally, the specific DNA- and HSA-binding was also shown using molecular
      docking method. The synthesized complex displayed high potential for biomedical
      applications especially for development of novel and efficient anticancer agents.

PMID- 28456033
TI  - An overview of azoles targeting sterol 14alpha-demethylase for antileishmanial
      therapy.
AB  - The azole antifungal drugs are an important class of chemotherapeutic agents with
      broad-spectrum of activity against yeasts and filamentous fungi, act in the
      ergosterol biosynthetic pathway through inhibition of the cytochrome P450
      dependent enzyme sterol 14alpha-demethylase. Azole antifungals have also been
      repurposed for treatment of tropical protozoan infections including human
      leishmaniasis. Recent advances in molecular biology and computational chemistry
      areas have increased our knowledge about sterol biochemical pathway in Leishmania
      parasites. Based on the importance of sterol biosynthetic pathway in Leishmania
      parasites, we reviewed all studies reported on azoles for potential
      antileishmanial therapy along their structural and biological aspects. This
      review may help medicinal chemists for design of new azole-derived
      antileishmanial drugs.

PMID- 28456034
TI  - Synthesis and cytotoxicity of a novel series of saframycin-ecteinascidin analogs
      containing tetrahydro-beta-carboline moieties.
AB  - A novel bistetrahydrocarboline heptacyclic skeleton and its twenty derivatives
      were prepared from l-tryptophan through a 15-step stereospecific route. The
      cytotoxicities of these compounds were tested against six human cancer cell lines
      including HCT-116, HepG2, BGC-823, MCF-7, A2780, and HT-29. Most of the
      derivatives with amide side chain exhibited the IC50 values at the level of 10-7
      M, and a preliminary structure-activity relationship (SAR) was discussed. Both
      compound 30 with 2-pyridine amide side chain and compound 14 with phthalamide
      side chain showed the most potent and broad cytotoxicity towards all six cell
      lines with the IC50 values at the level of 10-8 M. Molecular docking of compound
      30 indicated it bound to minor groove of DNA duplex.

PMID- 28456035
TI  - Near-UV photooxidation of As(III) by iron species in the presence of fulvic acid.
AB  - Photooxidation of As(III) in ternary As(III) - Fe(III) - Fulvic acid system at pH
      4 was investigated by optical spectroscopy, steady-state photolysis (365 nm) and
      atomic-emission spectrometry with inductively coupled plasma techniques. It was
      found that at all values of [FA]/[Fe] ratio the main photoactive species is OH
      radical formed by photolysis of Fe(III) hydroxocomplexes. Addition of fulvic acid
      leads to mainly negative effect on As(III) photooxidation due to the following
      reasons: (i) slow dark reduction of photoactive Fe(III) species with formation of
      scattering particles and photoinert Fe(II) species; (ii) formation of
      photoreductive Fe(III)-FA complexes incapable to oxidize As(III), (iii)
      competition of both FA and Fe(III)-FA complexes for UVA quanta with FeOH2+
      complex and for OH radicals with As(III). Aging of ternary system is also very
      important parameter leading to one order decrease of quantum yields of both
      Fe(II) formation and As(III) photooxidation.

PMID- 28456036
TI  - Trace element biodistribution in the American alligator (Alligator
      mississippiensis).
AB  - Routine monitoring of contaminant levels in wildlife is important for
      understanding chemical exposure and ultimately the link to ecosystem and human
      health. This is particularly important when the monitored species is
      recreationally hunted for human consumption. In the southeastern United States,
      recreational alligator harvesting takes place annually and in locations that are
      known to be contaminated with environmental pollutants. In this study, we
      investigated the biodistribution of trace elements in the American alligator
      (Alligator mississippiensis) from five sites in Florida, USA. These sites are
      locations where annual recreational alligator harvesting is permitted and two of
      the sites are identified as having high mercury contamination with human
      consumption advisories in effect. We utilized routinely collected monitoring
      samples (blood and scute), a commonly consumed tissue (muscle), and a classically
      analyzed tissue for environmental contaminants (liver) to demonstrate how the
      trace elements were distributed within the American alligator. We describe
      elemental tissue compartmentalization in an apex predator and investigate if
      noninvasive samples (blood and scute) can be used to estimate muscle tissue
      concentrations for a subset of elements measured. We found significant
      correlations for Hg, Rb, Se, Zn and Pb between noninvasive samples and consumed
      tissue and also found that Hg was the only trace metal of concern for this
      population of alligators. This study fills a gap in trace elemental analysis for
      reptilian apex predators in contaminated environments. Additionally,
      comprehensive elemental analysis of routinely collected samples can inform
      biomonitoring efforts and consumption advisories.

PMID- 28456037
TI  - Overexpression of Mn-superoxide dismutase in Oxya chinensis mediates increased
      malathion tolerance.
AB  - Superoxide dismutase (SOD) is the first line of defense against oxidative damage.
      Malathion is an organophosphate insecticide and can induce the production of
      reactive oxygen species (ROS) and cause the intracellular oxidative stress. The
      present study was undertaken to examine the effects of malathion on SODs activity
      and their transcriptional levels in Oxya chinensis (Thunberg) (Orthoptera:
      Acrididae). The results showed that total SOD and MnSOD activities increased as a
      dose-dependent manner while CuZnSOD activity has no significant changes after
      malathion treatments. Total SOD and MnSOD activities were the highest at the
      concentration of 0.8 MUg MUL-1 malathion treatment and increased significantly
      about 1.81- and 2.48-fold compared with the control, respectively. Increased mRNA
      expression of MnSOD, ecCuZnSOD1, and ecCuZnSOD2 were observed after malathion
      treatments. Moreover, the alteration of MnSOD transcript was similar to the
      profiles of MnSOD activity. These results suggested that the up-regulation
      expression of MnSOD transcript led to the increase of MnSOD activity in order to
      eliminate the excessive ROS caused by malathion. In addition, we evaluated the
      role of individual SOD gene in malathion stress by using RNAi and recombinant SOD
      proteins. The results showed that ROS contents increased significantly after the
      silencing of MnSOD and ecCuZnSOD1 genes. The OD values of the E. coli cells
      transformed with pET-28a-OcMnSOD plasmid were 1.13-1.31-fold and 1.08-1.33-fold
      higher than those of cells with pET-28a plasmids under 0.4 and 0.8 MUg MUL-1
      malathion treatments, respectively. These findings indicated that MnSOD exerted
      an important role in defense oxidative stress caused by malathion.

PMID- 28456038
TI  - Characteristic accumulation of PCDD/Fs in pine needles near an MSWI and emission
      levels of the MSWI in Pearl River Delta: A case study.
AB  - Pine needle samples were collected near a municipal solid waste incinerator
      (MSWI) in Pearl River Delta, southern China, as well as the stack gas and dust
      samples of the MSWI were simultaneously collected. Polychlorinated dibenzo-p
      dioxins and polychlorinated dibenzofurans (PCDD/Fs) were analyzed following the
      USEPA Method 1613B. The concentration of PCDD/Fs in the pine needles (137-625
      ng/kg, 25-51 ng I-TEQ/kg) is the highest level ever detected in China. Congener
      profile comparison and principal component analysis (PCA) confirmed the MSWI as
      an important emission source of environmental PCDD/Fs. The PCDD/Fs in the pine
      needles mainly depended on the atmospheric concentration, exposure time and also
      the wind direction. The accumulation of PCDD/Fs in this species did not occur at
      a steady rate, and the total concentrations covered up the actual photolysis
      information. Gas-phase partitioning of compounds in the atmosphere was the
      dominant process through which PCDD/Fs were adsorbed onto the pine needle surface
      in contrast with particle-phase deposition, and subsequent environmental behavior
      varied between the congeners. Photo-degradation was the major transformation
      process as PCDD/Fs were adsorbed onto the pine needle surfaces. Higher
      chlorinated PCDD/Fs were more recalcitrant to photo-degradation than those that
      were less chlorinated, and PCDDs were more resistant to photo-degradation than
      PCDFs. On the other hand, the strong ability of lipid-rich pine needles to
      accumulate dioxin compounds indicates they can be used as the absorption sink of
      PCDD/Fs in heavily polluted areas because it is easier to dispose of pine needles
      than it is to clean contaminated air.

PMID- 28456039
TI  - A note on unusual Si/Al ratios in PM10 and PM2.5 road dust at several locations
      in India.
AB  - The Si/Al ratios in road dust (PM10 and/or PM2.5) at several locations in India
      were examined and found to range between 1.6 and 84.9. The potential factors for
      this wide range of unusual Si/Al ratios in road dust are not known at this time.
      In addition to re-assessing data quality, the observations suggest the need to
      carefully quantify anthropogenic inputs of these elements to road dust. The
      findings of this study also contradict popular assumptions about minimal
      enrichment of crustal elements by anthropogenic sources and highlight the need to
      re-visit dust mass estimation using Si and Al as a surrogate. Further,
      characterization of Si/Al ratio in road dust at locations in India and the
      influence of local geology/geochemistry on it are especially important, if this
      ratio is to be used either for dust estimation or as an input to ambient aerosol
      mass source apportionment models.

PMID- 28456040
TI  - Nitrogen or phosphorus repletion strategies for enhancing lipid or carotenoid
      production from Tetraselmis marina.
AB  - The objective of this study was to investigate the accumulation of lipid and
      photosynthetic pigments from Tetraselmis marina. When the cells were grown in F/2
      medium for seven days in the first stage, the carotenoid and lipid contents, and
      productivity were 44g/kg (DW), 27% and 31mg/L/d, respectively. After second stage
      of cultivation of T. marina for further 3-days under N-replete condition (4.41mM
      NaNO3) increased biomass concentration of 1900mg/L and lipid content of 50% were
      observed, with an enhanced lipid productivity of 86.36mg/L/d and SFA and MUFA
      fractions of 70.76 and 13.14%, respectively. However, under P-repletion (2.08mM
      NaH2PO4), its carotenoid content increased to 89.23g/kg and its PUFA for 65% of
      total lipids. Results showed that N and P-replete conditions decreased SOD
      activity and increased H2O2 and TBARS levels of T. marina. Thus, this native
      microalga strain could be a potent candidate for feed,  food or biofuel
      production.

PMID- 28456041
TI  - Enhanced treatment of Fischer-Tropsch wastewater using up-flow anaerobic sludge
      blanket system coupled with micro-electrolysis cell: A pilot scale study.
AB  - The coupling of micro-electrolysis cell (MEC) with an up-flow anaerobic sludge
      blanket (UASB) system in pilot scale was established for enhanced treatment of
      Fischer-Tropsch (F-T) wastewater. The lowest influent pH (4.99+/-0.10) and
      reduced alkali addition were accomplished under the assistance of anaerobic
      effluent recycling of 200% (stage 5). Simultaneously, the optimum COD removal
      efficiency (93.5+/-1.6%) and methane production (2.01+/-0.13m3/m3.d) at the lower
      hydraulic retention time (HRT) were achieved in this stage. In addition, the
      dissolved iron from MEC could significantly increase the protein content of
      tightly bound extracellular polymeric substances (TB-EPS), which was beneficial
      to formation of stable granules. Furthermore, the high-throughput 16S rRNA gene
      pyrosequencing in this study further confirmed that Geobacter species could
      utilize iron oxides particles as electron conduit to perform the direct
      interspecies electron transfer (DIET) with Methanothrix, finally facilitating the
      syntrophic degradation of propionic acid and butyric acid and contributing
      completely methane production.

PMID- 28456043
TI  - Comparison of cadmium and lead sorption by Phyllostachys pubescens biochar
      produced under a low-oxygen pyrolysis atmosphere.
AB  - Phyllostachys pubescens (PP) biochars produced under a low oxygen pyrolysis
      atmosphere (oxygen content 1-4%) were prepared as sorbents for investigating the
      mechanisms of cadmium and lead sorption. A low-oxygen pyrolysis atmosphere
      increased biochar ash and specific surface area, promoting heavy metal
      precipitation and complexation. The maximum sorption capacity (Qm) of Pb2+
      obtained from the Langmuir model was 67.4mg.g-1, while Qm of Cd2+ was 14.7mg.g-1.
      The contribution of each mechanism varied with increasing oxygen content at a low
      pyrolysis temperature. Mineral precipitation with Pb2+ was the predominant
      mechanism for Pb2+ removal and the contribution proportion significantly
      increased from 17.2% to 71.7% as pyrolysis oxygen atmosphere increased from 0% to
      4%. The results showed that cadmium sorption primarily involved coordination with
      pi electrons, at 54.1-82.6% of the total adsorption capacity. The PP biochar
      shows potential for application in removing heavy metal contaminants, especially
      Pb2+.

PMID- 28456042
TI  - Approach of describing dynamic production of volatile fatty acids from sludge
      alkaline fermentation.
AB  - In this work, a mathematical model was developed to describe the dynamics of
      fermentation products in sludge alkaline fermentation systems for the first time.
      In this model, the impacts of alkaline fermentation on sludge disintegration,
      hydrolysis, acidogenesis, acetogenesis, and methanogenesis processes are
      specifically considered for describing the high-level formation of fermentation
      products. The model proposed successfully reproduced the experimental data
      obtained from five independent sludge alkaline fermentation studies. The modeling
      results showed that alkaline fermentation largely facilitated the disintegration,
      acidogenesis, and acetogenesis processes and severely inhibited methanogenesis
      process. With the pH increase from 7.0 to 10.0, the disintegration, acidogenesis,
      and acetogenesis processes respectively increased by 53%, 1030%, and 30% while
      methane production decreased by 3800%. However, no substantial effect on
      hydrolysis process was found. The model also indicated that the pathway of
      acetoclastic methanogenesis was more severely inhibited by alkaline condition
      than that of hydrogentrophic methanogenesis.

PMID- 28456044
TI  - Long-term impacts of titanium dioxide nanoparticles (TiO2 NPs) on performance and
      microbial community of activated sludge.
AB  - The long-term impacts of titanium dioxide nanoparticles (TiO2 NPs) on the
      performance and microbial community of activated sludge were evaluated in a
      sequencing batch reactor (SBR). TiO2 NPs impacted the COD and phosphorus removals
      of activated sludge, whereas the NH4+-N removal efficiency had no distinct change
      at 0-60mg/L TiO2 NPs. The presence of TiO2 NPs obviously inhibited the organic
      matter and nitrogen removal rates of activated sludge. The phosphorus removal
      rate gradually reduced at 0-5mg/L TiO2 NPs and then increased at 10-60mg/L TiO2
      NPs. The removal rates of organic matter, nitrogen and phosphorus had the similar
      varying trends to the corresponding microbial enzymatic activities. High TiO2 NPs
      concentration promoted more reactive oxygen species (ROS) production and lactate
      dehydrogenase (LDH) release of activated sludge. The microbial richness and
      diversity of activated sludge were obviously affected at the phyla, class and
      genus levels.

PMID- 28456045
TI  - Hydrothermal pretreatment and enzymatic hydrolysis of mixed green and woody
      lignocellulosics from arid regions.
AB  - Utilization of multi-specie feedstocks is imperative for application of
      lignocellulosic biorefineries in arid regions. Different lignocellulosic residues
      vary in composition and anatomical features. Pretreatment and enzymatic
      hydrolysis are two processes at the front end of any lignocellulosics biorefinery
      applying biochemical pathway, and have to efficiently deal with the variance in
      the feedstock composition and properties. However, there is limited knowledge
      about effect of mixing different lignocellulosics on pretreatment and enzymatic
      hydrolysis yields. In this study effect of mixing on the yields from hydrothermal
      pretreatment and enzymatic hydrolysis was analyzed by mixing three different
      lignocellulosic residues - Bermuda grass, Jasmine hedges, and date palm fronds.
      Results showed that the individual and the mixed lignocellulosics gave same
      yields when treated under similar conditions of hydrothermal pretreatment and
      enzymatic hydrolysis. It indicates that this mixture can be a suitable feedstock
      for lignocellulosic biorefinery.

PMID- 28456046
TI  - Maximization of monomeric C5 sugars from wheat bran by using mesoporous ordered
      silica catalysts.
AB  - The hydrolysis process of a real fraction of arabinoxylans derived from wheat
      bran was studied. The influence of catalyst type and loading, reaction time and
      different metal cations were discussed in terms of the hydrolysis yield of
      arabinose and xylose oligomers as well as the formation of furfural as
      degradation product. A high yield of arabinoxylans into the corresponding
      monomeric sugars (96 and 94% from arabino- and xylo-oligosaccharides,
      respectively) was obtained at relatively high temperatures (180 degrees C) and
      short reaction times (15min) with a catalyst loading of 4.8g of RuCl3/Al-MCM-48
      per g of initial carbon in hemicelluloses.

PMID- 28456047
TI  - Full-scale photobioreactor for biotreatment of olive washing water: Structure and
      diversity of the microalgae-bacteria consortium.
AB  - The performance of a full-scale photobioreactor (PBR) for the treatment of olive
      washing water (OWW) was evaluated under different HRTs (5-2days). The system was
      able to treat up to 3926L OWWday-1, and consisted of an activated-carbon
      pretreatment column and a tubular PBR unit (80 tubes, 98.17L volume, 2-m height,
      0.25m diameter). PBR was an effective and environmentally friendly method for the
      removal of phenols, COD, BOD5, turbidity and color from OWW (average efficiencies
      94.84+/-0.55%, 85.86+/-1.24%, 99.12+/-0.17%, 95.86+/-0.98% and 87.24+/-0.91%,
      respectively). The diversity of total bacteria and microalgae in the PBR was
      analyzed using Illumina-sequencing, evaluating the efficiency of two DNA
      extraction methods. A stable microalgae-bacteria consortium was developed
      throughout the whole experimentation period, regardless of changes in HRT,
      temperature or solar radiation. MDS analyses revealed that the interplay between
      green algae (Sphaeropleales), cyanobacteria (Hapalosiphon) and Proteobacteria
      (Rhodopseudomonas, Azotobacter) played important roles in OWW bioremediation.

PMID- 28456048
TI  - Polyamine-RNA-membrane interactions: From the past to the future in biology.
AB  - Biogenic polyamines (PAs), spermine, spermidine and putrescine are widely spread
      amino acid derivatives, present in living cells throughout the whole evolutionary
      scale. Their amino groups confer them a marked basic character at the cellular
      pH. We have tested the interaction of PAs with negatively-charged phospholipids
      in the absence and presence of nucleic acids (tRNA was mainly used for practical
      reasons). PAs induced aggregation of lipid vesicles containing acidic
      phospholipids. Aggregation was detected using both spectroscopic and fluorescence
      microscopy methods (the latter with giant unilamellar vesicles). PA-liposome
      complexes were partially disaggregated when nucleic acids were added to the
      mixture, indicating a competition between lipids and nucleic acids for PAs in a
      multiple equilibrium phenomenon. Equivalent observations could be made when
      vesicles composed of oleic acid and 1-decanol (1:1mol ratio) were used instead of
      phospholipid liposomes. The data could evoke putative primitive processes of
      proto-biotic evolution. At the other end of the time scale, this system may be at
      the basis of an interesting tool in the development of nanoscale drug delivery.

PMID- 28456049
TI  - Silk fibroin-Thelebolan matrix: A promising chemopreventive scaffold for soft
      tissue cancer.
AB  - Research of improved functional bio-mimetic matrix for regenerative medicine is
      currently one of the rapidly growing fields in tissue engineering and medical
      sciences. This study reports a novel bio-polymeric matrix, which is fabricated
      using silk protein fibroin from Bombyx mori silkworm and fungal exopolysaccharide
      Thelebolan from Antarctic fungus Thelebolus sp. IITKGP-BT12 by solvent
      evaporation and freeze drying method. Natural cross linker genipin is used to
      imprison the Thelebolan within the fibroin network. Different cross-linked and
      non-cross-linked fibroin/Thelebolan matrices are fabricated and biophysically
      characterized. Cross-linked thin films show robustness, good mechanical strength
      and high temperature stability in comparison to non-cross-linked and pure
      matrices. The 3D sponge matrices demonstrate good cytocompatibility.
      Interestingly, sustained release of the Thelebolan from the cross-linked matrices
      induce apoptosis in colon cancer cell line (HT-29) in time dependent manner while
      it is nontoxic to the normal fibroblast cells (L929).The findings indicate that
      the cross-linked fibroin/Thelebolan matrices can be used as potential topical
      chemopreventive scaffold for preclusion of soft tissue carcinoma.

PMID- 28456050
TI  - Erratum to "Analysing UK clinicians' understanding of cognitive symptoms in major
      depression: A survey of primary care physicians and psychiatrists" [J. Affect.
      Disord. 207 (2017) 346-352].

PMID- 28456051
TI  - Determinants of single family residential water use across scales in four western
      US cities.
AB  - A growing body of literature examines urban water sustainability with increasing
      evidence that locally-based physical and social spatial interactions contribute
      to water use. These studies however are based on single-city analysis and often
      fail to consider whether these interactions occur more generally. We examine a
      multi-city comparison using a common set of spatially-explicit water,
      socioeconomic, and biophysical data. We investigate the relative importance of
      variables for explaining the variations of single family residential (SFR) water
      uses at Census Block Group (CBG) and Census Tract (CT) scales in four
      representative western US cities - Austin, Phoenix, Portland, and Salt Lake City,
      - which cover a wide range of climate and development density. We used both
      ordinary least squares regression and spatial error regression models to identify
      the influence of spatial dependence on water use patterns. Our results show that
      older downtown areas show lower water use than newer suburban areas in all four
      cities. Tax assessed value and building age are the main determinants of SFR
      water use across the four cities regardless of the scale. Impervious surface area
      becomes an important variable for summer water use in all cities, and it is
      important in all seasons for arid environments such as Phoenix. CT level analysis
      shows better model predictability than CBG analysis. In all cities, seasons, and
      spatial scales, spatial error regression models better explain the variations of
      SFR water use. Such a spatially-varying relationship of urban water consumption
      provides additional evidence for the need to integrate urban land use planning
      and municipal water planning.

PMID- 28456052
TI  - Cultural differences in the imitation and transmission of inefficient actions.
AB  - Across two studies, we explored cultural differences in children's imitation and
      transmission of inefficient actions. Chinese American and Caucasian American
      preschoolers (N=115) viewed either one or three models using two inefficient
      tools to perform two different tasks. In the video, when the model(s) performed
      the task, only the inefficient tool was available; thus, their choice to use that
      tool could be considered rational. Next, children were invited to complete the
      task with either the inefficient tool or an efficient alternative. Whereas the
      two cultural groups imitated a single model at similar rates, Chinese American
      children imitated significantly more than Caucasian American children after
      viewing a consensus. Similar results were found when exploring differences in
      information transmission. The Chinese American children were significantly more
      likely than their Caucasian American peers to instruct using an inefficient tool
      when they had initially viewed a consensus demonstrate it. We discuss these
      findings with respect to differences in children's use of social versus task
      specific cues for learning and teaching.

PMID- 28456053
TI  - Simulation-based training for nurses: Systematic review and meta-analysis.
AB  - BACKGROUND: Simulation-based training is a widespread strategy to improve health
      care quality. However, its effect on registered nurses has previously not been
      established in systematic reviews. The aim of this systematic review is to
      evaluate effect of simulation-based training on nurses' skills and knowledge.
      METHODS: We searched CDSR, DARE, HTA, CENTRAL, CINAHL, MEDLINE, Embase, ERIC, and
      SveMed+ for randomised controlled trials (RCT) evaluating effect of simulation
      based training among nurses. Searches were completed in December 2016. Two
      reviewers independently screened abstracts and full-text, extracted data, and
      assessed risk of bias. We compared simulation-based training to other learning
      strategies, high-fidelity simulation to other simulation strategies, and
      different organisation of simulation training. Data were analysed through meta
      analysis and narrative syntheses. GRADE was used to assess the quality of
      evidence. RESULTS: Fifteen RCTs met the inclusion criteria. For the comparison of
      simulation-based training to other learning strategies on nurses' skills, six
      studies in the meta-analysis showed a significant, but small effect in favour of
      simulation (SMD -1.09, CI -1.72 to -0.47). There was large heterogeneity (I2
      85%). For the other comparisons, there was large between-study variation in
      results. The quality of evidence for all comparisons was graded as low.
      CONCLUSION: The effect of simulation-based training varies substantially between
      studies. Our meta-analysis showed a significant effect of simulation training
      compared to other learning strategies, but the quality of evidence was low
      indicating uncertainty. Other comparisons showed inconsistency in results. Based
      on our findings simulation training appears to be an effective strategy to
      improve nurses' skills, but further good-quality RCTs with adequate sample sizes
      are needed.

PMID- 28456054
TI  - Nightmares and nonsuicidal self-injury: The mediating role of emotional
      dysregulation.
AB  - INTRODUCTION: Nonsuicidal self-injury (NSSI) is a transdiagnostic behavior
      associated with significant psychopathology. Research has shown a positive
      association between sleep disturbances, (e.g., nightmares and insomnia), and
      suicidal behavior, however, the relation between NSSI and sleep disturbances has
      yet to be examined. Sleep disturbances have been found to have a causal role in
      problems with emotional dysfunction. Specifically, sleep disturbances inhibit the
      emotion processing function of sleep. Importantly, a majority of individuals
      engage in NSSI to regulate intense emotions, and it is possible that sleep
      disturbances increase propensity for NSSI by contributing to dysregulated
      emotions. METHODS: In two cross-sectional studies, the present research examined
      whether insomnia symptoms and nightmares were related to NSSI in a clinical
      sample (Study 1, N = 313) and in a university sample (Study 2, N = 152).
      Furthermore, the hypothesis that emotional dysregulation would atemporally
      mediate the relationship between sleep disturbances and NSSI was tested in Study
      2. RESULTS: Findings showed that nightmares, but not insomnia symptoms, were
      associated with NSSI while controlling for depressive symptoms. This pattern of
      findings was consistent across both clinical and university samples, which
      underscores the robustness of the finding. Further, the relationship between
      nightmares and NSSI was fully mediated by emotional dysregulation. CONCLUSION:
      The present research provides initial evidence that nightmares are atemporally
      associated with an increased propensity for NSSI by contributing to emotional
      dysregulation, and provides support for the emotion regulation function of
      dreams.

PMID- 28456055
TI  - Unraveling molecular pathways of poorly differentiated neuroendocrine carcinomas
      of the gastroenteropancreatic system: A systematic review.
AB  - BACKGROUND: Poorly differentiated neuroendocrine carcinomas (NECs) are rare and
      aggressive tumors. Their molecular pathogenesis is still largely unknown, and
      consequently, the best therapeutic management also remains to be determined. We
      conducted a systematic review on molecular alterations found in
      gastroenteropancreatic NECs (GEP-NECs) and discuss potential applications of
      targeted therapies in setting. MATERIALS AND METHODS: Systematic review of
      studies about molecular features in tumor tissues of patients with GEP-NECs. The
      Medline, Lilacs, Embase, Cochrane, Scopus and Opengrey databases were sought,
      without time, study design or language restrictions. RESULTS: Of the 1.564
      studies retrieved, 41 were eligible: 33 were retrospective studies and eight were
      case reports. The studies spanned the years 1997-2017 and involved mostly
      colorectal, stomach and pancreas primary tumors. Molecular alterations in the
      TP53 gene and the p53 protein expression were the most commonly observed,
      regardless of the primary site. Other consistently found molecular alterations
      were microsatellite instability (MSI) in approximately 10% of gastric and
      colorectal NEC, and altered signaling cascades of p16/Rb/cyclin D1, Hedgehog and
      Notch pathways, and somatic mutations in KRAS, BRAF, RB1 and Bcl2. In studies of
      mixed adeno-neuroendocrine carcinomas (MANECs) the molecular features of GEP-NEC
      largely resemble their carcinoma/adenocarcinomas tumor counterparts. CONCLUSIONS:
      Despite the paucity of data about the molecular drivers associated with GEP-NEC,
      some alterations may be potentially targeted with new cancer-directed therapies.
      Collaborative clinical trials for patients with advanced GEP-NEC are urgently
      needed.

PMID- 28456056
TI  - Virus population dynamics during infection.
AB  - During RNA virus infection of a host, error-prone viral replication will give
      rise to a cloud of genetically-linked mutants, as well as truncated, defective
      genomes. In this review, we describe the dynamics of viral diversity during
      infection, illustrating that the viral population fluctuates greatly in number of
      genomes and composition of mutants, in relation with the existence of physical
      barriers or immune pressures. We illustrate the importance of generating
      diversity by analyzing the case of fidelity variants, largely attenuated in vivo.
      Recombination is also considered in its various roles: redistribution of
      mutations on full-length genomes, and production of highly-immunostimulatory
      defective genomes. We cover these notions by underlining, when they exist, the
      differences between acute and persistent infections.

PMID- 28456057
TI  - Wrist MR imaging in children: Effect on clinical diagnosis and management.
AB  - OBJECTIVES: Evaluate the impact of wrist MRI in children on clinical diagnosis
      and management. MATERIALS AND METHODS: Four year retrospective analysis including
      demographics, MRI diagnoses, and effect on diagnoses and management were
      determined. RESULTS: 101 patients were included. Wrist MRI altered management in
      86% (95% CI: 77-92%) and diagnosis in 46% (36-56%) of patients. MRI changed both
      diagnosis and management in 41% (31-51%), changed management only in 46% (35
      56%), changed diagnosis only in 5% (2-12%), and had no change in diagnosis or
      management in 9% (95% CI: 4-17%). CONCLUSION: Wrist MRI in children changes
      clinical diagnosis and management in a substantial proportion of cases.

PMID- 28456058
TI  - "Warning: This image has been digitally altered": The effect of disclaimer labels
      added to fashion magazine shoots on women's body dissatisfaction.
AB  - The present experiment aimed to investigate the impact of the addition of
      disclaimer labels to fashion magazine shoots on women's body dissatisfaction.
      Participants were 320 female undergraduate students who viewed fashion shoots
      containing a thin and attractive model with no disclaimer label, or a small,
      large, or very large disclaimer label, or product images. Although thin-ideal
      fashion shoot images resulted in greater body dissatisfaction than product
      images, there was no significant effect of disclaimer label. Internalisation of
      the thin ideal was found to moderate the effect of disclaimer label, such that
      internalisation predicted increased body dissatisfaction in the no label and
      small label conditions, but not in the larger label conditions. Overall, the
      results showed no benefit for any size of disclaimer label in ameliorating the
      negative effect of viewing thin-ideal media images. It was concluded that more
      extensive research is required before the effective implementation of disclaimer
      labels.

PMID- 28456059
TI  - Stimulation of human gingival fibroblasts viability and growth by roots treated
      with high intensity lasers, photodynamic therapy and citric acid.
AB  - OBJECTIVE: The aim of this study was to compare the effect of root
      biomodification by lasers, citric acid and antimicrobial photodynamic therapy
      (aPDT) on viability and proliferation of human gingival fibroblasts (FGH).
      DESIGN: Groups were divided in control (CC - only cells), and root fragments
      treated by: scaling and root planing (positice control - SC), Er:YAG (ER
      60mJ,10pps,10Hz,10s,2940nm), Nd:YAG (ND-0.5W,15Hz,10s,1640nm), antimicrobial
      photodynamic therapy (PDT-InGaAIP,30mW,45J/cm2,30s,660nm,toluidine blue O),
      citric acid plus tetracycline (CA). Fibroblasts (6th passage, 2*103) were
      cultivated in a 24-h conditioned medium by the treated root fragments. Cell
      viability was measured by MTT test at 24, 48, 72 and 96h. In a second experiment,
      FGH cells (104) were cultivated on root fragments which received the same
      treatments. After 24, 48, 72h the number of cells was counted in SEM pictures. In
      addition, chemical elements were analyzed by energy dispersive spectroscopy
      (EDS). Data was analyzed by two-way ANOVA (first experiment), repeated measures
      ANOVA (second experiment) and ANOVA (EDS experiment) tests complemented by
      Tukey's test (p<0.05). RESULTS: ND, PDT and CA promoted higher cell viability
      (p<0.05). ND and ER groups presented higher number of cells on root surfaces
      (p<0.05). ER group presented higher calcium and CA group a higher carbon
      percentages (p<0.05). CONCLUSIONS: All treatments but scaling and root planing
      stimulated fibroblast viability while Er:YAG and Nd:YAG treated root surfaces
      presented higher number of cells.

PMID- 28456060
TI  - Sample treatment procedures for environmental sensing and biosensing.
AB  - During the last years, a lot of efforts have been put into developing novel
      sensors and biosensors systems for monitoring the occurrence of emerging
      pollutants in the environment. These analyses are often challenging because of
      the variety of physico-chemical properties of these substances, the extremely
      diluted concentrations at which they can be found, and the intrinsic complexity
      of environmental matrices. In order to improve the (bio)sensors' performance,
      preconcentration/pretreatment techniques may be implemented. The automatization
      of these systems results in an autonomous, straight-forward alternative to
      classic chromatography-based methods, which in addition can operate remotely with
      real-time or pseud-real-time measurements. The present review offers an overview
      about these potentially automatable extraction techniques and provides some
      references about their recent use in environmental sensing and biosensors.

PMID- 28456061
TI  - Switchable Cas9.
AB  - Ever since its discovery, Cas9 from Streptococcus pyogenes has revolutionized
      biology by enabling analysis and engineering of genomes with unprecedented
      precision and ease. To fine-tune on-target effects and to mitigate adverse
      effects caused by untimely and off-target action of Cas9, strategies have been
      developed to control its activity at the post-translational stage via external
      trigger signals. Control is either achieved by modifying the Cas9 protein itself
      or its programmable RNA molecules. To date, switchable Cas9 variants responding
      to small ligands, light or temperature have been engineered. With these variants
      in hand, the regulation and modification of genomes can be accomplished in graded
      and ever more precise manner.

PMID- 28456062
TI  - Uncovering degrees of workplace bullying: A comparison of baccalaureate nursing
      students' experiences during clinical placement in Australia and the UK.
AB  - Bullying in health workplaces has a negative impact on nurses, their families,
      multidisciplinary teams, patient care and the profession. This paper compares the
      experiences of Australian and UK baccalaureate nursing students in relation to
      bullying and harassment during clinical placement. A secondary analysis was
      conducted on two primary cross-sectional studies of bullying experiences of
      Australian and UK nursing students. Data were collected using the Student
      Experience of Bullying during Clinical Placement (SEBDCP) questionnaire and
      analysed using descriptive and inferential statistics. The total sample was 833
      Australian and 561 UK students. Australian nursing students experienced a higher
      rate of bullying (50.1%) than UK students (35.5%). Students identified other
      nurses as the main perpetrators (Aust 53%, UK 68%), although patients were the
      main source of physical acts of bullying. Few bullied students chose to report
      the episode/s. The main reason for non-reporting was fear of being victimised.
      Sadly, some students felt bullying and harassment was 'part of the job'. A
      culture of bullying in nursing persists internationally. Nursing students are
      vulnerable and can question their future in the 'caring' profession of nursing
      after experiencing and/or witnessing bullying during clinical placement. Bullying
      requires a zero tolerance approach. Education providers must develop clearer
      policies and implement procedures to protect students - the future nursing
      workforce.

PMID- 28456063
TI  - Ocular findings in adult subjects with an inactivating mutation in GH releasing
      hormone receptor gene.
AB  - OBJECTIVE: Ocular function is fundamental for environmental adaptation and
      survival capacity. Growth factors are necessary for a mature eyeball, needed for
      adequate vision. However, the consequences of the deficiency of circulating
      growth hormone (GH) and its effector insulin-like growth factor I (IGF-I) on the
      physical aspects of the human eye are still debated. A model of untreated
      isolated GH deficiency (IGHD), with low but measurable serum GH, may clarify this
      issue. The aim of this study was to assess the ocular aspects of adult IGHD
      individuals who have never received GH therapy. DESIGN: Cross sectional study.
      METHODS: Setting: University Hospital, Federal University of Sergipe, Brazil.
      PATIENTS: Twenty-five adult (13 males, mean age 50.1years, range 26 to 70years
      old) IGHD subjects homozygous for a null mutation (c.57+1G>A) in the GHRH
      receptor gene, and 28 (15 males, mean age 51.1years, range 26 to 67years old)
      controls were submitted to an endocrine and ophthalmological assessment. Forty
      six IGHD and 50 control eyes were studied. MAIN OUTCOME MEASURES: Visual acuity,
      intraocular pressure, refraction (spherical equivalent), ocular axial length
      (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous depth (VD),
      mean corneal curvature (CC) and central corneal thickness (CCT). RESULTS: IGHD
      subjects exhibited unmeasurable serum IGF-I levels, similar visual acuity,
      intraocular pressure and LT, higher values of spherical equivalent and CC, and
      lower measures of AL, ACD, VD and CCT in comparison to controls, but within their
      respective normal ranges. While mean stature in IGHD group was 78% of the control
      group, mean head circumference was 92% and axial AL was 96%. CONCLUSIONS: These
      observations suggest mild ocular effects in adult subjects with severe IGF-I
      deficiency due to non-treated IGHD.

PMID- 28456064
TI  - Effects of diclofenac on the expression of Nrf2 and its downstream target genes
      in mosquito fish (Gambusia affinis).
AB  - Diclofenac (DCF) is one of widely used non-steroidal anti-inflammatory drugs.
      Recently, this drug has been universally detected in aquatic environment.
      However, its potential adverse effects and oxidative stress toxic mechanisms on
      fish remain unclear. In the present study, we first cloned the crucial partial
      sequences of some key oxidative stress related genes, which include NF-E2-related
      factor 2 (Nrf2), NAD(P)H: quinoneoxidoreductase (NQO1), glutamate-cysteine ligase
      catalytic subunit (GCLC), Cu-Zn superoxide dismutase (SOD2), catalase (CAT),
      alpha-glutathione S-transferase (GSTA), and UDP-glucuronosyltransferases (UGT) in
      mosquito fish (Gambusia affinis). We also deduced amino acids of Nrf2 and then
      constructed the phylogenetic trees of Nrf2, NQO1 and GCLC, respectively. Results
      showed that a high identity percentage was founded between G. affinis and other
      bony fish species, such as Xiphophorus maculates and Poecilia reticulate. The
      transcriptional expression of these genes and partly related enzymes activities
      were then investigated under the included environmental relevant concentration
      DCF exposure (0MUmolL-1, 1.572*10-3MUmolL-1, 1.572*10-2MUmolL-1, 0.1572MUmolL-1
      and 1.572MUmolL-1) for 24h and 168h. The expression of Nrf2 was inhibited at 24h
      but induced at 168h, exhibiting a significant time and/or dose-effect
      relationship under DCF exposure. Similar observation was found in its downstream
      target genes. However, Nrf2-mediated antioxidant enzymes activities displayed
      differently under the same concentration of DCF exposure for the same time. Under
      DCF exposure for 168h, the genes exhibited dramatic induction trend, but there
      were no significant changes in enzyme activities and MDA content. Overall, mRNA
      responses were more sensitive than enzyme changes in mosquito fish under DCF
      exposure.

PMID- 28456065
TI  - Improving HIV post-exposure prophylaxis rates after pediatric acute sexual
      assault.
AB  - The purpose of our study was to increase the rate of children with appropriate
      HIV-PEP regimens among those diagnosed with sexual assault in The Children's
      Hospital of Philadelphia Emergency Department (ED). The outcome measure was the
      percent of patients receiving correct HIV-PEP. We retrospectively reviewed 97
      charts over 31 months to define the baseline rate of children receiving
      appropriate HIV-PEP regimens (pre QI-implementation period: 2/2012-8/2014). Among
      children in which HIV-PEP was indicated following sexual assault, 40% received
      the recommended 28-day course. Root cause analysis indicated prescribing errors
      accounted for 87% of patients not receiving appropriate HIV-PEP. Process drivers
      included standardizing care coordination follow-up calls to elicit specific
      information about HIV-PEP, ED educational initiatives targeted at HIV-PEP
      prescribing, revision of the clinical pathway to specify indicated duration of
      HIV-PEP, and revision of the order set to auto-populate the number of days for
      the HIV-PEP prescription. During the QI-implementation period (9/2014-4/2015),
      the rate of appropriate HIV-PEP increased to 64% (median 60%) and the average
      number of days between incorrect HIV-PEP regimens was 24.5. Post QI
      implementation (5/2015-3/2016), the rate of appropriate HIV-PEP increased to 84%
      (median 100%) and the average number of days between incorrect HIV-PEP regimens
      increased to 78.4. A multifaceted quality improvement process improved the rate
      of receipt of appropriate HIV-PEP regimens for pediatric victims of sexual
      assault. Decision support tools are instrumental in sustaining ideal care
      delivery, but require ongoing evaluation and improvement in order to remain
      optimally effective.

PMID- 28456066
TI  - Dissociation mediates the relationship between sexual abuse and child
      psychological difficulties.
AB  - The aim of the present study was to evaluate, using structural equation modeling,
      a theoretical model in which dissociation is a core process mediating the
      relationship between childhood sexual abuse (CSA) and internalizing,
      externalizing, and sexualized behaviour difficulties in children. A total of 290
      children aged 2-12 participated in this study in Quebec, Canada from 1998 to
      2004, including 138 children with histories of CSA and 152 non-abused children.
      To assess child dissociative symptoms, internalizing and externalizing
      difficulties, as well as sexualized behaviour difficulties, the Child
      Dissociative Checklist, the Child Behaviour Checklist and the Child Sexualized
      Behaviour Inventory were completed by parents. Dissociation mediated the
      relationship between CSA and internalizing, externalizing, and sexualized
      behaviour difficulties, with the model explaining respectively 42.5%, 49.9% and
      33.9% of the variance of these difficulties. Findings are consistent with a model
      where dissociation is a common pathway linking CSA and child psycho-sexual
      difficulties.

PMID- 28456067
TI  - Unpacking the parallel effects of parental alcohol misuse and low income on risk
      of supervisory neglect.
AB  - Although low income status and parent alcohol misuse are considered critical risk
      factors for child neglect, little is known about the mechanisms of this
      association. No known research has assessed the parallel effect of each on
      occurrence of child neglect. This study aimed to explore the direct and indirect
      effects of parent alcohol misuse and low family income on risk of supervisory
      neglect through mediating factors such as parent depressive symptoms and low
      social support. The study used a sample of 2990 parents of children under 13
      years old who completed a listed telephone survey conducted in 50 mid-sized
      cities within California during 2009. We used a structural equation model to
      estimate the direct and indirect effects of parent alcohol misuse (defined as
      heavy drinking frequency) and low family income on supervisory neglect toward a
      focal child, as well as the indirect effect via parental depressive symptoms and
      low social support. Mediation analysis to capture direct, indirect, and total
      effects of these two independent variables was also conducted. Results revealed a
      significant direct effect of low family income on likelihood of supervisory
      neglect. Low income also exhibited an indirect effect via increased depressive
      symptoms and low social support. Annual frequency of heavy drinking showed no
      direct effect on supervisory neglect likelihood, but an indirect effect was
      observed via increased depressive symptoms and decreased social support. Parent
      low income and high frequency heavy drinking likely increase risks for
      supervisory neglect through distinct pathways. Longitudinal research is needed to
      confirm the pathways identified within this study.

PMID- 28456068
TI  - Summary of comparison between FFT-CW(r) and Usual Care sample from Administration
      for Children's Services.
AB  - This evaluation compared the efficiency and effectiveness of Functional Family
      Therapy-Child Welfare (FFT-CW(r), n=1625) to Usual Care (UC: n=2250) in reducing
      child maltreatment. FFT-CW(r) is a continuum of care model based on the family's
      risk status. In a child welfare setting, families received either UC or FFT-CW(r)
      in a quasi-experimental, stepped wedge design across all five boroughs of New
      York City. The families were matched using stratified propensity scoring on their
      pre-service risk status and followed for 16 months. The ethnically diverse sample
      included African American (36%), Asian (4%); Hispanic (49%), and Non-Hispanic
      White (6%) or Other (6%) participants. Referral reasons included abuse or neglect
      (57.4%), child service needs (56.9%) or child health and safety concerns (42.8%).
      Clinical process variables included staff fidelity, service duration, and number
      of contacts. Positive outcomes included whether all clinical goals were met and
      negative outcomes included transfers, outplacement, recurring allegations and
      service participation within 16 months of the case open date. Families receiving
      FFT-CW(r) completed treatment more quickly than UC and they were significantly
      more likely to meet all of the planned service goals. Higher treatment fidelity
      was associated with more favorable outcomes. Fewer FFT-CW(r) families were
      transferred to another program at closing, and they had fewer recurring
      allegations. FFT-CW(r) had fewer out-of-home placements in families with higher
      levels of risk factors. The FFT-CW(r) program was more efficient in completing
      service, and more effective than UC in meeting treatment goals while also
      avoiding adverse outcomes.

PMID- 28456069
TI  - Child maltreatment in U.S. emergency departments: Imaging and admissions.
AB  - OBJECTIVE: We report imaging and admission ratios for children with definitive
      and suggestive maltreatment in a national sample of emergency departments (EDs).
      METHODS: Using the 2012 Nationwide Emergency Department Sample (NEDS), we
      generated national estimates of ED visits for children <10 years with both
      definitive and suggestive maltreatment. Outcomes were admission/transfer ratios
      for children <10years and screening ratios by skeletal surveys and head computed
      tomography (CT) for children <2 years with suspected physical abuse. We compared
      hospitals with low, medium, and high pediatric ED volumes using multivariable
      logistic regression. RESULTS: The 2012 national estimate of U.S. ED visits
      (children <10years) with definitive maltreatment is 14,457 (95% CI: 11,987
      16,928). Suggestive child maltreatment was seen in an additional 103,392 (95% CI:
      90,803-115,981) pediatric ED visits. After controlling for patient case mix, high
      volume hospitals had a significantly higher adjusted odds ratio (AOR) of
      admission/transfer among definitive cases (AOR=1.74, 95% CI: 1.08-2.81), and
      medium volume hospitals had a higher odds of admission/transfer among suggestive
      cases (AOR=1.24, 95% CI: 1.02-1.50) when compared with low volume hospitals. In
      hospitals with reliable reporting of imaging procedures, high volume hospitals
      reported skeletal surveys (age <2 years) significantly more often than low volume
      hospitals, AOR=3.32 (95% CI: 1.25-8.84); the AORs for head CT did not differ by
      hospital volume. CONCLUSIONS: Low volume hospitals were less likely to screen by
      skeletal survey, but head CT ratios were not affected by ED volume. Low volume
      hospitals were also less likely to admit or transfer.

PMID- 28456070
TI  - Ponticulus posticus: Morphometric analysis and Its anatomical Implications for
      occipito-cervical fusion.
AB  - OBJECTIVE: The purpose of this study was to evaluate the morphometric
      characteristics of ponticulus posticus (PP) and determine the impact of two
      promising high cervical operations (posterior arch to lateral mass screw fixation
      (PALMSF) and occipital condyle fixation (OCF)). PATIENTS AND METHODS: We
      evaluated retrospective data from a total of 2628 head and neck 3-dimensional CT
      angiographies (3D-CTA) that did not have bony or vascular abnormalities. The PP
      anomaly cases were confirmed, then we measured vertebral artery groove height
      (VAGH), arch to vertebral artery distance (AVD) and posterior arch height (PAH)
      for PALMSF. We also measured the vertebral artery to occipital bone distance
      (VOD) for OCF. RESULTS: In 186 patients (7.1%), 227 PP (complete or near
      complete) were identified and this anomaly was more common in males and on the
      left side. The mean VAGH and PAH values ranged from 5.0 to 6.0mm and from 7.0 to
      8.8mm, respectively. The VAGH value was not statistically different, regardless
      of the presence of PP, and the feasibility (>4mm) of a safe PALMSF (range, 87.7
      100%) was not influenced by PP anomalies. The mean value of VOD in the anomaly
      side (range, 6.0-8.0mm) was much higher than for normal side (range, 4.2-5.7mm)
      and the proportion of patients that had a safe OCF (>3.5mm) was also much higher
      (range, 90.8-96.9%) than for the normal side. CONCLUSIONS: A PP anomaly might
      have some anatomical feasibility and advantage during PALMSF and OCF, due to the
      relatively sufficient bony (VAGH) and spatial regions (VOD). However, there are
      gender differences in anatomical dimensions (VAGH, VOD and AVD); therefore,
      surgery in female patients should be approached more cautiously in the future.

PMID- 28456071
TI  - Gender-related differences in aneurysmal subarachnoid hemorrhage: A hospital
      based study.
AB  - OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) is more common in women
      than in men. Despite its clinical relevance, knowledge about the potential gender
      differences in the clinical course and outcome of aSAH is sparse - we aimed at
      elucidating such differences. PATIENTS AND METHODS: Retrospective cohort study
      including patients >=18years of age with aSAH admitted to an interdisciplinary
      intensive-care center at the University Hospital of Bern (Switzerland). RESULTS:
      The study included 120 patients with aSAH. Sixty-nine percent of the enrolled
      patients were women. The women were older than men (mean [standard deviation] age
      58+/-13years vs. 51+/-12years, P=0.006), and were increasingly overrepresented
      across increasing age-strata. Global disease severity at admission, measured by
      the APACHE II score, was higher in women than in men (median score 18 points [IQR
      12-26] vs. 14 points [IQR 10-19], P=0.006). Men and women had similar medical
      histories and severity of aSAH. We found no evidence for major differences in the
      adopted aneurysm-securing strategy and intensive care interventions. At 6 months
      from aSAH, mortality was higher in women than men (28% vs. 16%), but this did not
      reach statistical significance (P=0.25). APACHE II, but not gender, was
      associated with unfavorable outcome at 6 months. CONCLUSION: Women outnumbered
      men among aSAH patients, especially along increasing age strata, and had
      increased global disease severity on admission. No other significant differences
      between genders were found.

PMID- 28456072
TI  - Can smartphone mental health interventions reduce symptoms of anxiety? A meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Various psychological interventions are effective for reducing
      symptoms of anxiety when used alone, or as an adjunct to anti-anxiety
      medications. Recent studies have further indicated that smartphone-supported
      psychological interventions may also reduce anxiety, although the role of mobile
      devices in the treatment and management of anxiety disorders has yet to be
      established. METHODS: We conducted a systematic review and meta-analysis of all
      randomized clinical trials (RCTs) reporting the effects of psychological
      interventions delivered via smartphone on symptoms of anxiety (sub-clinical or
      diagnosed anxiety disorders). A systematic search of major electronic databases
      conducted in November 2016 identified 9 eligible RCTs, with 1837 participants.
      Random-effects meta-analyses were used to calculate the standardized mean
      difference (as Hedges' g) between smartphone interventions and control
      conditions. RESULTS: Significantly greater reductions in total anxiety scores
      were observed from smartphone interventions than control conditions (g=0.325, 95%
      C.I.=0.17-0.48, p<0.01), with no evidence of publication bias. Effect sizes from
      smartphone interventions were significantly greater when compared to
      waitlist/inactive controls (g=0.45, 95% C.I.=0.30-0.61, p<0.01) than active
      control conditions (g=0.19, 95% C.I.=0.07-0.31, p=0.003). LIMITATIONS: The extent
      to which smartphone interventions can match (or exceed) the efficacy of
      recognised treatments for anxiety has yet to established. CONCLUSIONS: This meta
      analysis shows that psychological interventions delivered via smartphone devices
      can reduce anxiety. Future research should aim to develop pragmatic methods for
      implementing smartphone-based support for people with anxiety, while also
      comparing the efficacy of these interventions to standard face-to-face
      psychological care.

PMID- 28456073
TI  - Affective temperaments in anorexia nervosa: The relevance of depressive and
      anxious traits.
AB  - BACKGROUND: Affective temperaments have been so far understudied in anorexia
      nervosa (AN) despite the relevance of personality and both affective and anxious
      comorbidity with regard to vulnerability, course, and outcome of this deadly
      disorder. METHODS: Ninety-eight female inpatients diagnosed with AN and 131
      healthy controls (HCs) were enrolled in this study and completed the Temperament
      Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) in
      addition to assessments of eating psychopathology, depression, and anxiety.
      RESULTS: AN patients and HCs differed in all affective temperaments. The
      diagnostic subtypes of AN differed as well with binge-purging individuals being
      more cyclothymic and anxious than those with restricting-type AN. TEMPS-A scores
      correlated with body mass index and eating psychopathology but not with duration
      of illness. Concerning comorbidity, grater scores on the depressive and lower
      scores on the hyperthymic temperaments were found in depressed patients. Those
      who had either an anxious or irritable temperament were significantly more
      diagnosed with an anxious disorder than those who did not show this temperament.
      When logistic regression was performed, high depressive/low hyperthymic and high
      irritable/anxious traits resulted to be associated with depressive and anxious
      comorbidity, respectively, independently of confounding factors. LIMITATIONS:
      Cross-sectional design, some patients on medications, few baseline clinical
      differences between diagnostic subtypes, no other personality assessments.
      CONCLUSIONS: An affective continuum strongly associated with mood and anxious
      comorbidity emerged in AN. Such an evaluation could have several research and
      clinical implications given the need of improving treatment individualization and
      early interventions for such a complex disorder.

PMID- 28456074
TI  - The paradox of public holidays: Hospital-treated self-harm and associated
      factors.
AB  - BACKGROUND: Recent research on the patterns of self-harm around public holidays
      is lacking. This study used national data to examine the patterns of hospital
      treated self-harm during public holidays, and to examine associated factors.
      METHODS: Data on self-harm presentations to all emergency departments were
      obtained from the National Self-Harm Registry Ireland. The association between
      self-harm presentations and public holidays was examined using univariate and
      multivariate Poisson regression analyses. RESULTS: A total of 104,371
      presentations of self-harm were recorded between 2007 and 2015. The mean number
      of self-harm presentations was 32 on public holidays. St. Patrick's Day had the
      highest number of presentations compared to all other public holidays, with a
      daily mean of 44 presentations. Across all years, self-harm presentations during
      public holidays had a 24% increased risk of involving alcohol consumption
      compared to all other days and this effect was most pronounced during the
      Christmas period. The association with alcohol remained significant at a
      multivariate level. Presentations on public holidays were more likely to attend
      out of normal working hours. An increase in male presentations involving self
      cutting was observed on public holidays and there was an over-representation of
      males presenting for the first time. LIMITATIONS: It is likely that extent of
      alcohol involvement in self-harm presentations reported here is an underestimate,
      as it was dependent on the information being recorded by the attending clinician.
      CONCLUSIONS: Public holidays are associated with an elevated number of self-harm
      presentations to hospital, with presentations to hospital involving alcohol
      significantly increased on these days. Hospital resources should be targeted to
      address increases during public holidays, including during out-of-hours.
      Involvement of alcohol may delay delivery of care to these patients in emergency
      settings.

PMID- 28456075
TI  - Associations between pain and depression in nursing home patients at different
      stages of dementia.
AB  - BACKGROUND: Pain is associated with depression in nursing home patients with
      dementia. It is, however, unclear whether pain increases depression. Therefore we
      evaluated the prospective associations between pain and depressive symptoms in
      nursing home patients at different stages of cognitive impairment. METHODS: Two
      longitudinal studies were combined, including 931 patients (>=65 years) from 65
      nursing homes. One study assessed patients at admission, with 6-month follow-up
      (2012-2014). The other study assessed residents with varying lengths of stay,
      with 4-month follow-up (2014-2015). Patients were assessed with the Mini-Mental
      State Examination, the Mobilisation-Observation-Behaviour-Intensity-Dementia-2
      Pain Scale, and the Cornell Scale for Depression in Dementia. RESULTS: At
      baseline, 343 patients (40% of 858 assessed) had moderate to severe pain, and 347
      (38% of 924) had depression. Pain increased the risk of depression (OR 2.35, 95%
      CI 1.76-3.12). Using mixed model analyses, we found that a 1-point increase in
      pain was associated with a .48 increase in depression (p<.001). This association
      persisted in mild, moderate, and severe cognitive impairment. In those recently
      admitted, depressive symptoms decreased over time, and having less pain at follow
      up was associated with a decrease in depressive symptoms (within-subject effect;
      p=.042). LIMITATIONS: The two cohorts had different inclusion criteria, which may
      reduce generalisability. The study design does not allow conclusions on
      causality. CONCLUSIONS: Pain and depressive symptoms are associated in patients
      with dementia. Because reduced pain is associated with less depressive symptoms,
      these patients should be assessed regularly for untreated pain. The benefit of
      analgesic treatment should be weighed carefully against the potential for adverse
      effects.

PMID- 28456076
TI  - A novel antigen delivery system induces strong humoral and CTL immune responses.
AB  - New strategies with the ability to enhance both the humoral and cellular immune
      responses remain a priority for the development of future therapeutic cancer
      vaccines. In this study, we took advantage of beta-glucan particles (GPs) derived
      from Saccharomyces cerevisiae baker's yeast and a novel reverse micro-emulsion
      method to prepare an antigen-loaded GP carrier system for dendritic cell (DC)
      specific antigen delivery, followed by careful evaluation of the immune functions
      of the prepared particles in initiating both the humoral and cellular immune
      responses through in vitro and in vivo experiments. The prepared particles
      greatly promoted DC activation and cytokine production and cross presented the
      antigen to CD8 cells, inducing very strong OVA specific humoral and cellular
      immune responses. Treatment with these particles significantly prevented the
      growth of implanted EG7-OVA tumors in a prophylactic and pre-established tumor
      model. These results suggest that our strategy may be able to be utilized as a
      promising platform for cancer immunotherapy.

PMID- 28456077
TI  - Chitosan degradation products facilitate peripheral nerve regeneration by
      improving macrophage-constructed microenvironments.
AB  - Chitosan-based artificial nerve grafts have been widely employed to repair
      peripheral nerve defects. Our previous study has shown that chitosan constructed
      nerve graft not only provides suitable scaffolds for nerve regeneration, its
      degradation products, chitooligosaccharides (COS), also promote nerve repair.
      However, the involved mechanisms are still not fully elucidated. In the present
      study, we observed that pro-inflammatory cytokines, as well as macrophage
      infiltration, were transiently up-regulated in the injured sciatic nerves which
      were bridged with silicon tubes filled with COS. Based upon transcriptome
      analysis, the axis of miR-327/CCL2 in Schwann cells (SCs) was identified as a
      potential target of COS. The following experiments have confirmed that COS
      stimulate CCL2 expression by down-regulating miR-327 in SCs. Consequently, the
      resulting CCL2 induces macrophage migration at injury sites to re-construct
      microenvironments and thus facilitates nerve regeneration. Collectively, our data
      provide a theoretical basis for the clinical application of chitosan-based grafts
      in peripheral nerve regeneration.

PMID- 28456078
TI  - Significant enhancement by biochar of caproate production via chain elongation.
AB  - In this study, biochar was introduced into a chain elongation system to enhance
      the bioproduction of caproate and caprylate. The concentration of caproate
      increased to 21.1 g/L upon the addition of biochar, which is the highest level of
      caproate reported for such a system to date when ethanol was used as electron
      donor. The addition of biochar created a tougher system with more stable
      microorganism community structure for chain elongation, in which no obvious
      inhibition by products or substrates was observed, moreover, the lag phase was
      reduced 2.3-fold compared to the system without biochar. These reinforcement
      effect of biochar are attributed to the enhanced conductivity due to the
      significant enrichment of functional microorganisms via the microbial network
      surrounding smaller biochar particles, and via the adsorption on the rough
      surfaces or pores of larger particles, which facilitated electron transfer.
      Higher amounts of extracellular polymer substances and higher conductivity
      induced by biochar could contribute to the reinforcement effect in chain
      elongation.

PMID- 28456079
TI  - Temporal variations analyses and predictive modeling of microbiological seawater
      quality.
AB  - Bathing water quality is a major public health issue, especially for tourism
      oriented regions. Currently used methods within EU allow at least a 2.2 day
      period for obtaining the analytical results, making outdated the information
      forwarded to the public. Obtained results and beach assessment are influenced by
      the temporal and spatial characteristics of sample collection, and numerous
      environmental parameters, as well as by differences of official water standards.
      This paper examines the temporal variation of microbiological parameters during
      the day, as well as the influence of the sampling hour, on decision processes in
      the management of the beach. Apart from the fecal indicators stipulated by the EU
      Bathing Water Directive (E. coli and enterococci), additional fecal (C.
      perfringens) and non-fecal (S. aureus and P. aeriginosa) parameters were
      analyzed. Moreover, the effects of applying different evaluation criteria
      (national, EU and U.S. EPA) to beach ranking were studied, and the most common
      reasons for exceeding water-quality standards were investigated. In order to
      upgrade routine monitoring, a predictive statistical model was developed. The
      highest concentrations of fecal indicators were recorded early in the morning (6
      AM) due to the lack of solar radiation during the night period. When compared to
      enterococci, E. coli criteria appears to be more stringent for the detection of
      fecal pollution. In comparison to EU and U.S. EPA criteria, Croatian national
      evaluation criteria provide stricter public health standards. Solar radiation and
      precipitation were the predominant environmental parameters affecting beach water
      quality, and these parameters were included in the predictive model setup.
      Predictive models revealed great potential for the monitoring of recreational
      water bodies, and with further development can become a useful tool for the
      improvement of public health protection.

PMID- 28456080
TI  - Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4
      dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging.
AB  - INTRODUCTION: Several 11C and 18F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA)
      analogues have been used for neurologic and oncologic diseases, especially for
      brain tumors and neuroendocrine tumors PET imaging. However, 18F-labeled N
      substituted l-DOPA analogues have not been reported so far. In the current study,
      radiosynthesis and biological evaluation of a new 18F-labeled l-DOPA analogue, N
      (2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine ([18F]FPDOPA) for tumor
      PET imaging are performed. METHODS: The synthesis of [18F]FPDOPA was via a two
      step reaction sequence from 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). The
      biodistribution of [18F]FPDOPA was determined in normal Kunming mice. In vitro
      competitive inhibition and protein incorporation experiments were performed with
      SPC-A-1 lung adenocarcinoma cell lines. PET/CT studies of [18F]FPDOPA were
      conducted in C6 rat glioma and SPC-A-1 human lung adenocarcinoma and H460 human
      large cell lung cancer-bearing nude mice. RESULTS: [18F]FPDOPA was prepared with
      a decay-corrected radiochemical yield of 28+/-5% and a specific activity of 50+/
      15GBq/MUmol (n=10) within 125min. In vitro cell experiments showed that
      [18F]FPDOPA uptake in SPC-A-1 cells was primarily transported through Na+
      independent system L, with Na+-dependent system B0,+ and system ASC partly
      involved in it. Biodistribution data in mice showed that renal-bladder route was
      the main excretory system of [18F]FPDOPA. PET imaging demonstrated intense
      accumulation of [18F]FPDOPA in several tumor xenografts, with (8.50+/-0.40)%ID/g
      in C6 glioma, (6.30+/-0.12)%ID/g in SPC-A-1 lung adenocarcinoma, and (6.50+/
      0.10)%ID/g in H460 large cell lung cancer, respectively. CONCLUSION: A novel N
      substituted 18F-labeled L-DOPA analogue [18F]FPDOPA is synthesized and evaluated
      in vitro and in vivo. The results support that [18F]FPDOPA seems to be a
      potential PET tracer for tumor imaging, especially be a better potential PET
      tracer than [18F]fluoro-2-deoxy-d-glucose ([18F]FDG) for brain tumor imaging.

PMID- 28456082
TI  - Application of spectroscopic methods (FT-IR, Raman, ECD and NMR) in studies of
      identification and optical purity of radezolid.
AB  - In the presented study, N-{[(5S)-3-(2-fluoro-4'-{[(1H-1,2,3-triazol-5
      ylmethyl)amino]methyl}biphenyl-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
      (radezolid) was synthesized and characterized using FT-IR, Raman, ECD and NMR.
      The aim of this work was to assess the possibility of applying classical spectral
      methods such as FT-IR, Raman, ECD and NMR spectroscopy for studies on the
      identification and optical purity of radezolid. The experimental interpretation
      of FT-IR and Raman spectra of radezolid was conducted in combination with
      theoretical studies. Density functional theory (DFT) with the B3LYP hybrid
      functional was used for obtaining radezolid spectra. Full identification was
      carried out by COSY, 1H {13C} HSQC and 1H {13C} HMBC experiments. The
      experimental NMR chemical shifts and spin-spin coupling constants were compared
      with theoretical calculations using the DFT method and B3LYP functional employing
      the 6-311++G(d,p) basis set and the solvent polarizable continuum model (PCM).
      The experimental ECD spectra of synthesized radezolid were compared with
      experimental spectra of the reference standard of radezolid. Theoretical
      calculations enabled us to conduct HOMO and LUMO analysis and molecular
      electrostatic potential maps were used to determine the active sites of
      microbiologically active form of radezolid enantiomer. The relationship between
      results of ab initio calculations and knowledge about chemical-biological
      properties of S-radezolid and other oxazolidinone derivatives are also discussed.

PMID- 28456081
TI  - Gamma-tocotrienol profoundly alters sphingolipids in cancer cells by inhibition
      of dihydroceramide desaturase and possibly activation of sphingolipid hydrolysis
      during prolonged treatment.
AB  - Vitamin E gamma-tocotrienol (gammaTE) is known to have anticancer effects, but
      mechanisms underlying these actions are not clear. Here using liquid
      chromatography tandem mass spectrometry, we show that gammaTE induced marked
      changes of sphingolipids including rapid elevation of dihydrosphingosine and
      dihydroceramides (dhCers) in various types of cancer cells. The elevation of
      dihydrosphingolipids coincided with increased cellular stress, as indicated by
      JNK phosphorylation, and was prior to any sign of induction of apoptosis.
      Chemically blocking de novo synthesis of sphingolipids partially counteracted
      gammaTE-induced apoptosis and autophagy. Experiments using 13C3, 15N-labeled l
      serine together with enzyme assays indicate that gammaTE inhibited cellular
      dihydroceramide desaturase (DEGS) activity without affecting its protein
      expression or de novo synthesis of sphingolipids. Unlike the effect on dhCers,
      gammaTE decreased ceramides (Cers) after 8-h treatment but increased C18:0-Cer
      and C16:0-Cer after 16 and 24 h, respectively. The increase of Cers coincides
      with gammaTE-induced apoptosis and autophagy. Since gammaTE inhibits DEGS and
      decreases de novo Cer synthesis, elevation of Cers during prolonged gammaTE
      treatment is likely caused by sphingomeylinase-mediated hydrolysis of
      sphingomyelin. This idea is supported by the observation that an acid
      sphingomeylinase inhibitor partially reversed gammaTE-induced cell death. Our
      study demonstrates that gammaTE altered sphingolipid metabolism by inhibiting
      DEGS activity and possibly by activating SM hydrolysis during prolonged treatment
      in cancer cells.

PMID- 28456083
TI  - Microfluidic photoinduced chemical oxidation for Ru(bpy)33+ chemiluminescence - A
      comprehensive experimental comparison with on-chip direct chemical oxidation.
AB  - For the first time, the analytical figures of merit in detection capabilities of
      the very less explored photoinduced chemical oxidation method for Ru(bpy)32+ CL
      has been investigated in detail using 32 structurally different analytes. It was
      carried out on-chip using peroxydisulphate and visible light and compared with
      well-known direct chemical oxidation approaches using Ce(IV). The analytes belong
      to various chemical classes such as tertiary amine, secondary amine,
      sulphonamide, betalactam, thiol and benzothiadiazine. Influence of detection
      environment on CL emission with respect to method of oxidation was evaluated by
      changing the buffers and pH. The photoinduced chemical oxidation exhibited more
      universal nature for Ru(bpy)32+ CL in detection towards selected analytes. No
      additional enhancers, reagents, or modification in instrumental configuration
      were required. Wide detectability and enhanced emission has been observed for
      analytes from all the chemical classes when photoinduced chemical oxidation was
      employed. Some of these analytes are reported for the first time under
      photoinduced chemical oxidation like compounds from sulphonamide, betalactam,
      thiol and benzothiadiazine class. On the other hand, many of the selected
      analytes including tertiary and secondary amines such as cetirizine, azithromycin
      fexofenadine and proline did not produced any analytically useful CL signal
      (S/N=3 or above for 1MUgmL-1 analyte) under chemical oxidation. The most
      fascinating observations was in the detection limits; for example ofloxacin was
      15 times more intense with a detection limit of 5.81*10-10M compared to most
      lowest ever reported 6*10-9M. Earlier, penicillamine was detected at 0.1MUgmL-1
      after derivatization using photoinduced chemical oxidation, but in this study, we
      improved it to 5.82ngmL-1 without any prior derivatization. The detection limits
      of many other analytes were also found to be improved by several orders of
      magnitude under photoinduced chemical oxidation.

PMID- 28456084
TI  - Bio-functions and molecular carbohydrate structure association study in forage
      with different source origins revealed using non-destructive vibrational
      molecular spectroscopy techniques.
AB  - The objectives of this study were to: 1) investigate forage carbohydrate
      molecular structure profiles; 2) bio-functions in terms of CHO rumen degradation
      characteristics and hourly effective degradation ratio of N to OM (HEDN/OM), and
      3) quantify interactive association between molecular structures, bio-functions
      and nutrient availability. The vibrational molecular spectroscopy was applied to
      investigate the structure feature on a molecular basis. Two sourced-origin
      alfalfa forages were used as modeled forages. The results showed that the
      carbohydrate molecular structure profiles were highly linked to the bio-functions
      in terms of rumen degradation characteristics and hourly effective degradation
      ratio. The molecular spectroscopic technique can be used to detect forage
      carbohydrate structure features on a molecular basis and can be used to study
      interactive association between forage molecular structure and bio-functions.

PMID- 28456085
TI  - Single sensor for multiple analytes in different optical channel: Applying for
      multi-ion response modulation.
AB  - A Schiff-base, (2,4-di-tert-butyl-6-((2-hydroxyphenyl-imino)-methyl)phenol) (L),
      has been improved to function as a simultaneous multi-ion probe in different
      optical channel. The probe changes from colorless to orangish upon being
      deprotonated by F-, while the presence of Al3+ significantly enhances the
      fluorescence of the probe due to the inhibition of CN isomerization, cation
      induced inhibition of excited-state intramolecular proton transfer (ESIPT), and
      chelation enhanced fluorescence (CHEF). Dual-channel "off-on" switching behavior
      resulted from the sequential input of F- and Al3+, reflecting the balance of
      independent reactions of Al3+ and F- with L and with one another. This sensing
      phenomenon realizes transformation between multiple states and beautifully mimics
      a "Write-Read-Erase-Read" logic circuit with two feedback loops.

PMID- 28456086
TI  - Quantum chemical studies on structural, vibrational, nonlinear optical properties
      and chemical reactivity of indigo carmine dye.
AB  - Structural and vibrational spectroscopic studies were performed on indigo carmine
      (IC) isomers using FT-IR spectral analysis along with DFT/B3LYP method utilizing
      Gaussian 09 software. GaussView 5 program has been employed to perform a detailed
      interpretation of vibrational spectra. Simulation of infrared spectra has led to
      an excellent overall agreement with the observed spectral patterns. Mulliken
      population analyses on atomic charges, MEP, HOMO-LUMO, NLO, first order
      hyperpolarizability and thermodynamic properties have been examined by
      (DFT/B3LYP) method with the SDD basis set level. Density of state spectra (DOS)
      were calculated using GaussSum 3 at the same level of theory. Molecular modeling
      approved that DOS Spectra are the most significant tools for differentiating
      between two IC isomers so far. Moreover, The IC isomers (cis-isomer) have shown
      an extended applicability for manufacturing both NLO and photovoltaic devices
      such as solar cells.

PMID- 28456087
TI  - Fluorescent and colorimetric detection of Fe(III) and Cu(II) by a difunctional
      rhodamine-based probe.
AB  - A new rhodamine B hydrazone derivative (probe L) was synthesized and
      characterized. The probe L had sufficiently satisfactory selective response to
      Fe3+ and Cu2+ ions among various interferential metal ions, and high sensitivity
      with the detection limit of 4.63*10-9M and 5.264*10-7M for Fe3+ and Cu2+ ions,
      respectively. In the presence of Fe3+, the probe L exhibited turn-on orange
      fluorescence accompanied by color change from colorless to pink. Toward Cu2+, the
      probe L showed significant color change from colorless to red purple. These
      remarkable orange fluorescence and color change made probe L suitable naked-eye
      identify for Fe3+ and Cu2+ ions. By means of Job's plot, Benesi-Hildebrand
      studies and FTIR spectra, both 1:1 binding modes (L-Fe3+ and L-Cu2+) were
      confirmed. The coordination mechanism and turn on/off fluorescence for L-Fe3+ and
      L-Cu2+ complexes were well explained by theoretical calculations. Moreover, probe
      L could be used as a quick, simple, visual test strip for Fe3+ and Cu2+
      detection.

PMID- 28456088
TI  - Neural correlates of infants' sensitivity to vocal expressions of peers.
AB  - Responding to others' emotional expressions is an essential and early developing
      social skill among humans. Much research has focused on how infants process
      facial expressions, while much less is known about infants' processing of vocal
      expressions. We examined 8-month-old infants' processing of other infants'
      vocalizations by measuring event-related brain potentials (ERPs) to positive
      (infant laughter), negative (infant cries), and neutral (adult hummed speech)
      vocalizations. Our ERP results revealed that hearing another infant cry elicited
      an enhanced negativity (N200) at temporal electrodes around 200ms, whereas
      listening to another infant laugh resulted in an enhanced positivity (P300) at
      central electrodes around 300ms. This indexes that infants' brains rapidly
      respond to a crying peer during early auditory processing stages, but also
      selectively respond to a laughing peer during later stages associated with
      familiarity detection processes. These findings provide evidence for infants'
      sensitivity to vocal expressions of peers and shed new light on the neural
      processes underpinning emotion processing in infants.

PMID- 28456089
TI  - The 30-year experience-A meta-analysis of randomised and high-quality non
      randomised studies of hyperthermic intraperitoneal chemotherapy in the treatment
      of gastric cancer.
AB  - IMPORTANCE: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used
      within various multimodality strategies for the prevention and treatment of
      gastric cancer peritoneal carcinomatosis. OBJECTIVE: To systematically evaluate
      the role of HIPEC in gastric cancer and clarify its effectiveness at different
      stages of peritoneal disease progression. DATA SOURCES: Medline and Embase
      databases between January 1, 1985 and June 1, 2016. STUDY SELECTION: Randomised
      control trials and high-quality non-randomised control trials selected on a
      validated tool (methodological index for non-randomised studies) comparing HIPEC
      and standard oncological management for the treatment of advanced stage gastric
      cancer with and without peritoneal carcinomatosis were considered. DATA
      EXTRACTION AND SYNTHESIS: A random-effects network meta-analysis. MAIN OUTCOMES
      AND MEASURES: The primary outcomes were overall survival and disease recurrence.
      Secondary outcomes were overall complications, type of complications, and sites
      of recurrence. RESULTS: A total of 11 RCTs and 21 non-randomised control trials
      (2520 patients) were included. For patients without the presence of peritoneal
      carcinomatosis (PC), the overall survival rates between the HIPEC and control
      groups at 3 or 5 years resulted in favour of the HIPEC group (risk ratio [RR] =
      0.82, P = 0.01). No difference in the 3-year overall survival (RR = 0.99, P =
      0.85) in but a prolonged median survival of 4 months in favour of the HIPEC group
      (WMD = 4.04, P < 0.001) was seen in patients with PC. HIPEC was associated with
      significantly higher risk of complications for both patients with PC (RR = 2.15,
      P < 0.01) and without (RR = 2.17, P < 0.01). This increased risk in the HIPEC
      group was related to systemic drugs toxicity. Anastomotic leakage rates were
      found to be similar between groups. CONCLUSIONS: Our study demonstrates a
      survival advantage of the use of HIPEC as a prophylactic strategy and suggests
      that patients whose disease burden is limited to positive cytology and limited
      nodal involvement may benefit the most from HIPEC. For patients with extensive
      carcinomatosis, the completeness of cytoreductive surgery is a critical
      prognostic factor for survival. Future RCTs should better define patient
      selection criteria.

PMID- 28456090
TI  - Dynamic evaluation of circulating tumour cells in patients with advanced gastric
      and oesogastric junction adenocarcinoma: Prognostic value and early assessment of
      therapeutic effects.
AB  - BACKGROUND: The identification of dynamic biomarkers in advanced gastric and
      oesogastric junction adenocarcinoma (GOA) could help to tailor strategies for
      each patient. Enumeration of circulating tumour cells (CTCs) is approved by the
      US Food and Drug Administration in breast, colon and prostate cancer but is not
      in advanced GOA. Our study aims to establish the optimal threshold and the
      clinical significance of CTC count in advanced GOA before and during treatment.
      METHODS: One hundred six patients with untreated advanced GOA were included in
      the ancillary study of the PRODIGE 17-ACCORD 20 trial. CTCs were detected in the
      peripheral blood using the CellSearch system on day 0 (D0) and day 28 (D28). The
      prognostic value of CTCs at D0 and D28 was analysed by testing several
      thresholds. RESULTS: At baseline, median CTC count was 1 (range, 0-415). While
      CTCs >=1, 2 or 3 at D0 were all significantly associated with worse overall
      survival (OS) and progression-free survival (PFS), CTCs >=2 were the optimal
      threshold, on D0 or D28. CTCs >=2 at D28 were also predictive of disease control.
      Taking into account both D0 and D28 CTC count defined 3 groups (low/low, high/low
      and low-high/high) with significantly different PFS (p = 0.0002) and OS (p =
      0.003). CONCLUSION: Quantification of CTCs at baseline and during treatment may
      be a useful prognostic tool in advanced GOA, as it is associated with worse PFS
      and OS. A threshold >=2 CTCs seems to have the best discriminant value. Change in
      CTC count between baseline and D28 could help to tailor treatment to each
      individual patient.

PMID- 28456091
TI  - Prediction of the conditions for the consumption of game by Polish consumers.
AB  - Due to the changing needs of consumers and the increased risk of diet-related
      diseases, today's consumers are forced to seek alternative types of meat. It
      should, on one hand be tasty, and on the other will improve the health of the
      consumer. Game is considered to be such a meat. Although Poland is one of the
      leading producers and exporters of game in Europe, the level of its consumption
      is very low at about 0.08kg/person/year. Based on quantitative data from 1000
      respondents a model predicting the consumption of wild game based on logistic
      regression has been prepared. It was demonstrated that consumers are likely to
      increase their consumption of game, provided that it will have a higher quality
      and greater commercial availability. A higher propensity to change eating habits
      in respect of game was displayed mainly by men, city dwellers and those who
      evaluated their own knowledge on nutritional and diet higher than others.

PMID- 28456092
TI  - Occupation and risk of prostate cancer in Canadian men: A case-control study
      across eight Canadian provinces.
AB  - BACKGROUND: The etiology of prostate cancer continues to be poorly understood,
      including the role of occupation. Past Canadian studies have not been able to
      thoroughly examine prostate cancer by occupation with detailed information on
      individual level factors. METHODS: Occupation, industry and prostate cancer were
      examined using data from the National Enhanced Cancer Surveillance System, a
      large population-based case-control study conducted across eight Canadian
      provinces from 1994 to 1997. This analysis included 1737 incident cases and 1803
      controls aged 50 to 79 years. Lifetime occupational histories were used to group
      individuals by occupation and industry employment. Odds ratios and 95% confidence
      intervals were calculated and adjustments were made for known and possible risk
      factors. RESULTS: By occupation, elevated risks were observed in farming and farm
      management (OR=1.37, 95% CI 1.02-1.84), armed forces (OR=1.33, 95% CI 1.06-1.65)
      and legal work (OR=2.58, 95% CI 1.05-6.35). Elevated risks were also observed in
      office work (OR=1.20, 95% CI 1.00-1.43) and plumbing (OR=1.77, 95% CI 1.07-2.93)
      and with >=10 years duration of employment. Decreased risks were observed in
      senior management (OR=0.65, 95% CI 0.46-0.91), construction management (OR=0.69,
      95% CI 0.50-0.94) and travel work (OR=0.37, 95% CI 0.16-0.88). Industry results
      were similar to occupation results, except for an elevated risk in
      forestry/logging (OR=1.54, 95% CI 1.06-2.25) and a decreased risk in primary
      metal products (OR=0.70, 95% CI 0.51-0.96). CONCLUSION: This study presents
      associations between occupation, industry and prostate cancer, while accounting
      for individual level factors. Further research is needed on potential job
      specific exposures and screening behaviours.

PMID- 28456093
TI  - Differences in velocity-information processing between two areas in the auditory
      cortex of mustached bats.
AB  - The bio-sonar pulse of the mustached bat, Pteronotus parnellii parnellii,
      consists of four harmonics of constant frequency (CF1-4) and frequency-modulated
      (FM1-4) components. The CF and FM components carry velocity and distance
      information, respectively. In the auditory cortex of mustached bats, the CC ("C"
      stands for constant frequency) and DIF (dorsal intrafossa) areas consist of CF/CF
      neurons tuned to a combination of pulse CF1 and echo CFn (n = 2 or 3). They show
      facilitative responses to pulse-echo stimuli with specific frequency differences,
      corresponding to Doppler shifts. Their facilitative responses are sharply tuned
      to a specific relative target velocity (best velocity). Compared with CC neurons,
      DIF neurons are tuned to higher velocities and to larger CF1 amplitudes, and
      adapt faster to repetitive pulse-echo stimuli. The great majority of CC neurons
      are suited for the processing of velocity information during cruising and target
      directed flight, whereas the majority of DIF neurons are suited for the
      processing of velocity information when the bat is emitting loud pulses at low
      repetition rates during cruising flight. CC and DIF neurons are broadly tuned to
      0-2-ms echo delays and not suited for ranging.

PMID- 28456094
TI  - New biologics in the treatment of rare glomerular diseases of childhood.
AB  - Minimal change disease and focal segmental glomerulosclerosis are rare but
      important causes of end-stage kidney disease in children. Though their
      pathogenesis is still unclear, evidence of immune abnormalities provided the
      background for the use of immunosuppressive drugs, such as corticosteroids,
      calcineurin inhibitors, antiproliferative and alkylating agents. Unfortunately,
      these treatments fail to achieve a sustained remission in a significant portion
      of patients and are burdened by significant toxicities. Recent developments of
      new biologics, including anti-CD20 monoclonal antibodies rituximab and
      ofatumumab, offered the opportunity to selectively target immune cell subsets or
      activation pathways, leading to more effective and safer hypothesis-driven
      treatments.

PMID- 28456095
TI  - A survey of medical examiner death certification of vignettes on death in
      epilepsy: Gaps in identifying SUDEP.
AB  - OBJECTIVE: Lack of standardized terminology on death certificates (DCs) of SUDEP
      type cases may obscure the presence of epilepsy in these deaths. Most DCs for
      individuals dying unexpectedly with epilepsy are certified by medical examiners
      (MEs). The purpose of this study was to gauge death certification practices of
      MEs when interpreting SUDEP cases and assess implications for valid surveillance
      of SUDEP. MATERIALS AND METHODS: A survey consisting of clinical vignettes
      describing deaths in individuals with epilepsy was sent to medical examiners.
      Respondents were asked to indicate how they would certify death on a DC. Similar
      text responses were aggregated and coded according to the 10th revision of the
      International Statistical Classification of Diseases and Related Health Problems
      (ICD-10) coding system. RESULTS: A total of 847 responses on 11 cases were
      received. Depending upon the vignette, the proportion of responses within each
      case that did not have an ICD-10 seizure code ranged from 3% to 62%. G40.9
      (Epilepsy, unspecified) resulted from 43% of responses, and R56.8 (Other and
      unspecified convulsion) resulted from 38% of responses. CONCLUSION: The survey
      indicates that a high proportion of DCs do not have a seizure code and would not
      be identified utilizing these ICD-10 codes. The complicated nature of deaths in
      SUDEP, unclear circumstances surrounding a given death, and the lack of
      familiarity with SUDEP by surviving relatives may all contribute to variable
      terminology used to certify SUDEP deaths. Our results emphasize the need for
      collaboration between neurologists and forensic pathologists to develop a more
      uniform approach to death certification in SUDEP that will facilitate SUDEP
      research and inform relatives of individuals who die of SUDEP.

PMID- 28456097
TI  - Structure-guided cancer blockade between bioactive bursehernin and proteins:
      Molecular docking and molecular dynamics study.
AB  - Bursehernin (5'-desmethoxyyatein) is a natural lignan, which has anti-tumor
      activity in vitro. In this study, the binding-inhibitory effects of bursehernin
      were screening on selected 80 proteins associated with cancer pathway. The
      computational analysis suggested inhibitory effect due to bursehernin towards
      proteins related to cancer proliferation, including FMS kinase receptor, heat
      shock protein 90-alpha (Hsp90-alpha), adenylate cyclase 10 (ADCY10), mitogen
      activated protein kinase kinase (MEK1), and alpha-tubulin. Moreover, bursehernin
      could interfere with cell cycle progression via binding to cyclin B proteins.
      Among all screened proteins, the compound showed an interesting binding affinity
      to the FMS kinase receptor. The binding mode studies by molecular dynamic
      technique showed that aromatic ring of bursehernin compound was responsible for
      compound-protein interaction through pi-pi stacking with Tyr105 and Phe178 of the
      FMS kinase receptor. This study suggests that bursehernin has potential for
      development as an anti-tumor agent with an anti-proliferation, and cell cycle
      arrest inducing, although further studies are needed.

PMID- 28456098
TI  - Intentional switching in auditory selective attention: Exploring age-related
      effects in a spatial setup requiring speech perception.
AB  - Using a binaural-listening paradigm, age-related differences in the ability to
      intentionally switch auditory selective attention between two speakers, defined
      by their spatial location, were examined. Therefore 40 normal-hearing
      participants (20 young, O 24.8years; 20 older O 67.8years) were tested. The
      spatial reproduction of stimuli was provided by headphones using head-related
      transfer-functions of an artificial head. Spoken number words of two speakers
      were presented simultaneously to participants from two out of eight locations on
      the horizontal plane. Guided by a visual cue indicating the spatial location of
      the target speaker, the participants were asked to categorize the target's number
      word into smaller vs. greater than five while ignoring the distractor's speech.
      Results showed significantly higher reaction times and error rates for older
      participants. The relative influence of the spatial switch of the target-speaker
      (switch or repetition of speaker's direction in space) was identical across age
      groups. Congruency effects (stimuli spoken by target and distractor may evoke the
      same answer or different answers) were increased for older participants and
      depend on the target's position. Results suggest that the ability to
      intentionally switch auditory attention to a new cued location was unimpaired
      whereas it was generally harder for older participants to suppress processing the
      distractor's speech.

PMID- 28456096
TI  - Identifying low density lipoprotein cholesterol associated variants in the
      Annexin A2 (ANXA2) gene.
AB  - BACKGROUND AND AIMS: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein
      convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2
      binds to PCSK9, blocking its ability to promote degradation of low-density
      lipoprotein cholesterol-receptors (LDL-R) and thereby regulate low-density
      lipoprotein cholesterol (LDL-C) levels. Here we identify variants in ANXA2
      influencing LDL-C levels and we determine the molecular mechanisms of their
      effects. RESULTS: The ANXA2 single nucleotide polymorphism (SNP) genotype
      phenotype association was examined using the Second-Northwick-Park Heart Study
      (NPHSII) (n~2700) and the UCL-LSHTM-Edinburgh-Bristol (UCLEB) consortium
      (n~14,600). The ANXA2-R1 domain coding-SNP rs17845226 (V98L) associated with LDL
      C, homozygotes for the minor allele having ~18.8% higher levels of LDL-C (p =
      0.004), and higher risk of coronary heart disease (CHD) (p = 0.04). The SNP is in
      modest linkage disequilibrium (r2 > 0.5) with two intergenic SNPs, rs17191344 and
      rs11633032. Both SNPs showed allele-specific protein binding, and the minor
      alleles caused significant reduction in reporter gene expression (~18%, p <
      0.001). In the expression quantitative trait loci (eQTL) study, minor allele
      homozygotes have significantly lower levels of ANXA2-mRNA expression (p = 1.36 *
      10-05). CONCLUSIONS: Both rs11633032 and rs17191344 SNPs are functional variants,
      where the minor alleles create repressor-binding protein sites for transcription
      factors that contribute to reduced ANXA2 gene expression. Lower AnxA2 levels
      could increase plasma levels of PCSK9 and thus increase LDL-C levels and risk of
      CHD. This supports, for the first time in humans, previous observations in mouse
      models that changes in the levels of AnxA2 directly influence plasma LDL-C
      levels, and thus implicate this protein as a potential therapeutic target for LDL
      C lowering.

PMID- 28456099
TI  - Thyroid disorders and mammographic density in Spanish women: Var-DDM study.
AB  - OBJECTIVES: The association between breast cancer (BC) and thyroid disorders has
      been widely explored with unclear results. Mammographic density (MD) is one of
      the strongest risk factor for BC. This study explores the relationship between
      thyroid diseases and MD in Spanish women. MATERIALS & METHODS: This cross
      sectional study covered 2883 women aged 47-71 years participating in 7 BC
      screening programs in 2010. They allowed access to their mammograms, had
      anthropometrical-measures taken, and answered a telephonic epidemiological
      interview which included specific questions on thyroid diseases. Percentage of MD
      was assessed with a semiautomatic-computer tool (DM-scan) by two trained
      radiologists. We calculated the geometric mean of MD percentages (mean MD).
      Multivariable mixed linear regression models with random screening-center
      specific intercepts were fitted, using log-transformed percentage of MD as
      dependent variable and adjusting for age, body mass index, menopausal status and
      other confounders. ebeta represents the relative increase of mean MD. RESULTS:
      13.9% of the participants reported personal history of thyroid disease. MD was
      not associated to hyperthyroidism (ebeta:1.05, 95%CI: 0.82-1.36), hypothyroidism
      (ebeta:1.02, 95%CI: 0.75-1.38), thyroid nodules (ebeta:1.01, 95%CI: 0.85-1.19) or
      thyroid cancer (ebeta:1.03, 95%CI: 0.56-1.92). However, women with goiter had
      lower MD (mean MDno-goiter: 13.4% vs mean MDgoiter: 10.6%; ebeta:0.79, 95%CI:
      0.64-0.98) and those with Hashimoto thyroiditis had higher MD (mean MDno
      thyroiditis: 13.3% vs mean MDthyroidits: 25.8%; ebeta:1.94, 95%CI: 1.00-3.77).
      CONCLUSION: Functional thyroid disorders were not related to MD. However, MD was
      lower in women with goiter and higher in those reporting Hashimoto's thyroiditis.
      These relationships should be confirmed in future studies.

PMID- 28456101
TI  - Magnetically separable and recyclable Fe3O4@SiO2/isoniazide/Pd nanocatalyst for
      highly efficient synthesis of biaryls by Suzuki coupling reactions.
AB  - This report contains the procedure implemented in the preparation of
      Fe3O4@SiO2/isoniazide/Pd as a novel magnetic nanocatalyst, in which isoniazide
      groups are utilized (as linkers) to secure palladium nanoparticles (Pd NPs) to
      the Fe3O4 exterior without agglomeration. The resultant catalyst was
      characterized through performing transmission electron microscopy (TEM), scanning
      electron microscopy (SEM), wavelength-dispersive X-ray spectroscopy (WDX), X-ray
      powder diffraction (XRD), Fourier transform infrared (FTIR), inductively coupled
      plasma (ICP), Energy-dispersive X-ray spectroscopy (EDS), vibrating sample
      magnetometer (VSM) and X-ray photoelectron spectroscopy (XPS). The catalytic
      behavior of Fe3O4@SiO2/isoniazide/Pd was investigated to synthesis of biaryl
      compounds by Suzuki coupling reactions. Interestingly, the novel catalyst was
      able to be recovered and recycled six times without any noticeable loss in
      activity.

PMID- 28456100
TI  - Area-level disadvantage and alcohol use disorder in northern Mexico.
AB  - BACKGROUND: In Mexico, the Northern States are highly impacted by alcohol
      consumption and associated problems. Little is known about the association
      between contextual social disadvantage and alcohol use disorder in this region.
      METHODS: Information from 1265 current drinkers surveyed in the U.S.-Mexico Study
      on Alcohol and Related Conditions (UMSARC) was combined with official data on
      neighborhood disadvantage (index of urban marginalization, a composite of ten
      indicators of area-level social disadvantage) for 302 neighborhoods. Using
      statistical marginal models, we estimated the association of neighborhood
      disadvantage with alcohol use disorder (AUD; based on DSM-5 criteria), alone and
      with adjustment for individual and contextual covariates. We also tested for
      moderation of neighborhood disadvantage effects by sex, education, internal
      migration and border area. RESULTS: There was a statistically significant
      increase in the odds of AUD of 59% (AOR=1.59; 95%CI=1.03, 2.46) for every one
      point increase on the neighborhood disadvantage scale, after adjustment for
      covariates. A significant interaction between sex and neighborhood disadvantage
      was indicated by two measures of additive interaction (AP=0.55; p<0.001 and
      S=2.55; p<0.001), with higher neighborhood disadvantage related to higher
      prevalence of AUD for men but not for women. No moderation effects were observed
      for education, internal migration or border area. CONCLUSIONS: Neighborhood
      disadvantage is a risk factor for AUD independent of other variables,
      specifically in men. Studies of contextual variables offer the possibility for
      understanding the role of collective circumstances on individuals in society.
      Future studies of alcohol use in this geographic area should consider effects of
      contextual determinants such as disadvantage.

PMID- 28456102
TI  - Enhanced electrical conductivity of collagen films through long-range aligned
      iron oxide nanoparticles.
AB  - The development of biocompatible collagen substrates able to conduct electric
      current along specific pathways represent an appealing issue in tissue
      engineering, since it is well known that electrical stimuli significantly affects
      important cell behaviour, such as proliferation, differentiation, directional
      migration, and, therefore, tissue regeneration. In this work, a cheap and easy
      approach was proposed to produce collagen-based films exhibiting enhanced
      electrical conductivity, through the simple manipulation of a weak external
      magnetic trigger. Paramagnetic iron oxide nanoparticles (NPs) capped by a
      biocompatible polyethylene-glycol coating were synthetized by a co-precipitation
      and solvothermic method and sprayed onto a collagen suspension. The system was
      then subjected to a static external magnetic field in order to conveniently tune
      NPs organization. Under the action of the external stimulus, NPs were induced to
      orient along the magnetic field lines, forming long-range aligned micropatterns
      within the collagen matrix. Drying of the substrate following water evaporation
      permanently blocked the magnetic architecture produced, thereby preserving NPs
      organization even after magnetic field removal. Electrical conductivity
      measurements clearly showed that the presence of such a magnetic framework
      endowed collagen with marked conductive properties in specific directions. The
      biocompatibility of the paramagnetic collagen films was also demonstrated by MTT
      cell cytotoxicity test.

PMID- 28456103
TI  - Formation of positively charged gold nanoparticle monolayers on silica sensors.
AB  - Formation of positively charged gold nanoparticle monolayers on the Si/SiO2 was
      studied under in situ conditions using quartz microbalance (QCM). The gold
      nanoparticles were synthesized in a chemical reduction method using sodium
      borohydride as reducing agent. Cysteamine hydrochloride was applied to generate a
      positive surface charge of nanoparticles. The micrographs obtained from
      transmission electron microscopy (TEM) revealed that the average size of
      nanoparticles was equal to 12+/-3nm. The stability of nanoparticle suspensions
      under controlled pH and ionic strength was determined by dynamic light scattering
      (DLS). The electrophoretic mobility measurements showed that the zeta potential
      of nanoparticles was positive, decreasing with ionic strength and pH from 56mV at
      pH 4.2 and I=10-4M to 22mV at pH 8.3 and I=3*10-3M. The surface enhanced Raman
      spectroscopy (SERS) confirmed chemisorption of cysteamine on nanoparticles and
      the contribution of amine moieties in the generation of nanoparticle charge. The
      influence of suspension concentration, ionic strength and flow rate on the
      kinetics of nanoparticle deposition on the sensors was quantitatively determined.
      It was confirmed that the deposition for the low coverage regime is governed by
      the bulk mass transfer that results in a linear increase of the coverage with
      time. The significant increase in the maximum coverage of gold monolayers with
      ionic strength was interpreted as due to the decreasing range of the
      electrostatic interactions among deposited particles. Moreover, the hydratation
      of formed monolayers, their structure and the stability were determined by the
      comparison of the QCM results with those obtained by AFM and SEM. The
      experimental data were adequately interpreted in terms of the extended random
      sequential adsorption (eRSA) model that considers the bulk and surface transfer
      steps in a rigorous way. The obtained results are useful for a facile fabrication
      of gold nanoparticle-based biosensors capable to bind target molecules via
      available amine moieties.

PMID- 28456104
TI  - Influence of bile salt on vitamin E derived vesicles involving a surface active
      ionic liquid and conventional cationic micelle.
AB  - This study has been actually performed with the aim to develop vitamin E derived
      vesicles individually from a surface active ionic liquid (1-Hexadecyl-3
      Methylimidazolium chloride ([C16mim]Cl)) and a common cationic amphiphile
      (benzyldimethylhexadecylammonium chloride (BHDC)) and also to investigate their
      consequent breakdown in presence of bile salt molecule. From this study, it is
      revealed that the rotational motion of coumarin 153 (C153) molecule is hindered
      as the vitamin E content is increased in the individual micellar solution of
      [C16mim]Cl and BHDC. The extent of enhancement in rotational relaxation time is
      more pronounced in case of [C16mim]Cl-vitamin E solutions than in the BHDC
      vitamin E vesicular aggregates which confirms the greater rigidity of the former
      vesicular system than the later one. Moreover, the effect of bile salt in the
      vitamin E forming vesicular assemblies have also been unravelled. It is found
      that the large area occupancy by the steroidal backbone of the bile salt plays a
      crucial role towards the enlargement of the average surfactant head group area.
      This results in disintegration of the vesicles composed of vitamin E and
      consequently, vesicles are transformed into mixed micellar aggregates. From the
      anisotropy measurement it is found that the rotational motion of C153 is more
      hindered in the [C16mim]Cl/BHDC-NaCh mixed micelles compared to that inside the
      individual vesicles. The fluorescence correlation spectroscopic (FCS) study also
      confirms that the mixed micelles have a more compact structure than that of the
      [C16mim]Cl-vitamin E and BHDC-vitamin E vesicles. Altogether, the micelle to
      vesicle transition involving any vitamin and their disruption by bile salt would
      be an interesting investigation both from the view point of basic colloidal
      chemistry and towards the generation of new drug delivery vehicle due to their
      unique microenvironment. Therefore, in future, these systems can be utilised as
      vehicle for the transport and as well as delivery of drugs and as probable
      reactor in nanomaterial synthesis.

PMID- 28456105
TI  - Dual-mode blue emission, enhanced up-conversion luminescence and paramagnetic
      properties of ytterbium and thulium-doped Ba2GdF7 multifunctional nanophosphors.
AB  - A series of Ba2GdF7:Yb3+, Tm3+ nanophosphors (NPs) with dual-mode (down
      conversion (DC) and upconversion (UC)) luminescence were successfully prepared by
      hydrothermal method at 180 degrees C. The NPs have sphere-like morphology and
      cubic structure. Under the excitation of ultraviolet 355nm and near-infrared
      980nm, Yb3+ and Tm3+ ions co-doped Ba2GdF7 phosphors exhibit bright blue dual
      mode emission. The mechanism of UC emissions was determined three-photon
      absorption. The energy transfer processes from Yb3+ to Tm3+ were discussed in
      detail. The up-conversion luminescence of Ba2GdF7:Yb3+/Tm3+ nanophosphors were
      enhanced by introducing the sensitizer Yb3+ ions and modifying the
      cetyltrimethylammonium bromide (CTAB) surfactant, respectively. Moreover, the as
      prepared samples exhibit paramagnetic properties at room temperature. This type
      of multifunctional nanophosphors have promising applications in anti
      counterfeiting, drug delivery, solid state lasers, biolabels, MRI, light emitting
      diodes (LEDs).

PMID- 28456106
TI  - Transparent and durable superhydrophobic coatings for anti-bioadhesion.
AB  - Although thousands of superhydrophobic coatings have been reported, transparent
      ones with high durability are rare. Here, transparent and durable
      superhydrophobic coatings were prepared by using multiwalled carbon nanotubes
      (MWCNTs) as the templates. The superhydrophobic coatings were prepared by spray
      coating the homogeneous suspension of polysiloxane-modified MWCNTs (MWCNTs@POS)
      in toluene onto glass slides, calcination in air at 500 degrees C to form the
      silica nanotubes (SNTs), and then chemical vapor deposition of
      polydimethylsiloxane at 200 degrees C onto the surface of the SNTs coatings. The
      MWCNTs@POS suspension was prepared by hydrolytic condensation of
      hexadecyltrimethoxysilane and tetraethoxysilane on the surface of MWCNTs. The
      coatings showed excellent superhydrophobicity (water contact angle=166.6 degrees
      , sliding angle=1 degrees ) and high transparency (83.1% at 600nm). In addition,
      the transparent superhydrophobic coatings featured high mechanical, chemical and
      thermal durability. The coatings retained the excellent superhydrophobicity after
      intensive water jetting at 100kPa for 60min, immersion in various corrosive
      liquids for 24h, or kept at 390 degrees C for 1h. Moreover, the transparent and
      durable superhydrophobic coatings exhibited very good anti-bioadhesive
      properties.

PMID- 28456107
TI  - Cobalt nanoparticles supported on N-doped mesoporous carbon as a highly efficient
      catalyst for the synthesis of aromatic amines.
AB  - Inexpensive and reusable transition metal heterogeneous catalysts exhibiting
      excellent catalytic performance represent an attractive alternative to noble
      metal and homogeneous catalysts. In this work, we fabricated a novel nanocatalyst
      comprised of Co nanoparticles (NPs) supported on a N-doped mesoporous carbon
      (Co/mCN-900) by simple one-pot pyrolysis of a homogeneous mixture of melamine,
      polyacrylonitrile, and Co(NO3)2.6H2O under a N2 atmosphere at 900 degrees C. The
      as-obtained Co/mCN-900 catalyst displayed a fluffy mesoporous structure with
      highly dispersed and accessible Co NPs acting as catalytic active sites. The
      Co/mCN-900 catalyst was effective in hydrogenating nitroarenes at milder
      conditions (i.e., 1MPa H2 and 120 degrees C) as compared to previously reported
      Co- and Ni-based catalysts. The Co/mCN-900 catalyst also catalyzed the reductive
      N-alkylation of nitroarenes with carbonyl compounds to form the corresponding
      aromatic secondary amines under very mild reaction conditions. In addition, the
      Co/mCN-900 catalyst showed good reusability since its morphology and activity
      were maintained after several reaction cycles. Therefore, this work provides a
      facile and promising method for fabricating non-precious transition metal-based
      catalysts with excellent performance and great potential for sustainable
      chemistry applications.

PMID- 28456109
TI  - Microbial population dynamics in urban organic waste anaerobic co-digestion with
      mixed sludge during a change in feedstock composition and different hydraulic
      retention times.
AB  - Microbial communities play an essential role in the biochemical pathways of
      anaerobic digestion processes. The correlations between microorganisms' relative
      abundance and anaerobic digestion process parameters were investigated, by
      considering the effect of different feedstock compositions and hydraulic
      retention times (HRTs). Shifts in microbial diversity and changes in microbial
      community richness were observed by changing feedstock composition from mono
      digestion of mixed sludge to co-digestion of food waste, grass clippings and
      garden waste with mixed sludge at HRT of 30, 20, 15 and 10 days. Syntrophic
      acetate oxidation along with hydrogenotrophic methanogenesis, mediated by
      Methanothermobacter, was found to be the most prevalent methane formation
      pathway, with the only exception of 10 days' HRT, in which Methanosarcina was the
      most dominant archaea. Significantly, the degradation of complex organic polymers
      was found to be the most active process, performed by members of S1
      (Thermotogales), Thermonema and Lactobacillus in a reactor fed with a high share
      of food waste. Conversely, Thermacetogenium, Anaerobaculum, Ruminococcaceae,
      Porphyromonadaceae and the lignocellulosic-degrading Clostridium were the
      significantly more abundant bacteria in the reactor fed with an increased share
      of lignocellulosic biomass in the form of grass clippings and garden waste.
      Finally, microbes belonging to Coprothermobacter, Syntrophomonas and Clostridium
      were correlated significantly with the specific methane yield obtained in both
      reactors.

PMID- 28456108
TI  - Psychometric evaluation of the short version of the Personal Diabetes
      Questionnaire to assess dietary behaviors and exercise in patients with type 2
      diabetes.
AB  - BACKGROUND: Patients with diabetes and of lower socioeconomic status have
      difficulty adhering to dietary recommendations. Practical and effective tools
      assessing self-management behaviors are needed to help evaluate interventions
      tailored to the needs of individual patients or population groups. This study
      examined the psychometric properties of a short 11-item version of the Personal
      Diabetes Questionnaire scale (PDQ-11) using data from the Public-Private
      Partnership to Improve Diabetes Education trial. METHODS: Patients (n=411) with
      type 2 diabetes from ten safety net primary care clinics in the Mid-Cumberland
      Region of Tennessee completed the PDQ-11, the Summary of Diabetes Self-Care
      Activities (SDSCA), the Perceived Diabetes Self-Management Scale (PDSMS), and the
      Adherence to Refills and Medications Scale (ARMS). Statistical analyses were
      conducted to explore the subscale structure of the PDQ-11, and the internal
      consistency and validity of its subscales. RESULTS: Exploratory factor analysis
      of the PDQ-11 revealed four components (Cronbach's alpha=0.50 to 0.81): Eating
      Behavior Problems; Use of Information for Dietary Decision Making; Calorie
      Restriction; and Activity and Exercise. Eating Behavior Problems and Use of
      Information for Dietary Decision Making had the strongest associations with the
      diet subscales of the SDSCA and were also correlated with the PDSMS and the ARMS
      scores (all ps<0.001). Different PDQ-11 subscales were correlated with BMI
      (Calorie Restriction Activity and Exercise) and blood pressure (Eating Behavior
      Problems). CONCLUSIONS: The PDQ-11 is a useful measure of dietary behaviors in
      patients with type 2 diabetes; its use may help providers tailor individual
      nutrition intervention strategies to patients.

PMID- 28456110
TI  - Quantitative assessment of energy and resource recovery in wastewater treatment
      plants based on plant-wide simulations.
AB  - The growing development of technologies and processes for resource treatment and
      recovery is offering endless possibilities for creating new plant-wide
      configurations or modifying existing ones. However, the configurations'
      complexity, the interrelation between technologies and the influent
      characteristics turn decision-making into a complex or unobvious process. In this
      frame, the Plant-Wide Modelling (PWM) library presented in this paper allows a
      thorough, comprehensive and refined analysis of different plant configurations
      that are basic aspects in decision-making from an energy and resource recovery
      perspective. In order to demonstrate the potential of the library and the need to
      run simulation analyses, this paper carries out a comparative analysis of WWTPs,
      from a techno-economic point of view. The selected layouts were (1) a
      conventional WWTP based on a modified version of the Benchmark Simulation Model
      No. 2, (2) an upgraded or retrofitted WWTP, and (3) a new Wastewater Resource
      Recovery Facilities (WRRF) concept denominated as C/N/P decoupling WWTP. The
      study was based on a preliminary analysis of the organic matter and nutrient
      energy use and recovery options, a comprehensive mass and energy flux
      distribution analysis in each configuration in order to compare and identify
      areas for improvement, and a cost analysis of each plant for different influent
      COD/TN/TP ratios. Analysing the plants from a standpoint of resources and energy
      utilization, a low utilization of the energy content of the components could be
      observed in all configurations. In the conventional plant, the COD used to
      produce biogas was around 29%, the upgraded plant was around 36%, and 34% in the
      C/N/P decoupling WWTP. With regard to the self-sufficiency of plants, achieving
      self-sufficiency was not possible in the conventional plant, in the upgraded
      plant it depended on the influent C/N ratio, and in the C/N/P decoupling WWTP
      layout self-sufficiency was feasible for almost all influents, especially at high
      COD concentrations. The plant layouts proposed in this paper are just a sample of
      the possibilities offered by current technologies. Even so, the library presented
      here is generic and can be used to construct any other plant layout, provided
      that a model is available.

PMID- 28456111
TI  - Valuable yet Vulnerable-A review of the challenges encountered by older nurses in
      the workplace.
AB  - OBJECTIVE: As the global nursing workforce ages, developing a comprehensive
      understanding of the experiences, needs and values specific to older nurses is
      increasingly significant. This paper reviews the evidence with regard to the
      specific challenges encountered by older nurses in the workplace. DESIGN: A
      scoping review of the published literature was conducted using the electronic
      databases Medline, CINAHL, PsycINFO, Science Direct and Google Scholar. A total
      of 20 papers were included in this review, most of which were qualitative (n=14).
      Three quantitative studies were identified (including one study which combined a
      physical exam with survey methods) as well as three mixed method studies.
      RESULTS: The challenges faced by older nurses in their practice are synthesised
      across three primary domains: Nursing and the ageing body; Recognition and
      support of the older nurse and Demands associated with middle-age. CONCLUSION: As
      older nurses form a substantial proportion of the healthcare workforce in many
      countries, the development and implementation of strategies to address these
      challenges is of utmost importance.

PMID- 28456112
TI  - Light sensing and responses in marine microalgae.
AB  - Marine eukaryotic phytoplankton are major contributors to global primary
      production. To adapt and thrive in the oceans, phytoplankton relies on a variety
      of light-regulated responses and light-acclimation capacities probably driven by
      sophisticated photoregulatory mechanisms. A plethora of photoreceptor-like
      sequences from marine microalgae have been identified in omics approaches.
      Initial studies have revealed that some algal photoreceptors are similar to those
      known in plants. In addition, new variants with different spectral tuning and
      algal-specific light sensors have also been found, changing current views and
      perspectives on how photoreceptor structure and function have diversified in
      phototrophs experiencing different environmental conditions.

PMID- 28456113
TI  - The enhancement mechanism of wine-processed Radix Scutellaria on NTG-induced
      migraine rats.
AB  - To elucidate the increasing dissolution and enhancement mechanism of wine
      processed Radix Scutellaria (RS) by fractal theory in nitroglycerin (NTG)-induced
      migraine rats. We prepared three RS from the process with 10% (S1), 15% (S2), 20%
      (S3) (v/m) rice wine. Mercury intrusion porosimetry and scanning electron
      microscope were employed to explore the internal structure of RS and the
      components dissolution of RS was analyzed by HPLC. Rats were randomly allocated
      into following groups and orally given different solutions for 10days: normal
      group (NOR, normal saline), model group (MOD, normal saline), Tianshu capsule
      group (TSC, 0.425mg/kg), ibuprofen group (IBU, 0.0821mg/kg), crude RS group (CRU,
      1.04mg/kg) and wine-processed RS group (WP, 1.04mg/kg) followed by bolus
      subcutaneously injection of NTG (10mg/kg) to induce migraine model except NOR.
      Biochemical indexes (nitric oxide-NO, calcitonin-gene-related peptide-CGRP, and
      endothelin-ET) and c-fos positive cells were measured with commercial kits and
      immunohistochemical method, separately. Total surface area significantly
      increased in wine-processed RS (p<0.05) while fractal dimension markedly
      decreased (p<0.05) compared with crude RS. Additionally, S3 owned the highest
      increase of dissolution including the percentage increase of total extract, total
      flavonoids and main compounds (all p<0.05 vs S1 and S2). Pharmacodynamic data
      showed c-fos positive cells significantly decreased (p<0.05) in WP compared with
      MOD and the level of NO, CGRP, ET in WP was better than that of CRU. Wine
      processed RS could be a promising candidate medicine for migraine treatment due
      to its increased component dissolution.

PMID- 28456114
TI  - Gene Expression Signature Differentiates Histology But Not Progression Status of
      Early-Stage NSCLC.
AB  - Advances in molecular analyses based on high-throughput technologies can
      contribute to a more accurate classification of non-small cell lung cancer
      (NSCLC), as well as a better prediction of both the disease course and the
      efficacy of targeted therapies. Here we set out to analyze whether global gene
      expression profiling performed in a group of early-stage NSCLC patients can
      contribute to classifying tumor subtypes and predicting the disease prognosis.
      Gene expression profiling was performed with the use of the microarray technology
      in a training set of 108 NSCLC samples. Subsequently, the recorded findings were
      validated further in an independent cohort of 44 samples. We demonstrated that
      the specific gene patterns differed significantly between lung adenocarcinoma
      (AC) and squamous cell lung carcinoma (SCC) samples. Furthermore, we developed
      and validated a novel 53-gene signature distinguishing SCC from AC with 93%
      accuracy. Evaluation of the classifier performance in the validation set showed
      that our predictor classified the AC patients with 100% sensitivity and 88%
      specificity. We revealed that gene expression patterns observed in the early
      stages of NSCLC may help elucidate the histological distinctions of tumors
      through identification of different gene-mediated biological processes involved
      in the pathogenesis of histologically distinct tumors. However, we showed here
      that the gene expression profiles did not provide additional value in predicting
      the progression status of the early-stage NSCLC. Nevertheless, the gene
      expression signature analysis enabled us to perform a reliable subclassification
      of NSCLC tumors, and it can therefore become a useful diagnostic tool for a more
      accurate selection of patients for targeted therapies.

PMID- 28456116
TI  - Influence of surface modified dental implant abutments on connective tissue
      attachment: A systematic review.
AB  - OBJECTIVE: Determine whether surface modified prosthetic abutments for dental
      implants influence connective tissue attachment to the implant-abutment system.
      DESIGN: A systematic review was conducted using the MEDLINE-PubMed database, with
      two independent reviewers filtering the titles and abstracts. Two reviewers
      assessed all potentially relevant articles. An assessment was carried out on the
      level of evidence of the research according to the guidelines of the Oxford
      Centre for Evidence-Based Medicine (OCEBM). RESULTS: After an initial search, 109
      potentially relevant articles were found. After reading the titles and abstracts,
      99 articles were excluded because the surface treatment was limited to the
      implant and not to the abutment, or because different materials were analysed
      instead of surface treatments; 28 were also duplicate articles. An additional 6
      research studies were included that were of interest and were found by reading
      the references of the included articles. The studies included are: 7 in vitro
      studies, 5 experimental studies in animals, 2 clinical trials in humans and 2
      clinical cases. CONCLUSION: Surface modification for prosthetic abutments on
      dental implants can achieve connective tissue attachment to the abutment;
      however, more studies should be conducted in humans to obtain more and better
      evidence of these results.

PMID- 28456115
TI  - Magnetic Resonance Imaging (MRI) of Intratumoral Voxel Heterogeneity as a
      Potential Response Biomarker: Assessment in a HER2+ Esophageal Adenocarcinoma
      Xenograft Following Trastuzumab and/or Cisplatin Therapy.
AB  - We evaluated magnetic resonance imaging (MRI) voxel heterogeneity following
      trastuzumab and/or cisplatin in a HER2+ esophageal xenograft (OE19) as a
      potential response biomarker. OE19 xenografts treated with saline (controls),
      monotherapy, or combined cisplatin and trastuzumab underwent 9.4-T MRI. Tumor MRI
      parametric maps of T1 relaxation time (pre/post contrast), T2 relaxation time,
      T2* relaxation rate (R2*), and apparent diffusion coefficient obtained before
      (TIME0), after 24hours (TIME1), and after 2weeks of treatment (TIME2) were
      analyzed. Voxel histogram and fractal parameters (from the whole tumor, rim and
      center, and as a ratio of rim-to-center) were derived. Tumors were stained for
      immunohistochemical markers of hypoxia (CA-IX), angiogenesis (CD34), and
      proliferation (Ki-67). Combination therapy reduced xenograft growth rate
      (relative change, ? +0.58+/-0.43 versus controls, ? +4.1+/-1.0; P=0.008). More
      spatially homogeneous voxel distribution between the rim to center was noted
      after treatment for combination therapy versus controls, respectively, for
      contrast-enhanced T1 relaxation time (90th percentile: ratio 1.00 versus 0.88,
      P=0.009), T2 relaxation time (mean: 1.00 versus 0.92, P=0.006; median: 0.98
      versus 0.91, P=0.006; 75th percentile: 1.02 versus 0.94, P=0.007), and R2* (10th
      percentile: 0.99 versus 1.26, P=0.003). We found that combination and trastuzumab
      monotherapy reduced MRI spatial heterogeneity and growth rate compared to the
      control or cisplatin groups, the former providing adjunctive tumor response
      information.

PMID- 28456117
TI  - Correlation of binding efficacies of DNA to flavonoids and their induced cellular
      damage.
AB  - Flavonoids are dietary intakes which are bestowed with several health benefits.
      The most studied property of flavonoids is their antioxidant efficacy. Among the
      chosen flavonoids Quercetin, Kaempferol and Myricetin is catagorized as flavonols
      whereas Apigenin and Luteolin belong to the flavone group. In the present study
      anti-cancer properties of flavonoids are investigated on the basis of their
      binding efficacy to ct-DNA and their ability to induce cytotoxicity in K562
      leukaemic cells. The binding affinities of the flavonoids with calf thymus DNA
      (ct-DNA) are in the order Quercetin>Myricetin>Luteolin>Kaempferol>Apigenin.
      Quercetin with fewer OH than myricetin has higher affinity towards DNA suggesting
      that the number and position of OH influence the binding efficacies of flavonoids
      to ct-DNA. CD spectra and EtBr displacement studies evidence myricetin and
      apigenin to be stronger intercalators of DNA compared to quercetin. From comet
      assay results it is observed that quercetin and myricetin when used in
      combination induce higher DNA damage in K562 leukemic cells than when tested
      individually. Higher binding efficacy has been recorded for quercetin to DNA at
      lower pH, which is the micro environment of cancerous cells, and hence quercetin
      can act as a potential anti-cancer agent. Presence of Cu also increases cellular
      damage as recorded by comet assay.

PMID- 28456118
TI  - DNA interaction, antimicrobial, anticancer activities and molecular docking study
      of some new VO(II), Cr(III), Mn(II) and Ni(II) mononuclear chelates encompassing
      quaridentate imine ligand.
AB  - The present study was conducted to synthesis of some new imine Cr(III), VO(II),
      Mn(II) and Ni(II) complexes derived from the condensation of 2-amino phenol with
      2-hydroxynapthaldehyde were synthesized. The prepared HNPN imine ligand was
      analyzed by its melting point, IR, 1H NMR and 13C NMR spectroscopies. The
      investigated HNPN imine complexes were characterized by elemental analysis, FT
      IR, UV-vis and thermal analysis (TGA) under nitrogen atmosphere from ambient
      temperature to 750 degrees C. The experimental results revealed that the
      investigated complexes contain hydrated water molecules. The molar conductance
      values of complexes are relatively low, indicating the non-electrolytic nature of
      these complexes. Magnetic susceptibility measurements show that the investigated
      complexes are paramagnetic. Moreover, the stability constants of the preparing
      complexes were determined spectrophotometrically. All the complexes were found to
      be monomeric 1:1 (M:L) stoichiometry in nature with octahedral geometry for
      Cr(III), tetrahedral for Mn(II), square planner for Ni(II) and square pyramidal
      for VO(II). Moreover, the prepared HNPN imine ligand and its complexes were
      evaluated for antimicrobial effect against some types of bacteria such as
      Bacillus subtilis (+ve), Escherichia coli(-ve) and Staphylococcus aureus (+ve)
      and some types of fungi such as Aspergillusniger, Candida glabrata and
      Trichophyton rubrum. The results of these studies indicate that the metal
      complexes exhibit a stronger antibacterial and antifungal efficiency compared to
      their corresponding imine ligand. Moreover, the interaction of the investigated
      complexes with CT-DNA was checked using spectral studies, viscosity measurements
      and gel electrophoreses. The absorption titration studies revealed that each of
      these complexes is an avid binder to calf thymus-DNA. Also, there was appreciable
      changes in the relative viscosity of DNA, which is consistent with enhanced
      hydrophobic interaction of the aromatic rings and intercalation mode of binding.
      In addition to, the cytotoxic activity of the prepared imine complexes on human
      colon carcinoma cells, (HCT-116 cell line), hepatic cellular carcinoma cells,
      (HepG-2 cell line) and breast carcinoma cells (MCF-7 cell line) has cytotoxicity
      effect against growth of carcinoma cells compared to the clinically used
      Vinblastine standard. Furthermore, the molecular docking into TRK (PDB: 1t46) was
      done for the optimization of the investigated compounds as potential TRK
      inhibitors.

PMID- 28456119
TI  - Theoretical insights on flavanones as antioxidants and UV filters: A TDDFT and
      NLMO study.
AB  - UV radiations can cause several irritations to the skin like sunburn, photo aging
      and even skin cancer. Sunscreens are widely used to protect the skin against
      these harmful radiations. One of the ingredients present in these sunscreens are
      organic molecules capable of absorbing these harmful radiations. Recently, the
      search is on for antioxidant molecules which can act as UV filters as they can
      facilitate photo protection. In this study, a computational investigation based
      on density functional theory (DFT) is attempted on flavanones namely pinocembrin,
      pinostrobin and alpinetin found in Boesenbergia pandurata. Several quantum
      chemical descriptors are computed to understand the antioxidant potentiality of
      these molecules. Quantum chemical descriptors of these flavanone molecules are
      found to be comparable to that of well-known anti-oxidant quercetin. UV response
      of these molecules are studied using time dependent density functional theory (TD
      DFT) formalism and by means of natural bond orbital (NBO) theory. It could be
      seen that these molecules exhibit a broad absorption in the UV region 270-390nm.
      This falls exactly in the region of harmful UVB and UVA radiation. Thus, these
      molecules have the potential to absorb the harmful UV radiation. From NLMO
      cluster studies, the orbital contribution to absorption is explained. In
      flavanones, unlike other classes of flavonoids, there is a discontinuity in the
      electron conjugation due to the absence of C2C3 double bond. This might be the
      key structural feature that leads to the absorption of these molecules to be
      centered around the UV region. These molecules can thus be treated as promising
      candidates for antioxidant UV filters in sunscreens.

PMID- 28456120
TI  - Distinct organ-specific and temporal expression profiles of auxin-related genes
      during mango fruitlet drop.
AB  - In mango, fruitlet abscission initiates with a decrease in polar auxin transport
      through the abscission zone (AZ), triggered by ethylene. To explore the molecular
      components affecting this process, we initially conducted experiments with
      developing fruitlet explants in which fruitlet drop was induced by ethephon, and
      monitored the expression patterns of distinct indole-3-acetic acid (IAA)-related
      genes, comparing control vs. ethephon-treated pericarp and AZ profiles. Over the
      examined time period (48 h), the accumulation of MiPIN1 and MiLAX2 IAA-efflux and
      influx genes decreased in both control and treated tissues. Nevertheless,
      ethephon-treated tissues displayed significantly lower levels of these
      transcripts within 18-24 h. An opposite pattern was observed for MiLAX3, which
      overall exhibited up-regulation in treated fruitlet tissues. Ethephon treatment
      also induced an early and pronounced down-regulation of five out of six IAA
      responsive genes, and a substantial reduction in the accumulation of two IAA
      synthesis related transcripts, contrasting with significant up-regulation of
      Gretchen Hagen3 transcript (MiGH3.1) encoding an IAA-amino synthetase.
      Furthermore, for both control and treated AZ, the decrease in IAA-carrier
      transcripts was associated with a decrease in IAA content and an increase in IAA
      Asp:IAA ratio, suggesting that fruitlet drop is accompanied by formation of this
      non-hydrolyzed IAA-amino acid conjugate. Despite these similarities, ethephon
      treated AZ displayed a sharper decrease in IAA content and higher IAA-Asp:IAA
      ratio within 18 h. Lastly, the response of IAA-related genes to exogenous IAA
      treatment was also examined. Our results are discussed, highlighting the roles
      that distinct IAA-related genes might assume during mango fruitlet drop.

PMID- 28456122
TI  - Effect of a dam on the optical properties of different-sized fractions of
      dissolved organic matter in a mid-subtropical drinking water source reservoir.
AB  - The presence of a dam on a river is believed to have a key role in affecting
      changes in the components of the chromophoric dissolved organic matter (CDOM) in
      reservoirs. However, questions remain about the mechanisms that control these
      changes. In this study, we used tangential ultrafiltration, fluorescence spectrum
      and phytoplankton cell density detection to explore the impacts of a dam on the
      CDOM components in the Shanzai Reservoir, a source of drinking water. The results
      demonstrated each CDOM size fraction comprised two main components, namely C1
      (protein-like substance) and C2 (humic-like substance). The C1 content had a
      higher value in areas with slow flow than in the normal river channel, while the
      C2 contents were generally stable in the flow direction. The topography of the
      reservoir site affected the structure of the CDOM components based on changes in
      the hydraulic conditions caused by the dam. The variations in the CDOM
      components, hydraulic parameters and fluorescence indices in the river flow
      direction indicated that the contribution of the phytoplankton to the CDOM
      content increased as the distance to the dam decreased, phytoplankton metabolism
      enhanced C1 content of the 1-10kDa molecular weights range fraction. Further, the
      contributions of different phytoplankton biomass to C1 proved that the dam
      changed the hydraulic conditions, had secondary effects on the metabolism of the
      phytoplankton, and resulted in changes in the structure of the CDOM components.

PMID- 28456121
TI  - Effects of root exudates on denitrifier gene abundance, community structure and
      activity in a micro-polluted constructed wetland.
AB  - In micro-polluted constructed wetland (CW), the low pollutant concentrations and
      the low COD/N ratios (chemical oxygen demand: total nitrogen in influent), make
      the biological treatment more difficult. It is expected that root exudates drive
      microbial-based transformations within plant rhizosphere. In this research, the
      roles of root exudates of three aquatic plants (Phragmites australis, Typha
      angustifolia and Cyperus alternifolius) in improving the growth of heterotrophic
      denitrifying bacteria were determined in a micro-polluted CW. In studied root
      rhizospheres, the total organic carbon (TOC) released from the plant roots varied
      significantly among plant species and seasons; the average TOC ranged from 0.1715
      to 0.9221mgg-1rootDMd-1, which could fuel a denitrification rate of approximately
      156-841kgNO3--Nha-1year-1 if all were used by the denitrifying bacteria; the
      abundances of nirK- and nirS-encoding bacteria were significantly influenced by
      the concentration of sucrose and glucose (0.869<=r<=0.933, p<0.05), and microbial
      community richness and diversity had response to root exudates. The results
      revealed that root exudates can act as endogenous carbon sources for
      heterotrophic denitrifying bacteria and ultimately determine the microbe
      distribution patterns in micro-polluted CW.

PMID- 28456123
TI  - Integrative biomarker assessment of the effects of chemically and mechanically
      dispersed crude oil in Pacific oysters, Crassostrea gigas.
AB  - The impact of dispersed crude oil and dispersant on adult Pacific oysters,
      Crassostrea gigas, was evaluated through an integrative biomarker approach
      including (1) biochemical (plasma catecholase- and laccase-type phenoloxidase and
      superoxide dismutase), (2) histological (digestive cell lysosomal responses,
      digestive gland histopathology) and (3) physiological (flesh condition index)
      endpoints in the haemolymph and digestive gland. Adult oysters were exposed to
      non-contaminated water (control), chemically-dispersed oil (Brut Arabian Light),
      mechanically-dispersed oil and dispersant (FINASOL(r)) alone for 2days, and
      further depurated in non-contaminated water for 4weeks. After exposure to
      chemically and mechanically dispersed oil oysters exhibited induction of plasma
      laccase-type phenoloxidase and superoxide dismutase activities, enlargement of
      digestive cell lysosomes, lipofuscin accumulation, reduced neutral lipid content
      and atrophy of digestive gland diverticula; more markedly on exposure to
      chemically dispersed oil. From the studied biomarkers, only lysosomal biomarkers
      were significantly affected after exposure to the dispersant alone. This included
      lysosomal enlargement, neutral lipid depletion and lipofuscin accumulation in the
      digestive gland epithelium. A recovery of plasma enzyme activities was observed
      after 4weeks of depuration. The integrative biological response index indicated
      that chemically dispersed oil caused significantly higher stress to C. gigas than
      the mechanically-dispersed one or the dispersant alone; nevertheless, the
      response seems to be reversible after depuration.

PMID- 28456124
TI  - Serum levels of organochlorine pesticides in blood donors: A biomonitoring survey
      in the North of Brazil, 2010-2011.
AB  - Data on exposure to organochlorine (OC) pesticides in the Brazilian population
      are lacking. The purpose of this study was to investigate the distribution of
      serum levels of OC pesticides in Brazilian blood donors and to determine factors
      potentially influencing exposure levels. To conduct this biomonitoring survey,
      blood samples were collected from blood donors attending the Hematherapic Unit in
      Rio Branco, North of Brazil, in 2010-2011. A total of 1183 (99%) subjects
      answered to a questionnaire including information on sociodemographics,
      lifestyle, and dietary habits. Twenty four OC pesticides were measured in serum
      samples from 978 donors (82%). Associations of OC pesticide serum levels and the
      number of OCs detected per donor with their potential predictors were explored by
      logistic and Poisson regression, respectively. Of the 24 OC pesticides analyzed,
      the highest prevalence was observed for p,p'-dichlorodiphenylethane (p,p'-DDE)
      (32%), followed by lindane (gamma-hexachlorocyclohexane) (20%), heptachlor (16%),
      and p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) (13%). 95th percentiles of
      levels of these four OC pesticides were: 3.85ng/mL (p,p'-DDE) (median<0.09ng/mL),
      0.09ng/mL (lindane) (median<0.04ng/mL), 0.23ng/mL (heptachlor)
      (median<0.09ng/mL), and 0.27ng/mL (p,p'-DDT) (median<0.02ng/mL). Factors
      significantly associated with a more frequent detection of OC pesticides included
      age, gender, education, and frequency of fish, manioc flour, acai pulp, and
      Brazil nuts intake. Major predictors of the number of OC pesticides detected were
      age, marital status, income, education, and frequency of consumption of manioc
      flour, acai pulp, and Brazil nuts. For the first time in Brazil, a biomonitoring
      study has assessed the internal doses of OC pesticides in a large sample of the
      adult population and potential exposure determinants. Except for lindane, which
      was permitted for use as a wood preservative until 2007 in Brazil, occurrence of
      OC pesticides was lower than or in the same range as those observed in other
      countries.

PMID- 28456125
TI  - Integrated approach of hydrological and water quality dynamic simulation for
      anthropogenic disturbance assessment in the Huai River Basin, China.
AB  - Detailed depiction of hydrological process and its associated pollution processes
      plays a critical role in environment improvement and management at basin scale.
      It also provides a useful tool to assess impact of potential factors on
      hydrological and water quality conditions. However, it was still difficult to
      well capture some typical characteristics of these complicated processes
      including built-in nonlinearity and time-variation, water infrastructure
      regulations, particularly for highly regulated basins. In this study, an
      integrated approach of hydrological and water quality dynamic simulation was
      proposed to solve these difficulties and assess the impacts of several
      anthropogenic disturbances. The Huai River Basin which was highly disturbed and
      seriously polluted, was selected as the study area. The main anthropogenic
      activities considered were point source pollution emissions, diffuse pollutant
      losses and dam regulations. Results showed that the integrated simulation could
      well capture the variations in water level, water discharge, concentrations of
      permanganate index (CODMn) and ammonia nitrogen (NH4-N) in high (2007), normal
      (2008) and low (2004) flow years at 15 stations in the upper and middle streams
      of Huai River Basin. The regulation rules of downstream sluices played negative
      roles on water quality improvement if keeping current pollution sources, while
      those of middle stream sluices played positive roles on water quality
      improvement. However, the water quality deterioration was mainly attributed to
      emission of point source pollution (12%-43%), followed by diffuse pollutant loss
      (0-23%) and water quantity-oriented dam regulation (-29%-20%). The study was
      expected to provide technical supports for the implementation of water pollution
      control and sustainable water resources management in the Huai River Basin, and
      give a reference of integrated hydrological and hydrodynamic simulation.

PMID- 28456126
TI  - Assessing the influence of the carbon source on the abatement of industrial N2O
      emissions coupled with the synthesis of added-value bioproducts.
AB  - The continuous abatement of a synthetic N2O emission from a nitric acid plant
      coupled with the simultaneously production of poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) copolymer and the coenzyme Q10 (CoQ10) in a bubble column
      reactor (BCR) was tested using methanol, glycerol and a mixture of sodium acetate
      acetic acid (Ac-HAc) as a carbon and electron donor source. The BCRs were
      inoculated with Paracoccus denitrificans and supplied with the carbon/electron
      donor at a loading rate of 139gCm-3d-1. High N2O removal efficiencies (81-91%)
      were achieved, with glycerol supporting the highest abatement. The PHBV cell
      content ranged from 25 to 53%, with highest accumulation in the culture obtained
      with methanol and Ac-HAc. However, the greatest PHBV productivities were observed
      in the BCRs operated with glycerol and Ac-HAc (21.7 and 33.5gPHBVm-3d-1,
      respectively). Glycerol supply induced the highest molar ratio (23%) of the
      homopolymer 3-hydroxyvalerate in the composition of PHBV. In addition, the
      specific cell content of CoQ10 ranged from 0.4 to 1mgg-1. This work constitutes,
      to the best of our knowledge, the first study combining N2O abatement with the
      simultaneous production of multiple bioproducts, which pave the way to the
      development of greenhouse gas biorefineries for climate change mitigation.

PMID- 28456127
TI  - Evidence of a sewer vapor transport pathway at the USEPA vapor intrusion research
      duplex.
AB  - The role of sewer lines as preferential pathways for vapor intrusion is poorly
      understood. Although the importance of sewer lines for volatile organic compound
      (VOC) transport has been documented at a small number of sites with vapor
      intrusion, sewer lines are not routinely sampled during most vapor intrusion
      investigations. We have used a tracer study and VOC concentration measurements to
      evaluate the role of the combined sanitary/storm sewer line in VOC transport at
      the USEPA vapor intrusion research duplex in Indianapolis, Indiana. The results
      from the tracer study demonstrated gas migration from the sewer main line into
      the duplex. The migration pathway appears to be complex and may include leakage
      from the sewer lateral at a location below the building foundation. Vapor samples
      collected from the sewer line demonstrated the presence of tetrachloroethene
      (PCE) and chloroform in the sewer main in front of the duplex and at multiple
      sample locations within the sewer line upstream of the duplex. These test results
      combined with results from the prior multi-year study of the duplex indicate that
      the sewer line plays an important role in transport of VOCs from the subsurface
      source to the immediate vicinity of the duplex building envelope.

PMID- 28456128
TI  - Natural herbicide activity of Satureja hortensis L. essential oil nanoemulsion on
      the seed germination and morphophysiological features of two important weed
      species.
AB  - The aim of the present study was to obtain an oil/water (O/W) nanoemulsion (NE)
      containing garden savory (Satureja hortensis) essential oil (EO) and evaluating
      its herbicidal activity against Amaranthus retroflexus and Chenopodium album. Gas
      chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were
      employed to determine the chemical composition of the EO. Carvacrol (55.6%) and
      gamma-terpinene (31.9%) were the major EO components. Low energy method was
      applied, allowing achievement of EO nanodroplets. The NE also presented low
      polydispersity, and the mean droplet was below 130nm even after storage for 30d.
      Laboratory tests showed that the NE at different concentrations (100, 200, 400,
      800, and 1000MUL.L-1) significantly (P<=0.05) reduced the germination indices and
      the seedling's growth in dose-response. The inhibitory effect was the greatest at
      800MUL.L-1 NE. Overall, root length was more inhibited as compared to shoot
      length. Post-emergence application of NE at different concentrations (1000, 2000,
      3000, 4000 and 5000MUL.L-1 of EO) on 2-4 true leaves' stage of the weeds caused
      significant (P<=0.05) decrease in the growth factors in dose-dependent manner.
      Complete lethality was observed by 4000MUL.L-1 NE sprayed on the weeds. Spraying
      of NE significantly (P<=0.05) reduced chlorophyll content in the tested weeds.
      Increasing in relative electrolyte leakage (REL) 1 and 5d after treatment
      represented significant cell membrane disruption and increased cell membrane
      permeability. Transmission electron microscope (TEM) pictures confirmed NE
      droplet size and demonstrated membrane destruction. The study approved that the
      NE of S. hortensis EO has herbicidal properties as it has high phytotoxic effect,
      and interferes with the germination, growth and physiological processes of the
      weeds. The production of NE from S. hortensis EO is a low energy method that
      offers a promising practical natural herbicide for weed control in organic
      agricultural systems.

PMID- 28456129
TI  - Ecological risk assessment of imidacloprid applied to experimental rice fields:
      Accurateness of the RICEWQ model and effects on ecosystem structure.
AB  - The fate of imidacloprid and its potential side-effects on biological communities
      and ecosystem functioning was studied in experimental rice plots. In addition,
      the influence of applying a withholding period of zero days (actual practices)
      and seven days (recommended in EU) on this was evaluated. Predicted environmental
      concentrations (PEC) of imidacloprid calculated with the higher-tier model RICEWQ
      agreed well with concentrations measured in the field. Methodologies generally
      used in the EU and USA for lower-tier PEC calculation, however, severely
      underestimated actual field concentrations and hence appear to need further
      evaluation and eventually amendments. Effects on several biological communities
      (especially ostracods, dipterans and coleopterans) were noted following
      imidacloprid application, with greatest effects in the paddy were as applied a
      withholding period of 7 days. An increase in the density of snails (Physa acuta),
      however, may have prevented effects on ecosystem functioning through functional
      redundancy. Implications of study findings for the ecological risk assessment of
      imidacloprid and potential mitigation measures are discussed.

PMID- 28456131
TI  - ED-SAFE-Can Suicide Risk Screening and Brief Intervention Initiated in the
      Emergency Department Save Lives?

PMID- 28456130
TI  - Suicide Prevention in an Emergency Department Population: The ED-SAFE Study.
AB  - Importance: Suicide is a leading cause of deaths in the United States. Although
      the emergency department (ED) is an opportune setting for initiating suicide
      prevention efforts, ED-initiated suicide prevention interventions remain
      underdeveloped. Objective: To determine whether an ED-initiated intervention
      reduces subsequent suicidal behavior. Design, Setting, and Participants: This
      multicenter study of 8 EDs in the United States enrolled adults with a recent
      suicide attempt or ideation and was composed of 3 sequential phases: (1) a
      treatment as usual (TAU) phase from August 2010 to December 2011, (2) a universal
      screening (screening) phase from September 2011 to December 2012, and (3) a
      universal screening plus intervention (intervention) phase from July 2012 to
      November 2013. Interventions: Screening consisted of universal suicide risk
      screening. The intervention phase consisted of universal screening plus an
      intervention, which included secondary suicide risk screening by the ED
      physician, discharge resources, and post-ED telephone calls focused on reducing
      suicide risk. Main Outcomes and Measures: The primary outcome was suicide
      attempts (nonfatal and fatal) over the 52-week follow-up period. The proportion
      and total number of attempts were analyzed. Results: A total of 1376 participants
      were recruited, including 769 females (55.9%) with a median (interquartile range)
      age of 37 (26-47) years. A total of 288 participants (20.9%) made at least 1
      suicide attempt, and there were 548 total suicide attempts among participants.
      There were no significant differences in risk reduction between the TAU and
      screening phases (23% vs 22%, respectively). However, compared with the TAU
      phase, patients in the intervention phase showed a 5% absolute reduction in
      suicide attempt risk (23% vs 18%), with a relative risk reduction of 20%.
      Participants in the intervention phase had 30% fewer total suicide attempts than
      participants in the TAU phase. Negative binomial regression analysis indicated
      that the participants in the intervention phase had significantly fewer total
      suicide attempts than participants in the TAU phase (incidence rate ratio, 0.72;
      95% CI, 0.52-1.00; P = .05) but no differences between the TAU and screening
      phases (incidence rate ratio, 1.00; 95% CI, 0.71-1.41; P = .99). Conclusions and
      Relevance: Among at-risk patients in the ED, a combination of brief interventions
      administered both during and after the ED visit decreased post-ED suicidal
      behavior.

PMID- 28456132
TI  - Response to: Routine usage of sentinel node biopsy in melanoma management must
      cease.

PMID- 28456134
TI  - Improvement in baroreflex control of renal sympathetic nerve activity in obese
      Sprague Dawley rats following immunosuppression.
AB  - AIM: This investigation explored the hypothesis that in obesity an inflammatory
      response in the kidney contributed to a renal nerve-dependent blunting of the
      baroreflex regulation of renal sympathetic nerve activity. METHODS: Rats received
      a normal (12% kcal) or high-fat (45% kcal) diet for 8 weeks plus daily injections
      of vehicle (0.9% NaCl i.p) or tacrolimus (0.25 mg kg-1 day-1 i.p) from weeks 3-8.
      Following anaesthesia, left renal sympathetic nerve activity was recorded,
      baroreflex gain curves were generated, by infusing phenylephrine and sodium
      nitroprusside, and cardiopulmonary baroreceptors challenged by infusing a saline
      load. RESULTS: The high-fat diet elevated weight gain and adiposity index by 89
      and 129% (both, P < 0.001). Mean blood pressure (132 +/- 4 vs 103 +/- 5 mmHg),
      fractional noradrenaline excretion and creatinine clearance (5.64 +/- 0.55 vs
      3.32 +/- 0.35 mL min-1 kg-1 ) were 28, 77 and 69% higher (all P < 0.05), but
      urine flow and fractional sodium excretions were 42 and 72% (both P < 0.001)
      lower compared to normal rats. Plasma and renal TNF-alpha and IL-6 concentrations
      were fourfold to fivefold (P < 0.001) and 22 and 20% higher (both, P < 0.05), in
      obese rats but normalized following tacrolimus. In obese rats, baroreflex
      sensitivity was reduced by 80% (P < 0.05) but restored by renal denervation or
      tacrolimus. Volume expansion reduced renal sympathetic nerve activity by 54% (P <
      0.001) in normal and obese rats subjected to renal denervation and tacrolimus,
      but not in obese rats with an intact renal innervation. CONCLUSION: Obesity
      induced a renal inflammation and pointed to this being both the origin of
      autonomic dysregulation and a potential focus for targeted therapy.

PMID- 28456133
TI  - Variants at the OCA2/HERC2 locus affect time to first cutaneous squamous cell
      carcinoma in solid organ transplant recipients collected using two different
      study designs.
AB  - BACKGROUND: Variants at the oculocutaneous albinism 2 (OCA2)/HECT and RLD domain
      containing E3 ubiquitin protein ligase 2 (HERC2) locus have been associated with
      pigmentation phenotypes and risk of developing several types of skin cancer.
      OBJECTIVES: To evaluate OCA2/HERC2 locus variants for their impact on time to
      develop cutaneous squamous cell carcinoma (cSCC) in organ transplant recipients
      (OTRs) who are at elevated risk of developing cSCC. METHODS: Participants were
      solid OTRs ascertained from two centres (n = 125 and 261) with an average of 13.1
      years of follow-up post-transplant. DNA was available for genotyping for all
      participants, in addition to medical records and questionnaire data. The Ohio
      State University study had a case-control design with prospective follow-up, and
      the University of California San Francisco study was a national cross-sectional
      survey with retrospective chart review. RESULTS: OCA2 variants rs12913832 and
      rs916977 were significantly associated with time to first cSCC post-transplant.
      OTRs homozygous for the brown-eye alleles of rs916977 (GG) and rs12913832 (AA)
      had significant delays of time to first cSCC post-transplant compared with
      individuals homozygous for the blue-eye alleles (hazard ratio 0.34, P < 0.001 and
      hazard ratio 0.54, P = 0.012, respectively). Both variants were highly associated
      with eye colour in the combined studies (P < 0.001). CONCLUSIONS: This study is
      the first to show an association between OCA2/HERC2 variants and time to first
      cSCC post-transplant. This may impact dermatological screening recommendations
      for high-risk populations.

PMID- 28456135
TI  - Differential characteristics and prognosis of patients with hepatitis B virus
      related acute-on-chronic liver failure defined by European Association for the
      Study of the Liver - Chronic Liver Failure criteria.
AB  - AIM: To determine the differential characteristics and prognosis of patients with
      hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) detected
      using Asian Pacific Association for the Study of the Liver (APASL) criteria and
      then classified using European Association for the Study of the Liver-Chronic
      Liver Failure (EASL-CLIF) criteria. METHODS: We retrospectively reviewed 316 HBV
      related APASL ACLF patients treated at Beijing 302 Hospital or Beijing You'An
      Hospital (both Beijing, China) between February 2015 and February 2016. Clinical
      characteristics and mortality rates were compared among patients with different
      EASL-CLIF ACLF severity grades (no ACLF, and ACLF grades 1-3). RESULTS: According
      to the EASL-CLIF criteria, 138 patients had no ACLF, 123 had ACLF at enrollment,
      and 55 developed ACLF during hospitalization. Both 28-day and 90-day transplant
      free mortality were dramatically lower in patients without EASL-CLIF ACLF (0.7%
      and 5.1%, respectively) than in patients with EASL-CLIF ACLF (40.7% and 63.2%,
      respectively; both P < 0.001). Liver failure rates were similar in patients with
      and without EASL-CLIF ACLF, but extrahepatic organ failure was rare in patients
      without EASL-CLIF ACLF. Baseline serum creatinine, new bacterial infection and
      new acute kidney injury during hospitalization, maximum rising rates of CLIF-C
      ACLF score, and Model for End-stage Liver Disease score were independent
      predictors of EASL-CLIF ACLF after enrollment. CONCLUSIONS: The EASL-CLIF ACLF
      classification can accurately prognosticate the short-term mortality of patients
      with HBV-related APASL ACLF. It can also distinguish distinct clinical
      characteristics and prognoses in patients with and without EASL-CLIF ACLF.

PMID- 28456136
TI  - A reply to: 'Impact of biologic therapies on risk of major adverse cardiovascular
      events in patients with psoriasis: systematic review and meta-analysis of
      randomized controlled trials'.

PMID- 28456137
TI  - The association of severe encephalopathy and question mark ear is highly
      suggestive of loss of MEF2C function.
AB  - Auriculocondylar syndrome and isolated question mark ear result from
      dysregulation of the endothelin 1-endothelin receptor type A signaling pathway.
      Animal models have highlighted the role of the transcription factor MEF2C as an
      effector of this pathway. We report heterozygous MEF2C loss-of-function as a
      possible cause of question mark ear associated with intellectual deficiency.

PMID- 28456138
TI  - Authors' response to a reply to: Re: Routine usage of sentinel node biopsy in
      melanoma management must cease.

PMID- 28456139
TI  - Visual outcomes of polypoidal choroidal vasculopathy treated with intravitreal
      ranibizumab with or without photodynamic therapy.

PMID- 28456140
TI  - Comparison of the rates of Clostridium difficile and bacteremia after delaying
      fluoroquinolone prophylaxis from day 0 to day +3 post autologous stem cell
      transplantation.
AB  - Prophylactic fluoroquinolones are routinely administered after stem cell
      transplantation (SCT) to prevent bacterial infection; however, fluoroquinolones
      may increase the risk of Clostridium difficile infection, particularly in
      immunocompromised patients. This study is designed to evaluate the effect of a
      delay by 3 days in fluoroquinolone prophylaxis after autologous SCT (ASCT) on the
      rates of C. difficile infection and bacteremia. A single-center retrospective
      cohort study was performed in 118 patients who received levofloxacin prophylaxis
      following ASCT at our institution between November 2014 and October 2015. In
      efforts to reduce the rate of C. difficile, initiation of levofloxacin
      prophylaxis was delayed from day 0 to day +3 of SCT beginning April 30, 2015. The
      incidence of C. difficile infection and of bacteremia in patients who initiated
      levofloxacin on day 0 was compared with those who started prophylaxis on day +3.
      We found no difference in the rates of C. difficile (7.9% vs 5.5%, P=.593) and
      bacteremia (7.9% vs 3.6%, P=.323) in patients who initiated levofloxacin on day 0
      compared with those who initiated prophylaxis on day +3. Delaying the initiation
      of levofloxacin prophylaxis by 3 days post ASCT showed no difference in the
      incidence of C. difficile or bacteremia. Future studies are warranted to show
      feasibility of delaying the initiation of antibiotic prophylaxis until
      neutropenia post ASCT, to further minimize the duration of antibiotic exposure.

PMID- 28456141
TI  - Relationship between the risk factors for human papillomavirus infection and
      lower genital tract precursor lesion and cancer development in female transplant
      recipients.
AB  - BACKGROUND: This study aimed to analyze the relationship between the several risk
      factors for human papillomavirus (HPV) infection and its persistence and to
      assess the prevalence of the lower genital tract precursor lesions, cancer, and
      HPV infection in female transplant recipients, besides the most prevalent HPV
      types. METHODS: The methodology adopted was a cross-sectional study with a random
      sample of 61 patients. RESULTS: The results indicated 10 cases (16.4%) of
      lesions, 54.5% of the overall prevalence of HPV infection, and HPV 16 was the
      most common high-risk HPV type, followed by HPV 51/53/70. A multiple logistic
      regression was done and hormone use presented a statistically significant
      association with high-risk HPV infection (P=.037). No statistically significant
      association was identified for the set of all factors with the lesions studied.
      CONCLUSIONS: The high prevalence of HPV infection and its precursor lesions
      confirmed the importance of differential screening and follow-up of transplanted
      patients. Condom use must be encouraged. The study result also confirmed the
      importance of knowledge of the viral type, in order to analyze the impact of HPV
      immunization, particularly against HPV types that are not 16/18. The reasonable
      rate of other genotypes, besides the vaccine types, should be considered to
      evaluate vaccination strategies.

PMID- 28456142
TI  - Endogenous glucocorticoids: role in the etiopathogenesis of Alzheimer's disease.
AB  - Endogenous glucocorticoids (eGCs) are steroid hormones with a wide spectrum of
      physiological effects. However, enhanced basal eGCs levels have been observed in
      patients affected by Alzheimer's disease (AD) and they have been correlated with
      dysregulation of the hypothalamic-pituitary-adrenocortical axis, hippocampal
      degeneration and reduced cognitive/memory performance. Therefore, it has been
      proposed that elevated concentration of eGCs might have a role in AD
      pathogenesis. AD is the most common form of dementia, characterized by the
      pathological accumulation of two proteins: the Amyloid Beta (Abeta) and the
      microtubule-associated protein tau in the neurons of the hippocampus and
      prefrontal cortex. In particular, the hippocampus, the cerebral area involved in
      learning and memory, is the brain region more vulnerable to chronic eGCs
      exposure. Although clinical studies have failed to establish a direct causative
      link between eGCs e and AD pathogenesis, evidences from pre-clinical studies have
      shown that increased eGCs levels accelerate the formation of Abeta in AD animal
      models by promoting the amyloidogenic pathway, and in parallel by reducing Abeta
      clearance, through transcriptional mechanisms involving the Glucocorticoid
      receptors. Instead, the effects of stress on tau phosphorylation seem to be
      mainly mediated bv the corticotropin-releasing factor receptor (CRFR1) and
      independent from stress-induced eGCs elevation.

PMID- 28456143
TI  - A first case of adrenomyeloneuropathy with mutation Y174S of the
      adrenoleukodystrophy gene.
AB  - The patient first noticed spasticity and weakness in his legs. He was diagnosed
      with chronic myelogenous leukemia (CML); the symptoms were attributed to
      neuropathy associated with CML. By treatment with dasatinib, he achieved complete
      hematological remission, but his difficulty in walking was not improved. His
      neurological symptom worsened together with an increase in body temperature and
      then disappeared together with a normalized body temperature, which may be
      attributed to the Uhthoff's phenomenon often observed in multiple sclerosis. He
      later developed acute fever, vomiting and a high adrenocorticotropic hormone
      (ACTH) level, which was diagnosed as adrenal insufficiency. Eventually, he was
      diagnosed with a milder form of adrenoleukodystrophy (ALD), adrenomyeloneuropathy
      (AMN) by increased levels of Very Long Chain Fatty Acids (VLCFAs) and genetic
      testing of the ATP binding cassette subfamily D member 1 (ABCD1) gene. A missense
      mutation (c.521A>C, p.Tyr174Ser), previously reported to induce severe cerebral
      ALD, was detected in exon1. Thus, clinical manifestation of ALD is determined by
      interaction between the primary ABCD1 mutation and modifying genetic and
      environmental factors. Physicians should be aware of the differing symptoms of
      AMN and determine the level of VLCFAs in patients having primary adrenal
      insufficiency, especially those complicated with neurological dysfunction. This
      is the first report of an AMN patient complicated with CML.

PMID- 28456144
TI  - Effects of venlafaxine and chronic unpredictable stress on behavior and
      hippocampal neurogenesis of rat dams.
AB  - OBJECTIVE: Epidemiological studies strongly support the theory that stressful
      life events play an important role in the etiology of depression. The mechanism
      of chronic stress induced depression involves a number of systems. Chronic stress
      represents a serious health issue especially during pregnancy and lactation. In
      this sensitive period, stress can lead to changes in emotion and cognitive
      behavior both of the mothers and the offspring. It is thus necessary to properly
      manage stress events during gestation. Venlafaxine belongs to the group of
      serotonin and noradrenaline re-uptake inhibitor drugs. It is used for the
      treatment of depression, anxiety disorders and other mood disorders. During
      pregnancy, however, the use of venlafaxine is questionable due to the lack of
      experimental and clinical studies. Therefore the aim of this study was to
      evaluate the effect of chronic unpredictable stress and/or venlafaxine treatment
      on maternal and open field behavior of dams. Moreover, hippocampal neurogenesis
      was investigated either. METHODS: Female Wistar rats were subjected to 2-week
      chronic unpredictable stress induced by random stressors and treated with
      venlafaxine orally at a dose of 5 mg/kg twice a day. Maternal behavior was
      evaluated within 5-min observations twice a day. Mothers were also tested in the
      open field 8 weeks after chronic unpredictable stress procedure in a single 15
      min session. Hippocampal neurogenesis was investigated by immunohistochemistry
      essay using DCX staining. RESULTS: Results of the present study showed altered
      maternal and open field behavior of the dams. Stressed dams had lowered
      hippocampal neurogenesis, while venlafaxine treatment reversed this lowering.
      CONCLUSIONS: These results suggest that stress and antidepressant therapy can
      have significant impact on behavior and hippocampal neurogenesis in rat dams.

PMID- 28456145
TI  - Autophagy plays beneficial effect on diabetic encephalopathy in type 2 diabetes:
      studies in vivo and in vitro.
AB  - OBJECTIVES: The hypothalamus regulates metabolism and feeding behavior by
      perceiving the levels of peripheral insulin. However, little is known about the
      hypothalamic changes after aberrant metabolism. In this study, we investigated
      the changes of insulin and autophagy relevant signals of hypothalamus under
      diabetes mellitus. METHODS: C57B/L mice were injected with low-dose
      streptozotocin (STZ) and fed with high-fat diet to induce type 2 diabetes
      mellitus. In vitro, PC12 cells were treated with oleic acid to mimic
      lipotoxicity. RESULTS: Results showed that the cholesterol level in the
      hypothalamus of the diabetic mice was higher than that of the normal mice. The
      expression of insulin receptors and insulin receptor substrate-1 were
      downregulated and the number of Fluoro-Jade C positive cells significantly
      increased in the hypothalamic arcuate nucleus of the diabetic mice. Furthermore,
      Upregulation of mammalian target of rapamycin (mTOR) and downregulation of LC 3II
      were obvious in the hypothalamus of the diabetic mice. In vitro, results showed
      that high-lipid caused PC12 cell damage and upregulated LC3 II expression.
      Pretreatment of cells with 3-methyladenine evidently downregulated LC3 II
      expression and aggravated PC12 cell death under high lipid conditions. By
      contrast, pretreatment of cells with rapamycin upregulated LC3 II expression and
      ameliorated PC12 cell death caused by lipotoxicity. CONCLUSION: These results
      demonstrate that autophagy activation confers protection to neurons under
      aberrant metabolism and that autophagy dysfunction in the hypothalamus occurs in
      the chronic metabolic disorder such as T2DM.

PMID- 28456146
TI  - Comparative effects of a fixed Polypodium leucotomos/Pomegranate combination
      versus Polypodium leucotomos alone on skin biophysical parameters.
AB  - OBJECTIVES: Polypodium leucotomos extract is a commonly used systemic
      photoprotective agent. In an exploratory fashion, the current study aimed to
      compare the effects of oral supplementation with a fixed Polypodium
      leucotomos/pomegranate combination (PPmix(r)) versus Polypodium leucotomos alone
      (Fernblock(r)) on skin biophysical parameters of Caucasian adults. METHODS: Forty
      healthy adult volunteers (20 males and 20 females; mean age: 37.2+/-5.5 years)
      were randomized in a 1:1 fashion to a fixed Polypodium leucotomos/pomegranate
      combination (480 mg/day; n=20) or Polypodium leucotomos alone (480 mg/day; n=20)
      for 3 months. Six skin biophysical parameters (skin sebum content, hydration,
      transepidermal water loss [TEWL], erythema index, melanin index, and elasticity)
      were measured at baseline and after 3 months by personnel blinded to participant
      allocation. RESULTS: At the end of the study, hydration and elasticity were
      significantly improved and TEWL was reduced in both groups, without significant
      intergroup differences. The erythema index was decreased by both treatments,
      although the fixed Polypodium leucotomos/pomegranate combination was
      significantly more effective. Finally, melanin index and skin sebum content were
      reduced by the fixed Polypodium leucotomos/pomegranate combination, whereas
      Polypodium leucotomos alone did not affect them. CONCLUSIONS: Our results suggest
      that a fixed Polypodium leucotomos/pomegranate combination provides a greater
      improvement of skin biophysical parameters compared to Polypodium leucotomos
      alone in adult Caucasians. Our findings may have implications for optimizing
      systemic skin photoprotection and beautification strategies.

PMID- 28456148
TI  - Impact of emotional disorders on semen quality in men treated for infertility.
AB  - OBJECTIVE: Semen quality depends on factors such as lifestyle, environment, and
      hormone secretion. OBJECTIVE: The purpose of the study was to assess the
      correlation between emotional disorders and the secretion of selected hormones,
      and to assess the impact of these disorders on semen quality. METHODS: The study
      covered 60 fertile and 112 subfertile males. The sperm was obtained by
      masturbation, and examined directly after liquidation according to the 2010
      criteria of the World Health Organization. The research instruments used were:
      the Beck Depression Inventory (BDI), and the State-Trait Anxiety Inventory
      (STAI). A morning blood sample (5 mL volume) was obtained and sent to an
      authorized laboratory to assess serum levels of testosterone, LH, FSH, prolactin,
      SHBG, DHEA-S and cortisol. RESULTS: In the group of infertility patients, higher
      BDI scores were correlated with significantly decreased testosterone levels
      (p=0.001), and increased prolactin and cortisol (p<0.001); statistically
      significant negative correlations were also found between BDI score and SHBG and
      DHEA-S (p<0.001) levels. Higher STAI-1 and STAI-2 in the low-fertility group were
      associated with higher mean prolactin and cortisol levels (p<0.001). Sperm count
      was shown to be correlated with BDI, STAI-1 and STAI-2 scores (p<0.001). Semen
      volume also correlated with BDI, STAI-1 and STAI-2 scores (p<0.001). CONCLUSION:
      Depression and anxiety in subfertile males are associated with lower secretion of
      SHBG and DHEA-S, and higher secretion of cortisol and prolactin. Depression and
      anxiety in male patients cause decreased semen volume and sperm density.

PMID- 28456147
TI  - Tyrosine hydroxylase gene expression is facilitated by alcohol followed by the
      degradation of the protein by ubiquitin proteasome system.
AB  - OBJECTIVES: Alcohol intake induces brief periods of euphoria; however, its
      continuous consumption can lead the development of alcohol tolerance. The
      euphoria, an intense feeling of wellbeing, is deeply associated with dopamine.
      Dopamine biosynthesis is strictly regulated by tyrosine hydroxylase (TH), a rate
      limiting enzyme of dopamine. The aim of this study was to examine the transient
      or chronic effects of ethanol treatment on TH protein level in vitro. METHODS:
      Cultured primary mesencephalic neurons were prepared and exposed to 100 mM
      ethanol for 48 hours or 168 hours. TH and cAMP-responsive element (CRE)-mediated
      transcriptional activity was measured by reporter gene assay using pTH9.0kb-Luc
      and pCRE-Luc reporter plasmid. TH protein expression and TH phosphorylation was
      analyzed by Western blot analysis. Dopamine content was measured by high
      performance liquid chromatography (HPLC). RESULTS: Ethanol treatment for 48 hours
      facilitates TH transcriptional activity and TH protein expression in a cAMP
      dependent protein kinase A (PKA) and MAPK/Erk kinase (MEK)-dependent manner in
      cultured mesencephalic neurons. Ethanol also facilitated TH phosphorylation,
      which resulted in the elevation of dopamine content. On the other hand, treatment
      with ethanol for 168 hours did not show significant elevation of TH gene
      expression and dopamine biosynthesis. Intriguingly, simultaneous treatment with
      MG-132, a 26S proteasomal inhibitor, recovered the ethanol-induced increase of TH
      protein expression and dopamine biosynthesis. CONCLUSION: Transient ethanol
      treatment facilitates TH gene expression and its phosphorylation in a PKA- and
      MEK-dependent manner to elevate dopamine biosynthesis, whereas continuous
      exposure to ethanol abolishes its potent effects on the dopaminergic function to
      reduce dopamine content. This reduction seems to originate from the decrease of
      TH protein level by degradation of the protein. Our current data may contribute
      to the better understanding of alcohol tolerance associated with degradation of
      TH protein to reduce total-TH level and dopamine biosynthesis.

PMID- 28456149
TI  - Plasma chemerin in young untrained men: association with cardio-metabolic traits
      and physical performance, and response to intensive interval training.
AB  - OBJECTIVES: Chemerin is an adipose tissue-derived adipokine thought to decrease
      insulin sensitivity and increase cardiometabolic risk. This study aimed to assess
      the association of chemerin with cardiometabolic risk and physical performance
      and examine its response to high-intensity interval training (HIIT). METHODS:
      Eighteen young men have been applied a HIIT program during 8 weeks. Plasma
      chemerin together with several cardiometabolic factors and physical performance
      indices were determined before and after the training program. Plasma chemerin
      and insulin were assessed using immunoenzymatic methods. The homeostasis model
      assessment (HOMA-IR) index was calculated as an estimate of insulin resistance.
      RESULTS: Basal plasma chemerin was positively correlated with body mass index
      (r=0.782, p<0.001), body fat (r=0.767, p<0.001), total (r=0.686, p=0.002) and LDL
      (r=0.587, p=0.010) cholesterol, triglycerides (r=0.775, p<0.001), HOMA-IR
      (r=0.673, p=0.002) and C-reactive protein (r=0.765, p<0.001). With regards to
      physical performance, chemerin was negatively correlated with maximal oxygen
      uptake (r=-0.572, p=0.013) and squat jump (r=-0.627, p=0.005), but positively
      related to 10-m sprint (r=0.716, p=0.001) and 30-m sprint (r=0.667, p=0.002)
      times. HIIT program resulted in significant improvements in body composition,
      plasma lipids and insulin sensitivity. However, no significant change was
      detected for plasma chemerin in response to HIIT (134+/-50.7 ng/mL vs. 137+/-51.9
      ng/mL, p=0.750). CONCLUSIONS: Basal plasma chemerin is associated with
      cardiometabolic health and physical performance in young men. Following HIIT,
      cardiometabolic health and physical performance had improved, but no significant
      change had occurred for plasma chemerin.

PMID- 28456150
TI  - Structural and construct validity of the Czech version of the Pittsburgh Sleep
      Quality Index in chronic insomnia.
AB  - OBJECTIVES: The Pittsburgh Sleep Quality Index (PSQI) is one of the widely used
      and recommended measures of assessing sleep quality in chronic insomnia; however
      certain psychometric properties of the questionnaire are still unknown in this
      group of patients. The present study aimed to examine the internal consistency,
      and structural and convergent validity of the Czech version of the PSQI in
      chronic insomnia patients. The usefulness of the standard and alternative scoring
      systems was also investigated in relation to symptoms of sleepiness, insomnia,
      depression, and anxiety. METHODS: In our study, 105 participants filled out a
      series of questionnaires including PSQI, Insomnia Severity Index (ISI), Epworth
      Sleepiness Scale (ESS), and Beck Depression and Anxiety Inventories (BDI, BAI).
      RESULTS: The internal consistency of the questionnaire using Cronbach's alpha was
      0.608. A series of confirmatory factor analyses revealed adequate fit for three
      structures. A three-factor model descriptively stood out among the rest but
      subsequent correlational analyses did not provide sufficient support for
      accepting an alternative scoring model. CONCLUSIONS: The results highlight the
      issue of structural variance of the PSQI and in chronic insomnia point to the
      important role of the PSQI components of daytime dysfunction and sleep
      disturbances in showing comorbid symptoms with daytime sleepiness and
      psychopathology.

PMID- 28456151
TI  - Cheap but accurate calculation of chemical reaction rate constants from ab initio
      data, via system-specific, black-box force fields.
AB  - Building on the recently published quantum-mechanically derived force field
      (QMDFF) and its empirical valence bond extension, EVB-QMDFF, it is now possible
      to generate a reliable potential energy surface for any given elementary reaction
      step in an essentially black box manner. This requires a limited and pre-defined
      set of reference data near the reaction path and generates an accurate
      approximation of the reference potential energy surface, on and off the reaction
      path. This intermediate representation can be used to generate reaction rate
      data, with far better accuracy and reliability than with traditional approaches
      based on transition state theory (TST) or variational extensions thereof (VTST),
      even if those include sophisticated tunneling corrections. However, the
      additional expense at the reference level remains very modest. We demonstrate all
      this for three arbitrarily chosen example reactions.

PMID- 28456152
TI  - Self-similarity and quasi-idempotence in neural networks and related dynamical
      systems.
AB  - Self-similarity across length scales is pervasively observed in natural systems.
      Here, we investigate topological self-similarity in complex networks representing
      diverse forms of connectivity in the brain and some related dynamical systems, by
      considering the correlation between edges directly connecting any two nodes in a
      network and indirect connection between the same via all triangles spanning the
      rest of the network. We note that this aspect of self-similarity, which is
      distinct from hierarchically nested connectivity (coarse-grain similarity), is
      closely related to idempotence of the matrix representing the graph. We introduce
      two measures, iota(1) and iota(infinity), which represent the element-wise
      correlation coefficients between the initial matrix and the ones obtained after
      squaring it once or infinitely many times, and term the matrices which yield
      large values of these parameters "quasi-idempotent". These measures delineate
      qualitatively different forms of "shallow" and "deep" quasi-idempotence, which
      are influenced by nodal strength heterogeneity. A high degree of quasi
      idempotence was observed for partially synchronized mean-field Kuramoto
      oscillators with noise, electronic chaotic oscillators, and cultures of
      dissociated neurons, wherein the expression of quasi-idempotence correlated
      strongly with network maturity. Quasi-idempotence was also detected for macro
      scale brain networks representing axonal connectivity, synchronization of slow
      activity fluctuations during idleness, and co-activation across experimental
      tasks, and preliminary data indicated that quasi-idempotence of structural
      connectivity may decrease with ageing. This initial study highlights that the
      form of network self-similarity indexed by quasi-idempotence is detectable in
      diverse dynamical systems, and draws attention to it as a possible basis for
      measures representing network "collectivity" and pattern formation.

PMID- 28456153
TI  - Dynamics of a class of fractional-order nonautonomous Lorenz-type systems.
AB  - The dynamical properties of a class of fractional-order Lorenz-type systems with
      quasi-periodic time-varying parameters are studied, where the fractional
      derivative is defined in the sense of Caputo. The effective non-integer dimension
      beta is the sum of all the fractional orders. Deferring from the fractional-order
      autonomous Lorenz systems, the present nonautonomous systems have two critical
      values, beta* and beta*, of the effective non-integer dimension, 0<beta*<beta*<3,
      under which there exist a transition from chaos to quasi-periodic dynamics for
      some beta near beta* and a transition from quasi-periodic motion to regular
      dynamics (diverging to infinity) for some beta near beta*. The 0-1 test is
      applied to verify the existence of such strange dynamics.

PMID- 28456154
TI  - Proof of the WARM whisker conjecture for neuronal connections.
AB  - This paper is devoted to the study of the so-called WARM reinforcement models
      that are generalisations of Polya's urn. We show that in the graph setting, once
      the exponent alpha of the reinforcement function is greater than 2, the stable
      and critical equilibria can be supported only on spanning forests, and once
      alpha>25, on spanning whisker forests. Thus, we prove the whisker forests
      conjecture from Hofstad et al. [Ann. Appl. Probab. 26(4), 2494-2539 (2016)].

PMID- 28456155
TI  - Optimal control of complex networks: Balancing accuracy and energy of the control
      action.
AB  - Recently, it has been shown that the control energy required to control a large
      dynamical complex network is prohibitively large when there are only a few
      control inputs. Most methods to reduce the control energy have focused on where,
      in the network, to place additional control inputs. We also have seen that by
      controlling the states of a subset of the nodes of a network, rather than the
      state of every node, the required energy to control a portion of the network can
      be reduced substantially. The energy requirements exponentially decay with the
      number of target nodes, suggesting that large networks can be controlled by a
      relatively small number of inputs as long as the target set is appropriately
      sized. Here, we see that the control energy can be reduced even more if the
      prescribed final states are not satisfied strictly. We introduce a new control
      strategy called balanced control for which we set our objective function as a
      convex combination of two competitive terms: (i) the distance between the output
      final states at a given final time and given prescribed states and (ii) the total
      control energy expenditure over the given time period. We also see that the
      required energy for the optimal balanced control problem approximates the
      required energy for the optimal target control problem when the coefficient of
      the second term is very small. We validate our conclusions in model and real
      networks regardless of system size, energy restrictions, state restrictions,
      input node choices, and target node choices.

PMID- 28456156
TI  - The remarkable coherence between two Italian far away recording stations points
      to a role of acoustic emissions from crustal rocks for earthquake analysis.
AB  - We observed a remarkable near-to-unity correlation between the time series of
      Acoustic Emissions (AEs) collected at two stations approximately 300 km apart
      from each other and located along the Apennine belt (Italy). This finding
      prompted us to verify the hypothesis that AE signals can carry with them an
      indication of anomalies in a crustal stress trend, possibly related to earthquake
      occurrences. Thus, we checked the ability of Recurrence Quantification Analysis
      and Fractal Analysis as applied to AE to identify signal phase transitions before
      the crisis occurs. The sharp drop of the Percent of Determinism after its maximum
      value, and simultaneously with minimum values of the Fractal Dimension (D), few
      days before some seismic events take place, seems to point to the relevance of
      the proposed approach as precursor detection.

PMID- 28456157
TI  - Detecting switching and intermittent causalities in time series.
AB  - During the last decade, complex network representations have emerged as a
      powerful instrument for describing the cross-talk between different brain regions
      both at rest and as subjects are carrying out cognitive tasks, in healthy brains
      and neurological pathologies. The transient nature of such cross-talk has
      nevertheless by and large been neglected, mainly due to the inherent limitations
      of some metrics, e.g., causality ones, which require a long time series in order
      to yield statistically significant results. Here, we present a methodology to
      account for intermittent causal coupling in neural activity, based on the
      identification of non-overlapping windows within the original time series in
      which the causality is strongest. The result is a less coarse-grained assessment
      of the time-varying properties of brain interactions, which can be used to create
      a high temporal resolution time-varying network. We apply the proposed
      methodology to the analysis of the brain activity of control subjects and
      alcoholic patients performing an image recognition task. Our results show that
      short-lived, intermittent, local-scale causality is better at discriminating both
      groups than global network metrics. These results highlight the importance of the
      transient nature of brain activity, at least under some pathological conditions.

PMID- 28456158
TI  - Multilayer motif analysis of brain networks.
AB  - In the last decade, network science has shed new light both on the structural
      (anatomical) and on the functional (correlations in the activity) connectivity
      among the different areas of the human brain. The analysis of brain networks has
      made possible to detect the central areas of a neural system and to identify its
      building blocks by looking at overabundant small subgraphs, known as motifs.
      However, network analysis of the brain has so far mainly focused on anatomical
      and functional networks as separate entities. The recently developed mathematical
      framework of multi-layer networks allows us to perform an analysis of the human
      brain where the structural and functional layers are considered together. In this
      work, we describe how to classify the subgraphs of a multiplex network, and we
      extend the motif analysis to networks with an arbitrary number of layers. We then
      extract multi-layer motifs in brain networks of healthy subjects by considering
      networks with two layers, anatomical and functional, respectively, obtained from
      diffusion and functional magnetic resonance imaging. Results indicate that
      subgraphs in which the presence of a physical connection between brain areas
      (links at the structural layer) coexists with a non-trivial positive correlation
      in their activities are statistically overabundant. Finally, we investigate the
      existence of a reinforcement mechanism between the two layers by looking at how
      the probability to find a link in one layer depends on the intensity of the
      connection in the other one. Showing that functional connectivity is non
      trivially constrained by the underlying anatomical network, our work contributes
      to a better understanding of the interplay between the structure and function in
      the human brain.

PMID- 28456159
TI  - Ising model with conserved magnetization on the human connectome: Implications on
      the relation structure-function in wakefulness and anesthesia.
AB  - Dynamical models implemented on the large scale architecture of the human brain
      may shed light on how a function arises from the underlying structure. This is
      the case notably for simple abstract models, such as the Ising model. We compare
      the spin correlations of the Ising model and the empirical functional brain
      correlations, both at the single link level and at the modular level, and show
      that their match increases at the modular level in anesthesia, in line with
      recent results and theories. Moreover, we show that at the peak of the specific
      heat (the critical state), the spin correlations are minimally shaped by the
      underlying structural network, explaining how the best match between the
      structure and function is obtained at the onset of criticality, as previously
      observed. These findings confirm that brain dynamics under anesthesia shows a
      departure from criticality and could open the way to novel perspectives when the
      conserved magnetization is interpreted in terms of a homeostatic principle
      imposed to neural activity.

PMID- 28456160
TI  - How structure sculpts function: Unveiling the contribution of anatomical
      connectivity to the brain's spontaneous correlation structure.
AB  - Intrinsic brain activity is characterized by highly organized co-activations
      between different regions, forming clustered spatial patterns referred to as
      resting-state networks. The observed co-activation patterns are sustained by the
      intricate fabric of millions of interconnected neurons constituting the brain's
      wiring diagram. However, as for other real networks, the relationship between the
      connectional structure and the emergent collective dynamics still evades complete
      understanding. Here, we show that it is possible to estimate the expected pair
      wise correlations that a network tends to generate thanks to the underlying path
      structure. We start from the assumption that in order for two nodes to exhibit
      correlated activity, they must be exposed to similar input patterns from the
      entire network. We then acknowledge that information rarely spreads only along a
      unique route but rather travels along all possible paths. In real networks, the
      strength of local perturbations tends to decay as they propagate away from the
      sources, leading to a progressive attenuation of the original information content
      and, thus, of their influence. Accordingly, we define a novel graph measure,
      topological similarity, which quantifies the propensity of two nodes to
      dynamically correlate as a function of the resemblance of the overall influences
      they are expected to receive due to the underlying structure of the network.
      Applied to the human brain, we find that the similarity of whole-network inputs,
      estimated from the topology of the anatomical connectome, plays an important role
      in sculpting the backbone pattern of time-average correlations observed at rest.

PMID- 28456161
TI  - Balance of excitation and inhibition determines 1/f power spectrum in neuronal
      networks.
AB  - The 1/f-like decay observed in the power spectrum of electro-physiological
      signals, along with scale-free statistics of the so-called neuronal avalanches,
      constitutes evidence of criticality in neuronal systems. Recent in vitro studies
      have shown that avalanche dynamics at criticality corresponds to some specific
      balance of excitation and inhibition, thus suggesting that this is a basic
      feature of the critical state of neuronal networks. In particular, a lack of
      inhibition significantly alters the temporal structure of the spontaneous
      avalanche activity and leads to an anomalous abundance of large avalanches. Here,
      we study the relationship between network inhibition and the scaling exponent
      beta of the power spectral density (PSD) of avalanche activity in a neuronal
      network model inspired in Self-Organized Criticality. We find that this scaling
      exponent depends on the percentage of inhibitory synapses and tends to the value
      beta = 1 for a percentage of about 30%. More specifically, beta is close to 2,
      namely, Brownian noise, for purely excitatory networks and decreases towards
      values in the interval [1, 1.4] as the percentage of inhibitory synapses ranges
      between 20% and 30%, in agreement with experimental findings. These results
      indicate that the level of inhibition affects the frequency spectrum of resting
      brain activity and suggest the analysis of the PSD scaling behavior as a possible
      tool to study pathological conditions.

PMID- 28456162
TI  - Long-term variability of importance of brain regions in evolving epileptic brain
      networks.
AB  - We investigate the temporal and spatial variability of the importance of brain
      regions in evolving epileptic brain networks. We construct these networks from
      multiday, multichannel electroencephalographic data recorded from 17 epilepsy
      patients and use centrality indices to assess the importance of brain regions.
      Time-resolved indications of highest importance fluctuate over time to a greater
      or lesser extent, however, with some periodic temporal structure that can mostly
      be attributed to phenomena unrelated to the disease. In contrast, relevant
      aspects of the epileptic process contribute only marginally. Indications of
      highest importance also exhibit pronounced alternations between various brain
      regions that are of relevance for studies aiming at an improved understanding of
      the epileptic process with graph-theoretical approaches. Nonetheless, these
      findings may guide new developments for individualized diagnosis, treatment, and
      control.

PMID- 28456163
TI  - Varieties of reentrant dynamics.
AB  - Experiments were carried out in monolayer tissue cultures of embryonic chick
      heart cells imaged using a calcium sensitive fluorescent dye. The cells were
      grown in annular geometries and in annular geometries with an isthmus connecting
      antipodal region of the annulus. We observed a large number of spatially
      different patterns of propagation consisting of one or more circulating waves. As
      well, we also observed rhythms in which rotors embedded in the annuli generated
      propagating pulses. These results demonstrate that many different patterns of
      excitation can be present in cardiac tissue with simple geometries.

PMID- 28456164
TI  - Front tracking for quantifying advection-reaction-diffusion.
AB  - We present an algorithm for measuring the speed and thickness of reaction fronts,
      and from those quantities, the diffusivity and the reaction rate of the active
      chemical species. This front-tracking algorithm provides local measurements
      suitable for statistics and requires only a sequence of concentration fields.
      Though our eventual goal is front tracking in advection-reaction-diffusion, here
      we demonstrate the algorithm in reaction-diffusion. We test the algorithm with
      validation data in which front speed and thickness are prescribed, as well as
      simulation results in which diffusivity and reaction rate are prescribed. In all
      tests, measurements closely match true values. We apply the algorithm to
      laboratory experiments using the Belousov-Zhabotinsky reaction, producing speed,
      diffusivity, and reaction rate measurements that are statistically more robust
      than in prior studies. Finally, we use thickness measurements to quantify the
      concentration profile of chemical waves in the reaction.

PMID- 28456165
TI  - Localized shear generates three-dimensional transport.
AB  - Understanding the mechanisms that control three-dimensional (3D) fluid transport
      is central to many processes, including mixing, chemical reaction, and biological
      activity. Here a novel mechanism for 3D transport is uncovered where fluid
      particles are kicked between streamlines near a localized shear, which occurs in
      many flows and materials. This results in 3D transport similar to Resonance
      Induced Dispersion (RID); however, this new mechanism is more rapid and mutually
      incompatible with RID. We explore its governing impact with both an abstract 2
      action flow and a model fluid flow. We show that transitions from one-dimensional
      (1D) to two-dimensional (2D) and 2D to 3D transport occur based on the relative
      magnitudes of streamline jumps in two transverse directions.

PMID- 28456166
TI  - Modular topology emerges from plasticity in a minimalistic excitable network
      model.
AB  - Topological features play a major role in the emergence of complex brain network
      dynamics underlying brain function. Specific topological properties of brain
      networks, such as their modular organization, have been widely studied in recent
      years and shown to be ubiquitous across spatial scales and species. However, the
      mechanisms underlying the generation and maintenance of such features are still
      unclear. Using a minimalistic network model with excitable nodes and discrete
      deterministic dynamics, we studied the effects of a local Hebbian plasticity rule
      on global network topology. We found that, despite the simple model set-up, the
      plasticity rule was able to reorganize the global network topology into a modular
      structure. The structural reorganization was accompanied by enhanced correlations
      between structural and functional connectivity, and the final network
      organization reflected features of the dynamical model. These findings
      demonstrate the potential of simple plasticity rules for structuring the topology
      of brain connectivity.

PMID- 28456167
TI  - Persistent homology of time-dependent functional networks constructed from
      coupled time series.
AB  - We use topological data analysis to study "functional networks" that we construct
      from time-series data from both experimental and synthetic sources. We use
      persistent homology with a weight rank clique filtration to gain insights into
      these functional networks, and we use persistence landscapes to interpret our
      results. Our first example uses time-series output from networks of coupled
      Kuramoto oscillators. Our second example consists of biological data in the form
      of functional magnetic resonance imaging data that were acquired from human
      subjects during a simple motor-learning task in which subjects were monitored for
      three days during a five-day period. With these examples, we demonstrate that (1)
      using persistent homology to study functional networks provides fascinating
      insights into their properties and (2) the position of the features in a
      filtration can sometimes play a more vital role than persistence in the
      interpretation of topological features, even though conventionally the latter is
      used to distinguish between signal and noise. We find that persistent homology
      can detect differences in synchronization patterns in our data sets over time,
      giving insight both on changes in community structure in the networks and on
      increased synchronization between brain regions that form loops in a functional
      network during motor learning. For the motor-learning data, persistence
      landscapes also reveal that on average the majority of changes in the network
      loops take place on the second of the three days of the learning process.

PMID- 28456168
TI  - Network structure of turbulent premixed flames.
AB  - In this paper, a generalized description of the complex topology of turbulent
      premixed flames stabilized in a model gas turbine combustor is obtained using
      network analysis. Networks are created using the visibility algorithm applied to
      points on the flame edge obtained from Hydroxyl radical (OH)-Planar Laser Induced
      Fluorescence images of turbulent premixed flames. The network structure thus
      obtained showed the emergence of a few massively connected nodes which were found
      to represent the folded regions of the flame front. These nodes, which are called
      the hubs of the network, are vital for determining the overall structure of the
      flame front. Degree distribution of the formulated networks is used to
      characterize the flame-turbulence interaction inherent in the system. Turbulent
      flame front networks were found to be rigid enough to be unaffected by random
      perturbations but highly vulnerable towards coordinated removal of hubs or folds.
      These findings could serve as the first network-analytic approach to characterize
      turbulence-flame interaction dynamics with the use of a flourishing network
      theory, which enhances ongoing works based on vortex dynamics, hydrodynamic
      stability, and thermo-acoustic instability.

PMID- 28456169
TI  - Reservoir observers: Model-free inference of unmeasured variables in chaotic
      systems.
AB  - Deducing the state of a dynamical system as a function of time from a limited
      number of concurrent system state measurements is an important problem of great
      practical utility. A scheme that accomplishes this is called an "observer." We
      consider the case in which a model of the system is unavailable or insufficiently
      accurate, but "training" time series data of the desired state variables are
      available for a short period of time, and a limited number of other system
      variables are continually measured. We propose a solution to this problem using
      networks of neuron-like units known as "reservoir computers." The measurements
      that are continually available are input to the network, which is trained with
      the limited-time data to output estimates of the desired state variables. We
      demonstrate our method, which we call a "reservoir observer," using the Rossler
      system, the Lorenz system, and the spatiotemporally chaotic Kuramoto-Sivashinsky
      equation. Subject to the condition of observability (i.e., whether it is in
      principle possible, by any means, to infer the desired unmeasured variables from
      the measured variables), we show that the reservoir observer can be a very
      effective and versatile tool for robustly reconstructing unmeasured dynamical
      system variables.

PMID- 28456170
TI  - Interplay of delay and multiplexing: Impact on cluster synchronization.
AB  - Communication delays and multiplexing are ubiquitous features of real-world
      network systems. We here introduce a simple model where these two features are
      simultaneously present and report the rich phenomenology which is actually due to
      their interplay on cluster synchronization. A delay in one layer has non trivial
      impacts on the collective dynamics of the other layers, enhancing or suppressing
      synchronization. At the same time, multiplexing may also enhance cluster
      synchronization of delayed layers. We elucidate several nontrivial (and anti
      intuitive) scenarios, which are of interest and potential application in various
      real-world systems, where the introduction of a delay may render synchronization
      of a layer robust against changes in the properties of the other layers.

PMID- 28456171
TI  - On the role of the entorhinal cortex in the effective connectivity of the
      hippocampal formation.
AB  - Inferring effective connectivity from neurophysiological data is a challenging
      task. In particular, only a finite (and usually small) number of sites are
      simultaneously recorded, while the response of one of these sites can be
      influenced by other sites that are not being recorded. In the hippocampal
      formation, for instance, the connections between areas CA1-CA3, the dentate gyrus
      (DG), and the entorhinal cortex (EC) are well established. However, little is
      known about the relations within the EC layers, which might strongly affect the
      resulting effective connectivity estimations. In this work, we build
      excitatory/inhibitory neuronal populations representing the four areas CA1, CA3,
      the DG, and the EC and fix their connectivities. We model the EC by three layers
      (LII, LIII, and LV) and assume any possible connection between them. Our results,
      based on Granger Causality (GC) and Partial Transfer Entropy (PTE) measurements,
      reveal that the estimation of effective connectivity in the hippocampus strongly
      depends on the connectivities between EC layers. Moreover, we find, for certain
      EC configurations, very different results when comparing GC and PTE measurements.
      We further demonstrate that causal links can be robustly inferred regardless of
      the excitatory or inhibitory nature of the connection, adding complexity to their
      interpretation. Overall, our work highlights the importance of a careful analysis
      of the connectivity methods to prevent unrealistic conclusions when only partial
      information about the experimental system is available, as usually happens in
      brain networks. Our results suggest that the combination of causality measures
      with neuronal modeling based on precise neuroanatomical tracing may provide a
      powerful framework to disambiguate causal interactions in the brain.

PMID- 28456172
TI  - Structural connectome topology relates to regional BOLD signal dynamics in the
      mouse brain.
AB  - Brain dynamics are thought to unfold on a network determined by the pattern of
      axonal connections linking pairs of neuronal elements; the so-called connectome.
      Prior work has indicated that structural brain connectivity constrains pairwise
      correlations of brain dynamics ("functional connectivity"), but it is not known
      whether inter-regional axonal connectivity is related to the intrinsic dynamics
      of individual brain areas. Here we investigate this relationship using a
      weighted, directed mesoscale mouse connectome from the Allen Mouse Brain
      Connectivity Atlas and resting state functional MRI (rs-fMRI) time-series data
      measured in 184 brain regions in eighteen anesthetized mice. For each brain
      region, we measured degree, betweenness, and clustering coefficient from weighted
      and unweighted, and directed and undirected versions of the connectome. We then
      characterized the univariate rs-fMRI dynamics in each brain region by computing
      6930 time-series properties using the time-series analysis toolbox, hctsa. After
      correcting for regional volume variations, strong and robust correlations between
      structural connectivity properties and rs-fMRI dynamics were found only when edge
      weights were accounted for, and were associated with variations in the
      autocorrelation properties of the rs-fMRI signal. The strongest relationships
      were found for weighted in-degree, which was positively correlated to the
      autocorrelation of fMRI time series at time lag tau = 34 s (partial Spearman
      correlation rho=0.58), as well as a range of related measures such as relative
      high frequency power (f > 0.4 Hz: rho=-0.43). Our results indicate that the
      topology of inter-regional axonal connections of the mouse brain is closely
      related to intrinsic, spontaneous dynamics such that regions with a greater
      aggregate strength of incoming projections display longer timescales of activity
      fluctuations.

PMID- 28456173
TI  - Vector semirational rogue waves and modulation instability for the coupled higher
      order nonlinear Schrodinger equations in the birefringent optical fibers.
AB  - We report the existence and properties of vector breather and semirational rogue
      wave solutions for the coupled higher-order nonlinear Schrodinger equations,
      which describe the propagation of ultrashort optical pulses in birefringent
      optical fibers. Analytic vector breather and semirational rogue-wave solutions
      are obtained with Darboux dressing transformation. We observe that the
      superposition of the dark and bright contributions in each of the two wave
      components can give rise to complicated breather and semirational rogue-wave
      dynamics. We show that the bright-dark type vector solitons (or breather-like
      vector solitons) with nonconstant speed interplay with Akhmediev breathers,
      Kuznetsov-Ma solitons, and rogue waves. By adjusting parameters, we note that the
      rogue wave and bright-dark soliton merge, generating the boomeron-type bright
      dark solitons. We prove that the rogue wave can be excited in the baseband
      modulation instability regime. These results may provide evidence of the
      collision between the mixed ultrashort soliton and rogue wave.

PMID- 28456174
TI  - Discrete rational and breather solution in the spatial discrete complex modified
      Korteweg-de Vries equation and continuous counterparts.
AB  - In this paper, a spatial discrete complex modified Korteweg-de Vries equation is
      investigated. The Lax pair, conservation laws, Darboux transformations, and
      breather and rational wave solutions to the semi-discrete system are presented.
      The distinguished feature of the model is that the discrete rational solution can
      possess new W-shape rational periodic-solitary waves that were not reported
      before. In addition, the first-order rogue waves reach peak amplitudes which are
      at least three times of the background amplitude, whereas their continuous
      counterparts are exactly three times the constant background. Finally, the
      integrability of the discrete system, including Lax pair, conservation laws,
      Darboux transformations, and explicit solutions, yields the counterparts of the
      continuous system in the continuum limit.

PMID- 28456175
TI  - Avalanche and edge-of-chaos criticality do not necessarily co-occur in neural
      networks.
AB  - There are indications that for optimizing neural computation, neural networks may
      operate at criticality. Previous approaches have used distinct fingerprints of
      criticality, leaving open the question whether the different notions would
      necessarily reflect different aspects of one and the same instance of
      criticality, or whether they could potentially refer to distinct instances of
      criticality. In this work, we choose avalanche criticality and edge-of-chaos
      criticality and demonstrate for a recurrent spiking neural network that avalanche
      criticality does not necessarily entrain dynamical edge-of-chaos criticality.
      This suggests that the different fingerprints may pertain to distinct phenomena.

PMID- 28456176
TI  - On-off intermittency in coupled chaotic thermoacoustic oscillations.
AB  - This paper documents on-off intermittency observed in coupled thermoacoustic
      chaotic oscillations. Mode competition between two or three oscillation modes
      engenders chaotic oscillations through quasiperiodic oscillations introduced by a
      local cross-sectional change in a gas-filled tube. Complete synchronization is
      then obtained by connecting two thermoacoustic chaotic oscillators via a rigid
      plate with an orifice. From the analysis of pressure fluctuations, theoretical
      statistical scaling laws related to the laminar phases, spectral density, and
      amplitude probability distribution are found to be satisfied in the coupled
      thermoacoustic oscillators, when the thermoacoustic complete synchronization
      breaks down through an on-off intermittency route with the decreased orifice
      size.

PMID- 28456177
TI  - Editorial: On the relation of dynamics and structure in brain networks.

PMID- 28456178
TI  - Linear and nonlinear stability of periodic orbits in annular billiards.
AB  - An annular billiard is a dynamical system in which a particle moves freely in a
      disk except for elastic collisions with the boundary and also a circular
      scatterer in the interior of the disk. We investigate the stability properties of
      some periodic orbits in annular billiards in which the scatterer is touching or
      close to the boundary. We analytically show that there exist linearly stable
      periodic orbits of an arbitrary period for scatterers with decreasing radii that
      are located near the boundary of the disk. As the position of the scatterer moves
      away from a symmetry line of a periodic orbit, the stability of periodic orbits
      changes from elliptic to hyperbolic, corresponding to a saddle-center
      bifurcation. When the scatterer is tangent to the boundary, the periodic orbit is
      parabolic. We prove that slightly changing the reflection angle of the orbit in
      the tangential situation leads to the existence of Kolmogorov-Arnold-Moser
      islands. Thus, we show that there exists a decreasing to zero sequence of open
      intervals of scatterer radii, along which the billiard table is not ergodic.

PMID- 28456179
TI  - Chimera-like states in structured heterogeneous networks.
AB  - Chimera-like states are manifested through the coexistence of synchronous and
      asynchronous dynamics and have been observed in various systems. To analyze the
      role of network topology in giving rise to chimera-like states, we study a
      heterogeneous network model comprising two groups of nodes, of high and low
      degrees of connectivity. The architecture facilitates the analysis of the system,
      which separates into a densely connected coherent group of nodes, perturbed by
      their sparsely connected drifting neighbors. It describes a synchronous behavior
      of the densely connected group and scaling properties of the induced
      perturbations.

PMID- 28456180
TI  - Stabilization of collapsing scroll waves in systems with random heterogeneities.
AB  - In three-dimensional reaction-diffusion systems, excitation waves may form and
      rotate around a one-dimensional phase singularity called the filament. If the
      filament forms a closed curve, it will shrink over time and eventually collapse.
      However, filaments may pin to non-reactive objects present in the medium,
      reducing their rate of collapse or even allowing them to persist indefinitely. We
      use numerical simulations to study how different arrangements of non-reactive
      spheres affect the dynamics of circular filaments. As the filament contracts, it
      gets closer to and eventually touches and pins to objects in its path. This
      causes two possible behaviors. The filament can detach from the spheres in its
      path, slowing down the rate of contraction, or it can remain pinned to a
      collection of spheres. In general, more or larger spheres increase the chance
      that the filament remains pinned, but there are exceptions. It is possible for a
      small number of small spheres to support the filament and possible for the
      filament to pass through a large number of large spheres. Our work yields
      insights into the pinning of scroll waves in excitable tissue such as cardiac
      muscle, where scar tissue acts in a way similar to the non-reactive domains.

PMID- 28456181
TI  - Comb-like Turing patterns embedded in Hopf oscillations: Spatially localized
      states outside the 2:1 frequency locked region.
AB  - A generic mechanism for the emergence of spatially localized states embedded in
      an oscillatory background is demonstrated by using a 2:1 frequency locking
      oscillatory system. The localization is of Turing type and appears in two space
      dimensions as a comb-like state in either pi phase shifted Hopf oscillations or
      inside a spiral core. Specifically, the localized states appear in absence of the
      well known flip-flop dynamics (associated with collapsed homoclinic snaking) that
      is known to arise in the vicinity of Hopf-Turing bifurcation in one space
      dimension. Derivation and analysis of three Hopf-Turing amplitude equations in
      two space dimensions reveal a local dynamics pinning mechanism for Hopf fronts,
      which in turn allows the emergence of perpendicular (to the Hopf front) Turing
      states. The results are shown to agree well with the comb-like core size that
      forms inside spiral waves. In the context of 2:1 resonance, these localized
      states form outside the 2:1 resonance region and thus extend the frequency
      locking domain for spatially extended media, such as periodically driven Belousov
      Zhabotinsky chemical reactions. Implications to chlorite-iodide-malonic-acid and
      shaken granular media are also addressed.

PMID- 28456182
TI  - Molecular dynamics simulation of nanobubble nucleation on rough surfaces.
AB  - Here, we study how nanobubbles nucleate on rough hydrophobic surfaces, using long
      time standard simulations to directly observe the kinetic pathways and using
      constrained simulations combined with the thermodynamic integration approach to
      quantitatively evaluate the corresponding free energy changes. Both methods
      demonstrate that a two-step nucleation route involving the formation of an
      intermediate state is thermodynamically favorable: at first, the system
      transforms from the Wenzel state (liquid being in full contact with the solid
      surface) to the Cassie state (liquid being in contact with the peaks of the rough
      surface) after gas cavities occur in the grooves (i.e., the Wenzel-to-Cassie
      transition); then, the gas cavities coalesce and form a stable surface nanobubble
      with pinned contact lines (i.e., the Cassie-to-nanobubble transition).
      Additionally, the free energy barriers for the two transitions show opposing
      dependencies on the degree of surface roughness, indicating that the surfaces
      with moderate roughness are favorable for forming stable surface nanobubbles.
      Moreover, the simulation results also reveal the coexistence and transition
      between the Wenzel, Cassie, and nanobubble states on rough surfaces.

PMID- 28456183
TI  - Energy-based truncation of multi-determinant wavefunctions in quantum Monte
      Carlo.
AB  - We present a method for truncating large multi-determinant expansions for use in
      diffusion Monte Carlo calculations. Current approaches use wavefunction-based
      criteria to perform the truncation. Our method is more intuitively based on the
      contribution each determinant makes to the total energy. We show that this
      approach gives consistent behaviour across systems with varying correlation
      character, which leads to effective error cancellation in energy differences.
      This is demonstrated through accurate calculations of the electron affinity of
      oxygen and the atomisation energy of the carbon dimer. The approach is simple and
      easy to implement, requiring only quantities already accessible in standard
      configuration interaction calculations.

PMID- 28456184
TI  - Vibronic properties of para-polyphenylene ethynylenes: TD-DFT insights.
AB  - The first singlet excited states of a series of para-polyphenylene ethynylenes
      (PPEs) are investigated using time-dependent density functional theory (TD-DFT).
      Vibronic absorption spectra are calculated and show excellent agreement with the
      experiments, thus validating the adequacy of TD-DFT for such systems. The
      vibronic structure is assigned to the excitation of a few typical stretching and
      bending modes. The significant discrepancy between the simulated vertical
      transition energies and the experimental absorption maxima in PPEs is underlined
      and explained. The evolution of the spectroscopic properties and of the
      electronic structure with the chain length is discussed and characterized.

PMID- 28456185
TI  - Dynamics of solid alanine by means of nuclear magnetic resonance relaxometry.
AB  - 1H nuclear magnetic resonance relaxometry was applied to investigate the dynamics
      of l-alanine in the solid phase (powder). The experimental studies were carried
      out in a very broad frequency range, covering four orders of magnitude-from 4 kHz
      to 40 MHz (referring to the 1H resonance frequency) in order to probe motional
      processes of much different time scales by a single experiment. To get access to
      the dynamics of different proton groups of alanine, the 1H spin-lattice
      relaxation measurements were performed for non-deuterated and partially
      deuterated alanine. The experiments were carried out in the temperature range of
      293 K-370 K (non-deuterated alanine) and 318 K-370 K (partially deuterated
      alanine). As a result of a thorough theoretical analysis of the extensive set of
      experimental results, three motional processes occurring on different time scales
      are identified and quantitatively described. The slowest process occurs on a time
      scale of MUs and it is attributed to the collective dynamics of a 3D hydrogen
      bond network of alanine, while the intermediate, attributed to the dynamics of
      the NH3 group, corresponds to the range of tenths of ns. The fast process
      describes the rotation of the CH3 group.

PMID- 28456186
TI  - Coulomb fission in multiply charged molecular clusters: Experiment and theory.
AB  - A series of three multiply charged molecular clusters, (C6H6)nz+ (benzene),
      (CH3CN)nz+ (acetonitrile), and (C4H8O)nz+ (tetrahydrofuran), where the charge z
      is either 3 or 4, have been studied for the purpose of identifying the patterns
      of behaviour close to the charge instability limit. Experiments show that on a
      time scale of ~10-4 s, ions close to the limit undergo Coulomb fission where the
      observed pathways exhibit considerable asymmetry in the sizes of the charged
      fragments and are all associated with kinetic (ejection) energies of between 1.4
      and 2.2 eV. Accurate kinetic energies have been determined through a computer
      simulation of peak profiles recorded in the experiments and the results modelled
      using a theory formulated to describe how charged particles of dielectric
      materials interact with one another [E. Bichoutskaia et al., J. Chem. Phys. 133,
      024105 (2010)]. The calculated electrostatic interaction energy between
      separating fragments gives an accurate account for the measured kinetic energies
      and also supports the conclusion that +4 ions fragment into +3 and +1 products as
      opposed to the alternative of two +2 fragments. This close match between the
      theory and experiment reinforces the assumption that a significant fraction of
      excess charge resides on the surfaces of the fragment ions. It is proposed that
      the high degree of asymmetry seen in the fragmentation patterns of the multiply
      charged clusters is due, in part, to limits imposed by the time window during
      which observations are made.

PMID- 28456187
TI  - Electronic structure of VxTi1-xSe2 in wide concentration region (0.06 <= x <=
      0.9).
AB  - An experimental study of the electronic structure of VxTi1-xSe2 system in a wide
      range of vanadium concentrations (x = 0.06-0.9) using x-ray photoelectron
      spectroscopy and resonant photoelectron spectroscopy has been performed. The
      partial charge transfer from the VSe2 to TiSe2 structural fragments is
      experimentally observed, and the most part of the charge is localized on the
      vanadium atoms in the VSe2 structural fragments.

PMID- 28456188
TI  - A new ab initio potential energy surface of LiClH (1A') system and quantum
      dynamics calculation for Li + HCl (v = 0, j = 0-2) -> LiCl + H reaction.
AB  - A new ab initio potential energy surface (PES) for the ground state of Li + HCl
      reactive system has been constructed by three-dimensional cubic spline
      interpolation of 36 654 ab initio points computed at the MRCI+Q/aug-cc-pV5Z level
      of theory. The title reaction is found to be exothermic by 5.63 kcal/mol (9
      kcal/mol with zero point energy corrections), which is very close to the
      experimental data. The barrier height, which is 2.99 kcal/mol (0.93 kcal/mol for
      the vibrationally adiabatic barrier height), and the depth of van der Waals
      minimum located near the entrance channel are also in excellent agreement with
      the experimental findings. This study also identified two more van der Waals
      minima. The integral cross sections, rate constants, and their dependence on
      initial rotational states are calculated using an exact quantum wave packet
      method on the new PES. They are also in excellent agreement with the experimental
      measurements.

PMID- 28456189
TI  - Metadynamic metainference: Convergence towards force field independent structural
      ensembles of a disordered peptide.
AB  - Metadynamic metainference has been recently introduced as a theoretical framework
      to determine structural ensembles by combining and weighting their noise multiple
      sources of experimental data with molecular mechanics force fields and
      metadynamics simulations. Here we build upon these initial developments to
      further extend and streamline the computational approach. We also show that
      metadynamic metainference can actually determine a structural ensemble for a
      disordered peptide that is essentially independent from the employed force field.
      We further show that it is possible to use a very computationally efficient
      implicit solvent force field in the place of very expensive state-of-the-art
      explicit solvent ones without a significant loss in accuracy.

PMID- 28456190
TI  - HCl dissociating on a rigid Au(111) surface: A six-dimensional quantum mechanical
      study on a new potential energy surface based on the RPBE functional.
AB  - The dissociative chemisorption of HCl on the Au(111) surface has recently been an
      interesting and important subject, regarding the discrepancy between the
      theoretical dissociation probabilities and the experimental sticking
      probabilities. We here constructed an accurate full-dimensional (six-dimensional
      (6D)) potential energy surface (PES) based on the density functional theory (DFT)
      with the revised Perdew-Burke-Ernzerhof (RPBE) functional, and performed 6D
      quantum mechanical (QM) calculations for HCl dissociating on a rigid Au(111)
      surface. The effects of vibrational excitations, rotational orientations, and
      site-averaging approximation on the present RPBE PES are investigated. Due to the
      much higher barrier height obtained on the RPBE PES than on the PW91 PES, the
      agreement between the present theoretical and experimental results is greatly
      improved. In particular, at the very low kinetic energy, the QM-RPBE dissociation
      probability agrees well with the experimental data. However, the computed QM-RPBE
      reaction probabilities are still markedly different from the experimental values
      at most of the energy regions. In addition, the QM-RPBE results achieve good
      agreement with the recent ab initio molecular dynamics calculations based on the
      RPBE functional at high kinetic energies.

PMID- 28456191
TI  - Atomistic simulations of wetting properties and water films on hydrophilic
      surfaces.
AB  - We use molecular simulations to investigate the wetting behavior of water at flat
      polar surfaces. Introducing a computational procedure based on thermodynamic
      integration methods, we determine the equilibrium water film thickness on the
      surface at given vapor density as well as the corresponding change of the surface
      free energy. The wetting film is relevant on polar surfaces near the wetting
      transition and significantly alters the surface contact angle. For thin films,
      the surface free energy change increases linearly with the thickness, as
      predicted by simple thermodynamic arguments. For thick films we observe
      deviations from linearity, which we rationalize by the formation of hydrogen
      bonds between water molecules in the film. Our approach provides an efficient and
      accurate technique to calculate the wetting properties of surface layers, which
      we verify by simulating water droplets on the surfaces.

PMID- 28456192
TI  - Perspective: C60+ and laboratory spectroscopy related to diffuse interstellar
      bands.
AB  - In the last 30 years, our research has focused on laboratory measurements of the
      electronic spectra of organic radicals and ions. Many of the species investigated
      were selected based on their potential astrophysical relevance, particularly in
      connection with the identification of appealing candidate molecules for the
      diffuse interstellar absorptions. Notably, carbon chains and derivatives
      containing hydrogen and nitrogen atoms in their neutral and ionic forms were
      studied. These data could be obtained after developing appropriate techniques to
      record spectra at low temperatures relevant to the interstellar medium. The
      measurement of gas phase laboratory spectra has enabled direct comparisons with
      astronomical data to be made and though many species were found to have
      electronic transitions in the visible where the majority of diffuse bands are
      observed, none of the absorptions matched the prominent interstellar features. In
      2015, however, the first carrier molecule was identified: C60+. This was achieved
      after the measurement of the electronic spectrum of C60+-He at 6K in a
      radiofrequency ion trap.

PMID- 28456193
TI  - Isotropic-nematic phase transition of uniaxial variable softness prolate and
      oblate ellipsoids.
AB  - Onsager's theory of the isotropic-nematic phase separation of rod shaped
      particles is generalized to include particle softness and attractions in the
      anisotropic interparticle force field. The procedure separates a scaled radial
      component from the angular integral part, the latter being treated in essentially
      the same way as in the original Onsager formulation. Building on previous
      treatments of more idealised hard-core particle models, this is a step toward
      representing more realistic rod-like systems and also allowing temperature (and
      in principle specific chemical factors) to be included at a coarse grained level
      in the theory. The focus of the study is on the coexisting concentrations and
      associated coexistence properties. Prolate and oblate ellipsoids are considered
      in both the small and very large aspect ratio limits. Approximations to the terms
      in the angular integrals derived assuming the very large (prolate) and very small
      (oblate) aspect ratios limits are compared with the formally exact treatment. The
      approximation for the second virial coefficient matches the exact solution for
      aspect ratios above about 20 for the prolate ellipsoids and less than ca. 0.05
      for the oblate ellipsoids from the numerical evaluation of the angular integrals.
      The temperature dependence of the coexistence density could be used to help
      determine the interaction potential of two molecules. The method works at
      temperatures above a certain threshold temperature where the second virial
      coefficient is positive.

PMID- 28456194
TI  - Thermodynamics of mixtures of patchy and spherical colloids of different sizes: A
      multi-body association theory with complete reference fluid information.
AB  - We present a theory to predict the structure and thermodynamics of mixtures of
      colloids of different diameters, building on our earlier work [A. Bansal et al.,
      J. Chem. Phys. 145, 074904 (2016)] that considered mixtures with all particles
      constrained to have the same size. The patchy, solvent particles have short-range
      directional interactions, while the solute particles have short-range isotropic
      interactions. The hard-sphere mixture without any association site forms the
      reference fluid. An important ingredient within the multi-body association theory
      is the description of clustering of the reference solvent around the reference
      solute. Here we account for the physical, multi-body clusters of the reference
      solvent around the reference solute in terms of occupancy statistics in a defined
      observation volume. These occupancy probabilities are obtained from enhanced
      sampling simulations, but we also present statistical mechanical models to
      estimate these probabilities with limited simulation data. Relative to an
      approach that describes only up to three-body correlations in the reference,
      incorporating the complete reference information better predicts the bonding
      state and thermodynamics of the physical solute for a wide range of system
      conditions. Importantly, analysis of the residual chemical potential of the
      infinitely dilute solute from molecular simulation and theory shows that whereas
      the chemical potential is somewhat insensitive to the description of the
      structure of the reference fluid, the energetic and entropic contributions are
      not, with the results from the complete reference approach being in better
      agreement with particle simulations.

PMID- 28456195
TI  - A simple model of solvent-induced symmetry-breaking charge transfer in excited
      quadrupolar molecules.
AB  - A simple model has been developed to describe the symmetry-breaking of the
      electronic distribution of AL-D-AR type molecules in the excited state, where D
      is an electron donor and AL and AR are identical acceptors. The origin of this
      process is usually associated with the interaction between the molecule and the
      solvent polarization that stabilizes an asymmetric and dipolar state, with a
      larger charge transfer on one side than on the other. An additional symmetry
      breaking mechanism involving the direct Coulomb interaction of the charges on the
      acceptors is proposed. At the same time, the electronic coupling between the two
      degenerate states, which correspond to the transferred charge being localised
      either on AL or AR, favours a quadrupolar excited state with equal amount of
      charge-transfer on both sides. Because of these counteracting effects, symmetry
      breaking is only feasible when the electronic coupling remains below a threshold
      value, which depends on the solvation energy and the Coulomb repulsion energy
      between the charges located on AL and AR. This model allows reproducing the
      solvent polarity dependence of the symmetry-breaking reported recently using time
      resolved infrared spectroscopy.

PMID- 28456196
TI  - First principles study of bimetallic Ni13-nAgn nano-clusters (n = 0-13):
      Structural, mixing, electronic, and magnetic properties.
AB  - Using spin polarized density functional theory based calculations, combined with
      ab initio molecular dynamics simulation, we carry out a systematic investigation
      of the bimetallic Ni13-nAgn nano-clusters, for all compositions. This includes
      prediction of the geometry, mixing behavior, and electronic properties. Our study
      reveals a tendency towards the formation of a core-shell like structure,
      following the rule of putting Ni in a high coordination site and Ag in a low
      coordination site. Our calculations predict negative mixing energies for the
      entire composition range, indicating mixing to be favored for the bimetallic
      small sized Ni-Ag clusters, irrespective of the compositions. The magic
      composition with the highest stability is found for the NiAg12 alloy cluster. We
      investigate the microscopic origin of a core-shell like structure with negative
      mixing energy, in which the Ni-Ag inter-facial interaction is found to play a
      role. We also study the magnetic properties of the Ni-Ag alloy clusters. The Ni
      dominated magnetism consists of parallel alignment of Ni moments while the tiny
      moments on Ag align in anti-parallel to Ni moments. The hybridization with the Ag
      environment causes reduction of Ni moment.

PMID- 28456197
TI  - Non-polymeric asymmetric binary glass-formers. II. Secondary relaxation studied
      by dielectric, 2H NMR, and 31P NMR spectroscopy.
AB  - We investigate the secondary (beta-) relaxations of an asymmetric binary glass
      former consisting of a spirobichroman derivative (SBC; Tg = 356 K) as the high-Tg
      component and the low-Tg component tripropyl phosphate (TPP; Tg = 134 K). The
      main relaxations are studied in Paper I [B. Potzschner et al., J. Chem. Phys.
      146, 164503 (2017)]. A high Tg contrast of DeltaTg = 222 K is put into effect in
      a non-polymeric system. Component-selective studies are carried out by combining
      results from dielectric spectroscopy (DS) for mass concentrations cTPP >= 60% and
      those from different methods of 2H and 31P NMR spectroscopy. In the case of NMR,
      the full concentration range (10% <= cTPP <= 100%) is covered. The neat
      components exhibit a beta-relaxation (beta1 (SBC) and beta2 (TPP)). The latter is
      rediscovered by DS in the mixtures for all concentrations with unchanged time
      constants. NMR spectroscopy identifies the beta-relaxations as being alike to
      those in neat glasses. A spatially highly restricted motion with angular
      displacement below +/-10 degrees  encompassing all molecules is involved. In the
      low temperature range, where TPP shows the typical 31P NMR echo spectra of the
      beta2-process, very similar spectral features are observed for the (deuterated)
      SBC component by 2H NMR, in addition to its "own" beta1-process observed at high
      temperatures. Apparently, the small TPP molecules enslave the large SBC molecules
      to perform a common hindered reorientation. The temperature dependence of the
      spin-lattice relaxation time of both components is the same and reveals an
      angular displacement of the SBC molecules somewhat smaller than that of TPP,
      though the time constants taubeta2 are the same. Furthermore, T1(T) of TPP in the
      temperature region of the beta2-process is absolutely the same as in the mixture
      TPP/polystyrene investigated previously. It appears that the manifestations of
      the beta-process introduced by one component are essentially independent of the
      second component. Finally, at cTPP <= 20% one finds indications that the beta2
      process starts to disintegrate. More and more TPP molecules get immobilized upon
      decreasing cTPP. We conclude that the beta-process is a cooperative process.

PMID- 28456198
TI  - Density functional investigation of the adsorption effects of PH3 and SH2 on the
      structure stability of the Au55 and Pt55 nanoclusters.
AB  - Although several studies have been reported for Pt55 and Au55 nanoclusters, our
      atomistic understanding of the interplay between the adsorbate-surface
      interactions and the mechanisms that lead to the formation of the distorted
      reduced core (DRC) structures, instead of the icosahedron (ICO) structure in gas
      phase, is still far from satisfactory. Here, we report a density functional
      theory (DFT) investigation of the role of the adsorption effects of PH3 (one lone
      pair of electrons) and SH2 (two lone pairs) on the relative stability of the Pt55
      and Au55 nanoclusters. In gas phase, we found that the DRC structures with 7 and
      9 atoms in the core region are about 5.34 eV (Pt55) and 2.20 eV (Au55) lower in
      energy than the ICO model with Ih symmetry and 13 atoms in the core region.
      However, the stability of the ICO structure increases by increasing the number of
      adsorbed molecules from 1 to 18, in which both DRC and ICO structures are nearly
      degenerate in energy at the limit of 18 ligands, which can be explained as
      follows. In gas phase, there is a strong compression of the cationic core region
      by the anionic surface atoms induced by the attractive Coulomb interactions
      (core+-surface-), and hence, the strain release is obtained by reducing the
      number of atoms in the cationic core region, which leads to the 55 atoms
      distorted reduced core structures. Thus, the Coulomb interactions between the
      core+ and surface- contribute to break the symmetry in the ICO55 structure. On
      the other hand, the addition of ligands on the anionic surface reduces the charge
      transfer between the core and surface, which contributes to decrease the Coulomb
      interactions and the strain on the core region of the ICO structure, and hence,
      it stabilizes a compact ICO structure. The same conclusion is obtained by adding
      van der Waals corrections to the plain DFT calculations. Similar results are
      obtained by the addition of steric effects, which are considered through the
      adsorption of triphenylphosphine (PPh3) molecules on Au55, in which the relative
      stability between ICO and DRC is the same as for PH3 and SH2. However, for Pt55,
      we found an inversion of stability due to the PPh3 ligand effects, where ICO has
      higher stability than DRC by 2.40 eV. Our insights are supported by several
      structural, electronic, and energetic analyses.

PMID- 28456199
TI  - Counterion accumulation effects on a suspension of DNA molecules: Equation of
      state and pressure-driven denaturation.
AB  - The study of the effects associated with the electrostatic properties of DNA is
      of fundamental importance to understand both its molecular properties at the
      single molecule level, like the rigidity of the chain, and its interaction with
      other charged bio-molecules, including other DNA molecules; such interactions are
      crucial to maintain the thermodynamic stability of the intra-cellular medium. In
      the present work, we combine the Poisson-Boltzmann mean-field theory with an
      irreversible thermodynamic approximation to analyze the effects of counterion
      accumulation inside DNA on both the denaturation profile of the chain and the
      equation of state of the suspension. To this end, we model the DNA molecule as a
      porous charged cylinder immersed in an aqueous solution. These thermo
      electrostatic effects are explicitly studied in the particular case of some genes
      for which damage in their sequence is associated with diffuse large B-cell
      lymphoma.

PMID- 28456200
TI  - Microscopic insight into thermodynamics of conformational changes of SAP-SLAM
      complex in signal transduction cascade.
AB  - The signalling lymphocytic activation molecule (SLAM) family of receptors,
      expressed by an array of immune cells, associate with SLAM-associated protein
      (SAP)-related molecules, composed of single SH2 domain architecture. SAP
      activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn
      complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3
      or SH2 interactions. This demands insight into this SAP mediated signalling
      cascade. Thermodynamics of the conformational changes are extracted from the
      histograms of dihedral angles obtained from the all-atom molecular dynamics
      simulations of this structurally well characterized SAP-SLAM complex. The results
      incorporate the binding induced thermodynamic changes of individual amino acid as
      well as the secondary structural elements of the protein and the solvent.
      Stabilization of the peptide partially comes through a strong hydrogen bonding
      network with the protein, while hydrophobic interactions also play a significant
      role where the peptide inserts itself into a hydrophobic cavity of the protein.
      SLAM binding widens SAP's second binding site for Fyn, which is the next step in
      the signal transduction cascade. The higher stabilization and less fluctuation of
      specific residues of SAP in the Fyn binding site, induced by SAP-SLAM
      complexation, emerge as the key structural elements to trigger the recognition of
      SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due
      to complexation not only throws deeper understanding in the established mode of
      SAP-SLAM interaction but also assists in the recognition of the relevant residues
      of the protein responsible for alterations in its activity.

PMID- 28456201
TI  - Light-responsive expansion-contraction of spherical nanoparticle grafted with
      azopolymers.
AB  - Due to the very importance for both fundamental research and technological
      applications, smart materials with stimuli-responsive properties have been
      studied intensively. Theoretical investigation contributes to this endeavor
      through constructing and analyzing a model system which captures main features of
      the corresponding complex material, wherefrom useful insight can be provided to
      the trial-and-error experiments. We here report a theoretical study on the smart
      spherical nanoparticle grafted with light-responsive azobenzene-containing
      polymers. Utilizing the photoisomerization ability of the azobenzene group,
      nanoparticles can undergo a light-induced expansion-contraction transition. The
      wormlike chain based single chain in mean field theory, which has been developed
      by us recently, is used to investigate this transition in detail. Exploring a
      large parameter space, our results definitely determine the parameters, including
      the chain length and effective Kuhn length of grafted chain, nanoparticle radius,
      grafting density, and position of the azobenzene group along the chain contour,
      to admit optimum light-responsive behavior of the smart nanoparticle, which
      provides a guide for experimentalists to design this type of material in a
      rational manner.

PMID- 28456202
TI  - Adsorption of methylene blue and its N-demethylated derivatives on the (111) face
      of coinage metals: The importance of dispersion interactions.
AB  - The adsorption of methylene blue and its N-demethylated derivatives on the (111)
      surface of three coinage metals is investigated using density functional theory
      with and without the inclusion of dispersion interactions. It is shown that the
      adsorption of these dye molecules on the metal surfaces can be largely classified
      as physisorption as the adsorption energy is dominated by dispersion
      interactions. While the molecules are found to adsorb on Au and Ag parallel to
      the surface with molecular geometries basically unaltered, the adsorption on
      Cu(111) features a butterfly configuration, accompanied by the largest adsorption
      energies among the three metal surfaces. The significant covalent character on
      Cu(111) is analyzed from the perspective of electronic structure.

PMID- 28456203
TI  - Coarse-graining strategy for molecular pair interactions: A reaction coordinate
      study for two- and three-dimensional systems.
AB  - We investigate and provide optimal sets of reaction coordinates for mixed pairs
      of molecules displaying polar, uniaxial, or spherical symmetry in two and three
      dimensions. These coordinates are non-redundant, i.e., they implicitly involve
      the molecules' symmetries. By tabulating pair interactions in these coordinates,
      resulting tables are thus minimal in length and require a minimal memory space.
      The intended fields of application are computer simulations of large ensembles of
      molecules or colloids with rather complex interactions in a fluid or liquid
      crystalline phase at low densities. Using effective interactions directly in the
      form of tables can help bridging the time and length scales without introducing
      errors stemming from any modeling procedure. Finally, we outline an exemplary
      computational methodology for gaining an effective pair potential in these
      coordinates, based on the Boltzmann inversion principle, by providing a step-by
      step recipe.

PMID- 28456204
TI  - Non-polymeric asymmetric binary glass-formers. I. Main relaxations studied by
      dielectric, 2H NMR, and 31P NMR spectroscopy.
AB  - In Paper I of this series of two papers we study the main relaxations of a binary
      glass former made of the low-Tg component tripropyl phosphate (TPP, Tg = 134 K)
      and of a specially synthesized (deuterated) spirobichroman derivative (SBC, Tg =
      356 K) as the non-polymeric high-Tg component for the full concentration range. A
      large Tg contrast of the neat components is put into effect. Dielectric
      spectroscopy and different techniques of 2H nuclear magnetic resonance (NMR) as
      well as of 31P NMR spectroscopy allow to selectively probe the dynamics of the
      components. For all concentrations, two well separated liquid-like processes are
      identified. The faster alpha2-process associated with the low-Tg component TPP
      shows pronounced dynamic heterogeneities reflected by quasi-logarithmic
      correlation functions at low TPP concentrations. The slower alpha1-process
      involves the reorientation of the high-Tg component SBC. Its correlation function
      is Kohlrausch-like as in neat glass formers. The corresponding time constants and
      consequently their glass transition temperatures Tg1 and Tg2 differ more the
      lower the TPP concentration is. Plasticizer and anti-plasticizer effect,
      respectively, is observed. At low temperatures a situation arises that the TPP
      molecules isotropically reorient in an arrested SBC matrix (Tg2 < T < Tg1). At T
      < Tg2 the liquid-like reorientation of TPP gets arrested too. We find indications
      that a fraction of the TPP molecule takes part in the slower alpha1-process of
      the high-Tg component. All the features known from polymer-plasticizer systems
      are rediscovered in this non-polymeric highly asymmetric binary mixture. In Paper
      II [B. Potzschner et al., J. Chem. Phys. 146, 164504 (2017)] we study the
      secondary (beta-) relaxations of the mixtures.

PMID- 28456206
TI  - Benchmark coupled-cluster g-tensor calculations with full inclusion of the two
      particle spin-orbit contributions.
AB  - We present a parallel implementation to compute electron spin resonance g-tensors
      at the coupled-cluster singles and doubles (CCSD) level which employs the ACES
      III domain-specific software tools for scalable parallel programming, i.e., the
      super instruction architecture language and processor (SIAL and SIP),
      respectively. A unique feature of the present implementation is the exact (not
      approximated) inclusion of the five one- and two-particle contributions to the g
      tensor [i.e., the mass correction, one- and two-particle paramagnetic spin-orbit,
      and one- and two-particle diamagnetic spin-orbit terms]. Like in a previous
      implementation with effective one-electron operators [J. Gauss et al., J. Phys.
      Chem. A 113, 11541-11549 (2009)], our implementation utilizes analytic CC second
      derivatives and, therefore, classifies as a true CC linear-response treatment.
      Therefore, our implementation can unambiguously appraise the accuracy of less
      costly effective one-particle schemes and provide a rationale for their
      widespread use. We have considered a large selection of radicals used previously
      for benchmarking purposes including those studied in earlier work and conclude
      that at the CCSD level, the effective one-particle scheme satisfactorily captures
      the two-particle effects less costly than the rigorous two-particle scheme. With
      respect to the performance of density functional theory (DFT), we note that
      results obtained with the B3LYP functional exhibit the best agreement with our
      CCSD results. However, in general, the CCSD results agree better with the
      experimental data than the best DFT/B3LYP results, although in most cases within
      the rather large experimental error bars.

PMID- 28456205
TI  - Water isotope effect on the thermostability of a polio viral RNA hairpin: A
      metadynamics study.
AB  - Oral polio vaccine is considered to be the most thermolabile of all the common
      childhood vaccines. Despite heavy water (D2O) having been known for a long time
      to stabilise attenuated viral RNA against thermodegradation, the molecular
      underpinnings of its mechanism of action are still lacking. Whereas,
      understanding the basis of D2O action is an important step that might reform the
      way other thermolabile drugs are stored and could possibly minimize the cold
      chain problem. Here using a combination of parallel tempering and well-tempered
      metadynamics simulation in light water (H2O) and in D2O, we have fully described
      the free energy surface associated with the folding/unfolding of a RNA hairpin
      containing a non-canonical basepair motif, which is conserved within the 3'
      untranslated region of poliovirus-like enteroviruses. Simulations reveal that in
      heavy water (D2O) there is a considerable increase of the stability of the folded
      basin as monitored through an intramolecular hydrogen bond (HB), size, shape, and
      flexibility of RNA structures. This translates into a higher melting temperature
      in D2O by 41 K when compared with light water (H2O). We have explored the
      hydration dynamics of the RNA, hydration shell around the RNA surface, and
      spatial dependence of RNA-solvent collective HB dynamics in the two water
      systems. Simulation in heavy water clearly showed that D2O strengthens the HB
      network in the solvent, lengthens inter-residue water-bridge lifetime, and
      weakens dynamical coupling of the hairpin to its solvation environment, which
      enhances the rigidity of solvent exposed sites of the native configurations. The
      results might suggest that like other added osmoprotectants, D2O can act as a
      thermostabilizer when used as a solvent.

PMID- 28456207
TI  - The importance of inner-shell electronic structure for enhancing the EUV
      absorption of photoresist materials.
AB  - In order to increase computation power and efficiency, the semiconductor industry
      continually strives to reduce the size of features written using lithographic
      techniques. The planned switch to a shorter wavelength extreme ultraviolet (EUV)
      source presents a challenge for the associated photoresists, which in their
      current manifestation show much poorer photoabsorption cross sections for the
      same dose. Here we consider the critical role that an inner-shell electronic
      structure might play in enhancing photoabsorption cross sections, which one can
      control by the choice of substituent elements in the photoresist. In order to
      increase the EUV sensitivity of current photoresists, it is critical to consider
      the inner-shell atomic structure of the elements that compose the materials. We
      validate this hypothesis using a series of halogenated organic molecules, which
      all have similar valence structures, but differ in the character of their semi
      core and deep valence levels. Using various implementations of time-dependent
      density functional theory, the absorption cross sections are computed for the
      model systems of CH3X, X = H, OH, F, Cl, Br, I, as well as a representative
      polymer fragment: 2-methyl-phenol and its halogenated analogues. Iodine has a
      particularly high cross section in the EUV range, which is due to delayed
      absorption by its 4d electrons. The computational results are compared to
      standard database values and experimental data when available. Generally we find
      that the states that dominate the EUV oscillator strength are generated by
      excitations of deep valence or semi-core electrons, which are primarily atomic
      like and relatively insensitive to the specific molecular structure.

PMID- 28456208
TI  - A new near-linear scaling, efficient and accurate, open-shell domain-based local
      pair natural orbital coupled cluster singles and doubles theory.
AB  - The Coupled-Cluster expansion, truncated after single and double excitations
      (CCSD), provides accurate and reliable molecular electronic wave functions and
      energies for many molecular systems around their equilibrium geometries. However,
      the high computational cost, which is well-known to scale as O(N6) with system
      size N, has limited its practical application to small systems consisting of not
      more than approximately 20-30 atoms. To overcome these limitations, low-order
      scaling approximations to CCSD have been intensively investigated over the past
      few years. In our previous work, we have shown that by combining the pair natural
      orbital (PNO) approach and the concept of orbital domains it is possible to
      achieve fully linear scaling CC implementations (DLPNO-CCSD and DLPNO-CCSD(T))
      that recover around 99.9% of the total correlation energy [C. Riplinger et al.,
      J. Chem. Phys. 144, 024109 (2016)]. The production level implementations of the
      DLPNO-CCSD and DLPNO-CCSD(T) methods were shown to be applicable to realistic
      systems composed of a few hundred atoms in a routine, black-box fashion on
      relatively modest hardware. In 2011, a reduced-scaling CCSD approach for high
      spin open-shell unrestricted Hartree-Fock reference wave functions was proposed
      (UHF-LPNO-CCSD) [A. Hansen et al., J. Chem. Phys. 135, 214102 (2011)]. After a
      few years of experience with this method, a few shortcomings of UHF-LPNO-CCSD
      were noticed that required a redesign of the method, which is the subject of this
      paper. To this end, we employ the high-spin open-shell variant of the N-electron
      valence perturbation theory formalism to define the initial guess wave function,
      and consequently also the open-shell PNOs. The new PNO ansatz properly converges
      to the closed-shell limit since all truncations and approximations have been made
      in strict analogy to the closed-shell case. Furthermore, given the fact that the
      formalism uses a single set of orbitals, only a single PNO integral
      transformation is necessary, which offers large computational savings. We show
      that, with the default PNO truncation parameters, approximately 99.9% of the
      total CCSD correlation energy is recovered for open-shell species, which is
      comparable to the performance of the method for closed-shells. UHF-DLPNO-CCSD
      shows a linear scaling behavior for closed-shell systems, while linear to
      quadratic scaling is obtained for open-shell systems. The largest systems we have
      considered contain more than 500 atoms and feature more than 10 000 basis
      functions with a triple-zeta quality basis set.

PMID- 28456209
TI  - Spin-polarized transport through a quantum ring with an embedded protein-like
      single-helical molecule.
AB  - We investigate the spin-polarized electron transport through a quantum ring whose
      arms are embedded by one protein-like single-helical molecule and one quantum
      dot, respectively. It is found that the inter-arm quantum interference leads to
      the enhancement of the spin polarization in this structure. Moreover, when local
      magnetic flux is applied through the ring, the spin polarization in the electron
      transport process, including the polarization strength and direction, can be
      further adjusted. Next in the finite-bias case, the spin polarization is also
      apparent and can be tuned by changing the magnetic flux or the dot level. This
      work provides a new scheme to manipulate the spin transport based on the single
      helical molecule.

PMID- 28456210
TI  - Rotation driven translational diffusion of polyatomic ions in water: A novel
      mechanism for breakdown of Stokes-Einstein relation.
AB  - While most of the existing theoretical and simulation studies have focused on
      simple, spherical, halide and alkali ions, many chemically, biologically, and
      industrially relevant electrolytes involve complex non-spherical polyatomic ions
      like nitrate, chlorate, and sulfate to name only a few. Interestingly, some
      polyatomic ions in spite of being larger in size show anomalously high
      diffusivity and therefore cause a breakdown of the venerable Stokes-Einstein (S
      E) relation between the size and diffusivity. Here we report a detailed analysis
      of the dynamics of anions in aqueous potassium nitrate (KNO3) and aqueous
      potassium acetate (CH3COOK) solutions. The two ions, nitrate (NO3-) and acetate
      (CH3CO2-), with their similar size show a large difference in diffusivity values.
      We present evidence that the translational motion of these polyatomic ions is
      coupled to the rotational motion of the ion. We show that unlike the acetate ion,
      nitrate ion with a symmetric charge distribution among all periphery oxygen atoms
      shows a faster rotational motion with large amplitude rotational jumps which
      enhances its translational motion due to translational-rotational coupling. By
      creating a family of modified-charge model systems, we have analysed the
      rotational motion of asymmetric polyatomic ions and the contribution of it to the
      translational motion. These model systems help clarifying and establishing the
      relative contribution of rotational motion in enhancing the diffusivity of the
      nitrate ion over the value predicted by the S-E relation and also over the other
      polyatomic ions having asymmetric charge distribution like the acetate ion. In
      the latter case, reduced rotational motion results in lower diffusivity values
      than those with symmetric charge distribution. We propose translational
      rotational coupling as a general mechanism of the breakdown of the S-E relation
      in the case of polyatomic ions.

PMID- 28456211
TI  - Controlling charge transport mechanisms in molecular junctions: Distilling
      thermally induced hopping from coherent-resonant conduction.
AB  - The electrical conductance of molecular junctions may depend strongly on the
      temperature and weakly on molecular length, under two distinct mechanisms: phase
      coherent resonant conduction, with charges proceeding via delocalized molecular
      orbitals, and incoherent thermally assisted multi-step hopping. While in the case
      of coherent conduction, the temperature dependence arises from the broadening of
      the Fermi distribution in the metal electrodes, in the latter case it corresponds
      to electron-vibration interaction effects on the junction. With the objective to
      distill the thermally activated hopping component, thus exposing intrinsic
      electron-vibration interaction phenomena on the junction, we suggest the design
      of molecular junctions with "spacers," extended anchoring groups that act to
      filter out phase-coherent resonant electrons. Specifically, we study the
      electrical conductance of fixed-gap and variable-gap junctions that include a
      tunneling block, with spacers at the boundaries. Using numerical simulations and
      analytical considerations, we demonstrate that in our design, resonant conduction
      is suppressed. As a result, the electrical conductance is dominated by two
      (rather than three) mechanisms: superexchange (deep tunneling) and multi-step
      thermally induced hopping. We further exemplify our analysis on DNA junctions
      with an A:T block serving as a tunneling barrier. Here, we show that the
      electrical conductance is insensitive to the number of G:C base-pairs at the
      boundaries. This indicates that the tunneling-to-hopping crossover revealed in
      such sequences truly corresponds to the properties of the A:T barrier.

PMID- 28456212
TI  - Decisive test of the ideal behavior of tetra-PEG gels.
AB  - The objective of this work is to investigate the thermodynamic and scattering
      behavior of tetra-poly(ethylene glycol) (PEG) gels. Complementary measurements,
      including osmotic swelling pressure, elastic modulus, and small angle neutron
      scattering (SANS), are reported for a series of tetra-PEG gels made from
      different molecular weight precursor chains at different concentrations. Analysis
      of the osmotic swelling pressure vs polymer volume fraction curves makes it
      possible to separate the elastic and mixing contributions of the network free
      energy. It is shown that in tetra-PEG gels these free energy components are
      additive. The elastic term varies with the one-third power of the polymer volume
      fraction and its numerical value is equal to the shear modulus obtained from
      independent mechanical measurements. The mixing pressure of the cross-linked
      polymer is slightly smaller than that of the corresponding solution of the
      uncross-linked polymer of infinite molecular weight but it exhibits similar
      dependence on the polymer concentration. The observed deviation between the
      osmotic mixing pressures of the gel and the solution can be attributed to the
      presence of small amount of structural inhomogeneities frozen-in by the cross
      links. SANS reveals that the scattering response of tetra-PEG gel is mainly
      governed by the thermodynamic concentration fluctuations of the network, i.e.,
      the contribution from static inhomogeneities to the SANS signal is small.

PMID- 28456213
TI  - Assessment of range-separated functionals in the presence of implicit solvent:
      Computation of oxidation energy, reduction energy, and orbital energy.
AB  - Recently, we have investigated the ionization potential (IP) theorem for some
      small molecules in the presence of external electric field [M. P. Borpuzari et
      al., J. Chem. Phys. 144, 164113 (2016)]. In this article, we assess the
      performance of some density functionals, local density approximation, generalized
      gradient approximation (GGA), hybrid, meta-GGA hybrid, and range-separated
      functionals in the presence of two different solvent dielectrics, water and
      cyclohexane, in reproducing the vertical oxidation energy, reduction energy, and
      the frontier orbital energies. We also study the accessibility of different
      computational solvent models like the polarizable continuum model (PCM) and non
      equilibrium PCM (NEPCM) in reproducing the desired properties. In general, the
      range-separated functionals do not perform well in reproducing orbital energies
      in the PCM. Range separation with the NEPCM is better. It is found that CAM
      B3LYP, M06-2X, and omegaB97XD functionals reproduce highest occupied molecular
      orbital energy in solvents, which may be due to the cancellation of PCM and
      density functional theory errors. Finally, we have tested the validity of the IP
      theorem in the solvent environment.

PMID- 28456214
TI  - Communication: Appearance of undershoots in start-up shear: Experimental findings
      captured by tumbling-snake dynamics.
AB  - Our experimental data unambiguously show (i) a damping behavior (the appearance
      of an undershoot following the overshoot) in the transient shear viscosity of a
      concentrated polymeric solution, and (ii) the absence of a corresponding behavior
      in the transient normal stress coefficients. Both trends are shown to be
      quantitatively captured by the bead-link chain kinetic theory for concentrated
      polymer solutions and entangled polymer melts proposed by Curtiss and Bird,
      supplemented by a non-constant link tension coefficient that we relate to the
      nematic order parameter. The observed phenomena are attributed to the tumbling
      behavior of the links, triggered by rotational fluctuations, on top of reptation.
      Using model parameters deduced from stationary data, we calculate the transient
      behavior of the stress tensor for this "tumbling-snake" model after startup of
      shear flow efficiently via simple Brownian dynamics. The unaltered method is
      capable of handling arbitrary homogeneous flows and has the promising capacity to
      improve our understanding of the transient behavior of concentrated polymer
      solutions.

PMID- 28456215
TI  - Field-theoretic simulations of block copolymer nanocomposites in a constant
      interfacial tension ensemble.
AB  - Block copolymers, due to their ability to self-assemble into periodic structures
      with long range order, are appealing candidates to control the ordering of
      functionalized nanoparticles where it is well-accepted that the spatial
      distribution of nanoparticles in a polymer matrix dictates the resulting material
      properties. The large parameter space associated with block copolymer
      nanocomposites makes theory and simulation tools appealing to guide experiments
      and effectively isolate parameters of interest. We demonstrate a method for
      performing field-theoretic simulations in a constant volume-constant interfacial
      tension ensemble (nVgammaT) that enables the determination of the equilibrium
      properties of block copolymer nanocomposites, including when the composites are
      placed under tensile or compressive loads. Our approach is compatible with the
      complex Langevin simulation framework, which allows us to go beyond the mean
      field approximation. We validate our approach by comparing our nVgammaT approach
      with free energy calculations to determine the ideal domain spacing and modulus
      of a symmetric block copolymer melt. We analyze the effect of numerical and
      thermodynamic parameters on the efficiency of the nVgammaT ensemble and
      subsequently use our method to investigate the ideal domain spacing, modulus, and
      nanoparticle distribution of a lamellar forming block copolymer nanocomposite. We
      find that the nanoparticle distribution is directly linked to the resultant
      domain spacing and is dependent on polymer chain density, nanoparticle size, and
      nanoparticle chemistry. Furthermore, placing the system under tension or
      compression can qualitatively alter the nanoparticle distribution within the
      block copolymer.

PMID- 28456216
TI  - Nonequilibrium generalised Langevin equation for the calculation of heat
      transport properties in model 1D atomic chains coupled to two 3D thermal baths.
AB  - We use a generalised Langevin equation scheme to study the thermal transport of
      low dimensional systems. In this approach, the central classical region is
      connected to two realistic thermal baths kept at two different temperatures [H.
      Ness et al., Phys. Rev. B 93, 174303 (2016)]. We consider model Al systems, i.e.,
      one-dimensional atomic chains connected to three-dimensional baths. The thermal
      transport properties are studied as a function of the chain length N and the
      temperature difference DeltaT between the baths. We calculate the transport
      properties both in the linear response regime and in the non-linear regime. Two
      different laws are obtained for the linear conductance versus the length of the
      chains. For large temperatures (T?500 K) and temperature differences (DeltaT?500
      K), the chains, with N>18 atoms, present a diffusive transport regime with the
      presence of a temperature gradient across the system. For lower temperatures
      (T?500 K) and temperature differences (DeltaT?400 K), a regime similar to the
      ballistic regime is observed. Such a ballistic-like regime is also obtained for
      shorter chains (N<=15). Our detailed analysis suggests that the behaviour at
      higher temperatures and temperature differences is mainly due to anharmonic
      effects within the long chains.

PMID- 28456217
TI  - A new method for calibrating hygrometers.
AB  - In this study, a new method was proposed for calibrating hygrometers. The
      moisture permeation cylinder, which was used to measure the water vapor
      permeability of fabrics, was used to generate various levels of relative
      humidity. A dry nitrogen stream was employed to sweep the water vapor away. It
      was deduced that the relative humidity of the outgoing nitrogen stream was
      negatively correlated to the volumetric flow rate of nitrogen stream, i.e., the
      lower the volumetric flow rate, the higher the relative humidity. The hygrometer
      HMT 333 was chosen to measure the relative humidity of the outgoing nitrogen
      stream at five levels. The test data indicated that good agreement was observed
      between the measured humidity and the observed humidity from the Vaisala, Inc.
      Moreover, this method offers high sensitivity and fast response. Therefore, the
      relative humidity of the outgoing nitrogen stream can be used as a secondary
      humidity reference.

PMID- 28456218
TI  - Note: Experimental setup for measuring the barocaloric effect in polymers:
      Application to natural rubber.
AB  - Barocaloric materials have shown to be promising alternatives to the conventional
      vapor-compression refrigeration technologies. Nevertheless, barocaloric effect
      (sigmab-CE) has not been extensively examined for many classes of materials up to
      now. Aiming at fulfilling this gap, the present paper describes the development
      of a high-pressure experimental setup for measuring the sigmab-CE in polymers.
      The design allows simultaneous measurements of temperature, pressure, and strain
      during the barocaloric cycle. The system proved to be fully functional through
      basic experiments using natural rubber. Samples exhibited large temperature
      variations associated with the sigmab-CE. Strain-temperature curves were also
      obtained, which could allow indirect measurements of the isothermal entropy
      change.

PMID- 28456219
TI  - Lactate threshold by muscle electrical impedance in professional rowers.
AB  - Lactate threshold (LT) is one of the physiological parameters usually used in
      rowing sport training prescription because it indicates the transitions from
      aerobic to anaerobic metabolism. Assessment of LT is classically based on a
      series of values of blood lactate concentrations obtained during progressive
      exercise tests and thus has an invasive aspect. The feasibility of noninvasive LT
      estimative through bioelectrical impedance spectroscopy (BIS) data collected in
      thigh muscles during rowing ergometer exercise tests was investigated. Nineteen
      professional rowers, age 19 (mean) +/- 4.8 (standard deviation) yr, height 187.3
      +/- 6.6 cm, body mass 83 +/- 7.7 kg, and training experience of 7 +/- 4 yr, were
      evaluated in a rowing ergometer progressive test with paired measures of blood
      lactate concentration and BIS in thigh muscles. Bioelectrical impedance data were
      obtained by using a bipolar method of spectroscopy based on the current response
      to a voltage step. An electrical model was used to interpret BIS data and to
      derive parameters that were investigated to estimate LT noninvasively. From the
      serial blood lactate measurements, LT was also determined through Dmax method
      (LTDmax). The zero crossing of the second derivative of kinetic of the
      capacitance electrode (Ce), one of the BIS parameters, was used to estimate LT.
      The agreement between the LT estimates through BIS (LTBIS) and through Dmax
      method (LTDmax) was evaluated using Bland-Altman plots, leading to a mean
      difference between the estimates of just 0.07 W and a Pearson correlation
      coefficient r = 0.85. This result supports the utilization of the proposed method
      based on BIS parameters for estimating noninvasively the lactate threshold in
      rowing.

PMID- 28456220
TI  - A double vacuum window mechanism for space-borne applications.
AB  - We present a vacuum window mechanism that is useful for applications requiring
      two different vacuum windows in series, with one of them movable and resealable.
      Such applications include space borne instruments that can benefit from a thin
      vacuum window at low ambient pressures but must also have an optically open
      aperture at atmospheric pressures. We describe the implementation and successful
      operation with the E and B experiment balloon-borne payload, a millimeter-wave
      instrument designed to measure the polarization of the cosmic microwave
      background radiation.

PMID- 28456221
TI  - A novel multi-jet burner for hot flue gases of wide range of temperatures and
      compositions for optical diagnostics of solid fuels gasification/combustion.
AB  - A novel multi-jet burner was built to provide one-dimensional laminar flat flames
      with a wide range of variable parameters for multipurpose quantitative optical
      measurements. The burner is characterized by two independent plenum chambers, one
      supporting a matrix of 181 laminar jet flames and the other supporting a co-flow
      from a perforated plate with small holes evenly distributed among the jets. A
      uniform rectangular burned gas region of 70 mm * 40 mm can be generated, with a
      wide range of temperatures and equivalence ratios by controlling independently
      the gas supplies to the two plenum chambers. The temperature of the hot gas can
      be adjusted from 1000 K to 2000 K with different flame conditions. The burner is
      designed to seed additives in gas or liquid phase to study homogeneous reactions.
      The large uniform region can be used to burn solid fuels and study heterogeneous
      reactions. The temperature was measured using two-line atomic fluorescence
      thermometry and the temperature profile at a given height above the burner was
      found to be flat. Different types of optical diagnostic techniques, such as line
      of sight absorption or laser-induced fluorescence, can be easily applied in the
      burner, and as examples, two typical measurements concerning biomass combustion
      are demonstrated.

PMID- 28456222
TI  - Coarse spectral characterization of warm x-rays at the Z facility using a
      filtered thermoluminescent dosimeter array.
AB  - A new collimated filtered thermoluminescent dosimeter (TLD) array has been
      developed at the Z facility to characterize warm x-rays (hnu > 10 keV) produced
      by Z pinch radiation sources. This array includes a Kapton debris shield assembly
      to protect the TLDs from the source debris, a collimator array to limit the field
      of view of the TLDs to the source region, a filter wheel containing filters of
      aluminum, copper and tungsten up to 3 mm thick to independently filter each TLD,
      and a hermetically sealed cassette containing the TLDs as well as tungsten
      shielding on the sides and back of the array to minimize scattered radiation
      reaching the TLDs. Experimental results from a krypton gas puff and silver wire
      array shot are analyzed using two different functional forms of the energy
      spectrum to demonstrate the ability of this diagnostic to consistently extend the
      upper end of the x-ray spectrum characterization from ~50 keV to >1 MeV.

PMID- 28456223
TI  - Polarizers, optical bridges, and Sagnac interferometers for nanoradian
      polarization rotation measurements.
AB  - The ability to measure nanoradian polarization rotations, thetaF, in the photon
      shot noise limit is investigated for partially crossed polarizers (PCP), a static
      Sagnac interferometer, and an optical bridge, each of which can in principle be
      used in this limit with near equivalent figures-of-merit (FOM). In practice a
      bridge to PCP/Sagnac source noise rejection ratio of 1/4thetaF2 enables the
      bridge to operate in the photon shot noise limit even at high light intensities.
      The superior performance of the bridge is illustrated via the measurement of a 3
      nrad rotation arising from an axial magnetic field of 0.9 nT applied to a terbium
      gallium garnet. While the Sagnac is functionally equivalent to the PCP in terms
      of the FOM, unlike the PCP it is able to discriminate between rotations with
      different time (T) and parity (P) symmetries. The Sagnac geometry implemented
      here is similar to that used elsewhere to detect non-reciprocal (T-P) rotations
      like those due to the Faraday effect. Using a Jones' matrix approach, novel
      Sagnac geometries uniquely sensitive to non-reciprocal TP- (e.g. magneto-electric
      or magneto-chiral) rotations, as well as to reciprocal rotations (e.g. due to
      linear birefringence, TP, or to chirality, TP-) are proposed.

PMID- 28456224
TI  - A fast edge charge exchange recombination spectroscopy system at the ASDEX
      Upgrade tokamak.
AB  - In this work, a new type of high through-put Czerny-Turner spectrometer has been
      developed which allows us to acquire multiple channels simultaneously with a
      repetition time on the order of 10 MUs at different wavelengths. The spectrometer
      has been coupled to the edge charge exchange recombination system at ASDEX
      Upgrade which has been recently refurbished with new lines of sight. Construction
      features, calibration methods, and initial measurements obtained with the new
      setup will be presented.

PMID- 28456225
TI  - Note: Production of stable colloidal probes for high-temperature atomic force
      microscopy applications.
AB  - For the application of colloidal probe atomic force microscopy at high
      temperatures (>500 K), stable colloidal probe cantilevers are essential. In this
      study, two new methods for gluing alumina particles onto temperature stable
      cantilevers are presented and compared with an existing method for borosilicate
      particles at elevated temperatures as well as with cp-cantilevers prepared with
      epoxy resin at room temperature. The durability of the fixing of the particle is
      quantified with a test method applying high shear forces. The force is calculated
      with a mechanical model considering both the bending as well as the torsion on
      the colloidal probe.

PMID- 28456226
TI  - Experimental investigation on electrical characteristics and dose measurement of
      dielectric barrier discharge plasma device used for therapeutic application.
AB  - In this research, a Dielectric Barrier Discharge (DBD) plasma device operating in
      air has been made. The electrical characteristics of this device like
      instantaneous power, dissipated power, and discharge capacitance have been
      measured. Also, the effects of applied voltage on the dissipated power and
      discharge capacitance of the device have been investigated. The determination of
      electrical parameters is important in DBD plasma device used in living tissue
      treatment for choosing the proper treatment doses and preventing the destructive
      effects. The non-thermal atmospheric pressure DBD plasma source was applied for
      studying the acceleration of blood coagulation time, in vitro and wound healing
      time, in vivo. The citrated blood drops coagulated within 5 s treatment time by
      DBD plasma. The effects of plasma temperature and electric field on blood
      coagulation have been studied as an affirmation of the applicability of the
      constructed device. Also, the effect of constructed DBD plasma on wound healing
      acceleration has been investigated.

PMID- 28456227
TI  - Development of a bio-magnetic measurement system and sensor configuration
      analysis for rats.
AB  - Magnetoencephalography (MEG) based on superconducting quantum interference
      devices enables the measurement of very weak magnetic fields (10-1000 fT)
      generated from the human or animal brain. In this article, we introduce a small
      MEG system that we developed specifically for use with rats. Our system has the
      following characteristics: (1) variable distance between the pick-up coil and
      outer Dewar bottom (~5 mm), (2) small pick-up coil (4 mm) for high spatial
      resolution, (3) good field sensitivity (45~ 80fT/cm/Hz), (4) the sensor interval
      satisfies the Nyquist spatial sampling theorem, and (5) small source localization
      error for the region to be investigated. To reduce source localization error, it
      is necessary to establish an optimal sensor layout. To this end, we simulated
      confidence volumes at each point on a grid on the surface of a virtual rat head.
      In this simulation, we used locally fitted spheres as model rat heads. This
      enabled us to consider more realistic volume currents. We constrained the model
      such that the dipoles could have only four possible orientations: the x- and y
      axes from the original coordinates, and two tangentially layered dipoles (local x
      and y-axes) in the locally fitted spheres. We considered the confidence volumes
      according to the sensor layout and dipole orientation and positions. We then
      conducted a preliminary test with a 4-channel MEG system prior to manufacturing
      the multi-channel system. Using the 4-channel MEG system, we measured rat
      magnetocardiograms. We obtained well defined P-, QRS-, and T-waves in rats with a
      maximum value of 15 pT/cm. Finally, we measured auditory evoked fields and steady
      state auditory evoked fields with maximum values 400 fT/cm and 250 fT/cm,
      respectively.

PMID- 28456228
TI  - A high-precision digital integrator based on the Romberg algorithm.
AB  - An integrator is widely used for measurement in the field of power systems, and
      it is a key technology in signal processing. According to research on the digital
      integrator based on the traditional Newton-Cotes algorithm, the high-frequency
      response of the low-order Cotes formula is usually poor and the design of the
      transfer function introduced by the high-order Cotes formula is too complex. In
      this paper, we analyze the error between the composite Newton-Cotes algorithm and
      the ideal transfer function. One signal was sampled using the normal sampling
      frequency and the other signal was sampled using half the normal sampling
      frequency. The two signals were weighted based on the Romberg algorithm. Thus,
      the precision of the digital integrator was improved, and the design difficulty
      was reduced for algorithms of the same order. The simulation and test results
      show that the proposed digital integrator has better transient and steady
      performance, and also has a lower error, which is less than 0.01%.

PMID- 28456229
TI  - Note: Development of a new Bridgman-type high pressure cell for accurate
      dielectric measurements.
AB  - We developed a new high pressure cell which allows us to perform accurate
      dielectric measurements above 3 GPa. The developed cell is based on Bridgman type
      opposed anvil cells with electrodes immersed into holes in the anvils in order to
      make the electrode area constant under compression. As a feasibility experiment,
      dielectric measurements for H2O were conducted up to 6.6 GPa and obtained
      dielectric constants are well consistent with previous studies.

PMID- 28456230
TI  - New density profile reconstruction methods in X-mode reflectometry.
AB  - The reconstruction method published by Bottollier-Curtet and Ichtchenko in 1987
      has been the standard method of density profile reconstruction for X-mode
      reflectometry ever since, with only minor revision. Envisaging improved accuracy
      and stability of the reconstruction method, functions more complex than the
      linear are evaluated here to describe the refractive index shape in each
      integration step. The stability and accuracy obtained when using parabolic and
      fixed or adaptative fractional power functions are compared to the previous
      method and tested against spurious events and phase noise. The developed relation
      from the plasma parameters to the best integration shapes allows for the
      optimization of the reconstruction for any profile shape. In addition, the
      density profiles can be reconstructed using less probing frequencies without
      accuracy loss, which speed up the reconstruction algorithm and enable real-time
      monitoring of faster density profile evolution.

PMID- 28456231
TI  - A memory efficient implementation scheme of Gauss error function in a Laguerre
      Volterra network for neuroprosthetic devices.
AB  - Cognitive neural prosthesis is a manmade device which can be used to restore or
      compensate for lost human cognitive modalities. The generalized Laguerre-Volterra
      (GLV) network serves as a robust mathematical underpinning for the development of
      such prosthetic instrument. In this paper, a hardware implementation scheme of
      Gauss error function for the GLV network targeting reconfigurable platforms is
      reported. Numerical approximations are formulated which transform the computation
      of nonelementary function into combinational operations of elementary functions,
      and memory-intensive look-up table (LUT) based approaches can therefore be
      circumvented. The computational precision can be made adjustable with the
      utilization of an error compensation scheme, which is proposed based on the
      experimental observation of the mathematical characteristics of the error
      trajectory. The precision can be further customizable by exploiting the run-time
      characteristics of the reconfigurable system. Compared to the polynomial
      expansion based implementation scheme, the utilization of slice LUTs, occupied
      slices, and DSP48E1s on a Xilinx XC6VLX240T field-programmable gate array has
      decreased by 94.2%, 94.1%, and 90.0%, respectively. While compared to the look-up
      table based scheme, 1.0*1017 bits of storage can be spared under the maximum
      allowable error of 1.0*10-3. The proposed implementation scheme can be employed
      in the study of large-scale neural ensemble activity and in the design and
      development of neural prosthetic device.

PMID- 28456233
TI  - Absolute optical responsivity down to the photon counting level with a
      photomultiplier tube.
AB  - A novel method is presented for evaluation of the absolute optical responsivity
      of a photomultiplier tube (PMT) at optical powers down to the photon counting
      level under visible light. This method is based on a combination of the
      calibrated responsivity and nonlinearity corrections using a silicon photodiode
      and a PMT. The evaluation results with the PMT enable accurate determination of
      the absolute optical responsivity over a wide power range of 10-11 W to 10-16 W
      under visible light. This method provides validation of both the photon counting
      efficiency of a PMT and of accurate optical measurement with attenuators at the
      photon counting level.

PMID- 28456232
TI  - New method of extracting information of arterial oxygen saturation based on
      ?|??|.
AB  - Noninvasive detection of oxygen saturation with near-infrared spectroscopy has
      been widely used in clinics. In order to further enhance its detection precision
      and reliability, this paper proposes a method of time domain absolute difference
      summation (?|Delta|) based on a dynamic spectrum. In this method, the ratio of
      absolute differences between intervals of two differential sampling points at the
      same moment on logarithm photoplethysmography signals of red and infrared light
      was obtained in turn, and then they obtained a ratio sequence which was screened
      with a statistical method. Finally, use the summation of the screened ratio
      sequence as the oxygen saturation coefficient Q. We collected 120 reference
      samples of SpO2 and then compared the result of two methods, which are ?|Delta|
      and peak-peak. Average root-mean-square errors of the two methods were 3.02% and
      6.80%, respectively, in the 20 cases which were selected randomly. In addition,
      the average variance of Q of the 10 samples, which were obtained by the new
      method, reduced to 22.77% of that obtained by the peak-peak method. Comparing
      with the commercial product, the new method makes the results more accurate.
      Theoretical and experimental analysis indicates that the application of the
      ?|Delta| method could enhance the precision and reliability of oxygen saturation
      detection in real time.

PMID- 28456234
TI  - Development of 2-D horn-antenna millimeter-wave imaging device (HMID) for the
      plasma diagnostics.
AB  - The two-dimensional (2-D) Horn-antenna Millimeter-wave Imaging Device (HMID) has
      been developed for the O-mode Microwave Imaging Reflectometry (O-MIR) in the
      Large Helical Device (LHD). The detectable frequency range of the HMID is 23-33
      GHz, which corresponds to the cutoff electron density of 0.8-1.5 * 1019 m-3 in
      the O-MIR. The HMID is a 2-D imaging device that improves on the horn-antenna
      mixer array, which had been developed for the X-mode MIR in the LHD. In the HMID,
      the signal (RF) wave from the horn antenna is transmitted to the microstrip line
      by the finline transmitter, and this is mixed by the double-balanced-mixer with
      the local oscillation wave that is fed by a coaxial cable. By using the HMID, the
      MIR optical system can be significantly simplified.

PMID- 28456235
TI  - Enhanced accuracy of x-ray spectra reconstruction from filtered diode array
      measurements by adding a time integrated spectrometer.
AB  - A new approach for the spectral reconstruction of time-dependent emission of soft
      x-ray sources based on the measurement of filtered x-ray diode array systems is
      suggested. Two reconstruction methods, based on this approach, are demonstrated
      using both simulated and measured data. The methods use the filtered x-ray diode
      measurement together with a co-aligned, time-integrated, spectrally resolved
      measurement, such as transmission grating spectroscopy. The additional
      experimental information allows for high accuracy spectral reconstruction, even
      for plasmas far from local thermodynamic equilibrium where the traditional
      reconstruction methods may miss some important source spectral features. For the
      demonstrated cases, the accuracy of the new reconstruction methods is better than
      10% for the energy dependent flux and 1% of the total flux, which is higher than
      the accuracy of previous methods and better than the accuracy of the measurement
      itself.

PMID- 28456236
TI  - Calibration and characterization of a highly efficient spectrometer in von Hamos
      geometry for 7-10 keV x-rays.
AB  - We have built an absolutely calibrated, highly efficient, Bragg crystal
      spectrometer in von Hamos geometry. This zinc von Hamos spectrometer uses a
      crystal made from highly oriented pyrolytic graphite that is cylindrically bent
      along the non-dispersive axis. It is tuned to measure x-ray spectra in the 7-10
      keV range and has been designed to be used on a Ten Inch Manipulator for the
      Omega and OmegaEP target chambers at the Laboratory for Laser Energetics in
      Rochester, USA. Significant shielding strategies and fluorescence mitigation have
      been implemented in addition to an imaging plate detector making it well suited
      for experiments in high-intensity environments. Here we present the design and
      absolute calibration as well as mosaicity and integrated reflectivity
      measurements.

PMID- 28456237
TI  - Note: An improved low-frequency correction technique for piezoelectric force
      sensors in high-speed nanopositioning systems.
AB  - Piezoelectric force and position sensors provide high sensitivity but are limited
      at low frequencies due to their high-pass response which complicates the direct
      application of integral control. To overcome this issue, an additional sensor or
      low-frequency correction method is typically employed. However, these approaches
      introduce an additional first-order response that must be higher than the high
      pass response of the piezo and interface electronics. This article describes a
      simplified method for low-frequency correction that uses the piezoelectric sensor
      as an electrical component in a filter circuit. The resulting response is first
      order, rather than second-order, with a cut-off frequency equal to that of a
      buffer circuit with the same input resistance. The proposed method is
      demonstrated to allow simultaneous damping and tracking control of a high-speed
      vertical nanopositioning stage.

PMID- 28456238
TI  - A direct differential method for measuring thermal conductivity of thin films.
AB  - Over the past two decades, significant progress in the thermal metrology for thin
      films and wires has enabled new understanding of the thermal conductivity of
      nanostructures. However, a large variation in the measured thermal conductivity
      of similar nanostructured samples has been observed. In addition to potential
      differences from sample-to-sample, measurement uncertainty contributes to the
      observed variation in measured properties. Many now standard micro/nanoscale
      thermal measurement techniques require extensive calibration of the properties of
      the substrate and support structures and this calibration contributes to
      uncertainty. Within this work, we develop a simple, direct differential
      electrothermal measurement of thermal conductivity of micro/nanoscale sample
      films by extending conventional steady state electrothermal approaches.
      Specifically, we leverage a cross-beam measurement structure consisting of a
      suspended, composite heater beam (metal on silicon) with the sample structure
      (silicon) extending at a right angle from the center of the heater beam, in a
      configuration similar to the T-type measurements used for fibers and nanotubes.
      To accurately resolve the thermal conductivity of the sample, the steady-state
      Joule heating response of the cross-beam structure is measured. Then, the sample
      is detached from the heater beam with a Focused Ion Beam (FIB) tool enabling
      direct characterization of the composite heater beam thermal properties. The
      differential measurement of the structure before and after FIB cut enables direct
      extraction of the sample thermal conductivity. The effectiveness of this
      differential measurement technique is demonstrated by measuring thermal
      conductivity of a 200 nm silicon layer. Additionally, this new method enables
      investigation of the accuracy of conventional approaches for extracting sample
      thermal conductivity with the composite beam structure and conventional
      comparative approaches. The results highlight the benefits of the direct
      differential method for accurate measurements with minimal assumptions.

PMID- 28456239
TI  - High-speed microstrip multi-anode multichannel plate detector system.
AB  - High-speed detector systems with high dynamic range and pulse width
      characteristics in the sub-nanosecond regime are mandatory for high resolution
      and highly sensitive time-of-flight mass spectrometers. Typically, for a
      reasonable detector area, an impedance-matched anode design is necessary to
      transmit the registered signal fast and distortion-free from the anode to the
      signal acquisition system. In this report, a high-speed microstrip multi-anode
      multichannel plate detector is presented and discussed. The anode consists of
      four separate active concentric anode segments allowing a simultaneous readout of
      signal with a dynamic range of about eight orders of magnitude. The impedance
      matched anode segments show pulse width of about 250 ps, measured at full width
      at half maximum, and rise time of ~170 ps, measured with an oscilloscope with a
      sampling rate of 20 GS/s and 4 GHz analogue bandwidth. The usage of multichannel
      plates as signal amplifier allowed the design of a lightweight, low power
      consuming, and compact detector system, suitable, e.g., for the integration into
      space instrumentation or portable systems where size, weight, and power
      consumption are limited parameters.

PMID- 28456240
TI  - Note: Coaxial apparatus to measure the permittivities of chemical solutions at
      microwave frequencies.
AB  - Traditional permittivity measurements in microwave chemistry have some
      limitations on bandwidth and probe erosion. To resolve these problems, in this
      note, an apparatus that realizes a real-time wide-band non-contact measurement is
      proposed. Scattering parameters are obtained from measurements made using the
      proposed coaxial apparatus. These parameters are used to reconstruct the
      permittivities of several solutions using artificial neural networks. The maximum
      deviations in measured permittivity at 2.45 and 5.8 GHz are within 5% of results
      from the literature, showing the obvious advantages of coaxial apparatus with
      artificial neural network reconstruction over conventional apparatus.

PMID- 28456241
TI  - Electro-optic correlator for large-format microwave interferometry: Up-conversion
      and correlation stages performance analysis.
AB  - In this paper, a microwave interferometer prototype with a near-infra-red optical
      correlator is proposed as a solution to get a large-format interferometer with
      hundreds of receivers for radio astronomy applications. A 10 Gbits/s Lithium
      Niobate modulator has been tested as part of an electro-optic correlator up
      conversion stage that will be integrated in the interferometer prototype. Its
      internal circuitry consists of a single-drive modulator biased by a SubMiniature
      version A (SMA) connector allowing to up-convert microwave signals with
      bandwidths up to 12.5 GHz to the near infrared band. In order to characterize it,
      a 12 GHz tone and a bias voltage were applied to the SMA input using a
      polarization tee. Two different experimental techniques to stabilize the
      modulator operation point in its minimum optical carrier output power are
      described. The best achieved results showed a rather stable spectrum in amplitude
      and wavelength at the output of the modulator with an optical carrier level 23 dB
      lower than the signal of interest. On the other hand, preliminary measurements
      were made to analyze the correlation stage, using 4f and 6f optical
      configurations to characterize both the antenna/fiber array configuration and the
      corresponding point spread function.

PMID- 28456242
TI  - Monte-Carlo modelling to determine optimum filter choices for sub-microsecond
      optical pyrometry.
AB  - When designing a spectral-band pyrometer for use at high time resolutions (sub
      MUs), there is ambiguity regarding the optimum characteristics for a spectral
      filter(s). In particular, while prior work has discussed uncertainties in
      spectral-band pyrometry, there has been little discussion of the effects of noise
      which is an important consideration in time-resolved, high speed experiments.
      Using a Monte-Carlo process to simulate the effects of noise, a model of
      collection from a black body has been developed to give insights into the optimum
      choices for centre wavelength and passband width. The model was validated and
      then used to explore the effects of centre wavelength and passband width on
      measurement uncertainty. This reveals a transition centre wavelength below which
      uncertainties in calculated temperature are high. To further investigate system
      performance, simultaneous variation of the centre wavelength and bandpass width
      of a filter is investigated. Using data reduction, the effects of temperature and
      noise levels are illustrated and an empirical approximation is determined. The
      results presented show that filter choice can significantly affect instrument
      performance and, while best practice requires detailed modelling to achieve
      optimal performance, the expression presented can be used to aid filter
      selection.

PMID- 28456243
TI  - Measurement of the in-plane thermal conductivity by steady-state infrared
      thermography.
AB  - We demonstrate a simple and quick method for the measurement of the in-plane
      thermal conductance of thin films via steady-state IR thermography. The films are
      suspended above a hole in an opaque substrate and heated by a homogeneous visible
      light source. The temperature distribution of the thin films is captured via
      infrared microscopy and fitted to the analytical expression obtained for the
      specific hole geometry in order to obtain the in-plane thermal conductivity. For
      thin films of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate post-treated
      with ethylene glycol and of polyimide, we find conductivities of 1.0 W m-1 K-1
      and 0.4 W m-1 K-1 at room temperature, respectively. These results are in very
      good agreement with literature values, validating the method developed.

PMID- 28456244
TI  - Inline screw feeding vacuum arc thruster.
AB  - A new type of micropropulsion device for nanosatellite applications is presented
      the inline-screw-feeding vacuum-arc thruster (ISF-VAT). This thruster couples a
      conventional "triggerless" ignition geometry with a feeding mechanism that
      maintains a steady state discharge performance. The feeding mechanism implements
      a screw action on a central cathode rod. At a predetermined rate, a complete and
      uniform erosion of the cathodes tip is obtained as well as "healing" of the
      insulator coating. The inline feeding of the cathode forces the arc to emerge on
      the tip of the cathode, flush with the exit plane of the anode. This enables the
      plasma plume to efficiently accelerate away from the thruster, eliminating the
      need for an additional ion acceleration stage. The ISF-VAT feeding mechanism is
      computer controlled and offers reliable operation of the thruster over a large
      number of pulses. Characterization of the ISF-VAT performance is presented,
      conducted on an experimental prototype in the Aerospace Plasma Laboratory,
      Technion. Measurement results of the mass flow rate, electrical parameters of the
      discharge, and thrust are presented. Using a Ti cathode at a discharge power of 3
      W, a mass flow rate of ~1.8*10-9 kg/s and a thrust level ~ 7 MUN were measured.
      More than 106 pulses were demonstrated in a single run, accumulating a total
      impulse of 0.2 Ns. The thruster prototype dimensions are 15 * 15 * 65 mm3 and are
      ~ 60 g in mass.

PMID- 28456245
TI  - A reconfigurable cryogenic platform for the classical control of quantum
      processors.
AB  - The implementation of a classical control infrastructure for large-scale quantum
      computers is challenging due to the need for integration and processing time,
      which is constrained by coherence time. We propose a cryogenic reconfigurable
      platform as the heart of the control infrastructure implementing the digital
      error-correction control loop. The platform is implemented on a field
      programmable gate array (FPGA) that supports the functionality required by
      several qubit technologies and that can operate close to the physical qubits over
      a temperature range from 4 K to 300 K. This work focuses on the extensive
      characterization of the electronic platform over this temperature range. All
      major FPGA building blocks (such as look-up tables (LUTs), carry chains (CARRY4),
      mixed-mode clock manager (MMCM), phase-locked loop (PLL), block random access
      memory, and IDELAY2 (programmable delay element)) operate correctly and the logic
      speed is very stable. The logic speed of LUTs and CARRY4 changes less then 5%,
      whereas the jitter of MMCM and PLL clock managers is reduced by 20%. The
      stability is finally demonstrated by operating an integrated 1.2 GSa/s analog-to
      digital converter (ADC) with a relatively stable performance over temperature.
      The ADCs effective number of bits drops from 6 to 4.5 bits when operating at 15
      K.

PMID- 28456246
TI  - Energy compression of nanosecond high-voltage pulses based on two-stage hybrid
      scheme.
AB  - Test results of high-voltage subnanosecond pulse generator with a hybrid, two
      stage energy compression scheme are presented. After the first compression
      section with a gas discharger, a ferrite-filled gyromagnetic nonlinear
      transmitting line is used. The offered technical solution makes it possible to
      increase the voltage pulse amplitude from -185 kV to -325 kV, with a 2-ns pulse
      rise time minimized down to ~180 ps. For the small output voltage amplitude of 
      240 kV, the shortest pulse front of ~85 ps was obtained. The generator with
      maximum amplitude was utilized to form an ultra-short flow of runaway electrons
      in air-filled discharge gap with particles' energy approaching to 700 keV.

PMID- 28456247
TI  - An elevated-temperature depth-sensing instrumented indentation apparatus for
      investigating thermo-mechanical behaviour of thermal barrier coatings.
AB  - In our study, an elevated-temperature depth-sensing instrumented indentation
      apparatus was designed and developed to investigate thermo-mechanical response of
      thermal barrier coatings (TBCs). A furnace was used to heat the test region up to
      1600  degrees C and a heat protection design was proposed to protect electronic
      devices from high temperature environment. Load was applied by a precise loading
      motor and a piezoelectric actuator in high (0-440 N) and low (0-40 N) load
      ranges, respectively. A loading shielding scheme was designed to protect the low
      load sensor during the high loading process. In order to obtain reliable test
      data, the as-developed apparatus was calibrated at room and elevated
      temperatures. It is found that the developed apparatus was suitable to obtain the
      intended data. After that, two typical TBCs were tested from 600 to 1500  degrees
      C, and the load-depth curves were presented to show the main functions and
      usability of the measuring system.

PMID- 28456248
TI  - Cold wire constant voltage anemometry to measure temperature fluctuations and its
      application in a thermoacoustic system.
AB  - The knowledge of temperature fluctuations is essential for most thermoacoustic
      systems. In the present paper, cold wire constant-voltage anemometry (CVA) to
      measure temperature fluctuations is presented. Corrections for the thermal
      inertia and for the end losses of the wire are applied during the post
      processing. The correction for the thermal inertia of the cold wire is achieved
      by applying a time dependent thermal lag as proposed originally for a constant
      current anemometry (CCA) system. This thermal lag is measured in parallel by a
      hot wire. The thermal end losses of the wires to their supports are also
      considered and approximate corrections are proposed. The procedure for the cold
      wire CVA is validated in the acoustic field of an acoustic resonator with wires
      of different lengths. A comparison between a CVA and a CCA measurement also
      confirms the CVA measurement. Furthermore, the proposed measurement procedure is
      applied close to the stack of a thermoacoustic refrigerator. Supposing a two
      dimensional flow, the simultaneous measurement of velocity and temperature
      fluctuations is possible. This allows a detailed examination of the acoustic
      field close to the stack, including the study of the correlation between
      temperature and velocity.

PMID- 28456249
TI  - Sputtering of pure boron using a magnetron without a radio-frequency supply.
AB  - Boron at room temperature is insulating and therefore conventionally sputtered
      using radio-frequency power supplies including their power-matching networks. In
      this contribution, we show that through a suitable ignition assistance, via
      temporary application of a high voltage (~600 V) to the substrate holder or
      auxiliary electrode, the magnetron discharge can be ignited using a conventional
      mid-frequency power supply without matching network. Once the discharge is
      ignited, the assisting voltage can be reduced to less than 50 V, and after the
      boron target surface is at elevated temperature, thereby exhibiting sufficient
      conductivity, the assisting voltage can be turned off. The deposition of boron
      and boron nitride films has been demonstrated with a deposition rate of
      approximately 400 nm/h for a power of 250 W.

PMID- 28456250
TI  - Diffraction based method to reconstruct the spectrum of the Thomson scattering x
      ray source.
AB  - As Thomson scattering x-ray sources based on the collision of intense laser and
      relativistic electrons have drawn much attention in various scientific fields,
      there is an increasing demand for the effective methods to reconstruct the
      spectrum information of the ultra-short and high-intensity x-ray pulses. In this
      paper, a precise spectrum measurement method for the Thomson scattering x-ray
      sources was proposed with the diffraction of a Highly Oriented Pyrolytic Graphite
      (HOPG) crystal and was demonstrated at the Tsinghua Thomson scattering X-ray
      source. The x-ray pulse is diffracted by a 15 mm (L) *15 mm (H)* 1 mm (D) HOPG
      crystal with 1 degrees  mosaic spread. By analyzing the diffraction pattern, both
      x-ray peak energies and energy spectral bandwidths at different polar angles can
      be reconstructed, which agree well with the theoretical value and simulation. The
      higher integral reflectivity of the HOPG crystal makes this method possible for
      single-shot measurement.

PMID- 28456251
TI  - High-precision control of static magnetic field magnitude, orientation, and
      gradient using optically pumped vapour cell magnetometry.
AB  - An integrated system of hardware and software allowing precise definition of
      arbitrarily oriented magnetic fields up to |B| = 1 MUT within a five-layer
      Mumetal shield is described. The system is calibrated with reference to magnetic
      resonance observed between Zeeman states of the 6S1/2 F = 4 133Cs ground state.
      Magnetic field definition over the full 4pi solid angle is demonstrated with one
      sigma tolerances in magnitude, orientation, and gradient of delta|B| = 0.94 nT,
      deltatheta = 5.9 mrad, and delta|?B|=13.0 pT/mm, respectively. This field control
      is used to empirically map Mx magnetometer signal amplitude as a function of the
      static field (B0) orientation.

PMID- 28456252
TI  - Edge-preserving reconstruction from sparse projections of limited-angle computed
      tomography using l0-regularized gradient prior.
AB  - Accurate images reconstructed from limited computed tomography (CT) data are
      desired when reducing the X-ray radiation exposure imposed on patients. The total
      variation (TV), known as the l1-norm of the image gradient magnitudes, is popular
      in CT reconstruction from incomplete projection data. However, as the projection
      data collected are from a sparse-view of the limited scanning angular range, the
      results reconstructed by a TV-based method suffer from blocky artifact and
      gradual changed artifacts near the edges, which in turn make the reconstruction
      images degraded. Different from the TV, the l0-norm of an image gradient counts
      the number of its non-zero coefficients of the image gradient. Since the
      regularization based on the l0-norm of the image gradient will not penalize the
      large gradient magnitudes, the edge can be effectively retained. In this work, an
      edge-preserving image reconstruction method based on l0-regularized gradient
      prior was investigated for limited-angle computed tomography from sparse
      projections. To solve the optimization model effectively, the variable splitting
      and the alternating direction method (ADM) were utilized. Experiments
      demonstrated that the ADM-like method used for the non-convex optimization
      problem has better performance than other classical iterative reconstruction
      algorithms in terms of edge preservation and artifact reduction.

PMID- 28456253
TI  - Longitudinally excited N2 laser with large-diameter discharge tube.
AB  - To realize an ultraviolet laser with high beam quality and high output power, we
      are developing a master oscillator power amplifier system for a longitudinally
      excited gas laser. In this system, high beam quality is produced by an oscillator
      stage, and high output power is produced by an amplifier stage. Here, the beam
      profile of the longitudinally excited gas N2 laser had a quasi-Gaussian shape
      when using a large-diameter discharge tube, which enabled the use of the
      amplifier stage. The discharge tube consisted of a dielectric pipe with an inner
      diameter of 14 mm and a length of 30 cm. The discharge tube was covered with a
      metallic tube for pre-ionization. The strength and spatial distribution of pre
      ionization were optimized by adjusting the gap between the metallic tube and the
      discharge tube. The uniform discharge achieved by controlling the pre-ionization
      produced a quasi-Gaussian laser beam profile with a correlation factor of
      0.99513, a laser pulse energy of 343 MUJ, and an input energy of 2.95 J.

PMID- 28456254
TI  - Optothermally actuated capillary burst valve.
AB  - We demonstrate the optothermal actuation of individual capillary burst valves in
      an all-polymer microfluidic device. The capillary burst valves are realised in a
      planar design by introducing a fluidic constriction in a microfluidic channel of
      constant depth. We show that a capillary burst valve can be burst by raising the
      temperature due to the temperature dependence of the fluid surface tension. We
      address individual valves by using a local heating platform based on a thin film
      of near infrared absorber dye embedded in the lid used to seal the microfluidic
      device [L. H. Thamdrup et al., Nano Lett. 10, 826-832 (2010)]. An individual
      valve is burst by focusing the laser in its vicinity. We demonstrate the capture
      of single polystyrene 7 MUm beads in the constriction triggered by the bursting
      of the valve.

PMID- 28456255
TI  - Development of water vapor transmission rate measuring device using a quadrupole
      mass spectrometer and standard gas barrier films down to the 10-6 g m-2 day-1
      level.
AB  - Water vapor transmission rate (WVTR) measuring devices with a quadrupole mass
      spectrometer (QMS) have an advantage in measuring low WVTRs because measurements
      are taken under an extremely low background of water vapor by realizing ultrahigh
      vacuum conditions. Here, the reliability of the QMS measurements was improved by
      including a porous plug with known molecular conductance in the device to
      generate a reference molar flux for in situ QMS calibration. Then, standard gas
      barrier (SGB) films made from a clay-polyimide nanocomposite film were also
      developed and used to validate the measurement. The measurement results for the
      SGB films were on the extrapolated calibration curve obtained with the porous
      plug down to WVTR at the 10-6 g m-2 day-1 level within the estimated measurement
      uncertainty.

PMID- 28456256
TI  - Development of a high-frequency and large-stroke fatigue testing system for
      rubber.
AB  - The limited capabilities of current fatigue testing machines have resulted in
      studies on the fatigue behavior of rubber under large-displacement amplitude and
      high frequency being very sparse. In this study, a fatigue testing system that
      can carry out large-displacement amplitude and high-frequency fatigue tests on
      rubber was developed using a moving magnet voice coil motor (MMVCM) actuator,
      with finite element analysis applied to analyze the thrust of the MMVCM actuator.
      The results of a series of cyclic tension tests conducted on vulcanized natural
      rubber specimens using the developed fatigue testing system verify that it has
      high precision, low noise, large-stroke, and high-frequency characteristics.
      Further, the load frame with the developed MMVCM actuator is feasible for
      material testing, especially for large-stroke and high-frequency fatigue tests.

PMID- 28456257
TI  - Synchronizing single-shot high-energy iodine photodissociation laser PALS and
      high-repetition-rate femtosecond Ti:sapphire laser system.
AB  - A system of precise pulse synchronization between a single-shot large-scale laser
      exploiting an acousto-optical modulator and a femtosecond high repetition rate
      laser is reported in this article. This opto-electronical system has been
      developed for synchronization of the sub-nanosecond kJ-class iodine
      photodissociation laser system (Prague Asterix Laser System-PALS) with the
      femtosecond 25-TW Ti:sapphire (Ti:Sa) laser operating at a repetition rate 1 kHz
      or 10 Hz depending on the required energy level of output pulses. At 1 kHz
      synchronization regime, a single femtosecond pulse of duration about 45 fs and a
      small energy less than 1 mJ are exploited as a probe beam for irradiation of a
      three-frame interferometer, while at 10 Hz repetition rate a single femtosecond
      pulse with higher energy about 7-10 mJ is exploited as a probe beam for
      irradiation of a two-channel polaro-interferometer. The synchronization accuracy
      +/-100 ps between the PALS and the Ti:Sa laser pulses has been achieved in both
      regimes of synchronization. The femtosecond interferograms of laser-produced
      plasmas obtained by the three-frame interferometer and the femtosecond
      polarimetric images obtained by the two-frame polaro-interferometer confirm the
      full usefulness and correct functionality of the proposed method of
      synchronization.

PMID- 28456258
TI  - Comb-locked cavity ring-down saturation spectroscopy.
AB  - We present a new method of comb-locked cavity ring-down spectroscopy for the Lamb
      dip measurement of molecular ro-vibrational transitions. By locking both the
      probe laser frequency and a temperature-stabilized high-finesse cavity to an
      optical frequency comb, we realize saturation spectroscopy of molecules with
      kilohertz accuracy. The technique is demonstrated by recording the R(9) line in
      the upsilon = 3 - 0 overtone band of CO near 1567 nm. The Lamb-dip spectrum of
      such a weak line (transition rate 0.0075 s-1) is obtained using an input laser
      power of only 3 mW, and the position is determined to be 191 360 212 770 kHz with
      an uncertainty of 7 kHz (deltanu/nu~3.5*10-11), which is currently limited by our
      rubidium clock.

PMID- 28456259
TI  - A multichannel visible spectroscopy system for the ITER-like W divertor on EAST.
AB  - To facilitate long-pulse high power operation, an ITER-like actively cooled
      tungsten (W) divertor was installed in Experimental Advanced Superconducting
      Tokamak (EAST) to replace the original upper graphite divertor in 2014. A
      dedicated multichannel visible spectroscopic diagnostic system has been
      accordingly developed for the characterization of the plasma and impurities in
      the W divertor. An array of 22 lines-of-sight (LOSs) provides a profile
      measurement of the light emitted from the plasma along upper outer divertor, and
      the other 17 vertical LOSs view the upper inner divertor, achieving a 13 mm
      poloidal resolution in both regions. The light emitted from the plasma is
      collected by a specially designed optical lens assembly and then transferred to a
      Czerny-Turner spectrometer via 40 m quartz fibers. At the end, the spectra
      dispersed by the spectrometer are recorded with an Electron-Multiplying Charge
      Coupled Device (EMCCD). The optical throughput and quantum efficiency of the
      system are optimized in the wavelength range 350-700 nm. The spectral
      resolution/coverage can be adjusted from 0.01 nm/3 nm to 0.41 nm/140 nm by
      switching the grating with suitable groove density. The frame rate depends on the
      setting of LOS number in EMCCD and can reach nearly 2 kHz for single LOS
      detection. The light collected by the front optical lens can also be divided and
      partly transferred to a photomultiplier tube array with specified bandpass
      filter, which can provide faster sampling rates by up to 200 kHz. The
      spectroscopic diagnostic is routinely operated in EAST discharges with absolute
      optical calibrations applied before and after each campaign, monitoring photon
      fluxes from impurities and H recycling in the upper divertor. This paper presents
      the technical details of the diagnostic and typical measurements during EAST
      discharges.

PMID- 28456260
TI  - Improved design for a low temperature scanning tunneling microscope with an in
      situ tip treatment stage.
AB  - The Low Temperature Scanning Tunneling Microscope (LT-STM) is an extremely
      valuable tool not only in surface science but also in condensed matter physics.
      For years, numerous new ideas have been adopted to perfect LT-STM performances
      Ultra-Low Vibration (ULV) laboratory and the rigid STM head design are among
      them. Here, we present three improvements for the design of the ULV laboratory
      and the LT-STM: tip treatment stage, sample cleaving stage, and vibration
      isolation system. The improved tip treatment stage enables us to perform field
      emission for the purpose of tip treatment in situ without exchanging samples,
      while our enhanced sample cleaving stage allows us to cleave samples at low
      temperature in a vacuum without optical access by a simple pressing motion. Our
      newly designed vibration isolation system provides efficient space usage while
      maintaining vibration isolation capability. These improvements enhance the
      quality of spectroscopic imaging experiments that can last for many days and
      provide increased data yield, which we expect can be indispensable elements in
      future LT-STM designs.

PMID- 28456261
TI  - A star tracker on-orbit calibration method based on vector pattern match.
AB  - On-orbit calibration is aimed at revising the star trackers' measurement model
      parameters and maintaining its attitude accuracy. The performance of existing
      calibration methods is quite poor. Among all the model parameters, the estimation
      of the principal point location is very challenging due to its vulnerability
      against measurement errors, yet, that it is the only parameter depicting the
      optical axis' projecting position on the image plane makes it of great
      significance. Its estimation error adds fixed bias to the output attitudes. Based
      on the criterion of vector pattern match, an on-orbit calibration method is
      proposed. The principal point location is estimated according to the criterion
      first. The other model parameters are updated by maximum likelihood method, and
      measures of multiple succeeding frames optimization and star density weight are
      adopted in the method to guarantee the estimation of robustness. Simulation and
      night sky observation results proved the validity of the proposed method. In the
      simulation with a poor initial guess of the principal point location, novel
      method's result is better than the least square method and Samaan's method.

PMID- 28456262
TI  - Nonmechanical compact probe for cross-sectional velocity measurement based on
      differential laser Doppler velocimetry.
AB  - In this study, we propose and demonstrate a nonmechanical compact probe for cross
      sectional velocity measurement based on differential laser Doppler velocimetry.
      The system introduces a method that combines simultaneous multipoint measurement
      using spatial encoding and nonmechanical scanning of measurement points, in which
      spatially encoded measurement points aligned along the transverse direction are
      scanned in the axial direction by changing the wavelength. The use of a waveguide
      type LiNbO3 phase shifter array for serrodyne frequency shifting is feasible for
      the system based on fiber optics with an easily handled probe. To miniaturize the
      probe, a multimode fiber is introduced in the receiving optics and the parameters
      of the lens system in the transmitting optics are optimized. For the experiment,
      an eight-channel probe was assembled on an aluminum plate with an 8 cm * 8 cm
      area size. The experimental results reveal that the cross-sectional two
      dimensional velocity distribution was successfully measured using the easily
      handled compact probe for the first time.

PMID- 28456263
TI  - Note: Energy calibration of a femtosecond photoelectron imaging detector with
      correction for the ponderomotive shift of atomic ionization energies.
AB  - Femtosecond photoelectron imaging spectroscopy is a powerful technique for
      following state-resolved molecular transformations in complex coupled potential
      energy landscapes. To avoid unwanted nonlinear side-effects, the employed laser
      pulse energies are usually reduced to minimal values. However, the energy
      calibration of the photoelectron imaging detector is ideally performed using
      multi-photon above-threshold ionization of suitable atomic species, for which
      rather high laser intensities are required. In this work, we show that the
      calibration spectra of xenon obtained with high laser pulse energies cannot be
      directly used for the evaluation of molecular photoelectron spectra recorded
      using low-energy laser pulses. The reason is the intensity-dependent AC Stark
      shift of the atomic ionization energies to larger values, which in turn leads to
      a corresponding decrease of the photoelectron kinetic energies. We present a
      simple procedure to quantify this so-called ponderomotive shift and calculate the
      theoretically expected un-shifted photoelectron energies.

PMID- 28456264
TI  - Measurement of fluctuations of electrostatic force acting between a dielectric
      plate and an electrostatic drive.
AB  - A setup for the measurement of the noise associated with the interaction of an
      electrostatic field produced by an electrostatic drive with a fused silica plate
      is presented. The fused silica plate is a part of a 63 Hz high-Q torsional
      oscillator. Its oscillations are measured by an optical interferometric sensor.
      The measurements are PC-controlled and fully automated. A digital post-processing
      scheme is described, allowing the calculation of the plate rotation angle
      fluctuations and the evolution of the charge distribution on the surface of the
      fused silica plate. The characteristic surface charge relaxation time has been
      purposely kept small on the order 103-104 s. The upper limit of the investigated
      noise has been obtained. We used this result to estimate the electrostatic drive
      noise in the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO)
      gravitational wave detector at frequencies of about 18 Hz. The obtained upper
      limit of the strain amplitude spectral density is (1+/-0.13)?10-22Hz-1/2.

PMID- 28456265
TI  - Magnetic cooling for microkelvin nanoelectronics on a cryofree platform.
AB  - We present a parallel network of 16 demagnetization refrigerators mounted on a
      cryofree dilution refrigerator aimed to cool nanoelectronic devices to sub
      millikelvin temperatures. To measure the refrigerator temperature, the thermal
      motion of electrons in a Ag wire-thermalized by a spot-weld to one of the Cu
      nuclear refrigerators-is inductively picked-up by a superconducting gradiometer
      and amplified by a SQUID mounted at 4 K. The noise thermometer as well as other
      thermometers are used to characterize the performance of the system, finding
      magnetic field independent heat-leaks of a few nW/mol, cold times of several days
      below 1 mK, and a lowest temperature of 150 MUK of one of the nuclear stages in a
      final field of 80 mT, close to the intrinsic SQUID noise of about 100 MUK. A
      simple thermal model of the system capturing the nuclear refrigerator, heat
      leaks, and thermal and Korringa links describes the main features very well,
      including rather high refrigerator efficiencies typically above 80%.

PMID- 28456266
TI  - A simple digital control system with field-programmable gate array for
      stabilization of CO2 laser output.
AB  - A simple digital control system was designed to stabilize CO2 laser based on
      digital signal processing with the Field-Programmable Gate Array (FPGA)
      controlling chip and Very-High-Speed Integrated Circuit Hardware Description
      Language program. In this system, the control parameters were easily determined
      by software real-time control, and the control circuit was also designed
      compactly. In addition, the theoretical analysis on the stabilization of CO2
      laser output characteristics was presented based on the photoacoustic effect, and
      the corresponding experiments on the stabilization of CO2 laser output
      characteristics were further performed. The results show that the output power of
      CO2 laser is stabilized at the peak with a relative power stability of 2.71%.
      Furthermore, the frequency of CO2 laser 9P(36) line is stabilized at the center
      of the laser gain curve with a relative stability of (1.57 +/- 0.37)*10-8. This
      system has a potential of further improvements by optimizing the algorithm and
      choosing higher-speed signal processor.

PMID- 28456267
TI  - Influence of sample pool on interference pattern in defocused interferometric
      particle imaging.
AB  - Particles widely exist in various fields. In practical experiments, sometimes it
      is necessary to dissolve particles in water in a sample pool. This article
      proposes two typical layouts of the sample pool in defocused interferometric
      particle imaging (IPI). Layout I is the sample pool surface perpendicular to the
      incident light and layout II is the sample pool surface perpendicular to the
      scattered light. For layout I, the scattered light of the particles does not keep
      symmetric at the meridional and sagittal planes after being refracted by the
      sample pool surface, and elliptical interference patterns are formed at the
      defocused IPI image plane. But for layout II, the scattered light keeps symmetric
      after being refracted, and circular interference patterns are formed. Aimed at
      the two sample pool layouts, the ray-tracing software ZEMAX was used to simulate
      the spot shape of particles at different defocus distances. Furthermore, its
      effect on the ellipticity of the interference pattern with the tilt angle of the
      sample pool is analyzed. The relative error of the axis ratio for layout I does
      not exceed 9.2% at different defocus distances. The experimental results have
      good agreement with the theoretical analyses, and it indicates that layout II is
      more reasonable for the IPI system.

PMID- 28456268
TI  - Note: Manganin foil sensor for small uniaxial stress.
AB  - We describe a simple manganin foil resistance manometer for uniaxial stress
      measurements. The manometer functions at low pressures and over a range of
      temperatures. In this design, no temperature seasoning is necessary although the
      manometer must be prestressed to the upper end of the desired pressure range. The
      prestress pressure cannot be increased arbitrarily; irreversibility arising from
      shear stress limits its range. Attempting larger pressures yields irreproducible
      resistance measurements.

PMID- 28456269
TI  - Invited Review Article: Gas puff imaging diagnostics of edge plasma turbulence in
      magnetic fusion devices.
AB  - Gas puff imaging (GPI) is a diagnostic of plasma turbulence which uses a puff of
      neutral gas at the plasma edge to increase the local visible light emission for
      improved space-time resolution of plasma fluctuations. This paper reviews gas
      puff imaging diagnostics of edge plasma turbulence in magnetic fusion research,
      with a focus on the instrumentation, diagnostic cross-checks, and interpretation
      issues. The gas puff imaging hardware, optics, and detectors are described for
      about 10 GPI systems implemented over the past ~15 years. Comparison of GPI
      results with other edge turbulence diagnostic results is described, and many
      common features are observed. Several issues in the interpretation of GPI
      measurements are discussed, and potential improvements in hardware and modeling
      are suggested.

PMID- 28456270
TI  - A gas aggregation source for the production of heterogeneous molecular clusters.
AB  - We present the design of a versatile gas aggregation source that allows producing
      molecular beams of charged clusters containing a controlled amount of chosen
      impurities. Several examples of clusters production using this source
      characterized by time of flight mass spectrometry are presented here. We
      demonstrate the source ability to produce homogeneous clusters, such as pure
      protonated water and alcohol clusters, as well as inhomogeneous ones such as
      water clusters containing a few units of uracil, glycine, sulfuric acid, or
      pyrene.

PMID- 28456271
TI  - Determination of the resistivity anisotropy of orthorhombic materials via
      transverse resistivity measurements.
AB  - Measurements of the resistivity anisotropy can provide crucial information about
      the electronic structure and scattering processes in anisotropic and low
      dimensional materials, but quantitative measurements by conventional means often
      suffer very significant systematic errors. Here we describe a novel approach to
      measuring the resistivity anisotropy of orthorhombic materials, using a single
      crystal and a single measurement that is derived from a pi4 rotation of the
      measurement frame relative to the crystallographic axes. In this new basis, the
      transverse resistivity gives a direct measurement of the resistivity anisotropy,
      which combined with the longitudinal resistivity also gives the in-plane elements
      of the conventional resistivity tensor via a 5-point contact geometry. This is
      demonstrated through application to the charge-density wave compound ErTe3, and
      it is concluded that this method presents a significant improvement on existing
      techniques, particularly when measuring small anisotropies.

PMID- 28456273
TI  - High-pressure rotational deformation apparatus to 135 GPa.
AB  - A large-strain, torsional deformation apparatus has been developed based on
      diamond anvil cells at high pressures, up to 135 GPa with a help of hard nano
      polycrystalline diamond anvils. These pressure conditions correspond to the base
      of the Earth's mantle. An X-ray laminography technique is introduced for high
      pressure in situ 3D observations of the strain markers. The technique developed
      in this study introduces the possibility of the in situ rheological measurements
      of the deep Earth materials under ultrahigh-pressure conditions.

PMID- 28456274
TI  - A specific absorption rate reduction method for simultaneous multislice magnetic
      resonance imaging.
AB  - This study proposes a modified Shinnar-Le Roux method to synthesize the
      excitation radio frequency (RF) pulse for a 2D gradient echo (GRE) based
      simultaneous multi-slice (SMS) magnetic resonance imaging (MRI) with features of
      low specific absorption rate (SAR) and small out-of-slice ripple. This synthesis
      method for SMS RF pulses employs thinner slice bandwidth and lower multislice
      offset frequencies to reduce SAR values and adopts a weighted Parks-McClellan
      algorithm to reduce sidelobes. Formulas for estimating relative SAR values of the
      SMS pulses are also introduced. Relative SAR values and out-of-slice ripples of
      the proposed and typical RF pulses with different parameters are presented. In
      simultaneous 5-slice phantom and 3-slice human brain imaging, SMS pulses
      synthesized with the proposed method achieve 32% and 28% SAR values of standard
      pulses while providing similar image qualities. Typical RF pulses such as sinc x
      cos can also take advantage of the proposed method and offer lower SAR values for
      SMS imaging. The RF pulse synthesized using the proposed method features low SAR,
      small sidelobes, and consistent image quality for 2D GRE-based SMS MRI. This
      method is applicable to the synthesis of typical SMS RF pulses for significant
      SAR reduction.

PMID- 28456275
TI  - Instrumentation and control of harmonic oscillators via a single-board
      microprocessor-FPGA device.
AB  - We report the development of an instrumentation and control system instantiated
      on a microprocessor-field programmable gate array (FPGA) device for a harmonic
      oscillator comprising a portion of a magnetic resonance force microscope. The
      specific advantages of the system are that it minimizes computation, increases
      maintainability, and reduces the technical barrier required to enter the
      experimental field of magnetic resonance force microscopy. Heterodyne digital
      control and measurement yields computational advantages. A single microprocessor
      FPGA device improves system maintainability by using a single programming
      language. The system presented requires significantly less technical expertise to
      instantiate than the instrumentation of previous systems, yet integrity of
      performance is retained and demonstrated with experimental data.

PMID- 28456276
TI  - Recent developments in machine learning for medical imaging applications.

PMID- 28456277
TI  - Corrigendum to "Cross reactive molecules of human lymphatic filaria Brugia malayi
      inhibit Leishmania donovani infection in hamsters" [Acta Trop. 152 (2015) 103
      111].

PMID- 28456278
TI  - Metal-enhanced luminescence: Current trend and future perspectives- A review.
AB  - Optically enhanced biosensing strategies are prerequisites for developing
      miniature and highly sensitive multiplexed analytical platforms. Such smart
      biosensing systems are highly promising for use in the fields of biomedicine and
      environmental monitoring. Optical signal enhancement during bioassays is
      attributed to the complex opto-electronic interactions of incoming photonic
      signals at the nanomaterial interface. Research on the use of metals other than
      gold and silver for such purposes tends to extend the spectral window to observe
      luminescence enhancement effects. Such manifold increase in luminescence may be
      explained by the principles of plasmon coupling, directional emission led high
      collection efficiency, Rayleigh scattering and related opto-electronic events.
      The present review begins with a mechanistic description of important phenomena
      associated with metal-induced luminescence enhancement, particularly focusing on
      the origin of metal-enhanced luminescence. This review further analyses the
      hybrid nanostructure capabilities responsible for maintaining unique opto
      electronic properties during bio-functionalisation. Current research trends in
      this area, future scope of this field for designing useful bioassays and
      concluding remarks are then discussed.

PMID- 28456279
TI  - Calibration transfer of a Raman spectroscopic quantification method from at-line
      to in-line assessment of liquid detergent compositions.
AB  - The industrial production of liquid detergent compositions entails delicate
      balance of ingredients and process steps. In order to assure high quality and
      productivity in the manufacturing line, process analytical technology tools such
      as Raman spectroscopy are to be implemented. Marked chemical specificity,
      negligible water interference and high robustness are ascribed to this process
      analytical technique. Previously, at-line calibration models have been developed
      for determining the concentration levels of the being studied liquid detergents
      main ingredients from Raman spectra. A strategy is now proposed to transfer such
      at-line developed regression models to an in-line set-up, allowing real-time
      dosing control of the liquid detergent composition under production. To mimic in
      line manufacturing conditions, liquid detergent compositions are created in a
      five-liter vessel with an overhead mixer. Raman spectra are continuously acquired
      by pumping the detergent under production via plastic tubing towards a Raman
      superhead probe, which is incorporated into a metal frame with a sapphire window
      facing the detergent fluid. Two at-line developed partial least squares (PLS)
      models are aimed at transferring, predicting the concentration of surfactant 1
      and polymer 2 in the examined liquid detergent composition. A univariate
      slope/bias correction (SBC) is investigated, next to three well-acknowledged
      multivariate transformation methods: direct, piecewise and double-window
      piecewise direct standardization. Transfer is considered successful when the
      magnitude of the validation sets root mean square error of prediction (RMSEP) is
      similar to or smaller than the corresponding at-line prediction error. The
      transferred model offering the most promising outcome is further subjected to an
      exhaustive statistical evaluation, in order to appraise the applicability of the
      suggested calibration transfer method. Interval hypothesis tests are thereby
      performed for method comparison. It is illustrated that the investigated transfer
      approach yields satisfactory results, provided that the original at-line
      calibration model is thoroughly validated. Both SBC transfer models return lower
      RMSEP values than their corresponding original models. The surfactant 1 assay met
      all relevant evaluation criteria, demonstrating successful transfer to the in
      line set-up. The in-line quantification of polymer 2 levels in the liquid
      detergent composition could not be statistically validated, due to the poorer
      performance of the at-line model.

PMID- 28456280
TI  - Ultrasensitive electrochemical biosensor based on the oligonucleotide self
      assembled monolayer-mediated immunosensing interface.
AB  - Highly sensitive and selective quantitation of a variety of proteins over a wide
      concentration range is highly desirable for increased accuracy of biomarker
      detection or for multidisease diagnostics. In the present contribution, using
      human immunoglobulin G (HIgG) as the model target protein, an electrochemical
      ultrasensitive immunosensing platform was developed based on the oligonucleotide
      self-assembled monolayer-mediated (OSAM) sensing interface. For this
      immunosensor, the "signal-on" signaling mechanism and enzymatic signal
      amplification effect were integrated into one sensing architecture. Moreover, the
      thiolated flexible single-stranded DNAs immobilized onto gold electrode surface
      not only performs the wobbling motion to facilitate the electron transfer between
      the electrode surface and biosensing layer but also fundamentally prohibiting the
      direct interaction of proteins with gold substrate. Thus, the electrochemical
      signal could be efficiently enhanced and the unspecific adsorption or cross
      reaction might be eliminated. As a result, utilizing the newly-proposed
      immunosensor, the HIgG can be detected down to 0.5 ng/mL, and the high detection
      specificity is offered. The successful design of OSAM and the highly desirable
      detection capability of new immunosensor are expected to provide a perspective
      for fabricating new robust immunosensing platform and for promising potential of
      oligonucleotide probe in biological research and biomedical diagnosis.

PMID- 28456281
TI  - Redox cycling-based immunoassay for detection of carcinogenic embryonic antigen.
AB  - Redox cycling based on an interdigitated electrode (IDE) was used as a highly
      sensitive immunoassay for carcinogenic embryonic antigen (CEA) through the
      quantification of 3,3',5,5'-tetramethylbenzidine (TMB). For the redox cycling
      process, one pair of interdigitated finger electrodes was used as the first
      working electrode (generator) for cyclic voltammetry of TMB, and another pair of
      interdigitated finger electrodes was used as the second working electrode
      (collector) for sequential application of potentials for reduction and oxidation
      of TMB. The reduction (and oxidation) products of TMB at the collector were
      supplied to the generator, and following sequential oxidization (and reduction)
      at the generator, again supplied to the collector. Such redox recycling processes
      between the generator and collector allowed signal amplification. In this work,
      the influences of the following factors on the redox cycling of TMB were
      analyzed: (1) the redox potential at the collector, (2) the gap between the
      interdigitated finger electrodes, and (3) the scan rate of the generator. The
      redox potential and electrode gap influences were simulated with COMSOL software
      and compared with empirical results. At the optimum redox potentials and
      electrode gap, redox cycling was estimated to be five-fold more sensitive for the
      quantification of TMB than conventional cyclic voltammetry using one pair of
      interdigitated finger electrodes as the working electrode. Finally, redox cycling
      was applied to a commercial immunoassay for CEA, and the sensitivity of redox
      cycling was three-fold higher than that of conventional cyclic voltammetry using
      a single set of interdigitated finger electrodes as the working electrode.

PMID- 28456282
TI  - Magnetic headspace adsorptive extraction of chlorobenzenes prior to thermal
      desorption gas chromatography-mass spectrometry.
AB  - This study presents a new, user-friendly, cost-effective and portable headspace
      solid-phase extraction technique based on graphene oxide decorated with iron
      oxide magnetic nanoparticles as sorbent, located on one end of a small neodymium
      magnet. Hence, the new headspace solid-phase extraction technique has been called
      Magnetic Headspace Adsorptive Extraction (Mag-HSAE). In order to assess Mag-HSAE
      technique applicability to model analytes, some chlorobenzenes were extracted
      from water samples prior to gas chromatography-mass spectrometry determination. A
      multivariate approach was employed to optimize the experimental parameters
      affecting Mag-HSAE. The method was evaluated under optimized extraction
      conditions (i.e., sample volume, 20 mL; extraction time, 30 min; sorbent amount,
      10 mg; stirring speed, 1500 rpm, and ionic strength, non-significant), obtaining
      a linear response from 0.5 to 100 ng L-1 for 1,3-DCB, 1,4-DCB, 1,2-DCB, 1,3,5
      TCB, 1,2,4-TCB and 1,2,3-TCB; from 0.5 to 75 ng L-1 for 1,2,4,5-TeCB, and PeCB;
      and from 1 to 75 ng L-1 for 1,2,3,4-TeCB. The repeatability of the proposed
      method was evaluated at 10 ng L-1 and 50 ng L-1 spiking levels, and coefficients
      of variation ranged between 1.5 and 9.5% (n = 5). Limits of detection values were
      found between 93 and 301 pg L-1. Finally, tap, mineral and effluent water were
      selected as real water samples to assess method applicability. Relative
      recoveries varied between 86 and 110% showing negligible matrix effects.

PMID- 28456283
TI  - Fabrication of a polymeric composite incorporating metal-organic framework
      nanosheets for solid-phase microextraction of polycyclic aromatic hydrocarbons
      from water samples.
AB  - In this contribution, it was discovered that even distribution of a metal-organic
      framework (MOF) [e.g. copper 1,4-benzenedicarboxylate (CBDC)] within polymeric
      matrixes (e.g. polyimide) resulted in a high-efficient coating material on the
      surface of a stainless steel wire (SSW). Consequently, a home-made solid phase
      microextraction (SPME) fiber was fabricated for fast determination of target
      analytes in real water samples. Scanning electron microscope images indicated
      that the coating possessed homogenously porous surface. Coupled with gas
      chromatography-mass spectrometry (GC-MS) and direct immersion SPME (DI-SPME)
      technique, the fiber was evaluated through the analysis of five polycyclic
      aromatic hydrocarbons (PAHs) in aqueous samples. Under optimized extraction and
      desorption conditions, the established method based on the home-made fiber
      exhibited good repeatability (4.2-12.7%, n = 6) and reproducibility (0.9-11.7%, n
      = 3), low limits of detection (LODs, 0.11-2.10 ng L-1), low limits of
      quantification (LOQs, 0.36-6.99 ng L-1) and wide linear ranges (20-5000 ng L-1).
      Eventually, the method was proven applicable in the determination of PAHs in real
      samples, as the recoveries were in a satisfactory range (81.7-116%).

PMID- 28456284
TI  - Resolution of isomeric new designer stimulants using gas chromatography - Vacuum
      ultraviolet spectroscopy and theoretical computations.
AB  - Distinguishing isomeric representatives of "bath salts", "plant food", "spice",
      or "legal high" remains a challenge for analytical chemistry. In this work, we
      used vacuum ultraviolet spectroscopy combined with gas chromatography to address
      this issue on a set of forty-three designer drugs. All compounds, including many
      isomers, returned differentiable vacuum ultraviolet/ultraviolet spectra. The pair
      of 3- and 4-fluoromethcathinones (m/z 181.0903), as well as the
      methoxetamine/meperidine/ethylphenidate (m/z 247.1572) triad, provided very
      distinctive vacuum ultraviolet spectral features. On the contrary, spectra of 4
      methylethcathinone, 4-ethylmethcathinone, 3,4-dimethylmethcathinone triad (m/z
      191.1310) displayed much higher similarities. Their resolution was possible only
      if pure standards were probed. A similar situation occurred with the ethylone and
      butylone pair (m/z 221.1052). On the other hand, majority of forty-three drugs
      was successfully separated by gas chromatography. The detection limits for all
      the drug standards were in the 2-4 ng range (on-column amount), which is
      sufficient for determinations of seized drugs during forensics analysis. Further,
      state-of-the-art time-dependent density functional theory was evaluated for
      computation of theoretical absorption spectra in the 125-240 nm range as a
      complementary tool.

PMID- 28456285
TI  - Using precursor ion scan of 184 with liquid chromatography-electrospray
      ionization-tandem mass spectrometry for concentration normalization in cellular
      lipidomic studies.
AB  - Cellular lipidomic studies have been favored approaches in many biomedical
      research areas. To provide fair comparisons of the studied cells, it is essential
      to perform normalization of the determined concentration before lipidomic
      analysis. This study proposed a cellular lipidomic normalization method by
      measuring the phosphatidylcholine (PC) and sphingomyelin (SM) contents in cell
      extracts. To provide efficient analysis of PC and SM in cell extracts, flow
      injection analysis-electrospray ionization-tandem mass spectrometry (FIA-ESI
      MS/MS) with a precursor ion scan (PIS) of m/z 184 was used, and the parameters
      affecting the performance of the method were optimized. Good linearity could be
      observed between the cell extract dilution factor and the reciprocal of the total
      ion chromatogram (TIC) area in the PIS of m/z 184 within the dilution range of 1-
      to 16-fold (R2 = 0.998). The calibration curve could be used for concentration
      adjustment of the unknown concentration of a cell extract. The intraday and
      intermediate precisions were below 10%. The accuracy ranged from 93.0% to 105.6%.
      The performance of the new normalization method was evaluated using different
      numbers of HCT-116 cells. Sphingosine, ceramide (d18:1/18:0), SM (d18:1/18:0) and
      PC (16:1/18:0) were selected as the representative test lipid species, and the
      results showed that the peak areas of each lipid species obtained from different
      cell numbers were within a 20% variation after normalization. Finally, the PIS of
      184 normalization method was applied to study ischemia-induced neuron injury
      using oxygen and glucose deprivation (OGD) on primary neuronal cultured cells.
      Our results showed that the PIS of 184 normalization method is an efficient and
      effective approach for concentration normalization in cellular lipidomic studies.

PMID- 28456286
TI  - Catalyst-free "click" functionalization of polymer brushes preserves antifouling
      properties enabling detection in blood plasma.
AB  - Progress in biosensors for clinical detection critically relies on modifications
      of the transducer surface to prevent non-specific adsorption from matrix
      components (i.e. antifouling) while supporting biomolecular recognition elements
      to capture the analyte. Such combination of properties presents a significant
      challenge. Hierarchically structured polymer brushes comprising an antifouling
      polymer bottom block and a functionalizable top block are proposed as a promising
      strategy to achieve this goal. We employed the catalyst-free strain-promoted
      alkyne-azide cycloaddition (SPAAC) "click" reaction to biofunctionalize
      antifouling polymer brushes without impairing their resistance to fouling. The
      functionalization was performed on the side chains along the top polymer block or
      only on the end-groups of the polymer brush. The immobilized amounts of
      bioreceptors (streptavidin followed by biotin-conjugated proteins) and the
      resistance to fouling from blood plasma of the surfaces obtained were evaluated
      via surface plasmon resonance. The end group functionalization approach resulted
      in very low immobilization of bioreceptor. On the other hand, the side group
      modification of a top polymer block led to immobilization of 83% of a monolayer
      of streptavidin. Following binding of a biotin-conjugated antibody (66 ng cm-2)
      the functionalized layer was able to reduce the fouling from undiluted human
      blood plasma by 89% in comparison with bare gold. Finally, the functionalized
      hierarchical polymer brushes were applied to the label-free detection of a model
      analyte in diluted human blood plasma, highlighting the potential for translation
      to medical applications.

PMID- 28456287
TI  - Bimetallic Bi/Pt peroxidase mimic and its bioanalytical applications.
AB  - In this work, bimetallic Bi/Pt nanoparticles in bovine serum albumin biomolecular
      scaffold (BSA-Bi/PtNPs) were synthesized through a facile and green method. As
      compared with BSA-PtNPs, the BSA-Bi/PtNPs possess enhanced peroxidase-like
      catalytic activity. Moreover, the BSA-Bi/PtNPs are stable in harsh conditions
      such as high temperature, extreme pH environments, and high ionic strength, as
      well as in common biological matrixes. These prominent advantages enable the BSA
      Bi/PtNPs to be applied to a wide range of fields. Bioassays, such as serum
      glucose detection, extracellular hydrogen peroxide (H2O2) monitor, and cancer
      cells labeling, have been realized with satisfying results. The linear range of
      glucose determination was from 1 to 100 MUM and the limit of detection (LOD) was
      0.2 MUM. The H2O2 released from each MCF-7 cell after stimulation was calculated
      to be 2.66 * 10-16 mol/s. By utilizing folic acid as a recognition element, tumor
      cell could be readily distinguished by BSA-Bi/PtNPs and the LOD for MCF-7 cell
      detection was 90 cells.

PMID- 28456288
TI  - New perspectives for Advanced Oxidation Processes.
AB  - Advanced Oxidation Processes (AOPs) are called to fill the gap between the
      treatability attained by conventional physico-chemical and biological treatments
      and the day-to-day more exigent limits fixed by environmental regulations. They
      are particularly important for the removal of anthropogenic pollutants and for
      this reason, they have been widely investigated in the last decades and even
      applied in the treatment of many industrial wastewater flows. However, despite
      the great development reached, AOPs cannot be considered mature yet and there are
      many new fields worthy of research. Some of them are going to be briefly
      introduced in this paper, including hybrid processes, heterogeneous semiconductor
      photocatalysis, sulphate-radical oxidation and electrochemical advanced oxidation
      for water/wastewater treatment. Moreover, the use of photoelectrochemical
      processes for energy production is discussed. The work ends with some
      perspectives that can be of interest for the ongoing and future research.

PMID- 28456289
TI  - Engineering and delivery of nanocolloids of hydrophobic drugs.
AB  - A lot of efforts have been devoted to engineering the delivery of hydrophobic
      drugs due to the high demand of chemotherapy against cancer. While early
      developed liposomes and polymeric nanoparticles did not meet the requirements of
      high drug loading efficiency, pure drug nanoparticles appeared to meet these
      together with high stability. Current drug delivery systems demand an improved
      performance over the whole aspects of stability, loading capacity, and
      therapeutic effects. As a result, both new techniques based on traditional
      methods and totally new procedures are under investigation. In this review, we
      focus on the evaluation of pure drug nanolloids fabricated by different
      engineering protocols with emphasis on the size and morphology, delivery and
      controlled release, and therapeutic effects of these drug nanocolloids.

PMID- 28456290
TI  - The great curve: statistics and psychiatry.

PMID- 28456291
TI  - NMDAR antibodies in first episode psychosis: conclusions too inflammatory given
      results?

PMID- 28456292
TI  - NMDAR antibodies in first episode psychosis: conclusions too inflammatory given
      results? - Authors' reply.

PMID- 28456293
TI  - Firearm lobbying, suicide prevention, and the Trump presidency.

PMID- 28456295
TI  - Shekhar Saxena.

PMID- 28456296
TI  - The long walk home: trauma psychiatry on film.

PMID- 28456297
TI  - Grey.

PMID- 28456298
TI  - Identification of a trichothecene production inhibitor by chemical array and
      library screening using trichodiene synthase as a target protein.
AB  - Trichothecene mycotoxins often accumulate in apparently normal grains of cereal
      crops. In an effort to develop an agricultural chemical to reduce trichothecene
      contamination, we screened trichothecene production inhibitors from the compounds
      on the chemical arrays. By using the trichodiene (TDN) synthase tagged with
      hexahistidine (rTRI5) as a target protein, 32 hit compounds were obtained from
      chemical library of the RIKEN Natural Product Depository (NPDepo) by chemical
      array screening. At 10MUgmL-1, none of the 32 chemicals inhibited trichothecene
      production by Fusarium graminearum in liquid culture. Against the purified rTRI5
      enzyme, however, NPD10133 [progesterone 3-(O-carboxymethyl)oxime amide-bonded to
      phenylalanine] showed weak inhibitory activity at 10MUgmL-1 (18.7MUM). For the
      screening of chemicals inhibiting trichothecene accumulation in liquid culture,
      20 analogs of NPD10133 selected from the NPDepo chemical library were assayed. At
      10MUM, only NPD352 [testosterone 3-(O-carboxymethyl)oxime amide-bonded to
      phenylalanine methyl ester] inhibited rTRI5 activity and trichothecene
      production. Kinetic analysis suggested that the enzyme inhibition was of a mixed
      type. The identification of NPD352 as a TDN synthase inhibitor lays the
      foundation for the development of a more potent inhibitor via systematic
      introduction of wide structural diversity on the gonane skeleton and amino acid
      residues.

PMID- 28456299
TI  - Molecular and biochemical characterization of dimethachlone resistant isolates of
      Sclerotinia sclerotiorum.
AB  - Sclerotinia sclerotiorum is a necrotrophic fungal plant pathogen with a broad
      host range. The dicarboximide fungicide dimethachlone has been used to control
      this pathogen for more than a decade and resistance to dimethachlone has recently
      been reported in China. Compared with sensitive isolates, the three dimethachlone
      resistant isolates with resistance ratios of 78.3, 85.5, and 94.8 exhibited
      significantly (P<0.05) higher cell membrane permeability and peroxidase and
      polyphenol oxidase activities. Dimethachlone at 0.25MUg/mL significantly
      increased cell membrane permeability and enhanced activity of the two enzymes in
      both resistant and sensitive isolates. There were no significant differences in
      glycerol or oxalate content between the resistant and sensitive isolates.
      Dimethachlone treatment increased glycerol content in the resistant isolates and
      reduced in the sensitive isolates (P<0.01). Sequencing of three genes involved in
      two-component signal pathway and of three genes in mitogen-activated protein
      (MAP) kinase cascade demonstrated that the dimethachlone resistant isolates HLJ4
      and HLJ6 harbored point mutations of I232T and G1087D, respectively, in the
      deduce amino acid sequence of the histidine kinase (HK) gene Sshk. HLJ4 had a
      point mutation of P96L in the deduced amino acid sequence of the MAP kinase
      kinase gene SsPbs. The expression levels of the Sshk gene were higher in HLJ4 and
      HLJ6 than in HLJ3 and the sensitive isolate HLJMG2, and transcription of the Sshk
      gene was up-regulated by dimethachlone for the three resistant isolates.

PMID- 28456300
TI  - Isoxadifen safening mechanism in sweet corn genotypes with differential response
      to P450-metabolized herbicides.
AB  - Three sweet corn genotypes, two inbred lines (IBER001 and IBER002) and their
      hybrid (ER00X), differ in their phenotypic responses to several P450-metabolized
      herbicides, used in sweet corn, namely, foramsulfuron, iodosulfuron, rimsulfuron
      and tembotrione. Foramsulfuron is a sulfonylurea herbicide commonly formulated
      with the safener isoxadifen that is used for selective post-emergence weed
      control in corn. Our goal was to elucidate the mechanism of these genotypes'
      responses to foramsulfuron and safener isoxadifen and examine the heritability of
      those responses. IBER001 was sensitive to foramsulfuron+isoxadifen, with an ED50
      of 3.6gaiha-1, while IBER002 and ER00X were tolerant with ED50 values of 808 and
      700gaiha-1, respectively. ALS enzyme extracted from each of the different
      genotypes was equally sensitive to foramsulfuron. Pre-treatment with malathion, a
      known cytochrome P450 inhibitor, increased foramsulfuron injury in IBER002 and
      ER00X, but had no effect on those lines when isoxadifen was applied with the
      herbicide. Foramsulfuron-treated IBER001 was severely injured regardless of the
      presence of malathion and/or isoxadifen. Pre-treatment with malathion similarly
      increased the phytotoxicity of iodosulfuron+safener (mefenpyr) and rimsulfuron to
      the tolerant genotypes, but did not increase the level of injury caused by the
      tembotrione+isoxadifen treatment. Segregation of F2 and backcross progenies
      according to their responses to foramsulfuron+isoxadifen revealed a pattern of
      inheritance typical of a trait controlled by a single gene inheritance, with a
      recessive allele conferring sensitivity. Our results support the hypothesis that
      foramsulfuron selectivity is associated with P450 metabolism and that isoxadifen
      positively affects P450 activity. The sensitive genotype that does not respond to
      isoxadifen is presumably homozygous for a deficient or non-functioning P450 gene.

PMID- 28456301
TI  - Monitoring of antivitamin K-dependent anticoagulation in rodents - Towards an
      evolution of the methodology to detect resistance in rodents.
AB  - Vitamin K antagonists are used as rodenticides for pest control management. In
      rodents, prothrombin time is used to monitor their effect despite its limits and
      the emergence of many coagulation methods. The aim of this study is to explore
      different coagulation monitoring methods in order to propose the best method and
      the best parameter to monitor vitamin K antagonists effect in rodents. The
      coagulation function was thus monitored with global coagulation assays and
      specialty assays after difethialone administration in rats. Despite many
      parameters obtained by thromboelastometry, only clotting time and clot formation
      time obtained by ExTEM were modified. Their evolution was fast with doubling time
      respectively of 4.0h and 3.7h but their increases were delayed with a lag time
      higher than 8h. Conversely, prothrombin time evolution presented a lag time of
      only 2h, but a higher doubling time of 7.2h. The measurements of factor VII and X
      activities were the most sensitive assays to monitor vitamin K antagonists effect
      with almost no lag time and the fastest evolution. Nevertheless, factor X was
      shown to be the only key factor driving prothrombin time. Monitoring factor X
      activity enables to follow most effectively the anticoagulation status in rats
      after rodenticides administration.

PMID- 28456302
TI  - Label-free quantitative proteomic analysis of inhibition of Xanthomonas
      axonopodis pv. citri by the novel bactericide Fubianezuofeng.
AB  - To understand the antibacterial mechanism of the new bactericide 2
      (methylsulfonyl)-5- (4-fluorobenzyl)-1, 3, 4-oxadiazole (Generic name:
      Fubianezuofeng), we performed label-free quantitative proteomics analysis of the
      response of Xanthomonas axonopodis pv. citri (Xac) strain 29-1 to Fubianezuofeng.
      A total of 1133 proteins were identified in the treatment and control groups.
      Upon treatment with the 1/2 minimum inhibitory concentration (MIC), 339 proteins
      were found to be differentially expressed (fold changes>1.5, p<0.05) with 99
      upregulated and 240 down-regulated. In comparison, 314 proteins were
      differentially expressed (125 up-regulated, 189 down-regulated) at MIC. The
      differentially expressed proteins were enriched for those involved in the
      pyrimidine metabolic pathway. The results offer a complete view of the proteome
      changes in bacteria in response to Fubianezuofeng.

PMID- 28456303
TI  - Antioxidant enzymes and their role in phoxim and carbaryl stress in
      Caenorhabditis elegans.
AB  - Pesticide exposure can induce oxidative stress and cause changes to antioxidant
      enzymes in living organisms. In the present study, the effects of phoxim (an
      organophosphorus insecticide) and carbaryl (a carbamate insecticide) on
      antioxidant enzyme activity and gene expression were investigated in the model
      organism Caenorhabditis elegans. The results show that phoxim exposure can induce
      superoxide dismutase (SOD) and catalase (CAT) activities and decrease glutathione
      peroxidase (GPx) activity at lower concentrations. The expression levels of sod
      3, sod-5, ctl-1, gpx-6, and gpx-8 were up-regulated after treatment with phoxim.
      The mRNA expression levels of sod-5, ctl-1 and gpx-6 were increased approximately
      70-, 170- and 130-fold, respectively, in the 0.25mM treatment group compared to
      the control group. Carbaryl exposure decreased SOD activity and induced CAT and
      GPx activities. The addition of carbaryl up-regulated the expression of sod-5,
      ctl-1, ctl-3 and gpx-8. Specifically, ctl-1 expression increased approximately 10
      fold, and gpx-8 expression increased <30-fold in the 0.5mM treatment group
      relative to the control group. The transcript level of sod-5 increased >20-fold,
      and ctl-3 increased approximately 10-fold in the 1mM treatment group. The
      functions of the antioxidant enzymes during oxidative stress caused by the two
      insecticides were investigated using deletion mutants. The LC50 values phoxim for
      the of sod-3 (tm760), sod-5 (tm1146), ctl-1 (ok1242), ctl-3 (ok2042) and gpx-8
      (tm2108) mutant strains were lower than those observed for the N2 strain. The
      LC50 values of carbaryl for the ctl-1 (ok1242), ctl-3 (ok2042) and gpx-6 (tm2535)
      deletion mutant strains decreased in comparison to the N2 strain. The results
      suggest that these two insecticides caused oxidative stress and changed altered
      the antioxidant enzyme activities and their gene expressions in C. elegans. The
      sod-3, sod-5, ctl-1, ctl-3, gpx-6, and gpx-8 encoding enzymes may play roles in
      defending cells from oxidative stress caused by these two insecticides.

PMID- 28456304
TI  - CYP6B6 is involved in esfenvalerate detoxification in the polyphagous
      lepidopteran pest, Helicoverpa armigera.
AB  - The cotton bollworm, Helicoverpa armigera, is a polyphagous pest that has a
      strong capacity to evolve resistance against various classes of insecticides.
      Cytochrome P450 enzymes have been suspected involved in pyrethroid metabolism and
      resistance in this pest. However, how many and which P450s are involved in
      pyrethroid metabolism is largely unknown. In this study, CYP6B6 and NADPH
      cytochrome P450 reductase (HaCPR) from H. armigera were successfully co-expressed
      in Escherichia coli. Incubation of esfenvalerate with the recombinant CYP6B6
      HaCPR monooxygenase complex revealed that CYP6B6 was able to transform
      esfenvalerate into 4'-hydroxy fenvalerate. Kcat and Km values for the formation
      of 4'-hydroxyfenvalerate by the E. coli-produced CYP6B6 were determined to be
      1.65+/-0.11min-1 and 4.10+/-0.84MUM respectively. Our results demonstrate that
      CYP6B6 has the ability to hydroxylate esfenvalerate, thus plays a role in
      fenvalerate detoxification.

PMID- 28456305
TI  - Target-site and non-target-site resistance mechanisms to ALS inhibiting
      herbicides in Papaver rhoeas.
AB  - Target-site and non-target-site resistance mechanisms to ALS inhibitors were
      investigated in multiple resistant (tribenuron-methyl and 2,4-D) and only 2,4-D
      resistant, Spanish corn poppy populations. Six amino-acid replacements at the
      Pro197 position (Ala197, Arg197, His197, Leu197, Thr197 and Ser197) were found in
      three multiple resistant populations. These replacements were responsible for the
      high tribenuron-methyl resistance response, and some of them, especially Thr197
      and Ser197, elucidated the cross-resistant pattern for imazamox and florasulam,
      respectively. Mutations outside of the conserved regions of the ALS gene (Gly427
      and Leu648) were identified, but not related to resistance response. Higher
      mobility of labeled tribenuron-methyl in plants with multiple resistance was,
      however, similar to plants with only 2,4-D resistance, indicating the presence of
      non-target-site resistance mechanisms (NTSR). Metabolism studies confirmed the
      presence of a hydroxy imazamox metabolite in one of the populations. Lack of
      correlation between phenotype and genotype in plants treated with florasulam or
      imazamox, non-mutated plants surviving imazamox, tribenuron-methyl translocation
      patterns and the presence of enhanced metabolism revealed signs of the presence
      of NTSR mechanisms to ALS inhibitors in this species. On this basis, selection
      pressure with ALS non-SU inhibitors bears the risk of promoting the evolution of
      NTSR mechanisms in corn poppy.

PMID- 28456306
TI  - Characterization and establishment of a reference deltamethrin and cypermethrin
      resistant tick line (IVRI-IV) of Rhipicephalus (Boophilus) microplus.
AB  - The problem of ticks and tick borne diseases is a global threat and growing
      reports of resistance to commonly used insecticides further aggravated the
      condition and demands for country specific resistance monitoring tools and
      possible solutions of the problem. Establishment of standard reference is
      prerequisite for development of monitoring tools. For studying possible role of
      different mechanisms involved in development of resistance in Rhipicephalus
      (Boophilus) microplus population and to develop newer drug to manage the problem
      of resistance, a deltamethrin exposed and selected tick colony, referred to as
      IVRI-IV, was characterized using reference susceptible IVRI-I tick line as
      control. The RF values of IVRI-IV ticks against deltamethrin, cypermethrin and
      diazinon were determined as 194.0, 26.6, 2.86, respectively, against adults. The
      esterase enzyme ratios of 2.60 and 5.83 was observed using alpha-naphthyl and
      beta-naphthyl acetate while glutathione S-transferase (GST) ratio was 3.77.
      Comparative analysis of IVRI-I and IVRI-IV carboxylesterase gene sequences
      revealed 13 synonymous and 5 non synonymous mutations, reported for the first
      time. The C190A mutation in the domain II S4-5 linker region of sodium channel
      gene leading to leucine to isoleucine (L64I) amino acid substitution was also
      detected in the IVRI-IV population. In the present study, monitorable indicators
      for the maintenance of the reference IVRI-IV colony, the first established
      deltamethrin and cypermethrin resistant tick line of India, were identified.

PMID- 28456307
TI  - RNA interference of Dicer-1 and Argonaute-1 increasing the sensitivity of Aphis
      gossypii Glover (Hemiptera: Aphididae) to plant allelochemical.
AB  - Plant allelochemicals are a group of important defensive agents of plants, which
      have been documented to be deleterious to insect herbivores. In the present
      study, we found that the expression level of Dicer-1 was significantly increased
      when Aphis gossypii adults fed on plant allelochemicals (tannic acid and
      gossypol) incorporated artificial diets. Consider that miRNAs play great
      regulatory roles in various biological processes, this suggested that miRNAs may
      be related to the regulation of enzymes involved in metabolism of plant
      allelochemicals in A. gossypii. To further reveal the roles of miRNAs in the
      response of A. gossypii against plant allelochemicals, both Dicer-1 and Argonaute
      1, an important component of the RNA-induced silencing complex (RISC) in miRNA
      pathway, were silenced using systemic RNA interference (RNAi). The results
      indicated that silence of Dicer-1 reduced the expression of miRNAs, and resulted
      in a high mortality of A. gossypii when fed on both tannic acid and gossypol. The
      silencing of Argonaute-1 resulted in the mortality of A. gossypii by the
      treatment of tannic acid significantly increased compared with control, however,
      the sensitivity of A. gossypii to gossypol was not significantly changed. It
      suggested that miRNAs play potential regulatory roles in the response of A.
      gossypii to plant allelochemicals. These results should be useful to understand
      the molecular mechanisms of the cotton aphid adaption to plant allelochemicals.

PMID- 28456308
TI  - Functional characterization of two acetylcholinesterase genes in the brown citrus
      aphid, Aphis (Toxoptera) citricidus (Kirkaldy), using heterologous expression and
      RNA interference.
AB  - Acetylcholinesterase (AChE) is the primary target of organophosphate- and
      carbamate-based insecticides. We sequenced the full-length cDNAs of two AChE
      genes from the brown citrus aphid Aphis (Toxoptera) citricidus (Kirkaldy). These
      two genes, Tcace1 and Tcace2, which encode TcAChE1 and TcAChE2, respectively, had
      a shared amino acid identity of 29% and were highly similar to other insect ace1
      and ace2 genes, respectively, having specific functional motifs. Potential
      differences in enzymatic function were characterized by the heterologous
      expression of the two genes using a baculovirus system in Sf9 insect cells. Both
      of the recombinant AChEs had high specific activities for three typical
      substrates, acetylthiocholine iodide, butyrylthiocholine iodide, and
      propinylthiocholine iodide. TcAChE1 had a lower Michaelis-Menten constant value
      and a higher maximal reaction velocity than recombinant TcAChE2, indicating a
      higher affinity for substrates and greater catalytic efficiency, respectively.
      Bioassays showed a greater sensitivity of recombinant TcAChE1 to the 10 tested
      insecticides. Silencing of Tcace1 and Tcace2 by RNA interference significantly
      increased the susceptibility of A. citricidus to malathion and carbaryl; however,
      silencing Tcace1 resulted in a higher mortality rate than silencing Tcace2.
      Additionally, the specific enzyme activity decreased more after silencing Tcace1
      than after silencing Tcace2. Thus, TcAChE1 plays a major role in postsynaptic
      neurotransmission in A. citricidus.

PMID- 28456309
TI  - Molecular docking of protease from Metarhizium anisopliae and their toxic effect
      against model insect Galleria mellonella.
AB  - Fungal virulence has been mostly associated with cuticle-degrading enzymes, which
      form the first formidable barrier to pathogens and pass through certain discrete
      stages before breaching the insect cuticle. The present study was conducted to
      extract and purify the extracellular protease enzyme from three isolates from
      Metarhizium anisopliae. The molecular weight of protease enzyme from each isolate
      was identified using sodium dodecyl sulphate-polyacrylamide gel electrophoresis
      (SDS-PAGE) and found to be 35-40kDa. The partially purified enzymes were tested
      to identify its toxic effects against the developmental stages of IVth instar
      larvae of Galleria mellonella and the mortality of larvae among the three
      isolates was observed. The Tk6 isolate showed an ascending effect after 48h of
      exposure, with highest mortality at 120h post inoculation. It also showed more
      virulence against the model insect compared to other strains. Tk6 isolate's
      active protein band was analyzed by MALDI-TOF and docking study was carried out
      to find the interaction between the fungal and insect proteins.

PMID- 28456310
TI  - Deltamethrin affects the expression of voltage-gated calcium channel alpha1
      subunits and the locomotion, egg-laying, foraging behavior of Caenorhabditis
      elegans.
AB  - Deltamethrin belongs to the class of synthetic pyrethroids, which are being
      widely used as insecticides in agricultural practices. Voltage-gated sodium
      channels (VGSCs) are the primary targets of these chemicals for toxicity to
      insects. Caenorhabditis elegans (C. elegans) does not have VGSCs but is
      susceptible to deltamethrin. Recent findings have suggested that pyrethroids can
      affect voltage-gated calcium channels (VGCCs). However, it remains elusive
      whether deltamethrin induces toxicity to C. elegans via modulating the activity
      of VGCCs. To identify the potential target of deltamethrin, we exposed C. elegans
      to different concentrations of deltamethrin and Ca2+ channel blockers for
      different times, characterized the behavioral toxicity of deltamethrin on C.
      elegans, and determined the expression of egl-19, unc-2, and cca-1, which encode
      the alpha1-subunit of the L-, R/N/P/Q-, and T-type VGCC, respectively. We found
      that deltamethrin inhibited the locomotion, egg-laying and foraging ability of C.
      elegans in a concentration dependent manner. We also showed that body length of
      worms on agar plates containing 200mgL-1 deltamethrin for 12h was not
      significantly different from controls, whereas the cholinesterase inhibitor
      carbofuran caused hypercontraction which is a characteristic of organophosphates
      and carbamates, suggesting that deltamethrin's mode of action is distinct from
      those nematicides. In addition, unc-2 was significantly up-regulated following
      0.05mgL-1 deltamethrin exposure for 24h; while egl-19 and cca-1 were
      significantly up-regulated following 5 and 50mgL-1 deltamethrin exposure for 24h.
      Further tests of worms' sensitivity and expression of three alpha1-subunits of
      VGCC to Ca2+ channel blockers indicate that deltamethrin may induce toxic
      behavior C. elegans via modulation of the expression of the alpha1-subunits of
      VGCC. This study provides insights into the linkage between deltamethrin-induced
      toxic behavior and the regulation of alpha1-subunits of VGCC in C. elegans.

PMID- 28456311
TI  - Cross-resistance pattern and basis of resistance in a thiamethoxam-resistant
      strain of Aphis gossypii Glover.
AB  - A thiamethoxam-resistant strain of cotton aphid (ThR) displayed a 13.79-fold
      greater resistance to thiamethoxam than a susceptible cotton aphid (SS) strain.
      Piperonyl butoxide (PBO) and triphenyl phosphate (TPP) synergistically increased
      the toxicity of thiamethoxam in the resistant strain, whereas diethyl maleate
      (DEM) did not exhibit significant synergistic effects. Bioassay results indicated
      that the ThR strain developed increased levels of cross-resistance to bifenthrin
      (11.71 fold), cyfluthrin (17.90 fold), esfenvalerate (6.85 fold), clothianidin
      (6.56 fold), methidathion (5.34 fold) and alpha-cypermethrin (4.53 fold) but did
      not show cross-resistance to malathion, omethoate, acephate, chlorpyrifos,
      methomyl, sulfoxaflor or imidacloprid. PBO and TPP increased bifenthrin toxicity
      in the resistant strain by 2.38 and 4.55 fold, respectively. Quantitative real
      time PCR results indicated that the mRNA expression levels of the alpha1, alpha4
      1, alpha4-2, alpha5 and alpha7 subunits decreased significantly by 3.32, 1.60,
      2.05, 5.41 and 1.48 fold, respectively, in the resistant strain compared with
      those in the susceptible strain. However, significant differences were not
      observed in the expression of the alpha2, alpha3 and beta1 subunits. No target
      site mutations within the alpha1, alpha2 and beta1 subunits of nicotinic
      acetylcholine receptors (nAChRs) were detectable in the ThR strain. In
      conclusion, the levels of thiamethoxam resistance and cross-resistance to other
      insecticides observed in the ThR strain are likely regulated by two mechanisms,
      which include the overexpression of detoxification-related P450s and esterase.
      These results should be useful for the understanding thiamethoxam resistance
      mechanism and the management of insecticide-resistant cotton aphids in China.

PMID- 28456312
TI  - Characterization of boscalid-resistance conferring mutations in the SdhB subunit
      of respiratory complex II and impact on fitness and mycotoxin production in
      Penicillium expansum laboratory strains.
AB  - Laboratory mutants of Penicillium expansum highly resistant (Rfs: 90 to >500,
      based on EC50s) to Succinate Dehydrogenase Inhibitors (SDHIs) were isolated after
      UV-mutagenesis and selection on media containing boscalid. A positive correlation
      was found between sensitivity of isolates to boscalid and other SDHIs such as
      isopyrazam and carboxin but not to fungicides affecting other cellular pathways
      or processes, such as the triazole flusilazole, the phenylpyrrole fludioxonil,
      the anilinopyrimidine cyprodinil and the benzimidazole benomyl. Most of the
      boscalid-resistant strains were more sensitive to the SDHI fluopyram and the QoI
      pyraclostrobin. In order to investigate the mechanism responsible for the
      observed resistance profiles, part of the SdhB subunit isolated the wild type and
      boscalid-resistant isolates, was genetically characterized. Comparison of the
      deduced amino-acid sequence between resistant and wild-type isolates revealed two
      point mutations at a position corresponding to codon 272 of the respective SdhB
      protein in Botrytis cinerea. The substitution of histidine by arginine was found
      in boscalid-resistant isolates which were equally sensitive to fluopyram compared
      with the wild-type whereas the replacement of histidine by tyrosine was found in
      strains with increased sensitivity to fluopyram. No adverse effects of resistance
      mutations were observed on fitness determining parameters such as osmotic
      sensitivity, sporulation and pathogenicity, while mycelial growth rate and spore
      germination was negatively affected in some of the mutants studied. P. expansum
      mutant strains displayed significantly perturbed patulin and citrinin levels as
      compared to the wild-type parent strain both in vitro and in vivo as revealed by
      thin layer (TLC) and high performance liquid chromatography (HPLC).

PMID- 28456314
TI  - Comparison of Frequency of Cardiovascular Events and Mortality in Patients With
      Heart Failure Using Versus Not Using Cocaine.
AB  - Beta-blocker treatment improves left ventricular function, morbidity, and
      survival in patients with systolic heart failure (HF). However, there are limited
      data addressing the safety and efficacy of beta blockers in the setting of
      cocaine use as there is a perceived risk of adverse outcomes. Our aim was to
      determine if beta-blocker treatment was safe in HF patients with a history of
      cocaine use compared with HF patients without history of cocaine use. We also
      examined whether effects differed between cardioselective versus
      noncardioselective beta blockers. Ninety systolic HF patients with cocaine use
      were compared with 177 patients with nonischemic, systolic HF, and no cocaine
      use. Outcomes were HF readmissions, major adverse cardiovascular events, and
      death using multivariable Cox proportional hazard models adjusted for age, black
      race, hypertension, diabetes, coronary artery disease, renal insufficiency, and
      angiotensin-converting enzyme inhibitors. Beta-blocker treatment in systolic HF
      patients with cocaine use did not have significant differences in HF readmissions
      (hazard ratio [HR] 0.66, 95% CI 0.31 to 0.1.38), major adverse cardiovascular
      events (HR 0.58, 95% CI 0.27 to 1.09), death (HR 0.96, 95% CI 0.39 to 2.34), or
      all combined outcomes (HR 0.76, 95% CI 0.39 to 1.47) compared with beta-blocker
      treatment in HF patients without cocaine use. Within HF patients with cocaine
      use, mortality rates (HR 1.50, 95% CI 0.28 to 8.23) were not significantly
      different between patients treated with noncardioselective versus cardioselective
      beta blockers. In conclusion, beta-blocker treatment in systolic HF patients with
      cocaine use was not associated with adverse outcomes.

PMID- 28456315
TI  - Usefulness of the Direct and/or Total Bilirubin to Predict Adverse Outcomes in
      Patients With Acute Decompensated Heart Failure.
AB  - Abnormal liver function test results are often observed in acute decompensated
      heart failure (ADHF). However, the prognostic value of bilirubin fractionation
      has not been elucidated. The prognostic value of direct bilirubin (DB), in
      comparison with total bilirubin (TB), was examined in 556 consecutive patients
      with ADHF. Patients with elevated DB showed mostly similar patient
      characteristics including signs of elevated right-sided pressure (frequent
      hepatomegaly, jugular venous distention, dilated inferior vena cava, and elevated
      gamma-glutamyltransferase) and decreased cardiac output (cold extremities,
      decreased pulse pressure, and lower blood pressure) and other parameters of heart
      failure (HF) severity (increased plasma renin activity, decreased sodium, total
      cholesterol, and ejection fraction) to elevated TB; however, only patients with
      elevated DB showed a significant difference in the frequency of HF history and
      alkaline phosphatase value. Kaplan-Meier analysis showed that patients with
      elevated DB had a significantly higher rate of the composite end point of all
      cause mortality or HF readmission (p = 0.021) compared with those with normal DB,
      whereas patients with elevated TB did not show a statistically significant
      difference compared with those with normal TB (NS). A multivariate Cox hazards
      model showed that DB was an independent predictor of adverse events (adjusted
      hazard ratio 1.052, 95% confidence interval 1.001 to 1.099, p = 0.034), whereas
      TB was not (adjusted hazard ratio 1.017, 95% confidence interval 0.985 to 1.046,
      p = 0.27). Adding DB to existing prognostic variables resulted in higher C
      statistics than adding TB (C-statistics: 0.670 to 0.675, 0.670 to 0.674,
      respectively). In conclusion, elevated DB in ADHF was an independent prognostic
      predictor that was superior to TB. DB may be useful for further risk
      stratification in ADHF.

PMID- 28456316
TI  - Relation of Stress Hormones (Urinary Catecholamines/Cortisol) to Coronary Artery
      Calcium in Men Versus Women (from the Multi-Ethnic Study of Atherosclerosis
      [MESA]).
AB  - The relation between high levels of psychosocial stress and the development of
      coronary artery disease (CAD) has been increasingly recognized, especially in
      women. We hypothesized that simple biomarkers of stress, urinary
      catecholamines/cortisol levels, are associated with more coronary artery calcium
      (CAC), an indicator of CAD, and that this relation is stronger in women compared
      with men. Using data from the Multi-Ethnic Study of Atherosclerosis Stress study,
      we examined the relation between urinary catecholamines/cortisol and CAC. The
      study cohort (n = 654) was 53% women, and 56.4% of the cohort had detectable CAC.
      Multivariable regression analyses assessed the relation between urinary
      catecholamines/cortisol and CAC (odds CAC >0 through logistic and ln CAC through
      Tobit model). There was an association between increased cortisol and increased
      CAC and an inverse association between dopamine and CAC. These relations were
      seen in men and women, with no difference between the genders. In conclusion,
      higher cortisol and lower dopamine levels are independently associated with
      higher CAC to a similar degree in men and women. These simple urinary biomarkers
      contribute to our understanding of the role of stress in the pathogenesis of CAD
      and may be incorporated into future strategies to prevent and treat CAD.

PMID- 28456318
TI  - New tools for APIC members.

PMID- 28456317
TI  - Long-Term Prognostic Value of Appropriate Myocardial Perfusion Imaging.
AB  - Appropriate use criteria (AUC) for single-photon emission computed tomography
      myocardial perfusion images (SPECT-MPIs) were developed to address the growth of
      cardiac imaging studies. Long-term prognostic value of AUC in SPECT-MPI has not
      been tested in existing cohorts. We sought to determine the long-term prognostic
      value of MPI classified as appropriate. AUC was evaluated in a prospectively
      designed cohort of patients who underwent clinically indicated MPI. MPI studies
      were classified based on 2009 AUC for SPECT-MPI. Data regarding downstream
      coronary angiography (cath), revascularization and all-cause mortality, cardiac
      death, and nonfatal myocardial infarction (MI) were collected from national
      registries. Among n = 1,129 MPI scans that received an appropriate grading, 148
      all-cause deaths, 109 MIs, 58 cardiac deaths, 152 caths, 113 revascularization
      procedures occurred over a mean follow-up period of 5.4 +/- 1.2 years (0.9%
      cardiac death rate per year, 1.8% MI rate per year). Most of the scans were low
      risk normal MPI scans (summed stress score <=3; 74.1%). An abnormal scan was
      associated with higher rates of MI (19.5% vs 6.2%, hazard ratio 1.72, p = 0.017)
      and cardiac death (13.4% vs 2.3%, hazard ratio 2.12, p = 0.016). In conclusion,
      MPI scans classified as appropriate have long-term prognostic value, despite a
      high proportion of low-risk scans. This provides support for clinicians to
      consider the use of appropriate grading in addition to MPI scan results in
      patient management.

PMID- 28456319
TI  - Hand hygiene electronic monitoring: Are we there yet?

PMID- 28456320
TI  - Implementing clinical guidelines to prevent catheter-associated urinary tract
      infections and improve catheter care in nursing homes: Systematic review.
AB  - BACKGROUND: Catheter-associated urinary tract infection is the most common health
      care-associated infection, is considered avoidable, and has cost implications for
      health services. Prevalence is high in nursing homes, but little research has
      been undertaken to establish whether implementing clinical guidelines can reduce
      infection rates in long-term care or improve quality of urinary catheter care.
      METHODS: Systematic search and critical appraisal of the literature. RESULTS:
      Three studies evaluated the impact of implementing a complete clinical guideline.
      Five additional studies evaluated the impact of implementing individual elements
      of a clinical guideline. CONCLUSIONS: Prevention of catheter-associated urinary
      tract infection in nursing homes has received little clinical or research
      attention. Studies concerned with whole guideline implementation emerged as
      methodologically poor using recognized criteria for critically appraising
      epidemiologic studies concerned with infection prevention. Research evaluating
      the impact of single elements of clinical guidelines is more robust, and their
      findings could be implemented to prevent urinary infections in nursing homes.

PMID- 28456321
TI  - Prevalence of multidrug-resistant gram-negative bacteria among nursing home
      residents: A systematic review and meta-analysis.
AB  - BACKGROUND: Multidrug-resistant gram-negative bacteria (MDR-GNB) are associated
      with an increasing proportion of infections among nursing home (NH) residents.
      The objective of this systematic review and meta-analysis was to critically
      review evidence of the prevalence of MDR-GNB among NH residents. METHODS:
      Following Meta-Analysis of Observational Studies in Epidemiology guidelines, a
      systematic review of literature for the years 2005-2016 using multiple databases
      was conducted. Study quality, appraised by 2 reviewers, used Downs and Black risk
      of bias criteria. Studies reporting prevalence of MDR-GNB colonization were
      pooled using a random effects meta-analysis model. Heterogeneity was assessed
      using Cochran Q and I2 statistics. RESULTS: Of 327 articles, 12 met the criteria
      for review; of these, 8 met the criteria for meta-analysis. Escherichia coli
      accounted for the largest proportion of isolates. Reported MDR-GNB colonization
      prevalence ranged from 11.2%-59.1%. Pooled prevalence for MDR-GNB colonization,
      representing data from 2,720 NH residents, was 27% (95% confidence interval,
      15.2%-44.1%) with heterogeneity (Q = 405.6; P = .01; I2 = 98.3). Two studies
      reported MDR-GNB infection rates of 10.9% and 62.7%. CONCLUSION: Our findings
      suggest a high prevalence of MDR-GNB colonization among NH residents, emphasizing
      the need to enhance policies for infection control and prevention (ICP) in NHs.

PMID- 28456322
TI  - Electronic monitoring in combination with direct observation as a means to
      significantly improve hand hygiene compliance.
AB  - Monitoring hand hygiene compliance among health care personnel (HCP) is an
      essential element of hand hygiene promotion programs. Observation by trained
      auditors is considered the gold standard method for establishing hand hygiene
      compliance rates. Advantages of observational surveys include the unique ability
      to establish compliance with all of the World Health Organization "My 5 Moments
      for Hand Hygiene" initiative Moments and to provide just-in-time coaching.
      Disadvantages include the resources required for observational surveys,
      insufficient sample sizes, and nonstandardized methods of conducting
      observations. Electronic and camera-based systems can monitor hand hygiene
      performance on all work shifts without a Hawthorne effect and provide
      significantly more data regarding hand hygiene performance. Disadvantages include
      the cost of installation, variable accuracy in estimating compliance rates,
      issues related to acceptance by HCP, insufficient data regarding their cost
      effectiveness and influence on health care-related infection rates, and the
      ability of most systems to monitor only surrogates for Moments 1, 4, and 5.
      Increasing evidence suggests that monitoring only Moments 1, 4, and 5 provides
      reasonable estimates of compliance with all 5 Moments. With continued improvement
      of electronic monitoring systems, combining electronic monitoring with
      observational methods may provide the best information as part of a multimodal
      strategy to improve and sustain hand hygiene compliance rates among HCP.

PMID- 28456323
TI  - Developing a user-friendly report for electronically assisted surveillance of
      catheter-associated urinary tract infection.
AB  - Catheter-associated urinary tract infection (CAUTI) surveillance is labor
      intensive, generally involving manual medical record review. We developed a
      prototype automated report through iterative design. Surveys and qualitative
      interviews were administered to key stakeholders to assess the report design. We
      found that different provider types expressed different needs regarding report
      content and format. Therefore, determining the primary audience for reporting
      data on CAUTI a priori is critical to developing useful reports, particularly as
      this process becomes standardized and automated.

PMID- 28456324
TI  - Reply.

PMID- 28456325
TI  - Extending the parameter range for tDCS: Safety and tolerability of 4 mA
      stimulation.

PMID- 28456326
TI  - Withdrawal notice: Long-term follow-up after abdominal cerclage: A population
      based cohort study.

PMID- 28456328
TI  - Editorial overview: Beyond native biocatalysts and natural biotransformations.

PMID- 28456327
TI  - Impact of Vitiligo on Quality of Life.
AB  - INTRODUCTION AND OBJECTIVE: Vitiligo is a chronic autoimmune skin disease caused
      by the destruction of melanocytes. Although quality of life (QOL) in vitiligo has
      been studied in different countries, it has not yet been investigated in Mexico.
      The aim of this study was to assess the QOL of Mexican patients with vitiligo.
      MATERIAL AND METHOD: We conducted a cross-sectional study at the research unit of
      Centro Dermatologico Dr. Ladislao de la Pascua in Mexico City. We included adults
      with vitiligo and excluded those with other pigmentation disorders or a
      neurological or psychiatric disorder. Patients on psychoactive medications were
      also excluded. All the patients were administered the Dermatology Life Quality
      Index (DLQI), a vitiligo-specific quality of life instrument (the VitiQoL), and
      the Beck Depression and Anxiety Inventories. RESULTS: We studied 150 patients
      with vitiligo (103 women [68.7%] and 47 men [31.3%]). The median (interquartile
      range) age was 38 (20) years. The mean (SD) scores on the DLQI and VitiQoL were
      5.2 (5.4) and 32.1 (22.7) out of total possible scores of 30 and 90,
      respectively. The correlation between questionnaire scores was 0.675 (P<.001).
      Patients with genital involvement scored significantly worse on the VitiQoL than
      those without lesions in this area (43.95 [28.4]) vs. 28.98 [20.08], P<.001). The
      prevalence of depression and anxiety was 34% and 60%, respectively. CONCLUSION:
      Vitiligo has a minimal impact on the QOL of our patients. QOL was worse in
      patients with genital lesions.

PMID- 28456329
TI  - Editorial overview: Nine short stories of metals in biology.

PMID- 28456330
TI  - The Effects of beta-Adrenergic Blockade on the Degrading Effects of Eye Movements
      on Negative Autobiographical Memories.
AB  - BACKGROUND: Eye movement desensitization and reprocessing (EMDR) is an effective
      treatment for posttraumatic stress disorder. During EMDR, patients make
      horizontal eye movements (EMs) while simultaneously recalling a traumatic memory,
      which renders the memory less vivid and emotional when it is later recalled
      again. Recalling highly emotional autobiographical memories enhances
      noradrenergic neurotransmission. Noradrenaline (NA) strengthens memory
      (re)consolidation. However, memories become less vivid after recall+EMs.
      Therefore, NA might either play no significant role or serve to strengthen
      memories that are degraded by EMs. The present study was designed to test the
      latter hypothesis. We predicted that blocking NA would abolish the memory
      degrading effects of EMs. METHODS: Fifty-six healthy participants selected three
      negative autobiographical memories. One was then recalled while making EMs, one
      was recalled without EMs, and one was not recalled. Vividness and emotionality of
      the memories as well as heart rate and skin conductance level during memory
      retrieval were measured before, directly after, and 24 hours after the EM task.
      Before the task, participants received a placebo or the noradrenergic beta
      receptor blocker propranolol (40 mg). RESULTS: There were no effects of EMs on
      memory emotionality or psychophysiological measures in the propranolol and
      placebo groups. However, in the placebo group, but not in the propranolol group,
      memory vividness significantly decreased from pretest to posttest and follow-up
      after recall+EMs relative to the control conditions. CONCLUSIONS: Blocking NA
      abolished the effects of EMs on the vividness of emotional memories, indicating
      that NA is crucial for EMDR effectiveness and possibly strengthens the
      reconsolidation of the degraded memory.

PMID- 28456331
TI  - Complexin Binding to Membranes and Acceptor t-SNAREs Explains Its Clamping Effect
      on Fusion.
AB  - Complexin-1 is a SNARE effector protein that decreases spontaneous
      neurotransmitter release and enhances evoked release. Complexin binds to the
      fully assembled four-helical neuronal SNARE core complex as revealed in competing
      molecular models derived from x-ray crystallography. Presently, it is unclear how
      complexin binding to the postfusion complex accounts for its effects upon
      spontaneous and evoked release in vivo. Using a combination of spectroscopic and
      imaging methods, we characterize in molecular detail how complexin binds to the
      1:1 plasma membrane t-SNARE complex of syntaxin-1a and SNAP-25 while
      simultaneously binding the lipid bilayer at both its N- and C-terminal ends.
      These interactions are cooperative, and binding to the prefusion acceptor t-SNARE
      complex is stronger than to the postfusion core complex. This complexin
      interaction reduces the affinity of synaptobrevin-2 for the 1:1 complex, thereby
      retarding SNARE assembly and vesicle docking in vitro. The results provide the
      basis for molecular models that account for the observed clamping effect of
      complexin beginning with the acceptor t-SNARE complex and the subsequent
      activation of the clamped complex by Ca2+ and synaptotagmin.

PMID- 28456332
TI  - CAT & MAUS: A novel system for true dynamic motion measurement of underlying bony
      structures with compensation for soft tissue movement.
AB  - Optoelectronic motion capture systems are widely employed to measure the movement
      of human joints. However, there can be a significant discrepancy between the data
      obtained by a motion capture system (MCS) and the actual movement of underlying
      bony structures, which is attributed to soft tissue artefact. In this paper, a
      computer-aided tracking and motion analysis with ultrasound (CAT & MAUS) system
      with an augmented globally optimal registration algorithm is presented to
      dynamically track the underlying bony structure during movement. The augmented
      registration part of CAT & MAUS was validated with a high system accuracy of 80%.
      The Euclidean distance between the marker-based bony landmark and the bony
      landmark tracked by CAT & MAUS was calculated to quantify the measurement error
      of an MCS caused by soft tissue artefact during movement. The average Euclidean
      distance between the target bony landmark measured by each of the CAT & MAUS
      system and the MCS alone varied from 8.32mm to 16.87mm in gait. This indicates
      the discrepancy between the MCS measured bony landmark and the actual underlying
      bony landmark. Moreover, Procrustes analysis was applied to demonstrate that CAT
      & MAUS reduces the deformation of the body segment shape modeled by markers
      during motion. The augmented CAT & MAUS system shows its potential to dynamically
      detect and locate actual underlying bony landmarks, which reduces the MCS
      measurement error caused by soft tissue artefact during movement.

PMID- 28456333
TI  - How symmetric are metal-on-metal hip resurfacing patients during gait? Insights
      for the rehabilitation.
AB  - Metal-on-metal hip resurfacing patients demonstrate hip biomechanics closer to
      normal in comparison to total hip arthroplasty during gait. However, it is not
      clear how symmetric is the gait of hip resurfacing patients. Biomechanical data
      of 12 unilateral metal-on-metal hip resurfacing participants were collected
      during gait at a mean time of 45months (SD 24) after surgery. Ankle, knee, hip,
      pelvis and trunk kinematics and kinetics of both sides were measured with a
      motion and force-capture system. Principal component analysis and mean
      hypothesis' tests were used to compare the operated and healthy sides. The
      operated side had prolonged ankle eversion angle during late stance and delayed
      increased ankle inversion angle during early swing (p=0.008; effect size=0.70),
      increased ankle inversion moment during late stance (p=0.001; effect size=0.78),
      increased knee adduction angle during swing (p=0.044; effect size=0.57),
      decreased knee abduction moment during stance (p=0.05; effect size=0.40),
      decreased hip range of motion in the sagittal plane (p=0.046; effect size=0.56),
      decreased range of hip abduction moment during stance (p=0.02; effect size=0.63),
      increased hip range of motion in the transverse plane (p=0.02; effect size=0.62),
      decreased hip internal rotation moment during the transition from loading
      response to midstance (p=0.001; effect size=0.81) and increased trunk ipsilateral
      lean (p=0.03; effect size=0.60). Therefore, hip resurfacing patients have some
      degree of asymmetry in long term, which may be related to hip weakness and
      decreased range of motion, to foot misalignments and to strategies implemented to
      reduce loading on the operated hip. Interventions such as muscle strengthening
      and stretching, insoles and gait feedback training may help improving symmetry
      following hip resurfacing.

PMID- 28456334
TI  - Isoperistaltic versus antiperistaltic stapled side-to-side anastomosis for colon
      cancer surgery.

PMID- 28456335
TI  - Acute lymphoblastic leukemia in adults: Steps ahead.

PMID- 28456336
TI  - A Full-Capacity Protocol Allows for Increased Emergency Patient Volume and
      Hospital Admissions.
AB  - PROBLEM: Our hospital was encountering problems with ED crowding. We sought to
      determine the impact of implementing a full-capacity protocol to respond to
      anticipated or actual crowding conditions. Our full-capacity protocol is based on
      collaboration among multiple hospital units. METHODS: We completed a quality
      improvement initiative using a pre/post analysis of all ED patient encounters
      after implementing a full-capacity protocol with a corresponding period from the
      prior year. The principal outcomes measured were patient volume, admission rate,
      patient left without being seen (LWBS) rate, length of stay, and ambulance
      diversion hours. RESULTS: In the post-full-capacity protocol period, a 7.4%
      increase in emergency patient encounters (P < .001) and an 11.9% increase in
      admissions (P < .001) were noted compared with the corresponding period in 2013.
      Also noted in the study period were a 10.2% decrease in LWBS rate (P = .29), an
      increase in length of stay of 34 minutes (P < .001), and a 92% decrease in
      ambulance diversion hours (111 fewer hours, P < .001). IMPLICATIONS FOR PRACTICE:
      The collaborative full-capacity protocol was effective in reducing LWBS and
      ambulance diversion, while accommodating a significant increase in ED volume and
      increased hospital admission rates at our institution.

PMID- 28456337
TI  - Corrigendum to "Plasma metabolomics in adults with cystic fibrosis during a
      pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3
      administration" [Metabolism vol. 70, May 2017, pages 31-41].

PMID- 28456338
TI  - Urgent care medicine and the role of the APP within this specialty.
AB  - The field of urgent care medicine offers an additional medical pathway for
      patients who have immediate, but non-life-threatening, medical concerns. Urgent
      care medicine offers a more varied set of resources and services than a physician
      office setting, with more flexible hours. This gives patients an opportunity to
      not have to go to the emergency department for non-emergent care. As a newer
      specialty within the medical field, certain roles of healthcare providers other
      than physicians are becoming established, including the advanced practice
      provider (APP). An APP is a nurse practitioner or a physician assistant, who is
      licensed to treat under the supervision of a physician. Nurse practitioners' (NP)
      and physician assistants' (PA) role in urgent care is often seen as an effective,
      lower cost option to manage common acute minor illnesses seen in the community.
      Benefits to utilizing APPs in urgent care include decreasing costs to both the
      patient and health system, enhancing the physician's ability to see more
      patients, and decreasing wait times, all while continuing to maintain high
      standards of care. The goal of the authors within this publication is to discuss
      urgent care as a specialty and further explore the role of advanced practice
      providers within this setting.

PMID- 28456339
TI  - The minimum basic dataset for diagnoses of cerebrovascular disease:
      Methodological issue on reliability.
AB  - Reliability (precision, repeatability, agreement) and validity (accuracy) are two
      completely different issues which should be assessed using appropriate tests. It
      is crucial to know that, reporting concordance rate; the selection error rate and
      the classification error rate are not the most appropriate estimates to assess
      reliability. Regarding reliability, for qualitative variables, weighted kappa
      should be used with caution. However, sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), likelihood ratio
      positive and negative as well as diagnostic accuracy are estimates that are
      usually used to evaluate the validity of a test compared to a gold standard.

PMID- 28456340
TI  - Transient neocortical MRI abnormalities following initial epileptic seizure.

PMID- 28456341
TI  - Patient-centered surgical prehabilitation.

PMID- 28456342
TI  - Comparison of inflammatory cytokines in peritoneal fluid at source control
      surgery for abdominal sepsis.
AB  - BACKGROUND: Open abdomen with vacuum assisted closure (VAC) is an alternate
      method to primary abdominal closure (PAC) in select situations for the management
      of severe surgical abdominal sepsis or septic shock. Peritoneal cytokines may
      potentially correlate with deranged physiology and help stratify severity of
      sepsis. The primary objective of the study was to identify if cytokines can
      differentiate between patients who underwent PAC or VAC at primary source control
      laparotomy (SCL). METHODS: Prospective case series including patients with severe
      abdominal sepsis/septic shock requiring urgent SCL. Peritoneal fluid (PF) was
      collected intra-operatively and blood samples were collected pre- and post SCL.
      Samples were analyzed with a Cytokine 30-plex Panel. APACHE-IV was used as a
      measure of disease severity between groups. RESULTS: 4 PAC and 8 VAC patients
      were included. PF concentrations of IL 6, IL-17, IL-5 and HGF were significantly
      elevated in VAC compared to PAC. Serum RANTES was increased in survivors compared
      to non-survivors. CONCLUSIONS: Patients who received VAC management had a more
      severe degree of local abdominal sepsis based on significantly elevated
      peritoneal cytokines.

PMID- 28456343
TI  - Reconsidering Drone Warfare.

PMID- 28456344
TI  - Multiplexed Point-of-Care Testing - xPOCT.
AB  - Multiplexed point-of-care testing (xPOCT), which is simultaneous on-site
      detection of different analytes from a single specimen, has recently gained
      increasing importance for clinical diagnostics, with emerging applications in
      resource-limited settings (such as in the developing world, in doctors' offices,
      or directly at home). Nevertheless, only single-analyte approaches are typically
      considered as the major paradigm in many reviews of point-of-care testing. Here,
      we comprehensively review the present diagnostic systems and techniques for xPOCT
      applications. Different multiplexing technologies (e.g., bead- or array-based
      systems) are considered along with their detection methods (e.g., electrochemical
      or optical). We also address the unmet needs and challenges of xPOCT. Finally, we
      critically summarize the in-field applicability and the future perspectives of
      the presented approaches.

PMID- 28456345
TI  - Urinary Anomalies in 22q11.2 Deletion (DiGeorge syndrome): From Copy Number
      Variations to Single-Gene Determinants of Phenotype.

PMID- 28456347
TI  - The Effects of Feedback on Adherence to Treatment: A Systematic Review and Meta
      analysis of RCTs.
AB  - CONTEXT: The aim of this systematic review is to determine whether providing
      feedback, guided by subjective or objective measures of adherence, improves
      adherence to treatment. EVIDENCE ACQUISITION: Data sources included MEDLINE,
      Embase, CINAHL, and PsycINFO, and reference lists of retrieved articles. Only
      RCTs comparing the effect of feedback on adherence outcome were included. Three
      independent reviewers extracted data for all potentially eligible studies using
      an adaptation of the Cochrane Library data extraction sheet. The primary outcome,
      change in adherence, was obtained by measuring the difference between adherence
      at baseline visit (prior to feedback) and at the last visit (post-feedback).
      EVIDENCE SYNTHESIS: Twenty-four studies were included in the systematic review,
      and 16 found a significant improvement in adherence in the intervention group
      (change in adherence range, -13% to +22%), whereas adherence worsened in the
      control group (change in adherence range, -32% to 10.2%). Meta-analysis included
      six studies, and the pooled effect showed that mean percentage adherence
      increased by 10.02% (95% CI=3.15%, 16.89%, p=0.004) more between baseline and
      follow-up in the intervention groups compared with control groups. Meta
      regression confirmed that study quality, form of monitoring adherence, delivery
      of feedback, or study duration did not influence effect size. CONCLUSIONS:
      Feedback guided by objective or subjective measures of adherence improves
      adherence and, perhaps more importantly, prevents worsening of adherence over
      time even when only small absolute improvements in adherence were noted.
      Increased use of feedback to improve treatment adherence has the potential to
      reduce avoidable healthcare costs caused by non-adherence.

PMID- 28456348
TI  - The Decipher Genomic Classifier Independently Improves Prognostication for
      Patients After Prostatectomy.

PMID- 28456346
TI  - Management of Gout and Hyperuricemia in CKD.
AB  - Hyperuricemia and gout, the clinical manifestation of monosodium urate crystal
      deposition, are common in patients with chronic kidney disease (CKD). Although
      the presence of CKD poses additional challenges in gout management, effective
      urate lowering is possible for most patients with CKD. Initial doses of urate
      lowering therapy are lower than in the non-CKD population, whereas incremental
      dose escalation is guided by regular monitoring of serum urate levels to reach
      the target level of <6mg/dL (or <5mg/dL for patients with tophi). Management of
      gout flares with presently available agents can be more challenging due to
      potential nephrotoxicity and/or contraindications in the setting of other common
      comorbid conditions. At present, asymptomatic hyperuricemia is not an indication
      for urate-lowering therapy, though emerging data may support a potential
      renoprotective effect.

PMID- 28456349
TI  - Towards a Greater Understanding of Underactive Bladder.

PMID- 28456350
TI  - What are the Benefits and Harms of Ureteroscopy Compared with Shock-wave
      Lithotripsy in the Treatment of Upper Ureteral Stones? A Systematic Review.
AB  - CONTEXT: Extracorporeal shock wave lithotripsy (SWL) and ureteroscopy (URS), with
      or without intracorporeal lithotripsy, are the most common treatments for upper
      ureteric stones. With advances in technology, it is unclear which treatment is
      most effective and/or safest. OBJECTIVE: To systematically review literature
      reporting benefits and harms of SWL and URS in the management of upper ureteric
      stones. EVIDENCE ACQUISITION: Databases including Medline, Embase, and the
      Cochrane library were searched from January 2000 to November 2014. All randomised
      controlled trials (RCTs), quasi-randomised controlled trials, and nonrandomised
      studies comparing any subtype or variation of URS and SWL were included. The
      primary benefit outcome was stone-free rate (SFR). The primary harm outcome was
      complications. Secondary outcomes included retreatment rate, need for secondary,
      and/or adjunctive procedures. The Cochrane risk of bias tool was used to assess
      RCTs, and an extended version was used to assess nonrandomised studies. Grading
      of Recommendations Assessment, Development, and Evaluation was used to assess the
      quality of evidence. EVIDENCE SYNTHESIS: Five thousand-three hundred and eighty
      abstracts and 387 full-text articles were screened. Forty-seven studies met
      inclusion criteria; 19 (39.6%) were RCTs. No studies on children met inclusion
      criteria. URS and SWL were compared in 22 studies (4 RCTs, 1 quasi-randomised
      controlled trial, and 17 nonrandomised studies). Meta-analyses were inappropriate
      due to data heterogeneity. SFR favoured URS in 9/22 studies. Retreatment rates
      were higher for SWL compared with URS in all studies but one. Longer hospital
      stay and adjunctive procedures (most commonly the insertion of a JJ stent) were
      more common when primary treatment was URS. Complications were reported in 11 out
      of 22 studies. In eight studies, it was possible to report this as a Clavien
      Dindo Grade. Higher complication rates across all grades were reported for URS
      compared with SWL. For intragroup (intra-SWL and intra-URS) comparative studies,
      25 met the inclusion criteria. These studies varied greatly in outcomes measured
      with data being heterogeneous. CONCLUSIONS: Compared with SWL, URS was associated
      with a significantly greater SFR up to 4 wk but the difference was not
      significant at 3 mo in the included studies. URS was associated with fewer
      retreatments and need for secondary procedures, but with a higher need for
      adjunctive procedures, greater complication rates, and longer hospital stay.
      PATIENT SUMMARY: In this paper, the relative benefits and harms of the two most
      commonly offered treatment options for urinary stones located in the upper ureter
      were reviewed. We found that both treatments are safe and effective options that
      should be offered based on individual patient circumstances and preferences.

PMID- 28456351
TI  - Synthesis of novel chlorhexidine spheres with controlled release from a UDMA-HEMA
      resin using ultrasound.
AB  - OBJECTIVE: Establish the release kinetics of new chlorhexidine particles
      incorporated in a dental resin, and with the application of ultrasound. METHODS:
      Spherical chlorhexidine particles (SCP) were synthesized (5wt%), freeze dried and
      incorporated into UDMA-HEMA resins. Chlorhexidine diacetate (CDP) (5wt%) was
      similarly incorporated in separate resins. Resin discs were immersed in deionized
      water, and a release profile established (650h). Ultrasound was used to trigger
      chlorhexidine (CHX) release from the resin discs at specific durations (10-30s)
      and time intervals (1-425h). Chlorhexidine content was determined by UV-vis
      absorption. The chlorhexidine particles/polymer composites were characterized
      using TGA, SEM, and confocal microscopy. RESULTS: SCP exhibited structures with
      high chlorhexidine content (90-95%), and a Mean (SD) diameter of 17.2 (2.5)MUm
      which was significantly (p<0.001) smaller than the CDP crystals at 53.6
      (33.7)MUm. The SCP discs had a lower (7.7%) CHX release compared to the CDP group
      (16.2%). Ultrasonication of the resin discs with increasing durations (10-30s)
      resulted in higher drug release rates. CDP release rates (CHX) over 650h were:
      23.5% (10s), 42.6% (20s), 51.2% (30s), and for SCP (CHX) were; 9.8% (10s), 12.3%
      (20s), and 14.0% (30s). SEM/confocal microscopy revealed CDP discs exhibited
      dissolution associated with the particle surface and SCP from the interior.
      SIGNIFICANCE: Chlorhexidine spheres incorporated in a dental resin demonstrated a
      responsive and lower CHX release. Ultrasound enhanced CHX release and is useful
      in clinical situations where the drug is required on demand to treat severe or
      persistent infections.

PMID- 28456352
TI  - Bow-hunter's syndrome due to left C7 schwannoma in a patient with bilateral
      absence of the posterior inferior cerebellar artery.

PMID- 28456353
TI  - A prospective study of recovery from leg numbness following decompression surgery
      for lumbar spinal stenosis.
AB  - BACKGROUND: Residual leg numbness (LN) following lumbar surgery can lower patient
      satisfaction; however, prospective studies are sparse. The purpose of this study
      was to evaluate recovery from LN following decompression surgery for lumbar
      spinal stenosis (LSS). METHODS: A total of 145 patients with LSS were enrolled.
      All patients underwent decompressive surgery, with or without spinal fusion,
      followed by a 12 month prospective follow-up. The degree of LN and leg pain (LP)
      was assessed using the visual analog scale (VAS), a patient-reported outcome
      measure. RESULTS: Six patients dropped out, and we evaluated 139 patients
      (average age, 68.1 years). The average VAS-LN scores were 5.9 +/- 2.6, 1.8 +/-
      2.3, 2.0 +/- 2.5, 2.1 +/- 2.6, 2.2 +/- 2.5, and 2.1 +/- 2.6, and the average VAS
      LP scores were 5.7 +/- 2.8, 1.2 +/- 1.7, 0.9 +/- 1.5, 1.4 +/- 2.0, 1.4 +/- 2.0,
      and 1.4 +/- 1.9 preoperatively and at 2 weeks, 3, 6, 9, 12 months following the
      surgery, respectively. Significant improvement in VAS-LN and VAS-LP scores was
      observed during the first 2 weeks after the surgery. At 12 months after the
      surgery, the VAS-LN score was significantly greater than the VAS-LP score. The
      change in the VAS-LN score between the preoperative and 12 month-postoperative
      values was significantly smaller than that in the VAS-LP score. Multivariate
      logistic analyses revealed that preoperative symptom duration and preoperative
      dural sac cross-sectional area (DCSA) were the significant independent predictive
      factors for residual LN. CONCLUSIONS: Following lumbar decompression surgery, LN
      improved significantly during the first 2 weeks after surgery. However, the
      improvement in the VAS-LN score was less than in the VAS-LP score. Patients with
      longer preoperative symptom duration and narrow preoperative DCSA showed less LN
      improvement. LEVEL OF EVIDENCE: Level 3.

PMID- 28456354
TI  - Genetic association studies in cardiovascular diseases: Do we have enough power?
AB  - Genetic association studies have a long history of delivering insightful results
      for cardiovascular disease (CVD) research. Beginning with early candidate gene
      studies, to genome-wide association studies, and now on to newer whole-genome
      sequencing studies, research in human genetics has enriched our understanding of
      the pathobiology of CVD. As these studies continue to expand, the issue of
      statistical power plays an important role in study design as well as the
      interpretation of results. We provide an overview of the component parts that
      determine statistical power and preview the future of CVD genetic association
      studies through this lens.

PMID- 28456355
TI  - Potential Mechanisms of Vascular Thrombosis after Microwave Ablation in an in
      Vivo Liver.
AB  - PURPOSE: To evaluate potential biologic and thermal mechanisms of the observed
      differences in thrombosis rates between hepatic vessels during microwave (MW)
      ablation procedures. MATERIALS AND METHODS: MW ablation antennae were placed in
      single liver lobes of 2 in vivo porcine liver models (n = 3 in each animal; N = 6
      total) in the proximity of a large (> 5 mm) portal vein (PV) and hepatic veins
      (HVs). Each ablation was performed with 100 W for 5 minutes. Conventional
      ultrasound imaging and intravascular temperature probes were used to evaluate
      vessel patency and temperature changes during the ablation procedure. Vascular
      endothelium was harvested 1 hour after ablation and used to characterize genes
      and proteins associated with thrombosis in PVs and HVs. RESULTS: Targeted PVs
      within the MW ablation zone exhibited thrombosis at a significantly higher rate
      than HVs (54.5% vs 0.0%; P = .0046). There was a negligible change in
      intravascular temperature in PVs and HVs during the ablation procedure (0.2
      degrees C +/- 0.4 vs 0.6 degrees C +/- 0.9; P = .46). PVs exhibited significantly
      higher gene expression than HVs in terms of fold differences in thrombomodulin
      (2.9 +/- 2.0; P = .0001), von Willebrand factor (vWF; 7.6 +/- 1.5; P = .0001),
      endothelial protein C receptor (3.50 +/- 0.49; P = .0011), and plasminogen
      activator inhibitor (1.46 +/- 0.05; P = .0014). Western blot analysis showed
      significantly higher expression of vWF (2.32 +/- 0.92; P = .031) in PVs compared
      with HVs. CONCLUSIONS: Large PVs exhibit thrombosis more frequently than HVs
      during MW ablation procedures. Biologic differences in thrombogenicity, rather
      than heat transfer, between PVs and HVs may contribute to their different rates
      of thrombosis.

PMID- 28456357
TI  - The value of direct observation to reduce catheter-associated urinary tract
      infection.

PMID- 28456356
TI  - The relationship between right ventricular deformation and heart rate variability
      in asymptomatic diabetic patients.
AB  - OBJECTIVE: To investigate heart rate variability (HRV) and right ventricular (RV)
      remodeling in asymptomatic diabetic patients, as well as the relationship between
      HRV indices and RV structure, function and deformation. METHOD: This cross
      sectional study included 59 asymptomatic patients with type 2 diabetes and 45
      healthy controls without cardiovascular risk factors. All study subjects
      underwent 24-h Holter monitoring, laboratory analyses and complete two
      dimensional echocardiography examination (2DE). RESULTS: RV diastolic function
      and longitudinal deformation were significantly impaired in diabetic individuals
      comparing with controls. RV global longitudinal strain and layer-specific
      longitudinal strains were significantly decreased in diabetic group. The same
      trend of changes in RV deformation was observed for global RV and lateral wall.
      All parameters of time and frequency domain of HRV were reduced in diabetic
      subjects. RV endocardial longitudinal strain together with LV mass index, mitral
      E/e' ratio and HbA1c correlated with HRV parameters. However, multivariate linear
      regression analysis showed that only RV endocardial longitudinal strain and LV
      mass index are associated with HRV parameters independently of age, BMI, HbA1c,
      RV free wall thickness and pulmonary artery pressure. CONCLUSIONS: RV
      subendocardial strain is independently associated with HRV parameters in the
      whole study population. This reveals potentially important role of determination
      of layer-specific RV longitudinal function as important marker of preclinical
      cardiac damage, but also indirectly show the impairment of cardiac autonomic
      function in diabetic patients.

PMID- 28456358
TI  - Patient Outcomes as a Function of Shoulder Surgeon Volume: A Systematic Review.
AB  - PURPOSE: To examine surgical complications, length of stay, surgical time, cost,
      revision rates, clinical outcomes, current surgical trends. and minimum number of
      cases in relationship to surgeon volume for shoulder arthroplasty and rotator
      cuff repair. METHODS: We performed a systematic review of studies using the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
      All studies that met inclusion criteria from January 1990 to January 2016 were
      included. Inclusion criteria included Level IV evidence or greater, contained
      specific surgeon volume, and were written in or translated into English.
      Exclusion criteria included non-English manuscripts, abstracts, and review
      papers. A written protocol was used to extract relevant data and evaluate study
      results. Data extracted included volume-specific data pertaining to length of
      stay, operating time, complications, and cost. RESULTS: A total of 10 studies
      were included. Seven studies evaluated arthroplasty with 88,740 shoulders, and 3
      studies evaluated rotator cuff repair with 63,535 shoulders. Variation was seen
      in how studies defined low- versus high-volume surgeon. For arthroplasty, <5
      cases per year met the criteria for a low-volume surgeon and were associated with
      increased length of stay, longer operating room time, increased in-hospital
      complications, and increased cost. Mortality was not significantly increased. In
      rotator cuff surgery, <12 surgeries per year met the criteria for low volume and
      were associated with increased length of stay, increased operating room time, and
      increase in reoperation rate. CONCLUSIONS: Our systematic review demonstrates
      increased surgical complications, length of stay, surgical time, and surgical
      cost in shoulder arthroplasty and rotator cuff repair when performed by a low
      volume shoulder surgeon, which is defined by those performing <5 arthroplasties
      and/or <12 rotator cuff repairs per year. LEVEL OF EVIDENCE: Level III,
      systematic review of Level II and III studies.

PMID- 28456359
TI  - The use of countercurrent chromatography in the separation of nonpolar lipid
      compounds.
AB  - Isolation of lipophilic compounds by countercurrent chromatography (CCC) is a
      challenge because biphasic solvent systems in which these compounds distribute
      evenly are difficult to obtain. In this article we present novel applications of
      lipid compound isolation from natural sources. Conjugated linolenic acids (CLnAs,
      log KOW ~7) were isolated from pomegranate oil using a solvent system consisting
      of n-heptane/methanol/water 100:91:9 (v/v/v). The CLnA fraction was free of other
      fatty acids but consisted of different isomers which were not resolved from each
      other. In the less polar range (log KOW ~12), three tocotrienols (alpha-, gamma-
      and delta-tocotrienol) were isolated from a vitamin E capsule produced from palm
      oil by using the solvent system n-hexane/acetonitrile/benzotrifluoride (BTF) at a
      ratio of 10:6.5:3.5 (v/v/v). Between 36 and 65mg of each of the three
      tocotrienols were obtained in one injection with purities >97%. Advantages and
      disadvantages of the "BTF system" are discussed by comparing the phase
      composition with the simple n-hexane/acetonitrile system and by the fractionation
      of phytosterols (log KOW ~9.5) from rapeseed oil.

PMID- 28456360
TI  - Concentrically packed high flow air sampler for parts-per-trillion volatile and
      semi-volatile organica compounds.
AB  - Rapid determination of trace level (parts-per-trillion) volatile organic
      compounds cannot always be achieved with conventional analytical techniques. In
      this study, a device was developed to sample a large volume of air in a short
      time period. The basic design involves packing sorbent layers concentrically
      around an empty permeable tube. Single digit parts-per-trillion detection limits
      were reached in less than 25min with this sampling system using gas
      chromatography-mass spectrometry for analysis. The concentric packed trap can
      sample at high flow rates (>10L/min) because it has a large sampling surface
      cross-section and short combined sorbent bed. Additionally, the large sorbent
      amount (>1g) provides large breakthrough volume (>100L) required to achieve low
      detection limits. The trapped analytes were thermally desorbed and transferred
      into a needle trap device for final analysis. This high flow sampling system was
      explored for detection of low ppt benzene, toluene, ethylbenzene and xylenes
      (BTEX) in air.

PMID- 28456361
TI  - In the eye of the beholder.

PMID- 28456362
TI  - Pericardial interstitial cell senescence responsible for pericardial structural
      remodeling in idiopathic and postsurgical constrictive pericarditis.
AB  - OBJECTIVE: Idiopathic and postsurgical constrictive pericarditis is characterized
      by pericardial structural remodeling that involves fibrosis, calcification, and
      inflammation. This study aimed to determine whether cell senescence was
      responsible for pericardial structural remodeling. METHODS: Pericardial
      interstitial cells derived from patients with idiopathic or postsurgical
      pericarditis (pericarditis cells) were harvested. Timing of senescence and
      differences in telomere length were compared between age- and sex-matched
      controls (nonpericarditis cells). Pericardial interstitial cells derived from
      normal pericardia were serially passaged until senescence (senescent cells).
      Apoptosis, collagen matrix, calcium deposition, chemoattractant properties, gene
      expression profiles, and paracrine effects of senescent cells were compared with
      nonsenescent cells of passage 2 (nonsenescent cells). RESULTS: Pericarditis cells
      displayed senescent changes, including short telomere length, large flattened
      cell sizes, positive staining for senescence-associated beta-galactosidase, and
      limited growth capacity. These senescent cells were resistant to apoptosis,
      produced more collagen matrix, deposited more calcium, and attracted more
      monocytes/lymphocytes than the nonsenescent cells. A cluster of genes involved in
      extracellular matrix deposition (connective tissue growth factor, fibronectin,
      collagen type I, collagen type III, and tissue inhibitors of metalloproteinase
      1), calcium deposition (osteopontin, bone sialoprotein, osteonectin, and matrix
      Gla protein), and inflammatory cell recruitment (interleukin-6, chemoattractant
      protein-1, and tumor necrosis factor-alpha) were upregulated in senescent cells,
      whereas extracellular matrix-degrading enzyme (metalloproteinase-1 and
      metalloproteinase-3) was downregulated. Furthermore, senescent cells had the
      ability to promote the proliferation, differentiation, and senescence of
      neighboring cells. CONCLUSIONS: These findings suggest that senescent cells have
      characteristics promoting pericardial structural remodeling, but further work is
      needed to establish causation.

PMID- 28456363
TI  - Aortic homograft replacement in a patient with a porcelain aorta: A case report.

PMID- 28456364
TI  - Saphenous vein graft patency and fountain of youth.

PMID- 28456365
TI  - Medication management after intramedullary nailing of atypical fractures.
AB  - Long term use of bisphosphonates (BPs) in osteoporotic patients may be associated
      with stress fractures of the sub-trochanteric and shaft area of the femur, so
      called "atypical" femoral fractures (AFF). Specific diagnosis criteria have been
      defined with 5 major features; the presence of four of them characterizes the
      AFF. Once a complete fracture occurred, the best surgical treatment is closed
      reduction and intra medullary nailing. The BPs treatment should be stopped
      immediately after an AFF occurred. Dietary calcium and vitamin D status should be
      assessed, and adequate supplementation prescribed. Principle of combination of a
      systematic bone anabolic treatment is strongly debated. The recombinant
      parathyroid hormone 1-34 or Teriparatide (r) (TPTD) has an anabolic effect on
      bone and prevent osteoporotic fractures. Available preclinical and clinical data
      have also demonstrated the role played by TPTD to enhance bone fracture healing
      and the potential beneficial effect in impaired fracture healing or specific
      clinical condition like AFFs. Some authors have proposed in incomplete BP use
      stress fractures different medical management according the MRI findings. Bone
      anabolic agents may be promising both to prevent healing complications in AFFs
      and to promote healing in conservative treatment of incomplete AFFs. More
      clinical studies are needed to confirm this hypothesis.

PMID- 28456366
TI  - Validation of a new classification system for interprosthetic femoral fractures.
AB  - Interprosthetic femoral fracture (IFF) incidence is gradually increasing as the
      population is progressively ageing. However, treatment remains challenging due to
      several contributing factors, such as poor bone quality, patient comorbidities,
      small interprosthetic fragment, and prostheses instability. An effective and
      specific classification system is essential to optimize treatment management,
      therefore diminishing complication rates. This study aims to validate a
      previously described classification system for interprosthetic femoral fractures.

PMID- 28456368
TI  - Bone penetrance of locally administered vancomycin powder in a rat femur fracture
      model.
AB  - INTRODUCTION: Locally delivered, crystalline vancomycin has been suggested as a
      potential prophylactic measure against the development of deep and superficial
      surgical site infection. Clinical expectations regarding the duration and peak of
      drug concentration in local tissues following administration are unknown. Our
      goal was to develop concentration vs time curves for locally administered
      vancomycin powder in a high-energy, open femur fracture rat model in local
      tissues and to compare that data to two well performed similar, systemic
      administration studies. METHODS: After approval for animal research, 24 adult
      Sprague-Dawley rats sustained closed, midshaft femoral fracture under anesthesia.
      Fractures were caused via blunt guillotine with 750g metal rod dropped 50cm.
      Injured hindlimbs were surgically opened at fracture to simulate open injury and
      stabilized using 0.054 Kirschner wires. Vancomycin powder was administered using
      weight-based protocol (goal: 25mg/kg). Rats were sacrificed in groups of 4 at 4,
      8, 24, 48, 72, 96h. Samples harvested included rat-tail venous blood prior to
      sacrifice, and femoral bone and anterior thigh soft-tissue were harvested post
      mortem. High Performance Liquid Chromatography (HPLC) was performed on all
      samples. RESULTS: Concentration vs. time curves demonstrated that the surrounding
      soft-tissues demonstrated highest maximum concentration (1.5mg vancomycin/g
      muscle). Bone reached maximum average of 199MUg vancomycin/g femur: approximately
      13% of maximal soft-tissue absorption. Plasma reached maximum concentration of
      1.8MUg/mL plasma. All peaks at t=4h. Within 48h, average muscle vancomycin
      concentration dropped to 3MUg/g muscle (0.2% maximum muscle concentration) and
      the average bone concentration dropped to 1.9MUg/g femur (0.9% maximum bone
      concentration). Vancomycin was undetectable on all samples at 96h. Comparison to
      classical animal studies suggest local delivery to bone exceeds that of IV dosing
      for approximately 48h and may peak near concentrations of 102 multiples.
      CONCLUSIONS: Locally administered vancomycin provides drug delivery in excess of
      IV dosing for approximately 48h after intervention. Exponential decay
      demonstrates rapid removal of drug to near undetectable levels in bone, plasma,
      and local soft tissue thereafter in a rat model. Local delivery may generate
      concentrations exceeding that achievable by steady state systemic dosing for 48h.

PMID- 28456367
TI  - Inflammatory response after nailing.
AB  - Intramedullary nailing, as the gold standard stabilisation method of most long
      bones, has been tailed by its extensive use as the basic tool of investigating
      the immune response to trauma in many large and small animal models, as well as
      at the clinical setting. Over the last few decades a complex map of interactions
      between pro and anti-inflammatory pathways has been the result of these
      significant global research efforts. Parallel to the evolution of modern nailing
      and reaming techniques, significant developments at the fields of other
      disciplines relevant to trauma care, has improved the contemporary management of
      injured patients, challenging previous concepts and altering clinical barriers.
      The current article aims to summarise the current understanding of the effect of
      instrumenting the medullary canal after trauma, and hint on potential future
      directions.

PMID- 28456369
TI  - Effects of sociodemographic, treatment variables, and medical characteristics on
      quality of life of patients with maxillectomy restored with obturator prostheses.
AB  - STATEMENT OF PROBLEM: Restoration of maxillary defects resulting from tumor
      ablative surgery presents a difficult challenge, with both functional and
      esthetic issues. Whether rehabilitation with an obturator prosthesis could
      significantly contribute to improved quality of life in patients with maxillary
      resection has been scarcely studied, with relatively small study samples.
      PURPOSE: The purpose of this survey study was to assess the overall functioning
      of the obturator prosthesis and the effect of specific sociodemographic, medical,
      and treatment variables on obturator functioning and quality of life in patients
      with maxillectomy. MATERIAL AND METHODS: Global quality of life (QOL) and
      satisfaction with the obturator prosthesis of 57 patients who underwent
      maxillectomy and prosthetic rehabilitation at the National and Kapodistrian
      University of Athens were assessed using 3 questionnaires: European Organization
      for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30
      (QLQ-C30), the EORTC QLQ-HN35, and the obturator functioning scale. The data were
      analyzed using the Kruskal-Wallis 1-way ANOVA on ranks, hierarchical multiple
      regression analysis, and the Spearman rank order correlation (alpha=.05).
      RESULTS: Satisfactory functioning of the obturator prosthesis was the most
      significant predictor of improved QOL (P<.05). QOL was significantly related to
      additional treatments (P<.05), the size of the primary tumor (P<.05), and the
      size of the maxillectomy defect (P<.05). The most significant predictors of good
      obturator functioning were additional treatments (P<.01), age at the time of
      surgery (P<.05), presence of mandibular teeth (P<.05), and previous maxillary
      removable prosthetic experience (P<.05). Obturator functioning scale appearance
      and insertion subscales (r=0.47, P<.01), followed by speech (r=0.42, P<.01), were
      significantly related to better QOL. CONCLUSIONS: A well-functioning obturator
      prosthesis was the most significant determinant for improved QOL in patients with
      maxillary resection. Age at the time of surgery, adjuvant treatments, presence of
      mandibular teeth, and previous maxillary removable prosthetic experience were the
      most significant predictors for better obturator functioning, whereas the size of
      the maxillectomy defect had a significant effect on QOL but did not influence the
      functional outcome.

PMID- 28456370
TI  - An iris positioning device and centering approach: A technique.
AB  - For patients who have lost an eye as result of trauma or a carcinoma, accurate
      replacement with an ocular prosthesis that is symmetrical to the natural eye is
      essential. This report describes a technique for recording the measurement and
      position of the iris of the natural eye and accurately transferring it to the
      prosthetic eye of the patient. The technique is both straightforward and
      accurate.

PMID- 28456371
TI  - Managing complications resulting from limited prosthetic space with a monolithic,
      multichromatic CAD-CAM implant-retained overdenture: A dental technique.
AB  - This article proposes a 2-visit clinical protocol to manage prosthodontic
      complications resulting from limited prosthetic space, using a monolithic,
      multichromatic computer-aided design and computer-aided manufacturing (CAD-CAM)
      acrylic resin implant overdenture. The advantages and limitations of using this
      approach are outlined and discussed.

PMID- 28456373
TI  - Book: Genetics for obstetricians and gynaecologists: Chapter: Genetic markers on
      ultrasound scan.
AB  - Prenatal diagnosis is a rapidly evolving speciality. Screening for aneuploidy
      begins with non-sonographic features of background risk of maternal age and past
      and family history. It is possible to diagnose major structural defects in the
      foetus using second trimester scans. Serum biochemistry markers in the early
      second trimester were added to increase the detection rate of aneuploidy.
      However, as some of these abnormalities were amenable to detection earlier in the
      first trimester, newer modalities were introduced. Nuchal translucency (NT)
      measurement was one of the main advances with regard to first trimester
      screening. Additional markers such as the presence of nasal bone, tricuspid
      regurgitation, ductus venosus and megacystis; together with first trimester serum
      biochemistry, further enhanced the detection rate of chromosomal abnormalities.
      Advances in research and technology have resulted in the availability of non
      invasive prenatal testing from 10 weeks of gestation. This has facilitated the
      detection of the three major chromosomal aneuploidies at very early gestation.
      However, there are a wide range of genetic syndromes that are not confined to the
      main trisomies. There are specific markers on ultrasound that can be linked to
      specific syndromes. Hence, a structured and stepwise approach is needed to
      identify and reach a possible diagnosis. As anomalies are classified into
      malformations, deformations and disruptions, it is important to note that not all
      markers detected are due to genetic syndromes and not all genetic syndromes can
      be detected on ultrasound scan. In this chapter, we outline common structural
      markers and their association with main genetic syndromes.

PMID- 28456375
TI  - Rolipram improves facilitation of contextual fear extinction in the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease.
AB  - Cognitive impairment often occurs in Parkinson's disease (PD), but the mechanism
      of onset remains unknown. Recently, we reported that PD model mice produced by 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) show facilitation of
      hippocampal memory extinction, which may be the cause of cognitive impairment in
      PD. When we examined the cAMP/CREB signaling in the hippocampus, decreased levels
      of cAMP and phosphorylated CREB were observed in the dentate gyrus (DG) of MPTP
      treated mice. Administration of rolipram improved the memory deficits with
      concomitant recovery of cAMP and phosphorylated CREB levels, suggesting that
      reduced cAMP/CREB signaling in the DG leads to cognitive impairment in MPTP
      treated mice.

PMID- 28456372
TI  - Uterine peristalsis and fertility: current knowledge and future perspectives: a
      review and meta-analysis.
AB  - Although uterine contractions in the non-pregnant uterus have been studied
      extensively, the knowledge gained has not been used in general fertility
      treatment work-up. In this review paper, we provide an overview of the current
      knowledge on uterine peristalsis (UP), based on the available literature. This
      literature shows that UP influences pregnancy chances in both natural and
      artificial cycles. Although the physiological background of these contractions is
      not completely clear, we know that several factors can be of influence, like
      uterine pathologies and hormones. Several options to alter pregnancy outcome by
      interfering with uterine contractions have been studied. Our meta-analysis on
      therapeutic options shows positive results of progesterone at time of embryo
      transfer in IVF cycles or prostaglandins at time of intrauterine insemination,
      although the quality of evidence is low. These therapies are probably most
      beneficial in selected groups of patients with abnormal contraction patterns. The
      introduction of an objective and user-friendly UP measuring tool suitable for use
      in daily practice would make it possible to identify and monitor these patients.
      We suggest that future research should focus on the physiology of initiation of
      UP and on the development of an effective standard measuring tool.

PMID- 28456374
TI  - PDI family protein ERp29 recognizes P-domain of molecular chaperone calnexin.
AB  - Endoplasmic reticulum (ER) resident lectin chaperone calnexin (CNX) and
      calreticulin (CRT) assist folding of nascent glycoproteins. Their association
      with ERp57, a member of PDI family proteins (PDIs) which promote disulfide bond
      formation of unfolded proteins, has been well documented. Recent studies have
      provided evidence that other PDIs may also interact with CNX and CRT.
      Accordingly, it seems possible that the ER provides a repertoire of CNX/CRT-PDI
      complexes, in order to facilitate refolding of various glycoproteins. In this
      study, we examined the ability of PDIs to interact with CNX. Among them ERp29 was
      shown to interact with CNX, similarly to ERp57. Judging from the dissociation
      constant, its ability to interact with CNX was similar to that of ERp57. Results
      of further analyses by using a CNX mutant imply that ERp29 and ERp57 recognize
      the same domain of CNX, whereas the mode of interaction with CNX might be
      somewhat different between them.

PMID- 28456376
TI  - [Consultation liaison during the peripartum: Network care between liaison and
      mobile unit].
AB  - OBJECTIVES: The pregnancy periods of peripartum and immediate postpartum
      represent moments of opportunity to access care. Both prevention and therapeutic
      management can be offered with a better chance of success during these periods.
      Our specific Consultation Liaison (CL) team PPUMMA was created in order to
      respond to the need for early detection of psychopathology and rapid
      implementation of therapeutic management and preventive measure for mother and
      child. The importance of urgently intervening "on site" seemed a necessity since
      duration of hospitalization in maternity wards is very short. Women might not
      know or understand their symptoms or be ready to ask for a referral for
      themselves but could be ready to respond positively to a team approach where the
      psychiatrist is part of the Ob-Gyn department. Working with an interdisciplinary
      approach tends to lower stress linked to the psychiatric side of the consultation
      and stigma related to psychological or psychiatric issues; therefore, PPUMMA
      intervenes within 48 to 72hours of birth. It deals with assessment and diagnosis
      during the peripartum period and orientation and referral for both mother and
      infant when necessary after birth. The Perinatal Psychiatry emergency mobile unit
      PPUMMA was created in order to address these issues. METHODS: From 2008 to 2015,
      1907 patients were assessed but data were missing for 90 patients. We therefore
      analyzed 1817 patient files looking at age, diagnosis origin of referral, time of
      referral (pre or postpartum) and delay from referral to assessment. RESULTS: Most
      patients were between 20 and 40 (81.5 %). One hundred and eighteen patients were
      under 20 years of age, of whom 64 were minors (3.5 %), and 218 were 40 or more
      (12 %). These two groups were over-represented close to threefold when comparing
      with national birth data records. A psychologist had first seen three out of four
      women. Midwives and Ob-Gyn referred 9 % and 8 % of patients while Social workers
      sent in 4 %. Two thirds of the women were seen during pregnancy, 50 % were seen
      the same day and 80 % received a consultation within 72hours. Three out of five
      of women had an assessment that concluded in a "Neurotic, stress-related and
      somatoform disorders" type code disorder linked to stress and somatoform disorder
      in ICD 10 (F40-F49). This is due to a high number (47.2 %) of F43 "Reaction to
      severe stress, and adjustment disorders". Twentynine present of women had a mood
      disorder (F30-39), and close to one third (31.6 %) had a personality disorder
      diagnosis attached. Schizophrenia, schizotypal and delusional disorders (F20-F29)
      represented 4.4 % of diagnoses. One third of the population had comorbid
      disorders: meeting either two (28.5 %) or three (3.7 %) diagnostic criteria for a
      psychiatric disorder. Most co-morbidity is due to personality disorder (82 % F60
      F69). CONCLUSION: The number of referrals and diagnostic criteria met show how
      essential a psychiatric CL team assessing and orienting women during pregnancy
      and immediate postpartum is. Opportunity for adaptation of treatment during the
      peripartum period and more long-term tailored management of disorders can be
      organized during this period in a multidisciplinary approach. Knowing how
      essential maternal mental health is for women, for infant development and for
      mother-infant interactions, this is a unique window for access to care and
      intervention. Maternal mental health is a public health issue. Access to
      psychiatric assessment and care during the peripartum period offers unique
      possibilities for prevention and care.

PMID- 28456377
TI  - Highlights from the Society of Gynecologic Oncology 2017 Annual Meeting on
      Women's Cancer.

PMID- 28456378
TI  - High glucocorticoid receptor expression predicts short progression-free survival
      in ovarian cancer.
AB  - OBJECTIVE: To investigate the association of tumor glucocorticoid receptor (GR)
      expression and patient outcome in ovarian cancer. METHODS: GR expression was
      evaluated by immunohistochemistry using tissue microarrays of specimens from 481
      patients with ovarian cancer and 4 patients with benign conditions. Low GR
      expression was defined as an intensity of 0 or 1+ and high GR as 2+ or 3+ in >1%
      of tumor cells. Analyses were performed to evaluate the relationship of GR
      expression with clinical characteristics, progression-free survival (PFS) and
      overall survival (OS). RESULTS: GR protein was highly expressed in 133 of 341
      (39.0%) tumors from patients who underwent upfront cytoreduction surgery followed
      by adjuvant chemotherapy. High GR expression was more common in serous tumors
      (p<0.001), high grade tumors (p<0.001), and advanced stage tumors (p=0.037).
      Median PFS was significantly decreased in cases with high GR (20.4months)
      compared to those with low GR (36.0months, HR=1.66, 95% CI 1.29-2.14, p<0.001).
      GR remained an independent prognostic factor for PFS in multivariate analysis. OS
      was not associated with GR status. CONCLUSIONS: These data suggest that high GR
      expression correlates with poor prognosis and support the hypothesis that
      modulating GR activity in combination with chemotherapy may improve outcomes.

PMID- 28456381
TI  - High prevalence and moderate diversity of Pseudomonas aeruginosa in the U-bends
      of high-risk units in hospital.
AB  - The presence of P. aeruginosa in water supply is clearly identified as a risk
      factor for P. aeruginosa infection in critical care units, even if routes of
      transmission are often unclear and remain a matter of debate. We determined here
      the frequency of U-bends contaminated with P. aeruginosa in high-risk units and
      described the population structure of this opportunistic pathogen in a non
      outbreak situation. Eighty-seven U-bends from sinks of rooms in five wards were
      sampled 3 times and P. aeruginosa was detected in 121 of the 261 (46.4%) U-bend
      samples. We genotyped 123 P. aeruginosa isolates with pulsed-field gel
      electrophoresis and multilocus sequence typing and found 41 pulsotypes
      distributed in 21 Sequence Types (STs). Seven major ST (ST111, CC235, CC253,
      ST520, ST539, ST1216, and ST1725) were overrepresented in the collection,
      including the high-risk clones ST111, CC253, and CC235. The distribution of the
      21 STs in the cladogram of the species was uneven with most major STs clustering
      into 2 clades. The major STs were found in different units and buildings and
      could be represented by a high diversity of pulsotypes. Altogether, this suggests
      a long term presence of P. aeruginosa in the hospital water network, possibly
      contaminated by the distribution water or by plumbing fittings before putting
      into service. Analysis of resistance rates showed that the deficiency of porin
      OprD was very frequent in U-bends isolates that may benefit from this resistance
      mechanism in hospital water fittings. In conclusion, our study demonstrates that
      U-bends of high-risk units are very frequently contaminated with P. aeruginosa
      with a moderate genomic diversity and with an over-representation of adapted
      clones.

PMID- 28456380
TI  - A Basic ApoE-Based Peptide Mediator to Deliver Proteins across the Blood-Brain
      Barrier: Long-Term Efficacy, Toxicity, and Mechanism.
AB  - We have investigated delivery of protein therapeutics from the bloodstream into
      the brain using a mouse model of late-infantile neuronal ceroid lipofuscinosis
      (LINCL), a lysosomal disease due to deficiencies in tripeptidyl peptidase 1
      (TPP1). Supraphysiological levels of TPP1 are delivered to the mouse brain by
      acute intravenous injection when co-administered with K16ApoE, a peptide that in
      trans mediates passage across the blood-brain barrier (BBB). Chronic treatment of
      LINCL mice with TPP1 and K16ApoE extended the lifespan from 126 to >294 days,
      diminished pathology, and slowed locomotor dysfunction. K16ApoE enhanced uptake
      of a fixable biotin tracer by brain endothelial cells in a dose-dependent manner,
      suggesting that its mechanism involves stimulation of endocytosis.
      Pharmacokinetic experiments indicated that K16ApoE functions without disrupting
      the BBB, with minimal effects on overall clearance or uptake by the liver and
      kidney. K16ApoE has a narrow therapeutic index, with toxicity manifested as
      lethargy and/or death in mice. To address this, we evaluated variant peptides but
      found that efficacy and toxicity are associated, suggesting that desired and
      adverse effects are mechanistically related. Toxicity currently precludes direct
      clinical application of peptide-mediated delivery in its present form but it
      remains a useful approach to proof-of-principle studies for biologic therapies to
      the brain in animal models.

PMID- 28456382
TI  - A rare complication of vomiting in pregnancy: Wernicke encephalopathy.

PMID- 28456383
TI  - Adult-onset spinal muscular atrophy: An update.
AB  - Spinal muscular atrophy (SMA) refers to a group of disorders affecting lower
      motor neurons. The age of onset of these disorders is variable, ranging from the
      neonatal period to adulthood. Over the last few years, there has been enormous
      progress in the description of new genes and phenotypes that throw new light on
      the molecular pathways involved in motor neuron degeneration. Advances in our
      understanding of the pathophysiology of the most frequent forms, SMA linked to
      SMN1 gene mutations and Kennedy disease, has led to the development of
      therapeutic strategies currently being tested in clinical trials. This report
      provides a general overview of the clinical features and pathophysiological
      mechanisms in adult-onset genetic SMA disorders in which the causative gene has
      been identified (SMN1-related SMA, Kennedy disease, CHCHD10, TRPV4, DYNC1H1 and
      BICD2). Sporadic lower motor neuron disease, also known as progressive muscular
      atrophy (PMA), is also discussed. The finding of TDP-43 aggregates in
      immunohistochemical studies of PMA strongly supports the idea that it is a
      phenotypic variant of amyotrophic lateral sclerosis (ALS).

PMID- 28456379
TI  - Chimeric Antigen Receptors: A Cell and Gene Therapy Perspective.
AB  - Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T
      lymphocytes to target chosen antigens. The targeting of CD19, a cell surface
      molecule expressed in the vast majority of leukemias and lymphomas, has been
      successfully translated in the clinic, earning CAR therapy a special distinction
      in the selection of "cancer immunotherapy" by Science as the breakthrough of the
      year in 2013. CD19 CAR therapy is predicated on advances in genetic engineering,
      T cell biology, tumor immunology, synthetic biology, target identification, cell
      manufacturing sciences, and regulatory compliance-the central tenets of CAR
      therapy. Here, we review two of these foundations: the genetic engineering
      approaches and cell types to engineer.

PMID- 28456384
TI  - Evidence of presynaptic dopaminergic dysfunction in acute methanol intoxication.

PMID- 28456385
TI  - Changes in Red Blood Cell membrane lipid composition: A new perspective into the
      pathogenesis of PKAN.
AB  - Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of
      Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations
      in the pantothenate kinase 2 gene (PANK2). The PANK2 catalyzes the first step of
      coenzyme A (CoA) biosynthesis, a pathway producing an essential cofactor that
      plays a key role in energy and lipid metabolism. The majority of PANK2 mutations
      reduces or abolishes the activity of the enzyme. In around 10% of cases with
      PKAN, the presence of deformed red blood cells with thorny protrusions in the
      circulation has been detected. Changes in membrane protein expression and
      assembly during erythropoiesis were previously explored in patients with PKAN.
      However, data on red blood cell membrane phospholipid organization are still
      missing in this disease. In this study, we performed lipidomic analysis on red
      blood cells from Italian patients affected by PKAN with a particular interest in
      membrane physico-chemical properties. We showed an increased number of small red
      blood cells together with membrane phospholipid alteration, particularly a
      significant increase in sphingomyelin (SM)/phosphatidylcholine (PC) and
      SM/phosphatidylethanolamine (PE) ratios, in subjects with PKAN. The membrane
      structural abnormalities were associated with membrane fluidity perturbation.
      These morphological and functional characteristics of red blood cells in patients
      with PKAN offer new possible tools in order to shed light on the pathogenesis of
      the disease and to possibly identify further biomarkers for clinical studies.

PMID- 28456386
TI  - Personality and Performance in Specific Neurocognitive Domains Among Older
      Persons.
AB  - OBJECTIVE: Certain Big 5 personality dimensions have been repeatedly linked to
      global measures of cognitive function and outcome categories. We examined whether
      the Big 5 or their specific components showed differential evidence of
      associations with specific neurocognitive domains. METHODS: Participants were 179
      older adults (70+) from a broader study on cognitive aging. The NEO-Five Factor
      Inventory and a comprehensive battery of neuropsychological tests were used.
      RESULTS: Adjusted for age, gender, and years of education, probability values,
      Bayes Factors, and measures effect size from linear models suggested strong
      evidence for associations between better delayed recall memory and higher
      Conscientiousness (principally the facets of Goal-Striving and Dependability) and
      Openness (specifically the Intellectual Interest component). Better executive
      function and attention showed moderate to strong evidence of associations with
      lower Neuroticism (especially the Self-conscious Vulnerability facet) and higher
      Conscientiousness (mostly the Dependability facet). Better language functioning
      was linked to higher Openness (specifically, the Intellectual Interests facet).
      Worse visual-spatial function was strongly associated with higher Neuroticism.
      CONCLUSION: Different tests of neurocognitive functioning show varying degrees of
      evidence for associations with different personality traits. Better understanding
      of the patterning of neurocognitive-personality linkages may facilitate grasp of
      underlying mechanisms and/or refine understanding of co-occurring clinical
      presentation of personality traits and specific cognitive deficits.

PMID- 28456390
TI  - Dementia in the workplace.

PMID- 28456388
TI  - Risk Factors for Delayed Referral to a Craniofacial Specialist for Treatment of
      Craniosynostosis.
AB  - OBJECTIVE: To assess the impact of age at referral on treatment options in
      craniosynostosis and to identify risk factors for referral delays in this
      population. STUDY DESIGN: A retrospective cohort study was performed on patients
      with an abnormal head shape diagnosis treated at a single academic medical center
      between January 1, 2004 and January 1, 2014. Newly diagnosed patients with
      craniosynostosis were identified and referral patterns were examined. A
      multivariate logistic regression model was used to identify risk factors
      associated with the range of ages at initial referral. RESULTS: A total of 477
      patients were evaluated at our institution, 197 of whom were subsequently
      diagnosed with craniosynostosis. The median age at initial appointment was 5.6
      months (mean 8.2 months). Only 28% of children were referred within 3 months of
      birth. Patients referred within 3 months of birth were less likely to have had
      preappointment imaging than those patients referred slightly later (OR 2.53, CI
      1.07-5.98, P = .035). Several variables were associated with referral after 12
      months of age including multiple suture involvement (OR 4.21, CI 1.06-16.68, P =
      .041), minority race (OR 4.96, CI 1.91-12.9, P  <= .0001), and referral by a
      nonpediatrician (OR 6.9, CI 1.73-27.49, P = .006). CONCLUSIONS: Obtaining imaging
      before referral to a specialist for abnormal head shape was associated with a
      delay in evaluation and potentially increases radiation exposure and limits
      treatment options in patients with craniosynostosis. In addition, children from
      minority groups, children referred from someone other than a pediatrician's
      office, and those with multiple suture craniosynostosis are at increased risk of
      delayed referral. Further studies into the cause of these delays are warranted.

PMID- 28456387
TI  - Erythropoietin and Brain Magnetic Resonance Imaging Findings in Hypoxic-Ischemic
      Encephalopathy: Volume of Acute Brain Injury and 1-Year Neurodevelopmental
      Outcome.
AB  - : In the Neonatal Erythropoietin and Therapeutic Hypothermia Outcomes study, 9/20
      erythropoietin-treated vs 12/24 placebo-treated infants with hypoxic-ischemic
      encephalopathy had acute brain injury. Among infants with acute brain injury, the
      injury volume was lower in the erythropoietin than the placebo group (P = .004).
      Higher injury volume correlated with lower 12-month neurodevelopmental scores.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT01913340.

PMID- 28456389
TI  - Development of Reliable and Validated Tools to Evaluate Technical Resuscitation
      Skills in a Pediatric Simulation Setting: Resuscitation and Emergency Simulation
      Checklist for Assessment in Pediatrics.
AB  - OBJECTIVES: To develop a reliable and validated tool to evaluate technical
      resuscitation skills in a pediatric simulation setting. STUDY DESIGN: Four
      Resuscitation and Emergency Simulation Checklist for Assessment in Pediatrics
      (RESCAPE) evaluation tools were created, following international guidelines:
      intraosseous needle insertion, bag mask ventilation, endotracheal intubation, and
      cardiac massage. We applied a modified Delphi methodology evaluation to binary
      rating items. Reliability was assessed comparing the ratings of 2 observers (1 in
      real time and 1 after a video-recorded review). The tools were assessed for
      content, construct, and criterion validity, and for sensitivity to change.
      RESULTS: Inter-rater reliability, evaluated with Cohen kappa coefficients, was
      perfect or near-perfect (>0.8) for 92.5% of items and each Cronbach alpha
      coefficient was >=0.91. Principal component analyses showed that all 4 tools were
      unidimensional. Significant increases in median scores with increasing levels of
      medical expertise were demonstrated for RESCAPE-intraosseous needle insertion (P
      = .0002), RESCAPE-bag mask ventilation (P = .0002), RESCAPE-endotracheal
      intubation (P = .0001), and RESCAPE-cardiac massage (P = .0037). Significantly
      increased median scores over time were also demonstrated during a simulation
      based educational program. CONCLUSIONS: RESCAPE tools are reliable and validated
      tools for the evaluation of technical resuscitation skills in pediatric settings
      during simulation-based educational programs. They might also be used for medical
      practice performance evaluations.

PMID- 28456391
TI  - Optic ataxia and the dorsal visual steam re-visited: Impairment in bimanual
      haptic matching performed without vision.
AB  - The 'two visual systems' account proposed by Milner and Goodale (1992) argued
      that visual perception and the visual control of action depend upon functionally
      distinct and anatomically separable brain systems: a ventral stream of visual
      processing that mediates visual perception (object identification and
      recognition) and a dorsal stream of visual processing mediating visually guided
      action. Compelling evidence for this proposal was provided by the
      neuropsychological studies of brain injured patients, in particular the
      contrasting pattern of impaired and preserved visual processing abilities of the
      visual object agnostic patient [DF] and optic ataxic patients who it was argued
      presented with impaired dorsal stream function. Optic ataxia [OA] has thus become
      a cornerstone of this 'two visual system' account (Pisella et al., 2009). In the
      current study we re-examine this assumption by investigating how several
      individuals presenting with OA performed on a bimanual haptic matching task
      performed without vision, when the bar to be matched was presented haptically or
      visually. We demonstrate that, unlike neurologically healthy controls who perform
      the task with high levels of accuracy, all of the optic ataxic patients were
      unable to perform the task. We interpret this finding as further evidence that
      the key difficulty experienced by optic ataxic patients across a range of
      behavioural tasks may be an inability to simultaneously and directly compare two
      spatial representations so as to compute the difference between them.

PMID- 28456392
TI  - Asynchrony in the rubber hand paradigm: Unexpected illusions following stroke.

PMID- 28456393
TI  - Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node
      Positivity.
AB  - BACKGROUND: The optimal adjuvant treatment for cT1-2 N0 esophageal cancer
      patients found to have pathologic nodal involvement after an upfront operation is
      unclear. This study investigated the effects of postoperative chemotherapy and
      chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental
      pN+ disease stratified by margin status. METHODS: We identified cT1-2 N0 M0
      esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data
      Base. Patients were categorized as having received surgical resection alone,
      surgical resection followed by chemotherapy (S+CT), and surgical resection
      followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were
      conducted on margin-negative and margin-positive patients. Overall survival was
      compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox
      regression analysis. RESULTS: Among 443 patients, 52.6% received surgical
      resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly
      more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous
      cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT
      (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT
      (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were
      associated with significantly increased overall survival. These findings
      persisted among margin-negative patients. However, in margin-positive patients,
      S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was
      associated with significantly improved survival compared with surgical resection
      alone. CONCLUSIONS: Among cT1-2 N0 pN+ esophageal cancer patients, adjuvant
      chemotherapy may be sufficient for margin-negative patients, whereas adjuvant
      chemoradiation therapy appears necessary for margin-positive patients. Further
      prospective studies are needed to confirm the results.

PMID- 28456394
TI  - Reexamining the Role of Surgical Aortic Valve Replacement After Mediastinal
      Radiation Therapy.
AB  - BACKGROUND: The risk of aortic valve replacement (AVR) for patients after
      mediastinal radiation therapy (MRT) remains unaccounted for in traditional risk
      scores. The aim of this study was to examine perioperative and midterm outcomes
      in patients undergoing AVR after MRT in the current era. METHODS: From 2000 to
      2016, 49 consecutive patients previously exposed to MRT underwent AVR with or
      without concomitant procedures at a single center. Patients were divided into two
      groups: isolated AVR (n = 18) and AVR with concomitant procedures (n = 31). The
      logistic European System for Cardiac Operative Risk Evaluation II mean score was
      2.8% +/- 3.4% and The Society of Thoracic Surgeons mean score was 1.7% +/- 1.5%.
      Median follow-up was 6.6 years and was 90% complete within 12 months of study
      closure. RESULTS: Overall inhospital mortality was 10% (0% in the isolated group
      versus 16% in the concomitant group; p = 0.14). A total of 21 patients (47%) died
      at follow-up. Mean interval to death was 2.0 +/- 1.1 years from surgery in the
      isolated group versus 1.4 +/- 1.6 years in the concomitant group (p = 0.18).
      Actuarial survival was 93% +/- 6%, 73% +/- 11%, and 65% +/- 13%, at 1, 3, and 5
      years, respectively, in the isolated group versus 74% +/- 8%, 44% +/- 11%, and
      37% +/- 11% in the concomitant group (p = 0.03). CONCLUSIONS: Isolated AVR can be
      performed safely in patients with MRT-induced disease. In contrast, AVR with
      concomitant procedures is associated with high mortality, which is vastly
      underestimated using traditional risk scores. In both groups, survival at 5 years
      is markedly impaired.

PMID- 28456395
TI  - Quantification of Lipid Filtration and the Effects on Cerebral Injury During
      Cardiopulmonary Bypass.
AB  - BACKGROUND: Lipid microemboli (LME) are formed in pericardial suction blood
      which, when returned to the cardiopulmonary bypass (CPB) circuit, can pass
      through filter materials and are returned to the arterial cannula. LME have been
      observed to enter all major organs and have been associated with small capillary
      arteriolar dilatations in the brains of patients who have died after CPB.
      However, a causal relationship showing correlation between LME and organ
      dysfunction has not been demonstrated, or whether removal of LME results in
      improved organ function. METHODS: A prospective, single center, randomized
      controlled trial examined 30 patients (15 per group) undergoing coronary artery
      bypass grafting using CPB with or without a lipid-depleting filter. The effects
      of LME filtration on neurocognitive injury were assessed using neuron-specific
      enolase (NSE). RESULTS: The study group showed a significant reduction in LME
      after filtration of the pericardial suction blood (p < 0.001), whereas the
      control group exhibited a significant rise in LME (p < 0.001). There was a
      significant reduction in peak NSE release (p = 0.013) and significant attenuation
      throughout the postoperative period (p = 0.002). Correlation and regression
      analyses showed a significant relationship between the number of LME post-CPB and
      peak NSE release (r = 0.42, p = 0.02). CONCLUSIONS: Several methods of LME
      filtration have been proposed, but none provided a suitable, efficacious method
      for use within the clinical setting. The RemoweLL CPB system removes significant
      numbers of LME from the cardiotomy suction. Furthermore, LME correlate to the
      release of a known marker of neurologic injury.

PMID- 28456397
TI  - Erratum to "Increased STM expression is associated with drought tolerance in
      Arabidopsis" [J. Plant Physiol. 201 (2016) 79-84].

PMID- 28456396
TI  - Long-Term Outcomes of Children With Trisomy 13 and 18 After Congenital Heart
      Disease Interventions.
AB  - BACKGROUND: The purpose of this study is to report short- and long-term outcomes
      after congenital heart defect (CHD) interventions in patients with trisomy 13 or
      18. METHODS: A retrospective review of the Pediatric Cardiac Care Consortium
      (PCCC) identified children with trisomy 13 or 18 with interventions for CHD
      between 1982 and 2008. Long-term survival and cause of death were obtained
      through linkage with the National Death Index. RESULTS: A total of 50 patients
      with trisomy 13 and 121 patients with trisomy 18 were enrolled in PCCC between
      1982 and 2008; among them 29 patients with trisomy 13 and 69 patients with
      trisomy 18 underwent intervention for CHD. In-hospital mortality rates for
      patients with trisomy 13 or trisomy 18 were 27.6% and 13%, respectively. Causes
      of in-hospital death were primarily cardiac (64.7%) or multiple organ system
      failure (17.6%). National Death Index linkage confirmed 23 deaths after
      discharge. Median survival (conditioned to hospital discharge) was 14.8 years
      (95% confidence interval [CI]: 12.3 to 25.6 years) for patients with trisomy 13
      and 16.2 years (95% CI: 12 to 20.4 years) for patients with trisomy 18. Causes of
      late death included cardiac (43.5%), respiratory (26.1%), and pulmonary
      hypertension (13%). CONCLUSIONS: In-hospital mortality rate for all surgical risk
      categories was higher in patients with trisomy 13 or 18 than that reported for
      the general population. However, patients with trisomy 13 or 18, who were
      selected as acceptable candidates for cardiac intervention and who survived CHD
      intervention, demonstrated longer survival than previously reported. These
      findings can be used to counsel families and make program-level decisions on
      offering intervention to carefully selected patients.

PMID- 28456399
TI  - Prior lactose glycation of caseinate via the Maillard reaction affects in vitro
      activities of the pepsin-trypsin digest toward intestinal epithelial cells.
AB  - The well-known Maillard reaction in milk occurs between lactose and milk proteins
      during thermal treatment, and its effects on milk nutrition and safety have been
      well studied. A lactose-glycated caseinate was prepared via this reaction and
      digested using 2 digestive proteases, pepsin and trypsin. The glycated caseinate
      digest was assessed for its in vitro activities on rat intestinal epithelial
      cells in terms of growth proliferation, anti-apoptotic effect, and
      differentiation induction using caseinate digest as reference, to verify
      potential effects of the Maillard reaction on these activities of caseinate
      digest to the cells. Two digests had proliferative and anti-apoptotic effects,
      and reached the highest effects at 0.02 g/L of digest concentration with
      treatment time of 24 h. In comparison with caseinate digest, glycated caseinate
      digest always showed weaker proliferative (5.3-14.2%) and anti-apoptotic (5.9
      39.0%) effects, and was more toxic to the cells at 0.5 g/L of digest
      concentration with treatment time of 48 h. However, glycated caseinate digest at
      2 incubation times of 4 to 7 d showed differentiation induction higher than
      caseinate digest, as it could confer the cells with increased activities in
      lactase (16.3-26.6%), sucrase (22.4-31.2%), and alkaline phosphatase (17.4
      24.8%). Transmission electron microscopy observation results also confirmed
      higher differentiation induction of glycated caseinate digest. Amino acid loss
      and lactose glycation partially contributed to these decreased and enhanced
      activities of glycated caseinate digest, respectively. The Maillard reaction of
      caseinate and lactose is thus shown in this study to have effects on the
      activities of caseinate digest to intestinal epithelial cells.

PMID- 28456398
TI  - Effect of circulating exosomes from transition cows on Madin-Darby bovine kidney
      cell function.
AB  - The greatest risk of metabolic and infectious disease in dairy cows is during the
      transition from pregnancy to lactating (i.e., the transition period). The
      objective of this experiment was to determine the effects of extracellular
      vesicles (microvesicles involved in cell-to-cell signaling) isolated from
      transition cows on target cell function. We previously identified differences in
      the protein profiles of exosomes isolated from cows divergent in metabolic health
      status. Therefore, we hypothesized that these exosomes would affect target
      tissues differently. To investigate this, 2 groups of cows (n = 5/group) were
      selected based on the concentration of beta-hydroxybutyrate and fatty acids in
      plasma and triacylglycerol concentration in liver at wk 1 and 2 postcalving. Cows
      with high concentrations of beta-hydroxybutyrate, fatty acids, and
      triacylglycerol were considered at increased risk of clinical disease during the
      transition period (high-risk group; n = 5) and were compared with cows that had
      low concentrations of the selected health indicators (low-risk group; n = 5). At
      2 time points during the transition period (postcalving at wk 1 and 4), blood was
      sampled and plasma exosomes were isolated from the high-risk and low-risk cows.
      The exosomes were applied at concentrations of 10 and 1 ug/mL to 5 * 103 Madin
      Darby bovine kidney cells grown to 50% confluence in 96-well plates. Results
      indicate a numerical increase in cell proliferation when exosomes from high-risk
      cows were applied compared with those from low-risk cows. Consistent with an
      effect on cell proliferation, quantitative reverse transcriptase PCR indicated a
      trend for upregulation of 3 proinflammatory genes (granulocyte colony-stimulating
      factor, ciliary neurotrophic factor, and CD27 ligand) with the application of
      high-risk exosomes, which are involved in cellular growth and survival. Proteomic
      analysis indicated 2 proteins in the low-risk group that were not identified in
      the high-risk group (endoplasmin and catalase), which may also be indicative of
      the metabolic state of origin. It is likely that the metabolic state of the
      transition cow affects cellular function through exosomal messaging; however,
      more in-depth research into cross-talk between exosomes and target cells is
      required to determine whether exosomes influence Madin-Darby bovine kidney cells
      in this manner.

PMID- 28456401
TI  - Effect of source of trace minerals in either forage- or by-product-based diets
      fed to dairy cows: 2. Apparent absorption and retention of minerals.
AB  - Eighteen multiparous cows were used in a split-plot replicated Latin square with
      two 28-d periods to evaluate the effects of source of supplemental Cu, Zn, and Mn
      (sulfates or hydroxy) on apparent absorption of minerals when fed in either a
      forage- or by-product-based diet. The by-product diets were formulated to have
      greater concentrations of NDF and lesser concentrations of starch, and specific
      ingredients were chosen because they were good sources of soluble fiber and beta
      glucans, which bind trace minerals in nonruminants. We hypothesized that hydroxy
      trace minerals would interact less with digesta and have greater apparent
      absorption compared with sulfate minerals, and the difference in apparent
      absorption would be greater for the by-product diet compared with the forage
      based diet. During the 56-d experiment, cows remained on the same fiber treatment
      but source of supplemental trace mineral was different for each 28-d period;
      thus, all cows were exposed to both mineral treatments. During each period cows
      were fed no supplemental Cu, Zn, or Mn for 16 d, followed by 12 d of feeding
      supplemental minerals from either sulfate or hydroxy sources. Supplemental
      minerals for each of the mineral sources fed provided approximately 10, 35, and
      32 mg/kg of supplemental Cu, Zn, and Mn, respectively, for both fiber treatments.
      Total Cu, Zn, and Mn dietary concentrations, respectively, were approximately 19,
      65, and 70 mg/kg for the forage diets and 21, 85, and 79 for the by-product
      diets. Treatment had no effect on dry matter intake (24.2 kg/d) or milk
      production (34.9 kg/d). Cows consuming the by-product diets had greater Zn (1,863
      vs. 1,453 mg/d) and Mn (1,790 vs. 1,588 mg/d) intake compared with cows fed
      forage diets, but apparent Zn absorption was similar between treatments.
      Manganese apparent absorption was greater for the by-product diets compared with
      the forage diets (16 vs. 11%). A fiber by mineral interaction was observed for Cu
      apparent absorption, as cows fed hydroxy minerals with forage diets had greater
      apparent absorption compared with cows fed sulfate minerals; however, the
      opposite was observed with the by-product diets. Source of supplemental trace
      minerals and type of fiber in diets affected availability of Cu and Mn and should
      be considered in ration formulation.

PMID- 28456402
TI  - Distribution of non-aureus staphylococci species in udder quarters with low and
      high somatic cell count, and clinical mastitis.
AB  - The effect of non-aureus staphylococci (NAS) in bovine mammary health is
      controversial. Overall, NAS intramammary infections (IMI) increase somatic cell
      count (SCC), with an effect categorized as mild, mostly causing subclinical or
      mild to moderate clinical mastitis. However, based on recent studies, specific
      NAS may affect the udder more severely. Some of these apparent discrepancies
      could be attributed to the large number of species that compose the NAS group.
      The objectives of this study were to determine (1) the SCC of quarters infected
      by individual NAS species compared with NAS as a group, culture-negative, and
      major pathogen-infected quarters; (2) the distribution of NAS species isolated
      from quarters with low SCC (<200,000 cells/mL) and high SCC (>=200,000 cells/mL),
      and clinical mastitis; and (3) the prevalence of NAS species across quarters with
      low and high SCC. A total of 5,507 NAS isolates, 3,561 from low SCC quarters,
      1,873 from high SCC quarters, and 73 from clinical mastitis cases, were obtained
      from the National Cohort of Dairy Farms of the Canadian Bovine Mastitis Research
      Network. Of quarters with low SCC, high SCC, or clinical mastitis, 7.6, 18.5, and
      4.3% were NAS positive, respectively. The effect of NAS IMI on SCC was estimated
      using mixed-effect linear regression; prevalence of NAS IMI was estimated using
      Bayesian analyses. Mean SCC of NAS-positive quarters was 70,000 cells/mL, which
      was higher than culture-negative quarters (32,000 cells/mL) and lower than major
      pathogen-positive quarters (129,000 to 183,000 cells/mL). Compared with other NAS
      species, SCC was highest in quarters positive for Staphylococcus capitis,
      Staphylococcus gallinarum, Staphylococcus hyicus, Staphylococcus agnetis, or
      Staphylococcus simulans. In NAS-positive quarters, Staphylococcus xylosus
      (12.6%), Staphylococcus cohnii (3.1%), and Staphylococcus equorum (0.6%) were
      more frequently isolated from quarters with low SCC than other NAS species,
      whereas Staphylococcus sciuri (14%) was most frequently isolated from clinical
      mastitis cases. Finally, in NAS-positive quarters, Staphylococcus chromogenes, S.
      simulans, Staphylococcus epidermidis, and Staphylococcus haemolyticus were
      isolated with similar frequency from among low SCC and high SCC quarters and
      clinical mastitis cases. Staphylococcus chromogenes, S. simulans, S. xylosus, S.
      haemolyticus, S. epidermidis, S. agnetis, Staphylococcus arlettae, S. capitis, S.
      gallinarum, S. sciuri, and Staphylococcus warneri were more prevalent in high
      than in low SCC quarters. Because the NAS are a large, heterogeneous group,
      considering them as a single group rather than at the species, or even subspecies
      level, has undoubtedly contributed to apparent discrepancies among studies as to
      their distribution and importance in IMI and mastitis.

PMID- 28456400
TI  - Effect of denatured whey protein concentrate and its fractions on cheese
      composition and rheological properties.
AB  - The objectives of this study were (1) to assess the effect of a denatured whey
      protein concentrate (DWPC) and its fractions on cheese yield, composition, and
      rheological properties, and (2) to separate the direct effect of the DWPC or its
      fractions on cheese rheological properties from the effect of a concomitant
      increase in cheese moisture. Semihard cheeses were produced at a laboratory
      scale, and mechanical properties were characterized by dynamic rheometry.
      Centrifugation was used to induce a moisture gradient in cheese to separate the
      direct contribution of the DWPC from the contribution of moisture to cheese
      mechanical properties. Cheese yield increased and complex modulus (G*) decreased
      when the DWPC was substituted for milk proteins in milk. For cheeses with the
      same moisture content, the substitution of denatured whey proteins for milk
      proteins had no direct effect on rheological parameters. The DWPC was
      fractionated to evaluate the contribution of its different components
      (sedimentable aggregates, soluble component, and diffusible component) to cheese
      yield, composition, and rheological properties. The sedimentable aggregates were
      primarily responsible for the increase in cheese yield when DWPC was added.
      Overall, moisture content explained to a large extent the variation in cheese
      rheological properties depending on the DWPC fraction. However, when the effect
      of moisture was removed, the addition of the DWPC sedimentable fraction to milk
      increased cheese complex modulus. Whey protein aggregates were hypothesized to
      act as active fillers that physically interact with the casein matrix and confer
      rigidity after pressing.

PMID- 28456403
TI  - Factors associated with dairy calf health in automated feeding systems in the
      Upper Midwest United States.
AB  - Automated calf feeding systems are becoming more common on US dairy farms. The
      objective of this study was to evaluate calf health in these systems and to
      identify risk factors associated with adverse health outcomes on farms in the
      Upper Midwest United States. Over an 18-mo period on bimonthly farm visits to 38
      farms, calves (n = 10,179) were scored for attitude, ear, eye, and nasal health,
      as well as evidence of diarrhea (hide dirtiness score of perianal region,
      underside of the tail, and tailhead). For all health score categories, a score of
      0 represented an apparently healthy animal. Rectal temperatures were taken in
      calves scoring a >=2 in any category, and those with a temperature >39.4 degrees
      C were categorized as having a fever (n = 550). Associations were determined
      between farm-level variables and health scores to identify risk factors for
      higher (worse) scores. All health outcomes were associated with season of
      measurement, with fall and winter seasons increasing the odds of a high health
      score or detected fever. High bacterial counts measured in the milk or milk
      replacer were associated with increased odds for higher attitude and ear scores,
      and higher odds for calves having a detected fever. Higher peak milk allowance
      (L/d) was associated with lower hide dirtiness score, whereas a longer period of
      time (d) to reach peak milk allowance was associated with increased odds of
      higher scores for attitude, ear, eye, and hide dirtiness, as well as fever.
      Higher fat content in milk was associated with increased odds of high eye score.
      Less space per calf (m2/calf) was associated with higher ear and eye scores,
      whereas larger group sizes were associated with increased odds of higher nasal
      score and decreased odds of higher hide dirtiness score. Rectangular pen shape
      was associated with decreased odds of higher eye score. Absence of a positive
      pressure ventilation tube was associated with increased odds of having a calf
      detected with a fever. Based on these results, we hypothesize that these factors
      could be managed to improve health outcomes for dairy calves on automated feeding
      systems.

PMID- 28456404
TI  - Effect of pre- and postpartum supplementation with lipid-encapsulated conjugated
      linoleic acid on reproductive performance and the growth hormone-insulin-like
      growth factor-I axis in multiparous high-producing dairy cows.
AB  - The objective of the study was to evaluate the effect of prepartum and postpartum
      (PP) supplementation with 2 isomers of conjugated linoleic acid (CLA) on
      reproductive parameters and some related metabolic factors in dairy cows. High
      producing, multiparous Holstein Friesian cows (n = 60) were allotted to 3
      treatment groups: the CLA1 group (n = 20) was supplemented with 70 g of lipid
      encapsulated CLA providing 7 g each of cis-9,trans-11 and trans-10,cis-12 CLA
      from d 21 (d 21) before expected calving until d 7 after artificial insemination
      (AI), that is, until 77 to 91 d PP; the CLA2 group (n = 20) was supplemented with
      the same amount of CLA beginning at calving until d 7 after AI; and the control
      group (n = 20) received an isocaloric, isonitrogenous, and isolipidic diet. Blood
      samples were taken weekly to measure glucose, insulin, insulin-like growth factor
      I (IGF-I), and leptin. Liver biopsy was performed in 10 cows per group for growth
      hormone receptor 1A and IGF-I mRNA analyses. At d 49 to 63 PP, ovulation was
      synchronized with the Pre-Synch protocol followed by fixed-time AI. Milk
      progesterone was monitored from calving until d 35 post-AI. Cows returning to
      estrus following AI were inseminated. Supplementation with CLA before calving
      improved the recovery of plasma leptin levels in the early PP period (from the
      day of calving until wk 3 PP; treatment effect). Later PP (wk 5), plasma IGF-I,
      and leptin remained significantly higher in both CLA1 and CLA2 groups compared
      with control, although hepatocellular IGF-I mRNA was not different among groups.
      Plasma IGF-I levels remained higher in both CLA-treated groups on the day of AI.
      Growth hormone receptor 1A mRNA levels in hepatic tissue decreased in all groups,
      reaching a nadir in the first week PP. Days to first PP ovulation did not differ
      between groups; however, both supplemented groups conceived earlier compared with
      control (d 97 +/- 19, d 97 +/- 23, and d 113 +/- 30 for CLA1, CLA2, and control,
      respectively). Plasma progesterone concentration was higher in both supplemented
      groups on d 2 to 5 following the synchronized ovulation than in controls. We
      concluded that CLA supplementation around calving alters PP metabolic signals as
      reflected by higher plasma leptin and IGF-I levels. Conjugated linoleic acid
      stimulated early luteal function and reduced the PP interval to conception.

PMID- 28456405
TI  - Effects of replacing soybean meal with canola meal differing in rumen
      undegradable protein content on ruminal fermentation and gas production kinetics
      using 2 in vitro systems.
AB  - Previous research indicated that there were significant differences in rumen
      undegradable protein (RUP) among canola meals (CM), which could influence the
      nutritional value of CM. The objectives of this study were to (1) evaluate the
      effects of feeding CM with different RUP contents on ruminal fermentation,
      nutrient digestion, and microbial growth using a dual-flow continuous culture
      system (experiment 1) and (2) evaluate ruminal gas production kinetics, in vitro
      organic matter (OM) digestibility, and methane (CH4) production of soybean meal
      (SBM) and CM with low or high RUP in the diet or as a sole ingredient using a gas
      production system (experiments 2 and 3). In experiment 1, diets were randomly
      assigned to 6 fermentors in a replicated 3 * 3 Latin square. The only ingredient
      that differed among diets was the protein supplement. The treatments were (1)
      solvent-extracted SBM, (2) low-RUP solvent-extracted CM (38% RUP as a percentage
      of crude protein), and (3) high-RUP solvent-extracted CM (50% RUP). Diets were
      prepared as 3 concentrate mixtures that were combined with 25% orchardgrass hay
      and 15% wheat straw (dry matter basis). Experiments 2 and 3 had the same design
      with 24 bottles incubated 3 times for 48 h each. During the 48-h incubation, the
      cumulative pressure was recorded to determine gas production kinetics, in vitro
      OM digestibility, and CH4 production. In experiment 1, N flow (g/d), efficiency
      of N use, efficiency of bacterial N synthesis, total volatile fatty acids (mM),
      and molar proportion of acetate, propionate, and isobutyrate were not affected by
      treatments. There were tendencies for a decrease in ruminal NH3-N and an increase
      in molar proportion of butyrate for the SBM diet compared with both CM diets. The
      molar proportion of valerate was greater in both CM diets, whereas the molar
      proportion of isovalerate and total branched-chain volatile fatty acids was lower
      for the CM diets compared with the SBM diet. In experiments 2 and 3, the SBM diet
      had a greater gas pool size than both CM diets. The SBM diet increased in vitro
      OM digestibility; however, it also tended to increase CH4 production (mM and g/kg
      of DM) compared with both CM diets. Based on the results of this study, CM with
      RUP varying from 38 to 50% of crude protein does not affect ruminal fermentation,
      nutrient digestion, and microbial growth when CM is included at up to 34% of the
      diet.

PMID- 28456406
TI  - Multivariate dynamic linear models for estimating the effect of experimental
      interventions in an evolutionary operations setup in dairy herds.
AB  - Evolutionary operations is a method to exploit the association of often small
      changes in process variables, planned during systematic experimentation and
      occurring during the normal production flow, to production characteristics to
      find a way to alter the production process to be more efficient. The objective of
      this study was to construct a tool to assess the intervention effect on milk
      production in an evolutionary operations setup. The method used for this purpose
      was a dynamic linear model (DLM) with Kalman filtering. The DLM consisted of
      parameters describing milk yield in a herd, individual cows from a herd, and an
      intervention effect on a given day. The model was constructed to handle any
      number of cows, experimental interventions, different data sources, or presence
      of control groups. In this study, data from 2 commercial Danish herds were used.
      In herd 1, data on 98,046 and 12,133 milkings registered from an automatic
      milking system (AMS) were used for model building and testing, respectively. In
      herd 2, data on 3,689 milkings on test days were used for estimating the initial
      model parameters. For model testing, data from both bulk tank milk yield (85
      observations) and test-day milkings (1,471) were used. In herd 1, the manager
      wanted to explore the possibility of reducing the amount of concentrate provided
      to the cows in an AMS. In herd 2, the manager wanted to know if the milk yield
      could be increased by elevating the energy level provided to the cows in a total
      mixed ration. The experiment conducted in herd 1 was designed with a treatment
      and a control group, whereas in herd 2 we used a pretest/posttest design. The
      constructed tool provided estimates (mean and confidence intervals) for each of 3
      interventions carried out in both herds. In herd 1, we concluded that the
      reduction in concentrate amount provided in the AMS had no negative influence on
      milk yield. For herd 2, the increased level of energy had a significant positive
      effect on milk yield but only for the first intervention. In this herd, the
      effect of intervention was also evaluated for cows in the first lactation and
      without bulk tank records. The presented model proved to be a flexible and
      dynamic tool, and it was successfully applied for systematic experimentation in
      dairy herds. The model can serve as a decision support tool for on-farm process
      optimization exploiting planned changes in process variables and the response of
      production characteristics.

PMID- 28456407
TI  - Corn grain-processing method interacts with calcium salts of palm fatty acids
      supplementation on milk production and energy balance of early-lactation cows
      grazing tropical pasture.
AB  - The objective of our study was to investigate the associative effects of feeding
      Ca salts of palm fatty acids (FA) and corn grain-processing method on production,
      nutrient digestibility, energy balance, and carryover effects of early-lactation
      dairy cows grazing a tropical pasture. Treatment diets were offered from 3 to 16
      wk postpartum (treatment period), in which all cows grazed elephant grass
      (Pennisetum purpureum L. Cameroon) and treatments were added to a concentrate
      supplement. Treatments were flint corn grain-processing method either as fine
      ground (FGC) or steam-flaked (SFC) associated with Ca salts of palm FA
      supplementation either not supplemented or supplemented (CSPO). From 17 to 40 wk
      postpartum (carryover period) all cows received a common diet fed as total mixed
      ration. During the treatment period, a tendency for an interaction between CSPO
      and corn grain-processing method were observed for milk yield, milk fat yield,
      and energy-corrected milk (ECM), as CSPO caused them to increased to a greater
      extent in the FGC diet compared with the SFC diet. Furthermore, a tendency for an
      interaction between CSPO and corn grain-processing method was observed for body
      weight change, because CSPO increased body weight loss in the FGC diet but not in
      the SFC diet. The CSPO increased milk yield, milk fat yield, 3.5% fat-corrected
      milk, ECM, and cumulative milk yield compared with not supplemented. Also, CSPO
      increased energy intake, milk energy output, and energy partitioning toward milk,
      whereas reduced energy was allocated to body reserves. The SFC increased milk
      yield, ECM, milk protein yield, milk casein yield, and cumulative milk yield, and
      decreased milk urea N compared with FGC. The SFC compared with FGC also increased
      body condition score and body weight change, and increased energy partitioning
      toward body reserves. During the carryover period, an interaction between CSPO
      and corn grain-processing method was observed for milk yield, which occurred
      because CSPO maintained higher milk yield in the FGC diet but not in the SFC
      diet. Therefore, in the carryover period, the additive effect between SFC and
      CSPO that occurred in the treatment period was not maintained throughout the
      carryover period. However, CSPO increased yields of milk fat, protein, casein as
      well as fat-corrected milk and ECM. In conclusion, corn grain-processing method
      interacts with CSPO supplementation on production responses and carryover effects
      of grazing cows. When CSPO was fed in the FGC diet, milk production increased to
      a greater extent than when fed in the SFC diet, but also caused greater
      mobilization of reserves at early lactation. This suggests an interaction between
      fat supplementation and corn grain-processing method on energy partitioning of
      dairy cows. Also, both supplementation with CSPO and SFC were effective
      strategies to increase energy intake and yields of milk and milk solids. The
      carryover effect on milk production was greater for CSPO supplementation than
      corn grain-processing method, whereas feeding SFC diets had lower mobilization of
      reserves and less body weight and body condition score variation throughout
      lactation.

PMID- 28456408
TI  - Postnatal phenotype of dairy cows is altered by in vitro embryo production using
      reverse X-sorted semen.
AB  - Abnormal fetuses, neonates, and adult offspring derived by assisted reproductive
      technologies have been reported in humans and mice and have been associated with
      increased likelihood of certain adult diseases. To test the hypothesis that
      bovine females derived by assisted reproductive technologies have altered
      postnatal growth and adult function, a retrospective cohort study evaluated
      survival, growth, and production traits of offspring derived by in vitro embryo
      production (IVP) with conventional (IVP-conv) or reverse X-sorted semen (IVP
      sexed), multiple ovulation and embryo transfer, and artificial insemination (AI)
      in a large dairy herd. Live calves produced by IVP were born slightly heavier
      compared with AI calves. In addition, IVP-sexed calves had a higher cumulative
      mortality from 90 to 180 d of age compared with AI offspring. Mortality of IVP
      conv and multiple ovulation and embryo transfer offspring was intermediate and
      not different from AI or IVP-sexed offspring. The altered phenotype of offspring
      from IVP-sexed extended to adult milk production. Cows derived by IVP-sexed
      produced less milk, fat, and protein in their first lactation compared with dairy
      cows derived by AI. Additionally, females born to nulliparous dams had a distinct
      postnatal phenotype compared with offspring from parous dams even when data were
      restricted to offspring of surrogate females. In conclusion, procedures
      associated with in vitro production of embryos involving use of reverse-sorted
      spermatozoa for fertilization result in an alteration of embryonic programming
      that persists postnatally and causes an effect on milk production in adulthood.
      Thus, some benefits of reverse-sorted semen for genetic improvement may be offset
      by adverse programming events.

PMID- 28456409
TI  - Effect of fat content on the physical properties and consumer acceptability of
      vanilla ice cream.
AB  - Ice cream is a complex food matrix that contains multiple physical phases.
      Removal of 1 ingredient may affect not only its physical properties but also
      multiple sensory characteristics that may or may not be important to consumers.
      Fat not only contributes to texture, mouth feel, and flavor, but also serves as a
      structural element. We evaluated the effect of replacing fat with maltodextrin
      (MD) on select physical properties of ice cream and on consumer acceptability.
      Vanilla ice creams were formulated to contain 6, 8, 10, 12, and 14% fat, and the
      difference was made up with 8, 6, 4, 2, and 0% maltodextrin, respectively, to
      balance the mix. Physical characterization included measurements of overrun,
      apparent viscosity, fat particle size, fat destabilization, hardness, and melting
      rate. A series of sensory tests were conducted to measure liking and the
      intensity of various attributes. Tests were also conducted after 19 weeks of
      storage at -18 degrees C to assess changes in acceptance due to prolonged storage
      at unfavorable temperatures. Then, discrimination tests were performed to
      determine which differences in fat content were detectable by consumers. Mix
      viscosity decreased with increasing fat content and decreasing maltodextrin
      content. Fat particle size and fat destabilization significantly increased with
      increasing fat content. However, acceptability did not differ significantly
      across the samples for fresh or stored ice cream. Following storage, ice creams
      with 6, 12, and 14% fat did not differ in acceptability compared with fresh ice
      cream. However, the 8% fat, 6% MD and 10% fat, 4% MD ice creams showed a
      significant drop in acceptance after storage relative to fresh ice cream at the
      same fat content. Consumers were unable to detect a difference of 2 percentage
      points in fat level between 6 and 12% fat. They were able to detect a difference
      of 4 percentage points for ice creams with 6% versus 10%, but not for those with
      8% versus 12% fat. Removing fat and replacing it with maltodextrin caused minimal
      changes in physical properties in ice cream and mix and did not change consumer
      acceptability for either fresh or stored ice cream.

PMID- 28456410
TI  - Detection and assessment of copy number variation using PacBio long-read and
      Illumina sequencing in New Zealand dairy cattle.
AB  - Single nucleotide polymorphisms have been the DNA variant of choice for genomic
      prediction, largely because of the ease of single nucleotide polymorphism
      genotype collection. In contrast, structural variants (SV), which include copy
      number variants (CNV), translocations, insertions, and inversions, have eluded
      easy detection and characterization, particularly in nonhuman species. However,
      evidence increasingly shows that SV not only contribute a substantial proportion
      of genetic variation but also have significant influence on phenotypes. Here we
      present the discovery of CNV in a prominent New Zealand dairy bull using long
      read PacBio (Pacific Biosciences, Menlo Park, CA) sequencing technology and the
      Sniffles SV discovery tool (version 0.0.1;
      https://github.com/fritzsedlazeck/Sniffles). The CNV identified from long reads
      were compared with CNV discovered in the same bull from Illumina sequencing using
      CNVnator (read depth-based tool; Illumina Inc., San Diego, CA) as a means of
      validation. Subsequently, further validation was undertaken using whole-genome
      Illumina sequencing of 556 cattle representing the wider New Zealand dairy cattle
      population. Very limited overlap was observed in CNV discovered from the 2
      sequencing platforms, in part because of the differences in size of CNV detected.
      Only a few CNV were therefore able to be validated using this approach. However,
      the ability to use CNVnator to genotype the 557 cattle for copy number across all
      regions identified as putative CNV allowed a genome-wide assessment of
      transmission level of copy number based on pedigree. The more highly
      transmissible a putative CNV region was observed to be, the more likely the
      distribution of copy number was multimodal across the 557 sequenced animals.
      Furthermore, visual assessment of highly transmissible CNV regions provided
      evidence supporting the presence of CNV across the sequenced animals. This
      transmission-based approach was able to confirm a subset of CNV that segregates
      in the New Zealand dairy cattle population. Genome-wide identification and
      validation of CNV is an important step toward their inclusion in genomic
      selection strategies.

PMID- 28456411
TI  - The effect of homogenization pressure on the flavor and flavor stability of whole
      milk powder.
AB  - Flavor is one of the key factors that can limit the application and shelf life of
      dried dairy ingredients. Many off-flavors are caused during ingredient
      manufacture that carry through into ingredient applications and decrease consumer
      acceptance. The objective of this research was to investigate the effect of
      homogenization pressure on the flavor and flavor stability of whole milk powder
      (WMP). Whole milk powder was produced from standardized pasteurized whole milk
      that was evaporated to 50% solids (wt/wt), homogenized in 2 stages with varying
      pressures (0/0, 5.5/1.4, 11.0/2.8, or 16.5/4.3 MPa), and spray dried. Whole milk
      powder was evaluated at 0, 3, and 6 mo of storage at 21 degrees C. Sensory
      properties were evaluated by descriptive analysis. Volatile compounds were
      analyzed by sorptive stir bar extraction with gas chromatography-mass
      spectrometry. Fat globule size in condensed whole milk and particle size of
      powders were measured by laser diffraction. Surface free fat, inner free fat, and
      encapsulated fat of WMP were measured by solvent extractions. Phospholipid
      content was measured by ultra-high-performance liquid chromatography-evaporative
      light scattering. Furosine in WMP was analyzed by ultra-high-performance liquid
      chromatography-mass spectrometry. Increased homogenization pressure decreased
      cardboard and painty flavors, volatile lipid oxidation compound concentrations,
      fat globule size in condensed milk, surface free fat, and inner free fat in WMP.
      Encapsulated fat increased and phospholipid-to-encapsulated fat ratio decreased
      with higher homogenization pressure. Surface free fat in powders increased
      cardboard flavor and lipid oxidation. These results indicate that off-flavors
      were decreased with increased homogenization pressures in WMP due to the decrease
      in free fat. To decrease off-flavor intensities in WMP, manufacturers should
      carefully evaluate these parameters during ingredient manufacture.

PMID- 28456412
TI  - Association of aqueous hydrogen concentration with methane production in
      continuous cultures modulated to vary pH and solids passage rate.
AB  - The objective of this study was to evaluate the effects of altering pH and solids
      passage rate (kp) on concentration of aqueous H2 [H2(aq)], CH4 production,
      volatile fatty acids (VFA) production, and fiber digestibility in a continuous
      culture fermentation system. The present study was conducted as a 2 * 2 factorial
      treatment arrangement in a Latin square design using continuous culture
      fermentors (n = 4). Our continuous culture system was converted to a closed
      system to measure CH4 and H2 emission while measuring H2(aq) concentration and
      VFA production for complete stoichiometric assessment of fermentation pattern.
      Treatments were control pH (CpH; ranging from 6.3 to 6.9) or low pH (LpH; 5.8 to
      6.4) factorialized with solids kp that was adjusted to be either low (Lkp;
      2.5%/h) or high (Hkp; 5.0%/h); liquid dilution was maintained at 7.0%/h.
      Fermentors were fed once daily (40 g of dry matter; 50:50 concentrate:forage
      diet). Four periods lasted 10 d each, with 3 d of sample collection. The main
      effect of LpH increased nonammonia nitrogen flow, and both LpH and Hkp increased
      nonammonia nonbacterial N flow. We observed a tendency for Hkp to increase
      bacterial N flow per unit of nonstructural carbohydrates and neutral detergent
      fiber degraded. The main effect of LpH decreased H2(aq) by 4.33 uM compared with
      CpH. The main effect of LpH decreased CH4 production rate from 5 to 9 h
      postfeeding, and Hkp decreased CH4 production rate from 3 to 9 h postfeeding. We
      found no effect of LpH on daily CH4 production or CH4 produced per gram of
      neutral detergent fiber degraded, but Hkp decreased daily CH4 production by
      33.2%. Both the main effects of LpH and Hkp decreased acetate molar percentage
      compared with CpH and Lkp, respectively. The main effect of both LpH and Hkp
      increased propionate molar percentage, decreasing acetate-to-propionate ratio
      from 2.62 to 2.34. We noted no treatment effects on butyrate molar percentage or
      total VFA production. The results indicate increasing kp and decreasing pH
      decreased acetate-to-propionate ratio, but only increasing kp decreased CH4
      production; lack of differences for LpH might be a result of compensatory
      methanogenesis during the second half of the day postfeeding.

PMID- 28456413
TI  - Deaths amenable to health care: Converging trends in the EU?
AB  - Amenable mortality has been recently included in the joint monitoring tool by the
      European Commission and Member States to assess a country's health system
      performance. Amenable deaths are premature deaths, which should not have occurred
      at this stage in the light of timely and effective health care. This paper
      recalculated annual amenable mortality rates for 28EU countries and the EU for
      the period 1994-2013 based on the recently published list of deaths amenable to
      health care by Eurostat. Thereby, it offers a consistent calculation of amenable
      mortality across European Member States and provides time series data on amenable
      mortality. In addition, a sensitivity analysis of the amenable mortality
      indicator for varying age limits and attributional weights of circulatory system
      diseases is carried out. While large improvements were made in reducing amenable
      deaths in all European countries, great variations persist among Member States.
      Most of the decreases in amenable mortality are explained by a substantial
      reduction of deaths due to circulatory system diseases. In addition, even in
      countries with good national performance on amenable mortality, sub-national
      analysis shows that great regional disparities exist. The sensitivity analysis
      revealed that for the large majority of countries results are stable across
      different attributional weights used for ischaemic heart diseases and
      cerebrovascular diseases.

PMID- 28456414
TI  - Hyperparathyroidism-induced osteosclerosis mimicking diffuse osteo-medullary
      metastases on 18F-FDG PET/CT: The role of the "rugger jersey" spine sign.

PMID- 28456415
TI  - Degradation of indoor limonene by outdoor ozone: A cascade of secondary organic
      aerosols.
AB  - In indoor air, terpene-ozone reactions can form secondary organic aerosols (SOA)
      in a transient process. 'Real world' measurements conducted in a furnished room
      without air conditioning were modelled involving the indoor background of
      airborne particulate matter, outdoor ozone infiltrated by natural ventilation,
      repeated transient limonene evaporations, and different subsequent ventilation
      regimes. For the given setup, we disentangled the development of nucleated,
      coagulated, and condensed SOA fractions in the indoor air and calculated the time
      dependence of the aerosol mass fraction (AMF) by means of a process model. The
      AMF varied significantly between 0.3 and 5.0 and was influenced by the ozone
      limonene ratio and the background particles which existed prior to SOA formation.
      Both influencing factors determine whether nucleation or adsorption processes are
      preferred; condensation is strongly intensified by particulate background. The
      results provide evidence that SOA levels in natural indoor environments can
      surpass those known from chamber measurements. An indicator for the SOA forming
      potential of limonene was found to be limona ketone. Multiplying its
      concentration (in MUg/m3) by 450(+/-100) provides an estimate of the
      concentration of the reacted limonene. This can be used to detect a high particle
      formation potential due to limonene pollution, e.g. in epidemiological studies
      considering adverse health effects of indoor air pollutants.

PMID- 28456416
TI  - The global economic burden of diabetes in adults aged 20-79 years: a cost-of
      illness study.
AB  - BACKGROUND: Differences in methods and data used in past studies have limited
      comparisons of the cost of illness of diabetes across countries. We estimate the
      full global economic burden of diabetes in adults aged 20-79 years in 2015, using
      a unified framework across all countries. Our objective was to highlight patterns
      of diabetes-associated costs as well as to identify the need for further research
      in low-income regions. METHODS: Epidemiological and economic data for 184
      countries were used to estimate the global economic burden of diabetes,
      regardless of diabetes type. Direct costs were derived using a top-down approach
      based on WHO general health expenditure figures and prevalence data from the 2015
      International Diabetes Federation Diabetes Atlas. Indirect costs were assessed
      using a human-capital approach, including diabetes-associated morbidity and
      premature mortality. FINDINGS: We estimate the global cost of diabetes for 2015
      was US$1.31 trillion (95% CI 1.28-1.36) or 1.8% (95% CI 1.8-1.9) of global gross
      domestic product (GDP). Notably, indirect costs accounted for 34.7% (95% CI 34.7
      35.0) of the total burden, although substantial variations existed both in the
      share and the composition of indirect costs across countries. North America was
      the most affected region relative to GDP and also the largest contributor to
      global absolute costs. However, on average, the economic burden as percentage of
      GDP was larger in middle-income countries than in high-income countries.
      INTERPRETATION: Our results suggest a substantial global economic burden of
      diabetes. Although limited data were available for low-income and middle-income
      countries, our findings suggest that large diabetes-associated costs are not only
      a problem in high-income settings but also affect poorer world regions. FUNDING:
      None.

PMID- 28456417
TI  - Global economic burden of diabetes and its implications.

PMID- 28456418
TI  - Transmitting Trauma: A systematic review of vicarious racism and child health.
AB  - Racism is a pervasive stressor. Although most research focuses on direct targets,
      racism can also have unintended victims. Because children's lives are inevitably
      linked to the experiences of other individuals, and they are in critical phases
      of development, they are especially vulnerable to such stressors. Despite the
      growing body of literature on children's direct exposure to racism, little is
      known about the relationship between vicarious racism (i.e. secondhand exposure
      to racism) and child health. To examine the state of this literature, we
      performed a systematic review and screened 1371 articles drawn from 7 databases,
      with 30 studies meeting inclusion criteria. For these 30, we reviewed research
      methodology, including conceptualization and measurement of vicarious exposure,
      sample characteristics, significant associations with child health outcomes, and
      mediators and/or moderators of those associations. Most studies were published
      after 2011 in urban areas in the U.S., employed longitudinal designs, and focused
      on African American populations. Socioemotional and mental health outcomes were
      most commonly reported with statistically significant associations with vicarious
      racism. While all studies examined racism indirectly experienced by children,
      there was no standard definition of vicarious racism used. We organize the
      findings in a schematic diagram illustrating indirectly-experienced racism and
      child health outcomes to identify current gaps in the literature and ways in
      which to bridge those gaps. To further the field, vicarious racism should be
      uniformly defined and directly measured using psychometrically validated tools.
      Future studies should consider using children as the informants and follow
      children into early adulthood to better understand causal mechanisms. Given the
      recent national exposure to racially-charged events, a deeper understanding of
      the association between vicarious racism and child health is crucial in fueling
      research-informed social action to help children, families, and communities
      exposed to racism. PROSPERO registration number: CRD42016039608.

PMID- 28456419
TI  - Choroidal Imaging with Swept-Source Optical Coherence Tomography in Patients with
      Birdshot Chorioretinopathy: Choroidal Reflectivity and Thickness.
AB  - PURPOSE: To characterize choroidal thickness and choroidal reflectivity in the
      eyes of patients with birdshot chorioretinopathy (BSCR). DESIGN: Cross-sectional
      observational study. PARTICIPANTS: Two hundred twenty BSCR patients and 59
      healthy controls. METHODS: Patients with BSCR and healthy controls underwent
      imaging of the macula in both eyes with a swept-source optical coherence
      tomography device (DRI-OCT1 Atlantis; Topcon). Images were exported from the
      device, and analysis was performed by 2 graders in the Doheny Image Reading
      Center using Image J software. The choroidal thickness at the foveal center was
      measured. In addition, the inner and outer boundaries of the choroid and retinal
      pigment epithelium (RPE) as well as the inner retinal surface all were segmented
      to allow the brightness and reflectivity of the pixels in the choroid, RPE band,
      and overlying vitreous to be quantified. An adjusted or normalized choroidal
      reflectivity, with the RPE as the bright reference standard and the vitreous as
      the dark reference standard, was computed using the formula: normalized choroidal
      reflectivity = (choroidal reflectivity-vitreous reflectivity)/RPE reflectivity.
      MAIN OUTCOME MEASURES: Choroidal reflectivity and choroidal thickness. RESULTS:
      Three hundred eighty-six eyes in the BSCR group and 59 eyes in the control group
      were included in this analysis. Higher choroidal reflectivity and lower choroidal
      thickness were documented in inactive BSCR patients compared with active BSCR and
      controls (P < 0.01). Active BSCR patients showed lower choroidal thickness
      compared with controls (P < 0.01). There was a negative correlation between
      choroidal reflectivity and choroidal thickness (r = -0.793; P < 0.001). On
      multiple regression analysis, choroidal thickness, age, and disease duration (all
      P < 0.01) all were significant predictors of choroidal reflectivity. CONCLUSIONS:
      Choroidal reflectivity and choroidal thickness changes are evident in active and
      inactive BSCR patients. Novel choroidal parameters such as choroidal reflectivity
      may warrant further study in the setting of BSCR.

PMID- 28456420
TI  - The Evolution of Outer Retinal Tubulation, a Neurodegeneration and Gliosis
      Prominent in Macular Diseases.
AB  - PURPOSE: To document outer retinal tubulation (ORT) formation in advanced retinal
      disorders. DESIGN: Retrospective, observational study. PARTICIPANTS: Consecutive
      cases with retinal diseases showing outer retinal disruption and atrophy of the
      retinal pigment epithelium (RPE) associated with ORT on spectral-domain (SD)
      optical coherence tomography (OCT) at the final available visit. METHODS: Cross
      sectional SD OCT scans showing ORT at the last available visit were compared with
      eye-tracked baseline scans. Only patients showing the formation of ORT over time
      with absence of ORT at baseline were analyzed. MAIN OUTCOME MEASURES: Steps in
      ORT formation based on shapes of the external limiting membrane (ELM) descent
      (flat, curved, reflected, and scrolled) at the border of outer retinal and RPE
      atrophy, ORT characteristics (open, closed), and time between steps through a
      long-term follow-up. RESULTS: From 170 eyes of 86 patients with ORT, 38 eyes of
      30 patients (11 men, 19 women) with a mean age of 78.87 years (range, 56-96
      years) met inclusion criteria. Of these 38 eyes, 23 (60%) had geographic atrophy
      secondary to age-related macular degeneration (AMD) and 2 eyes (5%) had
      geographic atrophy secondary to pattern dystrophy. Twelve eyes (32%) had
      neovascular AMD and 1 eye (3%) had neovascularization secondary to pseudoxanthoma
      elasticum, all showing similar ORT formative steps. Seventy-three different
      retinal areas (1434 cross-sectional images) were analyzed over a mean follow-up
      of 69.5 months (range, 21-93 months). At 73 borders, grading of eye-tracked
      follow-up SD OCT line scans showed a flat ELM descent at least once at 34 borders
      (47%), a curved ELM at 47 borders (64%), a reflected ELM at 37 borders (51%), and
      a scrolled ELM at 24 borders (33%). Of 81 ORTs, 73 (90%) were closed and 8 (10%)
      were open. The mean time for ORT formation was 14.9 months (range, 1.4-71.3
      months). CONCLUSIONS: We propose progressive steps in the development of ORT and
      analyze the time of progression between these steps. Analyzing the borders of
      atrophy to determine the origin of ORT provides new insights into the
      pathophysiology of advanced retinal disease highlighting a role for Muller cells
      and may inform future therapeutic strategies.

PMID- 28456422
TI  - Validation of the Danish version of the constipation risk assessment scale
      (CRAS).
AB  - INTRODUCTION: The Constipation Assessment Scale (CRAS) was developed in order to
      enable the prediction of the risk of developing constipation. The scale needs
      validation in acute and elective patients with common disorders. MATERIALS AND
      METHOD: Two hundred and six acute patients with hip fracture and 200 elective
      patients with total knee or hip replacement were included. They were assessed
      with CRAS before surgery and their defecation pattern, stool consistency and
      degree of straining were measured at admission and 30 days after surgery.
      RESULTS: The prevalence of constipation was 0.49 for the acute patients and 0.34
      for the elective patients. Sensitivity was 0.67 and 0.57. Specificity was 0.54
      and 0.52. Positive predictive value was 0.59 and 0.38, whereas the negative
      predictive value was 0.63 and 0.7. CONCLUSION: When used in an orthopaedic ward,
      the prognostic accuracy of CRAS is poor and it cannot be recommended as a
      screening tool.

PMID- 28456421
TI  - Mendelian Randomization Implicates High-Density Lipoprotein Cholesterol
      Associated Mechanisms in Etiology of Age-Related Macular Degeneration.
AB  - PURPOSE: Undertake a systematic investigation into associations between genetic
      predictors of lipid fractions and age-related macular degeneration (AMD) risk.
      DESIGN: Two-sample Mendelian randomization investigation using published data.
      PARTICIPANTS: A total of 33 526 individuals (16 144 cases, 17 832 controls)
      predominantly of European ancestry from the International Age-related Macular
      Degeneration Genomics Consortium. METHODS: We consider 185 variants previously
      demonstrated to be associated with at least 1 of low-density lipoprotein (LDL)
      cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides at a
      genome-wide level of significance, and test their associations with AMD. We
      particularly focus on variants in gene regions that are proxies for specific
      pharmacologic agents for lipid therapy. We then conduct a 2-sample Mendelian
      randomization investigation to assess the causal roles of LDL-cholesterol, HDL
      cholesterol, and triglycerides on AMD risk. We also conduct parallel
      investigations for coronary artery disease (CAD) (viewed as a positive control)
      and Alzheimer's disease (a negative control) for comparison. MAIN OUTCOME
      MEASURES: Diagnosis of AMD. RESULTS: We find evidence that HDL-cholesterol is a
      causal risk factor for AMD, with an odds ratio (OR) estimate of 1.22 (95%
      confidence interval [CI], 1.03-1.44) per 1 standard deviation increase in HDL
      cholesterol. No causal effect of LDL-cholesterol or triglycerides was found.
      Variants in the CETP gene region associated with increased circulating HDL
      cholesterol also associate with increased AMD risk, although variants in the LIPC
      gene region that increase circulating HDL-cholesterol have the opposite direction
      of association with AMD risk. Parallel analyses suggest that lipids have a
      greater role for AMD compared with Alzheimer's disease, but a lesser role than
      for CAD. CONCLUSIONS: Some genetic evidence suggests that HDL-cholesterol is a
      causal risk factor for AMD risk and that increasing HDL-cholesterol (particularly
      via CETP inhibition) will increase AMD risk.

PMID- 28456424
TI  - Surgical anomalies in twins: The role of assisted reproductive technology and
      chorionicity: RE: "Congenital malformations associated with assisted reproductive
      technology: A California statewide analysis" by Kelley-Quon LI et al. J Pediatr
      Surg 2013; 48; 1218-1224.

PMID- 28456423
TI  - Staphylococcus aureus Promotes Smed-PGRP-2/Smed-setd8-1 Methyltransferase
      Signalling in Planarian Neoblasts to Sensitize Anti-bacterial Gene Responses
      During Re-infection.
AB  - Little is known about how organisms exposed to recurrent infections adapt their
      innate immune responses. Here, we report that planarians display a form of
      instructed immunity to primo-infection by Staphylococcus aureus that consists of
      a transient state of heightened resistance to re-infection that persists for
      approximately 30days after primo-infection. We established the involvement of
      stem cell-like neoblasts in this instructed immunity using the complementary
      approaches of RNA-interference-mediated cell depletion and tissue grafting
      mediated gain of function. Mechanistically, primo-infection leads to expression
      of the peptidoglycan receptor Smed-PGRP-2, which in turn promotes Smed-setd8-1
      histone methyltransferase expression and increases levels of lysine methylation
      in neoblasts. Depletion of neoblasts did not affect S. aureus clearance in primo
      infection but, in re-infection, abrogated the heightened elimination of bacteria
      and reduced Smed-PGRP-2 and Smed-setd8-1 expression. Smed-PGRP-2 and Smed-setd8-1
      sensitize animals to heightened expression of Smed-p38 MAPK and Smed-morn2, which
      are downstream components of anti-bacterial responses. Our study reveals a
      central role of neoblasts in innate immunity against S. aureus to establish a
      resistance state facilitating Smed-sted8-1-dependent expression of anti-bacterial
      genes during re-infection.

PMID- 28456425
TI  - The position of a written document in preoperative information for pediatric
      surgery: A randomized controlled trial on parental anxiety, knowledge, and
      satisfaction.
AB  - INTRODUCTION: Preoperative information is a legal and ethical obligation. Very
      little studies have evaluated the preoperative information method in pediatrics.
      Having a child operated on is stressful for the parents. Improving information is
      a way to lower their anxiety. Our study aims to measure the impact of a leaflet,
      which supports spoken information on parental anxiety, the comprehension
      memorization of the information and their satisfaction. MATERIALS & METHODS:
      Prospective study including 178 patients of outpatient surgery, randomized in two
      groups: spoken information versus spoken information supported by a leaflet,
      which is then handed out to the parents. The messages were identical:
      physiopathology, risks without treatment, surgical technique and its possible
      complications, description of the hospitalization day, and postoperative care.
      Parental evaluation was made with self-questionnaires after the preoperative
      consultation, then on the day of surgery. At each moment we evaluated the level
      of anxiety, satisfaction of information quality and the comprehension
      memorization of the data. RESULTS: Written information significantly improves the
      scores of comprehension-memorization, parental satisfaction and significantly
      decreases the level of anxiety. CONCLUSION: Significant impact of the written
      document as communication support in pediatric surgery, validating the method and
      encouraging it to be generalized to other pediatric surgery acts. LEVEL OF
      EVIDENCE: Level I. TYPE OF STUDY: Prognosis study.

PMID- 28456426
TI  - Comparing groups with an effect size and confidence intervals approach: A
      reminder.

PMID- 28456427
TI  - [How to make your own custom cutting guides for both mandibular and fibular stair
      step osteotomies?]
AB  - INTRODUCTION: Using tailored cutting guides for osteocutaneous free fibula flap
      in complex mandibular reconstruction after cancer resection surgery constitutes a
      substantial improvement. Autonomously conceiving and manufacturing the cutting
      guides within a plastic surgery department with computer-aided design (CAD) and
      three-dimensional (3D) printing allows planning more complex osteotomies, such as
      stair-step osteotomies, in order to achieve more stable internal fixations.
      METHODS: For the past three years, we have been producing by ourselves patient
      tailored cutting guides using CAD and 3D printing. Osteotomies were virtually
      planned, making the cutting lines more complex in order to optimize the internal
      fixation stability. We also printed reconstructed mandible templates and shaped
      the reconstruction plates on them. We recorded data including manufacturing
      techniques and surgical outcomes. RESULTS: Eleven consecutive patients were
      operated on for an oral cavity cancer. For each patient, we planned the fibular
      and mandibular stair-step osteotomies and we produced tailored cutting guides. In
      all patients, we achieved to get immediately stable internal fixations and in 10
      patients, a complete bone consolidation after 6 months. CONCLUSION: Autonomously
      manufacturing surgical cutting guides for mandibular reconstruction by free
      fibula flap is a significant improvement, regarding ergonomics and precision.
      Planning stair-step osteotomies to perform complementary internal fixation
      increases contact surface and congruence between the bone segments, thus
      improving the reconstructed mandible stability.

PMID- 28456428
TI  - [Phalloplasty: Microsurgical options and management algorithm].
AB  - The free radial forearm flap is considered as the gold standard in penile
      reconstruction for good functional and aesthetic results. The scar on donor site
      could be considered as pathognomonic of their situation by transsexual patients.
      The development of microsurgical flaps provides new therapeutic options. This
      options are discussed and a therapeutic algorithm is presented. The main
      techniques used are the pedicled anterolateral thigh perforator flap and free
      muscle sparing latissimus dorsi flap. Principal criteria are listed, the choice
      of patient and the local anatomical conditions are the most important.
      Antebrachial flap stay the first choice. In case of non-feasibility of this flap,
      phalloplasty with pedicle ALT flap or free MSLD flap will be proposed. Urethral
      reconstruction will be done by a narrow free forearm flap or by a delayed thin
      skin graft or buccal mucosa graft. Microsurgical phalloplasty options are not
      limited to the forearm flap. Satisfactory results can be obtained using
      alternative procedure. The use of a therapeutic algorithm allows to choose the
      most optimal solution for each patient.

PMID- 28456433
TI  - ?

PMID- 28456429
TI  - [Superficial Circumflex Iliac Artery Perforator flap (SCIP flap): Revival of the
      inguinal donor site?]
AB  - The SCIP flap based on a superficial circumflex iliac perforator artery (SCIA)
      was described for the first time by Koshima in 2004 as a large and thin groin
      flap, with a low morbidity. The purpose of this study is to demonstrate the
      benefits of SCIP flap to cover cutaneous defects. We present a retrospective
      study from January 2007 to August 2016. Twelve patients had a SCIP flap
      reconstruction in the plastic surgery department of Amiens hospital. Thirteen
      flaps were performed. The average preoperative doppler mapping time was 8minutes.
      The average size of flaps was 62.5cm2 [21; 180cm2]. The average time required for
      raising flaps was 61min [52; 82min]. It has not been observed any complication of
      the flap or donor site. The SCIP flap has a thin paddle and the donor site
      morbidity is minimal. The surgical technique is safe, accessible and precision is
      increased by preoperative color doppler mapping. The many strengths of the SCIP
      flap make it a must in the algorithm for defects management and come to
      revitalize the inguinal donor site.

PMID- 28456435
TI  - Apparent Heterotopic Pregnancy Created by Mirror Image Artifact.

PMID- 28456430
TI  - Comparison of four PCR methods for efficient detection of Trypanosoma cruzi in
      routine diagnostics.
AB  - Due to increased migration, Chagas disease has become an international health
      problem. Reliable diagnosis of chronically infected people is crucial for
      prevention of non-vectorial transmission as well as treatment. This study
      compared four distinct PCR methods for detection of Trypanosoma cruzi DNA for the
      use in well-equipped routine diagnostic laboratories. DNA was extracted of T.
      cruzi-positive and negative patients' blood samples and cultured T. cruzi, T.
      rangeli as well as Leishmania spp. One conventional and two real-time PCR methods
      targeting a repetitive Sat-DNA sequence as well as one conventional PCR method
      targeting the variable region of the kDNA minicircle were compared for
      sensitivity, intra- and interassay precision, limit of detection, specificity and
      cross-reactivity. Considering the performance, costs and ease of use, an
      algorithm for PCR-diagnosis of patients with a positive serology for T. cruzi
      antibodies was developed.

PMID- 28456434
TI  - Recurrent Massive Perivillous Fibrin Deposition and Chronic Intervillositis
      Treated With Heparin and Intravenous Immunoglobulin: A Case Report.
AB  - BACKGROUND: Massive perivillous fibrin deposition (MPVFD) and chronic
      intervillositis (CI) are related rare pathological correlates of severe
      intrauterine growth restriction (IUGR) and fetal loss with high recurrence rates.
      No standard management has been established. CASE: A patient underwent
      termination of pregnancy at 21 weeks for severe early onset IUGR. Placental
      histology showed mixed CI with MPVFD. Several months later, the patient became
      pregnant and was managed with prednisone and aspirin (ASA) but miscarried at 16
      weeks. Placental pathology showed MPVFD and focal CI. For two subsequent
      pregnancies, she was treated with intravenous immunoglobulin (IVIG), heparin, and
      ASA. Both pregnancies resulted in healthy near-term deliveries with normal
      placentas. CONCLUSION: IVIG, heparin, and ASA can be an option in patients with
      recurrent pregnancy loss due to MPVFD and CI.

PMID- 28456432
TI  - Maternal immune correlates of protection against placental transmission of
      cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen
      worldwide, impacting an estimated 1 million newborns annually. In a subset of
      infected infants, congenital HCMV causes severe, long-lasting sequelae, including
      deafness, microcephaly, neurodevelopmental delay, and even death. Accordingly, a
      maternal vaccine to prevent congenital HCMV infection continues to be a top
      public health priority. Nevertheless, all vaccines tested to date have failed to
      meet clinical trial endpoints. Maternal immunity provides partial protection
      against congenital HCMV transmission, as vertical transmission from seropositive
      mothers is relatively rare. Therefore, an understanding of the maternal immune
      correlates of protection against HCMV congenital infection will be critical to
      inform design of an efficacious maternal vaccine. This review summarizes our
      understanding of the innate and adaptive immune correlates of protection against
      congenital transmission of HCMV, and discusses the advantages and applications of
      a novel nonhuman primate model of congenital CMV transmission to aid in rational
      vaccine design and evaluation.

PMID- 28456436
TI  - Centrally located GLP-1 receptors modulate gastric slow waves and cardiovascular
      function in ferrets consistent with the induction of nausea.
AB  - Glucagon-like peptide-1 (GLP-1) receptor agonists are indicated for the treatment
      of Type 2 diabetes and obesity, but can cause nausea and emesis in some patients.
      GLP-1 receptors are distributed widely in the brain, where they contribute to
      mechanisms of emesis, reduced appetite and aversion, but it is not known if these
      centrally located receptors also contribute to a modulation of gastric slow wave
      activity, which is linked causally to nausea. Our aim was to investigate the
      potential of the GLP-1 receptor agonist, exendin-4, administered into the 3rd
      ventricle to modulate emesis, feeding and gastric slow wave activity.
      Thermoregulation and cardiovascular parameters were also monitored, as they are
      disturbed during nausea. Ferrets were used as common laboratory rodents do not
      have an emetic reflex. A guide cannula was implanted into the 3rd ventricle for
      delivering a previously established dose of exendin-4 (10nmol), which had been
      shown to induce emesis and behaviours indicative of 'nausea'. Radiotelemetry
      recorded gastric myoelectric activity (GMA; slow waves), blood pressure and heart
      rate variability (HRV), and core temperature; food intake and behaviour were also
      assessed. Exendin-4 (10nmol, i.c.v.) decreased the dominant frequency of GMA,
      with an associated increase in the percentage of bradygastric power (lasting
      ~4h). Food intake was inhibited in all animals, with 63% exhibiting emesis.
      Exendin-4 also increased blood pressure (lasting ~24h) and heart rate (lasting
      ~7h), decreased HRV (lasting ~24h), and caused transient hyperthermia. None of
      the above parameters were emesis-dependent. The present study shows for the first
      time that gastric slow waves may be modulated by GLP-1 receptors in the brain
      through mechanisms that appear independent from emesis. Taken together with a
      reduction in HRV, the findings are consistent with changes associated with the
      occurrence of nausea in humans.

PMID- 28456431
TI  - IFPA meeting 2016 workshop report III: Decidua-trophoblast interactions;
      trophoblast implantation and invasion; immunology at the maternal-fetal
      interface; placental inflammation.
AB  - Workshops are an important part of the IFPA annual meeting as they allow for
      discussion of specialised topics. At IFPA meeting 2016 there were twelve themed
      workshops, four of which are summarized in this report. These workshops related
      to various aspects of placental biology but collectively covered areas of
      decidual-trophoblast interaction, regulation of trophoblast invasion, immune
      cells at the maternal-fetal interface, and placental inflammation.

PMID- 28456437
TI  - Spinal neuropeptide modulation, functional assessment and cartilage lesions in a
      monosodium iodoacetate rat model of osteoarthritis.
AB  - BACKGROUND AND AIMS: Characterising the temporal evolution of changes observed in
      pain functional assessment, spinal neuropeptides and cartilage lesions of the
      joint after chemical osteoarthritis (OA) induction in rats. METHODS AND RESULTS:
      On day (D) 0, OA was induced by an IA injection of monosodium iodoacetate (MIA).
      Rats receiving 2mg MIA were temporally assessed at D3, D7, D14 and D21 for the
      total spinal cord concentration of substance P (SP), calcitonin gene related
      peptide (CGRP), bradykinin (BK) and somatostatin (STT), and for severity of
      cartilage lesions. At D21, the same outcomes were compared with the IA 1mg MIA,
      IA 2mg MIA associated with punctual IA injection of lidocaine at D7, D14 and D21,
      sham (sterile saline) and naive groups. Tactile allodynia was sequentially
      assessed using a von Frey anaesthesiometer. Non-parametric and mixed models were
      applied for statistical analysis. Tactile allodynia developed in the 2mg MIA
      group as soon as D3 and was maintained up to D21. Punctual IA treatment with
      lidocaine counteracted it at D7 and D14. Compared to naive, [STT], [BK] and
      [CGRP] reached a maximum as early as D7, which plateaued up to D21. For [SP], the
      increase was delayed up to D14 and maintained at D21. No difference in levels of
      neuropeptides was observed between MIA doses, except for higher [STT] in the 2mg
      MIA group (P=0.029). Neuropeptides SP and BK were responsive to lidocaine
      treatment. The increase in severity of cartilage lesions was significant only in
      the 2mg MIA groups (P=0.01). CONCLUSION: In the MIA OA pain model, neuropeptide
      modulation appears early, and confirms the central nervous system to be an
      attractive target for OA pain quantification. The relationship of neuropeptide
      release with severity of cartilage lesions and functional assessment are
      promising and need further validation.

PMID- 28456439
TI  - Updating the Update: The Final Word on Milrinone and Mortality After Cardiac
      Surgery?

PMID- 28456440
TI  - The Renal Frontier in TAVR.

PMID- 28456438
TI  - Accumulated exposure to unemployment is related to impaired glucose metabolism in
      middle-aged men: A follow-up of the Northern Finland Birth Cohort 1966.
AB  - AIMS: We explored whether registered unemployment is associated with impaired
      glucose metabolism in general population. METHODS: Based on Northern Finland
      Birth Cohort 1966 at 46 years, we analyzed the oral glucose tolerance tests of
      1970 men and 2544 women in relation to their preceding three-year employment
      records in three categories of unemployment exposure: no (employed), low (<=1
      year) and high exposure (>1-year). RESULTS: Among men, pre-diabetes was found in
      19.2% of those with no unemployment, 23.0% with low and 27.0% with high exposure,
      the corresponding figures for screen-detected type 2 diabetes were 3.8%, 3.8% and
      9.2% (p<0.01). Among women, analogous figures for pre-diabetes were 10.0%, 12.6%
      and 16.2% and for screen-detected type 2 diabetes 1.7%, 3.4% and 3.6% (p<0.01).
      Men with high exposure to unemployment had a higher risk for pre-diabetes (OR
      1.61, CI 95% 1.03-2.51) and screen-detected type 2 diabetes (OR 2.58 95% CI 1.23
      5.44) than employed men, after adjustment for education, smoking, alcohol intake,
      physical activity and body mass index. Among women, associations were attenuated
      in the adjusted models. CONCLUSIONS: High exposure to unemployment may predispose
      to type 2 diabetes in middle-aged men. For clinicians, awareness of the patient's
      unemployment status may be helpful in recognizing undiagnosed cases.

PMID- 28456441
TI  - Surgical treatment and management of the severely burn patient: Review and
      update.
AB  - Since one of the main challenges in treating acute burn injuries is preventing
      infection, early excising of the eschar and covering of the wound becomes
      critical. Non-viable tissue is removed by initial aggressive surgical
      debridement. Many surgical options for covering the wound bed have been
      described, although split-thickness skin grafts remain the standard for the rapid
      and permanent closure of full-thickness burns. Significant advances made in the
      past decades have greatly improved burns patient care, as such that major future
      improvements in survival rates seem to be more difficult. Research into stem
      cells, grafting, biomarkers, inflammation control, and rehabilitation will
      continue to improve individualized care and create new treatment options for
      these patients.

PMID- 28456442
TI  - Preliminary investigation of preoperative pregabalin and total intravenous
      anesthesia doses: a randomized controlled trial.
AB  - STUDY OBJECTIVE: To determine the efficacy of 2 different doses (150-300mg) of
      preoperative pregabalin on propofol and remifentanil doses for total intravenous
      anesthesia in laparoscopic cholecystectomy. DESIGN: Prospective, randomized,
      placebo-controlled, double-blinded study. SETTING: Training and research
      hospital. PATIENTS: Forty-eight adult, American Society of Anesthesiologists
      physical status 1 and 2 patients. INTERVENTIONS: Patients were randomly assigned
      to 3 groups to receive orally 1hour before surgery, a placebo group (group 1),
      pregabalin 150mg (group 2), or pregabalin 300mg (group 3). MEASUREMENTS: In the
      operating room, heart rate, systolic and diastolic blood pressures, SpO2,
      bispectral index, and body temperature were recorded just before anesthesia
      induction; 1 and 5minutes after induction; and at minutes 10, 15, 20, 25, 30, 35,
      and 40 of the surgery. Required propofol and remifentanil doses to obtain
      bispectral index value less than 60 were also recorded. MAIN RESULTS: The
      remifentanil doses used in the pregabalin groups at minutes 10, 15, 20, 25, and
      30 and propofol doses at minutes 15, 20, 25, and 30 were statistically
      significantly lower in comparison to the placebo group. CONCLUSION: The
      observations provide preliminary evidence that preoperative pregabalin may
      decrease anesthetic agent requirement in total intravenous anesthesia patients.

PMID- 28456443
TI  - Salvage hepatectomy for local recurrence of hepatocellular carcinomas offers
      survival comparable to that of matched patients who undergo primary
      hepatectomies.
AB  - BACKGROUND: The feasibility of salvage hepatectomy for locally recurrent
      hepatocellular carcinomas (HCCs) is unclear, especially for patients with viable
      parts of previously multinodular tumors. METHODS: We reviewed charts of patients
      who underwent initial hepatectomies between 2000 and 2014 to select those with
      local recurrences (LR) after non-surgical treatments. Their postoperative
      outcomes, including morbidity, recurrence-free survival (RFS), and overall
      survival (OS) were compared with matched patients who underwent initial
      hepatectomies for primary HCCs (PR). Their local recurrence patterns were divided
      into recurrent solitary tumors (Subgroup A); and recurrent parts of multinodular
      tumors (Subgroup B). RESULTS: Among 664 patients, hepatectomy for LR was
      performed in 62 patients. Matched 59 patients were selected as PR.
      Clinicopathologic profiles at initial surgery were comparable between the LR and
      PR groups. Incidence of major morbidity (LR vs. PR, 7% vs. 5%, P = 1.00), 5-year
      RFS (21% vs. 37%, P = 0.28), and 5-year OS (69% vs. 69%, P = 0.62) were
      comparable. In the LR group, Subgroup B showed worse 5-year RFS (A vs. B, 29% vs.
      0%, P < 0.01) and 5-year-OS (80% vs. 53%, P = 0.01). Postoperative recurrence
      occurred in 46 patients, but local and extrahepatic recurrence was seen only in 2
      patients and 2 patients, respectively. CONCLUSION: Salvage hepatectomy for
      locally recurrent HCCs is feasible, and results in prognosis comparable with
      hepatectomy for primary HCCs. Although the risk of postoperative recurrence was
      high in Subgroup B, rare local recurrence suggests the usefulness of salvaging
      uncontrolled tumor by nonsurgical treatment.

PMID- 28456444
TI  - Creation of a bovine herpes virus 1 (BoHV-1) quantitative particle standard by
      transmission electron microscopy and comparison with established standards for
      use in real-time PCR.
AB  - Standards are pivotal for pathogen quantification by real-time PCR (qPCR);
      however, the creation of a complete and universally applicable virus particle
      standard is challenging. In the present study a procedure based on purification
      of bovine herpes virus type 1 (BoHV-1) and subsequent quantification by
      transmission electron microscopy (TEM) is described. Accompanying quantitative
      quality controls of the TEM preparation procedure using qPCR yielded recovery
      rates of more than 95% of the BoHV-1 virus particles on the grid used for virus
      counting, which was attributed to pre-treatment of the grid with 5% bovine
      albumin. To compare the value of the new virus particle standard for use in qPCR,
      virus counter based quantification and established pure DNA standards represented
      by a plasmid and an oligonucleotide were included. It could be shown that the
      numbers of virus particles, plasmid and oligonucleotide equivalents were within
      one log10 range determined on the basis of standard curves indicating that
      different approaches provide comparable quantitative values. However, only virus
      particles represent a complete, universally applicable quantitative virus
      standard that meets the high requirements of an RNA and DNA virus gold standard.
      In contrast, standards based on pure DNA have to be considered as sub-standard
      due to limited applications.

PMID- 28456445
TI  - "Invasive Helicobacter pylori" should be defined by combination of virulence
      genes with colonization features.

PMID- 28456446
TI  - Potential mechanisms behind the antioxidant actions of prolactin in the retina.
AB  - Causes for age-related retinal diseases are numerous and complex, and they are
      intertwined with the natural vision decline that accompanies aging. The
      elucidation of endogenous mechanisms that help maintain retinal function under
      conditions that are threatening for the eye and happen during natural aging is
      therefore critical in developing new prevention and therapeutic strategies
      against age-related retinal degeneration. Our lab recently reported that the
      hormone of lactation, prolactin, helps the retinal pigment epithelium to survive
      via antioxidant actions that result in the inhibition of sirtuin2-dependent cell
      death (EbioMedicine issue of May). The mechanism behind the antioxidant activity
      of prolactin remains elusive. The main purposes of my commentary are to discuss
      mechanisms that could explain this effect in the context of previously identified
      defense mechanisms against oxidative stress and focus particularly on the
      potential regulation of reduced glutathione levels by prolactin. I also briefly
      comment on how our study contributes to cell biology, which as the foundational
      science for understanding neurodegeneration, may accelerate progress in disease
      prevention and cures.

PMID- 28456447
TI  - Antithymocyte globulins in renal transplantation-from lymphocyte depletion to
      lymphocyte activation: The doubled-edged sword.
AB  - Compelling data suggest that lymphocyte depletion following T cell depleting
      therapy may induce prolonged CD4 T cell lymphopenia and trigger lymphocyte
      activation in some patients. These profound and non-reversible immune changes in
      T cell pool subsets are the consequence of both impaired thymic renewal and
      peripheral homeostatic proliferation. Chronic viral challenges by CMV play a
      major role in these immune alterations. Even when the consequences of CD4 T cell
      lymphopenia have been now well described, recent studies shed new light on the
      clinical consequences of immune activation. In this review, we will first focus
      on the mechanisms involved in T cell pool reconstitution after T cell depletion
      and further consider the clinical consequences of ATG-induced T cell activation
      and senescence in renal transplant recipients.

PMID- 28456448
TI  - Prospective, longitudinal assessment of quality of life in patients with cancer
      of the head and neck and their primary carers.
AB  - Cancer of the head and neck has profound psychosocial and physical effects on
      patients, so quality of life (QoL) is an essential consideration-not only is it
      of importance to the patient but it also provides a subjective measure of the
      success of treatment. However, we know of little work about its influence on
      carers. The aim of this study was to assess the impact of the diagnosis and
      treatment on the QoL of patients and their carers from baseline (preoperatively)
      to three months postoperatively. Thirty-six patients and 21 primary carers were
      enrolled, and patients completed one head-and-neck-specific measure, the
      University of Washington Head and Neck, Version Four (UW-V4), and three other
      questionnaires, both at the time of diagnosis and at one and three months
      postoperatively. The carers completed similar questionnaires except for the UW
      V4. Analysis of the patients' data showed a serious deterioration in psychosocial
      and physical domains at one month postoperatively. However, the analysis of
      carers' data showed a highly significant deterioration in anxiety and depression
      domains (p<0.01), which remained low after three months. These findings highlight
      the need for psychological support not only for patients but also for their
      primary carers during the management of carcinoma of the head and neck.

PMID- 28456449
TI  - Incidence of salivary side effects after radioiodine treatment using a new
      specifically-designed questionnaire.
AB  - Sialadenitis is one of the common complications of radioiodine treatment for
      thyroid malignancy. The aim of this study was to evaluate the prevalence of
      radioiodine-induced sialadenitis and other side effects by using a self
      administered questionnaire. From 1 January 2011 to 31 December 2012 all
      consecutive patients with a newly-established diagnosis of thyroid cancer who
      were treated with adjuvant radioiodine at La Timone University Hospital were sent
      a self-administered questionnaire on salivary complaints that had been
      specifically designed for this study. A total of 413 patients sent the
      questionnaire back, of whom 100 (24%) had experienced pain, 116 (28%) discomfort
      or swelling, and 147 (36%) dry mouth or xerostomia. This survey has highlighted
      the number of side effects of radioiodine treatment in a large group of patients
      and corroborates previous observations. Our new self-administered questionnaire
      may be useful to others for follow-up and research.

PMID- 28456450
TI  - Modification of orbital retractor to facilitate the insertion of orbital wall
      implants.

PMID- 28456451
TI  - High-sensitivity determination of estrogens in fish plasma using chemical
      derivatization upstream UHPLC-MSMS.
AB  - This article describes the development and validation of a sensitive LC-MSMS
      method for determination of estrogen in fish plasma. Dansyl chloride
      derivatization of the phenol functional group in estrogen was used to enhance the
      response to atmospheric pressure ionization leading to improve the sensitivity.
      Individual 13C internal standards were selected after comparison with deuterated
      standards. Liquid-liquid extraction (ethyl acetate or methyl tert-butyl ether)
      and protein precipitation (acetonitrile, methanol or acetone) were compared for
      the extraction and clean-up of estrogens from fish plasma. Ethyl acetate was
      selected as the best alternative with recovery ranging from 61 to 96% and matrix
      effect ranging from 88 to 106%. Limits of quantification ranged from 0.5 to
      1pg/mL showing a gain in sensitivity of 10,000 times over electrospray ionization
      of underivatized estrogens. Accuracy and precision were validated over three
      consecutive days and the method was applied to measure estrogen in sea lamprey
      (Petromyzon marinus) and lake trout (Salvelinus namaycush) plasma. Estrone and
      estriol were detected in fish below 1ng/mL in plasma, justifying the need of a
      highly sensitive LC-MSMS quantification method.

PMID- 28456452
TI  - Oral mass revealing Chediak-Higashi syndrome.
AB  - This case report describes common oral inflammatory findings leading to the
      identification of Chediak-Higashi syndrome (CHS). A 15-year-old girl presented
      with an enlarging and painful mass on the upper lip. Two weeks after the initial
      visit, the mass showed further protrusion in the absence of fever. Magnetic
      resonance imaging revealed a well-circumscribed cystic lesion with a thick
      capsule, and suggested an abscess derived from the mucous cyst in the upper lip.
      Inflammation indices were not elevated; however neutrophils were significantly
      lower than the normal level. Giant cytoplasmic granules in neutrophils,
      eosinophils, and lymphocytes, which are pathognomonic of CHS, were noted. The
      patient displayed brownish-red hair with some grey hair, and partial
      oculocutaneous albinism. Hepatosplenomegaly was evident on ultrasonography. The
      final diagnosis was of an oral infection facilitated by the adolescent form of
      CHS (gene CHS1/LYST at 1q42.1-2). This report offers a reminder that lip swelling
      may represent the initial manifestation of the inflammatory response in a patient
      with loss of immunocompetence due to pathologies such as CHS, and may rarely
      present as the patient's main complaint.

PMID- 28456454
TI  - Metabolic flux network analysis of hydrogen production from crude glycerol by
      Clostridium pasteurianum.
AB  - The present study has attempted to get insight into ultrasound induced
      enhancement in biohydrogen production from glycerol fermentation using metabolic
      flux analysis (MFA). A pseudo steady state metabolic flux network model was
      constructed and analyzed using experimentally measured glycerol uptake rate and
      fluxes of four metabolites, viz. acetate, butyrate, succinate and 1,3-PDO.
      Glycerol consumption increased by ~50% under sonication. Biohydrogen yield showed
      marked rise of ~40% with application of ultrasound. Butyrate and 1,3-PDO were the
      major products of glycerol metabolism. Sonication had major influence on carbon
      fluxes at the acetyl-CoA node. MFA results revealed enhanced flux towards
      butyrate under sonication, which was manifested in higher butyrate to acetate
      (B/A) ratio in products and greater H2 generation. Biohydrogen production was
      also a microbial growth associated process. Finally, two theoretical alternatives
      for further enhancement of biohydrogen production were assessed with MFA, viz.
      enhancement of glycerol uptake and blocking of butyrate pathway.

PMID- 28456453
TI  - Gender Differences in Factors Associated with Unsheltered Status and Increased
      Risk of Premature Mortality among Individuals Experiencing Homelessness.
AB  - BACKGROUND: Among individuals experiencing homelessness, unsheltered status is
      associated with poor health and access to care and an increased risk for
      premature death. Insufficient research has explored gender differences in these
      outcomes; the objective of this study was to address this gap in the research.
      METHODS: This study used survey data collected during the 100,000 Homes Campaign.
      Chi-square tests identified differences in the characteristics of women, men, and
      transgender individuals. Generalized linear mixed models fit with demographic,
      homelessness, mental/behavioral health, institutional, and income characteristics
      were run separately for women and men to assess correlates of unsheltered status
      and increased risk of premature mortality. RESULTS: Men reported more frequently
      experiencing unsheltered homelessness while women and transgender participants
      more frequently met the criteria for risk of premature mortality. Women reported
      less frequently than men a history of or current substance use, but it
      significantly increased their likelihood of unsheltered homelessness; reports of
      mental health issues were rarer among men but significantly increased their odds
      of unsheltered homelessness. The experience of a violent attack while homeless
      was most strongly related to increased risk of premature mortality for both women
      and men. CONCLUSIONS: Interventions to reduce unsheltered homelessness among men
      should be particularly sensitive to mental health issues while for women there
      may need to be increased attention to substance use. A focus on experience of
      trauma and the provision of trauma-informed care is essential to address the
      increased risk of premature mortality among both men and women experiencing
      homelessness.

PMID- 28456455
TI  - Optimization of greenhouse gas emissions in second-hand consumer product recovery
      through reuse platforms.
AB  - Product reuse in the solid waste management sector is promoted as one of the key
      strategies for waste prevention. This practice is considered to have favorable
      impact on the environment, but its benefits have yet to be established. Existing
      research describes the perspective of "avoided production" only, but has failed
      to examine the interdependent nature of reuse practices within an entire solid
      waste management system. This study proposes a new framework that uses
      optimization to minimize the greenhouse gas emissions of an integrated solid
      waste management system that includes reuse strategies and practices such as
      reuse enterprises, online platforms, and materials exchanges along with
      traditional solid waste management practices such as recycling, landfilling, and
      incineration. The proposed framework uses material flow analysis in combination
      with an optimization model to provide the best outcome in terms of GHG emissions
      by redistributing product flows in the integrated solid waste management system
      to the least impacting routes and processes. The optimization results provide a
      basis for understanding the contributions of reuse to the environmental benefits
      of the integrated solid waste management system and the exploration of the
      effects of reuse activities on waste prevention. A case study involving second
      hand clothing is presented to illustrate the implementation of the proposed
      framework as applied to the material flow. Results of the case study showed the
      considerable impact of reuse on GHG emissions even for small replacement rates,
      and helped illustrate the interdependency of the reuse sector with other waste
      management practices. One major contribution of this study is the development of
      a framework centered on product reuse that can be applied to identify the best
      management strategies to reduce the environmental impact of product disposal and
      to increase recovery of reusable products.

PMID- 28456456
TI  - Full-scale treatment of landfill leachate by using the mechanical vapor
      recompression combined with coagulation pretreatment.
AB  - Landfill leachate contains high concentrations of organic compounds and ammonium,
      and the presence of heavy metal ions, which normally requires expensive and
      complex treatment processes. In this study, full-scale experiments were
      implemented to evaluate the feasibility of mechanical vapor recompression (MVR)
      treating leachate. Results revealed that despite the drastic changes of influent
      pollutant concentrations, MVR system possessed the ability to reduce most of the
      pollutants and guarantee the effluent in compliance with the discharge limits of
      Chinese Standard. Fouling analyses revealed that the main components in the
      fouling were crystalline (Mg0.06Ca0.94)(CO3), combining with humus and silicon
      compounds. A fouling cleaning method was developed with the adding sequence of
      first sulphamic acid and then NaOH, which could remove 88.62% fouling. Although
      fouling was inevitable for MVR treating leachate, coagulation pretreatment
      removed large amounts of COD, BOD5, total nitrogen, ammonium and total
      phosphorus, with the respective means of 68.4%, 69.4%, 81.0%, 84.1% and 81.4%,
      and thereafter reduced the treatment cost 27.4% from 47.06 RMB (6.92 US
      dollars)/m3 to 34.15 RMB (5.02 US dollars)/m3. These outcomes provided that in
      addition to the combination method of biological removal process with membrane
      technology, MVR process was another feasible solution for leachate treatment.

PMID- 28456457
TI  - Improvement in biohythane production using organic solid waste and distillery
      effluent.
AB  - Biohythane is a two-stage anaerobic fermentation process consisting of
      biohydrogen production followed by biomethanation. This serves as an environment
      friendly and economically sustainable approach for the improved valorization of
      organic wastes. The characteristics of organic wastes depend on their respective
      sources. The choice of an appropriate combination of complementary organic wastes
      can vastly improve the bioenergy generation besides achieving the significant
      cost reduction. The present study assess the suitability and economic viability
      of using the groundnut deoiled cake (GDOC), mustard deoiled cake (MDOC),
      distillers' dried grain with solubles (DDGS) and algal biomass (AB) as a co
      substrate for the biohythane process. Results showed that maximum gaseous energy
      of 23.93, 16.63, 23.44 and 16.21kcal/L were produced using GDOC, MDOC, DDGS and
      AB in the two stage biohythane production, respectively. Both GDOC and DDGS were
      found to be better co-substrates as compared to MDOC and AB. The maximum
      cumulative hydrogen and methane production of 150 and 64mmol/L were achieved
      using GDOC. 98% reduction in substrate input cost (SIC) was achieved using the co
      supplementation procedure.

PMID- 28456458
TI  - Chemical pretreatment of lignocellulosic agroindustrial waste for methane
      production.
AB  - This study investigates the effect of different chemical pretreatments on the
      solubilization and the degradability of different solid agroindustrial waste,
      namely winery waste, cotton gin waste, olive pomace and juice industry waste.
      Eight different reagents were investigated, i.e. sodium hydroxide (NaOH), sodium
      bicarbonate (NaHCO3), sodium chloride (NaCl), citric acid (H3Cit), acetic acid
      (AcOH), hydrogen peroxide (H2O2), acetone (Me2CO) and ethanol (EtOH), under three
      condition sets resulting in treatments of varying intensity, depending on process
      duration, reagent dosage and temperature. Results indicated that chemical
      pretreatment under more severe conditions is more effective on the solubilization
      of lignocellulosic substrates, such as those of the present study and among the
      investigated reagents, H3Cit, H2O2 and EtOH appeared to be the most effective to
      this regard. At the same time, although chemical pretreatment in general did not
      improve the methane potential of the substrates, moderate to high severity
      conditions were found to generally be the most satisfactory in terms of methane
      production from pretreated materials. In fact, moderate severity treatments using
      EtOH for winery waste, H3Cit for olive pomace and H2O2 for juice industry waste
      and a high severity treatment with EtOH for cotton gin waste, resulted in maximum
      specific methane yield values. Ultimately, the impact of pretreatment parameters
      on the different substrates seems to be dependent on their characteristics, in
      combination with the specific mode of action of each reagent. The overall energy
      balance of such a system could probably be improved by using lower operating
      powers and higher solid to liquid ratios.

PMID- 28456459
TI  - Comparative study of linkage between environmental policy instruments and
      technological innovation: Case study on end-of-life vehicles technologies in
      Japan and EU.
AB  - A growing population and urbanization is a challenge for finite natural
      resources. Without strict regulation to recycle, recover and reuse resources,
      waste is discarded with no value. Every year throughout the world, more than
      twenty-five million vehicles turn into end-of-life vehicles (ELV) and most of
      their valuable resources end up in landfill sites. This research analyses the
      effect of regulation on ELV innovation for additional recovery of resources in
      Japan and EU nations using patent data as a proxy. The analysis determines the
      statistical difference in patent activity before and after regulations were
      enacted in the case studies. The relevant data on ELV technologies was gathered
      for the period 1985-2013. The study suggests that in general environmental
      regulation in Japan drove innovation and reveals that environmental policy in
      Japan was more effective in enabling innovation compared to EU nations.
      Specifically, the results from these developed countries can be used by the
      rapidly growing developing countries in automobile manufacturing like China for
      amendment of their ELV regulation accordingly.

PMID- 28456460
TI  - Partitioning light spectra: Adaptive stratification of phytobenthic communities
      in Antarctic lakes.
AB  - Competition for light has an important influence for phototrophic community
      structures, especially, along the perpendicular axis. Here we develop a
      mathematical model for perpendicular community buildup of phototrophic species
      that differ in light absorption spectra and compete for incident light. Details
      of photon capture efficiencies and the roles of photoinhibition were taken into
      consideration to define species' fitness. Our theory showed that, if there is
      strong light irradiation due, for example, to the high transparency of the water
      in freshwater lakes in Antarctica, protective absorption of light should occur
      near the surface and photosynthetic absorption should gradually increase with
      depth. These results were then validated in comparison with observed vertical
      distributions of pigments in phytobenthic-mat communities from Antarctic lakes.

PMID- 28456461
TI  - The selfish herd: Noise effects in Local Crowded Horizon and Voronoi models.
AB  - Randomness or noise in the motion of herding animals is more important than
      commonly assumed. We show through simulations that noise promotes the compactness
      of a herd by facilitating the breakup of small clusters in favor of a more
      compact whole, reducing the mean median distances to center (MMDC) for the herd.
      Adding noise to movement models can also decrease risk from predators emerging
      locally by reducing Domains of Danger (DODs); we specifically show that adding
      noise to the Voronoi (V) movement model gives favorable DOD results comparable to
      that of the Local Crowded Horizon (LCH) model. In addition, we show that adding
      noise to these models can significantly reduce risk from predators emerging
      outside the herding area through head-to-head competition in mixed herds, with
      effects that can be larger than the choice of model itself. Our results are
      consistent with recent observational studies in several different animal
      populations that suggest random motion plays a significant role in the movement
      of individuals within these groups. Because of its significance, noise must be
      considered whenever model effectiveness is discussed or comparisons between
      movement models are made.

PMID- 28456462
TI  - Analysis of stability to cheaters in models of antibiotic degrading microbial
      communities.
AB  - Antibiotic resistance carried out by antibiotic degradation has been suggested
      recently as a new mechanism to maintain coexistence of microbial species
      competing on a single limiting resource, even in well-mixed homogeneous
      environments. Species diversity and community stability, however, critically
      depend on resistance against social cheaters, mutants that do not invest in
      production, but still enjoy the benefits provided by others. Here we investigate
      how different mutant cheaters affect the stability of antibiotic producing and
      degrading microbial communities. We consider two cheater types, production and
      degradation cheaters. We generalize the mixed inhibition-zone and chemostat
      models introduced previously [Kelsic, E. D., Zhao, J., Vetsigian, K., Kishony,
      R., 2015. Counteraction of an tibiotic production and degradation stabilizes
      microbial communities. Nature521, 516-519.] to study the population dynamics of
      microbial communities in well-mixed environment, and analyze the invasion of
      different cheaters in these models. We show that production cheaters, mutants
      that cease producing antibiotics, always destroy coexistence whenever there is a
      cost of producing these antibiotics. Degradation cheaters, mutants that loose
      their function of producing extracellular antibiotic degrading molecules, induce
      community collapse only if the cost of producing the degradation factors is above
      a critical level. Our analytical studies, supported by numerical simulations,
      highlight the sensitivity of antibiotic producing and degrading communities to
      loss-of-function mutants.

PMID- 28456463
TI  - Regime shifts and ecological catastrophes in a model of plankton-oxygen dynamics
      under the climate change.
AB  - It is estimated that more than a half of the total atmospheric oxygen is produced
      in the oceans due to the photosynthetic activity of phytoplankton. Any
      significant decrease in the net oxygen production by phytoplankton is therefore
      likely to result in the depletion of atmospheric oxygen and in a global mass
      mortality of animals and humans. In its turn, the rate of oxygen production is
      known to depend on water temperature and hence can be affected by the global
      warming. We address this problem theoretically by considering a model of a
      coupled plankton-oxygen dynamics where the rate of oxygen production slowly
      changes with time to account for the ocean warming. We show that, when the
      temperature rises sufficiently high, a regime shift happens: the sustainable
      oxygen production becomes impossible and the system's dynamics leads to fast
      oxygen depletion and plankton extinction. We also consider a scenario when, after
      a certain period of increase, the temperature is set on a new higher yet
      apparently safe value, i.e. before the oxygen depletion disaster happens. We show
      that in this case the system dynamics may exhibit a long-term quasi-sustainable
      dynamics that can still result in an ecological disaster (oxygen depletion and
      mass extinctions) but only after a considerable period of time. Finally, we
      discuss the early warning signals of the approaching regime shift resulting in
      the disaster.

PMID- 28456464
TI  - Laryngeal Closure during Swallowing in Stroke Survivors with Cortical or
      Subcortical Lesion.
AB  - BACKGROUND: One of the major, and most harmful, symptoms of dysphagia in stroke
      survivors is aspiration. Survivors of unilateral cortical strokes with dysphagia
      and resulting aspiration have been reported to have greater initiation delays in
      laryngeal closure than those who did not aspirate. Few studies have reported such
      data in survivors of subcortical stroke. METHODS: This study measured initiation
      of laryngeal closure (ILC) and laryngeal closure duration (LCD) in 2 groups of
      subjects: 15 stroke survivors with cortical lesions and 15 stroke survivors with
      subcortical lesions. Means and standard deviations of ILC and LCD were analyzed
      on 5-mL thin liquid and 5-mL puree boluses using a 100-ms timer during subsequent
      analysis of videofluoroscopic swallowing examinations. Statistical comparisons
      were used by repeated measures analysis of variance. Significance level was set
      at P < .05. RESULTS: ILC was significantly longer in stroke survivors with a
      subcortical lesion than in those with a cortical lesion for both bolus
      consistencies. However, there were no significant differences between the 2
      groups in LCD. Stroke survivors with a subcortical lesion had a greater incidence
      of penetration or aspiration and silent aspiration than those with a cortical
      lesion and a longer delay in the ILC. CONCLUSIONS: Subcortical lesions may put
      these survivors at greater risk of aspiration due to delayed initial laryngeal
      closure and reduced oral and laryngeal sensation. The subcortical damage, which
      occurs at the basal ganglia, may interrupt the ILC.

PMID- 28456466
TI  - Constitutive WNT/CTNNB1 activation triggers spermatogonial stem cell
      proliferation and germ cell depletion.
AB  - The differentiation of germ cells into oogonia or spermatogonia is the first step
      that eventually gives rise to fully mature gametes. In the female fetal gonad,
      the RSPO1/WNT/CTNNB1 signalling pathway is involved in primordial germ cell
      proliferation and differentiation into female germ cells, which are able to enter
      meiosis. In the postnatal testis, the WNT/CTNNB1 pathway also mediates
      proliferation of spermatogonial stem cells and progenitor cells. Here we show
      that forced activation of the WNT/CTNNB1 pathway in fetal gonocytes using
      transgenic mice leads to deregulated spermatogonial proliferation, and exhaustion
      of the spermatocytes by apoptosis, resulting in a hypoplastic testis. These
      findings demonstrate that a finely tuned timing in WNT/CTNNB1 signalling activity
      is required for spermatogenesis.

PMID- 28456465
TI  - Fine Particulate Matter (PM2.5) and the Risk of Stroke in the REGARDS Cohort.
AB  - BACKGROUND: Ambient particulate matter has been shown to be associated with
      declining human health, although the association between fine particulate matter
      (PM2.5) and stroke is uncertain. METHODS: We utilized satellite-derived measures
      of PM2.5 to examine the association between exposure and stroke in the REasons
      for Geographic And Racial Differences in Stroke (REGARDS) study. We used a time
      stratified case-crossover design, with exposure lags of 1 day, 2 days, and 3
      days. We examined all strokes, as well as ischemic and hemorrhagic strokes
      separately. RESULTS: Among 30,239 participants in the REGARDS study, 746 incident
      events were observed: 72 hemorrhagic, 617 ischemic, and 57 of unknown type.
      Participants exposed to higher levels of PM2.5 more often resided in urban areas
      compared to rural, and in the southeastern United States. After adjustment for
      temperature and relative humidity, no association was observed between PM2.5
      exposure and stroke, regardless of the lag (1-day lag OR = .99, 95% CI: .83-1.19;
      2-day lag OR = .95, 95% CI: .80-1.14; 3-day lag OR = .95, 95% CI = .79-1.13).
      Similar results were observed for the stroke subtypes. CONCLUSIONS: In this large
      cohort of African-Americans and whites, no association was observed between PM2.5
      and stroke. The ability to examine this association with a large number of
      outcomes and by stroke subtype helps fill a gap in the literature examining the
      association between PM2.5 and stroke.

PMID- 28456468
TI  - Lipid profile disturbances in antipsychotic-naive patients with first-episode non
      affective psychosis: Authors' reply.

PMID- 28456467
TI  - Dysfunctional T cell metabolism in the tumor microenvironment.
AB  - Metabolic and signaling pathways are integrated to determine T cell fate and
      function. As stimulated T cells gain distinct effector functions, specific
      metabolic programs and demands are also adopted. These changes are essential for
      T cell effector function, and alterations or dysregulation of metabolic pathways
      can modulate T cell function. One physiological setting that impacts T cell
      metabolism is the tumor microenvironment. The metabolism of cancer cells
      themselves can limit nutrients and accumulate waste products. In addition to the
      expression of inhibitory ligands that directly modify T cell physiology, T cell
      metabolism may be strongly inhibited in the tumor microenvironment. This
      suppression of T cell metabolism may inhibit effector T cell activity while
      promoting suppressive regulatory T cells, and act as a barrier to effective
      immunotherapies. A thorough understanding of the effect of the tumor
      microenvironment on the immune system will support the continued improvement of
      immune based therapies for cancer patients.

PMID- 28456469
TI  - Application of a portable microscopic cell counter for the counting of residual
      leukocytes in leukoreduced apheresis platelet concentrates in a hospital blood
      bank.
AB  - While a portable microscopic cell counter has been evaluated to enumerate
      residual white blood cells (WBCs) in red blood cells and platelet concentrates at
      blood centers, it has not yet been assessed in a hospital blood bank. We
      investigated the performance of this device and evaluated its accuracy, along
      with its benefits in time management. Residual WBCs from each of 100 apheresis
      platelet specimens were measured manually using a Nageotte chamber, along with
      flow cytometry methods and an ADAM-rWBC automated instrument (NanoEnTek, Seoul,
      South Korea). The efficiency was calculated by measuring the time required for
      the analysis of one specimen ten times consecutively. Flow cytometry and the ADAM
      rWBC were able to detect four sporadic cases that had residual WBCs exceeding
      1/MUL that were not detected by the manual method. Analysis time was the shortest
      with the ADAM-rWBC, followed by flow cytometry and the manual method. Our data
      suggest that hospital blood banks require quality control of residual WBCs; among
      the methods evaluated in this study, the portable microscopic cell counter offers
      the best time efficiency.

PMID- 28456470
TI  - Simple and rapid method for isolation and quantitation of polyhydroxyalkanoate by
      SDS-sonication treatment.
AB  - We developed a new method for isolation and quantitation of polyhydroxyalkanoate
      (PHA) from culture broth. In this method, the cells were sonicated in sodium
      dodecyl sulfate (SDS) solution and centrifuged to recover PHA. The recovered PHA
      was rinsed with deionized water and ethanol, and then weighed after drying.
      Hazardous chemicals such as chloroform, methanol, and sulfuric acid were not
      used, and no expensive analytical instruments were needed. We applied this method
      to Cupriavidus necator culture broths that included various amounts of poly(3
      hydroxybutyrate) (PHB) or poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)
      from flasks and jar fermentors. The quantitation by this method was practical for
      use with a wide range of production amounts and PHA monomer compositions compared
      to the conventional whole-cell methanolysis method with gas chromatographic
      analysis, and besides, the recovered PHAs were adequately pure (>=96% purity).
      Therefore, this new method would be valuable not only for quantitation of PHA but
      also for preparation of samples to characterize their mechanical properties.

PMID- 28456471
TI  - "I Can't Go Out": Mobility Obstacles to Women's Access to HIV Treatment in KPK,
      Pakistan.
AB  - We examined the role of outside mobility constraints as barriers to HIV treatment
      for Pakistani women living with HIV (WLWH) whose husbands were permanently living
      in other cities. We focused on Khyber Pakhtunkhwa (KPK), which adheres to
      conservative social and cultural values for female mobility. Open-ended
      interviews were conducted with 21 WLWH. We found that women's mobility outside
      the home was shaped by the system of parda (seclusion) and that a husband's lack
      of support by not being present for clinical appointments, distance to the HIV
      clinic, and ages of children emerged as crucial contributors to women's outside
      mobility and their subsequent abilities to access HIV care. These obstacles were
      more acute for women living with in-laws rather than in nuclear families.
      Policymakers need to better understand the nuances of local cultures in which
      women seek HIV treatment so that they can devise practical, culturally
      appropriate, and acceptable programs.

PMID- 28456472
TI  - A Review of Risk Behaviors for HIV Infection by Men Who Have Sex With Men Through
      Geosocial Networking Phone Apps.
AB  - The purpose of our review was to analyze the relationship between the use of
      geosocial networking phone apps and risk behaviors for HIV infection in men who
      have sex with men (MSM). The review was guided by the question: Does the use of
      geosocial networking apps to find sex partners increase risk behaviors for HIV
      infection by MSM? We searched the databases PubMed, Web of Science, CINAHL, and
      LILACS, considering primary studies published up to December 2015, without any
      time restraint. All 14 studies that met our search criteria analyzed sexual
      behaviors in relation to sociocultural and economic characteristics, number of
      partners, unprotected anal sex, drug use, HIV testing, risk management measures,
      and the presence of other sexually transmitted diseases. The results indicated
      that use of geosocial networking apps to find sex partners may lead to new
      patterns of behavior and relationships that place MSM at risk for HIV.

PMID- 28456474
TI  - Developing a Progressive Control Pathway for African Animal Trypanosomosis.
AB  - Progressive control pathways (PCPs) are stepwise approaches for the reduction,
      elimination, and eradication of human and animal diseases. They provide
      systematic frameworks for planning and evaluating interventions. Here we outline
      a PCP for tsetse-transmitted animal trypanosomosis, the scourge of poor livestock
      keepers in tropical Africa. Initial PCP stages focus on the establishment of
      national coordination structures, engagement of stakeholders, development of
      technical capacities, data collection and management, and pilot field
      interventions. The intermediate stage aims at a sustainable and economically
      profitable reduction of disease burden, while higher stages target elimination.
      The mixed-record of success and failure in past efforts against African animal
      trypanosomosis (AAT) makes the development of this PCP a high priority.

PMID- 28456473
TI  - Continuing Links Between Substance Use and HIV Highlight the Importance of
      Nursing Roles.
AB  - Links between HIV and substance use were identified early in the U.S. HIV
      epidemic. People who use drugs are at risk of HIV infection through shared
      injection equipment and risky sexual behaviors. In addition, substance use has
      negative health consequences for people living with HIV. The prescription opioid
      misuse epidemic, linked to injection drug use, hepatitis C infection, and HIV,
      poses a new threat to declining HIV rates. We reviewed evidence-based
      interventions that decrease HIV risk in people who use drugs (needle/syringe
      programs, medication-assisted treatment, engagement in HIV care, and preexposure
      prophylaxis/postexposure prophylaxis). The critical roles of nurses in HIV
      prevention/care for this population are described, including applying the
      principles of harm reduction, screening for substance use, and undertaking
      implementation and research efforts. As the nation's largest health care
      profession, nurses are positioned to contribute to the quality of HIV-related
      prevention/care for people who use drugs and to lead practice initiatives.

PMID- 28456475
TI  - Advanced glycation end products and strontium ranelate promote osteogenic
      differentiation of vascular smooth muscle cells in vitro: Preventive role of
      vitamin D.
AB  - Advanced glycation end products (AGE) have been demonstrated to induce the
      osteogenic trans-differentiation of vascular smooth muscle cells (VSMC).
      Strontium ranelate (SR) is an anti-osteoporotic agent that has both anti
      catabolic and anabolic actions on bone tissue. However, in the last years SR has
      been associated with an increase of cardiovascular risk. We hypothesize that SR
      can increase the osteoblastic trans-differentiation of VSMC and the induction of
      extracellular calcifications, an effect that could be potentiated in the presence
      of AGE and inhibited by simultaneous administration of vitamin D. The present
      results of our in vitro experiments demonstrate that AGE and SR alone or in
      combination, stimulate L-type calcium channels, causing an increase in reactive
      oxygen species and activation of both ERK and NFkB, with the final effect of
      promoting the osteogenic shift of VSMC. Importantly, these in vitro effects of
      AGE and/or SR can be prevented by co-incubation with vitamin D.

PMID- 28456477
TI  - Human papillomavirus-associated oropharyngeal cancer: Prioritizing preventive
      policies in males.

PMID- 28456476
TI  - The acute effect of cannabis on plasma, liver and brain ammonia dynamics, a
      translational study.
AB  - Recent reports of ammonia released during cannabis smoking raise concerns about
      putative neurotoxic effects. Cannabis (54mg) was administered in a double-blind,
      placebo-controlled design to healthy cannabis users (n=15) either orally, or
      through smoking (6.9%THC cigarette) or inhalation of vaporized cannabis
      (Volcano(r)). Serial assay of plasma ammonia concentrations at 0, 2, 4, 6, 8, 10,
      15, 30, and 90min from onset of cannabis administration showed significant time
      (P=0.016), and treatment (P=0.0004) effects with robust differences between
      placebo and edible at 30 (P=0.002), and 90min (P=0.007) and between placebo and
      vaporized (P=0.02) and smoking routes (P=0.01) at 90min. Furthermore, plasma
      ammonia positively correlated with blood THC concentrations (P=0.03). To test the
      hypothesis that this delayed increase in plasma ammonia originates from the brain
      we administered THC (3 and 10mg/kg) to mice and measured plasma, liver, and brain
      ammonia concentrations at 1, 3, 5 and 30min post-injection. Administration of THC
      to mice did not cause significant change in plasma ammonia concentrations within
      the first 5min, but significantly reduced striatal glutamine-synthetase (GS)
      activity (P=0.046) and increased striatal ammonia concentration (P=0.016).
      Furthermore, plasma THC correlated positively with striatal ammonia concentration
      (P<0.001) and negatively with striatal GS activity (P=0.030). At 30min, we found
      marked increase in striatal ammonia (P<0.0001) associated with significant
      increase in plasma ammonia (P=0.042) concentration. In conclusion, the results of
      these studies demonstrate that cannabis intake caused time and route-dependent
      increases in plasma ammonia concentrations in human cannabis users and reduced
      brain GS activity and increased brain and plasma ammonia concentrations in mice.

PMID- 28456478
TI  - Why are we still unable to accurately determine the malignant potential or the
      behavior of oral mucosal lesions?

PMID- 28456480
TI  - Imaging the ageing brain: identifying early disease or opening Pandora's box?

PMID- 28456479
TI  - Age-specific and sex-specific prevalence of cerebral beta-amyloidosis, tauopathy,
      and neurodegeneration in cognitively unimpaired individuals aged 50-95 years: a
      cross-sectional study.
AB  - BACKGROUND: A new classification for biomarkers in Alzheimer's disease and
      cognitive ageing research is based on grouping the markers into three categories:
      amyloid deposition (A), tauopathy (T), and neurodegeneration or neuronal injury
      (N). Dichotomising these biomarkers as normal or abnormal results in eight
      possible profiles. We determined the clinical characteristics and prevalence of
      each ATN profile in cognitively unimpaired individuals aged 50 years and older.
      METHODS: All participants were in the Mayo Clinic Study of Aging, a population
      based study that uses a medical records linkage system to enumerate all
      individuals aged 50-89 years in Olmsted County, MN, USA. Potential participants
      are randomly selected, stratified by age and sex, and invited to participate in
      cognitive assessments; individuals without medical contraindications are invited
      to participate in brain imaging studies. Participants who were judged clinically
      as having no cognitive impairment and underwent multimodality imaging between Oct
      11, 2006, and Oct 5, 2016, were included in the current study. Participants were
      classified as having normal (A-) or abnormal (A+) amyloid using amyloid PET,
      normal (T-) or abnormal (T+) tau using tau PET, and normal (N-) or abnormal (N+)
      neurodegeneration or neuronal injury using cortical thickness assessed by MRI. We
      used the cutoff points of standard uptake value ratio (SUVR) 1.42 (centiloid 19)
      for amyloid PET, 1.23 SUVR for tau PET, and 2.67 mm for MRI cortical thickness.
      Age-specific and sex-specific prevalences of the eight groups were determined
      using multinomial models combining data from 435 individuals with amyloid PET,
      tau PET, and MRI assessments, and 1113 individuals who underwent amyloid PET and
      MRI, but not tau PET imaging. FINDINGS: The numbers of participants in each
      profile group were 165 A-T-N-, 35 A-T+N-, 63 A-T-N+, 19 A-T+N+, 44 A+T-N-, 25
      A+T+N-, 35 A+T-N+, and 49 A+T+N+. Age differed by ATN group (p<0.0001), ranging
      from a median 58 years (IQR 55-64) in A-T-N- and 57 years (54-64) in A-T+N- to a
      median 80 years (75-84) in A+T-N+ and 79 years (73-87) in A+T+N+. The number of
      APOE epsilon4 carriers differed by ATN group (p=0.04), with carriers roughly
      twice as frequent in each A+ group versus the corresponding A- group. White
      matter hyperintensity volume (p<0.0001) and cognitive performance (p<0.0001) also
      differed by ATN group. Tau PET and neurodegeneration biomarkers were discordant
      in most individuals who would be categorised as stage 2 or 3 preclinical
      Alzheimer's disease (A+T+N-, A+T-N+, and A+T+N+; 86% at age 65 years and 51% at
      age 80 years) or with suspected non-Alzheimer's pathophysiology (A-T+N-, A-T-N+,
      and A-T+N+; 92% at age 65 years and 78% at age 80 years). From age 50 years, A-T
      N- prevalence declined and A+T+N+ and A-T+N+ prevalence increased. In both men
      and women, A-T-N- was the most prevalent until age late 70s. After about age 80
      years, A+T+N+ was most prevalent. By age 85 years, more than 90% of men and women
      had one or more biomarker abnormalities. INTERPRETATION: Biomarkers of fibrillar
      tau deposition can be included with those of beta-amyloidosis and
      neurodegeneration or neuronal injury to more fully characterise the heterogeneous
      pathological profiles in the population. Both amyloid- dependent and amyloid
      independent pathological profiles can be identified in the cognitively unimpaired
      population. The prevalence of each ATN group changed substantially with age, with
      progression towards more biomarker abnormalities among individuals who remained
      cognitively unimpaired. FUNDING: National Institute on Aging (part of the US
      National Institutes of Health), the Alexander Family Professorship of Alzheimer's
      Disease Research, the Mayo Clinic, and the GHR Foundation.

PMID- 28456481
TI  - Significance of Anemia in Outcomes After Neoadjuvant Chemoradiotherapy for
      Locally Advanced Rectal Cancer.
AB  - BACKGROUND: Approximately one quarter of patients receiving neoadjuvant
      chemoradiotherapy (NCRT) for locally advanced rectal cancer will be anemic at
      presentation. The outcomes of these anemic patients have historically been less
      favorable. We assessed the potential of anemia to act as an independent biomarker
      for a poor prognosis in patients with locally advanced rectal cancer. MATERIALS
      AND METHODS: We performed a retrospective, observational study of consecutive
      patients with locally advanced rectal adenocarcinoma who underwent NCRT from 2004
      to 2009 at 3 English National Health Service trusts. The main outcomes were
      Rectal Cancer Regression Grade, mortality rate, and disease-free survival. These
      were compared between the anemic and nonanemic patients. RESULTS: A total of 273
      patients were included. Of these patients, 63 (23%) had a hemoglobin level of <
      120 g/L (anemic) at presentation. The Rectal Cancer Regression Grades were higher
      (less regression) in the anemic patients than in the nonanemic patients (chi2 =
      10.14; P = .006). A subgroup analysis stratified by disease stage at presentation
      demonstrated less tumor regression in anemic patients with Dukes stage C disease
      (Dukes stage B, chi2 = 4.31, P = .12; Dukes stage C, chi2 = 5.36, P = .07). After
      adjusting for age, gender, and initial Dukes stage, the anemic patients
      demonstrated greater mortality rates than the nonanemic patients (hazard ratio,
      1.73; 95% confidence interval, 1.05-2.86). The consistency with which the 2
      independent reviewers were able to generate the rectal cancer regression grades
      from the historic pathology reports varied. Also, the subgroup analyses in the
      present study were often limited by low power. CONCLUSION: The present large UK
      study examined patients receiving NCRT for magnetic resonance imaging-proven,
      locally advanced rectal adenocarcinoma. Our findings have demonstrated that
      patients who were anemic at presentation have higher regression grades (less
      regression) in response to the treatment than nonanemic patients. This trend
      appeared to persist despite radiologic disease stage at presentation. Anemia at
      presentation was also associated with increased mortality rates compared with
      that of nonanemic patients.

PMID- 28456482
TI  - Hospital costs and cost implications of co-morbid conditions for patients with
      single ventricle in the period through to Fontan completion.
AB  - BACKGROUND: Patients undergoing palliative surgeries for single-ventricle
      conditions are affected by multiple comorbidities or non-cardiac conditions. The
      prevalence, costs and the cost implications of these conditions have not been
      assessed. METHODS: Administrative costing records from four hospitals in
      Australia and New Zealand were linked with the Fontan registry database to
      analyze the inpatient resource use for co-morbid or non-cardiac conditions.
      Inpatient costing records from the birth year through to Fontan completion were
      available for 156 patients. The most frequent primary diagnoses were hypoplastic
      left heart syndrome (33%), double inlet left ventricle (13%), and tricuspid
      atresia (12%). RESULTS: During the staged surgical treatment period, children had
      a mean of 10+/-6 inpatient admissions and spent 85+/-64days in hospital. Among
      these admissions, 3+/-5 were for non-cardiac conditions, totaling 21+/-41
      inpatient days. Whilst cardiac surgeries were the major reason for resource use
      (77% of the total cost), other cardiac care that is not surgical contributed 5%
      and non-cardiac admissions 18% of the total cost. The three most prevalent non
      cardiac diagnostic admission categories were 'Respiratory system', 'Digestive
      system', and 'Ear, nose, mouth and throat', affecting 28%, 21% and 34% of the
      patients respectively. Multivariate regression estimated that admissions for each
      of these categories resulted in an increased cost of $34,563 (P=0.08), $52,438
      (P=0.05) and $10,525 (P=0.53) per patient respectively for the staged surgical
      treatment period. CONCLUSIONS: Non-cardiac admissions for single-ventricle
      patients are common and have substantial resource implications. Further research
      assessing the causes of admission and extent to which admissions are preventable
      is warranted.

PMID- 28456483
TI  - Characteristics and long-term catheter ablation outcome in long-standing
      persistent atrial fibrillation patients with non-pulmonary vein triggers.
AB  - BACKGROUND: There are limited literatures regarding the non-pulmonary vein (NPV)
      triggers in long-standing persistent atrial fibrillation (LSPAF). The goal of the
      present study was to investigate the characteristics and long-term outcome of
      catheter ablation among these patients. METHODS: The study included 776 patients
      (age 53.59+/-11.38years-old, 556 males) who received catheter ablation for drug
      refractory atrial fibrillation (AF). We divided these patients into 3 groups.
      Group 1 consisted of 579 patients with paroxysmal AF (PAF), group 2 consisted of
      103 patients with persistent AF (PerAF) and group 3 consisted of 94 patients with
      long-standing persistent AF (LSPAF). The average follow-up duration was 28.53+/
      23.21months. RESULTS: The clinical endpoint was the recurrence of atrial
      tachyarrhythmia. Among these 3 groups, higher percentages of male (93.6%,
      P<0.001), NPV triggers (44.7%, P<0.001), longer AF duration (6.65+/-6.72years,
      P=0.029), larger left atrium diameter (44.44+/-6.79mm, P<0.001), and longer
      procedure time (181.94+/-70.02min, P<0.001) were noted in LSPAF. After the first
      catheter ablation, the recurrence rate of AF was highest in LSPAF (Log Rank,
      P<0.001). Larger left atrium diameters (LAD) (P=0.006; HR: 1.063; CI: 1.018
      1.111) and NPV triggers (P=0.035; HR: 1.707; 1.037-2.809) independently predicted
      AF recurrence in LSPAF. CONCLUSIONS: Compared with PAF and PerAF, LSPAF had a
      higher incidence of NPV triggers and worse long-term outcome after catheter
      ablation. NPV triggers and LAD independently predicted AF recurrence after
      catheter ablation in LSPAF.

PMID- 28456484
TI  - Hypersensitivity reactions in patients receiving hemodialysis.
AB  - OBJECTIVE: To describe hypersensitivity reactions in patients receiving
      maintenance hemodialysis. DATA SOURCES: PubMed search of articles published
      during the past 30 years with an emphasis on publications in the past decade.
      STUDY SELECTIONS: Case reports and review articles describing hypersensitivity
      reactions in the context of hemodialysis. RESULTS: Pharmacologic agents are the
      most common identifiable cause of hypersensitivity reactions in patients
      receiving hemodialysis. These include iron, erythropoietin, and heparin, which
      can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and
      anesthetics, which lead to delayed-type hypersensitivity reactions. Many
      hypersensitivity reactions are triggered by complement activation and increased
      bradykinin resulting from contact system activation, especially in the context of
      angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic
      preparations and dialyzer membranes are available, such that once an etiology for
      the reaction is established, recurrences can be prevented without affecting the
      quality of care provided to patients. CONCLUSION: Although hypersensitivity
      reactions are uncommon in patients receiving hemodialysis, they can be life
      threatening. Moreover, considering the large prevalence of the end-stage renal
      disease population, the implications of such reactions are enormous. Most
      reactions are pseudoallergic and not mediated by immunoglobulin E. The
      multiplicity of potential exposures and the complexity of the environment to
      which patients on dialysis are exposed make it challenging to identify the
      precise cause of these reactions. Great diligence is needed to investigate
      hypersensitivity reactions to avoid recurrence in this high-risk population.

PMID- 28456485
TI  - Higher fractional exhaled nitric oxide and Der p 1 exposure in children with
      asthma living in tropical environments.

PMID- 28456486
TI  - Sodium Salicylate Inhibits Urokinase Activity in MDA MB-231 Breast Cancer Cells.
AB  - INTRODUCTION: Sodium salicylate (NaS) is a derivate of acetylsalicylic acid or
      aspirin, used as a nonsteroidal anti-inflammatory drug for centuries, for its
      analgesic and anti-inflammatory effects. It was found to modulate different
      signaling pathways, in a cell-specific way. Here, we explore the effect of NaS on
      cell growth and urokinase activity in MDA MB-231 breast cancer cells. MATERIALS
      AND METHODS: We analyzed the effect of NaS treatment on cell growth by flow
      cytometry and viability test. The transwell migration assay was used to study the
      migratory response of the cells. The gene expression was analyzed by qRT-PCR on
      RNA level and by Western blot analysis on protein level. Urokinase activity was
      assessed by caseinolysis. RESULTS: Sublethal concentrations of NaS decreased cell
      growth and inhibited urokinase activity. The latter was a consequence of decrease
      in urokinase expression and increase in expression of its inhibitors. Analysis of
      signaling molecules revealed activation of transforming growth factor-beta
      signaling, increase in master transcription factors for epithelial-mesenchymal
      transition and changes in integrin expression. CONCLUSIONS: We propose that NaS
      causes partial cellular reprogramming through transforming growth factor-beta
      signaling which, together with direct NaS influence, causes changes in expression
      in a set of genes involved in extracellular proteolysis. These data could be
      beneficial for the development of new therapeutic approaches in invasive breast
      cancer treatment.

PMID- 28456487
TI  - Interval Breast Cancer Versus Screen-Detected Cancer: Comparison of
      Clinicopathologic Characteristics in a Single-Center Analysis.
AB  - BACKGROUND: The introduction of breast screening programs has raised the problem
      of interval breast cancers (IBC). The aims of this study were to analyze the
      impact of IBC on the screening program, to compare IBC and screen-detected
      cancers (SDC), and to identify possible predictors of mortality. PATIENTS AND
      METHODS: Patients with breast cancer diagnosed during the regional breast
      screening program between January 2008 and December 2013 at a single center in
      Italy were included. Demographic, preoperative, and postoperative data were
      prospectively collected and retrospectively analyzed. RESULTS: Five hundred
      thirty-four patients were enrolled; 106 women (19.9%) had IBC and 428 women
      (80.1%) SDC. IBC presented more aggressive features compared to SDC, such as
      tumor invasiveness (95% vs. 85%; P = .005), tumor size (>= pT2 37% vs. 21%; P =
      .001), grade (G3 39% vs. 17%; P < .001), and St Gallen molecular subtype (triple
      negative 22% vs. 7%; P < .001), resulting in higher distant recurrence rate (8%
      vs. 2%; P = .009) and worse overall and disease-free survival (P = .03 and P =
      .001, respectively). Cox multivariate regression analysis identified St Gallen
      molecular subtype as the only predictor of mortality in patients with breast
      cancer (P = .03). CONCLUSION: IBC accounted for one-fifth of all breast cancers
      diagnosed in women who followed the regional screening program. Furthermore, IBC
      appeared to have more aggressive features compared to SDC, leading to worse
      survival. These worse survivals depended on St Gallen molecular subtype.

PMID- 28456488
TI  - Secondary syphilis mimicking malignancy: A case report and review of literature.
AB  - A 56-year-old man developed disseminate lymphadenopathies, associated with hepato
      splenomegaly, fever, nocturnal sweating and weight loss. Imaging studies in
      particular FDG-PET/CT raised the suspicion of a malignant disease. But blood flow
      cytometry assay for B/T cell clonality was negative and fine-needle biopsy of
      enlarged laterocervical lymph node showed a not specific "reactive hyperplasia".
      Four months later, the patient developed a non-itching rash; since a further
      anamnestic investigation revealed an history of high-risk sexual intercourse, the
      patient underwent serological tests for Treponema pallidum that were positive at
      high titer, after a first negative screening. Made the diagnosis of secondary
      syphilis, the patient responded to the treatment with benzyl penicillin with
      complete resolution of symptoms. This case highlights the importance of carefully
      screening the patients with suspected lymphoadenopathies also for lue,
      particularly in presence of behavioral risk factors.

PMID- 28456489
TI  - Evaluation of commercial phenotypic assays for the detection of IMP- or New Delhi
      metallo-beta-lactamase-producing Enterobacteriaceae isolates in Japan.
AB  - OBJECTIVES: This study was designed to evaluate the sodium mercaptoacetic acid
      double disk synergy test (SMA-DDST), the Etest metallo-beta-lactamase (MBL)
      MP/MPI (Etest MP/MPI), and the Mastdiscs ID Carbapenemase Detection Disc Set
      (MAST-CDS) for the detection of MBL-producing Enterobacteriaceae isolates in
      Japan. METHODS: Fifty-one clinical isolates and four reference strains were
      tested. These isolates included 40, 4, and 11 IMP-, New Delhi MBL (NDM)-, and non
      MBL-producers, respectively. SMA-DDST was performed with meropenem (MEPM)
      containing disks. RESULTS: Sensitivities were 38/44 (86%), 40/44 (91%), and 15/44
      (34%), and the cost ratio was 1:9.4:3.8 for MEPM-SMA-DDST:Etest MP/MPI:MAST-CDS,
      respectively. The specificity was 11/11 (100%) for all assays. MEPM-SMA-DDST
      detected IMP-producing isolates with high sensitivity (38/40; 95%), but the assay
      was inadequate for NDM-producing isolates (0/4; 0%). The Etest MP/MPI detected
      both IMP- (36/40; 90%) and NDM-producing isolates (4/4; 100%), but was the most
      expensive. MAST-CDS detected IMP-producing isolates with low sensitivity (11/40;
      28%), but the assay worked well for NDM-producing isolates (4/4; 100%).
      CONCLUSIONS: Our results indicated that MEPM-SMA-DDST was the most cost-effective
      assay for the detection of IMP-producing isolates. Therefore, we conclude that
      MEPM-SMA-DDST is the optimal available assay for clinical first-line screening in
      IMP-endemic areas such as Japan. However, this assay could not detect NDM
      producing isolates, whereas the Etest MP/MPI and MAST-CDS could. When MEPM-SMA
      DDST is negative, the Etest MP/MPI and MAST-CDS could be used to obtain
      supportive data and prevent detection failure for NDM-producing isolates.

PMID- 28456490
TI  - Pediatric bacterial meningitis in Japan, 2013-2015 - 3-5 years after the wide use
      of Haemophilus influenzae type b and Streptococcus pneumoniae conjugated
      vaccines.
AB  - BACKGROUND: Haemophilus influenzae type b (Hib) vaccine and pneumococcal
      conjugated vaccine (PCV) have been widely used since 2010 in Japan when both
      vaccines were supported by the regional governments, and they were covered as
      routine recommended vaccines in 2013. The incidence of bacterial meningitis due
      to these organisms decreased in 2011 and 2012, but meningitis due to
      Streptococcus agalactiae and Escherichia coli remained unchanged. OBJECTIVES: We
      planned to confirm whether the incidence also decreased in subsequent years.
      METHODS: We analyzed the epidemiological and clinical data for 2013-2015, and
      compared the information obtained in the previous nationwide survey database and
      our previous reports. We also investigated the risk factors for disease outcome.
      RESULTS: In the 2013-2015 surveys, 407 patients from 366 hospitals from all
      prefectures were evaluated. S. agalactiae (33%), Streptococcus pneumoniae (25%),
      and E. coli (10%) were the main organisms. The total number of patients
      hospitalized with bacterial meningitis per 1000 admissions decreased from 1.19 in
      2009-2010 to 0.37 in 2013-2015 (p < 0.001). The incidence of H. influenzae and S.
      pneumoniae meningitis significantly decreased from 0.66 in 2009-2010 to 0.01 in
      2013-2015, and from 0.30 to 0.09, respectively (p < 0.001). Only 0-2 cases with
      Neisseria meningitidis were reported each year throughout 2001-2015. The fatality
      rates for H. influenzae, S. pneumoniae, S. agalactiae, and E. coli in 2013-2015
      were 0.0, 4.1, 3.1, and 2.6%, respectively. Risk factors for death and sequelae
      were consciousness disturbance, convulsion, low CSF glucose, and Staphylococcus
      sp. as a causative organism (p < 0.01). CONCLUSIONS: Hib vaccine and PCV have
      decreased the rate of bacterial meningitis. S. agalactiae has subsequently become
      the most common cause of bacterial meningitis in Japan.

PMID- 28456491
TI  - Past, present and future patient safety in healthcare organisations.

PMID- 28456492
TI  - Barriers to the implementation of research perceived by nurses from Osakidetza.
AB  - OBJECTIVE: To understand the barriers to implementing nursing research findings
      into practice, as perceived by the nurses working in Osakidetza and to analyze if
      the workplace factor and time worked affect the perception of these barriers.
      METHODS: Cross-sectional study. BARRIERS Scale questionnaire was given to a
      representative sample of 1,572 Basque Health Service nurses, stratified and
      randomized, according to scope of work and job responsibility (response rate:
      43.76%). RESULTS: According to the research results, the first important barrier
      was "insufficient time on the job to implement new ideas". Nurses have perceived
      the organizational factor as the most important barrier in their practice. Nurses
      in "Special hospital departments" perceived more barriers in the "quality of
      research" factor than those working in "Primary Care". Years of service showed a
      slight influence. CONCLUSIONS: The nurses stated that external factors related to
      the organization principally interfered in implementing results into clinical
      practice. They placed lack of critical reading training second. Working
      environment and seniority mark differences in the perception of barriers. This
      study may help to develop strategies for planning training programs to facilitate
      the use of research in clinical practice, in order to provide quality care.

PMID- 28456493
TI  - "Simulated gastric hydrolysis and developmental toxicity of dioctyltin bis(2
      Ethylhexylthioglycolate) [DOTE] in rabbits and mice".
AB  - Based on previous studies, dioctyltin dichloride [DOTC] was a putative toxophore
      for dioctyltin thioesters. Our results, generated with the use of 119Sn-NMR
      spectroscopy demonstrated that dioctyltin bis(2-ethylhexyl thioglycolate) [DOTE]
      hydrolyzed to form dioctyltin chloro-(2-ethylhexyl thioglycolate) [DOTCE] under
      simulated gastric conditions, but no DOTC was formed. DOTE was administered
      orally at 4, 20, and 80 mg/kg/day [GD6-GD28; rabbits] or at 15, 30, and 60
      mg/kg/day [GD5-GD17; mice]. There were no maternal deaths, treatment-related
      statistically significant reductions in maternal body weight or weight gain, or
      adverse gestational outcomes in either species. Maternal thymus weight was
      significantly reduced in mice at 30 and 60 mg/kg. There were no effects on fetal
      growth, no dose-dependent pattern of external, visceral or skeletal malformations
      and no increase in anatomical variations in either species. We conclude that DOTE
      likely forms DOTCE, not DOTC, in the stomach and DOTE was not teratogenic or
      fetotoxic in rabbits or mice. The rabbit maternal NOAEL was 80 mg/kg/day. The
      rabbit developmental NOAEL was 80 mg/kg/day. The mouse maternal LOAEL was 30
      mg/kg/day based on reduced thymus weight and a dose-dependent effect on maternal
      weight at 60 mg/kg. The mouse developmental NOAEL was 60 mg/kg bw/day, the high
      dose.

PMID- 28456494
TI  - Phosphoinositide binding profiles of the PX domains of Giardia lamblia.
AB  - The membrane trafficking machinery that functions at the endomembrane system of
      Giardia lamblia appears to be significantly different from that present in most
      model eukaryotes. This machinery is important for encystation as cyst wall
      material is trafficked to the cell surface via encystation-specific vesicles.
      Since proteins containing the phosphoinositide-binding PX domains are known
      regulators of vesicular trafficking, BLAST search was used to identify the PX
      domains of G. lamblia. Six putative PX domain-containing ORFs were identified.
      Some of the encoded PX domains contained non-canonical amino acid residues in the
      highly conserved ligand binding pocket. In vitro and in vivo binding studies
      indicate that these domains have the ability to bind to diverse
      phosphoinositides. Also, coincidence detection is likely to play a significant
      role in ligand binding in vivo since domains that bind to the same lipid in
      vitro, exhibit differences in subcellular localization. Analyses of the
      expression of these six genes in trophozoites, encysting trophozoites and cysts
      showed that while the expression of four of the genes were downregulated in
      cysts, the other two were upregulated. The variation in ligand preference of the
      individual PX domains and the differential expression of most of the PX-domain
      encoding genes indicate that these PX domain-containing proteins are likely to
      perform diverse cellular functions.

PMID- 28456495
TI  - Women's Leadership in the ACR, 2001-2015.
AB  - PURPOSE: To assess the trends of women in voluntary leadership roles in the ACR
      from 2001 to 2015. METHODS: Retrospective leadership records from 2001 to 2015
      were collected from the ACR Membership Database based on member demographics,
      gender, and participation in leadership roles at the national and state level.
      Data were sorted by gender and year to assess the proportion of women in each
      leadership position relative to total member/representation counts. RESULTS:
      Overall, there were increasing numbers of women represented in ACR leadership.
      From 2001 to 2015, there were increasing rates of women achieving fellowship in
      the College (7%-11%), now at parity with male member rates. Representation by
      women has risen from 7% to 21% for state chapter presidents and from 14% to 18%
      for state councilors. Comparing rolling 5-year averages from 2001-2005 and 2011
      2015 showed statistically significant increases (P < .05) in these leadership
      roles. Women members of the council steering committee rose from 13% in 2001 to
      19% in 2015, peaking at 24% in 2014. The Board of Chancellors (BOC) showed the
      largest increase in women, from 9% to 33%, with a peak at 37% in 2014. However,
      no BOC chairs were women, one council speaker was a woman, two women were ACR
      presidents, and two women were vice presidents. CONCLUSIONS: Women's
      participation in ACR leadership has increased significantly at the state level
      and in fellowship recognition. Although there are increasing numbers of women on
      the BOC, top positions remain male-dominated at the national level.

PMID- 28456496
TI  - Correction to Lancet Glob Health 2016; 4: e453-63.

PMID- 28456497
TI  - Smoking before isometric exercise amplifies myocardial stress and dysregulates
      baroreceptor sensitivity and cerebral oxygenation.
AB  - This crossover study examined whether acute cardiovascular responses,
      baroreceptor sensitivity (BRS), and brain oxygenation during isometric exercise
      are altered after cigarette smoking. Twelve young, habitual smokers randomly
      performed a smoking and a control protocol, during which participants smoked one
      cigarette (0.9 mg nicotine) or a sham cigarette, before exercise. Testing
      involved baseline, a 5-minute smoking, a 10-minute post-smoking rest, 3-minute
      handgrip exercise (30% maximum voluntary contraction), and recovery. Beat-to-beat
      blood pressure, heart rate (HR), and cerebral oxygenation (near infrared
      spectroscopy) were continuously monitored. Double-product, stroke volume (SV),
      cardiac output, systemic vascular resistance and BRS were assessed. During post
      smoking rest, systolic or diastolic blood pressure (140.8 +/- 12.1/87.0 +/- 6.9
      vs. 125.9 +/- 7.1/77.3 +/- 5.5 mm Hg), HR, and double product were higher in the
      smoking versus the control protocol, whereas BRS was lower (P < .05). During
      handgrip exercise, smoking resulted in greater HR and double product (17,240 +/-
      3893 vs. 15,424 +/- 3173 mm Hg.bpm) and lower BRS versus the control protocol (P
      < .05), without significant differences in stroke volume and systemic vascular
      resistance between protocols. During recovery, smoking elicited a delayed return
      of brain oxygenation indices, lower BRS, and higher double product. Smoking a
      cigarette shortly before the exercise session amplifies myocardial stress and
      dysregulates autonomic function and cerebral oxygenation during exercise and
      recovery, even in young habitual smokers, perceived as free from long-term
      cardiovascular effects of smoking.

PMID- 28456498
TI  - Fibroblast growth factor-23 is independently associated with cardiac mass in
      African-American adolescent males.
AB  - Left ventricular hypertrophy has been documented in hypertensive adolescents and
      among some with prehypertension. Obesity also appears to be associated with
      cardiac mass, independent of blood pressure (BP). Fibroblast growth factor 23
      (FGF23) is a novel biomarker positively associated with left ventricular
      hypertrophy in adults with and without kidney disease. The aim of this study was
      to determine if there was a significant and independent association of FGF23 with
      cardiac mass in a Black American adolescent cohort including both normotensive
      and prehypertensive participants with and without obesity. Measurements of BP,
      body mass index (BMI), plasma c-terminal FGF23, and echocardiographic measures of
      left ventricular mass index (LVMI) were obtained in 236 adolescents, aged 13-18
      years, stratified by BMI as normal, overweight, or obese. LVMI differed
      significantly between normal, overweight, and obese groups (30.42 +/- 6.75 vs.
      33.49 +/- 8.65 vs. 37.26 +/- 6.99 gm/m2.7; P < .01). FGF23 was significantly
      higher in both overweight (53.03 RU/mL) and obese (54.40 RU/mL) compared to the
      normal weight (32.83 RU/mL) group (both P < .01). In multiple linear regression
      analysis, variables significantly related to LVMI in males were BMI (P < .0001)
      and FGF23 (P = .005), but not BP, high-sensitivity C-reactive protein, or
      insulin. The only significant variable associated with LVMI in females was BMI (P
      < .0001). In males, the contribution of FGF23 to predicting LVMI was independent
      of and in addition to obesity. These results suggest that FGF23 is an integral
      part of a complex pathway, associated with higher cardiac mass in African
      Americans males with excess adiposity.

PMID- 28456499
TI  - [Use of resources and costs associated with non-adherence to inhaled
      corticosteroid treatment in asthma].
AB  - OBJECTIVE: To estimate adherence to asthma treatment with inhaled corticosteroid
      in clinical daily practice, and its relationship with exacerbations, as well as
      its use of resources and costs. MATERIAL AND METHODS: An observational,
      retrospective study using the electronic medical records of the Badalona Health
      Service provider. The study included patients>=15 years old with a confirmed
      diagnosed of asthma, and who initiated treatment with an inhaled corticosteroid
      between January 2010 and December 2011. The follow-up period was 24 months.
      Adherence to treatment was measured using the medication possession ratio. Two
      groups were established: adherent (ADH; medication possession ratio>=80%) and non
      adherent (non-ADH; medication possession ratio<80%) patients. The main
      demographic and clinical variables, including exacerbations, were collected,
      along with the healthcare and non-healthcare (days of absence from work) resource
      use, and costs. RESULTS: The study included a total of 2,303 patients, with a
      mean age of 48.6 years, and 64.3% females. Just over half (52.6%) of the patients
      had moderate persistent asthma, and 51.0% of patients adhered to treatment. In
      the non-ADH patients, 63.4% suffered at least one exacerbation in the follow-up
      period, compared with 37.4% of the adherent patients (P<.001). The non-ADH
      patients also consumed a higher percentage of healthcare resources in Primary
      Care (22.5 vs. 17.4%), secondary care (3.3 vs. 2.5%), and emergency visits (1.4
      vs. 0.2%) during the follow-up period (P<.001 in all cases). No statistical
      significance differences were observed in the days of absence from work. Mean
      annual cost of non-ADH patients was 1,431?/patient, compared with 722?/patient
      (P<.001) of ADH patients. CONCLUSION: Lack of adherence was associated with an
      increase in exacerbation rates, as well as healthcare resource consumption and
      costs.

PMID- 28456500
TI  - Epitheloid hemangioendothelioma of the ankle with unusual magnetic resonance
      imaging appearance.

PMID- 28456502
TI  - Drinking-reduction goals offer potential to widen the options for measuring and
      treating alcohol dependence.

PMID- 28456501
TI  - Change in non-abstinent WHO drinking risk levels and alcohol dependence: a 3 year
      follow-up study in the US general population.
AB  - BACKGROUND: Alcohol dependence is often untreated. Although abstinence is often
      the aim of treatment, many drinkers prefer drinking reduction goals. Therefore,
      if supported by evidence of benefit, drinking reduction goals could broaden the
      appeal of treatment. Regulatory agencies are considering non-abstinent outcomes
      as efficacy indicators in clinical trials, including reduction in WHO drinking
      risk levels-very high, high, moderate, and low-defined in terms of mean ethanol
      consumption (in grams) per day. We aimed to study the relationship between
      reductions in WHO drinking risk levels and subsequent reduction in the risk of
      alcohol dependence. METHODS: In this population-based cohort study, we included
      data from 22 005 drinkers who were interviewed in 2001-02 (Wave 1) and re
      interviewed 3 years later (2004-05; Wave 2) in the US National Epidemiologic
      Survey on Alcohol and Related Conditions. Alcohol consumption (WHO drinking risk
      levels) and alcohol dependence (at least three of seven DSM-IV criteria in the
      previous 12 months) were assessed at both waves. We used logistic regression to
      test the relationship between change in WHO drinking risk levels between Waves 1
      and 2, and alcohol dependence at Wave 2. FINDINGS: At Wave 1, 2.5% (weighted
      proportion) of the respondents were very-high-risk drinkers, 2.5% were high-risk
      drinkers, 4.8% were moderate-risk drinkers, and most (90.2%) were low-risk
      drinkers. Reduction in WHO drinking risk level predicted significantly lower odds
      of alcohol dependence at Wave 2, particularly among very-high-risk drinkers
      (adjusted odds ratios 0.27 [95% CI 0.18-0.41] for reduction by one level, 0.17
      [0.10-0.27] for two levels, and 0.07 [0.05-0.10] for three levels) and high-risk
      drinkers (0.64 [0.54-0.75] for one level and 0.12 [0.09-0.15] for two levels),
      and among those with alcohol dependence at Wave 1 (0.29 [0.15-0.57] for one
      level, 0.06 [0.04-0.10] for two levels, and 0.04 [0.03-0.06] for three levels in
      very-high-risk drinkers). INTERPRETATION: Our results support the use of
      reductions in WHO drinking risk levels as an efficacy outcome in clinical trials.
      Because these risk levels can be readily translated into standard drink
      equivalents per day of different countries, the WHO risk levels could also be
      used internationally to guide treatment goals and clinical recommendations on
      drinking reduction. FUNDING: US National Institute on Alcohol Abuse and
      Alcoholism, New York State Psychiatric Institute, the Alcohol Clinical Trials
      Initiative.

PMID- 28456504
TI  - Diagnosis of Cardiac Amyloidosis: Is Imaging Enough?

PMID- 28456503
TI  - Novel oxytocin receptor variants in laboring women requiring high doses of
      oxytocin.
AB  - BACKGROUND: Although oxytocin commonly is used to augment or induce labor, it is
      difficult to predict its effectiveness because oxytocin dose requirements vary
      significantly among women. One possibility is that women requiring high or low
      doses of oxytocin have variations in the oxytocin receptor gene. OBJECTIVES: To
      identify oxytocin receptor gene variants in laboring women with low and high
      oxytocin dosage requirements. STUDY DESIGN: Term, nulliparous women requiring
      oxytocin doses of <=4 mU/min (low-dose-requiring, n = 83) or >=20 mU/min (high
      dose-requiring, n = 104) for labor augmentation or induction provided consent to
      a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing
      (coverage >30*) with MiSeq (Illumina) was performed to discover variants in the
      coding exons of the oxytocin receptor gene. Baseline relevant clinical history,
      outcomes, demographics, and oxytocin receptor gene sequence variants and their
      allele frequencies were compared between low-dose-requiring and high-dose
      requiring women. The Scale-Invariant Feature Transform algorithm was used to
      predict the effect of variants on oxytocin receptor function. The Fisher exact or
      chi2 tests were used for categorical variables, and Student t tests or Wilcoxon
      rank sum tests were used for continuous variables. A P value < .05 was considered
      statistically significant. RESULTS: The high-dose-requiring women had greater
      rates of obesity and diabetes and were more likely to have undergone labor
      induction and required prostaglandins. High-dose-requiring women were more likely
      to undergo cesarean delivery for first-stage arrest and less likely to undergo
      cesarean delivery for nonreassuring fetal status. Targeted sequencing of the
      oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding
      variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One
      novel variant (A243T) was found in both the low- and high-dose-requiring groups.
      Three novel variants (Y106H, A240_A249del, and P197delfs*206) resulting in an
      amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation,
      respectively, were identified only in low-dose-requiring women. Nine
      nonsynonymous variants were unique to the high-dose-requiring group. These
      included 3 known variants (R151C, G221S, and W228C) and 6 novel variants (M133V,
      R150L, H173R, A248V, G253R, and I266V). Of these, R150L, R151C, and H173R were
      predicted by Scale-Invariant Feature Transform algorithm to damage oxytocin
      receptor function. There was no statistically significant association between the
      numbers of synonymous and nonsynonymous substitutions in the patient groups.
      CONCLUSION: Obesity, diabetes, and labor induction were associated with the
      requirement for high doses of oxytocin. We did not identify significant
      differences in the prevalence of oxytocin receptor variants between low-dose
      requiring and high-dose-requiring women, but novel oxytocin receptor variants
      were enriched in the high-dose-requiring women. We also found 3 oxytocin receptor
      variants (2 novel, 1 known) that were predicted to damage oxytocin receptor
      function and would likely increase an individual's risk for requiring a high
      oxytocin dose. Further investigation of oxytocin receptor variants and their
      effects on protein function will inform precision medicine in pregnant women.

PMID- 28456505
TI  - Electrocardiographic Markers of Sudden Death: More Frequent Than Suspected.

PMID- 28456506
TI  - Role of Ivabradine in the Treatment of Heart Failure: Comments on the ESC 2016
      Guidelines.

PMID- 28456507
TI  - WOMAN: reducing maternal deaths with tranexamic acid.

PMID- 28456508
TI  - Universal health coverage, priority setting, and the human right to health.

PMID- 28456510
TI  - High acuity sleeve gastrectomy patients in a free-standing ambulatory surgical
      center.
AB  - BACKGROUND: Procedures performed in ambulatory surgical centers (ASC) can provide
      several advantages over hospital-based surgery. Understandably, concerns have
      been raised regarding "high acuity" cases in the ASC setting. Recently the
      Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program
      (MBSAQIP) presented protocols for ASCs to follow, requiring them to perform only
      "low acuity" cases to be compliant with accreditation. OBJECTIVE: Assess the
      safety and efficacy of outpatient sleeve gastrectomy (SG) on the "high acuity
      patient" in a free-standing ASC. SETTING: Free-standing ASC, Eviva Bariatrics,
      Seattle, Washington. METHODS: Data were collected retrospectively for all
      patients who underwent sleeve gastrectomy from January 1, 2013 to December 31,
      2015, n = 1112. Of those patients, 120 were classified as "high acuity." RESULTS:
      Mean age was 51.7 years (24-73), mean body mass index was 42.4 (26.2-65.9). Mean
      operative time was 91 minutes. Five patients (4.2%) were readmitted within 30
      days. Causes of re-admission were portal vein thrombosis (n = 2), intra-abdominal
      abscess (n = 1), infected hematoma (n = 1), and postoperative bleeding (n = 1).
      One patient (0.83%) was transferred from the ASC to a nearby hospital due to a
      postoperative bleed. One patient (0.83%) had a re-operation to evacuate a
      hematoma. One patient had a re-operation to wash out an infected hematoma. There
      were 0 confirmed staple line leaks. There were no open conversions and no deaths
      within 30 days or at 1 year. Follow-up was 83% (n = 100) at 6 months, and 65.0%
      at 1 year (n = 78). CONCLUSION: Criteria such as age, body mass index, or prior
      bariatric surgery did not reflect worse outcomes in a specialized ASC. With
      experienced surgeons, appropriate protocols, and a consistent operative team, SG
      can be performed safely in a free-standing ASC on select "high acuity" patients.

PMID- 28456511
TI  - Different effects of bariatric surgical procedures on dyslipidemia: a registry
      based analysis.
AB  - BACKGROUND: The scale and variables linked to bariatric surgery's effect on
      dyslipidemia have not been conclusive. OBJECTIVE: To compare the effect of Roux
      en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric
      banding (LAGB) on dyslipidemia SETTING: National bariatric surgery registry.
      METHODS: Plasma lipids and associated variables were compared at baseline and 1
      year (12+/-4 mo) after surgery for registry patients with dyslipidemia enrolled
      from June 2013 to August 2014. RESULTS: The greatest mean total-cholesterol (TC)
      reduction was observed post-RYGB, 226.7+/-26.4 to 181.3+/-30.9 mg/dL (19.9%, n =
      208), followed by post-SG, 227.9+/-24.4 to 206.7+/-34.2 mg/dL (8.9%, n = 1515;
      P<.001). Normal TC levels of below 200 mg/dL were achieved by 76% post-RYGB
      patients compared with 43.5% post-SG patients (odds ratio [OR] = 6.24, 95%
      confidence interval [CI]: 3.69-10.53) and 25.6% post-LABG patients (OR = 9.66,
      95% CI: 4.11-22.67; P<.01). Although equivalent patterns were observed for low
      density-lipoprotein cholesterol (LDL), the levels of high-density-lipoprotein
      cholesterol (HDL) were most improved post-SG, reaching normal levels in 58.1% of
      SG male patients versus 39.5% of RYGB male patients (OR = 1.56, 95% CI: 1.04
      2.35), (P = .02). The lowering of triglyceride levels by approximately 75% was
      comparable after SG and RYGB procedures. The type of surgery was the strongest
      independent predictor for all lipid level improvements or remissions. Male sex
      was an independent predictor for LDL normalization only (OR = 1.88, 95% CI: 1.24
      2.85). Excess weight loss offered no meaningful prediction for lipid improvement
      (OR = 1.01-1.03). CONCLUSION: Particular types of bariatric surgeries had
      different effects on dyslipidemia, independent of weight loss. Overall, the RYGB
      achieved the biggest reduction in plasma lipids (TC and LDL), although SG did
      affect HDL. Our results could aid in the decision-making process regarding the
      most appropriate procedure for patients with dyslipidemia.

PMID- 28456512
TI  - Inter-labeler and intra-labeler variability of condition severity classification
      models using active and passive learning methods.
AB  - BACKGROUND AND OBJECTIVES: Labeling instances by domain experts for
      classification is often time consuming and expensive. To reduce such labeling
      efforts, we had proposed the application of active learning (AL) methods,
      introduced our CAESAR-ALE framework for classifying the severity of clinical
      conditions, and shown its significant reduction of labeling efforts. The use of
      any of three AL methods (one well known [SVM-Margin], and two that we introduced
      [Exploitation and Combination_XA]) significantly reduced (by 48% to 64%)
      condition labeling efforts, compared to standard passive (random instance
      selection) SVM learning. Furthermore, our new AL methods achieved maximal
      accuracy using 12% fewer labeled cases than the SVM-Margin AL method. However,
      because labelers have varying levels of expertise, a major issue associated with
      learning methods, and AL methods in particular, is how to best to use the
      labeling provided by a committee of labelers. First, we wanted to know, based on
      the labelers' learning curves, whether using AL methods (versus standard passive
      learning methods) has an effect on the Intra-labeler variability (within the
      learning curve of each labeler) and inter-labeler variability (among the learning
      curves of different labelers). Then, we wanted to examine the effect of learning
      (either passively or actively) from the labels created by the majority consensus
      of a group of labelers. METHODS: We used our CAESAR-ALE framework for classifying
      the severity of clinical conditions, the three AL methods and the passive
      learning method, as mentioned above, to induce the classifications models. We
      used a dataset of 516 clinical conditions and their severity labeling,
      represented by features aggregated from the medical records of 1.9 million
      patients treated at Columbia University Medical Center. We analyzed the variance
      of the classification performance within (intra-labeler), and especially among
      (inter-labeler) the classification models that were induced by using the labels
      provided by seven labelers. We also compared the performance of the passive and
      active learning models when using the consensus label. RESULTS: The AL methods:
      produced, for the models induced from each labeler, smoother Intra-labeler
      learning curves during the training phase, compared to the models produced when
      using the passive learning method. The mean standard deviation of the learning
      curves of the three AL methods over all labelers (mean: 0.0379; range: [0.0182 to
      0.0496]), was significantly lower (p=0.049) than the Intra-labeler standard
      deviation when using the passive learning method (mean: 0.0484; range: [0.0275
      0.0724). Using the AL methods resulted in a lower mean Inter-labeler AUC standard
      deviation among the AUC values of the labelers' different models during the
      training phase, compared to the variance of the induced models' AUC values when
      using passive learning. The Inter-labeler AUC standard deviation, using the
      passive learning method (0.039), was almost twice as high as the Inter-labeler
      standard deviation using our two new AL methods (0.02 and 0.019, respectively).
      The SVM-Margin AL method resulted in an Inter-labeler standard deviation (0.029)
      that was higher by almost 50% than that of our two AL methods The difference in
      the inter-labeler standard deviation between the passive learning method and the
      SVM-Margin learning method was significant (p=0.042). The difference between the
      SVM-Margin and Exploitation method was insignificant (p=0.29), as was the
      difference between the Combination_XA and Exploitation methods (p=0.67). Finally,
      using the consensus label led to a learning curve that had a higher mean intra
      labeler variance, but resulted eventually in an AUC that was at least as high as
      the AUC achieved using the gold standard label and that was always higher than
      the expected mean AUC of a randomly selected labeler, regardless of the choice of
      learning method (including a passive learning method). Using a paired t-test, the
      difference between the intra-labeler AUC standard deviation when using the
      consensus label, versus that value when using the other two labeling strategies,
      was significant only when using the passive learning method (p=0.014), but not
      when using any of the three AL methods. CONCLUSIONS: The use of AL methods, (a)
      reduces intra-labeler variability in the performance of the induced models during
      the training phase, and thus reduces the risk of halting the process at a local
      minimum that is significantly different in performance from the rest of the
      learned models; and (b) reduces Inter-labeler performance variance, and thus
      reduces the dependence on the use of a particular labeler. In addition, the use
      of a consensus label, agreed upon by a rather uneven group of labelers, might be
      at least as good as using the gold standard labeler, who might not be available,
      and certainly better than randomly selecting one of the group's individual
      labelers. Finally, using the AL methods: when provided by the consensus label
      reduced the intra-labeler AUC variance during the learning phase, compared to
      using passive learning.

PMID- 28456513
TI  - Lifestyle interventions based on the diabetes prevention program delivered via
      eHealth: A systematic review and meta-analysis.
AB  - The objective was to describe Diabetes Prevention Program (DPP)-based lifestyle
      interventions delivered via electronic, mobile, and certain types of telehealth
      (eHealth) and estimate the magnitude of the effect on weight loss. A systematic
      review was conducted. PubMed and EMBASE were searched for studies published
      between January 2003 and February 2016 that met inclusion and exclusion criteria.
      An overall estimate of the effect on mean percentage weight loss across all the
      interventions was initially conducted. A stratified meta-analysis was also
      conducted to determine estimates of the effect across the interventions
      classified according to whether behavioral support by counselors post-baseline
      was not provided, provided remotely with communication technology, or face-to
      face. Twenty-two studies met the inclusion/exclusion criteria, in which 26
      interventions were evaluated. Samples were primarily white and college educated.
      Interventions included Web-based applications, mobile phone applications, text
      messages, DVDs, interactive voice response telephone calls, telehealth video
      conferencing, and video on-demand programing. Nine interventions were stand
      alone, delivered post-baseline exclusively via eHealth. Seventeen interventions
      included additional behavioral support provided by counselors post-baseline
      remotely with communication technology or face-to-face. The estimated overall
      effect on mean percentage weight loss from baseline to up to 15months of follow
      up across all the interventions was -3.98%. The subtotal estimate across the
      stand-alone eHealth interventions (-3.34%) was less than the estimate across
      interventions with behavioral support given by a counselor remotely (-4.31%), and
      the estimate across interventions with behavioral support given by a counselor in
      person (-4.65%). There is promising evidence of the efficacy of DPP-based eHealth
      interventions on weight loss. Further studies are needed particularly in racially
      and ethnically diverse populations with limited levels of educational attainment.
      Future research should also focus on ways to optimize behavioral support.

PMID- 28456514
TI  - Respiratory distress in term neonates in low-resource settings.
AB  - Most neonatal deaths worldwide occur in low- and middle-income countries (LMICs).
      Respiratory distress is an important cause of neonatal morbidity and mortality.
      The epidemiology of respiratory distress among term neonates who constitute the
      vast majority of births is under reported. The scarcely available data from LMICs
      suggest an incidence of 1.2% to 7.2% among term live births and greater morbidity
      compared to that in high-income countries. Pneumonia and meconium aspiration
      syndrome are the predominant causes among outborn neonates, but next only to
      transient tachypnea among inborn neonates. Community management of neonatal
      sepsis/pneumonia using simplified antibiotic regimens when referral is not
      feasible, implementation of non-invasive ventilation, and innovative low-cost
      technologies to deliver respiratory therapy are important advances that have
      taken place in these settings. There is an urgent need to generate data on
      respiratory morbidities among term neonates so that the limited resources in
      these settings can be allocated judiciously.

PMID- 28456515
TI  - Spatial encryption of G protein-coupled receptor signaling in endosomes;
      Mechanisms and applications.
AB  - Within any cellular signaling system membrane trafficking is a critical mechanism
      for cells to translate complex networks into specific downstream responses,
      including the signal pathways activated by the superfamily of G protein-coupled
      receptors (GPCRs). Classically, membrane trafficking is viewed as a mechanism to
      regulate ligand sensitivity of a target tissue by controlling the level of
      surface receptors. Recent studies, however, have not only highlighted that GPCR
      trafficking is a tightly regulated process critical for spatio-temporal control
      of signaling, but that heterotrimeric G protein signaling can also be reactivated
      or continue to signal from distinct endocytic compartments, and even endosomal
      microdomains. The significance of spatio-temporal control will be discussed, not
      only with respect to how these novel molecular pathways impact our basic
      understanding of cellular regulation, but also our view of how aberrant signaling
      can result in disease. Furthermore, these mechanisms offer the potential
      application for novel therapeutic strategies to identify GPCR compounds with high
      specificity in their actions.

PMID- 28456516
TI  - Identification of novel 1-indolyl acetate-5-nitroimidazole derivatives of
      combretastatin A-4 as potential tubulin polymerization inhibitors.
AB  - Microtubules are essential for the mitotic division of cells and have become an
      attractive target for anti-tumour drugs due to the increased incidence of cancer
      and significant mitosis rate of tumour cells. In this study, a total of six
      indole 1-position modified 1-indolyl acetate-5-nitroimidazole derivatives were
      designed, synthesized, and evaluated for their ability to inhibit tubulin
      polymerization caused by binding to the colchicine-binding site of tubulin. Among
      them, compound 3 displayed the best ability to inhibit tubulin polymerization; it
      also exhibited better anti-proliferative activities than colchicine against a
      panel of human cancer cells (with IC50 values ranging from 15 to 40nM),
      especially HeLa cells (with IC50 values of 15nM), based on the cellular
      cytotoxicity assay results. Moreover, cellular mechanism studies indicated that
      compound 3 could induce G2/M phase arrest and apoptosis of HeLa and MCF-7 cells,
      which were associated with alterations in the expression of cell cycle-checkpoint
      related proteins (Cyclin B1, Cdc2, and P21) and a reduction in the mitochondrial
      membrane potential as well as alterations in the levels of apoptosis-related
      proteins (PARP, Caspase 9, Bcl-2, and Bax) of these cells, respectively.
      Importantly, in vivo studies further revealed that compound 3 could dramatically
      suppress HeLa cell xenograft tumour growth compared with vehicle and CA-4
      phosphate (CA-4P), and no signs of toxicity were observed in these mice.
      Collectively, these in vitro and in vivo results indicated that compound 3 might
      be a promising lead compound for further development as a potential anti-cancer
      drug.

PMID- 28456518
TI  - Vaginal ecosystem modeling of growth patterns of anaerobic bacteria in
      microaerophilic conditions.
AB  - The human vagina constitutes a complex ecosystem created through relationships
      established between host mucosa and bacterial communities. In this ecosystem,
      classically defined bacterial aerobes and anaerobes thrive as communities in the
      microaerophilic environment. Levels of CO2 and O2 present in the vaginal lumen
      are impacted by both the ecosystem's physiology and the behavior and health of
      the human host. Study of such complex relationships requires controlled and
      reproducible causational approaches that are not possible in the human host that,
      until recently, was the only place these bacterial communities thrived. To
      address this need we have utilized our ex vivo human vaginal mucosa culture
      system to support controlled, reproducible colonization by vaginal bacterial
      communities (VBC) collected from healthy, asymptomatic donors. Parallel vaginal
      epithelial cells (VEC)-VBC co-cultures were exposed to two different atmospheric
      conditions to study the impact of CO2 concentrations upon the anaerobic bacteria
      associated with dysbiosis and inflammation. Our data suggest that in the context
      of transplanted VBC, increased CO2 favored specific lactobacilli species defined
      as microaerophiles when grown as monocultures. In preliminary studies, the
      observed community changes also led to shifts in host VEC phenotypes with
      significant changes in the host transcriptome, including altered expression of
      select molecular transporter genes. These findings support the need for
      additional study of the environmental changes associated with behavior and health
      upon the symbiotic and adversarial relationships that are formed in microbial
      communities present in the human vaginal ecosystem.

PMID- 28456517
TI  - Proprotein convertase inhibition: Paralyzing the cell's master switches.
AB  - Proprotein convertases are serine proteases responsible for the cleavage and
      subsequent activation of protein substrates, many of them relevant for the
      development of an ample variety of diseases. Seven of the PCs, including furin
      and PACE4, recognize and hydrolyze the C-terminal end of the general sequence
      RXRR/KXR, whereas PCSK-9 recognizes a series of non-basic amino acids. In some
      systems, PC-mediated substrate activation results in the development of
      pathological processes, such as cancer, endocrinopathies, and cardiovascular and
      infectious diseases. After establishing PCs as relevant contributors to disease
      processes, research efforts were directed towards the development of inhibition
      strategies, including small and large molecules, anti-sense therapies, and
      antibody-based therapies. Most of these inhibitors mimic the consensus sequence
      of PCs, blocking the active site in a competitive manner. The most promising
      inhibitors were designed as bioengineered proteins; however, some non-protein and
      peptidomimetic agents have also proved to be effective. These efforts led to the
      design of pre-clinical studies and clinical trials utilizing inhibitors to PCs.
      Although the initial studies were performed using non-selective PCs inhibitors,
      such as CMK, the search for more specific, and compartmentalized selective
      inhibitors resulted in specific activities ascribed to some, but not all of the
      PCs. For instance, PACE4 inhibitors were effective in decreasing prostate cancer
      cell proliferation, and neovascularization. Decreased metastatic ovarian cancer
      utilizing furin inhibitors represents one of the major endeavors, currently in a
      phase II trial stage. Antibodies targeting PCSK-9 decreased significantly the
      levels of HDL-cholesterol, in a phase III trial. The study of Proprotein
      convertases has reached a stage of maturity. New strategies based on the
      alteration of their activity at the cellular and clinical level represent a
      promising experimental pharmacology field. The development of allosteric
      inhibitors, or specific agents directed against individual PCs is one of the
      challenges to be unraveled in the future.

PMID- 28456520
TI  - Complete Blood Count or Complete Blood Count with Differential: What's the
      Difference?

PMID- 28456509
TI  - Effect of early tranexamic acid administration on mortality, hysterectomy, and
      other morbidities in women with post-partum haemorrhage (WOMAN): an
      international, randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Post-partum haemorrhage is the leading cause of maternal death
      worldwide. Early administration of tranexamic acid reduces deaths due to bleeding
      in trauma patients. We aimed to assess the effects of early administration of
      tranexamic acid on death, hysterectomy, and other relevant outcomes in women with
      post-partum haemorrhage. METHODS: In this randomised, double-blind, placebo
      controlled trial, we recruited women aged 16 years and older with a clinical
      diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section
      from 193 hospitals in 21 countries. We randomly assigned women to receive either
      1 g intravenous tranexamic acid or matching placebo in addition to usual care. If
      bleeding continued after 30 min, or stopped and restarted within 24 h of the
      first dose, a second dose of 1 g of tranexamic acid or placebo could be given.
      Patients were assigned by selection of a numbered treatment pack from a box
      containing eight numbered packs that were identical apart from the pack number.
      Participants, care givers, and those assessing outcomes were masked to
      allocation. We originally planned to enrol 15 000 women with a composite primary
      endpoint of death from all-causes or hysterectomy within 42 days of giving birth.
      However, during the trial it became apparent that the decision to conduct a
      hysterectomy was often made at the same time as randomisation. Although
      tranexamic acid could influence the risk of death in these cases, it could not
      affect the risk of hysterectomy. We therefore increased the sample size from 15
      000 to 20 000 women in order to estimate the effect of tranexamic acid on the
      risk of death from post-partum haemorrhage. All analyses were done on an
      intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8,
      2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.
      FINDINGS: Between March, 2010, and April, 2016, 20 060 women were enrolled and
      randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of
      whom 10 036 and 9985, respectively, were included in the analysis. Death due to
      bleeding was significantly reduced in women given tranexamic acid (155 [1.5%] of
      10 036 patients vs 191 [1.9%] of 9985 in the placebo group, risk ratio [RR] 0.81,
      95% CI 0.65-1.00; p=0.045), especially in women given treatment within 3 h of
      giving birth (89 [1.2%] in the tranexamic acid group vs 127 [1.7%] in the placebo
      group, RR 0.69, 95% CI 0.52-0.91; p=0.008). All other causes of death did not
      differ significantly by group. Hysterectomy was not reduced with tranexamic acid
      (358 [3.6%] patients in the tranexamic acid group vs 351 [3.5%] in the placebo
      group, RR 1.02, 95% CI 0.88-1.07; p=0.84). The composite primary endpoint of
      death from all causes or hysterectomy was not reduced with tranexamic acid (534
      [5.3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5.5%] in the
      placebo group, RR 0.97, 95% CI 0.87-1.09; p=0.65). Adverse events (including
      thromboembolic events) did not differ significantly in the tranexamic acid versus
      placebo group. INTERPRETATION: Tranexamic acid reduces death due to bleeding in
      women with post-partum haemorrhage with no adverse effects. When used as a
      treatment for postpartum haemorrhage, tranexamic acid should be given as soon as
      possible after bleeding onset. FUNDING: London School of Hygiene & Tropical
      Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda
      Gates Foundation.

PMID- 28456519
TI  - Treatment of Hepatitis C virus infection in Italy: A consensus report from an
      expert panel.
AB  - Hepatitis C virus (HCV) infection remains one of the main causes of chronic liver
      disease worldwide. The advent of direct-acting antivirals (DAAs) has
      significantly improved the course of patients with chronic HCV infection (CHC),
      due to the ability of these drugs to achieve high rates of sustained virological
      response (SVR). These exceedingly high rates of SVR and the excellent safety data
      have been confirmed in real life practice. Evolving guidelines have been issued
      by national and international scientific societies in accordance with the
      progression of clinical knowledge and the availability of new DAAs. These
      recommendations, however, may not be applied universally because of delays in
      drugs reimbursability in different countries and because some National Health
      Systems identify only patients with advanced disease as a treatment priority.
      Italy in this regard is a prototype about DAAs treatment of CHC patients. With
      the aim to assess the Italian treatment experience with DAAs and to respond to
      unmet needs in treatment optimization of antiviral therapy in specific settings
      of CHC patients, a group of Italian experts met in Stresa in February 2017. The
      summary of the considerations arising from this two-day meeting and some
      statements regarding a few open issues are reported in this position paper.

PMID- 28456521
TI  - Visual integration enhances associative memory equally for young and older adults
      without reducing hippocampal encoding activation.
AB  - The ability to remember associations between previously unrelated pieces of
      information is often impaired in older adults (Naveh-Benjamin, 2000).
      Unitization, the process of creating a perceptually or semantically integrated
      representation that includes both items in an associative pair, attenuates age
      related associative deficits (Bastin et al., 2013; Ahmad et al., 2015; Zheng et
      al., 2015). Compared to non-unitized pairs, unitized pairs may rely less on
      hippocampally-mediated binding associated with recollection, and more on
      familiarity-based processes mediated by perirhinal cortex (PRC) and
      parahippocampal cortex (PHC). While unitization of verbal materials improves
      associative memory in older adults, less is known about the impact of visual
      integration. The present study determined whether visual integration improves
      associative memory in older adults by minimizing the need for hippocampal (HC)
      recruitment and shifting encoding to non-hippocampal medial temporal structures,
      such as the PRC and PHC. Young and older adults were presented with a series of
      objects paired with naturalistic scenes while undergoing fMRI scanning, and were
      later given an associative memory test. Visual integration was varied by
      presenting the object either next to the scene (Separated condition) or visually
      integrated within the scene (Combined condition). Visual integration improved
      associative memory among young and older adults to a similar degree by increasing
      the hit rate for intact pairs, but without increasing false alarms for recombined
      pairs, suggesting enhanced recollection rather than increased reliance on
      familiarity. Also contrary to expectations, visual integration resulted in
      increased hippocampal activation in both age groups, along with increases in PRC
      and PHC activation. Activation in all three MTL regions predicted discrimination
      performance during the Separated condition in young adults, while only a marginal
      relationship between PRC activation and performance was observed during the
      Combined condition. Older adults showed less overall activation in MTL regions
      compared to young adults, and associative memory performance was most strongly
      predicted by prefrontal, rather than MTL, activation. We suggest that visual
      integration benefits both young and older adults similarly, and provides a
      special case of unitization that may be mediated by recollective, rather than
      familiarity-based encoding processes.

PMID- 28456522
TI  - How handedness influences perceptual and attentional processes during rapid
      serial visual presentation.
AB  - Stimulus-driven orienting of visual attention is lateralized to the right
      hemisphere (RH). This lateralization has been studied in the dual-stream rapid
      serial visual presentation task (dual RSVP). In this task a second target (T2),
      hard to discern by being embedded in one of two lateral streams of rapidly
      changing distractors, is better identified on the left than on the right. This
      phenomenon is called the left visual field advantage (LVFA). Furthermore, in
      terms of event related potentials (ERPs), the N2pc component and visual evoked
      potentials (VEPs) are evoked earlier at the RH than at the left hemisphere (LH).
      All previous dual RSVP experiments were performed on right-handers. In the
      present study it was investigated how the LVFA and its neural correlates are
      modulated by handedness. To that end, the size of the LVFA and ERPs (VEPs and
      N2pc) were compared between right- and left-handers. VEPs were evoked earlier at
      the RH than the LH in right-handers but not in left-handers. Besides this effect,
      handedness modulated neither the size of the LVFA nor T2-evoked N2pc. Thus, the
      LVFA seems to be independent of handedness. Rather than for lateralization of
      attention, handedness might be relevant for lateralization of early visual
      perception processes.

PMID- 28456523
TI  - The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is
      Essential for snoRNA Biogenesis in Trypanosoma brucei.
AB  - The parasite Trypanosoma brucei is the causative agent of African sleeping
      sickness and is known for its unique RNA processing mechanisms that are common to
      all the kinetoplastidea including Leishmania and Trypanosoma cruzi. Trypanosomes
      possess two canonical RNA poly (A) polymerases (PAPs) termed PAP1 and PAP2. PAP1
      is encoded by one of the only two genes harboring cis-spliced introns in this
      organism, and its function is currently unknown. In trypanosomes, all mRNAs, and
      non-coding RNAs such as small nucleolar RNAs (snoRNAs) and long non-coding RNAs
      (lncRNAs), undergo trans-splicing and polyadenylation. Here, we show that the
      function of PAP1, which is located in the nucleus, is to polyadenylate non-coding
      RNAs, which undergo trans-splicing and polyadenylation. Major substrates of PAP1
      are the snoRNAs and lncRNAs. Under the silencing of either PAP1 or PAP2, the
      level of snoRNAs is reduced. The dual polyadenylation of snoRNA intermediates is
      carried out by both PAP2 and PAP1 and requires the factors essential for the
      polyadenylation of mRNAs. The dual polyadenylation of the precursor snoRNAs by
      PAPs may function to recruit the machinery essential for snoRNA processing.

PMID- 28456524
TI  - Protein Kinases in Pluripotency-Beyond the Usual Suspects.
AB  - Post-translational modification of proteins by phosphorylation plays a key role
      in regulating all aspects of eukaryotic biology. Embryonic stem cell (ESC)
      pluripotency, defined as the ability to differentiate into all cell types in the
      adult body, is no exception. Maintenance and dissolution of pluripotency are
      tightly controlled by phosphorylation. As a result, key signalling pathways that
      regulate pluripotency have been identified and their functions well
      characterised. Amongst the best studied are the fibroblast growth factor (FGF)
      ERK1/2 pathway, PI3K-AKT, the leukemia inhibitory factor (LIF)-JAK-STAT3 axis,
      Wnt-GSK3 signalling, and the transforming growth factor (TGF)beta family.
      However, these kinase pathways constitute only a small proportion of the protein
      kinase complement of pluripotent cells, and there is accumulating evidence that
      diverse phosphorylation systems modulate ESC pluripotency. Here, we review recent
      progress in understanding the overarching role of phosphorylation in mediating
      communication from the cellular environment, metabolism, and cell cycle to the
      core pluripotency machinery.

PMID- 28456525
TI  - Homologous and heterologous antigenic matched vaccines containing different H5
      hemagglutinins provide variable protection of chickens from the 2014 U.S. H5N8
      and H5N2 clade 2.3.4.4 highly pathogenic avian influenza viruses.
AB  - From December 2014 to June 2015, a novel H5 Eurasian A/goose/Guangdong (Gs/GD)
      lineage clade 2.3.4.4 high pathogenicity avian influenza (HPAI) virus caused the
      largest animal health emergency in US history resulting in mortality or culling
      of greater than 48 million poultry. The outbreak renewed interest in developing
      intervention strategies, including vaccines, for these newly emergent HPAI
      viruses. In these studies, several existing H5 vaccines or vaccine seed strains
      with varying genetic relatedness (85-100%) to the 2.3.4.4 HPAI viruses were
      evaluated for protection in poultry. Chickens received a single dose of either an
      inactivated whole H5 AI vaccine, or a recombinant fowl poxvirus or turkey
      herpesvirus-vectored vaccines with H5 AI hemagglutinin gene inserts followed by
      challenge with either a U.S. wild bird H5N8 (A/gyrfalcon/Washington/40188-6/2014)
      or H5N2 (A/northern pintail/Washington/40964/2014) clade 2.3.4.4 isolate. Results
      indicate that most inactivated H5 vaccines provided 100% protection from lethal
      effects of H5N8 or H5N2 challenge. In contrast, the recombinant live vectored
      vaccines only provided partial protection which ranged from 40 to 70%.
      Inactivated vaccine groups, in general, had lower number of birds shedding virus
      and at lower virus titers then the recombinant vaccine groups. Interestingly,
      prechallenge antibody titers using the HPAI challenge viruses as antigen in
      heterologous vaccine groups were typically low (<=2 log2), yet the majority of
      these birds survived challenge. Taken together, these studies suggest that
      existing vaccines when used in a single immunization strategy may not provide
      adequate protection in poultry against the 2.3.4.4 HPAI viruses. Updating the H5
      hemagglutinin to be genetically closer to the outbreak virus and/or using a prime
      boost strategy may be necessary for optimal protection.

PMID- 28456526
TI  - Strengthening and sustainability of national immunization technical advisory
      groups (NITAGs) globally: Lessons and recommendations from the founding meeting
      of the global NITAG network.
AB  - National Immunization Technical Advisory Groups (NITAGs) provide independent,
      evidence-informed advice to assist their governments in immunization policy
      formation. However, many NITAGs face challenges in fulfilling their roles. Hence
      the many requests for formation of a network linking NITAGs together so they can
      learn from each other. To address this request, the Health Policy and
      Institutional Development (HPID) Center (a WHO Collaborating Center at the Agence
      de Medecine Preventive - AMP), in collaboration with WHO, organized a meeting in
      Veyrier-du-Lac, France, on 11 and 12 May 2016, to establish a Global NITAG
      Network (GNN). The meeting focused on two areas: the requirements for (a) the
      establishment of a global NITAG collaborative network; and (b) the global
      assessment/evaluation of the performance of NITAGs. 35 participants from 26
      countries reviewed the proposed GNN framework documents and NITAG performance
      evaluation. Participants recommended that a GNN should be established, agreed on
      its governance, function, scope and a proposed work plan as well as setting a
      framework for NITAG evaluation.

PMID- 28456527
TI  - Patient reaction to Tdap vaccination in pregnancy.
AB  - BACKGROUND: The current obstetrical recommendation is to routinely administer the
      tetanus, diphtheria, and acellular pertussis (Tdap) vaccination during every
      pregnancy regardless of a patient's prior history. There are minimal data that
      have prospectively evaluated solicited patient response to this treatment plan.
      The study objective was to evaluate patient reaction following receipt of Tdap
      vaccination during pregnancy. METHODS: This was a prospective observational study
      conducted from May 2014 through March 2016. The study design involved solicited
      patient reaction within 1-7days after the administration of the Tdap vaccine.
      Data collected included pain or soreness, swelling, and/or redness at the
      injection site, as well as, fever and generalized body aches. Statistical
      analysis involved simple percentages with Poisson binomial 95% confidence
      intervals with Chi-square and Fisher's exact comparisons where appropriate.
      RESULTS: A total of 737 patients were evaluated and 496 (67%, 95% Confidence
      Interval [CI] 64-71%) were found to have at least 1 reaction to the vaccination
      and 187 (25%, 95% CI 22-29%) had 2 reactions or more. Overall, the majority of
      patients stated that the vaccination was tolerated. However, 24 (3%, 95% CI 2-5%)
      of the study population stated that they would not accept receipt of Tdap in a
      subsequent pregnancy because of the response that occurred in the current
      pregnancy. CONCLUSION: These data demonstrate that maternal reactions following
      receipt of Tdap are common (two-thirds of the study population). A potential
      concern is the finding that some patients might refuse a repeat vaccination in a
      subsequent pregnancy due to these reactions. If further research reveals similar
      findings, a pertussis only vaccine for pregnant patients might need to be
      evaluated.

PMID- 28456528
TI  - Evaluation of tandem Chlamydia trachomatis MOMP multi-epitopes vaccine in BALB/c
      mice model.
AB  - Chlamydia trachomatis (Ct), an obligate intracellular parasite, is the leading
      cause of bacterial sexually transmitted diseases worldwide. The best solution to
      control the spread of Ct is to develop safe and effective vaccines. However, an
      effective vaccine has not been developed due to some challenges such as selection
      of appropriate candidate antigens and an effective delivery system. In our
      previous study, we have developed a Ct vaccine that comprises a multi-epitope
      peptide of Ct major outer membrane protein (MOMP370-387) and Hepatitis B virus
      core antigen (HBcAg). The vaccine was evaluated in a murine model with chlamydial
      genital infection. The results indicated that Ct MOMP multi-epitope delivered by
      HBcAg could be an effective vaccine for the prevention of Ct. In this study,
      another two epitopes were selected from the MOMP protein and tandemly linked with
      MOMP370-387 to enhance the immunogenicity and the protective effect of the
      candidate vaccine. Our results revealed that both the immunogenicity and the
      protective effect of the tandem Ct MOMP multi-epitopes were much better than that
      of the single epitope. Therefore, vaccines based on the tandem Ct MOMP multi
      epitopes could be more effective immune prophylactics to prevent Ct infection
      than the single epitope in murine model system.

PMID- 28456529
TI  - Cost effectiveness of a targeted age-based West Nile virus vaccination program.
AB  - BACKGROUND: West Nile virus (WNV) is the leading cause of domestically-acquired
      arboviral disease in the United States. Several WNV vaccines are in various
      stages of development. We estimate the cost-effectiveness of WNV vaccination
      programs targeting groups at increased risk for severe WNV disease. METHODS: We
      used a mathematical model to estimate costs and health outcomes of vaccination
      with WNV vaccine compared to no vaccination among seven cohorts, spaced at 10year
      intervals from ages 10 to 70years, each followed until 90-years-old. U.S.
      surveillance data were used to estimate WNV neuroinvasive disease incidence. Data
      for WNV seroprevalence, acute and long-term care costs of WNV disease patients,
      quality-adjusted life-years (QALYs), and vaccine characteristics were obtained
      from published reports. We assumed vaccine efficacy to either last lifelong or
      for 10years with booster doses given every 10years. RESULTS: There was a
      statistically significant difference in cost-effectiveness ratios across cohorts
      in both models and all outcomes assessed (Kruskal-Wallis test p<0.0001). The 60
      year-cohort had a mean cost per neuroinvasive disease case prevented of $664,000
      and disability averted of $1,421,000 in lifelong model and $882,000 and
      $1,887,000, respectively in 10-year immunity model; these costs were
      statistically significantly lower than costs for other cohorts (p<0.0001).
      Vaccinating 70-year-olds had the lowest cost per death averted in both models at
      around $4.7 million (95%CI $2-$8 million). Cost per disease case averted was
      lowest among 40- and 50-year-old cohorts and cost per QALY saved lowest among 60
      year cohorts in lifelong immunity model. The models were most sensitive to
      disease incidence, vaccine cost, and proportion of persons developing disease
      among infected. CONCLUSIONS: Age-based WNV vaccination program targeting those at
      higher risk for severe disease is more cost-effective than universal vaccination.
      Annual variation in WNV disease incidence, QALY weights, and vaccine costs impact
      the cost effectiveness ratios.

PMID- 28456530
TI  - Influenza vaccine effectiveness against influenza-associated hospitalization in
      2015/16 season, Beijing, China.
AB  - BACKGROUND: Vaccination is recommended to prevent influenza virus infection and
      associated complications. This study aimed to estimate the influenza vaccine
      effectiveness (VE) against hospitalization in the 2015/16 season in Beijing.
      METHODS: Patients who were hospitalized in the 5 study hospitals between 1 Oct
      2015 and 15 May 2016 were recruited. Influenza vaccination status was obtained
      for PCR-confirmed influenza patients and the selected controls who tested
      negative for the virus. Conditional logistic regression was used to estimate the
      influenza VE matching by calendar week, and adjusting for age, study sites,
      underlying medical conditions, smoking status, and hospital admissions over the
      past 12months. RESULTS: The overall VE was -37.9% (95% CI: -103.3, 6.5) against
      laboratory-confirmed influenza-associated hospitalization. The 2015-16 seasonal
      vaccine was had -61.9% (95% CI: -211.9, 15.9), -5.4% (95% CI: -108.1, 46.6) and 
      45.2% (95% CI: -152.6, 16.5) effectiveness to prevent infection from
      A(H1N1)pdm09, A(H3N2) and influenza B, respectively. CONCLUSIONS: Influenza
      vaccination did not show effective protection against hospitalization with
      influenza in 2015/16 season in Beijing.

PMID- 28456532
TI  - An ecological framework for temporal and individual differences in color
      preferences.
AB  - There are well-known and extensive differences in color preferences between
      individuals, but there are also within-individual differences from one time to
      another. Despite the seeming independence between these individual and temporal
      effects, we propose that they have the same underlying cause: people's ecological
      experiences with color-associated objects and events. Our approach is motivated
      by the Ecological Valence Theory (EVT; Palmer & Schloss, 2010) which states that
      preference for a given color is determined by the combined valence
      (liking/disliking) of all objects and events associated with that color. We
      define three ecologically-based hypotheses for explaining temporal and individual
      differences in color preferences concerning: (1) differences in object valences,
      (2) differences in color-object associations, and (3) differences in object
      activations in the mind when preferences are measured. We review prior studies
      that support these hypotheses and raise open research questions about untested
      predictions. We also extend the computational framework of the EVT by defining a
      single weighted average equation that captures both individual and temporal
      differences in color preferences. Finally, we consider other factors that
      potentially contribute to color preferences, including abstract symbolic
      associations, color in design, and psychophysical and/or physiological factors.

PMID- 28456531
TI  - Rubella virus immunization status in preconception period among Chinese women of
      reproductive age: A nation-wide, cross-sectional study.
AB  - OBJECTIVE: Population-based studies on sero-epidemiology of Rubella in women
      before conception are lacking. The aim of this study was to investigate the sero
      prevalence of Rubella in a nationwide survey among Chinese women planning to get
      pregnant within six months. METHODS: This population-based, cross-sectional, sero
      survey of Rubella virus infection was a part of the National Free Preconception
      Health Examination Project covering all 31 provinces in Mainland China. Women
      intending to get pregnant within six months was enrolled between 2010 and 12.
      Information on demographic characteristics (age, residence status, race,
      education and occupation) and vaccination history was obtained by interviews.
      Rubella virus IgG sero-positivity was determined using venous blood samples.
      RESULTS: Of 2,120,131 women recruited to the study, Rubella virus IgG serology
      was available in 1,974,188 (99.3%). Participating women were of young age
      (median=28years), mostly engaged in agricultural activities (78%), and the
      majority (90%) had high school education or lower. The overall prevalence of
      Rubella virus IgG sero-positivity was 58.4% (1,161,129); geographical variation
      ranged from 92.5% in Jilin to 20.1% in Qinghai and 0.0% in Tibet. Only 4.6%
      (n=91,604) women reported to have had Rubella virus vaccination, and it varied
      from 18.6% (Guangdong) to 0.2% (Qinghai). Self-reported vaccination status did
      not correlate with Rubella virus IgG seropositivity. CONCLUSIONS: Prevalence of
      Rubella sero-positivity is low among Chinese women of reproductive age and there
      are significant regional differences. Over 40% of women being susceptible to
      Rubella in preconception period calls for a targeted screening and vaccination
      strategy.

PMID- 28456533
TI  - Paradoxical perception of object identity in visual motion.
AB  - In the course of perceptual organization, incomplete optical stimulation can
      evoke the experience of complete objects with distinct perceptual identities.
      According to a well-known principle of perceptual organization, stimulus parts
      separated by shorter spatial distances are more likely to appear as parts of the
      same perceptual identity. Whereas this principle of proximity has been confirmed
      in many studies of perceptual grouping in static displays, we show that it does
      not generalize to perception of object identity in dynamic displays, where the
      parts are separated by spatial and temporal distances. We use ambiguous displays
      which contain multiple moving parts and which can be perceived two ways: as two
      large objects that gradually change their size or as multiple smaller objects
      that rotate independent of one another. Grouping over long and short distances
      corresponds to the perception of the respectively large and small objects. We
      find that grouping over long distances is often preferred to grouping over short
      distances, against predictions of the proximity principle. Even though these
      effects are observed at high luminance contrast, we show that they are consistent
      with results obtained at the threshold of luminance contrast, in agreement with
      predictions of a theory of efficient motion measurement. This is evidence that
      the perception of object identity can be explained by a computational principle
      of neural economy rather than by the empirical principle of proximity.

PMID- 28456534
TI  - Analysis of facial morphology of UK and US general election candidates: Does the
      'power face' exist?
AB  - AIMS: To determine the frequency of recognised morphologic facial phenotypes
      among the UK and US election candidates and to assess whether there is a
      relationship between facial morphology and success in general elections. METHODS:
      Facial morphology analysis of prime ministerial and presidential candidates in
      the UK and US elections was performed. Direct facial measurements were made from
      frontal images and facial morphological indices calculated for all candidates.
      Anthropometric facial phenotype was determined and comparisons made between the
      elected leaders and unelected runner-up candidates. Paired candidates who had
      different facial types were analysed as a subgroup, with the probabilities of
      electoral success calculated. RESULTS: Data were available for 45 subjects: 22
      election winners and 23 unelected runner-ups. Our data showed some variation in
      facial morphology between the groups. The predominant facial phenotype in both
      groups was leptoprosopic (long and/or narrow face), accounting for 40% (n = 18).
      Mesoprosopic (average dimension) and euryprosopic (short and/or broad) facial
      type represented 31% (n = 14) and 18% (n = 8), respectively. A majority of the
      sample (n = 36) demonstrated a malar width to mandibular angle width ratio
      consistent with the modern 'power face' proportion. Subgroup analysis showed a
      significant association with success in an election when leptoprosopic candidates
      were paired against candidates of another facial phenotype (p < 0.05).
      CONCLUSION: Leptoprosopic (long and/or narrow) facial phenotype with a wide
      mandibular angle width is predominant in the UK and US election candidates.
      Moreover, this facial phenotype appears to be associated with greater electoral
      success, supporting the concept of a modern political 'power face'.

PMID- 28456535
TI  - "Dry bite" in venomous snakes: A review.
AB  - It is quite interesting that when a venomous snake bites a person and the victim
      does not suffer from any signs or symptoms of envenomation. A good percentage of
      venomous snake bites in humans do occur without venom injection. This phenomenon
      is termed as "Dry" bite in clinical medicine. Though this was not very uncommon
      in toxicological practice but, our awareness of this problem has increased. In
      this article an effort has been made to provide an insight into the incidence,
      pathophysiology and patho-mechanics of this unique medical enigma.

PMID- 28456536
TI  - Contribution of leukocytes to the induction and resolution of the acute
      inflammatory response in chickens.
AB  - A successful immune response against invading pathogens relies on the efficient
      activation of host defense mechanisms and a timely return to immune homeostasis.
      Despite their importance, these mechanisms remain ill-defined in most animal
      groups. This study focuses on the acute inflammatory response of chickens,
      important both as an avian model with a unique position in evolution as well as
      an increasingly notable target of infectious zoonotic diseases. We took advantage
      of an in vivo self-resolving intra-abdominal challenge model to provide an
      integrative view of leukocyte responses during the induction and resolution
      phases of acute inflammation. Our results showed rapid leukocyte infiltration
      into the abdominal cavity post zymosan challenge (significant increase as early
      as 4 h), which was dominated by heterophils. Peak leukocyte infiltration and ROS
      production reached maximum levels at 12 h post challenge, which was significantly
      earlier than comparative studies in teleost fish and mice. Both heterophils and
      monocyte/macrophages contributed to ROS production. Local leukocyte infiltration
      was preceded by an increase in peripheral leukocytes and a drop in the number of
      bone marrow leukocytes. The proportion of apoptotic leukocytes increased
      following peak of acute inflammation, rising to significant levels within the
      abdominal cavity by 48 h, consistent with other indicators for the resolution of
      inflammation. Importantly, comparison of chicken phagocytic responses with those
      previously shown in agnathan, teleost and murine models suggested a progressive
      evolutionary shift towards an increased sensitivity to pro-inflammatory pathogen
      derived particles and decreased sensitivity towards homeostatic stimuli. Thus,
      while significant conservation can be noted across the immune systems of
      endotherms, this study highlights additional unique features that govern the
      induction and resolution of acute inflammation in the avian system, which may be
      relevant to disease susceptibility and performance.

PMID- 28456537
TI  - Quality of life, functional impairment and social factors as determinants of
      nutritional status in older adults: The VERISAUDE study.
AB  - BACKGROUND & AIMS: Malnutrition is an important and growing health problem in
      elderly people. The main aim of this research was to examine the relationship
      between socio-demographic factors, social resources, functional status and
      quality of life and malnutrition or risk of malnutrition in elders. METHODS: A
      cross-sectional study was conducted with a representative sample of 749 community
      dwelling elders aged 65 years and over. A comprehensive assessment was carried
      out, including the collection of socio-demographic factors, social resources by
      the Older Americans Resources and Services Scale, nutritional status by the Mini
      Nutritional Assessment-Short Form, functional status by the Lawton's instrumental
      activities of daily living scale and quality of life by the World Health
      Organizations's Quality of Life measure-brief version (WHOQOL-BREF). RESULTS:
      Being female, the presence of totally impaired social resources and low scores in
      the physical health domain of the WHOQOL-BREF were the strongest determinants of
      malnutrition/risk of malnutrition. This model predicted 85.7% of the cases
      correctly. In men, the best determinants were being unmarried and having poor
      satisfaction with their health, with a percentage of 89.8% of cases of poor
      nutritional status correctly predicted. The best determinant for women was also
      the physical health domain of the WHOQOL-BREF, reaching a correct prediction of
      83.0% of malnutrition/risk of it. CONCLUSIONS: Nutritional status assessment and
      potential determinant factors should be incorporated as part of comprehensive
      assessments for early identification of malnutrition and to determine appropriate
      intervention strategies to address this public health problem in older adults.

PMID- 28456538
TI  - Plasma fatty acid patterns during pregnancy and child's growth, body composition,
      and cardiometabolic health: The Generation R Study.
AB  - BACKGROUND: Exposure to different concentrations of fatty acids during fetal life
      may affect growth and metabolism. However, most studies examined individual fatty
      acids, whereas concentrations highly correlate and may interact with each other.
      We aimed to evaluate patterns of plasma fatty acids during pregnancy and their
      associations with growth, body composition, and cardiometabolic health of the 6
      year-old offspring. METHODS: This study was performed in 4830 mother-child pairs
      participating in a population-based cohort in the Netherlands. Around 20 weeks of
      gestation, we measured plasma phospholipid concentrations of 22 fatty acids, in
      which we identified three fatty acid patterns using principal component analysis:
      a 'high n-6 polyunsaturated fatty acid (PUFA)' pattern, a 'monounsaturated and
      saturated fatty acid (MUFA and SFA)' pattern, and a 'high n-3 PUFA' pattern. When
      the children were 6 years old, we measured their anthropometrics and detailed
      body composition (using dual-energy X-ray absorptiometry), and we calculated
      their body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI). At
      the same age, children's blood pressure, and serum insulin, HDL-cholesterol, and
      triacylglycerol were measured. RESULTS: After adjustment for confounders and the
      other patterns, a higher score for the 'high n-6 PUFA' pattern during pregnancy
      was associated with a higher height, BMI, and FFMI in the offspring at 6 years,
      but not independently with cardiometabolic outcomes. The 'MUFA and SFA' pattern
      was not consistently associated with child body composition or cardiometabolic
      health. A higher score for the 'high n-3 PUFA' pattern was associated with a
      lower FMI, higher FFMI, higher HDL-cholesterol, and lower triacylglycerol.
      CONCLUSIONS: Our results suggest that plasma fatty acid patterns during pregnancy
      may affect offspring's body composition and cardiometabolic health. Specifically,
      a pattern characterized by high n-3 PUFA levels was associated with a more
      favorable body composition and blood lipid profile.

PMID- 28456540
TI  - AZFa Microdeletions: Occurrence in Chinese Infertile Men and Novel Deletions
      Revealed by Semiconductor Sequencing.
AB  - OBJECTIVE: To evaluate the frequency of azoospermia factor (AZFa) microdeletions
      among infertile men and establish a new high-throughput sequencing method to
      detect novel deletion types. MATERIALS AND METHODS: A total of 3731 infertile men
      were included. Karyotype analysis was performed using G-band staining of
      peripheral blood lymphocytes. Polymerase chain reaction (PCR) amplification using
      specific sequence-tagged sites (STS) was performed to screen for AZF region
      microdeletions of the Y chromosome. A novel semiconductor sequencing method was
      established to detect high-resolution AZFa microdeletions. RESULTS: Of 3731
      infertile men, 341 (9.14%) had microdeletions in AZFa, AZFb, or AZFc. Thirteen of
      these (3.81%) had a deletion in the AZFa region (mean age: 27.3 +/- 4 years,
      range: 22-34), which included 12 subjects with a normal karyotype (46, XY) and 1
      with Klinefelter syndrome (47, XXY). Four of 10 subjects with complete AZFa
      microdeletions (sY86 and sY84 loss) underwent semiconductor sequencing. They all
      had DNA sequence deletions from nt 14469266 to 15195932, whereas their fathers
      had no deletions. One subject with partial AZFa microdeletion (sY86 loss) and his
      father underwent semiconductor sequencing and STS-PCR analysis. The same deletion
      (sY86 loss with DNA sequence deletion from nt 14469266 to 14607672) was
      identified in both subjects. Forty sperm donators and 50 infertile men showed no
      AZFa microdeletions by either method. CONCLUSION: AZFa deletions are present at a
      low frequency in men with azoospermia or oligozoospermia. Novel sequencing
      methods can be used for these patients to reveal high-resolution AZFa
      microdeletions.

PMID- 28456539
TI  - Role of Preoperative Testicular Shear Wave Elastography in Predicting Improvement
      of Semen Parameters After Varicocelectomy for Male Patients With Primary
      Infertility.
AB  - OBJECTIVE: To evaluate the role of preoperative testicular shear wave
      elastography (SWE) in the prediction of improvement of semen analysis parameters
      after subinguinal microsurgical varicocele ligation in patients with primary
      infertility and clinically detectable varicocele. PATIENTS AND METHODS:
      Testicular SWE before the surgical intervention was done. Forty-eight patients
      were scheduled for subinguinal microsurgical varicocele ligation as a treatment
      option. Computer-assisted semen analysis was repeated 6 months after the
      intervention. RESULTS: At a cutoff value of 4.5 kPa, the stiffness index had a
      sensitivity of 86.4% and a specificity of 84.2% for semen parameter improvement
      after varicocelectomy. Correlation between different parameters of semen analysis
      and SWE showed a statistically significant negative correlation between SWE
      stiffness index and both sperm count (million/mL) and total motility. On the
      other hand, a nonsignificant negative correlation was found between SWE stiffness
      index and percentage of normal form. CONCLUSION: Testicular SWE is a good test
      that can be used in the assessment of male infertility with clinically detectable
      varicocele, and its results may predict semen parameter improvement after
      varicocelectomy. Further studies on a larger number of patients are needed to
      verify our results.

PMID- 28456541
TI  - Long-term Health-related Quality of Life Outcomes Following Radical Cystectomy.
AB  - OBJECTIVE: To evaluate the long-term (>5 years) health-related quality of life
      (HRQOL) outcomes following radical cystectomy, comparing Indiana pouch (IP),
      neobladder (NB), and ileal conduit (IC). MATERIALS AND METHODS: The departmental
      radical cystectomy database was queried to identify patients who underwent
      radical cystectomy and urinary diversion for bladder cancer between 1991 and 2009
      and had not died. Three hundred patients were identified and sent the validated
      Bladder Cancer Index instrument. RESULTS: A total of 128 (43%) patients completed
      the survey. When adjusted for gender, age at surgery, surgeon, and time since
      surgery, IC and IP patients had significantly better urinary function than NB
      patients (P = .0013). Sexual bother was less in NB than IP (P = .0387). Among men
      >=65 years of age, IC patients had significantly better urinary function (P =
      .0376) than NB patients (91.6 vs 49.4, respectively). Among men <65 years of age,
      IC and IP patients (76.0 and 82.8, respectively) had significantly better urinary
      function than NB patients (50.7) (P = .0199). Among women greater than 65 years,
      bowel bother was significantly better (P = .0095) for IC patients than IP
      patients (44.8 vs 69.5, respectively). CONCLUSION: Urinary diversion type after
      radical cystectomy affects HRQOL differently in long-term survivors. Age and
      gender at surgery influenced HRQOL based on diversion procedure. Urinary function
      but not urinary bother was significantly better in IC and IP compared to NB
      diversions. Prospective longitudinal studies using validated HRQOL tools will
      further help guide preoperative diversion choice decisions between patient and
      surgeon.

PMID- 28456542
TI  - Dietary Sodium Restriction Reduces Nocturnal Urine Volume and Nocturnal Polyuria
      Index in Renal Allograft Recipients With Nocturnal Polyuria.
AB  - OBJECTIVE: To investigate whether sodium restriction alters the nocturnal urine
      volume (NUV) and the ratio of NUV to 24-hour urine of renal allograft recipients
      (RARs). MATERIALS AND METHODS: This prospective, single-center study analyzed 38
      of the 59 RARs who were followed up for more than 6 months in our hospital. All
      patients underwent 3 sessions of dietary counseling performed by a board
      certified dietitian. Before and after these 3 sessions, 24-hour urine samples
      were collected, along with voiding frequency volume charts. RESULTS: Of the 38
      included RARs, 23 (60.5%) were diagnosed as having nocturnal polyuria (NP, NUV
      >10 mL/kg). After counseling the RARs with NP, their 24-hour sodium excretion was
      reduced from 169.5 to 125.6 mEq (P = .0066), their NUV from 862 to 709 mL (P =
      .021), and the ratio of NUV to 24-hour urine volume from 38.9% to 33.0% (P =
      .023). In contrast, these parameters were not significantly changed by dietary
      counseling in RARs without NP. Reduced sodium excretion and decreased NUV were
      significantly correlated (Spearman rho = 0.45, P = .005). CONCLUSION: Excess
      intake of sodium is considered a cause of NP in RARs. Dietary counseling on
      sodium restriction is effective in reducing NUV in RARs. Prospective studies are
      needed to evaluate the general population with NP.

PMID- 28456543
TI  - Subchronic toxicity of low dose propoxur, permethrin, and their combination on
      the redox status of rat liver.
AB  - Carbamates and pyrethroids are widely used pesticides. However, their joint
      toxicity at low doses with long-term exposure remains unknown. Therefore, we
      investigated the subchronic joint hepatotoxicity of the two representative
      pesticides within these two classes, i.e., propoxur (PR) and permethrin (PE) in
      rats. The male Wistar rats were orally treated with three different doses of PR,
      PE and their mixtures for 90 consecutive days. Liver weight, serum clinical
      chemistry parameters and histopathological changes were measured to access the
      hepatotoxicity. In addition, oxidative stress markers in liver were measured
      using biochemical assays. The results showed that PR reduced liver weight and
      lead to prominent liver histological changes. Moreover, PR dose-dependently
      induced lipid peroxidation and reduced superoxide dismutase activity. In
      contrast, PE induced a relatively mild hepatotoxicity. Intriguingly, the mixture
      of PR and PE did not reduce liver weight or increase serum aspartate transaminase
      activity. In addition, the mixture did not reduce the antioxidant enzyme activity
      as PR did. Thus, these results showed that PR induced prominent hepatotoxicity
      with subchronic exposure, and there is a potential antagonistic interaction
      between PR and PE on the oxidative damage in liver of rats.

PMID- 28456544
TI  - Gastroprotective effect of gamma-aminobutyric acid against ethanol-induced
      gastric mucosal injury.
AB  - The present study aimed to investigate the gastroprotective effect of gamma
      aminobutyric acid (GABA) on ethanol-induced gastric mucosal injury and gastric
      epithelial cells injury. Rats were divided into the control group, vehicle group
      and GABA-treated groups (10, 20 and 40 mg/kg/day). After GABA ingestion for 14
      days, rats except the control group were given 1 mL pure ethanol by oral gavage
      in order to induce acute gastric mucosal lesion. The human gastric epithelial
      cell line GES-1 was incubated with GABA (100, 200 and 400 MUM) for 24 h, followed
      by treatment with 8% ethanol for 3 h to induce cell injury. The results showed
      that GABA pretreatment significantly reduced gastric ulcer index in a dose
      dependent manner. GABA pretreatment could not only remarkably restrain oxidative
      stress by increasing activities of superoxide dismutase and catalase as well as
      decreasing content of malondialdehyde both in gastric tissue and cells, but also
      significantly reduced pro-inflammatory factors (interleukin-6 and tumor necrosis
      factor alpha) levels in gastric tissue. In addition, significant augments of
      prostaglandin E2 and nitric oxide levels were observed in the gastric tissues of
      40 mg/kg/d GABA treated group. In conclusion, the results in this study suggested
      that GABA could alleviate ethanol-induced gastric mucosal injury and gastric
      epithelial cells injury through the improvement of anti-inflammatory and anti
      oxidant status, as well as the increase of PGE2 and NO levels.

PMID- 28456545
TI  - Galectin-3 in acute coronary syndrome.
AB  - Acute coronary syndrome (ACS) is a very common cause of hospitalizations
      worldwide each year. In the past decades biomarkers have become an indispensable
      tool for diagnosis, risk stratification and prognosis of cardiovascular disease,
      including ACS. Despite Troponin is considered the gold standard in diagnosis of
      ACS, several molecules have been investigated to identify predictive biomarkers
      of prognosis. Among these, Gal-3 has emerged as a promising prognostic marker. It
      has a pivotal role in inflammation and fibrosis. Both experimental and clinical
      studies have shown Gal-3 is an independent predictor of all-cause mortality,
      cardiovascular death and occurrence of HF following ACS. This article reviews the
      literature data regarding the role of Galectin-3 in ACS setting.

PMID- 28456546
TI  - Causes of Diplopia in Patients With Epiretinal Membranes.
AB  - PURPOSE: To describe the causes of diplopia in patients with an epiretinal
      membrane (ERM) and presenting diplopia. DESIGN: Retrospective observational case
      series. METHODS: We reviewed patients diagnosed with an ERM, who had been seen by
      both retinal and strabismus specialists in a tertiary medical center. Data
      recorded: orthoptic evaluation, retinal misregistration (optotype-frame test, and
      synoptophore central peripheral superimposition slides at 5 and 10 degrees), and
      cause of any diplopia (retinal misregistration vs strabismus vs
      optical/refractive error). We defined central-peripheral rivalry-type diplopia as
      presenting symptomatic diplopia with evidence of retinal misregistration, and
      where other causes did not fully explain diplopia. The frequency of each cause of
      diplopia in patients with ERM was determined. RESULTS: Of 50 patients with ERM,
      25 had symptomatic diplopia and 25 had no diplopia. Eleven of 25 diplopic
      patients (44%) had retinal misregistration as the sole cause (central-peripheral
      rivalry-type diplopia), 7 (28%) strabismus (1 of 7 initally appeared to have
      central-peripheral rivalry-type diplopia), 1 (4%) optical/refractive error
      (monocular diplopia), 2 (8%) mixed retinal misregistration (central-peripheral
      rivalry-type diplopia) and strabismus, and for 4 (16%) diplopia cause was
      indeterminate. Unexpectedly, 15 of 25 patients without diplopia (60%) had
      evidence of retinal misregistration. CONCLUSIONS: Patients with ERM and
      presenting diplopia may have 1 of several causes of diplopia, most commonly
      retinal misregistration (central-peripheral rivalry-type diplopia). Nevertheless,
      diplopic patients with retinal misregistration may also have treatable strabismus
      or optical/refractive error as the primary barrier to single vision and therefore
      many potential barriers to single vision should be considered.

PMID- 28456547
TI  - Visual Outcomes Following Bilateral lmplantation of Two Diffractive Trifocal
      Intraocular Lenses in 10 084 Eyes.
AB  - PURPOSE: To investigate refractive and visual acuity outcomes, patient
      satisfaction, and spectacle independence at 3 months of 2 diffractive (non-toric)
      trifocal intraocular lenses (IOLs) in a large series of patients. DESIGN:
      Multicenter, retrospective, nonrandomized clinical study. METHODS: Patients
      underwent lens phacoemulsification and were implanted bilaterally with a
      diffractive trifocal IOL: FineVision Micro F (PhysIOL SA, Liege, Belgium) or AT
      Lisa tri 839MP (Carl Zeiss AG, Jena, Germany). Surgeries were performed between
      2011 and 2015 with at least 3 months of follow-up. Visual and refractive
      performance, patient satisfaction, and spectacle independence were evaluated.
      RESULTS: A total of 10 084 trifocal IOLs were bilaterally implanted (5802
      FineVision in 2901 patients and 4282 AT Lisa in 2141 patients). Three-month mean
      (+/- standard deviation) acuity: AT Lisa, binocular uncorrected distance visual
      acuity (UDVA), -0.01 logMAR +/- 0.06; monocular distance corrected visual acuity
      (CDVA), 0.02 logMAR +/- 0.06; binocular uncorrected near visual acuity (UNVA) at
      40 cm, 0.05 logMAR +/- 0.08; binocular uncorrected intermediate visual acuity
      (UIVA) at 80 cm, -0.05 logMAR +/- 0.14; postoperative spherical equivalent, 0.26
      D +/- 0.47; cylinder -0.34 D +/- 0.38; FineVision Micro F, binocular UDVA, 0.01
      logMAR +/- 0.05; monocular CDVA, 0.03 logMAR +/- 0.06; binocular UNVA, 0.05
      logMAR +/- 0.08; binocular UIVA, -0.05 logMAR +/- 0.12; spherical equivalent,
      0.34 D +/- 0.50; cylinder -0.39 D +/- 0.40. The IOLs were equivalent in achieving
      spectacle independence; 98% were "satisfied" to "very satisfied" with their IOL
      performance. CONCLUSIONS: In this retrospective study with over 5000 patients,
      implantation of both trifocal IOL models provided good functional distance,
      intermediate, and near visual acuity, resulting in high levels of both spectacle
      independence and patient satisfaction.

PMID- 28456551
TI  - 41st Anniversary Annual Meeting of the Developmental Neurotoxicology Society Held
      in Conjunction with the 57th Annual Meeting of the Teratology Society Grand Hyatt
      Hotel, Denver CO June 24-28, 2017.

PMID- 28456550
TI  - New optimism to the use of clinical scoring systems for the diagnosis of child
      tuberculosis - even among HIV co-infected.

PMID- 28456549
TI  - The interplay between the cellular hypoxic response and Notch signaling.
AB  - The ability to sense and adapt to low oxygen levels (hypoxia) is central for most
      organisms and cell types. At the center of this process is a molecular mechanism,
      the cellular hypoxic response, in which the hypoxia inducible factors (HIFs) are
      stabilized by hypoxia, allowing the HIF proteins to act as master transcriptional
      regulators to adjust the cell to a low oxygen environment. In recent years, it
      has become increasingly appreciated that the cellular hypoxic response does not
      always operate in splendid isolation, but intersects with signaling mechanisms
      such as Notch signaling, a key regulatory signaling mechanism operating in most
      cell types controlling stem cell maintenance and differentiation. In this review,
      which is dedicated to the memory of Lorenz Poellinger,1 we discuss how the
      intersection between Notch and the cellular hypoxic response was discovered and
      our current understanding of the molecular basis for the cross-talk. We also
      provide examples of where Notch and hypoxia intersect in various physiological
      and disease contexts.

PMID- 28456548
TI  - Changes in albumin-to-creatinine ratio at 12-month follow-up in patients
      undergoing renal denervation.
AB  - INTRODUCTION: Sympathetic renal denervation (RDN) was developed as a treatment
      for the management of patients with resistant hypertension. This procedure may
      have a positive impact on hypertension-related target organ damage, particularly
      renal disease, but the evidence is still limited. OBJECTIVE: To assess the impact
      of RDN on the albumin-to-creatinine ratio (ACR) at 12-month follow-up. METHODS
      AND RESULTS: From a single-center prospective registry including 65 patients with
      resistant hypertension undergoing renal denervation, 31 patients with complete
      baseline and 12-month follow-up blood pressure (BP) measurements (both office and
      24-h ambulatory blood pressure monitoring [ABPM]) and ACR were included in the
      present study. Mean age was 65+/-7 years, 52% were female, most (90%) had been
      diagnosed with hypertension for more than 10 years, 71% had type 2 diabetes and
      33% had vascular disease in at least one territory. Mean estimated glomerular
      filtration rate was 73.6+/-25.1 ml/min/1.73 m2 and 15 patients (48%) had an ACR
      >30 mg/g. After 12 months, 22 patients were considered BP responders (73%). ACR
      decreased significantly from a median of 25.8 mg/g (interquartile range [IQR] 9.0
      574.0 mg/g) to 14.8 mg/g (IQR 4.5-61.0 mg/g, p=0.007). When the results were
      split according to systolic BP responder status on ABPM, we found a significant
      reduction in responders (from 25.6 mg/g [IQR 8.7-382.8 mg/g] to 15.9 mg/g [IQR
      4.4-55.0 mg/g], p=0.009), and a numerical decrease in the non-responder subgroup
      (from 165.0 mg/g [IQR 8.8-1423.5 mg/g] to 13.6 mg/dl [IQR 5.7-1417.0 mg/g],
      p=0.345). CONCLUSIONS: Besides significant reductions in blood pressure (both
      office and 24-h ABPM), renal denervation was associated with a significant
      reduction in ACR, a recognized marker of target organ damage.

PMID- 28456552
TI  - Subtyping of Canadian isolates of Salmonella Enteritidis using Multiple Locus
      Variable Number Tandem Repeat Analysis (MLVA) alone and in combination with
      Pulsed-Field Gel Electrophoresis (PFGE) and phage typing.
AB  - Salmonella enterica subspecies enterica serovar Enteritidis (SE) is one of the
      most common causes of human salmonellosis and in Canada currently accounts for
      over 40% of human cases. Reliable subtyping of isolates is required for outbreak
      detection and source attribution. However, Pulsed-Field Gel Electrophoresis
      (PFGE), the current standard subtyping method for Salmonella spp., is compromised
      by the high genetic homogeneity of SE. Multiple Locus Variable Number Tandem
      Repeat Analysis (MLVA) was introduced to supplement PFGE, although there is a
      lack of data on the ability of MLVA to subtype Canadian isolates of SE. Three
      subtyping methods, PFGE, MLVA and phage typing were compared for their
      discriminatory power when applied to three panels of Canadian SE isolates: Panel
      1: 70 isolates representing the diversity of phage types (PTs) and PFGE subtypes
      within these PTs; Panel 2: 214 apparently unrelated SE isolates of the most
      common PTs; and Panel 3: 27 isolates from 10 groups of epidemiologically related
      strains. For Panel 2 isolates, four MLVA subtypes were shared among 74% of
      unrelated isolates and in Panel 3 isolates, one MLVA subtype accounted for 62% of
      the isolates. For all panels, combining results from PFGE, MLVA and PT gave the
      best discrimination, except in Panel 1, where the combination of PT and PFGE was
      equally as high, due to the selection criteria for this panel. However, none of
      these methods is sufficiently discriminatory alone for reliable outbreak
      detection or source attribution, and must be applied together to achieve
      sufficient discrimination for practical purposes. Even then, some large clusters
      were not differentiated adequately. More discriminatory methods are required for
      reliable subtyping of this genetically highly homogeneous serovar. This need will
      likely be met by whole genome sequence analysis given the recent promising
      reports and as more laboratories implement this tool for outbreak response and
      surveillance.

PMID- 28456553
TI  - An unusual spinaceamine-bearing pregnane from a soft coral Scleronephthya sp.
      inhibits the migration of tumor cells.
AB  - An unprecedented spinaceamine-bearing pregnane namely scleronine (1) was isolated
      from a Chinese soft coral Scleronephthya sp. Its structure was determined on the
      basis of 1D and 2D NMR spectroscopic analyses in association with the HRESIMS
      data, while the absolute configurations were deduced by the single-crystal X-ray
      diffraction analysis. In addition, a dehydrogenated analogue (3) was synthesized
      through six steps with pregna-1,20-dien-3-one (2) as a precursor. The
      significantly inhibitory effects of 1 and 3 against the migration of tumor cells
      A549 and B16 accompanying the down-regulation of key genes (TGFbeta, TNFalpha, IL
      1beta, and IL-6) were observed. These findings suggested that both 1 and 3 are
      potential for therapeutic usage aiming at cancer metastasis inhibition.

PMID- 28456554
TI  - Triterpenoids and iridoids from Patrinia scabiosaefolia.
AB  - Three new triterpenoids, patrinolides B-D (1-3), and two new iridoids,
      patriscabioins K-L (9-10), together with five known compounds (4-8) were isolated
      from the extract of the whole plants of Patrinia scabiosaefolia. Compounds 1, 9,
      and 10 contained the unique substituents in Valerianaceae family, such as
      isovalery and 3-methylcrotonyl. Compound 2 was a 24-nor-ursane triterpenoid.
      Their structures were established on the basis of extensive spectroscopic
      analysis (UV, IR, MS, 1D and 2D NMR). The inhibitory activities against nitric
      oxide synthase (NOS) of all triterpenoids were tested. The results showed that
      compound 4 had moderate inhibitory activity with IC50 of 10.1MUM. Furthermore, it
      also showed strongest inhibitory activities on AChE with IC50 values of 10.0MUM.

PMID- 28456555
TI  - Experimental and theoretical calculation studies on the structure elucidation and
      absolute configuration of calyxins from Alpinia katsumadai.
AB  - Six novel calyxins, named calyxin T-W, ent-calyxin T and ent-calyxin U were
      isolated from the seeds of Alpinia katsumadai Hayata. Their relative
      configurations were elucidated by means of detailed UV, IR, NMR and MS
      spectroscopic data. Their absolute configurations were assigned by collaborative
      studies on single crystal X-ray diffraction analysis, Mosher's method, electronic
      circular dichroism (ECD), optical rotation and theoretical calculations. These
      compounds are Friedel-Cranft alkylation adducts composed of coexisted
      diarylheptanoids and flavanone from the seeds of Alpinia katsumadai. The
      antiproliferative activity of the six compounds against NCI-H460, HeLa, SMMC-7721
      and HCT-116 cell lines was also reported, and most of them showed moderate to
      strong activities.

PMID- 28456556
TI  - Evaluation of the Cariogram for root caries prediction.
AB  - OBJECTIVES: The aim of this study was to evaluate complete and reduced Cariogram
      models in predicting root caries risk in independently living older adults by
      comparing the caries risk assessment of the programme to observed root caries
      increment over a two-year period. METHODS: A prospective study recording root
      caries incidence was conducted on 334 dentate older adults. Data were collected
      on participant's medical history, fluoride exposure, and diet. Saliva samples
      were collected to measure salivary flow rate, buffer capacity and bacterial
      counts. Clinical examination was completed to record decayed, missing and filled
      teeth (DMFT) and also exposed, filled and decayed root surfaces (RDFS). This was
      repeated after 12 and 24 months. Scores were entered into the Cariogram and
      baseline risk category was recorded. Reduced Cariogram models were generated by
      omitting individual salivary variables and all salivary variables. The
      performance of the complete and reduced Cariogram models in predicting root
      caries incidence were evaluated by receiver operating characteristic (ROC)
      analysis. RESULTS: 280 participants were examined at two year follow up. 55.6% of
      those in the highest risk group developed new caries compared to 3.8% in the
      lowest risk group. The mean root caries increment in the highest risk group was
      2.00 (SD 3.20) compared to 0.04 (SD 0.20) in the lowest risk group. The area
      under the ROC curve for the complete Cariogram model was 0.77 (95% CI 0.70-0.83)
      indicating a fair performance in predicting root caries. Omitting individual or
      all salivary variables did not significantly alter the predictive ability of the
      Cariogram. CONCLUSION: Within the limitations of this study, the Cariogram was
      clinically useful in identifying individuals with a high risk of developing root
      caries. CLINICAL SIGNIFICANCE: Identification of a caries risk assessment tool
      which could reliably select high-risk individuals for root caries prevention
      strategies would maximise the cost effectiveness of professionally delivered
      prevention measures.

PMID- 28456557
TI  - No post-no core approach to restore severely damaged posterior teeth: An up to 10
      year retrospective study of documented endocrown cases.
AB  - OBJECTIVES: The objectives of the present study were to (1) retrospectively
      evaluate documented cases of ceramic and composite endocrowns performed using
      immediate dentin sealing (IDS); (2) correlate failures with clinical parameters
      such as tooth preparation characteristics and occlusal parameters. METHODS: 99
      documented cases of endocrowns were evaluated after a mean observation period of
      44.7+/-34.6months. A classification of restorations was established in function
      of the level of damage of residual tooth tissues after preparation, from 1 to 3.
      Evaluation was performed according to FDI criteria and endodontic outcomes were
      analyzed. Occlusal risk factors were examined and fractographic analysis was
      performed in case of fracture. RESULTS: 48.4% of patients were shown to present
      occlusal risk factors. 75.8% of restorations were Class 3 endocrowns. 56.6% were
      performed on molars, 41.4% on premolars and 2.0% on canines. 84.8% were performed
      in lithium-disilicate glass-ceramic and 12.1% in Polymer-Infiltrated Ceramic
      Network (PICN) material. The survival and success rates of endocrowns were 99.0%
      and 89.9% respectively, while the 10-year Kaplan-Meier estimated survival and
      success rates were 98.8% and 54.9% respectively. Ten failures were detected:
      periodontal disease (n=3), endocrown debonding (n=2), minor chipping (n=2),
      caries recurrence (n=2) and major fractures (n=1). Due to the reduced amount of
      failures, no statistical correlation could be established with clinical
      parameters. CONCLUSIONS: Endocrowns were shown to constitute a reliable approach
      to restore severely damaged molars and premolars, even in the presence of
      extensive coronal tissue loss or occlusal risk factors, such as bruxism or
      unfavorable occlusal relationships. CLINICAL SIGNIFICANCE: Practitioners should
      consider the endocrown instead of the post and core approach to restore severely
      damaged non-vital posterior teeth. This minimally invasive solution reduces the
      risk of catastrophic failures and is easily performed. The use of IDS procedure
      and lithium-disilicate glass-ceramic as prosthesis material gave very good
      results.

PMID- 28456558
TI  - Removal of an Infected Total Hip Arthroplasty: Risk Factors for Repeat
      Debridement, Long-term Spacer Retention, and Mortality.
AB  - BACKGROUND: Two-stage exchange arthroplasty remains the preferred approach to
      treatment of chronic periprosthetic joint infection (PJI) following total hip
      arthroplasty (THA). The objective of the present study is to investigate the fate
      of antibiotic spacers placed for periprosthetic joint infection after THA and
      evaluate risk factors for outcomes other than reimplantation. METHODS: A national
      database was queried for Medicare patients who underwent removal of an infected
      hip prosthesis and placement of an antibiotic spacer. Patients with a study end
      point within 1 year postoperatively were included: (1) in-hospital mortality, (2)
      repeat debridement without reimplantation within 1 year, (3) resection
      arthroplasty, and (4) reimplantation of a hip arthroplasty. Independent patient
      related risk factors for these end points were evaluated with a multivariate
      logistic regression analysis. RESULTS: A total of 7146 patients met all inclusion
      and exclusion criteria. Within 1 year postoperatively, 464 patients (6.5%) died
      in a hospital setting, 775 patients (10.8%) had a repeat debridement procedure,
      404 patients (5.7%) had a resection arthroplasty, 1202 patients (16.8%) retained
      their spacers, and the remaining 4301 patients (60.2%) were reimplanted at an
      average of 124.4 +/- 39.3 days. Numerous independent patient-related risk factors
      for these were identified. CONCLUSION: At 1 year only 60% of patients undergo
      reimplantation. One-sixth of patients retain their spacer and approximately 10%
      require repeat debridement. Death occurred in at least 6% of the population.
      Several independent patient-related risk factors exist for repeat debridement, no
      reimplantation or death within 1 year following index THA removal.

PMID- 28456559
TI  - Midterm Outcomes of Revision Total Hip Arthroplasty With the Use of a Multihole
      Highly-Porous Titanium Shell.
AB  - BACKGROUND: We are reporting on the minimum 5-year outcomes of patients who
      underwent revision total hip arthroplasty (THA) using a specific highly-porous
      titanium shell. We assessed (1) aseptic and all-cause survivorship; (2)
      functional outcomes; (3) complications; and (4) radiographic outcomes. METHODS:
      Two hospital databases were evaluated for patients who underwent revision THA due
      to component instability or aseptic loosening using a cementless highly-porous
      titanium shell between September 2006 and December 2011. This yielded 35 patients
      who had a mean age of 61 years (range 14-88 years). Patients had a mean follow-up
      of 6 years (minimum 5 years). All-cause and aseptic survivorship of the shell was
      calculated. Functional outcomes were assessed using the Harris Hip Score. We
      determined the incidence of postoperative complications and performed
      radiographic evaluation of pelvic radiographs from regular office visits. RESULT:
      The aseptic survivorship of the acetabular component was 97% (95% confidence
      interval; 8.1-9.5). The all-cause survivorship of the acetabular component was
      91% (95% confidence interval; 7.3-8.1). One patient had an aseptic failure and 2
      patients had septic failures. The mean postoperative Harris Hip Score was 76
      points (range, 61-91 points). Excluding the aseptic and septic failures, there
      was no osteolysis or progressive radiolucencies present on radiographic
      evaluation at final follow-up. CONCLUSION: At a minimum of 5-year follow-up, the
      highly-porous titanium acetabular revision shell has excellent survivorship and
      functional outcomes. Although long-term follow-up is needed to further monitor
      these implants, the results are promising and demonstrate that this prosthesis
      may be an excellent option for patients undergoing revision THA.

PMID- 28456560
TI  - Social Media and Total Joint Arthroplasty: An Analysis of Patient Utilization on
      Instagram.
AB  - BACKGROUND: The purpose of this study was to analyze the nature of shared content
      of total joint arthroplasty patients on Instagram. Specifically, we evaluated
      social media posts for: (1) perspective and timing; (2) tone; (3) focus
      (activities of daily living [ADLs], rehabilitation, return-to-work); and (4) the
      comparison between hip and knee arthroplasties. METHODS: A search of the public
      Instagram domain was performed over a 6-month period. Total hip and knee
      arthroplasties (THA and TKA) were selected for the analysis using the following
      terms: "#totalhipreplacement," "#totalkneereplacement," and associated terms.
      1287 individual public posts of human subjects were shared during the period. A
      categorical scoring system was utilized for media format (photo or video), time
      (preoperative, perioperative, or postoperative) period, tone (positive or
      negative), return-to-work, ADLs, rehabilitation, surgical site, radiograph image,
      satisfaction, and dissatisfaction. RESULTS: Ninety-one percent of the posts were
      shared during the postoperative period. Ninety-three percent of posts had a
      positive tone. Thirty-four percent of posts focused on both ADLs and 33.8% on
      rehabilitation. TKA patients shared more about their surgical site (14.5% vs
      3.3%, P < .001) and rehabilitation (58.9% vs 8.8%, P < .001) than THA patients,
      whereas THA patients shared more about ADLs than TKA patients (60.5% vs 7.6%, P <
      .001). CONCLUSION: When sharing their experience on Instagram, arthroplasty
      patients did so with a positive tone, starting a week after surgery. TKA posts
      focused more on rehabilitation and wound healing than THA patients, whereas THA
      patients shared more posts on ADLs. The analysis of social media posts provides
      insight into what matters to patients after total joint arthroplasty.

PMID- 28456561
TI  - Current Epidemiology of Revision Total Knee Arthroplasty in the United States.
AB  - BACKGROUND: Revision surgery for failed total knee arthroplasty (TKA) continues
      to pose a substantial burden for the United States healthcare system. The
      predominant etiology of TKA failure has changed over time and may vary between
      studies. This report aims to update the current literature on this topic by using
      a large national database. Specifically, we analyzed: (1) etiologies for revision
      TKA; (2) frequencies of revision TKA procedures; (3) various demographics
      including payer type and region; and (4) the length of stay (LOS) and total
      charges based on type of revision TKA procedure. METHODS: The Healthcare Cost and
      Utilization Project (HCUP) National Inpatient Sample (NIS) database was used to
      identify all revision TKA procedures performed between 2009 and 2013. Clinical,
      economic, and demographic data were collected and analyzed for 337,597
      procedures. Patients were stratified according to etiology of failure, age, sex,
      race, US census region, and primary payor class. The mean LOS and total charges
      were also calculated. RESULTS: Infection was the most common etiology for
      revision TKA (20.4%), closely followed by mechanical loosening (20.3%). The most
      common revision TKA procedure performed was all component revision (31.3%).
      Medicare was the primary payor for the greatest proportion of revisions (57.7%).
      The South census region performed the most revision TKAs (33.2%). The overall
      mean LOS was 4.5 days, with arthrotomy for removal of prosthesis without
      replacement procedures accounting for the longest stays (7.8 days). The mean
      total charge for revision TKAs was $75,028.07. CONCLUSION: Without appropriate
      measures in place, the burden of revision TKAs may become overwhelming and pose a
      strain on providers and institutions. Continued insight into the etiology and
      epidemiology of revision TKAs may be the principle step towards improving
      outcomes and mitigating the need for future revisions.

PMID- 28456562
TI  - Withholding Preoperative Antibiotic Prophylaxis in Knee Prosthesis Revision: A
      Retrospective Analysis on Culture Results and Risk of Infection.
AB  - BACKGROUND: A significant amount of patients undergoing revision surgery of a
      prosthetic joint turn out to have an infection. Withholding preoperative
      antibiotic prophylaxis in these patients to optimize culture yield during
      revision surgery remains a matter of debate. The aim of our study was to
      determine (1) the rate of positive intraoperative cultures with or without
      preoperative antibiotic prophylaxis and (2) the incidence of a prosthetic joint
      infection (PJI) during the follow-up in the 2 groups. METHODS: Medical files of
      patients in whom preoperative antibiotic prophylaxis was withheld until culture
      samples were taken (2007-2010, n = 284) and in whom antibiotic prophylaxis was
      given during the induction of anesthesia (2010-2013, n = 141) were
      retrospectively reviewed. RESULTS: The percentage of >=1 positive cultures was
      the same in the group without (26%) and with preoperative prophylaxis (27%; P
      value, .7). PJI was diagnosed during revision surgery according to the
      Musculoskeletal Infection Society criteria in 6.7% patients not receiving
      preoperative prophylaxis and in 7.0% receiving it (P value, .79). We found no
      important differences in the type of microorganisms that were isolated in both
      groups. During a 3-month follow-up, an early PJI developed in patients undergoing
      total revision surgery in 6.4% of the nonpreoperative prophylaxis group vs 1.6%
      in the preoperative prophylaxis group (P value, .1). CONCLUSION: Preoperative
      antibiotic prophylaxis does not reduce culture yield in patients undergoing knee
      revision surgery. Our data show a trend toward a higher PJI rate in the
      postoperative period of total revision surgery when preoperative prophylaxis is
      withheld.

PMID- 28456563
TI  - Total Knee Arthroplasty for Osteoarthritis in Patients Less Than Fifty-Five Years
      of Age: A Systematic Review.
AB  - BACKGROUND: The proportion of younger patients undergoing total knee arthroplasty
      (TKA) is increasing and predictions state that the <55 age group will be the
      fastest growing group by 2030. We aim to collate data across studies to assess
      functional outcomes following TKA in patients <55 years of age using a systematic
      review. METHODS: The search identified 980 studies for title and abstract review.
      Forty-three full texts were then assessed. Thirteen studies underwent quality
      assessment and data extraction. Preferred Reporting Items for Systematic Reviews
      and Meta-analyses guidelines were followed throughout. Outcomes extracted
      included pre-operative and post-operative functional scores, range of motion, and
      patient satisfaction. Clinical complications and survival were also recorded.
      RESULTS: Across 13 studies we were able to demonstrate 54-point improvement in
      clinical Knee Society Score and a 46-point improvement on functional Knee Society
      Score. A 2.9 degrees  improvement in range of motion was found at final follow
      up. Satisfaction rate was 85.5%. Cumulative percentage all-cause revision rate
      was 5.4% across 1283 TKAs at a mean 10.8 years of follow-up. Ten-year survival,
      for aseptic loosening alone, was 98.2%. CONCLUSION: TKA is an excellent treatment
      option for the young osteoarthritic knee with a >50% improvement in functional
      knee scores. Satisfaction is high and the revision rate remains 0.5% per year.

PMID- 28456564
TI  - Respiratory and hemodynamic contributions to emotion-related pre-syncopal
      vasovagal symptoms.
AB  - Vasovagal reactions are conventionally understood as resulting from systemic
      changes in cardiovascular activity; however, there exists a complementary
      perspective focused on specific changes in cerebral vasoconstriction associated
      with hyperventilation-induced hypocapnia. The present study investigated the role
      of cardiovascular and respiratory activity in self-reported pre-syncopal
      vasovagal reactions to a surgery video in a sample of 49 healthy women.
      Participants who indicated more previous real-life episodes of dizziness reported
      experiencing significantly more symptoms in the laboratory consistent with a
      vasovagal response. They also showed lower total peripheral resistance and higher
      pre-ejection period in general, suggesting lower sympathetic nervous system
      activity. Significant decreases in end-tidal carbon dioxide (PETCO2) occurred
      during the surgery video among susceptible participants, without significant
      increases in respiration rate. Further, participants who experienced reductions
      from the neutral video in PETCO2, systolic blood pressure, or both, reported
      vasovagal symptoms during the surgery video. The results suggest that patterns of
      respiration associated with decreases in PETCO2 may contribute to vasovagal
      symptoms reported in non-clinical groups as well as those with blood-injection
      injury phobia and are associated with susceptibility to dizziness.

PMID- 28456565
TI  - Red blood cell membrane water permeability increases with length of ex vivo
      storage.
AB  - Water transport across the red blood cell (RBC) membrane is an essential cell
      function that needs to be preserved during ex vivo storage. Progressive
      biochemical depletion during storage can result in significant conformational and
      compositional changes to the membrane. Characterizing the changes to RBC water
      permeability can help in evaluating the quality of stored blood products and aid
      in the development of improved methods for the cryopreservation of red blood
      cells. This study aimed to characterize the water permeability (Lp), osmotically
      inactive fraction (b), and Arrhenius activation energy (Ea) at defined storage
      time-points throughout storage and to correlate the observed results with other
      in vitro RBC quality parameters. RBCs were collected from age- and sex-matched
      blood donors. A stopped flow spectrophotometer was used to determine Lp and b by
      monitoring changes in hemoglobin autofluorescence when RBCs were exposed to
      anisotonic solutions. Experimental values of Lp were characterized at three
      different temperatures (4, 20 and 37  degrees C) to determine the Ea. Results
      showed that Lp, b, and Ea of stored RBCs significantly increase by day 21 of
      storage. Degradation of the RBC membrane with length of storage was seen as an
      increase in hemolysis and supernatant potassium, and a decrease in deformability,
      mean corpuscular hemoglobin concentration and supernatant sodium. RBC osmotic
      characteristics were shown to change with storage and correlate with changes in
      RBC membrane quality metrics. Monitoring water parameters is a predictor of
      membrane damage and loss of membrane integrity in ex vivo stored RBCs.

PMID- 28456566
TI  - Assessment of acute and chronic toxicity of doxorubicin in human induced
      pluripotent stem cell-derived cardiomyocytes.
AB  - The present study assesses acute and chronic toxicity of doxorubicin in human
      induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), with the aim to
      obtain in vitro biomarkers that can be used as readouts to predict in vivo
      cardiotoxicity. Possible acute toxicity was investigated by assessing effects on
      the beating rate and the field potential duration (FPD) of doxorubicin-exposed
      cardiomyocytes by measuring electrical activity using multi-electrode array (MEA)
      analyses. No effects on the beating rate and FPD were found at concentrations up
      to 6MUM, whereas at 12MUM no electrical activity was recorded, indicating that
      the cardiomyocytes stopped beating. Acute and chronic effects of doxorubicin on
      mitochondria, which have been reported to be affected in doxorubicin-induced
      cardiotoxicity, were assessed using high content imaging techniques. To this end
      hiPSC-CMs were exposed to 150 or 300nM doxorubicin using both single dosing (3h
      and 2days) and repetitive dosing (3 times, of 2days each), including washout
      studies to assess delayed effects (assessment at day 14) and effects on cell
      number, mitochondrial density, mitochondrial membrane potential, mitochondrial
      superoxide levels and mitochondrial calcium levels were assessed. No effects of
      doxorubicin were found on mitochondrial density and mitochondrial superoxide
      levels, whereas doxorubicin reduced cell survival and slightly altered
      mitochondrial membrane potential and mitochondrial calcium levels, which was most
      profound in the washout studies. Altogether, the results of the present study
      show that concentrations of doxorubicin in the micromolar range were required to
      affect electrical activity of hiPSC-CMs, whereas nanomolar concentrations already
      affected cell viability and caused mitochondrial disturbances. Integration of
      these data with other in vitro data may enable the selection of a series of in
      vitro biomarkers that can be used as readouts to screen chemicals for possible
      cardiotoxicity.

PMID- 28456567
TI  - Synthesis and cytotoxic activity of new artemisinin hybrid molecules against
      human leukemia cells.
AB  - A series of new artemisinin-derived hybrids which incorporate cholic acid
      moieties have been synthesized and evaluated for their antileukemic activity
      against sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cells. The new
      hybrids 20-28 showed IC50 values in the range of 0.019uM-0.192uM against CCRF-CEM
      cells and between 0.345uM and 7.159uM against CEM/ADR5000 cells. Amide hybrid 25
      proved the most active compound against both CCRF-CEM and CEM/ADR5000 cells with
      IC50 value of 0.019+/-0.001uM and 0.345+/-0.031uM, respectively. A relatively low
      cross resistance to hybrids 20-28 in the range of 5.7-fold to 46.1-fold was
      measured. CEM/ADR5000 cells showed higher resistance than CCRF-CEM to all the
      tested compounds. Interestingly, the lowest cross resistance to 23 was observed
      (5.7-fold), whereas hybrid 25 showed 18.2-fold cross-resistant to CEM/ADR5000
      cells. Hybrid 25 which proved even more potent than clinically used doxorubicin
      against CEM/ADR5000 cells may serve as a promising antileukemic agent against
      both sensitive and multidrug-resistant cells.

PMID- 28456568
TI  - Acylamino acid chiral fungicides on toxiciepigenetics in lambda DNA methylation.
AB  - Acylamino acid chiral fungicides (AACFs) are low-toxicity pesticides and
      considered as non-carcinogenic chemicals to laboratory animals. Though AACFs have
      potential toxicological effects on mammals by non-genotoxic mechanisms, the
      toxicoepigenomics of AACFs has not been documented. In this article, we explored
      toxiciepigenetics of metalaxyl, benalaxyl and furalaxyl through epigenetics
      research on lambda DNA under different concentration exposure. The
      toxicoepigenomic difference of stereoisomers was examined also. Our results
      showed that AACFs would affect methyltransferase activity resulting in modulating
      DNA methylation levels and pattern. The LOAEL of R-metalaxyl and S-metalaxyl were
      30 mM and 0.3 mM, respectively. The LOAEL of (R, S)-benalaxyl and (R, S)
      furalaxyl were 0.3 Mm and 30 mM, respectively. A significant dose-response effect
      between (R, S)-benalaxyl and global methylation level was observed. Global
      methylation level was more susceptible to S-enantiomer compared to R-enantiomer,
      which indicated enantiomers of AACFs have the enantioselectivity in
      toxiciepigenetics. Moreover, the dependence of the methylation inhibition on the
      chiral center of metalaxyl may suggest a considerable specificity of the compound
      of AACFs for DNA methyltransferases. The inhibition effect between R-enantiomer
      and S-enantiomer of AACFs on DNA methylation levels generated in this study is
      important for low-toxicity pesticides toxicoepigenomics evaluation.

PMID- 28456569
TI  - Neural correlates of cognitive control in gambling disorder: a systematic review
      of fMRI studies.
AB  - Decreased cognitive control over the urge to be involved in gambling activities
      is a core feature of Gambling Disorder (GD). Cognitive control can be
      differentiated into several cognitive sub-processes pivotal in GD clinical
      phenomenology, such as response inhibition, conflict monitoring, decision-making,
      and cognitive flexibility. This article aims to systematically review fMRI
      studies, which investigated the neural mechanisms underlying diminished cognitive
      control in GD. We conducted a comprehensive literature search and collected
      neuropsychological and neuroimaging data investigating cognitive control in GD.
      We included a total of 14 studies comprising 499 individuals. Our results
      indicate that impaired activity in prefrontal cortex may account for decreased
      cognitive control in GD, contributing to the progressive loss of control over
      gambling urges. Among prefrontal regions, orbital and ventromedial areas seem to
      be a possible nexus for sensory integration, value-based decision-making and
      emotional processing, thus contributing to both motivational and affective
      aspects of cognitive control. Finally, we discussed possible therapeutic
      approaches aimed at the restoration of cognitive control in GD, including
      pharmacological and brain stimulation treatments.

PMID- 28456570
TI  - Beyond Correlations, Sensitivities, and Specificities: A Roadmap for
      Demonstrating Utility of Advanced Imaging in Oncology Treatment and Clinical
      Trial Design.
AB  - Despite the widespread belief that advanced imaging should be very helpful in
      guiding oncology treatment decision and improving efficiency and success rates in
      treatment clinical trials, its acceptance has been slow. Part of this is likely
      attributable to gaps in study design and statistical methodology for these
      imaging studies. Also, results supporting the performance of the imaging in these
      roles have largely been insufficient to justify their use within the design of a
      clinical trial or in treatment decision making. Statistically significant
      correlations between the imaging results and clinical outcomes are often
      incorrectly taken as evidence of adequate performance. Assessments of whether the
      imaging can outperform standard techniques or meaningfully supplement them are
      also frequently neglected. This paper provides guidance on study designs and
      statistical analyses for evaluating the performance of advanced imaging in the
      various roles in treatment decision guidance and clinical trial conduct. Relevant
      methodology from the imaging literature is reviewed; gaps in the literature are
      addressed using related concepts from the more extensive genomic and in vitro
      biomarker literature.

PMID- 28456571
TI  - Erythropoietin activates SIRT1 to protect human cardiomyocytes against
      doxorubicin-induced mitochondrial dysfunction and toxicity.
AB  - The hormone erythropoietin (EPO) has been demonstrated to protect against
      chemotherapy drug doxorubicin (DOX)-induced cardiotoxicity, but the underlying
      mechanism remains obscure. We hypothesized that silent mating type information
      regulation 2 homolog 1 (SIRT1), an NAD+-dependent protein deacetylase that
      activates peroxisome proliferator-activated receptor gamma coactivator 1-alpha
      (PGC-1alpha), plays a crucial role in regulating mitochondrial function and
      mediating the beneficial effect of EPO. Our study in human cardiomyocyte AC16
      cells showed that DOX-induced cytotoxicity and mitochondrial dysfunction, as
      manifested by decreased mitochondrial DNA (mtDNA) copy number, mitochondrial
      membrane potential, and increased mitochondrial superoxide accumulation, can be
      mitigated by EPO pretreatment. EPO was found to upregulate SIRT1 activity and
      protein expression to reverse DOX-induced acetylation of PGC-1alpha and
      suppression of a suite of PGC-1alpha-activated genes involved in mitochondrial
      function and biogenesis, such as nuclear respiratory factor-1 (NRF1),
      mitochondrial transcription factor A (TFAM), citrate synthase (CS), superoxide
      dismutase 2 (SOD2), cytochrome c oxidase IV (COXIV), and voltage-dependent anion
      channel (VDAC). Silencing of SIRT1 via small RNA interference sensitized AC16
      cells to DOX-induced cytotoxicity and reduction in mtDNA copy number. Although
      with SIRT1 silenced, EPO could reverse to some extent DOX-induced mitochondrial
      superoxide accumulation, loss of mitochondrial membrane potential and ATP
      depletion, it failed to normalize protein expression of PGC-1alpha and its
      downstream genes. Taken together, our results indicated that EPO may activate
      SIRT1 to enhance mitochondrial function and protect against DOX-induced
      cardiotoxicity.

PMID- 28456572
TI  - Treatment with sodium nitroprusside improves the endothelial function in aortic
      rings with endothelial dysfunction.
AB  - PURPOSE: Verify if sodium nitroprusside (SNP) is able to improve endothelial
      function and if this effect is independent of nitric oxide (NO) release of the
      compound. METHODS: Normotensive (2K) and hypertensive (2K-1C) wistar rats were
      used. Intact endothelium aortas were placed in a myograph and incubated with SNP:
      0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for
      acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular
      NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0.1nM or DETA/NO
      0.1MUM. The detection of intracellular superoxide radical (O2*-) was obtained by
      using DHE probe. RESULTS: Treatment of 2K-1C aortic rings with SNP (0.1; 1.0 and
      10nM) improved endothelium dependent relaxation induced by acetylcholine. This
      improvement induced by SNP was verified at the concentration of 0.1nM, which does
      not release NO, suggesting that this effect was not induced due to NO release by
      SNP compound. Besides, we show that the cell treatment with 0.1nM of SNP
      decreased the fluorescence intensity to DHE in cells stimulated with angiotensin
      II. These results indicate that SNP decreases the concentration of O2*- in HUVEC
      cells. CONCLUSIONS: The SNP at a concentration that does not release NO inside
      the cells is able to attenuate endothelial dysfunction. DRUGS AND CHEMICALS:
      Acetylcholine (Ach) (PubChem CID:6060); angiotensin II human (Ang II) (PubChem
      CID: 16211177); diethylenetriamine/nitric oxide (DETA-NO) (PubChem CID 4518);
      dihydroethidium (DHE) (PubChem CID: 128682); phenylephrine (Phe) (PubChem CID:
      5284443); sodium nitroprusside (SNP) (PubChem CID: 11963579); Thiazolyl Blue
      Tetrazolium Bromide (MTT) (PubChem CID: 64965); 4,5-diaminofluorescein diacetate
      (DAF-2DA); 4-hidroxy-Tempo (Tempol) (PubChem CID: 137994), were purchased from
      Sigma-Aldrich (St. Louis, MO, USA).

PMID- 28456573
TI  - Predictors for drug effects with brain disease: Shed new light from EEG
      parameters to brain connectomics.
AB  - Though researchers spent a lot of effort to develop treatments for
      neuropsychiatric disorders, the poor translation of drug efficacy data from
      animals to human hampered the success of these therapeutic approaches in human.
      Pharmaceutical industry is challenged by low clinical success rates for new drug
      registration. To maximize the success in drug development, biomarkers are
      required to act as surrogate end points and predictors of drug effects. The
      pathology of brain disease could be in part due to synaptic dysfunction.
      Electroencephalogram (EEG), generating from the result of the postsynaptic
      potential discharge between cells, could be a potential measure to bridge the
      gaps between animal and human data. Here we discuss recent progress on using
      relevant EEG characteristics and brain connectomics as biomarkers to monitor drug
      effects and measure cognitive changes on animal models and human in real-time. It
      is expected that the novel approach, i.e. EEG connectomics, will offer a deeper
      understanding on the drug efficacy at a microcirculatory level, which will be
      useful to support the development of new treatments for neuropsychiatric
      disorders.

PMID- 28456574
TI  - Suppression of Epstein-Barr virus DNA load in latently infected nasopharyngeal
      carcinoma cells by CRISPR/Cas9.
AB  - Epstein-Barr virus (EBV) infects more than 90% of the world's adult population.
      Once established, latent infection of nasopharyngeal epithelial cells with EBV is
      difficult to eradicate and might lead to the development of nasopharyngeal
      carcinoma (NPC) in a small subset of individuals. In this study we explored the
      anti-EBV potential of CRISPR/Cas9 targeting of EBV genome in infected NPC cells.
      We designed gRNAs to target different regions of the EBV genome and transfected
      them into C666-1 cells. The levels of EBV DNA in transfected cells were decreased
      by about 50%. The suppressive effect on EBV DNA load lasted for weeks but could
      not be further enhanced by re-transfection of gRNA. Suppression of EBV by
      CRISPR/Cas9 did not affect survival of C666-1 cells but sensitized them to
      chemotherapeutic killing by cisplatin and 5-fluorouracil. Our work provides the
      proof-of-principle for suppressing EBV DNA load with CRISPR/Cas9 and a potential
      new strategy to sensitize EBV-infected NPC cells to chemotherapy.

PMID- 28456575
TI  - Incorporation of the Kaposi's sarcoma-associated herpesvirus capsid vertex
      specific component (CVSC) into self-assembled capsids.
AB  - Self-assembly of herpesvirus capsids can be accomplished in heterologous
      expression systems provided all six capsid proteins are present. We have
      demonstrated the assembly of icosahedral Kaposi's sarcoma-associated herpesvirus
      (KSHV) capsids in insect cells using the baculovirus expression system. Using
      this self-assembly system we investigated whether we could add additional capsid
      associated proteins and determine their incorporation into the assembled capsid.
      We chose the capsid vertex-specific component (CVSC) proteins encoded by open
      reading frames (ORFs) 19 and 32 to test this. This complex sits on the capsid
      vertex and is important for capsid maturation in herpesvirus-infected cells. Co
      immunoprecipitation assays were used to initially confirm a bi-molecular
      interaction between ORF19 and ORF32. Both proteins also precipitated the triplex
      proteins of the capsid shell (ORF26 and ORF62) as well as the major capsid
      protein (ORF25). Capsid immunoprecipitation assays revealed the incorporation of
      ORF19 as well as ORF32 into assembled capsids. Similar experiments also showed
      that the incorporation of each protein occurred independent of the other. These
      studies reveal biochemically how the KSHV CVSC interacts with the capsid shell.

PMID- 28456576
TI  - Influence of the total saponin fraction from Dioscorea nipponica Makino on TLR2/4
      IL1R receptor singnal pathway in rats of gouty arthritis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea nipponica Makino have been extensively
      used in traditional medicine for the treatment of arthritic diseases,
      particularly gouty arthritis (GA). MATERIALS AND METHODS: Sixty male Wistar rats
      were divided into six groups: the normal group, model group, colchicine group
      (COL) and three total saponin groups (RDN) (high dose [160mg/kg], middle dose
      [80mg/kg] and low dose [40mg/kg]). The mRNA and protein expression levels of
      TLR2, TLR4, IRAK1, TRAF6, TAK1, IKKalpha, IkappaBalpha and NF-kappaB in the
      synovial tissue of joint were detected by realtime PCR and WB methods
      respectively. The contents of IL-1beta, IL-6 and TNF-alpha in the blood serum
      were measured by Elisa method. The activation of NF-kappaB was measured by EMSA
      method. RESULTS: Our study showed that RDN decreased both the mRNA and protein
      expressions of TLR2, TLR4, IRAK1, TRAF6, TAK1, IKKalpha, IkappaBalpha and NF
      kappaB of the synovial tissue of joint of rats induced with monosodium urate
      crystal (MSU). They could also reduce the levels of IL-1beta, IL-6 and TNF-alpha
      in the blood serum. Further, EMSA results showed that RDN reduced the DNA binding
      ability of NF-kappaB p65 of model group. CONCLUSION: RDN has the effect of anti
      inflammation in MSU-induced GA model. This is realised by influencing an
      important inflammatory signal pathway which is called TLR2/4-IL1R receptor signal
      pathway. It highlights the potential utility of RDN for the management of GA.

PMID- 28456577
TI  - Evaluation of processed borax as antidote for aconite poisoning.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aconite root is very poisonous; causes cardiac
      arrhythmias, ventricular fibrillation and ventricular tachycardia. There is no
      specific antidote for aconite poisoning. In Ayurveda, dehydrated borax is
      mentioned for management of aconite poisoning. AIM OF THE STUDY: The
      investigation evaluated antidotal effect of processed borax against acute and sub
      acute toxicity, cardiac toxicity and neuro-muscular toxicity caused by raw
      aconite. MATERIALS AND METHODS: For acute protection Study, single dose of
      toxicant (35mg/kg) and test drug (22.5mg/kg and 112.5mg/kg) was administered
      orally, and then 24h survival of animals was observed. The schedule was continued
      for 30 days in sub-acute protection Study with daily doses of toxicant
      (6.25mg/kg), test drug (22.5mg/kg and 112.5mg/kg) and vehicle. Hematological and
      biochemical tests of blood and serum, histopathology of vital organs were carried
      out. The cardiac activity Study was continued for 30 days with daily doses of
      toxicant (6.25mg/kg), test drug (22.5mg/kg), processed borax solution (22.5mg/kg)
      and vehicle; ECG was taken after 1h of drug administration on 1TB, 15th and on
      30th day. For neuro-muscular activity Study, the leech dorsal muscle response to
      2.5ug of acetylcholine followed by response of toxicant at 25ug and 50ug doses
      and then response of test drug at 25ug dose were recorded. RESULTS: Protection
      index indicates that treated borax gave protection to 50% rats exposed to the
      lethal dose of toxicant in acute protection Study. Most of the changes in
      hematological, biochemical parameters and histopathological Study induced by the
      toxicant in sub-acute protection Study were reversed significantly by the test
      drug treatment. The ventricular premature beat and ventricular tachyarrhythmia
      caused by the toxicant were reversed by the test drug indicate reversal of
      toxicant induced cardio-toxicity. The acetylcholine induced contractions in leech
      muscle were inhibited by toxicant and it was reversed by test drug treatment.
      CONCLUSION: The processed borax solution is found as an effective protective
      agent to acute and sub-acute aconite poisoning, and aconite induced cardiac and
      neuro-muscular toxicity. Processed borax at therapeutic dose (22.5mg/kg) has
      shown better antidotal activity profile than five times more than therapeutic
      dose (112.5mg/kg).

PMID- 28456578
TI  - Anti-tumor and chemosensitization effects of Cryptotanshinone extracted from
      Salvia miltiorrhiza Bge. on ovarian cancer cells in vitro.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cryptotanshinone, a natural compound isolated
      from the roots of Salvia miltiorrhiza Bge. (Danshen), is a commonly used
      traditional Chinese medicine to treat high blood pressure in some countries. It
      has been shown that Cryptotanshinone induces cancer cells apoptosis and impairs
      cell migration and invasion. However, the antiproliferation and
      chemosensitization effects of Cryptotanshinone on ovarian cancer and the
      underlying mechanism are not fully elucidated. AIM OF STUDY: In this study, we
      evaluated the inhibitory effect of Cryptotanshinone on ovarian cancer cells and
      explored the underlying molecular mechanism. Additionally, the chemosensitization
      potential of Cryptotanshinone was evaluated in combination with cisplatin.
      MATERIALS AND METHODS: MTT assay was used for cell viability assessment of
      ovarian cancer A2780 cells treated with Cryptotanshinone and/ or cisplatin. Flow
      cytometry was used for apoptosis analysis. Wound healing and transwell assays
      were used for migratory and invasive potential assessment of Cryptotanshinone
      treated ovarian cancer cells. Western blot was used to investigate proteins
      involved in the mechanisms for metastasis and apoptosis. gammaH2AX
      immunocytochemistry was used to detect DNA damage in A2780 cells exposed to
      Cryptotanshinone and/or cisplatin. RESULTS: Cryptotanshinone significantly
      induced ovarian cancer A2780 cells apoptosis by activating caspase cascade.
      Additionally, wound healing and transwell assays revealed that Cryptotanshinone
      could suppress migration and invasion of ovarian cancer cells and dramatically
      inhibited MMP-2 and MMP-9 expression. Furthermore, Cryptotanshinone could
      sensitize A2780 cells to cisplatin treatment in a dose-dependent manner.
      CONCLUSION: Our data confirmed the anti-tumor effect of Cryptotanshinone on
      ovarian cancer cells and provided new findings that Cryptotanshinone could
      sensitize ovarian cancer cells to chemotherapy.

PMID- 28456579
TI  - Exploring the Value of Just-in-Time Teaching as a Supplemental Tool to
      Traditional Resident Education on a Busy Inpatient Pediatrics Rotation.

PMID- 28456580
TI  - Educational Level, Underachievement, and General Mental Health Problems in 10,866
      Adolescents.
AB  - OBJECTIVE: Previous research suggests that cognitive functioning is associated
      with the risk of several adult psychiatric disorders. In this study we
      investigated whether adolescents who perform worse than expected at secondary
      school are at a higher risk for general mental health problems. METHODS: In a
      cross-sectional survey comprising 10,866 Dutch adolescents aged 13 to 16 years,
      underachievement at secondary school was defined as the discrepancy between
      predicted school grade and actual grade 1 or 3 years later. Mental health
      problems were assessed using the Strengths and Difficulties Questionnaire. We
      investigated the association of underachievement with mental health problems
      using logistic regression, adjusting for potential confounders. RESULTS:
      Underachievement was associated with general psychopathology in pupils aged 13 to
      14 years (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.47-2.37) and in
      pupils aged 15 to 16 years (OR, 2.05; 95% CI, 1.67-2.52) in a multivariate
      analysis including sociodemographic factors. The association between
      underachievement and mental health problems was attenuated when school factors
      such as teacher advice and interaction between underachievement and teacher
      advice were added, but underachievement remained significantly associated with
      mental health problems in adolescents in the higher educational tracks (pupils
      aged 13-14 years: OR, 2.22; 95% CI, 1.07-4.60 and OR, 2.41; 95% CI, 1.10-5.30,
      age 15-16 years: OR, 2.63; 95% CI, 1.38-5.03). In the multivariate analysis
      including the interaction between underachievement and teacher advice, a
      significant interaction effect occurs between underachievement and teacher advice
      in the higher tracks. Values of OR and CI are given for each significant
      interaction term. In the younger age group (pupils aged 13-14 years) this results
      in 2 sets of OR and CI. This association was most pronounced for the
      hyperactivity subscale of the Strengths and Difficulties Questionnaire.
      CONCLUSIONS: Underachievement at secondary school is associated with general
      mental health problems, especially with hyperactivity symptoms, in pupils who
      started at high educational tracks.

PMID- 28456581
TI  - Error-related oscillatory activity is modulated by novelty seeking in the reward
      condition.
AB  - Behavioural research has revealed the influence of motivation conditions on
      cognitive task performance and demonstrated that these influences are modulated
      by temperament factors. Modern neuroimaging methods enable analysis of
      neuropsychological mechanisms through which individual differences in
      reinforcement sensitivity may influence cognitive functioning. In the study,
      fifty-six participants were scored on the Cloninger's Temperament and Character
      Inventory to assess punishment and reward sensitivity. Then, subjects
      participated in an EEG experiment using the numerical Stroop task under different
      motivational conditions. In one condition, they were punished for erroneous
      responses; in the other, they were rewarded for correct performance. We analysed
      event related changes in EEG spectral power to investigate the influence of
      temperamentally driven differences on error-related oscillatory brain activity.
      In agreement with previous findings, after incorrect responses an increase in
      frontocentral theta (3-7Hz) and a decrease in occipital alpha (10-11Hz) power
      were observed. Moreover, a multivariate regression analysis showed that these
      spectral markers were modulated by temperamental trait Novelty Seeking in the
      reward condition. To our knowledge, we are the first to demonstrate such a
      relationship between individual differences and error-related oscillatory
      activity. This neuronal pattern may explain why participants that score high on
      Novelty Seeking trait are highly motivated and strongly engaged in a task when a
      reward might be earned. Thus, in conclusion we emphasise that to understand an
      individual's response to errors, it is necessary to account simultaneously for
      motivational conditions as well as temperament traits.

PMID- 28456582
TI  - The role of language similarity in processing second language morphosyntax:
      Evidence from ERPs.
AB  - This study investigated the role of L1-L2 morphosyntactic similarity in L2
      learners of French. In two experiments, we manipulated the grammatical gender
      agreement between an adjective and noun in a sentence context. The noun either
      shared lexical gender across Spanish and French (Experiment 1) or did not
      (Experiment 2). ERPs were collected from beginner Spanish-speaking learners of
      French and native French speakers while they read sentences in French. The
      results for the native speakers revealed a P600 effect on gender agreement
      violations irrespective of lexical gender overlap across languages. L2 learners
      exhibited a negativity in the N400 time window in response to gender agreement
      violations that involved nouns with the same gender in their L1 and L2
      (Experiments 1 and 2), whereas no difference was observed to gender agreement
      violations that involved nouns with contradictory gender across languages
      (Experiment 2). These results suggest that L2 learners at low levels of L2
      proficiency rely on their L1 lexical gender system to detect gender agreement
      errors in L2, but engage different neurocognitive mechanisms to process similar
      L2 morphosyntactic knowledge.

PMID- 28456583
TI  - Protracted development of executive and mnemonic brain systems underlying working
      memory in adolescence: A longitudinal fMRI study.
AB  - Working memory (WM), the ability to hold information on-line to guide planned
      behavior, improves through adolescence in parallel with continued maturation of
      critical brain systems supporting cognitive control. Initial developmental
      neuroimaging studies with one or two timepoints have provided important though
      varied results limiting our understanding of which and how neural systems change
      during this transition into mature WM. In this study, we leverage functional
      magnetic resonance imaging (fMRI) longitudinal data spanning up to 9 years in 129
      normally developing individuals to identify which systems demonstrate growth
      changes that accompany improvements in WM performance. We used a memory guided
      saccade task that allowed us to probe encoding, pure maintenance, and retrieval
      neural processes of WM. Consistent with prior research, we found that WM
      performance continued to improve into the early 20's. fMRI region of interest
      (ROI) analyses revealed developmental (1) increases in sensorimotor-related
      (encoding/retrieval) activity in visual cortex from childhood through early
      adulthood that were associated with WM accuracy and (2) decreases in sustained
      (maintenance) activity in executive regions from childhood through mid
      adolescence that were associated with response latency in childhood and early
      adolescence. Together these results provide compelling evidence that underlying
      the maturation of WM is a transition from reliance on executive systems to
      specialized regions related to the domain of mnemonic requirements of the task
      leading to optimal performance.

PMID- 28456584
TI  - Inference in the age of big data: Future perspectives on neuroscience.
AB  - Neuroscience is undergoing faster changes than ever before. Over 100 years our
      field qualitatively described and invasively manipulated single or few organisms
      to gain anatomical, physiological, and pharmacological insights. In the last 10
      years neuroscience spawned quantitative datasets of unprecedented breadth (e.g.,
      microanatomy, synaptic connections, and optogenetic brain-behavior assays) and
      size (e.g., cognition, brain imaging, and genetics). While growing data
      availability and information granularity have been amply discussed, we direct
      attention to a less explored question: How will the unprecedented data richness
      shape data analysis practices? Statistical reasoning is becoming more important
      to distill neurobiological knowledge from healthy and pathological brain
      measurements. We argue that large-scale data analysis will use more statistical
      models that are non-parametric, generative, and mixing frequentist and Bayesian
      aspects, while supplementing classical hypothesis testing with out-of-sample
      predictions.

PMID- 28456585
TI  - Treating head and neck cancer: for better or for worse?

PMID- 28456586
TI  - The future of personalised radiotherapy for head and neck cancer.
AB  - Radiotherapy has long been the mainstay of treatment for patients with head and
      neck cancer and has traditionally involved a stage-dependent strategy whereby all
      patients with the same TNM stage receive the same therapy. We believe there is a
      substantial opportunity to improve radiotherapy delivery beyond just
      technological and anatomical precision. In this Series paper, we explore several
      new ideas that could improve understanding of the phenotypic and genotypic
      differences that exist between patients and their tumours. We discuss how
      exploiting these differences and taking advantage of precision medicine tools
      such as genomics, radiomics, and mathematical modelling-could open new doors to
      personalised radiotherapy adaptation and treatment. We propose a new treatment
      shift that moves away from an era of empirical dosing and fractionation to an era
      focused on the development of evidence to guide personalisation and biological
      adaptation of radiotherapy. We believe these approaches offer the potential to
      improve outcomes and reduce toxicity.

PMID- 28456587
TI  - Proton therapy for head and neck cancer: expanding the therapeutic window.
AB  - Use of proton beam therapy has expanded, with the number of proton centres
      rapidly increasing not only in the USA but also worldwide. The physical
      characteristics of the proton beam offer important advantages versus widely used
      photon techniques in terms of radiation precision. In head and neck cancer in
      particular, proton beam therapy is uniquely suited for the complex anatomy of
      tumours and sensitive surrounding organs. De-intensification and personalisation
      of treatment to limit toxicity are of renewed importance in the context of human
      papilloma virus-associated disease, in which young patients will be cured but
      bear the consequences of adverse effects for decades. Comparisons of radiation
      dose distributions between photon and proton techniques suggest considerable
      benefit in terms of toxicity sparing, but this has only recently been confirmed
      by substantial clinical data. In this Review, we attempt to define the role of
      this method in the contemporary multidisciplinary management of various types of
      head and neck cancer.

PMID- 28456588
TI  - Potential for low-value palliative care of patients with recurrent head and neck
      cancer.
AB  - Curative treatment for patients with advanced head and neck cancer can be
      associated with many side-effects, and many patients suffer from persistent
      treatment-related side-effects. Patients with recurrent cancer bear the burden of
      these effects along with additional symptoms attributed to the recurrent tumour.
      To better understand the benefits and burden of palliative treatments for
      patients with recurrent head and neck cancer, we reviewed the evidence on
      commonly used palliative treatments and their effect on quality of life. When
      used for palliative care purposes, chemotherapy and radiotherapy have limited
      effectiveness in improving quality of life. Moreover, if these treatments are not
      congruent with a patient's end-of-life goals, they could constitute low-value
      care. We recommend that patients with advanced and recurrent cancer should be
      offered early, comprehensive palliative and supportive services to maximise
      benefit. The principles of beneficence and respect for patients in the context of
      shared decision making must prevail if the trust of this vulnerable patient
      population is to be honoured.

PMID- 28456589
TI  - Management of elderly patients with locoregionally confined head and neck cancer.
AB  - Head and neck cancer in elderly patients represents a major health burden because
      its management provides unique and complex challenges for multidisciplinary
      teams, such as reduced treatment tolerance, multiple comorbidities, and altered
      pharmacokinetics and pharmacodynamics. Despite the prominent challenges involved,
      high-level evidence for the management of this group of patients is scarce.
      Substantial advances in treatment, such as robotic surgery, dynamic intensity
      modulated radiation therapy, immunotherapy, and de-escalation trials, might allow
      for improved treatment tolerance in this patient population. Advanced age alone
      does not appear to be a contraindication to curative treatment. Evaluation of age
      specific factors such as life expectancy, impaired functional status, and
      cognitive decline warrant consideration as part of the management decision
      process. In this Review, we provide an update of the available evidence on the
      management of locoregionally confined head and neck cancer in elderly patients
      and propose a practical treatment algorithm for clinicians to help manage this
      patient population.

PMID- 28456590
TI  - Management of patients with pancreatic cystic lesions: A case-based survey.
AB  - BACKGROUND: Pancreatic cystic lesions (PCL), including intraductal papillary
      mucinous neoplasia (IPMN), harbor different malignant potential and the optimal
      management is often challenging. The present study aims to depict the compliance
      of experts with current consensus guidelines and the accuracy of treatment
      recommendations stratified by the medical specialty and hospital volume. METHODS:
      An international survey was conducted using a set of 10 selected cases of PCL
      that were presented to a cohort of international experts on pancreatology. All
      presented cases were surgically resected between 2004 and 2015 and
      histopathological examination was available. Accuracy of the treatment
      recommendations was based on the European and international consensus guideline
      algorithms, and the histopathological result. RESULTS: The response rate of the
      survey was 26% (46 of 177 contacted experts), consisting of 70% surgeons and 30%
      gastroenterologists/oncologists (GI/Onc). In the case of main-duct IPMN (MD
      IPMN), surgeons preferred more often the surgical approach in comparison with the
      GI/Onc (55 versus 44%). The mean accuracy rate based on the European and
      international consensus guidelines, and the histopathological result, were
      71/76/38% (surgeons), and 70/73/34% (GI/Onc), respectively. High-volume centers
      achieved insignificantly higher accuracy scores with regard to the
      histopathology. Small branch-duct IPMN with cysts <2 cm and malignant potential
      were not identified by the guideline algorithms. CONCLUSION: The survey
      underlines the complexity of treatment decisions for patients with PCL; less than
      40% of the recommendations were in line with the final histopathology in this
      selected case panel. Experts and consensus guidelines may fail to predict
      malignant potential in small PCL.

PMID- 28456591
TI  - Polymorphisms of chemokine receptor genes and clearance of hepatitis C virus
      infection in Chinese population.
AB  - BACKGROUND: Chemokine genes play an essential role in both spontaneous clearance
      in acute infection and therapy of HCV. We investigated whether several CXC family
      related genes associated with HCV spontaneous clearance and response to
      treatment. METHODS: The current study genotyped four SNPs, respectively are CXCR6
      rs2234358, CXCL12 rs1801157, CXCL9 rs10336, rs3733236 to assess their
      associations with HCV spontaneous clearance and response to treatment in a two
      stage study (668 chronic and 400 resolvers in discovery group, meanwhile 333
      chronic and 199 resolver in replication group), and a treatment cohort of HCV
      with 282 patients. RESULTS: We found that the CXCR6 rs2234358 was associated with
      HCV spontaneous clearance in Chinese Han population (dominant model: adjusted
      OR=1.62, 95%CI: 1.30-2.01; additive model: adjusted OR=1.43, 95%CI: 1.20-1.70).
      Patients carrying GT/TT genotypes had increased sustained virological response
      compared with patients carrying the GG genotype (dominant model: adjusted
      OR=2.23, 95%CI: 1.26-3.95). CONCLUSION: These results suggest that CXCR6
      rs2234358 is associated with spontaneous clearance of HCV and response to IFN
      alpha/RBV therapy, which may be identified as a predictive marker in Chinese Han
      population of HCV.

PMID- 28456592
TI  - Whole exome sequencing of sporadic patients with Currarino Syndrome: A report of
      three trios.
AB  - Currarino Syndrome is a rare congenital malformation syndrome described as a
      triad of anorectal, sacral and presacral anomalies. Currarino Syndrome is
      reported to be both familial and sporadic. Familial CS is today known as an
      autosomal dominant disorder caused by mutations in the transcription factor MNX1.
      The aim of this study was to look for genetic causes of Currarino Syndrome in
      sporadic patients after ruling out other causes, like chromosome aberrations,
      disease-causing variants in possible MNX1 cooperating transcription factors and
      aberrant methylation in the promoter of the MNX1 gene. The hypothesis was that
      MNX1 was affected through interactions with other transcription factors or
      through other regulatory elements and thereby possibly leading to abnormal
      function of the gene. We performed whole exome sequencing with an additional 6Mb
      custom made region on chromosome 7 (GRCh37/hg19, chr7:153.138.664-159.138.663) to
      detect regulatory elements in non-coding regions around the MNX1 gene. We did not
      find any variants in genes of interest shared between the patients. However,
      after analyzing the whole exome sequencing data with Filtus, the in-house SNV
      filtration program, we did find some interesting variants in possibly relevant
      genes that could be explaining these patients' phenotypes. The most promising
      genes were ETV3L, ARID5A and NCAPD3. To our knowledge this is the first report of
      whole exome sequencing in sporadic CS patients.

PMID- 28456593
TI  - The role of miR-372 in ovarian carcinoma cell proliferation.
AB  - OBJECTIVES: MicroRNA-372 has been shown to be associated with multiple tumors'
      development and progression, by regulating the expression of proteins involved in
      cell cycle and apoptosis. However, the specific mechanism and function of miR-372
      in ovarian carcinoma are not clear. Our study explored the role of miR-372 in
      ovarian carcinoma cell cycle and proliferation. MATERIALS AND METHODS: MiR-372
      expression was quantified in normal ovarian tissue, benign tumors, primary
      ovarian carcinomas and metastatic omentum by qRT-PCR. MTT assay and plate clone
      formation assay were performed to evaluate the cell viability and proliferation.
      EDU assay and cell apoptosis assay were also used to determine cell growth. We
      used Western Blot to analysis expression of the known miR-372 targets. RESULTS:
      We found that miR-372 expression was significantly lower in ovarian carcinoma
      than normal ovarian tissues and benign tumors. Moreover, miR-372 overexpression
      showed significant inhibition of cell proliferation and promoted cell apoptosis.
      Western Blot revealed that miR-372 downregulated the expression of ATAD2, LATS2,
      P62, DKK1 and cyclinA1 to inhibit the proliferation of cells. CONCLUSIONS: Our
      findings indicate that miR-372 has a prominent role in inhibiting tumor growth
      and it is a valuable target for ovarian cancer therapy.

PMID- 28456594
TI  - The association of eight potentially functional polymorphisms in five adrenergic
      receptor-encoding genes with myocardial infarction risk in Han Chinese.
AB  - Adrenergic receptors play a key role in activating the sympathetic nervous
      system, which often accompanies with the development of myocardial infarction
      (MI). Here, we aimed to test the association of eight potentially functional
      polymorphisms in five adrenergic receptor-encoding genes with MI risk. Genotypes
      were available for 717 MI patients and 612 controls. There were no detectable
      deviations from the Hardy-Weinberg equilibrium for all study polymorphisms.
      Allele frequencies differed remarkably for ADRA2B D/I (P<0.001), ADRB1 Ser49Gly
      (P=0.002), ADRB2 Gln27Glu (P=0.005), and ADRB3 Trp64Arg (P<0.001) polymorphisms,
      even after the Bonferroni correction. Systolic blood pressure was significantly
      lower in ADRA2B II genotype carriers than in the DD genotype carriers (P=0.006),
      while plasma high-density lipoprotein cholesterol was significantly higher in
      patients carrying ADRA2B I allele and ADRB1 49Ser allele than in patients with
      the DD genotype and 49Gly/49Gly genotype, respectively (P=0.018 and 0.033).
      Overall best interaction model consisted of ADRA2B D/I, ADRB1 Ser49Gly,
      dyslipidemia and hypertension, with the highest testing accuracy of 0.627 and the
      maximal 10-fold cross-validation consistency (P=0.017). Finally, a nomogram was
      depicted based on four significant polymorphisms and metabolic risk factors, and
      it had a better predictive utility and was internally validated with a
      discrimination C-index of 0.723 (P<0.001). Altogether, we identified two
      polymorphisms, ADRA2B D/I and ADRB1 Ser49Arg, which not only altered genetic
      susceptibility to MI, but also impacted on blood pressure and plasma lipid
      changes, and their combination with metabolic risk factors constituted the
      overall best interaction model.

PMID- 28456596
TI  - Mapping the Workload Associated with Intact Abdominal Aortic Aneurysm.

PMID- 28456595
TI  - CFTR gene mutations and polymorphism are associated with non-obstructive
      azoospermia: From case-control study.
AB  - A variety of experimental studies have yielded evidence that the cystic fibrosis
      transmembrane conductance regulator (CFTR) protein participates in the process of
      spermatogenesis. However, the association between CFTR gene and non-obstructive
      azoospermia (NOA) disease remained to be a question. First, we reviewed available
      data from the PubMed and Embase databases before May 2016 to find the most common
      mutations of CFTR gene in NOA patients. Second, an original case-control study
      was conducted on NOA patients (n=100) and a control group consisting of fertile
      males (n=100), selected from August 2015 to March 2017, to detect CFTR gene
      mutations and polymorphism. Peripheral blood samples from NOA patients and normal
      controls were analyzed for the presence of specific sequences of CFTR gene by
      polymerase chain reaction amplification followed by direct sequencing. From our
      comprehensive review, 12 case-control studies were found concerning the relation
      between CFTR gene mutations and polymorphism and NOA disease. Fifty-four
      mutations were mentioned and IVS8 poly-T, TG repeats, F508del and R117H mutations
      were the most common ones. Based on that, we detected IVS8 poly-T, TG repeats,
      F508del, R117H and M470V mutations in our case control study. We found that the
      T5 allele was present at a significantly higher rate in NOA patients than in the
      control group (5.00% versus 0.00%, p<0.01) with increased risk having NOA [Odds
      ratios (OR) 2.05, 95% confidence intervals (CI) 1.85-2.27]. The T5 variant was
      always accompanied by TG12 (10/10) and V470 allele participated in most TG12T5
      haplotypes (8/10). TG12T5-V470 haplotype also enhanced risk of having NOA [OR
      2.04, 95% CI 1.84-2.26]. F508del and R117H mutations were not found in either
      group. In conclusion, the polyvariant mutant genes of CFTR: T5 allele and TG12-T5
      V470 genotype are correlated with NOA, but F508del and R117H mutations have low
      possibility to be associated with NOA.

PMID- 28456597
TI  - Associations of Giardia lamblia assemblages with HIV infections and
      symptomatology: HIV virus and assemblage B were they born to each other?
AB  - Giardia lamblia is an intestinal parasite that has an extensive genetic variation
      among isolates. This species is divided into eight different assemblages (A-H),
      but only assemblages A and B have been associated with human infections. Studies
      on the associations of G. lamblia assemblages and symptoms have been done but
      were inconclusive. The aim of this study was to correlate G. lamblia assemblages
      with symptoms in patients with and without HIV/AIDS and its association with the
      CD4T cell count. The cross-sectional survey was conducted among patients
      attending the Evandro Chagas National Institute of Infectious Diseases
      (INI/FIOCRUZ) in Rio de Janeiro from January 2011 to February 2015. Thirty-eight
      of 65 microscopically positive stool samples for G. lamblia were from HIV
      positive patients and 27 were from HIV negative patients. Of the HIV infected
      patients, 19 (55.9%) were genotyped as assemblage B of which 9 (47.4%) had a
      CD4Tcell count below 200cells/mm3. In addition, we found a greater number of
      samples belonging to assemblage B in symptomatic cases (11 of 19; 57.9%). Our
      data suggest that assemblage B is very likely to be found in HIV infected
      patients and probably the lower CD4T count gives advantages for assemblage B
      replication. Furthermore, assemblage B seems to be associated with
      symptomatology, particularly abdominal pain, asthenia, diarrhea, fever, headache
      and myalgia. This study provides information on G. lamblia assemblages and
      symptoms in patients with and without HIV/AIDS virus and their association with
      CD4Tcell counts.

PMID- 28456598
TI  - Two haplotype clusters of Echinococcus granulosus sensu stricto in northern Iraq
      (Kurdistan region) support the hypothesis of a parasite cradle in the Middle
      East.
AB  - Human cystic echinococcosis (CE) caused by Echinococcus granulosus s.s. is a
      major public health problem in Iraqi Kurdistan with a reported surgical incidence
      of 6.3 per 100,000 Arbil inhabitants. A total of 125 Echinococcus isolates
      retrieved from sheep, goats and cattle were used in this study. Our aim was to
      determine species/genotypes infecting livestock in Iraqi Kurdistan and examine
      intraspecific variation and population structure of Echinococcus granulosus s.s.
      in this region and relate it to that of other regions worldwide. Using nucleotide
      sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox 1) we
      identified E. granulosus s.s. as the cause of hydatidosis in all examined
      animals. The haplotype network displayed a double-clustered topology with two
      main E. granulosus s.s. haplotypes, (KU05) and (KU33). The 'founder' haplotype
      (KU05) confirmed the presence of a common lineage of non-genetically
      differentiated populations as inferred by the low non-significant fixation index
      values. Overall diversity and neutrality indices indicated demographic expansion.
      We used E. granulosus s.s. nucleotide sequences from GenBank to draw haplotype
      networks for the Middle East (Iran, Jordan and Turkey), Europe (Albania, Greece,
      Italy, Romania and Spain), China, Mongolia, Russia, South America (Argentina,
      Brazil, Chile and Mexico) and Tunisia. Networks with two haplotype clusters like
      that reported here for Iraqi Kurdistan were seen for the Middle East, Europe,
      Mongolia, Russia and Tunisia using both 827bp and 1609bp cox1 nucleotide
      sequences, whereas a star-like network was observed for China and South America.
      We hypothesize that the double clustering seen at what is generally assumed to be
      the cradle of domestication may have emerged independently and dispersed from the
      Middle East to other regions and that haplotype (KU33) may be the main haplotype
      within a second cluster in the Middle East from where it has spread into Europe,
      Mongolia, Russia and North Africa. Further studies using metacestodes of human
      origin are required to investigate the biological importance of E. granulosus
      s.s. haplotypes/clusters and their association, if any with clinical
      manifestations of CE infection.

PMID- 28456599
TI  - Robotically Assisted Minimally Invasive Off-Pump Coronary Artery Bypass Surgery
      in a Patient With Permanent Tracheostomy.
AB  - BACKGROUND: Patients with a permanent tracheostomy requiring coronary surgery
      represent a unique challenge, being at increased risk of sternal wound
      complications, mediastinitis and stoma necrosis. Several techniques have been
      described including manubrium sparing sternotomy, thoracoscopic internal mammary
      harvest and hybrid revascularisation. METHODS: We report a case of robotic
      assisted (daVinci(r)XiTM Surgical System) total arterial off-pump
      revascularisation in a patient with previous laryngectomy and permanent
      tracheostomy. The main advantage of this approach was to minimise the risk of
      postoperative sternal complication and mediastinatis, whilst still providing the
      prognostic benefit of total arterial grafting and the neurological advantage of
      the aorta no-touch technique.

PMID- 28456600
TI  - Beliefs in the population about cracking sounds produced during spinal
      manipulation.
AB  - OBJECTIVES: To examine beliefs about cracking sounds heard during high-velocity
      low-amplitude (HVLA) thrust spinal manipulation in individuals with and without
      personal experience of this technique. METHODS: We included 100 individuals.
      Among them, 60 had no history of spinal manipulation, including 40 who were
      asymptomatic with or without a past history of spinal pain and 20 who had
      nonspecific spinal pain. The remaining 40 patients had a history of spinal
      manipulation; among them, 20 were asymptomatic and 20 had spinal pain.
      Participants attended a one-on-one interview during which they completed a
      questionnaire about their history of spinal manipulation and their beliefs
      regarding sounds heard during spinal manipulation. RESULTS: Mean age was 43.5+/
      15.4years. The sounds were ascribed to vertebral repositioning by 49% of
      participants and to friction between two vertebras by 23% of participants; only
      9% of participants correctly ascribed the sound to the formation of a gas bubble
      in the joint. The sound was mistakenly considered to indicate successful spinal
      manipulation by 40% of participants. No differences in beliefs were found between
      the groups with and without a history of spinal manipulation. CONCLUSIONS:
      Certain beliefs have documented adverse effects. This study showed a high
      prevalence of unfounded beliefs regarding spinal manipulation. These beliefs
      deserve greater attention from healthcare providers, particularly those who
      practice spinal manipulation.

PMID- 28456601
TI  - Do we need animal models to advance research on inflammatory joint disease?

PMID- 28456602
TI  - An update on nitric oxide and its benign role in plant responses under metal
      stress.
AB  - Pollution due to heavy metal(loid)s has become common menace across the globe.
      This is due to unprecedented frequent geological changes coupled with increasing
      anthropogenic activities, and population growth rate. Heavy metals (HMs) presence
      in the soil causes toxicity, and hampers plant growth and development. Plants
      being sessile are exposed to a variety of stress and/or a network of different
      kinds of stresses throughout their life cycle. To sense and transduce these
      stress signal, the signal reactive nitrogen species (RNS) particularly nitric
      oxide (NO) is an important secondary messenger next to only reactive oxygen
      species (ROS). Nitric oxide, a redox active molecule, colourless simple gas, and
      being a free radical (NO) has the potential in regulating multiple biological
      signaling responses in a variety of plants. Nitric oxide can counteract HMs
      induced ROS, either by direct scavenging or by stimulating antioxidants defense
      team; therefore, it is also known as secondary antioxidant. The imbalance or
      cross talk of/between NO and ROS concentration along with antioxidant system
      leads to nitrosative and oxidative stress, or combination of both i.e., nitro
      oxidative stress. Endogenous synthesis of NO also takes place in plants in the
      presence of heavy metals. During HM stress the different organelles of plant
      cells can biosynthesize NO in parallel to the ROS, such as in mitochondria,
      chloroplasts, peroxisomes, cytoplasm, endoplasmic reticulum and apoplasts. In
      view of the above, an effort has been made in the present review article to trace
      current knowledge and latest advances in chemical properties, biological roles,
      mechanism of NO action along with the physiological, biochemical, and molecular
      changes that occur in plants under different metal stress. A brief focus is also
      carried on ROS properties, roles, and their production.

PMID- 28456603
TI  - Does systemic lidocaine reduce ketamine requirements for endotracheal intubation
      in calves?
AB  - OBJECTIVE: To investigate whether an intravenous (IV) lidocaine bolus in calves
      premedicated with xylazine-butorphanol reduces the amount of ketamine required to
      allow endotracheal intubation. STUDY DESIGN: Randomized, prospective clinical
      study. ANIMALS: In total, 41 calves scheduled for elective umbilical surgery.
      METHODS: Calves were randomly assigned to one of two groups (L: lidocaine or S:
      saline). The calves were administered xylazine (0.07 mg kg-1) and butorphanol
      (0.1 mg kg-1) intramuscularly and 10 minutes later lidocaine (2 mg kg-1; group L)
      or saline (group S) IV over 1 minute. After 2 minutes, ketamine (2.5 mg kg-1) was
      injected IV. If the depth of anaesthesia was insufficient for intubation,
      additional ketamine (1 mg kg-1) was administered every minute until intubation
      was successful. The amount of ketamine required for intubation, respiratory rate,
      pulse rate, arterial pressures, the depth of sedation and conditions of
      endotracheal intubation after induction of anaesthesia were compared between the
      two groups. RESULTS: The calves in group L were sedated more deeply than those in
      group S; however, neither the median (range) amount of ketamine required for
      intubation, 3.5 (2.5-4.5) mg kg-1 and 3.5 (2.5-3.5) mg kg-1, respectively, nor
      the induction quality differed significantly between the groups. CONCLUSION AND
      CLINICAL RELEVANCE: A bolus of lidocaine (2 mg kg-1) administered 10 minutes
      after xylazine-butorphanol in calves deepened the degree of sedation but did not
      decrease the requirement of ketamine for endotracheal intubation. No adverse
      effects were recorded in the physiological variables measured.

PMID- 28456604
TI  - Herpesviruses hijack host exosomes for viral pathogenesis.
AB  - Herpesviruses are remarkable pathogens possessing elaborate mechanisms to seize
      various host cellular components for immune evasion, replication, and virion
      egress. As viruses are dependent upon their hosts, investigating this intricate
      interplay has revealed that the exosome pathway is utilised by alpha (Herpes
      Simplex Virus 1), beta (Human Cytomegalovirus, and Human Herpesvirus 6) and gamma
      (Epstein-Barr Virus, and Kaposi Sarcoma-associated Herpesvirus) herpesviruses.
      Virions and exosomes share similar properties and functions. For example,
      exosomes are small membranous nanovesicles (30-150nm) released from cells that
      contain proteins, DNA, and various coding and non-coding RNA species. Given
      exosomes can shuttle various molecular cargo from a donor to recipient cell, they
      serve as important vehicles facilitating cell-cell communication. Therefore,
      exploitation by herpesviruses impacts several aspects of infection including: i)
      acquisition of molecular machinery for secondary envelopment and viral assembly,
      ii) export of immune-related host proteins from infected cells, iii) enhancing
      infection in surrounding cells via transfer of viral proteins, mRNA and miRNA,
      and iv) regulation of viral protein expression to promote persistence. Studying
      the dichotomy that exists between host exosomes and herpesviruses has two
      benefits. Firstly, it will reveal the precise pathogenic mechanisms viruses have
      evolved, generating knowledge for antiviral development. Secondly, it will shed
      light upon fundamental exosome characteristics that remain unknown, including
      cargo selection, protein trafficking, and non-canonical biogenesis.

PMID- 28456605
TI  - Optimizing electrostatic interactions for controlling the release of proteins
      from anionic and cationically modified alginate.
AB  - Alginate and cationically modified alginate microparticles were prepared with the
      goal of developing hydrogel microparticles that offer controlled release of
      protein drugs mainly by modification of the absolute charge of the hydrogel
      network. Protein loading and release studies were carried out using model
      proteins with different net charges (i.e. low, high, and neutral isoelectric
      points) covering a broad range of molecular weights. The Projection to Latent
      Structures (PLS) method was used for qualitatively and quantitatively describing
      the relationships between the properties of proteins such as net charge and
      molecular weight, polymer properties including degree of substitution and
      microparticle size, and the release kinetics (ktn). It was found that
      electrostatic interactions and protein molecular weight had the greatest impact
      on parameter k while parameter n was mostly affected by polymer and buffer
      properties. In addition to understanding the current trends, the multivariate
      statistical method also provided an effective and reliable model as a beneficial
      tool for predicting and optimizing protein delivery systems.

PMID- 28456606
TI  - Cyclodextrin-based nanosponges for the targeted delivery of the anti-restenotic
      agent DB103: A novel opportunity for the local therapy of vessels wall subjected
      to percutaneous intervention.
AB  - Nano-sized colloidal carriers represent innovative drug delivery systems, as they
      allow a targeted and prolonged release of poorly water-soluble drugs, improving
      their bioavailability and modifying their pharmacokinetic parameters. In this
      work we describe cyclodextrin-based nanosponges, obtained through polimerization
      of beta-cyclodextrin with diphenyl carbonate as the cross-linking agent, loaded
      with a novel multi-effective heterocyclic compound, DB103, able to regulate key
      cellular events involved in the remodelling of vessels wall. Fabrication and drug
      loading procedures, as well as physical-chemical characterization and drug
      release profile of the novel colloidal system are reported. Results achieved
      demonstrate the ability of nanosponges to enclose efficiently the target drug and
      release it slowly and continuously, thus suggesting the exploitability of the
      novel system for the local therapy of vessels wall subjected to percutaneous
      intervention.

PMID- 28456607
TI  - Multi-locus phylogenetic analysis of the genus Limnodrilus (Annelida: Clitellata:
      Naididae).
AB  - Limnodrilus species are annelid worms distributed worldwide in various freshwater
      sediments. The systematics of Limnodrilus has chiefly been based on morphology,
      but the genus has not been subject to any closer phylogenetic studies over the
      past two decades. To reconstruct the evolutionary history of Limnodrilus, and to
      assess the monophyly of this genus and its systematic position within the
      subfamily Tubificinae (Annelida: Clitellata: Naididae), 45 Limnodrilus specimens,
      representing 19 species, and 35 other naidid species (representing 24 genera)
      were sampled. The data consisted of sequences of three mitochondrial genes (COI,
      12S and 16S rDNA) and four nuclear markers (18S and 28S rDNA, Histone 3, and
      ITS). The phylogeny was estimated, using Maximum Likelihood and Bayesian analyses
      of concatenated data of seven DNA loci, as well as a multi-locus coalescent-based
      approach. All analyses strongly suggest that Limnodrilus is monophyletic, but
      only if the morphospecies L. rubripenis is removed from it. Limnodrilus
      rubripenis and (at least) Baltidrilus, Lophochaeta and some species attributed to
      Varichaetadrilus comprise the sister group to the clade Limnodrilus sensu
      stricto, and the latter is further divided into three well-supported groups. One
      of them contains morphospecies characterized by short cuticular penis sheaths and
      enlarged chaetae in anterior segments (L. udekemianus, L. silvani and L.
      grandisetosus). The second is a small group of species with moderately long penis
      sheaths, i.e., L. sulphurensis and L. profundicola. The third, and largest group,
      includes not only the multitude of cryptic species in the L. hoffmeisteri
      complex, but also other, morphologically distinct, species nested within this
      complex. All studied species in this large group have long penis sheaths, which
      are exceptionally long in L. claparedianus, L. maumeensis, and a form
      morphologically intermediate between L. claparedianus and L. cervix. The
      identification and classification of these groups provide a framework for
      directed sampling in further phylogenetic studies, and for revisionary work on
      the L. hoffmeisteri complex and other unresolved Limnodrilus species.

PMID- 28456608
TI  - Chronic intermittent hypoxia worsens bleomycin-induced lung fibrosis in rats.
AB  - Obstructive sleep apnea (OSA) has been linked to increased mortality in pulmonary
      fibrosis. Its key feature, chronic intermittent hypoxia (CIH), can lead to
      oxidative stress and inflammation, known to lead to fibrotic pathology in other
      organs. We tested the effects of CIH in an animal model of bleomycin-induced lung
      fibrosis. Sprague Dawley rats were instilled intratracheally with bleomycin (Blm)
      or saline (Sal), and exposed to CIH or normal air (Norm) for 9 or 30 days.
      Pulmonary function was tested and lungs were harvested for histological and
      molecular analyses. In Blm-treated animals, 30days of CIH compared to Norm
      increased total lung collagen content (p=0.008) and reduced Quasi-static lung
      compliance (p=0.04). CIH upregulated lipid peroxidation and increased NF-kappaB
      activation, IL-17 mRNA and Col1alpha1 mRNA expression. Our results indicate that
      following Blm-induced lung injury, CIH amplifies collagen deposition via
      oxidative and inflammatory pathways, culminating in stiffer lungs. Thus, OSA may
      augment fibrosis in patients with interstitial lung disease.

PMID- 28456609
TI  - Computational modeling for cardiac safety pharmacology analysis: Contribution of
      fibroblasts.
AB  - INTRODUCTION: Drug-induced proarrhythmic potential is an important regulatory
      criterion in safety pharmacology. The application of in silico approaches to
      predict proarrhythmic potential of new compounds is under consideration as part
      of future guidelines. Current approaches simulate the electrophysiology of a
      single human adult ventricular cardiomyocyte. However, drug-induced proarrhythmic
      potential can be different when cardiomyocytes are surrounded by non-muscle
      cells. Incorporating fibroblasts in models of myocardium is important
      particularly for predicting a drugs cardiac liability in the aging population - a
      growing population who take more medications and exhibit increased cardiac
      fibrosis. In this study, we used computational models to investigate the effects
      of fibroblast coupling on the electrophysiology and response to drugs of
      cardiomyocytes. METHODS: A computational model of cardiomyocyte electrophysiology
      and ion handling (O'Hara, Virag, Varro, & Rudy, 2011) is coupled to a passive
      model of fibroblast electrophysiology to test the effects of three compounds that
      block cardiomyocyte ion channels. Results are compared to model results without
      fibroblast coupling to see how fibroblasts affect cardiomyocyte action potential
      duration at 90% repolarization (APD90) and propensity for early after
      depolarization (EAD). RESULTS: Simulation results show changes in cardiomyocyte
      APD90 with increasing concentration of three drugs that affect cardiac function
      (dofetilide, vardenafil and nebivolol) when no fibroblasts are coupled to the
      cardiomyocyte. Coupling fibroblasts to cardiomyocytes markedly shortens APD90.
      Moreover, increasing the number of fibroblasts can augment the shortening effect.
      DISCUSSION: Coupling cardiomyocytes and fibroblasts are predicted to decrease
      proarrhythmic susceptibility under dofetilide, vardenafil and nebivolol block.
      However, this result is sensitive to parameters which define the
      electrophysiological function of the fibroblast. Fibroblast membrane capacitance
      and conductance (CFB and GFB) have less of an effect on APD90 than the fibroblast
      resting membrane potential (EFB). This study suggests that in both theoretical
      models and experimental tissue constructs that represent cardiac tissue, both
      cardiomyocytes and non-muscle cells should be considered when testing cardiac
      pharmacological agents.

PMID- 28456610
TI  - Sexual Function, Obesity, and Weight Loss in Men and Women.
AB  - INTRODUCTION: Obesity is a major health concern in the United States and many
      developed countries. Among its many deleterious effects are those that can affect
      the sexual response. AIM: To update and evaluate the state of knowledge on the
      possible link between obesity and sexual dysfunction. METHODS: A comprehensive
      search and review of biomedical, physiologic, and psychological databases were
      used to integrate findings on obesity, weight loss, and sexual function. MAIN
      OUTCOME MEASURES: We briefly explain the two variables of interest-sexual
      functioning and obesity-indicating possible points of linkage. Then, we attempt
      to (i) describe possible direct links between obesity and sexual dysfunction;
      (ii) understand potential mediating biological, comorbid, and psychological
      factors and the interactions among such factors; (iii) discern differences in the
      mechanism and impact of obesity across the sexes; and (iv) review evidence
      suggesting that weight loss improves sexual functioning in obese individuals.
      RESULTS: The link between obesity and sexual function is complex and
      multivariate, with at least three different pathways likely: direct effects from
      adipose tissue; effects from pathophysiologic comorbidities; and effects mediated
      by psychological factors. In addition, effects and pathways appear to be
      different for men and women. CONCLUSION: We conclude by identifying some existing
      challenges for the study of obesity and sexual function, specify areas that
      warrant further investigation, and reiterate the potential value of encouraging
      obese patients to consider weight loss as a path toward a healthier and more
      sexually satisfying life. Rowland DL, McNabney SM, Mann AR. Sexual Function,
      Obesity, and Weight Loss in Men and Women. Sex Med Rev 2017;5:323-338.

PMID- 28456611
TI  - Increased risk of PTLD in lung transplant recipients with cystic fibrosis.
AB  - BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is an important
      cause of morbidity and mortality following lung transplantation. Recipients with
      cystic fibrosis (CF) may have an increased risk of PTLD although the literature
      is limited to single center cohorts. Our primary aim is to examine PTLD in an
      adult lung transplant population by utilizing the International Society for Heart
      and Lung Transplantation Registry. METHODS: We studied 30,598 adult recipients of
      lung transplants performed between 1999 and 2011. The primary outcome was
      development of and time to PTLD. In addition to indication for transplant, other
      predictors examined included Epstein-Barr virus (EBV) and cytomegalovirus (CMV)
      serostatus, gender, and age. Outcomes were assessed with univariable and
      multivariable Cox proportional hazard models to obtain hazard ratios (HR).
      RESULTS: 17% of the cohort had a diagnosis of CF. PTLD developed in 2% of CF
      recipients compared to 1% for non-CF recipients (p<0.001). Compared to non-CF
      recipients, CF recipients had higher prevalence of EBV and CMV seronegativity and
      higher prevalences of high risk EBV and CMV mismatch (D+/R-). There is a
      significant association between CF and the development of PTLD [HR 1.66 (95% CI
      1.30-2.12)]. Stratified multivariable analysis controlling for age revealed EBV
      negative non-CF recipients have an almost 2 fold increased risk of developing
      PTLD, whereas EBV negative CF recipients had an almost 6.5 fold increased risk.
      CONCLUSIONS: CF recipients have a higher risk for PTLD compared to non-CF
      recipients. Further studies are needed to account for additional risk factors and
      management in this population post-transplant.

PMID- 28456612
TI  - Experimental Laminin 332 Mucous Membrane Pemphigoid Critically Involves C5aR1 and
      Reflects Clinical and Immunopathological Characteristics of the Human Disease.
AB  - Mucous membrane pemphigoid is an autoantibody-mediated disease predominantly
      affecting the oral cavity, pharynx, and conjunctiva. Conjunctival lesions may
      lead to impaired vision and, finally, blindness. About 25% of mucous membrane
      pemphigoid patients generate autoantibodies against the alpha3 chain of laminin
      332 (LAMalpha3), a structural protein of epidermal/epithelial basement membranes.
      Here, we established a mouse model by the passive transfer of rabbit IgG against
      the murine homologs of two immunodominant fragments in adult C57BL/6 mice
      (mLAMalpha3). After repeated subcutaneous injections of anti-mLAMalpha3 IgG
      erosions and crusts occurred predominantly around the snout, eyes, and on ears.
      Conjunctival and oral/pharyngeal lesions with subepithelial splitting were found
      in 80% and 100% of mice, respectively. In contrast, disease development was
      abrogated in FcRgamma chain-deficient mice and markedly reduced in C5aR1
      deficient mice. Furthermore, wild-type mice injected with anti-mLAMalpha3 F(ab')2
      were completely protected. Our findings suggest a crucial codominant role of
      FcRgamma and complement activation of the anti-mLAMalpha3 IgG-induced mouse model
      of mucous membrane pemphigoid. This model will help further discover the
      pathomechanisms of this devastating disease. Furthermore, it may be of use to
      explore the effect of urgently needed more specific anti-inflammatory mediators
      on mucosal and skin lesions in autoantibody-mediated diseases.

PMID- 28456613
TI  - E-Cadherin-Mediated Cell Contact Controls the Epidermal Damage Response in
      Radiation Dermatitis.
AB  - Radiotherapy is a primary oncological treatment modality that also damages normal
      tissue, including the skin, and causes radiation dermatitis (RD). Here, we
      explore the mechanism of acute epidermal damage in radiation dermatitis. Two
      distinctive phases in the damage response were identified: an early destructive
      phase, where a burst of reactive oxygen species induces loss of E-cadherin
      mediated cell contact, followed by a regenerative phase, during which Wnt and
      Hippo signaling are activated. A blocking peptide, as well as a neutralizing
      antibody to E-cadherin, works synergistically with ionizing radiation to promote
      the epidermal damage. In addition, ROS disassembles adherens junctions in
      epithelial cells via posttranslational mechanisms, that is, activation of Src/Abl
      kinases and degradation of beta-catenin/E-cadherin. The key role of tyrosine
      kinases in this process is further substantiated by the rescue effect of the
      tyrosine kinase inhibitor genistein, and the more specific Src/Abl kinase
      inhibitor dasatinib: both reduced ROS-induced degradation of beta-catenin/E
      cadherin in vitro and ameliorated skin damage in rodent models. Finally, we
      confirm that the same key molecular events are also seen in human radiation
      dermatitis. Therefore, we propose that loss of cell contact in epidermal
      keratinocytes through reactive oxygen species-mediated disassembly of adherens
      junctions is pivotal for the acute epidermal damage in radiation dermatitis.

PMID- 28456614
TI  - Healthcare provider perceptions of accessible exam tables in primary care:
      Implementation and benefits to patients with and without disabilities.
AB  - BACKGROUND: Recent healthcare mandates require availability of accessible medical
      exam equipment, which may reduce barriers to care for patients with disabilities
      (PWD). However, more research is needed to explore healthcare provider views on
      implementation and routine use of accessible equipment. OBJECTIVE: This study
      qualitatively explored healthcare provider perceptions of: (1) daily use of
      accessible medical examination tables with PWD; and (2) recommendations for
      addressing challenges to using this equipment. METHODS: Qualitative interviews
      and focus groups were conducted with physicians, nurse practitioners and
      registered nurses at a clinic where accessible examination tables were recently
      implemented in all clinic rooms. Data were coded and thematically analyzed by two
      researchers trained in qualitative methods. RESULTS: A total of 17 providers
      participated in focus groups or interviews. Participants were mostly female (82%;
      N = 14), and registered nurses (47%; N = 8), but also included nurse
      practitioners (29.4%; N = 5), and physicians (23%; N = 4). Common themes were:
      (1) Ease of use and functionality of tables; and (2) Challenges with use and
      available training. Overall, providers reported satisfaction with the tables'
      ability to accommodate patients who are PWD, although they expressed challenges
      with functionally using the tables with specific populations, such as pediatric
      patients. CONCLUSIONS: Healthcare organizations seeking to implement height
      adjustable tables should account for structural requirements of the height
      adjustable tables (e.g. accommodating clearance needed when planning room sizes).
      Practical recommendations and policies for integrating height-adjustable tables
      into routine clinical care are needed to ensure equitable care for PWD.

PMID- 28456615
TI  - A pilot study of Trabajadora de salud, a lay health worker intervention for
      Latinas/os with traumatic brain injuries and their caregivers.
AB  - BACKGROUND: Latinas/os with traumatic brain injuries (TBIs) and their caregivers
      experience worse outcomes than others. OBJECTIVE: The study aimed to assess the
      acceptability and promise of Trabajadora de Salud on the functional abilities,
      hospital readmission, rehabilitation, employment, depression, somatic symptoms,
      and caregiver burden among Latinas/os with TBIs and their caregivers. METHODS: A
      pre-posttest experimental pilot study was conducted. A total of eight Latina/o
      adult patients (50% female) with mild or moderate TBI and six of their caregivers
      (66.7% female) were randomized to receive Trabajadora de Salud or a telephone
      only control group. Trabajadora de Salud, a three-month, in-home intervention
      administered by bilingual lay health workers, focused on: 1) providing empathy
      and validation of TBI symptoms, 2) addressing basic needs, 3) goal setting, and
      4) improving communication with healthcare providers. RESULTS: Trabajadora de
      Salud was widely accepted by patients, caregivers, and health professionals. The
      functional, depression, and somatic symptoms of the patients as well as the
      somatic symptoms and caregiver burden of the caregivers improved more for
      participants in the intervention group than the control group. CONCLUSIONS:
      Trabajadora de Salud demonstrated promise in improving outcomes of Latinas/os
      with TBIs and their caregivers and should be further studied.

PMID- 28456616
TI  - Actions of SPM in regulating host responses in arthritis.
AB  - The discovery and identification of omega-3 fatty acid derived specialized pro
      resolving mediators (SPM) provides a molecular mechanism for the beneficial
      effects of fish oil supplementation in patients suffering from arthritis. Here we
      review the plethora of bioactions of SPM in the context of joint diseases,
      focusing on both cellular targets and molecular mechanisms. Whenever possible, a
      parallel to clinical and preclinical data produced with fish oil supplementation
      is made to strengthen the mechanistic link between omega-3 fatty acids and SPM
      biosynthesis. SPM can modulate the reactivity of many cells that are pivotal to
      the development and/or maintenance of joint disease. Whereas work has so far
      focused on the actions of SPM on immune cells and therefore, within this context,
      macrophages, neutrophils, mast cells and T cells, we reason that more work needs
      to focus on the effects that these bioactive lipid mediators may have on the
      structural cell component of the joint, this encompassing synovial fibroblasts,
      chondrocytes, osteoclasts and osteoblasts. Full definition of the properties that
      SPM may exert on these cells can help in unveiling their ability to promote
      tissue restoration and regeneration, a prerequisite to repair joint damage, and
      as such promote the development of innovative therapeutic strategies based on the
      science of SPM and resolution.

PMID- 28456617
TI  - Laparoscopic Excision Versus Ablation for Endometriosis-associated Pain: An
      Updated Systematic Review and Meta-analysis.
AB  - The aim of this study was to update the evidence on the surgical management of
      endometriosis-associated pain. Does laparoscopic excision offer any benefits over
      laparoscopic ablation? This is a systematic review and meta-analysis in which we
      searched MEDLINE, Embase, Institute for Scientific Information conference
      proceedings, the International Standard Randomised Controlled Trial Number
      registry, the Register and Meta-register for randomized controlled trials, the
      World Health Organization trials search portal, the Cochrane Library, and the
      British Library of electronic theses. Three randomized controlled trials were
      included, which enrolled 335 participants with a sample size per study ranging
      from 24 to 178 participants. Of these 3 studies, data from 2 could be pooled for
      meta-analysis. The primary outcome measure was the reduction in the visual analog
      scale score for dysmenorrhea. The secondary outcome measures included the
      reduction in the visual analog scale score for dyspareunia, dyschezia, and
      chronic pelvic pain and the reduction in Endometriosis Health Profile-30 core
      pain scores. The meta-analysis showed that the excision group had a significantly
      greater reduction in symptoms of dysmenorrhea (mean difference [MD] = 0.99; 95%
      confidence interval [CI], -0.02 to 2.00; p = .05) and dyschezia (MD = 1.31; 95%
      CI, 0.33-2.29; p = .009) compared with ablation. The symptoms of dyspareunia
      showed a nonsignificant benefit with excision (MD = 0.96; 95% CI, -0.07 to 1.99;
      p = .07). Data from 1 study showed a significant reduction in chronic pelvic pain
      (MD = 2.57; 95% CI, 1.27-3.87; p = .0001) and Endometriosis Health Profile-30
      core pain scores (MD = 13.20; 95% CI, 3.70-22.70; p = .006) with the excision
      group compared with the ablation group. The limited available evidence shows that
      at 12 months postsurgery, symptoms of dysmenorrhea, dyschezia, and chronic pelvic
      pain secondary to endometriosis showed a significantly greater improvement with
      laparoscopic excision compared with ablation.

PMID- 28456618
TI  - Protein tyrosine phosphatase conjugated with a novel transdermal delivery
      peptide, astrotactin 1-derived peptide recombinant protein tyrosine phosphatase
      (AP-rPTP), alleviates both atopic dermatitis-like and psoriasis-like dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) and psoriasis are the 2 most common chronic
      inflammatory skin diseases. There is an unmet medical need to overcome
      limitations for transcutaneous drug development posed by the skin barrier.
      OBJECTIVE: We aimed to identify a novel transdermal delivery peptide and to
      develop a transcutaneously applicable immunomodulatory protein for treating AD
      and psoriasis. METHODS: We identified and generated reporter proteins conjugated
      to astrotactin 1-derived peptide (AP), a novel transdermal delivery peptide of
      human origin, and analyzed the intracellular delivery efficiency of these
      proteins in mouse and human skin cells and tissues using multiphoton confocal
      microscopy. We also generated a recombinant therapeutic protein, AP-recombinant
      protein tyrosine phosphatase (rPTP), consisting of the phosphatase domain of the
      T-cell protein tyrosine phosphatase conjugated to AP. The immunomodulatory
      function of AP-rPTP was confirmed in splenocytes on cytokine stimulation and T
      cell receptor stimulation. Finally, we confirmed the in vivo efficacy of AP-rPTP
      transdermal delivery in patients with oxazolone-induced contact hypersensitivity,
      ovalbumin-induced AD-like, and imiquimod-induced psoriasis-like skin inflammation
      models. RESULTS: AP-conjugated reporter proteins exhibited significant
      intracellular transduction efficacy in keratinocytes, fibroblasts, and immune
      cells. In addition, transcutaneous administration of AP-dTomato resulted in
      significant localization into the dermis and epidermis in both mouse and human
      skin. AP-rPTP inhibited phosphorylated signal transducer and activator of
      transcription (STAT) 1, STAT3, and STAT6 in splenocytes and also regulated T-cell
      activation and proliferation. Transcutaneous administration of AP-rPTP through
      the paper-patch technique significantly ameliorated skin tissue thickening,
      inflammation, and cytokine expression in both AD-like and psoriasis-like
      dermatitis models. CONCLUSION: We identified a 9-amino-acid novel transdermal
      delivery peptide, AP, and demonstrated its feasibility for transcutaneous
      biologic drug development. Moreover, AP-rPTP is a novel immunomodulatory drug
      candidate for human dermatitis.

PMID- 28456619
TI  - Measuring long-term disease control in patients with atopic dermatitis: A
      validation study of well-controlled weeks.
AB  - BACKGROUND: Because atopic dermatitis (AD) is a relapsing remitting disease,
      assessing long-term control is important. Well-controlled weeks (WCWs) have been
      used to assess asthma long-term control but have never been validated for AD.
      OBJECTIVES: We sought to assess the feasibility, validity, and interpretability
      of WCWs in patients with AD. METHODS: Three studies of patients with moderate-to
      severe AD, including 4 to 6 months of daily/weekly symptom and treatment use
      data, were evaluated (study A, n = 336; study B, n = 60; and study C, n = 224).
      WCWs were defined by worsening symptoms and increased medication use.
      Feasibility, construct validity, and interpretability of WCWs were determined by
      assessing missing data, association with validated AD outcomes, and floor and
      ceiling effects. Analysis used linear and logistic regression. RESULTS: WCWs were
      feasible to collect: 95.2% (study A) and 94.7% (study B) contributed data for at
      least half of the weekly data points, and 93.2% and 88.7% contributed to all data
      points up to 4 months. WCWs were significantly associated with validated AD
      severity instruments, including patient-orientated outcome measures and objective
      signs (Eczema Area and Severity Index, Three Item Severity Score, and Six Signs,
      Six Areas Atopic Dermatitis Scale). The odds of experiencing a WCW if AD severity
      was clear/mild was 5.8 (95% CI, 3.5-9.7), 1.9 (95% CI, 0.8-4.4), and 8.1 (95% CI,
      4.5-14.6) in studies A, B, and C, respectively. WCWs were associated with ceiling
      effects: 31.6% (study A) and 37.5% (study B) of participants had no WCWs more
      than 90% of the time. CONCLUSIONS: WCWs are valid and feasible for measuring long
      term control in AD trials. However, ceiling effects and burden of data collection
      can limit use.

PMID- 28456620
TI  - Serum IgG and risk of exacerbations and hospitalizations in chronic obstructive
      pulmonary disease.

PMID- 28456621
TI  - IgE sensitization in relation to preschool eczema and filaggrin mutation.
AB  - BACKGROUND: Eczema (atopic dermatitis) is associated with an increased risk of
      having IgE antibodies. IgE sensitization can occur through an impaired skin
      barrier. Filaggrin gene (FLG) mutation is associated with eczema and possibly
      also with IgE sensitization. OBJECTIVE: We sought to explore the longitudinal
      relation between preschool eczema (PSE), FLG mutation, or both and IgE
      sensitization in childhood. METHODS: A total of 3201 children from the BAMSE
      (Children Allergy Milieu Stockholm Epidemiology) birth cohort recruited from the
      general population were included. Regular parental questionnaires identified
      children with eczema. Blood samples were collected at 4, 8, and 16 years of age
      for analysis of specific IgE. FLG mutation analysis was performed on 1890 of the
      children. RESULTS: PSE was associated with IgE sensitization to both food
      allergens and aeroallergens up to age 16 years (overall adjusted odds ratio,
      2.30; 95% CI, 2.00-2.66). This association was even stronger among children with
      persistent PSE. FLG mutation was associated with IgE sensitization to peanut at
      age 4 years (adjusted odds ratio, 1.88; 95% CI, 1.03-3.44) but not to other
      allergens up to age 16 years. FLG mutation and PSE were not effect modifiers for
      the association between IgE sensitization and PSE or FLG mutation, respectively.
      Sensitized children with PSE were characterized by means of polysensitization,
      but no other specific IgE sensitization patterns were found. CONCLUSIONS: PSE is
      associated with IgE sensitization to both food allergens and aeroallergens up to
      16 years of age. FLG mutation is associated with IgE sensitization to peanut but
      not to other allergens. Sensitized children with preceding PSE are more often
      polysensitized.

PMID- 28456622
TI  - Bruton tyrosine kinase inhibition: Clinical relevance beyond B cells.

PMID- 28456623
TI  - Oral corticosteroid exposure and adverse effects in asthmatic patients.
AB  - BACKGROUND: Significant adverse effects (AEs) have been associated with
      continuous exposure to oral corticosteroids (OCSs). The potential association
      with intermittent exposure is unknown. OBJECTIVE: We sought to assess the
      association between OCSs and AEs based on the number of OCS prescriptions.
      METHODS: This was a retrospective cohort study of asthmatic patients 18 years and
      older in the 2000-2014 MarketScan data set. Propensity score matching was used at
      baseline (12 months before the index date: first OCS use). Logistic regression
      was used to examine the association between OCSs and new incident AEs (either
      combined or individual) controlling for covariates. Follow-up continued for 24
      months minimum and 10 years maximum after the index date. RESULTS: There were
      72,063 and 156,373 subjects in the OCS and no OCS cohorts, respectively. Subjects
      taking 4 or more OCS (1-3) prescriptions within the year had 1.29 (1.04) times
      the odds of experiencing a new AE within the year. Each year of exposure to 4 or
      more OCS prescriptions (current and past) resulted in 1.20 times the odds of
      having an AE in the current year. Exposure to 4 or more prescriptions was
      associated with significantly greater odds of AEs for osteoporosis, hypertension,
      obesity, type 2 diabetes, gastrointestinal ulcers/bleeds, fractures, and
      cataracts (odds, 1.21-1.44 depending on the AE). CONCLUSION: Although previous
      research has documented the deleterious effect of continuous OCS exposure in
      patients with severe asthma, our results suggest that each OCS prescription might
      result in a cumulative burden on current and future health regardless of dose and
      duration. OCS-sparing strategies are extremely important to improve patient
      outcomes.

PMID- 28456624
TI  - Fusion proteins of flagellin and the major birch pollen allergen Bet v 1 show
      enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity.
AB  - BACKGROUND: Recombinant fusion proteins of flagellin and antigens have been
      demonstrated to induce strong innate and adaptive immune responses. Such fusion
      proteins can enhance the efficacy of allergen-specific immunotherapy. OBJECTIVE:
      We sought to characterize different fusion proteins of flagellin and the major
      birch pollen allergen Bet v 1 for suitability as allergy vaccines. METHODS: A
      truncated version of flagellin (NtCFlg) was genetically fused to the N- or C
      terminus of Bet v 1. Toll-like receptor (TLR) 5 binding was assessed with HEK293
      cells expressing TLR5. Upregulation of CD40, CD80, CD83, and CD86 on monocyte
      derived dendritic cells from allergic patients was analyzed by using flow
      cytometry. The T cell-stimulatory capacity of the fusion proteins was assessed
      with naive and Bet v 1-specific T cells. IgE binding was tested in inhibition
      ELISAs and basophil activation tests. Mice were immunized with the fusion
      proteins in the absence and presence of aluminum hydroxide. Cellular and antibody
      responses were monitored. Murine antibodies were tested for blocking capacity in
      basophil activation tests. RESULTS: Both fusion proteins matured monocyte-derived
      dendritic cells through TLR5. Compared with Bet v 1, the fusion proteins showed
      stronger T cell-stimulatory and reduced IgE-binding capacity and induced murine
      Bet v 1-specific antibodies in the absence of aluminum hydroxide. However, only
      antibodies induced by means of immunization with NtCFlg fused to the C-terminus
      of Bet v 1 inhibited binding of patients' IgE antibodies to Bet v 1. CONCLUSION:
      Bet v 1-flagellin fusion proteins show enhanced immunogenicity, reduced
      allergenicity, and intrinsic adjuvanticity and thus represent promising vaccines
      for birch pollen allergen-specific immunotherapy. However, the sequential order
      of allergen and adjuvant within a fusion protein determines its immunologic
      characteristics.

PMID- 28456625
TI  - Effects of matsutake mushroom scent compounds on tyrosinase and murine B16-F10
      melanoma cells.
AB  - Tyrosinase-catalyzed l-tyrosine oxidation is a key step in melanogenesis, and
      intense melanin formation is often a problem in chemotherapies or food
      preservation. Here we report that methyl cinnamate one of the constituents
      characterized from mycelium and sporocarp of American matsutake mushroom
      Tricholoma magnivelare inhibits both enzymatic and cellular melanin formation.
      Methyl cinnamate inhibits mushroom tyrosinase-catalyzed l-tyrosine oxidation
      while the oxidation of l-3,4-dihydroxyphenylalanine (l-DOPA) was not inhibited.
      In subsequent cellular assays, methyl cinnamate significantly suppressed
      melanogenesis of murine B16-F10 melanoma cells without affecting cell growth.
      However, methyl 3-phenylpropionate, a dihydro-derivative of methyl cinnamate, did
      not possess melanogenesis, indicating that the double bond in the enone moiety is
      a key Michael reaction acceptor to elicit the activity. In addition, a rather
      rare chlorinated benzaldehyde derivative, 3,5-dichloro-4-methoxybenzaldehyde
      isolated from the same source, was found to show potent cytotoxicity, and the
      chlorine atom reduced a tyrosinase inhibitory activity but enhanced cytotoxicity.
      Our findings suggest that methyl cinnamate is a novel melanogenesis inhibitor
      from natural sources.

PMID- 28456626
TI  - Compound 21 and Telmisartan combination mitigates type 2 diabetic nephropathy
      through amelioration of caspase mediated apoptosis.
AB  - The current study aimed to understand the role of novel, highly selective, orally
      active, non-peptide Angiotensin II type 2 receptor (AT2R) agonist, Compound 21
      and its potential additive effect with Telmisartan on apoptosis and underlying
      posttranslational modifications in a non-genetic murine model for type 2 diabetic
      nephropathy (T2DN). An experimental model for T2DN was developed by administering
      low dose Streptozotocin in high fat diet fed male Wistar rats, followed by their
      treatment with Telmisartan, C21 or their combination. Our results demonstrated
      that C21 and Telmisartan combination attenuated metabolic and renal dysfunction,
      renal morphological and micro-architectural aberrations and hemodynamic
      disturbances in type 2 diabetic rats. The anti-apoptotic and anti-inflammatory
      effects of Telmisartan were significantly accentuated by C21 indicated by
      expression of apoptotic markers (Parp1, Caspase 8, Caspase 7, cleaved PARP and
      cleaved Caspase 3) and NF-kappaB mediated inflammatory molecules like interleukin
      6, tumour necrosis factor alpha; monocyte chemoattractant protein 1 and vascular
      cell adhesion molecule 1. C21 was found to improve Telmisartan mediated reversal
      of histone H3 acetylation at lysine 14 and 27 and expression of histone acetyl
      transferase, p300/CBP-associated factor also known to regulate NF-kappaB activity
      and DNA damage response. C21 in combination with Telmisartan markedly mitigates
      caspase mediated apoptosis and NF-kappaB signalling in T2D kidney, which could be
      partially attributed to its influence on PCAF mediated histone H3 acetylation.
      Hence further research should be done to develop this combination to treat T2DN.

PMID- 28456627
TI  - Constitutive omega-3 fatty acid production in fat-1 transgenic mice and
      docosahexaenoic acid administration to wild type mice protect against 2,4,6
      trinitrobenzene sulfonic acid-induced colitis.
AB  - Omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) are known to have strong
      anti-inflammatory effects. In the present study, we investigated the protective
      effects of omega-3 PUFAs on experimentally induced murine colitis. Intrarectal
      administration of 2.5% 2,4,6-trinitrobenzene sulfonic acid (TNBS) caused
      inflammation in the colon of wild type mice, but this was less severe in fat-1
      transgenic mice that constitutively produce omega-3 PUFAs from omega-6 PUFAs. The
      intraperitoneal administration of docosahexaenoic acid (DHA), a representative
      omega-3 PUFA, was also protective against TNBS-induced murine colitis. In
      addition, endogenously formed and exogenously introduced omega-3 PUFAs attenuated
      the production of malondialdehyde and 4-hydroxynonenal in the colon of TNBS
      treated mice. The effective protection against inflammatory and oxidative colonic
      tissue damages in fat-1 and DHA-treated mice was associated with suppression of
      NF-kappaB activation and cyclooxygenase-2 expression and with elevated activation
      of Nrf2 and upregulation of its target gene, heme oxygenase-1. Taken together,
      these results provide mechanistic basis of protective action of omega-3 fatty
      PUFAs against experimental colitis.

PMID- 28456628
TI  - Structural pharmacological studies on EGFR T790M/C797S.
AB  - Drug-resistance is a major challenge in targeted therapy of EGFR mutated non
      small cell lung cancers (NSCLCs). The third-generation irreversible inhibitors
      such as AZD9291, CO-1686 and WZ4002 can overcome EGFR T790M drug-resistance
      mutant through covalent binding through Cys 797, but ultimately lose their
      efficacy upon emergence of the new mutation C797S. To develop new reversible
      inhibitors not relying on covalent binding through Cys 797 is therefore urgently
      demanded. Go6976 is a staurosporine-like reversible inhibitor targeting T790M
      while sparing the wild-type EGFR. In the present work, we reported the complex
      crystal structures of EGFR T790M/C797S + Go6976 and T790M + Go6976, along with
      enzyme kinetic data of EGFR wild-type, T790M and T790M/C797S. These data showed
      that the C797S mutation does not significantly alter the structure and function
      of the EGFR kinase, but increases the local hydrophilicity around residue 797.
      The complex crystal structures also elucidated the detailed binding mode of
      Go6976 to EGFR and explained why this compound prefers binding to T790M mutant.
      These structural pharmacological data would facilitate future drug development
      studies.

PMID- 28456630
TI  - Th17 cell-mediated immune responses promote mast cell proliferation by triggering
      stem cell factor in keratinocytes.
AB  - Although mast cells are traditionally thought to function as effector cells in
      allergic responses, they have increasingly been recognized as important
      regulators of various immune responses. Mast cells mature locally; thus, tissue
      specific influences are important for promoting mast cell accumulation and
      survival in the skin and the gastrointestinal tract. In this study, we determined
      the effects of keratinocytes on mast cell accumulation during Th17-mediated skin
      inflammation. We observed increases in dermal mast cells in imiquimod-induced
      psoriatic dermatitis in mice accompanied by the expression of epidermal stem cell
      factor (SCF), a critical mast cell growth factor. Similar to mouse epidermal
      keratinocytes, SCF was highly expressed in the human HaCaT keratinocyte cell line
      following stimulation with IL-17. Further, keratinocytes promoted mast cell
      proliferation following stimulation with IL-17 in vitro. However, the effects of
      keratinocytes on mast cells were significantly diminished in the presence of anti
      CD117 (stem cell factor receptor) blocking antibodies. Taken together, our
      results revealed that the Th17-mediated inflammatory environment promotes mast
      cell accumulation through keratinocyte-derived SCF.

PMID- 28456629
TI  - Mitochondrial adventures at the organelle society.
AB  - Mitochondria are constantly communicating with the rest of the cell. Defects in
      mitochondria underlie severe pathologies, whose mechanisms remain poorly
      understood. It is becoming increasingly evident that mitochondrial malfunction
      resonates in other organelles, perturbing their function and their biogenesis. In
      this manuscript, we review the current knowledge on the cross-talk between
      mitochondria and other organelles, particularly lysosomes, peroxisomes and the
      endoplasmic reticulum. Several organelle interactions are mediated by
      transcriptional programs, and other signaling mechanisms are likely mediating
      organelle dysfunction downstream of mitochondrial impairments. Many of these
      organelle crosstalk pathways are likely to have a role in pathological processes.

PMID- 28456631
TI  - Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND & AIMS: The epidemiology of Helicobacter pylori infection has changed
      with improvements in sanitation and methods of eradication. We performed a
      systematic review and meta-analysis to evaluate changes in the global prevalence
      of H pylori infection. METHODS: We performed a systematic search of the MEDLINE
      and EMBASE databases for studies of the prevalence of H pylori infection
      published from January 1, 1970 through January 1, 2016. We analyzed data based on
      United Nations geoscheme regions and individual countries. We used a random
      effects model to calculate pooled prevalence estimates with 95% confidence
      intervals (CIs), weighted by study size. We extrapolated 2015 prevalence
      estimates to obtain the estimated number of individuals with H pylori infection.
      RESULTS: Among 14,006 reports screened, we identified 263 full-text articles on
      the prevalence of H pylori infection; 184 were included in the final analysis,
      comprising data from 62 countries. Africa had the highest pooled prevalence of H
      pylori infection (70.1%; 95% CI, 62.6-77.7), whereas Oceania had the lowest
      prevalence (24.4%; 95% CI, 18.5-30.4). Among individual countries, the prevalence
      of H pylori infection varied from as low as 18.9% in Switzerland (95% CI, 13.1
      24.7) to 87.7% in Nigeria (95% CI, 83.1-92.2). Based on regional prevalence
      estimates, there were approximately 4.4 billion individuals with H pylori
      infection worldwide in 2015. CONCLUSIONS: In a systematic review and meta
      analysis to assess the prevalence of H pylori infection worldwide, we observed
      large amounts of variation among regions-more than half the world's population is
      infected. These data can be used in development of customized strategies for the
      global eradication.

PMID- 28456633
TI  - Optineurin in amyotrophic lateral sclerosis: Multifunctional adaptor protein at
      the crossroads of different neuroprotective mechanisms.
AB  - When optineurin mutations showed up on the amyotrophic lateral sclerosis (ALS)
      landscape in 2010, they differed from most other ALS-causing genes. They seemed
      to act by loss- rather than gain-of-function, and it was unclear how a
      polyubiquitin-binding adaptor protein, which was proposed to regulate a variety
      of cellular functions including cell signaling and vesicle trafficking, could
      mediate neuroprotection. This review discusses the considerable progress that has
      been made since then. A large number of mutations in optineurin and optineurin
      interacting proteins TANK-binding kinase (TBK1) and p62/SQSTM-1 have been found
      in the ALS patients, suggesting a common neuroprotective pathway. Moreover,
      functional studies of the ALS-causing optineurin mutations and the recently
      established optineurin ubiquitin-binding deficient and knockout mouse models
      helped identify three major mechanisms likely to mediate neuroprotection:
      regulation of autophagy, mitigation of (chronic) inflammatory signaling, and
      blockade of necroptosis. These three processes crosstalk, and require multiple
      levels of control, many of which can be mediated by optineurin. Based on the role
      of optineurin in multiple processes and the unexpected finding that targeted
      optineurin deletion in microglia and oligodendrocytes ultimately leads to the
      same phenotype of axonal degeneration despite different initial defects, we
      propose that the failure of the weakest link in the optineurin neuroprotective
      network is sufficient to disturb homeostasis and set-off the domino effect that
      could ultimately lead to neurodegeneration.

PMID- 28456632
TI  - Tumor Necrosis Factor Inhibits Spread of Hepatitis C Virus Among Liver Cells,
      Independent From Interferons.
AB  - BACKGROUND & AIMS: Tumor necrosis factor (TNF) is an inflammatory cytokine
      expressed by human fetal liver cells (HFLCs) after infection with cell culture
      derived hepatitis C virus (HCV). TNF has been reported to increase entry of HCV
      pseudoparticles into hepatoma cells and inhibit signaling by interferon alpha
      (IFNalpha), but have no effect on HCV-RNA replication. We investigated the
      effects of TNF on HCV infection of and spread among Huh-7 hepatoma cells and
      primary HFLCs. METHODS: Human hepatoma (Huh-7 and Huh-7.5) and primary HFLCs were
      incubated with TNF and/or recombinant IFNA2A, IFNB, IFNL1, and IFNL2 before or
      during HCV infection. We used 2 fully infectious HCV chimeric viruses of genotype
      2A in these studies: J6/JFH (clone 2) and Jc1(p7-nsGluc2A) (Jc1G), which encodes
      a secreted luciferase reporter. We measured HCV replication, entry, spread,
      production, and release in hepatoma cells and HFLCs. RESULTS: TNF inhibited
      completion of the HCV infectious cycle in hepatoma cells and HFLCs in a dose
      dependent and time-dependent manner. This inhibition required TNF binding to its
      receptor. Inhibition was independent of IFNalpha, IFNbeta, IFNL1, IFNL2, or Janus
      kinase signaling via signal transducer and activator of transcription. TNF
      reduced production of infectious viral particles by Huh-7 and HFLC, and thereby
      reduced the number of infected cells and focus size. TNF had little effect on HCV
      replicons and increased entry of HCV pseudoparticles. When cells were incubated
      with TNF before infection, the subsequent antiviral effects of IFNs were
      increased. CONCLUSIONS: In a cell culture system, we found TNF to have antiviral
      effects independently of, as well as in combination with, IFNs. TNF inhibits HCV
      infection despite increased HCV envelope glycoprotein-mediated infection of liver
      cells. These findings contradict those from other studies, which have reported
      that TNF blocks signal transduction in response to IFNs. The destructive
      inflammatory effects of TNF must be considered along with its antiviral effects.

PMID- 28456634
TI  - Does Surgeon Experience Affect Operative Time, Adverse Events and Continence
      Outcomes in Holmium Laser Enucleation of the Prostate? A Review of More Than
      1,000 Cases.
AB  - PURPOSE: Holmium laser enucleation of the prostate has become an increasingly
      common surgical therapy for benign prostatic hyperplasia. However, the
      relationship between surgeon experience and surgical outcomes has not yet been
      fully investigated. In this study we investigated how surgeon experience with
      holmium laser enucleation of the prostate affected operative time, adverse events
      and outcomes related to urination. MATERIALS AND METHODS: We gathered a total of
      1,113 cases of holmium laser enucleation of the prostate from 5 hospitals in
      Hyogo Prefecture, Japan. Included were data on surgeon experience with the
      procedure, operative time, enucleation time, morcellation time, patient age,
      perioperative and postoperative surgery related complications, and outcomes
      related to urination. RESULTS: A total of 39 surgeons were included in analysis.
      Statistical data showed that increasing surgical experience significantly
      contributed only to surgical time, enucleation time and urinary incontinence
      after holmium laser enucleation (p = 0.0146, 0.0216 and 0.0405, respectively). No
      significant changes were seen postoperatively in surgery related factors such as
      morcellation time, resected prostate volume, infectious or noninfectious surgery
      related complications, or urination related outcomes (p >0.05) Experience with at
      least 20 cases in particular affected surgical time (p = 0.0050), enucleation
      time (p = 0.0068) and urinary incontinence after holmium laser enucleation (p =
      0.0021). CONCLUSIONS: Surgeon experience contributed to shortened operative time
      and enucleation time, and to decreased postoperative urinary incontinence but not
      to surgery related complications or urination related outcomes as shown by
      maximum urine flow and post-void residual urine volume. We also found that
      experienced surgeons with 31 to 50 cases might be associated with complications
      after holmium laser enucleation in larger prostate cases. Based on these data
      further prospective studies are scheduled to establish a program for training in
      holmium laser enucleation of the prostate.

PMID- 28456636
TI  - Continuous-flow injection microfluidic thrombin assays: The effect of binding
      kinetics on observed enzyme inhibition.
AB  - A microfluidic assay for monitoring the inhibition of thrombin peptidase activity
      was developed. The system, which utilised soluble reagents in continuous-flow
      injection mode, was configured so as to allow inhibitor titrations via gradient
      formation. This microfluidic continuous-flow injection titration assay (CFITA)
      enabled the potency of a set of small-molecule serine peptidase inhibitors (SPIs)
      to be evaluated. The results, compared to standard microtiter plate (MTP) data,
      indicated that a microfluidic CFITA provided an efficient and effective method
      for evaluating compound potency. Crucially, whereas for fast-acting compounds the
      rank order of potency between the CFITA and MTP methods was preserved, for slow
      acting compounds the observed CFITA potencies were significantly lower. These
      results, in conjunction with data from computer simulations, clearly demonstrated
      that continuous-flow assays, and perhaps microfluidic assays in general, must
      take into account binding kinetics when used to assess reaction criteria.

PMID- 28456635
TI  - Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO
      Guideline.
AB  - PURPOSE: This multidisciplinary, evidence-based guideline for clinically non
      metastatic muscle-invasive bladder cancer focuses on the evaluation, treatment
      and surveillance of muscle-invasive bladder cancer guided toward curative intent.
      MATERIALS AND METHODS: A systematic review utilizing research from the Agency for
      Healthcare Research and Quality as well as additional supplementation by the
      authors and consultant methodologists was used to develop the guideline. Evidence
      based statements were based on body of evidence strengths Grade A, B or C and
      were designated as Strong, Moderate and Conditional Recommendations with
      additional statements presented in the form of Clinical Principles or Expert
      Opinions. RESULTS: For the first time for any type of malignancy, the American
      Urological Association, American Society of Clinical Oncology, American Society
      for Radiation Oncology and Society of Urologic Oncology have formulated an
      evidence-based guideline based on a risk-stratified clinical framework for the
      management of muscle-invasive urothelial bladder cancer. This document is
      designed to be used in conjunction with the associated treatment algorithm.
      CONCLUSIONS: The intensity and scope of care for muscle-invasive bladder cancer
      should focus on the patient, disease and treatment response characteristics. This
      guideline attempts to improve a clinician's ability to evaluate and treat each
      patient, but higher quality evidence in future trials will be essential to
      improve level of care for these patients.

PMID- 28456637
TI  - A fast method for high resolution oxymetry study of skeletal muscle mitochondrial
      respiratory chain complexes.
AB  - High resolution oxymetry study (HROS) of skeletal muscle usually requires 90-120
      min preparative phase (dissection, permeabilization and washing). This work
      reports on the suitability of a rapid muscle preparation which by-passes this
      long preparation. For a few seconds only, muscle biopsy from pigs is submitted to
      gentle homogenization at 8000 rotations per minute using an ultra-dispersor
      apparatus. Subsequent HROS is performed using FCCP instead of ADP, compounds
      crossing and not plasma membrane, respectively. This simplified procedure
      compares favorably with classical (permeabilized fibers) HROS in terms of
      respiratory chain complex activities. Mitochondria from cells undergoing
      ultradispersion were functionally preserved as attested by relative inefficacy of
      added cytochrome C (not crossing intact mitochondrial outer membrane) to
      stimulate mitochondrial respiration. Responsiveness of respiration to ADP (in the
      absence of FCCP) suggested that these intact mitochondria were outside cells
      disrupted by ultradispersion or within cells permeated by this procedure.

PMID- 28456638
TI  - [Polycystic kidney disease: An analysis of e-patients exchanges in the public
      blogosphere].
AB  - The goal this study was to understand the preoccupations of e-patients with
      Autosomal Dominant Polycystic Kidney Disease (ADPKD), through their discussions
      on social networks, and to compare them with those of members of a specialized
      association. We collected and analyzed all messages containing an unequivocal
      expression of the pathology (polycystic kidney disease, PKD, ADPKD, etc.)
      available on public forums on the French Internet and all french-language
      messages posted on the forum of the patient group Association Polykystose-France
      (PKD-France) during 2 years. The automated processing of messages (extraction of
      themes), using a referential associating each theme with a variety of
      expressions, allowed classification in different thematic families. 8494themes
      were extracted from 764 messages sent by 329 different users on 68 public forum
      websites. The main thematic families were treatments (17%), pathology (16%),
      signs and symptoms (13%), feelings (11%), healthcare system (7%) and patient life
      (7%). On the association's forum, 345 messages were sent by 57 different members.
      The thematic richness was equivalent (number of themes per message: 10.2 versus
      11.1 respectively), with 3517 themes, but the thematic families corresponded more
      to the emotional aspects and daily problems: Feelings (15.5%) came before
      treatment (14.5%), then anatomy (9%) before the healthcare system (8%) and
      pathology (7%). Knowing the e-patients' views expressed on the internet will
      enable physicians to respond to patients real expectations and correct erroneous
      perceptions. As for the patients, they will know the leading sites of opinion,
      shared by their peers.

PMID- 28456639
TI  - [Hypercalcemia and inactive mutation of CYP24A1. Case-study and literature
      review].
AB  - We present the case of a family whose members have high levels of serum calcium
      (hypercalcaemia) by loss of function of the enzyme vitamin D 24-hydroxylase due
      to bi-allelic mutations in the CYP24A1 gene: c.443 T>C (p.Leu148Pro) and c.1187
      G>A (p.Arg396Gln). 24-VITD hydroxylase is a key player in regulating the
      circulating calcitriol, its tissue concentration and its biological effects.
      Transmission is recessive. The estimated prevalence of stones in the affected
      subjects is estimated between 10 and 15%. The loss of peripheral catabolism of
      vitamin D metabolites in patients with an inactivating mutation of CYP24A1 is
      responsible for persistent high levels of 1,25-dihydroxyvitamin D especially
      after sun exposure and a charge of native vitamin D. Although there are currently
      no recommendations (French review) on this subject, this disease should be
      suspected in association with recurrent calcium stones with nephrocalcinosis, and
      a calcitriol-dependent hypercalcaemia with adapted low parathyroid hormone
      levels. Resistance to corticosteroid therapy distinguishes it from other
      calcitriol-dependent hypercalcemia. A ratio of 25-hydroxyvitamin D/24.25
      hydroxyvitamin D>50, is in favor of hypercalcemia with vitamin D deficiency 24
      hydroxylase. Genetic analysis of CYP24A1 should be performed at the second step.
      The current therapeutic management includes the restriction native vitamin D
      supplementation and the limitation of sun exposure. Biological monitoring will be
      based on serum calcium control and modulation of parathyroid hormone
      concentrations.

PMID- 28456640
TI  - Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.
AB  - BACKGROUND: This study was designed to identify novel links between lipid species
      and disease progression in non-alcoholic fatty liver disease (NAFLD). METHODS: We
      analyzed lipid species in the liver and plasma of db/db mice fed a choline
      deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid
      chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed
      using HepG2 cells stimulated with recombinant human TNFalpha or IL1beta. The
      expression of steatosis-, inflammation-, and fibrosis-related genes were
      analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS.
      RESULTS: The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild
      fibrosis, obesity, and hypercholesterolemia displayed significantly higher
      hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated
      adrenic acid in the CDAHFD-fed db/db mice was associated with increased
      expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene
      during peroxisomal beta-oxidation. The pretreatment of HepG2 cells with adrenic
      acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In
      NAFLD patients, the group with the highest ALT levels exhibited higher plasma
      adrenic acid concentrations than the other ALT groups (p-value for trend <0.001).
      CONCLUSION: Data obtained demonstrated that adrenic acid accumulation contributes
      to disease progression in NAFLD.

PMID- 28456641
TI  - Low-density lipoprotein oxidation biomarkers in human health and disease and
      effects of bioactive compounds.
AB  - Based on the significance of oxidized low-density lipoprotein (LDL) in health and
      disease, this review focuses on human studies addressing oxidation of LDL,
      including three lines of biomarkers, (i) ex vivo LDL resistance to oxidation, a
      "challenge test" model, (ii) circulating oxidized LDL, indicating the "current in
      vivo status", and (iii) autoantibodies against oxidized LDL as fingerprints of an
      immune response to oxidized LDL, along with circulating oxysterols and 4
      hydroxynonenal as biomarkers of lipid peroxidation. Lipid peroxidation and
      oxidized LDL are hallmarks in the development of various metabolic,
      cardiovascular and other diseases. Changes further occur across life stages from
      infancy to older age as well as in athletes and smokers. Given their
      responsiveness to targeted nutritional interventions, markers of LDL oxidation
      have been employed in a rapidly growing number of human studies for more than 2
      decades. There is growing interest in foods, which, besides providing energy and
      nutrients, exert beneficial effects on human health, such as protection of DNA,
      proteins and lipids from oxidative damage. Any health claim, however, needs to be
      substantiated by supportive evidence derived from human studies, using reliable
      biomarkers to demonstrate such beneficial effects. A large body of evidence has
      accumulated, demonstrating protection of LDL from oxidation by bioactive food
      compounds, including vitamins, other micronutrients and secondary plant
      ingredients, which will facilitate the selection of oxidation biomarkers for
      future human intervention studies and health claim support.

PMID- 28456642
TI  - Pathophysiology of mitochondrial lipid oxidation: Role of 4-hydroxynonenal (4
      HNE) and other bioactive lipids in mitochondria.
AB  - Mitochondrial lipids are essential for maintaining the integrity of mitochondrial
      membranes and the proper functions of mitochondria. As the "powerhouse" of a
      cell, mitochondria are also the major cellular source of reactive oxygen species
      (ROS). Oxidative stress occurs when the antioxidant system is overwhelmed by
      overproduction of ROS. Polyunsaturated fatty acids in mitochondrial membranes are
      primary targets for ROS attack, which may lead to lipid peroxidation (LPO) and
      generation of reactive lipids, such as 4-hydroxynonenal. When mitochondrial
      lipids are oxidized, the integrity and function of mitochondria may be
      compromised and this may eventually lead to mitochondrial dysfunction, which has
      been associated with many human diseases including cancer, cardiovascular
      diseases, diabetes, and neurodegenerative diseases. How mitochondrial lipids are
      oxidized and the underlying molecular mechanisms and pathophysiological
      consequences associated with mitochondrial LPO remain poorly defined. Oxidation
      of the mitochondria-specific phospholipid cardiolipin and generation of bioactive
      lipids through mitochondrial LPO has been increasingly recognized as an important
      event orchestrating apoptosis, metabolic reprogramming of energy production,
      mitophagy, and immune responses. In this review, we focus on the current
      understanding of how mitochondrial LPO and generation of bioactive lipid
      mediators in mitochondria are involved in the modulation of mitochondrial
      functions in the context of relevant human diseases associated with oxidative
      stress.

PMID- 28456644
TI  - Chitosan - Locust bean gum interpenetrating polymeric network nanocomposites for
      delivery of aceclofenac.
AB  - In this study, aceclofenac-loaded IPN nanocomposites were developed based on
      natural polysaccharides namely chitosan (CS) and locust bean gum (LBG) using
      glutaraldehyde as cross-linker. Infrared spectroscopy analysis confirmed the
      formation of composite materials and ensured the chemical compatibility between
      drug and polymers. The effect of component polymers on the drug entrapment
      efficiency (DEE) and particle size of the composites was examined. Increasing LBG
      content actually decreased the DEE from 72% to 40% and produced larger particles
      of 372-485nm dimensions. However, an opposite trend was noted as the
      concentration of CS was increased. Out of these composites, the maximum drug
      entrapment efficiency of 78.92% and smallest composites of 318nm-size was
      obtained at LBG: CS mass ratio of 1:5. However, CS: LBG (1:5) provided the
      slowest drug release profiles in phosphate buffer solution (pH 6.8) up to 8h. The
      drug release data corroborated well with the swelling properties of the
      nanocomposites. The composite systems efficiently suppressed the burst release of
      drug in acidic medium (pH 1.2). The drug delivery from the nanocomposites
      occurred via anomalous transport mechanism in vitro. Overall, this novel chitosan
      and LBG-based nanocomposites system could minimize the gastrointestinal side
      effects of the drug by providing medication in a slow sustained fashion.

PMID- 28456645
TI  - Preparation of amino-functionalized regenerated cellulose membranes with high
      catalytic activity.
AB  - The modification of regenerated cellulose (RC) membranes was carried out by using
      silane coupling agents presenting primary and secondary amino-groups. The
      grafting of the amino groups onto the modified cellulose molecule was confirmed
      by X-ray photoelectron spectroscopies and 13C nuclear magnetic resonance
      spectroscopic analyses. The crystallinity of the cellulose membranes (CM)
      decreased after chemical modification as indicated by the X-ray diffraction
      results. Moreover, a denser structure was observed at the surface and cross
      section of the modified membranes by SEM images. The contact angle measurements
      showed that the silane coupling treatment enhanced the hydrophobicity of the
      obtained materials. Then the catalytic properties of two types of modified
      membranes were studied in a batch process by evaluating their catalytic
      performance in a Knoevenagel condensation. The results indicated that the
      cellulose membrane grafted with many secondary amines exhibited a better
      catalytic activity compared to the one grafted only by primary amines. In
      addition, the compact structure of the modified membranes permitted their
      application in a pervaporation catalytic membrane reactor. Therefore, functional
      CM that prepared in this paper represented a promising material in the field of
      industrial catalysis.

PMID- 28456646
TI  - Monoolein-alginate beads as a platform to promote adenosine cutaneous
      localization and wound healing.
AB  - Alginate beads containing the polar lipid monoolein were developed as a strategy
      to manage wet wounds by providing improved uptake of excess exudate while
      releasing adenosine locally for promotion of healing. To obtain monoolein
      containing beads, the lipid was mixed with almond oil (2:1w/w), and emulsified
      within the alginate aqueous dispersion, followed by ionotropic gelation in CaCl2
      solution. Compared to alginate-only, monoolein-alginate systems were 1.44-fold
      larger, their swelling ability was 1.40-fold higher and adenosine cumulative
      release was approximately 1.30-fold lower (at 24h). Monoolein-alginate beads were
      considered safe for topical application as demonstrated by the absence of changes
      on the viability of reconstructed skin equivalents compared to PBS. Smaller
      amounts of adenosine were delivered by the beads into and across damaged porcine
      skin (created by an incisional wound) compared to the drug aqueous solution, and
      cutaneous localization was favored. More specifically, the beads increased the
      viable skin layer/receptor phase delivery ratio by approximately 4-fold at 12h
      post-application. Considering the wide range of adenosine physiological effects
      and the importance of skin localization for its use in wound healing, these
      results demonstrate the potential of monoolein-containing beads for localized
      drug delivery and management of wet wounds.

PMID- 28456647
TI  - Virus versus virus.

PMID- 28456648
TI  - Alkhurma hemorrhagic fever virus.
AB  - Alkhurma hemorrhagic fever virus (AHFV) was first isolated in Jeddah, Saudi
      Arabia, in the 1990s from the blood of a butcher. Subsequently, the virus was
      recognized in many patients in Saudi Arabia and rarely from Egypt and Djibouti.
      In this review, we summarize the current literature on AHFV globally with special
      focus on Saudi Arabia.

PMID- 28456643
TI  - Matrix metalloproteinase collagenolysis in health and disease.
AB  - The proteolytic processing of collagen (collagenolysis) is critical in
      development and homeostasis, but also contributes to numerous pathologies.
      Mammalian interstitial collagenolytic enzymes include members of the matrix
      metalloproteinase (MMP) family and cathepsin K. While MMPs have long been
      recognized for their ability to catalyze the hydrolysis of collagen, the roles of
      individual MMPs in physiological and pathological collagenolysis are less
      defined. The use of knockout and mutant animal models, which reflect human
      diseases, has revealed distinct collagenolytic roles for MT1-MMP and MMP-13. A
      better understanding of temporal and spatial collagen processing, along with the
      knowledge of the specific MMP involved, will ultimately lead to more effective
      treatments for cancer, arthritis, cardiovascular conditions, and infectious
      diseases. This article is part of a Special Issue entitled: Matrix
      Metalloproteinases edited by Rafael Fridman.

PMID- 28456650
TI  - Design of nonionic micelle-laden polysaccharide hydrogels for controlled delivery
      of hydrophobic drugs.
AB  - The incorporation of micelle self-assembly in hydrogels has been used to produce
      self-healing materials, materials with tunable mechanical properties, and
      hydrophilic or hydrophobic drug delivery systems. However, little is known about
      the connection among formulation - structure - properties (particularly
      transport) in these systems. This connection is explored in alkyl ethoxylate
      micelle-laden gellan gum hydrogels used as delivery system for the hydrophobic
      drug dexamethasone. Phase behavior maps and rheological characterization of the
      micelle-laden hydrogels indicate that their properties are largely dominated by
      the concentration and cloud point (CP) of the alkyl ethoxylate nonionic
      surfactant. The sol-gel temperature of the hybrid hydrogels was found to be close
      to the CP of the surfactant, and their storage modulus (G') was found to increase
      with increasing surfactant concentration. A detailed analysis of the phase
      behavior maps, and evaluations of the mesh size of the hybrid hydrogels suggest a
      novel mechanism whereby micelles associate with gellan gum strands during high
      temperature hydration, hindering the double-helix assembly of the strands upon
      cooling. This increases the number of single strands and the density of physical
      cross-links, reducing the mesh size of the hydrogel. This mesh size reduction led
      to a decrease in the effective diffusion coefficient of micelles in the gel, and
      extended the release time of dexamethasone from 2h in surfactant-free hydrogel to
      more than 2days in the micelle-laden hydrogel.

PMID- 28456649
TI  - The accessory Sec system (SecY2A2) in Streptococcus pneumoniae is involved in
      export of pneumolysin toxin, adhesion and biofilm formation.
AB  - In Streptococcus pneumoniae TIGR4, genes encoding a SecY2A2 accessory Sec system
      are present within a locus encoding a serine-rich repeat surface protein PsrP.
      Mutant strains deleted in secA2 or psrP were deficient in biofilm formation,
      while the DeltasecA2 mutant was reduced in binding to airway epithelial cells.
      Cell wall protein (CWP) fractions from the DeltasecA2 mutant, but not from the
      DeltapsrP mutant, were reduced in haemolytic (pneumolysin) activity. Contact
      dependent pneumolysin (Ply) activity of wild type TIGR4 cells was ten-fold
      greater than that of DeltasecA2 mutant cells suggesting that Ply was not active
      at the DeltasecA2 cell surface. Ply protein was found to be present in the CWP
      fraction from the DeltasecA2 mutant, but showed aberrant electrophoretic
      migration indicative of protein modification. Proteomic analyses led to the
      discovery that the DeltasecA2 mutant CWP fraction was deficient in two
      glycosidases as well as other enzymes involved in carbohydrate metabolism. Taken
      collectively the results suggest that positioning of Ply into the cell wall
      compartment in active form, together with glycosyl hydrolases and adhesins,
      requires a functional accessory Sec system.

PMID- 28456652
TI  - Sustained delivery of siRNA poly- and lipopolyplexes from porous macromer
      crosslinked gelatin gels.
AB  - RNA interference (RNAi) is a promising technique to treat severe diseases on a
      pre-protein level. We and others postulate that the release of nanoparticle
      complexed small interfering RNA (siRNA) from implanted biomaterials could provide
      structural support for tissue repair, combined with local siRNA transfection of
      invading and regenerating cells. In this study, we systematically investigated
      cross-linked gelatin based hydrogel formulations (cGEL) as degradable controlled
      release matrices for siRNA. Aiming at the definition of correlations between cGEL
      composition, siRNA nanoparticle formulation, release kinetics of complexed siRNA
      and transfection efficiency, we combined five different cGEL formulations and
      three transfection systems, i.e. polyplexes with polyethyleneimine (PEI), PEI in
      combination with liposomes (lipopolyplexes) and polyplexes based on tyrosin
      modified PEI (P10Y). It was found that the distribution of these poly
      /lipopolyplexes, when applied onto the negatively charged hydrogels, was strongly
      dependent on their zeta potential. Furthermore, siRNA release from the hydrogel
      was a multifactorial process, as diffusion, hydrogel degradation and nanoparticle
      decomplexation overlapped over time. This resulted in a prolonged release of
      siRNA for up to 21days. In the case of PEI complexes and lipopolyplexes, release
      kinetics depended on the cGEL formulation. In contrast, when employing P10Y
      polyplexes, an initial burst release was observed with no further release
      thereafter. Silencing activity was determined using constitutively luciferase
      expressing SKOV-3-Luc reporter cells. Surface and bulk porosity in hydrogels was
      introduced by addition of soluble polyethylene glycol during fabrication, leading
      to improved knockdown. The rapid onset of knockdown efficacy will also provide
      the basis for the determination of long-term effects.

PMID- 28456651
TI  - Development and evaluation of injectable nanosized drug delivery systems for
      apigenin.
AB  - The purpose of this study was to develop different injectable nanosized drug
      delivery systems (NDDSs) i.e. liposome, lipid nanocapsule (LNC) and polymeric
      nanocapsule (PNC) encapsulating apigenin (AG) and compare their characteristics
      to identify the nanovector(s) that can deliver the largest quantity of AG while
      being biocompatible. Two liposomes with different surface characteristics
      (cationic and anionic), a LNC and a PNC were prepared. A novel tocopherol
      modified poly(ethylene glycol)-b-polyphosphate block-copolymer was used for the
      first time for the PNC preparation. The NDDSs were compared by their
      physicochemical characteristics, AG release, storage stability, stability in
      serum, complement consumption and toxicity against a human macrovascular
      endothelial cell line (EAhy926). The diameter and surface charge of the NDDSs
      were comparable with previously reported injectable nanocarriers. The NDDSs
      showed good encapsulation efficiency and drug loading. Moreover, the NDDSs were
      stable during storage and in fetal bovine serum for extended periods, showed low
      complement consumption and were non-toxic to EAhy926 cells up to high
      concentrations. Therefore, they can be considered as potential injectable
      nanocarriers of AG. Due to less pronounced burst effect and extended release
      characteristics, the nanocapsules could be favorable approaches for achieving
      prolonged pharmacological activity of AG using injectable NDDS.

PMID- 28456653
TI  - Montmorillonite-lipid hybrid carriers for ionizable and neutral poorly water
      soluble drugs: Formulation, characterization and in vitro lipolysis studies.
AB  - Lipid-based formulations (LBFs) are a popular strategy for enhancing the
      gastrointestinal solubilization and absorption of poorly water-soluble drugs. In
      light of this, montmorillonite-lipid hybrid (MLH) particles, composed of medium
      chain triglycerides, lecithin and montmorillonite clay platelets, have been
      developed as a novel solid-state LBF. Owing to the unique charge properties of
      montmorillonite, whereby the clay platelet surfaces carry a permanent negative
      charge and the platelet edges carry a pH-dependent charge, three model poorly
      water-soluble drugs with different charge properties; blonanserin (weak base, pKa
      7.7), ibuprofen (weak acid, pKa 4.5) and fenofibrate (neutral), were formulated
      as MLH particles and their performance during biorelevant in vitro lipolysis at
      pH 7.5 was investigated. For blonanserin, drug solubilization during in vitro
      lipolysis was significantly reduced 3.4-fold and 3.2-fold for MLH particles in
      comparison to a control lipid solution and silica-lipid hybrid (SLH) particles,
      respectively. It was hypothesized that strong electrostatic interactions between
      the anionic montmorillonite platelet surfaces and cationic blonanserin molecules
      were responsible for the inferior performance of MLH particles. In contrast, no
      significant influence on drug solubilization was observed for ibuprofen- and
      fenofibrate-loaded MLH particles. The results of the current study indicate that
      whilst MLH particles are a promising novel formulation strategy for poorly water
      soluble drugs, drug ionization tendency and the potential for drug-clay
      interactions must be taken into consideration to ensure an appropriate
      performance.

PMID- 28456654
TI  - Aetiologies of cardiac arrest: Seek and ye shall find.

PMID- 28456655
TI  - When and how to freeze: It is all about SPAME!

PMID- 28456656
TI  - "Cardiac arrest-Favorable functional outcome despite high NSE levels and early
      brain swelling".

PMID- 28456657
TI  - Topography of calcium phosphate ceramics regulates primary cilia length and TGF
      receptor recruitment associated with osteogenesis.
AB  - : The surface topography of synthetic biomaterials is known to play a role in
      material-driven osteogenesis. Recent studies show that TGFbeta signalling also
      initiates osteogenic differentiation. TGFbeta signalling requires the recruitment
      of TGFbeta receptors (TGFbetaR) to the primary cilia. In this study, we
      hypothesize that the surface topography of calcium phosphate ceramics regulates
      stem cell morphology, primary cilia structure and TGFbetaR recruitment to the
      cilium associated with osteogenic differentiation. We developed a 2D system using
      two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry.
      One sample had a surface topography at micron-scale (TCP-B, with a bigger surface
      structure dimension) whilst the other had a surface topography at submicron scale
      (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic
      differentiation factors, human bone marrow stromal cells (hBMSCs) were more
      spread on TCP-S than on TCP-B with alterations in actin organization and
      increased primary cilia prevalence and length. The cilia elongation on TCP-S was
      similar to that observed on glass in the presence of osteogenic media and was
      followed by recruitment of transforming growth factor-beta RII (p-TGFbeta RII) to
      the cilia axoneme. This was associated with enhanced osteogenic differentiation
      of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression
      for key osteogenic markers in the absence of additional osteogenic growth
      factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs,
      TCP-S induced bone formation while TCP-B did not. It is most likely that the
      surface topography of calcium phosphate ceramics regulates primary cilia length
      and ciliary recruitment of p-TGFbeta RII associated with osteogenesis and bone
      formation. This bioengineering control of osteogenesis via primary cilia
      modulation may represent a new type of biomaterial-based ciliotherapy for
      orthopedic, dental and maxillofacial surgery applications. STATEMENT OF
      SIGNIFICANCE: The surface topography of synthetic biomaterials plays important
      roles in material-driven osteogenesis. The data presented herein have shown that
      the surface topography of calcium phosphate ceramics regulates mesenchymal
      stromal cells (e.g., human bone marrow mesenchymal stromal cells, hBMSCs) with
      respect to morphology, primary cilia structure and TGFbetaR recruitment to the
      cilium associated with osteogenic differentiation in vitro. Together with bone
      formation in vivo, our results suggested a new type of biomaterial-based
      ciliotherapy for orthopedic, dental and maxillofacial surgery by the
      bioengineering control of osteogenesis via primary cilia modulation.

PMID- 28456658
TI  - The simultaneous inhibition of the mTOR and MAPK pathways with Gnetin-C induces
      apoptosis in acute myeloid leukemia.
AB  - Acute myelogenous leukemia (AML) is a clinically heterogeneous disease that is
      frequently associated with relapse and a poor prognosis. Among the various
      subtypes, AML with the monosomal karyotype (AML-MK) has an extremely unfavorable
      prognosis. We performed screening to identify antitumor compounds that are
      capable of inducing apoptosis in primary leukemia cells harboring the AML-MK
      karyotype and identified a naturally occurring stilbene, Gnetin-C, with potent
      anti-tumor activities against AML cells from patients with various cytogenetic
      abnormalities, including patients with the AML-MK karyotype. Gnetin-C
      simultaneously inhibits the ERK1/2 and the AKT/mTOR pathways, two signals that
      are essential for the survival of leukemia cells. A combination of Gnetin-C with
      low doses of chemotherapeutic drugs led to synergistic anti-tumor effects against
      AML cells. In an immunodeficient mouse model of human leukemia, Gnetin-C
      attenuated the formation of leukemia, depleted leukemia cells and improved
      survival. These findings suggest that Gnetin-C has antitumor activities in AML
      and supports the therapeutic potential of blocking two different pathways in AML.

PMID- 28456659
TI  - N-myc downstream regulated gene 1(NDRG1) promotes the stem-like properties of
      lung cancer cells through stabilized c-Myc.
AB  - Tumor-initiating cells (TICs) play an important role in tumorigenesis and
      development for many various tissue origin cancers including non-small cell lung
      cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely
      unknown. Here, we evaluated differences of mRNA expression between parental and
      oncosphere cells that enriched TICs. We found that N-myc downstream regulated
      gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell
      lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in
      NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4,
      and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC. NDRG1
      prevented the degradation of c-Myc through Skp2-mediated ubiquitination. NDRG1
      directly interacted with Skp2, and decreased phosphorylation of Skp2 through
      inactivation of CDK2. Finally, we confirmed that NDRG1 was negatively correlated
      with survival and prognosis. Thus, our findings indicate that NDRG1 is a
      potential target for eradicating TICs in NSCLC.

PMID- 28456661
TI  - Trichinella Spiralis Impact on Mesenchymal Stem Cells: Immunohistochemical Study
      by Image Analyzer in Murine Model.
AB  - This study aims to elucidate whether Trichinella spiralis infection or its crude
      antigen administration can stimulate recruitment of CD105+ve/CD45-ve cells that
      could represent MSCs in intestine and skeletal muscle of experimental BALB/c
      albino mice compared to healthy control mice. Studied mice were divided into: 20
      healthy control, 20 with orally induced T. spiralis infection, 20 received adult
      worm crude antigen orally and 20 received larval crude antigen intramuscular.
      According to specific timing schedule, mice were sacrificed and tissue sections
      were examined for CD105 and CD45 immunohistochemical expression using image J
      image analyzing software, to compare different study groups. T. spiralis
      infection induced a significant increase in density of CD105+ve/CD45-ve cells
      that could represent MSCs in both intestinal and muscle sections, similarly the
      intramuscular injected larval crude antigen caused more infiltration of such
      cells in muscles compared to muscle sections from healthy control mice. However,
      no significant difference was noticed in intestinal sections after oral adult
      crude antigen administration compared to healthy control mice. So, injected T.
      spiralis crude antigen might be a successful stimulant to MSCs attraction and
      recruitment in tissues nearby injection site. This could be beneficial for cell
      regeneration and tissue repair in case of presence of a disease induced damage.

PMID- 28456660
TI  - Assessing mouse behaviour throughout the light/dark cycle using automated in-cage
      analysis tools.
AB  - An important factor in reducing variability in mouse test outcomes has been to
      develop assays that can be used for continuous automated home cage assessment.
      Our experience has shown that this has been most evidenced in long-term
      assessment of wheel-running activity in mice. Historically, wheel-running in mice
      and other rodents have been used as a robust assay to determine, with precision,
      the inherent period of circadian rhythms in mice. Furthermore, this assay has
      been instrumental in dissecting the molecular genetic basis of mammalian
      circadian rhythms. In teasing out the elements of this test that have determined
      its robustness - automated assessment of an unforced behaviour in the home cage
      over long time intervals - we and others have been investigating whether similar
      test apparatus could be used to accurately discriminate differences in distinct
      behavioural parameters in mice. Firstly, using these systems, we explored
      behaviours in a number of mouse inbred strains to determine whether we could
      extract biologically meaningful differences. Secondly, we tested a number of
      relevant mutant lines to determine how discriminative these parameters were. Our
      findings show that, when compared to conventional out-of-cage phenotyping, a far
      deeper understanding of mouse mutant phenotype can be established by monitoring
      behaviour in the home cage over one or more light:dark cycles.

PMID- 28456662
TI  - New mitogenome and nuclear evidence on the phylogeny and taxonomy of the highly
      zoonotic tapeworm Echinococcus granulosus sensu stricto.
AB  - Cystic echinococcosis, a zoonotic disease caused by Echinococcus granulosus sensu
      lato (s. l.), is a significant global public health concern. Echinococcus
      granulosus s. l. is currently divided into numerous genotypes (G1-G8 and G10) of
      which G1-G3 are the most frequently implicated genotypes in human infections.
      Although it has been suggested that G1-G3 could be regarded as a distinct species
      E. granulosus sensu stricto (s. s.), the evidence to support this is
      inconclusive. Most importantly, data from nuclear DNA that provide means to
      investigate the exchange of genetic material between G1-G3 is lacking as none of
      the published nuclear DNA studies have explicitly included G2 or G3. Moreover,
      the commonly used relatively short mtDNA sequences, including the complete cox1
      gene, have not allowed unequivocal differentiation of genotypes G1-G3. Therefore,
      significantly longer mtDNA sequences are required to distinguish these genotypes
      with confidence. The main aim of this study was to evaluate the phylogenetic
      relations and taxonomy of genotypes G1-G3 using sequences of nearly complete
      mitogenomes (11,443bp) and three nuclear loci (2984bp). A total of 23 G1-G3
      samples were analysed, originating from 5 intermediate host species in 10
      countries. The mtDNA data demonstrate that genotypes G1 and G3 are distinct
      mitochondrial genotypes (separated by 37 mutations), whereas G2 is not a separate
      genotype or even a monophyletic cluster, but belongs to G3. Nuclear data revealed
      no genetic separation of G1 and G3, suggesting that these genotypes form a single
      species due to ongoing gene flow. We conclude that: (a) in the taxonomic sense,
      genotypes G1 and G3 can be treated as a single species E. granulosus s. s.; (b)
      genotypes G1 and G3 should be regarded as distinct genotypes only in the context
      of mitochondrial data; (c) we recommend excluding G2 from the genotype list.

PMID- 28456663
TI  - Comparative whole genome analysis of dengue virus serotype-2 strains differing in
      trans-endothelial cell leakage induction in vitro.
AB  - The role of genetic differences among dengue virus (DENV) in causing increased
      microvascular permeability is less explored. In the present study, we compared
      two closely related DENV serotype-2 strains of Cosmopolitan genotype for their in
      vitro infectivity phenotype and ability to induce trans-endothelial leakage. We
      found that these laboratory strains differed significantly in infecting human
      microvascular endothelial cells (HMEC-1) and hepatocytes (Huh7), two major target
      cells of DENV in in vivo infections. There was a reciprocal correlation in
      infectivity and vascular leakage induced by these strains, with the less
      infective strain inducing more trans-endothelial cell leakage in HMEC-1 monolayer
      upon infection. The cells infected with the strain capable of inducing more
      permeability were found to secrete more Non-Structural protein (sNS1) into the
      culture supernatant. A whole genome analysis revealed 37 predicted amino acid
      changes and changes in the secondary structure of 3' non-translated region
      between the strains. But none of these changes involved the signal sequence coded
      by the C-terminal of the Envelope protein and the two glycosylation sites within
      the NS1 protein critical for its secretion, and the N-terminal NS2A sequence
      important for surface targeting of NS1. The strain that secreted lower levels of
      NS1 and caused less leakage had two mutations within the NS1 protein coding
      region, F103S and T146I that significantly changed amino acid properties. A
      comparison of the sequences of the two strains with published sequences of
      various DENV strains known to cause clinically severe dengue identified a number
      of amino acid changes which could be implicated as possible key genetic
      differences. Our data supports the earlier observations that the vascular leakage
      induction potential of DENV strains is linked to the sNS1 levels. The results
      also indicate that viral genetic determinants, especially the mutations within
      the NS1 coding region, could affect this critical phenotype of DENV strains.

PMID- 28456664
TI  - Identification of the key interactions in structural transition pathway of FtsZ
      from Staphylococcus aureus.
AB  - The tubulin-homolog protein FtsZ is essential for bacterial cell division. FtsZ
      polymerizes to form protofilaments that assemble into a contractile ring-shaped
      structure in the presence of GTP. Recent studies showed that FtsZ treadmilling
      coupled with the GTPase activity drives cell wall synthesis and bacterial cell
      division. The treadmilling caused by assembly and disassembly of FtsZ links to a
      conformational change of the monomer from a tense (T) to a relaxed (R) state, but
      considerable controversy still remains concerning the mechanism. In this study,
      we report crystal structures of FtsZ from Staphylococcus aureus corresponding to
      the T and R state conformations in the same crystal, indicating the structural
      equilibrium of the two state. The two structures identified a key residue Arg29,
      whose importance was also confirmed by our modified MD simulations. Crystal
      structures of the R29A mutant showed T and R state-like conformations with slight
      but important structural changes compared to those of wild-type. Collectively,
      these data provide new insights for understanding how intramolecular interactions
      are related to the structural transition of FtsZ.

PMID- 28456665
TI  - A novel paradigm links mitochondrial dysfunction with muscle stem cell impairment
      in sepsis.
AB  - Sepsis is an acute systemic inflammatory response of the body to microbial
      infection and a life threatening condition associated with multiple organ
      failure. Survivors may display long-term disability with muscle weakness that
      remains poorly understood. Recent data suggest that long-term myopathy in sepsis
      survivors is due to failure of skeletal muscle stem cells (satellite cells) to
      regenerate the muscle. Satellite cells impairment in the acute phase of sepsis is
      linked to unusual mitochondrial dysfunctions, characterized by a dramatic
      reduction of the mitochondrial mass and hyperactivity of residual organelles.
      Survivors maintain the impairment of satellite cells, including alterations of
      the mitochondrial DNA (mtDNA), in the long-term. This condition can be rescued by
      treatment with mesenchymal stem cells (MSCs) that restore mtDNA alterations and
      mitochondrial function in satellite cells, and in fine their regenerative
      potential. Injection of MSCs in turn increases the force of isolated muscle
      fibers and of the whole animal, and improves the survival rate. These effects
      occur in the context of reduced inflammation markers that also raised during
      sepsis. Targeting muscle stem cells mitochondria, in a context of reduced
      inflammation, may represent a valuable strategy to reduce morbidity and long-term
      impairment of the muscle upon sepsis.

PMID- 28456667
TI  - 6 HCV Genotyping 9G test for HCV 1a, 1b, 2, 3, 4 and 6 (6a, 6f, 6i and 6n) with
      high accuracy.
AB  - According to EASL guidelines and WHO recommendations, the accurate detection of
      HCV genotypes such as HCV 1a, HCV1b, HCV 2, HCV 3, HCV 4, and HCV 6 (6a, 6f, 6i,
      6n) is crucial for the efficient treatment of hepatitis C. HCV Genotyping 9G test
      allows simultaneous genotyping of HCV 1a, 1b, 2, 3, 4, and 6 (6a, 6f, 6i, and 6n)
      in clinical samples in 30min. The performance of the test was evaluated by
      comparison with sequence analysis. Serum samples (n=152) from HCV-infected
      patients (n=110) and healthy individuals (n=42) were processed under blinded
      codes. The k coefficient (kappa) values indicated high agreement between the HCV
      Genotyping 9G test and sequencing. The sensitivity and specificity of the test
      were 99.1% and 99.7%, respectively. The results indicate that HCV Genotyping 9G
      test is rapid, reliable, sensitive, and accurate for screening and genotyping of
      HCV in the clinical specimens.

PMID- 28456666
TI  - Heat shock protein 22 (HSPB8) reduces the migration of hepatocellular carcinoma
      cells through the suppression of the phosphoinositide 3-kinase (PI3K)/AKT
      pathway.
AB  - Small heat shock proteins (HSPs) regulate a variety of cell functions. Among
      them, HSP22 and HSP20 are recognized to be ubiquitously expressed in various
      tissues. With regard to hepatocellular carcinoma (HCC) cells, we previously
      reported that phosphorylated HSP20 plays a suppressive role in transforming
      growth factor (TGF)-alpha-induced cell migration and invasion. In the present
      study, we investigated whether or not HSP22 is implicated in HCC cell migration.
      We detected HSP22 protein expression both in human HCC tumor (189.9+/-68.4ng/mg
      protein) and the adjacent non-tumor liver tissues (167.9+/-94.6ng/mg protein).
      The cases of low-quantity HSP22 protein level group (88.3?ng/mg protein, the
      optimum cut-off value of HSP22) were increased in tumor tissues compared with the
      adjacent non-tumor tissues. The migration of human HCC-derived HuH-7 cells
      stimulated by TGF-alpha or hepatocyte growth factor (HGF) was significantly
      enhanced by the knockdown of HSP22 expression. Down-regulation of HSP22 protein
      in the cells markedly strengthened the AKT phosphorylation induced by TGF-alpha
      or HGF. Inhibitors of the phosphoinositide 3-kinase (PI3K)/AKT pathway, which
      suppressed the TGF-alpha-induced migration, significantly reduced the
      amplification by HSP22 knockdown. PI3K but not AKT was coimmunoprecipitated with
      HSP22 in HuH-7 cells. In addition, in human HCC tissues, a significantly lower
      HSP22 protein level in tumor tissues than in adjacent non-tumor tissues was
      observed more frequently in cases of moderately or poorly differentiated HCC than
      well-differentiated HCC. Taken together, our results strongly suggest that HSP22
      represses HCC progression, especially HCC cell migration, by the down-regulation
      of the PI3K/AKT signaling pathway.

PMID- 28456668
TI  - Quantifying low-frequency revertants in oral poliovirus vaccine using next
      generation sequencing.
AB  - Spontaneous reversion to neurovirulence of live attenuated oral poliovirus
      vaccine (OPV) serotype 3 (chiefly involving the n.472U>C mutation), must be
      monitored during production to ensure vaccine safety and consistency. Mutant
      analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC)
      has long been endorsed by the World Health Organization as the preferred in vitro
      test for this purpose; however, it requires radiolabeling, which is no longer
      supported by many laboratories. We evaluated the performance and suitability of
      next generation sequencing (NGS) as an alternative to MAPREC. The linearity of
      NGS was demonstrated at revertant concentrations equivalent to the study range of
      0.25%-1.5%. NGS repeatability and intermediate precision were comparable across
      all tested samples, and NGS was highly reproducible, irrespective of sequencing
      platform or analysis software used. NGS was performed on OPV serotype 3 working
      seed lots and monovalent bulks (n=21) that were previously tested using MAPREC,
      and which covered the representative range of vaccine production. Percentages of
      472-C revertants identified by NGS and MAPREC were comparable and highly
      correlated (r>=0.80), with a Pearson correlation coefficient of 0.95585
      (p<0.0001). NGS demonstrated statistically equivalent performance to that of
      MAPREC for quantifying low-frequency OPV serotype 3 revertants, and offers a
      valid alternative to MAPREC.

PMID- 28456669
TI  - Lumbar muscle structure and function in chronic versus recurrent low back pain: a
      cross-sectional study.
AB  - BACKGROUND CONTEXT: Heterogeneity exists within the low back pain (LBP)
      population. Some patients recover after every pain episode, whereas others suffer
      daily from LBP complaints. Until now, studies rarely make a distinction between
      recurrent low back pain (RLBP) and chronic low back pain (CLBP), although both
      are characterized by a different clinical picture. Clinical experiences also
      indicate that heterogeneity exists within the CLBP population. Muscle
      degeneration, like atrophy, fat infiltration, alterations in muscle fiber type,
      and altered muscle activity, compromises proper biomechanics and motion of the
      spinal units in LBP patients. The amount of alterations in muscle structure and
      muscle function of the paraspinal muscles might be related to the recurrence or
      chronicity of LBP. PURPOSE: The aim of this experimental study is to evaluate
      differences in muscle structure (cross-sectional area and lean muscle fat index)
      and muscle activity of the multifidus (MF) and erector spinae (ES) during trunk
      extension, in patients with RLBP, non-continuous CLBP, and continuous CLBP. STUDY
      DESIGN AND SETTING: This cross-sectional study took place in the university
      hospital of Ghent, Belgium. Muscle structure characteristics and muscle activity
      were assessed by magnetic resonance imaging (MRI). PATIENT SAMPLE: Fifty-five
      adults with non-specific LBP (24 RLBP in remission, 15 non-continuous CLBP, 16
      continuous CLBP) participated in this study. OUTCOME MEASURES: Total cross
      sectional area, muscle cross-sectional area, fat cross-sectional area, lean
      muscle fat index, T2-rest and T2-shift were assessed. METHODS: A T1-weighted
      Dixon MRI scan was used to evaluate spinal muscle cross-sectional area and fat
      infiltration in the lumbar MF and ES. Muscle functional MRI was used to evaluate
      the muscle activity of the lumbar MF and ES during a lumbar extension exercise.
      Before and after the exercise, a pain assessment was performed. This study was
      supported by grants from the Special Research Fund of Ghent University
      (DEF12/AOP/022) without potential conflict of interest-associated biases in the
      text of the paper. RESULTS: Fat cross-sectional area and lean muscle fat index
      were significantly higher in MF and ES in continuous CLBP compared with non
      continuous CLBP and RLBP (p<.05). No differencesbetween groups were found for
      total cross-sectional area and muscle cross-sectional area in MF or ES (p>.05).
      Also, no significant differences between groups for T2-rest were established. T2
      shift, however, was significantly lower in MF and ES in RLBP compared with,
      respectively, non-continuous CLBP and continuous CLBP (p<.05). CONCLUSIONS: These
      results indicate a higher amount of fat infiltration in the lumbar muscles, in
      the absence of clear atrophy, in continuous CLBP compared with RLBP. A lower
      metabolic activity of the lumbar muscles was seen in RLBP replicating a relative
      lower intensity in contractions performed by the lumbar muscles in RLBP compared
      with non-continuous and continuous CLBP. In conclusion, RLBP differs from
      continuous CLBP for both muscle structure and muscle function, whereas non
      continuous CLBP seems comparable with RLBP for lumbar muscle structure and with
      continuous CLBP for lumbar muscle function. These results underline the
      differences in muscle structure and muscle function between different LBP
      populations.

PMID- 28456670
TI  - There is no increased risk of adjacent segment disease at the cervicothoracic
      junction following an anterior cervical discectomy and fusion to C7.
AB  - BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) is a very
      common operative intervention for the treatment of cervical spine degenerative
      disease in those who have failed non-operative measures. However, studies
      examining long-term follow-up on patients who underwent ACDF reveal evidence of
      radiographic and clinical degenerative disc disease at the levels adjacent to the
      fusion construct. Consistent with other junctional regions of the spine, the
      cervicothoracic junction (CTJ) has significant morphologic variations. As a
      result, the CTJ undergoes significant static and dynamic stress. Given these
      findings, there has been some thought that ACDF down to C7 may experience
      additional risks for adjacent segment degeneration/disease (ASD) when compared
      with ASDFs that are cephalad to C7. PURPOSE: The goal of this study is to
      evaluate the rate of radiographic and clinical ASD in patients who have undergone
      single- or multilevel ACDF, down to C7. STUDY DESIGN: This is a retrospective
      cohort study. PATIENT SAMPLE: The sample included consecutive patients from a
      single orthopedic surgeon at one quaternary referral medical center who underwent
      an ACDF between January 2008 and November 2014. Indications for surgery included
      radiculopathy, myelopathy, or myeloradiculopathy in the setting of failed
      conservative treatments. Patients were excluded if they had an ACDF of which the
      caudal level was cephalad to C7 or if they had undergone a previous cervical
      fusion. OUTCOME MEASURES: Radiographic diagnosis of ASD was determined by the
      presence of disc space narrowing >50%, new or enlarged osteophytes, end plate
      sclerosis, or increased calcification of the anterior longitudinal ligament
      (ALL). Postoperatively, data were collected on the presence of new radicular or
      myelopathic symptoms indicative of pathology at C7-T1, indicating a diagnosis of
      clinical ASD. METHODS: Demographic information was collected for all patients,
      which included age, sex, body mass index, smoking status, and Charleston
      Comorbidity Index (CCI). Several radiographic parameters were measured
      preoperatively, immediately postoperatively, and at the last follow-up: C2-C7
      lordosis, sagittal vertical axis (SVA), thoracic inlet angle (TIA), and T1 slope
      C2-C7 lordosis were measured using the Cobb angle between the inferior end plate
      of C2 to the inferior end plate of C7. Radiographic and clinical factors
      associated with ASD were analyzed postoperatively. RESULTS: Four patients (4.8%)
      presented with clinical evidence of ASD, all of whom also showed signs of
      radiographic ASD and improved with conservative measures. No patients underwent
      reoperation for ASD at the C7-T1 junction. Thirty patients (36.1%) presented
      radiographic evidence of ASD. These were generally older (54.4 vs. 48.4 years;
      p=.014). There were neither significant differences in radiographic parameters
      nor between single- versus multilevel ACDFs and the development of ASD.
      CONCLUSIONS: The cervicothoracic junction may present with vulnerability to ASD
      given the junctional biomechanics. However, this study provides evidence that an
      ACDF with the caudal level of C7 does not incur additional risk of ASD, showing
      similar outcomes to ACDFs at other levels.

PMID- 28456671
TI  - Lateral lumbar interbody fusion: a systematic review of complication rates.
AB  - BACKGROUND CONTEXT: Lateral lumbar interbody fusion (LLIF) is a frequently used
      technique for the treatment of lumbar pathology. Despite its overall success,
      LLIF has been associated with a unique set of complications. However, there has
      been inconsistent evidence regarding the complication rate of this approach.
      PURPOSE: To perform a systematic review analyzing the rates of medical and
      surgical complications associated with LLIF. STUDY DESIGN: Systematic review.
      PATIENT SAMPLE: 6,819 patients who underwent LLIF reported in clinical studies
      through June 2016. OUTCOME MEASURES: Frequency of complications within cardiac,
      vascular, pulmonary, urologic, gastrointestinal, transient neurologic, persistent
      neurologic, and spine (MSK) categories. METHODS: This systematic review was
      performed using the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines. Relevant studies that identified rates of any
      complication following LLIF procedures were obtained from PubMed, MEDLINE, and
      EMBASE databases. Articles were excluded if they did not report complications,
      presented mixed complication data from other procedures, or were characterized as
      single case reports, reviews, or case series containing less than 10 patients.
      The primary outcome was frequency of complications within cardiac, vascular,
      pulmonary, urologic, gastrointestinal, transient neurologic, persistent
      neurologic, and MSK categories. All rates of complications were based on the
      sample sizes of studies that mentioned the respective complications. The authors
      report no conflicts of interest directly or indirectly related to this work, and
      have not received any funds in support of this work. RESULTS: A total of 2,232
      articles were identified. Following screening of title, abstract, and full-text
      availability, 63 articles were included in the review. A total of 6,819 patients
      had 11,325 levels fused. The rate of complications for the categories included
      were as follows: wound (1.38%; 95% confidence interval [CI]=1.00%-1.85%), cardiac
      (1.86%; CI=1.33%-2.52%), vascular (0.81%; CI=0.44%-1.36%), pulmonary (1.47;
      CI=0.95%-2.16%), gastrointestinal (1.38%; CI=1.00%-1.87%), urologic (0.93%;
      CI=0.55%-1.47%), transient neurologic (36.07%; CI=34.74%-37.41%), persistent
      neurologic (3.98%; CI=3.42%-4.60%), and MSK or spine (9.22%; CI=8.28%-10.23%).
      CONCLUSIONS: The current study is the first to comprehensively analyze the
      complication profile for LLIFs. The most significant reported complications were
      transient neurologic in nature. However, persistent neurologic complications
      occurred at a much lower rate, bringing into question the significance of
      transient symptoms beyond the immediate postoperative period. Through this
      analysis of complication profiles, surgeons can better understand the risks to
      and expectations for patients following LLIF procedures.

PMID- 28456672
TI  - Muscle localization of heterotopic ossification following spinal cord injury.
AB  - BACKGROUND CONTEXT: Heterotopic ossification (HO) is a known complication
      especially in people with traumatic spinal cord injury (SCI). Although some risk
      factors have already been described, the pathophysiology of HO is still unknown.
      The pelvis is the most common region for HO occurrence. However, the prevalence
      of HO by muscle groups about the hip is not well described. PURPOSE: To analyze
      the prevalence of early HO in muscle groups about the hip in 267 patients with
      SCI. PATIENT SAMPLE: 267 patients with traumatic SCI and pelvic HO. METHODS:
      Between January 2001 and December 2014, 267 patients with SCI were treated in our
      university hospital and were included in the study. Patients were routinely
      screened for HO using ultrasound. The diagnosis of HO was validated using
      magnetic resonance imaging (MRI) or computed tomography (CT). The primary outcome
      measure was the prevalence of HO by muscle groups around the hip. The following
      muscle groups around the hip were defined: (1) gluteal group, (2) adductor group,
      (3) iliopsoas group, and (4) deep muscle group. Additionally, the prevalence of
      concomitant trochanteric bursitis was recorded in all cases. RESULTS: The gluteal
      group showed the highest HO prevalence with 55.8%, followed by the deep muscle
      group with 31.1%. Concomitant trochanteric bursitis was found in 62 patients
      (23.2%). No association between pelvic trauma and HO development was observed
      (n=16, 11%). CONCLUSIONS: The most common muscular location for the occurrence of
      HO about the hip was the gluteal muscle group. Considering that no laboratory
      parameters are currently available for screening for HO, highly sensitive
      ultrasound screening examinations should be routinely performed, with particular
      attention paid to the gluteal muscles. Additionally, routine range of motion
      examination for extension and external rotation of the hip joint is warranted.

PMID- 28456673
TI  - Retrieval and clinical analysis of distraction-based dual growing rod constructs
      for early-onset scoliosis.
AB  - BACKGROUND CONTEXT: Growing rod constructs are an important contribution for
      treating patients with early-onset scoliosis. These devices experience high
      failure rates, including rod fractures. PURPOSE: The objective of this study was
      to identify the failure mechanism of retrieved growing rods, and to identify
      differences between patients with failed and intact constructs. STUDY
      DESIGN/SETTING: Growing rod patients who had implant removal and were previously
      enrolled in a multicenter registry were eligible for this study. PATIENT SAMPLE:
      Forty dual-rod constructs were retrieved from 36 patients across four centers,
      and 34 of those constructs met the inclusion criteria. Eighteen constructs failed
      due to rod fracture. Sixteen intact constructs were removed due to final fusion
      (n=7), implant exchange (n=5), infection (n=2), or implant prominence (n=2).
      OUTCOME MEASURES: Analyses of clinical registry data, radiographs, and retrievals
      were the outcome measures. METHODS: Retrievals were analyzed with microscopic
      imaging (optical and scanning electron microscopy) for areas of mechanical
      failure, damage, and corrosion. Failure analyses were conducted on the fracture
      surfaces to identify failure mechanism(s). Statistical analyses were performed to
      determine significant differences between the failed and intact groups. RESULTS:
      The failed rods fractured due to bending fatigue under flexion motion. Construct
      configuration and loading dictate high bending stresses at three distinct
      locations along the construct: (1) mid-construct, (2) adjacent to the tandem
      connector, or (3) adjacent to the distal anchor foundation. In addition, high
      torques used to insert set screws may create an initiation point for fatigue.
      Syndromic scoliosis, prior rod fractures, increase in patient weight, and rigid
      constructs consisting of tandem connectors and multiple crosslinks were
      associated with failure. CONCLUSION: This is the first study to examine
      retrieved, failed growing rod implants across multiple centers. Our analysis
      found that rod fractures are due to bending fatigue, and that stress
      concentrations play an important role in rod fractures. Recommendations are made
      on surgical techniques, such as the use of torque-limiting wrenches or not
      exceeding the prescribed torques. Additional recommendations include frequent rod
      replacement in select patients during scheduled surgeries.

PMID- 28456674
TI  - Bone morphogenetic protein use in spine surgery in the United States: how have we
      responded to the warnings?
AB  - BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has
      been widely adopted as a fusion adjunct in spine surgery since its approval in
      2002. A number of concerns regarding adverse effects and potentially devastating
      complications of rhBMP-2 use led to a Food and Drug Administration (FDA) advisory
      issued in 2008 cautioning its use, and a separate warning about its potential
      complications was published by The Spine Journal in 2011. PURPOSE: To compare
      trends of rhBMP-2 use in spine surgery after the FDA advisory in 2008 and The
      Spine Journal warning in 2011. STUDY DESIGN: Retrospective cross-sectional study
      using a national database. PATIENT SAMPLE: All patients from 2002 to 2013 who
      underwent spinal fusion surgery at an institution participating in the Nationwide
      Inpatient Sample (NIS). OUTCOME MEASURES: Proportion of spinal fusion surgeries
      using rhBMP-2. METHODS: We queried the NIS from 2002 to 2013 and used
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) procedure codes to identify spinal fusion procedures and those that
      used rhBMP-2. Procedures were subdivided into primary and revision fusions, and
      by region of the spine. Cervical and lumbosacral fusions were further stratified
      into anterior and posterior approaches. The percentage of cases using BMP was
      plotted across time. A linear regression was fit to the data from quarter 3 of
      2008 (FDA advisory) through quarter 1 of 2011, and a separate regression was fit
      to the data from quarter 2 of 2011 (The Spine Journal warning) onward. The slopes
      of these regression lines were statistically compared to determine differences in
      trends. No funding was received to conduct this study, and no authors had any
      relevant conflicts of interest. RESULTS: A total of 4,167,079 patients in the NIS
      underwent spinal fusion between 2002 and 2013. We found a greater decrease in
      rhBMP-2 use after The Spine Journal warning compared with the FDA advisory for
      all fusion procedures (p=.006), primary fusions (p=.006), and revision fusions
      (p=.004). Lumbosacral procedures also experienced a larger decline in rhBMP-2 use
      after The Spine Journal article as compared with the FDA warning (p=.0008). This
      pattern was observed for both anterior and posterior lumbosacral fusions
      (p<=.0001 for both). Anterior cervical fusion was the only procedure that
      demonstrated a decline in rhBMP-2 use after the FDA advisory that was
      statistically greater than after The Spine Journal article (p=.02). CONCLUSIONS:
      Warnings sanctioned through the spine literature may have a greater influence on
      practice of the spine surgery community as compared with advisories issued by the
      FDA.Comprehensive guidelines regarding safe and effective use of rhBMP-2 must be
      established.

PMID- 28456675
TI  - Stability-preserving decompression in degenerative versus congenital spinal
      stenosis: demographic patterns and patient outcomes.
AB  - BACKGROUND CONTEXT: Although lumbar spinal stenosis often presents as a
      degenerative condition (degenerative stenosis [DS]), some patients present with
      symptoms from lifelong narrowing of the spinal canal. These patients have
      congenital stenosis (CS) and present with symptoms of stenosis at a younger age.
      Patients with CS often have a distinct pathophysiology with fewer degenerative
      changes but present with multilevel involvement. In the setting of neurologic
      symptoms, decompression alone while preserving stability has been proposed for
      both patient populations. PURPOSE: The purpose of this study is to evaluate if
      the different etiology for narrowing in CS and DS results in a different natural
      history of pain progression, different locations requiring decompression, and
      different outcomes following a stability-preserving decompression procedure.
      STUDY DESIGN/SETTING: This study used a retrospective cohort study patient
      sample: We retrospectively reviewed consecutive patients of a single surgeon with
      DS or CS who underwent surgical decompression without fusion between 2008 and
      2014. Patients were excluded if they had undergone a previous lumbar surgical
      procedure (decompression or fusion) or follow-up less than 12 months. OUTCOME
      MEASURES: Pre- and postoperative clinical outcome scores including visual
      analogue scale (VAS) and Oswestry Disability Index (ODI) were recorded.
      Postoperatively, data were collected regarding complications, the presence of new
      radicular or myelopathic symptoms, and necessity of reoperation in the lumbar
      spine. METHODS: Demographic information included age, sex, body mass index,
      smoking status, and Charleston Comorbidity Index (CCI). Preoperative clinical
      symptoms as well as the presence of lower extremity radiculopathy and
      claudication were evaluated. Patients were determined to have a diagnosis of CS
      by the treating surgeon if primary radiographs revealed shortened pedicles and
      decreased cross-sectional area of the spinal canal as detailed by previous
      studies. Binary outcomes were compared between congenital and degenerative
      cohorts using bivariate and multivariate logistic regression. Multivariate
      regressions controlled for baseline patient and operative characteristics.
      RESULTS: The average age of the DS cohort was 66.7+/-10.7 years, whereas for the
      CS group, it was 47.1+/-9.2 years. Average follow-up was 27.6 months. The
      patients with DS had significantly more comorbidities as shown by the CCI score
      (2.8+/-1.6 vs. 0.5+/-0.6); p<.001) and the American Society of Anesthesiologists
      (ASA) score >=3 (52.8% vs. 11.1%; p<.001). Patients with CS presented with higher
      VAS back (8.0 vs. 5.1; p=.008) and leg (7.9 vs. 4.5; p<.001) scores. Patients
      with DS presented with significantly greater duration of preoperative back pain
      and leg pain (42.7 vs. 30.5 months; p=.042). Postoperatively, there were no
      significant differences in VAS back, leg, or ODI scores. However, a trend toward
      a lower VAS leg score was present in the patients with CS when compared with
      patients with DS (2.6+/-3.0 vs. 4.2+/-3.2; p<.117). Both patient groups
      experienced similar levels of symptomatic relief and improvement in VAS and ODI
      scores. There were no significant differences in new-onset radicular symptoms
      requiring conservative treatment or reoperation. In both groups combined, 81.9%
      of patients reported resolution of lower extremity symptoms at final follow-up.
      Overall, 20.6% of patients experienced new lower-extremity radicular symptoms
      after a period of resolution of symptoms postoperatively. There were
      significantly more reoperations following surgical decompression in patients with
      DS (13.9% vs. 2.8%; p=.02). CONCLUSIONS: Patients with CS and patients with DS
      respond well to decompression alone, without a supplemental fusion, despite
      differences in pain experience and presentation. The localization of pathology
      requiring decompression is similar. The patients with DS were more susceptible to
      require another operation resulting in a fusion, which confirms the theory that
      initial microinstability can progress in DS, but is likely not part of the
      disease process in CS. At just over 2 years after decompression, patients with CS
      may not need to be treated by a fusion in the setting of lower back pain;
      however, longer-term follow up is necessary to further assess these outcomes.

PMID- 28456676
TI  - Early intervention in cauda equina syndrome associated with better outcomes: a
      myth or reality? Insights from the Nationwide Inpatient Sample database (2005
      2011).
AB  - BACKGROUND CONTEXT: Evidence-based consensus on timing to surgical decompression
      following symptom onset in patients with cauda equina syndrome (CES) is limited
      or widely debated. PURPOSE: This study aimed to investigate whether timing to
      intervention in the management of patients with CES has an impact on outcomes.
      STUDY DESIGN/SETTING: This is a retrospective cohort study. PATIENT SAMPLE: The
      patient sample included 4,066 adult patients with CES registered in the
      Nationwide Inpatient Sample database (2005-2011) and undergoing elective
      decompression surgery. OUTCOME MEASURES: The outcome measures are inpatient
      mortality, unfavorable discharge (discharge to rehabilitation), prolonged length
      of stay (LOS>75th percentile), and high hospital charges in patients undergoing
      decompression for CES. METHODS: The patients were stratified into three
      categories based on timing to surgical intervention: (1) within 24 hours
      (n=1,846, 45.6%); (2) between 24 and 48 hours (n=1,080, 26.6%), and (3) beyond 48
      hours (n=1,130, 27.8%). Multivariable logistic regression fitted with generalized
      estimating equations using the sandwich variance-covariance matrix estimator to
      account for the clustering of similar outcomes within hospitals was used to
      examine the association of timing to surgical intervention categories with binary
      primary end points. For metric end points (charges), we used the ordinary least
      squares model to test the effect of timing to intervention. RESULTS: The mean age
      of the cohort was 50.19+/-17.55 years and 41% were female. In comparison to
      patients operated within 24 hours, increased likelihood of inpatient mortality
      (odds ratio [OR]: 3.61, 95% confidence interval [CI]: 1.32-9.85, p=.012),
      unfavorable discharge (OR: 2.23, 95% CI: 1.87-2.66, p<.001), prolonged
      postsurgical LOS (OR: 1.76, 95% CI: 1.44-2.14, p<.001), and high hospital charges
      (OR:1.92, 95% CI: 1.81-2.05, p<.001) were observed in patients operated on over
      48 hours since admission. Likewise, patients with incomplete CES with
      intervention beyond 48 hours had higher odds for unfavorable discharge (OR: 2.51,
      95% CI: 1.99-3.17, p<.001), prolonged postsurgical LOS (OR: 1.73, 95% CI: 1.35
      2.20, p<.001), and high hospital charges (OR: 1.94, 95% CI: 1.79-2.10, p<.001).
      Likewise, patients with complete CES with interventions beyond 48 hours had
      higher odds for unfavorable discharge (OR: 1.86, 95% CI: 1.41-2.45, p<.001),
      prolonged postsurgical LOS (OR: 2.06, 95% CI: 1.53-2.77, p<.001), and high
      hospital charges (OR: 1.39, 95% CI: 1.15-1.68, p<.001). CONCLUSIONS: Early
      intervention in CES, regardless of the subtype (complete or incomplete), has
      higher likelihood of improved inpatient outcomes. The odds of getting better were
      higher, however, with incomplete CES. The timing of intervention did not seem to
      matter in traumatic CES as compared with degenerative etiology. Prospective
      randomized controlled trials may further help elucidate the impact of early
      intervention on outcomes in patients with CES.

PMID- 28456677
TI  - Kinematic evaluation of cervical sagittal balance and thoracic inlet alignment in
      degenerative cervical spondylolisthesis using kinematic magnetic resonance
      imaging.
AB  - BACKGROUND CONTEXT: T1 slope is a novel thoracic parameter used to assess
      cervical spine sagittal balance. Thoracic index (TI) parameters including T1
      slope and cervical sagittal alignment parameters may play an important role in
      degenerative cervical spondylolisthesis (DCS). Current literature regarding the
      relationship between TI and cervical sagittal alignment parameters in patients
      with DCS is limited. PURPOSE: (1) To evaluate the T1 slope, cervical sagittal
      alignment, and thoracic inlet parameter in patients with DCS using kinematic
      magnetic resonance imaging (kMRI), and (2) to find a correlation between the T1
      slope, TI, and other cervical sagittal parameters in patients with DCS.
      DESIGN/SETTING: Retrospective kMRI study, Level III. PATIENT SAMPLE: Fifty-two
      patients with DCS from 1,128 patients from a cervical kMRI database. OUTCOME
      MEASURES: T1 slope, C2-C7 angle, sagittal vertical axis C2-C7 (SVA C2-C7),
      cranial tilt, cervical tilt, neck tilt, and thoracic inlet angle (TIA). METHODS:
      Cervical spine kMRIs of 52 patients with DCS (mean age 51.7+/-standard deviation)
      were analyzed in neutral, flexion, and extension positions. Patients with DCS
      were divided into two groups: anterolisthesis (N=33) and retrolisthesis (N=19).
      Each listhesis group was subclassified into grade 1 (slip 2-3 mm) and grade 2
      (slip>3 mm). RESULTS: Grade 2 retrolisthesis had the largest T1 slope followed by
      grade 1 retrolisthesis, grade 2 anterolisthesis, and grade 1 anterolisthesis.
      Significant differences were found between the anterolisthesis and the
      retrolisthesis groups in the neutral position (p=.025). The flexion position had
      the largest T1 slope and showed a significant difference with anterolisthesis in
      the neutral position (p=.041). Sagittal vertical axis C2-C7 showed strong
      correlation with cranial tilt in all DCS groups and all positions. CONCLUSIONS:
      In our study, T1 slope was larger in grade 2 DCS, and the retrolisthesis group
      had larger T1 slope than the anterolisthesis group. Presence of larger T1 slope
      was significantly correlated with larger cervical lordosis curvature.
      Furthermore, cranial tilt was strongly correlated with SVA C2-C7.

PMID- 28456678
TI  - Long-term regulation of gene expression in muscle cells by systemically delivered
      siRNA.
AB  - Many muscular dystrophies, including lethal Duchenne muscular dystrophy, are
      incurable and require the sustained application of drugs that have only minor
      treatment effects and serious negative side effects. The mechanism of siRNA
      mediated transcriptional gene regulation (TGR) appears to have a long-lasting
      effect and may be a viable solution to treat muscle disorders because single or
      at least rarely repeated therapies would be used. For the best results, siRNA
      should be delivered to all disease affected muscles, and systemic delivery of
      siRNA through blood vessels is probably the only applicable choice to achieve
      this goal. Unfortunately, there are many challenges to overcome such as siRNA
      degradation in blood, renal clearance, blood-muscle barrier, cell entry and
      endosomal escape. By exploiting and considering the unique features of muscles
      and the mechanism of TGR, we will discuss the possible ways to induce TGR in
      muscles by using non-viral systemic siRNA delivery methods.

PMID- 28456679
TI  - Assembly of polymer micelles through the sol-gel transition for effective cancer
      therapy.
AB  - Photo-induced apoptosis-targeted chemotherapy (PIATC) was designed and
      characterized to propose a new protocol for improved chemotherapy. Intratumoral
      injection was selected as the mode of administration of the anticancer drug,
      doxorubicin (DOX). To extend the retention time of DOX at the tumor parenchyma,
      in-situ gel formation was induced through the sol-gel transition of the Pluronic
      NPs containing a prodrug of DOX or a photosensitizer. The prodrug (DEVD-S-DOX)
      was designed to be inactive with a peptide moiety (Aspartic acid-Glutamic acid
      Valine-Aspartic acid: DEVD) linked to DOX and to be cleaved into free DOX by
      caspase-3 expressed with apoptosis. For reactive oxygen species (ROS)-mediated
      apoptosis, photo-irradiation with methylene blue (MB, photosensitizer) was
      utilized. The sol-gel transition of the Pluronic NPs containing reactive species,
      DEVD-S-DOX or MB, was examined by measuring the cloud point and the gel strength
      in response to temperature change. ROS-mediated apoptosis was observed by
      measuring the ROS and membrane integrity with induced apoptosis. The in vivo
      antitumor efficacy of PIATC was measured with a cardiotoxicity assay in tumor
      bearing mice.

PMID- 28456680
TI  - Splicing regulatory factors, ageing and age-related disease.
AB  - Alternative splicing is a co-transcriptional process, which allows for the
      production of multiple transcripts from a single gene and is emerging as an
      important control point for gene expression. Alternatively expressed isoforms
      often have antagonistic function and differential temporal or spatial expression
      patterns, yielding enormous plasticity and adaptability to cells and increasing
      their ability to respond to environmental challenge. The regulation of
      alternative splicing is critical for numerous cellular functions in both
      pathological and physiological conditions, and deregulated alternative splicing
      is a key feature of common chronic diseases. Isoform choice is controlled by a
      battery of splicing regulatory proteins, which include the serine arginine rich
      (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes.
      These important splicing regulators have been implicated in age-related disease,
      and in the ageing process itself. This review will outline the important
      contribution of splicing regulator proteins to ageing and age-related disease.

PMID- 28456681
TI  - Early coronary calcifications are related to cholesterol burden in heterozygous
      familial hypercholesterolemia.
AB  - BACKGROUND: The identification of high-risk patients with heterozygous familial
      hypercholesterolemia (HeFH) that may benefit from early treatment is challenging.
      Coronary Artery Calcification (CAC) score accounts for coronary atherosclerotic
      burden. It has proven its accuracy in cardiovascular risk assessment in the
      general population but data in HeFH are lacking. OBJECTIVE: The aim of our study
      was to assess CAC prevalence and its relationship with lifelong cholesterol
      exposure, calculated by total cholesterol burden (TCB) in patients with HeFH.
      METHODS: A total of 112 HeFH patients (50% males, median age 45 years) regularly
      followed-up since diagnosis were prospectively recruited at Pitie-Salpetriere
      Hospital, Paris, France. CAC score was assessed using noncontrast multi-detector
      computed tomography. TCB was calculated as total cholesterol (TC) * age at
      diagnosis plus annually assessed TC. RESULTS: The prevalence of CAC was 58%.
      Patients without CAC showed lower TCB than patients with CAC (298 +/- 110 vs
      417.9 +/- 89 mmol-years/L, P < .001). Among patients aged <45 years (n = 56), 39%
      exhibited CAC and a higher TCB compared with patients without CAC (352 +/- 71 vs
      255 +/- 88 mmol-years/L, P < .001) due to higher TC levels at diagnosis (10.2 +/-
      2 vs 8.7 +/- 2 mmol/L, P = .01). Multivariate analysis indicated that TCB was
      independently associated to CAC. CONCLUSIONS: Asymptomatic HeFH subjects exhibit
      early coronary atherosclerosis directly associated with TCB burden. CAC score may
      be useful to identify higher risk HeFH patients who can benefit from earlier and
      more aggressive treatment.

PMID- 28456682
TI  - Polygenic risk score predicts prevalence of cardiovascular disease in patients
      with familial hypercholesterolemia.
AB  - BACKGROUND: Although familial hypercholesterolemia (FH) is a severe monogenic
      disease, it has been shown that clinical risk factors and common genetic variants
      can modify cardiovascular disease (CVD) risk. OBJECTIVE: The aim of the study was
      to evaluate the polygenic contribution to lipid traits and CVD in FH using
      genetic risk scores (GRSs). METHODS: Among the 20,434 subjects attending the
      lipid clinic, we identified and included 725 individuals who carried an FH
      causing mutation in this retrospective cohort study. We evaluated the association
      of GRSs for several traits including coronary artery disease (CAD; GRSCAD) as
      well as plasma concentrations of low-density lipoprotein cholesterol (LDL-C;
      GRSLDL-C), high-density lipoprotein cholesterol (GRSHDL-C) and triglycerides
      (GRSTG). RESULTS: A total of 32% (n = 231) of FH subjects presented a CVD event
      before their first visit. Patients in the highest GRSLDL-C tertile presented an
      LDL-C 0.4 mmol/L (15.5 mg/dL) higher than the subjects in the lowest tertile (P =
      .01). The GRSCAD was strongly associated with CVD events (odds ratio 1.80; 95%
      confidence interval 1.14-2.85; P = .01) even after adjustment for cardiovascular
      risk factors. Compared with subjects in the first tertile, those in the third
      GRSCAD tertile had a significantly higher prevalence of events (40.9% vs 24.7%, P
      < .0001) and a significantly higher number of events (average 0.97 vs 0.57 [P =
      .0001] events per individual). CONCLUSION: These results indicate that even in
      the context of a severe monogenic disease such as FH, common genetic variants can
      significantly modify the disease phenotype. The use of the 192-SNPs GRSCAD may
      refine CVD risk prediction in FH patients and this could lead to a more
      personalized approach to therapy.

PMID- 28456683
TI  - Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis
      and suppresses tryptophan catabolism.
AB  - Despite the increased morbidity of ulcerative colitis (UC) in recent years,
      available treatments remain unsatisfactory. Pogostemon cablin has been widely
      applied to treat a variety of gastrointestinal disorders in clinic for centuries,
      in which patchouli alcohol (PA, C15H26O) has been identified as the major active
      component. This study attempted to determine the bioactivity of PA on dextran
      sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action.
      Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given
      PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via
      oral administration for 7 days. At the end of study, animals were sacrificed and
      samples were collected for pathological and other analysis. In addition, a
      metabolite profiling and a targeted metabolite analysis, based on the Ultra
      Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS)
      approach, were performed to characterize the metabolic changes in plasma. The
      results revealed that PA significantly reduced the disease activity index (DAI)
      and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and
      cytokines involving TNF-alpha, IFN-gamma, IL-1beta, IL-6, IL-4 and IL-10 also
      declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing
      the level of colonic expression of the tight junction (TJ) proteins, for instance
      ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and
      mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell
      death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and
      down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up
      regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by
      PA, which was in line with the declined levels of kynurenine (Kyn) and 5
      hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently
      reduced when Kyn was given to mice. In summary, the study successfully
      demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing
      inflammation, maintaining the integrity of intestinal epithelial barrier,
      inhibiting cell death signaling, and suppressing tryptophan catabolism. The
      results provided valuable information and guidance for using PA in treatment of
      UC.

PMID- 28456684
TI  - Trend analysis of imported malaria in London; observational study 2000 to 2014.
AB  - BACKGROUND: We describe trends of malaria in London (2000-2014) in order to
      identify preventive opportunities and we estimated the cost of malaria admissions
      (2009/2010-2014/2015). METHODS: We identified all cases of malaria, resident in
      London, reported to the reference laboratory and obtained hospital admissions
      from Hospital Episode Statistics. RESULTS: The rate of malaria decreased
      (19.4[2001]-9.1[2014] per 100,000). Males were over-represented (62%). Cases in
      older age groups increased overtime. The rate was highest amongst people of Black
      African ethnicity followed by Indian, Pakistani, Bangladeshi ethnicities combined
      (103.3 and 5.5 per 100,000, respectively). The primary reason for travel was
      visiting friends and relatives (VFR) in their country of origin (69%), mostly sub
      Saharan Africa (92%). The proportion of cases in VFRs increased (32%[2000]
      50%[2014]) and those taking chemoprophylaxis decreased (36%[2000]-14%[2014]). The
      overall case fatality rate was 0.3%. We estimated the average healthcare cost of
      malaria admissions to be just over L1 million per year. CONCLUSION: Our study
      highlighted that people of Black African ethnicity, travelling to sub-Saharan
      Africa to visit friends and relatives in their country of origin remain the most
      affected with also a decline in chemoprophylaxis use. Malaria awareness should
      focus on this group in order to have the biggest impact but may require new
      approaches.

PMID- 28456685
TI  - Association of regulatory TPH2 polymorphisms with higher reduction in depressive
      symptoms in children and adolescents treated with fluoxetine.
AB  - Genetic variability related to the brain serotonergic system has a significant
      impact on both the susceptibility to psychiatric disorders, such as major
      depressive disorder (MDD), and the response to antidepressant drugs, such as
      fluoxetine. TPH2 is one of the most important serotonergic candidate genes in
      selective serotonin reuptake inhibitors (SSRIs) pharmacogenetic studies. The aim
      of the present study was to evaluate the influence of regulatory polymorphisms
      that are specifically located in human TPH2 transcription factor binding sites
      (TFBSs), and therefore could be functional by altering gene expression, on
      clinical improvement in children and adolescents treated with fluoxetine. The
      selection of SNPs was also based on their linkage disequilibrium with TPH2
      rs4570625, a genetic variant with questionable functionality, which was
      previously associated with clinical response in our pediatric population. A total
      of 83 children and adolescents were clinically evaluated 12weeks after initiating
      antidepressant treatment with fluoxetine for the first time. Clinical improvement
      was assessed by reductions in depressive symptoms measured using the Children's
      Depression Inventory (CDI) scale. The polymorphisms rs11179002, rs60032326 and
      rs34517220 were, for the first time in the literature, significantly associated
      with higher clinical improvement. The strongest association was found for
      rs34517220. In particular, minor allele homozygotes showed higher score
      reductions on the CDI scale compared with the major allele carriers.
      Interestingly, this polymorphism is located in a human TPH2 TFBS for two relevant
      transcription factors in the serotoninergic neurons, Foxa1 and Foxa2, which
      together with the high level of significance found for this SNP, could indicate
      that rs34517220 is in fact the crucial functional genetic variant related to the
      fluoxetine response. These results provide new evidence for the role of
      regulatory genetic variants that could modulate human TPH2 expression in the SSRI
      antidepressant response.

PMID- 28456686
TI  - The dual modulatory effects of efavirenz on GABAA receptors are mediated via two
      distinct sites.
AB  - Efavirenz is a widely prescribed medicine used to treat type 1 human
      immunodeficiency virus (HIV-1), the most prevalent pathogenic strain of the virus
      responsible for the acquired immune deficiency syndrome (AIDS) pandemic. Under
      prescribed dosing conditions, either alone or in combination therapy, efavirenz
      induced CNS disturbances are frequently reported. Efavirenz was recently reported
      to interact in a similar concentration range with a number of receptors,
      transporters and ion channels including recombinant rat alpha1beta2gamma2 GABAA
      receptors whose actions were potentiated (Gatch et al., 2013; Dalwadi et al.,
      2016). Now we report on the molecular mechanism of efavirenz on GABAA receptors
      as a function of concentration and subunit composition via whole-cell recordings
      of GABA-activated currents from HEK293 cells expressing varying subunit
      configurations of GABAA receptors. Efavirenz elicited dual effects on the GABA
      response; it allosterically potentiated currents at low concentrations, whereas
      it inhibited currents at higher concentrations. The allosteric potentiating
      action on GABAA receptors was pronounced in the alpha1beta2gamma2,
      alpha2beta2gamma2 and alpha4beta2gamma2 configurations, greatly diminished in the
      alpha6beta2gamma2 configuration, and completely absent in the alpha3beta2gamma2
      or alpha5beta2gamma2 configuration. In stark contrast, the inhibitory modulation
      of efavirenz at higher concentrations was evident in all subunit configurations
      examined. Moreover, efavirenz-induced modulatory effects were dependent on GABA
      concentration ([GABA]), with a pronounced impact on currents activated by low
      [GABA] but little effect at saturating [GABA]. Mutation of a highly-conserved
      threonine to phenylalanine in transmembrane domain 2 of the alpha1 subunit
      abolished the inhibitory effect of efavirenz in alpha1beta2 receptors. Finally,
      mutations of any of the three conserved extracellular residues in alpha1/2/4
      subunits to the conserved residues at the corresponding positions in alpha3/5
      subunits (i.e., R84P, M89L or I120L) completely eliminated the potentiating
      effect of efavirenz in alpha1beta2gamma2 configuration. These findings
      demonstrate that efavirenz's positive allosteric modulation of the GABAA receptor
      is mediated via a novel allosteric site associated with the extracellular domain
      of the receptor.

PMID- 28456688
TI  - Native metabotropic glutamate receptor 4 depresses synaptic transmission through
      an unusual Galphaq transduction pathway.
AB  - In cerebellar cortex, mGlu4 receptors located on parallel fibers play an
      essential role in normal motor function, but the molecular mechanisms involved
      are not yet completely understood. Using a strategy combining biochemical and
      electrophysiological approaches in the rodent cerebellum, we demonstrate that
      presynaptic mGlu4 receptors control synaptic transmission through an atypical
      activation of Galphaq proteins. First, the Galphaq subunit, PLC and PKC signaling
      proteins present in cerebellar extracts are retained on affinity chromatography
      columns grafted with different sequences of the cytoplasmic domain of mGlu4
      receptor. The i2 loop and the C terminal domain were used as baits, two domains
      that are known to play a pivotal role in coupling selectivity and efficacy.
      Second, in situ proximity ligation assays show that native mGlu4 receptors and
      Galphaq subunits are in close physical proximity in cerebellar cortical slices.
      Finally, electrophysiological experiments demonstrate that the molecular
      mechanisms underlying mGlu4 receptor-mediated inhibition of transmitter release
      at cerebellar Parallel Fiber (PF) - Molecular Layer Interneuron (MLI) synapses
      involves the Galphaq-PLC signaling pathway. Taken together, our results provide
      compelling evidence that, in the rodent cerebellar cortex, mGlu4 receptors act by
      coupling to the Galphaq protein and PLC effector system to reduce glutamate
      synaptic transmission.

PMID- 28456687
TI  - Oxytocin receptor neurotransmission in the dorsolateral bed nucleus of the stria
      terminalis facilitates the acquisition of cued fear in the fear-potentiated
      startle paradigm in rats.
AB  - Oxytocin (OT) is a hypothalamic neuropeptide that modulates fear and anxiety-like
      behaviors. Dorsolateral bed nucleus of the stria terminalis (BNSTdl) plays a
      critical role in the regulation of fear and anxiety, and expresses high levels of
      OT receptor (OTR). However, the role of OTR neurotransmission within the BNSTdl
      in mediating these behaviors is unknown. Here, we used adult male Sprague-Dawley
      rats to investigate the role of OTR neurotransmission in the BNSTdl in the
      modulation of the acoustic startle response, as well as in the acquisition and
      consolidation of conditioned fear using fear potentiated startle (FPS) paradigm.
      Bilateral intra-BNSTdl administration of OT (100 ng) did not affect the
      acquisition of conditioned fear response. However, intra-BNSTdl administration of
      specific OTR antagonist (OTA), (d(CH2)51, Tyr(Me)2, Thr4, Orn8, des-Gly-NH29)
      vasotocin, (200 ng), prior to the fear conditioning session, impaired the
      acquisition of cued fear, without affecting a non-cued fear component of FPS.
      Neither OTA, nor OT affected baseline startle or shock reactivity during fear
      conditioning. Therefore, the observed impairment of cued fear after OTA infusion
      resulted from the specific effect on the formation of cued fear. In contrast to
      the acquisition, neither OTA nor OT affected the consolidation of FPS, when
      administered after the completion of fear conditioning session. Taken together,
      these results reveal the important role of OTR neurotransmission in the BNSTdl in
      the formation of conditioned fear to a discrete cue. This study also highlights
      the role of the BNSTdl in learning to discriminate between threatening and safe
      stimuli.

PMID- 28456689
TI  - A novel method for quantitative measurements of gene expression in single living
      cells.
AB  - Gene expression is at the heart of virtually any biological process, and its
      deregulation is at the source of numerous pathological conditions. While
      impressive progress has been made in genome-wide measurements of mRNA and protein
      expression levels, it is still challenging to obtain highly quantitative
      measurements in single living cells. Here we describe a novel approach based on
      internal tagging of endogenous proteins with a reporter allowing luminescence and
      fluorescence time-lapse microscopy. Using luminescence microscopy, fluctuations
      of protein expression levels can be monitored in single living cells with high
      sensitivity and temporal resolution over extended time periods. The integrated
      protein decay reporter allows measuring protein degradation rates in the absence
      of protein synthesis inhibitors, and in combination with absolute protein levels
      allows determining absolute amounts of proteins synthesized over the cell cycle.
      Finally, the internal tag can be excised by inducible expression of Cre
      recombinase, which enables to estimate endogenous mRNA half-lives. Our method
      thus opens new avenues in quantitative analysis of gene expression in single
      living cells.

PMID- 28456690
TI  - Standardization of DNA extraction from sand flies: Application to genotyping by
      next generation sequencing.
AB  - Standardization of the methods for extraction of DNA from sand flies is essential
      for obtaining high efficiency during subsequent molecular analyses, such as the
      new sequencing methods. Information obtained using these methods may contribute
      substantially to taxonomic, evolutionary, and eco-epidemiological studies. The
      aim of the present study was to standardize and compare two methods for the
      extraction of genomic DNA from sand flies for obtaining DNA in sufficient
      quantities for next-generation sequencing. Sand flies were collected from the
      municipalities of Campo Grande, Camapua, Corumba and Miranda, state of Mato
      Grosso do Sul, Brazil. Three protocols using a silica column-based commercial kit
      (ReliaPrepTM Blood gDNA Miniprep System kit, Promega(r)), and three protocols
      based on the classical phenol-chloroform extraction method (Uliana et al., 1991),
      were compared with respect to the yield and quality of the extracted DNA. DNA was
      quantified using a Qubit 2.0 fluorometer. The presence of sand fly DNA was
      confirmed by PCR amplification of the IVS6 region (constitutive gene), followed
      by electrophoresis on a 1.5% agarose gel. A total of 144 male specimens were
      analyzed, 72 per method. Significant differences were observed between the two
      methods tested. Protocols 2 and 3 of phenol-chloroform extraction presented
      significantly better performance than all commercial kit extraction protocols
      tested. For phenol-chloroform extraction, protocol 3 presented significantly
      better performance than protocols 1 and 2. The IVS6 region was detected in 70 of
      72 (97.22%) samples extracted with phenol, including all samples for protocols 2
      and 3. This is the first study on the standardization of methods for the
      extraction of DNA from sand flies for application to next-generation sequencing,
      which is a promising tool for entomological and molecular studies of sand flies.

PMID- 28456691
TI  - A new thioredoxin reductase with additional glutathione reductase activity in
      Haemonchus contortus.
AB  - We report, herein, the purification to homogeneity and the biochemical and
      kinetic characterization of HcTrxR3, a new isoform of thioredoxin reductase
      (TrxR) from Haemonchus contortus. HcTrxR3 was found to have a relative molecular
      weight of 134,000, while the corresponding value per subunit obtained under
      denaturing conditions, was of 67,000. By peptide mass spectrophotometric
      analysis, HcTrxR3 was determined to have 99% identity with the H. contortus
      HcTrxR1 although, and most importantly, they are different in their amino acid
      sequence in two amino acid positions: 48 (isoleucine instead of leucine) and 460
      (leucine instead of proline). The enzyme catalyzes NADPH-dependent reduction of
      DTNB and, unexpectedly, it follows the pattern of glutathione reductases (GR)
      performing the reduction of oxidized glutathione (GSSG) to reduced glutathione
      using NADPH as the reducing cofactor. Hence, it is important to highlight this
      enzyme's new and unexpected condition that makes so special and one our main
      finding. Enzyme Kcat values for DTNB, GSSG and NADPH were 12, 3 and 8 s-1,
      respectively. HcTrxR3 developed, into specific TrxR substrates: ebselen and
      sodium selenite, with activity at 0.5 and 0.068 (U/mg), respectively; and 0.044
      (U/mg) for S-nitrosoglutathione through its GR activity. The enzyme was inhibited
      by gold compound auranofin (AU), a selective inhibitor of thiol-dependent
      flavoreductases. Although HcTrxR3 has both TrxR and GR activity as thioredoxin
      glutathione reductase (TGR) does, it is a TrxR because it has no glutaredoxin
      domain and it does not develop any hysteretic behavior as does TGR. The
      importance of this new enzyme is potential to further clarify the detoxification
      and haemostasis redox mechanism in H. contortus. Likewise, this enzyme could also
      be a protein model to recognize more differences between TrxR and GR.

PMID- 28456692
TI  - Parasites as drivers of key processes in aquatic ecosystems: Facts and future
      directions.
AB  - Despite the advances in our understanding of the ecological importance of
      parasites that we have made in recent years, we are still far away from having a
      complete picture of the ecological implications connected to parasitism. In the
      present paper we highlight key issues that illustrate (1) important contributions
      of parasites to biodiversity, (2) their integral role in ecosystems, (3) as well
      as their ecological effects as keystone species (4) and in biological invasion
      processes. By using selected examples from aquatic ecosystems we want to provide
      an insight and generate interest into the topic, and want to show directions for
      future research in the field of ecological parasitology. This may help to
      convince more parasitologists and ecologists contributing and advancing our
      understanding of the complex and fascinating interplay of parasites, hosts and
      ecosystems.

PMID- 28456693
TI  - In vitro predatory activity of Arthrobotrys oligospora and after passing through
      gastrointestinal tract of small ruminants on infective larvae of
      trichostrongylides.
AB  - In vitro predatory activity of 157 native isolates of Arthrobotrys oligospora
      from China on larvae of trichostrongylides (Trichostrongylus colubriformis and
      Haemonchus contortus) in feces of sheep were assessed. The results showed that
      135 of tested isolates of A. oligospora reduced the development of
      trichostrongylide larvae in feces by 90-99.99%, 11 isolates by 80-89.46% and 11
      isolates by 14.58-78.82%. To understand their capacity of passing through
      gastrointestinal tract of sheep, 50 native isolates of A. oligospora were
      selected and assessed in sheep. Among these isolates, 16 isolates significantly
      reduced the number of larvae developing in the feces (P < 0.05); their percentage
      reduction of L3 ranged from 42.87% to 99.51% and the isolates tested were
      harvested in 5 g sub-samples of from sheep in each treatment group, indicating
      that these isolates had the capacity of preying larvae of trichostrongylides
      after the passage through gastrointestinal tract of sheep. The remaining isolates
      of A. oligospora were not able to survive after passage through gastrointestinal
      tract of sheep. In the following, the 16 isolates that presented more or less
      viability after sheep gastrointestinal passage were selected and assessed in
      goats. The results showed that the 11 isolates out of them could be able to pass
      through the digestive tract of goats without loss of ability of preying larvae of
      trichostrongylides in feces and their efficacies ranged from 53.88% to 94.28%,
      and that the isolates tested were harvested in 5 g sub-samples of feces from
      goats in each treatment group. In the current study, these isolates which
      demonstrated outstanding properties in vitro and could survive in the passage
      through the alimentary tract of sheep and goat should be potential candidates as
      a possible feed additive.

PMID- 28456694
TI  - Predictive Indices for Functional Improvement and Deterioration,
      Institutionalization, and Death Among Elderly Medicare Beneficiaries.
AB  - BACKGROUND: Prediction models can help clinicians provide the best and most
      appropriate care to their patients and can help policy makers design services for
      groups at highest risk for poor outcomes. OBJECTIVE: To develop prediction models
      identifying both risk factors and protective factors for functional
      deterioration, institutionalization, and death. DESIGN: Cohort study using data
      from the Medicare Current Beneficiary Survey (MCBS). SETTING: Community survey.
      PARTICIPANTS: This study included 21,264 Medicare beneficiaries 65 years of age
      and older who participated in the MCBS from the 2001-2008 entry panels and were
      followed up for 2 years. METHODS: The index was derived in 60% and validated in
      the remaining 40%. beta Coefficients from a multinomial logistic regression model
      were used to derive points, which were added together to create scores associated
      with the outcome. MAIN OUTCOME MEASURE: The outcome was activity of daily living
      (ADL) stage transitions over 2 years following entry into the MCBS. Beneficiaries
      were categorized into 1 of 4 outcome categories: stable or improved function,
      functional deterioration, institutionalization, or death. RESULTS: Our model
      identified 16 factors for functional deterioration (age, gender, education,
      living arrangement, dual eligibility, proxy use, Alzheimer disease/dementia,
      angina pectoris/coronary heart disease, diabetes, emphysema/asthma/chronic
      obstructive pulmonary disease, mental/psychiatric disorder, Parkinson disease,
      stroke/brain hemorrhage, hearing impairment, vision impairment, and baseline ADL
      stage) after backward selection (P < .05). Compared to stable or improved
      function, the risk of functional deterioration ranged from <=1 to >=6, <=4 to
      >=22 for the risk of institutionalization, and <=3 to >=16 for the risk of death.
      CONCLUSION: Predictive indices, or point and scoring systems used to predict
      outcomes, can identify elderly Medicare beneficiaries at risk for functional
      deterioration, institutionalization, and death and can aid policy makers,
      clinicians, and family members in improving care for older adults and supporting
      successful aging in the community. LEVEL OF EVIDENCE: III.

PMID- 28456696
TI  - A Rare Radial Artery Anatomic Variant: Look for the Pulse on the Dorsum of the
      Wrist!

PMID- 28456695
TI  - Paratubal Cyst Size Correlates With Obesity and Dysregulation of the Wnt
      Signaling Pathway.
AB  - STUDY OBJECTIVE: Paratubal cysts (PTCs) occur in 7%-10% of women, regardless of
      age. Although common, PTCs often are found incidentally because of the potential
      for these cysts to be asymptomatic. The specific aims of the study were to
      determine if PTC number and size correlated with signs of hyperandrogenism and
      obesity, as well as to investigate the molecular profiles of these PTCs in
      samples derived from female adolescents. DESIGN, SETTING, PARTICIPANTS,
      INTERVENTIONS, AND MAIN OUTCOME MEASURES: A prospective cohort study was
      performed in a single children's hospital. Girls 18 years of age or younger who
      underwent surgery for PTC suspected on the basis of the presence of a persistent
      adnexal cyst on imaging or a concern for adnexal torsion involving a cyst were
      consented to participate in the study. RESULTS: Nineteen patients met enrollment
      criteria with a mean age at menarche of 11.2 +/- 1.3 years. Most of the patients
      (84%; n = 16/19) had adnexal torsion at the time of diagnosis of PTC. Irregular
      menses and hirsutism was found in 52.6% (n = 10/19) of the patients, among whom
      36.8% (n = 7/19) were obese. The mean PTC size was 10.4 +/- 4.3 cm with 57.9% (n
      = 11/19) of the cohort having more than 1 PTC. When patients were compared on the
      basis of their body mass index, the size of PTCs was significantly larger in the
      overweight/obese group. The wingless-type (WNT) signaling members catenin beta 1
      (CTNBB1) and wingless-type MMTV integration site family, member 7A (WNT7A) were
      upregulated in 86% (n = 12/14) and 79% (n = 11/14) of the patients, respectively.
      WNT7A was significantly upregulated in girls with 1 cyst and low body mass index.
      CONCLUSION: A correlation exists between obesity, cyst size, and
      hyperandrogenism. Activation of the WNT/CTNBB1 pathway via WNT7A might play a
      role in PTC development.

PMID- 28456698
TI  - Bizarre Sequela With Cardiac Venous Perforation After Percutaneous Coronary
      Intervention.

PMID- 28456697
TI  - Impact of Plaque Rupture Detected by Optical Coherence Tomography on Transmural
      Extent of Infarction After Successful Stenting in ST-Segment Elevation Acute
      Myocardial Infarction.
AB  - OBJECTIVES: The aim of the present study was to investigate the association
      between plaque rupture (PR) assessed by optical coherence tomography (OCT), and
      the transmural extent of infarction (TEI) assessed by contrast-enhanced cardiac
      magnetic resonance imaging (CE-CMR) in ST-segment elevation myocardial infarction
      (STEMI) patients after primary percutaneous coronary intervention (PCI).
      BACKGROUND: PR is associated with larger infarct size as assessed by cardiac
      enzymes in STEMI patients. CE-CMR is a favorable method to assess TEI, which can
      predict the prognosis of STEMI patients. METHODS: First, STEMI patients with
      primary PCI within 12 h after onset were enrolled and divided into 2 groups
      according to presence (n = 71) or absence (n = 32) of PR at the culprit lesion as
      assessed by pre-intervention OCT. CE-CMR was performed at 1 week after primary
      PCI. RESULTS: The frequency of no-reflow phenomenon (37% vs. 16%; p = 0.032) and
      distal embolization (24% vs. 6%; p = 0.032) was significantly higher in the
      rupture group compared with the non-rupture group. TEI grade was significantly
      greater in the rupture group (28% vs. 15% in grade 3 and 45% vs. 13% in grade 4;
      p < 0.001). Microvascular obstruction was more frequently seen in the rupture
      group (39% vs. 19%; p = 0.039). Multivariate analysis identified PR (odds ratio:
      6.60, 95% confidence interval: 2.19 to 21.69; p < 0.001) and no statin use before
      admission (odds ratio: 3.37, 95% confidence interval: 1.06 to 11.19; p = 0.039)
      as independent predictors of TEI grade 3 or 4. CONCLUSIONS: PR as assessed by OCT
      is associated with greater TEI as assessed by CE-CMR in STEMI patients after
      primary PCI.

PMID- 28456699
TI  - Cutoff Value and Long-Term Prediction of Clinical Events by FFR Measured
      Immediately After Implantation of a Drug-Eluting Stent in Patients With Coronary
      Artery Disease: 1- to 3-Year Results From the DKCRUSH VII Registry Study.
AB  - OBJECTIVES: This study aimed to investigate the cutoff of post-drug-eluting stent
      (DES) fractional flow reserve (FFR) for prediction of 1- to 3-year target vessel
      failure (TVF). BACKGROUND: FFR immediately after a DES implantation correlates
      with clinical events. However, the cutoff of post-DES FFR for predicting long
      term clinical events remains understudied. METHODS: Between May 2012 and
      September 2013, a total of 1,476 patients who had FFR <0.8 at maximal and at
      baseline underwent DES implantation were prospectively studied in 9 centers. Post
      DES FFR was repeat measured. The primary endpoint was the 1-year TVF rate after
      procedures. Receiver-operating characteristic curves were used to calculate the
      post-DES FFR value for TVF, then patients were classified on the basis of this
      value and followed up for 3 years. RESULTS: By the end of the first year, 88
      (6.0%) TVFs were recorded. A post-DES FFR <=0.88 strongly correlated with TVF.
      Disease in the left anterior descending coronary artery (LAD), stent length, and
      stent diameter were independent factors of impaired post-DES FFR, whereas post
      procedure FFR <=0.88 was the only predictor of TVF, with 40 (4.0%) TVFs in the
      FFR >0.88 and 48 (8.0%) in the FFR <=0.88 group (p = 0.001), mainly driven by
      target vessel revascularization (3.8% vs. 8.8%; p = 0.005) and cardiac death
      (0.2% vs. 1.3%; p = 0.017). The difference in TVF between 2 groups was maintained
      through 3-year follow-up (p = 0.002). For patients with LAD lesions, a post-DES
      FFR <=0.905 predicted 1-year TVF. CONCLUSIONS: Post-DES FFR strongly correlated
      with TVF rate. Mechanisms attributed to and treatments for impaired FFR after
      stenting should be studied in future studies. (Post-DES FFR Predicts the Clinical
      Outcomes: DK CRUSH-VII, A Prospective, Multicenter, Registry Study [DK CRUSH
      VII]; ChiCTR-PRCH-12001976).

PMID- 28456700
TI  - Respect the Septal Perforator: Septal Artery Perforation During CTO PCI Resulting
      in Massive Interventricular Septal Hematoma and Biventricular Cardiac Obstructive
      Shock.

PMID- 28456701
TI  - Should Fractional Flow Reserve Be Measured After Stent Deployment? Routinely?
      Ever?

PMID- 28456702
TI  - Reconstruction of Right Coronary Artery With 2 Giant Aneurysms in Series Using 3
      Overlapped Covered Stents.

PMID- 28456703
TI  - Antimicrobial susceptibility and mechanisms of fosfomycin resistance in extended
      spectrum beta-lactamase-producing Escherichia coli strains from urinary tract
      infections in Wenzhou, China.
AB  - Fosfomycin in combination with various antibiotics represents an excellent
      clinically efficacious regimen for the treatment of urinary tract infections
      (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia
      coli. Underlying mechanisms of fosfomycin resistance remain largely
      uncharacterised. To investigate the antibacterial efficacy of fosfomycin against
      ESBL-producing E. coli, 356 non-repetitive ESBL-producing E. coli clinical
      isolates were collected from urine specimens from patients with UTI in Wenzhou,
      China, from January 2011 to December 2015. Antimicrobial sensitivity testing
      indicated that 6.7% (24/356) of the ESBL-producing E. coli strains were resistant
      to fosfomycin. The fosA3 gene encoding a fosfomycin-modifying enzyme was detected
      in 20 isolates by PCR and sequencing, alone or in combination with other ESBL
      determinants. Conjugation experiments and Southern blotting demonstrated that 70%
      (14/20) of the fosA3-positive isolates possessed transferable plasmids (ca. 54.2
      kb) co-harbouring the ESBL resistance gene blaCTX-M and the fosfomycin resistance
      gene fosA3. Among the four fosfomycin-resistant fosA3-negative E. coli isolates,
      three contained amino acid substitutions (Ile28Asn and Phe30Leu in MurA and
      Leu297Phe in GlpT). The results indicate that presence of the fosA3 gene is the
      primary mechanism of fosfomycin resistance in ESBL-producing E. coli isolates in
      Wenzhou, China. In addition, a plasmid (ca. 54.2 kb) co-harbouring fosA3 and
      blaCTX-M genes is horizontally transferable. Furthermore, a low degree of
      homology in the fosfomycin-resistant E. coli was confirmed using multilocus
      sequence typing (MLST), suggesting that there is no obvious phenomenon of clonal
      dissemination.

PMID- 28456704
TI  - Outpatient treatment of osteomyelitis with telavancin.
AB  - Telavancin is a lipoglycopeptide antibiotic with bactericidal activity against
      Gram-positive pathogens including Staphylococcus aureus, the most frequent cause
      of osteomyelitis. Treatment is often challenging due to needs for surgical
      intervention along with prolonged administration of intravenous antimicrobials,
      frequently in an outpatient setting. This was a retrospective analysis of the
      efficacy and safety of telavancin for treatment of osteomyelitis provided as
      outpatient parenteral antimicrobial therapy (OPAT) in physician office infusion
      centres. Medical records of 60 patients receiving telavancin for osteomyelitis in
      22 physician office infusion centres from 2010 to 2011 and 2013 to 2015 were
      reviewed. Of these, 60% were treated without hospitalisation, 37% had orthopaedic
      hardware and 56% had concurrent infections. Staphylococcus aureus was the most
      common pathogen (78%), primarily methicillin-resistant. The median duration of
      telavancin treatment in the outpatient setting was 21 days (range 3-105 days).
      Telavancin was used as first-line therapy in 32% of cases, following prior
      antibiotic failure in 47% and due to intolerance to previous agents in 22%,
      predominantly daptomycin or vancomycin. The telavancin dose was 10 mg/kg/day,
      adjusted for renal function in 25% of patients. The majority of patients self
      administered telavancin at home via an elastomeric infusion pump. Overall
      clinical success was 73%. No significant differences in outcomes were observed
      with the presence of hardware, concurrent infection, concomitant therapies or
      type of osteomyelitis. Telavancin-associated adverse events occurred in 57%, with
      discontinuation in three patients (5%). These data demonstrate the effective and
      safe OPAT use of telavancin, providing an alternative for successful treatment of
      patients with osteomyelitis.

PMID- 28456705
TI  - Positive epistasis of major low-cost drug resistance mutations rpoB531-TTG and
      katG315-ACC depends on the phylogenetic background of Mycobacterium tuberculosis
      strains.
AB  - Mycobacterium tuberculosis Beijing genotype strains increasingly circulate in
      different world regions, either as historical endemic, e.g. in East Asia, or
      recently imported, e.g. in South America, and this family is regarded as the most
      successful lineage of the global tuberculosis (TB) epidemic. Here we analysed the
      transmission capacity of these strains in the context of their phylogenetic
      background and drug resistance mutations. The study collection included all
      multidrug resistant (MDR) strains of Beijing genotype isolated in Beijing Chest
      Hospital, the largest tertiary TB facility in North China, in 2011-2013 (n =
      278). Strains were subjected to NTF/IS6110 and 24-loci MIRU-VNTR analysis. Drug
      resistance mutations were detected in rpoB, katG, inhA and oxyR-ahpC. A total of
      58 and 220 strains were assigned to the ancient and modern Beijing sublineages,
      respectively. 24-MIRU-VNTR clustering was higher in modern versus ancient Beijing
      strains (35.9% vs. 12.1%; P <0.001). After taking into consideration the presence
      of rpoB and katG mutations, clustering decreased to 15.9% in modern and 0% in
      ancient strains. The most frequent combination of mutations (rpoB531-TTG and
      katG315-ACC) was more prevalent in clustered versus non-clustered isolates in the
      modern sublineage (23/35 vs. 47/185; P <0.0001). To conclude, a combination of
      the known low-fitness-cost rpoB531-TTG and katG315-ACC mutations likely
      facilitates the increased transmission ability of MDR strains of the modern but
      not ancient Beijing sublineage. Accordingly, positive epistasis of major low-cost
      drug resistance-conferring mutations is influenced by the phylogenetic background
      of M. tuberculosis strains.

PMID- 28456706
TI  - Another Risk Score for Right Heart Failure: Like Having 6 Chevy Volts When All
      You Want Is a Tesla.

PMID- 28456707
TI  - Application of a narrow-surface cage in full endoscopic minimally invasive
      transforaminal lumbar interbody fusion.
AB  - BACKGROUND: Spinal endoscopy has been widely applied in lumbar discectomy and
      decompression. However, endoscopic lumbar interbody fusion still remains a
      technical challenge due to the limited space within the working trocar for cage
      implantation. The purpose of this study was to investigate the feasibility and
      effectiveness of using a narrow-surface fusion cage in full endoscopic minimally
      invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of
      lumbar degenerative disease. MATERIALS AND METHODS: From Jun 2013 to Dec 2014, a
      total of 42 patients (23 males, 19 females) underwent full endoscopic MIS-TLIF at
      our hospital was recruited. An 8-mm-wide narrow-surface fusion cage was selected
      for all cases. Perioperative parameters and complications were recorded.
      Comparisons on visual analog scale (VAS) and oswestry disability index (ODI)
      scores before and after surgery were performed. At the last follow-up, Nakai
      grading system was applied to assess patients' satisfaction; meanwhile, interbody
      fusion was evaluated by computed tomography. RESULTS: Mean operation time was
      233.1 +/- 69.5 min, and mean blood loss during surgery was 221.8 +/- 98.5 ml. Two
      patients (4.8%) developed neurological complications. Postoperative follow-up
      ranged from 24 to 36 months (mean 27.6 +/- 3.8 months). VAS and ODI scores were
      significantly improved 3 months after surgery and at the final follow-up,
      respectively (P < 0.05). Outcome of surgery was graded as excellent for 32
      patients, good for 8 patients, and acceptable for 2 patients, corresponding to a
      success rate ("good" and "excellent") of 95.2%. Thirty-nine of the 42 patients
      demonstrated solid interbody fusion at the last follow-up, indicating a fusion
      rate of 92.9%. CONCLUSION: Application of a narrow-surface fusion cage in full
      endoscopic MIS-TLIF for the treatment of lumbar degenerative disease is feasible
      and effective. The clinical outcome and fusion success of this procedure were
      acceptable and promising.

PMID- 28456708
TI  - Who requires emergency surgery for colorectal cancer and can national screening
      programmes reduce this need?
AB  - INTRODUCTION: Patients undergoing emergency colorectal cancer (CRC) surgery are
      at higher risk of poor outcome than those managed electively. The aim of this
      national study is to identify groups at high risk of undergoing unplanned CRC
      surgery and assess short and long-term outcome in this cohort subsequent
      morbidity and mortality as well as quantify their long-term survival. The aim of
      this national study is to identify groups at high risk of undergoing unplanned
      CRC surgery and assess short and long-term outcome, subsequent morbidity and
      mortality as well as quantify their long-term survival. METHODS: The Hospital
      Episode Statistics (HES) database between the years of 1997-2012 was used to
      identify all patients that had undergone surgery for colorectal cancer.
      Multivariable logistic regression analysis and cox regression analyses were
      undertaken to identify patient factors predictive of undergoing emergency and
      quantify their long-term survival. RESULTS: A total of 286,591 patients underwent
      resection for CRC between April 1997 and April 2012, of which 24.3% (69,718
      patients) were admitted as emergencies and underwent emergency surgery.
      Independent predictors of undergoing emergency surgery were female gender (OR
      1.23, CI: 1.21-1.25, p < 0.001), older age (>79 years old OR 1.55, CI: 1.50-1.60,
      p < 0.001), social deprivation (most deprived quintile, OR 1.64, CI: 1.50-1.80, p
      < 0.001) and Black African/Caribbean ethnicity (OR 1.36, CI: 1.21-1.66, p <
      0.001). All cause 30- and 90-day mortality within the emergency group was
      significantly higher than that for the electively managed patients group (13.3%
      versus compared with 3.4% at 30-days) as was 90-day (20.0% versus compared with
      5.8% at 90-days). Amongst patients eligible for bowel screening there was an
      approximate 40% significant reduction in the proportion of patients requiring
      emergency surgery before and after its introduction in 2006 (23.4%-14.9%, p <
      0.001). This reduction in emergency surgery included both proximal and distal
      cancer resections. CONCLUSION: Older, socially deprived and ethnic minority
      patients with colorectal cancer are more likely to present as emergencies
      requiring CRC surgery. Public health initiatives, such as bowel cancer screening,
      appear to have concomitantly reduced emergency and increased elective surgical
      rates within the eligible cohort. This is likely to have a beneficial impact on
      population survival. Strategies aimed at preventing emergency presentation by
      identifying patients at specific risk could improve survival outcome for
      colorectal cancer surgery in England.

PMID- 28456709
TI  - A laparoscopic approach is associated with a decreased incidence of SSI in
      patients undergoing palliative surgery for malignant bowel obstruction.
AB  - BACKGROUND: Several authors have reported on the utility of a laparoscopic
      approach for the palliation of malignant bowel obstruction (MBO); however, the
      advantages of laparoscopic surgery for MBO have not yet been confirmed. METHODS:
      We retrospectively reviewed the medical records of patients who underwent
      palliative surgery for MBO between 2007 and 2015. Laparoscopic procedures have
      been performed when technically possible since 2014. Successful palliation was
      defined as the ability to tolerate solid food (TSF) for at least 2 weeks.
      RESULTS: Twenty-two patients underwent laparoscopic palliative surgery, and 171
      patients underwent conventional open palliative surgery to relieve the symptoms
      of MBO. Laparoscopic palliative surgery was performed for patients with MBO due
      to colorectal cancer (n = 12), uterine cancer (n = 3), and other types of cancers
      (including gastric, prostate, and renal cancer). The following laparoscopic
      procedures were performed: stoma placement (n = 18), palliative resection (n = 3)
      and bypass (n = 2). The median operative time was 100 min and the median
      operative blood loss was 9 ml. The laparoscopic palliative operation allowed 91%
      (20/22) of the patients to consume a solid diet for more than 2 weeks, and be
      discharged from hospital. There were no significant differences between
      laparoscopic surgery and open surgery with regard to the ability to TSF or the
      postoperative mortality rate. The postoperative morbidity (Clavien-Dindo Grade >=
      II) rates in the laparoscopic and open surgery groups were 14% and 32%,
      respectively. Laparoscopic surgery led to a significantly lower rate of
      postoperative surgical site infection (SSI) in comparison to open surgery (4.5%
      vs 32%; P = 0.0053). CONCLUSION: A laparoscopic approach in palliative surgery
      for MBO was safe and feasible, and was associated with a lower incidence of SSIs.
      By minimizing the postoperative morbidity rate, the laparoscopic approach may
      provide significant benefits to patients with MBO who have a limited life
      expectancy.

PMID- 28456711
TI  - Paeoniflorin suppressed IL-22 via p38 MAPK pathway and exerts anti-psoriatic
      effect.
AB  - AIMS: The total glucosides of paeony (TGP) are used to treat psoriasis in the
      clinic. However, its active components and mechanisms are not clear. Paeoniflorin
      is the main constituent of TGP. Thus, the anti-psoriasis effect of paeoniflorin
      was studied, and its mechanism was explored. MATERIALS AND METHODS: The effect of
      paeoniflorin was evaluated using a psoriasis-like model of guinea pigs. The
      levels of IL-6, IL-17A, IL-22, p38 MAPK, and ERK1/2 in HaCaT cells stimulated by
      lipopolysaccharide (LPS) were determined using RT-qPCR, enzyme linked
      immunosorbent assays (ELISAs) and western blot. KEY FINDING: Compared with the
      control group, the model group showed edema, redness, and lesions in the ear upon
      stimulation with propranolol hydrochloride, and the Baker Score increased by 7
      fold. Paeoniflorin ameliorated the lesion and decreased the Baker Score by 37%
      (p<0.05). In vitro, paeoniflorin significantly inhibited the mRNA expression of
      IL-6, IL-17A and IL-22 at both 2.08 and 10.41MUM (p<0.01), and paeoniflorin had a
      marginal effect on the protein expression of IL-17A and IL-6. However, it
      inhibited the protein expression of IL-22 significantly, with inhibition ratios
      of 48.5% and 47.8% at 2.08 and 10.41MUM, respectively (p<0.05). This effect was
      achieved by inhibiting the phosphorylation of p38 MAPK. SIGNIFICANCE: The results
      of this work demonstrated that paeoniflorin is the active components of TGP and
      support its use as a therapeutic compound for psoriasis therapy.

PMID- 28456710
TI  - MicroRNA-149 is associated with clinical outcome in human neuroblastoma and
      modulates cancer cell proliferation through Rap1 independent of MYCN
      amplification.
AB  - PURPOSE: We evaluated the clinical relevance of microRNA-149 (miR-149) in
      neuroblastoma (NB) and its functional roles in regulating NB proliferation in
      vitro. METHODS: QRT-PCR was used to evaluate miR-149 expression in NB cell lines
      and primary NB tumors. Association between endogenous miR-149 expression in
      primary NB tumors and their host patients' clinicopathological factors and
      overall survival (OS) were statistically evaluated. In SH-SY5Y, an MYCN-non
      amplified, and LAN5, an MYCN-amplified NB cell lines, miR-149 was either
      upregulated or downregulated by lentiviral transduction, to evaluate its effect
      on NB proliferation in vitro. Possible downstream target of miR-149, Ras-related
      protein 1 (Rap1), was evaluated by qRT-PCR and western blot in lentiviral
      transduced NB cells. Moreover, Rap1 was either upregulated or downregulated in
      lentiviral-transduced NB cells to further evaluate its effect on miR-149-mediated
      NB proliferation in vitro. RESULTS: MiR-149 is markedly downregulated in both in
      vitro NB cell lines and in vivo NB primary tumors. Low miR-149 expression is
      predominantly associated with Stage 3 or 4 primary NB tumors, and poor OS among
      NB patients. In SH-SY5Y and LAN5 cells, lentivirus-induced miR-149 upregulation
      inhibited, whereas miR-149 downregulation promoted NB proliferation in vitro,
      despite MYCN-amplification status. Rap1 expression, at both mRNA and protein
      levels, was inversely associated with miR-149 in NB. In addition, Rap1
      upregulation or downregulation reversely regulated miR-149-mediated NB
      proliferation in vitro. CONCLUSION: MiR-149 is downregulated in NB and closely
      associated with NB patients' clinical outcome. MiR-149 also functionally
      modulates NB cell proliferation in vitro, possibly through inverse-regulation on
      Rap1.

PMID- 28456712
TI  - The FOURIER study: The profound study of Nature is the most fertile source of
      discovery.

PMID- 28456713
TI  - Breathing changes accompanying balance improvement during biofeedback.
AB  - The aim of this study was to determine whether respiration would be altered
      during visual biofeedback condition while standing on a foam surface. Fifty
      young, healthy subjects (24 men, 26 women) were divided into a spirometry group,
      in which additional spirometry analysis was performed, and a control group. All
      subjects were tested in two conditions: 1) standing on a foam surface and 2)
      standing on a foam surface with visual biofeedback (VF) based on the centre of
      pressure (CoP). CoP amplitude and velocity in anterior-posterior (Aap, Vap) and
      medial-lateral (Aml, Vml) directions were measured by the force platform.
      Breathing movements were recorded by two pairs of 3D accelerometers attached on
      the upper chest (upper chest breathing - UCB) and the lower chest (lower chest
      breathing - LCB). Results showed that significant decreases of CoP amplitude and
      velocity in both directions were accompanied by a significant decrease of lower
      chest breathing, and an increase of LCB frequency was seen during VF condition
      compared to control condition in both groups. Moreover, a significant decrease in
      tidal volume and increased breathing frequency during VF condition were confirmed
      by spirometric analysis. Reduced breathing movements and volumes as well as
      increased breathing frequency are probably part of an involuntary strategy
      activated to maximize balance improvement during VF condition.

PMID- 28456714
TI  - Energy drink enhances the behavioral effects of alcohol in adolescent mice.
AB  - Mixing alcohol with energy drinks has become increasingly popular among teenagers
      and young adults due to the prevailing view that the stimulant properties of
      energy drinks decrease the depressant effects of alcohol. Surprisingly, in spite
      of energy drinks being heavily marketed to and consumed by adolescents, there is
      scarcely available preclinical data on the neurobehavioral effects of energy
      drinks mixed with alcohol during adolescence. Thus, here we examine the effects
      of the combined exposure to alcohol and energy drink on adolescent mice using a
      variety of behavioral tasks to assess locomotor activity, righting reflex and
      motor coordination. At postnatal day 40, male and female Swiss mice were assigned
      to the following experimental groups: alcohol diluted in energy drink (Ed+Etoh),
      alcohol diluted in water (Etoh) or controls (Ctrl: energy drink or water).
      Alcohol and energy drink (Red Bull) concentrations were 4g/kg and 8ml/kg,
      respectively, and all solutions were administered via oral gavage. When compared
      to Etoh mice, Ed+Etoh animals displayed greater locomotor activity and increased
      anxiety-like behaviors in the open-field, lost their righting reflexes sooner and
      displayed poorer motor coordination in the rotarod. Collectively, our findings
      indicate that alcohol-induced deficits in adolescent mice are worsened by energy
      drink and go against the view that the stimulant properties of energy drinks can
      antagonize the adverse effects of alcohol.

PMID- 28456715
TI  - Multiple lipopolysaccharide (LPS) injections alter interleukin 6 (IL-6), IL-7, IL
      10 and IL-6 and IL-7 receptor mRNA in CNS and spleen.
AB  - Neuroinflammation is proposed to be an important component in the development of
      several central nervous system (CNS) disorders including depression, Alzheimer's
      disease, Parkinson's disease, and traumatic brain injury. However, exactly how
      neuroinflammation leads to, or contributes to, these central disorders is
      unclear. The objective of the study was to examine and compare the expression of
      mRNAs for interleukin-6 (IL-6), IL-7, IL-10 and the receptors for IL-6 (IL-6R)
      and IL-7 (IL-7R) using in situ hybridization in discrete brain regions and in the
      spleen after multiple injections of 3mg/kg lipopolysaccharide (LPS), a model of
      neuroinflammation. In the spleen, LPS significantly elevated IL-6 mRNA
      expression, then IL-10 mRNA, with no effect on IL-7 or IL-7R mRNA, while
      significantly decreasing IL-6R mRNA expression. In the CNS, LPS administration
      had the greatest effect on IL-6 and IL-6R mRNA. LPS increased IL-6 mRNA
      expression only in non-neuronal cells throughout the brain, but significantly
      elevated IL-6R mRNA in neuronal populations, where observed, except the
      cerebellum. LPS resulted in variable effects on IL-10 mRNA, and had no effect on
      IL-7 or IL-7R mRNA expression. These studies indicate that LPS-induced
      neuroinflammation has substantial but variable effects on the regional and
      cellular patterns of CNS IL-6, IL-7 and IL-10, and for IL-6R and IL-7R mRNA
      expression. It is apparent that administration of LPS can affect non-neuronal and
      neuronal cells in the brain. Further research is required to determine how CNS
      inflammatory changes associated with IL-6, IL-10 and IL-6R could in turn
      contribute to the development of CNS neurological disorders.

PMID- 28456716
TI  - Voluntary exercise increases adult hippocampal neurogenesis by increasing GSK
      3beta activity in mice.
AB  - Exercise has been proven to promote learning and memory, and is closely related
      to increased adult neurogenesis in the hippocampus. In our study, the beta
      subunit of Glycogen synthase kinase-3 (GSK3beta) can be significantly regulated
      by exercise, and the modulation of GSK3beta activity can enhance adult
      neurogenesis and memory. To explore the mechanism by which exercise can improve
      cognitive function and adult neurogenesis, and the role GSK3beta plays in this
      process, we established a mouse model of voluntary exercise to examine the
      expression and activity of GSK3beta, and its associated signaling pathways, in
      the hippocampus dentate gyrus. The results showed an obvious increase in adult
      neurogenesis and cognitive functions, and the up-regulation of GSK3beta, after
      exercise. The activity of the insulin pathway, which negatively regulates
      GSK3beta, was also increased. Moreover, our results showed that the dopamine D1
      receptor (DARP D1) pathway and adenosine 5'-monophosphate (AMP)-activated protein
      kinase (AMPK) were also activated, which indicates a relationship between
      GSK3beta and neurogenesis. Overall, our findings demonstrated that voluntary
      exercise promotes cognition and neurogenesis in the adult mouse dentate gyrus by
      the regulation of GSK3beta expression and activity, which may be implemented
      through the DARP D1 receptor-signaling pathway.

PMID- 28456717
TI  - Neuroprotective effects of low fat-protein diet in the P301L mouse model of
      tauopathy.
AB  - Tauopathies are a class of neurodegenerative diseases associated with the
      pathological aggregation of tau protein in the human brain. Although numerous
      studies in mouse models of Alzheimer disease (AD) have shown a correlation among
      diet, beta-amyloid and AD onset, little is known about the impact of diet on Tau.
      We investigated whether a low fat-protein diet (LFPD) may improve lifespan,
      cognitive and locomotor activity in P301L-tg mouse model of tauopathy. Our data
      indicate that LFPD has a beneficial effect on these parameters. Tg mice fed with
      standard diet shown a decrease in body weight, food intake and survival rate if
      compared to wild type animals. In contrast, LFPD counteracted weight loss,
      increased mortality and ameliorated cognitive and locomotor performances in tg
      mice. LFPD also reduced the abnormal accumulation of agglomerates of P-Tau
      (pathological features of tauopathies) and the expression of apoptotic markers
      (i.e., TUNEL immunopositive neurons) in the prefrontal cerebral cortex and
      hippocampus of P301L-tg mice. Interestingly, some of these effects are sex
      dependent. For instance, tg females, but not males, fed with LFPD had a
      significant increase of body weight and a reduction of P-Tau agglomerates
      compared to tg fed with standard diet. These changes correlated with a more
      pronounced improvement of cognition and locomotor activity in females than in
      male tg fed with LFPD. Altogether, these results suggest a sex dependent
      neuroprotective effect of LFPD in P301L-tg mice, suggesting that lifestyle
      intervention strategies may be clinically relevant for delaying the onset of
      cognitive impairment and dementia, especially in females.

PMID- 28456718
TI  - Role of choroid plexus in cerebrospinal fluid hydrodynamics.
AB  - The classic hypothesis presents the cerebrospinal fluid (CSF) as the "third
      circulation," which flows from the brain ventricles through the entire CSF system
      to the cortical subarachnoid space to eventually be passively absorbed into the
      superior sagittal sinus through arachnoid granulations. The choroid plexus (CP)
      represents a key organ in the classic CSF physiology and a powerful biological
      pump, which exclusively secretes CSF. Thereby, the CP is considered to be
      responsible for CSF pressure regulation and hydrocephalus development. This
      article thoroughly analyzes the role of the CP in the CSF dynamics, presenting
      arguments in favor of the thesis that the CPs are neither biological pumps nor
      the main site of CSF secretion; that they do not participate in regulation of
      ICP/CSF pressure; are not the reason for the existence of hydrostatic pressure
      gradient in the CSF system and that this gradient is not permanent (disappeared
      in the horizontal position); and that they do not generate imagined
      unidirectional CSF circulation, hydrocephalus development and increased ICP/CSF
      pressure. The classic hypothesis cannot provide an explanation for these
      controversies but the recently formulated Bulat-Klarica-Oreskovic hypothesis can.
      According to this hypothesis, CSF production and absorption (CSF exchange) are
      constant and present everywhere in the CSF system, and although the CSF is
      partially produced by the CP, it is mainly formed as a consequence of water
      filtration between the capillaries and interstitial fluid.

PMID- 28456719
TI  - Abnormalities in CD57+ cytotoxic T cells and Vdelta1+ gammadeltaT cells in
      subclinical celiac disease in childhood are affected by cytomegalovirus. The
      Generation R Study.
AB  - Celiac disease (CD) is a digestive and autoimmune disorder driven by an immune
      response to modified gluten peptides. Affected intestines show infiltrates of
      various T-cell and NK-cell subsets. It is currently unclear if individuals with
      subclinical CD have systemic abnormalities in immune cells. We here studied
      whether subclinical CD is associated with changes in blood CD57-expressing and
      Vdelta1-expressing lymphocytes in children, and whether cytomegalovirus (CMV)
      infection modifies this association. Included were 1068 children from the
      Generation R Study. Serum Immunoglobulin G (IgG) levels against CMV were measured
      by ELISA; Tissue transglutaminase type 2 antibody (TG2A) levels with fluorescence
      enzyme immunoassay (FEIA). Duodenal biopsies, additional Human Leukocyte Antigen
      (HLA) DQ 2.2, 2.5 and 8 and endomysial antibody (EMA) typing were performed in
      TG2A positive children. Subclinical CD cases (n=12) had 1.8 fold (95% CI 1.06;
      3.1) fewer Vdelta1+ T cells which was predominantly observed in CMV seronegative
      children (p-interaction 0.02), and 2.7 fold (95% CI 1.25; 5.99) more CD57+ T
      cells than HLA DQ2/-DQ8 positive controls (n=339). Hence, children with
      subclinical CD have alterations in specific blood T cell subsets that are linked
      to viral pathology. The observed interaction effect between subclinical CD and
      CMV may contribute to the understanding of disease pathogenesis.

PMID- 28456720
TI  - Regulation of Tight-Junction Integrity by Insulin in an In Vitro Model of Human
      Blood-Brain Barrier.
AB  - Although insulin receptor is expressed at the human blood-brain barrier (BBB),
      the physiological and pathologic roles of insulin signaling in biologic responses
      at the BBB remain unclear. Here, we investigate insulin signaling at the human
      BBB using human cerebral microvascular endothelial cell line (hCMEC/D3) as a well
      established in vitro model. Western blot analysis showed that insulin induced
      phosphorylation of extracellular signal-regulated kinase and insulin receptor
      substrate-1 in hCMEC/D3 cells. Short-term insulin stimulation increased cell
      proliferation via the canonical phosphoinositide-3 kinase/protein kinase B and
      mitogen-activated protein kinase signaling pathways, suggesting that insulin
      signaling is involved in the regulation of biologic responses in the human BBB.
      We also found that insulin rapidly increased tight-junction integrity of hCMEC/D3
      cells via the phosphoinositide-3 kinase/protein kinase B/glycogen synthase kinase
      3 beta signaling pathway. Inhibition of insulin/insulin-like growth factor-1
      receptor kinase by AG1024 blocked the increase of tight-junction integrity. In
      addition, high-insulin/high-glucose treatment (as a model of hyperglycemia and
      hyperinsulinemia) synergistically reduced the tight-junction integrity in
      hCMEC/D3 cells, although either condition alone had little or no effect. Our
      findings suggest that, in addition to the established role of interactions of
      astrocytes and pericytes with brain capillary endothelial cells, insulin
      signaling from the blood side of the BBB contributes to maintenance of
      homeostasis by regulating cell proliferation and tight-junction integrity.

PMID- 28456721
TI  - Investigation of the Importance of Multidrug Resistance-Associated Protein 4
      (Mrp4/Abcc4) in the Active Efflux of Anionic Drugs Across the Blood-Brain
      Barrier.
AB  - The importance of multidrug resistance-associated protein 4 (Mrp4/Abcc4) in
      limiting the penetration of Mrp4 substrate compounds into the central nervous
      system across the blood-brain barrier was investigated using Mrp4-/- mice.
      Significant adenosine triphosphate-dependent uptake by MRP4 was observed for
      ochratoxin A, pitavastatin, raltitrexed (Km = 43.7 MUM), pravastatin, cyclic
      guanosine monophosphate, 2,4-dichlorophenoxyacetate, and urate. The defect in the
      Mrp4 gene did not affect the brain-to-plasma ratio (Kp,brain) of quinidine and
      dantrolene. Following intravenous infusion in wild-type and Mrp4-/- mice, the
      plasma concentrations of the tested compounds (cefazolin, cefmetazole,
      ciprofloxacin, cyclophosphamide, furosemide, hydrochlorothiazide, methotrexate,
      pitavastatin, pravastatin, and raltitrexed) were identical; however, Mrp4-/- mice
      showed a significantly higher (1.9- to 2.5-fold) Kp,brain than wild-type mice for
      methotrexate, raltitrexed, and cyclophosphamide. GF120918, a dual inhibitor of P
      gp and Bcrp, significantly decreased Kp,cortex and Kp,cerebellum only in Mrp4-/-
      mice. Methotrexate and raltitrexed are also substrates of multispecific organic
      anion transporters such as Oatp1a4 and Oat3. GF120918 showed an inhibition
      potency against Oatp1a4, but not against Oat3. These results suggest that Mrp4
      limits the penetration of methotrexate and raltitrexed into the brain across the
      blood-brain barrier, which is likely to be facilitated by some uptake
      transporters.

PMID- 28456722
TI  - The Delivery of Small Interfering RNA to Hepatic Stellate Cells Using a Lipid
      Nanoparticle Composed of a Vitamin A-Scaffold Lipid-Like Material.
AB  - Hepatic stellate cells (HSCs) are responsible for hepatic fibrosis and liver
      cirrhosis via their ability to produce extracellular matrices such as collagens
      and elastin. However, a strategy for delivering cargoes to HSCs has not been
      established yet. We herein report on attempts to deliver small interfering RNA
      (siRNA) to HSCs using several types of SS-cleavable proton-activated lipid-like
      materials (ssPalms) that contained myristic acid (ssPalmM) or hydrophobic vitamin
      A (ssPalmA) and E (ssPalmE) as hydrophobic scaffolds. We initially verified that
      hepatic fibrosis could induce the treatment with tetrachloromethane in terms of
      collagen fibrils and the expression of marker genes, type I collagen alpha-1,
      transforming growth factor beta, heat shock protein 47, and alpha-smooth muscle
      actin. The siRNA silencing efficiency of the 3 LNPs was then compared using
      fibrosis-induced mice. Of the materials tested, LNPssPalmA showed the highest
      efficiency, with an effective (ED)50 of approximately 0.25 mg siRNA/kg. The
      LNPssPalmA showed a significant inhibitory effect on collagen production at a
      dose of 3.0 mg siRNA/kg with no evidence of any severe adverse effects. In
      conclusion, LNPssPalmA holds considerable potential for use in the treatment of
      HSCs-mediated diseases.

PMID- 28456723
TI  - Hepatobiliary Clearance Prediction: Species Scaling From Monkey, Dog, and Rat,
      and In Vitro-In Vivo Extrapolation of Sandwich-Cultured Human Hepatocytes Using
      17 Drugs.
AB  - Hepatobiliary elimination can be a major clearance pathway dictating the
      pharmacokinetics of drugs. Here, we first compared the dose eliminated in bile in
      preclinical species (monkey, dog, and rat) with that in human and further
      evaluated single-species scaling (SSS) to predict human hepatobiliary clearance.
      Six compounds dosed in bile duct-cannulated (BDC) monkeys showed biliary
      excretion comparable to human; and the SSS of hepatobiliary clearance with plasma
      fraction unbound correction yielded reasonable predictions (within 3-fold).
      Although dog SSS also showed reasonable predictions, rat overpredicted
      hepatobiliary clearance for 13 of 24 compounds. Second, we evaluated the
      translatability of in vitro sandwich-cultured human hepatocytes (SCHHs) to
      predict human hepatobiliary clearance for 17 drugs. For drugs with no significant
      active uptake in SCHH studies (i.e., with or without rifamycin SV), measured
      intrinsic biliary clearance was directly scalable with good predictability
      (absolute average fold error [AAFE] = 1.6). Drugs showing significant active
      uptake in SCHH, however, showed improved predictability when scaled based on
      extended clearance term (AAFE = 2.0), which incorporated sinusoidal uptake along
      with a global scaling factor for active uptake and the canalicular efflux
      clearance. In conclusion, SCHH is a useful tool to predict human hepatobiliary
      clearance, whereas BDC monkey model may provide further confidence in the
      prospective predictions.

PMID- 28456724
TI  - Characterization of Protein Particles in Therapeutic Formulations Using Imaging
      Flow Cytometry.
AB  - Quantitation of particles >10 MUm in therapeutic protein formulations is required
      by pharmacopeia guidelines, and characterization of particles <10 MUm is
      increasingly expected. Established methods offer limited ability to detect or
      characterize small particles; consequently, new methods are needed to measure the
      sub-10 MUm size range. Here, we evaluate imaging flow cytometry (IFC) as a new
      method for detection of protein aggregates, taking advantage of key enabling
      attributes including rapid multi-modal high-resolution imaging of individual
      particles, low sample volume, high sampling efficiency, wide dynamic size and
      concentration range, and low clog risk. IFC sensitivity was compared with dynamic
      imaging, a "gold standard" technique for analysis of particles in protein
      formulations. Both techniques yielded similar results for polystyrene beads >=2
      MUm. However, IFC demonstrated greater protein particle detection sensitivity,
      especially for the sub-10 MUm size range. Interestingly, for an aggregated
      lysozyme sample, IFC detected protein particles using fluorescence images,
      whereas dynamic imaging failed to detect even large particles >25 MUm due to high
      transparency. The results corroborate implementation of IFC as an advanced
      technique for protein particle analysis, offering in-depth characterization of
      particle physical and chemical properties, and enhanced sensitivity for sub-10
      MUm and transparent particles.

PMID- 28456725
TI  - Is Failure of Cocrystallization Actually a Failure? Eutectic Formation in
      Cocrystal Screening of Hesperetin.
AB  - Cocrystal screening of hesperetin with certain countermolecules generated highly
      soluble noncovalent derivatives in the form of eutectics, instead of expected
      cocrystals. As adhesive forces established by complimentary functional groups on
      hesperetin and coformers were unable to overcome the stress due to size shape
      mismatch of component molecules, thus, eutectics were formed. Hesperetin, a
      polyphenolic antioxidant with potent anticancer and cardioprotective effects, has
      an underdeveloped role in modern therapeutics on account of its critically low
      aqueous solubility resulting in stunted bioavailability. The liquid-assisted
      cogrinding of hesperetin and coformers generated binary-phase eutectics in fixed
      stoichiometry with theophylline (1:1.5), adenine (2:1), gallic acid (1.5:1), and
      theobromine (2:1). Primarily characterized by lower melting endotherm in
      differential scanning calorimetry, the eutectics showed complete melting in hot
      stage microscopy. Apart from characteristic V-shaped binary-phase diagram, no
      discernible changes in the FTIR and powder X-ray diffraction spectra further
      confirm eutectic formation. The morphological differences were analyzed by SEM
      measurements. A 2 to 4 times enhanced dissolution profile of the eutectics
      measured in pH 7.4 aqueous buffer was coupled with the in vitro (1,1-diphenyl-2
      picryl hydroxyl free radical antioxidant assay and RBC antihemolytic assay)
      studies to present a complete preliminary data on the improved bioavailability of
      hesperetin eutectics.

PMID- 28456727
TI  - Species Differences in the Binding of Sodium 4-Phenylbutyrate to Serum Albumin.
AB  - Sodium 4-phenylbutyrate (PB) is clinically used as a drug for treating urea cycle
      disorders. Recent research has shown that PB also has other pharmacologic
      activities, suggesting that it has the potential for use as a drug for treating
      other disorders. In the process of drug development, preclinical testing using
      experimental animals is necessary to verify the efficacy and safety of PB.
      Although the binding of PB to human albumin has been studied, our knowledge of
      its binding to albumin from the other animal species is extremely limited. To
      address this issue, we characterized the binding of PB to albumin from several
      species (human, bovine, rabbit, and rat). The results indicated that PB interacts
      with 1 high-affinity site of albumin from these species, which corresponds to
      site II of human albumin. The affinities of PB to human and bovine albumins were
      higher than those to rabbit and rat albumin, and that to rabbit albumin was the
      lowest. Binding and molecular docking studies using structurally related
      compounds of PB suggested that species differences in the affinity are attributed
      to differences in the structural feature of the PB-binding sites on albumins
      (e.g., charge distribution, hydrophobicity, shape, or size).

PMID- 28456726
TI  - Optimization of the Production Process and Characterization of the Yeast
      Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1), a SARS
      Vaccine Candidate.
AB  - From 2002 to 2003, a global pandemic of severe acute respiratory syndrome (SARS)
      spread to 5 continents and caused 8000 respiratory infections and 800 deaths. To
      ameliorate the effects of future outbreaks as well as to prepare for biodefense,
      a process for the production of a recombinant protein vaccine candidate is under
      development. Previously, we reported the 5 L scale expression and purification of
      a promising recombinant SARS vaccine candidate, RBD219-N1, the 218-amino acid
      residue receptor-binding domain (RBD) of SARS coronavirus expressed in yeast
      Pichia pastoris X-33. When adjuvanted with aluminum hydroxide, this protein
      elicited high neutralizing antibody titers and high RBD-specific antibody titers.
      However, the yield of RBD219-N1 (60 mg RBD219-N1 per liter of fermentation
      supernatant; 60 mg/L FS) still required improvement to reach our target of >100
      mg/L FS. In this study, we optimized the 10 L scale production process and
      increased the fermentation yield 6- to 7-fold to 400 mg/L FS with purification
      recovery >50%. A panel of characterization tests indicated that the process is
      reproducible and that the purified, tag-free RBD219-N1 protein has high purity
      and a well-defined structure and is therefore a suitable candidate for production
      under current Good Manufacturing Practice and future phase-1 clinical trials.

PMID- 28456728
TI  - Paclitaxel-Loaded Magnetic Nanoparticles: Synthesis, Characterization, and
      Application in Targeting.
AB  - Iron oxide magnetic nanoparticles (MNPs) are good candidates to implement fluid
      therapy in critical patients in clinic integrated system. Herein, we synthesized
      paclitaxel (PTX)-loaded MNPs modified with methoxy polyethylene glycol (PEG)
      lysine-oleic acid2 (PTX-MNPs-PLO), which is expected to act as a magnetic
      resonance imaging (MRI) contrast agent and meanwhile for cancer therapy. MNPs
      were synthesized by thermal decomposition. Dialysis method was applied to prepare
      PTX-MNPs-PLO with 3 different PEG molecular weights (1000, 2000, and 4000 Da),
      which were subsequently freeze-dried into powders. PTX-MNPs-PLO was characterized
      by transmission electron microscope, scanning electron microscope,
      thermogravimetric analysis, vibrating sample magnetometer, and MRI. What is more
      is that pharmacokinetics and distribution in vivo were processed, the results of
      which exhibited that PTX-MNPs-PLO2000 had the longer circulation lifetime
      compared with Taxol, PTX-MNPs-PLO1000, and PTX-MNPs-PLO4000. Results of magnetic
      targeting in kidneys suggested that deep buried or ultrasmall magnet is likely to
      be more preferable. PTX-MNPs-PLO2000 holds great promise in the application of
      magnetic accumulation, target drug delivery, and thermal therapy.

PMID- 28456729
TI  - In Vitro-In Vivo Extrapolation of Metabolism- and Transporter-Mediated Drug-Drug
      Interactions-Overview of Basic Prediction Methods.
AB  - Evaluation of drug-drug interaction (DDI) risk is vital to establish benefit-risk
      profiles of investigational new drugs during drug development. In vitro
      experiments are routinely conducted as an important first step to assess
      metabolism- and transporter-mediated DDI potential of investigational new drugs.
      Results from these experiments are interpreted, often with the aid of in vitro-in
      vivo extrapolation methods, to determine whether and how DDI should be evaluated
      clinically to provide the basis for proper DDI management strategies, including
      dosing recommendations, alternative therapies, or contraindications under various
      DDI scenarios and in different patient population. This article provides an
      overview of currently available in vitro experimental systems and basic in vitro
      in vivo extrapolation methodologies for metabolism- and transporter-mediated
      DDIs.

PMID- 28456730
TI  - Usefulness of PBPK Modeling in Incorporation of Clinical Conditions in
      Personalized Medicine.
AB  - Personalized medicine aims to determine the most adequate treatment and dose
      regimen to obtain the maximum efficacy and minimum side effect by taking into
      account patients' characteristics. For numerous reasons, one being ethical and
      methodological hurdles in including specific populations in clinical trials,
      innovative methods for optimization of drugs safety and efficacy in such patients
      have received increasing interest recently. Physiological-based pharmacokinetic
      (PBPK) modeling has emerged as a promising approach in designing adequate
      clinical trials and quantifying anticipated changes in unknown clinical
      situations. In this review, current state of knowledge on the usefulness of PBPK
      modeling in estimation of drug exposure in specific medical conditions including
      pregnancy, pediatrics, elderly, patients with liver or renal impairment, obesity,
      and following bariatric surgery were outlined. Modulations of key system
      parameters occurring in these patient populations were illustrated. Furthermore,
      the application of PBPK approach in dose recommendations and quantification of
      drug exposure in carriers of genetic polymorphisms was summarized. Despite the
      uncertainties and knowledge gaps related to parameters influencing drugs
      bioavailability in each clinical condition, PBPK models provide a valuable
      support for prospective dose recommendations and efficacy/safety assessment in
      special populations when consistent clinical data are lacking.

PMID- 28456732
TI  - Packing Polymorphism of Dapivirine and Its Impact on the Performance of a
      Dapivirine-Releasing Silicone Elastomer Vaginal Ring.
AB  - A silicone elastomer vaginal ring providing sustained release over 28 days of the
      anti-retroviral microbicide dapivirine has recently completed phase III clinical
      testing and showed moderate protection against HIV acquisition. In support of the
      product licensure program, we report the impact of dapivirine packing
      polymorphism on the thermal and solubility characteristics of dapivirine and on
      the in vitro performance of the 25 mg dapivirine ring product. This is the first
      time that polymorphism has been reported for a drug-releasing vaginal ring
      product. Thermal, particle size, powder X-ray diffraction, and thermodynamic
      solubility analyses of dapivirine polymorphic forms I and IV, both of which are
      persistent at room temperature and with form I being the thermodynamically stable
      form, were conducted for both micronized and non-micronized materials. No
      significant differences in solubility between DPV forms I and IV were observed in
      media commonly used for in vitro release testing. Matrix-type silicone elastomer
      vaginal rings were manufactured and the impact of dapivirine polymorphism on key
      in vitro parameters (compression and tensile behavior; content assay; in vitro
      release; residual content assay) was investigated. The data demonstrate that
      dapivirine packing polymorphism has no significant impact on in vitro performance
      of the 25 mg dapivirine vaginal ring.

PMID- 28456733
TI  - Utility of High Throughput Screening Techniques to Predict Stability of
      Monoclonal Antibody Formulations During Early Stage Development.
AB  - Selecting optimal formulation conditions for monoclonal antibodies for first time
      in human clinical trials is challenging due to short timelines and reliance on
      predictive assays to ensure product quality and adequate long-term stability.
      Accelerated stability studies are considered to be the gold standard for
      excipient screening, but they are relatively low throughput and time consuming.
      High throughput screening (HTS) techniques allow for large amounts of data to be
      collected quickly and easily, and can be used to screen solution conditions for
      early formulation development. The utility of using accelerated stability
      compared to HTS techniques (differential scanning light scattering and
      differential scanning fluorescence) for early formulation screening was evaluated
      along with the impact of excipients of various types on aggregation of monoclonal
      antibodies from multiple IgG subtypes. The excipient rank order using
      quantitative HTS measures was found to correlate with accelerated stability
      aggregation rate ranking for only 33% (by differential scanning fluorescence) to
      42% (by differential scanning light scattering) of the antibodies tested, due to
      the high intrinsic stability and minimal impact of excipients on aggregation
      rates and HTS data. Also explored was a case study of employing a platform
      formulation instead of broader formulation screening for early formulation
      development.

PMID- 28456731
TI  - Different Involvement of OAT in Renal Disposition of Oral Anticoagulants
      Rivaroxaban, Dabigatran, and Apixaban.
AB  - This study aimed to investigate the interactions of 3 anticoagulants,
      rivaroxaban, apixaban, and dabigatran, with 5 human solute carrier transporters,
      hOAT1, hOAT3, hOCT2, hOATP1B1, and hOATP1B3. Apixaban inhibited hOAT3, hOATP1B1,
      and hOATP1B3, and rivaroxaban inhibited hOAT3 and hOATP1B3, with IC50 values of
      >20 and >5 MUM, respectively. The effect of dabigatran was negligible or very
      weak, so significant drug interactions at therapeutic doses are unlikely.
      Specific uptake of rivaroxaban was observed only in human and mouse OAT3
      expressing cells. The Km for mouse Oat3 (mOat3) was 1.01 +/- 0.70 MUM. A defect
      in mOat3 reduced the kidney-to-plasma concentration ratio of rivaroxaban by 38%
      in mice. Probenecid treatment also reduced the kidney-to-plasma concentration
      ratio of rivaroxaban in rats by 73%. Neither mOat3 defect nor probenecid
      administration in rats reduced the renal clearance of rivaroxaban. The uptake of
      rivaroxaban by monkey kidney slices was temperature dependent and inhibited by
      probenecid but not by tetraethylammonium. Taken together, organic anion
      transporters, mainly OAT3, may mediate basolateral uptake of rivaroxaban in
      kidneys. hOAT3 could be an additional factor that differentiates the potential
      drug-drug interactions of the 3 anticoagulants in the urinary excretion process
      in clinical settings.

PMID- 28456734
TI  - Thermosensitive Gel-Based Formulation for Intratumoral Delivery of Toll-Like
      Receptor 7/8 Dual Agonist, MEDI9197.
AB  - Toll-like receptor (TLR) agonists TLR 7/8, MEDI9197, is a imidazoquinoline
      analogue that can be used for cancer immunotherapy based on its efficacy toward a
      variety of tumors. Systemic administration of TLR agonists results in stimulation
      of the immune system throughout the entire body causing undesirable side effects.
      To minimize these adverse events, local administration of TLR agonists including
      intratumoral (IT) delivery has been introduced. Here, a poloxamer 407 thermogel
      formulation for IT delivery of a TLR 7/8 dual agonist, MEDI9197, is described in
      which the combination of the aqueous thermogel and the ethanolic TLR 7/8 dual
      agonist, MEDI9197, solution leads to precipitated drug particles within the gel.
      The in vitro release profile showed an initial burst followed by sustained
      release. A B16-OVA mouse tumor model was used to assess the in vivo
      pharmacokinetics, efficacy, and systemic cytokine and chemokine (cytokine)
      production of the poloxamer 407-based thermogel formulation. The pharmacokinetic
      evaluation showed that the agonist level within the tumor was reduced by ~70%
      over 14 days while serum agonist levels indicated an initial burst at the 6-h
      time point followed by a drop in serum drug levels over the 14 days of the
      experiment. The tumor growth inhibition, survival, and serum cytokines for post
      IT injection of the poloxamer 407 formulation showed that it slowly released TLR
      7/8 agonist, MEDI9197, resulting in more efficacious tumor growth inhibition
      compared with control groups. In addition, the cytokine levels in circulation
      indicated that a dose increase led to a decrease in the serum inflammatory and
      interferon-inducible cytokines levels. This observation could be due to a
      reduction of drug diffusion and escape from the tumor site due to the
      precipitation of the drug inside the tumor leading to sustained release. IT
      delivery of TLR 7/8 dual agonist, MEDI9197, via a thermosensitive gel-based
      formulation was efficacious and could offer an alternate method of local drug
      delivery.

PMID- 28456735
TI  - Aneurysms of the Proximal Segment of the Anterior Cerebral Artery: A New
      Classification System with Corresponding Therapeutic Options.
AB  - OBJECTIVE: This study aims to establish a new classification system for proximal
      anterior cerebral artery (A1) aneurysms and to offer treatment strategies, based
      on the lessons learned by studying the case reports of 41 patients with A1
      aneurysms. METHODS: A total of 2332 consecutive patients with intracranial
      aneurysms were treated at a single medical center between June 2005 and May 2015.
      Forty-one patients with 42 A1 aneurysms were treated by surgical clipping or
      endovascular coiling. Clinical data, radiographic results, treatments, and
      patient outcomes were later collected and analyzed. RESULTS: Of 2332 intracranial
      aneurysm patients, 1.76% (n = 41) had a total of 42 A1 aneurysms. Twenty-six of
      these (62%) were proximal A1 segment aneurysms, 9 (21%) were distal A1 segment
      aneurysms, and 7 (17%) were fusiform A1 aneurysms. A1 aneurysms can be classified
      into 3 main types. Types IA and IB originate from the posterior wall of the
      proximal A1 segment. Type IA projects posterior-inferiorly, whereas type IB
      projects posterior-superiorly. Type IIA originates from the distal trunk of the
      A1 artery. Type IIB originates from an angle of an abnormal cortical branch or a
      ring of an A1 arterial fenestration. Type III consists of fusiform or dissecting
      aneurysms located anywhere along the A1 segment. After studying the range of
      treatments and outcomes, when treating these complex morphologies, we recommend
      clipping type I and II A1 aneurysms and embolizing type III A1 aneurysms.
      CONCLUSIONS: A1 artery aneurysms are a rare type of aneurysm with unique
      characteristics. The classification system proposed here accurately summarizes
      these characteristics to better guide treatment strategies.

PMID- 28456736
TI  - Endoscope-Assisted Extreme-Lateral Interbody Fusion: Preliminary Experience and
      Technical Note.
AB  - BACKGROUND: The extreme lateral lumbar interbody fusion (XLIF) technique is safe
      and effective; however, the deep and tight surgical corridor makes visual
      identification of important landmark structures, as well as sufficient endplate
      and contralateral preparation, challenging. In the present study, we analyzed the
      safety and feasibility of endoscope-assisted (EA) XLIF procedures. METHODS: This
      was a retrospective single-center study on consecutive patients undergoing XLIF
      procedures between February 2014 and July 2016. EA-XLIF and conventional XLIF (c
      XLIF) procedures were compared in terms of the duration of surgery, estimated
      blood loss (EBL), perioperative and postoperative complications, and
      postoperative outcomes. RESULTS: A total of 41 patients (mean age, 66.7 years +/-
      10.0 years; 22 males [53.7%]) underwent a XLIF procedure, including 6 (14.6%) who
      underwent EA-XLIF. EA-XLIF did not increase the duration of surgery or EBL. No
      perioperative or postoperative complications were observed in any of the EA-XLIF
      procedures. Clinical and radiologic outcomes at 6 weeks postsurgery and at the
      last follow-up (mean, 8.0 +/- 5.8 months postsurgery) were similar for patients
      in the EA-XLIF and c-XLIF groups. The EA-XLIF technique was considered
      particularly helpful for checking the lumbar plexus anatomy on the psoas surface,
      identifying the relationship between the peritoneum and the psoas muscle,
      positioning the shim into the disc space, removing the disk, and checking the
      quality of contralateral release and endplate preparation. CONCLUSIONS: The EA
      XLIF technique is safe and may be considered as an adjunct procedure, offering
      improved visualization to guide the surgeon in key steps of the XLIF procedure.

PMID- 28456737
TI  - Surgeon Adherence to Medical Ethics as Contingent on Their Leadership in the
      Changing Economics of Health Care.

PMID- 28456738
TI  - Commerce Versus Science: A Perpetual Dialectic.

PMID- 28456739
TI  - Complications and Readmission After Cervical Spine Surgery in Elderly Patients:
      An Analysis of 1786 Patients.
AB  - OBJECTIVE: To investigate risk factors and complications of cervical spine
      surgery in elderly patients. METHODS: A retrospective study was performed using
      data from the American College of Surgeons National Surgical Quality Improvement
      Program. Patients >=65 years old who underwent cervical spine surgery from 2005
      to 2013 were identified using International Classification of Diseases, Ninth
      Revision, Clinical Modification diagnosis and Current Procedural Terminology
      codes. Outcome data were classified as major complication, minor complication,
      readmission, or mortality. RESULTS: Of 1786 patients >=65 years old undergoing
      cervical spine surgery identified, 175 (9.80%) patients experienced at least 1
      complication or death. Patients >=75 years old were at higher risk of developing
      a complication or death (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.13
      2.61). Patients with increased operative times (OR 3.54, 95% CI 2.27-5.53),
      patients who were partially or totally dependent (OR 3.01, 95% CI 1.79-5.07), and
      patients listed as American Society of Anesthesiologists class III/IV/V (OR 1.87,
      95% CI 1.20-2.94) had increased risks of perioperative complications. Patients 70
      74 years old (OR 1.94, 95% CI 1.03-3.65) and patients with at least 1
      postoperative complication (OR 9.59, 95% CI 5.17-17.80) had increased risks of
      unplanned readmissions. Patients >=75 years old undergoing a
      laminectomy/laminotomy were at higher risk of complications (OR 3.20, 95% CI 1.33
      7.70), whereas there was no difference in risk of complications based on age for
      elderly patients undergoing a fusion. CONCLUSIONS: Patient comorbidities and
      clinical factors, such as longer operating time and emergency cases, impact risk
      of adverse events. Patients 70-74 years old and patients with at least 1
      postoperative complication had an increased risk of unplanned readmission.

PMID- 28456740
TI  - A New Determinant of Poor Outcome After Spontaneous Subarachnoid Hemorrhage:
      Blood pH and the Disruption of Glossopharyngeal Nerve-Carotid Body Network: First
      Experimental Study.
AB  - OBJECTIVE: The chemoreceptor network, consisting of the glossopharyngeal nerve
      and carotid body (GPN-CB), is essential for the regulation of blood pH. Its
      ischemic insults after subarachnoid hemorrhage (SAH), which may contribute to
      acidosis, have not been investigated. METHODS: Twenty-three hybrid rabbits were
      used. They were divided into 3 groups: 5 as a control group, 5 as a sham group,
      and the remaining 13 as the study group. Injections included 1 cm3 serum saline
      and 1 cm3 autolog arterial blood into the cisterna magna in the sham and study
      group, respectively. Blood pH values of all animals were recorded. After 2 weeks,
      animals were euthanized. The number of normal and degenerated neurons of the
      carotid bodies (CBs) was counted by stereologic methods and analyzed
      statistically. RESULTS: Two of 13 rabbits died within the second week. The mean
      blood pH values were measured as 7.35 +/- 0.07 in the control group (n = 5), 7.33
      +/- 0.06 in the sham group (n = 5), 7.29 +/- 0.05 in rabbits with slight acidosis
      (n = 6), and 7.23 +/- 0.02 in rabbits with prominent acidosis (n = 7). In the
      control group, the average normal neuronal density of the CBs was 6432 +/-
      790/mm3 and the degenerated neuron density was 11 +/- 3/mm3, whereas the
      degenerated neuronal density in CBs was 35 +/- 8/mm3 in the sham group and 1034
      +/- 112/mm3 in the slight acidosis-developed group (n = 6; P < 0.05). Conversely,
      degenerated neuron density of CBs was 2134 +/- 251/mm3 in the prominent acidosis
      developed animals (n = 7; P < 0.005). Interestingly, in the rabbits who died, the
      degenerated neuron density of the CB was 3160 +/- 840/mm3. CONCLUSION: An inverse
      relationship between neurodegeneration in the CB and pH values secondary to the
      disruption of the GPN-CB network after SAH was found, which may contribute to
      developing acidosis.

PMID- 28456741
TI  - Endoscopic Transseptal Transcaval Interforniceal Approach to the Posterior Third
      Ventricle in the Presence of Cavum Septum Pellucidum.
AB  - BACKGROUND: Posterior third ventricular lesions often cause obstructive
      hydrocephalus. Thus, a combined endoscopic third ventriculostomy (ETV) and
      endoscopy biopsy are often the first treatment. However, the trajectories for
      both procedures can differ significantly, necessitating 2 entry points or a
      combined rigid-flexible technique. METHODS: We describe the use of a large cavum
      septum pellucidum as a route for performing the biopsy. RESULTS: Using a rigid
      endoscope and a single trajectory, we were able to perform a transforaminal ETV
      and a transseptal, transcaval, interforniceal biopsy of the tumor. CONCLUSION:
      Although described as a route to reach the anterior third ventricle
      endoscopically, we describe the use of the transseptal, transcaval,
      interforniceal approach to reach the posterior part of the third ventricle.

PMID- 28456742
TI  - Quantitative Computed Tomography Ventriculography for Assessment and Monitoring
      of Hydrocephalus: A Pilot Study and Description of Method in Subarachnoid
      Hemorrhage.
AB  - BACKGROUND: There is no facile quantitative method for monitoring hydrocephalus
      (HCP). We propose quantitative computed tomography (CT) ventriculography (qCTV)
      as a novel computer vision tool for empirically assessing HCP in patients with
      subarachnoid hemorrhage (SAH). METHODS: Twenty patients with SAH who were
      evaluated for ventriculoperitoneal shunt (VPS) placement were selected for
      inclusion. Ten patients with normal head computed tomography (CTH) findings were
      analyzed as negative controls. CTH scans were segmented both manually and
      automatically (by qCTV) to generate measures of ventricular volume. RESULTS: The
      median manually calculated ventricular volume was 36.1 cm3 (interquartile range
      [IQR], 30-115 cm3), which was similar to the median qCTV measured volume of 37.5
      cm3 (IQR, 32-118 cm3) (P = 0.796). Patients undergoing VPS placement demonstrated
      an increase in median ventricular volume on qCTV from 21 cm3 to 40 cm3 on day T-2
      and to 51 cm3 by day 0, a change of 144%. This is in contrast to patients who did
      not require shunting, in whom median ventricular volume decreased from 16 cm3 to
      14 cm3 on day T-2 and to 13 cm3 by day 0, with an average overall volume decrease
      19% (P = 0.001). The average change in ventricular volume predicted which
      patients would require VPS placement, successfully identifying 7 of 10 patients
      (P = 0.004). Using an optimized cutoff of a change in ventricular volume of 2.5
      cm3 identified all patients who went on to require VPS placement (10 of 10; P =
      0.011). CONCLUSIONS: qCTV is a reliable means of quantifying ventricular volume
      and hydrocephalus. This technique offers a new tool for monitoring neurosurgical
      patients for hydrocephalus, and may be beneficial for use in future research
      studies, as well as in the routine care of patients with hydrocephalus.

PMID- 28456743
TI  - Does Objective Quality of Physicians Correlate with Patient Satisfaction Measured
      by Hospital Compare Metrics in New York State?
AB  - BACKGROUND: It is unclear whether publicly reported benchmarks correlate with
      quality of physicians and institutions. We investigated the association of
      patient satisfaction measures from a public reporting platform with performance
      of neurosurgeons in New York State. METHODS: This cohort study comprised patients
      undergoing neurosurgical operations from 2009 to 2013 who were registered in the
      Statewide Planning and Research Cooperative System database. The cohort was
      merged with publicly available data from the Centers for Medicare and Medicaid
      Services Hospital Compare website. Propensity-adjusted regression analysis was
      used to investigate the association of patient satisfaction metrics with
      neurosurgeon quality, as measured by the neurosurgeon's individual rate of
      mortality and average length of stay. RESULTS: During the study period, 166,365
      patients underwent neurosurgical procedures. Using propensity-adjusted
      multivariable regression analysis, we demonstrated that undergoing neurosurgical
      operations in hospitals with a greater percentage of patient-assigned "high"
      scores was associated with higher chance of being treated by a physician with
      superior performance in terms of mortality (odds ratio 1.90, 95% confidence
      interval 1.86-1.95), and a higher chance of being treated by a physician with
      superior performance in terms of length of stay (odds ratio 1.24, 95% confidence
      interval 1.21-1.27). Similar associations were identified for hospitals with a
      higher percentage of patients who claimed they would recommend these institutions
      to others. CONCLUSIONS: Merging a comprehensive all-payer cohort of neurosurgery
      patients in New York State with data from the Hospital Compare website, we
      observed an association of superior hospital-level patient satisfaction measures
      with objective performance of individual neurosurgeons in the corresponding
      hospitals.

PMID- 28456744
TI  - E-WIN Project 2016: Evaluating the Current Gender Situation in Neurosurgery
      Across Europe-An Interactive, Multiple-Level Survey.
AB  - BACKGROUND: The proportion of women among neurosurgeons appears to be growing
      worldwide with time. Official data concerning the current situation across Europe
      have not yet been published. Thus, there are still concerns about gender
      inequality. The European Women in Neurosurgery Project 2016 was designed to
      recognize the current situation across Europe. METHODS: The office holders of the
      national neurosurgical societies of 39 countries forming the European Association
      of Neurosurgical Societies were contacted to provide data stating the proportion
      of women in neurosurgery. Obtained data were supplied with the results of an
      online survey. RESULTS: The response rate of national office holders was 90%. The
      number of reported neurosurgeons was 12,985, and overall proportion of women
      represented was 12%. Two hundred thirty-seven responses to online questionnaire
      were taken into account. The overall proportion of female respondents was 30%.
      There was no intergender variability in responses regarding amount of working
      time per week, exposure to surgeries, or administrative work. Male respondents
      reported dedicating significantly more time to scientific work and feeling more
      confident dictating own career direction. Female respondents reported being less
      often married, having fewer children, a stronger perception of gender
      significance level, and a higher appreciation of personal qualities. CONCLUSIONS:
      Neurosurgery is a challenging field of medicine. The results of our survey did
      not imply an overall feeling of gender inequality among European respondents,
      although women believe that the gender issue to be more important than men do and
      that they have to sacrifice more of their personal lives.

PMID- 28456745
TI  - OPRM1 Methylation Contributes to Opioid Tolerance in Cancer Patients.
AB  - : Cancer patients in pain require high doses of opioids and quickly become opioid
      tolerant. Previous studies have shown that chronic cancer pain as well as high
      dose opioid use lead to mu-opioid receptor downregulation. In this study we
      explore downregulation of the mu-opioid receptor gene (OPRM1), as a mechanism for
      opioid tolerance in the setting of opioid use for cancer pain. We demonstrate in
      a cohort of 84 cancer patients that high-dose opioid use correlates with OPRM1
      hypermethylation in peripheral leukocytes of these patients. We then reverse
      translate our clinical findings by creating a mouse cancer pain model; we create
      opioid tolerance in the mouse cancer model to mimic opioid tolerance in the
      cancer patients. Using this model we determine the functional significance of
      OPRM1 methylation on cancer pain and opioid tolerance. We focus on 2 main cells
      within the cancer microenvironment: the cancer cell and the neuron. We show that
      targeted re-expression of mu-opioid receptor on cancer cells inhibits mechanical
      and thermal hypersensitivity, and prevents opioid tolerance, in the mouse model.
      The resultant analgesia and protection against opioid tolerance are likely due to
      preservation of mu-opioid receptor expression on the cancer-associated neurons.
      PERSPECTIVE: We demonstrate that epigenetic regulation of OPRM1 contributes to
      opioid tolerance in cancer patients, and that targeted gene therapy could treat
      cancer-induced nociception and opioid tolerance in a mouse cancer model.

PMID- 28456746
TI  - Genetically engineered mesenchymal stromal cells produce IL-3 and TPO to further
      improve human scaffold-based xenograft models.
AB  - Recently, NOD-SCID IL2Rgamma-/- (NSG) mice were implanted with human mesenchymal
      stromal cells (MSCs) in the presence of ceramic scaffolds or Matrigel to mimic
      the human bone marrow (BM) microenvironment. This approach allowed the
      engraftment of leukemic samples that failed to engraft in NSG mice without
      humanized niches and resulted in a better preservation of leukemic stem cell self
      renewal properties. To further improve our humanized niche scaffold model, we
      genetically engineered human MSCs to secrete human interleukin-3 (IL-3) and
      thrombopoietin (TPO). In vitro, these IL-3- and TPO-producing MSCs were superior
      in expanding human cord blood (CB) CD34+ hematopoietic stem/progenitor cells. MLL
      AF9-transduced CB CD34+ cells could be transformed efficiently along myeloid or
      lymphoid lineages on IL-3- and TPO-producing MSCs. In vivo, these genetically
      engineered MSCs maintained their ability to differentiate into bone, adipocytes,
      and other stromal components. Upon transplantation of MLL-AF9-transduced CB CD34+
      cells, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)
      developed in engineered scaffolds, in which a significantly higher percentage of
      myeloid clones was observed in the mouse compartments compared with previous
      models. Engraftment of primary AML, B-cell ALL, and biphenotypic acute leukemia
      (BAL) patient samples was also evaluated, and all patient samples could engraft
      efficiently; the myeloid compartment of the BAL samples was better preserved in
      the human cytokine scaffold model. In conclusion, we show that we can genetically
      engineer the ectopic human BM microenvironment in a humanized scaffold xenograft
      model. This approach will be useful for functional study of the importance of
      niche factors in normal and malignant human hematopoiesis.

PMID- 28456747
TI  - BLOS2 maintains hematopoietic stem cells in the fetal liver via repressing Notch
      signaling.
AB  - During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in
      the fetal liver (FL) after their emergence in the aorta-gonad-mesonephros (AGM)
      region. We recently reported that the endolysosomal trafficking factor BLOS2,
      encoded by the Bloc1s2 gene, regulates HSC/hematopoietic progenitor cell
      emergence in the AGM region; however, whether it plays a role in the FL remains
      unknown. Here, we show that BLOS2 plays an essential role in the regulation of
      HSC proliferation and differentiation in the FL. Bloc1s2 depletion leads to
      elevated Notch signaling, with an increased frequency but weakened self-renewal
      ability of FL HSCs. Functional assays show that Bloc1s2-/- FL HSCs harbor
      impaired lymphoid and myeloid differentiation abilities. These findings reveal
      that balanced control of Notch signaling by BLOS2 is required for HSC homeostasis
      during FL hematopoiesis.

PMID- 28456748
TI  - Reprogramming acute myeloid leukemia into sensitivity for retinoic-acid-driven
      differentiation.
AB  - The success of all-trans retinoic acid (ATRA) therapy for acute promyelocytic
      leukemia (APL) provides a rationale for using retinoic acid (RA)-based therapy
      for other subtypes of acute myeloid leukemia (AML). Recently, several studies
      showed that ATRA may drive leukemic cells efficiently into differentiation and/or
      apoptosis in a subset of AML patients with an NPM1 mutation, a FLT3-ITD, an IDH1
      mutation, and patients overexpressing EVI-1. Because not all patients within
      these molecular subgroups respond to ATRA and clinical trials that tested ATRA
      response in non-APL AML patients have had disappointing results, the
      identification of additional biomarkers may help to identify patients who
      strongly respond to ATRA-based therapy. Searching for response biomarkers might
      also reveal novel RA-based combination therapies with an efficient
      differentiation/apoptosis-inducing effect in non-APL AML patients. Preliminary
      studies suggest that the epigenetic or transcriptional state of leukemia cells
      determines their susceptibility to ATRA. We hypothesize that reprogramming by
      inhibitors of epigenetic-modifying enzymes or by modulation of microRNA
      expression might sensitize non-APL AML cells for RA-based therapy. AML relapse is
      caused by a subpopulation of leukemia cells, named leukemic stem cells (LSCs),
      which are in a different epigenetic state than the total bulk of the AML. The
      survival of LSCs after therapy is the main cause of the poor prognosis of AML
      patients, and novel differentiation therapies should drive these LSCs into
      maturity. In this review, we summarize the current knowledge on the epigenetic
      aspects of susceptibility to RA-induced differentiation in APL and non-APL AML.

PMID- 28456749
TI  - Lipid based nanocarriers system for topical delivery of photosensitizers.
AB  - Topical photodynamic therapy (PDT) is a non-invasive technique used in the
      treatment of malignant and non-malignant skin diseases. It offers great promise
      because of its simplicity, enhanced patient compliance, localisation of the
      photosensitizer, as well as the use of light and oxygen to achieve
      photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its
      clinical application is limited by poor penetration of photosensitizers through
      the skin. Therefore, much effort has been made to develop nanocarriers that can
      tackle the challenges of conventional photosensitizer-mediated PDT for topical
      delivery. This review discusses recent data on the use of different types of
      lipid-based nanocarriers in delivering photosensitizer for topical PDT.

PMID- 28456750
TI  - Accelerating biomedical innovation: a case study of the SPARK program at Stanford
      University, School of Medicine.
AB  - Translating academic medical research into new therapies is an important
      challenge for the biopharmaceutical industry and investment communities, which
      have historically favored later-stage assets with lower risk and clearer
      commercial value. The Stanford SPARK program is an innovative model for
      addressing this challenge. The program was created in 2006 to educate students
      and faculty about bringing academic research from bench to bedside. Every year,
      the program provides mentorship and funding for approximately a dozen SPARK
      'scholars,' with a focus on impacting patient lives, regardless of economic
      factors. By reviewing the detailed structure, function and operation of SPARK we
      hope to provide a template for other universities and institutions interested in
      de-risking and facilitating the translation of biomedical research.

PMID- 28456752
TI  - Use of high or low FiO2 during initial resuscitation did not impact survival or
      neurodevelopmental outcomes of preterm infants.

PMID- 28456753
TI  - Severe hypercalcaemia and hypophosphataemia with an optimised preterm parenteral
      nutrition formulation in two epochs of differing phosphate supplementation.
AB  - OBJECTIVE: To compare in two epochs of differing phosphate provision serum
      calcium, phosphate, potassium, and sodium concentrations and the frequency of
      abnormality of these electrolytes and of sepsis in preterm infants who received
      an optimised higher amino acid-content formulation. DESIGN AND SETTING:
      Retrospective cohort study at a single tertiary-level neonatal unit. PATIENTS:
      Preterm infants given parenteral nutrition (PN) in the first postnatal week
      during two discrete 6-month epochs in 2013-2014. INTERVENTIONS: In epoch 1 the
      Ca2+:PO4 molar ratio of the PN formulation was ~1.3-1.5:1 (1.7 mmol Ca2+ and 1.1
      mmol PO4 per 100 mL aqueous phase) and in epoch 2 was 1.0:1 via extra phosphate
      supplementation (1.7 mmol Ca2+ and 1.7 mmol PO4 per 100 mL). MAIN OUTCOME
      MEASURES: Peak calcium and nadir phosphate and potassium concentrations, and
      proportions with severe hypercalcaemia (Ca2+ >3.0 mmol/L), hypophosphataemia
      (PO4<1.5 mmol/L), and hypokalaemia (K+ <3.5 mmol/L) within the first postnatal
      week. RESULTS: In epoch 2, peak calcium concentrations were lower than in epoch 1
      (geometric means: 2.83 mmol/L vs 3.09 mmol/L, p value<0.0001), fewer babies were
      severely hypercalcaemic (10/49, 20%, vs 31/51, 61%, p value<0.0001); nadir plasma
      phosphate concentrations were higher (means: 1.54 mmol/L vs 1.32 mmol/L, p
      value=0.006), and there were fewer cases of hypophosphataemia (17/49, 35% vs
      31/51, 61%, p value=0.009) and hypokalaemia (12/49, 25% vs 23/51, 45%, p
      value=0.03). CONCLUSIONS: Reverting from a PN Ca2+:PO4 molar ratio of 1.3-1.5:1
      to a ratio of 1.0:1 was associated with a lower incidence and severity of
      hypophosphataemia and hypercalcaemia. For preterm infants given higher
      concentrations of amino acids (>=2.5 g/kg/day) from postnatal day 1, an equimolar
      Ca2+:PO4 ratio may be preferable during the first postnatal week.

PMID- 28456754
TI  - Sex-related differences in atrial fibrillation: can we discern true disparities
      from biases?

PMID- 28456751
TI  - Methods, Tools and Current Perspectives in Proteogenomics.
AB  - With combined technological advancements in high-throughput next-generation
      sequencing and deep mass spectrometry-based proteomics, proteogenomics, i.e. the
      integrative analysis of proteomic and genomic data, has emerged as a new research
      field. Early efforts in the field were focused on improving protein
      identification using sample-specific genomic and transcriptomic sequencing data.
      More recently, integrative analysis of quantitative measurements from genomic and
      proteomic studies have identified novel insights into gene expression regulation,
      cell signaling, and disease. Many methods and tools have been developed or
      adapted to enable an array of integrative proteogenomic approaches and in this
      article, we systematically classify published methods and tools into four major
      categories, (1) Sequence-centric proteogenomics; (2) Analysis of proteogenomic
      relationships; (3) Integrative modeling of proteogenomic data; and (4) Data
      sharing and visualization. We provide a comprehensive review of methods and
      available tools in each category and highlight their typical applications.

PMID- 28456756
TI  - What is lost in the acupuncture trial when using a sham intervention?

PMID- 28456755
TI  - Light-chain cardiac amyloidosis: strategies to promote early diagnosis and
      cardiac response.
AB  - Amyloid light chain (AL) amyloidosis is a systemic disease characterised by the
      aggregation of misfolded immunoglobulin light chain (LC), predominantly in the
      heart and kidneys, causing organ failure. If untreated, the median survival of
      patients with cardiac AL amyloidosis is 6 months from the onset of heart failure.
      Protracted time to establish a diagnosis, often lasting >1 year, is a frequent
      factor in poor treatment outcomes. Cardiologists, to whom patients are often
      referred, frequently miss the opportunity to diagnose cardiac AL amyloidosis.
      Nearly all typical cardiac support measures, with the exception of diuretics, are
      ineffective and may even worsen clinical symptoms, emphasising the need for
      accurate diagnosis. Patients with severe cardiac involvement face poor outcomes;
      heart transplantation is rarely an option because of multiorgan involvement,
      rapid clinical decline and challenges in predicting which patients will respond
      to treatment of the underlying plasma cell disorder. Early diagnosis and prompt
      treatment with Aca'!Eoesource therapiesAca'!a"c that limit the production of
      amyloidogenic LC are associated with better survival and improvement in organ
      function after a median of 2.4 months following haematological complete response.
      However, organ recovery is often incomplete because these source therapies do not
      directly target deposited amyloid. Emerging amyloid-directed therapies may
      attenuate, and potentially reverse, organ dysfunction by clearing existing
      amyloid and inhibiting fibril formation of circulating aggregates. Improved
      recognition of AL amyloidosis by cardiologists allows for earlier treatment and
      improved outcomes.

PMID- 28456757
TI  - Panniculus morbidus: obesity-related abdominal wall lymphoedema.
AB  - A 52-year-old female patient presented with a massive abdominal wall swelling
      that adversely affected her lifestyle. Imaging revealed significant subcutaneous
      oedema and the presence of grossly distended veins. Subsequently, she underwent a
      'toilet' panniculectomy and abdominoplasty. We describe the surgical technique
      used to retract the lymphoedematous tissue facilitating excisional surgery, and
      discuss the pathophysiology of this condition and the possible contribution of
      venous obstruction to the development of subcutaneous oedema.

PMID- 28456758
TI  - A case of fulminant necrotising fasciitis.

PMID- 28456759
TI  - Scalp vein sign: a forgotten clinical clue?

PMID- 28456760
TI  - Grassy biomes: An inconvenient reality for large-scale forest restoration? A
      comment on the essay by Chazdon and Laestadius.

PMID- 28456761
TI  - Long-distance dispersal explains the bipolar disjunction in Carex macloviana.
AB  - PREMISE OF THE STUDY: The sedge Carex macloviana d'Urv presents a bipolar
      distribution. To clarify the origin of its distribution, we consider the four
      main hypotheses: long-distance dispersal (either by mountain hopping or by direct
      dispersal), vicariance, parallel evolution, and human introduction. METHODS:
      Phylogenetic, phylogeographic, and divergence time estimation analyses were
      carried out based on two nuclear ribosomal (ETS and ITS) regions, one nuclear
      single copy gene (CATP), and three plastid DNA regions (rps16 and 5'trnK introns,
      and psbA-trnH spacer), using Bayesian inference, maximum likelihood, and
      statistical parsimony. Bioclimatic data were used to characterize the climatic
      niche of C. macloviana. KEY RESULTS: Carex macloviana constitutes a paraphyletic
      species, dating back to the Pleistocene (0.62 Mya, 95% highest posterior density:
      0.29-1.00 Mya). This species displays strong genetic structure between
      hemispheres, with two different lineages in the Southern Hemisphere and limited
      genetic differentiation in Northern Hemisphere populations. Also, populations
      from the Southern Hemisphere show a narrower climatic niche with regards to the
      Northern Hemisphere populations. CONCLUSIONS: Carex macloviana reached its
      bipolar distribution by long-distance dispersal, although it was not possible to
      determine whether it was caused by mountain hopping or by direct dispersal. While
      there is some support that Carex macloviana might have colonized the Northern
      Hemisphere by south-to-north transhemisphere dispersal during the Pleistocene,
      unlike the southwards dispersal pattern inferred for other bipolar Carex L.
      species, we cannot entirely rule out north-to-south dispersion.

PMID- 28456762
TI  - Nature's potato chip: The role of salty fungi in a changing world.

PMID- 28456763
TI  - Female white-collar workers remain at higher risk of breast cancer after
      adjustments for individual risk factors related to reproduction and lifestyle.
AB  - OBJECTIVES: The aim was to investigate the variation in risk of breast cancer
      between occupational groups with a focus on white-collar and blue-collar workers
      and to investigate to what extent the differences were explained by risk factors
      related to reproduction and lifestyle. METHODS: Between 1991 and 1996, 14 119
      women born between 1923 and 1950 and residents of Malmo, Sweden, were included in
      this cohort study. Individual data on risk factors (eg, age, parity, age at first
      child, months of breast feeding per child, hormonal replacement therapy, physical
      activity, alcohol consumption, smoking, height and body mass index) and
      occupational history were assessed using a questionnaire. First-time diagnoses of
      invasive breast cancer were identified through the Swedish Cancer Registry up
      until 31 December 2013. RESULTS: A total of 897 women were diagnosed with breast
      cancer. Analyses adjusted for age showed an increased risk for white-collar
      workers compared with blue-collar workers and indicated higher risks in the
      occupational categories: professionals, administrative and bookkeeping than among
      women in sales, transportation, production and service work. This difference was
      only marginally attenuated after adjustment for an extensive set of risk factors
      related to reproduction and lifestyle. CONCLUSION: Reproductive and lifestyle
      factors explain only a minor part of the increased risk of breast cancer in white
      collar workers. Further studies are needed to investigate the remaining factors
      for the difference in risk between occupational groups.

PMID- 28456764
TI  - The prevalence of radiographic and MRI-defined patellofemoral osteoarthritis and
      structural pathology: a systematic review and meta-analysis.
AB  - BACKGROUND: Patellofemoral osteoarthritis (PF OA) is more prevalent than
      previously thought and contributes to patient's suffering from knee OA. Synthesis
      of prevalence data can provide estimates of the burden of PF OA. OBJECTIVE: This
      study aims to conduct a systematic review and meta-analysis on the prevalence of
      PF OA and structural damage based on radiography and MRI studies in different
      populations. METHODS: We searched six electronic databases and reference lists of
      relevant cross-sectional and observational studies reporting the prevalence of PF
      OA. Two independent reviewers appraised methodological quality. Where possible,
      data were pooled using the following categories: radiography and MRI studies.
      RESULTS: Eighty-five studies that reported the prevalence of patellofemoral OA
      and structural damage were included in this systematic review. Meta-analysis
      revealed a high prevalence of radiographic PF OA in knee pain or symptomatic knee
      OA (43%), radiographic knee OA or at risk of developing OA (48%) and radiographic
      and symptomatic knee OA (57%) cohorts. The MRI-defined structural PF damage in
      knee pain or symptomatic population was 32% and 52% based on bone marrow lesion
      and cartilage defect, respectively. CONCLUSION: One half of people with knee pain
      or radiographic OA have patellofemoral involvement. Prevalence of MRI findings
      was high in symptomatic and asymptomatic population. These pooled data and the
      variability found can provide evidence for future research addressing risk
      factors and treatments for PF OA. TRIAL REGISTRATION NUMBER: PROSPERO systematic
      review protocol (CRD42016035649).

PMID- 28456765
TI  - The skeletal and heart muscle triacylglycerol lipolysis revisited.
AB  - For 40 years, the enzyme hormone sensitive lipase was considered to hydrolyze the
      first ester bond of the triacylglycerol moiety and thus initiate hydrolysis.
      However, 12 years ago a new lipolytic enzyme, termed adipose triglyceride lipase
      was discovered. It was further shown that the process of lipolysis of
      triacylglycerol to diacylglycerol and fatty acid is initiated by adipose
      triglyceride lipase and not by hormone sensitive lipase, responsible for
      hydrolysis of diacylglycerol to monoacyglycerol and fatty acid. Adipose
      triglyceride lipase is present in all types of cells containing neutral fat. The
      enzyme is activated by a protein called comparative gene identification-58 and
      inhibited by a protein called G0/G1 switch protein 2. It has also been discovered
      that perilipins, the main proteins coating lipid droplets in the cells, are
      involved in the process of triacylglycerol lipolysis. Five perilipins (1-5) were
      identified, however, up to now their role has been poorly assessed. In skeletal
      muscles, exercise and training affect the mRNA expression and protein content of
      adipose triglyceride lipase, comparative gene identification-58, G0/G1 switch
      protein 2, perilipin 2 and 5. The effect of exercise/training depends on exercise
      intensity and type of muscle fiber. An interaction between comparative gene
      identification-58 and adipose triglyceride lipase seems to be responsible for the
      enzyme activation during contractile activity. Adipose triglyceride lipase is
      also responsible for the activation of the first step of triacylglycerol
      lipolysis in the heart. There is substantial evidence that cardiac
      triacylglycerol metabolism affects the function of the heart. ATGL gene mutations
      leads to the development of neutral lipid storage diseases.

PMID- 28456766
TI  - Understanding mitotane mode of action.
AB  - Adrenocortical carcinoma is a rare disease with poor prognosis. Mitotane is the
      most effective agent in post-operative treatment (or when inoperable). It
      selectively limits growth and bioactivity of adrenal tissue. Despite 60 years of
      use, the basis for its action has yet to be convincingly established. This review
      summarizes current knowledge of mitotane effects, based on studies on adrenal
      tissue and primary cell cultures, with emphasis on more recent studies of cell
      lines. We consider features of the adrenal cortex that might explain mitotane
      selectivity, and review effects on non-adrenal cells. Since the most clear-cut
      mitotane effects have been observed for mitochondria, this topic is the core of
      the review. Mitochondria present unique characteristics in steroidogenic tissue
      and are known to be important in malignancy development and apoptosis. We look at
      the evidence for mitotane activation within mitochondria, its impact on
      mitochondrial energy metabolism and other cellular processes as well as on
      downstream effects in the cell, such as apoptosis initiation. Further genomic and
      proteomic investigative studies are likely to yield useful results.

PMID- 28456767
TI  - St36 electroacupuncture activates nNOS, iNOS and ATP-sensitive potassium channels
      to promote orofacial antinociception in rats.
AB  - Orofacial pain is pain perceived in the face and/or oral cavity, generally caused
      by diseases or disorders of regional structures, by dysfunction of the nervous
      system, or through referral from distant sources. Treatment of orofacial pain is
      mainly pharmacological, but it has increased the number of reports demonstrating
      great clinical results with the use of non-pharmacological therapies, among them
      electroacupuncture. However, the mechanisms involved in the electroacupuncture
      are not well elucidated. Thus, the present study investigate the involvement of
      the nitric oxide synthase (NOS) and ATP sensitive K+ channels (KATP) in the
      antinociception induced by electroacupuncture (EA) at acupoint St36. Thermal
      nociception was applied in the vibrissae region of rats, and latency time for
      face withdrawal was measured. Electrical stimulation of acupoint St36 for 20
      minutes reversed the thermal withdrawal latency and this effect was maintained
      for 150 min. Intraperitoneal administration of specific inhibitors of neuronal
      nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and a KATP
      channels blocker reversed the antinociception induced by EA. Furthermore, nitrite
      concentration in cerebrospinal fluid (CSF) and plasma, increased 4 and 3-fold
      higher, respectively, after EA. This study suggests that NO participates of
      antinociception induced by EA by nNOS, iNOS and ATP-sensitive K+ channels
      activation.

PMID- 28456768
TI  - Corticotropin releasing factor receptor 1 antagonist differentially inhibits
      freezing behavior and changes gamma-aminobutyric acidergic activity in the
      amygdala in low- and high-anxiety rats.
AB  - The aim of this study was to examine the effects of non-peptide corticotropin
      releasing factor receptor 1 (CRF1) antagonist (antalarmin) administration on rat
      conditioned fear responses and gamma-aminobutyric acid (GABA)-ergic brain
      activity (GAD67 expression and GABA concentration) in low-anxiety (LR) and high
      anxiety (HR) rats. The animals were divided into the LR and HR groups based on
      the duration of their conditioned freezing response in the first contextual fear
      test. After 28 days, the animals were re-subjected to the contextual fear
      training and test. The rats received an antalarmin injection (10 mg/kg or 20
      mg/kg) 80 min before the second exposure to the aversive context. Antalarmin
      significantly attenuated the conditioned fear response only in the HR rats. The
      behavioral effect of a lower dose (10 mg/kg) of antalarmin was accompanied by
      increased GAD67 expression in the prelimbic cortex (PL) and central nucleus of
      the amygdala (CeA) and an increased GABA concentration in the amygdala. These
      studies showed that HR rats were more susceptible to the anxiolytic effects of
      CRF1 antagonist administration, which were associated with increased GABAergic
      activity in the medial prefrontal cortex and amygdala. The current data may
      provide insights into the neurobiological mechanism operating within the
      mesolimbic CRF-GABA neurotransmitter systems, which may be responsible for
      individual differences in stress-related diseases. This knowledge can be applied
      to further elucidate the pathophysiology of anxiety and trauma/stress-related
      disorders.

PMID- 28456769
TI  - Neuroprotective effect of resveratrol against late cerebral ischemia reperfusion
      induced oxidative stress damage involves upregulation of osteopontin and
      inhibition of interleukin-1beta.
AB  - This study was carried out to investigate the expression pattern and role of
      osteopontin (OPN) in late global ischemia-reperfusion (I/R) injury with or
      without resveratrol (RES) pre-treatment. Young male rats were divided into 3
      groups (n = 12) of I) sham, II) I/R model group and III) I/R + RES. Vehicle and
      RES (20 mg/kg) were administered to designed groups intraperitoneally 30 days
      prior global I/R injury (2-VO) induction and continued for 7 days, later. Then,
      percentages of infarct areas, mRNA levels of OPN, inducible nitric oxide synthase
      (iNOS) and other biochemical parameter related to endogenous antioxidants
      activities and inflammation were measured in the cerebral cortices of all groups.
      Significant elevations in the levels of malondialdehyde (MDA), the inflammatory
      mediator interleukin 1beta (IL-1beta), chemokines (KC and MIP-2) and adhesive
      molecules (ICAM-1) as well as parallel reductions in enzymes activities of
      superoxide dismutase (SOD), glutathione peroxidase (GPx) and chloramphenicol
      acetyltransferase (CAT) were observed in the cerebral homogenates of rats with
      late I/R injury. Associated with these changes, mRNA levels of OPN were
      significantly downregulated and those of iNOS and Bax were upregulated. All these
      changes were reversed by in 2-VO I/R induced rats pre-administered RES. These
      findings suggest that inhibition of sustained inflammatory response driven by IL
      1beta, decreased activities of endogenous antioxidants and downregulation of OPN
      induced upregulation of iNOS play important roles in the pathogenesis of
      neurodegeneration during late cerebral I/R injury, effects that can be modulated
      by RES which might explain its neuroprotection effect during late global
      ischemia.

PMID- 28456770
TI  - Safety and efficacy of intravenous cyclophosphamide pulse therapy in therapy
      refractory Crohn's disease patients.
AB  - A major challenge in the management of persistently active Crohn's disease
      patient's refractory to treatment regimen following the current guidelines is the
      induction of remission, which is a prerequisite for subsequent maintenance
      therapy. The aim of this study was to evaluate both the clinical and endoscopic
      benefit of intravenous cyclophosphamide pulse therapy in patients with active and
      therapy refractory Crohn's disease. Nine patients with acute moderate to severe
      Crohn's disease, not responding to conventional as well as biological therapy
      regimen received 3 - 9 cycles of monthly treatments with intravenous
      cyclophosphamide (680 - 1000 mg) in an uncontrolled setting and were
      retrospectively analyzed. Eight of nine patients (88.9%) had a clinical response
      (measured by a decrease in the Harvey-Bradshaw index, HBI >= 3) and two of nine
      patients (22.2%) achieved clinical remission (HBI <= 4) at week 8 after two
      applications of intravenous cyclophosphamide therapy. These response and
      remission rates remained unchanged after individual completion of
      cyclophosphamide therapy. Median HBI decreased from 18 (7 - 25) at the beginning
      of therapy to 7 (3 - 18) at week 8. 5 of 9 patients (56%) showed endoscopic
      response (defined by a reduction of ulcers) and one patient (11%) reached
      endoscopic remission (defined by the absence of ulcers) after the last
      application of cyclophosphamide. Arthralgia, which was present in 4 of 9 (44%)
      patients, was unchanged in most patients after cyclophosphamide therapy, although
      one patient described a marked reduction in joint pain. Cyclophosphamide pulse
      therapy was well tolerated during the whole treatment course in all subjects. One
      patient with long-standing Crohn's disease was diagnosed with a high-grade
      intraepithelial neoplasia in the rectum and underwent surgical intervention,
      where the diagnosis of an early stage adenocarcinoma was made. We concluded that
      intravenous cyclophosphamide pulse therapy was well tolerated by most patients
      and effective for inducing clinical and endoscopic response and remission in
      patients with therapy refractory Crohn's disease. In patients who are
      unresponsive to available therapies, including available biological treatment
      options, cyclophosphamide therefore represents a potential option to induce
      therapeutic response, which must then be maintained by other treatment
      modalities.

PMID- 28456771
TI  - Anti-inflammatory effects of simvastatin in nonsteroidal anti-inflammatory drugs
      induced small bowel injury.
AB  - Small bowel injury can occur as the result of a multifaceted process that
      includes increased acid secretion, generation of reactive oxygen species, and
      cyclooxygenase inhibition. However, no effective medication for small bowel
      ulceration is available. Simvastatin is an important lipid-lowering agent with
      anti-inflammatory activity. We aimed to validate the effects of simvastatin in
      vitro and in vivo. In presence or absence of simvastatin, IEC-6 small bowel cell
      line with 50 ng/ml of tumor nectosis factor alpha (TNF-alpha) was investigated by
      western blotting, qRT-PCR, and DCF-DA assay. In addition, an in vivo study of
      nonsteroidal anti-inflammatory drugs (NSAID)-induced small bowel inflammation was
      performed using 7-week-old specific-pathogen-free (SPF) male C57BL/6 mice.
      Simvastatin treatment reduced the mRNA levels of interleukin-6 and interleukin-8
      by approximately 50% in TNF-alpha-stimulated IEC-6 cells. Treatment with a
      combination of 50 ng/ml TNF-alpha and MUM simvastatin decreased activation of
      Akt, IkappaBalpha, and nuclear factor-kappaB p65 level in IEC-6 cells. By DCF-DA
      staining, intracellular reactive oxygen species (ROS) production was increased in
      TNF-alpha-stimulated cells, and treatment with simvastatin decreased the level of
      ROS. In addition, in vivo mouse model of NSAID-induced small bowel inflammation,
      the administration of simvastatin reduced the number of small bowel hemorrhagic
      lesions and the level of ROS production as determined by gross examination and 8
      hydroxydeoxyguanosine immunohistochemistry of small bowel tissue, respectively.
      Simvastatin reduced NSAID-induced injuries by both suppression of ROS generation
      and modulation of inflammatory cytokines in vitro and in vivo. Therefore,
      simvastatin, an HMG-CoA reductase inhibitor, has potential as a prophylactic and
      therapeutic agent for NSAID-induced small bowel injury.

PMID- 28456772
TI  - Lafutidine, a histamine H2 receptor antagonist with mucosal protective
      properties, attenuates 5-fluorouracil-induced intestinal mucositis in mice
      through activation of extrinsic primary afferent neurons.
AB  - Intestinal mucositis accompanied by severe diarrhea is one of the most common
      side effects during cancer chemotherapy. Lafutidine, a histamine H2 receptor
      antagonist with mucosal protective properties via sensory afferent neurons, is
      used for the treatment of upper gastrointestinal diseases. The present study
      investigated the effects of lafutidine on 5-fluorouracil (5-FU)-induced
      intestinal mucositis induced in mice. Male C57BL/6 wild-type (WT), sensory
      deafferented mice, and transient receptor potential vanilloid subfamily 1
      knockout (TRPV1KO) mice were used. Animals were administered 5-FU once daily,
      while lafutidine and famotidine were administered twice daily for 6 days.
      Repeated administration of 5-FU caused severe intestinal mucositis, characterized
      by shortening of villi and destruction of crypts and was accompanied by diarrhea
      and body weight loss. Daily administration of lafutidine reduced the severity of
      intestinal mucositis, diarrhea and body weight loss in a dose-dependent manner,
      while famotidine had no effect on intestinal mucositis. The preventive effects of
      lafutidine were completely abolished in sensory deafferented and TRPV1-KO mice.
      Lafutidine significantly suppressed 5-FU-increased MPO activity and inflammatory
      cytokine expression on day 6, but not apoptosis induction in intestinal crypts on
      day 1. Lafutidine induced Alcian Blue and PAS-positive mucus production in the
      small intestine. These findings suggest that lafutidine attenuates 5-FU-induced
      intestinal mucositis, most likely by increasing mucus production via activation
      of sensory afferent neurons. Furthermore, intact TRPV1 signaling is essential for
      the activation of sensory afferent neurons induced by lafutidine. Therefore,
      lafutidine is more useful than other common antacids for the treatment of
      intestinal mucositis during cancer chemotherapy.

PMID- 28456773
TI  - Transforming growth factor-beta1 and tumor necrosis factor-alpha concentration in
      serum during disturbed lymph flow from a liver in rats.
AB  - In the last decades an increasing attention has been devoted to the role of
      lymphatic system in pathomechanism. The disturbed lymph flow from a liver
      contributes to liver fibrogenesis and probably to hepatocirrhosis. Cytokines play
      a major role in the development of hepatic fibrosis, the wound-healing response
      of the liver to chronic injury. Cytokines in hepatic fibrogenesis may be pro- or
      antifibrogenic. Transforming growth factor-beta1 (TGF-beta1) is pro-fibrogenic
      cytokine and plays a key role in liver fibrogenesis. Interferon-gamma (INF-gamma)
      is anti-fibrogenic by downregulating hepatic stellate cell activation. We
      described the negative correlation between tumor necrosis factor-alpha (TNF
      alpha) and IFN-gamma concentration in serum during disturbed lymph flow from a
      liver of rats. TNF-alpha plays a antifibrogenic role in liver fibrogenesis too.
      Male Albino Wistar rats weighing 250 - 300 grams were selected for the
      experiment. The animals were kept in stable condition and were fed a standard
      diet with no fluid restriction. The rats were divided into 3 groups: group B -
      mechanical insufficiency was obtained by ligation of hepatic trunc, group K -
      underwent sham operation, group 0 - rats not subjected to any surgery. The
      animals were sacrificed for experiment in 1, 3, 7, 14, 21, 28, 35, 56 and 103 day
      after operation. During experiment TGF-beta1 and TNF-alpha concentration in serum
      were assayed. We observed a positive correlation between TGF-beta1 and TNF-alpha
      concentration in serum. During disturbed lymph flow from the liver TNF-alpha
      plays probably a antifibrogenic role in liver fibrogenesis.

PMID- 28456774
TI  - Lung protection in cardio-pulmonary bypass.
AB  - Since the invention of the heart-lung machine paediatric cardiac surgery
      developed rapidly. For correction of complex cardiac malformations the
      application of a cardio-pulmonary bypass (CPB) has become indispensable but
      possible negative effects of this technique should not be neglected. Especially,
      both bypassed organs i.e. heart and lung are not perfused during the procedure
      and therefore are threatened by ischemia and reperfusion injury. Additionally,
      CPB was developed with a non-pulsatile flow but there are clinical observations
      that pulsatile flow might be superior with improved patient outcomes. Thus, the
      aim of our study was to evaluate the effect of CPB on lung structure and to
      assess whether different flow modalities (pulsatile vs. non-pulsatile flow) or
      application of the antibiotic minocycline might be advantageous. Thirty five
      piglets of four weeks age were examined and divided into five experimental
      groups: control (no CPB) without or with minocycline, CPB (non-pulsatile flow)
      without or with minocycline and CPB with pulsatile flow. CPB was performed for 90
      min followed by a 120 min reperfusion and recovery phase. Thereafter, adenosine
      triphosphate-content of lung biopsies and histology was carried out. We found
      that CPB was associated with a significant thickening of alveolar wall
      accompanied by an infiltration of neutrophil leucocytes. Moreover, markers for
      hypoxia, apoptosis, nitrosative stress, inflammation and DNA damage were
      significantly elevated after CPB. These cellular damages could be partially
      inhibited by minocycline or pulsatile flow. Both, minocycline and pulsatile flow
      attenuate lung damage after CPB.

PMID- 28456775
TI  - Atrial natriuretic peptide and brain natriuretic peptide changes after epicardial
      percutaneous left atrial appendage suture ligation using LARIAT device.
AB  - Percutaneous left atrial appendage closure is an alternative treatment for stroke
      and systemic thromboembolism risk reduction in non-valvular atrial fibrillation
      (AF). However, the neurohormonal impact of epicardial exclusion of the left
      atrial appendage (LAA) with the LARIAT procedure is unknown. Evaluation of
      changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)
      levels in AF patients underwent percutaneous LAA suture ligation. Sixty six
      patients underwent successfully percutaneous LAA suture ligation using LARIAT
      device. The level of ANP and BNP was measured before and 3 months after
      procedure. Mean ANP level before procedure was 249 +/- 77 pg/mL (range from 95
      pg/mL to 503 pg/mL) and mean BNP level was 481 +/- 517 pg/mL (range from 34 pg/mL
      to 2508 pg/mL). Three months after procedure mean ANP level was 249 +/- 79 pg/mL
      (range from 98 pg/mL to 492 pg/mL) and mean BNP level was 495 +/- 526 pg/mL
      (range from 52 pg/mL to 2420 pg/mL). At 3 months follow up after percutaneous LAA
      suture ligation there were no significant differences in ANP and BNP levels.

PMID- 28456776
TI  - Effect of sprint cycling and stretch-shortening cycle exercises on the
      neuromuscular, immune and stress indicators in young men.
AB  - Selection of optimal physical load is essential for desired adaptation including
      health benefits. We hypothesized that neuromuscular, immune and stress indicators
      will be higher after energy demanding sprint interval exercise (SIE) than to
      mechanically demanding stretch-shortening cycle exercise (SSE). The main aim of
      this study was to assess and compare the kinetics of blood brain-derived
      neurotrophic factor (BDNF), norepinephrine (NE) and cortisol (as stress
      indicators) and proinflammatory (IL-6) and anti-inflammatory (IL-10) cytokines
      within 24 hours after metabolically demanding SIE and after muscle damage
      inducing SSE. Twenty healthy physically active young men randomly assigned to two
      equal groups to complete 12 bouts of 5 s stationary cycling sprints every 3 min
      (SIE) or 200 drop-jumps with 30 s interval between each jump (SSE), respectively.
      Quadriceps muscle maximal voluntary contraction torque and voluntary activation
      and soreness were measured and blood samples collected before and 2 min, 1 hour,
      12 hours and 24 hours after the SIE and SSE. The BDNF, cortisol, IL-6 and NE
      levels increased more at 2 min after SIE than SSE (P < 0.05); however, the IL-10
      level did not differ between SIE and SSE. BDNF and cortisol levels were decreased
      at 24 h after both SIE and especially after SSE. The higher was the initial BDNF
      level, the greater was its decrease at 24 h after both type of exercise. Before
      exercise BDNF level correlated closely with the change in central fatigue
      (decrease in voluntary activation) after both SIE and SSE. We thus conclude that
      both metabolically demanding SIE and muscle damage inflicting SSE induced long
      lasting decrease in circulating BDNF which may not promote brain health. The
      level of circulating BDNF, but not cortisol, IL-6, IL-10 or NE, was associated
      with changes in central motor fatigue.

PMID- 28456777
TI  - Short-term changes of serum potassium concentration induced by physical exercise
      in patient with arterial hypertension treated with angiotensin-converting enzyme
      inhibitor alone or in combination with statin.
AB  - Intensive physical exercise may facilitate potassium release from skeletal
      muscles that may result in hyperkalemia. Commonly used drugs including
      angiotensin converting enzyme inhibitors (ACEI) and statins increase a risk of
      hyperkalemia. It is not known whether the effect of these drugs on serum
      potassium during physical exercise is additive. The study compared the effect of
      physical exercise on the changes of serum potassium in hypertensive patients
      receiving ACEI alone or in combination with statin. Eighteen patients with
      arterial hypertension with normal renal function were included in a prospective
      placebo-controlled cross-over study. The patients underwent 3 exercise tests on a
      bicycle ergometer with 55 - 60% of maximum oxygen consumption each lasting 30
      minutes, i.e. after being treated with ACEI alone for six months, and then in a
      random order after the administration of ACEI with statin or ACEI with placebo
      each time for eight weeks separated by 2-week wash-out. Serum potassium was
      measured with atomic emission flame spectrometry before and after 15 and 30
      minutes exercise and after 30-minute recovery. During the exercise serum
      potassium concentration increased moderately but significantly during all
      exercise tests. Mean serum potassium during exercise remained within the normal
      range. There were no differences in the exercise-induced changes of serum
      potassium during the exercise tests performed after ACEI combined with statin or
      with placebo. Addition of statin to ACEI does not increase the risk of
      hyperkalemia in hypertensive patients with preserved renal function during
      physical exercise with intensity typical for routine daily activities.

PMID- 28456778
TI  - Increased number of endothelial progenitors in peripheral blood as a possible
      early marker of tumour growth in post-menopausal breast cancer patients.
AB  - The aim of the study was to evaluate the number of circulating endothelial
      progenitor cells (circulating EPCs) in the blood of patients diagnosed with
      breast cancer and to make an attempt at finding associations with the number of
      circulating EPCs and selected clinic-pathological factors; TNM and histological
      grading, molecular subtype of breast cancer, hormonal status, the expression of
      Ki-67 and the size of tumour. The study involved 96 Caucasian ethnicity post
      menopausal women. Sixty-six women aged 48 - 63 (mean age 55) with breast cancer
      diagnosis without distant metastases (M0). The median value of the tumour
      diameter was 1.51 cm. The control group consisted of 30 healthy, non-smoking,
      post-menopausal women, mean age 49, range 44 - 54 years of age. The exclusion
      criteria for all the participants were hypertension, hyperlipidaemia, and
      hyperglycaemia, acute and chronic infection. With regard to the fresh blood
      samples the number of circulating endothelial progenitors was determined using
      flow cytometry. The fluorescence of 100,000 cells was measured during the
      analysis. Circulating EPCs were identified with the immune-phenotype CD45-,
      CD34+, CD133+, CD31+. A significantly higher number of circulating EPCs in the
      study group, as compared to the controls (P = 0.0001) and a significantly higher
      number of circulating EPCs in women over 60 with breast cancer than in the
      younger women (P = 0.0029) were reported. A positive correlation was noted
      between circulating EPCs and age as well as between circulating EPCs and HER-2 (P
      = 0.0231, P = 0.0414, respectively), and a negative correlation between
      circulating EPCs and histological grading of breast cancer (P = 0.0272). The
      study has shown a higher number of circulating EPCs in breast cancer patients,
      which indicates stimulation of neovascularization. Additionally, since bone
      morrow-derived circulating EPCs are more intensively mobilised in older and
      overweight breast cancer patients, we can speculate that more aggressive neo
      angiogenesis can occur in those patients.

PMID- 28456779
TI  - Effect of long-term culture on the biological and morphological characteristics
      of human adipose tissue-derived stem Cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells that can be obtained from
      different tissues, including bone marrow, adipose tissue, umbilical blood,
      Wharton's jelly, and dental pulp. Due to their differentiation potential,
      regenerative and immunosuppressive properties, as well as ability to expand under
      in vitro conditions, these cells represent a promising therapeutic tool for
      regenerative medicine. However, the basic prerequisite for the therapeutic
      utilization of MSCs is obtaining a sufficient amount. While this may be achieved
      by prolonged cultivation, long-term culture of MSCs is associated with
      accumulation of morphological and functional changes. In our study, we focused on
      analyzing morphological and biological changes of cultured adipose tissue-derived
      stem cells over 30 passages. We performed morphological analysis using light and
      electron microscopy, as well as analysis of selected biological properties
      (expression of surface antigens and selected genes involved in cell regulation
      and apoptosis, cell cycle, and cell senescence) every 5 passages. Our results
      showed that long-term expansion leads to significant changes in morphology and
      affects proliferation kinetics and the cell cycle. On the other hand, the MSCs
      maintained a prototypical immunophenotype, normal cell cycle and apoptosis
      regulator function, and maintained a low level of telomerase activity during
      later passages.

PMID- 28456780
TI  - Integrating exposure to palliative care in an undergraduate medical curriculum:
      student perspectives and strategies.

PMID- 28456781
TI  - Quality indicators for learner-centered postgraduate medical e-learning.
AB  - Objectives: The objectives of this study were to identify the needs and
      expectations of learners and educational experts in postgraduate medical e
      learning, and to contribute to the current literature. Methods: We performed four
      focus-group discussions with e-learning end-users (learners) and didactic
      experts. The participants were postgraduate learners with varying levels of
      experience, educational experts from a Dutch e-learning task group, and
      commercial experts from a Dutch e-learning company. Verbatim transcribed
      interview recordings were analyzed using King's template analysis. The initial
      template was created with reference to recent literature on postgraduate medical
      e-learning quality indicators. The transcripts were coded, after which the
      emerging differences in template interpretation were discussed until a consensus
      was reached within the team. Results: The final template consisted of three
      domains of positive e-learning influencers (motivators, learning enhancers, and
      real-world translation) and three domains of negatively influential parameters
      (barriers, learning discouragers, and poor preparation). The interpretation of
      the final template showed three subjects which form the basis of e-learning,
      namely, Motivate, Learn and Apply. Conclusions: This study forms a basis for
      learning in general and could be applied to many educational instruments.
      Individual characteristics should be adapted to the target audience. Three
      subjects form the basis of, and six themes cover all items needed for, good
      (enough) postgraduate e-learning. Further research should be carried out with
      learners and real-world e-learning to validate this template.

PMID- 28456782
TI  - Salmonella mediated the hemagglutinating virus of Japan-envelope transfer
      suppresses tumor growth.
AB  - Salmonella can target to tumor microenvironments after systemic treatment. The
      hemagglutinating virus of Japan-envelope (HVJ-E) induced apoptosis in tumor cells
      without toxicity in normal cells. Current HVJ-E therapeutic strategies, aimed at
      using HVJ-E for intratumor treatment, have shown great promise in animal models
      but have achieved only limited systemic treatment. The purpose of this study was
      to investigate the modulation of the anti-tumor efficiency of HVJ-E by coating
      the particles with poly (allylamine hydrochloride) (PAH), designated as P-HVJ-E.
      Treatment with P-HVJ-E resulted in decreased hemagglutinating activity and
      maintained tumor cell-selective apoptosis and anti-tumor immunity. The use of
      Salmonella as a coating for P-HVJ-E (PHS) enhanced the antitumor activity and
      maintained the tumor-targeting activity. Treatment with PHS resulted in delayed
      tumor growth in tumor-bearing mice. Furthermore, a Western blot assay of the
      tumors revealed that HVJ-E targeted to the tumor after systemic treatment with
      PHS. These results indicate that Salmonella coating viral particles may provide a
      new approach for tumor therapy.

PMID- 28456783
TI  - Galphai3 nuclear translocation causes irradiation resistance in human glioma
      cells.
AB  - We have previously shown that Galphai3 is elevated in human glioma, mediating Akt
      activation and cancer cell proliferation. Here, we imply that Galphai3 could also
      be important for irradiation resistance. In A172 human glioma cells, Galphai3
      knockdown (by targeted shRNAs) or dominant-negative mutation significantly
      potentiated irradiation-induced cell apoptosis. Reversely, forced over-expression
      of wild-type or constitutively-active Galphai3 inhibited irradiation-induced A172
      cell apoptosis. Irradiation in A172 cells induced Galphai3 translocation to cell
      nuclei and association with local protein DNA-dependent protein kinase (DNA-PK)
      catalytic subunit. This association was important for DNA damage repair. Galphai3
      knockdown, depletion (using Galphai3 knockout MEFs) or dominant-negative mutation
      potentiated irradiation-induced DNA damages. On the other hand, expression of the
      constitutively-active Galphai3 in A172 cells inhibited DNA damage by irradiation.
      Together, these results indicate a novel function of Galphai3 in irradiation
      resistance in human glioma cells.

PMID- 28456784
TI  - Near-infrared photoimmunotherapy: a comparison of light dosing schedules.
AB  - Near infrared photoimmunotherapy (NIR-PIT) is a newly-developed cancer therapy in
      which a monoclonal antibody is conjugated to a near-infrared photoabsorber, IR700
      to form an antibody photoabsorber conjugate (APC). After the APC binds to cancer
      cells expressing the cognate antigen, exposure to NIR light results in rapid,
      highly selective necrotic cell death of the cancer cells with minimal off-target
      effects. Several hours after NIR-PIT, the tumor vessels become
      supraphysiologically permeable and circulating APC can therefore readily leak
      into the already-treated tumor space where it can bind with viable cancer cells
      that is called super-enhanced permeability and retention effect. The presence of
      the SUPR effect after NIR-PIT has prompted regimens in which there is a repeat
      exposure of NIR light 24 hours after the initial NIR-PIT to take advantage of the
      leakage of additional APC deeper into the tumor. However, this post-treatment APC
      penetration was fully induced within 3 hours, therefore, it is possible that
      repeated exposures of NIR light could be administered much earlier than 24 hours
      and still produce the same effects. To test this idea, we compared several modes
      of delivering additional doses of light after initial NIR-PIT. We found that
      repeated exposures of NIR light starting 3 hours after initial NIR-PIT produced
      equal or superior results to more delayed exposures of NIR light. This finding
      has practical implications of an easy-to-perform regimen as repeated light
      exposures could be performed during a single day rather than extending the
      procedure over two days which is the current recommendation.

PMID- 28456785
TI  - Targeted next generation sequencing identified novel mutations in RPGRIP1
      associated with both retinitis pigmentosa and Leber's congenital amaurosis in
      unrelated Chinese patients.
AB  - As the most common inherited retinal degenerations, retinitis pigmentosa (RP) is
      clinically and genetically heterogeneous. Some of the RP genes are also
      associated with other retinal diseases, such as LCA (Leber's congenital
      amaurosis) and CORD (cone-rod dystrophy). Here, in our molecular diagnosis of 99
      Chinese RP patients using targeted gene capture sequencing, three probands were
      found to carry mutations of RPGRIP1, which was known to be associated with
      pathogenesis of LCA and CORD. By further clinical analysis, two probands were
      confirmed to be RP patients and one was confirmed to be LCA patient. These novel
      mutations were co-segregated with the disease phenotype in their families. Our
      result not only expands the mutational spectrum of the RPGRIP1 gene but also
      gives supports to clinical diagnosis and molecular treatment of RP patients.

PMID- 28456786
TI  - Apoptosis-related microRNA-145-5p enhances the effects of pheophorbide a-based
      photodynamic therapy in oral cancer.
AB  - MicroRNAs (miRNAs) regulate key biological processes, and their aberrant
      expression has been related to cancer development. Photodynamic therapy (PDT) has
      emerged as one of the most promising modalities for cancer treatment. However,
      the application of PDT has been limited to superficially localized human
      cancerous and precancerous lesions. To increase the usefulness of both PDT and
      miRNAs in cancer therapy, this study investigated whether apoptosis-related miRNA
      expression is influenced by PDT in oral cancer and whether miRNAs can enhance PDT
      efficacy. To achieve this goal, we performed a miRNA array-based comparison of
      apoptosis-related miRNA expression patterns following PDT using pheophorbide a
      (Pa) as a photosensitizer. After Pa-PDT, 13.1% of the miRNAs were down-regulated,
      and 16.7% of the miRNAs were up-regulated. Representative miRNAs were selected
      according to expression difference: miR-9-5p, miR-32-5p, miR-143-3p, miR-145-5p,
      miR-192-5p, miR-193a-5p, miR-204-5p, miR-212-3p, miR-338-3p, and miR-451a. Among
      them, only miR-145-5p showed the consistent reduction repeatedly in all cell
      lines after Pa-PDT. Further, the combined treatment of a miR-145-5p mimic and Pa
      PDT increased phototoxicity, reactive oxygen species generation, and apoptotic
      cell death, suggesting that miRNAs expression could be a useful marker for
      enhancing the therapeutic effect of Pa-PDT. This study will provide a promising
      strategy for introducing miRNA as cancer therapy.

PMID- 28456787
TI  - Predictive blood plasma biomarkers for EGFR inhibitor-induced skin rash.
AB  - Epidermal growth factor receptor overexpression in human cancer can be
      effectively targeted by drugs acting as specific inhibitors of the receptor, like
      erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a
      typical papulopustular acneiform rash, whose occurrence and severity are
      positively correlated with overall survival in several cancer types. We studied
      molecules involved in epidermal growth factor receptor signaling which are
      quantifiable in plasma, with the aim of identifying biomarkers for the severity
      of rash. With a predictive value for the rash these biomarkers may also have a
      prognostic value for survival and disease outcome.The concentrations of
      amphiregulin, hepatocyte growth factor (HGF) and calcidiol were determined by
      specific enzyme-linked immunosorbent assays in plasma samples from 211
      patients.We observed a significant inverse correlation between the plasma
      concentration of HGF and overall survival in patients with an inhibitor-induced
      rash (p-value = 0.0075; mean overall survival low HGF: 299 days, high HGF: 240
      days) but not in patients without rash. The concentration of HGF was also
      significantly inversely correlated with severity of rash (p-value = 0.00124).High
      levels of HGF lead to increased signaling via its receptor MET, which can
      activate numerous pathways which are normally also activated by epidermal growth
      factor receptor. Increased HGF/MET signaling might compensate the inhibitory
      effect of epidermal growth factor receptor inhibitors in skin as well as tumor
      cells, leading to less severe skin rash and decreased efficacy of the anti-tumor
      therapy, rendering the plasma concentration of HGF a candidate for predictive
      biomarkers.

PMID- 28456788
TI  - A prognostic nomogram for overall survival after neoadjuvant radiotherapy or
      chemoradiotherapy in thoracic esophageal squamous cell carcinoma: a retrospective
      analysis.
AB  - BACKGROUND: Currently, the AJCC staging system or pathological complete response
      (pCR) are considered not sufficiently accurate to evaluate the survival of
      patients with esophageal squamous cell carcinoma after neoadjuvant radiotherapy
      or chemoradiotherapy. This study aimed to establish a nomogram and a recursive
      partitioning analysis (RPA) model to estimate prognosis and to provide advice for
      subsequent treatments. METHODS: We analyzed retrospectively 407 patients that
      were diagnosed with thoracic esophageal squamous cell carcinoma (TESCC) and
      received neoadjuvant radiotherapy or chemoradiotherapy. Hazard ratios and 95%
      confidence intervals of categorical clinicopathological characteristics with
      overall survival (OS) were calculated using the Cox proportional hazard model.
      The nomogram and RPA model were then established and total scores according to
      each variable were calculated and stratified to predict OS. RESULTS: Patients
      were followed-up over a median 49.9 months. AJCC did not perform well in
      distinguishing OS among each stage except for IIB and IIIA. Patients were divided
      into 4 groups according to the total scores based on nomogram (low risk: <=180;
      intermediate risk: 180-270; high risk: 270-340; very high risk: >340). The 5-year
      OS was 57.3%, 40.7%, 18.3%, 6.1% respectively (p<0.05). RPA model also divide the
      patients into 4 groups, though group2 and group3 were not statistically
      significant (p=0.574). CONCLUSION: The nomogram is a good evaluation model for
      estimating the prognosis of patients with TESCC after neoadjuvant radiotherapy or
      chemoradiotherapy compared with the AJCC and RPA. The results of this study also
      suggested that the high-risk subgroups need further treatments.

PMID- 28456789
TI  - Metformin and lung cancer risk in patients with type 2 diabetes mellitus.
AB  - This study evaluated whether metformin might reduce lung cancer risk. The
      reimbursement database of the Taiwan's National Health Insurance was used. A
      sample of 15414 never users and 280159 ever users of metformin (original sample)
      and a 1:1 matched-pairs of ever and never users (n=15414 in each group, matched
      sample) were recruited from patients with newly diagnosed type 2 diabetes
      mellitus during 1999-2005. They were followed until December 31, 2011. Cox
      regression incorporated with the inverse probability of treatment weighting using
      propensity score was used to estimate hazard ratios. Results showed that the
      respective incidence of lung cancer in ever and never users was 173.36 and 292.65
      per 100000 person-years in the original sample; and was 211.71 and 292.65,
      respectively, in the matched sample. The overall hazard ratios (95% confidence
      intervals) of 0.586 (0.509-0.674) in the original sample and 0.717 (0.584-0.881)
      in the matched sample suggested a significantly lower risk among metformin users.
      Hazard ratios comparing the first (<22.60 months), second (22.60-46.67 months)
      and third (>46.67 months) tertile of cumulative duration of metformin use to
      never users was 1.163 (1.005-1.348), 0.612 (0.526-0.711) and 0.176 (0.148-0.210),
      respectively, in the original sample; and was 1.465 (1.131-1.897), 0.758 (0.566
      1.016) and 0.228 (1.460-0.357) in the respective tertile of the matched sample.
      Sensitivity analyses after excluding patients with certain risk factors of cancer
      and subgroup analyses supported a favorable effect of metformin. In
      conclusion,metformin use may reduce lung cancer risk in patients with type 2
      diabetes mellitus.

PMID- 28456790
TI  - Serological proteome analysis approach-based identification of ENO1 as a tumor
      associated antigen and its autoantibody could enhance the sensitivity of CEA and
      CYFRA 21-1 in the detection of non-small cell lung cancer.
AB  - PURPOSE: Lung cancer (LC) is the leading cause of cancer-related deaths for both
      male and female worldwide. Early detection of LC could improve five-year survival
      rate up to 48.8% compared to 3.3% of late/distant stage. Autoantibodies to tumor
      associated antigens (TAAs) have been described as being present before clinical
      symptoms in lung and other cancers. We aimed to identify more TAAs to improve the
      performance for discovering non-small cell lung cancer (NSCLC) patients from
      healthy individuals. METHODS: Two independent sets were included in this study.
      Serological proteome analysis (SERPA) was used to identify TAAs from NSCLC cell
      line H1299 in a discovery set. In validation study, anti-ENO1 autoantibody was
      examined by immunoassay in sera from 242 patients with NSCLC and 270 normal
      individuals. RESULTS: A 47 KDa protein was identified to be alpha-enolase (ENO1)
      by using SERPA. Analysis of sera from 512 participants by ELISA showed
      significantly higher frequency of anti-ENO1 autoantibodies in NSCLC sera compared
      with the sera from normal individuals, with AUC (95%CI) of 0.589 (0.539-0.638,
      P=0.001). There was no significant difference in frequency of anti-ENO1 in
      different stages, histological or metastasis status of NSCLC. When anti-ENO1
      detection was combined with other two tumor protein biomarkers (CEA and CYFRA 21
      1), the sensitivity of NSCLC increased to 84%. CONCLUSIONS: ENO1 can elicit
      humoral immune response in NSCLC and its autoantibody has association with the
      tumorigenesis of NSCLC. Furthermore, these intriguing results suggest the
      possibility of autoantibody against ENO1 serving as a potential diagnostic
      biomarker in NSCLC and have implications for defining novel histological
      determinants of NSCLC.

PMID- 28456792
TI  - Implications of CHA2DS2-VASc Score in Stroke Patients with Atrial Fibrillation:
      An Analysis of 938 Korean Patients.
AB  - BACKGROUND AND AIMS: The aim of this study was to investigate the stroke
      mechanisms and associated conditions influencing the decision regarding stroke
      thromboprophylaxis in patients with atrial fibrillation (AF) plus ischemic
      stroke, according to the CHA2DS2-VASc score. METHODS: We evaluated 938
      consecutive patients with a diagnosis of AF plus transient ischemic
      attack/ischemic stroke. Based on the CHA2DS2-VASc scores, patients were
      stratified as score 0 or 1 (n = 151), score 2 (n = 146), score 3 (n = 213), score
      4 (n = 185), or score >=5 (n = 243). RESULTS: Patients with a higher CHA2DS2-VASc
      score were more likely to have noncardioembolic stroke mechanism (p = 0.001).
      Large-artery atherosclerosis causing stenosis >50% was more frequently observed
      in the high CHA2DS2-VASc group (p < 0.001). Coronary artery disease and the use
      of antiplatelet agents were more prevalent in the higher group (p < 0.001). A
      high CHA2DS2-VASc score was associated with a higher frequency of cerebral
      microbleeds and a higher Fazekas grade for leukoaraiosis (p < 0.001). The HAS
      BLED score was correlated with the CHA2DS2-VASc score (gamma = 0.650; p < 0.001).
      CONCLUSIONS: A higher CHA2DS2-VASc score is associated with noncardioembolic
      mechanisms of stroke and with a higher risk of bleeding. Strategies to treat
      macro/microangiopathy such as use of statin for plaque stabilization, as well as
      oral anticoagulants with a lower bleeding risk, are needed in these patients.

PMID- 28456791
TI  - NK cells and multiple myeloma-associated endothelial cells: molecular
      interactions and influence of IL-27.
AB  - Angiogenesis represents a hallmark of tumor progression in Multiple Myeloma (MM),
      a still incurable malignancy. Here we analyzed the activity of cytokine
      stimulated NK cells against tumor-associated endothelial cells isolated from bone
      marrow aspirates of MM patients with active disease (MMECs). We show that NK
      cells activated with optimal doses of IL-15 killed MMECs thanks to the concerted
      action of multiple activating receptors. In particular, according to the high
      expression of PVR and Nectin-2 on MMECs, DNAM-1 actively participated in target
      recognition. Interestingly, in MMECs the surface density of PVR was significantly
      higher than that detected in endothelium from patients with MM in complete
      remission or with monoclonal gammopathy of undetermined significance (MGUS).
      Importantly, IL-27, which unlike IL-15 does not display pro-angiogenic
      properties, maintained or increased the NK cell functions induced by suboptimal
      concentrations of IL-15. NK cell properties included killing of MMECs, IFN-gamma
      production as well as a peculiar increase of NKp46 expression on NK cell surface.
      Finally, IL-27 showed a striking capability of up-regulating the expression of PD
      L2 and HLA-I on tumor endothelium, whereas it did not modify that of PD-L1 and
      HLA-II.Our results suggest that cytokine-activated endogenous or adoptively
      transferred NK cells might support conventional therapies improving the outcome
      of MM patients.

PMID- 28456793
TI  - Inhibition of Colon Carcinoma Cell Migration Following Treatment with Purified
      Venom from Lesser Weever Fish (Trachinus Vipera).
AB  - BACKGROUND: Injury by the sting of Lesser weever fish (Trachinus vipera) may lead
      to severe pain, edema or tissue necrosis. Cellular effects of the venom are still
      incompletely understood. Previous observations revealed that purified Lesser
      weever fish venom (LWFV) induces suicidal death of erythrocytes and HCT116 human
      colon carcinoma cells. The present study addressed the effect of the venom on
      colon carcinoma cell toxicity, shape and migration both in p53+/+ and/or p53-/-
      conditions. METHODS: Cells were exposed to medium without or with 500 ug/ ml
      LWFV. Cell shape, cell area and circularity were visualized and quantified by
      fluorescence microscopy. Cell volume, granularity and cells toxicity were
      assessed via the apoptotic parameters dissipation of mitochondrial inner
      transmembrane potential, phosphatidylserine surface exposure and cell membrane
      permeabilization were measured utilizing flow cytometry. Cell migration was
      evaluated using wound healing assay and two-dimensional migration assay. RESULTS:
      LWFV treatment was followed by a marked change of cell shape and size,
      significant decrease of cell area and circularity, significant impairment of cell
      migration, as well as induction of apoptosis after long exposition. CONCLUSIONS:
      LWFV exposure leads to cell shrinkage, increased granularity, apoptosis and
      impairment of cell migration, effects presumably contributing to LWFV-induced
      tissue injury.

PMID- 28456794
TI  - Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by
      Artemisinin in Pituitary Tumor (GH3) Cells.
AB  - BACKGROUND: Artemisinin (ART) is an anti-malarial agent reported to influence
      endocrine function. METHODS: Effects of ART on ionic currents and action
      potentials (APs) in pituitary tumor (GH3) cells were evaluated by patch clamp
      techniques. RESULTS: ART inhibited the amplitude of delayed-rectifier K+ current
      (IK(DR)) in response to membrane depolarization and accelerated the process of
      current inactivation. It exerted an inhibitory effect on IK(DR) with an IC50
      value of 11.2 uM and enhanced IK(DR) inactivation with a KD value of 14.7 uM. The
      steady-state inactivation curve of IK(DR) was shifted to hyperpolarization by 10
      mV. Pretreatment of chlorotoxin (1 uM) or iloprost (100 nM) did not alter the
      magnitude of ART-induced inhibition of IK(DR) in GH3 cells. ART also decreased
      the peak amplitude of voltage-gated Na+ current (INa) with a concentration
      dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of
      late INa, was effective at reversing ART-induced prolongation in inactivation
      time constant of INa. Under current-clamp recordings, ART alone reduced the
      amplitude of APs and prolonged the duration of APs. CONCLUSION: Under ART
      exposure, the inhibitory actions on both IK(DR) and INa could be a potential
      mechanisms through which this drug influences membrane excitability of endocrine
      or neuroendocrine cells appearing in vivo.

PMID- 28456795
TI  - Sex-Related Allergic Rhinitis Prevalence Switch from Childhood to Adulthood: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: A sex-related switch in the prevalence of asthma from childhood (male
      predominance) to adulthood (female predominance) has been described, but for
      allergic rhinitis this remains unclear. We aimed to examine sex- and age-group
      specific differences in allergic rhinitis prevalence by systematically evaluating
      studies from across the globe. METHODS: A systematic search of MEDLINE and Embase
      for population-based cross-sectional studies was performed regardless of the
      language of publication. The search was restricted to the present millennium
      (2000 to June 2014). Study quality was defined by the sampling method, response
      rate, sample size, and data collection method. To assess sex differences in the
      prevalence of self- or parent-reported symptoms of rhinitis, calculated pooled
      estimates of the male-female ratio (MFR) were obtained using random-effects model
      meta-analyses due to heterogeneity. A meta-regression analysis was also
      performed. RESULTS: Out of 6,539 publications identified, 67 cross-sectional
      population-based studies (291,726 males and 301,781 females) were included in our
      meta-analysis. In children (<11 years of age) significantly more boys than girls
      had rhinitis symptoms (MFR 1.21, 95% CI 1.17-1.25), whereas in adolescents (11 to
      <18 years of age) males were significantly less often affected than females (MFR
      0.90, 95% CI 0.85-0.95). No sex-specific prevalence difference was observed in
      adults (MFR 0.96, 95% CI 0.83-1.17). These findings were consistent in all
      continents except in Asia, where the male predominance remained beyond childhood.
      CONCLUSIONS: The male predominance of rhinitis prevalence in childhood changed
      towards a female predominance in adolescence across the globe, except in Asia.
      Longitudinal studies are needed to confirm these cross-sectional data and examine
      possible determinants and underlying mechanisms.

PMID- 28456796
TI  - Alpha1-ACT Functions as a Tumour Suppressor in Hepatocellular Carcinoma by
      Inhibiting the PI3K/AKT/mTOR Signalling Pathway via Activation of PTEN.
AB  - BACKGROUND & AIMS: To investigate the expression and prognostic value of alpha1
      ACT (Alpha1-antichymotrypsin) in patients with HCC (hepatocellular carcinoma) and
      identify the mechanism by which alpha1-ACT inhibits proliferation and promotes
      apoptosis of HCC. METHODS: We first measured alpha1-ACT expression levels and
      determined their relationship with the clinicopathological characteristics and
      prognosis of patients with HCC.We then established stable HCC cell lines with
      both alpha1-ACT overexpression and knockdown and performed a functional analysis
      in vitro.We first examined the relationship between alpha1-ACT and the
      PTEN/PI3K/AKT/mTOR pathway using Western blotting. Then, we determined whether
      alpha1-ACT can directly bind to PTEN using co-immunoprecipitation. Finally, we
      measured alpha1-ACT expression to evaluate its correlation with the PI3K/AKT/mTOR
      pathway-related apoptosis proteins in a xenograft tumour mouse model using
      immunohistochemistry. RESULTS: The alpha1-ACT expression level was significantly
      lower in the HCC tissues than in the paratumour tissues and was negatively
      positively correlated with the level of Ki67, AFP, the AJCC stage, tumour size
      and tumour invasion. The overexpression of alpha1-ACT can inhibit cell
      proliferation and increase cell apoptosis by activating PI3K/AKT/mTOR-mediated
      apoptosis via binding to PTEN and activating it in vitro. Additionally, the
      overexpression of alpha1-ACT can also increase the proportion of cells in the
      G0/G1 stage by increasing cyclin p21 expression and inhibiting the migration and
      invasion abilities of HCC cells by regulating MMP2 and MMP9. The
      xenotransplantation studies with nude mice also showed that overexpression of
      alpha1-ACT inhibited tumourigenesis and knockdown of alpha1-ACT had the opposite
      effect. CONCLUSIONS: Our study demonstrates that alpha1-ACT suppresses liver
      cancer development and metastasis via targeting the PTEN/PI3K/AKT/mTOR signalling
      pathway, which may be a potential target for therapeutic intervention in HCC.

PMID- 28456797
TI  - Identification of Two Additional Susceptibility Loci for Inflammatory Bowel
      Disease in a Chinese Population.
AB  - BACKGROUND/AIMS: To investigate the associations between the rs1250569 (zinc
      finger MIZ-type containing 1, ZMIZ1), rs1042522 (tumour protein p53, TP53), and
      rs10114470 (tumour necrosis factor-like cytokine 1A, TL1A) polymorphisms and the
      development of inflammatory bowel disease (IBD) in a Chinese (Han) population. We
      analysed the expression of genes that predispose patients to Crohn's disease (CD)
      and ulcerative colitis (UC). METHODS: A total of 381 IBD patients and 517 healthy
      controls were recruited into our study. Polymorphisms at the three loci were
      genotyped using polymerase chain reaction-ligation detection reactions (PCR-LDR).
      Genotype-phenotype correlations were analysed. Blood and gut samples were
      obtained and analysed using quantitative real-time PCR (qRT-PCR), western blot
      analysis, and immunohistochemistry to investigate the mRNA and protein levels and
      in situ expression of genes found to predispose patients to IBD. Furthermore, the
      expression of susceptible genes was further verified using a mouse dextran
      sulphate sodium (DSS)-induced acute colitis model. RESULTS: No significant
      association was detected between rs1250569 and rs1042522 genotypes and CD or UC
      susceptibility. However, the frequency of allele A of rs1250569 was much higher
      in CD patients than that in healthy controls (55.03% vs. 48.48%, respectively; p
      = 0.044). The mutation rates at rs10114470 were dramatically lower at both the
      genotype and allele level in patients than those in healthy controls (p = 0.002
      at both the genotype and allele level). Additionally, increased ZMIZ1 and TL1A
      levels were detected in intestinal samples obtained from both IBD patients and
      DSS-treated mice. CONCLUSION: rs1250569 (ZMIZ1) and rs10114470 (TL1A) are two
      novel loci that indicate susceptibility to IBD in Han-Chinese patients.
      Consistent with previous studies, TL1A expression levels were higher in Chinese
      Han IBD patients and DSS-treated mice. Most importantly, we found that ZMIZ1
      expression was markedly higher in both IBD patients and mice with experimentally
      induced colitis, suggesting that ZMIZ1 plays important roles in the pathogenesis
      of IBD.

PMID- 28456798
TI  - Malpositioning of a Tunneled Hemodialysis Catheter into the Azygos Vein: A Case
      Report and Literature Review.

PMID- 28456799
TI  - Allicin Decreases Lipopolysaccharide-Induced Oxidative Stress and Inflammation in
      Human Umbilical Vein Endothelial Cells through Suppression of Mitochondrial
      Dysfunction and Activation of Nrf2.
AB  - BACKGROUND: Allicin, a major component of garlic, is regarded as a
      cardioprotective agent and is associated with increased endothelial function.
      METHODS: The effects of allicin on lipopolysaccharide (LPS)-induced vascular
      oxidative stress and inflammation in cultured human umbilical vein endothelial
      cells (HUVECs) and the mechanisms underlying these effects were studied. The
      protective effects were measured using cell viability, a lactate dehydrogenase
      (LDH) assay and cell apoptosis as indicators, and the anti-oxidative activity was
      determined by measuring reactive oxygen species (ROS) generation, oxidative
      products and endogenous antioxidant enzyme activities. HUVEC mitochondrial
      function was assessed by determining mitochondrial membrane potential (MMP)
      collapse, cytochrome c production and mitochondrial ATP release. To investigate
      the potential underlying mechanisms, we also measured the expression of dynamic
      mitochondrial proteins using western blotting. Furthermore, we evaluated the Nrf2
      antioxidant signaling pathway using an enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Our results demonstrated that allicin enhanced HUVEC proliferation,
      which was suppressed by LPS exposure, and LDH release. Allicin ameliorated LPS
      induced apoptosis, suppressed ROS overproduction, reduced lipid peroxidation and
      decreased the endogenous antioxidant enzyme activities in HUVECs. These
      protective effects were associated with the inhibition of mitochondrial
      dysfunction as indicated by decreases in the MMP collapse, cytochrome c synthesis
      and mitochondrial ATP release. In addition, allicin attenuated the LPS-induced
      inflammatory responses, including endothelial cell adhesion and TNF-alpha and IL
      8 production. Furthermore, allicin increased the expression of LXRalpha in a dose
      dependent manner. Allicin-induced attenuation of inflammation was inhibited by
      LXRalpha siRNA treatment. Finally, allicin activated NF-E2-related factor 2
      (Nrf2), which controls the defense against oxidative stress and inflammation.
      CONCLUSIONS: Taken together, the present data suggest that allicin attenuated the
      LPS-induced vascular injury process, which may be closely related to the
      oxidative stress and inflammatory response in HUVECs. Allicin modulated Nrf2
      activation and protected the cells against LPS-induced vascular injury. Our
      findings suggest that allicin attenuated the LPS-induced inflammatory response in
      blood vessels.

PMID- 28456800
TI  - Inhaled Glucocorticoids and Pneumonia in Preterm Infants: Post Hoc Results from
      the NEuroSIS Trial.
AB  - BACKGROUND: Inhaled glucocorticoids may increase the risk of pneumonia in adults.
      Thus, respiratory infections may be a potential explanation for the non
      significantly increased mortality seen in the glucocorticoid group in the largest
      randomized trial on inhaled glucocorticoids for preventing bronchopulmonary
      dysplasia in preterm infants published to date (NEuroSIS). OBJECTIVE: To evaluate
      the effect of inhaled budesonide on the risk of death due to respiratory
      infections in the NEuroSIS trial. METHODS: We performed post hoc analyses of
      prospectively collected data from 856 preterm infants on presumed but not culture
      proven sepsis and antimicrobial drug use. Additionally, pulmonary complications
      reported on adverse event forms, death certificates and autopsy reports were
      compared between study groups. RESULTS: Treatment groups did not differ in the
      number of episodes with suspected sepsis (184/437 [42.1%] in the budesonide vs.
      171/419 [40.8%] in the placebo group). Neither the number of patients receiving
      antimicrobial drugs nor the length of antimicrobial treatment differed between
      groups. Our analyses for pulmonary adverse events as well as for pulmonary
      complications reported on death certificates and autopsy reports did not suggest
      a negative impact of inhaled budesonide on these outcomes. CONCLUSION: The
      current analysis does not support the assumption that respiratory tract
      infections explain the increased mortality seen in the glucocorticoid group in
      the NEuroSIS trial.

PMID- 28456801
TI  - Variability in Ultrasound Measurement of Hyoid Bone Displacement and Submental
      Muscle Size Using 2 Methods of Data Acquisition.
AB  - OBJECTIVE: This study compares variability in measures of hyoid bone displacement
      and submental muscle size using 2 methods of ultrasound transducer placement:
      fixed and hand-held. PATIENTS AND METHODS: Twenty-four healthy participants (11
      males, 13 females) aged between 51 and 84 years were scanned using both methods.
      Repeated measures were collected within and across 3 sessions. RESULTS: A
      nonlinear mixed effects model was used to estimate the effects of the method,
      trial, and session. The fixed transducer produced greater within- and across
      session variability on several measures compared to the hand-held method. Fixed
      transducer measurements of hyoid bone displacement were 9.4% smaller compared to
      hand-held measurements (F[1, 24.34] = 3.58, p = 0.07). CONCLUSION: Results
      suggest that using a fixed transducer does not necessarily improve measurement
      accuracy of swallowing outcomes in a healthy system. The wide variability in
      individual measures indicates that further research is required before ultrasound
      is used for outcome measurement in rehabilitation.

PMID- 28456802
TI  - Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-kappaB and MAPK
      Signaling Pathways.
AB  - BACKGROUND/AIMS: This study aimed to investigate the anti-inflammatory activity
      of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis
      amurensis (Xiao Bo An), and the underlying mechanisms. METHODS: Macrophages and
      neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The
      effects of BER on the expression of pro-inflammatory mediators in macrophages
      were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the
      activation and superoxide release of neutrophils were determined with flow
      cytometry and WST-1 reduction test. The inhibitory effects of BER on the
      activation of signaling pathways related to inflammatory response in macrophages
      were evaluated by western blot analysis. In addition, a mouse peritonitis model
      was made by peritoneal injection of thioglycollate medium and anti-inflammatory
      effects of BER were investigated in vivo by quantitative analysis of pro
      inflammatory factor production and leukocyte exudation. RESULTS: BER
      significantly inhibited inflammatory factor expression by LPS-stimulated
      macrophages and suppressed activation and superoxide release of fMLP-stimulated
      neutrophils. In the mouse peritonitis model, BER significantly inhibited the
      activation of macrophages and exudation of neutrophils. According to analysis,
      BER significantly suppressed phosphorylation of NF-kappaB and MAPK (JNK and
      ERK1/2) signaling pathways in LPS-stimulated macrophages. CONCLUSIONS:
      Collectively, data from this study suggest that BER has anti-inflammatory
      potential, which is effected via inhibition of NF-kappaB and MAPK signaling
      pathways, and thus holds promise for treatment of inflammatory disease.

PMID- 28456803
TI  - Expression and Characterization of Serotype 2 Streptococcus suis Arginine
      Deiminase.
AB  - BACKGROUND: Arginine deiminase (ArcA) has been speculated to facilitate the
      intracellular survival of Streptococcus suis under acidic conditions. However,
      the physical and biological properties and function of SS2-ArcA have not yet been
      elucidated. METHODS: Recombinant SS2-ArcA (rSS2-ArcA) was expressed and purified
      using Ni-NTA affinity chromatography. Under various pH and temperature
      conditions, the enzymatic properties of purified rSS2-ArcA and crude native SS2
      ArcA were determined. RESULTS: The SS2-arcA-deduced amino acid sequence contained
      a conserved catalytic triad (Cys399-His273-Glu218). The optimum temperature and
      pH of 47-kDa rSS2-ArcA and crude native SS2-ArcA were 42 degrees C and pH 7.2.
      The rSS2-ArcA and crude native SS2-ArcA were stable for 3 h at 4 and 25 degrees
      C, respectively. The pH stability and dependency tests suggested that rSS2-ArcA
      and crude native SS2-ArcA were functionally active in acidic conditions. The L
      arginine substrate binding affinity (Km) values of rSS2-ArcA (specific activity
      16.00 U/mg) and crude native SS2-ArcA (specific activity 0.23 U/mg) were 0.058
      and 0.157 mM, respectively. rSS2-ArcA exhibited a weak binding affinity with the
      common ArcA inhibitors L-canavanine and L-NIO. Furthermore, the partial
      inactivation of SS2-ArcA significantly impaired the viability and growth of SS2
      at pH 4.0, 6.0, and 7.5. CONCLUSIONS: This study profoundly demonstrated the
      involvement of ArcA enzymatic activity in S. suis survival under acidic
      conditions.

PMID- 28456804
TI  - Climate and Allergic Sensitization to Airborne Allergens in the General
      Population: Data from the French Six Cities Study.
AB  - BACKGROUND: The results of international epidemiological surveys show large
      geographical variations in skin test reactivity but do not provide a rationale
      for such variations. OBJECTIVE: To assess the relationship between climate and
      allergic sensitization in schoolchildren. METHODS: In the present study, we
      analyzed data from a multicenter, epidemiological survey that included 6,461
      schoolchildren, aged 9-11 years, living in 6 French cities scattered around
      France. The protocol also included a battery of skin prick tests to common
      airborne allergens. The crude prevalence of sensitization to each allergen was
      estimated for each city and then adjusted for potential confounding factors. This
      analysis was repeated for monosensitization and for allergens grouped into 2
      categories: indoor allergens, i.e., house dust mite (HDM), cat, and cockroach
      allergens, and outdoor allergens, i.e., birch pollen, grass pollen, and
      Alternaria. We also grouped cities according to their location on the coast,
      i.e., Marseille and Bordeaux, or inland, i.e., Creteil, Clermont-Ferrand, Reims,
      and Strasbourg. RESULTS: A difference in prevalence of sensitization to each
      airborne allergen or allergens grouped into indoor and outdoor categories was
      found between cities, even after adjusting for potential confounding factors.
      Also, a higher prevalence of sensitization to HDM, cat dander, and, broadly
      speaking, indoor allergens, was found in children living on the coast than in
      those living inland, whereas they showed a lower prevalence of sensitization to
      birch pollen. Between-city differences in the prevalence of monosensitization
      were also statistically significant. Children living in coastal cities had a
      higher rate of monosensitization to indoor allergens and a lower prevalence of
      sensitization to birch pollen. The higher prevalence of allergic sensitization in
      children from coastal cities is most likely due to climatic conditions, such as
      proximity from sea and humidity. Differences in sensitization to birch allergens
      could be due to differential exposure to these pollen. CONCLUSION: These results
      indicate a role of environmental exposure in sensitization to perennial as well
      as seasonal allergens.

PMID- 28456806
TI  - Navigating through the Jungle of Allergens: Features and Applications of Allergen
      Databases.
AB  - The increasing number of available data on allergenic proteins demanded the
      establishment of structured, freely accessible allergen databases. In this review
      article, features and applications of 6 of the most widely used allergen
      databases are discussed. The WHO/IUIS Allergen Nomenclature Database is the
      official resource of allergen designations. Allergome is the most comprehensive
      collection of data on allergens and allergen sources. AllergenOnline is aimed at
      providing a peer-reviewed database of allergen sequences for prediction of
      allergenicity of proteins, such as those planned to be inserted into genetically
      modified crops. The Structural Database of Allergenic Proteins (SDAP) provides a
      database of allergen sequences, structures, and epitopes linked to bioinformatics
      tools for sequence analysis and comparison. The Immune Epitope Database (IEDB) is
      the largest repository of T-cell, B-cell, and major histocompatibility complex
      protein epitopes including epitopes of allergens. AllFam classifies allergens
      into families of evolutionarily related proteins using definitions from the Pfam
      protein family database. These databases contain mostly overlapping data, but
      also show differences in terms of their targeted users, the criteria for
      including allergens, data shown for each allergen, and the availability of
      bioinformatics tools.

PMID- 28456805
TI  - Allergens of Blomia tropicalis: An Overview of Recombinant Molecules.
AB  - Allergic diseases are considered a major problem for healthcare systems in both
      developed and developing countries. House dust mites are well-known triggers of
      allergic manifestations. While the Dermatophagoides genus is widely distributed
      globally, Blomia tropicalis is the most prominent mite species in the tropical
      and subtropical regions of the world. Over the last decades, an increase in
      sensitization rates to B. tropicalis has been reported, leading to increased
      research efforts on Blomia allergens. In fact, 8 new allergens have been
      identified and characterized to different degrees. Here, we provide an overview
      of recent developments concerning the identification and production of
      recombinant Blomia allergens, as well as their structural and immunological
      characterization. Although considerable progress has been achieved, detailed
      molecule-based studies are still needed to better define the clinical relevance
      of Blomia allergens. Thus, the establishment of a well-standardized and fully
      characterized panel of allergens remains a challenge for the development of
      better diagnosis and therapy of allergic diseases induced by B. tropicalis.

PMID- 28456807
TI  - Prevalence of Major Comorbidities in Chronic Obstructive Pulmonary Disease Caused
      by Biomass Smoke or Tobacco.
AB  - BACKGROUND: Comorbidities are very common in chronic obstructive pulmonary
      disease (COPD), contributing to the overall severity of the disease. The relative
      prevalence of comorbidities in COPD caused by biomass smoke (B-COPD), compared
      with COPD related to tobacco (T-COPD), is not well known. OBJECTIVES: To
      establish if both types of COPD are associated with a different risk for several
      major comorbidities. METHOD: The prevalence of comorbidities was compared in 863
      subjects with B-COPD (n = 179, 20.7%) or T-COPD (n = 684, 79.2%). Multivariate
      analysis was carried out to explore the independent relationship between
      comorbidities and type of exposure. RESULTS: Three comorbidities were more
      frequent in T-COPD than in B-COPD: ischemic heart disease (11.5 vs. 5.0%,
      respectively, p = 0.01), peripheral vascular disease (9.2 vs. 2.7%, p = 0.006),
      and peptic ulcer disease (4.8% vs. 0, p = 0.005). After correcting for potential
      confounding variables, the risk of ischemic heart disease was lower in B-COPD
      than in T-COPD (OR: 0.33, 95% CI: 0.16-0.69, p = 0.003). CONCLUSIONS: The
      prevalence of ischemic heart disease is significantly lower in B-COPD than in T
      COPD, suggesting a different systemic effect of both types of smoke in COPD
      patients.

PMID- 28456808
TI  - Heterozygous Nonsense Mutation in the Androgen Receptor Gene Associated with
      Partial Androgen Insensitivity Syndrome in an Individual with 47,XXY Karyotype.
AB  - There are only 2 patients with 47,XXY karyotype and androgen receptor (AR) gene
      mutation reported in the literature, and both are diagnosed as complete androgen
      insensitivity syndrome (CAIS). We report a 22-year-old female with 47,XXY
      karyotype and atypical external genitalia. Sequencing of AR revealed the
      heterozygous p.Asn849Lys*32 mutation, and extensive X chromosome microsatellite
      analysis showed homozygosity for Xp and heterozygosity for Xq, suggesting partial
      X maternal isodisomy. Partial androgen insensitivity syndrome (PAIS) developed in
      this case, probably because of the presence of the heterozygous AR mutation and
      random X- inactivation of the healthy allele. This is the first report of a
      female patient with 47,XXY karyotype and PAIS phenotype.

PMID- 28456809
TI  - Samuel Thomas Soemmerring (1755-1830): The Naming of Cranial Nerves.
AB  - Samuel Thomas Soemmerring was a Prussian polymathic doctor with remarkable
      achievements in anatomy, draftsmanship and inventions. His naming of 12 pairs of
      cranial nerves in his graduation thesis is of particular importance. He also gave
      original descriptions of the macula, sensory pathways and of the substantia
      nigra. His non-medical contributions were diverse and included criticism of the
      guillotine, invention of a telegraphic system, and discoveries in palaeontology.

PMID- 28456812
TI  - Comparison of the Performance of Skin Prick, ImmunoCAP, and ISAC Tests in the
      Diagnosis of Patients with Allergy.
AB  - BACKGROUND: Allergy is diagnosed from typical symptoms, and tests are performed
      to incriminate the suspected precipitant. Skin prick tests (SPTs) are commonly
      performed, inexpensive, and give immediate results. Laboratory tests (ImmunoCAP)
      for serum allergen-specific IgE antibodies are usually performed more
      selectively. The immuno-solid phase allergen chip (ISAC) enables testing for
      specific IgE against multiple allergen components in a multiplex assay. METHODS:
      We retrospectively analysed clinic letters, case notes, and laboratory results of
      118 patients attending the National Adult Allergy Service at the University
      Hospital of Wales who presented diagnostic difficulty, to evaluate which testing
      strategy (SPT, ImmunoCAP, or ISAC) was the most appropriate to use to confirm the
      diagnosis in these complex patients, evaluated in a "real-life" clinical service
      setting. RESULTS: In patients with nut allergy, the detection rates of SPTs (56%)
      and ISAC (65%) were lower than those of ImmunoCAP (71%). ISAC had a higher
      detection rate (88%) than ImmunoCAP (69%) or SPT (33%) in the diagnosis of oral
      allergy syndrome. ImmunoCAP test results identified all 9 patients with
      anaphylaxis due to wheat allergy (100%), whereas ISAC was positive in only 6 of
      these 9 (67%). CONCLUSIONS: In this difficult diagnostic group, the ImmunoCAP
      test should be the preferred single test for possible allergy to nuts, wheat,
      other specific foods, and anaphylaxis of any cause. In these conditions, SPT and
      ISAC tests give comparable results. The most useful single test for oral allergy
      syndrome is ISAC, and SPT should be the preferred test for latex allergy.

PMID- 28456813
TI  - Early Thrombosuction and Tirofiban Use in Knee and Below-Knee Arterial
      Thrombosis.
AB  - BACKGROUND Acute limb ischemia (ALI) is a clinical entity with a high rate of
      morbidity and mortality. Despite advances and variety of its management, there is
      still no criterion standard treatment. The goal of this study was to evaluate the
      effect of tirofiban use on the early and 6-month prognosis of patients with knee
      and below-knee arterial thrombosis who were treated with percutaneous
      thrombosuction (PT) within 24 h. MATERIAL AND METHODS Data of consecutive ALI
      patients who were diagnosed with popliteal and infra-popliteal arterial
      thrombosis and underwent PT procedure within 24 h between January 2010 and
      September 2015 were evaluated retrospectively. Patients were separated into 2
      groups according to tirofiban usage. RESULTS A total of 105 patients (mean age
      67+/-16; 53% men) were included in the study. Atrial fibrillation (n 64, 61%) and
      hypertension (n 60, 57%) were the most frequent comorbidities in patients with
      thromboembolic events. A significantly higher rate of distal embolization (6% vs.
      16%; p=0.01) and slow-flow (17% vs. 30%; p<0.01) developed in patients who were
      not treated with tirofiban after the PT procedure. Although major and minor
      bleeding were more frequent in the tirofiban group, only the rate minor bleeding
      was statistically significant (29% vs. 9%, p=0.001). Reverse embolic event ratio
      was similar in both groups. Although there was a higher rate of amputation in
      patients not treated with tirofiban, the difference was not significant.
      CONCLUSIONS Adding tirofiban to PT reduces angiographic thromboembolic
      complications. Usage of tirofiban in patients prone to thromboembolic events may
      be useful for improving success of the PT procedure, with a reasonable bleeding
      ratio.

PMID- 28456814
TI  - Telescopic Corsair in 5F Guidion for Retrograde Recanalization of Complex Chronic
      Total Occlusions (CTOs).
AB  - BACKGROUND Retrograde advancement of microcatheters through septal/epicardial
      connectors can be challenging. Although several tricks might help to do so (e.g.,
      balloon trap of retro wire in second guiding, balloon trap of retro wire in
      native coronary artery, and use of antegrade extension to approximate the
      antegrade conduit to the retrograde gear), these tricks cannot always be applied,
      especially in patients with poor access. Also, puncturing, knuckling, and
      crossing of the distal CTO cap (or the aorta as described in 1 of the cases)
      sometimes needs a lot of backup of the microcatheter. CASE REPORT We describe 3
      cases in which we used a novel telescopic technique with 5F Guidion (IMDS(r))
      supported retrograde Corsair (Asahi(r)) advancement in complex CTO lesions.
      CONCLUSIONS The telescopic Corsair in 5F Guidion may offer the support needed to
      end successfully in these situations.

PMID- 28456815
TI  - Video-Assisted Anal Fistula Treatment (VAAFT) for Complex Anal Fistula: A
      Preliminary Evaluation in China.
AB  - BACKGROUND Although many attempts have been made to advance the treatment of
      complex anal fistula, it continues to be a difficult surgical problem. This study
      aimed to describe the novel technique of video-assisted anal fistula treatment
      (VAAFT) and our preliminary experiences using VAAFT with patients with complex
      anal fistula. MATERIAL AND METHODS From May 2015 to May 2016, 52 patients with
      complex anal fistula were treated with VAAFT at Yangpu Hospital of Tongji
      University School of Medicine, and the clinical data of these patients were
      reviewed. RESULTS VAAFT was performed successfully in all 52 patients. The median
      operation time was 55 minutes. Internal openings were identified in all cases. 50
      cases were closed with sutures, and 2 were closed with staplers. Complications
      included perianal sepsis in 3 cases and bleeding in another 3 cases. Complete
      healing without recurrence was achieved in 44 patients (84.6%) after 9 months of
      follow-up. No fecal incontinence was observed. Furthermore, a significant
      improvement in Gastrointestinal Quality of Life Index (GIQLI) score was observed
      from preoperative baseline (mean, 85.5) to 3-month follow-up (mean, 105.4;
      p<0.001), and this increase was maintained at 9-months follow-up (mean, 109.6;
      p<0.001). CONCLUSIONS VAAFT is a safe and minimally invasive technique for
      treating complex anal fistula with preservation of anal sphincter function.

PMID- 28456817
TI  - Erratum to: Medial patellofemoral ligament (MPFL) reconstruction in combination
      with a modified grammont technique leads to favorable mid-term results in
      adolescents with recurrent patellofemoral dislocations.

PMID- 28456816
TI  - Early combined arthroscopic treatment for simultaneous ruptures of the patellar
      tendon and the anterior cruciate ligament leads to good radiological results and
      patient satisfaction.
AB  - PURPOSE: Simultaneous rupture of the patellar tendon (PT) and the anterior
      cruciate ligament (ACL) is a relatively rare injury. This study offers a
      comprehensive review of the published reports and presents two cases of
      simultaneous PT and ACL rupture. METHODS: A systematic review of English
      literature was performed, and data from two patients who were referred to our
      institution with simultaneous PT and ACL rupture were collected. Both patients
      underwent primary arthroscopic ACL reconstruction combined with PT reconstruction
      and, 1 year after surgery, magnetic resonance imaging (MRI), clinical
      examination, strength measurement and functional assessment. RESULTS: Fourteen
      studies (24 patients) were included in the review. A two-stage approach was used
      in eight cases (33.3%), and in nine the use of arthroscopy was documented
      (37.5%). Post-operative scores were documented for nine patients (average IKDC
      91.2; Lysholm 94.6), and radiological results were provided for seven. In the two
      newly reported cases, satisfactory functional results were obtained and MRI at 1
      year follow-up revealed regular PT and ACL signal. CONCLUSIONS: No consensus has
      been established for neither a diagnostic nor a therapeutic algorithm for
      simultaneous PT and ACL ruptures. Early combined arthroscopic treatment leads to
      good radiological results, accelerated recovery and patient satisfaction; further
      studies are required to confirm the role of arthroscopy and assess the
      superiority of a specific technique. LEVEL OF EVIDENCE: Review of level IV and V
      studies and case series, Level IV.

PMID- 28456818
TI  - Hepatic segmental atrophy and nodular elastosis: imaging features.
AB  - PURPOSE: To evaluate the imaging features of hepatic segmental atrophy and
      nodular elastosis. MATERIALS AND METHODS: In this Institutional review board
      (IRB)-approved, HIPAA-compliant study, we reviewed imaging features in six cases
      of histologically confirmed hepatic segmental atrophy (HSA) and nodular elastosis
      (NE). Retrospective review of ultrasound (US) in 2 patients, computed tomography
      (CT) in 5 patients, magnetic resonance imaging (MRI) in 4 patients, and positron
      emission tomography (PET) in 2 patients was performed. Location, size, and
      attenuation/density/signal intensity of these lesions were evaluated. Clinical
      presentation and coexistent conditions were also recorded. RESULTS: All six
      patients were females. Mean age of presentation was 58.3 years (range 37-80). A
      single HSA and NE lesion in each patient was found. The mean size of the lesion
      was 18 mm (range: 3 mm to 36 mm). Most lesions were detected incidentally (5/6).
      On contrast-enhanced single-phase (portal venous) CT, most lesions were hypodense
      (4/5) and one lesion was hyperdense to fatty liver parenchyma. On MRI, the
      lesions were iso- to hyperintense on T2-weighted images, T1 hypointense, and
      hyperintense on diffusion-weighted images (DWI). Three lesions were hypointense
      on arterial, portal venous, and delayed phases. One lesion occurring in fatty
      liver appeared hyperintense on all three phases. Gd-EOB-DTPA-enhanced images were
      available in 2 patients and lesions were hypointense on the 20-min hepatobiliary
      phase. On PET, two lesions were isometabolic to the background hepatic
      parenchyma. On ultrasound, one lesion appeared hypoechoic and another lesion
      isoechoic to hepatic parenchyma. CONCLUSIONS: Hepatic segmental atrophy and
      nodular elastosis is an uncommon benign lesion and can simulate metastases due to
      variable imaging features. Lack of FDG uptake on PET/CT may be a clue to the
      benign nature of the lesion and may suggest the possibility of HSA and NE.

PMID- 28456819
TI  - Bidirectional transfer between joint and individual actions in a task of discrete
      force production.
AB  - The present study examined bidirectional learning transfer between joint and
      individual actions involving discrete isometric force production with the right
      index finger. To examine the effects of practice of joint action on performance
      of the individual action, participants performed a pre-test (individual
      condition), practice blocks (joint condition), and a post-test (individual
      condition) (IJI task). To examine the effects of practice of the individual
      action on performance during the joint action, the participants performed a pre
      test (joint condition), practice blocks (individual condition), and a post-test
      (joint condition) (JIJ task). Whereas one participant made pressing movements
      with a target peak force of 10% maximum voluntary contraction (MVC) in the
      individual condition, two participants produced the target force of the sum of
      10% MVC produced by each of them in the joint condition. In both the IJI and JIJ
      tasks, absolute errors and standard deviations of peak force were smaller post
      test than pre-test, indicating bidirectional transfer between individual and
      joint conditions for force accuracy and variability. Although the negative
      correlation between forces produced by two participants (complementary force
      production) became stronger with practice blocks in the IJI task, there was no
      difference between the pre- and post-tests for the negative correlation in the
      JIJ task. In the JIJ task, the decrease in force accuracy and variability during
      the individual action did not facilitate complementary force production during
      the joint action. This indicates that practice performed by two people is
      essential for complementary force production in joint action.

PMID- 28456821
TI  - Use of the Pelvic Organ Quantification System (POP-Q) in published articles of
      peer-reviewed journals.
AB  - INTRODUCTION AND HYPOTHESIS: The Pelvic Organ Quantification (POP-Q) system is a
      standardized technique used for staging POP. This study aimed to examine POP-Q
      use in peer-reviewed publications. METHODS: Nine journals representative of
      urogynecology were reviewed for articles describing POP staging from January to
      December 2012 and 2015. Review articles, editorials, letters and articles with or
      without retractions in manuscript form were excluded. The primary outcome was
      frequency of POP-Q use. Secondary outcomes were POP-Q use by journal specialty,
      specialty of primary author, country of origin, and an anatomic definition of
      failure. Data were evaluated using chi-square tests. Results yielding p < 0.05
      were deemed statistically significant. RESULTS: Two hundred and nineteen articles
      were reviewed. POP-Q was used in 88.4% in 2012 and 80% in 2015(not significant; p
      = 0.296). Urologists used the POP-Q least frequently, although its use was
      greater in 2015 (63.6%) than in 2012 (50%). In 2012, a definition for anatomic
      failure was present in 27% of articles; 23% of authors in the 2012 time frame
      reported using the POP-Q, and 17.8% used a specific POP-Q point. Between 2012 and
      2015, the use of a specific point significantly decreased (17.8 vs. 7.8%, p =
      0.033). CONCLUSION: POP-Q is the most common staging system used in published
      articles across studied subgroups. When used as an outcome measure, a greater
      number of authors use the recommended staging system rather than specific points.

PMID- 28456822
TI  - Response: Amiodarone-induced thyroid dysfunction and a perturbed N-desethyl
      amiodarone to amiodarone ratio; could a drug-induced toxicity be regulating
      exposure to the offending agent?

PMID- 28456823
TI  - A systematic review of interventions to deprescribe benzodiazepines and other
      hypnotics among older people.
AB  - PURPOSE: Benzodiazepines are effective medicines for insomnia and anxiety but are
      commonly used beyond recommended treatment time frames, which may lead to adverse
      drug events. The aim of this systematic review was to critically evaluate the
      success of interventions used to reduce benzodiazepines and 'Z-drug' use, and the
      impact of these interventions on clinical outcomes in older adults. METHODS: A
      search was conducted in PubMed, Embase, Informit, International Pharmaceutical
      Abstracts, Scopus, PsychINFO, Cochrane Central Register of Controlled Trials
      (CENTRAL) and CINAHL. Studies conducted in older adults (>=65 years) and
      published between January 1995 and July 2015 were included. Two authors
      independently reviewed all articles for eligibility and extracted the data.
      RESULTS: Seven studies of benzodiazepines and Z-drug withdrawal were identified.
      Benzodiazepine discontinuation rates were 64.3% in one study that employed
      pharmacological substitution with melatonin and 65.0% in a study that employed
      general practitioner-targeted intervention. Mixed interventions including patient
      education and tapering (n = 2), pharmacological substitution with psychological
      support (n = 1) and tapering with psychological support (n = 1) yielded
      discontinuation rates between 27.0 and 80.0%. Five studies measured clinical
      outcomes following benzodiazepine discontinuation. Most (n = 4) observed no
      difference in prevalence of withdrawal symptoms or sleep quality, while one study
      reported decline in quality of life in those who continued taking benzodiazepine
      vs. those who discontinued over 8 months. CONCLUSIONS: Current evidence shows
      that benzodiazepine withdrawal is feasible in the older population, but
      withdrawal rates vary according to the type of intervention. As the benefits and
      sustainability of these interventions are unclear, further studies should be
      conducted to assess this.

PMID- 28456824
TI  - Identification of Sesbania sesban (L.) Merr. as an Efficient and Well Adapted
      Phytoremediation Tool for Cd Polluted Soils.
AB  - A pot experiment was carried out to assess Cd uptake and accumulation efficiency
      of Sesbania sesban. Plants were grown in soil spiked with 25, 50, 100, 150, 200,
      250, and 300 mg/kg Cd. After 120 days, plants were harvested and analyzed for Cd
      content. A steady increase in Cd accumulation with increasing metal concentration
      in soil was observed for all treatments. Accumulation of Cd was greatest in roots
      (86.7 +/- 6.3 mg/kg), followed by stem (18.59 +/- 1.9 mg/kg), and leaf (3.16 +/-
      1.1 mg/kg). Chlorophyll content declined with increasing Cd concentration, while
      proline and protein content increased as compared to control. At higher Cd
      levels, root, shoot length, and biomass were all significantly reduced (p <=
      0.001). An increase in total protein along with greater A250/A280 value suggested
      an increase in metal-protein complexes. Considering the rapid growth, high
      biomass, accumulation efficiency, and adaptive properties, this plant could be
      used as a valuable tool for the phytoremediation of Cd contaminated soils.

PMID- 28456825
TI  - Expression of angiopoietin-like protein 8 correlates with VEGF in patients with
      proliferative diabetic retinopathy.
AB  - PURPOSE: To investigate the vitreous and serum levels of angiopoietin-like
      protein 8 (ANGPTL-8) and vascular endothelial growth factor (VEGF) in patients
      with proliferative diabetic retinopathy (PDR). The serum levels of these factors
      were also analyzed in patients with diabetes and no diabetic retinopathy (NDR)
      and with non-proliferative diabetic retinopathy (NPDR), to detect the possible
      correlation between the ANGPTL-8 levels and hyperlipidemia. METHODS: Vitreous
      samples were obtained from 28 patients with PDR and from 12 patients without
      diabetes and with idiopathic macular hole (IMH). Serum samples were also obtained
      from 26 patients with NDR and 22 patients with NPDR. ANGPTL-8 levels and other
      factors were determined using an enzyme-linked immunosorbent assay. RESULTS: The
      ANGPTL-8 and VEGF levels in the vitreous and serum of the patients with PDR were
      higher than those in the patients with IMH, and were significantly correlated.
      The vitreous and serum ANGPTL-8 levels were more correlated with the triglyceride
      and low-density lipoprotein cholesterol levels than with the high-density
      lipoprotein cholesterol or total cholesterol levels in the patients with PDR.
      CONCLUSIONS: The vitreous and serum ANGPTL-8 levels were both upregulated in
      patients with PDR. There was an association between the elevation in the ANGPTL-8
      levels and angiogenic and hyperlipidemic factors in the patients with PDR. These
      results suggest that ANGPTL-8 is a potential new diagnostic marker and
      therapeutic target for PDR treatment.

PMID- 28456826
TI  - Comparison of Descemet stripping under continuous air flow, manual air injection
      and balanced salt solution for DMEK: a pilot study.
AB  - BACKGROUND: Descemet's membrane endothelial keratoplasty (DMEK) involves removal
      of the recipient's Descemet membrane (DM) prior to transplanting the donor's DM.
      When using balanced salt solution (BSS) or ophthalmic viscosurgical devices
      (OVDs), visualization of the host's DM during its stripping may be inadequate and
      may result in Descemet remnants and could lead to sub-optimal surgical results.
      Previous articles described excellent visualization when utilizing air injection
      but this requires repeated air injection into the anterior chamber (AC). We
      present a pilot study that compares different techniques under which DM stripping
      can be performed: with continuous automated air infusion, with manual air
      infusion, and with BSS. METHODS: We retrospectively compared video footage of DM
      stripping with BSS, with continuous air and with manual injection of air into the
      AC to determine DM stripping duration and the number of times the surgeon had to
      insert and retrieve a surgical instrument from the AC. RESULTS: Thirty videos of
      10 consecutive cases of the three DM stripping techniques were evaluated. DM
      stripping duration was 3.26 (+/-1.32), 3.92 (+/-1.2) and 12.9 (+/-3.98) minutes
      for BSS, continuous air flow, and manual air injection, respectively. Frequency
      of instrument retrieval (FIR) was 3.6 (+/-1.71), 1.5 (+/-0.71) and 15.1 (+/-3.28)
      for BSS, continuous air flow, and manual air injection, respectively. Continuous
      air flow and BSS were both statistically different than manual air injection into
      the AC (p < 0.05), but did not differ from one another statistically. CONCLUSION:
      DM stripping during posterior lamellar surgery is imperative for favorable post
      operative results and prevention of complications. Performing this step under air
      in the AC contributes to better visualization and an efficient surgery.

PMID- 28456827
TI  - Three-Dimensional Modeling in Congenital and Structural Heart Perioperative Care
      and Education: A Path in Evolution.

PMID- 28456828
TI  - Resource Utilization Associated with Extracardiac Co-morbid Conditions Following
      Congenital Heart Surgery in Infancy.
AB  - Congenital heart disease (CHD) is often associated with chronic extracardiac co
      morbid conditions (ECC). The presence of ECC has been associated with greater
      resource utilization during the operative period; however, the impact beyond
      hospital discharge has not been described. This study sought to understand the
      scope of chronic ECC in infants with CHD as well as to describe the impact of ECC
      on resource utilization after discharge from the index cardiac procedure. IRB
      approved this retrospective study of infants <1 year who had cardiac surgery from
      2006 and 2011. Demographics, diagnoses, procedures, STAT score, and ECC were
      extracted from the medical record. Administrative data provided frequency of
      clinic and emergency room visits, admissions, cumulative hospital days, and
      hospital charges for 2 years after discharge from the index procedure. Data were
      compared using Mann-Whitney Rank Sum Test with p < 0.05 considered significant.
      ECC occurred in 55% (481/876) of infants. Median STAT score was higher in the
      group with ECC (3 vs. 2, p < 0.001). Resource utilization after discharge from
      the index procedure as defined by median hospital charges (78 vs. 10 K, p < 0.001
      and unplanned hospital days 4 vs. 0, p < 0.001) was higher in those with ECC, and
      increased with the greater number of ECC, even after accounting for surgical
      complexity. STAT score and the presence of multiple ECC were associated with
      higher resource utilization following the index cardiac surgical procedure. These
      data may be helpful in deciding which children might benefit from a cardiac
      complex care program that partners families and providers to improve health and
      decrease healthcare costs.

PMID- 28456829
TI  - The Evolution of a Pediatric Ventricular Assist Device Program: The Boston
      Children's Hospital Experience.
AB  - Mechanical circulatory support in the form of ventricular assist devices (VADs)
      in children has undergone rapid growth in the last decade. With expansion of
      device options available for larger children and adolescents, the field of
      outpatient VAD support has flourished, with many programs unprepared for the
      clinical, programmatic, and administrative responsibilities. From preimplantation
      VAD evaluation and patient education to postimplant VAD management, the VAD
      program, staffed with an interdisciplinary team, is essential to providing safe,
      effective, and sustainable care for a new technology in an exceedingly complex
      patient population. Herein, this paper describes the Boston Children's Hospital
      VAD experience over a decade and important lessons learned from developing a
      pediatric program focusing on a high-risk but low-volume population. We highlight
      the paramount role of the VAD coordinator, clinical infrastructure requirements,
      as well as innovation in care spanning inpatient and outpatient VAD supports at
      Boston Children's Hospital.

PMID- 28456830
TI  - Erratum to: Decreased Diastolic Ventricular Kinetic Energy in Young Patients with
      Fontan Circulation Demonstrated by Four-Dimensional Cardiac Magnetic Resonance
      Imaging.

PMID- 28456831
TI  - Clinical Application of the QRS-T Angle for the Prediction of Ventricular
      Arrhythmias in Patients with the Fontan Palliation.
AB  - Fontan palliation patients are at risk for ventricular arrhythmias post
      operatively. This study aimed to evaluate whether differences in the spatial QRS
      T angle can reliably predict ventricular arrhythmias in patients who had
      undergone Fontan palliation. A total of 117 patients who had the Fontan
      palliation and post-Fontan catheterization were included. Ventricular arrhythmias
      were identified in nine patients. Measurements of ECG parameters including QRS
      vector magnitude, QRS duration, corrected QT interval, and spatial peaks QRS-T
      angles were performed, and compared between those with and without ventricular
      arrhythmias. The only ECG parameter to distinguish those with versus those
      without VA was the SPQRS-T angle (p < 0.001), which at a cut-off value of 102.9
      degrees  gave sensitivity, specificity, positive and negative predictive values
      of 100.0, 57.0, 17.6 and 100.0%, respectively. Only the spatial peaks QRS-T angle
      differentiated those with and without ventricular arrhythmia development with a
      univariate HR 1.237 (95% CI 1.021-1.500) and a multivariate HR of 1.032 (1.009
      1.056) when catheter measured parameters were taken into account. In Fontan
      patients, the spatial peaks QRS-T angle is a significant independent predictor of
      ventricular arrhythmias. Clinical usefulness of this parameter remains to be seen
      and should be tested prospectively.

PMID- 28456832
TI  - Z-score of Mitral Annular Plane Systolic Excursion is a Useful Indicator of
      Evaluation of Left Ventricular Function in Patients with Acute-Phase Kawasaki
      Disease.
AB  - We previously reported the clinical usefulness of the mitral annular plane
      systolic excursion (MAPSE) to evaluate the left ventricular (LV) function in
      patients with Kawasaki disease (KD) in the acute-phase. However, the feasibility
      of the MAPSE z-score has not been evaluated in patients with acute KD. We
      prospectively studied 60 KD patients without coronary aneurysms. The MAPSE z
      scores were calculated using our standard MAPSE data. Brain natriuretic peptide
      (BNP) was measured as a parameter of LV function. In total, 281 healthy age- and
      body size-matched subjects were chosen as the control group. The MAPSE z-score
      decreased in the acute-phase (median value, -1.4) and increased in the
      convalescent phase (median value, 0.18; P < 0.0001). However, there was no
      significant difference in the MAPSE z-score between patients in the convalescent
      phase and the control patients (0.18 vs. 0.02, P = 0.199). Multivariate
      regression analysis revealed that BNP was an independent predictor of the MAPSE z
      score (beta = 0.40, P < 0.005). According to the receiver operating
      characteristic (ROC) analysis, the optimal cutoff value for the MAPSE z-score to
      judge LV dysfunction was -0.9. The MAPSE z-score is a useful index to evaluate LV
      function, and the cutoff value of -0.9 can be an indicator to judge LV
      dysfunction in the patients with acute-phase KD.

PMID- 28456833
TI  - Relationship Between Fragmented QRS Complexes and Cardiac Status in Duchenne
      Muscular Dystrophy: Multimodal Validation Using Echocardiography, Magnetic
      Resonance Imaging, and Holter Monitoring.
AB  - The presence of fragmented QRS is a known marker of heterogeneous ventricular
      activation around the myocardial scar area. We validated whether fragmented QRS
      shows any association with ventricular dysfunction, fibrosis, or ventricular
      arrhythmias in patients with Duchenne muscular dystrophy (DMD). Thirty-seven
      patients with DMD were evaluated using electrocardiography (ECG),
      echocardiography, cardiac magnetic resonance, and 24-h Holter monitoring.
      Associations between fragmented QRS and ventricular dysfunction, fibrosis, or
      ventricular arrhythmia were investigated. Fragmented QRS complexes were present
      in 31 of 37 (83.7%) patients, and they were associated with a significantly lower
      left ventricular ejection fraction along with an increased left ventricular Tei
      index as evaluated by echocardiography, and more frequent ventricular arrhythmia
      as indicated using 24-hour Holter monitoring compared with patients without
      fragmented QRS. The number of leads with fragmented QRS correlated negatively
      with left ventricular ejection fraction both using echocardiography (r = -0.616)
      and CMR (r = -0.516). Further, the number of leads with fragmented QRS showed a
      significant correlation with several other echocardiographic measurements (mitral
      Em and Sm, and left ventricular Tei index), and 2-dimensional speckle-tracking
      echocardiography derived global left ventricular longitudinal strain. The
      frequency of ventricular arrhythmia observed using Holter monitoring showed a
      significant positive correlation with the frequency of fragmented QRS on ECG (r =
      0.674). There was a positive trend of correlation between fragmented QRS and the
      amount of myocardial fibrosis as assessed by late gadolinium enhancement using
      CMR, but the statistical significance of the relationship was low (r = 0.433, p =
      0.056). Fragmentation of QRS complexes is associated with degrees of left
      ventricular dysfunction, fibrosis, and ventricular arrhythmias in patients with
      DMD.

PMID- 28456836
TI  - Commentary to: "Improving the thiobarbituric acid-reactive-substances assay for
      estimating lipid peroxidation in plant tissues containing anthocyanin and other
      interfering compounds" by Hodges et al., Planta (1999) 207:604-611.

PMID- 28456834
TI  - Spermatogenic failure and the Y chromosome.
AB  - The Y chromosome harbors a number of genes essential for testis development and
      function. Its highly repetitive structure predisposes this chromosome to
      deletion/duplication events and is responsible for Y-linked copy-number
      variations (CNVs) with clinical relevance. The AZF deletions remove genes with
      predicted spermatogenic function en block and are the most frequent known
      molecular causes of impaired spermatogenesis (5-10% of azoospermic and 2-5% of
      severe oligozoospermic men). Testing for this deletion has both diagnostic and
      prognostic value for testicular sperm retrieval in azoospermic men. The most
      dynamic region on the Yq is the AZFc region, presenting numerous NAHR hotspots
      leading to partial losses or gains of the AZFc genes. The gr/gr deletion (a
      partial AZFc deletion) negatively affects spermatogenic efficiency and it is a
      validated, population-dependent risk factor for oligozoospermia. In certain
      populations, the Y background may play a role in the phenotypic expression of
      partial AZFc rearrangements and similarly it may affect the predisposition to
      specific deletions/duplication events. Also, the Yp contains a gene array, TSPY1,
      with potential effect on germ cell proliferation. Despite intensive
      investigations during the last 20 years on the role of this sex chromosome in
      spermatogenesis, a number of clinical and basic questions remain to be answered.
      This review is aimed at providing an overview of the role of Y chromosome-linked
      genes, CNVs, and Y background in spermatogenesis.

PMID- 28456835
TI  - Past successes and future opportunities for the genetics of the human Y
      chromosome.

PMID- 28456837
TI  - 18F-FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive
      and HER2-positive breast cancer.
AB  - OBJECTIVES: This study assesses 18F-FDG-PET/CT for patients with newly diagnosed
      estrogen receptor-positive/human epidermal growth factor receptor-negative
      (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast
      cancer. METHODS: In this Institutional Review Board-approved retrospective study,
      our Healthcare Information System was screened for patients with ER+/HER2- and
      HER2+ breast cancer who underwent 18F-FDG-PET/CT prior to systemic or radiation
      therapy. The initial stage was determined from mammography, ultrasound, magnetic
      resonance imaging, and/or surgery.18F-FDG-PET/CT was evaluated to identify
      unsuspected extra-axillary regional nodal and distant metastases. The proportion
      of patients upstaged overall and stratified by stage and receptor phenotypes was
      calculated along with confidence intervals (CI). RESULTS: A total of 238 patients
      with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were
      evaluated. For patients with ER+/HER2-breast cancer, 18F-FDG-PET/CT revealed
      unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage
      IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, 18F-FDG
      PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA,
      13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for
      IIB was 14% (95% confidence interval (CI): 9-20%). CONCLUSIONS: 18F-FDG-PET/CT
      revealed distant metastases in 14% (95% CI: 9-20%) of patients with stage IIB
      ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously
      seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9
      24%). The detection of unsuspected distant metastases in these patients alters
      treatment and prognosis. NCCN guidelines should consider adding patients with
      stage IIB breast cancer for consideration of systemic staging with 18F-FDG-PET/CT
      at the time of initial diagnosis.

PMID- 28456838
TI  - Theoretical Study of Molecular Transport Through a Permeabilized Cell Membrane in
      a Microchannel.
AB  - A two-dimensional model is developed to study the molecular transport into an
      immersed cell in a microchannel and to investigate the effects of finite boundary
      (a cell is suspended in a microchannel), amplitude of electric pulse, and
      geometrical parameter (microchannel height and size of electrodes) on cell
      uptake. Embedded electrodes on the walls of the microchannel generate the
      required electric pulse to permeabilize the cell membrane, pass the ions through
      the membrane, and transport them into the cell. The shape of electric pulses is
      square with the time span of 6 ms; their intensities are in the range of 2.2,
      2.4, 2.6, 3 V. Numerical simulations have been performed to comprehensively
      investigate the molecular uptake into the cell. The obtained results of the
      current study demonstrate that calcium ions enter the cell from the anodic side
      (the side near positive electrode); after a while, the cell faces depletion of
      the calcium ions on a positive electrode-facing side within the microchannel; the
      duration of depletion depends on the amplitude of electric pulse and geometry
      that lasts from microseconds to milliseconds. By keeping geometrical parameters
      and time span constant, increment of a pulse intensity enhances molecular uptake
      and rate of propagation inside the cell. If a ratio of electrode size to cell
      diameter is larger than 1, the transported amount of Ca 2+ into the cell, as well
      as the rate of propagation, will be significantly increased. By increasing the
      height of the microchannel, the rate of uptake is decreased. In an infinite
      domain, the peak concentration becomes constant after reaching the maximum value;
      this value depends on the intra-extracellular conductivity and diffusion
      coefficient of interior and exterior domains of the cell. In comparison, the
      maximum concentration is changed by geometrical parameters in the microchannel.
      After reaching the maximum value, the peak concentration reduces due to the
      depletion of Ca 2+ ions within the microchannel. Electrophoretic velocity has a
      significant effect on the cell uptake.

PMID- 28456839
TI  - Hypothermia provokes hemorrhaging in various core muscle groups: how many of them
      could we have missed?
AB  - The postmortem diagnosis of hypothermia remains problematic even in the era of
      molecular and digital diagnostic advances. Gross hemorrhages in iliopsoas muscles
      have been regarded as a helpful diagnostic sign in hypothermia fatalities;
      nevertheless, they have received marginal attention since their original
      description. The present study attempts to fill that void by examining
      occurrence, localization, and diagnostic significance of the bleeding into the
      core muscles as evidence of death due to hypothermia in a series comprising 51
      consecutive hypothermia autopsy cases. Hemorrhages into the core muscles were
      identified in 33 cases of fatal hypothermia (65%). Hemorrhages were present in
      iliopsoas muscles (19 cases; 37%), deep back muscles (18 cases; 35%), and in
      other core muscular groups such as the diaphragm, cervical, pectoral, and
      intercostal muscles (11 cases; 22%). The results of the study offer an attractive
      diagnostic opportunity and reaffirm the potential of the careful core muscle
      dissection for the clarification of hypothermic deaths. Centers lacking high-end
      imaging technologies and molecular postmortem programs may especially benefit,
      which may have implications in broader autopsy practice.

PMID- 28456840
TI  - Rapid evidence review of the comparative effectiveness, harms, and cost
      effectiveness of pharmacogenomics-guided antidepressant treatment versus usual
      care for major depressive disorder.
AB  - OBJECTIVE: This study aims to conduct an evidence review of the effectiveness,
      harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment
      for major depressive disorder. METHODS: We searched MEDLINE(r), the Cochrane
      Central Registry of Controlled Trials, and PsycINFO through February 2017. We
      used prespecified criteria to select studies, abstract data, and rate internal
      validity and strength of the evidence (PROSPERO number CRD42016036358). RESULTS:
      We included two randomized trials (RCT), five controlled cohort studies, and six
      modeling studies of mostly women in their mid-40s with few comorbidities. CNSDose
      (ABCB1, ABCC1, CYP2C19, CYP2D6, UGT1A1) is the only pharmacogenomics test that
      significantly improved remission (one additional remitting patient in 12 weeks
      per three genotyped, 95% CI 1.7 to 3.5) and reduced intolerability in an RCT.
      ABCB1 genotyping leads to one additional remitting patient in 5 weeks per three
      genotyped (95% CI 3 to 20), but tolerability was not reported. In an RCT,
      GeneSight (CYP2D6, CYPC19, CYP1A2, SLC6A4, HTR2A) did not statistically
      significantly improve remission, and evidence is inconclusive about its
      tolerability. Evidence is generally low strength because RCTs were few and
      underpowered. Cost-effectiveness is unclear due to lack of directly observed cost
      effectiveness outcomes. We found no studies that evaluated whether
      pharmacogenomics shortens time to optimal treatment, whether improvements were
      due to switches to genetically congruent medication, or whether effectiveness
      varies based on test and patient characteristics. CONCLUSIONS: Certain
      pharmacogenomics tools show promise of improving short-term remission rates in
      women in their mid-40s with few comorbidities. But, important evidence
      limitations preclude recommending their widespread use and indicate a need for
      further research.

PMID- 28456842
TI  - IL18 receptors are required for IL-37-mediated epithelial ovarian tumor
      progression.

PMID- 28456841
TI  - Changes in gene expression and sensitivity of cocaine reward produced by a
      continuous fat diet.
AB  - RATIONALE: Preclinical studies report that free access to a high-fat diet (HFD)
      alters the response to psychostimulants. OBJECTIVES: The aim of the present study
      was to examine how HFD exposure during adolescence modifies cocaine effects. Gene
      expression of CB1 and mu-opioid receptors (MOr) in the nucleus accumbens (N Acc)
      and prefrontal cortex (PFC) and ghrelin receptor (GHSR) in the ventral tegmental
      area (VTA) were assessed. METHODS: Mice were allowed continuous access to fat
      from PND 29, and the locomotor (10 mg/kg) and reinforcing effects of cocaine (1
      and 6 mg/kg) on conditioned place preference (CPP) were evaluated on PND 69.
      Another group of mice was exposed to a standard diet until the day of post
      conditioning, on which free access to the HFD began. RESULTS: HFD induced an
      increase of MOr gene expression in the N Acc, but decreased CB1 receptor in the N
      Acc and PFC. After fat withdrawal, the reduction of CB1 receptor in the N Acc was
      maintained. Gene expression of GHSR in the VTA decreased during the HFD and
      increased after withdrawal. Following fat discontinuation, mice exhibited
      increased anxiety, augmented locomotor response to cocaine, and developed CPP for
      1 mg/kg cocaine. HFD reduced the number of sessions required to extinguish the
      preference and decreased sensitivity to drug priming-induced reinstatement.
      CONCLUSION: Our results suggest that consumption of a HFD during adolescence
      induces neurobiochemical changes that increased sensitivity to cocaine when fat
      is withdrawn, acting as an alternative reward.

PMID- 28456843
TI  - Dynamic nucleolar activity in wheat * Aegilops hybrids: evidence of C-genome
      dominance.
AB  - KEY MESSAGE: NOR loci of C-subgenome are dominant in wheat * Aegilops
      interspecific hybrids, which may have evolutionary implications for wheat group
      genome dynamics and evolution. After interspecific hybridisation, some genes are
      often expressed from only one of the progenitor species, shaping subsequent
      allopolyploid genome evolution processes. A well-known example is nucleolar
      dominance, i.e. the formation of cell nucleoli from chromosomes of only one
      parental species. We studied nucleolar organizing regions (NORs) in diploid
      Aegilops markgrafii (syn: Ae. caudata; CC), Ae. umbellulata (UU), allotetraploids
      Aegilops cylindrica (CcCcDcDc) and Ae. triuncialis (CtCtUtUt), synthetic
      interspecific F1 hybrids between these two allotetraploids and bread wheat
      (Triticum aestivum, AABBDD) and in F3 generation hybrids with genome composition
      AABBDDCtCtUtUt using silver staining and fluorescence in situ hybridization
      (FISH). In Ae. markgrafii (CC), NORs of both 1C and 5C or only 5C chromosome
      pairs were active in different individual cells, while only NORs on 1U
      chromosomes were active in Ae. umbellulata (UU). Although all 35S rDNA loci of
      the Ct subgenome (located on 1Ct and 5Ct) were active in Ae. triuncialis, only
      one pair (occupying either 1Cc or 5Cc) was active in Ae. cylindrica, depending on
      the genotype studied. These C-genome expression patterns were transmitted to the
      F1 and F3 generations. Wheat chromosome NOR activity was variable in Ae.
      triuncialis * T. aestivum F1 seeds, but silenced by the F3 generation. No effect
      of maternal or paternal cross direction was observed. These results indicate that
      C-subgenome NOR loci are dominant in wheat * Aegilops interspecific hybrids,
      which may have evolutionary implications for wheat group genome dynamics and
      allopolyploid evolution.

PMID- 28456844
TI  - Preclinical evaluation of the urokinase receptor-derived peptide UPARANT as an
      anti-inflammatory drug.
AB  - BACKGROUND: Inflammation plays a key role in the pathogenesis of several chronic
      diseases. The urokinase plasminogen activator receptor (uPAR) exerts a plethora
      of functions in both physiological and pathological processes, including
      inflammation. OBJECTIVE AND DESIGN: In this study, we evaluated the anti
      inflammatory effect of a novel peptide ligand of uPAR, UPARANT, in different
      animal models of inflammation. SUBJECTS AND TREATMENT: Rats and mice were divided
      in different groups (n = 5) for single or repeated administration of vehicle (9%
      DMSO in 0.9% NaCl), UPARANT (6, 12 and 24 mg/kg) or dexamethasone (2 mg/kg).
      Animals were subjected to carrageenan-induced paw oedema or zymosan-induced
      peritonitis. METHODS: UPARANT effects were tested on: (1) the carrageenan-induced
      paw oedema volume, (2) the expression of inducible nitric oxide synthase (iNOS)
      and cyclooxygenase-2 (COX-2) and the nitrite/nitrate (NOx) levels in the paw
      exudates, (3) cells recruitment into the peritoneal cavity after zymosan
      injection and (4) NOx levels in the peritoneal lavage. RESULTS: UPARANT (12 and
      24 mg/kg) reduced inflammation in both experimental paradigms. Analysis of pro
      inflammatory enzymes revealed that administration of UPARANT reduced iNOS, COX2
      and NO over-production. CONCLUSIONS: Our study provides a solid evidence that
      UPARANT reduces the severity of inflammation in diverse animal models, thus
      representing a novel anti-inflammatory drug with potential advantages with
      respect to the typical steroidal agents.

PMID- 28456845
TI  - In focus in HCB.

PMID- 28456846
TI  - Comparison of urinary iodine levels in women of childbearing age during and after
      pregnancy.
AB  - PURPOSE: Median urinary iodine concentration (UIC) is used to describe the iodine
      status of a population. However, the link between UIC and iodine intake may vary
      during pregnancy. The aim of this study was to compare UIC during and after
      pregnancy, adjusting for factors that affect iodine intake. METHODS: Two repeated
      measures of UIC and data on maternal iodine intake estimated through
      questionnaires were collected during pregnancy and 1-4 years after pregnancy in a
      subsample of women (n = 598) from a mother and child cohort study in Spain.
      Random-effects interval regression was used to assess the changes in UIC
      according to pregnancy status. RESULTS: Median UIC was similar during (133 MUg/L)
      and after pregnancy (139 MUg/L). After adjusting for iodised salt, iodine
      supplement consumption, and socio-demographic related variables, UIC was 24.0%
      (95% CI 11.3, 38.2) higher after than during pregnancy. This difference was
      maintained in a subsample of women with exhaustive information on diet (n = 291):
      26.2%, 95% CI 10.3, 44.4. CONCLUSIONS: In an iodine sufficient area for the
      general population, iodine excretion was lower during than after pregnancy when
      factors affecting iodine intake were controlled for. Current recommendations of
      median UIC during pregnancy are based on the equivalence between iodine intake
      and UIC estimated from studies in non-pregnant populations, which might lead to
      overestimation of iodine deficiency during gestation. Further studies should
      evaluate the equivalence between iodine intake and its urinary excretion during
      pregnancy.

PMID- 28456847
TI  - Efficacy of chitosan dressing on endoscopic sinus surgery: a systematic review
      and meta-analysis.
AB  - Chitosan dressing might be promising to promote the recovery following endoscopic
      sinus surgery (ESS). However, the results remain controversial. We conducted a
      systematic review and meta-analysis to explore the influence of chitosan dressing
      on ESS. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases
      were systematically searched. Randomized controlled trials (RCTs) assessing the
      effect of chitosan dressing on endoscopic sinus surgery were included. Two
      investigators independently searched articles, extracted data, and assessed the
      quality of included studies. The primary outcomes were synechia and hemostasis.
      Meta-analysis was performed using random-effect model. Four RCTs involving 268
      patients were included in the meta-analysis. Overall following ESS, compared with
      control intervention, chitosan dressing significantly reduced synechia (RR =
      0.25; 95% CI 0.13-0.49; P < 0.0001) and promoted hemostasis (RR = 1.70; 95% CI
      1.37-2.11; P < 0.00001), but showed no impact on granulations (RR = 1.18; 95% CI
      0.72-1.95; P = 0.52), mucosal edema (RR = 0.88; 95% CI 0.60-1.29; P = 0.51),
      crusting (RR = 0.85; 95% CI 0.48-1.53; P = 0.60), and infection (RR = 0.88; 95%
      CI 0.51-1.52; P = 0.64). Compared to control intervention, chitosan dressing
      could significantly decrease edema and improve hemostasis, but had no effect on
      granulations, mucosal edema, crusting and infection.

PMID- 28456848
TI  - Range of S-100beta levels during functional endoscopic sinus surgery with
      moderately controlled hypotension.
AB  - The aim of this study is to determine the range of S-100beta levels during
      functional endoscopic sinus surgery (FESS) when the mean arterial pressure (MAP)
      was controlled within 60-70 mmHg. After anesthesia induction with propofol and
      remifentanil, the patient was positioned in the reverse Trendelenburg position
      and MAP was controlled within 60-70 mmHg during surgery. For the S-100beta assay,
      blood was taken from a radial arterial catheter before (baseline) and at 20 (T
      20) and 60 (T 60) min after setting the reverse Trendelenburg position and
      controlled hypotension, and at 60 (T post60) min after the end of the operation.
      In total, 34 patients completed the study. Baseline S-100beta was 0.00837 +/-
      0.00785 ng/mL. The levels at T 20 and T 60 were 0.02057 +/- 0.01739 and 0.01987
      +/- 0.01145 ng/mL, respectively. The level of T post60 was 0.05436 +/- 0.02318
      ng/mL. The level at T 20 increased significantly versus the baseline level (P <
      0.001); there were no significant differences between T 20 and T 60. The level at
      T post60 was significantly different versus T 20 and T 60 (P < 0.001). However,
      all S-100beta levels were within the normal range. S-100beta-a sensitive
      biomarker of cerebral ischemia-was within the normal range during FESS when
      moderate hypotension (MAP >60 mmHg) was provided. Thus, moderate hypotension
      would be seemed to be a safe and effective anesthetic technique for FESS without
      risk for cerebral ischemia.

PMID- 28456849
TI  - Can common serum biomarkers predict complicated appendicitis in children?
AB  - PURPOSE: As appendicitis in children can be managed differently according to the
      severity of the disease, we investigated whether commonly used serum biomarkers
      on admission could distinguish between simple and complicated appendicitis.
      METHODS: Admission white blood cell (WBC), neutrophil (NEU), and C-reactive
      protein (CRP) levels were analysed by ROC curve, and Kruskal-Wallis and
      contingency tests. Patients were divided according to age and histology [normal
      appendix (NA), simple appendicitis (SA), complicated appendicitis (CA)]. RESULTS:
      Of 1197 children (NA = 186, SA = 685, CA = 326), 7% were <5 years, 55% 5-12, 38%
      13-17. CA patients had higher CRP and WBC levels than NA and SA (p < 0.0001). NEU
      levels were lower in NA compared to SA or CA (p < 0.0001), but were similar
      between SA and CA (p = 0.6). CA patients had higher CRP and WBC levels than SA
      patients in 5-12- (p < 0.0001) and 13-17-year groups (p = 0.0075, p = 0.005), but
      not in <5-year group (p = 0.72, p = 0.81). We found CRP >40 mg/L in 58% CA and
      37% SA (p < 0.0001), and WBC >15 * 109/L in 58% CA and 43% SA (p < 0.0001).
      CONCLUSIONS: Admission CRP and WBC levels may help the clinician predict
      complicated appendicitis in children older than 5 years of age. Early distinction
      of appendicitis severity using these tests may guide caregivers in the
      preoperative decision-making process.

PMID- 28456850
TI  - Influence of body mass index on survival in indolent and mantle cell lymphomas:
      analysis of the StiL NHL1 trial.
AB  - Obesity is a well-known risk factor for the development of cancer, but its
      influence on the course of disease is still controversial. We investigated the
      influence of body mass index (BMI) on overall survival (OS) in 502 patients with
      indolent non-Hodgkin's lymphoma or mantle cell lymphoma in a subgroup analysis of
      the StiL (Study Group Indolent Lymphomas) NHL1 trial. We defined a cut-off of
      22.55 kg/m2 by ROC calculation and Youden Index analysis and stratified patients
      into "low BMI" and "high BMI". Five-year OS was significantly longer in the high
      BMI group (82.2%) when compared to that of the low BMI group (66.2%) (HR 0.597;
      95%CI 0.370-0.963; p = 0.034). BMI was also an independent prognostic factor for
      OS in multivariate analysis (HR 0.541; 95%CI 0.332-0.883; p = 0.014). Of note,
      patients had a significantly lower BMI in the presence than patients in the
      absence of B-symptoms (p = 0.025). BMI significantly impacts on OS in indolent
      non-Hodgkin's lymphoma and mantle cell lymphoma, which may be influenced by the
      effect of B-symptoms on BMI.

PMID- 28456851
TI  - Ruxolitinib reduces JAK2 p.V617F allele burden in patients with polycythemia vera
      enrolled in the RESPONSE study.
AB  - In patients with polycythemia vera (PV), an elevated JAK2 p.V617F allele burden
      is associated with indicators of more severe disease (e.g., leukocytosis,
      splenomegaly, and increased thrombosis risk); however, correlations between
      allele burden reductions and clinical benefit in patients with PV have not been
      extensively evaluated in a randomized trial. This exploratory analysis from the
      multicenter, open-label, phase 3 Randomized Study of Efficacy and Safety in
      Polycythemia Vera With JAK Inhibitor INCB018424 Versus Best Supportive Care trial
      evaluated the long-term effect of ruxolitinib treatment on JAK2 p.V617F allele
      burden in patients with PV. Evaluable JAK2 p.V617F-positive patients randomized
      to ruxolitinib (n = 107) or best available therapy (BAT) who crossed over to
      ruxolitinib at week 32 (n = 97) had consistent JAK2 p.V617F allele burden
      reductions throughout the study. At all time points measured (up to weeks 208
      [ruxolitinib-randomized] and 176 [ruxolitinib crossover]), mean changes from
      baseline over time in JAK2 p.V617F allele burden ranged from -12.2 to -40.0%
      (ruxolitinib-randomized) and -6.3 to -17.8% (ruxolitinib crossover). Complete or
      partial molecular response was observed in 3 patients (ruxolitinib-randomized, n
      = 2; ruxolitinib crossover, n = 1) and 54 patients (ruxolitinib-randomized, n =
      33; ruxolitinib crossover, n = 20; BAT, n = 1), respectively. Among patients
      treated with interferon as BAT (n = 13), the mean maximal reduction in allele
      burden from baseline was 25.6% after crossover to ruxolitinib versus 6.6% before
      crossover. Collectively, the data from this exploratory analysis suggest that
      ruxolitinib treatment for up to 4 years provides progressive reductions in JAK2
      p.V617F allele burden in patients with PV who are resistant to or intolerant of
      hydroxyurea. The relationship between allele burden changes and clinical outcomes
      in patients with PV remains unclear.

PMID- 28456853
TI  - Cultured Meat in Islamic Perspective.
AB  - Cultured meat is a promising product that is derived through biotechnology that
      partially circumvents animal physiology, thereby being potentially more
      sustainable, environmentally friendly and animal friendly than traditional
      livestock meat. Such a novel technology that can impact many consumers evokes
      ethical, philosophical and religious discussions. For the Islamic community, the
      crucial question is whether cultured meat is halal, meaning compliant with
      Islamic laws. Since the culturing of meat is a new discovery, invention and
      innovation by scientists that has never been discussed by classical jurists
      (fuqaha'), an ijtihad by contemporary jurists must look for and provide answers
      for every technology introduced, whether it comply the requirements of Islamic
      law or not. So, this article will discuss an Islamic perspective on cultured meat
      based on the original scripture in the Qur'an and interpretations by
      authoritative Islamic jurists. The halal status of cultured meat can be resolve
      through identifying the source cell and culture medium used in culturing the
      meat. The halal cultured meat can be obtained if the stem cell is extracted from
      a (Halal) slaughtered animal, and no blood or serum is used in the process. The
      impact of this innovation will give positive results in the environmental and
      sustain the livestock industry.

PMID- 28456852
TI  - Fluid-induced lung injury-role of TRPV4 channels.
AB  - Administration of bolus intravenous fluid is associated with respiratory
      dysfunction and increased mortality, findings with no clear mechanistic
      explanation. The objective of this study was to examine whether bolus intravenous
      (i.v.) fluid administration results in acute lung injury in a rat model and
      further, to examine whether this injury is associated with transient receptor
      potential vallinoid (TRPV)4 channel function and endothelial inflammatory
      response. Healthy male Sprague-Dawley rats were administered 60 ml/kg 0.9% saline
      i.v. over 30 min. Manifestation of acute lung injury was assessed by lung
      physiology, morphology, and markers of inflammation. The role of TRPV4 channels
      in fluid-induced lung injury was subsequently examined by the administration of
      ruthenium red (RR) in this established rat model and again in TRPV4 KO mice. In
      endothelial cell culture, permeability and P-selectin expression were measured
      following TRPV4 agonist with and without antagonist; 0.9% saline resulted in an
      increase in lung water, lavage protein and phospholipase A2, and plasma
      angiopoietin-2, with worsening in arterial blood oxygen (PaO2), lung elastance,
      surfactant activity, and lung histological injury score. These effects were
      ameliorated following i.v. fluid in rats receiving RR. TRPV4 KO mice did not
      develop lung edema. Expression of P-selectin increased in endothelial cells
      following administration of a TRPV4 agonist, which was ameliorated by
      simultaneous addition of RR. Bolus i.v. 0.9% saline resulted in permeability
      pulmonary edema. Data from ruthenium red, TRPV4 KO mice, and endothelial cell
      culture suggest activation of TRPV4 and release of angiopoietin 2 and P-selectin
      as the central mechanism.

PMID- 28456854
TI  - Anterior support reduces the stresses on the posterior instrumentation after
      pedicle subtraction osteotomy: a finite-element study.
AB  - STUDY DESIGN: The investigation was based on finite-element simulations.
      OBJECTIVE: Pedicle subtraction osteotomy (PSO) is an effective but technical
      demanding surgical technique, associated with a high risk of rod failure. The
      present study aims at investigating the role of the anterior support in
      combination with PSO, with a numerical comparative analysis. METHODS: An
      osteotomy was simulated at the L3 level of a lumbosacral spine. An implantation
      of various combinations of devices for the anterior (1 or 2 cages of different
      material) and posterior stabilization (1 or 2 rods) was then performed. ROM,
      loads, and stresses acting on the rods were calculated. RESULTS: A 4-8% reduction
      of the ROM was obtained introducing one or two cages in the instrumented model.
      However, the anterior support had only a minor influence on the ROM. The load on
      the posterior instrumentation decreased up to 8% using one cage and about 15%
      with two anterior devices. A 20-30% reduction of the stresses on the rods was
      calculated inserting one cage and up to 50% using two cages. Following the
      introduction of the anterior support, the greatest stress reduction was observed
      in the model having two cages and spinal fixators with two rods. CONCLUSIONS: The
      use of cages is crucial to ensure anterior support and decrease loads and
      stresses on the posterior instrumentation.

PMID- 28456855
TI  - Beyond vulnerability: how the dual role of patient-health care provider can
      inform health professions education.
AB  - In order to prepare fully competent health care professionals, health professions
      education must be concerned with the relational space between patients and
      providers. Compassion and compassionate care are fundamental elements of this
      relational space. Traditionally, health professions educators and leaders have
      gone to two narrative sources when attempting to better under constructs of
      compassion: patients or providers. Rarely have there been explorations of the
      perspectives of those who consider themselves as both patients and providers. In
      this study, we interviewed nineteen health care providers who self-disclosed as
      having had a substantive patient experience in the health care system. We engaged
      with these participants to better understand their experience of having these
      dual roles. Anchored in Foucault's concepts of subjectivity and Goffman's
      symbolic interactionism, the interviews in this study reveal practices of moving
      between the two roles of patient and provider. Through this exploration, we
      consider how it is that providers who have been patients understand themselves to
      be more compassionate whilst in their provider roles. Rather than describing
      compassion as a learnable behaviour or an innate virtue, we theoretically engage
      with one proposed mechanism of how compassion is produced. In particular, we
      highlight the role of critical reflexivity as an underexplored construct in the
      enactment of compassion. We discuss these findings in light of their implications
      for health professions education.

PMID- 28456856
TI  - Exploring trainer and trainee emotional talk in narratives about workplace-based
      feedback processes.
AB  - Emotion characterises learners' feedback experiences. While the failure-to-fail
      literature suggests that emotion may be important, little is known about the role
      of emotion for educators. Secondary analyses were therefore conducted on data
      exploring 110 trainers' and trainees' feedback experiences. Group and individual
      narrative interviews were conducted across three UK sites. We analysed 333
      narratives for emotional talk using textual analysis: Linguistic Inquiry and Word
      Count. Furthermore, thematic framework analysis was conducted on the trainer
      narratives to explore aspects of feedback processes that are emotional. An
      additional in-depth little 'd' discourse analysis was conducted on selected
      trainer narratives to enable us to explore the complex relationship between the
      whats (reported events) and the hows (emotional talk). Trainer narratives did not
      differ significantly in positive or negative emotional talk from trainee
      narratives. By exploring the interplay of the whats and the hows, several aspects
      of feedback processes were identified as potentially emotional for trainers
      including trainers being concerned about upsetting learners and worried about
      patient safety. This was illustrated through numerous linguistic devices to
      establish emotional tone such as metaphoric talk and laughter. These findings
      suggest that feedback processes can be emotional for trainers. It highlights the
      need to better understand the 'filter' of emotion for trainers but also to better
      understand how emotion plays a role in feedback as a complex social process.

PMID- 28456857
TI  - Age effect on prevalence of ultra-high risk for psychosis symptoms: replication
      in a clinical sample of an early detection of psychosis service.
AB  - Higher frequencies of perceptual and lesser clinical significance of non
      perceptual attenuated psychotic symptoms (APS) have been reported by 8- to 15
      year-old of the general population compared to 16- to 40-year-old. We examined if
      such an age-effect can also be detected in a clinical never-psychotic sample (N =
      133) referred to a specialized service for clinical suspicion of developing
      psychosis. APS and brief intermittent psychotic symptoms (BIPS) were assessed
      using items P1-P3 and P5 (non-perceptual), and P4 (perceptual) of the Structured
      Interview for Psychosis-Risk Syndromes, current axis-I disorders with the Mini
      International Neuropsychiatric Interview, and psychosocial functioning with the
      Social and Occupational Functioning Assessment Scale. In the sample, 64% reported
      APS (61%) or BIPS (7%); any perceptual APS/BIPS was reported by 43% and any non
      perceptual APS/BIPS by 44%. In correspondence to the results in the general
      population sample, perceptual but not non-perceptual APS/BIPS were significantly
      more frequent in younger age groups below the age of 16 (8-12 years: odds ratio
      (OR) = 4.7 (1.1-19.5); 13-15 years: OR = 2.7 (0.9-7.7); 20-24-year-old as
      reference group). An age-effect of APS/BIPS on the presence of any current axis-I
      disorder (59%) or functional difficulties (67%) was not detected. However, when
      onset requirements of APS criteria (onset/worsening in past year) were met, the
      likelihood of a psychiatric diagnosis increased significantly with advancing age.
      Overall, the replicated age-effect on perceptual APS/BIPS in this clinical sample
      highlights the need to examine ways to distinguish clinically relevant perceptual
      APS/BIPS from perceptual aberrations likely remitting over the course of
      adolescence.

PMID- 28456858
TI  - Higher Impulsivity and HIV-Risk Taking Behaviour in Males with Alcohol Dependence
      Compared to Bipolar Mania: A Pilot Study.
AB  - To study the association of impulsivity, high-risk behaviours and incidence of
      HIV infection in patients with alcohol dependence and bipolar mania. This was a
      cross-sectional hospital-based pilot study and the sample consisted of male
      patients divided into three groups: 25 patients with alcohol dependence and 25
      with bipolar mania as per ICD-10 Diagnostic Criteria for Research and 25 normal
      controls. Severity of Alcohol Dependence Questionnaire (SADQ) and Young Mania
      Rating Scale (YMRS) were administered on alcohol dependent and bipolar patients,
      respectively. All three groups were rated on Barrett's Impulsivity Scale (BIS)
      and HIV Risk-taking Behaviour Scale (HRBS). None of the patients tested positive
      for either HIV 1 or 2. BIS motor impulsivity, BIS total score and HRBS total
      score were significantly higher in alcohol dependent patients as compared to
      bipolar mania patients. In the Alcohol dependent group, BIS score significantly
      correlated with education years, age of onset of alcohol use and SADQ, whereas,
      HRBS total score significantly correlated with SADQ scores. In the bipolar mania
      group, BIS significantly correlated with YMRS, and total number of episodes,
      whereas, there was no significant correlation of HRBS total score with any
      clinical variable. The findings of this pilot study underscore the link between
      alcohol use disorder and the impulsive behaviours that can lead to HIV infection,
      and highlight that those risks are higher for individuals with alcohol dependency
      than for individuals with bipolar disorder.

PMID- 28456859
TI  - A Comparison of Visual Recognition of the Laryngopharyngeal Structures Between
      High and Standard Frame Rate Videos of the Fiberoptic Endoscopic Evaluation of
      Swallowing.
AB  - The purpose of this study was to assess whether or not high frame rate (HFR)
      videos recorded using high-speed digital imaging (HSDI) improve the visual
      recognition of the motions of the laryngopharyngeal structures during pharyngeal
      swallow in fiberoptic endoscopic evaluation of swallowing (FEES). Five healthy
      subjects were asked to swallow 0.5 ml water under fiberoptic nasolaryngoscopy.
      The endoscope was connected to a high-speed camera, which recorded the
      laryngopharyngeal view throughout the swallowing process at 4000 frames/s (fps).
      Each HFR video was then copied and downsampled into a standard frame rate (SFR)
      video version (30 fps). Fifteen otorhinolaryngologists observed all of the
      HFR/SFR videos in random order and rated the four-point ordinal scale reflecting
      the degree of visual recognition of the rapid laryngopharyngeal structure motions
      just before the 'white-out' phenomenon. Significantly higher scores, reflecting
      better visibility, were seen for the HFR videos compared with the SFR videos for
      the following laryngopharyngeal structures: the posterior pharyngeal wall (p =
      0.001), left pharyngeal wall (p = 0.015), right lateral pharyngeal wall (p =
      0.035), tongue base (p = 0.005), and epiglottis tilting (p = 0.005). However,
      when visualized with HFR and SFR, 'certainly clear observation' of the laryngeal
      structures was achieved in <50% of cases, because all the motions were not
      necessarily captured in each video. These results demonstrate the use of HSDI in
      FEES makes the motion perception of the laryngopharyngeal structures during
      pharyngeal swallow easier in comparison to SFR videos with equivalent image
      quality due to the ability of HSDI to depict the laryngopharyngeal motions in a
      continuous manner.

PMID- 28456860
TI  - Downbeat nystagmus as an initial clinical sign in spinocerebellar ataxia type 6.

PMID- 28456861
TI  - Early Impacts of Marijuana Legalization: An Evaluation of Prices in Colorado and
      Washington.
AB  - Following the legalization and regulation of marijuana for recreational purposes
      in states with medical markets, policymakers and researchers seek empirical
      evidence on how, and how fast, supply and demand changed over time. Prices are an
      indication of how suppliers and consumers respond to policy changes, so this
      study uses a difference-in-difference approach to exploit the timing of policy
      implementation and identify the impacts on marijuana prices 4-5 months after
      markets opened. This study uses unique longitudinal survey data of prices paid by
      consumers and a web-scraped dataset of dispensary prices advertised online for
      three U.S. medical marijuana states that all eventually legalized recreational
      marijuana. Results indicate there were no impacts on the prices paid for medical
      or recreational marijuana by state-representative residents within the short 4-
      to 5-months window following legalization. However, there were differences in how
      much people paid if they obtained marijuana for recreational purposes from a
      recreational store. Further analysis of advertised prices confirms this result,
      but further demonstrates heterogeneous responses in prices across types of
      commonly advertised strains; prices either did not change or increased depending
      on the strain type. A key implication of our findings is that there are both
      supply and demand responses at work in the opening of legalized markets,
      suggesting that evaluations of immediate effects may not accurately reflect the
      long run impact of legalization on consumption.

PMID- 28456862
TI  - Explaining peroneal neuropathy after ankle sprain.

PMID- 28456863
TI  - Performance and kinetics of ANAMMOX granular sludge with pH shock in a sequencing
      batch reactor.
AB  - As an efficient and cost-effective nitrogen removal process, anaerobic ammonium
      oxidation (ANAMMOX) could be well operated at suitable pH condition. However, pH
      shock occurred in different kinds of wastewater and affected ANANNOX process
      greatly. The present research aimed at studying the performance and kinetics of
      ANAMMOX granular sludge with pH shock. When influent pH was below 7.5, effluent
      [Formula: see text]-N and [Formula: see text]-N increased with decreasing pH. At
      Ph 6.0, effluent [Formula: see text]-N approached 100 mg/L, and the ratios of
      [Formula: see text] approached 2.2 and 1.3, respectively. Both greatly deviated
      from theoretical values. When influent pH was above 7.5, effluent [Formula: see
      text]-N and [Formula: see text]-N increased with increasing pH. At pH 9.0,
      ammonium removal rate (ARR) and nitrite removal rate (NRR) decreased to 0.011 +/-
      0.004 and 0.035 +/- 0.004 kg/(m3.d), respectively. Besides, [Formula: see text]
      N:[Formula: see text]-N deviated from theoretical value. Longer recovery time
      from pH 9.0 than from pH 6.0 indicated that alkaline surroundings inhibited
      anaerobic ammonium oxidizing bacteria (AAOB) greater. The sludge settling
      velocity was 2.15 cm/s at pH 7.5. However, it decreased to 2.02 cm/s when pH was
      9.0. Acidic pH had little effect on sludge size, but disintegration of ANAMMOX
      granule was achieved with pH of 9.0. The Bell-shaped (A) model and the Ratkowsky
      model were more applicable to simulate the effect resulting from pH shock on
      ANAMMOX activity (R2 > 0.95), and both could describe ANAMMOX activity well with
      pH shock. They indicated that qmax was 0.37 kg [Formula: see text]-N/(kgMLSS.d)
      at the optimum pH value (7.47) in present study. The minimum pH during which
      ANAMMOX occurred was 5.68 while the maximum pH for ANAMMOX reaction was 9.26.
      Based on nitrogen removal performance with different pH, strongly acidic (pH <=
      6.5) or alkaline (pH >= 8.5) inhibited ANAMMOX process. Besides, ANAMMOX appeared
      to be more susceptible to alkaline wastewater. Compared to extremely acidic
      condition (low pH), extremely alkaline condition (high pH) affected ANAMMOX
      granules much more.

PMID- 28456864
TI  - A randomized, controlled clinical trial to evaluate the immunogenicity of a
      PreS/S hepatitis B vaccine Sci-B-VacTM, as compared to Engerix B(r), among
      vaccine naive and vaccine non-responder dialysis patients.
AB  - BACKGROUND: Dialysis patients have a suboptimal response to hepatitis B (HBV)
      vaccination. This study aimed to compare the immunogenicity of two vaccines: the
      third-generation Sci-B-VacTM vs. the second-generation Engerix B(r). The cohort
      included two groups of dialysis patients: naive and previously vaccinated non
      responders. Primary endpoints were antibody titers >=10 IU/L at 3 and 7 month
      post-vaccination. Secondary objectives were seroprotection rates in vaccine-naive
      patients and in previously vaccinated non-responders. METHODS: Eighty-six
      patients were assigned to vaccine (Sci-B-VacTM or Engerix B(r)) using computer
      generated randomization, stratified by age, gender, diabetes, and previous HBV
      vaccination. Sci-B-VacTM was administered in three doses, 10 MUg, at 0, 1, and 6
      months in naive patients; or 20 MUg in previously vaccinated non-responders.
      Engerix B(r) included four doses, 40 MUg at 0, 1, 2, and 6 months. RESULTS: Each
      group had 43 patients. Seroconversion was 69.8% with Engerix B(r) vs. 73.2% with
      Sci-B-VacTM. Antibody titers at 7 months were higher with Sci-B-VacTM (266.4 +/-
      383.9, median 53.4) than with Engerix(r) (193.2 +/- 328.9, median 19). However,
      these differences were not significant, perhaps due to a suboptimal sample size.
      CONCLUSIONS: This study suggests comparable immunogenicity for both vaccines.
      Thus, we cannot reject the null hypothesis that there is no difference in
      seroconversion by vaccine type. It is noteworthy that naive patients were
      vaccinated with a standard dose of Sci-B-VacTM, while Engerix B(r) was
      administered at a double dose. Similarly, although mean antibody titer levels in
      the Sci-B-VacTM group were higher than in the Engerix(r) group, this difference
      did not reach significance. Consequently, a future clinical trial should recruit
      a larger cohort of patients, using a standard double-dose protocol in both
      groups.

PMID- 28456866
TI  - Basidiospores of Puccinia striiformis f. sp. tritici succeed to infect barberry,
      while Urediniospores are blocked by non-host resistance.
AB  - Stripe rust (Yellow rust) caused by Puccinia striiformis f. sp. tritici (Pst) is
      a major disease of wheat worldwide. The use of resistant cultivars to control Pst
      has been very effective, low-cost, and ecologically sound. However, virulence
      patterns of Pst can quickly change, which may render resistant cultivars
      susceptible. The discovery of infection of Berberis spp. by basidiospores of Pst
      in 2010 raised important concerns about the evolution of new virulent races of
      the pathogen. Little is known about the infection process of Berberis spp. by
      basidiospores of Pst and the interaction between Berberis spp. and asexual
      urediniospores. In this study, the interaction between Pst urediniospores and
      Berberis spp. was investigated at histological and cytological levels. Our
      results indicate that Berberis spp. expresses a continuum of layered defenses
      comprised of structural and chemical changes in the cell wall as well as post
      haustorial hypersensitive responses to urediniospore infection. Our study also re
      examines in detail the infection process of Pst basidiospores on Berberis spp.
      and provides useful information for further research on the molecular mechanisms
      governing the interaction between Berberis spp. and Pst.

PMID- 28456865
TI  - Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and
      glucose homeostasis in mice.
AB  - AIMS/HYPOTHESIS: Regulation of energy balance involves the participation of many
      factors, including nutrients, among which are circulating lipids, acting as
      peripheral signals informing the central nervous system of the energy status of
      the organism. It has been shown that neuronal lipoprotein lipase (LPL)
      participates in the control of energy balance by hydrolysing lipid particles
      enriched in triacylglycerols. Here, we tested the hypothesis that LPL in the
      mediobasal hypothalamus (MBH), a well-known nucleus implicated in the regulation
      of metabolic homeostasis, could also contribute to the regulation of body weight
      and glucose homeostasis. METHODS: We injected an adeno-associated virus (AAV)
      expressing Cre-green fluorescent protein into the MBH of Lpl-floxed mice (and
      wild-type mice) to specifically decrease LPL activity in the MBH. In parallel, we
      injected an AAV overexpressing Lpl into the MBH of wild-type mice. We then
      studied energy homeostasis and hypothalamic ceramide content. RESULTS: The
      partial deletion of Lpl in the MBH in mice led to an increase in body weight
      compared with controls (37.72 +/- 0.7 g vs 28.46 +/- 0.12, p < 0.001) associated
      with a decrease in locomotor activity. These mice developed hyperinsulinaemia and
      glucose intolerance. This phenotype also displayed reduced expression of Cers1 in
      the hypothalamus as well as decreased concentration of several C18 species of
      ceramides and a 3-fold decrease in total ceramide intensity. Conversely,
      overexpression of Lpl specifically in the MBH induced a decrease in body weight.
      CONCLUSIONS/INTERPRETATION: Our study shows that LPL in the MBH is an important
      regulator of body weight and glucose homeostasis.

PMID- 28456867
TI  - The Temporal Dynamics of Response Inhibition and their Modulation by Cognitive
      Control.
AB  - Behavioral adjustments require interactions between distinct modes of cognitive
      control and response inhibition. Hypothetically, fast and global inhibition is
      exerted in the reactive control mode, whereas proactive control enables the
      preparation of inhibitory pathways in advance while relying on the slower
      selective inhibitory system. We compared the temporal progression of inhibition
      in the reactive and proactive control modes using simultaneous
      electroencephalography (EEG) and electromyography (EMG) recordings. A selective
      stop signal task was used where go stimuli required bimanual responses, but only
      one hand's response had to be suppressed in stop trials. Reactive and proactive
      conditions were incorporated by non-informative and informative cues,
      respectively. In 47% of successful stop trials, subthreshold EMG activity was
      detected that was interrupted as early as 150 ms after stop stimulus
      presentation, indicating that inhibition occurs much earlier than previously
      thought. Inhibition latencies were similar across the reactive and proactive
      control modes. The EMG of the responding hand in successful selective stop trials
      indicated a global suppression of ongoing motor actions in the reactive
      condition, and less inhibitory interference on the ongoing actions in the
      proactive condition. Group-level second order blind separation (SOBI) was applied
      to the EEG to dissociate temporally overlapping event-related potentials. The
      components capturing the N1 and N2 were larger in the reactive than the proactive
      condition. P3 activity was distributed across four components, three of which
      were augmented in the proactive condition. Thus, although EEG indices were
      modulated by the control mode, the inhibition latency remained unaffected.

PMID- 28456868
TI  - Comparative Pathogenicity of Lomentospora prolificans (Scedosporium prolificans)
      Isolates from Mexican Patients.
AB  - We identified 11 Lomentospora prolificans isolates recovered from Mexican
      patients using phenotypic and molecular characteristics. The identification of
      isolates was assessed by internal transcribed spacer (ITS rDNA) sequencing. In
      vitro susceptibility to amphotericin B, fluconazole, voriconazole, posaconazole,
      caspofungin, anidulafungin and micafungin was determined according to Clinical
      and Laboratory Standards Institute (CLSI) procedures. Three isolates (07-2239, 11
      2242 and 04-2673) were used to induce systemic infection in immunocompetent ICR
      mice. Survival and tissue burden studies were used as markers of pathogenicity.
      All of the strains were resistant to every antifungal tested with MIC's for AmB
      (8->8 ug/ml), VRC (16->16 ug/ml), PSC (16->16 ug/ml), FLC (64->64 ug/ml) and
      echinocandins with MICs >=8 ug/ml. One hundred, ninety and sixty percent of the
      infected mice with the strains 07-2239, 11-2242 and 04-2673 died during the
      study, respectively. Regarding tissue burden, the highest fungal load of the
      infected mice was detected in brain followed by spleen and kidney, regardless of
      the strain.

PMID- 28456869
TI  - Fatty Acid Characterization and Biodiesel Production by the Marine Microalga
      Asteromonas gracilis: Statistical Optimization of Medium for Biomass and Lipid
      Enhancement.
AB  - Lipid production is an important indicator for evaluating microalgal species for
      biodiesel production. In this study, a new green microalga was isolated from a
      salt lake in Egypt and identified as Asteromonas gracilis. The main parameters
      such as biomass productivity, lipid content, and lipid productivity were
      evaluated in A. gracilis, cultivated in nutrient-starved (nitrogen, phosphorous),
      and salinity stress as a one-factor-at-a-time method. These parameters in general
      did not vary significantly from the standard nutrient growth media when these
      factors were utilized separately. Hence, response surface methodology (RSM) was
      assessed to study the combinatorial effect of different concentrations of the
      abovementioned factor conditions and to maximize the biomass productivity, lipid
      content, and lipid productivity of A. gracilis by determining optimal
      concentrations. RSM optimized media, including 1.36 M NaCl, 1 g/L nitrogen, and
      0.0 g/L phosphorus recorded maximum biomass productivity, lipid content, and
      lipid productivity (40.6 mg/L/day, 39.3%, and 15.9 mg/L/day, respectively) which
      agreed well with the predicted values (40.1 mg/L/day, 43.6%, and 14.6 mg/L/day,
      respectively). Fatty acid profile of A. gracilis was composed of C16:0, C16:1,
      C18:0, C18:3, C18:2, C18:1, and C20:5, and the properties of fuel were also in
      agreement with international standards. These results suggest that A. gracilis is
      a promising feedstock for biodiesel production.

PMID- 28456870
TI  - Protocol for motor and language mapping by navigated TMS in patients and healthy
      volunteers; workshop report.
AB  - INTRODUCTION: Navigated transcranial magnetic stimulation (nTMS) is increasingly
      used for preoperative mapping of motor function, and clinical evidence for its
      benefit for brain tumor patients is accumulating. In respect to language mapping
      with repetitive nTMS, literature reports have yielded variable results, and it is
      currently not routinely performed for presurgical language localization. The aim
      of this project is to define a common protocol for nTMS motor and language
      mapping to standardize its neurosurgical application and increase its clinical
      value. METHODS: The nTMS workshop group, consisting of highly experienced nTMS
      users with experience of more than 1500 preoperative nTMS examinations, met in
      Helsinki in January 2016 for thorough discussions of current evidence and
      personal experiences with the goal to recommend a standardized protocol for
      neurosurgical applications. RESULTS: nTMS motor mapping is a reliable and
      clinically validated tool to identify functional areas belonging to both normal
      and lesioned primary motor cortex. In contrast, this is less clear for language
      eloquent cortical areas identified by nTMS. The user group agreed on a core
      protocol, which enables comparison of results between centers and has an
      excellent safety profile. Recommendations for nTMS motor and language mapping
      protocols and their optimal clinical integration are presented here. CONCLUSION:
      At present, the expert panel recommends nTMS motor mapping in routine
      neurosurgical practice, as it has a sufficient level of evidence supporting its
      reliability. The panel recommends that nTMS language mapping be used in the
      framework of clinical studies to continue refinement of its protocol and increase
      reliability.

PMID- 28456872
TI  - Catechol-O-Methyltransferase (COMT): An Update on Its Role in Cancer,
      Neurological and Cardiovascular Diseases.
AB  - Catechol-O-methyltransferase (COMT) is an enzyme that catalyses the methylation
      of catechol substrates, classically in catecholamine metabolism, but also acting
      upon other substrates such as oestrogen and polyphenols. Although its classical
      function has been established for more than five decades, an ever expanding COMT
      role in other pathways and diseases has become a subject of active study in
      recent years. The most highlighted domains are related with COMT involvement in
      neuropsychiatric disorders and its role in the neurobiology of cognition,
      behaviour, emotions, pain processing and perception, sleep regulation, addictive
      behaviour and neurodegeneration. Nonetheless, great attention is also being
      devoted to a possible COMT contribution to the development of cardiovascular
      disorders and hormonally influenced diseases, including cancer. This review aims
      to update the role of COMT function and its involvement in cardiovascular and
      neurological disorders.

PMID- 28456871
TI  - Trends in non-help-seeking for mental disorders in Germany between 1997-1999 and
      2009-2012: a repeated cross-sectional study.
AB  - PURPOSE: This study sought to examine trends in non-help-seeking for mental
      disorders among persons with a prevalent mental disorder (12-month prevalence) in
      Germany between 1997-1999 and 2009-2012. METHODS: We examined data from 1909
      persons aged 18-65 years who participated in two independent, repeated cross
      sectional surveys (German National Interview and Examination Study 1997-1999,
      German Health Interview and Examination Survey for Adults 2009-2012) conducted 12
      years apart. Prevalent mental disorders (12-month prevalence) were determined
      using the Composite International Diagnostic Interview, which included
      information on lifetime help-seeking for mental health problems. Correlates of
      self-reported help-seeking were analyzed according to Andersen's Behavioral
      Model. Multivariable Poisson regression models were used to assess time trends in
      the directly standardized and model-adjusted prevalence of non-help-seeking
      across strata of socio-economic and clinical variables. RESULTS: The proportion
      of people with a prevalent mental disorder who have never sought help in their
      lifetime decreased significantly from 62% (95% CI 58.7-64.7) to 57% (95% CI 52.2
      60.9) between 1997-1999 and 2009-2012 in adults aged 18-65 years in Germany.
      Downward trends in non-help-seeking occurred in all investigated strata and
      reached statistical significance in women, in people who were living alone,
      people with medium educational level, people living in middle-sized communities,
      people with non-statutory health insurance, smokers, and people with co-existing
      somatic conditions. CONCLUSION: Despite a downward trend over the course of 12
      years, a large proportion of people suffering from mental disorders are still not
      seeking treatment in Germany. Further efforts to increase uptake of help-seeking
      for mental disorders in hard-to-reach groups are warranted to continue this
      trend.

PMID- 28456873
TI  - Hospitalization Among Patients with Sarcoidosis: A Population-Based Cohort Study
      1987-2015.
AB  - PURPOSE: There is little information about healthcare utilization for
      sarcoidosis. This study examined need for hospitalization as a measure of
      healthcare burden in this disease. METHODS: A cohort of Olmsted County, Minnesota
      residents diagnosed with sarcoidosis between January 1, 1976 and December 31,
      2013 was identified using the resources of the Rochester Epidemiology Project.
      Diagnosis was made based on individual medical record review. For each
      sarcoidosis subject, one sex- and age-matched comparator without sarcoidosis was
      randomly selected from the same population. Data on hospitalizations were
      retrieved electronically from billing data of the Mayo Clinic, the Olmsted
      Medical Center, and their affiliated hospitals. These data were available from
      1987 to 2015. Subjects who died or emigrated from Olmsted County prior to 1987
      were excluded. RESULTS: 332 incident cases of sarcoidosis and 342 comparators
      were included. Hospitalization rates were significantly higher among patients
      with sarcoidosis than comparators [rate ratio (RR) 1.37; 95% confidence interval
      (CI) 1.24-1.52]. Analysis based on sex revealed a significantly increased rate
      among females (RR 1.60; 95% CI 1.40-1.82) but not among males (RR 1.06; 95% CI
      0.91-1.25). The overall age- and sex-adjusted rates of hospitalization were
      stable from 1987 to 2015 for both cases and comparators. The average length of
      stay was similar (4.6 and 4.4 days for sarcoidosis and non-sarcoidosis
      hospitalizations, respectively, p = 0.87). CONCLUSION: In this population,
      patients with sarcoidosis had a significantly higher rate of hospitalization than
      patients without sarcoidosis, driven by higher rates in females.

PMID- 28456875
TI  - Erratum to Recombinant Factor XIII Reduces Severe Pleural Effusion in Children
      after Open-Heart Surgery.

PMID- 28456874
TI  - Pulmonary Artery Dimensions as a Prognosticator of Transplant-Free Survival in
      Scleroderma Interstitial Lung Disease.
AB  - BACKGROUND: Systemic sclerosis is a chronic debilitating autoimmune disease
      characterized by endothelial dysfunction and multi-organ fibrosis. Interstitial
      lung disease, a common manifestation of SSc, is termed scleroderma-related
      interstitial lung disease (SSc-ILD) and along with pulmonary hypertension
      contributes to a majority of deaths in SSc. SSc-ILD patients frequently develop
      pulmonary hypertension, which prognosticates a poorer outcome. We investigated
      pulmonary artery dimensions as an outcome predictor in patients with SSc-ILD.
      METHODS: A retrospective chart review abstracting data from SSc-ILD patients
      evaluated at a large tertiary care center was performed. HRCT imaging was
      reviewed and pulmonary artery (PA) and ascending aorta (Ao) diameters were
      measured for calculation of the PA:Ao ratio. Additionally, demographics, vital
      signs, spirometric parameters, comorbidities, and mean pulmonary artery pressures
      were collected when available. Outcome analysis with lung transplant or death
      events within 4 years based on pulmonary artery size as well as PA:Ao ratio was
      performed. RESULTS: 70 SSc-ILD patients were identified. Mean pulmonary artery
      diameter and PA:Ao ratio was 31.17 and 1.07 mm, respectively. Patients with a
      pulmonary artery diameter >=32 mm had higher risk of lung transplantation or
      death (p < 0.001) within 4 years. Patients with a PA:Ao ratio >=1.1 also had
      higher risk of lung transplantation or death (p < 0.001) within 4 years.
      Unadjusted outcomes analyses also identified PA:Ao ratio >=1.1 as an independent
      outcome predictor (hazard ratio 3.30, p < 0.001). CONCLUSIONS/CLINICAL
      IMPLICATIONS: In SSc-ILD patients, a PA:Ao ratio >=1.1 is associated with higher
      risk of lung transplant or death. These data suggest that PA:Ao dimension may be
      used for prognostication in SSc-ILD.

PMID- 28456876
TI  - Seroprevalence of Brucella antibodies in camels in Katsina State, Nigeria.
AB  - A cross-sectional study was carried out to determine the status of Brucella
      infection in one-humped (Dromedary) camels in the North and Central senatorial
      districts of Katsina State, Nigeria. Nine hundred and eighty serum samples from
      live and slaughtered camels were tested. Modified Rose Bengal plate test (RBPT)
      and serum agglutination test (SAT) with ethylenediaminetetraacetic acid, (EDTA)
      were used as screening and standard tests, respectively. The prevalence of
      Brucella antibodies were 110 (11.2%) and 103 (10.5%) for RBPT and SAT,
      respectively. Of the 472 and 508 serum samples tested from the herds and
      abattoirs, respectively, 63 (13.3%) and 47 (9.3%) were positive by RBPT while 62
      (13.1%) and 41 (8.1%) were positive by SAT, respectively. Based on the results,
      it was concluded that Brucella antibodies were present in camels in the study
      area. Poor management practices and mixing of camels with other species of
      livestock as well as unrestricted movement of camels were proposed to be the
      reasons for the prevalence of the disease in the study area. In view of the
      public health importance of the disease, it is recommended that there is the need
      to develop a strategic plan to decrease spread of brucellosis in the study area.

PMID- 28456877
TI  - Diagnostic performance of a computer-assisted diagnosis system for bone
      scintigraphy of newly developed skeletal metastasis in prostate cancer patients:
      search for low-sensitivity subgroups.
AB  - PURPOSE: The computer-assisted diagnostic system for bone scintigraphy (BS)
      BONENAVI is used to evaluate skeletal metastasis. We investigated its diagnostic
      performance in prostate cancer patients with and without skeletal metastasis and
      searched for the problems. METHODS: An artificial neural network (ANN) value was
      calculated in 226 prostate cancer patients (124 with skeletal metastasis and 101
      without) using BS. Receiver operating characteristic curve analysis was performed
      and the sensitivity and specificity determined (cutoff ANN = 0.5). Patient's
      situation at the time of diagnosis of skeletal metastasis, computed tomography
      (CT) type, extent of disease (EOD), and BS uptake grade were analyzed. False
      negative and false-positive results were recorded. RESULTS: BONENAVI showed 82%
      (102/124) of sensitivity and 83% (84/101) specificity for metastasis detection.
      There were no significant differences among CT types, although low EOD and faint
      BS uptake were associated with low ANN values and low sensitivity. Patients
      showed lower sensitivity during the follow-up period than staging work-up. False
      negative lesions were often located in the pelvis or adjacent to it. They
      comprised not only solitary, faint BS lesions but also overlaying to urinary
      excretion. CONCLUSIONS: BONENAVI with BS has good sensitivity and specificity for
      detecting prostate cancer's osseous metastasis. Low EOD and faint BS uptake are
      associated with low sensitivity but not the CT type. Prostate cancer patients
      likely to have false-negative results during the follow-up period had a solitary
      lesion in the pelvis with faint BS uptake or lesions overlaying to urinary
      excretion.

PMID- 28456878
TI  - Evaluation of the environmental epidemiologic data and methodology for the air
      quality standard in Beijing.
AB  - To evaluate the relationship between exposure to air pollutants and respiratory
      emergency room visits, a generalized additive model (GAM) was used to analyze the
      exposure-effect relationship between air pollutants and respiratory emergency
      room visits. The results showed that NO2, SO2, and PM10 have positive
      relationships with respiratory disease. Concentration increases of 10 MUg/m3 in
      NO2, SO2, and PM10 corresponded to 3.90% (95%CI 3.56-4.25), 0.81% (95%CI -0.09
      1.72), and 0.64% (95%CI 0.55-0.74) increases in respiratory emergency room
      visits. In addition, there is a strong synergic effect of PM10 and NO2 on
      respiratory diseases. The threshold values of the national standard grade II
      limits used in Beijing should be adjusted. An appropriate standard could
      effectively promote a significant decline in respiratory room visits and would
      eventually be beneficial to air quality management in residential areas.

PMID- 28456879
TI  - Anti-inflammatory effect as a mechanism of effectiveness underlying the clinical
      benefits of pelotherapy in osteoarthritis patients: regulation of the altered
      inflammatory and stress feedback response.
AB  - The purpose of the present investigation was to evaluate whether an anti
      inflammatory effect together with an improvement of the regulation of the
      interaction between the inflammatory and stress responses underlies the clinical
      benefits of pelotherapy in osteoarthritis (OA) patients. This study evaluated the
      effects of a 10-day cycle of pelotherapy at the spa centre 'El Raposo' (Spain) in
      a group of 21 OA patients diagnosed with primary knee OA. Clinical assessments
      included pain intensity using a visual analog scale; pain, stiffness and physical
      function using the Western Ontario and McMaster Universities Arthritis Index; and
      health-related quality of life using the EuroQol-5D questionnaire. Serum
      inflammatory cytokine levels (IL-1beta, TNF-alpha, IL-8, IL-6, IL-10 and TGF
      beta) were evaluated using the Bio-Plex(r) Luminex(r) system. Circulating
      neuroendocrine-stress biomarkers, such as cortisol and extracellular 72 kDa heat
      shock protein (eHsp72), were measured by ELISA. After the cycle of mud therapy,
      OA patients improved the knee flexion angle and OA-related pain, stiffness and
      physical function, and they reported a better health-related quality of life.
      Serum concentrations of IL-1beta, TNF-alpha, IL-8, IL-6 and TGF-beta, as well as
      eHsp72, were markedly decreased. Besides, systemic levels of cortisol increased
      significantly. These results confirm that the clinical benefits of mud therapy
      may well be mediated, at least in part, by its systemic anti-inflammatory effects
      and neuroendocrine-immune regulation in OA patients. Thus, mud therapy could be
      an effective alternative treatment in the management of OA.

PMID- 28456880
TI  - Altered segregation between task-positive and task-negative regions in mild
      traumatic brain injury.
AB  - Changes in large-scale brain networks that accompany mild traumatic brain injury
      (mTBI) were investigated using functional magnetic resonance imaging (fMRI)
      during the N-back working memory task at two cognitive loads (1-back and 2-back).
      Thirty mTBI patients were examined during the chronic stage of injury and
      compared to 28 control participants. Demographics and behavioral performance were
      matched across groups. Due to the diffuse nature of injury, we hypothesized that
      there would be an imbalance in the communication between task-positive and
      Default Mode Network (DMN) regions in the context of effortful task execution.
      Specifically, a graph-theoretic measure of modularity was used to quantify the
      extent to which groups of brain regions tended to segregate into task-positive
      and DMN sub-networks. Relative to controls, mTBI patients showed reduced
      segregation between the DMN and task-positive networks, but increased functional
      connectivity within the DMN regions during the more cognitively demanding 2-back
      task. Together, our findings reveal that patients exhibit alterations in the
      communication between and within neural networks during a cognitively demanding
      task. These findings reveal altered processes that persist through the chronic
      stage of injury, highlighting the need for longitudinal research to map the
      neural recovery of mTBI patients.

PMID- 28456881
TI  - Haplotype analysis of IL-10 gene polymorphism in couples with spontaneous
      abortions and aborted fetuses.
AB  - Spontaneous abortion is the loss of pregnancy during an early gestational period.
      Interleukin-10 is an anti-inflammatory cytokine which plays an important role in
      successful pregnancy outcome. The aim of the study is to elucidate an association
      of IL-10 gene promoter polymorphisms (-1082G/A, -819 C/T, -592C/A) in spontaneous
      abortions from Telangana state of South India. The present population-based
      retrospective case-control triad study includes a total of 80 case families with
      spontaneous abortions and 100 control families with medically terminated
      pregnancies. Peripheral blood from all the couples and fetal tissues of <20 weeks
      of gestation were collected. Genotype analysis was carried out by a standard
      amplification refractory mutation system-polymerase chain reaction followed by
      agarose gel electrophoresis. The strength of the association between IL-10 gene
      promoter polymorphisms and spontaneous abortions were measured by odd ratios and
      their respective 95% confidence intervals. Haplotype analysis was carried out for
      the three polymorphisms to establish an association of specific haplotypes with
      spontaneous abortions. The increased frequency of AA genotype and A allele of 
      1082G/A, TT genotype and T allele of -819C/T, and AA genotype and A allele of 
      592C/A was observed in case fetuses and case mothers compared to their respective
      controls. Haplotype analysis revealed that A-C-A, G-C-A haplotypes in fetuses and
      haplotypes A-C-C, G-T-C, A-T-A, and G-C-A in mothers were associated with
      increased risk of spontaneous abortions. IL-10 gene promoter polymorphisms may
      act as a major genetic regulator in the etiology of spontaneous abortions with
      maternal genome imprinting effects.

PMID- 28456882
TI  - The NLRP3 and CASP1 gene polymorphisms are associated with developing of acute
      coronary syndrome: a case-control study.
AB  - The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro
      IL-1B and pro-IL-18 leading to the active cytokines, which play an important role
      in the development of the acute coronary syndrome (ACS). The aim of the present
      study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers
      of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene
      [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene
      [UTR'3 G37562-C (rs10754558)] were genotyped by 5' exonuclease TaqMan assays in a
      group of 617 patients with ACS and 609 control individuals. Under recessive
      model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of
      developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08-2.86, P
      Res  = 0.022). In the same way, under recessive model, the CASP1 A10370-G was
      associated with increased risk of ACS (OR = 1.75, 95% CI 1.07-2.85, P Res  =
      0.025). Moreover, under co-dominant, dominant, over-dominant, and additive
      models, the NLRP3 UTR'3 G37562-C was associated with a decreased risk of ACS (OR
      = 0.45, 95%CI 0.22-0.92, P Co-dom  = 0.006; OR = 0.61, 95%CI 0.44-0.84, P Dom  =
      0.002; OR = 0.67, 95%CI 0.48-0.94, P Over-dom  = 0.02; and OR = 0.65, 95%CI 0.50
      0.94, P Add  = 0.02, respectively). In summary, this study demonstrates that the
      G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with
      increased risk of developing ACS, whereas the UTR'3 G37562-C polymorphism of the
      NLRP3 gene is associated with a decreased risk of developing ACS in Mexican
      population.

PMID- 28456883
TI  - Gas-phase Reactivity of meta-Benzyne Analogs Toward Small Oligonucleotides of
      Differing Lengths.
AB  - The gas-phase reactivity of two aromatic carbon-centered sigma,sigma-biradicals
      (meta-benzyne analogs) and a related monoradical towards small oligonucleotides
      of differing lengths was investigated in a Fourier-transform ion cyclotron
      resonance (FT-ICR) mass spectrometer coupled with laser-induced acoustic
      desorption (LIAD). The mono- and biradicals were positively charged to allow for
      manipulation in the mass spectrometer. The oligonucleotides were evaporated into
      the gas phase as intact neutral molecules by using LIAD. One of the biradicals
      was found to be unreactive. The reactive biradical reacts with dinucleoside
      phosphates and trinucleoside diphosphates mainly by addition to a nucleobase
      moiety followed by cleavage of the glycosidic bond, leading to a nucleobase
      radical (e.g., base-H) abstraction. In some instances, after the initial
      cleavage, the unquenched radical site of the biradical abstracts a hydrogen atom
      from the neutral fragment, which results in a net nucleobase abstraction. In
      sharp contrast, the related monoradical mainly undergoes facile hydrogen atom
      abstraction from the sugar moiety. As the size of the oligonucleotides increases,
      the rate of hydrogen atom abstraction from the sugar moiety by the monoradical
      was found to increase due to the presence of more hydrogen atom donor sites, and
      it is the only reaction observed for tetranucleoside triphosphates. Hence, the
      monoradical only attacks sugar moieties in these substrates. The biradical also
      shows significant attack at the sugar moiety for tetranucleoside triphosphates.
      This drastic change in reactivity indicates that the size of the oligonucleotides
      plays a key role in the outcome of these reactions. This finding is attributed to
      more compact conformations in the gas phase for the tetranucleoside triphosphates
      than for the smaller oligonucleotides, which result from stronger stabilizing
      interactions between the nucleobases. Graphical Abstract ?.

PMID- 28456884
TI  - The psycho-sensory wake drive-a power source for power naps and other common
      sleep-wake phenomena: a hypothesis.
AB  - Power naps are extensively practiced worldwide and there exists ample
      documentation of their efficacy in reversing daytime sleepiness. The source of
      their efficacy, however, as well as the cause and manifestation of many other
      common sleep-wake phenomena, cannot be entirely explained by the most commonly
      accepted model of sleep-wake regulation, the two-process model of Borbely, which
      considers the drives of the circadian and homeostatic sleep processes only. When
      considering the causes and manifestations of these unexplained phenomena, there
      appears to be evidence of a wake-promoting drive that is independent of the
      circadian oscillator indicated in the two-process model of sleep-wake regulation.
      Although this posited secondary wake drive, herein referred to as the psycho
      sensory wake drive, is always active during the awake state, its strength
      unpredictably varies during a normal day and, therefore, cannot be incorporated
      into the prevalent two-process model by any current mathematical formula.
      However, a supplemental graphic model superimposing it on the drives of Process S
      and Process C can provides plausible and parsimonious explanations for many
      otherwise unexplainable sleep-wake phenomena and enables rational guidelines for
      their effective practical management.

PMID- 28456885
TI  - Impact of Three-Dimensional Laparoscopy in a Bariatric Surgery Program: Influence
      in the Learning Curve.
AB  - INTRODUCTION: 3D laparoscopy allows the surgeon to regain the sense of depth and
      improve accuracy. The aim of the study was to assess the impact of 3D in
      bariatric surgery. PATIENTS AND METHODS: A retrospective cohort study was
      conducted. All our patients who underwent bariatric surgery (sleeve gastrectomy
      (SG) or gastric bypass (GB)) between 2013 and 2016 were included. We compared 3D
      laparoscopy cohort and 2D laparoscopy cohort. Variables are as follows: age, sex,
      DM, hypertension, surgeon experience, and type of intervention. Comparisons of
      operative time, hospital stay, conversion, complications, reoperation, and exitus
      are completed. RESULTS: Three hundred twelve consecutive patients were included.
      56.9% of patients underwent GB and 43.1% SG. Global complications were 3.2%
      (fistula 2.5%, hemoperitoneum 0.3%, others 0.4%). One hundred four procedures
      were performed in the 3D cohort and 208 in the 2D cohort. The 2D cohort and 3D
      cohort were similar regarding the following: percentage of GB vs SG, age, gender,
      learning curve, diabetes mellitus 2, hypertension, and sleep apnea. The operating
      time and hospital stay were significantly reduced in the 3D cohort (144.07 +/-
      58.07 vs 172.11 +/- 76.11 min and 5.12 +/- 9.6 vs 7.7 +/- 13.2 days. It was the
      same when we stratified the sample by type of surgery or experience of the
      surgeon. Complications were reduced in the 3D cohort in the surgeries performed
      by novice surgeons (10.2 vs 1.8%, p = 0.034). CONCLUSIONS: The use of 3D
      laparoscopy in bariatric surgery in our center has helped reducing the operating
      time and hospital stay, and improving the safety of the surgery, either in GB or
      SG, being equally favorable in novice or more experienced surgeons.

PMID- 28456886
TI  - Mutations in GMPPB Presenting with Pseudometabolic Myopathy.
AB  - Mutations in the guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B
      (GMPPB) gene encoding a key enzyme of the glycosylation pathway have been
      described in families with congenital (CMD) and limb girdle (LGMD) muscular
      dystrophy with reduced alpha-dystroglycan (alpha-DG) at muscle biopsy.Patients
      typically display a combined phenotype of muscular dystrophy, brain
      malformations, and generalized epilepsy. However, a wide spectrum of clinical
      severity has been described ranging from classical CMD presentation to children
      with mild, yet progressive LGMD with or without intellectual disability. Cardiac
      involvement, including a long QT interval and left ventricular dilatation, has
      also been described in four cases.Two missense mutations in GMPPB gene, one novel
      and one already reported, have been identified in a 21-year-old man presenting
      with elevated CK (38,650 UI/L; normal values <150 UI/L) without overt muscle
      weakness. Major complaints included limb myalgia, exercise intolerance, and
      several episodes of myoglobinuria consistent with a form of metabolic myopathy.
      Muscle biopsy showed only minimal alterations, whereas a marked reduction of
      glycosylated alpha-DG was evident.This case further expands the phenotypic
      spectrum of GMPPB mutations and highlights the importance of exhaustive molecular
      characterization of patients with reduced glycosylation of alpha-DG at muscle
      biopsy.

PMID- 28456887
TI  - Heterogeneous Phenotypes in Lipid Storage Myopathy Due to ETFDH Gene Mutations.
AB  - We present six novel patients affected by lipid storage myopathy (LSM) presenting
      mutations in the ETFDH gene. Although the diagnosis of multiple acyl-coenzyme-A
      dehydrogenase deficiency (MADD) in adult life is difficult, it is rewarding
      because of the possibility of treating patients with carnitine or riboflavin,
      leading to a full recovery. In our patients, a combination of precipitating risk
      factors including previous anorexia, alcoholism, poor nutrition, and pregnancy
      contributed to a metabolic critical condition that precipitated the catabolic
      state.In the present series of cases, five novel mutations have been identified
      in the ETFDH gene. We propose clinical guidelines to screen patients with LSM due
      to different defects, in order to obtain a fast diagnosis and offer appropriate
      treatment. In such patients, early diagnosis and treatment as well as avoiding
      risk factors are part of clinical management.Specific biochemical studies are
      indicated to identify the type of LSM, such as level of free carnitine and acyl
      carnitines and studies or organic acidemia. Indeed, when a patient is
      biochemically diagnosed with secondary carnitine deficiency, a follow-up with
      appropriate clinical-molecular protocol and genetic analysis is important to
      establish the final diagnosis, since riboflavin can be supplemented with benefit
      if riboflavin-responsive MADD is present. In muscle biopsies, increased lipophagy
      associated with p62-positive aggregates was observed. The clinical improvement
      can be attributed to the removal of an autophagic block, which appears to be
      reversible in this LSM.

PMID- 28456888
TI  - Is there any relationship between quality of life and polysomnographically
      detected sleep parameters/disorders in stable myasthenia gravis?
AB  - It is known that quality of life in myasthenia gravis is positively correlated
      with subjective sleep quality, still no data is available regarding the
      relationship between QOL and polysomnographically detected sleep parameters and
      disorders. In this study, we tried to highlighten this relationship, by
      performing polysomnography. Sleep-related complaints were evaluated in face-to
      face interviews with 19 clinically stable MG patients and 26 healthy controls.
      During the interviews questionnaires assessing sleep quality, excessive daytime
      sleepiness, fatigue, depression, anxiety, and Turkish version of the MG-QOL 15
      item scale [(MG-QOL15(T)] were administered and then an overnight polysomnography
      was performed. Sleep disorders, especially obstructive sleep apnea and fatigue
      were higher, whereas subjective sleep duration was significantly lower, in
      patients than controls. Excessive daytime sleepiness and poor sleep quality were
      not different between patients and controls. Other than percentage of sleep stage
      III, which was negatively correlated with MG-QOL15(T) scores, neither other sleep
      parameters nor sleep disorders were correlated with MG-QOL15(T) scores. MG
      composite, subjective sleep duration, fatigue severity and Hamilton depression
      rating scale scores were found to be positively correlated with MG-QOL15(T)
      scores. It was shown that decreasing disease severity and enhancing psychological
      well-being will improve patients' quality of life. We recommend that our findings
      should be repeated in a large prospective cohort of MG patients.

PMID- 28456889
TI  - Childhood hereditary ataxias: experience from a tertiary referral university
      hospital in Turkey.
AB  - Hereditary ataxias are a group of genetic disorders that are progressive and
      heterogeneous. The purpose of this study was to develop a practical and time
      efficient approach to diagnosing childhood hereditary ataxias by analyzing
      characteristics and final diagnosis at a tertiary referral clinic for pediatric
      neurology. 196 patients admitted to the pediatric neurology department were
      included. The medical records were examined for demographic features,
      neurological, laboratory, electrophysiological, cranial imaging, and pathological
      findings, and for genetic studies. Patients were divided into two groups based on
      whether a final diagnosis was made. The undiagnosed and diagnosed groups
      consisted of 157 (81.1%) and 39 (19.9%) patients, respectively. The two groups
      differed in terms of levels of history of consanguineous marriage and mental and
      motor development before diagnosis, absence of deep tendon reflexes, and the
      presence of polyneuropathic changes detected by electromyelography (EMG),
      abnormal visual evoked potentials (VEPs), electroretinography (ERG), and muscle
      biopsy. To the best of our knowledge, this is the first study involving a large
      spectrum of diseases related to autosomal recessive ataxias in childhood in
      Turkey. One out of five patients with hereditary childhood ataxias can be
      diagnosed with clinical and laboratory and electrodiagnostic examination,
      especially with the help of imaging facilities, while genetic analysis is not
      possible for every child. Cranial magnetic resonance imaging followed by EMG
      provides the most important clues for the diagnosis of hereditary childhood
      ataxias.

PMID- 28456890
TI  - Expanding The Rubric of "Patient-Centered Care" (PCC) to "Patient and
      Professional Centered Care" (PPCC) to Enhance Provider Well-Being.
AB  - Burnout among physicians, nurses, and students is a serious problem in U.S.
      healthcare that reflects inattentive management practices, outmoded images of the
      "good" provider as selflessly ignoring the care of the self, and an overarching
      rubric of Patient Centered Care (PCC) that leaves professional self-care out of
      the equation. We ask herein if expanding PCC to Patient and Professional Centered
      Care (PPCC) would be a useful idea to make provider self-care an explicit part of
      mission statements, a major part of management strategies and institutional goal
      setting, and of educational programs. We offer several practical suggestions for
      PPCC implementation, including structuring healthcare systems so as to nurture
      professional meaning, integrity, and inter-personal reflective emotional
      processing as a buffer against burnout and as a key to better patient care. It
      should not bring into question the primacy of practitioner commitment to the good
      of patients, nor should it be taken to suggest in any way a shift in focus away
      from patients' values and respect for patient autonomy. PPCC asserts that the
      respect for patient's values and autonomous choices properly remains the ethical
      benchmark of modern healthcare systems, along with altruistic professional
      commitment to the optimal care of patients. However, it enunciates an explicit
      commitment to structuring systems that allow for and actively encourage the
      professional well-being and wellness upon which good patient care depends.

PMID- 28456891
TI  - cCMP and cUMP in Apoptosis: Concepts and Methods.
AB  - The cyclic nucleotides cAMP and cGMP are well-characterized second messenger
      molecules regulating many important intracellular processes, such as
      differentiation, proliferation, and apoptosis. The latter is a highly regulated
      process of programmed cell death wherein several regulatory proteins, like those
      belonging to the Bcl-2 family, are involved. The initiation of apoptosis is
      regulated by three different pathways: the intrinsic or mitochondrial, the
      extrinsic, and the ER stress pathway. Recently, it has been published that the
      pyrimidine cyclic nucleotides cCMP and cUMP also function as second messenger
      molecules, and additionally have an effect on apoptosis signaling pathways. cCMP
      induced PKA-independent apoptosis via the intrinsic and ER-stress pathway in S49
      mouse lymphoma cells, and cCMP as well as cUMP induced apoptosis in human HEL
      cells via the intrinsic pathway. However, in human K-562 cells, which are known
      to be multidrug-resistant, cCMP and cUMP had no effect. Summarized in this
      chapter are the initiation of apoptosis by cCMP and cUMP regarding the various
      apoptotic pathways, the enzymes involved in apoptosis, as well as the most
      relevant methods for the detection and examination of apoptosis and the
      corresponding signaling pathways.

PMID- 28456892
TI  - A mathematical model of histamine-mediated neural activation during acupuncture.
AB  - Acupoints (Xuewei) are the focus of acupuncture on the body in traditional
      Chinese medicine treatment. Mast and nerve cells share a perivascular location
      and are abundantly found at these acupoints. Both environmental factors and
      medical treatments (chemical and physical stimuli) can stimulate local mast cells
      (MCs) to degranulate and thus release histamine which then activates the nearby
      nerves and therefore contributes to a signal transmission from the peripheral to
      the central nervous system. In this paper, a mathematical model is constructed to
      describe the signaling pathways that originate from the cells located at an
      acupoint. We show that: (1) peripheral stimuli induce the release of histamine
      from MCs; (2) histamine excites receptors in primary sensory neurons and leads to
      membrane action potentials; (3) histamine released from MCs at an acupoint plays
      a key role in response to acupuncture. These results are consistent with
      experimental observations. Furthermore, this study may facilitate our
      understanding of the signal transmission process that occurs in response to
      peripheral stimuli as well as provide a useful modeling tool for quantitatively
      analyzing immune and acupuncture mechanisms that involve MCs.

PMID- 28456894
TI  - Arenimonas alkanexedens sp. nov., isolated from a frozen soil sample.
AB  - A novel facultatively anaerobic bacterium, designated strain LAM-WHM-D11T, was
      isolated from a frozen soil sample of China. Cells of strain LAM-WHM-D11T were
      observed to be Gram-stain negative, non-motile and rod-shaped. Colonies were
      yellowish, and circular with convex shape. Strain LAM-WHM-D11T was found to be
      able to grow at 4-40  degrees C (optimum 15  degrees C), pH 7.5-2.0 (optimum 9.5)
      and 0-2.5% NaCl (w/v) (optimum 1.5%). The 16S rRNA gene sequence similarity
      analysis showed that strain LAM-WHM-D11T is closely related to Arenimonas metalli
      CF5-1T (98.0%), Arenimonas aquaticum NA-09T (97.9%), Arenimonas donghaensis HO3
      R19T (95.6%) and Arenimonas aestuarii S2-21T (95.3%). The DNA-DNA hybridization
      values between the isolate and A. metalli CGMCC 1.10787T, A. aquaticum KACC
      14663T, A. donghaensis KACC 11381T were 41.0 +/- 1.7, 44.7 +/- 1.4 and 42.8 +/-
      1.2%, respectively. The genomic DNA G+C content was found to be 66.5 mol% as
      determined by the T m method. The major cellular fatty acids were identified as
      iso-C15:0 and iso-C16:0. The major isoprenoid quinone was identified as
      ubiquinone 8 (Q-8). The major polar lipids were found to be
      diphosphatidyglycerol, phosphatidylethanolamine, phosphatidylglycerol,
      phosphatidylmonomethylethanolamine, two phospholipids and five unidentified
      lipids. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics,
      strain LAM-WHM-D11T is concluded to represent a novel species within the genus
      Arenimonas, for which the name Arenimonas alkanexedens sp. nov. is proposed. The
      type strain is LAM-WHM-D11T (ACCC 19750T = JCM 30464T).

PMID- 28456893
TI  - Evaluation of carbonate apatite blocks fabricated from dicalcium phosphate
      dihydrate blocks for reconstruction of rabbit femoral and tibial defects.
AB  - This study aimed to evaluate in vivo behavior of a carbonate apatite (CO3Ap)
      block fabricated by compositional transformation via a dissolution-precipitation
      reaction using a calcium hydrogen phosphate dihydrate [DCPD: CaHPO4.2H2O] block
      as a precursor. These blocks were used to reconstruct defects in the femur and
      tibia of rabbits, using sintered dense hydroxyapatite (HAp) blocks as the
      control. Both the CO3Ap and HAp blocks showed excellent tissue response and good
      osteoconductivity. HAp block maintained its structure even after 24 weeks of
      implantation, so no bone replacement of the implant was observed throughout the
      post-implantation period in either femoral or tibial bone defects. In contrast,
      CO3Ap was resorbed with increasing time after implantation and replaced with new
      bone. The CO3Ap block was resorbed approximately twice as fast at the metaphysis
      of the proximal tibia than at the epiphysis of the distal femur. The CO3Ap block
      was resorbed at an approximately linear change over time, with complete
      resorption was estimated by extrapolation of data at approximately 1-1.5 years.
      Hence, the CO3Ap block fabricated in this study has potential value as an ideal
      artificial bone substitute because of its resorption and subsequent replacement
      by bone.

PMID- 28456895
TI  - Cannabis Use, Medication Management and Adherence Among Persons Living with HIV.
AB  - Cannabis is used to relieve nausea, trigger weight gain, and reduce pain among
      adults living with HIV; however, the relationship between its use and medication
      adherence and management is unclear. Participants (N = 107) were from an ongoing
      cohort study of community-dwelling HIV+ adults, stratified by cannabis (CB) use:
      HIV+/CB+ (n = 41) and HIV+/CB- (n = 66). CB+ participants either tested positive
      in a urine toxicology screen for THC or had a self-reported history of regular
      and recent use. HIV-status was provided by physician results and/or biomarker
      assessment. Adherence was measured via the Morisky scale and medication
      management was assessed via the Medication Management Test-Revised. After
      adjusting for gender, we found no association between cannabis use group and
      adherence nor medication management. The amount of cannabis used was also not
      associated with measures of adherence and management. Preliminary findings
      suggest that cannabis use may not adversely influence medication
      adherence/management among adults living with HIV.

PMID- 28456897
TI  - Erratum to: Entangling Relation of Micro RNA-let7, miRNA-200 and miRNA-125 with
      Various Cancers.

PMID- 28456896
TI  - The survival and prognosticators of peritoneal cytology-positive gastric cancer
      patients who received upfront gastrectomy and subsequent S-1 chemotherapy.
AB  - BACKGROUND: Upfront surgery and subsequent S-1 chemotherapy is frequently
      selected for peritoneal cytology-positive (CY1) gastric cancer patients without
      other distant metastases (CY1-only). The objective of this study was to confirm
      the efficacy of this strategy in clinical practice and to identify the risk
      factors associated with survival. METHODS: Overall survival (OS) and recurrence
      free survival (RFS) were examined in 36 CY1-only patients who underwent
      macroscopic curative resection followed by postoperative S-1 chemotherapy between
      January 2000 and June 2015. Univariate and multivariate analyses were performed
      using a Cox proportional hazards model to identify risk factors. RESULTS: The
      median OS was 22.3 months (95% confidence interval 18.7-31.0). When the OS was
      compared by a log-rank test, significant differences were observed in the status
      of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and
      multivariate analyses demonstrated that the status of pN3b was a significant
      independent risk factor for OS and RFS. The median OS in patients with
      pathological N0-N3a (pN0-N3a) was 31.0 months, while that in patients with pN3b
      was 18.2 months (P = 0.002). The median RFS in patients with pN0-N3a was 16.4
      months, while that in patients with pN3b was 7.9 months (P = 0.007). CONCLUSIONS:
      The present study confirmed the efficacy of postoperative S-1 chemotherapy for
      CY1-only gastric cancer patients who received upfront surgery. This strategy
      might be recommended as clinical practice for patients with CY1 disease but a
      more effective treatment should be established for CY1-positive patients,
      especially for those who are diagnosed with CY1 and pN3b disease.

PMID- 28456898
TI  - Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced
      Biliary Tract Cancer.
AB  - Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of
      cetuximab addition over chemotherapy. This is probably due to the lack of
      predictive biomarkers. The aim of this study was to explore possible predictive
      factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with
      cetuximab (250 mg/m2/week, loading dose: 400 mg/m2), gemcitabine (1000 mg/m2 on
      day 1 and 8), and capecitabine (1300 mg/m2/day on days 1-14). The objective
      response rate (ORR), progression-free (PFS) and overall survival (OS) and the
      adverse events (AEs) were evaluated. An exploratory analysis was performed to
      find possible predictive factors on clinicopathological characteristics, routine
      laboratory parameters and early AEs, which occurred within 2 months from the
      beginning of treatment. The ORR was 21%. The median PFS and OS were 34 (95% CI:
      24-40) and 54 (43-67) weeks, respectively. The most frequent AEs were skin
      toxicities. In univariate analysis performance status, previous stent
      implantation, thrombocyte count at the start of therapy, early neutropenia and
      skin rash statistically significantly influenced the ORR, PFS and/or OS. In
      multivariate Cox regression analysis only normal thrombocyte count at treatment
      start and early acneiform rash were independent markers of longer survival. In
      patients showing early skin rash compared to the others the median PFS was 39 vs.
      13 weeks and the median OS was 67 vs. 26 weeks, respectively. It is suggested
      that early skin rash can be used as a biomarker to select patients who would
      benefit from the treatment with cetuximab plus chemotherapy.

PMID- 28456899
TI  - Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin
      Deficient Cells.
AB  - Friedreich's ataxia is an inherited neurological disorder characterised by
      mitochondrial dysfunction and increased susceptibility to oxidative stress. At
      present, no therapy has been shown to reduce disease progression. Strategies
      being trialled to treat Friedreich's ataxia include drugs that improve
      mitochondrial function and reduce oxidative injury. In addition, stem cells have
      been investigated as a potential therapeutic approach. We have used siRNA-induced
      knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for
      Friedreich's ataxia. Knockdown of frataxin protein expression to levels detected
      in patients with the disorder was achieved, leading to decreased cellular
      viability, increased susceptibility to hydrogen peroxide-induced oxidative
      stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell
      proliferation and differentiation. Bone marrow stem cells are being investigated
      extensively as potential treatments for a wide range of neurological disorders,
      including Friedreich's ataxia. The potential neuroprotective effects of bone
      marrow-derived mesenchymal stem cells were therefore studied using our frataxin
      deficient cell model. Soluble factors secreted by mesenchymal stem cells
      protected against cellular changes induced by frataxin deficiency, leading to
      restoration in frataxin levels and anti-oxidant defences, improved survival
      against oxidative stress and stimulated both cell proliferation and
      differentiation down the Schwann cell lineage. The demonstration that mesenchymal
      stem cell-derived factors can restore cellular homeostasis and function to
      frataxin-deficient cells further suggests that they may have potential
      therapeutic benefits for patients with Friedreich's ataxia.

PMID- 28456900
TI  - NESSCA Validation and Responsiveness of Several Rating Scales in Spinocerebellar
      Ataxia Type 2.
AB  - Spinocerebellar ataxia type 2 (SCA2), caused by a CAG expansion (CAGexp) at
      ATXN2, has a complex clinical picture. While validated ataxia scales are
      available, comprehensive instruments to measure all SCA2 neurological
      manifestations are required. This study aims to validate the Neurological
      Examination Score for the assessment of Spinocerebellar Ataxias (NESSCA) to be
      used in SCA2 and to compare its responsiveness to those obtained with other
      instruments. NESSCA, SARA, SCAFI, and CCFS scales were applied in symptomatic
      SCA2 patients. Correlations were done with age at onset, disease duration,
      CAGexp, and between scales. Responsiveness was estimated by comparing deltas of
      stable to worse patients after 12 months, according to Patient Global Impression
      of change, and the area under the curve (AUC) of the Receiver Operating
      Characteristics curve of scores range. Eighty-eight evaluations (49 patients)
      were obtained. NESSCA had an even distribution and correlated with disease
      duration (r = 0.55), SARA (r = 0.63), and CAGexp (rho = 0.32): both explained 44%
      of NESSCA variance. Deltas (95% CI) after 1 year in stable and worse patients
      were only significantly different for SARA. NESSCA, SARA, SCAFI, and CCFS AUC
      were 0.63, 0.81, 0.49, and 0.48, respectively. NESSCA is valid to be used in
      SCA2. However, the only instrument that presented good responsiveness to change
      in 1 year was SARA. We suggest that NESSCA can be used as a secondary outcome in
      future trials in SCA2 due to the burden of neurological disabilities related to
      disease progression.

PMID- 28456901
TI  - What Do We Know About the Influence of the Cerebellum on Walking Ability?
      Promising Findings from Transcranial Alternating Current Stimulation.
AB  - Several cerebellar functions related to upper limb motor control have been
      studied using non-invasive brain stimulation paradigms. We have recently shown
      that transcranial alternating current stimulation (tACS) may be a promising
      approach in shaping the plasticity of cerebellum-brain pathways in a safe and
      effective manner. This study aimed to assess whether cerebellar tACS at different
      frequencies may tune M1-leg excitability and modify gait control in healthy human
      subjects. To this end, we tested the effects of different cerebellar tACS
      frequencies over the right cerebellar hemisphere (at 10, 50, and 300 Hz, besides
      a sham-tACS) on M1-leg excitability, cerebellum-brain inhibition (CBI), and gait
      parameters in a sample of 25 healthy volunteers. Fifty and 300 Hz tACS
      differently modified M1-leg excitability and CBI from both lower limbs, without
      significant gait perturbations. We hypothesize that tACS aftereffect may depend
      on a selective entrainment of distinct cerebellar networks related to lower limb
      motor functions. Therefore, cerebellar tACS might represent a useful tool to
      modulate walking training in people with cerebellum-related gait impairment,
      given that tACS may potentially reset abnormal cerebellar circuitries.

PMID- 28456902
TI  - Cerebellar Transcranial Direct Current Stimulation (ctDCS) Impairs Balance
      Control in Healthy Individuals.
AB  - The cerebellum plays an important role in the planning, initiation and stability
      of movements, as well as in postural control and balance. Modulation of neural
      regions underlying balance control may be a potential alternative to treat
      balance impairments in cerebellar patients. Transcranial direct current
      stimulation (tDCS) is a noninvasive and safe tool capable to modulate cerebellar
      activity. We aim to investigate the effects of cerebellar tDCS (ctDCS) on
      postural balance in healthy individuals. Fifteen healthy and right-handed
      subjects were submitted to three sessions of ctDCS (anodal, cathodal and sham),
      separated by at least 48 h. In each session, tests of static (right and left
      Athlete Single Leg tests) and dynamic balance (Limits of Stability test) were
      performed using the Biodex Balance System before and immediately after the ctDCS.
      The results revealed that cathodal ctDCS impaired static balance of healthy
      individuals, reflected in higher scores on overall stability index when compared
      to baseline for right (p = 0.034) and left (p = 0.01) Athlete Single Leg test. In
      addition, we found significant impairment for left Athlete Single Leg test in
      comparison to sham stimulation (p = 0.04). As far as we know, this is the first
      study that points changes on balance control after ctDCS in healthy individuals.
      This finding raises insights to further investigation about cerebellar modulation
      for neurological patients.

PMID- 28456904
TI  - Myocardial deformation in iron overload cardiomyopathy: speckle tracking imaging
      in a beta-thalassemia major population.
AB  - Traditional echocardiography is unable to detect neither the early stages of iron
      overload cardiomyopathy nor myocardial iron deposition. The aim of the study is
      to determine myocardial systolic strain indices in thalassemia major (TM), and
      assess their relationship with T2*, a cardiac magnetic resonance index of the
      severity of cardiac iron overload. 55 TM cases with recent cardiac magnetic
      resonance (CMR-T2*) underwent speckle tracking analysis to assess regional
      myocardial strains and rotation. The results were compared with a normal control
      group (n = 20), and were subsequently analyzed on the basis of the CMR-T2*
      values. Two TM groups were studied: TM with significant cardiac iron overload
      ("low" T2*, <=20 ms; n = 21), and TM with normal T2* values ("normal" T2*, >20
      ms; n = 34). TM patients show significant, uniform decrease in circumferential
      and radial strain (P < 0.05), and a remarkable reduction in end-systolic
      rotation, both global, and for all segments (P < 0.001). No significant
      differences were found between the low- and the normal T2* group either in
      regional strains and rotation or in standard echocardiographic and CMR
      parameters. Spearman's correlation coefficient shows no significant correlation
      between myocardial strains, rotation and cardiac T2* values. In conclusion, our
      results are in accordance with recent evidence that myocardial iron overload is
      not the only mechanism underlying iron cardiomyopathy in TM. Strain imaging can
      predict subclinical myocardial dysfunction irrespective of CMR-T2* values,
      although it cannot replace CMR-T2* in assessing cardiac iron overload. Finally,
      it might be useful to appropriately time cardioactive treatment.

PMID- 28456905
TI  - Versatile, robust, and efficient tractography with constrained higher-order
      tensor fODFs.
AB  - PURPOSE: Develop a multi-fiber tractography method that produces fast and robust
      results based on input data from a wide range of diffusion MRI protocols,
      including high angular resolution diffusion imaging, multi-shell imaging, and
      clinical diffusion spectrum imaging (DSI) METHODS: In a unified deconvolution
      framework for different types of diffusion MRI protocols, we represent fiber
      orientation distribution functions as higher-order tensors, which permits use of
      a novel positive definiteness constraint (H-psd) that makes estimation from noisy
      input more robust. The resulting directions are used for deterministic fiber
      tracking with branching. RESULTS: We quantify accuracy on simulated data, as well
      as condition numbers and computation times on clinical data. We qualitatively
      investigate the benefits when processing suboptimal data, and show direct
      comparisons to several state-of-the-art techniques. CONCLUSION: The proposed
      method works faster than state-of-the-art approaches, achieves higher angular
      resolution on simulated data with known ground truth, and plausible results on
      clinical data. In addition to working with the same data as previous methods for
      multi-tissue deconvolution, it also supports DSI data.

PMID- 28456906
TI  - The Epigenomic Landscape in Osteoarthritis.
AB  - PURPOSE OF REVIEW: Epigenomics has emerged as a key player in our rapidly
      evolving understanding of osteoarthritis. Historical studies implicated
      epigenetic alterations, particularly DNA methylation, in OA pathogenesis;
      however, recent technological advances have resulted in numerous epigenome-wide
      studies examining in detail epigenetic modifications in OA. The purpose of this
      article is to introduce basic concepts in epigenetics and their recent
      applications to the study of osteoarthritis development and progression. RECENT
      FINDINGS: Epigenetics describes three major phenomena: DNA modification via
      methylation, histone sidechain modifications, and short noncoding RNA sequences
      which work in concert to regulate gene transcription in a heritable fashion.
      Cartilage has been the most widely studied tissue in OA, and differential
      methylation of genes involved in inflammation, cell cycle, TGFbeta, and HOX genes
      have been confirmed several times. Bone studies suggest similar findings, and the
      intriguing possibility of epigenetic changes in subchondral bone during many OA
      processes. Multiple studies have demonstrated the involvement of certain
      noncoding RNAs, particularly miR-140, in OA development via modulation of key
      catabolic factors. Although much work has been done, much is still unknown.
      Future epigenomic studies will no doubt continue to widen our understanding of
      extraarticular tissues and OA pathogenesis, and studies in animal models may
      offer glimpses into epigenome alterations in the earliest stages of OA.

PMID- 28456907
TI  - Bispectral Index monitoring in cancer patients undergoing palliative sedation: a
      preliminary report.
AB  - INTRODUCTION: Continuous palliative sedation (PS) is currently titrated based on
      clinical observation; however, it is often unclear if patients are still aware of
      their suffering. The aim of this prospective study is to characterize the level
      of consciousness in patients undergoing PS using Bispectral Index (BIS)
      monitoring. PATIENTS AND METHODS: We enrolled consecutive patients with
      refractory symptoms requiring PS. We documented the level of sedation using
      Ramsay Sedation Scale (RSS) and BIS at 0, 2, 4, 6, 12, and 24 h during the first
      day of PS and examined their degree of association. Intravenous midazolam or
      propofol was titrated according to the sedation level. RESULTS: Twenty patients
      on PS were recruited and had BIS continuous monitoring. Delirium was the most
      frequent reason for PS (n = 15, 75%). The median time of sedation was 24.5 h
      (interquartile range 6-46). The average time to achieve the desired sedation
      level was 6 h, and dose titration was required in 80% of the cases. At baseline,
      14 (70%) patients were considered to be awake according to RSS (i.e., 1-3) and 19
      (95%) were awake according to BIS (i.e., >60%). This proportion decreased to 31
      and 56% at 4 h, 27% and 53 at 6 h, and 22 and 33% at 24 h. RS and BIS had
      moderate correlation (rho = -0.58 to -0.65); however, a small proportion of
      patients were found to be awake by BIS (i.e., >=60%) despite clinical observation
      (i.e., RSS 4-6) indicating otherwise. CONCLUSIONS: The BIS is a noninvasive,
      bedside, real-time continuous monitoring method that may facilitate the objective
      assessment of level of consciousness and dose titration in patients undergoing
      PS.

PMID- 28456908
TI  - Use of prophylactic growth factors and antimicrobials in elderly patients with
      cancer: a review of the Medicare database.
AB  - PURPOSE: Growth factors and antimicrobials can reduce complications of
      chemotherapy-induced myelosuppression. Their prophylactic use in elderly patients
      is important given the associated comorbidity in this age group. There is a
      developing trend by payers to include supportive care agents in chemotherapy care
      bundles, which could affect clinical practice. We examined whether the febrile
      neutropenia (FN) risk categories can be used to describe utilization in the
      Centers for Medicare & Medicaid fee-for-service system in older adults. METHODS:
      We conducted a retrospective cohort study using the Medicare 20% sample data to
      describe growth factor and antimicrobial use patterns in patients receiving
      chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL).
      RESULTS: The highest percentage of patients receiving granulocyte colony
      stimulating factor (GCSF) within the first 5 days of a chemotherapy cycle were on
      high-FN-risk regimens, particularly for cycle 1 (73.7%, breast cancer; 61.5%,
      NHL) and cycle 2 (75.9%, breast cancer; 77.5%, NHL). Chemotherapy regimens for
      lung cancer are less myelotoxic, and growth factor use was more likely with
      latter cycles. Antibiotic use was lower at 15% within a cycle and appeared to be
      in response to complications. CONCLUSION: Practitioners use GCSF and antibiotics
      for elderly patients treated with potentially toxic chemotherapy, while
      comorbidity burden plays a role for patients treated with less myelotoxic
      regimens. The complexity of these choices in clinical practice should be
      considered in the proposed reimbursement changes being piloted by Medicare and
      private insurance companies seeking treatment cost reductions, as altered use
      could affect safety and efficacy.

PMID- 28456909
TI  - Patients' and parents' views regarding supportive care in childhood cancer.
AB  - PURPOSE: Intensive therapies in pediatric malignancies increased survival rates
      but also occurrence of treatment-related morbidities. Therefore, supportive care
      fulfills an increasingly important role. In planning development of guidelines
      with incorporation of shared decision making, we noticed that little is known
      about the needs and preferences of patients and their parents. Our goals were
      therefore to investigate (1) which supportive care topics patients and parents
      regard as most important and (2) the preferred role they wish to fulfill in
      decision making. METHODS: This qualitative study consisted of three focus groups
      (two traditional, one online) with patients and parents of two Dutch pediatric
      oncology centers. Data were transcribed as simple verbatim and analyzed using
      thematic analysis. RESULTS: Eleven adolescent patients and 18 parents shared
      detailed views on various aspects of supportive care. Themes of major importance
      were communication between patient and physician (commitment, accessibility,
      proactive attitude of physicians), well-timed provision of information, and the
      suitability and accessibility of psychosocial care. In contrast to prioritized
      supportive care topics by medical professionals, somatic issues (e.g., febrile
      neutropenia) were infrequently addressed. Patients and parents preferred to be
      actively involved in decision making in selected topics, such as choice of
      analgesics and anti-emetics, but not in, e.g., choice of antibiotics.
      CONCLUSIONS: Children with cancer and parents were provided a valuable insight
      into their views regarding supportive care and shared decision making. These
      results have important implications towards improving supportive care, both in
      selecting topics for guideline development and incorporating preferences of
      patients and parents herein.

PMID- 28456910
TI  - Microbes and the Role of Antibiotic Treatment for Wheezy Lower Respiratory Tract
      Illnesses in Preschool Children.
AB  - PURPOSE OF REVIEW: Antibiotics are commonly used to treat wheezy lower
      respiratory tract illnesses in preschoolers, although these infections have been
      traditionally thought to be predominantly of viral origin. Our purpose is to
      review recent research pertaining to the role of antibiotics in lower respiratory
      tract illnesses and on subsequent asthma development, as well as the possible
      mechanisms of their effects. RECENT FINDINGS: Increasing evidence suggests that
      asthma pathogenesis is associated with events during infancy and early childhood,
      particularly respiratory tract infections. While viruses are frequently detected
      in children with lower respiratory tract infections, the presence of potentially
      pathogenic bacteria is also often detected and may play a role in asthma
      pathogenesis. Recent evidence suggests that use of macrolides, particularly
      azithromycin, may decrease the risk of and duration of lower respiratory tract
      illnesses and prevent future episodes in specific high-risk populations. Infants
      and preschoolers who have wheezy lower respiratory tract illnesses have a higher
      risk of asthma development. Alterations in the microbiome are thought to be
      influential. While several recent studies identify azithromycin as a therapeutic
      option in these illnesses, additional research is needed.

PMID- 28456911
TI  - QSAR based therapeutic management of M. tuberculosis.
AB  - Mycobacterium tuberculosis is responsible for severe mortality and morbidity
      worldwide but, under-developed and developing countries are more prone to
      infection. In search of effective and wide-spectrum anti-tubercular agents,
      interdisciplinary approaches are being explored. Of the several approaches used,
      computer based quantitative structure activity relationship (QSAR) have gained
      momentum. Structure-based drug design and discovery implies a combined knowledge
      of accurate prediction of ligand poses with the good prediction and
      interpretation of statistically validated models derived from the 3D-QSAR
      approach. The validated models are generally used to screen a small combinatorial
      library of potential synthetic candidates to identify hits which further
      subjected to docking to filter out compounds as novel potential emerging drug
      molecules to address multidrug-resistant tuberculosis. Several newer models are
      integrated to QSAR methods which include different types of chemical and
      biological data, and simultaneous prediction of pharmacological activities
      including toxicities and/or other safety profiles to get new compounds with
      desired activity. In the process, several newer molecules have been identified
      which are now being assessed for their clinical efficacy. Present review deals
      with the advances made in the field highlighting overall future prospects of the
      development of anti-tuberculosis drugs.

PMID- 28456912
TI  - The neurons expressing calcium-binding proteins in the amygdala of the guinea
      pig: precisely designed interface for sex hormones.
AB  - The generation of emotional responses by the amygdala is determined largely by
      the balance of excitatory and inhibitory inputs to its principal neurons. These
      responses are often sex-specific, and any imbalance in excitatory and/or
      inhibitory tones leads to serious psychiatric disorders which occur with
      different rates in men versus women. To investigate the neural basis of sex
      specific processing in the amygdala, relationships between the neurons expressing
      calbindin (CB), parvalbumin (PV) and calretinin (CR), which form in the amygdala
      main subsets of gamma-aminobutyric acid (GABA)-ergic inhibitory system, and
      neurons endowed with oestrogen alpha (ERalpha), oestrogen beta (ERbeta) or
      androgen (AR) receptors were analysed using double immunohistochemistry in male
      and female guinea pig subjects. The results show that in various nuclei of the
      amygdala in both sexes small subsets of CB neurons and substantial proportions of
      PV neurons co-express ERbeta, while many of the CR neurons co-express ERalpha.
      Both these oestrogen-sensitive populations are strictly separated as CB and PV
      neurons almost never co-express ERalpha, while CR cells are usually devoid of
      ERbeta. In addition, in the medial nucleus and some other neighbouring regions,
      there are non-overlapping subpopulations of CB and CR neurons which co-express
      AR. In conclusion, the localization of ERalpha, ERbeta or AR within subsets of
      GABAergic interneurons across diverse amygdaloid regions suggests that steroid
      hormones may exert a significant influence over local neuronal activity by
      directly modulating inhibitory tone. The control of inhibitory tone may be one of
      the mechanisms whereby oestrogen and androgen could modulate amygdala processing
      in a sex-specific manner. Another mechanism may be thorough steroid-sensitive
      projection neurons, which are most probably located in the medial and central
      nuclei.

PMID- 28456913
TI  - The Effect and Osteoblast Signaling Response of Trace Silicon Doping
      Hydroxyapatite.
AB  - It is commonly accepted that silicon-doped hydroxyapatite (HAp) can achieve good
      repair effects for both spinal fusion and bone defect filling. However, the
      underlying mechanism by which silicon aids such beneficial effects is still not
      fully understood. Herein, we report on silicon-doped hydroxyapatites with
      excellent biocompatibility to osteoblast cells and suggest the signaling pathway
      involved. Non-doped HAp and trace Si-doped HAp (Si/HAp) with Si concentration
      close to and higher than natural bones were synthesized (i.e., 32, 260, and 2000
      ppm Si). The composition, crystal lattice vibration pattern, and morphology of
      these samples are characterized by X-ray diffraction (XRD), Fourier transform
      infrared (FTIR), and SEM, respectively. Positive biological activities of these
      Si-doped HAp materials were demonstrated through a cytotoxicity study and with
      the MTT and alkaline phosphatase (ALP) activity assays. The Si-doped samples were
      not toxic to MC3T3-E1 cells. Indeed, osteoblast proliferation measurement
      illustrated that 2000 ppm Si-doped HAp increased osteoblast proliferation by
      about 1.6 times compared to non-doped HAp. The ALP assay also proves that the
      trace Si doping has the function to enhance cell proliferation and
      differentiation. The ALP assay showed that Si doping also enhanced cell
      differentiation. QRT-PCR results revealed that Si-doped HAp enhanced osteogenic
      differentiation of osteoblast cells by upregulating genes such as MAPK3, Fzd1,
      Wnt1, Lrp6, and BMP2. In conclusion, Si-doped HAp promotes osteoblast
      proliferation and differentiation by activating the Wnt/beta-catenin and MAPK
      signaling pathways. This work could provide useful information of the beneficial
      effects of silicon in human bones and provide clues as to the molecular mechanism
      of the promotive effect of Si-doped HAp biomaterials.

PMID- 28456915
TI  - Reversible Cerebral Vasoconstriction Syndrome: Recognition and Treatment.
AB  - OPINION STATEMENT: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare
      but increasingly recognized disorder with over 500 cases published in the
      literature. The condition is characterized by recurrent severe thunderclap
      headaches with or without other neurological symptoms and diffuse segmental
      narrowing of the cerebral arteries which is reversible within 3 months. RCVS may
      occur spontaneously but in over 50% of cases, it is associated with various other
      conditions, including vasoactive medications or illicit drugs and the post-partum
      state. One third to a half of cases develop hemorrhagic or ischemic brain lesions
      or a combination of both. Posterior reversible encephalopathy syndrome (PRES)
      often occurs in association with RCVS and the conditions are likely to share a
      common pathophysiology. The pathogenesis of RCVS remains uncertain but autonomic
      dysregulation, oxidative stress, and genetic predisposition are postulated.
      Significant differential diagnoses include subarachnoid hemorrhage (SAH) due to
      aneurysmal rupture, cervical artery dissection, and primary angiitis of the
      central nervous system (PACNS). Although there is no proven treatment, calcium
      channel antagonists including nimodipine and verapamil have been administered
      with reported reduction of headache intensity but without effect on the time
      course of cerebral vasoconstriction. Glucocorticoids have been reported as an
      independent predictor of worse outcome and should be avoided. The cornerstone of
      RCVS management remains largely supportive with bed rest and analgesics and
      removal of precipitating factors. Invasive neurointerventional techniques should
      be reserved for severe deteriorating cases. The condition is usually benign and
      self-limited and the majority of patients have a favorable outcome but around 5
      10% are left with permanent neurological deficits and rare cases may die. This
      review details the importance of the early recognition of this increasingly
      described condition and current treatment recommendations.

PMID- 28456916
TI  - Novel green PVA-fullerenol mixed matrix supported membranes for separating water
      THF mixtures by pervaporation.
AB  - This study focuses first on the preparation of mixed matrix supported membranes
      of polyvinyl alcohol (PVA) and low-hydroxylated fullerenol C60(OH)12 used to
      create water selective membranes and then on their pervaporation properties for
      the separation of water-THF mixtures. These novel supported PVA membranes
      containing nano-carbon particles were prepared to reach high membrane performance
      for further integration in a dehydration process, such as distillation coupled to
      pervaporation. The separation of water-THF mixtures was performed with the
      supported membranes over a wide range of water concentrations in the feed
      mixture, i.e., from the azeotrope range up to 30 wt%, to evaluate the performance
      and stability of the thin active layer. SEM was used to visualize the internal
      morphology of the membrane. The influence of temperature on the transport
      properties was also investigated. All the membranes were highly water selective
      and stable up to 30 wt% water in the feed. The best compromise of transport
      properties was obtained for the C60(OH)12(5%)-PVA supported composite membrane: a
      permeate enrichment of 99.3 +/- 0.3 wt% water and a flux of 0.25 +/- 0.02 kg/(m2
      h) for the separation of a mixture containing 5.7 wt% water and 94.3 wt%
      tetrahydrofuran (THF) at 30  degrees C. Considering its water stability, this
      supported membrane with a dense layer thinner than 2 MUm appears promising for
      use in hybrid industrial processes to upgrade solvents with a smaller
      environmental footprint than conventional methods.

PMID- 28456917
TI  - Macroinvertebrate community in relation to water quality and riparian land use in
      a substropical mountain stream, China.
AB  - Exploring how water quality and land use shape the benthic macroinvertebrate
      community composition is of widespread interest in biodiversity conservation and
      environmental management. In this study, we investigated the structures of
      benthic macroinvertebrate assemblages and their environmental controls in terms
      of water quality and riparian land use in the Jinshui River, China. We carried
      out three campaigns including wet season (August 2009), dry season (November
      2009), and normal season (April 2010) based on the hydrological regime in Jinshui
      basin. The result showed that macroinvertebrate assemblage variations were better
      explained by water quality factors than land use based on variance partitioning
      procedure. The land use of 2 km upstream from the sampling sites had explained
      more variation than that of the whole riparian zone in upstream catchment on
      macroinvertebrate community, and land use of 2 km upstream also had more
      interactions with water quality. Canonical correspondence analysis (CCA)
      indicated that the elements or nutrient of magnesium (Mn), selenium (Se),
      strontium (Sr), silicon (Si), dissolved inorganic nitrogen (DN), sulfur (S),
      total organic carbon (TOC), and total nitrogen (TN) in water exhibited a strong
      relationship with macroinvertebrate assemblages. However, the variance in water
      quality explained by land use was lower than that explained by water quality in
      rivers using redundancy analysis. Our study suggested that proximate factors
      (i.e., water quality) were more important to interpret the macroinvertebrate
      community compared to ultimate factors (i.e., land use) for macroinvertebrate
      assemblages in river system.

PMID- 28456918
TI  - The global contribution of energy consumption by product exports from China.
AB  - This paper presents a model to analyze the mechanism of the global contribution
      of energy usage by product exports. The theoretical analysis is based on the
      perspective that contribution estimates should be in relatively smaller sectors
      in which the production characteristics could be considered, such as the
      productivity distribution for each sector. Then, we constructed a method to
      measure the global contribution of energy usage. The simple method to estimate
      the global contribution is the percentage of goods export volume compared to the
      GDP as a multiple of total energy consumption, but this method underestimates the
      global contribution because it ignores the structure of energy consumption and
      product export in China. According to our measurement method and based on the
      theoretical analysis, we calculated the global contribution of energy consumption
      only by industrial manufactured product exports in a smaller sector per industry
      or manufacturing sector. The results indicated that approximately 42% of the
      total energy usage in the whole economy for China in 2013 was contributed to
      foreign regions. Along with the primary products and service export in China, the
      global contribution of energy consumption for China in 2013 by export was larger
      than 42% of the total energy usage.

PMID- 28456919
TI  - Genotoxic risk assessment in professionals working hairdressers area using buccal
      micronucleus assay, in Aydin City, Turkey.
AB  - The aim of this study was to determine the genotoxic risk of professional
      hairdressers in Aydin City, Turkey, through investigating the micronucleus
      frequencies in buccal mucosa epithelial cells. All the hairdresser working
      hairdresser area were included in the genotoxic risk group (GRG = 20) in Aydin
      City, Turkey. The control group (CG = 20) comprised healthy individuals matching
      the gender and age of the GRG. Buccal mucosal scraping from all the 40 subjects
      of GRG (10 women and 10 men) and CG (10 women and 10 men) was stained with Giemsa
      stain and observed under light microscope (*40) for the presence of micronuclei
      (M 10 N) and karyolysis, pyknosis, condensed chromatin, karyorrhexis, nuclear
      bud, and binucleates in the exfoliated epithelial cells. There are significance
      between the incidence of MN in GRG and CG (P = <0.005) using one-way ANOVA,
      Kolmogorov-Smirnov Z test, and Spearman Rank Correlation Tests.

PMID- 28456914
TI  - Intracellular B Lymphocyte Signalling and the Regulation of Humoral Immunity and
      Autoimmunity.
AB  - B lymphocytes are critical for effective immunity; they produce antibodies and
      cytokines, present antigens to T lymphocytes and regulate immune responses.
      However, because of the inherent randomness in the process of generating their
      vast repertoire of antigen-specific receptors, B cells can also cause diseases
      through recognizing and reacting to self. Therefore, B lymphocyte selection and
      responses require tight regulation at multiple levels and at all stages of their
      development and activation to avoid diseases. Indeed, newly generated B
      lymphocytes undergo rigorous tolerance mechanisms in the bone marrow and,
      subsequently, in the periphery after their migration. Furthermore, activation of
      mature B cells is regulated through controlled expression of co-stimulatory
      receptors and intracellular signalling thresholds. All these regulatory events
      determine whether and how B lymphocytes respond to antigens, by undergoing
      apoptosis or proliferation. However, defects that alter regulated co-stimulatory
      receptor expression or intracellular signalling thresholds can lead to diseases.
      For example, autoimmune diseases can result from altered regulation of B cell
      responses leading to the emergence of high-affinity autoreactive B cells,
      autoantibody production and tissue damage. The exact cause(s) of defective B cell
      responses in autoimmune diseases remains unknown. However, there is evidence that
      defects or mutations in genes that encode individual intracellular signalling
      proteins lead to autoimmune diseases, thus confirming that defects in
      intracellular pathways mediate autoimmune diseases. This review provides a
      synopsis of current knowledge of signalling proteins and pathways that regulate B
      lymphocyte responses and how defects in these could promote autoimmune diseases.
      Most of the evidence comes from studies of mouse models of disease and from
      genetically engineered mice. Some, however, also come from studying B lymphocytes
      from patients and from genome-wide association studies. Defining proteins and
      signalling pathways that underpin atypical B cell response in diseases will help
      in understanding disease mechanisms and provide new therapeutic avenues for
      precision therapy.

PMID- 28456920
TI  - Non-enhanced phytoextraction of cadmium, zinc, and lead by high-yielding crops.
AB  - Heavy metal soil contamination from mining and smelting has been reported in
      several regions around the world, and phytoextraction, using plants to accumulate
      risk elements in aboveground harvestable organs, is a useful method of
      substantially reducing this contamination. In our 3-year experiment, we tested
      the hypothesis that phytoextraction can be successful in local soil conditions
      without external fertilizer input. The phytoextraction efficiency of 15 high
      yielding crop species was assessed in a field experiment performed at the Litavka
      River alluvium in the Pribram region of Czechia. This area is heavily polluted by
      Cd, Zn, and Pb from smelter installations which also polluted the river water and
      flood sediments. Heavy metal concentrations were analyzed in the herbaceous
      plants' aboveground and belowground biomass and in woody plants' leaves and
      branches. The highest Cd and Zn mean concentrations in the aboveground biomass
      were recorded in Salix x fragilis L. (10.14 and 343 mg kg-1 in twigs and 16.74
      and 1188 mg kg-1 in leaves, respectively). The heavy metal content in woody
      plants was significantly higher in leaves than in twigs. In addition, Malva
      verticillata L. had the highest Cd, Pb, and Zn concentrations in herbaceous
      species (6.26, 12.44, and 207 mg kg-1, respectively). The calculated heavy metal
      removal capacities in this study proved high phytoextraction efficiency in woody
      species; especially for Salix * fragilis L. In other tested plants, Sorghum
      bicolor L., Helianthus tuberosus L., Miscanthus sinensis Andersson, and Phalaris
      arundinacea L. species are also recommended for phytoextraction.

PMID- 28456921
TI  - Assessment of environmentally friendly fuel emissions from in-use vehicle
      exhaust: low-blend iso-stoichiometric GEM mixture as example.
AB  - Gasoline-ethanol-methanol fuel blends were formulated with the same
      stoichiometric air-to-fuel ratio and volumetric energy concentration as any
      binary ethanol-gasoline blend. When the stoichiometric blends operated in a
      vehicle, the time period, injector voltage, and pressure for each fuel injection
      event in the engine corresponded to a given stoichiometric air-to-fuel ratio, and
      the load was essentially constant. Three low oxygen content iso-stoichiometric
      ternary gasoline-ethanol-methanol fuel blends were prepared, and the properties
      were compared with regular-type fuel without added oxygen. One of the ternary
      fuels was tested using a fleet of in-use vehicles for15 weeks and compared to
      neat gasoline without oxygenated compounds as a reference. Only a small number of
      publications have compared these ternary fuels in the same engine, and little
      data exist on the performance and emissions of in-use spark-ignition engines. The
      total hydrocarbon emissions observed was similar in both fuels, in addition to
      the calculated ozone forming potential of the tailpipe and evaporative emissions.
      In ozone non-attainment areas, the original purpose for oxygenate gasolines was
      to decrease carbon monoxide emissions. The results suggest that the strategy is
      less effective than expected because there still exist a great number of vehicles
      that have suffered the progressive deterioration of emissions and do not react to
      oxygenation, while new vehicles are equipped with sophisticated air/fuel control
      systems, and oxygenation does not improve combustion because the systems adjust
      the stoichiometric point, making it insensitive to the origin of the added excess
      oxygen (fuel or excess air). Graphical abstract Low level ternary blend of
      gasoline-ethanol-methanol were prepared with the same stoichiometric air-fuel
      ratio and volumetric energy concentration, based on the volumetric energy density
      of the pre-blended components. Exhaust and evaporative emissions was compared
      with a blend having no oxygen in a fleet of 12 in-use vehicles. Vehicles that had
      suffer a normal deterioration of emissions and do not react to oxygenation, and
      new vehicles with more sophisticated air/fuel control systems do not improve
      combustion.

PMID- 28456923
TI  - Penile fracture with bilateral corpus cavernosa tears and complete urethral
      disruption.

PMID- 28456922
TI  - Nutritional status after conversion from conventional to in-centre nocturnal
      hemodialysis.
AB  - INTRODUCTION: Recipients of conventional hemodialysis (CHD; 3-4 h/session, 3
      times/week) experience volume expansion and nutritional impairment which may
      contribute to high mortality. Prolongation of sessions with in-centre nocturnal
      hemodialysis (INHD; 7-8 h/session, 3 times/week) may improve clinical outcomes by
      enhancement of ultrafiltration and uremic toxin removal. MATERIALS AND METHODS:
      In this prospective cohort study, 56 adult patients who were receiving
      maintenance CHD for at least 90 days were assigned to CHD (patients who remained
      in CHD) and INHD (patients who switched to INHD) groups. Both groups were
      followed for 1 year divided into four 13-week quarters; post-dialysis weight and
      interdialytic weight gain (IDWG) were captured in each quarter. Repeated measures
      analysis of variance was used to calculate group main effect, time main effect or
      time-group interaction effect. RESULTS: Conversion to INHD was associated with a
      mean (95% confidence interval) change in IDWG of 0.5 (0.08, 1.2) kg as compared
      to -0.3 (-0.9, 0.1) kg in the CHD group (p < 0.01). In the INHD group, post
      dialysis weight (% of baseline pre-dialysis weight) decreased after conversion,
      reaching a nadir during the first 3 months (0.7%) and subsequently it gradually
      increased and returned to its baseline at the end of follow-up. A similar
      temporal trend was seen for serum creatinine but not serum N-terminal pro-brain
      natriuretic peptide (NT-proBNP) which is a marker of extracellular volume. The
      changes in serum albumin, prealbumin and hs-CRP were not different between the
      two groups. CONCLUSIONS: Conversion to INHD was associated with greater IDWG and
      relatively stable body mass. We speculate that this gain in weight reflects an
      increase in lean body mass following the change in dialysis modality, which can
      be concluded from the parallel increase in serum creatinine and the lack of
      increase in NT-proBNP.

PMID- 28456924
TI  - Genomic recombination in primate bocavirus: inconsistency and alternative
      interpretations.
AB  - Human bocavirus (HBoV) is a single-stranded DNA virus in Parvoviridae family,
      causing respiratory diseases in human. The recent identifications of genomic
      recombination among the four human bocavirus genotypes and related non-human
      primate bocaviruses have shed lights into the evolutionary processes underpinning
      the diversity of primate bocavirus. Among these reports, however, we found
      inconsistency and possible alternative interpretations of the recombination
      events. In this study, these recombination events were reviewed, and the related
      genome sequences were re-analysed, aiming to inform the research community of
      bocavirus with more consistent knowledge and comprehensive interpretations on the
      recombination history of primate bocavirus.

PMID- 28456925
TI  - Necessity and least infringement conditions in public health ethics.
AB  - The influential public health ethics framework proposed by Childress et al.
      includes five "justificatory conditions," two of which are "necessity" and "least
      infringement." While the framework points to important moral values, we argue it
      is redundant for it to list both necessity and least infringement because they
      are logically equivalent. However, it is ambiguous whether Childress et al. would
      endorse this view, or hold the two conditions distinct. This ambiguity has
      resulted in confusion in public health ethics discussions citing the Childress et
      al. framework, as demonstrated by debate between Resnik and Wilson and Dawson. We
      analyse this debate to resolve these ambiguities. Finally, we argue that the
      necessity/least infringement principle of the Childress et al. framework applies
      only in cases in which only one intervention is to be implemented to achieve one
      specific goal. In other cases, it is not essential to require that only the least
      infringing intervention be implemented.

PMID- 28456926
TI  - Prevalence of HLA-B27 in the general population and in patients with axial
      spondyloarthritis in Saudi Arabia.
AB  - The prevalence of HLA-B27 in the general population and in axial
      spondyloarthritis (axSpA) patients in Saudi Arabia is unknown. The aim of this
      study was to evaluate the prevalence of HLA-B27 in these two populations and
      describe the delay in diagnosis of axSpA patients. The prevalence of HLA-B27 in
      the general population was evaluated using cord blood and healthy organ
      transplant donor databases. Data from patients with axSpA were collected
      retrospectively from five centers. Ankylosing spondylitis (AS) was diagnosed
      based on a positive X-ray, as evaluated by two independent readers. Patients with
      inflammatory bowel disease and psoriasis were excluded. A total of 134 axSpA
      patients were included, of whom 107 (79.9%) had AS, and most (67.2%) were males.
      HLA-B27 was positive in 60.4, 69, and 25.9% of patients with axSpA, AS, and non
      radiographic axSpA (nr-axSpA), respectively. The median and interquartile range
      (IQR) ages at symptom onset and disease diagnosis were 26 (20-33) and 30 (25-38)
      years, respectively. The median delay to diagnosis was 3 (1-6) years. There was a
      negative correlation between the time of onset of symptoms and the delay in
      diagnosis (r = -0.587). Male gender and HLA-B27 positivity were associated with a
      younger age at symptom onset/diagnosis (p < 0.05). HLA-B27 was positive in
      82/3332 (2.5%) and 27/1164 (2.3%) individuals in the cord blood and healthy organ
      transplant donor databases, respectively. The prevalence of HLA-B27 is lower in
      the general Saudi population and in axSpA patients compared to Caucasians, thus,
      limiting its utility as a diagnostic criterion.

PMID- 28456928
TI  - Pro-Inflammatory Cytokines in Psychiatric Disorders in Children and Adolescents:
      A Review.
AB  - Cytokines are a large group of small proteins which play a significant role in
      cell signaling and regulate a variety of processes in organisms, including
      proliferation and differentiation of many cells, mediation in defense reactions
      and regulation of hematopoiesis. Cytokines can be divided into those with pro-
      and those with anti-inflammatory properties. In the group of pro-inflammatory
      cytokines the most important are: IL-1 beta, IL-6, TNF-alpha, and IFN-gamma. Pro
      inflammatory cytokines might be involved in the pathophysiology of many
      psychiatric conditions in adults, but their role in children and adolescents is
      less clear. The aim of this article is to demonstrate the patterns of pro
      inflammatory cytokines in children and adolescents.

PMID- 28456927
TI  - Associations of three-dimensional T1 rho MR mapping and three-dimensional T2
      mapping with macroscopic and histologic grading as a biomarker for early
      articular degeneration of knee cartilage.
AB  - T1 rho and T2 mapping are magnetic resonance imaging (MRI) techniques to detect
      early degenerative changes in cartilage. Recent advancements have enabled 3D
      acquisition for both techniques. The objective of the present study was to
      examine the correlation of 3D T1 rho and 3D T2 mapping with macroscopic and
      histological characteristics of knee cartilage. Twenty-one patients who underwent
      total knee arthroplasty due to osteoarthritis with involvement of the medial
      compartment but with minimum involvement of the lateral compartment were
      enrolled. Prior to surgery, five series of MRI were acquired with a 3-T scanner.
      3D T1 rho/T2 analyses were performed following determination of regions to be
      assessed using in-house software that incorporated three series of MRI
      acquisitions data (3D-MERGE, 3D-SPGR, and 3D-CUBE). During surgery, the cartilage
      of the lateral compartment was macroscopically assessed with the International
      Cartilage Research Society (ICRS) articular classification system. The extracted
      specimens were histologically assessed using the OARSI histology score. Three
      regions of interest (ROI) were assessed for each slice (two slices per knee): the
      central lateral femoral condyle (cLFC), the posterior portion of the lateral
      femoral condyle (pLFC), and the lateral tibia plateau (LTP). For each ROI, the
      mean T1 rho and T2 relaxation time, the ICRS grade, and the OARSI score were
      compared. Neither the T1 rho nor the T2 reflected the macroscopic grading. The T1
      rho could discriminate between histological grades 1 and 2. However, the T2 could
      not. The T1 rho relaxation time was higher in the pLFC than in the cLFC even in
      the same grade. Compared to T2 mapping, T1 rho mapping may have an advantage in
      differentiating grades I and II cartilage degeneration on OARSI histological
      grading system.

PMID- 28456929
TI  - Carotid Intima-Media Thickness and Metabolic Syndrome Components in Obese
      Children and Adolescents.
AB  - Obesity in children and adolescents contributes to increased prevalence of
      metabolic and hemodynamic complications, which may impair endothelial function
      and structure. A high resolution B-mode ultrasound measurement of intima-media
      thickness (IMT) is a useful tool to assess early, preclinical stage of
      atherosclerosis. The objective of this study was to evaluate the carotid artery
      IMT in obese children and its association with insulin resistance and other
      traditional metabolic syndrome components. The study entailed 80 obese children,
      aged 5.3-17.9 year and a control group of 31 children. Obesity was defined using
      the International Obesity Task Force (IOTF) criteria. Metabolic syndrome was
      defined using the International Diabetes Federation (IDF) criteria of 2007. Each
      patient's anthropometric measurements, blood parameters, and the carotid IMT were
      evaluated. Insulin resistance indices were calculated. We found that children
      with metabolic syndrome had a significantly increased IMT compared to children
      who did not meet the syndrome criteria (0.62 +/- 0.09 mm vs. 0.55 +/- 0.18 mm, p
      = 0.03) and compared to control group (0.62 +/- 0.09 vs. 0.52 +/- 0.14, p =
      0.02). In a multivariable linear regression analysis, IMT correlated with
      systolic blood pressure (p = 0.005). The results did not show an association
      between IMT and insulin resistance. We conclude that abdominal obesity and the
      accompanying components of metabolic syndrome lead to increased carotid IMT. The
      enhanced systolic blood pressure plays a major role in changing the carotid IMT.

PMID- 28456930
TI  - Mortality Due to Nosocomial Infection with Klebsiella pneumoniae ESBL<sup/>.
AB  - Klebsiella pneumoniae is one of the most important hospital pathogens,
      particularly concerning the multidrug-resistant strain ESBL+. The aim of this
      study was to evaluate nosocomial infections with K. pneumoniae ESBL+ in the
      context of infection location, risk factors, and prognosis. This hospital study
      was conducted retrospectively and covered a 3 months' period. The infection with
      K. pneumoniae ESBL+ was diagnosed in 36 patients (19 women and 17 men) of the
      mean age of 74.2 +/- 14.8 years. The number of infected patients amounted to 2.2%
      of all patients admitted to Czerniakowski Hospital in Warsaw, Poland, over the
      study time. Twenty of these patients died (13 women and 7 men), representing 14%
      of all hospital deaths at the time. The infection with K. pneumoniae ESBL+
      occurred most frequently in the department of internal diseases, and rarely in
      neurology or intensive care wards. Bacteria was most often isolated from the
      urine, with the most distinct association between the use of urinary catheters
      and death (p = 0.019). We conclude that infections with K. pneumoniae ESBL+ were
      associated with over 55% mortality and usually occurred in the setting of
      internal diseases. Deaths due to K. pneumoniae ESBL+ infection were significantly
      related to the use of urinary bladder catheters.

PMID- 28456932
TI  - Synergistic Activity for Natural and Synthetic Inhibitors of Angiogenesis Induced
      by Murine Sarcoma L-1 and Human Kidney Cancer Cells.
AB  - Tumor angiogenesis is an important link in the process of tumor growth and
      metastasis. A number of substances with an anti-angiogenic activity has been
      described, but their efficiency remains low. Many researchers believe that a
      better therapeutic effect could be achieved using a cocktail of several anti
      angiogenic agents, having different points of action. A lot of synthetic and
      natural products of plant and animal origin have anti-tumor and anti-angiogenic
      properties. The aim of the present study was to evaluate the effect of some
      combinations of angiogenesis inhibitors on the growth and neovascularization of
      murine sarcoma L-1 , and on angiogenesis induced in the mouse skin by grafting of
      human renal cancer. The influence of theobromine, sulindac and its metabolite
      sulindac sulfone, chlorogenic acid, and shark liver oil on the afferent and
      efferent angiogenesis pathways was tested. Individually, all of these substances
      suppressed tumor growth and angiogenesis. Synergy was found for a combination of
      theobromine, sulindac, and chlorogenic acid (L-1 sarcoma tumor growth), and for
      theobromine with sulindac sulfone or with shark liver oil, which were given to
      the mice grafted with human renal cancer cells (angiogenesis). No synergistic
      effects were shown after preincubation with tumor cells and inhibitors.

PMID- 28456931
TI  - Thyroid Autoimmunity in Girls with Turner Syndrome.
AB  - Turner syndrome is associated with increased incidence of autoimmune diseases,
      especially those of the thyroid gland. The aim of this study was to assess the
      prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome.
      The study was retrospective and included 41 girls with Turner syndrome aged 6-18
      years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid
      peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and
      karyotype were investigated. The correlation between karyotype and incidence of
      thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for
      TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had
      subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out
      of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic
      karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the
      45,X karyotype. The study findings confirmed a high incidence of thyroid
      autoimmunity in girls with Turner syndrome, but we failed to observe an
      association between the incidence of thyroid autoimmunity and karyotype. We
      conclude that it is important to monitor thyroid function in patients with Turner
      syndrome because they are prone to develop hypothyroidism.

PMID- 28456933
TI  - Genetic Deletion of Kruppel-Like Factor 11 Aggravates Ischemic Brain Injury.
AB  - Kruppel-like factors (KLFs) belong to the zinc finger family of transcription
      factors, and their function in the CNS is largely unexplored. KLF11 is a member
      of the KLF family, and we have previously demonstrated that peroxisome
      proliferator-activated receptor gamma-mediated cerebral protection during
      ischemic insults needs recruitment of KLF11 as its critical coactivator. Here, we
      sought to determine the role of KLF11 itself in cerebrovascular function and the
      pathogenesis of ischemic stroke. Transient middle cerebral artery occlusion
      (MCAO) was performed in KLF11 knockout and wild-type control mice, and brain
      infarction was analyzed by TTC staining. BBB integrity was assessed by using
      Evans Blue and TMR-Dextran extravasation assays. KLF11 KO mice exhibited
      significantly larger brain infarction and poorer neurological outcomes in
      response to ischemic insults. Genetic deficiency of KLF11 in mice also
      significantly aggravated ischemia-induced BBB disruption by increasing
      cerebrovascular permeability and edema. Mechanistically, KLF11 was found to
      directly regulate IL-6 in the brains of ischemic mice. These findings suggest
      that KLF11 acts as a novel protective factor in ischemic stroke. Elucidating the
      functional importance of KLF11 in ischemia may lead us to discover novel
      pharmacological targets for the development of effective therapies against
      ischemic stroke.

PMID- 28456934
TI  - Lhx9 Is Required for the Development of Retinal Nitric Oxide-Synthesizing
      Amacrine Cell Subtype.
AB  - Amacrine cells are the most diverse group of retinal neurons. Various subtypes of
      amacrine interneurons mediate a vast majority of image forming and non-image
      forming visual functions. The transcriptional regulation governing the
      development of individual amacrine cell subtypes is not well understood. One such
      amacrine cell subtype comprises neuronal nitric oxide synthase (nNOS/bNOS/NOS1)
      expressing amacrine cells (NOACs) that regulate the release of nitric oxide (NO),
      a neurotransmitter with physiological and clinical implications in the retina. We
      have identified the LIM-homeodomain transcription factor LHX9 to be necessary for
      the genesis of NOACs. During retinal development, NOACs express Lhx9, and Lhx9
      null retinas lack NOACs. Lhx9-null retinas also display aberrations in dendritic
      stratification at the inner plexiform layer. Our cell lineage-tracing studies
      show that Lhx9-expressing cells give rise to both the GAD65 and GAD67 expressing
      sub-populations of GABAergic amacrine cells. As development proceeds, Lhx9 is
      downregulated in the GAD65 sub-population of GABAergic cells and is largely
      restricted to the GAD67 sub-population of amacrine cells that NOACs are a part
      of. Taken together, we have uncovered Lhx9 as a new molecular marker that defines
      a subset of amacrine cells and show that it is necessary for the development of
      the NOAC subtype of amacrine cells.

PMID- 28456936
TI  - Combination of High-Sensitivity C-Reactive Protein and Homocysteine Predicts the
      Post-Stroke Depression in Patients with Ischemic Stroke.
AB  - In this study, we examined the changes in high-sensitivity C-reactive protein (Hs
      CRP) and homocysteine (HCY) levels, two of the risk factors, during the acute
      period of ischemic stroke (IS) and evaluated the relationship between these two
      factors and long-term post-stroke depression (PSD). In this study, 259 patients
      with IS had finished the follow-up and were included. Based on the symptoms,
      diagnoses of depression were made in accordance with DSM-IV criteria for
      depression at 1 year after stroke. The influence of Hs-CRP/CHY levels on PSD was
      performed by binary logistic regression analysis and receiver operating
      characteristic curves (ROC). Totally, 94 out of the 259 patients were diagnosed
      as PSD (36.3%; 95% CI 30.4-42.1%). In multivariate logistic regression analysis,
      the third and fourth quartiles of Hs-CRP or HCY were significantly associated
      with PSD during the observation period compared to the first quartile group (P <
      0.05). In addition, patients with depression were older and more frequently were
      female, living with offspring, widowhood, higher initial stroke severity, and
      BMI. HCY improved the ability of Hs-CRP [0.72 (95% CI 0.66-0.79)] to diagnose PSD
      (AUC of the combined model 0.76; 95% CI 0.69-0.82; P = 0.021). The patient group
      with higher levels of both Hs-CRP and HCY (> median) had an OR of 6.05 (95 % CI
      3.13-10.15; P < 0.001) for PSD compared with patients with lower levels of both
      factors (< median). The data suggests that elevated serum levels of Hs-CRP and
      HCY were associated with the risk of developing PSD 1 year after the stroke
      onset, and those two factors combined to add prognostic information in the early
      evaluation of PSD.

PMID- 28456935
TI  - PROneurotrophins and CONSequences.
AB  - Proneurotrophins were initially thought to be simple inactive precursors, only
      responsible for promoting the folding of the mature domain and for the regulation
      of the neurotrophin secretory pathway. However, recent evidence shows that
      proneurotrophins can be secreted to the extracellular space, bind with high
      affinity to specific receptor complexes and induce activation of the apoptotic
      machinery with subsequent cell death of different neuronal populations. These
      pathways can be activated due to injury and to several neurodegenerative
      disorders, which promote proneurotrophin secretion to the extracellular space. In
      addition to neuropathology, extracellular proneurotrophins also play a pivotal
      role in many other cellular mechanisms in the nervous system. Proneurotrophins
      were shown to mediate synaptic plasticity, namely long-term depression in
      hippocampal neurons. They are also important in axonal development, and an
      increase of pro- to mature neurotrophin ratio has been described as a trigger of
      cell death. The conversion of proneurotrophins into the respective mature form is
      controlled by the action of several enzymes and regulators. The failure in this
      regulation is now considered one of the possible mechanisms responsible for
      pathological cell death associated to proneurotrophins. Here, we discuss the
      processes behind proneurotrophin action, with particular focus on proBDNF and
      proNGF and their regulatory pathways. Additionally, we review the most recent
      studies concerning proneurotrophin involvement in neuronal death, in several
      disease-associated states in the CNS and PNS, and discuss future avenues of
      investigation in the proneurotrophin field.

PMID- 28456937
TI  - Muscle Microdialysis to Investigate Inflammatory Biomarkers in
      Facioscapulohumeral Muscular Dystrophy.
AB  - Recent progresses in the understanding of facioscapulohumeral muscular dystrophy
      (FSHD) genetics opened the way to the development of targeted therapies. However,
      knowledge about pathophysiology of muscle damage is still limited and there is
      increasing need to identify biomarkers of disease activity in the perspective of
      clinical trial readiness.We analyzed inflammatory mediators in the interstitial
      fluid of muscles with different MRI signal in FSHD patients, comparing muscles
      displaying early lesions on short-tau inversion recovery (STIR) sequences with
      normal ones. Patients with one T1-weighted normal and STIR hyperintense (STIR+)
      and contralateral T1-weighted and STIR normal (STIR-) lower limb muscle were
      asked to enter the study. Twelve consecutive patients, five controls, and one non
      penetrant gene carrier underwent prolonged muscle microdialysis with high cut-off
      membranes. Microdialysates were analyzed using xMAP technology with a wide panel
      for cytokines, chemokines, and growth factors. A small number of inflammatory
      mediators were dysregulated in STIR+ versus STIR- and control muscles: CXCL13,
      upregulated in STIR+ muscles compared with controls (p < 0.01); CXCL5,
      downregulated in STIR+ compared with STIR- muscles (p < 0.05); and G-CSF,
      downregulated in STIR+ muscles compared with controls (p < 0.05). CXCL13 was also
      upregulated in the STIR+ muscles compared with the contralateral STIR- muscles of
      the same patient (p < 0.01).These results support the evidence of a selective
      inflammatory process taking place in STIR+ FSHD muscles. The application of
      microdialysis could provide insights on novel mechanisms involved in muscle
      damage in FSHD and in other myopathies. Further studies are needed to validate
      these investigated molecules as tissue and circulating biomarkers.

PMID- 28456938
TI  - Glioprotective Effect of Resveratrol: an Emerging Therapeutic Role for
      Oligodendroglial Cells.
AB  - Resveratrol is a natural polyphenol compound highly found in red wine that
      displays several beneficial effects on the central nervous system (CNS),
      preventing or slowing the progression of a wide variety of neurological diseases.
      Its neuroprotective role is particularly associated to modulation of antioxidant
      and anti-inflammatory responses in glial cells in a mechanism dependent of heme
      oxygenase 1 (HO-1) signaling pathway. Oligodendrocyte progenitor cells (OPC),
      primarily known for giving rise to mature oligodendrocytes, have emerged as
      dynamic cells that are also important to maintain the CNS homeostasis. In this
      sense, we have demonstrated that resveratrol has a protective effect on
      oligodendroglial functionality against lipopolysaccharide (LPS)-mediated
      cytotoxicity and that its glioprotective mechanism involves the nuclear factor
      erythroid 2-related factor 2 (Nrf2) and HO-1 pathways. LPS, through toll-like
      receptor 4 (TLR4), affected the release of trophic factors by OPC, including
      transforming growth factor beta (TGF-beta), brain-derived neurotrophic factor
      (BDNF), and glial cell-derived neurotrophic factor (GDNF), and resveratrol
      reestablished the trophic factor release to control levels. Additionally,
      resveratrol prevented the LPS-induced increase in the intracellular reactive
      oxygen species (ROS) as well as the decrease in glutathione (GSH) levels and in
      glutamate cysteine ligase (GCL) activity, through Nrf2/HO-1 signaling pathways.
      Resveratrol also prevented the increase of the transcriptional activities of
      nuclear factor kappaB (NFkappaB) and hypoxia-inducible factor 1 alpha (HIF
      1alpha) after LPS challenge. In summary, this is the first study showing the
      glioprotective effect of resveratrol on oligodendroglial cells.

PMID- 28456939
TI  - Genetic Mutation of GluN2B Protects Brain Cells Against Stroke Damages.
AB  - Immediately following ischemia, glutamate accumulates in the extracellular space
      and results in extensive stimulation of its receptors including N-methyl-D
      aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid
      (AMPA) receptors. A large amount of Ca2+ influx directly through the receptor
      gated ion channels which leads to Ca2+ overload and triggers several downstream
      lethal reactions. As a result, cell dies via apoptosis or necrosis, or both.
      Death-associated protein kinase 1 (DAPK1) physically and functionally interacts
      with the NMDA receptor GluN2B subunit at extra-synaptic sites and this
      interaction acts as a central mediator for stroke damage. The goal of this study
      is to explore an effective strategy in the treatment of stroke with a molecular
      genetic manipulation to interrupt DAPK1-GluN2B interaction. We generated a mutant
      strain of mice with the conditional deletion of GluN2B C-terminal tail consisting
      of amino acids 886-1269 in the forebrain excitatory neurons (the GluN2B mutant
      mice) and tested the protective effects of this mutation in stroke damages.
      GluN2B mutation effectively disrupted the DAPK1-GluN2B interaction and inhibited
      extra-synaptic NMDA receptor currents without affecting synaptic NMDA receptor
      channel activity in the central neurons. GluN2B mutation protected against stroke
      damages both in vitro and in vivo and hence improved behavioral performance.
      Disruption of the DAPK1-GluN2B interaction is therapeutically effective against
      stroke damages.

PMID- 28456940
TI  - MPTP Mouse Model of Preclinical and Clinical Parkinson's Disease as an Instrument
      for Translational Medicine.
AB  - Parkinson's disease (PD) is characterized by the appearance of motor symptoms
      many years after the onset of neurodegeneration, which explains low efficiency of
      therapy. Therefore, one of the priorities in neurology is to develop an early
      diagnosis and preventive treatment of PD, based on knowledge of molecular
      mechanisms of neurodegeneration and neuroplasticity in the nigrostriatal system.
      However, due to inability to diagnose PD at preclinical stage, research and
      development must be performed in animal models by comparing the nigrostriatal
      system in the models of asymptomatic and early symptomatic stages of PD. In this
      study, we showed that despite the progressive loss of neurons in the substantia
      nigra at the presymptomatic and symptomatic stage, almost no change was observed
      in the main functional characteristics of this brain region, including dopamine
      (DA) uptake and release, dopamine transporter (DAT) and vesicular monoamine
      transporter 2 (VMAT2) expression, and activity of MAO-A and MAO-B. In the
      striatum of presymptomatic mice, some parameters (DA release and uptake, MAO-A
      activity) remained compensatory unchanged or compensatory decreased (MAO-B gene
      expression and activity), while others-a reduction in DA levels in tissue and
      extracellular space and in VMAT2 and DAT expression-manifest the functional
      failure. In symptomatic mice, only a few parameters (spontaneous DA release and
      uptake, MAO-B gene expression and activity) remained at the same level as at
      presymptomatic stage, while most parameters (DA level in tissue and extracellular
      space, DA-stimulated release, VMAT2 and DAT contents), decreased, showing
      decompensation, which was enhanced by increasing MAO-A activity. Thus, this study
      provides a comprehensive assessment of the molecular mechanisms of
      neuroplasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine models of
      preclinical and clinical stages of PD, which could potentially serve as a
      powerful tool for translational medicine.

PMID- 28456941
TI  - Activation of Glucagon-Like Peptide-1 Receptor Promotes Neuroprotection in
      Experimental Autoimmune Encephalomyelitis by Reducing Neuroinflammatory
      Responses.
AB  - The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has
      been an important component in overcoming diabetes, and recent reports have
      uncovered novel beneficial roles of this signaling axis in central nervous system
      (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral
      ischemia, accelerating processes for exendin-4 repositioning. Here, we studied
      whether multiple sclerosis (MS) could be a complement to the CNS disorders that
      are associated with the GLP-1/GLP-1R signaling axis. Both components of the
      signaling axis, GLP-1 and GLP-1R proteins, are expressed in neurons, astrocytes,
      and microglia in the spinal cord of normal mice. In particular, they are abundant
      in Iba1-positive microglia. Upon challenge by experimental autoimmune
      encephalomyelitis (EAE), an animal model of MS, the mRNA expression of both GLP-1
      and GLP-1R was markedly downregulated in EAE-symptomatic spinal cords, indicating
      attenuated activity of GLP-1/GLP-1R signaling in EAE. Such a downregulation
      obviously occurred in LPS-stimulated rat primary microglia, a main cell type to
      express both GLP-1 and GLP-1R, further indicating attenuated activity of GLP
      1/GLP-1R signaling in activated microglia. To investigate whether increased
      activity of GLP-1R has a therapeutic benefit, exendin-4 (5 MUg/kg, i.p.), a GLP
      1R agonist, was administered daily to EAE-symptomatic mice. Exendin-4
      administration to symptomatic EAE mice significantly improved the clinical signs
      of the disease, along with the reversal of histopathological sequelae such as
      cell accumulation, demyelination, astrogliosis, microglial activation, and
      morphological transformation of activated microglia in the injured spinal cord.
      Such an improvement by exendin-4 was comparable to that by FTY720 (3 mg/kg,
      i.p.), a drug for MS. The neuroprotective effects of exendin-4 against EAE were
      also associated with decreased mRNA expression of proinflammatory cytokines, such
      as interleukin (IL)-17, IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha,
      all of which are usually upregulated in injured sites of the EAE spinal cord.
      Interestingly, exendin-4 exposure similarly reduced mRNA levels of IL-1beta and
      TNF-alpha in LPS-stimulated microglia. Furthermore, exendin-4 administration
      significantly attenuated activation of NF-kappaB signaling in EAE spinal cord and
      LPS-stimulated microglia. Collectively, the current study demonstrates the
      therapeutic potential of exendin-4 for MS by reducing immune responses in the
      CNS, highlighting the importance of the GLP-1/GLP-1R signaling axis in the
      development of a novel therapeutic strategy for MS.

PMID- 28456944
TI  - Avelumab: First Global Approval.
AB  - Avelumab (Bavencio(r)) is an intravenously administered programmed cell death
      ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the
      biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly
      developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of
      various tumours. It has received accelerated approval in the USA for the
      treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric
      patients aged >=12 years. The marketing authorization application for avelumab in
      the treatment of mMCC is undergoing regulatory review in the EU, the biologics
      license application for avelumab in the treatment of urothelial carcinoma is
      undergoing priority review by the FDA, and avelumab is in various stages of
      development internationally for a variety of cancers. This article summarizes the
      milestones in the development of avelumab leading to this first approval for
      mMCC.

PMID- 28456943
TI  - The Potential Role of Fosfomycin in Neonatal Sepsis Caused by Multidrug-Resistant
      Bacteria.
AB  - The broad-spectrum activity of fosfomycin, including against multidrug-resistant
      (MDR) strains, has led to renewed interest in its use in recent years. Neonatal
      sepsis remains a substantial cause of morbidity and mortality at a global level,
      with evidence that MDR bacteria play an increasing role. The evidence for use of
      fosfomycin in neonatal subjects is limited. We summarise current knowledge of the
      pharmacokinetics and clinical outcomes for the use of fosfomycin in neonatal
      sepsis and issues specific to neonatal physiology. While fosfomycin has a broad
      range of coverage, we evaluate the extent to which it may be effective against
      MDR bacteria in a neonatal setting, in light of recent evidence suggesting it to
      be most effective when administered in combination with other antibiotics. Given
      the urgency of clinical demand for treatment of MDR bacterial sepsis, we outline
      directions for further work, including the need for future clinical trials in
      this at-risk population.

PMID- 28456942
TI  - Synaptic Dysfunction in Alzheimer's Disease: Abeta, Tau, and Epigenetic
      Alterations.
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized in
      the early stages by loss of learning and memory. However, the mechanism
      underlying these symptoms remains unclear. The best correlation between cognitive
      decline and pathological changes is in synaptic dysfunction. Histopathological
      hallmarks of AD are the abnormal aggregation of Abeta and Tau. Evidence suggests
      that Abeta and Tau oligomers contribute to synaptic loss in AD. Recently, direct
      links between epigenetic alterations, such as dysfunction in non-coding RNAs
      (ncRNAs), and synaptic pathologies have emerged, raising interest in exploring
      the potential roles of ncRNAs in the synaptic deficits in AD. In this paper, we
      summarize the potential roles of Abeta, Tau, and epigenetic alterations
      (especially by ncRNAs) in the synaptic dysfunction of AD and discuss the novel
      findings in this area.

PMID- 28456946
TI  - The future of social media in orthopedic surgery.

PMID- 28456945
TI  - Outcome of Triple Antiplatelet Therapy Including Cilostazol in Elderly Patients
      with ST-Elevation Myocardial Infarction who Underwent Primary Percutaneous
      Coronary Intervention: Results from the INTERSTELLAR Registry.
AB  - OBJECTIVES: Compared with dual antiplatelet therapy including aspirin and
      clopidogrel, triple antiplatelet therapy including cilostazol has a mortality
      benefit in patients with ST-segment elevation myocardial infarction. However,
      whether the mortality benefit persists in elderly patients is not clear. METHODS:
      From 2007 to 2014, 1278 patients with ST-segment elevation myocardial infarction
      who underwent primary percutaneous coronary intervention were retrospectively
      analyzed. The patients were divided into four groups by age (<75 or >=75 years;
      young and elderly, respectively) and antiplatelet strategy (triple or dual
      antiplatelet therapy). We compared the mortality rates between the triple and
      dual antiplatelet therapy groups. RESULTS: There were 1052 (male, 85%; mean age,
      56.3 +/- 10.4 years) patients in the young group and 241 (male, 52.7%; mean age,
      80.3 +/- 4.5 years) patients in the elderly group. In the young and elderly
      groups, 220 (20.9%) and 28 (12.3%) patients were treated with triple antiplatelet
      therapy. During a 1-year follow-up period, 80 patients died (4.2% in the young
      group vs. 15.5% in the elderly group). Kaplan-Meier survival analysis revealed
      that triple antiplatelet therapy was associated with a lower mortality rate in
      the young group (log-rank, p = 0.005). Although there were more angiographic high
      risk patients in the elderly group, similar mortality rates were reported (log
      rank, p = 0.803) without increased bleeding rates (1 vs. 3.6% in the elderly
      group, p = 0.217). CONCLUSIONS: Triple antiplatelet therapy might be a better
      antiplatelet regimen than dual antiplatelet therapy for patients with ST-segment
      elevation myocardial infarction. Although this benefit was strong in patients
      aged <75 years, no definite increase in major bleeding was seen for elderly
      patients (aged >=75 years).

PMID- 28456947
TI  - Physician Communication Practices as a Barrier to Risk-Based HPV Vaccine Uptake
      Among Men Who Have Sex with Men.
AB  - The Advisory Committee on Immunization Practices recommends that men who have sex
      with men (MSM) 26 years of age or younger be routinely vaccinated against HPV.
      For men outside of this risk-based population, the recommendation is routine
      vaccination until age 21. Thus, in order for this risk-based recommendation for
      MSM to be implemented, two distinct actions need to be completed during the
      clinical visit: (1) discuss recommendations for HPV vaccination with men and (2)
      assess sexual orientation to determine if a risk-based recommendation should be
      made. We assessed the degree to which physicians routinely discussed issues of
      sexual orientation and HPV vaccination with male patients 22-26 years old. We
      used data from a statewide representative sample of 770 primary care physicians
      practicing in Florida who were randomly selected from the American Medical
      Association Physician Masterfile. The analytic sample consisted of physicians who
      provided care to men 22-26 years old (N = 220). Response rate was 51%. Data
      collection took place in 2014 and analyses in 2016. Only 13.6% of physicians were
      routinely discussing both sexual orientation and HPV vaccination with male
      patients 22-26 years old, and approximately a quarter (24.5%) were not discussing
      either. Differences in these behaviors were found based on gender, Hispanic
      ethnicity, availability of HPV vaccine in clinic, HPV-related knowledge, and
      specialty. A minority of physicians in this sample reported engaging with these
      patients in ways that are mostly likely to result in recommendations consistent
      with current Advisory Committee on Immunization Practices guidelines.

PMID- 28456948
TI  - Advance Care Planning Communication: Oncology Patients and Providers Voice their
      Perspectives.
AB  - Advance care planning helps to ensure that patients' end-of-life preferences are
      understood and discussed with providers. It is an important component of patient
      centered care, particularly when patients are facing life-limiting illness. It
      also has ethical implications for providers, yet evidence suggests that these
      conversations are not always occurring, particularly in underserved populations.
      The aim of this study was to understand the challenges and personal beliefs
      regarding ACP through interviews with patients undergoing active cancer treatment
      and their oncology providers. This study took place at an urban, multispecialty
      cancer center in the mid-Atlantic region where approximately 1400 patients are
      treated each year. Findings revealed differences among both patients and
      providers in terms of their ACP knowledge, preferences, and practices. Overall,
      70% of patients were familiar with advance directives (100% of White patients and
      45.5% of Black patients), yet only 35% of them reported having completed one
      (55.6% of White patients and 18.2% of Black patients, although not statistically
      significant). Most providers (70%) held ACP conversations with patients with
      advanced illness only. They tended to make assumptions about the amount of
      information that patients desired and noted the significant challenges that were
      inherent with these types of conversations. Overall, ethical implications are
      inherent in ACP as patients are making medical decisions without always having
      necessary information. There are various reasons why providers may not supply
      information regarding potential outcomes and end-of-life planning and why
      patients may not request (or know to request) more medical information.

PMID- 28456949
TI  - Monitoring of Atg5-Independent Mitophagy.
AB  - Mitophagy is a mitochondrial quality control mechanism where damaged and surplus
      mitochondria are removed by autophagy. There are at least two different mammalian
      autophagy pathways: the Atg5-dependent conventional pathway and an Atg5
      independent alternative pathway; the latter is involved in the erythrocyte
      mitophagy. In this chapter we describe the various experimental approaches to
      assess Atg5-indepedndent mitophagy in mammalian cells.

PMID- 28456950
TI  - A Rapid Fluorescence Assay for Measuring Sphingosine-1-Phosphate Transporter
      Activity in Erythrocytes.
AB  - Sphingosine-1-phosphate (S1P) is an intercellular signaling molecule that is
      present in the plasma and plays an important role in recruiting lymphocytes from
      the thymus and secondary lymphoid organs. Erythrocytes are the most abundant
      cells in the blood and substantially contribute to the S1P supply in the plasma
      by releasing intracellularly synthesized S1P via an S1P transporter. Thus, the
      S1P transporter in erythrocytes is a potential target for immuno-suppressing
      drugs.In this chapter, we describe a rapid method for measuring the activity of
      the erythrocyte S1P transporter by using the fluorescent S1P analog, 7-nitro-2
      1,3-benzoxadiazol-4-yl (NBD)-labeled S1P. This method does not require
      chromatography performed with high-performance liquid chromatography, liquid
      chromatography-tandem mass spectrometry, or thin-layer chromatography methods.
      Furthermore, S1P transporter activity can be detected by measuring the increase
      in fluorescence intensity in the extracellular buffer without performing lipid
      extraction.

PMID- 28456951
TI  - S1P Synergizes with Wall Shear Stress and Other Angiogenic Factors to Induce
      Endothelial Cell Sprouting Responses.
AB  - Angiogenesis is the process of new blood vessel growth from pre-existing
      structures. During sprout initiation, endothelial cells (ECs) are activated by
      pro-angiogenic factors to degrade the basement membrane, migrate into the
      surrounding matrix, and form structures that anastomose to connect neighboring
      vessels. Sphingosine 1-phosphate (S1P) is a biologically active lysosphingolipid
      that is secreted by platelets and promotes angiogenesis under normal and
      pathological conditions by acting on ECs. In addition to biochemical factors, the
      endothelium is continuously subjected to mechanical forces in the form of wall
      shear stress (WSS) from fluid forces. Here, we describe an in vitro, three
      dimensional (3D) endothelial sprouting assay that is significantly enhanced by
      S1P, WSS, angiogenic growth factors (GFs), and fibronectin. This assay is
      assembled by seeding primary human endothelial cells onto 3D collagen matrices
      containing S1P and other pro-angiogenic factors. Once attached, physiological
      levels of WSS are applied to induce robust sprouting responses. This approach
      promotes the initiation of angiogenic sprouts stimulated by S1P, and allows the
      study of 3D sprouting of primary human endothelial cells induced in response to
      these physiological factors.

PMID- 28456952
TI  - Preparation of Scaffolds from Decellularized Testicular Matrix.
AB  - Biological scaffolds composed of extracellular matrix (ECM) are typically derived
      by processes that involve decellularization of tissues or organs. Here we
      describe a simple and robust methodology for the preparation of decellularized
      testicular matrix (DTM) scaffolds with minimal damage to the native three
      dimensional structure and tissue-specific ECM components. Such DTM scaffolds can
      help to gain a better insight into the molecular composition and function of
      testicular ECM and to develop new tissue engineering approaches to treat various
      types of male fertility disorders.

PMID- 28456953
TI  - Extracellular Matrix from Whole Porcine Heart Decellularization for Cardiac
      Tissue Engineering.
AB  - Decellularization of whole porcine hearts followed by recellularization with
      fully differentiated cells made from patient-specific human induced pluripotent
      stem cells (iPSCs) may provide the ultimate solution for patients with heart
      failure. Decellularization is the process of completely disrupting all cells and
      removing the cellular components (e.g., antigenic proteins, lipids, DNA) from
      organic tissue, leaving only the extracellular matrix (ECM). The
      decellularization of porcine hearts can be accomplished in 24 h and results in
      98% DNA removal with only 6 h of detergent exposure. Automatically controlling
      the pressure during decellularization reduces the detergent exposure time while
      still completely removing immunogenic cell debris.

PMID- 28456954
TI  - Clearance of Maternal RNAs: Not a Mummy's Embryo Anymore.
AB  - Until the zygotic genome is activated, early development relies on the products
      deposited by the mother. Once the zygotic genome starts to be transcribed, most
      maternal products are not needed anymore by the developing embryo. This
      emancipation from the maternal genome occurs during the Zygotic Genome Activation
      (ZGA). Although the process by which the maternal content is replaced with
      zygotic products differs from species to species, there is a common theme to all
      of them: maternal transcripts are actively degraded. Here, a review of how the
      degradation of maternal RNAs is regulated during early development and
      discussions on some computational tools that may be of use in this research area
      are outlined.

PMID- 28456955
TI  - Link of Zygotic Genome Activation and Cell Cycle Control.
AB  - The activation of the zygotic genome and onset of transcription in blastula
      embryos is linked to changes in cell behavior and remodeling of the cell cycle
      and constitutes a transition from exclusive maternal to zygotic control of
      development. This step in development is referred to as mid-blastula transition
      and has served as a paradigm for the link between developmental program and cell
      behavior and morphology. Here, we discuss the mechanism and functional
      relationships between the zygotic genome activation and cell cycle control during
      mid-blastula transition with a focus on Drosophila embryos.

PMID- 28456956
TI  - Role of MicroRNAs in Zygotic Genome Activation: Modulation of mRNA During
      Embryogenesis.
AB  - A fundamental process occurring during early development is the zygotic genome
      activation, i.e., the initiation of transcription from the embryonic genome.
      Before that step, cellular processes in the developing embryo are dictated by
      transcripts produced by the maternal genome and accumulated in the egg during
      oogenesis. The maternal-to-zygotic transition (MZT) involves both the clearance
      of maternal RNAs and the initiation of transcription of the embryonic genome and
      is a tightly regulated process. In some species, decay of maternal transcripts
      may be facilitated by the activity of microRNAs. These small RNAs can act
      pleiotropically, blocking translation and inducing destabilization of hundreds of
      different maternal targets. In this review, we will discuss the role of microRNAs
      during MZT, focusing on Drosophila melanogaster and vertebrate models, Xenopus
      laevis, Zebrafish and mouse, in which such a mechanism has been more extensively
      studied.

PMID- 28456957
TI  - Gene Expression Analysis in Mammalian Oocytes and Embryos by Quantitative Real
      Time RT-PCR.
AB  - This chapter describes methods for preparing oocytes and embryos to analyze their
      gene expression at specific developmental stages. We illustrate how to collect
      germinal vesicles (GVs) and mature metaphase II (MII) stage oocytes, as well as
      how to collect embryos at specific developmental stages from the pronucleus (PN)
      to the blastocyst stage from female mice. We also describe how to prepare mRNAs
      from these precious cells to analyze the expression of the target genes. The
      materials and methods in this chapter are used mainly for mouse oocytes and
      embryos, but with subtle modifications, they may be applicable for most mammalian
      species.

PMID- 28456958
TI  - Detection of miRNA in Mammalian Oocytes and Embryos.
AB  - MicroRNAs (miRNAs) play a crucial role in the regulation of many post
      transcriptional processes in reproductive cells. Regulation of maternal mRNA
      translation and activation of zygotic mRNA are essential to successful embryonic
      development. Moreover, the precise development of embryonic cell and/or tissue
      lineages requires temporal and spatial control of gene expression, mRNA
      abundance, and translation into proteins, which is in part regulated via miRNA.
      Here, we describe some key protocols that can be utilized to detect and quantify
      miRNA in in vitro produced oocytes and embryos.

PMID- 28456959
TI  - Detection of Bidirectional Promoter-Derived lncRNAs from Small-Scale Samples
      Using Pre-Amplification-Free Directional RNA-seq Method.
AB  - Development of high-throughput sequencing technologies has uncovered the
      immensity of the long noncoding RNA (lncRNA) world. Divergently transcribed
      lncRNAs from bidirectional gene promoters, called promoter-associated noncoding
      RNAs (pancRNAs), account for ~20% of the total number of lncRNAs, and this major
      fraction is involved in many biological processes, such as development and cancer
      formation. Recently, we have found that the pancRNAs activate their partner
      genes, as represented by the fact that pancIl17d, a pancRNA that is transcribed
      from the antisense strand of the promoter region of Interleukin 17d (Il17d) at
      the onset of zygotic gene activation (ZGA), is essential for mouse
      preimplantation development through Il17d upregulation. The discovery of the
      expression of a specific set of pancRNAs during ZGA was achieved by using a
      method that generates directional RNA-seq libraries from small-scale samples.
      Although there are several methods available for small-scale samples, most of
      them require a pre-amplification procedure that frequently generates some
      amplification biases toward a subset of transcripts. We provide here a highly
      sensitive and reproducible method based on the preparation of directional RNA-seq
      libraries from as little as 100 mouse oocytes or embryos without pre
      amplification for the quantification of lncRNAs as well as mRNAs.

PMID- 28456960
TI  - Detection and Characterization of Small Noncoding RNAs in Mouse Gametes and
      Embryos Prior to Zygotic Genome Activation.
AB  - Small noncoding RNAs (ncRNAs) are regulatory elements of gene expression in all
      cell types and tissues. An ever-increasing number of studies have implicated
      ncRNAs in differentiation and developmental processes. In mammals, as a
      consequence of fertilization, the content of ncRNAs in the zygote is mostly the
      result of the maternal material included on oocytes and the potential sperm-borne
      paternal contributions. The genetic identity program of any individual is the
      reprogramming of each parental contribution to the zygotic genome activation. In
      mouse, this activation occurs at 2-cell stage. In this program of early
      development the small ncRNAs can play important roles. Here, we describe
      protocols for collection of oocytes, spermatozoa, and zygotes in mouse, followed
      by RNA purification to analyze the different types of small ncRNA by next
      generation sequencing approaches (NGS). Bioinformatics protocols also describe
      the methodology able to characterize microRNAs (miRNAs) as the most well-known
      and widespread regulatory small ncRNA. The comparative analysis allows
      identifying the changes and background previous to zygotic genome activation.

PMID- 28456961
TI  - Purification of Zygotically Transcribed RNA through Metabolic Labeling of Early
      Zebrafish Embryos.
AB  - Early embryonic development in all known metazoans is characterized by a
      transcriptionally silent phase, during which development is under control of
      maternally loaded protein and RNA. The zygotic genome becomes transcriptionally
      active after a series of rapid reductive cleavage divisions. In this chapter, we
      present a method to metabolically label, purify, and analyze newly transcribed
      RNAs in early zebrafish embryos. We previously used this method, which is
      adaptable to other embryos and systems, to determine the onset of zygotic
      transcription activation and identify the first zygotic transcripts.

PMID- 28456962
TI  - RNA FISH to Study Zygotic Genome Activation in Early Mouse Embryos.
AB  - Characterizing the maternal-to-zygotic transition (MZT) is a central question in
      embryogenesis, and is critical for our understanding of early post-fertilization
      events in mammals. High-throughput RNA sequencing (RNA Seq) of mouse oocytes and
      early embryos has recently revealed that elaborate transcription patterns of
      genes and repeats are established post-fertilization. This occurs in the context
      of the gradually depleted maternal pool of RNA provided by the oocyte, which can
      confound the accurate analysis of the zygotic genome activation when the mRNA
      population is sequenced. In this context, and given the limited amounts of
      material available from embryos, particularly when studying mutants, as well as
      the cost of sequencing, an alternative, complementary single cell approach is RNA
      FISH. This approach can assay the expression of specific genes or genetic
      elements during preimplantation development, in particular during the MZT. Here,
      we describe how RNA FISH can be applied to visualize nascent transcription at
      specific genomic loci in embryos at different stages of preimplantation
      development and also discuss possible analytical methods of RNA FISH data.

PMID- 28456963
TI  - Detection of RNA Polymerase II in Mouse Embryos During Zygotic Genome Activation
      Using Immunocytochemistry.
AB  - Mammalian pre-implantation embryos represent a highly dynamic experimental model
      for comparative studies of nuclear structure and functions in the context of
      gradual reactivation of transcription. Here, we present details of the methods
      that allow localizing RNA polymerase II in mouse pre-implantation embryos with
      specific antibodies, using fluorescent/confocal and electron microscopy. We
      stress the special aspects of immunolabeling protocols in respect to the
      embryonic material. We made a special emphasis on the essential steps preceding
      the immunocytochemical experiments. In particular, we consider the procedures of
      female hormonal stimulation and embryo collection. The described approaches are
      also applicable to study other nuclear proteins.

PMID- 28456964
TI  - Immunological Staining of Global Changes in DNA Methylation in the Early
      Mammalian Embryo.
AB  - The structural complexity of chromatin can make antibody access to some nuclear
      antigens energetically unfavorable. This can limit the usefulness and reliability
      of immunostaining unless validated methods of epitope retrieval are applied. We
      found that denaturation of chromatin by sequential use of acidification and
      tryptic digestion of fixed cells is required to reliably detect DNA methylation
      in the embryo. Using this method to unmask the epitope revealed an unexpected
      pattern of reprogramming of global patterns of DNA methylation in the
      preimplantation embryo. This paper provides a detailed description of the
      procedures required for immunological detection of 5-methylcytosine in the early
      embryo.

PMID- 28456965
TI  - Single Cell Restriction Enzyme-Based Analysis of Methylation at Genomic Imprinted
      Regions in Preimplantation Mouse Embryos.
AB  - The methylation of cytosines in DNA is a fundamental epigenetic regulatory
      mechanism. During preimplantation development, mammalian embryos undergo
      extensive epigenetic reprogramming, including the global erasure of germ cell
      specific DNA methylation marks, to allow for the establishment of the pluripotent
      state of the epiblast. However, DNA methylation marks at specific regions, such
      as imprinted gene regions, escape this reprogramming process, as their
      inheritance from germline to soma is paramount for proper development. To study
      the dynamics of DNA methylation marks in single blastomeres of mouse
      preimplantation embryos, we devised a new approach-single cell restriction enzyme
      analysis of methylation (SCRAM). SCRAM allows for reliable, fast, and high
      throughput analysis of DNA methylation states of multiple regions of interest
      from single cells. In the method described below, SCRAM is specifically used to
      address loss of DNA methylation at genomic imprints or other highly methylated
      regions of interest.

PMID- 28456966
TI  - Use of Chemicals to Inhibit DNA Replication, Transcription, and Protein Synthesis
      to Study Zygotic Genome Activation.
AB  - Maternal-to-zygotic transition is an event that developmental control of early
      embryos is switched from oocyte-derived factors to the zygotic genome. Ability to
      inhibit DNA replication, transcription, and translation is an important tool in
      studying events, such as zygotic genome activation, during embyogenesis. Here, we
      describe approaches to block DNA replication, transcription, and translation
      using chemical inhibitors. Then we also demonstrate how the transcript level of a
      maternally inherited gene, ten-eleven translocation methylcytosine dioxygenase 3,
      responses to the chemical treatments.

PMID- 28456967
TI  - Targeted Gene Knockdown in Early Embryos Using siRNA.
AB  - RNA interference is a convenient and highly effective technique to investigate
      the biological function of genes. Adequately designed RNA molecules introduced
      into an oocyte are able to bind specific endogenous mRNAs and trigger their
      degradation. Subsequent fertilization of these oocytes will result in the
      generation of embryos in which the expression of the gene of interest is
      downregulated, and following the degradation of maternal proteins the role of the
      gene product can be studied. Here, we describe the approach how post
      transcriptional gene silencing can be achieved in oocytes and early embryos using
      siRNA.

PMID- 28456968
TI  - Generating Mouse Models Using Zygote Electroporation of Nucleases (ZEN)
      Technology with High Efficiency and Throughput.
AB  - Mouse models with genetic modifications are widely used in biology and biomedical
      research. Although the application of CRISPR-Cas9 system greatly accelerated the
      process of generating genetically modified mice, the delivery method depending on
      manual injection of the components into the embryos remains a bottleneck, as it
      is laborious, low throughput, and technically demanding. To overcome this
      limitation, we invented and optimized the ZEN (Zygote electroporation of
      nucleases) technology to deliver CRISPR-Cas9 reagents via electroporation. Using
      ZEN, we were able to generate genetically modified mouse models with high
      efficiency and throughput. Here, we describe the protocol in great detail.

PMID- 28456969
TI  - CRISPR/Cas9-Mediated Gene Targeting during Embryogenesis in Swine.
AB  - Ability to disrupt genes is essential in elucidating gene function. Unlike
      rodents or amphibians, it has been difficult to generate gene-targeted embryos in
      large animals. Therefore, studies of early embryo development have been hampered
      in large animals. A recent technology suggests that targeted mutations can be
      successfully introduced during embryogenesis, thus by-passing the need of
      breeding to produce gene-targeted embryos. This is particularly important in
      large animal models because of longer gestation period and higher animal cost.
      Here, we describe a specific approach to disrupt up to two genes simultaneously
      during embryogenesis using the CRISPR/Cas9 technology in swine. The approach can
      help understand the mechanism of zygotic genome activation in large animals.

PMID- 28456970
TI  - Potential Involvement of SCF-Complex in Zygotic Genome Activation During Early
      Bovine Embryo Development.
AB  - Proper timing of degradation of maternal protein reserves is important for early
      embryonic development. The major modification that triggers proteins to
      degradation is ubiquitination, mediated by ubiquitin-proteolytic system. We focus
      here on Skp 1-Cul 1-F-box complex (SCF-complex), E3 ubiquitin-ligase, a part of
      ubiquitin-proteolytic system, which transfer ubiquitin to the substrate protein.
      We describe in this chapter the methods for the characterization of the
      expression profile of mRNA and protein of invariant members of SCF-complex and
      for the definition of SCF-complex activity.

PMID- 28456971
TI  - Use of Histone K-M Mutants for the Analysis of Transcriptional Regulation in
      Mouse Zygotes.
AB  - Histone modifications are dramatically altered during the pronuclear (PN) stage
      of zygotes, and more markedly in paternal than maternal pronuclei. Among various
      types of histone modifications, lysine methylation exhibits the most dynamic
      changes in the PN stage . To analyze the physiological functions of histone
      methylations, it is therefore important to elucidate the mechanism of epigenetic
      reprogramming. However, loss-of-function approaches using mutant histones whose
      lysine residues have been substituted with arginine residues are unable to erase
      histone modifications at all levels, since they are incapable of entirely
      replacing endogenous histones. To solve this problem, we used an alternative
      histone mutant whose lysine residues were substituted with methionine (K-M
      mutants). This mutant cannot be methylated itself but also prevents methylation
      of endogenous histones. We also developed a simple method for analyzing global
      transcription levels in early preimplantation embryos, involving using a
      commercial kit to examine the involvement of histone methylation in zygotic gene
      activation.

PMID- 28456972
TI  - Verification of Decision-Analytic Models for Health Economic Evaluations: An
      Overview.
AB  - Decision-analytic models for cost-effectiveness analysis are developed in a
      variety of software packages where the accuracy of the computer code is seldom
      verified. Although modeling guidelines recommend using state-of-the-art quality
      assurance and control methods for software engineering to verify models, the
      fields of pharmacoeconomics and health technology assessment (HTA) have yet to
      establish and adopt guidance on how to verify health and economic models. The
      objective of this paper is to introduce to our field the variety of methods the
      software engineering field uses to verify that software performs as expected. We
      identify how many of these methods can be incorporated in the development process
      of decision-analytic models in order to reduce errors and increase transparency.
      Given the breadth of methods used in software engineering, we recommend a more in
      depth initiative to be undertaken (e.g., by an ISPOR-SMDM Task Force) to define
      the best practices for model verification in our field and to accelerate
      adoption. Establishing a general guidance for verifying models will benefit the
      pharmacoeconomics and HTA communities by increasing accuracy of computer
      programming, transparency, accessibility, sharing, understandability, and trust
      of models.

PMID- 28456973
TI  - SILAC-Based Comparative Proteomic Analysis of Lysosomes from Mammalian Cells
      Using LC-MS/MS.
AB  - Mass spectrometry-based proteomics of lysosomal proteins has led to significant
      advances in understanding lysosomal function and pathology. The ever-increasing
      sensitivity and resolution of mass spectrometry in combination with labeling
      procedures which allow comparative quantitative proteomics can be applied to shed
      more light on the steadily increasing range of lysosomal functions. In addition,
      investigation of alterations in lysosomal protein composition in the many
      lysosomal storage diseases may yield further insights into the molecular
      pathology of these disorders. Here, we describe a protocol which allows to
      determine quantitative differences in the lysosomal proteome of cells which are
      genetically and/or biochemically different or have been exposed to certain
      stimuli. The method is based on stable isotope labeling of amino acids in cell
      culture (SILAC). Cells are exposed to superparamagnetic iron oxide particles
      which are endocytosed and delivered to lysosomes. After homogenization of cells,
      intact lysosomes are rapidly enriched by passing the cell homogenates over a
      magnetic column. Lysosomes are eluted after withdrawal of the magnetic field and
      subjected to mass spectrometry.

PMID- 28456974
TI  - Quantitative Profiling of Lysosomal Lipidome by Shotgun Lipidomics.
AB  - Recent studies have illuminated novel roles of lysosomes that go far beyond
      simple catabolism and function in the coordination of cellular metabolism and
      signaling. Promising therapeutic strategies emerge from knowledge in the
      molecular mechanisms and physiological roles of lipid metabolism in lysosomes.
      Global monitoring of the function and dysregulation of lysosomal lipid metabolism
      requires a methodology that resolves the complexity of lysosomal lipidome by
      quantitatively detecting hundreds of lipid species of diverse physicochemical
      properties. We describe here a detailed protocol that couples isolation of
      superparamagnetic iron dextran-loaded lysosomes from cultured mammalian cell
      lines with quantitative mass spectrometry-based shotgun lipidomics.

PMID- 28456975
TI  - Analysis of N- and O-Glycosylation of Lysosomal Glycoproteins.
AB  - The vast majority of lysosomal proteins are heavily glycosylated. The present
      protocol describes the method of analyzing N- and O-linked glycans in lysosomal
      proteins of interest. The method is based on using deglycosylating enzymes,
      endoglycosidases, and exoglycosidases. Endoglycosidases catalyze the cleavage of
      an internal bond in an oligosaccharide, while exoglycosidases remove terminal
      carbohydrates from glycans. Different types of carbohydrate residues or chains
      can be removed by specific glycosidases. Removing oligosaccharides with
      glycosidases increases the electrophoretic mobility of a protein. This increase
      in mobility depends on the size and number of removed carbohydrate chains.
      Therefore, the treatment of lysosomal proteins with specific glycosidases
      followed by a western blot analysis of a protein of interest provides a way to
      determine which types of glycans are present in the protein by comparing the gel
      mobility before and after treatment.

PMID- 28456976
TI  - Analyzing Lysosome-Related Organelles by Electron Microscopy.
AB  - Intracellular organelles have a particular morphological signature that can only
      be appreciated by ultrastructural analysis at the electron microscopy level.
      Optical imaging and associated methodologies allow to explore organelle
      localization and their dynamics at the cellular level. Deciphering the biogenesis
      and functions of lysosomes and lysosome-related organelles (LROs) and their
      dysfunctions requires their visualization and detailed characterization at high
      resolution by electron microscopy. Here, we provide detailed protocols for
      studying LROs by transmission electron microscopy. While conventional electron
      microscopy and its recent improvements is the method of choice to investigate
      organelle morphology, immunoelectron microscopy allows to localize organelle
      components and description of their molecular make up qualitatively and
      quantitatively.

PMID- 28456977
TI  - Microscopic Analysis of Lysosomal Membrane Permeabilization.
AB  - Lysosomes and lysosomal proteases have been found to participate during several
      forms of cell death pathways including apoptosis. A critical step in the
      mediation of apoptotic signaling is the release of cathepsins to the cytosol, a
      process known as lysosomal membrane permeabilization (LMP). In this chapter, we
      describe immunofluorescence detection of LMP in cell cultures stained for
      cathepsin B and LAMP-2 using three confocal techniques namely laser scanning,
      spinning disk, and aperture correlation spinning disk confocal to obtain images.
      Image analysis is performed using Huygens software for deconvolution. LMP results
      in a decrease in the fraction of cathepsin B colocalizing with LAMP-2, which is
      quantified through Manders' colocalization coefficient. Analysis of the images
      obtained by the three techniques show the same trend but the magnitude of the
      decrease differs due to the axial resolution. The observations emphasize the use
      of highest possible resolution when determining colocalization.

PMID- 28456978
TI  - Quantitative Co-Localization and Pattern Analysis of Endo-Lysosomal Cargo in
      Subcellular Image Cytometry and Validation on Synthetic Image Sets.
AB  - Late endosomes and lysosomes (LE/LYSs) play a central role in trafficking of
      endocytic cargo, secretion of exosomes, and hydrolysis of ingested proteins and
      lipids. Failure in such processes can lead to lysosomal storage disorders in
      which a particular metabolite accumulates within LE/LYSs. Analysis of endocytic
      trafficking relies heavily on quantitative fluorescence microscopy, but
      evaluation of the huge image data sets is challenging and demands computer
      assisted statistical tools. Here, we describe how to use SpatTrack (
      www.sdu.dk/bmb/spattrack ), an imaging toolbox, which we developed for
      quantification of the distribution and dynamics of endo-lysosomal cargo from
      fluorescence images of living cells. First, we explain how to analyze
      experimental images of endocytic processes in Niemann Pick C2 disease fibroblasts
      using SpatTrack. We demonstrate how to quantify the location of the sterol
      binding protein NPC2 in LE/LYSs relative to cholesterol -rich lysosomal storage
      organelles (LSOs) stained with filipin. Second, we show how to simulate realistic
      vesicle patterns in the cell geometry using Markov Chain Monte Carlo and suitable
      inter-vesicle and cell-vesicle interaction potentials. Finally, we use such
      synthetic vesicle patterns as "ground truth" for validation of two-channel
      analysis tools in SpatTrack, revealing their high reliability. An improved
      version of SpatTrack for microscopy-based quantification of cargo transport
      through the endo-lysosomal system accompanies this protocol.

PMID- 28456979
TI  - Preparation of a Two-Photon Fluorescent Probe for Imaging H2O2 in Lysosomes in
      Living Cells and Tissues.
AB  - Hydrogen peroxide (H2O2) plays important roles in many physiological and
      pathological processes. At the cellular organelle level, the abnormal
      concentrations of H2O2 in the lysosomes may cause redox imbalance and the loss of
      the critical functions of the lysosomes. Herein, we describe the preparation of a
      potent lysosome-targeted two-photon fluorescent probe (Lyso-HP) for the detection
      of H2O2 in the lysosomes in the living cells. This unique fluorescent probe can
      also be employed to effectively detect H2O2 in the living tissues using two
      photon fluorescence microscopy.

PMID- 28456980
TI  - Lysophagy: A Method for Monitoring Lysosomal Rupture Followed by Autophagy
      Dependent Recovery.
AB  - Selective autophagy recognizes specific targets, including damaged mitochondria
      (mitophagy), aggregated proteins (aggrephagy), and invading bacteria (xenophagy)
      to engulf by isolation membrane, and degrades toxic materials within lysosomes.
      We recently revealed that a membrane-damaged lysosome itself also becomes a
      target of autophagy and named this process lysophagy. In this chapter, we
      describe methods for monitoring lysophagy; detecting lysosomal damage by staining
      of galectin and study the subsequent autophagic process in cultured mammalian
      cells.

PMID- 28456981
TI  - Delivery of Cargo to Lysosomes Using GNeosomes.
AB  - Liposomes have been used to improve the intracellular delivery of a variety of
      cargos. Encapsulation of cargos in liposomes leads to improved plasma half-lives
      and minimized degradation. Here, we present a method for improving the selective
      delivery of liposomes to the lysosomes using a guanidinylated neomycin (GNeo)
      transporter. The method for synthesizing GNeo-lipids, incorporating them into
      liposomes, and the enhanced lysosomal delivery of encapsulated cargo are
      presented. GNeo-liposomes, termed GNeosomes, are capable of delivering a
      fluorescent dye to the lysosomes of Chinese hamster ovary cells as shown using
      confocal microscopy. GNeosomes can also be used to deliver therapeutic quantities
      of lysosomal enzymes to fibroblasts isolated from patients with a lysosomal
      storage disorder.

PMID- 28456982
TI  - Lysosomal Acidification in Cultured Astrocytes Using Nanoparticles.
AB  - Following cellular engulfment, nanoparticles end up in the lysosomes, making them
      an ideal tool for modifying the lysosomal environment. Here, we describe how
      acidic nanoparticles can be used to lower the pH of lysosomes in cultured,
      primary astrocytes and thereby increase their degradation capacity. To guarantee
      that the cell culture is completely devoid of professional phagocytes, we
      isolate, expand, and differentiate neural stem cells from embryonic mouse cortex
      to achieve astrocytes for these experiments. Immunostainings with LAMP2-specific
      antibodies can be performed to verify the lysosomal localization of the
      nanoparticles, and the effect on lysosomal acidification can easily be followed
      with LysoTracker dye.

PMID- 28456984
TI  - Detection of Lysosomal Exocytosis in Platelets by Flow Cytometry.
AB  - Flow cytometry is a method that allows high throughput analysis of individual
      cells in suspension. By inclusion of fluorescently labelled antibodies, it is
      possible to analyze the abundance of one or more surface antigens, such as LAMP
      1, without prior lysis of cells. Here we describe the special considerations
      required for the investigation of lysosomal exocytosis from platelets analyzed
      with flow cytometry.

PMID- 28456983
TI  - Analysis of Lysosomal pH by Flow Cytometry Using FITC-Dextran Loaded Cells.
AB  - The acidic environment of the lysosomal lumen provides an optimal milieu for the
      acid hydrolases and is also essential for fusion/fission of endo-lysosomal
      compartments and sorting of cargo. Evidence suggests that maintaining lysosomal
      acidity is essential to avoid disease. In this chapter, we describe a protocol
      for analyzing the lysosomal pH in cultured cells using the fluorescent probe
      fluorescein isothiocyanate (FITC)-dextran together with a dual-emission
      ratiometric technique suitable for flow cytometry. Fluorescence-labeled dextran
      is endocytosed and accumulated in the lysosomal compartment. FITC shows a pH
      dependent variation in fluorescence when analyzed at maximum emission wavelength
      and no variation when analyzing at the isosbestic point, thereby the ratio can be
      used to determine the lysosomal pH. A standard curve is obtained by equilibrating
      intralysosomal pH with extracellular pH using the ionophore nigericin. The
      protocol also includes information regarding procedures to induce lysosomal
      alkalinization and lysosomal membrane permeabilization.

PMID- 28456985
TI  - Detection of Lysosomal Exocytosis by Surface Exposure of Lamp1 Luminal Epitopes.
AB  - Elevation in the cytosolic Ca2+ concentration triggers exocytosis of lysosomes in
      many cell types. This chapter describes a method to detect lysosomal exocytosis
      in mammalian cells, which takes advantage of the presence of an abundant
      glycoprotein, Lamp1, on the membrane of lysosomes. Lamp1 is a transmembrane
      protein with a large, heavily glycosylated region that faces the lumen of
      lysosomes. When lysosomes fuse with the plasma membrane, epitopes present on the
      luminal domain of Lamp1 are exposed on the cell surface. The Lamp1 luminal
      epitopes can then be detected on the surface of live, unfixed cells using highly
      specific monoclonal antibodies and fluorescence microscopy. The main advantage of
      this method is its sensitivity, and the fact that it provides spatial information
      on lysosomal exocytosis at the single cell level.

PMID- 28456986
TI  - Using the MEROPS Database for Investigation of Lysosomal Peptidases, Their
      Inhibitors, and Substrates.
AB  - This chapter describes how to retrieve data on lysosomal peptidases from the
      MEROPS database for proteolytic enzymes, their substrates and inhibitors (
      http://merops.sanger.ac.uk ). Features described in this chapter include the
      summary page, pages for structure, interactions with inhibitors, substrates,
      literature and involvement in physiological pathways, and how to download data
      from the MEROPS FTP site. The lysosomal peptidase legumain is used as an example.

PMID- 28456987
TI  - Next-Generation Sequencing Approaches to Define the Role of the Autophagy
      Lysosomal Pathway in Human Disease: The Example of LysoPlex.
AB  - Next-Generation Sequencing (NGS) technologies have deeply changed the throughput
      of genetic testing allowing analyzing millions of DNA fragments in parallel. One
      key application is the understanding of genetically heterogeneous and complex
      diseases where 50-100 different genes may converge to control the same pathways.
      These disorders cannot be studied using traditional approaches, based on gene-by
      gene Sanger sequencing. We have set up an NGS protocol based on a specific
      selection of DNA regions belonging to about 900 genes of the autophagy-lysosomal
      (ALP) pathway. We here specify all the technical steps and challenges of our
      protocol, named LysoPlex. This is based on the Haloplex technology and together
      with high-coverage sequencing empowers a high and uniform coverage of ALP genes.
      LysoPlex outplays other NGS applications in sensitivity and specificity,
      providing an accurate picture of all variations in ALP genes.

PMID- 28456988
TI  - Gelatin Zymography Using Leupeptin for the Detection of Various Cathepsin L
      Forms.
AB  - Zymography is a highly sensitive method to assess the activities as well as
      molecular weights of enzymes in crude biological fluids and tissue extracts.
      Cathepsin L is a lysosomal cysteine proteinase that is optimally active at
      slightly acidic pH and is highly unstable in alkaline solutions such as electrode
      buffer (pH 8.3). Large amounts of cathepsin L are secreted by various cancer
      cells, where it promotes invasion and metastasis. Leupeptin is a tight-binding
      inhibitor of cysteine proteinases, and its complex with cathepsin L is stable in
      alkaline solutions. Moreover, leupeptin can be easily removed from the complex
      because it is a reversibly binding inhibitor. In addition, leupeptin is too small
      to influence the electrode migration distance of the complex with cathepsin L on
      a sodium dodecyl sulfate-polyacrylamide gel. Here, a novel gelatin zymography
      technique that employs leupeptin to detect pro-, intermediate, and mature
      cathepsin L forms on the basis of their gelatinolytic activities is described.
      Further, the differences in the glycosylation, phosphorylation, and processing
      statuses of lysosomal and secreted cathepsin L forms isolated from cultured HT
      1080 cells are demonstrated using this method.

PMID- 28456989
TI  - Methods for Determination of alpha-Glycosidase, beta-Glycosidase, and alpha
      Galactosidase Activities in Dried Blood Spot Samples.
AB  - The lysosomal storage diseases (LDSs) are a heterogeneous group of inherited
      genetic disorders caused by defects of lysosomal proteins. The accumulation of
      undigested substrates from different catabolic pathways leads to cellular
      dysfunction. LSDs generally presents during early childhood and have a
      devastating impact on the families and on public health. Over the years,
      approaches for treatment of some LSDs have been developed with different
      strategies. Increasing availability of treatments of these diseases has
      accelerated the development of new methods and techniques for rapid diagnosis in
      patients with clinical indication.The use of dried blood spot (DBS) test has been
      proposed as a first tier test to identify patients with Gaucher, Pompe, and Fabry
      diseases. DBS usage is advantageous for the purpose of screening as it is non
      invasive, sensitive, has low-cost and fast turnaround time compared to
      measurements in leucocyte and/or fibroblast culture. This chapter focuses on the
      activity measurement of three lysosomal enzymes (alpha-glucosidase, beta
      glucosidase, and alpha galactosidase) in DBS samples by using fluorescent
      substrates and by the LC-MS/MS (liquid chromatography-mass spectrometry) method.
      All steps of the methods, from preparation of the solutions to calculation of the
      enzyme activity, will be explained in detail.

PMID- 28456990
TI  - Prenatal Diagnosis of Lysosomal Storage Disorders Using Chorionic Villi.
AB  - Prenatal enzymatic diagnosis for an array of lysosomal storage disorders (LSDs)
      can be performed accurately, provided that a confirmed diagnosis by
      biochemical/molecular study in the index case is available and a strict defined
      protocol, specific to each individual disorder is followed. The present chapter
      describes the protocols for reliable and accurate prenatal enzymatic diagnoses by
      fluorometric and spectrophotometric methods of lysosomal storage disorders:
      Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandhoff, GM1,
      Mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy, and Batten
      diseases using uncultured chorionic villi samples. The biological reference
      intervals for enzyme levels in normal and affected fetuses are given for
      interpretation of prenatal results. It is imperative to establish normal
      reference interval in each laboratory to take into account the local environment,
      technical variations, and different ethnicities. Besides, enzyme activity in the
      fetus should be represented as percentage of the mean activity of enzyme of
      normal fetuses. The pitfalls and challenges in prenatal diagnosis as well as
      technical problems in performing enzyme assays are also discussed to help the
      reader in standardization and performing the assays for correct diagnosis.

PMID- 28456991
TI  - Lysosomal Biology in Cancer.
AB  - Cells depend on the lysosome for sequestration and degradation of macromolecules
      in order to maintain metabolic homeostasis. These membrane-enclosed organelles
      can receive intracellular and extracellular cargo through endocytosis,
      phagocytosis, and autophagy. Lysosomes establish acidic environments to activate
      enzymes that are able to break down biomolecules engulfed through these various
      pathways. Recent advances in methods to study the lysosome have allowed the
      discovery of extended roles for the lysosome in various diseases, including
      cancer, making it an attractive and targetable node for therapeutic intervention.
      This review focuses on key aspects of lysosomal biology in the context of cancer
      and how these properties can be exploited for the development of new therapeutic
      strategies. This will provide a contextual framework for how advances in
      methodology could be applied in future translational research.

PMID- 28456992
TI  - Progress and challenges in the treatment of small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is a very aggressive malignancy characterized by
      high cellular proliferation and early metastatic spread. In fact, although SCLC
      is a chemosensitive and radiosensitive disease, the initial responsiveness to
      chemotherapy is usually followed by development of resistance and the prognosis
      remains poor with a median survival of less than 12 months in patients with
      extensive disease (ED-SCLC). Furthermore, no significant progress has been made
      over the last years, with no newly approved drug. For all these reasons, SCLC
      represents for the oncologists a major challenge and an exciting field of
      clinical research. In this review, we analyze the most promising advances in
      development for SCLC with a special focus on antiangiogenic treatments,
      immunotherapy, novel chemotherapeutic and targeted agents.

PMID- 28456993
TI  - Linoleic acid induces migration and invasion through FFAR4- and PI3K-/Akt
      dependent pathway in MDA-MB-231 breast cancer cells.
AB  - An increased risk of developing breast cancer has been associated with high
      levels of dietary fat intake. Linoleic acid (LA) is an essential fatty acid and
      the major omega-6 polyunsaturated fatty acid in occidental diets, which is able
      to induce inappropriate inflammatory responses that contribute to several chronic
      diseases including cancer. In breast cancer cells, LA induces migration. However,
      the signal transduction pathways that mediate migration and whether LA induces
      invasion in MDA-MB-231 breast cancer cells have not been studied in detail. We
      demonstrate here that LA induces Akt2 activation, invasion, an increase in
      NFkappaB-DNA binding activity, miR34a upregulation and miR9 downregulation in MDA
      MB-231 cells. Moreover, Akt2 activation requires EGFR and PI3K activity, whereas
      migration and invasion are dependent on FFAR4, EGFR and PI3K/Akt activity. Our
      findings demonstrate, for the first time, that LA induces migration and invasion
      through an EGFR-/PI3K-/Akt-dependent pathway in MDA-MB-231 breast cancer cells.

PMID- 28456995
TI  - Validation of the 2016 revisions to the WHO classification in lower-risk
      myelodysplastic syndrome.

PMID- 28456994
TI  - Fuelling the mechanisms of asthma: Increased fatty acid oxidation in inflammatory
      immune cells may represent a novel therapeutic target.
AB  - BACKGROUND: Increasing evidence has shown the close link between energy
      metabolism and the differentiation, function, and longevity of immune cells.
      Chronic inflammatory conditions such as parasitic infections and cancer trigger a
      metabolic reprogramming from the preferential use of glucose to the up-regulation
      of fatty acid oxidation (FAO) in myeloid cells, including macrophages and
      granulocytic and monocytic myeloid-derived suppressor cells. Asthma is a chronic
      inflammatory condition where macrophages, eosinophils, and polymorphonuclear
      cells play an important role in its pathophysiology. OBJECTIVE: We tested whether
      FAO might play a role in the development of asthma-like traits and whether the
      inhibition of this metabolic pathway could represent a novel therapeutic
      approach. METHODS: OVA- and house dust mite (HDM)-induced murine asthma models
      were used in this study. RESULTS: Key FAO enzymes were significantly increased in
      the bronchial epithelium and inflammatory immune cells infiltrating the
      respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of
      FAO significantly decreased allergen-induced airway hyperresponsiveness,
      decreased the number of inflammatory cells, and reduced the production of
      cytokines and chemokines associated with asthma. CONCLUSIONS AND CLINICAL
      RELEVANCE: These novel observations suggest that allergic airway inflammation
      increases FAO in inflammatory cells to support the production of cytokines,
      chemokines, and other factors important in the development of asthma. Inhibition
      of FAO by re-purposing existing drugs approved for the treatment of heart disease
      may provide a novel therapeutic approach for the treatment of asthma.

PMID- 28456996
TI  - Tau peptides and tau mutant protein aggregation inhibition by cationic
      polyethyleneimine and polyarginine.
AB  - Tau protein plays a major role in Alzheimer's disease. The tau protein loses its
      functionality by self-aggregation due to the two six-amino acid sequences VQIVYK
      and VQIINK of the protein. Hence it is imperative to find therapeutics that could
      inhibit the self-aggregation of this tau peptide fragments. Here, we study the
      inhibitory potential of a cationic polymer polyethyleneimine (PEI) and a cationic
      polypeptide arginine (Arg) on the aggregation of VQIVYK, and GKVQIINKLDL
      peptides, and tau mutant protein (P301L), found frequently in taupathy. Various
      characterization methods are employed including thioflavin S, transmission
      electron microscopy, and dynamic light scattering to study the
      aggregation/inhibition process in vitro. Results show that PEI and Arg
      significantly inhibit tau peptides and protein aggregation. The study could be
      applied to understand tau protein aggregation mechanism in the presence of
      cationic polymers.

PMID- 28456997
TI  - Pregnancy outcome after a first episode of cerebral vein thrombosis: comment.

PMID- 28456998
TI  - New insights into antidiabetic drugs: Possible applications in cancer treatment.
AB  - Globally at 2014, it was estimated that there was 347 million people with
      diabetes in which 90 percent of them were diagnosed with type 2 diabetes mellitus
      (T2DM). Although the association between diabetes mellitus and cancer risk was
      found about 100 years ago, the issue is not still clear. Many studies especially
      cohort and case-control studies have suggested a higher risk of cancer in
      patients with diabetes mainly in those with type 2 diabetes. Insulin
      concentration is high in these patients, and due to its mitogenic effects, it may
      be a possible hypotheses for higher risk of cancer in diabetic patients.
      Therefore, antidiabetic drugs, which are involved in insulin secretion and
      sensitivity, may have beneficial effects in cancer treatment. Several groups of
      drugs with different mechanisms of action, mostly prescribed orally, are used for
      the treatment of type 2 diabetes mellitus including, insulin sensitizers
      (thiazolidinediones), insulin secretagogues (sulfonylureas), and biguanides. In
      this review, the possible effects of antidiabetic drugs (biguanides,
      thiazolidinediones, and sulfonylureas) and some of their mechanisms for
      overcoming cancer will be discussed.

PMID- 28456999
TI  - Correlation between oral fluid and plasma oxytetracycline concentrations after
      intramuscular administration in pigs.
AB  - The penetration of oxytetracycline (OTC) into the oral fluid and plasma of pigs
      and correlation between oral fluid and plasma were evaluated after a single
      intramuscular (i.m.) dose of 20 mg/kg body weight of long-acting formulation. The
      OTC was detectable both in oral fluid and plasma from 1 hr up to 21 day after
      drug administration. The maximum concentrations (Cmax ) of drug with values of
      4021 +/- 836 ng/ml in oral fluid and 4447 +/- 735 ng/ml in plasma were reached
      (Tmax ) at 2 and 1 hr after drug administration respectively. The area under
      concentration-time curve (AUC), mean residence time (MRT) and the elimination
      half-life (t1/2beta ) were, respectively, 75613 ng * hr/ml, 62.8 hr and 117 hr in
      oral fluid and 115314 ng * hr/ml, 31.4 hr and 59.2 hr in plasma. The OTC
      concentrations were remained higher in plasma for 48 hr. After this time, OTC
      reached greater level in oral fluid. The strong correlation (r = .92) between
      oral fluid and plasma OTC concentrations was observed. Concentrations of OTC were
      within the therapeutic levels for most sensitive micro-organism in pigs (above
      MIC values) for 48 hr after drug administration, both in the plasma and in oral
      fluid.

PMID- 28457000
TI  - Detecting fasciculations in cranial nerve innervated muscles with ultrasound in
      amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Cranial muscle fasciculations may be difficult to detect in
      amyotrophic lateral sclerosis (ALS). Ultrasound (US) detection of fasciculations
      in these muscles may have clinical utility. METHODS: Patients with suspected ALS
      were prospectively enrolled. Nerve conduction studies, needle electromyography
      (EMG), and US examination of cranial muscles were performed. Controls were
      examined by US only. Fasciculations were counted and scored for each muscle after
      10 or 30 seconds. RESULTS: There were 84 patients with ALS. Fasciculations were
      most frequently found in the genioglossus muscle. Overall, detection rates by US
      and EMG were similar, but US was more likely to detect frequent fasciculations.
      Fasciculations were rare in controls, seen in 7 of 1,090 (0.6%) muscles. No
      control had > 5 fasciculations in any muscle. DISCUSSION: Fasciculations were
      frequently detected in cranial muscles of patients with ALS. US was found to be a
      sensitive method, and was not impaired by factors such as anxiety and the
      inability of the patient to relax. Muscle Nerve 56: 1072-1076, 2017.

PMID- 28457001
TI  - Plasma copeptin and metabolic dysfunction in individuals with bipolar disorder.
AB  - AIM: This study aimed to compare plasma copeptin levels, the c-terminal of
      provasopressin, between individuals with bipolar disorder (BD) and healthy
      controls and to assess the relation between copeptin and metabolic parameters.
      METHODS: We measured plasma levels of copeptin in individuals with BD (n = 55)
      and healthy controls (n = 21). Information related to psychiatric/medical
      history, as well as to metabolic comorbidities and laboratorial parameters was
      also captured. Insulin resistance and beta-cell function in basal state were
      calculated from fasting plasma glucose and C-peptide using the HOMA2 calculator.
      Impaired glucose metabolism was defined as pre-diabetes or type 2 diabetes
      mellitus. Copeptin, adiponectin, and leptin plasma levels were determined by
      enzyme-linked immunosorbent assay. RESULTS: Plasma copeptin levels were lower in
      individuals with BD, relative to healthy controls (P < 0.001). There were
      significant interactions between BD and plasma copeptin on beta-cell function
      (rate ratio [RR] = 1.048; P = 0.030) and on leptin levels (RR = 1.087; P =
      0.012), indicating that there was a positive correlation between these markers in
      the BD group, but a negative one in healthy controls. Finally, in individuals
      with BD only, the association between beta-cell function, body mass index (RR =
      1.007; P < 0.001), and insulin resistance (RR = 1.001; P = 0.037) was moderated
      by copeptin levels. CONCLUSION: Copeptin levels were lower in individuals with BD
      than in healthy controls. There were differential associations between copeptin
      and metabolic parameters within the BD and healthy control subgroups, suggesting
      an association between abnormal copeptin and metabolic dysregulation only in the
      BD population.

PMID- 28457002
TI  - Patterns and regulation of silicon accumulation in Synechococcus spp.
AB  - Six clones of the marine cyanobacterium Synechococcus, representing four major
      clades, were all found to contain significant amounts of silicon in culture.
      Growth rate was unaffected by silicic acid, Si(OH)4 , concentration between 1 and
      120 MUM suggesting that Synechococcus lacks an obligate need for silicon (Si).
      Strains contained two major pools of Si: an aqueous soluble and an aqueous
      insoluble pool. Soluble pool sizes correspond to estimated intracellular
      dissolved Si concentrations of 2-24 mM, which would be thermodynamically unstable
      implying the binding of intracellular soluble Si to organic ligands. The Si
      content of all clones was inversely related to growth rate and increased with
      higher [Si(OH)4 ] in the growth medium. Accumulation rates showed a unique
      bilinear response to increasing [Si(OH)4 ] from 1 to 500 MUM with the rate of Si
      acquisition increasing abruptly between 80 and 100 MUM Si(OH)4 . Although these
      linear responses imply some form of diffusion-mediated transport, Si uptake rates
      at low Si (~1 MUM Si) were inhibited by orthophosphate, suggesting a role of
      phosphate transporters in Si acquisition. Theoretical calculations imply that
      observed Si acquisition rates are too rapid to be supported by lipid-solubility
      diffusion of Si through the plasmalemma; however, facilitated diffusion involving
      membrane protein channels may suffice. The data are used to construct a working
      model of the mechanisms governing the Si content and rate of Si acquisition in
      Synechococcus.

PMID- 28457003
TI  - Efficacy and safety of ombitasvir/paritaprevir/ritonavir in dialysis patients
      with genotype 1b chronic hepatitis C.
AB  - AIM: From a pharmacokinetic viewpoint, the use of
      ombitasvir/paritaprevir/ritonavir, one of the standards of care for genotype 1b
      chronic hepatitis C in Japan, could be possible in patients with impaired renal
      function. The aim of this study was to assess the efficacy and safety of this
      combination that have not yet been addressed in patients undergoing dialysis.
      METHODS: A retrospective, multicenter study evaluated the outcome of 12-week
      ombitasvir (non-structural protein [NS]5A inhibitor)/paritaprevir (NS3/4A
      protease inhibitor)/ritonavir combination therapy for dialysis patients. The
      primary end-point was sustained virologic response 12 weeks after therapy
      (SVR12). RESULTS: The subjects were 31 patients with a median age of 64 years
      (range, 49-85 years), including 10 cirrhotic patients. All of the 31 patients had
      an estimated glomerular filtration rate level <15 mL/min/1.73 m2 , defined as end
      stage renal disease (ESRD). Pre-existing resistance-associated substitutions at
      position L31 and Y93 of the NS5A region were detected in 0% and 3.6% (1/28),
      respectively. The rates of rapid virologic response, end-of-treatment response,
      and SVR12 were 93.5% (29/31), 100% (31/31), and 96.8% (30/31), respectively. The
      incidence of adverse events was 35.5% (11/31). Of the 11 patients, one
      discontinued the treatment due to erythema multiforme and thereafter relapsed.
      The most frequent adverse event was pruritus (6.5%; 2/31). CONCLUSIONS: The
      present study suggests that ombitasvir/paritaprevir/ritonavir combination therapy
      is effective and safe for genotype 1b chronic hepatitis C patients undergoing
      dialysis due to ESRD.

PMID- 28457004
TI  - Colonization strategy of the endophytic plant growth-promoting strains of
      Pseudomonas fluorescens and Klebsiella oxytoca on the seeds, seedlings and roots
      of the epiphytic orchid, Dendrobium nobile Lindl.
AB  - AIMS: Orchids form strong mycorrhizal associations, but their interactions with
      bacteria are poorly understood. We aimed to investigate the distribution of plant
      growth promoting rhizobacteria (PGPR) at different stages of orchid development
      and to study if there is any selective specificity in choosing PGPR partners.
      METHODS AND RESULTS: Colonization patterns of gfp-tagged Pseudomonas fluorescens
      and Klebsiella oxytoca were studied on roots, seeds, and seedlings of Dendrobium
      nobile. Endophytic rhizobacteria rapidly colonized velamen and core parenchyma
      entering through exodermis and the passage cells, whereas at the early stages,
      they stayed restricted to the surface and the outer layers of the protocorms and
      rhizoids. The highest amounts of auxin (indole-3-acetic acid) were produced by K.
      oxytoca and P. fluorescens in the nitrogen-limiting and NO3 -containing media
      respectively. Bacterization of D. nobile seeds resulted in promotion of their in
      vitro germination. The plant showed no selective specificity to the tested
      strains. Klebsiella oxytoca demonstrated more intense colonization activity and
      more efficient growth promoting impact under tryptophan supplementation, while P.
      fluorescens revealed its growth-promoting capacity without tryptophan.
      CONCLUSIONS: Both strategies are regarded as complementary, improving adaptive
      potentials of the orchid when different microbial populations colonize the plant.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study enlarges our knowledge on orchid
      microbial interactions, and provides new features on application of the nonorchid
      PGPR in orchid seed germination and conservation.

PMID- 28457005
TI  - Letter to the editor.

PMID- 28457006
TI  - Quantitative electromyography in ambulatory boys with Duchenne muscular
      dystrophy.
AB  - INTRODUCTION: This study's objective was to evaluate quantitative
      electromyography (QEMG) using multiple-motor-unit (multi-MUP) analysis in
      Duchenne muscular dystrophy (DMD). METHODS: Ambulatory DMD boys, aged 5-15 years,
      were evaluated with QEMG at 6-month intervals over 14 months. EMG was performed
      in the right biceps brachii (BB) and tibialis anterior (TA) muscles. Normative
      QEMG data were obtained from age-matched healthy boys. Wilcoxon signed-rank tests
      were performed. RESULTS: Eighteen DMD subjects were enrolled, with a median age
      of 7 (interquartile range 7-10) years. Six-month evaluations were performed on 14
      subjects. QEMG showed significantly abnormal mean MUP duration in BB and TA
      muscles, with no significant change over 6 months. CONCLUSIONS: QEMG is a
      sensitive electrophysiological marker of myopathy in DMD. Preliminary data do not
      reflect a significant change in MUP parameters over a 6-month interval; long-term
      follow-up QEMG studies are needed to understand its role as a biomarker for
      disease progression. Muscle Nerve 56: 1361-1364, 2017.

PMID- 28457007
TI  - Altered axonal excitability properties in facial palsy.
AB  - INTRODUCTION: Axonal excitability measures give insight into the biophysical
      properties of peripheral nerve axons. In this study we applied these techniques
      to the study of facial palsy. METHODS: Thirty patients with established facial
      palsy due to unresolved Bell's palsy or herpes zoster (>6 months duration), tumor
      invasion of the facial nerve, or traumatic facial nerve injury were assessed
      using facial nerve excitability techniques. RESULTS: Full recordings were
      obtained in 23 patients (15 unrecovered Bell's palsy or herpes zoster, 5 trauma,
      3 tumor-related). Compared with normal controls, the facial palsy group
      demonstrated changes in stimulus response properties, threshold electrotonus,
      refractoriness, superexcitability, and I/V slope. Depolarizing threshold
      electrotonus distinguished between viral and non-viral etiologies on subgroup
      analysis. DISCUSSION: In this cross-sectional study, established facial palsy
      demonstrated findings similar to those seen in studies of regenerated axons. The
      improved understanding of underlying axonal characteristics offered by the
      technique may guide future treatment. Muscle Nerve 57: 268-272, 2018.

PMID- 28457008
TI  - A life-threatening ruxolitinib discontinuation syndrome.

PMID- 28457009
TI  - Comparison of direct sampling and brochoalveolar lavage for determining active
      drug concentrations in the pulmonary epithelial lining fluid of calves injected
      with enrofloxacin or tilmicosin.
AB  - Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial
      fluid (PELF) was measured and compared to plasma drug concentrations in eight
      healthy calves. Enrofloxacin (Baytril(r) 100) was administered at a dose of 12.5
      mg/kg subcutaneously (SC), and tilmicosin (Micotil(r) 300) was administered at a
      dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar
      lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each
      calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin
      by HPLC. Pharmacokinetic analysis was performed on the concentrations in each
      fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by
      AUC in DS samples was 137 +/- 72% higher than in plasma, but in BAL samples, this
      value was 535 +/- 403% (p < .05). The concentrations of tilmicosin in DS and BAL
      samples exceeded plasma drug concentrations by 567 +/- 189% and 776 +/- 1138%,
      respectively. The enrofloxacin/ciprofloxacin concentrations collected by DS were
      significantly different than those collected by BAL, but the tilmicosin
      concentrations were not significantly different between the two methods.
      Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine
      respiratory disease pathogens but tilmicosin did not reach MIC levels for these
      pathogens in any fluids.

PMID- 28457010
TI  - Evaluation of cardiovascular effects of intravenous robenacoxib in dogs.
AB  - The objective of the study was to assess the cardiovascular effects of
      intravenous (IV) dosing with robenacoxib (Onsior(r) ) in conscious adult healthy
      beagle dogs. The study employed a randomized, open, placebo-controlled, four
      phase Latin square design. A total of eight dogs received a single dose of 2
      mg/kg and 4 mg/kg IV robenacoxib (test groups), 2 mg/kg subcutaneous (SC)
      robenacoxib (reference dose and route), and IV isotonic saline (control). There
      were no significant differences between groups for clinical observations, buccal
      mucosal bleeding time or blood hematology, coagulation, and clinical chemistry
      variables in all eight dogs. In a subset of four dogs, no significant differences
      between groups were detected using telemetric assessment for arterial blood
      pressure, heart rate, electrocardiogram, or body temperature over 8 hr postdose.
      In conclusion, no significant cardiovascular effects were detected after a single
      IV dose of 2 or 4 mg/kg robenacoxib in conscious healthy dogs.

PMID- 28457011
TI  - Diagnosis of inherited platelet disorders on a blood smear: a tool to facilitate
      worldwide diagnosis of platelet disorders.
AB  - : Essentials There are many hereditary platelet disorders (HPD) but diagnosing
      these is challenging. We provide a method to diagnose several HPDs using standard
      blood smears requiring < 100 uL blood. By this approach, the underlying cause of
      HPD was characterized in ~25-30% of referred individuals. The method facilitates
      diagnosis of HPD for patients of all ages around the world. SUMMARY: Background
      Many hereditary thrombocytopenias and/or platelet function disorders have been
      identified, but diagnosis of these conditions remains challenging. Diagnostic
      laboratory techniques are available only in a few specialized centers and, using
      fresh blood, often require the patient to travel long distances. For the same
      reasons, patients living in developing countries usually have limited access to
      diagnosis. Further, the required amount of blood is often prohibitive for
      pediatric patients. Objectives By a collaborative international approach of four
      centers, we aimed to overcome these limitations by developing a method using
      blood smears prepared from less than 100 MUL blood, for a systematic diagnostic
      approach to characterize the platelet phenotype. Methods We applied
      immunofluorescence labelling (performed centrally) to standard air-dried
      peripheral blood smears (prepared locally, shipped by regular mail), using
      antibodies specific for proteins known to be affected in specific hereditary
      platelet disorders. Results By immunofluorescence labelling of blood smears we
      characterized the underlying cause in 877/3217 (27%) patients with suspected
      hereditary platelet disorders (HPD). Currently about 50 genetic causes for HPD
      are identified. Among those, the blood smear method was especially helpful to
      identify MYH9 disorders/MYH9-related disease, biallelic Bernard-Soulier syndrome,
      Glanzmann thrombasthenia and gray platelet syndrome. Diagnosis could be
      established for GATA1 macrothrombocytopenia, GFI1B macrothrombocytopenia, beta1
      tubulin macrothrombocytopenia, filamin A-related thrombocytopenia and Wiskott
      Aldrich syndrome. Conclusion Combining basic and widely available preanalytical
      methods with the immunomorphological techniques presented here, allows detailed
      characterization of the platelet phenotype. This supports genetic testing and
      facilitates diagnosis of hereditary platelet disorders for patients of all ages
      around the world.

PMID- 28457012
TI  - Body composition in men with anorexia nervosa: Longitudinal study.
AB  - OBJECTIVE: To compare body composition patterns before and after complete weight
      restoration in men with anorexia nervosa. METHOD: Dual-energy X-ray
      absorptiometry (DXA) was used to measure body composition patterns in 10 men with
      anorexia nervosa before and after complete weight restoration, and in 10 healthy
      men matched to age and patients' post-treatment body mass index (BMI). RESULTS:
      Before weight restoration, men with anorexia nervosa displayed lower total body
      fat mass (FM) and lean mass (LBM) than those in the healthy comparison group,
      with a greater FM loss from the extremity than the trunk region. After short-term
      weight restoration, patients displayed complete normalization in total LBM and
      FM, but greater deposition of FM in the trunk region. CONCLUSION: Short-term
      weight restoration can normalize body composition patterns in men with anorexia
      nervosa, but results in a central adiposity phenotype. The clinical implication
      of this finding is unknown, but should be explored given the high levels of
      concern about central adiposity in anorexia nervosa.

PMID- 28457013
TI  - e-Health-based management of patients receiving oral anticoagulation therapy:
      results from the observational thrombEVAL study.
AB  - : Essentials e-Health based health care by an expert centre may advance
      management of oral anticoagulation. Outcome of patients was compared between an e
      health based coagulation service and regular care. Patients in the coagulation
      service cohort experienced a significantly better clinical outcome. Lower risk
      for adverse events was related to anticoagulation-specific and non-specific
      outcome. SUMMARY: Background Management of oral anticoagulation (OAC) therapy is
      essential to minimize adverse events in patients receiving vitamin K-antagonists
      (VKAs). Data on the effect of e-health-based anticoagulation management systems
      on the clinical outcome of OAC patients are limited. Objectives To compare the
      clinical outcome of OAC patients managed by an e-health-based coagulation service
      (CS) with that of patients receiving regular medical care (RMC). Methods The
      prospective multicenter cohort study thrombEVAL (NCT01809015) comprised 1558
      individuals receiving RMC and 760 individuals managed by a CS. Independent study
      monitoring and adjudication of endpoints by an independent review panel were
      implemented. Results The primary study endpoint (composite of thromboembolism,
      clinically relevant bleeding and death) occurred in 15.7 per 100 patient-years
      (py) with RMC and in 7.0 per 100 py with the CS (rate ratio [RR], 2.3; 95%
      confidence interval [CI], 1.7-3.1). Rates for major and clinically relevant
      bleeding were higher with RMC than with the CS: 6.8 vs. 2.6 and 10.1 vs. 3.6 per
      100 py, respectively. Thromboembolic events showed an RR of 1.5 (95% CI, 0.8-2.6)
      comparing RMC with the CS. Hospitalization (RR, 2.6; 95% CI, 2.3-3.0) and all
      cause mortality (RR, 4.6; 95% CI, 2.8-7.7) were markedly more frequent with RMC.
      In Cox regression analysis with adjustment for age, sex, cardiovascular risk
      factors, comorbidities, treatment characteristics and sociodemographic status,
      hazard ratios (HR) for the primary endpoint (HR, 2.2; 95% CI, 1.5-3.4),
      clinically relevant bleeding (HR, 3.1; 95% CI, 1.7-5.5), hospitalization (HR,
      2.2; 95% CI, 1.8-2.8) and all-cause mortality (HR, 5.6; 95% CI, 2.9-11.0) favored
      CS treatment. Conclusions In this study, e-health-based management of OAC therapy
      was associated with a lower frequency of OAC-specific and non-specific adverse
      events.

PMID- 28457015
TI  - Pregnancy outcome after a first episode of cerebral vein thrombosis: reply.

PMID- 28457014
TI  - Unusual dimerization of a BcCsp mutant leads to reduced conformational dynamics.
AB  - : Cold shock proteins (Csp) constitute a family of ubiquitous small proteins that
      act as RNA-chaperones to avoid cold-induced termination of translation. All
      members contain two subdomains composed of 2 and 3 beta-strands, respectively,
      which are connected by a hinge loop and fold into a beta-barrel. Bacillus
      caldolyticus Csp (BcCsp) is one of the most studied members of the family in
      terms of its folding, function, and structure. This protein has been described as
      a monomer in solution, although a recent crystal structure showed dimerization
      via domain swapping (DS). In contrast, other cold shock proteins of the same fold
      are known to dimerize in a nonswapped arrangement. Hypothesizing that reducing
      the size of the hinge loop may promote swapping as in several other DS proteins
      with different folds we deleted two residues from these region (BcCsp?36-37),
      leading to a protein in monomer-dimer equilibrium with similar folding stability
      to that of the wild-type. Strikingly, the crystal structure of BcCsp?36-37
      revealed a nonswapped dimer with its interface located at the nucleic acid
      binding surface, showing that the deletion led to structural consequences far
      from the perturbation site. Concomitantly, circular dichroism experiments on
      BcCsp?36-37 demonstrated that binding of the oligonucleotide hexathymidine
      disrupts the dimer. Additionally, HDXMS shows a protective effect on the protein
      structure upon dimerization, where the resulting interactions between ligand
      binding surfaces in the dimer reduced the extent of exchange throughout the whole
      protein. Our work provides evidence of the complex interplay between
      conformational dynamics, deletions, and oligomerization within the Csp protein
      family. DATABASES: Structural data are available in the Protein Data Bank under
      accession number 5JX4.

PMID- 28457016
TI  - Patterns of primary care utilization before and after living kidney donation.
AB  - BACKGROUND: Annual visits with a primary care provider (PCP) are recommended for
      living kidney donors to monitor long-term health postdonation, yet adherence to
      this recommendation is unknown. METHODS: We surveyed 1170 living donors from our
      center from 1970 to 2012 to ascertain frequency of PCP visits pre- and
      postdonation. Interviews occurred median (IQR) 6.6 (3.8-11.0) years post
      transplant. We used multivariate logistic regression to examine associations
      between donor characteristics and PCP visit frequency. RESULTS: Overall, only
      18.6% had less-than-annual PCP follow-up postdonation. The strongest predictor of
      postdonation PCP visit frequency was predonation PCP visit frequency. Donors who
      had less-than-annual PCP visits before donation were substantially more likely to
      report less-than-annual PCP visits postdonation (OR=9.8 14.421.0, P<.001). Men
      were more likely to report less-than-annual PCP visits postdonation (adjusted
      OR=1.2 1.62.3, P<.01); this association was amplified in unmarried/noncohabiting
      men (aOR=2.4 3.96.3, P<.001). Donors without college education were also more
      likely to report less-than-annual PCP visits postdonation (aOR=1.3 1.82.5 ,
      P=.001). CONCLUSIONS: The importance of annual PCP visits should be emphasized to
      all living donors, especially those with less education, men (particularly single
      men), and donors who did not see their PCP annually before donation.

PMID- 28457017
TI  - Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of
      vascular inflammation in human endothelial cells.
AB  - SCOPE: The physiological relevance of contemporary cell culture studies is often
      perplexing, given the use of unmetabolized phytochemicals at supraphysiological
      concentrations. We investigated the activity of physiologically relevant
      anthocyanin metabolite signatures, derived from a previous pharmacokinetics study
      of 500 mg 13 C5 -cyanidin-3-glucoside in eight healthy participants, on soluble
      vascular adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) in human
      endothelial cells. METHODS AND RESULTS: Signatures of peak metabolites
      (previously identified at 1, 6, and 24 h post-bolus) were reproduced using pure
      standards and effects were investigated across concentrations ten-fold lower and
      higher than observed mean (<5 MUM) serum levels. Tumor necrosis factor-alpha (TNF
      alpha)-stimulated VCAM-1 was reduced in response to all treatments, with maximal
      effects observed for the 6 and 24 h profiles. Profiles tested at ten-fold below
      mean serum concentrations (0.19-0.44 MUM) remained active. IL-6 was reduced in
      response to 1, 6, and 24 h profiles, with maximal effects observed for 6 h and 24
      h profiles at concentrations above 2 MUM. Protein responses were reflected by
      reductions in VCAM-1 and IL-6 mRNA, however there was no effect on phosphorylated
      NFkappaB-p65 expression. CONCLUSION: Signatures of anthocyanin metabolites
      following dietary consumption reduce VCAM-1 and IL-6 production, providing
      evidence of physiologically relevant biological activity.

PMID- 28457018
TI  - Modulation of the N400 component in relation to hypomanic personality traits in a
      word meaning ambiguity resolution task.
AB  - AIM: High levels of hypomanic personality traits have been associated with an
      increased risk of developing bipolar disorder (BD). Changes in semantic content,
      impaired verbal associations, abnormal prosody, and abnormal speed of language
      are core features of BD, and are thought to be related to semantic processing
      abnormalities. In the present study, we used event-related potentials to
      investigate the relation between semantic processing (N400 component) and
      hypomanic personality traits. METHODS: We assessed 65 healthy young adults on the
      Hypomanic Personality Scale (HPS). Event-related potentials were recorded during
      a semantic ambiguity resolution task exploring semantic ambiguity (polysemous
      word ending a sentence) and congruency (target word semantically related to the
      sentence). RESULTS: As expected, semantic ambiguity and congruency both elicited
      an N400 effect across our sample. Correlation analyses showed a significant
      positive relationship between the Social Vitality subscore of the HPS and N400
      modulation in the frontal region of interest in the incongruent unambiguous
      condition, and in the frontocentral region of interest in the incongruent
      ambiguous condition. CONCLUSION: We found differences in semantic processing
      (i.e., detection of incongruence and semantic inhibition) in individuals with
      higher Social Vitality subscores. In the light of the literature, we discuss the
      notion that a semantic processing impairment could be a potential marker of
      vulnerability to BD, and one that needs to be explored further in this clinical
      population.

PMID- 28457019
TI  - Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso
      occlusive crisis and steady state.
AB  - : Essentials The role of von Willebrand Factor (VWF) in the pathophysiology of
      sickle cell disease is unclear. We assessed markers of VWF during admission for
      vaso-occlusive crisis (VOC) and steady state. VWF reactivity was higher during
      VOC and was associated with inflammation and neutrophil activation. Hyper
      adhesive VWF may promote VOC in sickle cell disease. SUMMARY: Background
      Endothelial activation plays a central role in the pathophysiology of vaso
      occlusion in sickle cell disease (SCD), facilitating adhesive interactions with
      circulating blood cells. Upon activation, various adhesive molecules are
      expressed, including von Willebrand factor (VWF). Increased VWF levels have been
      observed in patients with SCD during steady state. However, the role of VWF in
      the pathogenesis of SCD vaso-occlusion is unclear. Objectives To longitudinally
      assess the quantity and reactivity of VWF and its regulating protease ADAMTS-13
      during vaso-occlusive crisis (VOC). Methods In this observational study, we
      obtained sequential blood samples in adult SCD patients during VOC. Results VWF
      reactivity was significantly higher during VOC (active VWF, VWF glycoprotein Ib
      binding activity, and high molecular weight multimers), whereas platelet count
      and levels of ADAMTS-13 antigen and ADAMTS-13 activity were concomitantly lower
      than during steady state. Levels of VWF antigen, VWF propeptide (VWF:pp) and
      ADAMTS-13 specific activity did not change during VOC. VWF reactivity correlated
      strongly with markers of inflammation and neutrophil activation, and was
      inversely correlated with the platelet count. In patients who developed acute
      chest syndrome, levels of VWF, VWF:pp and active, hyperadhesive VWF were
      significantly higher, whereas ADAMTS-13 activity was lower, than in patients
      without this complication. Conclusions We provide the first evidence that VOC in
      SCD is associated with increased reactivity of VWF, without a pronounced ADAMTS
      13 deficiency. This hyper-reactivity may be explained by resistance of VWF to
      proteolysis, secondary to processes such as inflammation and oxidative stress.
      Hyperadhesive VWF, scavenging blood cells in the microcirculation, may thereby
      amplify and sustain VOC in SCD.

PMID- 28457020
TI  - Virus-host interplay in hepatitis B virus infection and epigenetic treatment
      strategies.
AB  - Worldwide, chronic hepatitis B virus (HBV) infection is a major health problem
      and no cure exists. Importantly, hepatocyte intrusion by HBV particles results in
      a complex deregulation of both viral and host cellular genetic and epigenetic
      processes. Among the attempts to develop novel therapeutic approaches against HBV
      infection, several options targeting the epigenomic regulation of HBV replication
      are gaining attention. These include the experimental treatment with 'epidrugs'.
      Moreover, as a targeted approach, the principle of 'epigenetic editing' recently
      is being exploited to control viral replication. Silencing of HBV by specific
      rewriting of epigenetic marks might diminish viral replication, viremia, and
      infectivity, eventually controlling the disease and its complications.
      Additionally, epigenetic editing can be used as an experimental tool to increase
      our limited understanding regarding the role of epigenetic modifications in viral
      infections. Aiming for permanent epigenetic reprogramming of the viral genome
      without unspecific side effects, this breakthrough may pave the roads for an
      ambitious technological pursuit: to start designing a curative approach utilizing
      manipulative molecular therapies for viral infections in vivo.

PMID- 28457021
TI  - Clinical Effects of a Pharmacist Intervention in Acute Wards - A Randomized
      Controlled Trial.
AB  - The purpose of the study was to investigate the clinical effect of a clinical
      pharmacist (CP) intervention upon admission to hospital on inpatient harm and to
      assess a potential educational bias. Over 16 months, 593 adult patients taking
      >=4 medications daily were included from three Danish acute medicine wards.
      Patients were randomized to either the CP intervention or the usual care
      (prospective control). To assess a potential educational bias, a retrospective
      control group was formed by randomization. The CP intervention comprised
      medication history, medication reconciliation, medication review and entry of
      proposed prescriptions into the electronic prescribing system. The primary
      outcome of inpatient harm was identified using triggers from the Institute of
      Healthcare Improvement Global Trigger Tool. Harms were validated and rated for
      severity by two independent and blinded outcome panels. Secondary end-points were
      harms per patient, length of hospital stay, readmissions and 1-year mortality.
      Harm affected 11% of the patients in the intervention group compared to 17% in
      the combined control group, odds ratio (OR) 0.57 (CI 0.32-1.02, p = 0.06). The
      incidence of harm was similar in the intervention and prospective control groups,
      OR 0.80 (CI 0.40-1.59, p = 0.52) but occurred less frequently in the intervention
      than in the retrospective control group OR 0.46 (CI 0.25-0.85, p = 0.01). An
      educational bias from the intervention to the control group might have
      contributed to this negative outcome. In conclusion, the CP intervention at
      admission to hospital had no statistically significant effect on inpatient harm.

PMID- 28457022
TI  - Quercetin protects against atherosclerosis by inhibiting dendritic cell
      activation.
AB  - SCOPE: Quercetin is a typical flavonol with atheroprotective effects, but the
      effect of quercetin on dendritic cell (DC) maturation in relation to
      atherosclerosis has not yet been clearly defined. Thus, we investigated whether
      quercetin can inhibit DC maturation and evaluated its potential value in
      atherosclerosis progression in ApoE-/- mice. METHODS AND RESULTS: Quercetin
      consumption inhibited DC activation, inflammatory response and suppressed the
      progression of atherosclerosis in ApoE-/- mice. Subsequently, quercetin treatment
      inhibited the phenotypic and functional maturation of DCs, as evidenced not only
      by downregulation of CD80, CD86, MHC-II, IL-6 and IL-12 but also by a reduction
      in the ability to stimulate T cell allogeneic proliferation. Finally, an in vitro
      study demonstrated that quercetin inhibited DC maturation via upregulation of
      Dabs, which then downregulated the Src/PI3K/Akt-NF-kappaB-inflammatory pathways.
      CONCLUSIONS: Our data indicate that quercetin attenuates atherosclerosis
      progression by regulating DC activation via Dab2 protein expression.

PMID- 28457023
TI  - The effect of population-based mammography screening in Dutch municipalities on
      breast cancer mortality: 20 years of follow-up.
AB  - Long-term follow-up data on the effects of screening are scarce, and debate
      exists on the relative contribution of screening versus treatment to breast
      cancer mortality reduction. Our aim was therefore to assess the long-term effect
      of screening by age and time of implementation. We obtained data on 69,630 breast
      cancer deaths between 1980 and 2010 by municipality (N = 431) and age of death
      (40-79) in the Netherlands. Breast cancer mortality trends were analyzed by
      defining the municipality-specific calendar year of introduction of screening as
      Year 0. Additionally, log-linear Poisson regression was used to estimate the
      turning point in the trend after Year 0, per municipality, and the annual
      percentage change (APC) before and after this point. Twenty years after
      introduction of screening breast cancer mortality was reduced by 30% in women
      aged 55-74 and by 34% in women aged 75-79, compared to Year 0. A similar and
      significant decrease was present in municipalities that started early (1987-1992)
      and late (1995-1997) with screening, despite the difference in availability of
      effective adjuvant treatment. In the age groups 55-74 and 75-79, the turning
      point in the trend in breast cancer mortality was estimated in Years 2 and 6
      after the introduction of screening, respectively, after which mortality
      decreased significantly by 1.9% and 2.6% annually. These findings show that the
      implementation of mammography screening in Dutch municipalities is associated
      with a significant decline in breast cancer mortality in women aged 55-79,
      irrespective of time of implementation.

PMID- 28457024
TI  - Conserved nucleolar stress at the onset of cell death.
AB  - Cell death pervasiveness among multicellular eukaryotes suggested that some core
      steps of cell death may be conserved. This could be addressed by comparing the
      course of cell death in organisms belonging to distinct eukaryotic kingdoms. A
      search for early cell death events in a protist revealed nucleolar
      disorganization similar to the nucleolar stress often reported in dying animal
      cells. This indicated a conserved role for the nucleolus at the onset of
      eukaryotic cell death and leads one to consider the course of cell death as a
      succession of unequally conserved modules.

PMID- 28457025
TI  - Decisional conflict between treatment options among end-stage renal disease
      patients evaluated for kidney transplantation.
AB  - Although kidney transplantation provides a significant benefit over dialysis,
      many patients with end-stage renal disease (ESRD) are conflicted about their
      decision to undergo kidney transplant. We aimed to identify the prevalence and
      characteristics associated with decisional conflict between treatment options in
      ESRD patients presenting for transplant evaluation. Among a cross-sectional
      sample of patients with ESRD (n=464) surveyed in 2014 and 2015, we assessed
      decisional conflict through a validated 10-item questionnaire. Decisional
      conflict was dichotomized into no decisional conflict (score=0) and any
      decisional conflict (score>0). We investigated potential characteristics of
      patients with decisional conflict using bivariate and multivariable logistic
      regression. The overall mean age was 50.6 years, with 62% male patients and 48%
      African American patients. Nearly half (48.5%) of patients had decisional
      conflict regarding treatment options. Characteristics significantly associated
      with decisional conflict in multivariable analysis included male sex, lower
      educational attainment, and less transplant knowledge. Understanding
      characteristics associated with decisional conflict in patients with ESRD could
      help identify patients who may benefit from targeted interventions to help
      patients make informed, value-based, and supported decisions when deciding how to
      best treat their kidney disease.

PMID- 28457026
TI  - Antimicrobial Resistance in ICU : An Avalanche in Waiting !

PMID- 28457027
TI  - Changing Antimicrobial Resistance Pattern of Isolates from an ICU Over a 3 Year
      period.
AB  - OBJECTIVE: To study the changing patterns of antimicrobial resistance in gram
      negative bacilli esp. Escherichia coli, Klebsiella pneumoniae, Pseudomonas
      aeruginosa species and Gram positive Staphylococcus aureus isolates from a 37
      bedded ICU of a private hospital. METHODS: Antibiotic susceptibilities were
      determined by using disk diffusion and Vitek-2 system. RESULTS: A total of 13410
      clinical samples were screened over a period of 3 years, among which 16.77
      percent (2250 isolates) were culture positive. In recent years there has been an
      increased incidence of extended-spectrum beta- lactamase (ESBL). The ESBL
      producing Escherichia coli and Klebsiella pneumonia has shown an increase in
      resistance to the tune of 80-90% from 2011 to 2013. The prevalence of resistant
      strains of Acinetobacter species and Pseudomonas aeruginosa has shown an increase
      in Imipenem and Meropenem resistance at the rate of 75-80%. CONCLUSIONS:
      Antibiotic resistance has shown an increase in gram negative pathogens and
      thereby has created a significant problem in choosing the right antibiotic for
      empirical usage. Rise in resistance has left little choice for the clinicians to
      select antibiotics. Klebsiella pneumonia ESBL and Escherichia coli ESBL have
      become dominant organisms in the ICU. Piperacillin + Tazobactum, Imipenem and
      Amikacin have decreased sensitivity against Enterobacter. A number of old
      antibiotic compounds such as Polymyxins, Fosfomycin, and Aminoglycosides are re
      emerging as valuable alternatives for the treatment of ESBL producing bacteria.
      Cases of MDR Escherichia coli and Klebsiella pneumonia bacteria have increased in
      recent years and are now the most frequent cause of hospital acquired infections.

PMID- 28457028
TI  - Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2
      Diabetes in India.
AB  - INSTRUCTION: Insulin is the oldest of the currently available treatment options
      in Type 2 diabetes mellitus (T2DM) and is considered as the most effective
      glucose lowering agent. Despite this, decision on starting insulin therapy is
      often delayed in India as well as worldwide due to various barriers at both
      patient and physician levels. Appropriate insulin dosing and titration is also
      critical to the successful achievement of tight glycaemic control. OBJECTIVE: To
      provide simple and easily implementable guidelines to primary care physicians on
      appropriate insulin dosing and titration of various insulin regimens for both
      initiation and intensification. METHODOLOGY: Each insulin regimen (once daily
      [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal
      bolus) was presented and evaluated for dosing and titration based on established
      guidelines, data from approved pack inserts, and published scientific literature.
      These evaluations were then factored into the national context based on the
      expert committee representatives patient-physician experience in their clinical
      practice and common therapeutic practices followed in India. RESULTS:
      Recommendations for dosing and titration of basal, basal-plus, premixed and basal
      bolus insulins were developed. The key recommendations are that insulin doses can
      be adjusted once or twice weekly; adjustment can be based on lowest/mean of three
      recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG)
      values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL
      and the dose should be reduced by 10-20% for patients reporting
      hypoglycaemia(<70mg/dL). CONCLUSIONS: The consensus based recommendations
      mentioned in this paper will be a useful reference tool for health care
      practitioners, to initiate, optimise and intensify insulin therapy and to
      successfully achieve optimal glucose control.

PMID- 28457029
TI  - Role of ACE and IL-1beta Gene Polymorphisms in Erythropoeitin Hyporesponsive
      Patients with Chronic Kidney Disease with Anemia.
AB  - BACKGROUND: Hyporesponse to erythropoietin is a common problem seen in around 5
      10% of patients. Recently the focus from these remediable factors has been
      shifted to the non-modifiable innate factors i.e polymorphism of ACE and IL-1B
      gene and studies have shown that DD genotype and IL-1B CC genotype have lower
      erythropoietin requirement. The aim of our study was to evaluate the role of ACE
      and IL-1B gene polymorphisms in erythropoietin hyporesponse in CKD patients with
      anemia. METHODS: A total of 50 patients were selected. After taking pre-informed
      written consent, they were segregated into two groups, group A and B with 25
      patients in each group. Group A included CKD stage III-IV patients and Group B
      included CKD stage V patients who were on regular maintenance. All patients were
      given erythroepoietin and response was monitored using erythropoietin resistance
      index (ERI). Genotyping of ACE and IL-1B genes were done and serum levels of ACE
      and IL-1B were measured. Mean values of ERI were compared between different
      genotype subgroups and analysed using binary regression analysis. RESULTS: The
      study group included 6 patients with diabetic nephropathy and out of these
      4(66.6%) had DD genotype. On comparing the effect of ACE polymorphism on ERI
      levels it was seen that the mean ERI values in DD subgroup were significantly
      lower (16.97+/-5.35, 21.88+/-6.25, 22.69+/-8.35 at 1,3 and 5th month) as compared
      to ID (18.16+/-3.39, 24.17+/-3.66, 32.74+/-9.95 and II (20.73+/-5.17, 27.74+/
      7.30, 41.08+/-13.83 U/Kg/g/dL). In the case of IL-1B the mean ERI values were
      lowest in the TT subgroup (16.46+/-4.45, 21.96+/-5.77,23.98+/-8.48) as compared
      to CC (19.49 +/-5.62,25.46+/-7.07, 33.59+/-12.61) and CT (18.12+/-4.27,24.14+/
      5.70, 31.89+/-13.83 U/Kg/g/dL). The mean serum values of ACE were in a decreasing
      trend i.e DD> ID> II (238.05 +/- 52.46, 194.73+/-50.28 and 162.99+/-39.71 ng/ml,
      (p < 0.05). The mean serum values of IL1B in CC, CT and TT were 23.24+/-28.77,
      18.32+/-16.25, 23.34+/-13.83 pg/ml (p>0.05). CONCLUSIONS: D allele positively
      affected the serum ACE level but there was no association between IL-1B genotype
      and its levels. ACE gene polymorphism has an important role in determining the
      response to EPO and progression of CKD. Pre-treatment screening for genotype may
      help in predicting the patients at risk and poor responders.

PMID- 28457030
TI  - Evaluation of Effect of Vitamin D Deficiency on Anemia and Erythropoietin
      Hyporesponsiveness in Patients of Chronic Kidney Disease.
AB  - BACKGROUND: The role of vitamin D deficiency and inflammation levels in renal
      anemia has been documented. However, no study is available in India where the
      role of vitamin D supplementation in patients with hyporesponsiveness to
      increased doses of erythropoietin is available. Hence this study. MATERIAL AND
      METHODS: This study was conducted on 50 adult patients of CKD, on regular, twice
      weekly hemodialysis. It included 38 cases in group A with deficient serum vitamin
      D levels (<30 ng/ml) and 12 cases in group B with sufficient vitamin D levels
      (>30 ng/ml). Both groups of cases were receiving erythropoietin in a dose of 4000
      I.U. subcutaneously twice weekly following dialysis and had failed to show rise
      in hemoglobin (Hb) >1gm/dl after one month, hence erythropoietin was increased to
      6000 I.U. Group A was given additional vitamin D in a dose of 60000 I.U. orally,
      once a week for next three months along with erythropoietin 6000 I.U. where as
      Group B served as control. Hematological and renal parameters, ESR, high
      sensitivity C reactive protein (HsCRP) and serum ferritin were estimated at
      baseline and then at one monthly intervals for next four months. Parathyroid
      hormone (iPTH), serum B12, folic acid and vitamin D (25OHD3) were measured at the
      start and end of the study only. Erythropoietin resistance index (ERI) was
      calculated to evaluate dose response. RESULTS: Basal ERI, HsCRP and ESR and serum
      ferritin were raised in both the groups. At the end of four months, there was a
      significant increase in the Hb and hematocrit (Hct) (p<.001) and a significant
      fall in ERI, ESR, HsCRP, serum ferritin and iPTH (p<.001) in group A. Group B,
      also had a significant increase in the hemoglobin and hematocrit (p<.001) and
      decrease in ERI, ESR, HsCRP, serum ferritin and iPTH which was not significant.
      Basal vitamin D and ERI had a positive and insignificant correlation (r=0.05;
      p=0.756) in group A where as a negative and insignificant correlation was
      observed between them at the end of four months (r= -0.195; p >0.05).
      CONCLUSIONS: vitamin D play an important role in reducing inflammation and
      thereby in the cure of anemia in EPO hyporesponsive CKD patients and needs to be
      supplemented, if deficiency is found.

PMID- 28457031
TI  - Prepubertal Childhood Onset Type 2 Diabetes Mellitus: Four Case Reports.
AB  - BACKGROUND: The prevalence of childhood onset type 2 diabetes (T2D) is
      increasing, but prepubertal T2D is still unusual. METHODS: We report four cases
      of T2D with onset at or below 10 years of age registered at a tertiary diabetes
      centre in southern India.T2D was diagnosed based on the absence of ketosis, good
      beta cell reserve as shown by the C peptide assay, absence of GAD antibodies and
      pancreatic calculi, and response to oral hypoglycemic agents. RESULTS: All four
      patients were female, obese and had acanthosis nigricans. Polycystic ovarian
      syndrome and fatty liver were found in two cases. All were treated with metformin
      but two patients needed insulin additionally. Two had hypercholesterolemia and
      hypertension. One patient developed non-proliferative diabetic retinopathy on
      follow up. CONCLUSIONS: T2D is now beginning to be seen in the first decade of
      life. A proper clinical work up of children with diabetes will prevent
      misclassification as type 1 diabetes and help avoid unnecessary insulin therapy.

PMID- 28457032
TI  - Prevalence of Cardiovascular Risk Factors among Diabetic Population and Awareness
      of Diabetes among Diabetic Patients: A Population Based Himalayan Study.
AB  - BACKGROUND: To determine the prevalence of modifiable cardiovascular risk factors
      among adults with diabetes in the remote Himalayan areas, at elevation range from
      350 meters (1,148ft) to 6900 meters (22,966ft) above sea level, in the Indian
      state of Himachal Pradesh. MATERIAL AND METHODS: Study was conducted in 21 rural
      areas of Himachal Pradesh situated at 2200 to 10,000 feet altitude. Non-pregnant
      diabetic adults (>18years) were surveyed, through 32 diabetic camps. The date and
      place of the camp was decided one month in advance and advertised. Detailed
      history including smoking status, weight, height, waist circumference, body mass
      index recorded. Fasting or random blood glucose, glycated hemoglobin, lipid
      profile measured and blood pressure recorded. RESULTS: Total 909 eligible adult
      diabetics were surveyed (59.73% male) with a mean duration of disease 38.14+/
      4.56 months.35.54% adults were smoker and 67.55% were either overweight or obese
      54.04% males and 77.53% females had waist circumference above Indian standards.
      78.35% had A1C >7% and 61.50% had blood pressure measurements above target
      (>140/80mmhg). 56.74% had elevated LDL and only 6.32% had all blood glucose,
      blood pressure and cholesterol at recommended levels. CONCLUSIONS: High
      prevalence of modifiable cardiovascular risk factors in addition to uncontrolled
      blood glucose is widespread, placing diabetics at higher risk for cardiovascular
      disease. Improved disease management system in addition to public awareness
      campaign is needed for people with diabetes in this region of the country.

PMID- 28457033
TI  - Clinical and Biochemical Characteristics of Exertional Heat Stroke among
      Paratroopers in Agra, India.
AB  - OBJECTIVE: The purpose of this study was to assess the clinical profile,
      biochemical parameters and outcome in a series of 78 patients of heat stroke
      admitted and treated in a military hospital in India. METHODS: This was a
      prospective study in a military hospital. A total of 78 patients of exertional
      heat stroke admitted and treated over more than 2 years are reported. Cooling
      measures started immediately on site of occurrence, carried on during evacuation
      and in hospital, IV normal saline initiated, clinical symptoms and signs were
      noted. Blood was collected and sent for hematological, biochemical and
      coagulation parameters. RESULTS: Clinical features noted were violent behavior(
      20.51%), confusional state (58.97%),coma (29.48%), seizure (33.33%),and vomiting
      (26.92%).Vital parameters were recorded and laboratory parameters revealed
      hypophosphatemia, hyponatremia, hypokalemia along with raised transaminases,
      creatinine kinase and lactic dehydrogenase. Patients were managed with cooling
      measures, IV fluids and supportive measures. All of them survived to be
      discharged in a mean of 8.34 days. CONCLUSIONS: Timely diagnosis, prompt
      intervention in form of effective cooling measures to reduce the temperature to
      acceptable levels within 30 mins, volume resuscitation, judicious use of
      ionotropes after adequate volume replacement and effective supportive care
      resulted in a favourable outcome.

PMID- 28457034
TI  - Autoimmune Encephalitis: An update.

PMID- 28457035
TI  - Statistical Considerations for Randomized Controlled Trials [RCTs] -
      Understanding Superiority, Equivalence and Non-inferiority Designs.

PMID- 28457036
TI  - Understanding Forensic Pharmacology: What Indian Physicians Need to Know?

PMID- 28457037
TI  - Empyema Thoracis Presenting as Abdominal Mass.

PMID- 28457038
TI  - Magnetic Resonance Imaging Features of Neuroglycopenia.

PMID- 28457039
TI  - Carcinoma of Unknown Primary Presenting as Peripheral Symmetric Gangrene.
AB  - Cancer of unknown primary accounts for almost 4-5% of all invasive cancers and
      consists of tumors from various primary sources with considerable heterogeneity
      in biology and behaviour. Most of these tumors present with symptoms due to
      distant metastasis. Histology, immunohistochemistry and molecular profiling is
      the mainstay for diagnosis. In most cases of adenocarinoma associated with
      paraneoplastic acral vascular syndrome (PAVS), a site in the lung, ovary or
      uterus is discernible. Here we report a case of metastatic adenoarcinoma of
      unknown primary presenting as PAVS, a case which to the best of our knowledge has
      not been reported in published literature.

PMID- 28457040
TI  - Tolosa-Hunt Syndrome and Ocular Myasthenia: A Rare Coexistence or Real
      Association.
AB  - Tolosa- Hunt syndrome is a rare steroid responsive disorder caused by granulation
      tissue involving the cavernous sinus or superior orbital fissure presenting as
      painful ophthalmoplegia and facial pain. In this report, we describe coexistence
      of Tolosa-Hunt syndrome with ocular myasthenia which may point towards an
      autoimmune etiological basis behind the cavernous sinus granulation tissue
      formation and also offered therapeutic challenge to ameliorate the symptoms.

PMID- 28457041
TI  - Sternocleidomastoid Abscess Mimicking a Thyroid Swelling in a Young Female.
AB  - Primary pyomyositis is a bacterial infection of skeletal muscle with acute or
      subacute clinical course. This usually present with localized abscess.We report a
      case of an 18 years old female presenting with swelling in midline of neck moving
      with deglutition mimicking a thyroid swelling. On further investigation patient
      was confirmed to have sternocleidomastoid myositis. Previous case reports have
      showed various etiologies for development of abscess. After thorough examination
      and investigations, patient was found to have an idiopathic sternocleidomastoid
      abscess which responded well to empirical antibiotic therapy.This is a very
      uncommon condition and very sparsely reported and so far, to the best of our
      knowledge there is no case report from India.

PMID- 28457042
TI  - Bilateral Anterior Opercular Syndrome.
AB  - Opercular syndrome, also known as Foix-Chavany-Marie syndrome, is characterised
      by paralysis of the facial, masticatory, pharyngeal, laryngeal, brachial and
      tongue muscles. It is a cortical form of pseudobulbar palsyo which is commonly
      caused by a vascular aetiology. The clinical presentation is anarthria, weakness
      of voluntary muscles involving face, tongue, pharynx, larynx, and masticatory
      muscles. However, autonomic reflexes and emotional functions of these structures
      are preserved. We report a case of a 61 year old man who had difficulty in
      chewing, swallowing and vocalising since one and a half month, which on imaging
      was found to be opercular syndrome.

PMID- 28457043
TI  - Mycobacterium Tuberculosis Infection at Pacemaker Implantation Site.
AB  - Expanding clinical indications of cardiac rhythm management have led to an
      increased use of pacemaker implantation which is associated with increased
      incidence of pacemaker infections. Staphylococcus aureus and epidermidis account
      for the majority of pacemaker infections. Infection of implantable cardiac
      devices by mycobacterium species, particularly mycobacterial tuberculosis is
      rare. We present a case of delayed pacemaker pocket infection with tuberculosis
      and review of literature of pacemaker infections with mycobacterium species.

PMID- 28457044
TI  - Paraneoplastic Dermatomyositis.
AB  - Dermatomyositis and its association with malignancy is well known. Though many
      tumors like breast, ovary, lung carcinomas are reported to be associated with it,
      cervical carcinoma is a very rare one. Tumors in these patients are usually
      unmasked by abnormal findings in the medical history and physical examination.
      Here we report case of a postmenopausal female who presented with subacute onset
      of weakness of all four limbs. Treatment of the underlying tumor relieved the
      symptoms of dermatomyositis in our patient.

PMID- 28457045
TI  - Carcinoma Prostate Presenting as Multiple Cranial Nerve Palsy.
AB  - Metastatic prostatic carcinoma commonly involves bones and extra pelvic lymph
      nodes. CNS involvement is unusual and particularly the occurence of
      leptomeningeal metastasis is extremely rare, with few cases described in the
      literature.1 The reported incidence at autopsy vary from 0.6 to 4.4 percent.2 We
      report a 65 year old male who presented with multiple cranial nerve palsies due
      to leptomeningeal metastasis in carcinoma prostate treated with orchidectomy and
      planned for radiotherapy and antiandrogen therapy.

PMID- 28457046
TI  - Gastrointestinal Histoplasmosis and CMV Co-Infection in an Immunocompetent Host.
AB  - A middle aged male with no known comorbidities presented with history of colicky
      abdominal pain, low grade fever and weight loss. Laboratory parameters were
      normal except low albumin. Imaging showed multiple areas of mural thickening with
      enhancement in jejunum & ileum. On Colonoscopy there was a thickened and deformed
      ileum with multiple ulcers. The biopsy showed co-infection of CMV and
      histoplasma, urine antigen for histoplasma was positive and CMV DNA detected in
      blood. He was successfully treated with combination of Valgancyclovir and
      Amphotericin-B followed by itraconazole.

PMID- 28457047
TI  - Plummer-Vinson Syndrome with Simultaneous Mid-esophageal Growth.
AB  - Patterson Brown Kelly or Plummer-Vinson syndrome is characterized by dysphagia,
      iron deficiency anemia and post-cricoidal esophageal web. Waldenstorm introduced
      the term 'sideropenic dysphagia' because of absence of stainable iron in the bone
      marrow. There is increased incidence of upper aero-digestive tract carcinoma in
      patients with Plummer-Vinson syndrome has been well established. The reported
      rates range from 4% to 16%, with almost all cases occurring at the postcricoid
      location.We have reported here a case of a 48-year-old woman with dysphagia ,
      upper esophageal web and iron deficiency anemia . Dilatation of esophageal web
      with subsequent endoscopy showed mid- esophageal growth which on biopsy showed
      squamous cell carcinoma.

PMID- 28457048
TI  - Asymptomatic Presentation of Large Cardiac Hydatid.
AB  - Hydatid cyst is a tissue parasitic infection caused by tapeworm Echinococcus
      granulosus. Common location for hydatid cysts are the liver (65%) and the lungs
      (25%). Cardiac hydatid cyst is seen rarely, occurring in about 0.5-2% of all
      cases of hydatid disease. We present this case of 45 years female who presented
      with short duration of dry cough and atypical chest pain. Chest X ray showed
      cardiomegaly with round bulge at the right heart border and curvilinear
      calcification in left upper abdomen in the region of spleen. Transthoracic
      echocardiography (TTE) depicted cystic lesion in Right Ventricle free wall
      causing compression of right atrial and ventricular cavity. Cardiac CT confirmed
      this cyst as hydatid cyst. Patient underwent successful excision of right
      ventricular hydatid cyst.

PMID- 28457049
TI  - Calcium and Calcium Salts.

PMID- 28457050
TI  - Gerty Cori and Carbohydrate Metabolism.

PMID- 28457051
TI  - Prevalence of HIV/Tb Co-infection among HIV Patients: Hospital Based Study from
      Northern Part of India.

PMID- 28457052
TI  - Utilization of Colistin in a Tertiary Care Hospital: A Prospective Observational
      Study.

PMID- 28457053
TI  - Clinical Evidence for Utilizing Cannabinoids in the Elderly.

PMID- 28457054
TI  - Efficacy of Medical Cannabis for Treatment of Refractory Epilepsy in Children and
      Adolescents with Emphasis on the Israeli Experience.

PMID- 28457055
TI  - Short-Term Efficacy of CBD-Enriched Hemp Oil in Girls with Dysautonomic Syndrome
      after Human Papillomavirus Vaccination.
AB  - BACKGROUND: Cannabidiol (CBD)-based treatments for several diseases, including
      Tourette's syndrome, multiple sclerosis, epilepsy, movement disorders and
      glaucoma, are proving to be beneficial and the scientific clinical background of
      the drug is continuously evolving. OBJECTIVES: To investigate the short-term
      effect of CBD-enriched hemp oil for relieving symptoms and improving the life
      quality (QOL) in young girls with adverse drug effects (ADRs) following human
      papillomavirus (HPV) vaccine. METHODS: In this anecdotal, retrospective,
      "compassionate-use", observational, open-label study, 12 females (age 12-24
      years) with severe somatoform and dysautonomic syndrome following HPV vaccination
      were given sublingual CBD-rich hemp oil drops, 25 mg/kg per day supplemented by 2
      5 mg/ml CBD once a week until a maximum dose of 150 mg/ml CBD per day was reached
      over a 3 month period. Patients' quality of life was evaluated using the medical
      outcome short-form health survey questionnaire (SF-36). RESULTS: Two patients
      dropped out due to iatrogenic adverse events and another two patients stopped the
      treatment early due to lack of any improvement. SF-36 showed significant benefits
      in the physical component score (P < 0.02), vitality (P < 0.03) and social role
      functioning (P < 0.02) after the treatment. The administration of hemp oil also
      significantly reduced body pain according to the SF-36 assessment. No significant
      differences from the start of treatment to several months post-treatment were
      detected in role limitations due to emotional reactions (P = 0.02). CONCLUSIONS:
      This study demonstrated the safety and tolerability of CBD-rich hemp oil and the
      primary efficacy endpoint. Randomized controlled trials are warranted to
      characterize the safety profile and efficacy of this compound.

PMID- 28457056
TI  - Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular
      Indications.
AB  - BACKGROUND: A flowering plant of variegated ingredients and psychoactive
      qualities, cannabis has long been used for medicinal and recreational purposes.
      Currently, cannabis is approved in several countries for indications of
      symptomatic alleviation. However, limited knowledge on the benefits and risks
      precludes inclusion of cannabis in standard treatment guidelines. This review
      provides a summary of the available literature on the use of cannabis and
      cannabinoid-based medicines in palliative oncology. Favorable outcomes are
      demonstrated for chemotherapy-induced nausea and vomiting and cancer-related
      pain, with evidence of advantageous neurological interactions. Benefit in the
      treatment of anorexia, insomnia and anxiety is also suggested. Short- and long
      term side effects appear to be manageable and to subside after discontinuation of
      the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical
      studies in a wide range of cancer cells and some animal models. Further research
      is needed before cannabis can become a part of evidence-based oncology practice.

PMID- 28457057
TI  - The Role of Cannabinoids in the Treatment of Cancer in Pediatric Patients.

PMID- 28457058
TI  - Cannabis in Inflammatory Bowel Diseases: from Anecdotal Use to Medicalization?

PMID- 28457059
TI  - Cannabidiol as a Therapy for ASIA Syndrome? An Editorial on a Novel Study.

PMID- 28457060
TI  - Complications of Post-Burn Tissue Expansion Reconstruction: 9 Years Experience
      with 42 Pediatric and 26 Adult Patients.
AB  - BACKGROUND: Burn scar reconstruction is extremely challenging, even for the most
      proficient reconstructive surgeon. Within the arsenal of tools at the plastic
      surgeon's disposal, tissue expansion provides an efficient modality for
      reconstruction despite the reported complication rates. OBJECTIVES: To critically
      review our experience with tissue expansion for burn scar reconstruction,
      comparing particularly the adult and pediatric populations. METHODS: We conducted
      a retrospective study of the outcomes of patients who underwent burn scar
      reconstruction with tissue expansion at Hadassah Medical Center between January
      2003 and July 2012. The data included patient age, anatomical site of expansion,
      number of procedures, and associated complications. The outcomes of the above
      mentioned populations were also compared with those in a control group of
      patients undergoing reconstruction with tissue expansion for indications other
      than burn scars. RESULTS: Sixty-seven tissue expansion procedures were carried
      out in 50 patients, 42 in the pediatric population (< 16 years of age) and 25 in
      the adult population. Complications were observed in 10 of the 42 pediatric
      procedures (23.8%) and in 3 of the 25 adult procedures (12%). This difference was
      found to be statistically significant. When the complication rate for each
      population was compared to its control group (tissue expansion for indications
      other than burn scar reconstruction, such as reconstruction for motor vehicle
      accident scarring, congenital nevi, or vascular malformations), no statistically
      significant difference was found between them (complication rates 19.8% and
      12.5%, respectively). Furthermore, there was no statistically significant
      difference in complication rates between the different anatomical areas of
      expansion within both populations undergoing burn scar reconstruction. Most of
      the complicated cases completed successful reconstruction. CONCLUSIONS: Tissue
      expansion is a useful surgical tool in post-burn scar reconstruction, both in the
      adult and pediatric populations and in all anatomic sites, despite consistently
      high complication rates, especially in the pediatric population. This
      complication rate is not higher than in patients undergoing tissue expansion for
      indications other than burn scar reconstruction.

PMID- 28457061
TI  - Association between Fatty Liver Disease and Hyperplastic Colonic Polyp.
AB  - BACKGROUND: Hyperplastic polyps (HPs) of the colon are the most common colorectal
      polyps. Metabolic syndrome components such as obesity and hyperlipidemia are
      considered the most common etiological factors for HPs as well contributing to
      the pathogenesis of fatty liver disease. OBJECTIVES: To determine the possible
      association between biopsy-proven steatohepatitis and hyperplastic colonic
      polyps. METHODS: This retrospective cohort observational study conducted at the
      Holy Family Hospital in Nazareth, Israel, included subjects who underwent
      screening colonoscopy over a 2 year period. Data were extracted from the patient
      charts and included demographics, anthropometric measurements, vital signs,
      underlying diseases, medical therapy, laboratory data, and results of the liver
      biopsy. The colonoscopy report and pathological report of each extracted polyp
      were also evaluated. RESULTS: A total of 223 patients were included in the study:
      123 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) and 100
      patients without NASH who served as the control. Fourteen colonic adenomas (11%
      of patients) were found in the NASH group vs. 16 (16%) in the control group (P =
      0.9); 28 HPs were found in the NASH group (22.7%) vs. 8 in the control group (8%)
      (P < 0.05). The multivariate analysis, after adjusting for, age, C-reactive
      protein and smoking, showed that the presence of NASH (OR 1.69, 95%CI 1.36-1.98,
      P < 0.01) was associated with increased risk for HP. CONCLUSIONS: Our study found
      an association between biopsy-proven steatohepatitis and the burden of
      hyperplastic polyp.

PMID- 28457062
TI  - Profile of Patients Presenting for Cataract Surgery in a Public Hospital: A 15
      Year Perspective.
AB  - BACKGROUND: In recent decades cataract surgery has shifted slowly from public
      hospitals to ambulatory surgery centers, demonstrating changes in the profile of
      patients presenting to public hospitals for cataract surgery. These changes may
      potentially affect the complexity of surgeries, their volume, resident training,
      and perhaps also visual outcomes and patient satisfaction. OBJECTIVES: To assess
      the changes in the medical and demographic characteristics of patients undergoing
      cataract surgery in a public hospital over a period of 15 years. METHODS: We
      retrospectively reviewed the records of patients undergoing preoperative
      assessment before cataract surgery. Records for the period October 2000 to
      January 2001 (100 patients), October 2006 to January 2007 (100 patients), and
      October 2013 to January 2014 (150 patients) were assessed for demographic,
      systemic and ocular related parameters. RESULTS: There was a significant increase
      in the average age of patients (70.4, 72.4, 73.9 years, P = 0.026), with a
      significant increase in the percentage of patients of Arab ethnicity (17%, 11%,
      28.7%, P = 0.002), and concomitant systemic co-morbidities (38%, 46%, 64.7%, P <
      0.0001). There was an increase in the percentage of patients with narrow
      palpebral fissures (0%, 2%, 8%, P = 0.003), deep-set eyes (2%, 4%, 18%, P <
      0.0001), dense nuclear sclerotic cataract (38%, 34.4%, 56.9%, P = 0.001), and a
      significant increase in the percentage of patients taking alpha-blocking
      medications (0%, 8%, 10.7 %, P = 0.004). CONCLUSIONS: Patients presenting for
      cataract surgery in 2013 compared to those in earlier periods are older, sicker
      and have more ocular conditions potentially affecting cataract surgery outcomes,
      patient satisfaction and residents' training.

PMID- 28457063
TI  - Prognostic Factors in Differentiated Thyroid Cancer Revisited.
AB  - BACKGROUND: More than 90% of all thyroid cancers are differentiated thyroid
      carcinomas (DTC) with a 10 year survival rate greater than 90%. The commonly used
      risk stratification systems for DTC include: European Organization for Research
      and Treatment of Cancer (EORTC), AGES (Age, histologic Grade, Extent of tumor,
      Size), AMES (Metastasis) and MACIS (Completeness of resection, local Invasion).
      Other systems are also utilized. Several new factors that may be involved in DTC
      risk stratification have emerged in recent studies, with other "traditional"
      factors being challenged. OBJECTIVES: To present recent updates in the literature
      on new potential prognostic factors for DTC. METHODS: We conducted a literature
      review and analysis of publications regarding DTC prognostic factors or risk
      stratification published in the last 10 years. RESULTS: Several new factors with
      potential prognostic implications for DTC were noted, including family history,
      lymph node involvement parameters, positive PET-CT findings, multifocal disease,
      thyroglobulin level and several molecular markers including BRAF. Increasing age
      is associated with poorer outcome in DTC; however, recent studies suggest that
      the cutoff point of 45 years may be contested. Furthermore, several studies have
      shown contradictory results regarding male gender as a negative prognostic
      factor, thus questioning its prognostic significance. CONCLUSIONS: A number of
      new factors with potential prognostic implications for DTC have emerged and
      should be addressed. However, their role and possible inclusion in new staging
      systems has yet to be determined.

PMID- 28457064
TI  - Tissue Expansion: Still Not Expendable.

PMID- 28457065
TI  - Transoral Robotic Appraoch for Resection of a Giant Hypopharyngeal Fibroma.

PMID- 28457066
TI  - Hyena Attack of a Child's Head and Face: Plastic Reconstructive Surgery
      Challenge.

PMID- 28457067
TI  - Rapidly Progressing Fatal Neurobrucellosis in a Healthy Child in an Endemic Area
      in Southern Israel.

PMID- 28457068
TI  - Acquired Hemophilia A in a Patient with Non-Small Cell Lung Carcinoma: A Rare
      Paraneoplastic Phenomenon.

PMID- 28457069
TI  - Lingua Villosa Nigra.

PMID- 28457070
TI  - The Link between Diabetes and Cardiovascular Disease: The Epidemiological
      Perspective.

PMID- 28457071
TI  - Border Treatment of both Body and Soul.

PMID- 28457072
TI  - The Dedicated Enough Doctor: The Limits of Medical Altruism in the 21st Century.
AB  - BACKGROUND: The unique characteristics of the next generation of medical
      professionals in Israel and the current model of physician employment in the
      country may pose a real threat to the high quality of both public clinical care
      and medical education in the near future, and to the continued flourishing of
      clinical research. According to the Israel Medical Association's general
      obligations for Israeli physicians, the doctor should place the patient's
      interests foremost in his or her mind, before any other issue. This has led many
      to believe that selflessness or altruism should be among a physician's core
      values. Is the application and realization of these obligations compatible with
      the realities of 21st century medicine? Is altruism still a legitimate part of
      the modern medical world? The Y generation, those born in the 1980s and 1990s,
      now comprise the majority of the population of residents and young specialists.
      They have been characterized as ambitious, self-focused, entrepreneurial, lacking
      loyalty to their employer, and seeking immediate gratification. Under these
      circumstances, is it possible to encourage or even teach altruism in medical
      school? Demands on physicians' time are increasing. The shortage of doctors, the
      growth of the population, the way in which health care is consumed, and the
      increasing administrative burden have all gnawed away at the time available for
      individual patient care. This time needs to be protected. The altruism of
      physicians could become the guarantee of first-rate care in the public sector.
      The continued existence of clinical research and high level clinical teaching
      also depends on the allocation of protected time. In light of the emerging
      generation gap and the expected dominance of Y generation physicians in the
      medical workforce in the near future, for whom altruism may not be such an
      obvious value, solutions to these predicaments are discussed.

PMID- 28457073
TI  - Association between Enlarged Axillary Lymph Nodes and Silicone Breast Implant
      Ruptures seen on Magnetic Resonance Imaging.
AB  - BACKGROUND: Silicone breast augmentation is a common cosmetic surgery. Previous
      case reports demonstrated lymphadenopathy in the presence of implant ruptures.
      OBJECTIVES: To investigate the association between enlarged axillary lymph nodes
      and silicone implant ruptures as seen on breast magnetic resonance imaging (MRI).
      METHODS: Two groups were derived retrospectively from breast MRI reports in our
      institution for the period December 2011-May 2014. A search of our hospital
      records for "silicone" and "lymph node" was performed (group A), and the
      relationship between the presence of enlarged nodes and ruptures was evaluated.
      The prevalence of ruptures in the presence of nodes was calculated and the
      association between MRI imaging features and ruptures evaluated. A search for
      "silicone" and "implant rupture" was performed (group B) and, as for group A, the
      relationship between the presence of ruptures and nodes was evaluated and the
      prevalence of enlarged nodes in the presence of ruptures calculated. RESULTS:
      Group A comprised 45 women with enlarged nodes. Intracapsular ruptures were
      associated with nodes (P = 0.005), while extracapsular ruptures showed a trend of
      association with nodes (P = 0.08). The prevalence of ruptures in the presence of
      nodes was 31.4%. Nodes associated with ruptures showed a strong silicone signal
      (P = 0.008) and absent enhancement (P = 0.005). Group B comprised 73 women with
      ruptures. Enlarged nodes were associated with both intra- and extracapsular
      ruptures (P < 0.001 and P = 0.002 respectively). The prevalence of nodes in the
      presence of ruptures was 22.2%. CONCLUSIONS: Enlarged axillary nodes were
      associated with ruptures in two groups of patients. This finding can guide
      clinical decisions when either enlarged nodes or ruptures are encountered in
      patients with silicone implants. The association between silicone lymphadenopathy
      and implant rupture raises concerns regarding the role of rupture in silicone
      induced systemic disease.

PMID- 28457074
TI  - Nephrolithiasis in Israel: Epidemiological Characteristics of Return Patients in
      a Tertiary Care Center.
AB  - BACKGROUND: The prevalence and etiology of nephrolithiasis vary, depending on
      geography, gender and ethnicity. OBJECTIVES: To analyze the demographic data of
      return nephrolithiasis patients in a tertiary care center. METHODS: We
      retrospectively reviewed our prospective registry database of return patients
      seen at our outpatient clinic for nephrolithiasis. Data included gender, age at
      first visit, age at first stone event, body mass index (BMI), self-reported
      hypertension, diabetes mellitus (DM), and hyperlipidemia. All patients were seen
      at least twice and had undergone a metabolic workup. RESULTS: A total of 260
      return patients were seen during the period 2010-2015. The male:female ratio was
      3.1:1. Mean age at the first stone event was 44.1 years. Median time elapsed
      since the first stone event to medical evaluation was 5 years (interquartile
      range 1-12 years). Hypertension was reported by 33.1% of the patients, DM by
      23.5% and hyperlipidemia by 30.4%. All three diseases were reported by 11.5% of
      patients. The metabolic abnormalities detected were hypocitraturia (60%), low
      urine volume (LUV) (60%), hypercalciuria (40.8%), hyperoxaluria (24.2%),
      hyperuricosuria (16.5%) and hyperuricemia (13.5%). Stone compositions from most
      to least frequent were calcium-oxalate (81%), calcium-phosphate (11.9%) and uric
      acid (7.1%). We also found that 24.6% were obese (BMI >= 30 kg/m2) and showed
      higher rates of hypertension, DM, hyperlipidemia, hyperuricemia and
      hyperuricosuria compared with non-obese patients. Significantly higher rates of
      obesity and LUV were detected in females compared with males. Patients over age
      45 had lower rates of hyperuricemia compared with patients >= 45 years old (P =
      0.038). CONCLUSIONS: Factors related to nephrolithiasis can potentially differ
      among populations and countries. Our findings emphasize the significance of
      individualized national health programs to address local issues.

PMID- 28457075
TI  - Comparative Characteristics of the 2009 Pandemic Influenza A (H1N1) Virus and
      2010-2011 Seasonal Influenza in Pediatric Patients.
AB  - BACKGROUND: In March 2009 the pandemic influenza A (H1N1) strain was identified.
      The disease initially appeared to be accompanied by complications and high
      mortality rates. It became an endemic virus during the influenza season in our
      region, along with the classical seasonal H3N2. OBJECTIVES: To identify the
      burden of pandemic influenza, its effect in pediatric patients, and complicated
      hospitalizations, compared to seasonal influenza years after the pandemic.
      METHODS: A retrospective observational study was conducted at a tertiary
      hospital. Data were collected from the medical records of all children who were
      hospitalized from April 2009 to 2011 with laboratory-confirmed influenza.
      RESULTS: Of 191 patients with influenza, 100 had the 2009 pandemic influenza, 62
      had seasonal influenza, and 29 had H1N1 in 2010-2011. Patients with the 2009 H1N1
      were characterized by older age, more co-morbidity conditions and more symptoms
      including fever, cough and rhinitis on admission. No significant differences in
      outcomes between the groups were recorded. Of patients hospitalized with pandemic
      influenza in 2009, 28% had complicated hospitalizations, compared with 17.7% of
      patients hospitalized with seasonal influenza in 2010-11. Children with pandemic
      influenza received more oseltamivir (Tamiflu(r)) (94% vs. 19.4%, P < 0.001) and
      more antibiotics than the other groups. CONCLUSIONS: The type of influenza had no
      effect on outcome. There were no significant differences between groups in the
      percentages of in-hospital mortality, admission to intensive care units,
      prolonged hospitalization (> 9 days), or the development of complications during
      hospitalization.

PMID- 28457076
TI  - Improvement in Creatinine Clearance after Open Heart Surgery in Infants as an
      Early Indicator of Surgical Success.
AB  - BACKGROUND: Early surgical correction of congenital heart malformations in
      neonates and small infants may be complicated by acute kidney injury (AKI), which
      is associated with higher morbidity and mortality rates, especially in patients
      who require dialysis. Glomerular filtration rate (GFR) is considered the best
      measurement of renal function which, in neonates and infants, is highly dependent
      on heart function. OBJECTIVES: To determine whether measurements of creatinine
      clearance after open heart surgery in neonates and young infants can serve as an
      early indicator of surgical success or AKI. METHODS: We conducted a prospective
      observational study in 19 neonates and small infants (body weight < 5 kg)
      scheduled for open heart surgery with cardiopulmonary bypass. Urine collection
      measurement of creatinine clearance and albumin excretion was performed before
      and during surgery and four times during 48 hours after surgery. RESULTS: Mean
      creatinine clearance was lowest during surgery (25.2 +/- 4. ml/min/1.73 m2) and
      increased significantly in the first 16 hours post-surgery (45.7 +/- 6.3
      ml/min/1.73 m2). A similar pattern was noted for urine albumin which was highest
      during surgery (203 +/- 31 ug/min) and lowest (93 +/- 20 ug/min) 48 hours post
      surgery. AKI occurred in four patients, and two patients even required dialysis.
      All six showed a decline in creatinine clearance and an increase in urine albumin
      between 8 and 16 hours post-surgery. CONCLUSIONS: In neonates and small infants
      undergoing open heart surgery, a significant improvement in creatinine clearance
      in the first 16 hours postoperatively is indicative of a good surgical outcome.
      This finding has important implications for the early evaluation and treatment of
      patients in the intensive care unit on the first day post-surgery.

PMID- 28457077
TI  - Lymphocyte Subset Reference Ranges in Healthy Israeli Adults.
AB  - BACKGROUND: Reference ranges for adult peripheral blood lymphocyte subsets have
      been established in a few countries. To the best of our knowledge no broad
      lymphocyte subset analysis of the Israeli population has been reported. 
      Objectives: To establish reference ranges for healthy adults in Israel and to
      describe age- and gender-specific differences, if present. OBJECTIVES: To
      establish reference ranges for healthy adults in Israel and to describe age- and
      gender-specific differences, if present. METHODS: Lymphocyte subsets CD3,
      CD3/CD4, CD3/CD8, CD3-/CD16+/CD56+, CD3/TCRalphabeta, CD3/TCRgammadelta, and CD19
      were examined by flow cytometry in 326 subjects. Samples were subdivided
      according to age and gender. RESULTS: Women of all ages had a significantly
      higher percentage and absolute counts of CD3/CD4 cells than their male
      counterparts. Higher CD3/CD4 cells were observed also in the older population (>
      50 years). CD3/CD8 and CD3-/CD16+/CD56+ were higher in males. Older males had a
      lower total lymphocyte percentage and CD19 cells compared to younger men. No
      significant gender-related differences were observed in percent and number of
      CD19, CD3/TCRalphabeta or CD3/TCRgammadelta at all ages. CONCLUSIONS: These
      reference values could be useful in further studies for assessing changes that
      occur in different populations in human pathology.

PMID- 28457078
TI  - Postoperative Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery
      Predicts Long-Term Atrial Fibrillation and Stroke.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common complication of coronary artery
      bypass graft (CABG) surgery, occurring in 20%-40% of patients, mostly during the
      first week after surgery. It is associated with increased morbidity and
      mortality, but data are limited. OBJECTIVES: To assess the correlation between
      new-onset in-hospital AF following CABG and long-term AF, cerebrovascular
      accident (CVA), or death. METHODS: We conducted an analysis of 161 consecutive
      patients who underwent isolated CABG surgery in a tertiary center during the
      period 2002-2003. RESULTS: Patients' mean age was 72 years, and the majority were
      males (77%). Approximately half of the patients experienced prior myocardial
      infarction, and 14% had left ventricular ejection fraction < 40%. Postoperative
      AF (POAF) occurred in 27% of the patients. Patients were older and had larger
      left atrium diameter. POAF was strongly correlated with late AF (OR 4.34, 95%CI
      1.44-13.1, P = 0.01) during a mean follow-up of 8.5 years. It was also correlated
      with long-term stroke but was not associated with long-term mortality.
      CONCLUSIONS: POAF is a common complication of CABG surgery, which is correlated
      with late AF and stroke. Patients with POAF should be closely monitored to
      facilitate early administration of anticoagulant therapy in a high risk
      population upon recurrence of AF.

PMID- 28457079
TI  - Evolving Concepts in Systemic Lupus Erythematosus.

PMID- 28457080
TI  - The Ongoing Debate regarding Long-Term Safety of Silicone Breast Augmentation
      Rages.

PMID- 28457081
TI  - Willie Sutton Strikes Again.

PMID- 28457082
TI  - "The Girl who Grew Horns": Temporal Swelling as an Atypical Presenting Symptom of
      Epstein-Barr Virus Infection.

PMID- 28457083
TI  - Intravenous immunoglobulin for Pediatric Neuropsychiatric Lupus Triggered by
      Epstein-Barr Virus Cerebral Infection.

PMID- 28457084
TI  - May-Thurner Syndrome.

PMID- 28457085
TI  - A Rare Case of Spontaneous Hemopneumothorax due to Left Subclavian Artery Tear.

PMID- 28457086
TI  - Letters.

PMID- 28457087
TI  - Savage War Injuries: the Alleviation of Suffering.

PMID- 28457088
TI  - Feasibility of Bedside Bowel Ultrasound Performed by a Gastroenterologist for
      Detection and Follow-Up of Inflammatory Bowel Disease.
AB  - BACKGROUND: Bowel ultrasound has several possible uses in inflammatory bowel
      disease (IBD), including the initial evaluation of suspected IBD, monitoring of
      therapeutic response, detection of relapse, and diagnosis of complications as
      well as of extra-intestinal manifestations. However, its use has been limited
      mainly to countries where it is performed by the attending physician. OBJECTIVES:
      To investigate the feasibility and sensitivity of bedside bowel ultrasound
      performed by a gastroenterologist for assessing disease activity and
      complications in IBD. METHODS: We performed a feasibility study to compare the
      results of bowel ultrasound examination with those of another cross-sectional
      imaging modality (computed tomographic enterography or magnetic resonance
      enterography) in Crohn's disease, or with colonoscopy in ulcerative colitis.
      RESULTS: Between May 2015 and March 2016, 178 bowel ultrasound examinations were
      performed in 178 patients with suspected or established diagnosis of IBD. In 79
      cases the results of another cross-sectional imaging or endoscopic examination
      performed within 3 months prior to the ultrasound exam were available. The
      sensitivity for detection of intestinal bowel thickening (a surrogate of
      inflammation) was 90%, and for detection of Crohn's disease complications, namely
      bowel stenosis and inflammatory mass, was 94% and 75%, respectively. CONCLUSIONS:
      Bowel ultrasound is a useful and feasible bedside imaging tool for the detection
      of inflammation and complications in IBD patients. Bedside bowel ultrasound can
      be a valuable non-invasive tool to assess disease activity and complications in
      IBD patients when performed by the attending physician.

PMID- 28457089
TI  - Immunogenicity of Sci-B-Vac (a Third-Generation Hepatitis B Vaccine) in HIV
      Positive Adults.
AB  - BACKGROUND: Guidelines recommend hepatitis B virus (HBV) vaccination of all
      adults positive for human immunodeficiency virus (HIV). Immune responses to
      single-antigen HBV vaccine among HIV-positive patients are low when compared with
      HIV-negative adults. Sci-B-VacTM is a recombinant third-generation HBV that may
      be advantageous in this population. OBJECTIVES: To examine the immune responses
      to Sci-B-Vac among HIV-positive adults. METHODS: We conducted a prospective
      cohort study involving HIV-positive adults who had negative HBV serology (HBSAg,
      HBSAb, HBcoreAb). Sci-B-Vac at 10 ug/dose was administered intramuscularly upon
      recruitment and after 1 and 6 months. HBSAb levels were checked 1 month after
      each dose; a level > 10 mlU/ml was considered protective. Data regarding age,
      gender, CD4 level, and viral load were collected. RESULTS: The study group
      comprised 31 patients. Average CD4 count was 503 +/- 281 cells/ml, and average
      viral load was 44 copies/ml. Median interquartile range (IQR) HBVAb titers after
      the first, second and third immunizations were 0 (0, 3.5), 30 (6, 126) and 253
      (81, 408) mlU/ml. Significant titer elevations were found between the second and
      third immunizations (P = 0.0003). The rate of patients considered protected was
      16% after the first, 65% after the second (P < 0.0001), and 84% after the third
      dose (P = 0.045). No adverse events were reported. More patients under the age of
      40 years responded to the first immunization (28% vs. 0%, P = 0.038). CD4 level
      had no influence on immunization rates. CONCLUSIONS: Sci-B-Vac might achieve
      better immunization rates among HIV-positive adults compared to the single
      antigen vaccine and thus deserves further evaluation in a randomized, double
      blind study in this population.

PMID- 28457090
TI  - Clinical and Microbiological Outcomes of Asymptomatic Bacteriuria in Elderly
      Stroke Patients.
AB  - BACKGROUND: The optimal approach to the evaluation of asymptomatic bacteruria in
      stroke patients is uncertain. OBJECTIVES: To compare elderly patients after an
      acute stroke with and without asymptomatic bacteriuria for the development of
      symptomatic urinary tract infections (UTI). METHODS: We prospectively monitored
      patients over 65 years of age admitted to our rehabilitation hospital after an
      acute stroke, with and without asymptomatic bacteriuria, for the development of
      symptomatic UTIs. The prevalence of bacteriuria was determined by urine cultures
      obtained 2 and 4 weeks after admission. Patients with and without persistent
      bacteriuria were compared to identify variables associated with bacteriuria.
      RESULTS: Fifty-five patients were included in the study. The prevalence of
      asymptomatic bacteriuria at baseline was 20%. Of all 55 stroke patients, 13
      (23.6%) developed a symptomatic UTI during the 30 day follow-up. Patients with
      stroke and asymptomatic bacteriuria at baseline had an increased risk of
      developing a symptomatic UTI (54.5% with asymptomatic bacteriuria vs. 15.9%
      without, P = 0.011). To exclude the effects of several confounders, we performed
      multivariate Cox regression analysis, which showed that bacteruria remained a
      significant covariate for symptomatic UTI (hazard ratio 2.86, 95% confidence
      interval 0.71-10.46, P = 0.051). When subjects who experienced symptomatic
      urinary infection were included, the prevalence of bacteriuria in the study
      cohort declined to about 45.5% by 30 days. CONCLUSIONS: Elderly patients with
      stroke and asymptomatic bacteriuria have an increased risk of developing a
      symptomatic UTI compared to those without asymptomatic bacteriuria during a 30
      day post-stroke follow-up.

PMID- 28457091
TI  - Corneal Staining and Hot Black Tea Compresses.
AB  - BACKGROUND: Warm compresses are widely touted as an effective treatment for
      ocular surface disorders. Black tea compresses are a common household remedy,
      although there is no evidence in the medical literature proving their effect and
      their use may lead to harmful side effects. OBJECTIVES: To describe a case in
      which the application of black tea to an eye with a corneal epithelial defect led
      to anterior stromal discoloration; evaluate the prevalence of hot tea compress
      use; and analyze, in vitro, the discoloring effect of tea compresses on a model
      of a porcine eye. METHODS: We assessed the prevalence of hot tea compresses in
      our community and explored the effect of warm tea compresses on the cornea when
      the corneal epithelium's integrity is disrupted. An in vitro experiment in which
      warm compresses were applied to 18 fresh porcine eyes was performed. In half the
      eyes a corneal epithelial defect was created and in the other half the epithelium
      was intact. Both groups were divided into subgroups of three eyes each and
      treated experimentally with warm black tea compresses, pure water, or chamomile
      tea compresses. We also performed a study in patients with a history of tea
      compress use. RESULTS: Brown discoloration of the anterior stroma appeared only
      in the porcine corneas that had an epithelial defect and were treated with black
      tea compresses. No other eyes from any group showed discoloration. Of the
      patients included in our survey, approximately 50% had applied some sort of tea
      ingredient as a solid compressor or as the hot liquid. CONCLUSIONS: An intact
      corneal epithelium serves as an effective barrier against tea-stain
      discoloration. Only when this layer is disrupted does the damage occur.
      Therefore, direct application of black tea (Camellia sinensis) to a cornea with
      an epithelial defect should be avoided.

PMID- 28457092
TI  - Transcatheter Tricuspid Valve-In-Valve Implantation in Patients with Tricuspid
      Bioprosthetic Valve Degeneration at High Surgical Risk: A Multicenter Case
      Series.
AB  - BACKGROUND: Transcatheter tricuspid valve-in-valve implantation (TVIV) is an
      attractive yet under-explored alternative to redo valve surgery. OBJECTIVES: To
      report the multicenter TVIV experience in Israel. METHODS: We approached multiple
      centers and collected data regarding seven TVIV cases. RESULTS: The study group
      comprised seven participants: five females and two males, with a mean age of 63
      +/- 12 years and EuroSCORE-II 13.6 +/- 3.3%. Follow-up ranged from 3 to 21 months
      (mean 8 +/- 6 months). All presented with advanced heart failure. The indication
      for valve intervention was a predominant tricuspid stenosis in three patients,
      significant tricuspid regurgitation in one and a mixture in three. Six procedures
      were conducted via a transfemoral approach and one by transatrial access. The
      Edwards SAPIENTM XT valve was used in four cases and the SAPIENTM 3 in three.
      Without pre-stenting/rapid pacing, all participants underwent successful valve
      implantation. Mean transvalvular gradient decreased from 11 +/- 3 mmHg to 6 +/- 3
      mmHg (P = 0.003) and regurgitation decreased from moderate/severe (in four cases)
      to none/trace (in six of the seven cases). One patient remained severely
      symptomatic and died 3.5 months after the implantation. All others achieved a
      functional capacity improvement and amelioration of symptoms soon after the
      implantation, which persisted during follow-up. CONCLUSIONS: TVIV may be a safe
      and effective strategy to treat carefully selected patients with degenerated
      bioprosthetic tricuspid valve at high operative risk.

PMID- 28457093
TI  - Deliberate Self-Harm in Older Adults: A General Hospital Emergency Department
      Survey.
AB  - BACKGROUND: Deliberate self-harm (DSH) increases the danger of future suicide
      death and the risk increases with age. Self-harm in older adults is often
      associated with greater suicidal intent and lethality. OBJECTIVES: To investigate
      clinical and psychosocial variables of older patients (age >= 65 years) assessed
      due to DSH, compared with younger adults. METHODS: Patients admitted to the
      Emergency Department following DSH during an 8 year period were included.
      RESULTS: Of 1149 participants, 187 (16.6%) were older adults (age >= 65) and 962
      (83.4%) were younger adults (< 65). The older adults reported DSH closer to mid
      day (P < 0.01) and suffered more frequently from adjustment disorder and
      depression. Personality disorders and schizophrenia were less commonly diagnosed
      (P < 0.001). Prescription medication (sedatives and hypnotics) were a more
      frequent means (88% vs. 71%) of DSH among older patients. Younger patients with
      DSH used over-the-counter medications (21.9% vs. 6.4%) three times more than did
      the older patients (P < 0.01). Past DSH was significantly more frequent in
      younger adults. Following DSH the older patients were frequently admitted for
      further general hospitalization (P < 0.001). CONCLUSIONS: Older adults with DSH
      are a unique group with different clinical characteristics. There is a need for
      targeted prevention strategies and education of caregivers regarding DSH in older
      adults.

PMID- 28457094
TI  - High Incidence of Carcinosarcoma among Patients Previously Treated with
      Tamoxifen.
AB  - BACKGROUND: Tamoxifen acts as an estrogen antagonist within the breast tissue. In
      the uterus, tamoxifen is an agonist for some estrogen receptors and therefore can
      cause hyperplasia or neoplasia in the endometrium. OBJECTIVES: To compare
      characteristics of patients with uterine sarcoma who were and were not previously
      treated with tamoxifen. METHODS: The medical records of all women with uterine
      sarcoma who had been treated at the Carmel Medical Center in Haifa, Israel,
      during 2000-2013 were retrospectively reviewed. Disease characteristics,
      histological type of sarcoma, patient demographics, treatments and final outcomes
      were compared between patients who had and those who had not been exposed to
      tamoxifen. RESULTS: Of the 66 patients identified, 14 (21%) had been exposed to
      tamoxifen, one of them for 3 years and 13 for at least 5 years. Mean ages were 69
      +/- 8 and 66 +/- 12 years for those exposed and those not exposed to the drug,
      respectively. Rates of uterine carcinosarcoma were 86% (12/14) and 44% (23/52),
      respectively (P < 0.006). Patients with carcinosarcoma were older than other
      sarcoma patients (73 +/- 7 vs. 59 +/- 11 P < 0.005).There were no statistically
      significant differences between the two groups in rates of diabetes mellitus,
      hypertension, dyslipidemia or heart disease. The mean time from diagnosis to
      death was 7.37 +/- 0.42 years. The overall survival rates of carcinosarcoma
      patients were not statistically different from that of other sarcoma patients.
      Tamoxifen exposure was not associated with overall survival among all sarcoma
      patients, nor among the subgroup of carcinosarcoma patients. CONCLUSIONS:
      Tamoxifen treatment was associated with elevated incidence of carcinosarcoma
      among women with uterine sarcoma, but was not found to be associated with
      prognosis or with co-morbidities.

PMID- 28457095
TI  - Cesarean Scar Pregnancy and Morbidly Adherent Placenta: Different or Similar?
AB  - BACKGROUND: Growing evidence suggests that cesarean scar pregnancy (CSP) and
      morbidly adherent placenta (MAP) may represent a continuum of the same disease.
      OBJECTIVES: To investigate and compare the prior risk factors in women with
      either CSP or MAP. METHODS: The study included 33 women diagnosed with CSP in our
      department between 2006 and 2014. For each CSP case, two pregnant patients with
      MAP were matched for hospitalization date from delivery ward records,
      constituting the control group. RESULTS: In both groups, maternal age, parity,
      and previous early and late abortions were similar. The rate of conception by
      assisted reproductive technologies was 9% in both groups. Although the number of
      previous cesarean sections was statistically different between CSP versus MAP
      (2.0 +/- 1.0 vs. 1.0 +/- 1.0, respectively, P = 0.006), the leading indication of
      previous cesarean section was breech presentation in both groups (28.1% and
      27.8%, respectively, P > 0.05). CONCLUSIONS: CSP and MAP share similar prior risk
      factors. Due to high morbidity in both diseases, further research is needed
      toward reducing the known etiological factors contributing to the growing number
      of both complications.

PMID- 28457096
TI  - Long Term Outcomes of MGuard Stent Deployment in Saphenous Vein Grafts and Native
      Coronary Arteries: A Single Center Experience.
AB  - BACKGROUND: The MGuardTM stent (InspireMD, Tel Aviv, Israel) is a bare metal mesh
      covered stent, developed to prevent no-reflow phenomenon during percutaneous
      coronary intervention (PCI) of saphenous vein grafts (SVG) and acute myocardial
      infarction (MI), both associated with significant atherothrombotic lesions.
      OBJECTIVES: To report on local experience with patients treated with the MGuard
      stent until follow-up at 1 year. METHODS: We followed 163 consecutive patients
      who underwent MGuard stent deployment during the period 2009 to 2014 in a large
      tertiary cardiac center in central Israel. RESULTS: The MGuard stent was used in
      67% of patients who underwent SVG-PCI while 33% were treated for native coronary
      artery disease, the majority during ST-elevation MI (STEMI). The mean age was 67
      years and 83% were males. The clinical presentation was STEMI in 30% and non
      STEMI/unstable angina in 60% of patients. Of the total number of patients, 47%
      had diabetes and 29% had chronic kidney disease. All patients had follow-up at 1
      year. Mortality in the native group was 1.9% vs. 10% in the vein graft cohort. ST
      was 2% in both groups. The major adverse cardiac event (MACE) rates were 11% in
      the native artery and 29% in the vein graft group, mainly due to respective
      target lesion revascularization/target vessel revascularization rates of 6% and
      7% in the native vessel group and 11% and 15% in the SVG group. CONCLUSIONS: In
      suitable patients undergoing SVG-PCI or native lesion intervention during acute
      MI, the MGuard stent is a viable treatment strategy. Its potential merits and
      limitations warrant further evaluation.

PMID- 28457098
TI  - Crystal-Induced Arthropathy in Elderly Patients Hospitalized for Acute
      Conditions.
AB  - BACKGROUND: Arthritis and arthralgia are painful symptoms experienced by many
      elderly patients during hospitalization. Crystal-induced arthritis (CIA) is one
      of the most common causes of arthritis worldwide and represents the most common
      cause of acute arthritis in the elderly. OBJECTIVES: To determine the incidence
      of both acute new onset or acute exacerbation of CIA among elderly patients
      hospitalized due to an acute medical illness. METHODS: This study comprised 85
      patients. Patients aged 70 years and older who complained of any articular pain
      were included in the study. Exclusion criteria were signs of septic arthritis,
      chronic use of steroids or non-steroidal anti-inflammatory drugs, or admission to
      the hospital due to an acute attack of CIA. RESULTS: RSynovial aspiration was
      performed in 76 patients (89%). Joint aspiration yielded a diagnosis in 67 of
      them (79%). The predominant type of crystal was calcium pyrophosphate dehydrate
      (68%) followed by monosodium urate (20%). The main causes of hospitalization were
      acute infectious disease (57%) followed by neurologic and cardiac diseases, 14%
      and 9% respectively, and orthopedic problems (6%). Among patients with acute
      infectious disease, the main causes were pulmonary (57%) and gastrointestinal
      (22%) infections. In 9 patients (12%) who underwent synovial aspiration, visible
      crystals were identified without a definite diagnosis. CONCLUSIONS: Our study
      showed that hospitalization could be a risk factor for the development of CIA,
      and the time to diagnose CIA is during hospitalization for other acute illnesses.

PMID- 28457097
TI  - Evaluation of the Effect of Heviz Mud in Patients with Hand Osteoarthritis: A
      Randomized, Controlled, Single-Blind Follow-Up Study.
AB  - BACKGROUND: Heat therapy is one of the most popular non-pharmacological
      treatments for osteoarthritis of the hand. OBJECTIVES: To investigate the
      therapeutic and chemical effects of Heviz mud on patients with hand
      osteoarthritis. METHODS: We randomly assigned 47 patients with mild-to-moderate
      hand osteoarthritis to two groups. Patients in group 1 (n=23) received Heviz mud
      applied directly to both hands, whereas patients in group 2 (n=24) also received
      mud to both hands, but nylon gloves separated the skin from the mud. Patients in
      both groups underwent five 20 minute treatment sessions per week for 3 weeks. The
      temperature of the mud was 42 degrees C. Outcome measures were Visual Analogue
      Scale (VAS) scores, hand grip strength, the number of swollen and tender joints
      of the hand, the duration of morning joint stiffness, Health Assessment
      Questionnaire score, and EuroQoL Group 5-Dimension Self-Report Questionnaire
      score. The study parameters were evaluated at baseline, immediately after
      treatment, and after 16 weeks. RESULTS: Both groups showed improvement in nearly
      all assessed parameters at the end of treatment and at 16 weeks from the start of
      treatment. At the week 16 follow-up visit, the patient group directly treated
      with mud showed significantly better improvement in VAS for II and IV parameters
      and in swollen joint count in both hands compared to the nylon glove-mud group.
      CONCLUSIONS: Heviz mud therapy significantly improved objective and subjective
      parameters in patients with hand osteoarthritis and had a beneficial effect on
      the patients' quality of life. Further studies are required to evaluate the
      chemical effects of the mud.

PMID- 28457099
TI  - The Autoimmune Tautology with a Focus on Systemic Sclerosis.

PMID- 28457100
TI  - Graves' Opthalmopathy.

PMID- 28457101
TI  - Autoimmune Tautology in a Complex Case of Polyautoimmunity: Systemic Sclerosis,
      Autoimmune Liver Involvement, Antiphospholipid Syndrome and Hashimoto's
      Thyroiditis.

PMID- 28457102
TI  - Delayed Hyperdense Ascites in a Peritoneal Dialysis Patient after Contrast
      Injection.

PMID- 28457103
TI  - Association between non-alcoholic fatty liver disease and hospitalized patients
      with community-acquired pneumonia.

PMID- 28457104
TI  - Delivery of Transverse-Lie Twins in a 15 year old Syrian Mother.

PMID- 28457105
TI  - Fifty years on: New lessons from Laron syndrome.

PMID- 28457106
TI  - Detection Rate and Sonographic Signs of Trisomy 21 Fetuses at 14-17 Weeks of
      Gestation.
AB  - BACKGROUND: Early prenatal ultrasound is an important part of prenatal screening
      in Israel. No studies have described the rate of trisomy 21 [T21] identification
      at 14-17 weeks gestation. OBJECTIVES: To describe the rate of T21 identification
      by transvaginal sonograms (TVS) at 14-17 weeks gestation. METHODS: We conducted a
      historical prospective study. Since 1986, early TVS of 72,000 fetuses at 14-17
      weeks gestation have been prospectively recorded together with prenatal screening
      data at a private ultrasound center (AL-KOL, Haifa). We calculated the fraction
      of T21 cases by dividing the total number of cases with abnormal sonographic
      findings by the total number of diagnosed T21 cases. We also examined the
      percentage of verified T21 cases that had completely normal prenatal screening
      tests prior to the early prenatal TVS, thus revealing the contribution of this
      examination to the existing prenatal screening. Fisher's exact test was used to
      calculate odds ratios for each sonographic marker. RESULTS: Of 137 T21 fetuses,
      123 had sonographic markers on early TVS, yielding a prediction capability of at
      least 89.87%. Of all T21 cases, 14% had completely normal nuchal
      translucency/first-trimester screening prior to the abnormal 14-17 week TVS
      findings. Isolated abnormal sonographic findings, which were found to increase
      the risk for T21, were common atrioventricular septal canal (odds ratio 88.88),
      duodenal atresia (OR 88.23), nuchal edema (OR 39.14), and hydrocephalus (OR
      15.78). Fetal hydronephrosis/pyelectasis was non-significant when isolated (OR
      1), and cardiac echogenic focus was associated with a decreased risk (OR 0.13).
      CONCLUSIONS: Early prenatal TVS at 14-17 weeks may identify almost 90% of T21 and
      adds 14% to the identification rate at the first-trimester screening.

PMID- 28457107
TI  - Congenital Absence of Salivary Glands in Fetuses with Trisomy 21.
AB  - BACKGROUND: The congenital absence of salivary glands has been reported in
      children but never in fetuses with trisomy 21. OBJECTIVES: To determine whether
      the congenital absence of salivary glands can be detected prenatally between 13
      and 16 weeks of gestation in normal and trisomy 21 fetuses using transvaginal
      ultrasound. METHODS: We performed a retrospective analysis of recordings of
      normal and trisomy 21 fetuses. Inclusion criteria were a single viable fetus and
      good visualization of the anatomic area of the salivary glands on both sides of
      the fetal face. All videos were reviewed by one examiner who reported the
      presence or absence of one or more salivary glands and was blinded to the fetal
      karyotype. RESULTS: Of the 45 videos reviewed, 4 were excluded from the study:
      namely, a non-viable fetus, twin pregnancy, and in 2 there was unsatisfactory
      visualization of the anatomic area of the salivary glands. Of the remaining 41
      fetuses, 24 had trisomy 21 and 17 were normal. In the trisomy 21 fetuses, 8
      (33.3%) had congenital absence of one or more salivary glands compared to 1 of 17
      normal fetuses (5.9%) (P < 0.05). CONCLUSIONS: Congenital absence of the salivary
      glands has a high specificity but low sensitivity for detecting trisomy 21
      fetuses.

PMID- 28457108
TI  - Syncope in Primary Prevention Implantable Cardioverter Defibrillator
      Implantation.
AB  - BACKGROUND: Syncope prognosis varies widely: 1 year mortality may range from 0%
      in the case of vasovagal events up to 30% in the presence of heart disease.
      OBJECTIVES: To assess the outcomes and prognosis of patients with implantable
      cardiac defibrillator (ICD) and indication of primary prevention and compare
      patients presenting with or without prior syncope. METHODS: We reviewed the
      charts of 75 patients who underwent ICD implantation with the indication of
      primary prevention and history of syncope and compared them to a control group of
      80 patients without prior syncope. We assessed the number of ventricular
      tachycardia (VT), ventricular fibrillation (VF), shock, anti-tachycardia pacing
      (ATP), and death in each group during the follow-up. RESULTS: Mean follow-up was
      893 days (810-976, 95% confidence interval) (no difference between groups).
      Patients with prior syncope had a higher ejection fraction (EF) (35.5 +/- 12.6
      vs. 31.4 +/- 8.76, P = 0.02), more episodes of VT (21.3% vs. 3.8%, P = 0.001) and
      VF (8% vs. 0%, P = 0.01) and also received more electric shocks (18.7% vs. 3.8%,
      P = 0.004) and ATP (17.3% vs. 6.2%, P = 0.031). There were no differences in
      inappropriate shocks (6.7% vs. 5%, P = 0.74), in cardiovascular mortality
      (cumulative 5 year estimate 29.9% vs. 32.2% P = 0.97) and any death (cumulative 5
      year estimate 38.1% vs. 48.9% P = 0.18) during the follow-up. CONCLUSIONS:
      Syncopal patients before ICD implantation seem to have more episodes of VT/VF and
      shock or ATP. No mortality differences were observed.

PMID- 28457109
TI  - Salvage Radiation Therapy for Biochemical Failure Following Radical
      Prostatectomy.
AB  - BACKGROUND: Radiotherapy to the prostate bed is used to eradicate residual
      microscopic disease following radical prostatectomy for prostate cancer.
      Recommendations are based on historical series. OBJECTIVES: To determine outcomes
      and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed.
      METHODS: We reviewed a prospective ethics committee-approved database of 229
      patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA)
      was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7-128). Treatment
      was planned and delivered using modern three-dimensional radiation techniques.
      Mean bioequivalent dose was 71 Gy (range 64-83 Gy). Progression was defined as
      two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up
      imaging, commencement of anti-androgen treatment for any reason, or death from
      prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was
      performed using STATA. RESULTS: Five year progression-free survival was 68%
      (95%CI 59.8-74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3
      0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate
      cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA
      value was the most important predictor of progression-free survival (HR 2.76, P <
      0.001). Daily image guidance was associated with reduced risk of gastrointestinal
      and genitourinary toxicity (P < 0.005). CONCLUSIONS: Contemporary SRT is
      associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml
      improves progression-free survival. Daily image guidance with online correction
      is associated with a decreased incidence of late toxicity.

PMID- 28457110
TI  - Nicotine Addiction and Withdrawal among Orthodox Jews: the Effect of Sabbath
      Abstinence.
AB  - BACKGROUND: Cigarette smoking is a widespread problem around the world. In
      Israel, the prevalence of smoking is 23%. Smokers who are Orthodox abstain from
      smoking during the Sabbath, i.e., from sundown Friday to sundown Saturday, due to
      a religious prohibition. The prevalence of smoking among Orthodox men is 13%.
      However, there are no data on patterns of smoking or on the addiction profiles in
      this population. OBJECTIVES: To explore the smoking patterns, motivation for
      smoking and nicotine addiction among Orthodox Jewish men, compared to non
      Orthodox men, as well as the differences in the urge to smoke and withdrawal
      symptoms on Saturday versus weekdays in the Orthodox group. METHODS: The
      participants completed the Fagerstrom test for nicotine dependence,
      questionnaires on reasons for smoking and smoking patterns, as well as two brief
      questionnaires on the urge to smoke and withdrawal symptoms after overnight
      abstinence on a weekday and after the end of the Sabbath. RESULTS: Both groups
      were strongly addicted to nicotine and there were no differences in the reasons
      for smoking, withdrawal symptoms and nicotine craving after an overnight
      abstinence on weekdays. However, religious smokers had low levels of craving for
      nicotine and few withdrawal symptoms during Sabbath abstinence when compared to
      weekdays. CONCLUSIONS: Although we found no difference in the baseline
      characteristics with regard to nicotine addiction, smoking motivation, urge to
      smoke and withdrawal symptoms between religious and non-religious groups, the
      former are able to abstain from smoking during 25 hours of the Sabbath every week
      with significantly fewer withdrawal symptoms compared to week days.

PMID- 28457111
TI  - Serum Tumor Necrosis Factor-Alpha Levels in Children with Nephrotic Syndrome: A
      Pilot Study.
AB  - BACKGROUND: Several studies link the pathogenesis of nephrotic syndrome to tumor
      necrosis factor-alpha (TNFalpha). However, data on the serum TNFalpha level in
      children with nephrotic syndrome are sparse. OBJECTIVES: To investigate serum
      TNFalpha levels and the effect of steroid therapy in children with nephrotic
      syndrome. METHODS: A prospective cohort pilot study of children with nephrotic
      syndrome and controls was conducted during a 1 year period. Serum TNFalpha levels
      were measured at presentation and at remission, or after a minimum of 80 days if
      remission was not achieved. RESULTS: Thirteen patients aged 2-16 years with
      nephrotic syndrome were compared with 12 control subjects. Seven patients had
      steroid-sensitive and six had steroid-resistant nephrotic syndrome. Mean baseline
      serum TNFalpha level was significantly higher in the steroid-resistant nephrotic
      syndrome patients than the controls (6.13 pg/ml vs. 4.36 pg/ml, P = 0.0483). Mean
      post-treatment TNFalpha level was significantly higher in the steroid-resistant
      than in the steroid-sensitive nephrotic syndrome patients (5.67 pg/ml vs. 2.14
      pg/ml, P = 0.001). In the steroid-resistant nephrotic syndrome patients, mean
      serum TNFalpha levels were similar before and after treatment. CONCLUSIONS:
      Elevated serum TNFalpha levels are associated with a lack of response to
      corticosteroids. Further studies are needed to investigate the role of TNFalpha
      in the pathogenesis of nephrotic syndrome.

PMID- 28457112
TI  - Iatrogenic Horner Syndrome: Etiology, Diagnosis and Outcomes.
AB  - BACKGROUND: The identification and prompt diagnosis of Horner syndrome (HS) is
      essential for preventing permanent damage. HS may arise when a lesion presents
      anywhere along the three-neuron oculosympathetic pathway that begins at the
      posterior-lateral nuclei of the hypothalamus all the way through to the orbit. We
      present four cases and review the literature to familiarize the reader with the
      identification, diagnosis and treatment of Horner syndrome. The four patients,
      three adults and one child, were followed for at least 6 months following the
      initial diagnosis (range 6-18 months). There was partial resolution in three of
      the four cases, while the fourth resolved completely. There are numerous causes
      of HS, some of them iatrogenic. While iatrogenic cases of HR are rare in both
      adults and children, HS is seen more often following surgical procedures. Prompt
      recognition of the syndrome and correction of the offending agent may prevent
      permanent damage to the neuronal pathway. It is therefore recommended that
      practitioners be aware of the risks for development of iatrogenic HS and the
      signs for early detection.

PMID- 28457113
TI  - Stereotactic Ablative Body Radiation for Stage I Lung Cancer in Israel: A
      Retrospective Single-Center Report.
AB  - BACKGROUND: Stereotactic ablative radiation therapy (SABR) is the application of
      a very high radiation dose to a small treatment volume. It is the new standard of
      care in medically inoperable early-stage lung cancer. OBJECTIVES: To report the
      outcomes of SABR in stage I lung cancer at Sheba Medical Center since its
      introduction in 2009. METHODS: We conducted a retrospective chart review of
      patients with stage I lung cancer treated during the period 2009-2015. Survival
      status was retrieved from the electronic medical records and confirmed with the
      national registry. Local failure was defined as increased FDG uptake on PETCT
      scan within a 2 cm radius of the treated region. Toxicity was estimated from
      medical records and graded according to common toxicity criteria for adverse
      events (CTCAE) version 4.03. Overall survival and local control were estimated by
      the Kaplan-Meier method. RESULTS: During the study period 114 patients were
      treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months
      (range 8.2-69.5 months), median age was 76 years. Eighty-two percent of the
      tumors were stage IA (size <= 3 cm). Median survival was 46 months; estimated 3
      year overall survival was 59% (95%CI 47-69%) and local control was 88% (95%CI 78
      94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in
      0.9%, grade 1-2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.
      CONCLUSIONS: SABR has been successfully implemented at Sheba Medical Center for
      the treatment of stage I lung cancer in inoperable patients. It is associated
      with excellent local control, minor toxicity and an acceptable overall survival.

PMID- 28457114
TI  - Anti-BLyS Treatment of 36 Israeli Systemic Lupus Erythematosus Patients.
AB  - BACKGROUND: Anti-BLyS treatment with the human belimumab monoclonal antibody was
      shown to be a safe and effective therapeutic modality in lupus patients with
      active disease (i.e., without significant neurological/renal involvement) despite
      standard treatment. OBJECTIVES: To evaluate the "real-life" safety and efficacy
      of belimumab added to standard therapy in patents with active lupus in five
      Israeli medical centers. METHODS: We conducted a retrospective open-labeled study
      of 36 lupus patients who received belimumab monthly for at least 1 year in
      addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA
      autoantibodies, chemistry, urinalysis and complete blood count) were done every 3
      4 months. Adverse events were obtained from patients' medical records. Efficacy
      assessment by the treating physicians was defined as excellent, good/partial, or
      no response. RESULTS: The study group comprised 36 lupus patients (8 males, 28
      females) with a mean age of 41.6 ?} 12.2 years. Belimumab was given for a mean
      period of 2.3 ?} 1.7 years (range 1-7). None of the patients discontinued
      belimumab due to adverse events. Four patients (11.1%) had an infection related
      to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of
      efficacy. The response was excellent in 25 patients (69.5%) and good/partial in
      the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and
      anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab
      treatment, there was a significant reduction in the usage of corticosteroids
      (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%).
      CONCLUSIONS: Belimumab, in addition to standard therapy, is a safe and effective
      treatment for active lupus patients.

PMID- 28457116
TI  - Second-Trimester Ultrasound for Adjusting Patient's Risk for Down Syndrome.

PMID- 28457115
TI  - Pseudoexfoliation: An Ocular Finding with Possible Systemic Implications.
AB  - BACKGROUND: Pseudoexfoliation syndrome (PES) is a common age-related disorder
      affecting 60-70 million people worldwide. Patients with PES have abnormal
      production and deposition of fibrillar material in the anterior chamber of the
      eye. These exfoliated fibrils, easily detected by ocular slit-lamp examination,
      have also been found to exist systematically in the skin, heart, lungs, liver and
      kidneys. Recently, myriad studies have associated PES with systemic conditions
      such as increased vascular risk, risk of dementia and inflammatory state. We
      review here the most current literature on the systemic implications of PES. Our
      aim is to encourage further studies on this important clinical entity.

PMID- 28457117
TI  - Is Syncope Always a Predictor of Unfavorable Outcome?

PMID- 28457118
TI  - Kounis Syndrome: Acute ST segment Elevation Myocardial Infarction following
      Allergic Reaction to Amoxicillin.

PMID- 28457119
TI  - The Importance of Trans-Thoracic Echocardiographic Suprasternal View in the
      Diagnosis and Treatment Follow-Up of Pulmonary Emboli.

PMID- 28457120
TI  - Fertility Treatments and Psychiatric Disorders: Ethical Considerations Regarding
      a Patient's Desire to Become a Mother.

PMID- 28457121
TI  - Infantile Osteopetrosis in a Kazakh Boy.

PMID- 28457122
TI  - Quantifying Inorganic Arsenic and Other Water-Soluble Arsenic Species in Human
      Milk by HPLC/ICPMS.
AB  - Because the toxicity of arsenic depends on its chemical form, risk assessments of
      arsenic exposure must consider the type of arsenic compound, and hence they
      require sensitive and robust methods for their determination. Furthermore, the
      assessment should include studies on the most vulnerable people within a
      population, such as newborns and infants, and thus there is a need to quantify
      arsenic species in human milk. Herein we report a method for the determination of
      arsenic species at low concentrations in human milk by HPLC/ICPMS. Comparison of
      single and triple quadrupole mass analysers showed comparable performance,
      although the triple quadrupole instrument more efficiently overcame the problem
      of ArCl+ interference, from the natural chloride present in milk, without the
      need for gradient elution HPLC conditions. The method incorporates a protein
      precipitation step with trifluoroacetic acid followed by addition of
      dichloromethane or dibromomethane to remove the lipids. The aqueous phase was
      subjected to anion-exchange and cation-exchange/mixed mode chromatography with
      aqueous ammonium bicarbonate and pyridine buffer solutions as mobile phases,
      respectively. For method validation, a human milk sample was spiked with defined
      amounts of dimethylarsinate, arsenobetaine, and arsenate. The method showed good
      recoveries (99-103%) with detection limits (in milk) in the range of 10 ng As kg
      1. The method was further tested by analyzing two Norwegian human milk samples
      where arsenobetaine, dimethylarsinate, and a currently unknown As species were
      found, but iAs was not detected.

PMID- 28457123
TI  - Simultaneous Catabolite Identification and Quantitation of Large Therapeutic
      Protein at the Intact Level by Immunoaffinity Capture Liquid Chromatography-High
      Resolution Mass Spectrometry.
AB  - As therapeutic recombinant fusion proteins become more widely applicable for the
      treatment of various types of diseases, there is an increased demand for
      universal methods such as liquid chromatography (LC)-mass spectrometry (MS) for
      the determination of their pharmacokinetic properties, particularly their
      catabolism. The most common approach of analyzing proteins by LC-MS is to digest
      them into peptides, which can serve as surrogates of the protein. Alternatively,
      we have developed a novel high-resolution mass spectrometry (HRMS) based approach
      for analyzing large-molecule proteins at the intact level in biological samples
      without digestion. We established an immunoaffinity capture LC-HRMS method to
      quantify the intact parent molecule while simultaneously identifying catabolites
      for recombinant fusion proteins. We describe this method using dulaglutide, a
      glucagon-like peptide 1 (GLP1)-Fc fusion protein. Two proteolytic sites within
      the GLP1 peptide sequence of dulaglutide were identified using this novel LC-HRMS
      analysis in vivo in mice. These proteolytic sites were identified with the intact
      molecule being quantified simultaneously. Together with the trypsin digestion
      based LC-MS/MS analysis using surrogate peptides from different domains of the
      analyte, an insightful understanding of the pharmacokinetics and in vivo
      biotransformation of dulaglutide was obtained. Thus, this method enables
      simultaneous acquisition of both intact drug concentration and important
      catabolite information for this recombinant fusion protein, providing valuable
      insight into the integrity of the molecule and its catabolism in vivo. This is
      critical for designing and screening novel protein therapeutics and for
      understanding their pharmacokinetics and pharmacodynamics. With continuing
      advancement of LC-HRMS and software, this method can be very beneficial in drug
      discovery and development.

PMID- 28457124
TI  - Porous Fe2O3 Nanoframeworks Encapsulated within Three-Dimensional Graphene as
      High-Performance Flexible Anode for Lithium-Ion Battery.
AB  - Integrating nanoscale porous metal oxides into three-dimensional graphene (3DG)
      with encapsulated structure is a promising route but remains challenging to
      develop high-performance electrodes for lithium-ion battery. Herein, we design
      3DG/metal organic framework composite by an excessive metal-ion-induced
      combination and spatially confined Ostwald ripening strategy, which can be
      transformed into 3DG/Fe2O3 aerogel with porous Fe2O3 nanoframeworks well
      encapsulated within graphene. The hierarchical structure offers highly
      interpenetrated porous conductive network and intimate contact between graphene
      and porous Fe2O3 as well as abundant stress buffer nanospace for effective charge
      transport and robust structural stability during electrochemical processes. The
      obtained free-standing 3DG/Fe2O3 aerogel was directly used as highly flexible
      anode upon mechanical pressing for lithium-ion battery and showed an ultrahigh
      capacity of 1129 mAh/g at 0.2 A/g after 130 cycles and outstanding cycling
      stability with a capacity retention of 98% after 1200 cycles at 5 A/g, which is
      the best results that have been reported so far. This study offers a promising
      route to greatly enhance the electrochemical properties of metal oxides and
      provides suggestive insights for developing high-performance electrode materials
      for electrochemical energy storage.

PMID- 28457125
TI  - Solubility of Calcium Phosphate in Concentrated Dairy Effluent Brines.
AB  - The solubility of calcium phosphate in concentrated dairy brine streams is
      important in understanding mineral scaling on equipment, such as membrane
      modules, evaporators, and heat exchangers, and in brine pond operation. In this
      study, the solubility of calcium phosphate has been assessed in the presence of
      up to 300 g/L sodium chloride as well as lactose, organic acids, and anions at
      10, 30, and 50  degrees C. As a neutral molecule, lactose has a marginal but
      still detectable effect upon calcium solubility. However, additions of sodium
      chloride up to 100 g/L result in a much greater increase in calcium solubility.
      Beyond this point, the concentrations of ions in the solution decrease
      significantly. These changes in calcium solubility can readily be explained
      through changes in the activity coefficients. There is little difference in
      calcium phosphate speciation between 10 and 30  degrees C. However, at 50 
      degrees C, the ratio of calcium to phosphate in the solution is lower than at the
      other temperatures and varies less with ionic strength. While the addition of
      sodium lactate has less effect upon calcium solubility than sodium citrate, it
      still has a greater effect than sodium chloride at an equivalent ionic strength.
      Conversely, when these organic anions are present in the solution in the acid
      form, the effect of pH dominates and results in much higher solubility and a
      calcium/phosphate ratio close to one, indicative of dicalcium phosphate dihydrate
      as the dominant solid phase.

PMID- 28457127
TI  - Microbial Secondary Metabolite, Phlegmacin B1, as a Novel Inhibitor of Insect
      Chitinolytic Enzymes.
AB  - Periodic chitin remodeling during insect growth and development requires a
      synergistic action of two glycosyl hydrolase (GH) family enzymes, GH18 chitinase
      and GH20 beta-N-acetylhexosaminidase (Hex). Inhibiting either or both of these
      enzymes is a promising strategy for pest control and management. In this study,
      OfChi-h (a GH18 chitinase) and OfHex1 (a GH20 Hex) from Ostrinia furnacalis were
      used to screen a library of microbial secondary metabolites. Phlegmacin B1 was
      found to be the inhibitor of both OfChi-h and OfHex1 with Ki values of 5.5 MUM
      and 26 MUM, respectively. Injection and feeding experiments demonstrated that
      phlegmacin B1 has insecticidal effect on O. furnacalis's larvae. Phlegmacin B1
      was predicted to bind to the active pockets of both OfChi-h and OfHex1.
      Phlegmacin B1 also showed moderate inhibitory activities against other bacterial
      and insect GH18 enzymes. This work provides an example of exploiting microbial
      secondary metabolites as potential pest control and management agents.

PMID- 28457126
TI  - Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron
      Enzyme AurF.
AB  - Binuclear non-heme iron enzymes activate O2 for diverse chemistries that include
      oxygenation of organic substrates and hydrogen atom abstraction. This process
      often involves the formation of peroxo-bridged biferric intermediates, only some
      of which can perform electrophilic reactions. To elucidate the geometric and
      electronic structural requirements to activate peroxo reactivity, the active
      peroxo intermediate in 4-aminobenzoate N-oxygenase (AurF) has been characterized
      spectroscopically and computationally. A magnetic circular dichroism study of
      reduced AurF shows that its electronic and geometric structures are poised to
      react rapidly with O2. Nuclear resonance vibrational spectroscopic definition of
      the peroxo intermediate formed in this reaction shows that the active
      intermediate has a protonated peroxo bridge. Density functional theory
      computations on the structure established here show that the protonation
      activates peroxide for electrophilic/single-electron-transfer reactivity. This
      activation of peroxide by protonation is likely also relevant to the reactive
      peroxo intermediates in other binuclear non-heme iron enzymes.

PMID- 28457128
TI  - Matrix Extension and Multilaboratory Validation of Arsenic Speciation Method EAM
      S4.10 to Include Wine.
AB  - A multilaboratory validation (MLV) was performed to extend the U.S. Food and Drug
      Administration's (FDA) analytical method Elemental Analysis Manual (EAM) S4.10,
      High Performance Liquid Chromatography-Inductively Coupled Plasma-Mass
      Spectrometric Determination of Four Arsenic Species in Fruit Juice, to include
      wine. Several method modifications were examined to optimize the method for the
      analysis of dimethylarsinic acid, monomethylarsonic acid, arsenate (AsV), and
      arsenite (AsIII) in various wine matrices with a range of ethanol concentrations
      by liquid chromatography-inductively coupled plasma-mass spectrometry. The
      optimized method was used for the analysis of five wines of different
      classifications (red, white, sparkling, rose, and fortified) by three
      laboratories. Additionally, the samples were fortified in duplicate at levels of
      approximately 5, 10, and 30 MUg kg-1 and analyzed by each participating
      laboratory. The combined average fortification recoveries of dimethylarsinic
      acid, monomethylarsonic acid, and inorganic arsenic (iAs the sum of AsV and
      AsIII) in these samples were 101, 100, and 100%, respectively. To further
      demonstrate the method, 46 additional wine samples were analyzed. The total As
      levels of all the wines analyzed in this study were between 1.0 and 38.2 MUg kg
      1. The overall average mass balance based on the sum of the species recovered
      from the chromatographic separation compared to the total As measured was 89%
      with a range of 51-135%. In the 51 analyzed samples, iAs accounted for an average
      of 91% of the sum of the species with a range of 37-100%.

PMID- 28457129
TI  - Structural Changes in Barley Protein LTP1 Isoforms at Air-Water Interfaces.
AB  - We use a coarse-grained model to study the conformational changes in two barley
      proteins, LTP1 and its ligand adduct isoform LTP1b, that result from their
      adsorption to the air-water interface. The model introduces the interface through
      hydropathy indices. We justify the model by all-atom simulations. The choice of
      the proteins is motivated by making attempts to understand formation and
      stability of foam in beer. We demonstrate that both proteins flatten out at the
      interface and can make a continuous stabilizing and denser film. We show that the
      degree of the flattening depends on the protein (the layers of LTP1b should be
      denser than those of LTP1) and on the presence of glycation. It also depends on
      the number (<=4) of the disulfide bonds in the proteins. The geometry of the
      proteins is sensitive to the specificity of the absent bonds. We provide
      estimates of the volume of cavities of the proteins when away from the interface.

PMID- 28457130
TI  - Azide-Modified Membrane Lipids: Synthesis, Properties, and Reactivity.
AB  - In the present work, we describe the synthesis and the temperature-dependent
      behavior of photoreactive membrane lipids as well as their capability to study
      peptide/lipid interactions. The modified phospholipids contain an azide group
      either in the middle part or at the end of an alkyl chain and also differ in the
      linkage (ester vs ether) of the second alkyl chain. The temperature-dependent
      aggregation behavior of the azidolipids was studied using differential scanning
      calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and small
      angle X-ray scattering (SAXS). Aggregate structures were visualized by stain and
      cryo transmission electron microscopy (TEM) and were further characterized by
      dynamic light scattering (DLS). We show that the position of the azide group and
      the type of linkage of the alkyl chain at the sn-2 position of the glycerol
      influences the type of aggregates formed as well as their long-term stability:
      P10AzSPC and r12AzSHPC show the formation of extrudable liposomes, which are
      stable in size during storage. In contrast, azidolipids that carry a terminal
      azido moiety either form extrudable liposomes, which show time-dependent vesicle
      fusion (P15AzPdPC), or self-assemble in large sheet-like, nonextrudable
      aggregates (r15AzPdHPC) where the lipid molecules are arranged in an
      interdigitated orientation at temperatures below Tm (LbetaI phase). Finally, a
      P10AzSPC:DMPC mixture was used for photochemically induced cross-linking
      experiments with a transmembrane peptide (WAL-peptide) to demonstrate the
      applicability of the azidolipids for the analysis of peptide/lipid interactions.
      The efficiency of photo-cross-linking was monitored by attenuated total
      reflection infrared (ATR-IR) spectroscopy and mass spectrometry (MS).

PMID- 28457131
TI  - Fast Prediction of CO Binding Energy via the Local Structure Effect on PtCu Alloy
      Surfaces.
AB  - CO poisoning is a major problem for Pt-based catalysts in various catalytic
      processes. Thus, the prediction of CO binding energies over Pt alloy surfaces is
      fundamentally important to evaluate their CO poisoning tolerance. This article
      describes the effect of surface and subsurface coordination environments on the
      CO binding strength over PtCu alloy surfaces by employing density functional
      theory calculations. We show that the existence of surface Pt neighbors weakens
      the CO binding strength on Pt, whereas the subsurface Pt neighbors play the
      opposite role. Crystal orbital Hamilton population analysis suggests a stronger
      antibonding interaction for the Ptsurface-Ptsubsurface bond than for the
      Ptsurface-Ptsurface bond, which indicates less stable subsurface Pt atoms that
      hence generate an activated surface Pt that attracts CO more strongly. On the
      basis of the calculated CO binding energies, an empirical formula, with Pt-Pt
      coordination numbers as the variables, has been fitted to achieve a fast
      prediction of CO binding energy over PtCu alloy surfaces.

PMID- 28457133
TI  - Impact of Mechanical and Thermal Energies on the Degradation of T-2 and HT-2
      Toxins during Extrusion Cooking of Oat Flour.
AB  - The type A trichothecenes T-2 toxin (T-2) and HT-2 toxin (HT-2) are naturally
      occurring toxic food contaminants, with the highest concentrations found in
      contaminated oats. The influence of thermal food processing on these toxins is
      poorly understood, and only a few publications address the degradation rates.
      Therefore, we systematically investigated the degradation of T-2 and HT-2 during
      both laboratory and industrial-scale extrusion cooking of oats. Extrusion cooking
      under laboratory conditions was performed with oats fortified with T-2 or HT-2 as
      well as with naturally contaminated oat flour dust. The experiments were designed
      according to industrial conditions in terms of temperature, water content,
      pressure, residence time, and oat content. Flour mixtures containing naturally
      contaminated oats were used for industrial-scale processing. Degradation rates
      under laboratory conditions were up to 59.6 +/- 1.51 and 47.2 +/- 0.53% for T-2
      and HT-2, respectively, in fortified extrudates but were decreased to 35.1 +/-
      1.55 and 22.0 +/- 4.68% when naturally contaminated flour samples were used. The
      results show a higher degradation of T-2 during extrusion cooking than of HT-2.
      Moisture content, mechanical shear, and temperature showed an impact on the toxin
      degradation and can be optimized to counteract food contamination.

PMID- 28457134
TI  - Alterations of the Benzoxazinoid Profiles of Uninjured Maize Seedlings During
      Freezing, Storage, and Lyophilization.
AB  - Benzoxazinoids are highly studied compounds due to their biological activity and
      presence in several cereals. They include compound classes such as hydroxamic
      acids and lactams and usually occur as inactive glucosides in unstressed plants.
      Injury to the plant causes enzymatic hydrolysis of the inactive glucosides to the
      biologically active hydroxamic acid and lactam aglucones. The hydroxamic acids
      further undergo spontaneous hydrolysis to benzoxazolinones in aqueous solution.
      Extraction methods that do not cause immediate inactivation of enzymes result in
      accumulation of aglucones in samples. Using HPLC-MS to profile benzoxazinoids in
      maize seedlings subjected to several sample preparation techniques, we have found
      that hydroxamic acid aglucones and benzoxazolinones are present in uninjured
      maize seedlings, but that the benxozazinoid profile varies depending on sample
      treatment, potentially underrepresenting the glucoside content and
      overrepresenting the aglucone and benzoxazolinone content.

PMID- 28457132
TI  - Analysis of Photoirradiated Water Accommodated Fractions of Crude Oils Using
      Tandem TIMS and FT-ICR MS.
AB  - For the first time, trapped ion mobility spectrometry (TIMS) in tandem with
      Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is
      applied to the analysis of the low energy water accommodated fraction (WAF) of a
      crude oil as a function of the exposure to light. The TIMS-FT-ICR MS analysis
      provided, in addition to the heteroatom series identification, new insights into
      the WAF isomeric complexity (e.g., [m/z; chemical formula; collision cross
      section] data sets) for a better evaluation of the degree of chemical and
      structural photoinduced transformations. Inspection of the [m/z; chemical
      formula; collision cross section] data sets shows that the WAF composition
      changes as a function of the exposure to light in the first 115 h by initial
      photosolubilization of HC components and their photo-oxidation up to O4-5 of
      mainly high double bond equivalence species (DBE > 9). The addition of high
      resolution TIMS (resolving power of 90-220) to ultrahigh resolution FT-ICR MS
      (resolving power over 400k) permitted the identification of a larger number of
      molecular components in a single analysis (e.g., over 47k using TIMS-MS compared
      to 12k by MS alone), with instances of over 6-fold increase in the number of
      molecular features per nominal mass due to the WAF isomeric complexity. This work
      represents a stepping stone toward a better understanding of the WAF components
      and highlights the need for better experimental and theoretical approaches to
      characterize the WAF structural diversity.

PMID- 28457135
TI  - Plasmonic Photothermal Gold Bipyramid Nanoreactors for Ultrafast Real-Time
      Bioassays.
AB  - Nucleic acid amplification techniques have been among the most powerful tools for
      biological and biomedical research, and the vast majority of the bioassays rely
      on thermocycling that uses time-consuming and expensive Peltier-block heating.
      Here, we introduce a plasmonic photothermal method for quantitative real-time
      PCR, using gold bipyramids and light to achieve ultrafast thermocycling.
      Moreover, we successfully extend our photothermal system to other biological
      assays, such as isothermal nucleic acid amplification and restriction enzyme
      digestion.

PMID- 28457136
TI  - Screening for Polar Chemicals in Water by Trifunctional Mixed-Mode Liquid
      Chromatography-High Resolution Mass Spectrometry.
AB  - The presence of persistent and mobile organic contaminants (PMOC) in aquatic
      environments is a matter of high concern due to their capability of crossing
      through natural and anthropogenic barriers, even reaching drinking water. Most
      analytical methods rely on reversed-phase liquid chromatography (RPLC), which is
      quite limited for the detection of very polar chemicals. Thus, many of these
      PMOCs may have not been recognized as water pollutants yet, due to the lack of
      analytical methods capable to detect them. Mixed-mode LC (MMLC), providing the
      combination of RP and ion-exchange functionalities is explored in this work with
      a trifunctional column, combining RPLC, anion and cation exchange, which allows
      the simultaneous determination of analytes with extremely different properties. A
      nondiscriminant sample concentration step followed by a MMLC-high resolution mass
      spectrometry method was developed for a group of 37 very polar model chemicals
      with different acid/base functionalities. The overall method performance was
      satisfactory with a mean limit of detection of 50 ng/L, relative standard
      deviation lower than 20% and overall recoveries (including matrix effects) higher
      than 60% for 54% of model compounds. Then, the method was applied to 15 real
      water samples, by a suspect screening approach. For those detected PMOC with
      standard available, a preliminary estimation of concentrations was also
      performed. Thus, 22 compounds were unequivocally identified in a range of
      expected concentrations from 6 ng/L to 540 MUg/L. Some of them are well-known
      PMOC, such as acesulfame, perfluorobutanoic acid or metformin, but other novel
      pollutants were also identified, as for example di-o-tolylguanidine or
      trifluoromethanesulfonic acid, which had not or were scarcely studied in water so
      far.

PMID- 28457137
TI  - Study of Pinch-Off Locations during Drop-on-Demand Inkjet Printing of
      Viscoelastic Alginate Solutions.
AB  - The ligament pinch-off process of viscoelastic fluids during jetting is a key
      step in various biotechnology and dropwise three-dimensional printing
      applications. Various pinch-off locations have been investigated as a function of
      material properties and operating conditions during the drop-on-demand (DOD)
      inkjet printing of viscoelastic alginate solutions. Four breakup types are
      identified on the basis of the location of the first pinch-off position: front
      pinching is mainly governed by a balance of inertial and capillary effects, exit
      pinching is affected by the external actuation-induced hydrodynamic instability
      and mainly governed by a balance of elastic and capillary effects, middle
      pinching usually occurs any place along a uniform thin ligament under dominant
      viscous and elastic effects, and hybrid pinching happens when front pinching and
      exit pinching occur simultaneously as a special case.

PMID- 28457138
TI  - Near-Perfect Spin Filtering and Negative Differential Resistance in an Fe(II)S
      Complex.
AB  - Density functional theory and nonequilibrium Green's function calculations have
      been used to explore spin-resolved transport through the high-spin state of an
      iron(II)sulfur single molecular magnet. Our results show that this molecule
      exhibits near-perfect spin filtering, where the spin-filtering efficiency is
      above 99%, as well as significant negative differential resistance centered at a
      low bias voltage. The rise in the spin-up conductivity up to the bias voltage of
      0.4 V is dominated by a conductive lowest unoccupied molecular orbital, and this
      is accompanied by a slight increase in the magnetic moment of the Fe atom. The
      subsequent drop in the spin-up conductivity is because the conductive channel
      moves to the highest occupied molecular orbital, which has a lower conductance
      contribution. This is accompanied by a drop in the magnetic moment of the Fe
      atom. These two exceptional properties, and the fact that the onset of negative
      differential resistance occurs at low bias voltage, suggests the potential of the
      molecule in nanoelectronic and nanospintronic applications.

PMID- 28457139
TI  - Optimizing the Formation of Supported Lipid Bilayers from Bicellar Mixtures.
AB  - Supported lipid bilayers (SLBs) are widely studied model membrane platforms that
      are compatible with various surface-sensitive measurement techniques. SLBs are
      typically formed on silica-based materials, and there are numerous possible
      fabrication routes involving either bottom-up molecular self-assembly or vesicle
      adsorption and rupture. In between these two classes of fabrication strategies
      lies an emerging approach based on depositing quasi-two-dimensional lamellar,
      bicellar disks composed of a mixture of long-chain and short-chain phospholipids
      to promote the formation of SLBs. This approach takes advantage of the
      thermodynamic preference of long-chain phospholipids to form planar SLBs, whereas
      short-chain phospholipids have brief residence times. Although a few studies have
      shown that SLBs can be formed on silica-based materials from bicellar mixtures,
      outstanding questions remain about the self-assembly mechanism as well as the
      influence of the total phospholipid concentration, ratio of the two phospholipids
      (termed the "q-ratio"), and process of sample preparation. Herein, we address
      these questions through comprehensive quartz crystal microbalance-dissipation,
      fluorescence microscopy, and fluorescence recovery after photobleaching
      experiments. Our findings identify that optimal SLB formation occurs at lower
      total concentrations of phospholipids than previously used as short-chain
      phospholipids behave like membrane-destabilizing detergents at higher
      concentrations. Using lower phospholipid concentrations, we also discovered that
      the formation of SLBs proceeds through a two-step mechanism involving a critical
      coverage of bicellar disks akin to vesicle fusion. In addition, the results
      indicate that at least one cycle of freeze-thaw-vortexing is useful during the
      sample preparation process to produce SLBs. Taken together, the findings in this
      work identify optimal routes for fabricating SLBs from bicellar mixtures and
      reveal mechanistic details about the bicelle-mediated SLB formation process,
      which will aid further exploration of bicellar mixtures as tools for model
      membrane fabrication.

PMID- 28457140
TI  - Bioconjugate Therapeutics: Current Progress and Future Perspective.

PMID- 28457141
TI  - Toward Artificial Immunotoxins: Traceless Reversible Conjugation of RNase A with
      Receptor Targeting and Endosomal Escape Domains.
AB  - The specific transport of bioactive proteins into designated target cells is an
      interesting and challenging perspective for the generation of innovative
      biopharmaceuticals. Natural protein cytotoxins perform this task with outstanding
      efficacy. They enter cells with receptor-targeted specificity, respond to
      changing intracellular microenvironments, and by various mechanisms translocate
      their cytotoxic protein subunit into the cytosol. Here we imitate this toxin
      based delivery strategy in an artificial setting, by bioreversible conjugation of
      a cytotoxic cargo protein (RNase A) with receptor-targeting PEG-folate and the pH
      specific endosomolytic peptide INF7 as synthetic delivery domains. Covalent
      modification of the cargo protein was achieved using the pH-labile AzMMMan linker
      and copper-free click chemistry with DBCO-modified delivery modules. This linkage
      is supposed to enable traceless intracellular release of the RNase A after
      exposure to the endosomal weakly acidic environment. Delivery of RNase A via this
      polycation-free delivery strategy resulted in high cytotoxicity against receptor
      positive KB tumor cells only when both PEG-folate and INF7 were attached.

PMID- 28457142
TI  - Decision-making for tracheostomy in amyotrophic lateral sclerosis (ALS): a
      retrospective study.
AB  - BACKGROUND: ALS patients should discuss the issue of tracheostomy before the
      onset of terminal respiratory failure. While the process of shared decision
      making is desirable, there are few data on the practical application of this real
      life situation. AIM OF THE STUDY: To determine how a decision-making process is
      actually carried out, we analysed the episodes of acute respiratory failure
      preceding tracheostomy. METHODS: We studied the charts of a group of ALS patients
      after tracheostomy. An interview focusing on the existence of anticipated
      directives was carried out. Tracheostomies were classified as planned or
      unplanned according to the presence of a decision plan. RESULTS: A total of 209
      ALS patients were cared for during a three-year period. Of these patients, 34
      (16%) were tracheotomised. In 38% of cases, tracheostomy was planned, 41% were
      unplanned, and 21% remained undiagnosed. CONCLUSIONS: A minority of ALS patients
      make a voluntary decision for tracheostomy before the procedure is conducted. The
      advising process of care still presents limits that have been thus far poorly
      addressed. In the future, we will need to develop guidelines for the timing and
      content of the shared-decision making process.

PMID- 28457143
TI  - Typical Skin Injuries in Children With Autism Spectrum Disorder.
AB  - Pediatric skin injuries have primarily been described in typically developing
      children. Our objectives were to describe the prevalence and pattern of skin
      injuries of children with autism spectrum disorder (ASD), to describe how this
      compared with previously demonstrated skin injury locations in typically
      developing children, and to identify differences in skin injury frequency and
      locations between autistic children with and without self-injurious behaviors
      (SIBs). Children with ASD were recruited between September of 2011 and September
      of 2014. Demographic information was obtained from the caregiver. All skin
      injuries and their locations were documented. Of the 41 children enrolled, half
      were reported to have SIBs. The most identified skin injury locations were the
      legs, knees, and back. Children with autism (1) obtain skin injuries frequently
      and in similar locations as typically developing children and (2) rarely obtain
      skin injuries to locations that are considered uncommon for accidental injuries
      despite reports of SIBs.

PMID- 28457144
TI  - Molecular effects of hesperetin, a citrus flavanone on7,12
      dimethylbenz(a)anthracene induced buccal pouch squamous cell carcinoma in golden
      Syrian hamsters.
AB  - In recent years, researchers have been focused on citrus flavanone, a naturally
      occurring bioactive substance of hesperetin. To investigate the molecular
      mechanism based chemopreventive efficacy of hesperetin on 7,12
      dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch (HBP) squamous cell
      carcinoma (SCC). The oral tumour was provoked by painted with 0.5% DMBA on left
      buccal pouch thrice a week for 10 consecutive weeks developed well-differentiated
      SCC and tumour formation was 100% in DMBA alone. We evaluated the chemopreventive
      potential of hesperetin by assessing the lipid peroxidation (LPO) by-products,
      status of enzymatic, non-enzymatic antioxidants, detoxifying agents etc.
      Moreover, modulating expression of apoptotic and cell proliferation markers were
      observed in HBP SCC experimental hamsters. Oral administration of hesperetin (20
      mg/kg b.w.) to DMBA painted hamsters significantly reversed the stages of oral
      SCC. Our findings indicate that hesperetin possesses a chemopreventive effect in
      DMBA-induced oral SCC by exerting anti-carcinogenic property.

PMID- 28457145
TI  - Region-specific disruption of the blood-brain barrier following repeated
      inflammatory dural stimulation in a rat model of chronic trigeminal allodynia.
AB  - Background The blood-brain barrier (BBB) has been hypothesized to play a role in
      migraine since the late 1970s. Despite this, limited investigation of the BBB in
      migraine has been conducted. We used the inflammatory soup rat model of
      trigeminal allodynia, which closely mimics chronic migraine, to determine the
      impact of repeated dural inflammatory stimulation on BBB permeability. Methods
      The sodium fluorescein BBB permeability assay was used in multiple brain regions
      (trigeminal nucleus caudalis (TNC), periaqueductal grey, frontal cortex, sub
      cortex, and cortex directly below the area of dural activation) during the
      episodic and chronic stages of repeated inflammatory dural stimulation. Glial
      activation was assessed in the TNC via GFAP and OX42 immunoreactivity.
      Minocycline was tested for its ability to prevent BBB disruption and trigeminal
      sensitivity. Results No astrocyte or microglial activation was found during the
      episodic stage, but BBB permeability and trigeminal sensitivity were increased.
      Astrocyte and microglial activation, BBB permeability, and trigeminal sensitivity
      were increased during the chronic stage. These changes were only found in the
      TNC. Minocycline treatment prevented BBB permeability modulation and trigeminal
      sensitivity during the episodic and chronic stages. Discussion Modulation of BBB
      permeability occurs centrally within the TNC following repeated dural
      inflammatory stimulation and may play a role in migraine.

PMID- 28457146
TI  - Are women with polycystic ovary syndrome at increased cardiovascular disease risk
      later in life?
AB  - To date, the world's leading cause of death amongst women is cardiovascular
      disease. Polycystic ovary syndrome (PCOS) is associated with an unfavorable
      cardiometabolic profile in early life. Apart from dyslipidemia, obesity and onset
      of type 2 diabetes mellitus, androgens are thought to influence cardiovascular
      health. The question rises whether women with PCOS are truly at risk for
      cardiovascular disease in later life. In this review paper, we aim to reflect on
      this assumed relation based on studies in different stages of life in women with
      PCOS. Cardiovascular risk factors (type 2 diabetes mellitus, obesity and
      metabolic syndrome), surrogate outcomes (flow-mediated dilation, carotid intima
      media thickness and coronary artery calcium) and clinical long-term outcomes
      (cardiovascular disease and mortality) will be summarized. Data on cardiovascular
      disease and mortality in peri- and postmenopausal women with PCOS appear to be
      controversial. Whether androgens have a protective or unfavorable influence on
      the manifestation of cardiovascular disease remains uncertain. The need for
      large, prospective, well-phenotyped cohort studies of women with PCOS is high.
      Only then will we be able to answer this research question.

PMID- 28457147
TI  - Open Scientific Practices Are the Way Forward for Internet Gaming Disorder
      Research: Response to Yao et al.

PMID- 28457149
TI  - A Cruel Irony for Clinicians Who Treat Depression.

PMID- 28457151
TI  - Internet Gaming Disorder Within the DSM-5 Framework and With an Eye Toward ICD
      11.

PMID- 28457152
TI  - Current Progress in Opioid Treatment.

PMID- 28457153
TI  - The Role of Antipsychotic Plasma Levels in the Treatment of Schizophrenia.

PMID- 28457155
TI  - Quality Improvement in Neurology: Dementia Management Quality Measurement Set
      Update.

PMID- 28457157
TI  - Citalopram Discontinuation More Harmful Than Gradual Dosage Reduction?

PMID- 28457158
TI  - "I Hear You".

PMID- 28457159
TI  - The Suicide of Saul by Pieter Bruegel the Elder.

PMID- 28457161
TI  - Clarifying Methods in a Study of Outcomes of Citalopram Dosage Risk Mitigation in
      a Veteran Population: Response to Krijnsen et al.

PMID- 28457162
TI  - Swedish Register Analysis of Divorce and Alcohol Use Disorder Highlights Social
      Relationships as a Target for Preventive Psychiatry and Genetic Research.

PMID- 28457163
TI  - Antidepressant Pharmacogenetics.

PMID- 28457164
TI  - On the Magical Thinking Related to Mental Health in Chad.

PMID- 28457166
TI  - Conflict of Interest and FAI.

PMID- 28457165
TI  - Redox Changes During the Cell Cycle in the Embryonic Root Meristem of Arabidopsis
      thaliana.
AB  - AIMS: The aim of this study was to characterize redox changes in the nuclei and
      cytosol occurring during the mitotic cell cycle in the embryonic roots of
      germinating Arabidopsis seedlings, and to determine how redox cycling was
      modified in mutants with a decreased capacity for ascorbate synthesis. RESULTS:
      Using an in vivo reduction-oxidation (redox) reporter (roGFP2), we show that
      transient oxidation of the cytosol and the nuclei occurred at G1 in the
      synchronized dividing cells of the Arabidopsis root apical meristem, with
      reduction at G2 and mitosis. This redox cycle was absent from low ascorbate
      mutants in which nuclei were significantly more oxidized than controls. The cell
      cycle-dependent increase in nuclear size was impaired in the ascorbate-deficient
      mutants, which had fewer cells per unit area in the root proliferation zone. The
      transcript profile of the dry seeds and size of the imbibed seeds was strongly
      influenced by low ascorbate but germination, dormancy release and seed aging
      characteristics were unaffected. INNOVATION: These data demonstrate the presence
      of a redox cycle within the plant cell cycle and that the redox state of the
      nuclei is an important factor in cell cycle progression. CONCLUSIONS: Controlled
      oxidation is a key feature of the early stages of the plant cell cycle. However,
      sustained mild oxidation restricts nuclear functions and impairs progression
      through the cell cycle leading to fewer cells in the root apical meristem.
      Antioxid. Redox Signal. 27, 1505-1519.

PMID- 28457168
TI  - Tibial Nerve Palsy by a Crossing Posterior Tibial Artery Branch After Lateral
      Sliding Calcaneal Osteotomy.

PMID- 28457169
TI  - Arthroscopic Correlates of Subtle Syndesmotic Injury.
AB  - BACKGROUND: Arthroscopic criteria for identifying syndesmotic disruption have
      been variable and subjective. We aimed to quantify syndesmotic disruption
      arthroscopically using a standardized measurement device. METHODS: Ten cadaveric
      lower extremity specimens were tested in intact state and after serial sectioning
      of the syndesmotic structures (anterior inferior tibiofibular ligament [AiTFL],
      interosseous ligament [IOL], posterior inferior tibiofibular ligament [PiTFL],
      deltoid). Diagnostic ankle arthroscopy was performed after each sectioning.
      Manual external rotational stress was applied across the tibiofibular joint.
      Custom-manufactured spherical balls of increasing diameter mounted on the end of
      an arthroscopic probe were inserted into the tibiofibular space to determine the
      degree of diastasis of the tibiofibular joint under each condition. RESULTS: A
      ball 3 mm in diameter reliably indicated a high likelihood of combined disruption
      of the AiTFL and IOL. Disruption of the AiTFL alone could not be reliably
      distinguished from the intact state. CONCLUSION: Use of a spherical probe placed
      into the tibiofibular space during manual external rotation of the ankle provided
      an objective measure of syndesmotic instability. Passage of a 2.5-mm probe
      indicated some disruption of the syndesmosis, but the test had poor negative
      predictive value. Passage of a 3.0-mm spherical probe indicated very high
      likelihood of disruption of both the AiTFL and the IOL. CLINICAL RELEVANCE: The
      findings challenge the previously used but unsupported standard of a 2-mm
      diastasis of the tibiofibular articulation for diagnosis of subtle syndesmotic
      instability.

PMID- 28457170
TI  - An adult case of Kommerell's diverticulum with a right-sided aortic arch.
AB  - The patient was a 56-year-old woman with Kommerell's diverticulum associated with
      a right-sided aortic arch with mirror-image branching. No other congenital heart
      anomalies or vascular rings were observed. Descending aortic replacement through
      a right posterolateral thoracotomy was performed to eliminate the risk of
      diverticular rupture. The patient's postoperative course was uneventful. This was
      a rare adult case of right-sided aortic arch with Kommerell's diverticulum
      associated with no other congenital heart disease.

PMID- 28457171
TI  - The moving ball.

PMID- 28457172
TI  - A systematic surgical approach to hepatoblastoma with intracardiac extension.
AB  - Hepatoblastoma is very uncommon in children, and intracardiac extension is rare.
      The SIOPEL-4 regime for metastatic hepatoblastoma has extended the surgical
      options with good results. We successfully treated a boy aged 2 years and 9
      months with hepatoblastoma, using a multidisciplinary surgical strategy involving
      an extended left hepatectomy, left adrenalectomy, biopsy of the paraaortic and
      coeliac lymph nodes, and resection of the inferior vena caval-right atrial
      extension of the hepatoblastoma, under cardiopulmonary bypass and deep
      hypothermia.

PMID- 28457173
TI  - A survey on pulmonary thromboendarterectomy in the Asia-Pacific region.
AB  - Background Surgical pulmonary thromboendarterectomy has been established as the
      treatment of choice for chronic thromboembolic pulmonary hypertension. We
      conducted a survey among Asia-Pacific cardiothoracic surgeons to examine their
      current practice demographics and reflect their views on the future prospects for
      pulmonary thromboendarterectomy surgery. Methods All cardiothoracic surgeons who
      were registered on the CTSNet.org website and based in the Asia-Pacific region
      were invited to participate in an online survey. The electronic questionnaire was
      completed by 172 (6.3%) surgeons. Responses were recorded anonymously and
      tabularized as absolute figures and fractions. Results Pulmonary
      thromboendarterectomy surgery has been performed by few Asia-Pacific surgeons and
      in small numbers of patients, but survival rates and functional outcomes were
      satisfactory in most experiences. Failures were thought to have resulted
      primarily from the difficulty in selecting suitable candidates for surgery. The
      need for greater clinical experience was clear, yet this might be hampered by the
      limited recognition of pulmonary thromboendarterectomy surgery as a potential
      cure for chronic thromboembolic pulmonary hypertension. Most surgeons considered
      that this procedure should be restricted to designated expert centers, and
      acknowledged the need to organize dedicated regional meetings where clinical
      practice guidelines can be established and updated as appropriate for regional
      healthcare facilities. Conclusions Although much effort is needed before
      pulmonary thromboendarterectomy surgery becomes widely adopted in the Asia
      Pacific region, many surgeons and centers are already seeking its implementation.
      Designating expert centers, bringing together a regional working group on
      pulmonary thromboendarterectomy, and establishing clinical practice guidelines as
      appropriate for regional healthcare facilities were recommended.

PMID- 28457174
TI  - Repair of ascending aortic pseudoaneurysm eroding through the sternum.
AB  - In reoperation for an ascending aortic pseudoaneurysm eroding through the
      sternum, a left ventricular vent allows careful unhurried sternal division under
      deep hypothermic circulatory arrest. We repaired ascending aortic pseudoaneurysms
      in 2 patients who had undergone aortic valve implantation 6 and 21 months
      earlier. A minithoracotomy was made in the left 5th intercostal space, and a vent
      was placed in the left ventricular apex. Repair was accomplished with a bovine
      pericardial patch reinforced with a Teflon felt strip. Both patients made an
      uneventful recovery with good functional status at discharge at the 8- and 18
      month follow-up.

PMID- 28457175
TI  - Tissue Engineering and Regenerative Medicine: New Trends and Directions-A Year in
      Review.
AB  - Tissue engineering (TE) is continuously evolving assimilating inputs from
      adjacent scientific areas and their technological advances, including
      nanotechnology developments that have been spawning the range of available
      options for the precise manipulation and control of cells and cellular
      environments. Simultaneously, with the maturation of the field, TE has a growing
      and marked impact in other fields, such as cancer and other diseases research,
      enabling tri-dimensional (3D) tumor/tissue models of increased complexity that
      more closely resemble living tissue dynamics, playing a decisive role in the
      development of new and improved therapies. Nevertheless, TE is still struggling
      with translational issues. On this matter, the advent of personalized and
      precision medicine has opened new perspectives, particularly with the striking
      evolutions enabled by 3D bioprinting technologies. Based on a modified
      methodology grounded in the past years' approach, we have identified and reviewed
      some of the most high-impact publications on the topics that are revolutionizing
      TE and helping to define the future directions of the field, namely: (1) New
      trends in TE: Personalized/precision regenerative medicine and 3D bioprinting,
      (2) Contributions of TE to other fields: microfabricated tissue-engineered 3D
      models for cancer and other diseases research, and (3) Diagnostic and theranostic
      tools: monitoring and real-time control of TE systems.

PMID- 28457176
TI  - 3D digital subtracted CT angiography to evaluate the venous anatomy in extra
      axial tumors invading the major dural venous sinuses.
AB  - Background Investigation of the venous system surrounding a tumor that is
      invading a dural sinus is of great use for guiding the surgical excision. Non
      invasive imaging is often inadequate since enhancement of the tumor causes it to
      blend with the contrast of the venous vascular structures. Conventional two
      dimensional angiography is also often insufficient. Objective The objective of
      this study was to report regarding the potential of three-dimensional digital
      subtracted computed tomography angiography (3D DS-CTA) as a technique to
      preoperatively explore these tumors. Methods We retrospectively studied the
      radiological and surgical features of patients explored with 3D DS-CTA for a
      tumor invading a major dural sinus. Results Three patients were included in this
      study, one hemangiopericytoma and two meningiomas. 3D DS-CTA allows for accurate
      assessment of the patency of the sinus, the location of the secondary intra- and
      trans-osseous venous outlets, and surgical guidance by neuronavigation.
      Conclusion 3D DS-CTA could be a promising guiding and diagnostic tool for the pre
      and intraoperative treatment of vascular tumors invading the dural sinuses, for
      which the venous morbidity and mortality is substantial.

PMID- 28457177
TI  - High-sensitivity cardiac troponin assays: From improved analytical performance to
      enhanced risk stratification.
AB  - Implementation of cardiac troponin (cTn) assays has revolutionized the diagnosis,
      risk stratification, triage and management of patients with suspected myocardial
      infarction (MI). The Universal Definition of MI brought about a shift in the
      diagnostics of MI, from an approach primarily based on electrocardiography (ECG)
      to one primarily based on biomarkers. Currently, detection of a rise and/or fall
      in concentration or activity of myocardial necrosis biomarkers, preferentially
      cTns, with at least one value above the 99th percentile upper reference limit
      (URL), is the essential component for the diagnosis of MI. High-sensitivity
      cardiac troponin (hs-cTn) assays with their superior analytical performance were
      designed to further facilitate clinical decision making. The ability of hs-cTn
      assays to detect measurable cTn concentrations in at least 50% of healthy
      individuals, along with their improved precision (expressed as coefficient of
      variation <=10% at the 99th percentile URL) associated with increased recognition
      of changing values, leads to enhanced risk stratification of patients with
      suspected MI, and also enables them to be used as prognostic tools potentially
      useful in other patient subsets. In this comprehensive review, we aim to
      integrate updated laboratory and clinical knowledge regarding hs-cTn assays in
      order to promote their optimal use in daily practice. We primarily focus on the
      role of hs-cTn assays in patients with suspected MI, discussing recommended
      diagnostic algorithms and result interpretation. Emphasis is also placed on the
      release of cTns following myocardial injury, the characteristics of antibodies
      used in available cTn immunoassays, and analytical performance of hs-cTn assays.
      In this paper, we also review potential challenges related to the selection of a
      healthy reference population in determining 99th percentile values, biological
      variation of hs-cTns, inequality between hs-cTn assays, and outline the current
      status of cTnI standardization. Finally, we discuss in detail the diagnostic and
      prognostic value of hs-cTn assays, including non-coronary causes of cTn
      elevation, the potential benefits and risks of point-of-care testing, and the
      unjustified skepticism of some clinicians regarding implementation of hs-cTn
      assays. In everyday clinical practice, hs-cTn assays are an important diagnostic
      advance, predominantly for patients with non-ST-segment elevation acute coronary
      syndrome (NSTE-ACS), with suspected non-ST-segment elevation myocardial
      infarction (NSTEMI). In the NSTE-ACS setting, recently introduced short
      diagnostic algorithms using hs-cTn assays integrated with careful clinical and
      ECG assessment were found to substantially reduce the time to final diagnosis,
      shorten visits to the emergency department and allow earlier safe discharge of
      low risk subjects. Hs-cTn assays have significantly higher sensitivity and
      negative predictive value for NSTEMI in comparison to contemporary cTn tests,
      particularly in early NSTE-ACS presenters. However, due to frequently occurring
      mild hs-cTn elevations, they are also associated with lower specificity and
      reduced positive predictive value when compared to previous generations of
      assays. Our review underscores the need for the education of clinicians and
      medical laboratory professionals regarding appropriate use and interpretation of
      hs-cTn assays. Adequate training and clinical experience in using these tests are
      essential to translate the improved analytical performance of hs-cTn assays into
      enhanced risk stratification and hopefully better patient outcomes.

PMID- 28457178
TI  - Postoperative Outcomes in Graves' Disease Patients: Results from the Nationwide
      Inpatient Sample Database.
AB  - BACKGROUND: Current surgical indications for Graves' disease include
      intractability to medical and/or radioablative therapy, compressive symptoms, and
      worsening ophthalmopathy. Total thyroidectomy for Graves' disease may be
      technically challenging and lead to untoward perioperative outcomes. This study
      examines outcomes in patients with Graves' disease who underwent total
      thyroidectomy and assesses its safety for this patient population. METHODS: A
      retrospective cross-sectional analysis was performed using the Nationwide
      Inpatient Sample database from 2006 to 2011. Total thyroidectomy performed in
      patients with Graves' disease, benign multinodular goiter (MNG), and thyroid
      cancer was identified. Demographic factors, comorbidities, and postoperative
      complications were evaluated. Chi-square, one-way analysis of variance, and risk
      adjusted multivariable logistic regression were performed. RESULTS: Of 215,068
      patients who underwent total thyroidectomy during the study period, 11,205 (5.2%)
      had Graves' disease, 110,124 (51.2%) MNG, and 93,739 (43.6%) thyroid malignancy.
      Patients with Graves' disease were younger than MNG and thyroid cancer patients
      (Mage = 42.8 years vs. 55.5 and 51.0 years; p < 0.01). The Graves' disease group
      included a higher proportion of women (p < 0.01) and nonwhites (p < 0.01).
      Postoperatively, Graves' patients had significantly higher rates of hypocalcemia
      (12.4% vs. 7.3% and 10.3%; p < 0.01), hematomas requiring reoperation (0.7% vs.
      0.4% and 0.4%; p < 0.01), and longer mean hospital stay (2.7 days vs. 2.4 and 2.2
      days; p < 0.01) compared to MNG and thyroid cancer patients, respectively. On
      risk-adjusted multivariate logistic regression, Graves' disease was independently
      associated with a higher risk of vocal-cord paralysis (odds ratio [OR] = 1.36
      [confidence interval (CI) 1.08-1.69]), tracheostomy (OR = 1.35 [CI 1.1-1.67]),
      postoperative hypocalcemia (OR = 1.65 [CI 1.54-1.77]), and hematoma requiring
      reoperation (OR = 2.79 [CI 2.16-3.62]) compared to MNG patients. High-volume
      centers for total thyroidectomy were independently associated with lower risk of
      postoperative complications, including in patients with Graves' disease.
      CONCLUSIONS: Despite low overall morbidity following total thyroidectomy, Graves'
      disease patients are at increased risk of postoperative complications, including
      bleeding, vocal-cord paralysis, tracheostomy, and hypocalcemia. These risks
      appear to be lower when performed at high-volume centers, and thus referral to
      these centers should be considered. Total thyroidectomy may therefore be a safe
      treatment option for appropriately selected patients with Graves' disease when
      performed by experienced surgeons.

PMID- 28457180
TI  - EDC Cross-linking of Decellularized Tissue: A Promising Approach?
AB  - BACKGROUND: Decellularization of xenogenous cardiovascular structures is a
      promising approach to create scaffolds for tissue engineering. Unfortunately,
      handling and pliability of the unfixed tissue is challenging. N-(3
      dimethylaminopropyl)-N9-ethylcarbodiimide (EDC) is an alternative cross-linking
      agent to glutaraldehyde (GA). Applied in native tissue, it provides
      biocompatibility and shows no potential for calcification. In addition, EDC can
      be used to link growth factors (GFs) to tissue scaffolds after decellularization.
      EDC cross-linking could thereby help to improve decellularized tissue without the
      toxicity of GA. MATERIAL AND METHODS: Porcine aortic wall tissue specimens (TS)
      were decellularized, treated with EDC, and coated with fibroblast growth factor
      (FGF) or vascular endothelial growth factor (VEGF). Afterward, TS were
      subcutaneously implanted in 36 Lewis rats along with one decellularized TS
      without EDC treatment. After 2, 4, and 6 weeks TS were explanted from 12 rats,
      respectively. Vital cells were evaluated by RNA quantification, general cellular
      infiltration by hematoxylin and eosin staining (H&E), macrophage infiltration by
      CD68 staining, calcification by Von-Kossa staining, and tissue degradation by
      measurement of TS thickness. RESULTS: Quantification of vital cells showed
      reduced reseeding of EDC-treated TS compared to noncross-linked TS after 2 (p <
      0.05) and 4 weeks (p < 0.05), while after 6 weeks only EDC+VEGF showed fewer
      viable cells (p < 0.01). Histological evaluation confirmed a reduced infiltration
      of EDC-treated TS. Macrophage infiltration decreased in all groups from 2 to 6
      weeks, with the smallest population in EDC+VEGF-treated TS (p > 0.05). In EDC+FGF
      treated TS, macrophages were reduced after 2 weeks compared to noncross-linked TS
      (p < 0.05), while after 4 and 6 weeks no significant difference was found (p >
      0.05). Von-Kossa staining revealed no calcification in any of the specimens.
      Thickness of noncross-linked and EDC+FGF-treated TS was not different at the
      respective times of explantation, but decreased in both groups toward 6 weeks.
      CONCLUSION: EDC cross-linking combined with GF coating of decellularized aortic
      wall tissue showed encouraging results. The treatment did not impair the
      advantages of decellularized tissue such as long-term recellularization, absence
      of calcification, and tissue integrity. Based on the low macrophage infiltration
      and minimal tissue degradation, treatment with EDC and VEGF could be useful after
      decellularization. However, further research is necessary to verify these
      findings in models, including mechanical stress.

PMID- 28457179
TI  - Extracellular Matrix Bioscaffolds as Immunomodulatory Biomaterials<sup/>.
AB  - Suppression of the recipient immune response is a common component of tissue and
      organ transplantation strategies and has also been used as a method of mitigating
      the inflammatory and scar tissue response to many biomaterials. It is now
      recognized, however, that long-term functional tissue replacement not only
      benefits from an intact host immune response but also depends upon such a
      response. The present article reviews the limitations associated with the
      traditionally held view of avoiding the immune response, the ability of acellular
      biologic scaffold materials to modulate the host immune response and promote a
      functional tissue replacement outcome, and current strategies within the fields
      of tissue engineering and biomaterials to develop immune-responsive and
      immunoregulatory biomaterials.

PMID- 28457181
TI  - New AMH assay allows rapid point of care measurements of ovarian reserve.
AB  - In this study, we compare two commercial automated immunoassays used to evaluate
      serum anti-Mullerian hormone (AMH) levels as a prognostic value for ovarian
      response and pregnancy outcome in assisted reproductive technology cycles. Serum
      AMH was measured for 193 women. We performed a simultaneous measurement in serum
      AMH with the two alternative kits VIDAS(r) and Elecsys(r) AMH assay. For all
      women undergoing in vitro fertilization cycle, we collected data on their antral
      follicle count (AFC) and numbers of retrieved cumulus oocyte complexes (OC) and
      metaphase II oocytes and pregnancy outcome. The AMH values provided by VIDAS(r)
      were correlated with the values obtained with Elecsys(r) (0.977 for fresh and
      0.971 for the frozen samples). For both assays AMH exhibited a moderate positive
      correlation with AFC, OC and MII oocytes (0.612, 0.674, 0.605 for VIDAS(r) and
      0.570, 0.617, 0.530 for Elecsys(r), respectively). AMH prediction of biochemical
      and clinical pregnancy was similar. The present results suggest that the VIDAS(r)
      AMH assay is broadly comparable to the Elecsys-AMH assay in terms of technical
      performance for clinical or epidemiological use. Both automated assays performed
      in a similar way and the choice of assay can be made depending on the technical
      configuration of each laboratory.

PMID- 28457182
TI  - Comparison of the diagnostic accuracy of four smartphone-compatible blood
      pressure monitors in post-myocardial infarction patients.
AB  - Introduction Smartphone-compatible blood pressure devices may be a good
      alternative to enable self-measurement of blood pressure by patients.
      Furthermore, automatic transferral of data to the hospital allows for remote
      monitoring. To our knowledge, no study has compared four of these smartphone
      compatible blood pressure devices. Methods Patients who were followed up for
      acute myocardial infarction were asked to participate during their outpatient
      clinic visit. After five minutes of rest, six blood pressure devices were
      applied. The order was randomised. Four devices were smartphone-compatible. One
      device was an automated oscillometric device. One device was a handheld aneroid
      sphygmomanometer (reference device). All measurements were compared using a
      linear mixed model. Results A total of 43 patients (62.7 +/- 11.3 years, 79%
      male) were included. Compared to the reference device, four blood pressure
      monitors yielded a significant higher mean systolic blood pressure and four
      monitors yielded a significant higher diastolic BP. One device yielded a non
      significant lower mean systolic blood pressure and one device yielded a non
      significant higher mean diastolic blood pressure. Except for one blood pressure
      device, all mean differences were smaller than 5 mmHg. Conclusion In this study,
      average inter-device variability was shown to be statistically significant,
      however four devices remained within the predefined range of 5 mmHg for both
      systolic and diastolic blood pressures.

PMID- 28457185
TI  - Deep brain stimulation of the anterior limb of the internal capsule for treatment
      of therapy-refractory obsessive compulsive disorder (OCD): a case study
      highlighting neurocognitive and psychiatric changes.
AB  - Obsessive compulsive disorder (OCD) is an anxiety disorder characterized by
      repeated, unwanted thoughts and behaviors. Individuals with this condition often
      experience significant emotional distress secondary to their symptoms.
      Additionally, impairments in attention/concentration, processing speed, and
      executive functions are typically observed. The exact pathology of OCD remains
      unknown; consequently, it can be difficult to treat patients with severe
      symptomatology. Deep brain stimulation (DBS) may be a viable treatment option for
      individuals who do not respond to medication and/or cognitive behavioral therapy.
      The following case discusses DBS of the anterior limb of the internal capsule for
      a patient with severe, therapy-refractory OCD, including pre- to postoperative
      neurocognitive and psychiatric changes.

PMID- 28457184
TI  - Changes in Hepatic TRbeta Protein Expression, Lipogenic Gene Expression, and Long
      Chain Acylcarnitine Levels During Chronic Hyperthyroidism and Triiodothyronine
      Withdrawal in a Mouse Model.
AB  - BACKGROUND: Thyroid hormone (TH) has important roles in regulating hepatic
      metabolism. It was previously reported that most hepatic genes activated by a
      single triiodothyronine (T3) injection became desensitized after multiple
      injections, and that approximately 10% of target genes did not return to basal
      expression levels after T3 withdrawal, despite normalization of serum TH and
      thyrotropin (TSH) levels. To determine the possible mechanism(s) for
      desensitization and incomplete recovery of hepatic target gene transcription and
      their effects on metabolism, mRNA and/or protein expression levels of key
      regulators of TH action were measured, as well as metabolomic changes after
      chronic T3 treatment and withdrawal. METHODS: Adult male mice were treated with
      daily injections of T3 (20 MUg/100 g body weight) for 14 days followed by the
      cessation of T3 for 10 days. Livers were harvested at 6 hours, 24 hours, and 14
      days after the first T3 injection, and at 10 days after withdrawal, and then
      analyzed by quantitative reverse transcription polymerase chain reaction, Western
      blotting, and metabolomics. RESULTS: Although TH receptor (TRalpha and TRbeta)
      mRNAs decreased slightly after chronic T3 treatment, only TRbeta protein
      decreased before returning to basal expression level after withdrawal. The
      expression of other regulators of TH action was unchanged. TRbeta protein
      expression was also decreased in adult male monocarboxylate transporter-8 (Mct8)
      knockout mice, an in vivo model of chronic intrahepatic hyperthyroidism.
      Previously, increased hepatic long-chain acylcarnitine levels were found after
      acute TH treatment. However, in this study, long-chain acylcarnitine levels were
      unchanged after chronic T3, and paradoxically increased after T3 withdrawal.
      Pathway analyses of the previous microarray results showed upregulation of
      lipogenic genes after acute T3 treatment and withdrawal. Phosphorylation of
      acetyl-CoA carboxylase also decreased after T3 withdrawal. CONCLUSIONS: Decreased
      hepatic TRbeta protein expression occurred after chronic T3 exposure in adult
      male wild-type and Mct8-knockout mice. Gene array pathway and metabolomics
      analyses showed abnormalities in hepatic lipogenic gene expression and
      acylcarnitine levels, respectively, after withdrawal, despite normalization of
      serum TSH and TH levels. These findings may help explain the variable clinical
      presentations of some patients during hyperthyroidism and recovery, since TRbeta
      protein, target gene expression, and metabolic adaptive changes can occur in
      individual tissues without necessarily being reflected by circulating TH and TSH
      concentrations.

PMID- 28457186
TI  - Heparin Augmentation Enhances Bioactive Properties of Acellular Extracellular
      Matrix Scaffold.
AB  - Extracellular matrix (ECM) maintains a reservoir of bioactive growth factors and
      matricellular proteins that provide bioinductive effects on local cells that
      influence phenotype and behaviors. Bioactive acellular ECM scaffolds can be used
      therapeutically to stimulate adaptive tissue repair. Fibroblast growth factor-2
      (FGF-2) attenuates transforming growth factor-beta1 (TGF-beta1)-mediated cardiac
      fibrosis. Heparin glycosaminoglycan can influence FGF-2 bioactivity and could be
      leveraged to enhance tissue engineering strategies. We explored the effects of
      heparin on FGF-2 enhancement of bioactive ECM scaffold biomaterials for its
      antifibrotic effect on attenuating human cardiac myofibroblast activation.
      Increasing heparin concentration at a fixed concentration of FGF-2 markedly
      increased the amount of FGF-2 retained and eluted by ECM scaffolds. To explore
      synergistic bioinductive effects of heparin and FGF-2, collagen gel contraction
      assay using human cardiac myofibroblasts was performed in vitro. Myofibroblast
      activation was induced by profibrotic cytokine, TGF-beta1. FGF-2 and heparin in
      combination reduced human cardiac myofibroblast-mediated collagen gel contraction
      to a greater extent than FGF-2 alone. These observations were confirmed for both
      human atrial and human ventricular cardiac fibroblasts. Cell death was not
      different between groups. In summary, heparin is an effective adjuvant to enhance
      FGF-2 loading and elution of acellular ECM scaffold biomaterials. Heparin
      increases the bioactive effects of FGF-2 in attenuating human cardiac
      myofibroblast activation in response to profibrotic TGF-beta1. These data may
      inform tissue engineering strategies for myocardial repair to prevent fibrosis.

PMID- 28457187
TI  - Laser-Etched Designs for Molding Hydrogel-Based Engineered Tissues.
AB  - Rapid prototyping and fabrication of elastomeric molds for sterile culture of
      engineered tissues allow for the development of tissue geometries that can be
      tailored to different in vitro applications and customized as implantable
      scaffolds for regenerative medicine. Commercially available molds offer minimal
      capabilities for adaptation to unique conditions or applications versus those for
      which they are specifically designed. Here we describe a replica molding method
      for the design and fabrication of poly(dimethylsiloxane) (PDMS) molds from laser
      etched acrylic negative masters with ~0.2 mm resolution. Examples of the variety
      of mold shapes, sizes, and patterns obtained from laser-etched designs are
      provided. We use the patterned PDMS molds for producing and culturing engineered
      cardiac tissues with cardiomyocytes derived from human-induced pluripotent stem
      cells. We demonstrate that tight control over tissue morphology and anisotropy
      results in modulation of cell alignment and tissue-level conduction properties,
      including the appearance and elimination of reentrant arrhythmias, or circular
      electrical activation patterns. Techniques for handling engineered cardiac
      tissues during implantation in vivo in a rat model of myocardial infarction have
      been developed and are presented herein to facilitate development and adoption of
      surgical techniques for use with hydrogel-based engineered tissues. In summary,
      the method presented herein for engineered tissue mold generation is
      straightforward and low cost, enabling rapid design iteration and adaptation to a
      variety of applications in tissue engineering. Furthermore, the burden of
      equipment and expertise is low, allowing the technique to be accessible to all.

PMID- 28457189
TI  - Effects of cognitive remediation therapy versus other interventions on cognitive
      functioning in schizophrenia inpatients.
AB  - Computerised cognitive remediation therapy (CCRT) has been shown to improve
      cognitive function in individuals with schizophrenia beyond effects of other
      forms of therapy. However, results vary between studies, and most are aimed at
      individuals who are living in the community. Very few studies have investigated
      its efficacy in psychiatric wards in order to assess whether or not this is a
      suitable site to start the therapy. This study evaluated CCRT efficacy among
      schizophrenia inpatients who received a broad range of therapeutic interventions
      in a psychiatric ward. A randomised controlled trial of CCRT versus an active
      control in 66 young inpatients with a diagnosis of schizophrenia was conducted.
      The intervention lasted for 6 weeks and its efficacy was assessed with the
      composite score of the MATRICS Consensus Cognitive Battery. Both groups improved
      similarly in cognitive function and psychopathological symptoms. However, the
      CCRT group improved more than the controls in negative symptoms. This result
      shows that providing a drill and practice cognitive remediation to inpatients
      does not produce benefits for cognitive functioning substantially greater than
      other forms of therapy provided in a ward, but it is more efficient in reduction
      of negative symptoms. Our results suggest that CRT might be considered as a
      promising intervention for reducing negative symptoms in schizophrenia
      individuals.

PMID- 28457188
TI  - Functional Tissue Engineering: A Prevascularized Cardiac Muscle Construct for
      Validating Human Mesenchymal Stem Cells Engraftment Potential In Vitro.
AB  - The influence of somatic stem cells in the stimulation of mammalian cardiac
      muscle regeneration is still in its early stages, and so far, it has been
      difficult to determine the efficacy of the procedures that have been employed.
      The outstanding question remains whether stem cells derived from the bone marrow
      or some other location within or outside of the heart can populate a region of
      myocardial damage and transform into tissue-specific differentiated progenies,
      and also exhibit functional synchronization. Consequently, this necessitates the
      development of an appropriate in vitro three-dimensional (3D) model of
      cardiomyogenesis and prompts the development of a 3D cardiac muscle construct for
      tissue engineering purposes, especially using the somatic stem cell, human
      mesenchymal stem cells (hMSCs). To this end, we have created an in vitro 3D
      functional prevascularized cardiac muscle construct using embryonic cardiac
      myocytes (eCMs) and hMSCs. First, to generate the prevascularized scaffold, human
      cardiac microvascular endothelial cells (hCMVECs) and hMSCs were cocultured onto
      a 3D collagen cell carrier (CCC) for 7 days under vasculogenic culture
      conditions; hCMVECs/hMSCs underwent maturation, differentiation, and
      morphogenesis characteristic of microvessels, and formed dense vascular networks.
      Next, the eCMs and hMSCs were cocultured onto this generated prevascularized CCCs
      for further 7 or 14 days in myogenic culture conditions. Finally, the vascular
      and cardiac phenotypic inductions were characterized at the morphological,
      immunological, biochemical, molecular, and functional levels. Expression and
      functional analyses of the differentiated progenies revealed neo-cardiomyogenesis
      and neo-vasculogenesis. In this milieu, for instance, not only were hMSCs able to
      couple electromechanically with developing eCMs but were also able to contribute
      to the developing vasculature as mural cells, respectively. Hence, our unique 3D
      coculture system provides us a reproducible and quintessential in vitro 3D model
      of cardiomyogenesis and a functioning prevascularized 3D cardiac graft that can
      be utilized for personalized medicine.

PMID- 28457190
TI  - Exosome-Like Vesicles Derived from Adipose Tissue Provide Biochemical Cues for
      Adipose Tissue Regeneration.
AB  - There is an emerging need for soft tissue replacements in the field of
      reconstructive surgery for the treatment of congenital deformities, posttraumatic
      repair, and cancer rehabilitation. Previous studies have shown that the bioactive
      adipose tissue extract can induce adipogenesis without additional stem cells or
      growth factors. In this study, we innovatively investigated whether exosome-like
      vesicles derived from adipose tissue (ELV-AT) could direct stem cell
      differentiation and trigger adipose tissue regeneration. In vitro, ELV-AT can
      induce adipogenesis of adipose-derived stem cells and promote proliferation,
      migration, and angiogenic potential of the aorta endothelial cells. In vivo, ELV
      AT were transplanted to a chamber on the back of nude mice and neoadipose tissues
      were formed. Our findings indicated that ELV-AT could be used as a cell-free
      therapeutic approach for adipose tissue regeneration.

PMID- 28457191
TI  - How can we ensure value for money from expenditure on injectable cancer drugs?

PMID- 28457193
TI  - Strengthening health systems to provide rehabilitation services.

PMID- 28457192
TI  - Assessment of adherence and relative dose intensity with oral chemotherapy in
      oncology clinical trials at an academic medical center.
AB  - Background/Aims Oral chemotherapy is increasingly utilized leaving the patient
      responsible for self-administering an often complex regimen where adverse effects
      are common. Non-adherence and reduced relative dose intensity are both associated
      with poorer outcomes in the community setting but are rarely reported in clinical
      trials. The purpose of this study is to quantify adherence and relative dose
      intensity in oncology clinical trials and to determine patient and study related
      factors that influence adherence and relative dose intensity. Methods Patients
      were identified from non-industry-funded clinical trials conducted between 1
      January 2009 and 31 March 2013 at the University of Wisconsin Carbone Cancer
      Center. Data were extracted from primary research records. Descriptive statistics
      and linear regression modeling was performed using SAS 9.4. Results A total of 17
      clinical trials and 266 subjects were included. Mean adherence was greater than
      97% for the first eight cycles. Mean relative dose intensity was less than 90%
      for the first cycle and declined over time. Male gender, a performance status of
      1 or 2, metastatic disease, and traveling more than 90 miles to reach the cancer
      center were associated with higher relative dose intensity. Conclusions Patients
      with cancer enrolled in clinical trials are highly adherent but unlikely to
      achieve protocol specified relative dose intensity. Given that determining the
      phase II dose is the primary endpoint of phase I trials, incorporating relative
      dose intensity into this determination should be considered.

PMID- 28457195
TI  - Exploring patients' perceptions of accessing electronic health records:
      Innovation in healthcare.
AB  - The more widespread implementation of electronic health records has led to new
      ways of providing access to healthcare information, allowing patients to view
      their medical notes, test results, medicines and so on. In this article, we
      explore how patients perceive the possibility to access their electronic health
      record online and whether this influences patient involvement. The study includes
      interviews with nine patients and a survey answered by 56 patients. Our results
      show that patients perceive healthcare information to be more accessible and that
      electronic health record accessibility improves recall, understanding and patient
      involvement. However, to achieve the goal of involving patients as active
      decision-makers in their own treatment, electronic health records need to be
      fully available and test results, referrals and information on drug interactions
      need to be offered. As patient access to electronic health records spreads, it is
      important to gain a deeper understanding of how documentation practices can be
      changed to serve healthcare professionals and patients.

PMID- 28457194
TI  - The Best Approach for Laparoscopic Fluorescence Cholangiography: Overview of the
      Literature and Optimization of Dose and Dosing Time.
AB  - BACKGROUND: Fluorescence cholangiography using indocyanine green (ICG) can
      enhance orientation of bile duct anatomy during laparoscopic cholecystectomy. To
      ensure clear discrimination between bile ducts and liver, the fluorescence ratio
      between both should be sufficient. This ratio is influenced by the ICG dose and
      timing of fluorescence imaging. We first systematically identified all strategies
      for fluorescence cholangiography. Second, we aimed to optimize the dose of ICG
      and dosing time in a prospective clinical trial. METHODS: PubMed was searched for
      clinical trials studying fluorescence cholangiography. Furthermore, 28 patients
      planned to undergo laparoscopic cholecystectomy were divided into 7 groups,
      receiving different intravenous doses (5 or 10 mg ICG) at different time points
      (0.5, 2, 4, 6, or 24 hours prior to surgery). RESULTS: The systematic review
      revealed 27 trials including 1057 patients. The majority of studies used 2.5 mg
      administered within 1 hour before imaging. Imaging 3 to 24 hours after ICG
      administration was never studied. The clinical trial demonstrated that the
      highest bile duct-to-liver ratio was achieved 3 to 7 hours after administration
      of 5 mg and 5 to 25 hours after administration of 10 mg ICG. Up to 3 hours after
      administration of 5 mg and up to 5 hours after administration of 10 mg ICG, the
      liver was equally or more fluorescent than the cystic duct, resulting in a ratio
      <=1.0. CONCLUSION: This study shows for the first time that the interval between
      ICG administration and intraoperative fluorescence cholangiography should be
      extended. Administering 5 mg ICG at least 3 hours before imaging is easy to
      implement in everyday clinical practice and results in bile duct-to-liver ratios
      >1.0.

PMID- 28457196
TI  - Immunomodulation in systemic lupus erythematosus: induction of M2 population in
      monocyte-derived macrophages by pioglitazone.
AB  - Macrophages have recently gained attention in systemic lupus erythematosus (SLE)
      pathogenesis for their role in the anti-inflammatory clearance of apoptotic
      cells. The M1/M2 polarization of macrophages improves efferocytic capability.
      Peroxisome proliferator-activated receptor gamma is proposed to function in the
      expansion of the M2 subpopulation. Pioglitazone is a peroxisome proliferator
      activated receptor gamma agonist with a variety of anti-inflammatory effects. In
      this paper, we investigated the ex vivo alterations of monocyte-derived
      macrophages of 15 newly diagnosed SLE patients and 10 normal subjects triggered
      by apoptotic cells among SLE patients following pioglitazone treatment. The
      phagocytosis capacity of macrophages and M1/M2 polarization (CD86/CD163) was
      evaluated. The supernatants were also analyzed for the expression of interleukin
      (IL)-10, IL-12, transforming growth factor beta1 and TNF-alpha. The mRNA
      expression of IL-1beta and mannose receptor C-type 1 were also quantified among
      treated and non-treated monocyte-derived macrophages. We found that efferocytosis
      is defective among monocyte-derived macrophages of SLE patients and might be a
      major underlying mechanism involved in the sustained inflammation. Pioglitazone
      could enhance alternative activation of monocyte-derived macrophages and
      consequently immunomodulation in these patients.

PMID- 28457197
TI  - Management of cardiovascular risk in systemic lupus erythematosus: a systematic
      review.
AB  - Systemic lupus erythematosus is associated with accelerated atherosclerosis and
      increased risk of cardiovascular complications. The aim of this study was to
      review the effectiveness of interventions for primary and secondary prevention of
      cardiovascular events and mortality and to review the effectiveness of
      interventions for cardiovascular risk factor reduction in systemic lupus
      erythematosus patients. A systematic review was conducted. Electronic databases
      Medline and Embase (1961-2015) were searched. Nineteen articles met the inclusion
      criteria and were selected. Low-calorie and/or low glycaemic index calories may
      be a useful option for secondary prevention in obese patients with systemic lupus
      erythematosus, and exercise would be useful in improving the endothelial function
      measured by flow-mediated dilation in this group of patients. The use of lipid
      lowering drugs may improve the lipid profile in patients with systemic lupus
      erythematosus and hyperlipidaemia, but the effect of this treatment on overall
      cardiovascular mortality remains unknown. Antiplatelets, anticoagulants,
      antimalarials and lipid-lowering drugs may be effective in the primary and
      secondary prevention of major cardiovascular events, such as acute myocardial
      infarction or stroke. Similarly, lipid-lowering drugs and antimalarial drugs
      appear to reduce the serum levels of total cholesterol, low-density lipoprotein,
      glucose, diastolic blood pressure and calcium deposition at the coronary
      arteries. They may also improve insulin resistance and the level of high-density
      lipoproteins. It appears that treatment with antihypertensive drugs reduces blood
      pressure in patients with systemic lupus erythematosus, but the available studies
      are of low quality.

PMID- 28457198
TI  - Effectiveness of cognitive rehabilitation for people with multiple sclerosis: a
      meta-synthesis of patient perspectives.
AB  - While previous randomised controlled trials and meta-analyses offer only limited
      evidence for the effectiveness of cognitive rehabilitation, qualitative studies
      examining patient perspectives report more positive outcomes. This meta-synthesis
      of qualitative studies examined patient perspectives of cognitive rehabilitation
      for memory, attention, and executive function problems in people with multiple
      sclerosis. Using set eligibility criteria, we screened electronic databases,
      reference lists, and academic networks for relevant papers. Seven papers (195
      participants) were selected. Two independent researchers conducted quality
      appraisals of papers. Data analysis, guided by the thematic synthesis approach,
      yielded six main themes. These suggested that patients benefitted from the group
      environment in rehabilitation. Cognitive rehabilitation facilitated the
      participants' reflection and awareness of their cognitive deficits, and was
      associated with increased knowledge and understanding of their illness. Increased
      strategy use was reported and associated with improvements in cognitive
      functioning and greater confidence and perseverance. Participants reported
      emotional and social improvements, and felt more optimistic. Overall, these
      changes had a positive impact on participants' quality of life. This synthesis of
      qualitative studies indicates that people with multiple sclerosis who experience
      cognitive deficits benefit from cognitive rehabilitation programmes. This finding
      must, however, be viewed in light of the limitations of this meta-synthesis. The
      meta-synthesis was registered in the PROSPERO database under CRD42017040148.

PMID- 28457199
TI  - * Bone Regeneration Mediated by a Bioactive and Biodegradable Extracellular
      Matrix-Like Hydrogel Based on Elastin-Like Recombinamers.
AB  - The morbidity of bone fractures and defects is steadily increasing due to changes
      in the age pyramid. As such, novel biomaterials that are able to promote the
      healing and regeneration of injured bones are needed to overcome the limitations
      of auto-, allo-, and xenografts, while providing a ready-to-use product that may
      help to minimize surgical invasiveness and duration. In this regard, recombinant
      biomaterials, such as elastin-like recombinamers (ELRs), are very promising as
      their design can be tailored by genetic engineering, thus allowing scalable
      production and batch-to-batch consistency, among others. Furthermore, they can
      self-assemble into physically crosslinked hydrogels above a certain transition
      temperature, in this case body temperature, but are injectable below this
      temperature, thereby markedly reducing surgical invasiveness. In this study, we
      have developed two bioactive hydrogel-forming ELRs, one including the osteogenic
      and osteoinductive bone morphogenetic protein-2 (BMP-2) and the other the Arg-Gly
      Asp (RGD) cell adhesion motif. The combination of these two novel ELRs results in
      a BMP-2-loaded extracellular matrix-like hydrogel. Moreover, elastase-sensitive
      domains were included in both ELR molecules, thereby conferring biodegradation as
      a result of enzymatic cleavage and avoiding the need for scaffold removal after
      bone regeneration. Both ELRs and their combination showed excellent
      cytocompatibility, and the culture of cells on RGD-containing ELRs resulted in
      optimal cell adhesion. In addition, hydrogels based on a mixture of both ELRs
      were implanted in a pilot study involving a femoral bone injury model in New
      Zealand white rabbits, showing complete regeneration in six out of seven cases,
      with the other showing partial closure of the defect. Moreover, bone neoformation
      was confirmed using different techniques, such as radiography, computed
      tomography, and histology. This hydrogel system therefore displays significant
      potential in the regeneration of bone defects, promoting self-regeneration by the
      surrounding tissue with no involvement of stem cells or osteogenic factors other
      than BMP-2, which is released in a controlled manner by elastase-mediated
      cleavage from the ELR backbone.

PMID- 28457200
TI  - Simultaneous Antegrade-Retrograde Subintimal Revascularization of a
      Femoropopliteal Chronic Total Occlusion by a Reentry Device-Facilitated Puncture
      of a Retrogradely Inserted Balloon.
AB  - PURPOSE: To report a rendezvous technique for subintimal revascularization of a
      chronic total occlusion (CTO) of the superficial femoral artery (SFA). TECHNIQUE:
      This maneuver is appropriate after failure to cross a long SFA CTO via intra- and
      subintimal approaches from the ipsilateral femoral as well as retrograde
      posterior tibial artery (PTA) access sites. After predilation of the subintimal
      space from the femoral access, a reentry device was placed at the level of the
      first popliteal artery segment. A balloon was delivered via the retrograde PTA
      access and inflated at the corresponding level of the reentry device. The balloon
      was punctured with the needle of the reentry device under fluoroscopic control,
      and a 0.014-inch guidewire was placed within the punctured balloon. The balloon
      and the antegrade guidewire were retracted from the retrograde access while the
      guidewire was gently pushed from the femoral site. Conventional balloon
      angioplasty of the SFA occlusion was performed via the femoral access, followed
      by overlapping stent-graft implantation. Complete revascularization of the CTO
      was documented. CONCLUSION: In selected cases a transfemoral reentry device
      assisted puncture of a retrogradely inserted balloon within the subintimal space
      may facilitate a rendezvous and revascularization if standard techniques to cross
      long CTOs have failed.

PMID- 28457201
TI  - How are sexual health clinics in England managing men who have sex with men who
      refuse to be tested for HIV?
AB  - The aim of this study was to ascertain the existence of written policies and
      common clinical practices in sexual health clinics in England for the management
      of men who have sex with men who refuse to test for HIV. All sexual health
      clinics in England ( n = 223) were invited to complete an online questionnaire in
      August-September 2014. The questionnaire covered the four domains of clinic
      policies, management practices, training and monitoring. We assess differences by
      region. Overall, 92 clinics participated. Only three clinics reported having a
      written policy. In contrast, most reported having a common agreed practice (94%
      in London vs. 71.6% elsewhere). When encountering a refusal, 72.2% of the London
      clinics and 53.4% of the clinics from elsewhere offered a less invasive option.
      Few clinics (17.4%) provided information on home sampling kits and 74.4% informed
      about other testing options. Eighty-seven per cent of the clinics recorded the
      occurrence of refusals, but only 37.8% reviewed the collected data. Providing
      staff with training was more common in London (94.1% vs. 73.8%). Clear policies
      should be developed to guide professionals when encountering men who have sex
      with men who refuse an HIV test. Offering less invasive testing options and
      information on alternative testing options could be easily introduced into
      routine practice. Efforts should be made to review monitoring data in order to
      identify implications of test refusals and introduce improvements in management
      of refusals.

PMID- 28457202
TI  - HIV/sexually transmitted infections and intimate partner violence: Results from
      the Togo 2013-2014 Demographic and Health Survey.
AB  - Among clinic-based studies, intimate partner violence (IPV) has been shown to
      contribute to HIV/AIDS among young girls and women. Results from studies among
      the general population have been less consistent. This study evaluated the
      associations between HIV infection, any sexually transmitted infections (STIs),
      and IPV in a population-based sample of Togolese women. Data from the Togo 2013
      2014 Demographic and Health Survey were utilized for these analyses. Women aged
      15-49, who were currently married, had HIV test results, and answered the
      Domestic Violence Module were analyzed (n = 2386). Generalized linear mixed
      models adjusting for sociodemographic variables, risk behaviors, and cluster
      effect were used to estimate HIV and STI risks with experience of IPV. HIV
      prevalence was 2.8%. Prevalence of IPV was 39% among HIV-positive women and 38%
      among HIV-negative women. Significant associations between IPV and HIV infection
      were not detected. Adjusted models found significant associations between
      experience of any IPV and having had STIs (OR 2.05, 95% CI 1.25-3.35). The high
      rates of violence in this setting warrant community-based interventions that
      address abuse and gender inequity. These interventions should also discuss the
      spectrum of STIs in relation to IPV.

PMID- 28457203
TI  - Bypassing the 'rapid-clearance-in-males-buffer': A fourth mechanism to explain
      how concurrency enhances STI spread.
AB  - A number of sexually transmitted infections (STIs) persist for a considerably
      shorter period in the male urethra than the vagina. If the gap between sequential
      partnerships is longer than the duration of STI colonization in males, then this
      would protect future female partners from this STI in a setting of serial
      monogamy. If, however, males have more than one partner at a time (concurrency),
      then this would enable the STI to bypass this gap/buffer. We therefore propose
      bypassing the rapid-clearance-in-males-buffer as a fourth mechanism, whereby
      concurrency could enhance the spread of STIs.

PMID- 28457204
TI  - Assessing Cognitive Representations of Antidepressants: Development and
      Validation of the Attitudes Toward Medication-Depression Inventory.
AB  - Antidepressant drugs represent the mainstay of treatment for depression; however,
      nonadherence is a major problem. Attitudes are predictors of long-term adherence
      and drive medication use. The Attitudes Toward Medication-Depression (ATM-D)
      Inventory was developed and tested with 131 patients in primary care settings who
      reported a diagnosis of depression. Content validity was assessed by experts with
      a 94.4% agreement on item relevancy. Exploratory factor analysis showed three
      factors (course of medication treatment, identity, and control) that accounted
      for 57% of the total variance in the final 17-item scale. The instrument
      demonstrated good internal consistency reliability (alpha = .76-.84) and test
      retest reliability (alpha = .74-.83). Results support the construct validity and
      reliability of the instrument and revealed unique insights into patients'
      cognitive representations of their antidepressants. This study supported that
      patients have cognitive representations related to depression and antidepressants
      that go beyond simple concerns about the effects of the medication.

PMID- 28457205
TI  - Schizophrenia: Learning About the Other Half.

PMID- 28457206
TI  - Embracing Uncertainty as a First-Year Therapist Treating a Patient Who Has
      Obsessive-Compulsive Disorder.

PMID- 28457207
TI  - * Early and Marked Enhancement of New Bone Quality by Alendronate-Loaded Collagen
      Sponge Combined with Bone Morphogenetic Protein-2 at High Dose: A Long-Term Study
      in Calvarial Defects in a Rat Model.
AB  - Choice of appropriate biomaterial is a key factor for the success of recombinant
      human bone morphogenetic protein (rhBMP)-2 therapy. Inspired by osteogenic cell
      differentiating and osteoclast-suppressing capabilities of alendronate (ALN), we
      manufactured a composite type of ALN-loaded collagen sponge (ALN-CS), which
      controls the early detrimental effect of high-dose rhBMP-2. This study aimed to
      evaluate ALN-CS as a high-dose rhBMP-2 carrier by investigating its initial
      biomolecular effect and efficacy on intramembranous ossification at 1, 4, 8, and
      24 weeks using a rat calvarial defect model compared with nonloaded CS. The in
      vitro rhBMP-2 release in the ALN-CS showed a low initial burst and steady release
      phase during the rest period despite lack of calcium compared with that in CS
      alone. ALN release showed the same tendency as rhBMP-2 release. In vitro
      characterization showed that osteoblast differentiation and mineralization of
      mesenchymal stromal cells were more enhanced with ALN-CS. The ALN-CS-BMP group
      showed higher expression of bone-forming and -resorbing markers in vivo than the
      CS-BMP group after the first 7 days, which might be attributable to the
      relatively large amount of rhBMP-2 remaining. However, osteoclast activation in
      the ALN-CS-BMP group was significantly reduced compared with the CS-BMP group.
      Radiological and histological analyses revealed that ALN-CS-BMP promoted early
      and dense ossification at the initial defect, with 100% greater bone mass, 20%
      greater bone density, and less fatty marrow tissue than CS-BMP, which continued
      during the whole healing period. However, CS or ALN-CS alone failed to show
      complete defect closure even at the 24-week healing interval. Our results
      demonstrate that ALN-CS has remarkable advantages over CS alone in high-dose BMP
      2 delivery, with potent suppression of resorption, early and dense ossification
      at the target area with less fatty marrow formation, and continuation of bone
      quality over the long term, which highlights its great clinical potential as a
      rhBMP carrier for bone regeneration at intramembranous ossification sites.

PMID- 28457208
TI  - The Choice Project: Peer Workers Promoting Shared Decision Making at a Youth
      Mental Health Service.
AB  - OBJECTIVE: In youth mental health services, consumer participation is essential,
      but few implementation strategies exist to engage young consumers. This project
      evaluated an intervention implemented in an Australian youth mental health
      service that utilized peer workers to promote shared decision making via an
      online tool. METHODS: All new clients ages 16-25 were invited to participate in
      this nonrandomized comparative study, which used a historical comparison group
      (N=80). Intervention participants (N=149) engaged with a peer worker and used the
      online tool before and during their intake assessment. Pre- and postintake data
      were collected for both groups; measures included decisional conflict, perceived
      shared decision making, and satisfaction. A series of paired t tests, analyses of
      variance, and multiple regressions were conducted to assess differences in scores
      across intervention and comparison groups and pre- and postintake assessments.
      RESULTS: Ratings of perceived shared decision making with intake workers were
      higher in the intervention group than in the comparison group (p=.015). In both
      groups, decisional conflict scores were significantly lower after the intake
      assessment (p<.001 for both groups). Both perceived shared decision making and
      lower decisional conflict were associated with satisfaction (p<.015).
      CONCLUSIONS: Young people who participated in an intervention that combined peer
      work and shared decision making reported feeling more involved in their
      assessment. Feeling involved and having lower decisional conflict after seeing an
      intake worker were important for client satisfaction. These findings demonstrate
      the importance of both peer work and shared decision making for promoting optimal
      outcomes in youth mental health services.

PMID- 28457209
TI  - Patients' Experiences of Restrictive Interventions in Australia: Findings From
      the 2010 Australian Survey of Psychosis.
AB  - OBJECTIVE: The authors used survey data to investigate patients' experiences of
      restrictive interventions in inpatient settings. METHODS: The 2010 Australian
      Survey of High Impact Psychosis (N=1,825) asked about restrictive interventions
      experienced during a mental health admission in the previous year (N=428),
      ranging from restrictions on leaving a ward to seclusion. The authors explored
      the relationship between perceived benefit (good or limited versus no benefit)
      and the number of different types of restrictive interventions experienced.
      RESULTS: Twenty-three percent had recently experienced one or more restrictive
      interventions; of these, 42% had experienced forced medication and 35% had
      experienced seclusion. Although most reported some benefit, perceptions of
      benefit were lower among those who experienced a greater number of interventions.
      CONCLUSIONS: People with psychosis who experienced a greater number of
      restrictive interventions were less likely to find restrictions justified or
      beneficial. The cumulative effect of increased numbers of restrictions may also
      lead to worsening perceptions of benefit.

PMID- 28457210
TI  - Availability of Network Psychiatrists Among the Largest Health Insurance Carriers
      in Washington, D.C.
AB  - OBJECTIVE: Lack of access to mental health treatment remains a significant
      problem in the United States, even after implementation of mental health parity
      legislation. This study examined availability of psychiatrists listed in
      insurance carrier network provider databases in the Washington, D.C., area.
      METHODS: Contact information was obtained for 1,184 psychiatrists listed in
      online directories for three of the largest insurance carriers serving the
      Washington, D.C., area. The "mystery shopper" method was used to assess the
      accuracy of listed contact information, new outpatient appointment availability,
      and average wait times for 50 psychiatrists randomly selected from each insurance
      directory. RESULTS: Most (77%) physicians were successfully contacted, meaning
      that someone answered the phone or returned a voice mail message, and 51% of the
      psychiatrists had working telephone numbers verified to be correct. Fifteen
      percent of the psychiatrists were accepting new outpatients with the target
      insurance, with average wait times of 19 days; only 7% were able to schedule an
      appointment within two weeks. CONCLUSIONS: Inaccuracy of insurance provider
      directories significantly affected the ability of patients to obtain timely
      mental care.

PMID- 28457211
TI  - Expedited Medicaid Enrollment, Service Use, and Recidivism at 36 Months Among
      Released Prisoners With Severe Mental Illness.
AB  - OBJECTIVE: This study examined long-term outcomes (at 36 months) from Washington
      State's policy of expediting Medicaid enrollment for prison releasees with severe
      mental illness and compares them with previously reported short-term outcomes (at
      12 months). METHODS: Linked administrative data on prison releasees (2006-2007)
      were analyzed by using a quasi-experimental design comparing those referred to
      expedited Medicaid (N=895) with a control group of those not referred (N=2,189).
      Aggregate outcomes were analyzed with inverse probability of treatment-weighted
      logit models. RESULTS: Expedited Medicaid had a sustained effect on both
      increased months of enrollment (p<.01) and increased use of community mental
      health and general medical services (p<.01) 36 months after prison release.
      However, expedited Medicaid did not reduce criminal recidivism, consistent with
      12-month findings, Conclusions: Outcome results at 12 months were sustained at 36
      months-namely, expedited Medicaid for released prisoners with severe mental
      illness improved enrollment and service use with no effects on criminal
      recidivism.

PMID- 28457212
TI  - Implementing a Community Model of Mental Health Care in Chile: Impact on
      Psychiatric Emergency Visits.
AB  - OBJECTIVE: The community model of mental health care (CMMHC) is recommended as
      the best way to organize mental health care, but evidence of its successful
      implementation and effectiveness is scarce, particularly in resource-poor
      settings. This study aimed to evaluate the impact of CMMHC on the rate of
      psychiatric emergency visits in Santiago, Chile. METHODS: The rate of psychiatric
      emergency visits from 2006 to 2011 was compared between two health care
      administrative districts: district 1 (D1), in which CMMHC was being
      systematically implemented, and D2, where CMMHC implementation was very limited
      and inconsistent. In addition, rates of psychiatric emergency visits in ten D1
      municipalities were compared by the degree to which they had implemented CMMHC.
      RESULTS: Compared with D2, D1 had higher rates of psychiatric emergency visits
      during the observation period. In D1, the rate of visits per 100,000 inhabitants
      declined from 541 in 2006 to 414 in 2011. In D2, the rate increased from 104 in
      2006 to 130 in 2011. In D1 municipalities, the reduction in the rate of
      psychiatric emergency visits was greater in those with well-implemented CMMHC
      compared with those with partially implemented CMMHC. When distance to the
      emergency room was taken into account, the 2011 rate of emergency visits in the
      ten D1 municipalities was 21% (p<.01) lower in those with well-implemented CMMHC
      than in those with partially implemented CMMHC. CONCLUSIONS: CMMHC implementation
      leads to reduction in psychiatric emergency visits, which are burdensome to both
      users and providers. Results support CMMHC implementation in resource-poor
      settings.

PMID- 28457213
TI  - Comorbid Chronic General Health Conditions and Depression Care: A Population
      Based Analysis.
AB  - OBJECTIVE: Untreated depression among persons with chronic general health
      conditions (chronic health conditions) affects mortality, functional disability,
      quality of life, and health care costs. Currently, studies of the association
      between depression care and chronic health conditions report inconsistent
      results, and studies of depression care among persons with specific health
      conditions are rare. This study investigated the association between chronic
      health conditions and the likelihood of receiving depression care among
      individuals with depression. METHODS: Retrospective data from physician claims,
      hospital separations, vital statistics, and insurance plan registries were used
      to identify a cohort of individuals with depression and track 12-month use of
      health services among those with and without a chronic health condition.
      Disparities were analyzed by using generalized linear models. RESULTS:
      Individuals with depression and a chronic health condition had higher use of
      psychological therapy, higher use of any depression care, greater continuity of
      care, and better adherence to antidepressant therapy compared with individuals
      with depression only. However, they were less likely, in general, to be on
      antidepressant therapy, and individuals with diabetes had fewer visits to general
      practitioners for a mental health-related reason compared with individuals
      without diabetes. A trend toward lower use of any depression care was observed
      among patients with cerebrovascular disease. CONCLUSIONS: Use of depression care
      was generally higher among individuals with chronic health conditions, although
      there were differences in patterns of use by type of health condition. Some
      patients with specific health conditions could be at risk of being
      inappropriately treated for depression.

PMID- 28457214
TI  - Costs to Community Mental Health Agencies to Sustain an Evidence-Based Practice.
AB  - OBJECTIVE: Dissemination of evidence-based practices (EBPs) has become a priority
      in children's mental health services. Although implementation approaches and
      initiatives are proliferating, little is known about sustainment of EBPs, but
      evidence suggests that most EBPs are not sustained for more than a few years.
      Cost is the most frequently cited barrier to sustainment, yet very little is
      known about these costs. This study provides a method for quantifying incremental
      costs of an EBP compared with usual care and preliminary data on the costs in
      staff time, lost revenue, and other expenses of sustaining an EBP (trauma-focused
      cognitive-behavioral therapy [TF-CBT]) in community mental health settings.
      METHODS: Fourteen community mental health agencies (CMHAs) completed a measure
      developed for this study to collect administrative data on implementation costs
      to sustain TF-CBT. Survey items captured activities that were related
      specifically to TF-CBT and that would not otherwise be conducted for usual care,
      such as TF-CBT training. Staff time in hours was converted to monetary estimates.
      RESULTS: Costs varied widely across agencies. Preliminary results indicated that
      agencies spent on average $65,192 per year (2014 U.S.$) on incremental costs for
      TF-CBT sustainment (excluding costs of external trainers and other support); the
      average incremental cost per client was $1,896. CONCLUSIONS: The costs to sustain
      the EBP suggest that maintaining an EBP is a financial burden for CMHAs and that
      these costs can be a potential barrier to broader EBP uptake. Implications for
      public policy include providing reimbursement rates and financial incentives to
      offset potential implementation costs and promote sustainment of EBPs.

PMID- 28457216
TI  - A New Technique for Percutaneous Tracheotomy.
AB  - The objective of this study was to investigate a new technique for tracheal
      puncture during percutaneous dilatational tracheotomy (PDT). A new invention,
      known as SafeTrach, was used: this instrument allows exact localization of the
      puncture site with built-in protection of the posterior tracheal wall. Surgery
      was performed on 17 patients with this technique, and our experience is described
      in this report. The results showed that this new technique minimizes known risk
      factors compared with existing PDT techniques, including patients with
      disadvantageous anatomy.

PMID- 28457217
TI  - The Role of Fetuin-A and Electrolytes in the Etiology of Sialolithiasis.
AB  - Objective The aim of this study was to investigate serum and saliva fetuin-A,
      protein, and electrolyte levels in patients with sialolithiasis. Study Design
      Prospective randomized controlled study. Setting Tertiary center. Subjects and
      Methods Twenty patients with recurrent sialadenitis secondary to submandibular
      salivary gland stones and 20 asymptomatic healthy volunteers without salivary
      gland stones were included in the study. Bimanual palpation and ultrasonography
      were performed in the patient and control groups. The electrolyte, protein, and
      fetuin-A levels of the serum and saliva were measured. Results The serum calcium,
      phosphorus, and potassium levels of the patients were significantly lower than
      those of the control group (respectively, P = .04, P = .01, P = .04). There was
      no statistically significant difference between the serum fetuin-A levels of the
      2 groups ( P = .06). The saliva phosphorus values of the patients were higher
      than those of the control group ( P = .05), as were their saliva fetuin-A and
      total protein values ( P = .001, P = .01). A positive correlation was determined
      between the saliva fetuin-A levels and the saliva phosphorus and potassium levels
      of the patients ( P = .04, P = .02). The magnesium level, which has been argued
      to be a factor in the prevention of calcification, showed an increased
      correlation with the total protein in the patient group ( P = .02). Conclusion It
      is possible that the high levels of saliva fetuin-A, total protein, and
      phosphorus with insufficient of saliva magnesium levels may make a contribution
      to the formation of sialoliths.

PMID- 28457218
TI  - A 10-Year Analysis of Head and Neck Injuries Involving Nonpowder Firearms.
AB  - Objectives Firearms have an enduring and visible presence within American
      culture. However, the public health impact of nonpowder firearms and other "toy"
      guns has not been fully studied. These guns-including BB guns (ie, ball bearing),
      paintball guns, and pellet guns-are typically marketed to a younger audience. The
      objective of this study is to analyze head and neck injuries related to nonpowder
      firearms. Study Design Cross-sectional analysis of a national database. Setting
      Academic medical center. Subjects and Methods The National Electronic Injury
      Surveillance System was queried for head and neck injuries involving nonpowder
      guns, including air, BB, and pellet guns, and associated ammunition. Analysis of
      age, sex, incidence, injury location, and diagnosis was performed. Results From
      2005 to 2014, there were 1695 cases recorded, or 55,060 estimated emergency room
      visits, due to injuries related to nonpowder guns and fired ammunition. The
      majority of patients were male (80.9%). These injuries were most common in
      children 6 to 12 years of age (37.9%), followed by those 13 to 18 years old
      (27.1%) and adults (>=19 years old; 17.8%), while preschool children (0-5 years)
      represented 17.2%. The most common injury diagnosis was penetrating foreign body
      (34.9%), followed by lacerations (24.3%) and contusions/abrasions (13.7%).
      Conclusion Nonpowder and other nonlethal firearm-related injuries to the head and
      neck region are a frequent source of emergency room visits nationally. Safety
      measures and public education on a mainstream level are required.

PMID- 28457219
TI  - Commentary on Menapace et al, "Idiopathic Subglottic Stenosis: Long-Term Outcomes
      of Open Surgical Techniques".

PMID- 28457220
TI  - Response to: "Regarding 'Optimizing Positioning for In-Office Otology
      Procedures'".

PMID- 28457221
TI  - Regarding "Optimizing Positioning for In-Office Otology Procedures".

PMID- 28457222
TI  - Highlights from the Current Issue: May 2017.

PMID- 28457223
TI  - PepsinA as a Marker of Laryngopharyngeal Reflux Detected in Chronic
      Rhinosinusitis Patients.
AB  - Objectives We aimed to confirm the presence of pepsinA in the nasal secretions
      and tissues of chronic rhinosinusitis (CRS) patients and reveal the relationship
      between CRS and laryngopharyngeal reflux (LPR). Study Design Cross-sectional
      study. Setting The study was conducted at the Department of Oto-Rhino
      Laryngology, West China Hospital, Sichuan University. Subjects and Methods A
      total of 32 CRS patients with or without nasal polyps (CRSwNP and CRSsNP,
      respectively) and 10 normal controls were enrolled in our study. We investigated
      the expression of pepsinA in the nasal tissues, secretions, and blood plasma from
      the subjects by immunohistochemical staining, Western blot, or ELISA.
      Additionally, the expressions of MUC4, MUC5AC, MUC5B, MUC8, and pepsinogenA in
      nasal tissue were evaluated by quantitative real-time polymerase chain reaction.
      Results Immunohistochemistry and Western blot revealed that the pepsinA
      expression levels in the turbinate mucosa in CRSwNP/CRSsNP patients, which were
      largely restricted to the epithelial layer or glandular mucous cells in nasal
      tissues, were significantly higher than those in controls and in the polyp
      tissues of CRSwNP patients ( P < .05). In addition, the concentration of pepsinA
      in nasal secretions was significantly increased in the CRSwNP (147.85 +/- 53.69
      ng/mL, P < .001) and CRSsNP (134.12 +/- 36.23 ng/mL, P < .001) groups as compared
      with the controls (68.69 +/- 19.28 ng/mL). Although MUC5AC, MUC5B, and MUC8
      expression differed among the groups, no correlation between pepsinA and mucin
      genes was found. Conclusion The results of this study provided evidence of an
      association between LPR and CRS, although no correlation was found to exist
      between LPR and mucin genes in CRS patients.

PMID- 28457224
TI  - Accuracy of Ultrasonography and Computed Tomography in the Evaluation of Patients
      Undergoing Sialendoscopy for Sialolithiasis.
AB  - Objective To determine the accuracy of the 2 most utilized imaging modalities in
      obstructive sialadenitis secondary to sialolithiasis-computed tomography (CT) and
      ultrasonography (US)-using sialendoscopic findings as a comparison standard. To
      review the impact of CT and US on the management of sialolithiasis managed with
      sialendoscopy alone and through combined approaches. Study Design Retrospective
      cohort study. Setting Quaternary academic referral center. Subjects and Methods
      All cases of patients undergoing sialendoscopy by a single surgeon for suspected
      parotid and submandibular gland pathology between the October 2013 and April 2016
      were reviewed. Results Sixty-eight patients were in this cohort, of whom 44
      underwent US, CT, and sialendoscopy; 20 underwent CT and sialendoscopy only; and
      4 underwent US and sialendoscopy only. The sensitivity and specificity were 65%
      and 80% for US and 98% and 88% for CT, respectively. These 68 patients had 84
      total stones addressed, with 79 being removed and 5 remaining in situ. The
      methods of stone removal were sialendoscopy alone (34 stones), open transoral
      approaches (36 stones), and an external approach: transcervical for submandibular
      and transfacial for parotid (11 stones). Conclusion US had a lower sensitivity
      (65%) than what has been reported in the literature (70%-94%), and the majority
      of missed stones were anterior Wharton's duct stones. These sialoliths were
      likely missed due to an incomplete examination. US and CT were complementary in
      this study, and the findings suggest that both modalities can be utilized to
      optimize the outcome of sialendoscopy and combined approaches.

PMID- 28457225
TI  - Otoacoustic Emissions in Rural Nicaragua: Cost Analysis and Implications for
      Newborn Hearing Screening.
AB  - Objective (1) Determine the incidence and risk factors for congenital hearing
      loss. (2) Perform cost analysis of screening programs. Study Design
      Proportionally distributed cross-sectional survey. Setting Jinotega, Nicaragua.
      Subjects and Methods Otoacoustic emissions (OAEs) were used to screen 640 infants
      <6 months of age from neonatal intensive care unit, institutional, and home birth
      settings. Data on 15 risk factors were analyzed. Cost of 4 implementation
      strategies was studied: universal screening, screening at the regional health
      center (RHC), targeted screening, and screening at the RHC plus targeted
      screening. Cost-effectiveness analysis over 10 years was based on disability
      adjusted life year estimates, with the World Health Organization standard of cost
      effectiveness ratio (CER) / gross domestic product (GDP) <3, with GDP set at
      $4884.15. Results Thirty-eight infants failed the initial OAE (5.94%). In terms
      of births, 325 (50.8%) were in the RHC, 69 (10.8%) in the neonatal intensive care
      unit, and 29 (4.5%) at home. Family history and birth defect were significant in
      univariate analysis; birth defect was significant in multivariate analysis. Cost
      effectiveness analysis demonstrated that OAE screening is cost-effective without
      treatment (CER/GDP = 0.06-2.00) and with treatment (CER/GDP = 0.58-2.52).
      Conclusions Our rate of OAE failures was comparable to those of developed
      countries and lower than hearing loss rates noted among Nicaraguan
      schoolchildren, suggesting acquired or progressive etiology in the latter. Birth
      defects and familial hearing loss correlated with OAE failure. OAE screening of
      infants is feasible and cost-effective in rural Nicaragua, although highly
      influenced by estimated hearing loss severity in identified infants and the high
      travel costs incurred in a targeted screening strategy.

PMID- 28457226
TI  - Commentary: restarting NTD programme activities after the Ebola outbreak in
      Liberia.
AB  - It is widely known that the recent Ebola Virus Disease (EVD) in West Africa
      caused a serious disruption to the national health system, with many of ongoing
      disease focused programmes, such as mass drug administration (MDA) for
      onchocerciasis (ONC), lymphatic filariasis (LF) and schistosomiasis (SCH), being
      suspended or scaled-down. As these MDA programmes attempt to restart post-EVD it
      is important to understand the challenges that may be encountered. This
      commentary addresses the opinions of the major health sectors involved, as well
      as those of community members, regarding logistic needs and challenges faced as
      these important public health programmes consider restarting. There appears to be
      a strong desire by the communities to resume NTD programme activities, although
      it is clear that some important challenges remain, the most prominent being those
      resulting from the severe loss of trained staff.

PMID- 28457227
TI  - NIH workshop report on the trans-agency blood-brain interface workshop 2016:
      exploring key challenges and opportunities associated with the blood, brain and
      their interface.
AB  - A trans-agency workshop on the blood-brain interface (BBI), sponsored by the
      National Heart, Lung and Blood Institute, the National Cancer Institute and the
      Combat Casualty Care Research Program at the Department of Defense, was conducted
      in Bethesda MD on June 7-8, 2016. The workshop was structured into four sessions:
      (1) blood sciences; (2) exosome therapeutics; (3) next generation in vitro blood
      brain barrier (BBB) models; and (4) BBB delivery and targeting. The first day of
      the workshop focused on the physiology of the blood and neuro-vascular unit,
      blood or biofluid-based molecular markers, extracellular vesicles associated with
      brain injury, and how these entities can be employed to better evaluate injury
      states and/or deliver therapeutics. The second day of the workshop focused on
      technical advances in in vitro models, BBB manipulations and nanoparticle-based
      drug carrier designs, with the goal of improving drug delivery to the central
      nervous system. The presentations and discussions underscored the role of the BBI
      in brain injury, as well as the role of the BBB as both a limiting factor and a
      potential conduit for drug delivery to the brain. At the conclusion of the
      meeting, the participants discussed challenges and opportunities confronting BBI
      translational researchers. In particular, the participants recommended using BBI
      translational research to stimulate advances in diagnostics, as well as targeted
      delivery approaches for detection and therapy of both brain injury and disease.

PMID- 28457229
TI  - Correlation between therapy and lipid profile of leprosy patients: is there a
      higher risk for developing cardiovascular diseases after treatment?
AB  - BACKGROUND: The impact of leprosy reduces health-related quality of life of
      affected patients, interfering with different factors such as nutrition. This
      study investigated the lipid profile, nutritional status, and risk for
      cardiovascular disease (CVD) in patients who underwent leprosy treatment in
      Brazil. METHODS: Eighty-four adult patients of both genders ranging in age from
      20 to 60 years and diagnosed with paucibacillary (PB) or multibacillary (MB)
      leprosy were selected after undergoing multidrug treatment. The following data
      were collected: sociodemographic and clinical data; food intake; anthropometric
      measures (weight, height, and waist circumference); and lipid profile components
      (total cholesterol, high-density lipoprotein cholesterol [HDL-c], low-density
      lipoprotein cholesterol [LDL-c], and triglycerides). RESULTS: Among the study
      population, there was a predominance of males (65.48%) aged 50 to 60 years,
      patients with an income of 248-496 American dollars (63.10%), patients who
      completed elementary school (65.48%), inactive patients (76.19%), non-smokers
      (46.43%), and non-drinking patients (69.05%). The levels (mean +/- standard
      deviation) of total cholesterol were 193.8 +/- 29.4 mg/dL in the PB form and
      203.5 +/- 41.7 mg/dL in the MB form. The mean LDL-c was 116.9 +/- 22.7 mg/dL in
      PB patients and 121 +/- 31.3 mg/dL in MB patients. Mean triglyceride levels were
      123.4 +/- 45.2 mg/dL in the PB form and 147.4 +/- 88.9 mg/dL in the MB form. The
      evaluation of nutritional status showed that 41.67% of the patients were
      eutrophic, while 55.96% had excess weight. Food intake was significantly
      associated with HDL-c in male patients (P = 0.0264) and with triglycerides in
      patients above the ideal weight (P = 0.0049). CONCLUSIONS: The risk of acquiring
      CVDs was observed to be high due to patients' excess weight and increased waist
      circumference. This study will guide clinicians in the adequate treatment of
      patients with leprosy in order to avoid adverse cardiovascular events.

PMID- 28457228
TI  - Differences in gut microbial composition correlate with regional brain volumes in
      irritable bowel syndrome.
AB  - BACKGROUND: Preclinical and clinical evidence supports the concept of
      bidirectional brain-gut microbiome interactions. We aimed to determine if
      subgroups of irritable bowel syndrome (IBS) subjects can be identified based on
      differences in gut microbial composition, and if there are correlations between
      gut microbial measures and structural brain signatures in IBS. METHODS:
      Behavioral measures, stool samples, and structural brain images were collected
      from 29 adult IBS and 23 healthy control subjects (HCs). 16S ribosomal RNA (rRNA)
      gene sequencing was used to profile stool microbial communities, and various
      multivariate analysis approaches were used to quantitate microbial composition,
      abundance, and diversity. The metagenomic content of samples was inferred from
      16S rRNA gene sequence data using Phylogenetic Investigation of Communities by
      Reconstruction of Unobserved States (PICRUSt). T1-weighted brain images were
      acquired on a Siemens Allegra 3T scanner, and morphological measures were
      computed for 165 brain regions. RESULTS: Using unweighted Unifrac distances with
      hierarchical clustering on microbial data, samples were clustered into two IBS
      subgroups within the IBS population (IBS1 (n = 13) and HC-like IBS (n = 16)) and
      HCs (n = 23) (AUROC = 0.96, sensitivity 0.95, specificity 0.67). A Random Forest
      classifier provided further support for the differentiation of IBS1 and HC
      groups. Microbes belonging to the genera Faecalibacterium, Blautia, and
      Bacteroides contributed to this subclassification. Clinical features
      distinguishing the groups included a history of early life trauma and duration of
      symptoms (greater in IBS1), but not self-reported bowel habits, anxiety,
      depression, or medication use. Gut microbial composition correlated with
      structural measures of brain regions including sensory- and salience-related
      regions, and with a history of early life trauma. CONCLUSIONS: The results
      confirm previous reports of gut microbiome-based IBS subgroups and identify for
      the first time brain structural alterations associated with these subgroups. They
      provide preliminary evidence for the involvement of specific microbes and their
      predicted metabolites in these correlations.

PMID- 28457230
TI  - Effect of temperature on the Bulinus globosus - Schistosoma haematobium system.
AB  - BACKGROUND: Given that increase in temperature may alter host-parasite
      relationships, the anticipated rise in temperature due to global warming might
      change transmission patterns of certain diseases. However, the extent to which
      this will happen is not well understood. METHODS: Using a host-parasite system
      involving Bulinus globosus and Schistosoma haematobium, we assessed the effect of
      temperature on snail fecundity, growth, survival and parasite development under
      laboratory conditions. RESULTS: Our results show that temperature may have a non
      linear effect on snail fecundity and snail growth. Snails maintained at 15.5 
      degrees C and 36.0  degrees C did not produce egg masses while those maintained
      at 25.8  degrees C laid 344 and 105 more egg masses than snails at 31.0  degrees
      C and 21.2  degrees C, respectively. Attainment of patency led to a reduction in
      egg mass production among the snails. However, the reduction in fecundity for
      snails maintained at 21.2  degrees C occurred before snails started shedding
      cercariae. Parasite development was accelerated at high temperatures with snails
      maintained at 31.0  degrees C reaching patency after three weeks. Furthermore,
      snail growth rate was highest at 25.8  degrees C while it was inhibited at 15.5 
      degrees C and reduced at 31.0  degrees C. Increase in temperature increased snail
      mortality rates. Snails maintained at 36.0  degrees C had the shortest survival
      time while those maintained at 15.5  degrees C had the longest survival time.
      CONCLUSIONS: We concluded that temperature influences fecunxdity, growth,
      survival and parasite development in the snail and thus dictates the time it
      takes the parasite to complete the life cycle. This has implications on
      transmission of schistosomiasis in the context of global warming.

PMID- 28457233
TI  - Introduction to the Congenital Heart Defects: Anatomy of the Conduction System.
AB  - The position and course of the conduction system in congenital heart disease are
      intricately tied to the underlying congenital malformation. Although only subtle
      differences exist between the anatomy of the conduction axis for simple
      congenital heart lesions and normal anatomy, almost every patient with congenital
      heart disease harbors some important anatomic variation. This article summarizes
      the body of literature by retaining original classical concepts and by attempting
      to translate the available knowledge into useful points for the congenital heart
      disease specialist. This discussion spans the entire spectrum of simple to
      complex congenital heart disease.

PMID- 28457234
TI  - Bradyarrhythmias in Congenital Heart Disease.
AB  - Bradyarrhythmias in adults with congenital heart disease (CHD) comprise a complex
      group of arrhythmia disorders with congenital and acquired origins, highly
      variable long-term sequelae, and complicated treatment options. They can develop
      across the spectrum of CHD defects and can be encountered at all ages. Although
      permanent pacing is effective in treating bradyarrhythmias, it is associated with
      many complications and morbidity, where it is often used early in life. This
      section discusses the incidence and prevalence of bradyarrhythmias in the CHD
      population, their timing of occurrence with respect to specific disease entities
      and interventions, and their short- and long-term clinical sequelae.

PMID- 28457232
TI  - The evolution of CHROMOMETHYLASES and gene body DNA methylation in plants.
AB  - BACKGROUND: The evolution of gene body methylation (gbM), its origins, and its
      functional consequences are poorly understood. By pairing the largest collection
      of transcriptomes (>1000) and methylomes (77) across Viridiplantae, we provide
      novel insights into the evolution of gbM and its relationship to CHROMOMETHYLASE
      (CMT) proteins. RESULTS: CMTs are evolutionary conserved DNA methyltransferases
      in Viridiplantae. Duplication events gave rise to what are now referred to as
      CMT1, 2 and 3. Independent losses of CMT1, 2, and 3 in eudicots, CMT2 and ZMET in
      monocots and monocots/commelinids, variation in copy number, and non-neutral
      evolution suggests overlapping or fluid functional evolution of this gene family.
      DNA methylation within genes is widespread and is found in all major taxonomic
      groups of Viridiplantae investigated. Genes enriched with methylated CGs (mCG)
      were also identified in species sister to angiosperms. The proportion of genes
      and DNA methylation patterns associated with gbM are restricted to angiosperms
      with a functional CMT3 or ortholog. However, mCG-enriched genes in the gymnosperm
      Pinus taeda shared some similarities with gbM genes in Amborella trichopoda.
      Additionally, gymnosperms and ferns share a CMT homolog closely related to CMT2
      and 3. Hence, the dependency of gbM on a CMT most likely extends to all
      angiosperms and possibly gymnosperms and ferns. CONCLUSIONS: The resulting gene
      family phylogeny of CMT transcripts from the most diverse sampling of plants to
      date redefines our understanding of CMT evolution and its evolutionary
      consequences on DNA methylation. Future, functional tests of homologous and
      paralogous CMTs will uncover novel roles and consequences to the epigenome.

PMID- 28457235
TI  - Supraventricular Tachycardia in Adult Congenital Heart Disease: Mechanisms,
      Diagnosis, and Clinical Aspects.
AB  - Supraventricular arrhythmias represent a major source of morbidity in adults with
      congenital heart disease (ACHD). Anatomic variants and post-operative changes
      contribute to a unique electrophysiologic milieu ripe for the development of
      supraventricular tachycardia. Intra-atrial reentrant tachycardia is the most
      prevalent mechanism. Atrioventricular reciprocating tachycardia is common in
      lesions associated with accessory pathways. Abnormal anatomy complicates the
      management of atrioventricular nodal reentrant tachycardia. Tachycardia mediated
      by twin atrioventricular nodes is rare. Focal tachycardias are considerations in
      the ACHD population. Each of these tachycardia mechanisms is reviewed, focusing
      on the inherent diagnostic and therapeutic challenges.

PMID- 28457231
TI  - Disease management in the treatment of patients with chronic heart failure who
      have universal access to health care: a randomized controlled trial.
AB  - BACKGROUND: The efficacy of disease management programs in improving the outcome
      of heart failure patients remains uncertain and may vary across health systems.
      This study explores whether a countrywide disease management program is superior
      to usual care in reducing adverse health outcomes and improving well-being among
      community-dwelling adult patients with moderate-to-severe chronic heart failure
      who have universal access to advanced health-care services and technologies.
      METHODS: In this multicenter open-label trial, 1,360 patients recruited after
      hospitalization for heart failure exacerbation (38%) or from the community (62%)
      were randomly assigned to either disease management or usual care. Disease
      management, delivered by multi-disciplinary teams, included coordination of care,
      patient education, monitoring disease symptoms and patient adherence to
      medication regimen, titration of drug therapy, and home tele-monitoring of body
      weight, blood pressure and heart rate. Patients assigned to usual care were
      treated by primary care practitioners and consultant cardiologists. The primary
      composite endpoint was the time elapsed till first hospital admission for heart
      failure exacerbation or death from any cause. Secondary endpoints included the
      number of all hospital admissions, health-related quality of life and depression
      during follow-up. Intention-to-treat comparisons between treatments were adjusted
      for baseline patient data and study center. RESULTS: During the follow-up, 388
      (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual
      care had a primary endpoint event. The median (range) time elapsed until the
      primary endpoint event or end of study was 2.0 (0-5.0) years among patients
      assigned to disease management, and 1.8 (0-5.0) years among patients assigned to
      usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to
      1.047). Hospital admissions were mostly (70%) unrelated to heart failure.
      Patients assigned to disease management had a better health-related quality of
      life and a lower depression score during follow-up. CONCLUSIONS: This
      comprehensive disease management intervention was not superior to usual care with
      respect to the primary composite endpoint, but it improved health-related quality
      of life and depression. A disease-centered approach may not suffice to make a
      significant impact on hospital admissions and mortality in patients with chronic
      heart failure who have universal access to health care. CLINICAL TRIAL
      REGISTRATION: Clinicaltrials.gov identifier: NCT00533013 . Trial registration
      date: 9 August 2007. Initial protocol release date: 20 September 2007.

PMID- 28457236
TI  - Ventricular Arrhythmias in Adult Congenital Heart Disease: Mechanisms, Diagnosis,
      and Clinical Aspects.
AB  - The risk of ventricular arrhythmias in the adult congenital heart disease
      population increases with age. The mechanism, type, and frequency vary depending
      on the complexity of the defect, whether it has been repaired, and the type and
      timing of repair. Risk stratification for sudden death in patients with
      congenital heart disease is often challenging. Current recommendations provide a
      useful guide for management of these patients and risk stratification continues
      to evolve. Internal cardiac defibrillator implantation is often challenging due
      to limited transvenous access, often resulting in the need for epicardial or
      subcutaneous devices.

PMID- 28457237
TI  - Sudden Cardiac Death in Adult Congenital Heart Disease.
AB  - Sudden death of presumed arrhythmic etiology is a leading cause of mortality in
      adults with congenital heart disease. Anticipated benefits of the implantable
      cardioverter-defibrillator (ICD) must be weighed against high complication rates.
      Without robust evidence from randomized trials, caregivers face difficult
      decisions in selecting appropriate candidates. Although secondary prevention
      indications are often clear-cut, risk stratification for primary prevention ICDs
      is more challenging. Factors associated with sudden death in patients with
      tetralogy of Fallot are reasonably consistent across studies. In contrast,
      identification of high-risk patients with systemic right ventricles or
      univentricular hearts remains controversial.

PMID- 28457238
TI  - Arrhythmias in Patients with Atrial Defects.
AB  - Atrial arrhythmias are common in patients with atrial septal defects. A myriad of
      factors are responsible for these that include remodeling related to the defect
      and scar created by the repair or closure. An understanding of potential
      arrhythmias, along with entrainment and high-density activation mapping can
      result in accurate diagnosis and successful ablation. Atrial fibrillation is
      being seen increasingly after patent foramen ovale closure and may be the primary
      etiology of recurrent stroke in these patients.

PMID- 28457239
TI  - Ebstein Anomaly.
AB  - Ebstein anomaly is a rare form of congenital heart disease with a uniquely high
      prevalence of arrhythmias. The most prevalent arrhythmia mechanisms are intrinsic
      to the underlying embryologic defects and may manifest at any stage. Current
      electrophysiological and surgical strategies are well equipped to address these
      arrhythmia mechanisms, yet despite available technology and a robust
      understanding of the mechanisms, these cases remain challenging. Surgical
      techniques that render arrhythmia substrates unreachable mandate comprehensive
      presurgical electrophysiological assessment and potential ablation. As the
      population ages, the need to address atrial fibrillation management and risk
      stratification for sudden cardiac death becomes ever more pertinent.

PMID- 28457240
TI  - Arrhythmias Following the Mustard and Senning Operations for Dextro-Transposition
      of the Great Arteries: Clinical Aspects and Catheter Ablation.
AB  - The atrial switch operations, the Mustard and Senning procedures, performed for
      dextro-transposition of the great arteries, have largely been supplanted by the
      arterial switch operation. As such, affected patients will only exist for
      approximately 30 more years. The main arrhythmias in these patients include
      sinoatrial node dysfunction, intraatrial reentry tachycardia, and sudden death.
      Device therapy for these patients is well-established, and catheter ablation for
      atrial tachycardias is highly efficacious. The application of meticulous
      procedural planning, customization of catheter courses, and electrophysiologic
      principles to this patient group may be extended to all postoperative complex
      congenital heart patients.

PMID- 28457241
TI  - Development of Tachyarrhythmias Late After the Fontan Procedure: The Role of
      Ablative Therapy.
AB  - Patients with a Fontan circulation are at a high risk of developing a variety of
      cardiac dysrhythmias after cardiac surgery. These dysrhythmias are most often
      supraventricular tachyarrhythmias (SVT), but ventricular tachyarrhythmias (VT)
      may also occur. Mechanisms underlying SVT are variable, including both ectopic
      activity and reentry. Over time, successive SVT may be caused by different
      mechanisms. The acute success rate of ablative therapy of atrial tachyarrhythmias
      is considerably high yet during long-term follow-up 'recurrences' frequently
      occur. It is most likely that these 'recurrences' are caused by a progressive
      atrial cardiomyopathy instead of arrhythmogeneity of prior ablative lesions.

PMID- 28457242
TI  - Clinical Aspects and Ablation of Ventricular Arrhythmias in Tetralogy of Fallot.
AB  - Life expectancy of patients with rToF has considerably improved due to refined
      surgical interventions. Monomorphic fast VTs are frequently encountered in adult
      patients with rToF. The dominant substrate of VT is anatomical isthmuses bordered
      by surgical incisions, patch material and valve annuli. Substrate based ablation
      strategies aim to transect all slow conducting anatomical isthmuses (SCAI) as
      identified by electroanatomical mapping. Procedural success is defined as non
      inducibility of VT and confirmed conduction block over the SCAI resulting in long
      term VT free survival in most patients. The identification of SCAIs in rToF may
      have important implications for risk stratification and preventive treatment.

PMID- 28457243
TI  - Drug Therapy in Adult Congenital Heart Disease.
AB  - Adults with congenital heart disease are at risk for atrial and ventricular
      arrhythmias that can lead to an increased morbidity as well as mortality. When
      catheter ablation is not an option or unsuccessful, antiarrhythmic drugs are the
      mainstay of treatment. There is limited data on the use of antiarrhythmics in
      this population. The purpose of this article is to discuss the practical aspects
      of the use of antiarrhythmics in adults with congenital heart disease. Several
      tables have been provided to provide clinicians a reference for daily use.

PMID- 28457244
TI  - Catheter Ablation: General Principles and Advances.
AB  - Besides antiarrhythmic medication, there are now very good options for a
      potentially curative therapy by catheter ablation targeting the origin of the
      underlying arrhythmias in patients with complex congenital heart disease. Three
      dimensional (3D) reconstruction of tomographic imaging (MRI or computed
      tomography) is helpful to understand the underlying cardiac anatomy, identify the
      most likely target chamber, and help with planning access. Use of the available
      3D mapping systems (sequential or simultaneous acquisition) and (if available)
      more advanced navigation systems, such as remote magnetic navigation, can improve
      the acute and long-term outcomes of catheter ablation in congenital heart
      disease.

PMID- 28457245
TI  - Cardiac Arrhythmias in Adults with Congenital Heart Disease: Pacemakers,
      Implantable Cardiac Defibrillators, and Cardiac Resynchronization Therapy
      Devices.
AB  - Implanting cardiac rhythm medical devices in adults with congenital heart disease
      requires training in congenital heart disease. The techniques and indications for
      device implantation are specific to the anatomic diagnosis and state of disease
      progression. It often requires a team of physicians and is best performed at a
      specialized adult congenital heart center.

PMID- 28457246
TI  - Arrhythmia Surgery for Adults with Congenital Heart Disease.
AB  - Patients with repaired or unrepaired congenital heart anomalies are at increased
      risk for arrhythmia development throughout their lives, often paralleling the
      need for reoperations for hemodynamic residua. The ability to incorporate
      arrhythmia surgery into reoperations can result in improvement in functional
      class and decreased need for antiarrhythmic medications. Every reoperation for
      congenital heart disease can be viewed as an opportunity to assess the electrical
      and arrhythmia substrates and to intervene to improve the arrhythmias and the
      hemodynamic condition of the patient. The authors review and summarize the
      operative techniques for arrhythmia surgery that are based on the arrhythmia
      mechanisms.

PMID- 28457247
TI  - Foreword.

PMID- 28457248
TI  - Cardiac Arrhythmias in Adults with Congenital Heart Disease.

PMID- 28457249
TI  - The meanings of words.

PMID- 28457250
TI  - Logistic regression: Part 2.

PMID- 28457251
TI  - Aristotle on generosity.

PMID- 28457252
TI  - ABO certification a valuable learning experience-not a marketing tool.

PMID- 28457253
TI  - A challenge that is surmountable: Rethinking American Board of Orthodontics
      certification.

PMID- 28457254
TI  - Rethinking American Board of Orthodontics certification.

PMID- 28457255
TI  - Authors' response.

PMID- 28457256
TI  - Serum and urine insulin-like growth factor-1 as biochemical growth maturity
      indicators.

PMID- 28457257
TI  - Authors' response.

PMID- 28457258
TI  - Feasibility of yttria-stabilized zirconia.

PMID- 28457259
TI  - Correction.

PMID- 28457260
TI  - Your brother's gatekeeper.

PMID- 28457261
TI  - Evaluation of objective structured clinical examination for advanced orthodontic
      education 12 years after introduction.
AB  - INTRODUCTION: Advanced education programs in orthodontics must ensure student
      competency in clinical skills. An objective structure clinical examination has
      been used in 1 program for over a decade. The results were analyzed cross
      sectionally and longitudinally to provide insights regarding the achievement of
      competency, student growth, question difficulty, question discrimination, and
      question predictive ability. METHODS: In this study, we analyzed 218 (82 first
      year, 68 second-year, and 68 third-year classes) scores of each station from 85
      orthodontic students. The grades originated from 13 stations and were collected
      anonymously for 12 consecutive years during the first 2 decades of the 2000s. The
      stations tested knowledge and skills regarding dental relationships, analyzing a
      cephalometric tracing, performing a diagnostic skill, identifying cephalometric
      points, bracket placement, placing first-order and second-order bends, forming a
      loop, placing accentuated third-order bends, identifying problems and planning
      mixed dentition treatment, identifying problems and planning adolescent dentition
      treatment, identifying problems and planning nongrowing skeletal treatment,
      superimposing cephalometric tracings, and interpreting cephalometric
      superimpositions. Results were evaluated using multivariate analysis of variance,
      chi-square tests, and latent growth analysis. RESULTS: The multivariate analysis
      of variance showed that all stations except 3 (analyzing a cephalometric tracing,
      forming a loop, and identifying cephalometric points) had significantly lower
      mean scores for the first-year student class than the second- and third-year
      classes (P <0.028); scores between the second- and third-year student classes
      were not significantly different (P >0.108). The chi-square analysis of the
      distribution of the number of noncompetent item responses decreased from the
      first to the second years (P <0.0003), from the second to the third years (P
      <0.0042), and from the first to the third years (P <0.00003). The latent growth
      analysis showed a wide range of difficulty and discrimination between questions.
      It also showed continuous growth for some areas and the ability of 6 questions to
      predict competency at greater than the 80% level. CONCLUSIONS: Objective
      structure clinical examinations can provide a method of evaluating student
      performance and curriculum impact over time, but cross-sectional and longitudinal
      analyses of the results may not be complementary. Significant learning appears to
      occur during all years of a 3-year program. Valuable questions were both easy and
      difficult, discriminating and not discriminating, and came from all domains:
      diagnostic, technical, and evaluation/synthesis.

PMID- 28457262
TI  - Prevalence of gingival recession after orthodontic tooth movements.
AB  - INTRODUCTION: This study was designed to evaluate the long-term prevalence of
      gingival recession after orthodontic tooth movements, focusing on the effects of
      mandibular incisor proclination and expansion of maxillary posterior teeth.
      METHODS: Records of 205 patients (162 female, 43 male) were obtained from 2
      private practice orthodontists. Using pretreatment (age, 14.0 +/- 5.9 years) and
      posttreatment (age, 16.5 +/- 6.0 years) lateral cephalograms and dental models,
      mandibular incisor proclination and maxillary arch widths were measured. Gingival
      recession was measured based on posttreatment and postretention (age, 32.3 +/-
      8.5 years) intraoral photographs and models. Associations between tooth movements
      and gingival recession were evaluated statistically. RESULTS: Only 5.8% of teeth
      exhibited recession at the end of orthodontic treatment (only 0.6% had recession
      >1 mm). After retention, 41.7% of the teeth showed recession, but the severity
      was limited (only 7.0% >1 mm). There was no relationship between mandibular
      incisor proclination during treatment and posttreatment gingival recession.
      Incisors that finished treatment angulated (IMPA) at 95 degrees  or greater did
      not show significantly more recession than did those that finished less than 95
      degrees . There were weak positive correlations (r = 0.17-0.41) between maxillary
      arch width increases during treatment and posttreatment recession. CONCLUSIONS:
      Orthodontic treatment is not a major risk factor for the development of gingival
      recession. Although greater amounts of maxillary expansion during treatment
      increase the risks of posttreatment recession, the effects are minimal.

PMID- 28457263
TI  - Survival of labial inversely impacted maxillary central incisors: A retrospective
      cone-beam computed tomography 2-year follow-up.
AB  - INTRODUCTION: The aim of this study was to analyze the development and stability
      of roots and alveolar bone in orthodontically treated labial inversely impacted
      maxillary central incisors in a long-term follow-up by cone-beam computed
      tomography. Comparisons were made between the labial inversely impacted maxillary
      central incisors after treatment and normally erupted mature contralateral
      incisors. METHODS: The sample consisted of 12 participants, with a mean age of
      7.80 +/- 0.91 years. Cone-beam computed tomography scanning data at the
      completion of treatment and the long-term follow-up were available for each
      participant.The mean length of follow-up was 24.57 +/- 4.33 months. Root length,
      crown height, root canal width, labial/lingual alveolar bone vertical loss, and
      bone thickness of the impacted and contralateral incisors were measured with the
      SimPlant Pro program (version 13.0; Materialise Dental, Leuven, Belgium).
      RESULTS: In the follow-up, the root lengths of both the labial inversely impacted
      dilacerated maxillary central incisors (10.99 +/- 1.96 mm) and the contralateral
      mature maxillary central incisors (11.65 +/- 1.37 mm) were significantly longer
      than at posttreatment (8.37 +/- 1.74 mm and 9.81 +/- 1.65 mm, respectively). The
      root canal widths of the impacted and contralateral incisors were significantly
      narrower during the follow-up. The size of the angle between the long axis of the
      crown and apical third of the root decreased significantly. The lingual alveolar
      bone loss of the impacted incisors was greater than that of the contralateral
      incisors. The labial bone thickness at the apex of the impacted incisors
      increased significantly during the follow-up period. CONCLUSIONS: The treated
      labial inversely impacted maxillary central incisors had continuous and similar
      growth as did the mature contralateral incisors in the follow-up period. The
      roots had an increase in length and a change in direction of the apex, with a
      relatively stable condition of the surrounding alveolar bone. Neither the labial
      inversely impacted maxillary central incisors nor the contralateral incisors had
      further alveolar bone loss.

PMID- 28457264
TI  - Mesial and distal alveolar bone morphology in maxillary canines moved into the
      grafted alveolar cleft: Computed tomography evaluation.
AB  - INTRODUCTION: The aims of this study were to qualitatively assess the mesial and
      distal alveolar bone of maxillary canines mesially moved to replace absent
      lateral incisors in patients with unilateral cleft lip and palate after secondary
      alveolar bone graft and to assess the reproducibility of the proposed cone-beam
      computed tomography (CBCT) method. METHODS: The sample comprised CBCT
      examinations of 30 patients with unilateral cleft lip and palate from 1 center.
      CBCT images were taken at least 6 months after comprehensive orthodontic
      treatment. The noncleft side was used as the control group. Using axial sections,
      scores from 0 to 4 (bone absence to complete bone filling, respectively) were
      given to the mesial and distal alveolar bones of the maxillary canines.
      Interexaminer and intraexaminer reproducibility was assessed using kappa
      statistics. Intergroup comparisons were performed using Wilcoxon tests. RESULTS:
      Interexaminer and intraexaminer agreement was excellent. Intergroup comparison
      identified smaller scores at the cervical and middle root levels of the cleft
      side mesial alveolar bone of the maxillary canines. At the cleft side, 85 mesial
      sites showed favorable scores (3 or 4); 1 had a score of 1, and 4 had scores of
      2. At the distal surface, 78 sites were evaluated, and only 1 site received a
      score of 1. The noncleft side had scores of 4 for all sites. CONCLUSIONS: The new
      CBCT scale showed good reproducibility. CBCT axial sections are reliable for a
      qualitative appraisal of alveolar bone in a grafted alveolar cleft. Mesial bone
      defects can be observed in maxillary canines moved into grafted areas after
      comprehensive orthodontic treatment, especially at the cervical root half.

PMID- 28457265
TI  - Anatomic landmarks and availability of bone for placement of orthodontic mini
      implants for normal and short maxillary body lengths.
AB  - INTRODUCTION: Increasing numbers of orthodontic mini-implants are placed in the
      anterior maxilla. To our knowledge, bone levels and root proximity of patients
      with cephalometrically short maxillae have not been investigated before. The
      first, second, and third rugae were used as clinical reference lines, and the aim
      of this study was to measure bone availability in that area by comparing patients
      with short and normal maxillary body lengths. METHODS: The sample consisted of 21
      patients in each group: short maxillary body length and normal maxillary body
      length. The patients' study models were bisected, and the outline of the palatal
      contour was marked on the surface. The models were scanned, and the palatal
      contours were superimposed on the palatal structures of their respective initial
      cephalometric headfilms, and the vertical and oblique bone levels of the sagittal
      plane were compared using the Student t test. The level of significance was set
      at P <0.05. RESULTS: Compared with maxillae of normal maxillary body length, less
      bone was available in maxillae of short maxillary body length. However, the
      differences did not reach clinical or statistical significance (P >0.05) at the
      third rugae. CONCLUSIONS: Almost equivalent average bone depth at the third rugae
      in patients with normal and short maxillary body lengths suggests that this site
      can be used for 8-mm long obliquely inserted orthodontic mini-implants.

PMID- 28457267
TI  - Cervical vertebral maturation: An objective and transparent code staging system
      applied to a 6-year longitudinal investigation.
AB  - INTRODUCTION: To date, little information is available regarding individual
      cervical vertebral maturation (CVM) morphologic changes. Moreover, contrasting
      results regarding the repeatability of the CVM method call for the use of
      objective and transparent reporting procedures. In this study, we used a rigorous
      morphometric objective CVM code staging system, called the "CVM code" that was
      applied to a 6-year longitudinal circumpubertal analysis of individual CVM
      morphologic changes to find cases outside the reported norms and analyze
      individual maturation processes. METHODS: From the files of the Oregon Growth
      Study, 32 subjects (17 boys, 15 girls) with 6 annual lateral cephalograms taken
      from 10 to 16 years of age were included, for a total of 221 recordings. A
      customized cephalometric analysis was used, and each recording was converted into
      a CVM code according to the concavities of cervical vertebrae (C) C2 through C4
      and the shapes of C3 and C4. The retrieved CVM codes, either falling within the
      reported norms (regular cases) or not (exception cases), were also converted into
      the CVM stages. RESULTS: Overall, 31 exception cases (14%) were seen. with most
      of them accounting for pubertal CVM stage 4. The overall durations of the CVM
      stages 2 to 4 were about 1 year, even though only 4 subjects had regular annual
      durations of CVM stages 2 to 5. CONCLUSIONS: Whereas the overall CVM changes are
      consistent with previous reports, intersubject variability must be considered
      when dealing with individual treatment timing. Future research on CVM may take
      advantage of the CVM code system.

PMID- 28457266
TI  - Effects of monocortical and bicortical mini-implant anchorage on bone-borne
      palatal expansion using finite element analysis.
AB  - INTRODUCTION: Bone-borne palatal expansion relies on mini-implant stability for
      successful orthopedic expansion. The large magnitude of applied force experienced
      by mini-implants during bone-borne expansion may lead to high failure rates. Use
      of bicortical mini-implant anchorage rather than monocortical anchorage may
      improve mini-implant stability. The aims of this study were to analyze and
      compare the effects of bicortical and monocortical anchorages on stress
      distribution and displacement during bone-borne palatal expansion using finite
      element analysis. METHODS: Two skull models were constructed to represent
      expansion before and after midpalatal suture opening. Three clinical situations
      with varying mini-implant insertion depths were studied in each skull model:
      monocortical, 1-mm bicortical, and 2.5-mm bicortical. Finite element analysis
      simulations were performed for each clinical situation in both skull models. Von
      Mises stress distribution and transverse displacement were evaluated for all
      models. RESULTS: Peri-implant stress was greater in the monocortical anchorage
      model compared with both bicortical anchorage models. In addition, transverse
      displacement was greater and more parallel in the coronal plane for both
      bicortical models compared with the monocortical model. Minimal differences were
      observed between the 1-mm and the 2.5-mm bicortical models for both peri-implant
      stress and transverse displacement. CONCLUSIONS: Bicortical mini-implant
      anchorage results in improved mini-implant stability, decreased mini-implant
      deformation and fracture, more parallel expansion in the coronal plane, and
      increased expansion during bone-borne palatal expansion. However, the depth of
      bicortical mini-implant anchorage was not significant.

PMID- 28457268
TI  - Movement of mandibular molar into edentulous alveolar ridge: A cone-beam computed
      tomography study.
AB  - INTRODUCTION: The purpose of this study was to evaluate the thickness and height
      of buccal and lingual alveolar bone of mandibular teeth moved to edentulous areas
      with a remodeled alveolar ridge. METHODS: The sample included 18 adult patients
      with unilateral or bilateral absence of mandibular permanent first molars with a
      mean age of 36.1 years before treatment. The mandibular hemiarches were divided
      into 3 groups: reopening group (15 hemiarches), closure group (12 hemiarches),
      and control group (9 hemiarches with no missing teeth). Cone-beam computed
      tomography scans with a 0.2-mm voxel size were performed 4 months after space
      closure or reopening. Cross sections 0.2 mm thick passing through the center of
      the mandibular permanent second molar and second premolar roots were used for
      measurements of the buccal and lingual bone plate thickness and level. Intergroup
      comparisons were performed with 1-way analysis of variance followed by Tukey
      tests (P <0.05). RESULTS: No intergroup differences were found for the alveolar
      bone statuses of the mandibular second premolar. For the mandibular second molar,
      the closing group showed significantly smaller buccal and lingual crest levels
      compared with the control group. CONCLUSIONS: Space closure of missing mandibular
      first molars caused slight buccal and lingual dehiscences at the mandibular
      second molar areas.

PMID- 28457269
TI  - Longitudinal cephalometric growth of untreated subjects with Class II Division 2
      malocclusion.
AB  - INTRODUCTION: Our objective was to evaluate the craniofacial growth of subjects
      with untreated Class II Division 2 malocclusion. METHODS: A mixed longitudinal
      sample of 39 white Class II Division 2 subjects was analyzed at 5 time points: T1
      (6 or 7 years), T2 (9 or 10 years), T3 (12 or 13 years), T4 (15 or 16 years), and
      T5 (18 or 19 years). They were compared with an age- and sex- matched sample of
      Class I controls. Seventeen measurements (12 angular, 5 proportional) were
      computed. Multilevel modeling procedures were used to statistically describe the
      growth changes and to evaluate group differences. RESULTS: There were no group
      differences in the relative sizes and anteroposterior positions of the jaws
      during childhood, adolescence, or early adulthood. Subjects with Class II
      Division 2 malocclusion demonstrated significantly (P <0.05) smaller mandibular
      plane angles, smaller palatal-to-mandibular plane angles, larger posterior-to
      anterior facial height ratios, smaller gonial angles, smaller cranial base
      angles, larger interincisal angles, and more retroclined maxillary incisors than
      did the Class I subjects. The hypodivergent patterns were established early and
      became more pronounced over time. Group differences in the mandibular plane
      angle, palatal-to-mandibular plane angle, gonial angle, interincisal angle, and
      maxillary incisor-to-cranial base angle, as well as the posterior-to-anterior
      facial height ratio all increased over time; the difference in the cranial base
      angle remained unchanged over time. Retroclination of the maxillary incisors
      occurred primarily during the early mixed dentition. CONCLUSIONS: Subjects with
      Class II Division 2 malocclusion are more hypodivergent and have more upright
      maxillary incisors than do subjects with Class I occlusion. Hypodivergence
      establishes itself early and increases progressively through early adulthood;
      maxillary incisor retroclination occurs early.

PMID- 28457270
TI  - Buccolingual angulation and intermolar width changes in the maxillary first
      molars of untreated growing children.
AB  - INTRODUCTION: Buccolingual inclinations of the maxillary permanent molars and
      intermolar widths increase with growth for Class I subjects. Changes for
      untreated Class II subjects have not yet been assessed. The aim of this study was
      to test the hypothesis that changes in palatal inclination of the maxillary
      molars and intermolar width throughout growth vary between Class I and Class II
      molar occlusions. METHODS: Patients were selected from the Forsyth/Moorrees Twin
      Study. Dental models taken for 6 consecutive years of 55 untreated subjects (28
      with Angle Class I and 27 with Angle Class II occlusion) were scanned. The images
      were superimposed on the palatal rugae, and the angle between a reference plane
      and the buccolingual inclination plane was used to calculate the buccolingual
      molar inclination at each time point. The distance between lingual groove points
      was used to calculate the intermolar width. RESULTS: All molars showed increasing
      palatal inclinations over the 6 years. The change for each time interval was
      statistically significant. Class I subjects demonstrated significantly greater
      palatal inclination at each time point. The molar inclination changed by means of
      4.99 degrees  for Class I subjects and 6.25 degrees  for Class II subjects.
      Intermolar width increased continuously (P <0.001) and was significantly greater
      (P <0.05) for Class I patients. CONCLUSIONS: These results suggest that palatal
      inclination of the maxillary permanent first molars occurs continuously between
      ages 9 and 14 years, with Class II subjects showing greater changes. The
      intermolar width increases steadily during this time, with Class II subjects
      having a narrower intermolar width and less change over time.

PMID- 28457271
TI  - Relationships among nasal resistance, adenoids, tonsils, and tongue posture and
      maxillofacial form in Class II and Class III children.
AB  - INTRODUCTION: The purpose of this study was to clarify the relationships between
      upper airway factors (nasal resistance, adenoids, tonsils, and tongue posture)
      and maxillofacial forms in Class II and III children. METHODS: Sixty-four
      subjects (mean age, 9.3 years) with malocclusion were divided into Class II and
      Class III groups by ANB angles. Nasal resistance was calculated using
      computational fluid dynamics from cone-beam computed tomography data. Adenoids,
      tonsils, and tongue posture were evaluated in the cone-beam computed tomography
      images. The groups were compared using Mann-Whitney U tests and Student t tests.
      The Spearman rank correlations test assessed the relationships between the upper
      airway factors and maxillofacial form. RESULTS: Nasal resistance of the Class II
      group was significantly larger than that of the Class III group (P = 0.005).
      Nasal resistance of the Class II group was significantly correlated with inferior
      tongue posture (P <0.001) and negatively correlated with intermolar width (P =
      0.028). Tonsil size of the Class III group was significantly correlated with
      anterior tongue posture (P <0.001) and mandibular incisor anterior position (P =
      0.007). Anterior tongue posture of the Class III group was significantly
      correlated with mandibular protrusion. CONCLUSIONS: The relationships of upper
      airway factors differ between Class II and Class III children.

PMID- 28457272
TI  - Three-dimensional upper airway changes with mandibular advancement device in
      patients with obstructive sleep apnea.
AB  - INTRODUCTION: A mandibular advancement device effectively increases upper airway
      size in patients with obstructive sleep apnea. Three-dimensional volumetric upper
      airway changes, exact amounts of change in obstructed upper airways (smallest
      cross-sectional area), and anteroposterior and transverse changes with mandibular
      advancement devices are not clear. METHODS: Thirty-seven patients with
      obstructive sleep apnea diagnosed with polysomnography were evaluated with the
      subjective Epworth sleepiness scale, percentage of oxygen saturation, and cone
      beam computed tomography. Parameters were airway volume, smallest cross-section
      area, anteroposterior width, and transverse width of the upper airway. Patients
      received a mandibular advancement device, a Twin-block appliance that could be
      titrated with a jackscrew; posttreatment data were collected after 6 months.
      RESULTS: A statistically significant improvement in mean oxygen saturation level
      was observed, from 87.97% +/- 4.43% to 94.89% +/- 1.54% (P <0.001). A significant
      mean increase in airway volume of 2360 +/- 2050 mm3 (P <0.001) was observed, from
      12140 +/- 4773 mm3 to 14500 +/- 5114.6 mm3. A stastistically significant mean
      increase in the smallest cross section of 46.55 +/- 31.62 mm2, from 81.95 +/-
      55.23 mm2 to 128.5 +/- 54.78 mm2 was observed. Anteroposterior width increased
      significantly, from 4.99 +/- 1.65 mm to 8.01 +/- 2.04 mm. Transverse width
      increased significantly, from 27.67 +/- 8.52 mm to 31.94 +/- 8.59 mm.
      CONCLUSIONS: Mandibular advancement devices increased the mean upper pharyngeal
      airway volume in this cohort, and this increase in volume appeared to be related
      to increased oxygen saturation.

PMID- 28457273
TI  - Addition of ammonium-based methacrylates to an experimental dental adhesive for
      bonding metal brackets: Carious lesion development and bond strength after
      cariogenic challenge.
AB  - INTRODUCTION: In this study, we evaluated the caries inhibition and shear bond
      strength achieved with the addition of the antibacterial monomer [2
      (Methacryloyloxy)ethyl] trimethylammonium chloride (MADQUAT) to an adhesive used
      to bond orthodontic brackets. METHODS: Experimental adhesives were formulated
      with addition of 0% (control), 5%, or 10% MADQUAT followed by measurement of the
      degree of conversion. These adhesives were used to lute brackets to the enamel of
      premolars (n = 30). Biofilm from a microcosm model was cultivated in half of the
      specimens under cariogenic challenge for 5 days. The brackets were subjected to a
      shear bond strength test followed by measurement of the internal hardness of the
      enamel around the brackets to calculate the integrated mineral loss. RESULTS: The
      addition of MADQUAT slightly increased the degree of conversion. Adhesive
      containing 10% MADQUAT significantly reduced the integrated mineral loss around
      the bracket but also resulted in the lowest values of bond strength. No effects
      on bond strength and integrated mineral loss were observed with the addition of
      5% MADQUAT to the adhesive. The cariogenic challenge did not affect the bond
      strength and the failure mode. CONCLUSIONS: MADQUAT was effective to reduce the
      integrated mineral loss only when added to the adhesive at a concentration of 10%
      despite the reduction of bond strength.

PMID- 28457274
TI  - Cytotoxic outcomes of orthodontic bands with and without silver solder in
      different cell lineages.
AB  - INTRODUCTION: The safety of orthodontic materials is a matter of high interest.
      In this study, we aimed to assess the in-vitro cytotoxicity of orthodontic band
      extracts, with and without silver solder, by comparing the viability outcomes of
      the HaCat keratinocytes, the fibroblastic cell lineages HGF and MRC-5, and the
      kidney epithelial Vero cells. METHODS: Sterilized orthodontic bands with and
      without silver solder joints were added to culture media (6 cm2/mL) and incubated
      for 24 hours at 37 degrees C under continuous agitation. Subsequently, the cell
      cultures were exposed to the obtained extracts for 24 hours, and an assay was
      performed to evaluate the cell viability. Copper strip extracts were used as
      positive control devices. RESULTS: The extracts from orthodontic bands with
      silver solder joints significantly reduced the viability of the HaCat, MRC-5, and
      Vero cell lines, whereas the viability of HGF was not altered by this material.
      Conversely, the extracts of orthodontic bands without silver solder did not
      significantly modify the viability index of all evaluated cell lines.
      CONCLUSIONS: Except for HGF fibroblasts, all tested cell lines showed decreased
      viability percentages after exposure to extracts of orthodontic bands containing
      silver solder joints. These data show the relevance of testing the toxicity of
      orthodontic devices in different cell lines.

PMID- 28457275
TI  - Nonsurgical treatment of severe Class II malocclusion with anterior open bite
      using mini-implants and maxillary lateral incisor and mandibular first molar
      extractions.
AB  - This clinical case report presents the nonsurgical orthodontic treatment of a
      patient with skeletal Class II malocclusion, posterior crossbite, anterior open
      bite, accentuated dental discrepancies in both arches, and an odontoma. The
      proposed treatment involved maxillary expansion, extraction of atypical maxillary
      lateral incisors and mandibular first molars, and intrusion of maxillary teeth
      with the aid of mini-implants. The results obtained with these procedures
      included good tooth alignment, normal overbite and overjet, removal of the
      odontoma, and a harmonious smile. In complex cases, an accurate diagnosis is the
      key to a favorable outcome.

PMID- 28457277
TI  - Semipermanent replacement of missing maxillary lateral incisors by mini-implant
      retained pontics: A follow-up study.
AB  - Agenesis of maxillary lateral incisors can be treated either by closing the space
      and substituting the canines for the missing lateral incisors or, in adults, by
      replacing the missing teeth with fixed prosthetics or implants. This article
      illustrates a method that can be used for a semipermanent implant replacement of
      the missing incisors in adult patients. An Aarhus mini-implant was inserted
      perpendicular to the palatal mucosa of the alveolar process of the edentulous
      area. A pontic was made at chair side of composite material around a stainless
      steel wire extending from the mini-implant. This replacement approach allowed for
      the vertical development of the alveolar process and maintained the bone density
      and morphology of the alveolar process. Five years after placement, periapical
      radiographs showed that the alveolar process was following the vertical
      development related to the eruption of the adjacent teeth, and that the
      morphology and the bone density were maintained, making the later insertion of a
      dental implant possible without additional surgical buildup.

PMID- 28457276
TI  - Nonsurgical correction using miniscrew-assisted vertical control of a severe high
      angle with mandibular retrusion and gummy smile in an adult.
AB  - Orthodontic treatment in adult patients with a skeletal discrepancy can be
      challenging. In this case report, we achieved both sagittal and vertical control
      by combining the classic sliding mechanics straight-wire technique with miniscrew
      anchorage. We treated a 21-year-old Chinese woman with a severe high mandibular
      plane angle, a retrusive chin, and a gummy smile. Her diagnosis included a
      skeletal Class II skull base with a mild anterior open bite, a protrusive
      maxilla, and a backwardly rotated mandible. This case underscores the importance
      of anchorage control in both the sagittal and vertical directions. First, we used
      miniscrews in the maxillary and mandibular buccal segments to obtain rigid
      anchorage. Next, we achieved good anterior and posterior vertical control with
      miniscrews in the maxillary anterior labial and posterior buccolingual segments.
      Intrusion of the maxillary molars contributed to deepening of the anterior
      overbite and counterclockwise rotation of the mandibular plane, which, in turn,
      improved the facial profile. Intrusion of the maxillary incisors contributed to
      correction of the gummy smile. After 1 year of retention, the patient had a
      stable, well-aligned dentition with ideal intercuspation and an improved facial
      contour. Our results thus suggest that placement of miniscrews in the anterior
      and posterior regions of the maxilla is effective for camouflaging a high-angle
      skeletal Class II defect. This technique requires minimal patient compliance and
      is particularly useful for correction of a high angle in an adult with a gummy
      smile.

PMID- 28457278
TI  - Accuracy of a computed tomography scanning procedure to manufacture digital
      models.
AB  - INTRODUCTION: Accurate articulation of the digital dental casts is crucial in
      orthodontic diagnosis and treatment planning. We aimed to determine the accuracy
      of manufacturing digital dental casts from computed tomography scanning of
      plaster casts regarding linear dimensions and interarch relationships and to test
      whether eventual differences in interarch relationships between plaster and
      digital casts would affect orthodontic diagnostics. METHODS: Plaster casts with
      the wax bites of 2 patients were used to create digital dental casts with a
      computed tomography scanner. This was repeated 4 times with a 1-week interval.
      Linear distances were measured on plaster and digital models twice by 2
      observers. Next, the 4 digital models of each patient were scored twice by 5
      observers for interarch variables. RESULTS: Digital vs plaster measurements
      showed high Pearson correlation coefficients (>0.954), whereas the mean
      difference was small (<0.1 mm) and not significant. The interarch scorings,
      however, showed significant differences for all variables, except overjet for
      model 1. CONCLUSIONS: We found substantial interarch inaccuracies of the digital
      models. These inaccuracies are probably due to a lack of built-in "collision
      control" in the software and manual articulation of the digital models by a human
      operator.

PMID- 28457279
TI  - [Palpate that mouth which I may not behold].

PMID- 28457280
TI  - The importance of validation in ophthalmic medical claims database research.

PMID- 28457281
TI  - Refractive predictability of a 3-piece intraocular lens platform versus its 1
      piece counterpart.
AB  - OBJECTIVE: To compare the refractive outcomes of a 3-piece acrylic intraocular
      lens (IOL) with its 1-piece counterpart after phacoemulsification with in-the-bag
      implantation. DESIGN: Retrospective chart review. PARTICIPANTS: One-hundred
      twenty-six eyes of 95 patients were analyzed in the study, including 60 eyes of
      43 patients receiving a 3-piece IOL and 66 eyes of 52 patients receiving a 1
      piece IOL. METHODS: Randomized chart review of all patients who underwent
      uncomplicated phacoemulsification with in-the-bag IOL implantation with either a
      3-piece hydrophobic acrylic IOL (Tecnis ZA9003) or a 1-piece hydrophobic acrylic
      IOL (Tecnis ZCB00) between 2006 and 2014 in a tertiary ophthalmology care centre
      in Mississauga, Ontario. Preoperative visual acuity and refraction, anterior
      chamber depth, axial length, IOL design and power, predicted refraction,
      postoperative visual acuity, and refraction were recorded. RESULTS: Mean absolute
      error was 0.40 +/- 0.27 in the ZA9003 group and 0.39 +/- 0.35 in the ZCB00 group,
      with no statistically significant difference between the 2 IOLs (p = 0.86). Mean
      arithmetic error was 0.11 +/- 0.47 D in the ZA9003 group and 0.01 +/- 0.47 D in
      the ZCB00 group (p = 0.019). In the ZA9003 group, 23 (38%), 42 (70%), and 52
      (87%) of 60 eyes were within 0.25, 0.50, and 0.75 D, respectively, of predicted
      postoperative refraction. In the ZCB00 group, 32 (48%), 46 (70%), and 56 (85%) of
      66 eyes were within 0.25, 0.50, and 0.75 D, respectively, of predicted
      postoperative refraction (p = 0.2836, p = 1.00, p = 0.8044). CONCLUSIONS: The
      ZA9003 and the ZCB00 have similar mean absolute error and thus appear to have
      similar refractive predictability.

PMID- 28457282
TI  - Outcomes after implantable collamer lens surgery in a Canadian cohort.
AB  - OBJECTIVE: To describe refractive outcomes and complications after implantable
      collamer lens (ICL) implantation. DESIGN: Retrospective, interventional case
      series. METHODS: A database search of ICL surgeries over a 5-year period (2009
      2013) was conducted, and 83 eyes of 44 patients were included. The Visian ICL
      (STAAR Surgical, Monrovia, Calif.) was used in all eyes. The primary outcome
      measure was postoperative uncorrected distance acuity (UCDA). Secondary outcomes
      include predictability, safety, and adverse events. RESULTS: Mean age was 31
      years, and 59% of patients were female. Mean observation time was 14.9 months.
      Mean manifest refractive spherical equivalent (MRSE) was -11.1 +/- 3.24 D
      preoperatively and -0.18 D +/- 0.57 D postoperatively. Mean astigmatism was -1.90
      +/- 1.34 D, and 82% of eyes received toric ICLs, 93.4% of eyes achieved 20/40
      UCDA, and 50.8% achieved 20/20 at last observation; 67.1% and 89.5% of eyes had
      MRSE within 0.5 and 1.00 D of target refraction, respectively. Safety index was
      1.16 and overall improvement of 0.060 logMAR was observed. Eight (10.5%) eyes had
      residual astigmatism with 5 (6.5%) requiring laser enhancement. Glare and haloes
      were reported in 6 eyes (7.9%). Three eyes developed cataract. One eye had a
      retinal detachment. CONCLUSIONS: Toric and nontoric ICL implantations show
      promising refractive outcomes and acceptable safety in moderate to high myopes
      and can be considered for patients who are noncandidates for refractive laser
      surgery.

PMID- 28457283
TI  - Artisan iris-fixated intraocular lens implantation in combination with
      pupilloplasty-correction of aphakia with pathologically large pupil and
      insufficient capsular support.
AB  - OBJECTIVE: The aim of this study was to report the efficacy and safety of
      applying pupilloplasty in combination with Artisan iris-fixated intraocular lens
      (IOL) implantation in the treatment for aphakia with pathologically large pupil
      and insufficient capsular support. DESIGN: The study was a retrospective case
      series. PARTICIPANTS: Twenty-six aphakic eyes with pathologically large pupil and
      insufficient capsular support (from 26 patients) were included in the study.
      METHODS: The study patients underwent pupilloplasty in combination with Artisan
      iris-fixated IOL implantation. Follow-up appointments were scheduled at 1 week
      and at 1, 3, and 6 months postoperatively. RESULTS: The mean uncorrected visual
      acuity was significantly improved from logMAR 1.15 +/- 0.29 to logMAR 0.37 +/-
      0.17, and the mean manifest refraction spherical equivalent was significantly
      decreased from 12.07 +/- 2.20 D to -0.69 +/- 0.70 D at 6 month after surgery (p <
      0.05). The pupil diameter decreased significantly, from 5.7 +/- 1.1 mm
      preoperatively to 4.5 +/- 0.8 mm at 6 months after pupilloplasty (p < 0.05).
      Patients experienced less photophobia postoperatively. The safety parameters,
      including endothelial cell count, intraocular pressure, corneal astigmatism, best
      corrected visual acuity, and central corneal thickness, showed no significant
      differences in values before and after surgery. CONCLUSIONS: The Artisan iris
      fixated IOL implantation in combination with pupilloplasty can be used as an
      alternative way to correct aphakia with pathologically large pupil and
      insufficient capsular support.

PMID- 28457284
TI  - Corneal surgery in the flying eye hospital: characteristics and visual outcome.
AB  - OBJECTIVE: The Flying Eye Hospital (FEH) of ORBIS International is a capacity
      building platform that trains ophthalmologists throughout the developing world on
      board a fully functional eye hospital based in an airplane and in the local
      hospitals of developing countries. Corneal blindness (CB) is the second leading
      cause of blindness in most developing countries. Treatment of existing global CB
      requires effective eye banking and surgeons trained in corneal transplant. ORBIS
      International has programs that addressed both those needs. This study reports
      the clinical outcome of all keratoplasty training programs of the FEH from
      January 2010 to December 2014. METHODS: Surveys were sent to all local
      ophthalmologists trained on FEH to perform keratoplasty in the relevant time
      period. The survey included patient demographics, procedure performed,
      indications for surgery, postoperative steroid regiment, and visual acuity (VA).
      RESULTS: Keratoplasty was undertaken in 87 eyes as follows: penetrating
      keratoplasty (PK) in 66 (75.9% of our population), deep anterior lamellar
      keratoplasty (DALK) in 6 (6.9%), Descemet's stripping endothelial keratoplasty
      (DSEK) in 14 (16.1%), and Boston keratoprosthesis (KP) in 1 (1.1%). Corneal
      clouding was the indication in 83 (95.4%) of patients. Forty-seven (54%) patients
      returned for long-term care with the mean follow-up (FU) of 32.0 months (range 6
      60 months). Thirteen (27.7%) were not using any steroids at last the FU. Eleven
      (23.4%) patients had signs of graft rejection. Best-corrected VA in meters and
      feet, respectively, was 6/6 to 6/18 (20/20 to 20/60) in 12 (25.5%) patients, 6/18
      to 6/60 (20/60 to 20/200) in 19 (40.4%) patients, 6/60 to 3/60 (20/200 to 20/400)
      in 4 (8.5%) patients, and less than 3/60 (20/400) in 12 (25.5%) patients.
      CONCLUSION: Clinical outcomes delivered by FEH keratoplasty training are
      acceptable compared to results in the developing world and to some reports of
      training programs in the developed world, though our study is limited by its
      retrospective nature and the poor rate of FU.

PMID- 28457285
TI  - Repeatability, reproducibility, agreement characteristics of 2 SD-OCT devices for
      anterior chamber angle measurements.
AB  - OBJECTIVE: To evaluate the agreement, reproducibility, and repeatability of 2
      spectral domain optical coherence tomography (SD-OCT) devices in Schwalbe's line
      (SL)-based anterior chamber angle parameters. METHODS: The inferior anterior
      chamber angle of 65 eyes from 65 participants (33 right eyes and 32 left eyes)
      were scanned twice with the Nidek RS 3000 Advanced SD-OCT and Cirrus SD-OCT. SL
      angle opening distance (SL-AOD) and SL trabecular-iris-space area (SL-TISA) were
      graded by masked certified graders at the Doheny Image Reading Center. RESULTS:
      The mean SL-AOD/SL-TISA was 617.3 +/- 237.9 um/0.211 +/- 0.086 mm2 for the Cirrus
      and 633.7 +/- 219.3 um/0.218 +/- 0.080 mm2 for the Nidek RS 3000 Advanced SD-OCT.
      The repeatability (intraclass correlation coefficients [ICCs] >0.936) and
      intergrader reproducibility (ICCs >0.915) in SL-AOD and SL-TISA with Cirrus OCT
      were excellent. The repeatability (ICCs >0.948) and intergrader reproducibility
      (ICCs >0.709) in SL-AOD and SL-TISA with the Nidek RS 3000 Advanced SD-OCT were
      moderate to good. Moderate agreement between the 2 devices was also documented
      with a mean difference of -15.3 (limits of agreement [LoA] -246.5 to 277.1) mm
      for SL-AOD and 0.006 (LoA -0.096 to 0.108) mm in SL-TISA. CONCLUSION: Both
      devices were able to provide consistent angle measurements, but repeatability and
      reproducibility were better in Cirrus SD-OCT than in Nidek RS 3000 Advanced SD
      OCT.

PMID- 28457286
TI  - Quantitative analysis of the text and graphic content in ophthalmic slide
      presentations.
AB  - OBJECTIVE: To determine the characteristics of ophthalmic digital slide
      presentations. DESIGN: Retrospective quantitative analysis. METHODS: Slide
      presentations from a 2015 Canadian primary eye care conference were analyzed for
      their duration, character and word count, font size, words per minute (wpm),
      lines per slide, words per slide, slides per minute (spm), text density product
      (wpm * spm), proportion of graphic content, and Flesch Reading Ease (FRE) score
      using Microsoft PowerPoint and Word. The median audience evaluation score for the
      lectures was used to dichotomize the higher scoring lectures (HSL) from the lower
      scoring lectures (LSL). A priori we hypothesized that there would be a difference
      in the wpm, spm, text density product, and FRE score between HSL and LSL.
      Wilcoxon rank-sum tests with Bonferroni correction were utilized. RESULTS: The 17
      lectures had medians of 2.5 spm, 20.3 words per slide, 5.0 lines per slide, 28
      point sans serif font, 36% graphic content, and text density product of 136.4
      words * slides/minute2. Although not statistically significant, the HSL had more
      wpm, fewer words per slide, more graphics per slide, greater text density, and
      higher FRE score than LSL. There was a statistically significant difference in
      the spm of the HSL (3.1 +/- 1.0) versus the LSL (2.2 +/- 1.0) at p = 0.0124.
      CONCLUSION: All presenters showed more than 1 slide per minute. The HSL showed
      more spm than the LSL. The descriptive statistics from this study may aid in the
      preparation of slides used for teaching and conferences.

PMID- 28457288
TI  - The use of semistructured interviews to assess quality of life impacts for
      patients with uveal melanoma.
AB  - OBJECTIVE: There are limited studies on uveal melanoma and patient quality of
      life. However, the burden of implementing a patient-reported outcome measure to
      collect this information in a clinical setting is unknown. The objectives of this
      study were (i) to understand the issues of quality of life that are most
      important to patients undergoing treatment for uveal melanoma, (ii) to explore
      patient views on the European Organization for Research and Treatment of Cancer's
      (EORTC) ophthalmic oncology quality of life questionnaire (QLQ-OPT30), and (iii)
      to assess patient willingness to complete questionnaires measuring quality of
      life on an ongoing basis. DESIGN: This was a qualitative study. PARTICIPANTS: The
      study included 10 patients treated for uveal melanoma with brachytherapy at the
      Alberta Ocular Brachytherapy Program, with a mean follow-up period of 16.3 months
      (range 5-33 months) after diagnosis. METHODS: The participants completed a
      qualitative interview over the phone with a trained interviewer between November
      2014 and January 2015. Participants completed the QLQ-OPT30 according to their
      current symptoms and then elaborated on their responses. The participants then
      completed a semistructured interview to provide more information about the
      symptoms or issues that had the most impact on quality of life. RESULTS: The
      participants expressed positive feelings about the QLQ-OPT30; however, the
      participants' responses revealed that several themes, including mental health,
      impact of diagnosis and treatment on family, travel and financial burdens of
      treatment, and impact on work and home life, were missing in the questionnaire.
      CONCLUSIONS: The QLQ-OPT30 performed well, but some missing constructs were
      identified. Furthermore, participants took 23 minutes to complete the QLQ-OPT30
      with a trained interviewer, and this could present logistical challenges when
      using it at the point of care.

PMID- 28457287
TI  - Ten-year retrospective review of outcomes following phacoemulsification with
      intraocular lens implantation in patients with pre-existing uveitis.
AB  - OBJECTIVE: The aim of this study was to evaluate the visual outcome, uveitis
      control, and complications following cataract surgery for intraocular lens (IOL)
      implantation in patients with a known diagnosis of uveitis. DESIGN: The study was
      a retrospective interventional case series. PARTICIPANTS: We reviewed 98 patients
      (137 eyes) with adult uveitis undergoing cataract surgery with foldable acrylic
      posterior chamber IOL implantation between 2003 and 2013 in 2 uveitis practices.
      METHODS: Best-corrected visual acuity (BCVA) and uveitis grade (Standardized
      Uveitis Nomenclature criteria) were measured at 1 month preoperatively, at
      postoperative week 1, and at postoperative months 1, 6, and 12. The main outcome
      measures were mean change in postoperative BCVA, uveitis grade, and
      complications. RESULTS: Of the eyes studied, 84% had grade 0-0.5 anterior uveitis
      at postoperative week 1 and maintained uveitis control (77% grade 0; 19% grade
      0.5 anterior uveitis) at 1 year postoperatively. None of the patients had active
      intermediate or posterior uveitis at any time point. Mean BCVA improved from 0.71
      +/- 0.38 logMAR preoperatively to 0.37 +/- 0.36 at 6 months (p < 0.01) and to
      0.30 +/- 0.25 at 12 months (p = 0.01) postoperatively. Of the study participants,
      30% had preoperative complications related to uveitis, including epiretinal
      membrane (12%), cystoid macular edema (12%), and glaucoma (5.8%); 46% of patients
      had small pupils as a result of posterior synechiae. Postoperative vision
      limiting complications included posterior capsule opacification (18%), epiretinal
      membrane (9.0%), and cystoid macular edema (8.8%). Of the eyes studied, 5.8%
      underwent Nd:YAG capsulotomy. CONCLUSIONS: Cataract surgery with acrylic
      posterior-chamber IOL implantation is effective at improving visual acuity in
      patients with uveitis. Uveitis was well controlled in the majority of our study
      patients for 12 months after cataract surgery. The most frequent vision-limiting
      postoperative complication was posterior capsule opacification, which was
      treatable with Nd:YAG capsulotomy.

PMID- 28457289
TI  - Changes in pupillary distance after fat versus bony orbital decompression in
      Graves' orbitopathy.
AB  - OBJECTIVE: To report changes in pupillary distance (PD) after orbital
      decompression in patients with Graves' orbitopathy (GO). DESIGN: Retrospective
      comparative case series. PARTICIPANTS: A total of 59 cases who underwent the same
      type of orbital decompression on both eyes. METHODS: The medical records of 111
      patients who underwent orbital decompression were reviewed retrospectively. Fifty
      nine patients without restrictive myopathy who underwent the same procedure on
      both eyes were included. Patients were divided into the following 3 groups by
      procedure: only fat decompression (group 1, n = 18), fat and medial wall
      decompression (group 2, n = 11), and fat, medial, and inferior wall decompression
      (group 3, n = 30). Preoperative and postoperative PD and proptosis were measured.
      RESULTS: PD shortened by 2.9 mm in group 1 (p < 0.001), 2.4 mm in group 2 (p <
      0.001), and 3.5 mm in group 3 (p < 0.001). Proptosis improved by 3.5 mm in group
      1 (p < 0.001), 3.5 mm in group 2 (p < 0.001), and 4.6 mm in group 3 (p < 0.001).
      PD changes were not significantly different between the groups (p = 0.328). The
      change in PD was significantly correlated with the mean amount of proptosis
      reduction (r = 0.374, p = 0.003). CONCLUSIONS: PD shortened after orbital
      decompression in patients with fat proliferative GO. The change in PD was not
      related to the type of orbital decompression, but rather to the amount of
      proptosis reduction. Postoperative changes in PD should be considered when
      performing orbital decompression.

PMID- 28457290
TI  - Effectiveness of sodium hyaluronate (Protad) application in endoscopic endonasal
      dacryocystorhinostomy.
AB  - OBJECTIVE: To evaluate the effects of applying sodium hyaluronate solution
      (Protad) intraoperatively during endonasal dacryocystorhinostomy. METHODS: A
      retrospective medical record review of all 254 patients (254 eyes) who underwent
      endonasal dacryocystorhinostomy for nasolacrimal duct obstruction was performed.
      The success rates and postoperative complications of the Protad application group
      (105 eyes) and the control group (149 eyes) were compared. RESULTS: The Protad
      group had better anatomical (96.2% vs 86.6%, p = 0.010) and functional (93.3% vs
      85.2%, p = 0.046) surgical success rates. Granuloma developed less frequently in
      the Protad group (11.4% vs 32.9%, p < 0.001). Regarding secondary outcomes,
      synechia was less frequent in the Protad group, but the difference was not
      statistically significant (p = 0.283). Crust and infection rates were also lower
      in the Protad group (6.7% vs 11.4% for crust, 7.6% vs 8.1% for infection), but
      the difference was not statistically significant (p = 0.203 and p = 0.899,
      respectively). The rate of revision surgery was significantly lower in the Protad
      group compared to the control group (1.9% vs 14.1%, p < 0.001). Granuloma had the
      largest effects on anatomical and functional surgical success (odds ratio, 72.221
      for anatomical and 19.915 for functional). CONCLUSIONS: The application of Protad
      effectively reduced postoperative granulation and enhanced surgical success rate
      after endonasal dacryocystorhinostomy. We suggest that Protad is a good nasal
      dressing material, especially for beginners in endoscopic surgery who work on
      Asian patients with narrow nasal cavities.

PMID- 28457291
TI  - Normative pediatric data for three tests of functional vision.
AB  - OBJECTIVE: To provide the normative pediatric data for three tests of functional
      vision. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: The
      participants were 281 children between 3 and 5 years of age (mean 4.2 +/- 0.8
      years) participating in a preschool vision screening study. METHODS: Participants
      completed monocular testing with the Precision Vision Visual Acuity Testing
      (PVVAT) system, a computerized test of visual acuity. Stereoacuity was assessed
      using the Pass Test 3 Stereo Test. Noncycloplegic refractive error was measured
      using the Plusoptix S09 Vision Screener (PS09). The mean and 95% tolerance limits
      were determined for each test. RESULTS: Visual acuity improved significantly from
      0.31 logMAR at 3 years to 0.18 logMAR at 5 years (p < 2.4 * 10-15). Stereoacuity
      improved from 104 arcsec at 3 years to 81 arcsec at 5 years (p = 0.0058).
      Spherical refractive error remained relatively stable at 0.29 D at 3 years and
      0.24 D at 5 years (p = 0.543). Cylindrical refractive error was also relatively
      stable, measuring 0.39 D at 3 years and 0.31 D at 5 years (p = 0.109).
      CONCLUSIONS: Both visual acuity and stereoacuity improved significantly from 3 to
      5 years of age. Note, however, that the norms obtained using the PVVAT system
      were somewhat lower than those reported in previous studies using other tests.
      The norms for the PS09 were stable and showed relatively good agreement with the
      manufacturer-suggested referral criteria.

PMID- 28457292
TI  - Visual outcomes of patients presenting with bilateral infantile cataracts and
      nystagmus.
AB  - OBJECTIVE: To evaluate the outcomes of cataract surgery in pediatric patients
      presenting with bilateral infantile cataracts and nystagmus. DESIGN:
      Retrospective case study. PARTICIPANTS: Thirteen pediatric patients who presented
      between September 2002 and February 2014 at a single tertiary care institution.
      METHODS: Patients were included if they presented with bilateral visually
      significant cataracts and preoperative manifest nystagmus and had no other
      systemic or ocular condition that could explain the presence of the nystagmus.
      Data collected included best-corrected visual acuity (BCVA), etiology of
      cataracts, associated systemic/ocular conditions, status of strabismus, surgical
      complications, and presence of nystagmus. RESULTS: Mean age at diagnosis of the
      cataracts was 8.1 +/- 10.6 months. Mean age at surgery was 8.4 +/- 10.5 months.
      Average length of follow-up was 54.3 +/- 32.6 months. Twelve patients were left
      aphakic bilaterally; 1 patient received primary intraocular lenses bilaterally.
      Ten patients were able to perform visual acuity at the most recent visit, with 5
      out of 10 having BCVA >=20/40 in the better-seeing eye. Two patients had no
      visible nystagmus and 3 patients had latent nystagmus only at the most recent
      visit. CONCLUSIONS: The presence of preoperative nystagmus does not preclude good
      visual outcomes in pediatric patients with cataracts.

PMID- 28457294
TI  - Binocular visual acuity interaction in children: summation and inhibition.
AB  - OBJECTIVE: To compare binocular visual acuity with the monocular visual acuity of
      the better eye and investigate the factors contributing to binocular interaction.
      DESIGN: Retrospective observational study. PARTICIPANTS: We enrolled 332
      children. They were divided into 3 groups according to binocular interaction:
      group A (binocular equivalency), group B (binocular summation), and group C
      (binocular inhibition). METHODS: Monocular visual acuity, binocular visual
      acuity, and stereoacuity were evaluated. The main outcome measures were the
      prevalence rates of binocular interaction and factors associated with binocular
      interaction, including monocular visual acuity of the better eye, interocular
      difference of monocular visual acuity, and stereopsis. RESULTS: Of 332 children,
      binocular summation and equivalency were noted in 218 (65.7%) and 95 (28.6%),
      respectively, and binocular inhibition in 19 (5.7%). The binocular visual acuity
      and monocular visual acuity of the better eye in group B were better than those
      in groups A and C, respectively (p = 0.000). There was a significant correlation
      between monocular visual acuity of the better eye and binocular visual acuity in
      groups B and C (r = 0.884, p = 0.000; r = 0.797, p = 0.000, respectively). The
      interocular difference of monocular visual acuity in group B (0.05 +/- 0.07) was
      smaller than that in group C (0.13 +/- 0.06) (p = 0.000). The proportion of
      children with good stereopsis was 74.3% in group B but only 31.6% in group C (p =
      0.001). CONCLUSIONS: About 66% of 332 patients had better binocular visual acuity
      than monocular visual acuity of the better eye. Our results suggest that the
      monocular visual acuity of the better eye, interocular difference of monocular
      visual acuity, and stereopsis affect binocular interaction.

PMID- 28457293
TI  - Resultats pressionnels et visuels a long terme de la sclerectomie profonde dans
      le glaucome congenital primitif.
AB  - OBJECTIVE: To estimate long term future of pressure and vision of children who
      underwent DS for CPG. MATERIAL AND METHODS: Children affected by CPG, aged from 1
      day to 3 years at the time of the diagnosis were retrospectively included between
      1999 and 2014. All benefited from a DS with use of antimetabolites. Preoperative
      and long-term post-operative intraocular pressures (IOP), per and postoperative
      complications as well as visual acuity and refractive status were estimated.
      Complete IOP control was defined by a postoperative IOP <=16 mmHg without medical
      treatment. RESULTS: 141 eyes of 71 children were included (sex ratio: 1.02). Mean
      follow-up was 56.6 +/-9.6 months. Final average IOP among the whole sample was
      11.3 +/-7 mmHg. The rate of total success was 69.4 %, partial success 27.6 % and
      3 % failure at the last check. No complications were seen in 85.1 % of cases
      (n=120 eyes). Among 37 children analyzed for visual acuity, maintained visual
      acuity was found in 50 % of cases (n= 37 eyes). CONCLUSION: DS allows obtaining
      good IOP control with a very low rate of complications, and should be considered
      as a technique of choice in the surgical management of CPG. This study is of
      particular relevance because it has been led on a long term period and on an
      important staff considering the rare prevalence of the condition.

PMID- 28457295
TI  - Relationship between vitamin D deficiency and diabetic retinopathy: a meta
      analysis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the evidence for an
      association between diabetic retinopathy (DR) and vitamin D deficiency. DESIGN:
      Meta-analysis. METHODS: We included 14 observational studies with 10 007
      participants who had undergone assessment for both DR and vitamin D deficiency.
      Pooled odds ratios (ORs) and 95% CIs were calculated using a random-effect,
      Mantel-Haenszel analysis. RESULTS: There was a statistically significant
      association between DR and vitamin D deficiency with an overall pooled OR of 1.27
      (95% CI, 1.17-1.37; P = 0.001; I2 = 80%; Pheterogeneity = 0.01). There was also a
      statistically significant lower serum vitamin D level in patient subgroups with
      DR versus control groups, with an overall mean difference of -1.32 ng/mL (95% CI,
      -2.50 to -0.15; P = 0.001; I2 = 89%; Pheterogeneity = 0.01). CONCLUSION: There is
      a statistically significant association between vitamin D deficiency and DR.

PMID- 28457296
TI  - The role of occult hypertension in retinal vein occlusions and diabetic
      retinopathy.
AB  - OBJECTIVE: The aim of the study was to investigate whether individuals who
      develop retinal vein occlusion (RVO) or sudden-onset activity in otherwise
      quiescent diabetic retinopathy (DR) and those who have normal blood pressure (BP)
      or controlled hypertension according to their family physician show evidence of
      occult hypertension on 24-hour BP monitoring. METHODS: Patients with a new-onset
      RVO or DR that led to vitreous hemorrhage after a period of quiescence were
      identified. Informed consent was obtained, and patients were enrolled in the
      study if they met all of the inclusion criteria. Hypertension cut-offs were
      established in accordance with the Canadian Hypertension Education Program and
      the American Heart Association recommendations. All patients underwent a baseline
      BP measurement and 24-hour ambulatory BP monitoring. RESULTS: A total of 20
      patients were enrolled in the study. Eleven (55%) were female (mean age 67.5
      years). Seven patients (35%) had diabetes. Seventeen had retinal vein occlusions
      (85%), and 3 had sudden-onset activity in otherwise quiescent diabetic
      retinopathy (15%). Ten patients (50%) had no previous history of hypertension,
      and 10 (50%) had controlled hypertension on medications. Two patients (10%)
      failed to wear their BP cuff for the 24-hour duration and were excluded from the
      analysis. The average baseline systolic BP and diastolic BP were 133 and 78 mm
      Hg, respectively. Twelve patients (67%) tested positive for hypertension on their
      24-hour recording, and 5 (42%) of these patients had no history of hypertension.
      One of 12 patients (8%) had a positive nighttime average only but a normal
      daytime average. Nine of the 12 patients (75%) who had a positive recording had a
      subsequent change made to their medications. CONCLUSIONS: Uncontrolled
      hypertension is a known risk factor for the development of RVO and for vitreous
      hemorrhage in otherwise quiescent DR. Many of these patients may have occult
      hypertension that has not been detected by the currently usual standard. Twenty
      four-hour ambulatory BP monitoring is a useful and potentially lifesaving
      clinical test, which can detect uncontrolled hypertension, especially nocturnal
      hypertension, in this cohort of patients. The results of this test have important
      treatment implications that can help prevent or minimize further systemic
      complications.

PMID- 28457297
TI  - Formalin: a Formaldehyde Analogue.

PMID- 28457298
TI  - Formalin: a formaldehyde analogue.

PMID- 28457299
TI  - A case of bilateral eyelid histoplasmosis mistaken as basal cell carcinoma.

PMID- 28457300
TI  - Applanation tonometer disinfection: a national benchmarking study.

PMID- 28457301
TI  - Periorbital complex regional pain syndrome.

PMID- 28457302
TI  - Fundus autofluorescence in the buried optic disc drusen: optical coherence
      tomography findings.

PMID- 28457304
TI  - Doxycycline injection in orbital cyst associated to microphthalmos.

PMID- 28457303
TI  - Perioperative nonarteritic anterior ischemic optic neuropathy in Jehovah's
      Witnesses.

PMID- 28457305
TI  - Metastatic cervical adenocarcinoma to the orbital subperiosteal space.

PMID- 28457307
TI  - Ischemic central retinal vein occlusion in a 14-year-old female.

PMID- 28457306
TI  - Eyelid pilomatrixoma masquerading as chalazion.

PMID- 28457308
TI  - Optical coherence tomography and autofluoresceingraphy changes in solar
      retinopathy.

PMID- 28457309
TI  - Ocular injuries secondary to alexandrite laser-assisted hair removal.
AB  - PURPOSE: The aim of this study was to describe the clinical manifestations and
      outcomes of 4 patients who had sustained eye injury during alexandrite laser
      assisted hair removal. METHODS: This was a retrospective case series of 4
      patients who presented to 2 tertiary eye care hospitals over 2 years. Data on
      ophthalmic examination, spectral domain optical coherence tomography (Heidelberg
      Engineering, Heidelberg, Germany), and fundus fluorescein angiography were
      collected. RESULTS: Four female patients sustained injuries during alexandrite
      laser hair removal. One patient presented with acute anterior uveitis, 2 patients
      with subfoveal choroidal neovascularization, and 1 patient with intraretinal
      foveal hemorrhage. Visual acuity at last follow-up (range 3-6 months) was 20/15
      to 20/20. CONCLUSIONS: Ocular injuries can occur as a result of incorrect use of
      laser-assisted hair removal devices. Ophthalmologists should be aware of ocular
      damage caused by these devices.

PMID- 28457310
TI  - Unilateral choroidal detachment following the use of tamsulosin.

PMID- 28457311
TI  - A rare association: Cushing disease and central serous chorioretinopathy.

PMID- 28457312
TI  - Minocycline-induced hyperpigmentation of the skin, sclera, and palpebral
      conjunctiva.

PMID- 28457313
TI  - Late onset of persistent, deep stromal haze after corneal cross-linking in a
      patient with keratoconus.

PMID- 28457314
TI  - Protein-RNA: Structure function and recognition.

PMID- 28457315
TI  - Fluvastatin inhibits intimal hyperplasia in wild-type but not Thbs1-null mice.
AB  - BACKGROUND: Thrombospondin-1 (TSP-1) is functionally important to intimal
      hyperplasia (IH) development. Statin drugs have beneficial pleiotropic effects,
      including reduced IH; however, the effect of statins on IH in a TSP-1-independent
      setting is unknown. HYPOTHESIS: Statins will be less effective in attenuating IH
      after vascular injury in TSP-1-null (Thbs1-/-) mice compared with wild-type (WT)
      mice. MATERIALS AND METHODS: Carotid artery ligation was performed on WT and
      Thbs1-/- mice. Each strain was divided into two groups: no statin control or
      standard chow containing fluvastatin (10 or 40 mg/kg/d). After 28 d, analysis
      included morphometric analysis and real-time quantitative reverse transcription
      polymerase chain reaction on the arteries and enzyme-linked immunosorbent assay
      on plasma (TSP-1 WT, TSP-2 WT, and Thbs1-/-). Comparisons were made by analysis
      of variance, with P < 0.05 considered significant. RESULTS: In no statin
      controls, WT mice had more IH than Thbs1-/- mice (0.46 +/- 0.09 versus 0.15 +/-
      0.04). Fluvastatin reduced IH in the WT (0.46 +/- 0.09 versus 0.23 +/- 0.06), but
      not in Thbs1-/- groups (0.15 +/- 0.04 versus 0.22 +/- 0.07). No difference in IH
      existed between Thbs1-/- no statin controls and fluvastatin WT and Thbs1-/-
      groups. Statin dose did not affect IH. TSP-1 plasma levels were increased in
      fluvastatin WT. TSP-2 levels were decreased in fluvastatin WT and elevated in
      fluvastatin Thbs1-/-. Fluvastatin had no effect on tissue Thbs1 or Thbs2 gene
      expression. CONCLUSIONS: TSP-1 is necessary for robust IH after arterial injury.
      Because fluvastatin had no effect on IH in Thbs1-/-, the data suggest that the
      statin effect on IH may be largely TSP-1 dependent. Both statins and the presence
      of TSP-1 affect TSP-1 and TSP-2 plasma levels.

PMID- 28457317
TI  - Development of a critical-sized ventral hernia model in the pig.
AB  - BACKGROUND: The pig is commonly used as a preclinical model for ventral hernia
      repair. However, no study has verified that an unrepaired surgically induced
      hernia (control) in the pig does not heal spontaneously but rather develops a
      persistent hernia. Without such verification in any given model, one cannot draw
      conclusions on the efficacy of the repair technique investigated. MATERIALS AND
      METHODS: Three surgically induced hernia models with increasing severity were
      created in eight pigs. These included 10-cm retrorectus partial-thickness (model
      1) and 15-cm preperitoneal full-thickness (model 2) incisional defects and an 8 *
      8 cm preperitoneal full-thickness excisional defect (model 3). Postoperative
      management included use of an abdominal binder, and in some cases, suction
      drainage, for 2 wk to support the repair and prevent seroma. Models were
      evaluated for persistence of hernia at 5 wk using clinical and radiographic
      assessments. RESULTS: All pigs developed clinical hernias after 2 wk of defect
      creation, but only models 1 and 3 had clinically persistent hernias at 5 wk. At 5
      wk, the average defect area was 97 cm2 in model 1, 66 cm2 in model 2, and 245 cm2
      in model 3. Dense fibrotic scarring was observed in the models with resolved
      hernias. CONCLUSIONS: Our results highlight the need to verify an unrepaired
      hernia injury model does not heal spontaneously prior to using it for hernia
      repair studies. The partial-thickness incisional model 1 and full-thickness
      excisional model 3 formed persistent hernias in pigs at 5 wk and should be
      further explored as models for investigating hernia repair strategies.

PMID- 28457316
TI  - Emergent laparotomy and temporary abdominal closure for the cirrhotic patient.
AB  - BACKGROUND: Temporary abdominal closure (TAC) may be performed for cirrhotic
      patients undergoing emergent laparotomy. The effects of cirrhosis on physiologic
      parameters, resuscitation requirements, and outcomes following TAC are unknown.
      We hypothesized that cirrhotic TAC patients would have different resuscitation
      requirements and worse outcomes than noncirrhotic patients. METHODS: We performed
      a 3-year retrospective cohort analysis of 231 patients managed with TAC following
      emergent laparotomy for sepsis, trauma, or abdominal compartment syndrome. All
      patients were initially managed with negative pressure wound therapy (NPWT) TAC
      with intention for planned relaparotomy and sequential abdominal closure attempts
      at 24- to 48-h intervals. RESULTS: At presentation, cirrhotic patients had higher
      incidence of acidosis (33% versus 17%) and coagulopathy (87% versus 54%) than
      noncirrhotic patients. Forty-eight hours after presentation, cirrhotic patients
      had a persistently higher incidence of coagulopathy (77% versus 44%) despite
      receiving more fresh frozen plasma (10.8 units versus 4.4 units). Cirrhotic
      patients had higher NPWT output (4427 mL versus 2375 mL) and developed higher
      vasopressor infusion rates (57% versus 29%). Cirrhotic patients had fewer
      intensive care unit-free days (2.3 versus 7.6 days) and higher rates of multiple
      organ failure (64% versus 34%), in-hospital mortality (67% versus 21%), and long
      term mortality (80% versus 34%) than noncirrhotic patients. CONCLUSIONS:
      Cirrhotic patients managed with TAC are susceptible to early acidosis, persistent
      coagulopathy, large NPWT fluid losses, prolonged vasopressor requirements,
      multiple organ failure, and early mortality. Future research should seek to
      determine whether TAC provides an advantage over primary fascial closure for
      cirrhotic patients undergoing emergency laparotomy.

PMID- 28457318
TI  - Predictors of change in omega-3 index with fish oil supplementation in peripheral
      artery disease.
AB  - BACKGROUND: The omega-3 index represents the red blood cell (RBC) content of two
      major long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid,
      and docosahexaenoic acid. We sought to determine factors associated with a
      favorable response to fish oil treatment and to characterize changes in RBC PUFAs
      associated with fish oil supplementation. METHODS: This study was a secondary
      analysis of the OMEGA-PAD I trial, a randomized, double-blinded, placebo
      controlled trial investigating short-duration, high-dose n-3 PUFA oral
      supplementation on endothelial function and inflammation in subjects with
      peripheral arterial disease. Patients with mild to severe claudication received
      either 4.4 g of fish oil providing 2.6 g of eicosapentaenoic acid and 1.8 g of
      docosahexaenoic acid daily (n = 40) or placebo capsules (n = 40) for 1 mo. The
      RBC fatty acid content was measured by gas chromatography and expressed as a
      percent of total fatty acids. The change in omega-3 index was calculated as the
      difference between pre- and post-supplementation in the fish oil and placebo
      groups. Univariate analysis identified predictors of change in omega-3 index,
      with these variables included in our multivariable model. RESULTS: In the fish
      oil group, there was an increase in the omega-3 index (5.1+/- 1.3% to 9.0+/-
      1.8%; P < 0.0001), whereas there was no change in the control group. Factors
      associated with a favorable response (i.e., greater than the median change of
      4.06%) included a lower body mass index and higher concentrations of low-density
      lipoproteins. Other demographic and/or lifestyle factors such as age, race, or
      smoking status were unrelated to the response. Oral n-3 PUFA supplementation also
      decreased the n-6 PUFA content in RBCs. CONCLUSIONS: Short-term, high-dose n-3
      PUFA supplementation increases the omega-3 index to a greater extent in patients
      with a lower body mass index and higher total and low-density lipoprotein
      cholesterol levels.

PMID- 28457319
TI  - Validation of a breast cancer nomogram to predict lymphedema in a Chinese
      population.
AB  - BACKGROUND: Upper arm lymphedema (LE) is a common complication after axillary
      lymph node dissection (ALND) in breast cancer patients. This retrospective cohort
      study aimed to validate a published nomogram to predict the risk of LE in the
      Chinese breast cancer patients. METHODS: A total of 409 breast cancer patients
      who underwent breast cancer surgery and ALND (level I and II) were identified.
      Cox regression analysis was used to identify the risk factors for LE. The
      nomogram predictive of LE of breast cancer was evaluated by receiver-operating
      curve analysis, calibration plots, and Kaplan-Meier analysis in our study
      population. RESULTS: With a median follow-up of 68 months, the 5-year cumulative
      incidence of LE was 22.3%. Higher body mass index (hazard ratio [HR] = 1.06, 95%
      CI: 1.00-1.13), neoadjuvant chemotherapy (HR = 3.76, 95% CI: 2.29-6.20), larger
      extend of axillary surgery (level I/II/III versus level I/II: HR = 2.39, 95% CI:
      1.30-4.37), and radiotherapy (HR = 4.90, 95% CI: 1.90-12.5) were independently
      associated with LE. The AUC value of the nomogram was 0.706 (95% CI: 0.648
      0.752). A high-risk subgroup of patients defined by nomogram had significantly
      higher cumulative risk of LE than those in the low-risk subgroups (P < 0.01). The
      calibration plots revealed that the nomogram was well calibrated (Hosmer-Lemeshow
      test, P = 0.0634). CONCLUSIONS: The nomogram to predict the risk of LE in breast
      cancer patients with ALND has been validated to be discriminative and accurate.
      More studies are needed to evaluate the impact of other factors (lifestyle,
      behaviors, and so forth) on the performance of the nomogram.

PMID- 28457320
TI  - Surgical and trauma care in low- and middle-income countries: a review of
      capacity assessments.
AB  - BACKGROUND: Surgical and trauma capacity assessments help guide resource
      allocation and plan interventions to improve care for the injured in low- and
      middle-income countries (LMICs). To forge expert consensus on conducting these
      assessments, we undertook a systematic review of studies using five tools: (1)
      World Health Organization's (WHO) Guidelines for Essential Trauma Care, (2) WHO's
      Tool for Situational Analysis to Assess Emergency and Essential Surgical Care,
      (3) Personnel, Infrastructure, Procedures, Equipment, and Supplies tool, (4)
      Harvard Humanitarian Initiative tool, and (5) Emergency and Critical Care tool.
      MATERIALS AND METHODS: Publications describing utilization of survey instruments
      to assess surgical or trauma capacity in LMICs were reviewed. Included articles
      underwent thematic analysis to develop recommendations. A modified Delphi method
      was used to establish expert consensus. Experts rated recommendations on a Likert
      type scale via online survey. Consensus was defined by Cronbach's alpha >= 0.80.
      Recommendations achieving agreement by >=80% of experts were included. RESULTS:
      Two hundred and ninety-eight publications were identified and 41 included,
      describing evaluation of 1170 facilities across 36 LMICs. Nine recommendations
      were agreed upon by expert consensus: (1) inclusion of district hospitals, (2)
      inclusion of highest level public hospital, (3) inclusion of private facilities,
      (4) facility visits for on-site completion, (5) direct inspections, (6) checking
      surgical logs, (7) adaptation of survey instrument, (8) repeat assessments, and
      (9) need for increased collaboration. CONCLUSIONS: Expert recommendations
      developed in this review describe methodology to be employed when conducting
      assessments of surgical and trauma capacity in LMICs. Consensus has yet to be
      achieved for tool selection.

PMID- 28457322
TI  - Marriage and mortality after noncardiac surgery.
AB  - BACKGROUND: Marriage is linked to substantial societal and economic benefits, and
      it has been associated with improved outcomes following acute illness. However,
      it is not known if being married confers benefit to patients undergoing
      noncardiac surgical procedures. MATERIALS AND METHODS: Patients undergoing any
      noncardiac surgical procedure were included over a period of 19 months. All-cause
      mortality at 2 years was determined by linking patient records to the National
      Death Index. Risk adjustment was performed using Cox modeling and the Cleveland
      Clinic risk stratification index. RESULTS: Of the 11,588 patients included, 7830
      (68.0%) were married at the time of surgery. There was a significant interaction
      between sex and marital status (P = 0.03), so the remainder of the analysis was
      performed separately by sex. Among men, not being married was associated with
      significantly worse survival (hazard ratio [HR]: 1.31, 95% confidence interval
      [CI]: 1.06, 1.63), whereas among women, there was no significant association
      between marital status and survival (HR: 0.94, 95% CI: 0.77, 1.15). Furthermore,
      divorced men (HR: 1.76, 95% CI: 1.25, 2.51) and never married men (HR: 1.53, 95%
      CI: 1.14, 2.05) had significantly worse survival than married men, whereas there
      was no significant difference between widowed men and married men, nor when
      comparing widowed, divorced, or never married women to married women.
      CONCLUSIONS: Among a diverse group of surgical patients, being married at the
      time of surgery is associated with significantly improved survival only among
      men. Focused efforts to improve social support for unmarried male patients may
      improve outcomes.

PMID- 28457321
TI  - Effects of trauma, hemorrhagic shock, and chronic stress on lung vascular
      endothelial growth factor.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1
      and VEGFR-2) regulate vascular permeability and endothelial cell survival. We
      hypothesized that hemorrhagic shock (HS) and chronic stress (CS) would increase
      expression of lung VEGF and its receptors, potentiating pulmonary edema in lung
      tissue. MATERIALS AND METHODS: Male Sprague-Dawley rats aged 8-9 wk were
      randomized: naive control, lung contusion (LC), LC followed by HS (LCHS), and
      LCHS with CS in a restraint cylinder for 2 h/d (LCHS/CS). Animals were sacrificed
      on days 1 and 7. Expressions of lung VEGF, VEGFR-1, and VEGFR-2 were determined
      by polymerase chain reaction. Lung Injury Score (LIS) was graded on light
      microscopy by inflammatory cell counts, interstitial edema, pulmonary edema, and
      alveolar integrity (range: 0 = normal; 8 = severe injury). RESULTS: Seven days
      after LC, lung VEGF and VEGFR-1 were increased, and lung tissue healed (LIS: 0.8
      +/- 0.8). However, 7 d after LCHS and LCHS/CS, lung VEGF and VEGFR-1 expressions
      were decreased. VEGFR-2 was also decreased after LCHS/CS. LIS was elevated 7 d
      after LCHS and LCHS/CS (6.5 +/- 1.0 and 8.2 +/- 0.8). Increased LIS after LCHS
      and LCHS/CS was because of higher inflammatory cell counts, increased
      interstitial edema, and loss of alveolar integrity, whereas pulmonary edema was
      unchanged. CONCLUSIONS: Elevation of lung VEGF and VEGFR-1 expressions after LC
      alone was associated with healing of injured lung tissue. Expressions of VEGF,
      VEGFR-1, and VEGFR-2 were reduced after LCHS and LCHS/CS, and injured lung tissue
      did not heal. Persistent lung injury after severe trauma was because of
      inflammation rather than pulmonary edema.

PMID- 28457323
TI  - Lymphoepithelioma-like gastric carcinoma: clinicopathological characteristics and
      infection status.
AB  - BACKGROUND: Lymphoepithelioma-like gastric carcinoma (LLGC) is a rare subtype of
      gastric carcinoma (GC) characterized by prominent lymphocytic infiltration. LLGC
      may be associated with latent Epstein-Barr virus (EBV) infection or
      microsatellite instability (MSI). This study aims to assess the
      clinicopathological characteristics, EBV infection, and MSI status in LLGC.
      METHODS: A retrospective analysis of GC patients submitted to potentially
      curative resection between 2009 and 2014 was performed. The LLGC subtype
      specimens were examined for EBV by in situ hybridization and MSI by
      immunohistochemical analysis. The LLGC profile was analyzed accordingly to
      clinicopathological parameters. RESULTS: From 255 patients, seven were identified
      on the pathological report as LLGC. Six cases were EBV-positive and one had MSI,
      showing loss of MLH1 and PMS2 expression. LLGC was more frequently seen in men,
      and the mean age was 69 years. When compared to non-LLGC, LLGC cases were larger
      (~5.8 cm) poorly differentiated tumors and had lower incidence of lymph node
      metastasis (P = 0.045). Mean number of lymph nodes dissected in the LLGC group
      was 39.5, and only one patient had a single positive lymph node. In addition, two
      patients presented associated lesions. LLGC was not associated with HER-2,
      chromogranin and synaptophysin positivity or Helicobacter pylori infection.
      CONCLUSIONS: Distinct pathological aspects and clinical behavior of LLGC
      reinforce the need for proper recognition of this histological subtype to choose
      better therapeutic approaches.

PMID- 28457324
TI  - Liver autotransplantation and retrohepatic vena cava reconstruction for alveolar
      echinococcosis.
AB  - BACKGROUND: Alveolar echinococcosis (AE) is characterized by a slow-growing
      infiltrative neoplasm that is often unresectable by traditional methods because
      of strong adhesions and invasion to adjacent structures. We present our
      experience with liver autotransplantation and retrohepatic inferior vena cava
      (RHIVC) reconstruction using autogenous veins in patients with this end-stage
      parasitic disease. METHODS: Twelve patients with hepatic AE and extensive RHIVC,
      hepatic vein, and/or hilar invasion underwent ex vivo liver resection and RHIVC
      reconstruction using autogenous veins followed by autotransplantation in the West
      China Hospital of Sichuan University from 2013 to 2016. RESULTS: The mean weight
      of the harvested liver graft was 537 g (range: 390-900 g), the mean anhepatic
      time was 216 min (range, 120-310 min), and the mean operation time was 13.6 h
      (range, 10.5-19.5 h). The main postoperative complication was bile leakage. The
      mean postoperative hospital stay was 16.4 d (range, 10.0-37.0 d), and the median
      follow-up time was 15.5 mo (range, 1.0-32.0 mo). All patients were alive at the
      latest follow-up. The vascular patency rate was 100%, and no residual disease,
      recurrence, or metastasis was detected. CONCLUSIONS: To our knowledge, liver
      autotransplantation and RHIVC reconstruction using autogenous veins are rarely
      performed for patients with end-stage hepatic AE. This technique requires no
      organ donor, allogeneic, or artificial vessel implantation, postoperative
      immunosuppressive therapy, or long-term postoperative anticoagulant treatment.
      These benefits may make the treatment of select end-stage hepatic AE patients
      more affordable and effective.

PMID- 28457325
TI  - Physician preference and patient satisfaction with radioactive seed versus wire
      localization.
AB  - BACKGROUND: Nonpalpable breast lesions require localization before excision. This
      is most commonly performed with a wire (WL) or a radioactive seed (SL), which is
      placed into the breast under radiographic guidance. Although there are advantages
      of each modality, there are no guidelines to address which patients should
      undergo WL versus SL. We investigated factors influencing the selection of SL
      versus WL at our institution and assessed patient satisfaction with each
      procedure. METHODS: Patients undergoing preoperative localization of nonpalpable
      breast lesions from May 2014 through August 2015 were included. Physicians were
      surveyed on surgical scheduling to evaluate factors influencing the decision to
      perform SL or WL. Patient satisfaction was evaluated with a survey at the first
      postoperative visit. Retrospective chart review was performed. RESULTS: 341
      patients were included: 104 (30%) patients underwent SL and 237 (70%) underwent
      WL. There was no difference in patient age, benign versus malignant disease, or
      need for concomitant axillary surgery comparing the SL versus WL groups.
      Physician survey indicated that 18% of patients were candidates for WL only. Of
      the patients who were eligible for both, 88 (41%) ultimately underwent SL and 126
      (59%) had WL. The most commonly cited reason for selection of one localization
      method or the other was physician preference, followed by patient preference or
      avoiding additional visit. There was no significant difference in self-reported
      preoperative anxiety level, convenience of the localization procedure, pain of
      the localization procedure, operative experience, postoperative pain level or
      medication requirement, or overall patient satisfaction comparing patients who
      underwent SL and WL. CONCLUSIONS: SL and WL offer patients similar comfort and
      satisfaction. Factors influencing selection of one modality over the other
      include both logistic and clinical considerations.

PMID- 28457326
TI  - Breast cancer cells form primary tumors on ex vivo four-dimensional lung model.
AB  - BACKGROUND: Breast cancer mortality is most common in cancer in women, and there
      are no ex vivo models that can capture the primary growth of tumor with fidelity
      to the in vivo tumor growth. In this study, we grew human breast cancer cell
      lines in an acellular lung matrix of the ex vivo four-dimensional lung model to
      determine if they form primary tumor and the extent to which they mimic the
      histology and characteristics of the human tumors. MATERIALS AND METHODS: Rat
      lungs were harvested, decellularized, and placed in a bioreactor. To study the
      primary tumor growth, we seeded the lung via the trachea with human breast cancer
      cells SUM159, MCF7, or MDMB231 and perfused the pulmonary artery with oxygenated
      media. Lobectomies were performed and processed for hematoxylin and eosin, Ki-67,
      caspase-3, estrogen receptor, and progesterone receptor antibodies. RESULTS: All
      three cell lines grew in the ex vivo four-dimensional model and formed perfusable
      tumor nodules with similar histology and morphology as the primary tumors. SUM159
      and MDAMB231 showed higher proliferation and apoptotic indices than MCF7. In
      addition, MCF7 retained its estrogen receptor and progesterone receptor
      positivity, whereas SUM159 and MDAMB 231 did not have any staining. CONCLUSIONS:
      Overall, our study showed that human breast cancer cells can be grown on the ex
      vivo four-dimensional lung model, which then form primary tumor nodules that
      mimic the morphology and histology of the original tumor.

PMID- 28457327
TI  - An epidemiologic overview of 13 years of firearm hospitalizations in
      Pennsylvania.
AB  - BACKGROUND: Gun violence is a controversial public health issue plagued by a lack
      of recent research. We sought to provide a 13-y overview of firearm
      hospitalizations in Pennsylvania, analyzing trends in mode, intent, and outcome.
      We hypothesized that no adjusted change in mortality or functional status at
      discharge (FSD) would be observed for gunshot wound (GSW) victims over the study
      period. METHODS: All admissions to the Pennsylvania Trauma Outcome Study database
      from 2003 to 2015 were queried. GSWs were identified by external cause-of-injury
      codes. Collected variables included patient demographics, firearm type, intent
      (assault and attempted suicide), FSD, and mortality. Multilevel mixed-effects
      logistic regression models and ordinal regression analyses using generalized
      linear mixed models assessed the impact of admission year (continuous) on
      adjusted mortality and FSD score, respectively. Significance was set at P < 0.05.
      RESULTS: Of the 462,081 patients presenting to Pennsylvania trauma centers from
      2003 to 2015, 19,342 were GSWs (4.2%). Handguns were the most common weapon of
      injury (n = 7007; 86.7%) among cases with specified firearm type. Most GSWs were
      coded as assaults (n = 15,415; 79.7%), with suicide attempts accounting 1866
      hospitalizations (9.2%). Suicide attempts were most prevalent among young and
      middle-aged white males, whereas assaults were more common in young black males.
      Rates of firearm hospitalizations decreased over time (test of trend P = 0.001);
      however, admission year was not associated with improved adjusted survival
      (adjusted odds ratio: 0.99, 95% confidence interval: 0.97-1.01; P = 0.353) or FSD
      (adjusted odds ratio: 0.99, 95% confidence interval: 0.98-1.00; P = 0.089) while
      controlling for demographic and injury severity covariates. CONCLUSIONS: Temporal
      trends in outcomes suggest rates of firearm hospitalizations are declining in
      Pennsylvania; however, outcomes remain unchanged. To combat this epidemic, a
      multidisciplinary, demographic-specific approach to prevention should be the
      focus of future scientific pursuits.

PMID- 28457328
TI  - The ideal porcine model for major liver resection.

PMID- 28457330
TI  - Ileostomy creation in colorectal cancer surgery: risk of acute kidney injury and
      chronic kidney disease.
AB  - BACKGROUND: Ileostomy creation is associated with postoperative dehydration and
      readmission; however, the effect on renal function is unknown. Our goal was to
      characterize the impact of ileostomy creation on acute and chronic renal
      function. MATERIALS AND METHODS: A retrospective cohort study with patients
      undergoing colorectal cancer surgery at a tertiary referral institution (2005
      2011). The relationship between ileostomy creation and acute kidney injury (AKI)
      related readmission, severe chronic kidney disease (CKD) at 12 mo (glomerular
      filtration rate <30 mL/min/1.73 m2), and onset of severe CKD over time was
      evaluated using multivariable logistic and Cox regression and adjusted using
      propensity score stratification. RESULTS: Among 619 patients, 84 (13%) had
      ileostomy. AKI-related readmission and severe CKD at 12 mo were more common among
      ileostomy patients (17% versus 2%, P < 0.01 and 13.3% versus 5%, P = 0.02,
      respectively). After propensity score adjustment, ileostomy was a significant
      predictor of AKI-related readmissions (odds ratio: 10.3; 95% confidence interval
      [CI], 3.9-27.2), severe CKD at 12 mo (odds ratio: 4.1; 95% CI, 1.4-11.9), and
      onset of severe CKD over time (hazard ratio: 4.2; 95% CI, 2.3-6.6). CONCLUSIONS:
      Ileostomy creation is associated with increased risk of AKI-related readmissions
      and development of severe CKD. Future studies must focus on strategies to
      minimize kidney injury when ileostomy is a necessary component of colorectal
      cancer surgery and revisiting current indications for ileostomy creation.

PMID- 28457329
TI  - Physiological and Operative Severity Score for the enUmeration of Mortality and
      morbidity and modified Physiological and Operative Severity Score for the
      enUmeration of Mortality and morbidity for the mortality prediction among
      nonagenarians undergoing emergency surgery.
AB  - BACKGROUND: The aims of this study were to determine the outcomes of emergency
      abdominal surgery in patients aged >=90 y and to analyze the role of
      Physiological and Operative Severity Score for the enUmeration of Mortality and
      morbidity (POSSUM) and modified POSSUM in predicting their morbidity and
      mortality. MATERIALS AND METHODS: Patients aged >=90 y who underwent emergency
      abdominal surgery from January 2011 to December 2014 were enrolled in this study.
      RESULTS: A total of 36 patients satisfied the inclusion criteria. The mortality
      and morbidity rates in the study group were 8.3% and 61.1%, respectively. Overall
      observed-to-expected morbidity ratio calculated by POSSUM and modified POSSUM
      were 0.83 (chi2 = 32.189, P = 0.6045) and 0.97 (chi2 = 33.915, P = 0.7398),
      respectively. Both models demonstrated a good fit for prediction of morbidity.
      Overall observed-to-expected mortality ratios calculated by POSSUM and modified
      POSSUM were 0.26 (chi2 = 12.217, P = 0.2013) and 0.20 (chi2 = 12.217, P =
      0.0936), respectively. CONCLUSIONS: Both POSSUM and modified POSSUM accurately
      predicted morbidity in the setting of emergency abdominal surgery in
      nonagenarians.

PMID- 28457331
TI  - Beneficial effects of novel cross-linked hemoglobin YQ23 on hemorrhagic shock in
      rats and pigs.
AB  - BACKGROUND: To overcome the problems of previously reported hemoglobin-based
      oxygen carriers, we developed a stabilized nonpolymeric cross-linked tetrameric
      hemoglobin solution (YQ23). The aims of this study were to investigate the oxygen
      carrying and releasing properties of this novel hemoglobin-based oxygen carrier
      and to determine whether it has beneficial effects for hemorrhagic shock.
      METHODS: Using a hemorrhagic shock model in Sprague-Dawley rats and mini-pigs, we
      tested the effects of infusing 0.1, 0.3, and 0.5 g/kg YQ23 on animal survival,
      tissue oxygen delivery (DO2) and consumption (VO2), hemodynamics parameters, and
      liver, renal, and cardiac function. RESULTS: YQ23 infusion increased the survival
      rate of rats and pigs with severe hemorrhagic shock in a dose-dependent manner.
      Moreover, it improved the hemodynamic parameters, cardiac output, DO2 and VO2,
      and the mitochondrial respiratory function of vital organs. Among the three doses
      of YQ23, 0.5 gHb/kg YQ23 achieved a similar beneficial effect as whole blood.
      CONCLUSIONS: This study indicated that the novel cross-linked tetrameric
      hemoglobin YQ23 has good oxygen carrying and releasing properties and exhibits
      beneficial effects on hemorrhagic shock in rats and pigs by improving the oxygen
      carrying and delivery function of blood, which maintains organ function.

PMID- 28457333
TI  - Computerized tomography-based anatomic description of the porcine liver.
AB  - BACKGROUND: The knowledge of the anatomic features is imperative for successful
      modeling of the different surgical situations. This study aims to describe the
      anatomic features of the porcine using computerized tomography (CT) scan.
      METHODS: Thirty large, white, female pigs were included in this study. The CT
      image acquisition was performed in four-phase contrast study. Subsequently,
      analysis of the images was performed using syngo.via software (Siemens) to
      subtract mainly the hepatic artery and its branches. Analysis of the portal and
      hepatic veins division pattern was performed using the Myrian XP-Liver 1.14.1
      software (Intrasense). RESULTS: The mean total liver volume was 915 +/- 159 mL.
      The largest sector in the liver was the right medial one representing around 28
      +/- 5.7% of the total liver volume. Next in order is the right lateral sector
      constituting around 24 +/- 5%. Its volume is very close to the volume of the left
      medial sector, which represents around 22 +/- 4.7% of the total liver volume. The
      caudate lobe represents around 8 +/- 2% of the total liver volume.The portal vein
      did not show distinct right and left divisions rather than consecutive branches
      that come off the main trunk. The hepatic artery frequently trifurcates into left
      trunk that gives off the right gastric artery and the artery to the left lateral
      sector, the middle hepatic artery that supplies both the right and the left
      medial sectors and the right hepatic artery trunk that divides to give anterior
      branch to the right lateral lobe, branch to the right medial lobe, and at least a
      branch to the caudate lobe. Frequently, there is a posterior branch that crosses
      behind the portal vein to the right lateral lobe. The suprahepatic veins join the
      inferior vena cava in three distinct openings. There are communications between
      the suprahepatic veins that drain the adjacent sectors. The vein from the right
      lateral and the right medial sectors drains into a common trunk. The vein from
      the left lateral and from the left medial sectors drains into a common trunk. A
      separate opening is usually encountered draining the right medial sector. The
      caudate lobe drains separately into inferior vena cava caudal to the other veins.
      CONCLUSIONS: Knowledge of the anatomic features of the porcine liver is crucial
      to the performance of a successful surgical procedure. We herein describe the CT
      depicted anatomic features of the porcine liver.

PMID- 28457332
TI  - Comparison between minimally invasive and open surgical treatment in necrotizing
      pancreatitis.
AB  - BACKGROUND: Minimal access techniques have gained popularity for the management
      of necrotizing pancreatitis, but only a few studies compared open necrosectomy
      with a less invasive treatment. The aim of this study was to evaluate the
      outcomes of minimally invasive treatment for necrotizing pancreatitis in
      comparison with open necrosectomy. MATERIALS AND METHODS: This retrospective
      study included 70 patients who underwent minimally invasive intervention or open
      surgical debridement for necrotizing pancreatitis between January 2007 and
      December 2014. Data were analyzed for postoperative morbidity and outcome.
      RESULTS: Of 70 patients, 22 patients underwent primary open necrosectomy and 48
      patients were treated with minimally invasive techniques. Percutaneous and
      endoscopic drainage were successful in 34.9% and 75.0% of patients, respectively.
      The rates of postoperative new-onset organ failure and intensive care unit stay
      were significantly lower in the minimally invasive group (25.0% versus 54.5%; P =
      0.016, and 29.2% versus 54.5%; P = 0.041, respectively). Gastrointestinal
      fistulas occurred more frequently after primary open necrosectomy (36.4% versus
      10.4%; P = 0.009). Mortality was comparable in both groups (18.6% versus 27.3%; P
      = 0.420). Mortality for salvage open necrosectomy was similar to that for primary
      open debridement (28.6% versus 27.3%; P = 0.924). The independent risk factors
      for major postoperative complications were primary open necrosectomy (P = 0.028)
      and shorter interval to first intervention (P = 0.020). Mortality was
      independently associated only with older age (P = 0.009). CONCLUSIONS: Minimally
      invasive treatment should be preferred over open necrosectomy for initial
      management of necrotizing pancreatitis.

PMID- 28457334
TI  - Plasma DNA and RNA differentially impact coagulation during abdominal sepsis-an
      explorative study.
AB  - BACKGROUND: Cell-free DNA (cfDNA) and extracellular RNA (exRNA) are both
      suspected to activate coagulation cascades in sepsis. Therefore, our study
      investigated the influence of plasmatic nucleic acids on coagulation in septic
      patients in comparison to patients after major abdominal surgery. MATERIALS AND
      METHODS: A total of 15 patients with sepsis, 10 postoperative patients, and 10
      healthy volunteers were included in this longitudinal study. Blood was collected
      at sepsis onset and after surgery respectively, as well as after 24, 72 and 168
      h. Levels of cfDNA and exRNA were measured by quantitative probe-based polymerase
      chain reaction. In addition, thromboelastography for coagulation as well as
      thromboaggregometry for platelet function was conducted. RESULTS: Both cfDNA and
      exRNA were elevated in patients with sepsis compared with postoperative patients
      and healthy volunteers. While higher exRNA levels correlated with a faster
      clotting time and more stable clots, cfDNA correlated with a shorter clotting
      time but also less fibrinolysis. In addition, higher cfDNA seems to be associated
      with kidney dysfunction as well as with general markers of cell damage (lactate
      dehydrogenase and lactate). CONCLUSIONS: Both nucleic acid species might be
      associated with different effects on coagulation during sepsis, with an overall
      procoagulatory influence. For this reason, individualized therapeutic approaches
      in patients suffering from coagulation-associated organ dysfunction might be
      feasible.

PMID- 28457335
TI  - Characterization of ventral incisional hernia and repair using shear wave
      elastography.
AB  - BACKGROUND: To assess the integrity of hernia repair, imaging modalities such as
      computed tomography or ultrasound (US) are commonly used. Neither modality has
      currently the capacity to simultaneously image the mesh and quantify a prosthetic
      and surrounding tissue stiffness. In this pilot study, we hypothesize that US
      shear wave elastography (SWE) can be used to identify a polyester mesh and a
      biologic graft and to assess their stiffness noninvasively in a rat model of
      bridging hernia repair. METHODS: Lewis rats underwent hernia creation and repair
      with Parietex or Strattice at 30 d. After 3 mo, the animals were euthanized, and
      the Young's Modulus was measured using SWE. Three-dimensional reconstructions of
      the hernia pre- and post-repair were performed using in-house image processing
      algorithms. RESULTS: SWE was capable of accurate and real-time assessment and
      diagnosis of the hernia defects in vivo. Young's Modulus of Parietex meshes and
      Strattice grafts as estimated from the shear wave elastograms were found to be
      statistically different from each other (P < 0.05). Accurate three-dimensional
      reconstructions of the hernia defects pre- and post-repair were generated.
      CONCLUSIONS: In this study, we demonstrate the feasibility of using US SWE to
      detect ventral hernias and evaluate mesh repair in vivo. Our results indicate
      that the presence of a hernia and repair can be reliably visualized by SWE and
      three dimensionally reconstructed. Thus, this technique may provide both
      structural and functional information regarding the hernia and the repair.

PMID- 28457336
TI  - Association of socioeconomics, surgical therapy, and survival of early stage
      hepatocellular carcinoma.
AB  - BACKGROUND: Underutilization of potential curative surgical treatment remains a
      problem in the management of hepatocellular carcinoma (HCC). Demographic and
      socioeconomic disparities continue to be important factors impacting utilization
      patterns, and exact mechanisms underlying these disparities remain largely
      unclarified. Focusing on these mechanisms provides us with a potential approach
      to improve survival of HCC patients. METHODS: We performed a retrospective cohort
      study using the Surveillance, Epidemiology, and End Results Database to assess
      patients with early stage HCC diagnosed between January 2004 and December 2012.
      Demographic and socioeconomic factors were analyzed to assess associations with
      utilization of treatment, stage of presentation, and disease-specific survival by
      means of multinominal and Cox regression. RESULTS: A total of 13,694 patients
      were included in the analysis of which only 6239 (45.6%) underwent surgical
      treatment for early stage HCC. Surgical treatment options consisted of 1445 liver
      resections (10.6%), 2121 liver transplantations (15.5%), and 2673 liver ablations
      (19.5%). The rate of surgical treatment fell from 56.1% in 2004 to 37.8% in 2012.
      Compared with no surgical therapy, African Americans were less likely to undergo
      liver transplantation (relative risk ratio [RRR] = 0.54; 95% confidence interval
      [CI], 0.36-0.79) than Caucasian patients and more likely to undergo surgical
      resection (RRR = 1.67; 95% CI, 1.13-2.48). Patients from the Pacific West were
      less likely to be transplanted versus patients from the Southeast (RRR = 0.68;
      95% CI, 0.50-0.93). Also, patients who were married (RRR = 2.44; 95% CI, 1.96
      3.04) or had health insurance (RRR = 4.74; 95% CI, 1.66-13.6) were more likely to
      receive liver transplantation. Young age (hazard ratio = 1.02; 95% CI, 1.00-1.03;
      P = 0.025) and positive marital status (hazard ratio = 0.71; 95% CI, 0.55-0.92; P
      = 0.010) both were independently associated with increased disease-specific
      survival. CONCLUSIONS: An increasing proportion of patients with early stage HCC
      did not undergo surgical therapy between 2004 and 2012. Demographic and
      socioeconomic factors were associated with different treatment modality
      utilization after controlling for available confounders. Of these factors, age
      and marital status were independently associated with increased disease-specific
      survival.

PMID- 28457337
TI  - C-reactive protein as early predictor of complications after minimally invasive
      colorectal resection.
AB  - BACKGROUND: Minimally invasive surgery (MIS) and enhanced recovery programs have
      been increasingly adopted in colorectal surgery. The aim of this prospective
      observational study was to evaluate the usefulness of the C-reactive protein
      (CRP) concentration measured on postoperative day 3 (POD-3) as an early predictor
      of severe complications after minimally invasive colorectal resection. MATERIALS
      AND METHODS: From January 2014 to December 2015, 160 patients underwent resection
      of colorectal disease by MIS at the Division of General and Hepatobiliary
      Surgery, University of Verona Hospital Trust. Among these, CRP measurement was
      available on POD-3 in 143 patients. RESULTS: Conversion from laparoscopic to open
      surgery was necessary in 18 patients (12.6%). The mean POD-3 CRP concentration
      was significantly higher in patients who did than did not require conversions
      (205.6 +/- 89.6 mg/L versus 104.6 +/- 85.8 mg/L, respectively; P < 0.001), even
      in the absence of postoperative complications, and these patients were therefore
      excluded from the subsequent analysis. No deaths occurred during the study
      period, but complications occurred in 39 patients (31.2%). Among these, 24
      patients (61.5%) developed surgery-related complications. A POD-3 CRP
      concentration of 120 mg/L was highly reliable for excluding the occurrence of
      surgery-related and severe complications. The negative predictive values for
      excluding surgery-related and severe complications was 86.8% and 97.7%,
      respectively. CONCLUSIONS: Assessment of the POD-3 CRP concentration after
      colorectal MIS is clinically significant for excluding the occurrence of surgery
      related and severe complications. This measurement is a largely available,
      inexpensive, and easy-to-use tool that allows early and safe discharge in the
      setting of colorectal MIS and enhanced recovery programs.

PMID- 28457338
TI  - Mammalian cell models to advance our understanding of wound healing: a review.
AB  - Rapid and efficient healing of damaged tissue is critical for the restoration of
      tissue function and avoidance of tissue defects. Many in vitro cell models have
      been described for wound healing studies; however, the mechanisms that underlie
      the process, especially in chronic or complicated wounds, are not fully
      understood. The identification of cell culture systems that closely simulate the
      physiology of damaged tissue in vivo is necessary. We describe the cell culture
      models that have enhanced our understanding, this far, of the wound healing
      process or have been used in drug discovery. Cell cultures derived from the
      epithelium, including corneal, renal, intestinal (IEC-8 cells and IEC-6), skin
      epithelial cells (keratinocytes, fibroblasts, and multipotent mesenchymal stem
      cells), and the endothelium (human umbilical vein endothelial cells, primary
      mouse endothelial cells, endodermal stem cells, human mesenchymal stem cells, and
      corneal endothelial cells) have played a pivotal role toward our understanding of
      the mechanisms of wound healing. More studies are necessary to develop co-culture
      cell models which closely simulate the environment of a wound in vivo. Cell
      culture models are invaluable tools to promote our understanding of the
      mechanisms that regulate the wound healing process and provide a platform for
      drug discovery.

PMID- 28457339
TI  - Optimal surgical technique in spontaneous pneumothorax: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Numerous thoracoscopic techniques have been used in the management of
      primary spontaneous pneumothorax (PSP), including wedge resection, pleurectomy,
      pleural abrasion, chemical pleurodesis, and staple line covering. The purpose of
      this systematic review was to compare outcomes for the most commonly reported
      techniques. MATERIALS AND METHODS: A systematic literature search looking at
      pneumothorax recurrence rate, length of stay, and chest tube duration after
      surgery was conducted in accordance with Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines using the PubMed database. RESULTS: Fifty
      one unique studies comprised of 6907 patients published between January 1988 and
      June 2015 were identified. Heterogeneity among effect sizes was significant for
      all outcomes. The lowest recurrence rates were observed in the wedge resection +
      chemical pleurodesis (1.7%; 95% confidence interval [CI], 1.0%-2.7%) and the
      wedge resection + pleural abrasion + chemical pleurodesis (2.8%; 95% CI, 1.7%
      4.7%) groups. The shortest chest tube duration and length of stay were observed
      in the wedge resection + staple line covering +/- other group (2.1 d; 95% CI, 1.4
      2.9 and 3.3 d; 95% CI, 2.6-4.0, respectively). CONCLUSIONS: The variability in
      reported outcomes and the lack of published multicenter randomized controlled
      trials highlights a need for more robust investigations into the optimal surgical
      technique in the management of PSP. Based on the limited quality studies
      available, this systematic review favors wedge resection + chemical pleurodesis
      and wedge resection + pleural abrasion + chemical pleurodesis in terms of
      recurrence rate after surgery for PSP.

PMID- 28457340
TI  - Immune and metabolic responses in early and late sepsis during mild dietary zinc
      restriction.
AB  - BACKGROUND: Mild dietary zinc (Zn) deficiency is widespread in human populations,
      but its influence on recovery after acute illness is poorly understood. In a
      mouse model of abdominal sepsis (cecal ligation puncture), systemic immune
      responses and liver metabolism were monitored in early (24 h) and late (5 d)
      phases, under control conditions and during mild dietary Zn restriction. METHODS:
      Mice were fed diets adequate or marginally deficient (ZM) in Zn (30 versus 10 mg
      zinc/kg diet) for 4 wk, before undergoing laparotomy alone (nonseptic control) or
      cecal ligation puncture (septic). RESULTS: Among nonseptic mice, the ZM state was
      not associated with differences in inflammation or metabolic responses. Among
      septic mice, mortality did not differ between the zinc adequate and ZM groups. In
      the early phase, the ZM state amplified increases in plasma interleukin (IL) 6,
      tumor necrosis factor alpha, and IL-10, while dampening the interferon gamma
      response. In the late phase, subtle but significant ZM-associated increases were
      observed in plasma IL-5 and interferon gamma levels and hepatic protein
      synthesis, the latter of which appeared to be mammalian target of rapamycin
      independent and was associated with increased hepatic tumor necrosis factor alpha
      messenger RNA content. CONCLUSIONS: Without increasing mortality, the ZM state is
      associated with a more disordered acute systemic inflammatory response and
      persistence or enhancement of acute phase responses within the liver parenchyma.

PMID- 28457341
TI  - Gender disparities in the utilization of laparoscopic groin hernia repair.
AB  - BACKGROUND: Clinical treatment guidelines have suggested that laparoscopic hernia
      repair should be the preferred approach in both men and women with bilateral or
      recurrent elective groin hernias. Anecdotal evidence suggests, however, that
      women are less likely to undergo a laparoscopic repair than men, and therefore,
      we aimed to delineate if these disparities persisted after controlling for
      patient factors and comorbidities. MATERIALS AND METHODS: The American College of
      Surgeons National Surgical Quality Improvement Project data were abstracted for
      all elective groin hernia repairs between 2005 and 2014. Univariate analysis was
      used to compare rates of laparoscopic surgery between men and women.
      Multivariable analysis was performed, controlling for patient demographics,
      preoperative comorbidities, and year of surgery. RESULTS: Over the 10-y period,
      141,490 patients underwent elective groin hernia repair, of which 13,325 were
      women (9.4%). The rate of general anesthesia utilization was high in both men
      (81.3%) and women (77.2%) with 75.1% of open repairs being performed under
      general anesthesia. Overall, 20.2% of women underwent laparoscopic repair
      compared with 28.0% of men (P < 0.01). Women tended to be older, had a lesser
      body mass index, and slightly greater American Anesthesia Association (all P <
      0.05). On multivariable regression, women had decreased odds of undergoing a
      laparoscopic approach compared with men (odds ratio: 0.70; 95% confidence
      interval, 0.67-0.73, P < 0.01). CONCLUSIONS: In the elective setting, women were
      less likely to undergo laparoscopic repair of groin hernias than men. Although we
      are unable to ascertain underlying causes for these gender disparities, these
      data suggest that there remains a disparity in the management of groin hernias in
      women.

PMID- 28457342
TI  - Outcome after coronary bypass grafting for coronary complications following
      coronary angiography.
AB  - BACKGROUND: Coronary complications during coronary angiography or intervention
      (percutaneous coronary intervention [PCI]) are uncommon. However, PCI-related
      coronary artery perforation, dissection, or acute occlusion frequently result in
      myocardial ischemia followed by hemodynamic instability and need of urgent
      coronary artery bypass grafting (coronary artery bypass grafting [CABG]). This
      single-center study aimed to investigate clinical outcomes of patients undergoing
      urgent CABG after life-threatening PCI complications. MATERIALS AND METHODS: Data
      were retrospectively obtained using our institutional patient database. All
      patients admitted for urgent CABG following PCI-related complications from April
      2010 to June 2015 were included into this study. Univariate analysis was
      performed to identify possible predictors for cardiac mortality. RESULTS: From a
      total of 821 urgent CABG patients, 52 patients (6.3%, 66.4 +/- 9.4 years)
      underwent CABG for coronary complication following PCI. Logistic EuroSCORE was
      21.8 +/- 15.0%. At admission, 22 of 52 (42%) presented in cardiogenic shock, and
      24 of 52 (46%) had significant electrocardiogram alterations indicating ST
      elevation myocardial infarction (STEMI). Surgical revascularization was performed
      by targeting the injured coronary vessel with additional revascularization of
      other compromised vessels as indicated (mean number of grafts 2.4 +/- 0.8). In
      hospital cardiac mortality of the patient cohort was 13.5% (7/52) with 15.4%
      (8/52) in-hospital all-cause mortality. Preoperative resuscitation, cardiogenic
      shock, and STEMI were predictors for in-hospital cardiac mortality (P < 0.05) in
      univariate analysis. In contrast, noncardiac comorbidities, type of PCI
      complication, and localization of the culprit lesion were not associated to
      increased mortality. CONCLUSIONS: Emergent or urgent CABG for treatment of acute
      coronary complications following PCI is feasible and has acceptable clinical
      results that worsen in the presence of STEMI, cardiogenic shock, or
      resuscitation. Because preoperative status is crucial for clinical outcomes in
      these patients, immediate transfer to cardiac surgery is necessary.

PMID- 28457343
TI  - Accumulation and cellular localization of nanoparticles in an ex vivo model of
      acute lung injury.
AB  - BACKGROUND: The benefit of nanomedicine in mitigating acute lung injury (ALI) is
      currently unknown. Therefore, we introduced the generation IV polyamidoamine
      dendrimers with neutral surface property (dendrimer) into our established ex vivo
      animal model and sought to determine their biodistribution to define their
      cellular uptake profile and to evaluate their potential as a drug delivery
      candidate for the treatment of ischemia-reperfusion-induced ALI. METHODS: Eight
      rabbit heart-lung blocks were harvested and exposed to 18 h of cold ischemia. The
      heart-lung blocks were then reperfused with rabbit donor blood. Dendrimer was
      conjugated to fluorescein isothiocyanate (D-FITC) for localization and
      quantification studies. D-FITC (30 mg or 150 mg) was injected into the bypass
      circuit and baseline, 1- and 2-h tissue samples were obtained to determine
      percent uptake. Low (10*) and high (40*) magnification images were obtained using
      confocal microscopy to confirm the accumulation and to determine the cellular
      targets of the dendrimer. RESULTS: Four heart-lung blocks were exposed to 30 mg
      and four to 150 mg of D-FITC. After adjusting for dry weight, the mean uptake in
      the 30 and 150 mg samples after 2 h of reperfusion were 0.79 +/- 0.16% and 0.39
      +/- 0.22% of perfused doses, respectively. Confocal imaging demonstrated
      dendrimer uptake in epithelial cells and macrophages. CONCLUSIONS: Fluorescently
      tagged dendrimers demonstrated injury-dependent tissue accumulation in a variety
      of different cell types. This unique approach will allow conjugation to and
      delivery of multiple agents with the potential of mitigating ALI injury while
      avoiding systemic toxicity.

PMID- 28457344
TI  - Prospective comparison of Sapylin and Avitene for reducing hydrops after axillary
      lymphadenectomy in breast cancer patients.
AB  - BACKGROUND: This study compared the efficacy of Sapylin and Avitene in reducing
      postoperative axillary seroma formation and effusion when applied topically after
      axillary lymphadenectomy. METHODS: A total of 224 patients were randomly divided
      into a Sapylin treatment group (STG), an Avitene treatment group, and a control
      group (CG). All patients underwent axillary lymphadenectomy and were treated
      during surgery with Sapylin, Avitene, or neither according to their group
      assignment. The duration and amount of postoperative drainage, as well as the
      occurrence of seromas were recorded. Outcomes were compared by one-way analysis
      of variance and chi-square tests. RESULTS: Baseline patient data, including age,
      body mass index, history of neoadjuvant chemotherapy, type of surgery, number of
      resected lymph nodes, and number of positive metastases did not differ among the
      three groups. Patients in both the STG and the Avitene treatment group
      experienced significantly fewer days of drainage than those in the CG; there was
      no significant difference in drainage tube retention time between the two treated
      groups. The STG experienced significantly less drainage volume than the CG. Fewer
      patients in both treatment groups required seroma treatment or experienced
      complications compared with CG patients. CONCLUSIONS: Both Sapylin and Avitene
      effectively reduced postoperative subcutaneous fluid accumulation after axillary
      lymphadenectomy. These treatments may be particularly useful for breast cancer
      patients at high risk of seroma formation, especially those with hypertension,
      diabetes mellitus, or a high body mass index who undergo axillary
      lymphadenectomy.

PMID- 28457345
TI  - Solving the negative impact of congestion in the postanesthesia care unit: a cost
      of opportunity analysis.
AB  - BACKGROUND: Congestion in the postanesthesia care unit (PACU) leads to the
      formation of waiting queues for patients being transferred after surgery,
      negatively affecting hospital resources. As patients recover in the operating
      room, incoming surgeries are delayed. The purpose of this study was to establish
      the impact of this phenomenon in multiple settings. METHODS: An operational
      mathematical study based on the queuing theory was performed. Average queue
      length, average queue waiting time, and daily queue waiting time were evaluated.
      Calculations were based on the mean patient daily flow, PACU length of stay,
      occupation, and current number of beds. Data was prospectively collected during a
      period of 2 months, and the entry and exit time was recorded for each patient
      taken to the PACU. Data was imputed in a computational model made with MS Excel.
      To account for data uncertainty, deterministic and probabilistic sensitivity
      analyses for all dependent variables were performed. RESULTS: With a mean patient
      daily flow of 40.3 and an average PACU length of stay of 4 hours, average total
      lost surgical opportunity time was estimated at 2.36 hours (95% CI: 0.36-4.74
      hours). Cost of opportunity was calculated at $1592 per lost hour. Sensitivity
      analysis showed that an increase of two beds is required to solve the queue
      formation. CONCLUSIONS: When congestion has a negative impact on cost of
      opportunity in the surgical setting, queuing analysis grants definitive actions
      to solve the problem, improving quality of service and resource utilization.

PMID- 28457346
TI  - A multi-institution analysis of general surgery resident peer-reviewed
      publication trends.
AB  - BACKGROUND: The process of taking a research project from conception to
      publication is one way to encourage surgeons to communicate hypothesis,
      critically assess literature and data, and defend research conclusions to a broad
      audience. The goal of this study was to define surgery resident publishing
      epidemiology and identify characteristics of residents and residency programs
      that might predict increased publication productivity. MATERIALS AND METHODS: A
      survey was administered to eight general surgery residency programs to collect
      residency and resident variables from 1993-2013. The primary endpoint was the
      number of first-author publications produced per resident. Secondary endpoints
      included clinical setting at which the former resident was practicing, fellowship
      pursued, and manuscript quality. RESULTS: Between 1993 and 2013, 676 residents
      graduated, median age was 33 years (range: 29-43 years) and 182 (27%) were
      female. Three hundred and sixty-six (54%) residents produced 1229 first-author
      publications. Of these, 112 (31%) residents produced one manuscript, 125 (34%)
      produced two-three manuscripts, 107 (29%) produced four-nine manuscripts, and 22
      (6%) produced 10 or more manuscripts. Publishing >=1 manuscript in residency was
      associated with a 1.5 (P = 0.01) increased odds of having attended a top-tier
      research institution for medical school and a 2.3 (P < 0.001) increased odds of
      having dedicated research years incorporated into residency. Surgeons practicing
      at academic centers had 1.7 (P = 0.003) greater odds of having attended top-tier
      medical schools, and 1.5 (P = 0.02) greater odds of publishing during residency.
      CONCLUSIONS: Additional research directed at identifying interventions promoting
      resident publishing and scholastic achievement should benefit all surgery
      training programs looking to cultivate the next generation of critically thinking
      surgeons.

PMID- 28457347
TI  - Thrombocytopenia and the outcomes of hepatectomy for hepatocellular carcinoma: a
      meta-analysis.
AB  - BACKGROUND: Recently, increasing studies have revealed the association of
      inflammatory parameters, such as preoperative platelet count, and the prognosis
      of hepatocellular carcinoma (HCC). However, the link between the platelet count
      and the prognosis of patients with HCC after hepatic resection is still
      controversial. METHODS: We searched PubMed, Web of Science, EMBASE, and CBM for
      relevant trials and analyzed outcomes with random-effects model. The hazard ratio
      (HR) and its 95% confidence interval (CI) were calculated. RESULTS: In total, 31
      studies, including a total of 10,730 patients, met our criteria. The results
      showed that thrombocytopenia in HCC patients was associated with poor overall
      survival (HR = 1.47, 95% CI: 1.21-1.78), disease-free survival (HR = 1.36, 95%
      CI: 1.08-1.72), and a high risk of cancer recurrence (HR = 1.41, 95% CI: 1.22
      1.62), but a low risk of extrahepatic metastasis (HR = 0.55, 95% CI: 0.47-0.63).
      CONCLUSIONS: The meta-analysis revealed that preoperative platelet count could
      act as a significant biomarker in the prognosis of HCC, especially a platelet
      count of <100 * 103/mm3. Additional high-quality trials are needed, considering
      the low-quality studies analyzed.

PMID- 28457348
TI  - West Nile Virus.

PMID- 28457349
TI  - Zika Virus.
AB  - The ongoing epidemic of Zika fever in the Western Hemisphere has drawn
      considerable attention from the medical and scientific communities as well as the
      general public, largely because of its association with birth defects and
      postinfectious sequelae. Since its appearance in Brazil in 2015, Zika virus has
      spread to more than 45 countries in the Western Hemisphere and has caused
      countless infections. To date, no treatment or vaccine exists, but a considerable
      multinational effort to halt Zika virus transmission is underway. This article
      reviews the basic biology, epidemiology, pathophysiology, diagnosis, and
      treatment of Zika virus and Zika fever.

PMID- 28457350
TI  - Ebola Virus Disease: An Update on Epidemiology, Symptoms, Laboratory Findings,
      Diagnostic Issues, and Infection Prevention and Control Issues for Laboratory
      Professionals.
AB  - The 2014 to 2016 Ebola virus disease (EVD), through the sheer size of the
      outbreak and combined experience within both resource-rich and resource-poor
      settings, allowed for more information to be gained about the clinical and
      pathologic features of EVD. This review highlights the range of aspects of EVD
      that the authors find are relevant to laboratory medicine, including the need for
      robust prediagnostic and laboratory processing algorithms to inform sampling of
      suspect patients, the vast majority of whom, in resource-rich settings, will have
      another diagnosis.

PMID- 28457353
TI  - Tick-Borne Emerging Infections: Ehrlichiosis and Anaplasmosis.
AB  - Human ehrlichiosis and anaplasmosis are acute febrile tick-borne infectious
      diseases caused by various members from the genera Ehrlichia and Anaplasma.
      Ehrlichia chaffeensis is the major etiologic agent of human monocytotropic
      ehrlichiosis (HME), while Anaplasma phagocytophilum is the major cause of human
      granulocytic anaplasmosis (HGA). The clinical manifestations of HME and HGA
      ranges from subclinical to potentially life-threatening diseases associated with
      multi-organ failure. Macrophages and neutrophils are the major target cells for
      Ehrlichia and Anaplasma, respectively. The threat to public health is increasing
      with newly emerging ehrlichial and anaplasma agents, yet vaccines for human
      ehrlichioses and anaplasmosis are not available, and therapeutic options are
      limited. This article reviews recent advances in the understanding of HME and
      HGA.

PMID- 28457351
TI  - Rift Valley Fever.
AB  - Rift Valley fever (RVF) is a severe veterinary disease of livestock that also
      causes moderate to severe illness in people. The life cycle of RVF is complex and
      involves mosquitoes, livestock, people, and the environment. RVF virus is
      transmitted from either mosquitoes or farm animals to humans, but is generally
      not transmitted from person to person. People can develop different diseases
      after infection, including febrile illness, ocular disease, hemorrhagic fever, or
      encephalitis. There is a significant risk for emergence of RVF into new
      locations, which would affect human health and livestock industries.

PMID- 28457354
TI  - Clostridium difficile.
AB  - Clostridium difficile infections (CDIs) have emerged as one of the principal
      threats to the health of hospitalized and immunocompromised patients. The
      importance of C difficile colonization is increasingly recognized not only as a
      source for false-positive clinical testing but also as a source of new infections
      within hospitals and other health care environments. In the last five years,
      several new treatment strategies that capitalize on the increasing understanding
      of the altered microbiome and host defenses in patients with CDI have completed
      clinical trials, including fecal microbiota transplantation. This article
      highlights the changing epidemiology, laboratory diagnostics, pathogenesis, and
      treatment of CDI.

PMID- 28457352
TI  - Carbapenem-Resistant Enterobacteriaceae.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a major threat.
      Commonly used antibiotics are generally inactive against CRE. Therefore, timely
      detection of CRE is of paramount importance. Among CRE, those producing
      carbapenem-hydrolyzing beta-lactamase enzymes (carbapenemase-producing
      Enterobacteriaceae) are particularly of concern because they tend to spread, and
      treatment is difficult. The carbapenemase groups most commonly encountered
      include KPC, NDM, and OXA-48. Treatment options are limited and include
      combinations of polymyxins, tigecycline, aminoglycosides, or carbapenems; newer
      agents with activity against CRE and better safety profiles are becoming
      available and will likely emerge as the preferred therapy.

PMID- 28457355
TI  - Chikungunya Virus.
AB  - For chikungunya virus (CHIKV), the long-term sequelae from infection are yet ill
      defined. The prolonged debilitating arthralgia associated with CHIKV infection
      has tremendous potential for impacting the global economy and should be
      considered when evaluating the human burden of disease and the allocation of
      resources. There is much still unknown about CHIKV and the illnesses that it
      causes. Developing a better understanding of the pathogenesis of CHIKV infection
      is a priority and forms the basis for developing effective strategies at
      infection prevention and disease control.

PMID- 28457356
TI  - Rickettsiae as Emerging Infectious Agents.
AB  - With advances in molecular genetics, more pathogenic rickettsial species have
      been identified. Pathogenic rickettsiae are transmitted by vectors, such as
      arthropods, into the patient's skin and then spread into the microvascular
      endothelial cells. Clinical manifestations are characterized by fever with
      headache and myalgias, followed by rash 3 to 5 days later. The undifferentiated
      nature of clinical symptoms, knowledge of the epidemiology, and the patient's
      history of travel and exposure to arthropod vectors are critical to the empiric
      administration of antimicrobial therapy. Doxycycline is currently the most
      effective antibiotic for treatment of all spotted fever group and typhus group
      rickettsioses.

PMID- 28457357
TI  - Preface.

PMID- 28457358
TI  - Preface.

PMID- 28457359
TI  - Transport of Human Organs in Italy: Location, Time, and Performances.
AB  - INTRODUCTION: The outcome of transplantation activities depends on a variety of
      unpredictable factors. Up-to-date criteria on organ allocation foresee an
      efficient transport chain along with compliant performance parameters. METHODS
      AND OBJECTIVES: The Centro Nazionale Trapianti and the Department of Civil,
      Chemical, Environmental, and Materials Engineering of the University of Bologna
      (respectively, CNT and DICAM) have been updating a national database of organ
      transplantation activities to investigate performance parameters and the main
      causes of disruption. RESULTS: Between June 2015 and July 2016, 617 of 1061
      organs have been shipped by air (making for 486 flight events), of which 407 were
      accompanied by medical equipment. Origin/destination and distance matrixes have
      been drawn for both road and air transport. Each airport node is ranked based on
      the n degrees  of organs ingoing/outgoing and each route link on its frequency.
      Performance parameters such as average speed, distance covered, and time have
      been computed and compared with each organ's cold ischemia time (CIT). Average
      distance frontiers are rather homogeneous, but much effort is necessary to reduce
      the number of events performed with approximately 90% or more of CIT spent.
      CONCLUSIONS: The monitoring of organ transplantation activities' performance is a
      standalone action within Europe to support strategic policies to optimize the
      system. Thus, a clearer awareness on performances and issues related to organ
      transport has been made possible: analyses show that the higher uncertainty
      associated with total time of displacement by air is due to the steps which take
      place by road (length and paths must be optimized) and lung transports generally
      perform weaker than heart transports due to longer average distances travelled
      and smaller average speeds, often resulting in a total displacement time greater
      than 90% of CIT.

PMID- 28457360
TI  - Analysis of the Organ Offers Received From European Union Countries Before and
      After the Introduction of a Dedicated Information Technology Portal: The
      COORENOR/FOEDUS Portal.
AB  - INTRODUCTION: To optimize the use of nontransplantable organs in their own
      territory, the European Commission, as part of a project led by Italy, has
      promoted the use of an information technology (IT) portal, the COORENOR portal,
      developed by the Czech Republic in 2012, which evolved to become FOEDUS in 2015.
      METHODS: To evaluate the impact of the portal on our reality, we analyzed the
      number and type of offers received and organs imported in the previous 48 months
      (period A) as well as the 48 months after the introduction of the portal (period
      B). We also examined the origin and the offer mode. RESULTS: The offers received
      were 404 and 753, respectively, in the two periods, with 315 (41.8%) organs
      received through the portal. The organs transplanted were 53 and 64,
      respectively, in the two periods; 20 (31.2%) were sent through the portal. The
      most commonly offered organs are lungs (36.7% and 29.3% of offers in periods A
      and B, respectively). The most transplanted organ is the liver (59.4% and 45% of
      transplants in periods A and B, respectively). The use of the portal has
      gradually increased, growing from 16.4% of the offer mode in 2012 to 84.7% in
      2016. CONCLUSIONS: The increase of offers related to the increase of donations
      and the attitude to the sharing of resources has determined an increase of 19.2%
      of total transplants, especially for certain types such as pediatric transplants.
      The portal, ensuring speed and simultaneity of offer, real time sharing of
      information and transparency of allocation, is also used for trade in the
      International Partnership Agreements. Therefore, transplants have been
      conditioned by the existing agreements with Greece, Malta, and the countries of
      the South Transplant Alliance.

PMID- 28457361
TI  - Robot-Assisted Harvesting of Kidneys for Transplantation and Global Complications
      for the Donor.
AB  - INTRODUCTION: Robot-assisted kidney harvesting from living donors is feasible and
      safe. We report the results of a mono-centric experience relative to 98
      consecutive robotic nephrectomies with emphasis on global donor complications.
      MATERIALS AND METHODS: This is a retrospective cohort study. Donors underwent
      robot-assisted kidney harvesting. The preferred kidney was the left one even in
      the presence of vascular anomalies. In the first cases we used a robotic hand
      assisted technique, then the totally robotic technique, and finally the modified
      totally robot-assisted technique. Postoperative complications were ranked
      according to the five-grade Clavien-Dindo classification. RESULTS: Between
      November 2009 and November 2016, 98 living donors underwent nephrectomy. We
      experienced 14 complications. The 3 intraoperative ones (3.06%) were 1
      pneumothorax and 2 acute bleedings, 1 of them requiring transfusion. The 11
      postoperative complications (11.22%) were as follows: 5 wound seromas, 1
      rhabdomyolisis (Clavien I), 1 paretic ileum, 1 anemia requiring transfusion, 1
      hypertensive crisis (Clavien II), and 2 chylus collections drained by
      interventional radiologists (Clavien III). Transfusion rate was 2.1%;
      conversions, reoperations, and mortality were nil. No statistically significant
      difference was observed between the patients with complications and without in
      terms of gender, age, anatomical anomalies, body mass index (BMI), and learning
      curve. We observed a longer global operation length of time in patients with
      complications. CONCLUSION: Robotic assistance results in shorter and simpler
      learning curves for the harvesting of kidneys from living donors. It enables an
      easier and more efficient management of possible intraoperative complications.
      The rate of postoperative complications is comparable with the rate of
      complications encountered in traditional laparoscopic series with high numbers of
      harvestings.

PMID- 28457362
TI  - Pre-Emptive Therapy for the Treatment of Cytomegalovirus After Kidney
      Transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) represents the leading cause of viral infection
      in kidney transplantation patients. The aim of the present study was to evaluate
      the efficacy and safety of pre-emptive anti-CMV therapy. MATERIALS AND METHODS:
      We performed a retrospective analysis based on data from 227 consecutive patients
      transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor,
      considering: incidence of rejection, CMV organ localization, and graft and
      patient survival. All patients underwent induction immunosuppressive therapy
      followed by maintenance therapy consisting of corticosteroids, antimetabolites,
      and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of
      plasma CMV-DNA in the post-transplantation period was: weekly (first month),
      quarterly (second through twelfth month), and then half-yearly. RESULTS: CMV
      viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482
      copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity
      after a median period of 2.5 months from kidney transplantation (range: 0.2
      months to 43 months). A total of 49 of 227 (21.5%) patients were treated with
      antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal
      = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a
      rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%)
      patients died (noninfectious CMV-related complications = 8, cardiovascular causes
      = 6, bleeding complications = 1). CONCLUSION: Our experience confirms the
      validity of the pre-emptive anti-CMV therapy in renal transplantation patients.

PMID- 28457363
TI  - Alexithymia in Kidney Transplantation Patients.
AB  - Alexithymia is a marked difficulty in recognizing, exploring, and expressing
      inner feelings. Studies have proven the presence of a significant proportion of
      patients with alexithymia in samples from the transplantation population. This
      study aims to analyze the presence of alexithymia in a sample of 32 kidney
      transplantation patients from a deceased donor and to compare this construct with
      the presence of psychological symptoms and the physical and mental state of
      health perceived by the patients. Alexithymia assessment was analyzed using the
      Toronto Alexithymia Scale. The psychological symptoms were studied through the
      Symptom Checklist-90-R. The quality of life was studied through The Complete Form
      Health Survey. The study showed a high percentage of the presence of alexithymia
      in the examined transplant recipients. The construct is more present where the
      perception of their quality of life is low and where there is a greater presence
      of psychosomatic symptoms.

PMID- 28457364
TI  - Bariatric Surgery to Target Obesity in the Renal Transplant Population:
      Preliminary Experience in a Single Center.
AB  - During the last century, obesity has become a global epidemic. The effect of
      obesity on renal transplantation may occur in perioperative complications and
      impairment of organ function. Obese patients have metabolic derangements that can
      be exacerbated after transplantation and obesity directly impacts most
      transplantation outcomes. These recipients are more likely to develop adverse
      graft events, such as delayed graft function and early graft loss. Furthermore,
      obesity is synergic to some immunosuppressive agents in triggering diabetes and
      hypertension. As behavioral weight loss programs show disappointing results in
      these patients, bariatric surgery has been considered as a means to achieve rapid
      and long-term weight loss. Up-to-date literature shows laparoscopic bariatric
      surgery is feasible and safe in transplantation candidates and increases the rate
      of transplantation eligibility in obese patients with end-stage organ disease.
      There is no evidence that restrictive procedures modify the absorption of
      immunosuppressive medications. From 2013 to 2016 we performed six bariatric
      procedures (sleeve gastrectomy) on obese patients with renal transplantation;
      mean preoperative body mass index (BMI) was 39.8 kg/m2. No postoperative
      complication was observed and no change in the immunosuppressive medications
      regimen was needed. Mean observed estimated weight loss was 27.6%, 44.1%, 74.2%,
      and 75.9% at 1, 3, 6, and 12 months follow-up, respectively. Our recommendation
      is to consider patients with BMI >30 kg/m2 as temporarily ineligible for
      transplantation and as candidates to bariatric surgery if BMI >35 kg/m2. We
      consider laparoscopic sleeve gastrectomy as a feasible, first-choice procedure in
      this specific population.

PMID- 28457365
TI  - Understanding Bone Damage After Kidney Transplantation: A Retrospective
      Monocentric Cross Sectional Analysis.
AB  - BACKGROUND: Kidney transplantation (KT) immunosuppression may induce bone tissue
      damage with bone mineral density (BMD) loss increasing bone fractures risk.
      Steroid therapy is considered the major player, but others factors are still
      under review. PATIENTS AND METHODS: We designed an observational retrospective
      cohort study to evaluate bone damage after KT. The prevalence of osteopenia,
      osteoporosis, bone fractures, and the associated risk factors were investigated.
      The following parameters were recorded before transplantation and at the last
      follow-up: demographic indexes, cumulative steroid dose (CSD), dialytic and
      transplantologic age, previous nephropathy, femoral and lumbar BMD, fractures,
      immunosuppressors, calcemia, phosphoremia, rejection episodes, estimated
      glomerular filtration rate, and parathyroid hormone and vitamin D levels. Stata
      software (Stata Corporation, College Station, Texas, United States) was used for
      the statistical analysis, to perform the Fisher's exact test, Kruskal-Wallis
      test, Student t test, as well as univariate and multivariate analyses. RESULTS:
      The analyzed cohort was composed of 297 patients (65.3% males and 34.7% females).
      Sixty percent of KT patients had normal BMD, 24% had osteopenia, and 15% had
      osteoporosis. Twelve percent were victims of bone fractures (8.4% minor, 2%
      femoral, and 1.7% vertebral). A significant correlation (P <.05) was observed for
      both osteopenia and osteoporosis with menopause, transplantologic age, CSD,
      previous glomerulonephritis, and mammalian target of rapamycin (mTOR) inhibitors
      treatment (imTOR). CONCLUSION: This study confirms the correlation between CSD
      (both before and after transplantation) and post-transplantation bone damage. It
      also shows that a large fraction of these patients had normal BMD related with a
      low steroid dose in our protocols. This correlation between imTOR assumption and
      osteoporosis deserves attention and warrants further in vitro analyses to be
      performed.

PMID- 28457366
TI  - Hepatitis C Virus Positive Patients on the Waiting List for Liver
      Transplantation: Turnover and Characteristics of the Population on the Eve of the
      Therapeutic Revolution With Direct-Acting Antivirals.
AB  - INTRODUCTION: Antivirals direct acting (DAA) for hepatitis C virus (HCV) have
      brought a revolution in the field of transplantation. It is likely to think that
      in the future patients on the waiting list for liver transplantation (LT) will no
      longer be registered for HCV-related cirrhosis but for liver disease from other
      causes. On the eve of this change, we show a snapshot of the Italian waiting list
      for LT. METHODS: From October 1, 2012 to September 30, 2013, we estimated the
      total number of patients on the liver waiting list as intention to treat (ITT),
      the number of incident cases, and the delistings, particularly in the HCV
      positive (HCV+) population. Gender, median age, etiology and prognosis of liver
      disease, presence of hepatocellular carcinoma (HCC), reason for delisting, mean
      waiting time for LT, and rate of death on waiting list were evaluated. RESULTS:
      In the time period, there were 517 new patients who were HCV+ (median age, 53
      years): 255 (49.3%) mono-infected with HCV, 236 (45.7%) co-infected with HCV and
      hepatitis B virus (HBV), 11 (2.1%) co-infected with HCV and human
      immunodeficiency virus (HIV), and 15 (2.9%) co-infected with HCV, HBV, and HIV.
      The median model for end-stage liver disease (MELD) score at listing was 17 and
      HCC was present in 206 (39.8%) cases. HCV+ patients delisted were 442 (61.9%),
      355 (80.3%) for LT. The mean waiting time to transplantation was 1.9 months; the
      percentage of death was 7.6%. CONCLUSIONS: This snapshot of the waiting list for
      LT in the year before the advent of DAA drugs will allow us to assess whether and
      how they will change the waiting list for LT when we start to look at the impact
      of new therapies on the waiting list.

PMID- 28457368
TI  - Eradication of Hepatitis C After Liver Transplantion: Consequences for the
      Organization of the Transplant Patient's Follow-up.
AB  - The recurrence of the hepatitis C virus (HCV) in the liver graft has been so far
      the main cause of morbidity and mortality in post-transplantation patients. The
      treatment has significantly committed the resources of transplant hepatologists
      despite the poor results obtained with the past standard treatment with the use
      of interferon plus ribavirin. The new direct-acting antivirals (DAAs) are safe
      and effective even in the transplant setting, and our purpose was to check
      whether the eradication of HCV can make predominant other clinical problems that
      require different skills from those classic to hepatology. Prevalence of
      different items, such as metabolic syndrome, chronic renal insufficiency, and
      post-transplantation neoplasms, analyzed in the pre-DAA and post-DAA periods
      within a homogeneous population of all-cause and HCV transplant patients referred
      to our local hepatology service resulted in an increase in the post-DAA period
      after the substantial eradication of HCV. The suggestion that the main active
      issue has become extrahepatic sets the stage for the diversification of resources
      to be committed in the follow-up of liver transplantation.

PMID- 28457367
TI  - Fast Chromotrope Aniline Blue Special Stain Is a Useful Tool to Assess Fibrosis
      on Liver Biopsy During Transplantation.
AB  - BACKGROUND: Assessment of potential liver allograft donors with frozen sections
      has clinical relevant consequences for the transplant recipient. Several clinical
      risk factors have been identified that increase the risk of transplantation
      failure and it is critical for the pathologist to become familiar with the
      histologic criteria for donor liver suitability. In this setting an accurate and
      reliable assessment of fibrosis is crucial. We sought to report the value of the
      rapid chromotrope aniline blue stain (CAB) in a transplantation clinical work
      flow for scoring liver fibrosis. MATERIALS AND METHODS: Twenty consecutive
      intraoperative donor liver biopsy specimens were evaluated by a pathologist at
      the Transplant Pathology Board Room, AOUI Verona, during 24-hour on-call service.
      The stage of fibrosis was evaluated according to Ishak score ranging from 0 to 6
      (absent to cirrhosis) using hematoxylin and eosin stain (H&E) plus rapid CAB
      special stain. After a 3-week washout period, only the slides stained with H&E
      were re-assessed for fibrosis stage by the same pathologist blinded to donor
      patient data. RESULTS: Combination H&E-CAB staging fibrosis score was higher in
      20%, lower in 10%, and the same in 70% of biopsy specimens as determined using
      only H&E stain alone. Rapid CAB stain takes 20 minutes longer than H&E stain
      alone. CONCLUSIONS: CAB staining may be performed on frozen tissue from liver
      biopsy during a transplantation process without a significant delay in diagnosis.
      Combination H&E-CAB staining improves sensibility of interpretation of fibrosis.

PMID- 28457369
TI  - Safety and Efficacy of Citrate Anticoagulation for Continuous Renal Replacement
      Therapy for Acute Kidney Injury After Liver Transplantation: A Single-Center
      Experience.
AB  - BACKGROUND: Acute kidney injury (AKI) after liver transplantation (LT) is a
      frequent and serious complication. The incidence of AKI requiring continuous
      renal replacement therapy (CRRT) ranges from 10% to 30%. Kidney Disease:
      Improving Global Outcomes guidelines indicate the use of citrate as a
      locoregional anticoagulant drug for CRRT regardless of the patient's hemorrhagic
      risk. Despite this indication, however, the use of citrate is still under debate
      in patients with liver failure and/or LT owing to the potential risk of plasmatic
      citrate accumulation due to reduced liver clearance. The aim of this study was to
      evaluate the safety and efficacy of citrate as a locoregional anticoagulation
      drug in CRRT for AKI after LT. METHODS: A retrospective analysis was performed in
      patients with AKI after liver transplantation who were treated with CRRT using
      citrate as local anticoagulant. Five patients were enrolled from January to
      December 2015. RESULTS: No patients showed complications related to citrate
      (metabolic acidosis, hyperlactatemia, hypercalcemia, or hypernatremia). All
      treatments with heparin were stopped owing to circuit clotting. Treatments with
      citrate was interrupted where it was no longer needed or when other examinations
      had to be made. None were stopped because of circuit coagulation. CONCLUSIONS: At
      our center, 5 patients have been successfully treated with the use of CRRT with
      citrate for AKI during the post-LT course. Our results, though on a small series
      of patients, provide evidence that CRRT with citrate can be a safe and promising
      treatment for AKI after LT.

PMID- 28457370
TI  - Carbapenem-Resistant Klebsiella Pneumoniae Infections Early After Liver
      Transplantation: A Single-Center Experience.
AB  - The aims of this study were to define in a cohort of 310 liver transplant
      recipients, the incidence of post-liver transplantation (LT) non-carbapenem
      resistant Klebsiella pneumoniae (CRKP) and CRKP infections, pre- and post-LT CRKP
      colonization, CRKP-associated mortality, and risk factors for non-CRKP and CRKP
      infections. Every patient was screened for CRKP immediately before and after LT.
      The 6-month survival rate was 95%. Fifty-two patients became infected (16.5%): 8
      by CRKP (2.5%) and 44 (14%) by a non-CRKP micro-organism. Median onset of CRKP
      infections occurred at postoperative (POD) 12 (range, 4-70). CRKP colonization
      occurred in 20 patients (6%): 10 before LT (3 infected and died) and 10 after (5
      infected, 3 died). CRKP- versus non-CRKP-infected patients had higher rates of
      intensive care unit (ICU) and hospital mortality (50% vs 20% and 62.5% vs 36%; P
      <= .001), septic shock (87% vs 34%; P = .0057; confidence interval [CI], 9.8
      71.5), prolonged mechanical ventilation (100% vs 64%; P = .043, CI, 3.5-51.9),
      and renal replacement therapy (87% vs 41%; P = .0177; CI, 2.8-65). The small
      number of CRKP-infected patients did not allow the definition of specific risk
      factors for CRKP infection. At univariate analysis, pre- and post-LT colonization
      (odds ratio [OR], 10.76; CI, 2.6-44; OR, 14.99; CI, 3.83-58.66, respectively),
      relaparotomy (OR, 9.09; CI, 4.01-20.6), retransplantation (OR, 7.45; CI, 3.45
      16), bile leakage (OR, 61.28; CI, 9.23-80), and early allograft dysfunction (EAD;
      OR, 5.7; CI, 3-10.7) were significantly associated with infections, making CRKP
      colonization (any time) and post-LT surgical and medical complications critical
      factors for post-LT CRKP infections.

PMID- 28457372
TI  - Lung Transplantation From Donors After Previous Cardiac Surgery: Ideal Graft in
      Marginal Donor?
AB  - Lung transplantation is a limited by donor pool shortage. Despite the efforts to
      extend the graft acceptability with recurrent donor criteria reformulations,
      previous cardiothoracic surgery is still considered a contraindication. A donor
      who underwent cardiac surgery could potentially provide an ideal lung but high
      intraoperative risks and intrinsic technical challenges are expected during the
      graft harvesting. The purpose of this study is to present our dedicated protocol
      and four clinical cases of successful lung procurements from donors who had a
      previous major cardiac surgery. One donor had ascending aortic root (AAR)
      substitution, another had mitral valve substitution, and two had coronary artery
      bypass surgery. The others' eligibility criteria for organ allocation, such as
      ABO compatibility, PaO2/FiO2 ratio, absence of aspiration, or sepsis were
      respected. In one of the cases with previous coronary bypass grafting, the donor
      had a veno-arterial extracorporeal membrane oxygenation support. Consequently,
      the grafts required an ex vivo lung perfusion evaluation. We report the technical
      details of procurement and postoperative courses of recipients. All procurements
      were uneventful, without lung damage or waste of abdominal organs related to
      catastrophic intraoperative events. All recipients had a successful clinical
      outcome. We believe that successful transplantation is achievable even in a
      complicated setting, such as cases involving donors with previous cardiac surgery
      frequently are. Facing lung donor shortage, we strongly support any effort to
      avoid the loss of possible acceptable lungs. In particular, previous major
      cardiac surgery does not strictly imply a poor quality of lungs as well as
      unsustainable graft procurement.

PMID- 28457371
TI  - Lobar Lung Transplantation From Deceased Donor: Monocentric Experience.
AB  - INTRODUCTION: Lung transplantation is considered a therapeutic option in selected
      patients affected by end-stage pulmonary disease. The mortality on the waiting
      list is mainly attributed to the shortage of the donor pool available for
      transplantation. There are various strategies to overcome this shortage; one of
      them is lobar transplantation. METHODS: The aim of the current study was to
      analyze the outcome of lobar lung transplantation from deceased donors in our
      Lung Transplant Center. Overall survival, perioperative mortality and morbidity,
      problem on bronchial anastomosis, and chronic rejection were prospectively
      recorded in a 5-year time-frame. RESULTS: From November 2010 to October 2015, we
      performed 100 lung transplantations; 6 of which (6%) were lobar transplantations
      from deceased donors. Three recipients were on an emergency list due to
      preoperative extracorporeal support. The causes of lobectomy leading to lobar
      transplantation were: size mismatch (3), iatrogenic vascular damage (2), and
      chronic atelectasis (1). One patient died 5 months after surgery for sepsis; and
      5 patients were alive at the study end (median follow-up: 17.5 months).
      Prevalence of grade 3 primary graft dysfunction at 72 hours was 50%. One patient
      developed bronchial stenosis. No cases of chronic rejection were recorded.
      CONCLUSIONS: Lobar transplantation can be considered a valid tool to overcome the
      donor pool shortage in selected cases; such a technique has proved particularly
      useful in critically ill patients who were scheduled in an emergency transplant
      program.

PMID- 28457373
TI  - Optimizing the Use of Available Lungs.
AB  - BACKGROUND: Organ transplantation, the treatment of choice in organ failure, is
      penalized by the lack of organs. Because the increase in the number of donors is
      not proportional throughout the different age groups, there is no increase in
      lung transplantations. The aim of this work was to analyze the use of available
      lungs and evaluate strategies that may help increase transplantations. METHODS:
      We analyzed the activity of lung transplantation in 2015, divided into various
      allocation programs. We also examined the surplus organs, in particular, their
      origin, their destination, their offer's outcome, the characteristics of the
      donor and the proposed organ, and the reasons for rejection. RESULTS: In 2015,
      112 lung transplantations were performed: 66 (68.9%) with regional organs, 46
      (41.1%) with extraregional organs; 21 (45.6%) of these were allocated as
      emergencies/return, and 25 (54.4%) as surplus (19 in the North macroarea, 6 in
      the South macroarea). The number of surplus lungs was 148: 67 from the North
      macroarea, 71 from the South macroarea, and 10 from abroad. No organ procured in
      the North macroarea was transplanted in the South macroarea, whereas 6 lungs
      coming from the South macroarea were transplanted in the North. CONCLUSIONS: The
      acceptance criteria are not the same in different transplant centers and they
      include not only clinical parameters, but also ischemia time and composition of
      the waiting list at the time of the offer, quality and accessibility of the
      intensive care units where the donor is located, and organizational reasons.
      Offering organs which can not be transplanted within the region to other centers,
      without clinical foreclosures is a system that increases transplant activities by
      maximizing the available resources.

PMID- 28457374
TI  - Efficacy of Extracorporeal Photopheresis in Patients With Bronchiolitis
      Obliterans Syndrome After Lung Transplantation.
AB  - BACKGROUND: Lung transplantation (LT) is only therapeutic option for patients
      affected by chronic respiratory failure. Chronic rejection, also known as
      bronchiolitis obliterans syndrome (BOS), is still the main cause of death and the
      most important factor that influences post-transplantation quality of life.
      Currently available therapies have not been proven to result in significant
      benefit in the prevention or treatment of BOS. Extracorporeal photopheresis (ECP)
      seems to reduce the rate of lung function decline in transplant recipients with
      progressive BOS. METHODS: From 1991 until now, 239 LTs were performed at our
      center. Fifty-four patients (22.5%) developed BOS; 15 of these (27.7%) were
      treated with ECP. At the beginning of the treatment, all patients showed a mean
      decline of forced expiratory volume in 1 second (FEV1) from baseline values of
      45.8% +/- 17.2%; 2 patients were in long-term oxygen therapy. RESULTS: Mean
      follow-up from November 2013 to June 2016 was 11.6 +/- 7 months. Twelve patients
      (80%) showed lung function stabilization with an FEV1 range after treatment
      between -6% to +8% from the pre-treatment values. We did not report any adverse
      effects or increase of infections incidence. DISCUSSION: ECP seems to be an
      effective and well-tolerated therapeutic option for LT patients with BOS in terms
      of stabilization of lung function and increased survival.

PMID- 28457375
TI  - Evaluation of Renal Function in Patients Undergoing Lung Transplantation.
AB  - BACKGROUND: Acute kidney injury and chronic kidney failure are serious
      complications after lung transplantation. Glomerular filtration rate (GFR) is the
      primary indicator of renal function. Several equations have been proposed to
      evaluate the estimated GFR (eGFR). We compared three different equations to
      determine which has the better correlation with the development of acute and
      chronic renal failure in lung recipients. METHODS: Twenty-two patients with a
      mean age of 54.4 +/- 8.5 years underwent lung transplantation from 2010 to 2015.
      Thirteen (59%) had pulmonary fibrosis, 7 (32%) emphysema, 1 (4.5%)
      bronchiectasis, and 1 (4.5%) lymphangioleiomyomatosis. In all patients, eGFR was
      measured preoperatively using Cockcroft-Gault (CG), Modification of Diet in Renal
      Disease (MDRD), and Levey's Chronic Kidney Disease Epidemiology Collaboration
      (CKD-EPI) equations. In 20 patients (90%) eGFR was calculated at 1, 3, and 6
      months. RESULTS: According to CKD-EPI and MDRD, eight patients (36.3%) had
      preoperative reduction in eGFR, whereas 6 patients (27.2%) had preoperative
      reduction according to the CG (P = .04). The mean values were higher for the CG
      (103.2 vs. 102 vs. 94.4). Five patients (22.7%) developed perioperative acute
      renal failure requesting a dialysis treatment; four of these showed a
      preoperative eGFR to the highest CG (P = .05). At 1 and 6 months after lung
      transplantation, the CG, MDRD and CKD-EPI eGFR values were, respectively, 86.6,
      84.1 and 76.6 mL/min/1.73m2 and 75.8, 72.7, and 72.3 mL/min/1.73m2. CKD-EPI eGFR
      values are more predictable than the other equations of AKI. CONCLUSIONS:
      Preoperative assessment of eGFR using the MDRD and CKD-EPI seems to correlate
      better than the CG to the prediction of acute renal failure, whereas for the
      chronic form the three equations seem equivalent.

PMID- 28457376
TI  - Selection of Candidates for Lung Transplantation: The First Italian Consensus
      Statement.
AB  - Lung transplantation is a well-established treatment for selected patients with
      advanced chronic respiratory insufficiency. Recognizing those patients with end
      stage lung disease who might benefit from lung transplantation is a crucial task.
      Considering the presence of inadequate evidence-based practice, international and
      national scientific societies provided consensus opinions regarding the
      appropriate timing of listing. The Study Group for Thoracic Organs
      Transplantation (branch of the Italian Society for Organs Transplantation)
      promoted and realized a Delphi conference among the Italian lung transplantation
      centers to provide guidance to clinical practice based on international
      recommendations. The experts from the nine Italian centers completed two rounds
      of standardized questionnaires (answer rate, 100%): 42 statements received a
      consensus >=80%. The selected statements presented in this article are intended
      to assist Italian clinicians in selecting patients for lung transplantation.

PMID- 28457377
TI  - Ethical Issues in Uterine Transplantation: Psychological Implications and
      Informed Consent.
AB  - Since 2000, 13 uterine transplantations (UTxs) have been performed in women with
      absolute uterine infertility factor (AUIF), from both living and deceased donors,
      in different transplantation centers worldwide. At present the birth of 4
      children following UTx is documented by the literature, and a woman was having a
      second pregnancy in October 2015. Following these successes it is likely that the
      procedure will become part of normal healthcare practice, even though at the
      moment it is still experimental and, as such, requires careful attention. Because
      the emotional aspects that are tied to UTx may foster the "therapeutic
      misconception" of participants, which consists in an overestimation of the
      benefits and an underestimation of the risks, careful attention should be paid
      also to informed consent (IC), which must include the following: describing
      techniques, pointing out risks and possibility of failure, and informing about
      the treatments required after the intervention. Because the final aim of UTx is
      the birth of a healthy child, the IC document must include details not only of
      the transplantation itself, but also of the very particular pregnancy deriving
      from it, and the need to remove the uterus following delivery(ies) to avoid these
      risks. Here we suggest that the IC process includes counselling techniques,
      possibly involving the psychologist that is part of the transplantation team, to
      target the information and decision-making process to the specific situation of
      each couple.

PMID- 28457378
TI  - Electrospun Polyhydroxyethyl-Aspartamide-Polylactic Acid Scaffold for Biliary
      Duct Repair: A Preliminary In Vivo Evaluation.
AB  - Tissue engineering has emerged as a new approach with the potential to overcome
      the limitations of traditional therapies. The objective of this study was to test
      whether our polymeric scaffold is able to resist the corrosive action of bile and
      to support a cell's infiltration and neoangiogenesis with the aim of using it as
      a biodegradable tissue substitute for serious bile duct injuries. In particular,
      a resorbable electrospun polyhydroxyethyl-aspartamide-polylactic acid (90 mol%
      PHEA, 10 mol% PLA)/polycaprolactone (50:50 w/w) plate scaffold was implanted into
      rabbit gallbladder to assess the in vivo effects of the lytic action of the bile
      on the scaffold structure and then as a tubular scaffold to create a biliary
      digestive anastomosis as well. For the above evaluation, 5 animals were used and
      killed after 15 days and 5 animals after 3 months. At 15-day and 3-month follow
      ups, the fibrillar structure was not digested by lytic action bile. The fibers of
      the scaffold were organized despite being in contact with bile action. A new
      epithelial tissue appeared on the scaffold surface suggesting the suitability of
      this scaffold for future studies of the repair of biliary tract injuries with the
      use of resorbable copolymer on biliary injuries.

PMID- 28457379
TI  - Electrospun PHEA-PLA/PCL Scaffold for Vascular Regeneration: A Preliminary in
      Vivo Evaluation.
AB  - BACKGROUND: There is increasing interest in the development of vessel
      substitutes, and many studies are currently focusing on the development of
      biodegradable scaffolds capable of fostering vascular regeneration. We tested a
      new biocompatible and biodegradable material with mechanical properties similar
      to those of blood vessels. METHODS: The material used comprises a mixture of
      alpha,beta-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) and polylactic acid
      (PLA), combined with polycaprolactone (PCL) by means of electrospinning
      technique. Low-molecular-weight heparin was also linked to the copolymer. A
      tubular PHEA-PLA/PCL sample was used to create an arteriovenous fistula in a pig
      model with the use of the external iliac vessels. The flow was assessed by means
      of Doppler ultrasound examination weekly, and 1 month after the implantation we
      removed the scaffold for histopathologic evaluation. RESULTS: The implants showed
      a perfect leak-proof seal and adequate elastic tension to blood pressure. About
      ~3 weeks after the implantation, Doppler examination revealed thrombosis of the
      graft, so we proceeded to its removal. Histologic examination showed chronic
      inflammation, with the presence of foreign body cells and marked
      neovascularization. The material had been largely absorbed, leaving some isolated
      spot residues. CONCLUSIONS: The biocompatibility of PHEA-PLA/PCL and its physical
      properties make it suitable for the replacement of vessels. In the future, the
      possibility of functionalizing the material with a variety of molecules, to
      modulate the inflammatory and coagulative responses, will allow obtaining devices
      suitable for the replacement of native vessels.

PMID- 28457380
TI  - Overexpression of Hypoxia-Inducible Factor-1alpha in Primary Graft Dysfunction
      Developing in an Orthotopic Lung Transplantation Rat Model.
AB  - BACKGROUND: Primary graft dysfunction (PGD) is the major cause of early morbidity
      and mortality after transplantation. A high rate of PGD is a frequent
      complication in orthotopic lung transplantation (OLT) models, which are currently
      used to investigate acute and chronic rejection pathways. Hypoxia-inducible
      factor (HIF)-1alpha is a heterodimeric alphabeta transcription factor that
      mediates tissue response to hypoxia. In other solid organ transplantations, a
      significant correlation between HIF-1alpha expression and PGD was detected. To
      our knowledge no data are available on HIF-1alpha expression in PGD developing in
      lung transplantation. The aims of this study were to investigate HIF-1alpha
      expression (using immunohistochemistry) and correlate it to the main histological
      parameters related to ischemia-reperfusion (IR) injury, including terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) -positive apoptotic
      cells). METHODS: OLT was performed in 32 inbred rat strains and 11 of them died
      in the early postoperative period (from day 0-3) for IR injury. The histological
      and molecular evaluations were done in all lung tissues. Unimplanted donor rat
      lungs were used as controls. HIF-1alpha expression was correlated with all
      morphological parameters. RESULTS: Lung samples of animals with IR injury showed
      high scores of HIF-1alpha expression, edema, blood extravasation, granulocyte
      margination, apoptotic index, and necrosis in 91% of cases. Tissue overexpression
      of HIF-1alpha was detected in all lung samples with high scores of histological
      parameters and with high apoptotic indexes. CONCLUSION: Our data demonstrate that
      HIF-1alpha was overexpressed in more severe rat lung IR injury. The use of HIF
      1alpha inhibitors could provide a translatable route into manipulating this
      complex system in vivo.

PMID- 28457382
TI  - Case Report: Aortic Valve Replacement After JARVIK 2000 Left Ventricular Assist
      Device Implantation in Long-Time Survivor With Severe Aortic Valve Regurgitation.
AB  - BACKGROUND: There are limited clinical records in the literature regarding aortic
      valve replacement in left ventricular assist device (L-VAD) patients. Previously
      we had two cases of severe aortic valve regurgitation in patients with L-VAD
      support treated with Corvalve prosthesis insertion and Amplatzer closure
      procedure. Both patients died a few days after the procedure from complications
      not related to the procedure itself. PATIENT HISTORY: The patient was a male with
      previous coronary artery bypass graft surgery in 2001 that was complicated with
      postischemic dilated cardiomyopathy with severe heart failure (ejection fraction
      [EF], 20%). Cardiac resynchronization therapy was biventricular-pacemaker and
      cardiac defibrillator implantation in 2009 for recurrent ventricular arrhythmia.
      L-VAD implantation (Jarvik 2000) with graft apposition in descending thoracic
      aorta through left thoracotomy access and retro-auricolar cable was performed in
      October 2013. In 2015 the patient underwent surgical aortic valve replacement
      with bioprothesis due to progressive worsening of the aortic valve regurgitation.
      The Jarvik 2000 outflow was occluded with vascular ball occluder inserted via
      right axillary artery under fluoroscopy before CEC installation. The recovery was
      without major complications. DISCUSSION: Long-time survivors with Jarvik 2000 are
      increasing in number and such late complication is expected to become a main
      future issue. Our previous experience with the interventional approach was
      delusive. Due to the fatal consequences in similar patients with nonsurgical
      approaches, we opted for surgical aortic valve replacement. At the moment, the
      international literature does not describe safe approaches regarding aortic valve
      replacement in patients with Jarvik 2000 L-VAD. This case shows that surgical
      valve replacement could be managed with success according to the described
      specific technique.

PMID- 28457381
TI  - Salvage of an Octogenarian Liver Graft Using Normothermic Perfusion: A Case
      Report.
AB  - Liver transplantation with very old donors is safe, but is associated with an
      increased incidence of ischemic-type biliary lesions and delayed graft function.
      Normothermic machine perfusion (NMP) is a novel technique for preservation of
      liver grafts and has the potential to reduce ischemia-reperfusion injury. A case
      is reported here of a liver transplantation (LT) with a graft from an 83-year-old
      brain-dead donor. Procurement was with dual perfusion and en bloc, modified fast
      technique. Donor kidneys were not transplanted due to severe atherosclerosis and
      poor perfusion. The liver was shipped to the transplantation center and underwent
      NMP with a blood-based perfusate. During machine perfusion lactates decreased,
      vascular flow was stable, and bile production restored, and the graft was
      considered suitable for transplantation. The postoperative course was uneventful
      and 4 months after surgery the patient is in good clinical condition with normal
      liver function. To date, few LTs have been performed with NMP in humans, but its
      preliminary results are promising. NMP allows functional evaluation of the graft
      and possibly reduction of post-transplantation complications when extended
      criteria donor grafts are used.

PMID- 28457383
TI  - Kidney Transplantation in Alstrom Syndrome: Case Report.
AB  - The Alstrom syndrome is a rare genetic disorder, inherited in an autosomal
      recessive manner. It has recently been classified as a ciliopathic disorder.
      Alstrom syndrome is a multiorgan pathology characterized by cone-rod dystrophy,
      hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia,
      type 2 diabetes mellitus, dyslipidemia, short stature in adulthood,
      hypothyroidism, hypogonadism, dilated or restrictive cardiomyopathy, and
      progressive pulmonary, hepatic, and renal dysfunction. End-stage renal disease
      can occur as early as the late teens and is the leading cause of death. More than
      900 people with Alstrom syndrome have been reported worldwide. We present a case
      of a 42-year-old man affected by this syndrome with end-stage renal disease, type
      2 diabetes mellitus, and loss of visual function and hearing who received a
      kidney transplant from a cadaveric donor. Basiliximab and steroid were used as
      induction therapy. Tacrolimus, mycophenolate mofetil, and steroid were used as
      maintenance therapy. No complications were reported during the recovery. In
      selected patients affected by Alstrom syndrome, renal transplantation can be a
      successful treatment for chronic kidney disease.

PMID- 28457384
TI  - Liver Retransplantation for Hepatic Abscess Due to Hepatic Artery Thrombosis: A
      Case Report.
AB  - INTRODUCTION: Hepatic artery thrombosis (HAT) is a well-recognized complication
      of liver transplantation (LT). HAT is an important risk factor for infectious, in
      particular hepatic abscess, which can cause graft loss and increasing morbidity
      and mortality. CASE REPORT: We present a case report of complicated LT in a 52
      year-old Caucasian man with primary sclerosing cholangitis. In 2007 the patient
      was included on the waiting list in Padua for LT. In 2012 the patient underwent
      percutaneous transhepatic biliary drainage for bile duct stricture, complicated
      with acute pancreatitis. A diagnostic laparoscopy was performed with
      choledochotomy and Kehr's T tube drainage. On February 14, 2012, the patient
      underwent LT with arterial reconstruction and choledochojejunostomy. The
      postoperative course was complicated with HAT, multiple liver abscesses, and
      sepsis associated with bacteremia due to Enterococcus faecium despite massive
      intravenous antibiotic therapy and percutaneous drainages. On November 28, 2012,
      the patient underwent retransplantation. Four years after transplantation the
      patient is still in good general condition. CONCLUSION: Hepatic abscess formation
      secondary to HAT following LT is a major complication associated with important
      morbidity and mortality. In selected cases retransplantation should be considered
      as our case demonstrates.

PMID- 28457385
TI  - Blood Lactate Concentrations Before and After Withdrawal of Life-Sustaining
      Treatments in Controlled Donation After Circulatory Death: A Case Report From
      Italy.
AB  - A 20-minute hands-off period with isoelectric electrocardiography (ECG)
      monitoring is currently required for the declaration of cardiac death in Italy,
      thus prolonging the warm ischemia time (WIT) during donation after circulatory
      death (DCD). Normothermic regional perfusion (NRP) can be a valid tool to
      optimize organ perfusion as a bridge to donation. A 62-year-old woman with
      catastrophic brain injury due to massive intracranial hemorrage, not fulfilling
      brain death criteria, underwent controlled DCD after withdrawal of life
      sustaining therapies (WLST). NRP was established after a functional WIT of 43
      minutes. Despite concerns regarding a prolonged WIT imposed by the national
      legislation on declaration of cardiac death, NRP was successful in restoring an
      adequate perfusion to liver and kidneys, as evidenced by a sustained reduction in
      blood lactate concentration. Liver and kidneys were successfully transplanted
      after ex vivo machine perfusion.

PMID- 28457387
TI  - Preface.

PMID- 28457386
TI  - First World Report of Internal Power Cable Repair in Left Ventricular Assist
      Device Jarvik 2000: Case Report.
AB  - BACKGROUND: There are limited clinical reports concerning internal power cable
      fixing in left ventricular assist device (L-VAD) patients. Actually there are no
      reports in the literature about Jarvik 2000 internal cable repair. We show the
      first description of a technique for surgical reparation of such a fatal
      complication. PATIENT HISTORY: The patient was a 62-year-old woman who had L-VAD
      implantation (Jarvik 2000) with outflow graft apposition in descending thoracic
      aorta through left thoracotomy access, in 2009. She arrived urgently on January
      25, 2014 for Jarvik 2000 dysfunction correlated with head movements. The neck X
      rays revealed the rupture of one of the nine power cables located inside the neck
      and the damaging of two more cables nearby to be ruptured. On the same day she
      got pump failure due to the final interruption of the remaining two cables, we
      were obliged to install femoro-femoral extracorporeal membrane oxygenation (ECMO)
      assistance, to repair the power cables, approaching them through a pacemaker
      extension cable. The L-VAD outflow was occluded with vascular ball occluder
      inserted via right axillary artery under fluoroscopy before ECMO installation. At
      the end the ECMO assistance was interrupted and the Jarvik 2000 was turned back
      on. The patient was dismissed from the hospital 12 days after the procedure.
      DISCUSSION: At the moment the international literature is poor regarding this
      issue. This case provides evidence that in emergency conditions ECMO assistance
      is mandatory and a hybrid surgical and radiological approach could help to repair
      the damage in safe conditions.

PMID- 28457388
TI  - Brain Death: Knowledge of Future Brazilian Physicians.
AB  - BACKGROUND: Thousands of people die on the waiting list for transplants. The
      shortage of organs and tissues for transplantation is considered a serious global
      problem. Brain death (BD) is the main source of organs for transplantations.
      OBJECTIVE: Given that BD is assessed by medical staff and that this diagnosis is
      ethically relevant, the goal of this work was to analyze the knowledge of 5th-
      and 6th-year medical students of Southern Brazil regarding the process of
      determining BD. METHOD: This observational, cross-sectional study was conducted
      between September 2013 and March 2014. RESULTS: A total of 635 students
      participated in the study, with 337 (53.1%) from public and 298 (46.9%) from
      private schools. Approximately 333 (52.4%) attended the 6th year of the medical
      program. The mean age of the students was 25.4 +/- 3.56 years, with a prevalence
      of females of 54.6% (347) and a prevalence of Catholic religion of 61.7% (392);
      84.2% of the students reported not feeling confident performing the BD protocol.
      A low percentage (15.7%) correctly answered 75% or more of the questions about
      BD, a criterion used to determine sufficient knowledge of BD. Approximately 45%
      (282) of respondents were not able to identify the patients who were candidates
      for the BD protocol. Analyzing the medical students' knowledge at the end of the
      program can provide information about the quality of undergraduate education on
      the topic of determining BD. CONCLUSION: It was concluded that 5th- and 6th-year
      medical students of Parana State have little knowledge about the BD protocol.

PMID- 28457389
TI  - Beliefs of Nursing Professionals in the Organ Donation Process for
      Transplantation.
AB  - BACKGROUND: This study sought to discover the beliefs of nursing professionals in
      the organ donation process and to establish a relationship between the training
      and the beliefs of these professionals. METHODS: This was a quantitative and
      exploratory study composed of 611 nursing professionals. The sample
      characteristics and the response frequencies were presented through the use of
      descriptive statistics. The Kruskal-Wallis test was used to evaluate the
      different results between the professional categories. RESULTS: When evaluating
      the association between professional nursing, technical and nursing auxiliaries,
      and beliefs in the donation process, significant differences were found regarding
      the belief that the transplant improves the quality of life of the recipient,
      that there is no death while there is a heartbeat, that people are hijacked for
      organ withdrawal, and that it is possible to buy an organ for transplantation.
      CONCLUSIONS: For the beliefs presented by nursing professionals, it is evident
      that there is a need for educational programs to deconstruct negative beliefs and
      promote change in the professionals' posture.

PMID- 28457390
TI  - Association Safety of Liver Preservation Solutions at the State University of
      Campinas From 2010 to 2014.
AB  - The probable reason for mixing solutions during the harvesting procedure is due
      to the presence of multiple transplant teams that have their own solution usage
      tradition. Despite numerous studies comparing the efficacy of different
      preservation solutions, there is no study addressing the associating solution and
      if there is any impact on liver graft and patient survival. The aim was to
      evaluate the effect of the association of preservation solutions during the
      harvesting procedure on liver transplantation outcomes, especially in relation to
      the degree of preservation injury in the postreperfusion period and patient
      survival. We analyzed 206 transplants that were distributed as follows: when
      there was association (89/206 = 43.2%) and when there was no association (117/206
      = 56.8%). There was a statistically significant difference in relation to the
      degree of preservation injury correlated to cold ischemia time (P = .009, odds
      ratio 1.992; 95% confidence interval 1.185-3.347). Severe harvesting (grades III
      and IV) was 71.8% when the solution was not associated (P = .008). There was no
      difference regarding patient survival either. We found that the association of
      liver preservation solutions has no impact on patient survival, so it can be done
      safely. The best survival rate was associated with minimal harvesting.

PMID- 28457391
TI  - Cross-Talk Between Sirtuin 1 and High-Mobility Box 1 in Steatotic Liver Graft
      Preservation.
AB  - BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide +-dependent
      histone deacetylase that regulates various pathways involved in ischemia
      reperfusion injury (IRI). Moreover, high-mobility group box 1 protein (HMGB1) has
      also been involved in inflammatory processes during IRI. However, the roles of
      both SIRT1 and HMGB1 in liver preservation is poorly understood. In this
      communication, we evaluated the potential relationship between SIRT1 and HMGB1 in
      steatotic and non-steatotic liver grafts preserved in Institute Georges Lopez
      solution (IGL-1) preservation solution enriched or not enriched with
      trimetazidine (TMZ). METHODS: Steatotic and non-steatotic livers were preserved
      in IGL-1 preservation solution (24 hours, 4 degrees C), enriched or not enriched
      with TMZ (10 MUmol/L), and then submitted to ex vivo reperfusion (2 hours; 37
      degrees C). Liver injury (AST/ALT) and function (bile output, vascular
      resistance) were evaluated. SIRT1, HMGB1, autophagy parameters (beclin-1, LC3B),
      PPAR-gamma, and heat-shock protein (HO-1, HSP70) expression were determined by
      means of Western blot. Also, we assessed oxidative stress, mitochondrial damage
      (glutamate dehydrogenase), and TNF-alpha levels. RESULTS: Elevated SIRT1 and
      enhanced autophagy were found after reperfusion in steatotic livers preserved in
      IGL-1+TMZ when compared with IGL-1. However, these changes were not seen in the
      case of non-steatotic livers. Also, HO-1 increases in the IGL-1 + TMZ group were
      evident only in the case of steatotic livers, whereas HSP70 and PPAR-gamma
      protein expression were enhanced only in non-steatotic livers. All reported
      changes were consistent with decreased liver injury diminution, ameliorated
      hepatic function, and decreased TNF-alpha and HMGB levels. In addition, the
      oxidative stress and mitochondrial damage were efficiently prevented by the IGL-1
      + TMZ use. CONCLUSIONS: SIRT1 is associated with HMGB1 decreases and increased
      autophagy in steatotic livers, contributing to increased tolerance to cold IRI.

PMID- 28457392
TI  - Long-Term Outcomes of Kidney Transplantation From Expanded-Criteria Deceased
      Donors: A Single-Center Experience.
AB  - BACKGROUND: Organ shortage has prompted the use of expanded-criteria donors
      (ECDs). Our objective was to compare long-term outcomes of kidney transplants
      from ECDs with those from concurrent standard-criteria donors (SCDs). In
      addition, we evaluated variables associated with graft survival in both groups.
      METHODS: We retrospectively reviewed all 617 deceased-donor kidney
      transplantations performed from 2005 to 2009 in our department. The population
      was divided according to donor status into ECD or SCD. Patients were followed
      until 5 years after transplantation, death, graft failure, or loss to follow-up.
      RESULTS: We transplanted 150 deceased-donor kidneys from ECDs and 467 from SCDs.
      ECD were older, more frequently women, had a lower pre-retrieval glomerular
      filtration rate, and more frequently died due to cerebrovascular accident. ECD
      recipients were older, presented a lower proportion of black race, more
      frequently were on hemodialysis, and presented a higher rate of first kidney
      transplants. Mean glomerular filtration rate was consistently lower in the ECD
      group. Patient and graft survivals were lower in the ECD group, but statistical
      significance was present only in graft survival censored for death with a
      functioning graft at 3 years and graft survival noncensored for death with a
      functioning graft at 5 years. Younger recipient ages, longer time on dialysis,
      acute rejection episodes, and glomerular filtration rate at 1 year after
      transplantation were independent risk factors for lower graft survival.
      CONCLUSIONS: Transplantation with the use of ECD kidneys provide quite
      satisfactory patient and graft survival rates despite their poorer long-term
      outcomes.

PMID- 28457393
TI  - Ureteral Stenosis After Renal Transplantation-A Single-Center 10-Year Experience.
AB  - BACKGROUND: Kidney transplantation (KT) is the definitive treatment for ESRD.
      Ureteral stenosis (US) is one of the most common urologic complications and has
      been reported in 2.6%-15% of KTs. METHODS: We reviewed data for 973 consecutive
      KT procedures performed at our center from January 2004 to September 2014, with
      evaluation of US management and recurrence rate. RESULTS: The 973 KTs were
      performed with the use of the direct ureterovesical (UV) implantation Paquin
      technique, and the mean follow-up time was 44.3 +/- 30.2 [range, 3-111] months.
      During this period, 33 cases of US (3.39%) were reported. The interval from KT to
      US diagnosis was 10.6 +/- 23.0 (range, 0.5-98.0) months. The majority of the US
      cases were located in the distal ureter and UV junction (83.9%), with only 2
      cases of middle ureter stenosis and 2 cases of ureteropelvic junction. Mean US
      length was 2.5 +/- 1.9 (range, 1.0-10.0) cm. Surgical management and global and
      treatment-specific recurrence rates were reviewed. Primary surgical treatment
      recurrence rate was higher for the endoscopic approach, with a mean global time
      from treatment to US recurrence of 6.9 +/- 16.3 (range, 0-65) months and a median
      of 2.0 months. Open surgical approach was the main recurrence treatment option
      (74%). There were 2 cases of graft loss. Success rate evaluation of overall and
      treatment-specific primary surgical management did not reveal significant
      differences (P > .05) according to stenosis length (<1.5, 1.5-3.0, or >3.0 cm),
      time between transplant and stenosis (<=3, 3-12, or >12 mo), or stenosis location
      (distal, middle, or upper ureter). However, there was clearly a trend to higher
      success rate in smaller stenosis (<1.5 cm) and early management (<=3 mo),
      particularly with the use of balloon dilation. CONCLUSIONS: US management should
      be decided on a case-by-case basis according to clinical characteristics,
      treatment-specific recurrence rate, and previous surgical options.

PMID- 28457394
TI  - Early Rehospitalization Post-Kidney Transplant Due to Infectious Complications:
      Can We Predict the Patients at Risk?
AB  - INTRODUCTION: Rehospitalization early post-kidney transplant is common and has a
      negative impact in morbidity, graft survival, and health costs. Infection is one
      the most common causes, and identifying the risk factors for early readmission
      due to infectious complications may guide a preventive program and improve
      outcome. The aim of this study was to evaluate the incidence, characterize the
      population, and identify the risk factors associated with early readmission for
      infectious complications post-kidney transplantation. METHODS: We performed a
      retrospective cohort study of all the kidney transplants performed during 2015.
      The primary outcome was readmission in the first 3 months post-transplant due to
      infectious causes defined by clinical and laboratory parameters. RESULTS: We
      evaluated 141 kidney transplants; 71% of subjects were men, with an overall mean
      age of 50.8 +/- 15.4 years. Prior to transplant, 98% of the patients were
      dialysis dependent and 2% underwent pre-emptive living donor kidney transplant.
      The global readmission rate was 49%, of which 65% were for infectious
      complications. The most frequent infection was urinary tract infection (n = 28,
      62%) and the most common agent detected by blood and urine cultures was
      Klebsiella pneumonia (n = 18, 40%). The risk factors significantly associated
      with readmission were higher body mass index (P = .03), diabetes mellitus (P =
      .02), older donor (P = .007), and longer cold ischemia time (P = .04). There were
      3 graft losses, but none due to infectious complications. CONCLUSION: There was a
      high incidence of early rehospitalization due to infectious complications,
      especially urinary tract infections to nosocomial agents. The risk factors
      identified were similar to other series.

PMID- 28457395
TI  - Fibrogenesis in Kidney Transplant: Dysfunction Progress Biomarkers.
AB  - INTRODUCTION: Fibrogenesis markers, such as alpha-actin (AA), CD163
      (macrophages), and E-cadherin, have been studied as chronic kidney allograft
      injury (CAI) predictors, a major cause of allograft failure. OBJECTIVE:
      Investigate the value of these markers in predicting CAI and initiation of
      dialysis. MATERIALS AND METHODS: Retrospective analysis of 26 kidney allograft
      biopsies (from 22 patients with CAI) during 2 years, evaluating intensity and
      percentage of marked cells on glomeruli and tubulointerstitial compartment. At
      the time of the biopsy, patients were 45.5 +/- 15.8 years and 4.2 years after
      transplant, and they had a mean glomerular filtration rate (GFR) of 25.8 +/- 9.9
      mL/min. From an average of 8.5 glomeruli per biopsy, there was <=25% sclerosis in
      17 cases, 26% to 50% in 5, and >50% in 4. Interstitial fibrosis or tubular
      atrophy affected <=25% of cortical area in 14 cases, 26% to 50% in 8, and >50% in
      2. Twelve patients started dialysis 5.8 +/- 4.7 years after transplant, with an
      average GFR 20.9 mL/min at the time of the biopsy. RESULTS: There was a higher
      intensity and percentage of CD163-marked cells in the tubulointerstitial
      compartment in advanced interstitial fibrosis. We found an association between
      intensity of AA in the tubulointerstitial compartment and initiation of dialysis
      (P = .003) and a negative correlation between intensity of E-cadherin loss and
      GFR (r = -0.56, P = .012). CONCLUSIONS: In our study, intensity of
      tubulointerstitial AA was shown to be a predictor of initiation of dialysis, and
      E-cadherin loss intensity was associated to CAI progression. However, prospective
      and larger studies are needed to evaluate the predictive value of these markers.

PMID- 28457396
TI  - Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic
      Correlates in a 10-year Retrospective Study.
AB  - INTRODUCTION: There is a high incidence of nephrotic proteinuria in renal
      transplant recipients, which is an accurate predictor of graft loss. Despite
      this, its histologic correlates and prognostic implications are still not well
      characterized. We assessed the clinical and histological correlates of kidney
      transplantation patients with nephrotic range proteinuria. METHODS: We have
      retrospectively analyzed clinical and histological data from 50 kidney
      transplantation biopsy specimens from 44 renal transplant recipients with
      nephrotic range proteinuria between 2006 and 2015. The median follow-up time was
      93 months (range, 14 months to 190 months). RESULTS: The mean age of the patients
      was 45.2 +/- 13.7 years and our cohort included 86% recipients of deceased-donor
      grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors
      in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The
      average proteinuria was 6.9 +/- 3.8 g/d and 52% of patients presented with
      nephrotic syndrome. The main histological findings were transplant glomerulopathy
      (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%).
      Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy
      specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no
      statistically significant difference between the histologic diagnosis nor the
      proteinuria levels and the outcome of the graft. CONCLUSIONS: The main causes of
      nephrotic range proteinuria in patients undergoing biopsy were transplant
      glomerulopathy, recurrence of the underlying disease, and de novo
      glomerulonephritis. Nephrotic range proteinuria was related to a high rate of
      graft loss.

PMID- 28457397
TI  - Parathyroidectomy in Persistent Post-transplantation Hyperparathyroidism - Single
      center Experience.
AB  - BACKGROUND: Hyperparathyroidism is a common complication in chronic kidney
      disease and might persist in up to 25% of patients after transplantation. In this
      setting, vitamin D analogues further aggravate persistent hypercalcemia and
      cinacalcet has not been approved for these patients, some of whom will require
      parathyroidectomy to correct post-transplantation hyperparathyroidism.
      OBJECTIVES: In this single-center, retrospective study we aimed to analyze the
      long-term effect of parathyroidectomy on calcium, phosphorus, and parathyroid
      hormone (PTH) levels and its effect on allograft function in kidney
      transplantation patients submitted to parathyroidectomy. PATIENTS AND METHODS:
      Fifteen patients underwent parathyroidectomy between January 2005 and January
      2015; median age 54 years old; 8 (53.3%) were receiving cinacalcet at the time of
      surgery. Pre-parathyroidectomy median values of intact PTH, calcium, and
      phosphorus were, respectively, 262 pg/mL, 10.8 mg/dL, and 2.4 mg/dL. Surgery
      consisted of uniglandular parathyroidectomy in 5 (33.3%) patients, biglandular in
      4 (26.7%), and subtotal in 6 (40%). There was no surgery-related mortality.
      RESULTS: Compared with baseline, there was a decrease of PTH (262 pg/mL vs. 106
      pg/mL, P = .001), calcium, and phosphorus levels (10.8 mg/dL vs. 10.4 mg/dL, P =
      .3; 2.4 vs. 2.9 mg/dL, P = .05) 1 year after surgery; with normalization of serum
      calcium at the end of follow-up (10.8 mg/dL vs. 9.4 mg/dL, P = .04). A decrease
      in estimated glomerular filtration rate occurred 1 month post-surgery (62.7 mL/m
      vs. 49.7 mL/m, P = .006) but returned to baseline 1 year after surgery (62.7 mL/m
      vs. 60.8 mL/m, P = .73). CONCLUSION: Parathyroidectomy appears to be a safe
      procedure and should be considered in kidney transplantation patients with
      persistent post-transplantation hyperparathyroidism. Although there was an acute
      estimated glomerular filtration rate decrease, we observed no long-term
      deterioration in allograft function.

PMID- 28457398
TI  - Serum Magnesium and Related Factors in Long-Term Renal Transplant Recipients: An
      Observational Study.
AB  - BACKGROUND: Low serum magnesium (MgS) is a known risk factor for cardiovascular
      and mineral bone disease. In renal transplant recipients (RTRs), low MgS levels
      have been related to higher glomerular filtration rates (GFR) and with
      calcineurin inhibitors, particularly tacrolimus. We aimed to evaluate MgS in
      renal transplant recipients with over 1 year of follow-up to establish related
      risk factors and the impact of the use of cyclosporine versus tacrolimus.
      METHODS: Cross-sectional study of 94 RTRs with more than 12 months of follow-up.
      Hypomagnesemia was defined as serum magnesium level <1.5 mg/dL. RESULTS:
      Hypomagnesemia was found in 5.3% of patients. MgS showed a negative correlation
      with creatinine clearance. A positive correlation between MgS with urinary
      magnesium and phosphorus was found. Cyclosporine versus tacrolimus analysis did
      not show a significant difference regarding MgS when considering all the
      population and the subgroup of patients with GFR >45 mL/min/1.73 m2. On the
      subgroup with GFR <45 mL/min/1.73 m2, those on tacrolimus had lower MgS than
      those on cyclosporine, but those same patients presented with significantly
      different GFR, higher in the tacrolimus subgroup. CONCLUSIONS: Hypomagnesemia has
      a low prevalence in RTRs with more than 1 year of follow-up. MgS levels evidenced
      a strong correlation with GFR. A significant difference on MgS levels between
      patients on tacrolimus and cyclosporine was found only when considering GFR <45
      mL/min/1.73 m2, in which patients on tacrolimus had significantly higher GFR than
      patients on cyclosporine, which may explain these results.

PMID- 28457399
TI  - Polyomavirus Nephropathy: Ten-Year Experience.
AB  - BACKGROUND: Polyomavirus nephropathy (BKVN) is an important cause of chronic
      allograft dysfunction (CAD). Recipient determinants (male sex, white race, and
      older age), deceased donation, high-dose immunosuppression, diabetes, delayed
      graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are
      risk factors. Reducing immunosuppression is the best strategy in BKVN. The
      objective of our study was to evaluate CAD progression after therapeutic
      strategies in BKVN and risk factors for graft loss (GL). METHODS: Retrospective
      analysis of 23 biopsies, from patients with CAD and histological evidence of
      BKVN, conducted over a period of 10 years. Glomerular filtration rate was <30
      mL/min in 16 patients at the time of the BKVN diagnosis. RESULTS: BKVN was
      histologically diagnosed in 23 recipients (19 men, 4 women). All patients were
      white, with age of 51.2 +/- 12.1 years (6 patients, age >60 years), and 22 had a
      deceased donor. Diabetes affected 4 patients, DGF occurred in 3, cytomegalovirus
      infection in 2, and AR in 15. All patients were medicated with calcineurin
      inhibitors (CNI) (95.7% tacrolimus) and corticoids, and 16 also received an
      antimetabolite. One year after antimetabolite reduction/discontinuation and/or
      CNI reduction/switching and/or antiviral agents, graft function was decreased in
      11 patients, increased/stabilized in 10, and unknown in 2. GL occurred in 9
      patients. Older age (hazard ratio, 1.76; 95% confidence interval, 0.94-3.28) and
      DGF (hazard ratio, 2.60; 95% confidence interval, 0.54-12.64) were the main risk
      factors for GL. The lower GFR at the time of the BKVN diagnosis was associated
      with an increased risk of initiation of dialysis. CONCLUSIONS: GL occurred in
      39.1% of patients with BKVN and DGF; older age and lower GFR at the time of
      diagnosis were important risk factors. Early diagnosis of BKVN is essential to
      prevent GL.

PMID- 28457401
TI  - Spironolactone in Post-Transplant Proteinuria: A Safe Alternative Therapy.
AB  - BACKGROUND: Aldosterone is involved in the process of renal allograft fibrosis,
      clinically manifest by proteinuria and allograft dysfunction, with increased risk
      for cardiovascular death. The treatment with aldosterone antagonists appears to
      be effective in controlling proteinuria, with a protective effect on progression
      of renal fibrosis. METHODS: This retrospective, cohort study included kidney
      transplant recipients from January 1993 to June 2015. Inclusion criteria were
      persistent proteinuria >0.5 g/d, longer than 6 months, and spironolactone
      therapy. RESULTS: One hundred forty transplant recipients fulfilled the inclusion
      criteria and were divided into 3 groups, according to proteinuria levels at the
      beginning of spironolactone therapy: low (<1 g/24 h), intermediate (1-3 g/24 h),
      and nephrotic (>3 g/24 h). Groups were comparable in demographic data, with a
      higher incidence of living related donors in the nephrotic group. In patients
      with proteinuria >=1 g/d, we observed a significant reduction in proteinuria
      after 6 months of therapy that persisted over time. Blood pressure and glomerular
      filtration rate persisted stable over time. Adverse events were not severe to
      withdrawal therapy. CONCLUSIONS: Spironolactone can be a safe alternative to
      control post-transplant proteinuria, especially in patients with mild to moderate
      allograft dysfunction with proteinuria >=1 g/day.

PMID- 28457400
TI  - Prostate Cancer in Renal Transplant Recipients: Diagnosis and Treatment.
AB  - BACKGROUND: We currently know that prostate cancer (Pca) risk is reduced in
      patients undergoing kidney transplantation. However, its impact and treatment are
      not widely studied. METHODS: This was a retrospective study of male patients
      submitted to kidney transplantation in our center from 1980 to 2016 evaluating
      incidence, treatment, and follow-up of Pca in our population. RESULTS: In 1805
      patients undergoing kidney transplantation, 20 men were diagnosed with Pca,
      leading to an incidence of 1.1%. Median age at renal transplantation was 53.4
      years with a median age at diagnosis of Pca of 61.2 years. Initial median
      prostate-specific antigen (PSA) was 6 ng/mL and Gleason score was 7 (3 + 4) in
      about 50% of cases. Bone metastasis developed in 10% and no visceral metastases
      were diagnosed. The majority of patients were submitted to radical prostatectomy
      and bilateral pelvic lymph node dissection. Some other cancers occurred in these
      patients such as skin and pulmonary cancers. In 35% of the cases, the graft was
      lost. The main cause of patient death was cardiovascular. The mean graft survival
      was about 14 years. The majority of patients are alive with functioning grafts
      (65%). CONCLUSION: In our center the clinical incidence of Pca in patients
      undergoing kidney transplantation is 1.1% and surgical treatment seems to be a
      good initial option.

PMID- 28457402
TI  - Early Vascular Thrombosis After Kidney Transplantation: Can We Predict Patients
      at Risk?
AB  - BACKGROUND: Renal transplant is the therapy of choice for patients with chronic
      renal disease. In recent years, improvement in immunosuppressive drugs reduced
      early graft loss associated with acute rejection. However, vascular thrombosis,
      accounting for 5% of early graft loss, can sensitize the recipient for human
      leukocyte antibodies, reducing the chance for a second transplant. The aim of
      this study was to identify risk factors for vascular thrombosis in a single
      transplant center, to design specific prevention protocol. METHODS: This was a
      retrospective, case-control study. From the Renal Transplant Unit database, we
      identified 21 cases of vascular thrombosis in recipients of kidneys from deceased
      donors. Recipients from the contralateral kidney from the same donor, without
      vascular complications, were assigned to the control group. Data analyzed
      included donor, recipient, transplant surgery, and post-operative follow-up. The
      local ethics committee approved the protocol. RESULTS: Thrombosis and control
      groups were comparable for recipient characteristics, cold ischemia time, organ
      side (right or left), and site of arterial anastomosis. We observed an increased
      risk for vascular thrombosis in kidneys with multiple veins (odds ratio, 11.32; P
      = .03). Organ retrieval surgery complications, such as vascular lesions or
      heterogeneous perfusion, despite normal pre-implantation biopsy, were considered
      risk factors for vascular thrombosis within the first post-operative day (odds
      ratio, 7.1; P = .03). CONCLUSIONS: In this series, multiple renal vein and organ
      retrieval surgery complications were risk factors for early vascular thrombosis.

PMID- 28457403
TI  - Surgical Complications in Early Post-transplant Kidney Recipients.
AB  - BACKGROUND: The purpose of this study was to determine the incidence of early
      surgical complications of kidney transplantation in our institution and its
      association with donor and recipient factors, as well as patient and transplant
      outcome. METHODS: A retrospective cohort study of all kidney transplants
      performed during 2015 was made. We evaluated the incidence of surgical
      complications and the outcome of patients and grafts at a 3-month follow-up
      interval. RESULTS: During the study period, 141 kidney transplants occurred.
      Seventeen patients had surgical complications (6 urologic, 6 vascular, and 5
      other complications). Five patients lost the graft during the follow-up. Older
      age was associated with other surgical complications (P = .023), and graft loss
      was associated with the existence of surgical complications, namely, vascular
      complications (P <.001). For both surgical complications in general and urologic
      complications, a statistically significant relationship was found with patient
      weight (P = .003 and P = .034, respectively). The correlation between body mass
      index (BMI) and surgical complications was not statistically significant.
      CONCLUSIONS: Our study reveals that older and heavier patients have a higher risk
      of surgical complications and that vascular complications are associated with
      graft loss. A statistically significant relationship was not found between BMI
      and surgical complications, which could indicate that BMI is not the ideal
      obesity marker. The incidence of surgical complications found in our study is
      similar to the literature. The selection of transplant recipients is a difficult
      task, and the possibility of additional surgical complications in older and
      overweight patients should be taken into account.

PMID- 28457405
TI  - Diaphragm Muscle Surface Electromyography in Patients Submitted to Liver
      Transplant and Eligible for Extubation.
AB  - INTRODUCTION: Liver disease induces many organic and metabolic changes, leading
      to malnutrition and weight and muscular function loss. Surface electromyography
      is an easily applicable, noninvasive study, through which the magnitudes of the
      peaks on the charts depict voluntary muscle activity. AIM: To evaluate the
      diaphragmatic surface electromyography of postoperative liver transplantation
      subjects. METHODS: Subjects were patients who underwent liver transplantation and
      extubation in the Clinical Hospital of State University of Campinas.
      Electromyography data were collected with support pressure of <=10 cm H2O,
      Glasgow Coma Scale = 11, and minimum dosages of vasoactive drugs, and data were
      collected again 30 minutes after extubation. Signal collection was performed with
      sEMG System Brazil SAS1000V3 electromyograph and electrode stickers. Statistical
      analysis was performed using R software. RESULTS: The average time of surgery was
      345.36 +/- 125.62 minutes. Time from spontaneous mode until extubation was 417.14
      +/- 362.97 minutes. The RMS (root mean square) values of the right and left domes
      in spontaneous mode with minimal ventilation parameters were 26.68 +/- 10.92 and
      26.55 +/- 10.53, respectively, and the RMS values after extubation were 31.93 +/-
      18.69 to 34.62 +/- 13.55, for right and left domes. The last calculated
      pretransplant Model for End-stage Liver Disease score averaged 19.64 +/- 8.41.
      CONCLUSION: There were significant differences between the RMS of the diaphragm
      domes under mechanical ventilation and after extubation, showing lower
      effectiveness of the diaphragm muscle against resistance, without the aid of
      positive pressure and the existing overload of the left dome.

PMID- 28457404
TI  - Lung Ultrasound and Pulmonary Function Test in Cirrhotic Patients.
AB  - Lung ultrasound (LU) is useful in the diagnosis of pulmonary interstitial
      alveolar syndrome (IAS) when B-lines are detected. Its prevalence and effect in
      lung function is not well studied in cirrhotic patients. The objective of this
      study was to detect the prevalence of interstitial-alveolar involvement with LU
      and correlate with pulmonary function test to distinguish the effect of ascites
      and B-lines in pulmonary function. This was an observational single-center study
      with 49 patients listed for liver transplantation submitted for LU and pulmonary
      function tests. Patients were divided into 4 groups: no ascites and no B-lines (n
      = 19), B-lines only (n = 19), ascites only (n = 6), and ascites and B-lines (n =
      5). There was a worse forced vital capacity (FVC) in patients with B-lines only
      (76.1% +/- 9.2; P = .0058) and ascites only (66.8% +/- 10.2; P = .0010). 1-second
      forced expiratory volume (FEV1) also was lower in patients with B-lines only
      (78.5% +/- 10.3; P = .0001), ascites only (71.3% +/- 13.2; P = .0004), and B
      lines and ascites (74.2% +/- 7.6; P = .0035). Model for End-Stage Liver Disease
      score was worse in the group with ascites and B-lines (22.4 +/- 10.1; P = .0229).
      B-Lines reduced FVC and FEV1 in our study and may be an independent factor in
      worsening pulmonary function in these patients.

PMID- 28457406
TI  - Comparison of the Results of Living Donor Liver Transplantation Due to Acute
      Liver Failure and Biliary Atresia in a Quaternary Center.
AB  - OBJECTIVE: The objective of this study was to compare the complications,
      outcomes, and survival prevalence in patients undergoing living donor liver
      transplantation due to biliary atresia (BA) or acute liver failure (ALF).
      RESULTS: In the period of June 1998-July 2016, 199 children underwent living
      transplantation due to BA or ALF. Of these 199, 184 were included in the
      analysis. The average age, weight, and body mass index of BA patients were lower
      than those of ALF (P < .001). The chi-square test showed a higher prevalence of
      infection in transplant recipients due to BA (P = .0001) and a higher prevalence
      of hepatic artery stenosis in those who underwent transplantation due to ALF (P =
      .001). In the multivariate analysis, the infection remains statistically more
      prevalent in the BA group (95% confidence interval [CI], 0.20-0.60), while
      hepatic artery stenosis loses significance. The mortality rate was similar in
      both groups and the survival in 5 years also. The prevalence of hepatic artery
      thrombosis, portal vein thrombosis/stenosis, biliary stenosis, and acute and
      chronic cellular rejection showed no statistical difference between the two
      groups. CONCLUSION: Living donor liver transplantation should be a valid option
      in cases of fulminant hepatitis with an indication for liver transplantation,
      especially in places where the number of cadaverous donors is low and the length
      of time on the waiting list is high.

PMID- 28457407
TI  - Oral Health and Quality of Life in Candidates for Liver Transplantation.
AB  - BACKGROUND: There is a gap in the scientific literature about the association
      between oral health and the health-related quality of life of patients on the
      liver transplantation waiting list. The aim of this work was to describe aspects
      of oral health and quality of life of patients on a liver transplantation waiting
      list. METHODS: This was a cross-sectional study among 116 patients with chronic
      hepatic disease: 29 on a liver transplantation waiting list (Model for End-Stage
      Liver Disease score >=15) and 87 under monitoring in a gastroenterology service
      in a Brazilian university hospital. Oral health was evaluated according to
      criteria recommended by the World Health Organization and by the European
      Association of Dental Public Health. Health-related quality of life was evaluated
      by means of the 36-Item Short-Form Health Survey (SF-36). RESULTS: Patients on
      the liver transplantation waiting list presented poorer health-related quality of
      life than those who were not on the list in the domains physical functioning,
      role physical, bodily pain, general health perceptions, and social functioning
      and in the physical component summary. Periodontitis affected 72.4% of the
      patients on the liver transplantation waiting list, but only 27.6% of the
      patients not on that list. Reduced salivary flow was associated with poorer
      mental health component summary in hepatitis C patients. CONCLUSIONS: Patients on
      the liver transplantation waiting list presented poorer health-related quality of
      life than those who were not on the list, mainly in the indicators concerning
      physical health, as well as higher frequencies of decayed teeth and
      periodontitis. The mental health component summary was associated with reduced
      salivary flow in hepatitis C patients.

PMID- 28457408
TI  - Hepatic Transplants in Espirito Santo State, Brazil.
AB  - BACKGROUND: The Meridional Hospital Liver transplant unit is the only one active
      in all Espirito Santo State, Brazil, since 2004. OBJECTIVE: The aim is to analyze
      data of the first 250 transplants performed by the team. METHODS: This
      retrospective study reviewed files from patients transplanted in the Meridional
      Hospital from January 2005 to December 2015. RESULTS: There were 250 liver
      transplants in 236 patients and 14 retransplants. 72.4% were male recipients,
      with average age of 51.1 years (1-70 years), and the main etiology was alcoholic
      cirrhosis (33.6% of the cases). Surgical reintervention occurred in 58 patients
      (include retransplantations) during the same hospitalization, with revision of
      homeostasis and retransplant as main indications. In the retransplant group,
      73.3% of patients died within 2 months. Thrombosis of the hepatic artery was
      responsible for 40% of the indications for retransplant. The average time between
      first and second transplant was 223 days (median 14 days). Currently 152 of 236
      patients are living, with 1-year life expectancy of approximately 71%. The
      mortality peak occurred from the immediate postoperative period to 2 months post
      transplant (63.8% of the deaths). 32% of subjects did not need intraoperative
      blood transfusion. The average time of intensive care unit stay was of 8.52 days,
      and overall hospital stay was 21.7 (median 15 days). CONCLUSION: Despite the
      logistic difficulties and lack of donors our unit, keep in advance with survival
      comparable to other national centers (68% to 74% in 1-year).

PMID- 28457409
TI  - One Hundred Consecutive Liver Transplants Using Institutes Georges Lopez-1
      Preservation Solution: Outcomes and Prognostic Factors.
AB  - BACKGROUND: There are only 4 prior studies reporting on outcomes of liver
      transplantation (LT) using Institutes Georges Lopez-1 (IGL-1) preservation
      solution. Detection of negative predictors of LT using IGL-1 may help finding
      strategies to protect selected recipients at higher risk of graft failure and
      death. METHODS: Review of all consecutive adult patients who underwent a first
      whole-graft LT using IGL-1 at authors' institution from 2013 to 2016. Primary end
      point was graft failure within the first 90 postoperative days (PODs). Graft
      losses due to any cause (including all deaths with a functioning graft) were
      recorded as graft failures. RESULTS: Of all 100 patients included in this study,
      37 were women; median age was 58 years (range 18-71). There were 12 graft losses
      during the first 90 PODs (including 3 cases of primary nonfunction of the liver
      allograft), and 10 of the 12 graft losses occurred on first 30 PODs. All 12
      patients who experienced graft loss (including 1 patient who underwent liver
      retransplantation) died within the first 90 PODs. Of the total 100 patients, 14
      experienced biliary complications. Univariate analysis revealed prolonged warm
      ischemic time (WIT) as the only predictor of 90-day graft failure (odds ratio =
      23.5, confidence interval = 1.29-430.18, P = .03). The cutoff by receiver
      operating characteristic curve for WIT was 38 minutes (area under the curve =
      0.70). Positive predictive value for WIT >38 minutes was 94.3%. CONCLUSIONS: LT
      using IGL-1 can be performed safely. Similar to prior reports on LT using other
      preservation solutions, prolonged WIT was associated with adverse outcomes.

PMID- 28457410
TI  - Immunomodulation, Acute Renal Failure, and Complications of Basiliximab Use After
      Liver Transplantation: Analysis of 114 Patients and Literature Review.
AB  - Basiliximab is considered to be effective in preventing cellular rejection (CR)
      in solid organ transplantation and is commonly used for renal transplants. The
      aim of this study was describe the population of patients undergoing orthotopic
      liver transplantation (LT) receiving basiliximab in the period 2012-2016 in the
      liver transplant service at the State University of Campinas, Sao Paulo, Brazil.
      We analyzed 114 patients who underwent LT and received basiliximab; 83 (72.8%)
      were male and 31 (27.2%) female, with an overall mean age of 54.3 years.
      Immunosuppression was performed with corticosteroids during anesthetic induction,
      and postoperatively with tacrolimus in 85.5%, sodium mycophenolate in 81.7%,
      cyclosporine in 12.7%, and everolimus in 15.5% of patients. CR was observed in
      25.43% of patients, confirmed by biopsy in 15 patients: 50% acute CR, 21.42% late
      acute CR, and 28.57% chronic CR. Thus, the data are consistent with the
      literature regarding the benefit of using basiliximab as induction therapy while
      reducing the incidence of CR after LT, but on univariate analysis to evaluate
      factors associated with the occurrence of CR, the analyzed variables did not
      present statistical significance. There was acute renal failure (ARF) in 46.84%
      of patients and hemodialysis was performed in 20% of cases. In a previous series
      in our service, there was an ARF rate of 50%, so the incidence reduction of ARF
      after basiliximab use was 3.16%. Moreover, there was 6.95% hepatic artery
      thrombosis, 2.6% portal vein thrombosis, 2.6% biliary fistulas, 17.4% pneumonia,
      and 3.4% sepsis, which did not differ from the literature or from our earlier
      study without the use of basiliximab, suggesting the safety of this medication.
      In conclusion, in this series, basiliximab influenced the decrease of the CR
      incidence with no proven benefit on improvement in the ARF.

PMID- 28457411
TI  - Immunoexpression of Heat Shock Protein 70, Glypican 3, Glutamine Synthetase, and
      Beta-Catenin in Hepatocellular Carcinoma After Liver Transplantation: Association
      Between Positive Glypican 3 and Beta-Catenin With the Presence of Larger Nodules.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the 6th leading cause of cancer
      worldwide. Its recurrence ranges from 6% to 26%. In the literature, many factors
      are associated with higher risk of recurrence, without a clear definition of the
      best method that could predict this highly lethal event. OBJECTIVE: The aim of
      this study was to evaluate the immunoexpression of immunohistochemical markers:
      HSP70, glypican 3, glutamine synthetase, and beta-catenin, as well as studying
      their association with tumor characteristics and prognosis of patients undergoing
      liver transplantation for HCC. METHODS: We studied 90 patients who underwent
      liver transplantation from 1998 to 2012. Afterwards we evaluated factors related
      to survival, tumor recurrence, and the correlation of expression of the
      immunohistochemical markers. RESULTS: Immunohistochemical marker glutamine
      synthetase showed a positive trend toward better survival. HSP70-positive
      patients had a higher prevalence of histologic grade III. Patients with positive
      glypican 3 showed larger lesions and a higher number with AFP >200 ng/mL.
      Patients with positive beta-catenin showed larger nodules and more with
      histologic grade III. The association between beta-catenin and glypican 3 showed
      positive association with larger nodules. CONCLUSIONS: Most of the markers
      studied had a correlation with at least one of the variables studied, confirming
      our hypothesis that these markers can indeed assist in assessing the prognosis of
      patients undergoing liver transplantation for HCC.

PMID- 28457412
TI  - Factors Related to Hepatocellular Carcinoma Recurrence After Liver
      Transplantation-A Brazilian Multicenter Study.
AB  - BACKGROUND: Liver transplantation (LT) is a curative treatment option for
      hepatocellular carcinoma (HCC); recurrent HCC after liver transplantation (HCC-R)
      is diagnosed in 9%-16%. The objective of this study was to evaluate which factors
      are associated with R-HCC after liver transplantation. METHODS: This
      retrospective real-life study analyzed 278 LTs from 3 reference centers (2,093
      LTs) in Brazil from 1988 to 2015. HCC-R with histologic confirmation was seen in
      40 patients (14.4%). RESULTS: Most of them were male with cirrhosis secondary to
      viral hepatitis. Only 37.5% underwent chemoembolization, and 50% had cold
      ischemia time >8 hours. From the explant analysis, most of the patients were
      outside Milan criteria and 37.5% had microvascular invasion. The donors were
      mostly male, and the median intensive care unit time was >3 days. The Kaplan
      Meier survival was lower according to alpha-fetoprotein (AFP) >200 ng/dL (P =
      .02), and older donors and more blood transfusions were risk factors for HCC-R
      death. CONCLUSION: AFP >200 ng/mL was associated with lower survival, and older
      donors and more blood transfusions were risk factors for death after HCC-R. A
      trend to lower survival was observed in patients who did not have
      chemoembolization and had cold ischemia times >8 hours.

PMID- 28457413
TI  - Hepatic Artery Thrombosis After Liver Transplantation: Five-Year Experience at
      the State University of Campinas.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) is reported in 4%-15% of orthotopic
      liver transplants. Risk factors include technical error in the anastomosis,
      vascular anatomic variation, and high microvascular resistance. The aim of this
      study was to verify the incidence of HAT, early or late, and possible risk
      factors. METHODS: This was a retrospective study from January 2007 to December
      2012 at the State University of Campinas. Variables analyzed were age, sex, cold
      and warm ischemia times, underlying disease, presence of hepatocellular
      carcinoma, Model for End-Stage Liver Disease (MELD) score, arterial anatomic
      variation in the graft, cytomegalovirus (CMV) infection, rejection, biliary
      complications, retransplantation rate, and survival. RESULTS: The incidence of
      HAT was 21/263, or 7.9%. Pure average MELD score was 22 +/- 7.4. There was
      vascular anatomic variation in the graft in 14.2% of cases, in the majority
      (66.6%) a right hepatic artery from the superior mesenteric artery, and 4.76% of
      patients had CMV infection and acute cellular rejection (1 case each). There were
      biliary complications in 38% of patients, 13.3% of cases in patients with early
      HAT, and 100% of patients with late HAT (P = .002). Body mass index in late HAT
      was higher (P = .01). CONCLUSIONS: Late HAT was related to a significant increase
      in biliary complications (stenosis), and the survival rate was similar at 5
      years.

PMID- 28457414
TI  - Pre-emptive Therapy for Cytomegalovirus in Post-transplantation Liver Patients
      With Donor-Positive/Recipient-Negative Serostatus.
AB  - INTODUCTION: Infection by cytomegalovirus (CMV) is a major cause of morbidity
      among immunosuppressed patients, especially after solid organ transplantation.
      The risk of CMV after organ transplantation is strongly related to the serology
      of the donor and the recipient. The objective of this study was to analyze the
      outcomes and costs of pre-emptive therapy in patients after liver transplantation
      with donor-positive/recipient-negative (D+/R-) serostatus. METHODS: This
      retrospective study analyzed all patients who underwent liver transplantation
      with CMV serostatus D+/R- between January 2012 and December 2015. The service
      protocol adopts pre-emptive therapy. The outcomes and costs of this therapy are
      described. RESULTS: Of the 119 patients undergoing liver transplantation, 19 were
      D+/R- and entered the main analysis. Of these, 7 had positive polymerase chain
      reaction (PCR) results, and 1 developed CMV disease. Of the 6 patients who
      received no treatment, none developed CMV disease. Analyzing costs, pre-emptive
      therapy for these patients generated service savings of R$32,346.00. CONCLUSIONS:
      Although outcomes of universal prophylaxis and pre-emptive therapy are similar,
      pre-emptive therapy save on costs and have to be considered in patients with high
      risk CMV disease after liver transplantation.

PMID- 28457415
TI  - Clinical and Nutritional Factors Associated With Early Mortality After Heart
      Transplantation.
AB  - OBJECTIVE: The aim of this work was to verify the association between clinical
      and nutritional factors and mortality in the 1st 30 days after heart
      transplantation. METHODS: This was a retrospective study of patients who
      underwent heart transplantation in a public hospital in Brazil from January 2013
      to August 2015. The clinical and nutritional factors analyzed were: body mass
      index, body surface area, cachexia, infection, duration of orotracheal
      intubation, ejection fraction, mean pulmonary pressure, Interagency Registry for
      Mechanically Assisted Circulatory Support (INTERMACS) score, hemoglobin, and
      diabetes mellitus. The primary outcome was mortality in the 1st 30 days after
      heart transplantation, and secondary outcomes were infection, acute kidney
      insufficiency, and duration of orotracheal intubation. We performed chi-square
      test, unpaired t test, and logistic regression in the analyses. A P value of <
      .05 was considered to be significant. RESULTS: The sample had 103 patients, of
      which 16 patients (15.53%) died within 30 days after heart transplantation. We
      observed a relationship between death and orotracheal intubation duration (P <
      .01), postoperative creatinine (P < .01), acute kidney injury (P < .01), and
      INTERMACS score (P = .01) in the bivariate analysis but not in the multivariate
      model. CONCLUSIONS: Clinical and nutritional factors had no impact on mortality
      up to 30 days after heart transplantation in this study, although orotracheal
      intubation duration, postoperative creatinine, acute kidney injury, and INTERMACS
      score were individually associated with early death.

PMID- 28457416
TI  - Abdominal Complications After Lung Transplantation in a Brazilian Single Center.
AB  - Surgical and nonsurgical abdominal complications have been described after lung
      transplantation. However, there is limited data on this event in this population.
      The objective of this study was to analyze the incidence of abdominal
      complications in patients undergoing lung transplantation at the Heart Institute
      of the Faculty of Medicine, University of Sao Paulo (InCor-HCFMUSP) between the
      years 2003 and 2016. The main causes of abdominal complications were inflammatory
      acute abdomen (7 patients; 14%), obstructive acute abdomen (9 patients; 18%),
      gastroparesis (4 patients; 8%), distal intestinal obstruction syndrome (4
      patients; 8%), perforated acute abdomen (7 patients; 14%), cytomegalovirus (CMV;
      6 patients; 12%), and other reasons (12 patients; 26%). Separating these patients
      according to Clavien-Dindo classification, we had 21 patients (43%) with
      complications grade II, 4 patients (8%) with complications grade IIIa, 7 patients
      (14%) with grade IIIb complications, 7 patients (14%) with grade IV
      complications, and 10 patients (21%) with grade complications V. In conclusion,
      abdominal disorders are seriously increased after lung transplantation and
      correlate with a high mortality. Early abdominal surgical complication has worse
      prognosis.

PMID- 28457417
TI  - Incidence and Mortality by Cancer in Patients After Lung Transplantation in a
      Brazilian Institution.
AB  - BACKGROUND: The first human lung transplantation was performed by James Hardy in
      1963 due to lung cancer. Currently, malignancy has its importance in the follow
      up of transplanted patients because cancer risk is higher in this population and
      the main risk factor for this augmentation is immunosuppression. The most common
      types of cancer are non-melanoma skin cancer and post-transplantation
      lymphoproliferative diseases. The objective of this study is to measure the
      cancer incidence and its related mortality in lung-transplanted patients of a
      Brazilian institution. METHODS: Review of the records of the 263 patients who
      underwent lung transplantation between April 2000 and April 2016 at the Heart
      Institute (InCor), focusing on the incidence of cancer, most common types of
      malignancies, and cancer mortality rate. We compared incidence and mortality with
      the International Society for Heart and Lung Transplantation (ISHLT) database.
      RESULTS: During the 16-year period, the total incidence of cancer was 10.3% with
      27 cases diagnosed in 21 patients. The most common types of cancer were non
      melanoma skin cancer, prostate cancer, and post-transplantation
      lymphoproliferative diseases. Comparing the incidences after 1-year, 5-year, and
      10-year follow-up with the ISHLT database, they were similar in the first two
      periods and higher in the third period. As to cancer mortality rate, it was
      similar to the ISHLT database in both periods analyzed. CONCLUSION: The incidence
      of malignancies was higher in our transplanted patients in comparison with the
      Brazilian population, and the most frequent types of cancer are in accordance
      with the literature, except for prostate cancer. Cancer mortality rate was
      similar to that from the ISHLT database.

PMID- 28457419
TI  - Relevance of Chimerism Analysis After Allogeneic Stem Cell Transplantation.
AB  - Hematopoietic stem cell transplantation is a potentially curative therapy for a
      range of malignant and non-malignant hematological diseases. Analysis of
      chimerism following allogeneic stem cell transplantation has been a routine
      method for the assessment of engraftment and early detection of graft failure.
      Lineage-specific chimerism monitoring is progressively used to specifically
      detect chimerism in one or more cell subsets, which may be undetected in
      assessment of the whole leukocyte population. The chimerism study in different
      leukocyte subpopulations increases sensitivity and specificity in the monitoring
      after transplantation, especially the analysis of T lymphocytes. All peripheral
      blood samples were separated into mononuclear cells and granulocytes by Ficoll
      density gradient centrifugation and T, B, and CD34+ was separated by
      immunomagnetic automatic cell separator. After DNA extraction, chimerism
      monitoring was performed using short tandem repeat by multiplex polymerase chain
      reaction followed by capillary electrophoresis. Quantification of chimerism was
      performed by determining the ratio of peak areas from donor and recipient
      informative short tandem repeat. Donor-recipient chimerism analysis in patients
      after allogeneic stem cell transplantation is a practical, feasible, and useful
      tool that predicts clinical outcomes and provides a guide for suitable
      therapeutic interventions.

PMID- 28457418
TI  - Histopathological Findings Associated With Gastroesophageal Reflux Disease and
      Aspiration After Lung Transplantation: Initial Brazilian Single-Center
      Experience.
AB  - BACKGROUND: Gastro-esophageal reflux disease (GERD) and broncho-aspiration (BA)
      are known to increase the risk for chronic lung allograft dysfunction (CLAD).
      However, specific lung injury mechanisms are not clearly known. The objective of
      the study was to describe histopathological findings in surveillance lung
      transbronchial biopsies that can be correlated with episodes of BA in the lung
      allograft. METHODS: This retrospective analysis of surveillance transbronchial
      biopsies was performed in lung transplant recipients, with available data of
      broncho-alveolar fluid (cultures and cytology), lung function parameters, and
      esophageal functional tests. RESULTS: Were analyzed 11 patients, divided into 3
      groups: (1) GERD group: 4 patients with GERD and CLAD diagnosis; (2) control
      group: 2 patients without GERD or CLAD; and (3) BA group: 5 patients with foreign
      material in lung biopsies. A histopathological pattern of neutrophilic bronchitis
      (NB) was present in 4 of 4 cases in the GERD group and in 1 of 5 cases in the BA
      group in 2 or more biopsy samples; culture samples were all negative; the 5 NB
      positive patients developed CLAD and died (3/5) or needed re-transplantation
      (2/5). The other 3 patients in the BA group had GERD without NB or CLAD. Both
      patients in the control group had transient NB in biopsies with positive cultures
      but remained free of CLAD. CONCLUSIONS: Surveillance transbronchial biopsies may
      provide useful information other than the evaluation of acute cellular rejection
      and can help to identify high-risk patients for allograft dysfunction related to
      gastro-esophageal reflux.

PMID- 28457420
TI  - Atrophic Maxilla Reconstruction With Fresh Frozen Allograft Bone, Titanium Mesh,
      and Platelet-Rich Fibrin: Case Report.
AB  - The purpose of this article was to report the clinical and radiographic findings
      about a case of a man affected by severely atrophic maxilla to demonstrate the
      clinical proceedings associated with alveolar reconstruction destined for dental
      implant rehabilitation. The 3-dimensional augmentation of the alveolar ridge with
      the use of fresh-frozen bone graft, platelet-rich fibrin membrane, and titanium
      mesh suggests potential benefits to the development of the bone formation
      physiology. The treatment combination may result in an optimal prognosis and
      represents an option for reconstruction of bone defects. At 8 months after
      surgery, no evidence of complications was observed; the clinical examination and
      computerized tomographic scan revealed bone formation and installed implant
      stability.

PMID- 28457422
TI  - Co-transplantation of Xenogeneic Bone Marrow-derived Mesenchymal Stem Cells
      Alleviates Rejection of Pancreatic Islets in Non-obese Diabetic Mice.
AB  - Bone marrow-mesenchymal stem cells (BM-MSCs) have generated a great perspective
      in the field of regenerative medicine, and also in the treatment of inflammatory
      and autoimmune diseases in the past decade due to their immunomodulatory and anti
      inflammatory properties. Here, we investigated the effect of xenogeneic BM-MSCs
      and pancreatic islets co-transplantation obtained from Wistar rats in preventing
      rejection or inducing tolerance to islet transplantation in non-obese diabetic
      mice. Non-obese diabetic mice were treated with co-transplantation of pancreatic
      islets and BM-MSCs (islet + MSCs group) or pancreatic islets only (islet group).
      Compared to the islet group, islet + MSCs had a lower expression of inflammatory
      markers, such as, tumor necrosis factor- alpha (13.40 +/- 0.57 vs. 9.90 +/- 0.12,
      P = .01), monocyte chemoattractant protein 1 (51.30 +/- 6.80 vs. 9.00 +/- 1.80, P
      = .01), and interleukin 1beta (IL-1beta) (16.2 +/- 1.65 vs. 6.80 +/- 1.00, P =
      .04). Comparing the expression of immune tolerance markers, it is noted that
      animals receiving the co-transplantation showed a significantly higher expression
      than the islet group of IL-4 (25.60 +/- 1.96 vs. 2.80 +/- 0.20, P = .004), IL-10
      (188.40 +/- 4.60 vs. 4.55 +/- 0.12, P = .0001), and forkhead box P3 (34.20 +/-
      1.3 vs. 1.30 +/- 0.2, P = .004), respectively. These results suggest an
      immunomodulatory action of BM-MSC in islet xenotransplantation showing that these
      stem cells have the potential to mitigate the early losses of grafts, due to the
      regulation of the inflammatory process of transplantation.

PMID- 28457421
TI  - Later Evaluation of Ischemia and Reperfusion by the Pringle Maneuver in Wistar
      Rats, Demonstrating That Hepatic Lesions Can Be Reversible.
AB  - OBJECTIVE: There has been much research on hepatic ischemia and reperfusion by
      means of short or longer interruption of the portal triad. The aim of this work
      was to evaluate the mitochondrial respiratory activity and liver histology at 2
      different times after the Pringle maneuver. METHODS: Twenty-eight male Wistar
      rats, weighing ~308 g, with histologic and mitochondrial study: immediate
      ischemic group (IIG; 40 minutes; 9 animals) and late ischemic group (LIG; 28
      days; 9 animals). The rats were anesthetized and underwent a U-incision in the
      abdomen. In a simulated operation, manipulation of the hepatic pedicle was
      performed (5 animals immediate [ISG] and 5 late [LSG]). The hepatic pedicle was
      clamped for 20 minutes of ischemia foloowed by 20 minutes of reperfusion. The
      animals were killed under anesthesia. RESULTS: Mitochondria when stimulated by
      adenosine diphosphate or carbonylcyanide p-trifluoromethoxyphenylhydrazone had a
      significant respiratory reduction (P < .001). The respiratory control ratio in
      the LIG was altered (P < .02) compared with IIG. In the resting state, there was
      no change in the velocity of respiration between ischemic groups. Histopathologic
      findings showed 55.5% sinusoidal dilatation in IIG and 66.6% in LIG; 77.7%
      ballooning in IIG and 55.5% in LIG; and 11.1% focal necrosis in both IIG and LIG.
      CONCLUSIONS: The oxidative phosphorylation system recovered with improvement in
      mitochondrial respiration; however, morphologic recovery was associated with the
      type and intensity of injury.

PMID- 28457423
TI  - Mycotic Pseudoaneurysm After Kidney Transplantation: Two Case Reports.
AB  - BACKGROUND: Vascular complications after kidney transplantation may cause
      allograft loss. Here, we describe 2 patients with extrarenal mycotic
      pseudoaneurysm after kidney transplantation. PATIENTS: Patient 1 was a 54-year
      old man who developed pseudoaneurysm 60 days after transplantation, and patient 2
      was a 48-year-old woman who was diagnosed with a pseudoaneurysm 5 months after
      transplantation. RESULTS: Patient 1 had a deceased-donor kidney transplant with
      end-to-side external iliac arterial anastomosis that was reconstructed 8 days
      after transplantation owing to rupture and major bleeding. At 60 days after
      transplantation, he had high serum creatinine level and Doppler ultrasonography
      showed a pseudoaneurysm of the arterial graft anastomosis and postanastomotic
      renal artery stenosis. Treatment included surgical excision of the
      pseudoaneurysm, vascular reconstruction, and fluconazole, with mycologic culture
      of the resected pseudoaneurysm showing Candida albicans. Patient 2 developed
      nondisabling intermittent claudication at 5 months after kidney transplantation,
      with a pseudoaneurysm subsequently observed on Doppler ultrasonography and
      computerized tomographic angiography. Treatment included renal artery
      thrombectomy and common iliac bypass to the hilar donor renal artery with
      inverted ipsilateral long saphenous vein. Operative samples showed C albicans,
      and she was treated with fluconazole. Both patients had satisfactory outcomes,
      and both kidney allografts were preserved. CONCLUSIONS: Extrarenal mycotic
      pseudoaneurysms after kidney transplantation require a high index of suspicion
      for early diagnosis, and preservation of the kidney graft may be achieved with
      the use of surgical treatment and antifungal therapy.

PMID- 28457425
TI  - Erratum.

PMID- 28457424
TI  - What Can We Do When All Collapses? Fatal Outcome of Collapsing Glomerulopathy and
      Systemic Lupus Erythematosus With Diffuse Alveolar Hemorrhage: Case Report.
AB  - INTRODUCTION: Collapsing glomerulopathy (CG) is a rare form of glomerular injury.
      Although commonly associated with human immunodeficiency virus (HIV) infection,
      it can occur in association with systemic lupus erythematosus (SLE). CASE REPORT:
      We present the case of a 50-year-old man, with chronic kidney disease secondary
      to focal and segmental glomerulosclerosis, who received a cadaveric kidney
      transplant in 2007. There were no relevant intercurrences until May 2015, when he
      presented with nephrotic range proteinuria (+/- 4 g/d). A graft biopsy was
      performed and it did not show any significant pathological changes. In September,
      he developed a full nephrotic syndrome (proteinuria 19 g/d) and a graft biopsy
      was repeated. CG features were evident with a rich immunofluorescence.
      Antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies
      were positive; the remaining immunologic study was normal. Viral markers for HIV,
      hepatitis C virus (HCV), and hepatitis B virus (HBV) were negative. The patient
      was treated with corticosteroid pulses and plasmapheresis (seven treatments). A
      rapid deterioration of kidney function was seen and he became dialysis dependent.
      He was discharged with a low-dose immunosuppressive treatment. In October, he was
      hospitalized with diffuse alveolar hemorrhage (DAH). The auto-immune study was
      repeated, revealing complement consumption and positive titers of ANA and Anti
      dsDNA antibodies. Anti-neutrophil cytoplasmic antibodies (ANCAs) and
      antiglomerular basement membrane antibody (anti-GBM) were negative. Treatment
      with intravenous corticosteroids, plasmapheresis, and human immunoglobulin was
      ineffective and the outcome was fatal. CONCLUSION: This case report highlights
      the possible association of CG and SLE. To our knowledge, it is the first case of
      SLE presenting with CG and DAH, with the singularity of occurring in a kidney
      transplant recipient receiving immunosuppression.

PMID- 28457426
TI  - Erratum.

PMID- 28457427
TI  - Blood flow velocity prediction in aorto-iliac stent grafts using computational
      fluid dynamics and Taguchi method.
AB  - Covered Endovascular Reconstruction of Aortic Bifurcation (CERAB) is a new
      technique to treat extensive aortoiliac occlusive disease with covered expandable
      stent grafts to rebuild the aortoiliac bifurcation. Post stenting Doppler
      ultrasound (DUS) measurement of maximum peak systolic velocity (PSVmax) in the
      stented segment is widely used to determine patency and for follow up
      surveillance due to the portability, affordability and ease of use. Anecdotally,
      changes in hemodynamics created by CERAB can lead to falsely high PSVmax
      requiring CT angiography (CTA) for further assessment. Therefore, the importance
      of DUS would be enhanced with a proposed PSVmax prediction tool to ascertain
      whether PSVmax falls within the acceptable range of prediction. We have developed
      a prediction tool based on idealized models of aortoiliac bifurcations with
      various infra-renal PSV (PSVin), iliac to aortic area ratios (R) and aortoiliac
      bifurcation angles (alpha). Taguchi method with orthogonal arrays (OA) was
      utilized to minimize the number of Computational Fluid Dynamics (CFD) simulations
      performed under physiologically realistic conditions. Analysis of Variance
      (ANOVA) and Multiple Linear Regression (MLR) analyses were performed to assess
      Goodness of fit and to predict PSVmax. PSVin and R were found to contribute
      94.06% and 3.36% respectively to PSVmax. The Goodness of fit based on adjusted R2
      improved from 99.1% to 99.9% based on linear and exponential functions. The
      PSVmax predictor based on the exponential model was evaluated with sixteen
      patient specific cases with a mean prediction error of 9.9% and standard
      deviation of 6.4%. Eleven out of sixteen cases (69%) in our current retrospective
      studies would have avoided CTA if the proposed predictor was used to screen out
      DUS measured PSVmax with prediction error greater than 15%. The predictor
      therefore has the potential to be used as a clinical tool to detect PSVmax more
      accurately post aortoiliac stenting and might reduce diagnostic errors and avoid
      unnecessary expense and risk from CTA follow-up imaging.

PMID- 28457428
TI  - Superabsorbent hydrogel made of NaAlg-g-poly(AA-co-AAm) and rice husk ash:
      Synthesis, characterization, and swelling kinetic studies.
AB  - The sodium alginate-g-poly(acrylic acid-co-acrylamide)/rice husk ash (NaAlg-g
      P(AA-co-AAm)/RHA) superabsorbent nanocomposite was synthesized by the free
      radical graft copolymerization of alginate (NaAlg), acrylic acid (AA), acrylamide
      (AAm), and RHA in aqueous solution. FTIR spectra revealed that the monomers were
      grafted onto NaAlg chains, and the nanocomposite was formed successfully.
      Incorporation of RHA into hydrogel matrix formed porous interlinked channels
      within hydrogel network. Superabsorbent nanocomposite showed greater equilibrium
      swelling capacity (1070g/g) compared with neat hydrogel (830g/g). Moreover, water
      transport mechanism of all hydrogels was non-Fickian diffusion type. Rheological
      measurements confirmed effective role of RHA in improving gel strength of
      superabsorbent nanocomposite. The influence of various factors, such as different
      loads (0.3, 0.6, 0.9 psi), solution pH, saline solution, and temperature on the
      swelling behavior of hydrogels was also assessed. Superabsorbent nanocomposite
      exhibited good pH-dependent swelling reversibility and high water retention
      capability, making it more efficient water-saving material for agricultural and
      horticultural applications.

PMID- 28457429
TI  - Modified-epsilon-polylysine-grafted-PEI-beta-cyclodextrin supramolecular carrier
      for gene delivery.
AB  - Cyclodextrin-based supermolecular systems have become one of significant nonviral
      gene delivery carriers. In this study, epsilon-polylysine-grafted-succinic acid
      grafted-beta-cyclodextrin-LMW PEI (PPC) and adamantane-functionalized poly
      (ethylene glycol) derivative (PEG-AD) were synthesized, and PEG-AD was
      encapsulated into PPC to form the complexes. These complexes were used to
      condense pDNA to make polyplexes, which biophysical properties, cytotoxicity and
      transfection efficiencies were studied. The results showed that the polyplexes
      were less cytotoxic than branched PEI without degrading the transfection
      efficiency. These findings suggest that the complexes with high stability could
      be an effective and low-toxicity carrier for delivering nucleic acid to target
      cells.

PMID- 28457430
TI  - Synthesis of cellulose-based double-network hydrogels demonstrating high
      strength, self-healing, and antibacterial properties.
AB  - Novel antibacterial double-network (DN) hydrogels with superior mechanical and
      self-healing properties are developed via the UV-initiated copolymerization of
      polyacrylic acid (PAA)-grafted quaternized cellulose (QCE) and polyvinyl alcohol
      (PVA). The QCE functioned as an antibacterial agent, resulting in excellent
      antibacterial capability (antibacterial rate >93%). The hydrogels are thus
      protected from microbial attack in natural environments, prolonging their
      lifetime. The PVA functioned as a physical cross-linker, resulting in superior
      mechanical properties. At PVA and QCE contents of 8% and 1.5%, respectively, the
      strain and stress at break of hydrogel were 465.37% and 1.13MPa, respectively.
      The hydrogel maintained good self-healing properties owing to ionic bonding
      between the ferric ions and carboxylic groups, and hydrogen bonding between the
      PVA molecules. The hydrogel was responsive to pH; its water-holding ability could
      be controlled by changing the pH. The material is simply prepared and used.
      Hydrogels with such excellent properties could be applied in various biomedical
      fields.

PMID- 28457431
TI  - Understanding the role of water in the interaction of ionic liquids with wood
      polymers.
AB  - Hemicellulose lean pulps are a raw material source for numerous high value
      products. We have previously presented the IONCELL-P(ulp) process, a
      hemicellulose extraction method, based on a binary mixture of ionic liquid and
      water. The IONCELL-P process does not suffer from yield losses or polymer
      degradation and retains the Cellulose I crystalline form. In this paper, a
      selection of cellulose dissolving ionic liquids is tested, in order to compare
      their applicability in the process. We demonstrate that the extraction
      selectivity towards low molar mass polymers is related to the anion's ability to
      accept hydrogen bonds (Kamlet-Taft beta-value), if divided by the water molar
      fraction of the solvent system. Pulp consistency, solvent system viscosity and pH
      are investigated in order to identify the factors affecting the extraction
      efficiency. The results show that all the tested ionic liquid-water mixtures were
      able to dissolve hemicelluloses, but there were differences in their efficiency,
      selectivity and the ability to process high pulp consistencies.

PMID- 28457432
TI  - beta-Cyclodextrin capped graphene-magnetite nanocomposite for selective
      adsorption of Bisphenol-A.
AB  - Beta-cyclodextrin capped Graphene-magnetite (G-Fe3O4-BCD) nanocomposite was
      synthesized by ethylenediamine conjugation and used as an adsorbent for selective
      removal of Bisphenol-A (BPA) in water. Characterization of nanocomposite revealed
      BCD conjugated to Fe3O4 nanoparticles (30-40nm) embedded on graphene. Adsorption
      process followed Langmuir model and pseudo second order kinetics with an
      adsorption capacity of 59.6mg/g. It was found to be highly favourable
      physisorption and endothermic process as indicated by DeltaG degrees  (
      3.36kJ/mol) and DeltaH degrees  (2.08kJ/mol) values at ambient temperatures. The
      nanocomposite was highly specific towards BPA compared to its analogs, largely
      driven by host-guest interaction between BCD and BPA. Nanocomposite had a high
      magnetization of 97emu/g with superparamagnetic property at room temperature
      which helps in faster separation using an external magnetic field. Nanocomposite
      can be regenerated with methanol and can be reused without much loss in
      adsorption efficiency (<10%) after 6 cycles. It has huge potential and
      application in selective adsorption of target molecules.

PMID- 28457433
TI  - Purification of glucomannan from salep: Part 1. Detailed rheological
      characteristics.
AB  - The aim of this study was to investigate the effects of different extraction
      temperatures (25, 55 and 85 degrees C) on the rheological characteristics of
      glucomannan (GM) purified from salep. GM was isolated using the following method:
      extraction of GM with water, removal of impurities by centrifugation and
      precipitation of GM with ethanol. The extraction yield of GM was approximately
      45% for all products. Higher GM (95%) and lower starch (3%) contents were
      obtained for GM25. GM25 showed higher apparent and intrinsic viscosity, storage
      and loss modulus and lower activation energy than GM55 and GM85. The addition of
      different salts and sugars did not affect viscosity due to the non
      polyelectrolyte behavior of GM. Gel behavior of purified samples appeared at pH
      9. The usage of salep in milk was reduced by purification. These results are
      potentially useful for widening the applications for salep and for furthering
      research and development of GM.

PMID- 28457434
TI  - Fabrication and study of curcumin loaded nanoparticles based on folate-chitosan
      for breast cancer therapy application.
AB  - Purpose of this article is developing novel, inexpensive curcumin loaded chitosan
      nanoparticles with targeting ability. Curcumin loaded folate-modified-chitosan
      nanoparticles (NPs) have been synthesized and fabricated via self-assembling
      process. Chemical structures of modified chains, nanoparticle size in dry and wet
      state, zeta potential, morphology of NPs, physical state of curcumin in NPs, drug
      release profile and cytotoxicity of NPs were investigated by FTIR, FE-SEM, DLS
      and XRD, UV-vis spectrophotometer, and MTT assay against L929 and MCF7 cell
      lines, respectively. Results show nanoparticle size in dry state varied in range
      of 119-127nm and curcumin was loaded into nanoparticles with 96.47% efficacy.
      Drug release studies showed by decreasing pH of release medium from 7.4 to 5,
      release rate of curcumin from NPs increased, which shows pH responsive capacity
      of folate-modified chitosan nanoparticles. Cell viability studies confirmed that
      curcumin loaded NPs have good potential as a drug delivery system for breast
      cancer therapy.

PMID- 28457435
TI  - High strength, biocompatible hydrogels with designable shapes and special hollow
      formed character using chitosan and gelatin.
AB  - Hydrogels with good mechanical properties, excellent biocompatibility and
      designable shapes are of great importance for their biomedical applications.
      Herein, a series of high strength, biocompatible hydrogels have been synthesized
      by integrating sodium citrate into the thermally reversible chitosan/gelatin to
      form multiple physically crosslinking networks. Besides the ideal formability, a
      thermal etching or welding method has been developed to program the surface
      morphology and fabricate hydrogels with complicated shapes freely. More
      impressively, the special hollow "cup-shaped and tubular" structure has also been
      constructed by applying an interrupted gelation process in controlled ion
      crosslinking time and the subsequent dissolving process at 37 degrees C in
      deionized water. The high strength, biocompatible hydrogels with special internal
      and external shape adjustable characters, potentially useful in vascular repair
      and substitutes of cartilage, may further broaden our understanding of the
      plasticity of the hydrogels.

PMID- 28457436
TI  - Electrospun H4SiW12O40/cellulose acetate composite nanofibrous membrane for
      photocatalytic degradation of tetracycline and methyl orange with different
      mechanism.
AB  - H4SiW12O40 (SiW12)/cellulose acetate (CA) composite nanofibrous membrane was
      prepared by electrospinning in which CA was employed as the support of SiW12.
      Characterization with Fourier transformation infrared spectroscopy (FT-IR),
      Energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy
      (XPS) indicated that SiW12 has been successfully loaded into the CA membrane and
      its Keggin structure remained intact. The as-prepared composite membrane
      exhibited enhanced photocatalytic activity in the decomposition of tetracycline
      (TC) and methyl orange (MO) compared with pure SiW12 under ultraviolet
      irradiation. The optimal mass ratio of SiW12 to CA was 1:4, and the corresponding
      degradation efficiency for TC and MO was 63.8% and 94.6%, respectively. It is
      noteworthy that the degradation rate of MO increased more evidently than that of
      TC under the same conditions, which may be attributed to the different role that
      CA nanofibrous membrane played in the TC and MO photodegradation process. Besides
      providing more contact area between SiW12 and the pollutant in TC
      photodegradation, CA membrane played an additional role that donated electron to
      SiW12 in the MO degradation process, leading to a different photocatalytic
      mechanism with greatly enhanced degradation rate. Moreover, the composite
      membrane presented an excellent reusability, which was mainly ascribed to the
      water-insolubility of CA and the hydrogen bonds between CA and SiW12. This work
      will be useful for the design of biopolymer-based membrane photocatalysts applied
      to antibiotics and dyes wastewater treatment.

PMID- 28457438
TI  - Characterization of methacrylated polysaccharides in combination with amine-based
      monomers for application in mortar.
AB  - Smart pH-responsive superabsorbent polymers (SAPs) could be useful for self
      healing of cracks in mortar. They will swell minimally during the alkaline
      conditions of mixing, leading to only small macro-pores but will swell stronger
      with a lower pH when water enters the cracks. As such, polysaccharides (alginate,
      chitosan and agarose) were methacrylated and cross-linked with amine-based
      monomers (dimethylaminoethyl methacrylate and dimethylaminopropyl methacrylamide)
      to induce a varying pH-sensitivity. These materials showed a strong cross-linking
      efficiency and induced moisture uptake capacities up to 122% at 95% relative
      humidity with a negligible hysteresis. Additionally, interesting pH-responsive
      swelling capacities were obtained, especially for SAPs based on chitosan and
      agarose with values up to 110gwater/gSAP. Most of these materials showed limited
      hydrolysis in cement filtrate solutions, making them very promising for use in
      mortar.

PMID- 28457437
TI  - Nanostructured cellulose-xyloglucan blends via ionic liquid/water processing.
AB  - In this work, the properties of cellulose (CE)/xyloglucan (XG) biopolymer blends
      are investigated, taking inspiration from the outstanding mechanical properties
      of plant cell walls. CE and XG were first co-solubilized in an ionic liquid, 1
      ethyl-3-methylimidazolium acetate, in order to blend these biopolymers with a
      varying CE:XG ratio. The biopolymers were then regenerated together using water
      to produce solid blends in the form of films. Water-soluble XG persisted in the
      films following regeneration in water, indicating an attractive interaction
      between the CE and XG. The final CE:XG ratio of the blends was close to the
      initial value in solutions, further suggesting that intimate mixing takes place
      between CE and XG. The resulting CE/XG films were found to be free of ionic
      liquid, transparent and with no evidence of phase separation at the micron scale.
      The mechanical properties of the blend with a CE:XG ratio close to one revealed a
      synergistic effect for which a maximum in the elongation and stress at break was
      observed in combination with a high elastic modulus. Atomic force microscopy
      indicates a co-continuous nanostructure for this composition. It is proposed that
      the non-monotonous variation of the mechanical performance of the films with XG
      content is due to this observed nanostructuration.

PMID- 28457439
TI  - Conducting cellulose/TiO2 composites by in situ polymerization of pyrrole.
AB  - Cellulose/polypyrrole and cellulose/polypyrrole-TiO2 composites were prepared via
      in situ oxidative chemical polymerization of pyrrole using FeCl3 as oxidant. The
      concentration effect of pyrrole on the structure and properties of prepared
      matrix has been investigated. Furthermore, the structure of the prepared
      materials was characterized using Fourier transform infrared spectroscopy (FTIR),
      Scanning electron microscopy (SEM), X-ray Diffraction (XRD), and Thermal
      gravimetrical analysis (TGA). The results exhibited that the addition of
      cellulose and TiO2 increase the thermal stability of the polypyrrole system.
      Moreover, dielectric properties of the obtained composites were studied over
      frequency range from 42Hz to 5MHz. The electrical measurements including
      dielectric constant, epsilon'(omega), dielectric loss, epsilon''(omega), loss
      tangent, tan delta and ac conductivity, sigmaac were carried.

PMID- 28457440
TI  - Enhanced Antibacterial effect using carbohydrates biotemplate of ZnO nano thin
      films.
AB  - Carbohydrate biotemplates of glucose (C6H12O6) and starch (C6H12O6)n in to Zinc
      oxide (ZnO) nano thin films (NTFs) prepared for enhanced antibacterial activity
      by Successive Ionic Layer Adsorption Reaction (SILAR). X-ray diffraction (XRD)
      patterns revealed that the crystalline size values were decreased by the
      incorporation of carbohydrate molecules. Scanning electron microscope (SEM) and
      Field emission scanning electron microscope (FESEM) confirmed that the different
      morphologies by the addition of glucose and starch. The interactions of
      carbohydrate molecules with ZnO were identified by using FTIR and EDAX. Energy
      band gap of samples was calculated by UV absorption spectra. The emission
      property of Zinc oxide, Glucose/ZnO and Starch/ZnO was studied by
      photoluminescence (PL) spectra. The antibacterial activity of carbohydrate
      biotemplates (Cbts-ZnO) results showed that enhanced effect than pure ZnO for the
      selected pathogenic bacteria's.

PMID- 28457441
TI  - Improved flame-retardant and tensile properties of thermoplastic starch/flax
      fabric green composites.
AB  - This article highlights the development of biodegradable flame-retardant
      composites using a compression technique on low-cost starch, flax fabric (FF) and
      ammonium polyphosphate (APP) raw materials. The starch was plasticized into
      thermoplastic starch through a mechano-ball milling process and composites were
      developed by reinforcing the FF and incorporating varying amounts of APP. The
      effects of APP on the flammability and thermal properties of the composites were
      studied. Limited oxygen index and horizontal-burning tests exhibited significant
      sustainability of the composites toward flame and direct flame self
      extinguishment. It was observed that at higher temperatures, APP leads to
      formation of thermally stable char. The flame retardant properties of the
      composites were speculated to be due to the protective compact crosslinked
      network (POP and POC) of the char. The reported effects of APP include
      improvement in mechanical and biodegradation properties. This investigation
      provides the design of novel flame-retardant green composites with excellent
      properties.

PMID- 28457442
TI  - Synthesis of hybrid paper sheets with enhanced air barrier and antimicrobial
      properties for food packaging.
AB  - Paper sheets made from bagasse pulp have been modified using nanocellulose (NC)
      obtained from the same raw material. Modification of paper sheets have been
      carried out either through loading of paper with different concentrations of NC
      and antibacterial agent, Chitosan (Ch) during making sheets, or by surface
      coating of the paper. Crystals of NC extracted using concentrated sulfuric acid
      from bagasse pulp were found to have crystallinity index (CrI) 90%. Morphology of
      obtained NC has been confirmed by TEM and images revealed formation of NC
      crystals with large size distribution ranges from 4 to 60nm. Mechanical
      properties and air permeability of paper sheets loaded with different ratios of
      NC and Ch have been investigated. The results showed that presence of NC did not
      negatively affect the obtained modified paper sheets, while air permeability
      decreased with adding 8% NC to paper matrix. On the other hand, surface coverage
      of paper sheets with NC greatly reduced air permeability. Antimicrobial
      investigations carried out by optical density method indicated that presence of
      Ch in the paper sheets as an additive or in a coating formulation enhanced paper
      resistance to different microorganisms especially those causing food poisoning.
      The current study confirms that the modified paper can have potential application
      in food packaging.

PMID- 28457443
TI  - Dextran production by Lactobacillus sakei MN1 coincides with reduced
      autoagglutination, biofilm formation and epithelial cell adhesion.
AB  - In this work we have investigated two dextran-producing lactic acid bacteria,
      Lactobacillus sakei MN1 and Leuconostoc mesenteroides RTF10, isolated from
      fermented meat products. These bacteria synthesise dextran when sucrose, but not
      glucose, is present in the growth medium. The influence of dextran on bacterial
      aggregation, adhesion and biofilm formation was investigated in cultures
      challenged with sucrose or glucose. For Lb. sakei MN1, the synthesis of the
      dextran drastically impaired the three processes; in contrast it had no effect on
      Lc. mesenteroides RTF10. Therefore, the influence of dextran on probiotic
      properties of Lb. sakei MN1 was tested in vivo using gnotobiotic zebrafish
      models. The bacterium efficiently colonised the fish gut and inhibited the
      killing activity of Vibrio anguillarum NB10[pOT11]. Furthermore, under conditions
      of dextran synthesis, the adhesion of Lb. sakei MN1 to the epithelial cells
      decreased, without greatly affecting its anti V. anguillarum activity.

PMID- 28457444
TI  - Photocrosslinked maleilated chitosan/methacrylated poly (vinyl alcohol)
      bicomponent nanofibrous scaffolds for use as potential wound dressings.
AB  - To improve water stability of hydrophilic nanofibers, photocrosslinked maleilated
      chitosan/methacrylated poly (vinyl alcohol) (MCS/MPVA) bicomponent nanofibrous
      scaffolds were successfully obtained by electrospinning of aqueous MCS/MPVA
      solution and consequent photopolymerization. The parameters of MCS/MPVA solutions
      such as viscosity and conductivity were measured to evaluate electrospinnability
      of the blend solutions. The bicomponent nanofibrous scaffolds were characterized
      by scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis and
      differential scanning calorimetry (DSC), respectively. SEM results indicated that
      MCS/MPVA weight ratios significantly influenced the morphology and diameter
      distribution of the nanofibers. XRD and DSC investigated that there was strong
      interaction caused by hydrogen bonding between molecular chain of MCS and MPVA.
      Water stability test confirmed that the photocrosslinked matrix with a MCS/MPVA
      ratio of 10/90 retained excellent integrity of the fibrous structure in water.
      The in vitro cytotoxicity evaluation revealed that photocrosslinked nanofibrous
      scaffolds entailed good cellular compatibility, and could be used as potential
      wound dressing.

PMID- 28457445
TI  - Emerging concepts in the nutraceutical and functional properties of pectin-A
      Review.
AB  - Pectin is a structural heteropolysaccharide found ubiquitously in terrestrial
      plants. It finds diverse food applications such as that of a gelling agent,
      stabilizer, and fat replacer. In the pharmaceutical arena, pectin exhibits a
      number of functions, from decreasing blood fat to combating various types of
      cancers. This review shows the shift of pectin from its conventional roles to its
      progressive applications. Insights into the advances in the production of pectin,
      the role it plays as a nutraceutical, possible prebiotic potential and a delivery
      vehicle for probiotics, and food applications are highlighted. Bioactive and
      functional properties of pectin are discussed and how the structural built up
      defines them, is emphasized. As a biopolymer, the applications of pectin in
      active packaging are also mentioned.

PMID- 28457447
TI  - Preparation and characterization of cellulose laurate ester by catalyzed
      transesterification.
AB  - The preparation of cellulose laurate was investigated through transesterification
      in 1-allyl-3-methylimidazolium chloride (AmimCl)/dimethyl sulfoxide (DMSO)
      cosolvent system by using vinyl laurate as an acylation reagent and 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) as an effective catalyst. The effects of
      reaction temperature, reaction time and the molar ratio of vinyl laurate to
      anhydride glucose unit (AGU) were investigated. The degree of substitution (DS)
      ranged from 1.47 to 2.74 under the selected conditions and the reaction order of
      three hydroxyl groups was C-6>C-3>C-2. The chemical structure cellulose laurate
      were explored by Fourier transform infrared (FT-IR) spectroscopy, 1H-nuclear
      magnetic resonance (NMR), 13C NMR, heteronuclear single quantum correlation
      (HSQC) and X-ray diffraction (XRD) to confirm the occurrence of
      transesterification. The improved thermal stability of cellulose laurate was
      proved by the thermogravimetric analysis (TGA). The tensile analysis and the
      contact angle measurement confirmed the ductile behavior and the hydrophobicity
      of the films made from cellulose laurate.

PMID- 28457446
TI  - Cellulose derivative-lanthanide complex film by hierarchical assembly process.
AB  - Carboxymethylcellulose (CMC), quaternized cellulose (QC) and lanthanide (Ln) ion
      ternary complex thin film was fabricated by hierarchical assembly process. CMC is
      a weak anionic polyelectrolyte while QC is a cationic polyelectrolyte. Strictly
      controlling pH value and molar ratio, CMC and Ln ion were prepared into polymer
      metal complex nano-particles (CMC@Ln) which exhibit negative charge on surface,
      and then the nano-particles were layer-by-layer (LbL) assembled with positively
      charged QC to prepare thin films. Three kinds of Ln ion, Ce3+, Eu3+, and Tb3+
      were successfully incorporated into films separately, and the corresponding films
      showed blue, green and red fluorescence color. In addition, we can adjust the
      luminescence of the film with combination of CMC@Ce, CMC@Eu, and CMC@Tb complex
      nano-particles.

PMID- 28457448
TI  - Crystallization and mechanical properties of reinforced PHBV composites using
      melt compounding: Effect of CNCs and CNFs.
AB  - Nanocellulose reinforced poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)
      composites were prepared using melt compounding. The effects of nanocellulose
      types (CNCs and CNFs) and nanocellulose content (1, 2, 3, 4, 5, 6 and 7wt%) on
      the crystallization, thermal and mechanical properties of PHBV composites were
      systematically compared in this study. The thermal stability of PHBV composites
      was improved by both CNCs and CNFs. CNFs with a higher thermal stability leaded
      to a higher thermal stability of PHBV composites. Both CNCs and CNFs induced a
      reduction in the crystalline size of PHBV spherulites. Furthermore, CNCs could
      act as a better nucleating agent for PHBV than did CNFs. CNCs and CNFs showed
      reinforcing effects in PHBV composites. At the equivalent content of
      nanocellulose, CNCs led to a higher tensile modulus of PHBV composites than did
      CNFs. 1wt% CNCs/PHBV composites exhibited the most optimum mechanical properties.

PMID- 28457450
TI  - Borax cross-linked guar gum hydrogels as potential adsorbents for water
      purification.
AB  - With the aim to explore new adsorbents for water purification, guar gum based
      hydrogels were synthesized by cross-linking with borax at different percentage.
      The cross-linking was confirmed through characterization by FTIR spectroscopy,
      SEM morphology, thermal studies and water absorption capacity. To examine the
      adsorption/absorption performance of different grades of hydrogels, their
      flocculation efficiency was studied in kaolin suspension at different pH by
      standard jar test procedure. The flocculation efficiency of the test materials
      was compared with the commercially used coagulant, alum and also residues of Al
      and K left in the treated water were comparatively studied. The synthesized
      hydrogels were also tested for their efficiency of removing Aniline Blue dye by
      UV-vis spectrophotometer study. The best grade hydrogel outperformed alum, at
      extremely low concentration and also showed dye removing efficiency up to 94%.
      The single step synthesized green products thus exhibited great potential as
      water purifying agents.

PMID- 28457449
TI  - Stress sensitive electricity based on Ag/cellulose nanofiber aerogel for self
      reporting.
AB  - A self-reporting aerogel toward stress sensitive slectricity (SSE) was presented
      using an interconnected 3D fibrous network of Ag nanoparticles/cellulose
      nanofiber aerogel (Ag/CNF), which was prepared via combined routes of silver
      mirror reaction and ultrasonication. Sphere-like Ag nanoparticles (AgNPs) with
      mean diameter of 74nm were tightly anchored in the cellulose nanofiber through by
      the coherent interfaces as the conductive materials. The as-prepared Ag/CNF as a
      self-reporting material for SSE not only possessed quick response and
      sensitivity, but also be easily recovered after 100th compressive cycles without
      plastic deformation or degradation in compressive strength. Consequently, Ag/CNF
      could play a viable role in self-reporting materials as a quick electric-stress
      responsive sensor.

PMID- 28457451
TI  - Folic acid functionalized reduction-responsive magnetic chitosan nanocapsules for
      targeted delivery and triggered release of drugs.
AB  - A versatile folic acid (FA)-functionalized reduction-responsive magnetic chitosan
      (CS) nanocapsules (FA-RMCNCs) were designed and fabricated successfully from FA
      functionalized thiolated chitosan with a simple sonochemical method. The
      targeting molecule (FA), red fluorescent probes (Rhodamine B isothiocyanate,
      RITC) and thiolated Fe3O4 magnetic nanoparticles (Fe3O4-SH MNPs) were immobilized
      in and onto the shells of nanocapsules. The as-synthesized FA-RMCNCs had a well
      defined spherical morphology with the size of 200-350nm. As the carriers, FA
      RMCNCs showed an excellent magnetic responsive property. The CLSM analysis
      revealed that the proposed FA-RMCNCs with core-shell constructure could be
      internalized selectively by the HeLa cells through the folate-mediated
      endocytosis. Moreover, the reductant-triggered release of coumarin 6 suggested
      that the FA-RMCNCs possessed superior reduction-responsivity of drug release.
      This study reveals the potential of FA-RMCNCs as magnetic/reduction dual
      responsive, folate-receptor-mediated targeting nanocarriers in targeted delivery
      and controlled release of hydrophobic drugs.

PMID- 28457452
TI  - Rheology of Laponite-scleroglucan hydrogels.
AB  - Both Laponite and scleroglucan can find several applications in various fields
      (from industrial to biomedical one) in virtue of their peculiar features and
      rheological properties displayed in aqueous phases. Structural states of Laponite
      dispersions strongly depend on concentration and ionic strength. When attractive
      and repulsive interparticle interactions are so effective that they lead to
      arrested states (attractive gel or repulsive glass), the rheological behavior of
      the dispersion undergoes a sharp transition, from quasi-Newtonian to markedly
      shear thinning and viscoelastic. Conversely, scleroglucan solutions gradually
      change to weak gels with increasing polymer concentration. The present work is
      concerned with aqueous Laponite-scleroglucan mixed systems, obtained according to
      different preparation modes, and is aimed at examining how much the content and
      proportion of both components affect the viscoelastic and flow properties of the
      mixed system.

PMID- 28457453
TI  - Structural dependence on the property of chiral stationary phases derived from
      chitosan bis(arylcarbamate)-(amide)s.
AB  - The goal of present study was to investigate the structural dependence of
      chitosan derivatives on enantioseparation and mobile phase tolerance of the
      corresponding chiral packing materials for liquid chromatography. Hence, a series
      of chitosan bis(arylcarbamate)-(n-pentyl amide)s and the related chiral
      stationary phases (CSPs) were prepared from chitosans with different molecular
      weights. Because of the H-bond formed via CH3-pi interaction, the CSP bearing
      methyl substituent exhibited high tolerance than the ones bearing dichloro
      substituents. The CSP derived from the chitosan bis(3,5-dichlorophenylcarbamate)
      (n-pentyl amide) with a higher molecular weight possessed high tolerance to
      mobile phases, whereas the enantioseparation capability of this CSP was not as
      good as that of the one prepared from the chitosan derivative with a lower
      molecular weight. Therefore, enantioseparation capability and mobile phase
      tolerance have to be counterbalanced in designing chiral selectors for the CSPs
      derived from chitosan bis(arylcarbamate)-(amide)s.

PMID- 28457454
TI  - Mussel-inspired chitosan-polyurethane coatings for improving the antifouling and
      antibacterial properties of polyethersulfone membranes.
AB  - A straightforward mussel-inspired approach was proposed to construct chitosan
      polyurethane coatings and load Ag nanoparticles (AgNPs) to endow polyethersulfone
      (PES) membranes with dual-antibacterial and antifouling properties. The
      macromolecule O-carboxymethyl chitosan (CMC) was directly reacted with catechol
      in the absence of carbodiimide chemistry to form the coating and load AgNPs via
      in situ reduction; while lysine (Lys) was used as a representative small molecule
      for comparison. Then, PEG-based polyurethane (PU) was used for constructing Lys
      Ag-PU and CMC-Ag-PU composite coatings, which substantially improved the protein
      antifouling property of the membranes. Furthermore, the CMC-Ag-PU coating
      exhibited superior broad-spectrum antibacterial property towards E. coli and S.
      aureus than Lys-Ag-PU coating. Meanwhile, the CMC-Ag-PU coating showed sustained
      antifouling property against bacteria and could reload AgNPs to be regenerated as
      antibacterial and antifouling coating. This approach is believed to have
      potential to fabricate reusable antifouling and antibacterial coatings on
      materials surfaces for aquatic industries.

PMID- 28457455
TI  - Alginate microparticles as oral colon drug delivery device: A review.
AB  - The increase in the research interest on alginate microparticles in
      pharmaceutical and biomedical areas confirms its potential use as an effective
      matrix for drug and cell delivery. Among the well known alginate properties, pH
      sensitivity remains as an attractive option for targeting of drug in the colon
      region. This essential aspect is advantageous to enhance therapeutic efficacy of
      treatment of inflammatory bowel diseases, which require multi-drug administration
      frequently in a long period. As consequence, severe side effect appears leading
      to discontinuation of therapy and affecting quality of patient life. This review
      gives an overview of relevant properties of alginate as oral colon delivery
      systems and the recent innovative strategies of using alginate with other
      polymers as well as microencapsulation techniques. At the same time, it describes
      the several advantages of coating processes involving alginate over
      microparticles in order to design better material with sustained release
      characteristic for colon-targeted delivery.

PMID- 28457456
TI  - Carboxymethyl cellulose/graphene oxide bio-nanocomposite hydrogel beads as
      anticancer drug carrier agent.
AB  - Biodegradable carboxymethyl cellulose/graphene oxide (CMC/GO) nanocomposite
      hydrogel beads as a drug delivery system were prepared via physically
      crosslinking with FeCl3.6H2O for controlled release of anticancer drug
      doxorubicin (DOX). The pi-pi stacking interaction between DOX and GO resulted in
      higher loading capacity and controlled release of the DOX loaded from CMC/GO
      nanocomposites hydrogel. The release profile of DOX from hydrogel beads at pH 6.8
      and 7.4 indicated it's strongly pH dependence. Interaction between GO and DOX
      with H-bonding could be unstable under acidic conditions which resulted in faster
      drug release rate in pH 6.8. The formation of GO nanoparticles in the hydrogels
      was confirmed using X-ray diffraction (XRD), and the chemical structure and
      morphology of the prepared CMC/GO nanocomposite hydrogel beads were characterized
      using Fourier transform infrared spectroscopy (FT-IR), SEM and Transmission
      electron microscopy (TEM). In addition, swelling behavior of nanocomposite
      hydrogels was investigated in PBS solution.

PMID- 28457457
TI  - Effect of different drying procedures on the bioactive polysaccharide acemannan
      from Aloe vera (Aloe barbadensis Miller).
AB  - The main effects of different drying procedures: spray-, industrial freeze-,
      refractance window- and radiant zone-drying, on acemannan, the main bioactive
      polysaccharide from Aloe vera gel, were investigated. All the drying procedures
      caused a considerable decrease in the acemannan yield (~40%). Degradation
      affected not only the backbone, as indicated by the important losses of (1->4)
      linked mannose units, but also the side-chains formed by galactose. In addition,
      methylation analysis suggested the deacetylation of mannose units (>60%), which
      was confirmed by 1H NMR analysis. Interestingly, all these changes were reflected
      in the functional properties which were severely affected. Thus, water retention
      capacity values from processed samples decreased ~50%, and a reduction greater
      than 80% was determined in swelling and fat adsorption capacity values.
      Therefore, these important modifications should be taken into consideration,
      since not only the functionality but also the physiological effects attributed to
      many Aloe vera-based products could also be affected.

PMID- 28457458
TI  - Carbohydrate biopolymer for corrosion control of 6061 Al-alloy and 6061Aluminum
      15%(v) SiC(P) composite-Green approach.
AB  - The acid corrosion control of 6061Aluminum alloy and 6061Al-15%(v) SiC(P)
      composite material (Al-CM) was carried by using inulin - a carbohydrate polymer
      as a green inhibitor. Potentiodynamic polarization (PDP) and Electrochemical
      Impedance Spectroscopy (EIS) techniques were adopted. Concentration of inulin was
      in the range of 0.2gL-1-1.0gL-1, and studies were done in the temperature range
      of 303-323K. The adsorption of inhibitor on the surface of Al alloy and Al-CM was
      confirmed by physical techniques such as Scanning electron microscopy (SEM),
      energy-dispersive X-Ray analysis (EDX), and atomic force microscopy (AFM)
      analysis. The studies showed that inhibition efficiency of inhibitor increased
      with increase in concentrations of inulin and decreased with increase in
      temperature. The adsorption of inulin on metal surface obeyed Langmuir adsorption
      isotherm through physical adsorption on both alloy and on Al-CM. Results obtained
      from potentiodynamic polarization method and electrochemical impedance
      spectroscopic methods were in good agreement with one another.

PMID- 28457459
TI  - Optical sensor platform based on cellulose nanocrystals (CNC) - 4'-(hexyloxy)-4
      biphenylcarbonitrile (HOBC) bi-phase nematic liquid crystal composite films.
AB  - The preparation of composite materials has gained tremendous attention due to the
      potential synergy of the combined materials. Here we fabricate novel
      thermal/electrical responsive photonic composite films combining cellulose
      nanocrystals (CNC) with a low molecular weight nematic liquid crystal (NLC), 4'
      (hexyloxy)-4-biphenylcarbonitrile (HOBC). The obtained composite material
      combines both intense structural coloration of photonic cellulose and thermal and
      conductive properties of NLC. Scanning electron microscopy (SEM) results
      confirmed that liquid crystals coated CNC films maintain chiral nematic structure
      characteristic of CNC film and simultaneously, transversal cross-section scanning
      electron microscopy images indicated penetration of liquid crystals through the
      CNC layers. Investigated composite film maintain NLC optical properties being
      switchable as a function of temperature during heating/cooling cycles. The
      relationship between the morphology and thermoresponsive in the
      micro/nanostructured materials was investigated by using transmission optical
      microscopy (TOM). Conductive response of the composite films was proved by
      Electrostatic force microscopy (EFM) measurement. Designed thermo- and electro
      responsive materials open novel simple pathway of fabrication of CNC-based
      materials with tunable properties.

PMID- 28457460
TI  - Functional group analysis of starches reacted with urea-phosphoric acid
      Correlation of wet chemical measures with FT Raman spectroscopy.
AB  - Because the degree of substitution (DS) of chemically modified starches strongly
      affects their physicochemical properties and applications, rapid techniques for
      its determination are crucial. In the present work, ammonium starch phosphates
      carbamates (SPC) were obtained by reacting starch with urea-phosphoric acid. DS
      of phosphate (DSP), carbamate (DSC), and ammonium groups (DSNH4+) and contents of
      non-hydrolyzable amides (Nnh) of SPC were determined using the
      vanadomolybdophosphoric acid and saponification methods, respectively. It was the
      aim to investigate the extent to which Raman features of SPC relate to their DS
      values of different functional groups as obtained by wet chemistry. Strong linear
      correlations (R2=0.967...0.995) were found between DSP, DSNH4+, and the degree of
      substitution of urea (DSurea) and Raman signals at 820, 1710 and 1015cm-1. Thus,
      with appropriate calibration, Raman spectroscopy is a promising tool for the
      simultaneous and rapid determination of the level of phosphorylation and the
      ammonium and urea contents of SPC.

PMID- 28457461
TI  - A tale of two pectins: Diverse fine structures can result from identical
      processive PME treatments on similar high DM substrates.
AB  - The effects of a processive pectin-methylesterase (PME) treatment on two
      different pectins, both possessing a high degree of methylesterification (DM),
      were investigated. While the starting samples were purportedly very similar in
      fine structure, the intermolecular DM distributions arising from their PME
      treatments were strikingly different. Herein, a simulation that illuminates the
      origin of this phenomenon is described. It is concluded that: (1) very different
      low-DM samples (with the same average DM) can be generated using the same
      processive PME, simply by a judicious choice of the high DM starting material;
      (2) observing the intermolecular DM distribution of the products of processive
      PME-processing is an extremely sensitive discriminator of the fine structure of
      high DM starting materials; and (3) for PMEs with unknown action patterns the
      processive nature of the enzyme is most simply revealed by studying the changes
      it induces in the intermolecular DM distribution of very-highly-methylesterified
      homogalacturonans.

PMID- 28457462
TI  - Characterization of methacrylated alginate and acrylic monomers as versatile
      SAPs.
AB  - Superabsorbent polymers (SAPs) based on polysaccharides, especially alginate,
      could offer a valuable solution in a plethora of applications going from drug
      delivery to self-healing concrete. This has already been proven with both calcium
      alginate and methacrylated alginate combined with acrylic acid. In this
      manuscript, the effect of varying the degree of methacrylation and use of a
      combination of acrylic acid and acrylamide is investigated to explore the effects
      on the relevant SAP characteristics. The materials showed high gel fractions and
      a strong swelling capacity up to 630gwater/gSAP, especially for superabsorbent
      polymers with a low degree of substitution. The SAPs also showed only a limited
      hydrolysis in aqueous and cement filtrate solutions.

PMID- 28457463
TI  - Effect of reprocessing cycles on the degradation of PP/PBAT-thermoplastic starch
      blends.
AB  - The solid waste management problems caused by the accumulation of plastics
      require measures to mitigate the environmental damage, and mechanical recycling
      of plastics is among the possible solutions. In this context, the present study
      aimed to evaluate the effects of mechanical recycling on the properties of a
      polypropylene/poly(butylene adipate co-terephthalate)-thermoplastic starch blend
      (PP/PBAT-Thermoplastic starch blend) when it was subjected to seven reprocessing
      cycles by a single-screw extruder. The observations by infrared spectroscopy
      indicated that the chemical structures of the blend and the polypropylene matrix
      did not present significant changes with the reprocessing cycles. The X-ray
      diffraction analyses showed that the PP crystals were most affected when
      reprocessed in their pure form. The observations by thermogravimetry and
      differential scanning calorimetry indicated that the thermal stability of the
      blend was higher than that of polypropylene during the extrusion cycles. The
      scanning electron microscopy images indicated a weak interfacial interaction
      between the components of the blend, and the mechanical properties showed that
      the reprocessing improved the elasticity modulus and yield stress, with a
      consequential decrease of the impact strength.

PMID- 28457464
TI  - Alginate based nanocomposite for microencapsulation of probiotic: Effect of
      cellulose nanocrystal (CNC) and lecithin.
AB  - Probiotic (Lactobacillus rhamnosus ATCC 9595) was encapsulated in alginate-CNC
      lecithin microbeads to produce nutraceutical microcapsules. Addition of CNC and
      lecithin in alginate microbeads (ACL-1) improved the viability of L. rhamnosus
      during gastric passage and storage. The compression strength of the freeze-dried
      ACL-1 microbeads improved 40% compared to alginate microbeads alone. Swelling
      studies revealed that addition of CNC and lecithin in alginate microbeads
      decreased (around 47%) the gastric fluid absorption but increased the dissolution
      time by 20min compared to alginate microbeads (A-0). During transition through
      the gastric passage, the viability of L. rhamnosus in dried ACL-1 microbeads was
      increased 37% as compared to A-0 based beads. At 25 and 4 degrees C storage
      conditions, the viability of L. rhamnosus encapsulated in ACL-1 microbeads
      decreased by 1.23 and 1.08 log respectively, whereas the encapsulation with A-0
      microbeads exhibited a 3.17 and 1.93 log reduction respectively.

PMID- 28457465
TI  - Starch nanoparticles resulting from combination of dry heating under mildly
      acidic conditions and homogenization.
AB  - To modify starch granular structure, normal maize starch was subjected to dry
      heating with various amounts of 1.0M HCl (1.2, 1.4 or 1.6mL) and different
      treatment times (2, 4 or 8h). For all reaction conditions, at least 80% of the
      starch substance was recovered, and amylose and amylopectin B1 chains were
      preferentially cleaved. As acidic condition and/or treatment time increased, the
      treated granules were readily fragmented by homogenization. The treatment
      appeared to alter short-range crystalline structure (FT-IR), but long-range
      crystalline structure (XRD) remained intact. Homogenization for 60min fragmented
      the treated starch granules (subjected to reaction condition of 1.4mL/4h,
      1.6mL/2h, and 1.6mL/4h) into nanoparticles consisting of individual platelet-like
      and spherical particles with diameters less than 100nm. However, the
      fragmentation caused obvious damage in the long-range crystalline structure of
      starch nanoparticles, while the short-range chain associations remained
      relatively intact.

PMID- 28457466
TI  - Effects of carboxylation of the side chains on the order-disorder transition in
      aqueous solution of schizophyllan, a triple helical polysaccharide.
AB  - Schizophyllan and scleroglucan are water-soluble polysaccharides having repeating
      units consisting of three beta-1,3-linked glucose residues in the main chain and
      a single beta-1,6-linked glucose residue as the side chain. This polysaccharide
      dissolves as a triple helix in an aqueous solution and shows a cooperative order
      disorder transition between the side chain and solvent molecules while retaining
      the triple helical conformation. Periodate and subsequent chlorite oxidations
      selectively modify the side chain glucose to provide the corresponding
      dicarboxylate units. Optical rotation measurements and differential scanning
      calorimetry were performed on carboxylated schizophyllan/scleroglucan ('sclerox')
      samples to investigate the effects of the degree of carboxylation on the order
      disorder transition in deuterium oxide with 0.1M NaCl. The transition curves for
      the sclerox samples are strongly dependent on the degree of carboxylation. The
      modified side chains cannot take the ordered structure, resulting in a reduction
      of the transition enthalpy. The transition temperature for carboxylated
      schizophyllan becomes lowered and the transition curve broadens with increasing
      the degree of carboxylation. The permanent disordered units are included in a
      trimer by the carboxylation to inhibit a long sequence of the ordered units.

PMID- 28457467
TI  - Isolation and characterisation of nanoparticles from tef and maize starch
      modified with stearic acid.
AB  - Nanoparticles were isolated from tef and maize starch modified with added stearic
      acid after pasting at 90 degrees C for 130min. This was followed by thermo-stable
      alpha-amylase hydrolysis of the paste. The resultant residues were then
      characterized using X-ray diffraction (XRD), differential scanning calorimetry
      (DSC), dynamic laser scattering particle size distribution (DLPSD), atomic force
      microscopy (AFM) and high-resolution transmission electron microscopy (HRTEM).
      XRD and DSC showed that the isolated residues consisted of amylose-lipid
      complexes. These complexes were type II with melting temperature above 104
      degrees C. DLPSD, AFM and HRTEM showed that the isolated tef and maize starch
      residues consisted of nanoparticles which became more distinct with increased
      hydrolysis time. The isolated tef and maize nanoparticles had distinct particles
      of about 3-10nm and 2.4-6.7nm, respectively and the yield was about 24-30%. The
      results demonstrated that distinct (physically separate) nanoparticles of less
      than 10nm can be isolated after formation during pasting of tef and maize starch
      with stearic acid. The production and isolation of the nanoparticles uses green
      chemistry principles and these nanoparticles can be used in food and non-food
      systems as nanofillers.

PMID- 28457468
TI  - Insights into cell wall structure of Sida hermaphrodita and its influence on
      recalcitrance.
AB  - The perennial plant Sida hermaphrodita (Sida) is attracting attention as
      potential energy crop. Here, the first detailed view on non-cellulosic Sida cell
      wall polysaccharide composition, structure and architecture is given. Cell walls
      were prepared from Sida stems and sequentially extracted with aqueous buffers and
      alkali. The structures of the quantitatively predominant polysaccharides present
      in each fraction were determined by biochemical characterization, glycome
      profiling and mass spectrometry. The amounts of glucose released by Accellerase
      1500(r) treatment of the cell wall and the cell wall residue remaining after each
      extraction were used to assess the roles of pectin and hemicellulose in the
      recalcitrance of Sida biomass. 4-O-Methyl glucuronoxylan with a low proportion of
      side substitutions was identified as the major non-cellulosic glycan component of
      Sida stem cell walls. Pectic polysaccharides and xylans were found to be
      associated with lignin, suggesting that these polysaccharides have roles in Sida
      cell wall recalcitrance to enzymatic hydrolysis.

PMID- 28457469
TI  - Severe bleeding caused by giant gastrointestinal stromal tumor of the jejunum.

PMID- 28457470
TI  - Where is haemorrhoidal surgery heading?

PMID- 28457471
TI  - Response to Omalizumab in Solar Urticaria: Report of 3 Cases.
AB  - We report 3 cases of solar urticaria in which there was no response or limited
      response to first-line treatments with high-dose H1 antihistamines or
      phototherapy. The patients were then treated with omalizumab. Symptoms improved
      in 2 patients, whose tolerance to sunlight increased considerably; quality of
      life clearly improved for 1 of these patients. The third experienced no
      improvement and developed a mild local reaction to the injected medication. We
      conclude that omalizumab may offer a potentially safe, useful alternative for
      patients with solar urticaria who do not respond to conventional therapy.

PMID- 28457473
TI  - Polymorphisms in POLG were associated with the prognosis and mtDNA content in
      hepatocellular carcinoma patients.
AB  - BACKGROUND: POLG is a gene that codes for the catalytic subunit of the
      mitochondrial DNA polymerase, which is involved in the replication of
      mitochondrial DNA. Genetic variants in mitochondrial DNA polymerase-gamma (POLG)
      have been associated with several malignancies. However, as an important
      metabolic tissue, association between genetic polymorphisms of POLG and the
      prognosis and mitochondrial DNA (mtDNA) content in hepatocellular carcinoma (HCC)
      remains unknown. Here we investigated the association between in POLG with the
      prognosis and mitochondrial DNA (mtDNA) content in hepatocellular carcinoma
      (HCC). METHODS: Three nucleotide polymorphisms (SNPs) of rs1061316, rs2247233 and
      rs758130 in POLG were examined in 416 patients from two cohorts undergoing
      transcatheter arterial chemoembolization treatment. Leukocyte mtDNA content from
      216 patients in cohort 2 was measured using a real-time PCR-based method. The
      association of SNPs with prognosis and of mtDNA content of patients was analyzed.
      RESULTS: The rs758130 in POLG gene was significantly associated with the
      prognosis of patients in a dose-dependent manner. Moreover, GG genotype in
      rs1061316 showed significantly high mtDNA content, an indicator of better
      prognosis. CONCLUSIONS: Our study for the first time demonstrates that rs1061316
      and rs758130 in POLG is associated with the prognosis and leukocyte mtDNA content
      in HCC patients.

PMID- 28457474
TI  - [Some reflections about the recent paper published by Tomasetti, Li and
      Vogelstein in Science].

PMID- 28457472
TI  - Duplicated Enhancer Region Increases Expression of CTSB and Segregates with
      Keratolytic Winter Erythema in South African and Norwegian Families.
AB  - Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder
      characterized by recurrent episodes of palmoplantar erythema and epidermal
      peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South
      African families. Using targeted resequencing of the KWE critical region in five
      South African families and SNP array and whole-genome sequencing in two Norwegian
      families, we identified two overlapping tandem duplications of 7.67 kb (South
      Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease
      and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine
      protease involved in keratinocyte homeostasis. Included in the 2.62 kb
      overlapping region of these duplications is an enhancer element that is active in
      epidermal keratinocytes. The activity of this enhancer correlated with CTSB
      expression in normal differentiating keratinocytes and other cell lines, but not
      with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and
      immunohistochemistry of the palmar epidermis demonstrated significantly increased
      expression of CTSB, as well as stronger staining of cathepsin B in the stratum
      granulosum of affected individuals than in that of control individuals. Analysis
      of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from
      MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in
      South African and Norwegian families is caused by tandem duplications in a non
      coding genomic region containing an active enhancer element for CTSB, resulting
      in upregulation of this gene in affected individuals.

PMID- 28457475
TI  - How can we be more "deliberate" in training surgeons?

PMID- 28457476
TI  - Mechanisms underlying methamphetamine-related dental disease.
AB  - BACKGROUND: The authors clarified the causal mechanisms underlying the high
      prevalence of dental disease encountered in people who habitually use
      methamphetamine (meth). METHODS: Using a stratified sampling approach, the
      authors conducted comprehensive oral examinations and psychosocial assessments
      for 571 study participants who used meth. Three calibrated dentists, who used
      National Health and Nutrition Examination Survey (NHANES) protocols,
      characterized the study participants' dental disease. The authors also collected
      data related to study participants' history of meth use and other attributes
      linked to dental disease. RESULTS: Study participants who used meth manifested
      higher rates of xerostomia and caries experience compared with NHANES control
      participants. Participants who used meth had a higher level of daily consumption
      of sugary beverages compared with NHANES control participants. Smoking meth did
      not increase caries experience over other modes of intake. Dental hygiene was a
      significant determinant of dental health outcomes. CONCLUSIONS: Mode of intake
      and frequency of meth use have a minimal impact on dental health outcomes.
      Behaviors, such as sugary beverage consumption and poor oral hygiene, better
      explain dental health outcomes. PRACTICAL IMPLICATIONS: Having a better
      understanding of the causal mechanisms of "meth mouth" sets the stage for
      clinicians to provide more personalized interventions and management of dental
      disease in people who use meth.

PMID- 28457478
TI  - Mechanical Concepts Applied in Congenital Heart Disease and Cardiac Surgery.
AB  - All biological processes are governed by principles of physics that dictate the
      pathophysiology and even the treatment of congenital heart diseases. In this
      review, basic concepts such as flow, pressure, resistance, and velocity are
      introduced, followed by more complex laws that describe the relationship between
      these variables and the disease processes. Finally, physical phenomena such as
      turbulence, steal and runoff phenomenon, and energy loss are discussed. By
      application of these principles, one can accurately quantify modifications
      undertaken to treat diseases, for example, the size of a patch that augments a
      vessel and the angle of an anastomosis to allow a certain flow.

PMID- 28457477
TI  - Parental perceptions and acceptance of silver diamine fluoride staining.
AB  - BACKGROUND: The caries arrest that can be achieved by using silver diamine
      fluoride (SDF) offers a minimally invasive and inexpensive alternative to
      traditional restorative caries treatment. The authors evaluated how the dentinal
      staining that is associated with SDF influences the acceptance of this treatment
      among parents of young children in the New York City metropolitan area. METHODS:
      The authors invited the parents of children who had experienced dental caries and
      who had appointments at the New York University Pediatric Dentistry Clinic and at
      several private clinics in New Jersey to participate in a Web-based survey
      designed to assess parents' demographics, perceptions of photographs of SDF
      treated carious teeth, and acceptability of treatment in different behavior
      management scenarios. RESULTS: Ninety-eight mothers and 22 fathers from diverse
      backgrounds participated. Most parents (67.5%) judged SDF staining on the
      posterior teeth to be esthetically tolerable, but only 29.7% of parents made this
      same judgment about anterior teeth (P < .001). In the absence of their child
      having behavioral barriers to conventional restorations, 53.6% of parents
      reported that they were likely to choose SDF to treat their child's posterior
      teeth, but only 26.9% of parents were likely to choose SDF to treat their child's
      anterior teeth. As the number of children's behavioral barriers increased, so did
      the parents' level of acceptance. In extreme cases, in which parents had to
      decide whether their children should undergo general anesthesia during treatment,
      parents' acceptance rate of SDF as a treatment method increased to 68.5% on
      posterior teeth and to 60.3% on anterior teeth. Parents' acceptance of the
      treatment also varied according to their socioeconomic status. CONCLUSIONS:
      Staining on posterior teeth was more acceptable than staining on anterior teeth.
      Although staining on anterior teeth was undesirable, most parents preferred this
      option to advanced behavioral techniques such as sedation or general anesthesia.
      PRACTICAL IMPLICATIONS: Clinicians need to understand parental sensitivities
      regarding the staining effect of SDF to plan adequately for the use of SDF as a
      method of caries management in pediatric patients.

PMID- 28457479
TI  - X-LAG: How did they grow so tall?
AB  - X-linked acrogigantism (XLAG) is a new, pediatric-onset genetic syndrome, due to
      Xq26.3 microduplications encompassing the GPR101 gene. XLAG has a remarkably
      distinct phenotype with disease onset occurring before the age of 5 in all cases
      described to date, which is significantly younger than in other forms of
      pituitary gigantism. These patients have mixed GH and prolactin positive adenomas
      and/or mixed-cell hyperplasia and highly elevated levels of GH/IGF-1 and
      prolactin. Given their particularly young age of onset, the significant GH
      hypersecretion can lead to a phenotype of severe gigantism with very advanced age
      specific height Z-scores. If not adequately treated in childhood, this condition
      results in extreme final adult height. XLAG has a clinical course that is highly
      similar to some of the tallest people with gigantism in history.

PMID- 28457480
TI  - How should we investigate children with growth failure?
AB  - The early diagnosis of short stature is essential for effective management and
      treatment. Investigations for children with growth failure are required to
      distinguish between idiopathic short stature due to physiological variants
      (familial short stature, and constitutional delays of growth and puberty, or
      both), primary causes of short stature, such as syndromic and/or genetic defects
      and skeletal dysplasia, and secondary growth deficits due to endocrine or other
      chronic disorders such as celiac disease, Crohn's disease, malnutrition, renal,
      anorexia nervosa or other chronic diseases.

PMID- 28457481
TI  - Have we finally solve the enigma of the small size of Pygmies?
AB  - Pygmies are considered to be among the smallest humans. Their small size is an
      enigma that has puzzled numerous scientists. Many data have been collected
      concerning their clinical and biological phenotypes, genetics, lifestyle, culture
      and environment, but the reasons for their small size remain a matter of debate.
      Is it an adaptation to life in the tropical forest, an impact of the environment,
      an usual genetic feature or a mixture of these factors? Studies of the
      somatotropic axis have revealed that serum IGF-1 concentrations are low in this
      population, probably due to an impairment of the GH receptor. However, many
      uncertainties remain, and further hormonal, genetic and epigenetic studies will
      be required in the framework of multidisciplinary studies.

PMID- 28457483
TI  - Pathways towards the proliferation of avoidance in anxiety and implications for
      treatment.
AB  - Avoidance is a key symptom of anxiety disorders. Maladaptive avoidance impairs
      general functioning acutely and maintains chronic anxiety. A better understanding
      of the mechanisms that elicit and maintain excessive avoidance might provide
      opportunities to improve treatment. Here, we discuss pathways through which
      avoidance might get amplified in the context of anxiety disorders: 1) increased
      threat appraisal; 2) enhanced threat avoidance tendencies; 3) impaired regulation
      of avoidance; 4) habitual avoidance; and 5) attempts at increasing psychological
      distance. Novel strategies for reducing avoidance are considered. These include
      memory reconsolidation interference, retraining of avoidance tendencies,
      mindfulness training and habit disruption approaches. Throughout the paper, we
      highlight a number of suggestions for future research on avoidance and how to
      achieve lasting behavior change.

PMID- 28457482
TI  - Aging effects on T-bet expression in human B cell subsets.
AB  - In order to compare human and mouse B cell subset markers, we evaluated T-bet
      expression in human B cell subsets from individuals of different ages. We found T
      bet expressed in unstimulated memory more than naive B cells, and more in young
      individuals. TLR7 stimulation up-regulated T-bet in all B cell subsets from young
      and elderly individuals, and more in the elderly. By fold-increase the best
      effect was seen in subsets of the elderly and especially in those that undergo
      class switch (naive and IgM). We also evaluated CD11c expression, as T-bet+CD11c+
      B cells are expanded in healthy elderly individuals and also in patients with
      autoimmunity. Similar to T-bet, CD11c expression was higher in memory than in
      naive B cells, but no differences were observed between young and elderly
      individuals. After TLR7 stimulation, CD11c increases in all B cell subsets
      (especially in naive and IgM) from the elderly.

PMID- 28457484
TI  - Temporal dynamics of relief in avoidance conditioning and fear extinction:
      Experimental validation and clinical relevance.
AB  - The learning principles that guide the acquisition and extinction of avoidance
      are not fully understood. We developed a novel paradigm to study the temporal
      dynamics of relief, a putative reinforcer of avoidance, and the recovery of fear
      and avoidance following extinction. During conditioning, the avoidance action
      canceled the aversive unconditional stimulus (US), without terminating the
      predictive conditional stimulus (CS). Relief pleasantness was rated after fixed
      CS offsets, when US omission occured. Avoidance was effective to one CS, but not
      to another, to track stimulus-specific avoidance learning. Fear was extinguished
      under response prevention in a separate context. Recovery tests took place 24 h
      later, in both contexts and with a monetary cost added to the avoidance action.
      We found that avoidance gradually became stimulus-specific during conditioning,
      but hardly recovered during delayed testing. Across all phases, initial omissions
      of the aversive US triggered relief that gradually declined over consecutive
      omissions, in line with a theoretical prediction error signal. Participants that
      scored low on distress tolerance, however, displayed sustained levels of relief
      over continuous omissions. We propose that such forms of sustained relief may
      produce over-reinforcement of foregoing avoidance actions and promote the
      development of pathological avoidance. The current paradigm represents an
      efficacious tool to study the temporal dynamics of relief across avoidance
      learning and fear extinction and to characterize relief dysregulations in
      relation to psychopathology.

PMID- 28457485
TI  - Motor-Activity Markers of Circadian Timekeeping Are Related to Ketamine's Rapid
      Antidepressant Properties.
AB  - BACKGROUND: The rapid clinical antidepressant effects of the glutamatergic
      modulator ketamine may be due to its ability to restore synaptic plasticity and
      related effects on sleep-wake and circadian systems. Preclinical studies indicate
      that ketamine alters expression of circadian clock-associated molecules, and
      clinical studies of ketamine on plasticity-related biomarkers further suggest an
      association with sleep slow waves and sleep homeostasis. METHODS: Wrist-activity
      monitors were used to examine the pharmacologic and rapid antidepressant effects
      of ketamine on markers of circadian timekeeping (amplitude and timing) in mood
      disorders. Circadian amplitude and timing of activity at baseline, postinfusion
      day 1 (D1), and day 3 (D3) were measured in 51 patients with major depressive
      disorder or bipolar disorder. RESULTS: Compared with either placebo or baseline,
      a mood-independent decrease of the central circadian value (mesor) was present on
      D1 after ketamine treatment. Mood-associated circadian effects between rapid (D1)
      responders and nonresponders were found at baseline, D1, and D3. At baseline, a
      phase-advanced activity pattern and lower mesor distinguished subsequent
      responders from nonresponders. On D1, ketamine nonresponders had a lower mesor
      and a blunted 24-hour amplitude relative to baseline. On D3, patients with a
      persisting clinical response exhibited a higher amplitude and mesor compared with
      nonresponders. CONCLUSIONS: The findings are the first to demonstrate an
      association between ketamine's clinical antidepressant effects and circadian
      timekeeping. The results suggest that traitlike circadian activity patterns
      indicate rapid mood response to ketamine, and that mediators of continuing
      ketamine-induced mood changes include altered timing and amplitude of the
      circadian system.

PMID- 28457487
TI  - One Health Approach to Preventing Obesity in People and Their Pets.

PMID- 28457488
TI  - Determination of gas-liquid partition coefficients of several organic solutes in
      trihexyl(tetradecyl)phosphonium bromide using capillary gas chromatography
      columns.
AB  - In this paper, we report gas-liquid partition constants for thirty-five volatile
      organic solutes in the room temperature ionic liquid
      trihexyl(tetradecyl)phosphonium bromide measured by gas-liquid chromatography
      using capillary columns. The relative contribution of gas-liquid partition and
      interfacial adsorption to retention was evaluated through the use of columns with
      different the phase ratio. Four capillary columns with exactly known phase ratios
      were constructed and employed to measure the solute retention factors at four
      temperatures between 313.15 and 343.15K. The partition coefficients were
      calculated from the slopes of the linear regression between solute retention
      factors and the reciprocal of phase ratio at a given temperature according to the
      gas-liquid chromatographic theory. Gas-liquid interfacial adsorption was detected
      for a few solutes and it has been considered for the calculations of partition
      coefficient. Reliable solute's infinite dilution activity coefficients can be
      obtained when retention data are determined by a unique partitioning mechanism.
      The partial molar excess enthalpies at infinite dilution have been estimated from
      the dependence of experimental values of solute activity coefficients with the
      column temperature. A thorough discussion of the uncertainties of the
      experimental measurements and the main advantages of the use of capillary columns
      to acquire the aforementioned relevant thermodynamic information was performed.

PMID- 28457486
TI  - Vaccination against Louping Ill Virus Protects Goats from Experimental Challenge
      with Spanish Goat Encephalitis Virus.
AB  - Spanish goat encephalitis virus (SGEV) is a recently described member of the
      genus Flavivirus belonging to the tick-borne encephalitis group of viruses, and
      is closely related to louping ill virus (LIV). Naturally acquired disease in
      goats results in severe, acute encephalitis and 100% mortality. Eighteen goats
      were challenged subcutaneously with SGEV; nine were vaccinated previously against
      LIV and nine were not. None of the vaccinated goats showed any clinical signs of
      disease or histological lesions, but all of the non-vaccinated goats developed
      pyrexia and 5/9 developed neurological clinical signs, primarily tremors in the
      neck and ataxia. All non-vaccinated animals developed histological lesions
      restricted to the central nervous system and consistent with a lymphocytic
      meningomyeloencephalitis. Vaccinated goats had significantly (P <0.003) greater
      concentrations of serum IgG and lower levels of IgM (P <0.0001) compared with
      unvaccinated animals. SGEV RNA levels were below detectable limits in the
      vaccinated goats throughout the experiment, but increased rapidly and were
      significantly (P <0.0001) greater 2-10 days post challenge in the non-vaccinated
      group. In conclusion, vaccination of goats against LIV confers highly effective
      protection against SGEV; this is probably mediated by IgG and prevents an
      increase in viral RNA load in serum such that vaccinated animals would not be an
      effective reservoir of the virus.

PMID- 28457489
TI  - One pot synthesis of carboxyl functionalized-polyhedral oligomeric siloxane based
      monolith via photoinitiated thiol-methacrylate polymerization for nano
      hydrophilic interaction chromatography.
AB  - A hybrid monolith exhibiting almost retention independent separation performance
      in hydrophilic interaction chromatography (HILIC) was obtained by one-pot
      photoinitiated thiol-methacrylate polymerization. Polyhedral oligomeric
      silsesquioxane containing methacrylate units (POSS-MA) was used as the main
      monomer and crosslinking agent, together with a hydrophilic ligand with two
      carboxyl groups, mercaptosuccinic acid (MSA) as the thiol agent and
      chromatographic ligand. The isocratic separation of nucleosides, nucleotides and
      organic acids on MSA attached-poly(POSS-MA) monolith was investigated in HILIC
      mode. The van-Deemter plots for obtained for nucleosides, nucleotides and benzoic
      acids clearly showed that there were two regions in each graph with two different
      slopes in the studied range of linear flow rate (i.e. 0.2-4.3mm/s). The slope of
      plate height-linear velocity curve was so small in the low linear velocity region
      between 0.2-2.1mm/s while the slope in high linear velocity region between 2.1
      4.3mm/s was so higher with respect to the first region. The van-Deemter plots
      sketched for all analyte grous used in HILIC mode obeyed this tendency Almost
      "retention independent plate height behavior" was demonstrated in HILIC, using
      nucleotides, nucleotides or benzoic acids as the analytes in the linear velocity
      range of 0.2-2.1mm/s. This behavior was explained by the porous structure of the
      synthesized monolith facilitating the convective transport of analytes. The
      variation of plate height was not retention-independent within high linear
      velocity range (>3.2mm/s) when nucleosides were separated in HILIC mode.

PMID- 28457490
TI  - Disorders of motor neurons manifested by hyperactivity.
AB  - Neuronal and/or axonal hyperactivity and hyperexcitability is an important
      feature of motor neuron diseases. It results clinically in cramps and
      fasciculations. It is not specific to motor neuron diseases, and can occur in
      healthy subjects, as well as in various pathologies of the peripheral nervous
      system, including nerve hyperexcitability syndromes. Hyperexcitability plays an
      important and debated role in the pathophysiology of motor neuron diseases,
      especially in amyotrophic lateral sclerosis (ALS). The mechanisms causing
      hyperexcitability are not yet clearly identified. While most studies favor a
      distal axonal origin site of fasciculations, some of the fasciculations could be
      of cortical origin. The consequences of hyperexcitability are also discussed,
      whether it is rather protective or deleterious in the disease course.
      Fasciculations are depicted both clinically and using electromyogram, and more
      recently the interest of ultrasound has been highlighted. The importance of
      fasciculation potentials in the diagnosis of ALS led to changes in
      electrophysiological criteria at Awaji consensus conference. The contribution of
      these modifications to ALS diagnosis has been the subject of several studies. In
      clinical practice, it is necessary to distinguish fasciculations potentials of
      motor neuron disease from benign fasciculations. In most studies of fasciculation
      potentials in ALS, the presence of complex fasciculation potentials appears to be
      relevant for the diagnosis and the prognosis of the disease.

PMID- 28457491
TI  - Chemoimmunotherapeutic effect of combined treatment with ex vivo generated
      antigen-presenting immune cells and conventional antitumor agents in a mouse
      neuroblastoma model.
AB  - PURPOSE: Combining antitumor immunotherapy with conventional intensive multimodal
      therapy may be considered for advanced neuroblastoma. We investigated combination
      therapy with ex vivo generated immunostimulatory cells and intraperitoneal
      doxorubicin. METHODS: Immunogenic death of neuro-2a neuroblastoma cells was
      induced by doxorubicin or cisplatin (negative control). Mouse bone marrow cells
      were cultured with granulocyte-macrophage colony-stimulating factor, followed by
      addition of doxorubicin-killed neuro-2a cells with or without interleukin-4
      and/or CpG-oligodeoxynucleotide to induce immunostimulatory cells. CD8alpha+
      lymphocytes were cocultured with killed neuro-2a cells and immunostimulatory
      cells, and interferon-gamma was measured in the supernatant. Furthermore, female
      A/J mice were injected with viable neuro-2a cells, followed by immunostimulatory
      cells and doxorubicin. Then intraabdominal tumor nodules were evaluated. RESULTS:
      Bone marrow-derived immunostimulatory cells only promoted interferon-gamma
      production by CD8alpha+ lymphocytes after first being stimulated by doxorubicin
      killed neuro-2a cells and interleukin-4, followed by CpG-oligodeoxynucleotide.
      These cells had a surface antigen expression profile compatible with activated
      dendritic cells and suppressed tumors in mice intravenously injected with neuro
      2a cells. Despite a similar surface antigen profile, the in vivo antitumor effect
      was stronger after injection of immunostimulatory cells induced by doxorubicin
      killed neuro-2a cells compared with cells induced by cisplatin-killed neuro-2a
      cells. Moreover, interferon-gamma production was greater when CD8alpha+
      lymphocytes were cocultured with doxorubicin-killed neuro-2a cells and
      immunostimulatory cells rather than with cisplatin-killed cells. CONCLUSION:
      Cells with antitumor activity can be induced from bone marrow cells. Combining
      such cells with doxorubicin may activate antitumor immunity in tumor-bearing
      mice. Interactions between induced immunostimulatory cells and conventional
      chemotherapy might be important for antitumor immunity.

PMID- 28457492
TI  - Erratum to "Clinical course and predictive factors for complication of inferior
      vena cava filters" [Thromb. Res. 133/4 (2014) 538-543].

PMID- 28457493
TI  - Nursing home care trajectories for older adults following in-hospital palliative
      care consultation.
AB  - Palliative care consultation (PCC) during hospitalization is increasingly common
      for older adults with life-limiting illness discharged to nursing homes. The
      objective of this qualitative descriptive study was to describe the care
      trajectories and experiences of older adults admitted to a nursing home following
      a PCC during hospitalization. Twelve English-speaking adults, mean age 80 years,
      who received a hospital PCC and discharge to a nursing home without hospice. Data
      were collected from medical records at five time points from hospital discharge
      to 100 days after nursing home admission and care trajectories were mapped.
      Interviews (n = 15) with participants and surrogates were combined with each
      participant's medical record data. Content analysis was employed on the combined
      dataset. All PCC referrals were for goals of care conversations during which the
      PCC team discussed poor prognosis. All participants were admitted to a nursing
      home under the Medicare skilled nursing facility benefit. Seven were
      rehospitalized; six of the 12 died within 6 weeks of initial nursing home
      admission. The two care trajectories were Focus on Rehabilitative Care and
      Comfort Care Continuity. There was a heavy emphasis on recovering functional
      status through rehabilitation and skilled nursing care, despite considerable
      symptom burden and poor prognosis. Regardless of PCC with recommendations for
      palliative interventions, frail older adults with limited life expectancy and
      their family caregivers often perceive that rehabilitation will improve physical
      function. This perception may contribute to inappropriate, ineffective care. More
      emphasis is needed to coordinate care between PCC recommendations and post-acute
      care.

PMID- 28457494
TI  - Vitamin D Status and the Host Resistance to Infections: What It Is Currently
      (Not) Understood.
AB  - PURPOSE: Vitamin D is increasingly thought to play a role in regulating immunity.
      This comprehensive review updates the current understanding regarding ways in
      which we believe that vitamin D regulates responsiveness of the immune system and
      how serum status modulates the host defense against pathogens. METHODS: The
      literature was searched by using PubMed and Scopus with the following key words:
      vitamin D, immunity, innate and adaptive immunity, infectious disease, and
      vaccine response. FINDINGS: Vitamin D deficiency remains a major public health
      concern worldwide. The overall body of evidence confirms that vitamin D plays an
      important role in modulating the immune response to infections. Epidemiologic
      studies suggest a clear association between vitamin D deficiency and
      susceptibility to various pathogens. However, translation of vitamin D use into
      the clinic as a means of controlling infections is fraught with methodologic and
      epidemiologic challenges. The recent discovery of alternative activation
      pathways, different active forms of vitamin D, and possible interaction with non
      vitamin D receptors provide further complications to an already complex
      interaction between vitamin D and the immune system. Moreover, it has become
      apparent that the individual responsiveness to supplementation is more dynamic
      than presumed from the static assessment of 25-hydroxy vitamin D status.
      Furthermore, the epigenetic response at the level of the individual to
      environmental changes and lifestyle or health conditions provides greater
      variation than those resulting from vitamin D receptor polymorphisms.
      IMPLICATIONS: To understand the future of vitamin D with respect to clinical
      applications in the prevention and better control of infectious diseases, it is
      necessary to determine all aspects of vitamin D metabolism, as well as the
      mechanisms by which active forms interact with the immune system globally. For
      the most part, we are unable to identify tissue-specific applications of
      supplementation except for those subjects at high risk of osteomalacia and
      osteoporosis.

PMID- 28457495
TI  - Adjuvant intravesical treatment for nonmuscle invasive bladder cancer: The
      importance of the strain and maintenance.
AB  - BACKGROUND AND OBJECTIVE: Intravesical Bacille Calmette-Guerin (BCG) is essential
      for preventing the recurrence and progression of superficial bladder tumours. The
      aim of our study was to compare the efficacy and toxicity of the Connaught and
      Tice strains, as well as the importance of the maintenance regimen. MATERIAL AND
      METHODS: We retrospectively reviewed 110 patients with superficial bladder
      tumours who underwent adjuvant endovesical treatment. The patients were
      distributed into 3 groups, based on whether the treatment was with the Connaught
      strain, the Tice strain or both sequentially. We calculated the relapse-free
      survival rate in each group and compared the patients who completed the
      maintenance treatments against those who did not. To identify the predictors of
      relapse, we performed a multivariate analysis. We also assessed the toxicity by
      analysing the onset of BCGitis, urinary urgency, fever, urinary tract infection
      and treatment withdrawing due to adverse effects. RESULTS: We found no
      differences in the efficacy parameters. The patients in the Connaught group
      completed the maintenance to a lesser extent (38.4 vs. 72% for the Tice group and
      76.3% for both groups; P=.010). The patients who completed the maintenance had
      better relapse-free survival at 60 months (88.5 vs. 74.2%; P=.036), regardless of
      the strain employed. The multivariate analysis identified a size larger than 3cm,
      more than 3 implants and not completing the maintenance as risk factors of
      relapse. The patients with the Connaught strain had higher rates of BCGitis, with
      no differences in the other events studied. CONCLUSION: Completing the
      maintenance phase is essential, regardless of the strain employed. The Connaught
      strain has a greater risk of BCGitis, and a sequential regimen could be useful in
      certain scenarios.

PMID- 28457496
TI  - Ultrasound-guided percutaneous radiofrequency ablation for treating small renal
      masses.
AB  - INTRODUCTION: The objective of this study was to analyse and assess the
      experience with radiofrequency ablation of small renal masses using a contrast
      enhanced, ultrasound-guided percutaneous approach for patients who are not
      suitable for surgical resection and/or who refused surveillance or observation.
      MATERIAL AND METHOD: From January 2007 to August 2015, 164 treatments were
      performed on a total of 148 patients. We present the patients' clinical
      radiological characteristics, oncological and functional results in the short and
      medium term. RESULTS: The overall technical success rate was 97.5%, with a
      successful outcome in 1 session in 100% of the lesions<=3cm and 92% in lesions
      measuring 3-5cm. The mean tumour diameter in the patients for whom the treatment
      was ultimately successful was 2.7cm, while the mean diameter of these in the
      unsuccessful operations was 3.9cm (P<.05). There were no statistically
      significant differences in the serum creatinine levels and estimated glomerular
      filtration rates. CONCLUSIONS: Despite the low rate of positive renal biopsies in
      the series, ultrasound-guided percutaneous radiofrequency ablation for treating
      small renal lesions appears to be an effective and safe procedure with a minimum
      impact on renal function, an acceptable oncologic control in the short and medium
      term and a low rate of complications.

PMID- 28457498
TI  - Why Finance Should Care about Ecology.
AB  - Finance ignores ecosystems, which has resulted in a growing list of environmental
      and social problems. In this article, the importance of ecology for finance is
      assessed. We suggest The piece also suggests that the financial intermediation
      perspective can align finance and ecology for the benefit of society. This
      requires that financial institutions account for information about the impact of
      finance on the environment and vice versa, and that they are held accountable by
      their supervisors in this domain.

PMID- 28457497
TI  - [Linear ecchymosis of the back in an Asian patient].

PMID- 28457499
TI  - Milk fat globules and associated membranes: Colloidal properties and processing
      effects.
AB  - The composition and physical-chemical properties of the milk fat globule membrane
      (MFGM) is a subject that has gained increased interest in the field of food
      colloids, mainly because the nutritional and technological value of the MFGM. In
      fact, related changes in integrity and structure during milk processing pose a
      huge challenge as far as efforts directed to isolate the components of the fat
      globule membrane. MFGM characteristics and potential utilization are subjects of
      dissension. Thus, the effects of processing and the colloidal interactions that
      exist with other milk constituents need to be better understood in order to
      exploit milk fat and MFGM, their functionality as colloids as well as those of
      their components. These are the main subjects of this review, which also reports
      on the results of recent inquiries into MFGM structure and colloidal behavior.

PMID- 28457500
TI  - On the cohesion of fluids and their adhesion to solids: Young's equation at the
      atomic scale.
AB  - Using large-scale molecular dynamics simulations, we model a 9.2nm liquid bridge
      between two solid plates having a regular hexagonal lattice and analyse the
      forces acting at the various interfaces for a range of liquid-solid interactions.
      Our objective is to study the mechanical equilibrium of the system, especially
      that at the three-phase contact line. We confirm previous MD studies that have
      shown that the internal pressure inside the liquid is given precisely by the
      Laplace contribution and that the solid exerts a global force at the contact line
      in agreement with Young's equation, validating it down to the nanometre scale,
      which we quantify. In addition, we confirm that the force exerted by the liquid
      on the solid has the expected normal component equal to gammalvsintheta0, where
      gammalv is the surface tension of the liquid and theta0 is the equilibrium
      contact angle measured on the scale of the meniscus. Recent thermodynamic
      arguments predict that the tangential force exerted by the liquid on the solid
      should be equal to the work of adhesion expressed as Wa0=gammalv(1+costheta0).
      However, we find that this is true only when any layering of the liquid molecules
      close to liquid-solid interface is negligible. The force significantly exceeds
      this value when strong layering is present.

PMID- 28457501
TI  - Synthesis of hydroxyapatite for biomedical applications.
AB  - The current need for long lasting implants and bone substitutes characterized by
      biocompatibility, bioactivity and mechanical properties, without the immune
      rejection is a great challenge for scientists. These bone substitute structures
      should be prepared for individual patients with all details controlled on the
      micrometer level. Similarly, nontoxic, biocompatible targeted drug delivery
      systems which allow controlling the rate and time period of the drug delivery and
      simultaneously eliminating toxic and side effects on the healthy tissues, are of
      great interest. Extensive attempts have been made to develop a simple, efficient,
      and green method to form biofunctional scaffolds and implant coatings possessing
      the above mentioned significant biocompatibility, bioactivity and mechanical
      strength. Moreover, that could also serve as drug delivery systems.
      Hydroxyapatite (HA) which is a major mineral component of vertebrate bones and
      teeth is an excellent material for these purposes. In this literature review the
      biologically inspired scaffolds, bone substitutes, implants characterized by
      mechanical strength and biocompatibility, as well the drug delivery systems,
      based on hydroxyapatite are discussed.

PMID- 28457502
TI  - High-fidelity simulation: Who has the most impressive laboratory?

PMID- 28457503
TI  - Simultaneous quantification of batrachotoxin and epibatidine in plasma by ultra
      performance liquid chromatography/tandem mass spectrometry.
AB  - An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS)
      method was developed and validated for the simultaneous quantification of
      batrachotoxin and epibatidine in plasma. Plasma samples were pretreated by liquid
      liquid extraction with acetonitrile and methanol. The toxins were separated on a
      reversed phase C18-column (2.1mm*50mm, 1.7MUm) using a formic acid/acetonitrile
      gradient elution. Quantification was carried out by mass chromatography with each
      product ion referenced against midazolam-d4 as an internal standard (IS). The two
      toxins and the IS were separated within 2min. The calibration curves for the two
      toxins spiked into human plasma showed good linearities in the range from 2.5 to
      250ng/mL. The detection limits were estimated to be 0.5ng/mL for batrachotoxin
      and 1ng/mL for epibatidine with a signal-to-noise ratio of 3:1. Overall
      recoveries ranged from 69.6% to 98.2%, and no significant matrix effects were
      observed. The intra- and interday accuracies were 94.7-102.3%, and the precisions
      were 1.0-10.3%. This method was successfully applied for the quantification of
      batrachotoxin and epibatidine in rat plasma samples taken after intraperitoneal
      administration of the toxins. This is the first report to use UPLC-MS/MS to
      simultaneously quantify batrachotoxin and epibatidine in plasma samples.

PMID- 28457504
TI  - Analysis of postmortem changes in internal organs and gases using computed
      tomography data.
AB  - Postmortem computed tomography (PMCT) is a useful method to identify various
      causes of death and measure the volume of internal organs and gases. The purpose
      of this study was to investigate postmortem changes as measured by PMCT, and the
      relationship between the volume of organs and gases and postmortem interval
      (PMI). Forty-six cadavers (22 men, 24 women) were examined by CT before autopsy.
      The volumes of the lungs, intrahepatic gas, and intrarectal gas were measured by
      CT using a workstation. A stepwise regression analysis was used to establish a
      predictive equation to ascertain the measured volume using factors including sex,
      age, height, body mass index (BMI), body surface area (BSA), and PMI. For
      estimation of PMI, stepwise regression analysis was used. In the equations for
      each measured volume, height, diaphragmatic height, and BSA were adopted for the
      left lung; height and diaphragmatic height were adopted for the right lung; PMI
      was adopted for intrahepatic gas; and sex and PMI were adopted for intrarectal
      gas. In the PMI equations, left lung volume, intrahepatic gas, and intrarectal
      gas were adopted together with sex, weight, and BMI. Values of intrahepatic gas
      decreased with postmortem changes, while intrarectal gas increased. This may be
      useful in investigation of postmortem changes. It will be necessary to include
      other parts of the intestine and to analyze volume changes in gases from these
      parts after death.

PMID- 28457505
TI  - Evaluation of the medial clavicular epiphysis according to the Schmeling and
      Kellinghaus method in living individuals: A retrospective CT study.
AB  - The evaluation of the medial clavicular epiphysis via CT plays an important role
      in the determination of age, particularly the 19th and 22nd ages. Several authors
      have recommended the use of the Schmeling and Kellinghaus methods in conjunction
      in the evaluation of the medial clavicular epiphysis. The aim of this
      retrospective study was to evaluate thin section CT scan images of the medial
      clavicular epiphysis according to the Schmeling and Kellinghaus method, and to
      discuss the obtained data in the light of the literature. The thoracic CT scan
      images (0.6mm section thickness) of 601 patients (202 female and 399 male) aged
      between 10 and 35years obtained by 16-detector CT were evaluated by two
      examiners. The stage 2 was seen between 13 and 23years of age; stage 3 was seen
      between 16 and 27years of age. However, 100% of the female cases with stage 3c
      were ?18years of age, and 100% of the male cases with stage 3c were ?19years of
      age. Stage 4 was first observed at 20years of age in both sexes, and stage 5 was
      first observed at 25years of age in both sexes. We believe that stage 3c may be
      used, particularly in the determination 18-year age limit for both sexes. The
      outcomes of our study are consistent with those of our previous study and other
      studies in the literature, which is important for the confirmation of the
      reliability of the method.

PMID- 28457506
TI  - Calibration and parameter variation using a finite element model for death time
      estimation: The influence of the substrate.
AB  - The most established method for temperature based death time estimation is based
      on an empirical double exponential model. New physically based approaches using
      numerical simulation techniques are subject of current research. A major
      advantage of such models is the possibility to incorporate non-standard boundary
      conditions. The aim of this study was to investigate the influence of the
      substrate on the cooling rate of a body in the early postmortem phase. A finite
      element model was used for parameter variation in terms of different substrate
      materials. Simulation results showed a considerable influence of substrate
      material on the postmortem cooling rate of a body. From a thermodynamical point
      of view, comparability between measurements on a steel trolley and real cooling
      scenarios with common substrates like normal floors, asphalt or soil remains
      questionable. It could be shown that not only the type of substrate but also its
      composition can have a considerable influence on the postmortem body cooling
      rate.

PMID- 28457507
TI  - Age estimation by ossification of thyroid cartilage of Japanese males using
      Bayesian analysis of postmortem CT images.
AB  - Many studies have reported that the degree of thyroid cartilage ossification
      correlates with age. However, its use in forensics has been limited by individual
      variation, tissue fragility, and observer subjectivity. We examined a new method
      for age estimation from the degree of ossification of thyroid cartilage using
      postmortem computed tomography (CT) and Bayesian analysis. The scoring of CT
      density values, ossification rate, and morphological changes was performed in 131
      Japanese males (20-80years old), and an age estimation table was created and
      verified in 39 other Japanese males. We tried two types of prior probability; one
      was males undergoing postmortem CT imaging at our institute, and the other was
      the age composition of the male population in Japan. The differences in
      percentage in each age group were observed, especially in the ninth decade, but
      they were not large enough to change the result. Two decedents in their 30s and
      80s could not be assigned an age group. Likelihood might have had more
      significant influence than prior probability. Bayesian approach and new scoring
      system of thyroid cartilage ossification might be useful as an age estimation
      method. Although the low posterior probability in decedents the age ?70 remains a
      problem, the advantage of Bayesian estimation that it can sequentially update the
      age estimation table by factoring in exceptional data can solve this problem. In
      this study, accuracy of age estimation did not dramatically increase, however,
      Bayesian statistics might become a useful technique for examining any tissue
      samples subject to age-related calcification.

PMID- 28457508
TI  - An experimental study of postmortem decomposition of methomyl in blood.
AB  - Methomyl (S-methyl-1-N-[(methylcarbamoyl)oxy]thioacetimidate) is a carbamate
      pesticide. It has been noted that in some cases of methomyl poisoning, methomyl
      is either not detected or detected only in low concentrations in the blood of the
      victims. However, in such cases, methomyl is detected at higher concentrations in
      the vitreous humor than in the blood. This indicates that methomyl in the blood
      is possibly decomposed after death. However, the reasons for this phenomenon have
      been unclear. We have previously reported that methomyl is decomposed to dimethyl
      disulfide (DMDS) in the livers and kidneys of pigs but not in their blood. In
      addition, in the field of forensic toxicology, it is known that some compounds
      are decomposed or produced by internal bacteria in biological samples after
      death. This indicates that there is a possibility that methomyl in blood may be
      decomposed by bacteria after death. The aim of this study was therefore to
      investigate whether methomyl in blood is decomposed by bacteria isolated from
      human stool. Our findings demonstrated that methomyl was decomposed in human
      stool homogenates, resulting in the generation of DMDS. In addition, it was
      observed that three bacterial species isolated from the stool homogenates,
      Bacillus cereus, Pseudomonas aeruginosa, and Bacillus sp., showed methomyl
      decomposing activity. The results therefore indicated that one reason for the
      difficulty in detecting methomyl in postmortem blood from methomyl-poisoning
      victims is the decomposition of methomyl by internal bacteria such as B. cereus,
      P. aeruginosa, and Bacillus sp.

PMID- 28457509
TI  - Haplotypes from the SLC45A2 gene are associated with the presence of freckles and
      eye, hair and skin pigmentation in Brazil.
AB  - The Solute Carrier Family 45, Member 2 (SLC45A2) gene encodes the Membrane
      Associated Transporter Protein (MATP), which mediates melanin synthesis by
      tyrosinase trafficking and proton transportation to melanosomes. At least two
      SLC45A2 coding SNPs [E272K (rs26722) and L374F (rs16891982)] were reported
      influencing normal variation of human pigmentation. Here we aimed at evaluating
      the influence of haplotypes of 12 SNPs within SLC45A2 in the determination of
      eye, hair and skin pigmentation in a highly admixed population sample and
      comparing their frequencies with the ones found in data retrieved from the 1000
      Genomes Project. To achieve this goal, 12 SLC45A2 SNPs were evaluated in 288
      unrelated individuals from the Ribeirao Preto city area, Southeastern Brazil.
      SNPs were genotyped by PCR-RFLP or Allele-specific PCR, followed by
      polyacrylamide gel electrophoresis. Haplotypes of each individual were inferred
      by two independent computational methods, PHASE and Partition-Ligation
      Expectation-Maximization (PL-EM) algorithms, and 34 different haplotypes were
      identified. The hp9 haplotype was the most frequent (58.3%) and was associated
      with the presence of blond/red hair, pale skin, blue eyes and freckles. All
      haplotypes significantly associated with dark or light pigmentation features
      harbor the 374L and 374F alleles, respectively. These results emphasize the role
      played by haplotypes at SLC45A2 in the determination of pigmentation aspects of
      human populations and reinforce the relevance of SNP L374F in human pigmentation.

PMID- 28457510
TI  - Pattern recognition analysis of proton nuclear magnetic resonance spectra of
      postmortem cerebrospinal fluid from rats with drug-induced seizure or coma.
AB  - Cerebrospinal fluid (CSF) is routinely subjected to gross evaluation in
      postmortem investigations; however, its use in chemical evaluations has not been
      fully realized. Analysis of nuclear magnetic resonance (NMR) spectra with pattern
      recognition methods was applied to CSF samples. Rats were treated with
      pentylenetetrazol (PTZ) to induce seizure or pentobarbital (PB) to induce coma,
      and postmortem CSF was collected after CO2 gas euthanization. Pattern recognition
      analysis of the NMR data was performed on individual postmortem CSF samples. The
      aim of this study was to determine if pattern recognition analysis of NMR data
      could be used to classify the rats according to their drug treatment. The
      applicability of NMR data with pattern recognition analysis using postmortem CSF
      was also assessed. Partial Least Squares-Discriminant Analysis (PLS-DA) score
      plots indicated that the PTZ, PB, and NS (control) groups were clustered and
      clearly separated. PLS-DA correlation loading plots showed respective spectral
      and category variances of 41% and 42% for factor 1, and 17% and 27% for factor 2.
      Thus, factors 1 and 2 together described 58% (41%+17%) and 69% (42%+27%) of the
      variation, respectively. NMR study of postmortem CSF has the potential to be
      utilized as both a novel forensic neurochemistry method and in the clinical
      setting.

PMID- 28457511
TI  - Demirjian's stages and Cameriere's third molar maturity index to estimate legal
      adult age in Peruvian population.
AB  - OBJECTIVE: To compare the accuracy of Demirjian's stages (DS) and Cameriere's
      third molar maturity index cut-off value (I3M<0.08) to estimate the age of
      majority on panoramic radiographs (OPTs) from the dental clinic of the Scientific
      University of the South (UCSUR), Lima, Peru. METHODS: An observational cross
      sectional study was conducted on the sample of 208 digital panoramic radiographs
      of patients aged 14-22years examined during 2015 in UCSUR. The left lower third
      molars were analyzed using Adobe Photoshop(r) CS6. An effectiveness of specific
      DS and I3M<0.08 was evaluated by using accurate classification, sensitivity,
      specificity, positive (LR+) and negative (LR-) likelihood ratios and Bayes post
      test probability (p). RESULTS: Only G and H stages were practical for classify
      adults and minors in the tested sample, while I3M<0.08 showed the best
      performance in both sexes. For I3M<0.08, the accurate classification, sensitivity
      and specificity were 0.96, 0.96, 0.96 and 0.90, 0.84 and 0.95 in males and
      females, respectively. Values of LR+, LR- and p were 24.96, 0.04, 0.97 and 15.68,
      0.17, 0.95 in males and females, respectively. CONCLUSION: The specific cut-off
      value of third molar maturity index (I3M<0.08) showed to be more accurate in
      discriminating adults and minors in Peruvian sample when a test with high
      sensitivity and specificity is required.

PMID- 28457512
TI  - Sex prediction potential of hyoid metric measurements in Iranian adults.
AB  - OBJECTIVES: Human hyoid is sexually dimorphic and is useful for sexing unknown
      skeletal remains. We aimed to find sex prediction potential of three linear
      dimensions of hyoid bones obtained from a series of cadavers with Persian
      ethnicity. METHODS: This cross-sectional study was carried out in 2015 at
      Forensic Pathology Organization of Tehran, Iran. We directly measured three
      linear dimensions of a series of hyoid samples obtained from cadavers during
      their neck autopsy in a convenience method. These dimensions were width, length
      and distance between lesser horns of hyoid. Height and weight of cadavers were
      also documented. Cadavers were of Persian ethnicity and at least 25-year-old.
      Data were analyzed by SPSS16. Logistic Regression Model was applied to find
      independent sex predictor(s) of hyoid. Statistically significant level was
      considered <0.05. RESULTS: Hyoids of 349 adult cadavers (176 females and 173
      males) with mean+/-SD age of 39.91+/-8.13years were investigated. Male cadavers
      had significantly higher BMI values (p-value<0.001). Mean+/-SD for width, length
      and distance between lesser horns of hyoids were 34.45+/-4.70, 34.61+/-4.67 and
      22.71+/-2.80mm, respectively. All measured dimensions had greater mean values in
      males (all with p-values<0.001). After adjusting for BMI, length and distance
      between lesser horns of hyoid were independent predictors of sex with odd's ratio
      of 4.67 and 1.97, respectively. Combining these two measurements provided sex
      classification accuracy of 97.4%. CONCLUSION: Special metric hyoid indicators can
      help in accurate sexing of skeletal remnants of adult Iranians. Further studies
      will find the strongest sex predictors of hyoid bones among Persians.

PMID- 28457513
TI  - Fatal disseminated histoplasmosis presenting as FUO in an immunocompetent Italian
      host.
AB  - Histoplasmosis is a relatively rare infectious disease endemic to certain
      geographic areas such as East Africa, eastern and central United States, western
      Mexico, Central and South America. Disseminated histoplasmosis has been reported
      mainly in immunocompromised hosts and in AIDS patients. In this paper we report
      on a fatal case of undiagnosed disseminated histoplasmosis presenting as fever of
      unknown origin (FUO) in a 43-year-old Italian woman who, although splenectomized
      5years earlier due to a motor vehicle accident, was otherwise immunocompetent.
      This case report highlights the fact that, even in Europe, histoplasmosis is an
      emerging sporadic infection which needs be considered in the differential
      diagnosis of given clinical scenarios. The proposed case is of blatant forensic
      concern as it addresses the hypothesis of professional responsibility due to a
      missed diagnosis of histoplasmosis. A timely diagnosis, with appropriate
      therapies, could have prevented death. The role of the forensic pathologist is
      also crucial because the post-mortem diagnosis of histoplasmosis (never
      considered in the differential diagnosis during prior hospitalization) highlights
      the importance of a meticulous and thorough autopsy to elucidate the cause of
      death.

PMID- 28457514
TI  - Simple screening method for copy number variations associated with physical
      features.
AB  - Recent studies of copy number variations (CNVs) associated with physical
      features, such as body mass index, body height or bone length, have suggested
      that such CNVs could serve as markers in forensic cases involving unidentified
      individuals. However, the process of cataloging CNVs has been slow because of the
      cumbersome nature and low reliability of the procedures involved. Here we
      describe a simple quantitative real-time PCR (Q-PCR) method for screening of
      medicolegally useful CNVs, which does not require reference DNA with known copy
      number. The first step is to prepare a chimeric plasmid vector including one copy
      each of the single-copy gene-specific sequence as the internal standard, and the
      target CNV-specific sequence. To assess the validity of this new method, we
      analyzed CNVs in the LTBP1 and ETV6 gene regions, both of which are candidate
      CNVs associated with body height. The PCR efficiencies for the single-copy
      (reference) gene and the target CNV were similar, indicating that quantitation
      was reliable. Furthermore, simulated analysis of the LTBP1 CNV using mock samples
      prepared by mixing vectors in varying proportions showed that this analytical
      method allowed correct determination of the LTBP1 copy number. These results
      demonstrated that our simple method has considerable potential for screening of
      trait-related CNVs that would be useful for forensic casework.

PMID- 28457516
TI  - Relevance of hemolysis-induced tissue factor expression on monocytes in soft clot
      formation in alcohol-containing blood.
AB  - The fluidity of cadaveric blood is an important characteristic in the post-mortem
      examination of cases of asphyxial death. Although it is empirically known that
      soft blood clots are present in cadaveric blood containing alcohol, the
      relationship between such clots and blood alcohol is unclear. We addressed this
      issue through in vitro studies using blood collected from healthy volunteers.
      Assessment of global hemostasis by rotational thromboelastometry revealed that
      ethanol treatment enhanced the procoagulant activity of whole blood. However,
      ethanol inhibited epinephrine-induced platelet aggregation, whereas plasma levels
      of von Willebrand factor and the activity of coagulation factors VIII and IX were
      unaffected. In contrast, tissue factor (TF) activity was higher in plasma
      obtained from ethanol-treated whole blood than that in plasma from untreated
      blood. Ethanol induced hemolysis of red blood cells, and the consequent
      hemoglobin (Hb) release promoted de novo synthesis of TF in isolated monocytes,
      as determined by real-time reverse transcription PCR, western blotting, and flow
      cytometry. However, ethanol itself did not induce TF expression in monocytes.
      Given that TF activates the extrinsic coagulation pathway and amplifies
      hemostatic reactions, Hb-induced TF expression in monocytes might contribute to
      soft blood clot formation.

PMID- 28457515
TI  - Terminal restriction fragment length polymorphism profiling of bacterial flora
      derived from single human hair shafts can discriminate individuals.
AB  - Human hairs are the trace evidence most commonly encountered at many crime
      scenes. However, they have not been effectively utilized for actual criminal
      investigations because of the low accuracy of their morphological inspection, low
      detection rate of short tandem repeat (STR) typing, and the problem of
      heteroplasmy in mitochondrial DNA analysis. Here, we examined the possibility of
      individual discrimination by comparing profiles of bacterial flora on hair. We
      carried out the profiling of terminal restriction fragment length polymorphisms
      (T-RFLP) of the amplified bacterial 16S ribosomal RNA (rRNA) gene from hair
      samples. Compared with existing STR typing methods that use hair roots, this
      method using hair shafts allowed the detection of stable bacterial DNA. We
      successfully obtained the T-RFLP profile from single hair shafts of all
      volunteers tested. The profiles were specific to each individual, and multiple
      profiles obtained from the individual him/herself showed higher similarity than
      those from different individuals. These individual-specific profiles were stably
      obtained from samples from most volunteers, when collected again after 6months.
      Storage of the collected hair samples at -30 degrees C was effective for
      obtaining reproducible T-RF profiles. When unidentified hair samples collected in
      the laboratory were compared with a pre-constructed database, 17 of 22 hairs were
      assigned to a small group of people, including the corresponding individuals.
      These results show that T-RFLP analysis of bacterial flora on a hair shaft found
      at a crime scene could provide useful information for narrowing down a suspect.

PMID- 28457517
TI  - Direct high-pressure NMR observation of dipicolinic acid leaking from bacterial
      spore: A crucial step for thermal inactivation.
AB  - A bacterial spore protects itself with an unusually high concentration (~10% in
      dry weight of spore) of dipicolinic acid (DPA), the release of which is
      considered the crucial step for inactivating it under mild pressure and
      temperature conditions. However, the process of how the spore releases DPA in
      response to pressure remains obscure. Here we apply 1H high-resolution high
      pressure NMR spectroscopy, for the first time, to the spore suspension of
      Bacillus subtilis natto and monitor directly and in real-time the leaking process
      of DPA in response to pressure of 200MPa at 20 degrees C. We find that about one
      third of the total DPA leaks immediately upon applying pressure, but that the
      rest leaks slowly in hrs upon decreasing the pressure. Once DPA is fully released
      from the spore, the proteins of the spore become easily denatured at a mild
      temperature, e.g., 80 degrees C, much below the temperature commonly used to
      inactivate spores (121 degrees C). The success of the present experiment opens a
      new avenue for studying bacterial spores and cells at the molecular level in
      response to pressure, temperature and other perturbations.

PMID- 28457518
TI  - Systematic review of MRI findings in children with developmental delay or
      cognitive impairment.
AB  - AIM: To summarize the reported rates of magnetic resonance imaging (MRI)
      abnormalities in children with isolated global developmental delay (GDD) or
      intellectual disability (ID). METHOD: A literature search was conducted using
      electronic databases for studies reporting the rate of MRI abnormalities in
      children with clinically diagnosed ID or GDD and no other neurological signs,
      symptoms, or previously determined aetiology. All investigations with
      participants from birth to 18years were considered. Study quality was evaluated
      using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and
      Review Instrument (MAStARI) critical appraisal checklist items. RESULTS: Eighteen
      cross sectional, and 11 case-controlled studies adhered to inclusion criteria.
      Reported rates of abnormalities ranged from 0% to 98%. When all subjects with
      developmental delay from all papers were considered (n=2299) the total percentage
      found to have abnormalities was 38%. Abnormalities led to an etiological
      diagnosis for delay in 7.9% of cases. INTERPRETATION: Definitions of
      abnormalities varied widely between studies, and drastically different rates of
      abnormalities are reported. Currently available evidence is not of sufficient
      quality to make firm recommendations on the use of neuroimaging in ID or GDD but
      MRI should be considered for children that do not have a diagnosis after thorough
      clinical evaluation.

PMID- 28457519
TI  - Commentaries: More Than Just a New Section in Actas.

PMID- 28457520
TI  - History of neurology: A desirable past?

PMID- 28457521
TI  - Image processing can cause some malignant soft-tissue lesions to be missed in
      digital mammography images.
AB  - AIM: To investigate the effect of image processing on cancer detection in
      mammography. METHODS AND MATERIALS: An observer study was performed using 349
      digital mammography images of women with normal breasts, calcification clusters,
      or soft-tissue lesions including 191 subtle cancers. Images underwent two types
      of processing: FlavourA (standard) and FlavourB (added enhancement). Six
      observers located features in the breast they suspected to be cancerous (4,188
      observations). Data were analysed using jackknife alternative free-response
      receiver operating characteristic (JAFROC) analysis. Characteristics of the
      cancers detected with each image processing type were investigated. RESULTS: For
      calcifications, the JAFROC figure of merit (FOM) was equal to 0.86 for both types
      of image processing. For soft-tissue lesions, the JAFROC FOM were better for
      FlavourA (0.81) than FlavourB (0.78); this difference was significant (p=0.001).
      Using FlavourA a greater number of cancers of all grades and sizes were detected
      than with FlavourB. FlavourA improved soft-tissue lesion detection in denser
      breasts (p=0.04 when volumetric density was over 7.5%) CONCLUSIONS: The detection
      of malignant soft-tissue lesions (which were primarily invasive) was
      significantly better with FlavourA than FlavourB image processing. This is
      despite FlavourB having a higher contrast appearance often preferred by
      radiologists. It is important that clinical choice of image processing is based
      on objective measures.

PMID- 28457523
TI  - Underdiagnosis of Mild Congenital Anorectal Malformations.
AB  - OBJECTIVE: To determine whether the frequency and severity of congenital
      anorectal malformations (CARMs) differs by sex. STUDY DESIGN: We included 129
      patients (0-319 weeks old) diagnosed with CARMs, who had been referred to our
      Department of Pediatric Surgery between 2004 and 2013. Rectoperineal and
      rectovestibular fistulas were classified as mild CARMs, all others as severe. If
      a patient was diagnosed with CARM within 48 hours after birth, this was
      considered an early diagnosis, all others as late. RESULTS: Seventy-five (58%)
      girls and 54 (42%) boys were diagnosed with different forms of CARM. More
      patients had mild rather than severe forms of CARM (67% and 33%, respectively, P
      <.001). We found that 89% of girls had a mild form of CARM, whereas 65% of boys
      had severe forms (P <.001). All severe forms were diagnosed early, whereas 54%
      mild forms were diagnosed early and 46% were diagnosed late. CONCLUSIONS: Girls
      more often have mild forms of CARM, whereas boys more often have severe forms.
      Overall, the distribution across the sexes is equal. Because chronic constipation
      can be the only symptom of mild CARMs, it often requires more time to diagnose
      than severe forms. Many women are, therefore, diagnosed with CARMs at an older
      age, or they may go undiagnosed altogether. Subsequently, these women have a
      greater risk of full rupture during vaginal delivery.

PMID- 28457522
TI  - Lung Transplantation for FLNA-Associated Progressive Lung Disease.
AB  - OBJECTIVE: To describe a series of patients with pathogenic variants in FLNA and
      progressive lung disease necessitating lung transplantation. STUDY DESIGN: We
      conducted a retrospective chart review of 6 female infants with heterozygous
      presumed loss-of-function pathogenic variants in FLNA whose initial presentation
      was early and progressive respiratory failure. RESULTS: Each patient received
      lung transplantation at an average age of 11 months (range, 5-15 months). All
      patients had pulmonary arterial hypertension and chronic respiratory failure
      requiring tracheostomy and escalating levels of ventilator support before
      transplantation. All 6 patients survived initial lung transplantation; however, 1
      patient died after a subsequent heart-lung transplant. The remaining 5 patients
      are living unrestricted lives on chronic immunosuppression at most recent follow
      up (range, 19 months to 11.3 years post-transplantation). However, in all
      patients, severe ascending aortic dilation has been observed with aortic
      regurgitation. CONCLUSIONS: Respiratory failure secondary to progressive
      obstructive lung disease during infancy may be the presenting phenotype of FLNA
      associated periventricular nodular heterotopia. We describe a cohort of patients
      with progressive respiratory failure related to a pathogenic variant in FLNA and
      present lung transplantation as a viable therapeutic option for this group of
      patients.

PMID- 28457524
TI  - Early Adiposity Rebound and Premature Adrenarche.
AB  - OBJECTIVES: To examine differences in the growth pattern and the age at adiposity
      rebound (AR) between children with premature adrenarche (PA) and their healthy
      peers (controls). STUDY DESIGN: In this cross-sectional study of 82 prepubertal
      children with PA and 63 controls, the main outcome measures were height and body
      mass index SDS progression, from birth to presentation at the clinic, baseline
      biochemical and hormonal evaluation, bone age determination, and age at AR.
      RESULTS: Children with PA were significantly taller and more adipose than
      controls from the first years of life. 33% of children with PA presented the
      growth pattern of constitutional advancement of growth (ie, early growth
      acceleration) vs 19% of controls (P = .045). Children with PA had an earlier AR
      compared with controls; mean age at AR in girls with PA was 3.73 (1.03) years vs
      4.93 (1.36) years for control girls (P = .001) and in boys with PA was 3.45
      (0.73) vs 5.10 (1.50) years in control boys (P = .048). Both obese and nonobese
      girls with PA were taller and had earlier age at AR compared with nonobese
      controls. CONCLUSIONS: Early AR and constitutional advancement of growth may be
      triggering factors for adrenal androgen production and PA.

PMID- 28457525
TI  - Retrospective Study Evaluating Treatment Decisions and Outcomes of Childhood
      Uveitis Not Associated with Juvenile Idiopathic Arthritis.
AB  - OBJECTIVE: To evaluate treatment, ocular complications and outcomes of children
      with pediatric uveitis not associated with juvenile idiopathic arthritis. STUDY
      DESIGN: This was a retrospective chart review of pediatric uveitis in children
      under 16 years of age, recruited from the pediatric rheumatology department at
      Bicetre Hospital from 2005 to 2015. Patients with juvenile idiopathic arthritis
      associated and infectious uveitis were excluded. We used the Standardization of
      Uveitis Nomenclature Working Group to classify uveitis, disease activity, and
      treatment end points. RESULTS: We enrolled 56 patients and 102 affected eyes. The
      mean age at diagnosis was 10 +/- 3.5 years (range 3-15), and the mean follow-up
      4.2 +/- 3.3 years (1-15). The main diagnoses were idiopathic (55%), Behcet
      disease (15%), and sarcoidosis (5%). The main localization was panuveitis in 44
      of 102 eyes (43%). Corticosteroid sparing treatment was needed in 62 of 102 eyes
      (60%). Second-line therapies included methotrexate and azathioprine, and the
      third-line therapy was a biologic agent, mainly infliximab, in 33 of 102 eyes
      (32%). Infliximab achieved uveitis inactivity in 14 of 18 eyes (80%), in all
      etiologies. Severe complications were present in 68 of 102 eyes (67%). The most
      common were synechiae 33% of eyes, cataract (20%), and macular edema (25%). Of
      these, 37% were present at diagnosis. Remission was achieved in 22 of 102 eyes
      (21%). CONCLUSIONS: Conventional therapies were insufficient to treat many of the
      cases of posterior or panuveitis. This study underlines the need for earlier and
      more aggressive treatment and antitumor necrosis factor-alpha therapy was rapidly
      efficient in most cases of refractory uveitis.

PMID- 28457526
TI  - Delayed Diagnoses in Children with Constipation: Multicenter Retrospective Cohort
      Study.
AB  - OBJECTIVE: The use of abdominal radiographs contributes to increased healthcare
      costs, radiation exposure, and potentially to misdiagnoses. We evaluated the
      association between abdominal radiograph performance and emergency department
      (ED) revisits with important alternate diagnosis among children with
      constipation. STUDY DESIGN: Retrospective cohort study of children aged <18 years
      diagnosed with constipation at one of 23 EDs from 2004 to 2015. The primary
      exposure was abdominal radiograph performance. The primary outcome was a 3-day ED
      revisit with a clinically important alternate diagnosis. RAND/University of
      California, Los Angeles methodology was used to define whether the revisit was
      related to the index visit and due to a clinically important condition other than
      constipation. Regression analysis was performed to identify exposures
      independently related to the primary outcome. RESULTS: A total of 65.7% (185
      439/282 225) of children with constipation had an index ED visit abdominal
      radiograph performed. Three-day revisits occurred in 3.7% (10 566/282 225) of
      children, and 0.28% (784/282 225) returned with a clinically important alternate
      related diagnosis. Appendicitis was the most common such revisit, accounting for
      34.1% of all 3-day clinically important related revisits. Children who had an
      abdominal radiograph performed were more likely to have a 3-day revisit with a
      clinically important alternate related diagnosis (0.33% vs 0.17%; difference
      0.17%; 95% CI 0.13-0.20). Following adjustment for covariates, abdominal
      radiograph performance was associated with a 3-day revisit with a clinically
      important alternate diagnosis (aOR: 1.39; 95% CI 1.15-1.67). Additional
      characteristics associated with the primary outcome included narcotic (aOR: 2.63)
      and antiemetic (aOR: 2.35) administration and underlying comorbidities (aOR:
      2.52). CONCLUSIONS: Among children diagnosed with constipation, abdominal
      radiograph performance is associated with an increased risk of a revisit with a
      clinically important alternate related diagnosis.

PMID- 28457527
TI  - Persistent Enteropathy in a Toddler with a Novel FOXP3 Mutation and Normal FOXP3
      Protein Expression.
AB  - Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome
      is caused by mutations in the FOXP3 gene. Patients usually present with a
      clinical triad of intractable diarrhea, diabetes, and eczema. In this patient,
      FOXP3 protein expression was normal, but FOXP3 Sanger sequencing confirmed the
      clinical suspicion of IPEX by detecting a previously unreported missense variant.
      Early recognition of IPEX is important, because hematopoietic stem cell
      transplantation can be curative.

PMID- 28457528
TI  - Disease associations with isolated elevations of each of the four IgG subclasses.
AB  - PURPOSE: Immunoglobulin G4-related disease (IgG4-RD) is a relatively newly
      defined disease entity that refers to a group of immune-mediated disorders that
      have certain histopathologic, serologic, and clinical features in common. IgG4-RD
      is often associated with elevated serum IgG4. The discovery of IgG4-RD highlights
      the scarcity of literature examining elevations in other IgG subclasses and their
      potential associations to disease. In this retrospective chart review study, we
      aim to address that gap, by exploring disease associations in patients with
      isolated IgG subclass elevations. METHODS: We identified 552 patients with an
      isolated elevation of one of the IgG subclasses, and performed a systematic chart
      review to identify the diagnoses of those patients. We examined the distribution
      of diagnoses, using the Fisher's exact test to determine if a diagnosis was
      significantly associated with an isolated elevation in one of the subclasses.
      RESULTS: Autoimmune pancreatitis, aspirin-exacerbated respiratory disease (AERD),
      nasal polyps, eosinophilia, and celiac disease were significantly associated with
      an isolated elevation in IgG4. Hepatitis C and monoclonal gammopathy were
      significantly associated with isolated elevations in IgG1. Rheumatoid arthritis
      (RA) was associated with both an isolated elevation in IgG1 and IgG3.
      Hypothyroidism and irritable bowel syndrome (IBS) were significantly associated
      with isolated elevations in IgG2. CONCLUSION: These results confirmed some
      established associations between autoimmune pancreatitis, AERD, nasal polyps, and
      eosinophilia and elevated serum IgG4, and between monoclonal gammopathy and
      hepatitis C with elevated serum IgG1. It uncovered novel associations between RA
      and elevated IgG1 and IgG3, hypothyroidism and IBS and elevated IgG2, and between
      celiac disease and elevated IgG4.

PMID- 28457529
TI  - Fructose malabsorption in people with and without gout: A case-control study.
AB  - BACKGROUND: Higher fructose intake has been associated with hyperuricaemia and
      gout. Some individuals malabsorb fructose in the small intestine. The aims of
      this study were to determine the rate of fructose malabsorption and the effects
      of gout and fructose malabsorption on serum urate in people with and without
      gout. METHODS: A total of 100 people with gout (cases) were age and gender
      matched with one control without gout. After a low fructose diet, fructose
      malabsorption was measured using a hydrogen and methane breath test with a 35g
      fructose load. In a subgroup of 35 cases and 35 controls, serum urate response to
      the fructose load over 240 minutes was measured. RESULTS: There was no
      significant difference in the rate of fructose malabsorption between cases and
      controls (48% vs. 52%; p = 0.67). Cases had a significantly lower mean (SEM)
      serum urate cumulative incremental concentration from baseline-240 minutes (iAUC0
      240) compared to controls 0.97 (0.56) vs. 4.78 (0.55); p < 0.001. Cmax was
      significantly lower in cases compared to controls [0.38 (0.003) vs. 0.40 (0.003);
      p < 0.001]. 95% of cases were receiving allopurinol. There was no significant
      difference between iAUC0-240 or Cmax for malabsorbers compared to normal
      absorbers irrespective of case-control status. The mean (SEM) increase in serum
      urate between baseline and 30 minutes was 0.04 (0.004)mmol/l in the controls
      compared to 0.009 (0.002) in the cases (p < 0.001). CONCLUSION: The rates of
      fructose malabsorption are similar in people with and without gout. Allopurinol
      inhibits the increase in serum urate induced by a fructose load suggesting that
      people with gout receiving allopurinol may not need to restrict dietary intake of
      fructose.

PMID- 28457530
TI  - Long-term outcomes of coronary artery bypass grafting versus percutaneous
      coronary intervention for Takayasu arteritis patients with coronary artery
      involvement.
AB  - OBJECTIVE: Coronary artery involvement significantly increases mortality of
      patients with Takayasu arteritis (TA); however, the optimal revascularization
      strategy for this condition has not been established. We aimed to compare the
      long-term outcomes of TA patients with coronary artery involvement treated with
      coronary artery bypass grafting (CABG) and percutaneous coronary intervention
      with stenting (PCI). METHODS: Data from 46 TA patients with coronary artery
      involvement were analyzed according to their revascularization strategies. The
      resulting events included myocardial infarction, repeated revascularization,
      cardiac death, and the major adverse cardiac events (MACE), which is a
      combination of the former events. RESULTS: The risk of MACE was significantly
      higher in the PCI group than in the CABG group during a median of 41.0 months
      follow-up (P < 0.001), especially in those who underwent revascularization at the
      active stage of TA (P = 0.001), whereas no difference was found between PCI and
      CABG groups in patients who underwent revascularization at the stable stage of TA
      (P = 0.138). The incidence of MACE was higher in TA patients at the active stage
      than those at the stable stage in all patients (P < 0.001). For patients at the
      active stage, the risk of MACE was significantly lower in patients with than
      those without usage of prednisone (P = 0.028); while no difference was found
      between patients who were stable not requiring prednisone and patients who were
      stable on prednisone (P = 0.525). CONCLUSION: With regard to MACE, CABG is
      superior to PCI despite medical therapy in TA patients with coronary artery
      involvement. In TA patients at the stable stage, PCI is similar with CABG in
      prognosis. For patients at the active stage, if emergency revascularization is
      necessary, CABG is ideal; if not, receiving medical therapy until disease
      remission and then undergoing PCI may be an alternative choice of CABG.

PMID- 28457531
TI  - Spatial development of gingival fibroblasts and dental pulp cells: Effect of
      extracellular matrix.
AB  - Cells sensing changes in their microenvironmental stiffness and composition alter
      their responses, accordingly. This study determines whether gingival fibroblasts
      (GFs) and dental pulp mesenchymal stem cells (DPMSCs) support the formation of
      continuous layers in vitro by mimicking the stiffness and protein composition of
      their native extracellular matrix (ECM). Immortalized cells were incubated with
      (i) 0-100% Matrigel-ECM (M-ECM) for 7-28d, and with (ii) collagen and fibrin
      matrices for 14d. Cultures were analyzed by phase-contrast, fluorescence and
      confocal microscopies. The diameters and surface areas were measured via ImageJ.
      Self-renewal markers were detected by RT-PCR and immunocytochemistry assays. GFs
      and DPMSCs developed spheroids interconnected by elongated cell bundles or
      layers, respectively, expressing the self-renewal markers. Increased matrix
      stiffness resulted in spheroids replacement by the interconnecting cells/layers.
      Both cells required 100% M-ECM to reduce their spheroid diameter. However, it
      reduced the surface area of the interconnecting layers. Those differences led to
      extended, spindle-shaped GFs vs. compact, ring-shaped DPMSCs constructs. Collagen
      and fibrin matrices developed continuous layers of tightly connected cells vs.
      distinctive scattered cell aggregates, respectively. The ability of GFs and
      DPMSCs to create tissue-like multicellular layers at various matrix conditions
      may be imprinted by cells' adaptation to mechanical forces and composition in
      vivo.

PMID- 28457532
TI  - Usefulness of multidetector computed tomography before and after pulmonary vein
      isolation.
AB  - OBJECTIVE: To analyze the usefulness of multidetector computed tomography (MDCT)
      in the preprocedural evaluation and follow-up of patients undergoing
      radiofrequency ablation of pulmonary veins and the impact of the MDCT findings on
      the approach to treatment. METHOD: We retrospectively analyzed 92 consecutive
      MDCT studies done in 80 patients between January 2011 and June 2013; 70 (76%)
      studies were done before a first ablation procedure and 22 (24%) were done in
      patients who had undergone an ablation procedure. RESULTS: Findings were useful
      in 34% of the patients who underwent MDCT before the first ablation procedure and
      in 68% of the studies done after a procedure. The incidence of stroke associated
      with the ablation procedure was 3%, similar to the incidence recorded in our
      center before we started to use MDCT to evaluate the anatomy of the left atrium.
      All symptomatic patients had some pulmonary vein stenosis, and 80% had
      significant stenosis. Furthermore, the stenoses progressed very rapidly;
      treatment with balloon angioplasty was associated with early restenosis. Stenting
      was an alternative in cases of failed angioplasty. CONCLUSION: In the
      preprocedural evaluation and postprocedural follow-up of patients undergoing
      pulmonary vein isolation, MDCT is useful for guiding treatment and detecting
      complications.

PMID- 28457533
TI  - Schwannoma of the breast: an unexpected diagnosis by magnetic resonance.
AB  - Schwannomas consist of benign tumors that arise from the nerves, however, they
      are not frequent in the breast. Our search criteria only found 28 cases described
      in Literature. We show the case about a 63 years old woman who underwent a breast
      magnetic resonance (MR) because of high risk for breast cancer, in which a
      lession on her left breast was found. Not only MR features seemed to be benign,
      but ultrasound and mamography features, too. The diagnosis of schwannoma was
      confirmed by ultrasound-guided biopsy. Findings in conventional radiology were
      correlated with those described in the reviewed literature. In our opinion, this
      case results valuable due to the inicial diagnosis by MR, which is not an imaging
      proof for bening tumors, innitially. According to the revised bibliography these
      features are pretty funny, as mamography and ultrasound, with histological
      findings, are the clues for the usual diagnosis.

PMID- 28457535
TI  - Mitochondrial transplantation: Another miracle of molecular medicine?

PMID- 28457536
TI  - Pre- versus postoperative chemoradiotherapy for locally advanced esophageal
      squamous cell carcinoma.
AB  - OBJECTIVES: Although preoperative chemoradiation followed by surgery has been
      recognized as an efficient strategy for esophageal cancer treatments, several
      studies demonstrate survival benefits of postoperative chemoradiation for those
      undergoing upfront resection. The optimal sequence of surgery and chemoradiation
      remains unclear. METHODS: Data of 1647 patients with clinical stage II/III
      esophageal squamous cell carcinoma (ESCC), including 1245 receiving preoperative
      chemoradiation followed by esophagectomy (pre-OP CRT group) and 402 receiving
      primary esophagectomy followed postoperative chemoradiation (post-OP CRT group),
      were obtained from a nationwide database. Propensity score matching identified
      286 well-balanced pairs for outcome comparison. RESULTS: In matched patients, the
      3-year overall survival (OS) rates/median survival were not significantly
      different between the 2 groups (44.0% 3-year OS/26.0 months; 95% confidence
      interval [CI], 18.9-89 38.0 months) in the pre-OP CRT group, versus 37.9% 3-year
      OS/23.5 months (95% CI, 18.5-29.9 months) in the post-OP CRT group, P = .3152).
      The 3-year disease-free survival rates (DFS)/median survival after surgery were
      38.7% 3-year DFS/16.7 months (95% CI, 11.9-29.6 months) in the pre-OP CRT group,
      compared with 30.2% 3-year DFS/10.4 months (95% CI, 7.6-14.0 months) in the post
      OP CRT group (P = .0674). In patients who had complete resection, the freedom
      from recurrence rate at 1 year after surgery was 74.8% and 67.6% in pre-OP CRT
      and post-OP CRT groups, respectively (P = .2696). In the multivariable analysis,
      treatment modality (pre- or post-OP CRT) was not a significant factor for OS (P =
      .258) or disease-free survival (P = .521). CONCLUSIONS: Similar outcome can be
      achieved with postoperative chemoradiotherapy compared with preoperative
      chemoradiotherapy in patients with locally advanced ESCC. There is little
      difference between these 2 strategies.

PMID- 28457534
TI  - Choice of the specialty of diagnostic radiology by results of the competitive
      examination to assign residency positions from 2006 to 2015.
AB  - OBJECTIVE: To analyze the profile of residency candidates choosing the specialty
      of diagnostic radiology in function of variables related to the positions
      available in different years. MATERIAL AND METHODS: We compiled the data
      published on the Spanish Ministry of Health's website during the acts celebrated
      to allow residency candidates to choose positions based on the results of the
      competitive examinations held from 2006 to 2015, comparing the specialty of
      diagnostic radiology with the other specialties available in terms of positions
      available, net questions, sex, nationality, and order of choice of the position.
      RESULTS: The specialty of diagnostic radiology occupied the 16th position in the
      ranking of specialties according to the median number of order in the choice for
      each of the positions offered in the years studied. The first diagnostic
      radiology residency position was usually assigned after 75 candidates had chosen
      other specialties, and the last position was usually assigned after 3700 to 4100
      candidates had chosen their positions. During the period studied, of those who
      chose diagnostic radiology 58% were women and 76% were Spanish nationality.
      Candidates preferred hospitals in the Autonomous Community of Madrid, and the
      hospital chosen with the lowest median position (highest score on the competitive
      examination) was the Hospital Clinic de Barcelona. CONCLUSIONS: Diagnostic
      radiology is chosen by candidates with good positioning in the ranking according
      to official examination results, is less likely than other specialties to be
      chosen by women, and is chosen mostly by Spanish physicians. Candidates prefer
      large hospitals in provincial capitals.

PMID- 28457537
TI  - The long view.

PMID- 28457538
TI  - Data, not dogma, for ischemic mitral regurgitation.

PMID- 28457539
TI  - Echocardiographic visualization and quantification of mitral complex during
      mitral repair for severe functional mitral regurgitation.

PMID- 28457540
TI  - Lymph node metastases in thymic tumors: The more we know, the less we know.

PMID- 28457541
TI  - Living on the edge: Does cut mean cure for pulmonary mucosa-associated lymphoid
      tissue?

PMID- 28457542
TI  - Aortic grafts: Is math the right angle?

PMID- 28457543
TI  - Prognostic impact of stathmin 1 expression in patients with lung adenocarcinoma.
AB  - OBJECTIVE: Stathmin 1 is a major cytosolic phosphoprotein that regulates
      microtubule dynamics and is associated with malignant phenotypes in various
      cancers, including non-small cell lung cancer. We aimed to determine differences
      in overall survival and disease-free proportion in patients with lung
      adenocarcinoma stratified by stathmin 1 tumor expression. METHODS: With the use
      of immunohistochemistry, stathmin 1 expression was determined in resection
      specimens from 303 patients with adenocarcinoma. Associations between stathmin 1
      protein expression and overall and disease-free proportion were assessed (Kaplan
      Meier survival curves compared with log-rank statistics). Cox proportional
      hazards regression determined the hazard for death stratified by stathmin 1,
      adjusting for clinicopathologic characteristics. RESULTS: During follow-up, 74
      (24.4%) recurrences and 73 (24.1%) all-cause deaths were recorded. Expressed in
      53.8% of adenocarcinoma cases, overall survival and disease-free proportion were
      significantly worse in stathmin 1-positive patients (log-rank P < .001 and P <
      .001, respectively). When adjusted for clinical and pathologic factors, stathmin
      1 expression was an independent prognostic variable for both overall survival
      (hazard ratio, 2.21; 95% confidence interval, 1.28-3.80) and disease-free
      proportion (hazard ratio, 2.02; 95% confidence interval, 1.13-3.63) and for
      disease-free proportion even in the subset of patients with stage I (hazard
      ratio, 2.79; 95% confidence interval, 1.07-7.27). There was no significant
      difference between the stathmin 1-positive patients with stage IA and patients
      with stage IB in overall survival (P = .975) and disease-free proportion (P =
      .490), respectively. CONCLUSIONS: Stathmin 1 expression was an independent
      prognostic factor for adenocarcinoma, even when restricted to patients with early
      stage cancer.

PMID- 28457544
TI  - Treatment outcomes in patients with extranodal marginal zone B-cell lymphoma of
      the lung.
AB  - OBJECTIVES: To evaluate clinical presentations, treatment modalities, and
      outcomes of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma by stage
      strata. METHODS: We retrospectively reviewed 51 patients diagnosed with pulmonary
      MALT lymphoma between January 2003 and December 2015. To compare treatment
      modalities and outcomes, we stratified the patients into low-stage (IE/IIE) and
      high-stage (IIIE/IVE) groups using modified Ann Arbor staging. Progression-free
      survival was estimated using Kaplan-Meier curves, and differences were compared
      using the log-rank test. A hazard ratio of progression by stage strata, adjusted
      for other clinical variables, was determined using a Cox adjusted proportional
      hazards model. RESULTS: The majority of patients had stage IE disease (76.5%; 39
      of 51). With advancing stage, patients were more likely to have respiratory and B
      symptoms and higher International Prognostic Index scores. The most common
      treatment modality was surgical resection in low-stage patients (33 of 43) and
      chemotherapy in high-stage patients (7 of 8). At a median follow-up of 40.7
      months, progression-free survival was longer for low-stage patients (median, 40.7
      months vs 24.9 months; P < .001), and high-stage patients were 9.2 times more
      likely to progress (hazard ratio, 9.24; 95% confidence interval, 1.93-44.36).
      Among 30 patients with surgically resected stage IE disease, 8 with central
      lesions were treated via lobectomy and 22 with peripheral lesions were treated
      via lobectomy (n = 8) or limited resection (n = 14). One of these patients, with
      a central lesion, experienced disease recurrence. CONCLUSIONS: Our findings
      suggest that the clinical course of low-stage pulmonary MALT lymphoma, for which
      the mainstay of treatment is surgical resection, might be indolent.

PMID- 28457545
TI  - Change is the only constant.

PMID- 28457546
TI  - Comparison of 4 label-based immunochromatographic assays for the detection of
      Escherichia coli O157:H7 in milk.
AB  - Immunochromatographic assays (ICA) are widely used to detect pathogens. In this
      study, we used traditional gold nanoparticles (GNP), quantum dots (QD),
      fluorescent nanoparticles (FNP), and europium (Eu) (III) chelate nanoparticles
      (EuNP) as ICA labels. We first compared the ability of the 4 ICA test strips to
      quantitatively detect Escherichia coli O157:H7 in milk. We then optimized various
      parameters influencing the ICA. The sensitivity to E. coli O157:H7 of the GNP
      ICA, QD-ICA, FNP-ICA, and EuNP-ICA was 2.5 * 104, 5 * 103, 1.0 * 103, and 5.0 *
      102 cfu mL-1, respectively. The EuNP-ICA exhibited the highest sensitivity. The
      amounts of monoclonal antibodies (mAb) per GNP-ICA, QD-ICA, FNP-ICA, and EuNP-ICA
      test strip were 0.16, 0.37, 0.04, and 0.10 MUg, respectively. The corresponding
      coefficients of variation were 7.4 to 15.8%, 10.4 to 18.6%, 2.7 to 7.8%, and 6.9
      to 10.5%, respectively. The FNP-ICA required the least mAb per test strip and had
      the best coefficient of variation. The linear ranges of GNP-ICA, QD-ICA, FNP-ICA,
      and EuNP-ICA were 1.0 * 104 to 1.0 * 106, 2.5 * 103 to 1.0 * 106, 2.5 * 102 to
      2.5 * 105, and 2.5 * 102 to 2.5 * 105 cfu mL-1, respectively. The FNP-ICA and
      EuNP-ICA had wider linear ranges than GNP-ICA and QD-ICA. Additionally, the FNP
      ICA and EuNP-ICA showed better tolerance than GNP-ICA and QD-ICA in the milk
      samples. The FNP-ICA and EuNP-ICA showed remarkable potential for detection of
      pathogens in milk.

PMID- 28457548
TI  - Molecular characterization and antibiotic resistance of Staphylococcus spp.
      isolated from cheese processing plants.
AB  - The aim of this research paper was to characterize coagulase-positive and
      coagulase-negative staphylococci from raw milk, Minas cheese, and production
      lines of Minas cheese processing. One hundred isolates from 3 different cheese
      producers were characterized using molecular approaches, such as PCR, molecular
      typing, and DNA sequencing. Staphylococcus aureus (88% of the isolates) was the
      most abundant followed by Staphylococcus epidermidis, Staphylococcus hyicus, and
      Staphylococcus warneri. Among the 22 enterotoxin genes tested, the most frequent
      was seh (62% of the isolates), followed by selx and ser. Hemolysin genes were
      widely distributed across isolates, and Panton-Valentine leukocidin and toxic
      shock syndrome toxin genes were also identified. Methicillin-resistant S. aureus
      were staphylococcal cassette chromosome mec III, IVa, IVd, and others
      nontypeable. In the phenotypic antibiotic resistance, multiresistant isolates
      were detected and resistance to penicillin was the most observed. Using spa
      typing, we identified several types and described a new one, t14969, isolated
      from cheese. These findings suggest that antibiotic resistance and potentially
      virulent strains from different sources can be found in the Brazilian dairy
      processing environment. Further research should be conducted with collaboration
      from regulatory agencies to develop programs of prevention of virulent and
      resistant strain dissemination in dairy products and the processing environment.

PMID- 28457547
TI  - The effect of dry period length and postpartum level of concentrate on milk
      production, energy balance, and plasma metabolites of dairy cows across the dry
      period and in early lactation.
AB  - Shortening or omitting the dry period (DP) improves energy balance (EB) in early
      lactation because of a reduction in milk yield. Lower milk yield results in lower
      energy demands and requires less energy intake. The aim of this study was to
      evaluate the effects of DP length and concentrate level postpartum on milk yield,
      feed intake, EB, and plasma metabolites between wk -4 and 7 relative to calving
      of cows of second parity or higher. Holstein-Friesian dairy cows (n = 123) were
      assigned randomly to 1 of 2 DP lengths: 0-d DP (n = 81) or 30-d DP (n = 42).
      Prepartum, cows with a 0-d DP received a lactation ration based on grass silage
      and corn silage (6.4 MJ of net energy for lactation/kg of dry matter). Cows with
      a 30-d DP received a dry cow ration based on grass silage, corn silage, and straw
      (5.4 MJ of net energy for lactation/kg of dry matter). Postpartum, all cows
      received the same basal lactation ration as provided to lactating cows prepartum.
      Cows with a 0-d DP were fed a low level of concentrate up to 6.7 kg/d based on
      the requirement for their expected milk yield (0-d DP-L; n = 40) or the standard
      level of concentrate up to 8.5 kg/d (0-d DP-S; n = 41), which was equal to the
      concentrate level for cows with a 30-d DP (30-d DP-S; n = 42) based on
      requirements for their expected milk yield. Prepartum dry matter intake,
      concentrate intake, basal ration intake, energy intake, plasma beta
      hydroxybutyrate (BHB), and insulin concentrations were greater and plasma free
      fatty acids (FFA) and glucose concentrations were lower, but EB was not different
      in cows with a 0-d DP compared with cows with a 30-d DP. During wk 1 to 3
      postpartum, milk fat yield and plasma BHB concentration were lower and dry matter
      intake and concentrate intake were greater in cows with a 0-d DP compared with
      cows with a 30-d DP. During wk 4 to 7 postpartum, fat- and protein-corrected milk
      (FPCM), lactose content, and lactose and fat yield were lower in 0-d DP-L or 0-d
      DP-S cows compared with 30-d DP-S cows. Basal ration intake, EB, body weight,
      plasma glucose, and insulin and insulin-like growth factor-1 concentrations were
      greater and plasma FFA and BHB concentrations were lower in 0-d DP-L and 0-d DP-S
      cows compared with 30-d DP-S cows. Concentrate and energy intake were lower in 0
      d DP-L cows than in 0-d DP-S or 30-d DP-S cows. Milk yield and concentrations of
      plasma metabolites did not differ in wk 4 to 7, although EB was lower in wk 6 and
      7 postpartum in 0-d DP-L cows than in 0-d DP-S cows. In conclusion, a 0-d DP
      reduced milk yield and improved EB and metabolic status of cows in early
      lactation compared with a 30-d DP. Reducing the postpartum level of concentrate
      of cows with a 0-d DP did not affect fat- and protein-corrected milk yield or
      plasma FFA and BHB concentrations in early lactation but did reduce EB in wk 6
      and 7 postpartum.

PMID- 28457549
TI  - Effect of different levels of rapidly degradable carbohydrates calculated by a
      simple rumen model on performance of lactating dairy cows.
AB  - Aggregating rumen degradation characteristics of different carbohydrate
      components into the term modeled rapidly degradable carbohydrates (mRDC) can
      simplify diet formulation by accounting for differences in rate and extent of
      carbohydrate degradation within and between feedstuffs. This study sought to
      evaluate responses of lactating dairy cows to diets formulated with increasing
      levels of mRDC, keeping the supply of other nutrients as constant as possible.
      The mRDC content of feedstuffs was calculated based on a simple rumen model
      including soluble, washable, and nonwashable but potentially degradable
      fractions, as well as the fractional degradation and passage rates, of sugar,
      starch, neutral detergent fiber, and other carbohydrates. The mRDC term
      effectively represents the total amount of carbohydrates degraded in the rumen
      within 2 h after ingestion. Fifty-two lactating Holstein cows (of which 4 were
      rumen fistulated) were assigned to 4 treatments in a 4 * 4 Latin square design.
      Treatments were fed as a total mixed ration consisting of 25.4% corn silage,
      23.1% grass silage, 11.6% grass hay, and 39.9% concentrate on a dry matter basis.
      Differences in mRDC were created by exchanging nonforage neutral detergent fiber
      rich ingredients (mainly sugar beet pulp) with starch-rich ingredients (mainly
      wheat) and by exchanging corn (slowly degradable starch) with wheat (rapidly
      degradable starch) in the concentrate, resulting in 4 treatments that varied in
      dietary mRDC level of 167, 181, 194, or 208 g/kg of dry matter. Level of mRDC did
      not affect dry matter intake. Fat- and protein-corrected milk production and milk
      fat and lactose yield were greatest at 181 mRDC and decreased with further
      increases in mRDC. Milk protein yield and concentration increased with increasing
      mRDC level. Mean rumen pH and diurnal variation in ruminal pH did not differ
      between treatments. Total daily meal time and number of visits per meal were
      smaller at 181 and 194 mRDC. Despite milk production responses, increasing
      dietary mRDC levels, while maintaining net energy and intestinal digestible
      protein as well as other nutrients at similar levels, did not influence rumen pH
      parameter estimates and had minor effects on feeding behavior. These results
      indicate that aggregating rapidly degradable carbohydrate content into one term
      may be a simple way to further improve predictability of production responses in
      practical diet formulation for lactating dairy cows.

PMID- 28457551
TI  - Short communication: Comparative proteomic analysis of the lactating and
      nonlactating bovine mammary gland.
AB  - The objective of this study was to determine how bovine mammary protein profiles
      vary during lactation and the dry period. Three lactating and 3 nonlactating cows
      were selected for mammary gland tissue sampling. Compared with the mammary
      proteins in nonlactating cows, a total of 60 differentially expressed proteins
      (DEP, including 57 upregulated and 3 downregulated) were identified in lactating
      cows using 2-dimensional difference gel electrophoresis combined with mass
      spectrometry. These DEP included enzymes and proteins associated with various
      macromolecular metabolic processes, and appeared to promote the increased
      metabolic activity associated with milk synthesis and secretion. The increased
      DEP were primarily related to initiation, maintenance, and involution of
      lactation, and included proteins involved in glycolysis/gluconeogenesis, the
      tricarboxylic acid cycle, the pentose phosphate pathway, oxidative
      phosphorylation, aminoacyl-transfer RNA biosynthesis, and fatty acid
      biosynthesis. Identified DEP were further validated by real-time, reverse
      transcription PCR and Western blot. Five new DEP associated with lactation were
      uniquely identified. This work provided some protein-associated insights to
      facilitate further investigation of the mechanisms underlying lactation in dairy
      cows.

PMID- 28457550
TI  - Effects of rare sugar D-allulose on acid production and probiotic activities of
      dairy lactic acid bacteria.
AB  - It has recently been reported that the rare sugar d-allulose has beneficial
      effects, including the suppression of postprandial blood glucose elevation in
      humans, and can be substituted for sucrose as a low-calorie food ingredient. To
      examine the applications of d-allulose in the dairy industry, we investigated the
      effects of d-allulose on the acid production of 8 strains of yogurt starter
      (Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus) and 4
      strains of lactococci, including potential probiotic candidates derived from
      dairy products. Acid production by 2 L. delbrueckii ssp. bulgaricus yogurt
      starter strains in milk was suppressed by d-allulose, but this phenomenon was
      also observed in some strains with another sugar (xylose), a sugar alcohol
      (sorbitol), or both. In contrast, among the dairy probiotic candidates,
      Lactococcus lactis H61, which has beneficial effects for human skin when drunk as
      part of fermented milk, was the only strain that showed suppression of acid
      production in the presence of d-allulose. Strain H61 did not metabolize d
      allulose. We did not observe suppression of acid production by strain H61 with
      the addition of xylose or sorbitol, and xylose and sorbitol were not metabolized
      by strain H61. The acid production of strain H61 after culture in a constituted
      medium (tryptone-yeast extract-glucose broth) was also suppressed with the
      addition of d-allulose, but growth efficiency and sugar fermentation style were
      not altered. Probiotic activities-such as the angiotensin-converting enzyme
      inhibitory activity of H61-fermented milk and the superoxide dismutase activity
      of H61 cells grown in tryptone-yeast extract-glucose broth-were not affected by d
      allulose. d-Allulose may suppress acid production in certain lactic acid bacteria
      without altering their probiotic activity. It may be useful for developing new
      probiotic dairy products from probiotic strains such as Lactococcus lactis H61.

PMID- 28457552
TI  - Lactation performance of Holstein cows treated with 2 formulations of recombinant
      bovine somatotropin in a large commercial dairy herd in Brazil.
AB  - The objectives of this controlled study were to compare the effects of 2
      different formulations of recombinant bovine somatotropin (rbST) on milk yield,
      milk composition (fat and protein), milk somatic cell count, and body condition
      score (BCS) among dairy cattle in a large commercial herd. Regulatory approved
      500-mg zinc sesame oil base rbST (ZSO-rbST; Elanco Animal Health, Greenfield, IN)
      and vitamin E lecithin base rbST (VEL-rbST; LG Life Sciences, Seoul, South Korea)
      formulations were administered per the manufacturers' recommendations every 14 d
      over 17 injection cycles starting at 57 to 70 d of lactation (90 cows per rbST
      group). Control cows (n = 60) received no rbST. Somatotropin-treated animals (VEL
      rbST and ZSO-rbST combined) had increased average milk yield and protein
      percentage and lower average BCS compared with control cows. For primiparous
      cows, average milk yield was 37.75 kg/d with the ZSO-rbST treatment and 35.72
      kg/d with the VEL-rbST treatment. For multiparous cows, average milk yield was
      40.13 kg/d with the ZSO-rbST treatment and 38.81 kg/d with the VEL-rbST
      treatment. There were no differences in milk fat percentage between VEL-rbST and
      ZSO-rbST treatments, but milk protein content was greater with VEL-rbST treatment
      than with ZSO-rbST treatment. Nonetheless, cows treated with ZSO-rbST yielded
      more kilograms of fat and protein per day than cows treated with VEL-rbST. No
      significant differences in BCS were found between both rbST treatment groups. The
      differential increase in milk yield between cows treated with ZSO-rbST and VEL
      rbST was driven by rbST response differences both within the 14-d cycle and
      throughout the 17 injection cycles. The cows treated with VEL-rbST demonstrated a
      more variable 14-d milk yield response curve, with more pronounced valleys
      between injections compared with the ZSO-rbST formulation. In addition, only the
      ZSO-rbST treatment was effective in modifying the lactation persistency compared
      with control cows. Compared with the VEL-rbST formulation, the ZSO-rbST
      formulation yielded more kilograms of milk, fat, and protein with less milk
      variation throughout the seventeen 14-d lactation cycles for both primiparous and
      multiparous cows.

PMID- 28457553
TI  - Effect of source of trace minerals in either forage- or by-product-based diets
      fed to dairy cows: 1. Production and macronutrient digestibility.
AB  - Excess rumen-soluble Cu and Zn can alter rumen microbial populations and reduce
      fiber digestibility. Because of differences in particle size and chemical
      composition, ruminal and total-tract digestibility of fiber from forage- and by
      product-based diets can differ. We hypothesized that, because of differences in
      mineral solubility, diets with hydroxy rather than sulfate trace minerals would
      have greater fiber digestibility, but the effect may depend on source of fiber.
      Eighteen multiparous cows were used in a split-plot replicated Latin square with
      two 28-d periods to evaluate the effects of Cu, Zn, and Mn source (sulfates or
      hydroxy; Micronutrients USA LLC, Indianapolis, IN) and neutral detergent fiber
      (NDF) source (forage diet = 26% NDF vs. by-product = 36%) on total-tract nutrient
      digestibility. During the entire experiment (56 d) cows remained on the same
      fiber treatment, but source of supplemental trace mineral was different for each
      28-d period so that all cows were exposed to both mineral treatments. During each
      of the two 28-d periods, cows were fed no supplemental Cu, Zn, or Mn for 16 d
      followed by 12 d of feeding supplemental Cu, Zn, and Mn from either sulfates or
      hydroxy sources. Supplemental minerals for each of the mineral sources fed
      provided approximately 10, 35, and 32 mg/kg of supplemental Cu, Zn, and Mn,
      respectively, for both fiber treatments. Total dietary concentrations of Cu, Zn,
      and Mn were approximately 19, 65, and 70 mg/kg for the forage diets and 21, 85,
      and 79 mg/kg for the by-product diets, respectively. Treatment had no effect on
      dry matter intake (24.2 kg/d) or milk production (34.9 kg/d). Milk fatty acid
      profiles were altered by fiber source, mineral source, and their interaction.
      Cows fed the by-product diets had lower dry matter (65.9 vs. 70.2%), organic
      matter (67.4 vs. 71.7%), and crude protein digestibility (58.8 vs. 62.1%) but
      greater starch (97.5 vs. 96.3%) and NDF digestibility (50.5 vs. 44.4%) compared
      with cows fed the forage treatment. Feeding increased concentrations of by
      products decreased total digestible nutrients regardless of mineral source.
      Feeding hydroxy Cu, Zn, and Mn increased NDF digestibility (48.5 vs. 46.4%) but
      had no effect on total digestible nutrients.

PMID- 28457554
TI  - Comparison between an exclusive in vitro-produced embryo transfer system and
      artificial insemination for genetic, technical, and financial herd performance.
AB  - The objective of this study was to implement an in vitro-produced embryo transfer
      (IVP-ET) system in an existing stochastic dynamic dairy simulation model with
      multitrait genetics to evaluate the genetic, technical, and financial performance
      of a dairy herd implementing an exclusive IVP-ET or artificial insemination (AI)
      system. In the AI system, sexed semen was used on the genetically best heifers
      only. In the IVP-ET system, all of the animals in the herd were impregnated with
      female sexed embryos created through in vitro fertilization of oocytes collected
      from animals of superior genetics for different traits of interest. Each donor
      was assumed to yield on average 4.25 transferable embryos per collection. The
      remaining animals in the herd were used as recipients and received either a fresh
      embryo or a frozen embryo when fresh embryos were not available. Selection of
      donors was random or based on the greatest estimated breeding value (EBV) of
      lifetime net merit (NM$), milk yield, or daughter pregnancy rate. For both the
      IVP-ET and AI systems, culling of surplus heifer calves not needed to replace
      culled cows was based on the lowest EBV for the same traits. A herd of 1,000
      milking cows was simulated 15 yr over time after the start of the IVP-ET system.
      The default cost to produce and transfer 1 embryo was set at $165. Prices of
      fresh embryos at which an exclusive IVP-ET system financially breaks even with
      the comparable AI system in yr 15 and for an investment period of 15 yr were also
      estimated. More surplus heifer calves were sold from the IVP-ET systems than from
      the comparable AI systems. The surplus calves from the IVP-ET systems were also
      genetically superior to the surplus calves from the comparable AI systems, which
      might be reflected in their market value as a premium price. The most profitable
      scenario among the 4 IVP-ET scenarios in yr 15 was the one in which NM$ was
      maximized in the herd. This scenario had an additional profit of $8/cow compared
      with a similar AI scenario that maximized NM$, provided that surplus heifer
      calves could be sold at a premium price based on the superiority of the EBV of
      NM$. For the IVP-ET system to be at least as profitable as the comparable AI
      system during a 15-yr investment period, the surplus calves from the IVP-ET
      system needed to be sold at the premium prices. The break-even price of fresh
      embryos was estimated to be $84 for the exclusive IVP-ET system. This resulted in
      the same profit as the AI system, which maximized NM$ for a 15-yr investment
      period and in which heifer calves were sold at a premium price.

PMID- 28457555
TI  - Polycyclic aromatic hydrocarbons (PAHs) at the Gulf of Kutch, Gujarat, India:
      Occurrence, source apportionment, and toxicity of PAHs as an emerging issue.
AB  - The present study extrapolates the assessment and characterization of a barely
      studied region, the Gulf of Kutch, (near Jamnagar), Gujarat, India, in terms of
      PAH exposure, adverse effects caused by them, and various toxicological indices
      showing the catastrophic effects of their elevated concentrations. SigmaPAH
      concentration in the site ranged from 118,280 to 1,099,410ngg-1 dw, with a
      predominance of 2-3-ring PAHs (79.09%) as compared to 4-5- and 6-ring PAHs
      (20.91%). The concentrations of carcinogenic PAHs were found to be between 8120
      and 160,000ngg-1 dw, with a mean of 63,810ngg-1 dw, which is much higher than
      normal acceptable values. The toxic equivalent quotient for 6CPAHs ranged from
      150.47 to 26,330ngg-1 BaPeq, encompassing 50.63% of SigmaPAH toxicity. This
      toxicological profile of the present study site would be of paramount importance
      as it offers fresh information regarding the load of legacy pollutants such as
      PAHs and the inputs and methods to cope with their extremely high concentrations
      in less explored marine habitats.

PMID- 28457556
TI  - Source apportionment of sediment organic material in a semi-enclosed sea using
      Bayesian isotopic mixing model.
AB  - To determine sources of organic material in semi-enclosed Bohai Sea, samples of
      marine surface sediments, suspended particulates in adjacent rivers and
      atmospheric deposition were collected and analyzed for grain size composition,
      total organic carbon(TOC and POC), total nitrogen (TN and PN), and stable
      isotopic composition (delta13C and delta15N). Measured bulk C/N ratio (5.50
      12.28), delta13C (-23.59~-19.540/00), and delta15N (2.80-8.070/00) values of
      surface sediment organic materials indicated a mixed source of marine and
      terrestrial contributions. Spatial distribution of organic C, N and their stable
      isotope composition indicated a land-sea gradient of organic material content and
      source combination. Using MixMIR model with dual isotopes, it was estimated that
      relative contributions of marine, riverine, and atmospheric sources to sediment
      mixture were 69.0%, 9.6%, and 21.4%, respectively. Our results demonstrated the
      advantage of Bayesian isotope mixing models over the conventional end-member
      mixing models for source apportionment in coastal seas with complex source
      origins.

PMID- 28457557
TI  - Evidence of chronic anthropogenic nutrient within coastal lagoon reefs adjacent
      to urban and tourism centers, Kenya: A stable isotope approach.
AB  - The source of anthropogenic nutrient and its spatial extent in three fringing
      reefs with differing human population gradients in Kenya were investigated using
      stable isotope approaches. Nutrient concentrations and nitrate-delta15N in
      seepage water indicated that population density and tourism contributed greatly
      to the extent of nutrient loading to adjacent reefs. Although water-column
      nutrient analyses did not show any significant difference among the reefs, higher
      delta15N and N contents in macrophytes showed terrestrial nutrients affected
      primary producers in onshore areas in Nyali and Bamburi reefs, but were mitigated
      by offshore water intrusion especially at Nyali. On the offshore reef flat, where
      the same species of macroalgae were not available, complementary use of delta15N
      in sedimentary organic matter suggested inputs of nutrients originated from the
      urban city of Mombasa. If population increases in the future, nutrient conditions
      in the shallower reef, Vipingo, may be dramatically degraded due to lower water
      exchange ratio.

PMID- 28457558
TI  - Geochemical markers of sedimentary organic matter in Todos os Santos Bay, Bahia -
      Brazil. Indicators of sources and preservation.
AB  - Natural stable isotopes, such as carbon (C) and nitrogen (N), are modern tools to
      assess geochemical processes. C and N in organic matter can carry fingerprints of
      their hydrologic flows and sedimentary processes, including any anthropogenic
      modification on the natural system. This study focuses on the determination of
      aliphatic and polycyclic aromatic hydrocarbons and isotopic ratio in the sediment
      of Todos os Santos Bay (TSB). The isotopic results of the total organic matter
      indicate varied contribution marine and terrigenous. Typical rates of PAHs mainly
      indicate a pyrogenic source and mixture between pyrogenic and petrogenic sources.
      Typical ratios for the n-alkanes indicate the presence of petroleum hydrocarbons.
      The isotopic composition of n-alkanes suggests a mixture of sources, with the
      possible contribution of petrogenic.

PMID- 28457559
TI  - Periodic limb movements of sleep are associated with an increased prevalence of
      atrial fibrillation in patients with mild sleep-disordered breathing.
AB  - BACKGROUND: Growing evidence indicates that periodic limb movements of sleep
      (PLMS) may be related to increased risk of developing cardiovascular disease.
      However, the association of PLMS with atrial fibrillation (AF) is unclear,
      especially in patients with sleep-disordered breathing (SDB). This study sought
      to investigate whether PLMS were associated with increased AF prevalence,
      independent of established risk factors. METHODS: We performed a cross-sectional
      study of patients who underwent attended polysomnography at Mayo Clinic from 2011
      to 2014. The association of PLMS with AF prevalence was estimated by using
      logistic regression models. RESULTS: 15,414 patients were studied, 76.3% of
      individuals with SDB defined by apnea-hypopnea index (AHI) >=5/h, and 15.3% with
      a diagnosis of AF. In univariate logistic modelling, individuals with periodic
      limb movement index (PLMI) >=30/h had higher odds of AF (odds ratio [OR] 1.96,
      95% confidence interval [CI]1.79-2.16, p<0.001) when compared to patients with
      PLMI <15/h. After multivariate adjustment (for age, race, sex, history of
      smoking, hypertension, diabetes, coronary artery disease, heart failure,
      cerebrovascular disease, renal disease, iron deficiency anemia, chronic
      obstructive pulmonary disease, AHI, arousal index), in mild SDB patients, a PLMI
      >=30/h or periodic limb movement arousal index (PLMAI) >=5/h had significantly
      higher odds of AF than those with PLMI <15/h (OR 1.21, 95% CI 1.00-1.47, p=0.048)
      or PLMAI <1/h (OR 1.27, 95% CI 1.03-1.56, p=0.024). CONCLUSIONS: Frequent PLMS
      are independently associated with AF prevalence in patients with mild SDB.
      Further studies are needed to better understand the relationship with incident
      AF.

PMID- 28457560
TI  - Three-year follow-up of patients with acetylcholine-induced coronary artery spasm
      combined with insignificant coronary stenosis.
AB  - BACKGROUND: Coronary artery spasm (CAS) and significant coronary stenosis are
      known to be major causes of myocardial ischemia. However, their association and
      the impact of insignificant coronary stenosis (ICS) on long-term clinical
      outcomes of CAS patients are largely unknown. METHODS: A total of 2797 patients
      without significant coronary artery disease (CAD) who underwent the acetylcholine
      (ACH) provocation test between November 2004 and October 2010 were enrolled.
      Significant CAS was defined as having >=70% of temporary narrowing by ACH test
      and ICS as having <70% of fixed stenosis on angiography. Patients were divided
      into two groups: ICS group (n=764) and non-ICS group (n=845). To adjust potential
      confounders, a propensity score matching (PSM) analysis was performed using the
      logistic regression model. Primary endpoint was the composite of total death,
      myocardial infraction (MI), de novo percutaneous coronary intervention (PCI), and
      cerebrovascular accidents (CVA). Secondary endpoint was the incidence of
      recurrent angina requiring repeat coronary angiography (CAG) at 3years. RESULTS:
      After PSM analysis, two well-balanced groups (548 pairs, total=1096) were
      generated. The baseline clinical characteristics were similar between the two
      groups. During the ACH test, compared with the non-ICS group, the ICS group had
      smaller spastic narrowing diameter (0.69+/-0.35 vs. 0.73+/-0.37, P=0.039) and
      incidence of ST-segment depression (4.0% vs. 0.9%, P=0.001). The incidence of
      primary and secondary endpoints was similar between the two groups up to 3years.
      CONCLUSIONS: Although, the ICS group was expected to have more adverse long-term
      clinical outcomes, it was not associated with the increased incidence of major
      adverse clinical outcomes compared with the non-ICS group up to 3years. Longer
      term follow-up studies are needed.

PMID- 28457561
TI  - Is the presence of end-diastolic forward flow specific for restrictive right
      ventricular physiology in repaired tetralogy of Fallot?
AB  - BACKGROUND: End-diastolic forward flow (EDFF) is recognized as restrictive right
      ventricular physiology (r-RVP), but conflicting results have been reported about
      effects on the clinical outcome in repaired tetralogy of Fallot (r-TOF).
      OBJECTIVES: We hypothesized that the EDFF by Doppler was not specific for
      diagnosing r-RVP. METHODS: Sixty-two consecutive patients aged 15.7+/-11.6years
      who underwent cardiac catheterization were studied. Patients were divided
      according to the presence of EDFF (group 1: EDFF+, group 2: EDFF-) and RV size
      (group A: small RV, group B: large RV [>150ml/m2]). RESULTS: Group 1 (n=23) had
      higher a right atrial pressure (RAP), pressure gradient between the RAP and
      pulmonary diastolic pressure (PDP), and atrial natriuretic peptide (ANP) levels
      than group 2. Four patients (17.4%) in group 1 and 89.7% of patients in group 2
      had a normal RAP range (a wave<10mmHg). There were no differences in the RV
      volume, ejection fraction (EF), B-type natriuretic peptide levels, and severity
      of pulmonary regurgitation (PR) between groups 1 and 2. Group A had better RV and
      LVEF than group B, as well as a smaller LV size. The RAP in subgroup 1A was
      higher than that of the other 3 subgroups. Subgroup 1B had a similar RAP to group
      2, and a lower PDP and a more severe PR than subgroup 1A. CONCLUSIONS: Patients
      with EDFF are associated with increased ANP levels. The presence of EDFF may not
      be specific for r-RVP, since it is observed in some TOF patients with low PDP
      (severe PR) and normal RAP.

PMID- 28457562
TI  - Complications after implantation of a new-generation insertable cardiac monitor:
      Results from the LOOP study.
AB  - BACKGROUND: Insertable cardiac monitors (ICM) are leadless devices utilized in
      long-term monitoring of the heart rhythm. The implantation procedure of the new
      generation ICMs is minimally invasive, but little experience exists regarding
      complications. We thus aimed to investigate adverse events (AE) according to
      procedure-related characteristics after implantation of a large number of new
      generation ICMs. METHODS: The study population consisted of participants
      randomized to receive ICM in a multi-center trial. The Reveal LINQTM ICM was
      implanted using provided insertion tools, either in an electrophysiology
      laboratory or outpatient procedure room. If device sensing was insufficient in
      the first subcutaneous position, one or more repositions were performed. Patients
      were urged to make contact if they suspected any AE. Furthermore, follow-up for
      safety endpoints consisted of evaluation of medical records and planned study
      visits. RESULTS: 1420 patients received an ICM, 753 (53%) in a procedure room and
      667 (47%) in an electrophysiology laboratory. During a median follow-up of
      499days, 9 (0.63%) and 15 (1.13%) patients experienced AEs with and without need
      for device explantation, respectively. In the 38 patients requiring device
      repositioning, more AEs requiring explantation were seen (3 (7.9%) vs. 6 (0.4%),
      p=0.001). Patients undergoing implantation in a procedure room had more
      infections (12 (1.6%) vs. 1 (0.1%), p=0.004), though no significant difference
      was reached in AEs requiring explantation (7 (0.9%) vs. 2 (0.3%), p=0.19).
      CONCLUSION: The Reveal LINQTM ICM can be inserted with a very low risk of
      complications, both in the traditional electrophysiology laboratory setting and
      in an outpatient procedure room.

PMID- 28457563
TI  - Oral care with chlorhexidine gluconate: Time to focus on outcomes that matter.

PMID- 28457564
TI  - The added value of laboratory markers to mortality risk scores in acute pulmonary
      embolism.

PMID- 28457565
TI  - Response to a letter to the editor "Ultrasound assessment of optic nerve sheath
      diameter in healthy volunteers".

PMID- 28457566
TI  - Forward.

PMID- 28457567
TI  - Foreword.

PMID- 28457568
TI  - Child Neurology Training for Pediatricians.

PMID- 28457569
TI  - Increasing age in Achilles rupture patients over time.
AB  - BACKGROUND: The changing demographics of Achilles tendon rupture (ATR) patients
      have not fully been investigated. However, there has been a general suspicion
      that this injury is occurring in an increasingly older population, in terms of
      mean age. The aim of this study was to objectively show an increase in age in
      Achilles tendon rupture patients over time. METHODS: Published literature on
      Achilles tendon ruptures was searched for descriptive statistics on the
      demographics of patients in the studies, specifically mean and median age of
      Achilles tendon rupture patients, gender ratio, percentage of athletics-related
      injuries, percentage of smokers, and BMI. Linear regression analyses were
      performed to determine the trend of patient demographics over time. A Welch one
      way ANOVA was carried out to identify any possible differences in data obtained
      from different types of studies. RESULTS: The patient demographics from 142
      studies were recorded, with all ATR injuries occurring between the years 1953 and
      2014. There was no significant difference in the mean age data reported by
      varying study types, i.e. randomized controlled trial, cohort study, case series,
      etc. (P=0.182). There was a statistically significant rise in mean age of ATR
      patients over time (P<0.0005). There was also a statistically significant drop in
      percentage of male ATR patients (P=0.02). There is no significant trend for
      percentage of athletics-related injuries, smoking or BMI. CONCLUSION: Since 1953
      to present day, the mean age at which ATR occurs has been increasing by at least
      0.721 years every five years. In the same time period, the percentage of female
      study patients with ATR injuries has also been increasing by at least 0.6% every
      five years. LEVEL OF EVIDENCE: Level III; Retrospective cohort study.

PMID- 28457570
TI  - [Psychoactive effects of 'legal high': About lysergic acid amide (LSA)].
AB  - Lysergic acid amide (LSA) is a natural psychoactive substance consumed as a
      psychedelic drug. In 2016, 4 cases were reported to the Toulouse Addictovigilance
      Centre, resulting in unintended psychic effects and led to a hospitalisation in 2
      cases. Other cases of serious LSA intoxication are published, including a death.
      It is important to inform about the risks related to LSA consumption, a substance
      which is freely available and sometimes hidden behind various plant names.

PMID- 28457571
TI  - [Acute analgesic effect of paracetamol in primary care: Incomplete evidence].
AB  - This meta-analysis assessed the analgesic effect of a single oral dose of
      paracetamol versus placebo in adults, in primary care. Parallel randomized
      studies were searched on MEDLINE(r), CENTRAL(r), and EMBASE(r). We found five
      studies on sore throat (842 patients) and 12 studies on headache (3433 patients).
      None related to low back pain. Regardless of the outcome, paracetamol was
      superior to placebo (number need to treat [NNT]=4-5; standardized mean difference
      [SMD]=0.51-0.92). Additional clinical trials in other primary care conditions,
      like low back pain, must be conducted.

PMID- 28457572
TI  - Analytical interference during cefepime therapeutic drug monitoring in intensive
      care patient: About a case report.
AB  - beta-lactams therapeutic drug monitoring (TDM) appears as an essential tool to
      ensure the achievement of pharmacokinetic-pharmacodynamic targets and prevent
      induced toxicity in intensive care unit patients. Indeed, those patients exhibit
      important pharmacokinetic variabilities that could lead to unpredictable plasma
      concentrations, potentially associated with poor clinical outcome, development of
      antibiotic resistance or increased side effects. Here, we report the case of a 48
      year-old-patient admitted to intensive care unit and treated by cefepime using
      TDM. Due to inconsistency between observed cefepime plasma concentrations and
      patient clinical examination, investigations were started. After analytical
      tests, we highlighted an underlying analytical interference that overestimated
      cefepime plasma concentration with our in-house high performance liquid
      chromatography with ultraviolet detection (HPLC-UV) method. Only the inadequacy
      between plasmatic concentration and patient situation alerted pharmacologists and
      clinicians. As we found no previous case in literature, we believe this report
      must serve as an example of analytical limits that required pharmacologist
      awareness and expertise in TDM realization.

PMID- 28457573
TI  - Editorial Comment.

PMID- 28457574
TI  - Botanists in Lithuania during the Michurinist Campaign.
AB  - The meeting of the Lenin All-Union Academy of Agricultural Sciences (VASKhNIL)
      that occurred from July 31 to August 7, 1948, declared Michurinism to be the only
      "correct theory" of biology in the Soviet Union. As of that moment, Michurinist
      biology officially took center stage in Soviet scientific institutions, and it
      was further developed over the next fifteen years. Scientists from all of the
      former Soviet Republics participated in the Michurinist campaign. In Lithuania,
      this campaign started in the autumn of 1948. From 1948 until 1963, the Department
      of Michurinist Biology was active at Vilnius University. Studies in this field
      were performed at Lithuanian scientific institutions, and scientists were engaged
      with this theory. This essay illustrates the realization of the Michurinist
      campaign in Lithuania using details from botany. It describes the investigations
      of plant genetics in Lithuania before World War II, depicts the general situation
      of scientists in Lithuania during the first years of the Soviet occupation,
      explores the involvement of botanists in propagating Michurinist biology, and in
      summary, reveals the peculiarities of this campaign in Lithuania.

PMID- 28457576
TI  - Effect of Concentrated Psychiatric Education on Perceived Competence to Care for
      Behavioral Health Patients.
AB  - CONTRIBUTION TO EMERGENCY NURSING PRACTICE: ABSTRACT INTRODUCTION: Increasing
      numbers of behavioral patients are presenting to emergency departments, where
      competency of staff to care for this group is unknown. METHODS: This pre-post
      study measured the effects of a 7-hour conference on perceived competency of
      nurses and allied health professionals to care for behavioral health (BH)
      patients, as measured by the 23-item Behavioral Health Care Competency (BHCC)
      survey. RESULTS: Of 102 participants, most were emergency nurses (72%), acute
      care nurses and case managers (20%), and allied health personnel (trauma
      technicians and paramedics) (8%). Before the conference, participants had
      moderate average perceived competency in caring for BH patients. BHCC scores
      differed significantly by job category, with emergency nurses scoring higher than
      did nonemergency nurses and allied health personnel. Overall competence of
      participants increased significantly after the conference. The effect size, as
      reflected by partial eta squared, was 0.265. Significant increases in scores from
      before to after the conference occurred for the total BHCC and 2 competencies:
      practice/intervention and resource adequacy. DISCUSSION: This study provides
      needed research demonstrating improved perceived competency of nurses and allied
      health professionals to care for BH patients in emergency departments after brief
      concentrated education. Improvements occurred despite the fact that participants
      had initial baseline competencies that were higher than those of general hospital
      nurses from a historical sample.

PMID- 28457575
TI  - Objective analysis of the topological organization of the human cortical visual
      connectome suggests three visual pathways.
AB  - The cortical visual system is composed of many areas serving various visual
      functions. In non-human primates, these are broadly organised into two distinct
      processing pathways: a ventral pathway for object recognition, and a dorsal
      pathway for action. In humans, recent theoretical proposals suggest the possible
      existence of additional pathways, but direct empirical evidence has yet to be
      presented. Here, we estimated the connectivity patterns between 22 human visual
      areas using resting-state functional MRI data of 470 individuals, leveraging the
      unprecedented data quantity and quality of the Human Connectome Project and a
      novel probabilistic atlas. An objective, data-driven analysis into the
      topological organisation of connectivity and subsequent quantitative confirmation
      revealed a highly significant triple dissociation between the retinotopic areas
      on the dorsal, ventral and lateral surfaces of the human occipital lobe. This
      suggests that the functional organisation of the human visual system involves not
      two but three cortical pathways.

PMID- 28457577
TI  - Proton beam radiotherapy as part of comprehensive regional nodal irradiation for
      locally advanced breast cancer.
AB  - PURPOSE: This study evaluates acute toxicity outcomes in breast cancer patients
      treated with adjuvant proton beam therapy (PBT). METHODS: From 2011 to 2016, 91
      patients (93 cancers) were treated with adjuvant PBT targeting the intact
      breast/chest wall and comprehensive regional nodes including the axilla,
      supraclavicular fossa, and internal mammary lymph nodes. Toxicity was recorded
      weekly during treatment, one month following treatment, and then every 6months
      according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
      Charts were retrospectively reviewed to verify toxicities, patient parameters,
      disease and treatment characteristics, and disease-related outcomes. RESULTS:
      Median follow-up was 15.5months. Median PBT dose was 50.4 Gray relative
      biological effectiveness (GyRBE), with subsequent boost as clinically indicated
      (N=61, median 10 GyRBE). Chemotherapy, when administered, was given adjuvantly
      (N=42) or neoadjuvantly (N=46). Grades 1, 2, and 3 dermatitis occurred in 23%,
      72%, and 5%, respectively. Eight percent required treatment breaks owing to
      dermatitis. Median time to resolution of dermatitis was 32days. Grades 1, 2, and
      3 esophagitis developed in 31%, 33%, and 0%, respectively. CONCLUSIONS: PBT
      displays acceptable toxicity in the setting of comprehensive regional nodal
      irradiation.

PMID- 28457578
TI  - An approach to design controllers for MIMO fractional-order plants based on
      parameter optimization algorithm.
AB  - The parameter optimization method for multivariable systems is extended to the
      controller design problems for multiple input multiple output (MIMO) square
      fractional-order plants. The algorithm can be applied to search for the optimal
      parameters of integer-order controllers for fractional-order plants with or
      without time delays. Two examples are given to present the controller design
      procedures for MIMO fractional-order systems. Simulation studies show that the
      integer-order controllers designed are robust to plant gain variations.

PMID- 28457579
TI  - Amyloidosis and neurodegeneration result in distinct structural connectivity
      patterns in mild cognitive impairment.
AB  - Alzheimer's disease (AD) is increasingly considered as a disconnection syndrome.
      Previous studies of the structural connectome in early AD stages have focused on
      mild cognitive impaired subjects (MCI), considering them as a homogeneous group.
      We studied 168 subjects from the Alzheimer's Disease Neuroimaging Initiative
      database (116 MCI and 52 cognitively normal subjects). Biomarker-based
      stratification using amyloid biomarkers (AV45 PET) and neurodegeneration
      biomarkers (MRI and FDG PET) led to 4 subgroups based on amyloid positivity (A+/
      ) and neurodegeneration positivity (N+/-): A-N-, A+N-, A-N+, and A+N+. Using
      diffusion MRI, we showed that both MCI A-N+ and MCI A+N+ subjects displayed an
      alteration of the white matter in the fornix and a significant bihemispheric
      network of decreased connections. These network alterations in MCI A+N+ are
      stronger and more focal than those of MCI A-N+. Only MCI A+N+ subjects exhibited
      specific changes in hippocampal connectivity and an AD-like alteration pattern.
      Our results indicate that the connectome disintegration pattern of MCI subgroups
      differ with respect to brain amyloid and neurodegeneration. Each of these 2 AD
      biomarkers induces a connectome alteration that is maximal when they coexist.

PMID- 28457581
TI  - Attitudes, beliefs, and perceived norms about corporal punishment and related
      training needs among members of the "American Professional Society on the Abuse
      of Children".
AB  - Hitting children for disciplinary purposes (i.e., spanking or corporal punishment
      [CP]) is a strong risk factor for child physical abuse and is highly prevalent in
      the U.S. Yet, little is currently known about the relevant attitudes, beliefs, or
      training needs of key professionals who often advise parents regarding child
      discipline strategies. A survey of the American Professional Society on the Abuse
      of Children (APSAC) membership, comprised of mental health professionals,
      physicians, child welfare professionals, and other professionals in the child
      maltreatment field, was conducted to assess attitudes, beliefs, perceived norms,
      training needs, and motivations to change norms regarding CP (N=571, response
      rate=51%). Most respondents agreed that spanking is a bad disciplinary technique
      (82%), is harmful for children (74%), and leads to negative outcomes (M=3.0,
      SD=0.6) more frequently than positive outcomes (M=2.1, SD=0.6; t=20.8; p<0.0001)
      for children. Professionals reported perceiving that their colleagues' level of
      endorsement of CP (M=2.4, SD=1.0) was higher than their own (M=1.9, SD=1.0;
      t(568)=-10.7, p<0.0001) though still below the midpoint. Professionals reported
      high levels of preparedness to effectively advise parents on non-physical child
      discipline strategies, but reported perceiving lower levels of preparedness
      amongst their colleagues. They reported highly valuing giving such advice to
      parents and being very motivated to participate in activities designed to change
      social norms regarding CP. Most APSAC members are poised to change these norms
      and, in doing so, to help reduce rates of child physical abuse in the U.S.

PMID- 28457582
TI  - Clinical and sociodemographic profile of epilepsy in adults from a reference
      centre in Colombia.
AB  - OBJECTIVES: To describe the sociodemographic and clinical characteristics of a
      cohort of patients with epilepsy from a reference centre in Colombia. METHODS:
      Cross-sectional study including patients diagnosed with epilepsy who attended our
      epilepsy centre (Neurocentro) between 2013 and 2016. Data were gathered from
      patients' medical histories. RESULTS: We gathered data from a total of 354
      patients diagnosed with epilepsy. Median age was 37 years; 52% were men. Seizures
      were focal in 57% of the patients and generalised in 38%; seizure type was not
      determined in 6% of the sample. The most frequent aetiology was cryptogenic
      (21%), followed by traumatic (14%). Median time of disease progression and age at
      onset were 23 and 11 years, respectively. Psychiatric comorbidities were found in
      18% of the patients and 40% had some degree of cognitive impairment. Around 40%
      of our sample reported adverse reactions to antiepileptic drugs at some point
      during treatment. Antiepileptic drugs were administered in monotherapy in 36% of
      the patients. Around 37% had drug-resistant epilepsy and 14% underwent surgery.
      CONCLUSIONS: Psychiatric comorbidities, cognitive impairment, adverse drug
      reactions, and drug-resistant epilepsy are common among epileptic patients in
      Colombia. Knowledge of the factors with an impact on epilepsy may lay the
      foundations for improving management of these patients on the administrative
      level and improving quality of life.

PMID- 28457580
TI  - TMEM230 in Parkinson's disease.
AB  - A study on familial Parkinson disease (PD) described 4 variants in the gene
      TMEM230 (Chr. 20p13) as the cause of PD. The aim of this study was to test if
      variants in the TMEM230 gene are associated with PD in 2 independent American
      European data sets. No variants in the TMEM230 region were found associated with
      PD, age at onset, or cerebrospinal fluid alpha-synuclein levels.

PMID- 28457583
TI  - From 'Legionellosis acquired through a dental unit' to 'Was Legionellosis
      acquired through a dental unit?'

PMID- 28457584
TI  - Prophylactic lower para-aortic irradiation using intensity-modulated radiotherapy
      mitigates the risk of para-aortic recurrence in locally advanced cervical cancer:
      A 10-year institutional experience.
AB  - OBJECTIVE: To evaluate the effects of prophylactic sub-renal vein radiotherapy
      (SRVRT) using intensity-modulated radiotherapy (IMRT) for cervical cancer.
      METHODS: A total of 206 patients with FIGO stage IB2-IVA cervical cancer and
      negative para-aortic lymph nodes (PALNs) who underwent pelvic IMRT (PRT) or SRVRT
      between 2004 and 2013 at our institution were reviewed. SRVRT cranially extended
      the PRT field for PALNs up to the left renal vein level. The prescribed dose was
      consistent 50.4Gy in 28 fractions. RESULTS: Overall, 110 and 96 patients
      underwent PRT and SRVRT, respectively. The SRVRT group had more advanced disease
      based on FIGO stage and positive pelvic lymph nodes (PLNs). The median follow-up
      time was 60months (range, 7-143). For the total study population, the 5-year PALN
      recurrence-free survival (PARFS) and overall survival (OS) for PRT vs. SRVRT were
      87.6% vs. 97.9% (p=0.03) and 74.5% vs. 87.8% (p=0.04), respectively. In patients
      with FIGO III-IVA or positive PLNs, the 5-year PARFS and OS for PRT vs. SRVRT
      were 80.1% vs. 96.4% (p=0.02) and 58.1% vs. 83.5% (p=0.012), respectively.
      However, there were no significant differences in these outcomes for patients
      with FIGO IB-IIB and negative PLNs. In a multivariate analysis, only SRVRT was
      associated with better PARFS (HR, 0.21; 95% CI, 0.06-0.78; p=0.02). The SRVRT did
      not significantly increase severe late toxicities. CONCLUSION: Prophylactic SRVRT
      using IMRT reduced PALN recurrence with tolerable toxicities, supporting the
      application of risk-based radiation fields for cervical cancer.

PMID- 28457585
TI  - [The parapharyngeal adipose corpus: Surgical anatomy and imaging].
AB  - : The aim of this study is to define the parapharyngeal adiposis corpus (PAC) and
      its anatomical relationships originally described by P. Sebileau in 1892 to
      assess the potential clinical implications. MATERIALS AND METHODS: Seven frozen
      fresh cadavers were used, 3 of which after injection of latex neoprene colored in
      cervicocephalic arterial network. A MRI was performed in 10 patients without
      cervical pathology. The analysis was done on the frontal and transverse T1
      weighted sections. RESULTS: The PAC, which is a yellowish fat formation, fills
      the paratonsillar space. It measures an average of 4.8cm (4.5 to 5.2cm) in length
      and 1.2cm (1.1 to 1.5cm) for subjects of varying size and sex. Its arterial
      supply is mainly provided by the ascending palatine artery, an early branch of
      the facial artery. A left-right symmetry was found on MRI analyses regardless of
      sex or age. It is found in all the medial and ventral cases on the pharyngeal
      extension of the parotid gland in homogeneous hyperintense T1. CONCLUSION: The
      PAC is a constant fat structure. Its vascularization depends mainly on the
      ascending palatine artery. Through its association with fatty peripharyngeal
      space, it could be a functionally sliding space. In imaging, it may be helpful in
      the interpretation of images of the pharyngeal extension of the parotid gland
      tumors.

PMID- 28457586
TI  - Adaptation of the vertical vestibulo-ocular reflex in cats during low-frequency
      vertical rotation.
AB  - OBJECTIVE: We examined plastic changes in the vestibulo-ocular reflex (VOR)
      during low-frequency vertical head rotation, a condition under which otolith
      inputs from the vestibular system are essential for VOR generation. METHODS: For
      adaptive conditioning of the vertical VOR, 0.02Hz sinusoidal pitch rotation for
      one hour about the earth's horizontal axis was synchronized with out-of-phase
      vertical visual stimulation from a random dot pattern. RESULTS: A vertical VOR
      was well evoked when the upright animal rotated around the earth-horizontal axis
      (EHA) at low frequency due to the changing gravity stimulus and dynamic
      stimulation of the otoliths. After adaptive conditioning, the amplitude of the
      vertical VOR increased by an average of 32.1%. CONCLUSION: Our observations
      showing plasticity in the otolithic contribution to the VOR may provide a new
      strategy for visual-vestibular mismatch training in patients with otolithic
      disorders. This low-frequency vertical head rotation protocol also provides a
      model for investigating the mechanisms underlying the adaptation of VORs mediated
      by otolith activation.

PMID- 28457587
TI  - Integration of mental health screening in the management of patients with
      temporomandibular disorders.
AB  - Mental health disorders such as depression or anxiety, or both, are more common
      in patients with temporomandibular disorders (TMD) (16%-40%) than in the general
      population (16%), and failure to recognise them may be detrimental to the
      management of TMD. Paper-based screening tools previously reported in this group
      require assessment by clinicians and subsequent collation of data. We describe
      our experience of a new system - IMPARTS (Integrating mental and physical:
      research training and services), which uses validated tools to identify and to
      monitor the progress of patients who may benefit from psychological intervention.
      At outpatient clinics, patients used an electronic tablet to complete the General
      Anxiety Disorder Questionnaire (GAD-7), the Patient Health Questionnaire (PHQ-9),
      the Inclusion of Oral Health Impact Profile (OHIP-14), and the Brief Pain
      Inventory (BPI). Data were linked directly to their electronic record to allow
      the results, with suggestions for treatment, to be reviewed immediately during
      the consultation. A total of 162 patients were included. Screening showed that
      referral was required in 28 (17%) with a probable major depressive disorder and
      32 (20%) with a general anxiety disorder. Two (1%), who were identified as being
      at high risk of suicide or self-harm, were referred for immediate psychological
      assessment. Use of the system can aid the holistic treatment of patients with TMD
      through appropriate referral. Early identification of mental health problems and
      concurrent management are most beneficial in those who have had symptoms of TMD
      for up to two years, and are therefore essential.

PMID- 28457588
TI  - Mandibular wing osteotomy: technical modification.

PMID- 28457589
TI  - New method of arch bar fixation.

PMID- 28457590
TI  - Accuracy of maxillary repositioning by computer-aided orthognathic surgery in
      patients with normal temporomandibular joints.
AB  - Our aim was to assess the accuracy of computer-aided orthognathic surgery for
      maxillary repositioning in 15 patients with mandibular hyperplasia and normal
      temporomandibular joints (TMJ). We aligned preoperative and postoperative virtual
      skulls at the cranium using surface superimposition then recorded and calibrated
      three 3-dimensional coordinates (maxillary dental landmarks U0, 6R, and 6L) on
      the skulls. Errors between these preoperative and postoperative landmarks were
      calculated and the largest error of every patient was chosen for assessment.
      Landmark errors ranged from 1.00 - 2.49mm, and recording errors from -0.06 -
      0.07mm. The superimposition error was mean (SD) 0.036 (0.002)mm. The accuracy of
      the method is acceptable in patients with a normal TMJ.

PMID- 28457591
TI  - From mucolipidosis type IV to Ebola: TRPML and two-pore channels at the
      crossroads of endo-lysosomal trafficking and disease.
AB  - What do lysosomal storage disorders such as mucolipidosis type IV have in common
      with Ebola, cancer cell migration, or LDL-cholesterol trafficking? LDL
      cholesterol, certain bacterial toxins and viruses, growth factors, receptors,
      integrins, macromolecules destined for degradation or secretion are all sorted
      and transported via the endolysosomal system (ES). There are several pathways
      known in the ES, e.g. the degradation, the recycling, or the retrograde
      trafficking pathway. The ES comprises early and late endosomes, lysosomes and
      recycling endosomes as well as autophagosomes and lysosome related organelles.
      Contact sites between the ES and the endoplasmic reticulum or the Golgi apparatus
      may also be considered part of it. Dysfunction of this complex intracellular
      machinery can cause or contribute to the development of a number of diseases
      ranging from neurodegenerative, infectious, or metabolic diseases to retinal and
      pigmentation disorders as well as cancer and autophagy-related diseases.
      Endolysosomal ion channels such as mucolipins (TRPMLs) and two-pore channels
      (TPCs) play an important role in intracellular cation/calcium signaling and
      homeostasis and appear to critically contribute to the proper function of the
      endolysosomal trafficking network.

PMID- 28457592
TI  - Response to Letter to Editor on "Social impairments among children perinatally
      exposed to oxytocin or oxytocin receptor antagonist".

PMID- 28457593
TI  - A review of cutting mechanics and modeling techniques for biological materials.
AB  - This paper presents a comprehensive survey on the modeling of tissue cutting,
      including both soft tissue and bone cutting processes. In order to achieve higher
      accuracy in tissue cutting, as a critical process in surgical operations, the
      meticulous modeling of such processes is important in particular for surgical
      tool development and analysis. This review paper is focused on the mechanical
      concepts and modeling techniques utilized to simulate tissue cutting such as
      cutting forces and chip morphology. These models are presented in two major
      categories, namely soft tissue cutting and bone cutting. Fracture toughness is
      commonly used to describe tissue cutting while Johnson-Cook material model is
      often adopted for bone cutting in conjunction with finite element analysis (FEA).
      In each section, the most recent mathematical and computational models are
      summarized. The differences and similarities among these models, challenges,
      novel techniques, and recommendations for future work are discussed along with
      each section. This review is aimed to provide a broad and in-depth vision of the
      methods suitable for tissue and bone cutting simulations.

PMID- 28457594
TI  - IL-18 binding protein reverses the life-threatening hyperinflammation of a baby
      with the NLRC4 mutation.

PMID- 28457595
TI  - Mast cell-derived prostaglandin D2 attenuates anaphylactic reactions in mice.

PMID- 28457596
TI  - Homeostatic Plasticity Shapes Cell-Type-Specific Wiring in the Retina.
AB  - Convergent input from different presynaptic partners shapes the responses of
      postsynaptic neurons. Whether developing postsynaptic neurons establish
      connections with each presynaptic partner independently or balance inputs to
      attain specific responses is unclear. Retinal ganglion cells (RGCs) receive
      convergent input from bipolar cell types with different contrast responses and
      temporal tuning. Here, using optogenetic activation and pharmacogenetic
      silencing, we found that type 6 bipolar (B6) cells dominate excitatory input to
      ONalpha-RGCs. We generated mice in which B6 cells were selectively removed from
      developing circuits (B6-DTA). In B6-DTA mice, ONalpha-RGCs adjusted connectivity
      with other bipolar cells in a cell-type-specific manner. They recruited new
      partners, increased synapses with some existing partners, and maintained constant
      input from others. Patch-clamp recordings revealed that anatomical rewiring
      precisely preserved contrast and temporal frequency response functions of ONalpha
      RGCs, indicating that homeostatic plasticity shapes cell-type-specific wiring in
      the developing retina to stabilize visual information sent to the brain.

PMID- 28457597
TI  - Global epidemiology of non-influenza RNA respiratory viruses: data gaps and a
      growing need for surveillance.
AB  - Together with influenza, the non-influenza RNA respiratory viruses (NIRVs), which
      include respiratory syncytial virus, parainfluenza viruses, coronavirus,
      rhinovirus, and human metapneumovirus, represent a considerable global health
      burden, as recognised by WHO's Battle against Respiratory Viruses initiative. By
      contrast with influenza viruses, little is known about the contemporaneous global
      diversity of these viruses, and the relevance of such for development of
      pharmaceutical interventions. Although far less advanced than for influenza,
      antiviral drugs and vaccines are in different stages of development for several
      of these viruses, but no interventions have been licensed. This scarcity of
      global genetic data represents a substantial knowledge gap and impediment to the
      eventual licensing of new antiviral drugs and vaccines for NIRVs. Enhanced
      genetic surveillance will assist and boost research and development into new
      antiviral drugs and vaccines for these viruses. Additionally, understanding the
      global diversity of respiratory viruses is also part of emerging disease
      preparedness, because non-human coronaviruses and paramyxoviruses have been
      listed as priority concerns in a recent WHO research and development blueprint
      initiative for emerging infectious diseases. In this Personal View, we explain
      further the rationale for expanding the genetic database of NIRVs and emphasise
      the need for greater investment in this area of research.

PMID- 28457598
TI  - Genetic endowments, parental resources and adult health: Evidence from the Young
      Finns Study.
AB  - This paper uses longitudinal survey data linked to administrative registers to
      examine socioeconomic gradients in health, particularly whether the effects of
      genetic endowments interact with the socioeconomic resources of the parental
      household. We find that genetic risk scores contribute to adult health measured
      by biomarkers. This result is consistent with the findings from genome-wide
      association studies. Socioeconomic gradients in health differ based on biomarker
      and resource measures. Family education is negatively related to obesity and the
      waist-hip ratio, and family income is negatively related to low-density
      lipoprotein cholesterol and triglyceride levels. Parental resources do not modify
      the effects of genetic endowment on adult health. However, there is evidence for
      gene-family income interactions for triglyceride levels, particularly among
      women.

PMID- 28457599
TI  - Corkscrew Claw.
AB  - Corkscrew claw (CSC) is a conformational abnormality of the digit and affecting
      mostly but not exclusively the claws of the back leg, first reported during the
      1950s in Dutch black and white cattle. The affected claws are longer and narrower
      than the claw and have an inward and upward spiral rotation of the toe.
      Similarly, the bearing surface of the wall is displaced inward. The animal starts
      to bear weight on the abaxial wall surface, particularly the caudal segment, and
      the sole may become completely non-weight bearing. The axial wall is displaced
      dorsomedially and a fold develops in the wall.

PMID- 28457601
TI  - A new species of Diplocentrus (Scorpiones: Diplocentridae) with punctate pedipalp
      surfaces, a diagnostic character within the "mexicanus" group.
AB  - Diplocentrus duende n. sp. is described based on adult males collected from a
      locality in the Tehuacan-Cuicatlan Valley, Mexico. This species has punctate
      pedipalp surfaces, a condition present only in four other species of this
      specious genus. As suggested here, this condition has evolved independently in
      these species within the "mexicanus" group of Diplocentrus from the rest of the
      diplocentrids.

PMID- 28457602
TI  - Infectious diarrheal disease caused by contaminated well water in Chinese
      schools: A systematic review and meta-analysis.
AB  - BACKGROUND: In China, waterborne outbreaks of infectious diarrheal disease mainly
      occur in schools, and contaminated well water is a common source of pathogens.
      The objective of this review was to present the attack rates, durations of
      outbreak, pathogens of infectious diarrheal disease, and sanitary conditions of
      wells in primary and secondary schools in China, and to analyze risk factors and
      susceptibility of school children. METHODS: Relevant articles and reports were
      identified by searching PubMed, Web of Science, China National Knowledge
      Infrastructure, China Information System for Disease Control and Prevention, and
      the Chinese Field Epidemiology Training Program. Essential information, including
      urban/rural areas, school types, attack rates, pathogens, durations of outbreak,
      report intervals, and interventions were extracted from the eligible articles.
      Wilcoxon signed-rank test, Kruskal-Wallis H test, and Spearman correlation test
      were conducted in statistical analyses. Sex- and age-specific attack rate ratios
      were calculated as pooled effect sizes. RESULTS: We screened 2188 articles and
      retrieved data of 85 outbreaks from 1987 to 2014. Attack rates of outbreaks in
      rural areas (median, 12.63 cases/100 persons) and in primary schools (median,
      14.54 cases/100 persons) were higher than those in urban areas (median, 5.62
      cases/100 persons) and in secondary schools (median, 8.74 cases/100 persons) (P =
      0.004 and P = 0.013, respectively). Shigella, pathogenic Escherichia coli, and
      norovirus were the most common pathogens. Boys tended toward higher attack rates
      than girls (sex-specific attack rate ratio, 1.13; 95% CI, 1.00-1.29, P = 0.05).
      Unsanitary conditions of water wells were reported frequently, and unhealthy
      behavior habits were common in students. CONCLUSION: School children were
      susceptible to waterborne disease in China. Chinese government should make
      efforts to improve access to safe water in schools. Health education promotion
      and conscientiousness of school leaders and teachers should be enhanced.

PMID- 28457603
TI  - Healthy and diseased coronary bifurcation geometries influence near-wall and
      intravascular flow: A computational exploration of the hemodynamic risk.
AB  - Local hemodynamics has been identified as one main determinant in the onset and
      progression of atherosclerotic lesions at coronary bifurcations. Starting from
      the observation that atherosensitive hemodynamic conditions in arterial
      bifurcation are majorly determined by the underlying anatomy, the aim of the
      present study is to investigate how peculiar coronary bifurcation anatomical
      features influence near-wall and intravascular flow patterns. Different
      bifurcation angles and cardiac curvatures were varied in population-based,
      idealized models of both stenosed and unstenosed bifurcations, representing the
      left anterior descending (LAD) coronary artery with its diagonal branch. Local
      hemodynamics was analyzed in terms of helical flow and exposure to
      low/oscillatory shear stress by performing computational fluid dynamics
      simulations. Results show that bifurcation angle impacts lowly hemodynamics in
      both stenosed and unstenosed cases. Instead, curvature radius influences the
      generation and transport of helical flow structures, with smaller cardiac
      curvature radius associated to higher helicity intensity. Stenosed bifurcation
      models exhibit helicity intensity values one order of magnitude higher than the
      corresponding unstenosed cases. Cardiac curvature radius moderately affects near
      wall hemodynamics of the stenosed cases, with smaller curvature radius leading to
      higher exposure to low shear stress and lower exposure to oscillatory shear
      stress. In conclusion, the proposed controlled benchmark allows investigating the
      effect of various geometrical features on local hemodynamics at the LAD/diagonal
      bifurcation, highlighting that cardiac curvature influences near wall and
      intravascular hemodynamics, while bifurcation angle has a minor effect.

PMID- 28457604
TI  - Local displacement and strain uncertainties in different bone types by digital
      volume correlation of synchrotron microtomograms.
AB  - Understanding bone mechanics at different hierarchical levels is fundamental to
      improve preclinical and clinical assessments of bone strength. Digital Volume
      Correlation (DVC) is the only experimental measurement technique used for
      measuring local displacements and calculating local strains within bones. To
      date, its combination with laboratory source micro-computed tomography (LS
      microCT) data typically leads to high uncertainties, which limit its application.
      Here, the benefits of synchrotron radiation micro-computed tomography (SR
      microCT) for DVC are reported. Specimens of cortical and trabecular bovine bone
      and murine tibiae, were each scanned under zero-strain conditions with an
      effective voxel size of 1.6MUm. In order to consider the effect of the voxel
      size, analyses were also performed on downsampled images with voxel size of 8MUm.
      To evaluate displacement and strain uncertainties, each pair of tomograms was
      correlated using a global DVC algorithm (ShIRT-FE). Displacement random errors
      for original SR-microCT ranged from 0.024 to 0.226MUm, depending on DVC nodal
      spacing. Standard deviation of strain errors was below 200 microstrain (ca. 1/10
      of the strain associated with physiological loads) for correlations performed
      with a measurement spatial resolution better than 40MUm for cortical bovine bone
      (240MUm for downsampled images), 80MUm for trabecular bovine bone (320MUm for
      downsampled images) and murine tibiae (120MUm for downsampled images). This study
      shows that the uncertainties of SR-microCT-based DVC, estimated from repeated
      scans, are lower than those obtained from LS-microCT-based DVC on similar
      specimens and low enough to measure accurately the local deformation at the
      tissue level.

PMID- 28457600
TI  - Fatty acid transporting proteins: Roles in brain development, aging, and stroke.
AB  - Polyunsaturated fatty acids are required for the brain development and
      significantly impact aging and stroke. Due to the hydrophobicity of fatty acids,
      fatty acids transportation related proteins that include fatty acid binding
      proteins (FABPs), long chain acyl-coA synthase (ACS), fatty acid transportation
      proteins (FATPs), fatty acid translocase (FAT/CD36) and newly reported major
      facilitator superfamily domain-containing protein (Mfsd2a) play critical roles in
      the uptake of various fatty acids, especially polyunsaturated fatty acids. They
      are not only involved in neurodevelopment, but also have great impact on
      neurological disease, such as aging related dementia and stroke.

PMID- 28457605
TI  - The effects of morphological irregularity on the mechanical behavior of
      interdigitated biological sutures under tension.
AB  - Irregular interdigitated morphology is prevalent in biological sutures in nature.
      Suture complexity index has long been recognized as the most important
      morphological parameter to govern the mechanical properties of biological
      sutures. However, the suture complexity index alone does not reflect all aspects
      of suture morphology. The goal of this investigation was to determine that
      besides suture complexity index, whether the degree of morphological irregularity
      of biological sutures has influences on the mechanical properties, and if there
      is any, how to quantify these influences. To explore these issues, theoretical
      and finite element (FE) suture models with the same suture complexity index but
      different levels of morphological irregularity were developed. The quasi-static
      stiffness, strength for damage initiation and post-failure process of irregular
      sutures were studied. It was shown that for the same suture complexity index,
      when the level of morphological irregularity increases, the overall strain to
      failure will increase while tensile stiffness is retained; also, the total energy
      to fracture increases with a sacrifice in strength to damage initiation. These
      results reveal that morphological irregularity is another important independent
      parameter to govern and balance the mechanical properties of biological sutures.
      Therefore, from the mechanics point of view, the prevalence of irregular suture
      morphology in nature is a merit, not a defect.

PMID- 28457606
TI  - Combined measurement and modeling of specimen-specific knee mechanics for healthy
      and ACL-deficient conditions.
AB  - Quantifying the mechanical environment at the knee is crucial for developing
      successful rehabilitation and surgical protocols. Computational models have been
      developed to complement in vitro studies, but are typically created to represent
      healthy conditions, and may not be useful in modeling pathology and repair. Thus,
      the objective of this study was to create finite element (FE) models of the
      natural knee, including specimen-specific tibiofemoral (TF) and patellofemoral
      (PF) soft tissue structures, and to evaluate joint mechanics in intact and ACL
      deficient conditions. Simulated gait in a whole joint knee simulator was
      performed on two cadaveric specimens in an intact state and subsequently repeated
      following ACL resection. Simulated gait was performed using motor-actuated
      quadriceps, and loads at the hip and ankle. Specimen-specific FE models of these
      experiments were developed in both intact and ACL-deficient states. Model
      simulations compared kinematics and loading of the experimental TF and PF joints,
      with average RMS differences [max] of 3.0 degrees  [8.2 degrees ] and 2.1 degrees
      [8.4 degrees ] in rotations, and 1.7 [3.0] and 2.5 [5.1] mm in translations, for
      intact and ACL-deficient states, respectively. The timing of peak quadriceps
      force during stance and swing phase of gait was accurately replicated within 2
      degrees  of knee flexion and with an average error of 16.7% across specimens and
      pathology. Ligament recruitment patterns were unique in each specimen;
      recruitment variability was likely influenced by variations in ligament
      attachment locations. ACL resections demonstrated contrasting joint mechanics in
      the two specimens with altered knee motion shown in one specimen (up to 5mm
      anterior tibial translation) while increased TF joint loading was shown in the
      other (up to 400N).

PMID- 28457607
TI  - Erratum to "Frequent methylation and oncogenic role of microRNA-34b/c in small
      cell lung cancer" [Lung Cancer 76 (1) (2012) 32-38].

PMID- 28457608
TI  - Corrigendum to "Prognosis in advanced lung cancer - A prospective study examining
      key clinicopathological factors" [Lung Cancer 88 (2015) 304-309].

PMID- 28457609
TI  - Cryo-EM Structure of a Relaxase Reveals the Molecular Basis of DNA Unwinding
      during Bacterial Conjugation.
AB  - Relaxases play essential roles in conjugation, the main process by which bacteria
      exchange genetic material, notably antibiotic resistance genes. They are
      bifunctional enzymes containing a trans-esterase activity, which is responsible
      for nicking the DNA strand to be transferred and for covalent attachment to the
      resulting 5'-phosphate end, and a helicase activity, which is responsible for
      unwinding the DNA while it is being transported to a recipient cell. Here we show
      that these two activities are carried out by two conformers that can both load
      simultaneously on the origin of transfer DNA. We solve the structure of one of
      these conformers by cryo electron microscopy to near-atomic resolution,
      elucidating the molecular basis of helicase function by relaxases and revealing
      insights into the mechanistic events taking place in the cell prior to substrate
      transport during conjugation.

PMID- 28457611
TI  - Pros and Cons of Red Blood Cell Transfusion in Extremely Low Birth Weight
      Infants.

PMID- 28457610
TI  - Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus
      Monkeys.
AB  - Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as
      Guillain-Barre syndrome and other neurologic disorders in adults. Prolonged viral
      shedding has been reported in semen, suggesting the presence of anatomic viral
      reservoirs. Here we show that ZIKV can persist in cerebrospinal fluid (CSF) and
      lymph nodes (LN) of infected rhesus monkeys for weeks after virus has been
      cleared from peripheral blood, urine, and mucosal secretions. ZIKV-specific
      neutralizing antibodies correlated with rapid clearance of virus in peripheral
      blood but remained undetectable in CSF for the duration of the study. Viral
      persistence in both CSF and LN correlated with upregulation of mechanistic target
      of rapamycin (mTOR), proinflammatory, and anti-apoptotic signaling pathways, as
      well as downregulation of extracellular matrix signaling pathways. These data
      raise the possibility that persistent or occult neurologic and lymphoid disease
      may occur following clearance of peripheral virus in ZIKV-infected individuals.

PMID- 28457612
TI  - Editorial commentary: Improving our understanding of type 2 myocardial infarction
      and myocardial injury.

PMID- 28457613
TI  - Flanged Intrascleral Intraocular Lens Fixation with Double-Needle Technique.
AB  - PURPOSE: To report the clinical outcomes of a new technique for transconjunctival
      intrascleral fixation of an intraocular lens (IOL). DESIGN: Prospective,
      noncomparative, interventional case series. PARTICIPANTS: One hundred eyes of 97
      consecutive patients with aphakia, dislocated IOL, or subluxated crystalline lens
      who underwent posterior chamber sutureless implantation of an IOL were studied.
      METHODS: Two angled incisions parallel to the limbus were made by 30-gauge thin
      wall needles. Haptics of an IOL were externalized with the needles and cauterized
      to make a flange of the haptics. The flange of the haptics were pushed back and
      fixed into the scleral tunnels. MAIN OUTCOME MEASURES: Best-corrected visual
      acuity (VA), corneal endothelial cell density, IOL tilt, and complications were
      determined. RESULTS: The IOLs were fixed with exact centration and axial
      stability. The mean preoperative best-corrected VA was 0.25 logarithm of the
      minimum angle of resolution (logMAR) units; after surgery, it improved
      significantly to 0.11 logMAR, 0.09 logMAR, 0.12 logMAR, and 0.04 logMAR at 6, 12,
      24, and 36 months, respectively (P < 0.01, P < 0.01, P = 0.03, and P = 0.10,
      respectively). The mean corneal endothelial cell density decreased from 2341
      cells/mm2 before surgery to 2313 cells/mm2, 2240 cells/mm2, 2189 cells/mm2, and
      2244 cells/mm2 at 6, 12, 24, and 36 months, respectively (P < 0.01, P < 0.01, P <
      0.01, and P = 0.17, respectively). The mean IOL tilt was 3.4 degrees +/-2.5
      degrees . The postoperative complications included iris capture by the IOL in 8
      eyes (8%), vitreous hemorrhage in 5 eyes (5%), and cystoid macular edema in 1 eye
      (1%). There were no incidents of postoperative retinal detachment,
      endophthalmitis, or IOL dislocation. CONCLUSIONS: We have developed a new
      technique for intrascleral IOL fixation. The flanged IOL fixation technique is a
      simple and minimally invasive method for achieving good IOL fixation with firm
      haptic fixation.

PMID- 28457614
TI  - Corneal Collagen Cross-Linking in the Management of Keratoconus in Canada: A Cost
      Effectiveness Analysis.
AB  - PURPOSE: To use patient-level microsimulation models to evaluate the comparative
      cost-effectiveness of early corneal cross-linking (CXL) and conventional
      management with penetrating keratoplasty (PKP) when indicated in managing
      keratoconus in Canada. DESIGN: Cost-utility analysis using individual-based,
      state-transition microsimulation models. PARTICIPANTS: Simulated cohorts of 100
      000 individuals with keratoconus who entered each treatment arm at 25 years of
      age. Fellow eyes were modeled separately. Simulated individuals lived up to a
      maximum of 110 years. METHODS: We developed 2 state-transition microsimulation
      models to reflect the natural history of keratoconus progression and the impact
      of conventional management with PKP versus CXL. We collected data from the
      published literature to inform model parameters. We used realistic parameters
      that maximized the potential costs and complications of CXL, while minimizing
      those associated with PKP. In each treatment arm, we allowed simulated
      individuals to move through health states in monthly cycles from diagnosis until
      death. MAIN OUTCOME MEASURES: For each treatment strategy, we calculated the
      total cost and number of quality-adjusted life years (QALYs) gained. Costs were
      measured in Canadian dollars. Costs and QALYs were discounted at 5%, converting
      future costs and QALYs into present values. We used an incremental cost
      effectiveness ratio (ICER = difference in lifetime costs/difference in lifetime
      health outcomes) to compare the cost-effectiveness of CXL versus conventional
      management with PKP. RESULTS: Lifetime costs and QALYs for CXL were estimated to
      be Can$5530 (Can$4512, discounted) and 50.12 QALYs (16.42 QALYs, discounted).
      Lifetime costs and QALYs for conventional management with PKP were Can$2675
      (Can$1508, discounted) and 48.93 QALYs (16.09 QALYs, discounted). The discounted
      ICER comparing CXL to conventional management was Can$9090/QALY gained.
      Sensitivity analyses revealed that in general, parameter variations did not
      influence the cost-effectiveness of CXL. CONCLUSIONS: CXL is cost-effective
      compared with conventional management with PKP in the treatment of keratoconus.
      Our ICER of Can$9090/QALY falls well below the range of Can$20 000 to Can$100
      000/QALY and below US$50 000/QALY, thresholds generally used to evaluate the cost
      effectiveness of health interventions in Canada and the United States. This study
      provides strong economic evidence for the cost-effectiveness of early CXL in
      keratoconus.

PMID- 28457615
TI  - The effect of pressure and shear on tissue viability of human skin in relation to
      the development of pressure ulcers: a systematic review.
AB  - Pressure ulcers are a significant problem in health care, due to high costs and
      large impact on patients' life. In general, pressure ulcers develop as tissue
      viability decreases due to prolonged mechanical loading. The relation between
      load and tissue viability is highly influenced by individual characteristics. It
      is proposed that measurements of skin blood flow regulation could provide good
      assessment of the risk for pressure ulcer development, as skin blood flow is
      essential for tissue viability. . Therefore, the aim of this systematic review is
      to gain insight in the relation between mechanical load and the response of the
      skin and underlying tissue to this loading measured in-vivo with non-invasive
      techniques. A systematic literature search was performed to identify articles
      analysing the relation between mechanical load (pressure and/or shear) and tissue
      viability measured in-vivo. Two independent reviewers scored the methodological
      quality of the 22 included studies. Methodological information as well as tissue
      viability parameters during load application and after load removal were
      extracted from the included articles and used in a meta-analysis. Pressure
      results in a decrease in skin blood flow parameters, compared to baseline;
      showing a larger decrease with higher magnitudes of load. The steepness of the
      decrease is mostly dependent on the anatomical location. After load removal the
      magnitude of the post-reactive hyperaemic peak is related to the magnitude of
      pressure. Lastly, shear in addition to pressure, shows an additional negative
      effect, but the effect is less apparent than pressure on skin viability.

PMID- 28457616
TI  - Corrigendum to "Radiation Dosage for Percutaneous PAD Treatment is Different in
      Cardiovascular Disciplines: Results From an Eleven Year Population Based Registry
      in the Metropolitan Area of Hamburg" [Eur J Vasc Endovasc Surg 53 (2016) 215
      222].

PMID- 28457617
TI  - Metabolomics reveals intratumor heterogeneity - Implications for precision
      medicine.

PMID- 28457618
TI  - Are SIRT1 activators another indirect method to increase AMPK for beneficial
      effects on aging and the metabolic syndrome?

PMID- 28457619
TI  - Borrelia burgdorferi-specific IgA in Lyme Disease.
AB  - The laboratory diagnosis of Lyme disease is currently dependent on the detection
      of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of
      the disease. The significance of serum IgA against B. burgdorferi remains
      unclear. The production of intrathecal IgA has been noted in patients with the
      late Lyme disease manifestation, neuroborreliosis, but production of antigen
      specific IgA during early disease has not been evaluated. In the current study,
      we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the
      target of the FDA-cleared C6 EIA, and FlaB(211-223)-modVlsE(275-291), a peptide
      containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in
      patients with early and late Lyme disease. Specific IgA was detected in 59 of 152
      serum samples (38.8%) from early Lyme disease patients. Approximately 50% of
      early Lyme disease patients who were seropositive for peptide-specific IgM and/or
      IgG were also seropositive for peptide-specific IgA. In a subpopulation of
      patients, high peptide-specific IgA could be correlated with disseminated
      disease, defined as multiple erythema migrans lesions, and neurological disease
      complications. These results suggest that there may be an association between
      elevated levels of antigen-specific IgA and particular disease manifestations in
      some patients with early Lyme disease.

PMID- 28457620
TI  - Perfusion Deficits and Association with Clinical Outcome in Patients with
      Anterior Choroidal Artery Stroke.
AB  - BACKGROUND AND PURPOSE: Anterior choroidal artery (AChA) strokes have a varied
      pattern of tissue injury, prognosis, and clinical outcome. It is unclear whether
      perfusion deficit in AChA stroke is associated with the clinical outcome. This
      study aims to determine the frequency of perfusion abnormalities in AChA stroke
      and association with clinical outcome. METHODS: The study cohort was derived from
      ischemic stroke patients admitted to 2 stroke centers between July 2001 and July
      2014. All patients received an acute magnetic resonance imaging (MRI) scan.
      Patients with ischemic stroke restricted to the AChA territory were included in
      the study. Lesion size was measured as the largest diameter on diffusion-weighted
      imaging (DWI) or apparent diffusion coefficient and divided into 2 groups (<20 mm
      or >=20 mm). Group comparisons were performed among patients with and without
      perfusion abnormalities and based on diffusion diameter. Favorable clinical
      outcome was defined as discharge to home. RESULTS: A total of 120 patients were
      included in the study. Perfusion deficits were identified in 67% of patients. The
      admission National Institutes of Health Stroke Scale (NIHSS) was higher in
      patients with perfusion abnormalities (P = .027). Diameter lesion size on DWI was
      larger among patients with a perfusion deficit median [interquartile range], 1.63
      [1.3-2.0], as compared with those without, 1.18 [1.0-1.7], P < .0001. Patients
      with a perfusion deficit were less likely to be discharged to home than those
      without (36% versus 60%, P = .013). CONCLUSIONS: Two thirds of patients with an
      AChA stroke have a perfusion deficit on MRI, higher admission NIHSS, and larger
      DWI lesion size at presentation.

PMID- 28457621
TI  - Validation of the National Institutes of Health Stroke Scale-8 to Detect Large
      Vessel Occlusion in Ischemic Stroke.
AB  - BACKGROUND: Patients with acute ischemic stroke and large vessel occlusion (LVO)
      may benefit from prehospital identification and transfer to a center offering
      endovascular therapy. AIMS: We aimed to assess the accuracy of an existing 8-item
      stroke scale (National Institutes of Health Stroke Scale-8 [NIHSS-8]) for
      identification of patients with acute stroke with LVO. METHODS: We
      retrospectively calculated NIHSS-8 scores in a population of consecutive patients
      with presumed acute stroke assessed by emergency medical services (EMS). LVO was
      identified on admission computed tomography angiography. Accuracy to identify LVO
      was calculated using receiver operating characteristics analysis. We used
      weighted Cohen's kappa statistics to assess inter-rater reliability for the NIHSS
      8 score between the EMS and the hospital stroke team on a prospectively evaluated
      subgroup. RESULTS: Of the 551 included patients, 381 had a confirmed ischemic
      stroke and 136 patients had an LVO. NIHSS scores were significantly higher in
      patients with LVO (median 18; interquartile range 14-22). The NIHSS-8 score
      reliably predicted the presence of LVO (area under the receiver operating
      characteristic curve .82). The optimum NIHSS-8 cutoff of 8 or more had a
      sensitivity of .81, specificity of .75, and Youden index of .56 for prediction of
      LVO. The EMS and the stroke team reached substantial agreement (kappa = .69).
      CONCLUSIONS: Accuracy of the NIHSS-8 to identify LVO in a population of patients
      with suspected acute stroke is comparable to existing prehospital stroke scales.
      The scale can be performed by EMS with reasonable reliability. Further validation
      in the field is needed to assess accuracy of the scale to identify patients with
      LVO eligible for endovascular treatment in a prehospital setting.

PMID- 28457622
TI  - [Is MRI useful in the follow-up of pyogenic vertebral osteomyelitis?]

PMID- 28457623
TI  - [A persistent "conjunctivitis" in a 2-year-old boy].

PMID- 28457624
TI  - High miR-124-3p expression identifies smoking individuals susceptible to
      atherosclerosis.
AB  - BACKGROUND AND AIMS: The risk of developing cardiovascular disease (CVD) is twice
      as high among smoking individuals compared to non-smokers. Monocytes are involved
      in smoking-related atherosclerotic plaque formation. In this study, we
      investigated whether smokers with an increased risk of developing CVD can be
      identified on the basis of monocyte-derived miRNA expression levels. METHODS: We
      performed a miRNA microarray experiment on isolated monocytes from smoking,
      former smoking and non-smoking individuals in a cohort of patients with premature
      CVD and healthy controls (Cohort I, n = 76). RESULTS: We found miR-124-3p to be
      heterogeneously expressed among all smoking individuals, whereas expression was
      low in non-smokers. Subsequently, RT-qPCR measurements on whole blood showed that
      among smoking individuals an increase in miR-124-3p is associated with an
      increased risk for advanced atherosclerotic disease (cohort II, n = 24) (OR 11.72
      95% CI 1.09-126.53) and subclinical atherosclerosis (coronary artery calcium
      score >= 80th percentile, cohort III n = 138) (OR 2.71, 95% CI 1.05-7.01). This
      was not observed among former smokers or non-smoking individuals. Flow cytometric
      analysis demonstrated that high miR-124-3p expression was associated with
      upregulation of the monocyte surface markers CD45RA, CD29 and CD206, indicating
      an altered monocyte phenotype. Finally, overexpression of miR-124-3p resulted in
      an upregulation of CD206 surface expression on monocytes. CONCLUSIONS: High miR
      124-3p expression is associated with an increased risk of subclinical
      atherosclerosis in smoking individuals and with an altered monocyte phenotype.
      This may suggest that miR-124-3p identifies which smoking individuals are
      susceptible to the atherogenic effects of smoking.

PMID- 28457625
TI  - Effects of atorvastatin and diet interventions on atherosclerotic plaque
      inflammation and [18F]FDG uptake in Ldlr-/-Apob100/100 mice.
AB  - BACKGROUND AND AIMS: Uptake of the positron emission tomography (PET) tracer 2
      deoxy-2-[18F]-fluoro-d- glucose ([18F]FDG) into macrophages is a sensitive marker
      of inflammation in atherosclerosis. To assess the anti-inflammatory effects of
      statins, we studied whether atorvastatin therapy reduces aortic [18F]FDG uptake
      in hypercholesterolemic mice deficient in low-density lipoprotein receptor
      (Ldlr), and expressing only apolipoprotein B-100 (Ldlr-/-Apob100/100). METHODS:
      Thirty-six Ldlr-/-Apob100/100 mice were fed a high-fat diet (HFD) for 12 weeks
      and then allocated to receive a HFD (n = 13), chow diet (Chow, n = 12), or HFD
      with added atorvastatin (HFD + A, n = 11), for another 12 weeks. In addition to
      aortic histopathology, [18F]FDG uptake was studied in vivo using PET/computed
      tomography (CT), and ex vivo by gamma counting of excised aorta. RESULTS: Total
      cholesterol levels were lower in the Chow and HFD + A groups than in the HFD
      group (10 +/- 3.2, 23 +/- 4.9 and 34 +/- 9.2 mmol/l, respectively), with the Chow
      group also showing a lower plaque burden and lower numbers of macrophages in the
      lesions. Compared to the HFD group, [18F]FDG uptake in the aorta (normalized for
      blood) was lower in the Chow group in both in vivo (2.1 +/- 0.21 vs. 1.7 +/-
      0.25, p = 0.018) and ex vivo (5.2 +/- 2.3 vs. 2.8 +/- 0.87, p = 0.011) analyses,
      whereas atorvastatin had no effect on uptake (2.1 +/- 0.42 in vivo and 3.9 +/-
      1.8 ex vivo). [18F]FDG uptake correlated with plasma total cholesterol levels.
      CONCLUSIONS: Atorvastatin therapy did not show cholesterol-independent effects on
      inflammation in atherosclerotic lesions in Ldlr-/-Apob100/100 mice, as determined
      by histology and [18F]FDG PET, whereas a cholesterol-lowering diet intervention
      was effective.

PMID- 28457626
TI  - Open letter to WHO DG candidates: keep policy and priority setting free of
      commercial influence.

PMID- 28457627
TI  - Department of Error.

PMID- 28457628
TI  - 10 vs 5 years of adjuvant tamoxifen: exclusion of 1/402 centres in ATLAS.

PMID- 28457629
TI  - Mosaicism in Preimplantation Human Embryos: When Chromosomal Abnormalities Are
      the Norm.
AB  - Along with errors in meiosis, mitotic errors during post-zygotic cell division
      contribute to pervasive aneuploidy in human embryos. Relatively little is known,
      however, about the genesis of these errors or their fitness consequences. Rapid
      technological advances are helping to close this gap, revealing diverse molecular
      mechanisms contributing to mitotic error. These include altered cell cycle
      checkpoints, aberrations of the centrosome, and failed chromatid cohesion,
      mirroring findings from cancer biology. Recent studies are challenging the idea
      that mitotic error is abnormal, emphasizing that the fitness impacts of mosaicism
      depend on its scope and severity. In light of these findings, technical and
      philosophical limitations of various screening approaches are discussed, along
      with avenues for future research.

PMID- 28457630
TI  - Non-Invasive Thrombolysis Using Microtripsy in a Porcine Deep Vein Thrombosis
      Model.
AB  - Histotripsy is a non-invasive therapeutic technique that uses ultrasound
      generated from outside the body to create controlled cavitation in targeted
      tissue, and fractionates it into acellular debris. We have developed a new
      histotripsy approach, termed microtripsy, to improve targeting accuracy and to
      avoid collateral tissue damage. This in vivo study evaluates the safety and
      efficacy of microtripsy for non-invasive thrombolysis in a porcine deep vein
      thrombosis model. Acute thrombi were formed in left femoral veins of pigs (~35
      kg) by occluding the vessel using two balloon catheters and infusing with
      thrombin. Guided by real-time ultrasound imaging, microtripsy thrombolysis
      treatment was conducted in 14 pigs; 10 pigs were euthanized on the same day
      (acute) and 4 at 2 wk (subacute). To evaluate vessel damage, 30-min free-flow
      treatment in the right femoral vein (no thrombus) was also conducted in 8 acute
      pigs. Blood flow was successfully restored or significantly increased after
      treatment in 13 of the 14 pigs. The flow channels re-opened by microtripsy had a
      diameter up to 64% of the vessel diameter (~6 mm). The average treatment time was
      16 min per centimeter-long thrombus. Only mild intravascular hemolysis was
      induced during microtripsy thrombolysis. No damage was observed on vessel walls
      after 2 wk of recovery, venous valves were preserved, and there was no sign of
      pulmonary embolism. The results of this study indicate that microtripsy has the
      potential to be a safe and effective treatment for deep vein thrombosis in a
      porcine model.

PMID- 28457631
TI  - Quantitative Assessment of Skin Stiffness in Localized Scleroderma Using
      Ultrasound Shear-Wave Elastography.
AB  - The purpose of this study was to evaluate the usefulness of ultrasound shear-wave
      elastography (US-SWE) in characterization of localized scleroderma (LS), as well
      as in the disease staging. A total of 21 patients with 37 LS lesions were
      enrolled in this study. The pathologic stage (edema, sclerosis or atrophy) of the
      lesions was characterized by pathologic examination. The skin elastic modulus (E
      values including Emean, Emin, Emax and Esd) and thickness (h) was evaluated both
      in LS lesions and site-matched unaffected skin (normal controls) using US-SWE.
      The relative difference of E-values (ERD) was calculated between each pair of
      lesions and its normal control for comparison among different pathologic stages.
      Of the 37 LS lesions, 2 were in edema, 22 were in sclerosis and 13 were in
      atrophy. US-SWE results showed a significant increase of skin elastic modulus and
      thickness in all lesions (p < 0.001 in sclerosis and p < 0.05 in atrophy)
      compared with the normal controls. The measured skin elastic modulus and
      thickness were greater in sclerosis than in atrophy. However, once normalized by
      skin thickness, the atrophic lesions, which were on average thinner, appeared
      significantly stiffer than those of the sclerosis (normalized ERD: an increase of
      316.3% in atrophy vs. 50.6% in sclerosis compared with the controls, p = 0.007).
      These findings suggest that US-SWE allows for quantitative evaluation of the skin
      stiffness of LS lesions in different stages; however, the E-values directly
      provided by the US-SWE system alone do not distinguish between the stages, and
      the normalization by skin thickness is necessary. This non-invasive, real-time
      imaging technique is an ideal tool for assessing and monitoring LS disease
      severity and progression.

PMID- 28457632
TI  - Low-Intensity Pulsed Ultrasound-Induced Spinal Fusion is Coupled with Enhanced
      Calcitonin Gene-Related Peptide Expression in Rat Model.
AB  - Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate fracture
      healing. In this study, we analyzed the role of calcitonin gene-related peptide
      (CGRP) in a rat spinal fusion model treated with LIPUS. The results revealed that
      LIPUS significantly increases bone formation, and the process was coupled with
      elevated CGRP innervation. CGRP was located in fibrous tissue, closely
      surrounding the allograft and newly formed cartilage. The density of CGRP peaked
      at week 3 after surgery in both the control (non-LIPUS-treated) and LIPUS-treated
      groups. These results suggest that LIPUS might accelerate spinal fusion by
      promoting sensory nerve fiber innervation.

PMID- 28457633
TI  - Effect of Post Space Preparation on Apical Obturation Quality of Teeth Obturated
      with Different Techniques: A Micro-computed Tomographic Study.
AB  - INTRODUCTION: The purpose of this study was to evaluate the obturation quality of
      root canals filled with different techniques and to determine whether post space
      preparation had an effect on the quality of apical obturation using micro
      computed tomographic (micro-CT) imaging. METHODS: The root canals of 30 human
      mandibular premolar teeth were instrumented, and the specimens were divided into
      3 groups according to the obturation technique used: cold lateral compaction
      (CLC), warm vertical compaction (WVC), or single-cone (SC) techniques. The
      specimens were stored at 37 degrees C and 100% humidity for 1 week. Then, the
      coronal root filling material was removed in order to create a post space. Micro
      CT scans were performed before and after post space preparation for the
      volumetric analysis of voids and filling materials. Data were analyzed using
      repeated-measures analysis of variance and Bonferroni tests. RESULTS: The CLC and
      SC groups showed a significantly greater percentage volume of voids than the WVC
      group (P < .05), whereas no significant difference was found between the CLC and
      SC groups before and after post space preparation (P > .05). The post space
      preparation caused a significant increase in the percentage volume of voids in
      the CLC and SC groups (P < .05). No significant difference was detected in the
      percentage volume of voids in the WVC group after post space preparation (P >
      .05). CONCLUSIONS: No root fillings were void free. The WVC group presented the
      best obturation quality. The post space preparation negatively influenced the
      apical integrity of the filling materials in the CLC and SC groups, whereas it
      had no significant effect in the WVC group.

PMID- 28457634
TI  - Combined Effects of Vascular Endothelial Growth Factor and Bone Morphogenetic
      Protein 2 on Odonto/Osteogenic Differentiation of Human Dental Pulp Stem Cells In
      Vitro.
AB  - INTRODUCTION: The purpose of this study was to investigate whether combined and
      concerted delivery of vascular endothelial growth factor (VEGF) and bone
      morphogenetic protein 2 (BMP-2) enhances odonto/osteogenic differentiation of
      human dental pulp stem cells (DPSCs) in vitro. METHODS: Various concentrations of
      VEGF and/or BMP-2 with or without the presence of odonto/osteogenic medium (OM)
      were added into DPSC cultures for 21 days. The mineral formation in cultures was
      evaluated using alizarin red stain (ARS). Optimal concentrations of VEGF and BMP
      2 were codelivered to DPSCs for total of 21 days with the following experimental
      groups: (1) group 1: OM only, (2) group 2: OM + VEGF, (3) group 3: OM + BMP-2,
      and (4) group 4: OM + VEGF + BMP-2 (subgroup 4a: VEGF present the first 7 days,
      4b: BMP-2 present the last 14 days, and 4c, both present for 21 days). Cultures
      were then subjected to quantitative ARS analysis or harvested for quantitative
      polymerase chain reaction analysis for the expression of core-binding factor
      alpha 1 (CBFA1), alkaline phosphatase (ALP), and dentin matrix protein 1 (DMP-1).
      RESULTS: No mineral formation was detected by ARS when VEGF and/or BMP-2 were
      used without OM. OM + VEGF, but not OM + BMP-2, formed more mineralization than
      OM (P < .05). In the codelivery groups, the highest mineralization was observed
      in OM + VEGF and subgroup 4a compared with OM or the other groups (P < .05).
      Quantitative polymerase chain reaction analysis showed that CBFA1, ALP, and DMP-1
      levels were higher in groups 2, 3, and 4a compared with 4b and 4c (P < .05).
      CBFA1 expressed higher in groups 2, 3, and 4a compared with OM (P < .05). For ALP
      expression, only subgroup 4a expressed higher than OM (P < .05). No difference
      was detected between groups 2 and 3 (P > .05) in the expression of the 3 genes.
      CONCLUSIONS: VEGF addition in the early phase rather than a continuous presence
      of both VEGF and BMP-2 enhances odonto/osteogenic differentiation of DPSCs.

PMID- 28457635
TI  - High-purity Nisin Alone or in Combination with Sodium Hypochlorite Is Effective
      against Planktonic and Biofilm Populations of Enterococcus faecalis.
AB  - INTRODUCTION: Nisin, a broad-spectrum bacteriocin, has recently been highlighted
      for its biomedical applications. To date, no studies have examined the
      antimicrobial and antibiofilm properties of high-purity (>95%) nisin (nisin ZP)
      on Enterococcus faecalis and biofilms formed by this species. We hypothesize that
      nisin can inhibit E. faecalis and reduce biofilm biomass, and combinations of
      nisin and sodium hypochlorite (NaOCl) will enhance the antibiofilm properties
      against E. faecalis biofilms. METHODS: Using broth cultures, disc diffusion
      assays, and biofilm assays, we examined the effects of nisin on various E.
      faecalis growth parameters and biofilm properties (biovolume, thickness, and
      roughness). Confocal microscopy was used in conjunction with Imaris and Comstat2
      software (Kongens Lyngby, Copenhagen, Denmark) to measure and analyze the biofilm
      properties. RESULTS: Nisin significantly decreased the growth of planktonic E.
      faecalis dose dependently. The minimum inhibitory concentrations against E.
      faecalis strains OG-1 and ATCC 29212 were 15 and 50 MUg/mL, and the minimum
      bactericidal concentrations were 150 and 200 MUg/mL, respectively. A reduction in
      biofilm biovolume and thickness was observed for biofilms treated with nisin at
      >=10 MUg/mL for 10 minutes. In addition, the combination of nisin with low doses
      of NaOCl enhanced the antibiofilm properties of both antimicrobial agents.
      CONCLUSIONS: Nisin alone or in combination with low concentrations of NaOCl
      reduces the planktonic growth of E. faecalis and disrupts E. faecalis biofilm
      structure. Our results suggest that nisin has potential as an adjunctive
      endodontic therapeutic agent and as an alternative to conventional NaOCl
      irrigation.

PMID- 28457636
TI  - Transcriptomics Analysis Reveals Putative Genes Involved in Biofilm Formation and
      Biofilm-associated Drug Resistance of Enterococcus faecalis.
AB  - INTRODUCTION: Enterococcus faecalis is a gram-positive bacterium associated with
      endodontic infections and is capable of forming biofilms that can confer drug
      resistance to the bacterium, resulting in treatment failure. Current knowledge on
      E. faecalis drug resistance is of a limited and conflicting nature. The present
      study examined the genetic basis of E. faecalis biofilm formation and drug
      resistance using a RNA sequencing (RNA-Seq)-based transcriptome approach.
      METHODS: Eighteen clinical isolates of E. faecalis were screened for their
      biofilm formation abilities using the crystal violet assay, colony counting, and
      confocal imaging. Selected isolates were then evaluated for antibiotic
      susceptibility in planktonic and biofilm growth modes followed by RNA-Seq
      analysis of E. faecalis planktonic, biofilm, and vancomycin-treated biofilm
      samples and Kyoto Encyclopedia of Genes and Genomes mapping in order to identify
      genes associated with biofilm formation and drug resistance of E. faecalis.
      RESULTS: All 18 clinical isolates retained biofilm formation ability and were
      classified as strong, weak, or laboratory American Type Culture Collection
      strainlike biofilm formers. Interestingly, both the strong and weak biofilm
      forming isolates were uniformly resistant to ampicillin and vancomycin at the
      treated concentrations (256-4096 MUg/mL). RNA-Seq analysis of these isolates
      identified a total of 163 and 101 differentially regulated genes in planktonic
      versus biofilm and vancomycin-treated biofilm versus biofilm comparisons,
      respectively, with significant differences in arsenic resistance operon genes
      arsR and arsD, sporulation regulatory gene paiA, ABC drug transporter classes,
      and penicillin-binding proteins. CONCLUSIONS: The present transcriptomic study
      revealed putative genes associated with E. faecalis biofilm formation and drug
      resistance, which will provide a foundation for improved therapeutic strategies
      against E. faecalis infections in the future.

PMID- 28457637
TI  - Preexisting Dentinal Microcracks in Nonendodontically Treated Teeth: An Ex Vivo
      Micro-computed Tomographic Analysis.
AB  - INTRODUCTION: This study evaluated the prevalence, location, and pattern of
      preexisting dentinal microcracks in roots of extracted teeth without endodontic
      treatment in patients from 2 age groups using micro-computed tomographic imaging.
      METHODS: Six hundred thirty-three nonendodontically treated teeth extracted using
      an atraumatic procedure because of reasons unrelated to this study were collected
      and divided based on the patient age. Teeth were scanned with micro-computed
      tomographic imaging (resolution of 26.7 MUm) to examine the presence of
      preexisting dentinal microcracks in roots. The characteristic features of
      preexisting dentinal microcracks determined were location, extent, length, and
      coronoapical distribution. Chi-square bivariate analysis was performed to assess
      the association between various parameters. RESULTS: Forty-five of 633
      nonendodontically treated teeth exhibited preexisting microcracks in roots with a
      prevalence of 7.1%. The prevalence of preexisting microcracks was found to be
      8.3% in older patients (40-70 years) compared with 3.7% in younger patients (20
      39 years) (P < .050). A significant association was found between the preexisting
      microcracks in mandibular teeth (10.3%) when compared with maxillary teeth (2.9%)
      (P < .001). All preexisting microcracks were located mesiodistally; 66% occurred
      in the cervical and middle thirds of root. Only 33% of the preexisting
      microcracks were complete in nature, showing canal involvement. Complete dentinal
      microcracks exhibited a mean length of 6.9 mm, whereas incomplete cracks had a
      mean length of 3.75 mm (P < .001). CONCLUSIONS: Preexisting dentinal microcracks
      in roots of nonendodontically treated teeth occurred more often in older patients
      (40-70 years) in the mesiodistal direction. They were predominantly found in the
      cervical and middle thirds of root and were more likely to be incomplete in
      nature.

PMID- 28457638
TI  - Provider Perceptions of Treatment Options for Immature Permanent Teeth.
AB  - INTRODUCTION: Current treatment options for immature permanent teeth with pulpal
      necrosis include both apexification and regenerative endodontics. The purpose of
      this study was to survey endodontists on the use of these 2 treatment options.
      METHODS: Surveys were created by using Qualtrics and Teleform software and
      distributed by using the Salant and Dillman method. Endodontists (n = 1615) in 4
      geographically and demographically diverse states, North Carolina, New York,
      Texas, and California, were surveyed. Data were analyzed by using descriptive
      statistics and chi2 analysis. Level of significance was set at 0.05. RESULTS: A
      32.9% response rate was obtained. The majority of responders reported that
      apexification was the treatment of choice when considering the evidence base
      supporting the treatment (60%) and the predictability of treatment outcome
      (77.8%). Apexification was also the preferred treatment by 57.3% of respondents
      when asked to consider patient compliance, by 51.2% when considering the number
      of required patient appointments, and by 53.3% when considering the likelihood of
      tooth discoloration. Regenerative endodontics was reported as the preferred
      treatment by 89% of respondents when considering continued root development and
      by 66.7% when considering apical closure. The respondents' age and continuing
      education courses taken were significantly associated with their preferred
      treatment option. CONCLUSIONS: The results of our study indicate that
      endodontists consider both clinical and patient factors when treating immature
      teeth with pulpal necrosis. Increase in continuing education options may increase
      adoption of regenerative endodontic therapy.

PMID- 28457639
TI  - Endodontic Treatment in Single and Multiple Visits: An Overview of Systematic
      Reviews.
AB  - INTRODUCTION: The effectiveness of endodontic treatment regarding the number of
      sessions to complete the therapy is still controversial. The aim of this study
      was to conduct an overview of published systematic reviews (SRs) comparing
      endodontic treatment in single and multiple visits. METHODS: A systematic search
      was performed in the electronic databases MEDLINE/PubMed and Cochrane Central
      Register of Controlled Trials until August 18, 2016, without language
      restriction. The eligibility criteria were as follows: (1) SRs and (2) a focus on
      endodontic techniques in single or multiple visits. The phases of eligibility and
      analysis of risk of bias were conducted by 2 or 3 independent and calibrated
      examiners, and a fourth examiner was consulted to resolve inconsistencies.
      Assessment of Multiple Systematic Reviews was used to evaluate the risk of bias
      of the included SRs, which were assessed according to the risk to develop
      knowledge and the existing knowledge gap. RESULTS: The main characteristics
      including healing rates, success, and clinical complications during and after
      endodontic treatment were extracted from the SRs. From the 20 SRs initially
      identified, 8 were included in the analysis. Of these, 6 SRs showed low to
      moderate risk of bias and were suitable as strong clinical evidence on the topic.
      CONCLUSIONS: Overall analysis indicated that single and multiple visits showed
      similar repair or success rates regardless of the precondition of the pulp and
      periapex. The apical periodontitis subgroup showed a slight positive trend toward
      a decreased incidence of postoperative complications and a higher effectiveness
      and efficiency for a single session. Based on the risk of bias, the current level
      of evidence for this clinical approach is high.

PMID- 28457640
TI  - Whole-organism concentration ratios in wildlife inhabiting Australian uranium
      mining environments.
AB  - Wildlife concentration ratios for 226Ra, 210Pb, 210Po and isotopes of Th and U
      from soil, water, and sediments were evaluated for a range of Australian uranium
      mining environments. Whole-organism concentration ratios (CRwo-media) were
      developed for 271 radionuclide-organism pairs within the terrestrial and
      freshwater wildlife groups. Australian wildlife often has distinct physiological
      attributes, such as the lower metabolic rates of macropod marsupials as compared
      with placental mammals. In addition, the Australian CRswo-media originate from
      tropical and semi-arid climates, rather than from the temperate-dominated
      climates of Europe and North America from which most (>90%) of internationally
      available CRwo-media values originate. When compared, the Australian and non
      Australian CRs are significantly different for some wildlife categories (e.g.
      grasses, mammals) but not others (e.g. shrubs). Where differences exist, the
      Australian values were higher, suggesting that site-, or region-specific CRswo
      media should be used in detailed Australian assessments. However, in screening
      studies, use of the international mean values in the Wildlife Transfer Database
      (WTD) appears to be appropriate, as long as the values used encompass the
      Australian 95th percentile values. Gaps in the Australian datasets include a lack
      of marine parameters, and no CR data are available for freshwater phytoplankton,
      zooplankton, insects, insect larvae or amphibians; for terrestrial environments,
      there are no data for amphibians, annelids, ferns, fungi or lichens & bryophytes.
      The new Australian specific parameters will aide in evaluating remediation plans
      and ongoing operations at mining and waste sites within Australia. They have also
      substantially bolstered the body of U- and Th-series CRwo-media data for use
      internationally.

PMID- 28457641
TI  - Premature Infant Care in the Early 20th Century.
AB  - The complex early history of infant incubators provides insight into challenges
      faced by medical professionals as they promoted care for premature infants in the
      early 20th century. Despite their absence from the narrative to date, nurses
      played vital roles in the development of neonatal care. Working in many different
      settings, from incubator-baby shows to the first hospital unit designed
      specifically for premature infants, nurses administered quality care and promoted
      advanced treatment for these newborns.

PMID- 28457642
TI  - Systemic reaction to timothy grass pollen sublingual immunotherapy.

PMID- 28457644
TI  - Vaccine allergy: A decade of experience from 2 large UK allergy centers.

PMID- 28457643
TI  - Risk of obstructive sleep apnea in African American patients with chronic
      rhinosinusitis.
AB  - BACKGROUND: It is widely known that patients with chronic rhinosinusitis (CRS)
      commonly experience sleep disruption. Many of these patients have the associated
      diagnosis of obstructive sleep apnea (OSA). However, little is known about the
      risk factors for developing OSA in the CRS population. OBJECTIVE: To identify the
      risk factors for OSA in CRS to determine who should be screened for OSA among
      patients with CRS. METHODS: We evaluated a large cohort of patients with
      confirmed diagnostic criteria for CRS. Patient medical records were reviewed to
      identify those with OSA confirmed by overnight polysomnography. Records were
      further reviewed for demographic information (age, sex, race, and ethnicity),
      body mass index, and medical history, including the presence of nasal polyps,
      asthma, aspirin-exacerbated respiratory disease, allergic rhinitis, and eczema.
      The number of endoscopic sinus operations, duration of CRS, presence of
      subjective smell loss, and computed tomography Lund-Mackay score were also
      ascertained. RESULTS: A total of 916 patients with CRS were included in the
      study. Implementation of a multivariable regression model for identifying
      adjusted risk factors revealed that African American patients had a significantly
      higher risk for OSA than white patients, with an adjusted odds ratio of 1.98 (95%
      confidence interval, 1.19-3.29). Furthermore, patients with CRS without nasal
      polyps were at higher risk for OSA, with an odds ratio of 1.63 (95% confidence
      interval, 1.02-2.61) compared with patients with CRS with nasal polyps.
      CONCLUSION: African American patients with CRS were at higher risk for OSA
      compared with white patients, and this patient group needs to be screened for
      OSA.

PMID- 28457645
TI  - Toxicological and thermoregulatory effects of feather contamination with
      artificially weathered MC 252 oil in western sandpipers (Calidris mauri).
AB  - The external contamination of bird feathers with crude oil might have effects on
      feather structure and thus on thermoregulation. We tested the thermoregulatory
      ability of western sandpipers (Calidris mauri) in a respirometry chamber with oil
      applied either immediately prior, or three days before the experiment. The birds
      were then exposed to a sliding cold temperature challenge between 27 degrees C
      and -3 degrees C to calculate thermal conductance. After the experiment, a large
      blood sample was taken and the liver extracted to measure a range of parameters
      linked to toxicology and oxidative stress. No differences in thermal conductance
      were observed among groups, but birds exposed to oil for three days had reduced
      body temperatures and lost more body mass during that period. At necropsy, oiled
      birds showed a decrease in plasma albumin and sodium, and an increase in urea.
      This is reflective of dysfunction in the kidney at the loop of Henle. Birds,
      especially when exposed to the oil for three days, showed signs of oxidative
      stress and oxidative damage. These results show that the ingestion of externally
      applied oil through preening or drinking can cause toxic effects even in low
      doses, while we did not detect a direct effect of the external oil on
      thermoregulation over the temperature range tested.

PMID- 28457646
TI  - [Molecular identification and in vitro antifungal susceptibility of blood
      isolates of the Candida parapsilosis species complex in Venezuela].
AB  - BACKGROUND: Candida parapsilosis is a species complex consisting of Candida
      parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis.
      Studies worldwide have described its epidemiology and susceptibility to
      antifungal agents. AIMS: The aims of this study were to carry out the molecular
      identification of blood isolates belonging to the Candida parapsilosis species
      complex, and to determine their in vitro susceptibility to antifungals of
      systemic use. METHODS: A study of 86 strains of C. parapsilosis species complex
      collected in 2008-2011 and obtained from the Candidaemia Surveillance Network of
      Mycology Department of the Rafael Rangel National Institute of Hygiene, was made.
      Secondary alcohol-dehydrogenase gene amplification was performed using polymerase
      chain reaction, and the products were analysed by restriction fragments length
      polymorphisms using the enzyme BanI. Susceptibility tests were performed using
      Etest(r), following the manufacturer's instructions with modifications. RESULTS:
      Of the 86 isolates studied, 81 (94.2%) were C. parapsilosis sensu stricto, 4
      (4.6%) C. orthopsilosis, and one (1.2%) C. metapsilosis. C. parapsilosis isolates
      were susceptible to amphotericin B and caspofungin, showing low rates of
      resistance to fluconazole and voriconazole. C. orthopsilosis and C. metapsilosis
      were susceptible to all the antifungals tested. CONCLUSIONS: The results obtained
      in Venezuela provide for the first time important information about the
      distribution of C. parapsilosis species complex in cases of candidaemia, and
      support the need for continuing surveillance programs, including molecular
      discrimination of species and antifungal susceptibility tests, which may guide
      specific therapy.

PMID- 28457647
TI  - British Gynaecological Cancer Society (BGCS) epithelial ovarian/fallopian
      tube/primary peritoneal cancer guidelines: recommendations for practice.

PMID- 28457648
TI  - Circulating testosterone and feather-gene expression of receptors and metabolic
      enzymes in relation to melanin-based colouration in the barn owl.
AB  - Knowledge of how and why secondary sexual characters are associated with sex
      hormones is important to understand their signalling function. Such a link can
      occur if i) testosterone participates in the elaboration of sex-traits, ii) the
      display of an ornament triggers behavioural response in conspecifics that induce
      a rise in testosterone, or iii) genes implicated in the elaboration of a sex
      trait pleiotropically regulate testosterone physiology. To evaluate the origin of
      the co-variation between melanism and testosterone, we measured this hormone and
      the expression of enzymes involved in its metabolism in feathers of barn owl
      (Tyto alba) nestlings at the time of melanogenesis and in adults outside the
      period of melanogenesis. Male nestlings displaying smaller black feather spots
      had higher levels of circulating testosterone, potentially suggesting that
      testosterone could block the production of eumelanin pigments, or that genes
      involved in the production of small spots pleiotropically regulate testosterone
      production. In contrast, the enzyme 5alpha-reductase, that metabolizes
      testosterone to DHT, was more expressed in feathers of reddish-brown than light
      reddish nestlings. This is consistent with the hypothesis that testosterone might
      be involved in the expression of reddish-brown pheomelanic pigments. In breeding
      adults, male barn owls displaying smaller black spots had higher levels of
      circulating testosterone, whereas in females the opposite result was detected
      during the rearing period, but not during incubation. The observed sex- and age
      specific co-variations between black spottiness and testosterone in nestling and
      adult barn owls may not result from testosterone-dependent melanogenesis, but
      from melanogenic genes pleiotropically regulating testosterone, or from colour
      specific life history strategies that influence testosterone levels.

PMID- 28457650
TI  - Orthostatic myoclonus after brain tumor radiation: Insights from two lesional
      cases.
AB  - INTRODUCTION: Orthostatic myoclonus (OM) is a recognized syndrome of gait
      unsteadiness accompanied by lower limb myoclonus provoked by the assumption of an
      upright posture. OM typically affects the elderly and is often associated with
      neurodegenerative disease. We sought to review the clinical and
      electrophysiologic characteristics of OM due to brain tumor treatment, the first
      reported lesional cases of this rare disorder. METHODS: The database of the Mayo
      Clinic Rochester Movement Disorders Laboratory was searched for all patients
      diagnosed with OM from January 2007 to December 2016. All available clinical,
      radiographic, and surface electromyographic data were reviewed, and patients with
      a history of primary or metastatic brain tumor were analyzed. RESULTS: Two
      patients with OM and brain tumor were identified; both had undergone tumor
      resection and targeted brain radiation. Both patients complained of unsteadiness
      while walking and recurrent falls. Tumor pathology (atypical meningioma,
      gliosarcoma) was centered in the frontal lobe and extended to the supplementary
      motor area (SMA), pre-SMA, or prefrontal cortex. Medications did not improve
      gait. CONCLUSION: Two cases of brain tumor-related OM suggest that degeneration
      of frontal motor programming circuits underlies the pathophysiology of OM.

PMID- 28457649
TI  - Diabetes after Bariatric Surgery.
AB  - Bariatric surgery has now emerged as an effective means of glycemic control in
      individuals with diabetes and obesity. However, long-term data show recurrence of
      hyperglycemia years after the procedure. Although the exact prevalence of
      diabetes relapse is unknown because of attrition and limited data on long-term
      follow up after the surgery, a significant percentage of patients experience
      relapse of diabetes. The mechanism of diabetes relapse is not completely
      understood and is not always linked to weight regain. The clinical implications
      of hyperglycemia after bariatric surgery for patients and healthcare providers is
      reviewed.

PMID- 28457651
TI  - Prevalence and correlates of mental health problems in prostate cancer survivors:
      A case-control study comparing survivors with general population peers.
AB  - OBJECTIVE: The purpose of this study was to identify factors associated with
      mental health (MH) problems in prostate cancer (PC) survivors. Toward this end,
      we evaluated (1) differences in the prevalence of MH problems between PC
      survivors and age-matched men from the general population (GenPop) and (2)
      correlates of MH in PC survivors and the GenPop. METHODS AND MATERIALS: In this
      observational case-control study, we age-matched PC survivors (n = 644, alive>=5y
      after diagnosis of a stage I-IV carcinoma) recruited from Dutch community
      hospitals (Patient Reported Outcomes Following Initial treatment and Long-term
      Evaluation of Survivorship registry) with GenPop peers (n = 644) selected from a
      population-based sample recruited in general practices (NIVEL). MH was
      operationalized using the 5-item Mental Health Inventory of the Short Form Health
      Survey (SF-36). Potential correlates of MH included sociodemographic
      characteristics, health-related quality of life scores, and clinical
      characteristics (PC survivors only). We used analysis of (co)variance and chi
      square tests to address the 2 research questions. RESULTS: We observed clinically
      relevant MH symptoms in 14% of the PC survivors and 6% of the GenPop controls
      (P<0.01, odds ratio = 2.45 [1.66-3.62]). The most important correlates of lower
      MH scores in the PC survivors were being widowed, a lower educational level,
      lower general health perceptions, more bodily pain and urinary bother, and less
      sexual satisfaction. The most important correlates of lower MH scores in the
      GenPop were as follows: lower general health perceptions, more role limitations
      because of physical problems, and more bodily pain. CONCLUSIONS: Our results
      indicate that long-term PC survivors have poorer MH, as assessed by the 5-item
      Mental Health Inventory questionnaire, than men of a comparable age from the
      GenPop without a history of PC. Attention to potentially modifiable factors
      associated with MH problems in PC survivors, such as urinary function and its
      related bother, bodily pain, and sexual satisfaction, may help to prevent or
      limit MH problems in this survivor population.

PMID- 28457652
TI  - Plasmid-mediated colistin resistance in Escherichia coli recovered from healthy
      poultry.

PMID- 28457653
TI  - Study of the relationship between APOA-II -265T>C polymorphism and HDL function
      in response to weight loss in overweight and obese type 2 diabetic patients.
AB  - BACKGROUND: It has been reported that people may respond differently to the same
      environmental changes because of genome variations. OBJECTIVE: The main purpose
      of the present study is to determine gene-diet interactions between -265T>C
      apolipoprotein A-II polymorphisms and evaluate the effect of weight loss on
      parameters related to HDL function. METHODS: In the present study, 56 overweight
      and obese type 2 diabetic patients were chosen from 697 genotype-specified
      subjects. After matching for gender, age and BMI, an equal number of patients
      were chosen for each genotype of APOA-II (TT/TC and CC group). After six-week
      calorie restriction programme, 44 patients completed the study. Serum paraoxonase
      1 (PON1), paraoxonase-3 (PON3), pentraxin-3 (PTX3), and PTX3 gene expression in
      peripheral blood mononuclear cells were compared between two genotypes and also
      before and after the intervention separated in each genotype. RESULTS: The mean
      differences of PON enzymes and PTX3 between groups were not significant at the
      baseline. After weight loss, the mean weight, BMI and serum concentration of PON1
      and PON3 decreased significantly and PTX3 increased in total population.
      Although, the mean differences of PON enzymes and PTX3 between two groups were
      not significant. However, in comparison of mean differences within the groups,
      decreased PON3 and increased PTX3 have been observed only in TT group.
      CONCLUSION: A comparison of the mean differences in PON3 and PTX3 within two
      genotype groups showed that T allele carriers are more sensitive to lifestyle
      modification, and serum PON3 and PTX3 levels significantly changed only in the
      TT/TC group.

PMID- 28457654
TI  - Effect of nut consumption on vascular endothelial function: A systematic review
      and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: nut consumption has consistently been found to be associated with a
      reduced risk of cardiovascular diseases (CVD) and mortality in prospective
      studies. However, its effect on endothelial function, a prognostic marker of CVD,
      is still controversial in clinical trials. This meta-analysis of randomized
      controlled trials (RCTs) aimed to quantitatively assess the effect of nuts on
      vascular endothelial function. METHODS: Major electronic databases were searched
      for published RCTs that reported the effect of nuts on flow mediated dilation
      (FMD) as a measurement of endothelial function in the adult population (age
      eighteen years or over). We calculated the pooled estimates of weighted mean
      differences (WMDs) and their 95% confidence intervals (CIs) by using random
      effects models. RESULTS: A total of nine papers (10 trials) involving 374
      participants were included. The pooled estimates found that nut consumption
      significantly improved FMD (WMD: 0.41%; 95% CI: 0.18%, 0.63%; P = 0.001).
      Moderate and marginally significant heterogeneity was observed among the studies
      (I2 = 39.5%, P = 0.094). Subgroup analyses indicated that walnuts significantly
      improved FMD (WMD: 0.39%; 95% CI: 0.16%, 0.63%; P = 0.001). In addition, nut
      consumption had a significant effect on FMD in the trials with study duration <18
      weeks, nut dose <67 g/d, or subjects with baseline FMD >=8.6%. CONCLUSIONS: Nut
      consumption significantly improved endothelial function. However, the beneficial
      effect was limited to walnuts. More studies examining the effect of other nuts on
      endothelial function are needed in the future.

PMID- 28457655
TI  - Mazinger, a gamma-ray spectrometry system of high efficiency and very low
      background for paloeoclimate applications.
AB  - The study of changes in climate on the scale of the entire history of Earth
      requires absolute dating methods that cover the total time period. 230Th and 234U
      disequilibria, as well as 231Pa and 235U, have shown as good candidates to
      provide ages older than 50ky. Therefore, they are the basis for a method that
      allows extending the 14C dating up to 500ky or even further. The wide variety of
      samples, their high number and the fact that several radionuclides are needed to
      obtain samples' chronology make gamma spectrometry to be a suitable technique in
      this task. However, its low efficiency and high background, therefore, high
      detection limits in comparison with alpha spectrometry, need to be improved to
      become a real alternative in samples with very low activity levels. With this
      purpose, Mazinger, a new gamma spectrometry system based on two HPGe detectors,
      which are surrounded by active and passive shieldings and placed 12m underground,
      has been set up in the Ionizing Radiation Laboratory of the University of
      Salamanca. In this work, the Mazinger's performance is studied at the full energy
      range useful for natural radionuclides. In composite detectors, energy resolution
      is a consequence of the electronics adjustments, which have to enable the raw
      spectra to be summed without resolution worsening. Therefore, the method used to
      set up electronics and add spectra is described. Detector background is also
      analysed and compared with the one of a single low-background HPGe detector as a
      function of the different shielding elements, obtaining gross values of order 10
      4cps. Efficiency and figure of merit are obtained for the main natural
      radionuclides in marine sediments belonging to the Mediterranean MD99-2348 core.
      Special focus is made on the 230Th determination whose results are compared with
      the ones provided by alpha spectrometry. Results show that Mazinger's
      performance, in terms of figure of merit, is four times better than the one of a
      low-level background HPGe detector, specially suited to detect natural
      radionuclides, being comparable to the performance of alpha spectrometry in the
      230Th determination, which is the radionuclide of lower gamma intensity, and
      doing Mazinger a first class in radiometry of natural radionuclides.

PMID- 28457656
TI  - Stimulating Patient Engagement in Medical Device Development in Kidney Disease: A
      Report of a Kidney Health Initiative Workshop.
AB  - New technologies challenge current dialysis treatment paradigms as devices become
      smaller, more portable, and increasingly used outside the dialysis clinic. It is
      unclear how patients will view this care transition, and it will be important to
      consider patient and care partner perspectives during all aspects of development
      for novel dialysis therapies, from design and clinical trials to regulatory
      approval. To gain insight into this area, the Kidney Health Initiative, a public
      private partnership between the American Society of Nephrology, the US Food and
      Drug Administration, and nearly 80 member organizations and companies dedicated
      to enhancing patient safety and fostering innovation in kidney disease, convened
      a workshop of patients, care partners, and other kidney community stakeholders.
      The workshop included background presentations followed by focused small group
      discussions in 3 areas (device design, clinical trials, and regulatory approval).
      Participants explored how to involve patients throughout the life cycle of a
      medical device, including discussions of how patients can influence device
      design, assist in the planning and implementation of clinical trials, and provide
      input to affect regulatory decisions. Patients were engaged in the workshop
      discussion and interested in sharing their perspectives, but they recommended
      additional efforts around education, communication, and outreach in these areas.

PMID- 28457657
TI  - Stem cell transplantation for immunoglobulin light chain amyloidosis.
AB  - Systemic chemotherapy aimed at eradicating transformed plasma cells is the
      mainstay of treatment for immunoglobulin light chain amyloidosis (AL). Autologous
      stem cell transplantation (SCT) is a highly effective treatment for AL and can
      lead to long term survival in excess of 10 years in patients who achieve complete
      remission. Since AL is a unique disease characterized by multiple organ
      dysfunction, SCT poses unique challenges in this disease. Morbidity and mortality
      of SCT has remarkably improved over time primarily due to careful selection of
      patients and evolution of predictive and prognostic models based on serum
      immunoglobulin light chains and cardiac biomarkers. In this review we focus on
      the historical evolution of SCT as a treatment for AL and unique challenges it
      poses in the management of this rare disease and provide guidelines for managing
      these challenges.

PMID- 28457658
TI  - Pilot scale production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate)
      biopolymers with high molecular weight and elastomeric properties.
AB  - Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [(P(3HB-co-4HB)] copolymer receives
      attention as next generation biomaterial in medical application. However, the
      exploitation of the copolymer is still constrained since such copolymer has not
      yet successfully been performed in industrial scale production. In this work, we
      intended to establish pilot production system of the copolymer retaining the
      copolymer quality which has recently discovered to have novel characteristic from
      lab scale fermentation. An increase of agitation speed has significantly improved
      the copolymer accumulation efficiency by minimizing the utilization of substrates
      towards cell growth components. This is evidenced by a drastic increase of PHA
      content from 28 wt% to 63 wt% and PHA concentration from 3.1 g/L to 6.5 g/L but
      accompanied by the reduction of residual biomass from 8.0 g/L to 3.8 g/L.
      Besides, fermentations at lower agitation and aeration have resulted in reduced
      molecular weight and mechanical strength of the copolymer, suggesting the role of
      sufficient oxygen supply efficiency in improving the properties of the resulting
      copolymers. The KLa-based scale-up fermentation was performed successfully in
      maintaining the yield and the quality of the copolymers produced without a
      drastic fluctuation. This suggests that the scale-up based on the KLa values
      supported the fermentation system of P(3HB-co-4HB) copolymer production in single
      stage using mixed-substrate cultivation strategy.

PMID- 28457659
TI  - Estimation of the influence of sequencing errors and distribution of random
      sequence tags on quantitative sequencing.
AB  - To simultaneously sequence and quantify target DNA, quantitative sequencing
      (qSeq) employs stochastic labeling of target DNA molecules with random-sequence
      tags (RSTs). This recently developed approach allows parallel quantification of
      hundreds of microorganisms in natural habitats in a single sequencing run. Yet,
      no study has addressed to what extent sequencing errors affect quantification and
      how many sequence reads are needed for quantification. Here, we addressed those
      issues by using numerical simulations and experimental data from second
      generation sequencing of various RSTs. We found that heterogeneous distribution
      of observed RSTs affected the number of sequence reads required to quantitate
      target genes, whereas the effect of sequencing errors is smaller than of the RSTs
      distribution. Because of the heterogeneous RSTs distribution, 15-fold more
      sequence reads than the number of observed RSTs should be obtained to retrieve
      almost all RSTs needed for quantification; in that case, quantification error is
      estimated to be within 5%.

PMID- 28457660
TI  - ILK regulates MSCs survival and angiogenesis partially through AKT and mTOR
      signaling pathways.
AB  - Mesenchymal stem cells (MSCs) exert therapeutic effects on treating acute
      myocardial infarction (AMI). Angiogenesis in ischemic heart can promote the
      supply of oxygen and nutrients to both ischemic myocardium and transplanted stem
      cells. Focus is then given to the evolving strategies amied at angiogenesis. ILK
      has been reported to be an important factor regulating apoptosis and
      angiogenesis. This study examined the role and mechanism of ILK in MSCs survival
      and angiogenesis. In hypoxic condition, upregulation of ILK expression increased
      the phosphorylation of Akt and mTOR, resulting in markedly enchanced MSCs
      survival and VEGF expression; while significantly inhibited MSCs survival and
      VEGF expression was detected in MSCs with ILK kinase inactivation, which was
      associated with a reduction of phosphorylation of Akt and mTOR. In addition, it
      also caused an inhibitory effects of ILK on MSCs survival and VEGF expression,
      which was abolished by Akt or mTOR inhibitor. Furthermore, it was observed that
      ILK-overexpressed MSCs increased MSCs survival at 4days and angiogenesis at 3
      weeks after transplantation into infracted myocardium as compared with GFP-MSCs
      group and ILK-SiRNA-MSCs group. This enhanced response was associated with
      attenuated left ventricular (LV) chamber dilation, reduced LV fibrosis, decreased
      infarct size and improved LV function. These findings reveal ILK play a pivotal
      role in regulating MSCs survival and VEGF expression partially through Akt and
      mTOR signaling pathway. In addition, transplantation of ILK-overexpressed MSCs
      into infracted myocardium resulted in reduced fibrosis, improved cardiac function
      and remodeling, which mainly medicated through increased MSCs survival and
      angiogenesis.

PMID- 28457661
TI  - Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health
      Organization Grading Classification Systems in Non-muscle-invasive Bladder
      Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer
      Guidelines Panel Systematic Review.
AB  - CONTEXT: Tumour grade is an important prognostic indicator in non-muscle-invasive
      bladder cancer (NMIBC). Histopathological classifications are limited by
      interobserver variability (reproducibility), which may have prognostic
      implications. European Association of Urology NMIBC guidelines suggest concurrent
      use of both 1973 and 2004/2016 World Health Organization (WHO) classifications.
      OBJECTIVE: To compare the prognostic performance and reproducibility of the 1973
      and 2004/2016 WHO grading systems for NMIBC. EVIDENCE ACQUISITION: A systematic
      literature search was undertaken incorporating Medline, Embase, and the Cochrane
      Library. Studies were critically appraised for risk of bias (QUIPS). For
      prognosis, the primary outcome was progression to muscle-invasive or metastatic
      disease. Secondary outcomes were disease recurrence, and overall and cancer
      specific survival. For reproducibility, the primary outcome was interobserver
      variability between pathologists. Secondary outcome was intraobserver variability
      (repeatability) by the same pathologist. EVIDENCE SYNTHESIS: Of 3593 articles
      identified, 20 were included in the prognostic review; three were eligible for
      the reproducibility review. Increasing tumour grade in both classifications was
      associated with higher disease progression and recurrence rates. Progression
      rates in grade 1 patients were similar to those in low-grade patients;
      progression rates in grade 3 patients were higher than those in high-grade
      patients. Survival data were limited. Reproducibility of the 2004/2016 system was
      marginally better than that of the 1973 system. Two studies on repeatability
      showed conflicting results. Most studies had a moderate to high risk of bias.
      CONCLUSIONS: Current grading classifications in NMIBC are suboptimal. The 1973
      system identifies more aggressive tumours. Intra- and interobserver variability
      was slightly less in the 2004/2016 classification. We could not confirm that the
      2004/2016 classification outperforms the 1973 classification in prediction of
      recurrence and progression. PATIENT SUMMARY: This article summarises the utility
      of two different grading systems for non-muscle-invasive bladder cancer. Both
      systems predict progression and recurrence, although pathologists vary in their
      reporting; suggestions for further improvements are made.

PMID- 28457662
TI  - Corrigendum re: "Early Recurrence Patterns Following Totally Intracorporeal Robot
      assisted Radical Cystectomy: Results from the EAU Robotic Urology Section (ERUS)
      Scientific Working Group" [Eur Urol 2017;71:723-6].

PMID- 28457663
TI  - Meat flavour in pork and beef - From animal to meal.
AB  - An intense meat flavour is greatly appreciated by consumers. Meat flavour is
      generated during the cooking process through a complex series of chemical
      reactions between precursors, intermediate reaction products and degradation
      products. The content and nature of the precursors present in the meat are
      affected by several factors including genetics, feed, handling of the live
      animals and subsequent handling of the meat. The fatty acid composition can
      easily be altered though feeding, especially in monogastric animals, while the
      carbohydrate content is more closely related to genetics (pigs), feeding in the
      last days before slaughter and handling at slaughter (both ante and post mortem).
      Ageing of the meat is not particularly important for the flavour, unless the meat
      is dry-aged. In comparison, cooking is crucial for the development of flavour.

PMID- 28457664
TI  - In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver
      Metastases.
AB  - Multiple therapeutic agents are typically used in concert to effectively control
      metastatic tumors. Recently, we described microRNAs that are associated with the
      oligometastatic state, in which a limited number of metastatic tumors progress to
      more favorable outcomes. Here, we report the effective delivery of an
      oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using
      nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and
      prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted
      microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin,
      suggesting additive or synergistic interactions between microRNAs and platinum
      drugs. This is the first known example of systemically administered nanoparticles
      delivering an oligometastatic microRNA to advanced metastatic liver tumors and
      demonstrating tumor-suppressive effects. Our results suggest a potential
      therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs
      and conventional cytotoxic agents using tumor-specific NCPs.

PMID- 28457666
TI  - Comments on the "Glyphosate herbicide residue determination in samples of
      environmental importance using spectrophotometric method".

PMID- 28457665
TI  - Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against
      H10N8 and H7N9 Influenza Viruses.
AB  - Recently, the World Health Organization confirmed 120 new human cases of avian
      H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a
      potential pandemic and the need for an effective, safe, and high-speed vaccine
      production platform. Production speed and scale of mRNA-based vaccines make them
      ideally suited to impede potential pandemic threats. Here we show that lipid
      nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin
      (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013),
      generated rapid and robust immune responses in mice, ferrets, and nonhuman
      primates, as measured by hemagglutination inhibition (HAI) and
      microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a
      lethal challenge and reduced lung viral titers in ferrets. Interim results from a
      first-in-human, escalating-dose, phase 1 H10N8 study show very high
      seroconversion rates, demonstrating robust prophylactic immunity in humans.
      Adverse events (AEs) were mild or moderate with only a few severe and no serious
      events. These data show that LNP-formulated, modified mRNA vaccines can induce
      protective immunogenicity with acceptable tolerability profiles.

PMID- 28457667
TI  - Extracorporeal shock wave lithotripsy (ESWL) monotherapy in children: Predictors
      of successful outcome.
AB  - INTRODUCTION AND OBJECTIVES: Although extracorporeal shock wave lithotripsy
      (ESWL) is the first choice for pediatric renal calculi <2 cm, the success rate
      after the first session is low. This is in contrast to other minimally invasive
      procedures like percutanous nephrolithotomy (PCNL) and retrograde intrarenal
      surgery (RIRS), which have higher rates of success. Therefore, the present study
      sought to identify predictors of success after one session of ESWL. PATIENTS AND
      METHODS: A prospective study including 100 children with renal stone burden <2 cm
      who underwent ESWL at the present institution. The success rate after the first
      session was analyzed, and the predictors of success were investigated. The
      success of ESWL monotherapy was defined by absence of any residual fragments
      after 3 months, on non-contrast spiral computerized tomography (NCCT) scan,
      without need of any additional intervention. RESULTS: Between January 2013 and
      October 2015, 100 children were treated with a Dornier Gemini lithotripter at the
      present institution. The mean patients age and stone size were 6 years (range:
      1.8-14) and 13.1 mm (range: 6-20), respectively. After one session, 47% of
      patients showed complete clearance 3 months postoperative, those patients versus
      those who required an additional session or auxiliary procedures were younger in
      age, with smaller stone size and lower density. On multivariate analysis, only
      patient age was an independent predictor of success (odds ratio (OR) 0.9; P <
      0.001). CONCLUSION: Patient's age was an important predictor for response after
      ESWL monotherapy: not only did children respond better than adults, but age was
      also an independent predictor within the pediatric group.

PMID- 28457668
TI  - Re: "Stites J, Bernabe KJ, Galan D, Felsen D, Poppas DP. Urinary continence
      outcomes following vaginoplasty in patients with congenital adrenal hyperplasia."
      J Pediatr Urol 2017;13:38.e1-38.e7 and Diamond DA. 'Commentary to "Urinary
      continence outcome following vaginoplasty in patients with congenital adrenal
      hyperplasia."' J Pediatr Urol 2017;13:39.

PMID- 28457670
TI  - Implications of altered autonomic control on sports performance in athletes with
      spinal cord injury.
AB  - It is well known that athletes with spinal cord injury (SCI) may experience
      altered autonomic physiology that impacts their exercise capacity and sports
      performance. This is particularly relevant given the ever-increasing number of
      individuals with SCI who are actively engaged in sports at all levels, from
      community-based adaptive sports to elite Paralympic competitions. As such, the
      purpose of this article is to review the present literature regarding the
      implications of altered autonomic control on the safety and performance of
      athletes with SCI. A particular emphasis will be placed on the autonomic aspects
      of cardiovascular and thermoregulatory control in the athlete population, as well
      as the implications of autonomic dysreflexia in enhancing sports performance.
      Further research is needed to understand the autonomic factors that influence
      athletes with SCI in order to ensure optimal and safe sports competition.
      Additionally, this information is crucially relevant to the coaches, sports
      administrators, and team medical staff who work closely with athletes with SCI.

PMID- 28457669
TI  - alpha6beta2 nicotinic acetylcholine receptors influence locomotor activity and
      ethanol consumption.
AB  - Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system have
      been implicated in ethanol behaviors. In particular, work in genetically
      engineered mice has demonstrated that alpha6-containing nAChRs are involved in
      ethanol consumption and sedation. A limitation of these studies is that the
      alteration in the receptor was present throughout development. The recently
      described alpha6beta2 antagonist, N,N-decane-1,10-diyl-bis-3-picolinium diiodide
      (bPiDI), now makes it possible to test for the involvement of these receptors
      using a pharmacological approach. The aim of this study was to examine the role
      of alpha6beta2 nAChRs in ethanol behaviors using a pharmacological approach.
      Adolescent C57BL/6J mice were treated with bPiDI 30 min prior to testing the mice
      for binge-like ethanol consumption in the drinking-in-the-dark (DID) test,
      ethanol-induced motor incoordination using the balance beam, and ethanol-induced
      sedation using the Loss of Righting Reflex (LORR) paradigm. Adolescent animals
      were chosen because they express a high amount of alpha6 mRNA relative to adult
      animals. Control studies were also performed to determine the effect of bPiDI on
      locomotor activity and ethanol metabolism. Female mice treated with 20 mg/kg
      bPiDI had reduced locomotor activity compared to saline-treated animals during
      the first 30 min following an acute injection. Pretreatment with the alpha6beta2
      antagonist reduced adolescent ethanol consumption but also reduced saccharin
      consumption. No significant effects were observed on ethanol-induced ataxia,
      sedation, or metabolism. This study provides evidence that alpha6beta2 nAChRs are
      involved in locomotor activity as well as ethanol and saccharin consumption in
      adolescent animals.

PMID- 28457671
TI  - Old and new challenges in Parkinson's disease therapeutics.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by the
      degeneration of dopaminergic neurons and/or loss od neuronal projections, in
      several dopaminergic networks. Current treatments for idiopathic PD rely mainly
      on the use of pharmacologic agents to improve motor symptomatology of PD
      patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is
      of utmost importance to establish new therapeutic strategies for PD treatment.
      Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic
      approaches have been developed with the aim of counteracting or retarding PD
      progression. The scope of this review is to provide an overview of PD related
      therapies and major breakthroughs achieved within this field. In order to do so,
      this review will start by focusing on PD characterization and current treatment
      options covering thereafter molecular, gene and cell/stem cell-based therapies
      that are currently being studied in animal models of PD or have recently been
      tested in clinical trials. Among stem cell-based therapies, those using MSCs as
      possible disease modifying agents for PD therapy and, specifically, the MSCs
      secretome contribution to meet the clinical challenge of counteracting or
      retarding PD progression, will be more deeply explored.

PMID- 28457672
TI  - Antibody persistence in children aged 6-7years one year following booster
      immunization with two MMR vaccines applied by aerosol or by injection.
AB  - IMPORTANCE: In a previous study on booster vaccination, we reported that two
      aerosolized MMR vaccines were as safe and immunogenic as injectable vaccines
      containing the same antigens. We now present results of antibody persistence one
      year after immunization. OBJECTIVE: To assess the antibody persistence for
      measles, mumps, and rubella one year following booster immunization. METHODS: We
      performed clinical and serological follow-up of participants in a previous study
      of Mexican children aged 6-7years, in which participants were randomized to four
      groups receiving, by aerosolized or by injection, the MMR SII vaccine (Serum
      Institute of India), or the MMR II (Merck Sharp & Dhome). We evaluated the
      antibody persistence by PRN test for measles and by ELISA for rubella and mumps.
      The occurrence of clinical events was evaluated via periodic visits of a nurse
      team to children's schools and homes. RESULTS: Of the 260 initial participants,
      241 completed one-year follow-up. There were only statistically significant
      differences in baseline seropositivity for mumps. One year after immunization,
      seropositivity in all groups was 100% for measles and rubella. The seropositivity
      rank for mumps was from 90.3% for the injected vaccine MMR II to 96.6% for
      vaccine MMR SII applied by aerosol; these differences were not statistically
      significant. With exception of the aerosolized vaccine MMR SII for the geometric
      mean titer (GMT) for measles, all study groups presented declination of GMT for
      the three viruses. The difference between the aerosolized vaccines MMR SII and
      MMR RII was statistically significant for mumps antibodies. Only mild clinical
      events were identified. CONCLUSION: Under conditions of no endemic transmission
      for measles and rubella, and of low circulation of mumps virus, school-aged
      children remained seropositive to the three viruses one year following booster
      immunization. The study was registered under CMN 2010-005 number at COFEPRIS
      (National Regulatory Authority).

PMID- 28457673
TI  - Awareness among adults of vaccine-preventable diseases and recommended
      vaccinations, United States, 2015.
AB  - BACKGROUND: Adults are recommended to receive select vaccinations based on their
      age, underlying medical conditions, lifestyle, and other considerations. Factors
      associated with awareness of vaccine-preventable diseases and recommended
      vaccines among adults in the United States have not been explored. METHODS: Data
      from a 2015 internet panel survey of a nationally representative sample of U.S.
      adults aged >=19years were analyzed to assess awareness of selected vaccine
      preventable diseases and recommended vaccines for adults. A multivariable
      logistic regression model with a predictive marginal approach was used to
      identify factors independently associated with awareness of selected vaccine
      preventable infections/diseases and corresponding vaccines. RESULTS: Among the
      surveyed population, from 24.6 to 72.1% reported vaccination for recommended
      vaccines. Awareness of vaccine-preventable diseases among adults aged >=19years
      ranged from 63.4% to 94.0% (63.4% reported awareness of HPV, 71.5% reported
      awareness of tetanus, 72.0% reported awareness of pertussis, 75.4% reported
      awareness of HZ, 75.8% reported awareness of hepatitis B, 83.1% reported
      awareness of pneumonia, and 94.0% reported awareness of influenza). Awareness of
      the corresponding vaccines among adults aged >=19years ranged from 59.3% to 94.1%
      (59.3% HZ vaccine, 59.6% HPV vaccine, 64.3% hepatitis B vaccine, 66.2%
      pneumococcal vaccine, 86.3% tetanus vaccines, and 94.1% influenza vaccine). In
      multivariable analysis, being female and being a college graduate were
      significantly associated with a higher level of awareness for majority of vaccine
      preventable diseases, and being female, being a college graduate, and working as
      a health care provider were significantly associated with a higher level of
      awareness for majority of corresponding vaccines. CONCLUSIONS: Although adults in
      this survey reported high levels of awareness for most vaccines recommended for
      adults, self-reported vaccination coverage was not optimal. Combining
      interventions known to increase uptake of recommended vaccines, such as patient
      reminder/recall systems and other healthcare system-based interventions, and
      ensuring patients' vaccination needs are assessed, are needed to improve
      vaccination of adults.

PMID- 28457674
TI  - Corrigendum to "Safety of quadrivalent live attenuated influenza vaccine in
      subjects aged 2-49years" [Vaccine 35 (2017) 1254-1258].

PMID- 28457675
TI  - Four-segmented Rift Valley fever virus-based vaccines can be applied safely in
      ewes during pregnancy.
AB  - Rift Valley fever virus (RVFV) causes severe and recurrent outbreaks on the
      African continent and the Arabian Peninsula and continues to expand its habitat.
      This mosquito-borne virus, belonging to the genus Phlebovirus of the family
      Bunyaviridae contains a tri-segmented negative-strand RNA genome. Previously, we
      developed four-segmented RVFV (RVFV-4s) variants by splitting the M-genome
      segment into two M-type segments each encoding one of the structural
      glycoproteins; Gn or Gc. Vaccination/challenge experiments with mice and lambs
      subsequently showed that RVFV-4s induces protective immunity against wild-type
      virus infection after a single administration. To demonstrate the unprecedented
      safety of RVFV-4s, we here report that the virus does not cause encephalitis
      after intranasal inoculation of mice. A study with pregnant ewes subsequently
      revealed that RVFV-4s does not cause viremia and does not cross the ovine
      placental barrier, as evidenced by the absence of teratogenic effects and virus
      in the blood and organs of the fetuses. Altogether, these results show that the
      RVFV-4s vaccine virus can be applied safely in pregnant ewes.

PMID- 28457676
TI  - Higher order chromatin structures are taking shape.

PMID- 28457677
TI  - Research Pearls: The Significance of Statistics and Perils of Pooling. Part 3:
      Pearls and Pitfalls of Meta-analyses and Systematic Reviews.
AB  - Within the health care environment, there has been a recent and appropriate trend
      towards emphasizing the value of care provision. Reduced cost and higher quality
      improve the value of care. Quality is a challenging, heterogeneous, variably
      defined concept. At the core of quality is the patient's outcome, quantified by a
      vast assortment of subjective and objective outcome measures. There has been a
      recent evolution towards evidence-based medicine in health care, clearly
      elucidating the role of high-quality evidence across groups of patients and
      studies. Synthetic studies, such as systematic reviews and meta-analyses, are at
      the top of the evidence-based medicine hierarchy. Thus, these investigations may
      be the best potential source of guiding diagnostic, therapeutic, prognostic, and
      economic medical decision making. Systematic reviews critically appraise and
      synthesize the best available evidence to provide a conclusion statement (a "take
      home point") in response to a specific answerable clinical question. A meta
      analysis uses statistical methods to quantitatively combine data from single
      studies. Meta-analyses should be performed with high methodological quality
      homogenous studies (Level I or II) or evidence randomized studies, to minimize
      confounding variable bias. When it is known that the literature is inadequate or
      a recent systematic review has already been performed with a demonstration of
      insufficient data, then a new systematic review does not add anything meaningful
      to the literature. PROSPERO registration and PRISMA (Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses) guidelines assist authors in the design
      and conduct of systematic reviews and should always be used. Complete
      transparency of the conduct of the review permits reproducibility and improves
      fidelity of the conclusions. Pooling of data from overly dissimilar
      investigations should be avoided. This particularly applies to Level IV evidence,
      that is, noncomparative investigations. With proper technique, systematic reviews
      and meta-analyses have the potential to be powerful investigations that
      efficiently assist clinicians in decision making.

PMID- 28457678
TI  - Research Pearls: The Significance of Statistics and Perils of Pooling. Part 2:
      Predictive Modeling.
AB  - The focus of predictive modeling or predictive analytics is to use statistical
      techniques to predict outcomes and/or the results of an intervention or
      observation for patients that are conditional on a specific set of measurements
      taken on the patients prior to the outcomes occurring. Statistical methods to
      estimate these models include using such techniques as Bayesian methods; data
      mining methods, such as machine learning; and classical statistical models of
      regression such as logistic (for binary outcomes), linear (for continuous
      outcomes), and survival (Cox proportional hazards) for time-to-event outcomes. A
      Bayesian approach incorporates a prior estimate that the outcome of interest is
      true, which is made prior to data collection, and then this prior probability is
      updated to reflect the information provided by the data. In principle, data
      mining uses specific algorithms to identify patterns in data sets and allows a
      researcher to make predictions about outcomes. Regression models describe the
      relations between 2 or more variables where the primary difference among methods
      concerns the form of the outcome variable, whether it is measured as a binary
      variable (i.e., success/failure), continuous measure (i.e., pain score at 6
      months postop), or time to event (i.e., time to surgical revision). The outcome
      variable is the variable of interest, and the predictor variable(s) are used to
      predict outcomes. The predictor variable is also referred to as the independent
      variable and is assumed to be something the researcher can modify in order to see
      its impact on the outcome (i.e., using one of several possible surgical
      approaches). Survival analysis investigates the time until an event occurs. This
      can be an event such as failure of a medical device or death. It allows the
      inclusion of censored data, meaning that not all patients need to have the event
      (i.e., die) prior to the study's completion.

PMID- 28457679
TI  - High-risk cutaneous malignancies and immunosuppression: Challenges for the
      reconstructive surgeon in the renal transplant population.
AB  - Renal transplantation is the most frequently performed transplant procedure.
      Immunosuppressive therapies have dramatically increased survival rates in
      transplant recipients but are associated with an increased risk of skin cancers.
      Recent changes in immunosuppressive strategies have been adopted with the aim of
      reducing this challenging adverse effect. Despite these new strategies, cutaneous
      malignancies tend to be numerous, aggressive and associated with a higher risk of
      local and distant dissemination than in the non-transplant population. This
      represents a significant workload for transplant physicians, dermatologists, and
      head and neck and plastic surgeons. This review highlights key concepts in the
      pathogenesis of skin cancer in transplant patients, the impact current and
      evolving immunosuppressive strategies and regimens will have on the epidemiology,
      and the management of cutaneous malignancies in renal transplant patients, with
      particular focus on the implications for the plastic surgery community.

PMID- 28457680
TI  - [Hypocomplementemic urticarial vasculitis].
AB  - Hypocomplementemic urticarial vasculitis (HUV), called anti-C1q vasculitis in the
      2012 revised International Chapel Hill Consensus Conference Nomenclature of
      Vasculitides, is a rare systemic vasculitis of unknown etiology, affecting small
      vessels. HUV is characterized by urticarial lesions, hypocomplementemia and
      systemic manifestations, mostly musculoskeletal and ocular, but also
      gastrointestinal, pulmonary and kidney involvement. Anti-C1q antibodies are
      detected in only half of the patients, and low C1q seems to represent a more
      sensitive marker. Published data on the therapeutic management are scarce in the
      literature. Hydroxychloroquine and colchicine seem to represent effective first
      line therapies. In patient with relapsing or refractory disease, response rates
      appeared slightly higher for corticosteroids together with conventional
      immunosuppressive agents, in particular azathioprine, mycophenolate mofetil, or
      cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy.
      The best strategy for treating HUV has yet to be defined.

PMID- 28457681
TI  - [The plague: A disease that is still haunting our collective memory].
AB  - Although the plague has practically disappeared from Europe since the beginning
      of the 20th century, it is still present in everyone's memory. Owing to three
      pandemics, it has left an indelible mark on mankind and has given rise to many
      popular phrases, paintings, books or more recently movies and video games. After
      a brief description of the plague as a disease, we will try to trace the history
      of the plague through some of the works of art it inspired and then to show how
      the plague is still haunting our collective memory.

PMID- 28457682
TI  - [Quality of life measures in SLE: An update].
AB  - Systemic lupus erythematosus (SLE) is a chronic disease that considerably hampers
      patient's daily living. Qualitative studies with patients' interviews have been
      conducted to describe the experiences and perspectives of adults living with SLE.
      Among existing generic and disease-specific quality of life (QOL) questionnaires,
      none succeeded to exhaustively measure patient's preoccupations. However, these
      tools are useful to quantify the burden of the disease. Social precariousness,
      socioeconomic status and education level are intimately correlated to QOL
      measures, either generic or disease-specific. Musculoskeletal disease activity is
      also associated with a lower QOL. Using disease-specific tools may be useful
      because of a better aptitude to record an improvement in health status. Moreover,
      using generic and disease-specific questionnaires together may help to identify
      factors associated with a lower quality of life but not related to SLE from the
      patient's perspective (such as smoking or obesity). Developing new ways of
      recording QOL data in the future may help to evaluate the real benefit of using
      QOL scales in daily practice.

PMID- 28457683
TI  - [Epidemiology and natural history of giant cell arteritis].
AB  - Knowledge of the natural history and epidemiology of giant cell arteritis (GCA)
      is growing. With the recent conceptual change, GCA is no longer considered a
      disease with mandatory cranial symptoms but, rather, a larger disease spectrum
      also including idiopathic aortitis in people older than 50 and polymyalgia
      rheumatica with large-vessel involvement. The incidence peak between age 70 and
      80 years, greater frequency in females and greater occurrence in Nordic countries
      are well-established epidemiological characteristics. Conversely, the notion that
      the incidence of GCA is increasing is challenged by several recent population
      based studies suggesting a trend reversal for about 15 to 20 years. The known
      link with the allele HLA-DRB1*04 was confirmed by a genome-wide association study
      that also found associations with two other genetic polymorphisms. Recent studies
      indicating a link with varicella zoster virus infection have invigorated the
      hypothesis of an infectious cause for GCA. Smoking is the most solidly recognized
      environmental risk factor, but other traditional cardiovascular risk factors do
      not seem to predispose to GCA. Evidence is mounting that overall mortality in GCA
      patients is at best slightly higher than expected in relation to general
      population mortality data, but GCA is associated with an increase in morbidity
      and mortality specifically related to aortic aneurysm or other cardiovascular
      causes. Further studies are needed to integrate the current knowledge into a
      single etiological model.

PMID- 28457684
TI  - [Classification and therapeutic management of monoclonal gammopathies of renal
      significance].
AB  - Two categories of renal disorders associated with monoclonal gammopathies are to
      be distinguished, according to the characteristics of the underlying B-cell
      clone. The first group of renal diseases always occurs in the setting of high
      tumor mass with production of large amounts of monoclonal immunoglobulins. The
      main complication is the so-called myeloma cast nephropathy, which almost
      invariably complicates high tumor mass myeloma. The second group includes all
      renal disorders caused by a monoclonal immunoglobulin secreted by a nonmalignant
      B-cell clone, and currently referred as a "monoclonal gammopathy of renal
      significance (MGRS)". This term was introduced to distinguish monoclonal
      gammopathies that are responsible for the development of kidney damage from those
      that are truly benign. The spectrum of renal diseases in MGRS is wide and its
      classification relies on the localization of renal lesions, either glomerular or
      tubular, and on the pattern of ultrastructural organization of immunoglobulin
      deposits. Physicochemical characteristics of the pathogenic monoclonal
      immunoglobulin are probably involved in their propensity to deposit or
      precipitate in the kidney, as illustrated by the high rate of recurrence of each
      specific type after kidney transplantation. Early diagnosis and efficient
      chemotherapy targeting the causal B-cell clone are mandatory to improve renal
      prognosis and patient survival.

PMID- 28457685
TI  - School District Variation in Parental Influence on Underage Drinking Behaviors.
AB  - PURPOSE: We examined the relationship between alcohol-specific and nonalcohol
      specific parental characteristics with occasional alcohol drinking in early
      adolescence and probed potential school district variation. METHODS: A total of
      1,581 fourth and sixth graders (age range: 10-12 years) were ascertained from 17
      elementary schools in a cohort study conducted in northern Taiwan in 2006, with
      three waves of follow-up between 2007 and 2009. Information on alcohol-specific
      and nonalcohol-specific parental attributes was obtained from the first two waves
      of self-administered paper-and-pencil questionnaires; occasional drinking,
      defined by having drunk on three or more occasions in the past year, was assessed
      at fourth wave. School district characteristics were retrieved from official
      statistics and self-report. Multilevel analyses were used to evaluate strength of
      association, with stratification by disadvantaged status of school districts.
      RESULTS: Thirteen percent (95% confidence interval [CI] = 10.1%-15.8%) of young
      adolescents reported to drink occasionally; higher grade level, childhood
      drinking experience, lower parental education, maternal drinking, and positive
      parental attitude toward drinking were significant predictors. Nonalcohol
      parental predictors, including not living with both parents (adjusted odds ratio
      [aOR] = 2.34, 95% CI = 1.21-4.53) and parental involvement/reinforcement (aOR =
      .44; 95% CI = .22-.87), were only significant for the children of
      socioeconomically disadvantaged school districts. As to alcohol-specific parental
      characteristics, the effects of maternal drinking appear more salient in
      socioeconomically advantaged school districts (aOR = 2.63; 95% CI = 1.66-4.18).
      CONCLUSIONS: Alcohol-specific and nonalcohol-specific parental influence may
      operate differentially across school districts sub-grouped by socioeconomic
      attributes. Preventive strategies raising the awareness of underage drinking and
      strengthening parenting skills should be devised and implemented in the
      perspective of social context.

PMID- 28457686
TI  - Preference for Solitude, Social Isolation, Suicidal Ideation, and Self-Harm in
      Adolescents.
AB  - PURPOSE: Social isolation is associated with suicidal ideation (SI) and self-harm
      (SH) among adolescents. However, the association between preference for solitude
      (PfS), SI, and SH is unknown. The prevalence of adolescents who have both of PfS
      and social isolation and the risks for SI and SH among them are also unknown.
      METHODS: Information on PfS, social isolation, SI, and SH was collected in a
      large-scale school-based survey on adolescents, using a self-report
      questionnaire. Associations between PfS, SI, and SH were examined by logistic
      regression analysis. The interactions between PfS and social isolation on SI and
      SH were also investigated. The odds of SI and SH were examined for groups defined
      by presence of PfS and social isolation. RESULTS: Responses from 17,437 students
      (89.3% of relevant classes) were available. After adjusting for demographic
      characteristics and social isolation, PfS was associated with increased odds of
      SI (odds ratio [OR] = 3.1) and SH (OR = 1.9). There was no interaction between
      PfS and social isolation on SI and SH. After adjusting for demographic
      characteristics, the odds for SI (OR = 8.6) and SH (OR = 3.8) were highest among
      adolescents with both PfS and social isolation (8.4% of all respondents).
      CONCLUSIONS: PfS was associated with increased odds of SI and SH in adolescents.
      No interaction effect between PfS and social isolation on SI and SH was found,
      but adolescents with PfS and social isolation had the highest risk for SI and SH.
      Parents and professionals should pay attention to suicide risk in adolescents
      with PfS.

PMID- 28457687
TI  - Sex Differences in the Impact of Thinness, Overweight, Obesity, and Parental
      Height on Adolescent Height.
AB  - PURPOSE: The secular trend of increasing weight may lead to a decline in height
      gain compared with the genetic height potential. The impact of weight on height
      in healthy male and female adolescents compared with their genetic height was
      assessed. METHODS: Height and weight were measured in Israeli adolescent military
      recrutees aged 16-19 years between 1967 and 2013. The study population comprised
      355,229 recrutees for whom parental height measurements were documented. Subjects
      were classified into four body mass index percentile groups according to the U.S.
      Centers for Disease Control and Prevention body mass index percentiles for age
      and sex:<5th (underweight), 5th-49th (low-normal), 50th-84th (high-normal), and
      >=85th (overweight-obese). Short stature was defined as height <= third
      percentile and tall stature as height >= 90th percentile for age and sex.
      RESULTS: Overweight-obese females had a 73% increased risk for short stature
      (odds ratio [OR]: 1.73, 95% confidence interval [CI] = 1.51-1.97, p < .001).
      Conversely, underweight females had a 56% lower risk of short stature (OR: .44,
      95% CI = .28-.70, p = .001) and a twofold increased risk for being tall (OR:
      2.08, 95% CI = 1.86-2.32, p < .001). Overweight-obese males had a 23% increased
      risk of being short (OR: 1.23, 95% CI = 1.10-1.37, p < .001). Underweight females
      were on average 4.1 cm taller than their mid-parental height. CONCLUSIONS:
      Overweight-obese males and females had an increased risk of being short, and
      underweight females were significantly taller compared with their genetic height.
      The significantly increased height among underweight healthy females may reflect
      a potential loss of height gain in overweight-obese females.

PMID- 28457688
TI  - [Gastrointestinal bleeding secondary to cholesterol embolus polyp as the first
      manifestation of primary biliary cirrhosis in an older adult].

PMID- 28457689
TI  - Development of a neuro early mobilisation protocol for use in a neuroscience
      intensive care unit.
AB  - OBJECTIVE: Through evaluation of the literature and working with a team of
      multidisciplinary healthcare providers, our objective was to refine an
      interprofessional Neuro Early Mobilisation Protocol for complex patients in the
      Neuroscience Intensive Care Unit. RESEARCH METHODOLOGY: Using the literature as a
      guide, key stakeholders, from multiple professions, designed and refined a Neuro
      Early Mobilisation Protocol. SETTING: This project took place at a large academic
      medical center in the southeast United States classified as both a Level I Trauma
      Center and Comprehensive Stroke Center. MAIN OUTCOME MEASURES: Goals for protocol
      development were to: (1) simplify the protocol to allow for ease of use, (2) make
      the protocol more generalizable to the patient population cared for in the
      Neuroscience Intensive Care Unit, (3) receive feedback from those using the
      original protocol on ways to improve the protocol and (4) ensure patients were
      properly screened for inclusion and exclusion in the protocol. RESULTS: Using
      expert feedback and the evidence, an evidence-based Neuro Early Mobilisation
      Protocol was created for use with all patients in the Neuroscience Intensive Care
      Unit. CONCLUSION: Future work will consist of protocol implementation and
      evaluation in order to increase patient mobilisation in the Neuroscience
      Intensive Care Unit.

PMID- 28457690
TI  - Nurse and patient factors that influence nursing time in chest tube management
      early after open heart surgery: A descriptive, correlational study.
AB  - PURPOSE: Determine nurse characteristics and patient factors that affect nurses'
      time in managing chest tubes in the first 24-hours of critical-care stay. DESIGN:
      Prospective, descriptive. METHODS: Cardiovascular critical-care nurses and post
      operative heart surgery patients with chest tubes were enrolled from a single
      center in Ohio. Nurses completed case report forms about themselves, comfort and
      time in managing chest tubes, chest tube placement and management factors.
      Analysis included correlational and comparative statistics; Bonferroni
      corrections were applied, as appropriate. RESULTS: Of 29 nurses, 86.2% were very
      comfortable managing chest tubes and oozing/non-secure dressings, but only 41.4%
      were very comfortable managing clogged chest tubes. Of 364 patients, mean age was
      63.1 (+/-12.3) years and 36% had previous heart surgery. Total minutes of chest
      tube management was higher with>=3 chest tubes, tube size <28 French, and when
      both mediastinal and pleural tubes were present (all p<0.001). In the first 4
      hours, time spent on chest tubes was higher when patients had previous cardiac
      surgeries (p<=0.002), heart failure (p<0.001), preoperative anticoagulant
      medications (p=0.031) and reoperation for postoperative bleeding/tamponade
      (p=0.005). CONCLUSIONS: Time to manage chest tubes can be anticipated by patient
      characteristics. Nurse comfort with chest tube-related tasks affected time spent
      on chest tube management.

PMID- 28457691
TI  - Measuring intrinsic hand strength in healthy adults: The accuracy intrarater and
      inter-rater reliability of the Rotterdam Intrinsic Hand Myometer.
AB  - STUDY DESIGN: Clinical measurement study. INTRODUCTION: Measuring the isometric
      strength generated during isolated hand joint motions is a challenging feat. The
      Rotterdam Intrinsic Hand Myometer (RIHM; med.engineers, Rotterdam, Netherlands)
      permits measurement of isolated movements of the hand. To date, there is limited
      evidence on the inter-rater reliability and limited adult normative data of RIHM.
      Given that multiple raters, often with varying degrees of experience, are needed
      to collect normative data, inter-rater reliability testing and a comparison of
      novice and experienced raters are needed. PURPOSES OF THE STUDY: The purposes of
      this study were to test the accuracy, intrarater reliability, and inter-rater
      reliability of the RIHM in healthy-handed adults. METHODS: RIHM accuracy was
      tested through use of precision class F weights. Adults 18 years or older without
      upper limb dysfunction were recruited. Each participant was tested by 4 raters, 3
      occupational therapy graduate students, and an experienced certified hand
      therapist, through use of a calibrated RIHM. Five strength measures were tested
      bilaterally (ie, thumb carpometacarpal palmar abduction, index finger
      metacarpophalangeal [MP] abduction, index finger MP flexion, thumb MP flexion,
      and small finger MP abduction) 3 times per a standardized protocol. Statistical
      methods were used to test accuracy, inter-rater reliability, and
      intrarater/response stability. RESULTS: The accuracy of RIHM device error was 5%
      or less. Reliability testing included the participation of 19 women and 10 men (n
      = 29). All raters were in excellent agreement across all muscles (intraclass
      correlation coefficient, >=0.81). Low standard error of measurement values of
      <=8.3 N (1.9 lb) across raters were found. The response stability and/or
      intrarater reliability of the novice and certified hand therapist raters were not
      statistically different. DISCUSSION: The RIHM has an acceptable instrument error;
      the RIHM and its standardized procedure have excellent inter-rater reliability
      and response stability when testing those without hand limitations; and the
      response stability and/or intrarater reliability of expert and novice raters were
      consistent. CONCLUSIONS: The use of the RIHM is justified when multiple raters of
      varying expertise collect normative data or conduct cohort studies on persons
      with healthy hands. Future research is warranted. LEVEL OF EVIDENCE: Not
      applicable.

PMID- 28457692
TI  - Is Pregnancy-Associated Melanoma Associated with Adverse Outcomes?
AB  - BACKGROUND: Melanoma is the most common malignancy encountered during pregnancy.
      Conflicting data have led to ongoing confusion regarding pregnancy-associated
      melanoma (PAM) in the media and among the public. The objective of this study was
      to better characterize both the clinical presentation of PAM and its prognostic
      implications. STUDY DESIGN: Female patients of reproductive age, with stage 0 to
      IV cutaneous melanoma, were identified from our prospectively maintained
      database. Clinical and histopathologic factors were analyzed with appropriate
      statistical methods. Univariable and then multivariable analysis were used on
      matched data to compare disease-free survival (DFS), overall survival (OS), and
      melanoma-specific survival (MSS) for stage 0-III PAMs vs non-PAMs. Kaplan-Meier
      survival curves were then plotted for OS and MSS and compared using the log-rank
      test. RESULTS: The clinical presentation of melanoma was similar for PAM and non
      PAM patients. There was no significant difference in recurrence between the 2
      groups; for PAM patients, 38.5% of patients had recurrence, as compared with
      36.6% of non-PAM patients (p = 0.641). For PAM patients, median follow-up was
      14.6 years (range 0 to 42.6 years) and 11.1 years (0 to 48.5 years) for the non
      PAM patients. No significant differences in DFS, MSS, or OS were identified on
      univariable or multivariable analysis for PAM vs non-PAM patients in stage 0/I/II
      and stage III cutaneous melanoma, respectively (p = 0.880 DFS, p = 0.219 OS, and
      p = 0.670 MSS). CONCLUSIONS: We observed no difference in DFS, OS, or MSS between
      the 2 groups. Pregnant patients should be screened for melanoma in a similar
      manner to nonpregnant patients and should be counseled that their survival is not
      adversely affected by their pregnancy.

PMID- 28457693
TI  - Antioxidant and anticholinesterase potential of diterpenoid alkaloids from
      Aconitum heterophyllum.
AB  - Extensive chromatographic separations performed on the basic (pH=8-10) chloroform
      soluble fraction of Aconitum heterophyllum resulted in the isolation of three new
      diterpenoid alkaloids, 6beta-Methoxy, 9beta-dihydroxylheteratisine (1),
      1alpha,11,13beta-trihydroxylhetisine (2), 6,15beta-dihydroxylhetisine (3), and
      the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi
      isoatisine (7), and atidine (8). Structures of the isolated compounds were
      established by means of mass and NMR spectroscopy as well as single crystal X-ray
      crystallography. Compounds 1-8 were screened for their antioxidant and enzyme
      inhibition activities followed by in silico studies to find out the possible
      inhibitory mechanism of the tested compounds. This work is the first report
      demonstrating significant antioxidant and anticholinesterase potentials of
      diterpenoid alkaloids isolated from a natural source.

PMID- 28457694
TI  - A rare form of Gaucher disease resulting from saposin C deficiency.
AB  - Gaucher disease is mainly caused by the deficiency of lysosomal acid beta
      glucosidase. Gaucher disease caused by the deficiency of saposin C is rare. Here
      we report a patient mainly presenting with hepatosplenomegaly, thrombocytopenia
      and anemia. EEG examination revealed increased theta waves. Gaucher cells
      identified in his bone marrow and the highly elevated plasma chitotriosidase
      activity and glucosylsphingosine supported a diagnosis of Gaucher disease.
      However, the leukocyte beta-glucosidase activity was in a normal range. Sanger
      sequencing revealed a novel maternal exonic mutation c.1133C>G (p.Pro378Arg) in
      exon 10 of the PSAP gene, which codes the Sap C domain of PSAP protein. To search
      for other underlying mutations in this patient, whole genome sequencing was
      applied and revealed a deletion involving exon 2 to 7 of PSAP gene. The deletion
      appears as a de novo event on paternal chromosome. We concluded that biallelic
      mutations of PSAP gene were the cause of this patient's Gaucher disease. Our
      finding expands the mutation spectrum of Gaucher disease with saposin C
      deficiency.

PMID- 28457695
TI  - Using Technology to Reduce Childrens' Anxiety Throughout the Perioperative
      Period.

PMID- 28457698
TI  - Cajita MA, Denhaerynck K, Dobbels F, Berben L, Russell CL, Davidson PM. Health
      literacy in heart transplantation: Prevalence, correlates and associations with
      health behaviors-Findings from the international BRIGHT study. J Heart Lung
      Transplant 2017;36(3):272-79.

PMID- 28457696
TI  - Numerous Ontogenetic Roads to Mantle Cell Lymphoma: Immunogenetic and
      Immunohistochemical Evidence.
AB  - To obtain insight into the ontogeny of mantle cell lymphoma (MCL), we assessed
      206 patients from a morphological, immunohistochemical, and immunogenetic
      perspective. Our series included nodal (n = 151), extranodal (n = 28), and
      primary splenic (n = 27) MCL cases. Skewing of the immunoglobulin heavy variable
      (IGHV) gene repertoire was noted, with only four IGHV genes accounting for 46% of
      cases and approximately 70% of cases (107/154) bearing an imprint of somatic
      hypermutation (SHM) ranging from minimal to pronounced. Interestingly, a
      distinctive immunophenotypic and immunogenetic profile was identified for primary
      splenic MCL, which was enriched for DBA.44-positive cases (P < 0.001) and used
      the IGHV1-8 gene more frequently (P = 0.02) compared to nodal or extranodal
      cases, alluding to distinct immunopathogenetic and antigen selection processes.
      Expression of CD27 (considered a marker of activated B cells) was generally
      dissociated from SHM and was more prevalent in cases with no or
      minimal/borderline SHM. These findings support the idea that antigen drive is
      relevant for most MCL cases, although the specific antigens and the precise
      location of affinity maturation remain to be elucidated. Moreover, they raise the
      intriguing hypothesis of multiple cellular origins for MCL.

PMID- 28457697
TI  - Extended distance cardiac allograft can successfully be utilized without
      impacting long-term survival.
AB  - BACKGROUND: Despite the severe shortage of donor cardiac allografts, the general
      belief in worse outcomes with donors from prolonged distances has resulted in
      many centers greatly limiting the acceptable geographic distance of acceptable
      donors. However, with improvements in allograft preservation, it is likely that
      distance may be extended without compromising graft integrity. We hypothesized
      that recipients of appropriately selected allografts from greater distances would
      have equivalent long-term survival compared with recipients from closer
      geographic regions. METHODS: We retrospectively analyzed the United Network for
      Organ Sharing (UNOS) adult heart transplant data from January 2000 to December
      2013. Recipients were stratified by donor distance. Demographic and outcomes data
      were analyzed, with a primary end-point of survival. RESULTS: During the study
      period, 25,996 isolated orthotopic heart transplantations (OHTs) were performed.
      Patients were stratified by distance: 0 to 500 miles (n = 24,645); 501 to 1,000
      miles (n = 1,201); 1,001 to 1,500 miles (n = 134); and 1,501+ miles (n = 16).
      Increased donor allograft distance correlated with significantly longer ischemic
      times (3.1 miles for 0 to 500 miles vs 7.5 hours for 1,501+ miles, p = 0.0001).
      One- and 5-year survival was similar in all cohorts, using Kaplan-Meier survival
      analysis (log rank, p = 0.8025). There was no difference in rate of stroke (p =
      0.82), dialysis (p = 0.60) or reoperation (p = 0.28). Length of stay was
      equivalent across cohorts (p = 0.11). CONCLUSIONS: Appropriately selected
      allografts from donors at a greater distance should be considered to increase
      organ availability. Donor heart procurement from increased distance may not
      directly increase morbidity and mortality post-heart transplant.

PMID- 28457699
TI  - Erratum.

PMID- 28457700
TI  - Human Connexin40 Mutations Slow Conduction and Increase Propensity for Atrial
      Fibrillation.
AB  - BACKGROUND: Patch clamping studies using non-cardiomyocytes revealed that the
      human connexin40 mutations P88S, G38D, and A96S are associated with reduced gap
      junction conductances compared to wild type connexin40 (wtCx40). Their effects
      within myocytes however are unclear. We aimed to characterise P88S, G38D, and
      A96S after expression in rat hearts and primary cardiomyocyte cultures. METHODS:
      Adult Sprague-Dawley rat atria were transduced with a lentivector containing a
      transgene encoding wtCx40, P88S, G38D, A96S, or eGFP (n=6 per transgene).
      Electrophysiology studies (EPS) were performed just prior to and 7 days after
      surgery. Left atria were assessed for connexin expression, mRNA levels,
      inflammation and fibrosis. Primary cardiomyocyte cultures were also transduced
      with the abovementioned vectors (n=6 per transgene) and monolayer conduction
      velocities (CV) and protein expression were assessed at 96hours. RESULTS: At day
      7 EPS, P wave and induced atrial fibrillation (AF) durations were significantly
      longer in the mutant groups when compared to wtCx40 controls (p<0.05). There were
      no significant differences in inflammation, fibrosis, or heart to body weight
      ratios. Monolayer CV's were reduced in the A96S group compared to the wtCx40
      group. While similar to wtCx40 controls, P88S velocities were reduced compared to
      eGFP controls. G38D monolayers possessed spontaneous fibrillatory activity and
      could not be paced. Immunofluorescence revealed that P88S and G38D reduced native
      connexin43 myocyte coupling while A96S appeared to co-localise with connexin43 in
      gap junctions. Connexin43 mRNA levels were similar between groups. CONCLUSIONS:
      The A96S, G38D, and P88S Cx40 mutations slow conduction and increased the
      propensity for inducible AF.

PMID- 28457701
TI  - Primary care physician management of tick bites in the Franche-Comte region
      (Eastern France, 2013).
AB  - INTRODUCTION: Tick bites, which may lead to Lyme disease, often prompt patients
      to consult their primary care physicians (PCPs). The aim of the present study was
      to assess how and how often PCPs in the Franche-Comte region of France manage
      tick bites. MATERIAL AND METHODS: Standardized questionnaires were sent to a
      random sample of 400 PCPs in the Franche-Comte region, requesting their voluntary
      and anonymous participation. The questionnaires collected socio-demographic
      details and practice-related information about tick-bite prophylaxis, Lyme
      serology, and tick-borne encephalitis vaccination. RESULTS: The crude response
      rate was 54.5% of the PCPs contacted. Tick-bite prophylaxis was prescribed as per
      current guidelines. However, Lyme serology seemed to be largely overprescribed
      for tick bites and in case of erythema migrans. A clear lack of knowledge about
      tick-borne encephalitis vaccination was also observed. DISCUSSION: PCPs provide
      the first line of care for patients presenting with tick bites. This study showed
      that although PCPs of the Franche-Comte region manage tick bites as per current
      guidelines, they need further training on Lyme serology limitations and
      availability of tick-borne encephalitis vaccination.

PMID- 28457702
TI  - Medical table: A major tool for antimicrobial stewardship policy.
AB  - Infectious diseases are unpredictable, with heterogeneous clinical presentations,
      diverse pathogens, and various susceptibility rates to anti-infective agents.
      These features lead to a wide variety of clinical practices, which in turn
      strongly limits their evaluation. We have been using a medical table since 2005
      to monitor the medical activity in our department. The observation of
      heterogeneous therapeutic practices led to drafting up our own antibiotic
      guidelines and to implementing a continuous evaluation of their observance and
      impact on morbidity and mortality associated with infectious diseases, including
      adverse effects of antibiotics, duration of hospital stay, use of intensive care,
      and deaths. The 10-year analysis of medical practices using the medical table is
      based on more than 10,000 hospitalizations. It shows simplified antibiotic
      therapies and a reduction in infection-related morbidity and mortality. The
      medical table is a major tool for antimicrobial stewardship, leading to constant
      benefits for patients.

PMID- 28457703
TI  - Diabetic complications do not hamper improvement of health-related quality of
      life over the course of treatment of diabetic foot ulcers - the Eurodiale study.
AB  - AIMS: Diabetic complications, and in particular diabetic foot ulcers (DFUs), are
      associated with low health-related quality of life (HRQoL). We evaluated whether
      the presence of diabetic complications also influenced the improvement of HRQoL
      during DFU treatment. METHODS: 1088 patients presenting for DFU treatment at the
      centers participating in the Eurodiale study were followed prospectively up to
      one year. HRQoL was measured both at presentation and after healing or at end of
      follow up, using EQ-5D: a standardized instrument consisting of five domains and
      a summary index. The influence of diabetic comorbidity on the course of HRQoL was
      evaluated for each of the EQ-5D outcomes in multi-level linear regression
      analyses, adjusting for baseline characteristics. RESULTS: HRQoL improved in all
      EQ-5D outcomes over the course of treatment for those DFUs that healed. The few
      significant differences in the development of HRQoL between patients with and
      without comorbidity showed a more beneficial development for patients with
      comorbidity in DFUs that did not heal or healed slowly. CONCLUSIONS: Comorbidity
      does not hamper improvement of HRQoL in DFU treatment. On the contrary, HRQoL
      improved sometimes more in patients with certain comorbidity with hard-to-heal
      ulcers.

PMID- 28457704
TI  - NADPH oxidase p22phox C242T polymorphism is associated with macroalbuminuria in
      diabetic patients: A meta-analysis.
AB  - AIMS: Previous studies suggested an association between C242T polymorphism in
      NADPH Oxidase p22phox and diabetic nephropathy (DN) risk, but the results were
      inconsistent. To obtain a more precise estimation, we carried out a meta-analysis
      to analyze the effect of C242T polymorphism in NADPH Oxidase p22phox on DN risk.
      METHODS: We searched PubMed, ISI Web of Science, and China National Knowledge
      Infrastructure for all eligible case-control studies through May 2016. The odds
      ratios (ORs), together with the 95% confidence intervals (CIs), were calculated
      to evaluate the strength of association between C242T SNP in NADPH Oxidase
      p22phox on DN risk. RESULTS: Overall, ten eligible studies involving a total of
      1894 cases and 1746 controls were included in our meta-analysis. The results
      showed that there was no statistical evidence of association between NADPH
      oxidase p22phox C242T polymorphism and DN in all genetic models (T vs. C: OR
      1.16, 95% CI 0.85-1.59, p=0.34; TT vs. CC: OR 1.49, 95% CI 0.80-2.76, p=0.21;
      TT/CT vs. CC: OR 1.18, 95% CI 0.81-1.72, p=0.40; TT vs. CT/CC: OR 1.31, 95% CI
      0.82-2.11, p=0.26). However, significant association was found in diabetic
      patients with macroalbuminuria. CONCLUSION: This meta-analysis indicates that
      NADPH oxidase p22phox C242T polymorphism is associated with macroalbuminuria in
      diabetic patients. However, this conclusion should be interpreted with caution
      due to the small sample size. Larger sample-size studies with homogeneous
      patients and well-matched controls are required.

PMID- 28457706
TI  - A Versatile Tool for Live-Cell Imaging and Super-Resolution Nanoscopy Studies of
      HIV-1 Env Distribution and Mobility.
AB  - The envelope glycoproteins (Env) of HIV-1 mediate cell entry through fusion of
      the viral envelope with a target cell membrane. Intramembrane mobility and
      clustering of Env trimers at the viral budding site are essential for its
      function. Previous live-cell and super-resolution microscopy studies were limited
      by lack of a functional fluorescent Env derivative, requiring antibody labeling
      for detection. Introduction of a bio-orthogonal amino acid by genetic code
      expansion, combined with click chemistry, offers novel possibilities for site
      specific, minimally invasive labeling. Using this approach, we established
      efficient incorporation of non-canonical amino acids within HIV-1 Env in
      mammalian cells. The engineered protein retained plasma membrane localization,
      glycosylation, virion incorporation, and fusogenic activity, and could be rapidly
      and specifically labeled with synthetic dyes. This strategy allowed us to revisit
      Env dynamics and nanoscale distribution at the plasma membrane close to its
      native state, applying fluorescence recovery after photo bleaching and STED
      nanoscopy, respectively.

PMID- 28457705
TI  - Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin
      A.
AB  - Protein synthesis plays an essential role in cell proliferation, differentiation,
      and survival. Inhibitors of eukaryotic translation have entered the clinic,
      establishing the translation machinery as a promising target for chemotherapy. A
      recently discovered, structurally unique marine sponge-derived brominated
      alkaloid, (-)-agelastatin A (AglA), possesses potent antitumor activity. Its
      underlying mechanism of action, however, has remained unknown. Using a systematic
      top-down approach, we show that AglA selectively inhibits protein synthesis.
      Using a high-throughput chemical footprinting method, we mapped the AglA-binding
      site to the ribosomal A site. A 3.5 A crystal structure of the 80S eukaryotic
      ribosome from S. cerevisiae in complex with AglA was obtained, revealing multiple
      conformational changes of the nucleotide bases in the ribosome accompanying the
      binding of AglA. Together, these results have unraveled the mechanism of
      inhibition of eukaryotic translation by AglA at atomic level, paving the way for
      future structural modifications to develop AglA analogs into novel anticancer
      agents.

PMID- 28457707
TI  - Mitochondrial Chaperonin HSP60 Is the Apoptosis-Related Target for
      Myrtucommulone.
AB  - The acylphloroglucinol myrtucommulone A (MC) causes mitochondrial dysfunctions by
      direct interference leading to apoptosis in cancer cells, but the molecular
      targets involved are unknown. Here, we reveal the chaperonin heat-shock protein
      60 (HSP60) as a molecular target of MC that seemingly modulates HSP60-mediated
      mitochondrial functions. Exploiting an unbiased, discriminative protein fishing
      approach using MC as bait and mitochondrial lysates from leukemic HL-60 cells as
      target source identified HSP60 as an MC-binding protein. MC prevented HSP60
      mediated reactivation of denatured malate dehydrogenase in a protein refolding
      assay. Interference of MC with HSP60 was accompanied by aggregation of two
      proteins in isolated mitochondria under heat shock that were identified as Lon
      protease-like protein (LONP) and leucine-rich PPR motif-containing protein
      (LRP130). Together, our results reveal HSP60 as a direct target of MC, proposing
      MC as a valuable tool for studying HSP60 biology and for evaluating its value as
      a target in related diseases, such as cancer.

PMID- 28457709
TI  - Pregnancy complications in survivors of childhood cancer.

PMID- 28457710
TI  - Can post-polypectomy surveillance be less intensive?

PMID- 28457711
TI  - European Association for the Study of the Liver: International Liver Congress
      2017 Meeting.

PMID- 28457708
TI  - Adenoma surveillance and colorectal cancer incidence: a retrospective,
      multicentre, cohort study.
AB  - BACKGROUND: Removal of adenomas reduces colorectal cancer incidence and
      mortality; however, the benefit of surveillance colonoscopy on colorectal cancer
      risk remains unclear. We examined heterogeneity in colorectal cancer incidence in
      intermediate-risk patients and the effect of surveillance on colorectal cancer
      incidence. METHODS: We did this retrospective, multicentre, cohort study using
      routine lower gastrointestinal endoscopy and pathology data from patients who,
      after baseline colonoscopy and polypectomy, were diagnosed with intermediate-risk
      adenomas mostly (>99%) between Jan 1, 1990, and Dec 31, 2010, at 17 hospitals in
      the UK. These patients are currently offered surveillance colonoscopy at
      intervals of 3 years. Patients were followed up through to Dec 31, 2014.We
      assessed the effect of surveillance on colorectal cancer incidence using Cox
      regression with adjustment for patient, procedural, and polyp characteristics. We
      defined lower-risk and higher-risk subgroups on the basis of polyp and procedural
      characteristics identified as colorectal cancer risk factors. We estimated
      colorectal cancer incidence and standardised incidence ratios (SIRs) using as
      standard the general population of England in 2007. This trial is registered,
      number ISRCTN15213649. FINDINGS: 253 798 patients who underwent colonic endoscopy
      were identified, of whom 11 944 with intermediate-risk adenomas were included in
      this analysis. After a median follow-up of 7.9 years (IQR 5.6-11.1), 210
      colorectal cancers were diagnosed. 5019 (42%) patients did not attend
      surveillance and 6925 (58%) attended one or more surveillance visits. Compared to
      no surveillance, one or two surveillance visits were associated with a
      significant reduction in colorectal cancer incidence rate (adjusted hazard ratio
      0.57, 95% CI 0.40-0.80 for one visit; 0.51, 0.31-0.84 for two visits). Without
      surveillance, colorectal cancer incidence in patients with a suboptimal quality
      colonoscopy, proximal polyps, or a high-grade or large adenoma (>=20 mm) at
      baseline (8865 [74%] patients) was significantly higher than in the general
      population (SIR 1.30, 95% CI 1.06-1.57). By contrast, in patients without these
      features, colorectal cancer incidence was lower than that of the general
      population (SIR 0.51, 95% CI 0.29-0.84). INTERPRETATION: Colonoscopy surveillance
      benefits most patients with intermediate-risk adenomas. However, some patients
      are already at low risk after baseline colonoscopy and the value of surveillance
      for them is unclear. FUNDING: National Institute for Health Research Health
      Technology Assessment, Cancer Research UK.

PMID- 28457712
TI  - Treatment options for early-stage Hodgkin's lymphoma.

PMID- 28457713
TI  - Management of Helicobacter Pylori in the United States: Results from a national
      survey of gastroenterology physicians.
AB  - BACKGROUND AND AIMS: We sought to determine current knowledge and practices among
      gastroenterology physicians and assess adherence to current guidelines for H.
      pylori management. METHODS: Online surveys were distributed in 2014 to practicing
      gastroenterology physicians for information related to the diagnosis and
      treatment of H. pylori infection. RESULTS: A total of 582 completed surveys were
      reviewed. The H. pylori screening test used "almost always" was gastric biopsy
      obtained during endoscopy (histology) (59%) followed by stool antigen test (20%).
      Standard triple therapy for 14days was commonly prescribed by 53% of respondents.
      The stool antigen test was most frequently chosen to confirm H. pylori
      eradication (51%), although only 58% of physicians checked for eradication in
      patients who underwent treatment. CONCLUSIONS: Adherence to current American
      College of Gastroenterology guidelines is low. Although more physicians treat
      patients with a positive H. pylori test, only half ensure eradication after
      treatment. Improving knowledge of the resistance patterns of H. pylori may be
      critical to ensure successful eradication.

PMID- 28457714
TI  - Discouraging soft drink consumption reduces blood glucose and cholesterol of
      Brazilian elementary students: Secondary analysis of a randomized controlled
      trial.
AB  - The objective of this study was to evaluate the effect of an educational program
      aimed at discouraging sugar-sweetened carbonated beverages intake on blood
      fasting glucose and total cholesterol. Forty-seven fourth grade classes in twenty
      two schools have participated in a randomized controlled trial aimed at
      discouraging soft drink intake in order to prevent excessive weight gain during a
      school year, in the city of Niteroi, Rio de Janeiro. Of 1140 randomized students,
      478 (238 in intervention group and 240 in control group) aged 9-12years old had
      at least one result on biochemical data and were analyzed to evaluate the effect
      of the intervention on changes in fasting glucose and total cholesterol at the
      end of follow-up. Intention-to-treat analysis was performed taking into account
      the cluster (classes) effect. Statistically significant decrease in fasting
      glucose (-9.12mg/dL vs. +0.51mg/dL, p<0.001) and total cholesterol (-10.34mg/dL
      vs. +2.14mg/dL, p<0.001) were observed among students in the intervention group
      in comparison with controls. In addition, the prevalence of impaired fasting
      glucose and hypercholesterolemia decreased in interventions and increased in
      controls (-2.4% vs. +8.8%, p=0.04 and -10.0% vs. +2.7%, p=0.03, respectively).
      Discouraging soft drink consumption among children has led to a reduction in
      fasting glucose and total cholesterol, suggesting that these beverages may play a
      role in the development of cardiometabolic risk in childhood.

PMID- 28457716
TI  - [An analysis of 51.996 online opinions in a commercial rating website].

PMID- 28457715
TI  - Feeding and Mealtime Correlates of Maternal Concern About Children's Weight.
AB  - OBJECTIVE: To examine associations between maternal concern regarding their
      children becoming overweight and two domains of weight-related parenting; child
      feeding practices and family meal characteristics. DESIGN: Cross-sectional study.
      PARTICIPANTS: Low-income mothers (n = 264; 67% non-Hispanic white) and their
      children (51.5% male, aged 4.02-8.06 years). VARIABLES MEASURED: Maternal concern
      and feeding practices, using the Child Feeding Questionnaire. Meal
      characteristics were assessed using video-recorded meals and meal information
      collected from mothers. ANALYSIS: The authors used MANOVA and logistic regression
      to identify differences in maternal feeding practices and family meal
      characteristics across levels of maternal concern (none, some, and high).
      RESULTS: Approximately half of mothers were not concerned about their child
      becoming overweight, 28.4% reported some concern, and 19.0% had high concern.
      Mothers reporting no concern described lower restrictive feeding compared with
      mothers who reported some or high concern (mean [SE], none = 3.1 [0.1]; some =
      3.5 [0.1]; and high = 3.6 [0.1]; P = .004). No differences in other feeding
      practices or family meal characteristics were observed by level of concern.
      CONCLUSIONS AND IMPLICATIONS: Concern regarding children becoming overweight was
      common. However, concern rarely translated into healthier feeding practices or
      family meal characteristics. Maternal concern alone may not be sufficient to
      motivate action to reduce children's risk of obesity.

PMID- 28457717
TI  - Infantile hemangioma: Predicting proliferation by infrared thermography.
AB  - BACKGROUND AND OBJECTIVE: Infantile hemangiomas (IHs) are benign lesions found in
      infants. Predicting the cosmetic outcome of these lesions is very difficult.
      Therefore, in this prospective study, we assessed whether using an infrared
      thermometer (IRT) to measure the surface temperature of IHs would help to predict
      their proliferative potential. MATERIALS AND METHODS: Between January 2012 and
      March 2014, we prospectively investigated 103 children up to 6 months of age with
      a diagnosis of IH. None of them required immediate treatment. Two projection
      plain photographs of the IHs were obtained and the temperature of the IH surface
      was measured with the IRT at each visit. The IHs in these patients were divided
      into three groups: stable, slightly growing and growing IHs. We analyzed
      temperature differences between the groups, relative operating characteristic
      (ROC) curves, and possible application of this method to clinical practice.
      RESULTS: The median initial temperatures in the groups were 36.7 degrees C for
      the stable group, 37 degrees C for the slightly growing group, and 37.4 degrees C
      for the growing group (P<0.01). The area under the ROC curve for the temperature
      values to predict growth was 0.929. Temperatures at or above 37.4 degrees C
      showed a specificity of 95%, a sensitivity of 75%, a positive predictive value
      81%, and a negative predictive value of 95%. CONCLUSIONS: IRT is a time and cost
      effective tool, and is easy to learn. The surface temperature of IH reflects its
      remaining growth potential and could be used in the outpatient setting for the
      evaluation and follow-up of IH.

PMID- 28457718
TI  - The effect of galsulfase enzyme replacement therapy on the growth of patients
      with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).
AB  - Mucopolysaccharidosis (MPS) VI is an autosomal recessive lysosomal storage
      disorder arising from deficient activity of N-acetylgalactosamine-4-sulfatase
      (arylsulfatase B) and subsequent intracellular accumulation of the
      glycosaminoglycans (GAGs) dermatan sulfate and chondroitin-4-sulfate.
      Manifestations are multi-systemic and include skeletal abnormalities such as
      dysostosis multiplex and short stature. Reference height-for-age growth charts
      for treatment-naive MPS VI patients have been published for both the slowly and
      rapidly progressing populations. Categorization of disease progression for these
      charts was based on urinary GAG (uGAG) level; high (>200MUg/mg creatinine) levels
      identified subjects as rapidly progressing. Height data for 141 patients who
      began galsulfase treatment by the age of 18years were collected and stratified by
      baseline uGAG level and age at ERT initiation in 3-year increments. The reference
      MPS VI growth charts were used to calculate change in Z-score from pre-treatment
      baseline to last follow-up. Among patients with high baseline uGAG levels,
      galsulfase ERT was associated with an increase in Z-score for those beginning
      treatment at 0-3, >3-6, >6-9, >9-12, and >12-15years of age (p<0.05). Increases
      in Z-score were not detected for patients who began treatment between 15 and
      18years of age, nor for patients with low (<=200MUg/mg creatinine) baseline uGAG
      levels, regardless of age at treatment initiation. The largest positive deviation
      from untreated reference populations was seen in the high uGAG excretion groups
      who began treatment by 6years of age, suggesting an age- and severity-dependent
      impact of galsulfase ERT on growth.

PMID- 28457719
TI  - Crystal structure of a mutant glycosylasparaginase shedding light on
      aspartylglycosaminuria-causing mechanism as well as on hydrolysis of non
      chitobiose substrate.
AB  - Glycosylasparaginase (GA) is an amidase that cleaves Asn-linked glycoproteins in
      lysosomes. Deficiency of this enzyme causes accumulation of glycoasparagines in
      lysosomes of cells, resulting in a genetic condition called
      aspartylglycosaminuria (AGU). To better understand the mechanism of a disease
      causing mutation with a single residue change from a glycine to an aspartic acid,
      we generated a model mutant enzyme at the corresponding position (named G172D
      mutant). Here we report a 1.8A resolution crystal structure of mature G172D
      mutant and analyzed the reason behind its low hydrolase activity. Comparison of
      mature G172D and wildtype GA models reveals that the presence of Asp 172 near the
      catalytic site affects substrate catabolism in mature G172D, making it less
      efficient in substrate processing. Also recent studies suggest that GA is capable
      of processing substrates that lack a chitobiose (Glycan, N-acetylchiobios,
      NAcGlc) moiety, by its exo-hydrolase activity. The mechanism for this type of
      catalysis is not yet clear. l-Aspartic acid beta-hydroxamate (beta-AHA) is a non
      chitobiose substrate that is known to interact with GA. To study the underlying
      mechanism of non-chitobiose substrate processing, we built a GA-beta-AHA complex
      structure by comparing to a previously published G172D mutant precursor in
      complex with a beta-AHA molecule. A hydrolysis mechanism of beta-AHA by GA is
      proposed based on this complex model.

PMID- 28457720
TI  - Quantitative Analysis of the Transporter-Mediated Drug-Drug Interaction Between
      Atorvastatin and Rifampicin Using a Stable Isotope-IV Method.
AB  - This study aims to investigate the drug-drug interactions (DDIs) between orally
      administered atorvastatin (ATV) and rifampicin (RIF) in rats. The isotope-IV
      method was used for the analysis of the increased systemic exposure (AUCpo) of
      ATV, in which a small amount of deuterium-labeled ATV (ATV-d5) was intravenously
      injected after oral administration of ATV. By assuming ATV-d5 showed same
      pharmacokinetic properties with ATV, this method enabled to calculate the
      systemic clearance (CLtot) and the oral bioavailability (Foral) of ATV for each
      individual rat in a single experiment. RIF was orally pretreated to rats to
      inhibit the organic anion transporting polypeptide 1B1 (OATP1B1). From the
      analysis using pharmacokinetic parameters in each rat, it was revealed that the
      AUCpo of ATV increased depending on the plasma level of RIF, showing that the
      interindividual difference in the absorption of RIF caused the large variability
      in the extent of DDI. Furthermore, it was indicated that not only the decrease in
      CLtot but also the increase in Foral caused the significant increase in the AUCpo
      of ATV. In conclusion, the isotope-IV method possesses various advantages over
      the conventional method for the analysis of DDIs which affects both absorption
      and elimination processes of oral drugs.

PMID- 28457721
TI  - Improvement of outdoor culture efficiency of cyanobacteria by over-expression of
      stress tolerance genes and its implication as bio-refinery feedstock.
AB  - This study was undertaken to increase the biomass and carbohydrate productivities
      of a freshwater cyanobacterium Synechococcus elongatus under hot outdoor
      conditions through genetic manipulation to facilitate the application of using
      the cyanobacterial biomass as bio-refinery feedstocks. The stress tolerance genes
      (hspA, osmotin) were expressed in S. elongatus to improve their growth under
      various environment stresses of outdoor cultivation. The results revealed that
      over-expression of hspA and osmotin significantly improved temperature (45
      degrees C), high light intensity, and salt tolerances of S. elongatus cells,
      making it capable of efficiently growing in seawater under outdoor cultivation.
      The carbohydrate productivity of these stress tolerant strains was also 15-30
      fold higher than that of the control strain, although the carbohydrate contents
      of the recombinant and control strains were similar. Our findings demonstrate
      that the genetic engineering for improved stresses tolerance in S. elongatus
      could facilitate the feasibility of using cyanobacteria as feedstock for bio
      refinery industry.

PMID- 28457722
TI  - Lower pressure heating steam is practical for the distributed dry dilute sulfuric
      acid pretreatment.
AB  - Most studies paid more attention to the pretreatment temperature and the resulted
      pretreatment efficiency, while ignored the heating media and their scalability to
      an industry scale. This study aimed to use a relative low pressure heating steam
      easily provided by steam boiler to meet the requirement of distributed dry dilute
      acid pretreatment. The results showed that the physical properties of the
      pretreated corn stover were maintained stable using the steam pressure varying
      from 1.5, 1.7, 1.9 to 2.1MPa. Enzymatic hydrolysis and high solids loading
      simultaneous saccharification and fermentation (SSF) results were also
      satisfying. CFD simulation indicated that the high injection velocity of the low
      pressure steam resulted in a high steam holdup and made the mixing time of steam
      and solid corn stover during pretreatment much shorter in comparison with the
      higher pressure steam. This study provides a design basis for the boiler
      requirement in distributed pretreatment concept.

PMID- 28457723
TI  - Dosimetric effect of multileaf collimator leaf width on volumetric modulated arc
      stereotactic radiotherapy for spine tumors.
AB  - This work aimed to study the dosimetric effect of multileaf collimator (MLC) leaf
      widths in treatment plans for patients receiving volumetric modulated arc therapy
      (VMAT) for spine stereotactic body radiation therapy (SBRT). Thirteen patients
      treated with spine SBRT were retrospectively selected for this study. The
      patients were treated following the protocol of the Radiation Therapy Oncology
      Group 0631 (RTOG 0631) for spine metastasis. The prescription dose was 16 Gy in 1
      fraction to 90% of the target volume (V16 > 90%). The maximum spinal cord dose of
      14 Gy and 10% of the spinal cord receiving < 10 Gy (V10) were the acceptable
      tolerance doses. For the purpose of this study, 2 dual-arc VMAT plans were
      created for each patient using 3 different MLC leaf widths: 2.5 mm, 4 mm, and 5
      mm. The compliance with the RTOG 0631 protocol, conformity index (CI), dose
      gradient index (DGI), and number of monitor units (MUs) were compared. The
      average V16Gy of the targets was 91.8 +/- 1.2%, 92.2 +/- 2.1%, and 91.7 +/- 2.3%
      for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively (p = 0.78). Accordingly, the
      average CI was 1.45 +/- 0.4, 1.47 +/- 0.29, and 1.47 +/- 0.31 (p = 0.98),
      respectively. The average DGI was 0.22 +/- 0.04, 0.20 +/- 0.06, and 0.22 +/-
      0.05, respectively (p = 0.77). The average maximum dose to the spinal cord was
      12.45 +/- 1.0 Gy, 12.80 +/- 1.0 Gy, and 12.48 +/- 1.1 (p = 0.62) and V10% of the
      spinal cord was 3.6 +/- 2.1%, 5.6 +/- 2.8%, and 5.5 +/- 3.0% (p = 0.11) for 2.5
      mm, 4-mm, and 5-mm leaf widths, respectively. Accordingly, the average number of
      MUs was 4341 +/- 500 MU, 5019 +/- 834 MU, and 4606 +/- 691 MU, respectively (p =
      0.053). The use of 2.5-mm, 4-mm, and 5-mm MLCs achieved similar VMAT plan quality
      as recommended by the RTOG 0631. The dosimetric parameters were also comparable
      for the 3 MLCs. In general, any of these leaf widths can be used for spine SBRT
      using VMAT.

PMID- 28457724
TI  - Effects of pre-overwintering conditions on eupyrene and apyrene spermatogenesis
      after overwintering in Polygonia c-aureum (Lepidoptera: Nymphalidae).
AB  - Sperm polymorphism is widely known in invertebrates. In insects, Lepidoptera has
      two types of sperm: nucleated eupyrene (fertile) sperm and anucleated apyrene
      (unfertile) sperm. These sperm types are produced during post-embryogenesis, and
      eupyrene spermatogenesis precedes apyrene spermatogenesis. During overwintering,
      spermatogenesis stops and a portion of undifferentiated-stage spermatocytes
      degenerate. After overwintering, spermatogenesis restarts with unaffected
      spermatogonia. However, how new spermatozoa arise in the adult testes after
      overwintering is not known in Lepidoptera. In this study, we investigated the
      spermatogenesis events in the nymphalid butterfly Polygonia c-aureum after
      overwintering under various environmental conditions. Our results indicate that
      both eupyrene and apyrene spermatogenesis restart at any stopping stage and sperm
      of these types are regenerated in no particular order after adult insect
      overwintering. This suggests that the spermatogenesis occurring after
      overwintering proceeds without embryogenetic restrictions related to the
      developmental sequence.

PMID- 28457725
TI  - Non-surgical treatments for hidradenitis suppurativa: A systematic review.
AB  - INTRODUCTION: The management of hidradenitis suppurativa is multidisciplinary,
      involving general measures, medical treatment and surgery. Non-surgical
      treatments, often first-line procedures, mainly concern forms of low-to-moderate
      severity or, conversely, very severe forms in non-operable patients or those
      refusing surgery. While many treatments have been attempted, few randomized
      controlled trials have been conducted, so the choice of treatments is most often
      based on the personal experience of the clinicians. The objective of this
      systematic review is to propose a synthetic analysis of the currently available
      non-surgical procedures. METHODS: This systematic review of the literature was
      conducted in accordance with the PRISMA criteria. We searched for articles in the
      Medline(r), PubMed Central, Embase and Cochrane databases published between
      January 2005 and September 2015. RESULTS: Sixty-four articles were included. They
      generally had a low level of evidence; indeed, the majority of them were
      retrospective observational studies. They involved biotherapy (44%), dynamic
      phototherapy (16%), antibiotics (11%), Laser (8%), retinoids (6%) and
      immunosuppressive therapies, anti-inflammatory drugs, zinc, metformin,
      gammaglobulins and fumarates. CONCLUSIONS: None of the non-surgical treatments
      can treat all stages of the disease and offer long-term remission. Antibiotics
      and biotherapy seem to have real effectiveness but their effect remains
      suspensive and the disease is almost certain to reappear once they are stopped.
      As regards antibiotics, no association has shown their superiority in a study
      with a high level of evidence. And while some biotherapies seem quite effective,
      due to their side effects they should be reserved for moderate-to-severe,
      resistant or inoperable forms of the disease. Randomized controlled studies are
      needed before valid conclusions can be drawn. In the resistant or disabling
      forms, it is consequently advisable to orientate to the greatest possible extent
      towards radical surgery, which is the only treatment allowing hope for cure.

PMID- 28457726
TI  - Cell-assisted lipotransfer: Current concepts.
AB  - Autologous fat transfer, or lipofilling, is a common technique used for soft
      tissue reconstruction. It has been used for many years, but the technique is
      associated with a significant graft resorption rate (20% to 80%). To improve the
      fat graft survival rate, several methods have been tested, and one has appeared
      more promising: cell-assisted lipotransfer (CAL). In the CAL method, fat is
      enriched with adipose-derived stromal cells (ASC), contained in the stromal
      vascular fraction (SVF) obtained after enzymatic digestion of fat or after cell
      culture to improve the fat survival rate. In this concise review, we present the
      clinical indications, and the technical principles of CAL, as well as a
      presentation of ASC. To conclude, we present the main results (efficacy,
      complications and safety) obtained from different studies of this technique.

PMID- 28457727
TI  - [Orbitofrontal bone reconstruction with cutting guides].
AB  - INTRODUCTION: Reconstruction of craniofacial defects due to traumatic injuries is
      a challenge for a reconstructive surgeon, given the functional impact, the
      aesthetic impact and the geometric complexity of the craniofacial skeleton. The
      use of cutting and repositioning guides enables a new approach from the
      craniofacial reconstruction with bone grafts on measure. We are presented to
      illustrate this technique the case of a patient. OBSERVATION: The patient was 50
      years old, he presented a traumatic facial sequelar: a left frontal craniofacial
      deformation, an enlarged left orbit with enophthalmos and valgus left zygoma. The
      patient had a permanent diplopia, an important aesthetic and social gene impeding
      daily life. Surgical planning was performed for optimal care. We performed a
      cranioplasty frontotemporal by bone parietal duplication, osteotomy of zygoma and
      intra-orbital bone graft customized using cutting guides. The bone pieces were
      positioned with the repositioning books. DISCUSSION: This presentation
      illustrates a novel application of cutting guides. This technique has the
      advantage of using customized autologous bone. This is the gold standard, it
      requires surgical experience.

PMID- 28457728
TI  - SOX-11 detection in decalcified bone marrow tissue in mantle cell lymphoma
      patients, methodological issue on reproducibility and validity.

PMID- 28457729
TI  - Genetic profile of ductal adenocarcinoma of the prostate.
AB  - Despite being discovered almost 50 years ago, little is known regarding the
      genetic profile of ductal adenocarcinoma of the prostate (DAC). In recent years,
      progress has been made in the understanding of the genetics of acinar
      adenocarcinomas, and at least 7 genetically different subtypes have been
      identified. DAC is known to present at an advanced stage with a high rate of
      extraprostatic extension and seminal vesicle invasion, and a decreased interval
      to biochemical recurrence and the development of metastatic disease when compared
      with acinar adenocarcinoma. Our aim was to investigate the genetic profile of DAC
      to determine whether there is a genomic rationale for the aggressive behavior
      associated with this tumor type. Frozen tissue from 11 cases of DAC with paired
      benign tissue was analyzed. After DNA extraction, copy-number alteration analysis
      was performed, as well as identification of mutations and indels. We compared the
      fraction of the DAC genome with copy-number alteration to previous results from
      74 primary acinar adenocarcinomas of the prostate. The alteration rate in DAC was
      comparable to that of acinar adenocarcinoma of high Gleason score. DAC harbored
      somatic changes seen in advanced and/or metastatic castration-resistant acinar
      adenocarcinoma, which likely accounts for its aggressive biological behavior.

PMID- 28457730
TI  - Comparison of estrogen receptor, progesterone receptor and HER2 results in
      concurrent ipsilateral samples with invasive breast carcinoma: a retrospective
      study of 246 biopsies from 119 patients.
AB  - There is no consensus regarding biomarker testing on the ipsilateral breast
      carcinomas present in separate biopsies, irrespective of whether the biopsies are
      performed concurrently or consecutively. We aimed to investigate estrogen
      receptor (ER), progesterone receptor (PR) and HER2 concordance in ipsilateral
      concurrent biopsies with invasive breast tumors. Consecutive ipsilateral
      concurrent biopsies with invasive breast tumors were identified retrospectively.
      Biomarker results, histologic grade and histologic subtype among the tumors in
      concurrent samples were compared. ER, PR, and HER2 expression was different in 3
      (2.5%), 11 (9.2%) and 7 (5.9%) cases, respectively. All ER-discordant cases were
      sets of ER-negative (ER-) and weak-low ER-positive (ER+), ductal subtype and
      histologic grade 2 or 3 tumors. All PR-discordant cases were ER+, and comprised
      of histologic grades 1 to 3 ductal as well as lobular tumors. All HER2 discordant
      cases were histologic grade 2 to 3 ductal tumors. Biomarker discordance was
      independent of grade and subtype discordance. We found very low biomarker
      discordance among tumors in concurrent samples from ipsilateral breast. Our
      results suggest that ER and HER2 discordance in concurrent samples is
      predictable. ER discordance is present only in a setting of low ER+ tumors. Low
      grade ductal and/or lobular tumors are ER and HER2 concordant. HER2 discordance
      is noted in grade 2 to 3 ductal tumors only. Histologic subtype and grade may
      guide extent of biomarker testing in concurrent ipsilateral breast biopsies.

PMID- 28457731
TI  - Expression pattern of cancer-associated fibroblast and its clinical relevance in
      intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and lack of
      effective treatment, characterized by dense desmoplastic stroma rich in cancer
      associated fibroblasts (CAFs), which have been indicated to facilitate tumor
      progression in several types of human cancer. However, the clinical relevance of
      CAFs in ICC has not been fully characterized. Here, we evaluated the histological
      phenotype of CAFs and immunohistochemical expressions of alpha-SMA, FSP-1, and
      PDGFRbeta in 71 ICC cases, and found that immature CAF phenotype was
      significantly associated with lymph node metastasis (P=.045), advanced TNM stage
      (P=.025) and poor 5-year overall survival (OS) (38.5% versus 78.6%, P=.015). In
      addition, alpha-SMA, FSP-1, and PDGFRbeta were positively expressed in stromal
      fibroblasts in 63.4% (45/71), 84.5% (60/71), and 78.9% (56/71) of patients,
      respectively. Positive expression of alpha-SMA was correlated with poor
      differentiation (P=.032); FSP-1 expression in stromal fibroblasts was linked with
      lymph node metastasis (P=.022) and immature phenotype (P=.048). What's more,
      positive expression of FSP-1 in cancer cells was observed in 22.5% (16/71) of
      cases and was correlated with worse 5-year OS (36.4% versus 76.7%, P=.014).
      Importantly, in multivariate analysis, histological CAF phenotype was an
      independent prognostic factor for OS in ICC. Our findings demonstrated
      histological categorization of CAFs was a useful predictor for prognosis,
      providing new evidence that CAFs play a crucial role in tumor progression and can
      serve as potential therapeutic targets in ICC.

PMID- 28457732
TI  - Causal inference between bioavailability of heavy metals and environmental
      factors in a large-scale region.
AB  - The causation between bioavailability of heavy metals and environmental factors
      are generally obtained from field experiments at local scales at present, and
      lack sufficient evidence from large scales. However, inferring causation between
      bioavailability of heavy metals and environmental factors across large-scale
      regions is challenging. Because the conventional correlation-based approaches
      used for causation assessments across large-scale regions, at the expense of
      actual causation, can result in spurious insights. In this study, a general
      approach framework, Intervention calculus when the directed acyclic graph (DAG)
      is absent (IDA) combined with the backdoor criterion (BC), was introduced to
      identify causation between the bioavailability of heavy metals and the potential
      environmental factors across large-scale regions. We take the Pearl River Delta
      (PRD) in China as a case study. The causal structures and effects were identified
      based on the concentrations of heavy metals (Zn, As, Cu, Hg, Pb, Cr, Ni and Cd)
      in soil (0-20 cm depth) and vegetable (lettuce) and 40 environmental factors
      (soil properties, extractable heavy metals and weathering indices) in 94 samples
      across the PRD. Results show that the bioavailability of heavy metals (Cd, Zn,
      Cr, Ni and As) was causally influenced by soil properties and soil weathering
      factors, whereas no causal factor impacted the bioavailability of Cu, Hg and Pb.
      No latent factor was found between the bioavailability of heavy metals and
      environmental factors. The causation between the bioavailability of heavy metals
      and environmental factors at field experiments is consistent with that on a large
      scale. The IDA combined with the BC provides a powerful tool to identify
      causation between the bioavailability of heavy metals and environmental factors
      across large-scale regions. Causal inference in a large system with the dynamic
      changes has great implications for system-based risk management.

PMID- 28457733
TI  - Characterisation and source identification of the total airborne particulate
      matter collected in an urban area of Aracaju, Northeast, Brazil.
AB  - In this work, studies using samples collected in an urban area of Aracaju city,
      Sergipe State, Northeast, Brazil revealed that soil dust in suspension was the
      main source of total airborne particulate matter (TAPM), followed by vehicular
      pollution. The concentration profiles for Cu, Fe, Mn, Ni, V and Ti were
      established for the collected TAPM samples. The concentrations of SO2 and smoke
      were also measured all along the 42 sampling days. Through multivariate data
      analysis of the results a correlation between Fe, Mn, Ni and Ti in the mineral
      composition of the particles was established, indicating soil dust in suspension
      as the main source of TAPM. The concentrations of Cu and smoke were found to be
      related to vehicular traffic, and the second largest source of TAPM. Enrichment
      factors (EF) were calculated for the studied elements, and only Cu was found to
      be enriched. The concentrations of the elements in TAPM were evaluated using the
      geoaccumulation index (Igeo), and Fe, Mn, Ni, V and Ti were found to derive from
      natural sources, in TAPM. However, approximately 55% of the samples did not
      presented Cu contamination (Igeo<=0), and the remaining 45% presented Cu
      concentrations levels that indicated between low to moderate (0<Igeo<=1) and
      moderate to heavy contamination (2<Igeo<=3) in the urban area of Aracaju city,
      Sergipe State, Northeast, Brazil.

PMID- 28457734
TI  - Adsorptive removal of pharmaceutical antibiotics from aqueous solution by porous
      covalent triazine frameworks.
AB  - The exposures of pharmaceutical antibiotics in water solution caused potential
      risks for ecological environment and human health. In the present study, porous
      covalent triazine frameworks (CTFs) were synthesized and the adsorption behavior
      of sulfamethoxazole (SMX) and tylosin (TL) was investigated. The CTFs were
      characterized by X-ray diffraction, transform infrared and N2
      adsorption/desorption. Sulfamethoxazole displayed much stronger adsorption than
      tylosin on microporous CTF-1 adsorbent due to the pore-filling effect. While the
      adsorption of bulky tylosin on microporous CTF-1 was suppressed because of the
      size exclusion effect. Additionally, the porous CTFDCBP showed stronger
      adsorption affinity and faster adsorption kinetics than other porous adsorbents,
      which was attributed to wide pore size distribution and open pore structure.
      Findings in this study highlight the potential of using porous CTFs as a
      potential adsorbent to eliminate antibiotics from water, especially for selective
      adsorption of bulky molecular pollutant.

PMID- 28457735
TI  - Association between ambient fine particulate matter and preterm birth or term low
      birth weight: An updated systematic review and meta-analysis.
AB  - An increasing number of studies have been conducted to determine a possible
      linkage between maternal exposure to ambient fine particulate matter and effects
      on the developing human fetus that can lead to adverse birth outcomes, but, the
      present results are not consistent. A total of 23 studies published before July
      2016 were collected and analyzed and the mean value of reported exposure to fine
      particulate matter (PM2.5) ranged from 1.82 to 22.11 We found a significantly
      increased risk of preterm birth with interquartile range increase in PM2.5
      exposure throughout pregnancy (odds ratio (OR) = 1.03; 95% conditional
      independence (CI): 1.01-1.05). The pooled OR for the association between PM2.5
      exposure, per interquartile range increment, and term low birth weight throughout
      pregnancy was 1.03 (95% CI: 1.02-1.03). The pooled ORs for the association
      between PM2.5 exposure per 10 increment, and term low birth weight and preterm
      birth were 1.05 (95% CI: 0.98-1.12) and 1.02 (95% CI: 0.93-1.12), respectively
      throughout pregnancy. There is a significant heterogeneity in most meta-analyses,
      except for pooled OR per interquartile range increase for term low birth weight
      throughout pregnancy. We here show that maternal exposure to fine particulate air
      pollution increases the risk of preterm birth and term low birth weight. However,
      the effect of exposure time needs to be further explored. In the future,
      prospective cohort studies and personal exposure measurements needs to be more
      widely utilized to better characterize the relationship between ambient fine
      particulate exposure and adverse birth outcomes.

PMID- 28457737
TI  - Atrial Fibrillation and End Stage Renal Failure in Patients Receiving Dialysis:
      Balancing the Risks and Benefits of Stroke Prevention.

PMID- 28457736
TI  - Cost of Congenital Heart Disease Hospitalizations in Canada: A Population-Based
      Study.
AB  - BACKGROUND: The prevalence of congenital heart disease (CHD) is rising, and late
      complications are common. The impact of these factors on health-care costs is not
      well understood. We sought to describe inpatient CHD costs in Canada. METHODS: We
      conducted an observational retrospective cohort study. The Canadian Institute for
      Health Information (CIHI) Discharge Abstract Database was used for all Canadian
      provinces, except Quebec, between April 2004 and March 2014. We included
      hospitalizations with a main diagnosis of CHD (International Classification of
      Diseases, 10th revision, codes Q20.0-26.9) and hospitalizations having CHD as a
      secondary diagnosis if the main diagnosis was a comorbid condition related to
      CHD. CIHI patient cost estimates were used to provide dollar values. Costs were
      inflated to 2016 Canadian dollars. RESULTS: Among 59,917 hospitalizations, annual
      CHD costs increased by 21.6% from CAD$99.7 million (95% confidence interval [CI],
      $89.4-$110.1 million) in 2004 to $121.2 million (95% CI, $112.8-$129.6 million)
      in 2013 (P < 0.001). Costs were higher for children compared with adults.
      However, the cost increase was greater in adults (4.5%/y; P < 0.001) than in
      children (0.7%/y; P = 0.006). Adults accounted for 38.2% of costs in 2004 vs
      45.8% in 2013 (P = 0.002). Costs increased most among adults with complex CHD
      (7.2%/y; P = 0.001). Adult men accounted for greater increases in costs relative
      to women (P < 0.001). Length of stay was unchanged over time. CONCLUSIONS:
      Inpatient CHD costs are increasing independent of inflation, particularly among
      adults with complex lesions. Although children still account for greater
      inpatient CHD costs, a larger increase was observed among adults. These data are
      important in allocating inpatient resources for adults with CHD.

PMID- 28457738
TI  - Acromegalic Cardiomyopathy With Malignant Arrhythmogenic Pattern Successfully
      Treated With Mechanical Circulatory Support and Heart Transplantation.
AB  - Cardiovascular involvement is common in acromegaly and can lead to development of
      acromegalic cardiomyopathy, characterized by concentric biventricular hypertrophy
      with a progressive impairment of diastolic and systolic function. The onset of
      heart failure and arrhythmias are related to poor prognosis. We report on a case
      of a 48-year-old man with acromegalic cardiomyopathy caused by pituitary adenoma.
      Despite the successful trans-sphenoidal resection of the tumour, the patient was
      rehospitalized for ventricular arrhythmic storms that led to cardiogenic shock,
      which required mechanical hemodynamic support with intra-aortic balloon pump,
      venoarterial extracorporeal membrane oxygenation, and urgent heart
      transplantation.

PMID- 28457739
TI  - Mesenchymal stromal cells from umbilical cord Wharton's jelly trigger
      oligodendroglial differentiation in neural progenitor cells through cell-to-cell
      contact.
AB  - BACKGROUND AIMS: Wharton's jelly mesenchymal stromal cells (WJ-MSCs) might be
      ideal candidates to treat perinatal brain damage. Their secretome has been shown
      to have beneficial effects on neuroregeneration, in part through interaction with
      neural progenitor cells (NPCs). However, it remains unclear whether cell-to-cell
      contact decisively contributes to this positive effect. The objective of this
      study was to elucidate the mechanism through which differentiation in NPCs is
      triggered after exposure to WJ-MSCs. Furthermore, given that WJ-MSCs can be
      derived from term (tWJ-MSCs) or preterm (ptWJ-MSCs) deliveries and that WJ-MSCs
      might be used for transplantations independent of gestational age, the influence
      of tWJ-MSCs versus ptWJ-MSCs on the differentiation capacities of NPCs was
      studied. METHODS: The effect of tWJ-MSCs and ptWJ-MSCs on the expression of
      neuroglial markers in NPCs was assessed in co-culture (CC), conditioned medium
      (CM) or transwell CC experiments by immunocytochemistry, real-time polymerase
      chain reaction and Western blot. Additionally, mass spectrometry was used to
      study their secretomes. RESULTS: NPCs showed an increased expression of glial
      markers after CC with WJ-MSCs or exposure to WJ-MSC-CMs. CC had a more prominent
      effect on the expression of glial markers compared with CM or transwell CCs. tWJ
      MSCs more strongly induced the expression of mature oligodendroglial markers
      compared with ptWJ-MSCs. A possible role in enhancing this maturation could be
      attributed to the laminin alpha2-subunit. CONCLUSIONS: Cell-to-cell contact
      between WJ-MSCs and NPCs induces oligodendrogenesis on NPCs, whereas trophic
      factor secretion is sufficient to promote astrogenesis. Thus, transplanting WJ
      MSCs may promote endogenous neuroregeneration in perinatal brain damage.

PMID- 28457740
TI  - Regulatory perspective on in vitro potency assays for human mesenchymal stromal
      cells used in immunotherapy.
AB  - Mesenchymal stromal cells (MSCs) are multipotent cells derived from various
      tissues that can differentiate into several cell types. MSCs are able to modulate
      the response of immune cells of the innate and adaptive immune system. Because of
      these multimodal properties, the potential use of MSCs for immunotherapies is
      currently explored in various clinical indications. Due to the diversity of
      potential MSC medicinal products at the level of cell source, manufacturing
      process and indication, distinct functionality tests may be needed to ensure the
      quality for each of the different products. In this review, we focus on in vitro
      potency assays proposed for characterization and release of different MSC
      medicinal products. We discuss the most used functional assays, as presented in
      scientific advices and literature, highlighting specific advantages and
      limitations of the various assays. Currently, the most proposed and accepted
      potency assay for release is based on in vitro inhibition of T cell proliferation
      or other functionalities. However, for some products, assays based on other MSC
      or responder cell properties may be more appropriate. In all cases, the
      biological relevance of the proposed assay for the intended clinical activity
      should be substantiated with appropriate product-specific (non-)clinical data. In
      case practical considerations prevent the use of the ideal potency assay at
      release, use of a surrogate marker or test could be considered if correlation
      with functionality has been demonstrated. Nevertheless, as the field of MSC
      immunology is evolving, improvements can be expected in relevant assays and
      consequently in guidance related to potency testing.

PMID- 28457741
TI  - Commissioning of applicator-guided stereotactic body radiation therapy boost with
      high-dose-rate brachytherapy for advanced cervical cancer using radiochromic film
      dosimetry.
AB  - PURPOSE: To describe an EBT3 GAFCHROMIC film-based dosimetry method to be used in
      commissioning of a combined HDR brachytherapy (HDRB) and stereotactic body
      radiation therapy (SBRT) boost for treatment of advanced cervical cancer
      involving extensive residual disease after external beam treatment. METHODS AND
      MATERIALS: A cube phantom was designed to firmly fit an intrauterine tandem
      applicator and EBT3 radiochromic film pieces. A high-risk clinical target volume
      (CTVHR, Total) was contoured with an extended arm at one side. The HDRB treatment
      was planned to cover the proximal CTVHR, Total with 7 Gy and the distal volume,
      referred to as CTVHR, Distal, was planned by SBRT for dose augmentation. After
      HDRB treatment delivery, SBRT treatment was delivered within 1 hour by image
      guidance using the applicator geometry. Intentional 1D and 2D misalignments were
      introduced to evaluate the effect on target volumes. In addition, effect of film
      reirradiation at different time gaps and dose levels was evaluated. RESULTS: Film
      dosimetric accuracy, with up to 2 hours gap between irradiations, was shown to be
      unaffected. A 2%/2 mm gamma analysis between measured and planned doses showed
      agreement of >99%. Misalignments of more than 2 mm between applicator and SBRT
      isocenter resulted in suboptimal dose-volume histogram affecting mostly D98% and
      D90% of CTVHR, Distal. CONCLUSIONS: Visualizing how target dose-volume metrics
      are affected by minor misalignments between SBRT and HDRB dose gradients, in
      light of achievable phantom-based experimental quality assurance level,
      encourages the clinical applicability of this technique. Radiochromic film was
      shown to be a valuable tool to commission procedures combining two different
      treatment planning systems and modalities with varying dose rates and energy
      ranges.

PMID- 28457742
TI  - From individual to herd protection with pneumococcal vaccines: the contribution
      of the Cuban pneumococcal conjugate vaccine implementation strategy.
AB  - A new pneumococcal conjugate vaccine is currently undergoing advanced clinical
      evaluation prior to its planned introduction in Cuba. The implementation of the
      pneumococcal vaccination strategy has been designed with consideration of the
      need to maximize both its direct and indirect effects. A novel approach is
      suggested, which addresses preschool children as the first-line target group to
      generate herd immunity in infants and to have an impact on transmission at the
      community level. The clinical evaluation pipeline is described herein, including
      evaluations of effectiveness, cost-effectiveness, and impact. The scientific
      contribution of the Cuban strategy could support a paradigm shift from individual
      protection to a population effect based on a rigorous body of scientific
      evidence.

PMID- 28457743
TI  - The information needs of patients receiving procedural sedation in a hospital
      emergency department.
AB  - This research investigated the information needs of patients receiving ED
      procedural sedation to determine the best format to consistently deliver key
      information in a way acceptable to all involved. Of particular interest was the
      question concerning patients' need for receiving written information. A
      descriptive exploratory study gathered qualitative data through face-to-face
      interviews and focus groups involving patients, nurses and medical staff.
      Individual interviews were conducted with eight adult patients following
      procedural sedation. They identified very few gaps in terms of specific
      information they needed pertaining to procedural sedation and rejected the need
      for receiving information in a written format. Their information needs related to
      a central concern for safety and trust. Focus groups, reflecting on the findings
      from patients, were conducted with five ED nurses and four emergency medicine
      consultants/registrars who regularly provided procedural sedation. Themes that
      emerged from the analysis of data from all three groups identified the issues
      concerning patient information needs as being: competence and efficiency of
      staff; explanations of procedures and progress; support person presence; and
      medico-legal issues. The research confirms that the quality of the patient's ED
      experience, specifically related to procedural sedation, is enhanced by ED staff,
      especially nurses, providing them with ongoing and repeated verbal information
      relevant to their circumstances.

PMID- 28457744
TI  - Piwi Is Required during Drosophila Embryogenesis to License Dual-Strand piRNA
      Clusters for Transposon Repression in Adult Ovaries.
AB  - Most piRNAs in the Drosophila female germline are transcribed from
      heterochromatic regions called dual-strand piRNA clusters. Histone 3 lysine 9
      trimethylation (H3K9me3) is required for licensing piRNA production by these
      clusters. However, it is unclear when and how they acquire this permissive
      heterochromatic state. Here, we show that transient Piwi depletion in Drosophila
      embryos results in H3K9me3 decrease at piRNA clusters in ovaries. This is
      accompanied by impaired biogenesis of ovarian piRNAs, accumulation of
      transposable element transcripts, and female sterility. Conversely, Piwi
      depletion at later developmental stages does not disturb piRNA cluster licensing.
      These results indicate that the identity of piRNA clusters is epigenetically
      acquired in a Piwi-dependent manner during embryonic development, which is
      reminiscent of the widespread genome reprogramming occurring during early
      mammalian zygotic development.

PMID- 28457745
TI  - Sensory hypersensitivity predicts enhanced attention capture by faces in the
      early development of ASD.
AB  - Sensory sensitivity is prevalent among young children with ASD, but its relation
      to social communication impairment is unclear. Recently, increased sensory
      hypersensitivity has been linked to greater activity of the neural salience
      network (Green et al., 2016). Increased neural sensitivity to stimuli, especially
      social stimuli, could provide greater opportunity for social learning and
      improved outcomes. Consistent with this framework, in Experiment 1 we found that
      parent report of greater sensory hypersensitivity at 2 years in toddlers with ASD
      (N=27) was predictive of increased neural responsiveness to social stimuli
      (larger amplitude event-related potential/ERP responses to faces at P1, P400 and
      Nc) at 4 years, and this in turn was related to parent report of increased social
      approach at 4 years. In Experiment 2, parent report of increased perceptual
      sensitivity at 6 months in infants at low and high familial risk for ASD (N=35)
      predicted larger ERP P1 amplitude to faces at 18 months. Increased sensory
      hypersensitivity in early development thus predicted greater attention capture by
      faces in later development, and this related to more optimal social behavioral
      development. Sensory hypersensitivity may index a child's ability to benefit from
      supportive environments during development. Early sensory symptoms may not always
      be developmentally problematic for individuals with ASD.

PMID- 28457746
TI  - Comparing the Palliative Care Needs of Those With Cancer to Those With Common Non
      Cancer Serious Illness.
AB  - BACKGROUND: Historically, palliative care has been focused on those with cancer.
      Although these ties persist, palliative care is rapidly integrating into the care
      of patients with common, non-cancer serious illnesses. Despite this, the bulk of
      literature informing palliative care practices stems from the care of cancer
      patients. OBJECTIVES: We compared functionality, advanced care planning, hospital
      admissions, prognosis, quality of life, pain, dyspnea, fatigue, and depression
      between patients with cancer and three non-cancer diagnoses-end-stage renal
      disease (ESRD), heart failure (HF), and chronic obstructive pulmonary disease
      (COPD). METHODS: We conducted a cross-sectional, retrospective analysis of the
      characteristics and symptoms of patient's with ESRD, HF, COPD, and cancer at time
      of first specialty palliative care referral. Using a web-based point of care
      quality assessment and reporting tool, Quality Data and Collection Tool
      Palliative care, this analysis evaluated all eligible patients who received a
      palliative care consultation between October 1, 2012 and November 25, 2014. Data
      were obtained from 13 participating sites. The primary outcome for the study was
      functionality using the palliative performance scale. Hospital admission in the
      last 30 days, prognosis, patient's understanding of prognosis, advanced care
      planning including code status and appointed decision maker, pain, fatigue,
      depression, and dyspnea were also evaluated as secondary outcomes. We tested for
      an association between our outcomes with disease type (cancer vs. non-cancer)
      fitting multivariable logistic regression models. RESULTS: We found that the
      patients with primary diagnoses other than cancer were less functional at time of
      referral (odds ratio: 1.6; 95% CI: 1.1, 2.3; P < 0.05). CONCLUSION: Patients with
      COPD, ESRD, and HF were less functional and more likely to be hospitalized at
      time of referral to palliative care than cancer patients. These findings may be
      reflective of the slower and more varied trajectory of non-cancer serious
      illness. One aim of palliative care for those with non-cancer severe illness
      should be directed toward improving and assisting with functionality and
      decreasing frequency of hospital admissions. These interventions could take place
      in the palliative care office, but could also be integrated into hospital
      discharge plans.

PMID- 28457747
TI  - Food Insecurity and Mental Health Status: A Global Analysis of 149 Countries.
AB  - INTRODUCTION: This study sought to determine the association of individual-level
      food insecurity (FI) with mental health status across all global regions.
      METHODS: Cross-sectional data were analyzed in 2016 from the 2014 Gallup World
      Poll, a series of globally implemented, nationally representative surveys. FI was
      assessed using the Food Insecurity Experience Scale Survey Module for
      Individuals, an eight-question psychometric scale reporting individuals'
      experiences of FI. Individual-level composite indices of mental health, the
      Negative Experience Index and Positive Experience Index (0-100 scale), were
      calculated based on responses to five questions of respondents' recent negative
      and positive experiences, respectively, associated with depression and mental
      distress. RESULTS: The prevalence of any FI ranged from 18.3% in East Asia to
      76.1% in Sub-Saharan Africa. In global analyses (149 countries) using adjusted
      multiple regression analyses, FI was associated in a dose-response fashion with
      poorer scores on the mental health indices (coefficient [95% CI]: Negative
      Experience Index: mild FI, 10.4 [9.5, 11.2]; moderate FI, 17.7 [16.4, 19.0];
      severe FI, 24.5 [22.7, 26.3]; Positive Experience Index: mild FI, -8.3 [-9.3, 
      7.4]; moderate FI, -12.6 [-13.8, -11.3]; severe FI, -16.2 [-17.9, -14.5]). Within
      region analyses (11 regions) consistently demonstrated the same trends.
      CONCLUSIONS: FI is associated with poorer mental health and specific psychosocial
      stressors across global regions independent of SES. The numerous pathways via
      which FI may contribute to common mental disorders, and the broad social
      implications of FI linked to cultural norms and self-efficacy, may contribute to
      the cross-cultural consistency of the findings.

PMID- 28457748
TI  - Gli1+ Mesenchymal Stromal Cells Are a Key Driver of Bone Marrow Fibrosis and an
      Important Cellular Therapeutic Target.
AB  - Bone marrow fibrosis (BMF) develops in various hematological and non
      hematological conditions and is a central pathological feature of myelofibrosis.
      Effective cell-targeted therapeutics are needed, but the cellular origin of BMF
      remains elusive. Here, we show using genetic fate tracing in two murine models of
      BMF that Gli1+ mesenchymal stromal cells (MSCs) are recruited from the endosteal
      and perivascular niche to become fibrosis-driving myofibroblasts in the bone
      marrow. Genetic ablation of Gli1+ cells abolished BMF and rescued bone marrow
      failure. Pharmacological targeting of Gli proteins with GANT61 inhibited Gli1+
      cell expansion and myofibroblast differentiation and attenuated fibrosis
      severity. The same pathway is also active in human BMF, and Gli1 expression in
      BMF significantly correlates with the severity of the disease. In addition,
      GANT61 treatment reduced the myofibroblastic phenotype of human MSCs isolated
      from patients with BMF, suggesting that targeting of Gli proteins could be a
      relevant therapeutic strategy.

PMID- 28457749
TI  - An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice.
AB  - Tissue homeostasis requires the production of newly differentiated cells from
      resident adult stem cells. Central to this process is the expansion of
      undifferentiated intermediates known as transit-amplifying (TA) cells, but how
      stem cells are triggered to enter this proliferative TA state remains an
      important open question. Using the continuously growing mouse incisor as a model
      of stem cell-based tissue renewal, we found that the transcriptional cofactors
      YAP and TAZ are required both to maintain TA cell proliferation and to inhibit
      differentiation. Specifically, we identified a pathway involving activation of
      integrin alpha3 in TA cells that signals through an LATS-independent
      FAK/CDC42/PP1A cascade to control YAP-S397 phosphorylation and nuclear
      localization. This leads to Rheb expression and potentiates mTOR signaling to
      drive the proliferation of TA cells. These findings thus reveal a YAP/TAZ
      signaling mechanism that coordinates stem cell expansion and differentiation
      during organ renewal.

PMID- 28457750
TI  - Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal
      Niche Interactions.
AB  - Human fetal germ cells (FGCs) are precursors to sperm and eggs and are crucial
      for maintenance of the species. However, the developmental trajectories and
      heterogeneity of human FGCs remain largely unknown. Here we performed single-cell
      RNA-seq analysis of over 2,000 FGCs and their gonadal niche cells in female and
      male human embryos spanning several developmental stages. We found that female
      FGCs undergo four distinct sequential phases characterized by mitosis, retinoic
      acid signaling, meiotic prophase, and oogenesis. Male FGCs develop through stages
      of migration, mitosis, and cell-cycle arrest. Individual embryos of both sexes
      simultaneously contain several subpopulations, highlighting the asynchronous and
      heterogeneous nature of FGC development. Moreover, we observed reciprocal
      signaling interactions between FGCs and their gonadal niche cells, including
      activation of the bone morphogenic protein (BMP) and Notch signaling pathways.
      Our work provides key insights into the crucial features of human FGCs during
      their highly ordered mitotic, meiotic, and gametogenetic processes in vivo.

PMID- 28457751
TI  - Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and
      predicting mortality with and without HIV: prospective TB cohort from the
      Thailand Big City TB Research Network.
AB  - OBJECTIVES: To evaluate the applicability and accuracy of the urine
      lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and
      HIV-negative patients with disseminated TB. METHODS: Frozen urine samples
      obtained at baseline from patients in the TB research cohort with proven culture
      positive TB were selected for blinded urine LAM testing. One hundred and nine
      patients were categorized into four groups: (1) HIV-positive patients with TB;
      (2) HIV-negative patients with disseminated TB; (3) HIV-negative
      immunocompromised patients with TB; and (4) patients with diseases other than TB.
      The sensitivity of urine LAM testing for culture-positive TB, specificity of
      urine LAM testing for patients without TB, positive predictive value (PPV), and
      negative predictive value (NPV) were assessed. RESULTS: The sensitivity of the
      urine LAM test in group 1 patients with a CD4 T-cell count of >100, <=100, and
      <=50 cells/mm3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV
      of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2
      and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A
      positive urine LAM test result was significantly associated with death.
      CONCLUSIONS: This promising diagnostic tool could increase the yield of TB
      diagnosis and may predict the mortality rate of TB infection, particularly in
      TB/HIV co-infected patients.

PMID- 28457752
TI  - Evaluation of the variability and safety of serum trough concentrations of
      vancomycin in patients admitted to the intensive care unit.
AB  - OBJECTIVE: To examine the variability and safety of serum trough concentrations
      of vancomycin in patients admitted to the intensive care unit (ICU) and to
      analyze the factors influencing the trough concentration. METHODS: Data were
      collected retrospectively from ICU patients receiving vancomycin treatment at a
      fixed dose of 2g/day due to unobtainable weight data, at Changzhou No. 2 People's
      Hospital, between 2012 and 2015. Vancomycin trough concentrations were compared
      between groups stratified by sex, age, and estimated glomerular filtration rate
      (eGFR). RESULTS: The vancomycin trough concentration varied significantly among
      ICU patients on a fixed dose of 2g/day. Only 16.9% of ICU patients met the
      concentration target of 15-20mg/l, while 25% of patients showed supratherapeutic
      concentrations. A higher proportion of female patients than male patients showed
      supratherapeutic concentrations (40.4% vs. 15.5%). The trough concentration was
      positively correlated with age (y=0.279x-2.085; R2=0.186) and negatively
      correlated with eGFR (y=-0.2x+33.776; R2=0.366). Vancomycin-related
      nephrotoxicity occurred at an incidence of 5.9%. CONCLUSIONS: These results
      suggest that the fixed-dose regimen is not appropriate for ICU patients in view
      of the low incidence of target trough concentrations and the high incidence of
      supratherapeutic concentrations. The dose should be individualized based on
      weight, age, and renal function to improve outcomes and patient safety.

PMID- 28457754
TI  - Investigation of the structural requirements of K-Ras(G12D) selective inhibitory
      peptide KRpep-2d using alanine scans and cysteine bridging.
AB  - A structure-activity relationship study of a K-Ras(G12D) selective inhibitory
      cyclic peptide, KRpep-2d was performed. Alanine scanning of KRpep-2d focusing on
      the cyclic moiety showed that Leu7, Ile9, and Asp12 are the key elements for K
      Ras(G12D) selective inhibition of KRpep-2d. The cysteine bridging was also
      examined to identify the stable analog of KRpep-2d under reductive conditions. As
      a result, the KRpep-2d analog (12) including mono-methylene bridging showed
      potent K-Ras(G12D) selective inhibition in both the presence and the absence of
      dithiothreitol. This means that mono-methylene bridging is an effective strategy
      to obtain a reduction-resistance analog of parent disulfide cyclic peptides.
      Peptide 12 inhibited proliferation of K-Ras(G12D)-driven cancer cells
      significantly. These results gave valuable information for further optimization
      of KRpep-2d to provide novel anti-cancer drug candidates targeting the K
      Ras(G12D) mutant.

PMID- 28457753
TI  - Expression of CD25 on leukemic stem cells in BCR-ABL1+ CML: Potential diagnostic
      value and functional implications.
AB  - Chronic myeloid leukemia (CML) is a stem cell-derived leukemia in which
      neoplastic cells exhibit the Philadelphia chromosome and the related oncoprotein
      BCR-ABL1. The disease is characterized by an accumulation of myeloid precursor
      cells in the peripheral blood and bone marrow (BM). A small fraction of
      neoplastic cells in the CML clone supposedly exhibits self-renewal and thus long
      term disease-propagating ability. However, so far, little is known about the
      phenotype, function, and target expression profiles of these leukemic stem cells
      (LSCs). Recent data suggest that CML LSCs aberrantly express the interleukin-2
      receptor alpha chain CD25. Whereas normal CD34+/CD38- BM stem cells display only
      low amounts of CD25 or lack CD25 altogether, CD34+/CD38- LSCs express CD25
      strongly in more than 90% of all patients with untreated CML. As a result, CD25
      can be used to identify and quantify CML LSCs. In addition, it has been shown
      that CD25 serves as a negative growth regulator of CML LSCs. Here, we review the
      value of CD25 as a novel marker and potential drug target in CML LSCs.

PMID- 28457755
TI  - Nucleobase azide-ethynylribose click chemistry contributes to stabilizing
      oligonucleotide duplexes and stem-loop structures.
AB  - The formation of 1,4-disubstituted 1,2,3-triazoles through copper-catalyzed azide
      alkyne cycloaddition (CuAAC) in oligonucleotides bearing 1-deoxy-1-ethynyl-beta-d
      ribofuranose (RE) can have a positive impact on the stability of oligonucleotide
      duplexes and stem-loop structures.

PMID- 28457756
TI  - Antitubulin effects of aminobenzothiophene-substituted triethylated chromones.
AB  - In the course of our continuing studies on the 2-(benzo[b]thiophene-3'-yl)-6,8,8
      triethyldesmosdumotin B (TEDB-TB) series, we designed and synthesized nine amino
      TEDB-TB derivatives to improve pharmaceutical properties, identify structure
      activity relationships, and discover novel antitubulin agents. Among all newly
      synthesized amino-TEDB-TBs, the 5'- and 6'-amino derivatives, 6 and 7, exhibited
      significant antiproliferative activity against five human tumor cell lines,
      including an MDR subline overexpressing P-gp. The IC50 values of 0.50-1.01uM were
      3-6 times better than those of previously reported hydroxy-TEDB-TBs. Compounds 6
      and 7 inhibited tubulin polymerization, induced both depolymerization of
      interphase microtubules and multiple spindle formations, and caused cell arrest
      at prometaphase. Among all compounds, compound 7 scored best pharmaceutically
      with LogP 2.11 and biologically with greater antiproliferative activity and
      induction of cell cycle arrest at prometaphase.

PMID- 28457757
TI  - Juvenile myasthenia gravis in Norway: Clinical characteristics, treatment, and
      long-term outcome in a nationwide population-based cohort.
AB  - BACKGROUND: This study aimed to characterize juvenile myasthenia gravis in a
      national population-based cohort in Norway, and to evaluate long-term outcome and
      potential differences correlated with prepubertal versus postpubertal disease
      onset. PATIENTS AND METHODS: Patients with onset of myasthenia gravis aged <=18
      years were identified through multiple strategies. Retrospective clinical data
      were collected by means of medical charts. All patients had an updated clinical
      examination. Cases were divided into prepubertal and postpubertal onset using age
      12 years as the cut off. RESULTS: In total, 75 patients were identified of whom
      63 were included in the study: 21 in the prepubertal and 42 in the postpubertal
      onset group. There was a female preponderance in both groups. In total, 59%
      presented with ocular symptoms, but the great majority of patients in both groups
      generalized during the two first years of the disease. Myasthenic crisis was more
      frequent in the prepubertal onset group. All patients were initially treated with
      pyridostigmine, 26 with steroids, and 17 with other immunosuppressive treatment.
      The postpubertal cases were more often treated with immunosuppressive therapy.
      Fifty patients (79%) underwent thymectomy. The general outcome was favourable:
      57% became asymptomatic and only four subjects failed to attain clinical
      improvement. One-third had at least one additional autoimmune disease.
      CONCLUSION: Despite frequent symptom generalization and a subgroup of prepubertal
      onset with severe disease, the long-term outcome was good, especially in the
      thymectomized prepubertal onset group. Polyautoimmunity occurred in both groups
      in one-third.

PMID- 28457758
TI  - Radiation Dose Reduction during Uterine Fibroid Embolization Using an Optimized
      Imaging Platform.
AB  - PURPOSE: To assess radiation dose reduction during uterine fibroid embolization
      (UFE) using an optimized angiographic processing and acquisition platform.
      MATERIALS AND METHODS: Radiation dose data for 70 women (mean age, 46 y; range,
      34-67 y) who underwent UFE were retrospectively analyzed. Twenty-one patients
      underwent UFE using the baseline fluoroscopic and angiographic image acquisition
      platform, and 49 underwent UFE after implementing an optimized imaging platform
      in otherwise identical angiography suites. Cumulative kerma-area product (CKAP),
      cumulative air kerma (CAK), total fluoroscopy time, and image exposure number
      were collected for each procedure. Image quality was assessed by 3 interventional
      radiologists blinded to the platform used for image acquisition and processing.
      RESULTS: Patients undergoing UFE using the new x-ray fluoroscopy platform had
      significantly lower CKAP and CAK indicators than patients for whom baseline
      settings were used. Mean CKAP decreased by 60% from 438.5 Gy . cm2 (range, 180.3
      1,081.1 Gy . cm2) to 175.2 Gy . cm2 (range, 47.1-757.0 Gy . cm2; P < .0001). Mean
      CAK decreased by 45% from 2,034.2 mGy (range, 699.3-5,056.0 mGy) to 1,109.8 mGy
      (range, 256.6-4,513.6 mGy; P = .001). No degradation of image quality was
      identified through qualitative evaluation. CONCLUSIONS: Significant reduction in
      patient radiation dose indicators can be achieved with use of an optimized image
      acquisition and processing platform.

PMID- 28457759
TI  - Modular Neck vs Nonmodular Femoral Stems in Total Hip Arthroplasty-Clinical
      Outcome, Metal Ion Levels, and Radiologic Findings.
AB  - BACKGROUND: Modular neck femoral stem (MNFS) for total hip arthroplasty (THA) was
      introduced to optimize the outcome, but created concerns about pain, elevated
      blood metal ion levels, and adverse reaction to metal debris such as pseudotumors
      (PTs), related to corrosion between femoral neck and stem. We compared these
      outcomes in patients with MNFS or nonmodular femoral stem (NFS) THA. METHODS:
      Thirty-three patients with unilateral MNFS THA were compared with 30 patients
      with unilateral NFS THA. Levels of pain, serum cobalt, serum chromium were
      determined. Magnetic resonance imaging was performed to describe PT and fatty
      atrophy of muscles. RESULTS: The MNFS and NFS group had a mean follow-up of 2.3
      and 3.1 years, respectively. Four and 13 patients in the MNFS and NFS group had
      pain, respectively (P = .005). The MNFS group had higher levels of serum cobalt
      (P < .0001) and chromium (P = .006). PTs were present in both the MNFS (n = 15)
      and NFS (n = 7) groups (P = .066). PTs were related to serum cobalt (P = .04) but
      not to pain or serum chromium. Fatty atrophy prevalence in the piriformis and
      gluteal muscles were higher in patients with MNFS (P = .009 and P = .032,
      respectively). CONCLUSION: More patients in the NFS group had pain. Serum cobalt
      and chromium levels were higher in the MNFS group. Prevalence of PTs was twice as
      high in the MNFS group, but the difference was insignificant.

PMID- 28457760
TI  - A Comparison Between Chinese and Caucasian 3-Dimensional Bony Morphometry in
      Presimulated and Postsimulated Osteotomy for Total Knee Arthroplasty.
AB  - BACKGROUND: The bone morphologies of intact knees were measured and compared
      between Chinese and Caucasian populations. However, to assess if distinct designs
      of implants are necessary for the Chinese population owing to different
      morphologies and sizes, the knee measurements after osteotomy performed in total
      knee arthroplasty were evaluated. METHODS: Thirty-seven Caucasian and 50 Chinese
      patients' knees were examined using computed tomography scans. Mimics were
      applied to reconstruct 3-dimensional bone models. Dimensions of the 3-dimensional
      knee models and simulated bone resections during total knee arthroplasty were
      measured using Geomagic Studio and Pro/ENGINEER. The morphologic measurements of
      the native and resected femur and tibia included the anteroposterior (AP) depth,
      mediolateral (ML) width, notch width, knee physical valgus angle, tibial slope
      angle, and the ML-to-AP ratio of the femur, tibia, and resected femur.
      Statistical analysis was performed using the independent samples t test and the
      Pearson correlation coefficient in SPSS for Windows. Values of P < .05 were
      considered significant. RESULTS: No measurements were significantly different
      between the Chinese and Caucasian knees. However, the Chinese female showed
      significant differences compared with the Chinese male on distal femoral
      measurements both presimulated and postsimulated osteotomy such as a smaller mean
      ML-to-AP ratio in presimulated (1.3 +/- 0.1) and postsimulated (1.3 +/- 0.1)
      osteotomy. CONCLUSION: The necessity of designing a full set of total knee
      components specifically for the Chinese population is still undetermined.
      However, we suggest designing femoral components specific for the Chinese females
      because of different postosteotomy distal femoral ML-to-AP ratio between the
      Chinese males and the Chinese females.

PMID- 28457761
TI  - Long-term survival of out-of-hospital cardiac arrest patients with malignancy.
AB  - BACKGROUND: The aim of this study was to investigate whether the 1-year survival
      rate of out-of-hospital cardiac arrest (OHCA) patients with malignancy was
      different from that of those without malignancy. METHODS: All adult OHCA patients
      were retrospectively analyzed in a single institution for 6years. The primary
      outcome was 1-year survival, and secondary outcomes were sustained return of
      spontaneous circulation (ROSC), survival to hospital admission, survival to
      discharge and discharge with a good neurological outcome (CPC 1 or 2). Kaplan
      Meier survival analysis and Cox proportional hazard regression analysis were
      performed to test the effect of malignancy. RESULTS: Among 341 OHCA patients, 59
      patients had malignancy (17.3%). Sustained ROSC, survival to admission, survival
      to discharge and discharge with a good CPC were not different between the two
      groups. The 1-year survival rate was lower in patients with malignancy (1.7% vs
      11.4%; P=0.026). Kaplan-Meier survival analysis revealed that patients with
      malignancy had a significantly lower 1-year survival rate when including all
      patients (n=341; P=0.028), patients with survival to admission (n=172, P=0.002),
      patients with discharge CPC 1 or 2 (n=18, P=0.010) and patients with discharge
      CPC 3 or 4 (n=57, P=0.008). Malignancy was an independent risk factor for 1-year
      mortality in the Cox proportional hazard regression analysis performed in
      patients with survival to admission and survival to discharge. CONCLUSIONS:
      Although survival to admission, survival to discharge and discharge with a good
      CPC rate were not different, the 1-year survival rate was significantly lower in
      OHCA patients with malignancy than in those without malignancy.

PMID- 28457762
TI  - Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal
      infection.
AB  - BACKGROUND: Esmolol is a highly selective beta 1 receptor blocker with various
      effects such as slowing heart rate, lowering blood pressure and reducing
      myocardial oxygen consumption. However, few studies have reported the use of beta
      blockers in sepsis with multiple organ dysfunctions. This study aimed to
      investigate the effects of esmolol on reducing apoptosis and inflammation in
      early sepsis rats with abdominal infection. METHODS: Rats were randomly divided
      into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic
      group with low, median and high dose Esmolol (L group, M group and H group).
      Values between two or more groups were compared by independent t-tests. RESULTS:
      In the liver and kidney, we found inflammatory infiltration in sepsis group while
      pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels
      increased while Bax mRNA and protein levels decreased in the liver and kidney of
      L, M and H groups. Serum IL-6, HMGB-1 and TNF-alpha levels decreased but IL-10
      level increased in L, M and H groups, compared to sepsis group. Compared to
      sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M
      and H groups. CONCLUSION: The administration of esmolol in early sepsis may
      reduce inflammation, inhibit apoptosis and protect key organs.

PMID- 28457763
TI  - Yankauer suction catheters with "safety" vent holes may impair safety in emergent
      airway management.

PMID- 28457764
TI  - Letter to the Editor regarding recent American Journal of Emergency Medicine
      article in press: "Point of care lung ultrasound of children with acute asthma
      exacerbations in the pediatric emergency department" by Dankoff et al.

PMID- 28457765
TI  - Cost savings associated with decreased emergency department utilization by
      reporting emergency department visits to specialists.

PMID- 28457766
TI  - Authors' response to commentary on: Point of care lung ultrasound of children
      with acute asthma exacerbations in the pediatric emergency department.

PMID- 28457767
TI  - Clinical and financial implications of emergency department visits for synthetic
      marijuana.
AB  - BACKGROUND: Many users believe that synthetic cannabinoids offer a safe and legal
      means of getting high. However, spikes in emergency department visits have been
      associated with use of synthetic cannabinoids. The purpose of the current study
      was to document emergency department visits from three large hospitals in one
      metropolitan area over a two month period. METHOD: This was a retrospective chart
      review examining 218 patients presenting to three inner city emergency
      departments between March and April 2014. Data collected included demographic
      information, information regarding ED diagnosis and treatment, signs and
      symptoms, ancillary testing, ED disposition, and cost of the medical treatment.
      RESULTS: The majority of patients (75.7%) were discharged after ED workup, but
      12.4% were admitted for medical treatment and 11.5% were admitted for psychiatric
      treatment. Ten patients (4.6%) were admitted to the ICU. Symptoms experienced
      most frequently include: hypertension, tachycardia, agitation, drowsiness,
      nausea, and confusion. Cluster analysis revealed four symptom clusters of
      individuals presenting after using synthetic cannabinoids: 1) confusion,
      hostility, agitation, 2) nausea, vomiting, abdominal pain, 3) drowsiness, and 4)
      the absence of these symptoms. CONCLUSION: This study has three important
      findings. First, significant ED resources are being used to treat individuals
      presenting due to effects of synthetic cannabis. Second, synthetic cannabis is
      not a benign substance. Third, while the hostile and agitated user is generally
      presented in the media, this study finds significant heterogeneity in
      presentation. Further research is needed to fully understand the implications of
      synthetic cannabinoid use.

PMID- 28457768
TI  - Feasibility and capacity for widespread use of emergency department-based home
      oxygen for Bronchiolitis.

PMID- 28457769
TI  - [Importance of the detection of dysphagia in geriatric patients].
AB  - INTRODUCTION: Oropharyngeal dysphagia is one of the lesser known geriatric
      syndromes, despite its enormous impact on functional capacity, quality of life,
      and health of those affected. MATERIAL AND METHODS: A descriptive and prospective
      study was conducted by the Geriatric Department of Barbastro Hospital (Huesca),
      from March 2012 to October 2014, as biannual and annual reviews in October 2015.
      This study included all patients on whom a volume-viscosity clinical examination
      (MECV-V test) was performed to suspecting dysphagia. RESULTS: The study included
      266 patients with a mean age of 82.35+/-12.3 years, and with a mean Barthel index
      score of 20.5+/-25.4, and mean Charlson index of 1.77+/-1.6. The test was
      performed in 105 cases after stroke (40%), 53 in dementia (20%), 24 in
      Parkinsonism (9%), and for other different reasons in 80 (31%). Dysphagia was
      diagnosed in 228 (86%) cases. Enteral nutrition was given in 25 (10.9%) cases.
      The test results were shown in the discharge report in 45% of the tests with
      positive result. The mean survival obtained after test in the patients who died
      was 230.8+/-256.5 days. Differences in survival at 12 months were found in
      patients with positive test, without finding a clear relationship with functional
      status and comorbidity. CONCLUSIONS: Dysphagia has a significant mortality, and
      the use of thickeners after its detection should be properly reported.

PMID- 28457770
TI  - [Anti-synthetase syndrome].

PMID- 28457771
TI  - [Vitamin B12 levels in the patient population attending an urban health centre in
      Madrid].
AB  - INTRODUCTION: Vitamin B12 levels are usually measured in Primary Care when the
      patients have symptoms or risk factors associated with its deficiency, mostly in
      the elderly. However, no evidence has been found to support the recommendation of
      screening in the general population. The aim of this study is to assess the
      relevance of having extended the screening of vitamin B12 deficiency to a younger
      population, after observing an increase in the prescription of this injected
      vitamin in a population under 65 years, by analysing the vitamin B12 values
      obtained. MATERIAL AND METHOD: A descriptive, retrospective, observational study
      was conducted on a sample consisting of 5,531 patients from Barajas Health
      Primary Centre, Madrid, between 2008 and 2012, and on whom a blood test was
      performed for any reason, with values of vitamin B12. RESULTS: A deficiency was
      found in 9.1% (SD 2.3) of the patients, of whom 49.4% were less than 65 years.
      The deficiencies were associated (P<.001, 95% CI) with age, dementia, changes in
      blood red cell counts, memory, and with the taking of metformin and proton pump
      inhibitors (P=.007). CONCLUSION: The prevalence of vitamin B12 deficiency in our
      served population is similar in patients older and younger than 65 years. The
      extended screening was relevant.

PMID- 28457772
TI  - [Jugular murmur as a multinodular goiter marker].

PMID- 28457773
TI  - Effective assessment of psychotropic medication side effects using PsyLOG mobile
      application.

PMID- 28457774
TI  - Sensory prediction errors in the continuum of psychosis.
AB  - Sensory prediction errors are fundamental brain responses that signal a violation
      of expectation in either the internal or external sensory environment, and are
      therefore crucial for survival and adaptive behaviour. Patients with
      schizophrenia show deficits in these internal and external sensory prediction
      errors, which can be measured using electroencephalography (EEG) components such
      as N1 and mismatch negativity (MMN), respectively. New evidence suggests that
      these deficits in sensory prediction errors are more widely distributed on a
      continuum of psychosis, whereas psychotic experiences exist to varying degrees
      throughout the general population. In this paper, we review recent findings in
      sensory prediction errors in the auditory domain across the continuum of
      psychosis, and discuss these in light of the predictive coding hypothesis.

PMID- 28457775
TI  - Experiences of rural and remote nurses assisting with disasters.
AB  - BACKGROUND: Globally, disasters are on the rise. Nurses play a significant role
      in responding to such events but little is known about rural and remote nurses'
      experiences. METHODS: A national cross-sectional survey of regulated nurses
      (registered nurses, registered psychiatric nurses, licensed practical nurses and
      nurse practitioners) in rural and remote Canada provided the data (n=2465) for
      the logistic regression of predictors of assisting with a disaster event within
      the last five years. The types of disaster events were also examined and open
      ended responses were explored to reveal nurses' perspectives. RESULTS: Nurse
      type, age, region of employment, employment status, number of rural communities
      worked, distance to advanced referral centre, remote community, personal
      professional boundaries, burnout and work engagement were significant factors
      related to assisting with a disaster event. Open-ended data alluded to the
      importance of pre-disaster preparation, and the difficulties experienced when
      personal-professional relationships are impacted during a disaster. CONCLUSIONS:
      Nursing education curricula needs to include information about disasters and the
      nurse's role. Continuing education opportunities and preparation for nurses
      should be offered in the workplace. Psychosocial supports to assist rural nurses
      who attend to disasters in their workplace will help them deal with issues such
      as the blurring of personal-professional relationships.

PMID- 28457776
TI  - Porcelain Aorta in a Patient Undergoing Coronary Artery Bypass Grafting Surgery.

PMID- 28457777
TI  - Antifibrinolytic Agents in Cardiac and Noncardiac Surgery: A Comprehensive
      Overview and Update.

PMID- 28457778
TI  - Unilateral Dilated Fixed Pupil after Thoracic Surgery: Need for Concern?

PMID- 28457780
TI  - Aortic Leaflet Billowing as a Risk Factor for Repair Failure After Aortic Valve
      Repair.

PMID- 28457779
TI  - Central Venous-to-Arterial Carbon Dioxide Partial Pressure Difference in Patients
      Undergoing Cardiac Surgery is Not Related to Postoperative Outcomes.
AB  - OBJECTIVE: The objective of this study was to assess the association between
      increased central venous-to-arterial carbon dioxide difference (DeltaPCO2)
      following cardiac surgery with cardiopulmonary bypass and postoperative morbidity
      and mortality. DESIGN: A prospective, observational, non-interventional study.
      PATIENTS: Three hundred ninety-three patients undergoing cardiac surgery with
      cardiopulmonary bypass. INTERVENTIONS: The primary endpoint was the occurrence of
      one or more major postoperative complications. A DeltaPCO2 >= 6 mmHg was
      considered to be abnormal. Data were first analyzed globally, and then according
      to 4 subgroups based on time course of DeltaPCO2 during the study period: [(1)
      persistently normal DeltaPCO2; (2) increasing DeltaPCO2; (3) decreasing
      DeltaPCO2; and (4) persistently high DeltaPCO2]. RESULTS: A total of 238 of the
      393 (61%) patients developed complications. The major postoperative complication
      rate did not differ among the 4 groups: 64% (n = 9) in group 1, 62% (n = 21) in
      group 2, 53% (n = 32) in group 3, and 62% (n = 176) in group 4 (p = 0.568).
      Mortality rates did not differ among the 4 groups (p > 0.05). DeltaPCO2 was
      correlated weakly with perfusion parameters. CONCLUSIONS: These results suggested
      that DeltaPCO2 is not predictive of postoperative complications or mortality.

PMID- 28457781
TI  - Myocardial Protection During Minimally Invasive Aortic Valve Replacement.

PMID- 28457782
TI  - Immediate Closure of Iatrogenic ASD After MitraClip Procedure Prompted by Acute
      Right Ventricular Dysfunction.

PMID- 28457783
TI  - Development of a robust, higher throughput green fluorescent protein (GFP)-based
      Epstein-Barr Virus (EBV) micro-neutralization assay.
AB  - The goal of most prophylactic vaccines is to elicit robust and effective
      neutralizing antibodies against the human pathogen target. The titer of
      neutralizing antibodies to Epstein-Barr Virus (EBV) is a useful biomarker for
      evaluating EBV vaccines. Here, the development and optimization of a 96-well
      micro-neutralization fluorescent imaging assay (FIA) using an EBV virus-encoding
      green fluorescent protein (GFP) to infect adherent EBV recipient cells is
      reported. The conditions were optimized for generating reproducible EBV-GFP
      virus, for maintaining viral infectivity for months, and for efficient viral
      infection of recipient cell culture. The utility of the EBV-GFP FIA
      neutralization assay was demonstrated in a mouse study of an investigational
      adjuvanted EBV gp350 subunit vaccine. This assay confirmed the generation of high
      titers of anti-EBV-neutralizing antibodies which correlated well with the
      established Raji cell-based flow cytometry-based EBV neutralization assay, as
      well as with anti-gp350 IgG titers. In naturally infected EBV+ human serum
      samples, a good correlation between anti-gp350 IgG ELISA titer and EBV-GFP FIA
      neutralization antibody titer was also observed. Taken together, these results
      demonstrate the establishment of a scalable high throughput EBV-GFP FIA micro
      neutralization assay suitable to measure humoral EBV vaccine response in a large
      scale human trial.

PMID- 28457784
TI  - Laboratory validation of two real-time RT-PCR methods with 5'-tailed primers for
      an enhanced detection of foot-and-mouth disease virus.
AB  - The 3D and 5UTR real-time RT-PCR assays (RT-qPCR) from Callahan et al. (2002) and
      Reid et al. (2002) are commonly used reference methods for the detection of foot
      and-mouth disease virus (FMDV). For an optimal detection of FMDV in clinical
      samples, it is advised to use both assays simultaneously (King et al., 2006).
      Recently, Vandenbussche et al. (2016) showed that the addition of 5'-tails to the
      FMDV-specific primers enhances the detection of FMDV in both the 3D and the 5UTR
      RT-qPCR assay. To validate the 3D and 5UTR RT-qPCR assays with 5'-tailed primers
      for diagnostic purposes, both assays were run in parallel in a triplex one-step
      RT-qPCR protocol with beta-actin as an internal control and synthetic RNA as an
      external control. We obtained low limits of detection and high linearity's, high
      repeatability and reproducibility, near 100% analytical specificity and >99%
      diagnostic accuracy for both assays. It was concluded that the 3D and 5UTR RT
      qPCR assays with 5'-tailed primers are particularly suited for the detection of
      FMDV as well as to exclude the presence of FMDV.

PMID- 28457785
TI  - Detection of chikungunya viral RNA in mosquito bodies on cationic (Q) paper based
      on innovations in synthetic biology.
AB  - Chikungunya virus (CHIKV) represents a growing and global concern for public
      health that needs inexpensive and convenient methods to collect mosquitoes as
      potential carriers so that they can be preserved, stored and transported for
      later and/or remote analysis. Reported here is a cellulose-based paper,
      derivatized with quaternary ammonium groups ("Q-paper") that meets these needs.
      In a series of tests, infected mosquito bodies were squashed directly on Q-paper.
      Aqueous ammonia was then added on the mosquito bodies to release viral RNA that
      adsorbed on the cationic surface via electrostatic interactions. The samples were
      then stored (frozen) or transported. For analysis, the CHIKV nucleic acids were
      eluted from the Q-paper and PCR amplified in a workflow, previously developed,
      that also exploited two nucleic acid innovations, ("artificially expanded genetic
      information systems", AEGIS, and "self-avoiding molecular recognition systems",
      SAMRS). The amplicons were then analyzed by a Luminex hybridization assay. This
      procedure detected CHIKV RNA, if present, in each infected mosquito sample, but
      not in non-infected counterparts or ddH2O samples washes, with testing one week
      or ten months after sample collection.

PMID- 28457786
TI  - Gamma camera calibrations for the Italian multicentre study for lesion dosimetry
      in 223Ra therapy of bone metastases.
AB  - PURPOSE: The aim was to calibrate gamma cameras in the framework of the Italian
      multicentre study for lesion dosimetry in 223Ra therapy of bone metastases.
      Equipments of several manufacturers and different models were used. METHODS:
      Eleven gamma cameras (3/8- and 5/8-inch crystal) were used, acquiring planar
      static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The
      sensitivity was measured in air, varying source-detector distance and source
      size. Transmission curves were measured, calculating the parameters used for
      attenuation/scatter correction with the pseudo-extrapolation number method, and
      assessing their variations with the source size. RESULTS: Values of the
      calibration factor (geometric mean of both detector sensitivities) ranged from
      41.1 to 113.9cps/MBq. For the smallest source (diameter of 3.5cm), the
      calibration factor decrease ranged from -30% to -4%, highlighting the importance
      of partial volume effects according to the equipment involved. The sensitivity
      variation with the source-detector distance, with respect to the 15cm-value,
      reached 10% (in absolute value) in the range 5-30cm, but fixing the distance
      between the two heads, the calibration factor variation with the distance from
      the midline was within 3.6%. Appreciable variation of the transmission curves
      with the source size were observed, examining the results obtained with six gamma
      cameras. CONCLUSION: Assessments of sensitivity and transmission curve variations
      with source size should be regularly implemented in calibration procedures. The
      results of this study represent a useful compendium to check the obtained
      calibrations for dosimetric purposes.

PMID- 28457787
TI  - Time resolved dose rate distributions in brachytherapy.
AB  - PURPOSE: To investigate the biological significance of introducing time-resolved
      dose rate distributions (TR-DRD) in brachytherapy. MATERIALS AND METHODS: The
      treatment plan of a head and neck patient treated with pulsed-dose-rate (PDR)
      brachytherapy was considered. The TR-DRD was calculated on the basis of a Monte
      Carlo generated single source dose rate matrix taking into account the dose rate
      per source dwell position. Biologically Effective Dose (BED) was obtained
      considering either the mean dose rate per pulse (analytical method) or the TR-DRD
      (numerical method). Corresponding Tumor Control Probabilities (TCP) were
      calculated and compared for various PDR schemes and repair half-times from the
      literature. The dose of the biologically equivalent high-dose-rate (HDR)
      treatment schedule was also evaluated. RESULTS: The analytical method presents an
      overall BED underestimation (up to 2%) relative to TR-DRD results. This is
      associated with an analytical-based TCP underestimation which increases with
      dose/pulse, pulse duration and period time and decreases with total dose. The
      half-time of repair seems to have the largest impact on the TCP calculations,
      with significant differences (up to 39.1%) corresponding to the shorter repair
      half-times. Regarding the equivalent HDR treatment schedule, the analytical
      method resulted to a HDR isoeffective dose underestimation lower than 2.2% and
      thus does not warrant any change in the derivation of the equivalent HDR scheme.
      CONCLUSION: TR-DRD data should be taken into account for PDR biological
      effectiveness estimations, especially for short tissue repair half-times. This
      does not appear however to influence dose prescription of the equivalent HDR
      treatment schedule for mobile tongue carcinoma.

PMID- 28457788
TI  - Radiological protection for pregnant women at a large academic medical Cancer
      Center.
AB  - PURPOSE: Most radiation protection programs, regulations and guidance apply
      specific restrictions to the occupational exposure of pregnant workers. The aim
      of this study was to compile data from the declared pregnant woman (DPW)
      radiation protection program over more than 5years at a large, high-volume,
      comprehensive oncology academic/medical institution and to evaluate for
      effectiveness against existing regulations and guidance. METHODS: A retrospective
      review was performed of the data collected as part of the DPW radiation
      protection program from January 2010 through May 2016, including the number of
      declared pregnancies, worker category, personal and fetal dosimetry monitoring
      measurements, workplace modifications, as well as the monthly and total recorded
      badge results during the entire pregnancy. RESULTS: 245 pregnancies were
      declared. The mean monthly fetal radiation dosimetry result was 0.009mSv with a
      median of 0.005mSv and a maximum of 0.39mSv. The mean total dose over the entire
      pregnancy was estimated to be 0.08mSv with a median of 0.05mSv and a maximum of
      0.89mSv. Only 8 (3.2%) of the 245 declared pregnancies required that workplace
      modifications be implemented for the worker. CONCLUSIONS: The implementation of a
      declared pregnancy and fetal assessment program, careful planning, an
      understanding of the risks, and minimization of radiation dose by employing
      appropriate radiation safety measures as needed, can allow medical staff to
      perform procedures and normal activities without incurring significant risks to
      the conceptus, or significant interruptions of job activities for most medical
      workers.

PMID- 28457789
TI  - Lateral thinking - Interocular symmetry and asymmetry in neurovascular
      patterning, in health and disease.
AB  - No biological system or structure is likely to be perfectly symmetrical, or have
      identical right and left forms. This review explores the evidence for eye and
      visual pathway asymmetry, in health and in disease, and attempts to provide
      guidance for those studying the structure and function of the visual system,
      where recognition of symmetry or asymmetry may be essential. The principal
      question with regards to asymmetry is not 'are the eyes the same?', for some
      degree of asymmetry is pervasive, but 'when are they importantly different?'.
      Knowing if right and left eyes are 'importantly different' could have significant
      consequences for deciding whether right or left eyes are included in an analysis
      or for examining the association between a phenotype and ocular parameter. The
      presence of significant asymmetry would also have important implications for the
      design of normative databases of retinal and optic nerve metrics. In this review,
      we highlight not only the universal presence of asymmetry, but provide evidence
      that some elements of the visual system are inherently more asymmetric than
      others, pointing to the need for improved normative data to explain sources of
      asymmetry and their impact on determining associations with genetic,
      environmental or health-related factors and ultimately in clinical practice.

PMID- 28457790
TI  - Initial Assessment and Triage of the Stroke Patient.
AB  - Nearly 800,000 strokes occur in the United States each year, and stroke is the
      leading cause of preventable permanent disability. Timely recognition and
      treatment are imperative to reduce stroke-related morbidity and mortality. Given
      the evidence supporting intravenous thrombolysis and mechanical thrombectomy for
      ischemic stroke, stroke symptoms must be rapidly identified and mimics quickly
      excluded prior to therapeutic decisions. Intravenous tissue plasminogen activator
      is recommended for all qualified patients and patients with presentations
      suggesting large vessel occlusion should be evaluated for mechanical
      thrombectomy. Time to treatment is the most important prognostic factor for
      clinical outcome, highlighting the importance of reliable and efficient local and
      regional systems of care.

PMID- 28457791
TI  - Left Atrial Appendage Occlusion for Stroke Prevention.
AB  - More than 2.3 million adults in the United States have atrial fibrillation (AF),
      which exposes them to a 5-fold increased risk of stroke. The left atrial
      appendage (LAA) appears to be the source of thrombus formation in the vast
      majority of these patients. Anticoagulation significantly reduces the risk of
      stroke, but often we encounter patients who have absolute or relative
      contraindication to anticoagulation. Percutaneous LAA exclusion offers an
      alternative to anticoagulation to decrease the risk of stroke. Three device
      systems are currently available in the United States. The WATCHMAN(r) device is
      the most studied and approved by Food and Drug Administration (FDA) to be used in
      patients with AF unsuitable for anticoagulation who are at a high risk of stroke.
      The Amulet(r) device is currently being used as part of the AMPLATZER(r)
      Amulet(r) LAA Occluder trial, which is a non-inferiority randomized trial
      comparing the Amulet(r) to the WATCHMAN(r) device. The third device in use is the
      LARIAT(r), which is an FDA approved snare and pre-tied stich system. It is used
      to approximate soft tissue which in this case is the LAA. It is a hybrid system
      and requires both epicardial and endocardial access. The main obstacle to
      percutaneous LAA closure is procedural related complications, which can be
      minimized with optimum operator experience.

PMID- 28457792
TI  - A Gene Regulatory Network Balances Neural and Mesoderm Specification during
      Vertebrate Trunk Development.
AB  - Transcriptional networks, regulated by extracellular signals, control cell fate
      decisions and determine the size and composition of developing tissues. One
      example is the network controlling bipotent neuromesodermal progenitors (NMPs)
      that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue.
      Here, we use single-cell transcriptomics to identify the molecular signature of
      NMPs and reverse engineer the mechanism that regulates their differentiation.
      Together with genetic perturbations, this reveals a transcriptional network that
      integrates opposing retinoic acid (RA) and Wnt signals to determine the rate at
      which cells enter and exit the NMP state. RA, produced by newly generated
      mesodermal cells, provides feedback that initiates NMP generation and induces
      neural differentiation, thereby coordinating the production of neural and
      mesodermal tissue. Together, the data define a regulatory network architecture
      that balances the generation of different cell types from bipotential progenitors
      in order to facilitate orderly axis elongation.

PMID- 28457794
TI  - Partial quadriceps tendon transfer for revision medial patellofemoral ligament
      reconstruction: A new surgical technique.
AB  - Medial patellofemoral ligament (MPFL) reconstruction for patellofemoral
      instability is a common procedure. Although MPFL reconstruction is a successful
      procedure in terms of return to normal life or sports, revision cases are
      challenging due to previous holes into the patella or implants placed in the
      anatomical femoral insertion site. In this technical note, the use of a partial
      quadriceps tendon transfer to the adductor magnus tendon is presented as a good
      solution for revision cases to avoid the use of implants, bone drilling, use of
      allografts, or two-stage surgical procedures. In addition, this procedure could
      be also used as a primary procedure in skeletally immature patients.

PMID- 28457795
TI  - Pseudoaneurysm of the deep femoral artery caused by a guide wire following femur
      intertrochanteric fracture with a hip nail: A case report.
AB  - An 85-year-old woman developed severe swelling and pain in the proximal thigh
      after internal fixation of an intertrochanteric fracture of the femur with a hip
      nail. In order to identify the causes and determine the effective treatment,
      angiography was performed. The results of the angiography revealed a
      pseudoaneurysm of a branch of deep femoral artery. Endovascular embolization was
      used to treat the pseudoaneurysm. After reviewing all possible causes, we found a
      mistake in insertion of a guide wire for hip nail. Using intraoperative
      fluoroscopic images, we found the mal-positioned guide wire located posterior to
      trochanter on lateral view of hip. This case study reminds us that pseudoaneurysm
      can occur in a guide wire during hip nailing. Surgeons can avoid this
      complication with confirmation of lateral and anteroposterior view of hip.

PMID- 28457793
TI  - Multi-site Neurogenin3 Phosphorylation Controls Pancreatic Endocrine
      Differentiation.
AB  - The proneural transcription factor Neurogenin3 (Ngn3) plays a critical role in
      pancreatic endocrine cell differentiation, although regulation of Ngn3 protein is
      largely unexplored. Here we demonstrate that Ngn3 protein undergoes cyclin
      dependent kinase (Cdk)-mediated phosphorylation on multiple serine-proline sites.
      Replacing wild-type protein with a phosphomutant form of Ngn3 increases alpha
      cell generation, the earliest endocrine cell type to be formed in the developing
      pancreas. Moreover, un(der)phosphorylated Ngn3 maintains insulin expression in
      adult beta cells in the presence of elevated c-Myc and enhances endocrine
      specification during ductal reprogramming. Mechanistically, preventing multi-site
      phosphorylation enhances both Ngn3 stability and DNA binding, promoting the
      increased expression of target genes that drive differentiation. Therefore, multi
      site phosphorylation of Ngn3 controls its ability to promote pancreatic endocrine
      differentiation and to maintain beta cell function in the presence of pro
      proliferation cues and could be manipulated to promote and maintain endocrine
      differentiation in vitro and in vivo.

PMID- 28457797
TI  - Correction to Lancet HIV 2017; 4: e284-94.

PMID- 28457796
TI  - Volar dislocation of the metacarpophalangeal joint of the thumb: A case report.
AB  - We present an 18 year-old patient with a volar dislocation of the
      metacarpophalangeal joint of the thumb. Open reduction was performed through a
      dorsal incision. Because of the soft tissue interposition such as dorsal capsule,
      volar plate, dislocated extensor pollicis longus and brevis tendons, ruptured
      ulnar collateral ligament; open reduction, soft tissue and ligament repair are
      recommended for this type of thumb dislocations.

PMID- 28457798
TI  - Cardiology Consultation in the Emergency Department Reduces Re-hospitalizations
      for Low-Socioeconomic Patients with Acute Decompensated Heart Failure.
AB  - BACKGROUND: Re-hospitalization after discharge for acute decompensated heart
      failure is a common problem. Low-socioeconomic urban patients suffer high rates
      of re-hospitalization and often over-utilize the emergency department (ED) for
      their care. We hypothesized that early consultation with a cardiologist in the ED
      can reduce re-hospitalization and health care costs for low-socioeconomic urban
      patients with acute decompensated heart failure. METHODS: There were 392 patients
      treated at our center for acute decompensated heart failure who received
      standardized education and follow-up. Patients who returned to the ED received
      early consultation with a cardiologist; 392 patients who received usual care
      served as controls. Thirty- and 90-day re-hospitalization, ED re-visits, heart
      failure symptoms, mortality, and health care costs were recorded. RESULTS:
      Despite guideline-based education and follow-up, the rate of ED re-visits was not
      different between the groups. However, the rate of re-hospitalization was
      significantly lower in patients receiving the intervention compared with controls
      (odds ratio 0.592), driven by a reduction in the risk of readmission from the ED
      (0.56 vs 0.79, respectively). Patients receiving the intervention accumulated 14%
      fewer re-hospitalized days than controls and 57% lower 30-day total health care
      cost. Despite the reduction in health care resource consumption, mortality was
      unchanged. After accounting for the total cost of intervention delivery, the
      health care cost savings was substantially greater than the cost of intervention
      delivery. CONCLUSION: Early consultation with a cardiologist in the ED as an
      adjunct to guideline-based follow-up is associated with reduced re
      hospitalization and health care cost for low-socioeconomic urban patients with
      acute decompensated heart failure.

PMID- 28457799
TI  - Dietary treatment of fatty liver: High dietary protein content has an
      antisteatotic and antiobesogenic effect in mice.
AB  - Few studies have assessed the effect of changing ratios of dietary macronutrients
      on fat accumulation in adipose tissue and organs such as the liver in a 3*n(n>=3)
      factorial design. We investigated the effects of 7 diets from a single
      manufacturer containing 11-58en% protein (casein), 0-81en% carbohydrates (CHO;
      sucrose, maltrodextrin-10 and corn starch), and 8-42en% fat (triheptanoin, olive
      oil or cocoa butter) in C57BL/6J mice, a good model for diet-induced obesity and
      fatty liver. The diets were fed for 3weeks to wild-type and hyperlipidemic male
      and female mice. Caloric intake was mainly determined by dietary fat. Body
      weight, liver lipid and cholesterol content, NFkappaB activation, and fat-pad
      size decreased only in mice fed a high-protein diet. A high dietary protein:CHO
      ratio reduced plasma FGF21 concentration, and increased liver PCK1 protein
      content and plasma triglyceride concentration. The dietary protein:CHO ratio
      determined hepatic expression of Pck1 and Ppargc1a in males, and Fgf21 in
      females, whereas the dietary CHO:fat ratio determined that of Fasn, Acaca1, and
      Scd1 in females. Hepatic glycogen content was determined by all three dietary
      components. Both hepatic PCK1 and plasma FGF21 correlated strongly and inversely
      with hepatic TG content, suggesting a key role for PCK1 and increased
      gluconeogenesis in resolving steatosis with a high-protein diet, with FGF21
      expression reflecting declining cell stress. We propose that a diet containing
      ~35en% protein, 5-10en% fat, and 55-60en% carbohydrate will prevent fatty liver
      in mice without inducing side effects.

PMID- 28457800
TI  - Corrigendum to "Prevalence and predictors of obstructive sleep apnea in young
      children with Down syndrome" [Sleep Med 27-28 (2016) 99-106].

PMID- 28457801
TI  - Restless leg syndrome and periodic limb movements in sleep: risk for
      cardiovascular disease.

PMID- 28457803
TI  - Evaluation of Urinary Aquaporin 2 and Plasma Copeptin as Biomarkers of
      Effectiveness of Desmopressin Acetate for the Treatment of Monosymptomatic
      Nocturnal Enuresis.
AB  - PURPOSE: Desmopressin is a synthetic V2 specific analogue of antidiuretic hormone
      (arginine vasopressin) that is widely used as first line treatment for
      monosymptomatic nocturnal enuresis. However, no biomarkers to predict
      desmopressin effectiveness have yet been established. Because arginine
      vasopressin is unstable, we prospectively measured the major urine concentration
      factor aquaporin 2 and serum copeptin (as a surrogate marker for vasopressin) in
      patients with monosymptomatic nocturnal enuresis, and evaluated whether they are
      useful for predicting desmopressin treatment outcome. MATERIALS AND METHODS: The
      study included 32 children 6 to 11 years old with monosymptomatic nocturnal
      enuresis and nocturnal polyuria. Exclusion criteria were daytime urinary symptoms
      and underlying diseases causing nocturnal enuresis. Subjects were treated with
      120 MUg or 240 MUg desmopressin oral disintegrating tablet and were divided into
      responders (at 120 or 240 MUg) and nonresponders (at 240 MUg). Day/night ratios
      of plasma copeptin and urinary aquaporin 2 were measured during desmopressin
      treatment. RESULTS: There was no significant difference in baseline day/night
      ratio of urinary aquaporin 2 between desmopressin responders and nonresponders.
      After 8 weeks of treatment there was a significant correlation between day/night
      ratio of aquaporin 2 and percentage of wet nights. In responders (but not
      nonresponders) there was a significant difference in the change in aquaporin 2
      day/night ratio from before treatment to complete remission (p = 0.0004). For
      plasma copeptin the baseline day/night ratio for responders at 120 MUg was
      significantly lower than in the 240 MUg nonresponder group (p = 0.02).
      CONCLUSIONS: Urinary aquaporin 2 appears to be a biomarker of desmopressin
      treatment effectiveness during therapy, while plasma copeptin levels before
      treatment are predictive of desmopressin response.

PMID- 28457802
TI  - Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Identify
      Clear Cell Renal Cell Carcinoma in cT1a Renal Masses.
AB  - PURPOSE: The detection of small renal masses is increasing with the use of cross
      sectional imaging, although many incidental lesions have negligible metastatic
      potential. Among malignant masses clear cell renal cell carcinoma is the most
      prevalent and aggressive subtype. A method to identify such histology would aid
      in risk stratification. Our goal was to evaluate a likelihood scale for
      multiparametric magnetic resonance imaging in the diagnosis of clear cell
      histology. MATERIALS AND METHODS: We retrospectively reviewed the records of
      patients with cT1a masses who underwent magnetic resonance imaging and partial or
      radical nephrectomy from December 2011 to July 2015. Seven radiologists with
      different levels of experience who were blinded to final pathology findings
      independently reviewed studies based on a predefined algorithm. They applied a
      clear cell likelihood score, including 1-definitely not, 2-probably not, 3
      equivocal, 4-probably and 5-definitely. Binary classification was used to
      determine the accuracy of clear cell vs all other histologies. Interobserver
      agreement was calculated with the weighted kappa statistic. RESULTS: A total of
      110 patients with 121 masses were identified. Mean tumor size was 2.4 cm and 50%
      of the lesions were clear cell. Defining clear cell as scores of 4 or greater
      demonstrated 78% sensitivity and 80% specificity while scores of 3 or greater
      showed 95% sensitivity and 58% specificity. Interobserver agreement was moderate
      to good with a mean kappa of 0.53. CONCLUSIONS: A clear cell likelihood score
      used with magnetic resonance imaging can reasonably identify clear cell histology
      in small renal masses and may decrease the number of diagnostic renal mass
      biopsies. Standardization of imaging protocols and reporting criteria is needed
      to improve interobserver reliability.

PMID- 28457804
TI  - The clinical pharmacology of non-sedating antihistamines.
AB  - We previously reported on brain H1 receptor occupancy measurements of
      antihistamines in human brain using [11C]doxepin and positron emission tomography
      (PET). We proposed the use of brain H1 receptor occupancy to classify
      antihistamines objectively into three categories of sedating, less-sedating, and
      non-sedating antihistamines according to their sedative effects. Non-sedating
      antihistamines are recommended for the treatment of allergies such as pollinosis
      and atopic dermatitis because of their low penetration into the central nervous
      system. Physicians and pharmacists are responsible for fully educating patients
      about the risks of sedating antihistamines from pharmacological points of view.
      If a sedating antihistamine must be prescribed, its sedative effects should be
      thoroughly considered before choosing the drug. Non-sedating antihistamines
      should be preferentially used whenever possible as most antihistamines are
      equally efficacious, while adverse effects of sedating antihistamines can be
      serious. This review summarizes the pharmacological properties of clinically
      useful non-sedating antihistamines from the perspective of histamine function in
      the CNS.

PMID- 28457806
TI  - Detection of spontaneous coronary artery spasm with optical coherence tomography
      in a patient with acute coronary syndrome.
AB  - We present 2 illustrative cases of acute coronary syndrome and spontaneous
      coronary artery spasm evaluated by optical coherence tomography. Different spasm
      patterns were showed by optical coherence tomography (OCT), according to whether
      there were underlying atherosclerotic plaques or not.

PMID- 28457805
TI  - Negative Affectivity, Aging, and Depression: Results From the Neurobiology of
      Late-Life Depression (NBOLD) Study.
AB  - OBJECTIVE: Neuroticism is a common yet understudied condition in older adults. We
      hypothesized that presence of high negativity affectivity (NA), a key feature of
      neuroticism, would be associated with different prefrontal cortex (PFC) activity
      and connectivity patterns in depressed and never-depressed older adults. METHODS:
      This is a baseline cross-sectional analysis of a cohort study of 52 depressed and
      36 never-depressed older adults. Assessments included NA scores from the Type D
      Scale-14 and Montgomery-Asberg Depression Rating Scale scores. All subjects had a
      3T brain functional magnetic resonance imaging resting scan, neuronal activity
      determined by amplitude of low-frequency fluctuations (ALFFs) were obtained, and
      resting state functional connectivity (FC) analyses were performed. Analyses of
      covariance were conducted on ALFFs and FC to examine significant differences
      between groups. RESULTS: In the ALFF analyses there were clearly different
      patterns between depressed and comparison groups in the correlation of ALFFs and
      NA. The correlation differences between the two groups were significant in the
      dorsomedial PFC, insula, amygdala, and posterior cingulate cortex (PCC). FC
      analyses revealed different between-group connectivity patterns. Significantly
      higher ventromedial PFC-amygdala FC with NA correlation was found in the
      depressed group than that in the never-depressed group. CONCLUSION: This study
      confirms differential activity of the dorsal and ventral regions of the medial
      PFC in individuals with high neuroticism. Our findings suggest increased rostral
      medial PFC activity may be a marker of resilience to depression in the elderly
      and decreased anterior ventromedial PFC, PCC, and amygdala activity may be a
      result of successful emotion regulation in never-depressed higher NA individuals.

PMID- 28457808
TI  - Toward a unified framework for research on instructions and other messages: An
      introduction to the special issue on the power of instructions.
AB  - Instructions are known to have a profound impact on human behavior. Nevertheless,
      research on the effects of instructions is relatively scarce and scattered across
      different areas of research in psychology and neuroscience. The current issue of
      this journal contains six papers that review research on instructions in
      different research areas. In this introduction to the special issue, we provide
      the outline of a framework that focuses on five components that can be varied in
      research on this topic (sender, message, receiver, context, and outcome). The
      framework brings order to the boundless potential variability in research on the
      effects of messages (i.e., it has heuristic value) and highlights that past
      research explored only a tiny fraction of what is possible (i.e., it has
      predictive value). Moreover, it reveals that research in different areas tends to
      examine different instantiations of the five components. The latter observation
      implies that much can be gained from closer interactions between researchers from
      different areas.

PMID- 28457807
TI  - Safety and efficacy of anti-thrombotic regimens in patients with percutaneous
      coronary intervention requiring oral anticoagulation: A traditional and network
      meta-analysis.
AB  - BACKGROUND: Previous reports have been inconsistent in generating a consensus for
      optimal treatment strategy for patients with percutaneous coronary intervention
      (PCI) who also require oral anticoagulation (OAC). We conducted a traditional and
      network meta-analysis to evaluate the safety and efficacy of anti-thrombotic
      regimens in this subset of patients. METHODS: 30 articles were recovered through
      preferred reporting items for systematic reviews and meta-analyses (PRISMA) using
      MEDLINE, EMBASE and Cochrane Central Register of Controlled Clinical Trials
      (CENTRAL) from inception to December 2016. RESULTS: Dual antiplatelet therapy
      (DAPT) was found to be the safest treatment modality when compared to triple
      therapy (TT) or combination of OAC and single antiplatelet agent (OAC+SAP) [Major
      bleeding: (DAPT vs OAC+SAP: odds ratio (OR), 0.53; 95% credible interval (CrI),
      0.30-0.91) (DAPT vs TT: OR, 0.45; 95% CrI, 0.31-0.64)]. There were no significant
      differences in major adverse cardiovascular events (MACE), myocardial infarction
      (MI), cardiovascular (CV) or total survival, stent thrombosis or target vessel
      revascularization (TVR) amongst the three treatment arms. TT was ranked superior
      for stroke reduction (SUCRA, 69%) followed by OAC+SAP and DAPT. When traditional
      analysis was adjusted for randomized data, OAC+SAP was equivalent to TT with
      regards to stroke (OR, 0.74; 95% confidence interval (CI), 0.38-1.46; p=0.39) and
      showed significant reduction in MACE and total mortality. CONCLUSION: DAPT was
      found to be the safest and equally effective regimen when compared to TT and
      OAC+SAP. However this strategy bears considerable risk to patients with high
      thromboembolic risk. This issue can be encountered by using OAC+SAP as an
      alternative of TT in patients with intermediate to high stroke risk and
      intermediate to high bleeding propensity.

PMID- 28457810
TI  - Chronic stress suppresses anti-tumor TCD8+ responses and tumor regression
      following cancer immunotherapy in a mouse model of melanoma.
AB  - Animal tumor models and human cancer studies have provided convergent evidence
      that chronic psychological stress plays a decisive role in modulating anti-tumor
      T cell immunity. However, whether chronic stress also affects anti-cancer vaccine
      strategies that rely on the induction of functional tumor-specific TCD8+ cells
      has not been investigated yet. In this study we provide direct evidence that
      chronic stress suppresses the therapeutic efficacy of a biodegradable poly(d,l
      lactide-co-glycolide) microsphere (PLGA-MS) based cancer vaccine in a murine
      melanoma model. Exposure of mice to social disruption stress (SDR), a well
      established model mimicking psychological chronic stress in humans, significantly
      impaired tumor protection in response to cancer vaccination under both
      prophylactic and therapeutic conditions. Vaccine failure in stressed mice
      correlated with significantly reduced generation of interferon-gamma (IFN-gamma)
      producing TCD8+ effectors and CTL-mediated killing. Phenotypic analysis of
      dendritic cells (DCs) revealed that both migratory and lymphoid-resident DCs
      failed to undergo full maturation upon antigen uptake. Notably, decreased DC
      maturation was associated with a significant impairment of peripheral DCs to
      migrate to draining LNs and to prime subsequent TCD8+ responses in vivo. In
      conclusion, chronic stress represents an important factor mediating
      immunosuppression in cancer-vaccinated hosts by impairing DC functions and
      subsequent TCD8+ priming. Potentially, the mechanistic insights gained in this
      study open new avenues in utilizing the full potential of anti-cancer vaccination
      strategies.

PMID- 28457809
TI  - Circulating inflammatory biomarkers in relation to brain structural measurements
      in a non-demented elderly population.
AB  - The aim of this investigation was to determine whether circulating inflammatory
      biomarkers c-reactive protein (CRP), interleukin-6 (IL6), and alpha 1
      antichymotrypsin (ACT) were related to structural brain measures assessed by
      magnetic resonance imaging (MRI). High-resolution structural MRI was collected on
      680 non-demented elderly (mean age 80.1years) participants of a community-based,
      multiethnic cohort. Approximately three quarters of these participants also had
      peripheral inflammatory biomarkers (CRP, IL6, and ACT) measured using ELISA.
      Structural measures including brain volumes and cortical thickness (with both
      global and regional measures) were derived from MRI scans, and repeated MRI
      measures were obtained after 4.5years. Mean fractional anisotropy was used as the
      indicator of white matter integrity assessed with diffusion tensor imaging. We
      examined the association of inflammatory biomarkers with brain volume, cortical
      thickness, and white matter integrity using regression models adjusted for age,
      gender, ethnicity, education, APOE genotype, and intracranial volume. A doubling
      in CRP (b=-2.48, p=0.002) was associated with a smaller total gray matter volume,
      equivalent to approximately 1.5years of aging. A doubling in IL6 was associated
      with smaller total brain volume (b=-14.96, p<0.0001), equivalent to approximately
      9years of aging. Higher IL6 was also associated with smaller gray matter (b=
      6.52, p=0.002) and white matter volumes (b=-7.47, p=0.004). The volumes of most
      cortical regions including frontal, occipital, parietal, temporal, as well as
      subcortical regions including pallidum and thalamus were associated with IL6. In
      a model additionally adjusted for depression, vascular factors, BMI, and smoking
      status, the association between IL6 and brain volumes remained, and a doubling in
      ACT was marginally associated with 0.054 (p=0.001) millimeter thinner mean
      cortical thickness, equivalent to that of approximately 2.7years of aging. None
      of the biomarkers was associated with mean fractional anisotropy or longitudinal
      change of brain volumes and thickness. Among older adults, increased circulating
      inflammatory biomarkers were associated with smaller brain volume and cortical
      thickness but not the white matter tract integrity. Our preliminary findings
      suggest that peripheral inflammatory processes may be involved in the brain
      atrophy in the elderly.

PMID- 28457811
TI  - Methylene blue attenuates neuroinflammation after subarachnoid hemorrhage in rats
      through the Akt/GSK-3beta/MEF2D signaling pathway.
AB  - Subarachnoid hemorrhage (SAH) is a serious medical problem with few effective
      pharmacotherapies available, and neuroinflammation has been identified as an
      important pathological process in early brain injury (EBI) after SAH. Methylene
      blue (MB) is an older drug that has been recently proven to exert extraordinary
      neuroprotective effects in several brain insults. However, no study has reported
      the beneficial effects of MB in SAH. In the current investigation, we studied the
      neuroprotective effects of MB in EBI after SAH and focused on its anti
      inflammatory role. A total of 303 rats were subjected to an endovascular
      perforation process to produce an SAH model. We found that MB could significantly
      ameliorate brain edema secondary to BBB disruption and alleviate neurological
      dysfunction after SAH. MB administration also promoted the phosphorylation of Akt
      and GSK-3beta, leading to an increased concentration of MEF2D in the nucleus. The
      cytokine IL-10 was up-regulated, and IL-1beta, IL-6 and TNF-alpha were down
      regulated after MB administration. MB administration could also alleviate
      neutrophil infiltration and microglia activation after SAH. MK2206, a selective
      inhibitor of Akt, abolished the neuroprotective effects of MB, inhibited the
      phosphorylation of Akt and prevented the nuclear localization of MEF2D. MK2206
      also reduced the expression of IL-10 and increased the expression of pro
      inflammatory cytokines. In conclusion, these data suggested that MB could
      ameliorate neuroinflammatory responses after SAH, and its anti-inflammatory
      effects might be exerted via activation of the Akt/GSK-3beta/MEF2D pathway.

PMID- 28457812
TI  - The RECALCAR Project. Healthcare in the Cardiology Units of the Spanish National
      Health System, 2011 to 2014.
AB  - The RECALCAR project (Spanish acronym for Resources and Quality in Cardiology
      Units) uses 2 data sources: a survey of cardiology units and an analysis of the
      Minimum Basic Data set of all hospital discharges of the Spanish National Health
      System. From 2011 to 2014, there was marked stability in all indicators of the
      availability, utilization, and productivity of cardiology units. There was
      significant variability between units and between the health services of the
      autonomous communities. There was poor implementation of process management (only
      14% of the units) and scarce development of health care networks (17%).
      Structured cardiology units tended to have better results, in terms of both
      quality and efficiency. No significant differences were found between the
      different types of unit in the mean length of stay (5.5+/-1.1 days) or the ratio
      between successive and first consultations (2:1). The mean discharge rate was
      5/1000 inhabitants/y and the mean rate of initial consultations was 16+/-4/1000
      inhabitants/y. No duty or on-call cardiologist was available in 30% of cardiology
      units with 24 or more beds; of these, no critical care beds were available in
      45%. Our findings support the recommendation to regionalize cardiology care and
      to promote the development of cardiology unit networks.

PMID- 28457813
TI  - High-definition Intravascular Ultrasound Vs Optical Coherence Tomography:
      Preliminary Experience.

PMID- 28457814
TI  - Persistent Untreated Screening-Detected Breast Cancer: An Argument Against
      Delaying Screening or Increasing the Interval Between Screenings.
AB  - PURPOSE: The aim of this study was to investigate the natural history of
      untreated screen-detected breast cancer. METHODS: A prospective cohort survey of
      Society of Breast Imaging fellows concerning the appearance on subsequent
      mammography of untreated breast cancer detected on screening mammography was
      conducted. RESULTS: A representative sample of the 108 actively practicing
      Society of Breast Imaging fellows (n = 42 [39%]) participated, each reporting
      outcomes data from his or her entire screening mammography practice. Among all
      practices, 25,281 screen-detected invasive breast cancers and 9,360 cases of
      screen-detected ductal carcinoma in situ were reported over the past 10 years.
      Among these cancers, there were 240 cases of untreated invasive breast cancer and
      239 cases of untreated ductal carcinoma in situ, among which zero were reported
      to have spontaneously disappeared or regressed at next mammography. CONCLUSIONS:
      Among 479 untreated breast cancers detected on screening mammography, none
      spontaneously disappeared or regressed. An unknown percentage of these cancers
      represent overdiagnosis, but because all untreated screen-detected cancers were
      visible and suspicious for malignancy at next mammographic examination, delaying
      the onset of screening or increasing the interval between screenings should not
      reduce the frequency of overdiagnosis.

PMID- 28457815
TI  - Reducing Inappropriate Use of Diagnostic Imaging Through the Choosing Wisely
      Initiative.

PMID- 28457816
TI  - Interventions to prevent stillbirth.
AB  - Stillbirth is one of the most distressing complications of pregnancy and still
      occurs far too frequently. The rate of stillbirth has been decreasing worldwide
      but room for improvement remains even in high-income countries. Risk factors for
      stillbirth have been identified in an effort to detect those women at increased
      risk. However, risk factors are non-specific and do not identify most
      stillbirths. Strategies employed to screen the general population such as
      assessment of fetal activity, fetal growth screening and biomarkers have also
      been used to identify increased risk for stillbirth. As with clinical risk
      factors, these methods are non-specific. Interventions to prevent stillbirth
      include antenatal testing of high-risk women, ultrasonographic assessments of
      fetal growth and Doppler velocimetry as well as iatrogenic preterm or term
      delivery. Additional research into the role of these interventions and better
      identification of those at high risk for stillbirth will help to achieve further
      stillbirth reduction.

PMID- 28457817
TI  - [Comparison of survival and chronic gastrointestinal toxicities in patients with
      locally advanced cervical cancer, treated by conventional or intensity-modulated
      radiation technique].
AB  - PURPOSE: To evaluate prospectively chronic gastrointestinal toxicity in patients
      with cervical cancer treated with conventional irradiation or with intensity
      modulated irradiation (IMRT). PATIENTS AND METHODS: Between June 2005 and
      September 2013, 109 patients underwent external radiotherapy followed by
      brachytherapy for cervical cancer at the "Institut de Cancerologie de Lorraine".
      Each patient receiving IMRT was paired with a patient receiving conventional
      radiotherapy on the following criteria: concomitant chemotherapy, additional
      nodal dose, treatment of para-aortic lymph node area, age. The toxicity
      collection was prospective using the RTOG scale. The main objective was to
      compare the incidence of gastrointestinal toxicity chronic between the two
      groups. In a second time, the influence of dosimetric parameters on chronic GI
      toxicity was investigated. Comparisons of acute toxicity, chronic genitourinary
      toxicities, overall survival, disease-free survival were secondary objectives.
      RESULTS: Sixty-six patients were able to be matched. Overall survival at 36
      months was 71% in the conventional radiotherapy group against 73% in the IMRT
      group (P=0.54). There was no significant difference between the two groups in
      terms of digestive chronic toxicity (P=0.17), nor in terms acute gastrointestinal
      toxicities (P=0.6445) and genitourinary (P=0.5724). IMRT spared significantly
      small bowel (P=0.0006) and rectum (P=0.0046) from 30Gy dose, and bladder from
      45Gy (P<0.001). The incidence of genitourinary toxicity was significantly
      different between the two groups (P=0.03) in favor of conventional radiotherapy.
      CONCLUSION: Our study does not seem to show significant difference in the
      occurrence of chronic gastrointestinal toxicities between the two groups.
      Clinical efficacy seems comparable. Larger studies with longer follow-up period
      should be conducted.

PMID- 28457818
TI  - Opioid neurotransmission modulates defensive behavior and fear-induced
      antinociception in dangerous environments.
AB  - The effects of endogenous opioid peptide antagonists on panic-related responses
      are controversial. Using elevated mazes and a prey-versus-predator paradigm, we
      investigated the involvement of the endogenous opioid peptide-mediated system in
      the modulation of anxiety- and panic attack-induced responses and innate fear
      induced antinociception in the present work. Wistar rats were intraperitoneally
      pretreated with either physiological saline or naloxone at different doses and
      were subjected to either the elevated plus- or T-maze test or confronted by
      Crotalus durissus terrificus. The defensive behaviors of the rats were recorded
      in the presence of the predator and at 24h after the confrontation, when the
      animals were placed in the experimental enclosure without the rattlesnake. The
      peripheral non-specific blockade of opioid receptors had a clear anxiolytic-like
      effect on the rats subjected to the elevated plus-maze but not on those subjected
      to the elevated T-maze; however, a clear panicolytic-like effect was observed,
      i.e., the defensive behaviors decreased, and the prey-versus-predator interaction
      responses evoked by the presence of the rattlesnakes increased. A similar effect
      was noted when the rats were exposed to the experimental context in the absence
      of the venomous snake. After completing all tests, the naloxone-treated groups
      exhibited less anxiety/fear-induced antinociception than the control group, as
      measured by the tail-flick test. These findings demonstrate the anxiolytic and
      panicolytic-like effects of opioid receptor blockade. In addition, the
      fearlessness behavior displayed by preys treated with naloxone at higher doses
      enhanced the defensive behavioral responses of venomous snakes.

PMID- 28457819
TI  - Mechanisms underlying alterations in norepinephrine levels in the locus coeruleus
      of ovariectomized rats: Modulation by estradiol valerate and black cohosh.
AB  - Hot flushes are common in menopause. Norepinephrine (NE), primarily synthesized
      in the locus coeruleus (LC), plays a major role in central thermoregulation.
      Furthermore, we previously observed decreased dopamine beta hydroxylase (DbetaH),
      a key enzyme in NE synthesis, in LC neurons following ovariectomy. In this study,
      we explore the mechanisms underlying decreased NE levels in the LC (LC-NE) in
      ovariectomized (OVX) rats, and the modulating effects of estradiol valerate (E2)
      and black cohosh (ICR). We used high-performance liquid chromatography to detect
      LC-NE in SHAM, OVX, OVX-E2, and OVX-ICR groups. Western blotting and
      immunohistochemistry were performed to investigate the expression of NE metabolic
      enzymes, the NE reuptake transporter (NET), and estrogen receptors (ERs) in the
      LC. We observed significant LC-NE decreases in the OVX group. E2 and ICR enhanced
      LC-NE but did not restore them to SHAM levels. Ovariectomy affected NE synthesis,
      degradation, and reuptake. Levels of NE catabolic enzymes monoamine oxidase A
      (MAOA) and catechol-O-methyltransferase (COMT) decreased, while NET expression
      increased. E2 restored MAOA and COMT to SHAM levels but had no effect on NET. ICR
      restored COMT and NET to SHAM levels but had no effect on MAOA. Moreover, the OVX
      group also exhibited decreased expression of ERalpha and ERbeta. E2 enhanced the
      expression of ERalpha and ERbeta, while ICR only enhanced ERbetaexpression. Taken
      together, reduced NE in OVX rats resulted from reduced synthesis and increased
      degradation and reuptake. E2 and ICR may regulate these processes in different
      ways through various ERs.

PMID- 28457820
TI  - Differential roles for Akt and mTORC1 in the hypertrophy of Pten mutant neurons,
      a cellular model of brain overgrowth disorders.
AB  - Mutations in the PI3K/Akt/mTOR signaling pathway or in the upstream negative
      regulator Pten cause human brain overgrowth disorders, such as focal cortical
      dysplasia and megalencephaly, and are characterized by the presence of
      hypertrophic neurons. These disorders often have a pediatric onset and a high
      comorbidity with drug-resistant epilepsy; however, effective pharmacological
      treatments are lacking. We established forebrain excitatory neuron-specific Pten
      deficient cultures as an in vitro model of brain overgrowth disorders, and
      investigated the effects of this Pten mutation on PI3K/Akt/mTOR signaling and
      neuronal growth. Mutant neurons exhibit excessive PI3K/Akt/mTOR signaling
      activity, enlarged somas and increased dendritic arborization. To understand the
      contributions of Akt and mTORC1 kinases to the hypertrophy phenotype, we
      evaluated the effects of short-term treatment with the Akt inhibitor MK-2206, and
      the mTORC1 inhibitor RAD001, which have shown safety and efficacy in human cancer
      clinical trials. We found that RAD001 treatment only partially reversed the
      morphological abnormalities of Pten mutant neurons, whereas MK-2206 treatment
      completely rescued the phenotype. Interestingly, neither treatment altered the
      size or morphology of normal neurons. Our results suggest that Akt is a major
      determinant of neuronal growth, and that Akt inhibition may be an effective
      strategy for pharmacological intervention in brain overgrowth disorders.

PMID- 28457821
TI  - A retrospective study of the characterization of Rickettsia species in ticks
      collected from humans.
AB  - Rickettsiae (family Rickettsiaceae, order Rickettsiales) are obligate
      intracellular bacteria transmitted by arthropod vectors. Several Rickettsia
      species causing vector-borne rickettsioses belong to the spotted fever group
      (SFG). Traditionally, Rickettsia conorii has been considered as the main
      etiologic agent of Mediterranean spotted fever. However, the molecular
      characterization of rickettsiae allowed identifying other species involved in
      spotted fever in the Mediterranean region. In this study, 42 ticks collected from
      humans were subjected to morphological identification and molecular
      characterization of Rickettsia species potentially involved in human
      rickettsiosis in Sicily. Fourteen ticks positive to at least two Rickettsia spp.
      molecular markers were used in the study. Identified Rickettsia spp. included R.
      conorii, found in Rhipicephalus sanguineus sensu lato and Rhipicephalus
      turanicus, Rickettsia aeschlimannii found in Hyalomma marginatum, Hyalomma
      lusitanicum, Dermacentor marginatus and Ixodes ricinus, Rickettsia massiliae
      found in R. turanicus and R. sanguineus s.l., and Rickettsia slovaca found in D.
      marginatus and R. sanguineus s.l. Our results showed a great variety of zoonotic
      Rickettsia spp. in ticks collected from humans in Sicily. The Rickettsia spp.
      reported in this study were identified in previously recognized or new potential
      tick vectors in Europe, highlighting the risk of infection by different
      Rickettsia spp. for humans bitten by ticks in Sicily.

PMID- 28457822
TI  - Assessment of a quantitative 5' nuclease real-time polymerase chain reaction
      using groEL gene for Ehrlichia and Anaplasma species in rodents in Brazil.
AB  - New genotypes of Anaplasmataceae agents have been detected in wild carnivores,
      birds and deer in Brazil. The present work aimed to investigate the presence of
      Ehrlichia and Anaplasma species in rodents sampled in Brazil. Additionally, a
      newly designed quantitative 5' nuclease real-time multiplex PCR for Ehrlichia and
      Anaplasma spp. detection based on groEL gene amplification was designed, showing
      high specificity and sensitivity (10 groEL fragment copy/MUL). Between 2000 and
      2011, different rodent species [n=60] were trapped in 5 Brazilian biomes. Among
      458 rodent spleen samples, 0.4% (2/458) and 2.4% (11/458) were positive for
      Ehrlichia and Anaplasma spp., respectively. Of 458 samples, 2.0% (9/458) and 1.1%
      (5/458) were positive for Anaplasma sp. and Ehrlichia sp., respectively, using
      conventional 16S rRNA PCR assays. Maximum Likelihood phylogenetic analyse based
      on a small region of 16S rRNA genes positioned the Anaplasma genotypes in rodents
      near Anaplasma phagocytophilum or Anaplasma marginale and Anaplasma odocoilei
      isolates. Ehrlichia genotypes were closely related to E. canis. There was a low
      occurrence of Anaplasma and Ehrlichia in wild and synanthropic rodents in Brazil,
      suggesting the circulation of new genotypes of these agents in rodents in the
      studied areas.

PMID- 28457823
TI  - Dibenzocyclooctadiene lignans from Kadsura heteroclita.
AB  - Sixteen dibenzocyclooctadiene lignans, including eight new ones, kadheterins A-H
      (1-8), and a new natural product, 9-benzoyloxy-gomisin B (9), were isolated from
      the stems of K. heteroclita. The structures of 1-9 were elucidated by extensive
      spectroscopic methods, and their absolute configurations were determined by
      combining CD with ROESY experiments. Additionally, the absolute configuration of
      1 was further confirmed by single crystal X-ray crystallographic analysis. In
      vitro activity assays showed that 1 exhibited moderate cytotoxicity against HL-60
      with IC50 value at 14.59MUM.

PMID- 28457824
TI  - Surgical correction of mandibular hypoplasia in hemifacial microsomia: A
      retrospective study in 39 patients.
AB  - PURPOSE: Repair of the mandibular deformity in hemifacial microsomia (HFM)
      remains controversial, and there is scant information in the literature regarding
      the late outcomes. The aim of this study was to evaluate architectural and
      aesthetic long-term outcomes for primary mandibular surgery in patients with HFM.
      MATERIALS AND METHODS: Thirty-nine patients with types II and type III HFM were
      included in this retrospective study. Depending on the nature of the mandibular
      deformity, patients were treated using a costochondral graft (CCG) or a vertical
      ramus osteotomy (VRO). Architectural and aesthetic parameters were evaluated
      preoperatively, postoperatively, and at the end of the follow-up period. RESULTS:
      The architectural analysis revealed the restoration of a level occlusal canting
      at the end of the follow-up period (p < 0.0001); the chin deviation was corrected
      immediately by the surgery, although a trend to recurrence was noted at the last
      follow-up evaluation (p < 0.0001). The aesthetic assessment revealed a
      significant improvement of the chin deflection, and correction of the lip
      commissural line tilt (p < 0.0001). Twenty-three percent of the patients required
      an additional orthognathic revision. CONCLUSION: CCG and VRO continue to be
      suitable and safe procedures with good outcomes that allow a single-stage
      correction of occlusion and preservation of mandibular growth in young patients
      with type II and type III HFM.

PMID- 28457825
TI  - Osteosynthesis of partial rib osteotomy in a miniature pig model using human
      standard-sized magnesium plate/screw systems: Effect of cyclic deformation on
      implant integrity and bone healing.
AB  - Magnesium alloys are candidates for resorbable material in bone fixation.
      However, the degradation and performance of osteosynthesis plate/screw systems in
      vivo, under cyclic deformation, is unknown. We evaluated the outcomes of human
      standard-sized magnesium plate/screw systems with or without plasma-electrolytic
      surface modifications in a miniature pig rib model. Of a total of 14 minipigs,
      six were implanted with coated magnesium WE43 six-hole plates/screws, six
      received magnesium uncoated plates/screws, and two received titanium
      osteosynthesis systems. The performance of the plate/screw fixation system on
      partially osteotomized 7th ribs was compared with that on intact 9th ribs.
      Radiological examinations were performed in vivo at 1, 4 and 8 weeks and after
      euthanasia at 12 and 24 weeks. After euthanasia the bone blocks were analyzed by
      computed tomography (CT), microfocus computed tomography (micro-CT), histology
      and histomorphometry. Follow-up post-surgery showed no trouble with wound
      healing. In vivo radiological examinations showed higher amounts of gas formation
      above the uncoated magnesium plates fixed on the partially osteotomized and
      intact ribs. CT scans showed no broken plates or implant displacement. The micro
      CT examination demonstrated better surrounding bone properties around the coated
      than the uncoated magnesium implants 12 weeks after surgery. No negative
      influence of magnesium degradation on bone healing was observed with histological
      examinations. Plastic deformation during surgery and cyclic deformation did not
      affect the integrity of the used magnesium plates. This study showed promising
      results for the further development of coated magnesium plate/screw systems for
      bone fixation.

PMID- 28457826
TI  - The clinical implications of severe low rib fracture in the management of
      diaphragm injury: A Case Control Study.
AB  - BACKGROUND: The objective of this study was to analyze the differences in
      clinical presentation and characteristics with regard to diaphragmatic injury
      between blunt trauma patients with severe low rib fractures and those without
      severe low rib fractures. METHODS: The medical records of all patients with
      diaphragmatic injuries who were surgically treated at this level I trauma center,
      between January 2004 and December 2016 were reviewed. Patient notes, radiologic
      findings, and operative reports were evaluated. All of the diaphragmatic injuries
      were confirmed based on the operative findings. Rib fracture with displacement
      between the ends of the fracture of more than half the width of the fractured rib
      on computed tomography was classified as 'severe rib fracture'. Patients were
      categorized into 2 groups and analyzed: those who had more than one severe rib
      fracture in low ribs on the ipsilateral side of the diaphragm injury (Severe
      group), and those with no severe rib fracture (Non-severe group). RESULTS:
      Delayed diagnosis of diaphragmatic injury was more frequent in the Severe group
      than in the Non-severe group (81.8% vs 36.8%, p-value = 0.026). With regard to
      initial indications for operation, intrathoracic visceral herniation was more
      frequent in the Non-severe group (78.9% vs 18.2%, p-value = 0.002), while
      hemothorax was more frequent in the Severe group (63.6% vs 5.3%, p-value =
      0.001). Central type diaphragmatic laceration was more frequent in the Non-severe
      group than in the Severe group (78.9% vs 18.2%, p-value = 0.002). The diameter of
      diaphragmatic injury was larger in the Non-severe group than in the Severe group
      (9.70 +/- 4.10 cm vs 4.80 +/- 3.60 cm, p-value = 0.004). CONCLUSION: The results
      of this study imply that a low threshold for thoracotomy or laparotomy should be
      considered in blunt trauma patients with severe low rib fractures for the purpose
      of hidden diaphragmatic injury detection and management.

PMID- 28457827
TI  - Ventilation distribution assessed with electrical impedance tomography and the
      influence of tidal volume, recruitment and positive end-expiratory pressure in
      isoflurane-anesthetized dogs.
AB  - OBJECTIVE: To examine the intrapulmonary gas distribution of low and high tidal
      volumes (VT) and to investigate whether this is altered by an alveolar
      recruitment maneuver (ARM) and 5 cmH2O positive end-expiratory pressure (PEEP)
      during anesthesia. STUDY DESIGN: Prospective randomized clinical study. ANIMALS:
      Fourteen client-owned bitches weighing 26 +/- 7 kg undergoing elective
      ovariohysterectomy. METHODS: Isoflurane-anesthetized dogs in dorsal recumbency
      were ventilated with 0 cmH2O PEEP and pressure-controlled ventilation by
      adjusting the peak inspiratory pressure (PIP) to achieve a low (7 mL kg-1; n = 7)
      or a high (12 mL kg-1; n = 7) VT. Ninety minutes after induction (T90), an ARM
      (PIP 20 cmH2O for 10 seconds, twice with a 10 second interval) was performed
      followed by the application of 5 cmH2O PEEP for 35 minutes (RM35). The vertical
      (ventral=0%; dorsal=100%) and horizontal (right=0%; left=100%) center of
      ventilation (CoV), four regions of interest (ROI) (ventral, central-ventral,
      central-dorsal, dorsal) identified in electrical impedance tomography images, and
      cardiopulmonary data were analyzed using two-way repeated measures anova.
      RESULTS: The low VT was centered in more ventral (nondependent) areas compared
      with high VT at T90 (CoV: 38.8 +/- 2.5% versus 44.6 +/- 7.2%; p = 0.0325). The
      ARM and PEEP shifted the CoV towards dorsal (dependent) areas only during high VT
      (50.5 +/- 7.9% versus 41.1 +/- 2.8% during low VT, p = 0.0108), which was more
      distributed to the central-dorsal ROI compared with low VT (p = 0.0046). The
      horizontal CoV was centrally distributed and cardiovascular variables remained
      unchanged throughout regardless of the VT, ARM, and PEEP. CONCLUSIONS AND
      CLINICAL RELEVANCE: Both low and high VT were poorly distributed to dorsal
      dependent regions, where ventilation was improved following the current ARM and
      PEEP only during high VT. Studies on the role of high VT on pulmonary
      complications are required.

PMID- 28457828
TI  - Skin lesions following pregabalin administration in a cat.

PMID- 28457829
TI  - The number of visits and blood pressure measurements influence the prevalence of
      high blood pressure in adolescents.
AB  - The aim of this study was to analyze the influence of the number of visits and
      the number of blood pressure (BP) measurements on the prevalence of high blood
      pressure (HBP) in adolescents. A cross-sectional epidemiologic study with 481
      adolescents (14-19 years old) selected using a random cluster sampling strategy.
      We measured the BP three times in a first visit. Adolescents with HBP performed
      subsequent visits. The final calculation of BP followed four strategies: the 1st
      measure, mean of 1st and 2nd measurements, mean of all three measurements, and
      averaging the 2nd and 3rd measurements. The prevalence of HBP in the first and
      second visits was 6.4% and 1.9%, and the prevalence of hypertension (after three
      visits) was 1.7%. The prevalence of HBP varied from 8.6%-18.6% for boys and 4.6%
      9.2% for girls, using the average 2nd and 3rd measurements and the 1st
      measurement, respectively. In all strategies, HBP and hypertension were more
      prevalent in boys and students attending the nocturnal shift. The number of
      visits and number of measurements affect the prevalence of HBP and hypertension
      in adolescents. Thus, clinicians and researchers should consider these aspects
      when assessing BP in adolescents aged 14-19 years old.

PMID- 28457830
TI  - Prevalence and risk factors for hepatitis B and C viruses in patients with
      leprosy.
AB  - It has been reported a higher seroprevalence of HBV and HCV in leprosy patients
      than in the general population, but the reasons for these findings are not yet
      clear. On the other hand, there is evidence that these viruses may influence the
      onset of leprosy reactional episodes, an important cause of neurological
      sequelae. This study aimed to determine seroprevalence and risk factors for HBV
      and HCV in leprosy patients and to investigate its association with leprosy
      reactions. Patients attended from 2015 to 2016 at a Reference Center in Leprosy
      in Northeastern region of Brazil, were interviewed, had their records reviewed to
      investigate biological, clinical, behavioral and socioeconomic factors, and
      underwent blood sample collection. Biological samples were tested for HBV (HBsAg,
      anti-HBs and anti-HBs) and HCV (anti-HCV) serological markers by ELISA and, in
      anti-HCV positive samples, HCV RNA was screened by real time PCR. SPSS program
      was used to analyze the data. A total of 403 leprosy patients were included.
      Although anti-HBc was positive in 14.1%, there was no detection of HBsAg, which
      contradicts the hypothesis that leprosy patients have immune deficit that make
      them more prone to chronic HBV infection. Multibacillary leprosy (0.057), health
      related work (0.011) and lower educational level (0.035) were associated with
      anti-HBc positivity. Anti-HCV was positive in 0.5%, with no detection of HCV RNA.
      No association was identified between anti-HCV and the epidemiological analyzed
      factors. There was also no association of anti-HBc or anti-HCV with type 1 or
      type 2 leprosy reactions. Thus, the seroprevalence of HBV and HCV in leprosy
      patients was similar to that of the general population of Northeastern region of
      Brazil, and no association of HBV or HCV with leprosy reactions was observed.

PMID- 28457831
TI  - Pursuing Novel Ideas-Confessions of Lost Opportunities!

PMID- 28457832
TI  - Indocyanine Green Angiography-assisted Laparoendoscopic Single-site
      Varicocelectomy.
AB  - OBJECTIVE: To study the efficacy of a new laparoscopic varicocelectomy technique
      using indocyanine green (ICG) angiography. METHODS: Laparoendoscopic single-site
      (LESS) varicocelectomy using ICG angiography was performed in a single
      institution on 11 patients with a grade 2 or 3 varicocele. Adult men (N = 9, 82%)
      who were apparently infertile and had a varicocele, as well as prepubertal boys
      (N = 2, 18%) with testicular growth retardation, underwent a LESS varicocelectomy
      using ICG angiography. After the separation of testicular veins, arteries, and
      lymphatics, ICG was injected intravenously, and arterial and venous blood flows
      were observed by ICG fluorescence. Spermatic veins were cauterized by bipolar
      forceps and cut. The spermatic artery and lymphatics were preserved. RESULTS: The
      mean time to the arterial phase (AP) from the ICG injection was 34.9 seconds and
      the mean time to the venous phase was 58.3 seconds. The mean interval from the
      arterial phase to the venous phase was 23.3 seconds, and in all cases, this time
      interval facilitated the identification of arteries and veins. The rates of
      residual varicocele 3 and 6 months after surgery were 9.1% and 0%, respectively.
      Serious postoperative complications were not observed nor were adverse events
      induced by ICG. CONCLUSION: ICG angiography appears to be safe and appears to
      facilitate the detection of artery and veins during LESS varicocelectomy.
      Continuing investigations of efficacy are required of this new and promising
      procedure in a larger number of patients.

PMID- 28457833
TI  - Evolution of Surgical Professional Organizations: A Case Study of Thomas Moore,
      Graceland, and the American Urological Association.

PMID- 28457834
TI  - A network perspective on antimicrobial peptide combination therapies: the
      potential of colistin, polymyxin B and nisin.
AB  - Antimicrobial combinations involving antimicrobial peptides (AMPs) attract
      considerable attention within current antimicrobial and anti-resistance research.
      The objective of this study was to review the available scientific literature on
      the effects of antimicrobial combinations involving colistin (polymyxin E),
      polymyxin B and nisin, which are US Food and Drug Administration (FDA)-approved
      AMPs broadly tested against prominent multidrug-resistant pathogens. A
      bioinformatics approach based on literature mining and manual expert curation
      supported the reconstruction of experimental evidence on the potential of these
      AMP combinations, as described in the literature. Network analysis enabled
      further characterisation of the retrieved antimicrobial agents, targets and
      combinatory effects. This systematic analysis was able to output valuable
      information on the studies conducted on colistin, polymyxin B and nisin
      combinations. The reconstructed networks enable the traversal and browsing of a
      large number of agent combinations, providing comprehensive details on the
      organisms, modes of growth and methodologies used in the studies. Therefore,
      network analysis enables a bird's-eye view of current research trends as well as
      in-depth analysis of specific drugs, organisms and combinatory effects, according
      to particular user interests. The reconstructed knowledge networks are publicly
      accessible at http://sing-group.org/antimicrobialCombination/. Hopefully, this
      resource will help researchers to look into antimicrobial combinations more
      easily and systematically. User-customised queries may help identify missing and
      less studied links and to generate new research hypotheses.

PMID- 28457835
TI  - In vitro activity of a novel compound, Mul-1867, against clinically significant
      fungi Candida spp. and Aspergillus spp.
AB  - There is an urgent need for new antifungal compounds to treat various types of
      fungal infections, including pulmonary infections. This study was designed to
      investigate the potency of a novel compound (Mul-1867) against Candida spp. and
      Aspergillus spp. isolated from patients with fungal pneumonia, cystic fibrosis
      and chronic obstructive pulmonary disease. Mul-1867 was highly effective against
      susceptible control strains as well as resistant clinical isolates, with minimum
      fungicidal concentrations (MFCs) varying from 0.06 ug/mL to 0.5 ug/mL. It was
      also highly effective against pre-formed 48-h-old biofilms formed by yeasts and
      moulds. The half-minimal biofilm eradication concentration (MBEC50) was equal to
      the MFC. The minimum biofilm eradication concentration to eliminate 90% of
      biofilms (MBEC90) varied from 1 * to 4 * MFC. Scanning electron microscopy
      revealed morphological changes accompanied by the release of intracellular
      material from the fungal cells following exposure to Mul-1867. Furthermore, an
      increased concentration of nucleic acids was found in the medium after 5 min and
      20 min of Mul-1867 treatment, indicating leakage of cytoplasmic contents.
      Overall, these data indicate that Mul-1867 may be a promising inhaled antifungal
      agent for the treatment and prevention of fungal respiratory infections.

PMID- 28457838
TI  - Reply by Authors.

PMID- 28457837
TI  - Cost-effectiveness of deep brain stimulation versus treatment as usual for
      obsessive-compulsive disorder.
AB  - BACKGROUND: Deep Brain Stimulation (DBS) is effective for obsessive-compulsive
      disorder (OCD), but requires expensive medical procedures. To date, no study has
      examined the cost-effectiveness of DBS for OCD. OBJECTIVE: To perform the first
      economic evaluation of DBS for therapy refractory OCD. METHODS: We conducted a 2
      year prospective, open cost-effectiveness study, comparing DBS (n = 17) with
      treatment as usual (TAU) (n = 11), with cost per Quality-Adjusted-Life-Year
      (QALY) as outcome measure. Apart from the base-case, or primary analysis, we
      conducted two practice-based scenarios: (1) standard care scenario, without
      research and innovation costs, and (2) rechargeable scenario, in which we assume
      the use of a rechargeable battery. Base-case and both scenarios were extrapolated
      to four years to estimate long-term cost-effectiveness. RESULTS: Compared to TAU,
      DBS provides an additional 0.26 QALY (SD = 0.16). Median cost per QALY gained is
      estimated at ?141,446 for base-case, ?115,916 for standard care and ?65,394 for
      the rechargeable scenario. Extending the time-horizon to four years results in a
      median cost per QALY of ?80,313 for base-case, ?69,287 for standard care, and
      turned out to be cost-saving at ?4678 per QALY for the rechargeable scenario.
      Assuming a willingness to pay threshold of ?80,000/QALY, DBS, under base-case and
      standard care had 25% and 35% probability of being more cost-effective than TAU.
      With the rechargeable scenario and in all scenarios extrapolated to four years,
      the probability of cost-effectiveness was equal or higher than TAU. CONCLUSIONS:
      This study indicates DBS for OCD is cost-effective in the long-term, especially
      when rechargeable batteries are taken into account.

PMID- 28457836
TI  - Imaging of current flow in the human head during transcranial electrical therapy.
AB  - BACKGROUND: It has been assumed that effects caused by tDCS or tACS
      neuromodulation are due to electric current flow within brain structures.
      However, to date, direct current density distributions in the brains of human
      subjects have not been measured. Instead computational models of tDCS or tACS
      have been used to predict electric current and field distributions for dosimetry
      and mechanism analysis purposes. OBJECTIVE/HYPOTHESIS: We present the first in
      vivo images of electric current density distributions within the brain in four
      subjects undergoing transcranial electrical stimulation. METHODS: Magnetic
      resonance electrical impedance tomography (MREIT) techniques encode current flow
      in phase images. In four human subjects, we used MREIT to measure magnetic flux
      density distributions caused by tACS currents, and then calculated current
      density distributions from these data. Computational models of magnetic flux and
      current distribution, constructed using contemporaneously collected T1-weighted
      structural MRI images, were co-registered to compare predicted and experimental
      results. RESULTS: We found consistency between experimental and simulated
      magnetic flux and current density distributions using transtemporal (T7-T8) and
      anterior-posterior (Fpz-Oz) electrode montages, and also differences that may
      indicate a need to improve models to better interpret experimental results. While
      human subject data agreed with computational model predictions in overall scale,
      differences may result from factors such as effective electrode surface area and
      conductivities assumed in models. CONCLUSIONS: We believe this method may be
      useful in improving reproducibility, assessing safety, and ultimately aiding
      understanding of mechanisms of action in electrical and magnetic neuromodulation
      modalities.

PMID- 28457839
TI  - Editorial Comment.

PMID- 28457840
TI  - Reply by Authors.

PMID- 28457841
TI  - Editorial Comment.

PMID- 28457842
TI  - Editorial Comment.

PMID- 28457844
TI  - Reply by Authors.

PMID- 28457843
TI  - Re: Properties of the 4-Kallikrein Panel Outside the Diagnostic Gray Zone: Meta
      Analysis of Patients with Positive Digital Rectal Examination or Prostate
      Specific Antigen 10 ng/ml and Above: A. Vickers, E. A. Vertosick, D. D. Sjoberg,
      M. J. Roobol, F. Hamdy, D. Neal, A. Bjartell, J. Hugosson, J. L. Donovan, A.
      Villers, S. Zappala and H. Lilja J Urol 2017;197:607-613.

PMID- 28457845
TI  - The evolution of lipidomics through space and time.
AB  - Although the foundations of mass spectrometry-based lipidomics have been
      practiced for over 30 years, recent technological advances in ionization
      modalities in conjunction with robust increases in mass accuracy and resolution
      have greatly accelerated the emergence, growth and importance of the field of
      lipidomics. Moreover, advances in the separation sciences, bioinformatic
      strategies and the availability of robust databases have been synergistically
      integrated into modern lipidomic technologies leading to unprecedented
      improvements in the depth, penetrance and precision of lipidomic analyses and
      identification of their biological and mechanistic significance. The purpose of
      this "opinion" article is to briefly review the evolution of lipidomics, critique
      the platforms that have evolved and identify areas that are likely to emerge in
      the years to come. Through seamlessly integrating a rich repertoire of mass
      spectrometric, chemical and bioinformatic strategies, the chemical identities and
      quantities of tens of thousands to hundreds of thousands of different lipid
      molecular species and their metabolic alterations during physiologic or
      pathophysiologic perturbations can be obtained. Thus, the field of lipidomics
      which already has a distinguished history of exciting new discoveries in many
      disease states holds unparalleled potential to identify the pleiotropic roles of
      lipids in health and disease at the chemical level. This article is part of a
      Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp
      Kohlwein.